PMID- 15841778
TI  - Effect of bladder volume, gender and body position on the shape and position of
      the urinary bladder.
AB  - OBJECTIVE: The optimal design of bladder volume-monitoring equipment, e.g.
      regarding transducer design and software algorithms, depends greatly on the shape
      and position of the bladder or on potential changes due to body position and
      bladder volume. The purpose of this study was to study the influence of body
      position, bladder volume and gender on the shape and position of the bladder.
      MATERIAL AND METHODS: MRI scans of 11 young volunteers were performed during
      changes in posture. Images were recorded in the transverse and frontal planes and
      repeated four to six times through the bladder-filling cycle from empty to full.
      The position of the bladder midpoint was measured in the three planes. Moreover,
      to account for shape, the compactness of the cross-section of the bladder was
      calculated based on its perimeter and area. The effect of body position and
      gender was analyzed using repeated-measures ANOVA and the independent samples t
      test, respectively. RESULTS: No significant effect of body position on bladder
      position or shape was found. Gender was shown to have a significant impact on
      both the position and shape of the bladder: the female bladder was positioned
      more caudally and was less compact in the transverse plane than the male bladder.
      Furthermore, there was significant cranial-dorsal movement of the bladder during
      filling. CONCLUSION: No significant changes in the position or shape of the
      bladder were observed during changes in body position in young subjects,
      regardless of bladder volume or gender. However, changes in both parameters were
      found due to bladder filling.

PMID- 15841779
TI  - Voiding position does not affect uroflowmetric parameters and post-void residual
      urine volume in healthy volunteers.
AB  - OBJECTIVE: To investigate the effect of voiding position using uroflowmetry and
      post-void residual (PVR) urine volume assessment in healthy men and women.
      MATERIAL AND METHODS: The study population comprised 72 healthy volunteers. The
      mean (range) ages of the male (n = 36) and female (n = 36) subjects were 30 (18
      40) years and 32 (21-44) years, respectively. The uroflowmetric studies were
      repeated in the standing, sitting and crouching positions for men and in the
      sitting and crouching positions for women. At least three measurements were
      obtained for all voiding positions for each volunteer. PVR volumes were measured
      using trans-abdominal ultrasound after each voiding. Maximum flow rate (Qmax),
      average flow rate (Qave), voided volume (VV) and PVR values obtained in each
      voiding position were compared with those obtained in the other positions.
      Comparisons were done using one-way ANOVA. RESULTS: The mean Qmax and Qave values
      obtained in the sitting, crouching and standing positions in men were 24.29 +/-
      0.73 and 15.67 +/- 0.37, 23.28 +/- 0.64 and 15.56 +/- 0.33, and 23.58 +/- 0.63
      and 15.81 +/- 0.34 ml/s, respectively. The mean VV and PVR values obtained in the
      sitting, crouching and standing positions in men were 297.5 +/- 12.71 and 13.52
      +/- 1.02, 306.3 +/- 13.46 and 14.02 +/- 1.08, and 309.9 +/- 13.14 and 12.92 +/-
      0.95 ml, respectively. In women, the mean Qmax and Qave values obtained in the
      sitting and crouching positions were 28.09 +/- 0.66 and 18.26 +/- 0.36, and 27.98
      +/- 0.59 and 17.31 +/- 0.35 ml/s, respectively. The mean VV and PVR values
      obtained in the sitting and crouching positions in women were 331.8 +/- 13.28 and
      11.82 +/- 0.99, and 326.9 +/- 12.87 and 12.79 +/- 1.07 ml, respectively. There
      were no significant differences in any of the parameters between voiding
      positions in either group. CONCLUSION: Urinary flow rates and PVR urine volume do
      not seem to be affected by voiding position in healthy men and women.

PMID- 15841780
TI  - Retropubic transvesical prostatectomy for significant prostatic enlargement must
      remain a standard part of urology training.
AB  - OBJECTIVE: In recent years, open prostatectomy for benign enlargement has again
      become an issue of interest. We evaluated our experience with this procedure.
      Special attention was paid to the effect of the experience of the surgeon on
      operative outcome. MATERIAL AND METHODS: The patient files of 201 patients were
      evaluated retrospectively for operation outcome parameters. Statistical analysis
      was performed where appropriate. The different parameters were also analyzed
      separately for patients operated on by the head of the department and those
      operated on by residents. RESULTS: We found significant differences in pre- and
      postoperative median residual urine volume (85 vs 0.0 ml; p < 0.001) and pre- and
      postoperative median urinary flow (6.0 vs 20.8 ml/s; p < 0.001). There was a
      moderate correlation between preoperative determination of the prostate volume by
      means of transrectal ultrasound and postoperative histological weight. Patients
      operated on by the head of the department had a significantly shorter operation
      time. Postoperative complications were rarely seen in either group. The rates of
      postoperative complications were as follows: permanent incontinence, 0.5%;
      endoscopic revision (bleeding), 3%; open revision, 1%; urinary tract infection,
      13%; and secondary wound healing, 5.5%. CONCLUSIONS: We feel that open
      prostatectomy remains an excellent technique for large prostate adenomas and
      should always be offered in such cases as a true alternative to endoscopic
      techniques. Having a well-trained urologist perform the procedure is the best
      guarantee of minimal blood loss and minimal complication rates. Therefore, open
      prostatectomy should be part of the education program of all prostate centers and
      urological departments.

PMID- 15841781
TI  - Patient tolerance during outpatient flexible cystoscopy--a prospective,
      randomized, double-blind study comparing plain lubrication and lidocaine gel.
AB  - OBJECTIVE: To compare the tolerance of flexible cystoscopy with topical
      anesthetic versus simple lubrication when the assigned lubricant is instilled 5
      min before the exploration. MATERIAL AND METHODS: A total of 185 consecutive
      patients were randomly assigned either to simple lubrication (Group 1) or to
      lidocaine hydrochloride gel (Group 2). Thirteen patients had some kind of
      difficulty during exploration (stenosis) that required additional manipulation or
      electrocoagulation for small relapses and were excluded from the final analysis,
      leaving 172 patients suitable for inclusion. After the intervention, all patients
      were surveyed regarding their discomfort and pain levels using a verbal scale and
      a visual analog scale ranging from zero to 10. A chi2 analysis was performed for
      comparison of qualitative covariables, and quantitative covariables were compared
      using Student's t-test. RESULTS: The 172 patients were evenly distributed between
      the two groups. Of those in Group 1, 89% noted little or no discomfort, compared
      to 84% in Group 2. Some pain or intense pain was noted by 10% and 16% in Groups 1
      and 2, respectively (p > 0.05). The average value on the visual analog scale was
      2.10 and 1.97 in Groups 1 and 2, respectively (p > 0.05). CONCLUSION: There are
      no differences in the perception of discomfort and pain by patients when
      anesthetic lubricant or simple lubrication are used if the waiting time before
      the exploration is 5 min.

PMID- 15841782
TI  - Rupture of papillary renal cell carcinoma.
AB  - OBJECTIVE: Typical signs of papillary renal cell carcinoma (PRCC) are extensive
      necroses of the tumorous mass, which can modify the clinical appearance of PRCC.
      These necroses can imitate cysts on radiological examinations (ultrasonography
      and CT). The tumours are fragile and vulnerable to spontaneous rupture or rupture
      following minimal trauma (i.e. they act as a locus minoris resistentiae).
      MATERIAL AND METHODS: A total of 650 patients with a total of 671 renal tumours
      were surgically treated at our hospital between January 1991 and December 2003.
      RESULTS: In 16 cases bilateral tumours were found (in all cases RCC) and in five
      cases two types of tumour were identified in one kidney [all were a combination
      of conventional RCC (CRCC) and PRCC]. Altogether, 621 tumours (92.5%) were
      diagnosed as RCCs. Of these, CRCC was found in 563 cases (90.7%), PRCC in 36
      (5.8%), chromophobe RCC in 14 (2.3%) and unclassified RCC in 7 (1.1%). All cases
      of ruptured PRCC were included in our study. Interestingly, only PRCCs ruptured
      in this series. Rupture was described in three cases of PRCC (8.3%): it was
      spontaneous in two cases and resulted from a traffic accident in the third.
      CONCLUSIONS: The extensive necrosis regularly found in PRCC can cause rupture of
      the tumour followed by retroperitoneal bleeding. Rupture affected <10% of our
      cases of PRCC. CT findings are usually not characteristic and can mimic a simple
      haematoma of unknown origin. Similarly, the perioperative finding is unclear in
      most cases. The final correct diagnosis of the renal tumour is frequently
      established only by the pathologist.

PMID- 15841783
TI  - Tumors in kidney fusion anomalies--report of five cases and review of the
      literature.
AB  - OBJECTIVE: Fusion anomalies of the kidney are rarely encountered and the
      association of malignant tumors with such conditions is exceedingly rare.
      Association of tumors with horseshoe kidney is also uncommon, with fewer than 200
      cases having been reported in the literature, and the association of tumors with
      crossed-fused ectopia is even rarer, with only four cases having been reported so
      far. MATERIAL AND METHODS: During the past decade five patients with fusion
      anomalies have been treated for tumors in our clinic, four of whom had horseshoe
      kidney and one of whom had crossed-fused left-to-right ectopia. The clinical,
      diagnostic and operative peculiarities of each case are presented and the recent
      literature on this topic is reviewed. RESULTS: Two patients were diagnosed with
      renal cell carcinoma, two had transitional cell carcinoma and one had oncocytoma.
      CONCLUSIONS: The commonest tumor reported in kidney fusion anomalies is renal
      cell carcinoma, although its reported incidence is no higher than that in the
      normal population. In the case of transitional cell carcinomas, diagnosis is
      usually made at an advanced stage. The value of thorough urologic and
      radiological investigations is stressed. Angiography, whether classical or in
      combination with multi-slice CT, is considered essential in order to confirm
      renal anomalies and the tumor situation and to plan the surgical approach. In our
      experience, radical nephrectomy with isthmus division via a transperitoneal
      approach is the treatment of choice.

PMID- 15841784
TI  - Informed consent for clinical education--randomized study of two different
      strategies at a urology surgery.
AB  - OBJECTIVE: To study whether or not the provision of written information in
      advance might influence patients' inclination to participate in the clinical
      education of medical students at a urology surgery. MATERIAL AND METHODS: A total
      of 169 outpatients referred to the urological surgery were randomly allocated
      either to receive information in advance or not, together with a notice of
      appointment that all patients receive by mail approximately 2 weeks prior to
      their visit. Patients in the experimental group received a written information
      letter in advance about medical education, whereas the control patients did not
      receive any written information, according to the standard procedure of the
      surgery. The patients were not told about the study until afterwards and neither
      the doctors/teachers nor the students knew in advance to which group a certain
      patient had been allocated. At the end of the visit the patients were asked to
      complete a questionnaire. RESULTS: The randomization procedure resulted in 83
      patients being informed in advance and 86 control patients not being informed.
      Forty-two patients completed the questionnaire: 19 in the experimental group and
      23 in the control group. There was no difference between the groups with regard
      to reasons for dropping out. CONCLUSIONS: This study indicates that the provision
      of information in advance does not negatively influence patients' inclination to
      participate in the clinical training of medical students.

PMID- 15841785
TI  - Botulinum toxin A for treatment of neurogenic detrusor overactivity and
      incontinence in patients with spinal cord lesions.
AB  - OBJECTIVE: To evaluate the efficacy of intravesical botulinum toxin A (BTA) in
      the treatment of severe neurogenic detrusor overactivity (NDO) with incontinence
      in patients with spinal cord lesions (SCLs). MATERIAL AND METHODS: Fifteen SCL
      patients suffering from NDO and incontinence were included in the study. The
      volume of urine leakage during episodes of incontinence was quantified, and
      filling cystometry was performed before and after BTA treatment. During BTA
      treatment, a total of 300 IU of BTA was injected cystoscopically into the
      detrusor muscle, excluding the trigone region. Antibiotic prophylaxis was given.
      RESULTS: Thirteen of 15 patients (87%) reported that they were fully continent
      after treatment and the volume of leakage in the two incontinent patients was
      significantly reduced. Anticholinergic medication was stopped in all patients
      after BTA treatment. Cystometry showed a marked reduction in pressures after
      treatment in all patients, with the maximum detrusor pressure during filling
      being significantly reduced (p < 0.0005) and the maximum volume at a detrusor
      pressure of <40 cmH2O being significantly increased (p < 0.0005) in all patients.
      The maximum bladder capacity was increased, although not significantly. The
      period during which the patients remained continent following treatment ranged
      from 4 to 12 months (median 7 months). With the exception of slight haematuria,
      which resolved spontaneously, no side-effects were observed, and no cases of
      autonomic hyperreflexia were seen during treatment. CONCLUSION: BTA proved to be
      a highly effective treatment modality for NDO and incontinence in SCL patients.
      Treatment was easy to perform and the duration of effect was acceptable.
      Furthermore, BTA treatment was associated with virtually no side-effects.

PMID- 15841786
TI  - Tunica albuginea acellular matrix graft for treatment of Peyronie's disease--an
      experimental study in dogs.
AB  - OBJECTIVE: To study the value of an acellular matrix graft of the tunica
      albuginea for reconstruction of the penis in cases of severe Peyronie's disease.
      MATERIAL AND METHODS: In nine mongrel dogs, an acellular matrix graft of the
      tunica albuginea was used to cover a 30 x 10 mm2 tunical defect. Equal numbers of
      animals were sacrificed at 1, 3 and 6 months after surgery. Before death, an
      erection was induced by means of papaverine injection and cavernosography was
      performed. After death the penis was prepared for histopathological study.
      RESULTS: All animals survived the surgery and none developed haematoma, wound
      infections or dehiscence. All dogs developed a straight, rigid erection.
      Cavernosography showed patent corpora cavernosa in all animals. The papaverine
      injection and cavernosographic results did not change over time. Inspection of
      the graft site and measurement of its length and width showed healing with no
      contracture. Histologically, the regenerated matrix appeared thicker than the
      neighbouring tunica albuginea in the 1-month group; otherwise the appearance was
      normal. Gradual orientation of the fibrocytes, capillaries and collagen fibres
      was demonstrated at 1 month and was complete at 3 and 6 months. Comparison
      between an implanted tunica at 6 months and a control tunica from a normal dog
      showed no significant histological difference. CONCLUSION: A homologous acellular
      matrix graft of the tunica albuginea may be an alternative treatment for severe
      cases of Peyronie's disease.

PMID- 15841787
TI  - Apolipoprotein E polymorphism in 385 patients on renal replacement therapy in
      Sweden.
AB  - OBJECTIVE: To examine apolipoprotein (apo) E polymorphism and its possible link
      to kidney disease in all patients receiving renal replacement therapy in our
      region. MATERIAL AND METHODS: The apo E genotype, plasma (P) lipids, blood
      pressure and albumin excretion rate were determined retrospectively in 385
      patients. RESULTS: No differences in apo E genotype or the allelic frequencies of
      epsilon2, epsilon3 or epsilon4 were found between the patient group and a control
      group of 343 healthy individuals. The apo E3/E4 genotype, however, was found in
      only 1/24 patients with non-insulin-dependent diabetes mellitus (NIDDM), a
      significantly lower frequency than that seen in the rest of the patient group (p
      = 0.041). Similarly, the apo E4/E4 genotype was absent in patients with
      glomerulonephritis (GN) (p = 0.027). The relative frequency of the epsilon4
      allele in patients with GN (0.116) was significantly lower than that in the rest
      of the patients (0.193; p < 0.05) and that in the control group (0.186; p =
      0.027). Furthermore, 19/47 patients (40.4%) with autosomal dominant polycystic
      kidney disease (ADPKD) had the E3/E4 genotype, as compared to 77/338 (22.8%) in
      the rest of the patient group (p = 0.035; odds ratio 2.07; CI 1.09-3.92). An
      increase in the relative frequency of the epsilon4 allele was seen in the same
      diagnostic group: 0.29 vs 0.16 in the rest of the patient group (p = 0.0023). The
      mean P-cholesterol level in patients with the epsilon4 allele was 5.9 +/- 1.0
      mmol/l, compared to 5.0 +/- 1.1 mmol/l in patients without the epsilon4 allele (p
      = 0.026). CONCLUSIONS: In this study, variations in the frequencies of the apo
      epsilon4 allele and the apo E3/E4 and E4/E4 genotypes were found in patients with
      NIDDM, GN and ADPKD. This result may be a consequence of the effects of the apo
      epsilon4 and epsilon2 alleles on P-cholesterol and remnant lipoprotein levels.
      The decreased frequency of apo E3/E4 found in patients with NIDDM may be
      explained by the fact that the epsilon4 allele gives renoprotection against
      diabetic nephropathy by lowering plasma remnant lipoprotein levels. Conversely,
      there may be an association between the apo E3/E4 genotype and the epsilon4
      allele in patients with ADPKD, due to the effect of the epsilon4 allele in
      elevating P-cholesterol levels. The most plausible explanation for the absence of
      the apo E4/E4 genotype and the lower prevalence of the epsilon4 allele in
      patients with GN, which is known to result in a higher P-cholesterol compared to
      the epsilon2 and epsilon3 alleles, ought to be an increase in cardiovascular
      morbidity, which is known to be associated with a higher P-cholesterol level.

PMID- 15841788
TI  - Vasculogenic erectile dysfunction in renal transplant recipients--assessment of
      potential risk factors.
AB  - OBJECTIVES: This study was performed to determine the effects of renal
      transplantation on penile haemodynamics using pharmaco-stimulation and colour
      Duplex ultrasonographic examination and then to determine the possible vascular
      risk factors for impotence in these patients. MATERIAL AND METHODS: A total of
      100 renal transplant recipients (RTRs; 80 impotent, 20 potent) and 20 potent
      uraemic patients on haemodialysis waiting for transplantation (control group)
      were included in the study. The patients were evaluated by means of detailed
      medical and sexual histories, clinical examination and laboratory investigations.
      The severity of erectile dysfunction was assessed using the International Index
      of Erectile Function questionnaire. Pharmacodynamic penile Duplex ultrasonography
      was carried out for all patients. RESULTS: The following factors were more
      commonly associated with impotent compared to potent RTRs: older age, diabetes
      mellitus, a longer pre-transplant duration of uraemia, impaired graft function
      and the use of cyclosporin A-based immunosuppressive therapy. Arterial occlusive
      disease was identified among 11 RTRs (11%), all of whom were impotent. Impotent
      RTRs had a significantly lower penile blood flow compared to potent RTRs or
      controls. Age, duration of pre-transplant uraemia and cyclosporin A level had a
      negative impact on penile haemodynamic parameters. CONCLUSIONS: Penile vascular
      insufficiency is less common in RTRs than previously reported. The pathogenesis
      of penile arterial occlusive disease in impotent RTRs is mainly due to associated
      vascular risk factors. After unilateral interruption of the internal iliac
      artery, an adequate penile blood supply is maintained in the majority of cases.
      Early transplantation may delay or prevent the development of penile
      vasculopathy.

PMID- 15841789
TI  - Study of the quality of information given to patients participating in a clinical
      trial regarding chronic hemodialysis.
AB  - OBJECTIVE: To study the quality of the information provided to and the procedure
      for obtaining the consent of chronically ill patients participating in a clinical
      trial. All patients included in a clinical trial concerning a lipid-lowering
      treatment over a 1-year period were asked to participate in the present research
      ethical study. MATERIAL AND METHODS: Patients (n = 55) on hemodialysis or in a
      prerenal state were selected. About 2 weeks after being recruited, the patients
      received a questionnaire concerning different aspects of the information
      provided. None of those responsible for providing information and obtaining
      consent were aware of the research ethical study in advance. RESULTS: A total of
      44 patients answered the questionnaire (response rate 80%). All but one
      participant perceived the information provided as being very good or fairly good.
      None felt that they had been forced to participate in the trial. A total of 12
      patients stated that they had delegated the decision making to their doctor.
      Compared to the younger patients, elderly participants more often stated that
      they had only been informed orally (p = 0.027). Those who stated that they were
      only informed orally tended to let the doctor decide whether or not they should
      participate in the trial. CONCLUSIONS: The study indicates that, compared to
      younger patients, elderly patients tended to be informed about the trial only
      orally and were also inclined to let the doctor decide whether or not they should
      participate. Providing information both orally andin writing and providing
      sufficient time for consideration may improve the informed consent process for
      severely ill patients.

PMID- 15841790
TI  - Temporary urethral stenting for membranous urethral stricture helps complete
      healing without compromising continence.
AB  - We report the case of a patient with a recurrent membranous urethral stricture
      who was treated with temporary implantation of a UroLume endoprosthesis and
      recovered completely, without any sphincteric insufficiency or stricture
      recurrence, during a 1-year follow-up period.

PMID- 15841791
TI  - Upper urinary tract complications in pregnant women with an ileal conduit.
      Lessons learned from two cases.
AB  - We describe the occurrence of severe upper urinary tract complications during
      pregnancy in two women with an ileal conduit. The first patient developed several
      episodes of left pyelonephritis throughout the duration of her pregnancy but
      never received proper antibiotic prophylaxis. Intravenous urography performed
      after delivery documented bilateral staghorn kidney stones and a non-functioning
      left kidney. The second patient developed severe left loin pain and a high
      temperature during the fourth month of pregnancy after discontinuing antibiotic
      prophylaxis. An MRI urogram demonstrated compression of the ureter by the foetus.
      Symptoms were relieved as soon as the antibiotic prophylaxis was resumed and the
      pain remained under control with the occasional use of paracetamol until
      delivery. Based on these observations it appears that the left upper urinary
      tract may be more prone to dilatation in pregnant patients with an ileal conduit
      and antibiotic prophylaxis is mandatory throughout the duration of the pregnancy
      in order to minimize the risk of severe upper urinary tract complications.

PMID- 15841792
TI  - Distribution of thyrostimulin in the rat: an immunohistochemical study.
AB  - OBJECTIVE: To identify the distribution of thyrostimulin, a heterodimer of
      glycoprotein hormone subunits (A2 and B5) by immunohistochemistry in the rat
      tissues using specific antipeptide anti-serum which we recently produced. METHOD:
      Anti-thyrostimulin antibody was raised in New Zealand white rabbits immunized
      with a conjugate of synthetic A2 or B5 with bovine serum albumin.
      Immunohistochemical analysis was performed by avidin-biotin complex method.
      RESULTS: Thyrostimulin immunoreactivity was visualized in the anterior pituitary,
      central nervous system, adrenal gland, stomach, duodenum, pancreas and testis.
      When using antiserum pre-incubated with synthetic peptides or rat pituitary
      homogenate which contains thyrostimulin peptide, no significant stain of the
      pituitary was detected. CONCLUSION: These findings suggest that thyrostimulin is
      widely distributed and that the method used is valuable in studying the
      distribution of thyrostimulin in rats.

PMID- 15841793
TI  - Gonadal and adrenal steroid hormones in plasma and synovial fluid of patients
      with rheumatoid arthritis.
AB  - OBJECTIVES: Gonadal and adrenal steroids were shown to affect multiple immune
      processes including inflammatory response. These effects were documented,
      specifically, through an influence on local productions of cytokines and the
      functions of synovial cells at the site of inflammatory processes. The aim of
      this study was to investigate the levels of selected hormones in synovial fluid
      of knee joints of patients with rheumatoid arthritis (RA) and with osteoarthrosis
      (OS, control group). METHODS: The concentrations of cortisol (CORT), 17-beta
      estradiol (ES), dehydroepiandrosterone (DHEA), testosterone (TE), progesterone
      (PRG), and aldosterone (ALD) were determined in plasma and synovial fluid.
      RESULTS: Significant positive correlations between the levels in plasma and
      synovial fluids were observed in hormones ES, PRG, TE, DHEA and ALD. In most
      hormones, the levels in synovial fluids were similar as in plasma; however, the
      content of ALD was higher in synovial fluid as compared to plasma. Higher levels
      of ES (in females), DHEA (in males), and ALD were observed in plasma and synovial
      fluids of RA patients as compared to OS patients. After adjustment to age, no
      significant RA vs. OS difference was noted in ES, TE, DHEA, PRG, and CORT in
      plasma and synovial fluid. Age-adjusted ALD concentration tended to be higher in
      synovial fluid of RA patients as compared to OS patients. The ratio of ES/TE
      concentrations in synovial fluid was significantly higher in male RA patients
      compared to OS group. Also the ES/CS and ES/DHEA ratios in synovial fluid were
      elevated in RA patients in comparison to controls. CONCLUSIONS: These results
      demonstrated the prevalence of pro-inflammatory hormones in synovial fluid of RA
      patients, suggesting the possible role of these steroid hormones in inflammatory
      processes.

PMID- 15841794
TI  - Neuroendocrine or behavioral effects of acute or chronic emotional stress in
      Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats.
AB  - OBJECTIVE: Spontaneously hypertensive rats (SHR) selected from Wistar Kyoto (WKY)
      strain represent an animal model of human essential hypertension. This strain of
      rats is known by excessive neuroendocrine and cardiovascular responses under
      stress. The aim of the present study was: 1. To compare the reactivity of
      hypothalamic-pituitary-adrenocortical axis (HPA) to acute mild stress of handling
      between SHR and WKY rats, 2. to compare the behavioral activity of both strains
      under basal conditions and during chronic unpredictable emotional stress.
      METHODS: Seven to eight weeks old male SHR and WKY rats bred in the Physiological
      Institute, Academy of Sciences of the Czech Republic (Prague) were used. Acute
      stress was induced by 2-minute handling of the animals in their cage. Blood
      plasma was analyzed for ACTH and corticosterone (CORT) by specific
      radioimmunoassay. Chronic unpredictable stress lasted 20 days and consisted of
      random exposures to following interventions: Light on or off for 24 h,
      overcrowding i.e. pooling the rats from two cages into one (size 24 x 39 x 23 cm)
      for 24 h, isolation by placing a single rat into one cage for 24 h, new hierarchy
      by mixing 4 rats from two different cages for 24 h, limited access to food or
      water for 1 hour in one day between 3 and 6 p.m., inescapable foot shock (20
      shocks, duration 5 s, intensity 10 mA, intershock interval 30 s), tilting the
      cages for 24 h. The sequence of individual stress exposures was the same in all
      rats. On day 6, 10 and 20, behavioral activity was measured using the elevated
      plus-maze in non-stressed control and stressed rats. The results were evaluated
      by non parametrical Kruskal-Wallis test followed by Mann-Whitney U-test. RESULTS:
      The two-minute handling resulted in a significantly higher activation of HPA in
      the SHR than in the WKY rats (plasma ACTH: 350 +/- 65 pg/ml for SHR vs. 97 +/- 17
      pg/ml for WKY p<0.01; plasma corticosterone: 2.8 +/- 1.4 mg/100 ml for SHR vs.
      0.7 +/- 0.06 mg/100 ml for WKY p<0.05). In WKY rats no activation of HPA was
      observed. Elevated plus-maze anxiety test showed inverse behavioral pattern
      between SHR and WKY rats. In the first test of anxiety the number of open arm
      entries (OAE) as well as total mobility expressed as total arm entries of the SHR
      was lower than of the WKY rats (p<0.01) without any difference between stressed
      and non-stressed animals in either strain. It was gradually increasing in
      stressed and non-stressed SHR in subsequent sessions markedly exceeding the
      activity of WKY rats (p<0.01). Stressed WKY rats showed less OAE and total
      mobility than their controls (p<0.01). CONCLUSIONS: Our results show enhanced
      neuroendocrine response to acute handling and enhanced anxiety in acute novelty
      stress in SHR comparing to WKY rats which suggests a common mechanisms for
      neuroendocrine and behavioral changes. These results further underline the lack
      of anxiety related behavior of SHR under chronic emotional stress.

PMID- 15841795
TI  - Radioimmunoassay for aquaporin-9.
AB  - OBJECTIVE: To develop radioimmunoassay for aquaporin-9 (AQP9) and search for its
      presence in certain rat tissues. METHODS: Anti-AQP9 antiserum has been raised in
      New Zealand white rabbits immunized with a conjugate of synthetic AQP9 with
      bovine serum albumin. Radioiodination of AQP9 was performed by chloramin T method
      followed by purification of radioiodinated material on Sephadex G-25 column.
      RESULTS: The obtained antibody did not crossreact with other aquaporins,
      hypothalamic hormones, pituitary hormones, neuropeptides or gut hormones. The
      assay was performed with a double antibody system. AQP9 was extracted from the
      tissues with acid acetone. The dilution curve of acid acetone extracts of rat
      liver in the radioimmunoassay system was parallel to the standard curve. The
      recovery of tissue AQP9 was about 90%, and the intra-assay and inter-assay
      variations were 4.8% and 7.9%, respectively. AQP9 was found in the liver, testis
      and brain. CONCLUSION: These data suggest that this assay system is suitable for
      the estimation of AQP9 in the tissues.

PMID- 15841796
TI  - Effect of leptin on proliferative activity and vascular endothelial growth factor
      (VEGF) secretion from cultured endothelial cells HECa10 in vitro.
AB  - OBJECTIVE: The aim of this study was to check if leptin influences the
      proliferative activity and vascular endothelial grofth factor (VEGF) release from
      cultured mouse endothelial cells in vitro. METHODS: The murine cell line HECa10
      obtained from endothelial cells of mouse peripheral lymph nodes immortalised by
      transfection of plasmid with the gene for the large T antigen of Simian virus 40
      was used in the experiments. The proliferative activity of HECa10 cells was
      studied by Mosmann and VEGF release by ELISA methods. RESULTS: Murine leptin in
      concentrations from 5 to 25 ng/ml stimulated the proliferative activity of 72 h
      endothelial cell cultures and in concentrations from 0.5 to 25 ng/ml augmented
      the release of VEGF into supernatants of 24 h and 72 h cultured cells.
      CONCLUSION: Leptin stimulated proliferation and VEGF secretion of endothelial
      cells in vitro.

PMID- 15841797
TI  - Comparison of insulin sensitivity indices calculated from standard 3-sampled and
      frequently sampled oral glucose tolerance test.
AB  - OBJECTIVE: Three-sampled oral glucose tolerance test is the most frequently used
      method for evaluation of impairment of glucose homeostasis in daily clinical
      practice. The aim of this study was to answer the question if insulin sensitivity
      indices (ISI) calculated from standard 3-sampled oral glucose tolerance test
      (3SoGTT) provide adequate information compared to the outcome when calculated
      from frequently sampled oral glucose tolerance test (FSoGTT). METHODS: A total of
      73 subjects (aged 17-59 years, BMI 17.9-41.8 kg/m2) underwent a standard
      frequently sampled oral glucose tolerance test (FSoGTT). Selected indices of
      insulin sensitivity were calculated using plasma glucose and insulin
      concentrations from FSoGTT and from samples obtained in 0, 60 and 120 min of the
      oGTT (3SoGTT). Areas under the peripheral concentration curves of insulin and
      glucose (AUCi, AUCg) from both approaches were compared. RESULTS: Insulin
      sensitivity calculated from 3SoGTT was significantly higher compared to the
      sensitivity calculated from FSoGTT expressed as insulin sensitivity indices ISI
      Cederholm (ISI(Ced)) and ISI Matsuda (ISI(Mat)), p<0.001 and p<0.05,
      respectively. There was a difference in AUCg between values estimated from 3SoGTT
      and FSoGTT (p<0.05). These differences nearly disappeared when the BMI groups
      (normal weight and overweight/obese) were evaluated separately. No differences
      were found in AUCi and the AUCg:AUCi ratio between two approaches. CONCLUSIONS:
      It might be supposed that on using 3SoGTT the ISI(Mat) provides greater
      objectivity in assessing insulin sensitivity than ISI(Ced). Although insulin
      sensitivity is overestimated when calculated from 3SoGTT, the approach is still
      valuable for identifying subjects with insulin resistance.

PMID- 15841798
TI  - Static footprint analysis: a time-saving functional evaluation of nerve repair in
      rats.
AB  - Walking track analysis is a widely accepted technique for functional evaluation
      after sciatic nerve repair in rats, but it is labour-intensive. In 2000, Bervar
      described a time-saving digitised static footprint analysis. In that study there
      were good correlations between the traditional sciatic function index (SFI) and
      the newly-developed static sciatic index (SSI) and static toe spread factor
      (TSF), respectively. Despite promising results, static footprint analysis is
      still not widely used. The present study was designed to validate it. After
      transection of the sciatic nerve, end-to-end repair was assessed using video
      recorded dynamic and static footprints in 45 Wistar rats. We found an even better
      correlation between the SFI and both the SSI and the static TSF. In conclusion,
      static footprint analysis is a time-saving and easy technique for accurate
      functional assessment of peripheral nerve regeneration in rats.

PMID- 15841799
TI  - Effect of active site-inactivated factor VIIa on ischaemia/reperfusion injury in
      a porcine flap model.
AB  - In free flap surgery, restored blood flow following a lengthy ischaemic period
      may lead to necrosis as a result of ischaemia/reperfusion (IR) injury. This
      injury comprises both proinflammatory and prothrombotic events, where the tissue
      factor/factor VIIa complex probably has a key role. Active site-inactivated
      factor VIIa (FFR-rFVIIa) exerts an antithrombotic effect by binding to tissue
      factor without initiating coagulation. In this study we have evaluated the
      potential protective effects of FFR-rFVIIa in IR injury. Bilateral
      musculocutaneous latissimus dorsi flaps in 16 pigs were made ischaemic for eight
      hours, then given 1 mg/kg/flap of FFR-rFVIIa or vehicle intra-arterially, and
      reperfused for 10 hours. The viable:necrotic tissue ratio, and accumulation of
      radiolabelled leucocytes, fibrinogen, and platelets were measured. There was no
      effect on tissue survival, but radiolabelled components in viable tissue were
      increased, though not significantly so. We conclude that FFR-rFVIIa did not
      prevent IR injury, indicating that tissue factor-mediated coagulation is not an
      important determinant of IR injury in this setting.

PMID- 15841800
TI  - Quality of life after reduction mammaplasty.
AB  - Reduction mammaplasty is a common procedure in plastic surgery. Patients seek the
      operation for neck and lower back pain, and social and emotional problems. The
      evaluation of health results based on the patient's opinion has become an
      important and reliable method for the analysis of alterations resulting from
      treatment. To evaluate the impact of plastic surgery on the quality of life of
      patients with mammary hypertrophy we used the SF-36 standardised questionnaire in
      a prospective study of 44 patients preoperatively and three and six months
      postoperatively. There were significant improvements in seven of the eight
      aspects of the SF-36 (physical function, physical role, pain, energy, social
      function, emotional role, and mental health). Only general health was unchanged.

PMID- 15841801
TI  - Advanced Kienbock's disease treated with implantation of a tendon roll and
      temporary partial fixation of the wrist.
AB  - Twenty-one patients with advanced Kienbock's disease were treated by implantation
      of a tendon roll and temporary partial fixation of the wrist. There were 13 women
      and eight men. Their ages at the time of operation ranged from 24 to 72 years.
      According to Alexander and Lichtman's classification, 12 patients were stage IIIb
      and nine stage IV. After implantation of the tendon roll, the scaphotrapezio
      trapezoidal joint was fixed with Kirschner wires in 19 patients, and the
      scaphocapitate joint with absorbable pins in two. Postoperative wrist pain
      disappeared in nine patients and was reduced in 12. The mean postoperative total
      arc of flexion and extension of the wrist increased from 91 degrees to 103
      degrees, and mean grip strength improved from 11.5 to 17.2 kg. Loosening of
      Kirschner wires during partial fixation of the wrist was seen in six cases, and
      required early removal of the loose wires.

PMID- 15841802
TI  - Epidemiology of hand injuries in a middle-sized city in southern Sweden: a
      retrospective comparison of 1989 and 1997.
AB  - Case notes of patients with hand injuries that required referral to our
      department in 1989 and 1997, were analysed retrospectively. The incidence of such
      an injury was at least 7/1000 inhabitants/year (12% of the patients seen in the
      orthopaedic Accident and Emergency department). Most of the patients were young
      men with minor injuries, most commonly injured during leisure activities. Only
      22% of the patients who worked were injured at work, but such injuries increased
      the risk of admission to hospital. The amount of sick leave was significantly
      shorter in 1997, and 77% of the workers were off work for less than two months.
      There was a reduced risk of injury during July, November, and December, and on
      Tuesdays. Type and range (type/mechanism/severity) of injuries differed slightly
      between the years and among the various age groups. Epidemiological data about
      hand injuries that affect young patients of productive age, are important to
      optimise resources and organisation of the health care system.

PMID- 15841803
TI  - Non-invasive measurement of tendon excursion with a colour Doppler imaging
      system: a reliability study in healthy subjects.
AB  - The excursion of the flexor digitorum profundus tendon during active flexion of
      the third finger was measured with colour Doppler imaging in 10 healthy
      volunteers. Repeated measurements were made by one observer in three sessions to
      assess the test-retest reliability. An analysis of variance (ANOVA) was done to
      find out the multiple sources of measurement error. The intraclass correlation
      coefficient was 0.81. For single measurements, the standard error of measurement
      was not more than 0.17 cm. The smallest detectable difference between two
      consecutive measurements was 0.48 cm. The test-retest reliability of colour
      Doppler measurements of excursion of the flexor digitorum profundus III tendon
      (FDP III) in healthy subjects is good. With series of 25 flexion movements,
      colour Doppler imaging is applicable in the assessment of tendon excursions in
      patients.

PMID- 15841804
TI  - Midline cleft of the lower lip associated with Robinow syndrome.
AB  - Robinow syndrome (also named "fetal face syndrome") includes a series of
      anomalies including mesomelic brachymelia, bifid terminal phalanges of the hands
      and feet, abnormalities of vertebrae and ribs, and hypoplastic external
      genitalia. A midline cleft of the lower lip and mandible is an extremely rare
      maxillofacial deformity. Seventy cases have so far been described to our
      knowledge. We report a patient with Robinow syndrome and midline cleft of the
      lower lip and mandible and describe the reconstruction of these anomalies. We
      propose that this anomaly should be added to the range of malformations
      associated with the syndrome.

PMID- 15841805
TI  - Bronchogenic cyst of the shoulder.
AB  - An 8-month-old girl presented with a painless mass on her left shoulder that was
      noticed by her mother. Ultrasonography and magnetic resonance imaging (MRI)
      showed a well-defined subcutaneous cystic mass. The excised cyst was lined with
      ciliated pseudostratified columnar epithelium with occasional goblet cells and
      diagnosed as a bronchogenic cyst. She made a good recovery.

PMID- 15841806
TI  - Transfer of a free flap from an acutely burned donor site.
AB  - A deep burn injury of the right upper extremity in a 12-month-old boy was
      successfully reconstructed with a tensor fascia lata free flap taken from an
      acutely burned donor thigh, as a healthy donor site was not available elsewhere.
      The result was satisfactory.

PMID- 15841807
TI  - Anterior interosseous nerve palsy after reduction and percutaneous pinning of
      open fractures of the radius and ulna.
AB  - We report a case of an anterior interosseous nerve palsy after closed reduction
      and percutaneous pinning of open fractures of the radius and ulna in an adult.
      Operative findings showed that the anterior interosseous nerve was trapped
      between the distal and proximal part of the fractured radius. Treatment by
      neurorrhaphy gave a satisfactory result.

PMID- 15841808
TI  - Posterior interosseous nerve injury complicating ulnar osteotomy for a missed
      Monteggia fracture.
AB  - We describe a 6-year-old boy with a posterior interosseous nerve injury after an
      ulnar osteotomy for a chronic Monteggia lesion. Although the first consultant did
      an ulnar osteotomy to reduce the radial head, the posterior interosseous nerve
      palsy did not recover. Next we found that the posterior interosseous nerve had
      been drawn into the radiocapitellar joint. It is important to confirm
      interposition of the nerve at the radiocapitellar joint during corrective
      osteotomy for a chronic Monteggia lesion.

PMID- 15841809
TI  - Carpal tunnel syndrome caused by an intraosseous ganglion of the capitate.
AB  - Intraosseous ganglions often arise in the foot and ankle but are less common
      within the carpal bones. We present a case of an intraosseous ganglion of the
      capitate bone associated with compression of the median nerve that was seen on
      plain radiographs and magnetic resonance images.

PMID- 15841810
TI  - Salivary mutans streptococci and dental caries in three-year-old children after
      maternal exposure to chewing gums containing combinations of xylitol, sorbitol,
      chlorhexidine, and fluoride.
AB  - The aim of this study was to evaluate the effect of maternal use of chewing gums
      containing combinations of xylitol, sorbitol, chlorhexidine, and fluoride on
      salivary mutans streptococci (MS) counts and caries prevalence in the mothers' 3
      year-old children. After screening 416 women with newborn babies, 173 mothers
      with high counts of salivary MS were randomly assigned into 3 experimental
      chewing gum groups containing (A) xylitol (n = 61), (B)
      chlorhexidine/xylitol/sorbitol (n = 55), and (C) sodium fluoride/xylitol/
      sorbitol (n = 57). Mothers with low or medium MS counts formed a reference group
      (D) without any intervention (n = 232). The participants in the experimental
      groups were instructed to chew one piece of the gum for 5 min 3 times a day. The
      chewing regimen started when the child was 6 months old and was terminated 1 year
      later. The outcome measures were salivary MS counts and caries prevalence at the
      age of 3 years. Bacterial enumeration was carried out with a chair-side technique
      and caries (defs) was scored by clinical examination. Medium and high counts of
      salivary MS were found in 13%, 16%, and 22% in groups A, B, and C, respectively.
      The mean defs was 0.1 in group A, 0.2 in group B, and 0.4 in group C. The
      differences concerning salivary MS and caries were not statistically significant.
      The MS counts and caries prevalence in children of mothers with low MS counts
      (group D) were similar to those found in groups A and B. In conclusion, lower but
      non-significant levels of salivary MS and dental decay were observed in 3-year
      old children to mothers who used high-content xylitol gums compared with those
      who used lower amounts of xylitol. The efficiency of this type of targeted
      intervention in a low-caries community may be questioned.

PMID- 15841811
TI  - Prevention of caries in children by preventive and operative dental care for
      mothers in rural Anatolia, Turkey.
AB  - The aim of this study was to prevent or delay the transmission of cariogenic
      bacteria, and hence the early development of caries in children, by preventive
      methods targeted at the mother. This field study was carried out in rural
      southeastern Anatolia, Turkey, where access to dental care is limited. Twenty
      seven mother-infant pairs were followed for 2 years. The infants were between 2
      and 18 months old when the study began. Mothers in the control group (n = 12)
      received a simple care and advice program, and those in the test group (n = 15)
      followed a preventive and operative regimen. The occurrence and the incremental
      occurrence of caries in the mothers and children in both groups were determined
      annually. Using a commercial kit, levels of mutans streptococci and lactobacilli
      in saliva and plaque were measured in the children at 6-month intervals. The
      microbial data demonstrated that the children of mothers in the test group had
      significant reductions in mutans streptococci and lactobacilli in plaque (P<
      0.001), whereas no such trend was observed in control children during the 24
      month monitoring period (P> 0.05). After 12 months, the occurrence of caries
      (dfs) was significantly lower in the test group than in the control group (0.13+/
      0.35 vs 1.67+/-1.30, respectively; P< 0.001). A similar difference was observed
      after 24 months (0.2+/-0.56 vs 3.17+/-1.70, respectively; P< 0.001). The results
      of this 2-year study demonstrate that a preventive and operative regimen designed
      to reduce oral bacterial levels in mothers can be remarkably effective in
      reducing the incidence of caries in infants in rural southeastern Anatolia. Owing
      to the prevalence of a traditional lifestyle based on close-knit families and
      clans, this region is an advantageous environment for the reduction of bacterial
      transmission from mother to child, while largely excluding other sources of
      infection for the child.

PMID- 15841812
TI  - Patients' choice of dental treatment following examination at a specialty unit
      for adverse reactions to dental materials.
AB  - The Dental Biomaterials Adverse Reaction Unit in Bergen, Norway, is a national
      unit for the examination of patients with suspected adverse reactions to dental
      materials. The aim of this study was to investigate whether patients with
      suspected adverse reactions to dental materials experienced improvement in health
      after dental restorations had been replaced, and whether they had acted according
      to the recommendations of the Unit. A questionnaire was sent to 358 patients who
      had been examined at the Unit 18 months to 7 years earlier. Of the 207 patients
      who completed the questionnaire, 85 had had restorative materials replaced with
      other types of materials. A majority had had amalgam fillings replaced. After
      replacement, 51 patients reported an improvement in health. Twelve patients
      reported that they felt worse after replacement. The Unit recommended replacement
      of materials in 31 patients, of whom 24 followed the recommendation. Among 176
      patients who were not given specific recommendations as to replacement of dental
      materials, 67 had had their restorations replaced, and 40 had started to have
      them replaced. It appears that the examination at the Dental Biomaterials Adverse
      Reaction Unit is one of several inputs that influence a person's decision to
      replace dental materials.

PMID- 15841813
TI  - Resting and stimulated whole salivary flow rates in Sjogren's syndrome patients
      over time: a diagnostic aid for subsidized dental care?
AB  - The aim of the present study was to evaluate Swedish and Norwegian criteria
      currently applied in the assessment of eligibility for subsidized dental care of
      Sjogren's syndrome (SS) patients. These criteria are partly based on a single
      salivary test showing a resting whole salivary secretion rate of < or =0.1
      mL/min. Thirty secondary Sjogren (SSS) patients (29 F and 1 M) participated for
      the duration of the study, in which resting (RWS) and stimulated (SWS) whole
      salivary flow rates were collected in the morning and afternoon, over 3
      consecutive weeks, once per week, as well as at different times over a 5-year
      period. Twenty patients presented levels of RWS flow rates of < or =0.1 mL/min on
      one or more occasions over a 3-week period, while 8 of these also exceeded, on
      one or more occasions, the cut-off level of 0.1 mL/min, indicating that salivary
      flow rates varied over time. Six patients showed consistently low secretion rates
      of RWS as well as of SWS, estimated as < or =0.1 mL/min and <0.7 mL/min,
      respectively. Based on the results, salivary tests that are to be used as a
      diagnostic aid for SS diagnosis, and thus as a basis for inclusion within the
      subsidy net for dental care, must be taken on several occasions in order to more
      accurately give information about salivary gland function. In line with this,
      current regulations governing the eligibility of SS patients within subsidized
      dental care programs should be reviewed.

PMID- 15841814
TI  - Salivary buffer capacity in relation to menarche and progesterone levels in
      saliva from adolescent girls: a longitudinal study.
AB  - The aim of this study was to investigate the relationship between salivary buffer
      capacity and menarche, and to explore any association with levels of the sex
      hormone progesterone in stimulated whole saliva in adolescent girls. The material
      comprised 162 girls, 12 years of age at baseline in the 6th grade, who were
      followed for 3 years. Every 4th month, a stimulated whole saliva sample was
      collected, secretion rate and buffer capacity were determined, and information
      was gathered on menarche, ongoing menses, and caries increment. Once yearly, the
      salivary concentration of progesterone was determined with an enzyme immunoassay
      kit. The results showed a significantly impaired salivary buffer capacity over
      the years (P < 0.05). Low buffer capacity was significantly correlated with low
      secretion rate (r = 0.42; P< 0.001) and DMFT increment (r=0.20; P<0.05). Pre
      menarche buffer capacity did not differ from the postmenarche scores. The
      concentration of progesterone in saliva increased with age but displayed no
      significant relationship to buffer capacity, flow rate, or caries increment. In
      conclusion, the findings of this study suggest that the salivary buffer capacity
      may be impaired over the adolescent years in females, but the reason remains
      unclear.

PMID- 15841815
TI  - Correlation between TNFalpha in gingival crevicular fluid and body mass index in
      obese subjects.
AB  - The aim of this study was to investigate the relationship between body mass index
      (BMI kg/m2), the inflammatory mediator tumor necrosis factor alpha (TNFalpha),
      and interleukin-8 (-8) in gingival crevicular fluid (GCF) from 32 obese subjects
      aged between 13 and 24 years. Gingival inflammation (GBI %), pathological pocket
      depths, and alveolar bone loss diagnosed on radiographs were recorded. The GCF
      was collected from six sites per subject using periopaper, and the volume was
      determined using Peritron 8000. The levels of TNFalpha and IL-8 were determined
      using ELISA kits. Within the whole group, there was no significant relationship
      between BMI and the variables age, GBI %, number of periodontal pockets, smoking,
      and the levels of TNFalpha or IL-8. In subjects with BMI > or =40, however, there
      was a statistically significant correlation (r= 0.74, P< 0.01) between the level
      of TNFalpha in GCF and BMI. The correlation coefficient between BMI and TNFalpha
      in subjects with BMI > or =40 differed significantly (P< 0.05) compared to that
      between subjects with BMI <40. The level of TNFalpha in GCF was positively
      correlated (P< 0.05) with BMI in subjects with no periodontal pathological
      pocket. No significant correlation was found between the level of IL-8 and BMI.
      The results indicate that BMI positively correlates with TNFalpha in GCF in the
      group of young subjects with BMI > or =40 as well as in the subjects with no
      pathological periodontal pocket (> or =4 mm) and that TNFalpha in GCF may be
      affected by the obese condition through a systemic effect.

PMID- 15841816
TI  - Effects from pretreatment of stannous fluoride versus sodium fluoride on enamel
      exposed to 0.1 M or 0.01 M hydrochloric acid.
AB  - Preventing enamel erosions caused by acidic soft drinks or from vomiting during
      eating disorders is a challenge in current dental research. The aim of this study
      was to examine whether pretreatment of dental enamel with a solution of 0.4% SnF2
      could prevent dissolution of human enamel exposed to solutions of 0.1 M HCl, pH
      1.2 or 0.01 M HCl at pH 2.2. Human enamel was pretreated for 18 h with a solution
      of 0.4% SnF2 and with control solutions of 2% NaF or distilled water, and then
      exposed to HCl solutions. Similar experiments were performed with teeth treated
      for 2 min SnF2 and then 4 min HCl. The effect was monitored by scanning electron
      microscopy (SEM) and by chemical analysis. At pH 2.2, NaF and water treatments
      showed minor inhibition of enamel dissolution, whereas SnF2 inhibited
      demineralization significantly also after 2 min pretreatment and 4 min HCl
      exposure. At pH 1.2, SEM showed severe dissolution of the enamel surfaces
      regardless of pretreatment. As pH of stomach vomit is usually > 1.5, SnF2 may be
      an interesting agent for use in the treatment and prevention of dental erosions
      even in patients with frequent vomiting episodes.

PMID- 15841817
TI  - Effect of different frequencies of preventive maintenance treatment on dental
      caries: five-year observations in general dentistry patients.
AB  - A long-term study in adults at a public dental clinic in Sweden was initiated to
      evaluate the relative effectiveness of prophylactic treatments on the progression
      of dental caries and periodontal discase. With treatments scheduled every 3rd,
      6th, 12th or 18th month, this report presents results on caries for the 3-month,
      6-month and 18-month groups, and evaluates the impact of various caries-related
      risk factors. Caries increment over approximately 5 years was determined by
      adding clinical and radiographic findings of manifest primary and secondary
      caries during the study. Overall caries activity among all 105 participating
      individuals was low to moderate. No significant differences for caries on any of
      the various tooth surfaces or for total caries were observed among the three
      groups. Multiple regression analysis with 5-year caries increment as dependent
      variable showed that the following factors had a statistically significant
      association with caries increment: percentage filled surfaces at baseline
      examination, dietary score, plaque score, and number of mutans streptococci and
      lactobacilli in saliva. Non-significant factors included number of preventive
      treatments provided during the 5-year interval. The results of this long-term
      trial suggest that preventive treatments as often as every 3 6 months may not be
      justified in the case of patients with low to moderate caries activity.

PMID- 15841818
TI  - Evaluation of caries risk factors and effects of a fluoride-releasing adhesive
      material in children with insulin-dependent diabetes mellitus (IDDM): initial
      first-year results.
AB  - The aims of this study were to evaluate the prevalence and risk factors of dental
      caries, and to determine whether there is any relationship between a fluoride
      releasing adhesive material and the development of dental caries in the first
      year in children with insulin-dependent diabetics (IDDM). The average age of the
      subjects was 4-15 years, and they had been suffering from IDDM for at least 2
      years. The DMF/df(t) indices of 70 patients were calculated and total HbA1 (%)
      (glucose levels of blood) values were recorded from the medical records after
      clinical examination. The mean DMF/df(t) values of poorly controlled subjects
      (HbA1 values over 13%) were significantly higher than those of moderately (HbA1,
      10.0-12.9%) and well-controlled (HbA1 values, <10%) subjects. The levels of
      salivary mutans streptococci (MS) and lactobacilli (LB) and the pH of paraffin
      stimulated whole saliva were measured in diabetic patients. Salivary MS and LB
      scores of the poorly controlled subjects were significantly higher (2.5+/-0.7 and
      2.1+/-1.0) than those of the moderately (1.6+/-0.9 and 1.1+/-0.8) and well
      controlled (1.2+/-1.0 and 0.8+/-0.8) subjects. The mean pH values among all
      subjects were not statistically significant. All dental caries were restored with
      a fluoride-releasing adhesive material. At the end of the first year, no new
      caries or lost restorations were observed in these patients. Moreover, the rate
      of MS in the poorly and moderately controlled subjects was considerably reduced.
      However, no significant statistical reduction of MS was determined in the well
      controlled subjects. The level of lactobacilli in the poorly controlled,
      moderately controlled, and well-controlled subjects was reduced.

PMID- 15841819
TI  - Now we are ten...

PMID- 15841820
TI  - Manual laterality and task complexity in De Brazza's monkey (Cercopithecus
      neglectus).
AB  - We investigated manual specialisation of six Brazza monkeys, both under
      structured experimental conditions and while they engaged in unconstrained
      natural behaviour. Five tasks that varied in complexity, degree of visual
      guidance, and bimanual coordination were used in the experimental condition.
      Individual preferences were revealed for each task, and in the case of simple
      tasks the position of a monkey relative to the task device was shown to impact on
      manual preference. Strength of laterality and performance were not found to be
      related. Task complexity influenced strength, but not direction, of manual
      preference. The small number of animals precluded generalisation to population
      preferences but the large number of observations and choice of tasks can serve as
      model for the study of manual preferences in primates.

PMID- 15841821
TI  - Right hemispheric dysfunction in schizophrenia.
AB  - This study uses the Poffenberger (1912) paradigm, which compares the difference
      between "crossed" (stimuli and motor response areas are contralateral) and
      "uncrossed" (stimuli and motor response areas are ipsilateral) conditions to
      estimate interhemispheric transfer time. Simple reaction time (RT) was recorded
      to stimuli presented to the left visual field (LVF), right visual field (RVF), or
      bilaterally (BVF) in individuals with schizophrenia (n = 10) and controls (n =
      14), who responded using either the left or right hand. While the results provide
      no evidence for differences between the groups in information transfer between
      the hemispheres, the schizophrenia group were significantly slower to respond to
      LVF stimuli, suggesting right hemisphere dysfunction.

PMID- 15841822
TI  - Reliability of non-verbal laterality effects in the visual modality.
AB  - The present experiment investigated the reliability and magnitude of laterality
      effects in a non-verbal task in the visual modality. The use of a bilateral
      discrimination task in which participants indicated whether a centrally presented
      probe stimulus matched either of the bilaterally presented targets was presumed
      to provide control over attention deployment. This led to the prediction that a
      reliable left visual field advantage (LVFA) would be obtained. A total of 40
      right-handed undergraduate students completed the bilateral discrimination task
      twice in a test-retest design. Although relatively large test-retest correlations
      suggested that the laterality effect was quite reliable, a significant LVFA was
      obtained in the first testing session, and a right visual field advantage in the
      second one. This finding parallels results obtained in previous work with non
      verbal tasks and supports the notion that practice affects the direction of
      laterality effects. The discussion examines alternative explanations with
      emphasis on practice effects and possible attentional factors. A possible shift
      in the bivariate distribution of laterality scores is used as a tentative
      explanation of the apparent contradiction between the high test-retest
      reliability and the shift in laterality with practice.

PMID- 15841823
TI  - Asymmetric bias in perception of facial affect among Roman and Arabic script
      readers.
AB  - The asymmetric chimeric faces test is used frequently as an indicator of right
      hemisphere involvement in the perception of facial affect, as the test is
      considered free of linguistic elements. Much of the original research with the
      asymmetric chimeric faces test was conducted with subjects reading left-to-right
      Roman script, i.e., English. As readers of right-to-left scripts, such as Arabic,
      demonstrated a mixed or weak rightward bias in judgements of facial affect, the
      influence of habitual scanning direction was thought to intersect with
      laterality. We administered the asymmetric chimeric faces test to 1239 adults who
      represented a range of script experience, i.e., Roman script readers (English and
      French), Arabic readers, bidirectional readers of Roman and Arabic scripts, and
      illiterates. Our findings supported the hypothesis that the bias in facial affect
      judgement is rooted in laterality, but can be influenced by script direction.
      Specifically, right-handed readers of Roman script demonstrated the greatest mean
      leftward score, and mixed-handed Arabic script readers demonstrated the greatest
      mean rightward score. Biliterates showed a gradual shift in asymmetric
      perception, as their scores fell between those of Roman and Arabic script
      readers, basically distributed in the order expected by their handedness and most
      often used script. Illiterates, whose only directional influence was laterality,
      showed a slight leftward bias.

PMID- 15841824
TI  - Individual and setting differences in the hand preferences of chimpanzees (Pan
      troglodytes): a critical analysis and some alternative explanations.
AB  - Several recent papers have been critical at a theoretical and empirical level of
      the evidence of population-level right-handedness in chimpanzees and other great
      apes. For example, Palmer (2002) has recently argued that the evidence of
      population-level handedness in chimpanzees is weak because there are sampling
      biases in the data. McGrew and Marchant (1997) argue that all the evidence of
      right-handedness in apes is from captive animals and therefore the observed
      phenomenon has little ecological validity. In this paper, we address recent
      issues regarding the presentation and interpretation of other hand preference
      data and argue that chimpanzees are right-handed for some measures. We further
      argue that purported differences in hand use between wild and captive chimpanzees
      due to rearing environments are unfounded and we emphasise that more cooperative
      work between researchers working in captive and feral populations is needed to
      facilitate collection of data on common measures of hand preference.

PMID- 15841825
TI  - Does brain white matter growth expand the cortex like a balloon? Hypothesis and
      consequences.
AB  - Horrobin (2001) has proposed that phospholipid metabolism is linked to human
      brain growth, and that deviations in the metabolism may be linked to creativity
      as well as mental disorders. The present literature review leads to a framework
      or model which states that brain white matter growth causes the overlying cortex
      to expand tangentially, like a balloon, and that this expansion affects the
      cortex's capacity to differentiate afferent signals. The neuroanatomical
      description of this model is based on publications linking human white matter
      growth and mass to the thickness of the overlying cortex, and of some linking
      cortical thickness and surface area (inversely). The link between the surface
      area of a cortical region and its differentiation capacity is based on previous
      work on hemispheric differences and functional lateralisation in the human
      auditory cortices. The link between differentiation capacity and inappropriate
      responses or "loose associations" is based on publications linking perceptual
      deficits and abnormal cortical structure, especially abnormal laterality.
      Finally, perceptual deficits have been linked to aspects of schizophrenia or
      other "disorders".

PMID- 15841826
TI  - Understanding obstacles to the recognition of and response to dementia in
      different European countries: a modified focus group approach using
      multinational, multi-disciplinary expert groups.
AB  - Experts from eight European countries (Belgium, France, The Netherlands, Ireland,
      Italy, Portugal, Spain and the United Kingdom) and the disciplines of clinical
      psychology, general practice, geriatric medicine, old age psychiatry, medical
      sociology, nursing and voluntary body organisation met in 2003 to explore
      obstacles to recognition of and response to dementia in general practice within
      Europe. A modified focus group methodology was used in this exploratory process.
      Groups were conducted over a two-day period, with five sessions lasting 1-1.5
      hours each. An adapted nominal group method was used to record themes arising
      from the group discussion, and these themes were used in a grounded theory
      approach to generate explanations for delayed recognition of and response to
      dementia. The overarching theme that arose from the focus groups was movement,
      which had three different expressions. These were: population movement and its
      consequences for localities, services and professional experience; the journey of
      the person with dementia along the disease process; and the referral pathway to
      access services and support. Change is the core issue in dementia care, with
      multiple pathways of change that need to be understood at clinical and
      organisational levels. Practitioners and people with dementia are engaged in
      managing emotional, social and physical risks, making explicit risk management a
      potentially important component of dementia care. The boundary between generalist
      and specialist services is a particular problem, with great potential for
      dysfunctionality. Stigma and ageism are variably distributed phenomena both
      within and between countries.

PMID- 15841827
TI  - The role of hope in psychotherapy with older adults.
AB  - The positive impact of psychotherapy upon the mental health problems of older
      people is increasingly accepted. However little attention has been paid to the
      role of hope in working therapeutically with older adults. Three relevant bodies
      of literature, namely adult psychotherapy, hope in older adulthood, and coping
      with chronic and terminal illness, provide a starting point for examining the
      therapeutic uses of hope. However, it is argued that these literatures cannot
      provide a sufficiently comprehensive conceptualisation of hope in psychotherapy
      with elders. Firstly, it is considered that hope in therapy is directly affected
      by key experiences of ageing, namely: facing physical and/or cognitive
      deterioration and facing death. Also, these three bodies of literature have
      tended to dichotomise hope as either beneficial and adaptive or dysfunctional and
      maladaptive. A developmental perspective is used to critique this dichotomy and a
      clinical framework is provided which examines the role and utility of hope in
      older adult psychotherapy from a more integrated viewpoint embedded in the
      client's life history. The framework is comprised of three types of 'hope work':
      'facilitating realistic hope,' 'the work of despair' and 'surviving not
      thriving'. Suggestions are made about how this work may be carried out and with
      whom.

PMID- 15841828
TI  - Vocally disruptive behaviour in dementia: development of an evidence based
      practice guideline.
AB  - Vocally Disruptive Behaviour (VDB) is a term that includes screaming, abusive
      language, moaning, perseveration, and repetitive and inappropriate requests. It
      is one of the most challenging behaviours for nursing home staff, caregivers for
      people with dementia, and other nursing home residents. As with other behavioural
      disturbances, multiple causal factors have been identified in the literature and
      individual cases may have a number of interacting factors. There is a lack of
      consensus about how to treat VDB. Systematic treatment studies are few and there
      is a lack of empirical data supporting the effectiveness of specific
      interventions commonly used in clinical practice. This hinders clinicians and may
      result in the use of inappropriate treatments. Our aim was to systematically
      review the literature in order to develop a practice guideline for the assessment
      and management of VDB. The review will examine the typology, risk factors and
      management of VDB.

PMID- 15841829
TI  - Understanding the outcomes of a psycho-educational group intervention for
      caregivers of persons with dementia living at home: a process evaluation.
AB  - This qualitative process evaluation study aimed to identify the primary processes
      of a psycho-educational group for caregivers of persons with dementia, in order
      to better understand intervention outcomes. Semi-structured interviews were
      conducted with 30 participants recruited from the experimental group of a
      randomised controlled trial. At pre-test, participants reported their
      expectations of the group. At post-test, they described their group experience,
      the most/least helpful aspects of the intervention, their most useful learning
      and their responses during a recent episode of disturbing behaviour by their
      relative. Results showed that the group delivered both educational and support
      processes. Support processes complemented educational processes. Participants
      learned coping strategies, with reframing playing a more important role than
      problem-solving or seeking social support. Daughters benefited more than spouses
      from educational processes. This study of group processes contributes to our
      understanding of the reported reduction in frequency of disturbing behaviours and
      of the change in caregivers' behaviours.

PMID- 15841830
TI  - Thought suppression and treatment outcome in late-life depression.
AB  - This study examined severity of depression, age of onset, and thought suppression
      as predictors of treatment outcome. Measures were taken pre-treatment, post
      treatment, and at six-month follow-up in 34 depressed older adults receiving the
      treatment protocol described in Lynch, Morse, Mendelson & Robins (Dialectical
      behavior therapy for depressed older adults, American Journal of Geriatric
      Psychiatry, 11, 33-45, 2003). Severity and chronicity of depression and higher
      levels of thought suppression were associated with higher depressive symptoms six
      months after treatment. Findings are consistent with research suggesting that
      severity and chronicity of depression predict poor clinical outcome. In addition,
      these results provide preliminary evidence that the tendency to cope with
      unwanted thoughts by deliberate attempts to not experience such thoughts may be
      an important pre-treatment predictor of outcome among depressed older adults.
      Larger studies are needed to explore whether thought suppression mediates long
      term recovery from depression.

PMID- 15841831
TI  - Decision-making capacity of elderly patients assessed through the vignette
      method: imagination or reality?
AB  - This article evaluates whether providing hypothetical or realistic information
      influences the assessment of decision-making capacity in elderly patients with
      (and without) cognitive impairment. Decision-making capacity was assessed by
      means of a clinical vignette that presented a choice about whether to undergo an
      endoscopic procedure. The following standards of decision-making capacity were
      evaluated quantitatively and qualitatively: ability to evidence a choice, to
      understand, to reason, and to appreciate a situation. The vignette was presented
      to patients in either a hypothetical or real situation. In the hypothetical
      situation cognitively impaired patients performed significantly poorer than
      cognitively non-impaired patients on all abilities associated with decision
      making capacity (with the exception of evidencing a choice). The realistic
      situation showed the same pattern among cognitively impaired and non-impaired
      patients in their ability to understand and in the total vignette score. Both
      types of patients reasoned about and appreciated the realistic situation equally
      well. Qualitative analysis revealed that patients gave comparable answers in both
      hypothetical and realistic situations. The answers were not related to standards
      of decision-making capacity. Moreover, personal circumstances were taken as a
      reference point for making a decision, regardless of the situation. We did not
      find any major differences between the hypothetical and realistic situation. Our
      findings do raise questions about the validity of hypothetical vignettes,
      however, especially when used with cognitively impaired persons.

PMID- 15841832
TI  - Older adults' health and changes in late-life drinking patterns.
AB  - This study focused on the prospective associations between older adults' health
      related problems and their late-life alcohol consumption and drinking problems. A
      sample of 1,291 late-middle-aged community residents (55-65 years old at
      baseline) participated in a survey of health and alcohol consumption, and was
      followed one year, four years, and 10 years later. Health-related problems
      increased and alcohol consumption and drinking problems declined over the 10-year
      interval. Medical conditions, physical symptoms, medication use, and acute health
      events predicted a higher likelihood of abstinence and less frequent and lower
      alcohol consumption. However, overall health burden predicted more subsequent
      drinking problems, even after controlling for alcohol consumption and a history
      of heavy drinking and increased drinking in response to stressors. Among older
      adults, increased health problems predict reduced alcohol consumption but more
      drinking problems. Older adults with several health problems who consume more
      alcohol are at elevated risk for drinking problems and should be targeted for
      brief interventions to help them curtail their drinking.

PMID- 15841833
TI  - Differential effects of everyday stress on the episodic memory test performances
      of young, mid-life, and older adults.
AB  - This research explored the differential association of everyday stress with the
      episodic memory test performances of young, mid-life, and older adults.
      Participants included 98 community-dwelling adults ranging in age from 19-89
      years. Everyday stress was assessed via the Perceived Stress Scale and the Elder
      Life Stress Inventory. A brief battery of episodic memory tasks was administered
      which included tests of Logical Memory, Verbal Paired Associates, Digit Symbol
      Substitution, and Digit Symbol Incidental Learning. Results suggest that everyday
      hassles and irritations as well as the accumulation of challenging life events
      may exacerbate age-related decline on episodic memory tests that require greater
      executive resources and more integrated and elaborative processing. The
      functional relationship between affective status and risk for dementia is
      discussed, and consideration of individual differences in everyday stress is
      suggested so as to allow more sensitive interpretation of episodic memory tests
      commonly used to discern mild cognitive impairment.

PMID- 15841834
TI  - Staff responses to challenging behaviour shown by people with dementia: an
      application of an attributional-emotional model of helping behaviour.
AB  - There is some evidence to suggest that staff beliefs and emotional responses to
      challenging behaviour shown by clients are critical factors in guiding their
      responses to such behaviour. The purpose of this paper was to apply Weiner's
      cognitive-emotional model of helping behaviour to staff working with people with
      dementia who exhibit challenging behaviour. The paper also aimed to explore the
      impact of staff burnout and professional group upon participants' responses to
      real-life experiences of challenging behaviour. The participants were 25 nurses
      and 26 psychologists. Methods included questionnaire measures and coding of
      spoken attributions using the Leeds Attributional Coding System. Non-parametric
      tests measured between-group differences and correlations between the key
      variables. There were few differences between the two professional groups for the
      key variables. Optimism and sympathy were generally associated with willingness
      to help, and burnout was associated with less willingness to help, low optimism
      and negative emotional responses to clients' behaviour. No consistent or robust
      role was found for attributions. The results are discussed in relation to
      alternative factors, which may promote or reduce staff helping behaviour in the
      context of services for people with dementia.

PMID- 15841836
TI  - [Complete attention to Chagas' disease patient. A proposal for the caring].

PMID- 15841835
TI  - Physical activity alone and with others as predictors of sense of belonging and
      mental health in retirees.
AB  - A high sense of belonging to the community and physical activity are associated
      with improved mental health in older people. The present study tested a model
      incorporating physical activities performed alone and with others as predictors
      of sense of belonging, depression and suicide ideation. One hundred and ninety
      four retired adults (87 males, 107 females, mean age 68 years) completed the Yale
      Physical Activity Survey, the Sense of Belonging Instrument, the Suicide Subscale
      of the General Health Questionnaire and the Zung Depression Inventory. Within the
      context of the model, neither participating in physical activities alone, nor
      with at least one other person, predicted sense of belonging, depression or
      suicide ideation. Having the abilities and motivation to belong was a predictor
      of participating in physical activities with others and actual feelings of
      belonging and contributed to predicting mental health in retirees. It was
      concluded that simply performing activities with others was not associated with a
      sense of belonging or mental health. Rather, sense of belonging may need to be
      facilitated in order for mental health to be enhanced.

PMID- 15841837
TI  - [Assessment of the pulmonary vascular blood supply in patients with pulmonary
      atresia, ventricular septal defect and aortopulmonary collateral arteries].

PMID- 15841838
TI  - [Myocardial remodeling after experimental acute myocardial infarction in rats.
      Effect of renin-angiotensin-aldosterone blockade].

PMID- 15841839
TI  - [Effect of estradiol on cardiopulmonary and metabolic responses of postmenopausal
      normotensive women undergoing cardiopulmonary exercise testing].

PMID- 15841840
TI  - [Effects of the state and specificity of aerobic training on the %VO2(max) versus
      %HR(max) ratio during cycling].

PMID- 15841841
TI  - [Acute coronary syndromes in the absence of significant coronary artery disease].

PMID- 15841842
TI  - [Prevalence of excessive weight and hypertension in a low-income urban
      population].

PMID- 15841843
TI  - [Myocardial revascularization without extracorporeal circulation in patients over
      75 years of age. Analysis of immediate results].

PMID- 15841844
TI  - [Postischemia stunned myocardium does not alter cardiac response to an elevation
      in contractile frequency].

PMID- 15841845
TI  - [Anticoagulation, pregnancy and cardiopathy. A triad, three dominions and five
      moments].

PMID- 15841846
TI  - [Heart transplantation in a patient with endomyocardial fibrosis].

PMID- 15841847
TI  - [Acute myocardial infarction and documented sudden death].

PMID- 15841848
TI  - [Single coronary artery: angioplasty with stent implantation].

PMID- 15841849
TI  - [Abstracts of the III Brazilian Congress on Cardiac Insufficiency, Salvador,
      Brazil, 25-27 November 2004].

PMID- 15841850
TI  - Youth attitudes towards tobacco control: a preliminary assessment.
AB  - The attitudes of Ontario youth toward the sale and price of cigarettes, making
      smoking against the law, and tobacco company truthfulness were assessed in 2001
      and compared to adult attitudes in 2000 and youth attitudes in 2003. Youth were
      more supportive of restricting cigarette sales and raising prices than adults,
      and more likely to agree that the government should make smoking against the law,
      but they were less distrustful of tobacco companies. In 2003, youth were more
      supportive of sales restrictions and making smoking illegal, and more distrustful
      of tobacco companies, than in 2001. More comprehensive assessments and continued
      monitoring of youth attitudes are needed.

PMID- 15841851
TI  - Inequalities in health and health services delivery: a multilevel study of
      primary care and hypertension control.
AB  - Delivery of health services is an important determinant of health. Restricted
      availability and access may result in health inequalities. To determine the
      extent of geographic variation in the delivery of health services and its effect
      on the health of community residents in terms of under-diagnosis and under
      treatment of hypertension, we carried out a multilevel study of participants in
      the 1995 Nova Scotia Heart Health Survey (n = 3,094). We used individual level
      survey data and health status measurements linked to geographical level
      information to examine the importance of adequate delivery of health services to
      the diagnosis and treatment of hypertension in the universal health care setting
      of the province of Nova Scotia. The delivery of primary care services across Nova
      Scotia varied moderately with physician visit rates ranging from 3.3 to 5.5
      visits per resident per year. There were neither substantial nor statistically
      significant differences in the diagnosis and treatment of hypertension among
      residents of communities varying in the delivery of health services. We concluded
      that a geographic variation in the delivery of primary care services is a public
      health concern that is not consistent with the objectives of universal coverage
      of health services; however, it was not confirmed to result in health
      inequalities.

PMID- 15841852
TI  - The late effects study: design and subject representativeness of a Canadian,
      multi-centre study of late effects of childhood cancer.
AB  - The Late Effects Study of the Canadian Childhood Cancer Surveillance and Control
      Program was designed to assess psychosocial and physical health outcomes among
      survivors of childhood cancer compared to general population controls. The
      objectives of this paper are to describe the design and methodology of the multi
      centre, retrospective cohort study, present clinical characteristics of the
      survivor population, and evaluate the representativeness of study controls.
      Response rates were 63% for surivors (n = 2,152) and 49% for controls (n =
      2,432). Survivors with germ cell turmours and carcinomas were slightly under
      represented among participants as were those who received more intense or
      multiple series of therapy. Study controls were similar to Census individuals
      based on marital and work status but did have a slightly higher level of
      education and income. Otherwise, no large or systematic differences were found.
      Thus, these long-term survivors and population controls can be validly studied to
      evaluate whether and to what extent survivors experience an excess of
      psychosocial or physical health problems compared to similarly aged Canadians who
      have never had cancer.

PMID- 15841853
TI  - Methods for estimating the labour force insured by the Ontario Workplace Safety
      and Insurance Board: 1990-2000.
AB  - This paper presents a methodology for estimating the size and composition of the
      Ontario labour force eligible for coverage under the Ontario Workplace Safety &
      Insurance Act (WSIA). Using customized tabulations from Statistics Canada's
      Labour Force Survey (LFS), we made adjustments for self-employment, unemployment,
      part-time employment and employment in specific industrial sectors excluded from
      insurance coverage under the WSIA. Each adjustment to the LFS reduced the
      estimates of the insured labour force relative to the total Ontario labour force.
      These estimates were then developed for major occupational and industrial groups
      stratified by gender. Additional estimates created to test assumptions used in
      the methodology produced similar results. The methods described in this paper
      advance those previously used to estimate the insured labour force, providing
      researchers with a useful tool to describe trends in the rate of injury across
      differing occupational, industrial and gender groups in Ontario.

PMID- 15841854
TI  - An epidemiologically-based needs assessment for stroke services.
AB  - Stroke is amenable to the entire spectrum of health services, ranging from
      prevention of its risk factors, to the treatment of acute stroke and
      rehabilitation and palliation of stroke. The aim of this study was to determine
      the number of persons with the capacity to benefit from evidence-based effective
      stroke services. Population-based survey and registry data along with published,
      evidence-based recommendations for services were used to determine the number of
      persons in Eastern Ontario with stroke (including risk factors, acute stroke and
      chronic stroke) and their related need for services (including prevention
      programs, diagnostic services, treatment of acute stroke and rehabilitation).
      These estimates were then compared to the actual provision of these services.
      Estimates of the need for effective services exceeded the provision of all
      services with the exception of pharmacologic treatment for diabetes mellitus and
      carotid endarterectomy for acute stroke. The approach was able to identify both
      the under-provision and over-provision of evidence-based effective services for
      stroke. This study has shown that an epidemiologically-based needs assessment
      could be a useful basis for the planning of health services.

PMID- 15841855
TI  - Do work-related breast cancer risks in pre-menopausal women depend on family
      history?
AB  - Our objective was to determine work-related pre-menopausal breast cancer risks
      that depend on a woman's family history of the disease. In a large case-control
      study, 318 women with breast cancer and 340 healthy women completed a mailed
      questionnaire. All of the women were pre-menopausal and controls were matched to
      cases by age. All risk estimates were adjusted for women's smoking history and
      whether they reported a prior breast biopsy. There was an odds ratio (OR) of 6.9
      (95% confidence interval: 1.5-31.9) for breast cancer among pre-menopausal women
      with no family history if they ever worked in material processing occupations.
      Among women with a family history of breast cancer, there was an OR of 6.4 (0.7
      55.9) if they ever worked as miscellaneous salesclerks and salespersons of
      commodities, and an OR of 5.7 (0.6-50.9) if they ever worked in department
      stores. Despite changes in the OR, none of the estimates were significantly
      different in women with and without a family history.

PMID- 15841856
TI  - Priming trait inferences through pictures and moving pictures: the impact of open
      and closed mindsets.
AB  - A newly developed paradigm for studying spontaneous trait inferences (STI) was
      applied in 3 experiments. The authors primed dyadic stimulus behaviors involving
      a subject (S) and an object (O) person through degraded pictures or movies. An
      encoding task called for the verification of either a graphical feature or a
      semantic interpretation, which either fit or did not fit the primed behavior.
      Next, participants had to identify a trait word that appeared gradually behind a
      mask and that either matched or did not match the primed behavior. STI effects,
      defined as shorter identification latencies for matching than nonmatching traits,
      were stronger for S than for O traits, after graphical rather than semantic
      encoding decisions and after encoding failures. These findings can be explained
      by assuming that trait inferences are facilitated by open versus closed mindsets
      supposed to result from distracting (graphical) encoding tasks or encoding
      failures (involving nonfitting interpretations).

PMID- 15841857
TI  - Violations of implicit theories and the sense of prediction and control:
      implications for motivated person perception.
AB  - Beginning with the assumption that implicit theories of personality are crucial
      tools for understanding social behavior, the authors tested the hypothesis that
      perceivers would process person information that violated their predominant
      theory in a biased manner. Using an attentional probe paradigm (Experiment 1) and
      a recognition memory paradigm (Experiment 2), the authors presented entity
      theorists (who believe that human attributes are fixed) and incremental theorists
      (who believe that human attributes are malleable) with stereotype-relevant
      information about a target person that supported or violated their respective
      theory. Both groups of participants showed evidence of motivated, selective
      processing only with respect to theory-violating information. In Experiment 3,
      the authors found that after exposure to theory-violating information,
      participants felt greater anxiety and worked harder to reestablish their sense of
      prediction and control mastery. The authors discuss the epistemic functions of
      implicit theories of personality and the impact of violated assumptions.

PMID- 15841858
TI  - Effects of motivational cues on perceptual asymmetry: implications for creativity
      and analytical problem solving.
AB  - In 4 experiments, participants were led to focus on either the prospect of
      positive outcomes (approach anticipation) or the prospect of negative outcomes
      (avoidance anticipation) and were subsequently administered behavioral measures
      of relative hemispheric activation. It was found that approach, relative to
      avoidance-related anticipatory states, produced greater relative right
      (diminished relative left) hemispheric activation. Experiment 3 additionally
      demonstrated that this pattern of activation was reversed when approach and
      avoidance states were not merely anticipatory but were also emotionally arousing.
      Finally, Experiment 4 replicated earlier findings demonstrating an influence of
      approach and avoidance anticipatory states on creativity and analytical problem
      solving (R. S. Friedman & J. Forster, 2001, 2003) and provided evidence that such
      effects are mediated by differences in relative hemispheric activation.

PMID- 15841859
TI  - Clearing the air: identity safety moderates the effects of stereotype threat on
      women's leadership aspirations.
AB  - Exposing participants to gender-stereotypic TV commercials designed to elicit the
      female stereotype, the present research explored whether vulnerability to
      stereotype threat could persuade women to avoid leadership roles in favor of
      nonthreatening subordinate roles. Study 1 confirmed that exposure to the
      stereotypic commercials undermined women's aspirations on a subsequent leadership
      task. Study 2 established that varying the identity safety of the leadership task
      moderated whether activation of the female stereotype mediated the effect of the
      commercials on women's aspirations. Creating an identity-safe environment
      eliminated vulnerability to stereotype threat despite exposure to threatening
      situational cues that primed stigmatized social identities and their
      corresponding stereotypes.

PMID- 15841860
TI  - Forgiveness and collective guilt assignment to historical perpetrator groups
      depend on level of social category inclusiveness.
AB  - The authors examined how categorization influences victimized group members'
      responses to contemporary members of a historical perpetrator group.
      Specifically, the authors tested whether increasing category inclusiveness--from
      the intergroup level to the maximally inclusive human level--leads to greater
      forgiveness of a historical perpetrator group and decreased collective guilt
      assignment for its harmdoing. Among Jewish North Americans (Experiments 1, 2, and
      4) and Native Canadians (Experiment 3) human-level categorization resulted in
      more positive responses toward Germans and White Canadians, respectively, by
      decreasing the uniqueness of their past harmful actions toward the in-group.
      Increasing the inclusiveness of categorization led to greater forgiveness and
      lessened expectations that former out-group members should experience collective
      guilt compared with when categorization was at the intergroup level. Discussion
      focuses on obstacles that are likely to be encountered on the road to
      reconciliation between groups that have a history of conflictual relations.

PMID- 15841861
TI  - Assortative mating and marital quality in newlyweds: a couple-centered approach.
AB  - Using a couple-centered approach, the authors examined assortative mating on a
      broad range of variables in a large (N = 291) sample of newlyweds. Couples showed
      substantial similarity on attitude-related domains but little on personality
      related domains. Similarity was not due to social homogamy or convergence. The
      authors examined linear and curvilinear effects of spouse similarity on self and
      observer indicators of marital quality. Results show (a) positive associations
      between similarity and marital quality for personality-related domains but not
      for attitude-related domains, (b) that similarity on attachment characteristics
      were most strongly predictive of satisfaction, (c) robust curvilinear effects for
      husbands but not for wives, (d) that profile similarity remained a significant
      predictor of marital quality even when spouses' self-ratings were controlled, and
      (e) that profile-based similarity indices were better predictors of marital
      quality than absolute difference scores.

PMID- 15841862
TI  - Putting the partner within reach: a dyadic perspective on felt security in close
      relationships.
AB  - The authors argue that felt insecurity in a partner's positive regard and caring
      stems from a specifically dyadic perception--the perception that a partner is out
      of one's league. A cross-sectional sample of dating couples revealed that people
      with low self-esteem feel inferior to their partner and that such feelings of
      relative inferiority undermine felt security in the partner's regard. Three
      experiments examined the consequences of reducing such perceived discrepancies by
      pointing to either strengths in the self or flaws in the partner. Low, but not
      high, self-esteem participants reacted to new strengths in the self or faults in
      the partner by reporting greater felt security in their specific partner's
      positive regard and commitment and more positive, general feelings about their
      own interpersonal worth. Thus, putting the partner more within the psychological
      grasp of low self-esteem people may effectively increase felt security in the
      partner's regard.

PMID- 15841863
TI  - Social network schemas and the learning of incomplete networks.
AB  - Social networks that are missing relations among some of their members--termed
      incomplete networks--have been of critical theoretical and empirical interest in
      sociological research on weak ties and structural holes but typically have been
      overlooked in social psychological studies of network learning. Five studies
      tested for schematic processing differences in the encoding and recalling of
      incomplete networks. In Studies 1 and 2, prior knowledge of missing relations
      facilitated learning an unfamiliar, incomplete network. Study 3 ruled out
      differences in general pattern recognition ability as an explanation. Study 4
      manipulated the degree of familiarity with missing relations, which produced
      predicted differences in learning rates. Finally, Study 5 examined how improved
      learning of an incomplete network affected a strategic organizational choice. The
      findings suggest that people can become schematic for complex, incomplete social
      networks.

PMID- 15841864
TI  - Interindividual-intergroup discontinuity as a function of trust and
      categorization: the paradox of expected cooperation.
AB  - Two experiments used a 3-choice variation of the prisoner's dilemma game to
      explore the paradoxical implications of expected cooperation of other groups and
      individuals for competitiveness and cooperativeness. Experiment 1 found that an
      experimental manipulation of opponent trustworthiness influenced the tendency of
      both groups and individuals to cooperate but had no significant effect on the
      tendency of groups and individuals to compete--possibly because of the perceived
      unfairness of competing with a trustworthy other. Experiment 2 found that an
      experimental manipulation of categorization increased the tendency of same
      category groups and individuals to cooperate (as in Experiment 1) and also
      increased the tendency of same-category groups, but not individuals, to compete
      (unlike in Experiment 1). It was further found that the tendency of same-category
      groups to compete more than same-category individuals was relatively stronger for
      participants high in guilt proneness.

PMID- 15841865
TI  - Socioeconomic status, resources, psychological experiences, and emotional
      responses: a test of the reserve capacity model.
AB  - The current study used ecological momentary assessment to test several tenets of
      the reserve capacity model (L.C. Gallo & K. A. Matthews, 2003). Women (N = 108)
      with varying socioeconomic status (SES) monitored positive and negative
      psychosocial experiences and emotions across 2 days. Measures of intrapsychic and
      social resources were aggregated to represent the reserve capacity available to
      manage stress. Lower SES was associated with less perceived control and positive
      affect and more social strain. Control and strain contributed to the association
      between SES and positive affect. Lower SES elicited greater positive but not
      negative emotional reactivity to psychosocial experiences. Women with low SES had
      fewer resources relative to those with higher SES, and resources contributed to
      the association between SES and daily experiences.

PMID- 15841866
TI  - Masculine girls and feminine boys: genetic and environmental contributions to
      atypical gender development in early childhood.
AB  - In this genetic study of atypical gender role development, parents of 5,799 twin
      pairs, ages 3 and 4, rated their twin children's masculinity and femininity. Boys
      were selected as gender atypical if they were highly feminine (top 5%, 10%, or
      15%) relative to other boys, and girls were selected if they were highly
      masculine relative to other girls. Gender-atypical boys and girls were each
      divided into 2 groups: fully gender atypical (e.g., feminine boys also low on
      masculinity) and partially gender atypical (e.g., feminine boys who are not low
      on masculinity). DeFries-Fulker (DF; J. C. DeFries & D. W. Fulker, 1985, 1988)
      extremes analysis yielded moderate group heritability and substantial shared
      environment effects for atypical gender role behavior. However, for fully gender
      atypical girls, group heritability accounted for most of the variance, and shared
      environment had no effect. The results are discussed in light of past studies and
      potential implications for atypical gender development.

PMID- 15841867
TI  - Is benzodiazepine use a risk factor for cognitive decline and dementia? A
      literature review of epidemiological studies.
AB  - BACKGROUND: A major public health issue is to determine whether long-term
      benzodiazepine use may induce cognitive deficits persisting after withdrawal. The
      aim of the present review was to examine findings from prospective studies
      carried out in general population samples exploring whether exposure to
      benzodiazepines is associated with an increased risk of incident cognitive
      decline. METHOD: Using a MEDLINE search and a hand-search of related references
      in selected papers, we retrieved original studies published in peer-reviewed
      journals that explored in general population samples the association between
      benzodiazepine exposure and change in cognitive performance between baseline and
      follow-up assessment. RESULTS: Six papers met the inclusion criteria. Two studies
      reported a lower risk of cognitive decline in former or ever users, two found no
      association whatever the category of user, and three found an increased risk of
      cognitive decline in benzodiazepine users. CONCLUSIONS: The discrepant findings
      obtained by studies examining the link between benzodiazepine exposure and risk
      of cognitive decline may be due to methodological differences, especially
      regarding the definitions of exposure and cognitive outcome. As a large
      proportion of subjects are exposed to benzodiazepines, a small increase in the
      risk of cognitive decline may have marked deleterious consequences for the health
      of the general population. This issue needs to be explored further by pharmaco
      epidemiological studies.

PMID- 15841868
TI  - Lifetime risk and persistence of psychiatric disorders across ethnic groups in
      the United States.
AB  - BACKGROUND: Recent research in the United States has demonstrated striking health
      disparities across ethnic groups. Despite a longstanding interest in ethnic
      disadvantage in psychiatric epidemiology, patterns of psychiatric morbidity
      across ethnic groups have never been examined in a nationally representative
      sample. METHOD: Ethnic differences in psychiatric morbidity are analyzed using
      data from the National Comorbidity Survey (NCS). The three largest ethnic groups
      in the United States--Hispanics, Non-Hispanic Blacks and Non-Hispanic Whites were
      compared with respect to lifetime risk and persistence of three categories of
      psychiatric disorder: mood disorder, anxiety disorder, and substance use
      disorder. RESULTS: Where differences across ethnic groups were found in lifetime
      risk, socially disadvantaged groups had lower risk. Relative to Non-Hispanic
      Whites, Hispanics had lower lifetime risk of substance use disorder and Non
      Hispanic Blacks had lower lifetime risk of mood, anxiety and substance use
      disorders. Where differences were found in persistence of disorders,
      disadvantaged groups had higher risk. Hispanics with mood disorders were more
      likely to be persistently ill as were Non-Hispanic Blacks with respect to both
      mood disorders and anxiety disorders. Closer examination found these differences
      to be generally consistent across population subgroups. CONCLUSIONS: Members of
      disadvantaged ethnic groups in the United States do not have an increased risk
      for psychiatric disorders. Members of these groups, however, do tend to have more
      persistent disorders. Future research should focus on explanations for these
      findings, including the possibility that these comparisons are biased, and on
      potential means of reducing the disparity in persistence of disorders across
      ethnic groups.

PMID- 15841869
TI  - Childhood physical and sexual abuse and subsequent depressive and anxiety
      disorders for two American Indian tribes.
AB  - BACKGROUND: This study examined the relationship of childhood abuse, both
      physical and sexual, with subsequent lifetime depressive and anxiety disorders-
      depression or dysthymia, post-traumatic stress disorder (PTSD), and panic or
      generalized anxiety disorder (GAD)--among American Indians (AIs). METHOD: Three
      thousand and eighty-four AIs from two tribes--Southwest and Northern Plains-
      participated in a large-scale, community-based study. Participants were asked
      about traumatic events and family history, and were administered standard
      diagnostic measures of depressive/anxiety disorders. RESULTS: Prevalence of
      childhood physical abuse was approximately 7% for both tribes. The Southwest
      tribe had higher prevalence of depressive and anxiety disorders, with rates of
      PTSD being the highest. Childhood physical abuse was significant in bivariate
      models of depressive/anxiety disorders, and remained so in the multivariate
      models. CONCLUSIONS: Childhood physical abuse was a significant predictor of all
      disorder groups for males in both tribes except for panic/GAD for the Northern
      Plains tribe in multivariate models; females showed a more varied pattern.
      Childhood sexual abuse did not significantly differ for males and females, and
      was an independent predictor of PTSD for both tribes, controlling for childhood
      physical abuse and other factors, and was significant for the other disorder
      groups only in the Southwest. Additional covariates that increased the odds of
      depressive/anxiety disorder, were adult physical or sexual victimization, chronic
      illness, lifetime alcohol or drug disorder, and parental problems with
      depression, alcohol, or violence. Results provided empirical evidence of
      childhood and later life risk factors and expanded the population at risk to
      include males.

PMID- 15841870
TI  - Community outreach for untreated schizophrenia in rural India: a follow-up study
      of symptoms, disability, family burden and costs.
AB  - BACKGROUND: In resource-poor countries, there remains an alarming treatment gap
      for people with schizophrenia, particularly those living in rural areas.
      Decentralization of mental health services, including community-based outreach
      programmes, represents one obvious strategy for bringing appropriate care to
      these communities. This study set out to assess the costs and effects of such a
      programme in rural Karnataka in India. METHOD: Eight rural communities were
      visited by an outreach team, who identified cases of drug-naive or currently
      untreated schizophrenia. Recruited cases were provided with appropriate
      psychotropic medication and psychosocial support, and after obtaining informed
      consent were assessed every 3 months over one and a half years on symptomatology,
      disability, family burden, resource use and costs. A repeated-measures analysis
      was carried out to test for significant change in these outcome measures over
      this period. RESULTS: A total of 100 cases of untreated schizophrenia were
      recruited, of whom 28% had never received antipsychotic medication and the
      remaining 72% had not been on medication for the past 6 months. Summary scores
      for psychotic symptoms, disability and family burden were all reduced
      significantly, with particular improvement observed at the first follow-up
      assessment. Increases in treatment and community outreach costs over the follow
      up period were accompanied by reductions in the costs of informal-care sector
      visits and family care-giving time. CONCLUSIONS: Efforts to organize community
      based care such as outreach services for people with schizophrenia living in more
      remote areas of resource-constrained countries can bring substantial benefits to
      patients and families alike.

PMID- 15841871
TI  - Psychopathology in the adolescent and young adult offspring of a community sample
      of mothers and fathers with major depression.
AB  - BACKGROUND: There is a large literature indicating that the offspring of mothers
      with Major Depressive Disorder (MDD) are at increased risk for depression.
      However, much less is known about the effects of paternal MDD on offspring
      psychopathology. METHOD: We addressed this issue using a large community sample
      of parents and their adolescent and young adult offspring (n = 775). Parents and
      offspring were independently assessed with semi-structured diagnostic interviews.
      Offspring were interviewed three times from mid-adolescence to age 24 years.
      RESULTS: Maternal MDD was significantly associated with offspring MDD. Paternal
      MDD was also significantly associated with MDD in offspring, but only among
      offspring with depressive episodes of moderate or greater severity. These effects
      persisted after controlling for socio-economic status, family intactness, and non
      mood disorders in both parents. Rates of MDD were particularly elevated in
      offspring of mothers and fathers with early-onset MDD, and offspring of fathers
      with recurrent MDD. The magnitude of the associations between MDD in parents and
      offspring was generally in the small-to-medium range. CONCLUSIONS: These results
      confirm previous findings of elevated risk of MDD in the offspring of depressed
      mothers. In addition, the results suggest that MDD in fathers is associated with
      increased risk of depression in offspring, but that it is limited to MDD episodes
      in offspring of moderate or greater severity.

PMID- 15841872
TI  - The changing impact of a severe disaster on the mental health and substance
      misuse of adolescents: follow-up of a controlled study.
AB  - BACKGROUND: Disasters are believed to have large effects on the mental health of
      adolescents but the lack of prospective pre- and post-disaster data on affected
      and control populations have limited our knowledge on the validity of these
      claims. We examined the medium-term, 12 months' effects of a severe disaster on
      the mental health of adolescents, and compared them to effects after 5 months.
      METHOD: A cafe fire in The Netherlands injured 250 adolescents and killed 14. We
      obtained data 15 months before and 12 months after the disaster about behavioural
      and emotional problems (using the Youth Self-Report) and substance misuse, in 124
      students of an affected school of whom 31 were present at the fire (response
      77.5%) and 830 other students (56.4%); mean age at baseline, 13.8 years. RESULTS:
      We found differences between students from the affected school and others for
      excessive use of alcohol (odds ratio 3.42, 95% confidence interval 2.00-5.85, p <
      0.0001), but not for behavioural and emotional problems and use of other
      substances. Effects had decreased compared to those after 5 months. CONCLUSIONS:
      In the long run, the effects of disaster decrease regarding self-reported
      behavioural and emotional problems, but they remain regarding alcohol misuse
      among those present at the disaster, and their peers.

PMID- 15841873
TI  - Female adolescents with anorexia nervosa and their parents: a case-control study
      of exercise attitudes and behaviours.
AB  - BACKGROUND: Few studies of physical activity in patients with anorexia nervosa
      (AN) have included a suitable control group. Nor has such research considered the
      influence of parents' activity on that of their children. Our first prediction
      was that adolescents with AN would be significantly more active than healthy
      controls both prior to, and during, the progression of their disorder. We also
      expected that the activity levels of parents and their daughters would be
      correlated, and that this relationship would be stronger in patient than control
      families. Finally, we expected that the AN parents would be more active and
      report a greater commitment to exercise than the control parents. METHOD: In a
      case-control design, we employed multiple indicators of physical activity from
      adolescent females and their parents, using longitudinal, retrospective, self
      report measurements. RESULTS: AN patients were significantly more active than
      controls both during the course of their disorder and prior to its onset.
      Parents' activity related to their daughter's activity, but this relationship was
      not stronger in the parents of the patients. CONCLUSIONS: Future research is
      needed to determine whether the relationship between parents' and children's
      activity levels reflects environmental or genetic influences, or a combination of
      both factors. The important observation of a significant increase in patients'
      activity levels at least a year prior to diagnosis of the disorder suggests that
      enhanced physical activity may play a role in the development of the disorder.
      This may also serve as an early warning sign of a subclinical eating disorder in
      adolescent girls.

PMID- 15841874
TI  - The stability of the Parental Bonding Instrument over a 20-year period.
AB  - BACKGROUND: The Parental Bonding Instrument (PBI) measures the perception of
      being parented to the age of 16 years. Low scores on the care dimension and high
      scores on the overprotection dimension are considered to be risk factors of
      depression. While the PBI has been shown to be a reliable and valid instrument,
      the stability of the PBI over extended periods (taking into account individual
      characteristics and life experience) needs to be demonstrated. METHOD: The PBI
      was measured in a non-clinical cohort on four waves between 1978 and 1998, along
      with a series of self-report measures including state depression and neuroticism.
      Differences in PBI change over time were examined by gender, lifetime major
      depression diagnosis, and life event variables, as well as by scores on
      neuroticism and state depression. RESULTS: Acceptable retest coefficients on PBI
      scores over the 20-year study were found for the cohort. No differences were
      found in PBI scores over time on the variables examined, including sex and
      depression measures. CONCLUSIONS: The results indicate long-term stability of the
      PBI over time. The influences of mood state and life experience appear to have
      little effect on the stability of the perception of parenting as measured by the
      PBI. The present study increases confidence in the PBI as a valid measure of
      perceived parenting over extended time periods.

PMID- 15841875
TI  - The construct of internalization: conceptualization, measurement, and prediction
      of smoking treatment outcome.
AB  - BACKGROUND: Depression symptoms and diagnoses are associated with failure to quit
      smoking in most studies, but not all. METHOD: A new measure of internalization
      (i.e. symptoms of depression or anxiety, or poor mood) was created to investigate
      whether internalization would predict smoking cessation in 549 smokers from three
      randomized clinical trials with inconsistent findings. RESULTS: Predicted item
      locations based on a map of the construct of internalization agreed with
      empirical locations based on item response theory. Internalization was highly
      correlated with neuroticism. Logistic regressions showed that internalization
      improved upon the predictions of other affect-related measures. High baseline
      internalization decreased abstinence from smoking at end of treatment and 3
      months thereafter. History of major depression (single-episode or recurrent)
      failed to predict abstinence. CONCLUSIONS: The broad, dimensional construct of
      internalization as conceptualized herein appears to be an important predictor of
      smoking cessation.

PMID- 15841876
TI  - Latent class typology of nicotine withdrawal: genetic contributions and
      association with failed smoking cessation and psychiatric disorders.
AB  - BACKGROUND: Nicotine withdrawal is associated with failed smoking cessation and
      thus contributes to continuance of the habit and increases risk of smoking
      related illnesses. Withdrawal is also associated with psychiatric disorders such
      as depression and alcoholism. However, relatively little is known about how to
      characterize the severity of withdrawal, including whether withdrawal subtypes
      exist in male smokers. If so, do these subtypes represent quantitative or
      qualitative differences? METHOD: Smoking and withdrawal data were obtained from
      4112 male-male twin pairs of the Vietnam Era Twin Registry during a 1992
      administration of the Diagnostic Interview Schedule. Latent Class Analysis (LCA)
      was used to derive significantly different nicotine withdrawal profiles, and
      their association with psychiatric disorders was assessed. Genetic and
      environmental contributions and the correlation between these contributions were
      evaluated using bivariate biometrical modeling of the withdrawal phenotype and
      failed smoking cessation. RESULTS: The LCA model which best fit the data was a
      four-class severity continuum. Psychiatric disorders were significantly
      associated with more severe classes and the magnitude of the association
      increased as withdrawal severity increased. Genetics accounted for 31% and 51% of
      the variance in risk for withdrawal and failed cessation, respectively. The
      genetic contributions were significantly correlated (r = 0.37). CONCLUSIONS:
      Nicotine withdrawal classes are characterized by quantitative differences. The
      strong association between psychiatric disorders and withdrawal severity and the
      significant genetic correlation between withdrawal and cessation highlight the
      importance of withdrawal severity. Further refinement of the DSM definition of
      withdrawal to incorporate severity ratings may be warranted.

PMID- 15841877
TI  - The severely mentally ill in residential facilities: a national survey in Italy.
AB  - BACKGROUND: In Italy, Residential Facilities (RFs) have completely replaced
      Mental Hospitals (MHs) for the residential care of mentally ill patients. We
      studied all patients resident in 265 randomly sampled Italian RFs (20% of the
      total). METHOD: Structured interviews focusing on each patient were conducted by
      trained research assistants with the manager and staff of each RF. Patients were
      rated with the HoNOS and the GAF, and comprehensive information about their
      sociodemographic and clinical status and care history were gathered. RESULTS: Of
      the 2962 patients living in the sampled facilities, most were males (63.2%) who
      had never married, more than 70% were over 40 years; 85% on a pension, most
      commonly because of psychiatric disability. A substantial proportion (39.8%) had
      never worked and very few were currently employed (2.5%); 45% of the sample was
      totally inactive, not even assisting with domestic activities in the facility.
      Two-thirds had a diagnosis of schizophrenia; co-morbid or primary substance abuse
      were uncommon. Twenty-one per cent had a history of severe interpersonal
      violence, but violent episodes in the RFs were infrequent. The managers judged
      almost three-quarters appropriately placed in their facilities and considered
      that very few had short-term prospects of discharge. CONCLUSIONS: Italian RFs
      cater for a large patient population of severely mentally ill requiring
      residential care. Discharge to independent accommodation is uncommon. Future
      studies should attempt to clarify how to match residential programmes with
      patients' disabilities.

PMID- 15841878
TI  - Early increase in vegetative symptoms predicts IFN-alpha-induced cognitive
      depressive changes.
AB  - BACKGROUND: The vegetative symptoms of depression resemble the symptoms of
      malaise associated with activation of the inflammatory response system (IRS), and
      can be regarded as an expression of a central motivational state that resets the
      organism's priorities to promote recovery from infection. Early vegetative
      symptoms, however, may also contribute to the high rates of depression seen later
      in the course of immune activation. We hypothesized that the onset of vegetative
      depressive symptoms early in the treatment with the pro-inflammatory cytokine IFN
      alpha in chronic hepatitis C patients would increase the risk for subsequent
      depressive cognitions. METHOD: Sixteen patients eligible for IFN-alpha treatment
      and free of psychiatric disorders were recruited. The DSM-IV, the
      Multidimensional Fatigue Inventory, and the Montgomery-Asberg Depression Rating
      Scale (MADRS) were administered at baseline and 1, 2, 4, 8, 12 and 24 weeks after
      treatment was initiated. Cognitive-depressive and vegetative-depressive symptom
      clusters were constructed. RESULTS: Fatigue and depression scores increased
      significantly during IFN-alpha treatment. Depression scores were highest at week
      8 of treatment. First week increase in vegetative-depressive symptom score
      predicted cognitive-depressive symptom score at week 8 and at week 24.
      CONCLUSIONS: During IFN-alpha treatment, vegetative symptoms of depression appear
      earlier than, and are predictive of, their cognitive counterparts. This finding
      suggests that low mood state may in part be driven by the increase in early
      vegetative-depressive symptoms in the course of IFN-alpha-induced immune
      activation.

PMID- 15841879
TI  - Stability of functional impairment in patients with schizotypal, borderline,
      avoidant, or obsessive-compulsive personality disorder over two years.
AB  - BACKGROUND: A defining feature of personality disorder (PD) is an enduring
      pattern of inner experience and behavior that is stable over time. Follow-up and
      follow-along studies have shown considerable diagnostic instability of PDs,
      however, even over short intervals. What, then, about personality disorder is
      stable? The purpose of this study was to determine the stability of impairment in
      psychosocial functioning in patients with four different PDs, in contrast to
      patients with major depressive disorder (MDD) and no PD, prospectively over a 2
      year period. METHOD: Six hundred treatment-seeking or treated patients were
      recruited primarily from clinical services in four metropolitan areas of the
      Northeastern USA. Patients were assigned to one of five diagnostic groups:
      schizotypal (STPD) (n=81), borderline (BPD) (n=155), avoidant (AVPD) (n=137), or
      obsessive-compulsive (OCPD) (n=142) personality disorders or MDD and no PD
      (n=85), based on the results of semi-structured interview assessments and self
      report measures. Impairment in psychosocial functioning was measured using the
      Longitudinal Interval Follow-up Evaluation (LIFE) at baseline and at three follow
      up assessments. RESULTS: Significant improvement in psychosocial functioning
      occurred in only three of seven domains of functioning and was largely the result
      of improvements in the MDD and no PD group. Patients with BPD or OCPD showed no
      improvement in functioning overall, but patients with BPD who experienced change
      in personality psychopathology showed some improvement in functioning. Impairment
      in social relationships appeared most stable in patients with PDs. CONCLUSION:
      Impairment in functioning, especially social functioning, may be an enduring
      component of personality disorder.

PMID- 15841880
TI  - Psychological morbidity related to the SARS outbreak in Hong Kong.

PMID- 15841881
TI  - Migraine: primary care challenges in diagnosis and treatment. Introduction.

PMID- 15841882
TI  - The epidemiology of migraine.
AB  - This article provides a review of the epidemiology and risk factors for migraine
      in population studies, as well as patterns for healthcare use. The burden and
      costs of migraine, as well as risk factors for disease progression, are also
      discussed. Although migraine is a remarkably common cause of temporary
      disability, many persons with migraine, even those with disabling headache, have
      never consulted a physician for the problem. Prevalence is highest in women, in
      persons between the ages of 25 and 55 years, and, at least in the United States,
      in individuals from lower income households. However, prevalence is high in
      groups other than these high-risk groups. In a subgroup of patients, migraine may
      be a progressive disorder.

PMID- 15841883
TI  - Identifying migraine in primary care settings.
AB  - Migraine disorders are largely unrecognized and untreated, despite the heavy
      burden they impose on individuals and society. Studies have shown that the
      symptom severity and disability associated with undiagnosed migraine are as
      burdensome as those associated with diagnosed migraine. Of those persons with
      migraine identified in population-based surveys, many were previously unaware
      that they had migraine. Furthermore, coexisting headache types and comorbid
      conditions contribute to misdiagnosis among those who consult a physician for
      headache. Patients who do seek medical attention for headaches usually visit
      their primary care providers. The purpose of this review is to highlight the
      distinguishing characteristics of migraine compared with other headache
      disorders, based on the new International Classification of Headache Disorders.
      To aid in diagnosis, simple screening tools, such as ID Migraine (Pfizer Inc.,
      New York, NY), are recommended. The clinical interview and headache diary aid in
      refining the diagnosis or suggesting the need for further evaluation. Improved
      recognition of migraine in primary care will increase the rate of successful
      treatment with effective migraine-specific therapies. This will result in
      improved functionality and decreased pain, and may help prevent disease
      progression.

PMID- 15841884
TI  - Initiating and optimizing acute therapy for migraine: the role of patient
      centered stratified care.
AB  - Migraine is a chronic, intermittently disabling condition that affects physical,
      mental, and social aspects of health-related quality of life. Because patients
      seeking assistance with migraine most often present to primary care providers,
      these healthcare professionals play critical roles in the diagnosis and treatment
      process. A comprehensive migraine management plan involves a partnership between
      the patient and healthcare professional where treatment goals and strategies are
      established. Elements of such a plan should include preventive strategies to
      reduce the frequency and effects of future attacks as well as the use of acute
      treatments to address the immediate need for relief during an attack. Approaches
      to prevention include education, lifestyle modification, and, often, appropriate
      medication. Many medications have been used for acute treatment. Nonspecific
      agents include nonsteroidal anti-inflammatory drugs (NSAIDs), single or
      combination analgesics (sometimes including antiemetics or caffeine), and
      narcotics. Migraine-specific medications include ergot alkaloids and triptans (5
      hydroxytryptamine(1B/1D) agonists). Various professional organizations have
      created guidelines to help providers in choosing appropriate management
      interventions. Clinical approaches to the patient with migraine include step
      care, whereby all patients begin on a simple or nonspecific treatment, stepping
      up to the next level of therapy if treatment is unsuccessful; or stratified care,
      whereby first-line therapy is tailored to the severity of the patient's pattern
      of headache. Studies have demonstrated that for more disabled headache patients,
      the stratified-care approach results in more robust headache response with less
      disability and greater cost-effectiveness than step care. Patient satisfaction
      studies demonstrate that the use of migraine-specific abortive medications
      (triptans) is associated with a higher satisfaction rate than over-the-counter
      preparations, NSAIDs, and analgesic combinations. Patients who initially reported
      satisfaction with the latter medications also reported a preference for triptan
      therapy. Healthcare professionals can assist patients, not only by choosing the
      most appropriate medication but also by assessing whether the level of benefit
      the patient is currently receiving could be improved.

PMID- 15841885
TI  - Evaluating the triptans.
AB  - The debilitating effect of migraine has fueled the search for more specific
      agents to treat its characteristic and associated symptoms. Second-generation
      oral triptans have shown an improved efficacy profile in comparison with the
      pioneer sumatriptan and with the over-the-counter medications and prescription
      analgesics that have been staples of migraine treatment. Although all triptans
      exert effects through the 5-hydroxytryptamine 1B/1D receptors, each triptan has
      distinctive pharmacokinetic properties that determine its efficacy and
      tolerability profile. Empirical findings based on clinical trials have led to
      associations between triptan pharmacology and efficacy. With the expanded
      treatment choices, the onus is on healthcare providers (especially primary care
      physicians, who see the majority of patients with migraine) to determine which
      treatment has an efficacy profile that best suits the individual patient's needs.
      Patients prefer pharmacotherapy with a rapid onset of action that facilitates
      complete pain relief and no recurrence. Data from published comparator trials,
      based on commonly used efficacy end points and pharmacokinetic properties
      underlying patient-preferred outcomes, are reviewed in this article.

PMID- 15841886
TI  - Evaluating the safety and tolerability profile of acute treatments for migraine.
AB  - Among the medications that have been used as acute treatments for migraine are
      nonspecific agents, including nonsteroidal anti-inflammatory drugs (NSAIDs),
      analgesics (either single or combination), and narcotics, as well as migraine
      specific medications, including ergot alkaloids and triptans (5-hydroxytryptamine
      1B/1D agonists). All of these drugs have side effects that vary in type and
      severity. Side effects of nonspecific medications, including gastrointestinal
      (GI) and renal effects with NSAIDs and cognitive effects and the potential for
      abuse with narcotics and butalbital-containing medications, have been documented
      over time, as these medications have been used for various indications. Side
      effects of the migraine-specific medications include GI and vascular symptoms
      with the ergots; for the triptans, they include chest and neurologic symptoms.
      Although adverse events are reported fairly frequently in patients receiving
      triptans, they are usually mild, and few patients discontinue therapy because of
      them. The most serious adverse events are cardiovascular. Because of potential
      vasoconstrictor effects--mild and transient increases in blood pressure and mild
      and transient effects on coronary artery tone--triptans as a class are
      contraindicated in patients with established or clinically suspected
      cardiovascular disease, specifically ischemic heart disease and uncontrolled
      hypertension. Other adverse events, including the potential for drug-drug
      interactions, are less common. Therefore, consideration should be given to the
      tolerability and safety of medications before their use as abortive medications
      for the treatment of migraine headache.

PMID- 15841887
TI  - Conclusion: how primary care physicians can help their patients with migraine.

PMID- 15841888
TI  - Probabilistic analysis of cost-effectiveness models: statistical representation
      of parameter uncertainty.

PMID- 15841889
TI  - Growth and quality of the cost-utility literature, 1976-2001.
AB  - PURPOSE: Cost-utility analyses (CUAs) have become increasingly popular, although
      questions persist about their comparability and credibility. Our objectives were
      to: 1) describe the growth and characteristics of CUAs published in the peer
      reviewed literature through 2001; 2) investigate whether CUA quality has improved
      over time; 3) examine whether quality varies by the experience of journals in
      publishing CUAs, or the source of external funding for study investigators; and
      4) examine changes in practices in US-based studies following recommendations of
      the US Panel on Cost-Effectiveness in Health and Medicine (USPCEHM). This study
      updates and expands our previous work, which examined CUAs through 1997. METHODS:
      We conducted a systematic search of the English-language medical literature for
      original CUAs published from 1976 through 2001, using Medline and other
      databases. Each study was audited independently by two trained readers, who
      recorded the methodological and reporting practices used. RESULTS: Our review
      identified 533 original CUAs. Comparing articles published in 1998 to 2001 (n =
      305) with those published in 1976 to 1997 (n = 228), studies improved in almost
      all categories, including: clearly presenting the study perspective (73% vs. 52%,
      P < 0.001); discounting both costs and quality-adjusted life-years (82% vs. 73%,
      P = 0.0115); and reporting incremental cost-utility ratios (69% vs. 46%, P <
      0.001). The proportion of studies disclosing funding sources did not change (65%
      vs. 65%, P = 0.939). Adherence to recommended practices was greater in more
      experienced journals, and roughly equal in industry versus non-industry-funded
      analyses. The data suggest an impact in methodological practices used in US-based
      CUAs in accordance with recommendations of the USPCEHM. CONCLUSIONS: Adherence to
      methodological and reporting practices in published CUAs is improving, although
      many studies still omit basic elements. Medical journals, particularly those with
      little experience publishing cost-effectiveness analyses, should adopt and
      enforce standard protocols for conducting and reporting CUAs.

PMID- 15841890
TI  - Variability of cost-effectiveness estimates for pharmaceuticals in Western
      Europe: lessons for inferring generalizability.
AB  - OBJECTIVES: It has long been suggested that, whereas the results of clinical
      studies of pharmaceuticals are generalizable from one jurisdiction to another,
      the results of economic evaluations are location dependent. There has been,
      however, little study of the causes of variation, whether differences in study
      results among countries are systematic, or whether they are important for
      decision making. METHODS: A literature search was conducted to identify economic
      evaluations of pharmaceuticals conducted in two or more European countries. The
      studies identified were then classified by methodological type and analyzed to
      assess their level of variability and to identify the main causes of variation.
      Assessments were also made of the extent to which differences in study results
      among countries were systematic and whether they would lead to a different
      decision, assuming a range of values of the threshold willingness-to-pay for a
      life-year or quality-adjusted life-year (QALY). RESULTS: In total 46 intercountry
      drug comparisons were identified, 29 in multicountry studies and 17 in comparable
      single country studies that were considered to be sufficiently similar in terms
      of methodology. The type of study (i.e., trial-based or modeling study) had some
      impact on variability, but the most important factor was the extent of variation
      across countries in effectiveness, resource use or unit costs, allowed by the
      researcher's chosen methodology. There were few systematic differences in study
      results among countries, so a decision maker in country B, on seeing a recent
      economic evaluation of a new drug in country A, would have little basis on which
      to predict whether the drug, if evaluated, would be more or less cost-effective
      in his or her country. Given the extent of variation in cost-effectiveness
      estimates among countries, the importance of this for decision making depends on
      decision makers' thresholds in willingness-to-pay for a QALY or life-year. If a
      cost-effectiveness threshold (i.e., willingness-to-pay) for a life-year or QALY
      of dollar 50,000 were assumed, the same conclusion regarding cost-effectiveness
      would be reached in most cases. CONCLUSION: This review shows that cost
      effectiveness results for pharmaceuticals vary from country to country in Western
      Europe and that these variations are not systematic. In addition, constraints
      imposed by analysts may reduce apparent variability in the estimates. The lessons
      for inferring generalizability are not straightforward, although the implications
      of variation for decision making depend critically on the cost-effectiveness
      thresholds applying in Western Europe.

PMID- 15841891
TI  - An evaluation of managing and educating patients on the risk of glucocorticoid
      induced osteoporosis.
AB  - OBJECTIVE: To assess the impact of risk management activities on patient risk of
      glucocorticoid-induced osteoporosis. METHODS: Ninety-six adult patients taking
      chronic glucocorticoid therapy in 15 community pharmacies. Patients in the
      control group received usual and customary care. Patients in the treatment
      pharmacies received education and an educational pamphlet about the risks of
      glucocorticoid-induced osteoporosis. In addition, the treatment group pharmacists
      monitored the patients' drug therapy, to identify and address drug-related
      problems. Data including the glucocorticoid taken by the patient, medications,
      and osteoporosis risk factors were collected at baseline and after 9 months of
      monitoring, via Web-based survey completed in the pharmacy. Using an intent to
      treat approach, the pre-post frequency changes were compared with contrasts for
      presence of bisphosphonate therapy, presence of estrogen therapy, presence of
      calcium supplement, discussion of glucocorticoid-induced osteoporosis risk,
      discussion of bone density test, presence of bone mineral density test, reported
      inactivity, and reported low calcium diet. RESULTS: The contrast was significant
      in favor of the treatment pharmacies for the frequency of patients taking a
      calcium supplement (Control [-6.9%] vs. Treatment [17.1%], P < 0.05). No other
      contrast was significant. CONCLUSIONS: Community pharmacists are capable of
      increasing calcium supplementation among patients at risk for glucocorticoid
      induced osteoporosis. Pharmacists who educate at-risk patients can impact the
      self-care of these patients.

PMID- 15841892
TI  - Probabilistic Markov model to assess the cost-effectiveness of bronchodilator
      therapy in COPD patients in different countries.
AB  - OBJECTIVES: The development of a probabilistic Markov model with a time horizon
      of 1 year to compare the cost-effectiveness of three bronchodilators: 1) the new
      long-acting anticholinergic tiotropium; 2) the short-acting anticholinergic
      ipratropium; and 3) the long-acting beta 2-agonist salmeterol, for the treatment
      of patients with chronic obstructive pulmonary disease (COPD) in different
      countries. In this article we compare The Netherlands and Canada. METHODS: The
      Markov model was structured along disease severity states and exacerbations.
      Transition probabilities between disease states and exacerbation probabilities
      were derived from patient-level data from six randomized controlled trials
      assessing the efficacy and safety of tiotropium. Resource utilization during
      exacerbations and maintenance treatment for The Netherlands were derived from two
      clinical trials, whereas for Canada these data were obtained from a countrywide
      observational study that used similar inclusion criteria as the trials. Second
      order Monte Carlo simulations were undertaken in which values were randomly drawn
      from distributions of these parameters. Outcomes of the model are yearly
      treatment costs, exacerbations, and quality-adjusted life months. RESULTS: The
      mean difference in the number of exacerbations was 0.17 (95% uncertainty
      interval: -0.02-0.37) in favor of tiotropium when compared with salmeterol and
      the difference between salmeterol and ipratropium was 0.12 (-0.17-0.44) in favor
      of salmeterol. The number of quality-adjusted life months did not substantially
      differ between treatment groups and varied from 8.42 (SE 0.41) in the tiotropium
      group to 8.17 (0.46) in the salmeterol group and 8.11 (0.50) in the ipratropium
      group. In The Netherlands, costs in the tiotropium group were 42 Euros (-484-353)
      lower than in the salmeterol group, whereas costs in the salmeterol group were
      128 Euros (-795-457) lower than in the ipratropium group. In Canada, costs were
      consistently lower than in The Netherlands and nearly the same in all treatment
      groups. Differences between the two countries were primarily a result of a higher
      length of hospital stay in case of an exacerbation in The Netherlands. The cost
      effectiveness acceptability frontier of exacerbations showed that tiotropium was
      associated with the maximum expected net benefit for all values of the ceiling
      ratio above 0 Euros (The Netherlands) and 10 Euros (Canada) in the base case
      analysis. CONCLUSIONS: This probabilistic model-based economic evaluation
      demonstrates how clinical trial data can be combined and integrated with country
      specific information about resource utilization and unit cost to assess the cost
      effectiveness of bronchodilators in COPD patients. Quality-adjusted life months
      did not substantially differ between treatment groups. In terms of exacerbations,
      tiotropium was associated with maximum expected net benefit for plausible values
      of the ceiling ratio. In sensitivity analyses, this outcome was most sensitive to
      changes in exacerbation rates.

PMID- 15841893
TI  - Effect of outpatient treatment of febrile neutropenia on the risk threshold for
      the use of CSF in patients with cancer treated with chemotherapy.
AB  - OBJECTIVES: Febrile neutropenia (FN) in patients with cancer treated with
      chemotherapy has traditionally been managed with inpatient broad-spectrum
      antibiotics until the infection and neutropenia have resolved. A newer strategy
      is outpatient oral or intravenous antibiotics in selected patients after an
      initial hospitalization. We sought to determine these costs, both overall and
      relative to those of traditional management, and the optimal role of prophylactic
      colony-stimulating factor (CSF) in patients at greatest risk for FN. METHODS:
      Existing economic decision models were modified by incorporating a treatment
      strategy for FN in which patients are classified as high- and low-risk according
      to criteria described by Talcott. Low-risk patients were assumed to be treated as
      outpatients. Overall costs with the revised economic model were assessed and
      sensitivity analyses were performed. RESULTS: The costs of an episode of FN were
      estimated as 1) no CSF: dollar 13,355; 2) CSF with hospitalization for FN: dollar
      8677; and 3) CSF with risk stratification and outpatient management in low-risk
      patients: dollar 8188. The risk threshold for the cost-effective use of CSF was
      only slightly lower with outpatient treatment. When all patients with FN are
      treated as inpatients and the cost of hospitalization is dollar 1750/day the risk
      threshold for FN at which prophylactic CSF becomes cost-effective is 16%. It is
      15% when low-risk patients are treated as outpatients. CONCLUSIONS: Outpatient
      treatment slightly decreases the risk threshold for FN at which prophylactic CSF
      becomes cost-effective. The limited economic effect of this strategy may be
      because the patients who were at greatest risk of complications had significantly
      longer lengths of stay and accounted for most of the hospitalization costs.

PMID- 15841894
TI  - An assessment of the impact of informative dropout and nonresponse in measuring
      health-related quality of life using the EuroQol (EQ-5D) descriptive system.
AB  - OBJECTIVES: To investigate the impact of imputing EQ-5D values to allow for
      informative dropout and nonresponse in a longitudinal assessment of the health
      related quality of life (HRQL) of liver transplant recipients. METHODS: The EQ-5D
      was administered at defined time intervals pre- and post-transplantation to all
      adults who were listed to receive liver transplants as National Health Service
      (NHS) treatment at each of the six Department of Health designated centers in
      England and Wales over a time-period of 36 months (12 month recruitment period
      and 24 month follow-up period). During the course of the study missing data arose
      for two main reasons, informative dropout and nonresponse. Informative dropout
      was accounted for by giving those patients who died an EQ-5D score of 0 and those
      patients who were too ill to respond to an EQ-5D score equivalent to the 5th
      percentile of respondents for each time point pretransplantation. Nonresponse was
      accounted for using relatively naive approaches (last value carried forward, and
      upper/lower 95% confidence interval around the mean) and contrasted with a more
      sophisticated multiple imputation method. RESULTS: Adjusting for informative
      dropout in isolation resulted in a marked deterioration in mean scores over time
      pretransplant relative to the base case situation in which no such adjustments
      were made. Nevertheless, adjusting for informative dropout and/or nonresponders
      did not alter the base case conclusion of no statistically significant
      differences in mean EQ-5D scores over time pretransplant. In contrast, post
      transplant data indicated highly statistically significant improvements in
      quality of life over time for the base case (P < 0.001) whereas no statistically
      significant improvements over time were found when informative dropout was
      allowed for in isolation (P = 0.402) or when informative dropout and nonresponse
      were allowed for simultaneously (P = 0.105-0.185). CONCLUSIONS: It is important
      that future studies which purport to assess the HRQL over time of patients, such
      as these with end-stage liver disease, include an allowance for informative
      dropout and nonresponse within the analysis.

PMID- 15841895
TI  - Development and initial validation of an instrument to measure physician
      pharmacist collaboration from the physician perspective.
AB  - OBJECTIVE: Using a conceptual model of collaborative working relationships
      between pharmacists and physicians, a measure for physician-pharmacist
      collaboration from the physician perspective was developed. The measure was
      analyzed for its factor structure, internal consistency, construct validity, and
      other psychometric properties. METHODS: An initial 27-item Physician-Pharmacist
      Collaboration Instrument (PPCI) was developed to assess seven themes about
      professional relationships using Likert scales. The PPCI was mailed to a random
      sample of 1000 primary care physicians. Principal component analysis was used to
      assess the structure and uncover underlying dimensions of the initial instrument.
      Items were evaluated for inclusion or exclusion into a refined instrument.
      Internal consistency was assessed by calculating Alpha coefficients for each
      identified factor. Convergent validity was assessed using Spearman correlations
      between the identified factors and a previous measure of collaborative care.
      After measure refinement, confirmatory factor analysis was used to evaluate the
      fit of both versions of the instrument. RESULTS: Three hundred forty usable
      surveys were returned for a response rate of 34%. Almost 70% of the respondents
      were male with a mean age of 45.8. A majority were family practice physicians
      (72.1%) in private practice (67.3%). Three unique factors were identified during
      principal component analysis and utilized in a confirmatory factor analysis. Both
      a full and a 14-item reduced model were constructed and tested. Cronbach's alpha
      for the three factors of the full model ranged from 0.91 to 0.97, while the
      reliability for the reduced model ranged from 0.86 to 0.96. Comparative fit
      indexes of 0.97 and 0.98 were obtained, indicating good fit for the models.
      CONCLUSIONS: The results indicate good reliability and validity of the refined
      (14-item) PPCI. This instrument can be useful as a research tool for assessment
      of the physicians' perspective about a physician-pharmacist relationship. Further
      research is warranted to examine if the extent of relationship development, as
      measured with the PPCI, can affect patient care outcomes.

PMID- 15841896
TI  - Collection of health-economic data alongside clinical trials: is there a future
      for piggyback evaluations?
AB  - OBJECTIVE: The objective of this article is to discuss issues surrounding the
      conduct of "piggyback evaluations," in which health-economic data are collected
      within an otherwise typical clinical trial. METHODS: We review the methodologic
      literature on piggyback economic evaluations, as well as selected empiric
      studies. We summarize the challenges encountered in the conduct of these studies,
      alternative ways of addressing these challenges, and their future role in
      pharmacoeconomic research. RESULTS: Piggyback evaluations have certain advantages
      over other types of pharmacoeconomic studies. An economic evaluation can benefit
      from the experimental design that maximizes the trial's internal validity, and it
      is often more practical to collect economic data alongside a trial rather than to
      fund a stand-alone economic study. However, piggyback evaluations are subject to
      problems deriving from the competing nature of clinical versus economic study
      objectives, which can give rise to tension in such fundamental aspects of study
      design as the selection of study subjects and sites; the extent of protocol
      mandated health-care services; and the determination of sample size, length of
      follow-up, and the study comparator(s). Many solutions have been put forth in the
      literature to address these challenges. CONCLUSIONS: Piggyback evaluations can be
      an appropriate means to measure the economic impact of medical interventions,
      provided that the methodologic challenges are acknowledged and addressed within
      the context of each individual study. As long as a desire for patient-level data
      from clinical trials exists, there will be a need for piggyback economic
      evaluations in the future.

PMID- 15841897
TI  - Some considerations for the interpretation of health-related quality of life
      data.

PMID- 15841898
TI  - Needs-based health-related quality of life measurement: new wine in old bottles?

PMID- 15841899
TI  - Thresholds in cost-effectiveness analysis--more of the story.

PMID- 15841900
TI  - Acetylcholinesterase and butyrylcholinesterase--important enzymes of human body.
AB  - The serine hydrolases and proteases are a ubiquitous group of enzymes that is
      fundamental to many critical life-functions. Human tissues have two distinct
      cholinesterase activities: acetylcholinesterase and butyrylcholinesterase.
      Acetylcholinesterase functions in the transmission of nerve impulses, whereas the
      physiological function of butyrylcholinesterase remains unknown.
      Acetylcholinesterase is one of the crucial enzymes in the central and peripheral
      nerve system. Organophosphates and carbamates are potent inhibitors of serine
      hydrolases and well suited probes for investigating the chemical reaction
      mechanism of the inhibition. Understanding the enzyme's chemistry is essential in
      preventing and/or treating organophosphate and carbamate poisoning as well as
      designing new medicaments for cholinergic-related diseases like as Alzheimer's
      disease.

PMID- 15841901
TI  - Natal and neonatal teeth.
AB  - Tooth eruption follows a chronology corresponding to the date when the tooth
      erupts into the oral cavity. This date has been established in the literature and
      is subject to small variations depending on hereditary, endocrine and
      environmental features. Any disturbance during the development of the teeth 
      systemic or local- can affect not only the morphology, structure of dental hard
      tissues or number of teeth but also the time of eruption. The presence of a tooth
      in the mouth at birth or during the first month of life has been studied and
      denominated as natal and neonatal teeth. The aim of this paper is to review
      current information on this topic and to give treatment alternatives if it is
      necessary.

PMID- 15841902
TI  - Subependymal zone: immunohistochemically distinct compartment in the adult
      mammalian forebrain.
AB  - The subependymal zone (SEZ) lining lateral walls of the lateral cerebral
      ventricles represents the site of active neurogenesis in the brain of adult
      mammals. Peroxidase immunohistochemistry performed in paraffin-embedded sections
      reveals that structural organization of the SEZ differs from other regions in the
      brain. The SEZ is devoid of synapses that are abundant in the adjacent striatal
      neuropil. Therefore immunostaining of synaptophysin detects sharp borders of the
      SEZ. Using immunophenotypization, we identified cell types constituting the SEZ
      in the intact rat forebrain. The presence of neural progenitor/stem cells was
      confirmed by finding of nestin-immunopositive cells. Detection of the astroglial
      marker GFAP confirmed that astrocytes represented major supporting elements
      responsible for creating a unique microenvironment of the SEZ. One type of the
      astroglia participated in covering surfaces of the blood vessels and boundaries
      of the SEZ. The second astroglial cell type formed branched elongated tubes that
      enwrapped other SEZ cell types with their cytoplasmic extensions. The interior of
      astrocytic channels was occupied with small densely aggregated NCAM
      immunoreactive neuroblasts. Bipolar morphology indicated that these cells
      probably underwent migration. Immunodetection of other neuronal markers like beta
      III tubulin, MAP-2 and Pan neurofilaments identified positive cells in the
      neighbouring brain parenchyma but not in the SEZ. The rostral migratory stream
      (RMS) linked with the anterior SEZ had a similar structural arrangement. It
      contained a large amount of nestin+ and vimentin+ cells. The RMS consisted of
      GFAP+ astrocytic tubes ensheathing NCAM+ neuroblasts. On the contrary to the SEZ,
      the RMS neuroblasts expressed beta-III tubulin. However, markers of postmitotic
      neurons MAP-2, Pan neurofilaments and synaptophysin were not expressed in the
      RMS. Our study describes a complex histological structure of the rat SEZ,
      identifies its individual cell types and demonstrates a usefulness of
      immunohistochemical detection of cell-specific markers in a study of
      microenvironment forming neurogenic zones in the mammalian brain.

PMID- 15841903
TI  - Passivation of dental amalgams and mercury release.
AB  - OBJECTIVES: In this study the rate of dissolution of mercury from two dental
      amalgams with different compositions and structures was determined in vitro under
      different oxidation and abrasion conditions, and the results were correlated with
      the electrochemical characteristics. METHODS: A spherical high copper and a lathe
      cut very high-copper amalgam were tested in aerated and deaerated artificial
      saliva. The electrochemical characteristics were determined by potential-time,
      anodic polarization, polarization resistance and cathodic stripping measurements.
      Mercury release tests were performed after either stabilization in the solution,
      or abrasion using SiC papers or rotary toothbrush, with or without toothpaste.
      Dissolved mercury was determined by atomic absorption spectrophotometry. RESULTS:
      Both amalgams exhibited passivation, the amalgam with the higher copper content
      passivating spontaneously even when the oxygen content in the solution was
      minimized. At a higher oxygen content in the solution the rate of mercury release
      from the amalgams was lower than when the oxygen content was minimized, and
      decreased further after a pre-exposure. Brushing generally increased the release.
      SIGNIFICANCE: The results show the importance of the oxidation conditions and
      passivation characteristics of dental amalgams for mercury release, especially in
      the transient state after abrasion by chewing or tooth brushing.

PMID- 15841904
TI  - Therapeutic efficacy of different antidotal mixtures against poisoning with GF
      agent in mice.
AB  - The toxicity of cyclohexyl methylphosphonofluoridate (GF-agent; cyclosarin) and
      therapeutic efficacy of four oximes (trimedoxime, methoxime, obidoxime and HI-6)
      in combination with atropine or benactyzine (BNZ) was studied in mice. The oxime
      therapy combined with anticholinergic drug was administered intramusculary (i.m.)
      1 or 2 min after i.m. GF-agent challenge. All the drugs were applied in dose of
      20% of LD50. Obidoxime and trimedoxime that were combined with atropine were less
      effective than methoxime and HI-6 in combination with BNZ when applied 2 minutes
      after GF-agent poisoning. When the drugs were administered 1 min after GF-agent
      challenge already, in case of methoxime, the faster application of therapy
      resulted in significantly higher protective ratio, while for obidoxime the
      therapeutic effectivity did not depend significantly on the seasonableness of
      therapeutic intervention. The present findings show that all four combinations of
      oxime with anticholinergic drug decrease the GF-agent toxicity more than twofold
      regardless of the time of treatment administration.

PMID- 15841905
TI  - What are the reactivities of coronary arteries harvested from the hearts exposed
      to cold ischemic preservation?
AB  - This study was designed to determine the effects of pretransplant ischemic
      hypothermic period on reactivities of major coronary arteries. Eleven pigs were
      used. Right, left anterior descending and circumflex coronary arteries harvested
      from 6 pigs following single dose of cardioplegia and cardiectomy. The same
      procedures were performed in 5 pigs after 6 hours static 4 degrees C hypothermic
      preservation of the hearts. Strips prepared from these 3 coronary arteries were
      placed in organ chambers and contractions with acetylcholine and histamine and
      KCL and dilatations with noradrenaline following submaximal contractions with
      acetylcholine and histamine were documented. There was no statistically
      significant difference between results taken from both groups. The pretransplant
      period (until 6 hours) does not cause important differences on the reactivities
      of coronary arteries.

PMID- 15841906
TI  - Correlation of serum magnesium with dyslipidemia in maintenance hemodialysis
      patients.
AB  - One of the factors involved in accelerated atherosclerosis in hemodialysis
      patients is dyslipidemia. In this study we considered factors involved in
      intensification of dyslipidemia in hemodialysis patients. This study was done on
      36 maintenance hemodialysis patients. Serum lipoprotein (a), Triglyceride,
      Cholesterol, HDL-C,LDL-C and also serum Intact parathormone(iPTH), Calcium,
      Phosphorus, Magnesium were measured. In statistical analysis there was not any
      correlation between serum lipids and iPTH. There was not correlation between
      serum calcium with serum lipids (p > 0.05). There was not correlation between
      CaxP product with serum lipids (p > 0.05). There was a positive correlation
      between serum Magnesium and Lipoprotein(a) (P < 0.05) and also positive
      correlation between serum magnesium with triglyceride level (P < 0.05) was seen
      too. Magnesium doesn't increase the lipoprotein synthesis. It may involve in the
      regulation of some enzymes responsible for lipoprotein synthesis. Correlation of
      serum magnesium with serum triglycerides can be due to changes in hepatic
      triglyceride metabolism. Lipoprotein(a) is a non traditional factor of premature
      atherosclerosis, its association with serum magnesium needs more attention in
      hemodialysis patients.

PMID- 15841907
TI  - Our experience with diagnostics of congenital disorders of glycosylation.
AB  - The aim of this study is to report our 3years experience with the screening of
      congenital disorders of glycosylation. A common isoelectric focusing method with
      immunofixation was used for analysis of serum transferrin and alpha1-antitrypsin,
      apart from several other procedures. A group of about 1000 individuals, both
      healthy controls and patients, mostly with signs of a metabolic disease were
      examined. Here we present an overview of (1) hypoglycosylation findings, (2)
      distribution of protein variants, (3) misguiding rare Tf variants found in our
      set, and (4) association of some phenotypes with various diseases.

PMID- 15841908
TI  - The impairment of gastroduodenal mucosal barrier by coffee.
AB  - BACKGROUND: Even though coffee is not considered to be responsible for
      development of peptic ulcer, it may, however, prolong its healing by increasing
      acidity of gastric content. In our former work we observed a profound increase in
      sucrose permeability (above normal values) in healthy volunteers regularly
      drinking coffee for years. In literature, many factors affecting sucrose
      permeability have been described so far. None of them, however, studied the
      effect of coffee. SUBJECTS, MATERIALS AND METHODS: 10 young asymptomatic habitual
      coffee drinkers were included in the study. The probands underwent SaLM test
      twice--first time without coffee restriction and second time after 48-hour coffee
      abstinence. The ingested SaLM solution comprised sucrose (25.0 g), lactulose
      (10.0 g), mannitol (2.0 g), xylose (2.0 g) and water (up to 100 ml). Urine was
      collected for five hours and the samples were analysed using gas chromatography.
      Results were compared with those of 8 young healthy volunteers not drinking
      coffee. Permeability for sucrose was significantly higher in the group of
      habitual coffee drinkers in comparison with non-coffee drinkers (p < 0.01). After
      48-hour coffee abstinence sucrose excretion decreased significantly (p < 0.05) to
      a level not differing from that of non-coffee drinkers (p = 0.54). CONCLUSIONS:
      Our results indicate that coffee may damage gastroduodenal mucosa in habitual
      coffee drinkers. In a time period of 48 hours the gastroduodenal mucosa is
      capable of a significant regeneration.

PMID- 15841909
TI  - Calciphylaxis involving both the upper and lower extremities.
AB  - Calciphylaxis is an uncommon complication of end stage renal disease (ESRD) and
      secondary hyperparathyroidism. It characterized by cutaneous necrosis with mural
      calcifications and thrombosis in the small vessels of dermis. It is important to
      diagnose and treat, because of mortality rate from calciphylaxis is very high. We
      present the case of a patient with ESRD and type II diabetes mellitus developing
      calciphylaxis of the both upper and lower extremities had normal corrected
      calcium-phosphate product level. After amputation, necrosis was showed rapid
      progression resulting in death in one month.

PMID- 15841910
TI  - Acute stomach volvulus--case report.
AB  - Stomach volvulus in its acute form is a serious sudden disorder in the abdominal
      cavity. The case of stomach volvulus, that had been successfully surgically
      solved, is described in the presented paper. Even though the volvulus was not
      caused by the hiatus hernia, the antireflux fundoplication according to Nissen
      Rossetti was performed besides the frontal gastropexy.

PMID- 15841911
TI  - Iron deposition in the brain following the ischemia in a rat model of ischemic
      tolerance.
AB  - Preconditioning of the brain by short-term ischemia increases brain tolerance to
      the subsequent severer ischemia. In this study, we investigated iron deposition
      in the cerebral cortex and the ischemic tolerance in a rat model of cerebral
      ischemia. Forebrain ischemia was induced by four-vessel occlusion for 5 min as
      ischemic preconditioning. Two days after preconditioning or after the sham
      operation, the second ischemia was induced for 20 min. Changes in the cerebral
      cortex were examined after 1 to 8 weeks of recirculation following 20 min
      ischemia with or without preconditioning using the iron histochemistry. Granular
      deposits of the iron were found in the cytoplasm of the pyramidal cells in the
      layers III and V of the frontal cortex after 1 week of recirculation. When the
      rats were exposed to 5 min ischemia 2 days before 20 min lasting ischemia, the
      deposition of iron in the cytoplasm of the pyramidal cells in layers III and V of
      the frontal cortex was significantly lower during all periods of reperfusion.
      Preconditioning 5 min ischemia followed by 2 days of reperfusion before 20 min
      ischemia also prevented degeneration of the pyramidal neurons in layers III and V
      of the frontal cortex.

PMID- 15841912
TI  - Theoretical basis of new methodology of mathematical-statistical decision making
      with the help of biomarkers from mass spectra.

PMID- 15841913
TI  - A contribution to sonograph image quality estimation using point spread function.
AB  - In medical sonography, sonograph image quality is an essential aspect for the
      safety of both patient and doctor. Its evaluation therefore requires an accurate
      and objective method for measurement. In this regard, a number of methods are in
      current use. Most of these are based on tissue mimicking phantom imaging. In
      contrast, we have used another principle based on Point Spread Function (PSF)
      analysis which is a product of the measuring system we have developed. In this
      case, the measured sonograph scans a small metallic ball target that moves in a
      water bath on a specified trajectory. The Region Of Interest (ROI) of the
      sonogram containing the ball target picture is digitised and the amplitude of the
      pixels analysed. The result is the PSF from which we calculate the lateral
      resolution (LR). For this purpose, we use our own original software. Using this
      method, we have to date been able to plot LR characteristics over the scanning
      plane. The method allows us to differentiate separate scanning lines and even
      multiple focal areas for dynamic focussing systems. It can detect malfunctions in
      dynamic focussing, size of aperture, time gain compensation function and/or
      transducer element failure. The procedure itself is not as easy or as fast to use
      as tissue mimicking phantoms or 3D signal to noise ratio evaluation, but it
      provides accurate and objective numeric parameters corresponding to the quality
      of image at any specified point over the whole scanning area. It is also a very
      powerful tool when used in combination with the other methods mentioned above.

PMID- 15841914
TI  - Non-linear mechanical behavior of visco-elastic biological structures-
      measurements and models.
AB  - Mechanical properties of biological structures affect functional ability of
      organism. Current knowledge is prevailingly concentrated on static
      characteristics. The present work analyzed dynamic mechanical responses of
      various biological materials. Following biological structures were measured:
      samples of aorta walls of human origin and from model organisms, human body
      surface, and samples of bones of various types and origin. Linear approximation
      leads in case of aortas and bones to simple Voight's model. Modules of elasticity
      (in tensile loading) of aortas were from 10(2) kPa to 10(3) kPa. Module of
      elasticity of bones were from 10(6) Pa to 10(10) Pa. Viscous coefficients of
      aortas were from 102 Pa.s to 10(3) Pa.s. Viscous coefficients of bones were from
      10(0) Pa.s to 10(2) Pa.s. Nonlinearities: We found that following types of
      nonlinearities are significant: strain-stress relationship, time-dependent
      changes in elastic as well as viscose bodies. Strain and stress is well
      approximated by quadratic function sigma = a epsilon2 + b epsilon + c with
      parameters a = 1833, b = 135, c = 20.0 (porcine aorta). Time-dependence in
      elastic coefficient: At the beginning of responses the elastic coefficient was of
      42% lower then at 0.02 s of duration of the response (porcine aortas). Analogical
      results follow also from experiments on other structures (skin, bones).

PMID- 15841915
TI  - Mechanical properties of selfexpandable stents.
AB  - The stents or stentgrafts (covered stents) are the medical instruments used in
      invasive radiology for miniinvasive treatment of stenosis and aneurisms
      especially in the blood circulation system. We measured and compared the
      mechanical parameters of different selfexpandable Nitinol stents, which differed
      in the geometry (radius and length), in the type of construction (number of
      branches and rising of winding) and in the diameter of the used wire. The results
      of measurements confirmed the theoretical assumptions that just the diameter of
      the Nitinol wire significantly influences the rigidity and the level of
      compressibility of the stent as well. The compromise must be found between the
      required rigidity of the stent and the minimal size of the delivery system. The
      exact description of the relation between the mechanical properties and geometry
      and construction of the stents enables us to design the stent to fit the
      patient's needs. The results of measurement are also necessary for the design and
      identification of the parameters of the models of the stents.

PMID- 15841916
TI  - Standardisation in ultrasonography: principle and diagnostic significance.
AB  - Disadvantage of ultrasonography is its dependence on subjective assessment of
      displayed images. The way how to minimize both intraobserver and interobserver
      differences is creation of standard conditions for examination including a
      quantitative approach to evaluation of tissue reflectivity. The oldest mode of
      standardisation is standardised A- scan, used in ophthalmology. It enables
      differentiation of echoes, reflected from different ocular structures and is
      helpful in assessment of extraocular muscle thickness. Standardisation of B-scan
      depends on the type of diagnostic device and is based on quantification of image
      echogenicity. In our study reference values of grey-level histogram were
      established for some thyroid diseases using standard setting of imaging
      parameters. Results indicate that both standardised A- and B-scan should be
      helpful in differential diagnostics.

PMID- 15841917
TI  - Spectral characteristics of the supramolecular complexes of polypyrrolic
      sensitizers and cyclodextrin carriers: usage in photodynamic therapy of tumors.
AB  - The objective of our work was to describe the photophysical properties
      (absorption and fluorescence) of the sensitizers TPPS4, ZnTPPS4 a PdTPPS4 and
      above all the complexes of these sensitizers with cyclodextrin carriers HP-alpha
      CD, HP-beta-CD and HP-gamma-CD (2-hydroxypropyl-alpha, beta, gamma-cyclodextrin)
      in a suitable environment for the cultivation of cancerous cell lines, and to
      determine the optimal radioactive conditions for maximizing photodynamic effects
      in cancerous cells.

PMID- 15841918
TI  - The cellular uptake of sensitizers bound to cyclodextrin carriers.
AB  - Photodynamic therapy of cancer uses the interaction of sensitizers and light to
      destroy cancer cells. In this study we tested the cellular uptake of meso
      tetrakis(4-sulfonatophenyl)porphine (TPPS4) and its complex PdTPPS4 in the
      presence or absence of 2-hydroxypropyl-cyclodextrins (hpCDs) on G361 human
      melanoma cells. Self-fluorescence in G361 cells were measured by Perkin-Elmer
      LS50B luminometer equipped with well plate reader accessory. Morphological
      changes in cells have been evaluated using inversion fluorescent microscope
      Olympus IX 70 and image analysis. The uptake of the sensitizer PdTPPS4 at the
      given time interval from 1 to 48 hours is markedly higher than the uptake of
      TPPS4. The highest uptake was found for sensitizer PdTPPS4 in combination with
      hpbetaCD. TPPS4 and PdTPPS4 especially in the supramolecular complex with
      nontoxic cyclodextrin carriers represent efficient sensitizers for photodynamic
      therapy in vitro on G361 cells.

PMID- 15841919
TI  - Age and sex variability of initial parts of the QRS complex displayed in
      isointegral maps of young people.
AB  - Although body surface electrocardiographic mapping is used also in clinical
      practice, there are only a few papers concerning the isointegral maps (IIMs) in
      children. We constructed IIMs of 169 healthy young people during the initial
      parts of the QRS complex: the first 20 ms (QRS20), 30 ms (QRS30), 40 ms (QRS40),
      and from 20 ms to 40 ms (QRS(20-40)). Subjects were divided into 6 groups: 9-10 y
      (F1, M1), 13-14 y (F2, M2), 18-19 y (F3; M3). We analysed the extreme values of
      each time integral. We found maxima and peak-to-peak values decreasing with age,
      while minima tended to increase (became less negative). Most age differences were
      found in IIM QRS(20-40) and between peak-to-peak values. Least differences were
      between minima. Maxima and peak-to-peak values were higher in males than in
      females. No significant differences were found in any extreme value between
      groups F1 and M1 except for IIM QRS20 maxima. Significant sex differences
      increased with age. The only significant difference found in minima was between
      F2 and M2. Most sex differences were found in IIM QRS20. We assume that our
      findings can be explained (at least in part) by the influence of heart-chest
      geometry.

PMID- 15841920
TI  - Influence of D-glucose on lipid solid support membrane system as attempt for
      biosensing of medically relevant molecules.
AB  - The influence of D-glucose on a lipid solid support system with the aid of
      impedance spectrocopy as a preliminary attempt for the biosensing of medical
      relevant molecules was studied. In spite of some shortcomings, s-BLM's proved to
      be an appropriate model for the study of lipid membrane-D-glucose interactions.
      The shortcomings were the roughness of the metal support, and the lack of
      homogeneity in the monolayer or multilayer lipid structures.

PMID- 15841921
TI  - Assessment of cellular damage by comet assay after photodynamic therapy in vitro.
AB  - The aim of this study was analysis of DNA damage in the cell line of the human
      melanoma G361 after photodynamic therapy (PDT) by comet assay. Photodynamic
      therapy is based on cytotoxic action of sensitizers (10 microM ZnTPPS4 fixed into
      1 mM cyclodextrin hpbetaCD) and light with a suitable wavelength. Single-cell gel
      electrophoresis (SCGE, comet assay) is a rapid and sensitive method for detecting
      DNA strand breaks at the level of single cells. Great amount of DNA damage was
      detected with the dose of irradiation of 0.1; 0.5 J and 2.5 J x cm(-2). Only
      radiation dose of visible light in the presence of sensitizers can induce DNA
      breaks of tumour cells. Cells with DNA damage appear as fluorescent comets with
      tails of DNA fragmentation. In contrast, cells with undamage DNA appear as round
      spots, because their intact DNA does not migrate out of the cell.

PMID- 15841922
TI  - Report on the course of study BZ-1003-BR following the changes in airways in
      stutterers with the help of pulse oscillometry (MasterScreen IOS).
AB  - Stuttering affects people all over the world. At the age of six years, about 1.5
      percent of children suffers from stuttering. Although stuttering resolves
      spontaneously upon reaching adulthood in approximately 80% of those affected, it
      continues to have significant health and social consequences. So far, its
      etiology remains unknown. The organic differences in those with stuttering and
      those free of speech problems have been evaluated. As a result of these
      examinations, it has been hypothesized that stuttering results from functional
      pneumoobstruction of the tracheobronchial tree in the peripheral respiratory
      passages. As for now, no similar therapeutic procedure, using a bronchodilating
      agent in the treatment of stuttering, has been described. Preliminary findings of
      a pilot study are surprisingly positive. In October of 2003, a multicenter open
      clinical trial (Stage III) to verify the effect of a sympathomimetic agent
      formoterol was initiated. The study is being realized in six centers in Moravia
      and enrolls approx. 40 patients (children, adolescents and young adults). First
      experience and initial evaluation of the cohort are presented here.

PMID- 15841923
TI  - Stability of bovine cytochrome C oxidase as studied after exposure to high
      hydrostatic pressure.
AB  - Structural and functional stability of bovine cytochrome c oxidase as a function
      of exposure to high hydrostatic pressure is reported. The pressure affects the
      stability of monomeric and dimeric enzyme quite differently. Exposure of the
      monomeric cytochrome c oxidase to pressures higher than 2.5 kbar causes
      dissociation of subunits III, VIa, VIb, VIIa with a 35-50% decrease in electron
      transport activity. Dimeric enzyme is more resistant to high hydrostatic pressure
      since subunits III and VIIa do not dissociate and the electron transport activity
      loss is minimal.

PMID- 15841924
TI  - Software for the analysis of species-specific vocalizations.
AB  - Vocalization calls are behaviorally relevant complex sounds that typically
      contain several harmonics and show frequency and amplitude modulation. In this
      paper, an introduction to a software tool for the analysis of species-specific
      vocalizations is presented. The algorithm automatically or under user supervision
      detects time-varying amplitude and frequency parameters, which can serve for the
      statistical analysis of calls or as the substrate for the manipulation and
      synthesis of artificial calls. The described program and its results will be used
      in studying the representation of complex sounds in the central nervous system.

PMID- 15841925
TI  - Examination of dentin surface using AFM (our experience).
AB  - Atomic force microscopy (AFM) as one the technique of Scanning Probe Microscopy
      is useful for imaging of surface structure. This method can yield three
      dimensional high-resolution topographic images of sample surfaces by using a
      scanning technique for conductors and insulators on atomic scale. It is based
      upon mapping of atomic-forces on a surface of an investigated sample. The method
      is useful not only in physics and chemistry; it can be also applied in biological
      fields. Special construction of AFM scanner enables to follow biological samples
      in liquid environments. Artifacts caused by dehydration of samples are removed
      this way. Dentin of human teeth is a vital hydrated tissue. It is strongly
      sensitive to dehydration and drying that are commonly used in preparation of
      samples in examinations by Scanning Electron Microscopy (SEM). We describe our
      experience in examination of dentin surfaces of extracted human third molars
      using contact method of AFM under moist conditions.

PMID- 15841926
TI  - Evaluating ventricular function with B-type natriuretic peptide in obstetric
      patients.
AB  - OBJECTIVE: To determine if a rapid serum assay for B-type natriuretic peptide
      (BNP) provides information regarding ventricular function in obstetric patients
      with acute dyspnea. STUDY DESIGN: A review of 17 charts for 15 patients was
      undertaken. Seven patients had preeclampsia, 3 had preterm labor treated with
      aggressive tocolysis, and 5 had underlying cardiac and/or pulmonary disease. Each
      presented with signs and symptoms consistent with acute dyspnea. Serum BNP levels
      were obtained and other standard diagnostic procedures performed. Each patient
      was treated based on the findings of the standard diagnostic procedures. RESULTS:
      For the 7 patients with preeclampsia, elevated serum BNP levels correlated with
      acute ventricular overload that responded to volume management and diuresis. Two
      patients had marked elevation of serum BNP levels and were found to have
      significant left ventricular dysfunction that was not apparent by standard
      clinical evaluation. For preterm labor patients on tocolysis and patients with
      underlying cardiac or pulmonary disease, serum BNP levels were elevated for 5 of
      6 patients with evidence of acute volume overload. CONCLUSION: Serum BNP levels
      provided useful information for the clinical evaluation and management of
      obstetric patients with acute dyspnea. In 2 patients, more serious cardiac
      dysfunction was detected with BNP than with clinical evaluation alone.

PMID- 15841927
TI  - Menopausal vasomotor symptoms: a review of causes, effects and evidence-based
      treatment options.
AB  - Vasomotor symptoms are the most common medical complaint of perimenopausal and
      postmenopausal women. Frequent vasomotor symptoms can be disabling, affecting a
      woman's social life, psychological health, sense of well-being and ability to
      work. Women with hot flushes are more likely to experience disturbed sleep,
      depressive symptoms and significant reductions in quality of life as compared to
      asymptomatic women. Despite the prevalence and impact of these symptoms, the
      pathophysiology of hot flushes is unclear; however, estrogen withdrawal clearly
      plays an important role. It is postulated that declining estrogen concentrations
      may lead to changes in brain neurotransmitters and instability in the
      hypothalamic thermoregulatory center. The most effective therapy for relieving
      vasomotor symptoms and reducing their impact on quality of life is hormone
      therapy. Other options for women who decline hormone therapy include selective
      serotonin reuptake inhibitors and related agents. Most herbal therapies that have
      been evaluated in placebo-controlled trials have shown no clinically significant
      benefit.

PMID- 15841928
TI  - Prevalence of hysterectomy and associated factors in women Veterans Affairs
      patients.
AB  - OBJECTIVE: To estimate the prevalence of hysterectomy and associated factors in
      women veterans who access care at a Veterans Affairs medical center. STUDY
      DESIGN: A survey that included questions regarding hysterectomy status,
      demographics, medical history and validated mental health measures was mailed to
      1,935 women who received care at the VA Puget Sound Health Care System between
      October 1996 and January 1998. RESULTS: The overall prevalence of hysterectomy
      was 32%, with 12% of 18-39-year-olds, 35% of 40-49-year-olds, and 57% of women 50
      years old or older reporting having had a hysterectomy. In multivariable
      analyses, older age (OR 1.1, 95% CI 1.07-1.09), multiparity (OR 1.6, 1.14-2.2),
      self-reported polycystic ovary syndrome (OR 3.3, 1.81-5.9), chronic pelvic pain
      (OR 3.2, 2.1-4.9), irritable bowel syndrome (OR 1.8, 1.3-3.1) and premenstrual
      syndrome (OR 1.6, 1.1-2.3) were associated with prior hysterectomy. When factors
      associated with posttraumatic stress disorder in this population were omitted
      from the model, age (OR 1.07, 1.05-1.08), multiparity (OR 1.4, 1.0-1.9), a family
      history of ovarian cancer (OR 1.8, 1.2-2.8) and posttraumatic stress disorder (OR
      1.4, 1.02-1.87) were associated with prior hysterectomy. CONCLUSION: The
      prevalence of hysterectomy may be higher among women veterans as compared with
      published rates for the general population and may be related to chronic pain
      syndromes and/or posttraumatic stress disorder.

PMID- 15841929
TI  - Randomized comparison of 3 misoprostol protocols for abortion induction at 13-20
      weeks of gestation.
AB  - OBJECTIVE: To evaluate the induction-to-abortion time of 3 pharmacokinetic-based
      protocols at 13-20 weeks of gestation. STUDY DESIGN: A randomized trial was
      conducted on 153 patients. The oral group (n = 51) received 100 microg
      misoprostol orally every 2 hours, the vaginal group (n = 51) received 200 microg
      misoprostol vaginally every 4 hours, and the sublingual group (n = 51) received
      100 microg misoprostol sublingually every 2 hours. RESULTS: The mean induction-to
      delivery time was shorter in the sublingual group (mean, 651 +/- 507) as compared
      to the vaginal group (mean, 1,056 +/- 634, p = 0.01). The number of patients who
      delivered within 12 hours was significantly higher in the sublingual group (n =
      39, 78%) as compared to the oral (n = 26, 52%) and vaginal (n = 20, 40%) groups
      (p < 0.001). The numbers of patients who delivered within 24 hours were
      comparable in the sublingual (n = 47, 94%) and oral (n = 46, 92%) groups but
      higher than in the vaginal group (n = 39, 78%; p = 0.02). The total misoprostol
      dose was 543 +/- 422 microg in the sublingual group, 878 +/- 533 microg in the
      vaginal group and 741 +/- 413 microg in the oral group (p < 0.001). CONCLUSION: A
      pharmacokinetic-based application of 100 microg of sublingual misoprostol every 4
      hours is more effective for induction of second-trimester abortion as compared to
      100 microg oral misoprostol every 2 hours and 200 microg vaginal misoprostol
      every 4 hours.

PMID- 15841930
TI  - Exercise during pregnancy: a critical appraisal of the literature.
AB  - To review the effects of exercise during pregnancy on fetal and maternal
      outcomes, a selective literature search was performed using MEDLINE, the Cochrane
      Database and bibliographies from relevant articles to identify additional
      references. The data on exercise during pregnancy are limited but suggest that
      moderate exercise during a low-risk pregnancy does not lead to adverse outcomes
      for the fetus or mother and improves overall maternal fitness and well-being. The
      data examining the impact of exercise on labor outcomes, maternal weight gain and
      fetal weight are conflicting. Moderate exercise in the low-risk pregnancy
      improves maternal well-being and does not seem to have adverse effects on the
      fetal or maternal outcome. However, further studies are needed.

PMID- 15841931
TI  - Analysis of the success rates of Burch colposuspension in relation to Valsalva
      leak-point pressure.
AB  - OBJECTIVE: To compare the success rates of Burch colposuspension in relation to a
      Valsalva leak-point pressure (VLPP) cutoff level of 60 cm H2O and to examine
      other predictive factors for intrinsic sphincter deficiency, such as maximal
      urethral closure pressure (MUCP) and functional urethral length (FUL), in an
      attempt to define the urodynamic contraindications to Burch colposuspension.
      STUDY DESIGN: From March 1999 to February 2001, among patients who had undergone
      Burch colposuspension after being diagnosed as having stress urinary incontinence
      at the Yonsei University Medical Center Urogynecology Clinic, 79 patients
      eligible for continuous postoperative follow-up were enrolled in the study.
      Patients with past histories of hysterectomy and/or incontinence surgery were
      excluded from the study, and all patients included in the study had pelvic organ
      prolapse stage II or less. Urodynamic studies were performed as a preoperative
      evaluation, and recurrence of stress urinary incontinence after surgery was
      diagnosed through thorough history and meticulous urodynamic evaluations.
      RESULTS: The mean age was 57.66 +/- 9.99 years, mean parity was 3.71 +/- 4.38,
      menopausal rate and mean age at menopause were 81.0% (64 of 79) and 50.31 +/-
      4.60 years, respectively, and the proportion of patients receiving hormone
      replacement therapy was 10.1% (8 of 79). The success rates in 2 groups, VLPP > or
      = 60 cm H2O (n=55) and < 60 cm H2O (n=24) were 94.55% and 91.67%, respectively,
      demonstrating no statistical significance (p > 0.05). The MUCP and FUL values
      were within normal ranges in both groups (MUCP, 66.98 +/- 24.04 versus 66.23 +/-
      22.89 cm H2O, p>0.05; and FUL, 36.33 +/- 7.31 versus 38.71 +/- 8.54 mm, p >
      0.05), without a significant difference. The Pearson correlation coefficients for
      VLPP versus MUCP and VLPP versus FUL were 0.50 (p < 0.001) and 0.57 (p < 0.001),
      respectively, demonstrating a significant positive correlation. CONCLUSION: A
      VLPP level < 60 cm H2O does not represent an absolute contraindication to Burch
      colposuspension, provided that other parameters, such as MUCP and FUL, are within
      acceptable ranges. To select appropriate candidates for Burch colposuspension, a
      comprehensive evaluation of urodynamic parameters is mandatory.

PMID- 15841932
TI  - Seasonality and immediate antecedents of sexual intercourse in adolescents.
AB  - OBJECTIVE: To assess immediate antecedents of and seasonal variations in sexual
      intercourse among a focused population of medically indigent adolescent females
      in Houston, Texas. STUDY DESIGN: From June 2001 to March 2002 we solicited a
      convenience sample of adolescent females during their visit to a school-based
      clinic. The survey consisted of 34 multiple choice questions targeting immediate
      antecedents of sexual behavior. Demographic characteristics and survey responses
      were compared with t tests and ANOVA. The chi2 goodness of fit test and test of
      homogeneity were used to assess seasonality. RESULTS: One hundred thirty-three
      teenagers completed our survey. Both African American and Hispanic teens were
      significantly more likely to report that their sexual debut occurred in June (p <
      0.01 and = 0.02, respectively). More than 50% of those surveyed reported having
      sex either in their homes or in the homes of their partners. Doing "nothing" was
      the most common antecedent activity for sexual intercourse. There were no
      statistically significant differences in location or antecedent activity for
      first or most recent sexual intercourse between teens with and without prior
      pregnancy. CONCLUSION: Both the timing and location of sexual intercourse among
      the teens in this study suggest that unsupervised time may be a factor
      contributing to sexual activity in teens.

PMID- 15841933
TI  - Does the diameter of an endometrioma predict the extent of pelvic adhesions
      associated with endometriosis?
AB  - OBJECTIVE: To correlate ovarian endometrioma diameter with the extent of pelvic
      adhesions. STUDY DESIGN: Forty women with unilateral ovarian cysts thought to be
      endometriomas were prospectively recruited. The interventions were transvaginal
      ultrasound to measure the size of the ovarian endometrioma and a laparoscopic
      surgical procedure, including detailed pelvic assessment. Main outcome measures
      were pelvic adhesion scores using the American Fertility Society revised
      classification of endometriosis. RESULTS: Thirty-two women met the inclusion
      criteria. Twelve had an endometrioma < 3 cm in diameter; 12, 3-5 cm; and 8, > 5
      cm. Adhesion scores from various anatomic areas did not differ across these 3
      groups. No correlation between the size of the endometrioma and associated pelvic
      adhesions was found using multiple regression analysis. CONCLUSION: The size of
      an endometrioma measured by transvaginal ultrasound does not correlate with the
      extent of adhesive disease. Small (< 3 cm) endometriomas may be associated with a
      considerable degree of pelvic adhesions.

PMID- 15841934
TI  - Computed tomographic features of tuboovarian abscess.
AB  - OBJECTIVE: To describe the spectrum and frequency of computed tomographic (CT)
      features in tuboovarian abscess (TOA) in order to increase the utility of
      computed tomography in diagnosing this condition. STUDY DESIGN: Search of our
      hospital registry found 22 patients diagnosed with TOA who underwent pelvic
      tomography between the years 1998 and 2001. A retrospective review of their CT
      scans was performed, and the CT features of TOA were recorded. Clinical signs and
      symptoms were also summarized. RESULTS: All 22 patients presented with lower
      abdominal pain. Additional clinical signs of TOA, such as a palpable abdominal
      mass (23%), vaginal discharge (27%) and fever (36%), were less common. On
      tomography the majority of TOAs were unilateral (73%) and multilocular (89%) and
      had fluid density (95%) and a thick, uniform, enhancing wall (95%). Other common
      CT findings were thickening of the mesosalpinx (91%) and infiltration into pelvic
      fat (91%). Less common CT findings included bowel thickening (59%), thickening of
      the uterosacral ligaments (64%) and pyosalpinx (50%). Ascites, lymphadenopathy,
      peritoneal involvement and hydronephrosis were uncommon findings on tomography.
      CONCLUSION: Computed tomography is a useful imaging modality in the diagnosis of
      TOA, especially in cases that are clinically indeterminate. Recognition of the
      spectrum of CT findings and their frequency can result in improved CT diagnosis
      of this disease.

PMID- 15841935
TI  - Metastatic uterine serous carcinoma originating in an endometrial polyp: a report
      of 2 cases.
AB  - BACKGROUND: Endometrial carcinoma is the most common cancer of the female genital
      tract. Two histologic variants have been described: an estrogen-dependent form
      and a more aggressive, non-estrogen-dependent form, which includes uterine serous
      carcinoma. CASES: Two cases of uterine serous carcinoma were confined to an
      endometrial polyp without myometrial invasion and were widely metastatic. One
      patient presented with abdominal pain and constipation, while the other patient
      was asymptomatic. Both patients had elevated CA-125 levels. At the time of
      surgery, these patients were found to have extensive carcinomatosis and underwent
      surgical staging procedures that required bowel resections. Pathology showed
      metastatic disease originating in a small focus of serous adenocarcinoma at the
      tip of an endometrial polyp. Combination chemotherapy was planned; but 1 of the
      patients died prior to its initiation. CONCLUSION: These cases emphasize the
      aggressive nature of uterine serous carcinoma despite insignificant myometrial
      invasion.

PMID- 15841936
TI  - Twin pregnancy in the horns of a bicornuate uterus after in vitro fertilization
      and split embryo transfer: a case report.
AB  - BACKGROUND: Twin pregnancies located in the separate horns of a bicornuate uterus
      following in vitro fertilization and embryo transfer have been rarely reported.
      CASE: A 32-year-old woman presented with primary infertility and was diagnosed as
      having a bicornuate uterus. Because of severe male factor infertility, in vitro
      fertilization and embryo transfer were recommended. Embryo transfer resulted in a
      twin pregnancy with a fetus in each horn. CONCLUSION: Embryo transfer into
      separate uterine cavities resulted in a twin pregnancy, with a fetus in each
      horn, and term delivery. Split embryo transfer into each uterine cavity of an
      uncorrected bicornuate uterus is a feasible treatment option in selected
      patients, provided that the couple is counseled about the risks involved.

PMID- 15841937
TI  - Postmenopausal bleeding secondary to a Dalkon Shield retained for 33 years: a
      case report.
AB  - BACKGROUND: Although the Dalkon Shield intrauterine device (IUD) was removed from
      the market in the early 1970s, some women currently in their late 50s and early
      60s may still have the Shield in their uteri. An IUD retained for a long time is
      very rare but can be a cause of postmenopausal bleeding. CASE: A 58-year-old,
      postmenopausal woman presented with vaginal bleeding and spotting of 8 months'
      duration. Careful investigation of her history revealed that she had undergone
      IUD placement 33 years earlier. She was not sure about the type and whether the
      IUD was removed or expelled subsequently. There was no string visualized in the
      vagina. An office endometrial biopsy revealed Actinomyces and an associated
      polymorphonuclear cell exudate. A retained Dalkon Shield was diagnosed and
      removed hysteroscopically. CONCLUSION: Providers should include "retained IUD" in
      the differential diagnosis of postmenopausal bleeding. In addition to endometrial
      biopsy, hysteroscopic evaluation of the uterine cavity is a valuable tool in the
      diagnosis and treatment of such bleeding. A retained IUD may cause postmenopausal
      bleeding secondary to chronic endometritis or migration into the uterine wall.
      Hysteroscopic dislodgement and removal may be challenging due to chronic
      embedding within the uterine wall.

PMID- 15841938
TI  - Antenatal sonographic diagnosis of massive subchorionic hematoma: a case report.
AB  - BACKGROUND: Massive subchorionic hematoma (MSH), described by Breus in 1892
      (Breus mole), is a rare but serious condition in pregnancy in which a large
      amount of blood, mainly maternal, collects and dissects the chorionic plate from
      the villous chorion. CASE: A case of MSH was complicated by intrauterine growth
      retardation (IUGR) and intrauterine fetal death at 23 weeks' gestation. Pregnancy
      was complicated by advanced maternal age and chronic hypertension. There was no
      antenatal vaginal bleeding. Ultrasound at 19 weeks showed a small-for-gestational
      age fetus, echogenic bowel and globular placenta. Amniocentesis revealed a normal
      male karyotype. At 23 weeks the patient presented with vaginal spotting, cramping
      and absent fetal heart tones. Labor was induced with misoprostol, and vaginal
      delivery occurred. The placenta showed an organized thrombus adherent to the
      chorionic plate, and a large subchorionic hematoma comprised at least half the
      disc volume. CONCLUSION: Antenatal sonographic diagnosis of MSH and IUGR can be
      achieved.

PMID- 15841939
TI  - Bilateral tubal pregnancy after natural conception: a case report.
AB  - BACKGROUND: Bilateral tubal pregnancy is very rare and usually follows ovulation
      stimulation. CASE: A 36-year-old woman with acute pelvic pain underwent emergency
      laparoscopy for suspected left ruptured tubal pregnancy. Bilateral hematosalpinx
      with a ruptured left tubal pregnancy and active bleeding from the right fallopian
      tube was noted during surgery, and bilateral salpingectomy was performed by
      laparoscopy. Pathologic examination of the left tube confirmed the presence of
      conception products and trophoblastic tissue. The right salpingectomy specimen
      contained some trophoblastic tissue resembling an earlier tubal pregnancy encased
      in a cyst. CONCLUSION: This was a rare case of spontaneous bilateral tubal
      pregnancy after conception at different times. The explanation of the
      presentation is uncertain. Laparoscopy remains the cornerstone of diagnosis and
      treatment in the majority of women with a tubal pregnancy; this is especially
      true in complex cases, such as bilateral tubal pregnancy.

PMID- 15841940
TI  - Anaphylactoid syndrome of pregnancy after intracervical dinoprostone for cervical
      ripening: a report of 3 cases.
AB  - BACKGROUND: Three cases of anaphylactoid syndrome of pregnancy developed in
      association with the use of intracervical dinoprostone for cervical ripening.
      CASES: All cases occurred at our institution between October 1996 and February
      2001. The patients developed respiratory symptoms shortly after placement of 0.25
      mg of intracervical dinoprostone gel. Hemodynamic changes, manifested by tetanic
      uterine contractions and fetal heart rate decelerations, followed. Subsequently
      all 3 patients developed disseminated intravascular coagulation, characterized by
      severe hypofibrinogenemia. CONCLUSION: There appears to be an association between
      intracervical dinoprostone for cervical ripening and anaphylactoid syndrome of
      pregnancy. Clinicians utilizing this route of dinoprostone administration should
      be familiar with this rare but potentially life-threatening complication.

PMID- 15841941
TI  - [Osteoporosis: crisis state].

PMID- 15841942
TI  - [Epidemiology and risk factors for osteoporosis].
AB  - It has been estimated that 40 % of white women aged 50 years will suffer at least
      one of the major osteoporotic fractures (hip, vertebrae, wrist) before the end of
      their life. Bone mineral density (BMD) measurement is the basis of osteoporosis
      diagnosis and is generally considered as a key element to identify high risk
      subjects who should benefit most from a bone active treatment preventive of
      fractures. However, for a given BMD level, the risk of fracture varies with age
      and with the presence of other risk factors (personal or familial history of
      fracture, low weight, corticotherapy, fall-related risk factors etc.). In the
      future, it is probable that densitometry results will be expressed in terms of
      risk of fracture within the next 10 years. Different intervention thresholds
      could then be defined depending on the age of the subject, the level and nature
      of the risk factors, as well as the type of preventive or therapeutic actions
      considered. In the elderly, fall-related factors such as neuromuscular and visual
      disorders have a weight similar to the one of BMD in the determinism of hip
      fracture. Recently, several randomized controlled trials have shown that
      multifactorial preventive programs tailored to individual risk factors or
      exercise programs emphasizing balance training can reduce the risk of falls in
      the elderly by 25 to 30%. The efficacy of such measures on fracture prevention
      must be demonstrated.

PMID- 15841943
TI  - [Genetics of osteoporosis].
AB  - Osteoporosis is a multifactorial disease involving genetic component and several
      environmental factors. Some rare diseases that are associated with osteoporosis
      such as Lobstein disease or the "pseudoglial osteoporosis" syndrom are
      monogenetic. Nevertheless common osteoporosis is a polygenic affection resulting
      from the interaction between the polymorphism of different genes and the
      environmental factors. The genetic component of osteoporosis encompasses roughly
      60 to 70% of bone mineral density, whereas the effect on fracture risk seems
      lower because of the importance of other environmental factors as falls. Many
      polymorphisms of candidate genes involved in the regulation of bone mass have
      been correlated to bone density. It is likely that many genes participate to the
      regulation of bone density although the existence of a major gene is highly
      suspected. Moreover linkage analysis after genome-wide search in populations with
      severe osteoporosis has focused on some regions of interest (QTL) on the
      chromosomes. This will allow to localize one or more specific genes. The current
      genetic studies on different populations affected by osteoporosis or not will be
      useful in order to better predict the fracture risk in association with bone
      density and biochemical markers of bone turnover. Moreover, this will lead to the
      development of new treatments of osfeoporosis and will help to adapt the therapy
      for individual patients.

PMID- 15841944
TI  - [Physiopathology of osteoporosis].
AB  - PURPOSE: The pathophysiology of osteoporosis has seen many recent progress
      especially with the use of genetically modified animal models. CURRENT KNOWLEDGE
      AND KEY POINTS: Among many discoveries, one can notice the crucial role of LRP5,
      GH, IGF-1 and the sex hormones receptors in the acquisition of the peak bone
      mass, the control of bone remodeling by the sympathetic nervous system and his
      implication as a transmitter of mechanical loading in bone. Also, the role of
      estrogen and androgen receptors as well as the aromatase is specified according
      to sexes. The role of growth plate's chondrocytes in the installation of the
      trabecular bone network is better and better demonstrated. The greater periosteal
      apposition in men, mediated by androgens receptor, seems to explain the greatest
      radial growth and so the greatest bone resistance to mechanical strains like a
      lower fracture rate in men compared to women. The bone microarchitecture and
      quality explain an important part of the mechanical properties of bones and why
      considering the same bone mass one bone is breaking and another one not. FUTURE
      PROSPECTS AND PROJECTS: Many therapeutic applications should finalize the
      discovery of these new bone cells signalisation pathways.

PMID- 15841945
TI  - [Postmenopausal osteoporosis diagnostic methods and their indications].
AB  - The value of bone density in predicting fracture is established, and there is a
      general consensus that bone mineral density (BMD) measurement should be
      considered in patients with conditions that place them at high risk for
      osteoporotic fracture. However, low bone density alone is judged to be
      insufficient to warrant treatment. Clinical risk factors have an important role
      in determining who should have BMD measurement, in assessing risk of fracture,
      and in determining who should be treated. A history and physical examination is
      essential in evaluating fracture risk and should include change in posture and
      risk of fall. It has been suggested that the diagnosis and treatment of
      osteoporosis should depend on risk-bases assessment rather than only on the
      assessment of a T-score. From analysis of guidelines, the French Agency of Health
      Accreditation and Evaluation recommends BMD measurement in the following
      indications: radiological evidence of vertebral fracture; previous fragility
      fracture; previous causes of secondary osteoporosis; maternal history of hip or
      vertebral fracture; premature menopause (< 40 years); body mass index < 19 kg/m2;
      glucocorticoid therapy (> 7.5 mg/day oral prednisolone or equivalent for 3 months
      or more).

PMID- 15841946
TI  - [Secondary osteoporosis and internal medicine].
AB  - INTRODUCTION: The term 'primary' osteoporosis refers to osteoporosis that results
      from the involutional losses associated with aging and, in women, additional
      losses related to natural menopause. Osteoporosis that is caused or exacerbated
      by other disorders or medication exposures is referred to as 'secondary'
      osteoporosis. CURRENT KNOWLEDGE AND KEY POINTS: This article describes the major
      causes and provides a framework for the diagnostic investigation of patients with
      suspected of having secondary osteoporosis. There are numerous causes of
      secondary bone loss, including endocrine disorders, disorders of the
      gastrointestinal or biliary tract, rheumatic diseases, haematological diseases,
      immobilization, adverse effects of drug therapy, and a wide miscellaneous group.
      FUTURE PERSPECTIVES: Secondary osteoporosis is potentially reversible during the
      treatment of the underlying disease. It must be identified and induce a
      symptomatic treatment in all cases plus an etiologic treatment when possible.

PMID- 15841947
TI  - [Osteoporosis in men: epidemiology, physiopathology, diagnosis, prevention and
      treatment].
AB  - PURPOSE: This article reviews the most current information about epidemiology,
      risk factors, diagnosis, prevention and management of male osteoporosis. MAIN
      POINTS: Although osteoporosis is often regarded as a disease of women, 30% of
      osteoporotic fractures occur in men. Risk factors for osteoporosis or fractures
      in men include previous fragility fractures, maternal history of fragility
      fracture, hypogonadism, low body mass index, smoking, high alcohol consumption,
      low calcium intake, corticoid therapy, physical inactivity, and the presence of
      conditions such as hyperthyroidism, hyperparathyroidism, hypercalciuria or
      chronic inflammatory diseases. Treatment of osteoporosis is recommended in men
      aged > 65 years with low bone mass (T-score < -2.5), in men aged 50 to 65 years
      with low bone mass and at least one risk factor for osteoporosis or fracture, in
      men aged < 50 years with Z-score < -2 with at least one risk factor for
      osteoporosis or fracture and in men with at least two fragility fractures. FUTURE
      ASPECTS: Further studies are needed to better estimate the benefit of of
      bisphophonates in the prevention of glucocorticoid-induced osteoporosis and the
      prevention of androgen-deprivation therapy (treatment of prostate cancer) in men
      at high-risk for osteoporosis, of parathyroid hormone (1-34) in male primary
      osteoporosis, and of androgen therapy in men with symptoms (including low bone
      mineral density) and biological signs (with low blood free testosterone levels)
      of hypogonadism.

PMID- 15841948
TI  - [Hyperparathyroidism and osteoporosis].
AB  - INTRODUCTION: In patients with primary hyperparathyroidism, a definite diagnosis
      is the first step in the management strategy and relies on appropriately selected
      and carefully interpreted laboratory tests. Parathyroid hormone assays are being
      increasingly performed as part of the routine evaluation of osteoporosis. CURRENT
      KNOWLEDGE AND KEY POINTS: In this setting, laboratory tests are often consistent
      with primary hyperparathyroidism but should be interpreted with caution. FUTURE
      PERSPECTIVES: Bone mineral density measurements are useful for assessing the
      impact of primary hyperparathyroidism. The recommended bone mineral density
      cutoffs for selecting patients requiring parathyroidectomy were lowered in 2003,
      and the number of surgically treated patients has increased as a result.
      Parathyroidectomy remains the treatment of choice given the low mortality
      associated with this procedure and the absence of pharmacological alternatives
      suitable for long-term use.

PMID- 15841949
TI  - [Postmenopausal osteoporosis: current treatment].
AB  - Treatments for post menopausal osteoporosis can reduce by 50 % the risk of
      fracture, in patients having low bone mineral density, with ou without prevalent
      fractures. The treatment of calcium and vitamin D insufficiencies is necessary in
      parallel. Based on anti fracture efficacy of treatments, it is relevant to assess
      post menopausal women for the risk of osteoporotic fractures, based on clinical
      risk factors and bone mineral density measurements.

PMID- 15841950
TI  - [New treatments in osteoporosis].
AB  - New intermittent regimens with bisphosphonates such as oral ibandronate, and
      maybe annual intra-venous zoledronate, will be useful additions to the treatment
      of post-menopausal osteoporosis. Strontium ranelate is a new molecule that both
      inhibits bone resorption and stimulates bone formation, with proven efficacy to
      reduce fracture incidence. Teriparatide (1-34 fragment of parathyroid hormone),
      using daily subcutaneous injections, has also proven its efficacy to decrease
      vertebral and peripheral fracture risk in postmenopausal osteoporotic women. In
      the next five years, new SERMs and inhibitors of RANK-ligand might be new
      treatment options.

PMID- 15841951
TI  - [Current role of hormone replacement therapy in the prevention of postmenopausal
      osteoporosis: gynecologic point of view].
AB  - Hormonal Replacement Therapy (HRT) of the menopause has already proved to be
      effective in preventing bone loss and reducing the risk of fractures in
      postmenopausal women. Up until 2002, HRT was widely proposed and prescribed by
      French practitioners, in particular with regard to the prevention of
      osteoporosis. The results of two major studies, one American, the Women's Health
      Initiative (WHI) Study, and the other British, the Million Women Study (MWS),
      published in July 2002 and August 2003, have called into question the hitherto
      favourable benefits/risks ratio of HRT after finding an increased incidence of
      breast cancer and heart disease amongst women undergoing this treatment.
      Following these studies, the European and French health authorities have issued
      new recommendations regulating and restricting the use of HRT with a drastic
      restriction on the indications for its use in the prevention of osteoporosis.
      These new recommendations are the subject of controversy and pose new problems
      for practitioners.

PMID- 15841952
TI  - The American Board of Clinical Neuropsychology and American Academy of Clinical
      Neuropsychology: milestones past and present.

PMID- 15841953
TI  - Board certification in clinical neuropsychology: a response to Rohling et al.
AB  - Board certification is intended to protect the public by identifying
      practitioners that have met minimum standards for education and training in their
      specialty or discipline. For varied reasons, clinical neuropsychology, like
      professional psychology as a whole, has struggled to achieve levels of board
      certification comparable to the medical profession. Rohling, Lees-Haley,
      Langhinrichsen-Rohling, & Williamson (2003) have recently published a critique of
      the board certification process in clinical neuropsychology as it is conducted by
      American Board of Clinical Neuropsychology (ABCN), arguing that one reason for
      this failure is the overly restrictive nature of the process. In their paper,
      Rohling et al. provide a signal detection analysis that makes several assumptions
      about the process and conclude with recommendations for improving the process to
      better identify "competent" neuropsychologists in practice. While we agree in
      principle with many of their recommendations, and ABCN had, in fact, implemented
      several prior to publication of their article, the article contains many faulty
      assumptions and logical inconsistencies that we believe are harmful to
      constructive review of the certification process. In this article, we provide a
      critical review of their analysis and present new and additional data that
      demonstrate the procedure is not overly restrictive. A primary consideration is
      the low incidence of seeking board certification among professionals who identify
      themselves as neuropsychologists (i.e., a low application rate), rather than an
      overly restrictive process. We describe steps taken to improve the process and
      conclude that there are numerous areas of agreement with Rohling et al.,
      including the need for ongoing review and continued improvement in the board
      certification process in all psychological specialties.

PMID- 15841954
TI  - Clinical rating of cortical atrophy and cognitive correlates following traumatic
      brain injury.
AB  - We report on the utility of using a rapid, easy-to-use, visually based semi
      quantitative neuroimaging atrophy rating scale in individuals with traumatic
      brain injury (TBI) and normal control subjects. Magnetic resonance (MR) scans
      were rated using a standardized semi-quantitative MR rating method. A four-point
      scale was used to rate each scan for atrophy in frontal, temporal, and parietal
      areas. Seventy-five TBI subjects (50 males, 25 females) and 75 age- and gender
      matched control subjects were compared for atrophy ratings. Clinical atrophy
      ratings were also compared to a quantitative measure of atrophy, the ventricle-to
      brain ratio, and with the TBI subjects' scores on standard neuropsychological
      tests. TBI patients had significantly higher clinical atrophy ratings in frontal
      and temporal lobe areas compared to controls. The clinical atrophy ratings
      significantly correlated with the ventricle-to-brain ratio, a quantitative
      measure of atrophy in the same TBI subjects. Higher clinical ratings of frontal
      and temporal atrophy correlated with deficits in memory and executive function.
      These findings indicate that clinical ratings of trauma-induced atrophy can be
      reliably performed and are associated with neuropsychological outcome and
      quantitative measures of cerebral atrophy.

PMID- 15841955
TI  - Validity of the WCST-64 after traumatic brain injury in children.
AB  - The Wisconsin Card Sorting Test-64 (WCST-64) is a recently normed modification of
      the Wisconsin Card Sorting Test (WCST) that utilizes only one deck of cards. The
      present study investigated the validity of the WCST-64 in a sample of fifty-six
      10- to 16-year-old children with traumatic brain injury (TBI). Standard scores
      for perseverative responses from the WCST-64 and from the full-length WCST shared
      83% of common variance. Less than 10% of this sample had a discrepancy between
      the respective indexes that was greater than one standard deviation. Correlations
      with external criteria such as length of coma and Full Scale IQ were not
      significantly different between the two versions of the instrument. The findings
      suggest that the WCST-64 may be used interchangeably with the original WCST in
      older children with TBI.

PMID- 15841956
TI  - The status of empirical support for treatments of attention deficits.
AB  - Deficits in attention and self-regulation are common complaints associated with a
      number of disorders across the lifespan. The need to address attentional deficits
      is based on the premise that attention is a precursor and prerequisite to
      information processing and related cognitive tasks as well as a key factor in the
      success of other rehabilitation efforts. Many treatment programs have been
      developed with the intention of restoring or rehabilitating the impaired
      components of attention; the number and variety of attention programs is
      increasing rapidly. The purpose of this article is to evaluate available
      empirical support regarding the efficacy of treatments for remediation of
      attention deficits across disorders and age levels. The search of the major
      databases yielded 83 studies that included treatment of attentional deficits.
      Empirical studies were reviewed and categorized by the type of trial, whether or
      not the study included a control group, and the nature of the control group. The
      methodology and results of each study were then rated. For each treatment
      identified, the aggregated studies were then considered by the disorder of the
      samples included in the studies. Results indicated that, regardless of the
      treatment program or population, the existing research does not provide
      sufficient evidence to reach any conclusions about the efficacy of programs
      designed to address attention deficits. Before any conclusions, positive or
      negative, can be drawn, there is a need for more rigorous study of available
      treatment programs across age levels and disorders, with sufficient baseline and
      outcome data as well as control or alternative treatment conditions.

PMID- 15841957
TI  - Similarities and differences in Wechsler Intelligence Scale for Children--Third
      Edition (WISC-III) profiles: support for subtest analysis in clinical referrals.
AB  - Our study supports the reliability and validity of profile analysis in children
      with neurobiological disorders. Three mutually exclusive WISC-III profiles were
      identified that characterized the majority of children with autism (low coding or
      Freedom from Distractibility Index with low Comprehension), attention deficit
      hyperactivity disorder and learning disability (low Coding or FDI without low
      comprehension), and brain injury (low Performance without low Coding or FDI). The
      profiles suggest attention, writing, and performance speed deficits in autism,
      ADHD, and LD; global visual-motor problems in brain injury; and specific
      difficulty with language comprehension and social reasoning in autism. Children
      with anxiety, depression, and behavior disorders did not exhibit distinct
      profiles. Our profile analysis is based on the simple rank ordering of standard
      scores. The profiles are clinically useful because they may alert clinicians to
      certain diagnostic possibilities, they reveal characteristic strengths and
      weaknesses that have implications for educational intervention, and they are
      consistent with preliminary WISC-IV data.

PMID- 15841958
TI  - The Fake Bad Scale and MMPI-2 F-family in detection of implausible psychological
      trauma claims.
AB  - We tested the validity of the Lees-Haley Fake Bad Scale (FBS) and the family of
      MMPI-2 F scales (F-family; F, F(p), and F-K scales) in predicting improbable
      psychological trauma claims in an applied setting. Litigants reporting
      implausible symptoms long after minor scares and nonlitigants clinically referred
      following severe stressors completed the MMPI-2. Both groups were naturally
      matched on social class. The FBS demonstrated sensitivity, specificity, and
      positive predictive power in the detection of atypical problems but the F-family
      showed poor utility. FBS cutting scores derived from logistic regression were
      applied to a third group made up of litigants with histories of undeniably severe
      traumas. A substantial number of this third group scored above cutoffs for
      exaggeration, but this finding is ambiguous. Reasons for the F-family's
      insensitivity to real-world exaggeration may include using student simulators for
      validation and content reflective of psychotic simulation. The superiority of the
      FBS in applied forensic settings could derive from its development in actual
      litigants and content reflective of nonpsychotic exaggerations. The FBS appears
      acceptable for use in applied forensic settings where persons seek compensation
      for nonpsychotic syndromes.

PMID- 15841959
TI  - Detection of sub-optimal performance using a floor effect strategy in patients
      with traumatic brain injury.
AB  - This archival study examined the effectiveness of using a normative floor effect
      method to detect suboptimal performance in a clinical sample of 120 cases
      consecutively referred for a neuropsychological evaluation. These cases were
      divided into moderate-severe TBI, mild TBI, and poor effort litigants
      (demonstrating suboptimal effort). Percentiles, sensitivity, specificity,
      positive and negative predictive power, and overall correct classification rates
      were calculated using the moderate-severe TBI sample as the clinical reference
      group. Several levels of stringency for the floor effect using different base
      rates were also examined. Setting the floor at the 50th percentile consistently
      appeared to provide for the best overall hit rate when comparing cases with mild
      brain injury versus poor effort. At this level, a strong trend (greater than one
      third of total scores) toward the generation of positive scores offers compelling
      evidence that, in general, the neuropsychological data have been invalidated by
      poor motivation. Clinical implications are discussed.

PMID- 15841960
TI  - Screening of copper tolerant bacterial strains and their potential to remove
      copper from the environment.

PMID- 15841961
TI  - Effect of heavy metals on the activity of external carbonic anhydrase of
      microalga Chlamydomonas reinhardtii and microalgae from karst lakes.

PMID- 15841962
TI  - Effects of cadmium and zinc on the growth, food consumption, and nutritional
      conditions of the white shrimp, Litopenaeus vannamei (Boone).

PMID- 15841963
TI  - Toxicity of fluoride to the endangered unionid mussel, Alasmidonta raveneliana,
      and surrogate species.

PMID- 15841964
TI  - Cholinesterase activity in clam Meretrix casta: possible biomarker for
      organophosphate pesticide pollution.

PMID- 15841965
TI  - Regression comparisons of aquatic toxicity of benzene derivatives: Tetrahymena
      pyriformis and Rana japonica.

PMID- 15841966
TI  - Effects of dysprosium on the species-defined microbial microcosm.

PMID- 15841967
TI  - Multimedia evaluation of trace metal distribution within stormwater retention
      ponds in suburban Maryland, USA.

PMID- 15841968
TI  - Assessment of heavy metal residues in the sediment and water samples of Uluabat
      Lake, Turkey.

PMID- 15841969
TI  - Mercury in fish and shark tissues from two coastal lagoons in the Gulf of
      California, Mexico.

PMID- 15841970
TI  - Limpet, Patella caerulea Linnaeus, 1758 and barnacle, Balanus sp., as biomonitors
      of trace metal availabilities in Iskenderun Bay, northern East Mediterranean Sea.

PMID- 15841971
TI  - Trace elements in cultured tilapia (Oreochromis mossambicus): results from a farm
      in Southern Taiwan.

PMID- 15841972
TI  - Environmental lead exposure in the European kestrel (Falco tinnunculus) from
      southeastern Spain: the influence of leaded gasoline regulations.

PMID- 15841973
TI  - Bioaccumulation of heavy metals in vegetables from selected agricultural areas.

PMID- 15841974
TI  - Dietary influences on the bioaccumulation of pollutants by the annelid,
      Lumbriculus variegatus: experiments comparing artificial particles and natural
      sediments.

PMID- 15841975
TI  - Detection and quantification of insecticides in shrimp grown in a coastal farm in
      Sonora, Mexico.

PMID- 15841976
TI  - Multiresidue analysis of pesticides in animal feed concentrate.

PMID- 15841977
TI  - Biodegradation of imazapyr by free cells of Pseudomonas fluorescene biotype II
      and Bacillus cereus isolated from soil.

PMID- 15841978
TI  - Natural biodegradation of MTBE under different environmental conditions:
      microcosm and microbial identification studies.

PMID- 15841979
TI  - Photodegradation of 1,3,5-trichlorobenzene in aqueous surfactant solutions.

PMID- 15841980
TI  - Phthalate levels in baby milk powders sold in several countries.

PMID- 15841981
TI  - Urinary 3,5,6-trichloro-2-pyridinol levels of chlorpyrifos in Nicaraguan
      applicators and small farm families.

PMID- 15841982
TI  - Area and personal exposure measurements during asbestos abatement of a crawl
      space and boiler room.

PMID- 15841983
TI  - Worker exposure to diazinon during flea control operations in response to a
      plague epizootic.

PMID- 15841984
TI  - Environmental exposure to nitrated polycyclic aromatic hydrocarbons in the
      Taiwanese temple.

PMID- 15841985
TI  - DDT in human milk from Chiang Mai mothers: a public health perspective on
      infants' exposure.

PMID- 15841986
TI  - Human head hair as a tool in environmental pollution monitoring of Agra city.

PMID- 15841987
TI  - Air quality status and sources of PM10 in Kanpur city, India.

PMID- 15841988
TI  - Wind effects on passive air sampling of PAHs and PCBs.

PMID- 15841989
TI  - Osteogenic sarcoma of the mandible and maxilla: a Canadian review (1980-2000).
AB  - OBJECTIVE: To determine factors that influence survival in patients with
      osteogenic sarcoma of the jaws. STUDY DESIGN: Multicentre retrospective clinical
      pathologic study of 35 patients with osteogenic sarcoma of the jaws by the
      Canadian Society of Otolaryngology-Head and Neck Surgery Oncology Study Group.
      METHODS: Clinical charts and pathology results were reviewed on 35 patients
      treated between 1980 and 2000 for osteogenic sarcoma of the maxilla or mandible.
      Records were acquired from several major Canadian cancer registries. The
      following variables were examined for the effect on survival: age, gender, tumour
      site, grade and subtype, margins, and method of treatment. RESULTS: The average
      age of patients was 40 years (range 14-76 years). The sex distribution was
      similar, with 18 males and 17 females. The primary site was the mandible in 20
      patients and the maxilla in 15 patients. The overall survival was 79 +/- 7% at 2
      years and 57 +/- 9% at 5 years. Local recurrence (41%) was more common than
      distant metastases (17%). Positive margins were the factor most strongly
      associated with poor prognosis on multivariate analysis (hazard ratio = 3.5, p <
      .04). Disease-free survival dropped to zero by 3 years for those with positive
      margins (n = 7). For those who were resected with clear margins (n = 25), 5-year
      disease-free survival remained greater than 50% and the overall survival rate was
      almost 80%. Tumour site, grade, and subtype did not correlate with prognosis.
      There was a trend toward better prognosis in those who received chemotherapy in
      addition to surgery. CONCLUSION: Osteogenic sarcoma of the jaws is an aggressive
      disease with a high mortality rate despite a relatively low risk of distant
      metastases. Negative margins are paramount for optimizing survival rate.
      Chemotherapy, although contentious, should be considered given the data from long
      bone studies and the trend toward better survival in several studies, including
      ours.

PMID- 15841990
TI  - Bilateral cholesteatomas: the hospital for sick children experience.
AB  - OBJECTIVE: The purpose of this article is to review the cases of bilateral
      cholesteatomas in a tertiary care pediatric otolaryngology department. We compare
      the presenting signs and symptoms and timing of ipsilateral and contralateral
      cholesteatomas and the initial audiometric findings. METHODS: Retrospective chart
      review. SETTING: Department of Otolaryngology, The Hospital for Sick Children,
      Toronto, ON. RESULTS: Twenty-two patients with bilateral cholesteatomas were
      accrued. Nine patients had bilateral congenital cholesteatomas and presented at a
      substantially younger age than those with acquired disease (average of 5 years, 9
      months vs 11 years). Sixteen of the 22 patients were initially diagnosed with
      bilateral cholesteatomas. The majority of the remaining patients had evidence on
      initial assessment of contralateral middle ear disease. A particular subset of
      patients with severe disease requiring numerous bilateral revision surgeries was
      also identified. These patients also underwent revision surgery after a
      substantially shorter follow-up period. CONCLUSIONS: Bilateral cholesteatomas in
      the pediatric population are extremely rare. Bilateral congenital cholesteatomas
      are more common in males, whereas bilateral acquired cholesteatomas are more
      common in females. The outcome is generally poor. A small subset with
      particularly aggressive disease requires many more bilateral revision surgeries
      at an earlier period when compared with the remainder of the group.

PMID- 15841991
TI  - Skin breakdown over cochlear implants: prevention of a magnet site complication.
AB  - OBJECTIVE: To determine the prevalence of inflammation of the skin around the
      magnet of cochlear implants. METHOD: A postal survey of 232 children implanted at
      The Hospital for Sick Children, Toronto, detailing the timing and severity of
      skin inflammation near the magnet. RESULTS: Sixty-three children (27%) had at
      least one episode of skin erythema at the magnet site. In most cases, this
      resolved after reducing magnet field strength. Nine children stopped wearing the
      device briefly, and five were treated with antibiotics. Skin ulceration occurred
      in two cases. No surgical treatment was required. Reactions tended to occur in
      younger children (2.8 vs 4.3 years; p = .002, Mann-Whitney rank sum test).
      CONCLUSIONS: Skin inflammation commonly occurs in children between magnets of the
      transmitter and receiver coils of a cochlear implant. If inflammation fails to
      resolve after loosening the magnet, use of the implant should be discontinued
      temporarily. Antibiotics should be prescribed for cellulitis to prevent an
      implant-threatening infection.

PMID- 15841992
TI  - Reconstruction of old radical cavities and long-term results.
AB  - Various techniques and materials have been proposed to deal with the problems
      that concern radical cavities, such as recurrence of the inflammatory process,
      the need for regular medication, and social inconvenience (eg, inability to
      practice water sports, working in an adverse enviroment). This article provides a
      detailed report of the results of revalidation of old radical cavities using
      hydroxyapatite granules as a filling. The material was incorporated with fibrin
      adhesive to fill the mastoid cavity and was covered with a sheet of bone pate
      sealant. Twenty-eight patients with chronic discharging old radical cavities were
      selected for this study (mean follow-up 11.4 years; range 10-14 years). At the 6
      month follow-up, grafting was successful in 25 patients, whereas the functional
      outcomes showed an air-bone gap below 30 dB in 18 patients. No postoperative
      sensorineural hearing loss was observed. The long-term follow-up demonstrated a
      slight worsening of the initial findings; four other patients had reperforation
      of the tympanic membrane, and hearing deteriorated in five patients to above 30
      dB air-bone gap. These results could be a consequence of an alteration in the
      function of the eustachian tube and of the severity of the preoperative
      pathologic processes.

PMID- 15841993
TI  - Effects of middle ear application of Cipro HC Otic Suspension in an animal model.
AB  - The objective of this study was to examine whether ciprofloxacin-containing otic
      drops (Cipro HC Otic Suspension; 0.2% ciprofloxacin, 0.1% hydrocortisone; Alcon,
      Ontario, Canada) are cochleotoxic in the chinchilla animal model. Five
      chinchillas in total underwent these studies. Pretreatment distortion-product
      otoacoustic emissions (DPOAEs) were measured in each ear, followed by a random
      injection of Cipro to one ear and normal saline to the other. Injections
      consisted of 0.2 mL into the middle ear cavity (bulla) for 5 consecutive days.
      Post-treatment DPOAEs and auditory brainstem responses were measured at 1 month,
      and cochlear hair cell integrity was assessed by scanning electron microscopy
      (SEM). All animals had normal pretreatment DPOAEs. One month after Cipro
      instillation, DPOAE levels decreased in three of the animals. No significant
      change was seen in the ears treated with saline. On SEM examination, the
      integrity of the stereocilia of the inner and outer hair cells demonstrated no
      histologic evidence of significant cochlear damage. The finding of reduced DPOAEs
      suggests a mild local middle ear inflammation caused by the ciprofloxacin or some
      other component or property of Cipro.

PMID- 15841994
TI  - Far advanced otosclerosis: stapes surgery or cochlear implantation?
AB  - OBJECTIVE: Nowadays, two surgical alternatives are to be considered in patients
      with far advanced otosclerosis: stapedectomy and cochlear implantation. The aim
      of this study was to analyze and compare the hearing and communicative results
      obtained in two groups of patients affected with far advanced otosclerosis, who
      were treated with the two different surgical procedures, to assess the proper
      surgical approach for these patients. DESIGN: Retrospective study. SETTINGS:
      University hospital and referral audiologic centre. METHODS: We submitted 11
      adult patients, affected by far advanced otosclerosis and exhibiting
      unsatisfactory communicative abilities with hearing aids, to two different
      procedures: 5 to cochlear implantation, and 6 to stapedotomy followed by hearing
      aid fitting. The benefits afforded by the two procedures were assessed by means
      of pure-tone audiometry and speech audiometry in an open field and by means of a
      speech perception test. MAIN OUTCOME MEASURES: Hearing and communicative
      outcomes, measured 1 year after intervention. RESULTS: The results achieved in
      the patients subjected to stapedotomy were unpredictable and variable: very good
      in some cases but unsatisfactory in others, whereas those who had cochlear
      implantation all achieved satisfactory results with regard to speech recognition.
      CONCLUSIONS: Patients who underwent cochlear implantation achieved better hearing
      and communicative results than those who underwent stapedotomy. Even if the
      number of patients reported in this study is too small to provide definitive
      results, and despite the reportedly better results afforded by cochlear
      implantation, in our opinion, correction of far advanced otosclerosis should
      first be attempted via stapedotomy, and cochlear implantation should instead be
      reserved for cases in which stapedotomy is unsuccessful or for which imaging
      techniques unequivocally reveal a fenestral or cochlear obstruction.

PMID- 15841995
TI  - Snoring and obstructive sleep apnea: compliance with oral appliance therapy.
AB  - OBJECTIVE: To assess the effectiveness of oral appliances in clinical practice.
      DESIGN: Survey of 110 subjects. SETTING: Hospital-based dental practice. METHODS:
      Questionnaire. MAIN OUTCOME MEASURES: Compliance and control of sleepiness and
      snoring. RESULTS: Fifty-seven percent of respondents were compliant with therapy,
      reporting control of sleepiness and snoring. CONCLUSIONS: More than 50% of those
      on oral appliance therapy reported continued use after at least 18 months.

PMID- 15841996
TI  - Deroofing surgical treatment for pseudocyst of the auricle.
AB  - OBJECTIVES: Pseudocyst of the auricle is characterized by asymptomatic swelling
      caused by an intracartilaginous accumulation of fluid. If left untreated,
      permanent deformity of the pinna may occur. Many modalities of treatment have
      been reported, but problems regarding recurrence and appearance remain. The
      purpose of this study was to introduce more reliable treatment for pseudocyst of
      the auricle. DESIGN: Retrospective chart review. SETTING: Department of
      Otolaryngology, Kaohsiung Medical University, Kaohsiung, Taiwan. METHODS: The
      population used for the present report consisted of 10 patients with auricular
      pseudocyst that was unresponsive to aspiration followed by intralesional steroid
      injection or who declined conservative treatment. All patients were treated
      surgically with the deroofing method under local anaesthesia. MAIN OUTCOME
      MEASURES: Postoperative clinical outcome and recurrence of the lesion. RESULTS:
      All patients had excellent cosmetic outcomes, and no recurrence or complication
      occurred. CONCLUSIONS: Deroofing surgery for pseudocyst of the auricle is a safe,
      easy, and reliable procedure. If conservative measures fail or are declined by
      the patient, removal of the anterior cartilaginous leaflet of the lesion is an
      alternative method that can yield excellent results.

PMID- 15841997
TI  - Recurrent pleomorphic adenoma of the parotid gland.
AB  - This is a retrospective analysis of 35 patients treated for a first recurrence of
      pleomorphic adenoma of the parotid gland from 1982 to 1997. All patients were
      treated surgically; no patient received radiotherapy for benign disease. We
      experienced a locoregional control rate of 77%. Our malignant transformation rate
      was 5.7%. Our results suggest that in carefully selected patients, local excision
      of recurrent disease is sufficient in controlling further recurrence.

PMID- 15841998
TI  - Early operative intervention versus conventional treatment in epistaxis:
      randomized prospective trial.
AB  - OBJECTIVE: This prospective randomized trial was designed to compare intranasal
      endoscopic sphenopalatine artery ligation (ESAL) with conventional nasal packing
      in the treatment of recurrent epistaxis. METHODS: Patients were registered in the
      study databank following referral for epistaxis control to the otolaryngology
      service at the University of Alberta. All patients were initially packed using
      Merocel (Xomed Surgical Products, Jacksonville, FL) nasal dressings bilaterally.
      Patients were enrolled in the study following failure of Merocel packings.
      Informed consent was obtained in accordance with the Health Research Ethics
      Board. The patients were then managed with Vaseline nasal packs or ESAL. Patient
      demographics, treatment characteristics, number of hospitalization days, and
      rates of recurrence were recorded prospectively. The total cost of treatment for
      each patient was calculated. RESULTS: Nineteen patients were enrolled in the
      study. There was a significant reduction in cost and length of hospitalization of
      the patients undergoing ESAL compared with the conventional nasal packings. ESAL
      was also 89% effective in controlling the bleeding and had minimal sequelae or
      complications. The overall calculated cost of patients undergoing ESAL was
      dollars 5133 compared with dollars 12213 in the conservative group, resulting in
      an average saving of dollars 7080 per patient. There was overwhelming patient
      satisfaction with ESAL compared with nasal packings. CONCLUSION: ESAL is an
      excellent, well-tolerated, and cost-effective method of treating recurrent
      epistaxis.

PMID- 15841999
TI  - Connexin mutation testing of children with nonsyndromic, autosomal recessive
      sensorineural hearing loss.
AB  - OBJECTIVE: The etiology of hearing loss is heterogeneous and falls into the two
      broad categories of genetic and environmental. In the genetic subgroup, 70% are
      non syndromic. Fifty percent of nonsyndromic sensorineural deafness is due to a
      mutation in the connexin 26 gene. This article presents the detection rate of
      connexin mutations in a multiethnic Canadian population. METHODS: A study of
      patients with nonsyndromic hearing loss seen over a period of 2 years who had
      connexin 26 mutation testing. RESULTS: Nine of the 18 patients had connexin 26
      mutations. CONCLUSION: The majority of our patients with connexin 26 mutations
      had moderate to profound hearing loss. Testing for connexin mutations should be
      standard care because it accounts for a large proportion of individuals with
      nonsyndromic hearing loss. Reasons for testing include ruling out a syndromic
      cause, predicting moderate to profound hearing loss, and the need for language
      intervention, cochlear implants, and genetic counselling.

PMID- 15842000
TI  - A safe way to remove a ruptured thyroglossal duct cyst.

PMID- 15842001
TI  - Giant cell tumour of the larynx: case report and review of the literature.

PMID- 15842003
TI  - Hypopharyngeal perforation after blunt neck trauma.

PMID- 15842002
TI  - Epidermotropic cutaneous metastases from hypopharyngeal carcinoma.
AB  - Cutaneous metastases from laryngeal and hypopharyngeal squamous carcinomas are
      extremely rare. A high index of clinical suspicion, supplemented with
      histopathologic evidence, aids in the diagnosis. The prognosis is extremely poor,
      and treatment is aimed only at palliation of symptoms and improving quality of
      life.

PMID- 15842004
TI  - Sinonasal teratocarcinosarcoma.

PMID- 15842005
TI  - Hemorrhagic pseudotumour of the maxillary sinus.

PMID- 15842006
TI  - Speech intelligibility of pediatric cochlear implant recipients with 7 years of
      device experience.
AB  - Speech intelligibility of 24 prelingually deaf pediatric cochlear implant (CI)
      recipients with 84 months of device experience was investigated. Each CI
      participant's speech samples were judged by a panel of 3 listeners.
      Intelligibility scores were calculated as the average of the 3 listeners'
      responses. The average write-down intelligibility score was 71.54% (SD = 29.89),
      and the average rating-scale intelligibility score was 3.03 points (SD = 1.01).
      Write-down and rating-scale intelligibility scores were highly correlated (r =
      .91, p < .001). Linear regression analyses revealed that both age at implantation
      and different speech-coding strategies contribute to the variability of CI
      participants' speech intelligibility. Implantation at a younger age and the use
      of the spectral-peak speech-coding strategy yielded higher intelligibility scores
      than implantation at an older age and the use of the multipeak speech-coding
      strategy. These results serve as indices for clinical applications when long-term
      advancements in spoken-language development are considered for pediatric CI
      recipients.

PMID- 15842007
TI  - Auditory temporal pattern discrimination and reading ability.
AB  - The relation between reading ability and performance on an auditory temporal
      pattern discrimination task was investigated in children who were either good or
      delayed readers. The stimuli in the primary task consisted of sequences of tones,
      alternating between high and low frequencies. The threshold interstimulus
      interval (ISI) for discrimination of differences in the temporal properties of
      the sequences was measured. An ISI threshold was also measured in a control task
      that was identical to the primary task, except all tones in a control sequence
      had the same frequency. Delayed readers and good readers were equally able to
      discriminate the timing of the sequences at short ISIs, for both the primary and
      control tasks. Furthermore, the ISI thresholds were not correlated with the
      ability to read either irregular words or nonwords. These results suggest that
      reading ability is not related to the ability to track large and rapid frequency
      changes in auditory temporal patterns.

PMID- 15842008
TI  - Phonologic processing in adults who stutter: electrophysiological and behavioral
      evidence.
AB  - Event-related brain potentials (ERPs), judgment accuracy, and reaction times
      (RTs) were obtained for 11 adults who stutter and 11 normally fluent speakers as
      they performed a rhyme judgment task of visually presented word pairs. Half of
      the word pairs (i.e., prime and target) were phonologically and orthographically
      congruent across words. That is, the words looked orthographically similar and
      rhymed (e.g., thrown, own) or did not look similar and did not rhyme (e.g., cake,
      own). The phonologic and orthographic information across the remaining pairs was
      incongruent. That is, the words looked similar but did not rhyme (e.g., gown,
      own) or did not look similar but rhymed (e.g., cone, own). Adults who stutter and
      those who are normally fluent exhibited similar phonologic processing as indexed
      by ERPs, response accuracy, and RTs. However, longer RTs for adults who stutter
      indicated their greater sensitivity to the increased cognitive loads imposed by
      phonologic/orthographic incongruency. Also, unlike the normally fluent speakers,
      the adults who stutter exhibited a right hemisphere asymmetry in the rhyme
      judgment task, as indexed by the peak amplitude of the rhyming effect (difference
      wave) component. Overall, these findings do not support theories of the etiology
      of stuttering that posit a core phonologic-processing deficit. Rather we provide
      evidence that adults who stutter are more vulnerable to increased cognitive loads
      and display greater right hemisphere involvement in late cognitive processes.

PMID- 15842009
TI  - The distinctness of speakers' /s/-/S/ contrast is related to their auditory
      discrimination and use of an articulatory saturation effect.
AB  - This study examines individual differences in producing the sibilant contrast in
      American English and the relation of those differences to 2 speaker
      characteristics: (a) use of a quantal biomechanical effect (called a "saturation
      effect") in producing the sibilants and (b) performance on a test of sibilant
      discrimination. Twenty participants produced the sibilants /s/ and /S/ in normal
      , clear-, and fast-speaking conditions. The degree to which the participants used
      a saturation effect in producing /s/ and /S/ was assessed with a custom-made
      sensor that measured contact of the underside of the tongue tip with the lower
      alveolar ridge; such contact normally occurs during the production of /s/ but not
      /S/. The acuteness of the participants' discrimination of the sibilant contrast
      was measured using the ABX paradigm and synthesized sibilants. Differences among
      speakers in the degree of acoustic contrast between /s/ and /S/ that they
      produced proved related to differences among them in their use of contact
      contrastively and in their discriminative performance. The most distinct sibilant
      productions were obtained from participants who used contact in producing /s/ but
      not /S/ and who had high discrimination scores. The participants who did not use
      contact differentially when producing the 2 sibilants and who also discriminated
      the synthetic sibilants less well produced the least distinct sibilant contrasts.
      Intermediate degrees of sibilant contrast were found with participants who used
      contact differentially or discriminated well. These findings are compatible with
      a model of speech motor planning in which goals for phonemic speech movements are
      in somatosensory and auditory spaces.

PMID- 15842010
TI  - Trade-offs between informativeness and speed of message delivery in augmentative
      and alternative communication.
AB  - This report is the second in a series of investigations designed to develop a
      working model identifying the effects of trade-offs between selected
      conversational maxims on public attitudes toward augmentative and alternative
      communication (AAC) system users and their communication. In the current study,
      tradeoffs between the informativeness of a prestored message and its speed of
      delivery were examined. A total of 96 salesclerks participated. Sixteen scripted,
      videotaped conversational conditions, involving an AAC customer and a clerk at a
      checkout counter, were used to manipulate message informativeness and speed of
      message delivery. Following each assigned viewing, participants completed a
      questionnaire designed to assess their attitudes toward the AAC user and his or
      her communication. The conditions involving (a) the quickly delivered message
      with excessive information, (b) the slowly delivered message with adequate
      information preceded by a "floorholder," and (c) the slowly delivered message
      with adequate information without a floorholder were rated higher than (d) the
      quickly delivered message with inadequate information. There was no main effect
      for participant or AAC user gender. Implications regarding a model of
      conversational trade-offs and technological applications are discussed.

PMID- 15842011
TI  - Fast mapping of words and story recall by individuals with Down syndrome.
AB  - This study compared adolescents with Down syndrome to nonverbal mental-age
      matched controls in their ability to fast map new noun vocabulary in spoken story
      contexts. Context for novel words varied within subjects in the distance between
      mentions (close-distant) and the ease of inferring a real word for the referent
      (specificity). The 23 participants with Down syndrome (DS) were aged 12.8-20.3
      years. The 24 typically developing (TD) children, matched on visual nonverbal
      mental age (MA), were 4.1 to 6.1 years old. Participants listened to 4 tape
      recorded stories, each containing 3 mentions of 2 novel words in close or distant
      proximity and with clear or uncertain reference, and recalled each story after
      presentation. Fast-mapping production was measured by the occurrence of the novel
      word in story recall. Fast-mapping comprehension was measured by asking children
      to define the novel words. The DS group did not differ from the TD group in novel
      word production but seemed to have more difficulty with novel word definition.
      For both groups, novel word production was higher in the nonspecific than the
      specific referent condition, suggesting that availability of a real word label
      interfered with fast mapping. Recall of story propositions was poorer for the DS
      group. For both groups, story recall was better for text units not directly
      associated with novel words than for text units containing novel words,
      suggesting a trade-off effect in processing. Regression analyses indicated that
      syntax comprehension, rather than mean length of utterance, predicted novel word
      production in both groups; MA additionally contributed to predict DS story
      recall.

PMID- 15842012
TI  - Oral and written story composition skills of children with language impairment.
AB  - In this study 538 children composed 1 oral and 1 written fictional story in both
      2nd and 4th grades. Each child represented 1 of 4 diagnostic groups: typical
      language (TL), specific language impairment (SLI), nonspecific language
      impairment (NLI), or low nonverbal IQ (LNIQ). The stories of the TL group had
      more different words, more grammatical complexity, fewer errors, and more overall
      quality than either language-impaired group at either grade. Stories of the SLI
      and LNIQ groups were consistently stronger than were those of the NLI group.
      Kindergarten children with language impairment (LI) whose standardized test
      performance suggested normalization by 2nd grade also appeared to have recovered
      in storytelling abilities at that point. By 4th grade, however, these children's
      stories were less like the children with TL and more like those of children with
      persistent LI than they had been in 2nd grade. Oral stories were better than
      written stories in both grades, although the greatest gains from 2nd to 4th grade
      were generally made on written stories. Girls told stronger stories than did boys
      at both grades, regardless of group placement. It is concluded that story
      composition tasks are educationally relevant and should play a significant role
      in the evaluation of children with developmental LI.

PMID- 15842013
TI  - A dense corpus study of past tense and plural overregularization in English.
AB  - In the "blocking-and-retrieval-failure" account of overregularization (OR; G. F.
      Marcus, 1995; G. F. Marcus et al., 1992), the claim that a symbolic rule
      generates regular inflection is founded on pervasively low past tense OR rates
      and the lack of a substantive difference between past tense and plural OR rates.
      Evidence of extended periods of OR in the face of substantial correct input (M.
      Maratsos, 2000) and of an initial period in which nouns are more likely to be
      overregularized than verbs (V. A. Marchman, K. Plunkett, & J. Goodman, 1997)
      casts doubt on the blocking account and suggests instead an interplay between
      type and token frequency effects that is more consistent with usage-based
      approaches (e.g., J. Bybee, 1995; K. Kopcke, 1998; K. Plunkett & V. Marchman,
      1993). However, previous naturalistic studies have been limited by data that
      account for only 1-2% of child speech. The current study reports analyses of verb
      and noun ORs in a dense naturalistic corpus (1 child, 2;00.12-3;11.06
      [years;months.days]) that captures 8-10% of child speech and input. The data show
      (a) a marked difference in verb and noun OR rates; (b) evidence of a relationship
      between relative regular/irregular type frequencies and the onset and rate of
      past tense and plural ORs; (c) substantial OR periods for some verbs and nouns
      despite hundreds of correct tokens in child speech and input; and (d) a strong
      negative correlation between input token frequencies and OR rates for verbs and
      nouns. The implications of these findings for blocking and other accounts of OR
      are discussed.

PMID- 15842014
TI  - Language influences on verbal short-term memory performance in Down syndrome:
      item and order recognition.
AB  - Down syndrome is associated with severe deficits in language and verbal shortterm
      memory, but the causal relationship between these deficits is unclear. The
      current study therefore investigated the influence of language abilities on
      verbal short-term memory performance in Down syndrome. Twenty-one individuals
      with Down syndrome and 29 younger typically developing children were tested on
      memory for words and nonwords using 2 immediate recognition tasks: an order
      memory task that was a relatively pure measure of verbal short-term memory and an
      item memory task that was more sensitive to language ability. Despite having
      superior vocabulary knowledge to the typically developing children, individuals
      with Down syndrome were impaired on both order and item tasks. This impairment
      was particularly marked on the item task, where individuals with Down syndrome
      showed an atypically large lexicality effect. These results are interpreted in
      terms of an underlying verbal short-term memory deficit in Down syndrome that is
      compounded by poor phonological discrimination abilities.

PMID- 15842015
TI  - Simulating SLI: general cognitive processing stressors can produce a specific
      linguistic profile.
AB  - This study attempted to model specific language impairment (SLI) in a group of 6
      year-old children with typically developing language by introducing cognitive
      stress factors into a grammaticality judgment task. At normal speech rate, all
      children had near-perfect performance. When the speech signal was compressed to
      50% of its original rate, to simulate reduced speed of processing, children
      displayed the same pattern of errors that is reported in SLI: good performance on
      noun morphology (plural -s) and very poor performance on verb morphology (past
      tense -ed and 3rd-person singular -s). A similar pattern was found when memory
      load was increased by adding redundant verbiage to sentence stimuli. The finding
      that an SLI-like pattern of performance can be induced in children with intact
      linguistic systems by increasing cognitive processing demands supports the idea
      that a processing deficit may underlie the profile of language difficulty that
      characterizes SLI.

PMID- 15842016
TI  - Tense and agreement in the speech of children with specific language impairment:
      patterns of generalization through intervention.
AB  - Thirty-one children with specific language impairment participated in 48
      intervention sessions designed to assist them in the use of 3rd-person singular 
      s or auxiliary is/are/was. Gains in the use of these target forms were
      significantly greater than gains on developmentally comparable morphemes serving
      as control forms. Untreated verb forms that mark both tense and agreement showed
      greater change during the intervention period than did past -ed. The findings
      suggest that by gaining skill in the use of morphemes that mark both tense and
      agreement, the children were able to identify and acquire other morphemes in the
      language that mark both of these features. This increase in sensitivity did not
      appear to apply to forms in the language that express tense only.

PMID- 15842017
TI  - Inference generation during text comprehension by adults with right hemisphere
      brain damage: activation failure versus multiple activation.
AB  - Evidence conflicts as to whether adults with right hemisphere brain damage (RHD)
      generate inferences during text comprehension. M. Beeman (1993) reported that
      adults with RHD fail to activate the lexical-semantic bases of routine bridging
      inferences, which are necessary for comprehension. But other evidence indicates
      that adults with RHD activate multiple interpretations in various comprehension
      domains. In addition, the activation of contextually inappropriate
      interpretations is prolonged for many adults with RHD and predicts poor discourse
      comprehension. This study contrasted Beeman's activation failure hypothesis with
      the prediction that adults with RHD would generate multiple interpretations in
      text comprehension. The relation between activation of textually incompatible
      inferences and discourse comprehension was also investigated for this group.
      Thirty-seven adults with RHD and 34 without brain damage listened to brief
      narratives that required a bridging inference (BI) to integrate the text-final
      sentence. This final sentence, when isolated from its text, was strongly biased
      toward a contextually incompatible alternate interpretation (AI). Auditory
      phoneme strings were presented for lexical decision immediately after each text's
      initial and final sentence. Adults with RHD were both faster and more accurate in
      making lexical decisions to BI-related target words in final-sentence position
      than in initial-sentence position. Thus, contrary to the activation failure
      hypothesis, adults with RHD generated the lexical-semantic foundations of BIs
      where they were required by the text. AI generation was evident in accuracy data
      as well, but not in response time data. This result is partially consistent with
      the multiple activation view. Finally, greater activation for contextually
      incompatible interpretations was associated with poorer discourse comprehension
      performance by adults with RHD.

PMID- 15842018
TI  - Utterance length and lexical diversity in Cantonese-speaking children with and
      without specific language impairment.
AB  - Two studies of children's conversational language abilities are reported. In the
      first, mean length of utterance (MLU) and lexical diversity (D) were examined in
      a group of typically developing Cantonese-speaking children in Hong Kong.
      Regression analyses indicated a significant linear relationship between MLU and
      age (R = .44) and a significant curvilinear relationship between D and age (R =
      .73) in children age 27-68 months. MLU and D were moderately correlated with each
      other (r = .23); however, the two measures showed no statistical relationship
      when the effect of age was partialled out. In a second study, the utterances of
      Chinese children with specific language impairment (SLI) were found to be
      significantly shorter and less lexically diverse than typically developing
      children matched for age but similar to children matched for comprehension level.
      Discriminant analyses revealed that the combination of age, MLU, and D could be
      used to accurately differentiate children with SLI from both age-matched and
      language-matched children. Based on these findings, we hypothesize that these
      measures can be used jointly as a marker of SLI in Cantonese-speaking children.

PMID- 15842019
TI  - Subtypes of severe speech and language impairments: psychometric evidence from 4
      year-old children in The Netherlands.
AB  - Most, if not all, of the studies of subtypes of children with language
      impairments have been conducted with English-speaking children. The possibility
      and validity of identified subtypes for non-English clinical populations are, as
      yet, unknown. This study was designed to provide cross-linguistic evidence of
      language subtypes. A broad battery of tests was administered to measure the
      phonological, lexical, morphosyntactic, semantic, discourse, and pragmatic
      abilities of a representative sample of 110 4-year-old Dutch children who had
      been previously diagnosed as severely speech and language impaired. Principal
      components analyses revealed 4 subtypes of speech and language impairments, which
      were labeled lexical-semantic, speech production, syntoctic-sequential, and
      auditory perception. These results were consistent with recent theoretical claims
      about the classification of English-speaking children with speech and language
      impairments.

PMID- 15842020
TI  - The effects of direct instruction on the single-word reading skills of children
      who require augmentative and alternative communication.
AB  - Current literature suggests a lack of empirically validated strategies for
      teaching reading skills to children who use augmentative and alternative
      communication (AAC). The current study implemented a single-subject, multiple
      probe-across-subjects design to investigate the effects of direct instruction in
      single-word reading on the performance of students who use AAC. The instructional
      program targeted the reading skills of 5 participants who had severe speech
      impairments and ranged in age from 9 to 14 years old. All 5 participants reached
      criterion for matching targeted written words to corresponding pictures. Three of
      the 5 participants demonstrated generalization of reading skills to novel-word
      reading, and 4 of the 5 generalized reading skills to book contexts. Implications
      and directions for future research are discussed.

PMID- 15842021
TI  - Questions without movement: A study of Cantonese-speaking children with and
      without specific language impairment.
AB  - English-speaking children with specific language impairment (SLI) appear to have
      special difficulty in the use of who-object questions (e.g., Who is the girl
      chasing?). It has been argued that problems related to grammatical movement may
      be responsible for this difficulty. However, it is also possible that the lower
      frequency of who-object questions relative to who-subject questions also plays a
      role. In this study, the use of who-object and who-subject questions by children
      with SLI who were acquiring Cantonese as their 1 st language was examined. In
      Cantonese, the surface form of who-object questions (e.g., hung4zai2 sek3
      bin1go3? [Bear kiss who?]) reflects the same subject, verb, object order
      typically used for declarative sentences, and a movement account provides no
      basis for expecting special difficulties with such questions. As in English,
      however, Cantonese who-object questions occur less frequently than do who-subject
      questions. A comparison of preschoolers with SLI, typically developing same-age
      peers, and younger, typically developing peers revealed that the children with
      SLI were less accurate in using who-object questions than either of the other
      participant groups yet showed no differences from these groups in the use of who
      subject questions (e.g., bin1go3 sek3 zyu1zyu1? [Who kiss Piglet?]). The
      implications of these findings for current accounts of SLI are discussed, and the
      idea that input frequency and animacy may play a larger role than is often
      assumed is suggested.

PMID- 15842022
TI  - Methods for minimizing the confounding effects of word length in the analysis of
      phonotactic probability and neighborhood density.
AB  - Recent research suggests that phonotactic probability (the likelihood of
      occurrence of a sound sequence) and neighborhood density (the number of words
      phonologically similar to a given word) influence spoken language processing and
      acquisition across the lifespan in both normal and clinical populations. The
      majority of research in this area has tended to focus on controlled laboratory
      studies rather than naturalistic data such as spontaneous speech samples or
      elicited probes. One difficulty in applying current measures of phonotactic
      probability and neighborhood density to more naturalistic samples is the
      significant correlation between these variables and word length. This study
      examines several alternative transformations of phonotactic probability and
      neighborhood density as a means of reducing or eliminating this correlation with
      word length. Computational analyses of the words in a large database and
      reanalysis of archival data supported the use of z scores for the analysis of
      phonotactic probability as a continuous variable and the use of median
      transformation scores for the analysis of phonotactic probability as a
      dichotomous variable. Neighborhood density results were less clear with the
      conclusion that analysis of neighborhood density as a continuous variable
      warrants further investigation to differentiate the utility of z scores in
      comparison to median transformation scores. Furthermore, balanced dichotomous
      coding of neighborhood density was difficult to achieve, suggesting that analysis
      of neighborhood density as a dichotomous variable should be approached with
      caution. Recommendations for future application and analyses are discussed.

PMID- 15842023
TI  - The nature of written language deficits in children with SLI.
AB  - Children with specific language impairment (SLI) have associated difficulties in
      reading decoding and reading comprehension. To date, few research studies have
      examined the children's written language. The aim of the present study was to (a)
      evaluate the nature and extent of the children's difficulties with writing and
      (b) investigate the relationship between oral and written language. Eleven
      children with SLI were identified (mean age = 11 years) and were compared with a
      group of children matched for chronological age (CA; mean age = 11;2
      [years;months]) and language age (LA; mean CA = 7;3). All groups completed
      standardized measures of language production, writing, and reading decoding. The
      writing assessment revealed that the SLI group wrote fewer words and produced
      proportionately more syntax errors than the CA group, but they did not differ on
      a measure of content of written language or on the proportion of spelling errors.
      The SLI group also produced proportionately more syntax errors than the LA group.
      The relationships among oral language, reading, and writing differed for the 3
      groups. The nature and extent of the children's written language problems are
      considered in the context of difficulties with spoken language.

PMID- 15842024
TI  - The cognitive neuropsychiatry of delusions: from psychopathology to
      neuropsychology and back again.
AB  - BACKGROUND: The nature of delusions remains unclear despite their interest to
      researchers and importance in psychopathology. Here we present a review of the
      contributions from various disciplines, principally cognitive neuroscience,
      towards a new understanding. METHOD: Narrative review of published research.
      RESULTS: The main areas of activity revolve around reasoning biases,
      attributional and attentional biases, theory of mind, and the role of emotion,
      with each area beginning to be explored using functional neuroimaging techniques.
      Of heuristic interest are neurological models, which include confabulation and
      delusional misidentification and the one- versus two-stage (perceptual versus
      reasoning plus perceptual) accounts of the latter. CONCLUSIONS: These different
      approaches are shown to each highlight mechanisms which are suggested to cause,
      contribute to, or modulate the genesis and form of delusions. Such contributions
      coupled with traditional phenomenological methods should provide the foundations
      for a cognitive neuropsychiatry of delusions.

PMID- 15842025
TI  - Randomized trial of a population-based care program for people with bipolar
      disorder.
AB  - BACKGROUND: Despite the availability of efficacious medications and
      psychotherapies, care of bipolar disorder in everyday practice is often
      deficient. This trial evaluated the effectiveness of a multi-component care
      management program in a population-based sample of people with bipolar disorder.
      METHOD: Four hundred and forty-one patients treated for bipolar disorder during
      the prior year were randomly assigned to continued usual care or usual care plus
      a systematic care management program including: initial assessment and care
      planning, monthly telephone monitoring including brief symptom assessment and
      medication monitoring, feedback to and coordination with the mental health
      treatment team, and a structured group psychoeducational program--all provided by
      a nurse care manager. Blinded quarterly assessments generated week-by-week
      ratings of severity of depression and mania symptoms using the Longitudinal
      Interval Follow-Up Evaluation. RESULTS: Participants assigned to the intervention
      group had significantly lower mean mania ratings averaged across the 12-month
      follow-up period (Z= 2.44, p=0.015) and approximately one-third less time in
      hypomanic or manic episode (2.59 weeks v. 1.69 weeks). Mean depression ratings
      across the entire follow-up period did not differ significantly between the two
      groups, but the intervention group showed a greater decline in depression ratings
      over time (Z statistic for group-by-time interaction = 1.98, p = 0.048).
      CONCLUSIONS: A systematic care program for bipolar disorder significantly reduces
      risk of mania over 12 months. Preliminary results suggest a growing effect on
      depression over time, but longer follow-up will be needed.

PMID- 15842026
TI  - A cluster randomized trial comparing two interventions to improve treatment of
      major depression in primary care.
AB  - BACKGROUND: Many patients with major depression are non-adherent to
      antidepressant medication and do not receive care according to current
      guidelines. There is increasing evidence that treatment of depression in primary
      care can be improved. Comparison between effective interventions may help to
      establish the active ingredients of such interventions. METHOD: In a randomized
      trial two interventions to improve treatment of major depression in primary care
      were compared (1) a depression care programme, targeting general practitioners
      (GPs), patients, and systematic follow-up, and (2) a systematic follow-up
      programme. Thirty GPs were randomized and 211 primary-care patients with current
      major depression were included. All patients were prescribed a selective
      serotonin reuptake inhibitor. Outcome measures included adherence to
      antidepressant medication, and depression outcome. RESULTS: No significant
      differences in adherence rates and treatment outcome measures were demonstrated
      between interventions at week 10 or week 26. Adherence rates were high and
      treatment outcome was favourable. CONCLUSIONS: The depression care programme was
      not superior to the systematic follow-up programme. Systematic follow-up in
      depression treatment in primary care seems to be an intervention per se, having
      the potential to improve adherence and treatment outcome.

PMID- 15842028
TI  - Dose-effect relations in time-limited combined psycho-pharmacological treatment
      for depression.
AB  - BACKGROUND: A limited number of psychotherapy sessions in combination with
      medication is preferable to pharmacotherapy only in the treatment of ambulatory
      patients with major depression. Whether there is a relation between the number of
      sessions and the efficacy of the treatment is uncertain. METHOD: Randomized
      clinical trial comparing two treatment conditions in outpatients with major
      depression. All patients studied had a baseline score of at least 14 points on
      the 17-item Hamilton Depression Rating Scale. The two conditions consist of 8
      session or 16-session Short Psychodynamic Supportive Psychotherapy, both in
      combination with pharmacotherapy. Efficacy was assessed using the 17-item HDRS,
      the CGI of Severity and of Improvement, the depression subscale of the SCL-90 and
      the Quality of Life Depression Scale. RESULTS: The rate of change would seem to
      indicate that eight sessions are preferable for both moderately and severely
      depressed patients, although the results converged again at the end. Furthermore,
      in terms of satisfaction with the number of sessions and drop-out percentages
      during treatment, no differences were found between the conditions. CONCLUSION:
      In the light of the outcome analysis (faster remission after fewer sessions), a
      short version of the psychotherapy treatment in a combined course of treatment
      seems to be justified.

PMID- 15842027
TI  - Training Latin American primary care physicians in the WPA module on depression:
      results of a multicenter trial.
AB  - BACKGROUND: In order to improve care for people with depressive disorders and to
      reduce the increasing burden of depression, the American Regional Office of the
      World Health Organization has launched a major region-wide initiative. A central
      part of this effort was directed to the primary care system where the diagnosis
      and treatment of depression are deficient in many countries. This study evaluated
      the materials developed by the World Psychiatric Association in a training
      program on depression among primary care physicians by measuring changes in their
      knowledge, attitudes, and practice (KAP). METHOD: One hundred and seven
      physicians and 6174 patients from five Latin American countries participated in
      the trial. KAP were assessed 1 month before and 1 month following the training
      program. In addition, the presence of depressive symptoms was measured in
      patients who visited the clinic during a typical week at both times using the
      Zung Depression Scale and a DSM-IV/ ICD-10 major depression checklist. RESULTS:
      The program slightly improved knowledge about depression and modified some
      attitudes, but had limited impact on actual practice. There was no evidence that
      the diagnosis of depression was made more frequently, nor was there an
      improvement in psychopharmacological management. The post-training agreement
      between physician diagnosis and that based on patient self-report remained low.
      The physicians, however, seemed more confident in treating depressed patients
      after training, and referred fewer patients to psychiatrists. CONCLUSIONS:
      Traditional means of training primary care physicians in depression have little
      impact on clinical practice regardless of the quality of the teaching materials.

PMID- 15842029
TI  - Duration of relapse prevention after cognitive therapy in residual depression:
      follow-up of controlled trial.
AB  - BACKGROUND: Although there is good evidence that cognitive therapy (CBT) lessens
      relapse and recurrence in unipolar depression, the duration of this effect is not
      known. METHOD: One hundred and fifty-eight subjects, from a randomized controlled
      trial of CBT plus medication and clinical management versus medication and
      clinical management alone, were followed 6 years after randomization (4 1/2 years
      after completion of CBT) and the longitudinal course assessed. RESULTS: Effects
      in prevention of relapse and recurrence were found to persist, with weakening,
      and were not fully lost until 3 1/2 years after the end of CBT. Residual symptoms
      were also lessened. CONCLUSIONS: The effect of CBT in reduction of relapse and
      recurrence persists for several years. The potential value of subsequent
      additional CBT some time after cessation should be explored.

PMID- 15842030
TI  - Sense of hyper-positive self and response to cognitive therapy in bipolar
      disorder.
AB  - INTRODUCTION: Cognitive therapy (CT) for bipolar disorder emphasizes the
      monitoring and regulation of mood, thoughts and behaviour. The Sense of Hyper
      Positive Self Scale (SHPSS) measures the extent to which bipolar patients value
      themselves and perceive themselves to possess personal attributes (e.g. dynamism,
      persuasiveness and productiveness) associated with a state of being 'mildly
      high', which does not reach the severity of clinical hypomania. It is
      hypothesized that patients who score highly on the SHPSS do not respond well to
      cognitive therapy. METHOD: One hundred and three bipolar-I patients were
      randomized into CT and control groups. The SHPSS was administered at baseline and
      at a 6-month follow-up. RESULT: The SHPSS had good test-retest reliability after
      6 months. At baseline, the Goal-Attainment Dysfunctional Attitudes contributed
      significantly to the SHPSS scores after the mood measures were controlled for in
      a regression analysis. There was a significant interaction between baseline SHPSS
      scores and group allocation in predicting relapse during therapy. Patients who
      scored highly on the SHPSS had a significantly increased chance of relapse after
      controlling for mood scores, levels of social functioning at recruitment, and the
      previous number of bipolar episodes. CONCLUSION: Not all patients benefited from
      CT. For patients with high SHPSS scores, CT was less efficacious. The results
      also indicate that future studies could evaluate targeting these attributes and
      dysfunctional beliefs with intensive cognitive behavioural techniques.

PMID- 15842031
TI  - Five-year outcome of outpatient psychotherapy with borderline patients.
AB  - BACKGROUND: Borderline personality disorder (BPD) is a serious mental illness.
      Due to scepticism about the effectiveness of its treatment, the care of these
      patients is neglected. In this study we evaluated the effect of treatment 5 years
      after its ending, of patients with BPD. METHOD: Thirty subjects were treated
      twice weekly for 1 year by psychotherapy based on the 'Conversational Model' of
      Hobson. Outcome measures included time in hospital, number of episodes of
      violence and self-harm, number of medical appointments, drug use and work
      history. A 'morbidity budget' made up of these items was collated for the year
      before treatment, the year following treatment, and for the year preceding the 5
      year follow-up. Additional measures included DSM-III criteria and a self-report
      of symptoms. These outcomes were compared to a hypothetical natural history of
      BPD constructed from the DSM scores of 150 borderline patients aged between 18
      and 52 years. RESULTS: Except for one measure, the improvements evident 1 year
      following treatment were maintained 4 years later. This improvement was not
      predicted by the hypothetical natural history. CONCLUSION: A particular form of
      treatment of BPD has relatively long-lasting, beneficial effects.

PMID- 15842032
TI  - Sex reassignment: outcomes and predictors of treatment for adolescent and adult
      transsexuals.
AB  - BACKGROUND: We prospectively studied outcomes of sex reassignment, potential
      differences between subgroups of transsexuals, and predictors of treatment course
      and outcome. METHOD: Altogether 325 consecutive adolescent and adult applicants
      for sex reassignment participated: 222 started hormone treatment, 103 did not;
      188 completed and 34 dropped out of treatment. Only data of the 162 adults were
      used to evaluate treatment. Results between subgroups were compared to determine
      post-operative differences. Adults and adolescents were included to study
      predictors of treatment course and outcome. Results were statistically analysed
      with logistic regression and multiple linear regression analyses. RESULTS: After
      treatment the group was no longer gender dysphoric. The vast majority functioned
      quite well psychologically, socially and sexually. Two non-homosexual male-to
      female transsexuals expressed regrets. Post-operatively, female-to-male and
      homosexual transsexuals functioned better in many respects than male-to-female
      and non-homosexual transsexuals. Eligibility for treatment was largely based upon
      gender dysphoria, psychological stability, and physical appearance. Male-to
      female transsexuals with more psychopathology and cross-gender symptoms in
      childhood, yet less gender dysphoria at application, were more likely to drop out
      prematurely. Non-homosexual applicants with much psychopathology and body
      dissatisfaction reported the worst post-operative outcomes. CONCLUSIONS: The
      results substantiate previous conclusions that sex reassignment is effective.
      Still, clinicians need to be alert for non-homosexual male-to-females with
      unfavourable psychological functioning and physical appearance and inconsistent
      gender dysphoria reports, as these are risk factors for dropping out and poor
      post-operative results. If they are considered eligible, they may require
      additional therapeutic guidance during or even after treatment.

PMID- 15842033
TI  - The relationship between stressful life events, the serotonin transporter (5
      HTTLPR) genotype and major depression.
AB  - BACKGROUND: Serotonin is a good candidate for major depression. We attempted to
      replicate the study by Caspi and colleagues [Science (2003) 301, 386-389] which
      reported a significant interaction between serotonin transporter (5-HTTLPR)
      genotype and stressful life events when predicting major depression. METHOD: We
      typed the serotonin promoter 5-HTTLPR gene in 1206 male and female twins aged 19
      78 years (mean = 39, S.D. = 11). A DSM-IV diagnosis of major depression was
      available for 1199 twins. Most of these twins had participated in a 1988-1990
      study which included a stressful life events inventory and self-report measure of
      depression based on the SCL-90 and DSSI/sAD. Complete 5-HTT genotype and life
      events data, self-report symptoms and major depression diagnoses were available
      for 1091 subjects. We regressed categorical and ordinal measures of depression
      onto stressful life events and genotype. RESULTS: There were significant main
      effects for stressful life events but there was no evidence for any effect of 5
      HTT genotype, nor a genotype x stressful life event interaction. CONCLUSIONS:
      Regardless of whether our results were based on binary logistic or ordinal
      regression analyses we found no evidence to support a main effect of 5-HTTLPR, or
      an interaction between the 5-HTTLPR genotype and stressful life events on major
      depression, Only 20 % of our subjects were aged below 30 years. It is possible
      that the effect reported by Caspi and colleagues is specific to young people, in
      which case our study has much less power in this age group.

PMID- 15842034
TI  - Familial clustering in burnout: a twin-family study.
AB  - BACKGROUND: Research on risk factors for burnout has mainly focused on
      circumstances at work and on personal characteristics. The aim of this study was
      to investigate whether burnout clusters within families and, if so, whether this
      is due to genetic influences or to environmental factors shared by family
      members. Finally, we tried to identify specific risk factors for burnout. METHOD:
      In 2707 twins, 736 of their siblings and 575 of their spouses from a population
      based twin-family sample, burnout was measured using a self-report questionnaire.
      Correlations in burnout scores were obtained for monozygotic and dizygotic twin
      pairs and sibling pairs conditional on the pairs' sex. Correlations for twins and
      their spouses were derived conditional on the length of the relationship.
      RESULTS: In the final model, correlations of the monozygotic and dizygotic twin
      pairs and sibling pairs were significantly different from zero, but not
      significantly different from each other. The correlation was estimated at 0.22.
      The correlation between spouses was also significant. This was mainly due to the
      group with a relationship longer than 5 years in which the correlation was 0.24.
      Burnout scores were higher in subjects whose parents had a high level of
      education. CONCLUSIONS: There is familial clustering for burnout due to
      environmental factors shared by family members, explaining 22 % of the variance.
      Genetic factors do not seem to be of importance. The significant correlation
      between spouses supports the conclusion that common environment plays a role in
      burnout. A high parental education is one of the familial risk factors.

PMID- 15842035
TI  - Formal thought disorder in schizophrenia: an executive or a semantic deficit?
AB  - BACKGROUND: It has been hypothesized that the schizophrenic symptom of formal
      thought disorder is linked to both executive and semantic dysfunction. METHOD:
      Intellectually preserved schizophrenic patients with (n = 15) and without (n =
      16) formal thought disorder, plus matched normal controls (n = 17) were
      administered four executive and four semantic tests. Tests of verbal fluency and
      comprehension of grammar were also given. RESULTS: The patients with formal
      thought disorder were significantly impaired on all four executive tests compared
      to the patients without the symptom. They were only impaired compared to non
      thought-disordered patients on 1 of 4 semantic tests, which probed semantic
      associations between concepts. Naming performance did not distinguish the two
      groups, nor did a previously used measure of semantic fluency controlling for
      phonological fluency. CONCLUSIONS: The results provide support for a dysexecutive
      hypothesis of formal thought disorder in schizophrenia, and, in line with other
      studies, suggest that there may be a restricted 'higher-order' semantic deficit
      which spares naming.

PMID- 15842036
TI  - A model of verbal memory impairments in schizophrenia: two systems and their
      associations with underlying cognitive processes and clinical symptoms.
AB  - BACKGROUND: In a broad cognitive study of schizophrenia we investigated the
      relationships of verbal memory impairments with cognitive underpinnings on the
      one hand, and clinical symptomatology on the other. The results have been
      reported in previous papers. In this paper we show how all these data could be
      integrated into a consistent pattern of associations. METHOD: Fifty schizophrenic
      patients underwent a cognitive battery including a verbal memory task with free
      recall and recognition, a source memory task, and tests of processing speed and
      selective attention. Ratings for positive, negative and depressive symptoms were
      available for 40 of the patients. RESULTS: A factorial analysis revealed a
      distinction between measures of memory efficiency and measures of memory errors.
      The system of memory efficiency was associated with processing speed and
      selective attention at the cognitive level, and with depression at the symptom
      level. The system of memory errors was assumed to be underlain by source
      monitoring deficits. These memory errors were increased by positive symptoms and
      decreased by certain negative symptoms. CONCLUSIONS: All the measures drawn from
      various memory tasks could be integrated into a model describing their
      associations with cognitive underpinnings and clinical symptomatology. This model
      provides a heuristic for the cognitive and pharmacological treatments of verbal
      memory impairments in schizophrenia, as well as for the understanding of positive
      symptoms.

PMID- 15842037
TI  - Exposure therapy and cognitive behaviour therapy.

PMID- 15842038
TI  - Applying CBT to promote recovery from acute psychosis.

PMID- 15842039
TI  - Platelet aggregation testing in platelet-rich plasma: description of procedures
      with the aim to develop standards in the field.
AB  - Platelet function testing consisting of platelet aggregation and secretion often
      is requested in the clinical evaluation of patients with bleeding problems. At
      present, there are no uniform clinical laboratory standards for the performance
      or interpretation of these studies. The present report describes one laboratory's
      methods and interpretations of platelet aggregation and secretion studies of
      platelet-rich plasma using each of the common platelet agonists. Diagnostic
      categories for the evaluation of the platelet function testing are presented. The
      diagnostic categories then are applied to the evaluation of 61 patients referred
      to our medical center for these studies. The aims of this report are to present
      clinical platelet aggregation and secretion studies and to provide a working
      schema to evaluate these results. Our intent is to stimulate interest in the
      development of professional guidelines for platelet function testing in the
      clinical laboratory.

PMID- 15842040
TI  - Clinical impact of point-of-care vs laboratory measurement of anticoagulation.
AB  - Patients using anticoagulation point-of-care (POC) monitors are advised to
      periodically test these systems against laboratory methods to monitor
      performance. The international normalized ratio (INR), however, can vary between
      test systems owing to different instrument-reagent combinations. In a randomized
      study evaluating warfarin self-management, we compared INR measured by patients
      on a POC monitor (ProTime, International Technidyne Corporation, Edison, NJ) with
      those obtained at a hospital laboratory within 1 hour Ninety-one paired INR
      determinations from 55 patients met inclusion criteria. Clinical agreement in
      which POC and laboratory INR were within or outside the target INR range occurred
      in 56 (62%) of 91 cases (kappa = 0.35). The mean (SD) difference between POC and
      laboratory INR was 0.44 (0.61). Six pairs differed by 1 or more INR units, 3 at
      study initiation resulting in POC monitor replacement. The accuracy of INR self
      testing with ProTime was acceptable. The small failure rate of INR agreement
      might be clinically important, suggesting the need for external quality control
      systems.

PMID- 15842041
TI  - External quality assurance of DNA testing for thrombophilia mutations.
AB  - Because of the potential implications of results of genetic analyses of
      thrombophilic mutations, laboratories must undertake stringent internal quality
      control measures and participate in external quality assurance (QA) programs. A
      small number of external QA surveys of thrombophilic defects have been conducted
      across a large number of molecular laboratories and generally have indicated
      favorable levels of correct responses. The Royal College of Pathologists of
      Australasia QA program has conducted external QA testing of factor V Leiden G1691
      A, prothrombin G20210A, and MTHFR C677T gene mutations for the past 5 years,
      including 133 DNA samples in 10 multilaboratory surveys. Of 3,799 responses, the
      overall success rate was 98.63%; the poorest individual sample result was 15%
      incorrect for a homozygous factor V Leiden sample. Success rates in identifying
      specific mutations were 98.13% for factor V Leiden, 98.84% for prothrombin
      G20210A, and 99.3% for the MTHFR C677T mutation. Among responding laboratories,
      51% (20/39) made at least 1 error; 3 of 39 laboratories were responsible for 46%
      of all errors (24/52). Although encouraging, these data underscore the need for
      ongoing participation of molecular diagnostic laboratories in external QA
      programs to ensure the provision of quality genetic testing services.

PMID- 15842042
TI  - T-cell large granular lymphocytic leukemia of donor origin occurring after
      allogeneic bone marrow transplantation for B-cell lymphoproliferative disorders.
AB  - T-cell lymphoproliferative disorders are uncommon occurrences after bone marrow
      transplantation (BMT). We describe 2 patients in whom a monoclonal T-cell large
      granular lymphocytosis (T-LGL) developed after allogeneic BMT for B-cell
      lymphoproliferative disorders. Both patients showed a persistent expansion of
      CD3+, CD8+, and CD57+ large granular lymphocytes of donor origin with clonally
      rearranged T-cell receptor gamma genes and no evidence of Epstein-Barr virus
      related infection. The manifestations were consistent with T-LGL leukemia as
      defined by the World Health Organization criteria. In both patients, graft-vs
      host disease developed, and 1 had recurrent episodes of cytomegalovirus viremia.
      The other patient had received a graft from a hepatitis C antibody-positive donor
      without developing any signs of hepatitis C infection. Both patients remain in
      complete remission from their B-cell lymphoproliferative disorders and do not
      have symptoms related to T-LGL leukemia. These data show that T-LGL leukemia
      should be included as one of the types of posttransplantation lymphoproliferative
      disorders that can occur after allogeneic BMT for B-cell neoplasms.

PMID- 15842043
TI  - Lymphoid neoplasms associated with IgM paraprotein: a study of 382 patients.
AB  - We identified 382 consecutive patients with lymphoid neoplasms associated with
      serum monoclonal IgM paraprotein and classified each neoplasm according to World
      Health Organization criteria. Lymphoplasmacytic lymphoma/Waldenstrom
      macroglobulinemia (LPL/WM) was most common, 225 cases (median serum IgM level,
      2.2 g/dL; range, 0.2-10.9 g/dL). For 157 cases, classification and median (and
      range in g/dL) IgM levels were as follows: chronic lymphocytic leukemia/small
      lymphocytic lymphoma (CLL/SLL; n = 77), 0.9 (0.1-2.1); marginal zone lymphoma (n
      = 27), 0.5 (0.1-2.4); follicular lymphoma (n = 18), 0.4 (0.1-1.6); mantle cell
      lymphoma (n = 11), 0.4 (0.2-1.3); diffuse large B-cell lymphoma (DLBCL; n = 7),
      0.5 (0.2-1.0); DLBCL associated with low-grade lymphoma (n = 5), 0.9 (0.4-3.0);
      angioimmunoblastic T-cell lymphoma (n = 4), 0.8 (0.8); and CD5+CD23- low-grade B
      cell lymphoma, unclassified (n = 8), 0.5 (0.3-2.9). The results show IgM
      paraproteinemia was associated most commonly with LPL/WM (58.9%), followed by
      CLL/SLL (20.2%). Although serum IgM levels greater than 3 g/dL were restricted to
      patients with LPL/WM, most patients with LPL/WM had paraprotein levels less than
      3 g/dL. Thus, serum IgM paraprotein level is not a reliable discriminator in
      differential diagnosis.

PMID- 15842044
TI  - Analytic performance of the PENTRA 80 automated blood cell analyzer for the
      evaluation of normal and pathologic WBCs.
AB  - We evaluated performance of the ABX PENTRA 80 (ABX Diagnostics, Montpellier,
      France) hematology analyzer in enumerating the most frequent subsets of WBCs in
      peripheral blood, atypical lymphocytes (ALYs), and large immature cells (LICs) by
      comparing results with those obtained by manual microscopic counts, another
      hematology analyzer, and flow cytometric immunophenotyping. Identification and
      enumeration of neutrophils and lymphocytes with the PENTRA 80 showed high
      correlation with all 3 reference methods (R2 > or = 0.92 and R2 > or = 0.88,
      respectively); quantification of eosinophils showed good correlation with the
      other analyzer and flow cytometric immunophenotyping (R2 > or = 0.70); lower
      correlation coefficients were found for comparisons with conventional microscopy
      (R2 > or = 0.50). For monocytes, lower but acceptable correlation and agreement
      were found; marginal correlation was found for basophils. The PENTRA 80 also
      showed good performance in detecting LICs but was less effective for the
      identification of ALYs in relatively low frequencies in abnormal peripheral blood
      samples. We found good performance of the 5-part leukocyte differential analyses
      for the PENTRA 80, especially for enumeration of neutrophils, lymphocytes,
      eosinophils, and LICs.

PMID- 15842045
TI  - Composite B-cell and T-cell non-Hodgkin lymphoma of the tibia.
AB  - We report a unique case of de novo composite lymphoma in the tibia of a 35-year
      old man who presented with increasingly frequent and intense pain in the right
      upper leg. He was otherwise healthy without significant medical history. A plain
      radiograph of the right leg showed a permeative lesion with alternating areas of
      radiolucency and radiodensity in the upper third of the tibia. Magnetic resonance
      imaging showed a large, heterogeneous enhancing lesion involving the medullary
      and cortical bone of the proximal tibia with cortical disruption and extension
      into the adjacent soft tissue. A biopsy showed sheets and clusters of large
      cells, punctuated by clusters of small, irregular lymphocytes. Flow cytometry and
      immunohistochemical analysis showed composite lymphoma: diffuse large B-cell
      lymphoma (DLBCL) and peripheral T-cell non-Hodgkin lymphoma with predominantly
      small cell morphologic features. The DLBCL expressed CD19, CD20, CD79a, CD5,
      CD10, CD23, CD38, CD117, bcl-2, and bcl-6, with monotypic expression of
      immunoglobulin kappa light chain. The T cells expressed CD2, CD3, CD5, CD7, and
      CD8, with partial loss of CD4. Clonal rearrangement of T-cell receptor gamma
      chain gene was found. Neither the large B cells nor the small T cells expressed
      Epstein-Barr virus-encoded RNA. Physical examination and radiologic studies
      showed no evidence of lymphadenopathy, organomegaly, or other mass lesions in the
      body. No peripheral lymphocytosis or bone marrow involvement was present.

PMID- 15842046
TI  - EBV-associated B- and T-cell posttransplant lymphoproliferative disorders
      following primary EBV infection in a kidney transplant recipient.
AB  - Posttransplant lymphoproliferative disorders (PTLDs) usually are of B-cell
      lineage and associated with Epstein-Barr virus (EBV). PTLDs of T-cell lineage are
      much less common and infrequently associated with EBV. We report a rare case of a
      girl in whom B-cell and T-cell PTLDs developed following 2 EBV-negative kidney
      transplants. Within 2 years of the second transplantation, the originally EBV
      negative patient developed both an EBV-associated clonal B-cell PTLD involving
      lymph nodes and an EBV-positive T-cell PTLD involving bone marrow and liver.
      These proliferations occurred concurrently with evidence of primary EBV infection
      and high plasma viral load. The patient eventually died of multiorgan failure 5
      years after the initial transplant (3 years after the second transplant). To our
      knowledge, only 4 cases of both B-cell and T-cell PTLDs have been reported. Only
      2 cases have been proven to be monoclonal and EBV-associated, as in this case,
      the first following kidney transplantation.

PMID- 15842047
TI  - Using an AMACR (P504S)/34betaE12/p63 cocktail for the detection of small focal
      prostate carcinoma in needle biopsy specimens.
AB  - We assessed the usefulness of immunohistochemical analysis with a 3-antibody
      cocktail (alpha-methylacyl coenzyme A racemase [AMACR, or P504S], 34betaE12, p63)
      and a double-chromogen reaction for detection of limited prostate cancer in 138
      needle biopsy specimens, including 82 with small foci of prostatic adenocarcinoma
      and 56 benign prostates. When carcinoma was present, red cytoplasmic granular
      staining (AMACR) in the malignant glands and cells and dark brown nuclear (p63)
      and cytoplasmic (34betaE12) staining in basal cells of adjacent nonmalignant
      glands were found. Of 82 cases of small foci of prostatic adenocarcinoma, 78
      (95%) expressed AMACR; all malignant glands were negative for basal cell
      staining. All benign glands adjacent to malignant glands were recognized easily
      by basal cell marker positivity and little or no AMACR expression. No benign
      glands were simultaneously positive for AMACR and negative for basal cell markers
      (specificity, 100%). There were no differences in intensity and numbers of
      positive glands with double-chromogen staining compared with using 1-color
      staining. Our results indicate that immunohistochemistry with a 3-antibody
      cocktail and double chromogen is a simple and easy assay that can be used as a
      routine test, which overcomes the problems of studying small lesions in prostate
      needle biopsies with multiple immunohistochemical stains.

PMID- 15842048
TI  - Chromogenic in situ hybridization for the detection of HER-2/neu gene
      amplification in breast cancer with an emphasis on tumors with borderline and low
      level amplification: does it measure up to fluorescence in situ hybridization?
AB  - We compared chromogenic in situ hybridization (CISH) with fluorescence in situ
      hybridization (FISH) for assessing HER-2/neu gene amplification using tissue
      microarrays (TMAs) made from formalin-fixed, paraffin-embedded tissue blocks from
      113 cases of invasive breast carcinoma. TMAs were created using 0.6-mm tissue
      cores with 4 sampled cores per tumor. For both assays, a HER-2/chromosome 17
      signal ratio of 2.0 or more was considered positive for gene amplification. The
      average ratio of cores from the same tumor was used for determination of gene
      amplification status of that particular tumor Of 113 cases, 102 were tested
      successfully by both assays. The results were concordant in 100.0% of cases (63
      amplified; 39 nonamplified). All 22 cases of borderline (ratio, 2.0-2.5) or low
      level (ratio, 2.6-3.9) amplification by FISH also showed HER-2 gene amplification
      by CISH. CISH is as sensitive as FISH in detecting borderline and low-level HER-2
      amplification. Reliable recognition of the invasive carcinoma area by light
      microscopy and preservation of the test slides are added advantages of CISH. CISH
      performs as well as FISH in the analysis of HER-2 gene amplification in breast
      cancer and might have advantages in certain situations.

PMID- 15842049
TI  - Is cytomegalovirus associated with human colorectal tumorigenesis?
AB  - Despite the rapid advance in the understanding of molecular pathways underlying
      human colorectal tumorigenesis, the causes that initiate dysregulation of the
      pathways remain largely unknown. Human cytomegalovirus (CMV) has been implicated
      as a potential etiopathogenetic agent. To further investigate whether CMV
      participates in human colorectal tumorigenesis, we examined 23 colorectal
      hyperplastic polyps, 65 colorectal adenomas, and 51 colorectal adenocarcinomas by
      immunohistochemical analysis using 2 antibody mixtures that recognize CMV
      immediate early, early, and delayed gene products. The results show that while
      typical nuclear staining (with or without cytoplasmic positivity) was observed in
      control cases of CMV colitis, no nuclear positivity was detected in any cases
      studied. Focal and weak cytoplasmic staining was noted in a subset of cases,
      particularly when a higher antibody concentration was used. This staining was
      believed to be nonspecific, however, because it also was observed in normal
      appearing colonic mucosa. In addition, polymerase chain reaction failed to detect
      the presence of CMV DNA in 24 selected cases showing nonspecific cytoplasmic
      immunostaining. These observations demonstrate an absence of CMV proteins and DNA
      in human colorectal adenocarcinomas and their precursor lesions.

PMID- 15842050
TI  - A novel filtration-based processing method of liquid cytology specimens for human
      papillomavirus DNA testing by hybrid capture II.
AB  - We evaluated a more efficient method of processing liquid-based cervical cytology
      specimens for human papillomavirus (HPV) DNA testing by Hybrid Capture II (HCII).
      Aliquots were made from 701 specimens in the following sequence: 4.0, 2.0, 1.0,
      0.5, and 1.5 mL. The 4.0-mL aliquot was processed by the standard method (STP),
      and half of the processed material was tested by HCII. Other aliquots were
      processed with a new, filtration-based processing method (NPM). The 2.0-mL NPM
      aliquot had HCII test performance most similar to the STP, ie, similar HCII
      positivity (P = .4) and good test agreement (kappa = 0.85, 95% confidence
      interval [CI], 0.80-0.89). The 194 cytologic negatives had greater positivity by
      STP (P = .04) compared with the 2.0-mL aliquot processed by NPM; between-method
      agreement was modest (kappa = 0.54, 95% CI, 0.36-0.72). A lower positive cut
      point for the 2.0-mL NPM aliquot partially abrogated this minor difference. In
      241 specimens diagnosed as low-grade and 31 as high-grade squamous
      intraepithelial lesions, there were no significant differences in HPVpositivity
      (>85% and 90%, respectively) between STP and NPM. NPM reduces specimen handling
      and decreases total testing time by approximately 33% without significant losses
      in HCII test performance.

PMID- 15842051
TI  - BRAF gene mutations are rare events in gastroenteropancreatic neuroendocrine
      tumors.
AB  - The BRAF gene, one of the human isoforms of RAF, is activated by ras, leading to
      cooperative effects in cells responsive to growth factor signals. We studied the
      frequency of BRAF and k-ras-2 mutations in primary neuroendocrine
      gastroenteropancreatic (GEP) tumors. Mutation analysis of the BRAF and k-ras-2
      genes was performed in 40 primary neuroendocrine tumors of the GEP system. The
      expression of extracellular signaling-related kinase (ERK) 1/2, an important
      downstream point of convergence in the ras-RAF-mitogen-activated protein-ERK
      pathway was analyzed immunohistochemically. We detected one 1796 T-->A BRAF
      mutation that led to a substitution of valine by glutamic acid at position 599
      (V599E) in 40 primary neuroendocrine GEP tumors (3%). We failed to detect
      specific mutation of the k-ras-2 gene. We identified constitutively activated ERK
      in almost all neuroendocrine tumor tissues tested irrespective of BRAF mutation
      or localization or functional activity. These results suggest that BRAF mutations
      do not have a role in tumorigenesis of neuroendocrine tumors. Nevertheless,
      activation of the RAF/mitogen-activated protein kinase pathway might have a
      causative role in the development of neuroendocrine tumors, independent of BRAF
      or k-ras-2 mutation.

PMID- 15842052
TI  - High prevalence of herpes simplex virus DNA in temporal arteritis biopsy
      specimens.
AB  - Giant cell arteritis (GCA) affecting the cranial arteries is a disease of unknown
      cause that causes blindness, stroke, and other morbidity. Its sudden onset and
      segmental distribution are suggestive of diseases that involve viral
      reactivation, and cranial arteries are known to be innervated by ganglia that
      harbor herpes simplex virus (HSV). We used a high-sensitivity polymerase chain
      reaction assay to test for HSV DNA in specimens from 39 consecutive temporal
      artery biopsies performed for suspected GCA. HSV DNA was detected in 21 (88%) of
      24 histologically positive and 8 (53%) of 15 histologically negative specimens (P
      = .027; Fisher exact test). Analysis of 10 renal artery samples from age-matched
      control subjects using the same assay showed no detectable HSV DNA. We conclude
      that detectable HSV DNA is correlated with histologically confirmed GCA in this
      patient population.

PMID- 15842053
TI  - Pulmonary metastasis from liposarcoma: a clinicopathologic and
      immunohistochemical study of 24 cases.
AB  - A review of the histologic features of pulmonary metastasis and clinical
      implications of liposarcoma (LS) is given for 24 cases (8 each) of the 3 types of
      LS: myxoid LS (ML), pleomorphic LS (PL), and dedifferentiated LS (DDL). Most
      patients were men. Metastatic ML and PL were distributed almost equally among the
      lung lobes, whereas DDL was more common in the left lower lobe. The metastatic
      MLs had variable cellularity ranging from singly scattered cells in a hyalinized
      stroma (treatment-related effect) to hypercellular ML. Most PLs (6/8) were
      nonlipogenic and resembled an undifferentiated pleomorphic sarcoma. All
      metastatic DDLs had high-grade histologic features and were predictably
      nonlipogenic. After pulmonary metastasectomy, 2 patients with ML and 1 with PL
      were disease-free. The other 6 patients with ML, 7 with PL, and all with DDL had
      progressive disease. The morphologic features of LS metastatic to the lungs seem
      diverse but within the spectrum of the histologic type expected from the primary
      tumor. Overall, the general trend for these LS subsets is progressive disease,
      metastatic disease for ML and PL with a much shorter interval for PL, and
      metastatic disease and local recurrence for DDL.

PMID- 15842054
TI  - 1D5 and 6F11: An immunohistochemical comparison of two monoclonal antibodies for
      the evaluation of estrogen receptor status in primary breast carcinoma.
AB  - The optimal monoclonal antibody to examine steroid hormone receptor status of
      primary breast carcinoma has yet to be defined. Estrogen receptor status was
      evaluated in 592 cases using routinely prepared paraffin-embedded tissue samples
      from primary breast carcinomas with the 1D5 (DAKO, Carpinteria, CA) and 6F11
      (Novocastra, Newcastle upon Tyne, England) monoclonal antibodies. The stains were
      compared, assessing the percentage of positive cells stained and their intensity.
      They also were examined for nonspecific cytoplasmic staining and fixation
      artifact. In addition, a cost analysis for their production was performed.
      Overall, 1D5 and 6F11 showed a 97.5% concordance rate. 6F11 stained a
      significantly higher percentage of cells (P < .0001), more intensely (P < .0001),
      with less nonspecific cytoplasmic staining (P < .0001). There was no significant
      difference in fixation artifact between the 2 clones. The cost of antibody used
      for preparing a 1D5-stained slide was 86% more than for preparing a 6F11-stained
      slide (dollars 14.27 vs dollars 7.67).

PMID- 15842055
TI  - Assisted primary screening using the automated ThinPrep Imaging System.
AB  - We report the clinical trial studies for the ThinPrep Imaging System (TIS; Cytyc,
      Boxborough, MA). Between December 2000 and July 2001, 10,742 ThinPrep specimens
      were collected at 4 US clinical sites representative of the normal clinical
      population of the laboratories, including screening patients and referred
      patients. After nonstudy screening diagnoses were completed, the vials were
      relabeled and randomized, and study slides were prepared and stained. TIS-trained
      cytotechnologists and pathologists screened the slides twice, first manually,
      then TIS-assisted after an appropriate interval. Afterward, 3 independent
      pathologists performed an adjudication study to determine definitive diagnoses
      for the nonnegative slides and 5% of the negative slides; the adjudicated
      diagnoses served as the "gold standard" for subsequent sensitivity and
      specificity analyses. TIS-assisted screening was statistically more sensitive
      than manual screening for atypical squamous cells of undetermined significance
      (ASCUS) or higher (+) and statistically equivalent for low- (LSIL)+ and high
      grade squamous intraepithelial lesion (HSIL)+ diagnoses. TIS-assisted screening
      had equivalent specificity for ASCUS+ and LSIL+ and significantly higher
      specificity for HSIL+. Average cytologists' daily screening rates doubled with
      TIS-assisted screening. The sensitivity of the TIS-assisted screening system
      equals or exceeds the sensitivity of manual primary screening without adversely
      affecting specificity, and TIS-assisted screening can improve cervical cancer
      screening productivity. Cost issues require further study.

PMID- 15842056
TI  - Analytic performance of the iQ200 automated urine microscopy analyzer and
      comparison with manual counts using Fuchs-Rosenthal cell chambers.
AB  - Automated instruments that can examine urine for cells and particles have reduced
      the need for labor-intensive manual microscopy. We evaluated the performance of
      the Iris iQ200 Automated Urine Microscopy Analyzer (Iris Diagnostics, Chatsworth,
      CA) and compared results with manual cell and particle counts using Fuchs
      Rosenthal counting chambers. Within-run imprecision (coefficient of variation) of
      the iQ200 for urine samples ranged from 3.0% to 45% for RBC counts between 1,029
      and 3 x 10(6) cells/L, 3.4% to 40% for WBC counts between 1,006 and 4 x 10(6)
      cells/L, and 8.9% to 35% for epithelial cell counts between 93 and 4 x 10(6)
      cells/L. Between-run imprecision was 3.3% at 1,017 x 10(6) cells/L and 19.2% at
      28 x 10(6) cells/L. There was good agreement between the iQ200 and manual cell
      counts (r > or = 0.94); however; the iQ200 produced lower results based on slopes
      of 0.92 (RBC count), 0.81 (WBC count), and 0.94 (epithelial cell counts). The
      iQ200 has satisfactory performance and correlates well with manual cell counts.
      Most urine samples containing RBCs, WBCs, and epithelial cells can be reported
      without review of captured images.

PMID- 15842057
TI  - Elevation of plasma and cerebrospinal fluid osteopontin levels in patients with
      atypical teratoid/rhabdoid tumor.
AB  - Osteopontin, a cancer metastasis-associated gene, is specifically up-regulated in
      central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT), but its
      biological behavior in the progression of CNS AT/RT has never been studied. We
      obtained plasma, cerebrospinal fluid (CSF), and brain tissue specimens from
      lobectomy or hemispherectomy samples from 39 patients (medulloblastoma, 16;
      AT/RT, 8; epilepsy, 6; hydrocephalus, 9). By enzyme-linked immunosorbent assay,
      the median osteopontin levels in plasma and CSF in AT/RT (852.0 and 1,175.0
      ng/mL, respectively) were significantly higher than in medulloblastoma (492.5 and
      524.5 ng/mL, respectively) and hydrocephalus and epilepsy (208.0 and 168.0 ng/mL,
      respectively) (P < .05). The results of real-time reverse transcriptase
      polymerase chain reaction and immunohistochemical analysis demonstrated that
      osteopontin expression in AT/RT (n = 5) was significantly higher than in
      medulloblastoma (n = 8) samples. The differences in osteopontin expression in
      plasma, CSF, and tumor samples in AT/RT and medulloblastoma correlated with
      survival differences. In 5 patients with AT/RT, plasma osteopontin levels
      decreased after treatment but increased with relapse. Osteopontin might be a
      potential marker to aid in identifying AT/RT recurrence.

PMID- 15842058
TI  - Innate immunity: New approaches to understanding its clinical significance.
AB  - Immunologists view innate immunity as evolution's ancient host response to
      infectious agents. Unlike vertebrates, in which antibodies and T-cell subsets
      rely on somatic mutations, molecular participants of innate immunity are encoded
      in the genome. Despite its heritage, many of innate immunity's sentinel
      molecules, intracellular transcriptional controls, and effector molecules
      participate in the pathogenesis of numerous complex human diseases. Toll-like
      receptors (TLRs), an important starting point, contact the environment and
      provide specific sensing for an important component of innate immunity. TLRs,
      found on macrophages, dendritic cells, and endothelial cells, recognize specific
      microbial molecular patterns. Beginning with these sentinel molecules, the
      process leads through intracytoplasmic mediators of transcription control and
      culminates with an array of host immune responses. Effector molecules include
      cytokines and the complement system. Polymorphisms within TLR genes might
      contribute to the pathogenesis of complex diseases. Disease associations linked
      to single nucleotide polymorphisms are in the early stage of experimental
      discovery; important clinical insights are emerging. Along these lines, studies
      of asthma provide an excellent example of how ancient ligand-receptor
      interactions and TLR polymorphisms provide new understanding of a common disease.
      New knowledge could facilitate the development of novel therapies.

PMID- 15842059
TI  - Cell line standards to reduce HER-2/neu assay variation and the potential of
      automated image analysis to provide more accurate cut points for predicting
      clinical response to trastuzumab.

PMID- 15842060
TI  - Diagnosis and treatment of dermatitis due to formaldehyde resins in clothing.
AB  - An increasing number of cases of allergic contact dermatitis secondary to
      formaldehyde resins used for textile finishes have been seen in our office over
      the last several years. Although previously reported to be more common in women,
      we have seen almost as many men as we have seen women with this condition,
      possibly because men are more likely to be occupationally sensitized to
      formaldehyde. We have found that patch-test reactions of only questionable
      strength may be clinically relevant. It has been our experience that many of
      these cases are of long duration before referral for patch testing. A low index
      of suspicion leads to a delayed diagnosis, and avoidance after diagnosis is
      difficult owing to the lack of labeling requirements for textile finishes. Patch
      testing with the textile resins Fixapret AC and Fixapret CPN most often
      identified patients with textile allergies. We have prepared a handout to give
      patients more definitive recommendations.

PMID- 15842061
TI  - North American Contact Dermatitis Group patch-test results, 2001-2002 study
      period.
AB  - BACKGROUND: Allergic contact dermatitis is a significant cause of cutaneous
      disease affecting many individuals in the home and at the workplace. Patch
      testing is the most worthwhile diagnostic tool for the evaluation of patients
      with suspected allergic contact dermatitis. OBJECTIVE: This study reports the
      results of patch testing from January 1, 2001, to December 31, 2002, by the North
      American Contact Dermatitis Group (NACDG). METHODS: Patients were tested with an
      extended screening series of 65 allergens. A standardized patch-testing technique
      was used. Data from these patients were recorded on a standardized computer entry
      form and analyzed. RESULTS: Sixty-five allergens were tested on 4,913 patients.
      The top 10 allergens remain the same in this study period as in the 1999-2000
      study period: nickel sulfate (16.7%), neomycin (11.6%), Myroxilon pereirae
      (balsam of Peru) (11.6%), fragrance mix (10.4%), thimerosal (10.2%), sodium gold
      thiosulfate (10.2%), quaternium-15 (9.3%), formaldehyde (8.4%), bacitracin
      (7.9%), and cobalt chloride (7.4%). Of the 4,913 patients tested, 69% had at
      least one positive allergic patch-test reaction. Of all patients, 15.8% had
      occupation-related dermatitis; 15.4% were determined to have irritant contact
      dermatitis, and 11.1% of the 15.4% had a relevant reaction to an occupational
      irritant. Of all patients tested, 16.7% had a relevant reaction to an allergen
      not in the NACDG standard series, and 5.5% had a relevant reaction to an
      occupational allergen not in the standard series. CONCLUSION: Our findings once
      again reinforce the need for a more comprehensive group of diagnostic allergens
      than those found in the standard screening kits. The usefulness of patch testing
      is enhanced when a greater number of allergens are tested, especially nonstandard
      allergens occupationally encountered.

PMID- 15842062
TI  - Optimizing skin protection with semipermeable gloves.
AB  - BACKGROUND: Occlusion due to gloves is one important cause of glove irritation.
      Macerated softened skin gives poor protection against microbes and chemical
      injuries. The introduction of a breathable protective glove material would
      represent a significant step toward improved prevention of occupational skin
      disease. OBJECTIVE: Performance levels of semipermeable and occlusive gloves were
      examined under conditions typical of the hairdressing profession. In two studies,
      tests comparing breathable semipermeable gloves to single-use gloves made of
      occlusive materials were conducted. METHODS: In an initial study, a user survey
      was carried out in conjunction with bioengineering examinations. Values at
      baseline and values after gloves were worn were recorded by measuring
      transepidermal water loss (TEWL), skin humidity (SH), and skin surface hydrogen
      ion concentration (pH) in 20 healthy volunteers. In a second study, the gloves
      were tested for penetrability and permeability with three chemical compounds
      typically used in the hairdressing profession. RESULTS: Bioengineering
      examination objectively confirmed users' reports of reduced hand perspiration
      when semipermeable gloves were worn. The TEWL, SH, and skin surface pH values
      remained largely stable after 20 minutes of wearing semipermeable gloves, in
      contrast to the reactions observed with gloves of occlusive materials.
      Permeability tests indicated that the semipermeable material is effective, with
      some restrictions. Air leakage testing revealed that all 50 gloves tested were
      not airtight. CONCLUSION: Following the optimization of manufacturing methods,
      additional tests of the penetrability of semipermeable gloves will be necessary.

PMID- 15842063
TI  - Clinical presentations of patients sensitive to natural rubber latex.
AB  - BACKGROUND: Eczematous reactions to natural rubber latex (NRL) have been
      associated with both immediate and delayed hypersensitivity. OBJECTIVE: To
      determine clinical cases that might require testing for immediate sensitivity or
      patch testing for delayed hypersensitivity to latex fabric. METHODS: Patients
      with suspected sensitivity to NRL were given in vitro testing by
      radioallergosorbent test (RAST) or ImmunoCAP test and if negative, were prick
      tested. If prick-test results were negative and the patients were still
      available, patch testing was done with latex glove fabric. Case histories of
      persons with positive results on RASTs, ImmunoCAP tests, prick tests, and patch
      tests were reviewed for clinical presentation and relevance. RESULTS: Of 92
      persons with positive responses, 26 had positive RAST results, 26 had positive
      ImmunoCAP test results, 33 had positive prick-test results, and 7 had a positive
      patch-test result. Presentations included hand urticaria or eczema (46 patients),
      eyelid dermatitis (14), shoe dermatitis (10), atopic eczema (6), waistband
      dermatitis (5), clothing dermatitis (3), contact eczema to elastic in a mask (2),
      urticaria to a phlebotomy tourniquet, and eczema over the elbows and from an
      elastic bandage used for occlusive dressing therapy. Several other presentations
      were less likely to be relevant. CONCLUSION: Persons with putative contact
      dermatitis in areas that may come into contact with NRL deserve not only to be
      patch-tested with rubber chemicals but also to be tested for immediate
      sensitivity and, if results are negative, to be patch-tested with NRL.

PMID- 15842064
TI  - Occupational allergic contact dermatitis from antioxidant amines in a dental
      technician.
AB  - We describe an 18-year-old dental technician who presented with dry
      hyperkeratotic lesions on his left palm that were limited to an area that was in
      contact with a container in which he had prepared the molds for a dental
      prosthesis. On patch testing, he had a positive reaction to black rubber mix and
      its components N-cyclohexyl-N'-phenyl-4-phenylenediamine, N,N'-diphenyl-4
      phenylenediamine, and N-isopropyl-N'-phenyl-4-phenylenediamine, as well as to a
      piece of the rubber container. Thin-layer chromatography (TLC) of a piece of the
      rubber container confirmed the presence of the para-phenylenediamine mix. Results
      of patch-testing with TLC were positive after 48 and 96 hours. The lesions
      resolved when the patient stopped using the container. The patient was diagnosed
      with occupational allergic contact dermatitis. We also review the dermatoses
      caused by antioxidant amines.

PMID- 15842065
TI  - Occupational contact allergy and dermatitis from methylisothiazolinone after
      contact with wallcovering glue and after a chemical burn from a biocide.
AB  - Skin exposure to biocides containing high concentrations of
      methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) may cause severe
      chemical burns and may also induce sensitization. We report two cases in which
      skin exposure to a newly launched biocide containing 2-methyl-4-isothiazolin-3
      one (MI) and 1,2-benzisothiazolin-3-one led to sensitization to Ml, which in the
      second case was preceded by a chemical burn. A study was performed to investigate
      the pattern of reactivity to MCI and Ml in two patients who presumably had a
      primary sensitization to Ml and in one patient who had been sensitized to MCI/MI
      by being patch-tested. The patients were patch-tested with serial dilutions of
      MCI/MI, MCI, MI, and 2-n-octyl-4-isothiazolin-3-one. The first two patients
      reacted to both MCI/MI and the separate active ingredients, with a higher level
      of reactivity to Ml than to MCI. The third patient reacted to MCI/MI and MCI
      only. A biocide containing Ml caused sensitization and occupational contact
      dermatitis in the first two patients, through contact with wallpaper glue in one
      case and after a chemical burn in the other case.

PMID- 15842066
TI  - Neoprene.
AB  - Neoprene is a synthetic rubber with many common uses, including use in shoe
      insoles and adhesives, orthopedic braces, and gloves. Many cases of type IV
      hypersensitivity from neoprene contact have been reported. Thioureas, the most
      commonly used vulcanization accelerators in the manufacture of neoprene, are
      responsible for the majority of these cases. However, thioureas are not included
      in the TRUE Test whereas the North American Contact Dermatitis Group standard
      tray contains only mixed dialkyl thioureas. Since most data indicate that many
      cases will be missed when only mixed dialkyl thioureas are used for screening, a
      more complete thiourea panel should be used when neoprene hypersensitivity is
      suspected.

PMID- 15842067
TI  - Orthopedic prostheses: is there any point in patch testing?
AB  - The aging of our population and the availability of new medical technologies have
      contributed to tremendous growth in the number of patients with implanted
      orthopedic and other devices. As experts on contact dermatitis, we are
      periodically asked to evaluate patients who have a history of metal allergy prior
      to surgery. We are sometimes faced with patients who have experienced
      complications after implant surgery or (more rarely) who have developed skin
      disease temporally related to surgery. To address these controversial issues, we
      asked three experts to discuss the role of patch testing in regard to patients
      with orthopedic implants. Mark D.P. Davis, MD, is an Associate Professor in the
      Department of Dermatology, Mayo Clinic, Rochester, MN; Christen M. Mowad, MD, is
      Assistant Professor of Dermatology, Geisinger Medical Center, Danville, PA; and
      Pamela Scheinman, MD, is Director of the Contact Dermatitis and Occupational
      Dermatology Unit and Assistant Professor of Dermatology, Tufts-New England
      Medical Center, Boston, MA.

PMID- 15842068
TI  - Evaluation of the main contact allergens in oxidized tea tree oil.

PMID- 15842069
TI  - Occupational dermatitis in a milk industry worker due to Kathon CG.

PMID- 15842070
TI  - Preservation of episodic visual recognition memory in aging.
AB  - Visual episodic recognition memory was assessed in young (mean age 22.5 years)
      and older (mean age 74.1 years) adults. To isolate purely visual memory,
      recognition was tested with sets of briefly-presented compound sinusoidal
      gratings, which minimized age-related differences in visual processing, and
      resisted verbal encoding. Recognition was measured after delays of 1, 2 or 4
      seconds. Overall, neither accuracy of recognition nor speed of response differed
      significantly between groups, or with probe delay, which strengthens recent
      claims that visual memory tends to be spared during the course of normal aging.

PMID- 15842071
TI  - Stimulus contrast and word reading speed in Alzheimer's disease.
AB  - The oral word reading speed of patients with Alzheimer's disease (AD) and healthy
      young and older control participants was evaluated across a broad range of
      stimulus contrast levels in two experiments. The impact of stimulus repetition on
      reading speed also was examined. It was found that the older adult participants,
      and particularly the AD patients, were more sensitive to contrast reductions.
      Each subject group was able to read repeated words more rapidly than novel words
      but this repetition effect emerged only at lower stimulus contrast levels. It was
      concluded that AD patients have feature extraction speeds comparable to non
      demented older adults but only when the stimuli are presented at a relatively
      high contrast. These findings suggest that the automatic encoding processes
      involved in word recognition remain intact in mildly demented AD patients given
      stimuli of sufficient strength.

PMID- 15842072
TI  - Association between change in systolic blood pressure and cognitive decline among
      elderly Mexican Americans: data from the Hispanic established population for
      epidemiology study of the elderly.
AB  - The longitudinal association between the rate of change in blood pressure and
      cognitive decline was examined in an area probability sample from a population
      based survey of elderly Mexican Americans, 65 years of age or older obtained in
      1993--1994, 1995--1996, 1998--1999, and 2000--2001 (n = 2859). The sample was
      divided into two groups at baseline: hypertensives had a systolic blood pressure
      (SBP) > or = 140 mm Hg, a diastolic blood pressure (DBP) > or = 90 mm Hg, or
      indicated a prior diagnosis of hypertension, and the normotensive group.
      Cognition was indexed by the Mini-Mental State Examination (MMSE). Neither SBP
      nor DBP at baseline predicted cognitive decline. However, the mean slope for SBP
      in the normotensive group showed an increase of 4.55mm Hg (increase from Time 1
      to Time 2 was 123mm Hg to 132 mm Hg) and was significant in a regression model
      predicting cognitive decline even after adjusting for covariates. These findings
      suggest an association between increasing SBP and cognitive decline for
      normotensive elderly in this study population.

PMID- 15842073
TI  - Supplementation of L-carnitine improves mitochondrial enzymes in heart and
      skeletal muscle of aged rats.
AB  - Aging is characterized by a general decline in physiological functions that
      affects many tissues and increases the risk of death. Deterioration of
      mitochondria, the major source and target of reactive oxygen species (ROS), is
      implicated in aging and a variety of age-related diseases. In the present study,
      the activities of citric acid cycle enzymes, such as isocitrate dehydrogenase,
      alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate
      dehydrogenase, were found to be decreased in aged rats as well as that of
      electron-transferring enzymes such as NADH dehydrogenase and cytochrome c
      oxidase. After supplementation of carnitine to aged rats, the activities of these
      enzymes reverted nearer to that of young control rats. These findings suggest
      that L-carnitine improves the activities of mitochondrial enzymes, increases the
      electron flow through the electron transport chain, and improves reducing
      equivalence, thereby improves energy status in aged rats.

PMID- 15842074
TI  - Career-span analyses of track performance: longitudinal data present a more
      optimistic view of age-related performance decline.
AB  - Sport scientists (Starkes, Weir, Singh, Hodges, & Kerr, 1999; Starkes, Weir, &
      Young, 2003) have suggested that prolonged training is critical for the
      maintenance of athletic performance even in the face of predicted age-related
      decline. This study used polynomial regression analyses to examine the
      relationship between age and running performance in the 1500 and 10,000 metre
      events. We compared the age and career-longitudinal performances for 15 male
      Canadian Masters athletes with a cross-sectional sample of performances at
      different ages. We hypothesized that the 30 years of uninterrupted training
      characteristic of this longitudinal sample would moderate the patterns of age
      related decline (retention hypothesis); alternatively, the cross-sectional data
      were expected to demonstrate pronounced age-related decline (quadratic
      hypothesis). Investigators performed multimodel regression analyses on the age
      and performance data. Based on the absence (for longitudinal data) or presence
      (for the cross-sectional data) of significant quadratic components in second
      order polynomial models, the authors found support for their respective
      hypotheses. The longitudinal data showed that running performance declined with
      age in a more linear fashion than did cross-sectional data. Graphical trends
      showed that the moderation of age-related decline appeared greater for the
      longitudinal 10 km performances than for the 1500m event.

PMID- 15842075
TI  - Music enhances category fluency in healthy older adults and Alzheimer's disease
      patients.
AB  - Exposure to some music, in particular classical music, has been reported to
      produce transient increases in cognitive performance. The authors investigated
      the effect of listening to an excerpt of Vivaldi's Four Seasons on category
      fluency in healthy older adult controls and Alzheimer's disease patients. In a
      counterbalanced repeated-measure design, participants completed two, 1-min
      category fluency tasks whilst listening to an excerpt of Vivaldi and two, 1-min
      category fluency tasks without music. The authors report a positive effect of
      music on category fluency, with performance in the music condition exceeding
      performance without music in both the healthy older adult control participants
      and the Alzheimer's disease patients. In keeping with previous reports, the
      authors conclude that music enhances attentional processes, and that this can be
      demonstrated in Alzheimer's disease.

PMID- 15842076
TI  - An interprofessional role for veterinary medicine in human health promotion and
      disease prevention.
AB  - In the past, veterinarians have participated in interprofessional collaboration
      to support the health promotion and disease prevention goals and objectives
      described in the United States Department of Health and Human Services' (DHHS)
      Healthy People 2010. Such projects have resulted from collaboration resulting
      from a writing competition, the DHHS's Secretary's Award for Innovations in
      Health Promotion and Disease Prevention (Secretary's Award). The Secretary's
      Award, which interfaces with Healthy People 2010, has been effectively used as a
      means of training community-responsive veterinary students in a variety of
      interprofessional collaborations. All future health care professionals should be
      trained in innovative interprofessional problem solving, the 'art of thinking
      outside the box', and the importance of responsiveness to the needs of the
      community. These health professional students' collaborative efforts are vital
      for the continual improvement of any nation's health care system in the 21st
      century.

PMID- 15842077
TI  - Joined-up working' between early years professionals and speech and language
      therapists: moving beyond 'normal' roles.
AB  - This paper draws on research conducted for the Nuffield Foundation (Mroz et at,
      2002) which looked at the knowledge, skills and confidence of early years
      professionals in relation to young children's speech and language development.
      Key findings from the project are reported in relation to the efficacy of initial
      and post-qualification training in preparing professionals for the identification
      and support of children with communication problems. The discussion centres
      around early years practitioners' experiences of working with speech and language
      therapists and the needs which they expressed, both for inter-professional
      training and for modes of working together.

PMID- 15842078
TI  - Integrating health and social care: implications for joint working and community
      care outcomes for older people.
AB  - In England, the theme of promoting collaborative working between social and
      primary health care remains high on the policy agenda. The underlying assumption,
      largely untested, is that a greater degree of structural integration benefits
      service users. This paper reports the findings from a feasibility study comparing
      two models of joint working and examining the relative impact of personal
      characteristics, service use and co-location on the likelihood of older people
      remaining in the community. Baseline standardised interviews with 79 older people
      aged 75 + with complex needs in two social services departments were carried out
      following referral, covering social circumstances, physical and mental health and
      services received, with follow-up interviews after six months. Contacts between
      social workers and primary care were tracked. The findings suggest that co
      location does not necessarily lead to substantially closer interprofessional
      working in terms of greater contact between social workers and GPs or social
      workers and community nurses. Factors affecting outcome were degree of cognitive
      impairment, intensity of home care received and whether the older person lived
      alone. Whatever the model of collaborative working, its effects on remaining in
      the community must be assessed in the wider context of the characteristics and
      services received by older people.

PMID- 15842079
TI  - An exploration of the health and social wellbeing needs of looked after young
      people--a multi-method approach.
AB  - This study, which was undertaken in Northern Ireland, aimed to identify how the
      promotion of the health and social wellbeing of looked after young people could
      be enhanced using a four-stage triangulated research design employing qualitative
      and quantitative elements. Stage 1 sought to identify relevant health issues from
      a representative sample of case files and found low uptake of statutory medical
      assessments, relatively few physical health problems and higher levels of mental
      health and behavioural problems including self-esteem and self-image issues.
      Stage 2 sought to ascertain, through two focus groups, the views of those caring
      for looked after young people foster carers and residential social workers.
      Findings showed that both groups perceive themselves in a health promoting role
      with the main issues encountered being the need for support in issues such as sex
      education and access to sources of help and aids to health promotion. Stage 3
      sought to listen to the needs and concerns of the young people and their parents
      through a series of semi-structured interviews. These revealed the need of
      parents for involvement with their child's care and identification of the social
      worker as holding primary responsibility for health. Young people had positive
      views of health, identified stressors and perceived that too much help was given
      in relation to health issues; social workers were preferred for discussion of
      sensitive subjects. It was concluded that the multiple needs of young people give
      excellent opportunities for the development of interdisciplinary working in the
      context of multi-sectoral involvement to support effective health promotion
      interventions.

PMID- 15842080
TI  - Mentoring for nurses in general practice: an Australian study.
AB  - This paper presents findings from a project conducted to recommend a national
      framework for mentoring for general practice nurses in Australia. The first phase
      identified challenges and key issues; the second and third phases (reported here)
      engaged practice nurses and general medical practitioners in discussion to
      advance thinking on the topic. Outcomes revolved around seven core areas: role
      confusion and diversity of practice nursing; lack of a defined career pathway for
      practice nurses; professional isolation of practice nurses; need for general
      practitioner support; expectations of mentoring; importance of resourcing and
      infrastructure; and roles, skills and qualities of mentors. Implications of these
      for the development of a systemic approach to supporting nurses in general
      practice are discussed, taking into account the inter-professional context and
      special working relationship between nurses and doctors. Findings revealed keen
      support for the idea of mentoring for nurses in general practice and indicate
      success will depend on appropriate resourcing and infrastructure through
      national, state and local coordination processes.

PMID- 15842081
TI  - Core topics of health care ethics. The identification of core topics for
      interprofessional education.
AB  - OBJECTIVES: The aim of this project was to identify core topics of health care
      ethics that could be taught through an inter-professional approach to
      undergraduate education. DESIGN: Five nominal group technique workshops. SETTING
      AND PARTICIPANTS: Teaching staff from different professional disciplines in our
      university (nursing branches, occupational therapy and physiotherapy). RESULTS:
      Seven core topics of health care ethics that are common across all disciplines
      were identified. However participants in all workshops identified the need for
      case studies used in teaching and learning to be specific to the clinical setting
      encountered by the student. CONCLUSION: Despite the identification of core topics
      that apply to all disciplines, caution should be taken when seeking to integrate
      these into an inter-professional undergraduate programme. There is evidence from
      other studies that students have difficulty in transferring knowledge from one
      context to another. In view of this, an inter-professional approach to health
      care ethics teaching to a group, members of which do not encounter shared
      clinical ethical problems may be inappropriate. It is suggested that inter
      professional learning in undergraduate health care ethics should focus on
      facilitating learning in the clinical area with students who share similar
      ethical encounters, in which case the learning will be truly inter-professional.

PMID- 15842082
TI  - Portrait of occupational therapy.
AB  - The profession of occupational therapy promotes individuals to achieve health and
      wellness through engagement in meaningful occupations of daily living. This
      occupation-focused profession plays a critical role in health care in a multitude
      of settings with a wide range of clients. The paper highlights a global overview
      of the philosophies of occupational therapy, the current international practices
      in occupational therapy, the education of therapists, and the roles of law and
      professional societies that govern the practice of occupational therapy.

PMID- 15842083
TI  - Disparities and discrimination in health care: an introduction.
AB  - Racial disparities in health care and health outcomes are a disturbing feature of
      the American health care system. Efforts to reduce or ameliorate these
      disparities must be informed by an understanding of the factors that underlie and
      contribute to them. The papers in this issue are based on a recent conference
      that was held at the University of Chicago to address this problem. Socioeconomic
      status is an important determinant of health, and socioeconomic disparities are
      major determinants of the racial disparities in health. These socioeconomic
      disparities are complicated by access to health insurance, geographic factors,
      and unhealthy behaviors. Geographic disparities, both regional and local, also
      contribute to racial disparities in health. Moreover, current disparities in the
      health of adult populations may reflect socioeconomic disparities that prevailed
      during their intrauterine or early infant development. There seems little
      evidence that either overt or unconscious discrimination on the part of
      physicians is an important cause of racial disparities in health; blaming
      physicians for this problem is counterproductive. Improving the quality of
      medical care holds the promise not only of improving health for all Americans,
      but of decreasing the racial disparities in health care that are so troubling
      today.

PMID- 15842084
TI  - The Institute of Medicine report: too quick to diagnose bias.
AB  - The Institute of Medicine report, Unequal Treatment: Confronting Racial and
      Ethnic Disparities in Health Care, claims that medical studies document a
      systematic causal relationship between race and disparities in health inputs and
      outcomes among individuals of different races. This article argues that the
      majority of studies are not powerful enough to establish a causal link, since
      they do not sufficiently control for differences among patients that happen to
      correlate with race, and it outlines a powerful audit study that could isolate
      any effect of race on health care decisions. Even if there are race-based
      disparities in health inputs, evaluations of welfare and policy prescriptions
      should be based on health outcomes, since the relationship between care and
      health is, at least in some cases, weak.

PMID- 15842085
TI  - Disparities and discrimination in health care coverage: a critique of the
      Institute of Medicine study.
AB  - The 2003 Institute of Medicine (IOM) study on Unequal Treatment takes the strong
      position that many of the current disparities in health care by race are
      attributable to forms of conscious and unconscious discrimination by health care
      providers. The study, however, is flawed by imprecise definitions of
      discrimination that fail to distinguish between differences in treatment due to
      breakdown in communications and differences in the treated population that are
      prompted by invidious motives of health care providers. It is doubtful that
      hidden forms of discrimination are prevalent in a profession whose professional
      norms are set so strongly against it. In addition, the IOM relies too
      uncritically on similar studies in unrelated fields to show the ostensible forms
      of discrimination. These errors have adverse social consequences. A false
      diagnosis of discrimination where none exists will send a false signal to members
      of racial minorities that may induce them to avoid receiving needed medical care
      and instead pursue costly and ineffective remedial devices that will take away
      funds better spent on providing direct health care.

PMID- 15842086
TI  - Geographic variation in health care and the problem of measuring racial
      disparities.
AB  - In its study of racial and ethnic disparities in health care, the Institute of
      Medicine (IOM) concluded that there were large and significant disparities in the
      quality and quantity of health care received by minority groups in the United
      States. This article shows that where a patient lives can itself have a large
      impact on the level and quality of health care the patient receives. Since black
      or Hispanic populations tend to live in different areas from non-Hispanic white
      populations, location matters in the measurement and interpretation of health
      (and health care) disparities. There is wide variation in racial disparities
      across geographic lines: some areas have substantial disparities, while others
      have equal treatment. Furthermore, there is no consistent pattern of disparities:
      some areas may have a wide disparity in one treatment but no disparity in
      another. The problem of differences in quality of care across regions, as opposed
      to racial disparities in care, should remain the target of policy makers, as
      reducing quality disparities would play a major role in improving the health care
      received by all Americans and by minority Americans in particular.

PMID- 15842087
TI  - American medicine and the politics of race.
AB  - Straw men play a major role in the debate over racial disparity in American
      medicine. Most have been deployed by the disparities-denying right, but
      progressives intent on "outing" racism have sent forth their share. This essay
      flushes out the straw men while attempting to understand the competing moral
      premises that drive the politics of health care disparity. At bottom, arguments
      about the scope of disparity and discrimination in medical care are disputes
      about the appropriate scope of personal responsibility for life circumstances.
      Further research into the factors that correlate with racial differences in
      health care can shed light on the circumstances that bring about these
      differences. Whether these circumstances, once understood, should be deemed
      acceptable is a moral and political matter, and sharp differences over the scope
      of personal and public responsibility for these circumstances are inevitable.
      Such disagreements, however, distract us from efforts to reach common ground
      solutions to agreed-upon inequities in health care.

PMID- 15842088
TI  - Three tests for measuring unjustified disparate impacts in organ transplantation:
      the problem of "included variable" bias.
AB  - Civil rights statutes often prohibit two distinct types of discrimination,
      referred to as "disparate treatment" and "disparate impact." Disparate treatment
      is race-contingent decision making. But even decision making that is not affected
      by people's race may still produce an unjustified disparate impact. For example,
      a race-neutral transplantation preference for allografts with partial antigen
      matches might produce an unjustified disparate impact on African Americans with
      end-stage renal disease. The transplantation preference might make it harder for
      African Americans to receive a transplant without significantly increasing the
      chance of transplant survival. Because disparate impact and disparate treatment
      claims have distinct elements, they require distinct methods of statistical
      testing. This article analyzes three different ways of testing unjustified
      disparate impacts in organ transplantation, which I will call the traditional
      test, the omitted variable test, and the outcome test. Each of these methods of
      testing for disparate impact are attuned to the problem of "included variable"
      bias. Controlling statistically for nonracial variables may actually bias the
      analysis and mask the existence of unjustified disparate impacts.

PMID- 15842089
TI  - Correlation and causation: a comment.
AB  - Some purely methodological comments are made on the pitfalls and difficulties in
      making causal inferences from observational data, including in studies of
      disparity in medicine. The ideas of spurious correlation and measurement error
      are discussed with an eye towards their impact upon inferences about causality,
      and cautions are offered about over-reliance upon testing hypotheses.

PMID- 15842090
TI  - Measuring disparate impacts and extending disparate impact doctrine to organ
      transplantation.

PMID- 15842091
TI  - Step into my zapatos, doc: understanding and reducing communication disparities
      in the multicultural informed consent setting.
AB  - Current informed consent standards are aimed at promoting an equitable and
      ethical environment for conducting research across diverse patient populations.
      This paper explores the possible effects of ethnicity and culture on the consent
      process for pediatric cancer clinical trials. Informed consent discussions were
      observed, recorded, transcribed, and coded. Question asking by parents and
      clinician/parent word ratios were used to create an interactivity measure, or "I
      score." Visual analog scales were used to rate the clarity of specific
      explanations. Cases were sorted into two groups on the basis of parents' self
      reported ethnicity: Caucasian (n=79, 56%) and minority (predominantly Latino)
      parents (n=61, 44%). Chi-square and t-tests were used to compare the groups. A
      series of logistic regression analyses (controlling for ethnicity and SES) were
      run for variables that showed statistically significant differences (p < 0.05).
      Our findings suggest that the content and quality of the informed consent process
      is linked to parental ethnicity, or clinician attitudes toward parental
      ethnicity. These findings are discussed in terms of current perspectives on
      culture and "cultural competence" in health care. Further research is needed to
      understand how cultural factors affect outcomes such as parental understanding,
      decision making, mutual trust, and satisfaction within the informed consent
      process.

PMID- 15842092
TI  - Full disclosure: telling patients when not being a research subject is a good
      choice.
AB  - Informed consent to participation in research generally requires giving a person
      information about the alternatives to being in the research study. It is quite
      common, however, for research subjects not to be given one particularly
      significant piece of information: the possibility of obtaining the "new"
      treatment being studied directly from a doctor without participating in the
      study. Since many people enroll in studies precisely to get such a new treatment,
      they frequently would prefer that option--which guarantees them that new
      treatment--to enrolling in a study where there is only a 50% chance of getting
      the new treatment. This issue becomes more complicated in the context of
      pediatric oncology research, since physician-researchers in this field have
      entered into a unique informal agreement not to offer such new treatments outside
      of research studies. That agreement, which in effect forces physicians to behave
      in a manner that subordinates the well-being of some of their current patients to
      that of future patients, is ethically and legally questionable.

PMID- 15842093
TI  - Changes in the disparities in chronic diseases during the course of the 20th
      century.
AB  - Longitudinal studies support the proposition that the extent and severity of
      chronic conditions in middle and late ages are to a large extent the outcome of
      environmental insults at early ages, including in utero. Data from the Early
      Indicators Project, undertaken at the Center for Population Economics, suggest
      that the range of differences in exposure to disease has narrowed greatly over
      the course of the 20th century, that age-specific prevalence rates of chronic
      diseases were much lower at the end of the 20th century than they were at the
      beginning of the last century or during the last half of the 19th century, and
      that there has been a significant delay in the onset of chronic diseases over the
      course of the 20th century. These trends appear to be related to changes in
      levels of environmental hazards and in body size. These findings have led
      investigators to posit a synergism between technological and physiological
      improvements. This synergism has contributed to reductions in inequality in real
      income, body size, and life expectancy during the 20th century.

PMID- 15842094
TI  - Breast cancer and race: a rising tide does not lift all boats equally.
AB  - African American women have a lower overall incidence of breast cancer but a
      higher overall mortality than do white women. African American women with breast
      cancer present for medical care at an earlier age, with more advanced stage
      disease, and with higher-risk tumor biology. While the advanced stage at
      presentation and higher-risk tumor biology appear to account for much of the
      excess mortality in African American women, differences persist even after
      controlling for these factors. This paper discusses the factors that may
      contribute to differences in survival and differences in stage at diagnosis
      between African American and white women.

PMID- 15842095
TI  - Black-white differences in the economic value of improving health.
AB  - This article examines how differences in longevity over time and across groups
      add to the typical measures of economic progress and intergroup differentials. We
      focus on gains for and differences between groups defined both by race (black and
      white) and by gender, relying on willingness to pay as our measure of the
      economic value of gains in longevity. Measured at birth, the gains for white
      males between 1968 and 1998 were about 245,000 dollars per person, while the
      gains for black males were far larger, about 390,000 dollars per person. The
      gains for women were somewhat smaller, with white females gaining about 150,000
      dollars per person and black females gaining about 305,000 dollars per person.
      Our estimates suggest that differences in income explain about 1/3 to 1/2 of the
      current black-white gap in longevity.

PMID- 15842096
TI  - [Management of polymyositis and dermatomyositis: from clinical trials to
      practice].

PMID- 15842097
TI  - [Autoimmune diseases and IgIV: commitment of the French Laboratory of Division
      and Biotechnology].

PMID- 15842098
TI  - [Treatment by IgIV of polymyositis and dermatomyositis: literature review].

PMID- 15842099
TI  - [Physiopathology of polymyositis and dermatomyositis, mechanism of action of
      intravenous immunoglobulins].

PMID- 15842100
TI  - [Dermatomyositis: dermatologic approach].

PMID- 15842103
TI  - Geropsychiatric inpatient care: what is state of the art?
AB  - Although dedicated geropsychiatric units have been available for many years,
      little information is available about them as a group. This article describes a
      survey that was developed to learn what type of resources, policies, or
      procedures geropsychiatric inpatient units employed to promote best nursing care
      practices. Physical changes to the unit and enhanced staff training were
      components of the current units and were consistently identified as needing
      enhancement to move to the next level of excellence. An unanticipated outcome was
      survey respondents' interest in becoming a part of a network of individuals who
      provide inpatient geropsychiatric care.

PMID- 15842104
TI  - The impact of medical issues in inpatient geriatric psychiatry.
AB  - At an advanced age, serious medical and psychiatric illnesses frequently
      coalesce. Often, the need for admission to inpatient geriatric psychiatric care
      arises from coexisting medical problems. While cognitive and behavioral
      interventions are important, the complexity of physical comorbidities usually
      becomes the focus of hospitalization and requires intensive medical treatments.
      This paper describes adaptations made in one metropolitan geriatric psychiatry
      unit in order to better treat complex patients who experience both medical and
      psychiatric illness. The need for all members of the interdisciplinary team to
      expand their practice and the importance of complementary approaches of
      psychiatry and medicine are emphasized.

PMID- 15842105
TI  - Managing perplexing patients: the case of Helen.
AB  - The challenges faced in provision of high quality and effective care to geriatric
      psychiatric inpatients are substantial for all members of the interdisciplinary
      team. Common care dilemmas, including the interplay of social, medical, and
      psychiatric factors in treating complex patients, are perhaps best understood by
      examining such a case. The hypothetical case of "Helen" illustrates the multi
      dimensional and often perplexing care needs of patients admitted multiple times
      for inpatient care. Linked nursing diagnoses, outcomes and interventions, and
      interdisciplinary care plans emphasize the changing care needs of such patients.

PMID- 15842106
TI  - New graduate orientation program in a geriatric psychiatric inpatient setting.
AB  - With the geriatric population increasing, so will their needs for mental health
      care. However, attracting nurses to work with mentally ill older adults can be
      challenging. This article describes and illustrates methods successfully used by
      one hospital to attract, orient, and mentor new graduate nurses to work in
      geropsychiatric nursing--the New Graduate Residency Program (NGRP). The
      importance of supportive collaborative roles within nursing leadership staff is
      emphasized. Although the NGRP is a viable option for meeting the needs of older
      patients, additional strategies are needed to increase the numbers of
      geropsychiatric nurses overall, and these are discussed.

PMID- 15842107
TI  - The Young Gerontological Nurse Clinician Program: an innovative geropsychiatric
      nursing recruitment strategy.
AB  - Historically, graduate nurses are not attracted to older adults or geriatric
      care. Innovative strategies, such as the Young Gerontological Nurse Clinician
      Program (YGNCP) initiated by the John A. Hartford Center for Geriatric Nursing
      Excellence at the University of Iowa, are needed to promote geriatric nursing as
      a challenging and rewarding practice focus. The YGNCP, which provides early,
      positive, self-directed experiences for nursing students under the direction and
      supervision of faculty and expert clinical mentors, shows excellent potential for
      recruiting nurses to clinical and leadership positions in geriatric and
      geropsychiatric care.

PMID- 15842108
TI  - Rapid change in status: the case of William.
AB  - In most geropsychiatric inpatient settings, the focus of care is reduction,
      management, or alleviation of psychiatric signs and symptoms through a
      combination of behavioral and pharmacologic interventions. However, unidentified
      or evolving medical conditions among frail older patients may precipitate rapid
      and unanticipated changes in status. The case of "William" illustrates how prompt
      adjustments in nursing care, collaboration within and between the geropsychiatric
      unit and other hospital services, and close working relationships with family may
      facilitate unexpected end-of-life decisions and promote quality of care.

PMID- 15842109
TI  - A geropsychiatric unit without walls.
AB  - The continued population growth of people over the age of 65 correlates with the
      growth in the number of older people who experience a mental health crisis or
      frank mental illness. Currently there is a paucity of treatment programs that are
      specialized for the geropsychiatric patient. Given the limitations of finances
      and human resources as well as the constraints sometimes imposed by regulatory
      agencies, interdisciplinary health care workers are challenged to provide optimum
      care in traditional settings. This article describes how an inpatient psychiatric
      unit can be modified to replicate some of the best practices of a designated
      geropsychiatric unit with positive results.

PMID- 15842110
TI  - We in public health have in some fashion not been achieving the goals that we
      have set for ourselves.

PMID- 15842112
TI  - Vitamin or supplement use among adults, behavioral risk factor surveillance
      system, 13 states, 2001.
AB  - OBJECTIVE: The authors examined vitamin/supplement (V/S) use and its relationship
      to sociodemographics, health behaviors, and health conditions among adults in 13
      states. METHODS: This investigation used 2001 data from a cross-sectional study
      of non-institutionalized adults aged > or = 18 years, the Behavioral Risk Factor
      Surveillance System. RESULTS: Of 45,415 respondents with complete data (18,723
      males and 26,692 females), 56.5% (n=5,652) reported current V/S use. After
      adjusting for age, sex, race/ethnicity, and education, the authors found a
      statistically significant association between V/S use and positive health risk
      behavior (adjusted odds ratio [OR]=1.46; p<0.001). Also, WS use was found to
      increase with age (p<0.001). No association was found between V/S use and the
      absence of specific chronic disease conditions (adjusted OR=0.93; p=0.052).
      CONCLUSIONS: People who used V/S in the states surveyed were more likely to
      demonstrate positive health risk behaviors than those who did not report V/S use.
      Thus it appears that individuals who are most likely to use V/S are least likely
      to need V/S. It is crucial that individuals report quantity and frequency of V/S
      use when providing medical or diet histories to health care providers.

PMID- 15842111
TI  - Rethinking race/ethnicity, income, and childhood asthma: racial/ethnic
      disparities concentrated among the very poor.
AB  - OBJECTIVE: Past studies of the prevalence of childhood asthma have yielded
      conflicting findings as to whether racial/ethnic disparities remain after other
      factors, such as income, are taken into account. The objective of this study was
      to examine the association of race/ethnicity and family income with the
      prevalence of childhood asthma and to assess whether racial/ethnic disparities
      vary by income strata. METHODS: Cross-sectional data on 14,244 children aged <18
      years old in the 1997 National Health Interview Survey were examined. The authors
      used logistic regression to analyze the independent and joint effects of
      race/ethnicity and income-to-federal poverty level (FPL) ratio, adjusting for
      demographic covariates. The main outcome measure was parental report of the child
      having ever been diagnosed with asthma. RESULTS: Bivariate analyses, based on
      weighted percentages, revealed that asthma was more prevalent among non-Hispanic
      black children (13.6%) than among non-Hispanic white children (11.2%; p<0.01),
      but the prevalence of asthma did not differ significantly between Hispanic
      children (10.1%) and non-Hispanic white children (11.2%; p=0.13). Overall, non
      Hispanic black children were at higher risk for asthma than non-Hispanic white
      children (adjusted odds ratio [OR]=1.20; 95% confidence interval [CI] 1.03,
      1.40), after adjustment for sociodemographic variables, including the ratio of
      annual family income to the FPL. Asthma prevalence did not differ between
      Hispanic children and non-Hispanic white children in adjusted analyses (adjusted
      OR=0.85; 95% CI 0.71, 1.02). Analyses stratified by income revealed that only
      among children from families with incomes less than half the FPL did non-Hispanic
      black children have a higher risk of asthma than non-Hispanic white children
      (adjusted OR=1.99; 95% CI 1.09, 3.64). No black vs. white differences existed at
      other income levels. Subsequent analyses of these very poor children that took
      into account additional potentially explanatory variables did not attenuate the
      higher asthma risk for very poor non-Hispanic black children relative to very
      poor non-Hispanic white children. CONCLUSIONS: Non-Hispanic black children were
      at substantially higher risk of asthma than non-Hispanic white children only
      among the very poor. The concentration of racial/ethnic differences only among
      the very poor suggests that patterns of social and environmental exposures must
      overshadow any hypothetical genetic risk.

PMID- 15842113
TI  - Influence of cigarette smoking on the overall perception of dental health among
      adults aged 20-79 years, United States, 1988-1994.
AB  - OBJECTIVE: Investigation into the relationship between lifestyle factors
      (particularly cigarette smoking) and perceived oral health has been limited. Data
      from the third National Health and Nutrition Examination Survey (NHANES II), 1988
      1994, were used to explore this relationship in a large sample of U.S. adults.
      METHODS: This study used data on 13,357 dentate participants in NHANES III aged
      20-79 years. In NHANES III, information on perceived dental health,
      sociodemographic attributes, smoking status, frequency of dental visits, dental
      insurance, and general health perception were collected during a home interview,
      and oral health status was assessed at a mobile examination center. RESULTS:
      Overall, 34.4% of individuals in the study sample reported having an unfavorable
      perception of their dental health by qualifying it as "fair" or "poor."
      Furthermore, 46.6% of smokers had an unfavorable dental health perception,
      compared to 28.3% of non-smokers. An interaction between smoking and
      race/ethnicity was found in logistic regression modeling. Stratified results show
      that cigarette smoking was not a significant predictor for an unfavorable dental
      health perception among individuals who self-identified as Mexican American, but
      smoking was a significant predictor for an unfavorable dental health perception
      among those who identified as non-Hispanic black or non-Hispanic white.
      CONCLUSIONS: This is the first study to describe the effects of smoking on dental
      health perception while controlling for examined oral health status. Because
      perceived dental health is a potential indicator for dental care utilization, a
      better knowledge of the factors that influence dental health perception is not
      only important for dental services planning, but also for understanding oral
      health-related quality of life issues. Additionally, given that smoking may
      negatively affect dental health perception, these findings have potential
      implications for smoking cessation activities conducted by dental care providers.

PMID- 15842114
TI  - Pap smear rates among Haitian immigrant women in eastern Massachusetts.
AB  - OBJECTIVE: Given limited prior evidence of high rates of cervical cancer in
      Haitian immigrant women in the U.S., this study was designed to examine self
      reported Pap smear screening rates for Haitian immigrant women and compare them
      to rates for women of other ethnicities. METHODS: Multi-ethnic women at least 40
      years of age living in neighborhoods with large Haitian immigrant populations in
      eastern Massachusetts were surveyed in 2000-2002. Multivariate logistic
      regression analyses were used to examine the effect of demographic and health
      care characteristics on Pap smear rates. RESULTS: Overall, 81% (95% confidence
      interval 79%, 84%) of women in the study sample reported having had a Pap smear
      within three years. In unadjusted analyses, Pap smear rates differed by ethnicity
      (p=0.003), with women identified as Haitian having a lower crude Pap smear rate
      (78%) than women identified as African American (87%), English-speaking Caribbean
      (88%), or Latina (92%). Women identified as Haitian had a higher rate than women
      identified as non-Hispanic white (74%). Adjustment for differences in demographic
      factors known to predict Pap smear acquisition (age, marital status, education
      level, and household income) only partially accounted for the observed difference
      in Pap smear rates. However, adjustment for these variables as well as those
      related to health care access (single site for primary care, health insurance
      status, and physician gender) eliminated the ethnic difference in Pap smear
      rates. CONCLUSIONS: The lower crude Pap smear rate for Haitian immigrants
      relative to other women of color was in part due to differences in (1)
      utilization of a single source for primary care, (2) health insurance, and (3)
      care provided by female physicians. Public health programs, such as the cancer
      prevention programs currently utilized in eastern Massachusetts, may influence
      these factors. Thus, the relatively high Pap rate among women in this study may
      reflect the success of these programs. Public health and elected officials will
      need to consider closely how implementing or withdrawing these programs may
      impact immigrant and minority communities.

PMID- 15842115
TI  - Orofacial pain: patient satisfaction and delay of urgent care.
AB  - OBJECTIVE: Accomplishing the Healthy People 2010 goal of eliminating disparities
      in oral disease will require a better understanding of the patterns of health
      care associated with orofacial pain. This study examined factors associated with
      pain-related acute oral health care. METHODS: The authors used data on 698
      participants in the Florida Dental Care Study, a study of oral health among
      dentate adults aged 45 years and older at baseline. RESULTS: Fifteen percent of
      the respondents reported having had at least one dental visit as the result of
      orofacial pain. The majority of the respondents reportedly delayed contacting a
      dentist for at least one day; however, there was no difference between
      respondents reporting pain as the initiating symptom and those with other
      problems. Once respondents decided that dental services were needed, those with a
      painful symptom were nearly twice as likely as those without pain to want to be
      seen immediately. Rural adults were more likely than urban adults to report
      having received urgent dental care for a painful symptom. When orofacial pain
      occurred, those who identified as non-Hispanic African American were more likely
      than those who identified as non-Hispanic white to delay care rather than to seek
      treatment immediately, and women were more likely then men. Having a pain-related
      oral problem was associated with significantly less satisfaction with the
      services provided; non-Hispanic African American respondents were less likely
      than non-Hispanic white respondents to report being very satisfied, and rural
      residents were less likely than urban residents. Furthermore, men were more
      likely than women to suffer with orofacial pain without receiving either
      scheduled dental care or an urgent visit. CONCLUSIONS: Barriers to care are
      complex and likely to be interactive, but must be understood before the goals of
      Healthy People 2010 can be accomplished.

PMID- 15842116
TI  - Recent incarceration independently associated with syringe sharing by injection
      drug users.
AB  - OBJECTIVES: Few prospective studies are available on the relationship between
      incarceration and HIV risk among injection drug users (IDUs). The authors
      evaluated self-reported rates of syringe sharing and incarceration among a cohort
      of IDUs. METHODS: This study analyzed syringe lending by HIV-infected IDUs and
      syringe borrowing by HIV-negative IDUs among participants enrolled in the
      Vancouver Injection Drug Users Study (VIDUS). Since serial measures for each
      individual were available, variables potentially associated with each outcome
      (syringe lending and borrowing) were evaluated using generalized estimating
      equations for binary outcomes. RESULTS: The study sample consisted of 1,475 IDUs
      who were enrolled into the VIDUS cohort from May 1996 through May 2002. At
      baseline, 1,123 (76%) reported a history of incarceration since they first began
      injecting drugs. Of these individuals, 351 (31%) reported at baseline that they
      had injected drugs while incarcerated. Among 318 baseline HIV-infected IDUs,
      having been incarcerated in the six months prior to each interview remained
      independently associated with syringe lending during the same period (adjusted
      odds ratio [OR]=1.33; 95% confidence interval [CI] 1.06, 1.69; p=0.015).
      Similarly, among the 1,157 baseline HIV-negative IDUs, having been incarcerated
      in the six months prior to each interview remained independently associated with
      reporting syringe borrowing during the same period (adjusted OR=1.26; 95% CI
      1.12, 1.44; p<0.001). CONCLUSIONS: Incarceration was independently associated
      with risky needle sharing for HIV-infected and HIV-negative IDUs. This evidence
      of HIV risk behavior should reinforce public health concerns about the high rates
      of incarceration among IDUs.

PMID- 15842117
TI  - A population-based analysis of pneumococcal disease mortality in California, 1989
      1998.
AB  - OBJECTIVES: Pneumococcal disease is an important cause of vaccine-preventable
      mortality. It is important to understand the burden and distribution of mortality
      so that prevention efforts can be targeted appropriately. This study evaluated
      pneumococcal disease mortality and its demographic correlates in California from
      1989 to 1998. METHODS: Deaths due to pneumococcal disease were identified from
      statewide vital records data using multiple cause-coded information. Denominator
      data were obtained from estimates from the California Department of Finance.
      Crude and age-adjusted mortality rates and 95% confidence intervals were
      calculated for each age, gender, and racial/ethnic group. RESULTS: The age
      adjusted pneumococcal disease mortality rate was 2.05 deaths per 100,000
      population. Mortality was highest in elderly individuals (reaching 38.29 deaths
      per 100,000 population in individuals older than age 85). Age-adjusted mortality
      rates were elevated in the African American race/ethnicity group (2.96 deaths per
      100,000 population) and males (2.67 deaths per 100,000 population). The majority
      of individuals who died of pneumococcal disease (78.9%) fell into at-risk groups
      indicated for vaccination. The majority of all pneumococcal deaths were caused by
      pneumococcal pneumonia. Mortality was seasonal, reaching a peak in the winter
      months. A decreasing trend in mortality was observed over the 10-year period
      examined. CONCLUSIONS: Pneumococcal disease remains a significant cause of
      vaccine-preventable mortality in the California population. Greater efforts must
      be made to vaccinate at-risk individuals, especially those in demographic groups
      at highest risk of death.

PMID- 15842118
TI  - Illegal alcohol sales and use of alcohol control policies at community festivals.
AB  - OBJECTIVES: The primary goals of this study were to assess the propensity for
      alcohol sales to underage customers and obviously intoxicated customers at
      community festivals, and to assess the prevalence of alcohol control policies at
      these events. A secondary goal was to identify server and festival
      characteristics and festival policies related to the likelihood of illegal
      alcohol sales. METHODS: We conducted pseudo-underage purchase attempts at 43
      festivals and pseudo-intoxicated purchase attempts at 50 festivals to assess the
      likelihood of illegal sales. Research staff made observations at festivals and
      contacted festival planners by telephone following each event to assess which
      alcohol policies were implemented. We conducted backwards stepwise multivariate
      analyses for each purchase attempt outcome to identify policies and
      characteristics related to likelihood of illegal alcohol sales. RESULTS: Pseudo
      intoxicated buyers purchased beer in 89% of 95 attempts (standard deviation
      [SD]=0.31) and pseudo-underage buyers were able to purchase beer in 50% of 82
      attempts (SD=0.50). All festival planners reported having at least two of the 10
      alcohol policies we assessed, but no festival had implemented all 10 policies.
      Server characteristics were not related to either purchase attempt outcome. In
      the multivariate analyses, having more alcohol control policies was related to a
      greater likelihood of illegal sales to intoxicated customers; however, having
      more alcohol control policies was associated with a lesser likelihood of alcohol
      sales to underage customers. Restricting the number of servings per person was
      also associated with a lesser likelihood of alcohol sales to underage customers.
      CONCLUSIONS: Propensity for illegal alcohol sales at festivals is very high.
      Research is needed to identify interventions to prevent illegal alcohol sales at
      these events.

PMID- 15842119
TI  - Escherichia coli O157:H7 outbreak associated with consumption of ground beef,
      June-July 2002.
AB  - OBJECTIVE: A case-control and environmental study tested the hypothesis that
      purchasing and eating ground beef from a specific source was the cause of a
      cluster of cases of hemolytic uremic syndrome (HUS) and Escherichia coli (E.
      coli) O157:H7 gastroenteritis. METHODS: A case-control study comparing risk
      factors was conducted over the telephone on nine case-patients with 23 selected
      controls. An environmental investigation was conducted that consisted of
      reviewing beef handling practices at a specific local supermarket and obtaining
      ground beef samples from the store and two households with case-patients.
      RESULTS: The analysis of the case-control study showed that eight case-patients
      (89%) purchased ground beef at Grocery Chain A compared with four controls who
      did not develop illness (17%) (matched odds ratio=undefined; 95% confidence
      interval 2.8, infinity; p=0.006). The environmental investigation showed that
      Grocery Chain A received meat from Meatpacker A. Laboratory analysis of meat
      samples from Meatpacker A and Grocery Chain A and stool samples from some
      patients recovered an identical strain of E. coli O157:H7 according to pulse
      field gel electrophoresis. CONCLUSIONS: Both the case-control and environmental
      studies showed that purchasing ground beef at Grocery Chain A, which received
      ground beef from Meatpacker A, was the major risk factor for illness in eight
      case-patients; the ninth case-patient was found to be unrelated to the outbreak.
      Furthermore, meat from Meatpacker A was associated with a nationwide outbreak of
      E. coli O157:H7 illness that resulted in the second largest recall of beef in
      U.S. history at the time.

PMID- 15842120
TI  - Risk factors for lead poisoning among Cuban refugee children.
AB  - OBJECTIVES: This study was designed to explore whether parental activities such
      as repairing cars, welding, and rebuilding car batteries are risk factors for
      lead poisoning among Cuban refugee children in Miami-Dade County. METHODS: The
      authors performed a cross-sectional study of 479 children aged 12-83 months who
      had lived in Cuba during the six months prior to immigrating to the U.S. Lead
      levels were obtained, and parents provided information on demographics,
      home/neighborhood environment in Cuba prior to immigration, family/occupational
      factors prior to immigration, and child behavior factors. RESULTS: Of 479
      children, 30 (6.3%) had elevated blood lead levels (EBLLs), defined as > or = 10
      microg/dL, based on the Centers for Disease Control and Prevention action level.
      In multivariate analysis, racial/ethnic identification other than white, living
      in a home built after 1979, car repair in the home or yard, eating paint chips,
      and male sex were independently associated with EBLL. CONCLUSIONS: Risk factors
      for lead poisoning among immigrant children may differ from those among U.S.-born
      children. Screening of immigrant children who may have been exposed in their
      country of origin and education of immigrant parents about lead exposure hazards
      associated with activities such as car repair should be considered in the design
      of lead poisoning prevention and control programs.

PMID- 15842121
TI  - Self-assessment in the measurement of public health workforce preparedness for
      bioterrorism or other public health disasters.
AB  - OBJECTIVE: The purpose of this study was to examine effective ways to evaluate
      public health workers' competence for preparedness. METHODS: The Public Health
      Ready project, developed by the National Association of County and City Public
      Health Officials and the Centers for Disease Control and Prevention, is a pilot
      program designed to prepare local public health agencies to respond to emergency
      events. Workers at a Public Health Ready site (N=265) rated their need for
      training and their competence in meeting generic emergency response goals.
      Cluster analysis of cases was conducted on the self-assessed need for training.
      RESULTS: Three groups of workers emerged, differing in their overall ratings of
      need for training. A given worker tended to report similar needs for training
      across all training goals. CONCLUSIONS: In this study, workers' ratings of need
      for training may reflect an overall interest in training rather than need for
      training in a particular area. Caution should be exercised in interpretation when
      generic goals and self-assessment are used to measure need for training. Future
      assessments of training needs may be more effective if they use objective
      measures of specific local plans.

PMID- 15842122
TI  - Tobacco use among American Indians in Oklahoma: an epidemiologic view.
AB  - OBJECTIVES: With the exception of national surveys that sample the entire U.S.
      population, little information exists on tobacco habits among American Indians.
      This study is a comparison of tobacco use findings in the 1990s among American
      Indians in Oklahoma, a state with a large and diverse American Indian population
      (39 tribes). METHODS: Data on current tobacco use are presented from two
      statewide surveys, the Oklahoma Youth Tobacco Survey and the Native American
      Behavioral Risk Factor Survey, as well as two large epidemiologic studies of
      chronic disease among American Indians-the Cherokee Diabetes Study and the Strong
      Heart Study. Three of these four sources of data involve research/surveys
      exclusively about American Indians. RESULTS: Nontraditional use of tobacco by
      American Indians occurs frequently, according to each instrument. Initiation to
      this habit begins in middle school and increases dramatically during high school.
      After age 50, reporting by individuals that they currently smoke declines
      steadily. CONCLUSIONS: Despite sampling different individuals for the surveys and
      different tribes for the epidemiologic research, results were comparable in age
      groups that overlapped. These findings support national data indicating that
      American Indians have higher prevalence rates of smoking than other racial/ethnic
      groups. American Indians report smoking on average about a half a pack of
      cigarettes per day. Individuals reporting using tobacco solely for ceremonial
      purposes were far fewer than habitual users. Buying tobacco products in American
      Indian smoke shops helps tribal economies; this fact needs to be considered for
      prevention programs to succeed.

PMID- 15842124
TI  - Molloy v Meier and the expanding standard of medical care: implications for
      public health policy and practice.

PMID- 15842123
TI  - Tobacco industry manipulation of research.

PMID- 15842125
TI  - Collaborative research in a faith-based setting: Columbus Congregations for
      Healthy Youth.

PMID- 15842126
TI  - Radiation therapy may improve survival of premenopausal women with breast cancer
      involving axillary lymph nodes.

PMID- 15842127
TI  - Modifiable vascular risk factors are associated with diabetic neuropathy in type
      1 diabetes.

PMID- 15842128
TI  - Commentary: A new approach to atherogenic dyslipidemia.

PMID- 15842129
TI  - Cholesterol lowering in diabetes. New evidence supports aggressive LDL-C targets.
AB  - Recent guidelines for treating patients with diabetes categorize the disorder as
      a coronary heart disease (CHD) equivalent and urge aggressive treatment of
      modifiable risk factors, such as plasma levels of low-density lipoprotein
      cholesterol (LDL-C). In this article, Dr Rosenson discusses the rationale for
      cholesterol lowering in patients with diabetes, the lipoprotein abnormalities
      that accompany insulin resistance, and the prognostic significance of high LDL
      particle numbers. He also highlights major findings from recent clinical trials
      to explore statin therapy and other treatment strategies for lowering lipoprotein
      levels in this patient population.

PMID- 15842130
TI  - Taking aim at HDL-C. Raising levels to reduce cardiovascular risk.
AB  - Although statin therapy has revolutionized management of coronary heart disease
      (CHD), the lowering of low-density lipoprotein cholesterol (LDL-C) levels is not
      the whole story. Increased plasma concentrations of high-density lipoprotein
      cholesterol (HDL-C) have a cardioprotective effect that is just as important for
      reducing risk of heart attack and stroke. In this article, Dr McGovern examines
      the evidence that provides the rationale for HDL-C as a therapeutic target for
      cardiovascular risk reduction.

PMID- 15842131
TI  - Rare cause of facial asymmetry. Progressive facial hemiatrophy.

PMID- 15842132
TI  - Guiding prostate cancer treatment choices. Early detection means more options for
      more men.
AB  - Prostate cancer accounts for one third of nondermatologic cancers in men.
      Fortunately, early detection and technology have evolved to the point that an
      increasing number of men have more than one treatment option. These choices
      include prostatectomy, irradiation, hormone therapy, cryotherapy, and
      observation. However, each is associated with adverse effects and produces a
      different outlook. In this article, Dr Sweat explores these options and how they
      can be discussed with patients and tailored to meet their individual needs.

PMID- 15842133
TI  - The exercise prescription.

PMID- 15842134
TI  - [Methodology of integrative Chinese and Western medicine].

PMID- 15842135
TI  - [Effect of Chinese herbs on expression of aquaporin 3,4 gene in gastric mucosa of
      patients with Pi-Wei Damp-Heat syndrome].
AB  - OBJECTIVE: To explore the relationship between Pi-Wei Damp-Heat Syndrome (PWDHS)
      with expression of aquaporin (AQP) 3,4 gene in gastric mucosa and the effects of
      Qingre Huashi Recipe (QHR) on the expression. METHODS: Sixty-eight patients with
      chronic superficial gastritis were differentiated into Pi-Wei Damp-Heat Syndrome
      group (PWDHS, n = 53, 19 cases with predominant Dampness, 14 cases with
      predominant Heat, 20 cases with Dampness equal to Heat) and Pi deficiency
      Syndrome group (PDS, n = 15). The PWDHS were treated with QHR. The expression of
      AQP 3,4 gene in the two groups were determined by fluorescence quantitative
      polymerase chain reaction (FQ-PCR). RESULTS: Expression of AQP 3 gene in PWDHS
      was higher than that in PDS and the healthy group, but the difference showed no
      statistical significance. Expression of AQP 4 gene in PWDHS was obvious higher
      than that in PDS and the healthy group (P <0.05 or P <0.01), but the difference
      of AQP 4 gene expression between PDS and the healthy group was insignificant.
      Comparison among various sub-types of PWDHS showed that the AQP 4 gene expression
      in the predominant dampness > dampness equal to heat> predominant heat. AQP 3,4
      gene expression in PWDHS was significantly decreased after QHR treatment,
      especially in the cases with predominant dampness syndrome (P <0.01), approaching
      that in the healthy group and PDS. CONCLUSION: Abnormal expression of AQP 3,4
      gene may be one of the possible mechanisms of PWDHS pathogenesis, Chinese herbs
      could influence AQP 3,4 gene expression to play a key role in treatment.

PMID- 15842136
TI  - [Clinical observation on effect of weichangshu in treating diabetic
      gastroparesis].
AB  - OBJECTIVE: To observe the effect of Weichangshu (WCS) in treating diabetic
      gastroparesis (DGP). METHODS: Ninety-six patients with DGP were randomly divided
      into two groups. Besides the same conventional blood glucose controlling regimen
      was given to both groups, WSC was given to the treated group and Mosapride
      Citrate tablet to the control group additionally. The treatment course for them
      was 4 weeks. Therapeutic effect on clinical syndromes was assessed, the fasting
      and 2-hr postprandial blood glucose, antro-duodenal interdigestive migrating
      motor complex (MMC) and electrogastrogram (EGG) were measured before and after
      treatment. RESULTS: The therapeutic effect in the two groups were similar with no
      statistical significant difference. The time of MMC phase II was shortened, time
      of MMC phase III prolonged, and the constriction amplitude of which increased
      after treatment in both groups, showing significant difference as compared to
      those before treatment (P < 0.05). EGG were significantly changed after treatment
      mainly manifested as increase of proportional dominant frequency (PDF) and
      strengthening of proportional dominant amplitude (PDP ) (P <0.05 or P < 0.01).
      Besides, WSC also promoted the decrease of post-prandial blood glucose.
      CONCLUSION: WSC has dual effect in promoting gastric motility and decreasing
      blood glucose, with less adoerst reaction.

PMID- 15842137
TI  - [Observation on therapeutic effect of jianpi huoxue herbs combined with
      chemotherapy in treating post-operational colonic cancer patients].
AB  - OBJECTIVE: To observe and compare the therapeutic effect of Jianpi Huoxue herbs
      (JPHXH) combined with chemotherapy (CT) in treating post-operational colonic
      cancer patients with Pi deficiency Syndrome (PDS). METHODS: Adopting randomized
      control trial method, 64 patients were divided into two groups. The treated group
      (n = 43) received JPHXH plus CT and the control group ( n = 21 ) received CT
      alone. A treatment course of 3 months was applied to both groups. Therapeutic
      effect, changes of PDS and incidence of adverse reaction in the two groups were
      observed. RESULTS: The tumor remission rate in the treated group and the control
      group was 39.5 % and 33.3 %, respectively. The effective rate on PDS in the
      treated group and the control group was 72.1% and 19.0%, respectively, showing
      significant difference (P < 0.01). The incidence of adverse reaction was lower in
      the treated group than that in the control group (P < 0.05). CONCLUSION: JPHXH is
      effective in treating post-operational colonic cancer patients with PDS and
      relieving the adverse reaction of chemotherapy to certain extent.

PMID- 15842138
TI  - [Comparative study on effects of puerarin and granulocyte colony-stimulating
      factor in treating acute myocardial infarction].
AB  - OBJECTIVE: To compare the effects of puerarin and granulocyte colony-stimulating
      factor (G-CSF) in treating acute myocardial infarction (AMI) and on the size of
      infarcted area and cytokines. METHODS: Seventy-nine patients with anterior AMI
      were randomly divided into three groups, they were treated with conventional
      Western medical treatment, but to the puerarin group (PG) and the G-CSF group
      (GCG) puerarin and G-CSF was given additionally, respectively. The infarcted
      size, plasma G-CSF, matrix metalloproteinase-9 (MMP-9), serum interleukin-6 (IL
      6) and tumor necrosis factor-alpha (TNF-alpha) were detected before and after
      treatment. RESULTS: The infarcted size was positively correlated to the levels of
      G-CSF, MMP-9, IL-6 and TNF-alpha before treatment ( r = 0.45, 0.42, 0.44 and
      0.42, P<0.01 ). The infarcted size in the PG and the GCG decreased on the 28th
      day (P<0.01), the level of G-CSF, MMP-9, IL-6 and TNF-alpha in the PG on the 7th
      day all decreased (P<0.05), but these indexes in the GCG increased (P<0.05),
      while those in the control group were unchanged (P>0.05). CONCLUSION: Puerarin
      and G-CSF are effective in decreasing infarcted size, but their effects on
      cytokines are different entirely.

PMID- 15842139
TI  - [Chronic arsenic poisoning caused by long-term taken Niuhuang Ninggong tablet: a
      report of 2 cases].

PMID- 15842140
TI  - [Clinical observation on treatment of multiple organ dysfunction syndrome with
      auxiliary treatment of Shennong No.33].
AB  - OBJECTIVE: To observe the therapeutic effect of Shennong No. 33 (SN33) in
      treating multiple organ dysfunction syndrome (MODS) by APACHE II and APACHE II
      scoring. METHODS: One hundred and twenty-nine patients of MODS were randomly
      divided into the treated group (n = 72) and the control group (n = 57), they were
      treated with comprehensive therapy and to the treated group, SN33 was given
      additionally. The changes of APACHE II and APACHE III scores and blood endotoxin
      level were observed at the time points of within 24 hrs after hospitalization,
      and the 3rd, 5th and 7th day. RESULTS: In the treated group, 50 patients survived
      and 22 died, while in the control group, 25 survived and 32 died. The APACHE II
      and APACHE III scores of the survivors were higher than those of the decedent
      (P<0.05), which in the treated group was lower than those in the control group
      (P<0.05). The blood level of endotoxin in the treated group was also lower than
      that in the control group (P<0.05). CONCLUSION: SN33 in treating MODS could
      improve patients' condition, lead to the lowering of APACHE scores. APACHE
      scoring system could be applied as the criteria for evaluating the condition and
      prognosis of critical patients, and the APACHE III scoring is more accurate.

PMID- 15842141
TI  - [Clinical study on aitongping capsule in treating cancerous pain].
AB  - OBJECTIVE: To explore the therapeutic effect and mechanism of Aitongping capsule
      (ATP) in treating cancerous pain. METHODS: Sixty cancer patients were randomly
      divided into two groups, 30 patients in the treated group took ATP and 30
      patients in the control group took diclofenac, 1 week of treatment was applied.
      The relevant clinical conditions of cancerous pain, the content of plasma beta
      endorphin (beta-EP) and c-AMP, hemorheological index, improuement of life quality
      of patients, occurrence rate of adverse reaction were observed before and after
      treatment. RESULTS: The total effective rate in the treated group and in the
      control group was 90.0 % and 83.3%, respectively, difference between them showed
      no significance. However, there were significant difference between the two
      groups in such aspects as the degree of pain relieving, the decrease of pain
      episodes, the shortening persistent time of pain and the initiation time of
      analgesic action and prolonged analgesic duration, the decrease of tenderness and
      percussion pain, the increase of plasma beta-EP content and the decrease of cAMP
      (P< 0.05 or P< 0.01). The evidences also showed that it was better in improving
      quality of life, ameliorating hemorheologic indexes and reducing incidence of
      adverse reaction in the treated group than in the control group (P <0.05 or P
      <0.01). CONCLUSION: ATP has affirmative effect on cancerous pain, its analgesic
      effect may be associated with the increasing of plasma beta-EP content,
      decreasing of cAMP level and ameliorating of hemorheologic indexes.

PMID- 15842142
TI  - [Clinical study on treatment of pulmonary interstitial fibrosis with ginkgo
      extract].
AB  - OBJECTIVE: To observe the effect of ginkgo extract on pulmonary interstitial
      fibrosis. METHODS: Forty-five patients with pulmonary interstitial fibrosis were
      randomly divided into two groups, the treated group (n = 30) received ginkgo
      biloba extract 1 g, three times a day; the control group received prednisone 30
      mg, once a day, the therapeutic course for both groups was 3 months. Changes of
      clinical symptoms, pulmonary function, arterial partial pressure of oxygen,
      computerized tomography (CT), interleukin-6 (IL-6), interleukin-8 (IL-8) and
      tumor necrosis factor-alpha(TNF-alpha) in the two groups were observed before and
      after treatment. RESULTS: The efficacy of treatment in the two groups showed
      insignificant difference, clinical symptoms, pulmonary function, arterial partial
      pressure of oxygen were improved after treatment (P < 0.05), and the levels of IL
      6, IL-8 and TNF-alpha significantly decreased after treatment as compared with
      those before treatment in the two groups. The occurrence of pulmonary infection
      was less in the treated group than that in the control group (P <0.05).
      CONCLUSION: Ginkgo is effective in treating pulmonary interstitial fibrosis.

PMID- 15842143
TI  - [Study on correlationship of TCM syndrome type and expression of ICAM-1, CD62P in
      patients with ischemic stroke].
AB  - OBJECTIVE: To study the correlationship between TCM Syndrome type with changes of
      neutrophil surface intercellular adhesion molecule-1 (ICAM-1) and platelet
      membrane P selectin (CD62P) in patients with ischemic stroke for exploring the
      pathogenesis of the disease. METHODS: Seventy-two patients with ischemic stroke
      were dividcd into 3 typing groups according to TCM syndrome-differentiation, the
      Meridian-phlegm stagnancy group (MPS), the visceral phlegm-heat accumulation
      group (VPHA) and the qi-deficiency with blood stasis group (QDBS), 24 in each
      group. Besides, a control group consisted of 24 healthy subjects was set up.
      Blood levels of ICAM-1 and CDP62 expression were monitored by flow cytometry.
      RESULTS: Blood levels of ICAM-1 and CD62P expression in ischemic stroke patients
      were significantly higher than those in healthy subjects (P < 0.01). Among the
      three type groups, ICAM-1 expression was significantly higher in MPS than that in
      the VPHA and the QDBS group (P<0.01), and CD62P expression in the MPS and the
      QDBS group was significantly higher than that in the VPHA (P <0.01). CONCLUSION:
      Blood levels of ICAM-1 and CD62P expression in different typing of patients with
      ischemic stroke are different. ICAM-1 expression reflects the pathological state
      of phlegm retention or phlegm-stasis mutual bindings, CD62P expression reflected
      the blood stasis state in organism, these evidences suggest that MPS may be the
      key pathogenic factor of ischemic stroke.

PMID- 15842144
TI  - [Effect of Shuangshen Tongguan Recipe on nuclear factor-kappa B signal pathway
      and myocardial junction-mediated intercellular communication in acute myocardial
      ischemia/reperfusion injured model rats].
AB  - OBJECTIVE: To investigate the effects of Shuangshen Tongguan Recipe (SSTG) on
      myocardial nuclear factor-kappa B (NF-kappaB) signal pathway, expression of
      myocardial junction intercellular communication (MJIC) connexin 43 (Cx43), and
      infarcted myocardial size and weight of the rats' heart after acute myocardial
      ischemia/reperfusion (I/R) damage. METHODS: Model rat of I/R injury was
      established by coronary arterial ligating/ releasing. The infarcted myocardial
      size and weight were determined by N-BT staining, expression of NF-kappaB p65 in
      myocardial tissue and Cx43 were determined by immunohistochemical method,
      contents of serum tumor necrosis factor-alpha(TNF-alpha) and intercellular
      adhesion molecule-1 (ICAM-1) were measured by ABC-ELISA. RESULTS: The myocardial
      infarcted size and weight, expression of NF-kappaB p65, contents of serum TNF
      alpha and ICAM-1 of I/R injured rats in the model group were significantly
      increased (P<0.05), while Cx43 degraded markedly after modeling. These changes
      were restored after treated with SSTG (P <0.05). CONCLUSION: Serious myocardial
      infarction occurs after ischemia/reperfusion injury, combined with NF-kappaB
      signal pathway activation and severe Cx43 degradation. SSTG could inhibit the
      activation of NF-kappaB, the over-excretion of TNF-alpha and ICAM-1 in serum, and
      the degradation of Cx43 to decrease the myocardial infarcted size and weight.

PMID- 15842145
TI  - [Effect of folium panax quinquefolium saponins on apoptosis of cardiac muscle
      cells and apoptosis-related gene expression in rats with acute myocardial
      infarction].
AB  - OBJECTIVE: To observe the effect of Folium Panax quinquefolium saponins (PQS) on
      apoptosis of cardiac muscle cells (CMCs) and apoptosis-related gene expression in
      rats with acute myocardial infarction (AMI). METHODS: Fifty Wistar rats were
      randomly divided into 5 groups, 40 rats underwent coronary ligation of left
      anterior descending branch to establish AMI rats model, while to the other 10
      rats in the sham-operation group, thoracotomy without coronary ligation was
      carried out. The AMI model rats in treated groups were treated with high-dosage
      PQS, low-dosage PQS, captopril respectively for 7 days, and those in the control
      group were treated with normal saline instead. Then, the apoptotic CMCs were
      labeled by TUNEL and the expression of Bcl-2 and Fas in cardiac muscle cells were
      determined by immunohistochemical methods. RESULTS: The apoptotic index of CMCs
      in the model rats (46.48%) was significantly higher than that in the sham
      operation group ( 1.03%, P<0.01 ). CMCs apoptosis rate in the low-dosage PQS
      group, the large-dosage group and the captopril group was 23.53 %, 17.58 % and
      25.17 %, respectively, all were significantly lower than that in the sham
      operation group (P<0.01). The expression of Bcl-2 gene was up-regulated and
      expression of Fas protein was down-regulated in the three treated groups.
      CONCLUSION: PQS can inhibit CMCs apoptosis in AMI rats, downregulate Fas protein
      expression and up-regulate Bcl-2 protein expression, and has antagonistic effect
      in myocardial ischemic injury.

PMID- 15842146
TI  - [Comparative study on effect of astragulus injection and interleukin-2 in
      enhancing anti-tumor metastasis action of dendrite cells].
AB  - OBJECTIVE: To compare the effect of Astragulus injection (AGI) and interleukin-2
      (IL-2) in enhancing anti-tumor metastasis action of dendrite cells (DCs) based
      vaccine. METHODS: C57BL/6 mice's myelogenic DCs were prepared and pre-sensitized
      by Mut1, a MHC class I-restricted tumor antigen polypeptide of Lewis lung cancer.
      Then the DCs were used to treat mice with metastatic lung cancer in combination
      with AGI or IL-2. Change of proportion of T-lymphocyte cell subsets in splenic
      cell was analyzed by flow cytometry, and the serum contents of IL-2 and IL-4 of
      the tumor bearing mice were detected by ELISA. RESULTS: After being treated with
      tumor antigen polypeptide sensitized DCs plus AGI or IL-2, the tubercle of lung
      cancer decreased, proportion of subsets CD4+T and CD8+T in mice's splenic cell
      increased, and serum IL-2/IL-4 ratio also increased obviously. During the
      observed period, the tumor developing rate in the immune mice treated with DCs
      combined treatment, either with IL-2 or with AGI, was lower than that in mice
      treated with DCs alone. CONCLUSION: Both AGI and IL-2 can enhance the anti-tumor
      metastasis action of DCs, effectively promote the immune response of tumor
      bearing host, therefore have obviously inhibitory effect on lung cancer
      metastasis in vivo. Their immune protective function in normal animals is even
      more evident.

PMID- 15842147
TI  - [Study on inhibitory effect of matrine on cyclooxygenase-2 expression in colon
      cancer HT-29 cell line].
AB  - OBJECTIVE: To explore the effect of matrine on cyclooxygenase-2 (COX-2)
      expression in colon cancer HT-29 cell line at the level of gene and protein.
      METHODS: Levels of mRNA and protein expression of COX-2, and its synthesized
      product prostaglandin E2 (PGE2) of colon cancer HT-29 cell line were detected by
      RT-PCR, Western-blot, ELISA respectively before and after treatment of matrine in
      different concentrations. RESULTS: Matrine had inhibitory effect on the mRNA and
      protein expression of COX-2, and synthesis of PGE2 in colon cancer HT-29 cell
      line, but had no effect on COX-1. When HT-29 cell line was treated with 2.0 mg/ml
      of matrine, the inhibitory rate on COX-2 mRNA expression were 100% at 6 hrs and 9
      hrs after treatment; the inhibitory rate on PGE2 synthesis was 63.8 % at 9 hrs
      after treatment; and that on COX-2 protein expression was 48% and 100% 12 hrs and
      24 hrs after treatment, respectively. CONCLUSION: Matrine has selective
      inhibitory effect on gene transcription, protein expression and functional
      activity of COX-2 in HT-29 cell line, which is time-dependent and concentration
      dependent within certain range of concentration and acting time.

PMID- 15842148
TI  - [Study on mechanism of tea polyphenols in inducing human lung cancer cell
      apoptosis in vitro].
AB  - OBJECTIVE: To investigate the apoptosis inducing effect of tea polyphenols (TPP)
      on human lung cancer cell (LCC) and its associative mechanism. METHODS: The
      apoptosis inducing effect of TPP on LCC in vitro, and its influence on expression
      of the related gene were determined by MTT assay, laser scanning confocal
      microscopy and flow cytometry. RESULTS: TPP in different concentration
      (50,100,200 and 400 microg/ml) had dose-dependent inhibitory effect on LCC, the
      inhibitory rate was 28.69+/-1.27% ,46. 19+/-1.79% ,64.61+/-1.29%, 75.90+/-1.96%,
      respectively. The inhibited LCC were blocked in (G0/G1 phase, and could not
      transferred to S and G2/ M phase of cell cycle. Meanwhile, TPP could induce
      apoptosis of LCC, the apoptotic rate being 4.76+/-0.11 %, 5.78+/-0.38 %, 10.06+/
      0.67 %, 24.44+/-0.44 %, respectively. Morphologic changes of cells were seen in
      laser scanning confocal microscopy observation. Compared to the control group,
      intracellular Ca2+ concentration, Annexin V expression, phospatase and tensin
      homologe deleted on chromosome ten (PTEN) protein and expression gradually
      increased, while Cyclin D1 protein expression gradually decreased in the TPP
      treated groups along with the increasing of TPS concentration. CONCLUSION: TTP
      can induce LCC apoptosis, the mechanism is related to the change of intracellular
      Ca2+ concentration, PTEN protein and Cyclin D1 protein expression.

PMID- 15842149
TI  - [Effect of nuclear factor-kappaB on differentiation of bone marrow stromal cells
      into neurons induced by baicalin in rats].
AB  - OBJECTIVE: To explore the effect of nuclear factor-kappaB (NK-kappaB) on
      differentiation of bone marrow stromal cells (MSC) into neurons induced by
      baicalin. METHODS: Using baicalin as main inducer, differentiation of rats' MSC
      was induced into NC in serum-free medium, at the same time, untreated cells were
      cultured in serum-free medium as the control group. The expression of NC special
      marker protein and the presence of NK-kappaB subunits RelA (P65) translocated
      into nucleus were determined by immunofluorescent cytochemical stain, the change
      of expression of NK-kappaB inhibitory protein (IkappaBalpha) were determined by
      Western blot, and the apoptotic index was assessed by terminal deoxynucleotidyl
      transferase-mediated d-UTP-biotin nick end labeling (TUNEL) assay. RESULTS: MSC
      displayed typical shape of NC and expressed several NC marker protein after
      induced by baicalin, while those changes were not revealed in the control group.
      but showed translocation of P65 from cytoplasm to nucleus, and the markedly
      reduction of IkappaBalpha expression, the apoptotic index being 28.2+/-6.1 %.
      After induced by baicalin, the P65 still revealed mainly in cytoplasm with the
      level of IkappaBalpha expression decreased lesser and the number of apoptosis
      cell (12.2+/-2.8%) lower than those in the control group, P <0.01. CONCLUSION:
      Baicalin could inhibit NK-kappaB activation, and it has certain effect in
      inducing the differentiation of MSC into NC.

PMID- 15842150
TI  - [Design and application of single case randomized controlled trial].
AB  - The principle, method, procedure, indicated subject and feasibility of
      application of single case randomized controlled trial (SCRCT) were reviewed in
      the article. In randomized controlled trials (RCT), the allocation unit can be a
      single case (random therapy), multiple cases (random allocation) or group such as
      family, class or community. Traditional Chinese medicine is good at treatment of
      chronic disease, Syndrome differentiation, the traits of TCM, requires multiple
      research methods. SCRCT is suitable for symptomatic treatment of chronic discase
      due to its convenience in observation, reduce individual divergence and low
      research cost. SCRCGT is characterized by using randomized method to carry out
      multiple crossover follow-up, to assess the efficacy of treatment for two
      therapeutic schemes.

PMID- 15842151
TI  - [Study on systematic bioloay and syndrome of traditional Chinese medicine].
AB  - The ideas and methodology of science since the later half of 15th century were
      reviewed in this article. It was indicated that reduction theory is the science
      studying existence, mainly the components and nature of things, and emergency
      theory is the science studying production, mainly involved in the production of
      new things, the scientific attitude in research work is to combine these two
      theories (the reductionism and holism). The adthor also pointed out that the
      combination of systematic biology with molecular biology, and the application of
      mathematical modeling are the new trend in research of life science. Research of
      "syndrome", a professional TCM term, is just consistent with this located at
      scientific frontier and highly comprehensive systematic biological theory. The
      integration of findings at molecular level obtained during the last several
      decades by reduction theory will push the research of "Syndrome" into the
      scientific frontier again.

PMID- 15842152
TI  - [Study on integrative point of traditional and western medicine--from
      "integrative disease and syndrome" to "integrative pathological process and
      syndrome"].
AB  - The clinical thinking modes of "integrative disease and Syndrome" and
      "integrative macroscopical Syndrome-differentiation and microscopical Syndrome
      differentiation" formed in the past half century were merely the primary train of
      thought and methodology of integrative traditional Chinese and Western medicine.
      In order to develop them to a higher level, stress should be put on the unity and
      holism of disordered organism and unity of function, structure and metabolism. It
      has long been ignored that a parallel and correlated relationship exists between
      the TCM Syndrome and pathological process of Western medicine, which is a common,
      set-formed and regular pathophysiological changes with certain development phase,
      presented in various diseases. Both have common features as that the same
      pathological process can be seen in different diseases and several pathological
      progresses can present in one disease, the same Syndrome also can be seen in
      different diseases and several Syndromes can present in a disease. Moreover, they
      have the compatible connotation and denotation. The author deduced that
      pathophysiological basis of main Syndrome is indeed the basic pathological
      process. Essence of Syndrome is the related pathological processes including
      abnormal changes in function, metabolism and morphological structure.

PMID- 15842153
TI  - [Short-term curative effect observation on treatment of tumor by Shengling liquid
      combined with intervene therapy].

PMID- 15842154
TI  - [Clinical observation on immunologic infertility treated by integrative Chinese
      and Western medicine].

PMID- 15842155
TI  - [Study on protective effect of Shenmai injection on hematopoiesis of bone marrow
      in acute leukemia patients with chemotherapy].

PMID- 15842156
TI  - [Discussion on English translation of Liuyin in TCM].

PMID- 15842157
TI  - [Application of uniform design in research of traditional Chinese medicine].
AB  - In the uniform design, all level number of experimental relevant factors are
      equally distributed in the range of experiment, each experimental point shows
      representation better. The times of experiment are reduced and the data obtained
      can be treated with computer. Uniform design is a potent tool in seeking for the
      optimal experimental condition or the optimal proportion of experiments. So, it
      is often used to study extraction and preparation form technology of TCM. In
      recent years, the uniform design has been used in the domain of traditional
      Chinese recipe and the compatibility of its component drugs. The study showed
      that the analytical results of TCM theory and that of uniform design are
      extremely consistent. As an optimal screening means in modernizing study on
      Chinese herbs, using uniform design in studying classical recipe, the "syndrome"
      corresponding recipe whereas it is helpful to deeply recognize the scientific
      connotation of "recipe syndrome".

PMID- 15842159
TI  - A good time to measure our success.

PMID- 15842158
TI  - [Schedule for diagnosis and treatment of irritable bowel syndrome with
      integrative Chinese and Western medicine (draft)].

PMID- 15842160
TI  - National advisory council on patient safety finds risk management's contributions
      and challenges.

PMID- 15842161
TI  - DEHP exposure questions lead to calls for caution.

PMID- 15842162
TI  - Education initiatives using distance learning technology.

PMID- 15842163
TI  - Risk retention groups find favor in the health care arena.

PMID- 15842164
TI  - Managing obligations: right of privacy and release of clinical records.

PMID- 15842165
TI  - Criminal actions. Hospital pleads guilty to wire fraud for medically unnecessary
      procedures. U.S. v. United Memorial Hospital, No. 1:01-CR-238 (W.D. Mich. Jan. 8,
      2003).

PMID- 15842166
TI  - Vicarious liability. Hospital liable for the actions of a non-employee
      radiologist. Mejia v. Community Hospital of San Bernardino, 99 Cal. App. 4th
      1448, 122 Cal. Rprtr. 233 (Ct. App. Cal. 2002).

PMID- 15842167
TI  - Protein promiscuity: drug resistance and native functions--HIV-1 case.
AB  - The association of a drug with its target protein has the effect of blocking the
      protein activity and is termed a promiscuous function to distinguish from the
      protein's native function (Tawfik and associates, Nat. Genet. 37, 73-6, 2005).
      Obviously, a protein has not evolved naturally for drug association or drug
      resistance. Promiscuous protein functions exhibit unique traits of evolutionary
      adaptability, or evolvability, which is dependent on the induction of novel
      phenotypic traits by a small number of mutations. These mutations might have
      small effects on native functions, but large effects on promiscuous function; for
      example, an evolving protein could become increasingly drug resistant while
      maintaining its original function. Ariel Fernandez, in his opinion piece, notes
      that drug-binding "promiscuity" can hardly be dissociated from native functions;
      a dominant approach to drug discovery is the protein-native-substrate transition
      state mimetic strategy. Thus, man-made ligands (e.g. drugs) have been
      successfully crafted to restrain enzymatic activity by focusing on the very same
      structural features that determine the native function. Using the successful
      inhibition of HIV-1 protease as an example, Fernandez illustrates how drug
      designers have employed naturally evolved features of the protein to suppress its
      activity. Based on these arguments, he dismisses the notion that drug binding is
      quintessentially promiscuous, even though in principle, proteins did not evolve
      to associate with man made ligands. In short, Fernandez argues that there may not
      be separate protein domains that one could term promiscuous domains. While
      acknowledging that drugs may bind promiscuously or in a native-like manner a la
      Fernandez, Tawfik maintains the role of evolutionary adaptation, even when a drug
      binds native-like. In the case of HIV-1 protease, drugs bind natively, and the
      initial onset of mutations results in drug resistance in addition to a dramatic
      decline in enzymatic activity and fitness of the virus. A chain of compensatory
      mutations follows this, and then the virus becomes fully fit and drug resistant.
      Ben Berkhout and Rogier Sanders subscribe to the evolution of new protein
      functions through gene duplication. With two identical protein domains, one
      domain can be released from a constraint imposed by the original function and it
      is thus free to move in sequence space toward a new function without loss of the
      original function. They emphasize that the forced evolution of drug-resistance
      differs significantly from the spontaneous evolution of an additional protein
      function. For instance, the latter process could proceed gradually on an
      evolutionary time scale, whereas the acquisition of drug-resistance is an all or
      nothing process for a virus, leading to the failure or success of therapy. They
      find no evidence to the thesis that resistance-mutations appear more rapidly in
      promiscuous domains than native domains. Berkhout and Sanders illustrate the
      genetic plasticity of HIV-1 by citing examples in which well-conserved amino acid
      residues of catalytic domains are forced to mutate under drug-pressure. HIV drug
      resistance biology is very complex. Instead of a viral protein, a drug can be
      targeted at a cellular protein. For example, Berkhout and Sanders claim, a drug
      targeted at the cellular protein CCR5 inhibits the binding of the viral envelope
      glycoprotein (Env) to CCR5. However, Env mutates so that it binds to the CCR5
      drug complex and develops drug resistance. Interestingly, CCR5 has not evolved to
      bind to Env, but to a series of chemokines. Andrzej Kloczkowski, Taner Sen, and
      Bob Jernigan point out the importance of protein motions for binding. They
      believe it is likely that different ligands can bind to the diverse protein
      conformations sampled in the course of normal protein conformational
      fluctuations. They have been applying simple elastic network models to extract
      the motions as normal modes, which yield relatively small numbers of
      conformations that are useful for developing protein mechanisms; while these are
      typically small motions, for some proteins they can be quite large in scale. One
      of the major advantages of the approach is that only relatively small numbers of
      modes are important contributors to the overall motion -- so the approach
      provides a way to systematically map out a protein's motions. These models
      successfully represent the conformational fluctuations manifested in the
      crystallographic B-factors, and often suggest motions related to protein
      functional behaviors, such as those observed for reverse transcriptase, where two
      dominant hinges clearly relate to the processing steps -- one showing anti
      correlation between the polymerase and ribonuclease H sites related to the
      translation and positioning of the nucleic acid chain, and another for opening
      and closing the polymerase site. Disordered proteins represent a more extreme
      case where the set of accessible conformations is much larger; thus they could
      offer up a broader range of possible binding forms. Whether evolution controls
      the functional motions for proteins remains little studied. Intriguingly, buried
      in the existing databases of protein-protein interactions may be information that
      can shed light on the extent of promiscuous binding among proteins themselves.
      Within these data there are cases where large numbers of diverse proteins have
      been shown to interact with a single protein; some of these could represent
      promiscuous protein-protein binding. Uncovering these promiscuous behaviors could
      be important for comprehending the details of how proteins can bind promiscuously
      to one another, and can exhibit even greater promiscuity in their binding to
      small molecules. The evolutionary routes, the dynamics of the target protein, and
      the many other aspects that need to be addressed while designing a drug that may
      dodge drug resistance, indicate the complexity and multi-disciplinary nature of
      the issue of drug resistance.

PMID- 15842168
TI  - A systematic search method for the identification of tightly packed transmembrane
      parallel alpha-helices.
AB  - Membrane proteins play a major role in number of biological processes such as
      signaling pathways. The determination of the three-dimensional structure of these
      proteins is increasingly important for our understanding of their structure
      function relationships. Due to the difficulty in isolating membrane proteins for
      X-ray diffraction studies, computational techniques are being developed to
      generate the 3D structures of TM domains. Here, we present a systematic search
      method for the identification of energetically favorable and tightly packed
      transmembrane parallel alpha-helices. The first step in our systematic search
      method is the generation of 3D models for pairs of parallel helix bundles with
      all possible orientations followed by an energy-based filter to eliminate
      structures with severe non-bonded contacts. Then, a RMS-based filter was used to
      cluster these structures into families. Furthermore, these dimers were energy
      minimized using molecular mechanics force field. Finally, we identified the
      tightly packed parallel alpha-helices by using an interface surface area. To
      validate our search method, we compared our predicted GlycophorinA dimer
      structures with the reported NMR structures. With our search method, we are able
      to reproduce NMR structures of GPA with 0.9A RMSD. In addition, by considering
      the reported mutational data on GxxxG motif interactions, twenty percent of our
      predicted dimers are within in the 2.0A RMSD. The dimers obtained from our method
      were used to generate parallel trimeric and tetramer TM structures of GPA and
      found that the structure of GPA might exist only in a dimer form as reported
      earlier.

PMID- 15842169
TI  - Secondary binding site of trypsin: revealed by crystal structure of trypsin
      peptide complex.
AB  - Designed synthetic heterochiral peptides, when added to porcine trypsin, resulted
      in reduction of enzyme activity. The crystal structure of a complex formed
      between porcine trypsin and a heterochiral hepta peptide Boc-Pro-DAsp-Aib-Leu-Aib
      Leu-Ala-NHMe has been determined at 1.9 A resolution. The hepta peptide does not
      bind at the active site, but is located in the interstitial region, and interacts
      with the calcium-binding loop (residues 60-80). The bound peptide interacts with
      the active site residue Ser195 through an acetate ion, and with Lys 60 mediated
      by water molecules. The structure, when compared with the other trypsin-peptide
      complexes, suggests that the flexibility of surface loops, concerted movement of
      the loops towards the active site, and the interaction of the bound peptide with
      Lys 60, may be responsible for the reduction in enzyme activity. This study
      provides a structural evidence for the earlier biochemical observation regarding
      the role of surface loops in the catalysis of the enzyme.

PMID- 15842170
TI  - Closed loops of TIM barrel protein fold.
AB  - The closed loops within the proteins of the TIM-barrel fold family are analyzed
      and compared sequence- and structure-wise. The size distribution of the closed
      loops of the TIM-barrels confirms universal preference to the standard size of 25
      30 residues. 3D structural RMSD comparisons of the closed loops and presentation
      of their sequences in binary form suggest that the TIM-barrel proteins are built
      from descendants of several types of basic closed loop prototypes. Comparison of
      these prototypes points to a likely common ancestor--the alpha helix containing
      closed loops of 28 amino acids. The presumed ancestor is characterized by
      specific binary consensus sequence.

PMID- 15842171
TI  - Dynamics of the native and the ligand-bound structures of eosinophil cationic
      protein: network of hydrogen bonds at the catalytic site.
AB  - Eosinophil Cationic Protein (ECP) is sequentially and structurally similar to
      ribonuclease A (RNase A). It belongs to the RNase A family of proteins and the
      RNA catalysis is essential to its biological function. In the present study, we
      have generated the dinucleotide-bound structures of ECP by docking the
      dinucleotides to a number of molecular dynamics (MD) generated ECP structures.
      The stability of the docked enzyme-ligand complexes was ascertained by extensive
      MD simulations. The modes of ligand binding are explored by essential dynamics
      studies. The role of water molecules in the stability of the complex and in the
      catalysis was investigated. The active site residues form a complex network of
      connections with the ligand and with a water molecule. The catalytic mechanism of
      the RNA cleavage is examined on the basis of the active site geometry obtained by
      the simulations.

PMID- 15842172
TI  - Molecular dynamics simulations of a nucleosome and free DNA.
AB  - All atom molecular dynamics simulations (10ns) of a nucleosome and of its 146
      basepairs of DNA free in solution have been conducted. DNA helical parameters
      (Roll, Tilt, Twist, Shift, Slide, Rise) were extracted from each trajectory to
      compare the conformation, effective force constants, persistence length measures,
      and fluctuations of nucleosomal DNA to free DNA. The conformation of DNA in the
      nucleosome, as determined by helical parameters, is found to be largely within
      the range of thermally accessible values obtained for free DNA. DNA is found to
      be less flexible on the nucleosome than when free in solution, however such
      measures are length scale dependent. A method for disassembling and
      reconstructing the conformation and dynamics of the nucleosome using Fourier
      analysis is presented. Long length variations in the conformation of nucleosomal
      DNA are identified other than those associated with helix repeat. These
      variations are required to create a proposed tetrasome conformation or to
      qualitatively reconstruct the 1.75 turns of the nucleosome's superhelix.
      Reconstruction of free DNA using selected long wavelength variations in
      conformation can produce either a left-handed or a right-handed superhelix. The
      long wavelength variations suggest 146 basepairs is a natural length of DNA to
      wrap around the histone core.

PMID- 15842173
TI  - Yeast nucleosome DNA pattern: deconvolution from genome sequences of S.
      cerevisiae.
AB  - Positional correlation analysis for the complete genome of Saccharomyces
      cerevisiae is performed with the aim to reveal possible chromatin-related
      sequence features. A strong periodicity with the period 10.4 bases is detected in
      the distance histograms for the dinucleotides AA and TT, with the characteristic
      decay distance of approximately 50 base pairs. The oscillations are observed as
      well in the distributions of other dinucleotides. However, the respective
      amplitudes are small, consistent with secondary effects, due to dominant
      periodicity of AA and TT. The observations are in accord with earlier data on the
      chromatin sequence periodicities and nucleosome DNA sequence patterns. The
      autocorrelations of AA and TT dinucleotides in yeast include also a counter-phase
      component. A tentative DNA sequence pattern for the yeast nucleosomes is
      suggested and verified by comparison of its autocorrelation plots with the
      respective natural autocorrelations. The nucleosome mapping guided by the pattern
      is in accord with experimental data on the linker length distribution in yeast.

PMID- 15842174
TI  - Towards an understanding of DNA recognition by the methyl-CpG binding domain 1.
AB  - CpG methylation determines a variety of biological functions of DNA. The
      methylation signal is interpreted by proteins containing a methyl-CpG binding
      domain (MBDs). Based on the NMR structure of MBD1 complexed with methylated DNA
      we analysed the recognition mode by means of molecular dynamics simulations. As
      the protein is monomeric and recognizes a symmetrically methylated CpG step, the
      recognition mode is an asymmetric one. We find that the two methyl groups do not
      contribute equally to the binding energy. One methyl group is associated with the
      major part of the binding energy and the other one nearly does not contribute at
      all. The contribution of the two cytosine methyl groups to binding energy is
      calculated to be -3.6 kcal/mol. This implies a contribution of greater than two
      orders of magnitude to the binding constant. The conserved amino acid Asp32 is
      known to be essential for DNA binding by MBD1, but so far no direct contact with
      DNA has been observed. We detected a direct DNA base contact to Asp32. This could
      be the main reason for the importance of this amino acid. MBD contacts DNA
      exclusively in the major groove, the minor groove is reserved for histone
      contacts. We found a deformation of the minor groove shape due to complexation by
      MBD1, which indicates an information transfer between the major and the minor
      groove.

PMID- 15842175
TI  - Homology modeling based solution structure of Hoxc8-DNA complex: role of context
      bases outside TAAT stretch.
AB  - The 3D structure of neither Hoxc8 nor Hoxc8-DNA complex is known. The repressor
      protein Hoxc8 binds to the TAAT stretch of the promoter of the osteopontin gene
      and modulates its expression. Over expression of the osteopontin gene is related
      to diseases like osteoporosis, multiple sclerosis, cancer et cetera. In this
      paper we have proposed a 3D structure of Hoxc8-DNA complex obtained by Homology
      modeling and molecular dynamics (MD) simulation in explicit water. The crystal
      structure (9ant.pdb) of Antennapedia homeodomain in complex with its DNA sequence
      was chosen as the template based on (i) high sequence identity (85% for the
      protein and 60% for the DNA) and (ii) the presence of the TAAT stretch in
      interaction with the protein. The resulting model was refined by MD simulation
      for 2.0ns in explicit water. This refined model was then characterized in terms
      of the structural and the interactional features to improve our understanding of
      the mechanism of Hoxc8-DNA recognition. The interaction pattern shows that the
      residues Ile(195), Gln(198), and Asn(199), and the bases S2-(4)TAATG(8) are most
      important for recognition suggesting the stretch TAATG as the "true recognition
      element" in the present case. A strong and long-lived water bridge connecting
      Gln(198) and the base of S1-C(7) complementary to S2-G(8) was observed. Our
      predicted model of Hoxc8-DNA complex provides us with features that are
      consistent with the available experimental data on Hoxc8 and the general features
      of other homeodomain-DNA complexes. The predictions based on the model are also
      amenable to experimental verification.

PMID- 15842176
TI  - DNA interaction with naturally occurring antioxidant flavonoids quercetin,
      kaempferol, and delphinidin.
AB  - Flavonoids are strong antioxidants that prevent DNA damage. The anticancer and
      antiviral activities of these natural products are implicated in their mechanism
      of actions. However, there has been no information on the interactions of these
      antioxidants with individual DNA at molecular level. This study was designed to
      examine the interaction of quercetin (que), kaempferol (kae), and delphinidin
      (del) with calf-thymus DNA in aqueous solution at physiological conditions, using
      constant DNA concentration (6.5 mmol) and various drug/DNA(phosphate) ratios of
      1/65 to 1. FTIR and UV-Visible difference spectroscopic methods are used to
      determine the drug binding sites, the binding constants and the effects of drug
      complexation on the stability and conformation of DNA duplex. Structural analysis
      showed quercetin, kaempferol, and delphinidin bind weakly to adenine, guanine
      (major groove), and thymine (minor groove) bases, as well as to the backbone
      phosphate group with overall binding constants K(que) = 7.25 x 10(4)M(-1), K(kae)
      = 3.60 x 10(4)M(-1), and K(del) = 1.66 x 10(4)M(-1). The stability of adduct
      formation is in the order of que>kae>del. Delphinidin with a positive charge
      induces more stabilizing effect on DNA duplex than quercetin and kaempferol. A
      partial B to A-DNA transition occurs at high drug concentrations.

PMID- 15842177
TI  - Discrimination between perfect and mismatched duplexes with oligonucleotide gel
      microchips: role of thermodynamic and kinetic effects during hybridization.
AB  - The efficiency of discrimination between perfect and mismatched duplexes during
      hybridization on microchips depends on the concentrations of target DNA in
      solution and immobilized probes, buffer composition, and temperature of
      hybridization and is determined by both thermodynamic relationships and
      hybridization kinetics. In this work, optimal conditions of discrimination were
      studied using hybridization of fluorescently labeled target DNA with custom-made
      gel-based oligonucleotide microchips. The higher the concentration of immobilized
      probes and the higher the association constant, the higher the concentration of
      the formed duplexes and the stronger the corresponding fluorescence signal, but,
      simultaneously, the longer the time needed to reach equilibrium. Since mismatched
      duplexes hybridize faster than their perfect counterparts, perfect-to-mismatch
      signal ratio is lower in transient regime, and short hybridization times may
      hamper the detection of mutations. The saturation time can be shortened by
      decreasing the probe concentration or augmenting the gel porosity. This improves
      the detection of mutations in transient regime. It is shown that the decrease in
      the initial concentration of oligonucleotide probes by an order of magnitude
      causes only 1.5-2.5-fold decrease of fluorescence signals after hybridization of
      perfect duplexes for 3-12 h. At the same time, these conditions improve the
      discrimination between perfect and mismatched duplexes more than two-fold. A
      similar improvement may be obtained using an optimized dissociation procedure.

PMID- 15842178
TI  - Computational evaluation of intermolecular interactions of a universal base 3
      nitropyrrole in stacked dimers and DNA duplexes.
AB  - The stacking interactions between a universal base of 3-nitropyrrole (3NP) and
      four canonical nucleobases were studied by means of ab initio molecular orbital
      calculations. The stabilities of the complexes are comparable to those of the
      stacked dimers of canonical bases reported previously. The detailed analysis of
      the interaction energies revealed the importance of the dipole-dipole interaction
      included in the Hartree-Fock terms to determine the geometry dependence of the
      stacking energies. It was also clarified that the dispersion energies included in
      the electron-correlation terms were essential to obtain adequate stabilities. The
      contribution of the nitro group was evaluated by the comparative studies of
      pyrrole and 3NP. The increased molecular dipole moment and surface are expected
      to account for the enhancement of the stability of the stacked dimers containing
      3NP. The force field parameters required for calculation of the molecular
      mechanics of 3NP were obtained for 3NP on the basis of these molecular orbital
      calculations. The energy-minimized structures obtained by the molecular mechanics
      calculations of 3NP accorded with those obtained by the molecular orbital
      calculations described above. A DNA duplex structure containing 3NP-A, 3NP-T, or
      3NP-C was calculated by use of these force field parameters. In the case of 3NP
      A, the computationally calculated structure was in good agreement with that
      previously determined by use of (1)H-NMR except for the orientation of the nitro
      group.

PMID- 15842179
TI  - Photon transmission study on conformational ordering of iota-carrageenan in CaCl2
      solution.
AB  - Coil-to-double helix (c-h) and double helix-to-dimer (h-d) phase transitions of
      iota-carrageenan in CaCl(2) solution upon cooling were studied using photon
      transmission technique. Photon transmission intensity, I(tr) was monitored
      against temperature to determine the (c-h) and (h-d) transition temperatures
      (T(ch) and T(hd)) and activation energies (DeltaE(ch) and DeltaE(hd)). An extra
      dimer-to-dimer (d-d) transition was also observed during cooling at low
      temperature region. However, upon heating dimers disappear to double helices by
      making dimer-to-double helix (d-h) transition. Further heating resulted double
      helix-to-coil (h-c) transition at high temperature region. T(dh) and T(ch)
      temperatures and DeltaE(dh) and DeltaE(hc) activation energies were also
      determined. It was observed that T(hc) and T(ch) temperatures and DeltaE(dh) and
      DeltaE(hd) activation energies do not effected by carrageenan content. However,
      T(hd), T(dh) and T(dd) temperatures and DeltaE(ch) and DeltaE(hc) activation
      energies were found to be strongly correlated to the carrageenan content in the
      system.

PMID- 15842181
TI  - Neurobiology and etiology of panic disorder.
AB  - Panic disorder entered the psychiatric nomenclature a quarter-century ago, and an
      explosion of studies followed. Defining the core phenomenology of panic disorder
      can be advanced by an understanding of its pathophysiology and exploration of its
      etiology. The lessons learned can guide the delivery of treatments to enhance the
      likelihood of achieving remission and the discovery of novel treatments for panic
      disorder.

PMID- 15842182
TI  - The implications of medical and psychiatric comorbidity with panic disorder.
AB  - The frequent presentation of patients with panic disorder in medical settings
      may, in part, be explained by the physical symptoms inherent in panic disorder.
      However, a number of medical disorders have symptoms that overlap with panic
      disorder symptoms, and elevated panic disorder prevalence is comorbid with a
      number of medical illnesses, including respiratory disorders, vestibular
      dysfunction, and hyperthyroidism and hypothyroidism. The presence of medical
      comorbidity complicates the identification, presentation, and treatment of panic
      disorder. In addition, comorbid mood disorders occur commonly and result in
      greater severity, poorer quality of life, and greater impairment. Recent work
      suggests that panic disorder occurs more commonly with bipolar disorder than
      major depressive disorder, resulting in substantial impairment, as well as poorer
      response to treatment. The implications of mood disorder and its medical
      comorbidity for the identification and treatment of panic disorder are discussed.

PMID- 15842183
TI  - Understanding and treating panic disorder in the primary care setting.
AB  - According to studies, the median prevalence of panic disorder in the primary care
      setting is 4%. Rates are higher among certain patient populations, such as those
      with cardiac (20% to 50%) or gastrointestinal presentations (28% to 40%).
      Consequently, patients with panic disorder are high utilizers of medical services
      and are heavily represented among patients classified as high health care
      utilizers, compared with other psychiatric or non-psychiatric groups. Despite its
      frequency in the primary care setting, panic disorder is significantly under
      recognized by medical providers. Corresponding with inadequate recognition is the
      substantial proportion of these patients who fail to receive appropriate
      treatment (pharmacotherapy and psychotherapy). Most experts have concluded that
      panic disorder is poorly managed in the primary care setting because of the
      process of care and patient engagement. In terms of process of care, primary care
      practice still operates on an acute disease model (leaving no time for initial
      patient education or follow-up), which is a poor fit for the management of
      chronic diseases. Insufficient patient engagement in treatment (i.e., being
      involved in the treatment process, "buying into" rationale for treatment, and
      being willing to collaborate with clinician and adhere to recommendations) is the
      second important contributor to inadequate treatment. Use of a chronic disease
      self-management approach would enhance treatment of panic disorder. This model
      requires that patients, in collaboration with the health care provider/system,
      take day-to-day responsibility for managing their illness by doing 3 things:
      adhering to recommended medical management, adopting improved health
      habits/coping skills, and assisting in ongoing monitoring of illness
      status/change. Future approaches to treating panic disorder in primary care would
      be enhanced by including assessments of patient beliefs and preferences, spending
      more time in preparing the patient for treatment, utilizing a simple
      pharmacotherapy algorithm, utilizing simple rating scales to monitor outcomes,
      and training providers in brief CBT interventions.

PMID- 15842184
TI  - The pharmacotherapy of panic disorder.
AB  - Panic disorder is common and associated with significant morbidity and
      dysfunction. The pharmacologic treatment of panic disorder is aimed at reducing
      or eliminating panic attacks, avoidance behavior, anticipatory anxiety, and
      comorbid conditions--and substantially improving and normalizing overall function
      and quality of life. Antidepressants and benzodiazepines remain the current
      mainstays of pharmacotherapy for panic disorder, although other novel agents and
      strategies are becoming available and may add effective alternatives to the
      therapeutic armamentarium.

PMID- 15842185
TI  - Cognitive-behavioral therapy and the treatment of panic disorder: efficacy and
      strategies.
AB  - In this article, we review the efficacy and applications of cognitive-behavioral
      therapy (CBT) for panic disorder. Research supports CBT as an effective first
      line treatment of panic disorder that offers relatively quick onset of action and
      long-term maintenance of treatment benefits. These characteristics, plus the
      acceptability, tolerability, and cost-efficacy of CBT, make it an especially
      attractive treatment option for panic disorder. We review these findings as well
      as some newer developments in the field including research on emotional
      acceptance, the importance of context in extinction learning, and the use of CBT
      in combination with pharmacotherapy.

PMID- 15842187
TI  - "Invention is hard, but dissemination is even harder".

PMID- 15842188
TI  - Changes in physical therapy providers' use of fall prevention strategies
      following a multicomponent behavioral change intervention.
AB  - BACKGROUND AND PURPOSE: An abundance of evidence suggests that interventions
      targeting fall risk factors are effective; however, it remains unknown whether,
      or to what extent, this body of evidence has affected the clinical practice of
      physical therapy providers. The purposes of this study were: (1) to describe
      knowledge of, and attitudes toward, fall risk factors and fall reduction
      strategies; (2) to assess self-reported use of fall reduction strategies with
      patients; and (3) to identify factors associated with increased use of fall
      reduction strategies with patients among physical therapy providers exposed to a
      behavioral change strategy. SUBJECTS AND METHODS: A cross-sectional survey of
      physical therapy providers from hospital-based and freestanding outpatient
      physical therapy facilities throughout north-central Connecticut was conducted
      between October 2002 and April 2003. The participants were 94 physical therapy
      providers who had been exposed to the Connecticut Collaboration for Fall
      Prevention (CCFP) behavioral change effort. The CCFP program uses multicomponent
      professional behavioral change strategies to embed fall risk factor assessment
      and management, based on evidence from randomized controlled trials, into the
      clinical care of older patients. A telephone questionnaire--focusing on fall risk
      factor knowledge and attitudes and self-reported fall risk factor assessment and
      management practices before and after exposure to the CCFP efforts--was
      administered to consenting physical therapy providers. RESULTS: Environmental
      hazards and gait and balance deficits were named as fall risk factors by 86 (91%)
      and 73 (78%) participants, respectively. All of the targeted risk factors were
      mentioned by at least 30% of the participants. Sixty-four participants (68%)
      reported increased fall reduction practice behaviors. The area of multiple
      medications was noted most frequently, with 77 participants (82%) noting new
      practices related to medication use. Only knowledge of fall risk factors and pre
      CCFP behaviors were associated with increased fall reduction practices.
      DISCUSSION AND CONCLUSION: Physical therapy providers reported an increase in
      practice behaviors in response to the multicomponent behavioral change strategy.
      Knowledge of fall risk factors was associated with increased fall reduction
      practice behaviors, most likely due to the focused nature of the education
      strategy.

PMID- 15842189
TI  - Decreased trunk angular displacement during sitting down: an early feature of
      aging.
AB  - BACKGROUND AND PURPOSE: Trunk motion plays an important role in achieving both
      sit-to-stand and stand-to-sit transfers. However, these 2 body transfers depend
      on different postural and mechanical constraints. Although the effects of aging
      on sit-to-stand transfers have been widely studied, there is a lack of
      information concerning stand-to-sit transfers. The aim of this study was to
      determine how angular displacements of the trunk and shank are affected by aging
      during sit-to-stand and stand-to-sit transfers. SUBJECTS: Ten community-dwelling
      older adults (mean age=75.9 years, SD=3.2) and 9 young adults (mean age=26.8
      years, SD=4.7) volunteered to participate. METHODS: Maximal angular displacements
      of the trunk and shank with respect to the vertical (ie, orientation angles) were
      measured, during standing up and sitting down, using an optoelectronic movement
      analyzer. RESULTS: For standing up, there was no difference between the young and
      older adults with regard to both maximal orientation angles. During sitting down,
      the maximal shank orientation angle was not affected by age, whereas the older
      adults had a smaller trunk motion compared with the young adults (approximately
      10 degrees less). DISCUSSION AND CONCLUSION: The results showed that older adults
      tended to minimize the forward body displacement during sitting down. This
      strategy could be seen as an adaptive mechanism to decrease the risk of anterior
      disequilibrium. The authors suggest that this feature could be used as an early
      marker of aging on postural control.

PMID- 15842190
TI  - Control of lead and trail limbs during obstacle crossing following stroke.
AB  - BACKGROUND AND PURPOSE: Obstacle crossing is compromised following stroke. The
      purpose of this study was to quantify modifications during obstacle clearance
      following stroke. SUBJECTS: Twelve subjects with stroke and 12 subjects without
      stroke participated in the study. METHODS: Kinematic variables were measured
      while participants crossed a 4-cm-high obstacle. Subjects with stroke walked at a
      self-selected speed; subjects without stroke walked at a comparable speed and at
      a self-selected speed. RESULTS: Several modifications were observed following
      stroke with both groups walking at self-selected speeds. The affected lead limb
      was positioned closer to the obstacle before crossing. Affected trail-limb
      clearance over the obstacle was reduced. Both affected and unaffected lead and
      trail limbs landed closer to the obstacle after clearance. Swing time was
      increased in the affected lead limb after obstacle clearance. Fewer modifications
      were detected at matched walking speed; the trail limb still landed closer to the
      obstacle. DISCUSSION AND CONCLUSION: Modifications during obstacle crossing
      following stroke may be partly related to walking speed. The findings raise
      issues of safety because people with stroke demonstrated reduced clearance of a 4
      cm obstacle and limb placement closer to the obstacle after clearance.

PMID- 15842191
TI  - Feasibility of electromyography-triggered neuromuscular stimulation as an adjunct
      to constraint-induced movement therapy.
AB  - BACKGROUND AND PURPOSE: The purpose of this case report is to explore the
      feasibility of electromyography-triggered neuromuscular stimulation (EMG-stim) as
      an adjunct to constraint-induced movement therapy (CIMT). CASE DESCRIPTION: The
      patient was a 72-year-old man, 10 years poststroke, who did not meet traditional
      CIMT criteria. The EMG-stim was applied to the wrist extensors of the patient's
      weaker arm for one half of the CIMT training hours. OUTCOMES: The intervention
      was feasible for this individual. Improvements were observed in motor behavior,
      quality and amount of use, muscle activity, wrist range of motion, and reaction
      time of the more-affected extremity. These improvements were paralleled by a
      change in the size and location of the extensor digitorum communis muscle
      representation in the primary motor cortex, as measured by transcranial magnetic
      stimulation mapping. DISCUSSION: These changes suggest that using EMG-stim as an
      adjunct to CIMT should be further investigated in individuals who have low
      functional abilities following stroke.

PMID- 15842192
TI  - Acrophobia and pathological height vertigo: indications for vestibular physical
      therapy?
AB  - BACKGROUND AND PURPOSE: Acrophobia (fear of heights) may be related to a high
      degree of height vertigo caused by visual dependence in the maintenance of
      standing balance. The purpose of this case report is to describe the use of
      vestibular physical therapy intervention following behavioral therapy to reduce a
      patient's visual dependence and height vertigo. CASE DESCRIPTION: Mr N was a 37
      year-old man with agoraphobia (fear of open spaces) that included symptoms of
      height phobia. Exposure to heights triggered symptoms of dizziness. Intervention.
      Mr N underwent 8 sessions of behavioral therapy that involved exposure to heights
      using a head-mounted virtual reality device. Subsequently, he underwent 8 weeks
      of physical therapy for an individualized vestibular physical therapy exercise
      program. OUTCOMES: After behavioral therapy, the patient demonstrated
      improvements on the behavioral avoidance test and the Illness Intrusiveness
      Rating Scale, but dizziness and body sway responses to moving visual scenes did
      not decrease. After physical therapy, his dizziness and sway responses decreased
      and his balance confidence increased. DISCUSSION: Symptoms of acrophobia and sway
      responses to full-field visual motion appeared to respond to vestibular physical
      therapy administered after completion of a course of behavioral therapy.
      Vestibular physical therapy may have a role in the management of height phobia
      related to excessive height vertigo.

PMID- 15842193
TI  - Potential adverse effects of statins on muscle.

PMID- 15842194
TI  - What will it take? The need for large-scale trials.

PMID- 15842197
TI  - Cystatins may confer viral resistance in plants by inhibition of a virus-induced
      cell death phenomenon in which cysteine proteinases are active: cloning and
      molecular characterization of a cDNA encoding cysteine-proteinase inhibitor
      (celostatin) from Celosia cristata (crested cock's comb).
AB  - Cystatins (cysteine proteinase inhibitors) have been recently used in plants as
      antiviral strategy against those viruses whose replication involves cysteine
      proteinase activity. We proposed an idea that cystatins may confer resistance by
      inhibition of a virus-induced cell-death phenomenon in which cysteine proteinases
      are active. To test this idea, a full-length cDNA library was constructed from
      the preflowering stage of Celosia cristata (crested cock's comb) leaves, and a
      cDNA clone with cystatin domain was isolated using an oligonucleotide probe
      designed on the basis of the conserved peptide of plant cystatins. It was
      expressed in an Escherichia coli expression system as a fusion protein. The
      purified recombinant product, termed 'celostatin' (Celosia cystatin), inhibited
      the enzymatic activity of papain indicating its cystatin activity and prevented
      TMV (tobacco mosaic virus)-induced hypersensitive-response cell death in
      Nicotiana glutinosa (a wild species of tobacco) leaves by 65-70% at the
      concentration of approx. 50 ng/ml. It also offered resistance against TMV and
      caused normal growth of the test plant. Since the activity of cysteine
      proteinases is not involved in the TMV replication process, we speculated that
      inhibition of the hypersensitive response by celostatin may be due to the
      inactivation of proteolysis involved in the plant cell death programme, a
      phenomenon that has already been reported in animal systems.

PMID- 15842198
TI  - PKB/AKT is involved in resumption of meiosis in mouse oocytes.
AB  - BACKGROUND INFORMATION: In fully grown mouse oocytes, a decrease in cAMP
      concentration precedes and is linked to CDK1 (cyclin-dependent kinase 1)
      activation. The molecular mechanism for this coupling, however, is not defined.
      PKB (protein kinase B, also called AKT) is implicated in CDK1 activation in lower
      species. During resumption of meiosis in starfish oocytes, MYT1, a negative
      regulator of CDK1, is phosphorylated by PKB in an inhibitory manner. It can imply
      that PKB is also involved in CDK1 activation in mammalian oocytes. RESULTS: We
      monitored activation of PKB and CDK1 during maturation of mouse oocytes. PKB
      phosphorylation and activation preceded GVBD (germinal vesicle breakdown) in
      oocytes maturing either in vitro or in vivo. Activation was transient and PKB
      activity was markedly reduced when virtually all of the oocytes had undergone
      GVBD. PKB activation was independent of CDK1 activity, because although
      butyrolactone I prevented CDK1 activation and GVBD, PKB was nevertheless
      transiently phosphorylated and activated. LY-294002, an inhibitor of
      phosphoinositide 3-kinase-PKB signalling, suppressed activation of PKB and CDK1
      as well as resumption of meiosis. OA (okadaic acid)-sensitive phosphatases are
      involved in PKB-activity regulation, because OA induced PKB hyperphosphorylation.
      During resumption of meiosis, PKB phosphorylated on Ser(473) is associated with
      nuclear membrane and centrosome, whereas PKB phosphorylated on Thr(308) is
      localized on centrosome only. CONCLUSIONS: The results of the present paper
      indicate that PKB is involved in CDK1 activation and resumption of meiosis in
      mouse oocytes. The presence of phosphorylated PKB on centrosome at the time of
      GVBD suggests its important role for an initial CDK1 activation.

PMID- 15842199
TI  - Can we diagnose, treat or even understand neurally mediated syncope?
AB  - There are significant gaps in our understanding of the pathophysiology, diagnosis
      and treatment of NMS (neurally mediated syncope). Contributions in this area will
      be welcomed by patients and physicians taking care of them alike. In this issue
      of Clinical Science, Simek and co-workers report a novel non-invasive
      physiological measurement that does not require head-up tilt to diagnose NMS.
      However, validation studies applied to an unselected patient population are
      needed before we can judge how useful this test will be in the diagnosis of NMS.

PMID- 15842200
TI  - Purification, characterization and molecular cloning of
      glycosylphosphatidylinositol-anchored arginine-specific ADP-ribosyltransferases
      from chicken.
AB  - Mono-ADP-ribosylation is a post-translational modification that regulates the
      functions of target proteins or peptides by attaching an ADP-ribose moiety. Here
      we report the purification, molecular cloning, characterization and tissue
      specific distribution of novel arginine-specific Arts (ADP-ribosyltransferases)
      from chicken. Arts were detected in various chicken tissues as GPI
      (glycosylphosphatidylinositol)-anchored forms, and purified from the lung
      membrane fraction. By molecular cloning based on the partial amino acid sequence
      using 5'- and 3'-RACE (rapid amplification of cDNA ends), two full-length cDNAs
      of chicken GPI-anchored Arts, cgArt1 (chicken GPI-anchored Art1) and cgArt2, were
      obtained. The cDNA of cgArt1 encoded a novel polypeptide of 298 amino acids which
      shows a high degree of identity with cgArt2 (82.9%), Art6.1 (50.2%) and rabbit
      Art1 (42.1%). In contrast, the nucleotide sequence of cgArt2 was identical with
      that of Art7 cloned previously from chicken erythroblasts. cgArt1 and cgArt2
      proteins expressed in DT40 cells were shown to be GPI-anchored Arts with a
      molecular mass of 45 kDa, and these Arts showed different enzymatic properties
      from the soluble chicken Art, Art6.1. RNase protection assays and real-time
      quantitative PCR revealed distinct expression patterns of the two Arts; cgArt1
      was expressed predominantly in the lung, spleen and bone marrow, followed by the
      heart, kidney and muscle, while cgArt2 was expressed only in the heart and
      skeletal muscle. Thus GPI-anchored Arts encoded by the genes cgArt1 and cgArt2
      are expressed extensively in chicken tissues. It may be worthwhile determining
      the functional roles of ADP-ribosylation in each tissue.

PMID- 15842201
TI  - Mapping leptin-interacting sites in recombinant leptin-binding domain (LBD)
      subcloned from chicken leptin receptor.
AB  - The binding domain of the chicken leptin receptor [chLBD (chicken leptin-binding
      domain)], subcloned from the full-size chicken leptin receptor and prepared in an
      Escherichia coli system, was subjected to site-directed mutagenesis to identify
      the amino acids involved in leptin binding. A total of 22 electrophoretically
      pure, >90% monomer-containing mutants were expressed, refolded and purified. The
      effects of the mutations were tested by the ability to form complexes with ovine
      leptin, and the kinetic parameters of interaction were determined by surface
      plasmon resonance. Six mutants were used to determine whether mutations of
      several amino acids that differ between chLBD and mammalian LBDs will affect
      affinity: none showed any such effect, except the mutant A105D (Ala(105)-->Asp),
      which exhibited some decrease in affinity. Surface plasmon resonance analysis
      identified six mutants in which binding activity was totally abolished (F73A,
      Y14A/F73A, V76A/F77A, L78A/L79A, V76A/F77A/L78A/L79A and A105D/D106V) and six
      mutants (Y14A, R41A, R41A/S42A/K43A, V103A, V135A/F136A and F136A) in which
      affinity for the hormone was reduced, mainly by increased dissociation rates. Gel
      filtration experiments indicated the formation of a 1:1 ovine or human leptin
      chLBD complex with a molecular mass of approx. 41 kDa. Gel-filtration experiments
      yielded 1:1 complexes with those mutants in which affinity had decreased, but not
      with the six mutants, which had totally lost their binding capacity. Modelling
      the leptin-chLBD complex indicated that the binding domain of the latter is
      located mainly in the L3 loop, which contributes nine amino acid residues
      interacting with leptin. Contact-surface analysis identified the residues having
      the highest contribution to the recognition site to be Phe73, Phe77 and Leu79.

PMID- 15842202
TI  - The Nordic Fertility Society.

PMID- 15842203
TI  - Survey of clinical practice: pre- and postoperative physiotherapy for pelvic
      surgery.
AB  - BACKGROUND: The objective of this survey was to obtain information about current
      physiotherapy practice for patients undergoing pelvic surgery. The aims were to
      evaluate whether differences exist in service provision between women's health
      physiotherapists (WHPTs) and hospital physiotherapists (HPTs) and in the
      guidelines used by physiotherapists to direct their service delivery. METHODS. A
      questionnaire was posted to the members of the Victorian Continence and Women's
      Health Physiotherapy Group (n = 130) and physiotherapists working in metropolitan
      and rural hospitals (n = 90). The questionnaire comprised questions relating to
      the aspects of treatment, including how referrals are made, funding,
      interventions provided and how they are delivered, and use of outcome measures.
      Data were summarized using descriptive statistics and Chi-square analysis of
      differences between WHPTs and HPTs. RESULTS: The response rate was 75.9%. In 67%
      of cases, service delivery was initiated by surgeon request, and most commonly
      for gynecologic patients (85%). Individual consultations were used on 96% of
      occasions and 8% were group sessions. Content of physiotherapy treatment for in
      patients varied, with WHPTs significantly more likely to prescribe pelvic floor
      muscle exercises (P = 0.003), bowel advice (P = 0.001), avoidance of risk
      activities (P = 0.002), and awareness of postoperative symptoms (P = 0.001).
      Conversely, HPTs were significantly more likely to perform respiratory checks (P
      = 0.002) and mobilization (P = 0.001). Eighty-seven percent of respondents
      regarded their service as suboptimal, citing the need for evidence to support the
      content and best timing of intervention. CONCLUSION: Differences exist in
      physiotherapy treatment for pelvic surgery patients. Further research is required
      to establish whether, and which, elements of physiotherapy intervention are
      effective.

PMID- 15842204
TI  - Maternal complications in women with chronic hypertension: a population-based
      cohort study.
AB  - BACKGROUND: The aim of the study was to determine if pregnant women with chronic
      hypertensive disease have an independent risk for preeclampsia, gestational
      diabetes or placental abruption. To examine if superimposed preeclampsia in this
      group of women is related to an increased risk of placental abruption. METHODS:
      This study is a population-based cohort study using the Swedish Medical Birth
      Register 1992-98. A population of 681 515 women aged between 15-44 years with
      singleton pregnancies, excluding women with systemic lupus erythematosus (SLE),
      diabetes mellitus and chronic renal disease were studied. Among these, 3374 women
      were diagnosed with chronic hypertensive disease. Multiple logistic regression
      analysis was performed and the outcome measures of crude and adjusted odds ratios
      (OR) were presented with 95% confidence intervals (CI). RESULTS: Chronic
      hypertensive disease is associated with multiparity, age, high body mass index
      and Nordic ethnicity. After controlling for confounders, chronic hypertensive
      disease is an independent risk factor for preeclampsia (OR 3.8; 95% CI 3.4-4.3),
      gestational diabetes (OR 1.8; 95% CI 1.4-2.4) and placental abruption (OR 2.3;
      95% CI 1.6-3.4). CONCLUSION: Chronic hypertensive disease is independently
      associated with an increased incidence of preeclampsia, gestational diabetes and
      placental abruption.

PMID- 15842205
TI  - Impact of rapid socio-economic changes on teenage pregnancies in Estonia during
      1992-2001.
AB  - BACKGROUND: Major socio-economic changes, including health care reforms and
      changes in the school curriculum, took place in Estonia after the country
      regained its independence in 1991. These changes affected people's reproductive
      behavior in many ways. In this article, the impact of the changes on the
      reproductive behavior of teenage girls, measured by adolescent fertility and
      abortion rates between 1992 and 2001, is analyzed. METHODS: National data on
      abortions and births were obtained from official medical statistics, particularly
      from the Estonian Abortion Registry and the Estonian Medical Birth Registry.
      Female population denominators for the age group 15-19 were obtained from the
      Statistical Office of Estonia. RESULTS: In teenagers, the birth rate decreased
      more than two times, from 49.7 per 1000 in 1992 to 23.8 per 1000 in 2001. The
      abortion rate per 1000 decreased from 55.5 in 1992 to 30.4 in 2001. Compared with
      all women of fertile age (15-49 years), at the beginning of the decade, teenagers
      decided more often to have a baby, and, at the end of the decade, they decided
      more often to terminate the pregnancy. Two-thirds of all pregnancies in teenagers
      end in abortion--either legally induced abortion (legal abortion and therapeutic
      abortion) or spontaneous abortion. In 2001, the abortion ratio was 116.4 among
      ethnic Estonians and 147.9 among non-Estonians. CONCLUSIONS: The case in Estonia
      again proves that the availability of information, contraceptives, services and
      education, and the existence of other goals in life besides childbearing, have an
      impact on teenage birth and abortion rates. Successful health promotion
      activities should take into consideration the differences in the reproductive
      behavior of different ethnic groups.

PMID- 15842206
TI  - Intensive management and early delivery reduce antenatal mortality in
      monoamniotic twin pregnancies.
AB  - BACKGROUND: Intensive management and elective delivery between 32 and 35 weeks of
      monoamniotic twin pregnancies were suggested as improving perinatal outcome. We
      sought to evaluate this management as viewed by the outcome of monoamniotic twin
      pregnancies in our population. METHODS: A retrospective systematic chart review
      of all monoamniotic twin pregnancies, diagnosed from January 1986 to June 2002,
      was performed in three medical centers. Demographics, pregnancy course, and
      perinatal outcome were evaluated. The management and outcome were compared
      between the group of survivors and the groups of intrauterine fetal demise (IUFD)
      and miscarriage. RESULTS: Thirty-three pairs of monoamniotic twins were
      identified. Excluded were three women, who chose to terminate the pregnancy.
      Total survival rate was 60% (of 60 fetuses, 36 were born alive, but one neonate
      died due to sepsis). None of the IUFD occurred in hospitalized patients, and two
      pairs of twins died after 32 weeks. In the 10 twin pairs who died in utero, cord
      entanglement was documented in eight (80%). There were two cases of twin
      discordance and two cases of twin-to-twin transfusion syndrome. One twin of the
      live-born group had congenital transposition of the great arteries. Furthermore,
      one of the hospitalized patients was delivered by means of an emergency cesarean
      section because of a non-reassuring non-stress test at 30 weeks. CONCLUSIONS:
      Women with monoamniotic twin pregnancies should be advised about the very high
      mortality and morbidity rate. Early diagnosis, close in-hospital antenatal
      surveillance starting at fetal viability, and elective delivery at 32 weeks would
      reduce the antenatal mortality.

PMID- 15842207
TI  - Childbirth and parenthood education classes in Sweden. Women's opinion and
      possible outcomes.
AB  - OBJECTIVE: To investigate first-time mothers' views about antenatal childbirth
      and parenthood education and their contact with other class participants after
      birth, and to compare participants and non-participants with respect to the use
      of pain relief, experience of pain, mode of delivery, childbirth overall,
      duration of breastfeeding, and assessment of parental skills. METHODS: A national
      cohort of 1197 Swedish-speaking women completed three questionnaires: during
      early pregnancy, 2 months, and 1 year after giving birth. RESULTS: Seventy-four
      percent of first-time mothers stated that antenatal education helped prepare them
      for childbirth, and 40% for early parenthood. One year after giving birth, 58% of
      the mothers had met with other class participants. These outcomes were associated
      with the number of class sessions. When controlling for the selection of women
      into participants and non-participants, no statistical differences were found
      concerning memory of labor pain, mode of delivery, overall birth experience,
      duration of breastfeeding, and assessment of parental skills. However,
      participants had a higher rate of epidural analgesia. Mothers who were young,
      single, with low level of education, living in a small city, and smokers were
      less likely to find the classes helpful. CONCLUSION: Participation in childbirth
      and parenthood education classes did not seem to affect first-time mothers'
      experience of childbirth and assessment of parental skills, but expanded their
      social network of new parents. The higher epidural rate suggests that
      participation in classes made women more aware of pain relief techniques
      available, rather than improving their own coping with pain. More research should
      focus on current forms of antenatal education, with special focus on women of low
      socioeconomic status.

PMID- 15842208
TI  - Surgical uterine devascularization for placenta accreta: immediate and long-term
      follow-up.
AB  - BACKGROUND: To report immediate and long-term outcome in patients with surgical
      uterine devascularization for placenta accreta. METHODS: Six patients with
      placenta accreta were treated conservatively during a cesarean section by a
      bilateral uterine and ovarian surgical devascularization procedure. Menstrual
      flow, imaging monitoring and further pregnancy were retrospectively reported.
      RESULTS: Blood transfusion was necessary in five cases and a hysterectomy was
      performed in one patient with placenta previa accreta. All patients resumed
      menstruation without oral contraception but one of them reported temporary
      clinical symptoms of estrogen insufficiency. A chronic placental retention
      occurred in three patients with incomplete placenta removal. One patient with
      both bilateral uterine and ovarian arterial ligations had a subsequent pregnancy
      complicated by a recurrent placenta accreta that was subsequently treated
      conservatively. CONCLUSIONS: Surgical uterine devascularization for placenta
      accreta may be useful for uterine conservation. However, reproductive capacity
      may be altered by placental chronic retention and further pregnancies may be
      complicated by recurrent placenta accreta.

PMID- 15842209
TI  - Cesarean section: is pretransfusion testing for red cell alloantibodies
      necessary?
AB  - BACKGROUND: Routine pretransfusion testing for red cell alloantibodies (RBCab) in
      cesarean patients is standard practice in many obstetric centers. The objective
      of the present study was to evaluate the usefulness of this test. METHOD: A
      retrospective study was conducted using computerized registers to extract data on
      blood transfusions and the occurrence of RBCab in cesarean patients. RESULTS: A
      total of 4434 admissions for cesarean section were identified. Only 10 patients
      (0.23%) had clinically significant RBCab, which had not been previously detected.
      Blood transfusions were required in relation to 147 cesarean sections (3.3%). A
      number of preoperative conditions, traditionally believed to be risk factors for
      preoperative and postpartum hemorrhage, occurred more frequently in transfused
      patients than in nontransfused. The probability of a cesarean patient having a
      previously undetected clinically significant RBCab and receiving a blood
      transfusion during admission for delivery was estimated to be 9.0 x 10(-5) (1 in
      11 050 cesarean sections). Analyses of the time relationships between cesarean
      sections and initiation of blood transfusions indicated that most often there
      would be enough time for postoperative antibody screening and/or cross matching
      if the routine pretransfusion testing was omitted. CONCLUSION: These findings
      suggest that routine pretransfusion testing in cesarean patients can be omitted.

PMID- 15842210
TI  - Emergency cesarean delivery in induction of labor: an evaluation of risk factors.
AB  - BACKGROUND: Induction of labor has been associated with an increased risk of
      emergency cesarean delivery. Knowledge of factors that influence the risk of
      cesarean delivery in women with induced labor is limited. METHODS: We performed a
      case-control study, nested within a population-based cohort of women with induced
      labor at term during 1991-1996 in Uppsala County, Sweden. Cases were women
      delivered with emergency cesarean delivery, and controls were women vaginally
      delivered (n = 193, respectively). Using logistic regression, analyses were
      performed. Odds ratio (OR) with 95% confidence intervals (CI) was used as a
      measure of relative risk. RESULTS: Women with a previous cesarean delivery had
      high risks of cesarean delivery (adjusted OR = 10.10, 95% CI = 3.30-30.92). The
      risk of cesarean delivery was also increased among nulliparous (adjusted OR =
      4.92, 95% CI = 2.81-8.61), short (adjusted OR = 2.20, 95% CI = 1.06-4.59), and
      obese women (adjusted OR = 2.03, 95% CI = 1.07-3.84). A cervix dilatation less
      than 1.5 cm doubled the risk of cesarean delivery (adjusted OR = 2.26, 95% CI =
      1.09-4.66). Mother's age, epidural analgesia, oxytocin augmentation, gestational
      age, and birthweight were not significantly associated with risks of cesarean
      delivery. CONCLUSIONS: Women with a previous cesarean delivery, nulliparous,
      short, and obese women with induced labor are at high risk of a cesarean
      delivery. When there is a need to deliver a woman with a previous cesarean
      section or a nulliparous woman with other risk factors for cesarean delivery, it
      may be prudent to consider an elective cesarean section.

PMID- 15842211
TI  - Genetics and assisted reproduction technology.
AB  - In the past 20 years, a significant improvement has been shown in the treatment
      for infertility in both women and men through the development of in vitro
      fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Only donated
      sperm could be previously used for treatment; now oocytes can also be donated.
      Furthermore, the combination of IVF and ICSI with advanced genetic methods has
      made preimplantation genetic diagnosis possible for many genetic conditions.
      These methods enable genetic testing of the early human embryo by using only a
      single cell, one blastomere biopsied from the embryo, as the sample from which
      the diagnosis of many chromosome rearrangements and other inherited diseases can
      be made. It has also been established that a considerable proportion of
      infertility is caused by genetic defects, which have several implications for
      infertility treatment. The purpose of this review is to give a concise
      introduction on how genetics is involved in assisted reproduction technology to
      specialists who may not be working in this particular field of gynecology, but
      who would need some knowledge of this for proper care of their patients.

PMID- 15842212
TI  - The effect of the phytoestrogen genistein and hormone replacement therapy on
      homocysteine and C-reactive protein level in postmenopausal women.
AB  - BACKGROUND: The aim of the study was to evaluate the effect, in postmenopausal
      women, of the phytoestrogen genistein and hormone replacement therapy (HRT) on
      circulating two independent factors of cardiovascular risk: homocysteine and C
      reactive protein (CRP). METHODS: Ninety healthy postmenopausal women, from 50 to
      60 years of age, were randomly assigned to receive genistein (n = 30; 54 mg/die)
      or continuous combined estrogen/progestin therapy (17-beta-estradiol 1 mg plus
      norethisterone acetate 0.5 mg) or placebo. Plasma homocysteine and serum CRP were
      measured at baseline and after 6 months of treatment. RESULTS: In the genistein
      group, plasma homocysteine and serum CRP showed no statistically significant
      difference from baseline (homocysteine: 11.36 +/- 0.39 micromol/l; CRP: 1.73 +/-
      0.31 mg/l) to 6 months treatment (homocysteine: 10.72 +/- 0.46 micromol/l; CRP:
      2.13 +/- 0.45 mg/l), without any significant difference versus the placebo group
      (homocysteine: 11.25 +/- 0.43 micromol/l; CRP: 1.74 +/- 0.22 mg/l). In the HRT
      group there was a slight, but not significant reduction, of plasma homocysteine
      mean value from baseline (11.21 +/- 0.44 micromol/l) to 6 months treatment (10.45
      +/- 0.38 micromol/l); whereas CRP mean value at the end of treatment (3.30 +/-
      0.55 mg/l) was significantly higher from baseline (1.61 +/- 0.25 mg/l) (P <
      0.01). However, after 6 months, no significant difference existed with the other
      two groups. CONCLUSIONS: The phytoestrogen genistein, after 6 months treatment,
      does not modify the independent cardiovascular risk linked to circulating
      homocysteine or CRP level. Our experience confirms critical increase of CRP serum
      level after HRT treatment, but not plasma homocysteine significant variation.

PMID- 15842213
TI  - Surgical and radiological management of uterine fibroids--a UK survey of current
      consultant practice.
AB  - BACKGROUND: The aim of this study was to determine the current surgical and
      radiological management of uterine fibroids by consultants working in the UK.
      METHODS: A structured questionnaire was posted to all 1439 UK consultants. Non
      responders were sent one reminder. The main outcome measures were surgical route
      and technique used for myomectomy, and the use and availability of uterine artery
      embolization (UAE). RESULTS: Eight hundred fifty-two (59%) consultants replied.
      Seven hundred thirty-five (86%) admitted to regular sessions of gynecologic
      surgery, and 75% of this group performed open myomectomy, 16% laparoscopic
      myomectomy, and 66% hysteroscopic myomectomy. Open myomectomy: Forty-one percent
      of consultants performed open surgery on uteri equivalent to 12-week gestational
      age or less, 87% prescribed preoperative gonadotrophin-releasing hormone agonists
      (GnRHa) in order to reduce surgical bleeding, with 35% using myomectomy clamps,
      23% tourniquets, and 19% vasoconstrictors. Laparoscopic myomectomy: The largest
      uterine size the majority would attempt was equivalent to a 12-week gestation,
      58.6% used preoperative GnRHa, 21% used intraoperative vasoconstrictors, and 1.4%
      tourniquets in order to minimize bleeding. Hysteroscopic myomectomy: As with
      laparoscopic myomectomy, the largest uterine size the majority would attempt was
      equivalent to a 12-week pregnancy. Blood transfusion: Twenty per cent, 10%, and
      7% reported the need for blood transfusion in up to 10% of patients undergoing
      open, laparoscopic, or hysteroscopic myomectomy, respectively. UAE: Fifty-one
      percent have access to UAE and 40% have referred at least one patient in 2001.
      CONCLUSIONS: Open and hysteroscopic myomectomy are frequently utilized in
      contrast to laparoscopic myomectomy. The reported rate of blood transfusion
      appears low. Although UAE is widely available, the majority of patients are still
      managed surgically.

PMID- 15842214
TI  - Screening for bacterial vaginosis in high-risk pregnancy: the experience of a
      developing country.

PMID- 15842215
TI  - Inadequate cervical smear: what do we do?

PMID- 15842216
TI  - Angle closure glaucoma induced by ritodrine.

PMID- 15842217
TI  - Postpartum maternal group B streptococcal meningitis.

PMID- 15842218
TI  - Colorectal cancer presenting with uncommon soft tissue invasion during pregnancy.

PMID- 15842219
TI  - Intramural pregnancy in a previous cesarean section scar: a case report on
      conservative surgery.

PMID- 15842220
TI  - Uchikova et al. Chondrosarcoma of the uterus. Acta Obstetrica et Gynecologica
      Scandinavica 2004; 83 (7): 686-8.

PMID- 15842221
TI  - Further decline in the incidence of eclampsia in Singapore.

PMID- 15842222
TI  - Postpartum hemorrhage from not very well-known vessels.

PMID- 15842226
TI  - Diagnosis of allergy syndromes: do symptoms always mean allergy?
AB  - Allergic disease has become a major burden in westernized societies because of a
      recent rise in its prevalence. Approximately one-third of children suffer from an
      allergic disease, with the prevalence varying from 15 to 20% for atopic
      dermatitis, 7 to 10% for asthma and 15 to 20% for allergic rhinitis and
      conjunctivitis. Despite the increase, it is important not to assume a diagnosis
      of allergy on the basis of symptoms alone, because allergic and nonallergic
      conditions may present with similar symptoms. An accurate allergy diagnosis is
      important in order to treat the patient most appropriately and to potentially
      prevent or delay the development of allergic disease. A good clinical history is
      the starting point for accurate allergy diagnosis but is not unequivocal. The
      European Academy of Allergy and Clinical Immunology has recognized the importance
      of allergy testing and therefore developed evidence-based recommendations on
      allergy testing in children. Widespread adherence to these recommendations should
      improve the quality of care for allergy patients. Cooperation between all
      healthcare professionals involved in the treatment of allergy patients is also a
      key to improve our response to the allergy epidemic.

PMID- 15842227
TI  - Allergy and infection: understanding their relationship.
AB  - Sensitization to indoor allergens has long been recognized as a risk factor for
      asthma and its associated phenotypes. Immunoglobulin E antibody quantification
      may be used to confirm that a particular sensitization has a role in the
      development of respiratory symptoms. However, in order to use quantitative
      information effectively, it is essential to understand the factors that
      contribute to the deterioration of symptoms and cause exacerbations. One such
      risk factor is high allergen exposure. Worsening asthma control is also
      associated with virus infections, in particular rhinovirus infection. Each of
      these factors in isolation is unlikely to have a major effect on symptoms.
      However, the combination of respiratory virus infection, allergen sensitization
      and concurrent high exposure to allergens markedly increases the risk for
      hospitalization. Further investigation of this synergism could help to understand
      the mechanisms of asthma exacerbations and lead to the development of strategies
      for prevention.

PMID- 15842228
TI  - When allergies complicate allergies.
AB  - The 'allergic march' is a term used to describe an individual's progress from one
      clinical manifestation of allergy to another, with age. Not all sensitized
      children will join the allergic march, but it appears that individuals who do not
      join the allergic march have a greater risk of displaying symptoms of allergic
      disease in adulthood. Consequently, there is a need for early diagnosis of
      allergy in children. Immunoglobulin E (IgE) antibody quantification is
      increasingly used for this purpose. However, rather than making a diagnosis based
      on single positive IgE antibody results only, it may be more efficient to test a
      profile of airborne and food allergens and use the sum of IgE antibody
      concentrations > or =3.5 kUA/l in combination with the number of allergens that
      elicit positive results tests. Allergic diseases often co-exist in patients, and
      the combination of several exposures at a given time (the allergen load) is
      related to disease severity. Therefore, a reduction of the allergen load is a key
      to successful treatment.

PMID- 15842229
TI  - Food allergy--accurately identifying clinical reactivity.
AB  - Up to 25% of adults believe that they or their children are afflicted with a food
      allergy. However, the actual prevalence of food allergy is much lower:
      approximately 6-8% of children suffer from food allergy during their first 3
      years of life, and many children then develop clinical tolerance. Food allergy
      encompasses a whole spectrum of disorders, with symptoms that may be cutaneous,
      gastrointestinal or respiratory in nature. Food disorders also differ according
      to the extent that they are immunoglobulin E (IgE)-mediated. Skin-prick testing
      is often used to identify food sensitization, although double-blind, placebo
      controlled food challenge (DBPCFC) tests remain the gold standard for diagnosis.
      Recent evidence suggests that quantitative IgE measurements can predict the
      outcome of DBPCFC tests and can replace about half of all oral food challenges.
      When an extensive medical history is obtained in combination with IgE
      quantification, even fewer patients may require formal food challenges. It has
      also become possible to map the IgE-binding regions of many major food allergens.
      This may help to identify children with persistent food allergy, as opposed to
      those who may develop clinical tolerance. In future, microarray technology may
      enable physicians to screen patients for a large number of food proteins and
      epitopes, using just a few drops of blood.

PMID- 15842230
TI  - Is the hygiene hypothesis still a viable explanation for the increased prevalence
      of asthma?
AB  - The hygiene hypothesis states that a reduced exposure to allergens in early life
      is solely implicated in the growing propensity for allergy sensitization.
      Important elements of the hypothesis include helminth infection, exposure to
      endotoxins, exposure to pets and growing up on a farm. However, the hygiene
      hypothesis alone does not provide an adequate explanation for the observed
      increase in allergic disease. For example, in North American inner cities, asthma
      is increasing among children who live in very poor housing, which might be
      assumed to be somewhat dirty. In order to explain the increase in asthma, we need
      to take a broader view and also consider alterations related to the adoption of a
      western lifestyle. It has been suggested that lifestyle changes related to
      obesity (e.g. a change in diet) are associated with asthma. Other changes include
      a progressive decrease in physical activity. This lifestyle factor seems to
      correlate best with the recent increase in asthma. Clearly, the link between
      physical activity and asthma needs to be investigated in more detail.

PMID- 15842231
TI  - Transcriptional activation of the oxytocin promoter by oestrogens uses a novel
      non-classical mechanism of oestrogen receptor action.
AB  - Transcriptional activation of the gene coding for the neuropeptide hormone
      oxytocin by oestrogens does not follow the classical model of oestrogen receptor
      action. The oxytocin promoter does not contain an oestrogen response element
      (ERE), but instead a high-affinity binding site for nuclear orphan receptors. In
      the present study, the oestrogen-dependent up-regulation of the bovine oxytocin
      promoter is investigated in MDA-MB 231 cells. Control by oestrogen is shown to be
      dependent on the integrity of the nuclear orphan receptor binding site and the
      presence of ligand-activated oestrogen receptor, but independent of oestrogen
      receptor binding to DNA. Partial agonists tamoxifen and raloxifen and the pure
      antagonist ICI 182 780 all show agonistic activities on transcription, while
      exhibiting normal binding affinities to oestrogen receptor (ER)alpha. Nuclear
      orphan receptors oestrogen receptor-related receptor alpha (ERRalpha) and germ
      cell nuclear factor (GCNF) are expressed to significant levels in MDA-MB 231
      cells. Binding of ERRalpha to the oxytocin promoter binding site can be
      demonstrated, suggesting the involvement of this nuclear orphan receptor in
      oestrogen-dependent up-regulation. The oestrogenic stimulation of the oxytocin
      promoter apparently is dependent on the stimulation of the transcriptional
      activity of this nuclear orphan receptor by ERK-1/ERK-2 mitogen-activated protein
      kinases (MAP kinases). This novel nonclassical mechanism of oestrogen action most
      probably is not restricted to the regulation of neuropeptide hormone expression,
      but may further contribute to the multitude of tissue-specific effects of
      oestrogenic substances.

PMID- 15842232
TI  - Expression of three gene families encoding cell-cell communication molecules in
      the prepubertal nonhuman primate hypothalamus.
AB  - Transsynaptic and glial-neuronal communication are important components of the
      mechanism underlying the pubertal activation of luteinizing hormone-releasing
      hormone (LHRH) secretion. The molecules required for the architectural
      organization of these cell-cell interactions have not been identified. We now
      show that the hypothalamus of the prepubertal female rhesus monkey expresses a
      multiplicity of genes encoding three families of adhesion/signalling proteins
      involved in the structural definition of both neurone-to-neurone and bi
      directional neurone-glia communication. These include the neurexin/neuroligin
      (NRX/NRL) and protocadherin-alpha (PCDHalpha) families of synaptic
      specifiers/adhesion molecules, and key components of the contactin-dependent
      neuronal-glial adhesiveness complex, including contactin/F3 itself, the contactin
      associated protein-1 (CASPR1), and the glial receptor protein tyrosine
      phosphatase beta. Prominently expressed among members of the NRX family is the
      neurexin isoform involved in the specification of glutamatergic synapses.
      Although NRXs, PCDHalphas and CASPR1 transcripts are mostly detected in neurones,
      the topography of expression appears different. NRX1 mRNA-containing neurones are
      scattered throughout the hypothalamus, PCDHalpha mRNA transcripts appear more
      abundant in neurones of the arcuate nucleus and periventricular region, and
      neurones positive for CASPR1 mRNA exhibit a particularly striking distribution
      pattern that delineates the hypothalamus. Examination of LHRH neurones, using the
      LHRH-secreting cell line GT1-7, showed that these cells contain transcripts
      encoding NRXs and one of their ligands (NRL1), at least one PCDHalpha (CNR
      8/PCDHalpha10), and the CASPR1/contactin complex. The results indicate that the
      prepubertal female monkey hypothalamus contains a plethora of adhesion/signalling
      molecules with different but complementary functions, and that an LHRH neuronal
      cell line expresses key components of this structural complex. The presence of
      such cell-cell communication machinery in the neuroendocrine brain suggests an
      integrated participation of their individual components in the central control of
      female sexual development.

PMID- 15842233
TI  - Central regulation of the hypothalamic-pituitary-adrenal axis during fetal
      development in the Guinea-pig.
AB  - We have previously shown that the foetal guinea-pig hypothalamic-pituitary
      adrenal (HPA) axis is activated near the time of parturition and that this is
      associated with changes in limbic glucocorticoid receptors (GR) and
      mineralocorticoid receptors. In the present study, we hypothesized that the
      foetal hypothalamic paraventricular nucleus (PVN) and pituitary contribute
      significantly to foetal HPA drive but that these areas remain sensitive to
      negative feedback by circulating glucocorticoids in late gestation. However, we
      observed decreased corticotrophin-releasing hormone mRNA expression in the PVN
      and decreased pro-opiomelanocortin (POMC) mRNA levels in the anterior pituitary
      with advanced gestational age. The reduction in POMC mRNA expression was likely
      the result of negative feedback via circulating glucocorticoids because GR mRNA
      was unchanged during development in the foetal pituitary. Furthermore, we found
      that maternally administered glucocorticoids significantly decreased foetal
      pituitary POMC mRNA expression in a dose-dependent manner at gestational day (gd)
      62 with male foetuses being more sensitive to these effects. These findings show
      that the foetal HPA axis remains highly sensitive to glucocorticoid feedback even
      as plasma adrenocorticotropic hormone and cortisol levels are elevated at the end
      of gestation.

PMID- 15842234
TI  - Expression of immediate early genes and vasopressin heteronuclear RNA in the
      paraventricular and supraoptic nuclei of rats after acute osmotic stimulus.
AB  - Monitoring the expression of immediate early genes (IEGs) is useful for following
      stress-induced cellular responses in the neuroendocrine system. We have examined
      the transcriptional activities of four IEGs (c-fos, junB, NGFI-A and NGFI-B) and
      of the arginine vasopressin (AVP) gene in the hypothalamic paraventicular (PVN)
      and supraoptic nuclei (SON) of rats after acute osmotic stimuli, using in situ
      hybridization histochemistry. After intraperitoneal (i.p.) administration of
      hypertonic saline (2% body weight, 900 mOsm/kg), the expression levels of all IEG
      mRNAs were increased significantly both in the PVN and SON at as early as 10 min,
      peaked at 30 min and remained elevated until 60 min. The expression of AVP
      heteronuclear (hn)RNA also peaked at 30 min, and remained elevated until 180 min.
      Thirty min after i.p. administration of hypertonic saline (600 mOsm/kg), the
      expression levels of all IEG mRNAs in the PVN and SON were significantly
      increased in comparison with those after i.p. administration of isotonic saline
      (290 mOsm/kg). Regression analysis revealed that expression levels of the IEG
      mRNAs and AVP hnRNA were positively correlated with the plasma concentration of
      sodium, and the rates of increase of the expression levels of all IEG mRNAs were
      similar. The expression levels of all IEG mRNAs examined are useful markers for
      following the changes of the AVP gene transcription in the PVN and SON after
      acute osmotic stimuli in rats.

PMID- 15842235
TI  - Search for neural substrates mediating inhibitory effects of oestrogen on
      pulsatile luteinising hormone-releasing hormone release in vivo in ovariectomized
      female rhesus monkeys (Macaca mulatta).
AB  - Neural substrates mediating the negative feedback effects of oestrogen on
      luteinising hormone-releasing hormone (LHRH) release were studied using the in
      vivo push-pull perfusion method in female rhesus monkeys. Twelve long-term
      ovariectomized female monkeys were implanted with Silastic capsules containing
      17beta-oestradiol 2 weeks before the experiments and, on the day of the
      experiment, oestradiol benzoate (EB, 50 microg/kg) or oil was subcutaneously
      injected. Push-pull perfusate samples from the stalk-median eminence were
      collected in 10-min fractions from 4 h before to 18-20 h after EB or oil
      injection. LHRH and neuropeptide Y (NPY) levels in the same perfusates were
      measured by radioimmunoassay, and glutamate and GABA in the same perfusates were
      assessed by high-performance liquid chromatography (HPLC). The results indicate
      that EB significantly suppressed LHRH release (P < 0.005) starting within 2 h
      after EB, and continued for 18 h or until the experiment was terminated. Pulse
      analysis suggested that oestrogen suppressed the pulse amplitude, but not pulse
      frequency, of LHRH release. By contrast, EB did not alter any parameters (mean
      release, pulse amplitude or frequency) of pulsatile NPY release throughout the
      experiment. HPLC analysis further suggested that neither glutamate nor GABA
      levels in the stalk-median eminence were changed with oestrogen-induced LHRH
      suppression. Oil treatment did not alter LHRH, NPY, GABA and glutamate levels. It
      is concluded that oestrogen induces suppression of pulsatile LHRH release within
      2 h, but the inhibitory effect of oestrogen on LHRH release does not appear to be
      mediated by NPY, GABAergic, or glutamatergic neurones.

PMID- 15842236
TI  - Activation of hypothalamic ATP-sensitive K+ channels by the aminoguanidine
      carboxylate BVT.12777.
AB  - Derivatives of 3-guanidinopropionic acid, such as leptin, reduce body weight in
      obese, diabetic mice. We have assessed whether one of these analogues, BVT.12777
      activates intracellular signalling pathways in the arcuate nucleus in a manner
      analogous to leptin and insulin. In addition, because these hormones have been
      shown to activate K(ATP) channels in a subset of arcuate neurones, we examined
      whether this channel is also a functional endpoint for BVT.12777 in the arcuate
      nucleus. BVT.12777 transiently increased phosphorylation of MAPK, STAT3, PKB and
      GSK3, in a manner identical to that observed for leptin and insulin. BVT.12777
      also hyperpolarized glucose-responsive neurones by increasing the activity of
      K(ATP) channels. The increase in K(ATP) activity driven by BVT.12777 was PI3
      kinase independent, unlike leptin and insulin activation of this channel, and
      could also be elicited in isolated patches. However, K(ATP) activity induced by
      BVT.12777 was dependent on actin filament dynamics, both in intact neurones and
      isolated patches. Thus, BVT.12777 modulates arcuate neurone K(ATP) activity by re
      organization of the cytoskeleton, a mechanism that has also been ascribed to
      leptin and insulin. Consequently, BVT.12777 appears to act as a leptin and
      insulin mimetic with respect to at least some elements of arcuate neurone
      intracellular signalling and the activation of K(ATP) channels. Resistance to
      leptin and insulin, associated with obesity has, at least in part, been
      postulated to be due to aberrant intracellular signalling in arcuate neurones.
      The data presented here indicate that it may be possible to develop drugs, which
      by-pass up-stream signalling components associated with adiposity hormone
      resistance, such as PI3-kinase, but can still induce functional outputs from
      arcuate neurones by targeting downstream components of the leptin and insulin
      signalling cascades.

PMID- 15842237
TI  - Sex differences in Fos protein expression in the neonatal rat brain.
AB  - Sex differences in the brain and behaviour are mostly a result of transient
      increases in testosterone during the perinatal period. Testosterone influences
      brain development primarily through aromatization to oestradiol and subsequent
      binding to oestrogen receptors. Although some studies report that steroid
      hormones regulate the expression of the inducible transcription factor, Fos, in
      developing brain, it is not known if there is a sex difference in Fos expression.
      Changes in Fos protein can be used as an indicator of neuronal/genomic activity.
      Thus, it provides a useful tool to identify brain regions responding directly or
      indirectly to steroid hormones. In a first experiment, we examined Fos protein
      expression in the developing male and female rat brain using western
      immunoblotting. Dissections were taken from male and female rat pups on the day
      of birth (postnatal day 0; PN 0), PN1, PN5, PN11 or PN20. Although there was no
      difference on PN 0, males expressed significantly greater levels of Fos protein
      on PN1, PN5 and PN20. In a second experiment, we localized the sex difference in
      Fos protein expression using immunocytochemistry. We found that males expressed
      significantly higher levels of Fos within a variety of brain regions. These data
      indicate a sex difference in Fos protein expression during brain development,
      suggesting a potential role for Fos in differentiating male from female rat
      brain.

PMID- 15842238
TI  - The comparison between pains, difficulties in function, and associating factors
      of patients in subtypes of temporomandibular disorders.
AB  - The aim of this study was to compare the multidimensional properties among
      subtypes of painful temporomandibular disorders (TMD): myofascial pain (group I),
      disc displacement (group II), arthralgia (group IIIa) and osteoarthritis (group
      IIIb). A total of 511 patients answered a battery of questionnaires, which
      included questions relating to intensity and duration of pain, the Japanese
      version of the McGill Pain Questionnaire, limitation of daily functions, the
      Hospital Anxiety and Depression Scale, the Eysenck Personality Questionnaire
      short-form and 34 items of behavioural contributing factors. Group IIIb showed
      significantly the highest age in all subtypes. Those in group I had higher
      depression scores than those in group II (P = 0.005). Group IIIa had a lower
      women's ratio than in group II (P = 0.001) and the patients showed a shorter pain
      duration than those in groups I (P = 0.000) and II (P = 0.001). Group IIIa
      patients also showed lower visual analogue scale (VAS) ratings for pain
      descriptors 'heavy' (P = 0.002) and 'tiring' (P = 0.004) than those of group I,
      and 'dull' (P = 0.005), 'heavy' (P = 0.001) and 'tiring' (P = 0.005) than those
      of group II. Group IIIa showed lower ratios of contributing factors of 'an
      awareness of grinding/clenching during sleep' (P = 0.000) and 'an awareness of
      clenching sensation when waking up at night' (P = 0.002) than those of group I,
      and also showed a higher ratio of 'a liking for a hard food' (P = 0.000) and
      lower ratio of 'talking for a long time on the telephone' (P = 0.001) than those
      of group II. In conclusion, although several properties were different between
      subtypes, the majority of them were similar in the four subtypes of TMD.

PMID- 15842239
TI  - Clinical and radiological follow-up results of patients with untreated TMJ closed
      lock.
AB  - The purpose of this study was to compare clinical and radiological findings of
      untreated closed lock patients at least 22 months after initial diagnosis. Ten
      patients with closed lock in at least one joint who had received no treatment
      were included in the study. Clinically maximum mouth opening, joint pain and
      joint sounds were recorded. Radiologically position of the disc, disc morphology,
      bone degeneration and presence of fluid were determined on magnetic resonance
      imaging. Clinical and radiological examinations were repeated 2-5 years after
      initial examinations. Results were statistically compared using either the non
      parametric McNemar test or the Wilcoxon signed-rank test. There were significant
      improvements in both mouth opening capacity and prevalence of joint pain, while
      no significant change in radiological examination. The results of this study
      suggested that closed lock patients undergo active adaptation in clinical
      symptoms.

PMID- 15842240
TI  - Condylar resorption during active orthodontic treatment and subsequent therapy:
      report of a special case dealing with iatrogenic TMD possibly related to
      orthodontic treatment.
AB  - A 28-year-old female underwent orthodontic treatment for approximately 22 months.
      During the later stages of this treatment, the patient reported right shoulder
      and neck-muscle pain. In addition, temporomandibular joint disorder (TMD) with a
      'clicking' sound during mastication commenced 5 months prior to treatment
      completion. Specific medication to deal with these symptoms was suggested by
      medical specialists, as were some stress-relief methods, although the pain still
      progressed, and subsequent clinical and radiographical examinations were
      undertaken by another orthodontist. Right mandibular condylar resorption was
      observed from both the panorex and temporomandibular joint (TMJ) radiographs. No
      clinical signs of rheumatic disease were observed, although bruxism was noted.
      Following the termination of the orthodontic treatment by the second
      practitioner, the patient was treated with splint therapy 1 month subsequent to
      which, the previous symptoms of pain in the shoulder and neck, and the clicking
      sound during mastication had subsided. During the 14-month period of splint
      therapy and follow-up, new bone growth in the right condyle was observed from
      radiographs.

PMID- 15842241
TI  - A metabolically active dermal replacement (Dermagraft) for vestibuloplasty.
AB  - This article describes the use of tissue-engineered dermal replacement in the
      vestibular extension instead of palatal donor tissue or (split-thickness) skin
      graft. In three patients the living human-derived fibroblast skin substitute
      (Dermagraft) was implanted on the wound surface after mucogingival junction and
      supraperiosteal dissection. Following application of Dermagraft, epithelial
      closure starting from the resection margins of the defect was observed, obviating
      further surgical treatment. Vestibular depth was increased and no scarring or
      frena occurred. Tissue-engineered dermal replacement consisting of living human
      fibroblasts appears to be a useful substitute for autogenous grafts in pre
      prosthetic surgery, offering the advantages of unlimited availability, good
      colour match and no donor site morbidity.

PMID- 15842242
TI  - A 5-year prospective study on small diameter screw-shaped oral implants.
AB  - Alveloar ridges of limited dimensions could preclude the placement of dental
      implants of the regular dimension. Smaller diameter implants - narrow platform
      (NP) implants were commercially available to address this issue. The aim of the
      study was to determine the 5-year clinical performance of 3.3 mm diameter NP
      implants. Twenty-three machined screw-shaped NP implants were placed in nine
      patients (six males; three females) between 18 and 70 years of age. Clinical and
      radiographic examinations were performed annually for 5 years. Recognized implant
      success criteria was used. The criteria were based on the mean marginal alveolar
      bone loss, the placement of prosthesis of satisfactory appearance, and the
      absence of implant mobility, peri-implant radiolucency, pain, discomfort or
      infection. One implant failed at abutment connection. The remaining 22 implants
      were restored and functioned successfully according to the criteria. The mean
      marginal alveolar bone loss during the first year was 0.41 +/- 0.17 mm. The mean
      marginal alveolar bone loss between the second and fifth year was 0.03 +/- 0.06
      mm. The success rate of NP implants according to a well-established set of
      criteria was 96%.

PMID- 15842243
TI  - An abutment screw loosening study of a Diamond Like Carbon-coated CP titanium
      implant.
AB  - The aim of this study was to quantify the extent of abutment screw loosening and
      thus understand the role of frictional and wear factors in abutment screw
      loosening by using a cyclic loading device to compare Diamond Like Carbon (DLC)
      coated and non-coated implants. The properties of DLC films, including hardness,
      wear resistance, chemical stability, and biocompatibility, are similar to those
      of real diamond materials. In this study, a 1-mum thick DLC film served to
      protect and lubricate a layer of commercially-pure titanium affixed to the top of
      a dental implant (external hexagon-shaped implant). A cyclic loading force was
      then applied to the top of the prosthetic portion of the implants in order to
      determine the difference in looseness of the titanium abutment screw between ten
      DLC-coated implants and ten non-coated implants. The abutment screw loosening
      tests were performed with 100 N of force at a frequency of 20 Hz. Data indicate
      that implants with a DLC coating are more resistant to an applied force (P =
      0.002) than are those without the coating. We hope these results will be useful
      for preventing implant abutment screw loosening.

PMID- 15842244
TI  - Static strength of molar region direct technique glass fibre-reinforced composite
      fixed partial dentures.
AB  - The aim of this study was to determine static fracture force of fibre-reinforced
      composite (FRC) fixed partial dentures (FPD) with different retainer designs. The
      fabrication simulated the process to make directly made 3-unit maxillary molar
      FPD. Four types of retainers were tested (n = 5): conventional crown preparation
      (1.2 mm axially and 2.0 mm occlusally), slot preparation (3.5 mm high x 3.5 mm
      wide x 1 mm deep), no preparation with broad fibre abutment contact, and
      combination of the slot and broad fibre contact were performed. The FPD contained
      unidirectional E-glass FRC veneered with particulate reinforced composite.
      Dimensions of the FPDs were homogenized. FPDs were stored at 1 week 37 degrees C
      deionized water, thermocycled between 5 degrees C and 55 degrees C (5000 cycles,
      dwell time 10 s) and statically loaded to failure. The slot retainer design
      yielded the lowest mean load to initial and final failure (FF) (1284 and 1313 N,
      respectively), the crown retainer the highest mean load to initial failure at
      1755 N, and the combination retainer resulted in the highest mean load to FF
      (1836 N) (anova, P < 0.001; Tukey multiple comparisons, 0.05 significance level).
      The results of this study suggest that the fabrication of direct FRC FPD does not
      necessarily require extensive preparation for the retainers.

PMID- 15842245
TI  - Colour stability of low fusing porcelains: an in vitro study.
AB  - Developing porcelain manufacturing technology provides lower fusing porcelains to
      avoid thermal stresses in metal substructure, particularly for titanium and gold
      alloys. So far, aesthetic properties of low fusing ceramics have not been well
      documented. The purpose of this study was, therefore, to estimate the long-term
      colour stability of low fusing ceramics by using an accelerated aging procedure.
      Four different ceramics (Vita Omega 900, Vita Titankeramik, Ceramco Finesse,
      Ceramco II) were used. Porcelain samples 11 +/- 0.5 mm in diameter and 1.4 +/-
      0.2 mm in thickness were prepared in three commonly used shades to provide 10
      samples of each group. The samples were fired in accordance with the
      recommendations of the manufacturers. CIE Lab readings were recorded with a
      spectrophotometer prior to experiments and after a 100 h accelerated aging. The
      results revealed that only Ceramco Finesse porcelain had a colour change (DeltaE
      > 1) that is noticeable by human eye. When the shades of porcelains were
      compared, C3 had greater colour change compared with A3 and B3 shades (P < 0.05).

PMID- 15842246
TI  - Influence of light intensity from different curing units upon composite
      temperature rise.
AB  - The unavoidable consequence of composite resin photopolymerization is temperature
      rise in tooth tissue. The temperature rise depends not only on the illumination
      time, but also on light intensity, distance of light guide tip from composite
      resin surface, composition and shade of composite resin and composite thickness.
      The most commonly used units for polymerization today are halogen curing units,
      which emit a large spectrum of wavelengths. A proportion of the spectrum has no
      influence on degree of conversion and therefore causes unnecessary temperature
      rise. Units based on light source - blue light emitting diodes (LED), as an
      alternative for halogen curing units, have been introduced in clinical practice.
      The aim of this study was to show the influence of the light intensity of curing
      units Elipar Trilight, Astralis 7 and Lux-o-Max unit on temperature rise in
      composite resin sample of Tetric Ceram. The temperature was measurement with
      Metex M-3850 D multimeter with the tip of temperature probe put into
      unpolymerized composite resin sample 1 mm depth. The highest temperature rise was
      recorded with standard curing mode for Elipar Trilight halogen curing unit (13.3
      +/- 1.21 degrees C after 40 s illumination), while the lowest temperature rise
      was recorded for the Lux-o-Max unit based on LED technology (5.2 +/- 1.92 degrees
      C after 40 s illumination).

PMID- 15842247
TI  - Antibacterial activity of glass-ionomer cements, compomers and resin composites:
      relationship between acidity and material setting phase.
AB  - Agar diffusion testing was used with four different media to evaluate the
      antibacterial activity of six products (one conventional glass-ionomer cement
      (GIC), two light-activated glass-ionomers, two polyacid-modified resin composites
      and one resin composite) on Streptoccoccus mutans. Their respective antibacterial
      activities were also compared during and after setting. The relationship between
      product acidity and antibacterial activity was evaluated. All the GICs
      demonstrated antibacterial properties in contrast to the polyacid-modified resin
      composites and resin composite which did not shown any antibacterial effects.
      Vitrebond GIC exhibited higher antibacterial action, probably because of a
      cytotoxic photo-initiator diphenyliodoniumchloride. A direct relationship between
      material acidity and growth inhibition of S. mutans was observed.

PMID- 15842248
TI  - Microleakage of glass-ionomer cement placed in association with non-setting
      calcium hydroxide.
AB  - The purpose of this investigation was to determine whether non-setting calcium
      hydroxide [Ca (OH)2] cement placed in the root canal system of premolar teeth
      would affect the subsequent microleakage of a glass-ionomer restoration (GIC).
      Following selection, 62 human premolar teeth extracted for orthodontic reasons
      were accessed and root canals prepared according to a standardized procedure. The
      specimens were then allocated randomly into two major groups each of 30 teeth.
      Two other teeth were used as a positive and a negative control. The control group
      was restored with glass-ionomer cement following drying of the canal and
      placement of a cotton wool pledget. The test group had all canals dressed with
      non-setting Ca(OH)2 and then was subdivided, one set (n = 22) being restored
      following conditioning of the access cavity margins, the other (n = 8) having the
      margins cleaned with a hand excavator. Samples were assessed for microleakage
      using a two-point scoring system (leakage or no leakage) in conjunction with a
      clearing technique using AgNO3. Using Fisher's exact test, a statistically
      significant difference was found between the control and test groups (P < 0.05)
      but there was no significant difference between the excavated and conditioned
      cavities (P=0.55). It is concluded that contamination of access cavity margins
      with Ca(OH)2 during medication of a root canal interferes with the bond of GIC,
      resulting in increased microleakage in vitro.

PMID- 15842249
TI  - Bio-sorption of acidic gelatine hydro-gels implanted in the back tissues of
      Fisher's rats.
AB  - Recent advance in tissue engineering therapy requires new scaffold materials.
      Acidic gelatine powders (10 wt%) were, thus, dissolved in water, were or were not
      cross-linked, and freeze-dried. After sterilization, prepared small sponges were
      implanted in 7-week-old Fisher's rats' subcutaneous tissues for up to 2 weeks.
      Sponges absorbed body fluid and changed into hydro-gels in vivo. Non-cross-linked
      hydro-gels were absorbed within 3 days, while cross-linked hydro-gels were
      eliminated after 7 days' implantation. Histological observations revealed that
      the common captivation process was mild while granulocytes and macrophages were
      encountered. Because acidic gelatine sponges can accommodate various basic growth
      factors, it can be speculated that prepared sponges might be used as short-time
      hydro-gel scaffolds and growth-factor carriers.

PMID- 15842250
TI  - Dental research in the context of general dental practice: can we get a 'bigger
      bang for the buck?'.

PMID- 15842251
TI  - Quantification of cell-cycle distribution and mitotic index in Hydra by flow
      cytometry.
AB  - The applicability of flow cytometry (FCM) to analyse cell-cycle distribution and
      mitotic cells in Hydra oligactis and Hydra vulgaris is demonstrated. The
      freshwater polyps H. vulgaris and H. oligactis are well-accepted animal models
      for studying cell proliferation, regeneration and differentiation. Disintegrated
      animals were labelled for FCM analysis according to the method of Nuesse et al.
      [(1990) Flow cytometric analysis of G(1) and G(2)/M-phase subpopulations in
      mammalian cell nuclei using side scatter and DNA content measurements. Cytometry
      11, 813]. Proliferation and regeneration experiments, in the absence or presence
      of the oligopeptide head activator, were quantified. Cell-cycle analysis of
      different parts of the animals shows low proliferation in the head region and
      high proliferation in the gastric and foot regions. Cell-cycle analysis of
      different parts of Hydra, comparison of H. oligactis and H. vulgaris, as well as
      pharmacological treatment, yielded results that are in agreement with prior
      microscopic analysis. Our results demonstrate that FCM is an appropriate
      technique for quantifying proliferation in this animal model. It can be used for
      basic research on development, regeneration and differentiation as well as for
      innovative drug investigation and toxicology studies.

PMID- 15842252
TI  - The effect of ZD1839 (Iressa), an epidermal growth factor receptor tyrosine
      kinase inhibitor, in combination with cisplatin, on apoptosis in SCC-15 cells.
AB  - The aim of this study was to determine the effect of ZD1839 on growth and
      apoptosis in SCC-15 (a human head and neck cancer cell line) lone, or in
      combination with cisplatin. High expression of the epidermal growth factor
      receptor has been implicated in the development of squamous cell carcinomas of
      head and neck. ZD1839 ('Iressa') is an orally active, selective epidermal growth
      factor receptor tyrosine kinase inhibitor that blocks signal transduction
      pathways implicated in proliferation and survival of cancer cells, and other host
      dependent processes promoting cancer growth. Here, growth arrest was observed
      with 3.64 microm ZD1839. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (sMTT) viability assay revealed a significant decrease (P < 0.001) in the
      percentage of surviving cells upon treatment with ZD1839 and cisplatin compared
      with cisplatin or ZD1839 on their own. Combined therapy of 3.64 microm ZD1839 for
      24 h, prior to administration of 100 microm cisplatin, significantly (P < 0.001)
      and additively increased the cytotoxicity effect of cisplatin. p53-independent
      apoptosis was seen with cisplatin treatment, a novel finding. These data support
      the use of ZD1839 in anti-cancer therapy, and particularly in combination
      therapy. Cisplatin may induce p53-independent apoptosis. Over-expression of Bcl-2
      in head and neck squamous cell carcinoma tumour cell lines is unlikely to be a
      general mechanism to protect these cells from apoptosis.

PMID- 15842253
TI  - Effects of the PKC inhibitor PD 406976 on cell cycle progression, proliferation,
      PKC isozymes and apoptosis in glioma and SVG-transformed glial cells.
AB  - It is well established that protein kinase C (PKC) isozymes are involved in the
      proliferation of glioma cells. However, reports differ on which PKC isozymes are
      responsible for glioma proliferation. As a means to further elucidate this, the
      objectives of our research were to determine how inhibition of PKC-alpha, PKC
      beta and PKCmu with PD 406976 regulates the cell cycle, cell proliferation and
      PKC during glioma growth and development. To establish the cell cycle effects of
      PD 406976 on brain cells (SVG, U-138MG and U-373MG glioma cells), specimens were
      treated with either dimethylsulfoxide (DMSO; control) or PD 406976 (2 microm).
      Results from flow cytometry demonstrated that PD 406976 delayed the entry DNA
      synthesis phase in SVG cells and delayed the number of cells entering and exiting
      the DNA synthesis phase in both U-138MG and U-373MG cells, indicating that PD
      406976 may inhibit G(1)/S and S phase progression. Assessment of cell viability
      demonstrated a cytostatic effect of PD 406976 on SVG, U-138MG and U-373MG glioma
      cell proliferation. The PD 406976-induced decreased proliferation was sustained
      at 48-96 h. A PKC activity assay was quantified and demonstrated that exposure of
      SVG and U-373MG glioma cells to PD 406976 suppressed PKC activity. Western
      blotting demonstrated reduced PKC-beta1, PKC-gamma and PKC-tau protein content in
      cells treated with PD 406976. We determined that the growth inhibitory effect of
      PD 406976 was not as a result of apoptosis.

PMID- 15842254
TI  - Cellular quiescence induced by contact inhibition or serum withdrawal in
      C3H10T1/2 cells.
AB  - Either confluence or serum withdrawal may cause growth arrest of cultured non
      transformed cells. Here, we compared sparsely populated and confluent C3H10T1/2
      cells with and without serum-containing medium. The following proliferation
      relevant end points were examined: cell-cycle distribution, Ki-67 antigen
      presence, the level of the von Hippel-Lindau (VHL) protein, and gene expression,
      determined using a microarray approach. In sparse/logarithmic cultures, the
      fraction of cells in G(0)/G(1) phase increased from 55 to 85% following serum
      withdrawal. Moreover, the fraction of Ki-67 positive cells dropped from 89 to
      47%. In confluent cultures, the majority of cells (80%) were in G(0)/G(1) phase
      and only 25-30% were Ki-67 positive, regardless of serum presence. In both serum
      deprived and contact-inhibited cultures, significant and distinct changes in gene
      expression were observed. Serum deprivation of sparsely cultured cells resulted
      in significant over-expression of several transcription factors, while confluent
      cells showed elevated expression of genes coding for Wnt6, uPar, Tdag51, Egr1,
      Ini1a and Mor1. These results indicate that contact inhibition and serum
      withdrawal lead to cellular quiescence through distinct genetic and molecular
      mechanisms.

PMID- 15842256
TI  - Healing of extraction sockets and surgically produced - augmented and non
      augmented - defects in the alveolar ridge. An experimental study in the dog.
AB  - OBJECTIVES: The current experiments had three aims (i) to determine whether the
      absence of the periodontal ligament (PDL) may alter features of the healing of an
      extraction socket, (ii) to examine if there were differences in the proportion of
      different tissues in resolved extraction sockets and surgically produced defects
      after 3 months of healing, (iii) to study the influence of different biomaterials
      on the healing of surgically produced bone defects. MATERIAL AND METHODS:
      Extraction sites: In five dogs, the 4th mandibular pre-molars were hemi-sected
      and the distal roots were removed. The extraction socket of one of the pre-molars
      was instrumented to eliminate all remnants of the PDL tissue. The socket of the
      contra-lateral pre-molar was left without instrumentation. The dogs were
      sacrificed after 3 months of healing. Defect sites: In five dogs, the pre-molars
      and 1st molars on both sides of the mandible were first removed and 3 months of
      healing allowed. After this interval three standardized cylindrical defects were
      prepared in each side of the mandible. The defects were 3.5 mm in diameter and 8
      mm deep. In each quadrant one defect was grafted with Bio-Oss Collagen, one with
      Collagen Sponge and one defect was left non-grafted. The dogs were sacrificed 3
      months after the grafting procedure. RESULTS: Extraction sites: The two
      categories of extraction sockets did not differ with respect to gross
      morphological features. The tissue of the extraction sites, apical of a newly
      formed bone bridge, was dominated by bone marrow. Few trabeculae of lamellar bone
      were also present. Defect sites: The non-augmented defect was sealed by a hard
      tissue bridge. In the central and apical portions of the defect bone marrow made
      up about 61%, and mineralized bone 39% of the tissues. The invagination of the
      surface of this crestal bone was 0.8+/-0.3 mm. The defect augmented with Collagen
      Sponge was covered by a hard-tissue bridge 38% of the tissue within the defect
      was made up of bone marrow while the remaining 62% was occupied by mineralized
      bone. The invagination of the hard-tissue bridge was on the average 0.6+/-0.1 mm.
      In defects augmented with Bio-Oss Collagen the biomaterial occupied a substantial
      portion of the tissue volume. Eighty-five percent of the periphery of the Bio-Oss
      particles were found to be in direct contact with newly formed mineralized bone.
      Woven bone and bone marrow made up 47% and 26% of the newly formed tissue. The
      invagination of the most coronal part of the bone defect was 0.1+/-0.1 mm.
      CONCLUSION: Sockets that following tooth removal had their PDL tissue removed
      exhibited similar features of healing after 3 months as sockets which had the PDL
      retained. The tissues present in an extraction site appeared to be more mature
      than those present in a surgically produced defect of similar dimension. The Bio
      Oss Collagen augmented defect exhibited less wound shrinkage than the non
      augmented defect.

PMID- 15842257
TI  - Experimental gingivitis in cigarette smokers: a clinical and microbiological
      study.
AB  - OBJECTIVE: To assess clinical and microbiological changes during experimental
      gingivitis in cigarette smokers and non-smokers. MATERIAL AND METHODS: Eleven
      current smokers (>/=5 years) and 11 (never-) non-smokers periodontally healthy or
      with gingivitis (PPD</=4 mm) were included. According to the original model (Loe
      et al. 1965), an experimental 3-week plaque accumulation period resulting in
      experimental gingivitis and a subsequent 2-week period of optimal plaque control
      were performed. Subgingival plaque samples were collected at days 0, 21 and 35
      from one site per quadrant, pooled and analysed using checkerboard DNA-DNA
      hybridization. RESULTS: Smokers {mean age: 24.7+/-2.2 [standard deviation (SD)]
      years, range 21-28 years} had a mean lifetime cigarette exposure of 6.4+/-2.8
      (SD) pack-years, while non-smokers presented with a mean age of 23.1+/-2.2 (SD)
      years (range 21-29 years). Between days 0, 21 and 35, no statistically
      significant differences in mean Plaque and mean Gingival Index scores were
      observed between smokers and non-smokers. In both smokers and non-smokers, mean
      total DNA probe counts did not significantly differ nor increase between days 0
      and 21. Also, between days 21 and 35 they did not significantly differ nor
      decrease. This was also true for the various proportions of bacterial complexes.
      CONCLUSION: Both current smokers and (never-) non-smokers reacted to experimental
      plaque accumulation with gingival inflammation. Periodontal and microbiological
      parameters assessed in current cigarette smokers did not significantly differ
      from those in non-smokers during an identical period of experimental plaque
      accumulation. Hence, the early host response to the bacterial challenge appears
      to be of similar magnitude and timing in both groups.

PMID- 15842258
TI  - Bone regeneration at implants with turned or rough surfaces in self-contained
      defects. An experimental study in the dog.
AB  - BACKGROUND: Marginal hard tissue defects present at implants with a rough surface
      can heal with a high degree of bone fill and osseointegration. The healing of
      similar defects adjacent to implants with a smooth surface appears to be less
      predictable. OBJECTIVE: The aim was to compare bone healing at implants with
      turned or rough surface topographies placed in self-contained defects using
      either a submerged or non-submerged installation technique. MATERIAL AND METHODS:
      Six dogs were used. Three months after tooth extraction four experimental sites
      were prepared for implant installation in both sides of the mandible. The
      marginal 5 mm of the canal prepared for the implant was widened. Thus, following
      implant placement a circumferential gap occurred between the bone tissue and the
      implant surface that was between 1 and 1.25 mm wide. In each side of the mandible
      two implants with a turned surface and two implants with a rough surface were
      installed. The implants in the right side were fully submerged, while a non
      submerged technique was applied in the left side. The animals were sacrificed 4
      months later, block biopsies of each implant site were dissected and ground as
      well as paraffin sections were prepared. RESULTS: The marginal defects around
      rough surface implants exhibited after 4 months of healing substantial bone fill
      and a high degree of osseointegration following either the submerged or the non
      submerged installation technique. Healing at turned implants was characterized by
      incomplete bone fill and the presence of a connective tissue zone between the
      implant and the newly formed bone. The distance between the implant margin (M)
      and the most coronal level of bone-to-implant contact (B) at implants with a
      rough surface was 0.84+/-0.37 mm at submerged and 0.90+/-0.39 mm at non-submerged
      sites. The distance M-B at implants with a turned surface was 3.39+/-0.52 mm at
      submerged and 3.23+/-0.68 mm at non-submerged sites. The differences between the
      rough and turned implants regarding the length of distance M-B were statistically
      significant (paired t-test). CONCLUSION: Osseointegration at implants placed in
      sites with marginal defects is influenced by the surface characteristics of the
      implant.

PMID- 15842259
TI  - Adjunctive effect of a polylactide/polyglycolide copolymer in the treatment of
      deep periodontal intra-osseous defects: a randomized clinical trial.
AB  - AIM: The aim of this study was to evaluate the clinical outcome of re
      constructive surgery in human deep intra-osseous defects with the use of a
      polylactide/polyglycolide (PLA/PGA) copolymer graft in conjunction with an open
      flap debridement (OFD) procedure (test group) as compared with OFD procedure
      alone (control group). MATERIALS AND METHODS: Thirty-two patients, each
      contributing one defect, were selected and completed the 12-month follow-up
      period. Sixteen patients (eight males, mean age: 49.9 years) received the test
      treatment, 16 patients (nine males, mean age: 42.8 years) received the control
      treatment. Clinical recordings, assessed at baseline, 6 and 12 months post
      surgery, included defect-specific plaque score, defect-specific bleeding score,
      probing depth (PD), clinical attachment level (CAL), and recession depth.
      Surgical procedure aimed to preserve supra-crestal soft tissues at defect site in
      order to ensure primary closure was used in all cases. RESULTS: Test and control
      treatment produced a significant CAL decrease and PD reduction at both 6 and 12
      months with respect to baseline value (p<0.000). At 6 months CAL was
      significantly greater in test compared with control group (p=0.019). Twelve-month
      CAL gain was 3.6+/-1.5 and 3.4+/-1.4 mm for the test and control group,
      respectively. At 12 months no significant differences in any of the clinical
      parameters were observed between groups. CONCLUSION: The results indicate that
      OFD with and without PLA/PGA graft provide clinically and statistically
      significant improvements in PD and CAL measurements. However, the additional use
      of PLA/PGA did not provide an additional benefit in terms of CAL gain and PD
      reduction compared with OFD procedure.

PMID- 15842260
TI  - Interleukin-1 levels in gingival crevicular fluid adjacent to restorations of
      calcium aluminate cement and resin composite.
AB  - OBJECTIVES: The aim of this clinical study was to intra-individually compare
      Class V restorations of a calcium aluminate cement (CAC), resin composite and
      enamel with respect to the adjacent levels of interleukin (IL)-1alpha, IL-1beta
      and IL-1 receptor antagonist (IL-1ra) in gingival crevicular fluid (GCF). The
      hypothesis was that there are higher IL-1 levels adjacent to resin composite,
      compared with CAC and enamel. MATERIALS AND METHODS: In 15 subjects, at least one
      set of two Class V restorations with subgingival margins, one CAC and one
      universal hybrid resin composite, and one control surface of enamel were
      included. In a cross-sectional study and on days 0, 3 and 7 of an experimental
      gingivitis study, GCFs were collected with Periopaper for 30 s. The GCF
      concentrations of IL-1alpha, IL-1beta and IL-1ra were quantified with enzyme
      linked immunosorbent assays. RESULTS: Neither the cross-sectional study nor the
      experimental gingivitis study showed any significant differences in the levels of
      IL-1alpha, IL-1beta and IL-1ra between CAC, resin composite and enamel sites
      (p>0.05). In the cross-sectional study, low IL-1 concentrations were observed.
      The IL-1 levels increased significantly during the experimental gingivitis.
      CONCLUSION: Regardless of CAC or resin composite, the restorations per se did not
      affect the GCF levels of IL-1 and IL-1ra, neither at healthy gingiva, nor at
      initiation of plaque-related gingival inflammation.

PMID- 15842261
TI  - Root surface removal and resultant surface texture with diamond-coated ultrasonic
      inserts: an in vitro and SEM study.
AB  - BACKGROUND: A new diamond-coated ultrasonic insert has been developed for scaling
      and root planing, and it was evaluated in vitro for the amount of root surface
      removed and the roughness of the residual root surface as a result of
      instrumentation. METHODS: 48 extracted single-rooted human teeth were ground flat
      on one root surface and mounted (flat side up) in PVC rings of standard height
      and diameter with improved dental stone. Each tooth surface was treated with
      either a plain ultrasonic insert (PI), an ultrasonic insert with a fine grit
      diamond coating (DI) or sharp Gracey curettes (HI). The mounted teeth were
      attached to a stepper motor which drove the teeth in a horizontal, reciprocal
      motion at a constant rate. The thickness from the flattened bottom of the ring to
      the flattened tooth surface was measured before and after 10, 20, and 30
      instrumentation strokes for each root surface with each of the experimental
      instruments. A number of treated teeth were randomly selected for examination
      with SEM and a profilometer. Statistical analysis (analysis of co-variance) was
      performed to compare the amounts of tooth structure removed among the 3
      instruments and t-test was used to compare the roughness of the treated root
      surfaces. RESULTS: The mean depth of root structure removed was PI 10.7 microm,
      HI 15.0 microm, and DI 46.2 microm after 10 strokes; and PI 21.6 microm, HI 33.2
      and DI 142.0 microm after 30 strokes, respectively. On average, 0.9 microm, 1.3
      microm, and 4.7 microm of root surface was removed with each stroke of PI, HI and
      DI, respectively. PI and HI were not different from each other for all the stroke
      cycles, while DI was significantly different from PI and HI for all the stroke
      cycles (p<0.0001). Analysis with the profilometer showed that the smoothest
      surface was produced by the PI followed by the HI. The DI produced a surface that
      was significantly rougher than the surface produced by the PI or HI. CONCLUSION:
      These results suggest that diamond-coated ultrasonic instruments will effectively
      plane roots, and that caution should be used during periodontal root planing
      procedures. Additionally, the diamond-coated instruments will produce a rougher
      surface than the plain inserts or the hand curettes.

PMID- 15842262
TI  - Association of the -159 CD14 gene polymorphism and lack of association of the 
      308 TNFA and Q551R IL-4RA polymorphisms with severe chronic periodontitis in
      Swedish Caucasians.
AB  - BACKGROUND: Severe forms of periodontitis are suggested to have a genetic basis.
      OBJECTIVE: The aim of the present investigation was to study the association of
      gene polymorphisms related to some immune regulation components (G-308A TNFA,
      Q551R IL-4RA and C-159T CD14) with severe chronic periodontitis. MATERIALS AND
      METHODS: Sixty patients (aged 36-74 years; mean 54.5+/-8.5) with severe and
      generalized chronic periodontitis were included. The patients exhibited bone loss
      >50% at all teeth. Thirty-nine periodontally healthy subjects between 35 and 78
      years of age (mean 51.0+/-10.9) were recruited as controls. DNA was isolated from
      peripheral blood cells and genotyping was performed by combination of PCR and
      restriction endonuclease mapping. RESULTS: While gene polymorphisms for TNFA and
      IL-4RA did not show any association with severe chronic periodontitis, the
      analysis of the -159 CD14 gene polymorphism revealed significant differences
      between test and control groups. The proportion of subjects that exhibited the TT
      genotype was significantly smaller in the group with severe periodontitis than in
      periodontal healthy group (p=0.028; Fisher's exact test). The C allele carriage
      was 90% in the periodontitis group and significantly higher than in the healthy
      control group (72%). CONCLUSION: It is suggested that the -159 CD14 gene
      polymorphism is associated with chronic periodontitis in Caucasian subjects of a
      north European origin.

PMID- 15842263
TI  - Clinical and radiographic performance of delayed-immediate single-tooth implant
      placement associated with peri-implant bone defects. A 2-year prospective,
      controlled, randomized follow-up report.
AB  - OBJECTIVES: The aim of the present study was to compare the delayed-immediate
      (Im) and the delayed (De) protocols for placement of single-tooth implants.
      MATERIAL AND METHODS: After allocation to the Im and De groups by random, 46
      patients were treated with a single-tooth implant with acid etched surfaces
      (Osseotite) in the anterior or pre-molar region of the maxilla or the mandible on
      average 10 days (Im) or 3 months (De) following tooth extraction, respectively.
      Forty-one patients attended a follow-up visit 2 years after implant placement
      corresponding to 1(1/2) years of loading of the implant restorations. Peri
      implant and prosthetic parameters were evaluated clinically and marginal bone
      levels measured on radiographs. RESULTS: Three implants were lost, all before
      mounting of the crown. None of the implant restorations had failed after 1(1/2)
      years of function. Probing pocket depths were reduced by up to 1.4 mm on average
      from the time of loading to the 2-year follow-up and at that time, no significant
      difference between the Im and De groups was found (4.2 versus 4.1 mm). A
      statistically significant radiographic marginal bone loss had occurred in the Im
      group (mean=0.8 mm) as well as in the De group (mean=0.7 mm) in the follow-up
      period. However, a mean marginal bone level of approx. 1.5 mm in both groups
      measured from the implant-abutment junction was found to be acceptable. It was
      demonstrated that probing pocket depths and marginal bone levels after 1(1/2)
      years of loading of the implant-retained crowns were not influenced by the
      presence of peri-implant bone defects immediately after implant placement.
      Furthermore, no severe prosthodontic complications, such as screw loosening or
      porcelain fractures, arose in this study material. CONCLUSION: High success rates
      of single-tooth implants after 1(1/2) years of function were achieved using the
      delayed-immediate and delayed implant placement techniques.

PMID- 15842264
TI  - Anxiety, gingival inflammation and periodontal disease in non-smokers and smokers
      - an epidemiological study.
AB  - OBJECTIVES: The aim of the present study was to investigate the influence of
      anxiety, measured by one single question, on gingival inflammation and
      periodontal disease in non-smokers and smokers. MATERIAL AND METHODS: The
      participants were 144 subjects with untreated periodontal disease 30-40 years of
      age, and 26 healthy controls, 30-40 years of age. All subjects were clinically
      examined and answered an uncomplicated question regarding anxiety in every day
      life, as well as smoking habits. The periodontitis subjects were divided into; an
      aggressive periodontitis (AP)-group and a chronic periodontitis (CP)-group.
      Fisher's exact probability t-test, analysis of variance (anova), Mann-Whitney U
      test and analysis of covariance (ancova) were used as statistical methods.
      RESULTS: Anxious subjects had a significantly higher gingival index than non
      anxious subjects, when controlling for smoking (p<0.01). The healthy anxious non
      smokers had an average score of GI 1.6 (+/-0.4 SD) compared with 1.2 (+/-0.4 SD),
      p<0.05 for the non-anxious non-smokers. Anxious smokers with periodontits (AP-/CP
      group) had significantly more sites with pockets >/=5 mm, compared with non
      anxious smokers, (p<0.05). CONCLUSIONS: The results of the present study, suggest
      that self-reported anxiety was associated with an adverse affect on the gingiva.
      Anxiety seemed to be associated with increased severity of periodontal disease in
      smokers.

PMID- 15842265
TI  - Clinical risk factors associated with incidence and progression of periodontal
      conditions in pregnant women.
AB  - OBJECTIVES: Few large studies have investigated the progression of periodontal
      conditions during pregnancy in a comprehensive manner. This study aimed to
      identify clinical factors that were predictive of incidence/progression of
      periodontal measures in pregnant women adjusting for relevant predictors.
      MATERIAL AND METHODS: Periodontal examinations were conducted on 891 pregnant
      women prior to 26 weeks gestational age and within 48 h after delivery.
      Gingivitis/periodontitis incidence/progression (GPIP) was defined as four plus
      sites with 2+ mm increase in probing depth (PD) that resulted in PD of at least 4
      mm at delivery. Multivariable models including relevant clinical variables and
      significant covariates were developed. RESULTS: While several clinical measures
      were significantly associated with the outcome, having >/=10% of sites with
      bleeding on probing (BOP) and four plus sites with PD >/=4 mm (PD4) were the best
      two predictors of GPIP (odds ratio (OR)=2.8, 95% confidence interval (CI)=1.8
      4.2; OR=2.0, 95% CI=1.4-2.9, respectively), adjusting for maternal race, age,
      enrollment weight, smoking during pregnancy, marital status, food stamp
      eligibility, and private health insurance. Multivariable models assessed the
      impact of BOP on the PD4-GPIP relationship. PD4 was significant in the presence
      of BOP (low BOP OR=1.3, 95% CI=0.5-3.3; high BOP OR=3.0, 95% CI=2.2-4.3).
      CONCLUSIONS: Enrollment BOP and PD4 were significant predictors of PD in pregnant
      women, however; PD4 is only a predictor with BOP.

PMID- 15842267
TI  - Implant therapy in partially edentulous, periodontally compromised patients: a
      review.
AB  - AIM: The purpose of the present study was to perform a review using a systematic
      approach to evaluate the long-term (>/=5 years) success of implants placed in
      partially edentulous patients with a history of periodontitis as evidenced by
      loss of supporting bone and implant loss. MATERIAL & METHODS: An electronic
      search of the National Library of Medicine, Washington DC (Medline-PubMed) was
      performed using specific search terms to identify studies assessing, in
      periodontitis patients, the success of implants with regard to bone level
      outcomes. Search was performed on abstracts registered up to October 2003.
      RESULTS: The searches identified 877 abstracts. Titles and abstracts were
      independently screened by two reviewers (G.A.W. & K.M.B.) to identify
      publications that met the inclusion criteria. Review of these abstracts resulted
      in 13 publications for detailed review. These papers were reviewed by the three
      authors. Finally four papers which met the criteria of eligibility were
      independently selected by the three reviewers. CONCLUSION: Based on the limited
      data, it seems justified to conclude that the outcome of implant therapy in
      periodontitis patients may be different compared to individuals without such a
      history as evidenced by loss of supporting bone and implant loss.

PMID- 15842266
TI  - The effect of a polyhexamethylene biguanide mouthrinse compared with a triclosan
      rinse and a chlorhexidine rinse on bacterial counts and 4-day plaque re-growth.
AB  - OBJECTIVES: For various clinical applications, polyhexamethylene biguanide
      hydrochloride (PHMB) has been used for many years as an antiseptic in medicine.
      Recently, a 0.04% and a 0.12% PHMB mouthwash were shown to inhibit plaque re
      growth and to reduce oral bacterial counts. In this study, a 0.2% PHMB mouthrinse
      (A) was compared with a positive control 0.12% aqueous chlorhexidine solution
      (B), a commercially available 0.3% triclosan/2.0% polyvinyl methyl ether maleic
      acid copolymer mouthrinse (Colgate Total Plax) (C), and a negative control
      placebo rinse (10% ethanol, flavour) (D). MATERIALS AND METHODS: The controlled
      clinical study was a double blind, randomized, four replicate cross - over
      design. Plaque re-growth was assessed with the Turesky et al. (1970) modification
      of the Quigley & Hein (1962) plaque index. The antibacterial effect was assessed
      by taking bacterial counts on the tooth surface (smears from the buccal surface
      of 16/26) and mucosa (smears from the buccal mucosa in opposite of area 16/26)
      after the professional prophylaxis and after the first rinse with the
      preparations on day 1 and prior to the clinical examination on day 5. Sixteen
      volunteers participated and, on day 1 of each study period were rendered plaque
      free, ceased toothcleaning, and rinsed twice daily with the allocated mouthrinse.
      On day 5, plaque was scored and smears were collected according to the protocol.
      A 10-day wash-out period was carried out between each rinse evaluation. Data were
      analysed using ancova with Bonferroni HSD adjustment for multiple comparisons
      (colony forming units per sample) with a significance level alpha=0.05. RESULTS:
      The 0.2% PHMB mouthrinse (A) was significantly better at inhibiting plaque than
      the placebo (D), but significant less effective than the 0.12% aqueous
      chlorhexidine solution (B). There is no significant difference between A and the
      0.3% triclosan/2.0% copolymer mouthrinse (C). Bacterial count reductions (tooth
      surface and mucosa) with PHMB (A) were significantly greater compared with the
      placebo (D) and triclosan (C), but significantly lower compared with
      chlorhexidine (B) (tooth surface) and equally effective compared with
      chlorhexidine (B) (mucosa). CONCLUSION: Consistent with previous studies, a PHMB
      mouthrinse was shown to inhibit plaque re-growth and to reduce oral bacterial
      counts, indicating that PHMB could be an alternative to established mouthrinses
      in preventive applications.

PMID- 15842268
TI  - Smoking, a weak predictor of periodontitis in older adults.
AB  - BACKGROUND: The impact of smoking habits on periodontal conditions in older
      subjects is poorly studied. AIMS: To assess if a history of smoking is associated
      with chronic periodontitis and medical history in older subjects. MATERIAL AND
      METHODS: The medical and dental history was collected from 1084 subjects 60-75
      years of age. Smoking history information was obtained from self-reports.
      Periodontal variables [clinical probing depth (PD)>/=5.0 mm, clinical attachment
      levels (CALs) >/=4.0 mm], and radiographic evidence of alveolar bone loss were
      assessed. RESULTS: 60.5% had never smoked (NS), 32.0% were former smokers (FS)
      (mean smoke years: 26.1 years, SD+/-13.1), and 7.5% were current smokers (CS)
      (mean smoke years 38.0 years, (SD+/-12.1). The proportional distribution of CAL
      >/=4.0 mm differed significantly by smoking status (NS and CS groups) (mean
      difference: 12.1%, 95% confidence interval (CI): 1.5-22.6, p<0.02). The Mantel
      Haenszel common odds ratio between smoking status (CS+FS) and periodontitis (>20%
      bone loss) was 1.3 (p<0.09, 95% CI: 0.9-2.0) and changed to 1.8 (p<0.02, 95% CI:
      1.3-2.7) with 30 years of smoking as cutoff. A weak correlation between number of
      years of smoking and CAL>/=4.0 mm was demonstrated (r(2) values 0.05 and 0.07)
      for FS and CS, respectively. Binary logistic forward (Wald) regression analysis
      demonstrated that the evidence of carotid calcification, current smoking status,
      gender (male), and the number of remaining teeth were explanatory to alveolar
      bone loss. CONCLUSIONS: A clinically significant impact on periodontal conditions
      may require 30 years of smoking or more. Tooth loss, radiographic evidence of
      carotid calcification, current smoking status, and male gender can predictably be
      associated with alveolar bone loss in older subjects.

PMID- 15842269
TI  - Coronally positioned flap procedures with or without a biodegradable membrane in
      the treatment of human gingival recession. A 6-year follow-up study.
AB  - BACKGROUND: Short-term data have indicated that treatment of gingival recession
      type defects by coronally positioned flap procedures with or without
      biodegradable membranes may result in similar treatment outcome. The aim of this
      study was to compare 12-month and 6-year follow-up results for these two
      treatment approaches. METHODS: Twenty patients with buccal bilateral Miller Class
      I or Class II gingival recession defects in cuspids or bicuspids were treated
      randomly by coronally positioned flap alone (20 sites) or in combination with a
      biodegradable membrane (20 sites). Clinical measurements at baseline, 6, 12
      months and 6 years included apical extent of gingival recession, width of the
      defect at the cemento-enamel junction (CEJ), width of keratinized tissue, as well
      as attachment level and probing depth. Eleven patients were available for the 6
      year evaluation. RESULTS: At 12 months (20 sites), both treatments resulted in
      significant gain of root coverage (p<0.001), stable probing depth, and increased
      attachment level (p<0.001). The 6-year evaluation (11 sites) showed a significant
      gain of root coverage for the non-membrane group only (p<0.05). No significant
      between-group differences were detected for any other treatment variable
      regardless of smoking status (p>0.05). Compared with baseline, the 6-year results
      showed that seven membrane sites gained root coverage, three were unchanged and
      one lost root coverage. For the 11 non-membrane sites, eight gained root
      coverage, and three were unchanged. The five membrane and the 10 non-membrane
      sites exhibiting complete root coverage at 6 months were reduced to two and one,
      respectively, at the 6-year evaluation. CONCLUSIONS: The coronally positioned
      flap procedure offers a simple and reliable treatment alternative as a root
      coverage procedure in Class I and Class II recession type defects. Placement of a
      biodegradable membrane underneath the flap does not seem to improve neither the
      short- nor the long-term results. Long-term outcome stability seems to be
      critically dependent on a continuous follow-up program with re-instruction in non
      traumatic brushing habits.

PMID- 15842270
TI  - Polymorphisms of the interleukin-18 gene in periodontitis patients.
AB  - BACKGROUND: Interleukin (IL)-18 regulates the expression of the proinflammatory
      cytokine interferon (IFN)-gamma. The present study sought to test the putative
      involvement of six different IL-18 gene polymorphisms in pre-disposition to
      destructive periodontal disease. METHODS: A total of 123 patients with
      periodontitis and 121 healthy controls were genotyped for six IL-18 polymorphisms
      at position -656, -607, -137, +113, +127 and codon 35/3. Genotyping has been
      performed by PCR and restriction fragment length polymorphism analysis. The
      frequencies of alleles and genotypes as well of haplotypes within both study
      groups were compared using the Pearson Chi-square test at a level of significance
      of 5% (p<0.05). RESULTS: Coseggregation was found to be 100% for the two
      polymorphisms at position -656 and -607 as well as for the polymorphisms at
      position -137, +113, and +127. The distribution of genotypes for the IL-18 gene
      polymorphism at position -656/-607 (p=0.854), at position -137/+113/+127
      (p=0.320), and at codon 35/3 (p=0.481) was not significantly different among
      periodontitis patients if compared with healthy control subjects. The
      distribution of haplotype combinations for the -607 and -137 polymorphism also
      showed not significant difference between the both study groups (p=0.545).
      CONCLUSION: Herein the six different IL-18 gene polymorphisms were not associated
      with destructive periodontal disease.

PMID- 15842271
TI  - Pain during prophylaxis treatment elicited by two power-driven instruments.
AB  - BACKGROUND: Sonic scalers have an elliptical and piezoceramic ultrasonic scalers
      a linear oscillation pattern. Thus, a sonic scaler "hammers" the tooth surface,
      irrespective of its alignment to the tooth, whereas a piezoceramic ultrasonic
      scaler may oscillate parallel to the tooth surface and gently remove calculus if
      the alignment is correct. The aim of this study was to measure pain on a visual
      analogue scale (VAS) during removal of supragingival calculus on mandibular
      incisors with a sonic or an ultrasonic scaler. MATERIAL AND METHODS: Seventy-four
      periodontally healthy subjects with supragingival calculus on the mandibular
      incisors were treated with both a sonic and a piezoceramic ultrasonic scaler in a
      split-mouth design. The sequence of instrument application and allocation of
      instruments to jaw side were randomized. Patient comfort was assessed with a VAS
      after treatment. RESULTS: The VAS results did not show any difference between the
      two instrumentation modalities. CONCLUSION: For calculus removal during
      prophylaxis the type of power-driven instrument does not seem to have an impact
      on perceived pain. This means that the oscillation pattern does not influence the
      pain experience.

PMID- 15842273
TI  - Using group-sequential analysis to achieve the optimal sample size.

PMID- 15842274
TI  - The tension-free vaginal tape reviewed: an evidence-based review from inception
      to current status.

PMID- 15842275
TI  - Misoprostol to treat postpartum haemorrhage: a systematic review.

PMID- 15842276
TI  - Prenatal diagnosis and obstetric outcomes in triplet pregnancies in relation to
      chorionicity.
AB  - OBJECTIVE: This study describes the frequency, pregnancy complications and
      outcomes of non-trichorionic triplet pregnancies. DESIGN: A retrospective
      observational study. SETTING: Two tertiary level referral centres of Obstetrics
      and Prenatal Medicine, Germany. POPULATION: All women booked to receive targeted
      ultrasound screening between January 1998 and June 2003. The mixed low and high
      risk population included 36,430 women with ultrasound examinations between 11 and
      24 weeks of gestation. Of those with available outcome, 176 were triplet
      pregnancies with three viable fetuses. METHODS: Analysis of ultrasound data and
      perinatal outcome in triplet gestations who had first and second trimester
      targeted ultrasound examination. Pregnancies with monochorionic or dichorionic
      placentation were identified and pregnancy outcome was compared to trichorionic
      triplets. MAIN OUTCOME MEASURES: Intrauterine fetal death, fetal growth
      restriction (FGR), mean discordance and survival rate in non-trichorionic versus
      trichorionic triplets. RESULTS: Triplets were trichorionic in 81.8% and had a
      monochorionic or dichorionic placentation in the remaining 18.2%. The rate of
      monochorionicity and dichorionicity was significantly higher after spontaneous
      conception than after assisted reproductive technologies (44.8%vs 12.9%, P <
      0.001). In non-reduced monochorionic and dichorionic triplets compared with non
      reduced trichorionic triplets, there was a higher rate of intrauterine fetal
      death (8.8%vs 1.5%, P < 0.01), FGR (33.3%vs 25.5%), mean discordance (20.5%vs
      12.7%, P < 0.01), discordance >30% (26.3%vs 2.9%, P < 0.01) and delivery <32
      weeks of gestations (47.4%vs 32.2%). There was a lower survival rate in non
      trichorionic triplets (84.2%) than in trichorionic ones (91.7%). CONCLUSION:
      Triplet pregnancies with a monochorionic or dichorionic placentation are at
      significantly higher risk of adverse pregnancy outcome compared with trichorionic
      pregnancies. First trimester evaluation of chorionicity is strongly emphasised.

PMID- 15842277
TI  - A randomised controlled trial of biopsy forceps and cannula aspiration for
      transcervical chorionic villus sampling.
AB  - OBJECTIVE: This trial compared two instruments for transcervical chorionic villus
      sampling (CVS). DESIGN: Randomised controlled trial. SETTING: Regional university
      prenatal diagnosis and treatment centre. POPULATION: Two hundred women were
      randomised at 10(+0)-12(+6) weeks of gestation to transcervical CVS using cannula
      aspiration (CA) or biopsy forceps (BF). METHODS: Women undergoing indicated CVS
      signed informed consent. Randomisation after decision to perform transcervical
      CVS. MAIN OUTCOME MEASURES:  PRIMARY OUTCOME: the rise in maternal serum alpha
      fetoprotein (alpha-FP). SECONDARY OUTCOMES: (i) placental trauma (fetomaternal
      haemorrhage [FMH]); (ii) laboratory, procedure, and cytogenetic results and
      pregnancy outcomes; (iii) patient and operator satisfaction; and (iv) economic
      analyses. Analyses were performed by intention to treat. RESULTS: The -FP rise
      did not differ between groups; there was no other evidence of placental trauma.
      BF were better tolerated by women, provided culturable tissue, after fewer
      instrument passes, with greater ease and in less time. BF were associated with
      cost savings. CONCLUSIONS: Unlike -FP, other markers of FMH were unaltered,
      questioning the reliability of alpha-FP as an indicator of FMH. Compared with CA,
      transcervical BF caused comparable placental trauma, appeared to be similarly
      effective and safe and were preferred by operators and patients.

PMID- 15842278
TI  - Prediction of congenital toxoplasmosis by polymerase chain reaction analysis of
      amniotic fluid.
AB  - OBJECTIVE: To determine the accuracy of polymerase chain reaction (PCR) analysis
      of amniotic fluid for fetal toxoplasmosis according to clinical predictors of
      outcome and study centre. DESIGN: Prospective cohort study. SETTING: Nine
      European centres. POPULATION: Women with suspected toxoplasma infection
      identified by prenatal screening. METHODS: Logistic regression was used to
      examine the effects of gestational age at maternal seroconversion, treatment and
      timing of amniocentesis, on PCR accuracy, and to calculate the post-test
      probability of congenital toxoplasmosis. MAIN OUTCOME MEASURES: Infants had
      congenital toxoplasmosis if specific IgG persisted beyond 11.5 months. Uninfected
      infants had undetectable IgG in the absence of anti-toxoplasma treatment.
      RESULTS: Of 593 PCR results, 64 were positive (57 confirmed infected), and 529
      were negative (23 confirmed infected). The likelihood ratio for a positive PCR
      result decreased significantly with trimester at seroconversion, but did not
      change significantly for a negative result. Weak associations were detected
      between sensitivity and, inversely, with specificity, and gestational age at
      maternal seroconversion. There was no significant association between sensitivity
      and centre, type or duration of treatment, or timing of amniocentesis.
      Specificity differed significantly between centres (P < 0.001). The change in pre
      to post-test probability of infection was maximal for a positive PCR after first
      trimester seroconversion, affecting 1% of women tested, and a negative PCR after
      third trimester seroconversion, affecting half the women tested. CONCLUSIONS:
      Prediction of the risk of congenital toxoplasmosis should combine estimates of
      test accuracy and maternal-fetal transmission, which take account of the
      gestational age at which the mother seroconverted. Local laboratory standards
      will affect the generalisability of these results.

PMID- 15842279
TI  - Cystatin-C and beta trace protein as markers of renal function in pregnancy.
AB  - OBJECTIVE: To assess the validity of Cystatin-C (Cys-C) and beta trace protein
      (BTP) as clinical markers of glomerular filtration rate (GFR) in pregnant women.
      DESIGN: Prospective cross sectional study. SETTING: Obstetric unit of a tertiary
      care hospital. POPULATION: One hundred and thirty-seven normal pregnant women and
      13 women postpartum. METHODS: Twenty-four hour creatinine clearance (CrCl), serum
      creatinine, Cys-C and BTP concentrations were measured on normal pregnant women
      in the first trimester (n= 5), second trimester (n= 68) and third trimester (n=
      64) and in 13 women postpartum. Data are given as median (2.5th centile, 97.5th
      centile). MAIN OUTCOME MEASURES: Serum concentrations of Cys-C and BTP compared
      with creatinine clearance and serum creatinine. RESULTS: The median serum
      creatinine throughout gestation was 53 micromol/L (39, 71), and median CrCl was
      143 mL/minute (91 to 216). Postpartum, creatinine rose to 74 micromol/L (58, 86)
      and CrCl decreased to 104 mL/minute (71, 159). For Cys-C, the median
      concentration was 0.70 mg/L (0.46, 1.32), and 0.54 mg/L (0.36, 0.96) for BTP.
      Comparing the second and third trimesters, there was no significant difference
      between CrCl (median 145 vs 141 mL/minute) and BTP concentrations (median 0.51 vs
      0.55 mg/L), while median Cys-C was significantly higher in the third trimester
      (0.61 vs 0.88 mg/L; P < 0.001). Unlike creatinine and BTP, Cys-C levels decreased
      to 0.72 mg/L (0.57, 0.95) postpartum. The only significant relationship of either
      of these markers to the standard used for GFR was between Cys-C and CrCl in the
      third trimester, and the correlation was weak (r= 0.27 for 1/Cys-C vs CrCl).
      CONCLUSION: These data demonstrate that despite claims to the contrary, Cys-C is
      a poor marker of GFR during pregnancy. Similarly, BTP shows little promise.

PMID- 15842280
TI  - The oral direct thrombin inhibitor, ximelagatran, an alternative for
      anticoagulant treatment during the puerperium and lactation.
AB  - OBJECTIVE: To determine the excretion of the oral direct thrombin inhibitor (oral
      DTI), ximelagatran, and its active form, melagatran, in human milk, and to thus
      evaluate the potential exposure of breastfed infants to melagatran. DESIGN: An
      open, single dose, single centre study. SETTING: Department of Antenatal Care,
      Primary Health Care South Bohuslan and Institute for the Health of Women and
      Children, Goteborg University, Sweden. SAMPLE: Seven healthy Caucasian
      breastfeeding women who were at least two months postpartum were studied.
      METHODS: The concentrations of ximelagatran, its two intermediates, and
      melagatran were determined using liquid chromatography-mass spectrometry, with
      the limit of quantification of 2 nmol L(-1) for human milk and 10 nmol L(-1) for
      plasma concentrations. MAIN OUTCOME MEASURES: Concentrations of ximelagatran, its
      intermediates and melagatran were measured in breast milk over 72 hours, and in
      plasma over 12 hours, after a single oral 36 mg dose of ximelagatran. RESULTS:
      Neither ximelagatran nor its intermediates were detected in human breast milk.
      Only trace amounts of melagatran were detected. The mean cumulative amount of
      melagatran excreted into breast milk over the 72-hour period after dosing with
      oral ximelagatran was 0.00091% of the administered dose of ximelagatran.
      Ximelagatran was well tolerated, with no clinically relevant changes in
      laboratory variables or vital signs. CONCLUSIONS: Trace levels of melagatran are
      excreted in human breast milk following administration of the oral DTI
      ximelagatran. The exposure of breastfed infants to melagatran appears to be low
      and is therefore unlikely to be of clinical concern.

PMID- 15842281
TI  - Increased fetal RhD gene in the maternal circulation in early pregnancy is
      associated with an increased risk of pre-eclampsia.
AB  - OBJECTIVE: To determine whether the fetal RhD gene is present in the maternal
      circulation in early pregnancy prior to the clinical manifestation of pre
      eclampsia. DESIGN: This is a nested case-control study. SETTING: Blood samples
      were obtained from patients attending for a first antenatal visit. SAMPLE: Cases
      were asymptomatic RhD negative women (n= 23) who subsequently developed pre
      eclampsia matched to RhD negative controls (n= 23) for parity and gestational
      age. METHODS: Real time PCR using TaqMan primers and probes directed against the
      RhD gene quantified fetal DNA in the maternal circulation. MAIN OUTCOME MEASURES:
      Quantity of RhD gene detected. RESULTS: As the copy number of RhD gene per
      millilitre of whole blood at 15 weeks of gestation increased, there was a
      significantly increased risk of developing pre-eclampsia. There was a graded
      association between copy number of RhD gene in early pregnancy and severity of
      disease with controls having 6942, mild pre-eclamptics 83,273 and severe pre
      eclamptics 285,793 copies/mL (logscale 3.6, 4.0 and 4.5, respectively).
      CONCLUSION: Increased fetal RhD gene is present in the maternal circulation in
      early pregnancy in women who subsequently develop pre-eclampsia and there appears
      to be a graded response between the quantity of fetal DNA and severity of pre
      eclampsia.

PMID- 15842282
TI  - Antioxidants and preterm prelabour rupture of the membranes.
AB  - OBJECTIVE: To investigate the relationships of dietary intakes and serum levels
      of antioxidant nutrients to the risk of prelabour rupture of the membranes
      preterm (PPROM). DESIGN: A prospective observational cohort study. SETTING: A
      district general hospital in the south of England. POPULATION: Eight hundred and
      twelve white nulliparous women with singleton pregnancies. METHODS: Serum
      antioxidant concentrations and dietary intakes were measured in the second
      trimester. Associations with the risk of PPROM were investigated. MAIN OUTCOME
      MEASURE: Preterm prelabour rupture of the membranes. RESULT: Serum concentrations
      of the antioxidant lutein, but no other nutrient, was associated with the risk of
      PPROM. Maternal smoke exposure (serum cotinine) also predicted PPROM. Women with
      high serum lutein concentrations (top third) in early pregnancy had four times
      greater risk than women in the lowest third (95% CI 1.3-11.9; P= 0.009) after
      adjusting for smoke exposure. Similar results were obtained using lutein levels
      from later pregnancy. CONCLUSION: We found no evidence that antioxidant nutrients
      are protective against PPROM. Rather, high levels of lutein were associated with
      an increased risk.

PMID- 15842283
TI  - DNA identification of fetal cells isolated from cervical mucus: potential for
      early non-invasive prenatal diagnosis.
AB  - OBJECTIVES: To develop a reliable method to isolate fetal cells for genetic
      diagnosis. DESIGN: Aspiration of cervical mucus from pregnant women in the first
      trimester. SETTING: Pregnant women were recruited before an elective termination
      of pregnancy. POPULATION: Sixty pregnant women (7-10 weeks of gestation).
      METHODS: Fetal cells were isolated from aspirated cervical mucus of pregnant
      women using a combination of enzymatic digestion, fluorescent
      immunohistochemistry, micromanipulation and single-cell DNA allelic profiling.
      MAIN OUTCOME MEASURES: The isolation and identification of fetal cells. RESULTS:
      The transformation of the tenacious cervical mucus into a single-cell suspension
      enabled the isolation and identification of fetal cells by fluorescent
      immunohistochemistry. Confirmation of fetal origin was accomplished by single
      cell DNA allelic profiling alongside known maternal cells. CONCLUSIONS: This
      novel non-invasive method is rapid and efficient with results attainable within
      24 hours as early as seven weeks of gestation. The technique would offer earlier
      reassurance and the option of first trimester therapeutic abortions to both high
      and low risk pregnant women.

PMID- 15842284
TI  - The natural history of white coat hypertension during pregnancy.
AB  - OBJECTIVE: White coat hypertension (WCH) is a common phenomenon with a long term
      prognosis intermediate between those with true hypertension and true
      normotension. The natural history of this phenomenon throughout pregnancy remains
      unknown. We assessed the likelihood of women with an initial diagnosis of WCH
      developing pre-eclampsia (PE) as their pregnancy progressed. DESIGN: Prospective
      observational study. SETTING: St George Hospital, a teaching and University
      hospital. POPULATION: Two hundred and forty-one pregnant women with an early
      pregnancy diagnosis of essential hypertension (EH). METHODS: Eighty-six women had
      this diagnosis (EH) confirmed pre-pregnancy by 24-hour ambulatory blood pressure
      monitoring (ABPM) or repeated automated home blood pressure (BP) self
      measurement. The remaining 155 underwent 24-hour ABPM in early pregnancy to
      establish their diagnosis. Women found to have WCH did not receive
      antihypertensives during their pregnancy, whereas those with confirmed EH
      received oxprenolol or methyldopa. Women with WCH had repeated 24-hour ABPM
      and/or BP assessments in a pregnancy day assessment unit until delivery. MAIN
      OUTCOME MEASURE: The development of PE in women with WCH or EH. RESULTS: The
      overall prevalence of WCH was 32%. Half retained this phenomenon throughout
      pregnancy and had good pregnancy outcomes. Forty percent developed (benign)
      gestational hypertension and also had good pregnancy outcomes while 8% developed
      proteinuric PE, significantly fewer than in women with confirmed EH (22%), P=
      0.008. No BP parameter at study entry permitted discrimination between those
      women with WCH who retained this phenomenon and those who developed GH or PE.
      CONCLUSION: WCH is a common phenomenon in pregnant women who appear to have EH
      according to routine BP measurement early in pregnancy. Antihypertensives may be
      withheld from this group initially and they can be advised they will have better
      pregnancy outcomes than women with true EH. However, continued monitoring
      throughout pregnancy remains important to detect the small group of white coat
      hypertensives who develop PE.

PMID- 15842285
TI  - Are league tables controlling epidemic of caesarean sections in South Korea?
AB  - OBJECTIVE: To assess the impact of the publication of hospital caesarean section
      rates on the reduction of these rates in South Korea, and explore associated
      factors contributing to the decrease. DESIGN: Observational study. SETTING: South
      Korea. SAMPLE: Two hundred and sixty-three hospitals in South Korea. METHODS: The
      caesarean section rates of 263 hospitals, before and after the release of
      caesarean section rates to the public, were obtained. The factors influencing the
      reduction in hospital caesarean section rates were also explored using multiple
      logistic regression. MAIN OUTCOME MEASURE: Hospital caesarean section rates.
      RESULTS: After the release of information in 2000, the total (clinic and
      hospital) caesarean section rates in 2000 and 2001 decreased to 38.6% and 39.6%,
      respectively, from 43.0% in 1999. Caesarean section rates for hospitals were
      45.9%, 42.7% and 44.6% in 1999, 2000 and 2001, respectively. Hospitals with the
      highest baseline caesarean section rates (OR 9.4, 95% CI 4.2-21.0) and highest
      number of deliveries (OR 8.1, 95% CI 2.1-31.1) were significant factors
      contributing independently to a decrease in caesarean section rates. Market
      share, competition, characteristics of revenue generation and ownership did not
      significantly influence the change of rates. CONCLUSION: The public release of
      information on caesarean section rates in Korea has reversed the ever-increasing
      trend in these rates. Hospitals with pre-existing high caesarean section rates or
      a larger number of deliveries were influenced by the information release and
      could be the main targets for interventions to decrease these rates.

PMID- 15842286
TI  - Prostaglandin E vaginal gel to treat dystocia in spontaneous labour: a
      multicentre randomised placebo-controlled trial.
AB  - OBJECTIVE: To test the safety and efficacy of prostaglandin E(2) (PgE(2)) as a
      treatment for dystocia in spontaneous labour. DESIGN: Randomised, double-blind,
      placebo-controlled trial. SETTING: Multicentre study in nine university
      affiliated hospitals in Canada. Population Three hundred and thiry-two
      nulliparous women with spontaneous labour at term. METHODS: Women who had
      progressed < 2 cm of cervical dilation in the 4 hours following the diagnosis of
      labour were randomly assigned to receive a single dose of either 1 mg (n= 112) or
      2 mg (n= 111) PgE(2) vaginal gel or placebo gel (n= 109). MAIN OUTCOME MEASURES:
      The primary outcome was resolution of dystocia, defined as a change in cervical
      dilatation of >0.5 cm per hour in the 6 hours following gel administration.
      Secondary outcomes were progress of labour, uterine hyperstimulation (more than
      five contractions in 10 minutes or a contraction lasting more than 2 minutes),
      use of oxytocin, method of delivery, maternal and neonatal morbidity. RESULTS:
      Dystocia resolved more often after PgE(2) 1 mg (49%), RR 1.53 (95% CI 1.1, 2.1)
      and PgE(2) 2 mg (49%), RR 1.5 (CI 1.1, 2.1), compared with placebo (32%).
      Hyperstimulation was increased after PgE(2) 2 mg treatment (15%), RR 5.6 (95% CI
      1.7, 18), but not after PgE(2) 1 mg (5.4%), RR 1.9 (CI 0.50, 7.6) when compared
      with placebo (2.8%). There was an increase in caesarean sections performed in the
      second stage of labour in the PgE(2) groups versus placebo. There were no
      differences in measures of maternal or neonatal morbidity. CONCLUSION: A single 1
      mg dose of PgE(2) vaginal gel is more effective than placebo in resolving
      dystocia, without increasing uterine hyperstimulation, but may be associated with
      an increase in the incidence of second stage caesarean section.

PMID- 15842287
TI  - Review of singleton fetal and neonatal deaths associated with cranial trauma and
      cephalic delivery during a national intrapartum-related confidential enquiry.
AB  - OBJECTIVE: To review delivery details of intrapartum-related fetal and neonatal
      deaths with singleton cephalic presentation and birthweight of 2500 g or more in
      which traumatic cranial or cervical spine injury or substantial difficulty at
      delivery of the head was a dominant feature. DESIGN: Review of freestyle summary
      reports and standard questionnaire responses submitted to the national
      secretariat for the Confidential Enquiry into Stillbirths and Death in Infancy
      (CESDI) during the 1994/1995 intrapartum-related mortality enquiry following
      regional multidisciplinary panel review. SETTING: United Kingdom. SAMPLE: Of the
      873 cases of intrapartum-related deaths reported in the 1994-1995 national
      enquiry, 709 weighed more than 2499 g. REPORTS: from 181 (89 from 1994 and 92
      from 1995) with a chance of meeting criteria for cranial or cervical trauma as
      significant contributors to death were examined in detail. Thirty-seven were
      judged to meet the criteria stated in the objectives (23 from 1994 and 14 from
      1995) and form the basis for this review. METHODS: Electronic and hand search of
      CESDI records relating to intrapartum-related deaths. MAIN OUTCOME MEASURES:
      Intrapartum events and features of care. RESULTS: There was evidence of fetal
      compromise present before birth in 33 of the 37 (89%) study group cases reviewed.
      One delivery was performed vaginally without instrumentation, and in one there
      was no attempt at vaginal delivery before caesarean section (CS) in the second
      stage of labour. Twenty-four cases (65%) were delivered vaginally and 11 (30%) by
      CS after failure to deliver vaginally with instruments. A single instrument was
      used in six cases of vaginal delivery (four ventouse and two Kjelland's forceps).
      At least two separate attempts with different instruments were made in 24 cases.
      Overall, the ventouse was used in 27 cases and forceps in 29 cases. In six cases,
      three separate attempts were made with at least two different instruments, all of
      which included use of ventouse. The grade of operator was recorded in 27 cases.
      Of these, a consultant obstetrician was present at only one delivery and no
      consultant was recorded to have made the first attempt to deliver a baby. In six
      cases, shoulder dystocia was also reported. CONCLUSIONS: This study suggests a
      lower incidence of death from difficult cephalic delivery and cranial trauma than
      previously reported. The CESDI studies were believed to have achieved high levels
      of ascertainment for all intrapartum-related deaths from which the cases reported
      here were selected. Strictly applied entry criteria used in this study could have
      restricted the number of cases considered as could limited in vivo or postmortem
      investigations and lack of detailed autopsy. When cranial traumatic injury was
      observed, it was almost always associated with physical difficulty at delivery
      and the use of instruments. The use of ventouse as the primary or only instrument
      did not prevent this outcome. Some injuries occurred apparently without evidence
      of unreasonable force, but poorly judged persistence with attempts at vaginal
      delivery in the presence of failure to progress or signs of fetal compromise were
      the main contributory factor regardless of which instruments were used.

PMID- 15842288
TI  - Tocolysis for repeat external cephalic version in breech presentation at term: a
      randomised, double-blinded, placebo-controlled trial.
AB  - BACKGROUND: External cephalic version (ECV) reduces the incidence of breech
      presentation at term and caesarean section for non-cephalic births. Tocolytics
      may improve success rates, but are time consuming, may cause side effects and
      have not been proven to alter caesarean section rates. The aim of this trial was
      to determine whether tocolysis should be used if ECV is being re-attempted after
      a failed attempt. OBJECTIVE: To determine whether tocolysis should be used if ECV
      is being re-attempted after a failed attempt. DESIGN: Randomised, double-blinded,
      placebo-controlled trial. SETTING: UK teaching hospital. POPULATION: One hundred
      and twenty-four women with a breech presentation at term who had undergone an
      unsuccessful attempt at ECV. METHODS: Relative risks with 95% confidence
      intervals for categorical variables and a t test for continuous variables.
      Analysis was by intention to treat. MAIN OUTCOME MEASURES: Incidence of cephalic
      presentation at delivery. Secondary outcomes were caesarean section and measures
      of neonatal and maternal morbidity. RESULTS: The use of tocolysis for a repeat
      attempt at ECV significantly increases the incidence of cephalic presentation at
      delivery (RR 3.21; 95% CI 1.23-8.39) and reduces the incidence of caesarean
      section (RR 0.33; 95% CI 0.14-0.80). The effects were most marked in multiparous
      women (RR for cephalic presentation at delivery 9.38; 95% CI 1.64-53.62).
      Maternal and neonatal morbidity remain unchanged. CONCLUSIONS: The use of
      tocolysis increases the success rate of repeat ECV and reduces the incidence of
      caesarean section. A policy of only using tocolysis where an initial attempt has
      failed leads to a relatively high success rate with minimum usage of tocolysis.

PMID- 15842289
TI  - Obstetric outcome in women with subfertility.
AB  - BACKGROUND: It has been suggested that a history of subfertility is associated
      with increased obstetric and perinatal risks. It is unclear if the cause is
      inherent characteristics in the women or the fertility treatment. OBJECTIVES: To
      compare the obstetric and perinatal risks of singleton pregnancies in women with
      a history of subfertility in comparison with the general population. DESIGN:
      Population cohort. SETTING: Aberdeen, Scotland. POPULATION: Cases were women
      attending the Fertility Clinic between 1989 and 1999 who subsequently went on to
      have singleton pregnancies. Controls included the general population of women who
      delivered singletons over the same period. METHODS: We performed a retrospective
      cohort study to investigate the obstetric outcome of singleton pregnancies in
      women with subfertility. The general population of women who delivered singletons
      over the same period served as controls. MAIN OUTCOME MEASURES: Obstetric and
      perinatal complications in singleton pregnancies. RESULTS: Maternity records were
      available for a total of 1437 subfertile women and 21,688 controls. Subfertile
      women were older [mean (SD) age: 31 (4.7) years vs 27 (5.4) years, P < 0.01] and
      more likely to be primiparous (70% vs 65%, P < 0.001). After adjusting for age
      and parity, subfertile women were at increased risk of pre-eclampsia (OR 1.9, 95%
      CI 1.5-2.5), placenta praevia (OR 3.9, 95% CI 2.2-7.0) and placental abruption
      (OR 1.8, 95% CI 1.1-3.0), and more likely to undergo induction of labour (OR 1.5,
      95% CI 1.3-1.6), caesarean section (OR 2.1, 95% CI 1.8-2.4) and instrumental
      delivery (OR 2.2, 95% CI 1.8-2.6), and deliver low birthweight (OR 1.4, 95% CI
      1.3-1.7) and preterm (OR 1.7, 95% CI 1.2-2.2) infants. There were no differences
      between treatment-related and treatment-independent pregnancies. CONCLUSION:
      Subfertile women are at higher risk of obstetric complications, which persist
      after adjusting for age and parity.

PMID- 15842290
TI  - Rapid reduction of leiomyoma volume during treatment with the GnRH antagonist
      ganirelix.
AB  - OBJECTIVE: To assess maximal volume reduction of leiomyomas and uterus and the
      duration of treatment required to reach these reductions with daily GnRH
      antagonist treatment. DESIGN: Prospective, open-label study. SETTING: Large
      teaching hospital in The Netherlands. POPULATION: Premenopausal women with
      symptomatic fibroids, who were scheduled for surgery. METHODS: Twenty women were
      treated with daily 2 mg of subcutaneous ganirelix. Prior to the first injection
      and weekly during treatment, the volume of leiomyomas and the uterus were
      assessed by ultrasound (USS) and serum hormones were measured. Prior to treatment
      and when maximal size reduction was observed by USS, the volume of the leiomyomas
      and the uterus were also assessed by magnetic resonance imaging (MRI). MAIN
      OUTCOME MEASURES: Leiomyoma and uterine size reduction, time to maximal
      reduction. RESULTS: One woman was excluded from the study due to incorrect
      administration dose of ganirelix. Data on the remaining 19 women (average age 39
      years) with subserosal (n= 9), submucosal (n= 7), intramural (n= 10) and
      transmural (n= 1) leiomyomas were evaluated. Baseline leiomyoma volumes ranged
      from small (3-4 mL) to large (>1000 mL). The median duration of treatment up to
      maximal leiomyoma size reduction was 19 days (range 1-65 days). The maximal size
      reduction in leiomyomas measured by USS was -42.7% (-77.0% to 14.1%) and -29.2% (
      62.2% to 35.6%) by MRI. Comparable uterine size reductions of -46.6% (-78.6% to 
      6.1%) and -25.2% (-63.6% to 28.9%) were observed by USS and MRI. During the first
      three weeks of treatment, 8 out of 19 women reported adverse events related to
      the induced hypoestrogenic state. Most of these events resolved within one week
      after treatment was discontinued. CONCLUSION: Daily treatment with 2 mg of
      ganirelix results in rapid reduction of leiomyoma and uterine volume in
      premenopausal women with minor side effects. If longer-acting GnRH antagonists
      become available, pretreatment with GnRH antagonist should be preferred over GnRH
      agonists prior to surgery.

PMID- 15842291
TI  - Female genital appearance: "normality" unfolds.
AB  - OBJECTIVE: To describe variations in genital dimensions of normal women. DESIGN:
      Observational cross-sectional study. SETTING: Elizabeth Garrett Anderson
      Hospital, University College Hospital NHS Trust, London, UK. POPULATION: Fifty
      premenopausal women having gynaecological procedures not involving the external
      genitalia under general anaesthetic. METHODS: A cross sectional study using
      digital photography and measurements of the external genitalia. MAIN OUTCOME
      MEASURES: Clitoral size, labial length and width, colour and rugosity, vaginal
      length, distance from clitoris to urethral orifice, distance from posterior
      fourchette to anterior anal margin. RESULTS: A wide range of values were noted
      for each measurement. There was no statistically significant association with
      age, parity, ethnicity, hormonal use or history of sexual activity. CONCLUSION:
      Women vary widely in genital dimensions. This information should be made
      available to women when considering surgical procedures on the genitals,
      decisions for which must be carefully considered between surgeon and woman.

PMID- 15842292
TI  - The association of ambient outdoor temperature throughout pregnancy and offspring
      birthweight: findings from the Aberdeen Children of the 1950s cohort.
AB  - BACKGROUND: We assessed the effect of mean ambient outdoor temperature during
      gestation on birthweight. OBJECTIVE: To assess the effect of mean ambient outdoor
      temperature during gestation on birth weight. DESIGN: Birth cohort study with
      record linkage to climate databases. SETTING: Aberdeen, Scotland. SAMPLE: A total
      of 12,150 individuals born in Aberdeen, Scotland between 1950 and 1956.
      METHODOLOGY/PRINCIPAL FINDINGS: Perinatal data from a cohort of 12,150
      individuals born in Aberdeen, Scotland between 1950 and 1956 were linked to daily
      outdoor temperature data. Birthweight was seasonally patterned, with lowest
      birthweights among those born in the winter months (December-February) and
      highest birthweights among those born in the autumn months (September-November);
      P= 0.01 for joint sine-cosine functions. Mean ambient outdoor temperature during
      the first trimester of pregnancy was inversely associated with birthweight and
      mean ambient outdoor temperature during the third trimester of pregnancy was
      positively associated with birthweight. In fully adjusted (for sex, maternal age,
      birth year, birth order and social class) models a 1 degrees C increase in mean
      ambient outdoor temperature in the mid 10-day period of the first trimester was
      associated with a 5.4-g (95% confidence interval [CI] 2.9, 7.9 g) decrease in
      birthweight, whereas a 1 degrees C increase in the mid 10-day period of the third
      trimester was associated with a 1.3-g (95% CI 0.50, 2.1 g) increase in
      birthweight. Ambient outdoor temperature in the first trimester of pregnancy
      explained the seasonal patterning of birthweight. MAIN OUTCOME MEASURE:
      Birthweight. RESULTS: Birthweight was seasonally patterned, with lowest
      birthweights among those born in the winter months (December-February) and
      highest birthweights among those born in the autumn months (September-November);
      P= 0.01 for joint sine-cosine functions. Mean ambient outdoor temperature during
      the first trimester of pregnancy was inversely associated with birthweight and
      mean ambient outdoor temperature during the third trimester of pregnancy was
      positively associated with birthweight. In fully adjusted (for sex, maternal age,
      birth year, birth order and social class) models a 1 degrees C increase in mean
      ambient outdoor temperature in the mid 10-day period of the first trimester was
      associated with a 5.4 g (95% confidence interval 2.9, 7.9 g) decrease in
      birthweight, whereas a 1 degrees C increase in the mid 10-day period of the third
      trimester was associated with a 1.3 g (95% confidence interval 0.50, 2.1 g)
      increase in birthweight. Ambient outdoor temperature in the first trimester of
      pregnancy explained the seasonal patterning of birthweight. CONCLUSION: Higher
      ambient outdoor temperature in the first trimester of pregnancy and/or lower
      ambient outdoor temperature in the third trimester are associated with reduced
      offspring birthweight. With the increasing occurrence of temperature extremes, in
      particular, heat waves, these findings, if replicated in other studies, have
      important public health implications.

PMID- 15842294
TI  - Agreement studies in obstetrics and gynaecology: inappropriateness, controversies
      and consequences.
AB  - A literature review was performed to assess how agreement has been measured in
      obstetrics and gynaecology. Inappropriate or controversial measures were often
      used. The possible consequences of these inadequacies on validity studies and
      randomised controlled trials are shown in case examples. The association of two
      measures, proportions of agreement and kappa for categorical variables, and
      limits of agreement and intraclass correlation coefficient for continuous
      variables, is encouraged in agreement studies, until new and better ways of
      assessing agreement are found.

PMID- 15842293
TI  - How much variation in CS rates can be explained by case mix differences?
AB  - OBJECTIVE: To quantify the amount of variation in caesarean section (CS) rates
      between maternity units explained by case mix differences. DESIGN: Cross
      sectional study. SETTING: All 216 maternity units in England and Wales.
      POPULATION: Women giving birth at these maternity units between May and July
      2000. METHODS: Logistic regression models were developed to investigate the
      relationship between case mix characteristics, and odds of (i) CS before labour,
      (ii) CS in labour. Using these results, overall CS rates standardised for case
      mix were calculated for each maternity unit. Random-effects meta-analysis was
      used to examine heterogeneity between maternity units. MAIN OUTCOME MEASURES: CS
      before labour and CS during labour. RESULTS: Adjustment for case mix differences
      between maternity units explained 34% of the variance in CS rates. Odds of CS
      (before and in labour) increased with maternal age. Women from ethnic minority
      groups had lower odds of CS before labour, and increased odds of CS in labour.
      Women with a previous vaginal delivery had lower odds of CS, although the
      magnitude of this for CS before and in labour is markedly different. CONCLUSIONS:
      Case mix adjustment is important to enable understanding of the factors that
      influence the CS rate. These include organisational and staffing levels as well
      as women's preferences for childbirth and clinician's attitudes. An understanding
      of how these factors influence the CS rate is essential for evaluation of quality
      and appropriateness of obstetric care provided to women.

PMID- 15842295
TI  - Cystoscopy to investigate suprapubic catheter blockage: plugging of the side
      holes by bladder mucosa.

PMID- 15842296
TI  - Multicentric reticulohistiocytosis and pregnancy.

PMID- 15842297
TI  - Cephalic replacement for shoulder dystocia: three cases.

PMID- 15842298
TI  - The use of the "tamponade test" to stop massive obstetric haemorrhage in placenta
      accreta.

PMID- 15842299
TI  - Acquired haemophilia and postpartum haemorrhage treated with internal pudendal
      embolisation.

PMID- 15842300
TI  - Early extrusion of bilateral Filshie clips after laparoscopic sterilisation.

PMID- 15842301
TI  - US versus MRI in prenatal diagnosis: where are we going?

PMID- 15842302
TI  - Pharmacovigilance of veterinary medicines.

PMID- 15842304
TI  - Veterinary pharmacovigilance. Part 1. The legal basis in the European Union.
AB  - Pharmacovigilance is a growing discipline and nowhere is this more true than in
      the context of the legislative requirements for veterinary pharmacovigilance
      within the European Union (EU), or more specifically, within the European
      Economic Area. Since 1995, the legislation governing the authorization of
      veterinary medicinal products in the EU has resulted in the older national
      procedures being replaced by the mutual recognition procedure and the centralized
      procedure. Also since 1995, the regulatory requirements for pharmacovigilance
      have developed and grown, as have the associated guidelines. The recent review of
      European veterinary medicines legislation, which concluded with the publication
      of an amending directive and a new regulation in March 2004, has introduced
      refinements to the pharmacovigilance system. This paper examines the EU
      legislation governing the authorization of veterinary medicinal products,
      including the elaboration of maximum residue limits, and the way in which this
      relates to the requirements of pharmacovigilance.

PMID- 15842305
TI  - Veterinary pharmacovigilance. Part 2. Veterinary pharmacovigilance in practice --
      the operation of a spontaneous reporting scheme in a European Union country --
      the UK, and schemes in other countries.
AB  - Veterinary pharmacovigilance, as it operates in the European Union (EU), covers a
      very broad remit, including adverse effects in treated animals, exposed humans
      and the environment, and in addition, it extends to cover the violation of
      maximum residue limits. The mainstay of veterinary pharmacovigilance is the
      spontaneous reporting scheme working along side other systems such as those
      reporting on residues surveillance. One of the most well established schemes in
      the EU is that operating in the UK and this paper examines the evolution of that
      scheme and some of its findings, data from other countries, and information
      available from the literature. It also tentatively examines the ways that
      pharmacovigilance can be used for regulatory purposes, and the contribution from
      pharmacoepidemiology.

PMID- 15842306
TI  - Veterinary pharmacovigilance. Part 3. Adverse effects of veterinary medicinal
      products in animals and on the environment.
AB  - Like humans, animals may experience adverse effects when treated with medicinal
      products. These effects may be related to the pharmacological or toxicological
      properties of the substances used or they may arise because of hypersensitivity.
      Veterinary medicinal products may also possess the ability to harm the
      environment. This paper reviews the potential of veterinary medicinal products to
      cause adverse effects in animals and on the environment.

PMID- 15842307
TI  - Veterinary pharmacovigilance. Part 4. Adverse reactions in humans to veterinary
      medicinal products.
AB  - Although seemingly rare, adverse reactions to veterinary products do occur. These
      may arise from inadvertent exposure during use or as a result of occupational
      accidents. They are often mild in nature and include adverse effects such as
      minor skin reactions. However, more serious reactions may occur, and they are not
      restricted to the effects of the veterinary medicines themselves. For example,
      high-pressure injection injuries may occur as a result of accidents occurring
      during animal vaccination operations. This paper reviews some of these events,
      mentions where appropriate the regulatory actions taken, and describes some of
      the measures used to minimise such effects in the future, and serves to bring the
      issues discussed here to the attention of pharmacologists,
      pharmacoepidemiologists and others who train those who use veterinary medicinal
      products.

PMID- 15842308
TI  - Veterinary pharmacovigilance. Part 5. Causality and expectedness.
AB  - In the European Union and elsewhere there is a requirement to ascribe causality
      to adverse drug reactions which occur in treated animals. In the EU, the ABON
      system of causality assessment is used but the assignment of causality assigned
      is not always self evident, and it may be complicated for a variety of reasons.
      In this paper, the approaches to causality assessment, based on a number of key
      criteria which examine the administration of the drug in relation to the sequence
      of ensuing events and the presence of biological plausibility are examined, along
      with the utility of using algorithms to facilitate this process. Unexpected
      adverse drug reactions usually require expedited reporting, depending on national
      or regional regulatory requirements. Again, deciding on what might constitute an
      expected (or unexpected) adverse reaction, particularly when a product may be
      intended for use in a number of species, and when within any one species a number
      of breeds may be treated, is not necessarily a straightforward issue. However, an
      approach to facilitate the decision- making process, based on a similar approach
      used in the pharmacovigilance of human medicinal products is discussed.

PMID- 15842309
TI  - Veterinary pharmacovigilance. Part 6. Predictability of adverse reactions in
      animals from laboratory toxicology studies.
AB  - Toxicological studies are conducted on constituents of veterinary medicinal
      products for a number of reasons. Aside from being a requirement of legislation,
      they are carried out for predictive purposes in the assessment of user safety or
      for the determination of consumer safety, for example, in the elaboration of
      maximum residue limits or tolerances. Alternatively, the results of toxicology
      studies may be available as they have been generated for registration of the drug
      for human medicinal purposes. This paper examines if the results of such studies
      have any predictive value for adverse reactions, which might occur during
      clinical use in animals. A number of adverse reactions, notably the Type A
      (toxicology or pharmacology dependent) should be predictable from these
      laboratory studies. However, as with human pharmaceutical products, they have
      less utility in predicting Type-B reactions (idiosyncratic in nature).

PMID- 15842312
TI  - Ethical dilemma and moral distress: proposed new NANDA diagnoses.
AB  - PURPOSE: To propose two NANDA diagnoses--ethical dilemma and moral distress--and
      to distinguish between the NANDA diagnosis decisional conflict and the proposed
      nursing diagnosis of ethical dilemma. SOURCES USED: Journal articles, books, and
      focus group research findings. DATA SYNTHESIS: Moral/ethical situations exist in
      health care. Nurses' experiences of ethical dilemmas and moral distress are
      extrapolated to the types and categories of ethical dilemmas and moral distress
      that patients experience and are used as the basis for development of two new
      nursing diagnoses. CONCLUSION: The two proposed NANDA diagnoses fill a void in
      current standardized terminology. PRACTICE IMPLICATIONS: It is important that
      nurses have the ability to diagnose ethical or moral situations in health care.
      Currently, NANDA does not offer a means to document this important phenomenon.
      The creation of two sets of nursing diagnoses, ethical dilemma and moral
      distress, will enable nurses to recognize and track nursing care related to
      ethical or moral situations.

PMID- 15842313
TI  - Nursing-sensitive outcome reliability testing in a tertiary care setting.
AB  - PURPOSE: To describe nursing outcomes classification (NOC) that are most relevant
      for, specialty acute care nursing practice, and to assess the adequacy of
      measures. METHODS: Data were collected on 434 patients during the 14-month data
      collection period at a tertiary care center: cardiac surgery intensive care (n =
      76), cardiac transplant unit (n = 153), and medical unit (n = 205). FINDINGS:
      Thirty-six NOC outcomes were used 10 or more times during the study. Of those, 16
      had an inter-rater reliability of 75% or higher. CONCLUSIONS: NOC outcomes show
      promise for accurately documenting the effectiveness of nursing interventions.
      Further study is needed to develop meaningful analysis of the documented NOC
      outcomes and efficiently integrate NOC into electronic documentation systems.
      PRACTICE IMPLICATIONS: Increased familiarity with NOC allowed nursing staff to
      determine which outcomes comprise core nursing-sensitive outcomes for their
      clinical setting.

PMID- 15842314
TI  - Regulation and profession-building: a personal perspective.

PMID- 15842316
TI  - Unique partnership supports a malaria capacity building program in Zambia.

PMID- 15842320
TI  - Counterfeits kill--what are we doing about them?

PMID- 15842321
TI  - Lifestyle practices of Jordanian pregnant women.
AB  - BACKGROUND: Although many improvements have been made in the area of women's
      health in Jordan, women during pregnancy still face many health problems that put
      their lives at risk. This is evident in the relatively high Maternal Mortality
      Rate, anaemia, low birth weight and other problems related to their lifestyle
      practices during pregnancy (Jordanian Ministry of Health 1998). PURPOSE: To
      describe the health-promoting lifestyle behaviours of Jordanian pregnant women.
      The Maternal Health Promoting Lifestyle Profile (MHPLP), based on the Health
      Promotion Model, was modified to measure maternal practices. A representative
      sample of 400 Jordanian pregnant women in their 20th week of gestation or beyond
      were recruited from five public Maternal and Child Health Centres in the city of
      Irbid, in the northern part of Jordan. The MHPLP measures six dimensions:
      physical activity, stress management, self-actualization, nutrition, health
      responsibility and interpersonal support. Data were analysed by using descriptive
      analysis. RESULTS: The women reported high scores on health responsibility and
      self-actualization, moderate scores on interpersonal support and nutrition, and
      low scores on physical activity and stress management behaviours. CONCLUSIONS AND
      IMPLICATIONS FOR POLICY, PRACTICE AND RESEARCH: The findings have implications
      for the quality of care delivered through the maternal and child health services.
      Health promotion and healthy lifestyle need to be an integral part of health
      services provided for pregnant women. Further research is needed to develop an
      instrument that integrates the cultural beliefs relating to lifestyle practices
      of Jordanian pregnant women mainly in the areas of physical activities and stress
      management. Policy implications of the findings are discussed.

PMID- 15842322
TI  - Men's experiences of vasectomy in the Brazilian Public Health Service.
AB  - BACKGROUND: Vasectomy was legalized in Brazil in 1996 and is freely available in
      some public health institutions. Nevertheless, the prevalence of vasectomy is
      less than 4.4%, demonstrating how rarely this contraceptive resource is used. The
      promotion of greater male involvement in reproductive health was one of the
      recommendations of the Cairo International Conference of Population and
      Development (ICPD). RESEARCH OBJECTIVE: To describe the experiences of a group of
      men who had had vasectomy. METHOD: The thematic oral history method was used.
      Twenty men vasectomized in a Sao Paolo State Health Service Clinic were
      interviewed. Each tape-recorded narrative was analysed through transcription,
      textualization, and transcreation, a process used to transform the oral history
      into written narrative form. From each narrative a 'vital tone' was extracted,
      revealing the essence of the individual experience. All the data were analysed
      under an inductive and interpretative process. The similarities among histories
      were identified, and submitted to a process of reduction in order to develop
      descriptive categories. RESULTS: The following descriptive categories were
      developed from the men's experiences: Misconceptions regarding vasectomy that
      were overcome after hearing positive results expressed by other men; Vasectomy
      was the last solution for a couple's troubles related to contraceptive methods;
      Satisfaction related to professional support received during the process of
      searching for a method and deciding upon vasectomy; Satisfaction was the main
      feeling expressed following vasectomy and they recommended this contraceptive
      method to other men; Men's behaviours towards postvasectomy control was divergent
      despite the professional guidance. CONCLUSIONS: An integrated public policy is
      required to promote male involvement in reproductive health. Family planning
      programmes must be meaningful socioculturally and the inclusion of men in these
      programmes is recommended. The use of anonymized videotaped narratives or the
      recruitment of the men themselves during counselling about this method would be
      helpful for the resolution of reservations related to vasectomy. All the
      interviewed men expressed satisfaction with vasectomy and this feeling was mainly
      based on the certainty of the preservation of sexual performance. LIMITATIONS: A
      third of those invited for interview did not attend.

PMID- 15842323
TI  - Jordanian married Muslim women's intentions to use oral contraceptives.
AB  - BACKGROUND: High fertility rates and moderate to low contraceptive use in the
      Arab Islamic countries, and Jordan in particular, are issues of international
      nursing importance. AIM: By using the Theory of Planned Behaviour (TPB) as the
      conceptual framework, the relationships between married Jordanian Muslim women's
      previous contraceptive use, type of experience, and intention to use oral
      contraceptives (OCs) were examined. The relationship between selected demographic
      variables and intention to use OCs was also examined. METHODS: The study was part
      of a large cross-sectional survey. The Intention to Use Oral Contraceptive Tool
      was used to elicit participants' intentions and beliefs regarding oral
      contraceptive use. SAMPLE: The study sample was composed of 245 Jordanian married
      Muslim women. RESULTS: Results revealed a significant relationship between
      previous oral contraceptive use and intention to use OCs. The relationships
      between type of experience, whether successful or unsuccessful, with previous OC
      use, and intention to use OCs were not significant. CONCLUSION: Nursing
      implications regarding the provision of family planning services that are
      sensitive to Jordanian Muslim women's religious preferences are discussed.

PMID- 15842324
TI  - Risk and protective behaviours of bisexual minority women: a qualitative
      analysis.
AB  - BACKGROUND: Public health messages urging women to seek health care services such
      as sexually transmitted diseases (STD) and cervical cancer screening or family
      planning services fail to address women who have sex with women (WSW). This
      negligence may have led to a false sense of security amongst WSW concerning
      sexual risk behaviour. Research has shown that WSW engaged in more high-risk
      sexual behaviours than heterosexual women. WSW has been identified as an
      important vector in the spread of STDs in all populations because of bisexuality.
      To prevent and reduce transmission of STDs amongst WSW, perceptions of risk for
      STD amongst WSW need to be understood so that effective interventions may be
      developed. AIM: To describe the relationship between sexual risk and protective
      behaviour and STD transmission amongst bisexual minority women with a history of
      STD. METHODS: Life history methods were used to interview 23 African-American
      bisexual women with a history of STD. FINDINGS: Various themes unfolded during
      analysis of the patient interviews, including bisexual women's perceptions of STD
      risk, the context of sexual relationships with women and STD prevention,
      screening, and treatment practices. CONCLUSIONS: The contexts of sexual
      relationships including multiple or concurrent partner relationships with both
      men and women placed these women at high risk for STD. Regardless of the type of
      relationship or belief it is possible to get an STD, protection was often not
      used. These circumstances identify an extremely high-risk population of women
      with need for more extensive research to identify strategies for health care
      interventions.

PMID- 15842325
TI  - Nursing, midwifery and allied health education programmes in Afghanistan.
AB  - BACKGROUND: In 2001, Afghanistan was the centre of the world's attention. By
      2002, following 23 years of internal conflict - including Soviet invasion, civil
      war and Taliban rule, plus 3 years of drought, the country was just beginning the
      process of re-establishing its internal structures and processes. In the health
      sector, this included the revival of the Ministry of Health (MOH). The MOH was
      assisted in its efforts by multiple partners, including the UN, donor and aid
      agencies, and a variety of non-governmental organizations. The author served as a
      consultant to the Aga Khan University School of Nursing, in partnership with the
      World Health Organization and the MOH, as it took on the work of strengthening
      nursing, midwifery and allied health education programmes for Afghanistan. AIM:
      This paper will focus on the initial assessment of that sector. It will describe
      the situation as it existed in 2002, by examining the Kabul Institute of Health
      Sciences (IHS) and then turn briefly to the current state of affairs.
      CONCLUSIONS: Despite the uncertainties of daily life in Afghanistan, the country
      has successfully initiated the reconstruction process. In the health sector, this
      can be seen in the work done at the Kabul IHS. Progress has been made in a number
      of areas, most notably in development and implementation of nursing and midwifery
      curricula. However, no one would deny that much more work is needed.

PMID- 15842326
TI  - Iranian student nurses' experiences of clinical placement.
AB  - BACKGROUND: Nursing as a practice-based profession requires that student nurses
      learn how to become professional in the clinical environment. Many studies have
      addressed student nurses' clinical learning and related problems, but few have
      explored the whole clinical experience of being a student nurse. AIM: To
      understand and gain deeper insight into Iranian student nurses' lived experience
      of clinical placement. METHOD: Five student nurses were interviewed about their
      clinical experience during clinical placement. The researchers analysed the
      verbatim transcripts using van Manen's phenomenological methodology, keeping in
      mind the recommended six research activities. FINDINGS: Five themes emerged by
      which the phenomenon of clinical experience could be illustrated. These themes
      were: caring-orientated relationships, attractive aspects of clinical experience,
      finding oneself in the clinical milieu, being supportive to classmates, and
      actualizing potential. Fourteen subthemes expanded and clarified the meaning of
      these themes. CONCLUSION: The attention paid and acknowledgement given to
      'caring' and 'knowledge' by the student nurses showed that they are progressing
      toward their ultimate goal of being professional nurses. The student nurses'
      awareness of 'what is going on there?' and also support from other significant
      people facilitates the students' adaptation process and guarantees this progress.

PMID- 15842327
TI  - Place(ment) matters: students' clinical experiences and their preferences for
      first employers.
AB  - BACKGROUND: Although a significant volume of nursing research has focused on
      students' experiences of clinical placements, to date, none has considered these
      experiences in the context of workforce recruitment and specifically how they may
      impact upon preferences for working for health care providers. METHODS: In this
      context, the research used a place-sensitive geographical perspective and a
      combined questionnaire (n = 650), interview (n = 30) and focus group (n = 7)
      method to collect data on the complex range of clinical experiences which
      together impact upon the perceived attractiveness of different health care
      settings. FINDINGS: The data identified a range of experiential factors
      associated with mentorship, ward management, learning opportunities and racism.
      An important finding was that although students' experiences are obtained at the
      micro ward level, even if they may not necessarily reflect what happens
      throughout the hospital, they potentially impact, both positively and negatively,
      upon their broader perceptions of the hospital and the likelihood of seeking work
      there. IMPLICATIONS: The study highlighted a variety of issues that should be
      addressed by both higher education institutions and hospitals so that they may be
      able to provide a more consistent and positive experience for students. In the
      longer term, this may pay dividends through increased recruitment of new
      graduates.

PMID- 15842328
TI  - Violence towards nursing staff in emergency departments in one Turkish city.
AB  - AIM: To determine the incidence of violence faced by nurses in emergency
      departments (ED) in a Turkish city, whether any of the incidents were reported
      and what legal action was taken. The second aim was to identify nurses' attitudes
      towards these incidents and the relevance of their professional background.
      METHODS: Data were collected by questionnaire from the nurses working in the ED
      of four major hospitals in Izmir, Turkey. The questionnaire consisted of 34
      questions seeking socio-demographic data, information on verbal and physical
      victimization and legal processes. RESULTS: Sixty-six nurses (72%) agreed to
      participate in the study. One third (34.8%) of participants were relatively new
      in the profession (0-5 years), and the majority of nurses (71.2%) had an ED
      experience of less than 5 years. The incidence of verbal violence (98.5%) was
      significantly more frequent than physical violence (19.7%). However, most
      incidents remained unreported (83.5%); most of the reported cases did not result
      in legal action (63.7%). Almost half of the nurses believed that possible
      explanations for the violent incidents they faced were because they were less
      competent and inexperienced in the profession than more senior colleagues.
      DISCUSSION: Victimized respondents mostly preferred to remain silent and did not
      report the incidents to the hospital administration since they believed that this
      would not result in legal action. It seems evident that our country lacks legal
      processes concerning job (workplace) violence. Effective legislative arrangements
      are necessary. Nurses and other ED staff also need continuing education
      concerning their rights and personal safety.

PMID- 15842329
TI  - Temporal events in the intravenous challenge model for experimental Candida
      albicans infections in female mice.
AB  - We characterized the intravenous (i.v.) challenge model for disseminated Candida
      albicans infection in female BALB/c and DBA/2 mice. Clearance of fungi from the
      bloodstream and appearance of fungi in tissues were measured at intervals after
      challenge with various doses of C. albicans. The wild-type isolate SC5314 and
      derived strains CAF2-1 and CAI-4 transformed with CIp10 were of equal virulence
      in the model. Variability in mouse survival times, kidney fungal burdens and
      cachexia was lowest when challenge inocula were within the range 10(4)-10(5) CFU
      g(-1) body weight in BALB/c mice, but brain fungal burdens and outcomes in DBA/2
      mice were variable for all inocula tested. Critical times in the development of
      infections in optimally challenged BALB/c mice were at 5-10 h (bloodstream fully
      cleared of fungi), 24 h (start of exponential fungal growth in kidneys) and 48 h
      (50% of blood cultures become positive). Differential involvement of right and
      left kidneys occurred almost exclusively in mice challenged with <2 x 10(4) CFU
      g(-1). We conclude that the i.v. challenge model in female BALB/c mice is now
      sufficiently well characterized to permit more refined experimentation in future
      virulence studies with C. albicans mutants.

PMID- 15842330
TI  - Scutular tinea of the scrotum: report of two cases.
AB  - Infections caused by dermathophytes in the scrotal skin are uncommon especially
      due to Microsporum gypseum, which may form scutular or favus-like lesions. We
      report two patients with this type of tinea: one immune suppressed by HIV
      infection and another immunocompetent without comorbidity. In the literature we
      found only two reports in immunocompetent patients and some in immune suppressed
      with similar symptoms.

PMID- 15842331
TI  - Itraconazole in the treatment of acute and recurrent vulvovaginal candidosis:
      comparison of a 1-day and a 3-day regimen.
AB  - Itraconazole is a systemic triazole with a broad-spectrum antifungal effect which
      belongs to a standard choice for the treatment of vulvovaginal candidosis. Thirty
      four patients with acute and 26 patients with recurrent form of culture
      documented attacks of vulvovaginal candidosis were evaluated. There was frequent
      discrepancy between severe symptoms and weaker signs in patients with recurrent
      form than in the group with acute sporadic form. Eighteen patients with the acute
      form and 13 patients with the recurrent form of vulvovaginal candidosis received
      1-day therapy (twice 200 mg of itraconazole in 1 day). Sixteen patients with the
      acute form and 13 patients with the recurrent form received 3-day therapy (200 mg
      of itraconazole daily for three following days). The cure rates 1 month after
      treatment were 97.1 and 76.9% in patients with the acute sporadic and recurrent
      form of vulvovaginal candidosis, respectively. Positive cultures in the latter
      group documented relapses. These clinical failures were not related to the
      resistance of yeasts to itraconazole. With the exception of one case of alopecia
      areata, side effects were minimal. The application of the long-term regimens and
      suppressive therapy with azole drugs is suggested in patients with recurrent
      vulvovaginal candidosis.

PMID- 15842332
TI  - Antifungal activity of Ocimum gratissimum towards dermatophytes.
AB  - The development of more effective and less toxic antifungal agents is required
      for the treatment of dermatophytosis. Plants and their preparations have been
      used as medicines against infectious diseases. Extracts of Ocimum gratissimum
      leaves were investigated for in vitro antifungal activity, using agar dilution
      technique against dermatophytes. The extracts (hexane, chloroform fractions, the
      essential oil and eugenol) produced antifungal activities against Microsporum
      canis, M. gypseum, Trichophyton rubrum and T. mentagrophytes. Trichophyton
      rubrum, the most common aetiological agent of dermatophytosis in Goiania, state
      of Goias, Brazil, was also the most susceptible dermatophyte. The hexane fraction
      and eugenol were the most active. Hexane fraction inhibited the growth of 100% of
      dermatophytes at a concentration of 125 microg ml(-1), while eugenol inhibited
      the growth of 80% of dermatophytes at this same concentration. These results show
      that extracts of O. gratissimum are active in vitro against human pathogenic
      dermatophytes.

PMID- 15842333
TI  - Candidosis and aspergillosis as autopsy findings from 1994 to 2003.
AB  - We analysed the autopsy records of the Greifswald University Institute of
      Pathology (located in Eastern Germany) in respect of findings of candidosis and
      aspergillosis from 1994 to 2003. We also present eight immature aborted fetuses
      and premature infants with a mycosis. In a total of 2027 autopsies we found 164
      cases of invasive candidosis and aspergillosis (8.1%) including a combination of
      both on four occasions. Other authors cited between 0.7 and 7.3%. In these 10
      years in our material mycoses and in particular candidosis increased in spite of
      slightly decreased numbers of autopsies. The differences comparing the 5-years
      periods (1994-98 and 1999-2003) are highly significant for both mycoses and
      candidosis. They are not significant for aspergillosis. A similar relationship
      was observed in the distribution of mycotic organs and causative origin for
      candidosis alone. In the last 5 years the gastrointestinal and respiratory
      tracts, including the peritoneum, were more frequently infected by Candida. Non
      haematological neoplasia and pneumonia as basic diseases more often appeared in
      cases of candidosis. All eight immature aborted fetuses and premature infants
      suffered from candidosis. The survey confirms the importance of autopsy as a tool
      for education and quality control in medical diagnostic and therapeutic activity
      in the field of mycoses, too.

PMID- 15842334
TI  - Dermatophyte infections in the Ljubljana region, Slovenia, 1995-2002.
AB  - We studied dermatophyte infections in patients, examined in the Mycological
      Laboratory of the Department of Dermatology, University Medical Centre Ljubljana
      during the period 1995-2002. A total of 42,494 samples were collected from 33,974
      patients suspected to have dermatomycosis. Dermatophytes were identified in 8286
      (71.2%) positive cultures. Microsporum canis was the most frequent dermatophyte
      isolated (46.8%), followed by Trichophyton rubrum (36.7%), T. mentagrophytes var.
      interdigitale (7.9%) and T. mentagrophytes var. mentagrophytes (4.9%). Less
      frequently isolated were M. gypseum, T. verrucosum, Epidermophyton floccosum, T.
      tonsurans and T. violaceum. The most common dermatophyte infections included
      tinea corporis, onychomycosis, tinea pedis and tinea faciei. Zoophilic
      dermatophytes were most commonly recovered from children and adolescents with
      tinea capitis, tinea corporis and tinea faciei. Anthropophilic species were
      identified mostly in adults with tinea pedis, onychomycosis and tinea inguinalis.
      During the period studied, we recorded a decline in the rate of M. canis
      infections, while infections produced by T. rubrum increased in frequency.

PMID- 15842335
TI  - Experimental dermatophytosis in calves caused by Trichophyton verrucosum culture.
AB  - Microconidia suspension of Trichophyton verrucosum virulent culture isolated
      originally from the mycotic lesions of cattle was inoculated epicutaneously to
      calves in various doses. Four application methods were selected, namely, onto the
      sheared and gently scarified skin, onto the sheared and non-scarified skin, onto
      the non-sheared and gently scarified skin, and onto the non-sheared and non
      scarified skin. The inoculated area was 10 x 10 cm for all cases mentioned. When
      the application was performed onto the sheared and scarified skin, at least
      18,000 microconidia of T. verrucosum per one animal had to be used to induce the
      mycotic disease in 100% of animals. This value was 10 times higher when the
      application was performed onto the non-sheared and scarified skin, 100 times
      higher in the case of the sheared and non-scarified skin and 1,000 times higher
      in the case of the non-sheared and non-scarified skin. The minimum infectious
      dose still capable of inducing dermatophytosis was 180 microconidia per 100 cm(2)
      of the scarified skin, 18,000 microconidia per 100 cm(2) of the sheared and non
      scarified skin, and 180,000 microconidia per 100 cm(2) of the non-sheared and non
      scarified skin.

PMID- 15842336
TI  - Candidal overgrowth in diabetic patients: potential predisposing factors.
AB  - This study was designed to investigate the potential factors that influence the
      prevalence of the oral carriage of Candida species in patients with type II
      diabetes mellitus. One hundred and twenty-eight diabetic patients (68 males and
      60 females, mean age 54 +/- 7 years) were sequentially enrolled along with 84 (44
      males and 40 females mean age 52 +/- 8 years) healthy subjects. Samples were
      obtained by swabbing the oral mucosa of all participants. Yeast isolates were
      identified by germ tube test, with API 32 ID system, and by chlamydospore
      production on 'cornmeal' Tween-80 agar. Candida spp. was recovered from the oral
      cavity of 64% of the diabetic group, in contrast to 40% of the control group.
      Candida albicans was the most frequently isolated species in both groups.
      Potential etiologic factors such as xerostomia, dentures, age, gender and
      diabetes on oral carriage of Candida spp. were evaluated. The oral carriage of
      Candida spp. was significantly higher in 'diabetic' patients compared with the
      healthy subjects but it seems that parameters such as xerostomia, dentures, age,
      gender and glycemic control cannot be directly associated with Candida growth in
      the oral cavity in the presence of diabetes.

PMID- 15842337
TI  - Detection of Candida dubliniensis in oropharyngeal samples of Turkish HIV
      positive patients.
AB  - The incidence of Candida dubliniensis in immunocomprimised patients in Turkey has
      not yet been determined. In this study the presence of C. dubliniensis in oral
      rinse samples of human immunodeficiency virus (HIV)-positive patients and healthy
      controls were investigated. Phenotypic tests like inability of growth at 45
      degrees C, colony formation on Staib agar, intracellular beta-D-glucosidase
      activity, carbohydrate assimilation profiles and polymerase chain reaction with
      species-specific primers (DUBF and DUBR) were carried out for differentiation of
      C. dubliniensis. Of the 35 patients, four (11.4%) had C.dubliniensis in their
      oral cavity. Antifungal susceptibility testing of these C. dubliniensis isolates
      showed fluconazole MICs ranging from <0.06 to 32 microg ml(-1) and amphotericin B
      from <0.06 to 0.25 microg ml(-1). One isolate was dose-dependently susceptible to
      fluconazole (32 microg ml(-1)). This study demonstrates C. dubliniensis in HIV
      positive patients from Turkey.

PMID- 15842338
TI  - Nine male cases of tinea genitalis.
AB  - Nine cases of tinea genitalis observed in Siena and Terni (Italy) between 1988
      and 2003 are reported because of their infrequency. The patients were males
      ranging in age from 23 to 45 years. The lesions, situated on the penis, glans and
      scrotum, were preceded by dermatophytosis in other sites (groin five cases; feet
      two cases; toenails two cases; hands in one; beard in another). Mycological
      examination consisting of direct microscopy and culture led to isolation of
      Trichophyton rubrum in five cases, Epidermophyton floccosum in two and T.
      mentagrophytes var. interdigitalis in the others. Clinical diagnosis is not
      always easy. In three cases the lesions had been misdiagnosed as eczema.

PMID- 15842339
TI  - Comparison of in vitro activities of antifungal drugs and ethanolic extract of
      propolis against Trichophyton rubrum and T. mentagrophytes by using a
      microdilution assay.
AB  - The in vitro activities of propolis against 29 strains of dermatophytes were
      compared with those of terbinafine, itraconazole, ketoconazole, and fluconazole.
      Minimal inhibitory concentrations (MICs) were determined according to a National
      Committee for Clinical Laboratory Standards broth microdilution method. Among the
      systemic antifungals tested, terbinafine was the most potent. Propolis showed
      important antifungal activity and it merits further investigation as a
      potentially useful agent for the treatment of dermatophytosis.

PMID- 15842340
TI  - Detection of Candida dubliniensis in oropharyngeal samples from human
      immunodeficiency virus infected and non-infected patients and in a yeast culture
      collection.
AB  - The incidence of Candida dubliniensis in oropharyngeal swabs of 132 human
      immunodeficiency virus (HIV)-positive and 89 HIV-negative patients was
      determined. The samples were plated onto CHROMagar Candida medium and 82 strains,
      presumptively identified as C. albicans or C. dubliniensis, were further
      investigated (temperature test, chlamydoconidia production, specific primer PCR).
      In addition, 487 collection strains (isolated from clinical samples and
      previously identified as C. albicans on the basis of a positive germ tube test)
      were screened in order to identify C. dubliniensis isolates. Two C. dubliniensis
      strains were isolated from two HIV-positive patients without oral candidiasis.
      Candida dubliniensis was not isolated from 89 HIV-negative patients nor was it
      identified among the collection strains.

PMID- 15842341
TI  - Fatal Blastoschizomyces capitatus sepsis in a neutropenic patient with acute
      myeloid leukemia: first documented case from Greece.
AB  - Blastoschizomyces capitatus (formerly known as Geotrichum capitatum and
      Trichosporon capitatum) is a rare, yet an emerging, cause of invasive infections
      in immunosuppressed patients. Profound and prolonged neutropenia is the crucial
      predisposing factor for this yeast infection. Blastoschizomyces capitatus was
      isolated from peripheral blood cultures of a profoundly neutropenic patient with
      acute myeloid leukemia (M2 FAB). Despite administration of antifungal
      chemotherapy with liposomal amphotericin B at 4.5 mg kg(-1) daily, the patient
      succumbed 4 days after initiation of treatment. Infections attributed to B.
      capitatus have generally a poor prognosis, although the yeast shows in vitro
      susceptibility to antifungal agents. Low flucytosine, caspofungin acetate,
      voriconazole and amphotericin B minimum inhibitory concentration values were also
      recorded with our isolate. The clinical relevance of the in vitro susceptibility
      testing against the isolate and the current antifungal chemotherapy regimens
      against B. capitatus systemic infections are discussed.

PMID- 15842342
TI  - A case of chromomycosis caused by Fonsecaea pedrosoi and a review of reported
      cases of dematiaceous fungal infection in Japan.
AB  - We report a case of chromomycosis caused by Fonsecaea pedrosoi that developed in
      the left buttock of a 63-year-old female farmer. About 4 years ago, the patient
      developed erythema in the left buttock, which gradually spread. At the first
      consultation, we noted a well-defined, red-brown, infiltrated erythematous plaque
      (8 x 6 cm). Histopathological examination revealed a granulomatous lesion,
      containing sclerotic cells, associated with giant cells in the upper dermis. The
      causative fungus was difficult to identify due to low conidiogenesis, but was
      eventually identified by slide culture as F. pedrosoi. Excision and skin graft
      were performed, and no recurrence has been observed after 2 years. In Japan, 212
      cases of dematiaceous fungal infection were reported in the period from 1982 to
      2001. The causative fungus was F. pedrosoi in the majority of cases (126/212;
      66%), followed by Exophiala jeanselmei (36/212; 19%). Similar incidence of
      dematiaceous fungal infection was reported in male and female patients. The upper
      limbs were affected most frequently in both male and female patients. Ten cases
      were associated with visceral lesions.

PMID- 15842343
TI  - Discovery of alpha2-plasmin inhibitor and its congenital deficiency.

PMID- 15842344
TI  - Fibrinogen measurement to assess the risk of arterial thrombosis in individual
      patients: yes.

PMID- 15842345
TI  - Fibrinogen measurement to assess the risk of arterial thrombosis in individual
      patients: not yet.

PMID- 15842346
TI  - When all else fails to stop massive bleeding from trauma.

PMID- 15842347
TI  - Guidelines for the use of recombinant activated factor VII (rFVIIa) in
      uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task
      Force.
AB  - BACKGROUND: Recombinant activated factor VII (rFVIIa) has been approved by the
      U.S. Food and Drug Administration (FDA) for almost a decade for hemophilic
      patients with inhibitors. Its off-label use as a hemostatic agent in massive
      bleeding caused by a wide array of clinical scenarios is rapidly expanding. While
      evidence-based guidelines exist for rFVIIa treatment in hemophilia, none are
      available for its off-label use. OBJECTIVES: The aim of this study is to develop
      expert recommendations for the use of rFVIIa in patients suffering from
      uncontrolled bleeding (with special emphasis on trauma) until randomized,
      controlled trials allow for the introduction of more established evidence-based
      guidelines. METHODS: A multidisciplinary task force comprising representatives of
      the relevant National Medical Associations, experts from the Medical Corps of the
      Army, Ministry of Health and the Israel National Trauma Advisory Board was
      established in Israel. Recommendations were construed based on the analysis of
      the first 36 multi-trauma patients accumulated in the prospective national
      registry of the use of rFVIIa in trauma, and an extensive literature search
      consisting of published and prepublished controlled animal trials, case reports
      and series. The final consensus guidelines, together with the data of the first
      36 trauma patients treated in Israel, are presented in this article. RESULTS:
      Results of the first 36 trauma patients: The prolonged clotting assays
      [prothrombin time (PT) and partial thromboplastin time (PTT)] shortened
      significantly within minutes following administration of rFVIIa. Cessation of
      bleeding was achieved in 26 of 36 (72%) patients. Acidosis diminished the
      hemostatic effect of the drug, while hypothermia did not affect it. The survival
      rate of 61% (22/36) seems to be favorable compared with published series of
      similar, or less severe, trauma patients (range 30%-57%). CONCLUSIONS: As a
      result of the lack of controlled trials, our guidelines should be considered as
      suggestive rather than conclusive. However, they provide a valuable tool for
      physicians using rFVIIa for the expanding off-label clinical uses.

PMID- 15842348
TI  - The quest for the Holy Grail of tissue factor pathway inhibitor deficiency has
      just begun.

PMID- 15842349
TI  - A novel anticoagulant activity assay of tissue factor pathway inhibitor I (TFPI).
AB  - Tissue factor (TF) pathway inhibitor I (TFPI) is the physiological inhibitor of
      TF-induced blood coagulation. Circulating blood contains full-length TFPI and
      TFPI truncated at the C-terminal end. Previous studies have shown that full
      length TFPI exerts a stronger anticoagulant effect on diluted prothrombin time
      (DPT) than truncated TFPI, and it has been suggested that full-length TFPI is
      biologically more important in vivo. The objective of this study was to develop
      and validate an assay of TFPI anticoagulant activity. TFPI anticoagulant activity
      was assayed using a modified DPT assay. Plasmas were incubated in the absence and
      the presence of TFPI-blocking antibodies. Results were expressed as a ratio with
      the clotting time in the presence of anti-TFPI as the denominator. The ratio was
      normalized against a ratio obtained with a reference plasma. The assay was
      compared with assays of TFPI free antigen, total antigen, and bound TFPI, and
      TFPI chromogenic substrate activity. We performed all tests in 436 healthy
      individuals. The normalized TFPI anticoagulant ratio was strongly associated with
      TFPI free antigen (r = 0.73) but was weakly associated with TFPI chromogenic
      substrate activity (r = 0.46), TFPI total antigen (r = 0.48), and bound TFPI (r =
      0.30). TFPI chromogenic substrate activity was strongly associated with TFPI
      total antigen (r = 0.73). We have developed a novel assay of TFPI anticoagulant
      activity in plasma, which may be considered a functional assay of full-length
      TFPI. Further studies are needed to establish the role of TFPI anticoagulant
      activity for thrombotic disorders.

PMID- 15842350
TI  - Plasma von Willebrand factor levels and surrogates of atherosclerosis.

PMID- 15842351
TI  - Independent association of von Willebrand factor with surrogate markers of
      atherosclerosis in middle-aged asymptomatic subjects.
AB  - Von Willebrand factor (VWF) is considered a reliable marker of endothelial
      damage. Plasma levels of VWF were measured in 857 middle-aged subjects (80.4%
      men) free of clinically overt atherosclerotic disease, in relation to
      cardiovascular risk factors, carotid intima-media thickness (IMT) and
      microalbuminuria, two established surrogate markers of atherosclerosis. There was
      linear trend for the increase of VWF, carotid IMT (p < 0.001) and
      microalbuminuria (p = 0.018). The association between VEF and both markers
      remained statistically significant after adjusting for cardiovascular risk
      factors and inflammatory markers (p < 0.01). In conclusion, VWF was independently
      associated with both structural and functional surrogates of atherosclerosis in
      asymptomatic subjects, thus representing a systemic biomarker of subclinical
      atherosclerosis.

PMID- 15842352
TI  - Atorvastatin affects leukocyte gene expression in dyslipidemia patients: in vivo
      regulation of hemostasis, inflammation and apoptosis.
AB  - BACKGROUND: The beneficial effect of HMG-CoA reductase inhibitors (statins) on
      coronary artery disease has been linked to mechanisms beyond their lipid-lowering
      effect. However the existence of direct, lipid-independent effects of statin in
      humans is still controversial. OBJECTIVE: To investigate the early effect of
      atorvastatin on peripheral blood mononuclear cells (PBMC) in dyslipidemic
      patients using gene arrays. PATIENTS AND METHODS: Eleven male patients with
      primary hyperlipidemia received 20 mg atorvastatin daily for 4 weeks. Blood was
      collected at baseline, 12 h, 36 h, 1 and 4 weeks after the start of treatment.
      RESULTS: Human microarrays containing 12 650 genes were used to study the effect
      of atorvastatin on PBMC gene expression at all time-points. Two hundred and forty
      genes were significantly regulated by atorvastatin treatment, several of which
      are involved in hemostasis, inflammation and other processes critical to
      atherosclerosis. Different patterns of response over time suggested both lipid
      dependent and independent effects of atorvastatin on gene expression.
      CONCLUSIONS: This study demonstrates for the first time that atorvastatin
      regulates gene expression in PBMC in man before changes in the lipid profile are
      detectable in serum. Using blood leukocytes as a pharmacogenomic surrogate, we
      have identified new in vivo targets of atorvastatin treatment.

PMID- 15842353
TI  - The G20210A prothrombin-gene mutation and the plasminogen activator inhibitor
      (PAI-1) 5G/5G genotype are associated with early onset of severe preeclampsia.
AB  - Hereditary risk determinants of venous thrombosis have been reported to be
      associated with severe preeclampsia. So far there are no data to support whether
      these risk determinants are related to the time of onset of severe preeclampsia.
      We used a case-control design, studying 97 women with severe preeclampsia in
      previous pregnancies and 277 normal women, to assess hereditary risk factors of
      venous thrombosis as risk determinants for severe preeclampsia. A case-only
      design comprising solely the 97 women with a history of preeclampsia was used to
      evaluate these risk factors as risk determinants for early onset of severe
      preeclampsia. Using the case-control design, there was no significant risk
      association of the hereditary risk factors with severe preeclampsia [factor V
      Leiden, odds ratio (OR) 0.9, 95% confidence interval (CI) 0.4, 2.2; prothrombin
      mutation, OR 1.9, 95% CI 0.5, 7.0; methylentetrahydrofolate reductase 677TT
      genotype, OR 0.8, 95% CI 0.4, 1.8; plasminogen activator inhibitor (PAI-1) 4G/4G
      genotype, OR 1.2, 95% CI 0.7, 2.1; PAI-1 5G/5G genotype, OR 1.0, 95% CI 0.5,
      1.8]. However, the onset of severe preeclampsia was significantly earlier in
      women with the G20210A prothrombin gene mutation (24.5 weeks vs. 30.1 weeks, P =
      0.046) and in women with the PAI-1 5G/5G genotype (25.7 weeks vs. 30.8 weeks, P =
      0.024). Hereditary risk factors for venous thrombosis do not predispose for
      severe preeclampsia. However, women who are carriers of the G20210A prothrombin
      gene mutation and the PAI-1 5G/5G genotype are at risk for early onset of severe
      preeclampsia. It appears that these risk factors do not induce the pathomechanism
      but accelerate the course of preeclampsia.

PMID- 15842354
TI  - Definition of major bleeding in clinical investigations of antihemostatic
      medicinal products in non-surgical patients.
AB  - Summary. A variety of definitions of major bleeding have been used in published
      clinical studies, and this diversity adds to the difficulty in comparing data
      between trials and in performing meta-analyses. In the first step towards unified
      definitions of bleeding complications, the definition of major bleeding in non
      surgical patients was discussed at the Control of Anticoagulation Subcommittee of
      the International Society on Thrombosis and Haemostasis. Arising from that
      discussion, a definition was developed that should be applicable to studies with
      all agents that interfere with hemostasis, including anticoagulants, platelet
      function inhibitors and fibrinolytic drugs. The definition and the text that
      follows have been reviewed and approved by the cochairs of the subcommittee and
      the revised version is published here. The intention is to also seek approval of
      this definition from the regulatory authorities.

PMID- 15842355
TI  - Clinical outcome of patients with venous thromboembolism and recent major
      bleeding: findings from a prospective registry (RIETE).
AB  - BACKGROUND: Patients who have experienced a recent major bleeding episode are
      usually excluded from clinical studies of venous thromboembolism (VTE) treatment.
      Therefore, recommendations based on evidence from clinical trials may not be
      suitable for these patients. The Registro Informatizado de la Enfermedad
      TromboEmbolica (RIETE) is a multicenter, observational registry designed to
      gather and analyze data on VTE treatment practices and clinical outcomes in
      patients with acute VTE. OBJECTIVES: The aim of this analysis was to study
      outcomes of patients with VTE who had experienced recent major bleeding (< 30
      days prior to VTE diagnosis). METHODS: Patients with objectively confirmed
      symptomatic acute VTE are consecutively enrolled into the RIETE registry. Patient
      characteristics, details of antithrombotic therapy, and clinical outcomes at 3
      months were recorded. RESULTS: Of 6361 patients enrolled up to January 2004, 170
      (2.7%) had experienced recent major bleeding: 69 (40.6%) gastrointestinal tract,
      60 (35.3%) intracranial, 41 (24.1%) other. The incidences of major bleeding
      (4.1%) and recurrent pulmonary embolism (PE) (2.4%) were significantly higher in
      patients with recent major bleeding. Among them, patients with cancer had an
      increased incidence of major bleeding [odds ratio (OR) 10.0, 95% confidence
      interval (CI) 2.3, 50; P < 0.001] and fatal PE (OR 4.1, 95% CI 0.98, 17; P <
      0.05). CONCLUSIONS: Patients with VTE and recent major bleeding prior to VTE
      diagnosis (2.7% of total enrolled patients) had poorer clinical outcomes compared
      with those who had not experienced recent major bleeding. In patients who had
      recent major bleeding prior to enrollment, those with cancer had a poorer
      clinical outcome than those without cancer.

PMID- 15842356
TI  - Thrombomodulin gene polymorphisms or haplotypes as potential risk factors for
      venous thromboembolism: a population-based case-control study.
AB  - Dysfunction of the protein C anticoagulant system is associated with venous
      thromboembolism (VTE) and thrombomodulin (TM) is a critical cofactor within the
      protein C system. The aim of this study was to test the hypotheses that
      polymorphisms or haplotypes within the TM gene are common risk factors for VTE.
      We screened the TM putative promoter, exon and 3'-untranslated region for
      sequence variations in a random sample (n = 266) of consecutive idiopathic,
      objectively confirmed non-Olmsted County VTE patients referred to the Mayo
      Clinic. We then genotyped a sample of Olmsted County, MN residents with a first
      lifetime, objectively confirmed VTE in the 25-year period, 1966-90 (n = 223), and
      a sample of Olmsted County residents without VTE (n = 237) for polymorphisms
      either discovered in the screening population or previously published, and tested
      for an association of VTE with TM genotype or haplotypes using unconditional
      logistic regression and generalized linear models, respectively. We also
      genotyped these Olmsted County cases and controls at 20 'null' genetic maker loci
      and tested for population admixture. Nine novel and three previously described
      mutations were identified in the screening population. Mutations within the TM
      promoter, EGF(1-5), serine/threonine-rich, transmembrane, and cytoplasm regions
      were absent or uncommon. TM845G-->A (Ala25Thr; lectin region), TM2136T-->C
      (Ala455Val; EGF(6) region), TM2470C deletion (3'-untranslated region), and 4363A-
      >G (3'-flanking region) were more common, but were not associated with VTE by
      genotype or haplotype. Null genetic marker allele frequencies did not differ
      significantly among cases and controls. We conclude that polymorphisms or
      haplotypes within the TM gene are not common risk factors for incident VTE.

PMID- 15842357
TI  - Liver histology of an afibrinogenemic patient with the Bbeta-L353R mutation
      showing no evidence of hepatic endoplasmic reticulum storage disease (ERSD);
      comparative study in COS-1 cells of the intracellular processing of the Bbeta
      L353R fibrinogen vs. the ERSD-associated gamma-G284R mutant.
AB  - BACKGROUND: Type I fibrinogen deficiencies (hypofibrinogenemia and
      afibrinogenemia) are rare congenital disorders characterized by low or
      unmeasurable plasma fibrinogen antigen levels. Their genetic bases are
      represented by mutations within the three fibrinogen genes. Among the 11 reported
      missense mutations, a few have been characterized by expression studies and found
      to have an impaired fibrinogen assembly and/or secretion. Histopathological
      analyses were previously reported in two hypofibrinogenemic cases with
      discernible hepatic disease, revealing that both underlying mutations (gamma
      Gly284Arg and gamma-Arg375Trp) were associated with hepatic fibrinogen
      endoplasmic reticulum storage disease (ERSD). OBJECTIVE: The objective of this
      study was to investigate the liver histology in an afibrinogenemic patient,
      homozygous for the Bbeta-Leu353Arg mutation, and to study the intracellular
      processing of the mutant protein. PATIENTS AND METHODS: Liver histology was
      evaluated by light microscopy, electron microscopy and immunocytochemistry.
      Intracellular processing of mutant fibrinogen was analyzed by pulse-chase
      labeling and immunoprecipitation experiments. Messenger RNA levels were
      determined by real-time reverse transcription-polymerase chain reaction (RT-PCR).
      RESULTS: The histopathological characterization of the liver showed no signs of
      fibrinogen accumulation, a difference from the previously reported findings in
      two hypofibrinogenemic kindreds with ERSD. To evaluate whether the Bbeta
      Leu353Arg mutation and the ERSD-associated gamma-Gly284Arg mutation affected
      intracellular fibrinogen trafficking differently, both mutant proteins were
      expressed in COS-1 cells. Bbeta-Leu353Arg led to a more severe secretion defect,
      but no differences that could explain phenotype-genotype correlation were found
      in the intracellular processing. Endoglycosidase-H analysis demonstrated a
      secretion block before translocation to the Golgi medial stacks. Real-time RT-PCR
      studies showed normal levels of the Bbeta mRNA in the patient's liver.
      CONCLUSIONS: The results confirm that Bbeta-Leu353Arg is associated with impaired
      fibrinogen secretion, but not with hepatic ERSD.

PMID- 15842358
TI  - Recombinant factor VIIa enhances platelet adhesion and activation under flow
      conditions at normal and reduced platelet count.
AB  - BACKGROUND: Recombinant factor VIIa (rFVIIa), which was developed for treatment
      of inhibitor-complicated hemophilia, appears suitable as prohemostatic agent in
      other clinical disorders including patients with thrombocytopenia. It is
      generally accepted that rFVIIa functions by enhancement of thrombin generation at
      the site of injury. It is, however, unknown if and how this affects platelet
      adhesion and aggregation. OBJECTIVES: To determine the effect of rFVIIa-mediated
      thrombin generation on platelet adhesion and aggregation under flow conditions at
      normal and reduced platelet counts. METHODS: Washed platelets and red cells were
      combined to obtain plasma-free blood with different platelet counts. The
      reconstituted blood was perfused over a collagen- or fibrinogen-coated surface in
      the absence or presence of a thrombin generating system consisting of purified
      coagulation factors rFVIIa, factor (F)X and prothrombin. RESULTS: Addition of
      coagulation factors rFVIIa, FX and prothrombin to washed platelets and red cells
      enhanced platelet adhesion and aggregation to collagen and adhesion and spreading
      to fibrinogen at normal platelet count and at platelet numbers as low as 10 000
      microL(-1). rFVIIa-mediated thrombin generation enhanced the activation state of
      platelets as measured by intracellular calcium fluxes, and enhanced the exposure
      of procoagulant phospholipids as measured by annexin A5 binding. CONCLUSIONS:
      Taken together, increased platelet adhesion and aggregation by rFVIIa-mediated
      thrombin formation may explain the therapeutic effects of rFVIIa in
      thrombocytopenic conditions and in patients with a normal platelet count by (i)
      enhancement of primary hemostasis and (ii) enhancement of procoagulant surface
      leading to elevated fibrin formation.

PMID- 15842359
TI  - Shiga toxin enhances functional tissue factor on human glomerular endothelial
      cells: implications for the pathophysiology of hemolytic uremic syndrome.
AB  - BACKGROUND: The pathogenesis of Shiga toxin (Stx)-mediated childhood hemolytic
      uremic syndrome (HUS) is not fully delineated, although current evidence
      implicates a prothrombotic state. We hypothesized that the tissue factor (TF)
      pathway plays a major role in the pathophysiology of HUS. MATERIALS AND METHODS:
      We measured cell surface TF activity in response to tumor necrosis factor-alpha
      (TNF-alpha) (20 ng mL(-1), 2-144 h), Stx-1 (10(-11) mol L(-1), 4-144 h), or their
      combination (TNF-alpha 22 h and Stx-1 for the last 0.5-4 h of TNF-alpha
      incubation) on human glomerular (microvascular) endothelial cells (HGECs) and
      human umbilical vein (macrovascular) endothelial cells (HUVECs). RESULTS AND
      CONCLUSIONS: We observed that while TNF-alpha caused an increase in cell surface
      TF activity on both cell types, the combination of TNF-alpha and Stx-1
      differentially affected HGECs. On these cells, TF activity was increased further
      by 2.67 +/- 0.38-fold (n = 38, P < 0.001), consistent with our parallel
      observation that Stx-1 binds to HGECs but not to HUVECs. Anti-TF antibody
      abolished functional TF while anti-tissue factor pathway inhibitor antibody
      enhanced TF activity. Stx-1 alone did not induce TF activity on either cell type.
      Measurement of TF antigen levels and quantitative real-time polymerase chain
      reaction demonstrated that exposure to TNF-alpha markedly increased TF protein
      and TF mRNA for HGECs, but the exposure to the combination of TNF-alpha and Stx-1
      did not increase further the amount of either TF protein or TF mRNA. We conclude
      that cytokine-activated HGECs, but not HUVECs, undergo a significant augmentation
      of cell surface TF activity following exposure to Stx, suggesting an important
      role for TF in the coagulopathy observed in HUS.

PMID- 15842360
TI  - SHPS-1 negatively regulates integrin alphaIIbbeta3 function through CD47 without
      disturbing FAK phosphorylation.
AB  - CD47 (integrin-associated protein) serves as a receptor for thrombospondin-1 (TSP
      1) and Src homology 2 domain-containing protein tyrosine phosphatase substrate-1
      (SHPS-1), and the TSP-1/CD47 interaction has been believed to augment integrin
      mediated platelet function. Here, employing SHPS-1-immunoglobulin (Ig) as a
      ligand, we have newly demonstrated that CD47 acts as an inhibitory receptor for
      platelet function. The binding of SHPS-1-Ig was solely mediated by CD47, because
      CD47-deficient platelets failed to bind murine SHPS-1-Ig. The human SHPS-1/CD47
      interaction inhibited the platelet aggregation induced by several kinds of
      agonists at a low concentration. Moreover, human SHPS-1 expressed on the cell
      surface as well as soluble SHPS-1-Ig markedly inhibited the platelet spreading
      on, but not initial adhesion to, immobilized fibrinogen. Again, neither murine
      SHPS-1 expressed on the cell surface nor murine SHPS-1-Ig inhibited the spreading
      of CD47-deficient platelets. We further investigated the tyrosine phosphorylation
      of signaling proteins during platelet spreading on immobilized fibrinogen.
      Unexpectedly, SHPS-1 inhibited alpha(IIb)beta(3)-mediated platelet spreading
      without disturbing focal adhesion kinase (FAK) tyrosine phosphorylation. Further
      examination revealed that SHPS-1 inhibited the tyrosine phosphorylation of alpha
      actinin, a downstream effector of FAK, but not of cortactin. Thus, it is likely
      that the SHPS-1/CD47 interaction inhibits alpha(IIb)beta(3)-mediated outside-in
      signaling by interfering with the downstream pathway of FAK. Taken together, our
      data suggest that SHPS-1 negatively regulates platelet function via CD47,
      especially alpha(IIb)beta(3)-mediated outside-in signaling.

PMID- 15842361
TI  - Provisional criteria for the diagnosis of VWD type 1.

PMID- 15842362
TI  - The use of LMWH in pregnancies at risk: new evidence or perception?

PMID- 15842373
TI  - Plasma von Willebrand factor and arterial aging.

PMID- 15842374
TI  - Theoretical structural explanation for Group I and Group II, type 2A von
      Willebrand disease mutations.

PMID- 15842375
TI  - Evaluation of the von Willebrand factor Y1584C polymorphism as a potential risk
      factor for bleeding in patients receiving anticoagulant treatment with vitamin K
      antagonists.

PMID- 15842376
TI  - Inhibitor to factor VII in severe factor VII deficiency: detection and course of
      the inhibitory response.

PMID- 15842377
TI  - Genetic variation in alcohol dehydrogenase 3 and the decrease of hs-C-reactive
      protein levels by moderate alcohol consumption.

PMID- 15842378
TI  - Factor VII gene polymorphisms are not associated with myocardial infarction in
      young women.

PMID- 15842379
TI  - Absence of Pro475Ser polymorphism in ADAMTS-13 in Caucasians.

PMID- 15842380
TI  - Functional analysis of two polymorphisms in the 3'-UTR of the human prothrombin
      gene.

PMID- 15842381
TI  - Novel missense mutations in two patients with factor XI deficiency (Val271Leu and
      Tyr351Ser) and one patient with combined factor XI and factor IX deficiency
      (Phe349Val).

PMID- 15842382
TI  - Thrombophilia and venous thromboembolism after total hip or knee replacement
      surgery: a systematic review.

PMID- 15842383
TI  - More on: diagnosing pulmonary embolism in pregnancy: rationalizing fetal
      radiation exposure in radiological procedures.

PMID- 15842385
TI  - Thalidomide protects endothelial cells from doxorubicin-induced apoptosis but
      alters cell morphology--a rebuttal.

PMID- 15842387
TI  - Comparative thrombotic event incidence after infusion of recombinant factor VIIa
      versus factor VIII inhibitor bypass activity--a rebuttal.

PMID- 15842389
TI  - Comparative thrombotic event incidence after infusion of recombinant factor VIIa
      vs. factor VIII inhibitor bypass activity--a rebuttal.

PMID- 15842394
TI  - Pruritic urticarial papules and plaques of pregnancy: current status.
AB  - Pruritic urticarial papules and plaques of pregnancy is a common benign
      dermatosis of pregnancy that was described in 1979 as an intensely pruritic
      urticarial cutaneous eruption. This is a well-defined clinical entity that mainly
      occurs in primigravidas in the third trimester, which resolves spontaneously or
      with delivery and is usually responsive to topical treatments. The aetiology of
      PUPPP is obscure. Histology is non-specific, but consistently shows mild
      lymphohistiocytic perivascular inflammatory infiltrate with a variable number of
      eosinophils. Immunofluorescent studies are negative. The maternal and fetal
      prognosis are generally unaffected, and the condition is usually responsive to
      topical corticosteroids and oral antihistamines.

PMID- 15842395
TI  - Modelling skin disease: lessons from the worlds of mathematics, physics and
      computer science.
AB  - Theoretical biology is a field that attempts to understand the complex phenomena
      of life in terms of mathematical and physical principles. Likewise, theoretical
      medicine employs mathematical arguments and models as a methodology in
      approaching the complexities of human disease. Naturally, these concepts can be
      applied to dermatology. There are many possible methods available in the
      theoretical investigation of skin disease. A number of examples are presented
      briefly. These include the mathematical modelling of pattern formation in
      congenital naevi and erythema gyratum repens, an information-theoretic approach
      to the analysis of genetic networks in autoimmunity, and computer simulations of
      early melanoma growth. To conclude, an analogy is drawn between the behaviour of
      well-known physical processes, such as earthquakes, and the spatio-temporal
      evolution of skin disease. Creating models in skin disease can lead to
      predictions that can be investigated experimentally or by observation and offer
      the prospect of unexpected or important insights into pathogenesis.

PMID- 15842396
TI  - Dysplastic naevi: to shave, or not to shave? A retrospective study of the use of
      the shave biopsy technique in the initial management of dysplastic naevi.
AB  - The management of dysplastic naevi is a controversial subject. This study sought
      to assess the usefulness of the shave biopsy technique in the initial management
      of dysplastic naevi, and to demonstrate the advantages over the punch biopsy
      technique. We report a retrospective observational study of histopathology
      specimens examined in one histopathology practice over a 14-month period.
      Patients who had a clinical diagnosis of 'dysplastic naevus', which had initially
      been biopsied using either a shave or punch biopsy, and then followed up with a
      full-thickness elliptical excision, were included in the study. Histopathological
      concordance between the shave and punch biopsy specimens and their respective
      follow-up elliptical excisions was compared. We found that 21 of 22 (95.5%) shave
      biopsies were concordant with their respective excision specimens, and that 29 of
      41 (70.7%) punch biopsies were concordant with their respective elliptical
      excision specimens. Of the shave biopsy specimens reviewed, 66% showed that the
      dysplastic naevi were completely excised with the initial biopsy, compared with
      21.2% of the punch biopsy specimens. These findings confirm that shave biopsies
      provide accurate diagnostic information in the assessment of dysplastic naevi.
      Shave biopsies enable the entire lesion to be submitted for histopathological
      assessment, improving the chances of an accurate diagnosis.

PMID- 15842397
TI  - Liposuction for axillary hyperhidrosis.
AB  - Excessive axillary sweating is a common problem for which many patients
      frequently seek dermatological advice. The removal of axillary sweat glands using
      liposuction with tumescent anaesthesia in an outpatient setting is a relatively
      short and simple procedure with few complications, as seen in this case series.
      We present 10 patients treated with axillary liposuction under tumescent
      anaesthesia. Of the 10 patients treated, four relapsed with axillary
      hyperhidrosis and required additional liposuction to the same area. The longest
      time to relapse was 15 months, with 4 months being the shortest time. Six
      patients have not required additional liposuction, with 7 years being the longest
      time of remission. The complications reported were bruising in the axillae of two
      patients and relapse of hyperhidrosis in four patients.

PMID- 15842398
TI  - Cutaneous leishmaniasis in Afghani refugees.
AB  - Four Afghani refugees with cutaneous leishmaniasis presented to the dermatology
      clinic at the Women's and Children's Hospital in Adelaide. Three of the patients
      had biopsy-proven cutaneous leishmaniasis that was treated initially with topical
      and then oral ketoconazole, without success. Intralesional sodium stibogluconate
      was then used for these patients with good results. The fourth patient had
      several plaques of biopsy-proven cutaneous leishmaniasis, for which cryotherapy
      was used. This was quite efficacious; however, a small area of recurrence
      required re-treatment. Leishmaniasis is rarely seen in Australia, but an index of
      suspicion is warranted when treating persons with typical clinical features who
      are from endemic regions.

PMID- 15842399
TI  - Papular eruption on a tattoo: a case of primary inoculation tuberculosis.
AB  - The pathogenesis of inoculation cutaneous tuberculosis requires a break in the
      skin, through minor abrasions or injury, allowing the entry of tubercle bacilli.
      We report a 33-year-old man who presented with erythematous papules over a tattoo
      on the right upper arm, 1 month after undergoing a tattoo procedure. Histology
      and cultures revealed infection with Mycobacterium tuberculosis. He was started
      on a 9-month course of antituberculous medication and 3 months after initiation
      of the drugs all the papules had subsided. He has since completed the course of
      therapy and there has been no recurrence 1 year after treatment was started.

PMID- 15842400
TI  - Rhinophyma treated with kilovoltage photons.
AB  - A 72-year-old retired truck driver presented with a 10-year history of rhinophyma
      and was successfully treated with 90-kV photons to a total dose of 40 Gy in 20
      daily fractions. A brief discussion of radiotherapy in the treatment of
      rhinophyma follows.

PMID- 15842401
TI  - Occupational allergic contact dermatitis to bisphenol F epoxy resin.
AB  - A 30-year-old man presented with eyelid dermatitis and was diagnosed with
      occupational allergic contact dermatitis to an epoxy resin based on the monomer
      diglycidyl ether of bisphenol F. He did not react to the standard epoxy resin
      based on bisphenol A, but reacted to a diluted sample of epoxy resin taken from
      his workplace, an adhesives manufacturing plant. The diagnosis would not have
      been made had he not brought samples from work, which were patch tested after
      appropriate dilution. The material safety data sheet provided additional evidence
      that the epoxy was not based on bisphenol A. The patient's symptoms subsided
      after avoidance of the identified product.

PMID- 15842402
TI  - Rheumatoid nodules without arthritis.
AB  - A 53-year-old man presented with firm, non-tender subcutaneous nodules overlying
      his hands and elbows. These had been progressive in number and size over 7 years.
      Rheumatoid factor was negative but a biopsy was consistent with rheumatoid
      nodules. He has never had any joint symptoms and remains otherwise asymptomatic.
      Examination is unremarkable except for the nodules described. We believe this man
      has rheumatoid nodules with no evidence of arthritis.

PMID- 15842403
TI  - Blastomycosis-like pyoderma: successful treatment with low-dose acitretin.
AB  - Blastomycosis-like pyoderma typically presents as verrucous plaque(s) with a
      purulent discharge through multiple sinuses. Two patients with blastomycosis-like
      pyoderma developing on significantly sun-damaged skin are presented: an 84-year
      old man with multiple painful nodules and plaques, and a 92-year-old woman with a
      solitary plaque on the left calf. Histopathology showed pseudoepitheliomatous
      hyperplasia with dermal foci of suppuration. Staphylococcus aureus was isolated
      from a biopsy specimen in the first patient, whereas the latter patient had
      Prevotella and Corynebacterium species. Investigations for fungi and mycobacteria
      yielded negative results. These microbiological findings further supported the
      clinicopathological diagnosis. Both patients failed to respond to oral
      doxycycline despite the in vitro susceptibility of the organisms. Treatment with
      low-dose oral acitretin was successful in both patients after 3-4 months.

PMID- 15842404
TI  - Sulfasalazine and dermatitis herpetiformis.
AB  - Dermatitis herpetiformis that is unable to be controlled using dapsone and a
      gluten-free diet presents a therapeutic challenge. Three cases that responded
      well to sulfasalazine are presented. Two cases, who were unable to tolerate
      dapsone, had a rapid response to sulfasalazine, without apparent side-effects.
      The third case with dapsone-responsive blistering dermatoses, presumed to be
      dermatitis herpetiformis on the basis of serology, showed an excellent clinical
      response to sulfasalazine, but after 6 weeks of therapy had to cease it because
      of side-effects. Sulfasalazine is metabolized variably to sulfapyridine, a
      sulphonamide known to be an effective therapy for dermatitis herpetiformis but no
      longer available. Sulfasalazine should be considered as a management option for
      dermatitis herpetiformis.

PMID- 15842405
TI  - Photo-onycholysis due to sparfloxacin.
AB  - This paper describes a case of sparfloxacin-induced photodermatitis associated
      with photo-onycholysis in a 36-year-old man. He was being treated with
      sparfloxacin, streptomycin, ethambutol and pyrazinamide for pulmonary
      tuberculosis. He developed an exaggerated sunburn-like rash over the face and the
      dorsa of hands and feet, and painful onycholysis of finger- and toe-nails.
      Withdrawal of sparfloxacin resulted in resolution of the skin rash and nail
      tenderness.

PMID- 15842406
TI  - Gianotti-Crosti syndrome in an adult following recent Mycoplasma pneumoniae
      infection.
AB  - A 44-year-old insulin-dependant diabetic woman presented with a pruritic papular
      eruption involving her hands, forearms and elbows. One week prior to the
      eruption, the patient had an upper respiratory tract infection and had taken oral
      ibuprofen 400 mg q.i.d. p.r.n. Skin biopsy revealed histological features
      consistent with Gianotti-Crosti syndrome. Serology was consistent with recent
      Mycoplasma pneumoniae infection and past Epstein-Barr viral infection. Her liver
      function tests were deranged and serum protein electrophoresis showed two sharp
      discrete monoclonal immunoglobulin bands. The eruption resolved completely 15
      days after onset. Her serum protein studies and liver function tests subsequently
      normalized and she had no recurrences of her cutaneous eruption. It was concluded
      that the patient had Gianotti-Crosti syndrome associated with Mycoplasma
      pneumoniae infection.

PMID- 15842407
TI  - Recurrent herpes simplex virus type 2 infection of the hand complicated by
      persistent lymphoedema.
AB  - A 33-year-old, immunocompetent woman had recurrent herpes simplex virus
      reactivation of the right hand presenting with a cellulitis-like picture. She
      continued to have monthly debilitating recrudescences for more than 3 years until
      an adequate dosage of prophylactic antiviral therapy was achieved. After 2 years
      of repeated episodes she had chronic dull pain and developed persistent acquired
      lymphoedema of the left hand and forearm, which is an extremely rare
      complication. This case highlights the need for herpes simplex infection of the
      hand to be included in the differential diagnosis of bacterial cellulitis in
      order for appropriate and prompt therapy to be achieved.

PMID- 15842408
TI  - Atrophic dermatofibrosarcoma protuberans.
AB  - A 48-year-old woman presented with a 20-year history of an asymptomatic depressed
      atrophic plaque on the abdomen. Five years earlier a punch biopsy of the same
      lesion had been carried out and a diagnosis of dermatofibroma was made. She was
      reassured and discharged. Further consultation was sought due to extension and
      thickening of the lesion. Re-examination of the initial and new incisional biopsy
      specimens, along with histochemical staining for CD34, established the diagnosis
      of atrophic dermatofibrosarcoma protuberans. A wide local excision was carried
      out. There has been no recurrence at 9 months of follow up.

PMID- 15842409
TI  - Grzybowski's generalized eruptive keratoacanthoma: remission with
      cyclophosphamide.
AB  - A 57-year-old woman presented with intensely pruritic generalized eruptive
      keratoacanthomas affecting cutaneous and mucosal surfaces (Grzybowski syndrome).
      She derived marginal benefit from anti-pruritic agents, acitretin and
      methotrexate. However, cyclophosphamide 100 mg daily for 1 month followed by 3
      months at 200 mg daily resulted in remarkable improvement and eventual remission
      without further treatment. The disease resulted in severe ectropion of upper and
      lower eyelids bilaterally. Two years after the onset of her disease, the lower
      lid ectropions were repaired using skin grafting. There was no evidence for
      papillomavirus infection.

PMID- 15842410
TI  - Rare complication of Q fever vaccination.
AB  - A 32-year-old woman with a past history of malignant melanoma presented with a
      lump in the upper left arm that was excised. Histological examination revealed a
      granulomatous dermatitis and panniculitis that proved to be a rare reaction to Q
      fever vaccination.

PMID- 15842412
TI  - Determinants of capacious memory: a process-dissociation and experiential
      approach.
AB  - The aim of this study is to delineate some important circumstances where
      exceptionally good memory performance, or capacious memory occurs. A further aim
      is to study memory processes involved in this memory phenomenon. In a first
      experiment, participants looked through two series of pictures differing in
      number and were evaluated in two-alternative forced-choice and yes-no recognition
      memory tasks combined in a process-dissociation procedure. Moreover, participants
      were asked to provide remember and know responses to tap recollective experience.
      The results as to forced-choice recognition task accuracy and according to
      process-dissociation procedure estimates were replicated in a second experiment
      with a more intrinsic contextual manipulation, and in a third, forgetting
      experiment. In addition to replicating previous findings, the results show (a)
      that capacious memory is associated with strong feelings of recollection; and (b)
      that familiarity (in terms of the process-dissociation framework) contributes to
      this phenomenon.

PMID- 15842413
TI  - Antecedent reactivation by surface and deep anaphora in Norwegian.
AB  - Anaphora are expressions in language that depend on other linguistic entities for
      their full meaning. They can furthermore be divided into two types according to
      the level of representation where they find their antecedents: Surface anaphora,
      which resolve their reference at the sentence representation level, and deep
      anaphora, which resolve their reference at the non-grammatical level of discourse
      representation. The linguistic theory of these two anaphor types, and recent
      findings about processing differences at these two levels, combine to predict
      that surface anaphora should show fast and immediate reactivation of their
      antecedents, whereas deep anaphora should have a slower time course of antecedent
      re-access. These predictions were confirmed with two lexical decision task
      experiments with Norwegian stimuli.

PMID- 15842415
TI  - Different working memory capacity in normal young adults for visual and tactile
      letter recognition task.
AB  - Thirty-nine young adult participants performing the visual and tactile n-back
      working memory task were compared. In the visual task, letters were presented on
      a computer screen and in the tactile task, plastic letters embedded on a board
      were explored tactually. The amount of incorrect responses increased with
      increasing memory load in both tasks, but was significantly lower in the visual
      task. Subgrouping the participants with extreme performances into "skilled" and
      "poor" performers showed that the best performance was found among "skilled"
      visual performers, and the worst one among "poor" tactile performers. There was
      more interindividual variation among tactile than visual performance. We conclude
      that tactile working memory capacity, measured here by letter recognition and
      letter memory, is generally more limited and shows more variability than visual
      memory in normal sighted participants.

PMID- 15842414
TI  - Influence of seasonally adjusted exposure to cold and darkness on cognitive
      performance in circumpolar residents.
AB  - The effects of seasonally adjusted 24-h exposure to cold and darkness on
      cognitive performance in urban circumpolar residents was assessed in 15 male
      subjects who spent three 24-h periods in a climatic chamber at 65 degrees
      latitude during the winter (January-March) and/or summer (August-September). Each
      subject was exposed to three different environmental conditions in random order:
      (1) 22 degrees C temperature and 500 lx lighting; (2) 10 degrees C temperature
      and 500 lx lighting; and (3) 10 degrees C temperature and 0.5-l lx lighting.
      Accuracy on an addition-subtraction task was significantly greater in the summer
      than in the winter (p= 0.038), while accuracy on a repeated acquisition task was
      significantly greater in the winter than in the summer (p < 0.001). Independent
      of season, exposure to cold and darkness was significantly associated with a
      decline in response time on five cognitive tests, an improvement in accuracy on
      three tests measuring complex cognitive tasks, and a decline in accuracy on two
      tests measuring simple tasks. Increased performance on complex tasks may result
      from increased arousal in response to the combination of cold temperatures and
      dim light characteristic of the winter in urban circumpolar settings.

PMID- 15842416
TI  - The sensory-cognition association in adulthood: Different magnitudes for
      processing speed, inhibition, episodic memory, and false memory?
AB  - One hundred and forty-six participants (age range = 20-80) completed a battery of
      tests designed to measure visual acuity, processing speed, inhibition, episodic
      memory and false memory. The relations between visual acuity and general
      cognitive ability, as well as between visual acuity and the indicators of this
      construct, were evaluated with structural equation modeling. The measurement
      model confirmed that the indicators of the individual cognitive abilities could
      be grouped into a general cognitive functioning factor. However, the relation
      between episodic and false memory was not completely explained by the shared
      association with this general factor. Furthermore, visual acuity predicted
      approximately half of the age-related variance in the general cognition factor.
      Also, the proportion of age-related variance shared with vision was highest in
      inhibition and lowest in false memory. The results are discussed in the light of
      common cause accounts of cognitive aging.

PMID- 15842417
TI  - Orthography as a handicap? A direct comparison of spelling acquisition in Danish
      and Icelandic.
AB  - Spelling of cross-linguistically very similar nonwords was compared in 115 Danish
      and 77 Icelandic children (primarily 3rd and 4th graders). Danish children made
      more errors than Icelandic children on word medial consonant doublets and on word
      initial consonant clusters, even when the groups compared were matched on simpler
      spelling tasks. These results suggest that the acquisition of phonemic encoding
      skills is slower in "deep" orthography such as Danish than in more "transparent"
      orthography such as Icelandic. The effect of orthography was expected for
      consonant doublets because of the relatively more complex sound-letter
      correspondences in Danish. For consonant clusters, however, sound-letter
      correspondences are perfectly regular in both languages. The study thus points to
      the conclusion that even the mastery of regular sound-letter correspondences may
      be delayed in deep orthography.

PMID- 15842418
TI  - Poverty and experiences of social devaluation: a qualitative interview study of
      25 long-standing recipients of social security payments.
AB  - The purpose of this study is to explore experiences of social devaluation among
      people living in poverty. Twenty-five long-standing recipients of social security
      payments living in a city in Norway were interviewed. Most felt that people in
      their environment held low opinions of them regarding issues related to
      personality and moral integrity. Several factors play a role in the formation of
      such beliefs or assumptions: (a) impressions of prevailing views of the social
      category "the poor" and observations concerning devaluation of that category; (b)
      knowledge others are assumed to possess of the respondents' financial
      predicament; (c) perception of own social situation; (d) undesired behavior that
      signals low social status and low esteem; (e) actions by others that signal
      devaluation. Social devaluation is also experienced at the affective level: the
      sense of shame and guilt is widespread.

PMID- 15842419
TI  - An empirical look at the Defense Mechanism Test (DMT): reliability and construct
      validity.
AB  - Although the Defense Mechanism Test (DMT) has been in use for almost half a
      century, there are still quite contradictory views about whether it is a reliable
      instrument, and if so, what it really measures. Thus, based on data from 39
      female students, we first examined DMT inter-coder reliability by analyzing the
      agreement among trained judges in their coding of the same DMT protocols. Second,
      we constructed a "parallel" photographic picture that retained all structural
      characteristic of the original and analyzed DMT parallel-test reliability. Third,
      we examined the construct validity of the DMT by (a) employing three self-report
      defense-mechanism inventories and analyzing the intercorrelations between DMT
      defense scores and corresponding defenses in these instruments, (b) studying the
      relationships between DMT responses and scores on trait and state anxiety, and
      (c) relating DMT-defense scores to measures of self-esteem. The main results
      showed that the DMT can be coded with high reliability by trained coders, that
      the parallel-test reliability is unsatisfactory compared to traditional
      psychometric standards, that there is a certain generalizability in the number of
      perceptual distortions that people display from one picture to another, and that
      the construct validation provided meager empirical evidence for the conclusion
      that the DMT measures what it purports to measure, that is, psychological defense
      mechanisms.

PMID- 15842420
TI  - Visual neglect in the first weeks after a stroke in the right hemisphere.
AB  - The aim of the study was to characterize symptoms of visual neglect among
      patients who recently survived a stroke in the right hemisphere (RH), and to
      contribute to the understanding of change in symptoms during the first months
      after a RH stroke. Thirteen patients with a RH stroke and twenty controls were
      assessed by using standard neglect tests. Five patients were followed up by
      repetitive test sessions during the next four months. To assess more subtle
      symptoms, reaction-time (RT) measures derived from an experimental cue-target
      paradigm were included in the final test session. A high frequency of neglect
      symptoms was documented at the first test session. The changes in performance
      during the first weeks were characterized by a high inter-individual as well as a
      high intra-individual variability. Although the remission rate on standard tests
      was high in the follow-up study, the RT measures indicated sustained symptoms of
      visual extinction in all patients. The long-term implication of the changes of
      neglect symptoms during the first weeks after a stroke and signs of sustained
      symptoms of visual extinction calls for further longitudinal studies including a
      larger group of patients.

PMID- 15842421
TI  - Participation in school environment of children and youth with disabilities: a
      person-oriented approach.
AB  - This study investigated patterns of interrelated positive subject and
      environmental factors related to participation in school activities of pupils
      with different kinds of disabilities. Questionnaires concerning participation
      were collected from 472 pupils with disabilities and their teachers, parents and
      special education consultants. A person-oriented approach with the aim to
      identify patterns of variables related to a high degree of participation of
      pupils with disabilities was used. Cluster-groups were formed based on scores for
      individual subjects on factors identified as important for participation. Groups
      with a high degree of participation were characterized by high scores in autonomy
      and perceived interaction with peers and teachers and an internal locus of
      control. Type and degree of disability did not predict cluster group membership.
      A conclusion is that the outcome participation is better predicted by patterns of
      interrelated positive subject and environmental factors than by type of
      disability or any other single factor.

PMID- 15842422
TI  - Dynamics of ventricular repolarization in patients with dilated cardiomyopathy
      versus healthy subjects.
AB  - BACKGROUND: Patients with impaired left ventricular function have a high risk of
      developing ventricular arrhythmias and sudden death. Among different markers of
      risk, the prolongation and regional heterogeneity of repolarization are of
      increasing interest. However, there are limited data regarding feasibility of
      analyzing repolarization parameters and their dynamics in 24-hour Holter ECG
      recordings. METHODS: Dynamic behavior of repolarization parameters was studied
      with a new automatic algorithm in digital 24-hour Holter recordings of 60 healthy
      subjects and 55 patients with idiopathic dilated cardiomyopathy (IDC).
      Repolarization parameters included the mean value of QT and QTc durations, QT
      dispersion, and peaks of QT duration and QT dispersion above prespecified
      thresholds. RESULTS: In comparison to healthy subjects, patients with IDC had
      lower heart rate variability, longer mean QT and QTc durations, higher content of
      QTc peaks >500 ms, longer QT dispersion and its standard deviation, and a higher
      content of peaks >100 ms of QT dispersion (P < 0.01 for all comparisons). These
      repolarization parameters were significantly higher in IDC patients after
      adjustment for age, sex, and heart rate variability. The parameters of
      repolarization dynamics correlated with SDNN in healthy subjects but not in
      dilated cardiomyopathy patients. CONCLUSIONS: The automatic assessment of
      repolarization parameters in 24-hour digital ECG recordings is feasible and
      differentiates dilated cardiomyopathy patients from healthy subjects. Patients
      with dilated cardiomyopathy have increased QT duration, QT dispersion, and
      increased variability of QT dispersion reflecting variations in T-wave
      morphology, the factors which might predispose them to the development of
      arrhythmic events.

PMID- 15842423
TI  - Increases in P-wave duration and dispersion after hemodialysis are totally (or
      partially) due to the procedure-induced alleviation of the body fluid overload: a
      hypothesis with strong experimental support.
AB  - Increases in the P-wave duration (P-du) and P-wave dispersion (P-d) following
      hemodialysis (HD) are attributed to changes in the electrolytic milieu with HD,
      or are considered to be due to an unknown mechanism. Such changes are thought to
      be proarrhythmic, and thus have potential clinical implications. Increase in the
      amplitude of QRS complexes following HD has been amply documented in the
      literature. Also, recent work linking attenuation/augmentation of amplitude of
      QRS and P-wave complexes in patients with increase/subsequent decrease weights
      due to anasarca peripheral edema/and its alleviation, or before/after
      hemodialysis (HD) suggests that the increase in the P-du and P-d after HD may be
      totally (or partially) mediated by the alleviation of the fluid overload by the
      procedure. This is supported by the decrease/increase in the QRS duration noted
      with anasarca/and its alleviation. To further clarify this issue, and prove or
      refute the above hypothesis, it is recommended that correlations of changes in
      the P-du and P-d with the loss of weight or net fluid dialyzed are carried out,
      in addition to the traditional considerations of electrolytic alterations after
      HD.

PMID- 15842424
TI  - Comparison of the four formulas of adjusting QT interval for the heart rate in
      the middle-aged healthy Turkish men.
AB  - OBJECTIVE: The aim of this study was to evaluate the QT intervals at different
      rest heart rates in healthy middle-aged Turkish men and to compare the known four
      QT adjusting methods for heart rate. METHODS AND RESULTS: The QT intervals were
      measured in electrocardiograms of 210 healthy men (mean age = 35-60 years). A
      curve relating QT intervals and heart rates from 45 to 135 beats/min was
      constructed for study population. Based on the formula of Bazett, Fridericia, and
      Framingham, adjusted QT intervals in these range of heart rates were separately
      estimated. An adjusting nomogram for different heart rates was created using a
      reference value, which was the measured QT interval at heart rate of 60 beats/min
      (QT(No) = QT + correcting number). These four QT correction methods were compared
      with each other. The reference value of QT interval at heart rate of 60 beats/min
      was 382 ms. The relationship between QT and RR interval was linear (r = 0.66, P <
      0.001). Nomogram method corrected QT interval most accurately for all the heart
      rates compared with other three adjusting methods. At heart rates of 60-100
      beats/min, the equation of linear regression was QT = 237 + 0.158 x RR (P <
      0.001). Bazett's formula gave the poorest results at all the heart rates. The
      formulas of Fridericia and Framingham were superior to Bazett's formula; however,
      they overestimated QT interval at heart rate of 60-110 beats/min (P < 0.01). At
      lower rates (<60 beats/min), all methods except nomogram method, underestimated
      QT interval (P = 0.03). CONCLUSION: Among four QT correction formulas, the
      nomogram method provides the most accurately adjusted values of QT interval for
      all the heart rates in healthy men. Bazett's formula fails to adjust the QT
      interval for all the heart rates.

PMID- 15842425
TI  - Extraction of buried P waves from printed electrocardiograms.
AB  - BACKGROUND: Morphologic identification of ectopic P-waves from surface ECGs can
      be challenging, particularly when the P-wave is buried in the QRST wave complex.
      Because ECGs are often available on paper and not digitally, we developed a
      method of subtracting the T-wave from the buried P-wave complex on paper ECGs.
      METHODS: To validate our system, an atrial extrastimulus was introduced during
      and following the T-wave. The ECGs were scanned and then transformed from an
      image format to a digital format. A computer algorithm digitally subtracted a
      QRST with no buried P-wave from one with a buried P-wave, thus resulting in an
      extracted P-wave. The extracted P-waves were compared to the nonburied P-wave by
      determining correlation coefficients and by visual grading by two independent
      reviewers. RESULTS: Visual grading comparing the buried P-wave with the exposed
      paced P-wave was 94%. The median correlation coefficient was 85%. CONCLUSIONS: An
      ectopic atrial P-wave obscured by a coincident QRST wave complex can be
      accurately derived from printed ECG using this PC-based system. Addition of this
      technique to the existing methods may aid in the localization and ablation of
      ectopic atrial foci.

PMID- 15842426
TI  - T-wave abnormalities are a better predictor of cardiovascular mortality than ST
      depression on the resting electrocardiogram.
AB  - BACKGROUND: ST depression and T-wave amplitude abnormalities are known to be
      independent predictors of cardiovascular (CV) death, but a direct comparison
      between them has not been described. METHODS: Analyses were performed on the
      first electrocardiogram (ECG) digitally recorded on 46,950 consecutive patients
      at the Palo Alto Veterans Affairs Medical Center since 1987. Females and patients
      with electrocardiograms exhibiting bundle branch block, left ventricular
      hypertrophy, electronic pacing, diagnostic Q waves, or Wolff-Parkinson-White
      syndrome were excluded, leaving 31,074 male patients for analysis (mean age 55 +/
      14). There were 1878 (6.0%) cardiovascular deaths (mean follow-up of 6 +/- 4
      years). Electrocardiograms were classified using Minnesota code according to the
      degree of ST depression and T-wave abnormality, and the nine possible
      combinations of ST segment and T-wave abnormalities were recoded for analysis.
      RESULTS: The combination of major abnormalities in ST segments and T-waves
      carried the greatest hazard [3.2 (CI 2.7-3.8)]. Minor ST depression combined with
      more severe T-wave abnormalities carried a hazard of 3.1 (CI 2.5-3.7), whereas
      minor T-wave abnormalities combined with more severe ST depression carried a
      hazard of only 1.9 (CI 1.6-2.3). CONCLUSION: While both ST segment depression and
      abnormal T-wave amplitude are clinically important, T-wave abnormalities appear
      to be greater predictors of cardiovascular mortality.

PMID- 15842427
TI  - Magnetocardiogram recordings in a nonshielded environment--reproducibility and
      ischemia detection.
AB  - BACKGROUND: Magnetocardiography (MCG) is a noninvasive technology that measures
      the magnetic field of the heart by superconducting quantum interference devices
      (SQUID) sensors. The novelty of the present system is that the sensors can be
      operated without electromagnetic shielding of the examination room, thus allowing
      the system to be easily installed in the emergency department or chest pain unit.
      Studies in shielded rooms, found that this imaging modality may have better
      sensitivity as compared to ECG in detecting ischemia. We aimed (1) to assess the
      reproducibility, intra-observer, and interobserver interpretation variability and
      (2) to assess the MCG maps in the presence of coronary narrowings. METHODS AND
      RESULTS: All measurements were performed in a nonshielded room. For the first
      part of the study, two MCG maps were recorded in 24 otherwise healthy volunteers
      (age 20-44 years, median 24, 16 male) in an interval ranging from 2 to 48 hours.
      The maps were interpreted using the CardioMag software for contour maps, averaged
      MCG time traces, and waveform morphology of repolarization by two observers
      blinded to each other. The parameters tested had low disagreement between
      repeated measurements. The correlations of the intra-observer and interobserver
      interpretation were excellent. Secondly, MCG maps were obtained in 29 patients
      referred for angiography due to suspected coronary artery disease. Nineteen of
      them had coronary narrowings defined as more than 50%. In this group, 16 (84.2%)
      had abnormal MCG maps as compared to only 5 (26.3%) who had abnormal ECGs (P <
      0.01). CONCLUSIONS: MCG maps can be successfully obtained in a nonshielded room
      and allow feasible, accurate, and reproducible measurements with little intra
      observer and interobserver variability. Ischemic changes in the heart's magnetic
      field may occur before electrical changes. Our pilot data suggests that this
      imaging modality may potentially offer better sensitivity as compared to rest ECG
      in detecting ischemia in a cohort of patients who had coronary narrowings
      identified by angiography.

PMID- 15842428
TI  - Continuous ST-segment monitoring of patients with right bundle branch block and
      suspicion of acute myocardial Infarction.
AB  - BACKGROUND: Patients with right bundle branch block comprise 5-9% of all patients
      with acute myocardial infarction. In spite of this, limited data exist on early
      diagnosis or the usefulness of continuous electrocardiographic monitoring in
      these patients. METHODS: A prospective multicenter study with 14 Swedish coronary
      care units. Patients with right bundle branch block and suspicion of acute
      myocardial infarction with less than 6 hours symptom duration were included. All
      patients were monitored with continuous vectorcardiography for 12-24 hours.
      RESULTS: Seventy-nine patients were included, 43% had acute myocardial
      infarction. Patients with acute myocardial infarction had significantly higher
      initial ST-vector magnitude values (P = 0.0014) compared to patients without
      acute myocardial infarction. Patients with acute myocardial infarction also
      showed gradual regression of ST-vector magnitude over time that was not seen for
      patients without acute myocardial infarction (P = 0.005). ST-vector magnitude
      measured at the J-point differentiated best between patients with and without
      acute myocardial infarction. A cutoff value of 125 microV for initial ST-vector
      magnitude resulted in 55% sensitivity and 87% specificity for the diagnosis of
      acute myocardial infarction. Over time, patients with acute myocardial infarction
      showed greater changes in QRS-vector difference compared to patients without
      acute myocardial infarction (P = 0.052). CONCLUSION: Vectorcardiographic
      monitoring shows good diagnostic abilities for patients with right bundle branch
      block and clinical suspicion of acute myocardial infarction and could be useful
      for continuous monitoring of these patients.

PMID- 15842429
TI  - Individual QT-R-R relationship: average stability over time does not rule out an
      individual residual variability: implication for the assessment of drug effect on
      the QT interval.
AB  - BACKGROUND: Universal QT correction formulae have been shown to under or
      overcorrect the QT interval duration. Individual QT-R-R modeling has been
      proposed as a preferable solution for heart rate correction of QT intervals.
      However, the QT-R-R relationship stability over time needs to be evaluated.
      METHODS: The present report is part of randomized, double-dummy, and placebo
      controlled 4-way crossover phase 1 study (48 healthy volunteers). Each randomized
      period included a run-in placebo day followed the day after by drug
      administration, with moxifloxacin as a positive control for QT interval
      measurement. Digital Holter ECG data were analyzed using the "bin" approach. For
      each period, individual QT-R-R relationship were calculated using two different
      models (linear and parabolic log-log models). RESULTS: The mean intrasubject
      variability for the alpha coefficient of the linear modeling (SDintra = 0.011 +/-
      0.005) reached 28.6 +/- 10.2%. When the parabolic model was considered, the
      SDintra was 0.026 +/- 0.009 for the alpha coefficient. The QT-R-R relationship
      variability was in part related to long-term RR changes (R2 = 30%, P < 0.05).
      However, no significant time effect (ANOVA) was evidenced for QT-R-R
      coefficients. Moxifloxacin significantly increased the alpha coefficient of the
      QT-R-R relationship from 0.07 +/- 0.018 to 0.085 +/- 0.019, P < 0.05 (linear
      model). CONCLUSIONS: The individual QT-R-R relationship shows a residual
      variability in part related to long-term autonomic changes. In addition, the QT-R
      R relationship might be modulated by the drug tested. As a consequence,
      pretherapy QT-R-R relationship obtained in a given patient cannot be used as a
      fingerprint throughout a drug trial.

PMID- 15842430
TI  - Accelerated idioventricular rhythm in the post-thrombolytic era: incidence,
      prognostic implications, and modulating mechanisms after direct percutaneous
      coronary intervention.
AB  - BACKGROUND: In the thrombolytic era, the occurrence of accelerated
      idioventricular rhythm (AIR) has been proposed to be a specific marker for
      successful reperfusion. The incidence, prognostic implications, and potential
      modulating mechanisms of AIR after successful restoration of antegrade flow by
      means of modern reperfusion therapy (i.e., direct percutaneous coronary
      intervention (PCI)) has thus far not been investigated. METHODS: We prospectively
      investigated 125 consecutive patients undergoing direct PCI for a first acute
      myocardial infarction (AMI). The incidence of AIR was determined from 24-hour
      Holter monitoring, initiated prior to PCI. RESULTS: AIR appeared in 19 patients
      (15.2%). There were no significant differences between patients with or without
      AIR regarding baseline clinical characteristics. The incidence of AIR was not
      different between patients with TIMI 2 and 3 flow (13% vs 16%). There were no
      differences in the incidence of major cardiac events within 12-month follow-up in
      patients with and without AIR. Patients with AIR exhibited higher mean R-R
      intervals (mean 24-hour R-R interval: 871.3 +/- 121 vs 796.4 +/- 100 ms, P <
      0.01), higher hourly mean values of heart rate variability (SDNN, 64.7 +/- 26 vs
      49.4 +/- 20 ms, P < 0.01; rMSSD, 29.3 +/- 15 vs 22.0 +/- 12 ms, P < 0.01) and
      lower serum norepinephrine concentrations (60 minute after PCI, 478.9 +/- 357 vs
      649.0 +/- 499 pg/ml, P < 0.05). CONCLUSIONS: Our findings indicate that AIR is an
      nonspecific marker for reperfusion of the infarct-related artery in AMI and thus,
      predate previous observations of the thrombolytic era. Even though, AIR was
      associated with higher tonic vagal tone and lower sympathetic activity, the
      occurrence of AIR had no prognostic impact on the clinical course and was not
      able to discriminate between complete and incomplete reperfusion.

PMID- 15842431
TI  - The value of magnetocardiography in the course of coronary intervention.
AB  - BACKGROUND: The noninvasive detection of restenosis after percutaneous coronary
      intervention (PCI) remains a clinical challenge. Previous studies have shown that
      magnetocardiograms reveal obvious changes in patients with coronary artery
      disease (CAD) and normal electrocardiogram (ECG) at rest. HYPOTHESIS: The present
      study aimed to evaluate the potential of magnetocardiography (MCG) for the
      detection of electrophysiological changes in the course of successful PCI.
      METHODS: Twelve-lead ECG and unshielded four-channel MCG (SQUID AG, Essen,
      Germany) were registered at nine prethoracic sites in 50 patients with CAD (62 +/
      10 years; EF = 76 +/- 11%; registration: before, 24 hours, and 1 month (n = 25)
      after PCI) and 57 normals (51 +/- 9 years). Current density vector (CDV) maps
      were reconstructed within the ST-T interval and classified from category 0
      (normal) to category 4 (grossly abnormal). In both groups and at all registration
      times, the percentage of each category of maps was calculated and compared.
      RESULTS: Most CDV maps of normals were classified as category 0, 1, or 2 compared
      to CAD patients before PCI with most maps of category 3 and 4 (P < 0.0005).
      Twenty-four hours after PCI, more maps were classified as category 2 (P < 0.05)
      and less as category 4 (P < 0.005). One month after PCI the MCG results further
      improved: more maps were classified as category 1 (P < 0.05) and 2 (P < 0.005)
      and less maps as category 4 (P < 0.0001). The ECG remained unchanged in the
      course of PCI. CONCLUSION: Unshielded four-channel MCG reveals obvious changes in
      the course of successful PCI on the basis of CDV map reconstruction during
      repolarization. The method seems to be suitable for the follow-up of patients
      after PCI.

PMID- 15842432
TI  - Identification of optimal electrocardiographic criteria for the diagnosis of
      unrecognized myocardial infarction: a population-based study.
AB  - BACKGROUND: Despite using the same tool (ECG), the proportion of myocardial
      infarctions that goes unrecognized varies from 20% to 60% in population-based
      studies. The reasons for such wide variations have not been studied. We sought to
      evaluate the effect of ECG-MI criteria and study methodology on the prevalence of
      unrecognized myocardial infarction (UMI) and to identify the optimal ECG-MI
      criteria for UMI detection in epidemiologic studies. METHODS: A random population
      based sample of 2042 adults, age > or = 45 years, underwent history, medical
      record abstraction and ECG. Six different ECG-MI criteria and two subjective
      recognized myocardial infarction (RMI) identification criteria, from different
      published studies, were applied to the same survey ECG. The operating test
      characteristics of different criteria were compared with the objective criterion
      standard of a RMI by Gillum criteria. RESULTS: The UMI proportion estimates
      varied from 32% to 61% due to variation in ECG-MI criteria, while keeping the
      study population, MI recognition criteria, and ECG constant. Subjective criteria
      for MI recognition had limited value (positive predictive value of 44-93%) in
      picking up RMI. Depending on the ECG abnormality used to define MI, ECG reading
      had widely varying sensitivity (21-37%; P < 0.0001) with consistently high
      specificity (92-97%) for detection of RMI. CONCLUSIONS: The prevalence estimates
      of UMI vary widely and are strongly dependent on the ECG-MI and MI recognition
      criteria. Future studies of UMI should explicitly recognize this variation and
      select the ECG-MI criteria that match their study aims.

PMID- 15842433
TI  - Pilot study: Noninvasive monitoring of oral flecainide's effects on atrial
      electrophysiology during persistent human atrial fibrillation using the surface
      electrocardiogram.
AB  - BACKGROUND: The relation between flecainide's plasma level and its influence on
      human atrial electrophysiology during acute and maintenance therapy of atrial
      fibrillation (AF) is unknown. Therefore, this study determined flecainide plasma
      levels and atrial fibrillatory rate obtained from the surface ECG during
      initiation and early maintenance of oral flecainide in patients with persistent
      lone AF and assessed their relationship. METHODS AND RESULTS: In 10 patients (5
      males, mean age 63 +/- 14 years, left atrial diameter 46 +/- 3 mm) with
      persistent lone AF, flecainide was administered as a single oral bolus (day 1)
      followed by 200-400 mg/day (days 2-5). The initial 300 mg flecainide bolus
      resulted in therapeutic plasma levels in all patients (range 288-629 ng/ml) with
      no side effects. Flecainide plasma levels increased on day 3 and remained stable
      thereafter. Day 5 plasma levels were lower (508 +/- 135 vs 974 +/- 276 ng/ml, P =
      0.009) in patients with daily mean flecainide doses of 200 mg compared to
      patients with higher maintenance doses. Fibrillatory rate obtained from the
      surface electrocardiogram measuring 378 +/- 17 fpm at baseline was reduced to 270
      +/- 18 fpm (P < 0.001) after the flecainide bolus but remained stable thereafter.
      Fibrillatory rate reduction was independent of flecainide plasma levels or
      clinical variables. CONCLUSION: A 300 mg oral flecainide bolus is associated with
      electrophysiologic effects that are not increased during early maintenance
      therapy in persistent human lone AF. In contrast to drug plasma levels, serial
      analysis of fibrillatory rate allows monitoring of individual drug effects on
      atrial electrophysiology.

PMID- 15842434
TI  - ECG repolarization waves: their genesis and clinical implications.
AB  - The electrocardiographic (ECG) manifestation of ventricular repolarization
      includes J (Osborn), T, and U waves. On the basis of biophysical principles of
      ECG recording, any wave on the body surface ECG represents a coincident voltage
      gradient generated by cellular electrical activity within the heart. The J wave
      is a deflection with a dome that appears on the ECG after the QRS complex. A
      transmural voltage gradient during initial ventricular repolarization, which
      results from the presence of a prominent action potential notch mediated by the
      transient outward potassium current (I(to)) in epicardium but not endocardium, is
      responsible for the registration of the J wave on the ECG. Clinical entities that
      are associated with J waves (the J-wave syndrome) include the early
      repolarization syndrome, the Brugada syndrome and idiopathic ventricular
      fibrillation related to a prominent J wave in the inferior leads. The T wave
      marks the final phase of ventricular repolarization and is a symbol of transmural
      dispersion of repolarization (TDR) in the ventricles. An excessively prolonged QT
      interval with enhanced TDR predisposes people to develop torsade de pointes. The
      malignant "R-on-T" phenomenon, i.e., an extrasystole that originates on the
      preceding T wave, is due to transmural propagation of phase 2 reentry or phase 2
      early afterdepolarization. A pathological "U" wave as seen with hypokalemia is
      the consequence of electrical interaction among ventricular myocardial layers at
      action potential phase 3 of which repolarization slows. A physiological U wave is
      thought to be due to delayed repolarization of the Purkinje system.

PMID- 15842435
TI  - Reperfusion associated cardioversion of atrial fibrillation in acute myocardial
      infarction.

PMID- 15842436
TI  - The history of clinical Holter Monitoring.

PMID- 15842437
TI  - Electrocardiographic follow-up of biventricular pacemakers.
AB  - Multisite pacing for the treatment of heart failure has added a new dimension to
      the electrocardiographic evaluation of device function. During left ventricular
      (LV) pacing from the appropriate site in the coronary venous system, a correctly
      positioned lead V1 registers a right bundle branch block pattern with few
      exceptions. During biventricular stimulation associated with right ventricular
      (RV) apical pacing, the QRS is often positive in lead V1. The frontal plane QRS
      axis is usually in the right superior quadrant and occasionally in the left
      superior quadrant. Barring incorrect placement of lead V1 (too high on the
      chest), lack of LV capture, LV lead displacement or marked latency (exit block or
      delay from the stimulation site), ventricular fusion with the spontaneous QRS
      complex, a negative QRS complex in lead V1 during biventricular pacing involving
      the RV apex probably reflects different activation of an heterogeneous
      biventricular substrate (ischemia, scar, His-Purkinje participation in view of
      the varying patterns of LV activation in spontaneous left bundle branch block)
      and does not necessarily indicate a poor (electrical or mechanical) contribution
      from LV stimulation. In this situation, it is imperative to rule out the presence
      of coronary venous pacing via the middle cardiac vein or even unintended
      placement of two leads in the RV. During biventricular pacing with the RV lead in
      the outflow tract, the paced QRS in lead V1 is often negative and the frontal
      plane paced QRS axis is often directed to the right inferior quadrant (right axis
      deviation). In patients with sinus rhythm and a relatively short PR interval,
      ventricular fusion with competing native conduction during biventricular pacing
      may cause misinterpretation of the ECG because narrowing of the paced QRS complex
      simulates appropriate biventricular capture. This represents a common pitfall in
      device follow-up. Elimination of ventricular fusion by shortening the AV delay,
      is often associated with clinical improvement. Anodal stimulation may complicate
      threshold testing and should not be misinterpreted as pacemaker malfunction. One
      must be cognizant of the various disturbances that can disrupt 1:1 atrial
      tracking and cause loss of ventricular resynchronization. (1) Upper rate
      response. The upper rate response of biventricular pacemakers differs from the
      traditional Wenckebach upper rate response of conventional antibradycardia
      pacemakers because heart failure patients generally do not have sinus bradycardia
      or AV junctional conduction delay. The programmed upper rate should be
      sufficiently fast to avoid loss of resynchronization in situations associated
      with sinus tachycardia. (2) Below the programmed upper rate. This may be caused
      by a variety of events (especially ventricular premature complexes and favored by
      the presence of first-degree AV block) that alter the timing of sensed and paced
      events. In such cases, atrial events become trapped into the postventricular
      atrial refractory period at atrial rates below the programmed upper rate in the
      presence of spontaneous AV conduction. Algorithms are available to restore
      resynchronization by automatic temporary abbreviation of the postventricular
      atrial refractory period.

PMID- 15842438
TI  - QT dynamics and variability.
AB  - Repolarization dynamics and variability are of increasing interest as Holter
      derived parameters reflecting changes in myocardial vulnerability and
      contributing to increased risk of arrhythmic events and sudden death.
      Repolarization dynamics is usually defined as phenomenon describing and
      quantifying QT adaptation to changing heart rate. The analysis of QT-R-R slopes
      in long ECG recordings is one of the ways to evaluate repolarization dynamics.
      Increased QT-R-R slopes are frequently observed in patients at risk for cardiac
      death and arrhythmic events: postinfarction patients, long QT syndrome patients,
      patients with nonischemic cardiomyopathy as well as in patients taking drugs
      affecting repolarization. QT variability reflects beat-to-beat changes in
      repolarization duration and morphology and such changes can be quantified using a
      number of algorithms currently in various phases of development and validation.
      Increased QT variability is observed in several conditions with increased risk of
      arrhythmias. Recent data from MADIT II indicate that increased QT variability is
      a powerful predictor of arrhythmic events in postinfarction patients with left
      ventricular dysfunction. More studies are needed to determine further the
      potential clinical usefulness for diagnosing patients and for risk stratification
      purposes using both QT dynamics and QT variability methods, and compare these
      methods with exercise-induced T wave alternans.

PMID- 15842439
TI  - ST-segment analysis in ambulatory ECG (AECG or Holter) monitoring in patients
      with coronary artery disease: clinical significance and analytic techniques.

PMID- 15842440
TI  - Speaking out in uncertain times.

PMID- 15842441
TI  - Nurses', midwives' and patients' perceptions of trained health care assistants.
AB  - AIM: This paper reports on part of a larger study and outlines Registered Nurses'
      and Midwives' perceptions of, and satisfaction with, trained health care
      assistants in a regional hospital setting in the Republic of Ireland. BACKGROUND:
      An increased reliance upon health care assistants in the clinical setting has
      highlighted the need to consider how staff and patients perceive the health care
      assistant role. FINDINGS: Nurses were satisfied with the work undertaken by
      trained health care assistants and considered that they contributed positively to
      patient care and supported nurses/midwives by undertaking non-professional
      duties. However, maternity clients reported that health care assistants were
      mostly giving direct care, and their availability was perceived to be better than
      that of qualified staff. Some nurses/midwives were reluctant to assume
      responsibility for delegation of direct care duties to health care assistants.
      CONCLUSION: The employment of health care assistants yields positive outcomes for
      staff and female clients but consideration must be given to role clarity. Further
      research into how qualified staff perceive health care assistants is important as
      such perceptions influence delegation, integration, role development and
      acceptance of health care assistants.

PMID- 15842442
TI  - Communication with critically ill patients.
AB  - AIM: This paper reports a study that investigated the experiences of a group of
      critical care Jordanian nurses concerning verbal communication with critically
      ill patients. BACKGROUND: There is evidence that communication in critical care
      settings is not sufficiently implemented in practice. Inadequate nurse-patient
      communication results in increased levels of stress and anxiety. Verbal
      communication can help patients preserve their self-identity and self-esteem,
      which in turn will enhance their well-being and optimism. METHOD: The study was
      guided by the phenomenological hermeneutics of Heidegger. Data were generated in
      2002 from in-depth interviews and overt participant observation, and analysed
      qualitatively. FINDINGS: Unconscious patients received less verbal communication
      and interaction than verbally responsive patients. CONCLUSION: Communication with
      sedated or unconscious patients in intensive care units should not be viewed as
      only an interactive process. Rather, it should be perceived as the means to give
      the information and support that such patients need.

PMID- 15842443
TI  - Processes for disciplining nurses for unprofessional conduct of a serious nature:
      a critique.
AB  - AIMS: This paper critiques the deliberative processes used by the discipline
      panels of an Australian statutory nurse regulating authority when appraising the
      alleged unprofessional conduct of nurses and determining appropriate remedies.
      BACKGROUND: Little is known about the nature and effectiveness of the
      deliberative processes used by nurse regulating authorities (NRAs) disciplinary
      panels established to appraise and make determinations in response to allegations
      of unprofessional conduct by nurses. METHODS: A qualitative exploratory
      descriptive/pragmatic research approach was used. Data were obtained from two
      case-orientated sampling units: (1) 84 Reasons for Determination made between
      1994 and 2000 and (2) a purposeful sample of 12 former and current nurse
      regulating authority members, nurse regulating authority staff and a nurse
      regulating authority representative who had experience of disciplinary
      proceedings and/or who had served on a formal hearing panel. Data were analysed
      using content and thematic analysis strategies. RESULTS: Attitudinal
      considerations (e.g. whether a nurse understood the 'wrongness' of his or her
      conduct; accepted responsibility for his or her conduct; exhibited
      contrition/shame during the hearing; was candid in his or her demeanour) emerged
      as the singularly most significant factor influencing discipline panel
      determinations. Disciplinary action is taken appropriately against nurses who
      have committed acts of deliberate malfeasance. NRAs may not, however, be dealing
      appropriately with nurses when disciplining them for making honest
      mistakes/genuine practice errors. CONCLUSION: Traditional processes used for
      appraising and disciplining nurses who have made honest mistakes in the course of
      their work need to be substantially modified as they are at odds with the models
      of human error management that are currently being advocated and adopted globally
      to improve patient safety and quality of care in health care domains.

PMID- 15842444
TI  - Palliative care for patients with cancer: district nurses' experiences.
AB  - AIM: This paper reports a study exploring district nurses' experiences of
      providing palliative care for patients with cancer and their families.
      BACKGROUND: There is an increasing demand for palliative care in the community,
      as many patients wish to die at home. District nurses are central to providing
      palliative care in the community, but there is a dearth of literature on district
      nurses' experiences in palliative care. METHOD: A Husserlian phenomenological
      approach was adopted with a purposive sample of 25 female district nurses. Data
      were collected using unstructured, tape-recorded interviews and analysed using
      Colaizzi's seven stages of data analysis. FINDINGS: Four themes were identified:
      the communication web; the family as an element of care; challenges for the
      district nurse in symptom management and the personal cost of caring.
      CONCLUSIONS: District nurses' experiences of providing palliative care to family
      units was challenging but rewarding. The emotive nature of the experience cannot
      be under-estimated, as many district nurses were touched by the varying
      situations. Whilst acknowledging the need to maintain an integrated approach to
      care, district nurses should be identified as the key workers in the complex
      situation of palliative care.

PMID- 15842445
TI  - Hardiness in families of young children with asthma.
AB  - AIMS: This paper reports a study (a) to assess whether there are cultural and
      gender differences in parents' general well-being, sense of coherence and
      perception of family hardiness when they have a young child with asthma; and (b)
      to examine the effects of parents' sense of coherence and well-being on family
      hardiness. BACKGROUND: Research on hardiness, a resilience factor that fosters
      adaptation over time, has been widely studied from an individual perspective, but
      less from the viewpoint of the family unit. In particular, no study was found
      that assessed how members of a couple interact to affect their family's
      hardiness. Consideration of this dyadic phenomenon may provide unique insight
      about how family members interact with each other faced with a challenge, such as
      the chronic illness of a child. METHODS: A cross-sectional research design was
      used with a sample of 137 two-parent families [76 from Iceland and 61 from the
      United States of America (USA)]. Questionnaires measuring sense of coherence,
      parents' well-being and family hardiness were used, and demographic data were
      also collected. RESULTS: The most striking differences in well-being were between
      mothers and fathers. In addition to a lower average on the total score for the
      well-being scale, mothers had poorer scores than fathers on the subscales of
      depression, self-control, vitality, and general health. Family hardiness differed
      between countries. The regression indicated that the individual's sense of
      coherence, depression and positive well-being (all actor effects), as well as the
      partner's anxiety (partner effect) all contributed significantly to family
      hardiness, as did nationality. CONCLUSION: Focused interventions for families
      with young children with asthma should be developed to enable them to feel more
      confident in using their resources to meet their demands and increase parents'
      general well-being and family adaptation. Research is needed to develop and test
      such interventions, particularly with diverse participant samples, encompassing
      not only a variety of ethnicities, but also a range of children's ages.

PMID- 15842446
TI  - Nurse follow-up of patients with diabetes: randomized controlled trial.
AB  - AIM: This paper reports a study comparing the outcomes of diabetic patients
      undergoing either early discharge or routine care. BACKGROUND: The hospital is
      not the best place to monitor the glycaemic control of patients with diabetes
      with no other morbidity or complications. It is an unnatural environment in which
      diet is planned and the activity level is low. The hospital is also an expensive
      place in which to treat patients. METHODS: This randomized controlled trial was
      conducted in the medical department of a regional hospital in Hong Kong. A total
      of 101 patients who needed glycaemic monitoring, but who were otherwise fit for
      discharge, were recruited. The control group continued to receive routine
      hospital care. The study group was discharged early and received a follow-up
      programme which included a weekly or biweekly telephone call from a nurse.
      FINDINGS: When compared with the control group, the study group had a greater
      decrease in HbA1c at 24 weeks, although the statistical difference was marginal
      (7.6 vs. 8.1, P = 0.06), a higher blood monitoring adherence score at both 12
      weeks (5.4 vs. 3.6, P < 0.001) and 24 weeks (5.3 vs. 3.5, P < 0.001), and a
      higher exercise adherence score at 12 weeks (5.3 vs. 3.4, P = 0.001) and 24 weeks
      (5.5 vs. 3.2, P < 0.001). The study group had a shorter hospital stay (2.2 vs.
      5.9, P < 0.001), and the net savings were HK$11,888 per patient. CONCLUSION: It
      is feasible to integrate treatment into the real life environments of patients
      with diabetes, and nurse-led transitional care is a practical and cost-effective
      model. Nurse follow-up is effective in maintaining optimal glycaemic control and
      enhancing adherence to health behaviours. Management of glycaemic control is
      better done in the community than in the hospital.

PMID- 15842447
TI  - Enhancing methodological clarity: principle-based concept analysis.
AB  - AIMS: The aim of this paper is to operationalize the principle-based method of
      concept analysis. BACKGROUND: While nursing has embraced the use of concept
      analysis as a valid and significant entree into an area of research,
      methodological development has created strategies of inquiry that vary in purpose
      and in the nature of their findings. DISCUSSION: We propose that, as the primary
      utility of concept analysis is to determine the existing state of the science so
      that further work may be strategically and appropriately planned, the method
      described as principle-based concept analysis is superior in providing evidence
      to support subsequent inquiry into the concept of interest. Three problematic
      issues are discussed in an effort to clarify and procedurally explicate the
      strategies employed in this approach: selecting disciplinary literatures for
      inclusion in the analysis; conceptually-driven sampling issues; and within- and
      across-discipline analytic techniques. CONCLUSION: In this form of concept
      analysis, each principle contributes to an understanding of the strengths and
      limitations of the present state of the concept in the scientific literature. We
      believe that this perspective will enable nursing to begin to harness the power
      of concept analysis for advancing science rather than simply imagining what a
      concept could be or constructing what we believe it should be.

PMID- 15842448
TI  - Diagnostic accuracy of the care dependency scale.
AB  - AIM: This paper reports an investigation of the diagnostic accuracy of the Care
      Dependency Scale (CDS). BACKGROUND: Assessment tools can be described in terms of
      diagnostic accuracy, or the ability to correctly classify subjects into
      clinically relevant subgroups. Diagnostic accuracy can be determined by several
      techniques as sensitivity, specificity, receiver operating curve analysis and
      likelihood ratios. METHOD: A cross-sectional design was used with data from 237
      patients from two studies. Data were collected using a questionnaire consisting
      of the CDS and the Barthel Index (BI). The CDS is a relatively new instrument and
      should be validated by comparison against an established gold standard, in this
      case the BI. Measures to quantify the validity of diagnostic tests, such as
      sensitivity, specificity, positive and negative predictive values, prevalence and
      likelihood ratios were calculated. In addition, the receiver operating
      characteristics (ROC) curve analysis was used to report the test accuracy of the
      CDS and to determine an appropriate cut-off point for care dependency detection.
      FINDINGS: The prevalence in the sample study was very high (84%). The area under
      the ROC curve for the CDS was 0.81, which indicates moderate diagnostic accuracy.
      Patients with a CDS sumscore </=68 (rule-out cut-off point) were classified as
      care dependent, all others as independent. The determination of the appropriate
      cut-off point was based on sensitivity (0.85) and positive predictive valued
      (0.90). CONCLUSION: The CDS may be used for to estimate care dependency among
      hospital patients with various conditions.

PMID- 15842449
TI  - Measuring postpartum stress.
AB  - AIMS: This paper reports a study whose purpose was to revalidate the Hung
      Postpartum Stress Scale by expanding and revising its contexts to reflect the
      social changes that have occurred in Taiwan over the last two decades.
      BACKGROUND: Existing measures of general stress, which have also been used to
      assess postpartum stress, fail to measure women's specific childbearing stressors
      during the postpartum period. The Hung Postpartum Stress Scale was initially
      developed 11 years ago by Hung and associates to measure stress in the early
      postpartum period as it occurred in the Taiwanese social milieu of the time.
      However, revalidation was needed because of rapid changes in the Taiwanese social
      system. METHODS: Employing a non-experimental, quantitative research design and a
      proportional stratified quota sampling of hospitals by birth rate, the revised
      instrument was completed by 861 postpartum women selected from clinics and
      hospitals in Taiwan. RESULTS: An exploratory common factor analysis indicated the
      structure validity of three dimensions of postpartum stress: concerns about
      maternity role attainment, concerns about negative body changes, and concerns
      about lack of social support. With regard to generalizability of the factors
      across delivery type, education level, and income status subgroups within the
      population, high coefficients of congruence were shown. Moreover, the internal
      consistency reliabilities for the total Hung Postpartum Stress Scale and its
      three dimensions across the full sample and within pertinent sub-samples showed
      that it is a reliable tool for measuring postpartum stress. CONCLUSIONS: A series
      of analyses supported the validity and reliability of the revised Hung Postpartum
      Stress Scale. Additional research is recommended using confirmatory factor
      analysis to determine the stability of the factor structure identified in the
      present study.

PMID- 15842450
TI  - Developing assessment of emergency nurse practitioner competence--a pilot study.
AB  - AIM: This paper reports a study evaluating baseline competence levels among
      Emergency Nurse Practitioners using an Objective Structured Clinical Examination.
      The study also aimed to document change in competence over time and following an
      educational intervention. BACKGROUND: Emergency Nurse Practitioners form an
      increasingly established part of the minor injury service workforce in the United
      Kingdom (UK). At present, there is no national requirement for them to undergo
      formal preparation, gain a formal qualification, have continuing professional
      development or revalidate. Given that it is certain that the use of these
      professionals to deliver unplanned emergency care will increase in the UK, skill
      maintenance and extension of skills need to be considered in order to ensure the
      continued delivery of a quality service. Objective Structured Clinical
      Examinations aim to test a wide range of knowledge and skills in an objective
      fashion and can be developed to serve a number of educational requirements.
      METHODS: A competence assessment was planned using an Objective Structured
      Clinical Examination. It was developed following questionnaire consultation with
      Emergency Nurse Practitioners and also in conjunction with Emergency Department
      specialists and experts in medical education. The Objective Structured Clinical
      Examination was piloted with Emergency Department junior doctors. Baseline
      Objective Structured Clinical Examination assessment was conducted in 2001. An
      educational intervention followed and then a further Objective Structured
      Clinical Examination assessment took place in 2002. RESULTS: A total of 17 of 20
      Emergency Nurse Practitioners consented to involvement in the study. Comparison
      of their performance showed a statistically significant overall improvement in
      performance between the two assessment periods (P < 0.05). Participant feedback
      on the experience of undertaking an Objective Structured Clinical Examination
      assessment was very positive. CONCLUSIONS: The assessment process worked well,
      and provides a framework for competence assessment that can be compared over
      time, between practitioners and between departments.

PMID- 15842451
TI  - Effects of rotating night shifts: literature review.
AB  - AIM: This paper reports a review examining the concept of sleep and its
      antithesis of fatigue, and considers the evidence on nurses' ability to cope with
      the demands of continually changing hours of work, their safety, and the impact
      any manifestations of sleep disruption may have on the care of their patients.
      While many aspects of this paper may apply to nursing in general, special
      consideration is given to nurses in the critical care environment. BACKGROUND:
      Night duty rotations are common practice in nursing, and particularly in
      specialist units. It is essential that nurses working in these environments are
      able to maintain careful and astute observation of their vulnerable patients, and
      concern arises when they may be unable to do so. Research suggests that fatigue
      can negatively affect nurses' health, quality of performance, safety and thus
      patient care, and that the effects of fatigue may be exacerbated for nurses over
      40 years of age. METHOD: The literature was examined for the 10-year period up to
      December 2003. The databases searched were Ovid, Proquest, Blackwell Science,
      EBSCO Online, Australian Health Review and WebSPIRS, using the keywords of,
      shiftwork, rosters, intensive care, fatigue, sleep deprivation and sleep studies.
      FINDINGS: There is consensus amongst researchers on the adverse psychological and
      physiological effects of night rotations on nurses when compared with their
      permanent night duty peers, particularly for those over 40 years of age. Evidence
      also suggests that the effects of fatigue on nurse performance may negatively
      affect the quality of patient care. CONCLUSIONS: The literature reinforces
      concerns about the adverse relationship between fatigue and performance in the
      workplace. Optimal standards for patient care may be difficult to achieve for
      more mature nurses, who may suffer from sleep deprivation and health problems
      associated with rotational night work and disrupted physiological rhythms.

PMID- 15842452
TI  - Professional doctorates for nurses: mapping provision and perceptions.
AB  - AIM: This paper reports a study to map the range of developments of professional
      doctorates in the United Kingdom (UK) and report the views of key stakeholders as
      to the value of the professional doctorate relative to the more traditional PhD.
      BACKGROUND: As the highest university degree that can be awarded, the traditional
      Doctor of Philosophy (PhD) represents the pinnacle of advanced learning and
      scholarly enquiry, demonstrated by subject expertise and the creation of new
      knowledge. The last decade the UK has witnessed the introduction of an
      alternative form of doctoral preparation for nurses and other health care
      professions known as the taught or professional doctorate, a form of doctoral
      provision not unlike the United States of America (USA) model of PhD in Nursing.
      METHODS: An illuminative evaluation was carried out in date in the UK in 2003.
      Data were collected using content analysis of curricula and related
      documentation, and telephone interviews with 55 academics at 41 institutions of
      higher education. RESULTS: Mapping of the professional doctorate revealed a
      continuum of provision from highly prescriptive to minimally prescriptive
      programmes and a wide range of attitudes towards the professional doctorate,
      varying from enthusiasm through ambivalence to scepticism. CONCLUSION: Educators
      face an uphill battle in convincing practitioners of the efficacy and value of
      continuing professional education at doctoral level, a challenge that is likely
      to be increased by the general lack of clarity and consensus amongst academics
      reported in this study. Shared understanding of the concept of a professional
      doctorate is needed if the benefits of these programmes are to be realised.

PMID- 15842455
TI  - Editorial. Surviving cancer.

PMID- 15842457
TI  - The impact of weekly dosing of epoetin alfa on the haematological parameters and
      on the quality of life of anaemic cancer patients.
AB  - The aim of this study was to evaluate the effectiveness and the impact of once
      weekly administration of epoetin alfa (Ea) on the management of anaemia and on
      the quality of life (QOL) of cancer patients receiving chemotherapy. Eighty
      cancer patients with life expectancy > or = 24 weeks and haemoglobin (Hb) levels
      < 10.5 g/dL were studied. After an initial screening of patients' demographic and
      clinical characteristics, Ea 40000 U once a week was administered over a period
      of 4 months. In case of patients with Hb level exceeding > 14 g/dL or in case of
      non-response, the dosage was reconsidered. Every month, data regarding Hb levels,
      clinical variations, changes in the chemotherapy regimen and transfusion use
      since the last study visit, were evaluated. The Linear Analogue Scale Assessment
      scale was used for the evaluation of the QOL. The readmissions to hospital rates
      (P < 0.002) and the transfusion use rates (P < 0.003) were significantly
      decreased comparatively with baseline. A mean increase from baseline to the final
      Hb level (P < 0.001) was established, as well as a significant improvement in the
      functional ability, energy and in the overall QOL (P < 0.001). In conclusion, the
      treatment of cancer patients with Ea once-weekly is effective and safe, improving
      their haematological parameters and QOL.

PMID- 15842458
TI  - Information and support needs of callers to the Cancer Helpline, the Cancer
      Council Victoria.
AB  - The broad aims of the present evaluation were, firstly, to describe the
      information and support needs of callers to a Cancer Helpline and, secondly, to
      describe the response of the service to these needs. A further aim was to use
      these results to develop strategies to improve the service. Anonymous caller
      information collected over a 6-year period was analysed. The setting of the study
      was the Cancer Helpline service operated by the Cancer Council Victoria within
      the state of Victoria, Australia. The caller profile was similar to that
      described in the literature, with the majority of callers being women, younger
      than the general cancer population and enquiring most commonly about breast
      cancer. Patients and their relatives called to obtain information about cancer
      diagnosis, treatment and management and to obtain psychological and emotional
      support. Callers received emotional support, were supplied with verbal and
      written information and were referred to a variety of support services. Some
      population groups are underrepresented in the data. Changes to the Helpline and
      other services over the 6-year period are described. The pattern of callers to
      the Cancer Helpline appears similar to that described in the USA and Europe. Many
      issues and challenges are common. The paper discusses additional strategies for
      meeting the information and support needs of those affected by cancer and
      describes current and suggested research areas.

PMID- 15842459
TI  - Eliciting relative preferences for two methods of colorectal cancer screening.
AB  - Two methods of mass population screening for colorectal cancer - faecal occult
      blood testing and sigmoidoscopy - have been the subject of randomized controlled
      trials in the UK. A national screening programme is currently under consideration
      and the choice of screening method remains open. To be successful, a programme
      will require high levels of uptake, and uptake is likely to depend upon subjects'
      attitudes towards the screening method introduced. Although a preferred screening
      method has already been identified from a questionnaire survey, we undertook a
      further interview study (n = 106), with a view to comparing the results of two
      different approaches to eliciting public preferences. In comparison with the
      questionnaire study, a higher proportion of interview subjects stated a
      preference. Interview subjects were generally more favourably disposed towards
      sigmoidoscopy, excepting those with previous experience. Compared with the
      questionnaire survey, the interviews provided richer information on the reasons
      for preferences offered. Individual preferences were evidently subjective and
      dependant on attitudes towards a variety of method characteristics, such as
      discomfort, convenience and perceived sophistication. Characteristics such as age
      and low income, which had predicted preferences in the questionnaire study,
      predicted preferences in the interview study also. The difference between the
      results obtained by the different elicitation techniques can be explained in
      terms of the differential provision of information and sample selection.
      Conclusions made about public preferences are likely to depend on the technique
      employed in eliciting them.

PMID- 15842460
TI  - When a child cannot be cured - reflections of health professionals.
AB  - This article reports on a study exploring the challenges and complexities of
      caring for a child with cancer no longer responding to curative therapy. The
      difficulties that health professionals face when initiating and providing
      palliative care to children with cancer is largely unexplored. A greater
      understanding of these challenges is needed to inform the development of
      effective models of care. Participatory group discussions and in-depth interviews
      were used to explore how health professionals from three disciplines - nursing,
      medicine and social work - view their role during the shift from cure to
      palliation. Interviews were tape-recorded and transcribed verbatim. Content and
      thematic analysis was used to identify themes and important messages in the
      transcripts. This study illustrates how the trajectory of childhood cancer is
      characterized by uncertainty, especially following relapse where there is reduced
      clarity surrounding the child's outcome. Prognostic uncertainty and continued
      hope for survival make the shift to palliation difficult, raising questions about
      the applicability of traditional palliative care models for these children and
      their families. Decision making in this context is complicated by a lack of
      clarity, uncertainty and continued hope. Shifting the focus of care from cure to
      palliation is not experienced as a discrete event but rather, as an awareness and
      acceptance that slowly develops. New models of care that incorporate palliative
      care throughout the disease trajectory are recommended.

PMID- 15842461
TI  - Determining patient preferences for improved chemotoxicity during treatment for
      advanced bladder cancer.
AB  - Determining patient preferences for improved chemotoxicity during treatment for
      advanced bladder cancer Conventional treatment for advanced bladder cancer is
      methotrexate, vinblastine, doxorubicin plus cisplatin (MVAC), with a median
      survival of 1 year but significant toxicity. The newer combination of gemcitabine
      plus cisplatin (GC) has demonstrated comparable survival and an improved toxicity
      profile (Von der Maase et al. 2000). At present, the importance to patients of
      the toxicity of chemotherapy has not been widely studied. An earlier study in
      bladder cancer indicated that toxicity was an important determinant of treatment
      preference (Davey et al. 2000). A study of preferences for advanced bladder
      cancer therapy in the UK was proposed.

PMID- 15842462
TI  - Use of complementary and alternative medicine by Brazilian oncologists.
AB  - Complementary and alternative medicine (CAM) is frequently employed by patients
      with cancer. An extensive survey was conducted among Brazilian cancer physicians
      to understand their attitude towards CAM. A questionnaire was sent to all 655
      members of the Brazilian Cancer Society asking what is their opinion regarding
      CAM and if they would prescribe any CAM modality for their patients. They were
      also questioned regarding their degree of awareness of CAM self-administration by
      their patients. Overall, 119 questionnaires were returned to us (18%). Most
      oncologists knew at least one type of CAM (96.6%) and 76.7% had previously made
      use of at least one type of CAM for themselves. We observed that 76 (63.8%) of
      the oncologists used to ask their patients about CAM utilization and 37.8%
      described at least one reason to stimulate its use (68.8% as complementary
      treatment). Only 10% of the oncologists would prescribe at least one type of CAM
      and this attitude correlated significantly with previous physicians' use of CAM
      and with being a clinical oncologist as well as with having questioned patients
      about CAM use. Most oncologists (80.7%) would not indicate the use of CAM, mainly
      for lack of scientific proof of its efficacy (56.2%). Physicians knew many kinds
      of CAM and had frequently used some of them themselves, but only a minority of
      Brazilian oncologists would indicate them. As CAM use is very prevalent in our
      population, we believe that most of its utilization depends, probably, on
      patient's own and independent initiatives. However, these results should be
      viewed with caution because of the low response rate we observed in this study.

PMID- 15842463
TI  - Attitudes towards cancer among elderly Bangladeshis in London: a qualitative
      study.

PMID- 15842464
TI  - Randomized crossover trial of intravenous 5-FU versus oral UFT both modulated by
      leucovorin: a one-centre experience.
AB  - Although intravenous (IV) 5-fluorouracil (5-FU) and uracil/futraful (UFT) have
      comparable antitumour efficacy in the treatment of metastatic colorectal cancer
      (MCC), we wanted to assess which of these two regimens would be preferred by our
      patients. We randomized 20 previously untreated patients with MCC at our centre
      to receive oral UFT or bolus IV 5-FU both associated with leucovorin. After the
      first cycle patients were crossed over to the other arm. Before the third cycle
      we left patients to choose one of the regimens to continue their treatment until
      disease progression. Two patients chose 5-FU and 18 chose UFT (P < 0.001). Fewer
      side effects (50%) and convenience of home treatment (40%) were the main reasons
      for their choice for the oral regimen. UFT induced less mucositis (P = 0. 02) and
      diarrhoea (P = 0. 01). We conclude that convenience and lower toxicity may
      explain the observed preference for oral UFT.

PMID- 15842465
TI  - Patients with haematological malignancies show a restricted body image focusing
      on function and emotion.
AB  - The diagnosis of cancer threatens the psychological and bodily integrity. Based
      on this assumption, we aimed to explore how newly diagnosed patients cope with
      special regard to the body image (BI). In total, 40 patients (32 haematological
      malignancies) were assessed by questionnaires on mood, complaints, self
      regulation and quality of life (QOL). The BI was assessed by the 'Body Grid'
      which reveals the constructs patients choose to characterize the body. The
      constructs were categorized using a model of six predefined categories
      comprising: emotion, control, activity, strength, function and appearance.
      Tinnitus sufferers and medical students served as comparison groups. Cancer
      patients showed significantly more anxious depression and a significantly lower
      QOL than controls. Their BI was restricted, focusing the functional status of
      body organs (e.g. opposing healthy vs. ill organs) as well as emotional aspects
      (e.g. trust vs. fear). The data convey fundamental psychological distress in
      newly diagnosed cancer patients. Restriction of BI and use of functional
      constructs may help to buffer the threat to body integrity. The emotional
      constructs reflect the existential impact. The data give a clear indication for
      the need for early psychosocial support which should aim at stabilizing the
      psychological and bodily integrity of the patient.

PMID- 15842466
TI  - Differences in attitudes between patients with primary colorectal cancer and
      patients with secondary colorectal cancer: is it reflected in their willingness
      to participate in drug trials?
AB  - Recruitment of patients into drug trials is essential in order to evaluate new
      treatments. Knowing why patients enter drug trials and their fears regarding them
      can be used in future research to ensure good recruitment and provide a
      supportive atmosphere for patients. Forty patients with colorectal cancer and 30
      patients with colorectal liver metastases were asked to participate in a drug
      trial involving the oral consumption of a diet-derived agent of unknown
      therapeutic action. All patients agreeing or refusing to participate were asked
      to complete a short questionnaire with a series of options detailing the reasons
      behind their decision. Patients with colorectal hepatic metastases were motivated
      by altruism in entering the trial (e.g. helping others, helping the investigator)
      and displayed a realistic expectation that the drug would give little direct
      benefit to them. Patients with primary colorectal tumours were motivated by more
      'selfish' reasons such as helping themselves and displayed an unrealistic
      expectation concerning any therapeutic benefit from the trial drug. Over 90% of
      all patients polled stated that their decision was made after reading the patient
      information leaflet. Patients with different stages of the same disease have very
      different fears and anticipations of drug trials, which need to be addressed
      specifically. The importance of the initial contact is demonstrated. Unrealistic
      expectations regarding the trial drug are common despite clear information to the
      contrary.

PMID- 15842467
TI  - Portrayals of treatment decision-making on popular breast and prostate cancer web
      sites.
AB  - The objective of this study was to describe the messages about treatment decision
      making on popular cancer web sites, with particular reference to gender
      differences. The two most popular UK based web sites for breast and prostate
      cancer were chosen. Qualitative and quantitative comparative content analysis of
      the two case study web sites were performed. Web site portrayals of treatment
      decision-making by men with prostate cancer emphasize the obligation to be
      decisive, using information derived from medical sources, with minimal
      consultation with families and friends. Portrayals of treatment decision-making
      by women with breast cancer emphasize their family obligations, their need to
      make decisions about matters other than treatment, their right to opt out of
      decision-making, to take time, sometimes change their minds, consult with
      families and friends, and thereby take non-medical factors into account. This
      study will help health care practitioners understand the different factors that
      men and women feel obliged to consider when making decisions about their cancer
      treatments, and the role of the Internet in reinforcing gender differences.

PMID- 15842468
TI  - Patterns and barriers in information disclosure between health care professionals
      and relatives with cancer patients in Greek society.
AB  - The issue of whether, how and how much to tell cancer patients concerning
      diagnosis is still approached in various ways across different countries and
      cultures. The health care team-patient relationship is a triangle consisting of
      the health care professionals, the patient and the family. Each part supports the
      other two and is affected by the changes that happen in the triangle. The
      objective of the study was to investigate the communication context through which
      health care professionals and families with cancer patients interact. In Greece,
      physicians have the tendency to tell the truth more often today than in the past,
      although the majority still disclose the truth to the next of kin. Nurses in
      Greece are considered to be the most suitable health care professionals for the
      patients to share their thoughts and feelings with. Nevertheless, the decision on
      information disclosure lies with the treating physician. In Greek society the
      patient's family plays an important role in the provision of care and information
      disclosure. They often decide on the patient's behalf.

PMID- 15842469
TI  - Use of a Port-a-Cath system in the home setting for the treatment of symptomatic
      recurrent malignant pleural effusion.
AB  - Symptomatic malignant pleural effusions represent a common problem in metastatic
      cancers and are associated with a significant morbidity. Pleurodesis still
      remains the primary therapy of choice. In a few cases, however, pleurodesis is
      unsuccessful because of a limited lung expansion and pleuroperitoneal shunts have
      been used. We describe two cases where an implantable PORT-A-CATH system is used
      for regular drainage of the pleural effusion. The main advantage of this
      technique is the fact that the procedure of drainage can be performed by a nurse
      in the home setting.

PMID- 15842470
TI  - Simultaneous bilateral trochanteric fractures during squatting in a patient with
      multiple myeloma.
AB  - Pathologic bone fractures are usually confined to the trunk in multiple myeloma
      (MM). But bilateral trochanteric fractures have not been reported in patients
      with MM before. Radiographic, histological and immunoelectrophoresis revealed
      typical features of MM. This report points out the importance of physical
      rehabilitation of patients in addition to chemotherapy in adaptation to the
      activities of daily living.

PMID- 15842479
TI  - The evolution of self-fertilization and inbreeding depression under pollen
      discounting and pollen limitation.
AB  - We model the evolution of plant mating systems under the joint effects of pollen
      discounting and pollen limitation, using a dynamic model of inbreeding
      depression, allowing for partial purging of recessive lethal mutations by
      selfing. Stable mixed mating systems occur for a wide range of parameter values
      with pollen discounting alone. However, when typical levels of pollen limitation
      are combined with pollen discounting, stable selfing rates are always high but
      less than 1 (0.9<s<1 in most cases); in this situation, complete selfing does not
      evolve because pollen discounting becomes very large at high selfing rates, so
      that the automatic advantage of selfing changes to a disadvantage. These results
      suggest that mixed mating systems with high selfing rates can be maintained by
      selection, whereas mixed mating systems with low to moderate selfing rates are
      more likely attributable to unavoidable geitonogamous selfing.

PMID- 15842480
TI  - The influence of mating system on the intensity of parent-offspring conflict in
      primates.
AB  - An evolutionary conflict of interest exists between parents and their offspring
      over the partitioning of parental investment (PI) among siblings. When the direct
      fitness benefits to offspring of increased PI, outweigh the inclusive fitness
      costs from lost future sibling fitness, selection should favour the evolution of
      offspring selfishness over altruism. In theory, this conflict is heightened when
      females are not strictly monogamous, as current offspring should be less
      altruistic towards future half-siblings than they would be towards full-siblings.
      Using data collected on foetal growth rate (representing prenatal PI) in
      primates, I test the prediction from theory that the resolution of the parent
      offspring conflict will be closer to the offspring's evolutionary optima in
      polyandrous species than in more monandrous species. Using phylogenetic
      comparative analysis, and controlling for allometry, I show that offspring are
      able to obtain more PI when the probability of future full-siblings decreases,
      and that this is most pronounced in taxa where there is the opportunity for
      direct foetal access to the maternal bloodstream. These results support the
      hypothesis that the resolution of prenatal PI conflict is influenced by both a
      species' mating system and by its placental structure.

PMID- 15842481
TI  - Genetic and environmental variation in the visual properties of bluefin
      killifish, Lucania goodei.
AB  - Animals use their sensory systems to detect information about the external
      environment in order to find mates, locate food and habitat and avoid predators.
      Yet, there is little understanding of the relative amounts of genetic and/or
      environmental variation in sensory system properties. In this paper, we
      demonstrate genetic and environmental variation in opsin expression in a
      population of bluefin killifish. We measured expression of five opsins (which
      correlates with relative frequency of corresponding cones) using quantitative,
      real-time polymerase chain reaction for offspring from a breeding study where
      offspring were raised under different lighting conditions. Sire (i.e. genetic)
      effects were present for opsin found in yellow photopigment. Dam effects were
      present for opsins that create violet, blue and red photopigment. Lighting
      conditions affected expression of all opsins except SWS2A and mimicked the
      pattern found among populations. These results highlight the fact that sensory
      systems are both plastic and yet readily evolvable traits.

PMID- 15842482
TI  - Hybridization and invasiveness in the freshwater snail Melanoides tuberculata:
      hybrid vigour is more important than increase in genetic variance.
AB  - Many invasive taxa are hybrids, but how hybridization boosts the invasive process
      remains poorly known. We address this question in the clonal freshwater snail
      Melanoides tuberculata from Martinique, using three parental and two hybrid
      lines. We combine an extensive field survey (1990-2003) and a quantitative
      genetic experiment to show that hybrid lines have outcompeted their parents in
      natural habitats, and that this increased invasiveness co-occurred with
      pronounced shifts in life-history traits, such as growth, fecundity and juvenile
      size. Given the little time between hybrid creation and sampling, and the
      moderate standing genetic variance for life-history traits in hybrids, we show
      that some of the observed trait changes between parents and hybrids were unlikely
      to arise only by continuous selection. We therefore suggest that a large part of
      hybrid advantage stems from immediate heterosis upon hybridization.

PMID- 15842483
TI  - Direct and indirect assortative mating: a multivariate approach to plant
      flowering schedules.
AB  - This paper develops methods to partition the phenotypic correlation between mates
      for a focal trait--the standard measure for assortative mating--into a direct
      component and additional indirect components. Indirect assortative mating occurs
      when a nonassorting trait is correlated within individuals to a directly
      assorting trait. Direct and indirect assortative mating is assessed for flowering
      phenology in Brassica rapa. The flowering time of pollen recipients (mothers) was
      strongly correlated (rho=0.67) to that of potential pollen donors (fathers).
      Similarly, recipients and donors were correlated for duration of their flowering
      periods (rho=0.32) and stem diameters (rho=0.52). A partitioning of between-mate
      correlations revealed direct assortative mating for flowering time and period
      duration. However, assortment for stem diameter is explained solely through its
      correlation to flowering time. Examination of standard quantitative genetic
      theory shows that indirect assortative mating inflates genetic variance in a
      focal trait and the genetic covariance between focal and phenotypically
      correlated traits.

PMID- 15842484
TI  - Polymorphic mimicry, microhabitat use, and sex-specific behaviour.
AB  - In order to assess the adaptive importance of microhabitat segregation for the
      maintenance of mimetic diversity, I explore how flight height varies between the
      sympatric forms of the polymorphic butterfly Heliconius numata and their
      respective models in the genus Melinaea. There is no evidence for vertical
      stratification of mimicry rings in these tiger-patterned butterflies, but males
      of H. numata tend to fly significantly higher than females and the Melinaea
      models. This difference in microhabitat preference likely results from females
      searching for host plants whereas males are patrolling for mates. I then present
      an extension of Muller's mimicry model for the case of partial behavioural or
      spatial segregation of sexes. The analysis suggests that sex-specific behaviours
      can make mimicry more beneficial, simply by reducing the effective population
      size participating in mimicry. The interaction between mimicry and sex-specific
      behaviours may therefore facilitate the evolution of polymorphism via enhanced,
      fine-scale local adaptation.

PMID- 15842485
TI  - Sperm competition and the evolution of testes size in birds.
AB  - Comparative analyses suggest that a variety of ecological and behavioural factors
      contribute to the tremendous variability in extrapair mating among birds. In an
      analysis of 1010 species of birds, we examined several ecological and behavioural
      factors in relation to testes size; an index of sperm competition and the extent
      of extrapair mating. In univariate and multivariate analyses, testes size was
      significantly larger in species that breed colonially than in species that breed
      solitarily, suggesting that higher breeding density is associated with greater
      sperm competition. After controlling for phylogenetic effects and other
      ecological variables, testes size was also larger in taxa that did not
      participate in feeding their offspring. In analyses of both the raw species data
      and phylogenetically independent contrasts, monogamous taxa had smaller testes
      than taxa with multiple social mates, and testes size tended to increase with
      clutch size, which suggests that sperm depletion may play a role in the evolution
      of testes size. Our results suggest that traditional ecological and behavioural
      variables, such as social mating system, breeding density and male parental care
      can account for a significant portion of the variation in sperm competition in
      birds.

PMID- 15842486
TI  - Natural selection and genetic variation for female resistance to harm from males.
AB  - The sexual conflict hypothesis predicts that males evolve traits that exploit the
      higher parental investment of females, which generates selection for females to
      counter-evolve resistance. In Drosophila melanogaster it is now established that
      males harm females and that there is genetic variation among males for the degree
      of this harm. Genetic variation among females for resistance to harm from males,
      and the corresponding strength of selection on this variation, however, have not
      been quantified previously. Here we carryout a genome-wide screen for female
      resistance to harm from males. We estimate that the cost of interactions with
      males depresses lifetime fecundity of females by 15% (95% CI: 8.2-22.0), that
      genetic variation for female resistance constitutes 17% of total genetic
      variation for female adult fitness, and that propensity to remate in response to
      persistent male courtship is a major factor contributing to genetic variation for
      female resistance.

PMID- 15842487
TI  - A chemical level in the coevolutionary arms race between an ant social parasite
      and its hosts.
AB  - Here we investigate the coevolutionary interactions between the slavemaking ant
      Protomognathus americanus and its Temnothorax hosts on a chemical level. We show
      that, although this social parasite is principally well-adapted to its hosts'
      cuticular hydrocarbon profile, there are pronounced differences in the fine
      tuning of this adaptation. Between populations, chemical adaptation varies with
      host community composition, as the parasite faces a trade-off when confronted
      with more than one host species. In addition to adaptation of its own chemical
      signature, the slavemaker causes a reciprocal adjustment in its slaves' cuticular
      profile, the degree of which depends on the slave species. On the host side,
      successful parasite defence requires efficient enemy recognition, and in
      behavioural aggression trials, host colonies could indeed discriminate between
      invading slaves, which commonly accompany slavemakers on raids, and free-living
      conspecifics. Furthermore, hosts shifted their acceptance threshold over the
      seasons, presumably to reduce the costs of defence.

PMID- 15842488
TI  - Macroevolutionary trends in the Dinosauria: Cope's rule.
AB  - Cope's rule is the tendency for body size to increase over time along a lineage.
      A set of 65 phylogenetically independent comparisons, between earlier and later
      genera, show that Cope's rule applied in dinosaurs: later genera were on average
      about 25% longer than the related earlier genera to which they were compared. The
      tendency for size to increase was not restricted to a particular clade within the
      group, nor to a particular time within its history. Small lineages were more
      likely to increase in size, and large lineages more likely to decrease: this
      pattern may indicate an intermediate optimum body size, but can also be explained
      as an artefact of data error. The rate of size increase estimated from the
      phylogenetic comparisons is significantly higher than the rate seen across the
      fauna as a whole. This difference could indicate that within-lineage selection
      for larger size was opposed by clade selection favouring smaller size, but data
      limitations mean that alternative explanations (which we discuss) cannot be
      excluded. We discuss ways of unlocking the full potential usefulness of
      phylogenies for studying the dynamics of evolutionary trends.

PMID- 15842489
TI  - Habitat specialization and adaptive phenotypic divergence of anuran populations.
AB  - We tested for adaptive population structure in the frog Rana temporaria by
      rearing tadpoles from 23 populations in a common garden experiment, with and
      without larval dragonfly predators. The goal was to compare tadpole phenotypes
      with the habitats of their source ponds. The choice of traits and habitat
      variables was guided by prior information about phenotypic function. There were
      large differences among populations in life history, behaviour, morphological
      shape, and the predator-induced plasticities in most of these. Body size and
      behaviour were correlated with predation risk in the source pond, in agreement
      with adaptive population divergence. Tadpoles from large sunny ponds were
      morphologically distinct from those inhabiting small woodland ponds, although
      here an adaptive explanation was unclear. There was no evidence that plasticity
      evolves in populations exposed to more variable environments. Much among
      population variation in phenotype and plasticity was not associated with habitat,
      perhaps reflecting rapid changes in wetland habitats.

PMID- 15842490
TI  - Lower fecundity in parthenogenetic geckos than sexual relatives in the Australian
      arid zone.
AB  - Theoretical models of the advantage of sexual reproduction typically assume that
      reproductive output is equal in sexual and parthenogenetic females. We tested
      this assumption by comparing fecundity between parthenogenetic and sexual races
      of gekkonid lizards in the Heteronotia binoei complex, collected across a 1200 km
      latitudinal gradient through the Australian arid zone. Under laboratory
      conditions, parthenogenetic geckos had approximately 30% lower fecundity when
      compared with their sexual progenitors, irrespective of body size. Reflecting
      clutch-size constraints in gekkonids, this fecundity difference was mainly
      because of fewer clutches over a shorter period. When parthenogens were compared
      more broadly with all coexisting sexual races across the latitudinal gradient,
      parthenogens had lower fecundity than sexuals only when corrected for body size.
      Differences in fecundity between parthenogens and coexisting sexual races
      depended on which sexual race was considered. There was no significant
      relationship between fecundity and parasite (mite) load, despite significantly
      higher mite loads in parthenogens than in sexual races.

PMID- 15842491
TI  - Contemporary gene flow and the spatio-temporal genetic structure of subdivided
      newt populations (Triturus cristatus, T. marmoratus).
AB  - Gene flow and drift shape the distribution of neutral genetic diversity in
      metapopulations, but their local rates are difficult to quantify. To identify
      gene flow between demes as distinct from individual migration, we present a
      modified Bayesian method to genetically test for descendants between an immigrant
      and a resident in a nonmigratory life stage. Applied to a metapopulation of pond
      breeding European newts (Triturus cristatus, T. marmoratus) in western France,
      the evidence for gene flow was usually asymmetric and, for demes of known census
      size (N), translated into maximally seven reproducing immigrants. Temporal
      sampling also enabled the joint estimation of the effective demic population size
      (Ne) and the immigration rate m (including nonreproductive individuals). Ne
      ranged between 4.1 and 19.3 individuals, Ne/N ranged between 0.05 and 0.65 and
      always decreased with N; m was estimated as 0.19-0.63, and was possibly biased
      upwards. We discuss how genotypic data can reveal fine-scale demographic
      processes with important microevolutionary implications.

PMID- 15842492
TI  - Competing dwarf males: sexual selection in an orb-weaving spider.
AB  - Hypotheses for the adaptive significance of extreme female-biased sexual size
      dimorphism (SSD) generally assume that in dimorphic species males rarely
      interfere with each other. Here we provide the first multivariate examination of
      sexual selection because of male-male competition over access to females in a
      species with 'dwarf' males, the orb-weaving spider Argiope aurantia. Male A.
      aurantia typically try to mate opportunistically during the female's final moult
      when she is defenceless. We show that, contrary to previous hypotheses, the local
      operational sex ratio (males per female on the web) is male-biased most of the
      season. Both interference and scramble competition occur during opportunistic
      mating, the former leading to significant selection for large male body size.
      Male condition and leg length had no effect on mating success independent of
      size. We discuss these findings in the context of the evolution of extreme female
      biased SSD in this clade.

PMID- 15842493
TI  - Direct and correlated responses to artificial selection on male mating frequency
      in the stalk-eyed fly Cyrtodiopsis dalmanni.
AB  - Traditionally it was thought that fitness-related traits such as male mating
      frequency, with a history of strong directional selection, should have little
      additive genetic variance and thus respond asymmetrically to bidirectional
      artificial selection. However, recent findings and theory suggest that a balance
      between selection for increased male mating frequency and opposing selection
      pressures on physiologically linked traits will cause male mating frequency to
      have high additive genetic variation and hence respond symmetrically to
      selection. We tested these hypotheses in the stalk-eyed fly, Cyrtodiopsis
      dalmanni, in which males hold harems comprising many females and so have the
      opportunity to mate at extremely high frequencies. We subjected male stalk-eyed
      flies to artificial selection for increased ('high') and decreased ('low') mating
      frequency in the presence of ecologically realistic, high numbers of females.
      High line males mated significantly more often than control or low line males.
      The direct response to selection was approximately symmetric in the high and low
      lines, revealing high additive genetic variation for, and no significant genetic
      constraints on, increased male mating frequency in C. dalmanni. In order to
      investigate trade-offs that might constrain male mating frequency under natural
      conditions we examined correlated responses to artificial selection. We measured
      accessory gland length, testis length and eyespan after 7 and 14 generations of
      selection. High line males had significantly larger accessory glands than low
      line males. No consistent correlated responses to selection were found in testis
      length or eyespan. Our results suggest that costs associated with the production
      and maintenance of large accessory glands, although yet to be identified, are
      likely to be a major constraint on mating frequency in natural populations of C.
      dalmanni.

PMID- 15842494
TI  - Adaptive evolution in GroEL from distantly related endosymbiotic bacteria of
      insects.
AB  - Many symbioses between bacteria and insects resulted from ancient infections
      followed by strict vertical transmission within host lineages. The strong
      bottlenecks under which this transmission occurs promote the neutral fixation of
      slightly deleterious mutations by genetic drift. As predicted by Muller's
      ratchet, this fixation will drive endosymbiotic bacteria through an irreversible
      dynamics of fitness loss. The chaperonin GroEL has been proposed as a
      compensatory mechanism whereby endosymbiotic bacteria of aphids persist. Here, we
      show that endosymbiotic bacteria of insects from two phylogenetically very
      distant bacterial phyla have fixed amino acid substitutions by positive selection
      in functionally important GroEL regions involved in either GroES/peptide binding
      or in the en bloc movement of the GroEL apical domain. These results, together
      with the high levels of constitutive expression of GroEL in these endosymbionts,
      provide valuable insights into the evolution of a molecular mechanism responsible
      for the maintenance of the symbiotic lifestyle.

PMID- 15842495
TI  - Within clutch co-variation of egg mass and sex in the black-headed gull.
AB  - Female birds of several species have control over the production of daughters and
      sons. However, most studies failed to find a relationship between egg size and
      sex. This is intriguing as adjustment of egg size would constitute a powerful
      tool for the female to meet different resource demands of the sexes, particularly
      in size dimorphic species. Our results show that, within clutches of black-headed
      gulls (Larus ridibundus) the proportion of males was positively associated with
      egg mass. This applied for all three laying positions, independently of the
      absolute egg mass. There was a significant relationship between the distribution
      of the sexes over the laying sequence and the egg mass change. When egg mass
      decreased over the sequence, first-laid eggs were male biased and last-laid eggs
      female biased, and vice versa. The potential adaptive value of this allocation
      strategy is evaluated with regard to male sensitivity to egg quality and
      competitive differences between the sexes.

PMID- 15842496
TI  - Evolution of bite force in Darwin's finches: a key role for head width.
AB  - Studies of Darwin's finches of the Galapagos Islands have provided pivotal
      insights into the interplay of ecological variation, natural selection, and
      morphological evolution. Here we document, across nine Darwin's finch species,
      correlations between morphological variation and bite force capacity. We find
      that bite force correlates strongly with beak depth and width but only weakly or
      not at all with beak length, a result that is consistent with prior
      demonstrations of natural selection on finch beak morphology. We also find that
      bite force is predicted even more strongly by head width, which exceeds all beak
      dimensions in predictive strength. To explain this result we suggest that head
      width determines the maximum size, and thus maximum force generation capacity of
      finch jaw adductor muscles. We suggest that head width is functionally relevant
      and may be a previously unrecognized locus of natural selection in these birds,
      because of its close relationship to bite force capacity.

PMID- 15842497
TI  - Hamilton's rule, imprinting and parent-offspring conflict over seed mass in
      partially selfing plants.
AB  - When genes in the offspring control the provisioning of the seed, the optimal
      seed size can be calculated exactly by applying Hamilton's rule. When seed size
      is a compromise between mother and offspring, we predict that outcrossing plant
      species produce larger seeds than selfers. This trend was found in the British
      flora and in a number of well-studied plant families. The analysis was extended
      to imprinting, a conditional strategy in which a gene in the offspring takes more
      resources when derived from the father than from the mother. The conditions for
      imprinting to be selected were rather restrictive. The analysis is relevant for
      the current debate about the evolution of imprinting in Arabidopsis thaliana.

PMID- 15842498
TI  - Morphological divergence and origin of sympatric populations of European
      whitefish (Coregonus lavaretus L.) in Lake Femund, Norway.
AB  - Combining morphological and genetic analysis, we compared patterns of
      diversification within and between morphs among sympatric European whitefish
      (Coregonus lavaretus L.) populations in Lake Femund, Norway. Seven external
      populations, from potential colonization routes into Lake Femund were included.
      We found that deep-, shallow-, river- and bay spawning populations are distinct
      morphs in Lake Femund. Within morphs, populations range from being similar
      genetically (Fst=0-0.005) among deep-spawning populations to being highly
      differentiated (Fst=0.153) between bay-spawning populations. Between morphs,
      genetic differences ranged from a low (Fst=0.008-0.022) between deep- and shallow
      spawning populations to high difference (Fst=0.125-0.143) between shallow- and
      bay-spawning populations. A higher proportion of molecular variance was seen
      among (3.9%) than within morphs (2.8%). The adaptive gene combinations behind the
      four morphs seem to have originated within the lake, although the lake could have
      been colonized from more than one source population.

PMID- 15842499
TI  - Inheritance of song and stridulatory peg number divergence between Chorthippus
      brunneus and C. jacobsi, two naturally hybridizing grasshopper species
      (Orthoptera: Acrididae).
AB  - Knowledge of the genetic basis of divergence in mating signal characters that
      contribute to reproductive isolation is critical to understanding speciation.
      Here, we describe a semi-automated system for characterizing grasshopper acoustic
      signals. We used this system to study the genetic basis of divergence in three
      male calling song components [echeme (EL), syllable (SL) and phrase (PL) lengths]
      between Chorthippus brunneus and C. jacobsi, two species of grasshoppers that
      hybridize in northern Spain. We also studied the number of pegs in the
      stridulatory file. For all characters, additive effects accounted for most of the
      genetic differentiation between species. However, the three song components also
      showed small but significant epistatic effects. No sex linkage was detected.
      Wright-Castle-Lande estimates of the minimum numbers of genetic factors
      underlying song and peg number divergence were low: peg number (n(e)=5.87+/
      5.84), SL (n(e)=2.37+/-4.79) and PL (n(e)=0.87+/-0.86). On the other hand, EL
      appeared to be controlled by many genes. These results suggest that divergence in
      SL and PL might be driven by sexual selection whereas EL might not be under
      selection. This is consistent with experimental results on female song preference
      in related species. However, the fact that few factors appear to underlie the
      differences in peg number is surprising. Peg number is not closely related to
      song characteristics. It often varies between closely related grasshopper species
      and it has been assumed to be a neutral character. The biometrical approaches
      used here tend to underestimate the number of factors influencing a trait but
      provide valuable background for subsequent quantitative trait loci analyses.

PMID- 15842500
TI  - Locally differentiated cryptic pigmentation in the freshwater isopod Asellus
      aquaticus.
AB  - A repeated pattern of background colour matching in animals is an indication that
      pigmentation may be cryptic. Here, we examine the relationship between
      pigmentation of the freshwater isopod Asellus aquaticus and background darkness
      in 29 lakes, wetlands and ponds in Southern Sweden. The results show that Asellus
      pigmentation was correlated with substrate darkness across all localities. In
      seven localities, in which two contrasting substrate types were noted, Asellus
      populations were differentiated with respect to pigmentation. These findings thus
      provide phenomenological support for cryptic pigmentation in Asellus.
      Pigmentation generally increased with body size, but the relationship between
      pigmentation and size differed among localities, possibly as a result of
      differences in correlational selection on pigmentation and size. Selection thus
      appears to have resulted in local differentiation over a small spatial scale,
      even within lakes and wetlands. This differentiation is a likely cause behind
      elevated phenotype variation noted in localities with two substrate types,
      suggesting that habitat heterogeneity promotes genetic diversity.

PMID- 15842501
TI  - Experimental sexual selection in Chlamydomonas.
AB  - Sexual and asexual lines of the unicellular chlorophyte Chlamydomonas reinhardtii
      were propagated for about 100 sexual cycles and 1000 vegetative cycles in
      contrasted environments, liquid and solid growth media, in order to generate
      divergent natural and sexual selection. Sexual lines were transferred by many
      zygotes or by a single zygote in each sexual generation. By the end of the
      experiment zygote production was in the order sexual mass-transfer>sexual single
      zygote>asexual>ancestor. The direct response to sexual selection was large, with
      zygote production increasing by about two orders of magnitude, mainly because
      mating had become spontaneous instead of being invoked by nitrogen starvation.
      Asexual lines became sexually sterilized by the fixation of a single mating type.
      Sexual selection caused a radical shift in the gender system, with homothallism
      spreading to high frequency in all sexual lines of this normally heterothallic
      species. This may have been caused by the transposition of a mating-type gene to
      an autosome. No substantial degree of environment-specific mating evolved,
      however, and thus no sexual isolation indicative of incipient speciation. It is
      possible that selection experiments of this kind are unlikely to induce sexual
      isolation because mating-type genes evolve in a saltatory fashion.

PMID- 15842502
TI  - The benefits of polyandry in the free-spawning polychaete Galeolaria caespitosa.
AB  - In many species, females are thought to benefit from polyandry due to the reduced
      risks of fertilization by genetically incompatible sperm. However, few studies
      that have reported such benefits have directly attributed variation in female
      reproductive success to the interacting effects of males and females at
      fertilization. In this paper, we determine whether male x female interactions
      influence fertilization in vitro in the free-spawning, sessile polychaete
      Galeolaria caespitosa. Furthermore, we determined whether polyandry results in
      direct fertilization benefits for females by experimentally manipulating the
      number of males contributing towards staged spawning events. To test for male x
      female interaction effects we performed an initial experiment that crossed seven
      males with six females (in all 42 combinations), enabling us to assess
      fertilization rates for each specific male-female pairing and attribute variation
      in fertilization success to males, females and their interaction. This initial
      experiment revealed a strong interaction between males and females at
      fertilization, confirming that certain male-female combinations were more
      compatible than others. A second experiment tested the hypothesis that polyandry
      enhances female reproductive success by exposing each female's eggs to either a
      single male's sperm (monandry) or the sperm from three males simultaneously
      (polyandry). We performed this second experiment at two ecologically relevant
      sperm concentrations. This latter experiment revealed a strong fertilization
      benefit of polyandry, independent of the effects of sperm concentration (which
      were also significant). We suggest that these direct fertilization gains arising
      from polyandry will constitute an important source of selection on females to
      mate multiply in nature.

PMID- 15842504
TI  - Cerebral metabolic alterations in children with diabetic ketoacidosis.

PMID- 15842505
TI  - Genetics of Type 2 diabetes.
AB  - Type 2 diabetes (T2D) has become a health-care problem worldwide, with the rise
      in disease prevalence being all the more worrying as it not only affects the
      developed world but also developing nations with fewer resources to cope with yet
      another major disease burden. Furthermore, the problem is no longer restricted to
      the ageing population, as young adults and children are also being diagnosed with
      T2D. In recent years, there has been a surge in the number of genetic studies of
      T2D in attempts to identify some of the underlying risk factors. In this review,
      I highlight the main genes known to cause uncommon monogenic forms of diabetes
      (e.g. maturity-onset diabetes of the young--MODY--and insulin resistance
      syndromes), as well as describe some of the main approaches used to identify
      genes involved in the more common forms of T2D that result from the interaction
      between environmental risk factors and predisposing genotypes. Linkage and
      candidate gene studies have been highly successful in the identification of genes
      that cause the monogenic variants of diabetes and, although progress in the more
      common forms of T2D has been slow, a number of genes have now been reproducibly
      associated with T2D risk in multiple studies. These are discussed, as well as the
      main implications that the diabetes gene discoveries will have in diabetes
      treatment and prevention.

PMID- 15842506
TI  - Impact of hormone replacement therapy on microvascular function in healthy and
      Type 2 diabetic postmenopausal women.
AB  - AIMS: Hormone replacement therapy (HRT) has been previously reported to modulate
      vascular function and cardiovascular risk. Its impact on the macrocirculation has
      previously been explored, however, little data is available on its impact on the
      microcirculation. This study aimed to determine the impact of HRT on
      microvascular function in healthy and Type 2 diabetic postmenopausal women (n=20
      and 17, respectively). METHODS: Microvascular function was assessed by skin
      maximum hyperaemia, skin hyperaemic response to iontophoretically applied
      acetylcholine (endothelial-dependent vasodilator) and sodium nitroprusside
      (endothelial-independent vasodilator), capillary pressure and the microvascular
      filtration capacity. Microvascular assessments were carried out at baseline and
      repeated following 6 months' oral hormone replacement therapy (1 mg
      oestradiol/0.5 mg norethisterone or 1 mg unopposed oestradiol for hysterectomized
      women). RESULTS: Following 6 months' therapy there were no significant changes in
      microvascular assessments in the healthy women. In the diabetic women there was a
      reduction in the skin hyperaemic response to acetylcholine [median pretreatment
      peak response: 1.95 (25th, 75th centiles: 1.54, 2.30) V vs. post-treatment peak
      response: 1.53 (1.30, 1.91) V (P=0.011, Wilcoxon's signed rank test)] and sodium
      nitroprusside [median peak response 1.59 (1.37, 1.99) vs. 1.35 (0.92, 1.63) V
      (P=0.011)] with HRT, but no other changes. CONCLUSION: These data suggests that
      HRT does not affect microvascular function in healthy women, but adversely
      affects it in diabetic women. These findings may help to explain why HRT fails to
      provide the predicted cardiovascular protection, and raises the possibility that
      HRT influences microangiopathy progression in diabetic women.

PMID- 15842507
TI  - Diabetes, hyperglycaemia and mortality in disabled older women: The Women's
      Health and Ageing Study I.
AB  - AIMS: Diabetes is associated with increased mortality in older adults, but the
      specific contributions of diabetes-associated clinical conditions and of
      increasing hyperglycaemia to mortality risk are unknown. We evaluated whether
      cardiovascular disease, comorbidities, or degree of hyperglycaemia, particularly
      severe hyperglycaemia, affected diabetes-related mortality risk in older,
      disabled women. METHODS: Six-year mortality follow-up of a random sample of 576
      disabled women (aged 65-101 years), recruited from the Medicare eligibility list
      in Baltimore (MD, USA). All-cause and cardiovascular mortality were evaluated by
      diabetes status: no diabetes; diabetes with mild, moderate, and severe
      hyperglycaemia [defined by tertiles of glycosylated haemoglobin (GHB) among women
      with diabetes]. RESULTS: Diabetes with mild, moderate, and severe hyperglycaemia
      was associated with an increased hazard rate (HR) for all-cause mortality, even
      after adjustment for demographics, risks for cardiovascular disease,
      cardiovascular and non-cardiovascular conditions, and other known mortality
      risks. A dose-response effect was suggested [mild hyperglycaemia, HR 1.81, 95%
      confidence interval (CI) 1.03, 3.17; moderate hyperglycaemia, HR 2.02, 95% CI
      1.34, 3.57; severe hyperglycaemia, HR 2.22, 95% CI 1.17, 4.25]. Women with
      diabetes had a significantly increased HR for non-cardiovascular death, but not
      for cardiovascular death, compared with those without diabetes. CONCLUSIONS:
      Diabetes, whether characterized by mild, moderate or severe hyperglycaemia,
      appears to be an independent risk factor for excess mortality in older disabled
      women and this risk may increase with increasing hyperglycaemia. This mortality
      risk is not completely explained by vascular complications, and involves non
      cardiovascular deaths. Risks and benefits of diabetes management, including
      glycaemic control and management of vascular and other comorbidities, should be
      studied in older people with complications and comorbidities.

PMID- 15842508
TI  - Predictors of first stroke in Type 1 diabetes: The Fremantle Diabetes Study.
AB  - AIMS: To examine prospectively the relationship between vascular risk factors and
      stroke in Type 1 diabetes. METHODS: A community-based sample of 126 adult Type 1
      patients was recruited between 1993 and 1996 and followed annually for a mean+/
      sd of 7.2+/-1.6 years. Cerebrovascular events before and after recruitment were
      identified from history and examination findings, hospital morbidity data and
      death notifications. RESULTS: Six patients suffered a first stroke during follow
      up, of which five were ischaemic and one a subarachnoid haemorrhage on cranial
      computed tomography. Patients were subdivided into those with no history of
      stroke/transient ischaemic attack (TIA) at baseline and no subsequent ischaemic
      stroke (Group 1, n=114), those with a history of stroke/TIA at baseline (Group 2,
      n=7), and those with no history of stroke/TIA at baseline but who suffered a
      first ischaemic stroke during follow-up (Group 3, n=5). Group 1 patients were the
      youngest, had the shortest diabetes duration and were the least likely to be
      taking antihypertensive medication or aspirin. Amongst a range of potential
      baseline predictors of first stroke including glycated haemoglobin, only serum
      HDL-cholesterol differentiated Group 3 patients (0.69+/-0.17 mmol/l) from those
      in the other groups (1.26+/-0.42 and 1.28+/-0.45 mmol/l for Groups 1 and 2
      respectively, P<0.05). CONCLUSIONS: The present association between low serum HDL
      cholesterol and ischaemic stroke patients suggests that aggressive management of
      dyslipidaemia may protect against cerebrovascular disease in Type 1 diabetes.

PMID- 15842509
TI  - Prognostic value of the Framingham cardiovascular risk equation and the UKPDS
      risk engine for coronary heart disease in newly diagnosed Type 2 diabetes:
      results from a United Kingdom study.
AB  - AIMS: To determine the prognostic value of the Framingham equation and the United
      Kingdom Prospective Diabetes Study (UKPDS) risk engine in patients with newly
      diagnosed Type 2 diabetes. METHODS: A community-based cohort (n=428; aged 30-74
      years) free of clinically evident CVD and newly diagnosed with Type 2 diabetes
      were studied over a median 4.2 (sd+/-0.62) years. Predicted (using baseline
      variables at diagnosis) and observed proportions of primary CVD and CHD events
      were compared using the Framingham equations and the UKPDS risk engine (only CHD
      events). The discrimination (c-statistic) and calibration (HLchi2) of the risk
      equations were calculated. The sensitivity and specificity of the Framingham
      equation at a 15%, 10-year CHD risk threshold (NICE guidelines) was compared with
      that of the ADA lipid threshold (LDLc>or=2.6 mmol/l or triglycerides>or=4.5
      mmol/l). RESULTS: The Framingham equations underestimated the overall number of
      cardiovascular events by 33% and coronary events by 32% and showed modest
      discrimination and poor calibration for CVD [c=0.673; HLchi2=32.8 (P<0.001)] and
      CHD risk [c=0.657; HLchi2=19.8 (P=0.011)]. Although the overall underestimate was
      lower and non-significant with the UKPDS risk engine for CHD (13%), its
      performance in terms of discrimination and calibration were similar [c=0.670;
      HLchi2=17.1 (P=0.029)]. The 15%, 10-year CHD risk threshold with both the
      Framingham and UKPDS risk engines had similar sensitivity for primary CVD as the
      lipid level threshold [85.7 and 89.8% vs. 93.9% (P=0.21 and 0.34)] and both had
      greater specificity [33.0 and 30.3% vs. 12.1% (P<0.001 and P<0.001)].
      CONCLUSIONS: In people with newly diagnosed Type 2 diabetes, both the Framingham
      equation and UKPDS risk engine are moderately effective at identifying those at
      high-risk (discrimination) and are poor at quantifying risk (calibration).
      Nonetheless, at a population level, a 15% 10-year CHD risk threshold using either
      risk calculator has similar sensitivity as an approach based on a single lipid
      risk factor level and may have benefits in terms of cost-effectiveness given the
      improved specificity.

PMID- 15842510
TI  - Abnormal ventilatory responses to hypoxia in Type 2 diabetes.
AB  - AIMS: The incidence of Type 2 diabetes is increasing, along with its associated
      micro- and macrovascular disease manifestations. Previous studies indicate that
      patients with Type 2 diabetes exhibit abnormal cardiopulmonary reflex responses
      to various stimuli, although the impact of hypoxia, a common physiological
      stimulus, on ventilatory responses has not previously been studied in humans with
      Type 2 diabetes. METHODS: Minute ventilation (V(E)) breathing pattern responses
      (total breath time, T(TOT); expiratory time, T(E); inspiratory time, T(I);
      inspiratory duty cycle, T(I)/T(TOT)) were measured during 5 min each of normoxia
      and isocapnic hypoxia (arterial O2 saturation approximately 85%) in eight
      subjects with Type 2 diabetes and seven age- and body mass index-matched healthy
      subjects. RESULTS: During normoxia, V(E) was similar in control and diabetic
      subjects (6.4+/-1.2, 6.4+/-1.1 l/min, respectively). In response to hypoxia, V(E)
      significantly increased in both groups (to 17.0+/-5.0 and 9.5+/-2.0 l/min,
      respectively, P<0.05), but the magnitude of increase in V(E) was significantly
      less in diabetic than in control subjects (P<0.05). In addition, the breathing
      pattern response to hypoxia differed between groups in terms of T(I)/T(TOT) and
      T(TOT) (P<0.05), with control subjects significantly decreasing T(TOT) and T(E)
      (P<0.05) while diabetic subjects tended to increase both. CONCLUSIONS: Relative
      to matched control subjects, Type 2 diabetic subjects exhibit blunted V(E)
      responses to acute isocapnic hypoxia, suggesting that this group of diabetic
      subjects possesses a chemoreflex ill-equipped to respond homeostatically to
      hypoxic challenge.

PMID- 15842511
TI  - Genetic association study of adiponectin polymorphisms with risk of Type 2
      diabetes mellitus in Korean population.
AB  - AIMS: To investigate any association between Type 2 diabetes mellitus and two
      single nucleotide polymorphisms (SNPs) in the adiponectin gene, T45G and G276T,
      in the Korean population. METHODS: We genotyped 427 non-diabetic controls and 493
      Type 2 diabetic patients for SNPs T45G and G276T of adiponectin gene, measured
      plasma adiponectin concentrations, and examined clinical parameters in Koreans.
      RESULTS: There were no statistically significant differences in allele
      frequencies of SNPs 45 and 276 comparing control with Type 2 diabetic subjects (T
      frequency 68.3% vs. 71.6%, P=0.13 for SNP45, G frequency 72.2% vs. 68.9%, P=0.12
      for SNP276). The genotype distributions of these SNPs had no association with the
      risk of Type 2 diabetes and metabolic parameters of insulin resistance. Plasma
      levels of adiponectin were not statistically different according to T45G and
      G276T either, in both control and Type 2 diabetic subjects. CONCLUSION: The T45G
      and G276T of the adiponectin gene may not be an important determinant of Type 2
      diabetes or insulin resistance in Korean subjects.

PMID- 15842512
TI  - Effect of diabetes mellitus and its treatment on ventricular arrhythmias
      complicating acute myocardial infarction.
AB  - AIMS: To evaluate the effect of diabetes mellitus and its treatment on the risk
      of arrhythmias among early survivors of acute myocardial infarction. RESEARCH
      DESIGN AND METHOD: The Onset Study was conducted in 64 US medical centres.
      Between August 1989 and September 1996, 3882 patients were interviewed after
      having an acute myocardial infarction. We used logistic regression models to
      examine the association of diabetes and its treatment with the risk of
      ventricular arrhythmia after adjustment for age, gender, hypertension,
      thrombolytic therapy, smoking, obesity, cardiac medicines and congestive heart
      failure. RESULTS: During the index hospitalization, patients with diabetes
      (n=814) were less likely to develop ventricular arrhythmias than patients without
      diabetes (6.8 vs. 13.3%, P<0.001). The risk of ventricular arrhythmia in patients
      treated with first generation sulphonylureas or diet alone was similar to
      patients without diabetes (OR=0.91; 95% CI, 0.39-2.15, and 0.76; 95% CI, 0.46
      1.26, respectively). However, compared with patients without diabetes, the
      adjusted odds ratio (OR) for ventricular arrhythmias was lower among patients
      treated with insulin or patients treated with second generation sulphonylureas
      (OR=0.54, 95% CI 0.32-0.92; OR=0.45, 95% CI 0.27-0.75, respectively).
      CONCLUSIONS: Compared with patients without diabetes, the risk of ventricular
      arrhythmias complicating acute myocardial infarction is lower in patients with
      diabetes treated with second generation sulphonylureas or insulin, but not in
      those treated with first generation sulphonylureas or diet alone. This suggests
      that differences in the mechanism of action of different sulphonylureas may
      result in clinically relevant differences in arrhythmic risk.

PMID- 15842513
TI  - Resistin polymorphisms are associated with cerebrovascular disease in Finnish
      Type 2 diabetic patients.
AB  - AIMS: Resistin is a hormone secreted by adipocytes and it is also expressed in
      monocytes. Resistin has been found to increase insulin resistance, a key feature
      in Type 2 diabetes. The aim of this study was to investigate whether resistin
      polymorphisms are associated with Type 2 diabetes and its clinical
      characteristics. METHODS: We studied the allele and genotype frequencies of the
      single-nucleotide polymorphisms (SNPs)-420 (C>G), +157 (T>C) and +299 (G>A) in
      the resistin gene in 258 Finnish Type 2 diabetics and 494 controls. RESULTS:
      These three markers were in significant linkage disequilibrium with each other.
      No significant (P<0.05) differences in the allele or genotype frequencies were
      observed between the study groups. Subjects with Type 2 diabetes showed a
      significant association between cerebrovascular disease and the SNPs-420
      (P=0.004) and +299 (P=0.007), the G-G and A-A genotypes, respectively, had the
      highest frequencies. SNPs-420 (P=0.000) and +299 (P=0.002) in men and SNP+157 in
      men (P=0.005) and in women (P=0.019) showed significant association with higher
      mean blood glucose. The rare allele homozygotes also had the highest mean blood
      glucose values. We also observed associations between at least one of the SNPs
      and fasting blood glucose, glycosylated haemoglobin A1 (GHbA1), low-density
      lipoprotein (LDL) cholesterol and systolic and diastolic blood pressure. After
      correction for multiple comparisons, the association between the promoter variant
      SNP-420 and cerebrovascular disease in both genders and the associations between
      mean blood glucose and SNP-420 and SNP+299 in men remained significant.
      CONCLUSIONS: The results suggest that resistin may play a role in atherogenesis
      probably through increasing insulin resistance.

PMID- 15842514
TI  - Common variants in the ATP-sensitive K+ channel genes KCNJ11 (Kir6.2) and ABCC8
      (SUR1) in relation to glucose intolerance: population-based studies and meta
      analyses.
AB  - AIMS: To evaluate the relation between common variants in the ATP-sensitive K+
      channel genes and glucose intolerance. METHODS: We conducted a meta-analysis of
      reported association studies in Caucasian populations for common variants in the
      ABCC8 (exons 16 and 18) and the KCNJ11 (E23K) gene and examined sources of
      heterogeneity in the results. The meta-analysis was based on 7768-10216 subjects
      (depending on the gene variant), and included two new population-based studies in
      the Netherlands with 725 cases and 742 controls. RESULTS: For the KCNJ11 variant,
      the summary odds ratio (OR) for glucose intolerance was 1.12 (1.01-1.23, P=0.03)
      for the EK genotype and 1.44 (1.17-1.78, P=0.0007) for the KK genotype, as
      compared with the EE genotype. For the ABCC8 exon 16 variant, the OR was 1.06
      (0.94-1.19, P=0.34) for ct and 0.93 (0.71-1.20, P=0.56) for tt, as compared with
      the cc genotype. For ABCC8 exon 18, the OR was 1.20 (0.97-1.49, P=0.10) for
      CT/TT, as compared with the CC genotype. Studies of the ABCC8 variants that were
      published first or had smaller sample sizes (for the exon 18 variant) showed
      stronger associations, which may indicate publication bias. For the ABCC8 exon 18
      and the KCNJ11 variant, associations were stronger for studies of clinical
      diabetes than newly detected glucose intolerance. The population attributable
      risk for clinical Type 2 diabetes was 6.2% for the KCNJ11 KK genotype and 10.1%
      for the KCNJ11 EK and KK genotype combined. CONCLUSIONS: The common KCNJ11 E23K
      gene variant, but not the ABCC8 exon 16 or exon 18 variant, was consistently
      associated with Type 2 diabetes.

PMID- 15842515
TI  - A multivariate logistic regression equation to screen for dysglycaemia:
      development and validation.
AB  - AIMS: To develop and validate an empirical equation to screen for dysglycaemia
      [impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and undiagnosed
      diabetes]. METHODS: A predictive equation was developed using multiple logistic
      regression analysis and data collected from 1032 Egyptian subjects with no
      history of diabetes. The equation incorporated age, sex, body mass index (BMI),
      post-prandial time (self-reported number of hours since last food or drink other
      than water), systolic blood pressure, high-density lipoprotein (HDL) cholesterol
      and random capillary plasma glucose as independent covariates for prediction of
      dysglycaemia based on fasting plasma glucose (FPG)>or=6.1 mmol/l and/or plasma
      glucose 2 h after a 75-g oral glucose load (2-h PG)>or=7.8 mmol/l. The equation
      was validated using a cross-validation procedure. Its performance was also
      compared with static plasma glucose cut-points for dysglycaemia screening.
      RESULTS: The predictive equation was calculated with the following logistic
      regression parameters: P=1+1/(1+e-X)=where X=-8.3390+0.0214 (age in years)+0.6764
      (if female)+0.0335 (BMI in kg/m2)+0.0934 (post-prandial time in hours)+0.0141
      (systolic blood pressure in mmHg)-0.0110 (HDL in mmol/l)+0.0243 (random capillary
      plasma glucose in mmol/l). The cut-point for the prediction of dysglycaemia was
      defined as a probability>or=0.38. The equation's sensitivity was 55%, specificity
      90% and positive predictive value (PPV) 65%. When applied to a new sample, the
      equation's sensitivity was 53%, specificity 89% and PPV 63%. CONCLUSIONS: This
      multivariate logistic equation improves on currently recommended methods of
      screening for dysglycaemia and can be easily implemented in a clinical setting
      using readily available clinical and non-fasting laboratory data and an
      inexpensive hand-held programmable calculator.

PMID- 15842516
TI  - Insulin aspart improves meal time glycaemic control in patients with Type 2
      diabetes: a randomized, stratified, double-blind and cross-over trial.
AB  - AIMS: This randomized, multi-centre, double-blind, stratified, two period, cross
      over trial was undertaken to assess the pharmacokinetics and pharmacodynamics of
      insulin aspart injected immediately before compared with regular human insulin
      injected 30 min before a Mediterranean-style meal in 37 (23 M, 14 F) patients
      with Type 2 diabetes. METHODS: Insulin aspart or regular human insulin was given
      subcutaneously (0.15 U/kg) in random sequence, using a double-dummy technique (at
      one visit: human regular insulin at t=-30 min and placebo at t=0; at the other
      visit: placebo at t=-30 min and aspart insulin at t=0). Serum glucose and insulin
      concentrations (15 points) were measured after each meal for 240 min. RESULTS:
      Post-prandial glycaemic excursions were 20% lower with insulin aspart (IAsp)
      compared with regular human insulin (HI) treatment [ratio (Iasp/HI)=0.80,
      CI=(0.66-0.98), P=0.034]. The maximum serum glucose (SG) concentration was
      similar for the two treatments (P=NS). The (median) time to maximum SG was 25 min
      shorter for IAsp compared with HI (P=0.048). Maximum serum insulin concentration
      was higher after IAsp compared with HI (P=0.023) as well as the area under the 4
      h serum insulin curve (P=0.006). Furthermore, the time to maximum serum insulin
      concentration was 27 min shorter after IAsp (P=0.039), even though IAsp was
      injected 30 min after HI. No adverse events occurred during the trial.
      CONCLUSIONS: In patients with Type 2 diabetes a more favourable insulin profile
      and a better glycaemic control were found with IAsp injected immediately before
      compared with HI injected 30 min before a Mediterranean-style meal.

PMID- 15842517
TI  - A randomized study of orlistat in combination with a weight management programme
      in obese patients with Type 2 diabetes treated with metformin.
AB  - AIMS: To assess the effects of orlistat vs. placebo, in combination with a weight
      management programme, on weight loss and metabolic control in obese patients with
      Type 2 diabetes. METHODS: Patients treated with either metformin alone or
      metformin in combination with sulphonylurea were randomized to double-blind
      treatment with orlistat or placebo (120 mg) three times daily, combined with a
      mildly reduced calorie diet and a weight management programme for 52 weeks.
      Changes in body weight, anthropometry, glycaemic control and lipid profile were
      assessed. RESULTS: After 52 weeks, orlistat-treated patients achieved an almost
      threefold greater reduction in weight compared with placebo recipients (-5.0% vs.
      -1.8%; P<0.0001). The decrease in waist circumference was significantly greater
      with orlistat than placebo (-4.8 cm vs. -2.8 cm; P=0.0022). Orlistat treatment
      was also associated with significantly greater reductions in haemoglobin A(1c) (
      1.1% vs. -0.2%; P<0.0001), fasting plasma glucose (-1.9 mmol/l vs. -0.3 mmol/l;
      P<0.0001), total cholesterol (-0.2 mmol/l vs. 0.1 mmol/l; P=0.03) and
      apolipoprotein B (-0.08 g/l vs. 0.01 g/l; P=0.0085) and greater improvements in
      beta-cell function (P=0.031) and insulin resistance (P=0.001) assessed using the
      homeostasis model assessment (HOMA). Similar results were obtained for subgroups
      of patients treated with metformin alone or metformin in combination with
      sulphonylurea. Orlistat treatment reduced the requirement for anti-diabetic
      medication more than placebo. CONCLUSIONS: Orlistat, in combination with a
      reduced calorie diet and a weight management programme, promotes weight loss and
      clinically relevant improvements in glycaemic control and other cardiovascular
      risk factors in obese patients with Type 2 diabetes.

PMID- 15842518
TI  - Changing patterns of primary care for diabetes in Trinidad and Tobago over 10
      years.
AB  - OBJECTIVE: To evaluate standards of preventive medical care for Type 2 diabetes
      in the context of high prevalence and limited resources. METHODS: Surveys of
      records for diabetic subjects attending 23 government primary care health centres
      in Trinidad and Tobago in 2003 and 1998 and nine health centres in 1993. Records
      were compared by study year for blood glucose and blood pressure, surveillance
      for complications, appropriate management advice and drug prescriptions. Relevant
      interventions included new clinical guidelines, training workshops for clinical
      staff and reports to the Ministry of Health. During this time, investment in
      primary care increased in the context of health sector reform policies and a
      favourable macroeconomic environment. RESULTS: Comparing 1993 with 2003, the
      proportion with a blood glucose test in the past 12 months increased from 33% to
      91%, urea or creatinine ever recorded increased from 14% to 61%, diet advice
      recorded in the first 12 months of follow-up from 35% to 67%, exercise advice
      from 3% to 61%. The proportion prescribed metformin increased from 25% to 65%,
      while chlorpropamide decreased from 48% to 0%. The proportion of all subjects
      treated with antihypertensive drugs increased from 49% to 70%, and the proportion
      of treated patients prescribed angiotensin-converting enzyme inhibitors increased
      from 8% to 72%. Most recent ever records of blood glucose, blood pressure and
      body weight showed no decrease. CONCLUSIONS: Repeated surveillance of processes
      of care provided information to stimulate and plan change. Process changes were
      associated with intervention at several levels and increased availability of
      resources.

PMID- 15842519
TI  - Lifetime risk of symptomatic carpal tunnel syndrome in Type 1 diabetes.
AB  - AIMS: To determine the lifetime risk of developing symptomatic carpal tunnel
      syndrome (CTS) in subjects with Type 1 diabetes and to investigate the effect of
      glycaemic control, body mass index (BMI), gender and age of onset of diabetes.
      METHODS: One hundred and twenty-two consecutive subjects with Type 1 diabetes
      seen by a single investigator, over 1-year, were questioned about previous
      surgery for, or current symptoms of CTS. Those with current symptoms were
      referred for nerve conduction studies (NCS). Those with previous surgery and/or
      diagnostic NCS were classified as having CTS. Lifetime risk was calculated by the
      Kaplan-Meier method. RESULTS: Twenty six out of 122 patients had CTS, 18 of whom
      (69%) had undergone median nerve decompression surgery. The predicted lifetime
      risk of CTS reached 85% after 54 years of Type 1 diabetes (95% confidence
      interval: 72-97%). The duration of diabetes was greater in those who had
      developed CTS than in those who had not (29 vs. 19 years, P=0.0001). In those
      diagnosed with diabetes before the age of 20 there was a lag time of at least 19
      years before the development of CTS, whereas patients with later onset of
      diabetes, began to develop CTS from as early as 5 years diabetes duration. There
      was no demonstrable effect of glycaemic control, obesity, gender or retinopathy
      on the appearance of CTS. CONCLUSION: The lifetime risk of developing symptomatic
      CTS with Type 1 diabetes is high, and is related to age and duration of diabetes,
      but not to the development of microvascular complications.

PMID- 15842520
TI  - Rodent bites on the feet of diabetes patients in Tanzania.
AB  - AIM: To characterize the epidemiology of rodent bite foot injuries in patients
      presenting to a diabetes clinic in Tanzania. METHODS: During July 1998-September
      2003, all adult diabetes patients presenting with rodent bite injuries were
      identified. Follow-up included antimicrobial therapy and surgery, where
      appropriate. RESULTS: All 34 patients with rodent bites had Type 2 diabetes and
      peripheral neuropathy. Median age was 55.5 years; 62% were male. All bites
      occurred during sleep. The median time between acquiring the bite and
      presentation to MNH was 7 (range: 1-17) days. Patients who delayed seeking
      medical attention were significantly more likely to develop gangrene. Seventeen
      patients underwent minor or major amputation. Complete healing occurred in 30
      (88%) patients; four patients died. CONCLUSION: Diabetes patients with peripheral
      neuropathy are at increased risk of bite injuries in areas with large rodent
      populations. Preventive efforts should include covering the feet at bedtime, and
      daily feet examination by patient or relatives.

PMID- 15842521
TI  - Continuing metformin when starting insulin in patients with Type 2 diabetes: a
      double-blind randomized placebo-controlled trial.
AB  - AIMS: To test the effect of continuing metformin on weight gain and glycaemic
      control in patients with poorly controlled Type 2 diabetes who need to start
      insulin. METHODS: Patients with Type 2 diabetes on maximum tolerated oral agents
      referred for insulin conversion were recruited from hospital diabetes clinics
      into a double-blind randomized placebo-controlled trial. The 183 participants
      received metformin or placebo, titrated up to 2 g a day or maximum tolerated
      dose, with insulin started according to local practice. The main outcome measures
      were weight change over 12 months, HbA1c, insulin dose, frequency of
      hypoglycaemia, treatment satisfaction, and well-being. RESULTS: Over 12 months,
      metformin was associated with less weight gain than placebo [mean 6.1 kg vs. 7.6
      kg; adjusted difference 1.5 kg (95% confidence interval 0.2-2.9); P=0.02], a
      greater reduction in HbA1c[1.5% vs. 1.3%; adjusted difference 0.5% (0.1-0.9);
      P=0.02] and a lower insulin requirement [62 units vs. 86; adjusted difference 25
      units (15-34); P<0.001], but also more hypoglycaemia [relative risk of any
      episode 1.24 (1.02-1.1); P=0.03]. Treatment satisfaction improved more in
      patients on metformin than on placebo (P<0.001), as did the positive well-being
      score (P=0.02). CONCLUSIONS: Metformin decreases weight gain, lowers insulin
      requirement, and improves glycaemic control, and should be continued in patients
      with Type 2 diabetes who transfer to insulin.

PMID- 15842522
TI  - A case of novel de novo paired box gene 6 (PAX6) mutation with early-onset
      diabetes mellitus and aniridia.
AB  - BACKGROUND: Paired box gene 6 (PAX6) is a transcription factor involved in eye
      development. Mutations of PAX6 cause congenital eye anomalies, such as aniridia.
      PAX6 is also involved in the development of the endocrine pancreas, and reported
      to be a genetic factor common to aniridia and glucose intolerance, although the
      latter is usually mild. Here, we describe a case of PAX6 mutation with early
      onset diabetes mellitus. CASE REPORT: A 27-year-old woman was referred to our
      clinic. She was diagnosed having diabetes at the age of 15 with negative glutamic
      acid decarboxylase (GAD) antibody. Insulin treatment was started at age 24.
      Because she had aniridia, PAX6 gene mutation was investigated and a heterozygous
      2-bp deletion (c.402del2) was identified. Her parents did not have aniridia and
      PAX6 mutations. Heterozygous PAX6 mutation may cause glucose intolerance.
      However, cases of early-onset diabetes mellitus have not been reported. Her
      parents did not have diabetes, but their insulinogenic indices were low (0.25 and
      0.3, respectively). We thought her early-onset diabetes was partly as a result of
      PAX6 mutation and partly because of an unknown insulin secretory defect inherited
      from her parents. We could not find any mutations in HNF-1alpha, -1beta, -4alpha,
      IPF-1, ISL-1, BEAT2/NeuroD1, PAX4, and amylin genes. CONCLUSIONS: We report a
      case of PAX6 gene mutation with early-onset diabetes mellitus and aniridia. Low
      insulin secretory capacity in her parents suggested that her insulin secretory
      defect is as a result of not only PAX6 mutation but other genetic factors
      inherited from her parents.

PMID- 15842523
TI  - Childhood diabetes presenting with hyperosmolar dehydration but without
      ketoacidosis: a report of three cases.
AB  - BACKGROUND: Diabetic ketoacidosis (DKA) is a common mode of presentation of
      diabetes mellitus in children, accounting for 26% of new cases. Rarely, children
      with diabetes may develop other forms of metabolic decompensation associated with
      hyperglycaemia and hyperosmolality. Hyperglycaemia and hyperosmolality without
      ketoacidosis has high mortality in adults, although there is no data on mortality
      in children. CASE REPORTS: We describe three children who presented to Birmingham
      Children's Hospital and were initially suspected to have DKA. Each child was
      severely hyperglycaemic and hyperosmolar but without significant ketosis or
      acidosis. In two of the three children, the hyperosmolar state was associated
      with the ingestion of large volumes of high calorie fluids preceding the
      presentation. These children were exquisitely sensitive to insulin and may be at
      a significantly higher risk of cerebral oedema in view of their hyperosmolar
      state. CONCLUSIONS: Hyperosmolar hyperglycaemia is a serious and rare
      complication at presentation of diabetes in children, and should be distinguished
      from DKA. These children are at an increased risk of cerebral oedema compared
      with DKA, and one should have a low threshold for suspicion of this complication.

PMID- 15842524
TI  - Insights into the acute cerebral metabolic changes associated with childhood
      diabetes.
AB  - AIMS: Type 1 diabetes is a prevalent chronic disease in childhood with the
      commonest single cause of death being cerebral oedema in the context of diabetic
      ketoacidosis (DKA). The nature of the alterations in cerebral metabolism that may
      result in vulnerability to neuronal injury remains unknown. The aim of this study
      was to analyse the magnetic resonance imaging (MRI) and magnetic resonance
      spectroscopy (MRS) brain data from eight children with diabetes following acute
      presentation with hyperglycaemia with or without ketoacidosis, to determine the
      nature and timing of any alterations in cerebral structure and metabolism.
      METHODS: This study used MRI and MRS to investigate regional cerebral
      abnormalities in a small series of diabetic patients with and without DKA.
      Changes were compared with the clinical and biochemical features of the patients
      studied. RESULTS: Our small series of patients all demonstrated abnormal signal
      changes in the frontal region on fluid attenuated inversion recovery (FLAIR) MR
      imaging, suggestive of oedema, and spectroscopic abnormalities of increased
      taurine, myoinositol and glucose levels. The MR abnormalities varied in severity
      but did not correlate with any clinical or biochemical parameters. CONCLUSIONS:
      These changes indicate that many diabetic children, particularly at presentation,
      may have alterations in cerebral metabolism with implications for the
      pathogenesis and treatment of the cerebral complications of DKA. In addition, our
      findings suggest that increased taurine may be one of the important
      differentiating factors in the response of the brain of diabetic children to DKA
      that may reflect an increase in their vulnerability to cerebral oedema compared
      with diabetic adults.

PMID- 15842525
TI  - Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2
      diabetes.
AB  - AIMS: Glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP)
      are important insulinotropic hormones that enhance the insulin secretory response
      to feeding. Their potential for treating Type 2 diabetes is limited by short
      biological half-life owing to degradation by dipeptidyl peptidase IV (DPP IV). We
      investigated the acute effects of metformin on DPP IV activity in Type 2 diabetes
      to elucidate inhibition of DPP IV as a possible mechanism of action. METHODS:
      Eight fasting subjects with Type 2 diabetes (5M/3F, age 53.1+/-4.2 years, BMI
      36.8+/-1.8 kg/m2, glucose 8.9+/-1.2 mmol/l, HbA1c 7.8+/-0.6%) received placebo or
      metformin 1 g orally 1 week apart in a random, crossover design. RESULTS:
      Following metformin, DPP IV activity was suppressed compared with placebo (AUC0-6
      h 3230+/-373 vs. 5764+/-504 nmol ml/l, respectively, P=0.001). Circulating
      glucose, insulin and total GLP-1 were unchanged. Metformin also concentration
      dependently inhibited endogenous DPP IV activity in vitro in plasma from Type 2
      diabetic subjects. CONCLUSION: Oral metformin effectively inhibits DPP IV
      activity in Type 2 diabetic patients, suggesting that the drug may have potential
      for future combination therapy with incretin hormones.

PMID- 15842526
TI  - Awareness and use of smoking cessation treatments among diabetic patients.
AB  - AIMS: To investigate awareness of pharmacotherapeutic aids to smoking cessation
      in diabetic cigarette smokers. METHODS: A structured questionnaire-based
      interview was held by a research nurse individually with consecutively attending
      cigarette smokers. RESULTS: Of 597 diabetic patients attending a routine clinic,
      100 (17%) were current cigarette smokers. Mean (+/-sd) age was 58+/-11 years, 58%
      were male, and 96% Type 2 diabetic patients. Mean daily cigarette consumption was
      16/day, for a mean duration of 35 years. There were 34% who had never heard of
      nicotine replacement therapy (NRT), and of those who had, only 49% considered it
      safe with diabetes. Bupropion (Zyban) was unknown to 46%, and of those who knew
      of it, 39% thought it unsafe in diabetic patients. Only 31% of the group had been
      previously offered NRT, and 14% bupropion. The NHS Quitline was known of by 84%,
      but only 8% had used it. CONCLUSIONS: Cigarette smokers with diabetes have poor
      uptake, awareness and knowledge of NRT and bupropion as aids to smoking
      cessation. They comprise a high-risk group, for large and small vessel disease,
      and these findings are therefore of concern. More active education and support
      for these patients by medical and nursing staff is needed.

PMID- 15842527
TI  - Interleukin-12B gene polymorphism is assoicated with circulating oxidized LDL
      levels in Japanese Type 2 diabetic patients.

PMID- 15842529
TI  - Type 2 diabetes and hearing loss in black Africans.

PMID- 15842528
TI  - Patients with Type 2 diabetes treated with metformin: prevalence of
      contraindications and their correlation with discontinuation.

PMID- 15842530
TI  - Cardiovascular therapies and their role in diabetic eye disease.

PMID- 15842531
TI  - Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory
      blood pressure in subjects with impaired glucose tolerance: does it really work?
      If yes, is it a novelty?

PMID- 15842537
TI  - Long-term use of cyclosporine in the treatment of canine atopic dermatitis.
AB  - This retrospective study of 51 dogs with atopic dermatitis (AD) treated with
      cyclosporine (CsA) for a minimum of 6 months assessed the frequency of dosing and
      the need for continual treatment to control clinical signs. The study evaluated
      both medical records and information supplied by the owners in the form of
      written questionnaires and telephone follow-up. Laboratory parameters, possible
      adverse effects and owner satisfaction were assessed. The dose of CsA was 5 mg/kg
      orally per day and dogs received CsA for 6-30 months. At the conclusion of the
      study period, 28 dogs (55%) needed ongoing CsA to control clinical signs of AD: 8
      (15%) received CsA 2-3 days per week, 10 (20%) 4-5 days per week, and 10 (20%)
      daily. CsA was discontinued in 23 dogs (45%) after 6-24 months due to either a
      limited response (22%) or after achieving a clinical response (24%). The results
      suggest that some dogs with AD treated with CsA may not require daily or even
      ongoing treatment to control clinical signs. Laboratory abnormalities were
      detected in 13 dogs (25%) during their CsA treatment. Two dogs developed oral
      growths and three developed hirsuitism. Forty owners (78%) reported no adverse
      events in their dogs during the treatment period. Thirty-six owners (71%) were
      satisfied with CsA as treatment for their atopic dog.

PMID- 15842538
TI  - Acral mutilation and analgesia in 13 French spaniels.
AB  - Acral mutilation and analgesia (AMA) is reported in 13 French spaniels in Canada.
      This newly recognized disorder shares striking similarities in clinical features
      and biopsy findings to the other acral mutilation syndromes or hereditary sensory
      neuropathies reported in German short-haired pointer dogs, English pointer dogs
      and English springer spaniels. Clinical signs are first noted between 3.5 and 12
      months of age. Affected dogs lick, bite and severely self-mutilate their distal
      extremities resulting in ulcers with secondary bacterial infection. Auto
      amputation of claws, digits and footpads occurs in severe cases. Single or
      multiple feet can be affected. Affected dogs walked on their severely mutilated
      feet without evidence of pain, lameness, or ataxia. The majority of the dogs were
      euthanized within days to months of diagnosis.

PMID- 15842539
TI  - Immunoglobulin E-bearing cells and mast cells in skin biopsies of horses with
      urticaria.
AB  - The pathogenesis of equine urticaria is not well understood. In man, urticaria
      has been associated with immunological and nonimmunological mechanisms leading to
      the release of various mediators by mast cells. Skin biopsies of 32 horses with a
      history of urticaria were stained with toluidine blue, a double-labelling method
      for chymase and tryptase, and immunohistochemistry for immunoglobulin (Ig)E.
      These horses were compared with horses with pemphigus foliaceus, insect bite
      hypersensitivity and control horses with healthy skin. Neither formalin fixation
      time nor biopsy site influenced the staining methods. No chymase-positive cells
      were found. In all groups of horses, cells staining with toluidine blue and for
      tryptase and IgE were found in the epidermis and hair follicle papilla and
      significantly more positively staining cells were observed in the subepidermal
      dermis compared with the deep dermis. Horses with urticaria had significantly
      more IgE-bearing cells in the subepidermal dermis than control horses. However,
      horses with urticaria had significantly fewer toluidine-blue-stained mast cells
      in both subepidermal and deep dermis compared with the insect bite
      hypersensitivity and pemphigus foliaceus groups. This study suggests that IgE
      mediated reactions play a role in the pathogenesis of urticaria.

PMID- 15842540
TI  - Development of an enzyme-linked immunosorbant assay (ELISA) for the serodiagnosis
      of canine dermatophytosis caused by Microsporum canis.
AB  - Abstract In dogs, dermatophytosis should be considered in any case of alopecic,
      papular or pustular lesion. The aim of this study was to develop an enzyme-linked
      immunosorbant assay (ELISA) as an aid in the diagnosis of canine dermatophytosis.
      The antigen used was a whole fungal extract obtained from an isolate of
      Microsporum canis cultured on a liquid medium from the parasitized hair of a cat
      with patches of alopecia. To assess the ELISA performances, sera from 18 dogs
      with dermatophytosis caused by M. canis (group A, n = 18), 20 dogs with skin
      diseases other than dermatophytosis and 22 healthy dogs (group B, n = 42) were
      tested. Four further animals were tested: three with dermatophytosis caused by M.
      gypseum and one by T. mentagrophytes. A significant difference (P < 0.01,
      Wilcoxon's test, w = 364) was found between IgG-specific levels of sera of
      recently M. canis-infected dogs (infection < 15 days) and controls (although
      three dogs had negative titres at this stage). A highly significant difference (P
      < 0.001, w = 462) was noted between controls and dogs with infection of longer
      duration (> 30 days). All dogs had positive titres at this stage. A highly
      significant correlation (P < 0.001, Spearman's test, rho = 0.86) between duration
      of infection and IgG concentration was noted. The test has good sensitivity
      (83.3%) and high specificity (95.2%) but some dogs retained positive titres after
      elimination of infection. The sensitivity is higher than that of direct
      microscopic hair examination and similar to that of fungal culture with DTM
      (dermatophyte test medium).

PMID- 15842541
TI  - Heat shock proteins expression in canine intracutaneous cornifying epithelioma
      and squamous cell carcinoma.
AB  - Heat shock proteins (HSPs) are strongly implicated in the control of cell growth,
      differentiation and biological behaviour of many human cutaneous neoplasms. To
      our knowledge, no data have been published in the veterinary literature
      concerning either normal or neoplastic skin. In this study, the
      immunohistochemical expression of Hsp27, Hsp72 and Hsp73 was evaluated in normal
      canine skin, 14 intracutaneous cornifying epitheliomas (ICE), 10 well
      differentiated and 5 moderately differentiated squamous cell carcinomas (SCC).
      Expression was correlated with the histological degree of keratinocyte
      differentiation and proliferation, and investigated as to its usefulness in the
      differential diagnosis of these canine tumours. In normal epidermis, Hsp27
      exhibited cytoplasmic labelling in the spinous and granular layers, whereas in
      neoplastic tissues it was detected particularly in those areas showing squamous
      differentiation. Hsp72 immunoreactivity was more intense in ICE and well
      differentiated SCC than in normal skin; however, reduced immunolabelling was
      observed in moderately differentiated SCC. Unlike Hsp72, Hsp73 showed less
      intense labelling in ICE and well-differentiated SCC than in normal epithelium
      and an increased positivity in moderately differentiated SCC. These results
      indicate that HSP immunoreactivity differs between normal and neoplastic canine
      skin. Hsp27 expression seems to correlate directly with cellular differentiation;
      by contrast, the involvement of Hsp72/73 in proliferation and differentiation of
      tumour cells remains controversial. The pattern and intensity of immunolabelling
      of each investigated HSP did not show, however, significant differences between
      ICE and SCC; therefore, they do not seem to be useful in the differential
      diagnosis of these two canine tumours.

PMID- 15842542
TI  - Evaluation of a point-of-care immunodot assay for predicting results of allergen
      specific intradermal and immunoglobulin E serological tests.
AB  - Immunotherapy to prevent recurrence of clinical signs of atopic dermatitis (AD)
      is based on intradermal or serological tests that assist in identifying allergen
      specific immunoglobulin E hypersensitivities. Unfortunately, the results of such
      tests can be negatively influenced by several factors, which include the age of
      the patients, the season of testing and the administration of anti-allergic
      drugs. Screening to predict when these expensive tests will be useful would
      benefit owners of dogs with AD. The objectives of this study were to determine
      whether a point-of-care allergen-specific immunodot assay (Allercept E-Screen,
      Heska Corp., Ft Collins, CO, USA) could predict results of either intradermal or
      Allercept full panel serological tests in atopic dogs. Thirty dogs living in the
      south-eastern USA were diagnosed with AD in accordance with current standards.
      Allergen-specific intradermal, serological and E-Screen tests were performed in
      all subjects. For flea, house dust mite and pollen allergens altogether, results
      of the E-Screen assay agreed with those of intradermal and serological tests in
      26/30 dogs (87%) and 25/30 dogs (83%), respectively. In this group of dogs, the
      probabilities of obtaining intradermal or serological tests positive for these
      allergens were 70 and 67%, respectively. If either skin or serum tests were
      performed only in dogs with positive E-Screen tests, the probability of obtaining
      positive results would be increased from 70 to 95% and from 67 to 90%,
      respectively. In this population of dogs with AD, results of the E-Screen point
      of-care immunodot assay was found to often agree with those of allergen-specific
      intradermal or Allercept tests for selected allergen groups.

PMID- 15842543
TI  - Cutaneous extraskeletal mesenchymal chondrosarcoma in a cat.
AB  - A 4-year-old, male cat was presented with a fixed, subcutaneous mass in the
      lumbosacral region. A histopathological examination revealed a well-defined but
      nonencapsulated neoplasm characterized by a proliferation of predominantly
      spindle cells, with high mitotic activity. Interspersed between these cells were
      single cellular elements with chondroid differentiation. Large areas of
      cartilaginous tissue with foci of endochondral ossification, necrosis and myxoid
      tissue were also observed within the neoplastic parenchyma. A diagnosis of
      extraskeletal mesenchymal chondrosarcoma was made based on the histological
      pattern - characterized by the coexistence of cartilaginous islands and
      undifferentiated mesenchymal cells, results of Alcian blue staining at various
      pH, immunohistochemical reactivity against vimentin and S-100, and the absence of
      skeletal involvement or other primary tumour sites. Clinical history of the cat
      excluded traumas, vaccinations or other types of subcutaneous inoculation. Six
      months on from surgical treatment, neither recurrence nor metastases have been
      detected.

PMID- 15842544
TI  - Hereditary equine regional dermal asthenia in three related Quarter horses in
      Brazil.
AB  - Hereditary equine regional dermal asthenia belongs to a group of inherited,
      congenital connective tissue dysplasias usually described as hyperelastosis
      cutis, cutaneous asthenia, dermatosparaxis, or Ehlers-Danlos-like syndrome. This
      report presents the clinical and histological features of three related Quarter
      horses affected with regional dermal asthenia. These horses had bilateral
      asymmetric lesions of the trunk and lumbar regions, where the skin was
      hyperextensible. Handling of the skin elicited a painful response and superficial
      trauma led to skin wounds. The skin was thinner than normal in the affected
      areas, with thickened borders and harder fibrotic masses (pseudotumours). The
      histopathological findings included thinner and smaller collagen fibrils, and a
      loose arrangement of collagen fibres in the middle, adventitial and deep dermis.
      Masson's trichrome and Calleja stains did not reveal any abnormality of collagen
      and elastic fibres. Electron microscopy showed no abnormalities. As in human
      patients, pseudotumour histopathological findings included fibroplasia and
      neovascularization. The pedigree chart of these animals supports an autosomal
      recessive type of inheritance, which has been suggested by other studies. This is
      the first report of this disease in Brazil. Its clinical and histological
      features resemble those described in horses affected with this condition in the
      United States.

PMID- 15842545
TI  - Feline cutaneous toxoplasmosis: a case report.
AB  - A 9-year-old female, domestic short hair cat was presented with sudden onset of
      polyuria/polydipsia, and hundreds of cutaneous nodules. Prior to referral, the
      cat had had four skin nodules that were treated with steroids. The four skin
      nodules then multiplied to form more than 100 ulcerated and nonulcerated nodules
      located all over the trunk. Clinical evaluation revealed hypothermia and
      respiratory distress. Cytology from both skin nodules and bronchoalveolar lavage
      showed macrophages and small organisms whose shape and size were indicative of
      Toxoplasma spp., or similar organisms. Feline immunodeficiency virus (FIV) and
      feline leukaemia virus (FeLV) serology results were negative. The cat was
      seropositive for Toxoplasma (IgG 1 : 640) and Neospora (1 : 80) infections. The
      cat died soon after referral. Necropsy revealed pyothorax, necrotic/purulent
      pneumonia, haemorrhagic spots on kidneys and mesentery. Histopathology from skin
      nodules showed diffuse, deep necrotic dermatitis/panniculitis, vasculitis and
      disseminated free and grouped protozoa. The parasites were found in lungs,
      spleen, kidneys and liver. Immunohistochemistry on skin tissue with anti
      Toxoplasma gondii and Neospora caninum antibodies gave positive results with
      both. Electron microscopy showed single and grouped tachyzoites with
      morphological features of T. gondii, often within macrophages. Samples of
      cutaneous nodules and bronchoalveolar fluid were examined by a polymerase chain
      reaction (PCR) assay for detecting apicomplexa coccidia. PCR results were
      consistent only with T. gondii infection. Therefore, immunohistochemistry
      positivity for N. caninum was considered a cross-reaction and a diagnosis of
      cutaneous and visceral toxoplasmosis was made.

PMID- 15842546
TI  - Biomarkers and surrogate endpoints.

PMID- 15842547
TI  - Biomarkers for the effects of selective serotonin reuptake inhibitors (SSRIs) in
      healthy subjects.
AB  - AIMS: Studies of novel centrally acting drugs in healthy volunteers are
      traditionally concerned with kinetics and tolerability, but useful information
      may also be obtained from biomarkers of clinical endpoints. This paper provides a
      systematic overview of CNS-tests used with SSRIs in healthy subjects. A useful
      biomarker should meet the following requirements: a consistent response across
      studies and drugs; a clear response of the biomarker to a therapeutic dose; a
      dose-response relationship; a plausible relationship between biomarker,
      pharmacology and pathogenesis. METHODS: These criteria were applied to all
      individual tests found in studies of selective serotonin reuptake inhibitors
      (SSRIs), performed in healthy subjects since 1966, identified with a systematic
      MedLine search. Separate databases were created to evaluate the effects of single
      or multiple dose SSRI-studies, and for amitriptyline whenever the original report
      included this antidepressant as a positive control. Doses of the antidepressant
      were divided into high- and low-dose ranges, relative to a medium range of
      therapeutic doses. For each test, the drug effects were scored as statistically
      significant impairment/decrease (-), improvement/increase (+) or no change (=)
      relative to placebo. RESULTS: 56 single dose studies and 22 multiple dose studies
      were identified, investigating the effects of 13 different SSRIs on 171 variants
      of neuropsychological tests, which could be clustered into seven
      neuropsychological domains. Low single doses of SSRIs generally stimulated tests
      of attention and memory. High doses tended to impair visual/auditory and
      visuomotor systems and subjective performance, while showing an acceleration in
      motor function. The most pronounced effects were observed using tests that
      measure flicker discrimination (improvement at low doses: 75%, medium doses: 40%,
      high doses: 43% of studies); REM sleep (inconsistent decrease after medium doses,
      decrease in 83% of studies after high doses); and EEG recordings, predominantly
      in alpha (decrease in 60% and 43% of studies after low and medium doses,
      respectively) and in theta activity (increase in 43% and 33% of studies after
      medium and high doses, respectively). Amitriptyline generally impaired central
      nervous system (CNS) functions, which increased with doses. Multiple doses caused
      less pronounced effects on the reported tests. The most responsive tests to
      amitriptyline appeared to be EEG alpha and theta, and REM sleep duration.
      CONCLUSIONS: SSRIs in healthy subjects appear to cause slight stimulating effects
      after low doses, which tend to diminish with dose. The most consistent effects
      were observed with flicker discrimination tests, EEG (alpha and beta bands), REM
      sleep duration, and subjective effects at higher doses. These effects are small
      compared with amitriptyline and other CNS-active drugs. Multiple dosing with
      SSRIs caused even fewer measurable differences from placebo, probably due to
      adaptive processes. SSRI-effects are best detected with a test battery that is
      sensitive to general CNS-stimulation, but such tests only comprise a very small
      portion of the close to 200 different methods that were found in current review.

PMID- 15842548
TI  - Laser Doppler imager (LDI) scanner and intradermal injection for in vivo
      pharmacology in human skin microcirculation: responses to acetylcholine,
      endothelin-1 and their repeatability.
AB  - AIMS: The purpose of this study was to evaluate the repeatability of forearm skin
      blood flow responses to intradermal injections of acetylcholine (ACh) and
      endothelin-1 (ET-1) using a double injection technique (DIT) and a laser Doppler
      imager (LDI) scanner in the human skin microcirculation. METHODS: We used a laser
      Doppler imager (Moor LDI V3.01) to continuously monitor the change in skin blood
      flow during intradermal administration of physiological saline (0.9% NaCl),
      acetylcholine (ACh 10(-7), 10(-8), 10(-9) M) and endothelin-1 (ET-1 10(-14), 10(
      16), 10(-18) M) in 10 healthy male subjects. Subjects were examined on 3
      different days for assessment of interday and interobserver repeatability.
      Injections of either drug were randomly placed on different sites of the forearm.
      Laser Doppler images were collected before and after injection at 2.5 min
      intervals for 30 min. Data were analysed after the completion of each experiment
      using Moor Software V.3.01. Results are expressed as changes from baseline in
      arbitrary perfusion units (PU). RESULTS: ACh caused a significant vasodilation (P
      < 0.0001 anova, mean +/- SE: 766 +/- 152 PU, ACh 10(-9) M; 1868 +/- 360 PU, ACh
      10(-8) M; 4188 +/- 848 PU, ACh 10(-7) M; mean of days 1 and 2, n = 10), and ET-1
      induced a significant vasoconstrictive response (P < 0.0001 anova, -421 +/- 83
      PU, ET-1 10(-18) M; -553 +/- 66 PU, ET-1 10(-16) M; -936 +/- 90 PU, ET-1 10(-14)
      M; mean of days 1 and 2, n = 10). There was no difference on the response to
      either drug on repeated days. Bland-Altman analyses showed a close agreement of
      responses between days with repeatability coefficients of 1625.4 PU for ACh, and
      386.0 PU for ET-1 (95% CI: ACh, -1438 to 1747 PU, ET-1, -399 to 358 PU) and
      between observers with repeatability coefficients of 1057.2 PU for ACh and 255.8
      PU for ET-1 (95% CI: ACh, -1024 to 1048 PU, ET-1, -252 to 249 PU). The
      variability between these responses was independent of average flux values for
      both ACh and ET-1. There was a significant correlation between responses measured
      in the same site, in the same individual on two different days by the same
      observer (ACh, r = 0.94, P < 0.0001; ET-1, r = 0.90, P < 0.0006), and between
      responses measured by two different observers (ACh, r = 0.94, P < 0.0001; ET-1, r
      = 0.91, P < 0.0003). CONCLUSION: We have shown that interday and intraobserver
      responses to intradermal injections of ET-1 and ACh, assessed using the DIT in
      combination with an LDI scanner, exhibited good reproducibility and may be a
      useful tool for studying the skin microcirculation in vivo.

PMID- 15842549
TI  - Spironolactone reduces brachial pulse wave velocity and PIIINP levels in
      hypertensive diabetic patients.
AB  - AIMS: To assess whether spironolactone has beneficial effects on blood pressure
      (BP), N-terminal propeptide of type III procollagen (PIIINP) and pulse wave
      velocity (PWV) in hypertensive, type II diabetics. METHODS: Ten patients with
      type II diabetes and hypertension were enrolled in a randomized, double-blind
      crossover study comparing 4 months' treatment with spironolactone and placebo
      with a 4-week washout phase. BP, PIIINP and carotid-radial PWV were measured at
      the end of each treatment phase. RESULTS: Compared with placebo, spironolactone
      reduced systolic BP by 15.6 +/- 46.1 mmHg (P = 0.005, 95% CI 2.7-28.5 mmHg),
      PIIINP by 0.6 +/- 0.3 microg l(-1) (P = 0.04, 95% CI 0.02-1.1 microg l(-1)) and
      PWV by 0.6 +/- 0.2 m s(-1) (P = 0.008, 95% CI 0.18-1.02 m s(-1)). CONCLUSIONS:
      Spironolactone is effective at reducing systolic BP and brachial artery stiffness
      as indicated by PWV. It also reduces PIIINP in type II diabetic patients with
      hypertension.

PMID- 15842550
TI  - Ventilatory responses of healthy subjects to intravenous combinations of morphine
      and oxycodone under imposed hypercapnic and hypoxaemic conditions.
AB  - AIMS: Previous isobolographic analysis revealed that coadministration of morphine
      and oxycodone produces synergistic antinociception in laboratory rodents. As both
      opioids can produce ventilatory depression, this study was designed to determine
      whether their ventilatory effects were synergistic when coadministered to healthy
      human subjects. METHODS: A placebo-controlled, randomized, crossover study was
      performed in 12 male volunteers. Ventilatory responses to hypoxaemia and
      hypercapnia were determined from 1-h intravenous infusions of saline ('placebo'),
      15 mg morphine sulphate (M), 15 mg oxycodone hydrochloride (O), and their
      combination in the dose ratios of 1:2, 1:1, 2:1. Drug and metabolite
      concentrations in serial peripheral venous blood samples were measured by high
      performance liquid chromatography-MS/MS. RESULTS: 'Placebo' treatment was without
      significant ventilatory effects. There were no systematic differences between
      active drug treatments on either the slopes or intercepts of the hypoxaemic and
      hypercapnia ventilation responses. During drug treatment, the mean minute
      ventilation at PetCO(2) = 55 mmHg (V(E55)) decreased to 74% of the subjects'
      before treatment values (95% confidence interval 62, 87), 68% (57, 80), 69% (59,
      79), 68% (63, 73), and 61% (52, 69) for M15, M10/O5, M7.5/O7.5, M5/O10 and O15,
      respectively. Recovery was more prolonged with increasing oxycodone doses,
      corresponding to its greater potency and lower clearance compared with morphine.
      CONCLUSIONS: Although adverse ventilatory effects of these drugs were found as
      expected, no unexpected or disproportionate effects of any of the morphine and
      oxycodone treatments were found that might impede their use in combination for
      pain management.

PMID- 15842551
TI  - Influence of activated charcoal on the pharmacokinetics of moxifloxacin following
      intravenous and oral administration of a 400 mg single dose to healthy males.
AB  - AIMS: To evaluate the extent to which enterohepatic recycling circulation
      contributes to moxifloxacin bioavailability in healthy, males by administration
      of activated charcoal and to evaluate the efficacy of activated charcoal
      administration in decreasing systemic concentrations of moxifloxacin in the event
      of overdose. METHODS: Nine healthy males, mean age 34 years (range 23-45 years)
      participated in a single centre, randomized, nonplacebo-controlled, three way
      crossover study. The pharmacokinetics of moxifloxacin in plasma and urine were
      determined for up to 96 h following a 400 mg single dose randomly administered on
      three separate occasions with a minimum washout phase of 1 week. Treatment A was
      400 mg moxifloxacin IV as a 1 h infusion, treatment B was 400 mg moxifloxacin IV
      as a 1 h infusion with oral activated charcoal (5 g directly before the start of
      the infusion, 5 g immediately after the end of the infusion, and 10 g at 2, 4 and
      8 h after the start of the infusion), treatment C was 400 mg oral moxifloxacin
      with activated charcoal (10 g 15 min before and at 2, 4 and 8 h after drug
      administration). The subjects underwent a series of clinical and laboratory
      tests. RESULTS: Single 400 mg doses of moxifloxacin (PO and/or IV) were safe and
      well tolerated. The bioavailability of moxifloxacin was significantly decreased
      when given with charcoal (AUC = 35.5 (IV reference) vs 5.40 (PO) vs 28.5 (IV) mg
      l(-1) h). Concurrently peak concentrations were lowered C(max) = 3.38 (IV
      reference) vs 0.62(PO) vs 2.97 (IV) mg l(-1)) by approximately 85% (P < 0.05)
      following oral administration and by 20% after IV treatment (P < 0.05).
      Bioavailability amounted to 15.4% (95% confidence interval 9.6, 25.0%) for
      treatment B while it was 80.4% (95% confidence interval 76.3.6, 84.6%) for
      treatment C. Terminal half-lives were not affected. The kinetics of urinary
      excretion corroborated these findings. CONCLUSIONS: The results of this study
      show that moxifloxacin undergoes pronounced enteric recycling after systemic
      uptake. In addition, these findings confirm that activated charcoal may be useful
      in treating moxifloxacin overdose by preventing its absorption.

PMID- 15842552
TI  - Determination of the bioavailability of gentamicin to the lungs following
      inhalation from two jet nebulizers.
AB  - AIMS: To determine the bioavailability of gentamicin to the lung following
      inhalation from two jet nebulizers. METHODS: Serial urine samples were obtained
      from 10 volunteers after a 80 mg dose given orally, nebulized from a Pari LC +
      (PARI) and MicroNeb III (MN) devices, or after a 40 mg intravenous dose. In vitro
      aerodynamic characteristics of the nebulized doses were also determined. RESULTS:
      The mean (SD) absolute gentamicin lung bioavailalibility following delivery by
      PARI and MN devices was 1.4 (0.4) and 1.7 (0.5) %. The mass median aerodynamic
      diameter (MMAD) of the drug particles from the PARI and MN systems was 8.6 (0.6)
      and 6.7 (0.5) microm and the corresponding fine particle doses (FPD) were 10.2
      (2.8) and 11.7 (1.5) mg. CONCLUSIONS: The MMAD and FPD data reflect the poor lung
      deposition of gentamicin identified by urinary excretion.

PMID- 15842553
TI  - Influence of acute upper respiratory tract infection on the absorption of inhaled
      insulin using the AERx insulin Diabetes Management System.
AB  - AIMS: To assess the effects due to an uncomplicated acute upper respiratory tract
      infection (URTI) on the pharmacokinetics and glucose response of insulin when
      delivered by oral pulmonary absorption. METHODS: Normally healthy adult men (n =
      11) and women (n = 9) received a single dose of inhaled human insulin, equivalent
      to approximately 6 IU subcutaneous, using the AERx insulin Diabetes Management
      System (iDMS), during and following recovery from an URTI. The first dose was
      administered with ongoing symptoms of < 3 days' duration, the second dose
      following recovery, and within 3 weeks of the first. Blood sampling for
      determination of insulin pharmacokinetics (serum AUC(0-6 h), AUC(0-8),
      C(max),t(max), t(1/2), MRT) and glucose response (plasma AOC(0-6 h)) was
      performed from 15 min predose to 6 h postdose. RESULTS: Insulin pharmacokinetics
      were not different for subjects during and following recovery from URTI [e.g.
      URTI: no URTI ratio in serum AUC(0-6 h) = 0.92 (95% confidence interval 0.81,
      1.05)]; this was reflected by a similar glucose response. Inhaled insulin
      delivered by AERx iDMS was well tolerated by all subjects; no significant changes
      were observed in pulmonary function tests. No safety concerns arising from the
      mode of insulin administration were raised by either dose. CONCLUSIONS: The
      results suggest that insulin can be administered via AERx iDMS to nondiabetic
      subjects experiencing a URTI without any statistically significant changes in
      insulin pharmacokinetics or pharmacodynamics, and that the necessity for dose
      adjustments will not differ from subjects with an acute URTI who are receiving
      subcutaneous insulin.

PMID- 15842554
TI  - Chlorpropamide 2-hydroxylation is catalysed by CYP2C9 and CYP2C19 in vitro:
      chlorpropamide disposition is influenced by CYP2C9, but not by CYP2C19 genetic
      polymorphism.
AB  - AIMS: We evaluated the involvement of cytochrome P450 (CYP) isoforms 2C9 and 2C19
      in chlorpropamide 2-hydroxylation in vitro and in chlorpropamide disposition in
      vivo. METHODS: To identify CYP isoforms(s) that catalyse 2-hydroxylation of
      chlorpropamide, the incubation studies were conducted using human liver
      microsomes and recombinant CYP isoforms. To evaluate whether genetic
      polymorphisms of CYP2C9 and/or CYP2C19 influence the disposition of
      chlorpropamide, a single oral dose of 250 mg chlorpropamide was administered to
      21 healthy subjects pregenotyped for CYP2C9 and CYP2C19. RESULTS: In human liver
      microsomal incubation studies, the formation of 2-hydroxychlorpropamide (2-OH
      chlorpropamide), a major chlorpropamide metabolite in human, has been best
      described by a one-enzyme model with estimated K(m) and V(max) of 121.7 +/- 19.9
      microm and 16.1 +/- 5.0 pmol min(-1) mg(-1) protein, respectively. In incubation
      studies using human recombinant CYP isoforms, however, 2-OH-chlorpropamide was
      formed by both CYP2C9 and CYP2C19 with similar intrinsic clearances (CYP2C9 vs.
      CYP2C19: 0.26 vs. 0.22 microl min(-1) nmol(-1) protein). Formation of 2-OH
      chlorpropamide in human liver microsomes was significantly inhibited by
      sulfaphenazole, but not by S-mephenytoin, ketoconazole, quinidine, or
      furafylline. In in vivo clinical trials, eight subjects with the CYP2C9*1/*3
      genotype exhibited significantly lower nonrenal clearance [*1/*3 vs.*1/*1: 1.8 +/
      0.2 vs. 2.4 +/- 0.1 ml h(-1) kg(-1), P < 0.05; 95% confidence interval (CI) on
      the difference 0.2, 1.0] and higher metabolic ratios (of chlorpropamide/2-OH
      chlorpropamide in urine: *1/*3 vs.*1/*1: 1.01 +/- 0.19 vs. 0.56 +/- 0.08, P <
      0.05; 95% CI on the difference - 0.9, - 0.1) than did 13 subjects with
      CYP2C9*1/*1 genotype. In contrast, no differences in chlorpropamide
      pharmacokinetics were observed for subjects with the CYP2C19 extensive
      metabolizer vs. poor metabolizer genotypes. CONCLUSIONS: These results suggest
      that chlorpropamide disposition is principally determined by CYP2C9 activity in
      vivo, although both CYP2C9 and CYP2C19 have a catalysing activity of
      chlorpropamide 2-hydroxylation pathway.

PMID- 15842555
TI  - Persistence and determinants of statin therapy among middle-aged patients for
      primary and secondary prevention.
AB  - AIMS: Statins have been shown to significantly reduce morbidity and mortality in
      patients with coronary artery disease (CAD), and also in patients with
      dyslipidaemia when statins are taken regularly. Middle-aged patients have the
      highest level of forecasting benefit and little is known about persistence rate
      of these therapies in a real-life setting. The objective was to evaluate the
      persistence rate of middle-aged patients initiating a statin therapy and its
      relation with several determinants for primary and secondary prevention. METHODS:
      A cohort was reconstructed using the RAMQ databases. All patients aged 50-64
      years-old who received at least one statin prescription between 1 January, 1998
      and 31 December, 2000 for a new intention of treatment for dyslipidaemia were
      included in the cohort and followed up until 30 June, 2001. The date of the first
      prescription of statin was defined as the index date. There were 4316 patients in
      the secondary prevention (CAD diagnosis) and 13,642 patients in primary
      prevention cohort. The cumulative persistence rate was estimated using Kaplan
      Meier, and Cox regression models were used to estimate the hazard ratio of
      ceasing statins. RESULTS: We found that persistence with statins had fallen to
      71% after 6 months of treatment, and had declined to 45% after 3 years in the
      secondary prevention cohort; the corresponding figures were 65% and 35% in the
      primary prevention cohort. Our results suggest that patients with dyslipidaemia
      in primary prevention compared with those in secondary prevention (HR: 1.18; 1.11
      1.25) are less likely to be persistent. Patients with other cardiovascular risk
      factors such as age (HR: 0.99; 0.98-0.99), diabetes (HR: 0.84; 0.79-0.90),
      hypertension (HR: 0.76; 0.72-0.80) were most likely to be persistent with
      statins. We observed lower persistence in patients who have used the greatest
      number of pharmacies and prescribing physicians. CONCLUSION: This analysis
      indicates that barriers to persistence occur early in the therapeutic course.
      Overall persistence with statins is low, and particularly among patients with few
      other cardiovascular risk factors.

PMID- 15842556
TI  - Khat chewing is a risk factor for acute myocardial infarction: a case-control
      study.
AB  - AIM: Khat chewing is a common habit in Yemen and east African countries. Millions
      of people chew khat leaves daily for its euphoric and energetic effects and to
      increase alertness. Cathinone, the main active substance in fresh khat leaves,
      has sympathomimetic effects which increase heart rate and blood pressure. The aim
      was to examine the hypothesis that khat chewing is a risk factor for acute
      myocardial infarction (AMI) using a hospital-based matched case-control study.
      METHOD: Between 1997 and 1999, we selected 100 patients admitted to the Al-Thawra
      teaching hospital Sana'a ICU, Yemen with acute myocardial infarction. 100 control
      subjects, matched to cases for sex and age, were recruited from the outpatients
      clinics of the same hospital. A questionnaire was completed for case and control
      groups covering personal history of khat chewing, smoking, hypertension, diabetes
      and any family history of myocardial infarction. A blood sample was collected for
      performing lipid profiles. Cases and controls were compared by analysis conducted
      using conditional logistic regression which corrected for baseline imbalances
      leading to less biased estimations of odds ratio (OR). The risk associated with
      each classical factor and khat chewing habits was then investigated. OR values
      greater than 2.5 indicated a significant risk factor. RESULTS: Khat chewing was
      significantly higher among the AMI case group than control group (OR = 5.0, 95%
      CI 1.9-13.1). A dose-response relationship was observed, the heavy khat chewers
      having a 39-fold increased risk of AMI. CONCLUSION: This study indicates that
      khat chewing is associated with AMI and is an independent dose-related risk
      factor for the development of myocardial infarction.

PMID- 15842557
TI  - Is INR between 2.0 and 3.0 the optimal level for Chinese patients on warfarin
      therapy for moderate-intensity anticoagulation?
AB  - AIM: To examine the optimal range of International Normalized Ratio (INR) for
      Chinese patients receiving warfarin for moderate-intensity anticoagulation.
      METHODS: This was a retrospective cohort study conducted at the ambulatory
      setting of a 1400-bed public teaching hospital in Hong Kong. The INR measurements
      and occurrence of serious or life-threatening haemorrhagic and thromboembolic
      events among patients newly started on warfarin from 1 January 1999 to 30 June
      2001 for indications with target INR 2-3 were analysed. The INR-specific
      incidence of bleeding and thromboembolism were calculated. RESULTS: A total of
      491 patients were included, contributing to 453 patient-years of observation
      period. Forty-seven of the 491 patients experienced 25 haemorrhagic events (5.5
      per 100 patient-years) and 27 thromboembolic events (6.0 per 100 patient-years).
      The percentage of patient-time spent within therapeutic INR range (2-3), INR <2
      and INR >3 were 50, 44 and 6%, respectively. The incidence of either haemorrhagic
      or thromboembolic events was lowest (< or =4 events per 100 patient-years) at INR
      values between 1.8 and 2.4. CONCLUSIONS: An INR of 1.8-2.4 appeared to be
      associated with the lowest incidence rate of major bleeding or thromboembolic
      events in a cohort of Hong Kong Chinese patients receiving warfarin therapy for
      moderate-intensity anticoagulation.

PMID- 15842558
TI  - Ocular side-effects of tolterodine and oxybutynin, a single-blind prospective
      randomized trial.
AB  - AIM: To evaluate the effects of tolterodine and oxybutynin on visual
      accommodation, pupillary diameter, intraocular pressure and tear secretion in
      women with overactive bladder. METHODS: One hundred and four eyes from 52
      consecutive female patients (age range: 22-60 years) with a urodynamic diagnosis
      of overactive bladder were prospectively investigated. Patients with a history of
      ocular disease or surgery were excluded. The subjects were randomly assigned to
      one of two groups: Group I received 2 mg tolterodine bid and Group II received 5
      mg oxybutynin tid. All patients were evaluated at baseline (day 0) and after 1
      month of treatment (day 28) by an ophthalmologist who was blinded to the
      medication. At each time point, a complete ophthalmic examination was performed
      and accommodation amplitude (AA), and pupillary diameter (PD) in dim and bright
      light were recorded. As well, tear secretion was assessed based on tear film
      break-up time and Schirmer I-test results. Statistical comparisons were made
      using the chi-square test, Student's t-test and Mann-Whitney U-test, as
      appropriate. RESULTS: Twenty-eight patients (56 eyes) received tolterodine and 24
      patients (48 eyes) received oxybutynin. The mean ages of the two groups were
      similar (P = 0.523). After 4 weeks of treatment, AA was significantly lower in
      the oxybutynin treated group (P = 0.003, 95% CI 0.15, 0.62) whereas there was no
      significant change in AA in the tolterodine treated group (P = 0.155, 95% CI 
      0.042, 0.86). At day 28, PD in dim light was significantly larger in the
      tolterodine treated group (P = 0.031, 95% CI -0.82, -0.06), whereas no
      significant change in PD in dim light was noted in the oxybutynin treated group
      (P = 0.330, 95% CI -0.38, 0.18). Neither group showed a significant change in PD
      in bright light values on day 28 (P > 0.05 for both). In each group, the
      differences from day 0 to day 28 for intraocular pressure, and Schirmer-I results
      were insignificant (P > 0.05 for all). Both groups had significantly shorter tear
      film break-up time after 1 month of therapy (P = 0.014 (95% CI 0.47, 3.81) and P
      = 0.02 (95% CI 1.14, 4.61) for the tolterodine and oxybutynin treated groups,
      respectively). CONCLUSION: Four weeks of standard-dose oxybutynin treatment in
      women with overactive bladder decreases AA significantly, whereas the same
      duration of standard-dose tolterodine does not have this effect. However,
      tolterodine seemed to affect PD in dim light. One month of treatment with either
      of these anticholinergic drugs shortens tear film break-up time significantly.
      Concerning ocular side-effects, tolterodine seems to offer an advantage over
      oxybutynin because it does not affect AA, however, the shorter tear film break-up
      time with both agents suggests potential problems for patients who already have
      dry eye.

PMID- 15842559
TI  - Pharmacokinetic interaction on valproic acid and recurrence of epileptic seizures
      during chemotherapy in an epileptic patient.
AB  - AIMS: To report a pharmacokinetic interaction between valproic acid (VPA) and
      anticancer agents observed in an epileptic patient. METHODS: A 34-year old male
      epileptic patient receiving VPA underwent cisplatin-based chemotherapy for the
      treatment of a testicular tumour. The first chemotherapeutic cycle decreased the
      serum VPA concentration and caused severe generalized tonic-clonic seizures.
      Thus, thereafter, the serum VPA concentration was monitored along with the
      chemotherapy. RESULTS: In a patient receiving VPA daily, severe seizures were
      observed 7 weeks after the first chemotherapeutic cycle, at which the serum VPA
      concentration was found to be reduced by approximately 50% of the initial level
      (90-100 microg ml(-1)). The following cycles (six cycles over a 7-month period)
      also caused seizures in association with decreased serum VPA concentrations. In
      contrast, the serum concentration of phenytoin, which was given daily after the
      second chemotherapeutic cycle, remained at a therapeutic concentration (10-20
      microg ml(-1)). After the completion of chemotherapy, the serum concentration of
      a tumour marker, hCGbeta, decreased to 1.2 ng ml(-1) from more than 120 ng ml(-1)
      prior to the chemotherapy in this patient. CONCLUSIONS: Careful monitoring of VPA
      concentrations are necessary during cisplatin-based chemotherapy because
      anticancer agents can reduce the serum concentration and antiepileptic activity
      of VPA.

PMID- 15842560
TI  - Lack of effect of moderate hepatic impairment on the pharmacokinetics of oral
      oseltamivir and its metabolite oseltamivir carboxylate.
AB  - AIMS: To compare the pharmacokinetics of oseltamivir and oseltamivir carboxylate
      in hepatically impaired patients and healthy subjects. METHODS: Hepatically
      impaired patients (n = 11) and healthy subjects (n = 11) were individually paired
      on the basis of gender, age (+/-10 years) and body weight (+/-20%) and
      administered a single dose of oseltamivir (75 mg). RESULTS: Oseltamivir and
      oseltamivir carboxylate C(max) were < or =6% and < or =19% lower, and their
      AUC(0,infinity) 33% higher and < or =19% lower, respectively, in hepatically
      impaired patients compared with healthy subjects. These changes are within the
      safety limits for the drug. CONCLUSIONS: The metabolism of oseltamivir is not
      compromised [corrected] in hepatically impaired patients. No dose adjustment is
      required in these patients when receiving oseltamivir.

PMID- 15842561
TI  - Fexofenadine pharmacokinetics are associated with a polymorphism of the SLCO1B1
      gene (encoding OATP1B1).

PMID- 15842563
TI  - Statins, lack of energy and ubiquinone.

PMID- 15842564
TI  - Brugada-like ECG abnormalities during thioridazine overdose.

PMID- 15842567
TI  - Expert witness malfeasance: how should specialty societies respond?
AB  - There is little doubt that severe distortions are present in the legal
      adjudication of professional medical liability. The medical expert witness plays
      an important, often crucial, role in the medical liability cases. The expert
      assesses medical information, interprets and explains medical uncertainty,
      medical research, and customary practice for a nonscientific jury, and offers an
      expert level opinion as to whether the standard of medical care was met. When
      expert witnesses not merely disagree, but misrepresent data, misrepresent their
      background credentials and expertise, and offer egregiously false testimony, the
      legal process is violated and verdicts may be distorted. Many medical and
      surgical professional organizations, including the American Medical Association,
      have adopted programs that provide guidelines for members who serve as medical
      expert witnesses in professional liability cases. The American Association of
      Neurological Surgeons (AANS) was the first to develop a program to deal with
      irresponsible expert witness testimony. That program involves a published code of
      conduct, which outlines the expectations of society regarding expert witness
      testimony, and potential consequences for noncompliance. To date, the AANS
      program has withstood court challenge, in fact, has received judicial praise.
      Other medical societies, including the American College of Gastroenterology
      (ACG), have reviewed efforts by others and are considering developing their own
      programs.

PMID- 15842568
TI  - Sedation for gastrointestinal endoscopy: new practices, new economics.

PMID- 15842570
TI  - Fundoplication and the risk of esophageal cancer in gastroesophageal reflux
      disease: a Veterans Affairs cohort study.
AB  - BACKGROUND AND AIMS: It has been proposed that fundoplication can reduce the risk
      of esophageal cancer in patients with gastroesophageal reflux disease (GERD). In
      this cohort study, we assessed the effect of fundoplication on the incidence of
      esophageal cancer. METHODS: We identified all Veterans Affairs (VA) patients with
      GERD who had fundoplication between 1986 and 1990 and matched (1-2) to controls
      with GERD and no fundoplication and to controls with no GERD. We calculated
      incidence rates for esophageal cancer through October 2002 and examined the
      effect of fundoplication on the risk of esophageal cancer using Kaplan-Meier
      survival analysis and Cox proportional hazard analysis. We calculated and
      adjusted for the propensity score for receiving fundoplication. RESULTS: We
      identified 946 patients who had fundoplication, 1,892 patients who had GERD
      without fundoplication, and 5,676 patients with no GERD. The mean age was 55 yr
      and 97.5% were men in all three groups. During a follow-up of 11,156 patient
      years (PY), there were eight cases of esophageal cancer (72/100,000) in the
      fundoplication group. During a follow-up of 20,115 PY, there were eight cases of
      esophageal cancer (40/100,000) in the GERD without fundoplication group. During a
      follow-up of 59,439 PY, no patients in the group with no GERD developed
      esophageal cancer. The Kaplan-Meier analysis showed no significant difference in
      cumulative esophageal cancer rates between the fundoplication group and the GERD
      no-fundoplication group. The adjusted hazard ratio of esophageal cancer with
      fundoplication was 1.88 (95% CI: 0.70-5.03). CONCLUSIONS: GERD is a risk factor
      for esophageal cancer, but there is insufficient evidence that fundoplication
      reduces that risk.

PMID- 15842571
TI  - Does fundoplication change the risk of esophageal cancer in the setting of GERD?
AB  - The effect of a surgical antireflux procedure on the risk of cancer in those with
      GERD and Barrett's esophagus is unclear. Although some authorities have suggested
      that a surgical antireflux procedure might be superior to medical management for
      the prevention of cancer, the cumulative data do not demonstrate that those
      patients undergoing surgery have any decrement in cancer risk compared to those
      who receive medication. Most data available to assess the effect of surgery on
      cancer risk come from case series. These data are of very limited utility,
      because of differences in the baseline composition of groups undergoing medical
      and surgical therapy. Until more data are available, patients should not be
      advised to undergo surgical fundoplication as an antineoplastic measure.

PMID- 15842572
TI  - Prediction of malignant potential in reflux disease: are cytokine polymorphisms
      important?
AB  - OBJECTIVES: Esophageal reflux is common in the Western world and can lead to a
      number of diseases, such as esophagitis, Barrett's esophagus, and adenocarcinoma.
      Barrett's predisposes to adenocarcinoma and endoscopic surveillance may lead to
      earlier detection of adenocarcinoma. However, clinical methods only identify one
      patient in 15 with Barrett's esophagus. The aim of this study was to find factors
      that may help identify patients with Barrett's earlier. METHODS: Blood samples
      and detailed histories were taken from 456 patients with gastroesophageal reflux
      who were recruited into three study groups: esophagitis, Barrett's esophagus
      without dysplasia, and Barrett's with dysplasia or adenocarcinoma. PCR was used
      to determine the frequency of five functional cytokine polymorphisms: interleukin
      1 receptor antagonist position +2018 (IL-1 Ra +2018), interleukin-1 beta position
      -511 (IL-1 beta-511), tumor necrosis factor-alpha position -238 (TNF-alpha-238),
      interleukin-10 position +1082 (IL-10 +1082), and interleukin-4 receptor position 
      1902 (IL-4R -1902). RESULTS: IL-1 Ra +2018 genotype 2/2 was associated with
      Barrett's more commonly than esophagitis (OR-3.7, p= 0.0345). The IL-10 +1082
      genotype 2/2 was more strongly associated with Barrett's and adenocarcinoma than
      esophagitis (OR-1.76, p= 0.056 and OR 1.96, p= 0.025, respectively). There were
      no differences for the IL-1 beta-511, IL-4R -1902, and TNF-alpha-238
      polymorphisms. CONCLUSIONS: Cytokine polymorphisms are more commonly found in
      patients with Barrett's or adenocarcinoma than those with esophagitis. Together
      with demographic data, this may help identify those patients with Barrett's who
      would benefit from surveillance.

PMID- 15842573
TI  - Prediction of malignant potential in reflux disease.
AB  - There is interest in noninvasive means of identifying reflux patients at
      increased risk of developing Barrett's esophagus and adenocarcinoma. In this
      issue, Gough et al. studied the prevalence of polymorphisms of cytokine genes in
      patients with uncomplicated esophagitis versus Barrett's/esophageal
      adenocarcinoma. They reported a difference between the groups with respect to the
      interleukin-1 receptor antagonist and interleukin-10 genes. However, the number
      of comparisons carried out mean that the association is not statistically
      significant and further studies will be required to confirm/refute the
      association. The genetic markers reported would unfortunately be of little value
      in predicting individual risk of esophageal adenocarcinoma as they are weak
      predictors and relatively rare within the esophagitis population. The findings of
      this study demonstrate the general principle that polymorphisms of individual
      genes are of limited value in identifying patients at risk of sporadic-types of
      cancer such as most cases of esophageal adenocarcinoma.

PMID- 15842574
TI  - Acid and duodenogastroesophageal reflux after esophagectomy with gastric tube
      reconstruction.
AB  - OBJECTIVE: Patients who undergo esophagectomy with gastric tube reconstruction
      incur increased risk for acid reflux and duodenogastroesophageal reflux. Few
      postesophagectomy studies of gastroesophageal reflux disease have included
      simultaneous 24-h pH and bilirubin monitoring. The aim of this study is to
      evaluate acid reflux and duodenogastroesophageal reflux after esophagectomy with
      gastric tube reconstruction. METHODS: Reflux symptom evaluation, endoscopy, and
      simultaneous 24-h pH and bilirubin monitoring in the cervical esophagus were
      performed in 25 patients who underwent Ivor Lewis esophagectomy, intrathoracic
      esophagogastrostomy, and digital dilation of the pyloric ring as treatment for
      esophageal cancer. RESULTS: Reflux symptoms were severe, mild, and absent in 2,
      7, and 16 patients, respectively. Reflux esophagitis and Barrett's esophagus was
      observed in 11 and 1 patients, respectively. Elevated acid reflux occurred in 7
      patients (28%). Elevated duodenogastroesophageal reflux was recorded in 11
      patients (44%). Reflux profile analysis identified three patterns: 4 subjects
      (16%) with both elevated acid reflux and duodenogastroesophageal reflux; 3 (12%)
      with only elevated acid reflux; and 7 (28%) with only elevated
      duodenogastroesophageal reflux. Of 7 patients with only elevated
      duodenogastroesophageal reflux, 4 developed reflux esophagitis. Although reflux
      symptoms did not correlate with endoscopic esophagitis, a significant correlation
      was observed between endoscopic esophagitis and acid reflux and/or
      duodenogastroesophageal reflux. CONCLUSIONS: Reflux symptoms represented a poor
      indication of esophagitis in patients with esophagectomy and gastric tube
      reconstruction. Simultaneous 24-h pH and bilirubin monitoring can help in
      identifying patients at high risk for reflux esophagitis, as well as indicating
      the cause of esophagitis.

PMID- 15842575
TI  - Improvements with esomeprazole in patients with upper gastrointestinal symptoms
      taking non-steroidal antiinflammatory drugs, including selective COX-2
      inhibitors.
AB  - OBJECTIVES: Upper gastrointestinal (GI) symptoms are common in patients using non
      steroidal antiinflammatory drugs (NSAIDs) including selective cyclooxygenase
      (COX)-2 inhibitors and may be acid related. We therefore assessed esomeprazole
      treatment for upper GI symptoms in these patients. METHODS: A total of 794 and
      848 continuous NSAID users, free of gastroduodenal ulcers, erosive esophagitis,
      and Helicobacter pylori, were enrolled into two identical, multinational,
      multicenter double-blind studies (NASA1, SPACE1). Moreover, 608 and 556 patients
      were randomized to receive 4 wk esomeprazole 20 mg, or 40 mg, or placebo once
      daily. The primary variable was the patient-reported change in the upper GI
      symptom (pain, discomfort, or burning in the upper abdomen) score on a 7-graded
      severity scale (0-6) from the 7 days prior to treatment to the last 7 days in the
      study. RESULTS: Esomeprazole was associated with highly significant symptom
      improvement compared to placebo. Symptom improvements were 2.30 mean [SD 1.63] on
      esomeprazole 20 mg and 2.03 [1.56] on esomeprazole 40 mg versus 1.64 [1.57] on
      placebo in NASA1 and 2.17 [1.34] and 2.12 [1.48]versus 1.56 [1.26], respectively,
      in SPACE1 (all placebo comparisons at least p < 0.001). Esomeprazole-improved
      symptoms in patients taking selective COX-2 inhibitors, with changes of 2.21
      [1.46] and 1.92 [1.38]versus 1.64 [1.46] in NASA1 and 2.20 [1.26] and 2.24
      [1.62]versus 1.58 [1.37] in SPACE1 (all placebo comparisons at least p < 0.05),
      as well as those on non-selective NSAIDs. Esomeprazole was well tolerated and
      associated with significant improvements in HRQL. CONCLUSION: Esomeprazole 20 mg
      and 40 mg improve upper GI symptoms associated with continuous, daily NSAID
      therapy, including selective COX-2 inhibitors.

PMID- 15842576
TI  - The effect of eradicating helicobacter pylori on the development of gastric
      cancer in patients with peptic ulcer disease.
AB  - OBJECTIVES: Infection with Helicobacter pylori is a risk factor for the
      development of gastric cancer. However, it is not known whether eradication
      therapy can prevent the development of gastric cancer in persons in whom the
      cancer is not yet established. In the present study, we investigated whether the
      eradication of H. pylori in patients with peptic ulcer disease reduces the
      likelihood of their developing gastric cancer. METHODS: Prospective
      posteradication evaluations were conducted in 1,342 consecutive patients (1,191
      men and 151 women; mean age: 50 yr) with peptic ulcer diseases who had received
      H. pylori eradication therapy. After confirmation of eradication, endoscopy and a
      urea breath test were performed yearly. RESULTS: A total of 1,120 patients
      completed more than 1-yr follow-up and were followed for up to 8.6 yr (a mean of
      3.4 yr). Gastric cancer developed in 8 of 944 patients cured of infection and 4
      of 176 who had persistent infection (p= 0.04; log-rank test). All the gastric
      cancer developed in patients with gastric ulcer, but none in patients with
      duodenal ulcer (p= 0.005; Fisher's exact test). In patients with gastric ulcer,
      persistent infection was identified as a significant factor for the risk of
      developing gastric cancer (hazard ratio: 3.35; 95% confidence interval: 1.00
      11.22; p= 0.04; Cox's proportional-hazards model). CONCLUSION: H. pylori
      eradication may reduce their risk of developing gastric cancer in patients with
      gastric ulcer. Large-scale studies in additional populations of this important
      international public-health issue are warranted.

PMID- 15842577
TI  - Valdecoxib is associated with improved dyspepsia-related health compared with
      nonspecific NSAIDs in patients with osteoarthritis or rheumatoid arthritis.
AB  - OBJECTIVES: Dyspepsia and related gastrointestinal (GI) symptoms are commonly
      reported by patients taking nonspecific nonsteroidal anti-inflammatory drugs
      (NSAIDs) and significantly impact treatment effectiveness, cost, and quality of
      life. This study sought to evaluate dyspepsia-related health in osteoarthritis
      (OA) and rheumatoid arthritis (RA) patients taking valdecoxib compared with
      patients taking nonspecific NSAIDs. METHODS: Analysis of two separate, double
      blind, placebo-controlled studies: one in RA patients randomized to placebo,
      valdecoxib (10 and 20 mg once daily [o.d.]) and naproxen (500 mg twice daily
      [b.i.d.]); one in OA patients randomized to placebo, valdecoxib (10 and 20 mg
      o.d.), diclofenac (75 mg b.i.d.), or ibuprofen (800 mg three times daily
      [t.i.d.]). Study population comprised patients with RA in flare or clinically
      documented OA who required chronic symptomatic treatment with NSAIDs/analgesics.
      Dyspepsia-related health was evaluated at baseline and weeks 2, 6, and 12 (or
      early termination) using the validated Severity of Dyspepsia Assessment (SODA)
      questionnaire. This patient self-report tool consists of scales for evaluating
      dyspepsia pain intensity, nonpain symptoms, and satisfaction. Analysis was based
      on the intent-to-treat population with the last observation carried forward.
      RESULTS: Valdecoxib was significantly better at endpoint than standard doses of
      naproxen, diclofenac, and ibuprofen for pain intensity scores (p < 0.05), and
      provided significantly improved nonpain symptom and satisfaction scores compared
      with naproxen for patients with RA (p < 0.05). For RA patients, the difference
      between valdecoxib and naproxen pain intensity scores were clinically meaningful;
      at all the time points, significantly fewer patients receiving valdecoxib
      reported severe dyspepsia pain intensity increases (>/=10 points) than those
      receiving naproxen. At 12 wk, fewer patients receiving valdecoxib reported severe
      dyspepsia pain intensity increases versus those receiving ibuprofen and
      diclofenac. CONCLUSIONS: The GI tolerability of valdecoxib is superior to that of
      nonspecific NSAIDs, and therefore can potentially have a favorable impact on
      patient quality of life.

PMID- 15842578
TI  - The detection of bile duct stones in suspected biliary pancreatitis: comparison
      of MRCP, ERCP, and intraductal US.
AB  - OBJECTIVES: Early ERCP and endoscopic sphincterotomy for stone extraction can
      benefit the prognosis in patients with severe biliary pancreatitis, but are
      associated with complications. The ability to identify choledocholithiasis by
      noninvasive means in biliary pancreatitis is limited. The aim of this study was
      evaluation of the ability of MRCP to detect choledocholithiasis in patients with
      acute biliary pancreatitis. In addition, we investigated whether intraductal US
      (IDUS) could help manage these patients. METHODS: Thirty-two patients with
      suspected biliary pancreatitis were studied prospectively. MRCP was performed
      immediately before ERCP by separate blinded examiners within 24 h of admission.
      Wire-guided IDUS was performed during ERCP within 72 h of admission, regardless
      of the results of MRCP. Using endoscopic extraction of a stone as the reference
      standard, the diagnostic yield of MRCP was compared with transabdominal US, CT,
      ERCP, and IDUS. RESULTS: The sensitivity of US, CT, MRCP, ERCP, and IDUS for
      identifying choledocholithiasis was 20.0%, 40.0%, 80.0%, 90.0%, and 95.0%,
      respectively. The overall agreement between MRCP and ERCP was 90.6% for
      choledocholithiasis (kappa= 0.808, p < 0.01). The sensitivity of MRCP for
      detecting choledocholithiasis decreased with dilated bile ducts (bile duct
      diameter > 10 mm, 72.7% vs 88.9%). The combination of ERCP and IDUS improved
      accuracy in the diagnosis of choledocholithiasis. CONCLUSIONS: MRCP can be used
      to select patients with biliary pancreatitis who require ERCP. IDUS may be
      applied in the management of biliary pancreatitis if ERCP is performed.

PMID- 15842579
TI  - Yield of repeat wireless video capsule endoscopy in patients with obscure
      gastrointestinal bleeding.
AB  - PURPOSE: Capsule endoscopy (CE) has been shown to have a high diagnostic yield in
      patients with obscure gastrointestinal bleeding (OGIB). It is not known if
      repeating CE improves diagnostic yield or changes patient management when the
      initial CE is negative or nondiagnostic. The aims of this study are (1) to
      understand the reasons for repeat CE, (2) to determine the diagnostic yield of
      repeat CE, and (3) to establish if findings on repeat CE resulted in a change in
      patient management. METHODS: Between August 2001 and October 2003, we performed
      391 capsule studies. Of these, 24 were repeat studies in patients with OGIB. We
      retrospectively reviewed the charts of these 24 patients. RESULTS: The reasons
      for repeat CE were: recurrent gastrointestinal bleeding (13), limited
      visualization on first exam due to poor prep or blood (10), complication (1)
      (capsule impaction at cricopharyngeus). Eighteen of 24 (75%) repeat capsule
      studies revealed additional findings (7 arteriovenous malformations, 2
      gastropathy, 2 erosions, 2 masses, 1 ulcer, 2 red spots, 1 linear streak, 1
      erythema). These findings led to changes in patient management in 15 of the 24
      (62.5%) cases. CONCLUSIONS: Indications for repeat CE most commonly include
      recurrent gastrointestinal bleeding and limited visualization on initial study.
      Repeat CE results in a high yield of new findings that lead to changes in patient
      management. Repeat CE should be considered in patients with persistent OGIB when
      the initial study is negative or inconclusive.

PMID- 15842580
TI  - Feasibility and safety of string wireless capsule endoscopy in the diagnosis of
      esophageal varices.
AB  - OBJECTIVE: To assess the feasibility, safety, accuracy, and acceptability of
      "string-capsule endoscopy" in the evaluation of esophageal varices. MATERIAL AND
      METHODS: Strings were attached to the wireless capsule endoscopy device to allow
      its controlled movement up and down the esophagus. Time of recording and
      discomfort associated with the procedure was documented. Patient's preference
      compared to conventional esophago-gastro-duodenoscopy (EGD) was recorded. An
      independent endoscopist blinded to EGD diagnoses assessed the diagnostic accuracy
      of pictures obtained. RESULTS: Thirty patients with clinical liver cirrhosis
      (mean age: 54.4 yr; mean MELD score: 12.5, and mean Child-Pugh score: 6.3) were
      enrolled; 19 for surveillance and 11 for screening purposes. The procedure was
      safe (no strings were disrupted and no capsule was lost). The mean recording time
      was 5.8 min (2.9-8.7), the accuracy 96.7%, and discomfort was minimal. The
      majority (83.3%) of patients preferred string-capsule endoscopy to EGD.
      CONCLUSIONS: String-capsule endoscopy was feasible, safe, accurate, highly
      acceptable, and preferred by cirrhotic patients undergoing screening/surveillance
      of esophageal varices. The technique may prove to be more cost effective than
      conventional EGD.

PMID- 15842581
TI  - One-year intense nutritional counseling results in histological improvement in
      patients with non-alcoholic steatohepatitis: a pilot study.
AB  - BACKGROUND AND AIM: In individuals with biopsy-proven non-alcoholic
      steatohepatitis (NASH), short-term weight loss has been shown to improve
      biochemical abnormalities; however, its effect on liver histology is largely
      unknown. The aim of the article is to determine if dietary intervention is
      effective in improving histological features of steatohepatitis in patients with
      biopsy-proven NASH. METHODS: Twenty-three patients (11M/12F) with BMI >25 kg/m(2)
      and biopsy-proven NASH received standardized nutritional counseling aimed at
      reducing insulin resistance (IR) and weight. Blood tests were checked at baseline
      and every 1-4 months, and liver biopsy was repeated at month 12. IR was assessed
      by the homeostasis model assessment (HOMA). Liver biopsies were scored according
      to modified Brunt criteria for NASH. "Histologic response" was defined as a
      reduction in total NASH score of >/=2 points with at least one point being in the
      non-steatosis component. RESULTS: Sixteen patients (8M/8F) completed 12 months of
      dietary intervention, and 15 underwent repeat liver biopsies. At month 12, mean
      weight decreased from 98.3 to 95.4 kg. Mean waist circumference, visceral fat,
      fasting glucose, IR, triglycerides, AST, ALT, and histologic score were all
      reduced but the difference was not significant. Nine patients had a histologic
      response, six had stable scores, and none had a worsened score. Compared to
      patients with unchanged histologic scores, patients with improved scores had
      significantly greater reduction in weight, waist circumference, AST, ALT,
      steatosis grade, and total NASH score. CONCLUSION: Among patients who
      successfully completed 1 yr of intense dietary intervention, nine of 15 patients
      with NASH displayed histologic improvement. This pilot study suggests that
      dietary intervention can be effective in improving histology in patients with
      biopsy-proven NASH.

PMID- 15842582
TI  - A randomized controlled trial of metformin versus vitamin E or prescriptive diet
      in nonalcoholic fatty liver disease.
AB  - OBJECTIVES: Metformin proved useful in the treatment of nonalcoholic fatty liver
      disease (NAFLD), but its superiority over nutritional treatment and antioxidants
      has never been demonstrated. We aimed to compare the usefulness of metformin
      versus prescriptive diet or vitamin E. METHODS: In an open label, randomized
      trial, nondiabetic NAFLD patients were given metformin (2 g/day; n = 55) for 12
      months. The control cases were given either vitamin E (800 IU/day; n = 28) or
      were treated by a prescriptive, weight-reducing diet (n = 27). Outcome measures
      were liver enzymes, insulin resistance (homeostasis model assessment), parameters
      of the metabolic syndrome, and histology. RESULTS: Aminotransferase levels
      improved in all groups, in association with weight loss. The effects in the
      metformin arm were larger (p < 0.0001), and alanine aminotransferase normalized
      in 56% of cases (odds ratio (OR) versus. controls, 3.11; 95% confidence interval
      (CI), 1.56-6.20; p= 0.0013). In multivariate analysis, metformin treatment was
      associated with higher rates of aminotransferase normalization, after correction
      for age, gender, basal aminotransferases, and change in body mass index (OR,
      5.98; 95% CI, 2.05-17.45). Differences were maintained when the two control
      groups were separately analyzed. The distribution of positive criteria for the
      metabolic syndrome was reduced only in the metformin arm (p= 0.001, signed rank
      test). A control biopsy in 17 metformin-treated cases (14 nonresponders) showed a
      significant decrease in liver fat (p= 0.0004), necroinflammation, and fibrosis
      (p= 0.012 for both). No side effects were observed during metformin treatment.
      CONCLUSIONS: Metformin treatment is better than a prescriptive diet or vitamin E
      in the therapy of NAFLD patients receiving nutritional counseling. Limited
      histological data support an association between improved aminotransferases and
      biopsy findings, which require confirmation in a double-blind trial with
      appropriate statistical power based on liver histology.

PMID- 15842583
TI  - Factors associated with the presence of nonalcoholic steatohepatitis in patients
      with chronic hepatitis C.
AB  - OBJECTIVES: The aim of this study was to identify factors associated with the
      presence of nonalcoholic steatohepatitis (NASH) in patients with chronic
      hepatitis C (CHC). METHODS: We studied 98 patients with CHC [47 with NASH (group
      HCV/NASH), 51 without NASH (group HCV)] and 85 with NASH not infected with
      hepatitis C virus (HCV) (group NASH). We determined factors associated with the
      presence of NASH in patients with hepatitis C. RESULTS: Group HCV/NASH patients
      resembled those with NASH. Body mass index (BMI) was higher in group HCV/NASH
      than in group HCV, but was similar to group NASH. Most HCV/NASH patients had risk
      factors for NASH. In patients infected with HCV, NASH and NASH-related lesions
      were independently associated with BMI, while steatosis score was associated with
      HCV genotype 3 and BMI. Fibrosis stage was independently associated with
      steatosis, necroinflammatory activity index, and NASH lesions. CONCLUSION: While
      HCV genotype 3 infection and BMI are associated with the presence of steatosis in
      CHC, BMI is the only factor independently associated with the presence of NASH in
      these patients. We suggest that overweight-related factors might induce NASH in
      CHC patients.

PMID- 15842585
TI  - Evaluation of fatigue in U.S. patients with primary biliary cirrhosis.
AB  - OBJECTIVES: Fatigue, which may have a significant impact on quality of life, is
      the most common reported symptom in primary biliary cirrhosis (PBC). Multiple
      instruments to quantify fatigue and quality of life in liver disease have been
      validated, but have not been broadly applied to U.S. PBC patients. This study
      examines the extent of fatigue and its effect on quality of life in U.S. PBC
      patients. METHODS: Seventy patients with PBC were administered two validated
      questionnaires about quality of life (the Mayo version of the NIDDK-QA) and
      fatigue (the Fisk Fatigue Impact Score) and a proposed physical measure of
      fatigue in PBC (the grip strength test) on the day of routine physician visit.
      Nonparametric methods were employed. RESULTS: The fatigue and quality of life
      domain scores (physical functioning, liver symptoms, health satisfaction,
      Karnofsky index) discriminated between patients with and without self-reported
      fatigue (p < 0.05), as opposed to the grip strength results. Fatigue and quality
      of life domains correlated strongly with each other (r between 0.33 and 0.74,
      p</= 0.006) and not with the grip strength results. Neither quality of life nor
      fatigue scores correlated with age. CONCLUSIONS: The correlation between fatigue
      and quality of life scores suggests fatigue has an impact on quality of life in
      U.S. primary biliary cirrhosis patients. However, our fatigue scores suggest U.S.
      PBC patients have less fatigue than non-U.S. PBC patients. The grip strength is
      an insensitive measure of fatigue in U.S. PBC patients.

PMID- 15842584
TI  - Effect of lamivudine therapy on the serum covalently closed-circular (ccc) DNA of
      chronic hepatitis B infection.
AB  - OBJECTIVE: To determine the effect of 1-yr lamivudine treatment on serum
      covalently closed-circular DNA (cccDNA) level. PATIENTS AND METHOD: Serum total
      HBV DNA and cccDNA levels at baseline, week 24, and week 52 were measured in 82
      lamivudine-treated patients, 17 of whom received 1-yr placebo and acted as
      controls. RESULTS: There was a significant reduction in the cccDNA levels from
      baseline (median 3.0 x 10(6) copies/ml) to week 24 (33,476 copies/ml) and week 52
      (48,694 copies/ml) (p < 0.001 for both). The median reduction in cccDNA level at
      week 24 and 52 were 2.21 and 2.12 logs, respectively, which were significantly
      greater than those of controls (0.31 log, p < 0.001; 0.2 log, p < 0.001,
      respectively). Fifteen patients (18.3%) developed YMDD mutations by week 52.
      Compared to patients without YMDD mutations, patients with YMDD mutations had
      significantly less median reduction of total HBV DNA level (4.44 vs 3.65 logs,
      respectively, p= 0.02) and cccDNA level (2.27 vs 1.65 logs, respectively, p=
      0.016) at week 24 and significantly less median reduction of cccDNA at week 52
      (2.35 vs 0.8 logs respectively, p < 0.001). CONCLUSIONS: One-year lamivudine
      treatment decreased serum cccDNA level by 2 logs. The chance of YMDD mutations at
      week 52 was related to the magnitude of viral suppression at week 24.

PMID- 15842587
TI  - Comparison between prospective and retrospective evaluation of Crohn's disease
      activity index.
AB  - The Crohn's disease activity index (CDAI) is the most widely used measure of
      clinical disease activity in patients entered into clinical trials. The
      prospective nature of the CDAI calculation precludes its use as a clinical
      assessment tool. We compared the retrospective evaluation of the CDAI with the
      prospective evaluation in a heterogeneous patient population of 100 patients with
      Crohn's disease. The correlation between the two assessment methods was good with
      an r-value of 0.84 (p < 0,0001). There was a tendency of patients with a high
      retrospective CDAI to have a lower prospective CDAI which is explained by
      intention to treat. This study shows that a retrospective assisted evaluation of
      the CDAI is as accurate as the traditional prospective evaluation.

PMID- 15842586
TI  - Cardiac, neuroadrenergic, and portal hemodynamic effects of prolonged aldosterone
      blockade in postviral child A cirrhosis.
AB  - OBJECTIVES: The present study was designed to determine the effects of long-term
      antialdosterone treatment on cardiac structural and functional alterations,
      portal and systemic hemodynamic as well as adrenergic dysfunction characterizing
      Child A cirrhotic patients with F1 esophageal varices. METHODS: Twenty-two Child
      A postviral preascitic cirrhotic patients were randomly allocated to 200 mg/day K
      Canrenoate (13 patients, age 59.6 +/- 2.2 yr, mean + SEM) or no-drug treatment (9
      patients, age 61.8 +/- 2.3) for a 6-month-period. Measurements, which included
      hepatic venous pressure gradient (HVPG), left ventricular wall thickness, left
      ventricular end-diastolic volume and diastolic function (LVWT, LVEDV, and E/A
      ratio, echocardiography), and muscle sympathetic nerve activity (MSNA,
      microneurography, peroneal nerve), were obtained at baseline and following 6
      months of drug or no-drug treatment. Ten healthy age-matched subjects served as
      controls. RESULTS: Cirrhotic patients were characterized by increased HVPG, LVWT,
      and MSNA values and by a depressed E/A ratio. K-Canrenoate treatment
      significantly reduced HVPG (from 15.3 +/- 1.0 to 13.8 +/- 0.8 mmHg, p < 0.05),
      LVWT (from 21.8 +/- 0.5 to 20.7 +/- 0.6 mm, p < 0.02), and LVEDV (from 99.2 +/- 7
      to 86.4 +/- 6 ml, p < 0.01), leaving E/A ratio and MSNA almost unaltered. No
      significant change was observed in the untreated group of cirrhotic patients
      followed for 6 months without intervention. CONCLUSIONS: These data provide
      evidence that aldosterone blockade by long-term K-Canrenoate administration
      improves hepatic hemodynamics by lowering HVPG and ameliorates cardiac structure
      and function by favoring a reduction in LVWT and LVEDV as well. They also show,
      however, that this therapeutic intervention neither improves left ventricular
      diastolic dysfunction nor exerts sympathoinhibitory effects.

PMID- 15842588
TI  - Increased rates of early adverse reaction to azathioprine in patients with
      Crohn's disease compared to autoimmune hepatitis: a tertiary referral center
      experience.
AB  - OBJECTIVES: Idiosyncratic drug hypersensitivity may occur at increased rates in
      specific patient populations. Azathioprine has a significant early adverse
      reaction (EAR) profile, which includes an acute syndrome of constitutional
      symptoms, fever, rash, and acute pancreatitis and often requires discontinuation
      of drug. EAR precludes azathioprine use in patients with Crohn's disease (CD) and
      autoimmune hepatitis (AIH). Our aims were to investigate differential rates of
      EAR to azathioprine in CD compared to AIH in a tertiary referral center
      population. METHODS: Retrospective chart review of consecutive CD and AIH
      patients who were initiated on azathioprine in our inflammatory bowel disease
      (IBD) and hepatology centers was performed. EAR (fevers and constitutional
      symptoms, severe arthralgias, nausea, and vomiting) were defined as those
      occurring within 1 month of initiation. EAR rates between AIH and CD patients
      were compared using the Fisher's exact test. RESULTS: One hundred and forty-three
      CD (88F/55M; age 39.2 +/- 13 yr) and 40 AIH (35F/5M; age 53.1 +/- 14 yr) patients
      were studied. All patients were initiated with equivalent azathioprine dosage (50
      mg qd). All AIH patients were on prednisone (mean daily dose 7.5 mg) compared to
      51% of CD patients (median daily dose 20 mg). EAR rates were significantly higher
      in CD patients (42/143; 29%) compared to AIH (2/40; 5%) (Fisher's exact test; p=
      0.008). EAR excluding nausea and vomiting were still significantly higher in CD
      patients (27/143; 19%) compared to AIH (1/40; 2.5%) (Fisher's exact test; p=
      0.01). All patients with EAR required drug discontinuation and 7% of CD patients
      required hospitalization for management of these complications. CONCLUSIONS: CD
      patients represent a unique subgroup at increased risk of EAR to azathioprine.
      Mechanisms behind these reactions need to be further defined.

PMID- 15842589
TI  - Tumor necrosis factor receptor gene polymorphisms in Crohn's disease: association
      with clinical phenotypes.
AB  - OBJECTIVES: Crohn's disease (CD) is a chronic multifactorial disorder with
      diverse clinical features that are influenced by a heterogeneous set of genetic
      factors. TNF-alpha/TNF receptor interactions play a pivotal role in the
      pathogenesis of the inflammatory response. Our purpose was to determine whether
      single nucleotide polymorphisms (SNPs) in the TNF receptors confer susceptibility
      to Crohn's disease and whether they are associated with clinical phenotype.
      METHODS: A cohort of 205 consecutively identified and unrelated patients with CD
      and 106 controls were recruited. Subjects were genotyped for polymorphisms in
      TNFRSF1A (position +36, -609), TNFRSF1B (+196, +1466), along with the three
      common CARD15 variants and phenotyped for disease behavior. Genotypic and allelic
      frequencies were compared between CD and controls and a logistic regression model
      was constructed to determine independent associations with specific clinical
      phenotypes. RESULTS: Only the TNFRSF1A +36 and TNFRSF1B +196 SNPs were associated
      with CD (p= 0.0019 and 0.034, respectively). The TNFRSF1A +36 mutation was
      negatively associated with stricturing disease phenotype (OR = 0.384; CI = 0.166
      0.887). In contrast, the TNFRSF1B +196 was negatively associated with colitis (OR
      = 0.410; CI = 0.191-0.880). These associations were independent of CARD15
      mutation status. Finally, TNFRSF1B +196 was negatively associated with surgery in
      CARD15 negative patients. CONCLUSIONS: These data constitute the first report of
      an association of TNFRSF1A and TNFRSF1B polymorphisms with CD in a Caucasian
      population and address the role of TNFR mutations in determining clinical
      heterogeneity in CD.

PMID- 15842590
TI  - The role of cytokine gene polymorphisms in determining disease susceptibility and
      phenotype in inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: Emerging data indicate that alterations in cytokine
      synthesis may play a role in inflammatory bowel disease (IBD) pathogenesis. The
      differential production of cytokines has been linked to single nucleotide
      polymorphisms in gene promoter regions, signal sequences, and gene introns. The
      aim of this study was to assess the relationship between polymorphisms involving
      five cytokine genes (TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma), and IBD
      susceptibility and disease phenotype. METHODS: Cytokine genotyping was performed
      utilizing polymerase chain reaction. The specific gene polymorphisms that were
      probed for included: -1082(G/A), -819(T/C), and -592(A/C) in the IL-10 promoter, 
      308(G/A) in the TNF-alpha promoter, codon 10 (T/C), and codon 25 (G/C) of the TGF
      beta signal sequence, +874(T/A) of intron 1 of IFN-gamma, and -174(C/G) in the IL
      6 promoter. RESULTS: A total of 193 IBD patients (138 Crohn's disease (CD) and 55
      ulcerative colitis (UC)) and 92 controls were evaluated. No association between
      IBD, UC, or CD susceptibility and the cytokine gene polymorphisms were found.
      Patients with ileocolonic CD were more likely to possess the IL-6 -174 GG
      genotype compared to those with nonileocolonic disease (p= 0.006). Patients with
      ileal CD were more likely to possess the IL-6 -174 GC genotype compared to those
      with nonileal disease (p= 0.0004). An increased number of CD patients with
      isolated colonic disease possessed the IL-6 -174 CC genotype compared to those
      with nonisolated colonic disease (p= 0.032). CONCLUSION: The cytokine gene
      polymorphisms studied here do not appear to influence IBD susceptibility. There
      does, however, appear to be an influence on disease phenotype, particularly on CD
      site.

PMID- 15842591
TI  - Low rate of microsatellite instability in young patients with adenomas:
      reassessing the Bethesda guidelines.
AB  - BACKGROUND AND AIM: Screening adenomas for microsatellite instability (MSI) in
      patients younger than 40 yr of age has been recommended by the Bethesda
      Guidelines as a means of identifying patients at risk for hereditary nonpolyposis
      colorectal cancer (HNPCC). We sought to determine the rate of MSI in adenomas
      removed from individuals under 40 yr of age over a 5-yr period in a university
      general gastroenterology practice. METHODS: We identified patients between 18 and
      39 yr of age with endoscopically removed adenomatous colorectal polyps. Patients
      with polyposis syndromes, inflammatory bowel disease, or colorectal carcinoma
      were excluded. A three-generation family history was obtained via telephone
      interview. Endoscopic and histology reports were reviewed. Adenomas were tested
      for MSI using the BAT26 and BAT40 microsatellite markers, and expression of the
      MSH2 and MLH1 proteins was assessed by immunostaining. RESULTS: A total of 34
      patients had 46 adenomas removed endoscopically. Out of 34 patients, 14 (41%) had
      a family history of colorectal cancer and 3 were from Amsterdam criteria positive
      families. A total of 28 of 46 adenomas (61%) were distal to the splenic flexure.
      Polyps ranged in size from 2 to 20 mm and averaged 6.6 mm. Five polyps (11%) were
      tubulovillous adenomas, and the remainder were tubular adenomas. None of the
      polyps were serrated adenomas and none demonstrated high-grade dysplasia. Among
      the 40 adenomas available for testing, none demonstrated MSI using either BAT26
      (0/40) or BAT40 (0/21), nor did any of the polyps tested demonstrate loss of
      either MSH2 or MLH1 expression (0/16). CONCLUSION: Screening adenomas from
      patients younger than 40 yr of age for MSI was ineffective in identifying
      potentially new cases of HNPCC. New strategies that improve on the current
      clinical and molecular screening methods should be developed so that at-risk
      individuals can be identified and referred for germline testing before developing
      their first cancer.

PMID- 15842592
TI  - Adenomas in young patients: what is the optimal evaluation?
AB  - Colorectal adenomas are a known risk factor for colorectal cancer. The prevalence
      of colorectal adenomas among individuals under age 40 and the clinical
      implications of finding a single adenoma in a young individual have not been
      defined. Until the most recent revision of the Bethesda Guidelines, having one or
      more adenomas diagnosed at age <40 was an indication for evaluation for
      hereditary nonpolyposis colorectal cancer (HNPCC). In an effort to explore the
      association of young-onset adenomas with HNPCC, Velayos et al. tested adenomas
      from 34 subjects aged 18-39 for pathologic features of HNPCC. Finding that none
      of the young-onset adenomas demonstrated features of microsatellite instability
      (MSI) or loss of mismatch repair protein expression by immunohistochemistry
      (IHC), the authors conclude that the yield of such testing is low, and support
      the decision to exclude young-onset adenomas from the Revised Bethesda Guidelines
      for HNPCC. However, this study also revealed that MSI and IHC failed to detect
      abnormalities in half of the adenomas from control subjects with identified MLH1
      and MSH2 mutations. These findings highlight the limitations of current molecular
      techniques for examining adenomas as an initial screen for HNPCC and the need for
      further studies evaluating the optimal genetic and clinical evaluation of
      patients with young-onset adenomas.

PMID- 15842593
TI  - Risk of colorectal neoplasm in patients with acromegaly and its relationship with
      serum growth hormone levels.
AB  - OBJECTIVES: Acromegalics have been reported to be at an increased risk of
      colorectal neoplasm. However, the magnitude of the risk is still controversial
      and the mechanism has not been fully investigated. In this study, we attempted to
      determine the magnitude of the association between acromegaly and colorectal
      lesions after taking into account age, gender, smoking status, and treatment
      status. In addition, we assessed the relationship between colorectal lesions and
      serum growth hormone (GH) levels in acromegalics. METHODS: We conducted a case
      control study by using 19 consecutive untreated patients (male:female = 11:8) who
      were newly diagnosed with acromegaly between 1990 and 2000. All patients
      underwent colonoscopy and received a histological diagnosis of colorectal
      lesions. Prevalence of hyperplastic polyp, adenoma, and carcinoma were compared
      with the prevalence in 76 controls matched for gender, age, and smoking status.
      Serum GH levels were compared between acromegalic patients with and without each
      type of colorectal lesion. RESULTS: The prevalence of hyperplastic polyp,
      adenoma, and carcinoma were significantly higher in the acromegalic patients
      compared to the controls (p < 0.05, odds ratios; 8.3, 4.2, and 9.8,
      respectively). In acromegalics, the presence of hyperplastic polyps and
      carcinomas were significantly associated with higher serum GH levels after
      adjusting for the other lesions and age (p < 0.05). CONCLUSIONS: After
      controlling for age, gender, smoking status, and treatment status, acromegaly was
      associated with significantly higher prevalence of colorectal hyperplastic polyp,
      adenoma, and carcinoma. High serum GH levels may be associated with the presence
      of hyperplastic polyp and carcinoma.

PMID- 15842594
TI  - The effect of moderate sedation on exocrine pancreas function in normal healthy
      subjects: a prospective, randomized, cross-over trial using the synthetic porcine
      secretin stimulated Endoscopic Pancreatic Function Test (ePFT).
AB  - BACKGROUND: We have developed a purely endoscopic collection method for the
      assessment of pancreatic secretory function (ePFT). The pancreatic secretory
      effects of sedation medications utilized during endoscopic procedures are not
      completely known. AIMS: To study the effect of moderate sedation on the exocrine
      pancreas gland in a prospective, randomized trial. METHODS: Healthy volunteers
      were randomized by computers to one of two treatments (A-no sedation, B-sedation)
      in period 1 and crossed-over to the other treatment in period 2 with a minimal
      washout interval of 7 days. Sedation dosage was standardized for each patient
      based on age, gender and weight from a previously published dosing nomogram.
      Synthetic porcine secretin (ChiRhoClin, Inc., Burtonsville, Maryland) was used as
      the pancreatic stimulant. Duodenal fluid samples were aspirated via the endoscope
      every 5 min for 1 h and sent on ice to our hospital laboratory for the
      measurement of pancreatic secretory electrolyte concentrations by autoanalyzer.
      RESULTS: A total of 17 healthy volunteers were enrolled. Sixteen subjects (8
      males and 8 females) completed the randomized prospective trial. Median
      intravenous meperidine and midazolam sedation dose was 62.5 mg and 2.5 mg,
      respectively. Maximum pancreatic juice flow occurred during the early phase of
      secretion and maximum bicarbonate concentration occurred during the late phase of
      secretion. Analysis of the electrolyte composition of the endoscopically
      collected duodenal drainage fluid revealed a constant cation concentration for
      both sodium and potassium over the 1 h collection period. The anions, chloride
      and bicarbonate, exhibited a reciprocal relationship identical to that seen in
      traditional gastroduodenal tube collection studies. There was no statistical
      difference observed between the sedation and no sedation groups. The estimated
      total bicarbonate output (area under curve, AUC) for the sedated and non-sedated
      groups were 5,017 meq + 724 (range 3,663-6,173) and 5,364 meq +/- 583 (range
      4,323-6563) respectively (p= 0.0656). The mean peak bicarbonate concentrations
      for sedated (n = 8) versus non-sedated (n = 8) groups were 103 +/- 11 meq/L
      (range 78-125) and 106 +/- 11 meq/L (range 87-138), respectively (p= 0.1346).
      There was excellent correlation of peak bicarbonate concentrations when sedation
      and no sedation groups were compared (r= 0.744, p < 0.05; Spearman rank
      correlation). There were no episodes of pancreatitis. CONCLUSIONS: (a) Moderate
      sedation used for upper endoscopy does not effect the clinical diagnostic
      parameters (peak bicarbonate concentration or total bicarbonate output) utilized
      to diagnose pancreatic insufficiency. (b) Analysis of duodenal drainage fluid
      collected endoscopically after synthetic secretin stimulation produces an
      identical pancreatic secretory curve described with traditional gastroduodenal
      tube collection methods.

PMID- 15842595
TI  - Immunosuppressive therapy in Whipple's disease patients is associated with the
      appearance of gastrointestinal manifestations.
AB  - OBJECTIVES: Whipple's disease is a rare chronic disorder, which is caused by
      systemic infection with Tropheryma whipplei. The first symptom of Whipple's
      disease usually is a nondestructive polyarthritis resembling in many aspects
      seronegative rheumatoid arthritis. This polyarticular inflammatory arthropathy
      preceding the diagnosis of Whipple's disease for several years frequently is
      treated with nonsteroidal antiinflammatory drugs (NSAIDs) and with
      immunosuppressive therapy. There is evidence that altered immune functions play a
      role in the manifestation of the disease and that Whipple's disease is associated
      with opportunistic infections. We therefore asked whether immunosuppressive
      treatment for arthropathy may alter the course of Whipple's disease. PATIENTS AND
      METHODS: In a series of 27 patients with Whipple's disease clinical data were
      documented and the patients were followed for 3-4 yr. The patients were
      classified into three groups according to their medication: (i) patients with
      immunosuppressive therapy preceding the diagnosis, (ii) patients with NSAIDs
      before diagnosis, and (iii) patients without such therapies. RESULTS:
      Arthropathies occurred in the mean 8 yr before diagnosis and were the first
      symptom in 63% of the patients. Gastrointestinal involvement usually became
      evident later on and frequently led to the diagnosis of Whipple's disease. In
      patients with immunosuppressive treatment, diarrhea occurred in the median 4
      months after the initiation of such therapy and diagnosis of Whipple's disease
      was made after another 2 months. In contrast, other medical treatments were not
      closely followed by the onset of diarrhea. CONCLUSIONS: These results indicate an
      association between immunosuppressive therapy and the onset of diarrhea in
      Whipple's disease and thus support the concept that immunologic factors play a
      role in disease pathogenesis. Further investigation on the interaction of the
      immune system and Tropheryma whipplei infection are required to understand the
      factors contributing to the clinical manifestation of this rare disorder and
      possibly to introduce preventive interventions.

PMID- 15842596
TI  - Bowel habit subtypes and temporal patterns in irritable bowel syndrome:
      systematic review.
AB  - Irritable bowel syndrome (IBS) is a heterogeneous condition characterized by the
      presence of abdominal discomfort or pain and bowel habit alterations:
      constipation (C-IBS), diarrhea (D-IBS), or alternating C and D (A-IBS). Its
      clinical course is poorly known. OBJECTIVES: (i) To compare bowel habit subtypes
      distribution in IBS according to sample origin and diagnosis criteria; (ii) To
      evaluate IBS temporal patterns based on follow-up studies. METHODS: A literature
      search (1966-2003) was conducted in the MEDLINE and EMBASE databases. A total of
      72 studies were found and 22 were finally selected. RESULTS: Population-based
      studies from the United States (Manning) found similar distribution among C-IBS,
      D-IBS, and A-IBS, while European studies (Rome I, Rome II, or self-reporting)
      showed either C-IBS or A-IBS as the most prevalent subtypes. Primary care office
      based studies (Rome I or Rome II) showed A-IBS as the most prevalent group.
      Gastroenterology specialized office-based studies found either C-IBS or D-IBS as
      the most frequently reported subtype. Prospective follow-up investigations showed
      that the most frequent IBS temporal pattern profile consists of mild to moderate
      symptoms appearing in cluster in an intermittent way, about once a week, and
      lasting 2-5 days on average. CONCLUSION: IBS clinical subtypes distribution
      differs depending on the population evaluated, the geographical location, and the
      criteria employed to define IBS and bowel habit subtypes. In most cases, clinical
      course is characterized by the presence of mild-to-moderate symptoms appearing
      sequentially. Prospective studies, using clear and stable diagnostic criteria and
      subtype definitions, and based on daily data collection should further
      characterize IBS clinical course.

PMID- 15842597
TI  - The evaluation of hyperferritinemia: an updated strategy based on advances in
      detecting genetic abnormalities.
AB  - The number of new genes implicated in iron metabolism has dramatically increased
      during the last few years. Alterations of these genes may cause hyperferritinemia
      associated or not with iron overload. Correct assignment of the specific disorder
      of iron metabolism requires the identification of the causative gene mutation.
      Here, we propose a rational strategy that allows targeting the gene(s) to be
      screened for a diagnostic purpose. This strategy relies on the age of onset of
      the disease, the type of clinical symptoms, the biochemical profile (elevated or
      normal serum transferrin saturation (TfSat)), the presence or not of visceral
      iron excess, and the mode of inheritance (autosomal recessive or dominant). Then,
      two main entities can be differentiated: genetic (adult or juvenile)
      hemochromatosis characterized by elevated TfSat, and hereditary
      hyperferritinemias where TfSat is normal (or only slightly modified). Adult
      genetic hemochromatosis (GH) is related mainly to mutations of the HFE gene, and
      exceptionally to mutations of the TFR2 gene. Juvenile GH is a rare condition
      related principally to mutations of the HJV gene coding for hemojuvelin, and
      rarely to mutations of the HAMP gene coding for hepcidin. Hereditary
      hyperferritinemias are linked to mutations of three genes: the L-ferritin gene
      responsible for the hereditary hyperferritinemia cataract syndrome (without iron
      overload), the ferroportin gene leading to a dominant form of iron overload, and
      the ceruloplasmin (CP) gene corresponding to an iron overload syndrome with
      neurological symptoms. The proposed strategic approach may change with the
      identification of other genes involved in iron metabolism.

PMID- 15842598
TI  - Chronic liver disease and consumption of raw oysters: a potentially lethal
      combination--a review of Vibrio vulnificus septicemia.
AB  - Vibrio vulnificus septicemia is the most common cause of fatality related to
      seafood consumption in the United States. It occurs predominantly in patients
      with chronic liver disease following consumption of raw oysters. V. vulnificus is
      a highly virulent human pathogen, normally found in warm estuarine and marine
      environment. It lodges in filter feeders like oysters. The onset of this illness
      is abrupt, rapidly progressing to septic shock with a high mortality. Clinicians
      managing patients with chronic liver disease need to educate their patients of
      the risk associated with the consumption of raw seafood, especially oysters. A
      high index of suspicion is necessary for appropriate treatments, as doxycycline,
      the antibiotic of choice, is not usually a part of the empiric therapy for
      septicemia. The high mortality associated with this septicemia demands aggressive
      preventive measures: susceptible individuals must be forewarned by signs
      displayed in restaurants; physicians must educate patients with chronic liver
      disease about the risk of raw oyster consumption; and harvesting methods which
      reduce contamination by V. vulnificus must be utilized.

PMID- 15842599
TI  - The prevalence of autoantibodies and autoimmune hepatitis in patients with
      nonalcoholic fatty liver disease.

PMID- 15842601
TI  - The second most important maneuver during colonoscopy.

PMID- 15842603
TI  - Restarting the gastroenterology match.

PMID- 15842604
TI  - Endoscopic insertion of self-expanding metal stents as first step to treat
      malignant colorectal obstruction.

PMID- 15842605
TI  - Science and politics of propofol.

PMID- 15842607
TI  - The relative effects of different systemic immunosuppressives on skin cancer
      development in organ transplant patients.
AB  - The immunosuppressive medications used in organ transplant recipients (OTRs) to
      prevent allograft rejection are associated with an increased incidence of skin
      cancer in this population. Several classes of immunosuppressive agents exist, and
      the selection of which medication to use varies by organ type and with time. The
      tumorigenic potential and relative effects of different immunosuppressive
      medications on skin cancer risk have been studied. This article reviewed the
      history of the immunosuppressive agents and their mechanisms of action. A summary
      of the current literature on the relationship between skin cancer and the
      different immunosuppressives were included. Guidelines for management of OTRs in
      dermatologic practice were discussed.

PMID- 15842608
TI  - Management of skin cancer in solid organ transplant recipients.
AB  - The incidence of catastrophic skin cancer in the solid organ transplant
      population continues to rise. As transplant patients are living longer, it is
      likely that dermatologists will be looking after an increasing number of organ
      transplant recipients. The key to managing this patient population lies in a
      multidisciplinary approach encompassing patient education, skin screening in the
      immediate post-transplant period, regular follow-up, and rapid referral to a
      dermatologist once skin lesions suspicious for skin cancer are diagnosed. Of
      paramount importance is discussion with transplant physicians to negotiate
      reduction of immunosuppression in the setting of catastrophic skin cancer. This
      article defines the scope of the problem of skin cancer in the solid organ
      transplant population, defines the nature of the lesions commonly presented, and
      reinforces the benefit of a multidisciplinary approach in the management of these
      patients.

PMID- 15842609
TI  - Use of topical immunomodulators in organ transplant recipients.
AB  - Solid organ transplant recipients are a growing population at increased risk for
      the development of cutaneous premalignant and malignant lesions, resulting in
      significant morbidity and mortality. Topical immunomodulators, in particular
      imiquimod, have shown efficacy in the management of multiple malignant,
      precancerous, and viral conditions. The ability to locally induce an immune
      response, presumably against tumor and viral antigens, and induce apoptosis makes
      topical immunomodulators a promising therapeutic option in organ transplant
      recipients. Although limited, data have begun to accumulate on the use of
      imiquimod in transplant patients for the management of superficial, nodular, and
      infiltrative basal cell carcinomas; in situ and invasive squamous cell
      carcinomas; condyloma acuminata; and common warts. As more experience is
      gathered, the role of imiquimod and other topical immunomodulators in the care of
      OTRs will be clarified. The authors reviewed the existing data on the use of
      topical imiquimod in OTRs with mention of its presumed mechanisms of action and
      other immunomodulators with potential efficacy against cancerous and precancerous
      lesions.

PMID- 15842610
TI  - Practical retinoid chemoprophylaxis in solid organ transplant recipients.
AB  - Solid organ transplant recipients are at a significantly increased risk of
      developing skin cancer. Both systemic and topical retinoids are useful for
      chemosuppression of skin cancer in this patient population. These drugs can
      reduce both the present extent and the future development of premalignant and
      malignant skin lesions. This paper reviews the current data on the
      chemoprophylactic properties of topical and systemic retinoids. A practical guide
      for their use in organ transplant recipients is provided. Specific
      recommendations for implementing and maintaining therapy, as well as appropriate
      management and monitoring of adverse events, are presented.

PMID- 15842611
TI  - Management of nevi in transplant patients.
AB  - Immunosuppression is known to be an independent risk factor for melanoma. As
      allograft-sparing therapies have improved in the past two decades and transplant
      recipients have longer survival rates, the numbers of patients at increased risk
      for cutaneous malignancies, including melanoma, have dramatically grown. For a
      majority of transplant recipients, the first opportunity for skin cancer
      screening and patient education does not begin prior to transplantation, nor does
      it involve a dermatologist. Dermatologists detect thinner melanomas when compared
      to those detected by other physicians, including other specialists. A dermatology
      consultation for assessment of individual risk and a baseline physical
      examination should be done as part of a pretransplant evaluation for every
      patient. The authors review the known risk factors for cutaneous melanoma and
      melanocytic nevi in both immunocompetent and immunosuppressed populations and
      current methods of examination and management of pigmented lesions, including
      brief discussions of a multidisciplinary approach, and when to consider
      decreasing or stopping immunosuppressive therapy.

PMID- 15842612
TI  - Evaluation and management of fungal infections in immunocompromised patients.
AB  - As the population of chronically immunosuppressed individuals continues to grow,
      the prevalence of fungal infections is increasing. Fungal infections in this
      patient population represent challenges in diagnosis and management. This article
      will review the common superficial and invasive mycoses that occur in the solid
      organ transplant and HIV-infected populations. Disease presentations are
      reviewed, but emphasis is placed on cutaneous manifestations. Recent advances in
      antifungal therapy and their direct application to specific diseases provide
      important new approaches to this complex and often seriously ill patient
      population.

PMID- 15842613
TI  - Cutaneous effects of highly active antiretroviral therapy in HIV-infected
      patients.
AB  - Effective highly active antiretroviral therapy (HAART) has increased survival in
      patients infected with the human immunodeficiency virus (HIV). However, HAART is
      not without toxicities. Cutaneous adverse reactions from antiretroviral agents
      have become increasingly important to recognize as the population of patients
      surviving with HIV infection grows. Dermatologists play an important role in
      managing these cutaneous effects of HAART therapy in HIV patients. This article
      reviews cutaneous adverse effects from nucleoside reverse transcriptase
      inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors,
      and fusion inhibitors, as well as separately addresses lipodystrophy, and immune
      reconstitution.

PMID- 15842614
TI  - Human papillomavirus anogenital disease in HIV-infected individuals.
AB  - Human papillomavirus (HPV) is one of the most common sexually transmitted
      infections and a significant cause of anogenital malignancies, precancer lesions,
      and cutaneous disease. Human immunodeficiency virus (HIV)-positive individuals
      have a higher prevalence of HPV infection and HPV-associated anogenital disease
      compared to age-matched HIV-negative controls. Data suggest that there has been
      little reduction in HPV-associated disease since the introduction of highly
      active antiretroviral therapy (HAART). The authors believe that cervical and anal
      cancer screening using Pap tests should be offered to all HIV-positive
      individuals, but the infrastructure to identify (via colposcopy and high
      resolution anoscopy) and treat precancer lesions must be present. Treatment of
      HPV-associated anogenital disease depends on the size, location, and grade of the
      lesion, whereas a variety of ablative and excisional therapies are available.
      Prophylactic and therapeutic HPV vaccines are promising as future interventions
      for disease control in at-risk populations such as HIV-infected women and men.

PMID- 15842615
TI  - Approach to the treatment of cutaneous malignancy in HIV-infected patients.
AB  - Patients infected with human immunodeficiency virus (HIV) have an increased risk
      of developing skin cancers. These at-risk patients may have atypical
      presentations and/or altered clinical courses. This article will review and
      discuss management issues for the following malignancies: lymphomas, malignant
      melanoma, basal cell carcinoma, squamous cell carcinoma, and Kaposi's sarcoma.

PMID- 15842616
TI  - Stylar glycoproteins bind to S-RNase in vitro.
AB  - S-RNases determine the specificity of S-specific pollen rejection in self
      incompatible plants of the Solanaceae, Rosaceae, and Scrophulariaceae. They are
      also implicated in at least two distinct types of unilateral interspecific
      incompatibility in Nicotiana. However, S-RNase itself is not sufficient for most
      types of pollen rejection, and evidence for its direct interaction with pollen
      tubes is limited. Thus, non-S-RNase factors also are required for pollen
      rejection. As one approach to identifying such factors, we tested whether SC10
      RNase from Nicotiana alata would bind to other stylar proteins in vitro. SC10
      RNase was immobilized on Affi-gel, and binding proteins were analyzed by SDS-PAGE
      and immunoblotting. In addition to SC10-RNase and a small protein similar to lily
      chemocyanin, the most prominent binding proteins include NaTTS, 120K, and
      NaPELPIII, these latter three being arabinogalactan proteins previously shown to
      interact directly with pollen tubes. We also show that SC10-RNase and these
      glycoproteins migrate as a complex in a native PAGE system. Our hypothesis is
      that S-RNase forms a complex with these glycoproteins in the stylar ECM, that the
      glycoproteins interact directly with the pollen tubes and thus that the initial
      interaction between the pollen tube and S-RNase is indirect.

PMID- 15842617
TI  - Identification of a novel cis-acting element conferring sulfur deficiency
      response in Arabidopsis roots.
AB  - SULTR1;1 high-affinity sulfate transporter is highly regulated in the epidermis
      and cortex of Arabidopsis roots responding to sulfur deficiency (-S). We
      identified a novel cis-acting element involved in the -S-inducible expression of
      sulfur-responsive genes in Arabidopsis. The promoter region of SULTR1;1 was
      dissected for deletion and gain-of-function analysis using luciferase (LUC)
      reporter gene in transgenic Arabidopsis. The 16-bp sulfur-responsive element
      (SURE) from -2777 to -2762 of SULTR1;1 promoter was sufficient and necessary for
      the -S-responsive expression, which was reversed when supplied with cysteine and
      glutathione (GSH). The SURE sequence contained an auxin response factor (ARF)
      binding sequence (GAGACA). However, SURE was not responsive to naphthalene acetic
      acid, indicating its specific function in the sulfur response. The base
      substitution analysis indicated the significance of a 5-bp sequence (GAGAC)
      within the conserved ARF binding site as a core element for the -S response.
      Microarray analysis of early -S response in Arabidopsis roots indicated the
      presence of SURE core sequences in the promoter regions of -S-inducible genes on
      a full genome GeneChip array. It is suggested that SURE core sequences may
      commonly regulate the expression of a gene set required for adaptation to the -S
      environment.

PMID- 15842618
TI  - Callose synthase (CalS5) is required for exine formation during
      microgametogenesis and for pollen viability in Arabidopsis.
AB  - Callose (beta-1,3-glucan) is produced at different locations in response to
      biotic and abiotic cues. Arabidopsis contains 12 genes encoding callose synthase
      (CalS). We demonstrate that one of these genes, CalS5, encodes a callose synthase
      which is responsible for the synthesis of callose deposited at the primary cell
      wall of meiocytes, tetrads and microspores, and the expression of this gene is
      essential for exine formation in pollen wall. CalS5 encodes a transmembrane
      protein of 1923 amino acid residues with a molecular mass of 220 kDa. Knockout
      mutations of the CalS5 gene by T-DNA insertion resulted in a severe reduction in
      fertility. The reduced fertility in the cals5 mutants is attributed to the
      degeneration of microspores. However, megagametogenesis is not affected and the
      female gametes are completely fertile in cals5 mutants. The CalS5 gene is also
      expressed in other organs with the highest expression in meiocytes, tetrads,
      microspores and mature pollen. Callose deposition in the cals5 mutant was nearly
      completely lacking, suggesting that this gene is essential for the synthesis of
      callose in these tissues. As a result, the pollen exine wall was not formed
      properly, affecting the baculae and tectum structure and tryphine was deposited
      randomly as globular structures. These data suggest that callose synthesis has a
      vital function in building a properly sculpted exine, the integrity of which is
      essential for pollen viability.

PMID- 15842619
TI  - Multiplicity of different cell- and organ-specific import routes for the NADPH
      protochlorophyllide oxidoreductases A and B in plastids of Arabidopsis seedlings.
AB  - The NADPH-dependent protochlorophyllide (Pchlide) oxidoreductase (POR) is a
      photoenzyme that requires light for its catalytic activity and uses Pchlide
      itself as a photoreceptor. In Arabidopsis there are three PORs denoted PORA, PORB
      and PORC. The PORA and PORB genes are strongly expressed early in seedling
      development. In contrast to PORB the import of PORA into plastids of cotyledons
      is substrate-dependent and organ-specific. These differences in the import
      reactions between PORA and PORB most likely are due to different import
      mechanisms that are responsible for the uptake of these proteins. The two major
      core constituents of the translocon of the outer plastid envelope, Toc159 and
      Toc34, have been implicated in the binding and recognition of precursors of
      nuclear-encoded plastid proteins. Their involvement in conferring substrate
      dependency and organ specificity of PORA import was analyzed in intact
      Arabidopsis seedlings of wild type and the three mutants ppi3, ppi1 and ppi2 that
      are deficient in atToc34, atToc33, a closely related isoform of atToc34, and
      atToc159. Whereas none of these three Toc constituents is required for
      maintaining the organ specificity and substrate dependency of PORA import,
      atToc33 is indispensable for the import of PORB in cotyledons and true leaves
      suggesting that in these parts of the plant translocation of PORA and PORB occurs
      via two distinct import pathways. The analysis of PORA and PORB import into
      plastids of intact seedlings revealed an unexpected multiplicity of import routes
      that differed by their substrate, cell, tissue and organ specificities. This
      versatility of pathways for protein targeting to plastids suggests that in intact
      seedlings not only the constituents of the core complex of import channels but
      also other factors are involved in mediating the import of nuclear-encoded
      plastid proteins.

PMID- 15842620
TI  - A nuclear gene of Chlamydomonas reinhardtii, Tba1, encodes a putative
      oxidoreductase required for translation of the chloroplast psbA mRNA.
AB  - Biosynthesis of chloroplast proteins is to a large extent regulated post
      transcriptionally, and a number of nuclear-encoded genes have been identified
      that are required for translation or stability of specific chloroplast mRNAs. A
      nuclear mutant of Chlamydomonas reinhardtii, hf261, deficient in the translation
      of the psbA mRNA, has reduced association of the psbA mRNA with ribosomes and is
      deficient in binding of the chloroplast localized poly (A) binding protein
      (cPAB1) to the psbA mRNA. Cloning of the hf261 locus and complementation of hf261
      using a wt genomic clone has identified a novel gene, Tba1, for translational
      affector of psbA. Strains complemented with the wt Tba1 gene restore the ability
      of the psbA mRNA to associate with ribosomes, and restores RNA binding activity
      of cPAB1 for the psbA mRNA. Analysis of the Tba1 gene identified a protein with
      significant homology to oxidoreductases. The effect of Tba1 expression on the RNA
      binding activity of cPAB1, and on the association of psbA mRNA with ribosomes,
      implies that Tba1 functions as a redox regulator of cPAB1 RNA binding activity to
      indirectly promote psbA mRNA translation initiation. A model of chloroplast
      translation incorporating Tba1 and other members of the psbA mRNA binding complex
      is presented.

PMID- 15842621
TI  - Japanese morning glory dusky mutants displaying reddish-brown or purplish-gray
      flowers are deficient in a novel glycosylation enzyme for anthocyanin
      biosynthesis, UDP-glucose:anthocyanidin 3-O-glucoside-2''-O-glucosyltransferase,
      due to 4-bp insertions in the gene.
AB  - Bright blue or red flowers in the Japanese morning glory (Ipomoea nil) contain
      anthocyanidin 3-O-sophoroside derivatives, whereas the reddish-brown or purplish
      gray petals in its dusky mutants accumulate anthocyanidin 3-O-glucoside
      derivatives. The Dusky gene was found to encode a novel glucosyltransferase, UDP
      glucose:anthocyanidin 3-O-glucoside-2''-O-glucosyltransferase (3GGT), which
      mediates the glucosylation of anthocyanidin 3-O-glucosides to yield anthocyanidin
      3-O-sophorosides. Ipomoea nil carries one copy of the 3GGT gene that contains no
      intron and produces 1.6-kbp transcripts mainly in the petals and tubes of flower
      buds at around 24 h before flower opening. The gene products of both In3GGT in I.
      nil and Ip3GGT in the common morning glory (Ipomoea purpurea) comprise 459 amino
      acids and showed a close relationship to the petunia UDP-rhamnose:anthocyanidin 3
      O-glucoside-6''-O-rhamnosyltransferase (3RT), which controls the addition of a
      rhamnose molecule to anthocyanidin 3-O-glucosides for conversion into
      anthocyanidin 3-O-rutinosides. All of the 30 dusky mutants tested were found to
      carry the 4-bp insertion mutations GGAT or CGAT at an identical position near the
      3' end of the gene, and the insertions caused frameshift mutations. The expected
      3GGT enzymatic activities were found in the crude extracts of Escherichia coli,
      in which the 3GGT cDNA of I. nil or I. purpurea was expressed, while no such
      activity was detected in the extracts expressed with the dusky mutant cDNAs
      containing 4-bp insertions. Moreover, the introduced Ip3GGT cDNA efficiently
      produced 3GGT that converted cyanidin 3-O-glucoside into cyanidin 3-O-sophoroside
      in transgenic petunia plants.

PMID- 15842622
TI  - A secreted lipase of Fusarium graminearum is a virulence factor required for
      infection of cereals.
AB  - Fusarium graminearum is the causal agent of the Fusarium head blight (FHB) and a
      destructive pathogen of cereals accounting for high grain yield losses especially
      on wheat and maize. Like other fungal pathogens, F. graminearum secretes various
      extracellular enzymes, which are hypothesized to be involved in host infection.
      Extracellular lipolytic activity of F. graminearum was strongly induced in
      culture by wheat germ oil; this allowed us to isolate, clone, and characterize a
      gene (FGL1) encoding a secreted lipase. Expression analysis indicated that FGL1
      is induced by lipid-containing substrates and repressed by glucose. In planta,
      FGL1 transcription was detected 1 day post-infection of wheat spikes. The
      function of the FGL1 gene product was verified by specifically demonstrating
      lipase activity after expression in a heterologous host. Ebelactone B, a known
      lipase inhibitor, repressed the lipolytic activity of the enzyme. Disease
      severity was strongly reduced when wild-type conidia were supplemented with
      ebelactone B. Transformation-mediated disruption of FGL1 led to reduced
      extracellular lipolytic activity in culture and to reduced virulence to both
      wheat and maize.

PMID- 15842623
TI  - EDS1 in tomato is required for resistance mediated by TIR-class R genes and the
      receptor-like R gene Ve.
AB  - In tobacco and other Solanaceae species, the tobacco N gene confers resistance to
      tobacco mosaic virus (TMV), and leads to induction of standard defense and
      resistance responses. Here, we report the use of N-transgenic tomato to identify
      a fast-neutron mutant, sun1-1 (suppressor of N), that is defective in N-mediated
      resistance. Induction of salicylic acid (SA) and expression of pathogenesis
      related (PR) genes, each signatures of systemic acquired resistance, are both
      dramatically suppressed in sun1-1 plants after TMV treatment compared to wild
      type plants. Application of exogenous SA restores PR gene expression, indicating
      that SUN1 acts upstream of SA. Upon challenge with additional pathogens, we found
      that the sun1-1 mutation impairs resistance mediated by certain resistance (R)
      genes, (Bs4, I, and Ve), but not others (Mi-1). In addition, sun1-1 plants
      exhibit enhanced susceptibility to TMV, as well as to virulent pathogens. sun1-1
      has been identified as an EDS1 homolog present on chromosome 6 of tomato. The
      discovery of enhanced susceptibility in the sun1-1 (Le_eds1-1) mutant plant,
      which contrasts to reports in Nicotiana benthamiana using virus-induced gene
      silencing, provides evidence that the intersection of R gene-mediated pathways
      with general resistance pathways is conserved in a Solanaceous species. In
      tomato, EDS1 is important for mediating resistance to a broad range of pathogens
      (viral, bacterial, and fungal pathogens), yet shows specificity in the class of R
      genes that it affects (TIR-NBS-LRR as opposed to CC-NBS-LRR). In addition, a
      requirement for EDS1 for Ve-mediated resistance in tomato exposes that the
      receptor-like R gene class may also require EDS1.

PMID- 15842624
TI  - The pvr1 locus in Capsicum encodes a translation initiation factor eIF4E that
      interacts with Tobacco etch virus VPg.
AB  - Mutations in the eIF4E homolog encoded at the pvr1 locus in Capsicum result in
      broad-spectrum potyvirus resistance attributed to the pvr1 resistance allele, a
      gene widely deployed in agriculture for more than 50 years. We show that two
      other resistance genes, previously known to be eIF4E with narrower resistance
      spectra, pvr2(1) and pvr2(2), are alleles at the pvr1 locus. Based on these data
      and current nomenclature guidelines, we have re-designated these alleles, pvr1(1)
      and pvr1(2), respectively. Point mutations in pvr1, pvr1(1), and pvr1(2) grouped
      to similar regions of eIF4E and were predicted by protein homology models to
      cause conformational shifts in the encoded proteins. The avirulence determinant
      in this potyvirus system has previously been identified as VPg, therefore yeast
      two-hybrid and GST pull-down assays were carried out with proteins encoded by the
      pvr1 alleles and VPg from two different strains of Tobacco etch virus (TEV) that
      differentially infected Capsicum lines carrying these genes. While the protein
      encoded by the susceptible allele pvr1+ interacted strongly, proteins translated
      from all three resistance alleles (pvr1, pvr1(1), and pvr1(2)) failed to bind VPg
      from either strain of TEV. This failure to bind correlated with resistance or
      reduced susceptibility, suggesting that interruption of the interaction between
      VPg and this eIF4E paralog may be necessary, but is not sufficient for potyvirus
      resistance in vivo. Among the three resistance alleles, only the pvr1 gene
      product failed to bind m7-GTP cap-analog columns, suggesting that disrupted cap
      binding is not required for potyvirus resistance.

PMID- 15842625
TI  - SIPK signaling controls multiple components of harpin-induced cell death in
      tobacco.
AB  - Harpin from Pseudomonas syringae pv. phaseolicola (HrpZ) elicits a rapid cell
      death response in tobacco plants. Multiple signaling components, including
      mitogen-activated protein kinase (MAPK), reactive oxygen species (ROS) and
      salicylic acid (SA), have been reported to be involved in this cell death
      process, but the interaction between these molecules is poorly understood. Here
      we show through utilizing plants manipulated in SIPK expression levels that lack
      of SIPK results in increased sensitivity to harpin with concomitant accumulation
      of higher levels of ROS. Conversely, SIPK-overexpressing plants show reduced
      sensitivity to harpin relative to wild-type plants, and display reduced ROS
      accumulation. Harpin-induced cell death was found to be conditional on the
      ability of the plant to accumulate SA, whereas harpin induction of MAPK
      activation and ROS accumulation are not. However, harpin-induced ROS accumulation
      is required for activation of SIPK and wound-induced protein kinase.
      Transcriptional profiling revealed that suppression of SIPK signaling also
      affects early expression of a range of pathogen- and stress-responsive genes
      during harpin challenge.

PMID- 15842626
TI  - Staphylococcus aureus pathogenicity on Arabidopsis thaliana is mediated either by
      a direct effect of salicylic acid on the pathogen or by SA-dependent, NPR1
      independent host responses.
AB  - Staphylococcus aureus is a ubiquitous gram-positive bacterium that can cause
      superficial to serious systemic infections in animals and humans. Here we report
      the development of a plant infection model to study the pathogenesis of this
      bacterium. Three global regulatory mutants, RN6911 (agr-), ALC 488 (sarA-) ALC
      842 (sarA-/agr-) and an alpha-toxin mutant defective in biofilm formation
      (DU1090) which are attenuated in animal pathogenesis, were also attenuated in
      their ability to infect plants, suggesting that these regulators that mediate
      synthesis of virulence factors essential for animal pathogenesis are also
      required for plant pathogenesis. Further, using Arabidopsis plants altered in
      defense responses such as the transgenic lines NahG [defective in salicylic acid
      (SA) accumulation], and 35S-LOX2- (defective in jasmonic acid production and
      hyper-accumulator of SA), and mutants ics1 (depleted in SA accumulation), and
      npr1-1 (non-expressor of pathogenesis-related protein) we show that resistance of
      Arabidopsis to typical plant pathogens and the animal pathogen S. aureus is
      conserved and is mediated by SA. The data presented here suggest that Arabidopsis
      thaliana resistance to S. aureus is mediated either by a direct effect of SA on
      the pathogen, specifically one that affects the attachment/aggregate formation on
      the root surface and reduces the pathogen's virulence, or by SA-dependent, NPR1
      independent host responses.

PMID- 15842627
TI  - An essential function of phosphatidylinositol phosphates in activation of plant
      shaker-type K+ channels.
AB  - A prominent regulatory property of plant shaker-type K+ channels is the 'rundown'
      that causes channel closure upon membrane excision from the cell, implicating
      intracellular factor(s) in maintaining channel activity. One such factor has been
      identified as hydrolysable ATP-Mg although the mechanism for ATP function remains
      unknown. Here we report identification of phosphatidylinositol (PI) phosphates
      (PIPs) as essential regulators for the voltage-dependent and -independent
      activation of plant shaker-type channels such as SKOR, an outward rectifying K+
      channel. Inhibition of PI kinase activity abolished the function of ATP-Mg in
      restoration of rundown channel activity, demonstrating that PIPs production by PI
      kinases and ATP-Mg underlies ATP-induced activation of the rundown channel. We
      also identified aluminum block as a common feature of the plant shaker-type
      channels and provided evidence that aluminum block of these channels may result
      from Al interaction with PIPs.

PMID- 15842628
TI  - Marking cell lineages in living tissues.
AB  - We have generated a novel genetic system to visualize cell lineages in living
      tissues at high resolution. Heat shock was used to trigger the excision of a
      specific transposon and activation of a fluorescent marker gene. A histone-YFP
      marker was used to allow identification of cell lineages and easy counting of
      cells. Constitutive expression of a green fluorescent membrane protein was used
      to provide a precise outline of all surrounding cells. Marked lineages can be
      induced from specific cells within the organism by targeted laser irradiation,
      and the fate of the marked cells can be followed non-invasively. We have used the
      system to map cell lineages originating from the initials of primary and lateral
      roots in Arabidopsis. The lineage marking technique enabled us to measure the
      differential contribution of primary root pericycle cell files to developing
      lateral root primordia. The majority of cells in an emerging lateral root
      primordium derive from the central file of pericycle founder cells while off
      centre founder cells contribute only a minor proliferation of tissue near the
      base of the root. The system shows great promise for the detailed study of cell
      division during morphogenesis.

PMID- 15842629
TI  - Morphology of angiogenesis in human cancer: a conceptual overview,
      histoprognostic perspective and significance of neoangiogenesis.
AB  - This paper reviews the histomorphological aspects of angiogenesis and
      neoangiogenesis, quantitative and qualitative, and their applications in
      prognostic evaluation of neoplastic diseases. The merits and weak points of
      intratumoral microvessel density (MVD), a widely regarded bona fide predictor of
      tumour growth, metastases and patient survival, are discussed. Total
      microvascular area (TVA) has been found useful in recent prognostic studies
      utilizing newer immunohistochemical vascular markers. Of particular significance
      is the fact that MVD and TVA are most predictive of patient outcome in those
      tumours that induce significant neoangiogenesis, namely carcinomas of breast and
      prostate, and haematological malignancies. In contrast, carcinomas of lung and
      urinary bladder do not show significant associations of MVD and TVA with poor
      prognosis, reflecting differences in angiogenic mechanisms. In gliomas, MVD
      appears to correlate with outcome in high-grade, but not low-grade tumours, and
      does not correlate with tumour cellularity in the infiltrating portions of the
      tumour, reflecting a paucity of neoangiogenesis and directional vascular growth.
      Recent studies have found CD105, Tie-2/Tek and vascular endothelial growth factor
      receptors to be the best markers of neoangiogenesis. The vascular parameters so
      measured correlate better with overall and disease-free survival in breast, colon
      and lung carcinoma than panendothelial markers such as CD31. A correlation of
      vascular patterns with prognosis has been established in ocular melanomas,
      glioblastomas and squamous carcinomas of head and neck region. Vascular networks
      with closed loops are closely associated with mortality due to metastases in
      uveal melanomas. Fewer bizarre glomeruloid vessels and prominent classical
      capillary pattern was an independent predictor of longer survival in
      glioblastoma. Therefore a judicious combination of quantitative and qualitative
      microscopic angiogenic parameters, with emphasis on neoangiogenesis and vascular
      patterns wherever applicable, should be an integral component of a more
      consistent tumour staging system for accurate prognostic evaluation of tumours,
      selection of optimal anti-angiogenic therapy and pertinent research.

PMID- 15842630
TI  - Rheumatoid arthritis and pigmented villonodular synovitis: comparative analysis
      of cell polyploidy, cell cycle phases and expression of macrophage and fibroblast
      markers in proliferating synovial cells.
AB  - AIMS: Rheumatoid arthritis (RA) and pigmented villonodular synovitis (PVNS) are
      aggressive diseases with progressive joint destruction. The present study aims to
      define cell cycle phases, polyploidy and the immunophenotype of proliferating
      synovial cells in both diseases. METHODS AND RESULTS: Synovial tissues from
      patients with proliferative-active RA, localized and diffuse PVNS were analysed
      by DNA flow cytometry, immunohistochemistry and double immunofluorescence with
      confocal laser scan microscopy. Expression of macrophage markers (CD68/CD163),
      fibroblast markers (h4Ph/CD55) and Ki67 antigen was examined. Synovial cells
      positive for either macrophage or fibroblast markers as well as double-labelled
      cells were found in both RA and PVNS. In RA, CD68/CD163+ synoviocytes were
      preferentially located in the vicinity of the synovial lining layer, while they
      were more randomly distributed in PVNS. Of cases with diffuse PVNS, 20% showed an
      aneuploid cell pattern. All samples of localized PVNS and RA were diploid.
      Proliferative activity was significantly higher in aneuploid PVNS. CONCLUSIONS:
      In spite of their histologically homogeneous appearance, proliferating synovial
      cells display a heterogeneous immunophenotype in both RA and PVNS, indicating
      functional properties of both macrophages and fibroblasts. Aneuploidy seems to be
      a special feature of diffuse PVNS.

PMID- 15842631
TI  - Cutaneous clear cell myomelanocytic tumour: a new member of the growing family of
      perivascular epithelioid cell tumours (PEComas). Clinicopathological and
      immunohistochemical analysis of seven cases.
AB  - AIMS: To analyse seven cases of cutaneous myomelanocytic tumour histologically
      and immunohistochemically. Perivascular epithelioid cell tumours (so-called
      PEComas) are rare and recently delineated neoplasms occurring in the lung,
      kidney, pancreas, uterus, falciform ligament, vulva, heart, prostate and soft
      tissues. PEComas are characterized by a perivascular location of neoplastic cells
      showing a broad spectrum of epithelioid and spindled cells with clear, and
      granular pale eosinophilic cytoplasm, and a variable expression of melanocytic
      and muscle markers, whereas S100 protein and cytokeratins are usually absent.
      METHODS AND RESULTS: We report seven cases of cutaneous myomelanocytic tumour
      arising on the lower (six cases) and upper (one case) extremities of female
      adults (age range 30-66 years). In all cases an ill-defined dermal lesion with
      extension into subcutaneous tissue was noted. The neoplasms contained numerous
      blood vessels with a lace-like pattern and slightly thickened vessel walls, and
      were composed of perivascular epithelioid cells containing clear or focally
      granular pale eosinophilic cytoplasm and round vesicular nuclei with small,
      sometimes slightly enlarged nucleoli. Increased proliferative activity and tumour
      necrosis were not seen. Immunohistochemically, tumour cells stained positively
      for HMB-45, microphthalmia transcription factor, and NKIC3 in all cases, whereas
      perivascular expression of alpha-smooth muscle actin and focal positivity for
      desmin were noted in one case each only. Two out of four cases tested stained
      focally positive for calponin. No expression of S100 protein and pancytokeratin
      was present. Despite incomplete/marginal excision in three cases none of the
      neoplasms has recurred locally so far. CONCLUSIONS: With the presented series of
      cutaneous myomelanocytic tumours the clinicopathological spectrum of PEComas is
      expanded.

PMID- 15842632
TI  - Tissue microarray analysis of multiple gene expression in intestinal metaplasia,
      dysplasia and carcinoma of the stomach.
AB  - AIMS: To study multiple gene expression patterns and their roles in the process
      of gastric carcinogenesis. METHODS AND RESULTS: Using a high-throughput tissue
      microarray technique, 169 specimens from gastric carcinomas, precursor lesions
      and normal mucosa were immunostained on a series of tissue chips for p53,
      p21(WAF1/CIP1) cyclin E, Bcl-2, c-met and mucin 5AC expression. The
      overexpression of p53 was observed in 10.7% of low-grade dysplasia (LGD), 38.1%
      of high-grade dysplasia (HGD) and 39.6% of intestinal type gastric carcinoma
      (IGC). Expression of p21(WAF1/CIP1) was found in 47.6% of incomplete intestinal
      metaplasia (IM), 36.7% of dysplasia (Dys) and 29.5% of IGC. The overexpression of
      cyclin E was more frequently present in carcinomas than in Dys (P < 0.05);
      moreover, high-level expression (> 25% in extent) of cyclin E was observed only
      among IGC. Abnormal Bcl-2 expression was present in 81.0% of incomplete IM, 69.4%
      of Dys and 22.9% of IGC. Along with progression of the lesion, the expression of
      c-met increased; in contrast, mucin 5AC decreased gradually. CONCLUSIONS: The
      specific expression pattern in incomplete IM was mucin 5AC+/Bcl-2+/p53-/cyclin E
      , while mucin 5AC-/cyclin E+ was specific for IGC. p53 was useful for
      distinguishing LGD from HGD. High-level expression of cyclin E might be an
      indicator for malignant transformation of dysplasia.

PMID- 15842633
TI  - Characterization of macrophage subpopulations in colon cancer using tissue
      microarrays.
AB  - AIMS: To determine the pattern of macrophage infiltration in colon cancers and
      its correlation with clinicopathological characteristics. METHODS AND RESULTS:
      Colon cancers from 100 patients were arrayed into a tissue microarray (TMA). Four
      cores per tumour were taken: three from the invasion front (IF) and one from the
      tumour surface (TS). Macrophages were quantified by immunohistochemistry with
      antibodies to the PG-M1, KP-1, MRP8, MRP14 and MRP8/14 antigens. The number of
      macrophages was significantly higher in the TS cores than in the IF cores and
      both tumour sites showed a higher number of macrophages than the normal mucosa.
      The number of macrophages decreased in higher stage tumours. The different tumour
      associated macrophage (TAM) subpopulations were positively correlated with each
      other. CONCLUSIONS: The increased number of macrophages in cancers compared with
      normal colon mucosa indicates that macrophages are attracted to the tumour site.
      However, decreasing macrophages in higher stage colon cancers suggest that this
      attraction decreases with tumour progression.

PMID- 15842634
TI  - PDGFR expression in differential diagnosis between KIT-negative gastrointestinal
      stromal tumours and other primary soft-tissue tumours of the gastrointestinal
      tract.
AB  - AIMS: To investigate the value of platelet-derived growth factor receptors
      (PDGFRs) by immunohistochemistry in discriminating KIT-negative gastrointestinal
      stromal tumours (GISTs) from other soft-tissue neoplasms of the digestive tract.
      METHODS AND RESULTS: One-hundred and sixty-seven primary gastrointestinal
      mesenchymal tumours (125 GISTs, 15 intra-abdominal desmoids, 12 leiomyomas, eight
      leiomyosarcomas, three schwannomas, two solitary fibrous tumours, and one case
      each of inflammatory pseudotumour and fibroid polyp) were reclassified based on
      morphology and on the immunohistochemical panel recommended by the National
      Institutes of Health consensus on GIST. All cases were then tested with
      antibodies specific for PDGFR alpha and beta. Of 125 GISTs, 117 were KIT-positive
      (93.6%) and eight KIT-negative (6.4%). All the KIT-positive GISTs were negative
      for both PDGFRs, while all the eight KIT-negative GISTs expressed PDGFR-alpha,
      with two of them also coexpressing PDGFR-beta. Among the 42 non-GIST tumours,
      only a small percentage (26.6%) of desmoids immunostained for PDGFR-alpha, two of
      them coexpressing PDGFR-beta. CONCLUSIONS: Immunostaining with PDGFR-alpha is a
      helpful marker in discriminating between KIT-negative GISTs and other
      gastrointestinal mesenchymal lesions: all KIT-negative GISTs were positive for
      PDFGR-alpha, while none of the other gastrointestinal mesenchymal tumours
      analysed, except a small subset of desmoids, was reactive with anti-PDGFRs. These
      preliminary data demonstrate the suitability of commercially available antibodies
      to detect immunohistochemically the mutually exclusive expression of KIT and
      PDGFR-alpha previously reported in GISTs by molecular biological techniques.
      Since PDGFR exists in the form of a homodimer (alphaalpha, betabeta) or
      heterodimer (alphabeta) and two of the KIT-negative GISTs coexpressed both PDGFR
      isoforms, further investigations are required to elucidate the role of PDGFR-beta
      in GISTs.

PMID- 15842635
TI  - Overexpression of anti-apoptotic Mcl-1 in testicular germ cell tumours.
AB  - AIMS: To determine the expression of Mcl-1 in testicular germ cell tumours in
      order to clarify the role of this anti-apoptotic factor in these tumours. Various
      members of the Bcl-2 family have been implicated in the apoptotic mechanisms
      regulating germ cell apoptosis. Mcl-1 is an anti-apoptotic Bcl-2 family member
      and has recently been reported to be related to the progression of malignancy;
      however, the involvement of Mcl-1 in the development of germ cell tumours is
      still unknown. METHODS AND RESULTS: Mcl-1 expression in testicular germ cell
      tumours was investigated by immunohistochemistry and reverse transcriptase
      polymerase chain reaction (RT-PCR). By immunohistochemistry, overexpression of
      Mcl-1 was present in all germ cell tumours that were studied, including embryonal
      carcinoma and yolk sac tumour, as well as choriocarcinoma and teratoma. In
      teratomas, Mcl-1 was widely distributed in the epithelial, myogenic, neural and
      mesenchymal components. RT-PCR analysis after microdissection revealed high
      levels of Mcl-1 mRNA in all tumour variants compared with non-neoplastic germ
      cells. CONCLUSION: Overexpression of anti-apoptotic Mcl-1 may function to enhance
      the viability of testicular germ cells, thereby leading to tumorigenesis.

PMID- 15842636
TI  - Bone marrow changes in chronic myelogenous leukaemia after long-term treatment
      with the tyrosine kinase inhibitor STI571: an immunohistochemical study on 75
      patients.
AB  - AIMS: To carry out an immunohistochemical study on bone marrow (BM) biopsy
      specimens in 75 patients with chronic myelogenous leukaemia (CML) on long-term
      STI571 therapy. METHODS AND RESULTS: Sequential BM specimens taken at intervals
      of 21 +/- 6 months were investigated by enzyme- and immunohistochemistry
      including proliferating cell nuclear antigen and apoptosis. Evaluation was
      performed either by semiquantitative scoring or by morphometry (CD61+
      megakaryopoiesis). In 41 patients with chronic phase CML, treatment resulted in a
      significant decrease in cellularity and neutrophil granulopoiesis contrasting
      with an accumulation of erythroid precursor cells. Morphometry showed a reduction
      of abnormal micromegakaryocytes consistent with normalization. Regression of
      myelofibrosis was identified in eight of 15 patients, whereas progression
      occurred in 17 patients; mostly in those with acceleration and blastic crisis.
      The increased post-treatment incidence of reactive lymphoid nodules was
      remarkable. Myeloblasts, CD34+ progenitors and immature myelomonocytic cells
      initially decreased, but recurred in 14 patients who later developed a relapse.
      STI571 exerted an inhibitory effect on cell proliferation associated with
      enhanced apoptosis in responding patients. CONCLUSION: Long-term treatment with
      STI571 exerts pronounced changes on BM histopathology that not only involve
      haematopoiesis and stromal constituents, but also proliferation and apoptosis.

PMID- 15842637
TI  - Expression of claudins 1, 2, 3, 4, 5 and 7 in various types of tumours.
AB  - AIMS: Claudins are adhesion molecules present in tight junctions. To evaluate
      their usefulness as differentiation markers claudins 1, 2, 3, 4, 5 and 7 were
      studied in 116 epithelial and 92 non-epithelial tumours. METHODS AND RESULTS:
      Immunoreactivity for all claudins could be seen in different carcinomas. There
      were, however, tumour type-specific differences in their expression. Lower
      expression of claudin 2 was seen in breast and prostatic carcinomas, while
      hepatocellular and renal carcinomas expressed lower levels of claudins 4 and 5.
      In contrast to epithelial tumours, lymphomas did not express claudins and most
      soft tissue tumours and naevocytic lesions were negative or showed weaker, mainly
      cytoplasmic positivity for some claudins. Of non-epithelial tumours, claudin 5
      was found only in angiosarcomas and benign vascular tumours, which also showed
      reactivity for claudins 2, 3 and 7, but was not expressed in any other soft
      tissue lesions or lymphomas. CONCLUSIONS: The results show that claudins 1, 2, 3,
      4, 5 and 7 can be used as markers for epithelial differentiation and to
      distinguish epithelial neoplasms from lymphomas and selectively also from soft
      tissue and naevocytic lesions. Since these claudins show type-specific
      differential expression in epithelial tumours, they may also be of some value in
      distinguishing different epithelial tumours from each other. Additionally,
      claudin 5 shows promise as a marker for endothelial lesions compared with other
      soft tissue lesions.

PMID- 15842638
TI  - COX-2 expression in DCIS: correlation with VEGF, HER-2/neu, prognostic molecular
      markers and clinicopathological features.
AB  - AIMS: There is considerable evidence that links COX-2 to the development of
      cancer. The aim of our study was to assess, by immunohistochemistry, COX-2
      expression in ductal carcinoma in situ (DCIS) and its possible correlation with
      HER-2/neu, vascular endothelial growth factor (VEGF) expression and other common
      immunohistochemical parameters (p53, ER, PGR, Ki67). METHODS AND RESULTS: Tissue
      samples of 49 archival cases of DCIS without any invasive component were analysed
      for COX-2, HER-2/neu, VEGF, oestrogen and progesterone receptors, Ki67 and p53 by
      immunohistochemistry using specific antibodies. COX-2 expression was detected in
      43 (87.8%) tissue samples, of which 12 (24.5%) were graded as weak, 22 (44.9%) as
      moderate and nine (8.4%) as high expression. Only six (12.2%) lesions were
      negative for COX-2 expression. VEGF expression was detected in 93.8% of samples;
      66.7% of lesions were found to be positive for HER-2/neu expression. Furthermore,
      COX-2 expression was significantly correlated with VEGF expression (P = 0.003). A
      significant positive correlation was also observed between COX-2 and HER-2/neu
      expression (P < 0.0001). CONCLUSIONS: Our results suggest that COX-2 is highly
      expressed in DCIS and takes part in the molecular pathway implicated in
      progression of breast cancer and may provide a rationale for targeting COX-2 in
      preinvasive breast cancer therapy.

PMID- 15842639
TI  - Expression of S100A2 and S100A6 in thyroid carcinomas.
AB  - AIMS: S100 calcium-binding proteins are known to play multiple roles in carcinoma
      development. In this study, we focused on two kinds of these proteins, S100A2 and
      S100A6, and investigated their expression in thyroid neoplasms. METHODS AND
      RESULTS: We investigated S100A2 and S100A6 expression in 141 thyroid neoplasms by
      immunohistochemistry. S100A2 was not expressed in normal follicles or follicular
      tumours, with one exception. Although 89.5% of papillary carcinoma were positive
      for S100A2, the expression was heterogeneous except in two cases. In anaplastic
      carcinoma, 78.5% of cases expressed S100A2 diffusely, while the remaining cases
      were negative. In normal follicles, S100A6 expression was always low, while 8.3%
      of follicular adenomas and 39.5% of follicular carcinomas showed increased
      expression. In papillary carcinomas, S100A6 expression was increased in 75% of
      cases, but in anaplastic carcinomas it was decreased, with only 14.3% showing
      high expression. CONCLUSIONS: The expression patterns of S100A2 and S100A6 in
      thyroid neoplasms are unique compared with those of other carcinomas, suggesting
      that: (i) S100A2 and S100A6 contribute to certain events in papillary carcinoma
      progression, and (ii) S100A2 expression is one of the biological characteristics
      of anaplastic carcinoma.

PMID- 15842640
TI  - Nuclear expression of maspin is associated with a lower recurrence rate and a
      longer disease-free interval after surgery for squamous cell carcinoma of the
      larynx.
AB  - AIMS: Maspin, a protein belonging to the serpin superfamily, is the product of a
      tumour suppressor gene. Tissue distribution studies have shown maspin expression
      in normal mammary epithelial cells, in the placenta, prostate, thymus, testis,
      oral cavity, small intestine, skin, and cornea. Maspin is expressed but down
      regulated in human breast, prostatic, and colonic cancers but apparently up
      regulated in pancreatic, ovarian, and gastric cancers. Only two studies
      concerning maspin expression in head and neck carcinomas are available. The
      present study is the first attempt to determine maspin expression in laryngeal
      carcinoma. METHODS AND RESULTS: Maspin expression was evaluated in 21 cases of
      laryngeal carcinoma consecutively treated with an exclusively surgical approach
      with a follow-up period longer than 24 months. The expression of p53, p27 and MIB
      1 was also studied. Two patterns of distribution of maspin in laryngeal
      neoplastic cells were found. Cytoplasmic expression of maspin was identified in
      47.6% of the cases. Nuclear maspin positivity was determined in 47.6% of the
      cases. A statistically significant difference in nuclear maspin expression
      between the group of patients without carcinoma recurrence and the group with
      evidence of recurrence was demonstrated (P = 0.039). Log rank test analysis
      showed a statistically significant direct correlation between nuclear maspin
      expression and disease-free intervals after surgical treatment calculated in
      months (P = 0.028). A significant inverse correlation was disclosed between
      nuclear maspin staining and MIB-1 (P = 0.028). A trend of increasing p27
      expression was noted in cases with positive nuclear maspin expression. Nuclear
      maspin expression was not statistically correlated with p53 expression. A trend
      towards direct correlation between cytoplasmic maspin expression and squamous
      cell carcinoma histological grade (G) was apparent. Cytoplasmic maspin expression
      did not correlate with p53, MIB-1 or p27 expression. CONCLUSIONS: These
      preliminary results suggest that nuclear location of maspin is a good prognostic
      factor in laryngeal carcinoma.

PMID- 15842641
TI  - Cervical ectopic thymoma: a diagnostic pitfall on frozen section.

PMID- 15842643
TI  - Breast carcinoma metastatic to follicular adenoma of the thyroid gland.

PMID- 15842644
TI  - Papillary serous carcinoma of ovarian type of the testis with borderline
      differentiation.

PMID- 15842645
TI  - A malignant hepatic tumour with osteoclast-like giant cells.

PMID- 15842646
TI  - Schwannoma with focal smooth muscle differentiation: a potential pitfall in the
      interpretation of core biopsies.

PMID- 15842648
TI  - Myometrial leiomyoma with chondroid lipoma-like areas.

PMID- 15842647
TI  - Inguinal dedifferentiated liposarcoma with meningothelial-like whorls and
      metaplastic bone formation.

PMID- 15842649
TI  - Dieulafoy's disease of the bronchus: an uncommon entity.

PMID- 15842651
TI  - Drug-induced haemolysis and methaemoglobinaemia in glucose 6-phosphate
      dehydrogenase deficiency.

PMID- 15842652
TI  - Transfusion-related acute lung injury.

PMID- 15842653
TI  - Pregnancy and its management in the Philadelphia negative myeloproliferative
      diseases.
AB  - The myeloproliferative diseases (MPDs) present several therapeutic challenges in
      patients of childbearing potential. The most extensive literature exists for
      patients with essential thrombocythaemia, with over 200 pregnancies reported in
      retrospective case series. Yet there is conflicting data in relation to
      predicting pregnancy outcome and optimal management strategy. Pregnancy is less
      frequently reported for polycythaemia vera and myelofibrosis. There is a need for
      collaboration to further our knowledge in this field. Here, the literature is
      reviewed in detail and experience of different therapeutic strategies in
      pregnancy discussed. There is increasing understanding about the pathogenesis of
      placental dysfunction in inherited thrombophilia and antiphospholipid antibody
      syndrome pregnancy outcomes in these conditions parallel those reported for MPDs.
      Furthermore several large studies have influenced pregnancy management in these
      conditions and, whilst not directly applicable to MPDs, this data have potential
      to inform treatment protocols. This data are reviewed and a personal management
      strategy for pregnancy in MPD proposed.

PMID- 15842654
TI  - Molecular mechanisms of fibrinolysis.
AB  - The molecular mechanisms that finely co-ordinate fibrin formation and
      fibrinolysis are now well defined. The structure and function of all major
      fibrinolytic proteins, which include serine proteases, their inhibitors,
      activators and receptors, have been characterized. Measurements of real time,
      dynamic molecular interactions during fibrinolysis of whole blood clots can now
      be carried out in vitro. The development of gene-targeted mice deficient in one
      or more fibrinolytic protein(s) has demonstrated expected and unexpected roles
      for these proteins in both intravascular and extravascular settings. In addition,
      genetic analysis of human deficiency syndromes has revealed specific mutations
      that result in human disorders that are reflective of either fibrinolytic
      deficiency or excess. Elucidation of the fine control of fibrinolysis under
      different physiological and pathological haemostatic states will undoubtedly lead
      to novel therapeutic interventions. Here, we review the fundamental features of
      intravascular plasmin generation, and consider the major clinical syndromes
      resulting from abnormalities in fibrinolysis.

PMID- 15842655
TI  - Killing of non-Hodgkin lymphoma cells by autologous CD19 engineered T cells.
AB  - Adoptive immunotherapy with tumour-specific T cells is an emerging technology
      that may be applicable to a broad range of cancers. However, tumours can avoid T
      cell-mediated attack through multiple mechanisms including downregulation of
      major histocompatability complex (MHC). Consequently, engineering T cells to
      target intact protein antigen directly, thus bypassing the need for MHC
      presentation, can facilitate T cell targeting of tumour cells. Peripheral blood
      lymphocytes from nine of nine patients with non-Hodgkin lymphoma (NHL) were
      successfully gene-modified to express a receptor consisting of a CD19 single
      chain variable fragment (scFv) fused to the T cell CD3zeta signalling molecule.
      These T cells were functionally active against the CD19(+) Raji Burkitt's
      lymphoma cell line. Importantly, engineered T cells from seven of nine NHL
      patients efficiently lysed autologous lymph node tumour biopsy cells. There was a
      clear correlation between levels of CD19 expression on the tumour and effective
      killing by the engineered T cells. For two patients with a low or absent CD19(+)
      cells within the biopsy, no significant killing was observed. These results
      demonstrate that patients with CD19(+) NHL would be suitable candidates for this
      form of therapy in the setting of a phase I clinical trial.

PMID- 15842656
TI  - Somatic PTPN11 mutations in childhood acute myeloid leukaemia.
AB  - Somatic mutations in PTPN11, the gene encoding the transducer SHP-2, have emerged
      as a novel class of lesions that upregulate RAS signalling and contribute to
      leukaemogenesis. In a recent study of 69 children and adolescents with de novo
      acute myeloid leukaemia (AML), we documented a non-random distribution of PTPN11
      mutations among French-American-British (FAB) subtypes. Lesions were restricted
      to FAB-M5 cases, where they were relatively common (four of 12 cases). Here, we
      report on the results of a molecular screening performed on 181 additional
      unselected patients, enrolled in participating institutions of the Associazione
      Italiana Ematologia Oncologia Pediatrica-AML Study Group, to provide a more
      accurate picture of the prevalence, spectrum and distribution of PTPN11 mutations
      in childhood AML and to investigate their clinical relevance. We concluded that
      PTPN11 defects do not represent a frequent event in this heterogeneous group of
      malignancies (4.4%), although they recur in a considerable percentage of patients
      with FAB-M5 (18%). PTPN11 lesions rarely occur in other subtypes. Within the FAB
      M5 group no clear association of PTPN11 mutations with any clinical variable was
      evident. Nearly two third of the patients with this subtype were found to harbour
      an activating mutation in PTPN11, NRAS, KRAS2 or FLT3.

PMID- 15842657
TI  - Fusion hybrids of dendritic cells and autologous myeloid blasts as a potential
      cellular vaccine for acute myeloid leukaemia.
AB  - We assessed the potential of tumour cell/dendritic cell fusion hybrids to
      generate in vitro anti-leukaemic T-cell responses following co-culture with
      autologous remission lymphocytes in six patients with acute myeloid leukaemia
      (AML). Comparison was made to anti-leukaemic responses induced by mature
      dendritic cells (mDC) co-cultured with autologous, irradiated myeloid blasts.
      Fusion hybrids induced anti-leukaemic T-cell immune responses in three of six
      patients. Tumour-pulsed mDC induced T-cellular responses in two other patients.
      Only one of six patients remission lymphocytes failed to develop leukaemia
      directed immune responses following stimulation with either construct. Anti
      proliferative properties of fusion hybrids against allogeneic lymphocytes were
      observed in mixed lymphocyte-leukaemia reactions and were found not to be
      specific to the cell fusion partners and did not prevent the ability of AML-mDC
      heterokaryons to induce autologous anti-leukaemic cytotoxicity. We conclude that
      tumour cell/dendritic cell fusion hybrids hold promise as a cellular vaccine for
      AML.

PMID- 15842658
TI  - Prognosis of patients with acute myeloid leukaemia admitted to intensive care.
AB  - This retrospective study assessed the prognostic factors associated with early
      and long-term outcome in consecutive patients with acute myeloid leukaemia (AML)
      admitted to the intensive care unit (ICU) over a 9-year period. A total of 83
      patients were studied (age 48 +/- 16 years), among whom 60% were neutropenic on
      admission. For 68%, admission occurred within the first month following diagnosis
      of AML. The main reason for ICU admission was an acute respiratory disease in 82%
      of cases. Mechanical ventilation (MV) was required in 57% of patients. In-ICU
      mortality was 34%. Among patients discharged alive from ICU, 49% died within a
      year after discharge. Factors significantly associated with in-ICU death in
      multivariate analysis were simplified acute physiology score II and need for
      invasive MV (IMV). Age, performance status, AML3 subtype and complete remission
      were significantly associated with 1-year survival. Patients with acute
      respiratory failure initially supported with non-invasive MV had significantly
      better ICU outcome than patients initially supported with IMV. In conclusion, ICU
      admission is justified for selected patients with AML. The ICU mortality rate is
      highly predictable by the acute illness severity score. A 1-year survival is
      predicted by haematological prognostic factors.

PMID- 15842659
TI  - Haplotypes in the tumour necrosis factor region and myeloma.
AB  - This study described the haplotypic structure across a region of chromosome 6
      including the tumour necrosis factor (TNF) gene, and investigated its influence
      on the aetiology of myeloma. A total of 181 myeloma cases from the Medical
      Research Council Myeloma VII trial and 233 controls from the Leukaemia Research
      Fund Case Control Study of Adult Acute Leukaemia were included in the analysis.
      Genotyping by induced heteroduplex generator analysis was carried out for single
      nucleotide polymorphisms (SNP) located at positions -1031, -863, -857, -308 and 
      238 of the 5' promoter region of TNF-alpha gene, and 252 in the LT-alpha gene;
      and five microsatellites, TNFa, b, c, d and e. Haplotypes were inferred
      statistically using the phase algorithm. A limited diversity of haplotypes was
      observed, with the majority of variation described by 12 frequent haplotypes.
      Detailed characterization of the haplotype did not provide greater determination
      of disease risk beyond that described by the TNF-alpha-308 SNP. Some evidence was
      provided for a decreased risk of myeloma associated with the TNF-alpha-308
      variant allele A, odds ratio, 0.57; 95% confidence interval, 0.38-0.86. The
      results of this study did not support our starting hypothesis; that high producer
      haplotypes at the TNF locus are associated with an increased risk of developing
      myeloma.

PMID- 15842660
TI  - The International Prognostic Index determines the outcome of patients with nodal
      mature T-cell lymphomas.
AB  - The World Health Organization (WHO) lymphoma classification recognises anaplastic
      large cell lymphoma (ALCL), angioimmunoblastic lymphoma (AIL) and peripheral T
      cell lymphoma, unspecified (PTCU) as nodal mature T-cell lymphomas. Little is
      known about long-term outcome and prognostic factors of these diseases. A
      retrospective analysis on 125 patients with ALCL, AIL or PTCU was performed to
      evaluate outcome parameters, taking into account histological subtype and the
      International Prognostic Index (IPI). Median age was 54 years (range 17-90
      years). Complete remission (CR) was achieved in 51% of patients. Five-year
      overall survival (OS) was 43%, and 5-year relapse-free survival was 69%. Five
      year OS was 61% for ALCL, 45% for PTCU and 28% for AIL. With regard to the IPI, 5
      year OS was 74%, 49%, 21% and 6% for the low, low-intermediate, high-intermediate
      and high risk groups, respectively. In the multivariate analysis, the IPI but not
      the histological subtype significantly predicted survival. To a large extent, the
      IPI score explains the differences in survival between histological subtypes of
      nodal mature T-cell lymphomas. The IPI may therefore be used for risk
      stratification in clinical trials to identify patients who would benefit most
      from new treatment strategies, such as high-dose chemotherapy followed by stem
      cell or bone marrow transplantation.

PMID- 15842661
TI  - Aberrant somatic hypermutation and expression of activation-induced cytidine
      deaminase mRNA in mediastinal large B-cell lymphoma.
AB  - To determine the possible role of aberrant somatic hypermutation (ASHM) and
      activation-induced cytidine deaminase (AID) expression in the pathogenesis of
      mediastinal large B-cell lymphoma (MBL), the mutational status of genes affected
      by ASHM, including c-MYC, PAX-5 and RhoH, was analysed, and the expression level
      of AID mRNA in tumour specimens from six patients with MBL was determined.
      Mutations in one or more genes and high expression of AID mRNA were detected in
      all the six cases of MBL. These results suggest that ASHM and AID expression may
      have a role in the pathogenesis of MBL.

PMID- 15842662
TI  - Targeting primary human leukaemia cells with RNA interference: Bcr-Abl targeting
      inhibits myeloid progenitor self-renewal in chronic myeloid leukaemia cells.
AB  - We have investigated functional outcome of challenging primary chronic myeloid
      leukaemia (CML) cells with Bcr-Abl fusion sequence-directed RNA interference
      (RNAi). We targeted the Bcr-Abl b3a2 variant, by RNAi, in primary chronic phase
      CML cells, and detected strikingly reduced proliferation of myeloid precursor
      cells expressing this variant. Lack of an effect in cells expressing a distinct
      Bcr-Abl variant confirmed the specificity of the response. Through the functional
      targeting of an oncogene in primary human tumour cells, we have demonstrated that
      Bcr-Abl enhances CML progenitor cell amplification, and that RNAi may be suitable
      for development as a specific anti-leukaemia treatment.

PMID- 15842663
TI  - Prognostic relevance of 'early-onset' graft-versus-host disease following non
      myeloablative haematopoietic cell transplantation.
AB  - We retrospectively analysed outcomes among 395 patients with haematologic
      malignancies who underwent non-myeloablative haematopoietic cell transplantation
      (HCT) from human leucocyte antigen (HLA)-matched related (n = 297) or unrelated
      donors (n = 98) in order to identify a possible correlation between the time of
      onset of graft-versus-host disease (GVHD) and survival. The non-myeloablative
      regimen consisted of 2 Gy total body irradiation with or without fludarabine,
      followed by postgrafting immunosuppression with mycophenolate mofetil and
      cyclosporine. The cumulative incidences of grades II-IV acute GVHD and extensive
      chronic GVHD were 45% and 47%, respectively, with related donors, and 68% and
      68%, respectively, with unrelated donors. High-dose corticosteroid treatment for
      acute or chronic GVHD was started at a median of 79 (range, 8-799) days and 30
      (range, 5-333) days after transplantation from related and unrelated donors
      respectively. With related donors, the cumulative incidence of non-relapse
      mortality among patients with GVHD was 55% at 4 years when prednisone was started
      before day 50 (n = 72), compared with 29% when treatment was started after day 50
      (n = 115) (P < 0.001). With unrelated donors, time to onset of treatment for GVHD
      was not associated with survival. Patients with early-onset GVHD after non
      myeloablative HCT from HLA-identical related donors might benefit from
      intensified primary immunosuppressive treatment.

PMID- 15842664
TI  - UTY-specific TCR-transfer generates potential graft-versus-leukaemia effector T
      cells.
AB  - Immunotherapeutic approaches that target antigens that are differentially
      recognized on haematopoietic and non-haematopoietic cells may specifically
      enhance the graft-versus-leukaemia (GVL) effect of donor lymphocyte infusion. In
      this study, we have characterized a new HLA-B*5201-restricted epitope of the UTY
      gene. Unusually, presentation of this epitope was restricted to lymphoblasts. As
      a result, a T cell clone specific to this epitope recognized normal and malignant
      male B and T lymphoblasts, while showing little reactivity towards male HLA
      B*5201+ fibroblasts. Transfer of its T cell receptor (TCR) into donor T cells led
      to the generation of large numbers of T cells, which acquired the specificity of
      the original clone, its avidity and the differential pattern of reactivity
      towards lymphoblasts and fibroblasts. Remarkably, the specific response of TCR
      transferred T cells was significantly higher than that of the original clone.
      This is the first demonstration of the possibility to preserve the specific
      pattern of a T cell response to a differentially expressed antigen after TCR
      transfer and to augment the amplitude of this response concomitantly. These
      results indicate that it may be feasible to enhance the GVL effect of donor
      lymphocyte infusions in lymphoproliferative malignancies by the transfer of TCRs
      specific to epitopes that are differentially recognized on lymphoblasts.

PMID- 15842665
TI  - One versus two high-dose cytarabine-based consolidation before autologous stem
      cell transplantation for young acute myeloblastic leukaemia patients in first
      complete remission.
AB  - We report on a randomized trial aimed to determine the impact of a second
      consolidative high-dose cytarabine-based chemotherapy (HiDAC) in patients with
      acute myeloid leukaemia prior to an autologous stem cell transplantation (ASCT).
      Patients aged 18-60 years, in complete remission (CR) received a first
      consolidation with daunorubicin and cytarabine at reduced dose. Patients not
      allocated to allogeneic transplantation received one course of HiDAC and then
      were randomized to receive an ASCT immediately (HiDAC 1 group) or after one more
      course of HiDAC (HiDAC 2 group). Out of the 437 initial patients, 351 achieved CR
      (80%), of those 277 (79%) were eligible for first HiDAC, and 128 (36%) were
      randomized (HiDAC 1:65, HiDAC 2:63). Overall survival, leukaemia-free survival
      and cumulative incidence of relapse and non-relapse deaths were 41% and 53% (P =
      0.14), 39% and 48% (P = 0.12), 57% and 47% (P = 0.11), 8% and 8% (P = 0.95) for
      HiDAC 1 and HiDAC 2 groups, respectively. Further studies are warranted with a
      larger number of patients to test the place of a second course of HiDAC in this
      setting.

PMID- 15842666
TI  - Efficient identification of T-cell clones associated with graft-versus-host
      disease in target tissue allows for subsequent detection in peripheral blood.
AB  - Graft-versus-host disease (GVHD) causes severe morbidity and mortality in
      allogeneic haematopoietic stem cell transplantation (HSCT) because of destruction
      of recipient tissues by donor alloreactive T cells. We hypothesized that GVHD
      specific T-cell clones are expanded within affected tissue of HSCT patients and
      can also be detected in blood at the time of active disease. A multiplex
      polymerase chain reaction (PCR) was used to amplify T-cell receptor (TCR)
      variable beta (VB) chain rearrangements in skin biopsies from eight allogeneic
      HSCT patients. Molecular analysis of the complementarity-determining region 3
      (CDR3) of amplified products defined expanded, potentially disease-associated
      'clonotypes' and enabled the design of clonotype-specific PCR assays. We detected
      immunodominant clones in seven of eight GVHD-positive skin biopsies. In serial
      skin biopsies from the same patient, the identical clone was found in each
      biopsy. In a patient who underwent two successive HSCTs from different donors,
      distinct clones were identified for each engraftment. Using clonotypic PCR
      assays, individual tissue-derived clones could be identified in peripheral blood
      samples obtained during active GVHD. We hypothesize that clonotypic sequences
      derived from target tissue can serve as markers for GVHD and may have utility in
      diagnosis and monitoring response to therapy, as well as enable future therapies
      targeted against pathogenic clones.

PMID- 15842667
TI  - Resolving and classifying haematopoietic bone-marrow cell populations by multi
      dimensional analysis of flow-cytometry data.
AB  - The study of normal or malignant haematopoiesis requires the analysis of
      heterogeneous cell populations using multiple morphological and molecular
      criteria. Flow cytometry has the capacity to acquire multi-parameter information
      of large haematopoietic cell populations, utilizing various combinations of >200
      molecular markers (clusters of differentiation, CD). However, current flow
      cytometry analyses are based on serial gating of two-parametric scatter plots--a
      process that is inherently incapable to discriminate all subgroups of cells in
      the data. Here we studied the cellular diversity of normal bone marrows (BM)
      using multi-dimensional cluster analysis of six-parametric flow cytometry data
      (four CD, forward scatter and side scatter), focusing mainly on the myeloid
      lineage. Twenty-three subclasses of cells were resolved, many of them inseparable
      even when examined in all possible two-parametric scatter plots. The multi
      dimensional analysis could distinguish the haematopoietic progenitors according
      to International Society of Haematotherapy and Graft Engineering criteria from
      other types of immature cells. Based on the defined clusters, we designed a
      classifier that assigns BM cells in samples to subclasses based on robust six
      dimensional position and extended shape. The analysis presented here can manage
      successfully both the increasing numbers of haematopoietic cellular markers and
      sample heterogeneity. This should enhance the ability to study normal
      haematopoiesis, and to identify and monitor haematopoietic disorders.

PMID- 15842668
TI  - Identification of DKC1 gene mutations in Japanese patients with X-linked
      dyskeratosis congenita.
AB  - Dyskeratosis congenita (DC) is a rare inherited multisystem disorder
      characterized by the triad of abnormal skin pigmentation, nail dystrophy and
      mucosal leucoplakia. X-linked recessive inheritances are recognized in
      approximately 40% of the patients. DKC1 has been identified as the gene
      responsible for X-linked DC, and genetic analyses have been performed in a
      worldwide study. Here, we performed genetic analysis of five Japanese patients
      with presumed X-linked DC, and identified four mutations in the DKC1 gene,
      including two novel missense mutations (Q31K and T357A). Such genetic analysis is
      useful for the definite diagnosis and genetic counselling of patients.

PMID- 15842669
TI  - Chronic oxidative stress reduces the respiratory burst response of neutrophils
      from beta-thalassaemia patients.
AB  - Beta-thalassaemia patients are susceptible to infections by mechanisms that are
      not fully understood. Polymorphonuclear neutrophils (PMN) destroy microbes by
      producing a burst of reactive oxygen species (ROS) (respiratory burst) in
      response to bacterial components, as well as to phorbol-myristate-acetate (PMA).
      In the present study, we compared ROS generation by normal and beta-thalassaemia
      PMN and assessed their response to PMA. Blood cells were subjected to gelatin
      separation, staining with dichlorofluorescin-diacetate and flow cytometry. At
      basal level, the fluorescence (mean fluorescence channel) of normal and
      thalassaemia PMN were 12.7 +/- 4.5 and 95.6 +/- 19.8 respectively; it changed to
      283.4 +/- 72.5 and 39.5 +/- 14.3, respectively, upon PMA stimulation, indicating
      that thalassaemia PMN have a higher basal ROS but a reduced response to PMA. When
      normal PMN were treated with the oxidants hydrogen peroxide and butyl
      hydroxyperoxide, as well as iron and haemin, which are elevated in thalassaemia,
      their basal ROS increased 5-22-fold, but the PMA response was abolished. Treating
      thalassaemic PMN with antioxidants (N-acetyl-L-cysteine or vitamins C and E)
      reduced their basal ROS but enhanced their PMA response. Our findings indicate
      that chronically stressed PMN, e.g. in thalassaemia, have reduced capacity to
      elicit a respiratory burst, which may compromise their antibacterial capacity,
      and imply prophylactic treatment with antioxidants for recurrent infections.

PMID- 15842670
TI  - Coombs' negative haemolytic anaemia as a first manifestation of autoimmune
      lymphoproliferative disease.

PMID- 15842671
TI  - Microchimerism detection by human leucocyte antigen-specific quantitative
      polymerase chain reaction analysis in recipients of allogeneic Epstein-Barr virus
      specific cytotoxic T lymphocytes.

PMID- 15842672
TI  - All-trans retinoic acid induced cardiac and skeletal myositis in induction
      therapy of acute promyelocytic leukaemia.

PMID- 15842673
TI  - 'Leukaemic' presentation of metastatic Merkel cell carcinoma.

PMID- 15842675
TI  - The long case revisited.

PMID- 15842676
TI  - Dither: indecisive agitation.

PMID- 15842677
TI  - More than doctors' communication skills.

PMID- 15842678
TI  - Characteristics of doctors and nurses as perceived by students entering medical
      school: implications for shared teaching.
AB  - INTRODUCTION: Debate continues with respect to when to introduce
      interprofessional education for maximal potential benefit. One perspective is
      that interprofessional education should be introduced early in the undergraduate
      curriculum before students develop stereotyped impressions of other professional
      groups. However, it may be that students at entry to medical school have already
      developed these stereotypical impressions. This study examines perceived
      professional characteristics of doctors and nurses by students entering medical
      school. METHODOLOGY: Year 1 medical students in 4 consecutive years completed a
      questionnaire on their perceptions of the characteristics and backgrounds of
      nurses and doctors and on their attitudes to shared teaching. RESULTS: Year 1
      medical students were found to perceive the characteristics of doctors and nurses
      differently. They considered nurses to be more caring and doctors to be more
      arrogant. They considered nurses to have lower academic ability, competence and
      status, although comparable life experience. They were generally very positive
      about beginning shared learning at an early stage of training. DISCUSSION: Whilst
      it is encouraging that medical students are positive about shared teaching, it is
      of concern that they have a poor perception of the academic ability, status in
      society and professional competence of the nurse at entry to medical school.
      These perceived impressions, which may reflect societal misconceptions regarding
      the roles and responsibilities of nurses within a modern health care system, may
      have an impact on the success of early interprofessional teaching initiatives in
      undergraduate curricula.

PMID- 15842679
TI  - The case for educating health care students in professionalism as the core
      content of interprofessional education.
AB  - BACKGROUND: Professional teams are becoming more central to health care as
      evidence emerges that effective teamwork enhances the quality of patient care.
      Currently, health care professionals are poorly prepared by their education for
      their roles on the team. In parallel, there are increasing demands from consumers
      for health care professionals to serve the interests of society and patients
      through engaging in effective professional partnerships. Professionalism for
      health care providers is now being defined as a commitment to standards of
      excellence in the practice of the profession that are designed primarily to serve
      the interests of the patient and to be responsive to the health needs of society.
      Yet, there are multiple barriers impeding the development of professionalism
      beyond a uni-professional frame of reference. METHOD: Incorporating teamwork and
      professionalism into health care professional curricula at pre-registration level
      is proving to be challenging. These 2 areas of learning are brought together in
      this paper through a discussion of the role of interprofessional education in
      preparing all health care professional students for the workforce. CONCLUSION:
      Interprofessionalism is presented as a pre-registration curriculum framework that
      includes values shared by all health care professionals, which should be learned
      in order to more adequately prepare students for working in health care teams. It
      will be argued that interprofessional education provides appropriate methods by
      which to learn interprofessionalism, and that this will ultimately contribute to
      overcoming uni-professional exclusivity.

PMID- 15842680
TI  - Misunderstandings: a qualitative study of primary care consultations in
      multilingual settings, and educational implications.
AB  - BACKGROUND: Patients in inner-city areas come from increasingly diverse language
      and cultural backgrounds. Neither communications training modelled on local
      English speakers nor the provision of interpreters offer adequate solutions. AIM:
      To identify how patients with limited English and culturally different
      communication styles consult with general practitioners (GPs) in English, and to
      develop training strategies from both good practice and observed
      misunderstandings. METHODS: Randomly selected routine and emergency surgeries in
      19 inner London general practices were video-recorded. The videos were viewed
      independently by 2 discourse analysts. Key consultations, across a wide range of
      English language ability, were selected and transcribed to analyse
      misunderstandings resulting from language/cultural differences. RESULTS: Of the
      232 video recordings that were made, 20% were with patients with limited English
      and contained major and often extended misunderstandings. QUALITATIVE ANALYSIS:
      Four main categories of patient 'talk' contributing to misunderstandings are
      identified: (1) pronunciation and word stress; (2) intonation and speech
      delivery; (3) grammar, vocabulary and lack of contextual information; and (4)
      style of presentation. The importance of different styles of self-presentation by
      patients as the reason for misunderstandings is highlighted. On only 3 occasions
      were culturally specific health beliefs raised. CONCLUSION: It is routine for GPs
      in inner London practices to manage consultations with patients with culturally
      different communicative styles from their own. Specific training in identifying
      these problems and preventing/repairing them in the consultation is essential.
      This level of awareness-raising is more crucial than general discussions of
      culturally different health belief models.

PMID- 15842681
TI  - Communication, stress and distress: evolution of an individual support programme
      for medical students and doctors.
AB  - BACKGROUND: The stress and distress that can be associated with poor
      communication is well recognised. The problem of how to manage this effectively
      has yet to be solved. METHODS: In December 2001, the Communication Skills Unit
      sited in the Department of General Practice in the University of Wales, College
      of Medicine set up a pilot project for medical students and qualified doctors who
      were perceived to have communication difficulties. Referrals were made via the
      deaneries following an agreed format. Initial assessments were used to build an
      individually tailored programme addressing clients' needs. DISCUSSION: Throughout
      the year a variety of problems were encountered ranging from language
      difficulties to bullying and mental health issues. Anecdotal evidence of
      improvements has been clear, but measuring the outcome of this intervention has
      proved to be more challenging. Our efforts are now focused on refining assessment
      and evaluation. This type of service can provide the link between national and
      local initiatives as well as helping to develop strategies for assessment and
      training in communication.

PMID- 15842682
TI  - A structured communication adolescent guide (SCAG): assessment of reliability and
      validity.
AB  - PURPOSE: To assess the reliability and validity of a Structured Communication
      Adolescent Guide (SCAG) in an undergraduate medical education setting using
      trained adolescent raters. METHOD: The SCAG is a 49-item, 6-section (A-F),
      protocol derived from the Calgary Cambridge Observation Guide that incorporates
      adolescent psychosocial data collection with the physician's communication
      skills. Four trained female adolescents scored 42 videotaped adolescent clinical
      encounters using the SCAG; a trained psychologist's rating for each videotape was
      used as the gold standard. RESULTS: Agreement among adolescent raters was
      determined by calculating intraclass correlation coefficients (ICC). The
      individual SCAG item scores, combined with the global ratings for each section,
      resulted in an overall ICC value of 0.93, indicating very strong agreement among
      the 4 raters. The global rating scores for the sections ('initiating the
      session', 'initiating separation', 'once adolescent is alone--lifestyle' and
      'closure') produced an ICC range of 0.58-0.93. However, the ICC values for the 2
      remaining sections ('how was information collected' and 'gathering information')
      global rating scores were below 0.30, signifying low agreement. Overall agreement
      between the adolescent raters and the gold standard resulted in an ICC value of
      0.78. This is evidence of the SCAG's criterion validity. CONCLUSION: The SCAG is
      a reasonably valid tool for use in guiding an encounter with an adolescent
      patient. However, 2 sections require modifications to improve their reliability
      and thus the SCAG's overall performance. Our results suggest that the SCAG shows
      promise as a potentially useful teaching resource in undergraduate medical
      education in adolescent medical interviewing.

PMID- 15842683
TI  - How should trainees be taught to open a clinical interview?
AB  - AIM: To characterise the opening of secondary care consultations. METHOD: We
      audio-taped 17 first consultations in medical clinics, transcribed them verbatim,
      and analysed verbal interactions from when the doctor called the patient into the
      consulting room to when she or he asked clarifying questions. RESULTS: The
      interviews did not open with the sequence, reported by previous researchers, of
      'doctor's soliciting question, patient's opening statement, interruption by the
      doctor'. Doctors (1) called the patient to the consultation; (2) greeted them;
      (3) introduced themselves; (4) made a transition to clinical talk; and (5) framed
      the consultation. They used a referral letter, the case notes, computer records
      and their prior knowledge of the patient to help frame the consultation, and did
      so informally and with humour. CONCLUSION: These 5 steps could help trainees
      create a context for active listening that is less prone to interruption.

PMID- 15842684
TI  - Exploring family physicians' reactions to multisource feedback: perceptions of
      credibility and usefulness.
AB  - PURPOSE: Physician performance is comprised of several domains of professional
      competence. Multisource feedback (MSF) or 360-degree feedback is an approach used
      to assess these, particularly the humanistic and relational competencies.
      Research studying responses to performance assessment shows that reactions vary
      and can influence how performance feedback is used. Improvement does not always
      result, especially when feedback is perceived as negative. This small qualitative
      study undertook preliminary exploration of physicians' reactions to MSF, and
      perceptions influencing these and the acceptance and use of their feedback.
      METHODS: We held focus groups with 15 family physicians participating in an MSF
      pilot study. Qualitative analyses included content and constant comparative
      analyses. RESULTS: Participants agreed that the purpose of MSF assessment should
      be to enhance practice and generally agreed with their patients' feedback.
      However, responses to medical colleague and co-worker feedback ranged from
      positive to negative. Several participants who responded negatively did not agree
      with their feedback nor were inclined to use it for practice improvement.
      Reactions were influenced by perceptions of accuracy, credibility and usefulness
      of feedback. Factors shaping these perceptions included: recruiting credible
      reviewers, ability of reviewers to make objective assessments, use of the
      assessment tool and specificity of the feedback. CONCLUSION: Physicians'
      perceptions of the MSF process and feedback can influence how and if they use the
      feedback for practice improvement. These findings are important, raising the
      concern that feedback perceived as negative and not useful will have no or
      negative results, and highlight questions for further study.

PMID- 15842687
TI  - Process of integration of 12 cross-cutting themes.

PMID- 15842688
TI  - Using Fetal Alcohol Syndrome as an integrating curricular theme.

PMID- 15842689
TI  - Radical curriculum design: an experiment in learner empowerment.

PMID- 15842690
TI  - A business of medicine curriculum for medical students.

PMID- 15842691
TI  - Geriatrics curriculum for clerkship students: implementation and evaluation.

PMID- 15842692
TI  - Widening participation in medicine.

PMID- 15842693
TI  - Patient safety in an interprofessional learning environment.

PMID- 15842694
TI  - Enhancing EBM skills using goal setting and peer teaching.

PMID- 15842695
TI  - Medical student education: addressing patients' mental health needs.

PMID- 15842696
TI  - Ensuring medical student competency in basic procedural skills.

PMID- 15842697
TI  - A successful format for a breastfeeding advocacy skills workshop.

PMID- 15842698
TI  - Teaching students to use medical notes.

PMID- 15842699
TI  - A student-organised introduction to clinical rotations.

PMID- 15842700
TI  - An innovative advanced patient-doctor course for medical students.

PMID- 15842701
TI  - Does direct observation improve medical students' clerkship experiences?

PMID- 15842702
TI  - Deaf awareness and sign language: an innovative special study module.

PMID- 15842703
TI  - All the world's a stage...

PMID- 15842704
TI  - Does 'doing art' inform students' learning of anatomy?

PMID- 15842705
TI  - Interactive drama: teaching aboriginal health medical education.

PMID- 15842706
TI  - Simulation of paediatric basic life support on the Internet.

PMID- 15842707
TI  - Using web-based technology to teach physical examination.

PMID- 15842708
TI  - Team learning in a medical gross anatomy course.

PMID- 15842709
TI  - Reflective teaching: the value of e-mail student journaling.

PMID- 15842710
TI  - Interactive online assessment training for busy practitioners.

PMID- 15842711
TI  - Problem-based learning using a human patient simulator.

PMID- 15842712
TI  - Praxis Pointers: reciprocal publication of practical pearls.

PMID- 15842713
TI  - Online simulations of ambulatory care for medical residents.

PMID- 15842714
TI  - The impact of duty hour restrictions on teaching by surgical residents.

PMID- 15842715
TI  - The OSCE as a formative evaluation tool for substance abuse teaching.

PMID- 15842716
TI  - Bioethics curriculum for paediatrics residents: implementation and evaluation.

PMID- 15842717
TI  - Are there specific competencies required by prison GPs?

PMID- 15842718
TI  - Cabin Fever: an innovation in faculty development for rural preceptors.

PMID- 15842719
TI  - A scholarship-generating project for clinician educators.

PMID- 15842720
TI  - Wessex Professional Programme: general professional development for SpRs.

PMID- 15842721
TI  - Stories as data, data as stories: making sense of narrative inquiry in clinical
      education.
AB  - BACKGROUND: Narrative inquiry is a form of qualitative research that takes story
      as either its raw data or its product. Science and narrative can be seen as two
      kinds of knowing, reflected in the distinction between evidence-based medicine
      derived from population studies and narrative-based medicine focused upon the
      single case. A similar tension exists in the field of narrative inquiry between
      cognitive-orientated analytical methods and affective-orientated methods of
      synthesis. AIMS: This paper aims to make sense of narrative inquiry in clinical
      education through definition of 'narrative', articulation of a typology of
      narrative research approaches, and critical examination in particular of
      analytical methods, the dominant approach in the literature. The typology is
      illustrated by research examples, and the role of medical education in developing
      expertise in narrative inquiry is discussed. An argument is made that the tension
      between analysis of the structure of stories and empathic use of stories can be
      seen as productive, stimulating expertise encompassing both approaches.
      DISCUSSION: Analytical methods tend to lose the concrete story and its emotional
      impact to abstract categorizations, which may claim explanatory value but often
      remain descriptive. Stemming from discomfort with more integrative methods
      derived from the humanities, a science-orientated medical education may privilege
      analytical methods over approaches of synthesis. Medical education can redress
      this imbalance through attention to 'thinking with stories' to gain empathy for a
      patient's experience of illness. Such an approach can complement understanding of
      story as discourse - how narratives may be used rhetorically to manage both
      social interactions and identity.

PMID- 15842722
TI  - Access to essential medicines: a Hobbesian social contract approach.
AB  - Medicines that are vital for the saving and preserving of life in conditions of
      public health emergency or endemic serious disease are known as essential
      medicines. In many developing world settings such medicines may be unavailable,
      or unaffordably expensive for the majority of those in need of them. Furthermore,
      for many serious diseases (such as HIV/AIDS and tuberculosis) these essential
      medicines are protected by patents that permit the patent-holder to operate a
      monopoly on their manufacture and supply, and to price these medicines well above
      marginal cost. Recent international legal doctrine has placed great stress on the
      need to globalise intellectual property rights protections, and on the rights of
      intellectual property rights holders to have their property rights enforced.
      Although international intellectual property rights law does permit compulsory
      licensing of protected inventions in the interests of public health, the use of
      this right by sovereign states has proved highly controversial. In this paper I
      give an argument in support of states' sovereign right to expropriate private
      intellectual property in conditions of public health emergency. This argument
      turns on a social contract argument for the legitimacy of states. The argument
      shows, further, that under some circumstances states are not merely permitted
      compulsory to license inventions, but are actually obliged to do so, on pain of
      failure of their legitimacy as sovereign states. The argument draws freely on a
      loose interpretation of Thomas Hobbes's arguments in his Leviathan, and on an
      analogy between his state of War and the situation of public health disasters.

PMID- 15842723
TI  - Defining standard of care in the developing world: the intersection of
      international research ethics and health systems analysis.
AB  - In recent years there has been intense debate regarding the level of medical care
      provided to 'standard care' control groups in clinical trials in developing
      countries, particularly when the research sponsors come from wealthier countries.
      The debate revolves around the issue of how to define a standard of medical care
      in a country in which many people are not receiving the best methods of medical
      care available in other settings. In this paper, we argue that additional
      dimensions of the standard of care have been hitherto neglected, namely, the
      structure and efficiency of the national health system. The health system affects
      locally available medical care in two important ways: first, the system may be
      structured to provide different levels of care at different sites with referral
      mechanisms to direct patients to the appropriate level of care. Second,
      inefficiencies in this system may influence what care is available in a
      particular locale. As a result of these two factors locally available care cannot
      be equated with a national 'standard'. A reasonable approach is to define the
      national standard of care as the level of care that ought to be delivered under
      conditions of appropriate and efficient referral in a national system. This
      standard is the minimum level of care that ought to be provided to a control
      group. There may be additional moral arguments for higher levels of care in some
      circumstances. This health system analysis may be helpful to researchers and
      ethics committees in designing and reviewing research involving standard care
      control groups in developing country research.

PMID- 15842724
TI  - An unequal activism for an unequal epidemic?
AB  - This paper observes that a substantially large moral duty of dealing with the
      AIDS situation in Africa has been placed on the drug companies and argues that
      this approach is inequitable. Using the poverty-AIDS relationship and the human
      rights framework it argues for a more balanced AIDS activism, which puts equal
      pressure on all potential stakeholders in the war against AIDS. It argues that
      this redistribution of the HIV/AIDS moral burden is perhaps the only hope for
      curbing the African AIDS epidemic that continues to ravage communities on that
      continent.

PMID- 15842725
TI  - Many worlds, one ethic: design and development of a global research ethics
      training curriculum.
AB  - The demand for basic research ethics training has grown considerably in the past
      few years. Research and education organizations face the challenge of providing
      this training with limited resources and training tools available. To meet this
      need, Family Health International (FHI), a U.S.-based international research
      organization, recently developed a Research Ethics Training Curriculum (RETC). It
      was designed as a practical, user-friendly tool that provides basic, up-to-date,
      standardized training on the ethics of human research. The curriculum can easily
      be adapted to different audiences and training requirements. The RETC was
      reviewed by a group of international experts and field tested in five countries.
      It is available in English, French, and Spanish as a three-ring binder and CD
      ROM, as well as on the Web. It may be used as either an interactive self-study
      program or for group training.

PMID- 15842726
TI  - Developing medical ethics in China's reform era.
AB  - The paper gives an analytical synopsis of the problem of developing medical
      ethics in the early half of the 1990s in China, as perceived by Chinese scholars
      and medical professionals interested in medical ethics. The views captured and
      analyzed here were expressed in one of the two major journals on medical ethics
      in China: Chinese Medical Ethics. The economic reform unleashed profound changes
      in Chinese society, including in the medical field, creating irregularities and
      improprieties in the profession. Furthermore, the market reform also created new
      values that were in tension with existing values. In this transitional period,
      Chinese medical ethicists saw the need to rebuild medical morality for the new
      era. Using the code of conduct promulgated by the Chinese Ministry of Health in
      1989 as a basis, assessment and education aspects of the institutionalization of
      medical ethics are discussed. In addition to institutional problems of
      institutionalising ethics, there are philosophical and methodological issues that
      are not easy to solve. After all, to institutionalize medical ethics is no easy
      task for a country as old and as big as China. Chinese medical ethicists seem
      ready to confront these difficulties in their effort to develop medical ethics in
      Reform China.

PMID- 15842728
TI  - Society of General Internal Medicine, 28th annual meeting, New Orleans,
      Louisiana, USA, May 11-14, 2005.

PMID- 15842729
TI  - Type 1 diabetes in the Spanish population: additional factors to class II HLA-DR3
      and -DR4.
AB  - BACKGROUND: The Major Histocompatibility Complex is the main genetic contributor
      to susceptibility to type 1 diabetes (T1D); genome-wide scans have consistently
      mapped increased predisposition to this region. The highest disease risk has been
      associated with HLA-DR3 and HLA-DR4. In particular, the DR3-positive ancestral
      haplotype 18.2 was reported as highly diabetogenic. We aimed to corroborate
      whether this haplotype increases the susceptibility conferred by the DQ2-DR3
      alleles in a Mediterranean population. We also searched for additional
      susceptibility factors to the classic DQ2-DR3 and DQ8-DR4. RESULTS: Genetic MHC
      markers were analysed in a case-control study with 302 T1D patients and 529
      ethnically matched controls. DR3-TNFa1b5 carrier rate was significantly higher in
      DR3-positive heterozygous T1D patients than in DR3-positive heterozygous controls
      (p = 0.0019; odds ratio OR [95% confidence interval CI] = 2.26 [1.3-3.93]). This
      data was confirmed analysing the allelic frequency, which includes the
      information corresponding to the DR3-homozygous individuals (p = 0.001; OR =
      2.09) and by using the Arlequin software to check the DR3-positive haplotypes (p
      = 0.004;OR = 1.93). The present results provide strong evidence of a second
      susceptibility region in the ancestral haplotype 18.2 in the Spanish population.
      Moreover, we searched for T1D susceptibility factors in addition to the MHC
      classical ones, within the DR2-DQ6/DR3-DQ2/DR4-DQ8 negative population. Several
      genetic markers in both MHC class II (DQA1*0101-DQB1*0501 [p = 0.007;OR = 2.81],
      DQA1*0201-DQB1*0202 [p = 0.03; OR = 2.35]) and III (TNFa2b1 [p = 0.01 OR = 2.74],
      BAT-2*2 [p = 0.004; OR = 3.19]) were found. These different alleles associated
      with T1D were not independent and we observed linkage disequilibrium among them
      leading us to describe two new risk haplotypes (DQA1*0101-DQB1*0501-TNFa2b1 and
      DQA1*0201-DQB1*0202- BAT-2*2). Finally, we studied a T1D
      susceptibility/protection marker located in extended class I, D6S2223; however,
      no association was observed in our population. CONCLUSION: Our results suggest
      that other associated MHC haplotypes might present susceptibility factors in loci
      different from HLA-class II and that the class II molecules are not necessarily
      the universal etiologic factor in every MHC haplotype.

PMID- 15842730
TI  - Kinetics and isotype profile of antibody responses in rhesus macaques induced
      following vaccination with HPV 6, 11, 16 and 18 L1-virus-like particles
      formulated with or without Merck aluminum adjuvant.
AB  - BACKGROUND: Human papillomaviruses (HPV) are the most common sexually transmitted
      viruses. Infection of the cervical epithelium by HPVs can lead to the development
      of cervical cancer. Recent advances in vaccine research have shown that
      immunization with papillomavirus-like particles (VLPs) containing the major
      structural viral protein, L1 from HPV 16 can provide protection from the
      establishment of a chronic HPV 16 infection and related cervical intraepithelial
      neoplasia (CIN) in baseline HPV 16 naive women. METHODS: To better understand the
      quantitative and qualitative effects of aluminum adjuvant on the immunogenic
      properties of an HPV 6, 11, 16 and 18L1 VLP vaccine, we used an HPV-specific,
      antibody isotyping assay and a competitive immunoassay that measures antibodies
      to neutralizing epitopes to profile sera from rhesus macaques immunized with the
      HPV L1 VLP vaccine formulated with or without aluminum adjuvant. RESULTS:
      Immunization with VLPs formulated with the aluminum adjuvant elicited a
      significantly stronger immune response with higher peak antibody titers both at
      four weeks post vaccination (12.7 to 41.9-fold higher) as well as in the
      persistent phase at week 52 (4.3 to 26.7-fold higher) than that of VLPs alone.
      Furthermore, the aluminum adjuvant formulated HPV VLP vaccine elicited a
      predominantly T helper type 2 response, with high levels of IgG1 and IgG4 and low
      levels of IgG2. The vaccine also elicited high levels of serum IgA, which may be
      important in providing mucosal immunity to impart protection in the anogenital
      tract. CONCLUSION: These results show that the HPV 6, 11, 16 and 18 L1-VLP
      vaccine formulated with Merck aluminum adjuvant elicits a robust and durable
      immune response and holds promise as a vaccine for preventing cervical cancer.

PMID- 15842731
TI  - EBV latent membrane protein 1 abundance correlates with patient age but not with
      metastatic behavior in north African nasopharyngeal carcinomas.
AB  - BACKGROUND: Undifferentiated nasopharyngeal carcinomas are rare in a majority of
      countries but they occur at a high incidence in South China and to a lesser
      extent in North Africa. They are constantly associated with the Epstein-Barr
      virus (EBV) regardless of patient geographic origin. In North Africa, the
      distribution of NPC cases according to patient age is bi-modal with a large group
      of patients being around 50 years old (80%) and a smaller group below 25 years
      old. We and others have previously shown that the juvenile form of NPC has
      distinct biological characteristics including a low amount of p53 and Bcl2 in the
      tumor tissue and a low level of anti-EBV IgG and IgA in the peripheral blood.
      RESULTS: To get more insight on potential oncogenic mechanisms specific of these
      two forms, LMP1 abundance was assessed in 82 NPC patients of both groups, using
      immuno-histochemistry and semi-quantitative evaluation of tissue staining. Serum
      levels of anti-EBV antibodies were simultaneously assessed. For LMP1 staining, we
      used the S12 antibody which has proven to be more sensitive than the common anti
      LMP1 CS1-4 for analysis of tissue sections. In all NPC biopsies, at least a small
      fraction of cells was positively stained by S12. LMP1 abundance was strongly
      correlated to patient age, with higher amounts of the viral protein detected in
      specimens of the juvenile form. In contrast, LMP1 abundance was not correlated to
      the presence of lymph node or visceral metastases, nor to the risk of metastatic
      recurrence. It was also independent of the level of circulating anti-EBV
      antibodies. CONCLUSION: The high amount of LMP1 recorded in tumors from young
      patients confirms that the juvenile form of NPC has specific features regarding
      not only cellular but also viral gene expression.

PMID- 15842732
TI  - Evaluation of the VP22 protein for enhancement of a DNA vaccine against anthrax.
AB  - BACKGROUND: Previously, antigens expressed from DNA vaccines have been fused to
      the VP22 protein from Herpes Simplex Virus type I in order to improve efficacy.
      However, the immune enhancing mechanism of VP22 is poorly understood and initial
      suggestions that VP22 can mediate intercellular spread have been questioned.
      Despite this, fusion of VP22 to antigens expressed from DNA vaccines has improved
      immune responses, particularly to non-secreted antigens. METHODS: In this study,
      we fused the gene for the VP22 protein to the gene for Protective Antigen (PA)
      from Bacillus anthracis, the causative agent of anthrax. Protective immunity
      against infection with B. anthracis is almost entirely based on a response to PA
      and we have generated two constructs, where VP22 is fused to either the N- or the
      C-terminus of the 63 kDa protease-cleaved fragment of PA (PA63). RESULTS:
      Following gene gun immunisation of A/J mice with these constructs, we observed no
      improvement in the anti-PA antibody response generated. Following an
      intraperitoneal challenge with 70 50% lethal doses of B. anthracis strain STI
      spores, no difference in protection was evident in groups immunised with the DNA
      vaccine expressing PA63 and the DNA vaccines expressing fusion proteins of PA63
      with VP22. CONCLUSION: VP22 fusion does not improve the protection of A/J mice
      against live spore challenge following immunisation of DNA vaccines expressing
      PA63.

PMID- 15842733
TI  - SYK expression in human breast cancer.
AB  - BACKGROUND: Syk (Splenic Tyrosine Kinase) is an intracellular receptor protein
      kinase involved in cell proliferation, differentiation and phagocytosis. It has
      been studied in T and B lymphocytes, NK cells and platelets. The strong
      expression of Syk in mammary gland prompted research into its potential role in
      mammary carcinogenesis. There have been very few studies about its role in breast
      cancer with conflicting results. This study aims to investigate the hypothesis
      that Syk expression is down-regulated in breast cancer compared with ANCT and the
      association between its expression and clinicopathological parameters. MATERIALS
      AND METHODS: mRNA was extracted from 48 breast cancer specimens. Relative Syk to
      ribosomal RNA expression was determined by RT-PCR and Taqman methodology. Mann
      Whitney U test was used to examine the association between Syk expression in
      cancer and ANCT. Spearman's rank correlation test was used to examine the
      association between Syk expression in tumours and patients' age, tumour size,
      tumour grade, estrogen and progesterone receptor status, lymph node metastasis,
      vascular invasion and clinical outcome. RESULTS: The median for the relative
      value of Syk expression was 0.17 and 0.18 (range: 0.12 - 0.56 and 0.0 - 1.77) for
      tumours and ANCT respectively. There was no significant association between Syk
      expression in cancers and ANCT (p= 0.598) nor between Syk expression in tumours
      and patients' age, tumour size, tumour grade, estrogen and progesterone receptor
      status, lymph node metastasis, vascular invasion or prognosis. CONCLUSION: This
      study shows that Syk mRNA expression does not seem to vary between breast tumours
      and ANCT. Furthermore, we observed no significant association between Syk
      expression and clinicopathological parameters.

PMID- 15842735
TI  - Detection of large deletions in the LDL receptor gene with quantitative PCR
      methods.
AB  - BACKGROUND: Familial Hypercholesterolemia (FH) is a common genetic disease and at
      the molecular level most often due to mutations in the LDL receptor gene. In
      genetically heterogeneous populations, major structural rearrangements account
      for about 5% of patients with LDL receptor gene mutations. METHODS: In this study
      we tested the ability of two different quantitative PCR methods, i.e. Real-Time
      PCR and Multiplex Ligation-Dependent Probe Amplification (MLPA), to detect
      deletions in the LDL receptor gene. We also reassessed the contribution of major
      structural rearrangements to the mutational spectrum of the LDL receptor gene in
      Denmark. RESULTS: With both methods it was possible to discriminate between one
      and two copies of the LDL receptor gene exon 5, but the MLPA method was cheaper,
      and it was far more accurate and precise than Real-Time PCR. In five of 318
      patients with an FH phenotype, MLPA analysis revealed five different deletions in
      the LDL receptor gene. CONCLUSION: The MLPA method was accurate, precise and at
      the same time effective in screening a large number of FH patients for large
      deletions in the LDL receptor gene.

PMID- 15842736
TI  - Quantitative immuno-electron microscopic analysis of nuclear respiratory factor 2
      alpha and beta subunits: Normal distribution and activity-dependent regulation in
      mammalian visual cortex.
AB  - The macaque visual cortex is exquisitely organized into columns, modules, and
      streams, much of which can be correlated with its metabolic organization revealed
      by cytochrome oxidase (CO). Plasticity in the adult primate visual system has
      also been documented by changes in CO activity. Yet, the molecular mechanism of
      regulating this enzyme remains not well understood. Being one of only four
      bigenomic enzymes in mammalian cells, the transcriptional regulation of this
      enzyme necessitates a potential bigenomic coordinator. Nuclear respiratory factor
      2 (NRF-2) or GA-binding protein is a transcription factor that may serve such a
      critical role. The goal of the present study was to determine if the two major
      subunits of NRF-2, 2alpha and 2beta, had distinct subcellular distribution in
      neurons of the rat and monkey visual cortex, if major metabolic neuronal types in
      the macaque exhibited different levels of the two subunits, and if they would
      respond differently to monocular impulse blockade. Quantitative immuno-electron
      microscopy was used. In both rats and monkeys, nuclear labeling of alpha and beta
      subunits was mainly over euchromatin rather than heterochromatin, consistent with
      their active participation in transcriptional activity. Cytoplasmic labeling was
      over free ribosomes, the Golgi apparatus, and occasionally the nuclear envelope,
      signifying sites of synthesis and possible posttranslational modifications. The
      density of both subunits was much higher in the nucleus than in the cytoplasm for
      all neurons examined, again indicating that their major sites of cellular action
      is in the nucleus.

PMID- 15842737
TI  - Subcellular localization of phosducin in rod photoreceptors.
AB  - Phosducin (Pd) is a 28-kD phosphoprotein whose expression in retina appears
      limited to photoreceptor cells. Pd binds to the beta,gamma subunits of transducin
      (Gt). Their binding affinity is markedly diminished by Pd phosphorylation. While
      Pd has long been regarded as a candidate for the regulation of Gt, the molecular
      details of Pd function remain unclear. This gap in understanding is due in part
      to a lack of precise information concerning the total amount and subcellular
      localization of rod Pd. While earlier studies suggested that Pd was a rod outer
      segment (ROS) protein, recent findings have demonstrated that Pd is distributed
      throughout the rod. In this report, the subcellular distribution and amounts of
      rat Pd are quantified with immunogold electron microscopy. After light or dark
      adaptation, retinal tissues were fixed in situ and prepared for ultrathin
      sectioning and immunogold labeling. Pd concentrations were analyzed over the
      entire length of the rod. The highest Pd labeling densities were found in the rod
      synapse. Less intense Pd staining was observed in the ellipsoid and myoid
      regions, while minimal labeling densities were found in the ROS and the rod
      nucleus. In contrast with rod Gt, no evidence was found for light-dependent
      movement of Pd between inner and outer segments. There is a relative paucity of
      Pd in the ROS as compared with the large amounts of Gt found there. This does not
      support the earlier idea that Pd could modulate Gt activity by controlling its
      concentration. On the other hand, the presence of Pd in the nucleus is consistent
      with its possible role as a regulator of transcription. The functions of Pd in
      the ellipsoid and myoid regions remain unclear. The highest concentration of Pd
      was found at the rod synapse, consistent with a suggested role for Pd in the
      regulation of synaptic function.

PMID- 15842738
TI  - Normal eye-specific patterning of retinal inputs to murine subcortical visual
      nuclei in the absence of brain-derived neurotrophic factor.
AB  - Brain-derived neurotrophic factor (BDNF) is a preferred ligand for a member of
      the tropomyosin-related receptor family, trkB. Activation of trkB is implicated
      in various activity-independent as well as activity-dependent growth processes in
      many developing and mature neural systems. In the subcortical visual system,
      where electrical activity has been implicated in normal development, both
      differential survival, as well as remodeling of axonal arbors, have been
      suggested to contribute to eye-specific segregation of retinal ganglion cell
      inputs. Here, we tested whether BDNF is required for eye-specific segregation of
      visual inputs to the lateral geniculate nucleus and the superior colliculus, and
      two other major subcortical target fields in mice. We report that eye-specific
      patterning is normal in two mutants that lack BDNF expression during the
      segregation period: a germ-line knockout for BDNF, and a conditional mutant in
      which BDNF expression is absent or greatly reduced in the central nervous system.
      We conclude that the availability of BDNF is not necessary for eye-specific
      segregation in subcortical visual nuclei.

PMID- 15842739
TI  - Unilateral photoreceptor rescue can improve the ability of the opposite,
      untreated, eye to drive cortical cells in a retinal degeneration model.
AB  - In the Royal College of Surgeons, rat photoreceptor degeneration occurs over the
      first several months of life, causing deterioration of visual cortical
      responsiveness seen as greater numbers of cells being nonresponsive to visual
      stimulation, poor tuning of those cells that do respond, and an overall tendency
      for domination by the contralateral visual input. If the progress of degeneration
      in one eye is slowed by intraretinal cell transplantation, cortical responses to
      stimulation of the remaining, untreated, eye are much stronger, better tuned and
      histograms of ocular dominance resemble more those in normal rats. This suggests
      that the rescued eye is able to enhance performance in the untreated eye by some
      form of postsynaptic mechanism.

PMID- 15842740
TI  - Effect of temporal sparseness and dichoptic presentation on multifocal visual
      evoked potentials.
AB  - Multifocal VEP (mfVEP) responses were obtained from 13 normal human subjects for
      nine test conditions, covering three viewing conditions (dichoptic and left and
      right monocular), and three different temporal stimulation forms (rapid contrast
      reversal, rapid pattern pulse presentation, and slow pattern pulse presentation).
      The rapid contrast reversal stimulus had pseudorandomized reversals of
      checkerboards in each visual field region at a mean rate of 25 reversals/s,
      similar to most mfVEP studies to date. The rapid pattern pulse presentation had
      pseudorandomized presentations of a checkerboard for one frame, interspersed with
      uniform grey frames, with a mean rate of 25 presentations/s per region per eye.
      The slow pattern pulse stimulus had six presentations/s per region per eye.
      Recording time was 5.3 min/condition. For dichoptic presentation slow pattern
      pulse responses were 4.6 times larger in amplitude than the contrast reversal
      responses. Binocular suppression was greatest for the contrast reversal stimulus.
      Consideration of the signal-to-noise ratios indicated that to achieve a given
      level of reliability, slow pattern pulse stimuli would require half the recording
      time of contrast reversal stimuli for monocular viewing, and 0.4 times the
      recording time for dichoptically presented stimuli. About half the responses to
      the slow pattern pulse stimuli had peak value exceeding five times their
      estimated standard error. Responses were about 20% smaller in the upper visual
      field locations. Space-time decomposition showed that responses to slow pattern
      pulse were more consistent across visual field locations. We conclude that the
      pattern pulse stimuli, which we term temporally sparse, maintain the visual
      system in a high contrast gain state. This more than compensates for the smaller
      number of presentations in the run, and provides signal-to-noise advantages that
      may be valuable in clinical application.

PMID- 15842741
TI  - Reciprocal inhibition of voltage-gated potassium currents (I K(V)) by activation
      of cannabinoid CB1 and dopamine D1 receptors in ON bipolar cells of goldfish
      retina.
AB  - Cannabinoid CB1 receptor (via Gs) and dopamine D2 receptor (via Gi/o)
      antagonistically modulate goldfish cone membrane currents. As ON bipolar cells
      have CB1 and D1 receptors, but not D2 receptors, we focused on whether CB1
      receptor agonist and dopamine interact to modulate voltage-dependent outward
      membrane K+ currents I K(V) of the ON mixed rod/cone (Mb) bipolar cells. Whole
      cell currents were recorded from Mb bipolar cells in goldfish retinal slices. Mb
      bipolar cells were identified by intracellular filling with Lucifer yellow. The
      bath solution was calcium-free and contained 1 mM cobalt to block indirect
      calcium-dependent effects. Dopamine (10 microM) consistently increased I K(V) by
      a factor of 1.57 +/- 0.12 (S.E.M., n = 15). A CB receptor agonist, WIN 55212-2
      (0.25-1 microM), had no effect, but 4 microM WIN 55212-2 suppressed I K(V) by
      60%. If I K(V) was first increased by 10 microM dopamine, application of WIN
      55212-2 (0.25-1 microM) reversibly blocked the effect of dopamine even though
      these concentrations of WIN 55212-2 had no effect of their own. If WIN 55212-2
      was applied first and dopamine (10 microM) was added to the WIN-containing
      solution, 0.1 microM WIN 55212-2 blocked the effect of dopamine. All effects of
      WIN 55212-2 were blocked by coapplication of SR 141716A (CB1 antagonist) and
      pretreatment with pertussis toxin (blocker of Gi/o) indicating action via CB1
      receptor activation of G protein Gi/o. Coactivation of CB1 and D1 receptors on Mb
      bipolar cells produces reciprocal effects on I K(V). The CB1-evoked suppression
      of I K(V) is mediated by G protein Gi/o, whereas the D1-evoked enhancement is
      mediated by G protein Gs. As dopamine is a retinal "light" signal, these data
      support our notion that endocannabinoids function as a "dark" signal, interacting
      with dopamine to set retinal sensitivity.

PMID- 15842742
TI  - Simulation analysis of receptive-field size of retinal horizontal cells by ionic
      current model.
AB  - The size of the receptive field of retinal horizontal cells changes with the
      state of dark/light adaptation. We have used a mathematical model to determine
      how changes in the membrane conductance affect the receptive-field properties of
      horizontal cells. We first modeled the nonlinear membrane properties of
      horizontal cells based on ionic current mechanisms. The dissociated horizontal
      cell model reproduced the voltage-current (V-I) relationships for various
      extracellular glutamate concentrations measured in electrophysiological studies.
      Second, a network horizontal cell model was also described, and it reproduced the
      V-I relationship observed in vivo. The network model showed a bell-shaped
      relationship between the receptive-field size and constant glutamate
      concentration. The simulated results suggest that the calcium current is a
      candidate for the bell-shaped length constant relationship.

PMID- 15842743
TI  - Changes in human short-wavelength-sensitive and achromatic resolution acuity with
      retinal eccentricity and meridian.
AB  - Psychophysical measurements using achromatic grating resolution acuity in
      peripheral vision show a prominent retinal asymmetry in acuity which is
      consistent with predicted values based on available estimates of midget ganglion
      cell density. Recent studies have shown that peripheral grating resolution acuity
      values for short-wavelength-sensitive (SWS) isolating gratings in normal
      observers are closely related to predicted values based on the underlying small
      bistratified ganglion cell density. By measuring SWS resolution acuity at
      different locations across the visual field, we wished to see if any significant
      acuity asymmetry exists for the short-wavelength system. In addition to this, we
      wanted to compare SWS and achromatic resolution acuity at different retinal
      locations of equal eccentricity. SWS and achromatic grating resolution acuity was
      measured in two observers at a number of different retinal meridians of 10- and
      25-deg eccentricity from the fovea, and out to 35-deg eccentricity along the
      horizontal meridian. Achromatic resolution acuity was higher than SWS resolution
      acuity at all locations. At 10-deg eccentricity there was slight radial asymmetry
      in SWS and achromatic acuity, both displaying highest acuity along the horizontal
      meridian. At 25-deg eccentricity, SWS and achromatic acuity showed significant
      asymmetry with acuity being higher in the nasal retina compared to the temporal
      retina and with higher acuity in the superior retina compared to the inferior
      retina. At 35-deg eccentricity, the acuity asymmetry along the horizontal
      meridian was maintained with acuity for both significantly higher in the nasal
      retina. The SWS acuity changes with eccentricity and meridian were qualitatively
      similar to that found for achromatic acuity at the majority of retinal locations.
      Like achromatic acuity, SWS acuity shows significant asymmetry at different
      retinal locations of equal eccentricity. This suggests that both the midget and
      small bistratified ganglion cell population density changes significantly with
      retinal location and eccentricity. SWS acuity appears to change in parallel with
      achromatic acuity for the majority of retinal locations measured, although the
      amount of nasotemporal asymmetry appears to be slightly less for the SWS system
      at 25- and 35-deg eccentricity.

PMID- 15842744
TI  - The direction-selective contrast response of area 18 neurons is different for
      first- and second-order motion.
AB  - Cortical neurons selective for the direction of motion often exhibit some limited
      response to motion in their nonpreferred directions. Here we examine the
      dependence of neuronal direction selectivity on stimulus contrast, both for first
      order (luminance-modulated, sine-wave grating) and second-order (contrast
      modulated envelope) stimuli. We measured responses from single neurons in area 18
      of cat visual cortex to both kinds of moving stimuli over a wide range of
      contrasts (1.25-80%). Direction-selective contrast response functions (CRFs) were
      calculated as the preferred-minus-null difference in average firing frequency as
      a function of contrast. We also applied receiver operating characteristic
      analysis to our CRF data to obtain neurometric functions characterizing the
      potential ability of each neuron to discriminate motion direction at each
      contrast level tested. CRFs for sine-wave gratings were usually monotonic;
      however, a substantial minority of neurons (35%) exhibited nonmonotonic CRFs
      (such that the degree of direction selectivity decreased with increasing
      contrast). The underlying preferred and nonpreferred direction CRFs were diverse,
      often having different shapes in a given neuron. Neurometric functions for
      direction discrimination showed a similar degree of heterogeneity, including
      instances of nonmonotonicity. For contrast-modulated stimuli, however, CRFs for
      either carrier or envelope contrast were always monotonic. In a given neuron,
      neurometric thresholds were typically much higher for second- than for first
      order stimuli. These results demonstrate that the degree of a cell's direction
      selectivity depends on the contrast at which it is measured, and therefore is not
      a characteristic parameter of a neuron. In general, contrast response functions
      for first-order stimuli were very heterogeneous in shape and sensitivity, while
      those for second-order stimuli showed less sensitivity and were quite stereotyped
      in shape.

PMID- 15842745
TI  - Superimposed maps of the monocular visual fields in the caudolateral optic tectum
      in the frog, Rana pipiens.
AB  - The superficial layers of the frog optic tectum receive a projection from the
      contralateral eye that forms a point-to-point map of the visual field. The
      monocular part of the visual field of the contralateral eye is represented in the
      caudolateral region of the tectum while the binocular part of the visual field is
      represented in the rostromedial tectum. Within the representation of the
      binocular field (rostromedial tectum), the maps of visual space from each eye are
      aligned. The tectal representation of the binocular visual field of the
      ipsilateral eye is mediated through a crossed projection from the midbrain
      nucleus isthmi. This isthmotectal projection also terminates in the caudolateral
      region of the optic tectum, yet there has been no indication that it forms a
      functional connection. By extracellular recording in intermediate layer 7 of the
      caudolateral tectum, we have discovered electrical activity driven by visual
      stimulation in the monocular visual field of the ipsilateral eye. The units
      driven from the ipsilateral eye burst upon initial presentation of the stimulus.
      At individual layer 7 recording sites in the caudolateral tectum, the multiunit
      receptive field evoked from the ipsilateral eye is located at the mirror image
      spatial location to the multiunit receptive field driven by the contralateral
      eye. Thus, as revealed electrophysiologically, there are superimposed topographic
      maps of the monocular visual fields in the caudolateral tectum. The ipsilateral
      eye monocular visual field representation can be abolished by electrolytic
      ablation of contralateral nucleus isthmi.

PMID- 15842746
TI  - Melanopsin (Opn4) positive cells in the cat retina are randomly distributed
      across the ganglion cell layer.
AB  - A rare type of rodent retinal ganglion cell expresses melanopsin (Opn4), the
      majority of which project to the suprachiasmatic nuclei. Many of these cells are
      directly light sensitive and appear to regulate the circadian system in the
      absence of rod and cone photoreceptors. However, the rodent retina contains no
      overt regions of specialization, and the different ganglion cell types are hard
      to distinguish. Consequently, attempts to distinguish the distribution of
      melanopsin ganglion cells in relation to regions of retinal specialization or
      subtype have proved problematic. Retinal cells with a common function tend to be
      regularly distributed. In this study, we isolate cat melanopsin and label
      melanopsin expressing cells using in situ hybridization. The labelled cells were
      all confined to the ganglion cell layer, their density was low, and their
      distribution was random. Melanopsin containing cells showed no clear center-to
      periphery gradient in their distribution and were comprised of a relatively
      uniform cellular population.

PMID- 15842748
TI  - Feasibility study of online supercritical fluid extraction-liquid chromatography
      UV absorbance-mass spectrometry for the determination of proanthocyanidins in
      grape seeds.
AB  - Online coupling of supercritical fluid extraction (SFE) with liquid
      chromatography (LC)-UV absorbance-electrospray ionization (ESI)-mass spectrometry
      (MS) is evaluated for the determination of proanthocyanidins in grape seeds. The
      solid-phase intermediate trap is optimized in order to enhance the collection
      efficiency for the extracted polar components. Pure supercritical CO2 is used
      first to remove the oil in the seeds. Then methanol-modified CO2 is used to
      remove the polar components (e.g., phenolic compounds). Catechin and epicatechin
      (90%) are extracted out of the de-oiled after 240 min with 40% methanol as a
      modifier. Both singly-linked (B-type) and doubly-linked (A-type) procyanidins are
      identified by LC-ESI-MS, as well as their galloylated derivatives. The hyphenated
      system combines the extraction, separation, and detection in series. The
      experimental design minimizes the chance of analyte oxidation, degradation, and
      contamination. The traditional off-line SFE-LC method is also studied for
      comparison with the online method. Both advantages and disadvantages are observed
      for the online mode.

PMID- 15842749
TI  - Preparation and characterization of modified 3-aminopropylsilyl silica phases
      with 1,8-naphthalic anhydrides in HPLC.
AB  - Modified 3-aminopropylsilyl silica stationary phases with 1,8-naphthalic
      anhydrides [3-(1,8-naphthalimido)propyl (NAIP), 3-(4-amino-1,8
      naphthalimido)propyl (4A-NAIP), 3-(3-nitro-1,8-naphthalimido)propyl (3N-NAIP),
      and 3-(4-nitro-1,8-naphthalimido)propyl modified silyl silica gel (4N-NAIP)] are
      prepared in a single reaction. Chromatographic properties of these phases are
      characterized using various solutes including monosubstituted benzenes, alkyl
      benzenes, and polycyclic aromatic hydrocarbons (PAHs) in high-performance liquid
      chromatography. Even though the retention in these NAIPs is mainly based on the
      reversed-phase mode, 3N- and 4N-NAIP show a remarkable recognition toward
      aromatic hydrocarbons, which is attributed to their strong pi-pi interaction.
      Furthermore, the recognition ability is according to the molecular planarity and
      non-linearity of PAHs. Subsequently, 3N- and 4N-NAIP has a distinct selectivity
      from octadecyl silica and, therefore, will be a valuable alternative for a
      separation or a solid-phase extraction of aromatic compounds.

PMID- 15842750
TI  - Capillary electrophoresis for diastereomers of (R,S)-tetrahydroisoquinoline-3
      carboxylic acid derivatized with (R)-4-nitro-7-(3-aminopyrrolidin-1-yl)-2,1,3
      benzoxadiazole: effect of molecular geometries.
AB  - Diastereomers derived from (R,S)-tetrahydroisoquinoline-3-carboxylic acid (Tic),
      a potential neurotoxin with a chiral fluorescence tagging reagent, (R)-4-nitro-7
      (3-aminopyrrolidin-1-yl)-2,1,3-benzoxadiazole (NBD-APy), are well resolved by
      capillary electrophoresis (CE). For a better understanding of the separation
      mechanism, a semiempirical computational method (i.e., AM1 method) is used to
      study the molecular geometry, relative energy, and size of the derivatives. The
      molecular sizes are estimated to be 216.3 and 240.6 cm3/mol for (R)-NBD-APy-(R)
      Tic and (R)-NBD-APy-(S)-Tic, respectively. The CE elution order of the
      diastereomeric derivatives confirms the AM1 computational results: (R)-NBD-APy
      (R)-Tic elutes before (R)-NBD-APy-(S)-Tic. The effects of running buffer pH and
      the addition of a chiral selector, beta-cyclodextrin (beta-CD), on the separation
      are studied. In the presence of beta-CD, the migration behavior of the
      diastereomers is changed because of the formation of CD inclusion complexes.
      Study of the space-filling models for optimized conformations of the
      diastereomeric derivatives and beta-CD suggests that the geometries of the
      diastereomers decides that the diastereomers are incorporated into the CD cavity
      to form CD inclusion complexes with different volumes. Experimental results from
      CE separations conclude the same.

PMID- 15842751
TI  - Adsorption-driven retention in normal-phase chromatography with ternary mobile
      phases.
AB  - The model for retention in chromatographic systems using ternary mobile phases is
      considered. The driving force for the separation is assumed to be only a
      difference in adsorptive properties of a solute and all solvents. The effects of
      mobile phase composition are discussed. A series of very simple dependences
      between parameters characterizing retention in ternary and binary solvents is
      presented. The linear relationship is proposed to predict the capacity factor in
      the ternary mobile phase, for which the ratio of mole fractions of two less-polar
      solvents remains fixed. Theoretical concepts are verified by comparing the
      calculated values with experimental data measured in the entire concentration
      region.

PMID- 15842752
TI  - A rapid LC-MS-MS method for the determination of nicotine and cotinine in serum
      and saliva samples from smokers: validation and comparison with a
      radioimmunoassay method.
AB  - The development and validation of a rapid liquid chromatography (LC)-tandem mass
      spectrometry (MS-MS) method for determination of nicotine and cotinine in
      smokers' serum is described. The method is based on solid-phase extraction in a
      96-well plate format and requires only 100 microL of serum. Using normal-phase
      chromatography, both analytes elute in less than 1 min, which permits high sample
      throughput applications. The calibrated range is 2-100 ng/mL nicotine and 20
      1,000 ng/mL cotinine. For known samples, recovery is 95-116% for nicotine and 93
      94% for cotinine. The method is extended to rat serum and human saliva (cotinine
      only) using partial validation techniques. When compared with an existing
      radioimmunoassay method in our laboratory, the LC-MS-MS method gives improved
      accuracy, precision, and sample throughput.

PMID- 15842753
TI  - Elution behavior for a large sample size of uranyl ions on reversed-phase columns
      using alpha-hydroxyisobutyric acid as an eluent.
AB  - Large sample sizes of uranyl ions are eluted on a strenedivinylbenzene copolymer
      phase and an octadecyl phase column, respectively, using alpha-hydroxyisobutyric
      acid (alpha-HiBA) as an eluent. Chromatograms are obtained from variations of the
      uranyl sample amounts, eluent concentrations, concentrations of the sample
      matrix, and the pH of the sample solution for both columns, respectively. Column
      capacities are estimated from the loading factors measured from the retention
      times of the peaks. Bandwidths of the peaks and apparent column efficiencies are
      measured as a function of the loading factor and calculated using the equations
      derived from the assumptions of a Langmuir isotherm for a single solute.
      Comparison between the experiment and the calculation reveals that the former
      showed a broader bandwidth and worse column efficiency than the latter for both
      columns. The two columns are compared with regards to the retention time, peak
      shape, column capacity, column efficiency, etc. The PRP-1 column shows a
      rectangular-, triangle-type peak shape, longer retention time, lower column
      capacity, and better column efficiency, and the LC-18 column shows a distorted
      Gaussian curve, shorter retention time, higher column capacity, and worse column
      efficiency. Column capacity, peak shape, and retention time are dependent on the
      eluent concentration rather than the alpha-HiBA concentration in the sample
      solutions.

PMID- 15842754
TI  - Ecdysteroid glycosides: identification, chromatographic properties, and
      biological significance.
AB  - Ecdysteroid glycosides are found in both animals and plants. The chromatographic
      behavior of these molecules is characteristic, as they appear much more polar
      than their corresponding free aglycones when analyzed by normal-phase high
      performance liquid chromatography (HPLC), whereas the presence of glycosidic
      moieties has a very limited (if any) impact on polarity when using reversed-phase
      HPLC. Biological activity is greatly reduced because the presence of this bulky
      substituent probably impairs the interaction with ecdysteroid receptor(s). 2
      Deoxy-20-hydroxyecdysone 22-O-beta-D-glucopyranoside, which has been isolated
      from the dried aerial parts of Silene nutans (Caryophyllaceae), is used as a
      model compound to describe the rationale of ecdysteroid glycoside purification
      and identification.

PMID- 15842755
TI  - A new analysis method with GC or GC-MS for the quick detection of pesticide
      residues in vegetables.
AB  - A new analytical method for gas chromatography (GC) or GC-mass spectrometry (MS)
      using the direct sampling technique is described. This direct sampling technique,
      which bypasses the conventional complicated sample pretreatment process, is
      applicable to cases of fast detection of pesticide residues in foods and large
      scale screening of samples by portable GC in field detection. By a direct
      sampling technique, the vegetable sample is ground into paste, and 30 mg is
      placed directly into the evaporating chamber for GC-MS identification and
      quantitation (by full-scan mode). The GC column used is an HP-5 (30.0-m x 250
      microm x 0.25-microm, 5% phenyl methyl siloxane). Chlorpyrifos, bromophos,
      fenpropathrin, gamma-666, and pp'-DDT are chosen to represent organophosphorus,
      pyrethrins, and organochlorine pesticides because they are chief objects of the
      detection of pesticide residues in vegetables. Rape, a common and mass-consumed
      vegetable in China, is chosen as the sample in this study. The detection limits
      for these pesticides by the full-scan mode are all below the maximum pesticide
      residue limit of vegetables set by the Ministry of Agriculture of China, and the
      reproducibility of this method is acceptable. This analysis method is proven to
      be simple, quick, and reliable and is suitable for multipesticide residues
      analysis of vegetables. It can also be used in the analysis of vegetable
      components and signal chemicals.

PMID- 15842756
TI  - Quantification of ricinine in rat and human urine: a biomarker for ricin
      exposure.
AB  - Ricin is a toxalbumin derived from the castor bean plant, Ricinus communis.
      Ricinine is an alkaloid (3-cyano-4-methoxy-N-methyl-2-pyridone) that shares a
      common plant source with ricin, and its presence in urine infers ricin exposure.
      A new quantification method for ricinine was developed that uses solid-phase
      extraction to prepare 1-mL urine samples (81% recovery) for a 5-min, isocratic
      high-performance liquid chromatography method, followed by electrospray
      ionization tandem mass spectrometry. Protonated molecular ions were selected in
      the multiple reaction monitoring mode and quantified by isotope dilution with
      (13)C(6)-labelled ricinine as the internal reference. Urine pools enriched with
      ricinine at two concentrations were characterized as quality control materials
      and then used to validate the method. The method limit of quantification was
      0.083 ng/mL, even with a confirmation ion of low relative abundance. Ricinine was
      stable in human urine when heated at 90 degrees C for 1 h, and during storage at
      25 degrees C and 5 degrees C for 3 weeks. The method was applied to an animal
      exposure study, a crude ricin preparation scheme, and a forensic analysis. These
      studies show that ricinine can be measured in rat urine at least 48 h after
      exposure. Ricinine is present in crude preparations of ricin, and it can be found
      in human urine after a lethal exposure to ricin.

PMID- 15842757
TI  - Rapid bioassay for the determination of dioxins and dioxin-like PCDFs and PCBs in
      meat and animal feeds.
AB  - Over the past several years, the numerous contamination incidents have raised
      concerns over the presence of halogenated aromatic hydrocarbons, such as 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), and related chemicals in foods and feeds.
      Here we applied a sensitive recombinant mouse hepatoma cell (H1L1.1c2) bioassay
      for the determination of dioxins and dioxin-like polychlorinated dibenzofurans
      (PCDFs) and biphenyls (PCBs) in meat and animal feeds. These cells responded to
      TCDD-like chemicals with dose-dependent induction of firefly luciferase activity,
      and the minimal detection limit of TCDD in the cell was 16 fg. Induction
      equivalency factors determined for pure TCDD-like polychlorinated dibenzo-p
      dioxins (PCDDs), PCDFs, and PCBs in the bioassay were well-correlated with the
      World Health Organization's toxic equivalency factors. To determine the
      applicability of the bioassay system to detect those compounds presence in meat
      and feed samples, cell bioassays for 17 TCDD-like PCDDs and PCDFs congeners
      spiked lipid extracted from beef or animal feed were performed. Mean recoveries
      of TCDD-like chlorinated PCDDs and PCDFs congeners from spiked beef or feed fat
      ranged from 61.2 to 122.3%. Within-laboratory coefficients of variation for
      analysis as index of precision were lower than 5.2%, and the calculated limits of
      detection and quantitation were 0.33 and 1 pg toxicity equivalency quantity
      (TEQ)/0.5 g fat, respectively. Correlation between bioassay- and high-resolution
      gas chromatography-mass spectrometry (HR-GC-MS)-determined TEQs for 10 meat
      samples was 0.85, with 1.2 times higher in bioassay than HR-GC-MS. The
      correlation between bioassay- and HR-GC-MS-determined TEQs in 10 animal feed
      products was 0.81, with 2.1 times higher in bioassay than HR-GC-MS. Overall,
      these results demonstrated that the recombinant cell bioassay can be used for the
      rapid detection and quantitation of PCDDs and dioxin-like PCDFs and PCBs in meats
      and animal feeds.

PMID- 15842758
TI  - Detection of ketamine and norketamine in urine of nonhuman primates after a
      single dose of ketamine using microplate enzyme-linked immunosorbent assay
      (ELISA) and NCI-GC-MS.
AB  - The general anesthetic ketamine (Ketalar, Ketaject, Vetalar) (KET) is used in
      human and veterinary medicine for induction of anesthesia for short surgical
      procedures and routine veterinary examination. Its illicit use by teenagers in
      rave parties has been reported, and it has recently been identified as a
      substance associated with sexual assault. One aim of this paper was to study the
      elimination of KET and its major metabolite norketamine (NKET) in urine collected
      from five nonhuman primates that received a single dose (5 mg/kg, I.M.) of KET
      and to study elimination patterns to determine how long after drug administration
      KET and NKET can be detected. Another aim of this study was to develop and
      validate a highly sensitive negative ion chemical ionization-gas chromatography
      mass spectrometry (NCI-GC-MS) method for the simultaneous quantitation of KET and
      its major metabolite NKET in urine and to analyze urine samples collected from
      the animals. The last aim of this study was to apply and evaluate a newly
      developed ELISA screening methodology for detection of KET and its metabolites in
      the same urine samples collected from primates which received a single dose of
      KET. In two monkeys, KET was detected in urine up to 3 days after drug
      administration (32-7070 ng/mL); in one monkey, it was detected up to 4 days (65
      13,500 ng/mL); in one monkey, it was detected only on days 1 and 2 (4000 and 70
      ng/mL, respectively); and in one monkey, it was detected 10 days after KET
      injection (22-35,000 ng/mL). NKET concentrations ranged from 63 pg/mL to 1.75
      microg/mL, and it remained in the urine throughout the entire 35-day study period
      in 4 out of 5 animals. In one monkey, NKET was detected up to 31 days after KET
      administration. Urine analysis using ELISA revealed that KET and NKET can be
      easily detectable at 25 ng/mL. In one monkey, KET and its metabolites were
      detected in urine up to 4 days after drug administration, up to 7 days in two
      monkeys, up to 11 days in one monkey, and 16 days after KET injection in one
      monkey. Urine extraction followed by screening using ELISA methodology allowed
      for significant extension of the detection period in all animals from the study.
      It is believed that the KET elimination in urine of nonhuman primates is slightly
      faster than in humans. We propose that NCI-GC-MS be employed to detect NKET as a
      target compound in urine in toxicological investigations of drug-facilitated
      sexual assault when KET use by the perpetrator is suspected.

PMID- 15842759
TI  - Determination of nalmefene by high-performance liquid chromatography-electrospray
      ionization-tandem mass spectrometry.
AB  - Nalmefene is an opioid antagonist used in the treatment of alcoholism and opioid
      overdose. A highly sensitive method was developed to measure nalmefene in human
      and rabbit plasma and rabbit serum. Nalbuphine was used as internal standard.
      Liquid-liquid extraction was applied using n-butyl chloride/acetonitrile (4:1).
      High-performance liquid chromatography interfaced by electrospray ionization to a
      tandem mass spectrometer was used for quantitation. Primary validation
      experiments were conducted using human plasma then it was cross-validated in
      rabbit plasma and rabbit serum. Specificity (peak-area ratio of blank plasma or
      serum to its internal standard as percent of peak-area ratio of blank plasma or
      serum fortified with 0.1 ng/mL nalmefene to its internal standard) ranged from
      2.09 to 5.29 with a mean of 3.21% for human plasma and from 4.08 to 6.63 with a
      mean of 5.55% for rabbit plasma and from 2.47 to 6.17 with a mean of 3.62% for
      rabbit serum. The mean recovery for nalmefene was 80% in human plasma. The
      calibration range was from 0.1 to 100 ng/mL. Intrarun accuracy of the lower limit
      of quantitation (0.1 ng/mL) in all matrices was within 18.0% of target with
      intrarun precision within 13.6%. At 0.3, 35, and 75 ng/mL, the intrarun accuracy
      in all matrices was within 11.9% of target with intrarun precision within 6.6%.
      The inter-run accuracy in human plasma was within 8.0% of target with inter-run
      precision within 6.6%. Nalmefene was stable in human and rabbit plasma and rabbit
      serum for up to 24 h at room temperature and in human plasma after three freeze
      thaw cycles. Following intravenous injection of 5 mg/kg nalmefene to rabbits, the
      mean area under curve for 0 to 24 h was 1116 (ng)(mL)(-1)(h), and the mean plasma
      clearance was 67.9 (mL)(min)(-1)(kg)(-1).

PMID- 15842760
TI  - Determination of phenanthrene and hydroxyphenanthrenes in various biological
      matrices at trace levels using gas chromatography-mass spectrometry.
AB  - A fast and efficient multiresidue extraction-purification procedure was developed
      for low levels (ppb range) of phenanthrene and hydroxyphenanthrene in biological
      matrices, in order to quantify phenanthrene and metabolites in blood, milk,
      urine, and biological tissues of lactating goats. Detection and identification of
      the analytes (phenanthrene and 1-, 2-, 3-, 4-, and 9-hydroxyphenanthrene) were
      achieved using gas chromatography coupled to mass spectrometry. Deuterium-labeled
      phenanthrene was used as internal standard for phenanthrene and 2-OHfluorene for
      metabolites. The developed method includes enzymatic hydrolysis, liquid-liquid
      extraction, and Envi-Chrom P SPE column purification. Analyses were performed in
      the selected ion monitoring mode to achieve ad hoc sensitivity in accordance with
      analyte concentrations in food samples. Detection limits were between 2.3 and 5.1
      ng/mL (ppb) for milk samples, 0.5 and 2.5 ng/mL for urine and blood samples, and
      1.9 and 8.0 ng/g for tissue samples. This original multiresidue and multimatrix
      analytical methodology was applied to metabolism studies and polycyclic aromatic
      hydrocarbon (PAH) risk assessment. We demonstrated, for the first time, that
      metabolites were present in milk. These results suggested that usual PAHs
      analysis methods based on the detection of native molecule are not representative
      of the real contamination of biological matrices.

PMID- 15842761
TI  - Comparison of UV, fluorescence, and electrochemical detectors for the analysis of
      formaldehyde-induced DNA adducts.
AB  - A high-performance liquid chromatography (HPLC) method for normal and
      formaldehyde-modified deoxynucleosides after hydrolysis of exposed and unexposed
      human placental DNA was compared with ultraviolet (UV), fluorescence (FL), and
      electrochemical (EC) detectors. The lower quantifiable limits (LQL) for UV
      detection at 254 nm were 10-22 pmol for N(6)-hydroxymethyldeoxyadenosine (N(6)
      dA), N(2)-hydroxymethyldeoxyguanosine (N(2)-dG), and N(4)
      hydroxymethyldeoxycytidine (N(4)-dC), with N(4)-dC having the highest LQL and the
      2 purines the lowest LQL. Similarly, LQLs using FL (excitation: 264 nm; emission:
      340 nm) were 14-30 pmol, with N(2)-dG having the lowest LQL and N(6)-dA the
      highest. The LQL for N(2)-dG by EC detection at +1.10 V was 27 pmol, over 50-fold
      greater sensitivity than for the other hydroxymethyl deoxynucleosides;
      deoxyguanosine was similarly detected more sensitively than the other normal
      deoxynucleosides. Percent relative standard deviations ranged between 6 and 13%
      for both intra- and interrun assays for all detectors. HPLC-UV allows all the
      deoxynucleosides to be detected without the flow cell washing and use of fresh
      solutions necessary for the more selective FL detection, the latter not having
      enzyme blank interferences. EC allows only deoxyguanosine and N(2)-dG to be
      detected at pmol levels with no blank interferences. HPLC-UV allowed more
      sensitive detection of N(2)-dG and N(6)-dA than the other techniques and is
      recommended. The UV, FL, and EC properties of the hydroxymethyl deoxynucleosides
      of dA, dG, and dC are reported for the first time.

PMID- 15842762
TI  - Quantification of 2,4-D on solid-phase exposure sampling media by LC-MS-MS.
AB  - Three types of solid-phase chemical exposure sampling media: cellulose,
      polyurethane foam, and XAD-2, were analyzed for 2,4-dichlorophenoxyacetic acid
      (2,4-D) and the amine salts of 2,4-D. Individual samples were extracted into
      acidified methanol, and the extracts were analyzed via liquid chromatography
      tandem mass spectrometry using electrospray ionization and a C(8) reversed-phase
      LC column. (13)C 2,4-D and a labeled benzoic acid (13)C or d5) were employed as
      the surrogate and internal standard, respectively. Over a three-year study of
      pesticide exposure among agricultural workers involving a high volume of
      analyses, values of average % recovery for (13)C 2,4-D on personal exposure
      samples ranged from 87 to 98 with a % relative standard deviation ranging from 7
      to 12. The performance of the method compares favorably with that of the current
      National Institute for Occupational Safety and Health-recommended approach for
      the analysis of 2,4-D on these types of exposure sampling matrices.

PMID- 15842763
TI  - Urine benzodiazepine screening using Roche Online KIMS immunoassay with beta
      glucuronidase hydrolysis and confirmation by gas chromatography- mass
      spectrometry.
AB  - Performance of the Roche Online KIMS (kinetic interaction of microparticles in
      solution) benzodiazepine (BZD) immunoassay (IA) with and without beta
      glucuronidase treatment was evaluated on a Hitachi Modular automated IA analyzer
      calibrated using nordiazepam at 100 ng/mL. Reproducibility, linearity, accuracy,
      sensitivity, and interferences were evaluated. Precision of the assay (percent
      coefficient of variation (%CV)) with and without addition of the enzyme was less
      than 6% and 9%, respectively, with linearity (r(2) value of 0.9578 and 0.9746),
      respectively. Between-run precision of a 125 ng/mL nordiazepam control (n = 287)
      over 67 days, produced a %CV of 13.6% for the hydrolytic assay. Modification of
      the BZD assay to include automated hydrolysis of urinary BZD glucuronide
      conjugates was evaluated using three glucuronidated BZD standards prepared at
      concentrations ranging from 250 to 10,000 ng/mL. With hydrolysis, temazepam,
      oxazepam, and lorazepam glucuronides, produced cross-reactivities of 25%, 15%,
      and 20%, respectively. Without hydrolysis, the glucuronidated BZD standards
      produced less than 1% cross-reactivity in the assay. The ability of the assay to
      differentiate between positive and negative samples was evaluated by assaying 20
      negative urine samples and serial dilutions of certified drug-free urine
      fortified with 28 different BZDs. All of the negative and positive urine samples
      produced the appropriate screening result. Cross-reactivities of 27 different
      BZDs, calculated as the normalized IA response divided by the BZD concentration
      that produced a response approximately equivalent to the response of a 100 ng/mL
      nordiazepam standard and multiplied by 100, ranged from 15% to 149%. Human urine
      samples (n = 28) that were previously found to contain BZDs by gas chromatography
      mass spectrometry (GC-MS) also produced a positive BZD IA result. The IA was
      challenged with 78 potentially interfering compounds, and none produced a
      positive BZD response. As a part of the validation, a large number of human urine
      samples (29,500) were assayed using the modified Online BZD IA method to evaluate
      the performance of the method in production. Of the 29,500 samples tested, 80
      produced a positive IA result. Analysis by GC-MS confirmed the presence of at
      least 1 BZD compound in 61 of the samples corresponding to a confirmation rate of
      76%. The Online BZD IA modified by the automatic addition of beta-glucuronidase
      appears well adapted for the rapid detection of BZDs and their metabolites in
      human urine.

PMID- 15842764
TI  - Evaluation of the Cedia heroin metabolite (6-AM) immunoassay with urine specimens
      from A criminal justice drug-testing program.
AB  - The ability to differentiate illicit from legitimate drug use in a drug-testing
      program would decrease costs by reducing the number of screening specimens
      requiring confirmation and also reduce the stigma attached to positive
      preliminary test results. Because many screening tests for drug detection use
      immunoassays, increasing the specificity of these tests has been a goal of
      manufacturers. In this study we evaluated the utility of one such assay, the
      Cedia heroin metabolite (6-acetylmorphine, 6-AM) assay to reliably detect heroin
      use. Specimens (N = 525) from a criminal justice drug-testing program were
      screened with this assay (cutoff concentration = 10 ng/mL 6-AM) and any positive
      samples were confirmed by gas chromatographic-mass spectrometric analysis (lower
      reporting limit for 6-AM = 5 ng/mL). The confirmation rate for the enzyme
      immunoassay (EIA) was 98% (517/525). Specimens contained 6-AM at concentrations
      ranging from 5 to 16,923 ng/mL (mean = 1251; median = 317). All confirmed
      specimens also contained morphine (range: 8-222,427 ng/mL; mean = 11,203 ; median
      = 4134). When challenged with standard drug solutions, the EIA correctly
      identified drug-free urine and produced positive results (lowest concentration,
      in ng/mL, that produced a positive result) with morphine at 10,000; oxycodone at
      61,000; codeine at 60,000; hydromorphone at 10,000; hydrocodone at 60,000, 6-AM
      at 10, and pentazocine at 35,000 ng/mL. The Cedia heroin metabolite (6-AM) assay
      produced a high confirmation rate when challenged with urine specimens and
      therefore should be a useful tool in forensic toxicology. Potential users should
      be aware that high concentrations of other opioids (e.g., morphine, oxycodone)
      and structurally related compounds (e.g., pentazocine) may produce positive
      results.

PMID- 15842765
TI  - Stability of barbiturates in fixed tissues and formalin solutions.
AB  - This study reports the results of the retention and quantitation of barbiturates
      in fresh tissue, in liver tissue fixed in formalin, and in the formalin solutions
      in which the same tissues were fixed for six months. Biological materials came
      from four cases of death due to phenobarbital and two due to butalbital. Results
      showed the presence of barbiturates in all studied materials. Mean recovery rates
      of phenobarbital in fixed liver were 57.11% and 30.84% in formalin from liver;
      and those of butalbital in fixed liver were 21.66% and 66.56% in formalin from
      liver. Total sums of recovery rates in formalin solutions and fixed tissues for
      phenobarbital (87.95%) and butalbital (88.22%) were comparable with those of the
      extraction efficiency of the method (90.2%) and indicate that these barbiturates
      have good stability even in biological specimens subjected to chemical fixation.
      This fact may be useful in qualitative evaluation of cases.

PMID- 15842766
TI  - Telomere and telomerase as targets for anti-cancer and regeneration therapies.
AB  - Telomerase is a ribonucleoprotein that directs the synthesis of telomeric
      sequence. It is detected in majority of malignant tumors, but not in most normal
      somatic cells. Because telomerase plays a critical role in cell immortality and
      tumor formation, it has been one of the targets for anti-cancer and regeneration
      drug development. In this review, we will discuss therapeutic approaches based
      mainly on small molecules that have been developed to inhibit telomerase
      activity, modulate telomerase expression, and telomerase directed gene therapy.

PMID- 15842767
TI  - Effects of melatonin on wortmannin-induced tau hyperphosphorylation.
AB  - AIM: To explore the underlying mechanism of tau hyperphosphorylation in an
      Alzheimeros-affected brain and the possible arresting strategies. METHODS: MTT(3
      [4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide), crystal violet
      assay, phase-contrast, dead end colorimetric apoptosis detection system (TUNEL)
      and electron microscopy were used to detect cell viability, morphology and
      apoptosis. Western blot, 32P-labeling and the detection of malondialdehyde level
      and superoxide dismutase activity were used respectively for the phosphorylation
      level of tau, the activity of glycogen synthase kinase (GSK-3), and oxidative
      stress measurement. RESULTS: Exposure of the cells to wortmannin resulted in an
      obvious lipid peroxidation, reduction of cell viability, cell process retraction,
      and plasma vacuolation, but with no obvious cell apoptosis. We also found that
      preincubation of the cells with melatonin or vitamin E attenuated differentially
      wortmannin-induced oxidative stress as well as GSK-3 overactivation and tau
      hyperphosphorylation. CONCLUSION: Wortmannin is an effective tool for reproducing
      Alzheimer-like tau hyperphosphorylation cell model and melatonin/vitamin E can
      effectively protect the cells from wortmannin-induced impairments.

PMID- 15842768
TI  - Pharmacological profiles of an anticholinergic agent, phencynonate hydrochloride,
      and its optical isomers.
AB  - AIM: To comparatively study the pharmacological profiles of 3-methyl-3
      azabicyclo(3,3,1)nonanyl-9-alpha-yl-alpha-cyclopentyl-alpha-phenyl-alpha
      glycolate (phencynonate hydrochloride, CPG), an anticholinergic agent, and its
      enantiomers [R(-)-and S(+)-CPG]. METHODS: The affinity and relative efficacy were
      tested using radioligand-binding assay with muscarinic acetylcholine receptors
      from rat cerebral cortex. The pharmacological activities were assessed in three
      individual experiments: (1) potentiating the effect of subthreshold hypnotic dose
      of sodium pentobarbital; (2) inhibiting oxotremorine-induced salivation; and (3)
      inhibiting the contractile response to carbachol. RESULTS: The order of potency
      of phencynonate hydrochloride and its optical isomers to inhibit the binding of
      [3H]quinuclidinyl benzilate ([3H]QNB) was R(-)-CPG (K(i)=46.49+/-1.27
      nmol/L)>CPG(K(i)=271.37+/-72.30nmol/L)>S(+)-CPG(K(i)=1263.12+/-131.64 nmol/L).
      The results showed that R(-)-CPG had the highest affinity to central muscarinic
      receptors among the three compounds, but did not show any central depressant
      effects at dose from 10.00 to 29.15 mg/kg. CPG increased the effects of
      subthreshold hypnotic dose of sodium pentobarbital induced-sleeping [the ED50+/
      95% LC value was 21.06+/-3.04 mg/kg]. CPG and R(-)-CPG displayed nearly
      equipotent effect in depressing oxotremorine-induced salivation [the ED50 +/-95%
      LC for R(-) and CPG were 1.10+/-0.28 and 1.07+/-0.15 mg/kg, respectively], and
      the contractile response to carbachol (pA(2) values for R (-) and CPG were 6.84
      and 6.80, respectively). S(+)-CPG presented the lowest anticholinergic profiles,
      but could potentate effects of its enantiomers in some manner. CONCLUSIONS: These
      data suggested that R(-)-CPG acted as an eutomer in racemate and a competitive
      antagonist to acetylcholine muscarinic receptors, but S(+)-CPG was less active in
      comparison to R(-)-CPG and its racemate. The central depressant effects of R(-)
      CPG and S(+)-CPG were lower in comparison to its racemate.

PMID- 15842769
TI  - Effects of l-tetrahydropalmatine on locomotor sensitization to oxycodone in mice.
AB  - AIM: Recent studies have shown that l-tetrahydropalmatine (l-THP), an active
      component of Corydolis yanhusuo, can inhibit the development of the conditional
      place preference induced by opioid receptor agonists, but the effects of l-THP on
      locomotor sensitivity induced by opioid receptor agonists have not been
      documented. In the present study, the effects of l-THP on locomotor sensitization
      to oxycodone, which is an opioid receptor agonist, were studied. METHODS: Mice
      treated daily for 7 d with 5 mg/kg oxycodone and challenged with the same dose
      after 5 days of washout showed locomotor sensitization. In order to study the
      effects of l-THP on locomotor sensitization induced by oxycodone, l-THP was
      administered at doses of 6.25, 12.5, and 18.75 mg/kg, 40 min prior to treatment
      of oxycodone. RESULTS: l-THP per se did not affect the locomotor activity at the
      doses of 6.25, 12.5, and 18.75 mg/kg, but could antagonize the hyperactivity
      induced by oxycodone (5 mg/kg). Co-administration of l-THP (18.75 mg/kg), 40 min
      prior to oxycodone, could inhibit the development of sensitization to oxycodone.
      In addition, l-THP (6.25, 12.5, and 18.75 mg/kg, i.g.) dose-dependently prevented
      the expression of oxycodone sensitization. CONCLUSION: These results suggested
      that l-THP could attenuate the locomotor-stimulating effects of oxycodone and
      inhibit the development and expression of oxycodone behavioral sensitization.

PMID- 15842770
TI  - Action of aluminum on high voltage-dependent calcium current and its modulation
      by ginkgolide B.
AB  - AIM: To investigate the effect of aluminum (Al) on high voltage-dependent calcium
      current (I(HVA)) and its modulation by ginkgolide B (Gin B). METHODS: The whole
      cell, patch-clamp technique was used to record IHVA from acutely isolated
      hippocampal CA1 pyramydal neurons in rats. RESULTS: Al 0.1 mmol/L (low
      concentration) reduced I(HVA); Al 0.75 and 1.0 mmol/L (high concentrations)
      increased I(HVA), and Al decreased and increased I(HVA) at intermediate
      concentrations of 0.25 and 0.5 mmol/L. The increase of I(HVA) by Al 1.0 mmol/L
      was enhanced by the adenylyl cyclase (AC) agonist forskolin and was partly
      abolished by the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A
      (PKA) antagonist H-89, whereas the decrease observed with Al 0.1 mmol/L was
      neither reversed by forskolin nor affected by H-89. Gin B had no effect on I(HVA)
      in normal neurons, but canceled the increase in I(HVA) by 1.0 mmol/L Al.
      CONCLUSION: The results indicate that the mechanism of Al affecting I(HVA)
      differs at different concentrations, and this may be attributed to its complex
      actions. Gin B could prevent neurons from injury by inhibiting calcium influx.

PMID- 15842771
TI  - Remifentanil mimics cardioprotective effect of ischemic preconditioning via
      protein kinase C activation in open chest of rats.
AB  - AIM: To examine whether the protective effect of remifentanil preconditioning
      (RPC) on postischemic hearts is mediated by protein kinase (PKC) activation in
      comparison with ischemic preconditioning (IPC). METHODS: Male Sprague-Dawley rats
      were anesthetized and their chests were opened. The experiment was performed with
      chelerythrine (CHE, 2 mg/kg), GF109203X (0.05 mg/kg) protein kinase C (PKC)
      inhibitors administered before RPC (remifentanil 6 microg x kg(-1) x min(-1) x 3
      cycle) or IPC, respectively. Infarct size (IS), as a percentage of the area at
      risk (AAR), was determined by triphenyltetrazolium staining. RESULTS: In groups
      subjected to IPC and RPC the IS/AAR were significantly reduced (IS/AAR from
      52.7%+/-5.5% to 12.9%+/-3.4%, P<0.01 vs CON and 16.2%+/-6.4%, P<0.01 vs CON),
      respectively. CHE and GF, both PKC inhibitors, administered 5 min before RPC or
      IPC completely abolished the cardioprotective effect of RPC (IS/AAR: CHE+RPC
      51.2%+/-5.0%, GF+RPC 53.6%+/-6.1%, P>0.05 vs CON) or IPC (CHE+IPC 53.7%+/-4.3%,
      GF+IPC 54.1%+/-6.2%, P>0.05 vs CON). The difference was not significant in any of
      the hemodynamic parameters between control and treatment groups during ischemia
      and reperfusion. CONCLUSION: Remifentanil confers myocardial protection against
      ischemic injury through a mechanism that is similar to IPC and involves PKC
      activation.

PMID- 15842772
TI  - Modulating effect of ginseng saponins on heterologously expressed HERG currents
      in Xenopus oocytes.
AB  - AIM: To examine the effects of ginseng saponins on the heterologously expressed
      human ether-a-go-go related gene (HERG) that encodes the rapid component of the
      delayed rectifier K+ channel. METHODS: A two-electrode voltage clamp technique
      was used. HERG currents were recorded in Xenopus oocytes injected with HERG cRNA.
      RESULTS: Crude saponins of Korean red ginseng (GS) induced a minimal increase of
      the maximal HERG conductance without changes in the voltage-dependent HERG
      current activation and inactivation curves. GS, however, decelerated HERG current
      deactivation in a concentration-dependent manner, which was more noticeable with
      panaxitriol (PT) than panaxidiol (PD). Consistently, ginseng saponins increased
      the HERG deactivation time constants with the order of potency of Rg1 (a major
      component of PT)>Rf1>Rb1 (a major component of PD). Re had little effect on HERG
      deactivation. During a cardiac action potential, GS increased the outward HERG
      current. CONCLUSION: Ginseng saponins enhance HERG currents, which could be in
      part a possible mechanism of the shortening cardiac action potential of ginseng
      saponins.

PMID- 15842773
TI  - Effects of AMP579 and adenosine on L-type Ca2+ current in isolated rat
      ventricular myocytes.
AB  - AIM: To compare the effects of AMP579 and adenosine on L-type Ca2+ current (I(Ca
      L)) in rat ventricular myocytes and explore the mechanism by which AMP579 acts on
      I(Ca-L). METHODS: I(Ca-L) was recorded by patch-clamp technique in whole-cell
      configuration. RESULTS: Adenosine (10 nmol/L to 50 micromol/L) showed no effect
      on basal I(Ca-L), but it inhibited the I(Ca-L) induced by isoproterenol 10 nmol/L
      in a concentration-dependent manner with the IC(50) of 13.06 micromol/L. Similar
      to adenosine, AMP579 also showed an inhibitory effect on the I(Ca-L) induced by
      isoproterenol. AMP579 and adenosine (both in 10 micromol/L) suppressed
      isoproterenol-induced ICa-L by 11.1% and 5.2%, respectively. In addition, AMP579
      had a direct inhibitory effect on basal I(Ca-L) in a concentration-dependent
      manner with IC50 (1.17 micromol/L). PD116948 (30 micromol/L), an adenosine A1
      receptor blocker, showed no action on the inhibitory effect of AMP579 on basal
      I(Ca-L). However, GF109203X (0.4 micromol/L), a special protein kinase C (PKC)
      blocker, could abolish the inhibitory effect of AMP579 on basal I(Ca-L). So the
      inhibitory effect of AMP579 on basal I(Ca-L) was induced through activating PKC,
      but not linked to adenosine A1 receptor. CONCLUSION: AMP579 shows a stronger
      inhibitory effect than adenosine on the I(Ca-L) induced by isoproterenol. AMP579
      also has a strong inhibitory effect on basal I(Ca-L) in rat ventricular myocytes.
      Activation of PKC is involved in the inhibitory effect of AMP579 on basal I(Ca-L)
      at downstream-mechanism.

PMID- 15842774
TI  - 5-Hydroxytryptamine-induced proliferation of pulmonary artery smooth muscle cells
      are extracellular signal-regulated kinase pathway dependent.
AB  - AIM: To investigate the effect of 5-hydroxytryptamine transporter (5-HTT)
      inhibitor fluoxetine and antisense oligodeoxynucleotide (ODN) to extracelluar
      signal-regulated kinases (ERKs) on pulmonary arterial smooth muscle cells
      (PASMCs) proliferation induced by 5-HT. METHODS: Liposomal transfection was used
      to introduce ODNs to ERK1/2 into cultured rat PASMCs and the transfection
      efficiency was measured by observing the uptake of the fluorecein isothiocynate
      (FITC)-labeled antisense ODN in PASMCs. The effects of 5-HTT selective inhibitor
      fluoxetine and ODNs on the proliferation of PASMCs were evaluated by cell number
      counting and cell cycle analysis, and measured by microculture tetrazolium (MTT)
      assay and flow cytometry (FCM), respectively. RESULTS: Liposomes mediated the
      transfection of ODNs into PASMCs with high efficiency. MTT assay showed
      fluoxetine (10 micromol/L, 1 micromol/L, and 100 nmol/L) concentration
      dependently inhibited the proliferation of PASMCs induced by 5-HT (1 micromol/L)
      in vitro. The proliferation rate of PASMCs by 5-HT was significantly inhibited by
      pretreatment with ERK1/2 antisense ODN (0.2 micromol/L) from 251%+/-18% to 86%+/
      5% (P<0.01). Flow cytometric analysis of cell cycle distribution showed that the
      increase of 5-HT induced S phase fraction (SPF) and proliferation index (PI) were
      significantly inhibited by fluoxetine (1 micromol/L) or antisense ODN with SPF
      from 36%+/-4% to 26%+/-3% and 24%+/-4%, and PI from 34%+/-2% to 29%+/-2% and
      24%+/-2%, respectively. CONCLUSION: 5-HTT mediates the mitogenic effect of 5-HT
      on PASMCs and the proliferation of PASMCs induced by 5-HT is dependent on ERKs
      signal pathway.

PMID- 15842775
TI  - Activation of human tonsil and skin mast cells by agonists of proteinase
      activated receptor-2.
AB  - AIM: To investigate the effects of the agonists of proteinase activated receptor
      (PAR)-2, and histamine on degranulation of human mast cells. METHODS: Human mast
      cells were enzymatically dispersed from tonsil and skin tissues. The dispersed
      cells were then cultured with various stimuli, and tryptase and histamine levels
      in cell supernatants collected from challenge tubes were measured. RESULTS: PAR-2
      agonist peptide SLIGKV provoked a dose-dependent release of histamine from skin
      mast cells. It also induced tryptase release from tonsil mast cells. tc-LIGRLO
      appeared less potent than SLIGKV in induction of release of histamine and
      tryptase. Trypsin was able to induce a bell shape increase in tryptase release
      from tonsil mast cells. It was also able to induce a dose-dependent release of
      histamine from both tonsil and skin mast cells. The actions of trypsin on mast
      cells were inhibited by soy bean trypsin inhibitor (SBTI) or alpha1-antitrypsin
      (alpha1-AT). Time course study revealed that both stimulated tryptase or
      histamine release initiated within 10 s and reached their peak release between 4
      and 6 min. Pretreatment of cells with metabolic inhibitors or pertussis toxin
      reduced the ability of mast cells to release tryptase or histamine. CONCLUSION:
      It was demonstrated that the in vitro tryptase release properties of human tonsil
      and skin mast cells suggested a novel type of mast cell heterogeneity. The
      activation of mast cells by PAR-2 agonists indicated a self-amplification
      mechanism of mast cell degranulation.

PMID- 15842776
TI  - Pioglitazone can ameliorate insulin resistance in low-dose streptozotocin and
      high sucrose-fat diet induced obese rats.
AB  - AIM: To investigate the effect of the peroxisome proliferator-activator receptor
      (PPAR)-gamma agonist, pioglitazone, on insulin resistance in low-dose
      streptozotocin and high sucrose-fat diet induced obese rats. METHODS: Normal
      female Wistar rats were injected intraperitoneally with low-dose streptozotocin
      (STZ, 30 mg/kg) and fed with a high sucrose-fat diet for 8 weeks. Pioglitazone
      (20 mg/kg) was administered orally to the obese and insulin-resistant rats for 28
      d. Intraperitoneal glucose tolerance tests, insulin tolerance tests and
      gluconeogenesis tests were carried out over the last 14 d. At the end of d 28 of
      the treatment, serums were collected for biochemical analysis. Glucose
      transporter 4 (GLUT4) and insulin receptor substrate-1 (IRS-1) protein expression
      in the liver and skeletal muscle were detected using Western blotting. RESULTS:
      Significant insulin resistance and obesity were observed in low-dose STZ and high
      sucrose-fat diet induced obese rats. Pioglitazone (20 mg/kg) treatment
      significantly decreased serum insulin, triglyceride and free fatty acid levels,
      and elevated high density lipoprotein-cholesterol (HDL-C) levels. Pioglitazone
      also lowered the lipid contents in the liver and muscles of rats undergoing
      treatment. Gluconeogenesis was inhibited and insulin sensitivity was improved
      markedly. The IRS-1 protein contents in the liver and skeletal muscles and the
      GLUT4 contents in skeletal muscle were elevated significantly. CONCLUSION: The
      data suggest that treatment with pioglitazone improves insulin sensitivity in low
      dose STZ and high sucrose-fat diet induced obese rats. The insulin sensitizing
      effect may be associated with ameliorating lipid metabolism, reducing
      hyperinsulinemia, inhibiting gluconeogenesis, and increasing IRS-1 and GLUT4
      protein expression in insulin-sensitive tissues.

PMID- 15842777
TI  - Inhibitory effects of idoxifene on hepatic fibrosis in rats.
AB  - AIM: To investigate the effects of a tissue-specific selective estrogen receptor
      modulator, idoxifene, on hepatic fibrosis in rats. METHODS: Hepatic fibrosis was
      induced by dimethylnitrosamine (DMN) in male rats. The DMN model of hepatic
      fibrosis and the hepatocytes undergoing oxidative stress were treated with
      idoxifene respectively. The effect of idoxifene on hepatic fibrosis in the DMN
      model was examined by immunohistochemistry. Effects of idoxifene on antioxidant
      enzyme levels of copper, zinc-dependent superoxide dismutase (CuZn-SOD), and
      cellular glutathione peroxidase (GSHPx) were measured by ELISA. Effects of
      idoxifene on activation, proliferation, and apoptosis of culture-activated
      hepatic stellate cells (HSC) were analysed by immunohistochemistry,
      bromodeoxyuridine (BrdU) uptake, and flow cytometry, respectively. RESULTS:
      Idoxifene could markedly suppress DMN-induced hepatic fibrosis in male rats. A
      treatment of 0.4 mg x kg(-1) x d(-1) of idoxifene reduced the protein levels of
      collagen in the DMN model by 41.19% (P<0.05). Protein level of CuZn-SOD and
      activitiy of GSHPx in liver treated with DMN plus 0.4 mg/kg/d of idoxifene were
      2.65 times (P<0.05) and 2.08 times greater (P<0.05) than that of liver treated
      with DMN alone respectively. The protein level of CuZn-SOD and activity of GSHPx
      in cultured rat hepatocytes treated with ferric nitrilotriacetate (FeNTA) plus 1
      multiply 10(-7) mol/L of idoxifene were 3.43 times (P<0.05) and 2.52 times
      (P<0.05) greater than that treated with FeNTA alone. Idoxifene could inhibit HSC
      activation. Compared with the control, the uptake of BrdU in HSC cultured with 1
      multiply 10(-7) mol/L of idoxifene was reduced by 51.87 % (P<0.05), and the
      number of apoptotic HSCs cultured with 1 multiply 10(-7) mol/L of idoxifene
      increased by 94.52% (P<0.05). CONCLUSION: Idoxifene showed inhibitory action on
      hepatic fibrosis in male rats.

PMID- 15842778
TI  - Effect of Oenanthe javanica flavone on human and duck hepatitis B virus
      infection.
AB  - AIM: To study the antiviral effect of Oenanthe javanica flavones (OjF) on human
      hepatoma HepG2.2.15 culture system and duck hepatitis B virus (DHBV) infection.
      METHODS: (1) After incubation for 24 h, the 2.2.15 cells were treated with
      different concentrations of OjF for 12 d. The cell alteration was observed by
      microscope. The presence of HBsAg and HBeAg were measured using the enzyme
      immunoassay kit after 2.2.15 cells were treated with OjF for 9 d. (2) Ducklings
      infected with DHBV intravenously were divided into 5 groups and treated with OjF,
      acyclovir (ACV), and normal saline respectively for 10 d. All the ducklings were
      bled before, during, and after treatments at different times, and serum levels of
      DHBV-DNA were detected by a dot-blot hybridization assay. RESULTS: (1) The 50%
      toxic concentration (TC50) of OjF was 2.28 g/L. The maximum nontoxic
      concentration (TC0) was 1.00 g/L. In nontoxic concentrations, OjF significantly
      inhibited HBsAg and HBeAg in 2.2.15 cells after 9 d of treatment (P<0.05,
      P<0.01). (2) The DHBV-DNA levels decreased significantly after the treatment with
      0.50 and 1.00 g/kg of OjF (P<0.01). The inhibition of the peak of viremia was
      maximum at a dose of 1.00 g/kg and reached 54.3% on d 5 and 64.5% on d 10,
      respectively. CONCLUSION: The results demonstrate that OjF is a strong inhibitor
      of HBsAg and HBeAg secretion in 2.2.15 cells and DHBV-DNA levels in the HBV
      infected duck model.

PMID- 15842779
TI  - The anti-endotoxic effect of o-aminobenzoic acid from Radix Isatidis.
AB  - AIM: To study the anti-endotoxic effect of o-aminobenzoic acid (OABA) isolated
      from Banlangen(BLG). METHODS: OABA was extracted and isolated from BLG and
      diluted into 0.5% solution. The concentration of endotoxin (ET) pretreated with
      OABA was quantitatively detected using Limulus test. The inhibition of ET-induced
      fever by OABA was measured in rabbits. The rates of lipopolysaccharides (LPS)
      induced death in mice pretreated with or without OABA were then compared. The
      influence of OABA on the release of TNF-alpha and NO from macrophages induced by
      LPS was examined in mice. RESULTS: After pretreatment with OABA, 84.4% of ET was
      destroyed. The ET-induced fever in rabbits decreased significantly and the rate
      of LPS-induced death in mice dropped from 70% to 20%. The release of TNF-alpha
      and NO induced by LPS in mice was inhibited dose-dependently when the
      concentration of OABA was between 0.125% and 0.5%. CONCLUSION: OABA isolated from
      BLG has an anti-endotoxic effect.

PMID- 15842780
TI  - Mycophenolate mofetil as a treatment for refractory idiopathic thrombocytopenic
      purpura.
AB  - AIM: To determine whether mycophenolate mofetil (MMF) has beneficial effects on
      refractory idiopathic thrombocytopenic purpura (ITP) and the corresponding
      cellular mechanism. METHODS: Twenty refractory ITP patients resistant to
      corticosteroid and/or splenectomy and chemical therapy were given MMF 1.5-2.0 g/d
      orally for a 2 to 4-month period. Serum immunoglobulin was detected by rate
      nephelometry. Platelet-associated antibodies (PAIgG) were assayed by enzyme
      linked immunosorbant assay. The immunophenotypic analysis was performed on a flow
      cytometer and cell apoptosis was detected with transferase mediated dUTP biotin
      nick end labeling (TUNEL) method. RESULTS: Sixteen of the 20 (80%) patients had
      responses to MMF treatment; 9 (45%) achieved a complete response, 4 (20%)
      achieved a partial response, and 3 (15%) achieved a minor response. The
      therapeutic effects were found to be better in male patients than female
      patients. The number of CD3+ peripheral blood cells (PBCs) and CD4+ PBCs
      increased and the number of CD8+ PBCs decreased. The plasma level of IgG, IgM,
      IgA and platelet associated IgG (PAIgG) decreased in 86% of the patients. TUNEL
      assay showed that mycophenolate acid (MPA) 0.1 mmol/L induced apoptosis of
      peripheral blood mononuclear cells isolated from refractory ITP patients. The
      apoptosis rate was increased in male patients after treatment with MPA, but was
      unchanged in female patients. CONCLUSION: Therapy for a period of 8 to 16 weeks
      with median-dose of MMF was valuable for the treatment of refractory ITP.

PMID- 15842781
TI  - Curcumin, a potent anti-tumor reagent, is a novel histone deacetylase inhibitor
      regulating B-NHL cell line Raji proliferation.
AB  - AIM: To investigate curcumin (diferuloylmethane) induced apoptosis and its
      molecular mechanism of action in B-NHL cell line Raji cells. METHODS: Raji cells
      were cultured in RPMI-1640 medium and treated with curcumin in different
      concentrations. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT)
      assay was used to detect growth inhibition and Hoechst 33258 staining was used to
      detect apoptosis. Immunocytochemistry and Western blot were used to detect the
      expressions of histone deacetylase 1, 3, and 8 (HDAC1, HDAC3, and HDAC8) and
      acetylated histone H4 (Ac-histone H4) protein. RESULTS: Curcumin inhibited the
      proliferation of B-NHL cell line Raji cells with a 36-h IC50 value of 24.1+/-2.0
      micromol/L. Hoechst 33258 staining showed that curcumin could induce Raji cell
      apoptosis. The expression levels of HDAC1, HDAC3, and HDAC8 proteins were
      downregulated following curcumin treatment in Raji cells, whereas Ac-histone H4
      protein expression was upregulated after treatment with curcumin. CONCLUSION:
      Curcumin, as a new member of the histone deacetylase inhibitors, can inhibit the
      expression of class I HDACs (HDAC1, HDAC3, and HDAC8), and can increase the
      expression of Ac-histone H4 in Raji cells. Curcumin plays an important role in
      regulating B-NHL cell line Raji cell proliferation and apoptosis.

PMID- 15842782
TI  - Transfection of promyelocytic leukemia in retrovirus vector inhibits growth of
      human bladder cancer cells.
AB  - AIM: To construct a recombinant retrovirus vector carrying human promyelocytic
      leukemia (PML) cDNA and identify its expression and biology role in bladder
      cancer UM-UC-2 cells for future gene therapy. METHODS: PML full-length cDNA was
      inserted into the EcoR I and BamH I site of pLXSN vector containing the long
      terminal repeat (LTR) promoter. The vector was identified by restriction enzyme
      digestion and then transfected into PA317 packaging cell line by calcium
      phosphate coprecipitation. PML cDNA was detected by polymerase chain reaction
      (PCR) and the protein was identified by laser confocal microscopy and Western
      blot in bladder cancer cells, respectively. The morphology was observed by
      inverted phase contrast microscope, and MTT assay determined growth curve of the
      bladder cancer cells. RESULTS: Restriction enzyme digestion proved that a 2.1 kb
      PML cDNA was inserted into the pLXSN vector. PCR assay demonstrated that 304 bp
      fragments were found in UM-UC-2/pLPMLSN transfects. Laser confocal microscopy
      showed speck dots fluorescence in the UM-UC-2/pLPMLSN nucleus. A 90 kD specific
      brand was found by Western blot. MTT assay demonstrated the UM-UC-2/pLPMLSN
      bladder cancer growth inhibition. CONCLUSION: The retrovirus pLPMLSN vector was
      successfully constructed and could generate high effective expression of human
      PML in bladder cancer cell UM-UC-2, suggesting that PML recombinant retrovirus
      have potential utility in the gene therapy for bladder cancer.

PMID- 15842783
TI  - Inhibitory effect of agmatine on proliferation of tumor cells by modulation of
      polyamine metabolism.
AB  - AIM: To assess the inhibitory effect of agmatine on tumor growth in vivo and
      tumor cell proliferation in vitro. METHODS: The transplanted animal model,
      [3H]thymidine incorporation assay,3-[4,5-dimethythiazol-2-yl]-2,5
      diphenyltetrazolium assay, and lactate dehydrogenase (LDH) release assay were
      performed. RESULTS: Agmatine, at doses of 5-40 mg/kg, suppressed the S180 sarcoma
      tumor growth dose-dependently in mice in vivo and the highest inhibitory ratio
      reached 31.3% in Kunming mice and 50.0% in Balb/c mice, respectively. Similar
      results were obtained in the transplanted B16 melanoma tumor model. Agmatine (1
      1000 micromol/L) was able to attenuate the proliferation of cultured MCF-7 human
      breast cancer cells in vitro in a concentration-dependent manner and the highest
      inhibitory ratio reached 50.3% in the [3H]thymidine incorporation assay.
      Additionally, in the LDH release assay, spermine (20 micromol/L) and spermidine
      (20 micromol/L) increased the LDH release significantly, but agmatine (1-1000
      micromol/L) did not, indicating that the inhibitory effect of agmatine on the
      proliferation of MCF was not related to cellular toxicity. In the [3H]thymidine
      incorporation assay, putrescine (12.5-100.0 micromol/L) could reverse the
      inhibitory effect of agmatine on the proliferation of MCF concentration
      dependently, suggesting that the inhibitory effect of agmatine on the
      proliferation of MCF might be associated with a decreased level of the
      intracellular polyamines pool. CONCLUSION: Agmatine had significant inhibitory
      effect on transplanted tumor growth in vivo and proliferation of tumor cells in
      vitro, and the mechanism might be a result of inducing decrease of intracellular
      polyamine contents.

PMID- 15842784
TI  - Induction of leukemia cell apoptosis by cheliensisin A involves down-regulation
      of Bcl-2 expression.
AB  - AIM: To investigate the apoptosis-inducing effect of cheliensisin A (GC-51), a
      novel styryl-lactone isolated from Goniothalamus cheliensis, on human
      promyelocytic leukemia HL-60 cells and the mechanism of action involved. METHODS:
      Apoptotic cell death was determined by morphological examination and DNA agarose
      gel electrophoresis. The activity of caspase-3 was assessed using Western
      blotting and the expression of Bcl-2 and Bax genes was analyzed using the reverse
      transcription-polymerase chain reaction (RT-PCR) method. RESULTS: GC-51
      significantly inhibited the proliferation of HL-60 cells with an IC50 of 2.4+/
      0.2 micromol/L and effectively induced apoptosis in HL-60 cells. Exposure of HL
      60 cells to 10 micromol/L GC-51 for 8 h resulted in approximately 53% of the
      cells undergoing apoptosis. Caspase-3 was activated in GC-51-treated cells, which
      was manifested by the appearance of the 17 kDa active form of caspase-3 and the
      cleavage of poly(ADP-ribose) polymerase (PARP). Meanwhile, GC-51 markedly reduced
      the expression of the anti-apoptotic gene Bcl-2 and increased the expression of
      the pro-apoptotic gene Bax. The apoptosis-inducing effect of GC-51 was cAMP
      dependent protein kinase (PKA) dependent because PKA, but not the protein kinase
      C, specific inhibitor H-89, blocked the induction of apoptosis by GC-51 in HL-60
      cells. CONCLUSION: The results demonstrate that GC-51 effectively induces
      apoptosis in HL-60 cells and that this effect is PKA-dependent and involves the
      downregulation of Bcl-2 expression and the activation of caspase-3.

PMID- 15842785
TI  - Antitumor effect of cytosine deaminase/5-fluorocytosine suicide gene therapy
      system mediated by Bifidobacterium infantis on melanoma.
AB  - AIM: To construct a Bifidobacterium infantis/CD targeting gene therapy system and
      observe the antitumor effect of cytosine deaminase/5-fluorocytosine (CD/5-FC)
      suicide gene therapy system mediated by Bifidobacterium infantis on melanoma in
      vitro and in vivo. METHODS: A recombinant CD/pGEX-1LamdaT plasmid was transfected
      into Bifidobacterium infantis by electroporation. Bifidobacterium infantis
      transfected by recombinant CD/pGEX-1LamdaT plasmid was incubated with 5-FC
      anaerobically. Then the supernatant fluid was collected and added to melanoma B16
      F10 cells to observe the killing effect for B16-F10 cells. Mice were inoculated
      with melanoma B16-F10 cells to establish animal models. The mice were then
      injected with 5-FC and Bifidobacterium infantis transfected by recombinant
      CD/pGEX-1LamdaT plasmid. RESULTS: Two segments of approximate 4.9 kb and 1.3 kb
      were extracted from the 6.2 kb recombinant plasmid, which were equal to the size
      of the pGEX-1LamdaT plasmid and CD gene, respectively. Sequencing results showed
      that the full length and sequence of nucleotide acid of the inserted gene in
      extracted recombinant plasmid was completely identical to the CD gene. In vitro,
      B16-F10 cells treated by supernatant fluid were remarkably damaged
      morphologically, and the cell growth was significantly inhibited. Experiments on
      the mice melanoma model showed that after treatment with a combination of
      transfected Bifidobacterium infantis and 5-FC, the tumor volume was significantly
      inhibited compared with controls. CONCLUSION: The foreign gene, CD gene, was
      correctly inserted into pGEX-1LambdaT plasmid and transferred into
      Bifidobacterium infantis. CD/5-FC suicide gene therapy system mediated by
      Bifidobacterium infantis demonstrated a good antitumor effect on melanoma in
      vitro and in vivo.

PMID- 15842786
TI  - Effects of {2-[(3-carboxy-1-oxoprogy1)amino]-2-deoxy-D-glucose} on human
      hepatocellular carcinoma cell line.
AB  - AIM: To study the effects of {2-[(3-carboxy-1-oxoprogy1)amino]-2-deoxy-D-glucose
      (COPADG) on cultured human hepatocellular carcinoma cells (HepG2). METHODS: HepG2
      cells were cultured in RPMI-1640 medium. Cell proliferation was determined by MTT
      assay. Apoptosis was determined by fluorescence microscopy, transmission electron
      microscopy, agarose gel electrophoresis of DNA fragmentation, and flow cytometry.
      RESULTS: At the concentration ranging between 1-30 micromol/L, COPADG potently
      inhibited the growth and induced apoptosis of HepG2 cells. CONCLUSION: COPADG
      could effectively induce apoptosis in human hepatocellular carcinoma cells. More
      investigations are warranted for the potential use of this compound as a new
      agent for the non-surgical management of human hepatocellular carcinoma.

PMID- 15842789
TI  - Prevalence of specific cardiovascular disease risk factors in young Newfoundland
      and Labrador adults living in urban and rural communities.
AB  - INTRODUCTION: The province of Newfoundland and Labrador has a high rate of
      cardiovascular disease. Risk factors of cardiovascular disease have not been well
      studied in young adults. There are reasons to believe that the prevalence of
      cardiovascular disease risk factors may be higher in young adults residing in
      rural versus urban settings. METHODS: 540 men and women, ages 18 to 34 years and
      residing in urban and rural areas of Newfoundland and Labrador were compared for
      cigarette smoking and for body size. Both body mass index and waist circumference
      measures were used to indicate body size. Education level and family income were
      also studied. Data were collected via personal interview as part of a larger
      study, Nutrition Newfoundland and Labrador. RESULTS: No difference was noted
      between the 2 groups in regular smoking or BMI. More female rural residents had a
      waist circumference above the accepted cut-off compared with female urban
      residents (32.5% v. 17.0%). CONCLUSION: Young adults in urban and rural areas
      both experience high rates of modifiable risk factors for CVD. Some may be more
      prevalent in rural areas. Prevention programs should include young adults,
      especially those residing in rural areas.

PMID- 15842790
TI  - Inappropriate use of antibiotics for acute respiratory tract infections in a
      rural emergency department.
AB  - INTRODUCTION: Evidence-based reviews and guidelines recommend lowering antibiotic
      prescription rates for acute respiratory tract infections (ARIs). OBJECTIVE: To
      determine the number of patients presenting with uncomplicated ARIs at the walk
      in emergency department (ED) of a rural community health centre and to determine
      the antibiotic prescription rate for each type of ARI. METHODS: A one-year
      retrospective data collection of a rural ED was carried out using MEDITECH and
      chart review to determine numbers of patients presenting with an ARI; antibiotic
      prescriptions were recorded according to ARI diagnosis. RESULTS: ARIs accounted
      for 22% of all patients seen by the ED doctor. In 57% of the ARIs diagnosed,
      patients were prescribed an antibiotic. Individual rates ranged from 2% for
      influenza to 100% for pneumonia. A breakdown of rates for each type of ARI is
      provided. CONCLUSIONS: Antibiotic prescription rates for ARIs remain high, with
      some ARIs being more inappropriately managed than others. The rate of patients
      presenting with ARIs to the study ED was higher than in some other EDs, possibly
      reflecting the problems of recruiting and retaining family doctors in many rural
      areas, including ours.

PMID- 15842791
TI  - Understanding the role of nurse practitioners in Canada.
AB  - The practice of medicine and nursing continues to evolve as a result of changes
      in knowledge, technology and health care needs. New areas of specialization have
      developed and, in particular, the roles and duties of registered nurses have been
      expanded. This expansion has enabled nurses with advanced education and skills to
      function as independent and interdependent clinicians who practise in partnership
      with physicians and other health care professionals.

PMID- 15842792
TI  - Use of traditional Mi'kmaq medicine among patients at a First Nations community
      health centre.
AB  - INTRODUCTION: The provision of complete, effective, and culturally sensitive
      health care to First Nations communities requires a familiarity with and respect
      for patients' healing beliefs and practices. PURPOSE: This study addresses one
      aspect of cross-cultural care by attempting to understand the use of Mi'kmaq
      medicine among patients at a community health centre and their attitudes toward
      both Mi'kmaq and Western medicine. METHODS: A questionnaire was completed by 100
      patients (14 men, 86 women) at the clinic. The majority (66%) of respondents had
      used Mi'kmaq medicine, and 92.4% of these respondents had not discussed this with
      their physician. Of those who had used Mi'kmaq medicine, 24.3% use it as first
      line treatment when they are ill, and 31.8% believe that Mi'kmaq medicine is
      better overall than Western. Even among patients who have not used Mi'kmaq
      medicine, 5.9% believe that it is more effective than Western medicine in
      treating illness. CONCLUSION: These results have implications for the delivery of
      health care to First Nations patients, especially in terms of understanding
      patients' health care values and in meeting the need to provide effective cross
      cultural care.

PMID- 15842793
TI  - Diagnosing pulmonary embolism in a rural setting.

PMID- 15842794
TI  - A strategic plan for eliminating rural hospital services through the process of
      regionalization.

PMID- 15842795
TI  - CMA Web site--drug information.

PMID- 15842797
TI  - [Quality control and standardization of immunohistochemistry].

PMID- 15842798
TI  - [Expression of survivin gene in pancreatic carcinoma].
AB  - OBJECTIVE: To determine the expression status of survivin gene in pancreatic
      carcinoma. METHODS: Expression of survivin gene was evaluated by
      immunohistochemistry, Western Blot and RT-PCR in 59 cases of pancreatic carcinoma
      along with their corresponding adjacent benign tissues, 11 cases of chronic
      pancreatitis, and 7 pancreatic carcinoma cell lines. RESULTS: The positive
      expression rate of survivin in pancreatic carcinoma was 72.8% (43/59). There was
      no relationship between the expression of survivin and tumor stage and
      differentiation. No expression of survivin was detected in benign tissue adjacent
      to the tumors as well as in samples of chronic pancreatitis. All 7 pancreatic
      carcinoma cell lines showed a positive expression of survivin mRNA and protein.
      CONCLUSIONS: The expression of survivin appears to be tumor specific to some
      extent in our pancreatic carcinoma samples. Survivin may be an ideal target for
      therapy against pancreatic carcinoma.

PMID- 15842799
TI  - [Study on loss of heterozygosity and microsatellite instability in hepatocellular
      carcinoma].
AB  - OBJECTIVE: To investigate the role of loss of heterozygosity (LOH) in tumor
      suppressor genes (TSG) and microsatellite instability (MSI) in
      hepatocarcinogenesis, as well as their correlation with clinicopathologic
      features. METHODS: LOH in 6 TSG (APC, DCC, MCC, OGG1, p53 and RB1) was detected
      in 36 informative cases of hepatocellular carcinoma (HCC), among 92 surgically
      resected HCC. Thirteen polymorphic microsatellite markers were also studied in 15
      of these cases by microdissection-based PCR amplification and direct DNA
      sequencing. The correlation between genetic alterations and clinicopathologic
      features was analyzed. RESULTS: The overall incidence of LOH in HCC was 41.7%
      (15/36). There was no LOH in MCC gene. 46.2% (6/13) microsatellites showed LOH in
      9 of the 15 cases of HCC (60%). Certain clinicopathologic differences were
      observed between cases (number = 7) with LOH in APC, OGG1 and DCC ("type I") and
      cases (number = 8) with LOH in p53 and RB1 ("type II"). The mean tumor size of
      these two types was 2.9 (+/- 1.7) cm and 7.2 (+/- 3.4) cm, respectively (P <
      0.01); and the mean survival was 72.0 (+/- 38.6) months, and 51.0 (+/- 30.4)
      months, respectively (P < 0.05). CONCLUSIONS: Compared with MSI pathway, LOH
      pathway plays a more important role in the development of HCC. A multistep
      hepatocarcinogenesis is likely, with LOH in APC, OGG1 and DCC ("type I") being an
      early event and LOH in p53 and RB1 ("type II") being a late event. On the other
      hand, MCC gene seems to play no role in the whole process.

PMID- 15842800
TI  - [Expression of hepatocyte growth factor/c-Met system in nasopharyngeal carcinoma
      and its biological significance].
AB  - OBJECTIVE: To investigate the expression of hepatocyte growth factor (HGF), and
      its receptor c-Met protein in nasopharyngeal carcinoma (NPC) and CNE-2 NPC cell
      line, to correlate their expression level with clinicopathologic features and to
      study the effect of HGF/c-Met system on the invasive and metastatic potential of
      NPC. METHODS: Forty-five biopsies were collected from pre-treatment NPC patients
      during the period from 1999 to 2003. Immunohistochemical staining was used to
      detect the expression of HGF-alpha subunit and c-Met protein in NPC tissues. The
      association between expression of these proteins and clinicopathologic features
      was statistically analyzed. The expression of HGF and c-Met, as detected by flow
      cytometry, in CNE-2 NPC cell line (with or without exogenous HGF) was compared.
      Western blot analysis and reverse transcriptase-polymerase chain reaction (RT
      PCR) were also applied to evaluate the protein and mRNA expression of c-Met in
      CNE-2 cells. RESULTS: In the 45 cases studied, the expression rate of c-Met was
      91.1% (41/45). Only 1 case (2.2%, 1/45) showed positive signal for HGF in
      neoplastic cells. Instead, HGF was expressed in surrounding lymphocytes. The
      expression of c-Met positively correlated with lymph node metastasis (P = 0.024).
      There was also a positive correlation between expression of c-Met by tumor cells
      and expression of HGF by surrounding lymphocytes (r(s) = 0.450, P = 0.002).
      Moreover, the expression of c-Met was higher if there was a higher expression of
      HGF by lymphocytes (P = 0.009). However, there was no association between
      expression of c-Met and clinicopathologic features, such as age, gender,
      histopathologic type and clinical stage. After treatment with HGF for 24 hours,
      the percentage of c-Met-positive cells was significantly increased in CNE-2 cell
      line, from (46.6 +/- 9.02)% to (85.8 +/- 6.05)% (P = 0.003). The c-Met protein
      expression and c-Met mRNA level were also enhanced in CNE-2 cells with HGF
      treatment. However, endogenous HGF was not detected in CNE-2 cells, regardless of
      HGF treatment. CONCLUSIONS: HGF may play an important role in the development of
      NPC metastasis by inducing the expression of c-Met in tumor cells via a
      paracrine, instead of an autocrine, pathway.

PMID- 15842801
TI  - [Comparative genomic hybridization: the profile of chromosomal imbalances in
      esophageal squamous cell carcinoma].
AB  - OBJECTIVE: To characterize the profile of chromosomal imbalances of esophageal
      squamous cell carcinoma (SCC) in Linzhou, the high prevalence area of Henan
      province. METHODS: Comparative genomic hybridization (CGH) was used to examine 52
      cases of primary SCC of esophagus. RESULTS: Gains in part or in whole of
      chromosome 3q, 8q, 5p, 1q, 6q, 18p, 20q and losses of 3p, 1p, 9q, 19p, 4p, 8p
      were detected frequently in SCC (> 20%). Gain of 3q, 5p, 1q, 11q13-14 and loss of
      4pq, 13q were all significantly correlated with pathologic staging (P < 0.05).
      Gains of 8q, loss of 4p were linked to nodal metastasis (P < 0.05). Gains of 2p
      and loss of 4pq, 11q14-qter were associated with distant organ metastasis (P <
      0.05). CONCLUSION: These observations suggest that 3q, 8q, 5p, 1q, 6q, 18p, and
      20q may contain SCC-related oncogenes; 3p, 1p, 9q, 19p, 4p and 8p may contain SCC
      related tumor suppressor genes. It is likely that gain of 3q, 5p, 1q, 11q13-14
      and loss of 4pq, 13q are the genetic aberrations critical for the development of
      esophageal carcinoma, whereas gains of 8q, 2p and loss of 4pq, 11q14-qter are
      considered later events associated with tumor progression and are thought to
      confer metastatic potential to esophageal carcinoma. Furthermore, nodal and
      distant organ metastases involve different genes.

PMID- 15842802
TI  - [Clinicopathologic analysis of pulmonary lymphangioleiomyomatosis].
AB  - OBJECTIVE: To investigate the clinicopathological features of pulmonary
      lymphangioleiomyomatosis (PLAM). METHODS: By means of HE and immunohistochemistry
      (SP method) studies, the clinical and pathological features of 5 PLAM cases were
      analyzed and the related literature reviewed. RESULTS: PLAM was a rare lung
      disease of unknown etiology and was restricted to females who were generally pre
      menopausal. Pathological features showed abnormal smooth muscle cells (LAM cells)
      line the airways, lymphatics and blood vesssels leading to airflow obstruction
      and replacement of the lung parenchyma by cysts. LAM cells were positive for
      HMB45. Clinically the disease was categorized by dyspnoea, haemoptysis, recurrent
      pneumothoraces and chylous effusions. CONCLUSIONS: PLAM should be considered when
      recurrent pneumothorax, haemoptysis and dyspnoea occur in females. Pathologic
      examination of lung tissue biopsy is required for confirmation of PLAM diagnosis.

PMID- 15842803
TI  - [In vitro binding of p53 and telomeric repeat factor 2].
AB  - OBJECTIVE: To clarify the regulation of p53 through telomere pathway by
      investigating the molecular interaction between p53 and the main telomere
      associated protein Telomeric Repeat Factor 2 (TRF2) in vitro. METHODS: Four
      different p53-GST (glutathione S-transferase) fusion proteins and GST were
      expressed in E. coli and purified through glutathione sepharose 4B beads. The
      human recombinant p53s included wild type p53 (1-393), N terminus-truncated form
      p53 2C (95-393), C terminus-truncated form p53 N5 (2-293) and single amino acid
      mutant p53 R175H (175 arginine to histidine). Purified p53-GST fusion proteins
      and GST were mixed with cellular protein extracts of human breast cancer cells
      MCF-7 in vitro by pull down. The molecular interaction between p53 and TRF2 were
      detected by Western blot. RESULTS: SDS-PAGE and Coomassie brilliant blue staining
      showed that the molecular weights of all purified proteins were as expected, with
      purities over 90%. Western blot of TRF2 indicated that both wild type p53 and p53
      R175H could bind with TRF2 of MCF-7 cells in similar capacity, while GST alone
      failed to do so. The molecular interaction between p53 2C and TRF2 was enhanced.
      In contrast, the interaction between p53 N5 and TRF2 was significantly reduced.
      CONCLUSIONS: p53 can interact with TRF2 directly and specifically in vitro, with
      C terminus of p53 (293-393) being the binding region for their interaction. This
      C terminus-dependent interaction between p53 and TRF2 may be related to the
      cellular activities induced by telomere alterations.

PMID- 15842804
TI  - [Regulatory effects on apoptotic activities of gastric cancer cell line by over
      expression of Smac gene].
AB  - OBJECTIVE: To investigate the effects of overexpression of second mitochondria
      derived activator of caspases (Smac) gene on apoptosis of gastric cancer cells.
      METHODS: Under the induction of liposome, MKN-45 cells were transfected by Smac
      gene and incubated with G418 for subclone selection. Reverse transcriptase
      polymerase chain reaction and Western blot were used to determine cellular Smac
      gene expression. After induction of apoptosis by mitomycin (MMC), cell
      viabilities were analyzed using trypan blue stain. Apoptosis was measured by
      electronic microscopy, acridine orange-ethidium bromide fluorescent staining and
      in situ terminally labelled transferase technique (TUNEL). Western blot and
      colorimetry were used to assess cellular caspase-3 expression and its activity.
      RESULTS: The Smac mRNA and protein levels in MKN-45/Smac subclone cells (subclone
      consistently expressing Smac gene) were significantly higher than those in MKN-45
      (P < 0.01). When compared with those in MKN-45, cell viabilities of MKN-45/Smac
      were reduced by 10.0% to 30.8% (P < 0.01), after treatment with 10 microg/ml MMC
      for 6 to 24 hours. Some of the MKN-45/Smac cells showed characteristic
      morphologic changes of apoptosis, their apoptotic rate being increased by 21.2%
      (P < 0.01). After treatment with MMC, caspase-3 expression and its activity in
      MKN-45/Smac cells were significantly higher than those in MKN-45 (P < 0.01).
      CONCLUSIONS: Overexpression of Smac in gastric cancer cell line significantly
      improves expression and activity levels of caspase-3 after induction by MMC. Such
      apoptosis-inducing effect establishes a novel strategy for regulating the
      apoptosis activity of gastric cancer.

PMID- 15842805
TI  - [Changes of fibronectin and type IV collagen expression in cultured rat mesangial
      cells transfected with Smad 2 vector].
AB  - OBJECTIVE: To study the changes of fibronectin (FN) and type IV collagen (ColIV)
      expression in cultured rat mesangial cells (MsC) transfected with Smad 2 vector
      and to investigate the molecular mechanism of glomerular extracellular matrix
      accumulation in glomerulosclerosis via transforming growth factor-beta (TGF
      beta)/Smad signal pathway. METHODS: Smad 2 vector was transfected into MsC by
      calcium phosphate. Western blot analysis was used to detect Smad 2 protein. The
      expression of FN and ColIV proteins and their mRNAs was determined by Western
      blot and reverse transcriptase-polymerase chain reaction respectively. RESULTS:
      Four MsC clones (T-12, T-31, T-35, T-40) with Smad 2 overexpression were
      established. The expression of FN and ColIV was significantly increased at mRNA
      and protein levels in two (T-12, T-31). Compared with controls, the expression of
      FN proteins and mRNAs in these two clones was 2.4 times (P < 0.05) and 2.7 times
      (P < 0.05) higher respectively. The expression of ColIV proteins and mRNAs was
      2.9 times (P < 0.01) and 3.3 times (P < 0.01) higher respectively. CONCLUSIONS:
      It is postulated that Smad 2 in TGF-beta/Smad signal pathway is important in
      promoting the accumulation of FN and ColIV in sclerotic glomeruli of diseased
      kidneys.

PMID- 15842806
TI  - [Homocysteine induces macrophage inflammatory protein-1alpha expression by
      activating NF-kappaB in THP-1 monocytes].
AB  - OBJECTIVE: To investigate the effect of homocysteine (HCY) on activation of
      nuclear factor (NF-kappaB) and inhibitory factor IkappaB-alpha in human monocyte
      cell line THP-1, as well as its association with macrophage inflammatory protein
      (MIP-1alpha) upregulation. METHODS: THP-1 monocytes were incubated with HCY, with
      and without NF-kappaB inhibitor pyrolidine dithiocarbamate (PDTC) pretreatment.
      Northern blot analysis and flow cytometry were used to detect MIP-1alpha mRNA and
      protein respectively. The nuclear protein NF-kappaB P65 subunit and the
      inhibitory protein IkappaB-alpha were analyzed by Western blotting. RESULTS:
      Compared with controls, HCY, at a concentration of 0.1 mmol/L, was able to
      enhance the expression of MIP-1alpha mRNA (up to 3.69-fold) and protein (1.16
      fold) in THP-1 monocytes, as well as enhance NF-kappaB P65 transcription to
      nuclear proteins. These actions were significantly suppressed after pretreatment
      with 100 micromol/L PDTC for 30 minutes before HCY incubation; whereas incubation
      of THP-1 monocytes with PDTC only had no effect on both the expression of MIP
      1alpha and nuclear transcription of NF-kappaB P65. Moreover, the level of IkappaB
      alpha protein in THP-1 monocytes decreased after a 30-minute incubation with HCY,
      which gradually increased after 120 minutes. CONCLUSIONS: Homocysteine at a
      pathologic concentration stimulates MIP-1alpha expression in THP-1 monocytes,
      probably via NF-kappaB activation. Such activation may be caused by enhanced
      phosphorylation and degradation of the inhibitor protein IkappaB-alpha.

PMID- 15842807
TI  - [Effects of interaction between vascular endothelial cells and monocytes on
      expression of matrix metalloproteinase-2 and of tissue inhibitor of
      metalloproteinases 2 and regulation of pravastatin].
AB  - OBJECTIVE: To analyze the effects of interaction between vascular endothelial
      cells and monocytes on the expression of matrix metalloproteinase-2 (MMP-2) and
      tissue inhibitor of metalloproteinase 2 (TIMP-2), as well as the regulation of
      pravastatin. METHODS: A co-cultured system of monocytes and endothelial cells was
      established through addition of THP-1 to human umbilical vein endothelial cells
      (HUVECs) in various rates. After 24 hours, the changes in activity and expression
      of MMP-2 and TIMP-2 in the co-culture system were studied by zymography and
      reverse zymography. The 1:1 co-culture system was selected and one control group
      (no pravastatin added) and experimental groups (with concentration of pravastatin
      being 0.1, 0.5 and 1.0 micromol/ml respectively) were studied. All groups were
      cultured for another 24 hours and analyzed in the same way. RESULTS: Compared to
      the single cultured HUVECs, the activity of proMMP-2 in the co-cultured system
      increased by 2.09, 2.46 and 2.07 folds respectively (number = 8, P < 0.01). There
      was also activated MMP-2 secretion in the co-culture system. The secretion of
      proMMP-2 and active MMP-2 in the 1:1 co-cultured system was most obvious. After
      pravastatin treatment, the activity of proMMP-2 and MMP-2, decreased
      significantly (number = 8, P < 0.01). MMP-2 secretion was completely suppressed
      after 1.0 micromol/ml pravastatin treatment. Reverse zymography revealed that,
      compared to the single culture HUVECs or THP-1, the secretion of TIMP-2 decreased
      in the co-cultured system, regardless of the ratio of mixture. However,
      pravastatin had no obvious effect on TIMP-2. CONCLUSIONS: Interaction between
      vascular endothelial cells and monocytes may contribute to the secretion and
      activation of MMP-2 and suppress secretion of TIMP-2. Pravastatin may inhibit the
      secretion and activation of MMP-2.

PMID- 15842808
TI  - [Investigation on the relationship between multidrug resistance and expression of
      glucosylceramide synthase in human breast carcinoma cells].

PMID- 15842809
TI  - [Expression of multidrug resistance-associated gene in non-small cell lung cancer
      and its correlations with telomerase reverse transcriptase and genes related to
      apoptosis].

PMID- 15842810
TI  - [Exploration the methodology of quantitation of microvessel density in the
      tissues of solid carcinoma].

PMID- 15842811
TI  - [The role of beta-amyloid peptide in pathogenesis and immunotherapy of
      Alzheimer's diseases].

PMID- 15842812
TI  - [Isolation and identification of endothelial progenitor cells from peripheral
      blood].

PMID- 15842813
TI  - [Landscaping the terrain of the Sino-Germany Symposium on new development on
      surgical and basic pathology].

PMID- 15842814
TI  - [Encephalic lymphomatoid granulomatosis].

PMID- 15842815
TI  - [Multicentric angisarcoma of the skull].

PMID- 15842816
TI  - [Renal collecting duct carcinoma associated with tumor embolus in the inferior
      vena cava].

PMID- 15842817
TI  - [Glomus tumor of the trachea].

PMID- 15842822
TI  - [Intervention of antioxidant system function of aged rats by giving fruit juices
      with different antioxidant capacities].
AB  - OBJECTIVE: To observe the effects of fruit juices with different antioxidant
      capacity on antioxidant system function of aged rats. METHODS: Thirty Wistar rats
      were randomly divided into three groups: pomegranate juice and apple juice as two
      experimental groups, while distilled water as normal control group. They were
      administrated fruit juices or distilled water respectively by gavage daily for 4
      weeks. At the end of experiment, the antioxidant system function was assessed.
      RESULTS: The aged rats in pomegranate juice group showed significantly higher
      serum antioxidant capacity (0.90 +/- 0.13) mmol/L than that in control group
      (0.79 +/- 0.10) mmol/L (P < 0.05). The concentrations of serum carbonyl and oxLDL
      were decreased significantly in pomegranate juice group as compared to the
      control group (P < 0.05). The percentage of injured blood lymphocyte DNA and the
      ratio of tail length/total length were declined significantly in pomegranate
      juice group (P < 0.05 and P < 0.01 respectively). The apple juice showed no
      effects except decreased ratio of tail length/total length of injured lymphocyte
      DNA. There were no changes in concentrations of serum vitamin C, vitamin E,
      urinary 8-OH-dG excretion and the activities of serum SOD, GSH-Px, CAT among
      three groups. CONCLUSIONS: The pomegranate juice should possess higher
      antioxidant capacity and might improve the antioxidant system function of aged
      rats, while the apple juice is relatively lower in antioxidant capacity and not
      very effective. The polyphenols in pomegranate juice might be the important
      functional components.

PMID- 15842823
TI  - [Polymorphism of alcohol metabolizing-related enzyme genes and its correlation
      with drinking-behaviors in 201 cases of Chinese Han healthy population].
AB  - OBJECTIVE: To study the distribution of genotypes about alcohol dehydrogenase 2
      (ADH2) and aldehyde dehydrogenase 2 (ALDH2) and its relationship with drinking
      behaviors in Chinese Han healthy population as to providing a theoretic direction
      for filtering out high-risk and sensitive individuals and taking preventive
      measures to decrease the alcohol-related diseases. METHODS: Using questionnaires
      to select subjects (201 persons, including men 104, women 97) for collecting
      blood samples and data about drinking-behaviors. Techniques of polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) were used to detect
      the genotypes of ADH2 and ALDH2. RESULTS: Heterozygous ADH2 and homozygous ALDH2
      were the two dominant ones (respectively 53.23%, 68.16%). There were no
      statistical differences among the distributions of nine combinations of ADH2
      genotypes and ALDH2 ones. The difference of distribution of homozygous ALDH2
      between males having high and middle drinking-frequencies seemed to be
      statistically meaningful. CONCLUSION: The proportion of individuals carrying
      about "susceptible genotypes of alcohol-related diseases" in Chinese Han healthy
      population should be more than one half (68.16%), which calls on reinforcing the
      surveillance and preventing the alcohol-related diseases. Correlation between
      genotypes of ADH2 and ALDH2 and alcohol-related diseases should be more
      important.

PMID- 15842824
TI  - [Safety destruction of tetramethylene disulfotetramine and its medical waste].
AB  - OBJECTIVE: To develop suitable methods for safety destruction of tetramethylene
      disulfotetramine (TETS) and the medical wastes polluted by TETS. METHODS: The
      chemical stability of TETS was evaluated under the conditions of acid, alkali and
      high temperature. TETS was treated with sodium hydroxide, hydrochloric acid,
      sulfuric acid and nitric acid under various treatment conditions, i.e.
      concentration, temperature and time, followed by determining remaining TETS using
      gas chromatograms to estimating the degradation efficiency of TETS. TETS was put
      into ampoule and heated under the different conditions of temperature and time.
      After heat treatment, TETS residue was determined. For evaluating the absorption
      factor of active carbon to TETS in water and blood, active carbon was added into
      the water and blood with content of TETS, incubated at room temperature for 24
      hours, and then determined the remaining TETS in water and blood. RESULTS: The
      complete degradation of TETS was achieved by one of the following treatments:
      heating with 6.0 mol/L hydrochloric acid at 100 degrees C for half an hour,
      heating with 3.0 mol/L hydrochloric acid or 6.0 mol/L sodium hydroxide at 100
      degrees C for 3 hours, mixing with concentrated sulfuric acid or nitric acid at
      room temperature for 24 hours, and dry heating at 300 degrees C for 4.5 hours.
      Active carbon showed a marked effectiveness in absorbing the TETS in blood and
      water, with the mean absorption efficiency of over 90%. CONCLUSIONS: The results
      of this study suggest that TETS powder should be degraded by acid or alkali, and
      that the solid medical wastes polluted by TETS should be destroyed at high
      temperature. For the blood and water having contents of TETS, the active carbon
      should be used as to absorbing the TETS and then be destroyed at high
      temperature.

PMID- 15842825
TI  - [Toxicokinetics of tetramethylene disulphotetramine].
AB  - OBJECTIVE: To explore toxicokinetics of tetramethylene disulphotetramine (TETS)
      in rabbit and the effects on toxicokinetics of TETS after activated charcoal by
      gavage. METHODS: Eight rabbits were exposed through gavage and vein respectively,
      the blood samples were collected from the center artery in ear of rabbit at an
      arranged time. Four rabbits were exposed after being intubated into urethra and
      common bile duct. The samples of bile and urine were collected at arranged times.
      After being exposed by gavage, activated charcoal (1 g/kg) was administrated in
      the activated charcoal group and the distilled water (1 g/kg) administrated to
      the controls. The samples of blood were collected from the center artery in ear
      of rabbit at arranged times. The contents of TETS in samples were determined by
      GC/NPD method. Analysed by the 3p87 soft, toxicokinetics parameters of TETS were
      acquired. RESULTS: TETS was eliminated very slowly in rabbit. The plasma half
      time in elimination phase (Tke1/2) of TETS was 56.9 hours in vein exposure group
      and 262.5 hours in oral exposure group respectively. The plasma clearance (CL) of
      it was only 15.4 ml.kg(-1).h(-1) in oral exposure group and 24.1 ml.kg(-1).h(-1)
      in vein exposure group. TETS was eliminated from urine in rabbit. The eliminated
      amount of it from urine was more 5 times than from bile. All parameters of
      toxicokinetics of TETS were significantly different between the activated
      charcoal group and the control. Compared to the control, Tke1/2 of TETS in the
      activated charcoal group was equal to 55%, CL was increased over 3-fold, area
      under the curve was equal to 30%. CONCLUSION: TETS was a poison eliminated very
      slowly in body. The eliminated amount of it from urine was more than from bile.
      The excretion of TETS could be quickened after activated charcoal by gavage.

PMID- 15842827
TI  - [Evaluation of therapeutic project on acute tetramethylene disulphotetramine
      poisoning and effect on intelligence in children].
AB  - OBJECTIVE: To evaluate four therapeutic measures on acute tetramethylene
      disulphotetramine (TETS) poisoning and the effects of it on intelligence of
      children. METHODS: All 86 patients of acute TETS poisoning were randomly divided
      into 4 groups (the control group, sodium valproate group, sodium
      dimercaptopropane sulfonate group and the hemoperfusion group). The therapeutic
      effects were observed after the arranged treatment was administrated. According
      to age, residence, sex, education and domestic economy, 30 children were matched
      by 1:1 with children of TETS poisoning. RESULTS: The termination time of seizure,
      doses of diazepam, mental symptoms and the continual time of mental symptoms were
      not significantly different among these three groups. After hemoperfusion, the
      seizure of patients was terminated or the frequency was obviously decreased, but
      the level of TETS in blood was not reduced. The average scores of full
      intelligence quotient (FIQ), the verbal intelligence quotient (VIQ) and the
      performance intelligence quotient (PIQ) of children in poisoning group were 9.1,
      8.8 and 7.7 less than the controls. The average scores of FIQ of children with
      bad state were 15 less than the controls. CONCLUSION: Therapeutic effects of
      sodium valproate and sodium dimercaptopropane sulfonate on acute TETS poisoning
      should be not better than using diazepam and sodium phenobarbital. Therapeutic
      effects of hemoperfusion on TETS poisoning is good. TETS poisoning should have a
      great influence on intelligence of children.

PMID- 15842828
TI  - [Gene expression profiles in early stage of BALB/c 3T3 cells' transformation
      promoted with 12-O-tetradecanoylphorbol-13-acetate].
AB  - OBJECTIVE: To elucidate the potential molecular mechanism responsible for the
      early time of tumor promotion, gene expression profile was studied in the
      transformed BALB/c 3T3 cells induced by 12-O-tetradecanoylphorbol-13-acetate
      (TPA). METHODS: The two-stage cell transformation model was established by using
      the initiator of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and promoter of TPA.
      Cell proliferation was measured by trypan blue staining and cell cycle analysis
      was carried out by flow cytometry assay. A cDNA microarray representing 1 152
      genes was used to investigate the gene expression profiles of BALB/c 3T3 cells
      exposed to TPA at 4 h and 24 h respectively. RESULTS: TPA could effectively
      inhibit cell proliferation and induce the G1 and S cell cycle arrested in the
      early time. Moreover 19 genes were found differentially expressed at least
      twofold in the TPA treated cells as compared with the control cells, 9 of them
      were upregulated and 10 downregulated. Most of the differentially expressed genes
      were involved in cell proliferation, differentiation or apoptosis, and related to
      ras or p53 signal transduction pathway. CONCLUSION: TPA could influence the
      transcriptional expression of some genes related to cell cycle modulation and
      ultimately result in the cell growth arrest.

PMID- 15842829
TI  - [Detection of interaction of binding affinity of aromatic hydrocarbon receptor to
      the specific DNA by exonuclease protection polymerase chain reaction assay].
AB  - OBJECTIVE: To establish an exonuclease protection mediated polymerase chain
      reaction (PCR) assay for the non-radioactive, sensitive detection of the binding
      of protein and DNA. METHODS: The 1 pmol/L-10 nmol/L 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) dissolved in dimethyl sulphoxide (DMSO), was added into 100 microl
      SD rat hepatic cytosol in vitro, which contained different amount of aromatic
      hydrocarbon receptors (AhR) and relative proteins, and ligand-AhR-DRE complex
      were formed in addition to 1 fmol/L-100 nmol/L DNAs probes containing the
      sequence of DRE. With the digestion of Exonuclease III and S1 nuclease, free DNAs
      were digested to oligonucleotide and binding DNA remained due to protein (AhR)
      protection and be amplified by PCR. The results of PCRs were shown by loading on
      2% agarose electrophoresis. DMSO was used as negative control and blank control
      was set up. RESULTS: Target DNA (285 bp) could be observed in the ligand groups,
      but not in the control group. The minimal amount of receptor was 2.5 fmol/L and
      the minimal amount of DNA probes was 2 fmol. CONCLUSIONS: Exonuclease protection
      mediated PCR assay should be a good non-radioactive tool to quantify the
      interaction of protein and DNA with high sensitivity and simplicity.

PMID- 15842832
TI  - [Effects of diethylhexyl phthalate on lipid peroxidation and the life-span in
      Drosophila melanogaster].
AB  - OBJECTIVE: To observe the effects of diethlhexyl phthalate (DEHP) on lipid
      peroxidation and the life span in Drosophila melanogaster. METHODS: Fed
      Drosophila with the concentration 0.20% DEHP of exposure after 0, 14, 28 days,
      the activity of total superoxide dismutase (SOD), CuZn-SOD and the concentration
      of malondialdehyde were determined. At the same time, the longevity test was
      carried out to examine the effect of DEHP on the Drosophila's lifespan. RESULTS:
      The lifespan of Drosophila was shortened in a dose of DEHP exposed groups. The
      indexes of mean life span (MLS), 50% lethal time and mean maximum life span in
      three DEHP-treated groups (concentration of 0.05%, 0.10% and 0.20%) were lower
      than those of the controlled group respectively (P < 0.01 or P < 0.05). The MLS
      of both Drosophila sexes were reduced from the control of 64 days and 59 days to
      the test 60 days-52 days and 54 days-49 days respectively. DEHP decreased the
      activity of SOD (P < 0.01 or P < 0.05), and lead to a time-dependent relation and
      an increase in the concentration of malondialdehyde (P < 0.01 or P < 0.05) in the
      DEHP-exposed Drosophila groups. CONCLUSION: DEHP might promote the process of
      lipid peroxidation and shorten the life span in Drosophila melanogaster. It
      should be one of the reasons in the senescence of Drosophila.

PMID- 15842830
TI  - [Differential expression of osteopontin and bax, bcl-2 by fluoride].
AB  - OBJECTIVE: To study the differential expression of bax, bcl-2 and osteopontin by
      fluoride in the renal tubular cells in vitro. METHODS: The renal tubular cells
      were cultured and exposed to sodium fluoride (NaF) in 1, 5, 7.5, 12.5 mg F-/L
      level. The transcription level of bax, bcl-2 and osteopontin were investigated by
      reverse transcription - polymerase chain reaction (RT-PCR). RESULTS: The
      expression of bax mRNA in 7.5 and 12.5 mgF-/L groups (optical absorption ratio
      value was 2.37 +/- 0.18 and 2.64 +/- 0.19 respectively) was significantly
      increased (P < 0.01). On the contrary, the level of bcl-2 obviously decreased (5
      mg F-/L group optical absorption ratio value, 0.80 +/- 0.22, P < 0.05; 7.5 mg F
      /L group optical absorption ratio value 0.71 +/- 0.22, P < 0.01). The expression
      mRNA of osteopontin was significantly increased when cells were exposed to
      fluoride at 7.5 mg F-/L (optical absorption ratio value 2.01 +/- 0.40 P < 0.01),
      in that group the tubular cell apoptotic trend was obvious. CONCLUSION: NaF might
      induce tubular cell apoptosis via activation of bax expression and bcl-2
      suppression. Osteopontin might protect the tubule against apoptosis in a lower
      fluoride level, but the function should be decreased in higher fluoride level.

PMID- 15842833
TI  - [The effect on apoptosis in anterior pituitary induced by cadmium chloride and
      its relations with caspase-9 pathway].
AB  - OBJECTIVE: To study the effects of cadmium chloride in anterior pituitary and the
      relation between apoptosis and expression of procaspase-9 mRNA. METHODS: In vivo
      studies:40 SD male rats were randomly distributed into four groups which were
      administered with CdCl2 at different doses by gavage for 6 weeks; IN VITRO
      STUDIES: the rats' anterior pituitary cells were primarily cultured for 120
      hours, then treated with CdCl2 at the dose of 0, 1.56, 3.12, 6.25, 12.50, 25.00,
      50.00, 100.00 micromol/L for 6 hours; The indices included: expression of
      procaspase-9 mRNA, detection of apoptosis with TUNEL assay. RESULTS: The results
      showed the excretion of ACTH, LH seemed to be decreased dramatically and the
      apoptosis inclined to enhance remarkably, and further more, the expression of
      procaspase-9 mRNA appeared to be increased significantly as compared with those
      of the control. It was show that a dose-effect relationship between the CdCl2
      dosing and indices above with the regression analysis and a linear correlation
      between the mean gray value of apoptosis cell and the relative gray value of
      procaspase-9 mRNA positive cell. The results indicated that damnification, for
      example, apoptosis could be caused by certain dose of CdCl2 in anterior pituitary
      cells with dose dependent manner. Caspase-9 might play a role in the occurrence
      of apoptosis. CONCLUSION: It was suggested that cadmium could induce apoptosis of
      anterior pituitary both in vivo and in vitro in the manner of dose-dependent, and
      caspase-9 might play a role during above processes.

PMID- 15842834
TI  - [The study on mechanism of appetite regulation in diet-induced obesity resistant
      rats].
AB  - OBJECTIVE: To explore the cause of decreasing intake food of diet-induced obesity
      resistant (DIO-R) rats. METHODS: Fifty male Sprague-dawley (SD) rats were
      randomly divided into control group and high-fat group and they were fed with
      basic diet and high-fat diet respectively for 13 weeks. DIO-R and diet-induced
      obesity (DIO) rats were selected according to their body weight and the quantity
      of energy intake, then observing the changes of the total food intake, the level
      of serum leptin and plasma NPY were determined by radioimmunoassay and the
      contents of the melanocortin receptor-4 (MCR-4) in brain were determined by
      Western Blot. RESULTS: The total food intake of DIO-R rats was (1 679.1 +/-
      146.8) g. The total food intake of DIO rats was (1 818.4 +/- 148.9) g. The total
      food intake of DIO-R rats was lower than that of DIO rats (P < 0.05). The level
      of plasma NPY of DIO-R rats was (795.24 +/- 83.59) ng/L. The level of plasma NPY
      of DIO rats was (1 007.14 +/- 172.83) ng/L. The level of plasma NPY of DIO-R rats
      was lower than that of the DIO rats (P < 0.05). The levels of serum leptin of
      basic, DIO-R and DIO rats was (4.80 +/- 0.75) microg/L, (9.17 +/- 1.19) microg/L
      and (9.32 +/- 1.04) microg/L. The level of serum leptin of rats in high-fat diet
      group was increased as compared with the rats in basic diet group, but there was
      no significant difference between DIO-R and DIO rats (P > 0.05). The levels of
      brain MCR-4 of basic, DIO-R and DIO rats were (342 +/- 31) mm2, (455 +/- 33) mm2,
      (355 +/- 30) mm2. High fat diets increased the content of brain MCR-4 in DIO-R
      rats. CONCLUSION: DIO-R rats decreased appetite by increasing expression of ob
      gene to reduce activity of NPY pathway and activate the MCR-4 pathway, and thus
      inhibit the increase body of weight.

PMID- 15842835
TI  - [Effects of acrylonitrile in drinking water on monoamine neurotransmitters and
      its metabolites in male rat brains].
AB  - OBJECTIVES: To elucidate the possible involvement of monoamine neurotransmitters
      in the development of neurobehavioral damage produced by acrylonitrile in
      drinking water in male rat brains. METHODS: Totally 30 male SD rats were randomly
      divided into three groups, the control group (n = 10), low dosage group (n = 10),
      and high dosage group (n = 10), which were respectively administered 0 mg/L, 50
      mg/L, 200 mg/L acrylonitrile (AN) in drinking water. The treatment was lasted for
      12 weeks. Seven animals were randomly selected from each group for determination
      of monoamine neurotransmitters in striatum and cerebellum by high performance
      liquid chromatography with electrochemical detector and activities of monoamine
      oxidase in cortex. RESULTS: The contents of dopamine in the striatum of low and
      high dosage groups were decreased to (2.2 +/- 0.7) and (3.2 +/- 2.0) microg/g wet
      tissue, respectively, and compared with that of control group (9.0 +/- 4.2)
      microg/g wet tissue, the differences were statistically significant. There were
      no statistical differences among the contents of dopamine in the cerebellum of
      all rats, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), the major
      metabolite of dopamine in the cerebellum were (186 +/- 41), (245 +/- 90) and (115
      +/- 65) ng/g wet tissue in the control, low and high dosage groups, respectively
      and in low-dosage group they were significantly higher than those in other
      groups. There was dosage-dependently decreasing of the contents of serotonin of
      striatum in the control (249 +/- 34) ng/g wet tissue, low dosage (155 +/- 95)
      ng/g wet tissue and high dosage groups (128 +/- 101) ng/g wet tissue. CONCLUSION:
      This study underlines the importance of alterations in the monoamine
      neurotransmitters system as a possible causative mechanism behind the behavioural
      and functional changes produced by acrylonitrile.

PMID- 15842837
TI  - [Effects of phytoestrogens on gap junctional intercellular communication].
AB  - OBJECTIVE: To observe effects of phytoestrogens quercetin (QC), Genistein (GEN),
      coumestrol (COM), and enterolactone (ENL) on gap junctional intercellular
      communication (GJIC) in HaCaT cells. METHODS: HaCaT cells were exposed to QC,
      GEN, COM, and ENL at 0.1, 1.0, 10.0 and 100.0 micromol/L for 24 hours. The
      effects of phytoestrogens on GJIC were determined by fluorescence redistribution
      after photobleaching (FRAP) technique of using a laser scanning confocal
      microscope (LSCM). RESULTS: QC did not affect the GJIC at 0.1-10.0 micromol/L,
      whereas, GEN, COM, and ENL exhibited inhibition on the GJIC in some extent at 0.1
      10.0 micromol/L without showing significant cytotoxicity. The ratio of
      fluorescence recovery were between 31.77% to 37.06%, which were significantly
      decreased compared the vehicle control (44.74%). CONCLUSION: The phytoestrogens
      GEN, COM, and ENL, but not QC, could inhibit the GJIC function in HaCaT cells at
      concentrations could be reached in human serum in some instance, indicating they
      could, under certain conditions, be cancer promoters. Therefore, it should be
      prudent to use these chemicals as pharmaceuticals or dietary supplements.

PMID- 15842851
TI  - [How to improve the diagnostic and therapeutic levels of oral premalignant
      lesions].

PMID- 15842838
TI  - [Detection of severe acute respiratory syndrome probable patients' virus RNA in
      Hangzhou by using a two loci and a modified nested real-time reverse
      transcription polymerase chain reaction].
AB  - OBJECTIVE: To detect the RNA of severe acute respiratory syndrome virus (SARS
      CoV) by using reverse transcription polymerase chain reaction (RT-PCR) targeted
      for a two loci and a modified nested real-time RT-PCR as to improving the
      reliability and sensitivity of tests. METHODS: A nested RT-PCR was used for
      detecting one fragment of SARS-CoV RNA in oropharyngeal swabs from 3 SARS
      probable patients, 4 SARS suspect patients and other 27 patients with fever in
      Hangzhou, and the nested RT-PCR product from one SARS probable patient was
      sequenced. Meanwhile in these 3 SARS probable patients, other three RT-PCR
      methods, including a hemi-nested RT-PCR targeted for another fragment of SARS-CoV
      RNA, a real-time RT-PCR and a modified nested real-time RT-PCR, were employed to
      detect SARS-CoV RNA. RESULTS: Two positives were found in the 3 SARS probable
      patients, and none positive in 4 SARS suspect patients and other 27 patients with
      fever, using the nested RT-PCR. The sequence of the nested RT-PCR product from
      one SARS probable patient was identified with the counterpart of SARS-CoV genomes
      published in public database. The results of the hemi-nested RT-PCR, the real
      time RT-PCR and the modified nested real-time RT-PCR in the 3 SARS patients were
      consistent with the one of the nested RT-PCR. During detecting specimen with low
      copies of RNA, a weak positive signal was produced after about 35 cycles in the
      real-time RT-PCR, but a strong positive signal was found only after 10 cycles in
      the modified nested real-time RT-PCR. CONCLUSION: It might improve the
      reliability of test by employing RT-PCR targeted for two or more fragments in
      SARS-CoV genome. The modified nested real-time RT-PCR might have higher
      sensitivity than the routine real-time RT-PCR.

PMID- 15842852
TI  - [Standard for evaluation of effect for oral lichen planus (erosive, atrophic)
      (trial implementation)].

PMID- 15842853
TI  - [The p16 methylation in oral leukoplakia and oral squamous cell carcinoma].
AB  - OBJECTIVE: To investigate p16 gene methylation in normal mucosa, leukoplakia with
      hyperplasia and dysplasia and oral squamous cell carcinoma. METHODS: 20 patients
      of leukoplakia with hyperplasia, 11 patients of leukoplakia with mild dysplasia,
      10 patients of leukoplakia with moderate dysplasia, 9 patients of leukoplakia
      with severe dysplasia, 10 patients with OSCC in low grade, 12 patients with OSCC
      in moderate grade, 8 patients with OSCC in high grade, and 10 normal individuals
      were studied on p16 methylation. RESULTS: Rates of p16 methylation were 0 for
      normal individuals, 5% for patients of leukoplakia with hyperplasia, 18% for
      patients of leukoplakia with mild dysplasia, 10% for patients of leukoplakia with
      moderate dysplasia, 22% for patients of leukoplakia with moderate dysplasia, and
      50% for patients with OSCC in low grade, 42% for patients with OSCC in moderate
      grade, and 63% for patients with OSCC in high grade. Rates of p16 methylation
      increased with tissue malignance increase and correlated positively to the tissue
      malignance. The rate (82%) of p16 methylation in OSCC patients with lymph node
      metastasis was significantly high than that (32%) of OSCC patients without lymph
      nodes metastasis. The methylated rates of p16 correlated positively to the
      lacking rates of p16 protein. CONCLUSIONS: It was first reported that p16
      methylation occurred in every stage of leukoplakia cancerization and OSCC
      progression. p16 can be one of the important molecular biological markers for
      leukoplakia cancerization and OSCC progression. p16 methylation is recommended as
      an important marker for diagnosis of OSCC.

PMID- 15842854
TI  - [Effects of glucocorticoids on T helper cells balance in oral lichen planus].
AB  - OBJECTIVE: To investigate the effects of dexamethasone on Th1/Th2 cytokines in
      oral lichen planus. METHODS: Peripheral blood mononuclear cells (PBMC) were
      isolated by density gradient centrifugation from OLP patients and healthy
      controls. PBMC from patients with OLP were stimulated with phytohemagglutinin
      (PHA) and dexamethasone respectively for 72 h. The concentrations of interferon
      gamma (IFN-gamma) and interleukin-4 (IL-4) in culture supernatants were
      determined by ELISA. The mRNA levels for IFN-gamma and IL-4 in culture cells were
      evaluated using semi-quantitative reverse transcription-polymerase chain
      reaction. RESULTS: Compared with healthy controls, the levels of IFN-gamma in OLP
      patients were significantly lower (P < 0.05). The levels of IL-4 were higher, but
      not statistically significant (P > 0.05). The ratios of IFN-gamma/IL-4 were lower
      in patients with OLP (P < 0.05). Dexamethasone significantly inhibited the levels
      of IFN-gamma and IL-4 (P < 0.01). Moreover, IFN-gamma was inhibited significantly
      more than IL-4. The levels of IFN-gamma and IL-4 mRNA expression in culture cells
      were consistent with protein production in supernatants. CONCLUSIONS: Th2 immune
      response is predominant in OLP. Dexamethasone is an immunosuppressant inhibiting
      Th1/Th2 cytokines.

PMID- 15842855
TI  - [Amplification of EMS1 gene in oral carcinogenesis].
AB  - OBJECTIVE: To investigate the amplification of EMS1 gene in the carcinogenesis of
      oral mucosa. METHODS: A total of 78 subjects, including 30 patients with oral
      leukoplakia (OLK), 33 with oral squamous cell carcinoma (OSCC), and 15 healthy
      controls, were studied. By using microdissection method, we obtained normal
      mucosa, hyperplastic epithelia, mild-dysplastic epithelia, moderate-dysplastic
      epithelia, severe-dysplastic epithelia and primary OSCC tissue. Then we analyzed
      EMS1 amplification by using differential PCR. RESULTS: EMS1 amplification began
      from moderate-dysplastic epithelia and occurred in 20.0% OLK cases and 57.6% OSCC
      cases. In the progress of OSCC, no gene amplification was observed in normal
      tissues, non-dysplastic OLK and mild-dysplastic OLK, while in the cases with
      metastasis, amplification frequency increased significantly (P = 0.015).
      CONCLUSIONS: EMS1 amplification parallels with the progress of oral
      carcinogenesis, indicating their potential roles in oral carcinogenesis.

PMID- 15842856
TI  - [Discussion on evaluation of oral lichen planus' therapeutic effects].

PMID- 15842857
TI  - [Treatment strategies for pemphigus].

PMID- 15842863
TI  - [Modulation of Chinese regimen granules of Shenyang on peripheral blood
      lymphocyte subsets of SD rats with SCC of tongue].
AB  - OBJECTIVE: Prospective research demonstrated that Chinese regimen granules of
      Shenyang could prolong survival time and improve survival rate of patients with
      oral squamous cell carcinoma (SCC). But the mechanism was not clear. The purpose
      of this study was to investigate Shenyang's effect on peripheral blood lymphocyte
      subsets of SD rats with SCC of tongue and explore immunological mechanism.
      METHODS: Among 80 SD rats fed by 0.002% 4-nitroquinoline-1-oxide (4NQO) drinking
      water for 36 weeks, 61 rats with SCC of tongue had been found and were randomly
      divided into 4 groups, namely Shenyang A, Shenyang B, positive and blank control
      groups. Before and after high and normal dosage of Shenyang, acanthopanax
      senticoside and water had been given for 15 days respectively, peripheral blood
      lymphocyte subsets were detected with flow cytometry. The data were statistically
      analyzed with paired t Test. RESULTS: Percentage of CD3+ CD4+ T cell and CD3
      CD161a+ NK cell, ratio of CD4+/CD8+ were increased. Percentage of CD3+CD8+ T cell
      was decreased, and the effect was better than that of acanthopanax senticoside in
      improving the percentage of CD3-CD161a+ NK cell. CONCLUSION: Among anti-tumor
      mechanisms of Shenyang it is that corrects disorder of lymphocyte subsets and
      increases percentage of CD3-CD161a+ NK cell.

PMID- 15842865
TI  - [Radiotherapy for immediate reconstruction of mandibular defects with the
      titanium plate after tumor resection of mandible].
AB  - OBJECTIVE: To study the influence of radiotherapy on immediate reconstruction
      with the titanium plate after resection of mandible in oral cancer patients.
      METHODS: Fifty-eight cases (radiation group, 30 patients and control group, 28
      patients) with titanium plate for immediate reconstruction of mandibular defects
      were observed from January, 1997 to May, 2002. The patients of radiation group
      underwent radiotherapy with total doses of 4,050 - 6,540 cGy (mean 5,495 cGy).
      The titanium plate was in radiation fields and was irradiated during the
      radiation therapy. RESULTS: Local infection and fistula accounted for 6 cases and
      plate exposure accounted for 5 in radiation group. Local infection and plate
      exposure happened in 4 and 3 patients in control group respectively. Titanium
      plates were taken in six cases in radiation group and 4 cases in control group by
      re-surgery 4 - 15 months after primary surgery because of local infection. The
      success rates of immediate reconstruction with the titanium plate were 80.0%
      (24/30) in radiation group and 85.7% (24/28) in control group (P > 0.05).
      CONCLUSIONS: The cases of immediate reconstruction with the titanium plate after
      resection of mandible in oral cancer patients can accept postoperative
      radiotherapy.

PMID- 15842867
TI  - [Interaction of vascular endothelial growth factor-C over-expression with tongue
      squamous cell carcinoma cell line Tca8113 with peri-carcinoma lymphatics].
AB  - OBJECTIVE: To detect the role of Vascular endothelial growth factor C (VEGF-C) in
      the interaction of tongue squamous cell carcinoma (TSCC) with the peri-carcinoma
      lymphatics. METHODS: TSCC cells were implanted on the chorioallantoic membrane
      (CAM), in which, group A was transfected by plasmid pREP7 including VEGF-C, group
      B was transfected by plasmid pREP7, and group C was Tca8113. Lymphatic vessels
      were stained by 5'-Nase. Morphologic analysis was used to evaluate the alteration
      of lymphatic vessels density (LVD), area and perimeter. RESULTS: The transplanted
      tumor well on CAM. The expression of VEGF-C in group A was higher than that in
      control group B and C. The LVD, perimeter and area in group A were (5.3 +/-
      0.41)/high-power field, (148 +/- 21) microm and (76.8 +/- 13.5) microm(2)
      respectively in group A, which were significantly higher than that of group B and
      C (P < 0.01), while there were no significant difference between group B and C.
      CONCLUSIONS: CAM is ideal model for the research of lymphatic vessels; Over
      expression of VEGF-C could induce the dilatation and LVD increase of peri-tumor
      lymphatic vessels, which maybe one of the mechanisms that VEGF-C metastasis of
      TSCC through lymphatic vessels.

PMID- 15842868
TI  - [Senile chronic submandibular sialadenitis].
AB  - OBJECTIVE: To evaluate the clinic characteristic and treatment of senile chronic
      submandibular sialadenitis. METHODS: The clinical records of the patients over 50
      years old whose final diagnosis was chronic submandibular sialadenitis were
      reviewed. The patients were diagnosed as neoplasm of submandibular gland before
      operation, There was no radiographic sign of sialolithiasis, no clinical and
      laboratory signs of Sjogren syndrome or related autoimmune disease. RESULTS:
      Thirty-five patients were presented in masses in the submandibular space, which
      was not related to eating. Histopathologic study showed destruction of acinus,
      infiltration of inflammatory cell, and micro-calcification in the intercalated
      duct. CONCLUSIONS: The diagnosis of senile chronic submandibular sialadenitis
      should be considered if a mass in the submandibular space occurs in the old
      patients and radiographic study shows no sialolithiasis and neoplasm. Resection
      of the submandibular gland is not necessary for these patients.

PMID- 15842869
TI  - [The value of endoscopy for the diagnosis and treatment of obstructive salivary
      gland diseases].
AB  - OBJECTIVE: To evaluate the value of sialoendoscopy in the diagnosis and treatment
      of chronic obstructive sialadenitis (COS). METHODS: 25 patients (34 sides) who
      complained of recurrent swelling in the salivary gland region were selected for
      study from Jan. 2003 to Jun. 2003 at the Department of salivary gland diseases,
      School of Stomatology, Wuhan University, including 19 parotid cases (27 sides)
      and 6 submandibular gland cases (7 sides); 16 females and 9 males. And their age
      range was 17 - 77 years, with an average of 43.72 years. Before sialoendoscopy,
      22 parotid cases underwent sialography, and 3 submandibular gland sialoliths
      cases received an additional standard mandibular occlusal film examination.
      RESULTS: Conventional radiographs revealed that 3 cases had submandibular gland
      radiopaque stones, and 22 had COS. Dilatation of main duct of parotid and
      submandibular gland were also found in the radiographs. Sialoendoscopy showed:
      proliferative fibrous materials in the duct; stenosis or dilatation of duct;
      vasodilatation, erythema on the wall of the duct; mucoid plugs and pyogenic
      plugs; irregular lumen shape; radiopaque and radiolucent stones. CONCLUSIONS:
      Sialoendoscopy may be a safe, effective, and minimal invasive method in the
      diagnosis and treatment of COS.

PMID- 15842870
TI  - [A revised scheme for LeFort classification of upper jaw fractures].
AB  - OBJECTIVE: To put forward a revised scheme on LeFort classification for the upper
      jaw fractures. METHODS: 193 consecutive cases with the primary diagnoses of upper
      jaw fractures were involved in this study, for each one of which water's and CT
      scan were available to decide the fracture site and pattern. Data were filed in
      term of classification items as LeFort I, II and III fracture, as well as
      sagittal fracture and alveolar fracture. Statistical analysis was done to
      validate the meliorating thought on and revised scheme on LeFort classification.
      RESULTS: It was validated that of 185 cases with upper jaw fractures only 30.81%
      which presented single-line fracture and 34.06% which presented multiple-line
      fracture were covered with LeFort classification. Additional 13.51% with single
      line fracture and 21.61% with multiple-line fracture could be included when
      LeFort classification was extended with increase of items of sagittal fracture
      and alveolar fracture. Further results revealed that among total 344 sites or
      fracture lines included in 193 cases, 81.10% could be diagnosed fracture pattern
      of LeFort classification. Of 65 fracture sites presenting LeFort III type, 92.31%
      were concomitant with LeFort II type or LeFort I and II type, very few being
      alone. CONCLUSIONS: A revised classification was proposeded that upper jaw
      fractures could be classified into four types as follows: (1) high horizontal
      fracture (corresponding to LeFort II and III type), (2) low horizontal fracture
      (corresponding to LeFort I type), (3) sagittal fracture (including midline and
      para-midline fracture) and (4) alveolar fracture.

PMID- 15842871
TI  - [An adjustable appliance in treatment of obstructive sleep apnea-hypopnea
      syndrome].
AB  - OBJECTIVE: The research tended to approach applying of adjustable appliance in
      the treatment of obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: 30
      OSAHS patients (24 males and 6 females) participated in the adjustable group,
      with a mean age of (49.9 +/- 9.9) years old. AHI was (33.1 +/- 22.7) per hour.
      The control group consisted of 30 OSAHS patients wearing ordinary mandibular
      advancing appliance in the corresponding period, with age, weight and AHI at the
      same level. Monoblind way was designed to obtain and analyze the therapy
      differences. Differences in changes of upper airway, mandible and hyoid bone were
      also analyzed among the doctor-experience position, final adjusted position and
      original position. RESULTS: AHI decreased by 85.5% in the adjustable appliance
      group. The change in AHI was greater significantly (P = 0.025) in the adjustable
      group than in the control group. In the final adjusted position, the amount of
      mandibular advancement was (5.8 +/- 1.4) mm [(71 +/- 26)% of the maximum range of
      protrusion] and that of bite opening (the distance between upper and lower
      incisor edges) was (4.6 +/- 1.1) mm. CONCLUSIONS: The adjustable appliance had
      shown better therapy effect in OSAHS patients. The final adjusted position
      provided useful information on determining mandibular position using other
      appliances.

PMID- 15842872
TI  - [Development of a questionnaire to evaluate the cooperation of adolescent
      orthodontic patients].
AB  - OBJECTIVE: To develop a questionnaire to evaluate the cooperation of adolescent
      orthodontic patients. METHODS: 182 orthodontic patients (9 - 15 years old, 78
      boys and 104 girls) with fixed appliance were selected in Dalian. A questionnaire
      was developed according to the past research and 4 hypotheses. RESULTS: The scale
      is made up of 25 items and 4 factors. The reliability of this scale was confirmed
      (the reliability coefficient > 0.9 and Cronbach alpha coefficient > 0.7).
      CONCLUSION: The questionnaire may be used to evaluate the cooperation of
      orthodontic patients.

PMID- 15842873
TI  - [A clinical study of presurgical nasoalveolar molding in infants with complete
      cleft lip and palate].
AB  - OBJECTIVE: To observe the clinical effect of presurgical nasoalveolar molding in
      infants with complete cleft lip and palate. METHODS: Presurgical nasoalveolar
      molding was performed in 38 infants with cleft lip and palate (26 patients with
      unilateral cleft lip and palate, 12 patients with bilateral cleft lip and
      palate), aged between 5 and 30 days. The width of alveolar cleft was measured
      before and after the operation and the effect of treatment was assessed. RESULTS:
      After 108 - 152 days of therapy, the average width of alveolar cleft decreased by
      5.3 mm in 26 patients with unilateral cleft lip and palate. Nasal profile was
      improved in 76 percent of cases. In 12 patients with bilateral cleft lip and
      palate, the average width of left cleft decreased by 4.7 mm and that of the right
      decreased by 4.2 mm. The distance between right and left cleft increased by 5.1
      mm. Nasal profile was improved in 66 percent of cases. CONCLUSION: Presurgical
      nasoalveolar molding in complete cleft lip and palate can improve nasal profile
      and decrease the width of alveolar cleft.

PMID- 15842874
TI  - [Microstructure and mechanical property of a new IPS-Empress 2 dental glass
      ceramic].
AB  - OBJECTIVE: To investigate the microstructure and mechanical properties of a new
      IPS-Empress 2 dental glass-ceramic. METHODS: AFM, SEM and XRD were used to
      analyze the microstructure and crystal phase of IPS-Empress 2 glass-ceramic. The
      flexural strength and fracture toughness were tested using 3-point bending method
      and indentation method respectively. RESULTS: IPS-Empress 2 glass-ceramic mainly
      consisted of lithium disilicate crystal, lithium phosphate and glass matrix,
      which formed a continuous interlocking structure. The crystal phases were not
      changed before and after hot-pressed treatment. AFM showed nucleating agent
      particles of different sizes distributed on the highly polished ceramic surface.
      The strength and fracture toughness were 300 MPa and 3.1 MPam(1/2). CONCLUSION:
      The high strength and fracture toughness of IPS-Empress 2 glass ceramic are
      attributed to the fine lithium disilicate crystalline, interlocking
      microstructure and crack deflection.

PMID- 15842875
TI  - [A study on transfecting green fluorescent protein gene to rat bone marrow
      mesenchymal stem cells].
AB  - OBJECTIVE: To study an efficient method to transfect green fluorescent protein
      gene (GFP) to rat bone marrow mesenchymal stem cells (MSCs) and to determine the
      biological properties and differentiation potency of transfected MSCs. METHODS:
      SD rats' bone marrow MSCs were separated and purified in vitro. After subculture
      and expansion, MSCs infected with Adenoviral vector (Ad-GFP) or transfected with
      liposome were observed, and their transfection efficiency was assessed with flow
      cytometry. The MSCs expressing GFP gene were induced to differentiate to
      osteoblast, and non-transfected MSCs were set as control. RESULTS: Ad-GFP
      delivered GFP gene with high efficiency to rat MSCs. (41.3 +/- 1.4)% of MSCs
      infected with Ad-GFP expressed GFP gene, which was much higher than the control
      (12.5%). Expression of GFP gene of infected MSCs maintained stable from 1 to 6
      weeks after infection. Infected MSCs possessed the same alkaline phosphatase
      activation as non-infected MSCs, and formed mineralized mouldes. CONCLUSIONS: The
      infected MSCs with Ad-GFP expressed GFP with much higher efficiency than liposome
      transfection, and maintained the same ability of proliferation and
      differentiation as non-infected MSCs. Transfection with Ad-GFP is a highly
      effective method for labeling MSCs.

PMID- 15842876
TI  - [Determination of beta-endorphin in hypothalamus of rat with primary trigeminal
      neuralgia].
AB  - OBJECTIVE: To determine the level and the role of beta-endorphin in hypothalamus
      of rat with trigeminal neuralgia. METHODS: The animal model of primary trigeminal
      neuralgia in rat was established, the contents of beta-endorphin were measured by
      radioimmunoassay techniques. RESULTS: The beta-endorphin of hypothalamus in
      experimental group was significantly lower than other groups (P < 0.01).
      CONCLUSIONS: Beta-endorphin may play important roles in primary trigeminal
      neuralgia.

PMID- 15842877
TI  - [Rights maintenance and self-discipline of practicing dentist: part II. Defect of
      technique in medical dispute].

PMID- 15842878
TI  - [Treatment of periodontol disease: part II. The diagnosis and treatment of
      gingival enlargement].

PMID- 15842881
TI  - [Telescopic denture restoration: part I. Components and retention of telescopic
      denture].

PMID- 15842879
TI  - [Treatment and restoration of residual root and crown: part II. Examination and
      treatment plan for preservation of residual crown and root].

PMID- 15842882
TI  - [Advances in biomarkers of oral premalignant lesions: a review].

PMID- 15842884
TI  - [Adhension-related receptors and genes of Candida albicans].

PMID- 15842886
TI  - [Recent advances in research of genes associated with human tooth agenesis and
      craniofacial malformation syndromes].

PMID- 15842887
TI  - [Segmental mandibular reconstruction by distraction osteogenesis].

PMID- 15842888
TI  - [Classification and choice of surgical procedures for chronic pancreatitis].
AB  - OBJECTIVE: To explore the classification, choice of surgical procedures and the
      clinical outcome of surgical management for chronic pancreatitis. METHODS: 54
      patients with chronic pancreatitis undergoing operation in our hospital from 1983
      to 2004 were analyzed retrospectively, who were divided into chronic calcifying
      pancreatitis and chronic obstructive pancreatitis according to the clinical
      manifestations. RESULTS: There were 41 men (76%) and 13 women (24%) with a mean
      age of 54 years. The cause of chronic pancreatitis was alcohol related in 25
      cases (46%), cholelithiasis in 21 (39%), and previous episodes of acute
      pancreatitis in 18 (33%). Clinical manifestations included abdominal pain in 38
      cases (70%), obstructive jaundice in 27 cases (50%). There existed a significant
      difference in some clinical materials between the two groups of chronic
      calcifying pancreatitis and chronic obstructive pancreatitis, which might mean
      the different pathologic basis in the two kinds of chronic pancreatitis. A total
      of 34 patients underwent nine different operations without perioperative deaths.
      Both the Puestow procedure and the pancreatoduodenectomy was safe and achieved
      pain relief in a large percentage of patients, which could also improve the
      exocrine function whereas the endocrine function remained unchanged. Addition of
      biliary bypass to the Puestow procedure was suitable for the patients with
      stenosis of common bile duct. Jaundice was the main manifestation in the patients
      with the inflammatory mass in the head of the pancreas and Whipple's procedure or
      other resectional procedures should be performed for them. Only drainage of bile
      duct had a better outcome for the relief of jaundice, but its effect to pancreas
      need to be further evaluated. CONCLUSION: The clinicopathologic characteristics
      of obstructive chronic pancreatitis was more variable and the surgical management
      should be also different for individuals.

PMID- 15842889
TI  - [The surgical treatment of the solid-pseudopapillary tumor of pancreas: report of
      21 cases].
AB  - OBJECTIVE: The surgical therapies and prognoses on 21 solid-pseudopapillary
      tumors (SPT) of pancreas were summarized in our center. METHODS: Twenty-one SPTs
      were retrospectively studied and divided into two groups, the complete capsular
      group and the incomplete one. The analyses were performed by SAS6.12 Stat.
      software. RESULTS: There are no tumor recurrences in all patients. There are
      significant difference between operative types in radical resection and the tumor
      position of the pancreas (P = 0.038). There are also significant differences
      between the capsular integrity and the course of the diseases (P = 0.029), and
      the possible malignant cells by the frozen section examination (P = 0.001), and
      the size of the tumor (P = 0.0004). The judgement on the capsular integrity of
      the tumor could directly effect the adoptable operative types (P = 0.001).
      CONCLUSIONS: The surgical resection is good treatment for the SPT, which has
      satisfying prognosis.

PMID- 15842890
TI  - [Evaluation and selection of different procedures in the treatment of pancreatic
      pseudocyst].
AB  - OBJECTIVE: To evaluate the effect of different procedures in the treatment of
      pancreatic pseudocyst. METHOD: This retrospective review analyzed the outcome of
      114 patients with pancreatic pseudocysts managed in PUMC Hospital from January
      1990 to March 2002. RESULT: There were 25 patients without intervention, the
      spontaneous resolution of pseudocysts occurred in 23 of these patients during
      follow up. Twenty-nine cases underwent CT-guided percutaneous catheter drainage;
      the effective rate of therapy was 67.85%. Surgical procedures performed in 60
      cases and the overall mortality was 5% (3/60). The procedures included external
      drainage (8 cases) with 1 death (12.5%), excision (13 cases), cyst-duodenostomy
      (1 cases), cyst-gastrostomy (19 cases) with 7 postoperative gastrointestinal
      bleeding (36.8%) and 1 death (5.26%), Roux-en-Y cyst-jejunostomy (19 cases) with
      3 postoperative gastrointestinal bleeding (15.8%) and 1 death (5.26%).
      CONCLUSIONS: CT-guided percutaneous catheter drainage has the advantage of
      minimal invasive and simple technique; it can be as an effective substitute
      method of traditional open external drainage. Although minimally invasive
      techniques offer a variety of treatment options, surgical procedures are still
      indicated for significant number of patients. The incidence of postoperative
      gastrointestinal bleeding in cyst-gastrostomy was higher than those patients with
      Roux-en-Y cyst-jejunostomy, but most of them were not difficult to treatment, so
      cyst-gastrostomy is still a simple and reasonable procedure for selected
      patients. Excision is a correct choice for cases in which pseudocysts cannot be
      differentiated from neoplastic cysts.

PMID- 15842891
TI  - [Human normal biliary epithelial cells transformation and tumor development
      induced by hepatitis C virus core protein].
AB  - OBJECTIVE: To study the effect of hepatitis C virus core protein (HCV-C) on human
      normal biliary epithelial cells (BEC) transformation and tumor development.
      METHODS: BEC cells were transfected with plasmid pcDNA HCV-C (expressing HCV-C)
      by lipofectamine and selected in G418. The expression of HCV-C gene and protein
      was determined by PCR and immunohistochemical staining, respectively. Biological
      effect of transfected cells was observed through cell proliferation assay, anchor
      independent growth, and tumor development in nude mice. The expression of HCV-C
      protein in the induced tumor was evaluated by immunohistochemistry. RESULTS: HCV
      C was strongly expressed in BEC cells transfected with plasmid pcDNA HCV-C and
      the positive signal was located in cytoplasm. The HCV-C expression protein in the
      induced cytoplasm. Cell proliferation assay showed that the population doubling
      time in the pcDNA HCV-C transfected cells was much shorter than that in the
      pcDNA3 and non-transfected cells (14 h, 28 h, 30 h respectively). The cloning
      efficiencies of transfected cells with pcDNA HCV-C, pcDNA3 and non-transfected
      cells were 36%, 2.5% and 1.5%, respectively (P < 0.01). Tumor developed in nude
      mice inoculated with pcDNA HCV-C transfected cells after the inoculation. HE
      staining showed bile duct carcinoma character and immunohistochemistry confirmed
      HCV-C expression in the tumor tissue. The positive control group also showed
      tumor development, while no tumor mass obtained in the nude mice inoculated with
      pcDNA3 and non-transfected cells even 36 days after the injection. CONCLUSION:
      HCV-C protein showed human normal biliary epithelial cells transformation and
      tumorigenic features.

PMID- 15842894
TI  - [Clinical significance of micrometastasis in lymph nodes and microinvasion in
      primary lesion in submucosal gastric cancer].
AB  - OBJECTIVE: To clarify the clinicopathologic characteristics of micrometastasis in
      lymph nodes and microinvasion in primary lesion for the treatment options with
      regard to submucosal gastric cancer. METHODS: 1945 lymph nodes and 68 primary
      tumors resected from 79 patients with submucosal gastric cancer were examined.
      Two consecutive sections were prepared for simultaneous staining with HE and
      immunostaining with anti-cytokeratin antibody (CAM 5.2), respectively. RESULTS:
      The incidence of nodal involvement in 79 patients with submucosal gastric cancer
      was increased from 13% (10/79 patients) by HE staining to 34% (27/79 patients) by
      cytokeratin immunostaining. Micrometastasis in the lymph nodes were found in 17
      of 69 patients (25%) with cancer-free nodes examined by HE staining.
      Microinvasion to the muscularis properia was found in 11 of 68 patients (16%) who
      were histologically diagnosed as submucosal gastric cancer. Survival analysis
      demonstrated a worse 5-year survival in the patients with micrometastasis in
      lymph nodes (82%) and with microinvasion to muscularis properia (73%). A higher
      incidence of nodal involvement was found in submucosal cancers of large size (> 2
      cm; 43%), a depressed type (48%), lymphatic invasion (73%), and deeper submucosal
      invasion (submucosal 3; 53%). A higher incidence of microinvasion was found with
      the diffused-type carcinoma (33%). CONCLUSIONS: Cytokeratin immunostaining is
      useful for detecting micrometastasis and microinvasion in submucosal gastric
      cancer. Tumor size, microscopic type, lymphatic invasion, and the depth of
      submucosal invasion are strongly associated with lymph node involvement.
      Micrometastasis in lymph nodes and microinvasion in primary lesion indicate an
      unfavorable outcome of the patients with submucosal gastric cancer.

PMID- 15842895
TI  - [The relationship between the expressions of interleukin-8 and cyclooxygenase-2
      and the type of anastomosis in the remnant stomach].
AB  - OBJECTIVE: To study the expressions and the significance of interleukin-8 (IL-8)
      and cyclooxygenase-2 (COX-2) in the remnant stomach. METHODS: Fifty-eight
      patients with gastrectomy were examined by upper gastrointestinal endoscopy. Two
      biopsy specimens were obtained from the stoma and the upper corpus gastric mucosa
      in the remnant stomach. mRNA was extracted from biopsy specimens to measure the
      IL-8 and COX-2 gene mRNA levels by real-time PCR method. RESULTS: IL-8 and COX-2
      levels were higher in stoma than in corpus, IL-8 levels in BI anastomosis were
      significantly higher in stoma than in corpus (P< 0.05). In Hp-negative patients,
      IL-8 and COX-2 levels in stoma were significantly higher in BII anastomosis than
      in BI anastomosis (P < 0.05). In Hp-positive patients, IL-8 and COX-2 levels in
      stoma showed no significant differences between BII anastomosis and BI
      anastomosis. In corpus, IL-8 and COX-2 levels in Hp-positive patients were
      significantly higher than those in Hp-negative patients, (P < 0.05), including in
      BI anastomosis and in BII anastomosis. CONCLUSIONS: The risk of the secondary
      stomach carcinogenesis in stoma after distal gastrectomy is higher than that in
      corpus; The types of anastomosis may influence the risk for the secondary stomach
      carcinogenesis in the remnant stomach mucosa.

PMID- 15842896
TI  - [Relationship between bFGF mRNA and MMP-9 mRNA expression in gastric carcinoma
      and their clinicopathological features as well as patients survival].
AB  - OBJECTIVE: To investigate the mRNA expression of bFGF and MMP-9 in gastric
      carcinomas and to find their correlation with tumor microvascular density (MVD),
      invasion, metastasis and patients survival. METHODS: In situ hybridization and
      immunohistochemistry technique were used to test the expression of bFGF mRNA and
      MMP-9 mRNA and protein of CD34 in 105 specimens of gastric carcinoma. RESULTS: In
      situ hybridization revealed that the positive rates of bFGF mRNA and MMP-9 mRNA
      were 60.95 and 58.1%, respectively; The mean MVD (46.09 +/- 11.52, 43.75 +/-
      13.41 piece/0.72 mm(2)) in tumors with bFGF mRNA and MMP-9 mRNA positive
      expression was significantly higher than that (29.41 +/- 12.47; 33.45 +/- 13.92
      piece/0.72 mm(2)) in tumors with their negative expression, respectively; The
      positive expression rates of bFGF and MMP-9 mRNA were correlated to invasion
      depth (r(s) = 0.211, P = 0.031; r(s) = 0.335, P = 0.001, respectively), growing
      pattern (r(s) = 0.324, P = 0.001; r(s) = 0.267, P = 0.006, respectively), vessel
      invasion (r(s) = 0.579, P = 0.001; r(s) = 0.209, P = 0.032, respectively), lymph
      node metastasis (r(s) = 0.405, P = 0.001; r(s) = 0.343, P = 0.001, respectively)
      and distant metastasis (r(s) = 0.474, P = 0.001; r(s) = 0.468, P = 0.001,
      respectively), but not correlated to tumor type (r(s) = 0.134, P = 0.173; r(s) =
      0.103, P = 0.145, respectively) and differentiation (r(s) = 0.096, P = 0.332;
      r(s) = 0.102, P = 0.298, respectively); And then, the mean MVD in tumors with
      infiltrating type, stage T(3)-T(4), vessel invasion, lymph node metastasis and
      distant metastasis was significantly higher than that in tumors with expanding
      type (t = 10.105, P = 0.001), stage T(1)-T(2) (t = 5.961, P = 0.001), non-vessel
      invasion (t = 7.394, P = 0.001), non-lymph node metastasis (t = 3.819, P = 0.01)
      and non-distant metastasis (r = 10.578, P = 0.001); There was a positive
      relationship between MVD and bFGF mRNA and MMP-9 mRNA (t = 3.207, P = 0.002; t =
      7.035, P = 0.001), respectively; the mean survival time in cases with positive
      bFGF mRNA and MMP-9 mRNA and MVD value >/= 39.5 was significantly shorter than
      that in cases with their negative expression and MVD value < 39.5. CONCLUSIONS:
      bFGF and MMP-9 promote angiogenesis in gastric cancer. Test of the expression of
      bFGF and MMP-9 may act as an useful index to determine angiogenesis, invasion,
      metastasis and patients survival.

PMID- 15842899
TI  - [Release of DNA from Pseudomonas aeruginosa in vitro during spontaneous growth
      and treatment with ciprofloxacin].
AB  - OBJECTIVE: To observe the DNA release from Pseudomonas aeruginosa (P. aeruginosa)
      during spontaneous growth and exposure to different concentrations of
      ciprofloxacin (Cipro) in vitro. METHODS: The P. aeruginosa 1244 strain (ATCC
      27317) was selected because it was sensitive to Cipro in vitro. The minimal
      inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of
      Cipro against this strain were determined, respectively. Different concentrations
      of Cipro were cultured with this strain at 37 degrees C for 4 h and 24 h. The
      samples of culture supernatant were filtered and electrophoresed in 1.8% agarose
      with SYBR Gold stain. Then the images of the gel sheets were photographed.
      RESULTS: The MIC and MBC of Cipro were 0.25 - 0.5 mg/L. The free bacterial DNA in
      4 h culture samples with or without Cipro could not be detected by this method.
      The certain amount of free bacterial DNA molecules in 24 h culture samples
      without antibiotic appeared at the two zones whose molecular weights were more
      than 2000 bp and less than 100 bp. The large amount of free bacterial DNA
      molecules showed at three zones in 24 h culture samples with Cipro when its
      concentrations were much lower than its MIC. In terms of DNA molecular weight,
      the first two zones were above 2000 bp, and the third zone was below 100 bp.
      There was no detectable DNA release from bacteria in 24 h culture samples when
      Cipro was at or above its MIC. CONCLUSIONS: The certain amount of bacterial DNA
      were released from P. aeruginosa in the spontaneous growth. Different
      concentrations of Cipro had quite differential effects on the DNA release from P.
      aeruginosa in quantities and molecular weights in vitro.

PMID- 15842900
TI  - [The use of local flap in repairing deeply burned wound of extremities].
AB  - OBJECTIVE: To discuss a method for reconstruction of deeply burned of
      extremities' functional regions with local skin flaps. METHODS: Ninety-eight
      cases (with 126 place) of deeply burned wound of extremities were reconstructed
      with fasciocutaneous flaps. RESULTS: The survival rate of 162 flaps was 93.2%.
      The movement of 112 joints (88.9%) was restored to normal, and the movement of 14
      joints was mild limitation, none of the cases was severe obstacle. CONCLUSIONS:
      The method is simple and with satisfactory results, which can decrease the rate
      of disability suffered from burn.

PMID- 15842901
TI  - [Role of p38MAPK signal transduction pathway in Kupffer cells production of TNF
      alpha and IL-1beta in severely burned rats].
AB  - OBJECTIVE: To investigate the role of p38 mitogen-activated protein kinase (MAPK)
      signal transduction pathway in the Kupffer cells production of tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-1beta in severely burns rats. METHODS:
      Male health adult Sprague-Dawley rats were randomized into four groups: sham burn
      rats given vehicle, sham burn rats given the p38 MAP kinase inhibitor SB203580,
      rats given a 30% total body surface area (TBSA) full-thickness burn and fluid
      resuscitation plus vehicle, and burn rats given injury and fluid resuscitation
      plus SB203580. Rats from each group were killed at 24 h after burn or sham burn
      and Kupffer cells (KCs) were isolated. After 18 h incubation, KCs next were
      stimulated with 50 ng/ml of LPS for 18 h. After stimulation, supernatants were
      removed for analysis of TNF-alpha and IL-1beta levels by ELISA. The TNF-alpha and
      IL-1beta mRNA expressions (by quantitative real-time RT-PCR) and the activities
      of p38 MAPK and JNK (by Western blot analysis) in KCs were examined. RESULTS:
      Eighteen hours after 50 ng/ml LPS stimulation, KCs from burn rats released
      significantly higher levels of TNF-alpha and IL-1beta than did shams. The mRNA
      levels of TNF-alpha and IL-1beta in KCs increased significantly postburn. Western
      blot analysis suggested that expression of phosphorylated p38 MAPK and JNK were
      increased in KCs harvested from burn group after stimulation with LPS compared
      with those from sham group. In vivo administration of SB203580 markedly
      suppressed both the release of TNF-alpha and IL-1beta and the mRNA expressions of
      TNF-alpha and IL-1beta in KCs from both sham and burn rats. p38 MAPK activity in
      KCs was abolished by administration with SB203580, whereas JNK was not.
      CONCLUSIONS: p38 MAPK signal transduction pathway mediates KCs production of
      proinflammatory cytokines TNF-alpha and IL-1beta in severely burned rats.

PMID- 15842910
TI  - [Surgical correction of post-traumatic kyphosis of thoracolumbar spine].
AB  - OBJECTIVE: To determine the effectiveness of surgical correction for post
      traumatic kyphosis of thoracolumbar spine. METHODS: From 1996 to 2003, 33
      consecutive patients with post-traumatic kyphosis of thoracolumbar spine were
      corrected surgically. The mean age was 40.3 years (range, 13 - 65 years). The
      mean time between the initial injury and surgical correction was 36.0 months
      (range, 6 - 220 months). The kyphotic deformity averaged 40.8 degrees (range, 20
      degrees - 82 degrees ). All the patients had neurological deficits. Twelve
      patients had obvious back pain. Seven patients lost sphincter function completely
      and nineteen patients lost the function partly. Twenty-three patients had ever
      undergone laminectomy and/or instrumentation. The treatment procedure consisted
      of anterior release and posterior spinal osteotomy with instrumentation (15
      patients), posterior closing wedge osteotomy with instrumentation (12 patients),
      anterior release and instrumentation (6 patients). RESULTS: Kyphosis was
      corrected from an average of 40.8 degrees to an average of 5.7 degrees, the
      corrective rate was 86.0% (40.8 degrees - 5.7 degrees /40.8 degrees). There were
      no severe complications. The average follow-up period was 24.6 months (range, 6 -
      84 months). There was no loss of correction at follow-up. Ten of these patients
      showed an improvement in neural function by one or two levels according to the
      classification. Sphincter function recovered partly in ten patients. Back pain
      was relieved significantly in all of twelve patients with back pain
      preoperatively. Bony fusion was achieved in thirty-two patients. One patient had
      nonunion and achieved bony fusion after revision. CONCLUSION: Posterior closing
      wedge osteotomy was suitable to kyphosis less than 40 degrees. Anterior release
      and posterior spinal osteotomy was effective, especially to the patients with
      severe kyphosis deformity or with operation history. Patients with incomplete
      neurological deficits and/or severe back pain could get benefit from osteotomy of
      spine, even if their medical history was long.

PMID- 15842911
TI  - [One-stage radical eradication and wedged vertebral osteotomy through a purely
      posterior procedure in treating thoracic and lumbar spine tuberculosis associated
      with kyphosis or scoliokyphosis demormity].
AB  - OBJECTIVE: To investigate the feasibility, clinical indications and significance
      of one-stage radical eradication, wedged vertebral osteotomy and instrumentation
      in the treatment of tuberculosis of thoracic and lumbar spine associated with
      kyphosis or scoliokyphosis through a purely posterior procedure. METHODS: Sixteen
      cases with tuberculosis of thoracic and lumbar spine associated with kyphosis or
      scoliokyphosis were treated by one-stage radical eradication, wedged vertebral
      osteotomy and instrumentation fixation through posterior procedure. All patients
      included 12 males and 4 females, and the average age was 37.1 years (from 17 to
      53 years). The preoperative average Cobb angle of kyphosis was 78.3 degrees
      (range from 54 degrees to 138 degrees ). There were 2 cases associated with
      scoliosis (the Cobb angle of scoliosis was 31 degrees and 24 degrees), and 1 case
      with lateral transition. Spinal cord compression were found in 7 cases. According
      to the Frankel's classification, 2 cases belonged to C degree, and 5 cases to D
      degree. There were 2 cases with caudal equina or nerve root lesions. RESULTS: The
      average blood loss during the operation was 1100 ml (range from 450 to 2200 ml),
      and the average operation time was 265 min (range from 215 to 325 min). The
      postoperative results were satisfactory, 14 cases were excellent and 2 cases were
      good. Obvious improvement was obtained in 9 cases with neurological dysfunction.
      The postoperative average Cobb' angle was 28.5 degrees (range from 0 degrees to
      67 degrees), and the corrective rate was 63.6%. The followed-up was ranged from
      14 to 52 months with an average of 26.3 months. There were no major complications
      related to the fixations, loss of correction and the fusion were achieved in all
      patients. CONCLUSIONS: One-stage radical eradication, wedged vertebral osteotomy
      and instrumentation is a feasible and an effective procedure in the treatment of
      spinal tuberculosis associated with kyphosis or scoliokyphosis. Compared with
      combined anterior and posterior procedure, the surgical technique may decrease
      injuries and has better result.

PMID- 15842912
TI  - [The efficacy of third-generation instrumentation for the treatment of adult
      scoliosis].
AB  - OBJECTIVE: To evaluate the efficacy of third generation spinal instrumentation
      such as TSRH, CD and ISOLA for the treatment of adult scoliosis. METHODS: Thirty
      five adult scoliosis patients including adult idiopathic and degenerative
      scoliosis were all surgically treated with third generation instrumentation such
      as TSRH, CD and ISOLA from July 1999 to January 2003. Preoperative mean cobb
      angles of major curves of the frontal plane was 58.1 degrees (42 degrees -95
      degrees ). The patients received anterior combined with posterior correction or
      single posterior procedure. Mean follow-up was 20 months (10 - 48 months).
      Preoperative and postoperative Cobb angles of the frontal plane and sagittal
      plane and distance between C(7) and CVSL were measured. We assessed the
      subjective efficacy by questionnaire. RESULTS: Clinical appearance of all
      patients improved significantly. Mean correction of major curves of the coronal
      plane was 53.2%. Mean lost of correction of the coronal plane in the last follow
      up was 4.3 degrees , distance between the midline of C(7) and CVSL was corrected
      from 2.6 cm to 0.24 cm. Questionnaire in the follow-up showed that 89.3% patients
      were satisfied with operation results. Two cases occurred pneumatothorax and
      haematothorax. Three cases still complained about low back pain in 1 year after
      operation, among which 2 were adjacent degeneration and 1 was pseudarthrosis.
      CONCLUSION: Imageology assessment and patients self-evaluation shows that the
      third generation instrumentation could gain good correction and trunk balance in
      the treatment for adult scoliosis. And patients are more satisfied and have less
      complications.

PMID- 15842913
TI  - [The use of lateral mass screws and pedicle screws for the treatment of injury of
      lower cervical spine].
AB  - OBJECTIVE: To discuss the effect of the use of the cervical lateral mass plates
      screws and T(1) pedicle screws for the treatment of C(6) to C(7) injury through
      posterior approach. METHODS: There were 8 patients in the study group; Each of
      them had been injured with low cervical spine C(6) or C(7). There were 6 cases
      with C(6)-C(7) injury and 2 cases with C(7) injury. According to ASIA
      classification, 3 cases were in grade C and 5 cases in D. The lateral mass screws
      were placed on the lateral masses using Margel technique. Lamina or facet bone
      allografting were used to achieve a long-term stability. RESULTS: All 8 patients
      were followed up from 5 to 37 months (mean 15 months). No operative death
      occurred. There were no cord or vertebral artery injury, cerebrospinal fluid
      leak, nerve roots injury, screw malposition or back out, loose of alignment or
      implant failure. Clinical symptom and ASIA classification were improved in all
      patients. Postoperative MRI scanning confirmed satisfactory screw placement in
      all cases. CONCLUSION: This technique is safe and benefit to patients with low
      cervical spine C(6) or C(7) injury.

PMID- 15842914
TI  - [A prospective randomized comparison between with or without instrumentation in
      short-level anterior discectomy and autograft bone fusion].
AB  - OBJECTIVE: To evaluate anterior cervical plating in short-level anterior
      discectomy and autograft bone fusion. METHODS: Eighty-one patients who underwent
      one- and two-level anterior cervical discectomy and fusion were randomized to 2
      groups, with or without instrumentation. Among them, 55 patients were followed
      up. The mean follow-up time was (22 +/- 7) months. Fusion rate, disc height and
      cervical lordotic alignment were assessed by radiographs. RESULTS: The improving
      rates were 68% in non-instrumented group and 58% in instrumented group,
      respectively (P > 0.05). The fusion rate was 93% in the non-instrumented group
      and 100% in the later one. The disc height was decreased (0.7 +/- 1.0) mm in the
      former group and increased (1.2 +/- 0.6) mm in the later one (P < 0.01). Although
      the postoperative cervical lordotic alignment was maintained better in
      instrumented group, the difference was not significant. CONCLUSION: Anterior
      cervical plating can make good influence on the result of anterior cervical
      discectomy and fusion in some degree.

PMID- 15842915
TI  - [Surgical factors underlying the recurrence of primary spine tumor].
AB  - OBJECTIVE: To find the causes of the spinal primary tumors recurrence in surgical
      technique. METHODS: From 1989 to 2002, 38 cases of primary spine tumors,
      including giant cell tumor, osteoblastoma, chondrosarcoma and chordoma with wide
      resection via a piece-meal fashion. By adopting a retrospective method, the
      present study investigated the clinical and imaging materials of pre- and post
      operation period and those in follow-up. RESULTS: The study included 18 cases of
      giant cell tumor, 6 osteoblastoma, 6 chondrosarcoma and 8 chordoma. In all cases,
      63% of tumors were in cervical and cervicothoracic (C(7)-T(2)) spine; 29% in
      thoracolumbar (T(4)-L(5)) spine and 8% in sacrum. Tumors involved in multi
      segment were 34%. And 71% patients had the tumor in the body and the arch
      simultaneously. And 71% of tumors formed paraspinal masses, 42% in both sides.
      The tumors invaded the channel in 58% of the cases. The compartment were invaded
      in 79% patients. Finally, 32 patients were followed up, from 1.0 approximately
      14.9 years, 5.1 years average. Seventeen patients recurred after the surgery, the
      recurrence rate was 53%. The recurrence rate of giant cell tumor was 35%,
      osteoblastoma 50%, chondrosarcoma 75%, chordoma 100%. The recurrence rate of
      tumor in cervical and cervicothoracic spine was 63%, thoracic-lumbar 33%, sacrum
      67%. The recurrence rate of multi-segment tumors was 80%, and that of single
      segment 41%. The recurrence rate of the tumors involving in vertebral body alone
      or involving the arch simultaneously reached 75% and 55% respectively; the
      recurrent rate in the arch alone was 33%. The recurrence rate of the tumors
      involving in vertebral body ranged in different segments. Those growing in
      cervical and cervicothoracic spine reached 73%; those growing in thoracolumbar
      spine was only 25%. The recurrence of the tumors without soft masses was 20%,
      those of single-sided soft masses was 45% and those of double-sided 91%. Among
      the 17 recurrent patients, 83% of the tumors were in the cervical and
      cervicothoracic spine. Those extending to the upper cervical and cervicothoracic
      amounted to 58%. All the 17 recurrent patients had body lesion and paraspinal
      soft masses. CONCLUSIONS: During the primary spinal tumor operation, that failure
      to get adequate exposure and full division is thought to be the cause of
      recurrence. So the precise design before surgery and adequate exposure of the
      tumor in the surgery is the guarantee of wide excision.

PMID- 15842916
TI  - [The surgical palliation of operation combined with vertebroplasty for multiple
      spinal neoplasm].
AB  - OBJECTIVE: To discuss the effect and complication of spinal operation combined
      with vertebroplasty in treating for multiple spinal neoplasm. METHODS: During the
      last two years, 20 patients (13 male and 7 female) with multiple spinal neoplasm
      including metastases, multiple myeloma and lymphoma were treated by operation
      combined with vertebroplasty, 2 vertebral body segments were involved in 5 cases,
      3 to 4 vertebral body segments were involved in 11 cases, more than 5 segments
      were involved in other 4 cases. Neurological function deficit and severe pain
      were seen in all the cases. Patients were evaluated by Tomita prognostic scoring
      system before the operation; The average point was 7.2 (from 3 to 9 points).
      RESULTS: The pain relief rate was 85% (17/20), and neurological recovery was
      found in 10 out of 12 patients who had neurological deficit. According to the
      system of Frankel and neurological function, 1 patient recovered from grade B to
      grade C after the operation, and there was no change in another patients who was
      evaluated as grade A before the operation. The main complication of
      vertebroplasty was leakage of PMMA. Six patients had leakage of PMMA into
      adjacent structures in this series. CONCLUSIONS: Better results of pain relief
      and neurological function recovery and living quality can be achieved by surgical
      palliation of operation combined with vertebroplasty for multiple spinal
      neoplasm.

PMID- 15842917
TI  - [Management of wound infection after spinal operation].
AB  - OBJECTIVE: To elucidate the treatment of wound infection after spinal operation.
      METHODS: Thirty-six cases of wound infection after spinal operation were analyzed
      retrospectively. Sixteen cases had debridement and dressing changing, 20 cases
      had debridement and irrigation-suction system. RESULTS: Thirty-four cases had
      wound healed and 2 case dead of septicemia. Irrigation-suction had better result
      than that of only debridement. Among the 11 cases of internal fixation, 9 cases
      reserved the implants. CONCLUSION: (1) Wound infection after spinal operation is
      a serious postoperative complication and should be treated carefully; (2)
      Nutrition support, reasonable antibiotic and irrigation-suction are effective
      methods; (3) When wound infection occurs, removing the implants out is not
      indispensible.

PMID- 15842918
TI  - [Management of severe pelvic fracture associated with injuries of viscera].
AB  - OBJECTIVE: To probe the approach of emergency management for severe pelvic
      fracture associated with injuries of adjacent viscera and evaluate the
      therapeutic effect. METHODS: The data of 79 patients with severe pelvic fracture
      associated with injuries of adjacent viscera were retrospectively studied, and
      the study covered a period of 14 years. RESULTS: Ligation of internal iliac
      arteries was performed in 33 cases for ceasing massive bleeding due to pelvic
      fracture, and angioembolization in 8. Of 42 patients with cystic or/and urethral
      injury, 35 underwent cystostomy and delayed reconstruction, and 7 received a
      primary realignment. All of 17 patients with injury of retroperitoneal rectum
      underwent diverting colostomy of the proximal end of sigmoid with presacral
      drainage, but 4 received primary repair without colostomy. In 22 patients with
      intraperitoneal colorectal injury, 19 were managed with primary repair or
      anastomosis while 3 received a colostomy. The overall mortality rate was 9%
      (7/79); The main causes were hemorrhagic shock and associated injury. The
      complications included urethro-rectal fistula in 4, thrombosis of right common
      iliac artery in 1, acute respiratory distress syndrome (ARDS) following chest
      trauma in 1, and paraplegia in 1. Except the patient with paraplegia, all of them
      were cured. CONCLUSIONS: Prompt diagnosis and proper treatment were the key of
      the success. Devascularization of internal iliac arteries with external fixation
      cage of pelvis, cystostomy and proximal sigmoidostomy were effective procedures
      frequently used in the emergency treatment of the severe pelvic fracture
      patients.

PMID- 15842919
TI  - [Operative treatment of supracondylar femoral fractures].
AB  - OBJECTIVE: Biomechanical properties between retrograde nail and condylar buttress
      plate for supracondylar femoral fracture were tested and compared. The functional
      operative results were also followed and analyzed. METHODS: (1) Six fresh adult
      moist cadaveric femoral specimens were used to create femoral supracondylar
      fracture models. Six specimens were divided into two groups. Group 1 was fixed
      with retrograde locking intramedullary nail and group 2 with condylar buttress
      plate. All specimens undergone biomechanical test and the data were analyzed
      using SPSS software. (2) From August 1995 to December 2000, 36 cases (37 limbs)
      of femoral supracondylar fracture were included. The follow-up period ranged from
      2.1 years to 7.5 years. RESULTS: (1) Biomechanical tests showed: The stiffness of
      the condylar buttress plate in resisting axial compression force was smaller than
      that of the retrograde locking intramedullary nail. condylar buttress plate
      showed larger stiffness in resisting bending force than the retrograde locking
      intramedullary nail. (2) Clinical outcomes: According to Neer rating system, the
      functional scores were excellent in 26 cases, good in 8, fair in 1 and poor in 2.
      The excellent-good rate was 91.9%. The excellent-good rate of plating cases was
      94.7% and retrograde nail was 93.3%. ROM of the knee joint ranges from 60 degrees
      to 135 degrees , with an average of 110 degrees. CONCLUSION: The excellent or
      good outcomes of femoral supracondylar fracture could be obtained through the
      operative treatment. The fixation of the retrograde locking and condylar buttress
      plate have their own advantages in biomechanical properties.

PMID- 15842920
TI  - [The clinical application and biomechanical study of reconstruction of anterior
      and posterior cruciate ligament with hamstring tendons knot implant fixation].
AB  - OBJECTIVE: To investigate the feasibility of reconstruction of anterior cruciate
      ligament (ACL) and posterior cruciate ligament (PCL) with hamstring tendons knot
      implant fixation. METHODS: Fifty-two cases of ACL and PCL old injury were
      reconstructed under the arthroscopy with double bundles hamstring tendons knot
      implant fixated in the bottle-necked femoral tunnel. The tibia side were fixated
      by tendon weave suture cross tied a knot at the bone bridge of tibia. In this
      group reconstruction of ACL was in 25, PCL and ACL at the same time
      reconstruction in 15, PCL in 12. The failure test and displacement evaluation
      were used to study the biomechanics of reconstruction of ACL by hamstring tendon
      knot implant fixation (n = 13) in porcine knees. The control group were
      reconstructed with bone-patellar tendon-bone B-PT-B and interference screw (n =
      11). The tibia side tendon weave suture immobility by cross tied a knot at the
      tibia bone bridge (n = 7) and interference screw in the tibia tunnel (n = 8).
      RESULTS: Forty-nine cases were followed up, average 14.6 months. The results of
      Lanchman test was negative in 46 cases, positive in 3 cases. Preoperative Lysholm
      score was 56.7, and postoperative was 92.8. According to the knee joint effective
      evaluate standard, 46 were excellent and 3 good. The maximal pull-out force of
      hamstring tendons knot implanted fixation had been greater than B-PT-B fixation
      by interference screw. There were similar displacement in 100 N and 400 N load
      between hamstring tendons knot implant fixation and B-PT-B (P > 0.05). Peak force
      test maximal displacement evaluation and failure energy absorption measurement
      showed that hamstring tendons knot implant fixation was significantly greater
      than B-PT-B (P < 0.01). The failure test and displacement evaluation of tendon
      fixation by weave suture knot at the tibia bone bridge cross tie were greater
      than B-PT-B fixation by interference screw. CONCLUSION: The methods of
      reconstruct of ACL and PCL by hamstring tendons knot implant fixation are
      feasible. The advantages include: it is biological fixation, not machine
      fixation; it may benefit for tendons with bone tunnel healing and decrease
      medical cost. Decreasing or eliminating displacement is helpful to prevent
      relaxation after reconstruction of ACL and PCL.

PMID- 15842921
TI  - [Biomechanical study of flexor tendon repair in an in vivo curvature model].
AB  - OBJECTIVE: To compare the biomechanical characteristics of 2 different repair
      methods:Modified Kessler and Tsuge. METHODS: Eighty-four profound flexor tendons
      of 3(rd) toe of Sanhuang chicken were severed and repaired by either Modified
      Kessler or Tsuge method randomly. Six repaired tendons for each repair method
      were harvested at 0, 1, 4, 7, 10, 14, 21 days after operation and tested in an
      Instron 1185 biomechanical testing machine. An elongation force-elongation
      distance curve was obtained, and biomechanical meters (including rupture force
      and rupture work) were calculated from this curve. RESULTS: Rupture force:
      rupture force significantly decreased at 10(th) and 14(th) day in both repair
      groups, and returned to immediate level at 21(st) day in Modified Kessler group
      but not in Tsuge group; Tsuge method was significantly higher than Modified
      Kessler group at time-points immediately and 7 days after operation. Rupture
      work: this work significantly decreased at 10(th) (65.17 mJ) and 14(th) (40.0 mJ)
      day and resumed to immediate level at 21(st) day in Modified Kessler group; While
      in Tsuge group, it decreased significantly at 14(th) and 21(st) day. Tsuge method
      was significantly higher than Modified Kessler group only at time 0. CONCLUSION:
      The biomechanical properties decrease significantly after 10(th) day at both
      repair method groups. It resumes to immediate level at 21(st) day in Modified
      Kessler group. There is no significant difference after 10(th) day between both
      repair methods.

PMID- 15842922
TI  - [Osteogenesis of rabbit skin fibroblast transfected with core binding factor
      a1/osteoblast specific transplanting factor-2 gene].
AB  - OBJECTIVE: To study osteoblastic phenotype expression of New Zealand rabbit skin
      fibroblasts transfected with mouse core binding factor a1/osteoblast specific
      transplanting factor-2 gene (Cbfa1/Osf2). METHODS: Cbfa1/Osf2 gene, engineered
      into eukaryotic expression vector pSG5, was introduced into New Zealand rabbit
      skin fibroblasts with catholyte liposomes-Lipofectamine 2000. Meanwhile, those
      transfected pSG5 and un-transfected were set the control groups. The expression
      of Cbfa1 gene, osteocalcin (OCN) gene, alkaline phosphatase (ALP) gene and pre
      peptide 2 alpha gene of collagen type I were detected by RT-PCR assay. Cbfa1
      protein was detected by Western-Blot assay, in-cell ALP activity by p-nitrophenyl
      phosphate (PNPP) assay and OCN content in the supernatant by radio-immunity
      method. The ossification nodules was detected by Alizarin-Red staining and
      scanning electron microscope. RESULTS: Cbfa 1mRNA and Cbfa1 protein were
      expressed in New Zealand rabbit skin fibroblasts transfected with pSG5-Cbfa1/Osf2
      from the first day to the fifth day, but they were not detected in the control
      groups. In the pSG5-Cbfa1/Osf2 transfected group, the expression of ALP gene and
      OCN gene were respectively induced from the third day and the forth day, pre
      peptide 2 alpha gene of collagen type I was enhanced from the third day. From the
      sixth day, ALP activity greatly increased, OCN strongly secreted, and they were
      maintained at a high level for about 4 weeks, and the difference was significant
      compared with the control group (P < 0.05). On the forty-second day, ossification
      nodules were found on the surface of pSG5-Cbfa1/Osf2 gene transfected cells.
      CONCLUSIONS: New Zealand rabbit skin fibroblasts transfected with pSG5-Cbfa1/Osf2
      can express osteogenesis-related genes and proteins, and form ossification
      nodules on their surface.

PMID- 15842925
TI  - [Total hip arthroplasty for patients with osteoarthritis secondary to hip
      developmental dysplasia].
AB  - OBJECTIVE: To investigate the methods of restoring normal level of rotation
      center of the hip and limb length in patients with osteoarthritis (OA) secondary
      to developmental dysplasia of the hip (DDH) using total hip arthroplasty (THA).
      METHODS: From January 2000 to January 2003, total hip arthroplasties were
      performed for 21 patients (26 hips) with OA secondary to DDH. There were 19
      females and 2 males with an average age of 51 years (range from 40 to 66 years).
      Based on radiographic classification of Crowe, there were 12 in type I, 5 in type
      II, 2 in type III and IV respectively. In addition to the standard procedure of
      THA, the methods of restoring normal level of rotating center of the hip included
      structural bone autografting and medialization of the cup. The methods of limb
      length restoration included carefully preoperative planning and intraoperative
      soft tissue release. During the follow-up period at 3, 6, 12 months
      postoperatively and then annually thereafter, rotation center of the hip and limb
      length were assessed radiographically. Harris score system (HSS) was used for
      clinical evaluation. RESULTS: All the patients were followed up for a mean time
      of 26.4 months (range from 12 to 48 months). All the patients had restoration of
      the normal level of rotation center of the hip. At the latest follow-up, Harris
      score was improved from preoperative 35 points (range from 12 to 68 points) to
      postoperative 94 points (range from 74 to 100 points). CONCLUSION: In addition to
      standard procedure, the restoration of normal level of rotation center of the hip
      could be achieved by structural bone autografting and medialization of the cup in
      THA for patients with DDH. Careful preoperative planning and intraoperative soft
      tissue release could restore limb length.

PMID- 15842926
TI  - [Sagittal mobility study on the first tarsometatarsal joint in hallux valgus
      patients and its clinical values].
AB  - OBJECTIVE: To study sagittal mobility about the FTJ (first tarsometatarsal joint)
      and its relationship with the pathophysiology and treatment of hallux valgus
      patients. METHODS: According to Lee's method, FTJ sagittal mobility of 300 normal
      feet and 200 hallux valgus was measured, and its correlative factors were
      statistically analysed. RESULTS: FTJ sagittal mobility of 300 normal feet was 8.4
      degrees +/- 2.3 degrees , and that of 200 hallux valgus was 11.7 degrees +/- 3.2
      degrees , the difference was significant. The normal range of FTJ sagittal
      mobility was less than 13 degrees . The sagittal overmotion of FTJ had relation
      to the anatomical configuration of FTJ (P < 0.05), intercuneiform splitting (P <
      0.01), transferred pain under the second metatarsal head (P < 0.01), and FTJ
      osteoarthritis (P < 0.01) had no relation to HVA (hallux valgus angle), IMA
      (intermetatarsal angle), second metatarsus medial diaphyseal cortex hypertrophy
      (P > 0.05). CONCLUSION: Lee's method is convenient and accurate. Both HVA and IMA
      can not represent the sagittal mobility measurement of FTJ, which should be
      routinely evaluated, especially for hallux valgus patients with type I FTJ.
      Lapidus procedure should be considered for patients with larger FTJ in
      combination with transferred pain under the second metatarsal head,
      intercuneiform splitting, FTJ osteoarthritis.

PMID- 15842927
TI  - [Experimental research on human insulin-like growth factor I gene transfect the
      cultured bone marrow mesenchymal stem cells].
AB  - OBJECTIVE: To investigate the effectiveness of human insulin-like growth factor I
      (hIGF-I) gene transferred into the cultured goat bone marrow mesenchymal stem
      cells with liposome, and find a new method of cell-mediated gene therapy.
      METHODS: Bone marrow was extracted from adult goats and cultured in vitro by
      monolayer. Then the recombinant eukaryotic expression plasmid pIRES2-EGFP-hIGF
      was transfected into cells by FuGene 6. After transfection, the marker gene
      coding enhanced green fluorescent protein (EGFP) was observed at different time
      points. The hIGF concentration in the supernatant fluids was measured by enzyme
      linked immunosorbent assay (ELISA) and immunohistochemistry stain of hIGF was
      performed to detect the target protein. Besides, reverse transcription polymerase
      chain reaction and flow cytometry were also adopted in order to find out the
      changes of cells after transfection. RESULTS: Bone marrow stem cells were all in
      the long shuttle-like shape and adhered to the disk. The expression of EGFP was
      first found at 4 h after transfection. The amount and intensity of EGFP increased
      gradually during the period of detection and got to the peak degree at 72 h,
      after that decreased slowly. EGFP was also seen in the second generation cells,
      but the intensity was relatively faint. The IGF-I concentration secreted into the
      supernatant was in accordance with the EGFP observed with the peak concentration
      at 34.75 ng/ml. The outcome of RT-PCR and immunohistochemistry was positive. The
      morphology of many stem cells was changed into triangular or irregular forms
      under the circumstance of the secreted hIGF-I. Percentage of stem cells in the S
      stage increased after transfection. CONCLUSION: The hIGF-I gene can be
      transfected efficiently and safely into BMSCs by FuGene 6, and the hIGF-I protein
      can be secreted into the supernatant in a relatively high level during a long
      period, therefore accelerate the proliferation and differentiation of the
      transfected cells.

PMID- 15842929
TI  - [Expression of CD14 and Toll-like receptor 4 on Kupffer cells and its role in
      ischemia-reperfusion injury on rat liver graft].
AB  - OBJECTIVE: To study the expression of lipopolysaccharide (LPS) receptor CD14 and
      Toll-like receptor 4 (TLR4) on Kupffer cells and its role in ischemia-reperfusion
      injury (IRI) on rat liver graft. METHODS: The Kupffer cells following IRI were
      isolated and divided into control, ischemia-reperfusion (IR), and anti-CD14
      antibody group. The mRNA and protein expression of CD14 and TLR4, nuclear factor
      kappa B (NF-kappaB) activity and TNF-alpha level in supernatant were measured.
      RESULTS: The mRNA and protein expression of CD14 and TLR4 in IR group were
      significantly higher than those in control group (P < 0.01). The NF-kappaB
      activity and TNF-alpha level in IR group were significantly higher than those in
      control group (P < 0.01), and they greatly decreased after anti CD14 antibody
      treatment (compared with IR group, P < 0.05), but were still significantly higher
      than those in control group (P < 0.01). CONCLUSIONS: LPS following IRI could up
      regulate CD14 and TLR4 gene and protein expression on Kupffer cells, and
      subsequently activate NF-kappaB to produce cytokines, but other signal
      transduction pathways might also participate in the IRI.

PMID- 15842930
TI  - [Hypoxia-inducible factor-1 alpha dependent expression and significance of the
      related multidrug resistance genes induced by hypoxia in human hepatocarcinoma
      cell].
AB  - OBJECTIVE: To explore the mechanism of multidrug resistance of hepatocellular
      carcinoma induced by hypoxia and the potential role of hypoxia-inducible factor-1
      alpha (HIF-1 alpha) and multidrug resistance related genes. METHODS: Human
      hepatocarcinoma cell lines HepG2 cells were exposed to hypoxia and were
      transfected by plasmid HIF-1 alpha/PCDNA3, respectively. The expressions of
      multidrug resistance gene (mdr1), multidrug resistance protein (MRP1), and lung
      resistance protein (LRP) gene at the mRNA and the protein levels in the above two
      groups were respectively analyzed by real-time fluorescent quantitative PCR and
      Western-blot technique. RESULTS: In the hypoxia group, the expressions of mdr1,
      MRP1 and LRP were stepped up correlating to the degree of hypoxia, especially the
      prominent increase in the expression of MRP1. Furthermore, they were synchronous
      with the changes of the expression of HIF-1 alpha. Also the increased expression
      of mdr1, MRP1, and LRP gene was observed in transfected HepG2 cells by plasmid
      HIF-1 alpha/PCDNA3. CONCLUSIONS: Resistance of hepatocellular carcinoma to
      chemotherapeutics could be induced by hypoxia. HIF-1 alpha may be critical to the
      upregulation of the expression of the related multidrug resistance genes induced
      by hypoxia. HIF-1 alpha and these related multidrug resistance genes could be
      potential molecular targets for reversing multidrug resistance of hepatocellular
      carcinoma.

PMID- 15842931
TI  - [Downregulation of transforming growth factor-beta1 and platelet-derived growth
      factor gene expression by interleukin-10 in murine hepatic stellate cells in
      response to experimental liver injury].
AB  - OBJECTIVE: To investigate the effect of interleukin-10 (IL-10) on the expression
      of transforming growth factor-beta(1) (TGFbeta(1)) and platelet-derived growth
      factor (PDGF) in hepatic stellate cells (HSC) during liver injury. METHODS: The
      adenovirus vector (the titer was 1 x 10(7) efu/ml) encoded IL-10 gene was used to
      transfect the rat via the vein of caudal. At the same time, CCl(4) was injected
      into rat by a hypodermic injection. These processes went on twice a week. After
      eight weeks, the liver were perfused with collagenase IV and purified by density
      gradient centrifugation with Nycodenz for separate HSC. The level of IL-10 was
      measured by ELISA method; The expression of PDGF and TGFbeta(1) in HSC was
      detected by semi-quantitative RT-PCR and Western-blot methods. RESULTS: The level
      of IL-10 in therapy group (adenovirus vector encoding IL-10 gene group) was
      higher than that in non-therapy group (adenovirus vector without IL-10 gene and
      PBS group); The expression of TGFbeta(1) mRNA, TGFbeta(1) protein and PDGF mRNA,
      PDGF protein in therapy group were significantly lower than that in non-therapy
      group (P < 0.05). CONCLUSION: Downregulating the TGFbeta(1) and PDGF expression
      could be the passageway by which IL-10 alleviate the degree of proliferation and
      activation in hepatic stellate cells.

PMID- 15842934
TI  - [The XbaI and PvuII gene polymorphisms of the estrogen receptor alpha gene in
      Chinese women with breast cancer].
AB  - OBJECTIVE: To investigate the associations of the XbaI and PvuII gene
      polymorphisms in estrogen receptor alpha (ER alpha) gene and breast cancer risk.
      METHODS: Using the method of restrictive fragment length polymorphism, the XbaI
      and PvuII genotypes of ER alpha gene were examined in 138 female breast cancer
      patients and 140 healthy control subjects that age and sex matched. Analyses
      stratified by menopausal status were conducted to check the associations of the
      XbaI and PvuII gene polymorphisms of ER alpha gene and breast cancer risk.
      RESULTS: The frequencies of the XbaI and PvuII alleles of ER alpha gene were
      28.9% for XbaI X allele and 39.6% for P PvuII allele, respectively, in healthy
      Han Chinese. The frequencies of XX and PP genotypes were 4.3% and 15.0%,
      respectively. The frequencies of Xx genotype and carrier with X allele (XX + Xx)
      in breast cancer patients were 34.8% and 39.1%, respectively, significantly lower
      than that in controls with 49.3% and 53.6%, respectively (P = 0.013 and P =
      0.016, respectively). The odds ratio (OR) for heterozygous Xx and carriers with X
      allele (XX + Xx) were 0.538 (95% CI: 0.330 - 0.879) and 0.557 (95% CI: 0.346 -
      0.897), respectively, decreased the breast cancer risk compared with the
      homozygous xx genotype. The decreases in the OR showed to be more significantly
      in the postmenopausal women, OR were 0.366 (95% CI: 0.161 - 0.834) and 0.371 (95%
      CI: 0.167 - 0.823), respectively. No significant difference was showed in the
      PvuII genotype distribution between patients and controls. CONCLUSIONS: The XbaI
      gene polymorphism of ER alpha gene was associated with breast cancer risk, more
      significantly in postmenopausal women. The XbaI X allele could decrease the risk
      of breast cancer. No apparent effect of the PvuII gene polymorphisms of ER alpha
      gene was identified.

PMID- 15842935
TI  - [The effect of breast cancer specific gene 1 in the prognosis of breast cancer].
AB  - OBJECTIVE: To detect breast cancer specific gene 1 (BCSG1) expression in
      different breast tissue, analysis its correlation with clinical parameters and
      evaluate the prognosis of breast cancer. METHODS: The expression of BCSG1 was
      detected by reverse transcription-polymerase chain reaction (RT-PCR) in surgical
      specimens from 84 cases of breast disease patients selected randomly at XinHua
      Hospital affiliated with Shanghai Second Medical University from September 1999
      to December 2002. Of 84 cases, 72 case were breast cancer. Statistic analysis
      BCSG1 gene expression correlation with clinical parameters of breast cancer. 72
      breast cancers were followed up (4 - 43 months) to set up independent prognosis
      factor by survival analysis. RESULTS: BCSG1 was undetectable in all benign breast
      lesions, while was detectable in 36.1% of all breast cancer samples (26/72), in
      which 79.2% of stage III/IV cases were positive (19/24). The expression of BCSG1
      was tightly correlated with the stage (P = 0.000) and the size of tumor (P =
      0.007). Both ER (P = 0.027) and BCSG1 (P = 0.001) were the independent prognosis
      factor of breast cancer. CONCLUSION: BCSG1 is one of independent tumor marker of
      breast cancer, the expression of BCSG1 is closely correlated to the stage of
      breast cancer and the tumor size. Maybe, BCSG1 is a new prognosis factor of
      breast cancer.

PMID- 15842936
TI  - [Exploration of the extent of axillary dissection for patients with node positive
      primary breast cancer].
AB  - OBJECTIVE: To explore the frequency of the involvement of level III and
      interpectoral lymph nodes in patients with node-positive breast cancer, and
      discuss the necessity of completely axillary dissection in this subgroup of
      patients. METHODS: Consecutive 291 cases underwent completely axillary
      dissections (level I/II/III and interpectoral node) according to identical
      procedure. Level I/II, Level III and interpectoral lymph nodes were sent
      separately for routine pathological examination. RESULTS: Eighty-seven cases
      (29.9%) were proved to be node-positive. Among them, metastases were detected at
      level III lymph nodes in 18 cases (20.7%) and at interpectoral lymph nodes in 16
      cases (18.3%), respectively. Twenty-five cases involved in level III and/or
      interpectoral lymph nodes. In a subgroup of 52 cases with primary tumor smaller
      than 5 cm and involved Level I/II lymph nodes less than 4, 6 cases (11.5%) were
      found metastases at level III and/or interpectoral lymph nodes. CONCLUSIONS: It
      is reasonable to perform completely axillary nodes dissection including level III
      and interpectoral lymph nodes for patients with node-positive breast cancer.

PMID- 15842937
TI  - [Surgical treatment of recurrent laryngeal nerve injury caused by thyroid
      operation].
AB  - OBJECTIVE: To study the surgical treatment of recurrent laryngeal nerve (RLN)
      injury caused by thyroid operation. METHODS: From 1970 to 2001, 50 patients with
      RLN injury were caused by thyroid operation. The causes, location, type,
      operative procedures and follow-up were retrospectively analyzed. RESULTS:
      Unilateral RLN injury occurred in 46 cases and bilateral nerve injury in 4 cases.
      The RLN injuries were located within 2cm below the point of RLN entering to
      throat in 45 nerves (83.3%), other places in 6 nerves (11.3%), and unknown
      location in 3 nerves (5.4%). Transection of the nerve was found in 19 nerves
      (36.5%), suture or scare pressing the nerve in 35 nerves (64.8%). All the injured
      nerves were repaired surgically. Meanwhile all 4 patients with bilateral RLN
      injuries underwent tracheotomy. Of the 50 cases, 44 cases (88.0%) were followed
      up for more than 1.5 years. Among the 44 followed-up patients, phonation was
      restored to normal or obvious improvement in 42 cases (95.5%), and improvement in
      2 (4.5%). Of the 35 patients with 39 nerves underwent indirect or direct
      laryngoscopy, the affected vocal cord movement entirely recovered in 21 cords
      (53.8%), partially recovered in 7 cords (17.9%), uncovered in 11 cords (28.3%).
      There was no relation between the recovery of phonation or vocal cord movement
      with the timing or the procedure of repairing operation. CONCLUSIONS: The
      location of most RLN injuries caused by thyroid surgery are just below the point
      of RLN entering to throat, and most are mechanical injury, and need operation to
      resolve the cause. Once the RLN injury is made, an operation should be performed
      as early as possible.

PMID- 15842938
TI  - [A study on polymerase chain reaction site-directed mutagenesis of prepro
      parathyroid hormone in vitro].
AB  - OBJECTIVE: To study PCR site-directed mutagenesis of prepro-parathyroid hormone
      gene in vitro and let furin convert it into mature parathyroid hormone in human
      cells. METHOD: Prepro-parathyroid hormone cDNA of SD rat was cloned from its
      genomic gene and mutated by overlap mutant PCR, introducing furin consensus
      sequences (Arg-Lys-Lys-Arg). An expression pcDNA3.1/mPTH vector encoding a
      genetically modified prepro-parathyroid hormone cDNA was generated, and
      transduced to 293 cells by lipofectin-mediated DNA transfection. Forty-eight and
      72 h after the transfection, the culture media were collected for further assay
      with radioimmunoassay. RESULTS: A fragment of prepro-parathyroid hormone gene was
      cloned and one site were mutated simultaneouly. After screening and sequencing of
      pcDNA3.1/mPTH vectors, a correctly mutated vectors was obtained. While measuring
      parathyroid hormone in the medium of the expressing 293 cells by RIA method, the
      results of transient expression were 28.34 - 52.64 pg/2.0 x 10(6)/cells/Day,
      which were much higher than that in control cells. CONCLUSIONS: A correctly
      mutated prepro-parathyroid hormone cDNA was obtained successfully, transfected,
      and expressed efficiently in human cells.

PMID- 15842940
TI  - [Effect of weight loss induced by laparoscopic adjustable gastric banding on
      immunity of morbid obesity].
AB  - OBJECTIVE: To compare the immunity of morbid obesity (MO) before and after
      laparoscopic adjustable gastric banding (LAGB). METHODS: 15 cases, with a mean
      body mass index (BMI) of 35.8 kg/m(2), were treated by LAGB from Jun. 2003 to
      Oct. 2003 in our department. Patients' immune parameters were determined
      preoperatively and 1, 3 and 6 months postoperatively. 15 cases with a normal BMI
      (23.6 kg/m(2)) were set as controls. RESULTS: Before surgery, the MO had a
      significant lower level of CD(4)(+), CD(4)(+)/CD(8)(+) and a higher level of
      serum interleukin-2 (IL-2), Interleukin-6 (IL-6) than the controls (P < 0.01).
      There was a significant reduction of weight and BMI 6 months postoperatively (P <
      0.01). At the same time, CD(4)(+) increased and serum IL-2 decreased
      significantly. But CD(4)(+)/CD(8)(+)and serum IL-2, IL-6 were still abnormal
      compare to the controls. CONCLUSIONS: MO may combined with an abnormal immunity.
      But after enough weight loss induced by LAGB, it can be partly reversed.

PMID- 15842941
TI  - [Study of immunological effect of dendritic cell transfected with survivin gene
      on the specific anti-alimentary tract tumor].
AB  - OBJECTIVE: To investigate the effects of dendritic cells (DCs) transfected with
      survivin gene, and to observe the effective and specific anti-tumor immunological
      effect induced by modified DC in vitro. METHODS: Survivin gene was transfected to
      DCs with liposomes. Survivin expression could be detected both in DCs cells and
      in cell culture with method of Western blot. Cytokines as well as cellular
      surface molecule such as IL-12, TNF-alpha, CD1 alpha, CD83, MHCII, CD80 and CD86
      were detected. The competence of inducing human specific cytotoxic T lymphocyte
      (CTLs) was also detected with MTT. RESULTS: Survivin expression could be detected
      both in DCs which were transfected with survivin cDNA and in cell culture
      superior. The IL-12 and TNF-alpha level was (265.2 +/- 32.7), (437.1 +/- 83.5)
      pg/ml, and much higher in transgened DC cells than blank DC cells (P < 0.05). CD1
      alpha, CD83, MHCII, CD80 and CD86 was high expressed in survivin-DC cells,
      however, it was low expressed in blank DC cells. The lyse rate to gastric cancer
      cell, colon cancer cell and bile duct cancer cell was 65%, 77%, and 85%
      respectively, and these were much higher than those of blank DC cells.
      CONCLUSIONS: DCs transfected with survivin gene could induce specific cytotoxic T
      lymphocytes and strikingly raised DC cell's antigen present function, and have
      specific CTL killing activity.

PMID- 15842942
TI  - [Mutation detection of mismatch repair genes in hereditary nonpolyposis
      colorectal cancer by denaturing high-performance liquid chromatography].
AB  - OBJECTIVES: To establish DHPLC method in detecting mutations of mismatch repair
      genes, hMLH1 and hMSH2, and to identify germline mutations of hMLH1 and hMSH2 in
      HNPCC kindreds fulfilling Chinese HNPCC criteria. METHODS: Fourteen peripheral
      blood DNA samples from 14 unrelated HNPCC probands fulfilling Chinese HNPCC
      criteria were obtained respectively. PCR amplified 35 exons of two main mismatch
      repair genes, hMLH1 and hMSH2. DHPLC followed by DNA sequencing was used to
      detect and confirm mutations. RESULTS: a total of 41 colorectal cancers and 19
      extracolonic tumors were developed in 14 HNPCC kindreds, and gastric cancer was
      the most common extracolonic tumor type. Twelve single nucleotide changes were
      identified by DHPLC in 14 probands. Among them, three were missense mutations,
      one was a nonsense mutation. Other single nucleotide changes included five single
      nucleotide polymorphisms, two intron single nucleotide changes, one synonymous
      mutation. hMLH1 EXON19 CODON749 TAC-->TAG (Tyr-->X), hMSH2 EXON12 CODON629 CAA-
      >CGA (Gln-->Arg) and hMSH2 EXON15 CODON839 CAT-->CGT (His-->Arg) were new
      discovered mutations. CONCLUSIONS: (1) DHPLC was considered to be highly
      effective, convenient technique with consistent results for the mutation
      detection of hMLH1 and hMSH2 genes. (2) Valid mutations of hMLH1 and hMSH2 genes
      were identified in about one-third HNPCC kindreds fulfilling Chinese HNPCC
      criteria and missense mutation was the most common mutational types in this
      cohort of families.

PMID- 15842944
TI  - [Diagnosis and treatment of tentorial dural arteriovenous fistulae].
AB  - OBJECTIVE: Tentorial dural arteriovenous fistulae are uncommon but life
      threatened lesions. We present our experience of 5 cases with tentorial dural
      arteriovenous fistulae, review the relevant literature and present the rationale
      of our current management strategy. METHODS: The data of five patients with
      tentorial DAVF treated in Huashan Hospital between June 2002 and May 2003 were
      reviewed retrospectively, including their ill history, neuroimagings, operation
      records and follow-up data. RESULTS: There were 3 females and 2 males with age
      from 25 to 52 years (average, 42.6 years). Clinical manifestations were acute
      subarachnoid hemorrhage in 2 cases, progressing neurological deficits in 3 cases.
      MRI and DSA were major diagnostic and follow-up modalities. Borden classification
      type II was in 1 case, type III in 4 cases. According to DAVF location, tentorial
      marginal type were in 3 cases, tentorial lateral type 1 case, tentorial medial
      type 1 case. Two patients had transarterial embolization preoperatively. All
      patients underwent craniotomy with the coagulation of the nidus and tentorium,
      disconnection of leptomeningeal venous drainage. The surgical approaches were via
      trans-anterior-petrous approach in 3 cases, transpterional subdural approach 1
      case, transoccipital and transtentorial approach 1 case. All patients had
      clinical improvement, there was no surgical mortality and morbidity.
      Postoperative DSA confirmed obliteration of DAVF in 3 cases, MRI demonstrated the
      thrombosis of venous aneurysm and the disappearance of previous brainstem edema,
      partial thrombosis of venous aneurysm in 1 case. Follow-up study ranging from 1
      to 2 year showed no recurrence and all patients resume their full activities.
      CONCLUSIONS: Tentorial DAVF is an aggressive vascular lesion, causing
      subarachnoid hemorrhage and progressive neurological deficits. Prompt diagnosis
      and definite treatment for tentorial DAVF are mandatory. Obliteration of the
      nidus and/or leptomeningeal venous drainage should be the goal of treatment.
      Microsurgical procedures with/without endovascular intervention are the best
      choice of treatment.

PMID- 15842945
TI  - [Anatomic research of the subtemporal transpetrosalridge approach].
AB  - OBJECTIVE: Subtemporal transpetrosal ridge approach (STA) was introduced to
      remove the petroclival meningiomas with the simple, safe and minimal invasive
      character. It is suggested to replace the combined approach to reduce the
      morbidity and mortality. METHODS: Surgical anatomic study was done on 10 adult
      cadaver heads fixed in 10% formalin and 10 dry skulls. Ten cadaver heads were
      examined by bone-window CT scan pre and post-operation. The relationships of
      important anatomic structures and positions were measured and photographed.
      RESULTS: For the STA, the important structures include Vein of Labbe, petrous
      bone and brain stem ventral space. The important data include the drilling space
      of the petrous ridge. CONCLUSIONS: STA is an original approach to remove
      petroclival meningiomas. By drilling the petrous ridge, it allows the resecion of
      the tumor simple, safe and minimal invasive. It is suggested to replace the
      combined approach with STA to diminish the morbidity and mortality.

PMID- 15842946
TI  - [Therapeutic evaluation of microvascular decompression in patients with
      trigeminal neuralgia associated with hypertension].
AB  - OBJECTIVE: The aim of work was to evaluate the efficacy of microvascular
      decompression (MVD) in patients with trigeminal neuralgia (TN) associated with
      hypertension. METHODS: Five hundred and thirty-eight cases of TN associated with
      hypertension treated with MVD were retrospectively analyzed, all the cases were
      treated with MVD in the zone of the ventrolateral medulla oblongata and inspected
      postoperative blood pressure. RESULTS: Among 538 cases, 341 cases (63.4%) had
      cure result, 71 cases (13.2%) had obvious effectiveness, 53 cases (9.8%) had
      effectiveness, and 73 cases had no effectiveness. Four hundred and eighty-three
      cases have been followed 1.0 approximately 15.8 years, mean 6.3 years. At the
      time of their follow-up, 313 cases had cure result, 63 cases had obvious
      effectiveness, 42 cases had effectiveness and 65 cases had no effectiveness.
      CONCLUSIONS: It was pathogenesis of nedulla oblongata by abnormal vascular tab,
      long-term aching stimulation and emotional stress. It was an effective method to
      treat TN associated with hypertension with MVD in this zone.

PMID- 15842947
TI  - [Photodynamic diagnosis and fluorescence-guided resection of malignant gliomas: a
      report of 15 cases].
AB  - OBJECTIVE: To study the usefulness of the intraoperative photodynamic diagnosis
      (PDD) and fluorescence-guided resection of malignant gliomas. METHODS: Fifteen
      consecutive patients with malignant gliomas received doses of hematoporphyrin
      derivative (HPD, 2 mg/kg body weight) 48 hours before induction of anesthesia.
      After the tumors recognized by bare eyes they were removed routinely. The
      fluorescence around 690 nm excited by laser beam (wavelength 632.5 nm) was
      detected by laser electronic spectrum analyzer and then fluorescing tissue was
      removed whenever it was considered safel. Tissue samples derived from the walls
      of tumor cavities after resection and PDD were sent for histological examination.
      Compared with the result of the histological examination, the sensitivity and
      specificity of PDD were calculated and recorded. Early postoperative MRI or CT
      were done to determine the extend of the resection of the tumors. Surgical
      mortality and morbidity were also recorded. RESULTS: Intraoperatively, in all of
      15 cases tumor areas with HPD fluorescence could be recognized by laser
      electronic spectrum analyzer. On the basis of 106 tissue samples derived from 15
      tumors, a sensitivity of 90.6%, a specificity of 96.8% and an accuracy of 94.3%
      of PDD were achieved. In 2 cases the resection of residual tumor were performed
      after finding left tumors by PDD. Complete resection of contrast-enhancing tumor
      was accomplished in 9 patients (60%). Residual intraoperative tissue fluorescence
      left unresected for safety reasons predicted residual enhancement on MR images in
      5 of the 6 remaining patients. No perioperative deaths and one case of morbidity
      were encountered. CONCLUSIONS: Intraoperative photodynamic diagnosis following
      resection of malignant gliomas can detect residual tumor tissue with high
      accuracy. Photodynamic diagnosis and fluorescence-guided resection of malignant
      gliomas have a positive role in improving the radicality of malignant glioma
      resection.

PMID- 15842951
TI  - Laparoscopic surgery for inguinal hernia repair: systematic review of
      effectiveness and economic evaluation.
AB  - OBJECTIVES: To determine whether laparoscopic methods are more effective and cost
      effective than open mesh methods of inguinal hernia repair, and then whether
      laparoscopic transabdominal preperitoneal (TAPP) repair is more effective and
      cost-effective than laparoscopic totally extraperitoneal (TEP). DATA SOURCES:
      Electronic databases. Conference proceedings. Manufacturers' submissions to the
      National Institute for Clinical Excellence (NICE) were reviewed. REVIEW METHODS:
      Selected studies were rigorously assessed. Dichotomous outcome data were combined
      using the relative risk method and continuous outcomes were combined using the
      Mantel-Haenszel weighted mean difference method. Time to return to usual
      activities was described using hazard ratios derived from individual patient data
      reanalysis. A review of economic evaluations undertaken by NICE in 2001 was
      updated and an economic evaluation was performed. The estimation of cost
      effectiveness focused on the comparison of laparoscopic repair with open flat
      mesh. A Markov model incorporating the data from the systematic review was used
      to estimate cost-effectiveness for a time horizon up to 25 years. RESULTS: Thirty
      seven randomised control trials (RCTs) and quasi-RCTs met the inclusion criteria
      on effectiveness. Fourteen studies were included in the review of economic
      evaluations. Laparoscopic repair was associated with a faster return to usual
      activities and less persisting pain and numbness. There also appeared to be fewer
      cases of wound/superficial infection and haematoma. However, operation times are
      longer and there appears to be a higher rate of serious complications in respect
      of visceral (especially bladder) injuries. Mesh infection is very uncommon with
      similar rates noted between the surgical approaches. There is no apparent
      difference in the rate of hernia recurrence. Laparoscopic repair was more costly
      to the health service than open repair, with an estimated extra cost from studies
      conducted in the UK of about 300-350 pounds per patient. The point estimates of
      cost provided by the economic model also suggest that the laparoscopic techniques
      are more costly (approximately 100-200 pounds more per patient after 5 years).
      From the review of economic evaluations, the estimates of incremental cost per
      additional day at usual activities were between 86 pounds and 130 pounds. Where
      productivity costs were included, they eliminated the cost differential between
      laparoscopic and open repair. Additional analysis incorporating new trial
      evidence suggested that TEP was associated with significantly more recurrences
      than open mesh but these data did not greatly influence cost-effectiveness.
      CONCLUSIONS: For the management of unilateral hernias, the base-case analysis and
      most of the sensitivity analysis suggest that open flat mesh is the least costly
      option but provides less quality adjusted life years (QALYs) than TEP or TAPP.
      TEP is likely to dominate TAPP (on average TEP is estimated to be less costly and
      more effective). It is likely that, for management of symptomatic bilateral
      hernias, laparoscopic repair would be more cost-effective as differences in
      operation time (a key cost driver) may be reduced and differences in
      convalescence time are more marked (hence QALYs will increase) for laparoscopic
      compared with open mesh repair. When possible repair of contralateral occult
      hernias is taken into account, TEP repair is most likely to be considered cost
      effective at threshold values for the cost per additional QALY above 20,000
      pounds. The increased adoption of laparoscopic techniques may allow patients to
      return to usual activities faster. This may, for some people, reduce any loss of
      income. For the NHS, increased use of laparoscopic repair would lead to an
      increased requirement for training and the risk of serious complications may be
      higher. Chronic pain should now be addressed prospectively using standard
      definitions and allowing assessment of the degree of pain. More evidence is
      required on the loss of utility caused by persisting pain and numbness, as well
      as serious complications resulting from minor surgery. Prospective population
      based registries of new surgical procedures may be the best way to address this,
      as a complement to randomised trials assessing effectiveness. Further research
      relating to whether the balance of advantages and disadvantages changes when
      hernias are recurrent or bilateral is also required as current data are limited.
      Methodologically sound RCTs are needed to consider the relative merits and risks
      of TAPP and TEP. Further methodological research is required into the complexity
      of laparoscopic groin hernia repair and the improvement of performance that
      accompanies experience.

PMID- 15842952
TI  - Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for
      epilepsy in adults: a systematic review and economic evaluation.
AB  - OBJECTIVES: To examine the clinical effectiveness, tolerability and cost
      effectiveness of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV),
      oxcarbazepine (OXC), tiagabine (TGB), topiramate (TPM) and vigabatrin (VGB) for
      epilepsy in adults. DATA SOURCES: Electronic databases. Internet resources.
      Pharmaceutical company submissions. REVIEW METHODS: Selected studies were
      screened and quality assessed. Separate analyses assessed clinical effectiveness,
      serious, rare and long-term adverse events and cost-effectiveness. An integrated
      economic analysis incorporating information on costs and effects of newer and
      older antiepileptic drugs (AEDs) was performed to give direct comparisons of long
      term costs and benefits. RESULTS: A total of 212 studies were included in the
      review. All included systematic reviews were Cochrane reviews and of good
      quality. The quality of randomised controlled trials (RCTs) was variable.
      Assessment was hampered by poor reporting of methods of randomisation, allocation
      concealment and blinding. Few of the non-randomised studies were of good quality.
      The main weakness of the economic evaluations was inappropriate use of the cost
      minimisation design. The included systematic reviews reported that newer AEDs
      were effective as adjunctive therapy compared to placebo. For newer versus older
      drugs, data were available for all three monotherapy AEDs, although data for OXC
      and TPM were limited. There was limited, poor-quality evidence of a significant
      improvement in cognitive function with LTG and OXC compared with older AEDs.
      However, there were no consistent statistically significant differences in other
      clinical outcomes, including proportion of seizure-free patients. No studies
      assessed effectiveness of AEDs in people with intellectual disabilities or in
      pregnant women. There was very little evidence to assess the effectiveness of
      AEDs in the elderly; no significant differences were found between LTG and
      carbamazepine monotherapy. Sixty-seven RCTs compared adjunctive therapy with
      placebo, older AEDs or other newer AEDs. For newer AEDs versus placebo, a trend
      was observed in favour of newer drugs, and there was evidence of statistically
      significant differences in proportion of responders favouring newer drugs.
      However, it was not possible to assess long-term effectiveness. Most trials were
      conducted in patients with partial seizures. For newer AEDs versus older drugs,
      there was no evidence to assess the effectiveness of LEV, LTG or OXC, and
      evidence for other newer drugs was limited to single studies. Trials only
      included patients with partial seizures and follow-up was relatively short. There
      was no evidence to assess effectiveness of adjunctive LEV, OXC or TPM versus
      other newer drugs, and there were no time to event or cognitive data. No studies
      assessed the effectiveness of adjunctive AEDs in the elderly or pregnant women.
      There was some evidence from one study (GBP versus LTG) that both drugs have some
      beneficial effect on behaviour in people with learning disabilities. Eighty RCTs
      reported the incidence of adverse events. There was no consistent or convincing
      evidence to draw any conclusions concerning relative safety and tolerability of
      newer AEDs compared with each other, older AEDs or placebo. The integrated
      economic analysis for monotherapy for newly diagnosed patients with partial
      seizures showed that older AEDs were more likely to be cost-effective, although
      there was considerable uncertainty in these results. The integrated analysis
      suggested that newer AEDs used as adjunctive therapy for refractory patients with
      partial seizures were more effective and more costly than continuing with
      existing treatment alone. Combination therapy, involving new AEDs, may be cost
      effective at a threshold willingness to pay per quality-adjusted life year (QALY)
      greater than 20,000 pounds, depending on patients' previous treatment history.
      There was, again, considerable uncertainty in these results. There were few data
      available to determine effectiveness of treatments for patients with generalised
      seizures. LTG and VPA showed similar health benefits when used as monotherapy.
      VPA was less costly and was likely to be cost-effective. The analysis indicated
      that TPM might be cost-effective when used as an adjunctive therapy, with an
      estimated incremental cost-effectiveness ratio of 34,500 pounds compared with
      continuing current treatment alone. CONCLUSIONS: There was little good-quality
      evidence from clinical trials to support the use of newer monotherapy or
      adjunctive therapy AEDs over older drugs, or to support the use of one newer AED
      in preference to another. In general, data relating to clinical effectiveness,
      safety and tolerability failed to demonstrate consistent and statistically
      significant differences between the drugs. The exception was comparisons between
      newer adjunctive AEDs and placebo, where significant differences favoured newer
      AEDs. However, trials often had relatively short-term treatment durations and
      often failed to limit recruitment to either partial or generalised onset
      seizures, thus limiting the applicability of the data. Newer AEDs, used as
      monotherapy, may be cost-effective for the treatment of patients who have
      experienced adverse events with older AEDs, who have failed to respond to the
      older drugs, or where such drugs are contraindicated. The integrated economic
      analysis also suggested that newer AEDs used as adjunctive therapy may be cost
      effective compared with the continuing current treatment alone given a QALY of
      about 20,000 pounds. There is a need for more direct comparisons of the different
      AEDs within clinical trials, considering different treatment sequences within
      both monotherapy and adjunctive therapy. Length of follow-up also needs to be
      considered. Trials are needed that recruit patients with either partial or
      generalised seizures; that investigate effectiveness and cost-effectiveness in
      patients with generalised onset seizures and that investigate effectiveness in
      specific populations of epilepsy patients, as well as studies evaluating
      cognitive outcomes to use more stringent testing protocols and to adopt a more
      consistent approach in assessing outcomes. Further research is also required to
      assess the quality of life within trials of epilepsy therapy using preference
      based measures of outcomes that generate cost-effectiveness data. Future RCTs
      should use CONSORT guidelines; and observational data to provide information on
      the use of AEDs in actual practice, including details of treatment sequences and
      doses.

PMID- 15842953
TI  - Nasal cytokines as mediators of illness during the common cold.
AB  - Identification of a pharmacologically targeted mediator of the common cold is a
      desirable, but, to date, elusive goal of current research. The roles of various
      mediators, such as histamine, leukotrienes, bradykinin, and, more recently,
      chemokines and cytokines, in the pathophysiology and development of complications
      of the common cold are the subject of previous and current investigations.
      Establishing causality of a mediator in the common cold has been difficult for a
      number of reasons, including the limitations of our research tools and protocols
      and the complexity of the inflammatory and immune pathways that participate
      during the common cold. The available evidence for mediation of the common cold
      is the subject of this manuscript.

PMID- 15842954
TI  - Immunostimulatory sequences of DNA and conjugates in the treatment of allergic
      rhinitis.
AB  - Therapeutic strategies based on the use of immunostimulatory sequences of DNA
      containing a CpG motif (also known as ISS DNA, or CpG DNA) are focused on
      minimizing the allergenicity of immunotherapy while improving its effectiveness.
      Several ISS DNA-based methods of immunization (ISS DNA alone, ISS DNA conjugated
      to a protein allergen) have shown promise in animal models of asthma, and some of
      these ISS DNA-based therapies have entered clinical trials. These ongoing
      clinical trials will help to determine whether any of these ISS DNA-based
      therapies are safe and effective to use in subjects with allergic rhinitis and
      asthma.

PMID- 15842955
TI  - Antigen-independent effects of immunoglobulin E.
AB  - Immunoglobulin E (IgE) is an important mediator in immediate hypersensitivity, as
      it facilitates mast cell degranulation and the release of immunomodulatory
      mediators, such as histamine, prostaglandins, and cytokines. Antigen-specific IgE
      is a hallmark of allergic diseases. Upon interaction with polyvalent antigen, IgE
      molecules crosslink and transmit signals that drive this process. Recently, an
      alternative function of IgE has come to light. Rather than merely priming the
      mast cell, in the absence of antigen, IgE influences mast cells, including their
      survival, receptor expression, and mediator release. The mechanisms by which IgE
      induces these effects and the biological consequences are being discovered and
      are showing that IgE has an important and active role in facilitating immune
      responses.

PMID- 15842956
TI  - The immunoglobulin E receptor: expression and regulation.
AB  - The interaction of immunoglobulin E (IgE) and its receptors is critical for the
      manifestation of allergic disease. Currently, IgE receptors include the high
      affinity Fc epsilonRI and the low-affinity Fc epsilonRII. Fc epsilonRI is a
      tetrameric or trimeric complex, and each has distinct expression patterns and
      unique functional consequences. In general, serum levels of IgE regulate Fc
      epsilonRI expression, and novel therapies that lower the concentration of IgE
      have provided insights into the contribution of this receptor in allergic
      disease. Newer therapies targeting Fc epsilonRI-signaling elements and the low
      affinity IgE receptor, Fc epsilonRII (CD23), are being developed.

PMID- 15842957
TI  - Genetically engineered vaccines.
AB  - The application of recombinant DNA technology to allergen research has provided
      the sequence information and genetic material to produce new types of allergy
      vaccines. One general strategy has been to use the knowledge to produce synthetic
      peptides that represent selected T-cell or B-cell epitopes. The production of
      genetically engineered allergens provides an alternative strategy to construct
      hypoallergenic vaccines, which can provide a better and less selected
      representation of the epitopes. Many strategies have been used to produce such
      hypoallergens, and their ability to reduce allergenicity has been amply
      demonstrated by skin and nasal provocation tests. The retention of T cell
      stimulating activity has also been demonstrated, and a consistent feature of the
      vaccines has been, despite the reduced immunoglobulin E (IgE)-binding reactivity,
      the ability to induce anti-allergen IgG antibody. The lead hypoallergens have
      been polypeptide fragments and trimeric constructs of the birch allergen Bet v 1.
      A clinical trial with these medicaments has shown the ability to modify IgE and
      IgG antibody production, skin test reactivity, and symptom scores. This is the
      first trial of a recombinant allergy vaccine, and it has set a benchmark for
      further studies. A new generation of hypoallergens is now being produced based on
      the detailed knowledge of the tertiary structures of the allergens and of the T
      cell and B-cell epitopes. The modifications have been made to change the
      topography of the allergens while retaining a stable, folding structure. In the
      case of Bet v 1, tertiary structures of hypoallergens have been determined.
      Structurally modeled hypoallergens have been produced for pollen, venom, food,
      and latex allergens, with promising characteristics from preclinical studies.

PMID- 15842958
TI  - Neurotrophin effects on eosinophils in allergic inflammation.
AB  - Elevated neurotrophin concentrations have been shown in nasal and bronchoalveolar
      lavage fluids as well as in the sera of patients with allergic rhinitis and
      asthma. Concentration of nerve growth factor correlated with disease severity,
      bronchial hyperreactivity, and levels of mediators released from eosinophils. Due
      to the release of cationic proteins, oxygen species, and cytokines after
      degranulation, eosinophils contribute to tissue damage and can influence airway
      hyperresponsiveness in asthma. It has been hypothesized that neurotrophins may be
      involved in the development of eosinophilia and in activation of these cells. The
      aim of this review is to elucidate the direct and indirect mechanisms of
      neurotrophins contributing to eosinophilia in allergic diseases.

PMID- 15842959
TI  - Pets and the development of allergic sensitization.
AB  - Sensitization to pets remains a risk factor for asthma and rhinitis, and can
      occur in people who have never lived with a pet. Several reports have indicated
      that living with a pet reduces the risk for becoming sensitized to that pet.
      Having a pet in the home gives exposure to more than just allergens. In areas
      with high frequency of pet ownership, community exposure to pet allergens is
      almost certainly sufficient to induce sensitization among non-pet owners. In this
      review, we examine the results of recent studies that have investigated the
      relationship between pet ownership, specific sensitization to that pet, and
      allergic sensitization in general. For cat ownership, the results are
      inconsistent between studies of similar design, with some studies suggesting an
      increase in risk and others a decrease among cat owners. For dogs, results are
      more consistent, generally suggesting that owning a dog has no effect or indeed
      may be protective against the development of specific sensitization to dog and
      allergic sensitization in general.

PMID- 15842960
TI  - Potential roles in rhinitis for protease and other enzymatic activities of
      allergens.
AB  - Exposure to airborne pollen, fungal allergens, and dust mite allergens is
      associated with the development of allergic rhinitis. Biologic function of
      allergens is considered to be a key determinant for allergenicity, and many
      clinically important allergens have been shown to possess enzymatic activity. It
      is proposed that by enabling allergens to breach the integrity of the airway
      epithelial barrier, proteolytic activity plays an adjuvant pro-allergic role
      influencing immunogenicity. In this review, current evidence regarding enzymatic
      activity of aeroallergens is described, and the potential role of aeroallergens
      in allergic rhinitis is discussed.

PMID- 15842961
TI  - A new paradigm for immunoglobulin E in allergic diseases.
AB  - Recent observations at the level of the antigen presenting cell, as well as the T
      cell, point toward a pivotal role for interleukin (IL)-10 in the control of
      immunoglobulin E (IgE)-mediated allergic diseases, such as asthma and rhinitis.
      This has led to restructuring of the Th1/Th2 paradigm with IL-10 acting to
      modulate Th2-driven IgE antibody (Ab) responses. The modified Th2 response to cat
      allergen is associated with high-dose allergen exposure and the presence of high
      titer IgG and IgG4 Ab; however, IgE Ab and allergic symptoms are absent.
      Characteristics of this immune response indicate that it is a variant of the
      allergic response, which develops in an IL-10-dependent manner, but it is
      distinct from other types of nonallergic or tolerant responses. These
      observations point toward a new paradigm for the development of IgE-mediated
      responses. This may be important for advancing our understanding of the response
      to immunotherapy and anti-IgE, and for defining immune mechanisms that drive
      allergic responses.

PMID- 15842962
TI  - Persistent nonallergic rhinosinusitis.
AB  - Nonallergic rhinitis is a complex of syndromes that are united by the absence of
      atopic, T(H)2 lymphocyte, immunoglobulin E (IgE)-mediated mechanisms. We propose
      a classification system based on the presence or absence of inflammatory
      granulocytes. Eosinophilic nonallergic rhinosinusitis may also be called chronic
      eosinophilic sinusitis syndromes (CESS) to help classify these disorders in which
      diverse mechanisms of eosinophil chemoattraction and survival predominate.
      Allergic fungal sinusitis, eosinophilic nasal polyps, aspirin sensitivity, and
      related disorders would fit in this category. Accumulation of neutrophils occurs
      in chronic infectious rhinosinusitis, foreign body reactions, and
      immunodeficiencies. More complex and variable combinations of leukocytes are
      found in Wegner's granulomatosis and related syndromes, and during the evolution
      of viral infections. The noninflammatory disorders can be divided by mechanism
      into hormonal; sympathetic dysfunction (including antihypertensive adrenergic
      drug therapy); cholinergic rhinitis; and nociceptive syndromes with hyperalgesia
      and other features (eg, the nonallergic rhinitis of chronic fatigue syndrome).
      Therapy based on the most likely pathophysiologic mechanism is anticipated to
      have the most success, but requires acceptance of the wide differential diagnosis
      of nonallergic rhinitis and rejection of the obsolete term of "vasomotor
      rhinitis."

PMID- 15842963
TI  - Therapeutic approaches to mucus hypersecretion.
AB  - Mucolytic and related agents have been in use since prehistoric times. Although
      widely prescribed and used extensively in over-the-counter preparations, their
      efficacy and mechanisms of action remain in doubt. These agents belong to several
      distinct chemical classes. Mucolytic agents such as N-acetyl-cysteine are thiols
      with a free-sulfhydryl group. They are assumed to break disulfide bonds between
      gel-forming mucins and thus reduce mucus viscosity. Mucokinetic agents are thiols
      with a blocked sulfhydryl group. Expectorants such as guaifenesin increase mucus
      secretion. They may act as irritants to gastric vagal receptors, and recruit
      efferent parasympathetic reflexes that cause glandular exocytosis of a less
      viscous mucus mixture. Cough may be provoked. This combination may flush
      tenacious, congealed mucopurulent material from obstructed small airways and lead
      to a temporary improvement in dyspnea or the work of breathing. The roles of
      anticholinergic agents, DNase, and other drugs are also discussed with regard to
      their roles in reducing mucus production in rhinitis and other airway diseases.

PMID- 15842964
TI  - The role of immunoglobulin E and immune inflammation: implications in allergic
      rhinitis.
AB  - Immunoglobulin E (IgE) plays a critical role in the allergic inflammatory process
      in diseases such as allergic rhinitis. Cross-linking IgE bound to its receptor on
      cells by multivalent allergens initiates a chain of events resulting in allergic
      immune responses. Mast cells and basophils are involved in the early, immediate
      response, which is marked by cellular degranulation and the release of
      proinflammatory mediators, including histamine. Antigen-presenting cells are also
      activated by allergen-loaded IgE, resulting in immunomodulation of T-cell
      responses. The IgE molecule binds to two types of receptors, the high-affinity
      (Fc epsilonRI) and low-affinity (Fc epsilonRII or CD23) receptors, that have
      differing properties important in mediating allergen-induced responses. New
      therapies targeting the IgE molecule reduce allergen-stimulated immune responses
      and improve the clinical symptoms in subjects with allergic rhinitis.
      Understanding the role of the IgE molecule is necessary to appreciate the
      development and use of novel therapies targeting its actions.

PMID- 15842965
TI  - Effects of atorvastatin versus other statins on fasting and postprandial C
      reactive protein and lipoprotein-associated phospholipase A2 in patients with
      coronary heart disease versus control subjects.
AB  - The effects of atorvastatin (40 mg/day) versus placebo on fasting and
      postprandial plasma levels of high-sensitivity C-reactive protein (hs-CRP) and
      lipoprotein-associated phospholipase A2 (Lp-PLA2) were examined over 36 weeks in
      84 patients who had coronary heart disease and low-density lipoprotein
      cholesterol levels >130 mg/dl and compared directly with the effects of
      fluvastatin, lovastatin, pravastatin, and simvastatin. Results were also compared
      with those obtained in age- and gender-matched control subjects (n = 84). Feeding
      increased median hs-CRP levels by 2% in patients (p = NS) and 22% in controls (p
      <0.01) and increased mean Lp-PLA2 values by 9% in patients (p = NS) but decreased
      values by 21% in controls (p <0.0001). Patients had 51% higher median hs-CRP
      values and 29% higher mean Lp-PLA2 values than did controls (p <0.05 for hs-CRP
      and Lp-PLA2) in the fasting state; however, Lp-PLA2 values were 62% higher (p
      <0.0001) in the fed state in patients compared with controls. Atorvastatin
      decreased median hs-CRP levels by 32% (p <0.01) and mean Lp-PLA2 values by 26% in
      patients (p <0.0001), with similar decreases in the fed state, and none of the
      other statins had any significant effect on these parameters. Change in Lp-PLA2
      was significantly related to change in low-density lipoprotein cholesterol (p
      <0.01), with no significant relations with change in hs-CRP. Our data indicate
      greater differences in patients with coronary heart disease compared with
      controls in Lp-PLA2 in the fed state than in the fasting state and that
      atorvastatin is more effective than fluvastatin, lovastatin, pravastatin, or
      simvastatin for decreasing not only low-density lipoprotein cholesterol but also
      hs-CRP and Lp-PLA2.

PMID- 15842966
TI  - Usefulness of real-time myocardial perfusion imaging to evaluate tissue level
      reperfusion in patients with non-ST-elevation myocardial infarction.
AB  - Microvascular integrity is a prequisite for functional recovery in patients who
      have myocardial infarction after recanalization of the infarct-related coronary
      artery. In this study, we investigated whether impaired myocardial perfusion is
      present in patients who have non-ST-elevation myocardial infarction and whether
      the extent and time course of myocardial tissue reperfusion as assessed by
      myocardial contrast echocardiography (MCE) are related to functional recovery.
      Consecutive patients (n = 32) who presented with a first non-ST-elevation
      myocardial infarction were included in our study. MCE was performed on admission,
      1 to 4 hours after angioplasty, and at 24 hours, 4 days, and 4 weeks of follow
      up. Contrast images were analyzed visually and quantitatively. Myocardial blood
      flow was estimated by calculating the product of peak signal intensity and the
      slope of signal intensity increase. Improvement of wall motion on follow-up
      echocardiograms after 4 weeks served as a reference for functional recovery of
      impaired left ventricular function. Of 496 segments available for analysis, 128
      (26%) were initially dysfunctional and 96 (75%) recovered at 4 weeks of follow
      up. Myocardial tissue reperfusion occurred gradually, expanding over the first 24
      hours after percutaneous coronary intervention (myocardial blood flow of 0.4 +/-
      0.3 initially, 0.6 +/- 0.4 at 24 hours, and 1.6 +/- 0.7 dB/s at 4 weeks of follow
      up, p <0.001). Extent of tissue reperfusion was closely related to grade of
      improvement of global ejection fraction (r2 = 0.76, p <0.001). MCE predicted
      functional recovery with a sensitivity of 81%, a specificity of 88%, and accuracy
      of 83% on a segmental level. Thus, impaired microvascular integrity is suggested
      by MCE in patients who present with non-ST-elevation myocardial infarction.
      Improvement of regional tissue perfusion after revascularization is closely
      related to functional recovery. This information may aid risk stratification and
      allow monitoring of the effectiveness of reperfusion therapy in these patients.

PMID- 15842967
TI  - Usefulness of tissue Doppler imaging in the diagnosis and prognosis of acute
      right ventricular infarction with inferior wall acute left ventricular
      infarction.
AB  - Tissue Doppler (TD) imaging is a novel echocardiographic technique that measures
      myocardial velocities. However, there are sparse data on TD imaging of the right
      ventricular (RV) free wall in the diagnosis and prognosis of RV myocardial
      infarction (MI) in inferior wall left ventricular MI. Fifty patients who had left
      ventricular MI underwent TD echocardiography and angiography within 48 hours of
      MI. For diagnosis, the ability of RV TD imaging to detect RV MI was assessed
      using coronary angiography as the reference standard. For prognosis, the ability
      of TD detection of RV dysfunction to predict cardiac death or rehospitalization
      at 1 year was determined. For diagnosis, the univariate predictors of RV MI
      included RV diastolic dimension (p = 0.001), TD imaging of tricuspid annular
      systolic velocity (p = 0.001), and early diastolic velocity (p = 0.002). On
      multivariate analysis, systolic annular velocity (p = 0.04) and RV dimension (p =
      0.05) predicted RV MI. For prognosis, nonculprit coronary artery disease (p =
      0.003), TD imaging of RV systolic annular velocity (p = 0.005), and early
      diastolic velocity (p = 0.01) were among the univariate predictors of cardiac
      death or rehospitalization. On multivariate analysis, nonculprit coronary artery
      disease (p = 0.02) and TD imaging of systolic annular velocity (p = 0.04) were
      independent predictors of outcome. Decreased RV systolic annular velocity on TD
      images detects RV MI in first left ventricular acute inferior MI and predicts
      cardiac death or rehospitalization at 1 year.

PMID- 15842968
TI  - Influence of stent length to lesion length ratio on angiographic and clinical
      outcomes after implantation of bare metal and drug-eluting stents (the TAXUS-IV
      Study).
AB  - Longer bare metal stent lengths have been associated with greater restenosis.
      However, the effect of the ratio of stent length to lesion length on clinical and
      angiographic restenosis after implantation of bare metal and drug-eluting stents
      has not been clearly defined. Patients in the TAXUS-IV study who underwent single
      study stent placement were categorized into tertiles based on ratios of stent
      length to lesion length. Clinical results at 1 year and angiographic outcomes at
      9 months were compared across the 3 groups. The median ratios of stent length to
      lesion length were 1.20, 1.58, and 2.27 in the 3 tertiles. Analysis segment
      restenosis rates at 9 months were similar across the 3 tertiles with bare metal
      stents (24.7% vs 26.7% vs 23.8%, respectively, p = 0.90 for trend) and paclitaxel
      eluting stents (11.7% vs 6.5% vs 5.4%, respectively, p = 0.24). Similarly, there
      were no differences in 1-year rates of target lesion revascularization across the
      3 tertiles for bare metal stents (14.6% vs 14.8% vs 13.7%, respectively, p =
      0.91) or paclitaxel-eluting stents (6.1% vs 3.6% vs 4.0%, respectively, p =
      0.38). By multivariate analysis, the ratio of stent length to lesion length was
      an independent predictor of neither 9-month angiographic restenosis nor 1-year
      target lesion revascularization in the bare metal stent arm (odds ratio 1.21, p =
      0.36, and hazard ratio 0.80, p = 0.31, respectively) or in the paclitaxel-eluting
      stent arm (odds ratio 0.86, p = 0.76, and hazard ratio 0.58, p = 0.21,
      respectively). These data do not support the arbitrary use of larger ratios of
      stent length to lesion length in patients who undergo implantation of drug
      eluting stents.

PMID- 15842969
TI  - Comparison of the relation of triglyceride-rich lipoproteins and muscular artery
      compliance in healthy women versus healthy men.
AB  - To determine whether structural features or concentrations of plasma lipoproteins
      are predictive of arterial compliance in healthy women versus healthy men,
      cohorts of 111 men and 112 women with a wide range of 10-year risks for coronary
      artery disease were selected using assessments based on the Framingham Heart
      Study. Age ranges were restricted to 35 to 69 years for men and 45 to 79 years
      for women. Lipid-lowering drugs or any evidence of vascular disease was cause for
      exclusion. Fasting lipoprotein analysis and arterial compliance measurements in
      thigh and calf were completed in all patients. Plasma triglyceride levels were
      the most powerful predictor of compliance in women. Weaker but significant
      relations were observed between plasma non-high-density lipoprotein cholesterol,
      apolipoprotein-B, and apolipoprotein-CIII. In contrast, the only significant
      predictor of compliance in men was body weight. Thus, the major lipid predictors
      of arterial stiffness in women are concentrations of triglyceride-rich
      lipoproteins. These results are consistent with previous findings that
      triglyceride measurements are more strongly related to clinical vascular events
      in women than in men.

PMID- 15842970
TI  - Comparison of autotriggered memory loop recorders versus standard loop recorders
      versus 24-hour Holter monitors for arrhythmia detection.
AB  - To determine the relative yields of Holter monitoring (HM), memory loop recording
      (MLR), and autotriggered MLR (AT-MLR), we retrospectively interrogated the very
      large database of Lifewatch (a Card Guard company and a commercial monitoring
      company) and compared the results obtained by each method. From among a total
      database of approximately 100,000 patients, records of 1,800 patients from 2003
      were randomly selected and examined, 600 from each of the 3 different monitoring
      groups. Each session of MLR and AT-MLR was applied for 30 days. For each patient
      we determined the symptomatic and asymptomatic events that were documented,
      including those that met predefined immediate physician notification criteria and
      the time to first notification event. The groups were identical in age and
      symptoms that necessitated monitoring; fewer women had HM. Information on the
      type of underlying structural heart disease, if present, and medications taken,
      if any, was not available to us in this database. The AT-MLR approach provided a
      higher yield of diagnostic events (e.g., 37, 108, and 216 total patients who had
      events; 37, 212, and 524 total events; and 6.2%, 17%, and 36% with a diagnostic
      yield for HM, MLR, and AT-MLR, respectively) and an earlier diagnosis. AT-MLR was
      also the most effective technique for capturing asymptomatic significant events,
      such as atrial fibrillation (52 with AT-MLR vs 1 for standard MLR). AT-MLR
      detected more than half as many asymptomatic episodes of atrial fibrillation (n =
      52) as the total number of symptomatic episodes detected by patient activated
      recording (n = 94), thus confirming the common presence of asymptomatic atrial
      fibrillation. AT-MLR provided electrocardiographic documentation of
      tachyarrhythmias (n = 392) more often than MLR (n = 47) or HM (n = 44) and
      bradyarrhythmias/pauses/atrioventricular block (n = 38) more often than MLR (n =
      13) or HM (n = 18). Thus, MLR and AT-MLR provide a diagnosis more often than does
      HM, thus confirming the benefit of prolonged monitoring. Further, the higher
      yield of AT-MLR versus MLR demonstrates the significantly enhanced benefit of
      autotriggered programmable recording.

PMID- 15842971
TI  - Long-term effects of stress reduction on mortality in persons > or = 55 years of
      age with systemic hypertension.
AB  - Psychosocial stress contributes to high blood pressure and subsequent
      cardiovascular morbidity and mortality. Previous controlled studies have
      associated decreasing stress with the Transcendental Meditation (TM) program with
      lower blood pressure. The objective of the present study was to evaluate, over
      the long term, all-cause and cause-specific mortality in older subjects who had
      high blood pressure and who participated in randomized controlled trials that
      included the TM program and other behavioral stress-decreasing interventions.
      Patient data were pooled from 2 published randomized controlled trials that
      compared TM, other behavioral interventions, and usual therapy for high blood
      pressure. There were 202 subjects, including 77 whites (mean age 81 years) and
      125 African-American (mean age 66 years) men and women. In these studies, average
      baseline blood pressure was in the prehypertensive or stage I hypertension range.
      Follow-up of vital status and cause of death over a maximum of 18.8 years was
      determined from the National Death Index. Survival analysis was used to compare
      intervention groups on mortality rates after adjusting for study location. Mean
      follow-up was 7.6 +/- 3.5 years. Compared with combined controls, the TM group
      showed a 23% decrease in the primary outcome of all-cause mortality after maximum
      follow-up (relative risk 0.77, p = 0.039). Secondary analyses showed a 30%
      decrease in the rate of cardiovascular mortality (relative risk 0.70, p = 0.045)
      and a 49% decrease in the rate of mortality due to cancer (relative risk 0.49, p
      = 0.16) in the TM group compared with combined controls. These results suggest
      that a specific stress-decreasing approach used in the prevention and control of
      high blood pressure, such as the TM program, may contribute to decreased
      mortality from all causes and cardiovascular disease in older subjects who have
      systemic hypertension.

PMID- 15842972
TI  - Matrix metalloproteinases and their inhibitors in malignant and autoreactive
      pericardial effusion.
AB  - Matrix metalloproteinases (MMPs) are proteolytic enzymes essentially involved in
      tissue remodeling and tumor invasion, and their activity is counterbalanced by
      endogenous antagonists, the tissue inhibitors of matrix proteinases (TIMPs).
      Recent reports have suggested a potential role of MMPs in the evolution of
      pericardial effusion (PE). In this study, we determined the levels of MMP-2 and
      MMP-9 and their inhibitors TIMP-1 and TIMP-2 in 19 patients who had malignant PE
      that was confirmed by histology or cytology and 30 patients who had nonmalignant,
      autoreactive PE compared with pericardial fluid of 19 patients who had preserved
      left ventricular function and who underwent aortocoronary bypass surgery for
      control. Samples were assayed by zymography, immunoblotting, and quantitative
      enzyme-linked immunosorbent assay. We found significantly higher MMP-2 levels in
      malignant PE than in pericardial fluid (2,906 +/- 348 vs 1,493 +/- 114 ng/ml, p =
      0.0005) or autoreactive PE (2,079 +/- 269 ng/ml, p = 0.01). No significant
      differences in MMP-9 levels were found between malignant PE and autoreactive PE
      (83 +/- 28.6 vs 106 +/- 30.4 ng/ml, p = 0.22), whereas MMP-9 was below the
      detection limit in pericardial fluid. No differences in TIMP-1 levels were found
      across the different study groups, whereas compared with pericardial fluid, TIMP
      2 levels were significantly lower in autoreactive PE (113 +/- 18.9 vs 187 +/-
      12.2 ng/ml, p = 0.002). In addition, there was a trend to lower TIMP-2 levels in
      malignant PE (137 +/- 27.1 ng/ml, p = 0.07). The present findings indicate that
      proteolytic enzymes and their inhibitors are involved in the pathogenesis of PE,
      with an expression pattern that depends on etiology. The involvement of MMP-2 in
      the pathogenesis of malignant PE may indicate a potential role of MMP inhibitors
      in the control of malignant PE.

PMID- 15842973
TI  - Prevalence of T-wave inversion beyond V1 in young normal individuals and
      usefulness for the diagnosis of arrhythmogenic right ventricular
      cardiomyopathy/dysplasia.
AB  - T-wave inversion in precordial leads V1 to V3 is present in <3% of apparently
      healthy subjects who are 19 to 45 years of age but is present in 87% of patients
      who have arrhythmogenic right ventricular cardiomyopathy/dysplasia. T-wave
      inversion in lead V2 or V3 in a young or middle-aged patients who have no
      apparent heart disease but do have ventricular arrhythmias of left bundle branch
      morphology should raise the suspicion of arrhythmogenic right ventricular
      cardiomyopathy/dysplasia.

PMID- 15842974
TI  - Comparison of all-cause mortality in women with known or suspected coronary
      artery disease referred for dobutamine stress echocardiography with normal versus
      abnormal test results.
AB  - The presence of myocardial ischemia during dobutamine stress echocardiography is
      independently associated with an increased risk of all-cause mortality in women
      after adjustment for clinical data. This association is observed in patients who
      have proved coronary artery disease and in patients who have no history of
      coronary artery disease.

PMID- 15842975
TI  - Ability for visualization, reasons for nonassessable image, and diagnostic
      accuracy of 16-slice multidetector row helical computed tomography for the
      assessment of the entire coronary arteries.
AB  - It was demonstrated that 16-slice multidetector row helical computed tomography
      may permit more accurate assessment of entire coronary arteries, with a low rate
      of arteries unable to be evaluated. The detection of coronary artery stenoses
      with this modality was applicable to assessable segments.

PMID- 15842976
TI  - Effectiveness of high-intensity interval training for the rehabilitation of
      patients with coronary artery disease.
AB  - We found that interval training provides an effective means to improve the
      cardiovascular fitness and health status of highly functional patients with
      coronary artery disease. We also revealed that interval training improves
      anaerobic tolerance to a greater extent than the traditional exercise training
      model without increasing the risk to the patient. This research supports the
      implementation of interval training for highly functional patients with coronary
      artery disease.

PMID- 15842977
TI  - Effectiveness of inhibition of cholesteryl ester transfer protein by JTT-705 in
      combination with pravastatin in type II dyslipidemia.
AB  - The inhibition of cholesteryl ester transfer protein (CETP) has recently been
      shown to effectively increase high-density lipoprotein (HDL) cholesterol. This
      study examined the use of the CETP inhibitor JTT-705 combined with pravastatin.
      In a randomized, double-blind, placebo-controlled trial, 155 patients with type
      II dyslipidemia using pravastatin 40 mg were treated with placebo or JTT-705 300
      or 600 mg. Four weeks of treatment with JTT-705 600 mg led to a 30% decrease in
      CETP activity (p <0.001), a 28% increase in HDL cholesterol (p <0.001), and a 5%
      decrease in low-density lipoprotein cholesterol (p <0.03). Combination therapy
      using JTT-705 and pravastatin effectively increases HDL cholesterol levels and is
      safe and well tolerated up to 4 weeks of administration.

PMID- 15842978
TI  - Effect of chronic total coronary occlusion on treatment strategy.
AB  - In a registry analysis of 8,004 consecutive patients presenting for diagnostic
      catheterization at a single institution from 1990 to 2000, chronic total
      occlusion (CTO) was found in 52% of patients with significant (> or = 70%
      diameter stenosis) coronary artery disease. Peripheral vascular disease was the
      strongest clinical predictor of the presence of a CTO. In a multivariate
      analysis, CTO was the strongest predictor against the selection of percutaneous
      coronary intervention (PCI) as a treatment strategy, indicating that efforts to
      improve the success rate of PCI in CTO may have a significant impact on
      management of coronary disease.

PMID- 15842979
TI  - Outcomes following elective percutaneous coronary intervention without on-site
      surgical backup in a community hospital.
AB  - Despite guidelines to the contrary, limited numbers of elective percutaneous
      coronary intervention (PCI) procedures without on-site surgical backup are being
      performed, particularly in Europe and Canada. In the United States, many
      hospitals are considering establishing on-site surgical programs, in part to
      facilitate PCI. At a hospital with only off-site surgical backup, 562 elective
      PCI procedures were performed on 489 consecutive patients. Of these, 551 (98.0%)
      were successfully completed without major in-hospital complications; 5 patients
      (1.0%) had in-hospital complications, and 4 (0.8%) were urgently transferred. It
      is concluded that elective PCI with off-site surgical backup is feasible and safe
      for selected patients under specific conditions.

PMID- 15842980
TI  - Follow-up of coronary artery bypass graft patency by multislice computed
      tomography.
AB  - Fifty-two consecutive asymptomatic patients with a total of 166 bypass grafts
      were investigated by 16-slice computed tomography (CT) 15 +/- 5 days before
      invasive coronary angiography. Overall, 165 grafts (99.4%) were assessable with
      multislice CT (MSCT). Coronary angiography showed that 111 grafts (67%) were
      patent and 54 (33%) were occluded. Of the patent grafts, 22 had high-grade
      stenoses. MSCT correctly classified 111 grafts as patent and 54 as occluded. Of
      the patent grafts, 16-slice CT correctly detected 21 bypass stenoses (95%). These
      results yielded 100% sensitivity and specificity of 16-slice CT for detecting
      bypass grafts occlusion and 96% sensitivity and 100% specificity for detecting
      high-grade stenoses in patent grafts.

PMID- 15842981
TI  - Do statins increase the risk of idiopathic polyneuropathy?
AB  - A recent European case-control study suggested that statins increase the risk for
      polyneuropathy, a rare but serious neurologic condition. This risk was assessed
      in 272 patients with idiopathic polyneuropathy and 1,360 matched controls in the
      Intermountain Health Care electronic database. It was found that statin use
      before diagnosis was not significantly greater in patients than controls (odds
      ratio 1.30, 95% confidence interval 0.3 to 2.1, p = 0.27), nor were doses
      different between patients and controls.

PMID- 15842982
TI  - Relation of echocardiographic wall motion score index and response to dobutamine
      stress to defibrillation threshold at the time of implantation of a cardiac
      defibrillator.
AB  - Predictors of defibrillation threshold (DFT) at implantation remain poorly
      defined. It was hypothesized that a greater wall motion score index (WMSI) at
      rest on echocardiography and an ischemic or biphasic response on dobutamine
      stress echocardiography (DSE) would predict a greater DFT. Consecutive patients
      who underwent implantable cardiac-defibrillator implantation underwent
      echocardiography and DSE. DFT at implantation was assessed using the step-down
      method. Thirteen men aged 68 +/- 10 years with left ventricular ejection
      fractions of 28 +/- 10% participated in the study. DFTs ranged from 5 to 25 J
      (mean 14 +/- 8). A WMSI at rest of > or = 2.5 had a 71% positive predictive value
      and an 83% negative predictive value for a DFT > or = 15 J. An ischemic or
      biphasic response during DSE did not predict a greater DFT at implantation.

PMID- 15842983
TI  - Effect of syncope-related traumatic injuries on the diagnostic evaluation and
      syncope recurrence of patients with syncope and apparently normal hearts.
AB  - The aims of this study were to assess the frequency of traumatic injuries in
      patients with syncope and apparently normal hearts and their influence on the
      diagnostic evaluation and recurrence of syncope. Patients presenting with syncope
      before head-up tilt testing frequently had a history of syncope-related injuries.
      Syncope-related injuries seemed to be random: they was not related to patients'
      histories, including the number of previous syncopal attacks, and they had no
      predictive value for the outcome of head-up tilt testing or for the recurrence of
      syncope during 1-year follow-up.

PMID- 15842984
TI  - Monitoring of physical activity and heart rate variability in patients with
      chronic heart failure using cardiac resynchronization devices.
AB  - Cardiac resynchronization therapy (CRT) devices not only deliver effective
      treatment but may also serve as valuable diagnostic tools in heart failure
      management. In the present study, the minutes of daily physical activity and
      heart rate variability, measured by sensors incorporated into such a device,
      reflected the effects of CRT and were related to New York Heart Association
      functional class.

PMID- 15842985
TI  - Echocardiographic examination of atrioventricular and interventricular delay
      optimization in cardiac resynchronization therapy.
AB  - In 21 patients implanted with a biventricular pacing device with programmable
      interventricular delay (VVd), the myocardial performance index (MPI) was
      evaluated during spontaneous sinus rhythm, simultaneous biventricular pacing, and
      sequential biventricular pacing at different VVds and atrioventricular delays
      (AVds). The AVd-VVd combination associated with the minimum MPI defined patient
      tailored biventricular pacing. Simultaneous biventricular pacing significantly
      improved MPI compared with spontaneous sinus rhythm. An additional improvement
      was obtained by tailored biventricular pacing. The optimal AVds were
      significantly shorter during right ventricular preactivation than during left
      ventricular preactivation.

PMID- 15842986
TI  - Effect of cardiac resynchronization therapy on inducibility of ventricular
      tachyarrhythmias in cardiac arrest survivors with either ischemic or idiopathic
      dilated cardiomyopathy.
AB  - We evaluated whether long-term cardiac resynchronization therapy affects the
      inducibility of ventricular tachyarrhythmias in relation to reverse remodeling in
      cardiac arrest survivors with either ischemic or idiopathic dilated
      cardiomyopathy. Clinical, electrophysiologic, and echocardiographic data of 18
      patients were obtained before and after 6 months of cardiac resynchronization.

PMID- 15842987
TI  - Long-term effects of carvedilol or metoprolol on left ventricular function in
      ischemic and nonischemic cardiomyopathy.
AB  - Data regarding the effects of beta blockers on left ventricular (LV) function
      after 12 months are scarce in ischemic and nonischemic cardiomyopathy.
      Echocardiograms of 72 patients with ischemic and nonischemic cardiomyopathy, who
      were free of clinical events susceptible to alter LV function while receiving
      carvedilol or metoprolol for at least 24 months, were prospectively reanalyzed.
      Twelve months after beta-blocker initiation, LV ejection fraction (EF) increased
      by > or = 5% in 75% of patients, whereas EF failed to increase by 5% or decreased
      in the remaining 25%. Over the subsequent 32 months, LVEF increased further in
      patients who had experienced an initial EF increase by > or = 5%, whereas EF
      tended to further decrease in patients who had experienced an initial EF increase
      of <5% or a decrease. Thus, the benefits of carvedilol or metoprolol on LV
      function are long lasting in patients with ischemic or nonischemic cardiomyopathy
      who are free of events susceptible to alter LV function while receiving beta
      blockade.

PMID- 15842988
TI  - Prognostic impact of diabetes mellitus in patients with acute decompensated heart
      failure.
AB  - The presence of diabetes mellitus (DM) adversely affects the natural history of
      heart failure (HF), but its prognostic significance is unknown in acute
      decompensated HF. Of the 498 patients enrolled with decompensated HF requiring
      intravenous vasoactive therapy, 236 (47.4%) had a previous diagnosis of DM. After
      6 months, 113 patients (22.7%) had died. A Cox proportional-hazards model showed
      a significant association between DM and worse survival after hospital discharge.
      DM is common among patients admitted with decompensated HF, and diabetes-related
      biologic differences contribute to the progression of HF.

PMID- 15842989
TI  - Effect of a seated exercise program to improve physical function and health
      status in frail patients > or = 70 years of age with heart failure.
AB  - Eighty-two patients aged > or = 70 years with heart failure were randomized to a
      gentle, seated exercise program or to usual care. Six-minute walk distance and
      quality of life did not change between groups, but daily activity as measured by
      accelerometry increased in the exercise group relative to the control group.

PMID- 15842990
TI  - Usefulness of enalapril versus propranolol or atenolol for prevention of aortic
      dilation in patients with the Marfan syndrome.
AB  - Despite variable clinical results, beta blockers have become the primary therapy
      for prevention of aortic dilation in patients with the Marfan syndrome. This
      study examines the use of the angiotensin-converting enzyme inhibitor enalapril
      for treatment of these patients. We sought to examine the effects of enalapril
      versus beta-blocker therapy in patients with the Marfan syndrome and noted
      improved aortic distensibility (3.0 +/- 0.3 vs 1.9 +/- 0.4 cm2 dynes(-1); p
      <0.02) and a reduced aortic stiffness index (8.0 +/- 2.9 vs 18.4 +/- 3.8; p
      <0.05) in patients receiving enalapril compared with those receiving beta
      blockers. These favorable hemodynamic changes were associated with a smaller
      increase in aortic root diameter (0.1 +/- 1.0 vs 5.8 +/- 5.2 mm) and fewer
      clinical end points during follow-up.

PMID- 15842991
TI  - Mechanism of spaceflight-induced changes in left ventricular mass.
AB  - Decrements in left ventricular (LV) mass observed after microgravity exposure
      have been previously postulated to be a central component of spaceflight-induced
      cardiovascular deconditioning. In this study, echocardiographic measurements of
      LV mass in astronauts demonstrated a comparative 9.1% reduction in postflight LV
      mass that returned to preflight values by the third day of recovery. A ground
      based study in normal subjects determined that these pre- to postflight LV mass
      changes could be reproduced by simple dehydration. Reductions in LV mass observed
      immediately after spaceflight may be secondary to simple physiologic fluid
      exchanges.

PMID- 15842992
TI  - Usefulness of contrast echocardiography for diagnosis of left ventricular
      noncompaction.
AB  - Many imaging modalities have been evaluated for the diagnosis of left ventricular
      noncompaction (LVNC). Echocardiography with color Doppler flow imaging is
      currently the diagnostic modality of choice. In this study, the usefulness of
      contrast echocardiography to diagnose LVNC was examined, and the diagnostic
      criteria were evaluated.

PMID- 15842993
TI  - Synthesis and membrane behavior of a new class of unnatural phospholipid analogs
      useful as phospholipase A2 degradable liposomal drug carriers.
AB  - A new and unnatural type of lipid analogs with the phosphocholine and
      phosphoglycerol head groups linked to the C-2 position of the glycerol moiety
      have been synthesized and the thermodynamic lipid membrane behavior has been
      investigated using differential scanning calorimetry. From the heat capacity
      measurements, it was observed that the pre-transition was abolished most likely
      due to the central position of the head groups providing better packing
      properties in the low temperature ordered gel phase. Activity measurements of
      secretory phospholipase A2 (PLA2) on unilamellar liposomal membranes revealed
      that the unnatural phospholipids are excellent substrates for PLA2 catalyzed
      hydrolysis. This was manifested as a minimum in the PLA2 lag time in the main
      phase transition temperature regime and a high degree of lipid hydrolysis over a
      broad temperature range. The obtained results provide new information about the
      interplay between the molecular structure of phospholipids and the lipid membrane
      packing constrains that govern the pre-transition. In addition, the PLA2 activity
      measurements are useful for obtaining deeper insight into the molecular details
      of the catalytic site of PLA2. The combined results also suggest new approaches
      to rationally design liposomal drug carries that can undergo a triggered
      activation in diseased tissue by overexpressed PLA2.

PMID- 15842994
TI  - Phase transitions as a function of osmotic pressure in Saccharomyces cerevisiae
      whole cells, membrane extracts and phospholipid mixtures.
AB  - Fourier Transform Infrared spectroscopy (FTIR) was used to determine the phase
      transition temperature of whole Saccharomyces cerevisiae W303-1 A cells as a
      function of Aw in binary water-glycerol media. A phase transition occurred at 12
      degrees C in water, at 16.5 degrees C at Aw=0.75, and at 19.5 degrees C at
      Aw=0.65. The temperature ranges over which transition occurred increased with
      decreasing Aw. A total lipid extract of the plasma membranes isolated from S.
      cerevisiae cells was also studied, with a phase transition temperature determined
      at 20 degrees C in pure water and at 27 degrees C in binary water-glycerol
      solutions for both Aw levels tested. The pure phospholipids
      dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine
      (DMPE) and three binary mixtures of these phospholipids (percentage molar
      mixtures of DMPC/DMPE of 90.5/9.5, 74.8/25.2, and 39.7/60.3) were studied. For
      DMPC, there was no influence of Aw on the phase transition temperature (always 23
      degrees C). On the other hand, the phase transition temperature of DMPE increased
      with decreasing Aw for the three aqueous solutions tested (glycerol, sorbitol and
      sucrose), from 48 degrees C in water, to 64 degrees C for a solution at Aw=0.67.
      For the DMPC/DMPE mixtures, transitions were found intermediate between those of
      the two phospholipids, and a cooperative state was observed between species at
      the gel and at the fluid phases.

PMID- 15842995
TI  - Regeneration and inhibition of proton pumping activity of bacteriorhodopsin blue
      membrane by cationic amine anesthetics.
AB  - Bacteriorhodopsin (bR) is the prototype of an integral membrane protein with
      seven membrane-spanning alpha-helices and serves as a model of the G-protein
      coupled drug receptors. This study is aimed at reaching a greater understanding
      of the role of amine local anesthetic cations on the proton transport in the bR
      protein, and furthermore, the functional role of "the cation" in the proton
      pumping mechanism. The effect of the amine anesthetic cations on the proton pump
      in the bR blue membrane was compared with those by divalent (Ca2+, Mg2+ and Mn2+)
      and monovalent metal cations (Li+, Na+, K+ and Cs+), which are essential for the
      correct functioning of the proton pumping of the bR protein. The results suggest
      that the interacting site of the divalent cation to the bR membrane may differ
      from that of the monovalent metal cation. The electric current profile of the bR
      blue membrane in the presence of the amine anesthetic cations was biphasic,
      involving the generation and inhibition of the proton pumping activity in a
      concentration-dependent manner. The extent of the regeneration of the proton pump
      by the additives increased in the order of monovalent metal cation<monovalent
      amine anesthetic cation<divalent metal cation. We found that organic cations such
      as the amine anesthetics can also regenerate the proton pump in the bR protein.
      The inhibition of proton transport in the bR protein by the anesthetic cations
      was elucidated using the wild type, the E204Q and the D96N mutated bRs. The
      hydrophobic interaction of the amine anesthetics with the bR protein plays an
      important part in inhibiting the bR proton pump.

PMID- 15842996
TI  - Leukotriene and purinergic receptors are involved in the hyperpolarizing effect
      of glucagon in liver cells.
AB  - The pancreatic hormone glucagon hyperpolarizes the liver cell membrane. In the
      present study, we investigated the cellular signalling pathway of glucagon
      induced hyperpolarization of liver cells by using the conventional microelectrode
      method. The membrane potential was recorded in superficial liver cells of
      superfused mouse liver slices. In the presence of the K+ channel blockers
      tetraethylammonium (TEA, 1 mmol/l) and Ba2+ (BaCl2, 5 mmol/l) and the blocker of
      the Na+/K+ ATPase, ouabain (1 mmol/l), no glucagon-induced hyperpolarization was
      observed confirming previous findings. The hyperpolarizing effect of glucagon was
      abolished by the leukotriene B4 receptor antagonist CP 195543 (0.1 mmol/l) and
      the purinergic receptor antagonist PPADS (5 micromol/l). ATPgammaS (10
      micromol/l), a non-hydrolyzable ATP analogue, induced a hyperpolarization of the
      liver cell membrane similar to glucagon. U 73122 (1 micromol/l), a blocker of
      phospholipase C, prevented both the glucagon- and ATPgammaS-induced
      hyperpolarization. These findings suggest that glucagon affects the hepatic
      membrane potential partly by inducing the formation and release of leukotrienes
      and release of ATP acting on purinergic receptors of the liver cell membrane.

PMID- 15842997
TI  - Epithelial transport and barrier function in occludin-deficient mice.
AB  - BACKGROUND AND AIMS: This study aimed at functional characterization of the tight
      junction protein occludin using the occludin-deficient mouse model. METHODS:
      Epithelial transport and barrier functions were characterized in Ussing chambers.
      Impedance analysis revealed the ionic permeability of the epithelium (Re,
      epithelial resistance). Conductance scanning differentiated transcellular (Gc)
      and tight junctional conductance (Gtj). The pH-stat technique quantified gastric
      acid secretion. RESULTS: In occludin+/+ mice, Re was 23+/-5 Omega cm2 in jejunum,
      66+/-5 Omega cm2 in distal colon and 33+/-6 Omega cm2 in gastric corpus and was
      not altered in heterozygotic occludin+/- or homozygotic occludin-/- mice.
      Additionally, [3H]mannitol fluxes were unaltered. In the control colon, Gc and
      Gtj were 7.6+/-1.0 and 0.3+/-0.1 mS/cm2 and not different in occludin deficiency.
      Epithelial resistance after mechanical perturbation or EGTA exposition (low
      calcium switch) was not more affected in occludin-/- mice than in control.
      Barrier function was measured in the urinary bladder, a tight epithelium, and in
      the stomach. Control Rt was 5.8+/-0.8 kOmega cm2 in urinary bladder and 33+/-6
      Omega cm2 in stomach and not altered in occludin-/- mice. In gastric corpus
      mucosa, the glandular structure exhibited a complete loss of parietal cells and
      mucus cell hyperplasia, as a result of which acid secretion was virtually
      abolished in occludin-/- mice. CONCLUSION: Epithelial barrier characterization in
      occludin-deficiency points against an essential barrier function of occludin
      within the tight junction strands or to a substitutional redundancy of single
      tight junction molecules like occludin. A dramatic change in gastric morphology
      and secretory function indicates that occludin is involved in gastric epithelial
      differentiation.

PMID- 15842998
TI  - Isolation and characterization of a thylakoid membrane module showing partial
      light and dark reactions.
AB  - A functional thylakoid membrane module of photosynthesis was isolated from cell
      free extracts of Anacystis nidulans by stepwise sequential ultracentrifugation.
      The thylakoid membrane fractions sedimenting at 40,000 x g, followed by 90,000 x
      g and finally at 150,000 x g were collected. These fractions had all the
      components of electron transport chain, ATP synthase, phycobiliproteins,
      ferredoxin-NADP reductase but no ferredoxin. Five sequential enzymes of Calvin
      cycle viz phosphoriboisomerase, phosphoribulokinase, RuBP carboxylase, 3-PGA
      kinase and glyceraldehyde-3-phosphate dehydrogenase were found to be associated
      with thylakoid membranes. Among the three different thylakoid fractions, the
      150,000 x g fraction showed highest activities of these enzymes and also higher
      rate of whole chain electron transport activity on chlorophyll basis. An
      important finding was that the 150,000 x g fraction showed appreciably higher
      rate of R-5-P+ADP+Pi dependent CO2 fixation in light compared to the other two
      fractions, indicating the efficiency of this fraction in utilizing ATP for Calvin
      cycle. This thylakoid membrane fraction represents a fully functional module
      exhibiting a synchronized system of light and dark reactions of photosynthesis.
      Most of the components of this module remained together even after sucrose
      density gradient centrifugation. This is the first report on the isolation of a
      photosynthetic module involving membrane and soluble proteins.

PMID- 15842999
TI  - Actin cytoskeleton disassembly affects conductive properties of stretch-activated
      cation channels in leukaemia cells.
AB  - Mechanosensitive channels in various eucaryotic cells are thought to be
      functionally and structurally coupled to the cortical cytoskeleton. However, the
      results of electrophysiological studies are rather controversial and the
      functional impact of cytoskeleton assembly-disassembly on stretch-activated
      channel properties remains unclear. Here, the possible involvement of
      cytoskeletal elements in the regulation of stretch-activated Ca2+-permeable
      channels was studied in human leukaemia K562 cells with the use of agents that
      selectively modify the actin or tubulin system. F-actin disassembly resulted in a
      considerable reduction of the amplitude of stretch-activated currents without
      significant change in channel open probability. The effects of treatments with
      cytochalasins or latrunculin were principally similar, developed gradually and
      consisted a strong decrease of single channel conductance. Microtubule disruption
      did not affect stretch-activated channels. The data presented here are in
      principal agreement with the general conclusion that mechanosensitive channel
      functions are largely dependent on the integrity of the cortical actin
      cytoskeleton. Specifically, changes in conductive properties of the pore may
      provide an essential mechanism of channel regulation underlying functional
      modulation of membrane currents. Our results allow one to speculate that
      microfilament organization may be an important determinant in modulating
      biophysical characteristics of stretch-activated cation channels in cells of
      blood origin.

PMID- 15843000
TI  - Na,K-ATPase mutations in familial hemiplegic migraine lead to functional
      inactivation.
AB  - The Na,K-ATPase is an ion-translocating transmembrane protein that actively
      maintains the electrochemical gradients for Na+ and K+ across the plasma
      membrane. The functional protein is a heterodimer comprising a catalytic alpha
      subunit (four isoforms) and an ancillary beta-subunit (three isoforms). Mutations
      in the alpha2-subunit have recently been implicated in familial hemiplegic
      migraine type 2, but almost no thorough studies of the functional consequences of
      these mutations have been provided. We investigated the functional properties of
      the mutations L764P and W887R in the human Na,K-ATPase alpha2-subunit upon
      heterologous expression in Xenopus oocytes. No Na,K-ATPase-specific pump currents
      could be detected in cells expressing these mutants. The binding of radiolabelled
      [3H]ouabain to intact cells suggested that this could be due to a lack of plasma
      membrane expression. However, plasma membrane isolation showed that the mutated
      pumps are well expressed at the plasma membrane. 86Rb+-flux and ATPase activity
      measurements demonstrated that the mutants are inactive. Therefore, the primary
      disease-causing mechanism is loss-of-function of the Na,K-ATPase alpha2-isoform.

PMID- 15843001
TI  - Antiangiogenic photodynamic therapy (PDT) by using long-circulating liposomes
      modified with peptide specific to angiogenic vessels.
AB  - For the improvement of therapeutic efficacy in photodynamic therapy (PDT) by
      using a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), we
      previously prepared polyethylene glycol (PEG)-modified liposomes encapsulating
      BPD-MA (PEG-Lip BPD-MA). PEGylation of liposomes enhanced the accumulation of BPD
      MA in tumor tissue at 3 h after injection of it into Meth-A-sarcoma-bearing mice,
      but, unexpectedly, decreased the suitability of the drug for PDT when laser
      irradiation was performed at 3 h after the injection of the liposomal
      photosensitizer. To improve the bioavailability of PEG-Lip BPD-MA, we endowed the
      liposomes with active-targeting characteristics by using Ala-Pro-Arg-Pro-Gly
      (APRPG) pentapeptide, which had earlier been isolated as a peptide specific to
      angiogenic endothelial cells. APRPG-PEG-modified liposomal BPD-MA (APRPG-PEG-Lip
      BPD-MA) accumulated in tumor tissue similarly as PEG-Lip BPD-MA and to an approx.
      4-fold higher degree than BPD-MA delivered with non-modified liposomes at 3 h
      after the injection of the drugs into tumor-bearing mice. On the contrary, unlike
      the treatment with PEG-Lip BPD-MA, APRPG-PEG-Lip BPD-MA treatment strongly
      suppressed tumor growth after laser irradiation at 3 h after injection. Finally,
      we observed vasculature damage in the dorsal air sac angiogenesis model by APRPG
      PEG-Lip BPD-MA-mediated PDT. The present results suggest that antiangiogenic PDT
      is an efficient modality for tumor treatment and that tumor neovessel-targeted,
      long-circulating liposomes are a useful carrier for delivering photosensitizer to
      angiogenic endothelial cells.

PMID- 15843002
TI  - The thermodynamic principles of isochoric cryopreservation.
AB  - The goal of this study is to introduce the fundamental thermodynamic principles
      of isochoric (constant volume) cryopreservation for low temperature preservation
      of biological materials. Traditionally, cryopreservation is performed in an
      isobaric process (constant pressure) at 1 atm, because this is our natural
      environment and it is most convenient experimentally. More than half a century of
      studies on cryopreservation shows that the major mechanism of damage during
      isobaric cryopreservation is the increase in intracellular ionic concentration
      during freezing, which presumably causes chemical damage to the components of
      cells. Cryoprotectants as well as hyperbaric pressures have been developed as
      methods to reduce the extent of chemical damage during freezing. The theoretical
      studies in this paper show that in isochoric cryopreservation, the increase in
      solution concentration during freezing is lower at each temperature by almost an
      order of magnitude from that in isobaric cryopreservation. This suggests that
      isochoric cryopreservation could be a preferential alternative to isobaric
      cryopreservation. The technology for isochoric cryopreservation is very simple;
      freezing in a constant volume chamber. Using a simple isochoric cryopreservation
      device, we confirm the theoretical thermodynamic predictions.

PMID- 15843003
TI  - Heart valve cryopreservation: protocol for addition of dimethyl sulphoxide and
      amelioration of putative amphotericin B toxicity.
AB  - AIM: To investigate the need for stepwise addition of dimethyl sulphoxide to
      heart valves and amelioration of putative amphotericin B toxicity. METHODS: There
      were four groups: an untreated control (Group 1) and three experimental groups.
      For the latter, porcine heart valves were exposed to the antibiotic/antimycotic
      mixture used for disinfecting heart valves in the Bristol Heart Valve Bank, for
      24 h at 22 degrees C. Dimethyl sulphoxide (Me2SO, 10% v/v) was added either in
      two steps (5% then 10%) (Group 2) or in a single step. For single-step addition,
      valves were either first placed in Hanks' balanced salt solution for 10 min
      before transfer to the cryoprotectant solution (Group 3) or immersed directly in
      the 10% cryoprotectant solution (Group 4). The valve leaflets were dissected from
      the valves and frozen in 10% Me2SO in multi-well tissue culture plates at 1
      degrees C/min to -80 degrees C. After storage overnight, the valve leaflets were
      warmed at approximately 11 degrees C/min and the cryoprotectant was removed by
      single-step dilution in excess Hartmann's solution. Each leaflet was then divided
      into four pieces, which were placed in separate wells of a culture plate.
      Outgrowth of cells from the explants was monitored daily and graded according to
      the extent of cell growth. RESULTS: After freezing and thawing, only 77% of the
      explants from valves placed directly into 10% Me2SO (Group 4) showed outgrowth of
      cells after freezing compared with 89% with two-step addition of Me2SO (Group 2)
      and 95% with one-step addition after the extra rinse in Hanks' solution (Group 3)
      (chi2, p=0.001). 92% of unfrozen control explants showed outgrowth of cells
      (Group 1). Only 37% of Group 4 explants reached confluence compared with 63 and
      56%, respectively, of Groups 2 and 3 explants (chi2, p=0.007). The rates of cell
      growth in Group 2 (two-step addition of Me2SO) and Group 3 (one-step addition of
      Me2SO with additional Hanks' solution rinse) were similar and faster than the
      Group 4 (one-step addition of Me2SO without the additional Hanks' rinse).
      CONCLUSION: Single-step addition of Me2SO before freezing gave similar results to
      two-step addition provided an additional rinse in Hanks' solution was introduced
      after exposure to the antibiotic/antimycotic mixture. This suggests that
      antibiotic/antimycotic carryover may have been harmful during freezing and that
      the additional rinse in Hanks before one-step addition of Me2SO, and the 5% Me2SO
      step in the two-step protocol, merely served to reduce this carryover.

PMID- 15843004
TI  - Evaluation of DNA damage in rainbow trout (Oncorhynchus mykiss) and gilthead sea
      bream (Sparus aurata) cryopreserved sperm.
AB  - Cryopreservation causes several types of damage to spermatozoa, such as loss of
      plasma membrane integrity and functionality, loss of motility, and ATP content,
      resulting in decrease of fertility rates. This spermatozoal damage has been
      widely investigated for several marine and freshwater fish species. However, not
      much attention has been paid to the nuclear DNA. The objective of this study was
      to determine the degree to which cryopreservation induces spermatozoal DNA damage
      in two commercially cultured species, rainbow trout (Oncorhynchus mykiss) and
      gilthead sea bream (Sparus aurata), both of which could benefit from the
      development of cryopreservation strategies on a large scale. We have used the
      single-cell gel electrophoresis, commonly known as Comet assay to detect strand
      breaks in DNA. This technique was performed on fresh and cryopreserved sperm from
      both species. In rainbow trout there was a significant increase in the averages
      of fragmented DNA and Olive tail moment after cryopreservation (11.19-30.29% tail
      DNA and 13.4-53.48% Olive tail moment in fresh and cryopreserved sperm,
      respectively), as well as in the proportion of cells with a high percentage of
      DNA fragmentation. For gilthead sea bream there were no significant differences
      in the percentage of tail DNA between the control samples and sperm diluted 1:6
      and cryopreserved (28.23 and 31.3% DNA(t), respectively). However, an increase in
      the sperm dilution rate produced an increase in the percentage of DNA
      fragmentation (41.4%). Our study demonstrates that cryopreservation can induce
      DNA damage in these species, and that this fact should be taken into account in
      the evaluation of freezing/thawing protocols, especially when sperm
      cryopreservation will be used for gene bank purposes.

PMID- 15843005
TI  - Cryopreservation of human endothelial cells for vascular tissue engineering.
AB  - To investigate the influence of cryopreservation on endothelial cell growth,
      morphology, and function human umbilical vein endothelial cells (HUVECs) were
      frozen following a standard protocol. Cell suspensions were exposed to 10%
      dimethyl sulfoxide in a high-potassium solution, cooled to -80 degrees C at 1
      degrees C/min and stored in liquid nitrogen for 7-36 days. Samples were thawed in
      a 37 degrees C water bath and the cryoprotectant was removed by serial dilution.
      The growth of cell suspensions was assayed by culturing 7300 cells/cm2 for 3-5
      days in order to determine the cell multiplication factor. Fresh and
      cryopreserved/thawed cells were analyzed for their growth, and their anti
      inflammatory and anti-coagulant function by using cellular ELISA.
      Cryopreservation resulted in a retrieval of 66 +/- 5% and a viability of 79 +/-
      3%. Cryopreserved/thawed and fresh cells showed identical doubling times and
      identical cell counts in the confluent monolayers. However, the lag phase of
      thawed HUVECs was approximately 36 h longer, resulting in significant differences
      in the cell multiplication factor at 3 and 5 days after seeding. After expansion
      to a sufficient cell count the lag phases were identical. Fresh and
      cryopreserved/thawed cells showed comparable anti-inflammatory and anti-coagulant
      activity, as judged by the basal and TNF-induced VCAM-1, ICAM-1, E-selectin, and
      thrombomodulin expression. Cryopreserved/thawed and recultivated endothelial
      cells are suitable for endothelialization of autologous allograft veins. Such
      tissue-engineered grafts will offer the necessary clinical safety for those
      patients who lack autologous material.

PMID- 15843006
TI  - In vitro model systems for evaluation of smooth muscle cell response to
      cryoplasty.
AB  - Restenosis is a major health care problem, with approximately 40% of
      angioplasties resulting in restenosis. Mechanisms related to elastic recoil, cell
      proliferation, and extracellular matrix (ECM) synthesis are implicated. In vivo
      studies have demonstrated the potential for cryotherapy to combat the process of
      restenosis, but the mechanisms whereby freezing and/or cooling can reduce or
      eliminate smooth muscle cell (SMC) proliferation and ECM synthesis are not well
      known. While in vivo testing is ultimately necessary, in vitro models can provide
      important information on thermal parameters and mechanisms of injury. However, it
      is important to carefully choose the model system for in vitro work on cryoinjury
      characterization to adequately reflect the clinical situation. In this study, we
      examined the differences in response to cryoinjury by SMCs from different species
      (rat, pig, and human) and in different cellular environments (suspension vs.
      tissue equivalent). Tissue equivalents, composed of cells embedded in collagen or
      fibrin gel, provide a 3-D tissue-like environment, while allowing for controlled
      composition. As reported here, all SMCs showed similar trends, but rat cells
      appeared less sensitive to cooling at faster cooling rates in suspension, while
      human SMCs were less sensitive to temperatures just above freezing when embedded
      in collagen. In addition, the SMCs were less sensitive in suspension than they
      were in collagen. Cells in suspension exhibited 70% viability at -11 degrees C,
      whereas cells in the tissue equivalent model showed only 30% survival. Future
      studies will aim to more adequately represent the conditions in restenosis by
      providing inflammatory and proliferative cues to the cells.

PMID- 15843007
TI  - Selective freezing of target biological tissues after injection of solutions with
      specific thermal properties.
AB  - Cryosurgery is a minimally invasive surgical technique that employs the
      destructive effect of freezing to eradicate undesirable tissues. This paper
      proposes a flexible method to control the size and shape of the iceball by
      injecting solutions with specific thermal properties into the target tissues, to
      enhance freezing damage to the diseased tissues while preserving the normal
      tissues from injury. The cryosurgical procedure was performed using a minimally
      invasive cryoprobe cooled by liquid nitrogen (LN2) to obtain deep regional
      freezing. Several needle thermocouples were applied simultaneously to record the
      transient temperature to detect the freezing effect on the tissues. Simulation
      experiments on biological tissue (fresh pork) were performed in vitro and four
      different liquids were injected into the test materials; these were distilled
      water, an aqueous suspension of aluminum nanoparticles in water, ethanol, and a
      10% solution of the cryoprotective agent dimethyl sulfoxide (Me2SO). The
      experimental results demonstrate that the localized injection of an appropriate
      solution could enhance the tumor-killing effect without altering the freezing
      conditions. The study also suggests the potential value of combining cryosurgery
      with other therapeutic methods, such as electrical, chemical, and thermal
      treatments, to develop new clinical modalities in the near future.

PMID- 15843008
TI  - Numerical simulation of selective freezing of target biological tissues following
      injection of solutions with specific thermal properties.
AB  - Recently, we proposed a method for controlling the extent of freezing during
      cryosurgery by percutaneously injecting some solutions with particular thermal
      properties into the target tissues. In order to better understand the mechanism
      of the enhancement of freezing by these injections, a new numerical algorithm was
      developed to simulate the corresponding heat transfer process that is involved.
      The three-dimensional phase change processes in biological tissues subjected to
      cryoprobe freezing, with or without injection, were compared numerically. Two
      specific cases were investigated to illustrate the selective freezing method: the
      injection of solutions with high thermal conductivity; the injection of solutions
      with low latent heat. It was found that the localized injection of such solutions
      could significantly enhance the freezing effect and decrease the lowest
      temperature in the target tissues. The result also suggests that the injection of
      these solutions may be a feasible and flexible way to control the size of the ice
      ball and its direction of growth during cryosurgery, which will help to optimize
      the treatment process.

PMID- 15843009
TI  - Osmotic tolerance of mouse spermatozoa from various genetic backgrounds: acrosome
      integrity, membrane integrity, and maintenance of motility.
AB  - All cells have an intrinsic biophysical property related to their ability to
      undergo osmotically driven volume changes. This project is of fundamental
      importance to our understanding of the basic cryobiology of mouse spermatozoa.
      The objectives of this study were to determine the osmotic tolerance limits for
      (1) motility, (2) acrosome integrity, and (3) membrane integrity of mouse
      spermatozoa from multiple genetic backgrounds including: C57BL/6, BALB/c, FVB,
      C3H, 129/SVS2 hsd B6C3F1, CB6F1, and ICR. The maintenance of acrosomal and plasma
      membrane integrity was not affected by genetic background (p=0.13), however,
      there was an interaction between genetic background and osmolality. In addition,
      acrosome and plasma membrane integrity was highly correlated within each strain
      (p<0.01). In contrast to acrosome and plasma membrane integrity, the motility of
      spermatozoa from different genetic backgrounds fell sharply on both sides of
      isosmolality, both with and without return to isosmotic conditions. Exposure to
      hyposmotic conditions caused morphological changes in the spermatozoa, which
      inhibited motility. However, this morphological change was not reversible in all
      cases when returned to isosmotic conditions. The ability to maintain motility in
      an anisosmotic media was affected by genetic background, osmolality as well as
      the interaction between genetic background and osmolality (p<0.05). In
      conclusion, mice with different genetic backgrounds appear to have similar
      tolerance to osmotic changes in terms of sperm acrosome and plasma membrane
      integrity; however, the ability to maintain motility differs between genetic
      backgrounds.

PMID- 15843010
TI  - Non-transmission of bacterial and viral microbes to embryos and semen stored in
      the vapour phase of liquid nitrogen in dry shippers.
AB  - Cryopreservation and storage of germplasm is an important factor in the
      prevention of disease transmission by embryo transfer and artificial
      insemination. Here we report the results of an investigation on transmission of
      selected bacterial and viral pathogens by the vapour phase of liquid nitrogen
      (VPLN) to embryos and semen in dewars designed for short-term storage and
      transportation of biological specimens. In this study transmission of Pseudomonas
      aeruginosa, Escherichia coli, Staphylococcus aureus, BVDV, and BHV-1 was examined
      from: (1) contaminated dry shippers to germplasm; (2) between contaminated and
      non-contaminated cryopreserved germplasm; and (3) between stock culture of
      pathogenic agents and germplasm. Contaminated and non-contaminated samples of
      embryos and semen were stored in proximity in the vapour phase LN in open
      containers for 7 days prior to testing for the presence of microbes. The results
      showed that there was no cross-contamination from either the contaminated dewars
      to germplasm or between contaminated and non-contaminated samples of embryos and
      semen during 7 days storage under LN vapours. The outcome of our investigation
      indicates that VPLN is a safe means for short-term storage of embryos and semen
      in dry shipper dewars commonly used for transportation of bovine germplasm.

PMID- 15843011
TI  - Osteoprogenitor viability in cell populations isolated from rat femora is not
      affected by 24 h storage at 4 degrees C.
AB  - This study was initiated to determine whether partially dissected bones of rats
      could be refrigerated for 24 h in saline without losing viability of progenitor
      cells, specifically osteoprogenitors. This is directly applicable to studies
      involving bone tissue requiring overnight shipment, for example, studies
      involving space flown animals, grafting experiments, or transplantation. We
      evaluated cell populations isolated from the proximal femur of 6-week-old male
      Fisher 344 rats. Explants from the left femur were prepared and placed into
      culture immediately following dissection, while the right femur was cleaned,
      fragmented, and stored in saline at 4 degrees C for 24 h, after which explant
      cultures were initiated. After 11 days of explant culture, cells were collected
      from outgrowths, counted, and plated to initiate experiments. Plated cells were
      grown for either 15 or 21 days. To determine if storage affected the total number
      of colony forming progenitors, alkaline phosphatase positive colonies, or the
      number of osteoprogenitors, were counted. There was no significant difference in
      any of the types of colony forming units examined between cell populations
      derived from freshly prepared samples or those stored for 24 h, indicating that
      storage at 4 degrees C of bone tissue for 24 h in saline does not affect the
      osteogenic potential or the number of osteoprogenitors of the cell populations
      isolated.

PMID- 15843012
TI  - Extrusion and removal of lipid from the cytoplasm of porcine oocytes at the
      germinal vesicle stage: centrifugation under hypertonic conditions influences
      vitrification.
AB  - In the present study, we examined a novel lipid removal method, centrifugation in
      solutions made hypertonic by adding 0.27 M sugar. This allowed the lipid to be
      extruded and removed without the loss of active mitochondria or extra cytoplasm.
      The type of sugar influenced the proportion of oocytes that could be stratified
      by centrifugation. Glucose induced the highest extrusion rate of lipid droplets.
      After vitrification the rates of survival, germinal vesicle breakdown and
      metaphase II were 30, 26, and 7%, respectively, for lipid-removed GV oocytes;
      this was significantly higher (P<0.05) than for corresponding vitrified lipid
      intact oocytes (2, 0, and 0%, respectively). These results indicated that this
      method is useful to remove whole lipid droplets without losing mitochondria and
      improves cryotolerance of porcine GV oocytes.

PMID- 15843013
TI  - Alu retrotransposition-mediated deletion.
AB  - Alu repeats contribute to genomic instability in primates via insertional and
      recombinational mutagenesis. Here, we report an analysis of Alu element-induced
      genomic instability through a novel mechanism termed retrotransposition-mediated
      deletion, and assess its impact on the integrity of primate genomes. For human
      and chimpanzee genomes, we find evidence of 33 retrotransposition-mediated
      deletion events that have eliminated approximately 9000 nucleotides of genomic
      DNA. Our data suggest that, during the course of primate evolution, Alu
      retrotransposition may have contributed to over 3000 deletion events, eliminating
      approximately 900 kb of DNA in the process. Potential mechanisms for the creation
      of Alu retrotransposition-mediated deletions include L1 endonuclease-dependent
      retrotransposition, L1 endonuclease-independent retrotransposition, internal
      priming on DNA breaks, and promiscuous target primed reverse transcription. A
      comprehensive analysis of the collateral effects by Alu mobilization on all
      primate genomes will require sequenced genomes from representatives of the entire
      order.

PMID- 15843014
TI  - Discrimination between defects in elongation fidelity and termination efficiency
      provides mechanistic insights into translational readthrough.
AB  - The suppression of stop codons (termed translational readthrough) can be caused
      by a decreased accuracy of translation elongation or a reduced efficiency of
      translation termination. In previous studies, the inability to determine the
      extent to which each of these distinct processes contributes to a readthrough
      phenotype has limited our ability to evaluate how defects in the translational
      machinery influence the overall termination process. Here, we describe the
      combined use of misincorporation and readthrough reporter systems to determine
      which of these mechanisms contributes to translational readthrough in
      Saccharomyces cerevisiae. The misincorporation reporter system was generated by
      introducing a series of near-cognate mutations into functionally important
      residues in the firefly luciferase gene. These constructs allowed us to monitor
      the incidence of elongation errors by monitoring the level of firefly luciferase
      activity from a mutant allele inactivated by a single missense mutation. In this
      system, an increase in luciferase activity should reflect an increased level of
      misincorporation of the wild-type amino acid that provides an estimate of the
      overall fidelity of translation elongation. Surprisingly, we found that growth in
      the presence of paromomycin stimulated luciferase activity for only a small
      subset of the mutant proteins examined. This suggests that the ability of this
      aminoglycoside to induce elongation errors is limited to a subset of near-cognate
      mismatches. We also found that a similar bias in near-cognate misreading could be
      induced by the expression of a mutant form of ribosomal protein (r-protein) S9B
      or by depletion of r-protein L12. We used this misincorporation reporter in
      conjunction with a readthrough reporter system to show that alterations at
      different regions of the ribosome influence elongation fidelity and termination
      efficiency to different extents.

PMID- 15843015
TI  - Genetic and molecular analysis of GogB, a phage-encoded type III-secreted
      substrate in Salmonella enterica serovar typhimurium with autonomous expression
      from its associated phage.
AB  - Salmonella enterica serovar Typhimurium is lysogenized by several temperate
      bacteriophages that encode lysogenic conversion genes, which can act as virulence
      factors during infection and contribute to the genetic diversity and pathogenic
      potential of the lysogen. We have investigated the temperate bacteriophage called
      Gifsy-1 in S.enterica serovar Typhimurium and show here that the product of the
      gogB gene encoded within this phage shares similarity with proteins from other
      Gram-negative pathogens. The amino-terminal portion of GogB shares similarity
      with leucine-rich repeat-containing virulence-associated proteins from other Gram
      negative pathogens, whereas the carboxyl-terminal portion of GogB shares
      similarity with uncharacterized proteins in other pathogens. We show that GogB is
      secreted by both type III secretion systems encoded in Salmonella Pathogenicity
      Island-1 (SPI-1) and SPI-2 but translocation into host cells is a SPI-2-mediated
      process. Once translocated, GogB localizes to the cytoplasm of infected host
      cells. The genetic regulation of gogB in Salmonella is influenced by the
      transcriptional activator, SsrB, under SPI-2-inducing conditions, but the modular
      nature of the gogB gene allows for autonomous expression and type III secretion
      following horizontal gene transfer into a heterologous pathogen. These data
      define the first autonomously expressed lysogenic conversion gene within Gifsy-1
      that acts as a modular and promiscuous type III-secreted substrate of the
      infection process.

PMID- 15843016
TI  - Molecular genetics of bacteriophage P22 scaffolding protein's functional domains.
AB  - The assembly intermediates of the Salmonella bacteriophage P22 are well defined
      but the molecular interactions between the subunits that participate in its
      assembly are not. The first stable intermediate in the assembly of the P22 virion
      is the procapsid, a preformed protein shell into which the viral genome is
      packaged. The procapsid consists of an icosahedrally symmetric shell of 415
      molecules of coat protein, a dodecameric ring of portal protein at one of the
      icosahedral vertices through which the DNA enters, and approximately 250
      molecules of scaffolding protein in the interior. Scaffolding protein is required
      for assembly of the procapsid but is not present in the mature virion. In order
      to define regions of scaffolding protein that contribute to the different aspects
      of its function, truncation mutants of the scaffolding protein were expressed
      during infection with scaffolding deficient phage P22, and the products of
      assembly were analyzed. Scaffolding protein amino acids 1-20 are not essential,
      since a mutant missing them is able to fully complement scaffolding deficient
      phage. Mutants lacking 57 N-terminal amino acids support the assembly of DNA
      containing virion-like particles; however, these particles have at least three
      differences from wild-type virions: (i) a less than normal complement of the gene
      16 protein, which is required for DNA injection from the virion, (ii) a fraction
      of the truncated scaffolding protein was retained within the virions, and (iii)
      the encapsidated DNA molecule is shorter than the wild-type genome. Procapsids
      assembled in the presence of a scaffolding protein mutant consisting of only the
      C-terminal 75 amino acids contained the portal protein, but procapsids assembled
      with the C-terminal 66 did not, suggesting portal recruitment function for the
      region about 75 amino acids from the C terminus. Finally, scaffolding protein
      amino acids 280 through 294 constitute its minimal coat protein binding site.

PMID- 15843017
TI  - The X-ray structure of the type II secretion system complex formed by the N
      terminal domain of EpsE and the cytoplasmic domain of EpsL of Vibrio cholerae.
AB  - Gram-negative bacteria use type II secretion systems for the transport of
      virulence factors and hydrolytic enzymes through the outer membrane. These
      sophisticated multi-protein complexes reach from the pore in the outer membrane
      via the pseudopilins in the periplasm and a multi-protein inner-membrane sub
      complex, to an ATPase in the cytoplasm. The human pathogen Vibrio cholerae uses
      such a secretion machinery, called the Eps-system, for the export of its major
      virulence factor cholera toxin into the intestinal tract of the human host. Here,
      we describe the 2.4 A structure of the hetero-tetrameric complex of the N
      terminal domain of the ATPase EpsE and the cytoplasmic domain of the inner
      membrane protein EpsL, which constitute the major cytoplasmic components of the
      Eps-system. A stable fragment of EpsE in complex with the cytoplasmic domain of
      EpsL was identified via limited proteolysis and facilitated the crystallization
      of the complex. This first structure of a complex between two different proteins
      of the type II secretion system reveals that the N-terminal domain of EpsE and
      the cytoplasmic domain of EpsL form a hetero-tetramer, in which EpsL is the
      central dimer and EpsE binds on the periphery. The dimer of EpsL in this complex
      is very similar to the dimer seen in the crystal structure of the native
      cytoplasmic domain of EpsL, suggesting a possible physiological relevance despite
      a relatively small 675 A2 buried solvent accessible surface. The N-terminal
      domain of EpsE, which forms a compact domain with an alpha+beta-fold, places its
      helix alpha2 in a mostly hydrophobic cleft between domains II and III of EpsL
      burying 1700 A2 solvent accessible surface. This extensive interface involves
      several residues whose hydrophobic or charged nature is well conserved and is
      therefore likely to be of general importance in type II secretion systems.

PMID- 15843018
TI  - Tracing the evolution of a large protein complex in the eukaryotes,
      NADH:ubiquinone oxidoreductase (Complex I).
AB  - The increasing availability of sequenced genomes enables the reconstruction of
      the evolutionary history of large protein complexes. Here, we trace the evolution
      of NADH:ubiquinone oxidoreductase (Complex I), which has increased in size, by so
      called supernumary subunits, from 14 subunits in the bacteria to 30 in the plants
      and algae, 37 in the fungi and 46 in the mammals. Using a combination of pair
      wise and profile-based sequence comparisons at the levels of proteins and the DNA
      of the sequenced eukaryotic genomes, combined with phylogenetic analyses to
      establish orthology relationships, we were able to (1) trace the origin of six of
      the supernumerary subunits to the alpha-proteobacterial ancestor of the
      mitochondria, (2) detect previously unidentified homology relations between
      subunits from fungi and mammals, (3) detect previously unidentified subunits in
      the genomes of several species and (4) document several cases of gene
      duplications among supernumerary subunits in the eukaryotes. One of these, a
      duplication of N7BM (B17.2), is particularly interesting as it has been lost from
      genomes that have also lost Complex I proteins, making it a candidate for a
      Complex I interacting protein. A parsimonious reconstruction of eukaryotic
      Complex I evolution shows an initial increase in size that predates the
      separation of plants, fungi and metazoa, followed by a gradual adding and
      incidental losses of subunits in the various evolutionary lineages. This
      evolutionary scenario is in contrast to that for Complex I in the prokaryotes,
      for which the combination of several separate, and previously independently
      functioning modules into a single complex has been proposed.

PMID- 15843019
TI  - Local RNA target structure influences siRNA efficacy: a systematic global
      analysis.
AB  - The efficiency with which small interfering RNAs (siRNAs) down-regulate specific
      gene expression in living cells is variable and a number of sequence-governed,
      biochemical parameters of the siRNA duplex have been proposed for the design of
      an efficient siRNA. Some of these parameters have been clearly identified to
      influence the assembly of the RNA-induced silencing complex (RISC), or to favour
      the sequence preferences of the RISC endonuclease. For other parameters, it is
      difficult to ascertain whether the influence is a determinant of the siRNA per
      se, or a determinant of the target RNA, especially its local structural
      characteristics. In order to gain an insight into the effects of local target
      structure on the biological activity of siRNA, we have used large sets of siRNAs
      directed against local targets of the mRNAs of ICAM-1 and survivin. Target
      structures were classified as accessible or inaccessible using an original,
      iterative computational approach and by experimental RNase H mapping. The
      effectiveness of siRNA was characterized by measuring the IC50 values in cell
      culture and the maximal extent of target suppression. Mean IC50 values were
      tenfold lower for accessible local target sites, with respect to inaccessible
      ones. Mean maximal target suppression was improved. These data illustrate that
      local target structure does, indeed, influence the activity of siRNA. We suggest
      that local target screening can significantly improve the hit rate in the design
      of biologically active siRNAs.

PMID- 15843020
TI  - Local RNA target structure influences siRNA efficacy: systematic analysis of
      intentionally designed binding regions.
AB  - Contradictory reports in the literature have emphasised either the sequence of
      small interfering RNAs (siRNA) or the structure of their target molecules to be
      the major determinant of the efficiency of RNA interference (RNAi) approaches. In
      the present study, we analyse systematically the contributions of these
      parameters to siRNA activity by using deliberately designed mRNA constructs. The
      siRNA target sites were included in well-defined structural elements rendering
      them either highly accessible or completely involved in stable base-pairing.
      Furthermore, complementary sequence elements and various hairpins with different
      stem lengths and designs were used as target sites. Only one of the strands of
      the siRNA duplex was found to be capable of silencing via its respective target
      site, indicating that thermodynamic characteristics intrinsic to the siRNA
      strands are a basic determinant of siRNA activity. A significant obstruction of
      gene silencing by the same siRNA, however, was observed to be caused by
      structural features of the substrate RNA. Bioinformatic analysis of the mRNA
      structures suggests a direct correlation between the extent of gene-knockdown and
      the local free energy in the target region. Our findings indicate that, although
      a favourable siRNA sequence is a necessary prerequisite for efficient RNAi,
      complex target structures may limit the applicability even of carefully chosen
      siRNAs.

PMID- 15843021
TI  - Continuous assays for DNA translocation using fluorescent triplex dissociation:
      application to type I restriction endonucleases.
AB  - Fluorescent assays and accompanying kinetic models are described for the analysis
      of DNA translocation independent of duplex unwinding. A triplex binding site
      (TBS) was introduced into DNA substrates at precise loci downstream of
      recognition sequences for type IA, IB and IC restriction endonucleases (EcoKI,
      EcoAI and EcoR124I, respectively). Each endonuclease was incubated (without ATP)
      with substrates on which a hexachlorofluoroscein-labelled triplex-forming
      oligonucleotide (HEX-TFO) was pre-bound. Following addition of ATP, 1-D enzyme
      motion resulted in collision with, and displacement of, the HEX-TFO, producing a
      >twofold increase in fluorescent intensity. Alternatively, a decrease in
      anisotropy following displacement of a rhodamine-labelled TFO was monitored.
      Using rapid mixing in a stopped-flow fluorimeter, continuous kinetic profiles
      were produced in which displacement is preceded by a lag-phase, directly
      proportional to the distance moved. For each enzyme, we obtained not only the
      translocation rate but also information on slow isomerisation step(s) at
      initiation. Furthermore, we demonstrated that enzymes deficient in DNA cleavage
      but with maximal ATPase activity showed initiation and translocation rates
      identical to wild-type, confirming that DNA strand breaks are not a pre-requisite
      of motion.

PMID- 15843022
TI  - Crystal structure of human E1 enzyme and its complex with a substrate analog
      reveals the mechanism of its phosphatase/enolase activity.
AB  - Enolase-phosphatase E1 (MASA) is a bifunctional enzyme in the ubiquitous
      methionine salvage pathway that catalyzes the continuous reactions of 2,3-diketo
      5-methylthio-1-phosphopentane to yield the aci-reductone metabolite using Mg2+ as
      cofactor. In this study, we have determined the crystal structure of MASA and its
      complex with a substrate analog to 1.7A resolution by multi-wavelength anomalous
      diffraction and molecular replacement techniques, respectively. The structures
      support the proposed mechanism of phosphatase activity and further suggest the
      probable mechanism of enolization. We establish a model for substrate binding to
      describe in detail the enzymatic reaction and the formation of the transition
      state, which will provide insight into the reaction mechanisms of other enzymes
      in the same family.

PMID- 15843023
TI  - Mechanical stress induced mechanism of microtubule catastrophes.
AB  - Microtubules assembled in vitro from pure tubulin can switch occasionally from
      growing to shrinking states or resume assembly, an unusual behavior termed
      "dynamic instability of microtubule growth". Its origin remains unclear and
      several models have been proposed, including occasional switching of the
      microtubules into energetically unfavorable configurations during assembly. In
      this study, we have asked whether the excess energy accumulated in these
      configurations would be of sufficient magnitude to destabilize the capping region
      that must exist at the end of growing microtubules. For this purpose, we have
      analyzed the frequency distribution of microtubules assembled in vitro from pure
      tubulin, and modeled the different mechanical constraints accumulated in their
      wall. We find that the maximal excess energy that the microtubule lattice can
      store is in the order of 11 kBT per dimer. Configurations that require
      distortions up to approximately 20 kBT are allowed at the expense of a slight
      conformational change, and larger distortions are not observed. Modeling of the
      different elastic deformations suggests that the excess energy is essentially
      induced by protofilament skewing, microtubule radial curvature change and inter
      subunit shearing, distortions that must destabilize further the tubulin subunits
      interactions. These results are consistent with the hypothesis that unfavorable
      closure events may trigger the catastrophes observed at low tubulin concentration
      in vitro. In addition, we propose a novel type of representation that describes
      the stability of microtubule assembly systems, and which might be of considerable
      interest to study the effects of stabilizing and destabilizing factors on
      microtubule structure and dynamics.

PMID- 15843024
TI  - Structural insights into fusidic acid resistance and sensitivity in EF-G.
AB  - Fusidic acid (FA) is a steroid antibiotic commonly used against Gram positive
      bacterial infections. It inhibits protein synthesis by stalling elongation factor
      G (EF-G) on the ribosome after translocation. A significant number of the
      mutations conferring strong FA resistance have been mapped at the interfaces
      between domains G, III and V of EF-G. However, direct information on how such
      mutations affect the structure has hitherto not been available. Here we present
      the crystal structures of two mutants of Thermus thermophilus EF-G, G16V and
      T84A, which exhibit FA hypersensitivity and resistance in vitro, respectively.
      These mutants also have higher and lower affinity for GTP respectively than wild
      type EF-G. The mutations cause significant conformational changes in the switch
      II loop that have opposite effects on the position of a key residue, Phe90, which
      undergoes large conformational changes. This correlates with the importance of
      Phe90 in FA sensitivity reported in previous studies. These structures
      substantiate the importance of the domain G/domain III/domain V interfaces as a
      key component of the FA binding site. The mutations also cause subtle changes in
      the environment of the "P-loop lysine", Lys25. This led us to examine the
      conformation of the equivalent residue in all structures of translational
      GTPases, which revealed that EF-G and eEF2 form a group separate from the others
      and suggested that the role of Lys25 may be different in the two groups.

PMID- 15843025
TI  - Crystal structures of Fms1 and its complex with spermine reveal substrate
      specificity.
AB  - Fms1 is a rate-limiting enzyme for the biosynthesis of pantothenic acid in yeast.
      Fms1 has polyamine oxidase (PAO) activity, which converts spermine into
      spermidine and 3-aminopropanal. The 3-aminopropanal is further oxidized to
      produce beta-alanine, which is necessary for the biosynthesis of pantothenic
      acid. The crystal structures of Fms1 and its complex with the substrate spermine
      have been determined using the single-wavelength anomalous diffraction (SAD)
      phasing method. Fms1 consists of an FAD-binding domain, with Rossmann fold
      topology, and a substrate-binding domain. The active site is a tunnel located at
      the interface of the two domains. The substrate spermine binds to the active site
      mainly via hydrogen bonds and hydrophobic interactions. In the complex, C11 but
      not C9 of spermine is close enough to the catalytic site (N5 of FAD) to be
      oxidized. Therefore, the products are spermidine and 3-aminopropanal, rather than
      3-(aminopropyl) 4-aminobutyraldehyde and 1,3-diaminoprone.

PMID- 15843026
TI  - The MntC crystal structure suggests that import of Mn2+ in cyanobacteria is redox
      controlled.
AB  - The MntC protein is the periplasmic solute-binding protein component of the high
      affinity manganese ATP-binding cassette-type transport system in the
      cyanobacterium Synechocytis PCC sp. 6803. We have determined the structure of
      recombinant MntC at 2.9 A resolution by X-ray crystallography using a combination
      of multi-wavelength anomalous diffraction and molecular replacement. The presence
      of Mn2+ in the metal ion-binding site was ascertained by use of anomalous
      difference electron density maps using diffraction data collected at the Mn
      absorption edge. The MntC protein is similar to previously determined metal ion
      binding, solute-binding proteins with two globular domains connected by an
      extended alpha-helix. However, the metal ion-binding site is asymmetric, with two
      of the four ligating residues (Glu220 and Asp295) situated closer to the ion than
      the two histidine residues (His89 and His154). A unique characteristic of the
      MntC is the existence of a disulfide bond between Cys219 and Cys268. Analysis of
      amino acid sequences of homologous proteins shows that conservation of the
      cysteine residues forming the disulfide bond occurs only in cyanobacterial
      manganese solute-binding proteins. One of the monomers in the MntC asymmetric
      unit trimer is disordered significantly in the globular domain containing the
      disulfide bond. The electron density on the manganese ion and on the disulfide
      bond in this monomer indicates that reduction of this bond changes the relative
      position of the lower domain and of the Glu220 ligand, potentially lowering the
      affinity towards Mn2+. This is confirmed by reduction of the disulfide bond in
      vitro, showing the release of bound Mn2+. We propose that the reduction or
      oxidation state of the disulfide bond can alter the binding affinity of the
      protein towards Mn2+ and thus determine whether these ions will be transported
      into the cytoplasm, or be available for photosystem II biogenesis in the
      periplasm.

PMID- 15843027
TI  - Crystal structures of Mycobacteria tuberculosis and Klebsiella pneumoniae UDP
      galactopyranose mutase in the oxidised state and Klebsiella pneumoniae UDP
      galactopyranose mutase in the (active) reduced state.
AB  - Uridine diphosphogalactofuranose (UDP-Galf) is the precursor of the d
      galactofuranose sugar found in bacterial and parasitic cell walls, including
      those of many pathogens. UDP-Galf is made from UDP-galactopyranose by the enzyme
      UDP-galactopyranose mutase. The enzyme requires the reduced FADH- co-factor for
      activity. The structure of the Mycobacterium tuberculosis mutase with FAD has
      been determined to 2.25 A. The structures of Klebsiella pneumoniae mutase with
      FAD and with FADH- bound have been determined to 2.2 A and 2.35 A resolution,
      respectively. This is the first report of the FADH(-)-containing structure. Two
      flavin-dependent mechanisms for the enzyme have been proposed, one, which
      involves a covalent adduct being formed at the flavin and the other based on
      electron transfer. Using our structural data, we have examined the two
      mechanisms. The electron transfer mechanism is consistent with the structural
      data, not surprisingly, since it makes fewer demands on the precise positioning
      of atoms. A model based on a covalent adduct FAD requires repositioning of the
      enzyme active site and would appear to require the isoalloxazine ring of FADH- to
      buckle in a particular way. However, the FADH- structure reveals that the
      isoalloxazine ring buckles in the opposite sense, this apparently requires the
      covalent adduct to trigger profound conformational changes in the protein or to
      buckle the FADH- opposite to that seen in the apo structure.

PMID- 15843028
TI  - Higher-order molecular packing in amyloid-like fibrils constructed with linear
      arrangements of hydrophobic and hydrogen-bonding side-chains.
AB  - Various mutants of the protein fragment, barnase module-1 (1-24) were
      investigated in order to reveal the structural principle of amyloid-like fibrils.
      By means of circular dichroism spectroscopy, X-ray diffraction, electron
      microscopy, and thioflavin T binding assay, we found that the molecules
      containing two beta-strands and an intervening turn structure are assembled to
      form a cross-beta structure. Stabilization by both the hydrophobic interactions
      and hydrogen bonding between the respective paired side-chains on the coupled
      beta-strands was essential for fibril formation. These two types of interaction
      can also arrange the corresponding residues in lines on both sheet surfaces of
      protofilaments with a cross-beta structure. This leads to the most probable
      fibril structure constructed with the line-matching interactions between
      protofilaments. Consideration of the geometrical symmetry resulted in our finding
      that a limited number of essential models for molecular packing in fibril
      structure are stable, which would rationally explain the occurrence of two or
      three morphologies from an identical molecular species. The ribbon-like fibrils
      exhibited striped texture along the axis, which was assigned to a stacked two
      sheet repeat as a structural unit. The comprehensively proposed structural model,
      that is, the sheet-sheet interaction between left-handed cross-beta structures,
      results in a slightly right-handed twist of beta-sheet stacking, which reasonably
      elucidates the intrinsic sizes of the fibril width and its helical period along
      the fibril axis, as the bias in the orientation of the hydrogen-bonded beta
      strand pair at the lateral edge is larger than that at the central protofilament.

PMID- 15843029
TI  - Pro-sequence and Ca2+-binding: implications for folding and maturation of Ntn
      hydrolase penicillin amidase from E. coli.
AB  - Penicillin amidase (PA) is a bacterial periplasmic enzyme synthesized as a pre
      pro-PA precursor. The pre-sequence mediates membrane translocation. The
      intramolecular pro-sequence is expressed along with the A and B chains but is
      rapidly removed in an autocatalytic manner. In extensive studies we show here
      that the pro-peptide is required for the correct folding of PA. Pro-PA and PA
      unfold via a biphasic transition that is more pronounced in the case of PA.
      According to size-exclusion chromatography and limited proteolysis experiments,
      the inflection observed in the equilibrium unfolding curves corresponds to an
      intermediate in which the N-terminal domain (A-chain) still possesses native-like
      topology, whereas the B-chain is unfolded to a large extent. In a series of in
      vitro experiments with a slow processing mutant pro-PA, we show that the pro
      sequence in cis functions as a folding catalyst and accelerates the folding rate
      by seven orders of magnitude. In the absence of the pro-domain the PA refolds to
      a stable inactive molten globule intermediate that has native-like secondary but
      little tertiary structure. The pro-sequence of the homologous Alcaligenes
      faecalis PA can facilitate the folding of the hydrolase domain of Escherichia
      coli PA when added in trans (as a separate polypeptide chain). The isolated pro
      sequence has a random structure in solution. However, difference circular
      dichroism spectra of native PA and native PA with pro-peptide added in trans
      suggest that the pro-sequence adopts an alpha-helical conformation in the context
      of the mature PA molecule. Furthermore, our results establish that Ca2+, found in
      the crystal structure, is not directly involved in the folding process. The
      cation shifts the equilibrium towards the native state and facilitates the
      autocatalytic processing of the pro-peptide.

PMID- 15843030
TI  - Complex protein targeting to dinoflagellate plastids.
AB  - Protein trafficking pathways to plastids are directed by N-terminal targeting
      peptides. In plants this consists of a relatively simple transit peptide, while
      in organisms with secondary plastids (which reside within the endomembrane
      system) a signal peptide is appended to the transit peptide. Despite amino acid
      compositional differences between organisms, often due to nucleotide biases, the
      features of plastid targeting sequences are generally consistent within species.
      Dinoflagellate algae deviate from this trend. We have conducted an expressed
      sequence tag (EST) survey of the peridinin-plastid containing dinoflagellate
      Heterocapsa triquetra to identify and characterize numerous targeting
      presequences of plastid proteins encoded in the nucleus. Consistent with
      targeting systems present in other secondary plastid-containing organisms, these
      all possess a canonical signal peptide at their N termini, however two major
      classes of transit peptides occur. Both classes possess a common N-terminal
      portion of the transit peptide, but one class of transit peptides contains a
      hydrophobic domain that has been reported to act as a stop-transfer membrane
      anchor, temporarily arresting protein insertion into the endoplasmic reticulum. A
      second class of transit peptide lacks this feature. These two classes are
      represented approximately equally, and for any given protein the class is
      conserved across all dinoflagellate taxa surveyed to date. This dichotomy
      suggests that two mechanisms, perhaps even trafficking routes, may direct
      proteins to dinoflagellate plastids. A four-residue phenylalanine-based motif is
      also a consistent feature of H. triquetra transit peptides, which is an ancient
      feature predating red algae and galucophytes that was lost in green plastids.

PMID- 15843031
TI  - The helically extended SH3 domain of the T cell adaptor protein ADAP is a novel
      lipid interaction domain.
AB  - Adhesion and degranulation-promoting adapter protein (ADAP) is critically
      involved in downstream signalling events triggered by the activation of the T
      cell receptor. Cytokine production, proliferation and integrin clustering of T
      cells are dependent on ADAP function, but the molecular basis for these processes
      is poorly understood. We now show the hSH3 domain of ADAP to be a lipid
      interaction module that binds to acidic lipids, including phosphatidylinositides.
      Positively charged surface patches of the domain preferentially bind to
      polyvalent acidic lipids such as PIP2 or PIP3 over the monovalent PS phospholipid
      and this interaction is dependent on the N-terminal helix of the hSH3 domain
      fold. Basic amino acid side-chains from the SH3 scaffold also contribute to lipid
      binding. In the context of T cell signalling, our findings suggest that ADAP,
      upon recruitment to the cell-cell junction as part of a multiprotein complex,
      directly interacts with phosphoinositide-enriched regions of the plasma membrane.
      Furthermore, the ADAP lipid interaction defines the helically extended SH3
      scaffold as a novel member of membrane interaction domains.

PMID- 15843032
TI  - Leukemia inhibitory factor blocks early differentiation of skeletal muscle cells
      by activating ERK.
AB  - Leukemia inhibitory factor (LIF) is a multifunctional cytokine belonging to the
      interleukin-6 family and has been shown to stimulate regeneration of injured
      skeletal muscle. Although LIF has been shown to stimulate muscle cell
      proliferation, its precise role in differentiation is unclear. Thus, we examined
      the effect of LIF on the differentiation of cultured C2C12 myoblast cells. In
      this study, we used both non-glycosylated LIF expressed in bacteria and
      glycosylated LIF secreted from NIH3T3 cells infected with Ad-LIF. Both non
      glycosylated and glycosylated LIF blocked differentiation of myoblasts as
      measured by expression of myosin heavy chain and myotube formation. Treatment of
      myoblasts with LIF induced phosphorylation of ERK, and the LIF-induced inhibitory
      effect on myogenesis was blocked by pretreatment with U0126, a specific MEK
      inhibitor, and transient transfection with dominant negative (DN)-MEK1. In
      contrast, although LIF activated STAT3, the LIF-induced repression of the MCK
      transcriptional activity was not reversed by pretreatment with AG490, a specific
      Jak kinase inhibitor or transient transfection with DN-STAT3. Additionally, LIF
      exhibited its inhibitory effect on myogenesis only when cells were treated at
      earlier than 12 h after inducing differentiation. Taken together, these results
      suggest that LIF strongly inhibited early myogenic differentiation though
      activation of the ERK signaling pathway and its effect is irrespective of
      glycosylation.

PMID- 15843033
TI  - The molecular mechanism of protecting cells against oxidative stress by 2
      selenium-bridged beta-cyclodextrin with glutathione peroxidase activity.
AB  - Ultraviolet B (UVB) induces apoptosis and lipid peroxidation of NIH3T3 cells by
      producing reactive oxygen species (ROS). Glutathione peroxidase (GPX) is one of
      the most important antioxidant enzymes in organism and it can scavenge ROS. 2
      selenium-bridged beta-cyclodextrin (2-SeCD) is a GPX mimic generated in our lab.
      Its GPX activity is 7.4 U/mumol, which is 7.5 times as much as that of ebselen.
      In this paper, we have established a cell damage system using UVB radiation.
      Using this system, we have determined antioxidant effect of 2-SeCD by comparison
      of malondialdehyde (MDA) and H(2)O(2) contents in NIH3T3 cells before and after
      UVB radiation. Experimental results indicate that 2-SeCD can inhibit lipid
      peroxidation and protect the cells from the damage generated by UVB radiation. To
      evaluate the molecular mechanism of this protection, we determined the effect of
      2-SeCD on the expression of p53 and Bcl-2 in NIH3T3 cells. The results showed
      that 2-SeCD inhibits the increase of p53 expression level and the decrease of
      expression of Bcl-2 induced by UVB radiation. Thus, we have concluded that
      protection of NIH3T3 cells against oxidative stress by 2-SeCD was carried out by
      regulation of the expression of Bcl-2 and p53.

PMID- 15843034
TI  - S-adenosylmethionine (SAMe) modulates interleukin-10 and interleukin-6, but not
      TNF, production via the adenosine (A2) receptor.
AB  - S-adenosylmethionine (SAMe) is the first product in methionine metabolism and
      serves as a precursor for glutathione (GSH) as well as a methyl donor in most
      transmethylation reactions. The administration of exogenous SAMe has beneficial
      effects in many types of liver diseases. One mechanism for the hepatoprotective
      action is its ability to regulate the immune system by modulating cytokine
      production from LPS stimulated monocytes. In the present study, we investigated
      possible mechanism(s) by which exogenous SAMe supplementation modulated
      production of TNF, IL-10 and IL-6 in LPS stimulated RAW 264.7 cells, a murine
      monocyte cell line. Our results demonstrated that exogenous SAMe supplementation
      inhibited TNF production but enhanced both IL-10 and IL-6 production. SAMe
      increased intracellular GSH level, however, N-acetylcysteine (NAC), the GSH pro
      drug, decreased the production of all three cytokines. Importantly, SAMe
      increased intracellular adenosine levels, and exogenous adenosine supplementation
      had effects similar to SAMe on TNF, IL-10 and IL-6 production. 3-Deaza-adenosine
      (DZA), a specific inhibitor of S-adenosylhomocysteine (SAH) hydrolase, blocked
      the elevation of IL-10 and IL-6 production induced by SAMe, which was rescued by
      the addition of exogenous adenosine. Furthermore, the enhancement of LPS
      stimulated IL-10 and IL-6 production by both SAMe and adenosine was inhibited by
      ZM241385, a specific antagonist of the adenosine (A(2)) receptor. Our results
      suggest that increased adenosine levels with subsequent binding to the A(2)
      receptor account, at least in part, for SAMe modulation of IL-10 and IL-6, but
      not TNF production, from LPS stimulated monocytes.

PMID- 15843035
TI  - Regulation of cadmium-induced apoptosis by PKCdelta in U937 human promonocytic
      cells.
AB  - Pulse treatment with cadmium chloride followed by recovery caused apoptosis in
      U937 human promonocytic cells. In addition, the treatment-induced PKCdelta
      translocation from cytosol to membrane fraction, which was already detected at 30
      min of treatment; and also caused PKCdelta cleavage to give a 41-kDa fragment,
      which was detected at 3-6 h of recovery, concomitantly with the execution of
      apoptosis. All these effects were reduced by the PKCdelta-specific inhibitor
      rottlerin. By contrast, rottlerin did not prevent the cadmium-provoked
      stimulation of the stress response (as measured by HSP70 expression), nor
      inhibited the generation of apoptosis by heat-shock, which failed to cause
      PKCdelta translocation. Cadmium chloride rapidly induced p38(MAPK) activation,
      which was not affected by rottlerin. By contrast, the p38(MAPK) inhibitor
      SB203580 reduced PKCdelta translocation and cleavage, indicating that p38(MAPK)
      activation precedes and regulates PKCdelta activation. It is concluded that
      PKCdelta mediates apoptosis induction by cadmium ions via early membrane
      translocation, and also possibly through late kinase proteolytic cleavage and
      phosphorylation on tyrosine residues.

PMID- 15843036
TI  - Caspase-1 activity is required for neuronal differentiation of PC12 cells: cross
      talk between the caspase and calpain systems.
AB  - Previously, we have found that caspase-1 activity is increased during myoblast
      differentiation to myotubes. Here we show that caspase-1 activity is required for
      PC12 differentiation to neuronal-like cells. Caspase-1 is shown to be activated
      (by immunoblotting and by assessing activity in cell extracts) in the PC12 cells
      following the initial stage of differentiation. The inhibition of caspase-1
      arrests PC12 cells at an intermediate stage of differentiation and prevents
      neurite outgrowth in these cells; the inhibition is reversed upon the removal of
      the inhibitor. Calpastatin (calpain endogenous specific inhibitor, and a known
      caspase substrate) is diminished at the later stages of PC12 cell
      differentiation, and diminution is prevented by caspase-1 inhibition. The
      degradation of fodrin (a known caspase and calpain substrate) is found in the
      advanced stage of differentiation. Caspase-1 has been implicated in the
      activation of proinflammatory cytokines, and in cell apoptosis. The involvement
      of caspase-1 in two distinct differentiation processes (myoblast fusion and
      neuronal differentiation of PC12 cells) indicates a function for this caspase in
      differentiation processes, and suggests some common mechanisms underlying caspase
      roles in such processes.

PMID- 15843037
TI  - Proteolytic processing of TGFalpha redirects its mitogenic activity: the membrane
      anchored form is autocrine, the secreted form is paracrine.
AB  - Wild-type transforming growth factor alpha (TGFalpha) expression in lactotrope
      cells in the pituitary gland led to lactotrope-specific pituitary hyperplasia and
      adenomata. To indicate whether the EGF receptor is involved in this TGFalpha
      mediated phenotype, we bred TGFalpha mice with mice expressing the cytoplasmic
      truncated-EGF receptor (EGFR-tr), which is dominant-negative in other models.
      These bitransgenic mice developed pituitary pathology despite expression of the
      dominant-negative receptor. To further characterize this observation, we
      generated two lineages of transgenic mice that overexpress mutant forms of
      TGFalpha: a processed soluble form (s TGFalpha) and a cytoplasmic-deleted form
      (TGFalphaDeltaC). While sTGFalpha expression in lactotrope cells failed to induce
      autocrine lactotrope hyperplasia, the pituitary became very enlarged due to
      proliferation of neighboring interstitial cells. In contrast, the TGFalphaDeltaC
      mice did not develop a phenotype, although the mRNA and protein were present in
      the pituitary and this form of TGFalpha was confirmed to be biologically active
      and targeted properly to the plasma membrane of cultured CHO cells. The results
      suggest that the cytoplasmic domain of TGFalpha is required for autocrine
      parenchymal tumor formation in the pituitary gland. This signal cannot be
      inhibited by the EGFR-tr. Conversely, the released form of TGFalpha appears to
      have primarily paracrine activity.

PMID- 15843038
TI  - Inhibition of endothelial cell movement and tubulogenesis by human recombinant
      soluble melanotransferrin: involvement of the u-PAR/LRP plasminolytic system.
AB  - We have previously demonstrated that human recombinant soluble melanotransferrin
      (hr-sMTf) interacts with the single-chain zymogen pro urokinase-type plasminogen
      activator (scu-PA) and plasminogen. In the present work, the impact of exogenous
      hr-sMTf on endothelial cells (EC) migration and morphogenic differentiation into
      capillary-like structures (tubulogenesis) was assessed. hr-sMTF at 10 nM
      inhibited by 50% the migration and tubulogenesis of human microvessel EC (HMEC
      1). In addition, in hr-sMTf-treated HMEC-1, the expression of both urokinase-type
      plasminogen activator receptor (u-PAR) and low-density lipoprotein receptor
      related protein (LRP) are down-regulated. However, fluorescence-activated cell
      sorting analysis revealed a 25% increase in cell surface u-PAR in hr-sMTf-treated
      HMEC-1, whereas the binding of the urokinase-type plasminogen activator (u
      PA)*plasminogen activator inhibitor-1 (PAI-1) complex is decreased. This reduced
      u-PA-PAI-1 binding is correlated with a strong inhibition of the HMEC-1
      plasminolytic activity, indicating that exogenous hr-sMTf treatment alters the
      internalization and recycling processes of free and active u-PAR at the cellular
      surface. Overall, these results demonstrate that exogenous hr-sMTf affects
      plasminogen activation at the cell surface, thus leading to the inhibition of EC
      movement and tubulogenesis. These results are the first to consider the potential
      use of hr-sMTf as a possible therapeutic agent in angiogenesis-related
      pathologies.

PMID- 15843039
TI  - The aldehyde acrolein induces apoptosis via activation of the mitochondrial
      pathway.
AB  - Acrolein is a highly reactive alpha,beta-unsaturated aldehyde, which is a product
      of lipid peroxidation. It is an environmental pollutant that has been implicated
      in multiple respiratory diseases. Acrolein is produced by the enzymatic oxidative
      deamination of spermine by amine oxidase. Oxidation products of polyamines have
      been involved in the inhibition of cell proliferation, apoptosis, and the
      inhibition of DNA and protein synthesis. The present study investigates the
      mechanism of cell death induced by acrolein. Acrolein induced apoptosis through a
      decrease in mitochondrial membrane potential, the liberation of cytochrome c, the
      activation of initiator caspase-9, and the activation of the effector caspase-7.
      However, acrolein inhibited enzymatic activity of the effector caspase-3,
      although a cleavage of pro-caspase-3 occurred. The activation of caspases-9 and 
      7 was confirmed by the cleavage of their pro-enzyme form by acrolein. Apoptosis
      was inhibited by an inhibitor of caspase-9, but not by an inhibitor of caspase-3.
      The induction of apoptosis by acrolein was confirmed morphologically by the
      condensation of nuclear chromatin and by the cleavage of the inhibitor of caspase
      activated DNase (ICAD), which leads to the liberation of CAD that causes DNA
      fragmentation. These results demonstrate that acrolein causes apoptosis through
      the mitochondrial pathway.

PMID- 15843040
TI  - Pharmacological inhibitors of extracellular signal-regulated protein kinases
      attenuate the apoptotic action of cisplatin in human myeloid leukemia cells via
      glutathione-independent reduction in intracellular drug accumulation.
AB  - It has been reported that inhibition of extracellular signal-regulated protein
      kinases (ERKs) attenuates the toxicity cisplatin (cis-platinum (II)-diammine
      dichloride) in some cell types. This response was here investigated using human
      myeloid leukemia cells. Cisplatin stimulated ERK1/2 phosphorylation and caused
      apoptosis in U-937 promonocytic cells, an effect which was attenuated by the
      MEK/ERK inhibitors PD98059 and U0126. While ERK1/2 activation was a general
      phenomenon, irrespective of the used cell type or antitumour drug, the MEK/ERK
      inhibitors only reduced cisplatin toxicity in human myeloid cells (THP-1, HL-60
      and NB-4), but not in RAW 264.7 mouse macrophages and NRK-52E rat renal tubular
      cells; and failed to reduce the toxicity etoposide, camptothecin, melphalan and
      arsenic trioxide, in U-937 cells. U0126 attenuated cisplatin-DNA binding and
      intracellular peroxide accumulation, which are important regulators of cisplatin
      toxicity. Although cisplatin decreased the intracellular glutathione (GSH)
      content, which was restored by U0126, treatments with GSH-ethyl ester and dl
      buthionine-(S,R)-sulfoximine revealed that GSH does not regulate cisplatin
      toxicity in the present experimental conditions. In spite of it, PD98059 and
      U0126 reduced the intracellular accumulation of cisplatin. These results suggest
      that GSH-independent modulation of drug transport is a major mechanism explaining
      the anti-apoptotic action of MEK/ERK inhibitors in cisplatin-treated myeloid
      cells.

PMID- 15843041
TI  - Dictyostelium CBP3 associates with actin cytoskeleton and is related to slug
      migration.
AB  - Calcium-binding protein 3 (CBP3) expression was up-regulated under the control of
      the actin 15 promoter and down-regulated by RNA interference in Dictyostelium
      discoideum. The overexpression of CBP3 accelerated cell aggregation and formed
      small aggregates and fruiting body. CBP3-inhibited cells showed uneven
      aggregation and increased slug trail lengths toward the directed light, whereas
      CBP3-overexpressing cells showed the opposite phenomena. Under dark condition,
      the enhanced slug trail length was also observed in the CBP3-inhibited cells.
      Yeast two-hybrid screening identified actin 8 as interacting protein with CBP3.
      The interaction between CBP3 and actin was confirmed by beta-galactosidase assay
      and surface plasmon resonance. CBP3 was associated with Triton X-100-insoluble
      cytoskeleton in the presence of Ca(2+) and the interaction of CBP3 with
      cytoskeleton was increased by the addition of Ca(2+). Using fluorescence
      microscopy, CBP3 was also shown to associate with the actin cytoskeleton during
      development. Subcellular fractionation indicated that CBP3 was enriched in
      cytosolic fraction. Taken together, these results suggest that CBP3 interacts
      with actin cytoskeleton and has a role during cell aggregation and slug migration
      of Dictyostelium.

PMID- 15843042
TI  - Prostaglandin D(2) and J(2) induce apoptosis in human leukemia cells via
      activation of the caspase 3 cascade and production of reactive oxygen species.
AB  - The presence of prostaglandins (PGs) has been demonstrated in the processes of
      carcinogenesis and inflammation. In the present study, we found that 12-o
      tetradecanoylphorbol 13-acetate (TPA) induced cyclooxygenase 2 (COX-2), but not
      COX-1, protein expression in HL-60 cells, and the addition of arachidonic acid
      (AA) in the presence or absence of TPA significantly reduced the viability of HL
      60 cells, an effect that was blocked by adding the COX inhibitors, NS398 and
      aspirin. The AA metabolites, PGD(2) and PGJ(2), but not PGE(2) or PGF(2alpha),
      reduced the viability of the human HL60 and Jurkat leukemia cells according to
      the MTT assay and LDH release assay. Apoptotic characteristics including DNA
      fragmentation, apoptotic bodies, and hypodiploid cells were observed in PGD(2)-
      and PGJ(2)-treated leukemia cells. A dose- and time-dependent induction of
      caspase 3 protein procession, and PARP and D4-GDI protein cleavage with
      activation of caspase 3, but not caspase 1, enzyme activity was detected in HL-60
      cells treated with PGD(2) or PGJ(2). Additionally, DNA ladders induced by PGD(2)
      and PGJ(2) were significantly inhibited by the caspase 3 peptidyl inhibitor, Ac
      DEVD-FMK, but not by the caspase 1 peptidyl inhibitor, Ac-YVAD-FMK, in accordance
      with the blocking of caspase 3, PARP, and D4-GDI protein procession. An increase
      in intracellular peroxide levels by PGD(2) and PGJ(2) was identified by the DCHF
      DA assay, and anti-oxidant N-acetyl cysteine (NAC), mannitol (MAN), and tiron
      significantly inhibited cell death induced by PGD(2) and PGJ(2) by reducing
      reactive oxygen species (ROS) production. The PGJ(2) metabolites, 15-deoxy
      Delta(12,14)-PGJ(2) and Delta(12)-PGJ(2), exhibited effective apoptosis-inducing
      activity in HL-60 cells through ROS production via activation of the caspase 3
      cascade. The proliferator-activated receptor-gamma (PPAR-gamma) agonists,
      rosiglitazone (RO), troglitazone (TR), and ciglitazone (CI), induced apoptosis in
      cells which was blocked by the addition of the PPAR-gamma antagonists, GW9662 and
      BADGE, via blocking of caspase 3 and PARP cleavage. However, neither GW9662 nor
      BADGE showed any protective effect on PGD(2)- and PGJ(2)-induced apoptosis. A
      differential apoptotic effect of PGs through ROS production, followed by
      activation of the caspase 3 cascade, was demonstrated.

PMID- 15843043
TI  - Selective decrease of membrane-associated PKC-alpha and PKC-epsilon in response
      to elevated intracellular O-GlcNAc levels in transformed human glial cells.
AB  - Increased flux through the hexosamine biosynthetic pathway (HBP) has been shown
      to affect the activity and translocation of certain protein kinase C (PKC)
      isoforms. It has been suggested that this effect is due to increases in the beta
      O-linked N-acetylglucosamine (O-GlcNAc) modification. Herein, we demonstrate the
      effect of increasing the O-GlcNAc modification on the translocation of select PKC
      isozymes in a human astroglial cell line. Treating cells with either 8 mM d
      glucosamine (GlcN), 5 mM streptozotocin (STZ), or 80 muM O-(2-acetamido-2-deoxy-d
      glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) produced a significant
      increase in the O-GlcNAc modification on both cytosolic and membrane proteins;
      however, both the level and rate of O-GlcNAc increase varied with the compound.
      GlcN treatment resulted in a rapid, transient translocation of PKC-betaII that
      was maximal after 3 h (73+/-8%) and also produced a 48+/-15% decrease in membrane
      associated PKC-epsilon after 9 h of treatment. Similar to GlcN treatment, STZ and
      PUGNAc treatment also resulted in decreased levels of PKC-epsilon in the membrane
      fraction. Significant decreases were seen as early as 5 h and, by 9 h of
      treatment, had decreased by 87+/-6% with STZ and 73+/-7% with PUGNAc. Unlike
      GlcN, both STZ and PUGNAc produced a decrease in PKC-alpha membrane levels by 9 h
      posttreatment (78+/-10% with STZ and 66+/-8% with PUGNAc) while neither compound
      produced any changes in PKC-betaII translocation. In addition, none of the three
      compounds affected membrane levels of PKC-iota. Altogether, these results
      demonstrate a novel link between increased levels of the O-GlcNAc modification
      and the regulation of specific PKC isoforms.

PMID- 15843044
TI  - Ca(2+)-independent phospholipase A2 participates in the vesicular transport of
      milk proteins.
AB  - Changes in the lipid composition of intracellular membranes are believed to take
      part in the molecular processes that sustain traffic between organelles of the
      endocytic and exocytic transport pathways. Here, we investigated the
      participation of the calcium-independent phospholipase A2 in the secretory
      pathway of mammary epithelial cells. Treatment with bromoenol lactone, a suicide
      substrate which interferes with the production of lysophospholipids by the
      calcium-independent phospholipase A2, resulted in the reduction of milk proteins
      secretion. The inhibitor slowed down transport of the caseins from the
      endoplasmic reticulum to the Golgi apparatus and affected the distribution of p58
      and p23, indicating that the optimal process of transport of these proteins
      between the endoplasmic reticulum, the endoplasmic reticulum/Golgi intermediate
      compartment and/or the cis-side of the Golgi was dependent upon the production of
      lysolipids. Moreover, bromoenol lactone was found to delay the rate of protein
      transport from the trans-Golgi network to the plasma membrane. Concomitantly,
      membrane-bound structures containing casein accumulated in the juxtanuclear Golgi
      region. We concluded from these results that efficient formation of post-Golgi
      carriers also requires the phospholipase activity. These data further support the
      participation of calcium-independent phospholipase A2 in membrane trafficking and
      shed a new light on the tubulo/vesicular transport of milk protein through the
      secretory pathway.

PMID- 15843045
TI  - Purine nucleoside-mediated protection of chemical hypoxia-induced neuronal
      injuries involves p42/44 MAPK activation.
AB  - Hypoxia in brain may lead to cell death by apoptosis and necrosis. Concomitant is
      the formation of purine nucleosides, e.g. adenosine, a powerful endogenous
      neuroprotectant. Despite vigorous studies, many aspects of the mechanisms
      involved in purine-based protection are still unclear. In this study, we wanted
      to investigate the effect of purine nucleosides on cellular responses to chemical
      hypoxia. O(2)-sensitive neuronal pheochromocytoma (PC12)-cells, which are widely
      used as a model system for sympathetic ganglion-like neurons, were subjected to
      chemical hypoxia induced with rotenone, an inhibitor of mitochondrial complex I.
      Adenosine and its relatives guanosine and inosine were tested for their
      neuroprotective capability to improve neurite outgrowth and viability. In
      addition, cell lysates were analyzed for mitogen-activated-protein-kinases (MAPK)
      activation by anti-active and anti-total MAPKinase immunoblotting. Adenosine,
      guanosine and inosine significantly inhibited the loss of viability after hypoxic
      insult. In combination with NGF, purine nucleosides also partially rescued
      neurite outgrowth. The MEK-1/-2 inhibitor PD098059 inhibited purine nucleoside
      mediated protection up to 85.23% and also markedly decreased neurite formation
      induced by NGF and purine nucleosides in hypoxic cells. Immunoblot analysis
      revealed a strong activation of MAPKinase upon incubation of cells with
      adenosine, guanosine or inosine. In combination with NGF an additive effect was
      observed. Results suggested that activation of the MAPKinase pathway plays a
      vital role in purine nucleoside-mediated protection of neuronal cells following
      hypoxic insult.

PMID- 15843046
TI  - Convulsant activity and neurochemical alterations induced by a fraction obtained
      from fruit Averrhoa carambola (Oxalidaceae: Geraniales).
AB  - We obtained a neurotoxic fraction (AcTx) from star fruit (Averrhoa carambola) and
      studied its effects on GABAergic and glutamatergic transmission systems. AcTx had
      no effect on GABA/glutamate uptake or release, or on glutamate binding. However,
      it specifically inhibited GABA binding in a concentration-dependent manner
      (IC(50)=0.89muM). Video-electroencephalogram recordings demonstrated that
      following cortical administration of AcTx, animals showed behavioral changes,
      including tonic-clonic seizures, evolving into status epilepticus, accompanied by
      cortical epileptiform activity. Chemical characterization of AcTx showed that
      this compound is a nonproteic molecule with a molecular weight less than 500,
      differing from oxalic acid. This neurotoxic fraction of star fruit may be
      considered a new tool for neurochemical and neuroethological research.

PMID- 15843047
TI  - Vinpocetine blockade of sodium channels inhibits the rise in sodium and calcium
      induced by 4-aminopyridine in synaptosomes.
AB  - The objective of this study was to get a more understandable picture of the
      mechanism underlying the anticonvulsant action of vinpocetine. The question of
      how the cerebral excitability is affected was investigated by determining the
      effect of vinpocetine on the changes on the internal concentrations of Na(+)
      (Na(i)) and Ca(2+) (Ca(i)) induced by different concentrations of the convulsing
      agent 4-aminopyridine (4-AP) in striatal isolated nerve endings. The cytosolic
      concentrations of Na(i) and Ca(i) were detected fluorimetrically with sodium
      binding benzofuran isophthalate (SBFI) and fura-2, respectively. Vinpocetine,
      like the Na(+) channel blocker, tetrodotoxin, abolished the increase in Na(i)
      induced by 0.1 mM 4-AP and only inhibited in 30% the rise in Na(i) induced by 1mM
      4-AP. In contrast with the different sensitivity of the rise in Na(i) induced by
      0.1 and 1mM 4-AP to vinpocetine and tetrodotoxin, the rise in Ca(i) induced by
      the two concentrations of 4-AP was markedly inhibited by vinpocetine (and
      tetrodotoxin), indicating that only the voltage-sensitive sodium channels (VSSC)
      mediated fraction of the rise in Na(i) induced by 4-AP is linked with the
      activation of pre-synaptic Ca(2+) channels. The elevation of Ca(2+) induced by
      high K(+) (30 mM) does not require a Na(+) gradient and is vinpocetine and
      tetrodotoxin insensitive. In contrast, the elevation of Ca(i) induced by 4-AP,
      requires a physiological (out/in) Na(+) gradient and is vinpocetine and
      tetrodotoxin-sensitive. It is concluded that by blocking the tetrodotoxin
      sensitive fraction of the rise in Na(i) induced by 4-AP, vinpocetine inhibits the
      concomitant rise in Ca(i) induced by 4-AP. The inhibitory effect of vinpocetine
      on pre-synaptic voltage-sensitive sodium channels may underlie the in vivo
      anticonvulsant action of vinpocetine.

PMID- 15843048
TI  - Phenylarsine oxide is able to dissipate synaptic vesicle acidic pool.
AB  - Phenylarsine oxide (PAO) has a number of targets in the neurons, one of them is
      exocytotic process. In this study, we have focused on the mechanisms of
      phenylarsine oxide action on Ca(2+)-dependent and Ca(2+)-independent
      neurotransmitter release from rat brain synaptosomes. We investigated the
      influence of phenylarsine oxide on: (i) l-[(14)C]glutamate and [(3)H]GABA release
      and uptake; (ii) plasma membrane potential using a potential-sensitive
      fluorescent probe rhodamine 6G; (iii) exo/endocytotic process using a pH
      sensitive fluorescent probe acridine orange (AO). It has been found that
      phenylarsine oxide induced deacidification of synaptic vesicles. This effect was
      completely abolished by preliminary treatment of synaptosomes with a protonophore
      FCCP indicating that both reagents injured a proton electrochemical gradient.
      Dissipation of the proton gradient by low concentrations of phenylarsine oxide
      (not exceed 1 microM) did not prevent KCl-triggered exocytotic response, but
      essentially modified endocytotic one. At higher concentrations of phenylarsine
      oxide (up to 10 microM), the proton gradient dissipation was intensified and the
      exocytotic response was fully abolished. The reagent did not change plasma
      membrane potential, but depolarized mitochondria. It also caused potent
      inhibition of the Ca(2+)-stimulated l-[(14)C]glutamate and [(3)H]GABA release and
      increase the Ca(2+)-independent release of l-[(14)C]glutamate, but not of
      [(3)H]GABA. Disulfide-reducing reagents (dithiothreitol and beta-mercaptoethanol)
      completely prevented phenylarsine oxide-evoked injuries. They could also restore
      the initial levels of the mitochondrial potential, the exocytotic response to KCl
      and the release and uptake of neurotransmitters. Our data provide the evidence
      that phenylarsine oxide causes dissipation of synaptic vesicle acidic pool
      resulting in the reduction of vesicle filling and as consequence in attenuation
      of Ca(2+)-stimulated neurotransmitter release.

PMID- 15843049
TI  - Soluble interleukin-1 receptor type II, IL-18 and caspase-1 in mild cognitive
      impairment and severe Alzheimer's disease.
AB  - In the present study, we have determined levels of soluble interleukin-1 (IL-1)
      receptor type II (sIL-1RII), interleukin-18 (IL-18) and caspase-1 in
      cerebrospinal fluid and serum from mild cognitive impairment patients that later
      progressed to Alzheimer's disease (AD) and severe AD patients. Previous studies
      have shown that a chronic local inflammatory process is a part of AD
      neuropathology. In this process, activated microglial production of IL-1 seems to
      play an important role. In a previous study, we have shown increased levels of
      sIL-1RII in CSF from AD patients in a mild-moderate disease stage. In the present
      study, we found no significant differences in CSF or serum levels of sIL-1RII in
      either mild cognitive impairment or advanced AD patients as compared to control
      subjects. Likewise, there was no significant difference between mild cognitive
      impairment and severe AD patients. The same was true for caspase-1 and IL-18
      serum levels, whereas CSF levels of caspase-1 and IL-18 were below detection
      limits. Our data indicate that the IL-1 system is relatively intact in the early
      and late stages of AD.

PMID- 15843050
TI  - Distinct modulation of a gene expression of the type 1 and 2 IP(3) receptors by
      retinoic acid in brain areas.
AB  - Inositol 1,4,5-trisphosphate (IP(3)) receptors belong to the intracellular
      calcium channels that release calcium from the intracellular stores after binding
      IP(3). Three types of IP(3) receptors occurred in a tissue specific manner and
      different promoters direct their gene expression. Thus, understanding of the
      transcriptional regulation is the first step towards comprehension of the
      function of these receptors. Since the retinoic acid activates RARE and AP2
      transcription factors, the present study focuses on determination of whether or
      not expression of type 1 and 2 IP(3) receptors is modulated by retinoic acid in
      selected brain areas. We have found that mRNA levels of the type 1 IP(3)
      receptors were decreased significantly in cerebellum and hypothalamus, but not in
      the brain stem of rats treated with retinoic acid, compared to untreated
      littermates. The mRNA levels of the type 2 IP(3) receptor were significantly
      decreased in all tested tissues, cerebellum, hypothalamus, and also in brain stem
      after the treatment with retinoic acid. These results show that gene expression
      of both type 1 and 2 IP(3) receptors is regulated by retinoic acid, although the
      effect of retinoic acid on mRNA levels of the type 1 IP(3) receptors is dependent
      on brain area.

PMID- 15843051
TI  - Age related changes of various markers of astrocytes in senescence-accelerated
      mice hippocampus.
AB  - Astrocytes play a critical role in maintaining normal brain physiology during
      development and in adulthood, while to date the changes of astrocytes during
      aging and their effects on age-related functional decline have not been well
      understood. This study used immunohistochemistry, western blot, and reverse
      transcriptase polymerase chain reaction techniques to investigate the expression
      of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and S100
      beta proteins and mRNAs in the hippocampi of 3 months old and 16 months old
      senescence-accelerated-prone mice (SAMP8) and senescence-accelerated-resistant
      mice (SAMR1). The results showed significant age-related increases in both
      protein and mRNA levels of GFAP in the hippocampi of aged SAMP8 and SAMR1. As
      well, the GFAP of aged SAMP8 was significantly greater than that of aged SAMR1.
      However, no such increase was observed for either GS or S100 beta. These results
      suggested that GFAP, rather than GS or S100 beta, played a more important role in
      the age related deficits in learning and memory.

PMID- 15843052
TI  - Abeta(31-35) peptide induce apoptosis in PC 12 cells: contrast with Abeta(25-35)
      peptide and examination of underlying mechanisms.
AB  - The toxic behaviour of the two shorter sequences of the native Abeta amyloid
      peptide required for cytotoxicity i.e., Abeta(31-35) and Abeta(25-35) peptides,
      was studied. We have shown that Abeta(31-35) peptide induces neurotoxicity in
      undifferentiated PC 12 cell via an apoptotic cell death pathway, including
      caspase activation and DNA fragmentation. Abeta(25-35) peptide, like the shorter
      amyloid peptide has the ability to induce neurotoxicity, as evaluated by the MTS
      reduction assay and by adherent cell count, but the Abeta(25-35) peptide-induced
      neurotoxicity is not associated with any biochemical features of apoptosis. The
      differences observed between the neurotoxic properties of Abeta(31-35) and
      Abeta(25-35) peptides might result on their different ability to be internalised
      within the neuronal cells. Furthermore, this study reveals that the redox state
      of methionine residue, C-terminal in Abeta(31-35) and Abeta(25-35) peptides
      affect in a different way the toxic behaviour of these two short amyloid
      fragments. Taken together our results suggest that Abeta(31-35) peptide induces
      cell death by apoptosis, unlike the Abeta(25-35) peptide and that role played by
      methionine-35 in Abeta induced neurotoxicity might be related to the Abeta
      aggregation state.

PMID- 15843053
TI  - Association study of the chemokine, CXC motif, ligand 1 (CXCL1) gene with
      sporadic Alzheimer's disease in a Japanese population.
AB  - Inflammation is profoundly involved in the development of Alzheimer's disease
      (AD) and other neurodegenerative diseases. Chemokine, CXC motif, ligand 1 (CXCL1;
      or GRO1) is an inflammatory cytokine and appears to be implicated in the
      pathogenesis of AD. It is of interest and importance to see if the CXCL1 gene,
      mapped on chromosome 4q12-q13, has potential for conferring the predisposition to
      AD. Here we report on an association study of the CXCL1 gene with sporadic AD
      patients in a Japanese population; three single nucleotide polymorphisms (SNPs)
      in the CXCL1 locus were investigated in 103 AD patients and 130 healthy
      individuals. The results indicate that neither genotype frequencies nor allele
      frequencies of the examined SNPs attained statistical significance even after
      being stratified by the presence or absence of the Apolipoprotein E epsilon4
      allele. Therefore, the data presented here suggests that the CXCL1 gene could not
      be associated with the susceptibility to AD in a Japanese population.

PMID- 15843054
TI  - Delocalization of the multifunctional RNA splicing factor TLS/FUS in hippocampal
      neurones: exclusion from the nucleus and accumulation in dendritic granules and
      spine heads.
AB  - Long-term synaptic change in the cortex and the hippocampus is believed to
      require the highly localized delivery and translation of mRNAs in the dendritic
      shafts and spines. The molecular interactions that underlie local signalling
      between synapses and mRNAs are still largely undefined. After purification from
      total brain extracts, the NMDA receptor is known to be associated with numerous
      proteins, including the multifunctional RNA-binding factor TLS (also called FUS).
      In non-neural tissue, TLS is a vital nuclear protein with roles in DNA repair,
      homologous recombination, transcriptional regulation and pre-mRNA processing. We
      have examined the distribution of TLS in hippocampal neurones, both in the adult
      brain and in mature primary cultures, using subcellular fractionation and
      immunofluorescence techniques. TLS immunoreactivity is largely excluded from the
      neuronal nucleus and is found in the cytosol and in somatodendritic particles. In
      some of these particles, TLS colocalizes with Sam68, a nuclear RNA-binding
      protein that we previously showed is incorporated into dendritic RNA granules.
      Some of the TLS clusters also colocalize with NMDA receptor clusters. Finally,
      TLS clusters are occasionally seen within spine heads. The apparent removal of
      TLS from the nucleus might result in specific patterns of mRNA transcription or
      splicing in hippocampal neurones. TLS may also contribute to steering, anchoring
      or regulating mRNAs at synaptic sites.

PMID- 15843055
TI  - Conditioned medium of the primary culture of rat choroid plexus epithelial
      (modified ependymal) cells enhances neurite outgrowth and survival of hippocampal
      neurons.
AB  - The choroid plexus epithelial (modified ependymal) cells (CPECs) are specialized
      for cerebrospinal fluid (CSF) production and serve as blood-CSF barrier. It is
      suggested that, in addition to CSF production, the CPECs may regulate CNS
      function through expression of secretory factors into CSF. There have been
      reports that the CPECs express various types of factors including growth factors.
      However, the actual effects of the molecules produced and secreted from the CPECs
      on the central nervous system (CNS) are virtually unknown both in vivo and in
      vitro. With the use of pure culture of CPECs, we demonstrated that the
      conditioned medium (CM) from CPECs can enhance neurite outgrowth and survival of
      cultured neurons derived from rat hippocampus on postnatal day 1 in 24-h
      cultures. The effect of the CM was retained in fractions that contains complex of
      molecules larger than 50kDa in native condition with ultrafiltration method and
      disappeared by trypsin digestion. The results of the present study indicate that
      CPECs can support the survival and function of neurons in vitro by secreting
      factors that are likely to be of peptide/protein nature rather than small
      chemicals.

PMID- 15843056
TI  - 5-HT2A and muscarinic receptors in schizophrenia: a postmortem study.
AB  - Although evidence suggests that 5-HT(2A) and muscarinic M1/M4 receptors are
      implicated in the pathology of schizophrenia, the results are not conclusive. In
      the present study we tested the hypothesis that binding of 5-HT(2A) and M1/M4
      receptors is altered in the postmortem brain of schizophrenia subjects.
      Quantitative autoradiography was employed to measure [(3)H]ketanserin binding to
      5-HT(2A) receptors and [(3)H]pirenzepine binding to both M1 and M4 receptors in
      Brodmann's area 9 (BA9), caudate/putamen, and the hippocampal formation from six
      schizophrenic and six control subjects. A significant reduction in the density of
      5HT(2A) receptors in BA 9 of schizophrenic subjects was observed (p=0.036). No
      significant difference was observed in the density of 5HT(2A) receptors in the
      hippocampus or caudate/putamen between the two groups. No significant changes in
      the density of M1/M4 receptors was observed in these three regions between the
      two groups. These findings support a possible involvement of the serotonergic
      system in the pathology of schizophrenia.

PMID- 15843057
TI  - Involvement of pre- and post-synaptic serotonergic receptors of dorsal raphe
      nucleus neural network in the control of the sweet-substance-induced analgesia in
      adult Rattus norvegicus (Rodentia, Muridae).
AB  - In order to investigate the effects of monoaminergic mechanisms of the dorsal
      raphe nucleus on the elaboration and control of sweet-substance-induced
      antinociception, male albino Wistar rats weighing 180-200 g received sucrose
      solution (250 g/L) for 14 days as their only source of liquid. After the chronic
      consumption of sucrose solution, each animal was pretreated with unilateral
      microinjection of methiothepin mesylate (5.0 microg/0.2 microL), or methysergide
      maleate (5.0 microg/0.2 microL) in the dorsal raphe nucleus. Each rat consumed an
      average of 15.6g sucrose/day. Their tail withdrawal latencies in the tail-flick
      test were measured immediately before and after this treatment. An analgesia
      index was calculated from the withdrawal latencies before and after the
      pharmacological treatment. The blockade of serotonergic receptor in the dorsal
      raphe nucleus with methysergide after the chronic intake of sucrose decreased the
      sweet-induced antinociception. However, microinjections of methiothepin in the
      dorsal raphe nucleus did not cause a similar effect on the tail-flick latencies
      after the chronic intake of sucrose solution, increasing the sweet-substance
      induced analgesia. These results indicate the involvement of serotonin as a
      neurotransmitter in the sucrose-produced antinociception. Considering that the
      blockade of pre-synaptic serotonergic receptors of the neural networks of the
      dorsal raphe nucleus with methiothepin did not decrease the sweet-substance
      induced antinociception, and the central blockade of post-synaptic serotonergic
      receptors decreased the sucrose-induced analgesia, the modulation of the release
      of serotonin in the neural substrate of the dorsal raphe nucleus seems to be
      crucial for the organization of this interesting antinociceptive process.

PMID- 15843058
TI  - Recordings from the rat locus coeruleus during acute vagal nerve stimulation in
      the anaesthetised rat.
AB  - Vagal nerve stimulation (VNS) is used as a treatment for Epilepsy and is
      currently under investigation as a treatment for depression (see [M.S. George, Z.
      Nahas, X. Li, F.A. Kozel, B. Anderson, K. Yamanaka, J.H. Chae, M.J. Foust, Novel
      treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS),
      Semin. Clin. Neuropsychiatry 7 (2002) 293-304; M.S. George, A.J. Rush, H.A.
      Sackeim, L.B. Marangell, Vagus nerve stimulation (VNS): utility in
      neuropsychiatric disorders, Int. J. Neuropsychopharmacol. 6 (2003) 73-83] for
      reviews). The mechanism of action of VNS is not fully understood [E. Ben
      Menachem, Vagus-nerve stimulation for the treatment of epilepsy, Lancet Neurol. 1
      (2002) 477-482] despite numerous imaging investigations (see [E. Ben-Menachem,
      Vagus-nerve stimulation for the treatment of epilepsy, Lancet Neurol. 1 (2002)
      477-482; M.S. George, Z. Nahas, X. Li, F.A. Kozel, B. Anderson, K. Yamanaka, J.H.
      Chae, M.J. Foust, Novel treatments of mood disorders based on brain circuitry
      (ECT, MST, TMS, VNS, DBS), Semin. Clin. Neuropsychiatry 7 (2002) 293-304; M.S.
      George, A.J. Rush, H.A. Sackeim, L.B. Marangell, Vagus nerve stimulation (VNS):
      utility in neuropsychiatric disorders, Int J Neuropsychopharmacol 6 (2003) 73-83;
      M.S. George, H.A. Sackeim, L.B. Marangell, M.M. Husain, Z. Nahas, S.H. Lisanby,
      J.C. Ballenger, A.J. Rush, Vagus nerve stimulation. A potential therapy for
      resistant depression? Psychiatr. Clin. North Am. 23 (2000) 757-783] for reviews).
      However, there is some evidence to suggest that the locus coeruleus may play a
      role modulating the effects of VNS. This study investigated the effects of VNS
      (0.3mA), of sufficient intensity to recruit the A and B fibre components of the
      vagus [D.M. Woodbury, J.W. Woodbury, Effects of vagal stimulation on
      experimentally induced seizures in rats, Epilepsia 31 (Suppl. 2) (1990) S7-S19],
      on the discharge rate of single neurons from the locus coeruleus. This study is
      the first to demonstrate a direct neuronal response from the locus coeruleus
      following acute challenge of VNS in the anaesthetised rat. The results of this
      study indicate that neuronal activity of the locus coeruleus is modulated by VNS.
      This pathway through the locus coeruleus may be significant for mediating the
      clinical effects of VNS.

PMID- 15843059
TI  - Aversive effects elicited by electrical stimulation of the inferior colliculus in
      normal and audiogenic seizure susceptible rats.
AB  - Trains of electrical stimulations were applied to the dorsal or ventral part of
      the inferior colliculus (IC) of audiogenic seizure susceptible rats from the AGSR
      strain. Threshold and duration of wild running (WR), were evaluated in the first
      experiment. All stimulation sites elicited WR, even in normal control rats.
      Stimulation of the IC of AGSR rats required a lower quantity of current, i.e.,
      such brain sites were more sensitive to the current, than normal controls. The
      duration of post-stimulus WR was shorter in AGSR rats. Lower quantities of
      current applied to the ventral IC were needed to elicit WR than to the dorsal IC
      in AGSR rats. In a second experiment, using the same stimulations sites in the
      same rats, the emotional effect of the stimulation was tested through an
      instrumental learning procedure (switch-off paradigm) in which the rat was
      trained to press a bar to put an end to the stimulation. Both dorsal and ventral
      IC stimulation sites sustained switch-off behavior in AGSR rats, but only ventral
      IC stimulation sites sustained switch-off learning in control rats.

PMID- 15843060
TI  - Production of NGF, BDNF and GDNF in mouse astrocyte cultures is strongly enhanced
      by a cerebral vasodilator, ifenprodil.
AB  - Ifenprodil, a non-competitive NMDA-receptor antagonist, has been shown to exhibit
      marked cytoprotective activities in animal models for focal ischemia and
      Parkinson's disease. To test the hypothesis that the cytoprotective effect is due
      to the release of neurotrophic factors (NTFs), we examined the effects of
      ifenprodil on the NTF contents in mouse astrocyte cultures. The results revealed
      that ifenprodil strongly enhanced the production of nerve growth factor (NGF),
      brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic
      factor (GDNF) in these cultures. The ifenprodil-induced NGF secretion was found
      to be partially mediated by the activation of protein kinase C (PKC) and p42/p44
      mitogen-activated protein (MAP) kinase cascade pathways. These findings suggest
      that the cytoprotective effects of ifenprodil are probably attributed to enhanced
      secretion of these NTFs from astrocytes.

PMID- 15843061
TI  - Ruffed cells identified in the adult zebrafish olfactory bulb.
AB  - The morphology and distribution of ruffed cells was examined in the olfactory
      bulb of adult zebrafish, Danio rerio, using retrograde tract tracing and Golgi
      Kopsch techniques. The neurons had variable-shaped soma that ranged in size from
      7 to 15 microm in diameter. There was an obvious protrusion of the membrane, a
      ruff, near the initial portion of the axon, and the cells appeared to be
      distributed primarily in the glomerular layer and superficial internal cell
      layer. This cell type has been described for a number of teleosts, but not for
      other animal groups. While the presence of ruffed cells in all teleosts has been
      suggested, the existence of this cell type in zebrafish was uncertain until now.
      This new evidence may provide additional insight into olfactory coding and
      processing in this key model system.

PMID- 15843062
TI  - Mutations in the pantothenate kinase gene PANK2 are not associated with Parkinson
      disease.
AB  - Pantothenate kinase-associated neurodegeneration (PKAN) may serve as a model for
      Parkinson disease (PD) since many PKAN patients suffer from parkinsonism and both
      conditions lead to iron accumulation in the basal ganglia. We screened the gene
      coding for pantothenate kinase 2 (PANK2) for sequence variants in PD. We found no
      mutations in 67 PD patients with affected sibs or early-onset disease. Moreover,
      PANK2 polymorphisms were not associated with late-onset idiopathic PD in 339
      patients. We conclude that PANK2 variants exert, if any, only a very small effect
      in the genetic risk of PD.

PMID- 15843063
TI  - An autosomal genomic screen for dementia in an extended Amish family.
AB  - Apolipoprotein E (APOE) is the only universally confirmed susceptibility gene for
      late-onset Alzheimer disease (LOAD), although many loci are believed to modulate
      LOAD risk. The genetic homogeneity of isolated populations, such as the Amish,
      potentially provide increased power to identify LOAD susceptibility genes.
      Population homogeneity in these special populations may reduce the total number
      of susceptibility genes contributing to the complex disorder, thereby increasing
      the ability to identify any one susceptibility gene. Dementia in the Amish is
      clinically indistinguishable from LOAD in the general population. Previous
      studies in the Amish demonstrated a significantly decreased frequency of the APOE
      4 susceptibility allele, but significant familial clustering of dementia [M.A.
      Pericak-Vance, C.C. Johnson, J.B. Rimmler, A.M. Saunders, L.C. Robinson, E.G.
      D'Hondt, C.E. Jackson, J.L. Haines, Alzheimer's disease and apolipoprotein E-4
      allele in an Amish population, Ann. Neurol. 39 (1996) 700-704]. These data
      suggested that a genetic etiology independent of APOE may underlie the dementia
      observed in this population. In the present analysis, we focused on a large,
      multiplex, inbred Amish family (24 sampled individuals; 10 of whom are affected).
      We completed a genomic screen to identify novel LOAD loci (n=316 genetic
      markers), using both model-dependent "affecteds-only" analysis (dominant and
      recessive) and model-independent affected relative pair analysis. Interesting
      results (lod>1.5 or p<0.01) were obtained for markers on eight chromosomes (2q,
      5q, 6q, 7p, 8p, 8q, 11p, 18p, 18q, and 19q). The highest overall score was a
      multipoint lod score of 3.1 on chromosome 11p. Most regions we identified were
      not previously detected by genomic screens of outbred populations and may
      represent population-specific susceptibilities to LOAD. These loci are currently
      under further investigation in a study of LOAD including additional Amish
      families.

PMID- 15843064
TI  - The multi-herbal formula Guibi-tang enhances memory and increases cell
      proliferation in the rat hippocampus.
AB  - Guibi-tang (GBT) is a multi-herbal medicinal formula that has been used to treat
      amnesia in the traditional Korean medicine system for hundreds of years. In this
      study, we investigated the effects of GBT on learning and memory function in
      Wistar rats by using the foot shock passive avoidance test. In addition, cell
      proliferation was examined using 5-bromo-2-deoxyuridine (BrdU) uptake and
      immunostaining in the dentate gyrus of the rat hippocampus after oral
      administration of GBT. In the passive avoidance test, the retention time of the
      GBT-treated group was significantly longer (almost 2.5-fold) than that of the
      control group. The number of BrdU-immunoreactive cells in the dentate gyrus was
      significantly higher in the GBT-treated group (almost twofold) than in the
      control group. These results suggest that administration of GBT to rats not only
      improves learning and memory but also increases the proliferation of cells in the
      dentate gyrus of the hippocampus.

PMID- 15843065
TI  - Spinal blockade of TNF blocks spinal nerve ligation-induced increases in spinal P
      p38.
AB  - Spinal nerve ligation (SNL) results in a profound long lasting allodynia and
      increases in phosphorylated p38 in dorsal root ganglia (DRG) neurons and spinal
      cord microglia. We have previously shown that systemic etanercept, a tumor
      necrosis factor (TNF) antagonist, reduced allodynia by 42% and blocked SNL
      induced increases in P-p38 levels in the L5 and L6 DRG, but not in the
      ipsilateral lumbar spinal cord. The present experiments demonstrated that
      intrathecal etanercept (100 microg) prevents SNL-induced increased levels of
      spinal P-p38. Pretreatment, but not posttreatment, with intrathecal etanercept
      (100 microg), given every third day, reduced mechanical allodynia by 50%. This
      therapeutic benefit was maintained for at least 7 days after cessation of
      treatment. Combined systemic and intrathecal administration of etanercept was no
      more effective than intrathecal treatment alone. These data imply that TNF
      provides the trigger for phosphorylation of p38 in both DRG neurons and spinal
      microglia.

PMID- 15843066
TI  - Near-ultraviolet light perceived by the retina generates the signal suppressing
      melatonin synthesis in the chick pineal gland-an involvement of NMDA glutamate
      receptors.
AB  - Exposure of dark-adapted chicks to near ultraviolet (UV-A) light significantly
      decreased melatonin (MEL) content and the activity of serotonin N
      acetyltransferase (AA-NAT; the penultimate and key regulatory enzyme in MEL
      production) in the pineal glands. Significant reduction in MEL level and AA-NAT
      activity was also found in pineals of animals whose heads were covered with black
      opaque tape, an observation suggesting that in the chicken UV-A light perceived
      by the eyes alone is capable of affecting MEL synthesis in the pineal gland.
      Covering the chick's eyes, in addition to the head, totally blocked the studied
      UV-A action. Although SCH 23390 (a selective D1-dopamine receptor antagonist),
      injected directly into both eyes at a dose of 10 nmol/eye, prevented the decline
      in pineal AA-NAT activity produced by retinal illumination with white light, the
      drug did not modify the UV-A light-evoked decrease in the enzyme activity. MK-801
      (a selective antagonist of NMDA glutamate receptors; 1 nmol/eye) abolished the
      suppressive action of UV-A light on pineal AA-NAT activity, but it was inactive
      in the case of white light. Intraocularly injected sulpiride and CNQX (selective
      antagonists of D2-dopamine and AMPA/kainite glutamate receptors, respectively)
      had no effect on the actions of both UV-A and white light (acting on the eyes
      only) on pineal AA-NAT activity. It is concluded that in the chick retinally
      perceived UV-A light generates a signal which suppresses MEL production in the
      pineal gland. At the level of the retina, such signal does not involve dopamine,
      but is dependent on the stimulation of NMDA glutamate receptors.

PMID- 15843067
TI  - Dorsal column lesion reduces mechanical allodynia in the induction, but not the
      maintenance, phase in spinal hemisected rats.
AB  - The dorsal column-medial lemniscal (DC-ML) system is known to be a route of
      ascending input signals for mechanical allodynia following peripheral nerve
      injury. We examined whether the pain signals after spinal hemisection were
      transmitted via the DC-ML system in the induction and maintenance phases of the
      neuropathic pain. Under enflurane anesthesia, rats were subjected to spinal
      hemisection at T13 level and bilateral DC lesion was made at T8 level 1 day or 3
      weeks after the hemisection. The DC lesion 1 day after the hemisection
      significantly reduced the mechanical, but not cold, allodynia, whereas the DC
      lesion 3 weeks after the hemisection did not change both mechanical and cold
      allodynia. These results suggest that the signals for mechanical allodynia
      following spinal hemisection should be transmitted via the DC-ML system in the
      induction, but not maintenance, phase.

PMID- 15843068
TI  - The effect of 1/f fluctuation in inter-stimulus intervals on auditory evoked
      mismatch field.
AB  - This study focused on the effect of regularity of environmental stimuli on the
      informational order extracting function of human brain. The regularity of
      environmental stimuli can be described with the exponent n of the fluctuation
      1/f(n). We studied the effect of the exponent of the fluctuation in the inter
      stimulus interval (ISI) on the elicitation of auditory evoked mismatch fields
      (MMF) with two sounds with alternating frequency. ISI times were given by three
      types of fluctuation, 1/f(0), 1/f(1), 1/f(2), and with a fixed interval
      (1/f(infinity)). The root mean square (RMS) value of the MMF increased
      significantly (F(3/9)=4.95, p=0.027) with increases in the exponent of the
      fluctuation. Increments in the regularity of the fluctuation provoked enhancement
      of the MMF, which reflected the production of a memory trace, based on the
      anticipation of the stimulus timing. The gradient of the curve, indicating the
      ratio of increments between the MMF and the exponent of fluctuation, can express
      a subject's capability to extract regularity from fluctuating stimuli.

PMID- 15843069
TI  - Investigation of the effect of brain-derived neurotrophic factor (BDNF)
      polymorphisms on the risk of late-onset Alzheimer's disease (AD) and quantitative
      measures of AD progression.
AB  - BDNF is a functional candidate gene for AD, owing to its role in neuronal
      development and survival. The Val66Met (G196A), along with another C270T
      polymorphism has been associated with AD, however, the effects seem to be
      inconsistent across studies. We examined the association of the G196A and C270T
      polymorphisms with sporadic late-onset AD (LOAD) in a large American White cohort
      of 995 AD cases and 671 controls and an American Black cohort of 64 AD cases and
      45 controls. We also examined the association of these polymorphisms with
      quantitative measures of AD progression, including age at onset (AAO), disease
      duration and Mini-Mental State Examination (MMSE) scores. No significant
      difference in allele, genotype or estimated haplotype frequencies was observed
      between AD cases and controls within the American White and Black cohorts for the
      G196A and C270T polymorphisms. However, the frequency of the 196*A allele was
      significantly lower in American Black subjects compared to Whites. While MMSE
      scores were significantly lower in C270T/CT carriers compared to C270T/CC
      subjects only among American Blacks, no such effect was observed among American
      Whites. The BDNF polymorphisms did not affect AAO or disease duration measures in
      American Whites or Blacks. Our finding does not support any association between
      the BDNF/G196A or C270T polymorphism and the risk of sporadic LOAD among American
      Whites or Blacks. The significant effect of the C270T polymorphism observed on
      MMSE scores among American Blacks needs to be further explored in a larger
      cohort.

PMID- 15843070
TI  - Recent advances on autosomal dominant nocturnal frontal lobe epilepsy:
      "understanding the nicotinic acetylcholine receptor (nAChR)".
AB  - Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is characterized by
      clusters of nocturnal motor seizures, which are often stereotyped and brief. They
      vary from simple arousals during sleep to dramatic, bizarre, hyperkinetic events
      with tonic or dystonic features. A minority of patients may experience aura. This
      disease is caused by various mutations of genes coding for subunits of neuronal
      acetylcholine receptor comprising the sodium/potassium ion channel. Recent
      advances in molecular genetics have provided the means for a better understanding
      of human epileptogenesis at a molecular level, which can facilitate clinical
      diagnosis and provides a more rational basis of therapy of this form of epilepsy.
      In this review, we report the recent data in the genetics of ADNFLE.

PMID- 15843071
TI  - Profile of fisting in term newborns.
AB  - BACKGROUND: Persistence of fisting of hands and cortical thumb is a predictor of
      abnormalities in development and dysfunction of the central nervous system,
      though this may be a normal finding in the immediate newborn period. AIM: To
      study the profile of fisting in early neonatal period. METHODS: Five hundred and
      fifty healthy term neonates were studied. Hand position was examined by a single
      observer between 24-48h of birth when the baby was awake and quiet. Complete
      fisting was defined as flexed fingers covering both proximal and distal palmer
      creases. If only the distal crease was covered, it was defined as incomplete
      fisting. Thumb position was observed as thumb by the side of the fingers, under
      the fingers and above the fingers. RESULTS: Of the total 550 babies, 338 (61.45%)
      had bilateral, 39 (7.09%) had right sided and 38 (6.91%) had left sided fisting
      and 135 (24.55%) had open hands. Of the 1100 hands, 669 hands (60.8%) had
      complete and 84 (7.63%) had incomplete fisting. "Cortical thumb" was found in 57%
      of fisted hands. There was no significant difference (p>0.05) in fisting
      according to the sex and weight of the babies. CONCLUSION: Fisting was a
      predominant hand posture among the babies (75.45%) but cortical thumb with
      bilateral fisting was seen in only 30% of babies.

PMID- 15843072
TI  - Precocity of the acquisition of language and type II spinal muscular atrophy in 3
      4-year-old children: a study of 12 cases.
AB  - We studied the development of language in 3-4-year-old children with type II
      spinal muscular atrophy (SMA) (10 boys and two girls), aged 36-47 months (mean
      age 39.83+/-4.68 months) and compared our findings to a control group of 26
      healthy children (mean age 40.00+/-4.43 months, 22 boys and four girls). We
      carried out a lexicogrammatical analysis of the data and we observed significant
      differences in the "vocabulary", "nouns", "verbs", "words" and "adverbs"
      variables between the children with SMA and the controls. Three- to four-year-old
      children suffering from type II spinal muscular atrophy, an autosomal genetic
      disease causing severe physical handicap (motor, functional, respiratory),
      presented a higher level of lexical and semantic development than the controls,
      demonstrating the precocity of development of morphosyntax in these children.

PMID- 15843073
TI  - Pancreatitis, complicated by a pancreatic pseudocyst associated with the use of
      valproic acid.
AB  - A 12-year-old boy developed pancreatitis, complicated by a pancreatic pseudocyst,
      as an adverse reaction to valproic acid (VPA) treatment for epilepsy.
      Pancreatitis subsided within three weeks after discontinuation of VPA. The
      pancreatic pseudocyst was managed without surgery and resolved spontaneously in
      four weeks. Valproic acid was concluded to be the most probable cause, since no
      other explanation was found. According to the literature VPA is a rare but known
      cause of pancreatitis. A computer-assisted literature search revealed seven
      previously reported cases of VPA-induced pancreatitis complicated by a pancreatic
      pseudocyst. Six of these patients were under 20 years of age. Four patients were
      treated conservatively; three needed cystostomy or external drainage. All
      patients recovered. Patients using VPA, especially children, presenting with
      acute abdominal pain should be suspected of valproic acid-induced pancreatitis.
      If VPA induced pancreatitis is complicated by a pseudocyst, conservative
      treatment should be the first line of treatment.

PMID- 15843074
TI  - Pseudocystic cryptococcal meningitis complicated by transient periaqueductal
      obstruction in a child with HIV infection.
AB  - We describe a 10-year-old human immune deficiency virus (HIV) infected girl who
      presented with pseudocystic cryptococcal meningitis complicated by hydrocephalus
      secondary to aqueductal obstruction. The neuroradiological features of this case
      are presented and we also postulate on the pathogenesis of the type of
      hydrocephalus encountered.

PMID- 15843075
TI  - Peripheral neuropathy--a novel finding in dyskeratosis congenita.
AB  - We report the case of a 3.5-year-old boy who presented with truncal ataxia,
      microcephaly and delayed global development in infancy. Hypoplasia of cerebellum
      and corpus callosum and delayed myelination were found on brain MRI. Failure to
      thrive, sparse hairs and dystrophic nails became evident at the age of 2 years.
      He subsequently developed bleeding tendency, thrombocytopenia and hypocellularity
      on bone marrow examination leading to a diagnosis of dyskeratosis congenita.
      Impaired pain perception with slowing of nerve conduction velocities was
      demonstrated, suggesting a mild peripheral neuropathy. To the best of our
      knowledge, peripheral neuropathy has never been reported as a feature of the
      congenital form of dyskeratosis congenita.

PMID- 15843076
TI  - Clinical and genetic aspects of idiopathic epilepsies in childhood.
AB  - The identification of the first genes associated with idiopathic epilepsy has
      been an important breakthrough in the field of epilepsy research. In almost all
      cases these genes were found to encode components of voltage- or ligand-gated ion
      channels or functionally related structures. For many other idiopathic syndromes,
      there is linkage evidence to one or more chromosomes, but the genes have not yet
      been identified. Identification of the responsible genes and their gene products
      will further increase the knowledge of the pathogenic mechanisms involved in
      epilepsy, and will hopefully facilitate the development of drug targets for the
      effective treatment of epilepsy. This review gives an overview of the clinical
      characteristics and an update of genetic research of those idiopathic childhood
      epilepsies for which genes have been identified and the monogenic idiopathic
      childhood epilepsies for which mapping data are available.

PMID- 15843077
TI  - Helicobacter pylori infection and ischaemic heart disease: an overview of the
      general literature.
AB  - In the last years, a considerable number of studies have been performed on the
      correlation between Helicobacter pylori infection and ischaemic heart disease.
      The reason is the supposed role of some chronic infections in the genesis and
      development of vessel wall injury and atheromatous plaque, as already reported
      for Chlamydia pneumoniae and herpes viruses. While this association may be
      theoretically conceivable, it still remains debated from a practical point of
      view. Epidemiological and animal studies as well as some eradicating trials gave
      conflicting results, while studies investigating the specific molecular mimicry
      mechanisms induced by H. pylori strongly support the association. Moreover, none
      of the studies performed so far did take into account the effect of the genetic
      susceptibility to develop ischaemic heart disease or to respond to H. pylori
      infection. In particular, while the exposure to some known risk factor for
      atherosclerosis should lead to develop ischaemic heart disease, no condition or
      exposure, either individual or in combination, completely explains the occurrence
      and the progression of the disease, as many patients develop ischaemic heart
      disease in the absence of any risk factor. Based on these concepts, can we state
      that H. pylori infection may cause the same effect in patients with ischaemic
      heart disease as in healthy subjects? Further studies are needed in order to
      clarify this issue.

PMID- 15843078
TI  - Paediatric endoscopy: important progress and minor limitations.

PMID- 15843080
TI  - Rifaximin in patients with lactose intolerance.
AB  - BACKGROUND: Abdominal symptoms linked to lactose malabsorption may be caused by
      metabolic activity of colonic bacteria. Rifaximin, a non-absorbable rifampycin
      derivative, is active against colonic bacteria, it may be useful in the treatment
      of lactose intolerance. AIM: The aim of this study has been to evaluate short
      term rifaximin therapy in patients with lactose intolerance. METHODS: Thirty-two
      patients with lactose intolerance diagnosed using the hydrogen lactose breath
      test were studied. Fourteen patients received rifaximin 800 mg/day for 10 days,
      13 patients followed a diet without milk for 40 days and 5 patients received a
      placebo for 10 days. Total breath H(2) excretion expressed as area under the
      curve, and the symptom score were evaluated in all patients at the start, and
      subsequently after 10 and 40 days. RESULTS: In the 14 patients who received
      rifaximin for 10 days, area under the curve at day 10 and day 40 was
      statistically significantly lower than the one computed at basal (P<0.01). Diet
      reduced area under the curve progressively reaching statistical significance at
      day 40, while the placebo did not change area under the curve throughout the
      study. The total symptom score significantly improved after rifaximin and diet.
      CONCLUSION: In patients with lactose intolerance, a 10-day therapy with rifaximin
      as well as 40-day diet without lactose reduces the area under the curve and the
      symptom score.

PMID- 15843079
TI  - Idiopathic achalasia is not allelic to alacrima achalasia adrenal insufficiency
      syndrome at the ALADIN locus.
AB  - BACKGROUND: Evidence indicates that patients with familial achalasia associated
      with Allgrove or triple-A syndrome (i.e. alacrima, achalasia and
      adrenocorticotropin-resistant adrenal insufficiency with neurological impairment)
      have mutations of the alacrima achalasia adrenal insufficiency syndrome (AAAS)
      gene. AIM: The present study was aimed at identifying possible AAAS gene
      mutations in patients with established idiopathic non-familial achalasia.
      METHODS: Genomic DNA of 41 patients was isolated from peripheral blood cells
      using standard methods. The 16 exons of the AAAS gene (or ALADIN) were screened
      for mutations using the denaturing high-performance liquid chromatography method.
      RESULTS: Four heterozygous nucleotidic variations have been identified in
      patients with idiopathic achalasia, among which three were exonic conservative
      polymorphisms [i.e. D138D (GAT-->GAC), L227L (TTG-->CTG) and F285F (TTC-->TTT) in
      exons 5, 7 and 9, respectively]. The fourth nucleotidic variation was located in
      intron 13 (IVS14-23delT). All variants have been regarded as polymorphisms
      resulting in a normal ALADIN protein since they are either conservative or lying
      outside the consensus splice sites. CONCLUSIONS: Our data do not support a
      pathogenetic role for common AAAS gene mutations in patients with idiopathic
      achalasia as seen in Allgrove syndrome. These findings suggest the participation
      of different mechanisms in the pathogenesis of idiopathic achalasia.

PMID- 15843081
TI  - Effects of Lactobacillus GG on genes expression pattern in small bowel mucosa.
AB  - BACKGROUND AND AIMS: Probiotics have been used for cure and prevention of several
      clinical conditions. However, further insights into the mechanism of action are
      needed to understand the rationale of their use. The aim of this study was to
      investigate the influence of Lactobacillus GG on the genetic expression patterns
      in the small bowel mucosa. METHODS: Six male patients (38+/-5 years) with
      endoscopically proven oesophagitis were enrolled. All patients were treated for 1
      month with esomeprazole and randomised to receive Lactobacillus GG or placebo.
      After 1 month of treatment, upper endoscopy was repeated. Biopsies of the
      duodenal mucosa were taken prior to and after the treatment, and the genes
      expression patterns were assessed using GeneChip Human U133A array. Genes with
      significant expression changes were selected and analysed to identify specific
      cellular pathways modified by Lactobacillus GG. To support the array data, 10
      target genes were studied using Syber-Green PCR. RESULTS: Microarray analysis
      showed that Lactobacillus GG administration determined the up- and down
      regulation of 334 and 92 genes, respectively. Real-time PCR confirmed the
      reliability of the analysis. Lactobacillus GG mainly affected the expression of
      genes involved in immune response and inflammation (TGF-beta and TNF family
      members, cytokines, nitric oxide synthase 1, defensin alpha 1), apoptosis, cell
      growth and cell differentiation (cyclins and caspases, oncogenes), cell-cell
      signalling (ICAMs and integrins), cell adhesion (cadherins), signal transcription
      and transduction. CONCLUSIONS: These data indicate that administration of
      Lactobacillus GG is associated with a complex genetic response of the duodenal
      mucosa, reflected by the up- and down-regulation of several genes involved in
      specific cellular pathways.

PMID- 15843082
TI  - A functional interleukin-10 mutation in Dutch patients with Crohn's disease.
AB  - BACKGROUND AND AIMS: Interleukin-10 is an anti-inflammatory and immunomodulatory
      cytokine. Interleukin-10 deficient mice are prone to develop chronic colitis.
      Administration of recombinant human interleukin-10 has been proposed to have a
      beneficial effect in a subgroup of patients with Crohn's disease. Recently, we
      found an interleukin-10 Gly15Arg mutation in a family with Crohn's disease which
      is associated with reduced interleukin-10 secretion by in vitro stimulated
      monocytes and lymphocytes. We hypothesised that this interleukin-10 mutation
      plays a role in maintaining the inflammatory process in Crohn's disease in some
      families. PATIENTS AND METHODS: We evaluated interleukin-10 Gly15Arg in 379
      patients with Crohn's disease, and 75 unrelated healthy controls. Also, first
      degree family members of interleukin-10 Gly15Arg carriers were evaluated.
      Additionally, mutation carriers and their relatives were evaluated for CARD15
      R702W, G908R, and 1007fs. RESULTS: Two patients with Crohn's disease were
      heterozygous for the interleukin-10 Gly15Arg mutation. No homozygotes were found.
      The Gly15Arg mutation was not observed in the controls. In first degree family
      members of the Crohn's disease-affected interleukin-10 Gly15Arg carriers, the
      mutation was found in Crohn's disease-affected as well as in their apparently
      healthy individuals. All family members carried one or two CARD15 mutation(s).
      CONCLUSION: The interleukin-10 Gly15Arg mutation is rare in patients with Crohn's
      disease, and is not associated with the disease in the Netherlands.

PMID- 15843083
TI  - Interferon treatment in children with chronic hepatitis C: long-lasting remission
      in responders, and risk for disease progression in non-responders.
AB  - BACKGROUND AND AIM: Large interferon-based therapeutic trials are still lacking
      in children with hepatitis C and the long-term safety and efficacy of interferon
      is unknown. This study describes the outcome of hepatitis C in 43 children
      enrolled in an open-label interferon trial, and were followed up to 66 months
      after stopping treatment. PATIENTS AND METHODS: All patients received interferon
      alfa2a (5MU/m(2)) thrice weekly for 6 months; children with genotype 1b received
      3MU/m(2) thrice weekly for 6 additional months. RESULTS: Nine children
      discontinued interferon for adverse events and three were not compliant to
      treatment. Eight (19%, intention to treat analysis), including 2/20 (10%) with
      genotype 1b and 6/12 (50%) with genotypes 2 or 3, were sustained responders 12
      months after stopping therapy. During further follow-up (mean+/-S.D.: 44.7+/-14.6
      months), response was maintained; two non-responders cleared viremia, while a
      young boy progressed to cirrhosis. CONCLUSIONS: Small sample size and therapy
      withdrawal are the major limitations in the interpretation of our results.
      Nevertheless, our data, suggesting that response to interferon in children with
      hepatitis C is genotype-related and stable, agree with the results of large
      studies in adults. The outcome in non-responders was variable, including
      persistence of viremia and mild-moderate cytolysis (most cases), progression to
      cirrhosis, or eventual sustained viremia clearance.

PMID- 15843084
TI  - Effect of cyanidin 3-O-beta-glucopyranoside on hepatic stellate cell
      proliferation and collagen synthesis induced by oxidative stress.
AB  - BACKGROUND: Reactive oxygen species play a role in the pathogenesis of hepatic
      fibrosis, mainly through the activation of hepatic stellate cells. Cyanidin-3-O
      beta-glucopyranoside is a natural antioxidant compound distributed in several
      fruits and vegetables. AIM: To evaluate the effect of cyanidin-3-O-beta
      glucopyranoside on hepatic stellate cells proliferation and collagen synthesis
      induced by a pro-oxidant agent. METHODS/RESULTS: Oxidative stress was induced by
      incubation of hepatic stellate cells with a ferric nitrilotriacetate complex (100
      micromol/L). Incubation with ferric nitrilotriacetate induced an increased
      intracellular hydroperoxide formation, which was completely inhibited by cyanidin
      3-O-beta-glucopyranoside at a concentration of 50mumol/L. Similarly, cyanidin-3-O
      beta-glucopyranoside was able to inhibit ferric nitrilotriacetate-induced hepatic
      stellate cells proliferation, evaluated by an ELISA method, with a maximal effect
      at 50mumol/L. Incubation of hepatic stellate cells with cyanidin-3-O-beta
      glucopyranoside inhibited ferric nitrilotriacetate-induced extracellular signal
      regulated kinase 1/2 activation, evaluated by western blot, whereas it did not
      affect p70S6 kinase and AKT expression. Finally, cyanidin-3-O-beta
      glucopyranoside reduced ferric nitrilotriacetate-induced Na(+)/H(+) exchange
      activation, evaluated by a spectrofluorimetric method, and collagen type I
      synthesis, evaluated by northern blot. CONCLUSION: Cyanidin-3-O-beta
      glucopyranoside is able to modulate hepatic stellate cells proliferation and type
      I collagen synthesis induced by a pro-oxidant agent, thus suggesting a potential
      role for this antioxidant compound in the prevention of fibrosis in chronic liver
      diseases.

PMID- 15843085
TI  - Alpha-SMA expression in hepatic stellate cells and quantitative analysis of
      hepatic fibrosis in cirrhosis and in recurrent chronic hepatitis after liver
      transplantation.
AB  - BACKGROUND: The alpha isotype of actin expressed by hepatic stellate cells
      reflects their activation to myofibroblast-like cell and has been directly
      related to experimental liver fibrogenesis, and indirectly to human fibrosis in
      chronic liver disease. AIMS: To evaluate the changes in distribution and
      percentage of alpha-smooth muscle actin-positive hepatic stellate cells and the
      correlation with the degree of the fibrosis in cirrhotic livers, as well as in
      patients with recurrent HCV chronic hepatitis after liver transplantation.
      METHODS: Human liver biopsies were divided in four groups: (1) normal livers
      obtained from cadaveric liver donors (n=35), (2) cirrhosis post-HBV hepatitis
      (n=11), (3) cirrhosis post-HCV hepatitis (n=10), and (4) post-transplant
      recurrent HCV chronic hepatitis (n=13). Samples were stained with anti-alpha
      smooth muscle actin antibody by immunoperoxidase method and semi-quantitatively
      evaluated. Liver fibrosis was assessed from specimens stained with Masson's
      trichrome and quantified by computer image analysis. RESULTS: The percentage of
      alpha-smooth muscle actin-positive hepatic stellate cells was significantly
      higher in the HBV cirrhosis, HCV cirrhosis and post-transplant HCV recurrent
      hepatitis groups (36.1+/-15.2, 23.8+/-19.7 and 27.8+/-16.4%, respectively)
      compared to the liver donor group (2.9+/-4.0%). The alpha-smooth muscle actin
      positive hepatic stellate cells to fibrous tissue ratio were significantly higher
      in the post-transplant recurrent HCV hepatitis group (2.36+/-1.12) compared to
      both the donor livers and the HCV cirrhosis groups (0.74+/-1.09 and 1.03+/-0.91,
      respectively). The alpha-smooth muscle actin-positive hepatic stellate cell
      percentage and fibrosis correlated positively in the post-transplant recurrent
      HCV hepatitis group and negatively in the HCV cirrhosis group. No difference in
      the immunohistochemical and morphometrical variables was found between the HCV
      cirrhosis and HBV cirrhosis groups. CONCLUSIONS: These results indirectly confirm
      that, in vivo, alpha-smooth muscle actin expression is a reliable marker of
      hepatic stellate cells activation which precedes fibrous tissue deposition even
      in the setting of recurrent HCV chronic hepatitis after liver transplantation,
      and it could be useful to identify the earliest stages of hepatic fibrosis and
      monitoring the efficacy of the therapy. In the presence of advanced cirrhosis
      other factors, rather than alpha-smooth muscle actin-positive hepatic stellate
      cells, may sustain fibrosis deposition.

PMID- 15843086
TI  - Therapeutic ERCP in paediatric patients.
AB  - BACKGROUND: Major limitations of endoscopic retrograde cholangiopancreatography
      in paediatric populations are a low incidence of biliopancreatic disease among
      children, the equipment dimensions (size of endoscopes and devices) and the
      increasing role of MR-cholangiopancreatography in the field of diagnostic
      indications. Aim of this study was to evaluate the diagnostic and therapeutic
      yields of endoscopic retrograde cholangiopancreatography for biliopancreatic
      diseases in a paediatric population. METHODS: Between 1996 and 2002, 48
      endoscopic retrograde cholangiopancreatographies were performed in 38 children
      aged 4 weeks to 17 years as part of the diagnostic evaluation for suspected
      pancreatic or biliary tract disease. Endoscopic retrograde
      cholangiopancreatography was carried out under general anaesthesia, using
      prototype paediatric duodenoscopes or standard duodenoscopes in children younger
      or older than 18 months, respectively. RESULTS: The indications to perform
      endoscopic retrograde cholangiopancreatography were common bile duct stones (14
      children), biliopancreatic abnormalities (8), primary sclerosing cholangitis (2),
      Wirsung disruption (1), biliary leakage (1), cholestasis (4) and pancreatitis
      (8). Cannulation was successful in all patients but one. Sphincterotomy together
      with stone extraction or stent insertion was performed in 30/38 patients.
      Immediate complications were mild and treated conservatively. CONCLUSIONS:
      Diagnostic and therapeutic endoscopic retrograde cholangiopancreatography can be
      used safely and effectively in the management of biliopancreatic diseases in
      childhood as well. Indications, endoscopic techniques and complications are
      similar to those reported for adult patients.

PMID- 15843087
TI  - Origin of the long common channel based on pancreatographic findings in
      pancreaticobiliary maljunction.
AB  - BACKGROUND AND AIMS: The origin of a long common channel in pancreaticobiliary
      maljunction was suggested to be the ventral pancreatic duct. Pathogenesis of long
      common channels was investigated by anatomically analysing the arrangement of
      pancreatic ducts in pancreaticobiliary maljunction. MATERIALS AND METHODS:
      Cholangiopancreatography was performed for 66 cases of pancreaticobiliary
      maljunction and 200 controls. The accessory pancreatic duct was classified
      according to course and shape. In cases with long- or short-type accessory
      pancreatic duct, lengths of the main pancreatic duct from orifice to first
      inferior branch and junction with the accessory pancreatic duct, and the common
      channel were measured. RESULTS: Lengths of the main pancreatic duct from orifice
      to first inferior branch or junction with the accessory pancreatic duct were
      significantly longer in cases of pancreaticobiliary maljunction cases with the
      long- or short-type accessory pancreatic duct than in controls (p<0.01). Lengths
      of the main pancreatic duct from first inferior branch to junction with the
      accessory pancreatic duct were roughly equivalent in pancreaticobiliary
      maljunction and controls. CONCLUSIONS: Long common channels in pancreaticobiliary
      maljunction might be formed embryologically with adhesion of the right ventral
      pancreatic duct and the terminal portion of the bile duct.

PMID- 15843088
TI  - Gastric involvement in a patient with secondary syphilis.
AB  - A 30-year-old man was referred because of a short lasting history of severe
      epigastric pain and early satiety, with remarkable weight loss. Physical
      examination was fully consistent with secondary syphilis and upper GI tract
      endoscopy revealed multiple gastric mucopurulent erosions and several nodular
      lesions ranging from 2 to 3 cm in diameter, with central crater, abruptly ending
      at the pyloric level. Appropriate antibiotic treatment obtained a dramatic
      improvement and complete reversal of cutaneous and gastric lesions.

PMID- 15843089
TI  - Ischemic colitis associated with rofecoxib.
AB  - Rofecoxib is a selective cyclooxygenase-2 inhibitor that has been approved for
      the treatment of osteoarthritis and management of acute pain. Recent debate has
      emerged regarding the prothrombotic potential and the cardiovascular safety of
      this new drug, especially at doses greater than 25mg. We describe two extensively
      investigated cases of self-limited ischemic colitis in patients who were briefly
      treated with 50mg rofecoxib daily for acute pain. In both cases, the onset of
      symptoms correlated temporally with rofecoxib use and symptoms abated with drug
      discontinuation. There was no evidence of other possible causes of colon
      ischemia. A causal relationship between the start of rofecoxib treatment and the
      colon ischemia cannot be definitely established on the basis of the evidence, but
      the temporal relationship is striking and the pathophysiological rationale could
      be founded.

PMID- 15843090
TI  - Randomised clinical trials 30 years later: a matter of clinical equipoise?

PMID- 15843091
TI  - Telomerase: regulation, function and transformation.
AB  - Work from several laboratories over the past decade indicates that the
      acquisition of constitutive telomerase expression is a critical step during the
      malignant transformation of human cells. Normal human cells transiently express
      low levels of telomerase, the ribonucleoprotein responsible for extending and
      maintaining telomeres, and exhibit telomere shortening after extended passage,
      whereas most cancers exhibit constitutive telomerase expression and maintain
      telomeres at stable lengths. These observations establish a direct connection
      between immortalization and stabilization of telomere structure. However, recent
      work suggests that telomerase also contributes to cancer development beyond its
      role in maintaining stable telomere lengths. In this review, we summarize recent
      observations that support the concept that telomerase plays multiple roles in
      facilitating human cell transformation.

PMID- 15843093
TI  - Multi-dysfunctional pathophysiology in ITP.
AB  - Idiopathic thrombocytopenic purpura (ITP) is an organ-specific autoimmune
      disorder characterized by a low platelet count and mucocutaneous bleeding. The
      decrease of platelets is caused by increased autoantibodies against self
      antigens, particularly IgG antibodies against GPIIb/IIIa. The production of these
      autoantibodies by B cells depends on a number of cellular mechanisms that form a
      network of modulation, with T cells playing a pivotal role in pathophysiology.
      Delineation of the dysfunction of cellular immunity has recently been attempted.
      This review will focus on these recent advances applicable to ITP and to
      highlight how these may translate into novel approaches to treatment in the
      future. Multi-dysfunction in these networks may include a failure of self-antigen
      recognition and tolerance, involvement of abnormal cell surface molecules,
      altered Th1/Th2 cytokine profiles, impaired megakaryocytopoiesis and impaired
      cell-mediated cytotoxicity. In ITP, multi-step dysfunctions in these networks may
      take place that finally lead to the occurrence of the disease. Therefore,
      unveiling these dysfunctions is vital in understanding the pathophysiology of ITP
      and will finally lead to the development of new therapies to fight the disease.

PMID- 15843092
TI  - Gene expression arrays in cancer research: methods and applications.
AB  - During the last 5 years, the number of papers describing data obtained by
      microarray technology increased exponentially with about 3000 papers in 2003.
      Undoubtedly, cancer is by far the disease that received most of the attention as
      far as the amount of data generated. As array technology is rather new and highly
      dependent on bioinformatics, mathematics and statistics, a clear understanding of
      the knowledge and information derived from array-based experiments is not widely
      appreciated. We shall review herein some of the issues related to the
      construction of DNA arrays, quantities and heterogeneity of probes and targets,
      the consequences of the physical characteristics of the probes, data extraction
      and data analysis as well as the applications of array technology. Our goal is to
      bring to the general audience, some of the basics of array technology and its
      possible application in oncology. By discussing some of the basic aspects of the
      methodology, we hope to stimulate criticism concerning the conclusions proposed
      by authors, especially in the light of the very low degree of reproducibility
      already proven when commercially available platforms were compared . Regardless
      of its pitfalls, it is unquestionable that array technology will have a great
      impact in the management of cancer and its applications will range from the
      discovery of new drug targets, new molecular tools for diagnosis and prognosis as
      well as for a tailored treatment that will take into account the molecular
      determinants of a given tumor. Hence, we shall also highlight some of the already
      available and promising applications of array technology on the day-to-day
      practice of oncology.

PMID- 15843094
TI  - Socio-economic factors and health care system characteristics related to cancer
      survival in the elderly. A population-based analysis in 16 European countries
      (ELDCARE project).
AB  - The ELDCARE study aims to investigate, at the ecological level, the relationships
      between socio-economic variables and cancer survival in patients aged 65 years
      and over. Survival data for patients diagnosed during the period 1985-1989 and
      followed up to 1994 were provided by 43 European Cancer Registries in 16
      countries participating in the EUROCARE 2 project. Relative survival was computed
      by Hakulinen's methods. Data on socio-economic factors were collected by national
      statistics offices for the years around 1991. Pearson's correlation was used to
      study the relationships between cancer survival and socio-economic factors. We
      selected four groups of variables. The first group included macro-economic
      variables (such as Gross Domestic Product, GDP; Total Health Expenditure, THE);
      the second, the main characteristics of national health care systems; the third,
      demographic factors; and the fourth, variables on labour market organisation. The
      countries with the largest proportions of elderly populations, in Northern and
      Western Europe, spent more on health than the less affluent countries of Eastern
      Europe. GDP was strongly related to THE but a very high variability in Computed
      Tomography Scanners (CTS) among countries with similar THE was observed. Indeed,
      those countries with THE around US 1500 dollars per capita had survival rates for
      breast cancer ranging from 67 to 82%. Cancer survival in elderly patients in
      Europe was most strongly related to GDP and THE, especially for good prognosis
      cancers. Survival was strongly correlated with health care technologies,
      particularly CTS, but not with health employment. Survival was positively
      correlated with proportion of married elderly people (and negatively with widowed
      elderly), suggesting a role played by social support in influencing the prognosis
      of elderly patients. These results highlight how health outcomes in the elderly
      are a complex phenomenon, not determined only by GDP and THE, but affected by
      social organisation and life habits as well as economic development conditions.

PMID- 15843095
TI  - The abbreviated comprehensive geriatric assessment (aCGA): a retrospective
      analysis.
AB  - BACKGROUND: A comprehensive geriatric assessment (CGA) is a multidimensional
      assessment that is designed to detect health problems. A barrier to conducting
      the CGA is the length of time required to complete the entire assessment.
      OBJECTIVE: To understand what items contained in the instruments that make up the
      CGA could be compiled to construct an abbreviated CGA (aCGA). DESIGN/SETTING: A
      retrospective chart review of patients at the H. Lee Moffitt Cancer Center.
      PARTICIPANTS: Over 500 charts between 1995 and 2001 were reviewed on patients 70
      and over. MEASUREMENTS: Item-to-total correlations and Cronbach's alpha
      coefficient were calculated. Construct validity was assessed using a Pearson's
      product moment correlation coefficient. RESULTS: Fifteen items were compiled to
      form the aCGA. Cronbach's alpha was 0.65-0.92 on each instrument of the entire
      CGA compared to 0.70-0.94 on the aCGA. Correlations ranged from 0.84 to 0.96 for
      the entire CGA and the aCGA. CONCLUSION: An aCGA can be helpful in screening for
      those seniors who would benefit from the entire CGA.

PMID- 15843096
TI  - Pilot testing of the computerized cognitive test Microcog in chemotherapy-treated
      older cancer patients.
AB  - BACKGROUND: Chemotherapy has a potential for inducing cognitive side effects.
      However, no study has focused on elderly cancer patients, a group that might be
      at risk for this complication. Computerized cognitive tests are available and
      could simplify cooperative group studies on the matter, but have not been applied
      to older cancer patients. METHODS: We tested the performance of Microcog (short
      form) in a sample of 10 consecutive cancer patients, aged 70 and older, having
      received chemotherapy. Patients were also asked by questionnaire to express their
      comments on the test. RESULTS: Six patients had never used a computer. All
      reported at least minor visual impairment. All did complete the test without
      pause. Nine out of 10 thought that most patients like them would have no problems
      completing the test. As a group, our patient sample generally performed within
      normal limits for age and education. There were a wide range of scores for the
      majority of the subscales, with the greatest variability of scores in Spatial
      Processing and Information Processing Accuracy and the least variability in
      reaction time. The results were robust when assessed by level of computer
      literacy, minor auditory and visual problems, and fluent English as a second
      language. CONCLUSIONS: A computer test such as Microcog appears well feasible in
      older cancer patients. It appears robust to comorbidity. This bodes well for a
      potential use of such tests in trials conducted in this patient population.

PMID- 15843097
TI  - Treatment of stage IV colorectal carcinoma in elderly patients.
AB  - Colorectal adenocarcinoma ranks second as a cause of death due to cancer in the
      Western world. In Europe, 40% of patients with colorectal cancer are over 70
      years old and the incidence increased through the 1980's. Without any treatment
      the median survival after the detection of liver metastases is approximately 9
      months, depending on the extent of disease at the time of diagnosis but not on
      the patients age. In the elderly there are only few data apt to define the
      standard regimen in the advanced disease, but results seem similar to those
      observed in younger patients. As a result of exclusion criteria and screening,
      elderly patients entering clinical trials are usually a select group, with good
      performance status, access to transportation, and limiting numbers of coexisting
      conditions. This paper examines the factors pertinent to the small number of
      clinical trials designed for metastatic colorectal cancer in this group of
      persons.

PMID- 15843098
TI  - Treatment of pain in older patients.
AB  - Pain in older adults is a highly prevalent problem. While the basis of pain
      management in older individuals is similar to that for younger patients, it may
      differ in terms of presentation, assessment, and management. This article
      explores the basic concepts of pain control with a focus on older patients with
      cancer and highlights issues clinicians should consider when treating these
      individuals.

PMID- 15843099
TI  - The neuropsychology of autistic spectrum disorders.

PMID- 15843100
TI  - Early regression in social communication in autism spectrum disorders: a CPEA
      Study.
AB  - In a multisite study of 351 children with autism spectrum disorders, 21 children
      with developmental delays, and 31 children with typical development, this study
      used caregiver interviews (i.e., the Autism Diagnostic Interview-Revised) at the
      time of entry into other research projects and follow-up telephone interviews
      designed for this project to describe the children's early acquisition and loss
      of social-communication milestones. Children who had used words spontaneously and
      meaningfully and then stopped talking were described by their caregivers as
      showing more gestures, greater participation in social games, and better
      receptive language before the loss and fewer of these skills after the loss than
      other children with autism spectrum disorders. A significant minority of children
      with autism without word loss showed a very similar pattern of loss of social
      communication skills, a pattern not observed in the children with developmental
      delays or typical development.

PMID- 15843101
TI  - Source memory in children with autism spectrum disorders.
AB  - The evidence to date regarding memory processes in children with autism spectrum
      disorders (ASD) remains equivocal. Although children with these
      neurodevelopmental disorders have been shown to display exceptional memories for
      fact-based information, they seem to be less able to attach meaning or context to
      their memories. Thus, this study investigated the specific role of source memory
      in autism. Children with ASD were compared to a chronological and mental age
      matched comparison group of typically developing children. Although children with
      autism performed similarly to controls on a fact recognition measure, their
      performance on a source memory task was significantly lower. The findings
      indicated, however, that the nature of source memory confusion in children with
      autism does not appear to reflect a generalized deficit in attaching context to
      memories but rather is dependent on the specific to-be-remembered information
      that, in this study, involves social aspects of context.

PMID- 15843102
TI  - Executive dysfunction and its relation to language ability in verbal school-age
      children with autism.
AB  - This study examined executive dysfunction and its relation to language ability in
      verbal school-age children with autism. Participants were 37 children with autism
      and 31 nonautistic comparison participants who were matched on age and on verbal
      and nonverbal IQ but not on language ability, which was lower in the autism
      group. Children with autism exhibited deficits compared to the comparison group
      across all 3 domains of executive function that were assessed including working
      memory (Block Span Backward; Isaacs & Vargha-Khadem, 1989), working memory and
      inhibitory control (NEPSY Knock-Tap; Korkman, Kirk, & Kemp, 1998), and planning
      (NEPSY Tower; Korkman et al., 1998). Children with autism were less developed
      than the comparison group in their language skills, but correlational analyses
      revealed no specific association between language ability and executive
      performance in the autism group. In contrast, executive performance was
      positively correlated with language ability in the comparison group. This pattern
      of findings suggest that executive dysfunction in autism is not directly related
      to language impairment per se but rather involves an executive failure to use of
      language for self-regulation.

PMID- 15843103
TI  - Executive functions in autism and Asperger's disorder: flexibility, fluency, and
      inhibition.
AB  - The Color-Word Interference Test, Trail Making Test, Verbal Fluency Test, and
      Design Fluency Test from the Delis-Kaplan Executive Function System (Delis,
      Kaplan, & Kramer, 2001) were administered to 12 high-functioning adults and
      adolescents with autistic disorder or Asperger's disorder. Each test included a
      switching condition in addition to baseline and/or other executive-function
      conditions. Participants performed significantly below average on a composite
      measure of executive functioning adjusted for baseline cognitive ability. Complex
      verbal tasks that required cognitive switching and initiation of efficient
      lexical retrieval strategies produced the most consistent deficits, whereas
      cognitive inhibition was intact. We discuss implications of these findings for
      understanding the neurocognitive substrates of autistic spectrum disorders.

PMID- 15843104
TI  - Understanding the nature of face processing impairment in autism: insights from
      behavioral and electrophysiological studies.
AB  - This article reviews behavioral and electrophysiological studies of face
      processing and discusses hypotheses for understanding the nature of face
      processing impairments in autism. Based on results of behavioral studies, this
      study demonstrates that individuals with autism have impaired face discrimination
      and recognition and use atypical strategies for processing faces characterized by
      reduced attention to the eyes and piecemeal rather than configural strategies.
      Based on results of electrophysiological studies, this article concludes that
      face processing impairments are present early in autism, by 3 years of age. Such
      studies have detected abnormalities in both early (N170 reflecting structural
      encoding) and late (NC reflecting recognition memory) stages of face processing.
      Event-related potential studies of young children and adults with autism have
      found slower speed of processing of faces, a failure to show the expected speed
      advantage of processing faces versus nonface stimuli, and atypical scalp
      topography suggesting abnormal cortical specialization for face processing. Other
      electrophysiological studies have suggested that autism is associated with early
      and late stage processing impairments of facial expressions of emotion (fear) and
      decreased perceptual binding as reflected in reduced gamma during face
      processing. This article describes two types of hypotheses-cognitive/perceptual
      and motivational/affective--that offer frameworks for understanding the nature of
      face processing impairments in autism. This article discusses implications for
      intervention.

PMID- 15843105
TI  - The functional neuroanatomy of spatial attention in autism spectrum disorder.
AB  - This study investigated the functional neuroanatomical correlates of spatial
      attention impairments in autism spectrum disorders (ASD) using an event-related
      functional magnetic resonance imaging (FMRI) design. Eight ASD participants and 8
      normal comparison (NC) participants were tested with a task that required
      stimulus discrimination following a spatial cue that preceded target presentation
      by 100 msec (short interstimulus interval [ISI]) or 800 msec (long ISI). The ASD
      group showed significant behavioral spatial attention impairment in the short ISI
      condition. The FMRI results showed a reduction in activity within frontal,
      parietal, and occipital regions in ASD relative to the NC group, most notably
      within the inferior parietal lobule. ASD behavioral performance improved in the
      long ISI condition but was still impaired relative to the NC group. ASD FMRI
      activity in the long ISI condition suggested that the rudimentary framework of
      normal attention networks were engaged in ASD including bilateral activation
      within the frontal, parietal, and occipital lobes. Notable activation increases
      were observed in the superior parietal lobule and extrastriate cortex. No
      reliable activation was observed in the posterior cerebellar vermis in ASD
      participants during either long or short ISI conditions. In addition, no frontal
      activation during short ISI and severely reduced frontal activation during long
      ISI was observed in the ASD group. Taken together, these findings suggest a
      dysfunctional cerebello-frontal spatial attention system in ASD. The pattern of
      findings suggests that ASD is associated with a profound deficit in automatic
      spatial attention abilities and abnormal voluntary spatial attention abilities.
      This article also describes a method for reducing the contribution of physical
      eye movements to the blood-oxygenation level dependent activity in studies of
      ASD.

PMID- 15843106
TI  - Community environment and HIV/AIDS-related stigma in China.
AB  - This article examines the contextual effects of community environment on
      individual stigmatizing attitudes toward people with HIV/AIDS in China.
      Multilevel logistic regression models are used to analyze data on 5,658
      respondents aged 15-49 from 66 communities in the Baseline Information,
      Education, and Communication Survey for HIV/AIDS Prevention in China, conducted
      by the State Family Planning Commission in 2000. The results show that a high
      level of HIV/AIDS-related risk behavior in the community and a low level of
      community development are associated with increased HIV/AIDS-related stigma,
      after controlling for respondents' sociodemographic characteristics, including
      extent of knowledge about HIV/AIDS. The findings suggest that interventions for
      reducing HIV/AIDS-related stigma in China should take into account community
      characteristics, such as level of HIV/AIDS-related risk behavior and level of
      development in the community.

PMID- 15843107
TI  - Acceptability of HIV/AIDS counseling and testing among premarital couples in
      China.
AB  - Premarital counseling is required for couples wishing to be married in China. The
      counseling primarily provides information about contraception. We evaluated
      adding premarital HIV/AIDS counseling and voluntary HIV testing to the standard
      counseling. The test was offered free to one group and at the standard cost to
      the other. The proportion of those accepting HIV testing among all participants
      receiving premarital counseling was used as a measure of acceptability. Sixteen
      percent of participants not charged chose to accept testing versus 1.4% of those
      charged ( p < .001). Lack of HIV/AIDS knowledge and charging for the test were
      correlated with refusal. Over 5% of participants admitted to premarital sex, most
      with their fiancee, and a significantly higher portion was female. Only 22% used
      condoms. Study participants were randomized for 1-year follow-up. Only four
      participants reported extramarital sexual activity during that year. Acceptance
      of HIV testing was disappointingly low. Implementing strategies to reduce
      stigmatization and increase knowledge of HIV/AIDS, in addition to not charging
      for testing, may increase the acceptance of HIV testing.

PMID- 15843108
TI  - Unique challenges to preventing perinatal HIV transmission among Hispanic women
      in California: results of a needs assessment.
AB  - To identify rates and factors associated with timely prenatal care (PNC)
      initiation, HIV test counseling, test offering, and test offer acceptance, we
      conducted a semistructured survey of a convenience sample of pregnant/recently
      delivered Hispanic women (n=453, 418 with analyzable data) in four California
      counties in 2000. Only 68.4% and 43.5% of Hispanic women reported receiving an
      HIV test offer and counseling, respectively, though 88.8% of those offered a test
      accepted. After controlling for the effects of age, education, years lived in the
      United States, health insurance coverage, delivery status, and parity, Hispanic
      women who initiated prenatal care in the first trimester were 1.7 times more
      likely to be offered an HIV test and almost 3 times more likely to receive
      counseling than women with a later prenatal care start or no prenatal care.
      Factors associated with timely PNC initiation on multivariate analysis were
      private/HMO insurance (OR=10.7, p < .001), Medi-Cal insurance (OR = 4.32, p <
      .001), being 25-30 years old (OR = 3.0, p = .008), and completion of high school
      (OR = 2.07, p = .01). Key opportunities to prevent perinatal HIV transmission are
      being lost for Hispanic women in California. Interventions to increase timely PNC
      initiation, and to improve test offering by health care providers, may help to
      improve counseling and testing rates for this population.

PMID- 15843109
TI  - Enrollment of minority women and their main sexual partners in an HIV/STI
      prevention trial.
AB  - There is a paucity of empirical reports that quantitatively assess the success of
      recruitment strategies in randomized clinical trials (RCTs) using sampling units
      other than the individual. As innovations in HIV and sexually transmitted
      infection (STI) preventive intervention protocols and targets of change evolve,
      there is a need to examine the efficacy of attendant adaptations to recruitment
      protocols and strategies in the enrollment of study participants. This article
      examines factors related to enrollment of women and their main, male sexual
      partners in an RCT of a relationship-based HIV/STI preventive intervention
      conducted from 1997 to 2001. Among eligible participants (N = 388), findings
      indicate that race/ethnicity, employment status, marital status, and language
      preference were significantly associated with enrollment among eligible,
      potential participants. Additionally, being HIV-positive and having a past or
      current STI were significantly associated with enrollment. These findings
      underscore the need to ensure sufficient representation of all risk groups in
      RCTs, especially those testing innovative HIV/STI preventive intervention
      approaches or using novel enrollment strategies.

PMID- 15843110
TI  - Egocentric HIV risk networks among Puerto Rican crack users in New York and in
      Puerto Rico: impact on sex risk behaviors over time.
AB  - This study examined risk network characteristics of Puerto Rican crack users and
      the relationship between the network and HIV-related sex risk behavior over time.
      The participants (N = 383 in New York; N = 165 in Puerto Rico), recruited through
      street outreach, were interviewed at both baseline and 6-month follow-up. The
      majority of crack users (88%, New York; 92%, Puerto Rico) in the sample named one
      or more personal risk network members. As compared with New York participants,
      crack users in Puerto Rico reported larger risk networks and were more likely to
      engage in sex risk behaviors with strangers or acquaintances. In multivariate
      analyses, a significant variable in predicting sex risk behaviors at follow-up in
      both sites was the baseline measure of the dependent variable. Significant
      network variables were: having any known crack use member less than 6 months and
      having acquaintance/stranger in network in New York; communicating with network
      members about using condoms in Puerto Rico. More attention to sex risk behaviors
      are needed in HIV/AIDS prevention and education programs.

PMID- 15843111
TI  - What's community got to do with it? Implementation models of syringe exchange
      programs.
AB  - Syringe exchange programs (SEPs) have been shown to be highly effective in
      reducing HIV transmission among injection drug users (IDUs). Despite this
      evidence, SEPs have not been implemented in many communities experiencing HIV
      epidemics among IDUs. We interviewed 17 key informants in nine U.S. cities to
      identify factors and conditions that facilitated or deterred the adoption of
      SEPs. Cities were selected to represent diversity in size, geographic location,
      AIDS incidence rates, and SEP implementation. Key informants included HIV
      prevention providers, political leaders, community activists, substance use and
      AIDS researchers, and health department directors. SEPs were established by one
      or more of three types of implementation models: (a) broad community coalition
      support, (b) community activist initiative, and (c) top-down decision making by
      government authorities. In each model, coalition building and community
      consultation were critical steps for the acceptance and sustainability of SEPs.
      When others were not prepared to act, community activists spearheaded SEP
      development, taking risks in the face of opposition, but often lacked the
      resources to sustain their efforts. Leadership from politicians and public health
      officials provided needed authority, clout, and access to resources. Researchers
      and scientific findings lent force and legitimacy to the effort. Rather than
      adopting adversarial positions, successful SEP implementers worked with or
      avoided the opposition. Fear of repercussions and lack of leadership were the
      greatest barriers to implementing SEPs. Communities that successfully implemented
      SEPs were those with activists willing to push the agenda, public officials
      willing to exercise leadership, researchers able to present authoritative
      findings, and proponents who effectively mobilized resources and worked to build
      community coalitions, using persistent but nonadversarial advocacy.

PMID- 15843112
TI  - Condom use and perceived risk of HIV transmission among sexually active HIV
      positive men who have sex with men.
AB  - This study examined the association between HIV transmission risk perception and
      the sexual risk behaviors of HIV-positive men who have sex with men. Respondents
      rated the degree of risk of transmitting HIV through insertive anal intercourse
      and insertive oral sex. We examined (a) the perceived level of HIV transmission
      risk assigned to each sexual behavior and (b) the association between perceived
      risk for HIV transmission and condom use during insertive anal intercourse and
      insertive oral sex. We found for behaviors that have achieved less risk consensus
      that as transmission risk perception increases, so too does the likelihood of
      condom use. This study highlights the need for more research in understanding how
      perceived health risk to others influences protective behaviors.

PMID- 15843113
TI  - Introduction to the special supplement: prevention with persons living with HIV.

PMID- 15843114
TI  - Prevention interventions with persons living with HIV/AIDS: state of the science
      and future directions.
AB  - The National Institutes of Health (NIH/NIMH), the Centers for Disease Control and
      Prevention (CDC), and the HIV/AIDS Bureau of the Health Resources and Services
      Administration (HRSA) support the CDC's Serostatus Approach to Fighting the HIV
      Epidemic (SAFE; Janssen et al., 2001). One aim of the strategy is to help
      individuals living with HIV (and their partners) adopt and sustain HIV and STD
      risk reduction, treatment adherence, and effective strategies for coping with
      HIV/AIDS. Efficacious interventions are needed by community organizations and
      clinics that provide evidence-based services. To expedite translation from
      research to practice, we convened scientist-practitioners, HIV treatment and
      prevention providers, and community/consumer members. In this article, we include
      an overview of prevention trials with HIV-positive persons presented at the
      meeting, discuss strengths and limitations, recommendations for future research,
      and discuss sponsoring agencies' plans for advancing prevention tailored for
      persons living with HIV.

PMID- 15843115
TI  - The Healthy Living Project: an individually tailored, multidimensional
      intervention for HIV-infected persons.
AB  - The NIMH Healthy Living Project (HLP), a randomized behavioral intervention trial
      for people living with HIV, enrolled 943 individuals, including women,
      heterosexual men, injection drug users, and men who have sex with men from Los
      Angeles, Milwaukee, New York, and San Francisco. The intervention, which is based
      on qualitative formative research and Ewart's Social Action Theory, addresses
      three interrelated aspects of living with HIV: stress and coping, transmission
      risk behavior, and medication adherence. Fifteen 90-minute structured sessions,
      divided into 3 modules of five sessions each, are delivered to individuals.
      Sessions are tailored to individuals within a structure that uses role-plays,
      problem solving, and goal setting techniques. A 'Life Project'--or overarching
      goal related to personal striving-provides continuity throughout sessions.
      Because this is an ongoing project with efficacy yet to be established, we do not
      report intervention outcomes. However, the intervention was designed to be useful
      for prevention case management, settings where repeated one-on-one contact is
      possible, and where a structured but highly individualized intervention approach
      is desired.

PMID- 15843116
TI  - Reductions in transmission risk behaviors in HIV-positive clients receiving
      prevention case management services: findings from a community demonstration
      project.
AB  - Prevention case management (PCM) for HIV-infected persons is an HIV risk
      reduction intervention designed to assist clients who are aware of their HIV
      infection and who continue to engage in risk transmission behaviors. PCM combines
      individual risk reduction counseling with case management to address the
      psychosocial factors affecting HIV transmission. More than 350 HIV-positive
      clients participated in PCM in Wisconsin between 2000 and 2003, and 109 completed
      both baseline and follow-up risk assessments. The percentage of clients reporting
      risk transmission behaviors, specifically unprotected vaginal intercourse,
      insertive anal intercourse, or needle sharing with partners of negative or
      unknown HIV status, declined from 41.3% at baseline to 29.4% at follow-up (p =
      0.04). Furthermore, clients showed progression (p < or =.05) through stages of
      change using Prochaska and DiClemente's transtheoretical model on seven domains
      related to HIV transmission risk, including personalizing risk of HIV
      transmission and sexual risk behavior.

PMID- 15843117
TI  - Group-level interventions for persons living with HIV: a catalyst for individual
      change.
AB  - This study describes the perceived influence of group-level HIV interventions on
      persons living with HIV in Los Angeles, California. Funded by the Centers for
      Disease Control and Prevention and developed by a broad range of community
      organizations, group-level interventions ranged from small skills-building
      workshops to large educational forums and to intensive weekend gatherings.
      Recognizing the relationship between psychosocial factors and HIV-related risk
      taking, these interventions were designed not only to provide HIV prevention
      education and develop risk reduction skills but also to bring people together to
      facilitate the formation of supportive relationships. The formative data
      presented here are based on 35 qualitative interviews conducted with a sample of
      intervention participants. Interviews highlight the experiential opportunities
      that group interventions offer with respect to HIV knowledge, social support, HIV
      disclosure skills, and HIV risk reductions. Participants talked highly of their
      experiences in group-level interventions, suggesting that they should be
      considered an important prevention strategy for people living with HIV.

PMID- 15843118
TI  - The other side of the healthy relationships intervention: mental health outcomes
      and correlates of sexual risk behavior change.
AB  - Healthy Relationships is a small-group, social cognitive theory-based HIV
      prevention intervention designed for people living with HIV/AIDS. The Healthy
      Relationships intervention was demonstrated effective in a controlled randomized
      clinical trial. The intervention also integrated stress reduction with sexual
      risk reduction techniques, but the mental health outcomes from the intervention
      have not yet been reported. This study examined the 6-month follow-up mental
      health outcomes of the Healthy Relationships intervention among 81 HIV-positive
      study participants (45 in the Healthy Relationships condition and 36 in the
      health maintenance control condition) who reported sexual relationships with HIV
      negative or unknown HIV status (nonconcordant) partners. Compared with the time
      matched control condition, the Healthy Relationships intervention demonstrated
      significant reductions in perceived HIV-related stress. There was also evidence
      that reductions in perceived HIV-related stress mediated the intervention effects
      on sexual risk behaviors with nonconcordant partners. Results have implications
      for designing the next generation of HIV prevention interventions targeted to
      people living with HIV/AIDS.

PMID- 15843119
TI  - Sexual risk taking among HIV-positive injection drug users: contexts,
      characteristics, and implications for prevention.
AB  - HIV-positive injection drug users (IDUs) ( N = 161) were recruited to complete a
      qualitative interview and a quantitative survey about sexual behavior and
      transmission risk. We identified two contexts in which exposure encounters
      occurred most commonly for HIV-positive IDUs: in intimate serodiscordant
      relationships and in the drug/sex economy. Salient characteristics in both
      contexts included the role of intimacy, drug use and sexual decision making,
      disclosure of HIV status, and perceived responsibility. Although these
      characteristics emerged in both risk contexts, they operated differently within
      each context. The preservation of intimacy was paramount among those in
      serodiscordant relationships, and agreements to take risks were common. In the
      drug/sex economy, serostatus disclosure was uncommon and drug acquisition and use
      played a significant role in sexual risk taking. Our data emphasize a need to
      address the specific transmission risk contexts occurring among HIV-positive IDUs
      and to prioritize social and interpersonal factors when promoting safer sexual
      norms among HIV-positive IDUs.

PMID- 15843120
TI  - Integrating prevention in residential and community care settings: a
      multidimensional program evaluation.
AB  - As people with HIV live longer and healthier lives, ongoing prevention with
      positive individuals has become a new focus of care. Effective prevention with
      positives interventions are emerging and new interventions continue to be
      developed. This article discusses the development and evaluation of the
      prevention for positives intervention developed for a large AIDS service
      organization in Chicago. The intervention consists of case manager based HIV
      prevention education and support within residential and community settings. The
      article describes the intervention and presents the methods and findings of the
      program evaluation. The multidimensional evaluation includes formative and
      process evaluation elements as well as qualitative and quantitative measures (N =
      94). The article concludes with a discussion of the challenges and opportunities
      associated with integrating prevention into care.

PMID- 15843121
TI  - Working with positive men: HIV prevention with black men who have sex with men.
AB  - There is limited empirical evidence on effective HIV/AIDS prevention for Black
      MSM. Few studies have been undertaken to examine the specific ways in which Black
      MSM construct their health and help-seeking practices relative to HIV/AIDS. In
      this article I examine the role of patients and providers as a collaborative unit
      to bring about productive HIV/AIDS outcomes. I report on a qualitative study of
      50 men who participated in semistructured focus groups and individual interviews.
      Major themes are presented and discussed: the personal costs of adherence and
      perceptions about HIV medications and their utility (outcomes), quality of life
      concerns, impact and importance of the relationship with the primary care
      provider, elements of the treatment milieu (proximal variables); and personal
      historical experiences that shape views of health care and health seeking
      (antecedent). A sociocultural model of interaction between patient, provider and
      setting is offered as a framework for working with Black MSM in service delivery
      and further research.

PMID- 15843124
TI  - Health/hygiene, sanitation, and water: is cleanliness next to whatever has
      replaced godliness?

PMID- 15843125
TI  - Promotion of handwashing as a measure of quality of care and prevention of
      hospital-acquired infections in Eritrea: the Keren study.
AB  - A complex interplay of cognitive, socio-economic and technical factors may
      determine hand-washing practice among hospital-based health workers, particularly
      doctors, regardless of the location of the country or hospital they work in.
      OBJECTIVES: To assess quality of care with respect to handwashing practice as a
      routine measure of infection prevention in Keren hospital, a provincial referral
      hospital, second largest in Eritrea; with a view to putting in place quality
      standards and effective means of monitoring and evaluation. DESIGN: Qualitative
      study with a participatory and iterative/dynamic design. METHODS: Semi-structured
      interviews and focus group discussions were held with 34 members of the hospital
      staff; and a total of 30 patients in the medical, surgical and obstetric wards
      were interviewed. Direct observation of handwashing practice and facilities were
      also employed. RESULTS: Although only 30% of health workers routinely washed
      their hands between patient contact, the study revealed genuine interest in
      training and the need to reward good practice in order to motivate health
      workers. Educational intervention and technical training resulted in significant
      improvements in health workers' compliance with hospital infection prevention
      standards. Patient satisfaction with health workers' hygiene practices also
      improved significantly. CONCLUSION: Hospital-based health workers' handwashing
      practice needs to improve globally. There is no room for complacency, however, in
      Eritrea (as indeed in other African countries) where public health services need
      to keep patients' welfare at heart; particularly with respect to women in
      childbirth, as mothers continue to bear the lion's share of post-war rebuilding
      of lives, livelihoods, and the country as a whole.

PMID- 15843126
TI  - The quality of water from protected springs in Katwe and Kisenyi parishes,
      Kampala city, Uganda.
AB  - BACKGROUND: In the sub-urban areas of Kampala city, springs are a major source of
      water for domestic use. Though spring water is considered to be aesthetically
      acceptable for domestic use, presence of poorly designed pit latrines, poor solid
      waste management as well as poor and inadequate spring protection, may lead to
      contamination of spring water with pathogenic bacteria. OBJECTIVES: The
      objectives of the study were to examine the bacteriological quality of water from
      ten springs in Katwe and Kisenyi parishes of Kampala, and to identify and
      quantify risks for spring water contamination with faecal bacteria. METHODS: A
      cross-sectional sanitary risk assessment using a standardised format was carried
      out in ten randomly selected springs in the parishes of Katwe and Kisenyi
      parishes in Kampala. A total of 80 samples of water from these springs were
      collected from December 2001 to March 2002. The samples were analysed for
      indicators of faecal contamination: total coliforms, faecal coliforms and faecal
      streptococci. Physico-chemical parameters were measured. RESULTS: Aggregate
      qualitative sanitary risk scores ranged from medium to high. The total coliform
      counts in 90% of the samples exceeded the WHO guideline for drinking water. All
      the samples had faecal coliform counts above the WHO guideline. A strong
      correlation (r2= 887) was observed between the median faecal coliform counts and
      the sanitary risk score. Sixty percent of the samples had nitrate levels above
      the WHO recommended limit. There was no correlation between the levels of
      chlorides and nitrates and levels of indicators of faecal bacterial
      contamination. CONCLUSIONS: The sanitary risk assessment score is a reliable tool
      for predicting the likely levels of bacterial contamination of spring water.
      Water from the ten protected springs studied is unsuitable for drinking without
      treatment.

PMID- 15843127
TI  - Factors that could motivate people to adopt safe hygienic practices in the
      Eastern Cape Province, South Africa.
AB  - BACKGROUND: Approximately 18 million South Africans do not have access to
      adequate sanitation. This problem is not unique to South Africa but is a
      challenge to many developing countries. OBJECTIVES: The purpose of this
      qualitative study was to gain insight and understanding of factors that could
      motivate people to adopt safe hygienic practices. METHODS: A non-probability
      purposive sample of 122 participants was drawn from sanitation stakeholder
      organisations in the Eastern Cape Province. Of these, 74 were male and 48 were
      female. The mean age of the participants was 40.1 years. The 122 participants
      were divided into 15 focus groups, each consisting of about eight members. The
      focus group discussions were conducted using seven guiding questions. Responses
      were examined and clustered in terms of the primary focus group questions.
      RESULTS: Regular water supply, provision of sanitation facilities, stakeholder
      participation and improvement of consumer sanitation knowledge are factors which
      can motivate people to adopt safe hygienic practices. CONCLUSIONS: There are
      cultural, educational, economic, institutional, environmental and psycho-social
      factors that could motivate people to adopt safe hygienic practices.

PMID- 15843128
TI  - Reversal of left ventricular hypertrophy by propranolol in hypertensive rats.
AB  - BACKGROUND: Hypertension contributes significantly to the development of left
      ventricular hypertrophy. Left ventricular hypertrophy is associated with
      increased incidence of sudden cardiac death. Recognition and management of
      hypertension is, therefore, imperative. OBJECTIVE: To establish whether
      propranolol can reverse left ventricular hypertrophy in hypertensive rats.
      METHODS: Hypertension was induced in male albino rats by giving them 1% NaCl
      solution as their only drink for four weeks. Propranolol was then administered
      orally to one of the four groups of rats used in this study. Systolic blood
      pressure of each rat was measured twice a week using a modified tail-cuff method.
      Each rat was then sacrificed, its heart excised from the chest cavity and
      geometric studies carried on the left ventricle. RESULTS: Excessive intake of
      sodium salt by the rats caused an increase in their systolic blood pressure which
      was accompanied by left ventricular hypertrophy. The elevated blood pressure
      (139.4 +/- 0.5 mm Hg) was, however, brought back to normal (108.4 +/- 0.2 mm Hg)
      by propranolol. Data on weight, thickness, and volume of the left ventricle
      strongly indicated that propranolol can reverse ventricular hypertrophy.
      CONCLUSION: Propranolol reverses left ventricular hypertrophy besides lowering
      elevated systolic blood pressure in rats.

PMID- 15843129
TI  - Use of sulfonamides in layers in Kampala district, Uganda and sulfonamide
      residues in commercial eggs.
AB  - BACKGROUND: Use of antimicrobials like sulfonamides in production of layers is a
      public health risk since it inevitably results in sulfonamide residues in eggs.
      The presence of the residues may be influenced by knowledge, attitudes and
      practices of farmers regarding use of sulfonamides (and other antimicrobials) in
      poultry. OBJECTIVE: The study aimed at assessing the possible contribution of the
      knowledge, attitudes and practices of poultry farmers to the presence/levels of
      sulfonamide residues in hen eggs. METHODS: A descriptive cross sectional study
      was done in the 5 political divisions (and surroundings) of Kampala district.
      Sixty farmers were systematically sampled from a list of poultry farmers in
      Kampala and a semi-structured questionnaire administered. Each farmer provided
      sixty eggs for analysis of sulfadiazine and sulfamethazine residues. Whole eggs
      were homogenized in acetonitrile and centrifuged twice, extracts evaporated and
      residues dissolved in mobile phase (32:68, methanol: potassium di-hydrogen
      phosphate). Fats were removed using hexane while anhydrous sodium chloride was
      added to break emulsions. Extracts were analyzed by reverse phase high
      performance liquid chromatography with photodiode array detector. RESULTS: Ninety
      five percent of the farmers never observed withdrawal periods although 80% of
      them knew the importance of withdrawal periods. However, farmers noted that they
      play a great role in ensuring a safe food supply. Most farmers attributed the non
      observance of withdrawal periods to poverty and fear to lose their investments.
      Ninety-eight percent of the samples had detectable levels of the sulfonamides.
      Meanwhile, 98.3% of the samples that had detectable sulfonamide residues came
      from farmers who applied antimicrobials in feeds/ water. CONCLUSION: Consumers of
      hen eggs in Kampala district are at high risk of sulfonamide residue exposure due
      to poor farming/ regulatory practices.

PMID- 15843130
TI  - Traditional herbal remedies used in the management of sexual impotence and
      erectile dysfunction in western Uganda.
AB  - BACKGROUND: The utilisation of ethnobotanical indigenous knowledge is vital in
      male sexual reproductive health care delivery in western Uganda. Reproductive
      health care is the second most prevalent health care problem in Africa. However,
      this concept of reproductive health care has been focusing mainly on women
      disregarding men. Thus, some diseases such as sexual impotence and erectile
      dysfunction that deserve mention are regarded as petty though important in
      economic productivity, family stability and sexually transmitted diseases control
      including HIV/AIDS. OBJECTIVE: This study was carried out mainly to document
      medicinal plants used in the treatment of sexual impotence and erectile
      dysfunction disorders in western Uganda. METHODS: The medical ethnobotanical
      indigenous knowledge were collected by visiting traditional healers and
      documenting the medicinal plants used and other socio-cultural aspects allied
      with sexual impotence and erectile dysfunction. The methods used to collect the
      relevant information regarding the medicinal plants used included informal and
      formal discussions, field visits and focused semi-structured interviews. RESULTS:
      Thirty-three medicinal plants used in the management of sexual impotence and
      erectile dysfunction were documented and Citropsis articulata and Cola acuminata
      were among the highly utilized medicinal plants. CONCLUSION: From the
      researchers' point of view, the usage of herbal remedies in managing male sexual
      disorders is useful because of long cultural history of utilisation and the
      current renewed interest in natural products to sustain health globally. As a way
      recognising the values and roles of traditional medical knowledge in health care
      provision, further research into the efficacy and safety of herbal remedies in
      male sexual disorders is precious in Uganda and beyond. More so, the
      establishment of rapport between relevant government department in Ministry of
      Health, modern health workers through collaborative and networking ventures with
      traditional healers under close supervision and monitoring of herbal treatments
      is noble.

PMID- 15843131
TI  - Clinical presentation and management of alleged sexually assaulted females at
      Mulago hospital, Kampala, Uganda.
AB  - OBJECTIVE: To determine the presentation and treatment offered to sexually
      assaulted females attending emergency gynaecological ward in Mulago Hospital,
      Kampala, Uganda. SETTING: Mulago hospital gynaecological emergency ward. STUDY
      DESIGN: Prospective descriptive study. PARTICIPANTS: Fifty eight sexually
      assaulted females were recruited from 1 st March 2000 to 31 st December 2000.
      They were interviewed, examined, given appropriate treatment and followed up for
      three months. OUTCOME VARIABLES: Socio demographic characteristics, genital and
      bodily injuries, relationship to the assailant, and prevalence of sexually
      transmitted infections. RESULTS: The mean age was 9.5 with a range of 1-35 years.
      Seventy two percent of the victims were children below 12 years. Fifty percent of
      the assault occurred at the assailant's home. The majority (79.3%) of the victims
      knew the assailant and cases of gang rape were only 6.9%. The injuries sustained
      were extra genital (19.0%), genital (75.4%). The emotional or psychological
      disturbance was present in 22.4% of the patients. The sexually transmitted
      infections found included trichomonas vaginalis (1.7%) and syphilis (3.7%). All
      cases received counseling and prophylactic treatment for sexually transmitted
      infections. Those in reproductive age group were offered emergency contraception.
      None of the victims got post exposure HIV therapy because it was not available in
      the hospital. CONCLUSION: Sexual assault is common in Uganda and is one of the
      most dehumanizing human crimes against women. It is associated with adverse
      medical and social problems. There is urgent need to sensitize the community
      about reporting early for medical treatment after sexual assault.

PMID- 15843132
TI  - Human immunodeficiency virus (HIV) seropositivity and hepatitis B surface
      antigenemia (HBSAG) among blood donors in Benin city, Edo state, Nigeria.
AB  - BACKGROUND: Human Immunodeficiency Virus and Hepatitis B virus are blood borne
      pathogens that can be transmitted through blood transfusion and could pose a huge
      problem in areas where mechanisms of ensuring blood safety are suspect. This
      study became necessary in a population where most of the blood for transfusion is
      from commercial blood donors. METHOD: A total of 130 donors comprising 120
      commercial donors and 10 voluntary donors were tested for antibodies to human
      immunodeficiency virus and hepatitis B surface antigen in Benin city using
      Immunocomb HIV - 1 and 2 Biospot kit and Quimica Clinica Aplicada direct latex
      agglutination method respectively. RESULTS: Thirteen (10%) samples were HIV
      seropositive and 7(5.8%) were HBsAg positive. The age bracket 18 - 25years had
      the highest numbers of donors and also had the highest number of HBsAg positive
      cases (7.8%) while the age group 29 - 38years had highest number of HIV
      seropositive cases. CONCLUSION: High prevalence of HIV antibodies and Hepatitis B
      surface antigen was found among commercial blood donors. Appropriate and
      compulsory screening of blood donors using sensitive methods, must be ensured to
      prevent post transfusion hepatitis and HIV.

PMID- 15843133
TI  - Evaluation criteria for the district health management information systems:
      lessons from the Ministry of Health, Kenya.
AB  - BACKGROUND: The District Health Management Information Systems (DHMISs) were
      established by the Ministry of Health (MoH) in Kenya more than two decades ago.
      Since then, no comprehensive evaluation has been undertaken. This can partly be
      attributed to lack of defined criteria for evaluating them. OBJECTIVE: To propose
      evaluation criteria for assessing the design, implementation and impact of DHMIS
      in the management of the District Health System (DHS) in Kenya. METHODS: A
      descriptive cross-sectional study conducted in three DHSs in Kenya: Bungoma,
      Murang'a and Uasin Gishu districts. Data was collected through focus group
      discussions, key informant interviews, and documents' review. The respondents,
      purposely selected from the Ministry of Health headquarters and the three DHS
      districts, included designers, managers and end-users of the systems. RESULTS: A
      set of evaluation criteria for DHMISs was identified for each of the three phases
      of implementation: pre-implementation evaluation criteria (categorised as policy
      and objectives, technical feasibility, financial viability, political viability
      and administrative operability) to be applied at the design stage; concurrent
      implementation evaluation criteria to be applied during implementation of the new
      system; and post-implementation evaluation criteria (classified as internal -
      quality of information; external - resources and managerial support; ultimate -
      systems impact) to be applied after implementation of the system for at least
      three years. CONCLUSIONS: In designing a DHMIS model there is need to have built
      in these three sets of evaluation criteria which should be used in a phased
      manner. Pre-implementation evaluation criteria should be used to evaluate the
      system's viability before more resources are committed to it; concurrent
      (operational) - implementation evaluation criteria should be used to monitor the
      process; and post-implementation evaluation criteria should be applied to assess
      the system's effectiveness.

PMID- 15843134
TI  - Pattern of dental caries in Mulago Dental School clinic, Uganda.
AB  - Information on dental caries among patients attending Mulago Hospital is scarce.
      Yet knowledge of the pattern of caries can be used to plan preventive and
      treatment interventions. This study describes the pattern of dental caries (in
      terms of age group, tooth and tooth surface and gender) among patients attending
      the Public Health Dental Officers School Clinic, Mulago Hospital. METHODOLOGY: A
      review of patients' treatment records for the period 1995 to 1999 was done. A
      total of 1800 cards were reviewed for the diagnosis of dental caries, age, gender
      and the data was analyzed using EPI INFO 6 program. The patients were from both
      urban and peri-urban settings and were aged between 10-90 years. RESULTS: The
      results showed that the most frequently affected tooth surface was the occlusal
      (68.8%) followed by the interproximal (24%) and the least affected was the
      lingual/palatal (1.5%). The second molars were found to be the most affected of
      all teeth, with tooth 37(12%), 47(11%), 17(9.5%) and 27 (9.1%). The distribution
      of caries was higher in the lower than the upper jaw. There was a slight
      difference in sex predilection with females having 54.5% and males 45.5% of the
      lesions and the age group most affected was 20-29 years. CONCLUSION: The results
      showed a high occurrence of occlusal surface caries in molars especially the
      second molars in the 20-29 age group in the patients attending the Public Health
      Dental Officers School Clinic, Mulago Hospital.

PMID- 15843135
TI  - Acute brucella meningomyeloencephalo-spondylosis in a teenage male.
AB  - BACKGROUND: Brucellosis has been known from the time of Hippocrates. In 1885 Sir
      David Bruce isolated the causative organism from the spleens of soldiers who had
      died from "Malta disease" (now brucellosis). There are 4 species of brucella
      pathogenic to humans and each of them has a specific types of animal reservoir:
      B.arbotus (cattle, buffalo), B.melitensis (goats, sheep, camels), B.suis (pigs),
      B.canis (Dogs). Humans are infected when they are exposed to body fluids from an
      infected animal. The symptoms and signs of brucellosis are protean. Diagnosis is
      usually dependent on clinical features and serology or culture. OBJECTIVES: To
      describe a case of neurobrucellosis, raise awareness about the existence of the
      disease in Uganda and Africa in general and share our experiences in its
      diagnosis and management. METHODS: A male teenager was admitted with symptoms and
      signs of an acute meningo-encephalitis. He underwent clinical, laboratory and
      basic radiological evaluation. RESULTS: The un-incubated brucella titer was
      significantly reactive(1:160).Oblique-view cervical x-rays showed early
      osteophyte formation with encroachment on the vertebral foramina on the left hand
      side. A diagnosis of acute brucella meningomyeloencephalo-spondylosis was made
      and the patient was successfully treated using conventional therapy for
      brucellosis (oral doxycycline for 6weeks and IM streptomycin for 2 weeks).
      CONCLUSIONS: Neurobrucellosis though said to be rare, is a reality in our health
      units should be considered in the differential diagnosis of neurological and
      psychiatric illnesses. The good news is that it is curable and is responsive to
      drugs used for other forms of brucellosis.

PMID- 15843136
TI  - Cost effective management of duodenal ulcers in Uganda: interventions based on a
      series of seven cases.
AB  - BACKGROUND: Our understanding of the cause and treatment of peptic ulcer disease
      has changed dramatically over the last couple of decades. It was quite common
      some years ago to treat chronic ulcers surgically. These days, the operative
      treatment is restricted to the small proportion of ulcer patients who have
      complications such as perforation. The author reports seven cases of perforated
      duodenal ulcers seen in a surgical clinic between 1995 and 2001. Recommendations
      on the criteria for selecting the appropriate surgical intervention for patients
      with perforated duodenal ulcer are given. OBJECTIVE: To decide on the appropriate
      surgical interventions for patients with perforated duodenal ulcer. DESIGN: These
      are case series of 7 patients who presented with perforated duodenal ulcers
      without a history of peptic ulcer disease. MATERIALS AND METHODS: Seven patients
      presented with perforated duodenal ulcer 72 hours after perforation in a
      specialist surgical clinic in Kampala were analyzed. Appropriate management based
      on these patients is suggested. RESULTS: These patients were initially treated in
      upcountry clinics for acute gastritis from either alcohol consumption or
      suspected food poisoning. There was no duodenal ulcer history. As a result, they
      came to specialist surgical clinic more than 72 hours after perforation.
      Diagnosis of perforated duodenal ulcer was made and they were operated using the
      appropriate surgical intervention. CONCLUSION: Diagnosis of hangovers and acute
      gastritis from alcoholic consumption or suspected food poisoning should be
      treated with suspicion because the symptoms and signs may mimic perforated peptic
      ulcer in "silent" chronic ulcers. The final decision on the appropriate surgical
      intervention for patients with perforated duodenal ulcer stratifies them into two
      groups: The previously fit patients who have relatively mild physiological
      compromise imposed on previously healthy organ system by the perforation can
      withstand the operative stress of definitive procedure. The Second category
      includes patients who are critically ill, who poorly tolerate any operation and
      hence poor surgical risks. These require urgent, adequate resuscitation and
      simple suture with omental patch.

PMID- 15843138
TI  - Bridging the health gap in Uganda: the surgical role of the clinical officer.
AB  - INTRODUCTION: A scarcity of trained medical personnel impedes Uganda's ability to
      deliver healthcare effectively. The role of the Clinical Officer (CO) was
      established to assist the provision of primary healthcare to rural communities.
      METHODS: Twenty COs, attending a clinical course, responded to a structured
      questionnaire to determine their local investigative resources, the cases
      encountered by them in the two-week period preceding the course and the surgical
      and obstetric procedures that they felt able to perform. RESULTS: The majority of
      respondents did not have access to biochemical or radiological investigations.
      Fifty-five percent had access to basic haematology and urine microscopy. The
      majority of the case-mix encountered by the COs was medical (median 60 %) but
      they also encountered a proportion of surgical (median 12.5 %) and obstetric
      cases (median 15 %). COs felt confident in performing routine obstetric
      procedures as well as offering basic wound and surgical infection management.
      CONCLUSION: COs already provide a vital role in the delivery of healthcare in
      Uganda. Their surgical role could be augmented through further education and
      training. This might help to bridge the gap between overwhelming demand for
      medical services and a scant supply of trained personnel.

PMID- 15843137
TI  - Pharmacological therapy of female urinary incontinence.
AB  - BACKGROUND: Although not a life threatening condition, UI is a common problem in
      women that produces embarrassing and debilitating symptoms, severely affects the
      quality of life and represents a significant public health problem. The bladder
      and urethra in women constitute a functional unit that is controlled by a complex
      interplay between the central and peripheral cholinergic and noradrenergic
      nervous systems and local regulatory factors. A substantial part of urethral tone
      in women is also mediated through the effect of estrogen on urethral mucosal
      function. Theoretically, detrusor instability can be improved by agents that
      decrease detrusor contractility and genuine stress incontinence by agents that
      increase outlet resistance. OBJECTIVE: To review the use of various drugs in
      treatment of female urinary incontinence [UI] and present the current evidence
      based recommendations. METHODS: Systematic review of literature. RESULTS: The
      strength of evidence for the use of such agents, however, varies from data
      obtained from pharmacological and physiological experiments to those derived from
      clinical studies. Hence, the use of some of the currently prescribed drugs for
      treatment of female UI is founded more on tradition than on evidence based on
      results from controlled clinical trials. There is also an urgent medical need for
      a new smooth muscle agent for treating UI in women because current drug therapy
      of UI is either inadequate or ineffective. Therefore, further clinical experience
      with drugs that selectively modulate the electrophysiological properties and the
      intracellular pathways of the smooth muscles of the lower urinary tract in women
      as therapeutic agents for UI is awaited with interest.

PMID- 15843141
TI  - The structure of the juvenile hormone binding protein gene from Galleria
      mellonella.
AB  - Juvenile hormone (JH) and ecdysone are the key hormones controlling insect growth
      and development. The juvenile hormone binding protein (JHBP) is the first member
      in the array of proteins participating in JH signal transmission. In the present
      report a whole jhbp gene sequence (9790 bp) is described. The jhbp gene contains
      four introns (A-D). All the introns have common flanking sequences: GT at the 5'
      and AG at the 3' end. The first intron is in phase 1, the second in phase 2, and
      the third and fourth in phase 1. An analysis of these sequences suggests that U2
      class spliceosomes are involved in intron excision from pre-mRNA. Several
      horizontally transmitted elements from other genes were found in the introns. All
      jhbp exons are positioned in local AT-reach regions of the gene. A search for
      core promoter regulatory elements revealed that the TATA box starts 29 bp
      preceding the start of transcription; the sequence TCAGTA representing a putative
      initiator sequence (Inr) starts at position +14. Eight characteristic sequences
      for binding Broad-Complex gene products, which coordinate the ecdysone temporal
      response, are present in the non-coding sequence of the jhbp gene. An analysis of
      exon locations and intron phases indicates that jhbp gene organization is related
      to the retinol binding protein gene, a member of the lipocalin family.

PMID- 15843142
TI  - Interaction of thiamin diphosphate with phosphorylated and dephosphorylated
      mammalian pyruvate dehydrogenase complex.
AB  - Kinetic and binding studies were carried out on substrate and cofactor
      interaction with the pyruvate dehydrogenase complex from bovine heart.
      Fluoropyruvate and pyruvamide, previously described as irreversible and
      allosteric inhibitors, respectively, are strong competitive inhibitors with
      respect to pyruvate. Binding of thiamin diphosphate was used to study differences
      between the active dephosphorylated and inactive phosphorylated enzyme states by
      spectroscopic methods. The change in both the intrinsic tryptophan fluorescence
      and the fluorescence of the 6-bromoacetyl-2-dimethylaminonaphthalene-labelled
      enzyme complex produced on addition of the cofactor showed similar binding
      behaviour for both enzyme forms, with slightly higher affinity for the
      phosphorylated form. Changes in the CD spectrum, especially the negative Cotton
      effect at 330 nm as a function of cofactor concentration, both in the absence and
      presence of pyruvate, also revealed no drastic differences between the two enzyme
      forms. Thus, inactivation of the enzyme activity of the pyruvate dehydrogenase
      complex is not caused by impeding the binding of substrate or cofactor.

PMID- 15843143
TI  - Purification and characterization of a chitinase-like antifungal protein from
      black turtle bean with stimulatory effect on nitric oxide production by
      macrophages.
AB  - An antifungal protein was isolated from black turtle bean, Phaseolus vulgaris cv.
      "Black Turtle". The purified protein displayed an N-terminal amino acid sequence
      with 60-80% homology to chitinases. The isolated protein specifically inhibited
      two species of fungi, namely Fusarium oxysporum and Mycosphaerella arachidicola ,
      among several phytopathogenic fungi tested. Its antifungal activity was retained
      after incubation at 60 degrees C for 15 minutes, diminished after exposure to 80
      degrees C, and was completely abrogated after treatment at 100 degrees C. The
      antifungal protein had higher thermostability than the antifungal protein
      mollisin from chestnut. It stimulated nitric oxide production by murine
      peritoneal macrophages, but exerted neither mitogenic nor cytotoxic activity on
      murine splenocytes, activities that may be related to allergic responses.

PMID- 15843144
TI  - Nitric oxide covalently labels a 6-hydroxydopa-derived free radical intermediate
      in the catalytic cycle of copper/quinone-containing amine oxidase from lentil
      seedlings.
AB  - The reaction of NO-derivatized polyamines called "NONOates" with an amine oxidase
      from lentil seedlings was studied. 3,3-Bis(aminoethyl)-1-hydroxy-2-oxo-1-triazene
      (DETA-NONOate) and 3,3'-(hydroxynitrosohydrazino)bis-1-propanamine (DPTA-NONOate)
      were found to be irreversible inactivators of the lentil enzyme. The spectrum of
      the protein was strongly affected in the course of reaction with both compounds,
      leading to the formation of a covalent adduct with a stable band at 334 nm. The
      corresponding amine compounds diethylentriamine (DETA) and norspermidine (DPTA)
      were substrates of the lentil enzyme that did not lead to enzyme inactivation.
      Diethylamine-NONOate, not containing amino groups, was found to be an
      irreversible inactivator of the amine oxidase only in the presence of a
      substrate. Since all NONOates spontaneously decompose in solution with release of
      NO, it seems as if the latter is responsible for the enzyme inhibition. The
      insensitivity of the native enzyme to NO suggested that this compound was
      unreactive toward both the cofactors, 6-hydroxydopa quinone (TPQ) and Cu(II), and
      thus a model for the irreversible inactivation could involve the attack by NO of
      the Cu(I)-semiquinolamine radical catalytic intermediate.

PMID- 15843145
TI  - Plasmodium falciparum glutaredoxin-like proteins.
AB  - Glutaredoxin-like proteins form a new subgroup of glutaredoxins with a serine
      replacing the second cysteine in the CxxC-motif of the active site. Yeast Grx5 is
      the only glutaredoxin-like protein studied biochemically so far. We identified
      and cloned three genes encoding glutaredoxin-like proteins from the malaria
      parasite Plasmodium falciparum (Pf Glp1, Pf Glp2, and Pf Glp3) containing a
      conserved cysteine in the CGFS-, CKFS-, and CKYS-motif, respectively. Here, we
      describe biochemical properties of Pf Glp1 and Pf Glp2. Cys 99, the only cysteine
      residue in Pf Glp1, has a pK(a) value as low as 5.5 and is able to mediate
      covalent homodimerization. Monomeric and dimeric Pf Glp1 react with GSSG and GSH,
      respectively. Pf Glp2 is monomeric and both of its cysteine residues can be
      glutathionylated. Molecular models reveal a thioredoxin fold for the putative C
      terminal domain of Pf Glp1, Pf Glp2, and Pf Glp3, as well as conserved residues
      presumably required for glutathione binding. However, Pf Glp1 and Pf Glp2 neither
      possess activity in a classical glutaredoxin assay nor display activity as
      glutathione peroxidase or glutathione S-transferase. Mutation of Ser 102 in the
      CGFS-motif of Pf Glp1 to cysteine did not generate glutaredoxin activity either.
      We conclude that, despite their ability to react with glutathione, glutaredoxin
      like proteins are a mechanistically and functionally heterogeneous group with
      only little similarities to canonical glutaredoxins.

PMID- 15843146
TI  - Characterization of the glyoxalases of the malarial parasite Plasmodium
      falciparum and comparison with their human counterparts.
AB  - The glyoxalase system consisting of glyoxalase I (GloI) and glyoxalase II (GloII)
      constitutes a glutathione-dependent intracellular pathway converting toxic 2
      oxoaldehydes, such as methylglyoxal, to the corresponding 2-hydroxyacids. Here we
      describe a complete glyoxalase system in the malarial parasite Plasmodium
      falciparum. The biochemical, kinetic and structural properties of cytosolic GloI
      (cGloI) and two GloIIs (cytosolic GloII named cGloII, and tGloII preceded by a
      targeting sequence) were directly compared with the respective isofunctional host
      enzymes. cGloI and cGloII exhibit lower K(m) values and higher catalytic
      efficiencies (k(cat)/K(m) ) than the human counterparts, pointing to the
      importance of the system in malarial parasites. A Tyr185Phe mutant of cGloII
      shows a 2.5-fold increase in K(m) , proving the contribution of Tyr185 to
      substrate binding. Molecular models suggest very similar active sites/metal
      binding sites of parasite and host cell enzymes. However, a fourth protein, which
      has highest similarities to GloI, was found to be unique for malarial parasites;
      it is likely to act in the apicoplast, and has as yet undefined substrate
      specificity. Various S-(N-hydroxy-N-arylcarbamoyl)glutathiones tested as P.
      falciparum Glo inhibitors were active in the lower nanomolar range. The Glo
      system of Plasmodium will be further evaluated as a target for the development of
      antimalarial drugs.

PMID- 15843147
TI  - Transcriptional down-regulation of neurotrophin-3 in chronic obstructive
      pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) leads to progressive development of
      airflow limitation and is characterised by cough, mucus hypersecretion and
      inflammatory changes. These characteristic features of the disease may be
      modulated by neural mediators such as neurotrophins (NT). Here we examined the
      expression and transcriptional regulation of neurotrophins in bronchial biopsies
      of COPD patients and compared the data to control biopsies. Histology revealed
      characteristic changes in the COPD tissues, including remodelling of the
      epithelial lining. RT-PCR demonstrated the mRNA expression of neurotrophins in
      all biopsies. Immunohistochemistry confirmed the expression of different
      proteins. To assess changes in the transcriptional expression level, quantitative
      real-time PCR was carried out and revealed differential mRNA expression of
      neurotrophins, with marked down-regulation of NT-3 mRNA expression and constant
      levels of nerve growth factor (NGF), brain-derived nerve factor (BDNF), and NT
      4/5 mRNA expression. The present data on neurotrophin-specific transcriptional
      down-regulation of NT-3 in human COPD indicate a pathophysiological role for
      neurotrophins in COPD.

PMID- 15843148
TI  - Limb girdle muscular dystrophy in a sibling pair with a homozygous Ser606Leu
      mutation in the alternatively spliced IS2 region of calpain 3.
AB  - Previous family studies revealed a large number of calpain 3 ( CAPN3 ) mutations
      that cause recessive forms of limb girdle muscular dystrophy (LGMD2A) with
      selective atrophy of the proximal limb muscles. Correlations between the nature
      and site of a particular mutation and its corresponding phenotype, however, can
      only be established from homozygous mutations, which are particularly rare in the
      alternatively spliced NS, IS1 and IS2 regions of CAPN3. Here we identified a
      sibling pair with LGMD2A-type muscular dystrophy caused by a homozygous Ser606Leu
      (S606L) substitution in the IS2 linker domain. Normal protein levels, unaltered
      myofibrillar targeting and conserved calcium-induced autocatalytic activity of
      the mutated protein could be demonstrated in muscle biopsies from one patient.
      Despite this inconspicuous modification of the IS2 linker between domains III and
      IV, both patients developed signs and symptoms of the disease within their second
      decade of life. The unexpected severity of the clinical manifestation points to
      the high relevance of the calpain 3-specific IS2 segment between domains III and
      IV. We conclude that the structural motif around the Ser606 residue represents an
      important functional site that may regulate the transient activation and limited
      proteolysis of calpain 3.

PMID- 15843149
TI  - GRIP1 mediates the interaction between the amino- and carboxyl-termini of the
      androgen receptor.
AB  - The androgen receptor (AR) mediates transactivation of target genes by acting as
      a dimer in which its amino-terminal domain (AR-NTD) interacts with its carboxyl
      terminal, ligand-binding domain (AR-LBD) (N/C interaction). Here we assessed if
      and how AR N/C interaction relates to AR transactivation activity and how the
      p160 coactivator GRIP1 participates in both processes. The concentration of
      dihydrotestosterone needed for half-maximal N/C interaction was approximately 10
      fold higher than for half-maximal transactivation, indicating a disparity between
      the two processes. Although a mutation of an LXXLL-like motif, 23 FQNLF 27 --> 23
      FQNAA 27 , in the AR-NTD abolished AR N/C interaction, it could be restored by
      the co-expression of the coactivator GRIP1. Co-expression of mutated forms of
      GRIP1, possessing alterations known to abolish either of the two AR interaction
      domains, could not restore AR N/C interaction, suggesting that wild-type GRIP1
      normally bridges the two AR domains. Although AR transactivation activity can
      proceed without AR N/C interaction, we propose that part of the GRIP1
      coactivation activity resides in its ability to bind both AR-NTD and -LBD, to
      stabilize the N/C complex and allow for secondary cofactors to be recruited more
      efficiently. Our results also indicate that AR N/C interaction enhances but is
      not necessary for AR transactivation activity.

PMID- 15843150
TI  - Dual concentration-dependent activity of thyroglobulin type-1 domain of testican:
      specific inhibitor and substrate of cathepsin L.
AB  - The thyroglobulin type-1 (Tg-1) domain is a protein module that occurs in a
      variety of secreted and membrane proteins and is recognised as a potent inhibitor
      of cysteine peptidases. We present here some properties of the Tg-1 domain of
      human testican, a modularly organised proteoglycan secreted mainly by brain
      cells, the exact in vivo function of which is not yet clear. The domain was
      prepared as a recombinant protein in a Pichia pastoris expression system and its
      activity was demonstrated by specific and selective inhibition of cathepsin L
      (K(i) =0.14 nM). Interaction at high enzyme and inhibitor concentrations resulted
      in degradation of the domain by cathepsin L, which was not observed under
      conditions used for the determination of kinetic parameters. No inhibitory
      activity could be detected for cathepsin K, but it exhibited a very similar
      degradation pattern. Homology modelling provided a good explanation for the
      different behaviour observed with the two enzymes. Firstly, the steric fit
      between the interfaces of testican domain and cathepsin L is stabilised by
      numerous favourable forces, while no such interactions are evident in the complex
      with cathepsin K, and repulsive interactions even prevent access of the domain to
      the active site of papain. Secondly, the prolonged first loop of the domain
      occupies a position near the catalytic cysteine residue in a more substrate-like
      manner, enabling cleavage of the Gly22-Ala23 bond.

PMID- 15843151
TI  - Proteolysis of insulin-like growth factor binding proteins (IGFBPs) by calpain.
AB  - Calpains are non-lysosomal, Ca 2+ -dependent cysteine proteases, which are
      ubiquitously distributed across cell types and vertebrate species. The rules that
      govern calpain specificity have not yet been determined. To elucidate the
      cleavage pattern of calpains, we carried out calpain-induced proteolytic studies
      on the insulin-like growth factor binding proteins IGFBP-4 and -5. Proteolysis of
      IGFBPs is well characterized in numerous reports. Our results show that calpain
      cleavage sites are in the non-conserved unstructured regions of the IGFBPs.
      Compilation of the calpain-induced proteolytic cleavage sites in several proteins
      reported in the literature, together with our present study, has not revealed
      clear preferences for amino acid sequences. We therefore conclude that calpains
      seem not to recognize amino acid sequences, but instead cleave with low sequence
      specificity at unstructured or solvent-exposed fragments that connect folded,
      stable domains of target proteins.

PMID- 15843152
TI  - Single zinc-finger extension: enhancing transcriptional activity and specificity
      of three-zinc-finger proteins.
AB  - In order to demonstrate that an existing zinc-finger protein can be simply
      modified to enhance DNA binding and sequence discrimination in both episomal and
      chromatin contexts using existing zinc-finger DNA recognition code data, and
      without recourse to phage display and selection strategies, we have examined the
      consequences of a single zinc-finger extension to a synthetic three-zinc-finger
      VP16 fusion protein, on transcriptional activation from model target promoters
      harbouring the zinc-finger binding sequences. We report a nearly 10-fold enhanced
      transcriptional activation by the four-zinc-finger VP16 fusion protein relative
      to the progenitor three-finger VP16 protein in transient assays and a greater
      than five-fold enhancement in stable reporter-gene expression assays. A marked
      decrease in transcriptional activation was evident for the four-zinc-finger
      derivative from mutated regulatory regions compared to the progenitor protein, as
      a result of recognition site-size extension. This discriminatory effect was shown
      to be protein concentration-dependent. These observations suggest that four-zinc
      finger proteins are stable functional motifs that can be a significant
      improvement over the progenitor three-zinc-finger protein, both in terms of
      specificity and the ability to target transcriptional function to promoters, and
      that single zinc-finger extension can therefore have a significant impact on DNA
      zinc-finger protein interactions. This is a simple route for modifying or
      enhancing the binding properties of existing synthetic zinc-finger-based
      transcription factors and may be particularly suited for the modification of
      endogenous zinc-finger transcription factors for promoter biasing applications.

PMID- 15843153
TI  - Expression of the plasma prekallikrein gene: utilization of multiple
      transcription start sites and alternative promoter regions.
AB  - The plasma prekallikrein gene is expressed in many different human tissues at
      distinctly different levels and therefore tissue-specific control of the gene
      transcription is likely. In this study we demonstrate that transcription of the
      plasma prekallikrein gene can be initiated at multiple sites, for which at least
      four different promoters are utilized. A comparison of the genomic and mRNA
      sequences of mouse plasma prekallikrein revealed that the sequence segment that
      was formerly regarded as the first exon of the mouse plasma prekallikrein gene
      consists of three exons, with the first exon localized 14.2 kbp upstream of the
      translation start. For the rat and human plasma prekallikrein genes, in silico
      analysis suggested an analogous exon-intron organization. Determination of the
      transcription start sites showed that in both mouse and human, the proximal and
      distal regions could be utilized for transcription initiation; however, the
      proximal region is preferred. A deletion mutation analysis of the proximal
      promoter region using a 1.7-kbp segment revealed a strong activating region
      immediately upstream of the known mRNA, followed by both a modest repressor and
      an enhancer region.

PMID- 15843154
TI  - Enthalpy measurement using calorimetry shows a significant difference in
      potential energy between the active and latent conformations of PAI-1.
AB  - A central feature of the serpin inhibition mechanism is insertion of the reactive
      center loop into the central beta-sheet (beta-sheet A). This insertion also
      occurs when the reactive center loop is cleaved without protease inhibition.
      Using this effect, we have measured the enthalpy (DeltaH) of loop cleavage and
      insertion for plasminogen activator inhibitor 1 (PAI-1) as -38 kcal/mol. Because
      loop insertion can be blocked by incorporating a peptide into the central beta
      sheet, it was possible to assign -7 kcal/mol to loop cleavage and -31 kcal/mol to
      loop insertion. These values are lower than values reported for the serpins alpha
      1 -proteinase inhibitor and antithrombin of -53 to -63 kcal/mol, respectively,
      for loop insertion with negligible enthalpy for loop cleavage. A free energy
      difference of -9 kcal/mol has been reported between the active and spontaneously
      loop inserted "latent forms" of PAI-1, which is significantly smaller in
      magnitude than the -31 kcal/mol of enthalpy we measured for loop insertion.
      Because the enthalpy should relate closely to those regions of PAI-1 that have
      moved to lower potential energy, a difference distance matrix is presented that
      identifies regions of PAI-1 that move during loop insertion.

PMID- 15843155
TI  - Structural metal dependency of the arginase from the human malaria parasite
      Plasmodium falciparum.
AB  - The human malaria parasite Plasmodium falciparum possesses a single gene with
      high similarity to the metalloproteins arginase and agmatinase. The recombinant
      protein reveals strict specificity for arginine, and it has been proposed that
      its function in ornithine production is as a precursor for polyamine
      biosynthesis. The specific activity of the plasmodial arginase was found to be 31
      micromol min(-1) mg(-1) protein and the k(cat) was calculated as 96 (s-1) . The
      Km value for arginine and Ki value for ornithine were determined as 13 mM and 19
      mM, respectively. The active arginase is a homotrimer of ca. 160 kDa. Dialysis of
      the arginase against EDTA results in monomers of approximately 48 kDa; however,
      the quaternary structure can be restored by addition of Mn 2+ . Mutagenic
      analyses of all the amino acid residues proposed to be involved in metal binding
      led to complex dissociation, except for the His-193-Ala mutant, which was also
      inactive but retained the trimeric structure. Substitution of His-233, which has
      been suggested to be in charge of proton shuttling within the active site,
      disrupted the trimeric structure and thereby the activity of the Pf arginase.
      Northern blot analysis identified a stage-specific expression pattern of the
      plasmodial arginase in the ring/young trophozoite stage, which guarantees the
      provision of ornithine for essential polyamine biosynthesis.

PMID- 15843156
TI  - Pre-steady-state kinetic analysis of riboflavin synthase using a pentacyclic
      reaction intermediate as substrate.
AB  - Riboflavin synthase catalyses a mechanistically complex dismutation affording
      riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H )-pyrimidinedione from 6,7
      dimethyl-8-ribityllumazine. A pentacyclic adduct (compound 2 ) of two substrate
      molecules was used as substrate for pre-steady-state kinetic analysis. Whereas
      the wild-type enzyme catalyses the decomposition of compound 2 into a mixture of
      riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H )-pyrimidinedione, as well as
      into two equivalents of 6,7-dimethyl-8-ribityllumazine, a H102Q mutant enzyme
      predominantly catalyses the former reaction. Stopped-flow experiments with this
      mutant enzyme failed to identify a reaction intermediate between compound 2 and
      riboflavin. However, the apparent rate constants for the formation of riboflavin
      as observed by stopped-flow and quenched-flow experiments were significantly
      different, thus suggesting that the reaction proceeds via a significantly
      populated intermediate, the absorbance of which is similar to that of compound 2
      . An F2A mutant enzyme converts compound 2 predominantly into 6,7-dimethyl-8
      ribityllumazine. Stopped-flow experiments using compound 2 as substrate indicated
      a slight and rapid initial increase in absorbance at 310 nm, followed by a slower
      decrease. This finding, in conjunction with different apparent rates for the
      formation of 6,7-dimethyl-8-ribityllumazine, suggests the involvement of a
      significantly populated intermediate in the transition between compound 2 and 6,7
      dimethyl-8-ribityllumazine, the optical spectrum of which is similar to that of
      compound 1.

PMID- 15843157
TI  - Lactoferrampin, an antimicrobial peptide of bovine lactoferrin, exerts its
      candidacidal activity by a cluster of positively charged residues at the C
      terminus in combination with a helix-facilitating N-terminal part.
AB  - The antimicrobial activity of bovine lactoferrin (bLF) is attributed to
      lactoferricin, which is situated in the N1-domain of bLF. Recently, another
      antimicrobial domain consisting of residues 268-284, designated lactoferrampin
      (LFampin), has been identified in the N1-domain of bLF, which exhibited
      antimicrobial activity against Candida albicans and several bacteria. In the
      present study, the candidacidal activity of a series of peptides spanning this
      antimicrobial domain was investigated in relation to the charge and the capacity
      to form a helical conformation in hydrophobic environments. C-Terminal truncation
      of LFampin resulted in a drastic decrease in candidacidal activity. Positively
      charged residues clustered at the C-terminal side of the LFampin domain appeared
      to be crucial for the candidacidal activity. The ability to adopt helical
      conformations did not change when LFampin was truncated at the C-terminal side. N
      Terminally truncated LFampin peptides, truncated up to the sequence 270-284, were
      more reluctant to adopt a helical conformation. Therefore, we conclude that the C
      terminal part of LFampin 265-284, which is the most active peptide, is crucial
      for its candidacidal activity, due to the presence of clustered positive charges,
      and that the N-terminal part is essential for activity as it facilitates helix
      formation.

PMID- 15843158
TI  - Expression and characterization of Rab38, a new member of the Rab small G protein
      family.
AB  - Rab38 is a new member of the Rab small G protein family that regulates
      intracellular vesicle trafficking. Rab38 is expressed in melanocytes and it has
      been clarified that a point mutation in the postulated GTP-binding domain of
      Rab38 is the gene responsible for oculocutaneous albinism in chocolate mice.
      However, basic information regarding recombinant protein production,
      intracellular location, and tissue-specific expression pattern has not yet been
      reported. We produced recombinant Rab38 using a baculovirus/insect cell-protein
      expression system. A combination of Triton X-114 phase separation and nickel
      affinity chromatography yielded exclusively prenylated Rab38 that bound [alpha
      32P]-GTP. The mRNA and the native protein were expressed in a tissue-specific
      manner, e.g., in the lung, skin, stomach, liver, and kidney. Freshly isolated rat
      alveolar type II cells were highly positive for the mRNA signal, but the signal
      was rapidly lost over time. Immunofluorescence staining demonstrated that
      expressed GST-tagged Rab38 was mainly co-localized with endoplasmic reticulum
      resident protein and also partly with intermittent vesicles between the
      endoplasmic reticulum and the Golgi complex. These results indicate that Rab38 is
      expressed non-ubiquitously in specific tissues and regulates early vesicle
      transport relating to the endoplasmic reticulum, and hence suggest that Rab38
      abnormality may cause multiple organ diseases as well as oculocutaneous albinism.

PMID- 15843159
TI  - Trafficking pathways of Cx49-GFP in living mammalian cells.
AB  - In the present study we examined the trafficking pathways of connexin49 (Cx49)
      fused to green fluorescent protein (GFP) in polar and non-polar cell lines. The
      Cx49 gene was isolated from ovine lens by RT-PCR. Cx49 cDNA was fused to GFP and
      the hybrid cDNA was transfected into several cell lines. After transfection of
      Cx49-GFP cDNA into HeLa cells, it was shown using the double whole-cell patch
      clamp technique that the expressed fusion protein was still able to form
      conducting gap junction channels. Synthesis, assembly, and turnover of the Cx49
      GFP hybrid protein were investigated using a pulse-chase protocol. A major 78-kDa
      protein band corresponding to Cx49-GFP could be detected with a turnover of 16-20
      h and a half-life time of 10 h. The trafficking pathways of Cx49-GFP were
      monitored by confocal laser microscopy. Fusion proteins were localized in
      subcellular compartments, including the endoplasmic reticulum (ER), the ER-Golgi
      intermediate compartment, the Golgi apparatus, and the trans-Golgi network, as
      well as vesicles traveling towards the plasma membrane. Time-dependent sequential
      localization of Cx49-GFP in the ER and then the Golgi apparatus supports the
      notion of a slow turnover of Cx49-GFP compared to other connexins analyzed so
      far. Gap junction plaques resembling the usual punctuate distribution pattern
      could be demonstrated for COS-1 and MDCK cells. Basolateral distribution of Cx49
      GFP was observed in polar MDCK cells, indicating specific sorting behavior of
      Cx49 in polarized cells. Together, this report describes the first
      characterization of biosynthesis and trafficking of lens Cx49.

PMID- 15843160
TI  - Ceramides induce programmed cell death in Arabidopsis cells in a calcium
      dependent manner.
AB  - While the role of C2-ceramide in the induction of programmed cell death (PCD) in
      animal systems has been well documented, little is known of its role in plant
      cells. Here we show that C2-ceramide induces PCD in Arabidopsis suspension
      cultures, which is preceded by the generation of a calcium transient and an
      increase in reactive oxygen species (ROS). Inhibition of the calcium transient
      prevented cell death, whereas inhibition of ROS had no effect on cell survival.
      These observations suggest that calcium signalling plays a role in ceramide
      induced PCD but is independent of the generation of ROS.

PMID- 15843161
TI  - Morphology and transfection study of human microvascular endothelial cell
      angiogenesis: an in vitro three-dimensional model.
AB  - Microvascular endothelial cells from human neonatal foreskin were grown in vitro
      until a three-dimensional network of capillary-like structures was formed. All
      stages of the angiogenic cascade could be observed in this in vitro model,
      including the formation of an internal lumen. The microscopy focused on
      morphology, formation of an internal lumen, role of the extracellular matrix,
      polarity of the cells, and the time-course of the angiogenic cascade. Bright
      field microscopy revealed cells arranged circularly side by side and the internal
      lumen of capillary-like structures was verified by electron microscopy.
      Immunolabeling revealed a peritubular localization of collagen IV. Reporter gene
      expression after the formation of capillary-like structures was marginally higher
      than control expression, but clearly lower than the expression of cells at the
      stage of proliferation. Highest transfection efficiencies were obtained using
      vectors with the CMV promoter and the long fragment of the Ets-1 promoter. This
      is a first study of transfection efficiencies mapped for stages of in vitro
      angiogenesis. We describe here the morphological features of a long-term in vitro
      model of angiogenesis of human microvascular endothelial cells that could be used
      for transfection studies, without the provision of an extracellular matrix
      substrate. The cells self-create their own extracellular matrix to proliferate
      and form a three-dimensional network of capillary-like structures with an
      internal lumen.

PMID- 15843162
TI  - Purification and characterisation of blarinasin, a new tissue kallikrein-like
      protease from the short-tailed shrew Blarina brevicauda: comparative studies with
      blarina toxin.
AB  - A new tissue kallikrein-like protease, blarinasin, has been purified from the
      salivary glands of the short-tailed shrew Blarina brevicauda. Blarinasin is a 32
      kDa N-glycosylated protease with isoelectric values ranging between 5.3 and 5.7,
      and an optimum pH of 8.5 for enzyme activity. The cloned blarinasin cDNA coded
      for a pre-pro-sequence and a mature peptide of 252 amino acids with a catalytic
      triad typical for serine proteases and 43.7-54.0% identity to other mammalian
      tissue kallikreins. Blarinasin preferentially hydrolysed Pro-Phe-Arg-4
      methylcoumaryl-7-amide (MCA) and N-tert-butyloxycarbonyl-Val-Leu-Lys-MCA, and
      preferentially converted human high-molecular-weight kininogen (HK) to
      bradykinin. The activity of blarinasin was prominently inhibited by aprotinin
      (K(i) =3.4 nM). A similar kallikrein-like protease, the lethal venom blarina
      toxin, has previously been purified from the salivary glands of the shrew Blarina
      and shows 67.9% identity to blarinasin. However, blarinasin was not toxic in
      mice. Blarinasin is a very abundant kallikrein-like protease and represents 70
      75% of kallikrein-like enzymes in the salivary gland of B. brevicauda.

PMID- 15843163
TI  - Interfering with hepatitis C virus IRES activity using RNA molecules identified
      by a novel in vitro selection method.
AB  - Hepatitis C virus (HCV) infection is one of the world's major health problems,
      and the identification of efficient HCV inhibitors is a major goal. Here we
      report the isolation of efficient anti-HCV internal ribosome entry site (IRES)
      RNA molecules identified by a new in vitro selection method. The newly developed
      procedure consists of two sequential steps that use distinct criteria for
      selection: selection for binding and selection for cleaving. The selection
      protocol was applied to a population of more than 10(15) variants of an anti
      hepatitis C virus ribozyme covalently linked to an aptamer motif. The ribozyme
      was directed against positions 357 to 369 of the HCV IRES, and the cleavage
      substrate was a 691-nucleotide-long RNA fragment that comprises the entire HCV
      IRES domain. After six selection cycles, seven groups of RNA variants were
      identified. A representative of each group was tested for its capacity to inhibit
      IRES activity using in vitro translation assays. All selected RNAs promoted
      significant inhibition, some by as much as 95%.

PMID- 15843165
TI  - Oncogenic Ras in tumour progression and metastasis.
AB  - The ras genes give rise to a family of related GTP-binding proteins that exhibit
      potent transforming potential. Mutational activation of Ras proteins promotes
      oncogenesis by disturbing a multitude of cellular processes, such as gene
      expression, cell cycle progression and cell proliferation, as well as cell
      survival, and cell migration. Ras signalling pathways are well known for their
      involvement in tumour initiation, but less is known about their contribution to
      invasion and metastasis. This review summarises the role and mechanisms of Ras
      signalling, especially the role of the Ras effector cascade Raf/MEK/ERK, as well
      as the phosphatidylinositol 3-kinase/Akt pathway in Ras-mediated transformation
      and tumour progression. In addition, it discusses the impact of Rho GTPases on
      Ras-mediated transformation and metastasis.

PMID- 15843166
TI  - Phosphoinositide 3-kinase signaling in the cellular response to oxidative stress.
AB  - Oxidative stress is linked to the pathogenesis and pathobiochemistry of various
      diseases, including cancer, diabetes and cardiovascular disorders. The non
      specific damaging effect of reactive oxygen species (ROS) generated during
      oxidative stress is involved in the development of diseases, as well as the
      activation of specific signaling cascades in cells exposed to the higher oxidant
      load. A cellular signaling cascade that is activated by several types of reactive
      oxygen species is the phosphoinositide 3'-kinase (PI 3-kinase)/protein kinase B
      (PKB) pathway, which regulates cellular survival and fuel metabolism, thus
      establishing a link between oxidative stress and signaling in neoplastic,
      metabolic or degenerative diseases. Several links of PI 3-kinase/PKB signaling to
      ROS are discussed in this review, with particular focus on the molecular
      mechanisms involved in the regulation of PI 3-kinase signaling by oxidative
      stress and important players such as (i) the glutathione and glutaredoxin system,
      (ii) the thioredoxin system and (iii) Ser/Thr- and Tyr phosphatases.

PMID- 15843167
TI  - Doxorubicin induces EGF receptor-dependent downregulation of gap junctional
      intercellular communication in rat liver epithelial cells.
AB  - Exposure of rat liver epithelial cells to doxorubicin, an anthraquinone
      derivative widely employed in cancer chemotherapy, led to a dose-dependent
      decrease in gap junctional intercellular communication (GJC). Gap junctions are
      clusters of inter-cellular channels consisting of connexins, the major connexin
      in the cells used being connexin-43 (Cx43). Doxorubicin-induced loss of GJC was
      mediated by activation of extracellular signal-regulated kinase (ERK)-1 and ERK
      2, as demonstrated using inhibitors of ERK activation. Furthermore, activation of
      the epidermal growth factor (EGF) receptor by doxorubicin was responsible for ERK
      activation and the subsequent attenuation of GJC. Inhibition of GJC, however, was
      not by direct phosphorylation of Cx43 by ERK-1/2, whereas menadione, a 1,4
      naphthoquinone derivative that was previously demonstrated to activate the same
      EGF receptor-dependent pathway as doxorubicin, resulting in downregulation of
      GJC, caused strong phos-phorylation of Cx43 at serines 279 and 282. Thus, ERK
      dependent downregulation of GJC upon exposure to quinones may occur both by
      direct phosphorylation of Cx43 and in a phosphorylation-independent manner.

PMID- 15843168
TI  - TGF beta-induced focal complex formation in epithelial cells is mediated by
      activated ERK and JNK MAP kinases and is independent of Smad4.
AB  - Advanced malignancies often exhibit increased concentrations of transforming
      growth factor-beta (TGF beta), which has been suggested to promote invasion and
      metastasis. While inhibition of epithelial cell proliferation in response to TGF
      beta is mainly mediated by the well-characterised Smad pathway, the molecular
      mechanism leading to TGF beta-induced invasiveness and metastasis are largely
      unknown. To elucidate these mechanisms, we compared TGF beta1 signalling in MCF-7
      and the Smad4-negative MDA-MB-468 breast cancer cells. Both cell lines react to
      TGF beta1 treatment with decreased subcortical actin and increased numbers of
      focal contacts. TGF beta1-induced cell migration was strongly dependent on the
      activation of extracellular signal-regulated kinase (ERK) and Jun N-terminal
      kinase (JNK). These mitogen-activated protein kinases were phosphorylated in
      response to TGF beta and subsequently translocated into focal contacts.
      Inhibition of the TGF beta type I receptor ALK5 slightly reduced phosphorylation
      of ERK in MCF-7 cells, but neither inhibited phosphorylation of ERK in MDA-MB-468
      cells nor TGF beta1-induced migration of both cell lines. In contrast, ALK5
      inhibition effectively blocked Smad2 phosphorylation. In addition to ERK and JNK,
      the monomeric GTPase RhoA was activated by TGF beta1 and necessary for TGF beta
      induced migration. Taken together, our study identifies a role of ERK and JNK
      activation and association of activated MAPKs with focal complexes in TGF beta1
      induced cell migration in epithelial cells. These TGF beta-dependent processes
      were mediated independently of Smad4.

PMID- 15843169
TI  - On the mechanism of alkylphosphocholine (APC)-induced apoptosis in tumour cells.
AB  - Alkylphosphocholines (APCs) represent a new and very encouraging class of
      antitumour agents that have also been shown to induce apoptosis in tumour cells,
      but their exact mode of action has still not been elucidated. The APC compound
      presented here, S-1-O-phosphocholine-2- N-acetyl-octadecane (S-NC-2) induces
      apoptosis in a variety of cancer cells. To define the molecular requirements for
      S-NC-2-induced apoptosis, activation of caspase-8 and -3 and the cleavage of
      death substrates, such as poly(ADP-ribose) polymerase (PARP), were investigated
      in Jurkat, BJAB, SKW6.4 and K562 cells. The signalling pathway seems to be
      initiated at the death receptor level. Cells that are defective in Fas-receptor
      signalling (e.g., FADDdn BJAB), as well as cells lacking the Fas receptor (K562),
      were resistant to S-NC-2 treatment. Furthermore, the treatment of Jurkat cells
      with S-NC-2 resulted in the clustering of death receptor molecules and co
      localisation of the Fas receptor with caveolin, a marker for lipid rafts. In
      addition, the involvement of mitochondria was detected, since S-NC-2 induces the
      breakdown of the mitochondrial membrane potential. Overexpression of the anti
      apoptotic protein Bcl-2 prevented the loss of delta psi(m) in type II (Jurkat)
      but not in type I cells (SKW6.4). Moreover, cleavage of Bid was found, which
      points to a possible linkage between the receptor-dependent and the mitochondrial
      pathways.

PMID- 15843170
TI  - Self-organization versus Watchmaker: stochastic dynamics of cellular
      organization.
AB  - The cell, as a molecular system, is often interpreted in terms of complex
      clockworks, and the design charts of mechanical and electrical engineering are
      assumed to provide adequate approximations for the description of cellular
      organization. However, a growing body of experimental evidence obtained through
      the observation and analysis of real-time dynamics of fluorescently labeled
      molecules inside living cells is increasingly inconsistent with the classico
      mechanistic perception of the cell. An overview of recent studies favors an
      emerging alternative image of the cell as a dynamic integrated system of
      interconnected and interdependent metastable molecular organizations realized
      through stochasticity and self-organization.

PMID- 15843171
TI  - Varicella-zoster virus IE63 protein represses the basal transcription machinery
      by disorganizing the pre-initiation complex.
AB  - Using transient transfection assays, regulation properties of varicella-zoster
      virus (VZV)-encoded IE63 protein were analyzed on several VZV immediate early
      (ORF4), early (ORF28) and late (ORF67) promoters. IE63 was shown to repress the
      basal activity of most of the promoters tested in epithelial (Vero) and neuronal
      (ND7) cells to various extents. Trans-repressing activities were also observed on
      heterologous viral and cellular promoters. Since a construct carrying only a TATA
      box sequence and a series of wild-type or mutated interleukin (IL)-8 promoters
      was also repressed by IE63, the role of upstream regulatory elements was ruled
      out. Importantly, the basal activity of a TATA-less promoter was not affected by
      IE63. Using a series of IE63 deletion constructs, amino acids 151-213 were shown
      to be essential to the trans-repressing activity in Vero cells, while in ND7
      cells the essential region extended to a much larger carboxy-terminal part of the
      protein. We also demonstrate that IE63 is capable of disrupting the
      transcriptional pre-initiation complex and of interacting with several general
      transcription factors. The central and carboxy-terminal domains of IE63 are
      important for these effects. Altogether, these results demonstrate that IE63
      protein is a transcriptional repressor whose activity is directed towards general
      transcription factors.

PMID- 15843172
TI  - Trehalose and 6-aminohexanoic acid stabilize and renature glucose-6-phosphate
      dehydrogenase inactivated by glycation and by guanidinium hydrochloride.
AB  - A number of naturally occurring small organic molecules, primarily involved in
      maintaining osmotic pressure in the cell, display chaperone-like activity,
      stabilizing the native conformation of proteins and protecting them from various
      kinds of stress. Most of them are sugars, polyols, amino acids or methylamines.
      In addition to their intrinsic protein-stabilizing activity, these small organic
      stress molecules regulate the activity of some molecular chaperones, and may
      stabilize the folded state of proteins involved in unfolding or in misfolding
      diseases, such as Alzheimer's and Parkinson's diseases, or alpha1-antitrypsin
      deficiency and cystic fibrosis, respectively. Similar to molecular chaperones,
      most of these compounds have no substrate specificity, but some specifically
      stabilize certain proteins, e.g., 6-aminohexanoic acid (AHA) stabilizes
      apolipoprotein A. In the present work, the capacity of 6-aminohexanoic acid to
      stabilize non-specifically other proteins is demonstrated. Both trehalose and AHA
      significantly protect glucose-6-phosphate dehydrogenase (G6PD) against glycation
      induced inactivation, and renatured enzyme already inactivated by glycation and
      by guanidinium hydrochloride (GuHCl). To the best of our knowledge, there are no
      data on the effect of these compounds on protein glycation. The correlation
      between the recovery of enzyme activity and structural changes indicated by
      fluorescence spectroscopy and Western blotting contribute to better understanding
      of the protein stabilization mechanism.

PMID- 15843173
TI  - Quercetin metabolism in vital and apoptotic human leukaemia cells.
AB  - The metabolism of the flavonol quercetin in human leukaemia (HL-60) cells was
      investigated. The fluorescence that is elicited by quercetin upon binding to a
      target protein was quickly attenuated in vital cells, while apoptotic cells
      showed persistent fluorescence. The dynamics of induction and loss of
      fluorescence in the cells were quantified by flow cytometry. Several potential
      metabolites of quercetin, apart from isorhamnetin, had weak or no fluorogenic
      properties with test proteins. HPLC analysis showed that quercetin was
      metabolised to several substances, among them glycosylated metabolites. The loss
      of fluorescence in vital cells offers the unique opportunity to directly observe
      the metabolic conversion of quercetin in human cells.

PMID- 15843174
TI  - One of the Ca2+ binding sites of recoverin exclusively controls interaction with
      rhodopsin kinase.
AB  - Recoverin is a neuronal calcium sensor protein that controls the activity of
      rhodopsin kinase in a Ca(2+)-dependent manner. Mutations in the EF-hand Ca2+
      binding sites are valuable tools for investigating the functional properties of
      recoverin. In the recoverin mutant E121Q (Rec E121Q ) the high-affinity Ca2+
      binding site is disabled. The non-myristoylated form of Rec E121Q binds one Ca2+
      via its second Ca(2+)-binding site (EF-hand 2), whereas the myristoylated variant
      does not bind Ca2+ at all. Binding of Ca2+ to non-myristoylated Rec E121Q
      apparently triggers exposure of apolar side chains, allowing for association with
      hydrophobic matrices. Likewise, an interaction surface for the recoverin target
      rhodopsin kinase is constituted upon Ca2+ binding to the non-acylated mutant.
      Structural changes resulting from Ca(2+)-occupation of EF-hand 2 in myristoylated
      and non-myristoylated recoverin variants are discussed in terms of critical
      conditions required for biological activity.

PMID- 15843175
TI  - Enzymatic profiling of human kallikrein 14 using phage-display substrate
      technology.
AB  - The human KLK14 gene is one of the newly identified serine protease genes
      belonging to the human kallikrein family, which contains 15 members. KLK14 , like
      all other members of the human kallikrein family, is predicted to encode for a
      secreted serine protease already found in various biological fluids. This new
      kallikrein is mainly expressed in prostate and endocrine tissues, but its
      function is still unknown. Recent studies have demonstrated that KLK14 gene
      expression is up-regulated in prostate and breast cancer tissues, and that higher
      expression levels correlate with more aggressive tumors. In this work, we used
      phage-display substrate technology to study the substrate specificity of hK14. A
      phage-displayed random pentapeptide library with exhaustive diversity was
      screened with purified recombinant hK14. Highly specific and sensitive substrates
      were selected from the library. We show that hK14 has dual activity, trypsin- and
      chymotrypsin-like, with a preference for cleavage after arginine residues. A
      SwissProt database search with selected sequences identified six potential human
      protein substrates for hK14. Two of them, laminin alpha-5 and collagen IV, which
      are major components of the extracellular matrix, have been demonstrated to be
      hydrolyzed efficiently by hK14.

PMID- 15843176
TI  - A new selective substrate for cathepsin E based on the cleavage site sequence of
      alpha2-macroglobulin.
AB  - Cathepsin E is an intracellular aspartic proteinase of the pepsin family
      predominantly expressed in cells of the immune system and believed to contribute
      to homeostasis by participating in host defense mechanisms. Studies on its
      enzymatic properties, however, have been limited by a lack of sensitive and
      selective substrates. For a better understanding of the importance of this enzyme
      in vivo, we designed and synthesized a highly sensitive peptide substrate for
      cathepsin E based on the sequence of the specific cleavage site of alpha2
      macroglobulin. The substrate constructed, MOCAc-Gly-Ser-Pro-Ala-Phe-Leu-Ala
      Lys(Dnp)-D-Arg-NH2 [where MOCAc is (7-methoxycoumarin-4-yl)acetyl and Dnp is
      dinitrophenyl], derived from the cleavage site sequence of human alpha2
      macroglobulin, was the most sensitive and selective for cathepsin E, with
      k(cat)/K(m) values of 8-11 microM(-1) s(-1), whereas it was resistant to
      hydrolysis by the analogous aspartic proteinases cathepsin D and pepsin, as well
      as the lysosomal cysteine proteinases cathepsins B, L, and H. The assay allows
      the detection of a few fmol of cathepsin E, even in the presence of plasma and
      cell lysate, and gives accurate results over a wide enzyme concentration range.
      This substrate might represent a useful tool for monitoring and accurately
      quantifying cathepsin E, even in crude enzyme preparations.

PMID- 15843177
TI  - Contributions of Dr. William C. Menninger to military psychiatry.
AB  - This review of the contributions of Dr. William C. Menninger to military
      psychiatry includes: (1) a brief biography with particular reference to Dr.
      Will's work with the military in World War II; (2) the status of psychiatry in
      the Army in 1944 at the time Dr. Will was appointed to head psychiatry in the
      Army; (3) Dr. Will's discussion of the characteristics of an effective military
      psychiatrist; (4) psychiatric treatment in combat situations as it evolved in
      World War II; (5) the concept of prevention, which Dr. Will felt was critically
      important; (6) a summary of Dr. Will's experience in World II; and (7)
      reflections from Dr. Will's colleagues.

PMID- 15843178
TI  - Suicide and awareness of illness in schizophrenia: an overview.
AB  - Suicide is the first cause of premature death in patients with schizophrenia.
      Numerous studies have identified risk factors for suicide among these patients.
      This study reviews available literature focusing on awareness of illness in
      patients with schizophrenia. Insight, or awareness of illness, has been
      considered a risk factor for suicide in schizophrenic patients. In assessing
      insight, many issues have to be taken into account, because a high degree of
      insight is not desirable in some conditions.

PMID- 15843179
TI  - Psychobiological dysregulation in violence-exposed mothers: salivary cortisol of
      mothers with very young children pre- and post-separation stress.
AB  - To understand the determinants of frightening/frightened and other atypical
      maternal behavior, the authors studied a sample of 41 inner-city mothers of very
      young children (ages 8-50 months), the mothers of whom had lifetime histories of
      interpersonal violent trauma (i.e., physical or sexual abuse, and domestic
      violence) and related posttraumatic stress. METHOD: The authors measured (1)
      maternal salivary cortisol levels before and 30 minutes after a videotaped play
      paradigm with their children, involving two separations and reunions; and (2)
      cortisol reactivity 30 minutes after separation stress. Data were analyzed using
      Pearson bivariate correlations, ANOVA, and multiple linear regressions. RESULTS:
      Salivary cortisol "baseline" values were significantly negatively correlated with
      childhood interpersonal violent trauma severity (i.e., trauma severity prior to
      age 16). However, cortisol reactivity was not significantly correlated with
      interpersonal violent trauma severity at this level of analysis. Although
      baseline salivary cortisol values were not significantly correlated with current
      overall psychiatric or depressive symptoms, they were negatively correlated with
      severity of current posttraumatic stress symptoms (PTSS) and with dissociative
      symptoms. Neither dimensions of negativity nor distortion of maternal
      attributions showed any significant association with prestress or poststress
      salivary cortisol levels. Salivary cortisol baseline was negatively correlated
      with atypical maternal behavior via measurement of the level of disrupted
      communication, at a trend-level of significance. CONCLUSIONS: Violent trauma
      associated dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may be
      a marker for increased risk for intergenerational transmission via parenting
      behavior with young children. Low salivary cortisol prior to separation stress
      and blunted cortisol reactivity to separation may also be markers for
      posttraumatic stress.

PMID- 15843180
TI  - A psychoanalytically oriented combined treatment approach for severely disturbed
      borderline patients: the Athens project.
AB  - A psychoanalytically oriented combined treatment is considered beneficial for
      severely disturbed borderline patients, especially during an acute crisis. The
      proposed treatment comprises hospitalization and specialized psychotherapeutic
      inpatient treatment, individual psychoanalytic psychotherapy, and psychiatric
      management. It is important to take into account that during inpatient treatment,
      projective identifications and splitting mechanisms are activated, involving
      different members of the therapeutic personnel or other patients. The mental
      health team--the psychiatrist, the nurses, the assigned psychotherapist, and
      other members of the therapeutic personnel--should work together in the context
      of teamwork in order to explore transference and countertransference
      manifestations. This function promotes empathy and understanding of the patient's
      inner difficulties. A combined treatment approach can help the patient stabilize
      his or her condition and develop awareness and motivation for undertaking long
      term treatment and individual psychoanalytic psychotherapy, with the prospect
      that therapy will be maintained after the patient's discharge.

PMID- 15843203
TI  - Quality control for SELDI analysis.

PMID- 15843204
TI  - Immunobead multiplex RT-PCR detection of carcinoembryonic genes expressing cells
      in the blood of colorectal cancer patients.
AB  - Circulating cell detection using reverse transcriptase-polymerase chain reaction
      (RT-PCR) techniques has been studied as a new prognostic factor in colorectal
      cancer patients. With the view of enhancing detection sensitivity, we developed a
      new multiplex RT-PCR assay for circulating cell detection based on the expression
      of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5; formerly
      CEA) and CEACAM7 (formerly CGM2). Between November 2002 and December 2003, 45
      stage III-IV, 39 stage I-II colorectal cancer patients, 32 non-colorectal cancer
      patients and 41 healthy individuals were included. Positive selection using HEA
      125 immunobeads was applied to blood samples before mRNA extraction, cDNA
      synthesis and a multiplex CEACAM5/CEACAM7 RT-PCR assay. For both CEACAM5 and
      CEACAM7, the limit of detection was found to be as low as 1 expressing cell in
      10(6) nucleated blood cells. The multiplex RT-PCR assay was negative for the 41
      healthy individuals and the 32 non-colorectal cancer patients. The test was
      positive in 53/84 (63%) of the colorectal cancer patients for CEACAM5 and/or
      CEACAM7, whereas 32/84 (38%) were positive for both markers. Colorectal cancer
      patients were positive for one of the two markers in 80% of cases (36/45) for
      stage III-IV patients (CEACAM5 73%, CEACAM7 51%) and in 44% of cases (17/39) for
      stage I-II patients. This multiplex RT-PCR assay with two markers proved to be
      more sensitive than use of a single marker in detecting circulating tumour cells.
      The discrepant expression of CEACAM5 and CEACAM7 may label circulating tumour
      cells that have different levels of differentiation and subsequent aggressive
      behaviour.

PMID- 15843205
TI  - Optimization and evaluation of surface-enhanced laser desorption/ionization time
      of-flight mass spectrometry (SELDI-TOF MS) with reversed-phase protein arrays for
      protein profiling.
AB  - Surface-enhanced laser desorption/ionization (SELDI) time-of-flight mass
      spectrometry with protein arrays has facilitated the discovery of disease
      specific protein profiles in serum. Such results raise hopes that protein
      profiles may become a powerful diagnostic tool. To this end, reliable and
      reproducible protein profiles need to be generated from many samples, accurate
      mass peak heights are necessary, and the experimental variation of the profiles
      must be known. We adapted the entire processing of protein arrays to a robotics
      system, thus improving the intra-assay coefficients of variation (CVs) from 45.1%
      to 27.8% (p<0.001). In addition, we assessed up to 16 technical replicates, and
      demonstrated that analysis of 2-4 replicates significantly increases the
      reliability of the protein profiles. A recent report on limited long-term
      reproducibility seemed to concord with our initial inter-assay CVs, which varied
      widely and reached up to 56.7%. However, we discovered that the inter-assay CV is
      strongly dependent on the drying time before application of the matrix molecule.
      Therefore, we devised a standardized drying process and demonstrated that our
      optimized SELDI procedure generates reliable and long-term reproducible protein
      profiles with CVs ranging from 25.7% to 32.6%, depending on the signal-to-noise
      ratio threshold used.

PMID- 15843206
TI  - Simultaneous determination of HIV antibodies, hepatitis C antibodies, and
      hepatitis B antigens in dried blood spots--a feasibility study using a multi
      analyte immunoassay.
AB  - HIV in particular, as well as hepatitis B and C, present a burden on healthcare
      systems worldwide. Early detection of these diseases may prevent further
      infections and improve the outcome for patients. In particular, transmission of
      HIV from mother to child can be significantly reduced when preventive measures
      are taken before birth. We have developed and optimized a method for the
      simultaneous detection of HIV 1 and hepatitis B and C from dried blood specimens
      using the Luminex multi-analyte profiling technology (LabMap). Dried blood spots
      provide a convenient method for mailing, analysis and storage of samples.
      Specimens from known HIV-positive children (n=46) as well as hepatitis B- (n=8)
      and hepatitis C-positive patients (n=7) tested positive in our assay. Storage for
      up to 10 years did not interfere with the test in the case of HIV-positive
      patients. Results for five different antibodies and one antigen were obtained in
      approximately 80 seconds. Furthermore, antibody levels in infants of HIV-positive
      mothers were monitored over a period of 1 year. Antibodies were no longer
      detectable after 260-360 days, which compared well with results independently
      obtained by ELISA and Western blot analysis. We demonstrated the feasibility of
      the simultaneous detection of infectious diseases from dried blood. Our novel
      method also provides a convenient tool for monitoring children from HIV-positive
      mothers and for possible screening efforts.

PMID- 15843207
TI  - Hematopoietic cytokines in the sera of patients with pancreatic cancer.
AB  - Hematopoietic cytokines (HCs) can affect the growth and spread of cancer.
      Therefore, in the present study, we investigated in pancreatic cancer patients
      the serum levels of selected HCs, such as stem cell factor (SCF), interleukin 3
      (IL-3), granulocyte-macrophage-colony stimulating factor (GM-CSF), granulocyte
      colony stimulating factor (G-CSF) and macrophage-colony stimulating factor (M
      CSF) in relation to a control group and to a group of patients with chronic
      pancreatitis. Classical tumor markers such as carcinoembryonic antigen (CEA) and
      carbohydrate antigen 19-9 (CA 19-9) were also tested. We compared the serum level
      of cytokines with the tumor stage. The diagnostic sensitivity, specificity,
      positive and negative predictive values and receiver-operating characteristics
      (ROC) curve for cytokines and classical tumor markers were defined. The cytokines
      were measured in 48 patients with pancreatic cancer, in 23 patients with chronic
      pancreatitis and in 40 healthy subjects. HCs were determined using ELISA. CEA and
      CA 19-9 were measured by microparticle enzyme immunoassay. There were significant
      differences in the levels of circulating SCF, IL-3, GM-CSF, M-CSF, CEA and CA 19
      9 in the pancreatic cancer patients compared to the control group. The serum
      levels of M-CSF and tumor markers were significantly higher in pancreatic cancer
      patients compared to the pancreatitis group. The levels of SCF, M-CSF and tumor
      markers were higher in patients with a more advanced tumor stage. The M-CSF serum
      levels in the pancreatitis group correlated positively with the tumor markers
      tested--CEA and CA 19-9. The diagnostic sensitivity of SCF and specificity of M
      CSF and tumor markers were the highest. The SCF and M-CSF areas under the ROC
      curve were greater than the areas for other cytokines. These results suggest the
      potential usefulness of HCs in pancreatic cancer detection; however, further
      investigations of early-stage pancreatic cancer patients and confirmation by a
      prospective study are necessary.

PMID- 15843208
TI  - Modulation of translation factor's gene expression by histone deacetylase
      inhibitors in breast cancer cells.
AB  - The histone deacetylase inhibitors sodium butyrate (NaBu) and trichostatin A
      (TSA) exhibit anti-proliferative activity by causing cell cycle arrest and
      apoptosis. The mechanisms by which NaBu and TSA cause apoptosis and cell cycle
      arrest are not yet completely clarified, although these agents are known to
      modulate the expression of several genes including cell-cycle- and apoptosis
      related genes. The enzymes involved in the process of translation have important
      roles in controlling cell growth and apoptosis, and several of these translation
      factors have been described as having a causal role in the development of cancer.
      The expression patterns of the translation mechanism, namely of the elongation
      factors eEF1A1 and eEF1A2, and of the termination factors eRF1 and eRF3, were
      studied in the breast cancer cell line MCF-7 by real-time quantitative reverse
      transcription-polymerase chain reaction after a 24-h treatment with NaBu and TSA.
      NaBu induced inhibition of translation factors' transcription, whereas TSA caused
      an increase in mRNA levels. Thus, these two agents may modulate the expression of
      translation factors through different pathways. We propose that the inhibition
      caused by NaBu may, in part, be responsible for the cell cycle arrest and
      apoptosis induced by this agent in MCF-7 cells.

PMID- 15843209
TI  - Whole genome amplification of buccal cell DNA: genotyping concordance before and
      after multiple displacement amplification.
AB  - While buccal cells provide an easily accessible source of genomic DNA, the amount
      extracted may be insufficient for many studies. Whole genome amplification (WGA)
      using multiple displacement amplification (MDA) may optimize buccal cell genomic
      DNA yield. We compared the usefulness, in epidemiological surveys, of DNA derived
      from buccal cells collected by alcohol mouthwash and amplified by WGA protocol
      and standard protocols. Buccal cell collection kits were mailed to 300 randomly
      selected members of a large cohort study, and 189 subjects returned buccal cell
      samples. We determined: (i) which QIAamp DNA Blood Mini Kit extraction protocol
      (tissue or blood) produced more DNA; and (ii) whether it is feasible to use MDA
      to prepare DNA for single nucleotide polymorphism (SNP) genotyping of markers
      such as the methylenetetrahydrofolate reductase (MTHFR) and vitamin D receptor
      (VDR) genes. The two DNA extraction protocols were tested on 20 different patient
      samples each. The tissue protocol yielded more DNA than the blood protocol
      (15.4+/-8.6 vs. 7.6+/-7.1 microg, p<0.0001). The 20 DNA samples extracted using
      the tissue protocol were then subjected to pre- and post-MDA genotyping using
      amplicons for the MTHFR SNP at C677T and the intron 8 VDR SNP. No genotyping
      discrepancies were detected in pair-wise comparisons of pre- and post-MDA.
      Genotyping DNA from MDA-based WGA is indistinguishable from routine polymerase
      chain reaction and offers a stable DNA source for genomic research and clinical
      diagnosis.

PMID- 15843210
TI  - Y-chromosome short tandem repeat (STR) haplotypes in a Campania population
      sample.
AB  - Given the lack of information about Y haplotypes for Campania (southern Italy),
      we analyzed eight Y short tandem repeats in a sample of males from this region
      with the aim of establishing a Y-haplotype database that can be used for forensic
      purposes. The eight Y short tandem repeats were amplified by two PCR multiplex
      reactions: multiplex A for loci DYS19, DYS385, DYS392 and DYS393, and multiplex B
      for DYS389 I and II, DYS390, DYS391 and DYS385. The proportion of unique
      haplotypes was 100% (108 Y-chromosome haplotypes in 108 unrelated males) and the
      haplotype diversity discrimination index was 0.99. These data reflect the high
      heterogeneity of male lineage in our population and are similar to those obtained
      in other regions of southern Italy.

PMID- 15843211
TI  - TaqMan assays for genotyping of single nucleotide polymorphisms present at a
      disease susceptibility locus on chromosome 6.
AB  - Multiple single-nucleotide polymorphisms in the BAT1-NFKBIL1-LTA region on the
      short arm of chromosome 6 have been found to be associated with susceptibility to
      myocardial infarction in a recent case-control study including individuals from
      Japan. Specifically, the association relates to homozygosity for the minor
      alleles of five individual polymorphisms (one each in BAT1 and NFKBIL1 and three
      in LTA) and a haplotype defined by a particular allele combination of 10
      polymorphisms (three each in BAT1 and NFKBIL1 and four in LTA). In the Japanese
      study, genotype determinations were carried out using a multiplex PCR-Invader
      assay or DNA sequencing. As an alternative to these methods, we have established
      TaqMan assays for genotyping of nine of the 10 polymorphisms. Accuracy of the
      genotyping results obtained with the TaqMan reactions was demonstrated in
      experiments involving restriction enzyme analysis or DNA sequencing. Using the
      new TaqMan assays, we have genotyped the polymorphisms in a group of 1211
      Caucasians who presented without symptoms or signs of acute or previous
      myocardial infarction. Genotype distributions of each of the five myocardial
      infarction-associated polymorphisms were significantly different between the
      present study group and two Japanese control groups (p < or = 0.01). High linkage
      disequilibrium measures between polymorphisms suggested that the nine
      polymorphisms reside in a single haplotype block. Based on the nine
      polymorphisms, eight different haplotypes with allele frequencies above 1% were
      identified, which together represented 98.4% of the total number of chromosome 6
      in the 1211 individuals. This Caucasian study group and the Japanese sample
      showed strong linkage disequilibrium in the myocardial infarction-associated BAT1
      NFKBIL1-LTA genomic region and related haplotype content, but significantly
      different genotype frequencies. The new TaqMan systems provide relatively simple
      and fast assays to test the clinical relevance of these polymorphisms.

PMID- 15843212
TI  - The secretion of ibuprofen metabolites interferes with the capillary
      chromatography of urinary homovanillic acid and 4-hydroxy-3-methoxymandelic acid
      in neuroblastoma diagnosis.
AB  - Neuroblastoma is the most common extracranial solid tumor in children. Abnormal
      secretion of catecholamines in tissues and body fluids allows for the
      differential diagnosis of neuroblastoma from other neoplasms and its distinction
      from non-neoplastic inflammatory diseases. This is achieved by assaying
      homovanillic acid and 4-hydroxy-3-methoxymandelic acid, the catabolites of
      catecholamine metabolism. In the course of an evaluation of children with
      suspected neuroblastoma, homovanillic acid and 4-hydroxy-3-methoxymandelic acid
      were analyzed in urine samples by capillary gas chromatography with flame
      ionization detection after extraction and derivatization of these compounds as
      trimethylsilyl derivatives. In three urine samples a significant increase in
      biogenic amines was observed, but these results were not confirmed by thin-layer
      chromatography. Patient history revealed that these children had been treated
      with ibuprofen, an analgesic and anti-inflammatory drug. To verify how ibuprofen
      or its metabolites may have interfered with capillary gas chromatography with
      flame ionization detection, we analyzed the same samples by capillary gas
      chromatography-mass spectrometry. In urine samples from patients on the drug, the
      presence of a peak identified as the trimethylsilyl ester of hydroxyibuprofen,
      which had the same retention time as 4-hydroxy-3-methoxymandelic acid, was found
      to interfere with the capillary gas chromatography with flame ionization
      detection analysis of the metabolite. This interference must be taken into
      account during the laboratory diagnosis of neuroblastoma.

PMID- 15843213
TI  - Selective measurement of HCHO in urine using direct liquid-phase fluorimetric
      analysis.
AB  - Quantification of formaldehyde (HCHO) in urine was recently shown to be a
      promising tool in the investigation of cancer, particularly bladder cancer.
      Development of a low-maintenance, inexpensive and rapid analyzer for HCHO in
      urine would greatly facilitate future research and the potential diagnosis of
      bladder cancer. We examine here the application of an off-the-shelf system,
      originally designed for gas-phase atmospheric monitoring of HCHO, for the
      quantification of HCHO in urine. Under strict dietary protocols, e.g., avoidance
      of foods rich in free or chemically bound HCHO, an increase in HCHO in urine is
      an indirect indicator of cancer in the urogenital system. The concentration of
      HCHO in urine samples from an individual over a several-month period was
      determined, with a range from 39 to 1400 microM and a mean of 600 microM. The
      limit of detection for the present method was 0.1 microM. The proposed technique
      provides a direct, low-cost and greatly simplified analytical method for the
      quantification of HCHO in urine compared to other available techniques.

PMID- 15843214
TI  - A spectrophotometric micromethod for determining erythrocyte protoporphyrin-IX in
      whole blood or erythrocytes.
AB  - An increased concentration of erythrocyte protoporphyrin-IX in whole blood or
      erythrocytes is a valuable diagnostic indicator for acquired porphyrias, e.g.,
      iron deficiency anemia and lead poisoning, and for inherited porphyrias. We
      developed a spectrophotometric micromethod for determining erythrocyte
      protoporphyrin-IX. In this method, exhaustive release of erythrocyte porphyrins
      is achieved using hydroquinone and formic acid. The clean-up procedure for 50
      microL of whole blood or erythrocytes covers three steps of liquid/liquid solvent
      partition: two partitions using diethyl and diisopropyl ether and HCl 2.5 mol/L,
      and one buffered step using ammonium formate. Determinations of erythrocyte
      protoporphyrin-IX are possible by: (a) absorption using three wavelengths,
      Rimington's constant and a millimolar absorptivity coefficient m
      epsilon(408.8)=294.3 L x mmol(-1) x cm(-1) according to With; and (b) 2nd
      derivative, which is linked to m epsilon(408.8). Determination of erythrocyte
      protoporphyrin-IX using a 2nd derivative algorithm showed better spectral
      resolution and higher sensitivity at a five-fold lower detection limit compared
      to absorption. Within-run precision of medium and high levels was found for
      absorption and for 2nd derivative with a coefficient of variation (CV) of 1.4
      1.9% (n=10). Total precision evaluated was CV=2.5-8.3% (n=20). Levels of
      reference intervals could only be measured using the 2nd derivative (CV 2.9%).
      Linearity was proved to E=1.0. Recoveries of protoporphyrin-IX ranged from 95.3%
      to 103.0%. Method comparison was carried out using a fluorimetric reference
      method (Piomelli). Reference intervals for gender groups are discussed.

PMID- 15843215
TI  - Simultaneous analysis of MDR1 C3435T, G2677T/A, and C1236T genotypes by
      multiplexed mutagenically separated PCR.
AB  - P-glycoprotein (PGP) encoded by the multi-drug-resistance 1 (MDR1) gene is a
      member of the ATP-binding cassette (ABC) transporter family, drug-transporting
      proteins involved in the bioavailability and pharmacokinetics of various drugs.
      Several single nucleotide polymorphisms (SNPs) in the MDR1 gene have been
      identified so far that may influence PGP expression levels and function. Thus,
      genotyping for MDR1 polymorphisms and determining specific haplotypes may become
      an important tool in predicting individual susceptibility to developing drug
      resistance. We developed a new multiplexed allele-specific PCR method based on
      the principle of mutagenically separated PCR (MS-PCR) for rapid and reliable
      simultaneous genotyping of the C3435T polymorphism in exon 26 of the MDR1 gene
      and two additional SNPs (G2677T/A in exon 21 and C1236T in exon 12), which are in
      linkage disequilibrium with MDR1 C3435T. The accuracy and reliability of this
      method was confirmed by sequencing the respective regions in the MDR1 gene. This
      newly developed MDR1 MS-PCR will facilitate fast, accurate and economic analysis
      of MDR1 genotypes and will provide important information in optimizing individual
      therapeutic approaches.

PMID- 15843216
TI  - Measurement of reticulocyte and red blood cell indices in patients with iron
      deficiency anemia and beta-thalassemia minor.
AB  - New parameters correlated with the hemoglobin content in reticulocytes (RET-Y)
      and in red blood cells (RBC-Y) have been suggested as helpful in diagnosing iron
      deficiency anemia. We have studied RET-Y and RBC-Y indices in two groups of
      patients with microcytosis to verify if these parameters could be used to
      differentiate iron deficiency anemia from beta-thalassemia minor. Blood samples
      from 33 iron-deficient patients, 25 beta-thalassemic minor patients and 50 normal
      individuals were analyzed on a Sysmex XE-2100 instrument. A significant
      difference was observed in reticulocyte counting and immature reticulocyte
      fraction between iron deficiency anemia and beta-thalassemia minor groups, but
      not in RBC-X and RET-Y parameters. Reticulocyte counting was higher in beta
      thalassemia minor and the immature reticulocyte fraction was higher in severe
      iron deficiency anemia. The ratio RET-Y/mean cell volume was tested and was
      significantly different when beta-thalassemia minor was compared with mild and
      severe iron deficiency anemia, and showed better performance than the Mentzer
      ratio and the Green and King function. A great overlap of RET-Y and RBC-Y
      individual values was observed in both groups of microcytic anemias; we conclude
      that these new indices may be used with caution as indicative of iron deficiency,
      mainly in populations where beta-thalassemia minor is frequent.

PMID- 15843217
TI  - Chitotriosidase activity in colostrum from African and Caucasian women.
AB  - Chitotriosidase (ChT), a protein produced by activated macrophages, belongs to
      the chitinases, a group of enzymes able to hydrolyze chitin, a structural
      component of fungi and nematodes. A codominant inherited deficiency in ChT
      activity is frequently reported in plasma of Caucasian subjects, whereas in the
      African population this deficiency is rare. This study compares ChT activity in
      colostrum of 53 African women and 50 Caucasian women. Samples were collected at
      24-48 and 72 h after delivery. We found elevated ChT in colostrum of African
      women on the first day after delivery (1230+/-662 nmol/mL/h) which decreased to
      275+/-235 nmol/mL/h on the third day. The ChT activity on the first day after
      delivery in the colostrum of Caucasian women, however, was significantly lower
      (293+/-74 nmol/mL/h) and decreased to 25+/-20 and 22+/-19 nmol/mL/h on the 2nd
      and 3rd day, respectively. The ChT activity in plasma of African women was also
      higher (101+/-80 nmol/mL/h) than that of Caucasian women (46+/-16 nmol/mL/h), but
      no correlation was found between plasma and colostrum ChT activity. The elevated
      ChT activity in colostrum of African women suggests the presence of activated
      macrophages in human milk, consistent with the genetic characteristics of the
      African population.

PMID- 15843218
TI  - Integration between point-of-care cardiac markers in an emergency/cardiology
      department and the central laboratory: methodological and preliminary clinical
      evaluation.
AB  - To achieve rapid assessment of chest pain in emergency/cardiology departments, a
      short turnaround time for cardiac marker testing is necessary. Nevertheless,
      Total Quality Management principles must be incorporated into the management of
      point-of-care testing (POCT); in this setting we implemented the Stratus CS assay
      as POCT for cardiac markers in our emergency/cardiology department. The
      analytical performance of the troponin I method was evaluated; information
      connectivity between the Stratus CS data management system and the laboratory
      information system was implemented and practical training of testing personnel
      was carried out at the POCT site. A total of 41 non-ST-segment elevation patients
      admitted to the hospital were followed to evaluate the appropriateness of
      hospital admission, formulated on the basis of the cardiac troponin-I level
      measured at the POCT site by clinical staff. Our preliminary clinical data
      suggest that the high sensitivity of the Stratus CS troponin method could play an
      important role in the early identification of patients with acute myocardial
      infarction in a low to intermediate-risk population for acute coronary syndrome.
      Our POCT model suggests that the central laboratory could ensure that the POCT
      program remains in compliance with quality requirements. Nevertheless, our
      comparison studies suggest that the implementation of POCT requires a high level
      of integration between cardiologists and pathologists to guarantee appropriate
      interpretation of the monitoring results for suspected ACS patients.

PMID- 15843219
TI  - Controlled storage conditions prolong stability of biochemical components in
      whole blood.
AB  - Blood specimens from primary care centres are normally transported to central
      laboratories by mail. This necessitates centrifugation and separation, especially
      since the potassium ion concentration in whole blood changes during storage at
      ambient temperature. Thus, because of the growing awareness of and concern for
      pre-analytical contributions to the uncertainty of measurements, we investigated
      27 components and their stability under controlled temperature conditions from 17
      to 23 degrees C. We found that storage of whole blood can be prolonged by up to 8
      12 h for all components examined, including potassium ions, when stored at 20+/
      0.2 degrees C. We conclude that this opens the possibility for establishing a
      pick-up service, by which whole blood specimens stored at 20-21 degrees C can be
      collected at the doctor's office, making centrifugation, separation and mailing
      superfluous. In addition, the turn-around time from sample drawing to reporting
      the analytical result would be shortened. After investments in thermostatted
      boxes and logistics, the system could reduce costs for transporting blood samples
      from general practice centres to central laboratories.

PMID- 15843220
TI  - Poor knowledge and faulty thinking regarding hemolysis and potassium elevation.
AB  - A questionnaire to assess knowledge of the expected elevation in serum K
      measurement with different grades of hemolysis was administered to medical
      technologists working in biochemistry laboratories, hospital physicians and
      nurses. The questions involved different grades of hemolysis (mild, 1.0,
      moderate, 2.5 and severe, 5.0 g/L) and different final K measurements (2.9, 4.0,
      5.2 and 8.2 mmol/L). Subjects estimated the K concentration in a non-hemolyzed
      sample for each scenario. Adjustment values (difference between final hemolyzed K
      concentration and subject's response) were calculated. For the 132 respondees,
      the mean correct score was 1.7/12. Mean adjustment values were: mild, 0.43 mmol/L
      (K 2.9), 0.55 (4.0), 0.88 (5.2) and 1.53 (8.2); moderate, 0.85 (2.9), 0.92 (4.0),
      1.33 (5.2) and 2.50 (8.2); and severe, 0.93 (2.9), 1.48 (4.0), 1.96 (5.2), 2.96
      (8.2). Correct adjustments were: mild, 0.28; moderate, 0.70; and severe, 1.40
      mmol/L. Healthcare staff overestimated the effect of hemolysis on potassium
      measurement and used an incorrect proportional adjustment approach to the
      problem. Such poor knowledge and faulty thinking could lead to diagnostic delays
      or misdiagnoses. There is potential for such faulty thinking in all areas of
      laboratory medicine, and laboratories should review their educational
      responsibilities and reporting practices in light of this.

PMID- 15843221
TI  - Delayed effects of short-term transdermal application of 7-oxo
      dehydroepiandrosterone on its metabolites, some hormonal steroids and relevant
      proteohormones in healthy male volunteers.
AB  - Twenty-one healthy male volunteers aged 20-70 years were given transdermally 25
      mg of 7-oxo-dehydroepiandrosterone daily in the form of an emulgel for 8
      consecutive days. Morning blood was collected as follows: before application, and
      after the first, fourth and eighth doses (days 0, 2, 5 and 9), and then at
      different time intervals after termination of the treatment (days 16, 23, 37, 51,
      72 and 100). Cortisol, testosterone, epitestosterone, estradiol,
      dehydroepiandrosterone and its sulfate, 7alpha- and 7beta-hydroxy
      dehydroepiandrosterone, luteinizing hormone, follicle-stimulating hormone and sex
      hormone-binding globulin were measured in blood sera. In the course of treatment
      7beta-hydroxy-dehydroepiandrosterone was significantly increased; testosterone
      and gonadotropins were lowered, but only after the first dose. All other
      significant changes were observed during the period after termination of the
      application:7beta-hydroxy-dehydroepiandrosterone remained increased for 28 days,
      7alpha-hydroxy-dehydroepiandrosterone, testosterone, estradiol and sex hormone
      binding globulin were decreased as late as day 63 and 91, respectively. On the
      other hand, epitestosterone was significantly increased between days 23 and 100.
      The levels of all other parameters studied were not significantly changed. The
      study points to an immediate as well as delayed effect of the short-term
      transdermal application of 7-oxo-dehydroepiandrosterone on relevant hormonal
      parameters.

PMID- 15843222
TI  - Evaluation of a novel semi-automated HPLC procedure for whole blood cyclosporin A
      confirms equivalence to adjusted monoclonal values from Abbott TDx.
AB  - The problem in the measurement of cyclosporin (CyA) is that the widely used
      immuno-based assays suffer from interference by metabolites present in
      unpredictable excess. To resolve this, the consensus view has been to develop
      more specific and robust procedures for the measurement of CyA alone in order to
      give values similar to those obtained by HPLC. We developed an alternative
      strategy based on Abbott poly- and monoclonal assays to derive an adjusted
      monoclonal value as an equivalent measurement to HPLC. We have now evaluated a
      recently developed semi-automated HPLC procedure and used it to test the validity
      of the adjusted monoclonal value. The automated HPLC procedure with online clean
      up was optimised for the separation of CyA and internal standard CyD. The assay
      was simple to use, precise and gave good recovery of cyclosporin from whole
      blood. Comparisons with the more specific immunoassays Abbott AxSym and EMIT
      showed close agreement, whereas Abbott monoclonal values indicated up to 20%
      positive bias. In contrast, the adjusted monoclonal values gave good agreement
      with HPLC. Data obtained from HPLC linked to tandem mass spectrometry (MS)
      indicated closer agreement with Abbott monoclonal values than expected,
      suggesting some positive bias with MS. The benefit of using an adjusted
      monoclonal value is that a result equivalent to HPLC is obtained, as well as an
      indication of the concentration of metabolites from the Abbott polyclonal
      measurement.

PMID- 15843223
TI  - Evaluation of the Bio-Rad VARIANT II HbA2/HbA1C Dual Program for measurement of
      hemoglobin concentrations and detection of variants.
AB  - In this work data obtained on the VARIANT II hemoglobin analyzer using the Dual
      Kit elution system were compared to those obtained with the beta-Thalassemia
      Short Program. Since many laboratories still use an earlier model of the
      hemoglobin analyzer, the Variant 1, these data were also compared to those
      obtained with the latter instrument. Our study is divided into two parts. The
      first is an evaluation of the precision of the VARIANT II for determining the
      levels of hemoglobin (Hb)A2 and Hb F. This was carried out for normal subjects,
      thalassemic patients and patients with HbS. The second part concerns the
      potential of this instrument in the presumptive identification of Hb variants.

PMID- 15843224
TI  - Interferences in coagulation tests--evaluation of the 570-nm method on the Dade
      Behring BCS analyser.
AB  - The Dade Behring BCS is a coagulation analyser with optical reaction detection
      (standard 405 nm). The present study was conducted to evaluate measurement at 570
      nm for analyses in interfering plasma samples. Prothrombin time (PT), activated
      partial thromboplastin time (aPTT), fibrinogen and D-dimer in normal (n=50),
      lipaemic (n=60), icteric (n=113), and haemolytic (n=58) samples were measured at
      405 and 570 nm. As they are unaffected by the optical properties of the sample,
      the mechanical STAcompact analyser (Roche Diagnostics) and an ELISA technique
      were defined as the "comparison" methods. The percentage of valid PT results
      using the 570-nm method varied from 54% (lipaemic samples) to 97% (haemolytic
      samples). Valid aPTT measurements were found in 67% (lipaemic samples) up to 93%
      (icteric samples) of samples. Fibrinogen measurement revealed valid results in
      58% (lipaemic samples) to 100% (haemolytic samples) of samples. The number of
      valid D-dimer results varied from 28% (lipaemic material) up to 100% (haemolytic
      material). Significant inter-method differences were found: aPTT in lipaemic (BCS
      405 vs. 570 nm) and icteric samples (STAcompact vs. BCS 405 and 570 nm);
      fibrinogen in lipaemic (BCS 405 vs. 570 nm), icteric (BCS 405 vs. 570 nm;
      STAcompact vs. BCS 570 nm) and haemolytic samples (STAcompact vs. BCS 405 and 570
      nm). Differences between the BCS 570-nm and the STAcompact methods were in most
      cases low and less pronounced than between the BCS 570- and 405-nm methods,
      making the BCS 570-nm method an alternative to measurement at 405 nm. Limitations
      have to be taken into account regarding lipaemic plasma.

PMID- 15843225
TI  - No evidence for involvement of the human inducible nitric oxide synthase gene in
      susceptibility to coronary artery disease.

PMID- 15843226
TI  - National survey on the use of measurement of cholinesterase activity in serum.

PMID- 15843228
TI  - Effect of stress doses of hydrocortisone on S-100B vs. interleukin-8 and
      polymorphonuclear elastase levels in human septic shock.
AB  - Stress doses of hydrocortisone are known to have immunomodulatory effects in
      patients with hyperdynamic septic shock. The prognosis correlates with the
      presence and severity of septic encephalopathy. However, neurological evaluation
      is influenced by the use of analgesia sedation during artificial ventilation. The
      objective of this study was to demonstrate the effect of stress doses of
      hydrocortisone during the initial phase of human septic shock on the serum values
      of the neurospecific protein S-100B in comparison to the inflammation markers
      interleukin (IL)-8 in serum and polymorphonuclear (PMN) elastase in plasma. A
      total of 24 consecutive patients, who met the American College of Chest
      Physicians/Society of Critical Care Medicine criteria for septic shock, were
      enrolled in this prospective, randomized, double-blind, single-center trial. The
      severity of illness at recruitment was graded using the Acute Physiology and
      Chronic Health Evaluation II and the Simplified Acute Physiology Score II scoring
      systems. Multi-organ dysfunction syndrome was described by the Sepsis-related
      Organ Failure Assessment (SOFA) score. All patients were prospectively randomized
      to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was
      started in 12 patients with a loading dose of 100 mg and followed by a continuous
      infusion of 0.18 mg/kg/h for 6 days. Median S-100B serum levels of the
      hydrocortisone group decreased from 0.32 ng/mL at study entry to 0.07 ng/mL 6
      days later without significant differences compared to the placebo group. Initial
      IL-8 serum levels were significantly higher in the hydrocortisone group up to 12
      h after study entry, and significantly decreased from 715 to 17 pg/mL at the end
      of the observation period. Median PMN elastase plasma levels were not affected by
      hydrocortisone infusion. Patients with initial S-100B serum levels > 0.50 ng/mL
      revealed significantly higher SOFA scores up to 30 h, IL-8 serum levels up to 12
      h, and PMN elastase plasma levels up to 36 h after study entry than those
      patients with < or = 0.50 ng/mL. These effects were independent of the amount of
      fluid correction for hemodilution. Starting S-100B, IL-8 and PMN elastase values
      of the hydrocortisone group were within the ranges already known in patients with
      out-of-hospital cardiac arrest or severe traumatic brain injury. Stress doses of
      hydrocortisone resulted in a significant reduction in IL-8 serum, but not in S
      100B serum and PMN elastase plasma concentrations in patients with hyperdynamic
      septic shock. For the first time, a similar extent of S-100B increase in serum of
      septic patients at the time of diagnosis was shown as reported for cardiac arrest
      or severe traumatic brain injury.

PMID- 15843229
TI  - Conjugated linoleic acid suppresses the secretion of atherogenic lipoproteins
      from human HepG2 liver cells.
AB  - Studies in healthy humans have shown that consumption of conjugated linoleic acid
      (CLA) significantly reduced very-low-density lipoprotein (VLDL) and low-density
      lipoprotein (LDL) blood concentrations. We propose that decreased concentrations
      are due to the inhibition of VLDL production and secretion [measured by
      apolipoprotein B100 (apoB100)] from the liver. To investigate the effects of a
      mixture of CLA isomers on VLDL metabolism, HepG2 liver cells were incubated for
      24 h with 50 micromol/L of the different fatty acids. Effects of CLA were
      compared to a saturated fatty acid (palmitic acid), an n-6 fatty acid (linoleic
      acid) and no treatment (control). HepG2-cell apoB100 levels were measured using
      Western blotting. ApoB100 secretion was significantly decreased in cells treated
      with CLA (44%, p<0.005) compared to control cells and those enriched with
      palmitic acid. Treatment of cells with CLA also decreased intracellular
      cholesterol levels. Collectively, these results demonstrate that CLA reduces
      apoB100 production and secretion compared to saturated and polyunsaturated fatty
      acids, possibly by limiting the availability of free cholesterol (required for
      apoB100 production). A reduction in apoB100 production in the body would decrease
      the levels of VLDL and atherogenic LDL and thus reduce the risk of developing
      cardiovascular disease.

PMID- 15843230
TI  - Determination of debrisoquine and 4-hydroxydebrisoquine by high-performance
      liquid chromatography: application to the evaluation of CYP2D6 genotype and
      debrisoquine metabolic ratio relationship.
AB  - The drug-metabolizing cytochrome P450 (CYP) enzyme CYP2D6 is involved in the
      metabolism of several clinically important drugs. So far more than 50 different
      CYP2D6 allelic variants have been described, and thus there is an increased need
      for routine high-performance liquid chromatography (HPLC) methods for the
      evaluation of the functional implication of CYP2D6 polymorphism. Debrisoquine is
      metabolized to 4-hydroxydebrisoquine by CYP2D6, and therefore it has been used
      widely to determine the hydroxylation capacity of the enzyme. The aim of the
      present study was to develop a simple, accurate HPLC method with ultraviolet
      detection for the measurement of debrisoquine and 4-hydroxydebrisoquine in urine
      for evaluation of the relationship between CYP2D6 enzyme activity and genotypes.
      For the HPLC determination, a C18 extraction column was used with a flow rate of
      0.8 mL/min and detection at 210 nm. The compounds were eluted from the column in
      less than 10 min. Coefficients of variation at all concentrations were less than
      4% for both compounds. The debrisoquine/4-hydroxydebrisoquine ratio (debrisoquine
      metabolic ratio) was determined in a panel of 16 Caucasian healthy volunteers
      with zero (poor metabolizers), one, two or more than two (ultrarapid
      metabolizers) CYP2D6 active genes. Significant correlation (p<0.05) between the
      number of CYP2D6 active genes and the hydroxylation capacity of the enzyme was
      found. The present HPLC method was simple, fast and accurate, and thus will be
      useful for the evaluation of CYP2D6 hydroxylation capacity in pharmacogenetic
      studies.

PMID- 15843231
TI  - Assessment of iodine intake in mildly iodine-deficient pregnant women by a new
      automated kinetic urinary iodine determination method.
AB  - Maternal iodine deficiency can compromise the thyroid status of the mother, fetus
      and newborn child. Therefore, it is important to assess the iodine excretion
      level of groups of pregnant women. In this study we aimed to determine iodine
      intake in pregnancy using a recently reported automated kinetic method for
      urinary iodine determination. Urinary iodine measurements of 123 pregnant women
      (18 first, 28 second and 77 third trimester) were carried out using a new
      automated kinetic assay based on the Sandell-Kolthoff reaction at 37 degrees C
      and its kinetic measurement at 340 nm in a random-access automated analyzer after
      ammonium persulfate digestion at 95 degrees C in a water bath with +/-0.1 degree
      C precision. Statistical analyses were carried out using SPSS software. Whole
      group, first trimester, second trimester and third trimester urinary iodine
      concentrations (mean+/-SD) in pregnant women were 1.13+/-0.81, 1.08+/-0.71,
      0.86+/-0.58 and 1.27+/-0.87 micromol/L, respectively. The urinary iodine
      concentration significantly increased with gestational age (p<0.05). We found
      that our study group was mildly iodine-deficient according to WHO criteria.
      Furthermore, the pregnant women were found to be mildly iodine-deficient in the
      first and third trimesters and moderately so in the second trimester. The only
      statistical difference was between second and third trimester values (p<0.05).
      Even though the increased iodine deficiency in the second trimester is not useful
      for early detection of iodine deficiency in pregnancy, the severity of this
      deficiency in the second trimester may lead to important effects on thyroid
      metabolism for both mother and fetus. Our study suggests that the iodine
      excretion of pregnant women living in iodine-deficient areas could be assessed
      using this fast and automated method.

PMID- 15843232
TI  - Butyrylcholinesterase activity and metabolic syndrome in obese patients.
AB  - Total butyrylcholinesterase activity (EC 3.1.1.8) was previously suggested as a
      marker for metabolic syndrome. The present study examined total
      butyrylcholinesterase activity and the relative and absolute activities of two
      butyrylcholinesterase electrophoretic bands (C(4/5) and C(OF) in 99 obese
      individuals (body mass index > or = 30 kg/m2) presenting the CHE2 C5- phenotype
      of the CHE2 gene. Anthropometric, hormonal and biochemical variables already
      associated with metabolic syndrome were also examined. The data from these obese
      individuals of the CHE2 C5- phenotype show that total butyrylcholinesterase
      activity and the absolute activities of the C(4/5) and C(OF) electrophoretic
      bands are associated with metabolic syndrome and with variables related to it.
      These butyrylcholinesterase activities do not behave as independent risk factors
      for metabolic syndrome, but can be considered as secondary markers for this
      syndrome in obese individuals with the CHE2 C5- phenotype.

PMID- 15843233
TI  - The non-thyroidal illness syndrome after coronary artery bypass grafting: a 6
      month follow-up study.
AB  - The non-thyroidal illness syndrome (NTIS) is considered a transient and
      completely reversible phenomenon, but it has been shown that it may last for
      several days postoperatively after coronary artery bypass grafting (CABG)
      surgery. This study was undertaken to assess thyroid function 6 months after
      uncomplicated CABG. The thyroid profile was evaluated in 40 consecutive patients
      undergoing CABG preoperatively, at 0, 12, 48, and 120 h postoperatively, and at 6
      month follow-up. Triiodothyronine (T3), free T3 (FT3), free thyroxine (FT4) and
      thyroid stimulating hormone (TSH) were assayed using a microparticle enzyme
      immunoassay. T4 and total serum thyroid hormone-binding capacity (T-uptake) were
      measured on the same samples using a fluorescence polarization immunoassay.
      Patients with severe systemic illness and patients treated with amiodarone were
      excluded. All patients were euthyroid at admission. Mean age was 67.4+/-9.0
      years. There were 31 (77.5%) men. Typical NTIS was observed in all patients, and
      the FT3 concentration was still reduced by postoperative day 5 (p<0.0001). At 6
      month follow-up, all patients were free from cardiac symptoms, and no new cardiac
      events were recorded. The thyroid profile was normal in 35 patients (87.5%). One
      patient (4.5%) had developed overt hypothyroidism. Two patients had isolated low
      T3 and FT3 levels with normal TSH. Two patients had moderately increased FT3
      levels with suppressed TSH. In most uncomplicated patients, thyroid function
      returns to normal 6 months after CABG. However, we observed significant
      alterations of the thyroid profile in 5 out of 40 patients. Further studies are
      needed to define the long-term consequences of postoperative NTIS.

PMID- 15843234
TI  - Advanced oxidation protein products (AOPP) for monitoring oxidative stress in
      critically ill patients: a simple, fast and inexpensive automated technique.
AB  - Oxidative stress is known to be involved in many human pathological processes.
      Although there are numerous methods available for the assessment of oxidative
      stress, most of them are still not easily applicable in a routine clinical
      laboratory due to the complex methodology and/or lack of automation. In research
      into human oxidative stress, the simplification and automation of techniques
      represent a key issue from a laboratory point of view at present. In 1996 a novel
      oxidative stress biomarker, referred to as advanced oxidation protein products
      (AOPP), was detected in the plasma of chronic uremic patients. Here we describe
      in detail an automated version of the originally published microplate-based
      technique that we adapted for a Cobas Mira Plus clinical chemistry analyzer. AOPP
      reference values were measured in plasma samples from 266 apparently healthy
      volunteers (university students; 81 male and 185 female subjects) with a mean age
      of 21.3 years (range 18-33). Over a period of 18 months we determined AOPP
      concentrations in more than 300 patients in our department. Our experiences
      appear to demonstrate that this technique is especially suitable for monitoring
      oxidative stress in critically ill patients (sepsis, reperfusion injury, heart
      failure) even at daily intervals, since AOPP exhibited rapid responses in both
      directions. We believe that the well-established relationship between AOPP
      response and induced damage makes this simple, fast and inexpensive automated
      technique applicable in daily routine laboratory practice for assessing and
      monitoring oxidative stress in critically ill or other patients.

PMID- 15843235
TI  - Quality control in urinary stone analysis: results of 44 ring trials (1980-2001).
AB  - Urinary stone analysis is the most important diagnostic step after stone removal
      from the body. The methods employed for these analyses are based on diverse
      analytical principles. Chemical methods are used for detecting individual ions.
      Infrared spectroscopy is used for examining molecular structures, and X-ray
      diffraction for determination of the crystalline structure of a substance. Since
      1980, a twice-yearly ring trials quality control survey has been on offer to
      examine the quality of urinary stone analyses. A summary of the results of 44
      ring trials (1980-2001) has been compiled for individual pure substances and
      binary (two-component) mixtures. On average, 100 laboratories have participated
      in these ring trials. Initially, over 80% of the participants carried out their
      analyses using chemical methods. In 2001, this figure decreased to a mere 13%. In
      contrast, a progressive increase in the use of infrared spectroscopy was
      observed, up to 79% of all participants employed this method. X-Ray diffraction
      was only employed in a small number of specialised laboratories (5-9%). The
      chemical methods produced a very high proportion of errors (6.5-94%) with both
      the pure substances and binary mixtures, whereas high error rates for infrared
      spectroscopy and X-ray diffraction were confined to individual substances only.
      Due to the poor results in the ring trials, the majority of laboratories stopped
      using chemical analysis, which is now considered to be obsolete. Regarding
      mixtures, error rates of over 10% also occurred with infrared spectroscopy and X
      ray diffraction. Ring trials are indispensable for the quality management of
      urinary stone analysis.

PMID- 15843236
TI  - External Quality Assessment in The Netherlands: time to introduce commutable
      survey specimens. Lessons from the Dutch "Calibration 2000" project.
AB  - The performance of suitable secondary reference material for the use of trueness
      control of six routinely measured clinical enzymes in the Dutch External Quality
      Assessment (EQA) scheme is described. The reference material of choice was
      selected using the split-patient-sample between-field method (twin study) design
      as described in an earlier study of the Calibration 2000 project in The
      Netherlands. This material, which was proven to be commutable for all wet
      chemistry systems, was implemented as the national enzyme calibrator. It
      consisted of a cryo-protected lyophilised serum with additions of recombinant
      human enzymes. Various batches of the frozen version of this material without
      cryo-protection additive, called native EQA samples, were used in the general EQA
      scheme for performance evaluation. The results of Calibration 2000 calibrated and
      non-Calibration 2000 calibrated laboratories were compared for both the regular
      (spiked with non-human enzymes) and native EQA samples in terms of precision and
      bias with established reference method values for the native samples. The regular
      samples showed mean between-laboratory CV ranges for all six enzymes involved
      (low-high) of 5.5-10.3% for the non-calibrated users vs. 4.6-10.8% for the
      calibrated users. For the native samples these respective ranges were 5.2-9.9%
      vs. 2.2-4.9%. Without exception, the group of Calibration 2000 calibrated users
      showed the lowest bias against the reference method values. Regular EQA samples
      (spiked with non-human enzymes) showed poorer performance than native samples and
      are not suitable for accuracy assessment purposes, the main aim of EQA schemes.
      Native samples that are commutable should be used for trueness control in current
      EQA schemes.

PMID- 15843237
TI  - Evaluation of a high-sensitivity turbidimetric immunoassay for serum C-reactive
      protein: application to the study of longitudinal changes throughout normal
      pregnancy.
AB  - C-Reactive protein has been associated with several complications of pregnancy.
      The aims of the present study were: (1) to evaluate a turbidimetric immunoassay
      for the measurement of C-reactive protein; and (2) to investigate the
      chronological changes of the levels of this protein from preconception throughout
      normal pregnancy and its relationship with variables associated with
      preconception and pregnancy outcome. Inter-assay imprecision was <5% for C
      reactive protein >1 mg/L and 18% at a mean value of 0.33 mg/L. The limit of
      detection was 0.10 mg/L. The method was linear between 0.10 and 30 mg/L. There
      were no observed interferences from jaundice, hemolysis, lipemia or
      paraproteinemia at the levels studied. There was good agreement with the
      nephelometric method. A total of 39 women were studied at preconception, at 8, 20
      and 32 weeks of pregnancy, and in labor. Preconception C-reactive protein
      concentration was 1.17+/-0.18 mg/L and increased (p<0.001) throughout pregnancy
      up to 5.69+/-0.82 mg/L. Body mass index at preconception and weight gain during
      pregnancy were the main factors associated with this increase in C-reactive
      protein.

PMID- 15843238
TI  - A quantitative appraisal of interference by icodextrin metabolites in point-of
      care glucose analyses.
AB  - An important number of patients dependent on renal dialysis prefer peritoneal
      dialysis to hemodialysis. In the case of peritoneal dialysis, the glucose polymer
      icodextrin is frequently added to the dialysis fluid as an osmotic agent, since
      this polymer is able to maintain an osmotic gradient across the peritoneal
      membrane longer than monomeric glucose, leading to a prolonged effective
      ultrafiltration time. It was previously shown that icodextrin is partly able to
      enter the blood via the lymphatic system, where hydrolysis to glucose oligomers
      such as maltose and maltotriose occurs. The presence of these oligomers in the
      blood appears to cause significant overestimations of the glucose values in
      several point-of-care (POC) glucose analyzers, with potentially dramatic
      consequences. This effect has been investigated for a series of POC glucose
      analyzers, both by analyzing the blood of peritoneal dialysis patients and by an
      in vitro investigation of the quantitative effects of maltose and maltotriose. In
      particular, POC analyzers utilizing the bacterially produced enzyme glucose
      dehydrogenase seem to lack glucose specificity.

PMID- 15843239
TI  - Preanalytical variability in laboratory testing: influence of the blood drawing
      technique.
AB  - The predominant technique used to draw blood for laboratory testing is a
      conventional straight needle attached to an evacuated tube system. However,
      alternative tools might be advantageous in exceptional circumstances. The use of
      butterfly devices has been traditionally discouraged for reasons of costs and due
      to the high risk of obtaining unsuitable samples, but there is no convincing
      evidence to support the latter indication. The purpose of this study was to
      compare results of hematological and clinical chemistry testing, after drawing
      blood into evacuated tubes, employing either a traditional 21-gauge straight
      needle or a 21-gauge butterfly device with 300-mm-grade polyvinyl chloride
      tubing. Blood samples and complete sets of data were successfully obtained for 30
      consecutive outpatients. Of the 43 hematological and clinical chemistry
      parameters measured, means for paired samples collected by the two alternative
      drawing techniques did not differ significantly, except for serum sodium, white
      blood cells and platelets counts. Bland-Altman plots and limits-of-agreement
      analysis showed mean bias of between -7.2% and 1.7% and relative coefficients of
      variation ranging from 0.2% to 21.2%. The 95% agreement interval in the set of
      differences was acceptable and was mostly within the current analytical quality
      specifications for desirable bias. The rate of hemolysis in plasma was not
      statistically different between the two collection techniques. Taken together,
      the results of the present investigation suggest that, when a proper technique is
      used and within certain limitations, the butterfly device may be a reliable
      alternative to the conventional straight needle to draw blood for laboratory
      testing.

PMID- 15843240
TI  - Soluble transferrin receptor and transferrin receptor-ferritin index in iron
      deficiency anemia and anemia in rheumatoid arthritis.
AB  - The aim of the study was to evaluate the clinical efficiency of soluble
      transferrin receptor and transferrin receptor-ferritin index (sTfR/logF) in the
      diagnosis of iron deficiency anemia, as well as the differential diagnosis of
      iron deficiency anemia and anemia in rheumatoid arthritis. The study included 96
      patients with anemia and 61 healthy volunteers as a control group. In healthy
      subjects there were no significant sex and age differences in the parameters
      tested. The study results showed these parameters to be reliable in the diagnosis
      of iron deficiency anemia, as well as in the differential diagnosis of iron
      deficiency anemia and anemia of chronic disease. The results indicate that
      sTfR/logF could be used to help differentiate coexisting iron deficiency in
      patients with anemia of chronic disease. Receiver operating characteristic
      analysis showed a higher discriminating power of transferrin receptor-ferritin
      index vs. soluble transferrin receptor in the diagnosis of iron deficiency
      anemia, as well as in the differential diagnosis between iron deficiency anemia
      and anemia of chronic disease. In patients with anemia in rheumatoid arthritis,
      the parameters tested showed no significant differences with respect to C
      reactive protein concentration. These results suggested that the parameters
      tested are not affected by acute or chronic inflammatory disease.

PMID- 15843241
TI  - Elevated plasma cysteinylglycine levels caused by cilastatin-associated
      antibiotic treatment.
AB  - Imipenem (thienamycin formamidine), a broad-spectrum beta-lactam antibiotic, is
      always used in combination with cilastatin in order to avoid the premature
      breakdown of imipenem by renal tubular dipeptidase. As this dipeptidase also
      hydrolyzes the glutathione metabolite cysteinylglycine, the therapeutic
      association of imipenem and cilastatin might cause an accumulation of the
      aminothiol cysteinylglycine. We demonstrate here that when patients are treated
      with imipenem-cilastatin, their plasma levels of cysteinylglycine are
      significantly and specifically increased, while cysteine levels are decreased and
      homocysteine levels are unaffected. We conclude that antibiotic treatment using
      imipenem-cilastatin induces important metabolic changes that should not remain
      unrecognized.

PMID- 15843242
TI  - The number of consultant clinical chemists in the 15-nation European Union.
AB  - The number of consultant clinical chemists (NCCC) in the 15-nation European Union
      (EU) (Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland,
      Italy, Luxembourg, The Netherlands, Portugal, Spain, Sweden, United Kingdom) has
      been ascertained. These data were analysed in relation to several established
      national parameters, including demographics, gross domestic product (GDP), cost
      of healthcare, cost of in vitro diagnostic (IVD) testing and the number of
      physicians and pharmacists. Large differences in the population-corrected costs
      of IVD testing (range approximately 2.4-fold) and NCCC (range approximately 30
      fold) were observed between the countries, which could not be satisfactorily
      explained by any of the parameters assessed. The differences in IVD testing and
      NCCC might reflect different practices in laboratory medicine across the EU, but
      could not be estimated independently. In recognition of the different scope of
      laboratory medicine practised under the title of clinical chemistry, a simple
      staffing model was derived in an attempt to give a better estimate of the
      appropriate number of consultant laboratory medicine specialists. This model
      allocated a fixed number of laboratory specialists per million inhabitants for
      the five disciplines: clinical chemistry, 10; haematology, 10; serology, 7.5;
      microbiology, 12.5; and blood banking, 2. The staffing model also allowed for the
      contribution of the primary care sector by including one full-time consultant
      laboratory medicine specialist for each small private laboratory and two extra
      consultant laboratory specialists per million inhabitants where there are not
      large numbers of private laboratories. Application of the model to the available
      data helped to reduce the variation observed in the primary analysis of NCCC
      (range approximately 9-fold) but still revealed important differences between
      countries. These differences could arise from the poor quality of published data
      as much as from true differences in laboratory medicine practice. We conclude
      that a more sophisticated analysis of laboratory practice and of all
      professionals working in laboratory medicine disciplines would be required before
      any conclusions could be drawn about relative staffing, efficiency or cost
      effectiveness. The staffing model derived is a first step towards objective
      estimation of the number of consultant laboratory specialists in the EU.

PMID- 15843243
TI  - Biological variation of vascular endothelial growth factor.

PMID- 15843244
TI  - Terminology, categories and representation of examinations in laboratory
      medicine.

PMID- 15843245
TI  - Reply to W.G. Wood. Questionable results--who directs the EQAS organisers? Clin
      Chem Lab Med 2004;42:1073.

PMID- 15843246
TI  - Introduction.
AB  - In this introduction to the special issue on "Group Therapist Countertransference
      to Trauma and Traumatogenic Situations," the author notes that for many
      therapists it is not only group member disclosures and re-enactments, but also
      the co-occurring, sociopolitical contexts in which they live that may involve
      traumatic challenges. He considers three historically evolving views of
      countertransference: (1) the "classical" position, (2) the "totalistic" view, and
      (3) the "intersubjective/relational" view. He views the therapist's intense
      emotionality (as opposed to clinical detachment) in response to trauma as
      inevitable, and considers the particular roles of "bystander," "perpetrator," and
      "victim" induced in the therapist by traumatic re-enactments in the group. He
      concludes with a synopsis of some of the key points made in each of the
      contributions to the special issue.

PMID- 15843247
TI  - In the Belly of the Beast: Traumatic Countertransference.
AB  - The authors discuss their work together in a consultation process. One author led
      many groups that were created to facilitate recovery for persons directly
      impacted by the terrorist attacks on September 11, 2001; the other acted as
      consultant to the therapist/leader. The leader was a resident of New York City at
      the time of the attacks; the consultant lived in a distant Midwestern city and
      the two had never met prior to the work. They describe their experience of
      working together and the role of this collaboration in the lives of the leader
      and the groups. Well aware that little exists in the literature about groups led
      by leaders having experienced the same trauma as group members, the authors pay
      special attention to the countertransference that each underwent and raise
      questions about the effects of that on the group process.

PMID- 15843248
TI  - The Effect of Trauma on the Conductor of the Group: A Type of Identificatory
      Countertransference.
AB  - Trauma affects the conductor of the group as well as the group members. This
      identificatory countertransference of the group conductor is a resultant of the
      coming together of the conductor's internal and external worlds, the interplay of
      introjections, projections, and empathy. It is inconceivable that a conductor of
      a group can project a "blank screen" of technical neutrality when trauma impinges
      upon everyone. From a psychodynamic perspective, this article explores groups
      under the throes of trauma, the interplay of that trauma with the conductor's
      feelings, and the effects on his or her role in the group. The article also
      explores the effect of trauma upon the affective process within the group and
      upon the cognitive processes of the conductor and group members.

PMID- 15843249
TI  - Management of Intense Countertransference in Group Psychotherapy Conducted in
      Situations of Civic Conflict.
AB  - Conducting group psychotherapy in a situation of intractable conflict such as
      Northern Ireland activates turbulent emotional dilemmas within psychotherapists
      and group members alike. Professional practice and therapeutic zeal must struggle
      daily to survive the stark encounter with the reality of a regressive and
      primitive psychology and on occasion may succumb to atavistic tendencies,
      dragging relationships down to primitive levels and leaving connections broken.
      In this article, three group therapists describe their countertransference
      struggles when leading such groups. They meet in a psychosocial setting in which
      the risk to one's psyche parallels the risk to one's life and limb. The
      countertransference experienced here is dark, indeed identified by one author as
      not unlike Dante's Inferno. They describe how understanding their personal
      countertransference enables them to survive emotionally even though it may not
      always lead to the survival of their groups. The effect of those struggles also
      troubled the act of writing itself, making cooperation difficult on occasion, a
      mirror of the external social matrix.

PMID- 15843250
TI  - Countertransference in the Context of the Fourth Basic Assumption in the
      Unconscious Life of Groups.
AB  - The treatment of choice for traumatized and difficult patients is psychoanalysis
      or psychoanalytical therapy followed by intensive group analysis for an unlimited
      period of time. The group is able to help the analyst make therapeutic use of
      inevitable difficulties in countertransference processes. Also, traumatized and
      difficult patients are likely to create the basic assumption of Incohesion:
      Aggregation/Massification, and to personify the roles associated with it. These
      processes can be used in order to provide such patients with appropriate
      therapeutic attention involving both containment and holding, and interpretation.
      Extensive clinical data from psychoanalysis and group analysis are used to
      illustrate both this clinical approach and the author's theory of Incohesion.

PMID- 15843251
TI  - Relational Perspectives Regarding Countertransference in Group and Trauma.
AB  - A relational/constructivist view incorporates contemporary trends toward viewing
      countertransference and co-transference as results of mutual intersubjective
      influence. It moves toward a view of the socially constructed nature of human
      reality, toward recognizing the therapist's as well as the members' irreducible
      individuality and initiative taking, and toward therapy as about meaning-making
      rather than scientific discovery of The Truth. General clinical examples, and
      examples of working specifically with trauma, are given.

PMID- 15843252
TI  - Holding Hope and Humanity in the Face of Trauma's Legacy: The Daunting Challenge
      for Group Therapists.

PMID- 15843253
TI  - Countertransference: The Evolution of a Construct.

PMID- 15843254
TI  - Group Therapy for Patients with Chronic Trauma-Related Stress Disorders.

PMID- 15843255
TI  - Declining fertility in the developed world and high maternal mortality in
      developing countries--how do we respond?

PMID- 15843256
TI  - Maternal obesity and complications during pregnancy.
AB  - Obesity has become a major health problem all over the world and during pregnancy
      is associated with an increased risk of complications, including gestational
      diabetes, preeclampsia, and delivery complications such as macrosomia, shoulder
      dystocia and higher rates of cesarean sections and infections. Maternal obesity
      may also be an independent risk factor for neural tube defects and fetal
      mortality. This review focuses on the consequences of maternal obesity during
      pregnancy.

PMID- 15843257
TI  - Cesarean section upon request: is it appropriate for everybody?
AB  - The request for cesarean section without medical indication has become one of the
      dilemmas faced by the obstetrician. Most recent studies that compare vaginal
      delivery with elective cesarean section find them equally safe. This comparison
      is lacking in the option of trial of labor, which may result in an assisted
      vaginal delivery or intrapartum cesarean section, both with increased morbidity
      and mortality for the mother and newborn. When considering elective cesarean
      section, the obstetrician has to take into account improved anesthetic techniques
      and the decrease in morbidity and mortality after cesarean section with the trend
      toward patient autonomy to decide on her own treatment. On the other hand, the
      obstetrician has to advise his patient of the best treatment with respect to
      possible complications in future pregnancies, such as placental complications and
      increased morbidity and mortality resulting from repeated cesarean sections. The
      advantage of cesarean section for pelvic floor protection does not exist after
      three consecutive cesarean sections and equals the rate of urinary incontinence
      after consecutive three vaginal deliveries. In countries such as ours, where most
      women wish for several children, the risk-benefit balance is toward repeated
      spontaneous vaginal deliveries.

PMID- 15843258
TI  - Reply to: Cesarean section upon request: is it appropriate for everybody?

PMID- 15843259
TI  - Characteristics of mothers who delivered the heaviest, average-weight, and
      lightest triplet sets.
AB  - We analyzed a cohort of 2850 live-born triplet sets to compare age, parity,
      stature, pre-gravid body mass index (BMI), and weekly weight gain in mothers who
      delivered triplets with a total weight in the 10th, 5th, and 1st deciles
      corresponding to the heaviest, average-weight, and lightest triplet sets,
      respectively. Mothers who delivered the heaviest triplets were significantly
      older, multiparous, taller, heavily built, and gained more weight compared with
      mothers of average-weight triplets. In contrast, except for higher parity,
      mothers of average-weight sets were not significantly different compared with
      mothers who delivered the lightest triplet sets. We concluded that parity was the
      only significant factor for increased total triplet weight in the first five
      deciles. However, the presence of other factors in addition to parity is needed
      for a triplet pregnancy to be included in the 10th decile.

PMID- 15843260
TI  - Gestational age-specific distribution of twin birth weight discordance.
AB  - AIM: To examine the gestational age-specific distribution of twin birth weight
      discordance. METHODS: We analyzed all liveborn twin sets between 28 and 40 weeks'
      gestation from the United States 1995-1998 Multiple Matched Birth Data Set
      compiled by the National Center for Health Statistics. We calculated the 50th and
      95th percentiles of birth weight discordance at each gestational age. Neonatal
      mortality rates were calculated for discordant twins at the 95th percentile of
      birth weight discordance for each gestational age. RESULTS: At older gestational
      ages, the 95th percentile of birth weight discordance resulted in an inter-twin
      birth weight difference of approximately 25%, a value often used to define twins
      as birth weight discordant. However, at earlier gestational ages, the 95th
      percentile of birth weight discordance was greater, reaching nearly 50% at 28
      weeks. CONCLUSIONS: The inter-twin birth weight difference at the 95th percentile
      is greater at lower gestational ages, possibly illustrating the different nature
      or severity of twin birth weight discordance at an earlier gestational age.

PMID- 15843261
TI  - The comparison of amino-terminal probrain natriuretic peptide levels in
      preeclampsia and normotensive pregnancy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the levels of amino-terminal
      probrain natriuretic peptide (Nt pro-BNP) in preeclampsia in comparison with
      normotensive pregnancy. MATERIALS AND METHODS: Women with preeclampsia
      (proteinuria > or = 300 mg/24 h and at least two readings of systolic blood
      pressure > or = 140 mm Hg and diastolic blood pressure > or = 90 mm Hg) (n = 32
      mild preeclampsia and n = 8 severe preeclampsia) were compared with normotensive
      women (n = 40). Serum Nt pro-BNP was measured using an electrochemiluminescence
      immunoassay (ECLIA) method (Nt pro-BNP, Roche) with a Roche modular analytics
      E170 immunoassay analyzer. Statistical analysis was carried out by the Student t
      test, and a P value of <0.05 was accepted as statistically significant. RESULTS:
      The median serum Nt pro-BNP was 430+/-28.91 pg/mL in preeclampsia. The levels of
      serum Nt pro-BNP were 74+/-16.82 pg/mL in normotensive pregnant women (P < 0.001)
      and significantly higher in women with preeclampsia (P < 0.001). CONCLUSION: The
      higher levels of serum Nt pro-BNP in preeclamptic women may be an indicator of
      high left-ventricular filling pressure, and indicate left-ventricular diastolic
      dysfunction.

PMID- 15843262
TI  - Optimal timing for postprandial glucose measurement in pregnant women with
      diabetes and a non-diabetic pregnant population evaluated by the Continuous
      Glucose Monitoring System (CGMS).
AB  - OBJECTIVE: Using the Continuous Glucose Monitoring System (CGMS; Medtronic
      Minimed) for a group of pregnant women with and without glucose intolerance, we
      attempted to answer the following questions: (1) when does the physiological peak
      of postprandial glucose occur?; (2) do non-diabetic pregnant women and pregnant
      women with diabetes have different postprandial glucose profiles?; and (3) what
      is the optimal time for postprandial glucose measurement rated according to
      clinical outcome? METHODS: We included 53 pregnant women in our study. Based on
      the criteria of the German Diabetes Association (fasting, 5.0 mmol/L; 1-h, 10.0
      mmol/L; 2-h, 8.6 mmol/L) we included 13 women with gestational diabetes, four
      with type 1 diabetes and 36 non-diabetic pregnant (NDP) women. Gestational and
      type 1 diabetics were classed as one group: pregnancy complicated by diabetes
      (PCD). Patients with carbohydrate intolerance underwent dietary counseling in
      accordance with the recommendations of the American Diabetes Association.
      Patients received a CGMS for use over 72 h. This was calibrated seven times a day
      with an Accu-Check. The pre- and postprandial glucose levels were documented at
      15-min intervals for 3 h from the beginning of each meal. The postprandial data
      from the three meals were added. The group was divided according to three
      clinical outcome parameters: mode of delivery, birth weight percentile, and
      diabetes-associated complications. RESULTS: Statistically significant differences
      between groups were found for body mass index, fetal birth weight and oral
      glucose tolerance test. No significant differences were found for age, parity and
      gestational age, mode of delivery, and diabetes-associated complications. The
      sensor provided similar numbers of measurements in both groups (278+/-43 vs.
      298+/-73, P = 0.507). The postprandial glucose peak was reached after 82+/-18 min
      in the non-diabetics vs. 74+/-23 min in the PCD group (not significant).
      Postprandial glucose values were normally slightly higher in PCD (not
      significant). We added the postprandial glucose values at each time interval for
      the three meals for each day. For the sum, there was a significant difference
      between the measurements at 120 min and at 135 min postprandial (P < 0.05).
      Dividing the group by clinical outcome showed a significant difference between
      the postprandial time intervals of 75 min and 105 min (P < 0.05). In addition,
      the time interval was different from 60 min to 135 min for the mode of delivery
      and birth weight percentile (P < 0.05). CONCLUSION: The 120-min interval is too
      long and has a lower correlation to clinical outcome parameters than earlier
      measurements. Our findings show that the optimal time for testing is between 45
      and 120 min postprandial. Based on our practical experience and dietary
      recommendations, we would prefer a 60-min interval, because patients can
      calculate this more easily and can have more freedom to eat the recommended
      number of snacks.

PMID- 15843263
TI  - Structural-tridimensional study of yolk sac in pregnancies complicated by
      diabetes.
AB  - OBJECTIVES: To assess by two- and three-dimensional ultrasound the diameter and
      volume of the yolk sac in pregnant women affected by type 1 diabetes during the
      first trimester of pregnancy. METHODS: 18 women affected by insulin-dependent
      diabetes mellitus (IDDM) and 52 normoglycemic pregnant women (controls) were
      enrolled in this study. The women were evaluated once a week (5-12 weeks of
      pregnancy). Ultrasound examination in all pregnant women was initially performed
      in a bidimensional fashion with a transvaginal 6.5-MHz probe and subsequently
      using a three-dimensional technique. RESULTS: In the pregnant diabetic women the
      diameter of the yolk sac was significantly higher than that of controls in the
      first weeks of pregnancy, reaching a maximum diameter at 9 weeks, and decreasing
      thereafter, earlier than controls. The volume of the yolk sac increased in both
      groups from 5 weeks of pregnancy and reached maximum values at 10 weeks in both
      groups. The volumetric increase and decrease after reaching highest values were
      greater in IDDM patients. CONCLUSION: The clinical and diagnostic implications of
      the results of this study are still to be defined. Such a diagnostic technique
      may prove to be an additional element in monitoring diabetic women during early
      pregnancy.

PMID- 15843264
TI  - Is cervical dilatation during parturition at term associated with apoptosis?
AB  - AIMS: Cellular turnover may be involved in remodeling of the cervix during
      parturition. Therefore, the number and localization of apoptotic and
      proliferating cells during cervical dilatation at term were determined. METHODS:
      Biopsy specimens from the lower uterine segment of 36 women undergoing cesarean
      section with a cervical dilatation of < 2 cm (n = 10), 2- < 4 cm (n = 9), 4-6 cm
      (n = 8), and > 6 cm (n = 9) were examined for nuclear fragmentation by the TUNEL
      assay, and for cell survival by the apoptosis-blocking bcl-2. Proliferation was
      marked by Ki-67, epithelial cells by cytokeratin and leukocytes by CD 45. For
      quantification of apoptotic and proliferating cells, eight random fields of each
      specimen stained for TUNEL or Ki-67 were blindly counted by two investigators.
      For statistical evaluation, 90% confidence intervals based on a Poisson
      distribution were used; groups with non-overlapping intervals were considered
      significantly different. RESULTS: Apoptotic cells were found exclusively within
      the stromal compartment, while bcl-2 was expressed in epithelial cells and
      leukocytes. Proliferating cells were of stromal and epithelial origin. The number
      of apoptotic as well as proliferating cells ranged from 0 to 2 cells per high
      power field (median number 0) in all groups. The confidence intervals were
      overlapping for all groups, showing no statistical difference between them.
      CONCLUSION: Apoptosis does not seem to play a decisive role in the process of
      cervical dilatation during parturition at term.

PMID- 15843265
TI  - Increased soluble VCAM-1 serum levels in preeclampsia are not correlated to
      urinary excretion or circadian blood pressure rhythm.
AB  - OBJECTIVE: Soluble vascular cell adhesion molecule-1 (VCAM-1) is known to be
      elevated in serum of patients with preeclampsia, but there are no data available
      on the significance of urinary VCAM-1 excretion in preeclampsia. The aim of our
      study was to uncover possible circadian rhythms of VCAM-1 plasma levels and
      urinary VCAM-1 excretion in uncomplicated and hypertensive pregnancies and to
      ascertain their relation to blood pressure. STUDY DESIGN: A total of 10
      normotensive and 10 preeclamptic pregnant women were included in this study.
      Venous blood was collected hourly, and urine samples were taken every 2 h over a
      period of 24 h. VCAM-1 levels were determined by ELISA. We compared these results
      with the circadian blood pressure rhythm. RESULTS: The median VCAM-1 plasma
      levels were significantly (P < 0.01) increased in preeclamptic patients (851.5
      ng/mL) in comparison to normotensive pregnant women (659.3 ng/mL) without any
      circadian rhythm being apparent; however, the urinary excretion of VCAM-1 showed
      a typical circadian rhythm, with a higher excretion rate during daytime.
      CONCLUSION: For the first time we have demonstrated that urinary VCAM-1 excretion
      in pregnancy shows a circadian rhythm without correlation to plasma levels or the
      circadian blood pressure rhythm. In contrast, VCAM-1 serum levels did not show a
      diurnal rhythm. We assume that VCAM-1 serum levels do not correlate with systemic
      blood pressure or urinary excretion.

PMID- 15843266
TI  - The association of birthweight with maternal and cord serum and amniotic fluid
      growth hormone and insulin levels, and with neonatal and maternal factors in
      pregnant women who delivered at term.
AB  - AIM: To investigate the influence of maternal and cord serum and amniotic fluid
      growth hormone (GH) and insulin and other neonatal and maternal factors on
      birthweight. METHODS: A total of 160 pregnant women at 38-42 weeks' gestation
      were studied. All infants were categorized as small for gestational age (SGA) (n
      = 50), large for gestational age (LGA) (n = 50) or average for gestational age
      (AGA) (n = 60). GH and insulin levels were measured in maternal and cord serum
      and amniotic fluid at birth. RESULTS: GH levels in maternal and cord serum and
      amniotic fluid showed no differences among the three weight groups (P > 0.05).
      The cord insulin level was significantly lower in SGA (P < 0.01). The insulin
      level in venous cord blood correlated with birth and placental weights and
      neonatal height, whereas maternal serum and amniotic fluid insulin levels, and
      maternal and cord serum and amniotic fluid GH levels did not show any correlation
      with birthweight. The cord GH level at birth was correlated with GH levels after
      4 postnatal weeks in the SGA group (P < 0.01). In addition, birthweight showed a
      correlation with prepartum maternal weight, maternal weight gain, maternal
      height, neonatal length and placental weight in all three weight groups.
      CONCLUSIONS: Cord GH, maternal serum and amniotic fluid GH and insulin levels did
      not correlate with birthweight in all three weight groups. The lack of
      correlation for GH levels in maternal and cord serum and amniotic fluid suggests
      that these compartments may be non-communicating separate units.

PMID- 15843267
TI  - Amniotic fluid lamellar body counts for the determination of fetal lung maturity:
      an update.
AB  - AIM: To reassess the cut-off value for lamellar body counts (LBs) for fetal lung
      maturity (FLM) over a 10-year study period. PATIENTS AND METHODS: 178 pregnancies
      were selected under strict inclusion criteria and delivered within 48 h from
      amniocentesis. FLM was determined by amniotic fluid LBs in centrifuged samples
      (300 x g for 10 min) in a commercially available Coulter Counter. Cases beyond 37
      weeks were excluded. RESULTS: Mean gestational age was 33.5+/-3.0 weeks at
      amniocentesis and 33.7+/-3.0 weeks at birth. After reassessing the best
      compromise between sensitivity and specificity for all cases using the receiver
      operating characteristic (ROC) procedure, an FLM cut-off value of < or =
      22,000/microL was obtained. Diagnostic accuracy (and confidence interval, CI)
      was: sensitivity, 73% (60.0-83.6%); specificity, 81.7% (CI 73.6-88.1%); positive
      predictive value, 66.2%; and negative predictive value, 86.0%. CONCLUSION: No
      significant change in FLM cut-off for LBs was found when comparing the value from
      this study and the results of our earlier report presented in 1996 (< or = 22,000
      vs. < or = 20,000/microL), although the new value may be more accurate, since it
      is based on neonatal outcome with the exclusion of cases in which the diagnosis
      of FLM is seldom warranted, i.e., > 37 weeks' gestational age.

PMID- 15843268
TI  - Comparison of clinical criteria with echocardiographic findings in diagnosing PDA
      in preterm infants.
AB  - OBJECTIVE: The purpose of our study was to compare clinical criteria with
      echocardiographic findings in diagnosing hemodynamically significant patent
      ductus arteriosus (PDA) in preterm infants. METHODS: We evaluated 25 preterm
      infants born at 24-32 weeks of gestation with birth weight from 500 to 1700 g for
      tachycardia, heart murmur, hyperdynamic chest, presence of dorsalis pedis pulse,
      hypotension, and worsening of the respiratory status at 48-72 h of life. A
      pediatric cardiologist blinded to clinical findings performed the
      echocardiograms. Infants with congenital anomalies and conditions, sepsis, IVH,
      and necrotizing enterocolitis were excluded. RESULTS: Out of 25 preterm infants,
      12 infants had hemodynamically significant PDA with left-to-right shunt. Two
      infants had small PDA and in 11 infants the ductus arteriosus was not patent. PDA
      infants had lower gestational age (P = 0.02) and birth weight (P = 0.03). Their
      Apgar scores (1 min) were lower (P = 0.03). The heart rate between the two groups
      differed, but was clinically within normal limits. Systolic (P = 0.05) and mean
      blood pressures (P = 0.04) were lower in the PDA group. A poor association
      between heart murmur, hyperdynamic chest and dorsalis pedis pulse, and the
      presence of PDA was revealed. CONCLUSION: Echocardiogram is required for early
      diagnosis of PDA in preterm infants, as clinical signs are not reliable in the
      first few days of life.

PMID- 15843269
TI  - Sudden infant death syndrome "gray zone" disclosed only by a study of the brain
      stem on serial sections.
AB  - Sudden infant death syndrome (SIDS) "gray zone" or borderline cases are defined
      as those cases in which it is difficult to establish whether the pathological
      findings are sufficiently severe to have caused the death. Examination of the
      brainstem in 103 cases of SIDS disclosed five SIDS "gray zone" cases in which
      only further investigations of serial sections successfully identified anatomico
      pathological findings that likely represent the morphological substrates for a
      sudden reflexogenic death. A complete autopsy was performed, including close
      examination of the brainstem and cardiac conduction system, according to our
      guidelines. Our five cases are consistent with the triple-risk model of SIDS, a
      hypothesis postulating an underlying biological vulnerability to exogenous
      stressors or triggering factors in a critical developmental period. Inflammatory
      infiltrates (cases 1 and 2), necrotic focus of the solitary tract (case 3),
      hemangioendothelioma (case 4) and mild pneumonia (case 5) alone might or might
      not have accounted for the sudden deaths, if it had not been for the location
      and/or concomitant presence of brainstem abnormalities that could have had a
      triggering role in causing the sudden death of these babies.

PMID- 15843270
TI  - Incidence and diagnosis of unilateral arterial cerebral infarction in newborn
      infants.
AB  - AIMS: Magnetic resonance imaging (MRI) is accepted as the gold standard for the
      diagnosis of arterial cerebral infarction (ACI), but few studies have reported
      the incidence of neonatal ACI based on MRI findings. We provide new population
      based epidemiologic and diagnostic data on all infants diagnosed between 1997 and
      2002 in our center with an MRI-confirmed diagnosis of unilateral neonatal ACI.
      RESULTS: Nine patients were identified, giving an incidence of 1:2300 unilateral
      ACIs in our inborn population. In all patients the middle cerebral artery was
      affected. Seven patients showed epileptic seizures, usually starting within the
      first 3 days of life. EEG was pathologic in all patients. Only three infarctions
      were diagnosed by ultrasound. Initial MRI established diagnosis of ACI in eight
      out of nine patients and subsequent MRI described the exact location of
      infarctions in all patients. Six out of nine patients developed hemiparesis and
      five had deficits in language development. There is a substantial need for
      special care facilities and long-term therapeutic interventions. CONCLUSIONS: The
      incidence of neonatal ACI is higher than previously reported. The sensitivity of
      early cerebral ultrasound for diagnosis of ACI is low. Seizures in the first 3
      days of life combined with pathologic EEG findings should lead to MRI, regardless
      of normal cerebral ultrasound.

PMID- 15843271
TI  - Non-hydropic intrauterine fetal death more than 5 months after primary parvovirus
      B19 infection.
AB  - AIMS: Clinical follow-up of possible fetal complications associated with maternal
      parvovirus B19 infection is usually recommended during the 2-3 months after
      primary infection. RESULTS: A case of late intrauterine fetal death associated
      with at least 5 months of maternal parvovirus B19 viremia and in the presence of
      B19 IgG and IgM is described. CONCLUSIONS: The time of clinical and laboratory
      follow-up after maternal parvovirus B19 infection may need to be revised if
      prolonged viremia is more common than previously described.

PMID- 15843272
TI  - A new syndrome of myopathy with muscle spindle excess.
AB  - Arthrogryposis may result from various neuromuscular or connective tissue
      disorders leading to in utero hypokinesia or akinesia and the prenatal
      development of joint contractures. We report the case of a preterm neonate born
      with arthrogryposis and flaccid quadriplegia that led to the diagnosis of
      myopathy with muscle spindle excess. The rare and unusual histopathologic
      abnormality associated with the myopathy illustrated in this case has been
      described in only three other cases in the medical literature. The concurrence of
      hypertrophic cardiomyopathy, arthrogryposis, and myopathy with muscle spindle
      excess suggests the presence of a newly described syndrome. This case clearly
      demonstrates that specific prenatal ultrasonographic findings combined with the
      presenting clinical manifestations should promptly raise the suspicion of a
      neuromuscular disorder.

PMID- 15843273
TI  - Causes of left ventricular hypertrabeculation/non-compaction in a neonate and her
      mother.

PMID- 15843277
TI  - Tumor necrosis factor-alpha and involuntary weight loss in elderly, community
      dwelling adults.
AB  - STUDY OBJECTIVE: To evaluate the association between involuntary weight loss and
      serum concentrations of tumor necrosis factor (TNF)-alpha in elderly, community
      dwelling adults. DESIGN: Cross-sectional, single-time point investigation.
      SETTING: Two primary care ambulatory clinics. SUBJECTS: Ambulatory adults aged 70
      years or older with involuntary weight loss of 2.27 kg (5 lbs) or more, or with
      stable weight (+/-0.91 kg [2 lbs]) for the 3 months before enrollment.
      MEASUREMENTS AND MAIN RESULTS: Ten subjects with weight loss (mean+/-SD-4.9+/-2.6
      kg) and 25 subjects with stable weight (+0.06+/-0.55 kg) were enrolled. The
      latter group was recruited to serve as a comparison group to the weight-loss
      group. Subjects donated a venous blood sample and were administered the Mini
      Nutritional Assessment at a single clinic visit. Serum concentrations of TNF
      alpha were measured by using enzyme-linked immunosorbent assay. The TNF-alpha
      concentrations were significantly higher in subjects with weight loss (mean+/-SD
      19.3+/-24.9 pg/ml) than in subjects with stable weight (mean+/-SD 1.1+/-2.0
      pg/ml, p<0.01). No relationship was found between the TNF-alpha concentration and
      the degree of weight loss expressed as a percentage of total body weight.
      CONCLUSION: Older adults with involuntary weight loss had increased circulating
      concentrations of TNF-alpha. Whether TNF-alpha plays a causal role in involuntary
      weight loss among older adults is unclear; however, this finding is consistent
      with those in other disease states associated with cachexia. Further research is
      necessary to clarify this relationship and to determine if pharmacotherapeutic
      interventions targeted at TNF-alpha can prevent or reverse involuntary weight
      loss and its associated morbidity and mortality.

PMID- 15843278
TI  - Impact of prophylactic amiodarone on length of hospital stay, stroke, and atrial
      fibrillation after cardiothoracic surgery.
AB  - STUDY OBJECTIVE: To evaluate the effect of prophylactic amiodarone on length of
      stay (LOS), postoperative stroke, and postoperative atrial fibrillation (POAF).
      DESIGN: Retrospective cohort study. SETTING: Hartford Hospital, Hartford,
      Connecticut. PATIENTS: Two thousand forty-six patients who underwent
      cardiothoracic surgery from February 1998-October 2003 (186 received amiodarone,
      1860 were controls). MEASUREMENTS AND MAIN RESULTS: Patients receiving any of the
      prophylactic amiodarone regimens used in the Atrial Fibrillation Suppression
      Trials (AFIST) I and II were matched (1:10 matching) for age, valvular surgery,
      history of atrial fibrillation, sex, beta-blocker intolerance, and preoperative
      digoxin therapy with patients not receiving amiodarone prophylaxis. The AFIST
      regimens consisted of oral amiodarone 6 g over 6 days and 7 g over 10 days,
      beginning on preoperative days 1 and 5, respectively, or a hybrid intravenous and
      oral loading regimen delivering amiodarone 7 g over 5 days. Mean+/-SD age of the
      patients was 68.9+/-9.8 years, 75% were men, and 21% had undergone valvular
      surgery. Patients receiving prophylactic amiodarone had a shorter LOS (8.6+/-6.0
      days) than controls (11.6+/-14.0 days, p=0.003) and a reduced frequency of POAF
      (23.1% vs 29.9%, p=0.05). Frequency of stroke was not significantly affected
      (2.2% vs 2.7% in the amiodarone vs control groups, p=0.61). CONCLUSION: Use of
      the prophylactic amiodarone regimens from the AFIST trials reduced LOS by 3.0
      days and frequency of POAF by 22.7%.

PMID- 15843279
TI  - Cost-efficacy of imatinib versus allogeneic bone marrow transplantation with a
      matched unrelated donor in the treatment of chronic myelogenous leukemia: a
      decision-analytic approach.
AB  - STUDY OBJECTIVE: To develop and populate a decision-analytic model for comparing
      the 2-year cost and efficacy of imatinib versus allogeneic bone marrow
      transplantation (BMT) with a matched unrelated donor in the treatment of a 35
      year-old man with newly diagnosed, Philadelphia chromosome-positive (Ph[+])
      chronic myelogenous leukemia (CML) in the chronic phase. DESIGN: Markov cohort
      analysis and first-order Monte Carlo microsimulation. MEASUREMENTS AND MAIN
      RESULTS: Direct medical costs were measured from the perspective of a third-party
      payer. Efficacy data and probabilities were obtained from survivability findings,
      most of which were derived from randomized controlled trials. We employed a 2
      year time horizon with 3-month treatment cycles. The comparator was BMT with a
      matched unrelated donor, and the base case was defined as a 35-year-old, Ph(+)
      man with newly diagnosed CML. The Monte Carlo microsimulation indicated that the
      incremental cost:efficacy ratio was -$5000 for imatinib (95% confidence interval 
      $70,000-84,000). Analysis of the cost-efficacy plane revealed that imatinib was
      dominant over BMT in 84.69% of cases, whereas BMT dominated imatinib in 0.76% of
      cases. Trade-offs were warranted in the remaining cases. Sensitivity analyses of
      costs and discount rates found these results to be generally robust. CONCLUSION:
      In most cases, imatinib was both less costly and more efficacious than BMT in the
      2-year treatment of CML. Results of this investigation should be viewed in the
      context of emerging long-term clinical data. These data are necessary to assess
      cost-efficacy beyond the short-term time horizon of this study.

PMID- 15843280
TI  - Effects of atorvastatin on low-density lipoprotein cholesterol phenotype and C
      reactive protein levels in patients undergoing long-term dialysis.
AB  - STUDY OBJECTIVES: To determine the effects of atorvastatin on low-density
      lipoprotein cholesterol (LDL) particle size and C-reactive protein (CRP)
      concentrations in patients undergoing long-term hemodialysis. Another objective
      was to compare the effects of atorvastatin on lipoprotein profiles as determined
      by direct versus indirect assessment of lipoprotein composition. DESIGN:
      Randomized, parallel-group substudy. SETTING: Two university-affiliated
      outpatient hemodialysis centers. PATIENTS: Nineteen patients with LDL levels
      above 100 mg/dl and with at least two cardiovascular risk factors. INTERVENTION:
      Patients were randomized in a 1:1 ratio to atorvastatin 10 mg/day or no treatment
      (control) for 20 weeks. MEASUREMENTS AND MAIN RESULTS: We compared the
      differences between LDL particle size and CRP levels at baseline and 20 weeks in
      the atorvastatin versus control groups. Baseline demographic characteristics were
      similar between the two groups. Atorvastatin therapy was associated with no
      change in mean LDL particle size (p=0.23) and with a 90% decrease in mean CRP
      level (p=0.52). When evaluated by standard chemical analysis, atorvastatin
      therapy reduced total cholesterol levels by 29% (p=0.025) and resulted in
      nonsignificant reductions in LDL, high-density lipoprotein cholesterol, and
      triglyceride levels. Treatment with atorvastatin was not associated with
      significant changes in lipoprotein profile as determined by nuclear magnetic
      resonance (NMR) spectroscopy. CONCLUSION: Treatment with atorvastatin did not
      affect LDL particle size but was associated with a sizable, yet nonsignificant,
      reduction in CRP concentrations. The drug had variable effects on lipoprotein
      concentrations as determined by chemical and NMR analytical methods. A larger
      study is necessary to provide definitive information on the effects of
      atorvastatin on LDL phenotype and CRP in patients with kidney disease.

PMID- 15843281
TI  - Low myopathy rates associated with statins as monotherapy or combination therapy
      with interacting drugs in a group model health maintenance organization.
AB  - STUDY OBJECTIVE: Because the risk for myopathy increases when 3-hydroxy-3
      methylglutaryl coenzyme A inhibitors (statins) are used with other agents known
      to inhibit cytochrome P450 3A4 in patients with dyslipidemia, we sought to
      quantify this risk in a diverse, real-world sample of patients receiving statin
      therapy. DESIGN: Retrospective chart review. SETTING: Kaiser Permanente Colorado
      (KPCO), a group model health maintenance organization with approximately 360,000
      members. PATIENTS: Four hundred sixty-eight patients who were identified as
      having a diagnosis of myopathy over a 4-year period using KPCO computerized data
      systems. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed to confirm
      myopathy cases associated with statin therapy. Of the 468 patients, 61 had
      received statin therapy before their diagnosis, and 41 (67%) of these patients
      had confirmed myopathy (documented creatine kinase level>or=1000 IU/L). The
      prevalence of myopathy was 0.12% with statin monotherapy and 0.22% with statins
      in combination with interacting drugs. Only 17 of the 41 (41%) patients had
      confirmed myopathy with no other plausible clinical explanation, such as a muscle
      injury. Increased risk of myopathy associated with statin therapy in combination
      with interacting drugs approached statistical significance (p=0.052) but was of
      minimal clinical significance. CONCLUSION: The prevalence of confirmed myopathy
      in patients receiving statin therapy is low (<1%). Combining statin therapy with
      interacting drugs (e.g., fibrates) was not associated with a clinically important
      increase in the prevalence of myopathy. The risk of developing myopathy during
      statin therapy is outweighed by the benefits derived from the therapeutic effects
      of the therapy.

PMID- 15843282
TI  - Validation of an insulin infusion nomogram for intensive glucose control in
      critically ill patients.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness, safety, and associated patient
      outcomes of a simplified, nurse-directed insulin nomogram designed to achieve
      intensive blood glucose level control (target range 90-144 mg/dl). DESIGN:
      Prospective study with a retrospective control group. SETTING: A medical-surgical
      intensive care unit (ICU) in a quaternary care, university-affiliated hospital in
      an urban center. PATIENTS: Eighty-six critically ill adult patients (aged>or=18
      yrs) requiring blood glucose control, with 42 in the retrospective control group
      and 44 in the prospective nomogram group. INTERVENTION: Control patients received
      insulin subcutaneously or intravenously based on ad hoc insulin sliding scales;
      nomogram patients received intravenous insulin at a rate specified by the
      nomogram, based on capillary blood glucose levels measured at the bedside.
      MEASUREMENTS AND MAIN RESULTS: Insulin infusion in the prospective patient group
      was titrated by the bedside nurse based on a predefined nomogram to attain the
      target blood glucose level. The retrospective control group was used as a
      comparison to assess the safety and effectiveness of the nomogram. Fewer patients
      in the nomogram (32%) than control (67%) group had a diagnosis of diabetes
      mellitus on admission. Overall, blood glucose levels in the nomogram group were
      within the target range 52% of the time versus 20% in the control group
      (p<0.001). Morning blood glucose levels were significantly lower compared with
      the control group (mean+/-SD 128+/-32 vs 176+/-50 mg/dl, p<0.001). Nomogram
      patients achieved target blood glucose levels faster than control patients
      (median 15 vs 66 hrs, p<0.0001). This improved blood glucose control remained
      statistically significant after adjusting for baseline differences in diabetes
      status. Hyperglycemia occurred less often in the nomogram than the control group
      (14% vs 53%, p<0.0001), and hypoglycemia occurred more often (3.8% vs 2.2%,
      p=0.004). The frequency of severe hypoglycemia was similar in both groups (0.2%
      vs 0.4%, p=NS). Such control required slightly more blood glucose checks/day in
      the nomogram group (7.1+/-1.5 vs 5.8+/-1.1, p<0.001). No significant reduction
      was observed in duration of vasopressor or antibiotic therapy or in length of
      stay in the ICU. CONCLUSION: This study demonstrated that intensive blood glucose
      control is achievable using a nurse-directed nomogram. This improved control was
      achieved, regardless of diabetes status of the patient, without substantially
      compromising safety or increasing resource use.

PMID- 15843283
TI  - Achieving cholesterol target in a managed care organization (ACTION) trial.
AB  - STUDY OBJECTIVES: To objectively compare the results of a collaborative approach
      using pharmacists with the results of usual care for achieving a low-density
      lipoprotein cholesterol (LDL) goal of 100 mg/dl or less in outpatients with
      documented coronary heart disease (CHD) who are not at goal, and to document the
      effect on LDL after removal of such a collaborative model from the study
      population. DESIGN: Prospective, multiclinic, controlled study. SETTING: Four
      clinics of a 19-clinic staff model health maintenance organization in Minneapolis
      and St. Paul, Minnesota. Two clinics treated the intervention patients, two the
      controls; one clinic for each group was suburban, and one for each was urban.
      PATIENTS: Four hundred eighty-one patients aged 18 years or older with CHD and
      whose LDL levels were not at goal. INTERVENTION: Clinical pharmacists implemented
      the physician-approved care plan for each intervention patient; activities
      included managing lipid-lowering drug therapy and educating patients on
      cardiovascular risk reduction. MEASUREMENTS AND MAIN RESULTS: Primary outcomes
      were changes in LDL level and the proportion of patients achieving goal LDL in
      the intervention versus the usual care (control) group. Secondary outcomes were
      the sustainability of the impact observed up to 18 months after discontinuation
      of the intervention. Mean+/-SD baseline LDL levels were 131+/-28 and 131+/-26
      mg/dl (p=NS) for the intervention and control groups, respectively. After a mean
      of 6.5 months follow-up, 107 (72%) patients in the intervention group and 61
      (18%) patients in the control group had attained their LDL goal (p<0.001). Mean
      LDL levels were reduced by 35.6 mg/dl (27.5%) and 6.7 mg/dl (4.6%) in the
      intervention and control groups, respectively (p<0.001). When the active program
      was discontinued, results of the 18-month follow-up indicated that 85 (65%)
      intervention patients remained at goal compared with 96 (42%) controls (p<0.001).
      CONCLUSION: This trial provides quantitative evidence to support the
      effectiveness of the collaborative approach as an intervention to optimize
      management of patients with CHD whose LDL levels are not at goal; this approach
      is specifically called for in the executive summary of the National Cholesterol
      Education Program Adult Treatment Panel III. Furthermore, this study documents
      both the magnitude and sustainability of the impact collaborative care models can
      have in managed care environments.

PMID- 15843284
TI  - Effects of a formulary change from granulocyte colony-stimulating factor to
      granulocyte-macrophage colony-stimulating factor on outcomes in patients treated
      with myelosuppressive chemotherapy.
AB  - STUDY OBJECTIVE: To evaluate the effects on efficacy and safety of a formulary
      change from granulocyte colony-stimulating factor (G-CSF) to granulocyte
      macrophage CSF (GM-CSF). DESIGN: Retrospective chart review. SETTING: Single
      center academic institution. PATIENTS: Fifty-six patients aged 18 years or older
      with breast cancer, lung cancer, melanoma, Hodgkin's lymphoma, or non-Hodgkin's
      lymphoma who developed neutropenia within 4 weeks after treatment with
      myelosuppressive chemotherapy and who had been given five or more doses of CSF as
      primary or secondary prophylaxis from January 1995-March 2002. Twenty-nine
      patients treated before January 2000 were given G-CSF; after the formulary change
      in January 2000, 27 patients were primarily given GM-CSF. MEASUREMENTS AND MAIN
      RESULTS: The primary efficacy end point was time to an absolute neutrophil count
      of 1.5x10(3)/mm3 or greater after treatment with CSF. Second and third efficacy
      end points, respectively, were frequency of febrile neutropenia and effect of CSF
      treatment on schedule and dose intensity of subsequent chemotherapy cycles.
      Primary and secondary safety end points, respectively, were frequency of adverse
      events and use of resources used to manage these events. The time to neutrophil
      recovery was similar with G-CSF and GM-CSF. Febrile neutropenia was more common
      in the patients given GM-CSF. Chemotherapy dose delays also were more common in
      patients treated with GM-CSF, as was the frequency of fever. Use of resources
      (platelet and red blood cell transfusions, intravenous antibiotics, and
      hospitalizations) was greater in the patients treated with GM-CSF. CONCLUSION:
      The formulary change to GM-CSF was associated with a higher frequency of febrile
      neutropenia, resultant chemotherapy dose delays, more adverse events, and greater
      use of resources to manage the adverse events. These results suggest that G-CSF
      and GM-CSF are not therapeutically equivalent, with G-CSF having a superior
      safety and efficacy profile for the prevention of chemotherapy-induced
      neutropenic events.

PMID- 15843285
TI  - Osteoporosis screening and education in community pharmacies using a team
      approach.
AB  - STUDY OBJECTIVES: To develop a model for osteoporosis screening and education in
      community pharmacies using a team approach, compare bone mineral density T-scores
      between quantitative ultrasound (QUS) and dual-energy x-ray absorptiometry (DXA),
      and determine patient satisfaction with this pharmacist-provided osteoporosis
      screening and education program. DESIGN: Prospective, cross-sectional study.
      SETTING: Community pharmacies and outpatient family medicine, internal medicine,
      and obstetrics and gynecology clinics in Amarillo, Texas. PATIENTS: Women aged 55
      years or older with no previous diagnosis of osteoporosis or osteopenia who had
      at least one additional risk factor for osteoporosis and had not been screened in
      the previous 3 years. INTERVENTION: Patients were referred from family medicine,
      internal medicine, and obstetrics and gynecology clinics to a community pharmacy.
      Osteoporosis screening using heel QUS and education regarding disease prevention
      and treatment were provided by pharmacists. Screening results, recommendations
      for confirmatory DXA, and potential treatments options were provided to the
      referring physicians. MEASUREMENTS AND MAIN RESULTS: A total of 100 patients
      (mean age 66.2+/-7.9 yrs) were enrolled in the study; three were subsequently
      excluded. Of the 97 study patients who were screened using QUS, 45 (46%) patients
      were at moderate risk (T-score<-1 to>-2.5) and nine (9%) were at high risk (T
      score<or=-2.5). Of 54 patients recommended for DXA referral, 20 (37%) completed
      the scan. All 20 were diagnosed with either osteopenia (9 patients [45%]) or
      osteoporosis (11 patients [55%]). Correlation was moderate between T-scores
      obtained by QUS and DXA of lumbar vertebrae 1-4 (r=0.45, p=0.026). Counseling
      regarding risk factors, screening results, smoking cessation, calcium intake,
      exercise, and caffeine intake was perceived by patients as valuable or highly
      valuable (medians for all items ranged from 4-5 on a 5-point Likert scale). Of 84
      patients assessed (13 were lost to follow-up), 81 (96%) said they would recommend
      this service to others. CONCLUSION: Osteoporosis screening and education in
      community pharmacies are effective in detecting undiagnosed disease and are
      perceived by patients as highly useful.

PMID- 15843286
TI  - Tactics for vascular protection after acute ischemic stroke.
AB  - BACKGROUND: The vascular events that happen during ischemic stroke worsen
      outcomes in patients by causing edema, hemorrhagic transformation, and general
      neurologic tissue compromise. In the past 2 decades, clinical trials in patients
      after ischemic stroke focused on neuroprotection, but these strategies have
      failed in providing actual benefit. Vascular protection represents a new field to
      be explored in acute ischemic stroke in order to develop new approaches to
      therapeutic intervention. PURPOSE: We identified tactics likely to provide
      vascular protection in patients with ischemic stroke. These tactics are based on
      knowledge of the molecular processes involved. SUMMARY OF REVIEW: The pathologic
      processes due to vascular injury after an occlusion of a cerebral artery can be
      separated into acute (those occurring within hrs), subacute (hrs to days), and
      chronic (days to mo). Targets for intervention can be identified for all three
      stages. In the acute phase, superoxide is the predominant mediator, followed by
      inflammatory mediators and proteases in the subacute phase. In the chronic phase,
      proapoptotic gene products have been implicated. Many already-marketed
      therapeutic agents (statins, angiotensin modulators, erythropoietin, minocycline,
      and thiazolidinediones), with proven safety in patients, have been shown to have
      activity against some of the key targets of vascular protection. CONCLUSION:
      Currently available pharmacologic agents are poised for clinical trials of
      vascular protection after acute ischemic stroke.

PMID- 15843287
TI  - Duloxetine: a dual serotonin-norepinephrine reuptake inhibitor for treatment of
      major depressive disorder.
AB  - The burden of mental illness has been underestimated worldwide. Depression was
      the fourth leading cause of disease burden in the world in 1990 and is projected
      to be the second leading cause of disability by 2020. It is a leading cause of
      morbidity and mortality in the United States, costing billions of dollars
      annually in direct and indirect medical costs and losses in productivity.
      Patients with major depressive disorder (MDD) may experience both psychological
      and medical complaints, including somatic sensations or pain. Some
      antidepressants have been shown to treat chronic pain syndromes, but despite the
      variety of antidepressants available in the United States, only 65-70% of
      patients respond to initial antidepressant treatment. Treatments are limited by
      delayed onset of antidepressant effects, side effects, partial response, and
      treatment resistance. Duloxetine, approved by the U.S. Food and Drug
      Administration for the treatment of MDD, is a reuptake inhibitor at serotonergic
      and noradrenergic neurons and appears to have low affinity for other
      neurotransmitter systems. In clinical trials, duloxetine was effective for the
      treatment of MDD and was well tolerated. Further study is needed to compare its
      efficacy with that of other antidepressants, to clarify effects on somatic
      symptoms, and to assess potential adverse cardiovascular and sexual side effects.
      Duloxetine is also approved for the management of diabetic peripheral neuropathic
      pain and is under investigation for the treatment of stress urinary incontinence
      in women.

PMID- 15843288
TI  - The use of tricyclic antidepressants and selective serotonin reuptake inhibitors
      in women who are breastfeeding.
AB  - Postpartum depression is a well-recognized psychiatric condition that has gained
      increased attention over the past decade due to several nationally publicized
      tragedies. Medical management of this condition in women who are breastfeeding
      provides a unique challenge to health care professionals who may seek to maintain
      a fine balance between limiting the infant's exposure to hormone-altering drugs
      and maintaining the benefits of breastfeeding. No controlled trials have examined
      antidepressant therapy in nursing women; however, numerous case reports and case
      series have been published. Relatively few serious adverse effects have been
      reported. Although tricyclic antidepressants have been the treatment of choice in
      the past, selective serotonin reuptake inhibitors are gaining popularity due to
      their superior safety profiles. Of all the agents reviewed in the literature,
      sertraline was the most prescribed, and no adverse effects were reported.
      Therefore, this agent would be a good first choice for treatment-naive women. For
      treatment of postpartum depression in women with a history of successfully
      treated depression, the most practical approach may be to continue therapy with
      the previously effective agent. Treatment should be maintained at the lowest
      effective dosage to minimize infant exposure. Both mother and child should be
      closely monitored; in addition, collaboration between the prescribing physician
      and the child's pediatrician is essential.

PMID- 15843289
TI  - Fatal amphotericin B overdose due to administration of nonlipid formulation
      instead of lipid formulation.
AB  - The toxicity of amphotericin B deoxycholate has led to increased preference for
      lipid formulations with more favorable safety profiles. However, the primary use
      of lipid formulations is cost prohibitive, and many hospital formularies list
      both lipid and nonlipid formulations. A dispensing and administration error that
      caused amphotericin B deoxycholate to be given instead of liposomal amphotericin
      B related in a fatality. Measures to prevent confusion and aid in understanding
      the differences between lipid and nonlipid formulations of amphotericin B should
      be implemented.

PMID- 15843290
TI  - Amiodarone use in patients with documented allergy to iodine-containing
      compounds.
AB  - The popularity of amiodarone has grown due to its effectiveness in converting
      arrhythmia and its formulation availability. Formulations of the drug also
      contain iodine; the iodine content is 75 mg in a 200-mg tablet of amiodarone and
      18.7 mg/ml in the intravenous solution. Approximately 10% of the iodine content
      of oral amiodarone is released into the circulatory system and may increase the
      risks of hypersensitivity reactions in iodine-sensitive patients. Documented
      allergies to contrast media or shellfish should not imply that a patient is
      allergic to iodine. Reactions to contrast media are likely due to the high
      osmolar or ionic content of the dye. The primary allergen in shellfish that
      stimulates allergic reactions is tropomyosin. Although amiodarone can cause
      thyroid disorders due to the high iodine load delivered to the body with each
      dose, no known association exists between amiodarone and reactions to contrast
      media or shellfish. Three patients whose medical charts listed an allergy to
      iodine were administered amiodarone for chemical cardioversion of arrhythmia to
      normal sinus rhythm. No anaphylactic or anaphylactoid reactions were observed in
      any of the patients during oral or intravenous amiodarone administration. In
      patients with true iodine hypersensitivity, however, the potential for such
      reactions exists.

PMID- 15843291
TI  - Exacerbation of panic disorder with rifampin therapy in a patient receiving
      citalopram.
AB  - Citalopram, a selective serotonin reuptake inhibitor, is used in the management
      of anxiety disorders. A 55-year-old man receiving citalopram for panic disorder
      reported a decrease in the agent's therapeutic efficacy when rifampin was started
      for osteomyelitis. His condition improved when the rifampin was stopped. Rifampin
      is known to induce the metabolism of cytochrome P450 3A4 substrates and thus
      plays a role in several drug-drug interactions. We suspect that the efficacy of
      citalopram was blunted with the concurrent use of rifampin. To our knowledge,
      only one other case of an interaction of rifampin with a selective serotonin
      reuptake inhibitor is described in the literature. Clinicians should monitor all
      drugs and dietary supplements that patients with psychiatric conditions take,
      regardless of the indication, intended purpose, or prescriber. This is especially
      important, however, for a drug that is pivotal to a patient's well-being; its
      therapeutic effect should be carefully monitored when any new drug is added or a
      change in the dosage of a concurrent drug is made.

PMID- 15843292
TI  - Neonatal effects of breast cancer chemotherapy administered during pregnancy.
AB  - A human fetus is most susceptible to teratogenic agents during the first
      trimester of pregnancy. Cyclophosphamide and doxorubicin are pregnancy category D
      agents; however, potential benefits may warrant treatment with these agents
      during pregnancy under special circumstances. During her first trimester of
      pregnancy, a 37-year-old Caucasian woman was diagnosed with stage IIB
      infiltrating ductal carcinoma in situ (breast cancer) that was estrogen and
      progesterone receptor negative and human epidermal growth factor receptor-2
      positive. The patient was treated with doxorubicin and cyclophosphamide in the
      second and third trimesters and delivered a premature baby boy at 31 weeks'
      gestation. The neonate was intubated on delivery because of respiratory distress
      and failure; however, no physical anomalies were observed. He had neutropenia and
      anemia, quite possibly as a result of his mother's chemotherapy 1 week before
      delivery. He was prophylactically treated for sepsis, but all cultures were
      negative. The infant grew and developed normally during his first year of life
      and remained in good health. An objective causality assessment revealed that it
      was probable that the infant's adverse events (prematurity, neutropenia, and
      anemia) were related to his mother's doxorubicin and cyclophosphamide therapy;
      however, these were the only adverse events potentially linked to in utero
      exposure to chemotherapy during the second and third trimesters. Due to the
      special considerations of both mother and infant, optimal treatment for patients
      with pregnancy-associated breast cancer requires the expert opinion of a
      multidisciplinary care team.

PMID- 15843293
TI  - Increasing warfarin dosage reductions associated with concurrent warfarin and
      repeated cycles of 5-Fluorouracil therapy.
AB  - Concurrent use of warfarin and 5-fluorouracil has resulted in elevated
      international normalized ratios (INRs). Although this drug interaction is well
      established in the literature, we found no documented cases that address its
      effects on anticoagulation parameters in patients requiring repeated cycles of 5
      fluorouracil and continuous warfarin therapy. We describe the effect of multiple
      cycles of 5-fluorouracil administration in a patient receiving warfarin therapy.
      The patient's INR increased 11-14 days after each cycle of chemotherapy with 5
      fluorouracil and leucovorin. In addition, she required additive reductions of 33
      42% in her weekly warfarin dose with each chemotherapy cycle to maintain a
      therapeutic INR (goal range 2.0-3.0). After three cycles of chemotherapy over a
      10-week period, the patient's dosage requirements returned to her baseline level
      (before treatment with 5-fluorouracil and leucovorin had started). Pertinent
      literature was reviewed to provide supporting evidence for the mechanism and
      clinical implications of the drug interaction. Based on this report and previous
      case reports, caution is advised when concurrent warfarin and 5-fluorouracil are
      prescribed. In addition, patients should be closely monitored for a possible
      delayed interaction that may occur with each repeated cycle of 5-fluorouracil
      chemotherapy.

PMID- 15843294
TI  - Probable topical permethrin-induced neck dystonia.
AB  - A 28-year-old Caucasian man who applied topical 5% permethrin cream once for the
      treatment of scabies infestation experienced a severe dystonic reaction on the
      left side of his neck. Assessment of causality using the Naranjo algorithm
      revealed a probable relationship between this adverse drug event and application
      of topical permethrin. Dystonic or musculoskeletal adverse reactions, including
      muscle spasms, have been reported with pyrethroid insecticides only after
      inappropriate occupational dermal exposure. These reported reactions occurred 4
      48 hours after exposure and lasted from a few days to a few weeks. The mechanism
      behind these adverse effects may be related to permethrin's ability to delay
      sodium channel closure within nerve cells. This may result in a lowered threshold
      of nerve fibers to activation of further action potentials, leading to repetitive
      firing and hyperexcitation of the nervous system. Clinicians should be aware of
      this rare but potential adverse effect of permethrin.

PMID- 15843299
TI  - Gender identity and the self: I. Gender formation in general and in masculinity.

PMID- 15843300
TI  - Gender identity and the self: II. Femininity, homosexuality, and the theory of
      the self.

PMID- 15843301
TI  - Correspondence between an Elizabethan woman and her psychoanalyst: Beatrice on
      the couch.

PMID- 15843305
TI  - Discovery of the mother's body and the creation of the daughter's subjectivity.

PMID- 15843306
TI  - Echo in the darkness.

PMID- 15843308
TI  - The Other of the body and the language of the margins.

PMID- 15843309
TI  - Pothos: longing for place. Commentary on "the Other of the body and the language
      of the margins".

PMID- 15843310
TI  - Attachment mechanisms and the bridging of science and religion: the challenges of
      anthropomorphism and sect-ism.

PMID- 15843311
TI  - Terror of desire: the etiology of eating disorders from an attachment theory
      perspective.

PMID- 15843312
TI  - My intuitometer: experience and inference.

PMID- 15843313
TI  - The vertical split in neurosis and psychosis: motor acts and the infrastructure
      of agency.

PMID- 15843314
TI  - The shadow of movement in psychoanalysis.

PMID- 15843315
TI  - "How could you!": self-righteousness under scrutiny in a therapy group.

PMID- 15843319
TI  - Prediction of suicide revisited: a brief methodological note.

PMID- 15843320
TI  - Aspects of suicidal behavior, depression, and treatment in college students:
      results from the spring 2000 national college health assessment survey.
AB  - The National College Health Assessment Survey (NCHA), sponsored by the American
      College Health Association, measured depression, suicidal ideation, and suicide
      attempts among 15,977 college students in the academic year 1999-2000. Similar to
      the National College Health Risk Behavior Survey, conducted by the Centers for
      Disease Control and Prevention in 1995, 9.5% of students reported that they had
      seriously considered attempting suicide and 1.5% of students reported that they
      had attempted suicide within the last school year. The NCHA findings show a
      relationship between suicidal behavior and depressed mood. Depressed mood,
      difficulties of sexual identity, and problematic relationships all increase the
      likelihood of vulnerability to suicidal behavior. Less than 20% of students
      reporting suicidal ideation or attempts were receiving treatment.

PMID- 15843321
TI  - The mediating roles of anxiety depression, and hopelessness on adolescent
      suicidal behaviors.
AB  - The purpose of this study was to explore the roles of anxiety, depression, and
      hopelessness as mediators between known risk factors and suicidal behaviors among
      1,287 potential high school dropouts. As a step toward theory development, a
      model was tested that posited the relationships among these variables and their
      effects on suicidal behaviors. Structural equation models, estimated separately
      by gender, revealed support for the model, and substantial similarities between
      males and females. The results showed direct effects of depression and
      hopelessness on suicidal behaviors for males, and direct effects of hopelessness,
      but not depression, for females. For both males and females, anxiety was directly
      linked to depression and hopelessness; drug involvement had both direct and
      indirect effects on suicidal behavior. As hypothesized, lack of family support
      showed indirect influences on suicidal behaviors through anxiety for both males
      and females. The results have important implications for future model development
      regarding adolescent suicidal behaviors.

PMID- 15843322
TI  - The relationship between seriously considering, planning, and attempting suicide
      in the youth risk behavior survey.
AB  - The assumed ordinal relationship between seriously considering, planning, and
      attempting suicide in the 1999 Youth Risk Behavior Survey was examined by
      constructing a trajectory that identified all possible response patterns among
      the four questions measuring suicidal activity. Statistical analysis tested for
      differences in frequency of risk behaviors across levels of the trajectory.
      Overall, the trajectory provided insight to the progression of adolescent
      suicidal activity and demonstrated usefulness as a measure of suicidal intent.
      Significant differences between means of dependent variables at each level of the
      normative trajectory supported the hypothesis that frequency of risk behaviors
      increases monotonically with successive suicidal thought and behavior.

PMID- 15843323
TI  - Schizophrenia and deliberate self-harm: a systematic review of risk factors.
AB  - Deliberate self-harm (DSH) is a strong predictor of suicide in schizophrenia. The
      aim of this review was to identify risk factors for DSH in schizophrenia. This
      systematic review of the international literature examined cohort and case
      control studies of patients with schizophrenia or related diagnoses that reported
      DSH as an outcome. Studies were identified by searching electronic databases and
      reference lists, and by consulting international experts. Fourteen studies met
      the eligibility criteria. Of the 29 variables examined by two or more studies,
      five (past or recent suicidal ideation, previous DSH, past depressive episode,
      drug abuse or dependence, and higher mean number of psychiatric admissions) were
      associated with an increased risk of DSH, and one (unemployment) was associated
      with a reduced risk. Schizophrenic patients with these risk factors need careful
      follow-up and monitoring, with treatment of any associated comorbid depression or
      drug abuse. Large, prospective studies of DSH in schizophrenia are needed to
      further define risk factors and to build on the findings of this review.

PMID- 15843325
TI  - Intimate femicide followed by suicide: examining the role of premeditation.
AB  - People who kill others rarely kill themselves afterwards. When they do, they are
      more likely to have killed someone with whom they were intimate. Two broad types
      of suicidal killers have been identified in research that presumes varying
      degrees of premeditation. Using data on over 700 intimate femicides, the role of
      premeditation in cases of intimate femicide-suicide compared to killings that do
      not culminate in a suicide was examined. My results show that premeditation is
      more likely to occur in cases involving the offenders' suicide, but that evidence
      of premeditation varies depending upon the type of suicidal killer.

PMID- 15843324
TI  - Demographic, criminal, and psychiatric factors related to inmate suicide.
AB  - A review of 19 studies suggests that it may be feasible to identify prisoners
      with suicide risk on the basis of demographic, psychiatric, and criminal
      characteristics. The present study aimed to identify combinations of
      characteristics that are capable of identifying potential suicide victims.
      Characteristics of 95 suicide victims in the Dutch prison system were compared
      with those of a random sample of 247 inmates in ten jails. Combinations of
      indicators for suicide risk were also tested for their capability of identifying
      209 suicides in U.S. jails and 279 prison suicides in England and Wales. A
      combination of six characteristics (age 40+, homelessness, history of psychiatric
      care, history of drug abuse, one prior incarceration, violent offence) was
      capable of correctly classifying 82% of the Dutch suicide victims (82%
      specificity). Less powerful combinations correctly classified 53% of the U.S.
      suicides and 47% of the U.K. suicides. It is concluded that a set of demographic
      and criminal characteristics and indicators of psychiatric problems is useful for
      the identification of suicide risk in jails and prisons.

PMID- 15843326
TI  - Correlates of suicide in the older adult population in Quebec.
AB  - This study was undertaken to describe the characteristics of adults aged 60 years
      and over who committed suicide in Quebec in 1998-1999. In this study, 42.6% of
      the suicide cases presented mental disorders at the time of their death, mainly
      depression. Sixty-five (65.3%) percent of the suicide cases would have been
      considered as having a mental health disorder if sub-threshold depression cases
      were included. Only 27.7% of the cases did not express any idea of death during
      the 6-month period preceding their suicide. One interesting finding was that
      53.5% of the suicide cases consulted a general practitioner or specialist during
      the 2-week period preceding their death. Our results showed that only 8.1% had a
      severe level of functional limitations at the time of their death. This result
      leads us to interpret with caution the conclusion of some studies suggesting that
      physical frailty is a major causal factor associated with suicide among the
      elderly.

PMID- 15843327
TI  - Gender differences in predictors of suicidal thoughts and attempts among homeless
      veterans that abuse substances.
AB  - This study of 315 male and 310 female homeless military veterans in a V.A.
      inpatient program designed to treat substance abusers, many of whom also suffer
      psychiatric disorders, was designed to examine gender differences in factors
      associated with the odds of having suicidal thoughts, and of attempting suicide,
      in comparison to being nonsuicidal. A maximum likelihood estimation multinomial
      logistic regression showed childhood and current sexual and physical abuses,
      depression, fearfulness, relationship problems, limited social support, and low
      self-esteem was more strongly associated with suicidal thoughts and attempts for
      women than for men veterans. Extent of alcohol and other drug abuse, aggression,
      resilience, self-efficacy, combat exposure, combat-related PTSD, and work
      problems were more strongly associated with suicidal thoughts and attempts for
      men than for women. Implications of these findings for V.A. programs are
      discussed.

PMID- 15843329
TI  - How I read.

PMID- 15843330
TI  - Suicide in the media: a quantitative review of studies based on non-fictional
      stories.
AB  - Research on the effect of suicide stories in the media on suicide in the real
      world has been marked by much debate and inconsistent findings. Recent narrative
      reviews have suggested that research based on nonfictional models is more apt to
      uncover imitative effects than research based on fictional models. There is,
      however, substantial variation in media effects within the research restricted to
      nonfictional accounts of suicide. The present analysis provides some explanations
      of the variation in findings in the work on nonfictional media. Logistic
      regression techniques applied to 419 findings from 55 studies determined that:
      (1) studies measuring the presence of either an entertainment or political
      celebrity were 5.27 times more likely to find a copycat effect, (2) studies
      focusing on stories that stressed negative definitions of suicide were 99% less
      likely to report a copycat effect, (3) research based on television stories
      (which receive less coverage than print stories) were 79% less likely to find a
      copycat effect, and (4) studies focusing on female suicide were 4.89 times more
      likely to report a copycat effect than other studies. The full logistic
      regression model correctly classified 77.3% of the findings from the 55 studies.
      Methodological differences among studies are associated with discrepancies in
      their results.

PMID- 15843331
TI  - The science of public messages for suicide prevention: a workshop summary.
AB  - There is minimal guidance for efforts to create effective public messages that
      increase awareness that suicide is preventable. To address this need, several
      agencies in the U.S. Department of Health and Human Services and the Annenberg
      Foundation convened a workshop consisting of suicide prevention advocates and
      persons with expertise in public health evaluation, suicide contagion, decision
      making, and marketing. "Logic models" were used to define intended messages and
      audiences, assumed mechanisms of change, and outcomes. This summary describes
      some of the challenges and opportunities identified by workshop participants in
      evaluating public awareness campaigns in suicide prevention, technical assistance
      needs, and a proposed research agenda.

PMID- 15843332
TI  - Suicide compared to other causes of mortality in physicians.
AB  - Physicians frequently are early adopters of healthy behaviors based on their
      knowledge and economic resources. The mortality patterns of physicians in the
      United States, particularly suicide, have not been rigorously described for over
      a decade. Previous studies have shown lower all-cause mortality among physicians
      yet reported conflicting results about cause-specific mortality such as suicide.
      In this study, we compared all-cause and cause-specific mortality in a sample of
      physicians to the age-gender matched general U.S. population from 1948 through
      1998. We also compared the mortality experience across medical specialties. The
      risk of all-cause mortality was 56% lower than expected in men, and 26% lower in
      women, compared to the general population. Standardized mortality ratios (SMRs)
      were markedly lower for diseases strongly linked to smoking, e.g., cardiovascular
      diseases, respiratory diseases, and lung cancer. Suicide was the only cause of
      death where risk was greater than the general population. Overall, we found that
      physicians are at substantially lower risk of dying compared to the general
      population for all causes of death except suicide. The findings for suicide are
      strikingly different than other causes of death and should provide impetus for
      new research on the mental health of physicians.

PMID- 15843333
TI  - Youth suicide prevention: a survey of public school superintendents'
      acceptability of school-based programs.
AB  - From a random sample of members of the 2000-2001 membership directory of the
      American Association of School Administrators (AASA), public school
      administrators' acceptability ratings of three school-based programs for the
      prevention of adolescent suicide were examined. A total of 210 (46%) respondents
      examined a description of a suicide prevention program and completed a measure
      designed to evaluate the acceptability of suicide prevention programs. Three
      suicide prevention programs were evaluated for their acceptability, and included:
      (a) school-wide curriculum-based programs presented to students; (b) in-service
      presentations to school staff; and (c) self-report screening programs for
      students. The results indicated that superintendents rated the staff in-service
      training and curriculum-based programs as significantly more acceptable than the
      school-wide screening program. In addition, the school-wide screening program was
      rated as significantly more intrusive by school psychologists than the staff in
      service training or curriculum-based prevention programs. Limitations of the
      study and future research directions are discussed.

PMID- 15843334
TI  - Young peoples' opinions about the causes of, and solutions to, New Zealand's high
      youth suicide rate.
AB  - In response to an open-ended question about the causes of New Zealand's high
      youth suicide rate, 384 young adults most commonly cited pressure to conform and
      perform, followed by financial worries, abuse and neglect, problems with alcohol
      or drugs, and boredom. Depression was cited by 5 percent and mental illness by
      only 1 percent. Recommended solutions included crisis support services located in
      schools and youth centers, youth activities, educational programs to assist young
      people to discuss feelings and to bolster self-esteem, and financial aid. Neither
      increasing mental health services, nor reducing media coverage of suicides, was
      considered to be a solution.

PMID- 15843335
TI  - Testing a model of suicide ideation in college students.
AB  - This study examined several risk factors-negative life events (NLE),
      hopelessness, and depressive symptoms-believed to commonly precipitate suicide
      ideation in college students. A total of 345 undergraduates participated in the
      study. Students completed four self-report questionnaires. Hierarchical
      regression analyses were used to construct a risk model of suicide ideation. This
      study confirmed depressive symptoms and hopelessness as predictors of suicide
      ideation in college students; however, NLE impacted suicidal thoughts through
      hopelessness and depressive symptoms. Interestingly, depressive symptoms exerted
      a stronger influence on suicide ideation than hopelessness. Hopelessness served
      as a partial mediator in the relationship between NLE and depressive symptoms;
      however, depressive symptoms fully mediated the relationship between NLE and
      hopelessness. Clinical implications for understanding suicide risk in college
      students are discussed.

PMID- 15843336
TI  - Is suicide ideation a surrogate endpoint for geriatric suicide?
AB  - The present study explored the validity of treating suicide ideation as a
      surrogate endpoint that can serve as a proxy for suicide in clinical intervention
      research with suicidal seniors. Two criteria; that suicide ideation is modulated
      by the proposed intervention and that modulation of suicide ideation leads to a
      quantitative reduction in suicide rates, were the focus of this review. A series
      of literature searches of the PsychINFO and Medline databases were conducted on
      the terms geriatric, elderly, seniors, suicide, self-destruction, clinical,
      randomized, trial, treatment, intervention , and ideation . Articles were
      analyzed if they provided sufficient information to examine whether an
      intervention effectively led to a reduction in suicide ideation among seniors.
      Two hundred and eight articles were considered for potential inclusion in this
      study, with 19 articles meeting final inclusion criteria. The articles reviewed
      were divided into three broad categories: articles supporting suicide ideation as
      a surrogate endpoint for geriatric suicide ( n = 6); those not supporting this
      hypothesis ( n = 1); and those providing insufficient information to test the
      hypothesis ( n = 12). The present analysis provided modest evidence for suicide
      ideation as a surrogate endpoint for geriatric suicide, due, in part, to a
      paucity of randomized controlled trials of treatment interventions for suicidal
      seniors, thus demonstrating a clear need for research in this area. Implications
      of utilizing surrogate endpoints in suicide research are discussed.

PMID- 15843337
TI  - Are adoptees at increased risk for attempting suicide?
AB  - This study addresses the controversy of whether adopted adolescents are at risk
      for more mental health problems than the nonadopted and specifically evaluates
      differences in suicide ideation and depression. Same gender comparisons were made
      between 346 adopted adolescents and nearly 14,000 others living with biological
      parents, with nationally representative data from the National Longitudinal Study
      of Adolescent Health. Results showed few divergences in suicide ideation,
      attempts, and depression between adopted and nonadopted adolescents and young
      adults. Future studies employing this same dataset will need to pay closer
      attention to the high percentages of respondents adopted by blood relatives,
      which only became known with the collection of the Wave III Add Health data.

PMID- 15843338
TI  - Historical change of suicide seasonality in the canton of zurich, Switzerland.
AB  - Current research is yielding an increasingly heterogeneous picture of suicide
      seasonalities: They seem to depend on methods and, moreover, they seem to have
      smoothed in recent decades. This work examines the latter issue by comparing
      suicide seasonalities in the canton of Zurich, Switzerland, in the 16 th -18 th
      centuries, 1901-1920 and 1969-94. The results indicate shifts of peaks and lows
      on suicide seasonalities over the centuries, with a smoothing of seasonalities
      toward the 21 th century. The recent period does not show any suicide seasonality
      at all. The canton of Zurich seems to be ahead of the general trend found in
      other regions of Switzerland.

PMID- 15843339
TI  - Prospective cohort study of stress, life satisfaction, self-rated health,
      insomnia, and suicide death in Japan.
AB  - The association between many psychosocial factors and risk of suicide was
      examined. A cohort was conducted over 14 years of follow up among the general
      population (15,597 people) in Japan. A baseline survey of psychosocial
      characteristics was conducted by self-administrated questionnaire. The relative
      risks of occasional emotional stress, difficulty maintaining sleep, and reporting
      unhealthy as their self-rated health are 3.2 (95% CI: 1.3, 7.6), 2.4 (95% CI:
      1.3, 4.3) and 2.6 (95% CI: 1.1, 6.2), respectively. The importance of these
      observations lie in its potential for improving physician and public awareness of
      psychosocial factors as an early indication of mental health morbidity.

PMID- 15843340
TI  - [The genetic diversity of the second exon about SLA-DQB in some Chinese native
      pigs].
AB  - Polymorphism of the second exon about SLA-DQB genes in some Chinese native pigs
      was investigated employing PCR-SSCP analysis and DNA cloning sequencing. Combined
      with the sequences in GenBank, 73 new alleles were gained, among them function
      alleles of SLA-DQB were sixty-eight, five alleles of pseudogene (SLA-DXB) were
      gained. There were disequilibrium distribution of the alleles in all breeds, the
      same allele was shared by most breeds. C08 allele existed in 11 breeds of six
      groups and in the wild pigs of Yunnan and Sichuan province, and its frequency
      reached 55.10%. More than five sequences were found in each individual,
      suggesting duplication in these loci examined, there were three copies about SLA
      DQB genes. The variable sites based on nucleotide and amino acids reached to
      eighty-one and forty-nine, respectively. The values of allelic diversity
      (H=0.889) and the nucleotide diversity (Pi=0.047) were revealed very high, from
      both values of H and Pi were higher in the beta pleated sheet region than those
      in alpha helix region in Chinese native pigs. In general, values of H and Pi in
      Huanan pigs and Xinan pigs were higher, vice versa in Tibet pigs. The genetic
      distance within group were showed the same order as comparison Pi values, hence
      we concluded the different rate of nucleotide substitution were positive
      correlated with the degree of nucleotide diversity in Chinese domestic groups.
      The genetic distances about SLA-DQB gene between groups were detected as follow:
      the great genetic distance were existed between the Jianghai and Huabei groups,
      and the smallest genetic distance were existed between the Huazhong and Gaoyuan
      groups.

PMID- 15843341
TI  - [Relationship of activation of Tos17 and rice adult plant resistance to bacterial
      blight].
AB  - to investigate whether rice adult plant resistance (APR) is related to activation
      of long terminal repeat (LTR) retroelements, polymorphism of LTR retroelemnts
      Tos17 are studied using SSAP (Sequence-Specific Amplification Polymorphism) in
      seedlings and adult plants of rice cultivar Wase Aikoku 3 inoculated with
      Xanthomonas oryzae pv. Oryzae, water and those untreated. Of 2000 fragments
      detected, 9 and 2 are activated in seedlings and adult plants induced by
      development, respectively; each 3 fragments are activated in seedlings and adult
      plants induced by pathogen, respectively. The number of activated Tos17 induced
      by development is more in seedlings than that in adult plants while it is equal
      due to pathogen induction in seedlings and adult plants, suggest that the
      activation of Tos17 induced by development probably associate with rice APR to
      bacterial blight.

PMID- 15843342
TI  - [The application of interphase fluorescence in situ hybridization to the
      diagnosis of X chromosomal count abnormality in ovarian carcinoma cell].
AB  - To study the technique of fluorescence in situ hybridization (FISH) and its
      application value in the diagnosis of sex chromosomal count abnormality in
      ovarian carcinoma cell. Biotin labeled alpha satellite X chromosome DNA(pBamX7)
      probe was hybridized with pre-treated slides of ovarian carcinoma cell interphase
      nucleus in 18 cases of ovarian carcinoma specimens. The slides were treated with
      Avidin-FITC and Anti-avidin, amplified with an additional layer and counter
      stained with PI in antifade solution. The hybridization signals as well as
      interphase nucleus settings were observed with WIB filters under fluorescence
      microscope Olympus AX-70, and the number of interphase nucleus in the ovarian
      carcinoma cell was counted. It was observed under the microscope that the Biotin
      labeled pBamX7 probe showed green hybridization signals. Cytoplasm counter
      stained with PI showed reddish orange. Increased chrosome X copy number was
      observed in 11/18(61%) ovarian carcinoma specimens, of which the rest 7 (39%) had
      no increase of chrosome X copy number. Gain of X chrosome had a certain incidence
      in ovarian cancers, which played a role in the recurrence and development of
      ovarian cancers. Its significance needs further investigation.

PMID- 15843343
TI  - [The C224T polymorphism in the cathepsin D gene is not associated with sporadic
      Alzheimer's disease in Chinese].
AB  - Cathepsin D is the major lysosomal/endosomal aspartic protease and exhibits beta-
      and gamma-secretase-like activity in vitro. Data from German suggest that the
      C224T polymorphism in the Cathepsin D gene (CTSD) exon 2 is strongly associated
      with the risk for Alzheimer's disease (AD). Meanwhile other studies have not been
      able to replicate the result. It's necessary to determine the genotype of the
      polymorphism in CTSD in Chinese sporadic AD patients and age-matched controls
      with normal cognition and examine possible association of the polymorphism with
      the disease. We find no strong evidence of association between the CTSD C224T
      polymorphism and Chinese sporadic AD. Whereas there may be a weak synergistic
      interaction between ApoE epsilon4 and CTSD T allele.

PMID- 15843344
TI  - [Research on gene transfer by spermatozoa].
AB  - Incubate golden hamster spermatozoa and NF (kappa) B-luc(+) in co-culture and
      liposome mediated methods, and then process the IVF with oocytes, And two groups
      of samples were detected by PCR, Southern Blot and FISH. Analyzed the relative
      data by statistics. The results showed that spermatozoa of Golden hamster
      epididymis can take the foreign DNA voluntarily, and the foreign DNA exist in the
      head of the spermatozoa can enter into zygotes by IVF. The exist of liposome can
      improve the foreign gene transfect ratio and transgenic ratio.

PMID- 15843345
TI  - [Report on 16 rare species of human chromosomal].
AB  - By examining the lymphocytic chromosomes of peripheral blood from patients with
      amenorrhea, spontaneous abortion and stillbirth history, .the 16 rare species of
      human chromosomal abnormal karyotypes were discovered. They were
      46,XY,t(6;11)(q25;p15);46,XY,inv(3)(p25;q29);46,XY,t(7;18)(q10;p10);46,X,t(X;13)(
      24;q14);46,XY,t(4;7)(q33;q22);46,XY,t(8;15)(q24;q15);46,XY,t(2;17)(q33;q25);46,XX
      t(4;7)(q34;q11);46,XX,t(1;3)(p36;p23);46,XX,t(4;6)(q35;p11);46,X,inv(X)(q22;q28);
      6,XX,t(7;10)(p11;q26);46,XX,t(3;6)(p21;q23);46,XX,t(8;16)(p21;p13);46,XX,t(8;9)(q
      1;q34);46,XY,t(17;22)(q21;q11). Their clinical situation were described.
      Discussion on the relationship between the chromosomal aberrations and phenotype
      effect indicates the importance of chromosome karyotyping in patients with
      abnormal reproductive history.

PMID- 15843346
TI  - [A family history of congenital fibrosis of the extraocular muscle with autosomal
      dominant inheritance].
AB  - To discover novel disease genes, a family with congenital fibrosis of the
      extraocular muscle was studied by a follow-up investigation, eye examinations and
      histo-pathological examination. There were fifteen cases suffering from
      congenital general fibrosis syndrome in four generations. They have congenital
      blepharoptosis, head tilt, chin lift, primary gaze fixed in a hypo- and exotropic
      position. The diagnosis is confirmed with positive forced duction testing in the
      affected eye. Furthermore, fibrosis of the extraocular muscles and hyaline
      degeneration was confirmed by histo-pathological examination. Except for
      different levels of restriction of the eyeball movements, other eye symptoms in
      positive patients are substantially identical. The genetic analysis showed that
      this disease was caused by autosomal dominant inheritance. The pedigree may be
      precious resource candidate for discovering disease gene related with congenital
      fibrosis of the extraocular muscle.

PMID- 15843347
TI  - [Polymorphisms and bioinformatics analysis of chicken prolactin gene].
AB  - Four chicken breeds (White Leghorn, Yangshan, Taihe Silkies, White Recessive
      Rocks) with different reproduction were applied to screen potential SNPs related
      to laying performance in the 5' flanking region, exon region and partial intron
      region of chicken prolactin (cPRL) gene. Totally almost 4500 bp were screened
      rapidly based on DNA pooling and sequencing, and thirteen single nucleotide
      polymorphisms (SNPs) and two indels (24 bp and 15 bp) were found, including nine
      SNPs and two indels in the 5' flanking region, one SNP in Exon 2, two SNPs in
      Exon 5 and one SNP in Intron 2 respectively. Furthermore, 5' flanking region of
      cPRL gene was analyzed by the website of http://motif.genome.ad.jp/. A possible
      Evi-1 binding site (score 93) was found in White Leghorn cPRL gene because of the
      24 bp insertion, another possible C/EBPbeta binding site (score 94) was found in
      Yangshan cPRL gene because of the variation of C-2402T. Further studies need to
      be carried out to verify their effects on the expression of cPRL gene, the
      broodiness and laying performance of chickens.

PMID- 15843348
TI  - [High level secretion expression of PoIFNalpha in Pichia pastoris].
AB  - The porcine alpha interferon gene was inserted into the Pichia pastoris
      expression vector of pPICZalphaA which contains AOX I promoter and alpha-factor
      signal sequence. The recombinant plasmid was transformed into host cell E.coli
      JM109 and then was extracted for analysis of restriction enzymes. It was
      confirmed that heterogeneous gene spliced into vector pPICZalphaA was IFNalpha
      gene. The recombinant plasmid of pPICZalphaA-IFNalpha was linearnized by Sac I
      and transformed into KM71 by electroporation. SDS-PAGE and Western blot analysis
      showed that IFNalpha product was observed in the supernants with a little larger
      molecular weight size than the natural IFNalpha. The rIFN gene has the same
      antigenicity as natural one. The expressed rIFN accumulated up to about
      0.45mg/mL. The cytokine activity of the supernantants was vertified by WISH/VSV
      system,which is about 2.1x10(4)IU/mL.

PMID- 15843349
TI  - Study on the chromosomal karyotype and G-banding of Alpacas (Lama pacos).
AB  - Blood samples from 23 Huacaya alpacas, 3 males and 20 females, were used to study
      chromosomes and karyotypes, so as to provide some effective cytogenetic bases for
      the selection, improvement by crossing, disease diagnosis of alpacas, and genetic
      mechanisms of sex determination. Peripheral blood lymphocyte culture was used to
      prepare chromosome. A method of trypase-EDTA was used for G-banding. The results
      showed as follows: The number of diploid chromosomes was 2n=74, with the
      karyotype 74, XY and 74, XX for males and females respectively. Thirty-six
      homologous pairs of chromosomes were autosomes, in which chromosomes pairs No.1
      to No.20 were acrocentric-subterminal and No.21 to No.36 metacentric
      submetacentric. And X chromosome was metacentric, Y chromosome telocentric. The
      analysis of G-bands showed that bright and dark bands appeared by turn. It showed
      different bands. And every pair of chromosomes had its distinct band, and the
      longer the chromosomes, the more the number of bands, and the more clear the
      bands.

PMID- 15843350
TI  - [Ribosomal protein genes highly expressed in swamp eel gonads].
AB  - 8 cDNA clones have been isolated from a cDNA library prepared from swamp eel
      testies by macroarray. DNA sequence analysis and database search showed that they
      encode 8 proteins which are highly homologous to 40S ribosomal proteins
      S4,S9,S16,S17,S20 and 60S riobosomal proteins L7, L18a,L29. Phylogenetic trees
      (ML) based on ribosomal protein genes from swamp eel and other organisms has been
      reconstructed, which showed that ribosomal protein genes were highly conserved
      during evolution. These results suggested that ribosomal protein genes as house
      keeping genes may play roles in developmental regulation such as sexual
      differentiation and can also be used as markers for the study of molecular
      evolution.

PMID- 15843351
TI  - [Molecular cloning of activin betaA subunit mature peptide from peafowl and its
      application in taxonomy and phylogeny].
AB  - The sequences of activin gene betaA subunit mature peptide have been amplified
      from white peafowl, blue peafowl (pavo cristatus) and green peafowl (pavo
      muticus) genomic DNA by polymerase chain reaction (PCR) with a pair of degenerate
      primers. The target fragments were cloned into the vector pMD18-T and sequenced.
      The length of activin gene betaA subunit mature peptide is 345bp, which encoded a
      peptide of 115 amino acid residues. Sequence analysis of activin gene betaA
      subunit mature peptide demonstrated that the identity of nucleotide is 98.0%
      between blue peaflowl and green peafowl, and the identity of that is 98.8%
      between blue peaflowl and white peafow. Sequences comparison in NCBI revealed
      that the sequences of activin gene betaA subunit mature peptides of different
      species are highly conserved during evolution process. In addition, the
      restriction enzyme map of activins is high similar between white peafowl and blue
      peafowl. Phylogenetic tree was constructed with Mega 2 and Clustalxldx software.
      The result showed that white peafowl has a closer relationship to blue peafowl
      than to green peafowl. Considered the nucleotide differences of peafowls' activin
      gene betaA subunit mature peptides, a highly conserved region, we supported that
      white peafowl was derived from blue peafowl, and it is more possible the hybrid
      but just the product of color mutation, or maybe as a subspecies of Pavo genus.

PMID- 15843352
TI  - [Identification of PCR markers associated with cytoplasmic male sterility in
      Brassica oleracea var Botrytis].
AB  - The homology-based candidate gene method was used to identified the specific PCR
      markers linked to cytoplasmic male sterility (CMS) in cauliflower( Brassica
      oleracea var botrytis.). Searching the DNA and protein data-base of NCBI ,
      correlative genes or open reading frames were identified . Analysis of biosoft,
      based on the conservative regions ,five primers were designed . Among them, only
      primer P9/P10 produced a 313- bp specific fragment. Identified by individual
      plant testing , analysis of RT-PCR and dot blot ,this fragment was only existed
      in CMS cauliflower knxd612. Analysis of the sequence indicated it was high
      homologous(98%) with orf138 of Ogura CMS radish. Primary result suggested that
      the cytoplasmic type of CMS cauliflower knxd612 may belong to Ogura type. This
      research offered a good foundation to further investigate the CMS mechanism of
      cauliflower in molecular level.

PMID- 15843353
TI  - [Expressions of LEAFY homologous genes in different organs and stages of Ginkgo
      biloba].
AB  - Expressions of Ginlfy and GinNdly gene were studied by northern blotting in
      different organs and stages of Ginkgo Biloba. Ginlfy gene was expressed in
      different organs such as root, stem, leaf of juvenile tree, male tree and female
      tree, and in different stages of male flower bud and female flower bud. It was
      inferred that Ginlfy gene could be expressed constitutionally. GinNdly gene was
      only expressed in leaf of juvenile tree, male tree and female tree and in
      different stages of male flower bud and female flower bud, while GinNdly gene was
      not expressed in the other organs. Therefore it was thought that GinNdly gene
      could be expressed differentially and be a close relation to development of
      flower.

PMID- 15843354
TI  - [Cloning and structure analysis of zinc finger protein gene in Populus euphratica
      Oliv].
AB  - Zinc finger proteins belong to a family of nuclear transcription factors which
      function is to regulate gene expression in both prokaryotic and eukaryotic cells.
      A pair of primers was designed after analyzing the conservation of salt-tolerant
      zinc protein Alfin-1 in such diverse plants as alfalfa and Arabidopsis. The zinc
      finger protein gene is isolated from total RNA with RT-PCR in aquaculture leaves
      of Populus euphratica . Its full cDNA length is 924bp. Analysis of its amino acid
      sequence showed it has a typical Cys(2)/His(2) zinc finger structure and a G-rich
      promoter binding site GTGGGG, starting from position 556. Since transcrptional
      factors which have the same function show conservation in structure and amino
      acid sequence of DNA binding region, the structure analysis in this paper
      indicates the cloned zinc finger protein gene may have functional correlation to
      Alfin-1.

PMID- 15843355
TI  - [Anti-oxidative effect of ribonuclease inhibitor by site-directed mutagenesis and
      expression in Pichia pastoris].
AB  - Human placental ribonuclease inhibitor is an acidic protein of Mr approximately
      50 kDa with unusually high contents of leucine and cysteine. It is a cytosolic
      protein that protects cells from the adventitious invasion of pancreatic-type
      ribonuclease. HRI has 32 cysteine residues, and the oxidative formation of
      disulfide bonds from those cysteine residues is a rapid cooperative process that
      inactivates HRI. The most proximal cysteine residues in native HRI are two pairs
      that are adjacent in sequence. In the present paper, two molecules of alanine to
      substitute for cys328/cys329 were performed by site-directed mutagenesis. The
      site-mutated RI cDNA was constructed into plasmid pPIC9K, and then transformed
      Pichia pastoris GS115 by electroporation. After colony screening , the bacterium
      was cultured and the product was purified with affinity chromatography. The
      affinity of the recombinant human RI with double site mutation was examined for
      RNase A and its anti-oxidative effect. The results indicated that there was no
      much change in the affinity for RNase A detected when compared with the wild type
      of RI. But the capacity of anti-oxidative effect was increased by 7-9 times. The
      enhance in anti-oxidative effect might be the reason for preventing the formation
      of disulfide bond between cys328 and cys329 and the three dimensional structure
      of RI was thereby maintained.

PMID- 15843356
TI  - [Differences of gene expression in bud stage of backcross hybrid between Ogura
      type male-sterile Brassica napus L and B campestris L versus parents].
AB  - Crosses between female parent of Ogura male sterility Brassica napus L. and male
      parents of B. campestris ssp. chinensis Makino were made and F(1), BC(1) and
      BC(2) generations produced. Gene expression of two Chinese cabbage backcross
      hybrid BC(1), BC(2) and their parents at bud stage was analyzed by means of cDNA
      AFLP technique. The results indicated that the patterns of gene expression differ
      significantly between BC(1) and BC(2) generations and their parents. There were
      many patterns of gene expression, including gene overexpression and gene
      silencing. Five patterns (seven kinds) of gene expression were observed, which
      include: (1) bands occurring in only one parent (two kinds); (2) bands observed
      in hybrids and one parent (two kinds); (3) bands occurring in only parents (one
      kind); (4) bands visualized in only hybrids (one kind); (5) bands observed in
      parents and hybrids (one kind). In accompany with the addition of backcross, the
      increase trend in backcross hybrids and their parents were described in the
      aspects of differential gene expression, bands expressed only in one parent and
      bands expressed only in both parents. The declined trend in backcross hybrids and
      their parents were observed in the aspects of bands expressed in both hybrids and
      one parent (two kinds), bands visualized in only hybrids and bands observed in
      parents and hybrid. Fifteen patterns of gene expression were observed in
      F(1)bBC(1)bBC(2) and backcross parents. The percent of bands expressed in
      F(1)bBC(1)bBC(2) and backcross was highest.

PMID- 15843357
TI  - [Search engine of genetics journals from Medline (PubMed)].
AB  - To help geneticists look up genetics journals more quickly and exactly,this paper
      developed this search engine of genetics journals. The paper exploited the search
      engine with genetics journals sources of Medline database in NCBI, indexed and
      listed 173 names of genetics journals from Medline. Then obtained one search
      engine concerning genetics journals after making every journal's super linkage.
      The search engine can search out not only all articles' titles of 173 genetics
      journals but also some articles' titles of the journals each year quickly,
      exactly and dynamically. We can further obtain all articles' abstracts and some
      full texts in PubMed.

PMID- 15843358
TI  - [The detection of plasmid pCAMBIA1301 in transgenic rice by arrayed primer
      extension].
AB  - Biochip technology which had emerged from the fusion of biotechnology and
      micro/nanofabrication technology at the end of 1980s has been widely used in life
      science, medicine, clinical diagnosis, drug development, agriculture,
      environmental protection and strategies. DNA microarray (also call gene chip, DNA
      chip), one kind of biochips, is small chip containing many oligonucleotide
      probes. It can hybridize with labelled sample, making it possible to detect large
      numbers of oligonucleotides at one time. So DNA microarray can overcome the
      disadvantage of traditional hybridization technology such as complexity, low
      automation, poor efficiency and quantity of molecules detected. This paper
      describes a new method to detect transgenic plant with gene chip. We have
      developed a novel arrayed-primer extension technique. It combines hybridization
      and PCR in one step, while ordinary DNA microarray needs two separate steps.
      Therefore our method provide a feasibility to detect long DNA fragment .

PMID- 15843359
TI  - [Novel mechanism of 3' exonuclease of polymerase in maintenance of DNA
      replication fidelity and its application in SNP assay].
AB  - Polymerase with 3' to 5'exonulcease plays an important role in the maintenance of
      in vivo DNA replication fidelity. In order to develop more reliable SNP assays,
      we revisit the underlying molecular mechanisms by which DNA polymerases with 3'
      exonucleases maintain high fidelity of DNA replication. In addition to mismatch
      removal by proofreading, we recently discovered a premature termination of
      polymerization by a new mechanism of OFF-switch. This novel ON/OFF switch turns
      off DNA polymerization from mismatched primers and turns on DNA polymerization
      from matched primers. Two SNP assays were developed based on the proofreading and
      the newly identified OFF-switch respectively: terminal labeled primer extension
      and the ON/OFF switch operated SNP assay. These two new methods are well adapted
      to conventional techniques such as electrophoresis, real time PCR, microplates,
      and microarray. Application of these reliable SNP assays will greatly facilitate
      genetic and biomedical studies in the post-genome era.

PMID- 15843360
TI  - [Alu family and its biological significance].
AB  - The Alu family of short (approximately 300bp)interspersed elements (SINEs) is one
      of the most successful mobile genetic elements, having arisen to a copy number in
      excess of 500,000 within primate genomes in the last 65 million years. The
      proliferation of these elements had a significant impact on the architecture of
      primate genomes. Now the functions of Alu elements are still unclear. It is
      speculated that Alu elements are involved in aspects of gene regulation, e.g.
      gene rearrangement, CpG methylation, alternative splicing of hnRNA, binding sites
      of transcription factors and hormone receptors, etc. At the same time, Alu family
      is an important research method in human population genetics, forensic, oncology,
      etc. Additionally, Alu insertion, deletion and recombination led to many ancestor
      genetic diseases and cancers.

PMID- 15843361
TI  - [Nuclear transfer and therapeutic cloning].
AB  - Nuclear transfer and therapeutic cloning have widespread and attractive prospects
      in animal agriculture and biomedical applications. We reviewed that the quality
      of oocytes and nuclear reprogramming of somatic donor cells were the main reasons
      of the common abnormalities in cloned animals and the low efficiency of cloning
      and showed the problems and outlets in therapeutic cloning, such as some basic
      problems in nuclear transfer affected clinical applications of therapeutic
      cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES)
      cells and specific differentiation of ntES cells into important functional cells
      should be emphasized and could enhance the efficiency. Adult stem cells could
      help to cure some great diseases, but could not replace therapeutic cloning.
      Ethics also impeded the development of therapeutic cloning. It is necessary to
      improve many techniques and reinforce the research of some basic theories, then
      somatic nuclear transfer and therapeutic cloning may apply to agriculture
      reproduction and benefit to human life better.

PMID- 15843362
TI  - [Progress in the investigation of Avian sex determination and sex
      identification].
AB  - Avian sex determination is a multiple gene regulation cascade. Genes such as the
      Z chromosome-linked DMRT1 gene, W chromosome-linked PKCIW gene and other factors
      have been demonstrated to be involved in this process. In this paper, we review
      the recent progress in this field. The investigation of functions of sex
      determinate genes and methods of sexing identification in birds are also
      discussed.

PMID- 15843363
TI  - [Progress in the molecular mechanisms of nuclear coactivator PGC-1].
AB  - Peroxisome proliferators-activated receptor-gamma coactivator-1 is broadly
      involved in several key cellular pathways including mitochondrial biogenesis,
      hepatic gluconeogenesis via interacting with many transcription factors, which is
      highly valuable to maintain the energy balance of organisms. This review
      especially focuses on the recent progress in the molecular docking, histone
      acetylation, RNA processing basing on the structure of PGC-1 gene and amino acid
      sequence. Besides, the prospect of PGC-1 in applications of metabolic syndromes
      has been discussed also.

PMID- 15843364
TI  - [Differential display technique and its progress].
AB  - Differential display technique is an important method to isolate differentially
      expressed gene. Comparing to other methods like representational difference
      analysis, suppression subtractive hybridization and serial analysis of gene
      expression, differential display technique is used in higher frequency. Since it
      was established in 1992, it has overcome many disadvantages and widened its
      practical fields through improvements and enhancements by global researchers. In
      this paper the principle and the main advantages and disadvantages of
      differential display technique were briefly introduced. Meanwhile, the four
      progressed aspects in designing primer, reducing false positives, identifying
      differentially expressed gene and techniques derived from DD were introduced in
      detail.

PMID- 15843365
TI  - [Chromosomal behaviors in plant wide hybridizations and their genetic and
      evolutionary implications].
AB  - The wide hybridization and polyploidization play a significant role in the
      evolution of higher plants. On the contrary, the artificially synthesized
      allopolyploids are genetically unstable and fail to be used as crops. One reason
      for this situation may be that the allopolyploids in nature are the products of
      natural selection and evolution and it is difficult for human to repeat and
      perform the process in short periods. Another reason is that we know little about
      the interaction mechanisms between the genomes of different origins. So the
      genetics and epigenetics after allopolyploidizations are now studied by
      multidisciplinary approaches. The spatial separation of parental genomes in
      hybrid cells have been observed in some sexual and somatic hybrids, but the
      biological meanings remain to clarify. The abnormal chromosome behaviors in plant
      wide crosses, such as pseudogamy, semigamy, chromosome elimination and the
      mitotic and meiotic separation of parental genomes, may indicate the
      incompatibility of two parental species at gametic and chromosomal levels. The
      systematic studies at different levels on chromosomal behavior and genetics in
      plant hybridizations are needed to undermine the mechanisms responsible for the
      formation and evolution of new species.

PMID- 15843366
TI  - [Advances in cryptocromes and their signal transduction].
AB  - Cryptochromes are blue light receptors which share the similar function with the
      phytochromes in regulation of the growth and development in plants. After 90's,
      especially in the recent years, profound studies have been carried around the
      cryptochromes. Cryptochromes were found not only in plants, but also in animals.
      It has been known that cryptochromes are involved in de-etiolation in seed
      germination, photoperiodic-inductive flowering, regulation of circadian rhythm,
      etc. In the article, we introduced the characteristics of cryptochromes and the
      genes, including cryptochromes structure, the presence in plant kingdom, the
      localization in cells, and the expression regulated by light. In addition, the
      function of cryptochrome in plant photomorphogenesis and in controlling of the
      circadian clock in plants and animals was summarized. Through analysis of the
      relationships between cryptochromes and the interacted proteins, we clarified
      primarily the roles of how cryptochromes mediate the plant growth and development
      via interacting with proteins in the signal pathway. It was suggested that
      studying the cryptochromes and their signal transduction profoundly to disclose
      the nature of plant photomorphogenesis will be of great importance both to
      biologic theory as well as application.

PMID- 15843367
TI  - [Epigenetic phenomena of plant polyploids].
AB  - Epigenetic phenomena, heritable changes in phenotype, and hence in gene
      regulation, but not in DNA sequence, occur in the process of polyploidization in
      many plants. These phenomena include gene silencing, DNA methylation, nucleolar
      dominance, transposable elements activation and genomic imprinting. Epigenetic
      phenomena might be caused by gene silencing or alternative gene expression from
      intergenomic interaction. These could also be induced from the changes of histone
      coding, without DNA methylation. Furthermore, hypomethylation, chromatin
      reconstitution or transposable element activation could contribute to epigenetic
      phenomena. These modifications may give rise to the diversification of gene
      expressing, to the genetic and cytological diploidization, as well as to
      intergenomic coordination. This paper reviews epigenetic phenomena in many plants
      and their influence on evolution of plant genome, thus hint the likely pathway of
      research in this field.

PMID- 15843368
TI  - Plasmodium vivax malaria presenting with severe thrombocytopenia.
AB  - Haematological changes are common in malaria. Thrombocytopenia is a common
      finding in falciparum infection but rare in Plasmodium vivax. We report a case of
      7-year-old male patient presenting with fever, petechial rash, and platelet
      counts of 6 x 10(9)/l due to Plasmodium vivax malaria.

PMID- 15843369
TI  - Potential cytoplasmic inheritance in Wisteria sinensis and Robinia pseudoacacia
      (Leguminosae).
AB  - We examined pollen cells of Wisteria sinensis and Robinia pseudoacacia
      (Leguminosae) to determine a possible mode for cytoplasmic inheritance in these
      species. Epifluorescence microscopy revealed distinct mature generative cells.
      Mature generative cells of W. sinensis were associated with large numbers of
      punctuated fluorescent signals corresponding to cytoplasmic DNA aggregates, but
      no fluorescent signals were observed in the generative cells of R. pseudoacacia.
      Closer examination showed that the punctate fluorescent signals corresponded to
      plastid but not mitochondrial DNA. These results suggest a strong potential for
      paternal transmission of the plastid genome in W. sinensis. Electron microscopy
      confirmed the presence of plastids in the generative cells of W. sinensis and the
      absence of plastids in R. pseudoacacia cells due to an unequal distribution of
      plastids during the first pollen mitosis. Mitochondria were present and intact in
      the mature generative cells of both species. The lack of fluoresced mitochondrial
      DNA suggests a very low level of mitochondrial DNA in the cells. Immunoelectron
      microscopy demonstrated that the labeling of mitochondrial DNA in these cells was
      reduced by nearly 90% during pollen development. Such a dramatic reduction
      suggests an active degradation of paternal mitochondrial DNA, which may
      contribute greatly to the maternal inheritance of mitochondria. In short, we
      found that W. sinensis exhibits a strong potential for paternal transmission of
      plastids and that both W. sinensis and R. pseudoacacia appear to share the same
      mechanism for maternal mitochondrial inheritance.

PMID- 15843370
TI  - The adipocyte as an important target cell for Trypanosoma cruzi infection.
AB  - Adipose tissue plays an active role in normal metabolic homeostasis as well as in
      the development of human disease. Beyond its obvious role as a depot for
      triglycerides, adipose tissue controls energy expenditure through secretion of
      several factors. Little attention has been given to the role of adipocytes in the
      pathogenesis of Chagas disease and the associated metabolic alterations. Our
      previous studies have indicated that hyperglycemia significantly increases
      parasitemia and mortality in mice infected with Trypanosoma cruzi. We determined
      the consequences of adipocyte infection in vitro and in vivo. Cultured 3T3-L1
      adipocytes can be infected with high efficiency. Electron micrographs of infected
      cells revealed a large number of intracellular parasites that cluster around
      lipid droplets. Furthermore, infected adipocytes exhibited changes in expression
      levels of a number of different adipocyte-specific or adipocyte-enriched
      proteins. The adipocyte is therefore an important target cell during acute Chagas
      disease. Infection of adipocytes by T. cruzi profoundly influences the pattern of
      adipokines. During chronic infection, adipocytes may represent an important long
      term reservoir for parasites from which relapse of infection can occur. We have
      demonstrated that acute infection has a unique metabolic profile with a high
      degree of local inflammation in adipose tissue, hypoadiponectinemia,
      hypoglycemia, and hypoinsulinemia but with relatively normal glucose disposal
      during an oral glucose tolerance test.

PMID- 15843371
TI  - Cellular fibronectin binds to lysyl oxidase with high affinity and is critical
      for its proteolytic activation.
AB  - Lysyl oxidase (LOX) is a copper-containing amine oxidase known to catalyze the
      covalent cross-linking of fibrillar collagens and elastin at peptidyl lysine
      residues. In addition, its involvement in cancer, wound healing, cell motility,
      chemotaxis, and differentiation reflect a remarkable functional diversity of LOX.
      To investigate novel mechanisms of LOX regulation and function, we performed a
      yeast two-hybrid screen to identify LOX-interacting proteins. Three overlapping
      positive clones were identified as C-terminal fragments of fibronectin (FN).
      Glutathione S-transferase pull-downs and solid phase binding assays confirmed
      this interaction. LOX binds to the cellular form of FN (cFN) with a dissociation
      constant (K(d)) of 2.5 nm. This was comparable with our measured K(d) of LOX
      binding to tropoelastin (1.9 nm) and type I collagen (5.2 nm), but LOX
      demonstrated a much lower binding affinity for the plasma form of FN (pFN).
      Immunofluorescent microscopy revealed co-localization of FN and LOX in normal
      human tissues, where these proteins may interact in vivo. LOX enzymatic activity
      assays showed that cFN does not seem to be a substrate of LOX. However, cFN can
      act as a scaffold for enzymatically active 30-kDa LOX. Furthermore, in FN-null
      mouse embryonic fibroblasts, we observed dramatically decreased proteolytic
      processing of the 45-kDa LOX proenzyme to the 30-kDa active form, with a
      corresponding decrease in LOX enzyme activity. Our results suggest that the FN
      matrix may provide specific microenvironments to regulate LOX catalytic activity.

PMID- 15843372
TI  - Extracellular matrix remodeling by human granzyme B via cleavage of vitronectin,
      fibronectin, and laminin.
AB  - Human granzyme B (GrB) released from cytotoxic lymphocytes plays a key role in
      the induction of target cell apoptosis when internalized in the presence of
      perforin. Here we demonstrate that GrB also possesses a potent extracellular
      matrix remodeling activity. Both native and recombinant GrB caused detachment of
      immortalized and transformed cell lines, primary endothelial cells, and
      chondrocytes. Cell detachment by GrB induced endothelial cell death (anoikis).
      GrB also inhibited tumor cell spreading, migration, and invasion in vitro.
      Investigation into the underlying mechanism revealed that GrB efficiently cleaves
      three proteins involved in extracellular matrix structure and function:
      vitronectin, fibronectin, and laminin. In vitronectin, GrB cleaves after an Arg
      Lys-Asp (RGD) motif, which is part of the integrin-binding site found in matrix
      proteins. We propose that targeting of the integrin-extracellular matrix
      interface by GrB may allow perforin-independent killing of target cells via
      anoikis, restrict motility of tumor cells, facilitate lymphocyte migration, or
      directly reduce virus infectivity. It may also contribute to tissue destruction
      in diseases in which extracellular GrB is evident, such as rheumatoid arthritis
      and atherosclerosis.

PMID- 15843373
TI  - Natural antisense mRNAs to hyaluronan synthase 2 inhibit hyaluronan biosynthesis
      and cell proliferation.
AB  - We report the identification of a natural antisense mRNA of hyaluronan synthase 2
      that we have chosen to designate as HASNT (for HA synthase 2 antisense) in human
      and mouse. HASNT is transcribed from the opposite strand of the HAS2 gene locus
      and is represented by several independent expressed sequence tags in human.
      Portions of the mouse Hasnt gene were identified through an exon-trapping
      approach. Sequence conservation is extremely low between human and mouse HASNT,
      and it is not clear whether these mRNAs contain functional open reading frames.
      HASNT has an alternate splice site in both human and mouse. This splice site is
      located at an identical position within the gene in both species and results in
      mRNAs of two different lengths. In each species, the antisense portion of the
      HASNT gene is complementary to the first exon of HAS2, which represents the 5'
      untranslated region. To study the biological activity of HASNT, two human
      expressed sequence tag clones, representing long and short HASNT splice variants,
      were cloned into a tetracycline-inducible vector and were stably transfected into
      human osteosarcoma U2-OS Tet-on cells. The long and short HASNT-expressing cells
      had a reduction in HAS2 mRNA levels up to 94 and 86%, respectively, whereas
      hyaluronan biosynthesis was inhibited by 40 and 37%, respectively. Cell
      proliferation was reduced throughout the time frame of the experiment. Exogenous
      high molecular mass hyaluronan failed to rescue the suppressed cell
      proliferation, whereas adenoviral-mediated overexpression of hyaluronan synthase
      3, which stimulated endogenous hyaluronan biosynthesis, was able to rescue.
      Collectively, our data suggest that natural antisense mRNAs of HAS2 are able to
      regulate HAS2 mRNA levels and hyaluronan biosynthesis in a cell culture model
      system and may have an important and novel regulatory role in the control of
      HAS2, HA biosynthesis, and HA-dependent cell functions in vivo.

PMID- 15843374
TI  - Application of the "codon-shuffling" method. Synthesis and selection of de novo
      proteins as antibacterials.
AB  - Library-based methods of non-rational and part-rational designed de novo peptides
      are worthy beacons in the search for bioactive peptides and proteins of medicinal
      importance. In this report, we have used a recently developed directed evolution
      method called "codon shuffling" for the synthesis and selection of bioactive
      proteins. The selection of such proteins was based on the creation of an
      inducible library of "codon-shuffled" genes that are constructed from the
      ligation-based assembly of judiciously designed hexamer DNA duplexes called
      dicodons. Upon induction with isopropyl 1-thio-beta-D-galactopyranoside, some
      library members were found to express dicodon-incorporated proteins. Because of
      this, the host cells, in our case Escherichia coli, were unable to grow any
      further. The bactereostatic/lytic nature of the dicodon proteins was monitored by
      growth curves as well as by zone clearance studies. Transmission electron
      microscopy of the affected cells illustrated the extent of cell damage. The
      proteins themselves were overexpressed as fusion partners and subsequently
      purified to homogeneity. One such purified protein was found to strongly bind
      heparin, an indication that the interaction of the de novo proteins may be with
      the nucleic acids of the host cell, much like many of the naturally occurring
      antibacterial peptides, e.g. Buforin. Therefore, our approach may help in
      generating a multitude of finely tuned antibacterial proteins that can
      potentially be regarded as lead compounds once the method is extended to
      pathogenic hosts, such as Mycobacteria, for example.

PMID- 15843375
TI  - Disassembling protein aggregates in the yeast cytosol. The cooperation of Hsp26
      with Ssa1 and Hsp104.
AB  - In all organisms studied, elevated temperatures induce the expression of a
      variety of stress proteins, among them small Hsps (sHsp). sHsps are chaperones
      that prevent the unspecific aggregation of proteins by forming stable complexes
      with unfolded polypeptides. Reactivation of captured proteins requires the
      assistance of other ATP-dependent chaperones. How sHsps and ATP-dependent
      chaperones work together is poorly understood. Here, we analyzed the interplay of
      chaperones present in the cytosol of Saccharomyces cerevisiae. Specifically, we
      characterized the influence of Hsp104 and Ssa1 on the disassembly of Hsp26 x
      substrate complexes in vitro and in vivo. We show that recovery of proteins from
      aggregates in the cell requires the chaperones to work together with defined but
      overlapping functions. During reactivation, proteins are transferred from a
      stable complex with Hsp26 to Hsp104 and Hsp70. The need for ATP-dependent
      chaperones depends on the type of sHsp x substrate complex. Although Ssa1 is able
      to release substrate proteins from soluble Hsp26 x substrate complexes, Hsp104 is
      essential to dissociate substrate proteins from aggregates with incorporated
      sHsps. Our results are consistent with a model of several interrelated defense
      lines against protein aggregation.

PMID- 15843376
TI  - Identification of Trichomonas vaginalis cysteine proteases that induce apoptosis
      in human vaginal epithelial cells.
AB  - A secreted cysteine protease (CP) fraction from Trichomonas vaginalis is shown
      here to induce apoptosis in human vaginal epithelial cells (HVEC) and is analyzed
      by mass spectrometry. The trichomonad parasite T. vaginalis causes one of the
      most common non-viral sexually transmitted infection in humans, trichomoniasis.
      The parasite as well as a secreted cysteine protease (CP) fraction, isolated by
      affinity chromatography followed by Bio-Gel P-60 column chromatography, are shown
      to induce HVEC apoptosis, as demonstrated by the Cell Death Detection ELISA(PLUS)
      assay and annexin V-fluorescein isothiocyanate flow cytometry analyses.
      Initiation of apoptosis is correlated with protease activity because the specific
      CP inhibitor E-64 inhibits both activities. SDS-PAGE analysis of the CP fraction
      reveals triplet bands around 30 kDa, and matrix-assisted laser desorption
      ionization time-of-flight MS indicates two closely associated peaks of molecular
      mass 23.6 and 23.8 kDa. Mass spectral peptide sequencing of the proteolytically
      digested CPs results in matches to previously reported cDNA clones, CP2, CP3, and
      CP4 (Mallinson, D. J., Lockwood, B. C., Coombs, G. H., and North, M. J. (1994)
      Microbiology 140, 2725-2735), as well as another sequence with high homology to
      CP4 (www.tigr.org). These last two species are the most abundant components of
      the CP fraction. The present results, suggesting that CP-induced programmed cell
      death may be involved in the pathogenesis of T. vaginalis infection in vivo, may
      have important implications for therapeutic intervention.

PMID- 15843377
TI  - Phosphorylation of human p53 at serine 46 determines promoter selection and
      whether apoptosis is attenuated or amplified.
AB  - The capacity of DNA damaging agents to induce apoptosis is regulated by target
      gene induction by p53. We found that p53 targeted MDM2 in cells in which DNA
      repair was occurring, but persistent DNA damage induced by chemotherapy led p53
      to selectively target PTEN. High dose chemotherapy induced the phosphorylation of
      p53 on serine 46, whereas low dose chemotherapy did not. A nonphosphorylatable
      serine 46 to alanine p53 mutant (S46A) targeted the MDM2 promoter in preference
      to that for PTEN. A serine 46 to aspartate mutant (S46D, a phosphorylation mimic)
      targeted PTEN in preference to MDM2. These observations show that phosphorylation
      of serine 46 in p53 is sufficient for it to induce the PTEN (phosphatase and
      tensin homolog deleted on chromosome ten) tumor suppressor protein in preference
      to MDM2. S46A induced significantly less cell death than the S46D in cells. The
      phosphorylation-induced change of p53 promoter targeting suppresses the induction
      of MDM2 and the formation of the autoregulatory feedback loop. Induction of PTEN
      by p53 followed by expression of PTEN inhibits AKT-induced translocation of MDM2
      into the nucleus and sustains p53 function. The protection of p53 from MDM2 by
      PTEN and the damage-induced activation of PTEN by phosphorylated p53 leads to the
      formation of an apoptotic amplification cycle in which p53 and PTEN coordinately
      increase cellular apoptosis.

PMID- 15843378
TI  - Candida albicans Pmr1p, a secretory pathway P-type Ca2+/Mn2+-ATPase, is required
      for glycosylation and virulence.
AB  - The cell surface of Candida albicans is the immediate point of contact with the
      host. The outer layer of the cell wall is enriched in highly glycosylated
      mannoproteins that are implicated in many aspects of the host-fungus interaction.
      Glycosylation of cell wall proteins is initiated in the endoplasmic reticulum and
      then elaborated in the Golgi as the protein passes through the secretory pathway.
      Golgi-bound mannosyltransferases require Mn(2+) as an essential cofactor. In
      Saccharomyces cerevisiae, the P-type ATPase Pmr1p transports Ca(2+) and Mn(2+)
      ions into the Golgi. To determine the effect of a gross defect in glycosylation
      on host-fungus interactions of C. albicans, we disrupted the PMR1 homolog,
      CaPMR1. This mutation would simultaneously inhibit many Golgi-located, Mn(2+)
      dependent mannosyltransferases. The Capmr1Delta null mutant was viable in vitro
      and had no growth defect even on media containing low Ca(2+)/Mn(2+) ion
      concentrations. However, cells grown in these media progressively lost viability
      upon entering stationary phase. Phosphomannan was almost completely absent, and O
      mannan was severely truncated in the null mutant. A defect in N-linked outer
      chain glycosylation was also apparent, demonstrated by the underglycosylation of
      surface acid phosphatase. Consistent with the glycosylation defect, the null
      mutant had a weakened cell wall, exemplified by hypersensitivity to Calcofluor
      white, Congo red, and hygromycin B and constitutive activation of the cell
      integrity pathway. In a murine model of systemic infection, the null mutant was
      severely attenuated in virulence. These results demonstrate the importance of
      glycosylation for cell wall structure and virulence of C. albicans.

PMID- 15843379
TI  - A non-sulfated form of the HNK-1 carbohydrate is expressed in mouse kidney.
AB  - The HNK-1 carbohydrate, which is recognized by anti-HNK-1 antibody, is well known
      to be expressed predominantly in the nervous system. The characteristic
      structural feature of the HNK-1 carbohydrate is 3-sulfo-glucuronyl residues
      attached to lactosamine structures (Gal beta1-4GlcNAc) on glycoproteins and
      glycolipids. The biosynthesis of the HNK-1 carbohydrate is regulated mainly by
      two glucuronyltransferases (GlcAT-P and GlcAT-S) and a sulfotransferase. In this
      study, we found that GlcAT-S mRNA was expressed at higher levels in the kidney
      than in the brain, but that both GlcAT-P and HNK-1 sulfotransferase mRNAs, which
      were expressed at high levels in the brain, were not detected in the kidney.
      These results suggested that the HNK-1 carbohydrate without sulfate (non-sulfated
      HNK-1 carbohydrate) is expressed in the kidney. We substantiated this hypothesis
      using two different monoclonal antibodies: one (anti-HNK-1 antibody) requires
      sulfate on glucuronyl residues for its binding, and the other (antibody M6749)
      does not. Western blot analyses of mouse kidney revealed that two major bands (80
      and 140 kDa) were detected with antibody M6749, but not with anti-HNK-1 antibody.
      The 80- and 140-kDa band materials were identified as meprin alpha and
      CD13/aminopeptidase N, respectively. We also confirmed the presence of the non
      sulfated HNK-1 carbohydrate on N-linked oligosaccharides by multistage tandem
      mass spectrometry. Immunofluorescence staining with antibody M6749 revealed that
      the non-sulfated HNK-1 carbohydrate was expressed predominantly on the apical
      membranes of the proximal tubules in the cortex and was also detected in the thin
      ascending limb in the inner medulla. This is the first study indicating the
      presence of the non-sulfated HNK-1 carbohydrate being synthesized by GlcAT-S in
      the kidney. The results presented here constitute novel knowledge concerning the
      function of the HNK-1 carbohydrate.

PMID- 15843381
TI  - ADAMTS1 proteinase is up-regulated in wounded skin and regulates migration of
      fibroblasts and endothelial cells.
AB  - The metalloproteinase ADAMTS1 (a disintegrin and metalloproteinase with
      thrombospondin motifs) is induced under inflammatory conditions, and it is also a
      potent inhibitor of angiogenesis. Due to these properties, we speculated about
      the role of ADAMTS1 in cutaneous wound repair. Here we have shown up-regulation
      of ADAMTS1 expression in wounds of normal and particularly of healing-impaired
      genetically diabetic mice. Immunofluorescence staining identified macrophages as
      the source of ADAMTS1 in early wounds, whereas keratinocytes and fibroblasts
      produce this protein at later stages of wound healing. The distribution of
      ADAMTS1 in the normal and wounded epidermis, its regulation in cultured
      keratinocytes, as well as the skin phenotype of ADAMTS1 knock-out mice suggests a
      role of this metalloproteinase in keratinocyte differentiation. Furthermore, we
      provide evidence for a novel dual function of ADAMTS1 in fibroblast migration;
      although low concentrations of this protein stimulate fibroblast migration via
      its proteolytic activity, high concentrations inhibit this process because of
      binding to fibroblast growth factor-2 and subsequent inhibition of its
      promotogenic activity. Similar effects were also observed with endothelial cells.
      Taken together, our results suggest a role of ADAMTS1 in keratinocyte
      differentiation and migration of fibroblasts and endothelial cells in healing
      skin wounds.

PMID- 15843382
TI  - Hyaluronan fragments induce endothelial cell differentiation in a CD44- and
      CXCL1/GRO1-dependent manner.
AB  - Hyaluronan is a glycosaminoglycan of the extracellular matrix. In tumors and
      during chronic inflammatory diseases, hyaluronan is degraded to smaller
      fragments, which are known to stimulate endothelial cell differentiation. In this
      study, we have compared the molecular mechanisms through which hyaluronan
      dodecasaccharides (HA12), and the known angiogenic factor, fibroblast growth
      factor 2 (FGF-2), induce capillary endothelial cell sprouting in a three
      dimensional collagen gel. The gene expression profiles of unstimulated and HA12-
      or FGF-2-stimulated endothelial cells were compared using a microarray analysis
      approach. The data revealed that both FGF-2 and HA12 promoted endothelial cell
      morphogenesis in a process depending on the expression of ornithine decarboxylase
      (Odc) and ornithine decarboxylase antizyme inhibitor (Oazi) genes. Among the
      genes selectively up-regulated in response to HA12 was the chemokine CXCL1/GRO1
      gene. The notion that the induction of CXCL1/GRO1 is of importance for HA12
      induced endothelial cell sprouting was supported by the fact that morphogenesis
      was inhibited by antibodies specifically neutralizing the CXCL1/GRO1 protein
      product. HA12-stimulated endothelial cell differentiation was exerted via binding
      to CD44 since it was inhibited by antibodies blocking CD44 function. Our data
      show that hyaluronan fragments and FGF-2 affect endothelial cell morphogenesis by
      the induction of overlapping but also by distinct sets of genes.

PMID- 15843380
TI  - Inhibiting MAP kinase activity prevents calcium transients and mitosis entry in
      early sea urchin embryos.
AB  - A transient calcium increase triggers nuclear envelope breakdown (mitosis entry)
      in sea urchin embryos. Cdk1/cyclin B kinase activation is also known to be
      required for mitosis entry. More recently, MAP kinase activity has also been
      shown to increase during mitosis. In sea urchin embryos, both kinases show a
      similar activation profile, peaking at the time of mitosis entry. We tested
      whether the activity of both kinases is required for mitosis entry and whether
      either kinase controls mitotic calcium signals. We found that reducing the
      activity of either mitotic kinase prevents nuclear envelope breakdown, despite
      the presence of a calcium transient, when cdk1/cyclin B kinase activity is alone
      inhibited. When MAP kinase activity alone was inhibited, the calcium signal was
      absent, suggesting that MAP kinase activity is required to generate the calcium
      transient that triggers nuclear envelope breakdown. However, increasing
      intracellular free calcium by microinjection of calcium buffers or InsP(3) while
      MAP kinase was inhibited did not itself induce nuclear envelope breakdown,
      indicating that additional MAP kinase-regulated events are necessary. After MAP
      kinase inhibition early in the cell cycle, the early events of the cell cycle
      (pronuclear migration/fusion and DNA synthesis) were unaffected, but chromosome
      condensation and spindle assembly are prevented. These data indicate that in sea
      urchin embryos, MAP kinase activity is part of a signaling complex alongside two
      components previously shown to be essential for entry into mitosis: the calcium
      transient and the increase in cdk1/cyclinB kinase activity.

PMID- 15843383
TI  - Identification of FEZ1 as a protein that interacts with JC virus agnoprotein and
      microtubules: role of agnoprotein-induced dissociation of FEZ1 from microtubules
      in viral propagation.
AB  - The human polyomavirus JC virus (JCV) is the causative agent of a fatal
      demyelinating disease, progressive multifocal leukoencephalopathy, and encodes
      six major proteins, including agnoprotein. Agnoprotein colocalizes with
      microtubules in JCV-infected cells, but its function is not fully understood. We
      have now identified fasciculation and elongation protein zeta 1 (FEZ1) as a
      protein that interacted with JCV agnoprotein in a yeast two-hybrid screen of a
      human brain cDNA library. An in vitro binding assay showed that agnoprotein
      interacted directly with FEZ1 and microtubules. A microtubule cosedimentation
      assay revealed that FEZ1 also associates with microtubules and that agnoprotein
      induces the dissociation of FEZ1 from microtubules. Agnoprotein inhibited the
      promotion by FEZ1 of neurite outgrowth in PC12 cells. Conversely, overexpression
      of FEZ1 suppressed JCV protein expression and intracellular trafficking in JCV
      infected cells. These results suggest that FEZ1 promotes neurite extension
      through its interaction with microtubules, and that agnoprotein facilitates JCV
      propagation by inducing the dissociation of FEZ1 from microtubules.

PMID- 15843384
TI  - Helicobacter pylori-induced macrophage apoptosis requires activation of ornithine
      decarboxylase by c-Myc.
AB  - Helicobacter pylori infection causes chronic inflammation of the gastric mucosa
      that results from an ineffective immune response. We have demonstrated that one
      underlying mechanism is induction of macrophage apoptosis mediated by polyamines.
      The transcription factor c-Myc has been linked to induction of ornithine
      decarboxylase (ODC), the rate-limiting enzyme in polyamine synthesis. We
      determined whether H. pylori stimulates transcriptional activation of ODC in
      macrophages, whether this occurs via c-Myc, and whether these events regulate
      activation of apoptosis. H. pylori induced a significant increase in ODC promoter
      activity that peaked at 6 h after stimulation and was closely paralleled by
      similar increases in ODC mRNA, protein, and enzyme activity. By 2 h after
      stimulation, c-Myc mRNA and protein expression was induced, protein was
      translocated to the nucleus, and there was specific binding of a consensus probe
      for c-Myc to nuclear extracts. Both an antennapedia-linked inhibitor of c-Myc
      binding (Int-H1-S6A,F8A) and transfection of a c-Myc dominant-negative construct
      significantly attenuated H. pylori-induced ODC promoter activity, mRNA, enzyme
      activity, and apoptosis in parallel. Transfection of ODC small interfering RNA
      inhibited ODC activity and apoptosis to the same degree as inhibition of c-Myc
      binding. These studies indicate that c-Myc is an important mediator of macrophage
      activation and may contribute to the mucosal inflammatory response to pathogens
      such as H. pylori by its effect on ODC.

PMID- 15843385
TI  - Tails of histones in DNA double-strand break repair.
AB  - DNA double-strand breaks (DSBs) are, arguably, the most deleterious form of DNA
      damage. An increasing body of evidence points to the inaccurate or inefficient
      repair of DSBs as a key step in tumorigenesis. Therefore, it is of great
      importance to understand the processes by which DSBs are detected and repaired.
      Clearly, these events must take place in the context of chromatin in vivo, and
      recently, a great deal of progress has been made in understanding the dynamic and
      active role that histone proteins and chromatin modifying activities play in DNA
      DSB repair. Here, we briefly review some of the most common techniques in
      studying DNA DSB responses in vivo, and focus on the contributions of covalent
      modifications of core histone proteins to these DNA DSB responses.

PMID- 15843386
TI  - Evaluation of photo-mutagenicity and photo-cytotoxicity of food coloring agents.
AB  - Pigments extracted from natural products are widely used for food coloration in
      Japan. An investigation concerning the photo-mutagenicity and photo
      carcinogenicity of frequently used colorants in Japan was performed. Colorants
      examined were from Laccifer lacca (lac-color), Coccus cacti (cochineal-color),
      Carthamus tinctorius (carthamus yellow), Gardenia augusta (gardenia yellow and
      gardenia blue), Monascus anka and Monascus purpureus (monascus red), the skin of
      Vitis vinifera and Vitis labrusca (grape-skin color), Tamarindus indica (tamarind
      brown) and Beta vulgaris (beet red). No significant increase in bacterial
      mutation was found when Salmonella typhimurium TA98, TA100 and TA102 were
      simultaneously treated with colorants and subjected to UVA irradiation for 30
      min. When colorant solutions were subjected to UVA irradiation for 4 h,
      irradiated solutions containing lac-color became slightly mutagenic toward
      S.typhimurium TA98 without metabolic activation. A decrease in cell survival
      resulted when WTK-1 cells were subjected to UVA irradiation for 60 min in the
      presence of purpurin at 1 mg/ml. Delayed cytotoxicity was also observed following
      24 h incubation in fresh medium of samples that were subjected to UVA irradiation
      for 60 min in the presence of colorant (carthamus yellow, grape-skin color,
      gardenia blue, cochineal-color, monascus red or purpurin).

PMID- 15843387
TI  - Salmonella/human S9 mutagenicity test: a collaborative study with 58 compounds.
AB  - A large and extensive body of data on the use of human liver S9 fractions in the
      Salmonella mutagenicity test (Ames test) is presented; the data were obtained
      from a collaborative study by JEMS/BMS (Bacterial Mutagenicity Test Study Group)
      members and the Human and Animal Bridging Research Organization (HAB). In this
      study, the mutagenicity of 58 chemicals, many of which were judged to be human
      carcinogens by the IARC, was determined by the Ames test (the pre-incubation
      method at 37 degrees C for 20 min) in the presence of a selected human liver S9
      fraction with a high drug-metabolic activity or a pooled human liver S9 fraction
      with a moderate drug-metabolic activity. For reference, mutagenicity was also
      examined in the presence of a phenobarbital/5,6-benzoflavone-pretreated rat liver
      S9 fraction, which is normally used in mutagenicity testing systems. The
      bacterial test strains consisted of Salmonella typhimurium TA100, TA98 or YG7108.
      The data indicated that the mutagenicity of chemicals in the rat and human liver
      S9 fractions varied considerably, depending on the chemicals in question. In
      addition, a large inter-individual diversity in the mutagenic response to
      mutagens, depending on the chemical structures of the mutagens, was also
      demonstrated using two selected human S9 fractions. Most of the mutagens tested
      in this study (75%; 36 out of 48 compounds that were judged to be mutagenic in at
      least one S9 fraction) were less mutagenic in the presence of the two human S9
      fractions than in the presence of the rat S9 fraction. On the other hand, the
      other compounds (25%), including some aromatic amines and nitrosamines, showed a
      more potent mutagenicity in the presence of either one of the two human S9
      fractions than in the presence of the rat S9 fraction. These data strongly
      suggest that the use of human liver S9 fraction in mutagenicity testing systems
      may be useful for a better understanding of the mutagenic effects of chemicals on
      humans.

PMID- 15843388
TI  - Escherichia coli BTC, a human cytochrome P450 competent tester strain with a high
      sensitivity towards alkylating agents: involvement of alkyltransferases in the
      repair of DNA damage induced by aromatic amines.
AB  - We report here on strain BTC, a new Escherichia coli mutagenicity tester strain
      for the expression of human cytochrome P450 (CYP) with an enhanced sensitivity
      for the detection of alkylating agents. This strain was developed first through
      knocking out of the genes ada and ogt in our previously developed strain BMX100,
      resulting in PD1000. Strain PD1000 demonstrated a significantly higher detection
      sensitivity towards several alkylating agents such as N-nitrosodiethylamine
      (NNdEA), N-nitrosodi-n-propylamine (NNdPA), 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Unexpectedly,
      this strain also showed an enhanced sensitivity towards 2-aminoanthracene (2AA),
      4-aminobiphenyl (4AbPh), 2-aminofluorene (2AF) and 2-nitroanthracene (2NA)
      mutagenicity. Subsequently, our previously developed bi-plasmid system for the co
      expression of a specific human CYP form (CYP1A2, 2A6 or 2E1) with human NADPH
      cytochrome P450 reductase (RED) was introduced in strain PD1000, resulting in
      strains BTC1A2, BTC2A6 and BTC2E1, respectively. The mutagenicity of NNdEA and
      NNK was successfully detected with strains BTC2A6 and BTC2E1 and with strains
      BTC1A2 and BTC2A6, respectively, in contrast to the corresponding MTC (ada+ ogt+)
      CYP strains. The (ada- ogt-) deficient strain BTC1A2 also showed an enhanced
      sensitivity towards the detection of 2AA mutagenicity, when compared with the
      proficient repair strain MTC1A2. This enhancement was much more pronounced with
      strain PD1000 using the rat liver S9 fraction than with strain BTC1A2.

PMID- 15843389
TI  - Assessment of the genotoxic potential of nitric oxide-induced guanine lesions by
      in vitro reactions with Escherichia coli DNA polymerase I.
AB  - It has been suggested that carcinogenesis associated with chronic inflammation
      involves DNA damage by nitric oxide (NO) and other reactive species secreted from
      macrophages and neutrophils. The guanine moiety of DNA reacts with NO, yielding
      two major deamination products: xanthine (Xan) and oxanine (Oxa). Oxa reacts
      further with polyamines and DNA binding proteins to form cross-link adducts. In
      the present study, we characterized the structure of the cross-link adducts of
      Oxa with spermine (Oxa-Sp). Spectrometric analysis of Oxa-Sp adducts showed that
      they are ring-opened adducts of Oxa covalently bonded to the terminal amino
      (major product) and internal imino (minor product) groups of spermine. To assess
      genotoxic potential, Xan, Oxa, Oxa-Sp and an abasic (AP) site were site
      specifically incorporated into oligonucleotide templates. These lesions
      differentially blocked in vitro DNA synthesis catalyzed by DNA polymerase I
      Klenow fragment (Pol I Kf). The relative efficiency of translesion synthesis was
      G (1) > Oxa (0.19) > Xan (0.12) > AP (0.088) > Oxa-Sp (0.035). Primer extension
      assays with a single nucleotide and Pol I Kf revealed that non-mutagenic dCMP was
      inserted most efficiently opposite Xan and Oxa, with the extent of primer
      elongation being 65% for Xan and 68% for Oxa. However, mutagenic nucleotides were
      also inserted. The extent of primer elongation for Xan was 16% with dTMP and 14%
      with dGMP, whereas that for Oxa was 49% with dTMP. For Oxa-Sp, mutagenic dAMP
      (13%) was preferentially inserted. Accordingly, when generated in vivo, Xan and
      Oxa would constitute moderate blocks to DNA synthesis and primarily elicit G:C to
      A:T transitions when bypassed, whereas Oxa-Sp would strongly block DNA synthesis
      and elicit G:C to T:A transversions.

PMID- 15843390
TI  - Induction of micronuclei by lambda-cyhalothrin in Wistar rat bone marrow and gut
      epithelial cells.
AB  - We have investigated the genotoxicity of lambda-cyhalothrin (LCT) (CAS registry
      No. 91465-08-06), a pyrethroid insecticide, in bone marrow cells and in colonic
      crypt epithelial cells of groups of four rats per dose treated in vivo by gavage
      at doses of 0.8, 3.06 and 6.12 mg/kg body weight (body wt). We measured
      genotoxicity using the micronucleus (MN) assay, scoring 2000 polychromatic
      erythrocytes (PCEs) per animal for bone marrow and 1000 colonic crypt epithelial
      cells per animal for the colon. We assessed cytotoxicity in bone marrow by
      calculating the ratio of PCEs to normochromatic erythrocytes, and in the colonic
      crypt epithelium by observing the frequency of binucleate cells and the mitotic
      index in 1000 cells. Apoptosis in colonic crypt epithelial cells was measured by
      observing the frequency of karyorrhexis and karyolysis in 1000 cells. We found
      that LCT induced a statistically significant dose-related increase in MN
      formation in the bone marrow and the colonic crypt. The colonic epithelium was
      more sensitive to the clastogenic effects of LCT than the bone marrow as judged
      by the significantly higher frequencies of MN in the colon than in the bone
      marrow at doses of 3.06 and 6.12 mg/kg body wt.

PMID- 15843391
TI  - The genotoxic effects of hepatitis B virus to host DNA.
AB  - Chronic viral hepatitis is the main cause of chronic liver disease, cirrhosis and
      hepatocellular carcinoma throughout the world. Hepatitis B virus (HBV) has
      mutagenic effects on somatic cells. HBV may be showing these mutagenic effects
      through its viral proteins or through integrating into host DNA. The aim of this
      study was to determine whether HBV has a genotoxic effect on host DNA or not.
      Peripheral blood lymphocytes of 31 chronic HBV patients and 20 chronic HBV
      carriers were cultured in order to make cytogenetic evaluation by observing
      chromosome breakage and cytological evaluation by the micronucleus (MN) test.
      Their results were compared with 20 healthy controls. For each individual, 100
      metaphase chromosome spreads were analysed. Around 190-1091 binucleated cells
      were observed and MN were scored for each individual. Our results showed
      significantly higher frequencies of chromosome breaks in chronic HBV patients and
      in HBV carriers than in the control group. There was no difference in MN scores
      among HBV patients, HBV carriers and healthy carriers. Based on our data, we
      conclude that chronic HBV patients and carriers have chromosomal instability and
      that HBV carriers are as affected as patients because of their same chromosome
      breakage levels.

PMID- 15843392
TI  - Studies on automatic hot gas reader used in the countrywide personnel monitoring
      programme.
AB  - In India, approximately 58,000 radiation workers are monitored using locally made
      CaSO4:Dy teflon embedded thermoluminescence dosemeter (TLD) badge system. The
      automatic hot gas readers developed locally are also used in TL measurements. The
      hot gas reader system has many advantages over the manual readers used previously
      and has completely replaced the manual reader system in all TLD personnel
      monitoring units in India. In the present study, the new reader system is studied
      and a theoretical attempt has been made to interpret the experimentally obtained
      results. The glow curves are generated theoretically and are also plotted
      experimentally. It has been found that the heat capacity of the heating gas,
      which is responsible for the transfer of heat, has a role in deciding the
      position of peak and is verified experimentally using different gas flow rates of
      nitrogen and argon as heating gases in the reader. The theoretical study may also
      be helpful in fitting the experimentally obtained glow curves and, therefore, the
      elimination of unwanted non-radiation-induced contributions, such as dark
      current, electronic spikes, light leakage and triboluminescence that generally
      distort the glow curve shape, can be achieved.

PMID- 15843393
TI  - What we know and what we do not know.

PMID- 15843394
TI  - Infant sleeping position and the sudden infant death syndrome: systematic review
      of observational studies and historical review of recommendations from 1940 to
      2002.
AB  - BACKGROUND: Before the early 1990s, parents were advised to place infants to
      sleep on their front contrary to evidence from clinical research. METHODS: We
      systematically reviewed associations between infant sleeping positions and sudden
      infant death syndrome (SIDS), explored sources of heterogeneity, and compared
      findings with published recommendations. RESULTS: By 1970, there was a
      statistically significantly increased risk of SIDS for front sleeping compared
      with back (pooled odds ratio (OR) 2.93; 95% confidence interval (CI) 1.15, 7.47),
      and by 1986, for front compared with other positions (five studies, pooled OR
      3.00; 1.69-5.31). The OR for front vs the back position was reduced as the
      prevalence of the front position in controls increased. The pooled OR for studies
      conducted before advice changed to avoid front sleeping was 2.95 (95% CI 1.69
      5.15), and after was 6.91 (4.63-10.32). Sleeping on the front was recommended in
      books between 1943 and 1988 based on extrapolation from untested theory.
      CONCLUSIONS: Advice to put infants to sleep on the front for nearly a half
      century was contrary to evidence available from 1970 that this was likely to be
      harmful. Systematic review of preventable risk factors for SIDS from 1970 would
      have led to earlier recognition of the risks of sleeping on the front and might
      have prevented over 10 000 infant deaths in the UK and at least 50 000 in Europe,
      the USA, and Australasia. Attenuation of the observed harm with increased
      adoption of the front position probably reflects a "healthy adopter" phenomenon
      in that families at low risk of SIDS were more likely to adhere to prevailing
      health advice. This phenomenon is likely to be a general problem in the use of
      observational studies for assessing the safety of health promotion.

PMID- 15843395
TI  - Gemins modulate the expression and activity of the SMN complex.
AB  - Reduction in the expression of the survival of motor neurons (SMN) protein
      results in spinal muscular atrophy (SMA), a common motor neuron degenerative
      disease. SMN is part of a large macromolecular complex (the SMN complex) that
      includes at least six additional proteins called Gemins (Gemin2-7). The SMN
      complex is expressed in all cells and is present throughout the cytoplasm and in
      the nucleus where it is concentrated in Gems. The SMN complex plays an essential
      role in the production of spliceosomal small nuclear ribonucleoproteins (snRNPs)
      and likely other RNPs. To study the roles of the individual proteins, we
      systematically reduced the expression of SMN and each of the Gemins (2-6) by RNA
      interference. We show that the reduction of SMN leads to a decrease in snRNP
      assembly, the disappearance of Gems, and to a drastic reduction in the amounts of
      several Gemins. Moreover, reduction of Gemin2 or Gemin6 strongly decreases the
      activity of the SMN complex. These findings demonstrate that other components of
      the SMN complex, in addition to SMN, are critical for the activity of the complex
      and suggest that Gemin2 and Gemin6 are potentially important modifiers of SMA as
      well as potential disease genes for non-SMN motor neuron diseases.

PMID- 15843396
TI  - Alpha-actinin associates with polycystin-2 and regulates its channel activity.
AB  - Polycystin-2 (PC2) is the product of the PKD2 gene, which is mutated in 10-15%
      patients of autosomal dominant polycystic kidney disease (ADPKD). PC2 is an
      integral transmembrane protein and acts as a calcium-permeable cation channel.
      The functional modulation of this channel by other protein partners remains
      largely unknown. In the present study, using a yeast two-hybrid approach, we
      discovered that both intracellular N- and C-termini of PC2 associate with alpha
      actinins, actin-binding and actin-bundling proteins important in cytoskeleton
      organization, cell adhesion, proliferation and migration. The PC2-alpha-actinin
      association was confirmed by in vitro glutathione S-transferase pull-down and dot
      blot overlay assays. In addition, the in vivo interaction between endogenous PC2
      and alpha-actinins was demonstrated by co-immunoprecipitation in human embryonic
      kidney 293 and Madin-Darby canine kidney (MDCK) cells, rat kidney and heart
      tissues and human syncytiotrophoblast (hST) apical membrane vesicles.
      Immunofluorescence experiments showed that PC2 and alpha-actinin were partially
      co-localized in epithelial MDCK and inner medullary collecting duct cells, NIH
      3T3 fibroblasts and hST vesicles. We studied the functional modulation of PC2 by
      alpha-actinin in a lipid bilayer electrophysiology system using in vitro
      translated PC2 and found that alpha-actinin substantially stimulated the channel
      activity of reconstituted PC2. A similar stimulatory effect of alpha-actinin on
      PC2 was also observed when hST vesicles were reconstituted in lipid bilayer.
      Thus, physical and functional interactions between PC2 and alpha-actinin may play
      an important role in abnormal cell adhesion, proliferation and migration observed
      in ADPKD.

PMID- 15843397
TI  - Allele-specific transcript quantification detects haplotypic variation in the
      levels of the SDF-1 transcripts.
AB  - It has been suggested that SDF1-G801A, a single nucleotide polymorphism (SNP) in
      the 3' untranslated region (UTR) of the SDF1 gene, is associated with
      susceptibility to diseases such as AIDS and type-I diabetes. However,
      experimental studies examining the effect of SDF1-G801A on SDF-1 expression have
      not supported its functional importance. In this study, to examine whether other
      polymorphisms have a cis-acting effect on SDF1 expression, we carried out
      haplotype analyses of the SDF1 gene and the allele-specific transcript
      quantification utilizing Epstein-Barr virus-transformed lymphoblastoid cell lines
      with heterozygous genotype for SDF1-G801A. Haplotype-based analyses on the
      proportion of the allele-specific transcripts revealed the presence of haplotypes
      associated with a decreased amount of the transcripts. In addition, we observed
      haplotypic variation in response to dibutyl cyclic AMP and tetradecanoyl phorbol
      acetate that enhances the levels of SDF-1 transcripts probably through activation
      of transcription factors. Showing evidence that polymorphisms other than the SDF1
      G801A have a cis-acting effect on expression of SDF-1 transcripts, the results of
      this study contribute to the interpretation of previous disease-association
      studies and to the selection of SNP markers for future studies. As shown in this
      study, allele-specific transcript quantification coupled with haplotype analyses
      can be an effective tool for detecting cis-acting polymorphisms in expressional
      regulation.

PMID- 15843398
TI  - Huntingtin phosphorylation on serine 421 is significantly reduced in the striatum
      and by polyglutamine expansion in vivo.
AB  - Huntington disease (HD) results from polyglutamine expansion in the huntingtin
      protein (htt). Despite the widespread tissue expression pattern of htt, neuronal
      loss is highly selective to medium spiny neurons of the striatum. Huntingtin is
      phosphorylated on serine-421 (S421) by the pro-survival signaling protein kinase
      Akt (PKB) and this has been previously shown to be protective against the
      toxicity of polyglutamine-expanded htt in cell culture. Using an antibody
      specific for htt phosphorylated on S421, we now demonstrate that htt
      phosphorylation is present at significant levels under normal physiological
      conditions in human and mouse brain. Furthermore, htt phosphorylation shows a
      regional distribution with the highest levels in the cerebellum, less in the
      cortex, and least in the striatum. In cell cultures and in YAC transgenic mice,
      the endogenous phosphorylation of polyglutamine-expanded htt is significantly
      reduced relative to wild-type htt. The presence and pattern of significant htt
      phosphorylation in the brain indicates that this dynamic post-translational
      modification is important for the regulation of htt and may contribute to the
      selective neurodegeneration seen in HD.

PMID- 15843399
TI  - Genome-wide linkage identifies novel modifier loci of aganglionosis in the
      Sox10Dom model of Hirschsprung disease.
AB  - Hirschsprung disease (HSCR) is a complex disorder that exhibits incomplete
      penetrance and variable expressivity due to interactions among multiple
      susceptibility genes. Studies in HSCR families have identified RET-dependent
      modifiers for short-segment HSCR (S-HSCR), but epistatic effects in long-segment
      (L-HSCR) and syndromic cases have not been fully explained. SOX10 mutations
      contribute to syndromic HSCR cases and Sox10 alleles in mice exhibit
      aganglionosis and pigmentary anomalies typical of a subset of HSCR patients
      categorized as Waardenburg-Shah syndrome (WS4, OMIM 277580). Sox10 mutant alleles
      in mice exhibit strain-dependent variation in penetrance and expressivity of
      aganglionic megacolon analogous to the variation observed in patients with
      aganglionosis. In this study, we focused on enteric ganglia deficits in Sox10Dom
      mice and defined aganglionosis as a quantitative trait in Sox10Dom intercross
      progeny to investigate the contribution of strain background to variation in
      enteric nervous system deficits. We observe that the phenotype of Sox10Dom/+
      mutants ranges over a continuum from severe aganglionosis to no detectable
      phenotype in the gut. To systematically identify genes that modulate Sox10
      dependent aganglionosis, we performed a single nucleotide polymorphism-based
      genome scan in Sox10Dom/+ F1 intercross progeny. Our analysis reveals modifier
      loci on mouse chromosomes 3, 5, 8, 11 and 14 with distinct effects on penetrance
      and severity of aganglionosis. Three of these loci on chromosomes 3, 8 and 11 do
      not coincide with previously known aganglionosis susceptibility genes or modifier
      loci and offer new avenues for elucidating the genetic network that modulates
      this complex neurocristopathy.

PMID- 15843400
TI  - Transgenic mice expressing CUG-BP1 reproduce splicing mis-regulation observed in
      myotonic dystrophy.
AB  - Myotonic dystrophy type I (DM1) is an RNA-mediated disease caused by a non-coding
      CTG repeat expansion. A key feature of the RNA-mediated pathogenesis model for DM
      is the disrupted splicing of specific pre-mRNA targets. A link has been
      established between splicing regulation by CUG-BP1, a member of the CELF family
      of proteins, and DM1 pathogenesis. To determine whether increased CUG-BP1
      function was sufficient to model DM, transgenic mice overexpressing CUG-BP1
      (MCKCUG-BP1) in heart and skeletal muscle, two tissues affected in DM1, were
      generated. Histological and electron microscopic analyses of skeletal muscle
      reveal common pathological features with DM tissues: chains of central nuclei,
      degenerating fibers and centralized NADH reactivity. MCKCUG-BP1 mice have
      disrupted splicing of three CELF target pre-mRNAs, cardiac troponin T (Tnnt2),
      myotubularin-related 1 gene (Mtmr1) and the muscle-specific chloride channel
      (Clcn1), consistent with that observed in DM heart and skeletal muscle. The
      results are consistent with a mechanism for DM pathogenesis in which expanded
      repeats result in increased CUG-BP1 activity and/or other CELF family members and
      have trans-dominant effects on specific pre-mRNA targets.

PMID- 15843401
TI  - Sustained ERK1/2 but not STAT1 or 3 activation is required for thanatophoric
      dysplasia phenotypes in PC12 cells.
AB  - Mutations in fibroblast growth factor receptor 3 (FGFR3) cause the most common
      genetic form of short-limbed dwarfism, achondroplasia (ACH), as well as neonatal
      lethal forms, thanatophoric dysplasia (TD) I and II. The causative mutations
      induce graded levels of constitutive activation of the receptor that correspond
      to the severity of the disorder, resulting in premature entry into hypertrophic
      differentiation and reduced proliferation of chondrocytes in developing
      cartilage. Although FGFR3 promotes growth in most tissues, it is a negative
      regulator of endochondral bone growth. Several signaling pathways have been
      implicated in these skeletal disorders including the Ras/MEK/ERK pathway and the
      JAK/STAT, the latter in the most severe phenotypes, however their functional
      relevance remains incompletely understood. Using PC12 cell lines stably
      expressing inducible mutant receptors containing the TDII mutation, K650E,
      sustained activation of ERK1/2 and activation of STAT1 and STAT3, but not STAT5,
      is observed in the absence of ligand. This activation leads to neurite outgrowth,
      a phenotypic readout of constitutive receptor activity, and sustained ERK1/2
      activity is required for this ligand-independent differentiation. To assess the
      functional relevance of STAT activation induced by the mutant receptor, STATs
      were specifically downregulated using RNA-interference. Silencing of STAT1 or 3
      independently or in combination had no significant effect on ligand-independent
      neurite outgrowth, ERK1/2 activation or p21(WAF1/CIP1) protein levels. These
      results support a model in which sustained activation of ERK1/2 is a key
      regulator of the increased transition to hypertrophic differentiation of the
      growth plate, whereas activation of STATs 1 and 3 is not required.

PMID- 15843402
TI  - Genetic models show that parathyroid hormone and 1,25-dihydroxyvitamin D3 play
      distinct and synergistic roles in postnatal mineral ion homeostasis and skeletal
      development.
AB  - In humans, loss-of-function mutations in parathyroid hormone (PTH) and 25
      hydroxyvitamin D3-1alpha-hydroxylase [1alpha(OH)ase] genes lead to isolated
      hypoparathyroidism and vitamin D-dependent rickets type I, respectively. To
      better understand the relative contributions of PTH and 1,25-dihydroxyvitamin D3
      [1,25(OH)2D3] to skeletal and calcium homeostasis, we compared mice with targeted
      disruption of the PTH or 1alpha(OH)ase genes to the double null mutants. Although
      PTH-/- and 1alpha(OH)ase-/- mice displayed only moderate hypocalcemia, PTH-/
      1alpha(OH)ase-/- mice died of tetany with severe hypocalcemia by 3 weeks of age.
      At 2 weeks, PTH-/- mice exhibited only minimal dysmorphic changes, whereas
      1alpha(OH)ase-/- mice displayed epiphyseal dysgenesis which was most severe in
      the double mutants. Although reduced osteoblastic bone formation was seen in both
      mutants, PTH deficiency caused only a slight reduction in long bone length but a
      marked reduction in trabecular bone volume, whereas 1alpha(OH)ase ablation caused
      a smaller reduction in trabecular bone volume but a significant decrease in bone
      length. The results therefore show that PTH plays a predominant role in
      appositional bone growth, whereas 1,25(OH)2D3 acts predominantly on endochondral
      bone formation. Although PTH and 1,25(OH)2D3 independently, but not additively,
      regulate osteoclastic bone resorption, they do affect the renal calcium transport
      pathway cooperatively. Consequently, PTH and 1,25(OH)2D3 exhibit discrete and
      collaborative roles in modulating skeletal and calcium homeostasis and loss of
      the renal component of calcium conservation might be the major factor
      contributing to the lethal hypocalcemia in double mutants.

PMID- 15843403
TI  - Loss of ZMPSTE24 (FACE-1) causes autosomal recessive restrictive dermopathy and
      accumulation of Lamin A precursors.
AB  - Restrictive dermopathy (RD) is characterized by intrauterine growth retardation,
      tight and rigid skin with prominent superficial vessels, bone mineralization
      defects, dysplastic clavicles, arthrogryposis and early neonatal death. In two
      patients affected with RD, we recently reported two different heterozygous
      splicing mutations in the LMNA gene, leading to the production and accumulation
      of truncated Prelamin A. In other patients, a single nucleotide insertion was
      identified in ZMPSTE24. This variation is located in a homopolymeric repeat of
      thymines and introduces a premature termination codon. ZMPSTE24 encodes an
      endoprotease essential for the post-translational cleavage of the Lamin A
      precursor and the production of mature Lamin A. However, the autosomal recessive
      inheritance of RD suggested that a further molecular defect was present either in
      the second ZMPSTE24 allele or in another gene involved in Lamin A processing.
      Here, we report new findings in RD linked to ZMPSTE24 mutations. Ten RD patients
      were analyzed including seven from a previous series and three novel patients.
      All were found to be either homozygous or compound heterozygous for ZMPSTE24
      mutations. We report three novel 'null' mutations as well as the recurrent
      thymine insertion. In all cases, we find a complete absence of both ZMPSTE24 and
      mature Lamin A associated with Prelamin A accumulation. Thus, RD is either a
      primary or a secondary laminopathy, caused by dominant de novo LMNA mutations or,
      more frequently, recessive null ZMPSTE24 mutations, most of which lie in a
      mutation hotspot within exon 9. The accumulation of truncated or normal length
      Prelamin A is, therefore, a shared pathophysiological feature in recessive and
      dominant RD. These findings have an important impact on our knowledge of the
      pathophysiology in Progeria and related disorders and will help direct the
      development of therapeutic approaches.

PMID- 15843404
TI  - Altered pre-lamin A processing is a common mechanism leading to lipodystrophy.
AB  - Lipodystrophies are a heterogeneous group of human disorders characterized by the
      anomalous distribution of body fat associated with insulin resistance and altered
      lipid metabolism. The pathogenetic mechanism of inherited lipodystrophies is not
      yet clear; at the molecular level they have been linked to mutations of lamin
      A/C, peroxisome proliferator-activated receptor (PPARgamma) and other seemingly
      unrelated proteins. In this study, we examined lamin A/C processing in three
      laminopathies characterized by lipodystrophic phenotypes: Dunnigan type familial
      partial lipodystrophy, mandibuloacral dysplasia and atypical Werner's syndrome.
      We found that the lamin A precursor was specifically accumulated in lipodystrophy
      cells. Pre-lamin A was located at the nuclear envelope and co-localized with the
      adipocyte transcription factor sterol regulatory element binding protein 1
      (SREBP1). Using co-immunoprecipitation experiments, we obtained the first
      demonstration of an in vivo interaction between SREBP1 and pre-lamin A. Binding
      of SREBP1 to the lamin A precursor was detected in patient fibroblasts as well as
      in control fibroblasts forced to accumulate pre-lamin A by farnesylation
      inhibitors. In contrast, SREBP1 did not interact in vivo with mature lamin A or C
      in cultured fibroblasts. To gain insights into the effect of pre-lamin A
      accumulation in adipose tissue, we inhibited lamin A precursor processing in 3T3
      L1 pre-adipocytes. Our results show that pre-lamin A sequesters SREBP1 at the
      nuclear rim, thus decreasing the pool of active SREBP1 that normally activates
      PPARgamma and causing impairment of pre-adipocyte differentiation. This defect
      can be rescued by treatment with troglitazone, a known PPARgamma ligand
      activating the adipogenic program.

PMID- 15843405
TI  - Hydrolethalus syndrome is caused by a missense mutation in a novel gene HYLS1.
AB  - Hydrolethalus syndrome (HLS) is an autosomal recessive lethal malformation
      syndrome characterized by multiple developmental defects of fetus. We have
      earlier mapped and restricted the HLS region to a critical 1 cM interval on 11q23
      25. The linkage disequilibrium (LD) and haplotype analyses of single nucleotide
      polymorphism (SNP) markers helped to further restrict the HLS locus to 476 kb
      between genes PKNOX2 and DDX25. An HLS associated mutation was identified in a
      novel regional transcript (GenBank accession no. FLJ32915), referred to here as
      the HYLS1 gene. The identified A to G transition results in a D211G change in the
      299 amino acid polypeptide with unknown function. The HYLS1 gene shows
      alternative splicing and the transcript is found in multiple tissues during fetal
      development. In situ hybridization shows spatial and temporal distributions of
      transcripts in good agreement with the tissue phenotype of HLS patients.
      Immunostaining of in vitro expressed polypeptides from wild-type (WT) cDNA
      revealed cytoplasmic staining, whereas mutant polypeptides became localized in
      distinct nuclear structures, implying a disturbed cellular localization of the
      mutant protein. The Drosophila melanogaster model confirmed these findings and
      provides evidence for the significance of the mutation both in vitro and in vivo.

PMID- 15843406
TI  - The retinoblastoma gene pathway regulates the postmitotic state of hair cells of
      the mouse inner ear.
AB  - Precursors of cochlear and vestibular hair cells of the inner ear exit the cell
      cycle at midgestation. Hair cells are mitotically quiescent during late-embryonic
      differentiation stages and postnatally. We show here that the retinoblastoma gene
      Rb and the encoded protein pRb are expressed in differentiating and mature hair
      cells. In addition to Rb, the cyclin dependent kinase inhibitor (CKI) p21 is
      expressed in developing hair cells, suggesting that p21 is an upstream effector
      of pRb activity. p21 apparently cooperates with other CKIs, as p21-null mice
      exhibited an unaltered inner ear phenotype. By contrast, Rb inactivation led to
      aberrant hair cell proliferation, as analysed at birth in a loss-of
      function/transgenic mouse model. Supernumerary hair cells expressed various cell
      type-specific differentiation markers, including components of stereocilia. The
      extent of alterations in stereociliary bundle morphology ranged from near-normal
      to severe disorganization. Apoptosis contributed to the mutant phenotype, but did
      not compensate for the production of supernumerary hair cells, resulting in
      hyperplastic sensory epithelia. The Rb-null-mediated proliferation led to a
      distinct pathological phenotype, including multinucleated and enlarged hair
      cells, and infiltration of hair cells into the mesenchyme. Our findings
      demonstrate that the pRb pathway is required for hair cell quiescence and that
      manipulation of the cell cycle machinery disrupts the coordinated development
      within the inner ear sensory epithelia.

PMID- 15843407
TI  - T-box genes coordinate regional rates of proliferation and regional specification
      during cardiogenesis.
AB  - Mutations in T-box genes are the cause of several congenital diseases and are
      implicated in cancer. Tbx20-null mice exhibit severely hypoplastic hearts and
      express Tbx2, which is normally restricted to outflow tract and atrioventricular
      canal, throughout the heart. Tbx20 mutant hearts closely resemble those seen in
      mice overexpressing Tbx2 in myocardium, suggesting that upregulation of Tbx2 can
      largely account for the cardiac phenotype in Tbx20-null mice. We provide evidence
      that Tbx2 is a direct target for repression by Tbx20 in developing heart. We have
      also found that Tbx2 directly binds to the Nmyc1 promoter in developing heart,
      and can repress expression of the Nmyc1 promoter in transient transfection
      studies. Repression of Nmyc1 (N-myc) by aberrantly regulated Tbx2 can account in
      part for the observed cardiac hypoplasia in Tbx20 mutants. Nmyc1 is required for
      growth and development of multiple organs, including the heart, and
      overexpression of Nmyc1 is associated with childhood tumors. Despite its clinical
      relevance, the factors that regulate Nmyc1 expression during development are
      unknown. Our data present a paradigm by which T-box proteins regulate regional
      differences in Nmyc1 expression and proliferation to effect organ morphogenesis.
      We present a model whereby Tbx2 directly represses Nmyc1 in outflow tract and
      atrioventricular canal of the developing heart, resulting in relatively low
      proliferation. In chamber myocardium, Tbx20 represses Tbx2, preventing repression
      of Nmyc1 and resulting in relatively high proliferation. In addition to its role
      in regulating regional proliferation, we have found that Tbx20 regulates
      expression of a number of genes that specify regional identity within the heart,
      thereby coordinating these two important aspects of organ development.

PMID- 15843408
TI  - crossveinless-c is a RhoGAP required for actin reorganisation during
      morphogenesis.
AB  - Members of the Rho family of small GTPases are required for many of the
      morphogenetic processes required to shape the animal body. The activity of this
      family is regulated in part by a class of proteins known as RhoGTPase Activating
      Proteins (RhoGAPs) that catalyse the conversion of RhoGTPases to their inactive
      state. In our search for genes that regulate Drosophila morphogenesis, we have
      isolated several lethal alleles of crossveinless-c (cv-c). Molecular
      characterisation reveals that cv-c encodes the RhoGAP protein RhoGAP88C. During
      embryonic development, cv-c is expressed in tissues undergoing morphogenetic
      movements; phenotypic analysis of the mutants reveals defects in the
      morphogenesis of these tissues. Genetic interactions between cv-c and RhoGTPase
      mutants indicate that Rho1, Rac1 and Rac2 are substrates for Cv-c, and suggest
      that the substrate specificity might be regulated in a tissue-dependent manner.
      In the absence of cv-c activity, tubulogenesis in the renal or Malpighian tubules
      fails and they collapse into a cyst-like sack. Further analysis of the role of cv
      c in the Malpighian tubules demonstrates that its activity is required to
      regulate the reorganisation of the actin cytoskeleton during the process of
      convergent extension. In addition, overexpression of cv-c in the developing
      tubules gives rise to actin-associated membrane extensions. Thus, Cv-c function
      is required in tissues actively undergoing morphogenesis, and we propose that its
      role is to regulate RhoGTPase activity to promote the coordinated organisation of
      the actin cytoskeleton, possibly by stabilising plasma membrane/actin
      cytoskeleton interactions.

PMID- 15843409
TI  - Tbx20 dose-dependently regulates transcription factor networks required for mouse
      heart and motoneuron development.
AB  - To elucidate the function of the T-box transcription factor Tbx20 in mammalian
      development, we generated a graded loss-of-function series by transgenic RNA
      interference in entirely embryonic stem cell-derived mouse embryos. Complete
      Tbx20 knockdown resulted in defects in heart formation, including hypoplasia of
      the outflow tract and right ventricle, which derive from the anterior heart field
      (AHF), and decreased expression of Nkx2-5 and Mef2c, transcription factors
      required for AHF formation. A mild knockdown led to persistent truncus arteriosus
      (unseptated outflow tract) and hypoplastic right ventricle, entities similar to
      human congenital heart defects, and demonstrated a critical requirement for Tbx20
      in valve formation. Finally, an intermediate knockdown revealed a role for Tbx20
      in motoneuron development, specifically in the regulation of the transcription
      factors Isl2 and Hb9, which are important for terminal differentiation of
      motoneurons. Tbx20 could activate promoters/enhancers of several genes in
      cultured cells, including the Mef2c AHF enhancer and the Nkx2-5 cardiac enhancer.
      The Mef2c AHF enhancer relies on Isl1- and Gata-binding sites. We identified a
      similar Isl1 binding site in the Nkx2-5 AHF enhancer, which in transgenic mouse
      embryos was essential for activity in a large part of the heart, including the
      outflow tract. Tbx20 synergized with Isl1 and Gata4 to activate both the Mef2c
      and Nkx2-5 enhancers, thus providing a unifying mechanism for gene activation by
      Tbx20 in the AHF. We conclude that Tbx20 is positioned at a critical node in
      transcription factor networks required for heart and motoneuron development where
      it dose-dependently regulates gene expression.

PMID- 15843410
TI  - Neural crest determination by co-activation of Pax3 and Zic1 genes in Xenopus
      ectoderm.
AB  - A number of regulatory genes have been implicated in neural crest development.
      However, the molecular mechanism of how neural crest determination is initiated
      in the exact ectodermal location still remains elusive. Here, we show that the
      cooperative function of Pax3 and Zic1 determines the neural crest fate in the
      amphibian ectoderm. Pax3 and Zic1 are expressed in an overlapping manner in the
      presumptive neural crest area of the Xenopus gastrula, even prior to the onset of
      the expression of the early bona fide neural crest marker genes Foxd3 and Slug.
      Misexpression of both Pax3 and Zic1 together efficiently induces ectopic neural
      crest differentiation in the ventral ectoderm, whereas overexpression of either
      one of them only expands the expression of neural crest markers within the
      dorsolateral ectoderm. The induction of neural crest differentiation by Pax3 and
      Zic1 requires Wnt signaling. Loss-of-function studies in vivo and in the animal
      cap show that co-presence of Pax3 and Zic1 is essential for the initiation of
      neural crest differentiation. Thus, co-activation of Pax3 and Zic1, in concert
      with Wnt, plays a decisive role for early neural crest determination in the
      correct place of the Xenopus ectoderm.

PMID- 15843411
TI  - Sirenomelia in Bmp7 and Tsg compound mutant mice: requirement for Bmp signaling
      in the development of ventral posterior mesoderm.
AB  - Sirenomelia or mermaid-like phenotype is one of the principal human congenital
      malformations that can be traced back to the stage of gastrulation. Sirenomelia
      is characterized by the fusion of the two hindlimbs into a single one. In the
      mouse, sirens have been observed in crosses between specific strains and as the
      consequence of mutations that increase retinoic acid levels. We report that the
      loss of bone morphogenetic protein 7 (Bmp7) in combination with a half dose or
      complete loss of twisted gastrulation (Tsg) causes sirenomelia in the mouse. Tsg
      is a Bmp- and chordin-binding protein that has multiple effects on Bmp metabolism
      in the extracellular space; Bmp7 is one of many Bmps and is shown here to bind to
      Tsg. In Xenopus, co-injection of Tsg and Bmp7 morpholino oligonucleotides (MO)
      has a synergistic effect, greatly inhibiting formation of ventral mesoderm and
      ventral fin tissue. In the mouse, molecular marker studies indicate that the
      sirenomelia phenotype is associated with a defect in the formation of
      ventroposterior mesoderm. These experiments demonstrate that dorsoventral
      patterning of the mouse posterior mesoderm is regulated by Bmp signaling, as is
      the case in other vertebrates. Sirens result from a fusion of the hindlimb buds
      caused by a defect in the formation of ventral mesoderm.

PMID- 15843412
TI  - PAT-related amino acid transporters regulate growth via a novel mechanism that
      does not require bulk transport of amino acids.
AB  - Growth in normal and tumour cells is regulated by evolutionarily conserved
      extracellular inputs from the endocrine insulin receptor (InR) signalling pathway
      and by local nutrients. Both signals modulate activity of the intracellular TOR
      kinase, with nutrients at least partly acting through changes in intracellular
      amino acid levels mediated by amino acid transporters. We show that in
      Drosophila, two molecules related to mammalian proton-assisted SLC36 amino acid
      transporters (PATs), CG3424 and CG1139, are potent mediators of growth. These
      transporters genetically interact with TOR and other InR signalling components,
      indicating that they control growth by directly or indirectly modulating the
      effects of TOR signalling. A mutation in the CG3424 gene, which we have named
      pathetic (path), reduces growth in the fly. In a heterologous Xenopus oocyte
      system, PATH also activates the TOR target S6 kinase in an amino acid-dependent
      way. However, functional analysis reveals that PATH has an extremely low capacity
      and an exceptionally high affinity compared with characterised human PATs and the
      CG1139 transporter. PATH and potentially other PAT-related transporters must
      therefore control growth via a mechanism that does not require bulk transport of
      amino acids into the cell. As PATH is likely to be saturated in vivo, we propose
      that one specialised function of high-affinity PAT-related molecules is to
      maintain growth as local nutrient levels fluctuate during development.

PMID- 15843413
TI  - Six3 functions in anterior neural plate specification by promoting cell
      proliferation and inhibiting Bmp4 expression.
AB  - Although it is well established that Six3 is a crucial regulator of vertebrate
      eye and forebrain development, it is unknown whether this homeodomain protein has
      a role in the initial specification of the anterior neural plate. In this study,
      we show that exogenous Six3 can expand the anterior neural plate in both Xenopus
      and zebrafish, and that this occurs in part through Six3-dependent
      transcriptional regulation of the cell cycle regulators cyclinD1 and p27Xic1, as
      well as the anti-neurogenic genes Zic2 and Xhairy2. However, Six3 can still
      expand the neural plate in the presence of cell cycle inhibitors and we show that
      this is likely to be due to its ability to repress the expression of Bmp4 in
      ectoderm adjacent to the anterior neural plate. Furthermore, exogenous Six3 is
      able to restore the size of the anterior neural plate in chordino mutant
      zebrafish, indicating that it has the ability to promote anterior neural
      development by antagonising the activity of the BMP pathway. On its own, Six3 is
      unable to induce neural tissue in animal caps, but it can do so in combination
      with Otx2. These results suggest a very early role for Six3 in specification of
      the anterior neural plate, through the regulation of cell proliferation and the
      inhibition of BMP signalling.

PMID- 15843415
TI  - Loss of patched and disruption of granule cell development in a pre-neoplastic
      stage of medulloblastoma.
AB  - Medulloblastoma is the most common malignant brain tumor in children. It is
      thought to result from the transformation of granule cell precursors (GCPs) in
      the developing cerebellum, but little is known about the early stages of the
      disease. Here, we identify a pre-neoplastic stage of medulloblastoma in patched
      heterozygous mice, a model of the human disease. We show that pre-neoplastic
      cells are present in the majority of patched mutants, although only 16% of these
      mice develop tumors. Pre-neoplastic cells, like tumor cells, exhibit activation
      of the Sonic hedgehog pathway and constitutive proliferation. Importantly, they
      also lack expression of the wild-type patched allele, suggesting that loss of
      patched is an early event in tumorigenesis. Although pre-neoplastic cells
      resemble GCPs and tumor cells in many respects, they have a distinct molecular
      signature. Genes that mark the pre-neoplastic stage include regulators of
      migration, apoptosis and differentiation, processes crucial for normal
      development but previously unrecognized for their role in medulloblastoma. The
      identification and molecular characterization of pre-neoplastic cells provides
      insight into the early steps in medulloblastoma formation, and may yield
      important markers for early detection and therapy of this disease.

PMID- 15843414
TI  - Murine T-box transcription factor Tbx20 acts as a repressor during heart
      development, and is essential for adult heart integrity, function and adaptation.
AB  - The genetic hierarchies guiding lineage specification and morphogenesis of the
      mammalian embryonic heart are poorly understood. We now show by gene targeting
      that murine T-box transcription factor Tbx20 plays a central role in these
      pathways, and has important activities in both cardiac development and adult
      function. Loss of Tbx20 results in death of embryos at mid-gestation with grossly
      abnormal heart morphogenesis. Underlying these disturbances was a severely
      compromised cardiac transcriptional program, defects in the molecular pre
      pattern, reduced expansion of cardiac progenitors and a block to chamber
      differentiation. Notably, Tbx20-null embryos showed ectopic activation of Tbx2
      across the whole heart myogenic field. Tbx2 encodes a transcriptional repressor
      normally expressed in non-chamber myocardium, and in the atrioventricular canal
      it has been proposed to inhibit chamber-specific gene expression through
      competition with positive factor Tbx5. Our data demonstrate a repressive activity
      for Tbx20 and place it upstream of Tbx2 in the cardiac genetic program. Thus,
      hierarchical, repressive interactions between Tbx20 and other T-box genes and
      factors underlie the primary lineage split into chamber and non-chamber
      myocardium in the forming heart, an early event upon which all subsequent
      morphogenesis depends. Additional roles for Tbx20 in adult heart integrity and
      contractile function were revealed by in-vivo cardiac functional analysis of
      Tbx20 heterozygous mutant mice. These data suggest that mutations in human
      cardiac transcription factor genes, possibly including TBX20, underlie both
      congenital heart disease and adult cardiomyopathies.

PMID- 15843416
TI  - Development of the mammalian urethra is controlled by Fgfr2-IIIb.
AB  - Development of external genitalia in mammalian embryos requires tight
      coordination of a complex series of morphogenetic events involving outgrowth,
      proximodistal and dorsoventral patterning, and epithelial tubulogenesis.
      Hypospadias is a congenital defect of the external genitalia that results from
      failure of urethral tube closure. Although this is the second most common birth
      defect in humans, affecting one in every 250 children, the molecular mechanisms
      that regulate morphogenesis of the mammalian urethra are poorly understood. We
      report that mice lacking the IIIb isoform of fibroblast growth factor receptor 2
      (Fgfr2) exhibit severe hypospadias. Urethral signaling regions, as indicated by
      Shh and Fgf8 expression, are established in Fgfr2-IIIb null mice; however, cell
      proliferation arrests prematurely and maturation of the urethral epithelium is
      disrupted. Fgfr2-IIIb-/- mutants fail to maintain the progenitor cell population
      required for uroepithelial renewal during tubular morphogenesis. In addition, we
      show that antagonism of the androgen receptor (AR) leads to loss of Fgfr2-IIIb
      and Fgf10 expression in the urethra, and an associated hypospadias phenotype,
      suggesting that these genes are downstream targets of AR during external genital
      development. Genitourinary defects resulting from disruption of AR activity, by
      either genetic or environmental factors, may therefore involve negative
      regulation of the Fgfr2 pathway. This represents the first example of how the
      developing genitourinary system integrates cues from systemically circulating
      steroid hormones with a locally expressed growth factor pathway.

PMID- 15843417
TI  - Simultaneous recordings of oesophageal acid exposure with conventional pH
      monitoring and a wireless system (Bravo).
AB  - OBJECTIVES: Oesophageal pH monitoring is a useful test for the diagnosis of
      gastro-oesophageal reflux disease (GORD) but has some limitations related to the
      nasopharyngeal electrode. Recently, a telemetric catheter free system (CFS)
      (Bravo; Medtronic) was developed. The aim of this study was to determine the
      concordance of data between the conventional pH measurement system (CPHMS) and
      the CFS Bravo. METHODS: Forty patients with symptoms suggestive of GORD underwent
      24 hour oesophageal pH monitoring using the CPHMS with a nasopharyngeal electrode
      and the Bravo CFS simultaneously. The sensitive tips of both electrodes were
      positioned at the same level under fluoroscopy. In addition to automatic
      analysis, each reflux episode was checked visually and characterised. RESULTS:
      There was a significant correlation (r = 0.87, p < 0.0001) between the 24 hour
      oesophageal acid exposures recorded by the CPHMS and the CFS. Twenty four hour
      oesophageal acid exposure was significantly lower with the CFS than with the
      CPHMS (2.4 (0.4-8.7) v 3.6 (0.7-8.6); p < 0.0001). Consequently, with the CFS,
      the cut off level for the diagnosis of GORD, as calculated from the regression
      equation, was 2.9% (for the 4.2% cut off determined in controls with the CPHMS).
      After this adjustment, concordance of the diagnosis of GORD was 88% (kappa
      0.760). Diagnosis of GORD was established in more patients with the CFS 48 hour
      results than with the 24 hour results. CONCLUSIONS: Despite strong correlations
      between oesophageal acid exposure recorded with the two devices, the Bravo CFS
      significantly under recorded acid exposure compared with the CPHMS. Provided some
      correcting factors are used, the Bravo CFS can improve the sensitivity of pHmetry
      for the diagnosis of GORD by allowing more prolonged recordings.

PMID- 15843418
TI  - Gastric motor effects of peptide and non-peptide ghrelin agonists in mice in vivo
      and in vitro.
AB  - BACKGROUND AND AIMS: The gastroprokinetic activities of ghrelin, the natural
      ligand of the growth hormone secretagogue receptor (GHS-R), prompted us to
      compare the effect of ghrelin with that of synthetic peptide (growth hormone
      releasing peptide 6 (GHRP-6)) and non-peptide (capromorelin) GHS-R agonists both
      in vivo and in vitro. METHODS: In vivo, the dose dependent effects (1-150
      nmol/kg) of ghrelin, GHRP-6, and capromorelin on gastric emptying were measured
      by the 14C octanoic breath test which was adapted for use in mice. The effect of
      atropine, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME), or D-Lys3
      GHRP-6 (GHS-R antagonist) on the gastroprokinetic effect of capromorelin was also
      investigated. In vitro, the effect of the GHS-R agonists (1 microM) on electrical
      field stimulation (EFS) induced responses was studied in fundic strips in the
      absence and presence of L-NAME. RESULTS: Ghrelin, GHRP-6, and capromorelin
      accelerated gastric emptying in an equipotent manner, with bell-shaped dose
      response relationships. In the presence of atropine or l-NAME, which delayed
      gastric emptying, capromorelin failed to accelerate gastric emptying. D-Lys3-GHRP
      6 also delayed gastric emptying but did not effectively block the action of the
      GHS-R agonists, but this may be related to interactions with other receptors. EFS
      of fundic strips caused frequency dependent relaxations that were not modified by
      the GHS-R agonists. L-NAME turned EFS induced relaxations into cholinergic
      contractions that were enhanced by ghrelin, GHRP-6, and capromorelin. CONCLUSION:
      The 14C octanoic breath test is a valuable technique to evaluate drug induced
      effects on gastric emptying in mice. Peptide and non-peptide GHS-R agonists
      accelerate gastric emptying of solids in an equipotent manner through activation
      of GHS receptors, possibly located on local cholinergic enteric nerves.

PMID- 15843419
TI  - Birth size and colorectal cancer risk: a prospective population based study.
AB  - OBJECTIVE: To study whether birth size influences colorectal cancer risk in
      adulthood. DESIGN: A cohort of Norwegian men and women identified from midwives'
      birth records with long term cancer follow up through the Norwegian Cancer
      Registry. SETTING: St Olav's University Hospital, Trondheim, Norway.
      PARTICIPANTS: 16,016 women and 19 681 men born between 1920 and 1958 and alive in
      1960. OUTCOME MEASURES: Incidence rate ratios (RRs) for colorectal cancer with
      95% confidence intervals (CIs) and two sided p values for trend across categories
      of birth dimensions. RESULTS: Men whose birth length was less than 51 cm had a
      nearly twofold higher risk of colorectal cancer (RR 1.9 (95% CI 1.0-3.7))
      compared with men who were 53 cm or more, after adjustment for birth cohort,
      maternal age at childbearing, length of gestation, gestational hypertension or
      pre-eclampsia, birth order, maternal height, and indicators of maternal
      socioeconomic status. The association displayed a linear trend across categories
      of birth length (p(trend) = 0.03). Among men, similar associations were found for
      birth weight and head circumference, but for women there was no association
      between any of these birth dimensions and risk of colorectal cancer. CONCLUSION:
      The results suggest that among men, but not women, being relatively short at
      birth is associated with increased risk of colorectal cancer in adulthood,
      indicating that intrauterine growth could be important for colorectal
      carcinogenesis.

PMID- 15843420
TI  - DLG5 variants do not influence susceptibility to inflammatory bowel disease in
      the Scottish population.
AB  - INTRODUCTION: Recent data have suggested that specific haplotypic variants of the
      DLG5 gene on chromosome 10q23 may be associated with susceptibility to
      inflammatory bowel disease (IBD) in Germany. Haplotype D, notably characterised
      by the presence of a G-->A substitution at nucleotide 113, was associated with
      susceptibility to Crohn's disease (CD) whereas an extended haplotype A conferred
      protection. AIMS: Association of DLG5 haplotypic variants with disease
      susceptibility, genotype-phenotype relationships, and epistasis with CARD15 was
      investigated in the Scottish population. PATIENTS AND METHODS: A total of 374 CD,
      305 ulcerative colitis (UC), and 294 healthy controls (HC) were studied.
      Genotyping for the variants rs1248696 (113A, representing haplotype D) and the
      single nucleotide polymorphism tag rs2289311 (representing haplotype A) were
      typed using the Taqman system. RESULTS: On analysis of the DLG5 variant 113A,
      there were no associations with IBD when allelic frequency (11.4% IBD v 13.2% HC;
      p = 0.30) and carrier frequency (19.2% IBD v 24.6% HC; p = 0.069) were analysed.
      No associations were observed between 113A variant allelic frequency (p = 0.37),
      carrier frequency (p = 0.057), and CD. In fact, 113A heterozygosity rates were
      lower in CD (16%) and IBD (16.9%) than in HC (23%) (p = 0.029 and p = 0.033,
      respectively). No associations between DLG5 and UC were observed. Haplotype A was
      not protective and there was no evidence of epistasis between DLG5 and CARD15.
      CONCLUSIONS: The present data contrast strongly with previous data from Germany.
      DLG5 113A is not associated with disease susceptibility and haplotype A does not
      confer resistance. Further work is required to evaluate the significance of DLG5
      in other populations from geographically diverse regions.

PMID- 15843421
TI  - The prognostic significance of K-ras, p53, and APC mutations in colorectal
      carcinoma.
AB  - BACKGROUND: Accumulation of molecular alterations, including mutations in Kirsten
      ras (K-ras), p53, and adenomatous polyposis coli (APC), contribute to colorectal
      carcinogenesis. Our group has previously characterised a panel of sporadic
      colorectal adenocarcinomas for mutations in these three genes and has shown that
      p53 and K-ras mutations rarely occur in the same colorectal tumour. This suggests
      that mutations in these genes are on separate pathways to colorectal cancer
      development and may influence patient prognosis independently. AIMS: To correlate
      the presence or absence of mutations in K-ras, p53, and APC with survival in a
      cohort of colorectal cancer patients. PATIENTS: A series of 107 inpatients
      treated surgically for colorectal cancer in Tayside, Scotland between November
      1997 and December 1999. METHODS: Colorectal tumours were characterised for
      mutations in K-ras, p53, and APC. Kaplan-Meier survival curves were constructed
      using overall survival and disease specific survival as the primary end points.
      Patient survival was analysed using the log rank test and Cox proportional
      hazards model. RESULTS: Patients with K-ras mutations had significantly poorer
      overall survival than patients without K-ras mutations (p = 0.0098). Multivariate
      analysis correcting for Dukes' stage, age, and sex confirmed this (hazard ratio
      2.9 (95% confidence interval 1.4-6.2); p = 0.0040). K-ras mutations were also
      significantly associated with poorer disease specific survival. The presence of
      APC and p53 mutations did not affect survival in this cohort of patients (p =
      0.9034 and p = 0.8290, respectively). CONCLUSIONS: Our data indicate that the
      presence of K-ras mutations predicts poor patient prognosis in colorectal cancer,
      independently of tumour stage.

PMID- 15843422
TI  - Distinct cerebral lesions in sporadic and 'D90A' SOD1 ALS: studies with
      [11C]flumazenil PET.
AB  - Five to ten percent of amyotrophic lateral sclerosis (ALS) cases are associated
      with mutations of the superoxide dismutase-1 (SOD1) gene, and the 'D90A' mutation
      is associated with a unique phenotype and markedly slower disease progression
      (mean survival time 14 years). Relative sparing of inhibitory cortical neuronal
      circuits might be one mechanism contributing to the slower progression in
      patients homozygous for the D90A mutation (homD90A). The GABA(A) receptor PET
      ligand [11C]flumazenil has demonstrated motor and extra-motor cortical changes in
      sporadic ALS. In this study, we used [11C]flumazenil PET to explore differences
      in the pattern of cortical involvement between sporadic and genetically
      homogeneous ALS groups. Twenty-four sporadic ALS (sALS) and 10 homD90A patients
      underwent [11C]flumazenil PET of the brain. In addition, two subjects homozygous
      for the D90A mutation, but without symptoms or signs ('pre-symptomatic', psD90A),
      also underwent imaging. Results for each group were compared with those for 24
      healthy controls of similar age. Decreases in the binding of [11C]flumazenil in
      the sALS group were found within premotor regions, motor cortex and posterior
      motor association areas. In the homD90A group of ALS patients, however, decreases
      were concentrated in the left fronto-temporal junction and anterior cingulate
      gyrus. In the two psD90A subjects, a small focus of reduced [11C]flumazenil
      binding at the left fronto-temporal junction was seen, similar to the pattern
      seen in the clinically affected patients. Within the sALS group, there was no
      statistically significant association between decreases in cortical
      [11C]flumazenil binding and revised ALS functional rating scale (ALSFRS-R score),
      whereas the upper motor neuron (UMN) score correlated with widespread and marked
      cortical decreases over the dominant hemisphere. In the homD90A group, there was
      a stronger statistical association between reduced cortical [11C]flumazenil
      binding and the ALSFRS-R, rather than the UMN, score, and also with disease
      duration. This study provides evidence for differences in the distribution of
      reduced cortical [11C]flumazenil binding in homD90A compared with sALS patients.
      We hypothesize that this might reflect differences in cortical neuronal
      vulnerability.

PMID- 15843423
TI  - Clinical deficits correlate with regional cerebral atrophy in progressive
      supranuclear palsy.
AB  - Most cerebral imaging studies of patients with progressive supranuclear palsy
      (PSP) have noted subtle atrophy, although the full extent of atrophy and any
      correlates to clinical features have not been determined. We used voxel-based
      morphometry analysis of grey matter, white matter and CSF on MRI brain scans to
      map the statistical probability of regional tissue atrophy in 21 patients with
      PSP, 17 patients with Parkinson's disease and 23 controls. PSP and Parkinson's
      disease cohorts were selected to approximate the mid-stages of their respective
      disease courses. Where regions of significant tissue atrophy were identified in a
      disease group relative to controls, the probability of tissue loss within those
      regions was correlated with global indices of motor disability, and behavioural
      and cognitive disturbance for that disease group. Minimal regional atrophy was
      observed in Parkinson's disease. PSP could be distinguished from both controls
      and Parkinson's disease by symmetrical tissue loss in the frontal cortex (maximal
      in the orbitofrontal and medial frontal cortices), subcortical nuclei (midbrain,
      caudate and thalamic) as well as periventricular white matter. For PSP, motor
      deficits correlated with atrophy of the caudate and motor cingulate, while
      behavioural changes related to atrophy in the orbitofrontal cortex and midbrain.
      These data suggest that intrinsic neurodegeneration of specific subcortical
      nuclei and frontal cortical subregions together contribute to motor and
      behavioural disturbances in PSP and differentiate this disorder from Parkinson's
      disease within 2-4 years of symptom onset.

PMID- 15843424
TI  - A multigenerational pedigree of late-onset Alzheimer's disease implies new
      genetic causes.
AB  - We describe the clinical phenotype and pathology of a new autosomal dominant late
      onset familial form of Alzheimer's disease in four extensive kindred originated
      in a genetically isolated population. Twelve affected and 16 unaffected members
      of these kindred were examined clinically, and a brain post-mortem study was
      carried out in one case. The preliminary genetic assessment included complex
      segregation analysis, evaluation of the power to detect linkage, and exclusion of
      candidate genes. Dementia has been recorded for six generations in ancestors of
      examined cases. Review of death certificates allowed linking of all subjects in
      four extensive pedigrees. Affected individuals examined had progressive memory
      loss with onset between 57 and 74 years of age, along with seizures, myoclonus
      and parkinsonism in advanced stages. The brain of the case examined post-mortem
      showed widespread neocortical neuritic plaques and neurofibrillary tangles (stage
      VI of Braak), amyloid angiopathy, and Lewy bodies restricted to limbic areas.
      Sequencing exons 16 and 17 of amyloid precursor protein, and exons 4-12 of
      presenilin 1 and presenilin 2 genes did not disclose any mutations. Genotyping
      with markers D21S265, D14S71, D14S77, D1S2850 and D1S479 located 1-3 cM from the
      previously reported genes further excluded linkage to these genes. Seven out of
      12 cases were apolipoprotein E (APOE) epsilon3/3, although the presence of an
      APOE epsilon4 allele was associated with an increased risk of dementia (odd ratio
      6.17; 95% confidence interval: 1.15-33.15), but not to an earlier age of onset.
      Complex segregation analysis showed that the best model fitting the data was that
      of a major gene (dominant) with a gene frequency close to 3% in this population.
      Simulation analysis predicted an average logarithm of odds (LOD) of 2.2 at =
      0.05. These four families, which seem to be part of a common extended pedigree
      originated by a founder arriving in this region in the 18th century, represent an
      autosomal dominant late-onset familial Alzheimer's disease not linked to
      previously known genetic loci. The simulation analysis suggests that it will be
      feasible to locate a novel responsible gene in these kindred.

PMID- 15843425
TI  - Understanding resolution of deliberate self harm: qualitative interview study of
      patients' experiences.
AB  - OBJECTIVE: To explore the accounts of those with a history of deliberate self
      harm but who no longer do so, to understand how they perceive this resolution and
      to identify potential implications for provision of health services. DESIGN:
      Qualitative in-depth interview study. SETTING: Interviews in a community setting.
      PARTICIPANTS: 20 participants selected from a representative cohort identified in
      1997 after an episode of deliberate self poisoning that resulted in hospital
      treatment. Participants were included if they had no further episodes for at
      least two years before interview. RESULTS: We identified three recurrent themes:
      the resolution of adolescent distress; the recognition of the role of alcohol as
      a precipitating and maintaining factor in self harm; and the understanding of
      deliberate self harm as a symptom of untreated or unrecognised illness.
      CONCLUSION: Patients with a history of deliberate self harm who no longer harm
      themselves talk about their experiences in terms of lack of control over their
      lives, either through alcohol dependence, untreated depression, or, in
      adolescents, uncertainty within their family relationships. Hospital management
      of deliberate self harm has a role in the identification and treatment of
      depression and alcohol misuse, although in adolescents such interventions may be
      less appropriate.

PMID- 15843426
TI  - Analysis of the distribution of time that patients spend in emergency
      departments.

PMID- 15843427
TI  - Patients' and health professionals' views on primary care for people with serious
      mental illness: focus group study.
AB  - OBJECTIVE: To explore the experience of providing and receiving primary care from
      the perspectives of primary care health professionals and patients with serious
      mental illness respectively. DESIGN: Qualitative study consisting of six patient
      groups, six health professional groups, and six combined focus groups. SETTING:
      Six primary care trusts in the West Midlands. PARTICIPANTS: Forty five patients
      with serious mental illness, 39 general practitioners (GPs), and eight practice
      nurses. RESULTS: Most health professionals felt that the care of people with
      serious mental illness was too specialised for primary care. However, most
      patients viewed primary care as the cornerstone of their health care and
      preferred to consult their own GP, who listened and was willing to learn, rather
      than be referred to a different GP with specific mental health knowledge. Swift
      access was important to patients, with barriers created by the effects of the
      illness and the noisy or crowded waiting area. Some patients described how they
      exaggerated symptoms ("acted up") to negotiate an urgent appointment, a strategy
      that was also employed by some GPs to facilitate admission to secondary care.
      Most participants felt that structured reviews of care had value. However,
      whereas health professionals perceived serious mental illness as a lifelong
      condition, patients emphasised the importance of optimism in treatment and hope
      for recovery. CONCLUSIONS: Primary care is of central importance to people with
      serious mental illness. The challenge for health professionals and patients is to
      create a system in which patients can see a health professional when they want to
      without needing to exaggerate their symptoms. The importance that patients attach
      to optimism in treatment, continuity of care, and listening skills compared with
      specific mental health knowledge should encourage health professionals in primary
      care to play a greater role in the care of patients with serious mental illness.

PMID- 15843428
TI  - Dedifferentiation of adult human myoblasts induced by ciliary neurotrophic factor
      in vitro.
AB  - Ciliary neurotrophic factor (CNTF) is primarily known for its important cellular
      effects within the nervous system. However, recent studies indicate that its
      receptor can be highly expressed in denervated skeletal muscle. Here, we
      investigated the direct effect of CNTF on skeletal myoblasts of adult human.
      Surprisingly, we found that CNTF induced the myogenic lineage-committed myoblasts
      at a clonal level to dedifferentiate into multipotent progenitor cells--they not
      only could proliferate for over 20 passages with the expression absence of
      myogenic specific factors Myf5 and MyoD, but they were also capable of
      differentiating into new phenotypes, mainly neurons, glial cells, smooth muscle
      cells, and adipocytes. These "progenitor cells" retained their myogenic memory
      and were capable of redifferentiating into myotubes. Furthermore, CNTF could
      activate the p44/p42 MAPK and down-regulate the expression of myogenic regulatory
      factors (MRFs). Finally, PD98059, a specific inhibitor of p44/p42 MAPK pathway,
      was able to abolish the effects of CNTF on both myoblast fate and MRF expression.
      Our results demonstrate the myogenic lineage-committed human myoblasts can
      dedifferentiate at a clonal level and CNTF is a novel regulator of skeletal
      myoblast dedifferentiation via p44/p42 MAPK pathway.

PMID- 15843429
TI  - Functional analysis of human microtubule-based motor proteins, the kinesins and
      dyneins, in mitosis/cytokinesis using RNA interference.
AB  - Microtubule (MT)-based motor proteins, kinesins and dyneins, play important roles
      in multiple cellular processes including cell division. In this study, we
      describe the generation and use of an Escherichia coli RNase III-prepared human
      kinesin/dynein esiRNA library to systematically analyze the functions of all
      human kinesin/dynein MT motor proteins. Our results indicate that at least 12
      kinesins are involved in mitosis and cytokinesis. Eg5 (a member of the kinesin-5
      family), Kif2A (a member of the kinesin-13 family), and KifC1 (a member of the
      kinesin-14 family) are crucial for spindle formation; KifC1, MCAK (a member of
      the kinesin-13 family), CENP-E (a member of the kinesin-7 family), Kif14 (a
      member of the kinesin-3 family), Kif18 (a member of the kinesin-8 family), and
      Kid (a member of the kinesin-10 family) are required for chromosome congression
      and alignment; Kif4A and Kif4B (members of the kinesin-4 family) have roles in
      anaphase spindle dynamics; and Kif4A, Kif4B, MKLP1, and MKLP2 (members of the
      kinesin-6 family) are essential for cytokinesis. Using immunofluorescence
      analysis, time-lapse microscopy, and rescue experiments, we investigate the roles
      of these 12 kinesins in detail.

PMID- 15843431
TI  - Chromosomal storage of the RNA-editing enzyme ADAR1 in Xenopus oocytes.
AB  - ADARs (adenosine deaminases that act on RNA) are RNA-editing enzymes that convert
      adenosines to inosines in structured or double-stranded RNAs. Expression and
      intracellular distribution of ADAR1 is controlled by a plethora of mechanisms
      suggesting that enzyme activity has to be tightly regulated. Mammalian ADAR1 is a
      shuttling protein, whereas Xenopus ADAR1 is exclusively nuclear. In oocytes,
      Xenopus ADAR1 associates with most nascent transcripts but is strongly enriched
      at a specific site on chromosome 3, termed the special loop. Enrichment at this
      site requires the presence of RNAs but is independent of ongoing transcription.
      Here we show that RNAs transcribed elsewhere in the genome accumulate at the
      special loop even in the absence of transcription. In situ hybridization
      experiments, however, indicate the absence of known editing substrates from this
      site. In the absence of transcription also other RNA binding and processing
      factors accumulate at the special loop, suggesting that ADAR1 is stored or
      assembled at the special loop in an RNA-containing complex. Nuclear injection of
      RNAs providing binding sites for ADAR1 dissociates the enzyme from the special
      loop, supporting the notion that the special loop represents a site where ADAR1
      is stored, possibly for later use during development.

PMID- 15843430
TI  - Genetic analysis of lysosomal trafficking in Caenorhabditis elegans.
AB  - The intestinal cells of Caenorhabditis elegans embryos contain prominent,
      birefringent gut granules that we show are lysosome-related organelles. Gut
      granules are labeled by lysosomal markers, and their formation is disrupted in
      embryos depleted of AP-3 subunits, VPS-16, and VPS-41. We define a class of gut
      granule loss (glo) mutants that are defective in gut granule biogenesis. We show
      that the glo-1 gene encodes a predicted Rab GTPase that localizes to lysosome
      related gut granules in the intestine and that glo-4 encodes a possible GLO-1
      guanine nucleotide exchange factor. These and other glo genes are homologous to
      genes implicated in the biogenesis of specialized, lysosome-related organelles
      such as melanosomes in mammals and pigment granules in Drosophila. The glo
      mutants thus provide a simple model system for the analysis of lysosome-related
      organelle biogenesis in animal cells.

PMID- 15843432
TI  - Lamin A/C-dependent localization of Nesprin-2, a giant scaffolder at the nuclear
      envelope.
AB  - The vertebrate proteins Nesprin-1 and Nesprin-2 (also referred to as Enaptin and
      NUANCE) together with ANC-1 of Caenorhabditis elegans and MSP-300 of Drosophila
      melanogaster belong to a novel family of alpha-actinin type actin-binding
      proteins residing at the nuclear membrane. Using biochemical techniques, we
      demonstrate that Nesprin-2 binds directly to emerin and the C-terminal common
      region of lamin A/C. Selective disruption of the lamin A/C network in COS7 cells,
      using a dominant negative lamin B mutant, resulted in the redistribution of
      Nesprin-2. Furthermore, using lamin A/C knockout fibroblasts we show that lamin
      A/C is necessary for the nuclear envelope localization of Nesprin-2. In normal
      skin where lamin A/C is differentially expressed, strong Nesprin-2 expression was
      found in all epidermal layers, including the basal layer where only lamin C is
      present. This indicates that lamin C is sufficient for proper Nesprin-2
      localization at the nuclear envelope. Expression of dominant negative Nesprin-2
      constructs and knockdown studies in COS7 cells revealed that the presence of
      Nesprin-2 at the nuclear envelope is necessary for the proper localization of
      emerin. Our data imply a scaffolding function of Nesprin-2 at the nuclear
      membrane and suggest a potential involvement of this multi-isomeric protein in
      human disease.

PMID- 15843434
TI  - Mechanical strain opens connexin 43 hemichannels in osteocytes: a novel mechanism
      for the release of prostaglandin.
AB  - Mechanosensing bone osteocytes express large amounts of connexin (Cx)43, the
      component of gap junctions; yet, gap junctions are only active at the small tips
      of their dendritic processes, suggesting another function for Cx43. Both primary
      osteocytes and the osteocyte-like MLO-Y4 cells respond to fluid flow shear stress
      by releasing intracellular prostaglandin E2 (PGE2). Cells plated at lower
      densities release more PGE2 than cells plated at higher densities. This response
      was significantly reduced by antisense to Cx43 and by the gap junction and
      hemichannel inhibitors 18 beta-glycyrrhetinic acid and carbenoxolone, even in
      cells without physical contact, suggesting the involvement of Cx43-hemichannels.
      Inhibitors of other channels, such as the purinergic receptor P2X7 and the
      prostaglandin transporter PGT, had no effect on PGE2 release. Cell surface
      biotinylation analysis showed that surface expression of Cx43 was increased by
      shear stress. Together, these results suggest fluid flow shear stress induces the
      translocation of Cx43 to the membrane surface and that unapposed hemichannels
      formed by Cx43 serve as a novel portal for the release of PGE2 in response to
      mechanical strain.

PMID- 15843433
TI  - Protein kinase A gating of a pseudopodial-located RhoA/ROCK/p38/NHE1 signal
      module regulates invasion in breast cancer cell lines.
AB  - Metastasis results from a sequence of selective events often involving
      interactions with elements of the tumor-specific physiological microenvironment.
      The low-serum component of this microenvironment confers increased motility and
      invasion in breast cancer cells by activating the Na+/H+ exchanger isoform 1
      (NHE1). The present study was undertaken to characterize the signal transduction
      mechanisms underlying this serum deprivation-dependent activation of both the
      NHE1 and the concomitant invasive characteristics such as leading edge
      pseudopodia development and penetration of matrigel in breast cancer cell lines
      representing different stages of metastatic progression. Using pharmacological
      and genetic manipulation together with transport and kinase activity assays, we
      observe that the activation of the NHE1 and subsequent invasion by serum
      deprivation in metastatic human breast cells is coordinated by a sequential
      RhoA/p160ROCK/p38MAPK signaling pathway gated by direct protein kinase A
      phosphorylation and inhibition of RhoA. Fluorescence resonance energy transfer
      imaging of RhoA activity and immunofluorescence analysis of phospho-RhoA and NHE1
      show that serum deprivation dynamically remodels the cell, forming long, leading
      edge pseudopodia and that this signal module is preferentially compartmentalized
      in these leading edge pseudopodia, suggesting a tight topographic relation of the
      signaling module to an invasion-specific cell structure.

PMID- 15843436
TI  - Peptide-loaded chimeric influenza virosomes for efficient in vivo induction of
      cytotoxic T cells.
AB  - Virus-specific CD8(+) T cells are thought to play an important role in resolving
      acute hepatitis C virus (HCV) infection as viral clearance has been associated
      with a strong and sustained CD8(+) T cell response. During the chronic state of
      HCV infection virus-specific T cells have a low frequency and a reduced
      responsiveness. Based on this, a therapeutic vaccine increasing the frequency of
      specific T cells is a promising alternative for the treatment of chronic HCV
      infection. We improved an existing vaccine platform based on immunopotentiating
      reconstituted influenza virosomes (IRIVs) for efficient delivery of peptide
      epitopes to the MHC class I antigen presentation pathway. IRIVs are
      proteoliposomes composed of phospholipids and influenza surface glycoproteins.
      Due to their fusogenic activity, IRIVs are able to deliver encapsulated
      macromolecules, e.g. peptides to immunocompetent cells. We developed a novel
      method based on chimeric virosomes [chimeric immunopotentiating reconstituted
      influenza virosomes (CIRIVs)] combining the high peptide-encapsulation capacity
      of liposomes and the fusion activity of virosomes. This new approach resulted in
      a 30-fold increase of the amount of incorporated soluble peptide compared with
      current preparation methods. To study the immunogenicity of chimeric virosomes
      HLA-A2.1 transgenic mice were immunized with CIRIVs containing the HCV Core132
      peptide. Core132-CIRIVs efficiently induced specific cytotoxic and IFNgamma
      producing T cells already with low peptide doses. Vaccine formulations, which
      include combinations of different HCV-derived CTL epitopes could be used to
      induce not only a strong but also a multi-specific CTL response, making them
      potential candidates for therapeutic and maybe prophylactic T cell vaccines in
      humans.

PMID- 15843435
TI  - G protein-coupled receptor kinase 2-mediated phosphorylation of ezrin is required
      for G protein-coupled receptor-dependent reorganization of the actin
      cytoskeleton.
AB  - G protein-coupled receptor kinase 2 (GRK2) phosphorylates and desensitizes
      activated G protein-coupled receptors (GPCRs). Here, we identify ezrin as a novel
      non-GPCR substrate of GRK2. GRK2 phosphorylates glutathione S-transferase (GST)
      ezrin, but not an ezrin fusion protein lacking threonine 567 (T567), in vitro.
      These results suggest that T567, the regulatory phosphorylation site responsible
      for maintaining ezrin in its active conformation, represents the principle site
      of GRK2-mediated phosphorylation. Two lines of evidence indicate that GRK2
      mediated ezrin-radixinmoesin (ERM) phosphorylation serves to link GPCR activation
      to cytoskeletal reorganization. First, in Hep2 cells muscarinic M1 receptor
      (M1MR) activation causes membrane ruffling. This ruffling response is ERM
      dependent and is accompanied by ERM phosphorylation. Inhibition of GRK2, but not
      rho kinase or protein kinase C, prevents ERM phosphorylation and membrane
      ruffling. Second, agonist-induced internalization of the beta2-adrenergic
      receptor (beta2AR) and M1MR is accompanied by ERM phosphorylation and
      localization of phosphorylated ERM to receptor-containing endocytic vesicles. The
      colocalization of internalized beta2AR and phosphorylated ERM is not dependent on
      Na+/H+ exchanger regulatory factor binding to the beta2AR. Inhibition of ezrin
      function impedes beta2AR internalization, further linking GPCR activation, GRK
      activity, and ezrin function. Overall, our results suggest that GRK2 serves not
      only to attenuate but also to transduce GPCR-mediated signals.

PMID- 15843437
TI  - Evidence that the COOH terminus of human presenilin 1 is located in
      extracytoplasmic space.
AB  - The polytopic membrane protein presenilin 1 (PS1) is a component of the gamma
      secretase complex that is responsible for the intramembranous cleavage of several
      type I transmembrane proteins, including the beta-amyloid precursor protein
      (APP). Mutations of PS1, apparently leading to aberrant processing of APP, have
      been genetically linked to early-onset familial Alzheimer's disease. PS1 contains
      10 hydrophobic regions (HRs) sufficiently long to be alpha-helical membrane
      spanning segments. Most topology models for PS1 place its COOH terminal
      approximately 40 amino acids, which include HR 10, in the cytosolic space.
      However, several recent observations suggest that HR 10 may be integrated into
      the membrane and involved in the interaction between PS1 and APP. We have applied
      three independent methodologies to investigate the location of HR 10 and the
      extreme COOH terminus of PS1. The results from these methods indicate that HR 10
      spans the membrane and that the COOH terminal amino acids of PS1 lie in the
      extracytoplasmic space.

PMID- 15843438
TI  - K+ channel KVLQT1 located in the basolateral membrane of distal colonic
      epithelium is not essential for activating Cl- secretion.
AB  - The cellular mechanism for Cl(-) and K(+) secretion in the colonic epithelium
      requires K(+) channels in the basolateral and apical membranes. Colonic mucosa
      from guinea pig and rat were fixed, sectioned, and then probed with antibodies to
      the K(+) channel proteins K(V)LQT1 (Kcnq1) and minK-related peptide 2 (MiRP2,
      Kcne3). Immunofluorescence labeling for Kcnq1 was most prominent in the lateral
      membrane of crypt cells in rat colon. The guinea pig distal colon had distinct
      lateral membrane immunoreactivity for Kcnq1 in crypt and surface cells. In
      addition, Kcne3, an auxiliary subunit for Kcnq1, was detected in the lateral
      membrane of crypt and surface cells in guinea pig distal colon. Transepithelial
      short-circuit current (I(sc)) and transepithelial conductance (G(t)) were
      measured for colonic mucosa during secretory activation by epinephrine (EPI),
      prostaglandin E(2) (PGE(2)), and carbachol (CCh). HMR1556 (10 microM), an
      inhibitor of Kcnq1 channels (Gerlach U, Brendel J, Lang HJ, Paulus EF, Weidmann
      K, Bruggemann A, Busch A, Suessbrich H, Bleich M, and Greger R. J Med Chem 44:
      3831-3837, 2001), partially (approximately 50%) inhibited Cl(-) secretory I(sc)
      and G(t) activated by PGE(2) and CCh in rat colon with an IC(50) of 55 nM, but in
      guinea pig distal colon Cl(-) secretory I(sc) and G(t) were unaltered. EPI
      activated K(+)-secretory I(sc) and G(t) also were essentially unaltered by
      HMR1556 in both rat and guinea pig colon. Although immunofluorescence labeling
      with a Kcnq1 antibody supported the basolateral membrane presence in colonic
      epithelium of the guinea pig as well as the rat, the Kcnq1 K(+) channel is not an
      essential component for producing Cl(-) secretion. Other K(+) channels present in
      the basolateral membrane presumably must also contribute directly to the K(+)
      conductance necessary for K(+) exit during activation of Cl(-) secretion in the
      colonic mucosa.

PMID- 15843439
TI  - Desensitization of canonical transient receptor potential channel 5 by protein
      kinase C.
AB  - The classic type of transient receptor potential channel (TRPC) is a molecular
      candidate for Ca(2+)-permeable cation channel in mammalian cells. TRPC5 is
      desensitized rapidly after activation by G protein-coupled receptor. Herein we
      report our investigation into the desensitization of mTRPC5 and localization of
      the molecular determinants of this desensitization using mutagenesis. TRPC5 was
      initially activated by muscarinic stimulation using 100 microM carbachol (CCh)
      and then decayed rapidly even in the presence of CCh (desensitization). Increased
      EGTA or omission of MgATP in the pipette solution slowed the rate of this
      desensitization. The protein kinase C (PKC) inhibitors, 1 microM chelerythrine,
      100 nM GF109203X, or PKC peptide inhibitor (19-36), inhibited this
      desensitization of TRPC5 activated by 100 microM CCh. When TRPC5 current was
      activated by intracellular GTPgammaS, PKC inhibitors prevented TRPC5
      desensitization and the mutation of TRPC5 T972 to alanine slowed the
      desensitization process dramatically. We conclude that the desensitization of
      TRPC5 occurs via PKC phosphorylation and suggest that threonine at residue 972 of
      mouse TRPC5 might be required for its phosphorylation by PKC.

PMID- 15843440
TI  - NKCC1 and NHE1 are abundantly expressed in the basolateral plasma membrane of
      secretory coil cells in rat, mouse, and human sweat glands.
AB  - In isolated sweat glands, bumetanide inhibits sweat secretion. The mRNA encoding
      bumetanide-sensitive Na(+)-K(+)-Cl(-) cotransporter (NKCC) isoform 1 (NKCC1) has
      been detected in sweat glands; however, the cellular and subcellular protein
      localization is unknown. Na(+)/H(+) exchanger (NHE) isoform 1 (NHE1) protein has
      been localized to both the duct and secretory coil of human sweat duct; however,
      the NHE1 abundance in the duct was not compared with that in the secretory coil.
      The aim of this study was to test whether mRNA encoding NKCC1, NKCC2, and Na(+)
      coupled acid-base transporters and the corresponding proteins are expressed in
      rodent sweat glands and, if expressed, to determine the cellular and subcellular
      localization in rat, mouse, and human eccrine sweat glands. NKCC1 mRNA was
      demonstrated in rat palmar tissue, including sweat glands, using RT-PCR, whereas
      NKCC2 mRNA was absent. Also, NHE1 mRNA was demonstrated in rat palmar tissue,
      whereas NHE2, NHE3, NHE4, electrogenic Na(+)-HCO(3)(-) cotransporter 1 NBCe1,
      NBCe2, electroneutral Na(+)-HCO(3)(-) cotransporter NBCn1, and Na(+)-dependent
      Cl(-)/HCO(3)(-) exchanger NCBE mRNA were not detected. The expression of NKCC1
      and NHE1 proteins was confirmed in rat palmar skin by immunoblotting, whereas
      NKCC2, NHE2, and NHE3 proteins were not detected. Immunohistochemistry was
      performed using sections from rat, mouse, and human palmar tissue.
      Immunoperoxidase labeling revealed abundant expression of NKCC1 and NHE1 in the
      basolateral domain of secretory coils of rat, mouse, and human sweat glands and
      low expression was found in the coiled part of the ducts. In contrast, NKCC1 and
      NHE1 labeling was absent from rat, mouse, and human epidermis. Immunoelectron
      microscopy demonstrated abundant NKCC1 and NHE1 labeling of the basolateral
      plasma membrane of mouse sweat glands, with no labeling of the apical plasma
      membranes or intracellular structures. The basolateral NKCC1 of the secretory
      coils of sweat glands would most likely account for the observed bumetanide
      sensitive NaCl secretion in the secretory coils, and the basolateral NHE1 is
      likely to be involved in Na(+)-coupled acid-base transport.

PMID- 15843441
TI  - Cd2+-induced swelling-contraction dynamics in isolated kidney cortex
      mitochondria: role of Ca2+ uniporter, K+ cycling, and protonmotive force.
AB  - The nephrotoxic metal Cd(2+) causes mitochondrial damage and apoptosis of kidney
      proximal tubule cells. A K(+) cycle involving a K(+) uniporter and a K(+)/H(+)
      exchanger in the inner mitochondrial membrane (IMM) is thought to contribute to
      the maintenance of the structural and functional integrity of mitochondria. In
      the present study, we have investigated the effect of Cd(2+) on K(+) cycling in
      rat kidney cortex mitochondria. Cd(2+) (EC(50) approximately 19 microM) induced
      swelling of nonenergized mitochondria suspended in isotonic salt solutions
      according to the sequence KCl = NaCl > LiCl >> choline chloride. Cd(2+)-induced
      swelling of energized mitochondria had a similar EC(50) value and showed the same
      cation dependence but was followed by a spontaneous contraction. Mitochondrial
      Ca(2+) uniporter (MCU) blockers, but not permeability transition pore inhibitors,
      abolished swelling, suggesting the need for Cd(2+) influx through the MCU for
      swelling to occur. Complete loss of mitochondrial membrane potential
      (DeltaPsi(m)) induced by K(+) influx did not prevent contraction, but addition of
      the K(+)/H(+) exchanger blocker, quinine (1 mM), or the electroneutral
      protonophore nigericin (0.4 microM), abolished contraction, suggesting the
      mitochondrial pH gradient (DeltapH(m)) driving contraction. Accordingly, a
      quinine-sensitive partial dissipation of DeltapH(m) was coincident with the
      swelling-contraction phase. The data indicate that Cd(2+) enters the matrix
      through the MCU to activate a K(+) cycle. Initial K(+) load via a Cd(2+)
      activated K(+) uniporter in the IMM causes osmotic swelling and breakdown of
      DeltaPsi(m) and triggers quinine-sensitive K(+)/H(+) exchange and contraction.
      Thus Cd(2+)-induced activation of a K(+) cycle contributes to the dissipation of
      the mitochondrial protonmotive force.

PMID- 15843442
TI  - Constitutive secretion of serum albumin requires reversible protein tyrosine
      phosphorylation events in trans-Golgi.
AB  - Serum albumin secretion from rat hepatocytes proceeds via the constitutive
      pathway. Although much is known about the role of protein tyrosine
      phosphorylation in regulated secretion, nothing is known about its function in
      the constitutive process. Here we show that albumin secretion is inhibited by the
      tyrosine kinase inhibitor genistein but relatively insensitive to subtype
      selective inhibitors or treatments. Secretion is also blocked in a
      physiologically identical manner by the tyrosine phosphatase inhibitors
      pervanadate and bisperoxo(1,10-phenanthroline)-oxovanadate. Inhibition of either
      the kinase(s) or phosphatase(s) leads to the accumulation of albumin between the
      trans-Golgi and the plasma membrane, whereas the immediate precursor proalbumin
      builds up in a proximal compartment. The trans-Golgi marker TGN38 is rapidly
      dispersed under conditions that inhibit tyrosine phosphatase action, whereas the
      distribution of the cis-Golgi marker GM130 is insensitive to genistein or
      pervanadate. By using a specifically reactive biotinylation probe, we detected
      protein tyrosine phosphatases in highly purified rat liver Golgi membranes. These
      membranes also contain both endogenous tyrosine kinases and their substrates,
      indicating that enzymes and substrates for reversible tyrosine phosphorylation
      are normal membrane-resident components of this trafficking compartment. In the
      absence of perturbation of actin filaments and microtubules, we conclude that
      reversible protein tyrosine phosphorylation in the trans-Golgi network is
      essential for albumin secretion and propose that the constitutive secretion of
      albumin is in fact a regulated process.

PMID- 15843443
TI  - Role of SGK1 in nitric oxide inhibition of ENaC in Na+-transporting epithelia.
AB  - Several studies have shown that nitric oxide (NO) inhibits Na(+) transport in
      renal and alveolar monolayers. However, the mechanisms by which NO alters
      epithelial Na(+) channel (ENaC) activity is unclear. Therefore, we examined the
      effect of applying the NO donor drug l-propanamine 3,2-hydroxy-2-nitroso-1
      propylhidrazino (PAPA-NONOate) to cultured renal epithelial cells. A6 and M1
      cells were maintained on permeable supports in medium containing 1.5 microM
      dexamethasone and 10% bovine serum. After 1.5 microM PAPA-NONOate was applied,
      amiloride-sensitive short-circuit current measurements decreased 29% in A6 cells
      and 44% in M1 cells. This differed significantly from the 3% and 19% decreases in
      A6 and M1 cells, respectively, treated with control donor compound (P < 0.0005).
      Subsequent application of PAPA-NONOate to amiloride-treated control (no NONOate)
      A6 and M1 cells did not further decrease transepithelial current. In single
      channel patch-clamp studies, NONOate significantly decreased ENaC open
      probability (P(o)) from 0.186 +/- 0.043 to 0.045 +/- 0.009 (n = 7; P < 0.05)
      without changing the unitary current. We also showed that aldosterone
      significantly decreased NO production in primary cultures of alveolar type II
      (ATII) epithelial cells. Because inducible nitric oxide synthase (iNOS)
      coimmunoprecipitated with the serum- and glucocorticoid-inducible kinase (SGK1)
      and both proteins colocalized in the cytoplasm (as shown in our studies in mouse
      ATII cells), SGK1 may also be important in regulating NO production in the
      alveolar epithelium. Our study also identified iNOS as a novel SGK1
      phosphorylated protein (at S733 and S903 residues in miNOS) suggesting that one
      way in which SGK1 could increase Na(+) transport is by altering iNOS production
      of NO.

PMID- 15843444
TI  - Three year joint space narrowing predicts long term incidence of knee surgery in
      patients with osteoarthritis: an eight year prospective follow up study.
AB  - OBJECTIVE: To assess the clinical relevance of mean and minimum femorotibial
      joint space narrowing (JSN) for predicting future osteoarthritis related surgery
      in patients with knee osteoarthritis. METHODS: 126 subjects with primary knee
      osteoarthritis were followed prospectively for a mean eight years. Minimum and
      mean joint space width (JSW) were assessed from standard x rays at baseline and
      after a follow up of three years. The rate of knee osteoarthritis related surgery
      was recorded for the following five years. RESULTS: After a mean follow up of
      eight years, 16 patients (12.7%) had received osteoarthritis related joint
      surgery. The areas under the curves (AUC) resulting from the receiver operating
      characteristic curve analyses for predicting osteoarthritis surgery were 0.73
      (p=0.006) for minimum JSN and 0.55 (p=0.54) for mean JSN. The cut off for minimum
      JSN maximising sensitivity and specificity for predicting future surgery was a
      change of 0.7 mm or more in minimum joint space width over a period of three
      years. However, no meaningful differences were observed for cut off values
      between 0.5 and 0.8 mm The relative risk (adjusted for age, body mass index,
      baseline symptoms, and baseline JSW) of experiencing osteoarthritis related
      surgery during the eight year of follow up was 5.15 (95% confidence interval,
      1.70 to 15.60) (p=0.004) in patients with a minimum joint space narrowing of 0.7
      mm or more during the first three years of the study. CONCLUSIONS: A cut off of
      0.5 to 0.8 mm in minimum JSN, measured on standard x rays, reflects a clinically
      relevant progression in patients with knee osteoarthritis.

PMID- 15843445
TI  - Do steroids increase lymphoma risk? A case-control study of lymphoma risk in
      polymyalgia rheumatica/giant cell arteritis.
AB  - BACKGROUND: Recent studies indicate increased risks of malignant lymphomas among
      individuals treated with corticosteroids, but have not taken into account the
      underlying reasons for steroid use, so the increased risks might be attributable
      to the underlying disease or concomitant treatments other than steroids.
      Polymyalgia rheumatica (PMR) and temporal arteritis (giant cell arteritis, GCA)
      are common inflammatory conditions treated with steroids as single
      immunosuppressive therapy, but data on lymphoma risk in GCA/PMR are limited.
      OBJECTIVE: To assess the risk of lymphoma associated with steroid treatment of
      GCA/PMR. METHODS: The association between GCA/PMR and malignant lymphomas
      (overall, and separately for non-Hodgkin lymphoma, Hodgkin lymphoma, and chronic
      lymphatic leukaemia) was examined in a nationwide, population based, case-control
      study of 42,676 lymphoma cases and 78,487 matched population controls, using
      prospectively recorded data on lymphomas from the Swedish cancer register 1964
      2000 and data on pre-lymphoma hospital admissions for GCA/PMR from the Swedish
      inpatient register 1964-2000. Odds ratios (OR) associated with a pre-lymphoma
      hospital admission for GCA/PMR were calculated using conditional logistic
      regression. RESULTS: 153 lymphoma cases and 345 population controls had a history
      of GCA/PMR, resulting in an overall OR for malignant lymphomas of 0.81 (95%
      confidence interval, 0.67 to 0.98). The OR varied little with lymphoma type, sex,
      age, and calendar period. The OR for GCA was 0.67 (0.48 to 0.98) and for PMR,
      0.83 (0.67 to 1.04). CONCLUSIONS: Treated GCA is not associated with increased
      lymphoma risks, which suggests that even at considerable cumulative doses,
      steroids may not appreciably increase lymphoma risk.

PMID- 15843446
TI  - Patellofemoral osteoarthritis coexistent with tibiofemoral osteoarthritis in a
      meniscectomy population.
AB  - OBJECTIVES: To evaluate the frequency of patellofemoral osteoarthritis and its
      relevance to symptoms and function in a meniscectomy population. METHODS: 317
      patients with no cruciate ligament injury were evaluated (mean (SD) age, 54 (11)
      years). They had undergone meniscal resection 15 to 22 years earlier (follow up
      rate 70%). Standing tibiofemoral and skyline patellofemoral radiographs were
      graded according to the OARSI atlas. The Knee Injury and Osteoarthritis Outcome
      Score (KOOS) was used to quantify symptoms and function. Controls were 68
      unoperated subjects identified from national population records. RESULTS:
      Patellofemoral osteoarthritis (isolated or coexisting with tibiofemoral
      osteoarthritis) was present in 66 of 317 index knees (21%) and 21 of 263
      unoperated contralateral knees (8%, p<0.001). In 57/66 (86%) of these index
      knees, tibiofemoral osteoarthritis was present (mixed osteoarthritis). In a model
      adjusted for age, sex, and body mass index, the odds ratio for patellofemoral
      osteoarthritis (alone or in combination with tibiofemoral osteoarthritis) was 2.6
      (95% confidence interval, 1.1 to 6.6) after medial meniscectomy and 5.3 (1.9 to
      15.0) after lateral meniscectomy, using controls as the reference. Individuals
      with a mixed knee osteoarthritis pattern had more symptoms, lower function in
      sports and recreation, and worse knee related quality of life than subjects with
      isolated tibiofemoral osteoarthritis. CONCLUSIONS: Mixed patellofemoral and
      tibiofemoral osteoarthritis is common in a meniscectomy population.
      Patellofemoral osteoarthritis is a contributing cause of knee symptoms and
      reduced knee related quality of life and is relevant to the management of knee
      complaints of this group of patients.

PMID- 15843447
TI  - Variations in performance characteristics of commercial enzyme immunoassay kits
      for detection of antineutrophil cytoplasmic antibodies: what is the optimal cut
      off?
AB  - BACKGROUND: Previous studies have shown considerable variation in diagnostic
      performance of enzyme linked immunosorbent assays (ELISAs) for measuring
      antineutrophil cytoplasmic antibodies (ANCA) specific for proteinase 3 (PR3) and
      myeloperoxidase (MPO). OBJECTIVE: To analyse the performance characteristics of
      different commercially available direct ANCA ELISA kits. METHODS: ELISA kits for
      detecting PR3-ANCA and MPO-ANCA from 11 manufacturers were evaluated. Serum
      samples were taken from patients with Wegener's granulomatosis (15), microscopic
      polyangiitis (15), other vasculitides (10), and controls (40). RESULTS: were
      compared with data obtained by indirect immunofluorescence (IFT). The diagnostic
      performance of the tests was analysed and compared by receiver operating
      characteristic (ROC) curve analysis.Results: Applying the manufacturers' cut off
      resulted in great variation in sensitivity of the commercial PR3-ANCA kits for
      diagnosing Wegener's granulomatosis (ranging from 13.3% to 66.7%), and of the MPO
      ANCA kits for diagnosing microscopic polyangiitis (ranging from 26.7% to 66.7%).
      Specificities were relatively constant (from 96.0% to 100%). IFT was superior to
      all ELISAs (C-ANCA for Wegener's granulomatosis: sensitivity 73.3%, specificity
      98%; P-ANCA for microscopic polyangiitis: sensitivity 86.7%, specificity 98%).
      The sensitivities of PR3-ANCA and MPO-ANCA ELISA kits were increased by lowering
      the cut off values. This reduced specificity but increased overall diagnostic
      performance. CONCLUSIONS: The low sensitivity of some commercial kits reflects
      the high cut off levels recommended rather than methodological problems with the
      assays. Comparative analyses using sera from well characterised patients may help
      identify optimum cut off levels of commercial ANCA ELISA tests, resulting in
      better comparability of results among assays from different manufacturers.

PMID- 15843448
TI  - Sustained durability and tolerability of etanercept in ankylosing spondylitis for
      96 weeks.
AB  - OBJECTIVE: To evaluate the continued safety and durability of clinical response
      in patients with ankylosing spondylitis receiving etanercept. METHODS: 277
      patients who had participated in a previous randomised, double blind, placebo
      controlled 24 week trial were eligible to continue in this open label extension
      study. All patients who enrolled in the open label extension (n = 257) received
      subcutaneous etanercept 25 mg twice weekly for up to 72 weeks, for a combined 96
      weeks of cumulative trial and open label experience. For the patients who had
      received etanercept for 24 weeks in the double blind trial, this represented
      almost 2 years of continuous etanercept treatment. RESULTS: Patients continuing
      etanercept treatment had a sustained response for almost 2 years, with 74%
      achieving an ASsessments in Ankylosing Spondylitis 20% (ASAS 20) response after
      96 weeks of etanercept treatment. Patients who had received placebo in the
      preceding double blind trial had similar responses, with 70% of patients
      attaining an ASAS 20 response after 24 weeks of etanercept treatment and 78%
      achieving an ASAS 20 response after 72 weeks. Improved spinal mobility was seen
      in both groups. Etanercept was well tolerated in patients treated for up to 96
      weeks. CONCLUSION: The subcutaneous administration of twice weekly doses of
      etanercept provided sustained durability of response in the improvement of signs
      and symptoms of ankylosing spondylitis for nearly 2 years.

PMID- 15843449
TI  - Changes of cartilage and bone markers after intra-articular glucocorticoid
      treatment with and without postinjection rest in patients with rheumatoid
      arthritis.
AB  - BACKGROUND: Joint immobilisation improves the therapeutic effect of intra
      articular glucocorticoid injection for knee synovitis. This may be due to
      retarded steroid resorption by immobilisation, a procedure that also could
      influence cartilage and bone metabolism. OBJECTIVE: To evaluate changes in
      cartilage and bone turnover after intra-articular glucocorticoid treatment for
      knee synovitis with and without postinjection rest. METHODS: 20 patients with
      rheumatoid arthritis and knee synovitis were randomised to 24 hour bed rest or to
      normal activity after intra-articular glucocorticoid treatment. Serum and urine
      markers of cartilage and bone turnover were studied for two weeks. Cartilage
      oligomeric matrix protein (COMP) was used as a marker of cartilage turnover,
      osteocalcin as marker of bone formation, and deoxipyridinoline (DPD) as marker of
      bone resorption. RESULTS: After the glucocorticoid injection COMP levels
      decreased in both groups (p<0.001), but significantly more in resting patients.
      Serum osteocalcin levels decreased significantly (p<0.001) without any difference
      between the groups. DPD was unchanged in both groups. CONCLUSIONS: Intra
      articular glucocorticoid treatment for knee synovitis reduced serum COMP, which
      suggests that such treatment may have a cartilage protective effect. The slightly
      larger decrease of serum COMP in the resting group may reflect a lower clearance
      of COMP from the joint cavity. Serum osteocalcin was temporarily reduced,
      indicating a reversible suppression of bone formation.

PMID- 15843450
TI  - Cardiovascular admissions and mortality in an inception cohort of patients with
      rheumatoid arthritis with onset in the 1980s and 1990s.
AB  - BACKGROUND: There is increased cardiovascular disease mortality in rheumatoid
      arthritis. This may reflect an increased prevalence of cardiovascular disease or
      an increased case fatality in patients with rheumatoid arthritis. OBJECTIVES: To
      examine whether rheumatoid patients with disease onset in the 1980s-1990s have
      increased mortality, and to compare cardiovascular admission rates in rheumatoid
      patients with those of the general population. METHODS: An inception cohort of
      1010 rheumatoid patients attending Stockport rheumatology clinics between 1981
      and 1996 was followed up to December 2002 through the Office for National
      Statistics. Standardised mortality ratios (SMR) were calculated for all-cause and
      cause specific mortality, using the population of Stockport as reference.
      Cardiovascular disease admission rates were ascertained for a subgroup of
      patients using national hospital episode statistics; standardised cardiovascular
      disease admission rates (SAR) and SMRs were calculated for this subgroup.
      RESULTS: 470 patients (48%) died during a median follow up of 11.4 years. All
      cause mortality was increased in men (SMR = 1.45 (95% confidence interval, 1.22
      to 1.71)) and women (SMR = 1.84 (1.64 to 2.05)), as was cardiovascular disease
      mortality in men (SMR = 1.36 (1.04 to 1.75) and women (SMR = 1.93 (1.65 to
      2.26)). No difference in cardiovascular disease admission rates was observed in
      men (SAR 1.20 (0.89 to 1.58) or women (SAR = 1.10 (0.88 to 1.36)), despite excess
      cardiovascular disease mortality in this subgroup. CONCLUSIONS: Patients with
      rheumatoid arthritis have reduced life expectancy and excess cardiovascular
      disease mortality. Nevertheless, standardised admission rates for cardiovascular
      disease were not raised. This suggests either that cardiovascular disease in
      rheumatoid arthritis has a higher case fatality than in the general population or
      that it often goes unrecognised before the fatal event.

PMID- 15843451
TI  - Type I interferon correlates with serological and clinical manifestations of SLE.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting
      multiple organ systems triggered by the production of autoantibodies. Previous
      clinical studies in humans and murine models suggest that type I interferons
      (IFNs) are important for the initiation and potentiation of SLE activity.
      METHODS: 65 consecutive patients with SLE were identified from the University of
      California, San Francisco Lupus Clinic with moderate-severe disease activity. 94
      serological samples were collected. Type I IFN levels and the ability of plasma
      to induce expression of several surface markers of dendritic cell maturation were
      measured. RESULTS: Type I IFN levels correlated with the presence of cutaneous
      manifestations, and there was a trend towards correlation with renal disease. No
      correlation was found between type I IFN levels and neurological disease. Type I
      IFN levels correlated positively with the SLEDAI score and anti-dsDNA levels and
      inversely with C3 levels. Interestingly, type I IFN levels were highest in
      African American patients. SLE plasma also induced the expression of MHC class I,
      CD38, and CD123 on monocytes, and was blocked by the addition of a monoclonal
      antibody to IFNAR1. CONCLUSIONS: The pathogenic role of type I IFN is suggested
      by the induction of cell surface markers for dendritic cell maturation. The
      potential therapeutic utility of antibodies directed to either type I IFN or
      IFNAR1/IFNAR2 may be of interest in further studies.

PMID- 15843452
TI  - Longitudinal analysis of citrullinated protein/peptide antibodies (anti-CP)
      during 5 year follow up in early rheumatoid arthritis: anti-CP status predicts
      worse disease activity and greater radiological progression.
AB  - OBJECTIVE: To study serum levels of citrullinated protein/peptide antibodies
      (anti-CP) during up to 5 years' follow up of patients with early rheumatoid
      arthritis (RA), and to relate serum levels to disease course and to treatments in
      clinical practice. METHODS: 279 patients with early RA were followed up with
      clinical investigations, radiographs, and measurement of anti-CP at baseline and
      after 3 months, 1, 2, 3, and 5 years. RESULTS: 160/279 (57.3%) patients were anti
      CP positive at the first visit (mean 5 months after first symptoms). During
      follow up only 11/279 (3.9%) of the patients changed their anti-CP status. Anti
      CP levels fell significantly during the first year, and this drop correlated with
      the extent of sulfasalazine treatment but not with other drugs or clinical
      indices. Anti-CP positive and negative patients had similar disease activities at
      baseline, but during follow up the anti-CP positive patients had worse clinical
      disease and greater radiological progression, despite at least equally intensive
      antirheumatic treatment. CONCLUSIONS: Anti-CP are stable during the first 5 years
      of RA, suggesting that events before rather than after onset of clinical
      manifestations of disease determine this phenotype. The presence of anti-CP at
      diagnosis predicts a less favourable disease course and greater radiological
      progression despite antirheumatic treatment, but subsequent changes in antibody
      levels do not reflect changes in disease activity. Taken together, these
      observations suggest that anti-CP positive RA is a distinct clinical and
      pathophysiological entity.

PMID- 15843453
TI  - Sports activities 5 years after total knee or hip arthroplasty: the Ulm
      Osteoarthritis Study.
AB  - OBJECTIVE: To analyse sports activities of patients with hip or knee
      osteoarthritis (OA) over lifetime, preoperatively, and 5 years after
      arthroplasty. METHODS: In a longitudinal four centre study, 809 consecutive
      patients with advanced OA of the hip (420) or the knee (389) joint under the age
      of 76 years who required total joint replacement were recruited. A completed
      questionnaire about sports activities at 5 year follow up was received from 636
      (79%) of the 809 patients. RESULTS: Although most patients with hip (97%) and
      knee (94%) OA had performed sports activities during their life, only 36% (hip
      patients) and 42% (knee patients) had maintained sports activities at the time of
      surgery. Five years postoperatively, the proportion of patients performing sports
      activities increased to 52% among patients with hip OA, but further declined to
      34% among those with knee OA. Accordingly, the proportion of patients with hip OA
      performing sports activities for more than 2 hours a week increased from 8 to
      14%, whereas this proportion decreased from 12 to 5% among patients with knee OA.
      Pain in the replaced joint was reported by 9% of patients with hip and by >16%
      with knee OA. CONCLUSION: Differences in pain 5 years after joint replacement may
      explain some of the difference of sports activities between patients with hip and
      knee OA. Reasons for reduction of sports activities may include the increasing
      age of the patients, their worries about an "artificial joint", and the advice of
      their surgeon to be cautious.

PMID- 15843455
TI  - Socioeconomic status and the risk of developing rheumatoid arthritis: results
      from the Swedish EIRA study.
AB  - OBJECTIVE: To study whether formal education and occupational class are
      associated with incidence of rheumatoid arthritis overall and with the incidence
      of the two major subgroups of rheumatoid arthritis-seropositive (RF+) and
      seronegative (RF-) disease. METHODS: 930 cases and 1126 controls participated in
      a population based case-control study using incident cases of rheumatoid
      arthritis, carried out in Sweden during the period May 1996 to June 2001. The
      relative risk (RR) of developing rheumatoid arthritis with 95% confidence
      interval (CI) was calculated for different levels of formal education compared
      with university degree and for different occupational classes compared with
      higher non-manual employees. RESULTS:  SUBJECTS: without a university degree had
      an increased risk of rheumatoid arthritis compared with those with a university
      degree (RR = 1.4 (95% CI, 1.2 to 1.8)). For manual employees, assistant and
      intermediate non-manual employees together, the risk of developing rheumatoid
      arthritis was about 20% more than for non-manual employees. These increased risks
      were more pronounced for RF+ than for RF- rheumatoid arthritis and were mainly
      confined to women. Smoking could not of its own explain the observed associations
      between risk of rheumatoid arthritis in different socioeconomic groups in Sweden.
      CONCLUSIONS: There was an association between high socioeconomic status and lower
      risk of rheumatoid arthritis in a population based investigation that was
      representative for the Swedish population. The study shows that as yet
      unexplained environmental or lifestyle factors, or both, influence the risk of
      rheumatoid arthritis, even in the relatively egalitarian Swedish society.

PMID- 15843454
TI  - Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and
      characteristics after exposure to tumour necrosis factor antagonists.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) are at increased risk of
      malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect
      of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics
      is unclear. OBJECTIVE: To assess expected rates and relative risks of
      haematopoietic malignancies, especially those associated with TNF antagonists, in
      large population based cohorts of patients with RA. METHODS: A population based
      cohort study was performed of patients with RA (one prevalent cohort (n =
      53,067), one incident cohort (n = 3703), and one TNF antagonist treated cohort
      1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register.
      Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients
      with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed.
      RESULTS: Study of almost 500 observed haematopoietic malignancies showed that
      prevalent and incident patients with RA were at increased risk of lymphoma (SIR =
      1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but
      not of myeloma. Patients with RA treated with TNF antagonists had a tripled
      lymphoma risk (SIR = 2.9) compared with the general population. After adjustment
      for sex, age, and disease duration, the lymphoma risk after exposure to TNF
      antagonists was no higher than in the other RA cohorts. Lymphomas associated with
      TNF antagonists had characteristics similar to those of other RA lymphomas.
      CONCLUSION: Overall, patients with RA are at equally increased risks for
      lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not
      have higher lymphoma risks than other patients with RA. Prolonged observation is
      needed to determine the long term effects of TNF antagonists on lymphoma risk.

PMID- 15843456
TI  - Performance of health status measures with a pen based personal digital
      assistant.
AB  - BACKGROUND: Increasing use of self reported health status in clinical practice
      and research, as well as patient appreciation of monitoring fluctuations of
      health over time, suggest a need for more frequent collection of data. Electronic
      use of health status measures in the follow up of patients is a possible way to
      achieve this. OBJECTIVE: To compare self reported health status measures in a
      personal digital assistant (PDA) version and a paper/pencil version for test
      retest reliability, agreement between scores, and feasibility. METHODS: 30
      patients with stable rheumatoid arthritis (mean age 61.6 years, range 49.8 to
      70.0; mean disease duration, 16.7 years; 63% female; 67% rheumatoid factor
      positive; 46.6% on disease modifying antirheumatic drugs) completed self reported
      health status measures (pain, fatigue, and global health on visual analogue
      scales (VAS), rheumatoid arthritis disease activity index, modified health
      assessment questionnaire, SF-36) in a conventional paper based questionnaire
      version and on a PDA (HP iPAQ, model h5450). Completion was repeated after five
      to seven days. RESULTS: Test-retest reliability was similar, as evaluated by the
      Bland-Altman approach, the coefficient of variation, and intraclass correlation
      coefficients. The scores showed acceptable agreement, but with a slight tendency
      to higher scores on VAS with the PDA than the paper/pencil version. No
      significant differences were seen for measures of feasibility (time to complete,
      satisfaction score), but 65.5% preferred PDA, 20.7% preferred paper, and 13.8%
      had no preference. CONCLUSIONS: The clinimetric performance of paper/pencil
      versions of self reported health status measures was similar to an electronic
      version, using an inexpensive PDA.

PMID- 15843457
TI  - ICF based comparison of disease specific instruments measuring physical
      functional ability in ankylosing spondylitis.
AB  - OBJECTIVES: To link validated and widely used instruments measuring physical
      functional ability in ankylosing spondylitis to the International Classification
      of Functioning, Disability, and Health (ICF) and to compare their contents, based
      on the results of the linking process. METHODS: The Bath Ankylosing Spondylitis
      Functional Index (BASFI), the Dougados Functional Index (DFI), the Health
      Assessment Questionnaire modified for the spondylarthropathies (HAQ-S), and the
      Revised Leeds Disability Questionnaire (RLDQ) were linked to the ICF separately
      by two trained health professionals according to 10 linkage rules. RESULTS: All
      concepts contained in the items of the selected instruments could be successfully
      linked to the ICF except for "illness" included in the HAQ-S. Altogether 55
      different ICF categories were linked. Seven belonged to "body functions", 43 to
      "activities and participation", and five to "environmental factors". The
      component "body structure" was not contained in any of the four instruments. Only
      two ICF categories were common to all selected questionnaires, but there was a
      high level of concordance on the concepts represented in them. However,
      especially in terms of "activities and participation", the emphasised aspects
      differed. CONCLUSIONS: The ICF provides an excellent common framework for the
      comparison of disease specific instruments for ankylosing spondylitis. For a
      future revision of the ICF, a specification of major limitations in patients with
      ankylosing spondylitis is suggested.

PMID- 15843458
TI  - Massive nitrogen loss from the Benguela upwelling system through anaerobic
      ammonium oxidation.
AB  - In many oceanic regions, growth of phytoplankton is nitrogen-limited because
      fixation of N2 cannot make up for the removal of fixed inorganic nitrogen (NH4+,
      NO2-, and NO3-) by anaerobic microbial processes. Globally, 30-50% of the total
      nitrogen loss occurs in oxygen-minimum zones (OMZs) and is commonly attributed to
      denitrification (reduction of nitrate to N2 by heterotrophic bacteria). Here, we
      show that instead, the anammox process (the anaerobic oxidation of ammonium by
      nitrite to yield N2) is mainly responsible for nitrogen loss in the OMZ waters of
      one of the most productive regions of the world ocean, the Benguela upwelling
      system. Our in situ experiments indicate that nitrate is not directly converted
      to N2 by heterotrophic denitrification in the suboxic zone. In the Benguela
      system, nutrient profiles, anammox rates, abundances of anammox cells, and
      specific biomarker lipids indicate that anammox bacteria are responsible for
      massive losses of fixed nitrogen. We have identified and directly linked anammox
      bacteria to the removal of fixed inorganic nitrogen in the OMZ waters of an open
      ocean setting. We hypothesize that anammox could also be responsible for
      substantial nitrogen loss from other OMZ waters of the ocean.

PMID- 15843459
TI  - Functionally distinct polymorphic sequences in the human genome that are targets
      for p53 transactivation.
AB  - The p53 tumor suppressor protein is a master regulatory transcription factor that
      coordinates cellular responses to DNA damage and cellular stress. Besides
      mutations in p53, or in proteins involved in the p53 response pathway, genetic
      variation in promoter response elements (REs) of p53 target genes is expected to
      alter biological responses to stress. To identify SNPs in p53 REs that may modify
      p53-controlled gene expression, we developed an approach that combines a custom
      bioinformatics search to identify candidate SNPs with functional yeast and
      mammalian cell assays to assess their effect on p53 transactivation. Among
      approximately 2 million human SNPs, we identified >200 that seem to disrupt
      functional p53 REs. Eight of these SNPs were evaluated in functional assays to
      determine both the activity of the putative RE and the impact of the candidate
      SNPs on transactivation. All eight candidate REs were functional, and in every
      case the SNP pair exhibited differential transactivation capacities.
      Additionally, six of the eight genes adjacent to these SNPs are induced by
      genotoxic stress or are activated directly by transfection with p53 cDNA. Thus,
      this strategy efficiently identifies SNPs that may differentially affect gene
      expression responses in the p53 regulatory pathway.

PMID- 15843460
TI  - A coherent framework for multiresolution analysis of biological networks with
      "memory": Ras pathway, cell cycle, and immune system.
AB  - Various biological processes exhibit characteristics that vary dramatically in
      response to different input conditions or changes in the history of the process
      itself. One of the examples studied here, the Ras-PKC-mitogen-activated protein
      kinase (MAPK) bistable pathway, follows two distinct dynamics (modes) depending
      on duration and strength of EGF stimulus. Similar examples are found in the
      behavior of the cell cycle and the immune system. A classification methodology,
      based on time-frequency analysis, was developed and tested on these systems to
      understand global behavior of biological processes. Contrary to most
      traditionally used statistical and spectral methods, our approach captures
      complex functional relations between parts of the systems in a simple way. The
      resulting algorithms are capable of analyzing and classifying sets of time-series
      data obtained from in vivo or in vitro experiments, or in silico simulation of
      biological processes. The method was found to be considerably stable under
      stochastic noise perturbation and, therefore, suitable for the analysis of real
      experimental data.

PMID- 15843461
TI  - Using independent open-to-closed transitions to simplify aggregated Markov models
      of ion channel gating kinetics.
AB  - Deducing plausible reaction schemes from single-channel current traces is time
      consuming and difficult. The goal is to find the simplest scheme that fits the
      data, but there are many ways to connect even a small number of states (>2
      million schemes with four open and four closed states). Many schemes make
      identical predictions. An exhaustive search over model space does not address the
      many equivalent schemes that will result. We have found a canonical form that can
      express all reaction schemes for binary channels. This form has the minimal
      number of rate constants for any rank (number of independent open-closed
      transitions), unlike other canonical forms such as the well established
      "uncoupled" scheme. Because all of the interconductance transitions in the new
      form are independent, we refer to it as the manifest interconductance rank (MIR)
      form. In the case of four open and four closed states, there are four MIR form
      schemes, corresponding to ranks 1-4. For many models proposed in the literature
      for specific ion channels, the equivalent MIR form has dramatically fewer links
      than the uncoupled form. By using the MIR form we prove that all rank 1
      topologies with a given number of open and closed states make identical
      predictions in steady state, thus narrowing the search space for simple models.
      Moreover, we prove that fitting to canonical form preserves detailed balance. We
      also propose an efficient hierarchical algorithm for searching for the simplest
      possible model consistent with a given data set.

PMID- 15843462
TI  - Ligand-induced dimerization of Drosophila peptidoglycan recognition proteins in
      vitro.
AB  - Drosophila knockout mutants have placed peptidoglycan recognition proteins
      (PGRPs) in the two major pathways controlling immune gene expression. We now
      examine PGRP affinities for peptidoglycan. PGRP-SA and PGRP-LCx are bona fide
      pattern recognition receptors, and PGRP-SA, the peptidoglycan receptor of the
      Toll/Dif pathway, has selective affinity for different peptidoglycans. PGRP-LCx,
      the default peptidoglycan receptor of the Imd/Relish pathway, has strong affinity
      for all polymeric peptidoglycans tested and for monomeric peptidoglycan. PGRP-LCa
      does not have affinity for polymeric or monomeric peptidoglycan. Instead, PGRP
      LCa can form heterodimers with LCx when the latter is bound to monomeric
      peptidoglycan. Hence, PGRP-LCa can be said to function as an adaptor, thus adding
      a new function to a member of the PGRP family.

PMID- 15843463
TI  - Early events in the folding of four-helix-bundle heme proteins.
AB  - Topologically homologous four-helix-bundle heme proteins exhibit striking
      diversity in their refolding kinetics. Cytochrome b562 has been reported to fold
      on a sub-millisecond time scale, whereas cytochrome c' refolding requires 10 s or
      more to complete. Heme dissociation in cytochrome b562 interferes with studies of
      folding kinetics, so a variant of cytochrome b562 (cytochrome c-b562) with a
      covalent c-type linkage to the heme has been expressed in Escherichia coli. Early
      events in the electron transfer-triggered folding of Fe(II)-cytochrome c-b562,
      along with those of Fe(II)-cytochrome c556, have been examined by using time
      resolved absorption spectroscopy. Coordination of S(Met) to Fe(II) occurs within
      10 mus after reduction of the denatured Fe(III)-cytochromes, and shortly
      thereafter (100 micros) the heme spectra are indistinguishable from those of the
      folded proteins. Under denaturing conditions, carbon monoxide binds to the Fe(II)
      hemes in approximately 15 ms. By contrast, CO binding cannot compete with
      refolding in the Fe(II)-cytochromes, thereby confirming that the polypeptide
      encapsulates the heme in <10 ms. We suggest that Fe-S(Met) ligation facilitates
      refolding in these four-helix-bundle heme proteins by reducing the conformational
      freedom of the polypeptide chain.

PMID- 15843464
TI  - In vivo fragmentation of heparan sulfate by heparanase overexpression renders
      mice resistant to amyloid protein A amyloidosis.
AB  - Amyloid diseases encompass >20 medical disorders that include amyloid protein A
      (AA) amyloidosis, Alzheimer's disease, and type 2 diabetes. A common feature of
      these conditions is the selective organ deposition of disease-specific fibrillar
      proteins, along with the sulfated glycosaminoglycan, heparan sulfate. We have
      generated transgenic mice that overexpress human heparanase and have tested their
      susceptibility to amyloid induction. Drastic shortening of heparan sulfate chains
      was observed in heparanase-overproducing organs, such as liver and kidney. These
      sites selectively escaped amyloid deposition on experimental induction of
      inflammation-associated AA amyloidosis, as verified by lack of material staining
      with Congo Red, as well as lack of associated polysaccharide, whereas the same
      tissues from control animals were heavily infiltrated with amyloid. By contrast,
      the spleens of transgenic mice that failed to significantly overexpress
      heparanase contained heparan sulfate chains similar in size to those of control
      spleen and remained susceptible to amyloid deposition. Our findings provide
      direct in vivo evidence that heparan sulfate is essential for the development of
      amyloid disease.

PMID- 15843466
TI  - Essential hypertension, progressive renal disease, and uric acid: a pathogenetic
      link?
AB  - Hypertension and hypertension-associated ESRD are epidemic in society. The
      mechanisms responsible for renal progression in mild to moderate hypertension and
      those groups most at risk need to be identified. Historic, epidemiologic,
      clinical, and experimental studies on the pathogenesis of hypertension and
      hypertension-associated renal disease are reviewed and an overview/hypothesis for
      the mechanisms involved in renal progression is presented. There is increasing
      evidence that hypertension may exist in one of two forms/stages. The first stage,
      most commonly observed in early or borderline hypertension, is characterized by
      salt-resistance, normal or only slightly decreased GFR, relatively normal or mild
      renal arteriolosclerosis, and normal renal autoregulation. This group is at
      minimal risk for renal progression. The second stage, characterized by salt
      sensitivity, renal arteriolar disease, and blunted renal autoregulation, defines
      a group at highest risk for the development of microalbuminuria, albuminuria, and
      progressive renal disease. This second stage is more likely to be observed in
      blacks, in subjects with gout or hyperuricemia, with low level lead intoxication,
      or with severe obesity/metabolic syndrome. The two major mechanistic pathways for
      causing impaired autoregulation at mild to moderate elevations in BP appear to be
      hyperuricemia and/or low nephron number. Understanding the pathogenetic pathways
      mediating renal progression in hypertensive subjects should help identify those
      subjects at highest risk and may provide insights into new therapeutic maneuvers
      to slow or prevent progression.

PMID- 15843467
TI  - F1FO-ATPase activity and ATP dependence of mitochondrial energization in proximal
      tubules after hypoxia/reoxygenation.
AB  - Isolated kidney proximal tubules subjected to hypoxia/reoxygenation (H/R) have
      incomplete recovery of mitochondrial membrane potential (DeltaPsi(m)) that can be
      improved, but not normalized, by ATP in permeabilized cells as measured by
      safranin O uptake. In these studies, the mechanisms for the decreased DeltaPsi(m)
      in the tubules after H/R are further investigated and impairment of the function
      of the mitochondrial F(1)F(O)-ATPase is assessed. Normoxic control tubules had a
      small ATP-dependent component to DeltaPsi(m), but it required low micromolar
      levels of ATP, not the millimolar levels needed to support DeltaPsi(m) in tubules
      de-energized with rotenone or after H/R. Micromolar levels of ATP did not improve
      DeltaPsi(m) after either mild or severe H/R injury. The dependence of DeltaPsi(m)
      on millimolar levels of ATP after H/R decreased over time during reoxygenation.
      ATP hydrolysis by the oligomycin-sensitive, mitochondrial F(1)F(O)-ATPase was
      well preserved after H/R as long as Mg(2+) was available, indicating that
      function of both the F(1)F(O)-ATPase and of the adenine nucleotide translocase,
      which delivers nucleotides to it, are largely intact. However, ATP hydrolysis by
      the ATPase did not restore DeltaPsi(m) as much as expected from the rate of ATP
      utilization. These findings, taken together with the observation that substrate
      supported generation of DeltaPsi(m) is impaired despite intact electron
      transport, make it likely that uncoupling plays a major role in the mitochondrial
      dysfunction in proximal tubules during H/R.

PMID- 15843469
TI  - Dual effects of hypertonicity on aquaporin-2 expression in cultured renal
      collecting duct principal cells.
AB  - The driving force for renal water reabsorption is provided by the osmolarity
      gradient between the interstitium and the tubular lumen, which is subject to
      rapid physiologic variations as a consequence of water intake fluctuations. The
      effect of increased extracellular tonicity/osmolarity on vasopressin-inducible
      aquaporin-2 (AQP2) expression in immortalized mouse collecting duct principal
      cells (mpkCCD(cl4)) is investigated in this report. Increasing the osmolarity of
      the medium either by the addition of NaCl, sucrose, or urea first decreased AQP2
      expression after 3 h. AQP2 expression then increased in cells exposed to NaCl- or
      sucrose-supplemented hypertonic medium after longer periods of time (24 h), while
      urea-supplemented hyperosmotic medium had no effect. Altered AQP2 expression
      induced by both short-term (3 h) and long-term (24 h) exposure of cells to
      hypertonicity arose from changes in AQP2 gene transcription because hypertonicity
      did not modify AQP2 mRNA stability nor AQP2 protein turnover. On the long-term,
      vasopressin (AVP) and hypertonicity increased AQP2 expression in a synergistic
      manner. Hypertonicity altered neither the dose-responsiveness of AVP-induced AQP2
      expression nor cAMP-protein kinase (PKA) activity, while PKA inhibition did not
      reduce the extent of the hypertonicity-induced increase of AQP2 expression. These
      results indicate that in collecting duct principal cells: (1) a short-term
      increase of extracellular osmolarity decreases AQP2 expression through inhibition
      of AQP2 gene transcription; (2) a long-term increase of extracellular tonicity,
      but not osmolarity, enhances AQP2 expression via stimulation of AQP2 gene
      transcription; and (3) long-term hypertonicity and PKA increases AQP2 expression
      through synergistic but independent mechanisms.

PMID- 15843468
TI  - Role of matrix extracellular phosphoglycoprotein in the pathogenesis of X-linked
      hypophosphatemia.
AB  - X-linked hypophosphatemia (XLH), a disorder characterized by hypophosphatemia,
      impaired skeletal mineralization, and aberrant regulation of 1, 25(OH)(2)D(3), is
      caused by inactivating mutations of Phex, which results in the accumulation of
      putative phosphaturic factors, called phosphatonins. Matrix extracellular
      phosphoglycoprotein (Mepe) is a proposed candidate for phosphatonin. The authors
      found that Hyp mice had increased expression of the MEPE and another phosphaturic
      factor, Fgf23. To establish MEPE's role in the pathogenesis of the XLH, Mepe
      deficient mice were back-crossed onto the Hyp mouse homologue of XLH and
      phenotypes of wild-type, Mepe(-/-), Hyp, and Mepe(-/-)/Hyp mice were examined.
      Transfer of Mepe deficiency onto the Phex-deficient Hyp mouse background failed
      to correct hypophosphatemia and aberrant serum 1,25(OH)(2)D(3) levels. Increased
      Fgf23 levels in Hyp mice were not affected by superimposed Mepe deficiency. In
      addition, Mepe-deficient Hyp mice retained bone mineralization defects in vivo,
      characterized by decreased bone mineral density, reduced mineralized trabecular
      bone volume, lower flexural strength, and histologic evidence of osteomalacia;
      however, cultures of Hyp-derived bone marrow stromal cells in the absence of Mepe
      showed improved mineralization and normalization of osteoblast gene expression
      profiles observed in cells derived from Mepe-null mice. These results demonstrate
      that MEPE elevation in Hyp mice does not contribute to the hypophosphatemia
      associated with inactivating Phex mutations and is therefore not phosphatonin.

PMID- 15843470
TI  - NF-kappaB mediated IL-6 production by renal epithelial cells is regulated by c
      jun NH2-terminal kinase.
AB  - Tubular epithelial cells (TEC) play an important role in tubulointerstitial
      inflammation, a hallmark of most renal diseases, via production of cytokines and
      chemokines. In this study, the role of mitogen-activated protein kinases (MAPK)
      in regulation of the proinflammatory cytokine IL-6 in cultured human TEC in
      response to the leukocyte-derived factors IL-1, TNF-alpha, IL-17, and CD40L was
      investigated. IL-6 production induced by IL-1, TNF-alpha, and IL-17 was
      specifically inhibited by the c-jun NH(2)-terminal kinase (JNK) inhibitor
      SP600125, but not by a selective inhibitor of p38 MAPK, and was moderately
      increased when the ERK1/2 pathway was inhibited. Also for CD40L stimulation,
      inhibition of JNK resulted in a pronounced inhibition of IL-6 production.
      Although stimulation of TEC induced activation of activator protein-1 (AP-1), the
      down-stream target of JNK, reporter assays demonstrated that mutation of the AP-1
      binding site in the IL-6 promoter did not affect gene transcription. Furthermore,
      IL-1-induced transcriptional activation of the IL-6 promotor was repressed by
      SP600125 or by co-transfection of a dominant-negative expression plasmid of c-jun
      even in the absence of a functional AP-1 binding site. This suggests that IL-6
      production by renal epithelial cells is regulated by JNK, via a mechanism,
      however, independent of the AP-1 binding site. The data rather suggest that the
      JNK pathway may interfere with other signaling pathways, involving NF-kappaB and
      possibly ERK.

PMID- 15843471
TI  - Cultured podocytes establish a size-selective barrier regulated by specific
      signaling pathways and demonstrate synchronized barrier assembly in a calcium
      switch model of junction formation.
AB  - Podocytes form unique cell-cell junctions (slit diaphragms) that are central to
      glomerular selectivity, although regulation and mechanisms of slit diaphragm
      assembly are poorly understood. With the use of cultured podocytes, a
      paracellular permeability flux assay was established to characterize properties
      of the size-selective barrier. Paracellular flux of differentiated podocytes was
      measured using anionic fluorescent dextrans of 3, 10, 40, and 70 kD. Podocytes
      form a highly selective barrier with a 160-fold difference in flux from the 3-kD
      dextran (11 pmol/min) to the 70-kD dextran (0.06 pmol/min). Barrier development
      was dependent on podocyte differentiation and not affected by dextran charge.
      Puromycin, a known podocyte toxin, increased flux 250% in a dose-dependent manner
      without affecting cell viability. Screening with modulators of specific signaling
      pathways identified reversible increases in flux with Src tyrosine and Rho kinase
      inhibition. The calcium switch model of epithelial junction assembly was modified
      to determine whether podocytes regulate barrier assembly. When cultured in low
      calcium for 90 min, flux increased by 300% and consistently returned to baseline
      24 to 48 h after switching to normal calcium. Similar to classical epithelial
      junctions, barrier recovery occurred in the presence of cyclohexamide, an
      inhibitor of protein synthesis. During the calcium switch, there were reversible
      changes in localization and detergent solubility of the slit diaphragm protein ZO
      1 and alpha-actinin-4, whereas nephrin and podocin solubility were unchanged.
      Taken together, these findings demonstrate that cultured podocytes develop a
      selective size barrier that is regulated by specific signaling pathways, and
      similar to classical epithelial junctions, podocytes demonstrate synchronized
      assembly of the barrier.

PMID- 15843472
TI  - Statins prevent oxidized LDL-induced injury of glomerular podocytes by activating
      the phosphatidylinositol 3-kinase/AKT-signaling pathway.
AB  - The injury of podocytes is associated with alterations of the glomerular size
      selective barrier to proteins. In this study, oxidized LDL (oxLDL) but not native
      LDL induced apoptosis in human cultured podocytes and reduced Akt activity and P
      Akt/Akt ratio. Moreover, oxLDL-induced redistribution and loss of nephrin, an
      adhesion molecule specific for the glomerular slit diaphragm. Nephrin reduction
      was preceded by inhibition of nephrin tyrosine phosphorylation and of its
      association with p85 phosphatidylinositol 3-kinase (PI3K). Moreover, three
      different statins, mevastatin, pravastatin, and simvastatin, inhibited in a dose
      dependent manner apoptosis and loss of nephrin induced by oxLDL by stimulating
      Akt activity. In addition, simvastatin significantly increased the expression of
      nephrin protein and mRNA by podocytes. The protective effects of statins were
      blocked by treatment of podocytes with two unrelated pharmacologic inhibitors of
      PI3K, LY294002 and wortmannin, suggesting a role for PI3K, and by mevalonate,
      indicating dependency on HMG-CoA reductase activity. Statins directly stimulated
      Akt phosphorylation ad activity. Finally, oxLDL induced a retraction of cultured
      podocytes and an increase in the albumin diffusion across their monolayer that
      was inhibited by treatment with statins. In conclusion, statins reduced the oxLDL
      induced apoptosis and loss of nephrin in glomerular podocytes. The statin-induced
      Akt activation may protect from the loss of nephrin by an inhibition of its
      redistribution and shedding and by a stimulation of its synthesis. These data
      provide a rationale for the anti-proteinuric effect of statins.

PMID- 15843473
TI  - Protein kinase Cbeta inhibition attenuates osteopontin expression, macrophage
      recruitment, and tubulointerstitial injury in advanced experimental diabetic
      nephropathy.
AB  - Tubulointerstitial macrophage accumulation is an important marker of prognosis
      that correlates closely with declining renal function in a range of human and
      experimental diseases, including diabetic nephropathy. These inflammatory cells
      are rich in the profibrotic growth factor TGF-beta such that their presence in
      areas of injury is frequently associated with tissue fibrosis. The migration of
      macrophages occurs in response to the site-specific production of chemokines,
      with osteopontin closely associated with their trafficking into the
      tubulointerstitium of the kidney. Although cell culture studies indicate that
      protein kinase C (PKC) mediates the expression of osteopontin, its role in the in
      vivo setting is unknown. Accordingly, Ren-2 control and diabetic rats that were
      treated with or without the specific PKC-beta isoform inhibitor ruboxistaurin (10
      mg/kg per d) were examined. After 12 wk, diabetic rats showed increases in
      osteopontin expression in tubular epithelial cells of the cortex in association
      with macrophage infiltration, interstitial fibrosis, and activity of TGF-beta as
      indicated by the expression of its receptor activated protein phospho-Smad2 (P <
      0.05 for all parameters). Ruboxistaurin treatment significantly attenuated these
      parameters (P < 0.05) in diabetic rats without affecting either BP or glycemic
      control. These findings suggest that osteopontin and macrophage accumulation may
      play a role in the tubulointerstitial injury in diabetic nephropathy and that
      inhibition of osteopontin expression may be one of the mechanisms by which
      inhibition of the beta-isoform of PKC confers a renoprotective effect.

PMID- 15843474
TI  - Cited1 is a bifunctional transcriptional cofactor that regulates early nephronic
      patterning.
AB  - In a screen to identify factors that regulate the conversion of mesenchyme to
      epithelium during the early stages of nephrogenesis, it was found that the Smad4
      interacting transcriptional cofactor, Cited1, is expressed in the condensed cap
      mesenchyme surrounding the tip of the ureteric bud (UB), is downregulated after
      differentiation into epithelia, and has the capacity to block UB branching and
      epithelial morphogenesis in cultured metanephroi. Cited1 represses Wnt/beta
      catenin but activates Smad4-dependent transcription involved in TGF-beta and Bmp
      signaling. By modifying these pathways, Cited1 may coordinate cellular
      differentiation and survival signals that regulate nephronic patterning in the
      metanephros.

PMID- 15843475
TI  - NEPH2 is located at the glomerular slit diaphragm, interacts with nephrin and is
      cleaved from podocytes by metalloproteinases.
AB  - The NEPH family comprises three transmembrane proteins of the Ig superfamily
      interacting with the glomerular slit diaphragm proteins podocin and ZO-1. NEPH1
      binds to nephrin, another component of the slit diaphragm, and loss of either
      partner causes heavy proteinuria. NEPH2, which is strongly conserved among a
      large number of species, is also expressed in the kidney; however, its function
      is unknown. The authors raised NEPH2 antisera to demonstrate NEPH2 expression in
      a variety of mouse tissues, including the kidney and a podocyte cell line. The
      authors localized the expression of NEPH2 to the glomerular slit diaphragm by
      electron microscopy and show NEPH2 homodimerization and specific interactions
      with the extracellular domain of nephrin in vitro and in vivo. NEPH1, however,
      failed to interact with NEPH2. The authors detected immunoreactive NEPH2 in urine
      of healthy subjects, suggesting that the extracellular domain is cleaved under
      physiologic conditions. These findings were confirmed in vitro in podocyte cell
      culture. Shedding is increased by tyrosine phosphatase inhibitors and diminished
      by GM6001, an inhibitor of metalloproteinases. Overexpression experiments
      indicate an involvement of the MT1-matrix metalloproteinase. The results suggest
      a role for NEPH2 in the organization and/or maintenance of the glomerular slit
      diaphragm that may differ from the functions of NEPH1 and nephrin.

PMID- 15843476
TI  - Quantal encoding of information in a retinal ganglion cell.
AB  - A retinal ganglion cell receives information about a white-noise stimulus as a
      flickering pattern of glutamate quanta. The ganglion cell reencodes this
      information as brief bursts of one to six spikes separated by quiescent periods.
      When the stimulus is repeated, the number of spikes in a burst is highly
      reproducible (variance < mean) and spike timing is precise to within 10 ms,
      leading to an estimate that each spike encodes about 2 bits. To understand how
      the ganglion cell reencodes information, we studied the quantal patterns by
      repeating a white-noise stimulus and recording excitatory currents from a voltage
      clamped, brisk-sustained ganglion cell. Quanta occurred in synchronous bursts of
      3 to 65; the resulting postsynaptic currents summed to form excitatory
      postsynaptic currents (EPSCs). The number of quanta in an EPSC was only
      moderately reproducible (variance = mean), quantal timing was precise to within
      14 ms, and each quantum encoded 0.1-0.4 bit. In conclusion, compared to a spike,
      a quantum has similar temporal precision, but is less reproducible and encodes
      less information. Summing multiple quanta into discrete EPSCs improves the
      reproducibility of the overall quantal pattern and contributes to the
      reproducibility of the spike train.

PMID- 15843477
TI  - Microsecond precision of phase delay in the auditory system of the barn owl.
AB  - The auditory system encodes time with sub-millisecond accuracy. To shed new light
      on the basic mechanism underlying this precise temporal neuronal coding, we
      analyzed the neurophonic potential, a characteristic multiunit response, in the
      barn owl's nucleus laminaris. We report here that the relative time measure of
      phase delay is robust against changes in sound level, with a precision sharper
      than 20 micros. Absolute measures of delay, such as group delay or signal-front
      delay, had much greater temporal jitter, for example due to their strong
      dependence on sound level. Our findings support the hypothesis that phase delay
      underlies the sub-millisecond precision of the representation of interaural time
      difference needed for sound localization.

PMID- 15843478
TI  - Effect of saccadic adaptation on localization of visual targets.
AB  - Objects flashed briefly around the time of a saccadic eye movement are grossly
      mislocalized by human subjects, so they appear to be compressed toward the
      endpoint of the saccade. In this study, we investigate spatial localization
      during saccadic adaptation to examine whether the focus of compression tends
      toward the intended saccadic target or at the endpoint of the actual (adapted)
      movement. We report two major results. First, that peri-saccadic focus of the
      compression did not occur at the site of the initial saccadic target, but tended
      toward the actual landing site of the saccade. Second, and more surprisingly, we
      observed a large long-term perceptual distortion of space, lasting for hundreds
      of milliseconds. This distortion did not occur over the whole visual field but
      was limited to a local region of visual space around the saccade target,
      suggesting that saccadic adaptation induces a visuo-topic remapping of space. The
      results imply that the mechanisms controlling saccadic adaptation also affect
      perception of space and point to a strong perceptual plasticity coordinated with
      the well-documented plasticity of the motor system.

PMID- 15843479
TI  - Long-latency afferent inhibition during selective finger movement.
AB  - Stimulation of a peripheral nerve of a hand at rest modulates excitability in the
      motor cortex and, in particular, leads to inhibition when applied at an interval
      of approximately 200 ms (long-latency afferent inhibition; LAI). Surround
      inhibition (SI) is the process that inhibits neighboring muscles not involved in
      a particular task. The neuronal mechanisms of SI are not known, and it is
      possible that LAI might contribute to it. Using transcranial magnetic stimulation
      (TMS) with and without movement of the index finger, the motor-evoked potentials
      (MEPs) were measured of two functionally distinct target muscles of the hand
      (abductor digiti minimi muscle = ADM, 1st dorsal interosseus muscle = FDI).
      Electrical stimulation was applied 180 ms before TMS to either the fifth finger
      or the index finger. Both homotopic and heterotopic finger stimulation resulted
      in LAI without movement. With index finger movement, motor output further
      decreased with homo- and heterotopic stimulation in the ADM. In the moving FDI,
      however, there was no change with either homo- or heterotopic stimulation.
      Additionally, in the unstimulated movement trials, LAI increased with the amount
      of unintentional co-activation that occurred despite attempts to maintain the ADM
      at rest. However, with finger stimulation added, there were almost no increased
      MEPs despite co-activation. These findings suggest that LAI increases during
      movement and can enhance SI.

PMID- 15843480
TI  - Growth factors mobilize multiple pools of KCa channels in developing
      parasympathetic neurons: role of ADP-ribosylation factors and related proteins.
AB  - In developing ciliary ganglion (CG) neurons, movement of functional large
      conductance (BK type) Ca(2+)-activated K+ (K(Ca)) channels to the cell surface is
      stimulated by the endogenous growth factors TGF(beta)1 and beta-neuregulin-1
      (NRG1). Here we show that a brief NRG1 treatment (0.5-1.5 h) mobilizes K(Ca)
      channels in a post-Golgi compartment, but longer treatments (>3.5 h) mobilize
      K(Ca) channels located in the endoplasmic reticulum or Golgi apparatus.
      Specifically, the effects of 3.5 h NRG1 treatment were completely blocked by
      treatments that disrupt Golgi apparatus function. These include inhibition of
      microtubules, or inhibition of the ADP-ribosylation factor-1 (ARF1) system by
      brefeldin A, by over-expression of dominant-negative ARF1, or over-expression of
      an ARF1 GTPase-activating protein that blocks ARF1 cycling between GTP- and GDP
      bound states. These treatments had no effect on stimulation of K(Ca) evoked by
      1.5 h treatment with NRG1, indicating that short-term responses to NRG1 do not
      require an intact Golgi apparatus. By contrast, both the acute and sustained
      effects of NRG1 were inhibited by treatments that block trafficking processes
      that occur close to the plasma membrane. Thus mobilization of K(Ca) was blocked
      by treatments than inhibit ADP-ribosylation factor-6 (ARF6) signaling, including
      overexpression of dominant-negative ARF6, dominant-negative ARNO, or dominant
      negative phospholipase D1. TGF(beta)1, the effects of which on K(Ca) are much
      slower in onset, is unable to selectively mobilize channels in the post-Golgi
      pool, and its effects on K(Ca) are completely blocked by inhibition of
      microtubules, Golgi function and also by plasma membrane ARF6 and phospholipase
      D1 signaling.

PMID- 15843481
TI  - Involvement of kv1 potassium channels in spreading acidification and depression
      in the cerebellar cortex.
AB  - Spreading acidification and depression (SAD) is a form of propagated activity in
      the cerebellar cortex characterized by acidification and a transient depression
      in excitability. This study investigated the role of Kv1 potassium channels in
      SAD using neutral red, flavoprotein autofluorescence, and voltage-sensitive dye
      optical imaging in the mouse cerebellar cortex, in vivo. The probability of
      evoking SAD was greatly increased by blocking Kv1.1 as well as Kv1.2 potassium
      channels by their specific blockers dendrotoxin K (DTX-K) and tityustoxin (TsTX),
      respectively. DTX-K not only greatly lowered the threshold for evoking SAD but
      also resulted in multiple cycles of spread and spontaneous SAD. The occurrence of
      spontaneous SAD originating from spontaneous parallel fiber-like beams of
      activity suggests that blocking Kv1 channels increased parallel fiber
      excitability. This was confirmed by the generation of parallel fiber-like beams
      with the microinjection of glutamate into the upper molecular layer in the
      presence of DTX-K. The dramatic effects of DTX-K suggest a possible connection
      between SAD and episodic ataxia type 1 (EA1), a Kv1.1 potassium channelopathy.
      The threshold for evoking SAD was significantly lowered in the Kv1.1 heterozygous
      knockout mouse compared with wild-type littermates. Carbamazepine and
      acetazolamide, both effective in the treatment of EA1, significantly decreased
      the likelihood of evoking SAD. Blocking GABAergic neurotransmission did not alter
      the effectiveness of DTX-K. The cyclin D2 null mouse, which lacks cerebellar
      stellate cells, also exhibited SAD. Therefore blocking Kv1 potassium channels
      establishes the conditions needed to generate SAD. Furthermore, the results are
      consistent with the hypothesis that SAD may underlie the transient attacks of
      ataxia characterizing EA1.

PMID- 15843482
TI  - Delay-period activity in visual, visuomovement, and movement neurons in the
      frontal eye field.
AB  - In the present study, we examined the role of frontal eye field neurons in the
      maintenance of spatial information in a delayed-saccade paradigm. We found that
      visual, visuomovement, and movement neurons conveyed roughly equal amounts of
      spatial information during the delay period. Although there was significant delay
      period activity in individual movement neurons, there was no significant delay
      period activity in the averaged population of movement neurons. These
      contradictory results were reconciled by the finding that the population of
      movement neurons with memory activity consisted of two subclasses of neurons, the
      combination of which resulted in the cancellation of delay-period activity in the
      population of movement neurons. One subclass consisted of neurons with
      significantly greater delay activity in the preferred than in the null direction
      ("canonical"), whereas the other subclass consisted of neurons with significantly
      greater delay activity in the null direction than in the preferred direction
      ("paradoxical"). Preferred direction was defined by the saccade direction that
      evoked the greatest movement-related activity. Interestingly, the peak saccade
      related activity of canonical neurons occurred before the onset of the saccade,
      whereas the peak saccade-related activity of paradoxical neurons occurred after
      the onset of the saccade. This suggests that the former, but not the latter, are
      directly involved in triggering saccades. We speculate that paradoxical neurons
      provide a mechanism by which spatial information can be maintained in a saccade
      generating circuit without prematurely triggering a saccade.

PMID- 15843483
TI  - Cross-orientation suppression: monoptic and dichoptic mechanisms are different.
AB  - The response of a cell in the primary visual cortex to an optimally oriented
      grating is suppressed by a superimposed orthogonal grating. This cross
      orientation suppression (COS) is exhibited when the orthogonal and optimal
      stimuli are presented to the same eye (monoptically) or to different eyes
      (dichoptically). A recent study suggested that monoptic COS arises from
      subcortical processes; however, the mechanisms underlying dichoptic COS were not
      addressed. We have compared the temporal frequency tuning and stimulus adaptation
      properties of monoptic and dichoptic COS. We found that dichoptic COS is best
      elicited with lower temporal frequencies and is substantially reduced after
      prolonged adaptation to a mask grating. In contrast, monoptic COS is more
      pronounced with mask gratings at much higher temporal frequencies and is less
      prone to stimulus adaptation. These results suggest that monoptic COS is mediated
      by subcortical mechanisms, whereas intracortical inhibition is the mechanism for
      dichoptic COS.

PMID- 15843484
TI  - Supplementary motor area encodes reward expectancy in eye-movement tasks.
AB  - Neural activity signifying the expectation of reward has been found recently in
      many parts of the brain, including midbrain and cortical structures. These
      signals can facilitate goal-directed behavior or the learning of new skills based
      on reinforcements. Here we show that neurons in the supplementary motor area
      (SMA), an area concerned with movements of the body and limbs, also carry a
      reward expectancy signal in the postsaccadic period of oculomotor tasks. While
      the monkeys performed blocks of memory-guided and object-based saccades, the
      neurons discharged a burst after a approximately 200-ms delay following the
      target-acquiring saccade in the memory task but often fired concurrently with the
      target-acquiring saccade in the object task. The hypothesis that this
      postsaccadic bursting activity reflects the expectation of a reward was tested
      with a series of manipulations to the memory-guided saccade task. It was found
      that although the timing of the bursting activity corresponds to a visual
      feedback stimulus, the visual feedback is not required for the neurons to
      discharge a burst. Second, blocks of no-reward trials reveal an extinction of the
      bursting activity as the monkeys come to understand that they would not be
      rewarded for properly generated saccades. Finally, the delivery of unexpected
      rewards confirmed that in many of the neurons, the activity is not related to a
      motor plan to acquire the reward (e.g., licking). Thus we conclude that reward
      expectancy is represented by the activity of SMA neurons, even in the context of
      an oculomotor task. These results suggest that the reward expectancy signal is
      broadcast over a large extent of motor cortex, and may facilitate the learning of
      new, coordinated behavior between different body parts.

PMID- 15843485
TI  - Eye-centered, head-centered, and complex coding of visual and auditory targets in
      the intraparietal sulcus.
AB  - The integration of visual and auditory events is thought to require a joint
      representation of visual and auditory space in a common reference frame. We
      investigated the coding of visual and auditory space in the lateral and medial
      intraparietal areas (LIP, MIP) as a candidate for such a representation. We
      recorded the activity of 275 neurons in LIP and MIP of two monkeys while they
      performed saccades to a row of visual and auditory targets from three different
      eye positions. We found 45% of these neurons to be modulated by the locations of
      visual targets, 19% by auditory targets, and 9% by both visual and auditory
      targets. The reference frame for both visual and auditory receptive fields ranged
      along a continuum between eye- and head-centered reference frames with
      approximately 10% of auditory and 33% of visual neurons having receptive fields
      that were more consistent with an eye- than a head-centered frame of reference
      and 23 and 18% having receptive fields that were more consistent with a head-
      than an eye-centered frame of reference, leaving a large fraction of both visual
      and auditory response patterns inconsistent with both head- and eye-centered
      reference frames. The results were similar to the reference frame we have
      previously found for auditory stimuli in the inferior colliculus and core
      auditory cortex. The correspondence between the visual and auditory receptive
      fields of individual neurons was weak. Nevertheless, the visual and auditory
      responses were sufficiently well correlated that a simple one-layer network
      constructed to calculate target location from the activity of the neurons in our
      sample performed successfully for auditory targets even though the weights were
      fit based only on the visual responses. We interpret these results as suggesting
      that although the representations of space in areas LIP and MIP are not easily
      described within the conventional conceptual framework of reference frames, they
      nevertheless process visual and auditory spatial information in a similar
      fashion.

PMID- 15843486
TI  - Three-dimensional quantitative structure-activity relationship analysis of
      cytochromes p450: effect of incorporating higher-affinity ligands and potential
      new applications.
AB  - Recently, two new classes of reversible inhibitors, the benzbromarones (BZBRs)
      and the N-3 substituted phenobarbitals (PBs), were used to study the active site
      characteristics of CYP2C9 and 2C19, respectively. Since these ligands are some of
      the first CYP2C ligands to extend into the low nanomolar K(i) range (K(i) < 100
      nM), they were subjected to three-dimensional quantitative structure-activity
      relationship (3D-QSAR) analysis. Given that BZBRs or the PB ligands bind very
      tightly, it can be assumed that these structures complement the binding pocket(s)
      for these enzymes. Thus, the resulting models should output a 3D arrangement of
      interaction sites predicted to be important for near optimal binding to the
      CYP2C9 and CYP2C19 enzymes. These predicted interaction regions may then improve
      the ability to predict drug-drug interactions. The resulting models generated
      from these new high affinity ligands are discussed, as are novel uses of 3D-QSAR
      and molecular modeling techniques that may be useful in the study of cytochromes
      P450 specifically.

PMID- 15843487
TI  - Monoclonal nicotine-specific antibodies reduce nicotine distribution to brain in
      rats: dose- and affinity-response relationships.
AB  - Vaccination against nicotine is being studied as a potential treatment for
      nicotine dependence. Some of the limitations of vaccination, such as variability
      in antibody titer and affinity, might be overcome by instead using passive
      immunization with nicotine-specific monoclonal antibodies. The effects of
      antibodies on nicotine distribution to brain were studied using nicotine-specific
      monoclonal antibodies (NICmAbs) with K(d) values ranging from 60 to 250 nM and a
      high-affinity polyclonal rabbit antiserum (K(d) = 1.6 nM). Pretreatment with
      NICmAbs substantially increased the binding of nicotine in serum after a single
      nicotine dose, reduced the unbound nicotine concentration in serum, and reduced
      the distribution of nicotine to brain. Efficacy was directly related to antibody
      affinity for nicotine. Efficacy of the highest affinity NICmAb, NICmAb311, was
      dose-related, with the highest dose reducing nicotine distribution to brain by
      78%. NICmAb311 decreased nicotine clearance by 90% and prolonged the terminal
      half-life of nicotine by 120%. At equivalent doses, NICmAb311 was less effective
      than the higher affinity rabbit antiserum but comparable efficacy could be
      achieved by increasing the NICmAb311 dose. These data suggest that passive
      immunization with nicotine-specific monoclonal antibodies substantially alters
      nicotine pharmacokinetics in a manner similar to that previously reported for
      vaccination against nicotine. Antibody efficacy is a function of both dose and
      affinity for nicotine.

PMID- 15843488
TI  - Tissue distribution and ontogeny of mouse organic anion transporting polypeptides
      (Oatps).
AB  - Organic anion-transporting polypeptides (Oatps) are Na(+)-independent solute
      carriers for cellular uptake of organic compounds. The purpose of this study is
      to determine 1) the constitutive mRNA expression of the 15 mouse Oatp genes in 12
      tissues, 2) whether there are gender differences in Oatp expression, and 3) the
      ontogenic expression of Oatps in liver and kidney. The mRNA expression of the 15
      mouse Oatps was quantified using the branched DNA technique. Oatp1a1, 1a4, 1b2,
      and 2b1 are expressed in liver at relatively high levels, with Oatp1b2 being
      exclusively expressed in liver. Oatp1a1, 1a6, 3a1, and 4c1 are highly expressed
      in kidney. Oatp1a4 and 1c1 are highly expressed in brain. Oatp1a5, 6b1, 6c1, and
      6d1 are predominant in testes. Oatp2a1, 4a1, and 5a1 are predominantly expressed
      in placenta. In liver, expression of Oatp1a1 was male-predominant, whereas
      expression of Oatp1a4 and 1a6 was female-predominant. In kidney, expression of
      Oatp1a1, 3a1, and 4c1 was higher in males than in females. Hepatic expression of
      Oatp1a1, 1a4, 1a6, 1b2, and 2b1 gradually increased after birth and reached adult
      levels by 6 weeks of age. Only Oatp2a1 was expressed at adult levels at birth. In
      kidney, expression of mouse Oatp1a1, 1a6, and 3a1 was lower at birth than at 6
      weeks of age, whereas expression of mouse Oatp1a4, 2a1, and 2b1 was similar at
      birth and at 6 weeks of age. These data on the tissue distribution and ontogenic
      expression of mouse Oatps will aid in understanding the pharmacokinetics and
      toxicokinetics of drugs and other chemicals.

PMID- 15843489
TI  - Prevention of Mrp2 activity impairment in ethinylestradiol-induced cholestasis by
      ursodeoxycholate in the rat.
AB  - Ethinylestradiol (EE) induces cholestasis by affecting bile salt-dependent and 
      independent fractions of the bile flow. The decrease in bile salt-independent
      flow is thought to be due, in part, to a reduction in the expression of the
      canalicular transporter Mrp2. The impact of modulation of Mrp2 function by sodium
      ursodeoxycholate (UDC) in EE cholestasis is unknown. We evaluated the protective
      effect of UDC on EE-induced impairment of Mrp2 activity in vivo and in isolated
      hepatocytes, by using the substrate dinitrophenyl S-glutathione (DNP-SG). EE was
      administered to male Wistar rats at a dose of 5 mg/kg s.c. for 5 days. UDC was
      coadministered with EE at a dose of 25 mg/kg b.wt. i.p. for the same period. EE
      alone reduced DNP-SG biliary excretion by 55% when compared with controls.
      Coadministration with UDC partially restored the alteration. Secretion rate of
      DNP-SG was decreased by 30% in isolated hepatocytes from EE-treated rats, but,
      contrary to in vivo results, UDC coadministration did not restore DNP-SG
      transport, likely as a consequence of bile salt washout resulting from the
      isolation procedure. As a confirmation, tauroursodeoxycholate hepatocyte
      preloading significantly increased Mrp2 activity. Western blotting analysis of
      Mrp2 indicated that EE administration significantly reduced its level in total
      and plasma membranes and that UDC coadministration failed to revert this
      alteration. In conclusion, UDC improvement in Mrp2 transport activity in vivo
      likely derived from a direct enhancement of Mrp2 function rather than from a
      restoration of its expression levels. This provides a novel mechanism explaining
      the beneficial effects of UDC in EE-induced cholestasis.

PMID- 15843490
TI  - Regulation of the cell surface expression of human BCRP/ABCG2 by the
      phosphorylation state of Akt in polarized cells.
AB  - Human breast cancer resistance protein (BCRP/ABCG2) is believed to act as an
      efflux pump to protect the body from drugs and toxins. BCRP is known to accept
      many kinds of endogenous and exogenous compounds as substrates and to be
      localized on the apical membrane of various tissues. Expression of BCRP is also
      reported on the side population cells, and a recent report suggested involvement
      of Akt in the modulation of the side population phenotype. In the present study,
      we have characterized the effect of Akt on the polarized expression of BCRP using
      LLC-PK1 cells. After treatment with phosphatidylinositol 3-kinase (PI3K)
      inhibitors, internalization of stably transfected BCRP from the apical surface
      was observed after immunohistochemical staining, and the relative expression
      level of BCRP on the cell surface decreased to 49 +/- 14 and 51 +/- 8% of the
      control for LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one
      hydrochloride] and wortmannin treatment, respectively. This phenomenon was
      supported by the observation of internalized BCRP in presence of dominant
      negative-Akt. When the cells were treated with epidermal growth factor, the cell
      surface expression of BCRP was increased to 228 +/- 43% of the control
      accompanied by Akt stimulation. These results suggest that the relative
      expression of BCRP on the cell surface is regulated by the PI3K-Akt signaling
      pathway with a positive correlation in polarized cells. Alteration in Akt
      activities may influence the cellular extrusion of BCRP substrates by modifying
      epithelial BCRP localization.

PMID- 15843491
TI  - Identification of cytochrome P450 and arylamine N-acetyltransferase isoforms
      involved in sulfadiazine metabolism.
AB  - Sulfadiazine hydroxylamine has been postulated to be the mediator of the greatly
      increased rates of adverse reactions to sulfadiazine experienced by people with
      human immunodeficiency virus infection. Therefore, we investigated the in vitro
      human cytochrome P450 (P450) and N-arylamine acetyltransferase (detoxification)
      metabolism of sulfadiazine. Formation of both the hydroxylamine and 4-hydroxy
      sulfadiazine was NADPH-dependent in human liver microsomes (HLM). The average
      K(m) (+/-S.D.) and V(max) in HLM (n = 3) for hydroxylamine formation was 5.7 +/-
      2.2 mM and 185 +/- 142 pmol/min/mg, respectively. Significant (p < 0.05)
      inhibition by selective P450 isoform inhibitor sulfaphenazole (2.1 microM;
      CYP2C9) indicated a role for CYP2C9 in the formation of the hydroxylamine.
      Hydroxylamine formation correlated strongly with tolbutamide 4-hydroxylation
      (CYP2C8/9) in HLM (r = 0.76, p < or = 0.004, n = 12). Fluconazole (CYP2C9/19 and
      CYP3A4 inhibitor at clinical concentrations) inhibited hydroxylamine formation,
      with one-enzyme model K(i) estimates ranging from 9 to 40 microM. Acetylation of
      sulfadiazine in human liver cytosol (HLC) correlated strongly with NAT2 activity
      as measured by sulfamethazine N-acetylation (r = 0.92, p < 0.001, n = 12). The
      average K(m) (+/-S.D.) and V(max) in HLC (n = 3) was 3.1 +/- 1.7 mM and 221.8 +/-
      132.3 pmol/min/mg, respectively. The polymorphic acetylation of sulfadiazine may
      predispose slow acetylator patients to adverse reactions to sulfadiazine. On the
      basis of our K(i) estimates, clinical fluconazole concentrations of 25 microM
      would produce decreases of 40 to 70% in hepatic-mediated hydroxylamine
      production. Therefore, we predict that fluconazole may prove useful in the clinic
      as an in vivo inhibitor of sulfadiazine hydroxylamine formation to suppress
      adverse reactions to this drug.

PMID- 15843492
TI  - Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes
      responsible in human liver microsomes.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs), used for the treatment of pain and
      inflammation, are eliminated primarily through conjugation with polar sugar
      moieties to form glucuronides. Glucuronidation is catalyzed by the UDP
      glucuronosyltransferases (UGT) superfamily. An inverse relationship may exist
      between glucuronidation activity and NSAID efficacy; however, specific UGTs
      catalyzing conjugation of the structurally diverse NSAIDs have yet to be
      identified systematically. Therefore, NSAID glucuronidation activity by 12
      individually expressed UGTs was investigated by liquid chromatography-tandem mass
      spectrometry. The relative rates of NSAID glucuronidation varied among UGT
      enzymes examined, demonstrating specificity of the individual UGTs toward
      selected NSAIDs. Kinetic parameters were determined for expressed UGT Supersomes
      and compared with parameters determined in pooled human liver microsomes (HLMs).
      Comparison of K(m) values suggested roles for UGTs 1A3 and 2B7 in indene
      glucuronidation and UGTs 1A9, 2B4, and 2B7 in profen glucuronidation. Inhibitory
      studies in pooled HLMs support the role of UGTs 1A1, 1A3, 1A9, 2B4, and 2B7 in
      the glucuronidation of ibuprofen, flurbiprofen, and ketoprofen. Bilirubin did not
      inhibit indomethacin or diclofenac glucuronidation, suggesting that UGT1A1 was
      not involved in catalysis. Imipramine did not inhibit glucuronidation of
      sulindac, sulindac sulfone, indomethacin, or naproxen in pooled HLMs, suggesting
      that UGT1A3 was not a principal hepatic catalyst. Nevertheless, multiple UGT
      enzymes, most notably UGTs 1A1, 1A9, 2B4, and 2B7, seem to be involved in the
      hepatic catalysis of NSAID glucuronidation.

PMID- 15843493
TI  - Mouse oocytes regulate metabolic cooperativity between granulosa cells and
      oocytes: amino acid transport.
AB  - A search for genes expressed more highly in mouse cumulus cells than mural
      granulosa cells by subtraction hybridization yielded Slc38a3. SLC38A3 is a sodium
      coupled neutral amino acid transporter having substrate preference for l
      glutamate, l-histidine, and l-alanine. Detectable levels of Slc38a3 mRNA were
      found by in situ hybridization in granulosa cells of large preantral follicles,
      but levels were higher in all granulosa cells of small antral follicles;
      expression became limited to cumulus cells of large antral follicles. Expression
      of Slc38a3 mRNA in granulosa cells was promoted by fully grown oocytes from
      antral follicles but not by growing oocytes from preantral follicles. Fully grown
      oocytes were dependent on cumulus cells for uptake of l-alanine and l-histidine
      but not l-leucine. Fully grown but not growing oocytes secreted one or more
      paracrine factors that promoted cumulus cell uptake of all three amino acids but
      of l-alanine and l-histidine to a much greater extent than l-leucine. Uptake of l
      leucine appeared dependent primarily on contact-mediated signals from fully grown
      oocytes. Fully grown oocytes also promoted elevated levels of Slc38a3 mRNA and l
      alanine transport by preantral granulosa cells, but growing oocytes did not.
      Therefore, fully grown oocytes secrete one or more paracrine factors that promote
      cumulus cell uptake of amino acids that oocytes themselves transport poorly.
      These amino acids are likely transferred to oocytes via gap junctions. Thus,
      oocytes use paracrine signals to promote their own development via metabolic
      cooperativity with cumulus cells. The ability of oocytes to mediate this
      cooperativity is developmentally regulated and acquired only in later stages of
      oocyte development.

PMID- 15843494
TI  - Effect of female age on mouse oocyte developmental competence following
      mitochondrial injury.
AB  - Oocytes from aging ovaries contain mitochondria with morphological and genetic
      flaws. How these flaws relate to phenotypes of oocyte developmental compromise
      associated with clinical infertility is not well understood. This study was
      conducted to investigate the role of mitochondria in the developmental
      compromises observed with female aging using a mouse model of mitochondrial
      dysfunction. Oocytes obtained from aging (30-40 wk) (C57BL/6J x CBACaH)F1
      (B6CBAF1) hybrid female mice were photosensitized with mitochondrial fluorophore
      rhodamine-123 for variable durations and compared to similarly treated oocytes
      derived from pubertal mice (4-6 wk). Blastocyst development of normally
      fertilized oocytes from both age-groups correlated negatively in mathematically
      unique profiles with irradiation time, with a more sudden decline in development
      for oocytes from aging mice. Complete inhibition of blastocyst development
      occurred following a shorter duration of photosensitization for oocytes from
      aging compared to pubertal animals (60 vs. 90 sec). Prolonged photosensitization
      resulted in mitochondrial uncoupling and promoted localized generation of
      reactive oxygen species, mitochondrial permeabilization, and apoptotic
      phenotypes. Thus, aging oocytes are more developmentally sensitive to
      mitochondrial damage than pubertal oocytes but undergo similar metabolic and
      apoptotic responses. These and future findings may encourage further optimization
      of laboratory-based strategies to minimize mitochondrial injury to oocytes,
      particularly those from older women, and improve clinical outcomes for women with
      age-related etiologies of infertility.

PMID- 15843497
TI  - The p53 inhibitor pifithrin-alpha is a potent agonist of the aryl hydrocarbon
      receptor.
AB  - The tumor suppressor protein p53 is currently a target of emerging drug therapies
      directed toward neurodegenerative diseases, such as Alzheimer's and Parkinson's,
      and side effects associated with cancer treatments. Of this group of drugs, the
      best characterized is pifithrin-alpha, a small molecule that inhibits p53
      dependent apoptosis through an undetermined mechanism. In this study, we have
      used a number of molecular approaches to test the hypothesis that pifithrin-alpha
      acts as an aryl hydrocarbon receptor (AhR) agonist and, in this manner, inhibits
      the actions of p53. Toward this end, we have found that pifithrin-alpha is a
      potent AhR agonist as determined by its ability to bind the AhR, induce formation
      of its DNA binding complex, activate reporter activity, and up-regulate the
      classic AhR target gene CYP1A1. However, examination of its ability to inhibit
      p53-mediated gene activation and apoptosis revealed that these actions occurred
      via an AhR-independent manner. The significance of this study is based on the
      fact that activation of the AhR is typically associated with an increase in phase
      I and phase II metabolizing enzymes and adverse biological events such as tumor
      promotion that may contribute to untoward effects of pifithrin-alpha. Hence, this
      work will aid in the future design of more specific members of this important
      class of p53 inhibitors for use in a clinical setting.

PMID- 15843495
TI  - Modulation of cytokine-induced cyclooxygenase 2 expression by PPARG ligands
      through NFkappaB signal disruption in human WISH and amnion cells.
AB  - Cyclooxygenase (COX) activity increases in the human amnion in the settings of
      term and idiopathic preterm labor, contributing to the generation of uterotonic
      prostaglandins (PGs) known to participate in mammalian parturition. Augmented COX
      activity is highly correlated with increased COX2 (also known as prostaglandin
      endoperoxide synthase 2, PTGS2) gene expression. We and others have demonstrated
      an essential role for nuclear factor kappaB (NFkappaB) in cytokine-driven COX2
      expression. Peroxisome proliferator-activated receptor gamma (PPARG), a member of
      the nuclear hormone receptor superfamily, has been shown to antagonize NFkappaB
      activation and inflammatory gene expression, including COX2. We hypothesized that
      PPARG activation might suppress COX2 expression during pregnancy. Using primary
      amnion and WISH cells, we evaluated the effects of pharmacological
      (thiazolidinediones) and putative endogenous (15-deoxy-Delta(12,14)-prostaglandin
      J2, 15d-PGJ2) PPARG ligands on cytokine-induced NFkappaB activation, COX2
      expression, and PGE2 production. We observed that COX2 expression and PGE2
      production induced by tumor necrosis factor alpha (TNF) were significantly
      abrogated by 15d-PGJ2. The thiazolidinediones rosiglitazone (ROSI) and
      troglitazone (TRO) had relatively little effect on cytokine-induced COX2
      expression except at high concentrations, at which these agents tended to
      increase COX2 abundance relative to cells treated with TNF alone. Interestingly,
      treatment with ROSI, but not TRO, led to augmentation of TNF-stimulated PGE2
      production. Mechanistically, we observed that 15d-PGJ2 markedly diminished
      cytokine-induced activity of the NFkappaB transcription factor, whereas
      thiazolidinediones had no discernable effect on this system. Our data suggest
      that pharmacological and endogenous PPARG ligands use both receptor-dependent and
      -independent mechanisms to influence COX2 expression.

PMID- 15843498
TI  - Xrcc3 induces cisplatin resistance by stimulation of Rad51-related
      recombinational repair, S-phase checkpoint activation, and reduced apoptosis.
AB  - Eukaryotic cells respond to DNA damage by activation of DNA repair, cell cycle
      arrest, and apoptosis. Several reports suggest that such responses may be
      coordinated by communication between damage repair proteins and proteins
      signaling other cellular responses. The Rad51-guided homologous recombination
      repair system plays an important role in the recognition and repair of DNA
      interstrand crosslinks (ICLs), and cells deficient in this repair pathway become
      hypersensitive to ICL-inducing agents such as cisplatin and melphalan. We
      investigated the possible role of the Rad51-paralog protein Xrcc3 in drug
      resistance. Xrcc3 overexpression in MCF-7 cells resulted in 1) a 2- to 6-fold
      resistance to cisplatin/melphalan, 2) a 2-fold increase in drug-induced Rad51
      foci, 3) an increased cisplatin-induced S-phase arrest, 4) decreased cisplatin
      induced apoptosis, and 5) increased cisplatin-induced DNA synthesis arrest.
      Interestingly, Xrcc3 overexpression did not alter the doubling time or cell cycle
      progression in the absence of DNA damage. Furthermore, Xrcc3 overexpression is
      associated with increased Rad51C protein levels consistent with the known
      interaction of these two proteins. Our results demonstrate that Xrcc3 is an
      important factor in DNA cross-linking drug resistance in human tumor cells and
      suggest that the response of the homologous recombinational repair machinery and
      cell cycle checkpoints to DNA cross-linking agents is intertwined.

PMID- 15843499
TI  - Cigarette smoke extract increases C5a receptor expression in human bronchial
      epithelial cells.
AB  - We have shown that exposing human bronchial epithelial cells (HBECs) to 5%
      cigarette smoke extract (CSE) up-regulates C5a anaphylatoxin receptor (C5aR)
      expression as determined by flow cytometric analysis and immunohistochemistry. In
      this study, we conducted whole-cell saturation studies to quantitate the receptor
      number. After exposing an HBEC line (BEAS-2B) to CSE, radiolabeled C5a bound
      saturably with Kd = 2.71 +/- 1.03 nM (n = 4) and Bmax = 15,044 +/- 5702
      receptors/cells. Without 5% CSE, no C5a binding was detected. Competitive binding
      studies revealed two classes of sites with distinct affinities for C5a (Ki1 =
      3.28 x 10(-16) M; Ki2 = 1.60 x 10(-9) M). BEAS-2Bs were transfected with wild
      type (WT) or mutant dominant-negative (DN) protein kinase C-alpha (PKC-alpha) to
      investigate the relationship between PKC-alpha and C5aR availability and
      affinity. Western blot analysis revealed a 75-kDa lysate band from cells
      expressing WT and DN PKC-alpha, but DN cells exposed to 5% CSE had no functional
      PKC activity. Pretreatment with Go6976 [12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13
      methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole] (PKC-alpha inhibitor) had
      no effect on DN but significantly decreased WT PKC activity. Competitive binding
      studies conducted on either WT or DN PKC-alpha-transfected cells also revealed
      two classes of binding sites for C5a having different affinities. There was a
      significant rightward shift of the binding curve when WT cells were pretreated
      with Go6976. These data suggest that C5aR is detectable on bronchial epithelial
      cells exposed to CSE and that exposure to CSE increases the availability of C5a
      binding sites. The data also indicate that PKC-alpha may play an important role
      in modulating C5aR binding.

PMID- 15843500
TI  - Discriminative stimulus effects of acute morphine followed by naltrexone in the
      squirrel monkey: a further characterization.
AB  - The discriminative stimulus effects of acute morphine followed by naltrexone have
      been described previously in nonhuman primates. The purposes of this study were
      to 1) extend the pharmacological characterization of the discrimination by
      testing mu-opioid agonists other than morphine and opioid-like compounds other
      than naltrexone and 2) to examine further the relationship between agonist
      pretreatment time and manifestation of the cue produced by morphine followed by
      naltrexone. Subjects were trained to discriminate 1.7 mg/kg morphine --> 0.1
      mg/kg naltrexone (MOR --> NTX) versus saline followed by 0.1 mg/kg naltrexone.
      When combined with 0.1 mg/kg naltrexone, all agonists tested, save buprenorphine,
      meperidine, and nalbuphine, produced dose-dependent increases in MOR --> NTX
      appropriate responding, culminating in criterion levels of responding. Comparing
      agonist ED50 values revealed a rank order of potency of etorphine >> fentanyl >>
      levorphanol > heroin > or = methadone > or = nalbuphine > or = morphine. ED50
      values for buprenorphine and meperidine could not be calculated. MOR --> NTX
      appropriate responding after doses of agonist that produced criterion or near
      criterion levels of responding was also a function of naltrexone dose. After
      morphine pretreatment, diprenorphine and nalorphine, but not buprenorphine, dose
      dependently substituted for naltrexone. The MOR --> NTX discrimination also
      depended upon the interval between morphine and NTX administration. Finally, 1-h
      pretreatment with morphine and etorphine, but not buprenorphine, followed by
      naltrexone generalized to 4 h MOR --> NTX. These results suggest a minimum
      efficacy requirement of acutely administered agonists together with the
      naltrexone training dose for stimulus control of behavior. However, in some cases
      this requirement can be overcome with higher doses of naltrexone.

PMID- 15843501
TI  - A macroglomerulus in the antennal lobe of leaf-cutting ant workers and its
      possible functional significance.
AB  - Ants have a well-developed olfactory system, and pheromone communication is
      essential for regulating social life within their colonies. We compared the
      organization of primary olfactory centers (antennal lobes, ALs) in the brain of
      two closely related species of leaf-cutting ants (Atta vollenweideri, Atta
      sexdens). Both species express a striking size polymorphism associated with
      polyethism. We discovered that the ALs of large workers contain a substantially
      enlarged glomerulus (macroglomerulus, MG) at the entrance of the antennal nerve.
      This is the first description of an MG in non-sexual individuals of an insect.
      The location of the MG is laterally reversed in the two species, and workers of
      different size express a disproportional allometry of glomerular volumes. While
      ALs of large workers contain an MG, glomeruli in small workers are all similar in
      size. We further compared electroantennogram (EAG) responses to two common trail
      pheromone components of leaf-cutting ants: 4-methylpyrrol-2-carboxylate and 2
      ethyl-3,6-dimethylpyrazine. At high concentrations the ratio of the EAG signals
      to 2-ethyl-3,6-dimethylpyrazine versus 4-methylpyrrol-2-carboxylate was
      significantly smaller in A. vollenweideri compared with the ratio of EAG signals
      to the same two components in A. sexdens. The differences in EAG signals and the
      species specific MG location in large workers provide correlative evidence that
      the MG may be involved in the detection of the trail pheromone.

PMID- 15843503
TI  - Attentional biases to pain and social threat in children with recurrent abdominal
      pain.
AB  - OBJECTIVES: To test whether children with recurrent abdominal pain (RAP) exhibit
      subliminal (nonconscious) and supraliminal (conscious) attentional biases to pain
      related words, and to determine correlates of these biases. Previous research
      indicates that individuals attend to disorder-relevant threat words, and in this
      study, attentional biases to disorder-relevant threat (pain), alternative threat
      (social threat), and neutral words were compared. METHODS: Participants were 59
      children with RAP who completed a computer-based attentional bias task.
      Participants and their parents also completed questionnaires measuring pain,
      somatic complaints, anxiety/depression, and body vigilance. RESULTS: Children
      with RAP showed attentional biases toward subliminal pain-related words and
      attentional biases away from supraliminal pain-related words. Participants'
      attentional biases to social threat-related words were marginally significant and
      also reflected subliminal attention and supraliminal avoidance. Attentional
      biases were related to parent and child reports of pain, body vigilance, and
      anxiety/depression. CONCLUSIONS: Children with RAP show nonconscious attention to
      and conscious avoidance of threat-related words. Their attentional biases relate
      to individual differences in symptom severity. Implications for models of
      pediatric pain and future studies are discussed.

PMID- 15843502
TI  - Prenatal cocaine exposure and children's language functioning at 6 and 9.5 years:
      moderating effects of child age, birthweight, and gender.
AB  - OBJECTIVE: To evaluate whether prenatal cocaine exposure (PCE), or the
      interaction between PCE and contextual variables, is associated with children's
      language at age 6 and 9.5 years, adjusting for relevant covariates. METHODS:
      Analyses were based on 160 low-income, urban children from a prospective study
      who completed a standardized language assessment at 6 and 9.5 years. PCE was
      determined using neonatal meconium assays and maternal self-report. RESULTS:
      Significant interaction effects of PCE on language outcomes were found in
      multivariate longitudinal analyses using generalized estimating equations (GEE).
      Children with PCE had lower receptive language than unexposed children at 6 but
      not at 9.5 years, lower expressive language if they had lower birthweight, and
      lower expressive and total language if they were female. Other risk (e.g.,
      violence exposure) and protective factors (e.g., preschool experience) were
      related to language outcomes regardless of PCE status. CONCLUSIONS: Age,
      birthweight, and gender moderated the relation between PCE and school-aged
      children's language.

PMID- 15843504
TI  - Dose-dependent modulation of the in vitro cytokine production of human immune
      competent cells by lead salts.
AB  - Lead pollution constitutes a major health problem that has been intensively
      debated. To reveal its effects on the immune response, the influence of lead on
      the in vitro cytokine production of human peripheral mononuclear blood cells was
      investigated. Isolated cells were exposed to lead acetate or lead chloride for 24
      h in the presence of either heat-killed Salmonella enteritidis (hk-SE) or
      monoclonal antibodies (anti-CD3, anti-CD28, anti-CD40) as cell activators. Our
      results showed that while higher lead doses are toxic, lower ones evoke
      immunomodulatory effects. All tested lead doses significantly reduced cell
      vitality and/or proliferation and affected secretion of proinflammatory, T helper
      cell type (T(H))1 and T(H)2 cytokines. Expression of interferon (IFN)-gamma,
      interleukin (IL)-1beta, and tumor necrosis factor (TNF)-alpha was reduced at
      lower lead doses in both models of cell stimulation. Although hk-SE failed to
      induce detectable IL-4 levels, monoclonal antibody-induced IL-4, IL-6, and IL-10
      secretion increased in the presence of lower lead doses. Also, levels of hk-SE
      induced IL-10 and IL-6 secretion were increased at lower lead doses. Thus,
      exposure to lower doses leads to suppression of the T(H)1 cytokine IFN-gamma and
      the proinflammatory cytokines TNF-alpha and IL-1beta. The elevated production of
      IL-4 and/or IL-10 can induce and maintain a T(H)2 immune response and might
      contribute to increased susceptibility to pathologic agents as well as the
      incidence of allergic hypersensitivity and/or T(H)2-dominated autoimmune
      diseases.

PMID- 15843505
TI  - Cytochrome P450 1B1 is required for 7,12-dimethylbenz(a)-anthracene (DMBA)
      induced spleen cell immunotoxicity.
AB  - 7,12-Dimethylbenz(a)anthracene (DMBA) is a potent carcinogen that induces
      immunosuppression of both humoral and cell-mediated immunity in mice and other
      species. Previous studies have shown that CYP1B1 is required for bone marrow
      toxicity produced by DMBA in mice. Therefore, the purpose of these studies was to
      determine whether CYP1B1 was required for spleen cell immunotoxicity. Female
      C57BL/6N wild-type (WT) and CYP1B1 knockout (-/-) mice were treated with 0, 17,
      50, or 150 mg/kg (cumulative dose) DMBA in corn oil by oral gavage once a day for
      five days. Several immunotoxicological assays were used to assess the effects of
      DMBA on systemic immunity. These included the in vitro T-dependent antibody
      response to sheep red blood cells (SRBC) measured using a direct plaque forming
      cell (PFC) assay, T- and B-cell mitogenesis induced by Con A and LPS, and
      nonspecific cell-mediated immunity was evaluated using an NK cytotoxicity assay.
      In addition, lymphocyte subpopulations were measured by flow cytometry using
      specific cell surface markers. Following five days of DMBA treatment, the body
      weights and spleen cell surface markers of the WT and CYP1B1 (-/-) mice showed no
      significant changes. A decrease in NK activity was found at the 50 mg/kg DMBA
      dose in WT mice, but not in the CYP1B1 (-/-) mice. Interestingly, at the 150
      mg/kg dose of DMBA, CYP1B1 null mice had decreased NK activity, whereas WT mice
      did not. The SRBC PFC response demonstrated that the IgM antibody response was
      suppressed by DMBA in WT mice in a dose-dependent manner (significant at 50 and
      150 mg/kg). However, there were no changes in the SRBC PFC responses in any DMBA
      test group in the CYP1B1 (-/-) mice. Similarly, while DMBA suppressed B- and T
      cell mitogenesis at the 50 and 150 mg/kg dose levels in C57BL/6N WT mice, no
      effect was seen in CYP1B1 (-/-) mice. Thus, CYP1B1 appears to be critical for the
      immunosuppression of DMBA in mice, suggesting a role for bioreactive metabolites
      in the spleen cell immunotoxicity produced by DMBA.

PMID- 15843506
TI  - Effects of thimerosal on NGF signal transduction and cell death in neuroblastoma
      cells.
AB  - Signaling through neurotrophic receptors is necessary for differentiation and
      survival of the developing nervous system. The present study examined the effects
      of the organic mercury compound thimerosal on nerve growth factor signal
      transduction and cell death in a human neuroblastoma cell line (SH-SY5Y cells).
      Following exposure to 100 ng/ml NGF and increasing concentrations of thimerosal
      (1 nM-10 microM), we measured the activation of TrkA, MAPK, and PKC-delta. In
      controls, the activation of TrkA MAPK and PKC-delta peaked after 5 min of
      exposure to NGF and then decreased but was still detectable at 60 min. Concurrent
      exposure to increasing concentrations of thimerosal and NGF for 5 min resulted in
      a concentration-dependent decrease in TrkA and MAPK phosphorylation, which was
      evident at 50 nM for TrkA and 100 nM for MAPK. Cell viability was assessed by the
      LDH assay. Following 24-h exposure to increasing concentrations of thimerosal,
      the EC50 for cell death in the presence or absence of NGF was 596 nM and 38.7 nM,
      respectively. Following 48-h exposure to increasing concentrations of thimerosal,
      the EC50 for cell death in the presence and absence of NGF was 105 nM and 4.35
      nM, respectively. This suggests that NGF provides protection against thimerosal
      cytotoxicity. To determine if apoptotic versus necrotic cell death was occurring,
      oligonucleosomal fragmented DNA was quantified by ELISA. Control levels of
      fragmented DNA were similar in both the presence and absence of NGF. With and
      without NGF, thimerosal caused elevated levels of fragmented DNA appearing at
      0.01 microM (apoptosis) to decrease at concentrations >1 microM (necrosis). These
      data demonstrate that thimerosal could alter NGF-induced signaling in
      neurotrophin-treated cells at concentrations lower than those responsible for
      cell death.

PMID- 15843507
TI  - Coplanar PCB congeners increase uterine weight and frontal cortical dopamine in
      the developing rat: implications for developmental neurotoxicity.
AB  - We show that developmental exposure of the laboratory rat to the coplanar
      polychlorinated biphenyl (PCB) congener 3,4,3',4'-tetrachlorobiphenyl (TCB) and
      the structurally similar congener 3,4,5,3',4'-pentachlorobiphenyl (PtCB) elevates
      dopamine (DA) concentrations in the prefrontal cortex (PFC). To determine whether
      these coplanar congeners are estrogenic, and may thus contribute to the
      elevations in PFC DA, we measured uterine wet weight (UWW) in prepubertal rats
      exposed to TCB or PtCB. For comparison, additional animals were exposed to either
      the ortho-substituted congener 2,4,2',4'-tetrachlorobiphenyl (o-TCB) or
      3,4,5,3',4',5'-hexachlorobiphenyl (HCB), a coplanar congener highly resistant to
      metabolism. Both TCB and PtCB increased UWW, but this effect was blocked after
      exposure to the anti-estrogen ICI 182,780. Neither o-TCB nor HCB altered UWW.
      These results demonstrate that certain coplanar PCB congeners and/or their
      metabolites, are estrogenic, and suggest that exposure during critical periods of
      neuronal development may increase central DA concentrations, and by inference,
      alter behavior.

PMID- 15843508
TI  - Promotion of thyroid carcinogenesis by para-aminobenzoic acid in rats initiated
      with N-bis(2-hydroxypropyl)nitrosamine.
AB  - Sulfonamide analogues of para-aminobenzoic acid (PABA), a precursor of folate
      synthesis, have beneficial effects as antifolate, but thyroid peroxidase
      inhibition has been reported as a side effect that results in promotion of rat
      thyroid carcinogenesis. In the present study, effects of PABA itself on F344 rat
      thyroid carcinogenesis after initiation with N-bis(2-hydroxypropyl)nitrosamine
      (DHPN) were evaluated. In experiment 1, rats in groups 1-4 received a single
      subcutaneous injection of DHPN at 2800 mg/kg, and groups 5 and 6 received vehicle
      saline alone. From 1 week after DHPN initiation, rats in groups 2, 3, 4, and 6
      were fed basal diet containing 0.25%, 0.5%, 1.0%, and 1.0% PABA, respectively,
      for 40 weeks. Rats in groups 1 and 5 received basal diet alone throughout the
      experiment. The final incidence of thyroid follicular cell adenomas and
      adenocarcinomas was significantly (p < 0.05 or 0.01) increased in groups 3 and 4
      as compared to group 1. No thyroid tumors were found in groups 5 and 6. In
      experiment 2, animals in group 1 were fed basal diet alone, while groups 2 and 3
      were given 0.5% and 1.0% PABA in the diet, respectively, for 2 weeks. Thyroid
      weights in group 3, and serum thyroid stimulating hormone level and proliferative
      activity of follicular cells in groups 2 and 3 were significantly (p < 0.05 or
      0.01) elevated. In addition, the serum thyroxine level in group 3 was
      significantly (p < 0.05) depressed. These results clearly indicate that PABA
      exerts promotion/progression effects on rat thyroid carcinogenesis as a result of
      hypothyroidism followed by negative-feedback via the thyroid-pituitary axis.

PMID- 15843509
TI  - Evaluating deaf students' readiness to meet the English language and literacy
      demands of postsecondary educational programs.
AB  - The purpose of this study was to investigate alternative methods for evaluating
      deaf students' readiness to meet the English language and literacy demands of
      postsecondary educational programs. In the first part of the study, scores
      obtained by a large sample of deaf students on the ACT Assessment (ACT Composite
      score and scores on the ACT English and Reading tests) were compared to their
      scores on various measures of English language and literacy skills. In the second
      part of the study, the performance of a smaller sample of deaf students on the
      ESL Reading and ESL Grammar/Usage components of COMPASS/ESL was compared to their
      performance on a set of concurrent measures of English skills. The results of
      this investigation demonstrate that neither the ACT Assessment nor COMPASS/ESL
      are appropriate for the full range of deaf students seeking admission to
      postsecondary educational programs. However, the ACT Assessment is appropriate
      for deaf students seeking admission to transferable (BS and AAS) degree programs,
      and the ESL Reading and Grammar/Usage tests appear to be appropriate for deaf
      students seeking admission to nontransferable (AOS) degree programs. Taken
      together, the combination of the ACT Assessment and COMPASS/ESL appear able to
      provide a valid, reliable, and coherent approach to admissions screening
      assessment for the full range of deaf students seeking admission to postsecondary
      programs.

PMID- 15843510
TI  - Crossing the threshold of lymphocyte activation.

PMID- 15843511
TI  - The mechanism of antigenic stimulation of primary and secondary clonal precursor
      cells. 1972.

PMID- 15843512
TI  - An integral role for heme oxygenase-1 and carbon monoxide in maintaining
      peripheral tolerance by CD4+CD25+ regulatory T cells.
AB  - Over the past decade, a great deal of interest and attention has been directed
      toward a population of regulatory T cells (Treg) coexpressing the markers CD4 and
      CD25. The hallmark phenotype of this cell population resides in its ability to
      dominantly maintain peripheral tolerance and avert autoimmunity. Despite robust
      research interest in Treg, their mechanism of action and interaction with other
      cell populations providing immune regulation remains unclear. In this study, we
      present a model for Treg activity that implicates carbon monoxide, a by-product
      of heme oxygenase-1 activity, as an important and underappreciated facet in the
      suppressive capacity of Treg. Our hypothesis is based on recent evidence
      supporting a role for heme oxygenase-1 in regulating immune reactivity and posit
      carbon monoxide to function as a suppressive molecule. Potential roles for
      indoleamine 2,3-dioxygenase, costimulatory molecules, and cytokines in tolerance
      induction are also presented. This model, if validated, could act as a catalyst
      for new investigations into Treg function and ultimately result in novel methods
      to modulate Treg biology toward therapeutic applications.

PMID- 15843513
TI  - Cutting edge: in vivo blockade of human IL-2 receptor induces expansion of
      CD56(bright) regulatory NK cells in patients with active uveitis.
AB  - In vivo blockade of the human IL-2R by mAb has been used for immunosuppression in
      transplantation, therapy for leukemia, and autoimmune diseases. In this study, we
      report that administration of a humanized IL-2R blocking Ab induced a 4- to 20
      fold expansion of CD56(bright) regulatory NK cells in uveitis patients over time.
      The induced CD56(bright) regulatory NK cells from patients exhibited similar
      phenotype as those naturally occurring CD56(bright) cells. Patients with active
      uveitis had a significantly lower level of CD56(bright) NK cells compared with
      normal donors (p < 0.01). In addition, the induced CD56(bright) cells could
      secrete large amounts of IL-10 whereas CD56(dim) NK cells could not, suggesting
      that the induction of the CD56(bright) cells may have a beneficial effect on the
      remission of active uveitis. Our observation may have implications to IL-2R
      blockade therapy and for the potential role of CD56(bright) regulatory NK cells
      in autoimmune diseases.

PMID- 15843514
TI  - Inhibitors of TLR-9 act on multiple cell subsets in mouse and man in vitro and
      prevent death in vivo from systemic inflammation.
AB  - In parallel with the discovery of the immunostimulatory activities of CpG
      containing oligodeoxynucleotides, several groups have reported specific DNA
      sequences that could inhibit activation by CpG-containing oligodeoxynucleotides
      in mouse models. We show that these inhibitory sequences, termed IRS, inhibit TLR
      9-mediated activation in human as well as mouse cells. This inhibitory activity
      includes proliferation and IL-6 production by B cells, and IFN-alpha and IL-12
      production by plasmacytoid dendritic cells. Our studies of multiple cell types in
      both mice and humans show the optimal IRS to contain a GGGG motif within the
      sequence, and the activity to require a phosphorothioate backbone. Although the
      GGGG motif readily itself leads to formation of a tetrameric oligodeoxynucleotide
      structure, inhibitory activity resides exclusively in the single-stranded form.
      When coinjected with a CpG oligodeoxynucleotide in vivo, IRS were shown to
      inhibit inflammation through a reduction in serum cytokine responses. IRS do not
      need to be injected at the same site to inhibit, demonstrating that rapid,
      systemic inhibition of TLR-9 can be readily achieved. IRS can also inhibit a
      complex pathological response to ISS, as shown by protection from death after
      massive systemic inflammation induced by a CpG-containing oligodeoxynucleotides.

PMID- 15843515
TI  - An essential role for phospholipase D in the activation of protein kinase C and
      degranulation in mast cells.
AB  - Activation of phospholipase D (PLD) and protein kinase C (PKC) as well as calcium
      mobilization are essential signals for degranulation of mast cells. However, the
      exact role of PLD in degranulation remains undefined. In this study we have
      tested the hypothesis that the PLD product, phosphatidic acid, and
      diacylglycerides generated therefrom might promote activation of PKC. Studies
      were conducted in two rodent mast cell lines that were stimulated with Ag via
      FcepsilonRI and a pharmacologic agent, thapsigargin. Diversion of production of
      phosphatidic acid to phosphatidylbutanol (the transphosphatidylation reaction) by
      addition of l-butanol suppressed both the translocation of diacylglyceride
      dependent isoforms of PKC to the membrane and degranulation. Tertiary-butanol,
      which is not a substrate for the transphosphatidylation, had a minimal effect on
      PKC translocation and degranulation, and 1-butanol itself had no effect on PKC
      translocation when PKC was stimulated directly with phorbol ester, 12-O
      tetradecanoylphorbol-13-acetate. Also, in cells transfected with small inhibitory
      RNAs directed against PLD1 and PLD2, activation of PLD, generation of
      diacylglycerides, translocation of PKC, and degranulation were all suppressed.
      Phorbol ester, which did not stimulate degranulation by itself, restored
      degranulation when used in combination with thapsigargin whether PLD function was
      disrupted with 1-butanol or the small inhibitory RNAs. However, degranulation was
      not restored when cells were costimulated with Ag and phorbol ester. These
      results suggested that the production of phosphatidic acid by PLD facilitates
      activation of PKC and, in turn, degranulation, although additional PLD-dependent
      processes appear to be critical for Ag-mediated degranulation.

PMID- 15843516
TI  - Mycobacterium tuberculosis heat shock fusion protein enhances class I MHC cross
      processing and -presentation by B lymphocytes.
AB  - Exogenous heat shock protein (HSP):peptide complexes are processed for cross
      presentation of HSP-chaperoned peptides on class I MHC (MHC-I) molecules. Fusion
      proteins containing HSP and Ag sequences facilitate MHC-I cross-presentation of
      linked antigenic epitopes. Processing of HSP-associated Ag has been attributed to
      dendritic cells and macrophages. We now provide the first evidence to show
      processing of HSP-associated Ag for MHC-I cross-presentation by B lymphocytes.
      Fusion of OVA sequence (rOVA, containing OVA(230-359) sequence) to Mycobacterium
      tuberculosis HSP70 greatly enhanced rOVA processing and MHC-I cross-presentation
      of OVA(257-264):K(b) complexes by B cells. Enhanced processing was dependent on
      linkage of rOVA sequence to HSP70. M. tuberculosis HSP70-OVA fusion protein
      enhanced cross-processing by a CD91-dependent process that was independent of
      TLR4 and MyD88. The enhancement occurred through a post-Golgi, proteasome
      independent mechanism. These results indicate that HSPs enhance delivery and
      cross-processing of HSP-linked Ag by B cells, which could provide a novel
      contribution to the generation of CD8(+) T cell responses. HSP fusion proteins
      have potential advantages for use in vaccines to enhance priming of CD8(+) T cell
      responses.

PMID- 15843517
TI  - TGF-beta 1 attenuates the acquisition and expression of effector function by
      tumor antigen-specific human memory CD8 T cells.
AB  - TGF-beta1 is a potent immunoregulatory cytokine. However, its impact on the
      generation and effector function of Ag-specific human effector memory CD8 T cells
      had not been evaluated. Using Ag-specific CD8 T cells derived from melanoma
      patients immunized with the gp100 melanoma Ag, we demonstrate that the addition
      of TGF-beta1 to the initial Ag activation cultures attenuated the gain of
      effector function by Ag-specific memory CD8 T cells while the phenotypic changes
      associated with activation and differentiation into effector memory were
      comparable to control cultures. These activated memory CD8 T cells consistently
      expressed lower mRNA levels for T-bet, suggesting a mechanism for TGF-beta1
      mediated suppression of gain of effector function in memory T cells. Moreover,
      TGF-beta1 induced a modest expression of CCR7 on Ag-activated memory CD8 T cells.
      TGF-beta1 also suppressed cytokine secretion by Ag-specific effector memory CD8 T
      cells, as well as melanoma-reactive tumor-infiltrating lymphocytes and CD8 T cell
      clones. These results demonstrate that TGF-beta1 suppresses not only the
      acquisition but also expression of effector function on human memory CD8 T cells
      and tumor-infiltrating lymphocytes reactive against melanoma, suggesting that TGF
      beta1-mediated suppression can hinder the therapeutic benefits of vaccination, as
      well as immunotherapy in cancer patients.

PMID- 15843518
TI  - Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates
      chemotaxis in human monocyte-derived dendritic cells.
AB  - There is increasing evidence that histamine as an important mediator of immediate
      type allergic reactions also effects professional APCs. Recent reports showed
      effects of histamine on human monocyte-derived dendritic cells (MoDC) mediated
      primarily via histamine H1 receptors (H1R) and H2R. We show here that MoDC also
      express H3R and H4R at the mRNA and protein level. mRNA of the H3R is down
      regulated and mRNA of the H4R is up-regulated during the differentiation from
      monocytes to MoDC. H4R or H2R stimulation suppressed IL-12p70 production in MoDC.
      Induction of cAMP was necessary for IL-12p70 inhibition mediated via the H2R. In
      contrast, H4R stimulation did not affect cAMP production but induced the
      transcription factor AP-1, and U0126, an inhibitor of AP-1 transactivation and
      MEK, rescued H4R mediated IL-12p70 suppression. Moreover, MoDC responded to a H4R
      agonist (and also to a H2R agonist) with increased F-actin polymerization and
      migration in modified Boyden chamber assays, suggesting a chemotactic effect of
      histamine via the H2R and the H4R. Thus, H4R stimulation on MoDC results in
      immunomodulatory and chemotactic effects. Histamine induces chemotaxis and IL
      12p70 suppression via different receptors using different signaling pathways,
      which might be important for the pathogenesis of and therapeutic interventions in
      allergic diseases.

PMID- 15843519
TI  - B lymphocytes participate in cross-presentation of antigen following gene gun
      vaccination.
AB  - Although endocytosed proteins are commonly presented via the class II MHC pathway
      to stimulate CD4(+) T cells, professional APCs can also cross-present Ags,
      whereby these exogenous peptides can be complexed with class I MHC for cross
      priming of CD8(+) T cells. Whereas the ability of dendritic cells (DCs) to cross
      present Ags is well documented, it is not known whether other APCs may also play
      a role, or what is the relative contribution of cross-priming to the induction of
      acquired immunity after DNA immunization. In this study, we compared immune
      responses generated after gene gun vaccination of mice with DNA vaccine plasmids
      driven by the conventional CMV promoter, the DC-specific CD11c promoter, or the
      keratinocyte-specific K14 promoter. The CD11c promoter achieved equivalent
      expression in CD11c(+) DCs in draining lymph nodes over time, as did a
      conventional CMV-driven plasmid. However, immunization with DC-restricted DNA
      vaccines failed to generate protective humoral or cellular immunity to model Ags
      influenza hemagglutinin and OVA, despite the ability of CD11c(+) cells isolated
      from lymph nodes to stimulate proliferation of Ag-specific T cells directly ex
      vivo. In contrast, keratinocyte-restricted vaccines elicited comparable T and B
      cell activity as conventional CMV promoter-driven vaccines, indicating that cross
      priming plays a major role in the generation of immune responses after gene gun
      immunization. Furthermore, parallel studies in B cell-deficient mu-MT mice
      demonstrated that B lymphocytes, in addition to DCs, mediate cross-priming of Ag
      specific T cells. Collectively, these data indicate that broad expression of the
      immunogen is required for optimal induction of protective acquired immunity.

PMID- 15843520
TI  - Granulysin, a cytolytic molecule, is also a chemoattractant and proinflammatory
      activator.
AB  - Granulysin, a cationic protein produced by activated human CTL and NK cells, is
      cytolytic against microbial and tumor targets. In this study we show that
      granulysin also functions as a chemoattractant and activates monocytes to produce
      cytokines/chemokines. Although granulysin-mediated cytotoxicity occurs at
      micromolar concentrations, chemoattraction occurs in the nanomolar range, and
      immune activation occurs over a wide range of concentrations (nanomolar to
      micromolar). Granulysin causes a 2- to 7-fold increase in chemotaxis of
      monocytes, CD4(+), and CD8(+) memory (CD45RO) but not naive (CD45RA) T cells, NK
      cells, and mature, but not immature, monocyte-derived dendritic cells. Pertussis
      toxin treatment abrogates chemoattraction by granulysin, indicating involvement
      of G-protein-coupled receptor(s). At low concentrations (10 nM), granulysin
      promotes a 3- to 10-fold increase in MCP-1 and RANTES produced by monocytes and
      U937 cells, while a 2-fold increase in TNF-alpha production by LPS-stimulated
      monocytes requires higher concentrations of granulysin (micromolar). Taken
      together, these data indicate that the local concentration of granulysin is
      critical for the biologic activity, with high concentrations resulting in
      cytotoxicity while lower concentrations, presumably further from the site of
      granulysin release, actively recruit immune cells to sites of inflammation.

PMID- 15843521
TI  - HIV-1 trans-activator of transcription substitutes for oxidative signaling in
      activation-induced T cell death.
AB  - Termination of an immune response requires elimination of activated T lymphocytes
      by activation-induced cell death (AICD). In AICD, CD95 (Apo-1/Fas) ligand (L)
      triggers apoptosis of CD95-positive activated T lymphocytes. In AIDS patients,
      AICD is strongly enhanced and accelerated. We and others have previously shown
      that HIV-1 trans-activator of transcription (HIV-1 Tat) sensitizes T cells toward
      CD95-mediated apoptosis and up-regulates CD95L expression by affecting the
      cellular redox balance. In this study, we show that it is hydrogen peroxide
      (H(2)O(2)) that functions as an essential second messenger in TCR signaling. The
      H(2)O(2) signal combined with simultaneous calcium (Ca(2+)) influx into the
      cytosol constitutes the minimal requirement for induction of CD95L expression.
      Either signal alone is insufficient. We further show that HIV-1 Tat interferes
      with TCR signaling and induces a H(2)O(2) signal. H(2)O(2) generated by HIV-1 Tat
      combines with CD4-dependent calcium influx and causes massive T cell apoptosis.
      Thus, our data provide an explanation for CD4(+) T lymphocyte depletion during
      progression of AIDS.

PMID- 15843522
TI  - IL-2 increases human telomerase reverse transcriptase activity transcriptionally
      and posttranslationally through phosphatidylinositol 3'-kinase/Akt, heat shock
      protein 90, and mammalian target of rapamycin in transformed NK cells.
AB  - Human telomerase activity is induced by Ag receptor ligation in T and B cells.
      However, it is unknown whether telomerase activity is increased in association
      with activation and proliferation of NK cells. We found that telomerase activity
      in a human NK cell line (NK-92), which requires IL-2 for proliferation, was
      increased within 24 h after stimulation with IL-2. Levels of human telomerase
      reverse transcriptase (hTERT) mRNA and protein correlated with telomerase
      activity. ERK1/2 and Akt kinase (Akt) were activated by IL-2 stimulation.
      LY294002, an inhibitor of PI3K, abolished expression of hTERT mRNA and protein
      expression and abolished hTERT activity, whereas PD98059, which inhibits MEK1/2
      and thus ERK1/2, had no effect. In addition, radicicol, an inhibitor of heat
      shock protein 90 (Hsp90), and rapamycin, an inhibitor of the mammalian target of
      rapamycin (mTOR), blocked IL-2-induced hTERT activity and nuclear translocation
      of hTERT but not hTERT mRNA expression. hTERT was coimmunoprecipitated with Akt,
      Hsp90, mTOR, and p70 S6 kinase (S6K), suggesting that these molecules form a
      physical complex. Immunoprecipitates of Akt, Hsp90, mTOR, and S6K from IL-2
      stimulated NK-92 cells contained telomerase activity. Furthermore, the findings
      that Hsp90 and mTOR immunoprecipitates from primary samples contained telomerase
      activity are consistent with the results from NK-92 cells. These results indicate
      that IL-2 stimulation induces hTERT activation and that the mechanism of IL-2
      induced hTERT activation involves transcriptional or posttranslational regulation
      through the pathway including PI3K/Akt, Hsp90, mTOR, and S6K in NK cells.

PMID- 15843523
TI  - Cellular FLIP (long form) regulates CD8+ T cell activation through caspase-8
      dependent NF-kappa B activation.
AB  - Cellular FLIP long form (c-FLIP(L)) was originally identified as an inhibitor of
      Fas (CD95/Apo-1). Subsequently, additional functions of c-FLIP(L) were identified
      through its association with receptor-interacting protein (RIP)1 and TNFR
      associated factor 2 to activate NF-kappaB, as well as by its association with and
      activation of caspase-8. T cells from c-FLIP(L)-transgenic (Tg) mice manifest
      hyperproliferation upon activation, although it was not clear which of the
      various functions of c-FLIP(L) was involved. We have further explored the effect
      of c-FLIP(L) on CD8(+) effector T cell function and its mechanism of action. c
      FLIP(L)-Tg CD8(+) T cells have increased proliferation and IL-2 responsiveness to
      cognate Ags as well as to low-affinity Ag variants, due to increased CD25
      expression. They also have a T cytotoxic 2 cytokine phenotype. c-FLIP(L)-Tg
      CD8(+) T cells manifest greater caspase activity and NF-kappaB activity upon
      activation. Both augmented proliferation and CD25 expression are blocked by
      caspase inhibition. c-FLIP(L) itself is a substrate of the caspase activity in
      effector T cells, being cleaved to a p43(FLIP) form. p43(FLIP) more efficiently
      recruits RIP1 than full-length c-FLIP(L) to activate NF-kappaB. c-FLIP(L) and
      RIP1 also coimmunoprecipitate with active caspase-8 in effector CD8(+) T cells.
      Thus, one mechanism by which c-FLIP(L) influences effector T cell function is
      through its activation of caspase-8, which in turn cleaves c-FLIP(L) to allow
      RIP1 recruitment and NF-kappaB activation. This provides a partial explanation of
      why caspase activity is required to initiate proliferation of resting T cells.

PMID- 15843524
TI  - Fc gamma RIIB regulates nasal and oral tolerance: a role for dendritic cells.
AB  - Mucosal tolerance prevents the body from eliciting productive immune responses
      against harmless Ags that enter the body via the mucosae, and is mediated by the
      induction of regulatory T cells that differentiate in the mucosa-draining lymph
      nodes (LN) under defined conditions of Ag presentation. In this study, we show
      that mice deficient in FcgammaRIIB failed to develop mucosal tolerance to OVA,
      and demonstrate in vitro and in vivo a critical role for this receptor in
      modulating the Ag-presenting capacity of dendritic cells (DC). In vitro it was
      shown that absence of FcgammaRIIB under tolerogenic conditions led to increased
      IgG-induced release of inflammatory cytokines such as MCP-1, TNF-alpha, and IL-6
      by bone marrow-derived DC, and increased their expression of costimulatory
      molecules, resulting in an altered immunogenic T cell response associated with
      increased IL-2 and IFN-gamma secretion. In vivo we could show enhanced LN-DC
      activation and increased numbers of Ag-specific IFN-gamma-producing T cells when
      FcgammaRIIB(-/-) mice were treated with OVA via the nasal mucosa, inferring that
      DC modulation by FcgammaRIIB directed the phenotype of the T cell response.
      Adoptive transfer of CD4(+) T cells from the spleen of FcgammaRIIB(-/-) mice to
      naive acceptor mice demonstrated that OVA-responding T cells failed to
      differentiate into regulatory T cells, explaining the lack of tolerance in these
      mice. Our findings demonstrate that signaling via FcgammaRIIB on DC, initiated by
      local IgG in the mucosa-draining LN, down-regulates DC activation induced by
      nasally applied Ag, resulting in those defined conditions of Ag presentation that
      lead to Tr induction and tolerance.

PMID- 15843525
TI  - A novel E3 ubiquitin ligase TRAC-1 positively regulates T cell activation.
AB  - TRAC-1 (T cell RING (really interesting new gene) protein identified in
      activation screen) is a novel E3 ubiquitin ligase identified from a retroviral
      vector-based T cell surface activation marker screen. The C-terminal truncated
      TRAC-1 specifically inhibited anti-TCR-mediated CD69 up-regulation in Jurkat
      cells, a human T leukemic cell line. In this study, we show that TRAC-1 is a RING
      finger ubiquitin E3 ligase with highest expression in lymphoid tissues. Point
      mutations that disrupt the Zn(2+)-chelating ability of its amino-terminal RING
      finger domain abolished TRAC-1's ligase activity and the dominant inhibitory
      effect of C-terminal truncated TRAC-1 on TCR stimulation. The results of in vitro
      biochemical studies indicate that TRAC-1 can stimulate the formation of both K48-
      and K63-linked polyubiquitin chains and therefore could potentially activate both
      degradative and regulatory ubiquitin-dependent pathways. Antisense
      oligonucleotides to TRAC-1 specifically reduced TRAC-1 mRNA levels in Jurkat and
      primary T cells and inhibited their activation in response to TCR cross-linking.
      Collectively, these results indicate that the E3 ubiquitin ligase TRAC-1
      functions as a positive regulator of T cell activation.

PMID- 15843526
TI  - An important role of CD80/CD86-CTLA-4 signaling during photocarcinogenesis in
      mice.
AB  - Although previous studies have shown that altered B7 costimulation plays a
      critical role in UV irradiation-induced regulation of immunity, the individual
      roles of the B7 receptors (CD28 and CTLA-4) or the B7 family members (CD80 and
      CD86) have not been explored. Thus, we investigated CTLA-4 signaling during
      photocarcinogenesis of chronically UV-B-exposed mice using an antagonistic anti
      CTLA-4 Ab. Anti-CTLA-4-treated mice developed significantly fewer UV-induced
      tumors. Moreover, anti-CTLA-4 treatment induced long-lasting protective immunity
      because progressively growing UV tumors inoculated into anti-CTLA-4- and UV
      treated mice that had not developed tumors were rejected. Next, we used mice
      deficient for CD80, CD86, or both in photocarcinogenesis studies to assess the
      relative contributions of these CTLA-4 ligands. Double-deficient mice showed
      significantly reduced UV-induced skin tumor development, whereas CD86(-/-) mice
      produced skin cancer earlier compared with CD80(-/-) and control mice. The growth
      of UV-induced tumors appears to be controlled by UV-induced suppressor T cells,
      because CD80(-/-)/CD86(-/-) mice had strongly reduced numbers of UV-induced
      CD4(+)CD25(+) suppressor T cells. In vitro, CTLA-4 blockade inhibited the
      suppressor activity of UV-induced CD4(+)CD25(+) T cells, suggesting that reduced
      photocarcinogenesis might be due to decreased numbers or function of suppressor T
      cells. Together, these data indicate that blocking CD80/86-CTLA-4 signaling
      induced immune protection against the development of UV-induced skin tumors.
      Furthermore, CD86-mediated costimulation appears to play a more critical role in
      the protection against photocarcinogenesis than CD80.

PMID- 15843527
TI  - Identification of CD4+ T cell-specific epitopes of islet-specific glucose-6
      phosphatase catalytic subunit-related protein: a novel beta cell autoantigen in
      type 1 diabetes.
AB  - Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) has
      been identified as a novel CD8(+) T cell-specific autoantigen in NOD mice. This
      study was undertaken to identify MHC class II-specific CD4(+) T cell epitopes of
      IGRP. Peptides named P1, P2, P3, P4, P5, P6, and P7 were synthesized by aligning
      the IGRP protein amino acid sequence with peptide-binding motifs of the NOD MHC
      class II (I-A(g7)) molecule. Peptides P1, P2, P3, and P7 were immunogenic and
      induced both spontaneous and primed responses. IGRP peptides P1-, P2-, P3-, and
      P7-induced responses were inhibited by the addition of anti-MHC class II (I
      A(g7)) Ab, confirming that the response is indeed I-A(g7) restricted. Experiments
      using purified CD4(+) and CD8(+) T cells from IGRP peptide-primed mice also
      showed a predominant CD4(+) T cell response with no significant activation of
      CD8(+) T cells. T cells from P1-, P3-, and P7-primed mice secreted both IFN-gamma
      and IL-10 cytokines, whereas P2-primed cells secreted only IFN-gamma. Peptides P3
      and P7 prevented the development of spontaneous diabetes and delayed adoptive
      transfer of diabetes. Peptides P1 and P2 delayed the onset of diabetes in both
      these models. In summary, we have identified two I-A(g7)-restricted CD4(+) T cell
      epitopes of IGRP that can modulate and prevent the development of diabetes in NOD
      mice. These results provide the first evidence on the role of IGRP-specific, MHC
      class II-restricted CD4(+) T cells in disease protection and may help in the
      development of novel therapies for type 1 diabetes.

PMID- 15843528
TI  - A major role for memory CD4 T cells in the control of lymphopenia-induced
      proliferation of naive CD4 T cells.
AB  - In a state of lymphopenia, naive and memory CD4 T cells compete with each other
      for expansion at the expense of naive T cells. This competition prevents the
      proliferation as well as the phenotypic and functional conversion of naive T
      cells to "memory-like" T cells and may consequently prevent immune pathology
      frequently associated with lymphopenia-induced proliferation of naive cells.
      However, in T cell replete mice, memory T cells do not compete with naive T
      cells, indicating independent homeostatic control of naive and memory CD4 T cells
      in conditions that do not involve profound lymphopenia. Moreover, within the
      memory compartment, subsequent generation of new memory T cells precludes the
      survival of memory-like T cells. Thus, memory T cells have a major role in the
      control of lymphopenia-induced proliferation of naive cells because they inhibit
      both the generation of memory-like T cells and their persistence within the
      memory compartment.

PMID- 15843529
TI  - Overexpression of IFN-induced protein 10 and its receptor CXCR3 in myasthenia
      gravis.
AB  - Myasthenia gravis (MG) and its animal model, experimental autoimmune MG (EAMG),
      are autoimmune disorders in which the acetylcholine receptor (AChR) is the major
      autoantigen. Microarray technology was used to identify new potential drug
      targets for treatment of myasthenia that would reduce the need for the currently
      used nonspecific immunosuppression. The chemokine IFN-gamma-inducible protein 10
      (IP-10; CXCL10), a CXC chemokine, and its receptor, CXCR3, were found to be
      overexpressed in lymph node cells of EAMG rats. Quantitative real-time PCR
      confirmed these findings and revealed up-regulated mRNA levels of another
      chemoattractant that activates CXCR3, monokine induced by IFN-gamma (Mig; CXCL9).
      TNF-alpha and IL-1beta, which act synergistically with IFN-gamma to induce IP-10,
      were also up-regulated. These up-regulations were observed in immune response
      effector cells, namely, lymph node cells, and in the target organ of the
      autoimmune attack, the muscle of myasthenic rats, and were significantly reduced
      after suppression of EAMG by mucosal tolerance induction with an AChR fragment.
      The relevance of IP-10/CXCR3 signaling in myasthenia was validated by similar
      observations in MG patients. A significant increase in IP-10 and CXCR3 mRNA
      levels in both thymus and muscle was observed in myasthenic patients compared
      with age-matched controls. CXCR3 expression in PBMC of MG patients was markedly
      increased in CD4(+), but not in CD8(+), T cells or in CD19(+) B cells. Our
      results demonstrate a positive association of IP-10/CXCR3 signaling with the
      pathogenesis of EAMG in rats as well as in human MG patients.

PMID- 15843530
TI  - Frequency, specificity, and sites of expansion of CD8+ T cells during primary
      pulmonary influenza virus infection.
AB  - We have used intracellular cytokine staining and MHC class I tetramer binding in
      conjunction with granzyme B protease expression and in vivo BrdU uptake to
      characterize the primary murine CD8(+) T cell response to pulmonary influenza
      virus infection. We have observed that the majority (>90%) of the CD8(+) T cell
      response to the A/Japan/305/57 virus in the lung at the peak of the response
      (days 9-11) is directed to four epitopes (three dominant and one subdominant).
      Using induction of granzyme B as a surrogate to identify specific activated
      CD8(+) T cells, we found that an unexpectedly large fraction ( approximately 70%)
      of lung-infiltrating CD8(+) T cells expressed granzyme B on day 6 of infection
      when estimates by MHC tetramer/intracellular cytokine staining yielded
      substantially lower frequencies ( approximately 30%). In addition, by using
      intranasal administration of BrdU during infection, we obtained evidence for
      proliferative expansion of activated CD8(+) T cells in the infected lung early
      (days 5-7) in the primary response. These results suggest that the frequency and
      number of specific CTL present in the lung early in infection may be
      underestimated by standard detection methods, and primary CD8(+) T cell expansion
      may occur in both secondary lymphoid organs and the infected lung.

PMID- 15843531
TI  - Reducing the stimulation of CD8+ T cells during infection with intracellular
      bacteria promotes differentiation primarily into a central (CD62LhighCD44high)
      subset.
AB  - During infection with lymphocytic choriomeningitis virus, CD8(+) T cells
      differentiate rapidly into effectors (CD62L(low)CD44(high)) that differentiate
      further into the central memory phenotype (CD62L(high)CD44(high)) gradually. To
      evaluate whether this CD8(+) T cell differentiation program operates in all
      infection models, we evaluated CD8(+) T cell differentiation during infection of
      mice with recombinant intracellular bacteria, Listeria monocytogenes (LM) and
      Mycobacterium bovis (BCG), expressing OVA. We report that CD8(+) T cells primed
      during infection with the attenuated pathogen BCG-OVA differentiated primarily
      into the central subset that correlated to reduced attrition of the primed cells
      subsequently. CD8(+) T cells induced by LM-OVA also differentiated into central
      phenotype cells first, but the cells rapidly converted into effectors in contrast
      to BCG-OVA. Memory CD8(+) T cells induced by both LM-OVA as well as BCG-OVA were
      functional in that they produced cytokines and proliferated extensively in
      response to antigenic stimulation after adoptive transfer. During LM-OVA
      infection, if CD8(+) T cells were guided to compete for access to APCs, then they
      received reduced stimulation that was associated with increased differentiation
      into the central subset and reduced attrition subsequently. Similar effect was
      observed when CD8(+) T cells encountered APCs selectively during the waning phase
      of LM-OVA infection. Taken together, our results indicate that the potency of the
      pathogen can influence the differentiation and fate of CD8(+) T cells enormously,
      and the extent of attrition of primed CD8(+) T cells correlates inversely to the
      early differentiation of CD8(+) T cells primarily into the central CD8(+) T cell
      subset.

PMID- 15843532
TI  - Accessory protein-like is essential for IL-18-mediated signaling.
AB  - IL-18 is an essential cytokine for both innate and adaptive immunity. Signaling
      by IL-18 requires IL-18Ralpha, which binds specifically to the ligand and
      contains sequence homology to IL-1R and TLRs. It is well established that IL-1R
      signaling requires an accessory cell surface protein, AcP. Other accessory
      proteins also exist with roles in regulating TLR signaling, but some have
      inhibitory functions. An AcP-like molecule (AcPL) has been identified with the
      ability to cooperate with IL-18Ralpha in vitro; however, the physiological
      function of AcPL remains unknown. In this study, we demonstrate that IL-18
      signals are abolished in AcPL-deficient mice and cells. Splenocytes from mutant
      mice fail to respond to IL-18-induced proliferation and IFN-gamma production. In
      particular, Th1 cells lacking AcPL fail to produce IFN-gamma in response to IL
      18. AcPL-deficient neutrophils also fail to respond to IL-18-induced activation
      and cytokine production. Furthermore, AcPL is required for NK-mediated
      cytotoxicity induced by in vivo IL-18 stimulation. However, AcPL is dispensable
      for the activation or inhibition of IL-1R and the various TLR signals that we
      have examined. These results suggest that AcPL is a critical and specific cell
      surface receptor that is required for IL-18 signaling.

PMID- 15843533
TI  - The influence of immune complex-bearing follicular dendritic cells on the IgM
      response, Ig class switching, and production of high affinity IgG.
AB  - It is believed that Ag in immune complexes (ICs) on follicular dendritic cells
      (FDCs) selects high affinity B cells and promotes affinity maturation. However,
      selection has been documented in the absence of readily detectable ICs on FDCs,
      suggesting that FDC-ICs may not be important. These results prompted experiments
      to test the hypothesis that IC-bearing murine FDCs can promote high affinity IgG
      responses by selecting B cells after stimulating naive IgM(+) cells to mature and
      class switch. Coculturing naive lambda(+) B cells, FDCs, (4-hydroxy-3
      nitrophenyl)acetyl-chicken gamma-globulin (CGG) + anti-CGG ICs, and CGG-primed T
      cells resulted in FDC-lymphocyte clusters and production of anti-4-hydroxy-5-iodo
      3-nitrophenyl acetyl. Class switching was indicated by a shift from IgM to IgG,
      and affinity maturation was indicated by a change from mostly low affinity IgM
      and IgG in the first week to virtually all high affinity IgG anti-4-hydroxy-5
      iodo-3-nitrophenyl acetyl in the second week. Class switching and affinity
      maturation were easily detectable in the presence of FDCs bearing appropriate
      ICs, but not in the absence of FDCs. Free Ag plus FDCs resulted in low affinity
      IgG, but affinity maturation was only apparent when FDCs bore ICs. Class
      switching is activation-induced cytidine deaminase (AID) dependent, and blocking
      FDC-CD21 ligand-B cell CD21 interactions inhibited FDC-IC-mediated enhancement of
      AID production and the IgG response. In short, these data support the concept
      that ICs on FDCs can promote AID production, class switching, and maturation of
      naive IgM(+) B cells, and further suggest that the IC-bearing FDCs help select
      high affinity B cells that produce high affinity IgG.

PMID- 15843534
TI  - Protective immunity against disparate tumors is mediated by a nonpolymorphic MHC
      class I molecule.
AB  - Current peptide-based immunotherapies for treatment of model cancers target tumor
      Ags bound by the classical MHC class I (class Ia) molecules. The extensive
      polymorphism of class Ia loci greatly limits the effectiveness of these
      approaches. We demonstrate in this study that the murine nonpolymorphic,
      nonclassical MHC class I (class Ib) molecule Q9 (Qa-2) promotes potent immune
      responses against multiple syngeneic tumors. We have previously shown that
      ectopic expression of Q9 on the surface of class Ia-negative B78H1 melanoma led
      to efficient CTL-mediated rejection of this tumor. In this study, we report that
      surface-expressed Q9 on 3LLA9F1 Lewis lung carcinoma and RMA T cell lymphoma also
      induces potent antitumor CTL responses. Importantly, CTL harvested from animals
      surviving the initial challenge with Q9-positive 3LLA9F1, RMA, or B78H1 tumors
      recognized and killed their cognate tumors as well as the other cancer lines.
      Furthermore, immunization with Q9-expressing 3LLA9F1 or RMA tumor cells
      established immunological memory that enhanced protection against subsequent
      challenge with a weakly immunogenic, Q9-bearing melanoma variant. Collectively,
      the generation of cross-reactive CTL capable of eliminating multiple disparate Q9
      expressing tumors suggests that this nonpolymorphic MHC class I molecule serves
      as a restriction element for a shared tumor Ag(s) common to lung carcinoma, T
      cell lymphoma, and melanoma.

PMID- 15843535
TI  - B cell receptor (BCR) cross-talk: IL-4 creates an alternate pathway for BCR
      induced ERK activation that is phosphatidylinositol 3-kinase independent.
AB  - IL-4 has pleiotropic effects on B cells. These effects include alteration of
      subsequent BCR-triggered responses. To identify a molecular basis for this
      receptor cross-talk, we examined ERK activation and NF-kappaB induction. We found
      that treatment with IL-4, but not other cytokines, affected subsequent BCR
      signaling by creating a new pathway in which the need for PI3K in ERK activation
      was eliminated. In contrast, the need for PI3K in NF-kappaB induction was not
      altered. The new pathway for ERK required time to develop, depended on STAT6, and
      was blocked by inhibition of macromolecular synthesis. As in the classical
      pathway, BCR-induced ERK activation in the new, PI3K-independent pathway required
      MEK and was reflected in c-Raf. Thus, IL-4 promotes an alternate pathway through
      which BCR is coupled to Raf/MEK/ERK that may function to heighten the
      responsiveness of B cells during times of immunological stress.

PMID- 15843536
TI  - Priming in the presence of IL-10 results in direct enhancement of CD8+ T cell
      primary responses and inhibition of secondary responses.
AB  - Although IL-10 acts as an inhibitory cytokine for APC and CD4(+) T cell function,
      its effects on CD8(+) T cells are unclear. Additionally, little is known about
      whether initial priming in the presence of IL-10 can have long-lasting effects
      and influence subsequent CD8(+) T cell responses that occur in the absence of the
      cytokine. In the present study, we clarified the role of IL-10 during primary
      responses and examined whether exposure to IL-10 during initial priming of CD8(+)
      T cells impacted secondary responses. To determine the effect of IL-10 on Ag
      specific T cell responses, peptide-pulsed IL-10R2(-/-) splenic dendritic cells
      were used to prime T cells from OT-I CD8(+) TCR transgenic mice. During the
      primary response, the presence of IL-10 resulted in enhancement of CD8(+) T cell
      numbers without detectable alterations in the kinetics or percentage of cells
      that underwent proliferation. A modest increase in survival, not attributable to
      Bcl-2 or Bcl-x(L), was also observed with IL-10 treatment. Other parameters of
      CD8(+) T cell function, including IL-2, IFN-gamma, TNF-alpha, and granzyme
      production, were unaltered. In contrast, initial exposure to IL-10 during the
      primary response resulted in decreased OT-I expansion during secondary
      stimulation. This was accompanied by lowered IL-2 levels and reduced percentages
      of proliferating BrdU(+) cells and OT-I cells that were CD25(high). IFN-gamma,
      TNF-alpha, and granzyme production were unaltered. These data suggest that
      initial exposure of CD8(+) T cells to IL-10 may be temporarily stimulatory;
      however, programming of the cells may be altered, resulting in diminished overall
      responses.

PMID- 15843537
TI  - Saturated and polyunsaturated fatty acids reciprocally modulate dendritic cell
      functions mediated through TLR4.
AB  - TLRs provide critical signals to induce innate immune responses in APCs such as
      dendritic cells (DCs) that in turn link to adaptive immune responses. Results
      from our previous studies demonstrated that saturated fatty acids activate TLRs,
      whereas n-3 polyunsaturated fatty acids inhibit agonist-induced TLR activation.
      These results raise a significant question as to whether fatty acids
      differentially modulate immune responses mediated through TLR activation. The
      results presented in this study demonstrate that the saturated fatty acid, lauric
      acid, up-regulates the expression of costimulatory molecules (CD40, CD80, and
      CD86), MHC class II, and cytokines (IL-12p70 and IL-6) in bone marrow-derived
      DCs. The dominant negative mutant of TLR4 or its downstream signaling components
      inhibits lauric acid-induced expression of a CD86 promoter-reporter gene. In
      contrast, an n-3 polyunsaturated fatty acid, docosahexaenoic acid, inhibits TLR4
      agonist (LPS)-induced up-regulation of the costimulatory molecules, MHC class II,
      and cytokine production. Similarly, DCs treated with lauric acid show increased T
      cell activation capacity, whereas docosahexaenoic acid inhibits T cell activation
      induced by LPS-treated DCs. Together, our results demonstrate that the reciprocal
      modulation of both innate and adaptive immune responses by saturated fatty acid
      and n-3 polyunsaturated fatty acid is mediated at least in part through TLRs.
      These results imply that TLRs are involved in sterile inflammation and immune
      responses induced by nonmicrobial endogenous molecules. These results shed new
      light in understanding how types of dietary fatty acids differentially modulate
      immune responses that could alter the risk of many chronic diseases.

PMID- 15843538
TI  - A large number of T lymphocytes recognize Moloney-murine leukemia virus-induced
      antigens, but a few mediate long-lasting tumor immunosurveillance.
AB  - The CD8(+) T cell response to Moloney-murine leukemia virus (M-MuLV)-induced Ags
      is almost entirely dominated by the exclusive expansion of lymphocytes that use
      preferential TCRVbeta chain rearrangements. In mice lacking T cells expressing
      these TCRVbeta, we demonstrate that alternative TCRVbeta can substitute for the
      lack of the dominant TCRVbeta in the H-2-restricted M-MuLV Ag recognition. We
      show that, at least for the H-2(b)-restricted response, the shift of TCR usage is
      not related to a variation of the immunodominant M-MuLV epitope recognition.
      After virus immunization, all the potentially M-MuLV-reactive lymphocytes are
      primed, but only the deletion of dominant Vbeta rescues the alternative Vbeta
      response. The mechanism of clonal T cell "immunodomination" that guides the
      preferential Vbeta expansion is likely the result of a proliferative advantage of
      T cells expressing dominant Vbeta, due to differences in TCR affinity and/or
      cosignal requirements. In this regard, a CD8 involvement is strictly required for
      the virus-specific cytotoxic activity of CTL expressing alternative, but not
      dominant, Vbeta gene rearrangements. The ability of T cells expressing
      alternative TCRVbeta rearrangements to mediate tumor protection was evaluated by
      a challenge with M-MuLV tumor cells. Although T cells expressing alternative
      Vbeta chains were activated and expanded, they were not able to control tumor
      growth in a long-lasting manner due to their incapacity of conversion and
      accumulation in the T central memory pool.

PMID- 15843539
TI  - Corticotropin-releasing hormone contributes to the peripheral inflammatory
      response in experimental autoimmune encephalomyelitis.
AB  - Peripheral corticotropin-releasing hormone (CRH) is thought to have
      proinflammatory effects. We used the model of experimental autoimmune
      encephalomyelitis (EAE) to study the role of CRH in an immune-mediated disease.
      We showed that CRH-deficient mice are resistant to EAE, with a decrease in
      clinical score as well as decreased cellular infiltration in the CNS.
      Furthermore, Ag-specific responses of primed T cells as well as anti-CD3/anti
      CD28 TCR costimulation were decreased in crh(-/-) mice with decreased production
      of Th1 cytokines and increased production of Th2 cytokines. Wild-type mice
      treated in vivo with a CRH antagonist showed a decrease in IFN-gamma production
      by primed T cells in vitro. This effect of CRH is independent of its ability to
      increase corticosterone production, because adrenalectomized wild-type mice had
      similar disease course and severity as control mice. We found that IkappaBalpha
      phosphorylation induced by TCR cross-linking was decreased in crh(-/-) T cells.
      We conclude that peripheral CRH exerts a proinflammatory effect in EAE with a
      selective increase in Th1-type responses. These findings have implications for
      the treatment of Th1-mediated diseases such as multiple sclerosis.

PMID- 15843540
TI  - Phenotypic characterization of CD3-7+ cells in developing human intestine and an
      analysis of their ability to differentiate into T cells.
AB  - We have identified a large population of CD3(-)7(+) cells in human fetal gut.
      Three- and four-color flow cytometry revealed a distinct surface Ag profile on
      this population; the majority were negative for CD4 and CD8, whereas most of the
      remainder expressed the CD8alphaalpha homodimer. In contrast about half of CD3(+)
      cells expressed CD4 and half expressed CD8alpha. A large proportion of CD3(-)7(+)
      cells expressed CD56, CD94, and CD161, and whereas CD3(+) T cells also expressed
      CD161, they only rarely expressed CD56 or CD94. Further studies were conducted to
      determine whether the CD3(-)7(+) cells have the potential to differentiate into
      CD3(+) cells. About half of CD3(-)7(+) cells contain intracellular CD3epsilon.
      Rearranged TCR gamma-chains were detected in highly purified CD3(-)7(+) cells as
      an early molecular sign of T cell commitment, and the pattern of rearrangement
      with V regions spliced to the most 5' Jgamma segment is reminiscent of early
      thymocyte differentiation. In reaggregate thymic organ cultures, CD3(-)7(+) cells
      also gave rise to CD3(+) T cells. Thus, we demonstrate that the CD3(-)7(+) cells
      present in the human fetal gut display a distinct phenotype and are able to
      develop into CD3(+) T cells.

PMID- 15843541
TI  - Signal-specific activation and regulation of human neutrophil Fc gamma receptors.
AB  - FcgammaRs with the ITIM domain have been shown to regulate the inflammatory
      signal delivered by the ITAM-containing FcgammaRs. In this study, we demonstrate
      that the function of human neutrophil FcgammaR type IIA (CD32A) is regulated in a
      distinct manner by different cell activation signals at the ligand-binding stage.
      Activation of neutrophils with fMLP up-regulated the ligand-binding function of
      CD32A, whereas PMA-mediated activation completely abolished ligand binding
      without altering CD32A expression. Furthermore, PMA treatment also abolished
      CD16B-dependent ligand binding irrespective of the level of expression. The
      effect of PMA was cell type specific, because the ligand-binding function of
      CD32A expressed on cultured cells such as K562 and CHO-CD32A transfectants was
      not affected by PMA. Interestingly, phorbol 12,13-dibutyrate, another phorbol
      ester, and IL-8 up-regulated CD32A-dependent ligand-binding function. These
      results demonstrate that regulation of CD32A-dependent ligand binding in human
      neutrophils is not only cell type specific but also activation signal specific.
      Moreover, these results suggest the possibility that signals delivered to
      neutrophils by various inflammatory stimuli can exert opposing effects on the
      function of human FcgammaRs, representing a novel inside-out regulatory mechanism
      of FcgammaR ligand binding.

PMID- 15843542
TI  - Modulation of memory CD4 T cell function and survival potential by altering the
      strength of the recall stimulus.
AB  - Optimization of long term immunity depends on the functional persistence of
      memory T cells; however, there are no defined strategies for promoting memory T
      cell function and survival. In this study, we hypothesized that varying the
      strength of the recall stimulus could modulate the function and survival
      potential of memory CD4 T cells. We tested the ability of peptide variants of
      influenza hemagglutinin (HA) exhibiting strong and weak avidity for an HA
      specific TCR, to modulate HA-specific memory CD4 T cells in vitro and in vivo. In
      vitro stimulation with a weak avidity peptide (L115) uncoupled memory CD4 T
      proliferation from effector cytokine production with low apoptosis, whereas
      stimulation with a strong avidity peptide (Y117) fully recalled memory T cell
      functions but triggered increased apoptosis. To determine how differential recall
      would affect memory T cells in vivo, we boosted BALB/c hosts of transferred, CFSE
      labeled HA-specific memory CD4 T cells with native HA, Y117, and L115 variant
      peptides and found differences in early Ag-driven memory T cell proliferation and
      IL-7R expression, with subsequent changes in memory T cell yield. High avidity
      boosting resulted in rapid proliferation, extensive IL-7R down-regulation, and
      the lowest yield of HA-specific memory cells, whereas low avidity boosting
      triggered low in vivo proliferation, maintenance of IL-7R expression, and the
      highest memory T cell yield. Our results indicate that memory CD4 T cell function
      and survival can be modulated at the recall level, and can be optimized by low
      level stimulation that minimizes apoptosis and enhances responses to survival
      factors.

PMID- 15843543
TI  - Granzyme B binds to target cells mostly by charge and must be added at the same
      time as perforin to trigger apoptosis.
AB  - Perforin (PFN) delivery of granzymes (Gzm) into the target cell at the
      immunological synapse is the major pathway for inducing apoptosis of virus
      infected cells and tumors. A validated model for how PFN delivers Gzm into the
      cytosol is still lacking. PFN was originally thought to work by forming pores in
      the target cell plasma membrane that allow Gzm entry. This model was questioned
      when it was shown that GzmB is endocytosed without PFN. Moreover, apoptosis could
      be triggered by adding PFN to washed cells that have previously endocytosed GzmB.
      In this study, we show that GzmB binds to the plasma membrane mostly via
      nonspecific charge interactions. Washing in saline does not remove bound Gzm.
      However, if externally bound GzmB is completely removed, subsequent addition of
      PFN does not release previously endocytosed GzmB and does not trigger apoptosis.
      Therefore, PFN must be coendocytosed with GzmB to deliver it into the cytosol.

PMID- 15843544
TI  - Role of type I IFNs in pulmonary complications of Pneumocystis murina infection.
AB  - Despite the advent of highly active antiretroviral therapy, pulmonary
      complications in AIDS are a common clinical problem. Pneumocystis jiroveci
      infection causes a life-threatening pneumonia, especially in individuals with CD4
      T cell deficiencies as occurs in AIDS. Although Pneumocystis sp. is an
      extracellular fungal pathogen, CD8 T cells are the predominant lymphocyte
      recruited to the lung in CD4-deficient humans and mice during Pneumocystis
      pneumonia, and we have found that these CD8 T cells are responsible for
      subsequent lung damage in CD4 T cell-depleted mice. Comparing CD4 T cell-depleted
      IFN-alpha receptor knockout (KO) mice to wild-type mice, we found that this CD8 T
      cell recruitment and lung damage is type I IFN (IFN-alphabeta) dependent.
      However, in both CD4 competent, wild-type and IFN-alpha receptor (IFNAR) KO mice,
      Pneumocystis infection leads to an eosinophilic granulocyte influx with bronchial
      epithelial changes as seen in asthma. This response is delayed in IFNAR KO mice,
      as is pathogen clearance. Although the inflammation is transient in wild-type
      animals and resolves upon Pneumocystis clearance, it is more severe and persists
      through day 35 postinfection in IFNAR KO mice, leading to fibrosis. In addition,
      IFNAR KO, but not wild-type, mice mount a Pneumocystis-specific IgE response, an
      indicator of allergic sensitization. Thus, in the absence of IFNAR signaling and
      CD4 T cells, Pneumocystis-mediated lung damage does not occur, whereas in CD4
      competent animals, the absence of IFNAR signaling results in an exacerbated Th2
      response, asthma-like symptoms, and fibrosis. Therefore, both CD4 T cell- and
      type I IFN-mediated mechanisms can determine pulmonary complications from
      Pneumocystis infection.

PMID- 15843545
TI  - Immature neutrophils mediate tumor cell killing via IgA but not IgG Fc receptors.
AB  - Antitumor Abs are promising therapeutics for cancer. Currently, most Ab-based
      therapies focus on IgG Ab, which interact with IgG FcR (FcgammaR) on effector
      cells. In this study, we examined human and mouse neutrophil-mediated tumor cell
      lysis via targeting the IgA FcR, FcalphaRI (CD89), in more detail. FcalphaRI was
      the most effective FcR in triggering tumor cell killing, and initiated enhanced
      migration of neutrophils into tumor colonies. Importantly, immature neutrophils
      that are mobilized from the bone marrow upon G-CSF treatment efficiently
      triggered tumor cell lysis via FcalphaRI, but proved incapable of initiating
      tumor cell killing via FcgammaR. This may provide a rationale for the
      disappointing results observed in some earlier clinical trials in which patients
      were treated with G-CSF and antitumor Ab-targeting FcgammaR.

PMID- 15843546
TI  - Targeted delivery of the ErbB2/HER2 tumor antigen to professional APCs results in
      effective antitumor immunity.
AB  - Activation of T cells by professional APCs that present peptide epitopes of tumor
      associated Ags is critical for the induction of cell-mediated immunity against
      tumors. To facilitate targeted delivery of the ErbB2 (HER2, neu) tumor Ag to APCs
      in vivo, we have generated chimeric proteins that contain the extracellular
      domain of CTLA-4 for binding to B7 molecules on the APC surface, which is
      genetically fused to a human ErbB2 fragment as an antigenic determinant.
      Bacterially expressed CTLA-4-ErbB2 fusion protein and a similar molecule
      harboring in addition the translocation domain of Pseudomonas exotoxin A as an
      endosome escape function displayed specific binding to B7-expressing cells,
      followed by protein internalization and intracellular degradation. Vaccination of
      BALB/c mice with the fusion proteins resulted in the induction of ErbB2-specific
      CD8(+) T cells and CTL-dependent protection from subsequent challenge with ErbB2
      expressing but not ErbB2-negative murine renal carcinoma cells. In a therapeutic
      setting, injection of CTLA-4-ErbB2 protein vaccines caused rejection of
      established ErbB2-expressing tumors. Thereby, immunological memory was induced,
      leading to long-term systemic immunity and protection against rechallenge several
      months later. Our results demonstrate that these chimeric protein vaccines are
      effective tools for the induction of ErbB2-specific, T cell-mediated immunity.

PMID- 15843547
TI  - Loss of new chemokine CXCL14 in tumor tissue is associated with low infiltration
      by dendritic cells (DC), while restoration of human CXCL14 expression in tumor
      cells causes attraction of DC both in vitro and in vivo.
AB  - Breast and kidney-expressed chemokine (BRAK) CXCL14 is a new CXC chemokine with
      unknown function and receptor selectivity. The majority of head and neck squamous
      cell carcinoma (HNSCC) and some cervical squamous cell carcinoma do not express
      CXCL14 mRNA, as opposed to constitutive expression by normal oral squamous
      epithelium. In this study, we demonstrate that the loss of CXCL14 in HNSCC cells
      and at HNSCC primary tumor sites was correlated with low or no attraction of
      dendritic cell (DC) in vitro, and decreased infiltration of HNSCC mass by DC at
      the tumor site in vivo. Next, we found that recombinant human CXCL14 and CXCL14
      positive HNSCC cell lines induced DC attraction in vitro, whereas CXCL14-negative
      HNSCC cells did not chemoattract DC. Transduction of CXCL14-negative HNSCC cell
      lines with the human CXCL14 gene resulted in stimulation of DC attraction in
      vitro and increased tumor infiltration by DC in vivo in chimeric animal models.
      Furthermore, evaluating the biologic effect of CXCL14 on DC, we demonstrated that
      the addition of recombinant human CXCL14 to DC cultures resulted in up-regulation
      of the expression of DC maturation markers, as well as enhanced proliferation of
      allogeneic T cells in MLR. Activation of DC with recombinant human CXCL14 was
      accompanied by up-regulation of NF-kappaB activity. These data suggest that
      CXCL14 is a potent chemoattractant and activator of DC and might be involved in
      DC homing in vivo.

PMID- 15843548
TI  - Breakdown of mucosal immunity in the gut and resultant systemic sensitization by
      oral antigens in a murine model for systemic lupus erythematosus.
AB  - Secreted IgA plays a pivotal role in the mucosal immunity to maintain the front
      line of body defense. We found that the level of fecal IgA was dramatically
      decreased in aged (NZB x NZW)F(1) (BWF(1)) mice developing lupus nephritis,
      whereas levels in similarly aged New Zealand Black (NZB) and New Zealand White
      (NZW) mice remained unchanged compared with young mice. The number of cells
      obtained from Peyer's patches was markedly decreased in aged BWF(1) mice. Aged
      BWF(1) mice showed increased susceptibility to pathogenic bacterial infection.
      Furthermore, oral administration of OVA failed to inhibit secondary IgG response
      induced by systemic immunization, suggesting defective oral tolerance in aged
      BWF(1) mice. A significant amount of orally administered OVA was incorporated
      directly into the intestinal lamina propria in aged BWF(1) mice whereas it was
      mainly localized in subepithelial domes and interfollicular region in Peyer's
      patches in young mice. T cells obtained from renal and pulmonary lymph nodes of
      aged BWF(1) mice that had been orally administered with OVA showed an Ag-specific
      T cell proliferation, whereas those from young BWF(1), aged NZB, and aged NZW
      mice did not. Interestingly, aerosol exposure to OVA of aged BWF(1) mice, which
      had been orally administered with the same Ag, provoked an eosinophil
      infiltration in the lung. These results demonstrate that mucosal immunity in the
      gut is impaired and oral Ags induce systemic sensitization instead of oral
      tolerance in the development of murine lupus.

PMID- 15843549
TI  - Blocking IL-15 prevents the induction of allergen-specific T cells and allergic
      inflammation in vivo.
AB  - IL-15 has been shown to accelerate and boost allergic sensitization in mice.
      Using a murine model of allergic sensitization to OVA, we present evidence that
      blocking endogenous IL-15 during the sensitization phase using a soluble IL
      15Ralpha (sIL-15Ralpha) suppresses the induction of Ag-specific, Th2
      differentiated T cells. This significantly reduces the production of OVA-specific
      IgE and IgG and prevents the induction of a pulmonary inflammation. Release of
      proinflammatory TNF-alpha, IL-1beta, IL-6, and IL-12 as well as that of Th2
      cytokines IL-4, IL-5, and IL-13 into the bronchi are significantly reduced,
      resulting in suppressed recruitment of eosinophils and lymphocytes after allergen
      challenge. It is of clinical relevance that the airway hyper-responsiveness, a
      major symptom of human asthma bronchiale, is significantly reduced by sIL
      15Ralpha treatment. Ex vivo analysis of the draining lymph nodes revealed reduced
      numbers of CD8, but not CD4, memory cells and the inability of T cells of sIL
      15Ralpha-treated mice to proliferate and to produce Th2 cytokines after in vitro
      OVA restimulation. This phenomenon is not mediated by enhanced numbers of
      CD4(+)/CD25(+) T cells. These results show that IL-15 is important for the
      induction of allergen-specific, Th2-differentiated T cells and induction of
      allergic inflammation in vivo.

PMID- 15843550
TI  - Insulin-like growth factor-1 controls type 2 T cell-independent B cell response.
AB  - The IGF-1 receptor (IGF-1R) is expressed on T and B lymphocytes, and the
      expression of the insulin- and IGF-1-signaling machinery undergoes defined
      changes throughout lineage differentiation, offering a putative role for IGF-1 in
      the regulation of immune responses. To study the role of the IGF-1R in lymphocyte
      differentiation and function in vivo, we have reconstituted immunodeficient RAG2
      deficient mice with IGF-1R(-/-) fetal liver cells. Despite the absence of IGF
      1Rs, the development and ex vivo activation of B and T lymphocytes were unaltered
      in these chimeric mice. By contrast, the humoral immune response to the T cell
      independent type 2 Ag 4-hydroxy-3-nitrophenyl acetyl-Ficoll was significantly
      reduced in mice reconstituted with IGF-1R-deficient fetal liver cells, whereas
      responses to the T cell-dependent Ag 4-hydroxy-3-nitrophenyl acetyl-chicken
      globulin were normal. Moreover, in an in vitro model of T cell-independent type 2
      responses, IGF-1 promoted Ig production potently upon polyvalent membrane-IgD
      cross-linking. These data indicate that functional IGF-1R signaling is required
      for T cell-independent B cell responses in vivo, defining a novel regulatory
      mechanism for the immune response against bacterial polysaccharides.

PMID- 15843551
TI  - Lymphotoxin-beta receptor-dependent genes in lymph node and follicular dendritic
      cell transcriptomes.
AB  - Affinity maturation and Ab class switches occur in lymphoid germinal centers
      (GCs), in which differentiation and maintenance depend on lymphotoxin (LT)
      signaling and include differentiation of follicular dendritic cells (FDCs). The
      events leading to FDC and GC maturation are poorly defined. Using several
      approaches of functional genomics, we enumerated transcripts affected in mice by
      suppressing LT beta receptor (LTbetaR) signaling and/or overrepresented in FDC
      enriched GC isolates. Protein expression analysis of 3 of 12 genes both enriched
      in FDCs and down-regulated by LTbetaR signaling suppression validated them as FDC
      markers. Functional analysis of one of these three, clusterin, suggests a role as
      an FDC-derived trophic factor for GC B cells. Hence, the set of genes presented
      in this study includes markers emanating from LTbetaR signaling and transcripts
      relevant to GC and FDC function.

PMID- 15843552
TI  - BAFF augments certain Th1-associated inflammatory responses.
AB  - B cell-activating factor belonging to the TNF family (BAFF; BLyS) is a critical
      regulator of B cell maturation and survival, and its overexpression in BAFF
      transgenic (Tg) mice results in the development of autoimmune disorders. BAFF
      also affects T cell function through binding to one of the BAFF receptors, BAFF
      R. Using BAFF Tg mice, we examined a typical Th1-mediated response, the cutaneous
      delayed-type hypersensitivity reaction, and found a much greater degree of paw
      swelling and inflammation than in control mice. Importantly, delayed-type
      hypersensitivity scores correlated directly with BAFF levels in serum.
      Conversely, in a Th2-mediated model of allergic airway inflammation, BAFF Tg mice
      were largely protected and showed markedly reduced Ag-specific T cell
      proliferation and eosinophil infiltration associated with the airways. Thus,
      local and/or systemically distributed BAFF affects Th1 and Th2 responses and
      impacts on the course of some T cell-mediated inflammatory reactions. Our results
      are consistent with the idea that BAFF augments T cell as well as B cell
      responses, particularly Th1-type responses. Results in BAFF Tg mice may reflect
      the situation in certain autoimmune patients or virally infected individuals,
      because BAFF levels in blood are comparable.

PMID- 15843553
TI  - Dendritic cells endocytose Bacillus anthracis spores: implications for anthrax
      pathogenesis.
AB  - Phagocytosis of inhaled Bacillus anthracis spores and subsequent trafficking to
      lymph nodes are decisive events in the progression of inhalational anthrax
      because they initiate germination and dissemination of spores. Found in high
      frequency throughout the respiratory track, dendritic cells (DCs) routinely take
      up foreign particles and migrate to lymph nodes. However, the participation of
      DCs in phagocytosis and dissemination of spores has not been investigated
      previously. We found that human DCs readily engulfed fully pathogenic Ames and
      attenuated B. anthracis spores predominately by coiling phagocytosis. Spores
      provoked a loss of tissue-retaining chemokine receptors (CCR2, CCR5) with a
      concurrent increase in lymph node homing receptors (CCR7, CD11c) on the membrane
      of DCs. After spore infection, immature DCs displayed a mature phenotype
      (CD83(bright), HLA-DR(bright), CD80(bright), CD86(bright), CD40(bright)) and
      enhanced costimulatory activity. Surprisingly, spores activated the MAPK cascade
      (ERK, p38) within 30 min and stimulated expression of several inflammatory
      response genes by 2 h. MAPK signaling was extinguished by 6 h infection, and
      there was a dramatic reduction of secreted TNF-alpha, IL-6, and IL-8 in the
      absence of DC death. This corresponded temporally with enzymatic cleavage of
      proximal MAPK signaling proteins (MEK-1, MEK-3, and MAP kinase kinase-4) and may
      indicate activity of anthrax lethal toxin. Taken together, these results suggest
      that B. anthracis may exploit DCs to facilitate infection.

PMID- 15843554
TI  - Expression of RAGs in peripheral B cells outside germinal centers is associated
      with the expression of CD5.
AB  - Previous studies have indicated that mature B cells reactivate secondary V(D)J
      recombination inside and outside the germinal center (GC) of peripheral lymphoid
      organs. The nature of the B cells undergoing Ig rearrangement before they enter
      GC is unknown. In this study, we present evidence that activated mature CD5
      positive human tonsil B cells coexpress both RAG1 and RAG2 mRNA and protein, and
      display DNA cleavage resulting from their recombinase activity. Furthermore, in
      vitro activation of CD5-negative naive mature B cells by IgR and CD40 cross
      linking induces expression of CD5 on a subset of cells, and leads to the up
      regulation of RAG1 and RAG2 only in cells turned positive for CD5. Thus, RAG gene
      expression is closely related to CD5 expression outside GCs. These data suggest
      that CD5 is associated with receptor revision in activated mature B cells and
      likely to promote expression of suitable IgR capable of initiating the GC
      reaction.

PMID- 15843555
TI  - Intracellular trafficking of CD23: differential regulation in humans and mice by
      both extracellular and intracellular exons.
AB  - In mouse models of food allergy, we recently characterized a new CD23b-derived
      splice form lacking extracellular exon 5, bDelta5, which undergoes constitutive
      internalization and mediates the transepithelial transport of free IgE, whereas
      classical CD23b is more efficient in transporting IgE/allergen complexes. These
      data suggested that regulation of endocytosis plays a central role in CD23
      functions and drove us to systematically compare the intracellular trafficking
      properties of human and murine CD23 splice forms. We found that CD23 species show
      similar endocytic behaviors in both species; CD23a undergoes constitutive
      clathrin-dependent internalization, whereas CD23b is stable at the plasma
      membrane. However, the mechanisms controlling these similar behaviors appeared to
      be different. In mice, a positive internalization signal was localized in the
      cytoplasmic region shared by all CD23 splice forms. This positive signal was
      negatively regulated by the intracellular CD23b-specific exon. In addition, the
      fact that alternative splice forms lacking exons of the extracellular region (5,
      6, 7, and/or 8) were all constitutively internalized suggested that endocytosis
      of murine CD23 is regulated by a process similar to the outside-in signaling of
      integrins. In humans, the internalization signal was mapped in the CD23a-specific
      intracellular exon. Interestingly, this signal also behaved as a basolateral
      targeting signal in polarized Madin-Darby canine kidney cells. The latter result
      and the fact that human intestinal cell lines were found to coexpress both CD23a
      and CD23b provide a molecular explanation for the initial observations that CD23
      was found at the basolateral membrane of intestinal epithelial cells from
      allergic patients.

PMID- 15843556
TI  - Human NK cells lyse organ-specific endothelial cells: analysis of adhesion and
      cytotoxic mechanisms.
AB  - Human organ-specific microvascular endothelial cells (ECs) were established and
      used in the present study to investigate their susceptibility to natural killer
      cell line (NKL)-induced lysis. Our data indicate that although IL-2-stimulated
      NKL (NKL2) cells adhered to the human peripheral (HPLNEC.B3), mesenteric lymph
      node (HMLNEC), brain (HBrMEC), and lung (HLMEC) and skin (HSkMEC.2) ECs, they
      significantly killed these cells quite differently. A more pronounced lysis of
      OSECs was also observed when IL-2-stimulated, purified peripheral blood NK cells
      were used as effector cells. In line with the correlation observed between
      adhesion pattern and the susceptibility to NKL2-mediated killing, we demonstrated
      using different chelators that the necessary adhesion step was governed by an
      Mg(2+)-dependent, but Ca(2+)-independent, mechanism as opposed to the subsequent
      Ca(2+)-dependent killing. To identify the cytotoxic pathway used by NKL2 cells,
      the involvement of the classical and alternate pathways was examined. Blocking of
      the Ca(2+)-dependent cytotoxicity pathway by EGTA/MgCl(2) significantly inhibited
      endothelial target cell killing, suggesting a predominant role for the
      perforin/granzyme pathway. Furthermore, using confocal microscopy, we
      demonstrated that the interaction between NKL2 effectors and ECs induced
      cytochrome c release and Bid translocation in target cells, indicating an
      involvement of the mitochondrial pathway in NKL2-induced EC death. In addition,
      although all tested cells were sensitive to the cytotoxic action of TNF, no
      susceptibility to TRAIL or anti-Fas mAb was observed. The present studies
      emphasize that human NK cell cytotoxicity toward ECs may be a potential target to
      block vascular injury.

PMID- 15843557
TI  - A pivotal role for the multifunctional calcium/calmodulin-dependent protein
      kinase II in T cells: from activation to unresponsiveness.
AB  - Stimulation of the TCR leads to an oscillatory release of free calcium that
      activates members of the calcium/calmodulin-dependent protein kinase II (CaMKII)
      family. The CaMKII molecules have profound and lasting effects on cellular
      signaling in several cell types, yet the role of CaMKII in T cells is still
      poorly characterized. In this report we describe a splice variant of CaMKIIbeta,
      CaMKIIbeta'e, in mouse T cells. We have determined its function, along with that
      of CaMKIIgamma, by introducing the active and kinase-dead mutants into activated
      P14 TCR transgenic T cells using retroviral transduction. Active CaMKII enhanced
      the proliferation and cytotoxic activity of T cells while reducing their IL-2
      production. Furthermore, it induced a profound state of unresponsiveness that
      could be overcome only by prolonged culture in IL-2. These results indicate that
      members of the CaMKII family play an important role in regulation of CD8 T cell
      proliferation, cytotoxic effector function, and the response to restimulation.

PMID- 15843558
TI  - Antagonism of antiviral and allogeneic activity of a human public CTL clonotype
      by a single altered peptide ligand: implications for allograft rejection.
AB  - Alloreactive T lymphocytes are central mediators of graft-versus-host disease and
      allograft rejection. A public CTL clonotype with specificity for the alloantigens
      HLA-B*4402 and B*4405 is often expanded to large numbers in healthy HLA-B*0801(+)
      individuals, driven by cross-reactive stimulation with the common, persistent
      herpesvirus EBV. Since such alloreactive memory CTL expansions have the potential
      to influence transplantation outcome, altered peptide ligands (APLs) of the
      target HLA-B*0801-binding EBV peptide, FLRGRAYGL, were screened as specific
      antagonists for this immunodominant clonotype. One APL, FLRGRFYGL, exerted
      powerful antagonism of a prototypic T cell clone expressing this immunodominant
      TCR when costimulated with target cells presenting HLA-B*0801(FLRGRAYGL).
      Significantly, this APL also reduced the lysis of allogeneic target cells
      expressing HLA-B*4402 by up to 99%. The affinities of the agonist and antagonist
      complexes for the public TCR, measured using solution and solid-phase assays,
      were 8 and 138 muM, respectively. Surprisingly, the half-life of the agonist and
      antagonist complexes was similar, yet the association rate for the antagonist
      complex was significantly slower. These observations were further supported by
      structural studies that suggested a large conformational hurdle was required to
      ligate the immunodominant TCR to the HLA-B*0801 antagonist complex. By defining
      an antagonist APL against an immunodominant alloreactive TCR, these findings
      raise the prospect of exploiting such peptides to inhibit clinical
      alloreactivity, particularly against clonal T cell expansions that react with
      alloantigens.

PMID- 15843559
TI  - Membrane IgE binds and activates Fc epsilon RI in an antigen-independent manner.
AB  - Interaction of secretory IgE with FcepsilonRI is the prerequisite for allergen
      driven cellular responses, fundamental events in immediate and chronic allergic
      manifestations. Previous studies reported the binding of soluble FcepsilonRIalpha
      to membrane IgE exposed on B cells. In this study, the functional interaction
      between human membrane IgE and human FcepsilonRI is presented. Four different IgE
      versions were expressed in mouse B cell lines, namely: a truncation at the
      Cepsilon2-Cepsilon3 junction of membrane IgE isoform long, membrane IgE isoform
      long (without Igalpha/Igbeta BCR accessory proteins), and both epsilonBCRs
      (containing membrane IgE isoforms short and long). All membrane IgE versions
      activated a rat basophilic leukemia cell line transfected with human FcepsilonRI,
      as detected by measuring the release of both preformed and newly synthesized
      mediators. The interaction led also to Ca(2+) responses in the basophil cell
      line, while membrane IgE-FcepsilonRI complexes were detected by
      immunoprecipitation. FcepsilonRI activation by membrane IgE occurs in an Ag
      independent manner. Noteworthily, human peripheral blood basophils and monocytes
      also were activated upon contact with cells bearing membrane IgE. In humans, the
      presence of FcepsilonRI in several cellular entities suggests a possible membrane
      IgE-FcepsilonRI-driven cell-cell dialogue, with likely implications for IgE
      homeostasis in physiology and pathology.

PMID- 15843560
TI  - Negative regulation of lymphocyte activation by the adaptor protein LAX.
AB  - The membrane-associated adaptor protein LAX is a linker for activation of T cells
      (LAT)-like molecule that is expressed in lymphoid tissues. Upon stimulation of T
      or B cells, it is phosphorylated and interacts with Grb2 and the p85 subunit of
      PI3K. LAX, however, is not capable of replacing LAT in the TCR signaling pathway.
      In this study we report that upon T or B cell activation, the LAX protein was up
      regulated dramatically. Although disruption of the LAX gene by homologous
      recombination had no major impact on lymphocyte development, it caused a
      significant reduction in CD23 expression on mature B cells. Interestingly, naive
      LAX(-/-) mice had spontaneous germinal center formation. Compared with normal T
      and B cells, LAX(-/-) T and B cells were hyperresponsive and had enhanced calcium
      flux, protein tyrosine phosphorylation, MAPK and Akt activation, and cell
      survival upon engagement of the T or B AgRs. Our data demonstrate that LAX
      functions as a negative regulator in lymphocyte signaling.

PMID- 15843561
TI  - Differential regulation of CCL22 gene expression in murine dendritic cells and B
      cells.
AB  - The activated T cell-attracting CC chemokine CCL22 is expressed by stimulated B
      cells and mature dendritic cells (DC). We have cloned and sequenced the complete
      mouse gene, including 4 kb of the 5'-flanking promoter region, and detected two
      distinct sites for initiation of transcription by 5'-RACE. Reporter gene assays
      indicate that the promoter reflects the specificity of the endogenous gene.
      Within the proximal promoter region, we identified potential binding sites for NF
      kappaB, Ikaros, and a putative GC box. All three regions bind proteins. The NF
      kappaB site was shown to specifically bind NF-kappaB subunits p50 and p65 from
      nuclear extracts of LPS-stimulated B cells, B cell line A20/2J, TNF-alpha
      stimulated bone marrow-derived DC, and DC line XS106. Furthermore, promoter
      activity was affected by targeted mutagenesis of the NF-kappaB site and
      transactivation with p50 and p65. The region harboring the putative Ikaros site
      contributes to promoter activity, but the binding protein does not belong to the
      Ikaros family. The GC box was shown to specifically bind Sp1 using extracts from
      LPS-stimulated B cells and A20/2J but not from DC and DC line XS106.
      Additionally, Sp1 transactivated the promoter in A20/2J but not in XS106 cells,
      and mutation of the Sp1 site diminished transactivation. Furthermore, binding of
      the protein complex at the GC box is required for NF-kappaB activity, and the
      spatial alignment of the binding sites is of critical importance for promoter
      activity. Thus, identical and distinct proteins contribute to expression of CCL22
      in DC and B cells.

PMID- 15843562
TI  - Atorvastatin induces T cell anergy via phosphorylation of ERK1.
AB  - Modulation of T cell response is a novel property of 3-hydroxy-3-methylglutaryl
      (HMG)-CoA reductase inhibitors. Previously we reported the benefits of
      atorvastatin treatment in experimental autoimmune encephalomyelitis, the murine
      model of the T cell-mediated autoimmune disorder multiple sclerosis, in which a
      blockade of the T cell cycle by atorvastatin was attributed to an accumulation of
      the negative regulator p27(Kip1). We show in this report that, in line with the
      documented role of p27(Kip1) in T cell anergy, treatment with atorvastatin
      results in a deficient response to a second productive stimulus in human T cells.
      This effect of atorvastatin was dependent on HMG-CoA reduction and required IL-10
      signaling. Importantly, atorvastatin induced an early and sustained
      phosphorylation of ERK1, but not ERK2, which was crucial for the induction of
      anergy. On the basis of the therapeutic impact of HMG-CoA reductase inhibitors,
      the present findings should pave the way for future therapeutic concepts related
      to tolerance induction in neuroinflammatory disorders such as multiple sclerosis.

PMID- 15843563
TI  - Mass tag-assisted identification of naturally processed HLA class II-presented
      meningococcal peptides recognized by CD4+ T lymphocytes.
AB  - The meningococcal class I outer membrane protein porin A plays an important role
      in the development of T cell-dependent protective immunity against meningococcal
      serogroup B infection and is therefore a major component of candidate
      meningococcal vaccines. T cell epitopes from porin A are poorly characterized
      because of weak in vitro memory T cell responses against purified Ag and strain
      variation. We applied a novel strategy to identify relevant naturally processed
      and MHC class II-presented porin A epitopes, based on stable isotope labeling of
      Ag. Human immature HLA-DR1-positive dendritic cells were used for optimal uptake
      and MHC class II processing of (14)N- and (15)N-labeled isoforms of the
      neisserial porin A serosubtype P1.5-2,10 in bacterial outer membrane vesicles.
      HLA-DR1 bound peptides, obtained after 48 h of Ag processing, contained typical
      spectral doublets in mass spectrometry that could easily be assigned to four
      porin A regions, expressed at diverging densities ( approximately 30-4000
      copies/per cell). Epitopes from two of these regions are recognized by HLA-DR1
      restricted CD4(+) T cell lines and are conserved among different serosubtypes of
      meningococcal porin A. This mass tag-assisted approach provides a useful
      methodology for rapid identification of MHC class II presented bacterial CD4(+) T
      cell epitopes relevant for vaccine development.

PMID- 15843564
TI  - Bleomycin-induced E prostanoid receptor changes alter fibroblast responses to
      prostaglandin E2.
AB  - Although PGE(2) is a potent inhibitor of fibroblast function, PGE(2) levels are
      paradoxically elevated in murine lungs undergoing fibrotic responses. Pulmonary
      fibroblasts from untreated mice expressed all four E prostanoid (EP) receptors
      for PGE(2). However, following challenge with the fibrogenic agent, bleomycin,
      fibroblasts showed loss of EP2 expression. Lack of EP2 expression correlated with
      an inability of fibroblasts from bleomycin-treated mice to be inhibited by PGE(2)
      in assays of proliferation or collagen synthesis and blunted cAMP elevations in
      response to PGE(2). PGE(2) was similarly unable to suppress proliferation or
      collagen synthesis in fibroblasts from EP2(-/-) mice despite expression of the
      other EP receptors. EP2(-/-), but not EP1(-/-) or EP3(-/-) mice, showed
      exaggerated fibrotic responses to bleomycin administration in vivo as compared
      with wild-type controls. EP2 loss on fibroblasts was verified in a second model
      of pulmonary fibrosis using FITC. Our results for the first time link EP2
      receptor loss on fibroblasts following fibrotic lung injury to altered
      suppression by PGE(2) and thus identify a novel fibrogenic mechanism.

PMID- 15843565
TI  - Hypermutation rate normalized by chronological time.
AB  - It is generally believed that in cells undergoing Ig somatic hypermutation, more
      cell divisions result in more mutations. This is because DNA synthesis and
      replication is thought to play roles in the known mechanisms-cytidine deamination
      and subsequent conversion to thymidine, uracil-DNA glycosylase-mediated repair,
      mismatch repair, and DNA synthesis by error-prone polymerases. In this study, we
      manipulated the number of cell generations by varying the rate at which cultures
      of a mouse cell line were replenished with fresh medium. We found that the
      frequency of mutants does not necessarily increase with the number of cell
      generations. On the contrary, a greater number of divisions can lead to a lower
      frequency of mutants, indicating that cell division is not a rate-limiting step
      in the hypermutation process. Thus, when comparing mutation rates, we suggest
      that rates are more appropriately expressed as mutations per day than per cell
      generation.

PMID- 15843566
TI  - Multiple products derived from two CCL4 loci: high incidence of a new
      polymorphism in HIV+ patients.
AB  - Human CCL4/macrophage inflammatory protein (MIP)-1beta and CCL3/MIP-1alpha are
      two highly related molecules that belong to a cluster of inflammatory CC
      chemokines located in chromosome 17. CCL4 and CCL3 were formed by duplication of
      a common ancestral gene, generating the SCYA4 and SCYA3 genes which, in turn,
      present a variable number of additional non-allelic copies (SCYA4L and SCYA3L1).
      In this study, we show that both CCL4 loci (SCYA4 and SCYA4L) are expressed and
      alternatively generate spliced variants lacking the second exon. In addition, we
      found that the SCYA4L locus is polymorphic and displays a second allelic variant
      (hereinafter SCYA4L2) with a nucleotide change in the intron 2 acceptor splice
      site compared with the one described originally (hereinafter SCYA4L1). Therefore,
      the pattern of SCYA4L2 transcripts is completely different from that of SCYA4L1,
      since SCYA4L2 uses several new acceptor splice sites and generates nine new
      mRNAs. Furthermore, we analyzed the contribution of each locus (SCYA4 and
      SCYA4L1/L2) to total CCL4 expression in human CD8 T cells by RT-amplified
      fragment length polymorphism and real-time PCR, and we found that L2 homozygous
      individuals (L2L2) only express half the levels of CCL4 compared with L1L1
      individuals. The analysis of transcripts from the SCYA4L locus showed a lower
      level in L2 homozygous compared with L1 homozygous individuals (12% vs 52% of
      total CCL4 transcripts). A possible clinical relevance of these CCL4 allelic
      variants was suggested by the higher frequency of the L2 allele in a group of
      HIV(+) individuals (n = 175) when compared with controls (n = 220, 28.6% vs 16.6%
      (p = 0.00016)).

PMID- 15843567
TI  - Unusually similar patterns of antibody V segment diversity in distantly related
      marsupials.
AB  - A pattern of coevolution between the V gene segments of Ig H and L chains has
      been noted previously by several investigators. Species with restricted germline
      V(H) diversity tend to have limited germline V(L) diversity, whereas species with
      high levels of germline V(H) diversity have more diverse V(L) gene segments.
      Evidence for a limited pool of V(H) but diverse V(L) gene segments in a South
      American opossum, Monodelphis domestica, is consistent with this marsupial being
      an exception to the pattern. To determine whether M. domestica is unique or the
      norm for marsupials, the V(H) and V(L) of an Australian possum, Trichosurus
      vulpecula, were characterized. The Ig repertoire in T. vulpecula is also derived
      from a restricted V(H) pool but a diverse V(L) pool. The V(L) gene segments of T.
      vulpecula are highly complex and contain lineages that predate the separation of
      marsupials and placental mammals. Thus, neither marsupial follows a pattern of
      coevolution of V(H) and V(L) gene segments observed in other mammals. Rather,
      marsupial V(H) and V(L) complexity appears to be evolving divergently, retaining
      diversity in V(L) perhaps to compensate for limited V(H) diversity. There is a
      high degree of similarity between the V(H) and V(L) in M. domestica and T.
      vulpecula, with the majority of V(L) families being shared between both species.
      All marsupial V(H) sequences isolated so far form a common clade of closely
      related sequences, and in contrast to the V(L) genes, the V(H) likely underwent a
      major loss of diversity early in marsupial evolution.

PMID- 15843568
TI  - The secreted peptidyl prolyl cis,trans-isomerase HP0175 of Helicobacter pylori
      induces apoptosis of gastric epithelial cells in a TLR4- and apoptosis signal
      regulating kinase 1-dependent manner.
AB  - Apoptosis contributes to the pathology of gastric epithelial cell damage that
      characterizes Helicobacter pylori infection. The secreted peptidyl prolyl cis,
      trans-isomerase of H. pylori, HP0175 executed apoptosis of the gastric epithelial
      cell line AGS in a dose- and time-dependent manner. The effect of HP0175 was
      confirmed by generating an isogenic mutant of H. pylori disrupted in the HP0175
      gene. The apoptosis-inducing ability of this mutant was impaired compared with
      that of the wild type. The effect of HP0175 was mediated through TLR4.
      Preincubation of the gastric epithelial cell line AGS with anti-TLR4 mAb
      inhibited apoptosis induced by HP0175. Downstream of TLR4, apoptosis signal
      regulating kinase 1 activated MAPK p38, leading to the caspase 8-dependent
      cleavage of Bid, its translocation to the mitochondria, mitochondrial pore
      formation, cytochrome c release, and activation of caspases 9 and 3. We show for
      the first time that a secreted bacterial Ag with peptidyl prolyl cis,trans
      isomerase activity signals through TLR4, and that this Ag executes gastric
      epithelial cell apoptosis through a signaling pathway in which TLR4 and apoptosis
      signal-regulating kinase 1 are central players.

PMID- 15843569
TI  - Infection-induced marginal zone B cell production of Borrelia hermsii-specific
      antibody is impaired in the absence of CD1d.
AB  - Ab that arise in the absence of T cell help are a critical host defense against
      infection with the spirochetes Borrelia burgdorferi and Borrelia hermsii. We have
      previously shown that CD1d-deficient (CD1d(-/-)) mice have impaired resistance to
      infection with B. burgdorferi. In mice, CD1d expression is highest on marginal
      zone B (MZB) cells, which produce Ab to blood-borne Ag. In this study we examined
      MZB cell activation and Ab production in mice infected with B. hermsii, which
      achieve high levels of bacteremia. We show by flow cytometry that MZB cells
      associate with B. hermsii and up-regulate the activation markers syndecan I and
      B7.1 within 16 h of infection. By 24 h, MZB cells secrete B. hermsii-specific
      IgM, coinciding with the loss of activation marker expression and the reduction
      in spirochete burden. In contrast, MZB cells from CD1d(-/-) mice remain activated
      for at least 96 h of infection, but produce only minimal B. hermsii-specific IgM
      in vivo and ex vivo; pathogen burden in the blood also remains elevated. Wild
      type mice depleted of MZB cells using mAb to LFA-1 and alpha(4)beta(1) integrin
      have reduced serum levels of B. hermsii-specific IgM and increased pathogen
      burden, similar to B. hermsii-infected CD1d(-/-) mice. Passive transfer of immune
      mouse serum, but not naive mouse serum, into infected CD1d(-/-) mice leads to
      down-regulation of activation markers and clearance of B. hermsii from the MZB
      cells. These results demonstrate that blood-borne spirochetes activate MZB cells
      to produce pathogen-specific IgM and reveal a role for CD1d in this process.

PMID- 15843570
TI  - Mycobacteria inhibition of IFN-gamma induced HLA-DR gene expression by up
      regulating histone deacetylation at the promoter region in human THP-1 monocytic
      cells.
AB  - Infection of macrophages with mycobacteria has been shown to inhibit the
      macrophage response to IFN-gamma. In the current study, we examined the effect of
      Mycobacteria avium, Mycobacteria tuberculosis, and TLR2 stimulation on IFN-gamma
      induced gene expression in human PMA-differentiated THP-1 monocytic cells.
      Mycobacterial infection inhibited IFN-gamma-induced expression of HLA-DRalpha and
      HLA-DRbeta mRNA and partially inhibited CIITA expression but did not affect
      expression of IFN regulatory factor-1 mRNA. To determine whether inhibition of
      histone deacetylase (HDAC) activity could rescue HLA-DR gene expression, butyric
      acid and MS-275, inhibitors of HDAC activity, were added at the time of M. avium
      or M. tuberculosis infection or TLR2 stimulation. HDAC inhibition restored the
      ability of these cells to express HLA-DRalpha and HLA-DRbeta mRNA in response to
      IFN-gamma. Histone acetylation induced by IFN-gamma at the HLA-DRalpha promoter
      was repressed upon mycobacteria infection or TLR2 stimulation. HDAC gene
      expression was not affected by mycobacterial infection. However, mycobacterial
      infection or TLR2 stimulation up-regulated expression of mammalian Sin3A, a
      corepressor that is required for MHC class II repression by HDAC. Furthermore, we
      show that the mammalian Sin3A corepressor is associated with the HLA-DRalpha
      promoter in M. avium-infected THP-1 cells stimulated with IFN-gamma. Thus,
      mycobacterial infection of human THP-1 cells specifically inhibits HLA-DR gene
      expression by a novel pathway that involves HDAC complex formation at the HLA-DR
      promoter, resulting in histone deacetylation and gene silencing.

PMID- 15843571
TI  - Molecular and functional characterization of NKG2D, NKp80, and NKG2C triggering
      NK cell receptors in rhesus and cynomolgus macaques: monitoring of NK cell
      function during simian HIV infection.
AB  - An involvement of innate immunity and of NK cells during the priming of adaptive
      immune responses has been recently suggested in normal and disease conditions
      such as HIV infection and acute myelogenous leukemia. The analysis of NK cell
      triggering receptor expression has been so far restricted to only NKp46 and NKp30
      in Macaca fascicularis. In this study, we extended the molecular and functional
      characterization to the various NK cell-triggering receptors using PBMC and to
      the in vitro-derived NK cell populations by cytofluorometry and by cytolytic
      activity assays. In addition, RT-PCR strategy, cDNA cloning/sequencing, and
      transient transfections were used to identify and characterize NKp80, NKG2D,
      CD94/NKG2C, and CD94/NKG2A in M. fascicularis and Macaca mulatta as well as in
      the signal transducing polypeptide DNAX-activating protein DAP-10. Both M.
      fascicularis and M. mulatta NK cells express NKp80, NKG2D, and NKG2C molecules,
      which displayed a high degree of sequence homology with their human counterpart.
      Analysis of NK cells in simian HIV-infected M. fascicularis revealed reduced
      surface expression of selected NK cell-triggering receptors associated with a
      decreased NK cell function only in some animals. Overall surface density of NK
      cell-triggering receptors on peripheral blood cells and their triggering function
      on NK cell populations derived in vitro was not decreased compared with
      uninfected animals. Thus, triggering NK cell receptor monitoring on macaque NK
      cells is possible and could provide a valuable tool for assessing NK cell
      function during experimental infections and for exploring possible differences in
      immune correlates of protection in humans compared with cynomolgus and rhesus
      macaques undergoing different vaccination strategies.

PMID- 15843572
TI  - Antibodies against tumor cell glycolipids and proteins, but not mucins, mediate
      complement-dependent cytotoxicity.
AB  - One of several effector mechanisms thought to contribute to Ab efficacy against
      cancer is complement-dependent cytotoxicity (CDC). Serological analysis of a
      series of clinical trials conducted over a 10-year period suggested that six
      vaccines containing different glycolipids induced Abs mediating CDC whereas four
      vaccines containing carbohydrate or peptide epitopes carried almost exclusively
      by mucin molecules induced Abs that did not mediate CDC. To explore this further,
      we have now compared cell surface reactivity using flow cytometry assays (FACS),
      complement-fixing ability, and CDC activity of a panel of mAbs and immune sera
      from these trials on the same two tumor cell lines. Abs against glycolipids GM2,
      globo H and Lewis Y, protein KSA (epithelial cell adhesion molecule, also known
      as EpCAM) and mucin Ags Tn, sialylated Tn, Thomsen Friedenreich (TF), and MUC1
      all reacted comparably by FACS with tumor cells expressing these Ags. Compared
      with the strong complement binding and CDC with Abs against glycolipids and KSA,
      complement binding was diminished with Abs against mucin Ags and no CDC was
      detected. A major difference between these two groups of Ags is proximity to the
      cell membrane. Glycolipids and globular glycoproteins extend less than 100 A from
      the cell membrane while mucins extend up to 5000 A. Although complement
      activation at sites remote from the cell membrane has long been known as a
      mechanism for resistance from complement lysis in bacteria, it is identified here
      for the first time as a factor which may contribute to resistance from CDC
      against cancer cells.

PMID- 15843573
TI  - TLR2 signaling is critical for Mycoplasma pneumoniae-induced airway mucin
      expression.
AB  - Excessive airway mucin production contributes to airway obstruction in lung
      diseases such as asthma and chronic obstructive pulmonary disease. Respiratory
      infections, such as atypical bacterium Mycoplasma pneumoniae (Mp), have been
      proposed to worsen asthma and chronic obstructive pulmonary disease in part
      through increasing mucin. However, the molecular mechanisms involved in infection
      induced airway mucin overexpression remain to be determined. TLRs have been
      recently shown to be a critical component in host innate immune response to
      infections. TLR2 signaling has been proposed to be involved in inflammatory cell
      activation by mycoplasma-derived lipoproteins. In this study, we show that TLR2
      signaling is critical in Mp-induced airway mucin expression in mice and human
      lung epithelial cells. Respiratory Mp infection in BALB/c mice activated TLR2
      signaling and increased airway mucin. A TLR2-neutralizing Ab significantly
      reduced mucin expression in Mp-infected BALB/c mice. Furthermore, Mp-induced
      airway mucin was abolished in TLR2 gene-deficient C57BL/6 mice. Additionally, Mp
      was shown to increase human lung A549 epithelial cell mucin expression, which was
      inhibited by the overexpression of a human TLR2 dominant-negative mutant. These
      results clearly demonstrate that respiratory Mp infection increases airway mucin
      expression, which is dependent on the activation of TLR2 signaling.

PMID- 15843574
TI  - Adaptive immune responses are dispensable for isolated lymphoid follicle
      formation: antigen-naive, lymphotoxin-sufficient B lymphocytes drive the
      formation of mature isolated lymphoid follicles.
AB  - Isolated lymphoid follicles (ILFs) are recently appreciated members of the
      mucosal immune system. The architecture, composition, and inducible nature of
      these structures indicates that these structures are tertiary lymphoid
      structures. The process leading to the formation of tertiary lymphoid structures,
      lymphoid neogenesis, has been observed in a number of inflammatory and autoimmune
      conditions. Given this association, there is considerable interest in identifying
      the factors promoting lymphoid neogenesis, and understanding the steps in this
      process. Using murine ILF formation as a model, we have examined the roles of
      different cellular sources of lymphotoxin (LT) and the adaptive immune response
      in lymphoid neogenesis. In this study, we report that, although other cellular
      sources of LT may supplant B lymphocytes in the formation of immature ILFs
      (loosely organized clusters of B lymphocytes), LT-sufficient B lymphocytes are
      required for the progression of immature ILFs to mature ILFs (organized lymphoid
      aggregates with a follicle-associated epithelium). ILF formation occurs in the
      absence of T lymphocytes and Ag-specific B lymphocyte responses, and ILF B
      lymphocytes express elevated levels of LT in the absence of antigenic
      stimulation. Consistent with a role for chemokines inducing LT expression in Ag
      naive B lymphocytes, and a chemokine-driven positive-feedback loop driving mature
      ILF formation, mature ILFs express elevated levels of B lymphocyte
      chemoattractant in the absence of Ag-specific B lymphocyte stimulation. These
      observations indicate that ILFs contain Ag-naive lymphocytes, and suggest that
      events occurring within ILFs shape subsequent immune responses mediated by these
      lymphocytes.

PMID- 15843575
TI  - A CD8+ T cell heptaepitope minigene vaccine induces protective immunity against
      Chlamydia pneumoniae.
AB  - An intact T cell compartment and IFN-gamma signaling are required for protective
      immunity against Chlamydia. In the mouse model of Chlamydia pneumoniae (Cpn)
      infection, this immunity is critically dependent on CD8(+) T cells. Recently we
      reported that Cpn-infected mice generate an MHC class I-restricted CD8(+) Tc1
      response against various Cpn Ags, and that CD8(+) CTL to multiple epitopes
      inhibit Cpn growth in vitro. Here, we engineered a DNA minigene encoding seven H
      2(b)-restricted Cpn CTL epitopes, the universal pan-DR epitope Th epitope, and an
      endoplasmic reticulum-translocating signal sequence. Immunization of C57BL/6 mice
      with this construct primed IFN-gamma-producing CD8(+) CTL against all seven CTL
      epitopes. CD8(+) T cell lines generated to minigene-encoded CTL epitopes secreted
      IFN-gamma and TNF-alpha and exhibited CTL activity upon recognition of Cpn
      infected macrophages. Following intranasal challenge with Cpn, a 3.6 log
      reduction in mean lung bacterial numbers compared with control animals was
      obtained. Using a 20-fold increase in the Cpn challenging dose, minigene
      vaccinated mice had a 60-fold reduction in lung bacterial loads, compared with
      controls. Immunization and challenge studies with beta(2)-microglobulin(-/-) mice
      indicated that the reduction of lung Cpn burdens was mediated by the MHC class I
      dependent CD8(+) T cells to minigene-included Cpn CTL epitopes, rather than by
      pan-DR epitope-specific CD4(+) T cells. This constitutes the first demonstration
      of significant protection achieved by immunization with a CD8(+) T cell epitope
      based DNA construct in a bacterial system and provides the basis for the optimal
      design of multicomponent anti-Cpn vaccines for humans.

PMID- 15843576
TI  - Novel fibrogenic pathways are activated in response to endothelial apoptosis:
      implications in the pathophysiology of systemic sclerosis.
AB  - Apoptosis of endothelial cells (EC) is appreciated as a primary pathogenic event
      in systemic sclerosis. Yet, how apoptosis of EC leads to fibrosis remains to be
      determined. We report that apoptosis of EC triggers the release of novel
      fibrogenic mediators. Medium conditioned by apoptotic EC (SSC) was found to
      inhibit apoptosis of fibroblasts, whereas medium conditioned by EC in which
      apoptosis was blocked (with either pan-caspase inhibition or Bcl-x(L)
      overexpression) did not. PI3K was activated in fibroblasts exposed to SSC. This
      was associated with downstream repression of Bim-EL and long-term up-regulation
      of Bcl-x(L) protein levels. RNA interference for Bim-EL in fibroblasts blocked
      apoptosis. SSC also induced PI3K-dependent myofibroblast differentiation with
      expression of alpha-smooth muscle actin, formation of stress fibers, and
      production of collagen I. A C-terminal fragment of the domain V of perlecan was
      identified as one of the fibrogenic mediators present in SSC. A synthetic peptide
      containing an EGF motif present on the perlecan fragment and chondroitin 4
      sulfate, a glycosaminoglycan anchored on the domain V of perlecan, induced PI3K
      dependent resistance to apoptosis in fibroblasts and myofibroblast
      differentiation. Human fibroblasts derived from sclerodermic skin lesions were
      more sensitive to the antiapoptotic activities of the synthetic peptide and
      chondroitin 4-sulfate than fibroblasts derived from normal controls. Hence, we
      propose that a chronic increase in endothelial apoptosis and/or increased
      sensitivity of fibroblasts to mediators produced by apoptotic EC could form the
      basis of a fibrotic response characterized by sustained induction of an
      antiapoptotic phenotype in fibroblasts and persistent myofibroblast
      differentiation.

PMID- 15843577
TI  - Complement inhibitors targeted to the proximal tubule prevent injury in
      experimental nephrotic syndrome and demonstrate a key role for C5b-9.
AB  - In glomerular diseases of diverse etiologies, dysfunction of the glomerular
      barrier to protein passage results in proteinuria, and proteinuria is considered
      an independent risk factor that plays a direct role in inflammation, interstitial
      fibrosis, and renal failure. The mechanism by which proteinuria leads to
      nephrotoxic injury is unclear, but a role for complement in mediating
      interstitial damage appears likely. We describe a strategy for Ag-specific
      targeting of complement inhibitors using a single chain Ab fragment and show that
      complement inhibitors targeted to the tubular epithelium protect against
      tubulointerstitial injury and renal dysfunction in a rat model of puromycin
      induced nephrosis. The targeting of systemically administered complement
      inhibitors markedly enhanced their efficacy and obviated the need to systemically
      inhibit complement, thus reducing the risk of compromising host defense and
      immune homeostasis. Targeted inhibition of complement activation by Crry, and of
      membrane attack complex (MAC) formation by CD59 was equally therapeutic,
      demonstrating that the MAC plays a key role in proteinuria-induced
      tubulointerstitial injury. CD59 activity was dependent on its being targeted to
      the site of complement activation, and this is the first report of specific
      inhibition of the MAC in vivo after systemic administration of inhibitor. The
      data establish the MAC is a valid target for pharmaceutical intervention in
      proteinuric disorders and provide an approach to investigate the role of the MAC
      in complement-dependent disease under clinically relevant conditions.

PMID- 15843578
TI  - Endogenous attenuation of allergic lung inflammation by syndecan-1.
AB  - The airway plays a vital role in allergic lung diseases by responding to inhaled
      allergens and initiating allergic inflammation. Various proinflammatory functions
      of the airway epithelium have been identified, but, equally important, anti
      inflammatory mechanisms must also exist. We show in this study that syndecan-1,
      the major heparan sulfate proteoglycan of epithelial cells, attenuates allergic
      lung inflammation. Our results show that syndecan-1-null mice instilled with
      allergens exhibit exaggerated airway hyperresponsiveness, glycoprotein
      hypersecretion, eosinophilia, and lung IL-4 responses. However, administration of
      purified syndecan-1 ectodomains, but not ectodomain core proteins devoid of
      heparan sulfate, significantly inhibits these inflammatory responses.
      Furthermore, syndecan-1 ectodomains are shed into the airway when wild-type mice
      are intranasally instilled with several biochemically distinct inducers of
      allergic lung inflammation. Our results also show that syndecan-1 ectodomains
      bind to the CC chemokines (CCL7, CCL11, and CCL17) implicated in allergic
      diseases, inhibit CC chemokine-mediated T cell migration, and suppress allergen
      induced accumulation of Th2 cells in the lung through their heparan sulfate
      chains. Together, these findings uncover an endogenous anti-inflammatory
      mechanism of the airway epithelium where syndecan-1 ectodomains attenuate
      allergic lung inflammation via suppression of CC chemokine-mediated Th2 cell
      recruitment to the lung.

PMID- 15843579
TI  - Gene therapy to manipulate effector T cell trafficking to tumors for
      immunotherapy.
AB  - Strategies that generate tumor Ag-specific effector cells do not necessarily cure
      established tumors. We hypothesized that the relative efficiency with which tumor
      specific effector cells reach the tumor is critical for therapy. We demonstrate
      in this study that activated T cells respond to the chemokine CCL3, both in vitro
      and in vivo, and we further demonstrate that expression of CCL3 within tumors
      increases the effector T cell infiltrate in those tumors. Importantly, we show
      that adenoviral gene transfer to cause expression of CCL3 within B16ova tumors in
      vivo increases the efficacy of adoptive transfer of tumor-specific effector OT1 T
      cells. We additionally demonstrate that such therapies result in endogenous
      immune responses to tumor Ags that are capable of protecting animals against
      subsequent tumor challenge. Strategies that modify the "visibility" of tumors
      have the potential to significantly enhance the efficacy of both vaccine and
      adoptive transfer therapies currently in development.

PMID- 15843580
TI  - Manipulation of allergen-induced airway remodeling by treatment with anti-TGF
      beta antibody: effect on the Smad signaling pathway.
AB  - Airway inflammation and remodeling are important pathophysiologic features of
      chronic asthma. Previously, we have developed a mouse model of prolonged allergen
      challenge which exhibits many characteristics of chronic asthma such as goblet
      cell hyperplasia and subepithelial collagen deposition, in association with an
      increase in lung expression of the profibrotic mediator, TGF-beta. The aim of
      this study was to determine the effects of blockade of TGF-beta on the
      development of airway inflammation and remodeling using our murine model of
      prolonged allergen challenge. Importantly anti-TGF-beta Ab was administered
      therapeutically, with dosing starting after the onset of established eosinophilic
      airway inflammation. Therapeutic treatment of mice with anti-TGF-beta Ab
      significantly reduced peribronchiolar extracellular matrix deposition, airway
      smooth muscle cell proliferation, and mucus production in the lung without
      affecting established airway inflammation and Th2 cytokine production. Thus, our
      data suggest that it might be possible to uncouple airway inflammation and
      remodeling during prolonged allergen challenge. In addition, anti-TGF-beta Ab
      treatment was shown to regulate active TGF-beta signaling in situ with a
      reduction in the expression of phospho-Smad 2 and the concomitant up-regulation
      of Smad 7 in lung sections. Therefore, this is the first report to suggest that
      anti-TGF-beta Ab treatment prevents the progression of airway remodeling
      following allergen challenge even when given in a therapeutic mode. Moreover, the
      molecular mechanism behind this effect may involve regulation of active TGF-beta
      signaling.

PMID- 15843581
TI  - NF-kappa B mediates the stimulation of cytokine and chemokine expression by human
      articular chondrocytes in response to fibronectin fragments.
AB  - Fibronectin fragments (FN-f) that bind to the alpha(5)beta(1) integrin stimulate
      chondrocyte-mediated cartilage destruction and could play an important role in
      the progression of arthritis. The objective of this study was to identify
      potential cytokine mediators of cartilage inflammation and destruction induced by
      FN-f and to investigate the mechanism of their stimulation. Human articular
      chondrocytes, isolated from normal ankle cartilage obtained from tissue donors,
      were treated with a 110-kDa FN-f in serum-free culture, and expression of various
      cytokine genes was analyzed by cDNA microarray and by a cytokine protein array.
      Compared with untreated control cultures, stimulation by FN-f resulted in a >2
      fold increase in IL-6, IL-8, MCP-1, and growth-related oncogene beta (GRO-beta).
      Constitutive and FN-f-inducible expression of GRO-alpha and GRO-gamma were also
      noted by RT-PCR and confirmed by immunoblotting. Previous reports of IL-1beta
      expression induced by FN-f were also confirmed, while TNF expression was found to
      be very low. Inhibitor studies revealed that FN-f-induced stimulation of
      chondrocyte chemokine expression was dependent on NF-kappaB activity, but
      independent of IL-1 autocrine signaling. The ability of FN-f to stimulate
      chondrocyte expression of multiple proinflammatory cytokines and chemokines
      suggests that damage to the cartilage matrix is capable of inducing a
      proinflammatory state responsible for further progressive matrix destruction,
      which also includes the chemoattraction of inflammatory cells. Targeting the
      signaling pathways activated by FN-f may be an effective means of inhibiting
      production of multiple mediators of cartilage destruction.

PMID- 15843582
TI  - Resistin, an adipokine with potent proinflammatory properties.
AB  - The adipokine resistin is suggested to be an important link between obesity and
      insulin resistance. In the present study, we assessed the impact of resistin as
      inflammatogenic cytokine in the setting of arthritis. In vitro experiments on
      human PBMC were performed to assess cytokine response and transcription pathways
      of resistin-induced inflammation. Proinflammatory properties of resistin were
      evaluated in animal model by intra-articular injection of resistin followed by
      histological evaluation of the joint. Levels of resistin were assessed by ELISA
      in 74 paired blood and synovial fluid samples of patients with rheumatoid
      arthritis. Results were compared with the control group comprised blood samples
      from 34 healthy individuals and 21 synovial fluids from patients with
      noninflammatory joint diseases. We now show that resistin displays potent
      proinflammatory properties by 1) strongly up-regulating IL-6 and TNF-alpha, 2)
      responding to TNF-alpha challenge, 3) enhancing its own activity by a positive
      feedback, and finally 4) inducing arthritis when injected into healthy mouse
      joints. Proinflammatory properties of resistin were abrogated by NF-kappaB
      inhibitor indicating the importance of NF-kappaB signaling pathway for resistin
      induced inflammation. Resistin is also shown to specifically accumulate in the
      inflamed joints of patients with rheumatoid arthritis and its levels correlate
      with other markers of inflammation. Our results indicate that resistin is a new
      and important member of the cytokine family with potent regulatory functions.
      Importantly, the identified properties of resistin make it a novel and
      interesting therapeutic target in chronic inflammatory diseases such as
      rheumatoid arthritis.

PMID- 15843583
TI  - Neuropeptide release from dental pulp cells by RgpB via proteinase-activated
      receptor-2 signaling.
AB  - Dental pulp inflammation often results from dissemination of periodontitis caused
      mostly by Porphyromonas gingivalis infection. Calcitonin gene-related peptide and
      substance P are proinflammatory neuropeptides that increase in inflamed pulp
      tissue. To study an involvement of the periodontitis pathogen and neuropeptides
      in pulp inflammation, we investigated human dental pulp cell neuropeptide release
      by arginine-specific cysteine protease (RgpB), a cysteine proteinase of P.
      gingivalis, and participating signaling pathways. RgpB induced neuropeptide
      release from cultured human pulp cells (HPCs) in a proteolytic activity-dependent
      manner at a range of 12.5-200 nM. HPCs expressed both mRNA and the products of
      calcitonin gene-related peptide, substance P, and proteinase-activated receptor-2
      (PAR-2) that were also found in dental pulp fibroblast-like cells. The PAR-2
      agonists, SLIGKV and trypsin, also induced neuropeptide release from HPCs, and
      HPC PAR-2 gene knockout by transfection of PAR-2 antisense oligonucleotides
      inhibited significantly the RgpB-elicited neuropeptide release. These results
      indicated that RgpB-induced neuropeptide release was dependent on PAR-2
      activation. The kinase inhibitor profile on the RgpB-neuropeptide release from
      HPC revealed a new PAR-2 signaling pathway that was mediated by p38 MAPK and
      activated transcription factor-2 activation, in addition to the PAR-2-p44/42
      p38MAPK and -AP-1 pathway. This new RgpB activity suggests a possible link
      between periodontitis and pulp inflammation, which may be modulated by
      neuropeptides released in the lesion.

PMID- 15843584
TI  - Efficient recruitment of lymphocytes in inflamed brain venules requires
      expression of cutaneous lymphocyte antigen and fucosyltransferase-VII.
AB  - Lymphocyte migration into the brain represents a critical event in the
      pathogenesis of multiple sclerosis and its animal model, experimental autoimmune
      encephalomyelitis (EAE). However, the mechanisms controlling the recruitment of
      lymphocytes to the CNS via inflamed brain venules are poorly understood, and
      therapeutic approaches to inhibit this process are consequently few. In this
      study, we demonstrate for the first time that human and murine Th1 lymphocytes
      preferentially adhere to murine inflamed brain venules in an experimental model
      that mimics early inflammation during EAE. A virtually complete inhibition of
      rolling and arrest of Th1 cells in inflamed brain venules was observed with a
      blocking anti-P-selectin glycoprotein ligand 1 Ab and anti-E- and P-selectin Abs.
      Th1 lymphocytes produced from fucosyltransferase (FucT)-IV(-/-) mice efficiently
      tethered and rolled, whereas in contrast, primary adhesion of Th1 lymphocytes
      obtained from FucT-VII(-/-) or Fuc-VII(-/-)FucT-IV(-/-) mice was drastically
      reduced, indicating that FucT-VII is critical for the recruitment of Th1 cells in
      inflamed brain microcirculation. Importantly, we show that Abs directed against
      cutaneous lymphocyte Ag (CLA), a FucT-VII-dependent carbohydrate modification of
      P-selectin glycoprotein ligand 1, blocked rolling of Th1 cells. By exploiting a
      system that allowed us to obtain Th1 and Th2 cells with skin- vs gut-homing
      (CLA(+) vs integrin beta(7)(+)) phenotypes, we observed that induced expression
      of CLA on Th cells determined a striking increase of rolling efficiency in
      inflamed brain venules. These observations allow us to conclude that efficient
      recruitment of activated lymphocytes to the brain in the contexts mimicking EAE
      is controlled by FucT-VII and its cognate cell surface Ag CLA.

PMID- 15843585
TI  - Defects in CD8+ regulatory T cells in the lamina propria of patients with
      inflammatory bowel disease.
AB  - Mucosal tolerance is believed to be partly mediated by regulatory T cells.
      Intestinal epithelial cells (IECs) may play an important role in the generation
      of such regulatory cells, because they are able to process and present Ag to T
      cells. Furthermore, we have previously demonstrated that IECs are able to
      generate regulatory CD8(+) T cells in vitro. In the present study, we have
      analyzed lamina propria (LP) lymphocytes for the presence of such regulatory
      CD8(+) T cells in normal individuals as well as in patients with inflammatory
      bowel disease (IBD). The results of the present study show that LP CD8(+) T cells
      derived from normal controls possess regulatory activity, whereas both
      unfractionated LP lymphocytes and purified LP CD4(+) T cells do not. The LP
      CD8(+) T cells suppress Ig production by pokeweed mitogen-stimulated PBMCs by 31
      80%, in a cell contact-dependent manner. No significant difference in suppression
      between CD28(+) and CD28(-)CD8(+) LP T cells was observed. In contrast to CD8(+)
      T cells from normal LP, CD8(+) T cells isolated from LP of IBD patients, did not
      suppress Ig production by pokeweed mitogen-stimulated PBMC (five of six
      ulcerative colitis specimens; six of six Crohn's disease specimens). Furthermore,
      we demonstrate that the frequency of TCR Vbeta5.1-positive CD8(+) T cells, which
      we previously have demonstrated to be regulatory and to be expanded by IECs in
      vitro, is decreased in IBD LP compared with normal LP. In conclusion, this study
      demonstrates that CD8(+) T cells with regulatory activity are present in the LP
      of normal healthy individuals, but not in patients with IBD, suggesting that
      these cells might play an active role in mucosal tolerance.

PMID- 15843586
TI  - Inhibition of mammalian target of rapamycin potentiates thrombin-induced
      intercellular adhesion molecule-1 expression by accelerating and stabilizing NF
      kappa B activation in endothelial cells.
AB  - We addressed the regulatory function of mammalian target of rapamycin (mTOR) in
      the mechanism of thrombin-induced ICAM-1 gene expression in endothelial cells.
      Pretreatment of HUVECs with rapamycin, an inhibitor of mTOR, augmented thrombin
      induced ICAM-1 expression. Inhibition of mTOR by this approach promoted whereas
      over-expression of mTOR inhibited thrombin-induced transcriptional activity of NF
      kappaB, an essential regulator of ICAM-1 transcription. Analysis of the NF-kappaB
      signaling pathway revealed that inhibition of mTOR potentiated IkappaB kinase
      activation resulting in a rapid and persistent phosphorylation of IkappaBalpha on
      Ser32 and Ser36, a requirement for IkappaBalpha degradation. Consistent with
      these data, we observed a more efficient and stable nuclear localization of
      RelA/p65 and, subsequently, the DNA binding activity of NF-kappaB by thrombin
      following mTOR inhibition. These data define a novel role of mTOR in down
      regulating thrombin-induced ICAM-1 expression in endothelial cells by controlling
      a delayed and transient activation of NF-kappaB.

PMID- 15843587
TI  - Characterization of the anti-tissue transglutaminase antibody response in
      nonobese diabetic mice.
AB  - Type 1 diabetes mellitus is an autoimmune disorder characterized by destruction
      of insulin-producing pancreatic beta cells by T lymphocytes. In nonobese diabetic
      (NOD) mice, a role has been hypothesized for dietary gluten proteins in the onset
      of diabetes, and because gluten dependence is the major feature of celiac
      disease, together with production of Abs to the autoantigen tissue
      transglutaminase (tTG), we looked for the presence of anti-tTG Abs in the serum
      of NOD mice and, to establish their origin, analyzed the Ab repertoire of NOD
      mice using phage display Ab libraries. We found significant levels of serum anti
      tTG Abs and were able to isolate single-chain Ab fragments to mouse tTG mainly
      from the Ab libraries made from intestinal lymphocytes and to a lesser extent
      from splenocytes. Data from NOD mice on a gluten-free diet suggest that the anti
      tTG response is not gluten-dependent. The intestinal Ab response to tTG is a
      feature of NOD mice, but the underlying mechanisms remain obscure.

PMID- 15843588
TI  - Gene expression profiling of the effect of high-dose intravenous Ig in patients
      with Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute vasculitis of infants and young children,
      preferentially affecting the coronary arteries. Intravenous infusion of high dose
      Ig (IVIG) effectively reduces systemic inflammation and prevents coronary artery
      lesions in KD. To investigate the mechanisms underlying the therapeutic effects
      of IVIG, we examined gene expression profiles of PBMC and purified monocytes
      obtained from acute patients before and after IVIG therapy. The results suggest
      that IVIG suppresses activated monocytes and macrophages by altering various
      functional aspects of the genes of KD patients. Among the 18 commonly decreased
      transcripts in both PBMC and purified monocytes, we selected six genes, FCGR1A,
      FCGR3A, CCR2, ADM, S100A9, and S100A12, and confirmed the microarray results by
      real-time RT-PCR. Moreover, the expressions of FcgammaRI and FcgammaRIII on
      monocytes were reduced after IVIG. Plasma S100A8/A9 heterocomplex, but not
      S100A9, levels were elevated in patients with acute KD compared with those in
      febrile controls. Furthermore, S100A8/A9 was rapidly down-regulated in response
      to IVIG therapy. Persistent elevation of S100A8/A9 after IVIG was found in
      patients who later developed coronary aneurysms. These results indicate that the
      effects of IVIG in KD may be mediated by suppression of an array of immune
      activation genes in monocytes, including those activating FcgammaRs and the
      S100A8/A9 heterocomplex.

PMID- 15843589
TI  - Arginine-rich anti-vascular endothelial growth factor (anti-VEGF) hexapeptide
      inhibits collagen-induced arthritis and VEGF-stimulated productions of TNF-alpha
      and IL-6 by human monocytes.
AB  - Vascular endothelial growth factor (VEGF) has been suggested to play a critical
      role in the pathogenesis of rheumatoid arthritis (RA). We previously identified a
      novel RRKRRR hexapeptide that blocked the interaction between VEGF and its
      receptor through the screening of peptide libraries. In this study, we
      investigated whether anti-VEGF peptide RRKRRR (dRK6) could suppress collagen
      induced arthritis (CIA) and regulate the activation of mononuclear cells of RA
      patients. A s.c. injection of dRK6 resulted in a dose-dependent decrease in the
      severity and incidence of CIA and suppressed synovial infiltration of
      inflammatory cells in DBA/1 mice. In these mice, the T cell responses to type II
      collagen (CII) in lymph node cells and circulating IgG Abs to CII were also dose
      dependently inhibited by the peptides. In addition, VEGF directly increased the
      production of TNF-alpha and IL-6 from human PBMC. Synovial fluid mononuclear
      cells of RA patients showed a greater response to VEGF stimulation than the PBMC
      of healthy controls. The major cell types responding to VEGF were monocytes.
      Moreover, anti-VEGF dRK6 inhibited the VEGF-induced production of TNF-alpha and
      IL-6 from synovial fluid mononuclear cells of RA patients and decreased serum IL
      6 levels in CIA mice. In summary, we observed first that dRK6 suppressed the
      ongoing paw inflammation in mice and blocked the VEGF-induced production of
      proinflammatory cytokines. These data suggest that dRK6 may be an effective
      strategy in the treatment of RA, and could be applied to modulate various chronic
      VEGF-dependent inflammatory diseases.

PMID- 15843590
TI  - CXC chemokine ligand 12 (stromal cell-derived factor 1 alpha) and CXCR4-dependent
      migration of CTLs toward melanoma cells in organotypic culture.
AB  - Studies in experimental animal models have demonstrated that chemokines produced
      by tumor cells attract chemokine receptor-positive T lymphocytes into the tumor
      area, which may lead to tumor growth inhibition in vitro and in vivo. However, in
      cancer patients, the role of chemokines in T lymphocyte trafficking toward human
      tumor cells is relatively unexplored. In the present study, the role of
      chemokines and their receptors in the migration of a melanoma patient's CTL
      toward autologous tumor cells has been studied in a novel organotypic melanoma
      culture, consisting of a bottom layer of collagen type I with embedded
      fibroblasts followed successively by a tumor cell layer, collagen/fibroblast
      separating layer, and, finally, a top layer of collagen with embedded fibroblasts
      and T cells. In this model, CTL migrated from the top layer through the
      separating layer toward tumor cells, resulting in tumor cell apoptosis. CTL
      migration was mediated by chemokine receptor CXCR4 expressed by the CTL and
      CXCL12 (stromal cell-derived factor 1alpha) secreted by tumor cells, as evidenced
      by blockage of CTL migration by Abs to CXCL12 or CXCR4, high concentrations of
      CXCL12 or small molecule CXCR4 antagonist. These studies, together with studies
      in mice indicating regression of CXCL12-transduced tumor cells, followed by
      regression of nontransduced challenge tumor cells, suggest that CXCL12 may be
      useful as an immunotherapeutic agent for cancer patients, when transduced into
      tumor cells, or fused to anti-tumor Ag Ab or tumor Ag.

PMID- 15843591
TI  - Induction and inhibition of the Th2 phenotype spread: implications for childhood
      asthma.
AB  - The interactions between genetic and environmental factors play a major role in
      the development of childhood asthma. We hypothesized that a pre-existing
      Th2/asthmatic response can promote Th2 responses to newly encountered Ags (i.e.,
      phenotype spread). To test this hypothesis, we developed a mouse model in which
      the requirements for the induction and inhibition of phenotype spread to a
      clinically relevant neo-allergen (i.e., ragweed) were investigated. Our results
      indicate that 1) phenotype spread to the neo-allergen can be induced only within
      the first 8 h after a bronchial challenge with the first Ag (OVA); 2) Th2
      differentiation of naive CD4(+) T cells occurs in bronchial lymph nodes; 3)
      trafficking of naive CD4(+) T cells to local lymph nodes and IL-4 produced by OVA
      activated Th2 cells play essential roles in the differentiation of naive CD4(+) T
      cells to Th2 cells; and 4) suppression of the production of chemokines involved
      in the homing of naive CD4(+) T and Th2 cells to bronchial lymph nodes by a TLR9
      agonist inhibited phenotype spread and abrogated the consequent development of
      experimental asthma. These findings provide a mechanistic insight into Th2
      phenotype spread and offer an animal model for testing relevant immunomodulatory
      interventions.

PMID- 15843592
TI  - Spatio-temporal modeling of localized brain activity.
AB  - Functional neuroimaging, including positron emission tomography (PET) and
      functional magnetic resonance imaging (fMRI), plays an important role in
      identifying specific brain regions associated with experimental stimuli or
      psychiatric disorders such as schizophrenia. PET and fMRI produce massive data
      sets that contain both temporal correlations from repeated scans and complex
      spatial correlations. Several methods exist for handling temporal correlations,
      some of which rely on transforming the response data to induce either a known or
      an independence covariance structure. Despite the presence of spatial
      correlations between the volume elements (voxels) comprising a brain scan,
      conventional methods perform voxel-by-voxel analyses of measured brain activity.
      We propose a two-stage spatio-temporal model for the estimation and testing of
      localized activity. Our second-stage model specifies a spatial auto-regression,
      capturing correlations within neural processing clusters defined by a data-driven
      cluster analysis. We use maximum likelihood methods to estimate parameters from
      our spatial autoregressive model. Our model protects against type-I errors,
      enables the detection of both localized and regional activations (including
      volume of interest effects), provides information on functional connectivity in
      the brain, and establishes a framework to produce spatially smoothed maps of
      distributed brain activity for each individual. We illustrate the application of
      our model using PET data from a study of working memory in individuals with
      schizophrenia.

PMID- 15843593
TI  - Generalized spatial structural equation models.
AB  - It is common in public health research to have high-dimensional, multivariate,
      spatially referenced data representing summaries of geographic regions. Often, it
      is desirable to examine relationships among these variables both within and
      across regions. An existing modeling technique called spatial factor analysis has
      been used and assumes that a common spatial factor underlies all the variables
      and causes them to be related to one another. An extension of this technique
      considers that there may be more than one underlying factor, and that
      relationships among the underlying latent variables are of primary interest.
      However, due to the complicated nature of the covariance structure of this type
      of data, existing methods are not satisfactory. We thus propose a generalized
      spatial structural equation model. In the first level of the model, we assume
      that the observed variables are related to particular underlying factors. In the
      second level of the model, we use the structural equation method to model the
      relationship among the underlying factors and use parametric spatial
      distributions on the covariance structure of the underlying factors. We apply the
      model to county-level cancer mortality and census summary data for Minnesota,
      including socioeconomic status and access to public utilities.

PMID- 15843594
TI  - Processive lipid galactosyl/glucosyltransferases from Agrobacterium tumefaciens
      and Mesorhizobium loti display multiple specificities.
AB  - The glycosyltransferase family 21 (GT21) includes both enzymes of eukaryotic and
      prokaryotic organisms. Many of the eukaryotic enzymes from animal, plant, and
      fungal origin have been characterized as uridine diphosphoglucose (UDP
      Glc):ceramide glucosyltransferases (glucosylceramide synthases [Gcs], EC
      2.4.1.80). As the acceptor molecule ceramide is not present in most bacteria, the
      enzymatic specificities and functions of the corresponding bacterial
      glycosyltransferases remain elusive. In this study, we investigated the
      homologous and heterologous expression of GT21 enzymes from Agrobacterium
      tumefaciens and Mesorhizobium loti in A. tumefaciens, Escherichia coli, and the
      yeast Pichia pastoris. Glycolipid analyses of the transgenic organisms revealed
      that the bacterial glycosyltransferases are involved in the synthesis of mono-,
      di- and even tri-glycosylated glycolipids. As products resulting from their
      activity, we identified 1,2-diacyl-3-(O-beta-D-galacto-pyranosyl)-sn-glycerol,
      1,2-diacyl-3-(O-beta-D-gluco-pyranosyl)-sn-glycerol as well as higher
      glycosylated lipids such as 1,2-diacyl-3-[O-beta-D-galacto-pyranosyl-(1-->6)-O
      beta-D-galacto-pyranosyl]-sn-glycerol, 1,2-diacyl-3-[O-beta-D-gluco-pyranosyl-(1-
      >6)-O-beta-D-galacto-pyranosyl]-sn-glycerol, 1,2-diacyl-3-[O-beta-D-gluco
      pyranosyl-(1-->6)-O-beta-D-gluco-pyranosyl]-sn-glycerol, and the deviatingly
      linked diglycosyldiacylglycerol 1,2-diacyl-3-[O-beta-D-gluco-pyranosyl-(1-->3)-O
      beta-D-galacto-pyranosyl]-sn-glycerol. From a mixture of
      triglycosyldiacylglycerols, 1,2-diacyl-3-[O-beta-D-galacto-pyranosyl-(1-->6)-O
      beta-D-galacto-pyranosyl-(1-->6)-O-beta-D-galacto-pyranosyl]-sn-glycerol could be
      separated in a pure form. In vitro enzyme assays showed that the
      glycosyltransferase from A. tumefaciens favours uridine diphosphogalactose (UDP
      Gal) over UDP-Glc. In conclusion, the bacterial GT21 enzymes differ from the
      eukaryotic ceramide glucosyltransferases by the successive transfer of up to
      three galactosyl and glucosyl moieties to diacylglycerol.

PMID- 15843595
TI  - Modeling bacterial UDP-HexNAc: polyprenol-P HexNAc-1-P transferases.
AB  - Protein N-glycosylation in eukaryotes and peptidoglycan biosynthesis in bacteria
      are both initiated by the transfer of a D-N-acetylhexosamine 1-phosphate to a
      membrane-bound polyprenol phosphate. These reactions are catalyzed by a family of
      transmembrane proteins known as the UDP-D-N-acetylhexosamine: polyprenol
      phosphate D-N-acetylhexosamine 1-phosphate transferases. The sole eukaryotic
      member of this family, the d-N-acetylglucosamine 1-phosphate transferase (GPT),
      is specific for UDP-GlcNAc as the donor substrate and uses dolichol phosphate as
      the membrane-bound acceptor. The bacterial translocases, MraY, WecA, and WbpL,
      utilize undecaprenol phosphate as the acceptor substrate, but differ in their
      specificity for the UDP-sugar donor substrate. The structural basis of this sugar
      nucleotide specificity is uncertain. However, potential carbohydrate recognition
      (CR) domains have been identified within the C-terminal cytoplasmic loops of
      MraY, WecA, and WbpL that are highly conserved in family members with the same
      UDP-N-acetylhexosamine specificity. This review focuses on the catalytic
      mechanism and substrate specificity of these bacterial UDP-D-N-acetylhexosamine:
      polyprenol phosphate D-N-acetylhexosamine 1-P transferases and may provide
      insights for the development of selective inhibitors of cell wall biosynthesis.

PMID- 15843596
TI  - Compositional profiling of heparin/heparan sulfate using mass spectrometry: assay
      for specificity of a novel extracellular human endosulfatase.
AB  - An important class of carbohydrates studied within the field of glycobiology,
      heparin and heparan sulfate (HS) have been implicated in a diverse array of
      biological functions. Changes in their sulfation pattern and domain organization
      have been associated with different pathological situations such as viral
      infectivity, tumor growth, and metastasis. To obtain structural information about
      these biomolecules, and the modifications they may undergo during different
      stages of cell growth and development, a mass spectrometry-based method was
      developed and used to obtain unambiguous structural information on the
      glycosaminoglycans (GAGs) that comprise heparin/HS. The method was applied to
      assay for the heparin substrate specificity of a newly discovered human
      extracellular endosulfatase, HSulf-2, which has been implicated in tumorigenesis.
      This new protocol incorporates 12 known heparin disaccharides, including three
      sets of isomers. A unique response factor (R) is determined for each
      disaccharide, whereas a multiplexed and data processing method is incorporated
      for faster data acquisition and quantification purposes. Proof of principle was
      performed by using various heparin/HS samples isolated from bovine and porcine
      tissues.

PMID- 15843597
TI  - The animal sialyltransferases and sialyltransferase-related genes: a phylogenetic
      approach.
AB  - The animal sialyltransferases are Golgi type II transmembrane
      glycosyltransferases. Twenty distinct sialyltransferases have been identified in
      both human and murine genomes. These enzymes catalyze transfer of sialic acid
      from CMP-Neu5Ac to the glycan moiety of glycoconjugates. Despite low overall
      identities, they share four conserved peptide motifs [L (large), S (small), motif
      III, and motif VS (very small)] that are hallmarks for sialyltransferase
      identification. We have identified 155 new putative genes in 25 animal species,
      and we have exploited two lines of evidence: (1) sequence comparisons and (2)
      exon-intron organization of the genes. An ortholog to the ancestor present before
      the split of ST6Gal I and II subfamilies was detected in arthropods. An ortholog
      to the ancestor present before the split of ST6GalNAc III, IV, V, and VI
      subfamilies was detected in sea urchin. An ortholog to the ancestor present
      before the split of ST3Gal I and II subfamilies was detected in ciona, and an
      ortholog to the ancestor of all the ST8Sia was detected in amphioxus. Therefore,
      single examples of the four families (ST3Gal, ST6Gal, ST6GalNAc, and ST8Sia) have
      appeared in invertebrates, earlier than previously thought, whereas the four
      families were all detected in bony fishes, amphibians, birds, and mammals. As
      previously hypothesized, sequence similarities among sialyltransferases suggest a
      common genetic origin, by successive duplications of an ancestral gene, followed
      by divergent evolution. Finally, we propose predictions on these invertebrates
      sialyltransferase-related activities that have not previously been demonstrated
      and that will ultimately need to be substantiated by protein expression and
      enzymatic activity assays.

PMID- 15843598
TI  - A secondary structural model of the 28S rRNA expansion segments D2 and D3 for
      Chalcidoid wasps (Hymenoptera: Chalcidoidea).
AB  - We analyze the secondary structure of two expansion segments (D2, D3) of the 28S
      ribosomal (rRNA)-encoding gene region from 527 chalcidoid wasp taxa (Hymenoptera:
      Chalcidoidea) representing 18 of the 19 extant families. The sequences are
      compared in a multiple sequence alignment, with secondary structure inferred
      primarily from the evidence of compensatory base changes in conserved helices of
      the rRNA molecules. This covariation analysis yielded 36 helices that are
      composed of base pairs exhibiting positional covariation. Several additional
      regions are also involved in hydrogen bonding, and they form highly variable base
      pairing patterns across the alignment. These are identified as regions of
      expansion and contraction or regions of slipped-strand compensation.
      Additionally, 31 single-stranded locales are characterized as regions of
      ambiguous alignment based on the difficulty in assigning positional homology in
      the presence of multiple adjacent indels. Based on comparative analysis of these
      sequences, the largest genetic study on any hymenopteran group to date, we report
      an annotated secondary structural model for the D2, D3 expansion segments that
      will prove useful in assigning positional nucleotide homology for phylogeny
      reconstruction in these and closely related apocritan taxa.

PMID- 15843599
TI  - Degeneration and domestication of a selfish gene in yeast: molecular evolution
      versus site-directed mutagenesis.
AB  - VDE is a homing endonuclease gene in yeasts with an unusual evolutionary history
      including horizontal transmission, degeneration, and domestication into the
      mating-type switching locus HO. We investigate here the effects of these features
      on its molecular evolution. In addition, we correlate rates of evolution with
      results from site-directed mutagenesis studies. Functional elements have lower
      rates of evolution than degenerate ones and higher conservation at functionally
      important sites. However, functionally important and unimportant sites are
      equally likely to have been involved in the evolution of new function during the
      domestication of VDE into HO. The domestication event also indicates that VDE has
      been lost in some species and that VDE has been present in yeasts for more than
      50 Myr.

PMID- 15843600
TI  - Malaria parasites are rapidly killed by dantrolene derivatives specific for the
      plasmodial surface anion channel.
AB  - Dantrolene was recently identified as a novel inhibitor of the plasmodial surface
      anion channel (PSAC), an unusual ion channel on Plasmodium falciparum-infected
      human red blood cells. Because dantrolene is used clinically, has a high
      therapeutic index, and has desirable chemical synthetic properties, it may be a
      lead compound for antimalarial development. However, dantrolene derivatives would
      need to preferentially interact with PSAC over the sarcoplasmic reticulum (SR)
      Ca2+ release channel to avoid unwanted side effects from antimalarial therapy.
      Furthermore, dantrolene's modest affinity for PSAC (K(m) of 1.2 microM) requires
      improvement. In this study, we tested 164 derivatives of dantrolene to examine
      whether these hurdles can be surmounted. A simple screen for PSAC block defined
      the minimal scaffold needed and identified compounds with > or =5-fold higher
      affinity. Single-channel patch-clamp recordings on infected human red blood cells
      with two derivatives also revealed increased blocking affinity that resulted from
      slower unbinding from a site on the extracellular face of PSAC. We tested these
      derivatives in a frog skeletal muscle contractility assay and found that, in
      contrast to dantrolene, they had little or no effect on SR Ca2+ release. Finally,
      these blockers kill in vitro parasite cultures at lower concentrations than
      dantrolene, consistent with an essential role for PSAC. Because, as a class,
      these derivatives fulfil the requirements for drug leads and can be studied with
      simple screening technology, more extensive medicinal chemistry is warranted to
      explore antimalarial development.

PMID- 15843602
TI  - Gonadal steroid attenuation of developing hamster facial motoneuron loss by
      axotomy: equal efficacy of testosterone, dihydrotestosterone, and 17-beta
      estradiol.
AB  - In the hamster facial nerve injury paradigm, we have established that androgens
      enhance both functional recovery from facial nerve paralysis and the rate of
      regeneration in the adult, through intrinsic effects on the nerve cell body
      response to injury and via an androgen receptor (AR)-mediated mechanism. Whether
      these therapeutic effects of gonadal steroids encompass neuroprotection from
      axotomy-induced cell death is the focus of the present study. Virtually 100% of
      adult hamster facial motoneurons (FMNs) survive axotomy at the stylomastoid
      foramen (SMF), whereas, before postnatal day 15 (P15), developing FMNs undergo
      substantial axotomy-induced cell death. The first part of the present study
      focuses on determining when ARs are first expressed in developing hamster FMNs.
      Using AR immunocytochemistry, it was found that males express ARs by P2 and
      females by P4, which is the earliest demonstration of AR expression in mammalian
      motoneurons reported thus far in the literature. The second half examines the
      neuroprotective effects of testosterone propionate, 17-beta estradiol, and
      dihydrotestosterone on FMNs of P7 hamsters after facial nerve transection at the
      SMF. The results demonstrate that androgens and estrogens are equally able to
      rescue approximately 20% of FMNs from axotomy-induced cell death, with the
      effects permanent. This study is the first to investigate the effects of both
      androgens and estrogens on axotomy-induced cell death in one system and, with our
      previously published work, to validate the hamster FMN injury paradigm as a model
      of choice in the investigation of both neurotherapeutic and neuroprotective
      actions of gonadal steroids.

PMID- 15843601
TI  - The chemokine stromal cell-derived factor-1 regulates the migration of sensory
      neuron progenitors.
AB  - Chemokines and their receptors are essential for the development and organization
      of the hematopoietic/lymphopoietic system and have now been shown to be expressed
      by different types of cells in the nervous system. In mouse embryos, we observed
      expression of the chemokine (CXC motif) receptor 4 (CXCR4) by neural crest cells
      migrating from the dorsal neural tube and in the dorsal root ganglia (DRGs).
      Stromal cell-derived factor-1 (SDF-1), the unique agonist for CXCR4, was
      expressed along the path taken by crest cells to the DRGs, suggesting that SDF
      1/CXCR4 signaling is needed for their migration. CXCR4 null mice exhibited small
      and malformed DRGs. Delayed migration to the DRGs was suggested by ectopic cells
      expressing tyrosine receptor kinase A (TrkA) and TrkC, neurotrophin receptors
      required by DRG sensory neuron development. In vitro, the CXCR4 chemokine
      receptor was upregulated by migratory progenitor cells just as they exited mouse
      neural tube explants, and SDF-1 acted as a chemoattractant for these cells. Most
      CXCR4-expressing progenitors differentiated to form sensory neurons with the
      properties of polymodal nociceptors. Furthermore, DRGs contained a population of
      progenitor cells that expressed CXCR4 receptors in vitro and differentiated into
      neurons with a similar phenotype. Our findings indicate an important role for SDF
      1/CXCR4 signaling in directing the migration of sensory neuron progenitors to the
      DRG and potentially in other aspects of development once the DRGs have coalesced.

PMID- 15843603
TI  - Early and rapid targeting of eye-specific axonal projections to the dorsal
      lateral geniculate nucleus in the fetal macaque.
AB  - The emergence of eye-specific axonal projections to the dorsal lateral geniculate
      nucleus (dLGN) is a well established model system for exploring the mechanisms
      underlying afferent targeting during development. Using modern tract tracing
      methods, we examined the development of this feature in the macaque, an Old World
      Primate with a visual system similar to that of humans. Cholera toxin beta
      fragment conjugated to Alexa 488 was injected into the vitreous of one eye, and
      CTbeta conjugated to Alexa 594 into the other eye of embryos at known gestational
      ages. On embryonic day 69 (E69), which is approximately 100 d before birth,
      inputs from the two eyes were extensively intermingled in the dLGN. However, even
      at this early age, portions of the dLGN were preferentially innervated by the
      right or left eye, and segregation is complete within the dorsalmost layers 5 and
      6. By E78, eye-specific segregation is clearly established throughout the
      parvocellular division of the dLGN, and substantial ocular segregation is present
      in the magnocellular division. By E84, segregation of left and right eye axons is
      essentially complete, and the six eye-specific domains that characterize the
      mature macaque dLGN are clearly discernable. These findings reveal that targeting
      of eye-specific axonal projections in the macaque occurs much earlier and more
      rapidly than previously reported. This segregation process is completed before
      the reported onset of ganglion cell axon loss and retino-dLGN synapse
      elimination, suggesting that, in the primate, eye-specific targeting occurs
      independent of traditional forms of synaptic plasticity.

PMID- 15843604
TI  - Adaptation to visuomotor rotations remaps movement vectors, not final positions.
AB  - When exposed to novel visuomotor rotations, subjects readily adapt reaching
      movements, such that the virtual display of the hand is brought to the target.
      Whereas this clearly reflects remapping of the relationship between hand
      movements and the visual display, the nature of this remapping is not well
      understood. We now examine whether such adaptation results in remapping of the
      position of the visually displayed target and the final limb position or between
      the target vector and the movement vector. The latter is defined relative to a
      starting position, whereas the former should be independent of the starting
      position. Subjects first adapted to a 30 degrees rotation during reaching
      movements made from a single starting location to four different target
      locations. After adaptation, generalization trials were introduced, during which
      reaching movements were made under the same visual rotation condition but started
      from one of two locations outside the practiced workspace. These trials were
      directed to either the previously practiced targets or new targets that reflected
      the direction and distance of the practiced trials. Generalization was greatest
      for movements made in similar directions, regardless of changes in spatial
      location. Most significantly, when reaching to the previously adapted targets,
      subjects did not reach to the previously learned limb positions but rather to
      positions that reflected a near 30 degrees rotation of the new target vector.
      These results indicate that learned visuomotor rotations remap the
      representations of movement vectors and not final positions of the limb in the
      workspace.

PMID- 15843605
TI  - Presynaptically silent GABA synapses in hippocampus.
AB  - Mammalian central synapses commonly specialize in one fast neurotransmitter,
      matching the content of their presynaptic vesicles with the appropriate receptors
      in their postsynaptic membrane. Here, I show that hippocampal cultures contain
      autaptic glutamatergic synapses that contravene this rule: in addition to
      postsynaptic glutamate receptors, they also express clusters of functional
      postsynaptic GABA(A) receptors yet lack presynaptic GABA. Hence, these synapses
      are presynaptically silent with respect to GABA. They can be unsilenced by
      loading GABA into presynaptic vesicles by endocytosis, after which a postload
      IPSC appears. This IPSC is similar to native IPSCs recorded from GABAergic
      interneurons in the same cultures. Thus, these "mistargeted" GABA(A) receptors,
      which apparently lack a signal that confers synaptic specificity, function almost
      normally. After GABA loading, glutamatergic miniature postsynaptic currents
      acquire a slow tail that is mediated by GABA(A) receptors, showing that synaptic
      vesicles can accommodate both the usual concentration of native glutamate and a
      saturating concentration of loaded GABA. After brief Ca(2+)-dependent exocytosis,
      endocytosis of GABA can proceed in low-Ca(2+) external solution. The amplitude of
      the postload IPSC declines exponentially with repetitive stimulation as the
      endocytosed GABA passes through the presynaptic vesicle cycle and is depleted.
      Hence, by using GABA as an exogenous but physiological tracer, the properties of
      these presynaptically silent synapses can provide novel insights into the content
      and cycling of vesicles in presynaptic terminals.

PMID- 15843606
TI  - Diminished neuronal activity increases neuron-neuron connectivity underlying
      silent synapse formation and the rapid conversion of silent to functional
      synapses.
AB  - Neuronal activity regulates the synaptic strength of neuronal networks. However,
      it is still unclear how diminished activity changes connection patterns in
      neuronal circuits. To address this issue, we analyzed neuronal connectivity and
      relevant mechanisms using hippocampal cultures in which developmental
      synaptogenesis had occurred. We show that diminution of network activity in
      mature neuronal circuit promotes reorganization of neuronal circuits via NR2B
      subunit-containing NMDA-type glutamate receptors (NR2B-NMDARs), which mediate
      silent synapse formation. Simultaneous double whole-cell recordings revealed that
      diminishing neuronal circuit activity for 48 h increased the number of
      synaptically connected neuron pairs with both silent and functional synapses.
      This increase was accompanied by the specific expression of NR2B-NMDARs at
      synaptic sites. Analysis of miniature EPSCs (mEPSCs) showed that the frequency of
      NMDAR-mediated, but not AMPAR-mediated, mEPSCs increased, indicating that
      diminished neuronal activity promotes silent synapse formation via the surface
      delivering NR2B-NMDARs in mature neurons. After activation of neuronal circuit by
      releasing from TTX blockade (referred as circuit reactivation), the frequency of
      AMPAR-mediated mEPSCs increased instead, and this increase was prevented by
      ifenprodil. The circuit reactivation also caused an increased colocalization of
      glutamate receptor 1-specfic and synaptic NR2B-specific puncta. These results
      indicate that the circuit reactivation converts rapidly silent synapses formed
      during activity suppression to functional synapses. These data may provide a new
      example of homeostatic circuit plasticity that entails the modulation of neuron
      neuron connectivity by synaptic activity.

PMID- 15843607
TI  - Nociceptor and hair cell transducer properties of TRPA1, a channel for pain and
      hearing.
AB  - Mechanosensory channels of sensory cells mediate the sensations of hearing,
      touch, and some forms of pain. The TRPA1 (a member of the TRP family of ion
      channel proteins) channel is activated by pain-producing chemicals, and its
      inhibition impairs hair cell mechanotransduction. As shown here and previously,
      TRPA1 is expressed by hair cells as well as by most nociceptors (small neurons of
      dorsal root, trigeminal, and nodose ganglia) and localizes to their sensory
      terminals (mechanosensory stereocilia and peripheral free nerves, respectively).
      Thus, TRPA1 channels are proposed to mediate transduction in both hair cells and
      nociceptors. Accordingly, we find that heterologously expressed TRPA1 display
      channel behaviors expected for both auditory and nociceptive transducers. First,
      TRPA1 and the hair cell transducer share a unique set of pore properties not
      described for any other channel (block by gadolinium, amiloride, gentamicin, and
      ruthenium red, a ranging conductance of approximately 100 pS that is reduced to
      54% by calcium, permeating calcium-induced potentiation followed by closure, and
      reopening by depolarization), supporting a direct role of TRPA1 as a pore-forming
      subunit of the hair cell transducer. Second, TRPA1 channels inactivate in
      hyperpolarized cells but remain open in depolarized cells. This property provides
      a mechanism for the lack of desensitization, coincidence detection, and allodynia
      that characterize pain by allowing a sensory neuron to respond constantly to
      sustained stimulation that is suprathreshold (i.e., noxious) and yet permitting
      the same cell to ignore sustained stimulation that is subthreshold (i.e.,
      innocuous). Our results support a TRPA1 role in both nociceptor and hair cell
      transduction.

PMID- 15843608
TI  - Group III metabotropic glutamate receptors and exocytosed protons inhibit L-type
      calcium currents in cones but not in rods.
AB  - Light responses of photoreceptors (rods and cones) are transmitted to the second
      order neurons (bipolar cells and horizontal cells) via glutamatergic synapses
      located in the outer plexiform layer of the retina. Although it has been well
      established that postsynaptic group III metabotropic glutamate receptors (mGluRs)
      of ON bipolar cells contribute to generating the ON signal, presynaptic roles of
      group III mGluRs remain to be elucidated at this synaptic connection. We
      addressed this issue by applying the slice patch-clamp technique to the newt
      retina. OFF bipolar cells and horizontal cells generate a steady inward current
      in the dark and a transient inward current at light offset, both of which are
      mediated via postsynaptic non-NMDA receptors. A group III mGluR-specific agonist,
      L-2-amino-4-phosphonobutyric acid (L-AP-4), inhibited both the steady and off
      transient inward currents but did not affect the glutamate-induced current in
      these postsynaptic neurons. L-AP-4 inhibited the presynaptic L-type calcium
      current (ICa) in cones by shifting the voltage dependence of activation to more
      positive membrane potentials. The inhibition of ICa was most prominent around the
      physiological range of cone membrane potentials. In contrast, L-AP-4 did not
      affect L-type ICa in rods. Paired recordings from photoreceptors and the
      synaptically connected second-order neurons confirmed that L-AP-4 inhibited both
      ICa and glutamate release in cones but not in rods. Furthermore, we found that
      exocytosed protons also inhibited ICa in cones but not in rods. Selective
      modulation of ICa in cones may help broaden the dynamic range of synaptic
      transfer by controlling the amount of transmitter release from cones.

PMID- 15843609
TI  - Role of glucocorticoids and cAMP-mediated repression in limiting corticotropin
      releasing hormone transcription during stress.
AB  - The role of glucocorticoids and the repressor isoform of cAMP response element
      (CRE) modulator (CREM), inducible cAMP early repressor (ICER), in limiting
      corticotropin-releasing hormone (CRH) transcription during restraint stress were
      examined in both intact and adrenalectomized rats receiving glucocorticoid
      replacement. CRH primary transcript, measured by intronic in situ hybridization,
      increased after 30 min of restraint and returned to basal levels by 90 min,
      despite the persistent stressor. The decline was independent of circulating
      glucocorticoids, because adrenalectomized rats displayed an identical pattern.
      ICER mRNA in the hypothalamic paraventricular nucleus (PVN) increased after 30
      min and remained elevated for up to 4 h in a glucocorticoid-independent manner.
      Western blot and electrophoretic mobility shift assay analyses showed increases
      in endogenous ICER in the PVN of rats subjected to restraint stress for 3 h.
      Chromatin immunoprecipitation assays showed the recruitment of CREM by the CRH
      CRE in conjunction with decreases in RNA polymerase II (Pol II) binding in the
      PVN region of rats restrained for 3 h. These data show that stress-induced
      glucocorticoids do not mediate the limitation of CRH transcription. Furthermore,
      the ability of CREM to bind the CRH CRE and the time relationship between
      elevated CREM and reduced Pol II recruitment by the CRH promoter suggest that
      inhibitory isoforms of CREM induced during stress contribute to the decline in
      CRH gene transcription during persistent stimulation.

PMID- 15843610
TI  - Thrombin-induced oxidative stress contributes to the death of hippocampal neurons
      in vivo: role of microglial NADPH oxidase.
AB  - The present study investigated whether thrombin, a potent microglial activator,
      can induce reactive oxygen species (ROS) generation through activation of
      microglial NADPH oxidase and if this may contribute to oxidative damage and
      consequent neurodegeneration. Seven days after intrahippocampal injection of
      thrombin, Nissl staining and immunohistochemistry using the neuronal-specific
      nuclear protein NeuN revealed a significant loss in hippocampal CA1 neurons. In
      parallel, thrombin-activated microglia, assessed by OX-42 and OX-6
      immunohistochemistry, and ROS production, assessed by hydroethidine
      histochemistry, were observed in the hippocampal CA1 area in which degeneration
      of hippocampal neurons occurred. Reverse transcription-PCR at various time points
      after thrombin administration demonstrated an early and transient expression of
      inducible nitric oxide synthase (iNOS) and several proinflammatory cytokines.
      Western blot analysis and double-label immunohistochemistry showed an increase in
      the expression of and the localization of iNOS within microglia. Additional
      studies demonstrated that thrombin induced the upregulation of membrane
      (gp91(phox)) and cytosolic (p47(phox) and p67(phox)) components, translocation of
      cytosolic proteins (p47(phox), p67(phox), and Rac1) to the membrane, and
      p67(phox) expression of the NADPH oxidase in microglia in the hippocampus in
      vivo, indicating the activation of NADPH oxidase. The thrombin-induced oxidation
      of proteins and loss of hippocampal CA1 neurons were partially inhibited by an
      NADPH oxidase inhibitor and by an antioxidant. To our knowledge, the present
      study is the first to demonstrate that thrombin-induced neurotoxicity in the
      hippocampus in vivo is caused by microglial NADPH oxidase-mediated oxidative
      stress. This suggests that thrombin inhibition or enhancing antioxidants may be
      beneficial for the treatment of neurodegenerative diseases, such as Alzheimer's
      disease, that are associated with microglial-derived oxidative damage.

PMID- 15843611
TI  - Selective glial cell line-derived neurotrophic factor production in adult
      dopaminergic carotid body cells in situ and after intrastriatal transplantation.
AB  - Glial cell line-derived neurotrophic factor (GDNF) exerts a notable protective
      effect on dopaminergic neurons in rodent and primate models of Parkinson's
      disease (PD). The clinical applicability of this therapy is, however, hampered by
      the need of a durable and stable GDNF source allowing the safe and continuous
      delivery of the trophic factor into the brain parenchyma. Intrastriatal carotid
      body (CB) autografting is a neuroprotective therapy potentially useful in PD. It
      induces long-term recovery of parkinsonian animals through a trophic effect on
      nigrostriatal neurons and causes amelioration of symptoms in some PD patients.
      Moreover, the adult rodent CB has been shown to express GDNF. Here we show, using
      heterozygous GDNF/lacZ knock-out mice, that unexpectedly CB dopaminergic glomus,
      or type I, cells are the source of CB GDNF. Among the neural or paraneural cells
      tested, glomus cells are those that synthesize and release the highest amount of
      GDNF in the adult rodent (as measured by standard and in situ ELISA).
      Furthermore, GDNF expression by glomus cells is maintained after intrastriatal
      grafting and in CB of aged and parkinsonian 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-treated animals. Thus, glomus cells appear to be prototypical
      abundant sources of GDNF, ideally suited to be used as biological pumps for the
      endogenous delivery of trophic factors in PD and other neurodegenerative
      diseases.

PMID- 15843612
TI  - Brain-specific knock-out of hypoxia-inducible factor-1alpha reduces rather than
      increases hypoxic-ischemic damage.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) plays an essential role in cellular
      and systemic O(2) homeostasis by regulating the expression of genes important in
      glycolysis, erythropoiesis, angiogenesis, and catecholamine metabolism. It is
      also believed to be a key component of the cellular response to hypoxia and
      ischemia under pathophysiological conditions, such as stroke. To clarify the
      function of HIF-1alpha in the brain, we exposed adult mice with late-stage brain
      deletion of HIF-1alpha to hypoxic injuries. Contrary to expectations, the brains
      from the HIF-1alpha-deficient mice were protected from hypoxia-induced cell
      death. These surprising findings suggest that decreasing the level of HIF-1alpha
      can be neuroprotective. Gene chip expression analysis revealed that, contrary to
      expectations, the majority of hypoxia-dependent gene-expression changes were
      unaltered, whereas a specific downregulation of apoptotic genes was observed in
      the HIF-1alpha-deficient mice. Although the role of HIF-1alpha has been
      extensively characterized in vitro, in cancer models, and in chronic
      preconditioning paradigms, this is the first study to evaluate the role of HIF
      1alpha in vivo in the brain in response to acute hypoxia/ischemia. Our data
      suggest, that in acute hypoxia, the neuroprotection found in the HIF-1alpha
      deficient mice is mechanistically consistent with a predominant role of HIF
      1alpha as proapoptotic and loss of function leads to neuroprotection.
      Furthermore, our data suggest that functional redundancy develops after excluding
      HIF-1alpha, leading to the preservation of gene expression regulating the
      majority of other previously characterized HIF-dependent genes.

PMID- 15843613
TI  - Proton-mediated feedback inhibition of presynaptic calcium channels at the cone
      photoreceptor synapse.
AB  - Generation of center-surround antagonistic receptive fields in the outer retina
      occurs via inhibitory feedback modulation of presynaptic voltage-gated calcium
      channels in cone photoreceptor synaptic terminals. Both conventional and
      unconventional neurotransmitters, as well as an ephaptic effect, have been
      proposed, but the intercellular messaging that mediates the inhibitory feedback
      signal from postsynaptic horizontal cells (HCs) to cones remains unknown. We
      examined the possibility that proton concentration in the synaptic cleft is
      regulated by HCs and that it carries the feedback signal to cones. In isolated,
      dark-adapted goldfish retina, we assessed feedback in the responses of HCs to
      light and found that strengthened pH buffering reduced both rollback and the
      depolarization to red light. In zebrafish retinal slices loaded with Fluo-4,
      depolarization with elevated K(+) increased Ca signals in the synaptic terminals
      of cone photoreceptors. Kainic acid, which depolarizes HCs but has no direct
      effect on cones, depressed the K(+)-induced Ca signal, whereas CNQX, which
      hyperpolarizes HCs, increased the Ca signals, suggesting that polarization of HCs
      alters inhibitory feedback to cones. We found that these feedback signals were
      blocked by elevated extracellular pH buffering, as well as amiloride and divalent
      cations. Voltage clamp of isolated HCs revealed an amiloride-sensitive
      conductance that could mediate modulation of cleft pH dependent on the membrane
      potential of these postsynaptic cells.

PMID- 15843614
TI  - Calcium-stimulated adenylyl cyclases are critical modulators of neuronal ethanol
      sensitivity.
AB  - The importance of the cAMP signaling pathway in the modulation of ethanol
      sensitivity has been suggested by studies in organisms from Drosophila
      melanogaster to man. However, the involvement of specific isoforms of adenylyl
      cyclase (AC), the molecule that converts ATP to cAMP, has not been systemically
      determined in vivo. Because AC1 and AC8 are the only AC isoforms stimulated by
      calcium, and ethanol modulates calcium flux by the NMDA receptor, we hypothesized
      that these ACs would be important in the neural response to ethanol. AC1 knock
      out (KO) mice and double knock-out (DKO) mice with genetic deletion of both AC1
      and AC8 display substantially increased sensitivity to ethanol-induced sedation
      compared with wild-type (WT) mice, whereas AC8 KO mice are only minimally more
      sensitive. In contrast, AC8 KO and DKO mice, but not AC1 KO mice, demonstrate
      decreased voluntary ethanol consumption compared with WT mice. DKO mice do not
      display increased sleep time compared with WT mice after administration of
      ketamine or pentobarbital, indicating that the mechanism of enhanced ethanol
      sensitivity in these mice is likely distinct from the antagonism of ethanol of
      the NMDA receptor and potentiation of the GABA(A) receptor. Ethanol does not
      enhance calcium-stimulated AC activity, but the ethanol-induced phosphorylation
      of a discrete subset of protein kinase A (PKA) substrates is compromised in the
      brains of DKO mice. These results indicate that the unique activation of PKA
      signaling mediated by the calcium-stimulated ACs is an important component of the
      neuronal response to ethanol.

PMID- 15843615
TI  - The wake-promoting hypocretin/orexin neurons change their response to
      noradrenaline after sleep deprivation.
AB  - Sleep deprivation is accompanied by the progressive development of an
      irresistible need to sleep, a phenomenon whose mechanism has remained elusive.
      Here, we identified for the first time a reflection of that phenomenon in vitro
      by showing that, after a short 2 h period of total sleep deprivation, the action
      of noradrenaline on the wake-promoting hypocretin/orexin neurons changes from an
      excitation to an inhibition. We propose that such a conspicuous modification of
      responsiveness should contribute to the growing sleepiness that accompanies sleep
      deprivation.

PMID- 15843616
TI  - Developmental transformation of the release modality at the calyx of Held
      synapse.
AB  - Ca(2+) influx through voltage-gated Ca(2+) channels (VGCCs) into nerve terminals
      triggers vesicular fusion and neurotransmitter release. However, it is unknown
      whether the coupling between VGCCs and synaptic vesicles (SVs) is developmentally
      regulated. By paired patch-clamp recordings from the mouse calyx of Held synapse,
      we show here that injection of a Ca(2+) buffer with slow binding kinetics (EGTA;
      10 mm) potently attenuated transmitter release in young terminals [postnatal day
      8 (P8)-P12] but produced little effect in older ones (P16-P18), suggesting that
      SVs in young synapses are loosely coupled to VGCCs, but the coupling tightens
      spatially during maturation. Using voltage paradigms that specifically recruit
      different numbers of VGCCs without changing the driving force for Ca(2+), we
      found that the Ca(2+) cooperativity (m), estimated from graded presynaptic Ca(2+)
      currents and transmitter release, was much higher in P8-P12 synapses (m = 4.8
      5.5) than that in P16-P18 synapses (m = 2.8-3.0; 1 mm [Ca(2+)](o)), implying that
      the number of VGCCs or Ca(2+) domains required for release of single SVs
      decreases with maturation. The m value remained significantly different between
      two age groups at 35 degrees C or in 2 mm [Ca(2+)](o) and was independent of
      postsynaptic receptor desensitization. We demonstrated that release from P8-P12
      terminals involved both N- and P/Q-type VGCCs, but P/Q-type-associated release
      sites specifically displayed low m values. These results suggest a developmental
      transformation of the release modality from "microdomain," involving cooperative
      action of many loosely coupled N- and P/Q-type VGCCs, to "nanodomain," in which
      opening of fewer tightly coupled P/Q-type VGCCs effectively induce a fusion
      event. Spatial tightening improves the release efficiency and is likely a
      critical step for the development of high-fidelity neurotransmission in this and
      other central synapses.

PMID- 15843617
TI  - Potassium channel blockers inhibit the triggers of attacks in the calcium channel
      mouse mutant tottering.
AB  - Humans with the disorder episodic ataxia type 2 (EA2) and the tottering mouse
      mutant exhibit episodic attacks induced by emotional and chemical stress. Both
      the human and mouse disorders result from mutations in CACNA1A, the gene encoding
      the alpha(1)2.1 subunit of Ca(v)2.1 voltage-gated calcium channels. These
      mutations predict reduced calcium currents, particularly in cerebellar Purkinje
      cells, where these channels are most abundant. 4-Aminopyridine (4-AP), a
      nonselective blocker of K(v) voltage-gated potassium channels, alleviates attacks
      of ataxia in EA2 patients. To test the specificity of the effect for K(v)
      channels, aminopyridine analogs were assessed for their ability to ameliorate
      attacks of dyskinesia in tottering mice. 4-AP and 3,4-diaminopyridine (3,4-DiAP),
      which have relatively high affinities for K(v) channels, reduced the frequency of
      restraint- and caffeine-induced attacks. Furthermore, microinjection of 3,4-DiAP
      into the cerebellum completely blocked attacks in tottering mice. Other
      aminopyridine analogs reduced attack frequency but, consistent with their lower
      affinities for K(v) channels, required comparatively higher doses. These results
      suggest that aminopyridines block tottering mouse attacks via cerebellar K(v)
      channels. That both stress- and caffeine-induced attacks were blocked by
      aminopyridines suggests that these triggers act via similar mechanisms. Although
      4-AP and 3,4-DiAP were effective in preventing attacks in tottering mice, these
      compounds did not affect the severity of "breakthrough" attacks that occurred in
      the presence of a drug. These results suggest that the aminopyridines increase
      the threshold for attack initiation without mitigating the character of the
      attack, indicating that attack initiation is mediated by mechanisms that are
      independent of the neurological phenotype.

PMID- 15843618
TI  - Abnormal cortical complexity and thickness profiles mapped in Williams syndrome.
AB  - We identified and mapped an anatomically localized failure of cortical maturation
      in Williams syndrome (WS), a genetic condition associated with deletion of
      approximately 20 contiguous genes on chromosome 7. Detailed three-dimensional
      (3D) maps of cortical thickness, based on magnetic resonance imaging (MRI) scans
      of 164 brain hemispheres, identified a delimited zone of right hemisphere
      perisylvian cortex that was thicker in WS than in matched controls, despite
      pervasive gray and white matter deficits and reduced total cerebral volumes. 3D
      cortical surface models were extracted from 82 T1-weighted brain MRI scans (256 x
      192 x 124 volumes) of 42 subjects with genetically confirmed WS (mean +/- SD,
      29.2 +/- 9.0 years of age; 19 males, 23 females) and 40 age-matched healthy
      controls (27.5 +/- 7.4 years of age; 16 males, 24 females). A cortical pattern
      matching technique used 72 sulcal landmarks traced on each brain as anchors to
      align cortical thickness maps across subjects, build group average maps, and
      identify regions with altered cortical thickness in WS. Cortical models were
      remeshed in frequency space to compute their fractal dimension (surface
      complexity) for each hemisphere and lobe. Surface complexity was significantly
      increased in WS (p < 0.0015 and p < 0.0014 for left and right hemispheres,
      respectively) and correlated with temporoparietal gyrification differences,
      classified via Steinmetz criteria. In WS, cortical thickness was increased by 5
      10% in a circumscribed right hemisphere perisylvian and inferior temporal zone (p
      < 0.002). Spatially extended cortical regions were identified with increased
      complexity and thickness; cortical thickness and complexity were also positively
      correlated in controls (p < 0.03). These findings visualize cortical zones with
      altered anatomy in WS, which merit additional study with techniques to assess
      function and connectivity.

PMID- 15843619
TI  - Neurotoxic calcium transfer from endoplasmic reticulum to mitochondria is
      regulated by cyclin-dependent kinase 5-dependent phosphorylation of tau.
AB  - Increased levels of mitochondrial-free calcium have been associated with several
      cell-death paradigms, such as excitotoxicity and ceramide-mediated neuronal
      death. In the latter, calcium is transferred from the endoplasmic reticulum to
      mitochondria by a mechanism that is only partly understood. We show here that
      CDK5 (cyclin-dependent kinase 5) plays a role. Free calcium levels in the
      endoplasmic reticulum and mitochondria were measured with fluorescent markers in
      C2-ceramide-treated primary cultures of mesencephalic neurons and differentiated
      pheochromocytoma PC12 cells. Calcium levels decreased in the endoplasmic
      reticulum as they increased in mitochondria. Both changes were blocked by the
      pharmacological and molecular CDK5 inhibitors roscovitine and a dominant-negative
      form of CDK5. Although the kinase did not mediate the transfer of calcium per se,
      which required the proapoptotic Bcl-2 family protein t-Bid (the truncated form of
      Bid), it facilitated the transfer by inducing the clustering of endoplasmic
      reticulum and mitochondria around the centrosome where they formed close
      contacts, as shown by immunocytochemistry and electron microscopy. Organelle
      clustering resulted from CDK5-dependent phosphorylation of the microtubule
      associated protein tau on threonine 231. This caused its release from
      microtubules into the soluble fraction of cellular proteins, which appears to
      favor retrograde transport of the organelles. Mutation of threonine 231 to
      alanine, so that tau could not be phosphorylated at this site, prevented the
      ceramide-induced release of tau from microtubules, organelle clustering, the
      increase in mitochondrial-free calcium levels, and neuronal death, demonstrating
      the importance of the CDK5-dependent signaling cascade in this calcium-dependent
      cell-death mechanism.

PMID- 15843620
TI  - Cognitive dysfunction precedes neuropathology and motor abnormalities in the
      YAC128 mouse model of Huntington's disease.
AB  - Huntington's disease (HD) is an adult-onset neurodegenerative disorder involving
      motor dysfunction, cognitive deficits, and psychiatric disturbances that result
      from underlying striatal and cortical dysfunction and neuropathology. The YAC128
      mouse model of HD reproduces both the motor deficits and selective degeneration
      observed in the human disease. However, the presence of cognitive impairment in
      this model has not been determined. Here, we report mild cognitive deficits in
      YAC128 mice that precede motor onset and progressively worsen with age. Rotarod
      testing revealed a motor learning deficit at 2 months of age that progresses such
      that by 12 months of age, untrained YAC128 mice are unable to learn the rotarod
      task. Additional support for cognitive dysfunction is evident in a simple
      swimming test in which YAC128 mice take longer to find the platform than wild
      type (WT) controls beginning at 8 months of age. YAC128 mice also have deficits
      in open-field habituation and in a swimming T-maze test at this age. Strikingly,
      in the reversal phase of the swimming T-maze test, YAC128 mice take twice as long
      as WT mice to locate the platform, indicating a difficulty in changing strategy.
      At 12 months of age, YAC128 mice show decreased prepulse inhibition and
      habituation to acoustic startle. The clear pattern of cognitive dysfunction in
      YAC128 mice is similar to the symptoms and progression of cognitive deficits in
      human HD and provides both the opportunity to examine the relationship between
      cognitive dysfunction, motor impairment, and neuropathology in HD and to assess
      whether potential therapies for HD can restore cognitive function.

PMID- 15843621
TI  - Use of laser-capture microdissection for the identification of marker genes for
      the ventromedial hypothalamic nucleus.
AB  - The ventromedial hypothalamic nucleus (VMH) plays an important role in the
      control of feeding and energy homeostasis. In contrast to other hypothalamic
      nuclei that are also known to regulate energy balance, there is a paucity of
      nucleus-specific marker genes for the VMH, limiting the application of molecular
      approaches for analyzing VMH information processing, function, and circuitry.
      Here, we report the use of laser-capture microdissection to isolate a set of
      cDNAs that are enriched in the VMH relative to two adjacent hypothalamic nuclei,
      the arcuate and dorsomedial hypothalamus. The relative expression levels of nine
      of the 12 most robustly expressed VMH-enriched genes were confirmed by real-time
      PCR analysis using separate RNAs from these three nuclei. Three of these VMH
      enriched genes were further characterized by in situ hybridization
      histochemistry, including pituitary adenylate cyclase activating polypeptide,
      cerebellin 1, and an expressed sequence tag named LBH2. Finally, to test whether
      some of these genes were coordinately regulated, we monitored their expression in
      steroidogenic factor 1 (SF-1) knock-out mice. SF-1 is a transcription factor that
      controls the development of the VMH. The RNA levels for four of these genes were
      reduced in these knock-out animals, further suggesting that they are direct or
      indirect targets of this orphan nuclear receptor. The VMH-enriched genes
      identified here provide a basis for a functional analysis of VMH neuronal
      subpopulations via the use of bacterial artificial chromosome transgenics and
      related technologies. These results also demonstrate the utility of laser-capture
      microdissection coupled with microarray technology to identify nucleus-specific
      transcriptional networks.

PMID- 15843622
TI  - Requirement of Cul3 for axonal arborization and dendritic elaboration in
      Drosophila mushroom body neurons.
AB  - Cul3 belongs to the family of cullin proteins, which function as scaffold
      proteins of E3 ubiquitin ligase complexes. Here we show cell-autonomous
      involvement of Cul3 in axonal arborization and dendritic elaboration of
      Drosophila mushroom body neurons. Cul3 mutant neurons are defective in terminal
      morphogenesis of neurites. Interestingly, mutant axons often terminate around
      branching points. In addition, dendritic elaboration is severely affected in Cul3
      mutant neurons. However, loss of Cul3 function does not affect extension of the
      axons that rarely arborize. Function of cullin-type proteins has been shown to
      require covalent attachment of Nedd8 (neural precursor cell-expressed
      developmentally downregulated), a ubiquitin-like protein. Consistent with this
      notion, Cul3 is inactivated by a mutation in its conserved neddylation site, and
      Nedd8 mutant neurons exhibit similar neuronal morphogenetic defects. Together,
      Cul3 plays an essential role in both axonal arborization and proper elaboration
      of dendrites and may require neddylation for its proper function.

PMID- 15843623
TI  - Unilateral storage of fear memories by the amygdala.
AB  - Pavlovian fear conditioning is an associative learning task in which subjects are
      trained to respond defensively to a neutral conditioned stimulus (CS) by pairing
      it with an aversive unconditioned stimulus (US). This type of learning depends
      critically on the amygdala, and evidence suggests that synaptic plasticity within
      the lateral nucleus of the amygdala (LA) may be responsible for storing memories
      of the CS-US association. In the present study, we trained rats to fear an
      auditory CS by pairing it with a shock US delivered to one eyelid. Conditioning
      was assessed by measuring freezing responses evoked by the CS during a subsequent
      test session. The amygdala was unilaterally inactivated during either the
      training or the testing session by intracranial infusions of muscimol into the
      LA. We found that both acquisition and expression of conditioned freezing to the
      CS depended on the amygdala contralateral but not ipsilateral from the eyelid
      where the shock US was delivered. To explain this surprising result, we propose
      that the shock US is relayed from the eyelid to the amygdala via lateralized
      nociceptive sensory pathways, which causes memories of the CS-US association to
      be stored by the amygdala contralateral but not ipsilateral from the shocked
      eyelid. Our results demonstrate that the fear-learning circuitry of the amygdala
      is functionally lateralized according to the anatomical source of predicted
      threats. In future studies, the cellular mechanisms of emotional memory storage
      might be pinpointed by identifying cellular processes that occur only in the
      amygdala contralateral but not ipsilateral from the US during lateralized fear
      conditioning.

PMID- 15843627
TI  - Layer 6 cortico-thalamic pyramidal cells preferentially innervate interneurons
      and generate facilitating EPSPs.
AB  - The properties of the connections made by the axons of pyramidal cells with
      cortico-thalamic (CT)-like morphology with a range of postsynaptic layer 6
      targets were studied with dual intracellular recordings in slices of adult rat
      and cat neocortex. The cells were filled with biocytin and identified
      morphologically and, where appropriate, immunofluorescently. CT-like pyramids
      contacted interneurons with a very high probability (up to 1:2) but contacted
      other layer 6 pyramidal cells only rarely (approximately 1:80). The excitatory
      postsynaptic potentials (EPSPs) that they elicited both in pyramidal cells and in
      a variety of types of interneurons (including those immunopositive for
      parvalbumin and for somatostatin) facilitated, the second EPSP being larger than
      the first over a range of interspike intervals. Facilitation was not, however,
      maximal at the shortest intervals; in fact, depression was apparent at some
      connections at short interspike intervals. Facilitation in the majority of
      connections peaked at intervals of 25-35 ms and then declined slowly. Nor did
      these connections display the augmentation typical of many other strongly
      facilitating connections. Third EPSPs were smaller on average than second EPSPs,
      and fourth and subsequent EPSPs could be depressed (relative to first EPSPs). The
      properties of the outputs of these CT-like pyramidal cells are therefore quite
      distinct from those of other pyramidal cells, both within layer 6 and in other
      layers, possibly reflecting their unique role as both first order thalamo
      cortical recipient and cortico-thalamic output neurons.

PMID- 15843628
TI  - Synchrony dynamics in monkey V1 predict success in visual detection.
AB  - Behavioral measures such as expectancy and attention have been associated with
      the strength of synchronous neural activity. On this basis, it is hypothesized
      that synchronous activity affects our ability to detect and recognize visual
      objects. To investigate the role of synchronous activity in visual perception, we
      studied the magnitude and precision of correlated activity, before and after
      stimulus presentation within the visual cortex (V1), in relation to a monkey's
      performance in a figure-ground discrimination task. We show that during the
      period of stimulus presentation a transition in synchronized activity occurs that
      is characterized by a reduction of the correlation peak height and width. Before
      stimulus onset, broad peak correlations are observed that change towards thin
      peak correlations after stimulus onset, due to a specific decrease of low
      frequency components. The magnitude of the transition in correlated activity is
      larger, i.e. a stronger desynchronization occurs, when the animal perceives the
      stimulus correctly than when the animal fails to detect the stimulus. These
      results therefore show that a transition in synchronous firing is important for
      the detection of sensory stimuli. We hypothesize that the transition in synchrony
      reflects a change from loose and global neuronal interactions towards a finer
      temporal and spatial scale of neuronal interactions, and that such a change in
      neuronal interactions is required for figure-ground discrimination.

PMID- 15843629
TI  - Role of the protomap and target-derived signals in the development of
      intrahemispheric connections.
AB  - Mechanisms intrinsic to the early cerebral cortex have been implicated in the
      establishment of cortical area identity. However, the extent to which the
      cortical protomap contributes to the formation of highly complex intrahemispheric
      connections remains obscure. Mechanisms by which postmitotic neurons establish
      correct corticocortical connections later in corticogenesis also remain to be
      elucidated. Here, we used a new transplantation method, employing donor tissue
      harvested from enhanced green fluorescent protein-expressing rats, to show that
      cortical progenitors are regionally specified for connectional potential and that
      this controls the development of specific intrahemispheric projections. The
      acquisition of connectional capacity relies on positional cues within the
      cortical primordium, but is independent of thalamic inputs. In addition, since
      cortical neurons developing in organotypic slice culture extended axons more
      prominently into their normal cortical target tissues than into non-target
      tissues, we suggest that cortical neurons respond to specific signals derived
      from their cortical targets.

PMID- 15843630
TI  - Bursting of prefrontal cortex neurons in awake rats is regulated by metabotropic
      glutamate 5 (mGlu5) receptors: rate-dependent influence and interaction with NMDA
      receptors.
AB  - Metabotropic glutamate 5 (mGlu5) receptors have been recently implicated in
      prefrontal cortex (PFC)-dependent executive functions because inhibition of mGlu5
      receptors impairs working memory and worsens cognitive-impairing effects of NMDA
      receptor antagonists. To better understand the mechanisms by which mGlu5
      receptors influence PFC function, we examined the effects of selective mGlu5
      receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP), given alone or in
      combination with the NMDA receptor antagonist MK801, on ensemble single unit
      activity in the medial PFC (mPFC) of behaving rats. MPEP decreased the
      spontaneous burst activity of the majority of mPFC neurons. This inhibition was
      selective for the most active cells because greater decreases were observed in
      neurons with higher baseline firing rates. MPEP augmented the effects of MK801 on
      burst activity, variability of spike firing and random spike activity. These
      findings demonstrate that in awake animals mGlu5 receptors regulate the function
      of PFC neurons by two related mechanisms: (i) rate-dependent excitatory influence
      on spontaneous burst activity; and (ii) potentiation of NMDA receptor mediated
      effects on firing rate and burst activity. These mechanisms support the idea that
      modulation of mGlu5 receptors may provide a pharmacological strategy for fine
      tuning the temporal pattern of firing of PFC neurons.

PMID- 15843631
TI  - Modulation of antisaccades by transcranial magnetic stimulation of the human
      frontal eye field.
AB  - It has been suggested that the frontal eye field (FEF), which is involved with
      the inhibition and generation of saccades, is engaged to a different degree in
      pro- and antisaccades. Pro- and antisaccades are often assessed in separate
      experimental blocks. In such cases, saccade inhibition is required for
      antisaccades but not for prosaccades. To more directly assess the role of the FEF
      in saccade inhibition and generation, a new paradigm was used in which inhibition
      was necessary on pro- and antisaccade trials. Participants looked in the
      direction indicated by a target ('<' or '>') that appeared in the left or right
      visual field. When the pointing direction and the location were congruent,
      prosaccades were executed; otherwise antisaccades were required. Saccadic
      latencies were measured in blocks without and with single pulse transcranial
      magnetic stimulation (TMS) to the right FEF or a right posterior control site.
      Results showed that antisaccades generated into the hemifield ipsilateral to the
      TMS were significantly delayed after TMS over the FEF, but not the posterior
      control site. This result is interpreted in terms of a modulation of saccade
      inhibition to the contralateral visual field due to disruption of processing in
      the FEF.

PMID- 15843632
TI  - Dynamics of auditory plasticity after cochlear implantation: a longitudinal
      study.
AB  - Human representational cortex may fundamentally alter its organization and
      (re)gain the capacity for auditory processing even when it is deprived of its
      input for more than two decades. Stimulus-evoked brain activity was recorded in
      post-lingual deaf patients after implantation of a cochlear prosthesis, which
      partly restored their hearing. During a 2 year follow-up study this activity
      revealed almost normal component configuration and was localized in the auditory
      cortex, demonstrating adequacy of the cochlear implant stimulation. Evoked brain
      activity increased over several months after the cochlear implant was turned on.
      This is taken as a measure of the temporal dynamics of plasticity of the human
      auditory system after implantation of cochlear prosthesis.

PMID- 15843633
TI  - Genetic differentiation and estimation of effective population size and migration
      rates in two sympatric ecotypes of the marine snail Littorina saxatilis.
AB  - On exposed rocky shores in Galicia (northwest Spain), a striking polymorphism
      exists between two ecotypes (RB and SU) of Littorina saxatilis that occupy
      different levels of the intertidal zone and exhibit an incomplete reproductive
      isolation. The setting has been suggested to represent ongoing sympatric
      speciation by ecological adaptation of the two ecotypes to their respective
      habitats. In this article we address whether or not the ecotypes have developed
      their own population structures in response to the rigors of their corresponding
      environments and life histories. We analyzed four to five allozymic loci from
      three surveys of the same sites, spanning a 14-year period. An experimental
      design including three localities with two transects per locality and three shore
      levels allowed studying temporal and spatial population structure and estimation
      of effective population sizes (N(e)), neighborhood sizes (N(n)), and migration
      rates (m). Genetic differentiation was significantly lower in RB populations
      (theta(ST) = 0.067) than in SU ones (theta(ST) = 0.124). Mean estimates of N(e),
      N(n), and m did not differ significantly between ecotypes, but local ecotype
      differences in migration between the two closest localities (larger migration
      rates in RB than in SU populations) could explain the pattern in population
      differentiation.

PMID- 15843634
TI  - Selection bias in quantitative trait loci mapping.
AB  - A simulation study was performed to see whether selection affected quantitative
      trait loci (QTL) mapping. Populations under random selection, under selection
      among full-sib families, and under selection within a full-sib family were
      simulated each with heritability of 0.3, 0.5, and 0.7. They were analyzed with
      the marker spacing of 10 cM and 20 cM. The accuracy for QTL detection decreased
      for the populations under selection within full-sib family. Estimates of QTL
      effects and positions differed (P < .05) from their input values. The problems
      could be ignored when mapping a QTL for the populations under selection among
      full-sib families. A large heritability helped reduction of such problems. When
      the animals were selected within a full-sib family, the QTL was detected for the
      populations with heritability of 0.5 or larger using the marker spacing of 10 cM,
      and with heritability of 0.7 using the marker spacing of 20 cM. This study
      implied that when selection was introduced, the accuracy for QTL detection
      decreased and the estimates of QTL effects were biased. A caution was warranted
      on the decision of data (including selected animals to be genotyped) for QTL
      mapping.

PMID- 15843635
TI  - Multiplexed microsatellite markers for the genetic analysis of Eucalyptus
      leucoxylon (Myrtaceae) and their utility for ecological and breeding studies in
      other eucalyptus species.
AB  - Eucalyptus leucoxylon is a widespread woodland tree species found in southeastern
      Australia that has suffered from, and continues to be, threatened by the impacts
      of habitat clearance and degradation. Populations now consist predominantly of
      scattered individuals, and their conservation status is of increasing concern. We
      report the development and characterization of a set of eight highly polymorphic
      microsatellite loci for E. leucoxylon. The loci can be amplified in three PCR
      multiplexes and electrophoresed in a single lane, allowing rapid throughput of
      large numbers of samples. A total of 111 alleles were detected in 68 individuals
      with an average of 12.3 alleles per locus, a mean expected heterozygosity of
      0.83, and a mean observed heterozygosity of 0.72. The combined probabilities of
      identity and probabilities of paternity exclusion allow an extremely precise
      level of individual identification, indicating that these microsatellite markers
      will be ideal for population genetic and parentage-type studies in E. leucoxylon.
      The markers also exhibited an average of 76% conservation within the subgenus
      Symphyomyrtus, to which E. leucoxylon belongs, and 53% conservation across other
      subgenera of Eucalyptus, demonstrating the potential of these markers in
      ecological and breeding studies in a wide range of Eucalyptus species.

PMID- 15843636
TI  - Sequence variation and gene duplication at MHC DQB loci of baiji (Lipotes
      vexillifer), a Chinese river dolphin.
AB  - The major histocompatibility complex (MHC) is a fundamental part of the
      vertebrate immune system, and the high variability in many MHC genes is thought
      to play an important role in the recognition of parasites. Baiji (Lipotes
      vexillifer) is one of the most endangered species in the world. Its wild
      population has declined to fewer than 100 individuals and has a very high risk of
      becoming extinct in the near future. In this study we present a first step in the
      molecular characterization of a DQB-like locus of baiji by nucleotide sequence
      analysis of the polymorphic exon 2 segments. In the examined 172 bp sequences
      from a group of 18 incidentally captured or stranded individuals, 48 variable
      sites were determined and 43 alleles were identified, many of which were
      represented by only one clone. Three to seven alleles were found in each
      individual, suggesting gene duplications. No deletion, insertion, or exceptional
      stop codon was detected, suggesting these alleles function in vivo. Phylogenetic
      reconstruction using neighbor joining grouped the 43 alleles into two distinct
      lineages, differing by seven nucleotides and four amino acids. Substitutions of
      amino acids tend to be clustered around sites postulated to be responsible for
      selective peptide recognition. In the peptide-binding region (PBR) of the DQB
      locus, the average number of nonsynonymous substitutions per site is greater than
      that of synonymous substitutions per site (0.1962 versus 0.0256, respectively).
      Nucleotide and amino acid sequences both showed a relatively high level of
      similarity (nucleotides 90.6%; amino acids 80.6%) to those of beluga whale
      (Delphinapterus leucas) and narwhal (Monodon monoceros). The high level of baiji
      MHC polymorphism revealed in the present study has not been reported in other
      cetaceans and could be a consequence of the small baiji population adapting to
      freshwater with a relatively high level of pathogens.

PMID- 15843637
TI  - Genetic analysis of the species cytoplasm specific gene (scs d) derived from
      durum wheat.
AB  - The action of species cytoplasm specific (scs) gene(s) can be observed when a
      durum (Triticum turgidum L.) nucleus is placed in the Aegilops longissimum S. &
      M. cytoplasm. This alloplasmic combination, (lo) durum, results in nonviable
      progeny. A scs gene derived from T. timopheevii Zhuk. (scs(ti)) produced
      compatibility with the (lo) cytoplasm. The resulting hemizygous (lo) scs(ti)-
      durum line was male sterile and when crossed to normal durum produced a 1:1 ratio
      of plump, viable (PV) seeds with scs(ti) and shriveled inviable (SIV) seeds
      without scs(ti). In a systematic characterization of durum lines an unusual line
      was identified that when crossed to (lo) scs(ti)- produced all PV seeds. When
      planted these PV seeds segregated at a 1:1 ratio of normal vigor plants (NVPs)
      and low vigor plants (LVPs). The LVP senescence before full maturity. The NVPs
      were male sterile and when crossed to common durum lines resulted in all plump
      seeds that again segregated at a 1:1 ratio of NVPs to LVPs. The crosses of these
      NVPs to common durum lines resulted in a 1:1 ratio of PV to SIV seeds. This study
      was extended to 317 individuals segregating for scs(ti) and the new locus,
      derived from durum wheat (scs(d)), establishing the allelic relationship of these
      two genes.

PMID- 15843638
TI  - Persistent organic pollutants in source-separated compost and its feedstock
      materials--a review of field studies.
AB  - Composting and the application of compost to the soil follow the principle of
      recycling and sustainability. Compost can also have a positive effect on
      physical, chemical, and biological soil parameters. However, little is known
      about the origin, concentration, and transformation of persistent organic
      pollutants (POPs) in compost. We therefore compiled literature data on some
      priority POPs in compost and its main feedstock materials from more than 60
      reports. Our data evaluation suggests the following findings. First, median
      concentrations of Sigma 16 polycyclic aromatic hydrocarbons (PAHs), Sigma 6
      polychlorinated biphenyls (PCBs), and Sigma 17 polychlorinated dibenzo-p-dioxins
      and -furans (PCDD/Fs) were higher in green waste (1803, 15.6 microg/kg dry wt.,
      and 2.5 ng international toxicity equivalent [I-TEQ]/kg dry wt.) than in organic
      household waste (635, 14.6 microg/kg dry wt., and 2.2 ng I-TEQ/kg dry wt.) and
      kitchen waste (not available [NA], 14.9 microg/kg dry wt., 0.4 ng I-TEQ/kg dry
      wt.). The POP concentrations in foliage were up to 12 times higher than in other
      feedstock materials. Second, in contrast, compost from organic household waste
      and green waste contained similar amounts of Sigma 16 PAHs, Sigma 6 PCBs, and
      Sigma 17 PCDD/Fs (1915, 39.8 microg/kg dry wt., and 9.5 ng I-TEQ/kg dry wt., and
      1715, 30.6 microg/kg dry wt., and 8.5 ng I-TEQ/kg dry wt., respectively). Third,
      concentrations of three-ring PAHs were reduced during the composting process,
      whereas five- to six-ring PAHs and Sigma 6 PCBs increased by roughly a factor of
      two due to mass reduction during composting. Sigma 17 PCDD/Fs had accumulated by
      up to a factor of 14. Fourth, urban feedstock and compost had higher POP
      concentrations than rural material. Fifth, the highest concentrations of POPs
      were usually observed in summer samples. Finally, median compost concentrations
      of POPs were greater by up to one order of magnitude than in arable soils, as the
      primary recipients of compost, but were well within the range of many urban
      soils. In conclusion, this work provides a basis for the further improvement of
      composting and for future risk assessments of compost application.

PMID- 15843639
TI  - Planned versus actual outcomes as a result of animal feeding operation decisions
      for managing phosphorus.
AB  - The paper explores how decisions made on animal feeding operations (AFOs)
      influence the management of manure and phosphorus. Variability among these
      decisions from operation to operation and from field to field can influence the
      validity of nutrient loss risk assessments. These assessments are based on
      assumptions that the decision outcomes regarding manure distribution will occur
      as they are planned. The discrepancy between planned versus actual outcomes in
      phosphorus management was explored on nine AFOs managing a contiguous set of 210
      fields in south-central Wisconsin. A total of 2611 soil samples were collected
      and multiple interviews conducted to assign phosphorus index (PI) ratings to the
      fields. Spearman's rank correlation coefficients (r(S)) indicated that PI ratings
      were less sensitive to soil test phosphorus (STP) levels (r(S) = 0.378),
      universal soil loss equation (USLE) (r(S) = 0.261), ratings for chemical
      fertilizer application (r(S) = 0.185), and runoff class (r(S) = -0.089), and more
      sensitive to ratings for manure application (r(S) = 0.854). One-way ANOVA
      indicated that mean field STP levels were more homogenous than field PI ratings
      between AFOs. Kolmogorov-Smirnov (K-S) tests displayed several nonsignificant
      comparisons for cumulative distribution functions, S(x), of mean STP levels on
      AFO fields. On the other hand, the K-S tests of S(x) for PI ratings indicated
      that the majority of these S(x) functions were significantly different between
      AFOs at or greater than the 0.05 significance level. Interviews suggested
      multiple reasons for divergence between planned and actual outcomes in managing
      phosphorus, and that this divergence arises at the strategic, tactical, and
      operational levels of decision-making.

PMID- 15843640
TI  - The effect of phosphogypsum on greenhouse gas emissions during cattle manure
      composting.
AB  - Phosphogypsum (PG), a by-product of the phosphate fertilizer industry, reduces N
      losses when added to composting livestock manure, but its impact on greenhouse
      gas emissions is unclear. The objective of this research was to assess the
      effects of PG addition on greenhouse gas emissions during cattle feedlot manure
      composting. Sand was used as a filler material for comparison. The seven
      treatments were PG10, PG20, PG30, S10, S20, and S30, representing the rate of PG
      or sand addition at 10, 20, or 30% of manure dry weight and a check treatment (no
      PG or sand) with three replications. The manure treatments were composted in open
      windrows and turned five times during a 134-d period. Addition of PG
      significantly increased electrical conductivity (EC) and decreased pH in the
      final compost. Total carbon (TC), total nitrogen (TN), and mineral nitrogen
      contents in the final composted product were not affected by the addition of PG
      or sand. From 40 to 54% of initial TC was lost during composting, mostly as
      CO(2), with CH(4) accounting for <14%. The addition of PG significantly reduced
      CH(4) emissions, which decreased exponentially with the compost total sulfur (TS)
      content. The emission of N(2)O accounted for <0.2% of initial TN in the manure,
      increasing as compost pH decreased from alkaline to near neutral. Based on the
      total greenhouse gas budget, PG addition reduced greenhouse gas emissions (CO(2)
      C equivalent) during composting of livestock manure by at least 58%, primarily
      due to reduced CH(4) emission.

PMID- 15843641
TI  - Effect of water table on willows grown in amended mine tailing.
AB  - Survival and growth characteristics of two montane riparian willow species, Geyer
      willow (Salix geyeriana Andersson) and mountain willow (Salix monticola Bebb),
      grown in amended fluvial mine tailing were investigated in a greenhouse study.
      Willow stem cuttings were planted in lysimeters that simulated a 60-cm amended
      tailing profile with three static water depths (20, 40, and 60 cm) and a
      fluctuating water table for a total of four water table treatments. Species and
      water table treatments affected plant biomass and chemical composition of the
      soil and plant tissue. Mountain willow leaf, stem, and root biomass were 62, 95,
      and 164% greater, respectively, than for Geyer willow. Averaging across species,
      the fluctuating water table negatively affected leaf and stem biomass compared
      with the 20- and 60-cm water table treatments. Manganese was the only metal in
      plant tissue to strongly respond to water table treatments. Manganese
      concentrations in mountain willow leaf tissue were approximately twofold higher
      in the two most saturated water table treatments (20 cm and fluctuating) than in
      the least saturated water table treatment (60 cm). This trend was consistent with
      chemical analyses of the growth media, which reflected higher bioavailable Mn in
      the saturated tailing profile compared with the unsaturated profile. Results from
      this study indicate that mountain willow is a more vigorous and possibly more
      metal-tolerant species than Geyer willow when grown in amended mine tailing and
      that a fluctuating water table negatively affects willow growth.

PMID- 15843642
TI  - The acetochlor registration partnership state ground water monitoring program.
AB  - The Acetochlor Registration Partnership (ARP) conducted a 7-yr ground water
      monitoring program at a total of 175 sites in seven states: Illinois, Indiana,
      Iowa, Kansas, Minnesota, Nebraska, and Wisconsin. While acetochlor [2-chloro-N
      (ethoxymethyl)-N-(2-ethyl-6-methylphenyl)-acetamide] was the primary focus, the
      analytical methods also quantified alachlor [2-chloro-N-(2,6-diethylphenyl)-N
      (methoxymethyl)-acetamide], atrazine [6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5
      triazine-2,4-diamine], metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2
      methoxy-1-methylethyl)-acetamide], and two classes of soil degradates for
      acetochlor, alachlor, and metolachlor. Ground water samples were collected
      monthly for five years and quarterly for two additional years. All samples were
      analyzed for the presence of parent herbicides, and degradates were monitored
      during the last three years. Parent acetochlor was detected above 0.1 microg L(
      1) in three or more samples at just seven sites. Alachlor and metolachlor were
      also rarely detected, but atrazine was detected in 36% of all samples analyzed.
      Even more widespread were the tertiary amide sulfonic acid (ethanesulfonic acid,
      ESA) degradates of acetochlor, alachlor, and metolachlor, which were detected at
      81, 76, and 106 sites, respectively. The other class of monitored soil degradates
      (oxanilic acid, OXA) was detected less frequently, at 26, 16, and 63 sites for
      acetochlor OXA, alachlor OXA, and metolachlor OXA, respectively. The geographic
      distribution of detections did not follow the pattern originally expected when
      the study began. Rather than being a function primarily of soil texture, the
      detection of these herbicides in shallow ground water was related to site
      specific factors associated with local topography, the occurrence of surface
      water drainage features, irrigation practices, and the vertical positioning of
      the well screen.

PMID- 15843643
TI  - Identification of the source of nitrate contamination in ground water below an
      agricultural site, Jeungpyeong, Korea.
AB  - This study applied hydrogeological characterization and isotope investigation to
      identify source locations and to trace a plume of ground water contaminated by
      nitrate. Most of the study site is agricultural fields with the remainder being
      residential. A poultry farm is also within the study area, so that potential
      point and nonpoint sources were present. Estimates of seasonal ground water
      recharge from irrigation and precipitation, leakage of sewage, and the regional
      ground water flow were linked to the seasonal changes in isotopic values. Ground
      water recharge largely occurred in spring and summer following precipitation or
      irrigation, depending on the locations. Natural and fertilized soils were
      identified as nonpoint sources of nitrate contamination in this area, while
      septic and animal wastes were identified as small point sources. The seasonal
      changes in the relative impact of these sources on ground water contamination
      were related to such factors as source distribution, the aquifer confining
      condition, precipitation rate, infiltration capacity, recharge rate, and the land
      use pattern.

PMID- 15843644
TI  - Bioproduction of ferric sulfate used during heavy metals removal from sewage
      sludge.
AB  - Toxic metals removal from wastewater sewage sludge can be achieved through
      microbial processes involving Acidithiobacillus ferrooxidans. The oxidation of
      ferrous ions by A. ferrooxidans, cultured in sewage sludge filtrate, was studied
      in both batch and continuous flow stirred tank reactors. Sewage sludge filtrate
      containing natural nutrients (phosphorus and nitrogen) was recovered as effluent
      following the dehydration of a primary and secondary sludge mixture. Batch and
      continuous flow stirred tank reactor tests demonstrated that A. ferrooxidans were
      able to grow and completely oxidize ferrous iron in a culture medium containing
      more than 80% (v v(-1)) sewage sludge filtrate with 10 g Fe(II) L(-1) added.
      Toxic levels were reached when total organic carbon in the sewage sludge filtrate
      exceeded 250 mg L(-1). The ferric iron solution produced in the sludge filtrate
      by A. ferrooxidans was used to solubilize heavy metals in primary and secondary
      sludge. The solubilization of Cu, Cr, and Zn yielded 71, 49, and 80%,
      respectively. This is comparable with the yield percentages obtained using a
      FeCl(3) solution. The cost of treating wastewater sewage sludge by bioproducing a
      ferric ion solution from sewage sludge is three times less expensive than the
      conventional method requiring a commercial ferric chloride solution.

PMID- 15843645
TI  - Understanding long-term baseflow water quality trends using a synoptic survey of
      the ground water-surface water interface, central Wisconsin.
AB  - The relationship between stream water quality and landscape activities is
      difficult to evaluate where the principal source of stream flow is ground water
      seepage because the average travel time from ground water recharge areas to
      stream discharge positions can be on the order of decades. We tested the idea
      that past and future baseflow water quality can be predicted based on a synoptic
      survey of ground water recharge age-dates (based on chlorofluorocarbon [CFC]
      measurements) and water quality measurements obtained at the ground water-surface
      water interface. In this study we (i) characterize the discharge-weighted age
      distribution and water quality of ground water seepage into the Little Plover
      River (LPR); (ii) use this information to backcast and forecast baseflow NO(3)(-)
      concentrations; and (iii) evaluate NO(3)(-) backcasts against historical baseflow
      data (1960 to 2000). The discharge-weighted apparent CFC age of ground water
      seepage into the LPR was 23.7 (+/-7) yr. Baseflow backcasts matched the four
      decade rise of baseflow NO(3)(-) from 2 to 8 mg L(-1). Baseflow forecasts
      included three scenarios. Scenario A projects the historical rise of NO(3)(-) in
      the LPR basin's ground water recharge through 2050. Scenario B projects a
      leveling off of NO(3)(-) in ground water recharge in the year 2000. Scenario C
      projects a leveling off in the year 1985. Under Scenario A, LPR baseflow NO(3)(-)
      will increase steadily from 8 to 19 mg L(-1) between 2000 and 2050. Under
      scenarios B and C baseflow NO(3)(-) will plateau at 13 mg L(-1) in 2030 and at 10
      mg L(-1) in 2010, respectively. The approach developed in this study can be used
      to (i) reconstruct historical baseflow water quality patterns in the absence of
      long-term monitoring data and (ii) project the effects of potential management
      decision on future water quality.

PMID- 15843646
TI  - Distribution and persistence of pyrethroids in runoff sediments.
AB  - Pyrethroids are commonly used insecticides in both agricultural and urban
      environments. Recent studies showed that surface runoff facilitated transport of
      pyrethroids to surface streams, probably by sediment movement. Sediment
      contamination by pyrethroids is of concern due to their wide-spectrum aquatic
      toxicity. In this study, we characterized the spatial distribution and
      persistence of bifenthrin [BF; (2-methyl(1,1'-biphenyl)-3-yl)methyl 3-(2-chloro
      3,3,3-trifluoro-1-propenyl)-2,2-dimethylcyclopropanecarboxylate] and permethrin
      [PM; 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid (3
      phenoxyphenyl)methyl ester] in the sediment along a 260-m runoff path. Residues
      of BF and PM were significantly enriched in the eroded sediment, and the
      magnitude of enrichment was proportional to the downstream distance. At 145 m
      from the sedimentation pond, BF was enriched by >25 times, while PM isomers were
      enriched by >3.5 times. Pesticide enrichment along the runoff path coincided with
      enrichment of organic carbon and clay fractions in the sediment, as well as
      increases in adsorption coefficient K(d), suggesting that the runoff flow caused
      selective transport of organic matter and chemical-rich fine particles. Long
      persistence was observed for BF under both aerobic and anaerobic conditions, and
      the half-life ranged from 8 to 17 mo at 20 degrees C. The long persistence was
      probably caused by the strong pesticide adsorption to the solid phase. The
      significant enrichment, along with the prolonged persistence, suggests that
      movement of pyrethroids to the surface water may be caused predominantly by the
      chemically rich fine particles. It is therefore important to understand the fate
      of sediment-borne pyrethroids and devise mitigation strategies to reduce offsite
      movement of fine sediment.

PMID- 15843647
TI  - Advanced thermal characterization of fractionated natural organic matter.
AB  - This work focuses on an experimental investigation of the thermodynamic
      properties of natural organic matter (NOM), and whether fractions of NOM possess
      the same thermodynamic characteristics as the whole NOM from which they are
      derived. Advanced thermal characterization techniques were employed to quantify
      thermal expansion coefficients (alpha), constant-pressure specific heat
      capacities (C(p)), and thermal transition temperatures (T(t)) of several aquatic-
      and terrestrial-derived NOM. For the first time, glass transition behavior is
      reported for a series of NOM fractions derived from the same whole aquatic or
      terrestrial source, including humic acid-, fulvic acid-, and carbohydrate-based
      NOM, and a terrestrial humin. Thermal mechanical analysis (TMA), standard
      differential scanning calorimetry (DSC), and temperature-modulated differential
      scanning calorimetry (TMDSC) measurements revealed T(t) ranging from -87 degrees
      C for a terrestrial carbohydrate fraction to 62 degrees C for the humin fraction.
      The NOM generally followed a trend of increasing T(t) from carbohydrate to fulvic
      acid to humic acid to humin, and greater T(t) associated with terrestrial
      fractions relative to aquatic fractions, similar to that expected for
      macromolecules possessing greater rigidity and larger molecular weight. Many of
      the NOM samples also possessed evidence of multiple transitions, similar to beta
      and alpha transitions of synthetic macromolecules. The presence of multiple
      transitions in fractionated NOM, however, is not necessarily reflected in whole
      NOM, suggesting other potential influences in the thermal behavior of the whole
      NOM relative to fractionated NOM. Temperature-scanning X-ray diffraction studies
      of each NOM fraction confirmed the amorphous character of each sample through
      T(t).

PMID- 15843648
TI  - Persistence and pathways of testosterone dissipation in agricultural soil.
AB  - The persistence and pathways of dissipation of testosterone in three agricultural
      soils were examined in laboratory microcosm incubations at different soil
      moistures (1.7-39%) and temperatures (4-30 degrees C) using (14)C- and (3)H
      labeled and unlabeled testosterone. Sterilized loam was also examined to assess
      possible abiotic pathways. Extractable (14)C decreased rapidly for all three
      soils at 30 degrees C with times to dissipate 50% of material (DT(50)) ranging
      from 8.5 to 21 h. Respired (14)CO(2) accounted for approximately 50% of the
      applied (14)C after 120 h. Androgenic activity of soil extracts declined faster
      than the extractable (14)C levels demonstrating that testosterone was not being
      converted to compounds with greater activity. Dissipation rates of nonvolatile,
      extractable (3)H in loam at 7, 15, and 39% moisture were similar, but the rate in
      air-dried loam (1.7% moisture) was significantly reduced. High performance liquid
      chromatography (HPLC) analysis of extracts of (14)C-testosterone-treated loam
      incubated at 30 degrees C for 6 h revealed that the (14)C was distributed among
      the remaining testosterone and three major metabolites (4-androstene-3,17-dione,
      5alpha-androstane-3,17-dione, and 1,4-androstadiene-3,17-dione), which accounted
      for 48.7, 23.7, and 9.6% of the remaining (14)C, respectively. Periodic analysis
      of soil incubated at 23, 12, and 4 degrees C showed that the rates of
      testosterone dissipation and metabolite appearance and subsequent dissipation
      were temperature dependent with rates decreasing with decreasing temperature. In
      sterilized loam, 4-androstene-3,17-dione was the only metabolite detected. We
      conclude that testosterone is rapidly and thoroughly biodegraded in agricultural
      soils under a range of conditions typical of a temperate growing season and thus
      is unlikely to pose a long-term risk to adjacent aquatic environments.

PMID- 15843649
TI  - Persistence of testosterone and 17beta-estradiol in soils receiving swine manure
      or municipal biosolids.
AB  - Natural and synthetic steroidal hormones can be carried to agricultural soil
      through fertilization with municipal biosolids, livestock manure, or poultry
      manure. The persistence and pathways of dissipation of [4-(14)C]-testosterone and
      of [4-(14)C]-17beta-estradiol in organic-amended soils were investigated using
      laboratory microcosms. Testosterone dissipation was investigated over a range of
      amendment concentrations, temperatures, and soil types. Under all conditions the
      parent compound and transformation products were dissipated within a few days.
      Addition of swine manure slurry to soil hastened the transformation of
      testosterone and 17beta-estradiol to the corresponding less hormonally active
      ketones, 4-androstene-3,17-dione and estrone. Two other testosterone
      transformation products, 5alpha-androstan-3,17-dione and 1,4-androstadiene-3,17
      dione, were also detected. Experiments with sterilized soil and sterilized swine
      manure slurry suggested that the transformation of (14)C-labeled hormonal parent
      compounds was mainly caused by microorganisms in manure slurry, while
      mineralization of the hormones to (14)CO(2) required viable soil microorganisms.
      Organic amendments transiently inhibited the mineralization of [4-(14)C]
      testosterone, perhaps by inhibiting soil microorganisms, or by enhancing sorption
      and reducing the bioavailability of testosterone or transformation products.
      Overall, organic amendments influenced the pathways and kinetics of testosterone
      and estradiol dissipation, but did not increase their persistence.

PMID- 15843650
TI  - Simple models for phosphorus loss from manure during rainfall.
AB  - Mechanistic, predictive equations for phosphorus (P) transport in runoff from
      manure-applied fields constitute a critical knowledge gap for developing nonpoint
      source pollution models. We derived two simple equations to describe the P
      release from animal manure during a rainfall event-one based on first-order P
      desorption kinetics and one based on second-order kinetics. The manure
      characteristics needed in the two kinetic equations are the maximum amount of
      water-extractable phosphorus (WEP) and a characteristic desorption time. Water
      extractable P can be measured directly but currently the characteristic time can
      only be obtained by fitting experimental data. In addition, we evaluated two
      models usually used to estimate P loss from soil, the Elovitch equation and power
      function, both of which relate P loss to time. The models were tested against
      previously published data of P release from different manures under laboratory
      conditions. All equations fit the data well. Of the two kinetic equations, the
      second-order model showed better agreement with the data than the first-order
      model; for example, maximum relative differences between the model results and
      measured data were 2.6 and 4.7%, respectively. The characteristic times varied
      between 20 min for dairy manure and almost 100 min for poultry manure. The
      characteristic time did not appear to change with flow rate but decreased with
      smaller manure aggregates. The parameters for power-function relationships could
      not be related to measured manure characteristics. These results provide the
      first step to process-based approximations for predicting P release from manure
      with time during rainfall shortly after land application, when P losses are the
      greatest.

PMID- 15843651
TI  - The acetochlor registration partnership surface water monitoring program for four
      corn herbicides.
AB  - A surface drinking water monitoring program for four corn (Zea mays L.)
      herbicides was conducted during 1995-2001. Stratified random sampling was used to
      select 175 community water systems (CWSs) within a 12-state area, with an
      emphasis on the most vulnerable sites, based on corn intensity and watershed
      size. Finished drinking water was monitored at all sites, and raw water was
      monitored at many sites using activated carbon, which was shown capable of
      removing herbicides and their degradates from drinking water. Samples were
      collected biweekly from mid-March through the end of August, and twice during the
      off-season. The analytical method had a detection limit of 0.05 microg L(-1) for
      alachlor [2-chloro-N-(2,6-diethylphenyl)-N-(methoxymethyl)-acetamide] and 0.03
      microg L(-1) for acetochlor [2-chloro-N-(ethoxymethyl)-N-(2-ethyl-6-methylphenyl)
      acetamide], atrazine [6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4
      diamine], and metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1
      methylethyl)-acetamide]. Of the 16528 drinking water samples analyzed,
      acetochlor, alachlor, atrazine, and metolachlor were detected in 19, 7, 87, and
      53% of the samples, respectively. During 1999-2001, samples were also analyzed
      for the presence of six major degradates of the chloroacetanilide herbicides,
      which were detected more frequently than their parent compounds, despite having
      higher detection limits of 0.1 to 0.2 microg L(-1). Overall detection frequencies
      were correlated with product use and environmental fate characteristics.
      Reservoirs were particularly vulnerable to atrazine, which exceeded its 3 microg
      L(-1) maximum contaminant level at 25 such sites during 1995-1999. Acetochlor
      annualized mean concentrations (AMCs) did not exceed its mitigation trigger (2
      microg L(-1)) at any site, and comparisons of observed levels with standard
      measures of human and ecological hazards indicate that it poses no significant
      risk to human health or the environment.

PMID- 15843652
TI  - Phosphate adsorption by ferrihydrite-amended soils.
AB  - New technology and approaches for reducing P in runoff from high sediment yield
      areas are essential due to implementation of increasingly rigorous water quality
      standards. The objectives of this research were to characterize ferrihydrite
      (Fe(5)HO(8).4H(2)O) in terms of its ability to adsorb P from soil solutions and
      relate its P adsorptive capacity to several soil properties that influence P
      mobility. A naturally occurring ferrihydrite, collected as an Fe oxide sludge by
      product from a water treatment facility, was equilibrated with soil samples at
      equivalent rates of 0, 0.34, 3.36, 16.80, and 33.60 Mg ha(-1) for a 60-d period.
      Individual 2-g subsamples of each soil were then equilibrated with 0, 5, 10, 20,
      and 40 mg kg(-1) P in 20 mL of 0.01 M CaCl(2) on a reciprocating shaker for 24 h.
      After 24 h, P in solution was measured by colorimetric methods, and designated as
      final P concentrations. The data indicated that the unamended soils with a pH of
      <6.0 adsorbed, in some cases, 50 times more P than soils with a pH of >7.0. The
      final P concentrations, averaged for all initial P concentrations and
      ferrihydrite rates, ranged from 0.09 to 4.63 mg kg(-1), and were most highly
      correlated with pH (r = 0.844; P < or = 0.01), oxalate-extractable Fe (r = 
      0.699; P < or = 0.10), and dithionite-extractable Fe (r = -0.639; P < or = 0.10)
      contents of the unamended soils. In terms of individual soils, correlation
      coefficients (r) for final P concentrations versus ferrihydrite amendment rates
      indicated a statistically significant (P < or = 0.001) negative relationship at
      all initial P concentrations for most A horizons. The r values for the high Fe
      oxide content B horizon soils did not show a statistically significant response
      to ferrihydrite additions. The results indicate that P adsorption, in soils
      amended with ferrihydrite, will be greatest under acid pH conditions below the
      ferrihydrite zero point of charge (pH 5.77), and low incipient Fe oxide contents.

PMID- 15843653
TI  - Quantifying ground water inputs along the Lower Jordan River.
AB  - The flow rate of the Lower Jordan River has changed dramatically during the
      second half of the 20th century. The diversion of its major natural sources
      reduced its flow rate and led to drying events during the drought years of 2000
      and 2001. Under these conditions of low flow rates, the potential influence of
      external sources on the river discharge and chemical composition became
      significant. Our measurements show that the concentrations of chloride, calcium,
      and sodium in the river water decrease along the first 20-km section, while
      sulfate and magnesium concentrations increase. These variations were addressed by
      a recent geochemical study, suggesting that ground water inflow plays a major
      role. To further examine the role of ground water, we applied mass-balance
      calculations, using detailed flow rate measurements, water samplings, and
      chemical analyses along the northern (upstream) part of the river. Our flow-rate
      measurements showed that the river base-flow during 2000 and 2001 was 500 to 1100
      L s(-1), which is about 40 times lower than the historical flow rates. Our
      measurements and calculations indicate that ground water input was 20 to 80% of
      the river water flow, and 20 to 50% of its solute mass flow. This study
      independently identifies the composition of possible end-members. These end
      members contain high sulfate concentration and have similar chemical
      characteristics as were found in agricultural drains and in the "saline" Yarmouk
      River. Future regional development plans that include the river flow rate and
      chemistry should consider the interactions between the river and its shallow
      ground water system.

PMID- 15843654
TI  - Macroinvertebrate communities in agriculturally impacted southern Illinois
      streams: patterns with riparian vegetation, water quality, and in-stream habitat
      quality.
AB  - Relationships between riparian land cover, in-stream habitat, water chemistry,
      and macroinvertebrates were examined in headwater streams draining an
      agricultural region of Illinois. Macroinvertebrates and organic matter were
      collected monthly for one year from three intensively monitored streams with a
      gradient of riparian forest cover (6, 22, and 31% of riparian area).
      Bioassessments and physical habitat analyses were also performed in these three
      streams and 12 other nearby headwater streams. The intensively monitored site
      with the least riparian forest cover had significantly greater percent silt
      substrates than the sites with medium and high forest cover, and significantly
      higher very fine organics in substrates than the medium and high forested sites.
      Macroinvertebrates were abundant in all streams, but communities reflected
      degraded conditions; noninsect groups, mostly oligochaetes and copepods,
      dominated density and oligochaetes and mollusks, mostly Sphaerium and Physella,
      dominated biomass. Of insects, dipterans, mostly Chironomidae, dominated density
      and dipterans and coleopterans were important contributors to biomass. Collector
      gatherers dominated functional structure in all three intensively monitored
      sites, indicating that functional structure metrics may not be appropriate for
      assessing these systems. The intensively monitored site with lowest riparian
      forest cover had significantly greater macroinvertebrate density and biomass, but
      lowest insect density and biomass. Density and biomass of active collector
      filterers (mostly Sphaerium) decreased with increasing riparian forest.
      Hilsenhoff scores from all 15 sites were significantly correlated with in-stream
      habitat scores, percent riparian forest, and orthophosphate concentrations, and
      multiple regression indicated that in-stream habitat was the primary factor
      influencing biotic integrity. Our results show that these "drainage ditches"
      harbor abundant macroinvertebrates that are typical of degraded conditions, but
      that they can reflect gradients of conditions in and around these streams.

PMID- 15843655
TI  - Transfer of Escherichia coli to water from drained and undrained grassland after
      grazing.
AB  - The aim of this study was to determine the load of Escherichia coli transferred
      via drainage waters from drained and undrained pasture following a grazing
      period. Higher concentrations (ranging between 10(4) and 10(3) colony forming
      units [CFU] g(-1)) of E. coli persisted in soil for up to 60 d beyond the point
      where cattle were removed from the plots, but these eventually declined in the
      early months of spring to concentrations less than 10(2) CFU g(-1). The decline
      reflects the combined effect of cell depletion from the soil store through both
      wash-out and die-off of E. coli. No difference (P > 0.05) was observed in E. coli
      loads exported from drained and undrained plots. Similarly, no difference (P >
      0.05) was observed in E. coli concentrations in drainage waters of mole drain
      flow and overland plus subsurface interflow. Intermittent periods of elevated
      discharge associated with storm events mobilized E. coli at higher concentrations
      (e.g., in excess of 400 CFU mL(-1)) than observed during low flow conditions
      (often <25 CFU mL(-1)). The combination of high discharge and cell concentrations
      resulted in the export of E. coli loads from drained and undrained plots
      exceeding 10(6) CFU L(-1) s(-1). The results highlight the potential for drained
      land to export E. coli loads comparable with those transferred from undrained
      pasture.

PMID- 15843656
TI  - Colloidal and dissolved phosphorus in sandy soils as affected by phosphorus
      saturation.
AB  - Fertilization exceeding crop requirements causes an accumulation of phosphorus
      (P) in soils, which might increase concentrations of dissolved and colloidal P in
      drainage. We sampled soils classified as Typic Haplorthods from four
      fertilization experiments to test (i) whether increasing degrees of phosphorus
      saturation (DPS) increase concentrations of dissolved and colloidal P, and (ii)
      if critical DPS levels can be defined for P release from these soils. Oxalate
      extractable concentrations of P, iron (Fe), and aluminum (Al) were quantified to
      characterize DPS. Turbidity, zeta potential, dissolved P, and colloidal P, Fe,
      Al, and carbon (C) concentrations were determined in water and KCl extracts.
      While concentrations of dissolved P decreased with increasing depth,
      concentrations of water-extractable colloidal P remained constant. In topsoils 28
      +/- 17% and in subsoils 94 +/- 8% of water-extractable P was bound to colloids.
      Concentrations of dissolved P increased sharply for DPS > 0.1. Colloidal P
      concentrations increased with increasing DPS because of an additional
      mobilization of colloids and due to an increase of the colloids P contents. In
      addition to DPS, ionic strength and Ca(2+) affected the release of colloidal P.
      Hence, using KCl for extraction improved the relationship between DPS and
      colloidal P compared with water extraction. Accumulation of P in soils increases
      not only concentrations of dissolved P but also the risk of colloidal P
      mobilization. Leaching of colloidal P is potentially important for inputs of P
      into water bodies because colloidal P as the dominant water-extractable P
      fraction in subsoils was released from soils with relatively low DPS.

PMID- 15843657
TI  - Nitrogen removal in laboratory model leachfields with organic-rich layers.
AB  - Septic system leachfields can release dissolved nitrogen in the form of nitrate
      into ground water, presenting a significant source of pollution. Low cost,
      passive modifications, which increase N removal in traditional leachfields, could
      substantially reduce the overall impact on ground water resources. Bench-scale
      laboratory models were constructed to evaluate the effect of placing an organic
      layer below the leachfield on total N removal. The organic layer provides a
      carbon source for denitrification. Column units representing septic leachfields
      were constructed with sawdust-native soil organic layers placed 0.45 m below the
      influent line and with thicknesses of 0.0, 0.3, 0.6, and 0.9 m. Using a synthetic
      septic tank effluent, NO(3)-N concentrations at 3.8 m below the influent line
      were consistently below 1 mg L(-1) during 10 months of operation compared with a
      NO(3)-N concentration of nearly 12 mg L(-1) in the control column. The average
      total N removal increased from 31% without the organic layer to 67% with the
      organic layer. Total N removal appeared limited by the extent of organic N
      oxidation and nitrification in the 0.45-m aerobic zone. Design modifications
      targeted at improving nitrification above the organic layer may further increase
      total N removal. Increased organic layer thicknesses from 0.3 m to 0.9 m did not
      significantly improve average total N removal, but caused a shift in residual
      nitrogen from organic N to ammonia N. Results indicate that addition of a layer
      of carbon source material at least 0.3 m thick below a standard leachfield
      substantially improves total N removal.

PMID- 15843658
TI  - Decrease in water-soluble 17beta-Estradiol and testosterone in composted poultry
      manure with time.
AB  - Little attention has been paid to the environmental fate of the hormones 17beta
      estradiol and testosterone excreted in animal waste. Land application of manure
      has a considerable potential to affect the environment with these endocrine
      disrupting compounds (EDCs). Composting is known to decompose organic matter to a
      stable, humus-like material. The goal of the present study was to quantitatively
      assess levels of water-soluble 17beta-estradiol and testosterone in composting
      chicken manure with time. Chicken layer manure was mixed with hay, straw,
      decomposed leaves, and starter compost, adjusted to approximately 60% moisture,
      and placed into a windrow. A clay-amended windrow was also prepared. Windrows
      were turned weekly, and temperature, oxygen, and CO(2) in the composting mass
      were monitored for either 133 or 139 d. Commercial enzyme immunoassay kits were
      used to quantitate the levels of 17beta-estradiol and testosterone in aqueous
      sample extracts. Water-soluble quantities of both hormones diminished during
      composting. The decrease in 17beta-estradiol followed first-order kinetics, with
      a rate constant k = -0.010/d. Testosterone levels declined at a slightly higher
      rate than 17beta-estradiol (i.e., k = -0.015/d). Both hormones could still be
      measured in aqueous extracts of compost sampled at the conclusion of composting.
      The decline in water-soluble 17beta-estradiol and testosterone in extracts of
      clay-amended compost was not statistically different from normal compost. These
      data suggest that composting may be an environmentally friendly technology
      suitable for reducing, but not eliminating, the concentrations of these endocrine
      disrupting hormones at concentrated animal operation facilities.

PMID- 15843659
TI  - Evaluation of soils for use as liner materials: a soil chemistry approach.
AB  - Movement of NH(4)(+) below animal waste lagoons is generally a function of the
      whole-lagoon seepage rate, soil mineralogy, cations in the lagoon liquor, and
      selectivity for NH(4)(+) on the soil-exchange sites. Binary exchange reactions
      (Ca(2+)-K(+), Ca(2+)-NH(4)(+), and K(+)-NH(4)(+)) were conducted on two soils
      from the Great Plains and with combinations of these soils with bentonite or
      zeolite added. Binary exchanges were used to predict ternary exchanges Ca(2+)
      K(+)-NH(4)(+) following the Rothmund-Kornfeld approach and Gaines-Thomas
      convention. Potassium and NH(4)(+) were preferred over Ca(2+), and K(+) was
      preferred over NH(4)(+) in all soils and soils with amendments. Generally, the
      addition of bentonite did not change cation selectivity over the native soils,
      whereas the addition of zeolite did. The Rothmund-Kornfeld approach worked well
      for predicting equivalent fractions of cations on the exchanger phase when only
      ternary-solution phase compositions were known. Actual swine- and cattle-lagoon
      solution compositions and the Rothmund-Kornfeld approach were used to project
      that native soils are predicted to retain 53 and 23%, respectively, of the
      downward-moving NH(4)(+) on their exchange sites. Additions of bentonite or
      zeolite to soils under swine lagoons may only slightly improve the equivalent
      fraction of NH(4)(+) on the exchange sites. Although additions of bentonite or
      zeolite may not help increase the NH(4)(+) selectivity of a liner material,
      increases in the overall cation exchange capacity (CEC) of a soil will ultimately
      decrease the amount of soil needed to adsorb downward-moving NH(4)(+).

PMID- 15843660
TI  - Field-scale application of oily food waste and nitrogen fertilizer requirements
      of corn at different landscape positions.
AB  - Oily food waste (FOG; fat + oil + greases) containing high concentrations of fat,
      oil and grease is produced by the food service, production, and processing
      industries. It has a high C to N ratio (90:1) and can recycle soil available N
      through immobilization and remineralization during its decomposition. Experiments
      were conducted at a farm (Hillsburg fine sandy loam; Typic Hapludalf) having
      rolling topography (5 and 9% slope) during 1995 and 1996. Objectives of this
      study were to (i) examine the variability of available N and corn (Zea mays L.)
      grain yield at different landscape positions of FOG-amended fields and (ii)
      determine whether N fertilizer management could be improved by considering the
      spatial variability of soil NO(3)-N at different landscape positions in FOG
      amended fields. A spatial and temporal variability in soil NO(3)-N was observed
      during both years. Corn grain yields at all N fertilizer application rates were
      affected by slope position and followed the pattern: lower > upper > or = middle.
      Nitrogen fertilizer requirements for corn production in conjunction with FOG
      management were also affected by slope position. Essentially no additional
      fertilizer N was required for corn production at the lower landscape position. It
      was estimated that site-specific fertilizer N management on FOG-amended fields
      could result in an average savings of 51 and 63 kg N ha(-1) (with a potential
      economical savings of US 42 dollars and US 52 dollars ha(-1)) during 1995 and
      1996, respectively.

PMID- 15843661
TI  - Phosphorus extractability of soils amended with stockpiled and composted cattle
      manure.
AB  - Managing fertilizer applications to maintain soil P below environmentally
      unacceptable levels should consider the contribution of manure and synthetic
      fertilizer sources to soluble and extractable forms of P. Our objective was to
      evaluate soil and manure characteristics and application rates on P
      extractability in recently amended soils. Five soils of the U.S. southern High
      Plains were amended with beef cattle manures, composted beef manure, and
      inorganic fertilizers [Ca(H(2)PO(4))(2) or KH(2)PO(4)] at five rates and
      incubated under controlled conditions. Mehlich 3-, Olsen (NaHCO(3))-, Texas A&M
      extractant (TAM)-, and water-extractable P were determined for the soils after
      selected incubation periods. Except for TAM and some water extractions, P
      extractability as a function of total P applied was linear (P < 0.001) for a wide
      range of application rates. Mehlich-3, NaHCO(3), and water P extraction
      efficiencies of KH(2)PO(4)-amended soils averaged 22, 34, and 115% greater (P <
      or = 0.036), respectively, than efficiencies of soils amended with manures except
      for the Texline (calcareous) loam and Pullman clay loam soils. Phosphorus
      extraction efficiencies decreased with time for KH(2)PO(4)-amended soils (P <
      0.05) but remained stable or increased for manure-amended soils during the 8-wk
      incubation period. Across all soils and manure sources, changes in water
      extractable P per unit increase in Mehlich 3-, NaHCO(3)-, and TAM-extractable P
      averaged 100, 85, and 125% greater, respectively, for inorganic as compared with
      manure-amended soils. These source-dependent relationships limit the use of
      agronomic soil extractants to make correct inferences about water-extractable P
      and dissolved P in runoff.

PMID- 15843662
TI  - Images in clinical medicine. Disseminated gonococcal infection.

PMID- 15843663
TI  - Physician-assisted suicide--Oregon and beyond.

PMID- 15843664
TI  - The million dollar question.

PMID- 15843665
TI  - A new colonialism?--Conducting clinical trials in India.

PMID- 15843666
TI  - Azithromycin for the secondary prevention of coronary events.
AB  - BACKGROUND: Epidemiologic, laboratory, animal, and clinical studies suggest that
      there is an association between Chlamydia pneumoniae infection and atherogenesis.
      We evaluated the efficacy of one year of azithromycin treatment for the secondary
      prevention of coronary events. METHODS: In this randomized, prospective trial, we
      assigned 4012 patients with documented stable coronary artery disease to receive
      either 600 mg of azithromycin or placebo weekly for one year. The participants
      were followed for a mean of 3.9 years at 28 clinical centers throughout the
      United States. RESULTS: The primary end point, a composite of death due to
      coronary heart disease, nonfatal myocardial infarction, coronary
      revascularization, or hospitalization for unstable angina, occurred in 446 of the
      participants who had been randomly assigned to receive azithromycin and 449 of
      those who had been randomly assigned to receive placebo. There was no significant
      risk reduction in the azithromycin group as compared with the placebo group with
      regard to the primary end point (risk reduction, 1 percent [95 percent confidence
      interval, -13 to 13 percent]). There were also no significant risk reductions
      with regard to any of the components of the primary end point, death from any
      cause, or stroke. The results did not differ when the participants were
      stratified according to sex, age, smoking status, presence or absence of diabetes
      mellitus, or C. pneumoniae serologic status at baseline. CONCLUSIONS: A one-year
      course of weekly azithromycin did not alter the risk of cardiac events among
      patients with stable coronary artery disease.

PMID- 15843667
TI  - Antibiotic treatment of Chlamydia pneumoniae after acute coronary syndrome.
AB  - BACKGROUND: Chlamydia pneumoniae has been found within atherosclerotic plaques,
      and elevated titers of antibody to this organism have been linked to a higher
      risk of coronary events. Pilot studies have suggested that antibiotic treatment
      may reduce the risk of cardiovascular events. METHODS: We enrolled 4162 patients
      who had been hospitalized for an acute coronary syndrome within the preceding 10
      days and evaluated the efficacy of long-term treatment with gatifloxacin, a
      bactericidal antibiotic known to be effective against C. pneumoniae, in a double
      blind, randomized, placebo-controlled trial. Subjects received 400 mg of
      gatifloxacin daily during an initial 2-week course of therapy that began 2 weeks
      after randomization, followed by a 10-day course every month for the duration of
      the trial (mean duration, 2 years), or placebo. The primary end point was a
      composite of death from all causes, myocardial infarction, documented unstable
      angina requiring rehospitalization, revascularization (performed at least 30 days
      after randomization), and stroke. RESULTS: A Kaplan-Meier analysis revealed that
      the rates of primary-end-point events at two years were 23.7 percent in the
      gatifloxacin group and 25.1 percent in the placebo group (hazard ratio, 0.95; 95
      percent confidence interval, 0.84 to 1.08; P=0.41). No benefit was seen in any of
      the prespecified secondary end points or in any of the prespecified subgroups,
      including patients with elevated titers to C. pneumoniae or C-reactive protein.
      CONCLUSIONS: Despite long-term treatment with a bactericidal antibiotic effective
      against C. pneumoniae, no reduction in the rate of cardiovascular events was
      observed.

PMID- 15843668
TI  - Leflunomide or methotrexate for juvenile rheumatoid arthritis.
AB  - BACKGROUND: We compared the safety and efficacy of leflunomide with that of
      methotrexate in the treatment of polyarticular juvenile rheumatoid arthritis in a
      multinational, randomized, controlled trial. METHODS: Patients 3 to 17 years of
      age received leflunomide or methotrexate for 16 weeks in a double-dummy, blinded
      fashion, followed by a 32-week blinded extension. The rates of American College
      of Rheumatology Pediatric 30 percent responses (ACR Pedi 30) and the Percent
      Improvement Index were assessed at baseline and every 4 weeks for 16 weeks and
      every 8 weeks during the 32-week extension study. RESULTS: Of 94 patients
      randomized, 86 completed 16 weeks of treatment, 70 of whom entered the extension
      study. At week 16, more patients in the methotrexate group than in the
      leflunomide group had an ACR Pedi 30 response (89 percent vs. 68 percent,
      P=0.02), whereas the values for the Percent Improvement Index did not differ
      significantly (-52.87 percent vs. -44.41 percent, P=0.18). In both groups, the
      improvements achieved at week 16 were maintained at week 48. The most common
      adverse events in both groups included gastrointestinal symptoms, headache, and
      nasopharyngeal symptoms. Aminotransferase elevations were more frequent with
      methotrexate than with leflunomide during the initial study and the extension
      study. CONCLUSIONS: In patients with polyarticular juvenile rheumatoid arthritis,
      methotrexate and leflunomide both resulted in high rates of clinical improvement,
      but the rate was slightly greater for methotrexate. At the doses used in this
      study, methotrexate was more effective than leflunomide.

PMID- 15843669
TI  - Familial cancer associated with a polymorphism in ARLTS1.
AB  - BACKGROUND: The finding of hemizygous or homozygous deletions at band 14 on
      chromosome 13 in a variety of neoplasms suggests the presence of a tumor
      suppressor locus telomeric to the RB1 gene. METHODS: We studied samples from 216
      patients with various types of sporadic tumors or idiopathic pancytopenia,
      peripheral-blood samples from 109 patients with familial cancer or multiple
      cancers, and control blood samples from 475 healthy people or patients with
      diseases other than cancer. We performed functional studies of cell lines lacking
      ARLTS1 expression with the use of both the full-length ARLTS1 gene and a
      truncated variant. RESULTS: We found a gene at 13q14, ARLTS1, a member of the ADP
      ribosylation factor family, with properties of a tumor-suppressor gene. We
      analyzed 800 DNA samples from tumors and blood cells from patients with sporadic
      or familial cancer and controls and found that the frequency of a nonsense
      polymorphism, G446A (Trp149Stop), was similar in controls and patients with
      sporadic tumors but was significantly more common among patients with familial
      cancer than among those in the other two groups (P=0.02; odds ratio, 5.7; 95
      percent confidence interval, 1.3 to 24.8). ARLTS1 was down-regulated by promoter
      methylation in 25 percent of the primary tumors we analyzed. Transfection of wild
      type ARLTS1 into A549 lung-cancer cells suppressed tumor formation in
      immunodeficient mice and induced apoptosis, whereas transfection of truncated
      ARLTS1 had a limited effect on apoptosis and tumor suppression. Microarray
      analysis revealed that the wild-type and Trp149Stop-transfected clones had
      different expression profiles. CONCLUSIONS: A genetic variant of ARLTS1
      predisposes patients to familial cancer.

PMID- 15843670
TI  - Clinical practice. Rehabilitation after stroke.

PMID- 15843671
TI  - Inflammation, atherosclerosis, and coronary artery disease.

PMID- 15843672
TI  - Images in clinical medicine. Stevens-Johnson syndrome.

PMID- 15843673
TI  - Case records of the Massachusetts General Hospital. Case 12-2005. A 30-year-old
      woman with a mediastinal mass.

PMID- 15843674
TI  - Infection, antibiotics, and atherothrombosis--end of the road or new beginnings?

PMID- 15843675
TI  - Clopidogrel versus aspirin and esomeprazole to prevent recurrent bleeding.

PMID- 15843676
TI  - Outcomes associated with a trial of labor after prior cesarean delivery.

PMID- 15843677
TI  - Pegaptanib and age-related macular degeneration.

PMID- 15843678
TI  - Cardiovascular risk and body-fat abnormalities in HIV-infected adults.

PMID- 15843679
TI  - Case 35-2004: nephrogenic fibrosing dermopathy.

PMID- 15843680
TI  - Pulmonary adenocarcinomas with mutant epidermal growth factor receptors.

PMID- 15843681
TI  - Remission of macroglobulinemia during anastrozole treatment for breast cancer.

PMID- 15843682
TI  - Analysis of scanning force microscopy images of protein-induced DNA bending using
      simulations.
AB  - Bending of DNA is a feature essential to the function of many DNA-binding
      proteins. Bending angles can be estimated with a variety of techniques, but most
      directly from images obtained using scanning force microscopy (SFM). Direct
      measurement of the bending angle using a tangent method often produces angles
      that deviate significantly from values obtained using other techniques. Here, we
      describe the application of SFM in combination with simulations of DNA as a means
      to estimate protein-induced bending angles in a reliable and unbiased fashion. In
      this manner, we were able to obtain accurate estimates for the bending angles
      induced by nuclear factor I, octamer-binding transcription factor 1, the human
      XPC-Rad23B complex and integration host factor [correction]

PMID- 15843683
TI  - Predicting the secondary structures and tertiary interactions of 211 group I
      introns in IE subgroup.
AB  - The large number of currently available group I intron sequences in the public
      databases provides opportunity for studying this large family of structurally
      complex catalytic RNA by large-scale comparative sequence analysis. In this
      study, the detailed secondary structures of 211 group I introns in the IE
      subgroup were manually predicted. The secondary structure-favored alignments
      showed that IE introns contain 14 conserved stems. The P13 stem formed by long
      range base-pairing between P2.1 and P9.1 is conserved among IE introns. Sequence
      variations in the conserved core divide IE introns into three distinct minor
      subgroups, namely IE1, IE2 and IE3. Co-variation of the peripheral structural
      motifs with core sequences supports that the peripheral elements function in
      assisting the core structure folding. Interestingly, host-specific structural
      motifs were found in IE2 introns inserted at S516 position. Competitive base
      pairing is found to be conserved at the junctions of all long-range paired
      regions, suggesting a possible mechanism of establishing long-range base-pairing
      during large RNA folding. These findings extend our knowledge of IE introns,
      indicating that comparative analysis can be a very good complement for deepening
      our understanding of RNA structure and function in the genomic era.

PMID- 15843684
TI  - Pre-mRNA processing enhancer (PPE) elements from intronless genes play additional
      roles in mRNA biogenesis than do ones from intron-containing genes.
AB  - Most mRNA-encoding genes require introns for efficient expression in high
      eukaryotes. However, mRNAs can efficiently accumulate in the cytoplasm without
      intron excision if they contain cis-acting elements such as the post
      transcriptional regulatory element (PRE) of hepatitis B virus (HBV), the
      constitutive transport element (CTE) of Mason-Pfizer monkey virus (MPMV), or the
      pre-mRNA processing enhancer (PPE) of herpes simplex virus' thymidine kinase (HSV
      TK) gene. We compared the activities of these viral elements, the Rev-responsive
      element (RRE) of the human immunodeficiency virus (HIV), and the human c-Jun
      gene's enhancer (CJE), an element newly identified here, to enable expression of
      an intronless variant of the human beta-globin gene. The PRE, PPE and CJE from
      naturally intronless genes, but not the CTE or RRE from intron-containing genes,
      significantly enhanced stability, 3' end processing and cytoplasmic accumulation.
      When the transcripts included the beta-globin gene's first intron, the PRE, PPE
      and CJE still enhanced mRNA biogenesis, in some cases without intron excision.
      Thus, elements enabling stability, 3' end formation and nucleocytoplasmic export,
      not the presence of introns or their excision per se, are necessary for mRNA
      biogenesis. While the CTE and RRE primarily enhance nucleocytoplasmic export, PPE
      like elements from naturally intronless genes facilitate polyadenylation as well.

PMID- 15843685
TI  - Nematode selenoproteome: the use of the selenocysteine insertion system to decode
      one codon in an animal genome?
AB  - Selenocysteine (Sec) is co-translationally inserted into selenoproteins in
      response to codon UGA with the help of the selenocysteine insertion sequence
      (SECIS) element. The number of selenoproteins in animals varies, with humans
      having 25 and mice having 24 selenoproteins. To date, however, only one
      selenoprotein, thioredoxin reductase, has been detected in Caenorhabditis
      elegans, and this enzyme contains only one Sec. Here, we characterize the
      selenoproteomes of C.elegans and Caenorhabditis briggsae with three independent
      algorithms, one searching for pairs of homologous nematode SECIS elements,
      another searching for Cys- or Sec-containing homologs of potential nematode
      selenoprotein genes and the third identifying Sec-containing homologs of
      annotated nematode proteins. These methods suggest that thioredoxin reductase is
      the only Sec-containing protein in the C.elegans and C.briggsae genomes. In
      contrast, we identified additional selenoproteins in other nematodes. Assuming
      that Sec insertion mechanisms are conserved between nematodes and other
      eukaryotes, the data suggest that nematode selenoproteomes were reduced during
      evolution, and that in an extreme reduction case Sec insertion systems probably
      decode only a single UGA codon in C.elegans and C.briggsae genomes. In addition,
      all detected genes had a rare form of SECIS element containing a guanosine in
      place of a conserved adenosine present in most other SECIS structures, suggesting
      that in organisms with small selenoproteomes SECIS elements may change rapidly.

PMID- 15843686
TI  - Factors affecting translation at the programmed -1 ribosomal frameshifting site
      of Cocksfoot mottle virus RNA in vivo.
AB  - The ratio between proteins P27 and replicase of Cocksfoot mottle virus (CfMV) is
      regulated via a -1 programmed ribosomal frameshift (-1 PRF). A minimal frameshift
      signal with a slippery U UUA AAC heptamer and a downstream stem-loop structure
      was inserted into a dual reporter vector and directed -1 PRF with an efficiency
      of 14.4 +/- 1.9% in yeast and 2.4 +/- 0.7% in bacteria. P27-encoding CfMV
      sequence flanking the minimal frameshift signal caused approximately 2-fold
      increase in the -1 PRF efficiencies both in yeast and in bacteria. In addition to
      the expected fusion proteins, termination products ending putatively at the
      frameshift site were found in yeast cells. We propose that the amount of
      premature translation termination from control mRNAs played a role in determining
      the calculated -1PRF efficiency. Co-expression of CfMV P27 with the dual reporter
      vector containing the minimal frameshift signal reduced the production of the
      downstream reporter, whereas replicase co-expression had no pronounced effect.
      This finding allows us to propose that CfMV protein P27 may influence translation
      at the frameshift site but the mechanism needs to be elucidated.

PMID- 15843688
TI  - Enzymatic processing of replication and recombination intermediates by the
      vaccinia virus DNA polymerase.
AB  - Poxvirus DNA polymerases play a critical role in promoting virus recombination.
      To test if vaccinia polymerase (E9L) could mediate this effect by catalyzing the
      post-synaptic processing of recombinant joint molecules, we prepared substrates
      bearing a nick, a 3'-unpaired overhang, a 5' overhang, or both 3' and 5'
      overhangs. The sequence of the 5' overhang was also modified to permit or
      preclude branch migration across the joint site. These substrates were incubated
      with E9L, and the fate of the primer strand characterized under steady-state
      reaction conditions. E9L rapidly excises a mispaired 3' strand from a DNA duplex,
      producing a meta-stable nicked molecule that is a substrate for ligase. The
      reaction was not greatly affected by adding an unpaired 5' strand, but since such
      molecules cannot be processed into nicked intermediates, the 3'-ended strand
      continued to be subjected to exonucleolytic attack. Incorporating homology into
      the 5' overhang prevented this and permitted some strand assimilation, but such
      substrates also promoted strand-displacement DNA synthesis of a type predicted by
      the 1981 Moyer and Graves model for poxvirus replication. Single-strand annealing
      reactions are used by poxviruses to produce recombinant viruses and these data
      show that virus DNA polymerases can process DNA in such a manner as to both
      generate single-stranded substrates for such reactions and to facilitate the
      final processing of the reaction products.

PMID- 15843687
TI  - Cryptic promoter activity in the DNA sequence corresponding to the pim-1 5'-UTR.
AB  - The serine/threonine kinase pim-1 mRNA contains a long and G/C rich 5'
      untranslated region (5'-UTR). Previous work suggested that the pim-1 5'-UTR
      harbors an internal ribosomal entry site (IRES) allowing for internal initiation
      of translation. However, several previously reported eukaryotic IRES elements
      actually contain cryptic promoter activity. To test whether an IRES or a cryptic
      promoter is present in the pim-1 5'-UTR, the 5'-UTR was re-examined using
      stringent test procedures. Our results show the presence of strong promoter
      activity in the DNA sequence corresponding to the pim-1 5'-UTR. Both promoterless
      dicistronic test and northern blot analysis show transcripts being derived from
      the cryptic promoter in the pim-1 5'-UTR sequence. This cryptic promoter is
      active in all cell types tested, including Cos-7, NIH3T3, HEK293, Jurkat and K562
      cells. When a dicistronic mRNA containing the pim-1 5'-UTR was translated in
      vitro or in vivo, no IRES activity could be detected. However, the control IRESs
      from both human rhinovirus and encephalomyocarditis virus exhibited strong IRES
      activities. In addition, both the RNase protection assay and the 5'-RACE assay
      detected endogenous pim-1 transcripts with shorter 5'-UTRs. Our data strongly
      suggest that the IRES activity reported earlier for the pim-1 5'-UTR sequence is
      due to cryptic promoter activity.

PMID- 15843689
TI  - Harden my heart.

PMID- 15843690
TI  - Sins of synuclein.

PMID- 15843691
TI  - Defining the diet.

PMID- 15843694
TI  - Physician extenders in the emergency department.

PMID- 15843695
TI  - Rabies: a review of UK management.
AB  - Rabies is endemic worldwide, and causes approximately 30 000 deaths per year. In
      the past 20 years, 12 deaths have occurred in the UK, although all but one case
      were contracted overseas. We have reviewed the current literature regarding the
      management of possible rabies exposure in the setting of a UK emergency
      department. The article offers an overview of rabies, including pathology, risk
      assessment, and current treatment, including both pre-exposure and post-exposure
      prophylaxis. We have also included a form online, which allows the correct
      information to be obtained and recorded prior to seeking advice from the local
      virology services.

PMID- 15843696
TI  - Commentary from the front lines: American physician assistants working in a
      United Kingdom emergency department.
AB  - Physician assistants (PAs) have been an integral part of the emergency medicine
      team in the USA for the past 30 years. This review outlines the reasons why PAs
      can play a vital role in UK National Health Service (NHS). The experience of
      American PAs working in one NHS trust are discussed, highlighting the cultural
      differences in the environment of the emergency departments in the two countries
      that will influence the scope of practice of PAs in the UK.

PMID- 15843697
TI  - A comparative study of continuous positive airway pressure (CPAP) and
      intermittent positive pressure ventilation (IPPV) in patients with flail chest.
AB  - INTRODUCTION: The role of non-invasive positive pressure ventilation delivered
      through a face mask in patients with flail chest is uncertain. We conducted a
      prospective, randomised study of continuous positive airway pressure (CPAP) given
      via a face mask to spontaneously breathing patients compared with intermittent
      positive pressure ventilation (IPPV) with endotracheal intubation (ETI) in 52
      patients with flail chest who required mechanical ventilation. METHOD: The 52
      mechanically ventilated patients were randomly divided into two treatment groups:
      the ET group (n = 27) received mechanical ventilation with ETI, whereas patients
      in the CPAP group (n = 25) received CPAP via a face mask with patient controlled
      analgesia (PCA). Major complications, arterial blood gas levels, length of
      intensive care unit (ICU) stay and ICU survival rate were recorded. RESULTS:
      Nosocomial infection was diagnosed in 10 of 21 patients in the ET group, but only
      in 4 of 22 in the CPAP group (p = 0.001). Mean PO(2) was significantly higher in
      the ET group in the first 2 days (p<0.05). There were no significant differences
      in length of ICU stay between groups. Twenty CPAP patients survived, but only 14
      of 21 intubated patients who received IPPV (p<0.01). CONCLUSION: Non-invasive
      CPAP with PCA led to lower mortality and a lower nosocomial infection rate, but
      similar oxygenation and length of ICU stay. The study supports the application of
      CPAP at least as a first line of treatment for flail chest caused by blunt
      thoracic trauma.

PMID- 15843698
TI  - Pitfalls in the clinical diagnosis of vertebral fractures: a case series in which
      posterior midline tenderness was absent.
AB  - OBJECTIVE: There is widespread belief among doctors that posterior midline
      tenderness is virtually a prerequisite for spinal fracture in alert, sober
      patients without any painful distracting injury or neurological deficit. This
      paper examines and challenges this belief. METHODS AND RESULTS: We present three
      patients in whom significant thoracic and lumbar vertebral fractures were missed,
      or were thought to be "old", because of lack of posterior midline tenderness. We
      also present two further patients, one with a lumbar spine fracture and one with
      a cervical spine fracture, in whom posterior midline tenderness was absent but in
      whom the correct diagnosis was made. All these patients were sober and fully
      alert and none had a neurological deficit or a painful distracting injury.
      CONCLUSION: The absence of posterior midline tenderness does not exclude
      significant spinal injury. We suggest that patients should satisfy both the
      Canadian and British guidelines before it is decided that imaging of the cervical
      spine is unnecessary.

PMID- 15843699
TI  - Emergency department ultrasound (EDU): clinical adjunct or plaything?
AB  - BACKGROUND: Emergency department ultrasound (EDU) is a physician performed
      ultrasound service aimed at improving patient flow and diagnosis in the emergency
      department. METHODS: This paper describes the initial phase of the introduction
      of EDU with three illustrative case reports and a discussion on the pitfalls and
      benefits of EDU. RESULTS AND DISCUSSION: In three cases discussed here, the use
      of EDU facilitated treatment and reduced the need for formal radiological
      scanning. While there are drawbacks to EDU, we believe these are far outweighed
      by the advantages, and in a recent survey of emergency medicine consultants
      throughout Ireland, the vast majority were in favour of its introduction.
      CONCLUSION: EDU has become a routine part of our clinical practice, and although
      we are still on a learning curve with regard to its use, we have experienced
      significant benefits in patient care. With technological advances (such as
      improved image resolution and teleradiology) the potential for EDU will continue
      to expand, but training, practice, accreditation, and audit are essential.

PMID- 15843700
TI  - Scapular manipulation technique for reduction of traumatic anterior shoulder
      dislocations: experiences of an academic emergency department.
AB  - BACKGROUND: Shoulder dislocations account for almost 50% of all joint
      dislocations, which are most commonly anterior (90-98%) and occur due to trauma.
      This prospective study was conducted to report our experiences of using the
      scapular manipulation technique (SMT) to reduce traumatic anterior shoulder
      dislocations. METHODS: Between March 2002 and March 2003, SMT was applied to 41
      patients who presented with traumatic anterior shoulder dislocation to the
      Gulhane Military Medical Academy, Department of Emergency Medicine, Ankara,
      Turkey, which is a level 1 trauma centre with an annual attendance of 85,000
      patients. The technique was applied to patients in the prone position by a single
      operator. Where necessary, a procedural sedation/analgesia (PSA) protocol was
      followed. RESULTS: The study population consisted of 26 (63.4%) male patients
      aged between 17 and 76 years (SD 15.6). History of recurrent shoulder
      dislocations at the same site were taken from seven (17.1%) of the patients. Mean
      (SD) trauma to reduction time was approximately 61.5 (72) minutes (range 10-480).
      Five patients (12%) had a greater tuberosity fracture. SMT was attempted twice to
      only four (9.8%) patients by a standard PSA protocol. We experienced a success
      rate of 90.2% at the first attempt and 100% overall. None of the patients
      encountered any complication. CONCLUSIONS: We report the successful use of SMT in
      the prone position for the reduction of traumatic anterior shoulder dislocations,
      mainly without requirement of any sedatives or opiate analgesics. We believe that
      SMT may also be applied by inexperienced physicians, as it is simple, applicable,
      and easily understood. As no single method has a 100% success rate, SMT is a
      useful one to know.

PMID- 15843701
TI  - Trauma calls: role of the general surgeon and CT scanning.
AB  - BACKGROUND AND OBJECTIVE: General surgeons are required in only a minority of
      trauma call cases to assess for abdominal injuries. Computed tomography (CT)
      accurately detects blunt abdominal injuries and may have replaced the need for
      general surgeons at trauma calls. This study evaluated the role of general
      surgeons at trauma calls and assessed use of CT in cases of suspected abdominal
      trauma. METHODS: (a) Eighteen month analysis of trauma calls at a district
      general hospital and (b) three month prospective study of all trauma cases
      presenting to A&E. RESULTS: (a) There were 73 trauma calls and the mechanism of
      injury in most cases was a road traffic accident (RTA). Most patients had
      orthopaedic and/or neurosurgical injuries. The general surgeons assessed 22
      trauma call patients. Abdominal injury was excluded in 13 (four by clinical
      examination and nine following CT). (b) Forty three patients fulfilled the
      criteria for a trauma call and 14 trauma calls were made. The mechanism of injury
      in most was RTA and most had orthopaedic and/or neurosurgical injuries. The
      general surgeons assessed 10/43 potential trauma call patients, and abdominal
      injury was excluded in five (one by clinical examination and four following CT).
      CONCLUSION: A&E staff managed most trauma calls. Most patients did not require
      general surgical intervention. For penetrating injuries, presence of a general
      surgeon remained crucial. For blunt injuries CT was an important adjunct. These
      data suggest that general surgeons do not routinely have to attend all trauma
      calls but can be called if abdominal and/or vascular injuries are specifically
      suspected.

PMID- 15843702
TI  - Flucloxacillin alone or combined with benzylpenicillin to treat lower limb
      cellulitis: a randomised controlled trial.
AB  - OBJECTIVE: To determine whether using intravenous benzylpenicillin in addition to
      intravenous flucloxacillin would result in a more rapid clinical response in
      patients with lower limb cellulitis. METHODS: This was a randomised controlled
      trial set in an inner city teaching hospital, comprising 81 patients with lower
      limb cellulitis requiring intravenous antibiotics. The main outcome measure was
      the mean number of doses of antibiotic required until clinical response. RESULTS:
      The mean number of doses required was 8.47 (95% confidence interval (CI) 7.09 to
      9.86) in the benzylpenicillin and flucloxacillin combined group. In the
      flucloxacillin only group it was 8.71 doses (95% CI 6.90 to 10.5), a mean
      difference of -0.24 doses (95% CI -2.48 to 2.01, p = 0.83). Other markers of
      treatment efficacy showed no difference between groups at review the following
      day; temperature decrease (mean difference -0.07 degrees C, 95% CI -0.76 to 0.62,
      p = 0.84), or diameter decrease of affected area (mean difference -34 mm, 95% CI 
      99 to 31, p = 0.30). Patient subjective assessments were also similar between the
      different drug regimen; improvement on a visual analogue scale of pain/discomfort
      from admission to first review (mean difference 10 mm, 95% CI -12.6 to 14.2, p =
      0.91) and on second review (mean difference 15 mm, 95% CI -18.6 to 21.6, p =
      0.88). Patient overall subjective feelings of improvement on first review (p =
      0.32) and on second review (p = 0.64) were also similar. CONCLUSIONS: This study
      provides no evidence to support the addition of intravenous benzylpenicillin to
      intravenous flucloxacillin in the treatment of lower limb cellulitis.

PMID- 15843703
TI  - Impact of the Department of Health initiative to equip and train acute trusts to
      manage chemically contaminated casualties.
AB  - BACKGROUND: Before 1999, there was no national model or standard doctrine for
      managing casualties from chemical incidents in the UK. A Department of Health
      (DoH) initiative to prepare the National Health Service (NHS) for chemical
      incidents was launched in the same year. This led to the distribution of an NHS
      standard chemical personal protective equipment suit (CPPE) together with a new
      single half day training package (Structured Approach to Chemical Casualties
      (SACC)) in 2001. OBJECTIVES: To assess the impact of the DoH initiative on acute
      hospital and ambulance trusts. To identify deficiencies in the design and
      operational deployment of the new CPPE, training initiative, and decontamination
      procedures at hospital level. METHOD: A survey to assess progress in specific
      areas of chemical incident preparedness and two simulated incidents with "live"
      chemically contaminated casualties conducted in two acute trusts. Umpires
      evaluated the operational performance against DoH SACC standards. RESULTS: There
      has been marked improvement in many aspects of preparedness for chemical
      incidents since the original National Focus survey. Some deficiencies remain and
      this study identified areas for further work. In the live casualty exercises,
      hospital staff complied well with SACC protocols. Some practical difficulties
      were encountered with the deployment of the CPPE and in some aspects of the
      operational response, leading to some delays in the delivery of care to the
      casualties and to the integrity of the uncontaminated (clean) zones within the
      hospitals. CONCLUSION: Problems with the design and deployment of the CPPE,
      together with training difficulties have been fed back into the planning and
      development process.

PMID- 15843704
TI  - Access block causes emergency department overcrowding and ambulance diversion in
      Perth, Western Australia.
AB  - OBJECTIVE: Access block refers to the situation where patients in the emergency
      department (ED) requiring inpatient care are unable to gain access to appropriate
      hospital beds within a reasonable time frame. We systematically evaluated the
      relationship between access block, ED overcrowding, ambulance diversion, and ED
      activity. METHODS: This was a retrospective analysis of data from the Emergency
      Department Information System for the three major central metropolitan EDs in
      Perth, Western Australia, for the calendar years 2001-2. Bivariate analyses were
      performed in order to study the relationship between a range of emergency
      department workload variables, including access block (>8 hour total ED stay for
      admitted patients), ambulance diversion, ED overcrowding, and ED waiting times.
      RESULTS: We studied 259,580 ED attendances. Total diversion hours increased 74%
      from 3.39 hours/day in 2001 to 5.90 hours/day in 2002. ED overcrowding (r = 0.96;
      95% confidence interval (CI) 0.91 to 0.98), ambulance diversion (r = 0.75; 95% CI
      0.49 to 0.88), and ED waiting times for care (r = 0.83; 95% CI 0.65 to 0.93) were
      strongly correlated with high levels of ED occupancy by access blocked patients.
      Total attendances, admissions, discharges, and low acuity patient attendances
      were not associated with ambulance diversion. CONCLUSION: Reducing access block
      should be the highest priority in allocating resources to reduce ED overcrowding.
      This would result in reduced overcrowding, reduced ambulance diversion, and
      improved ED waiting times. Improving hospital inpatient flow, which would
      directly reduce access block, is most likely to achieve this.

PMID- 15843705
TI  - Referral patterns: an audit into referral practice among doctors in emergency
      medicine.
AB  - OBJECTIVES: To develop a standard for safe patient referral from emergency
      medicine (EM) staff to hospital inpatient specialities; to audit adherence to
      that standard, and from this audit, to identify potential risk areas in this
      aspect of patient care; to make recommendations for reducing such risks; and to
      implement those recommendations. METHOD: A standard was introduced and practice
      was compared to that standard using a telephone questionnaire. RESULTS: Many
      problems arising at referral were identified. From these, recommendations were
      made for improvements. At the base hospital, those recommendations were
      implemented. These potential pitfalls are highlighted, together with strategies
      for improving safe handover of patient care. The discussion includes a review of
      the literature on safe handovers, which underpins both the importance of this
      subject and our findings and recommendations. CONCLUSIONS: Referral is an
      important skill for many doctors, particularly those in EM. It requires teaching
      and practice. The corollary to this is that education in this arena is also
      essential for those receiving referrals, to ensure smooth communication and safe
      systems of handover for patients.

PMID- 15843706
TI  - Respiratory and gastrointestinal complications of caustic ingestion in children.
AB  - OBJECTIVES: To determine circumstances surrounding the ingestion of caustic
      substances, the incidence of respiratory and gastrointestinal symptoms at
      presentation, and the degree of investigation and active treatment during
      hospitalisation. Long term respiratory and gastrointestinal sequelae were also
      studied. DESIGN: Retrospective case note study covering a 10 year period.
      SETTING: Tertiary children's hospital. PATIENTS: Children and adolescents
      presenting following caustic ingestions to the Royal Children's Hospital,
      Melbourne. MAIN OUTCOME MEASURES: Requirement for interventional
      oesophagoscopy/bronchoscopy, respiratory support or admission to intensive care,
      and long term gastrointestinal or respiratory sequelae noted. RESULTS: Thirty two
      cases of caustic ingestion were identified in 31 patients (median age 2.6 years;
      78% boys). The average time in hospital was 2 days. Two patients (6%) required
      intensive care nursing, and both required intubation with mechanical ventilation
      (average 33 hours). Thirty patients (97%) underwent diagnostic oesophagoscopy,
      and two underwent laryngoscopy or bronchoscopy for visualisation of the upper
      airway. No patient had long term respiratory consequences. Two patients (6%)
      sustained significant oesophageal injuries requiring interventional
      oesophagoscopy. CONCLUSIONS: Caustic ingestion is overrepresented in boys. Most
      ingestions involve household cleaning products. Symptoms on admission do not
      usually require intensive care admission. Gastrointestinal symptoms predominate
      at presentation, however, these are usually mild. Respiratory symptoms are
      uncommon and respiratory involvement requiring intervention is rare, although the
      presence of respiratory symptoms should be viewed as potentially serious. Long
      term sequelae of caustic ingestion are rare and in this series only affected the
      gastrointestinal tract. The indications for diagnostic endoscopy need further
      evaluation.

PMID- 15843707
TI  - Best evidence topic report. Buccal midazolam as an alternative to rectal diazepam
      for prolonged seizures in childhood and adolescence.
AB  - A short cut review was carried out to establish whether buccal midazolam is
      better than rectal diazepam for treating prolonged seizures in childhood and
      adolescence. Eight papers were found using the reported search, of which two
      presented the best evidence to answer the clinical question. The author, date and
      country of publication, patient group studied, study type, relevant outcomes,
      results, and study weaknesses of these best papers are tabulated. A clinical
      bottom line is stated.

PMID- 15843709
TI  - Best evidence topic report. Aspirin in the treatment of acute pulmonary embolism.
AB  - A short cut review was carried out to establish whether aspirin is a useful
      adjunct in the treatment of acute pulmonary embolism. No papers were found using
      the reported search to answer the clinical question. A clinical bottom line is
      stated.

PMID- 15843710
TI  - Best evidence topic report. Nebulised levalbuterol or albuterol for lowering
      serum potassium.
AB  - A short cut review was carried out to establish whether nebulised levalbuterol is
      better than or equivalent to albuterol for lowering serum potassium. Seven papers
      were found using the reported search, of which three presented the best evidence
      to answer the clinical question. The author, date and country of publication,
      patient group studied, study type, relevant outcomes, results and study
      weaknesses of these best papers are tabulated. A clinical bottom line is stated.

PMID- 15843711
TI  - Best evidence topic report. Bone injection gun placement of intraosseous needles.
AB  - A short cut review was carried out to establish whether the Bone Injection Gun is
      better than a standard intraosseous (IO) needle at obtaining IO access. A total
      of 129 papers were found using the reported search, of which three represent the
      best evidence to answer the clinical question. The author, date and country of
      publication, patient group studied, study type, relevant outcomes, results and
      study weaknesses of these best papers are tabulated. A clinical bottom line is
      stated.

PMID- 15843712
TI  - SOCRATES 7 (synopsis of Cochrane Reviews applicable to emergency services).

PMID- 15843713
TI  - 13 emergency problems in older people.

PMID- 15843714
TI  - Contemporary UK paramedical training and education. How do we train? How should
      we educate?
AB  - OBJECTIVE: To develop an understanding of the current system and future
      development of training and education within a large UK ambulance trust, based
      upon the experiences, beliefs, and opinions of stakeholders. METHODS: This was a
      qualitative naturalistic inquiry using an interpretative constructivist approach
      for 44 interviews with a range of ambulance staff. Stakeholder views on training
      and education were analysed and compared using the constant comparison method.
      RESULTS: Key emergent themes included: issues around prescribed programme entry
      levels and methods; the desire for a higher education curriculum with a balance
      between theory and practice; valid and reliable assessment methods; development
      of a supportive mentorship framework; an emphasis on self directed professional
      development with a focus on deskilling issues; and development of
      interprofessional collaborative links. CONCLUSION: This thematic review suggests
      that this UK ambulance service is in a transition stage, with significant
      organisational, professional, and cultural challenges. The dichotomies,
      boundaries, and development issues are part of the development of an emerging
      profession for which it is essential that the educational agenda is addressed.

PMID- 15843716
TI  - Reversible acute myocardial injury following air bag deployment.
AB  - This case report is about a 62 year old woman who was involved in an accident
      while driving her car, during which the driver side air bag deployed. She
      experienced intense anterior chest pain that radiated to her left arm after the
      accident, but was otherwise well; there was no significant medical history. An
      electrocardiogram done one and half hours after admission revealed 1 mm ST
      segment elevation in leads V2 and V3 and troponin 1 level was raised. She
      underwent cardiac catheterisation but three months after the accident both ECG
      and echocardiographic studies were normal. It is suggested that she underwent
      cardiac contusion rather than a myocardial infarction.

PMID- 15843717
TI  - The reawakening of a sleeping little giant.
AB  - This case report and literature review highlights the classical signs and
      symptoms of herpes zoster infection involving the trigeminal nerve. Incorrect
      diagnosis leads to delay in providing effective treatment and could result in
      failure to identify potentially hazardous ocular complications and to prevent
      chronic post-herpetic pain.

PMID- 15843718
TI  - A role for video assisted thoracoscopy in stable penetrating chest trauma.

PMID- 15843719
TI  - Spontaneous spinal epidural haematoma: a therapeutical challenge? Report of an
      unusual case.
AB  - We report the conservative treatment of a spontaneous spinal epidural haematoma
      attending with acute extensive neurological deficits, which resolved
      spontaneously. Spontaneous remission of spontaneous spinal epidural haematoma
      with severe neurological deficit is rare in the literature. An 80 year old man
      was admitted to our hospital presenting sciatica followed by rapid development of
      paraparesis and cauda equina syndrome, which represents a neurosurgical
      emergency. Magnetic resonance imaging revealed a multilevel epidural haematoma
      from L1 to L5. During the initial diagnostic procedure the symptoms started to
      decline unexpectedly, so the surgical intervention could be withdrawn. Twenty
      four hours after admission the patient was almost free of symptoms, mobile, and
      continent. Awareness and high index of suspicion, and a willingness to seek the
      prompt help of the imaging department, are crucial to successful management
      before the opportunity to treat is lost.

PMID- 15843720
TI  - Acute cyanide poisoning by subcutaneous injection.
AB  - A 30 year old woman with a history of depression and previous suicide attempts
      was brought to the emergency department in coma. She had injected herself with
      cyanide subcutaneously and had severe metabolic acidosis. She underwent sustained
      haemodialysis in the intensive care unit (ICU) before laboratory confirmation of
      cyanide poisoning. The serum cyanide concentration was 4.6 microg/ml. After 48
      hours the patient, now asymptomatic, was discharged from the ICU.

PMID- 15843721
TI  - Survey of blood gas interpretation.

PMID- 15843722
TI  - Glucagon use in beta blocker overdose.

PMID- 15843723
TI  - Emergency rooms differ in the detail.

PMID- 15843724
TI  - Is morphine indicated in acute pulmonary oedema.

PMID- 15843725
TI  - Wobbled splatting--a fast perspective volume rendering method for simulation of x
      ray images from CT.
AB  - 3D/2D registration, the automatic assignment of a global rigid-body
      transformation matching the coordinate systems of patient and preoperative volume
      scan using projection images, is an important topic in image-guided therapy and
      radiation oncology. A crucial part of most 3D/2D registration algorithms is the
      fast computation of digitally rendered radiographs (DRRs) to be compared
      iteratively to radiographs or portal images. Since registration is an iterative
      process, fast generation of DRRs-which are perspective summed voxel renderings-is
      desired. In this note, we present a simple and rapid method for generation of
      DRRs based on splat rendering. As opposed to conventional splatting, antialiasing
      of the resulting images is not achieved by means of computing a discrete point
      spread function (a so-called footprint), but by stochastic distortion of either
      the voxel positions in the volume scan or by the simulation of a focal spot of
      the x-ray tube with non-zero diameter. Our method generates slightly blurred DRRs
      suitable for registration purposes at framerates of approximately 10 Hz when
      rendering volume images with a size of 30 MB.

PMID- 15843726
TI  - The use of the Levenberg-Marquardt curve-fitting algorithm in pharmacokinetic
      modelling of DCE-MRI data.
AB  - The use of curve-fitting and compartmental modelling for calculating
      physiological parameters from measured data has increased in popularity in recent
      years. Finding the 'best fit' of a model to data involves the minimization of a
      merit function. An example of a merit function is the sum of the squares of the
      differences between the data points and the model estimated points. This is
      facilitated by curve-fitting algorithms. Two curve-fitting methods, Levenberg
      Marquardt and MINPACK-1, are investigated with respect to the search start points
      that they require and the accuracy of the returned fits. We have simulated one
      million dynamic contrast enhanced MRI curves using a range of parameters and
      investigated the use of single and multiple search starting points. We found that
      both algorithms, when used with a single starting point, return unreliable fits.
      When multiple start points are used, we found that both algorithms returned
      reliable parameters. However the MINPACK-1 method generally outperformed the
      Levenberg-Marquardt method. We conclude that the use of a single starting point
      when fitting compartmental modelling data such as this produces unsafe results
      and we recommend the use of multiple start points in order to find the global
      minima.

PMID- 15843727
TI  - Cell-phone interference with pocket dosimeters.
AB  - Accurate reporting of personal dose is required by regulation for hospital
      personnel that work with radioactive material. Pocket dosimeters are commonly
      used for monitoring this personal dose. We show that operating a cell phone in
      the vicinity of a pocket dosimeter can introduce large and erroneous readings of
      the dosimeter. This note reports a systematic study of this electromagnetic
      interference. We found that simple practical measures are enough to mitigate this
      problem, such as increasing the distance between the cell phone and the dosimeter
      or shielding the dosimeter, while maintaining its sensitivity to ionizing
      radiation, by placing it inside a common anti-static bag.

PMID- 15843728
TI  - Depth-resolved phase retardation measurements for laser-assisted non-ablative
      cartilage reshaping.
AB  - Since polarization-sensitive optical coherence tomography (PS-OCT) is emerging as
      a new technique for determining phase retardation in biological materials, we
      measured phase retardation changes in cartilage during local laser heating for
      application to laser-assisted cartilage reshaping. Thermally-induced changes in
      phase retardation of nasal septal cartilage following Nd:YAG laser irradiation
      were investigated using a PS-OCT system. A PS-OCT system and infrared imaging
      radiometer were used to record, respectively, depth-resolved images of the Stokes
      parameters of light backscattered from ex vivo porcine nasal septal cartilage and
      radiometric temperature changes following laser irradiation. PS-OCT images of
      cartilage were recorded before (control), during and after laser irradiation.
      From the measured Stokes parameters (I, Q, U and V), an estimate of the relative
      phase retardation between two orthogonal polarizations was computed to determine
      birefringence in cartilage. Phase retardation images of light backscattered from
      cartilage show significant changes in retardation following laser irradiation. To
      investigate the origin of retardation changes in response to local heat
      generation, we differentiated two possible mechanisms: dehydration and thermal
      denaturation. PS-OCT images of cartilage were recorded after dehydration in
      glycerol and thermal denaturation in heated physiological saline. In our
      experiments, observed retardation changes in cartilage are primarily due to
      dehydration. Since dehydration is a principal source for retardation changes in
      cartilage over the range of heating profiles investigated, our studies suggest
      that the use of PS-OCT as a feedback control methodology for non-ablative
      cartilage reshaping requires further investigation.

PMID- 15843729
TI  - Physiological effects of indomethacin and celecobix: an S-transform laser Doppler
      flowmetry signal analysis.
AB  - Conventional signal processing typically involves frequency selective techniques
      which are highly inadequate for nonstationary signals. In this paper, we present
      an approach to perform time-frequency selective processing of laser Doppler
      flowmetry (LDF) signals using the S-transform. The approach is motivated by the
      excellent localization, in both time and frequency, afforded by the wavelet basis
      functions. Suitably chosen Gaussian wavelet functions are used to characterize
      the subspace of signals that have a given localized time-frequency support, thus
      enabling a time-frequency partitioning of signals. In this paper, the goal is to
      study the influence of various pharmacological substances taken by the oral way
      (celecobix (Celebrex), indomethacin (Indocid) and placebo) on the physiological
      activity behaviour. The results show that no statistical differences are observed
      in the energy computed from the time-frequency representation of LDF signals, for
      the myogenic, neurogenic and endothelial related metabolic activities between
      Celebrex and placebo, and Indocid and placebo. The work therefore proves that
      these drugs do not affect these physiological activities. For future
      physiological studies, there will therefore be no need to exclude patients having
      taken cyclo-oxygenase 1 inhibitions.

PMID- 15843730
TI  - Comparison of dosimetric standards of USA and France for HDR brachytherapy.
AB  - A bilateral comparison of national dosimetric standards for high dose rate
      brachytherapy has been conducted between the Laboratoire National Henri Becquerel
      and the University of Wisconsin Accredited Dosimetry Calibration Laboratory. A
      complete overview of the methods that are currently in use to establish the two
      national standards is given. The comparison has been carried out using well-type
      transfer ionization chambers. Three units have been calibrated in both
      laboratories, and calibration coefficients have been compared. The discrepancies
      between the two measurements are within 0.3%.

PMID- 15843731
TI  - Three-dimensional dose verification of the clinical application of gamma knife
      stereotactic radiosurgery using polymer gel and MRI.
AB  - This work seeks to verify multi-shot clinical applications of stereotactic
      radiosurgery with a Leksell Gamma Knife model C unit employing a polymer gel-MRI
      based experimental procedure, which has already been shown to be capable of
      verifying the precision and accuracy of dose delivery in single-shot gamma knife
      applications. The treatment plan studied in the present work resembles a clinical
      treatment case of pituitary adenoma using four 8 mm and one 14 mm collimator
      helmet shots to deliver a prescription dose of 15 Gy to the 50% isodose line (30
      Gy maximum dose). For the experimental dose verification of the treatment plan,
      the same criteria as those used in the clinical treatment planning evaluation
      were employed. These included comparison of measured and GammaPlan calculated
      data, in terms of percentage isodose contours on axial, coronal and sagittal
      planes, as well as 3D plan evaluation criteria such as dose-volume histograms for
      the target volume, target coverage and conformity indices. Measured percentage
      isodose contours compared favourably with calculated ones despite individual
      point fluctuations at low dose contours (e.g., 20%) mainly due to the effect of
      T2 measurement uncertainty on dose resolution. Dose-volume histogram data were
      also found in a good agreement while the experimental results for the percentage
      target coverage and conformity index were 94% and 1.17 relative to corresponding
      GammaPlan calculations of 96% and 1.12, respectively. Overall, polymer gel
      results verified the planned dose distribution within experimental uncertainties
      and uncertainty related to the digitization process of selected GammaPlan output
      data.

PMID- 15843732
TI  - Dosimetric accuracy of a staged radiosurgery treatment.
AB  - For large cerebral arteriovenous malformations (AVMs), the efficacy of
      radiosurgery is limited since the large doses necessary to produce obliteration
      may increase the risk of radiation necrosis to unacceptable levels. An
      alternative is to stage the radiosurgery procedure over multiple stages (usually
      two), effectively irradiating a smaller volume of the AVM nidus with a
      therapeutic dose during each session. The difference between coordinate systems
      defined by sequential stereotactic frame placements can be represented by a
      translation and a rotation. A unique transformation can be determined based on
      the coordinates of several fiducial markers fixed to the skull and imaged in each
      stereotactic coordinate system. Using this transformation matrix, isocentre
      coordinates from the first stage can be displayed in the coordinate system of
      subsequent stages allowing computation of a combined dose distribution covering
      the entire AVM. The accuracy of this approach was tested on an anthropomorphic
      head phantom and was verified dosimetrically. Subtle defects in the phantom were
      used as control points, and 2 mm diameter steel balls attached to the surface
      were used as fiducial markers and reference points. CT images (2 mm thick) were
      acquired. Using a transformation matrix developed with two frame placements, the
      predicted locations of control and reference points had an average error of 0.6
      mm near the fiducial markers and 1.0 mm near the control points. Dose
      distributions in a staged treatment approach were accurately calculated using the
      transformation matrix. This approach is simple, fast and accurate. Errors were
      small and clinically acceptable for Gamma Knife radiosurgery. Accuracy can be
      improved by reducing the CT slice thickness.

PMID- 15843733
TI  - Measurements of primary off-axis ratios in wedged asymmetric photon fields: a
      formalism for dose and monitor unit calculations.
AB  - Asymmetric collimators or heavily blocked fields with physical wedges are still
      encountered in daily practice. In such cases, a reliable dosimetry system is
      necessary to perform manual dose and monitor unit calculations in order to
      independently verify the calculations of commercial treatment planning systems.
      In this work, primary wedged off-axis ratios (POAR(w)s) that account for changes
      in the beam intensity along both the wedge gradient and perpendicular directions
      of the photon field, when asymmetric collimators are applied, were measured
      experimentally at specific depths. The measurements were made in phantom with an
      ion chamber along the wedge gradient and the perpendicular directions under 'good
      geometry' conditions. A consistent formalism was presented that could easily be
      implemented in the clinical environment as an independent verification of the
      calculations by a treatment planning system. The accuracy of the method was found
      to be dependent on the specific wedge used, off-axis distance and depth in the
      phantom. In our study, the accuracy was within 2% in most cases for both
      energies. We concluded that the primary wedged off-axis ratios when used along
      with open symmetric field dosimetric parameters could provide adequate accuracy
      for manual monitor unit calculations.

PMID- 15843734
TI  - IMRT sequencing for a six-bank multi-leaf system.
AB  - In this study, we present a sequencer for delivering step-and-shoot IMRT using a
      six-bank multi-leaf system. Such a system was proposed earlier and combines a
      high-resolution field-shaping ability with a large field size. It consists of
      three layers of two opposing leaf banks with 1 cm leaves. The layers are rotated
      relative to each other at 60 degrees . A low-resolution mode of sequencing is
      achieved by using one layer of leaves as primary MLC, while the other two are
      used to improve back-up collimation. For high-resolution sequencing, an algorithm
      is presented that creates segments shaped by all six banks. Compared to a
      hypothetical mini-MLC with 0.4 cm leaves, a similar performance can be achieved,
      but a trade-off has to be made between accuracy and the number of segments.

PMID- 15843735
TI  - IMRT planning on adaptive volume structures--a decisive reduction in
      computational complexity.
AB  - The objective of radiotherapy planning is to find a compromise between the
      contradictive goals of delivering a sufficiently high dose to the target volume
      while widely sparing critical structures. The search for such a compromise
      requires the computation of several plans, which mathematically means solving
      several optimization problems. In the case of intensity modulated radiotherapy
      (IMRT) these problems are large-scale, hence the accumulated computational
      expense is very high. The adaptive clustering method presented in this paper
      overcomes this difficulty. The main idea is to use a preprocessed hierarchy of
      aggregated dose-volume information as a basis for individually adapted
      approximations of the original optimization problems. This leads to a decisively
      reduced computational expense: numerical experiments on several sets of real
      clinical data typically show computation times decreased by a factor of about 10.
      In contrast to earlier work in this field, this reduction in computational
      complexity will not lead to a loss in accuracy: the adaptive clustering method
      produces the optimum of the original optimization problem.

PMID- 15843736
TI  - Experimental verification of lung dose with radiochromic film: comparison with
      Monte Carlo simulations and commercially available treatment planning systems.
AB  - The purpose of this study was to assess the absorbed dose in and around lung
      tissue by performing radiochromic film measurements, Monte Carlo simulations and
      calculations with superposition convolution algorithms. We considered a layered
      polystyrene phantom of 12 x 12 x 12 cm3 containing a central cavity of 6 x 6 x 6
      cm3 filled with Gammex RMI lung-equivalent material. Two field configurations
      were investigated, a small 1 x 10 cm2 field and a larger 10 x 10 cm2 field.
      First, we performed Monte Carlo simulations to investigate the influence of
      radiochromic film itself on the measured dose distribution when the film
      intersects a lung-equivalent region and is oriented parallel to the central beam
      axis. To that end, the film and the lung-equivalent materials were modelled in
      detail, taking into account their specific composition. Next, measurements were
      performed with the film oriented both parallel and perpendicular to the central
      beam axis to verify the results of our Monte Carlo simulations. Finally, we
      digitized the phantom in two commercially available treatment planning systems,
      Helax-TMS version 6.1A and Pinnacle version 6.2b, and calculated the absorbed
      dose in the phantom with their incorporated superposition convolution algorithms
      to compare with the Monte Carlo simulations. Comparing Monte Carlo simulations
      with measurements reveals that radiochromic film is a reliable dosimeter in and
      around lung-equivalent regions when the film is positioned perpendicular to the
      central beam axis. Radiochromic film is also able to predict the absorbed dose
      accurately when the film is positioned parallel to the central beam axis through
      the lung-equivalent region. However, attention must be paid when the film is not
      positioned along the central beam axis, in which case the film gradually
      attenuates the beam and decreases the dose measured behind the cavity. This
      underdosage disappears by offsetting the film a few centimetres. We find
      deviations of about 3.6% between Monte Carlo and the superposition convolution
      algorithm of Pinnacle behind the lung region, for both field configurations.
      Pinnacle is quite accurate in the lung region. Deviations up to 5.6% for the
      small field are found in the lung region between Monte Carlo and the
      superposition convolution algorithm of Helax-TMS. Behind the lung region, Helax
      TMS is in better agreement with Monte Carlo. Radiochromic film measurements or
      Monte Carlo simulations are reliable methods to establish the dose in and around
      lung tissue.

PMID- 15843737
TI  - Detection and correction of patient movement in prostate brachytherapy seed
      reconstruction.
AB  - Intraoperative dosimetry of prostate brachytherapy can help optimize the dose
      distribution and potentially improve clinical outcome. Evaluation of dose
      distribution during the seed implant procedure requires the knowledge of 3D seed
      coordinates. Fluoroscopy-based seed localization is a viable option. From three x
      ray projections obtained at different gantry angles, 3D seed positions can be
      determined. However, when local anaesthesia is used for prostate brachytherapy,
      the patient movement during fluoroscopy image capture becomes a practical
      problem. If uncorrected, the errors introduced by patient motion between image
      captures would cause seed mismatches. Subsequently, the seed reconstruction
      algorithm would either fail to reconstruct or yield erroneous results. We have
      developed an algorithm that permits detection and correction of patient movement
      that may occur between fluoroscopy image captures. The patient movement is
      decomposed into translational shifts along the tabletop and rotation about an
      axis perpendicular to the tabletop. The property of spatial invariance of the co
      planar imaging geometry is used for lateral movement correction. Cranio-caudal
      movement is corrected by analysing the perspective invariance along the x-ray
      axis. Rotation is estimated by an iterative method. The method can detect and
      correct for the range of patient movement commonly seen in the clinical
      environment. The algorithm has been implemented for routine clinical use as the
      preprocessing step for seed reconstruction.

PMID- 15843738
TI  - Stability of miniature electromagnetic tracking systems.
AB  - This study aims at a comparative evaluation of two recently introduced
      electromagnetic tracking systems under reproducible simulated operating-room (OR)
      conditions: the recently launched Medtronic StealthStation, Treon-EM and the NDI
      Aurora. We investigate if and to what extent these systems provide improved
      performance and stability in the presence of surgical instruments as possible
      sources of distortions compared with earlier reports on electromagnetic tracking
      technology. To investigate possible distortions under pseudo-realistic OR
      conditions, a large Langenbeck hook, a dental drill with its handle and an
      ultrasonic (US) scanhead are fixed on a special measurement rack at variable
      distances from the navigation sensor. The position measurements made by the Treon
      EM were least affected by the presence of the instruments. The lengths of the
      mean deviation vectors were 0.21 mm for the Langenbeck hook, 0.23 mm for the
      drill with handle and 0.56 mm for the US scanhead. The Aurora was influenced by
      the three sources of distortion to a higher degree. A mean deviation vector of
      1.44 mm length was observed in the vicinity of the Langenbeck hook, 0.53 mm
      length with the drill and 2.37 mm due to the US scanhead. The maximum of the root
      mean squared error (RMSE) for all coordinates in the presence of the Langenbeck
      hook was 0.3 mm for the Treon and 2.1 mm for the Aurora; the drill caused a
      maximum RMSE of 0.2 mm with the Treon and 1.2 mm with the Aurora. In the presence
      of the US scanhead, the maximum RMSE was 1.4 mm for the Treon and 5.1 mm for the
      Aurora. The new generation of electromagnetic tracking systems has significantly
      improved compared to common systems that were available in the middle of the
      1990s and has reached a high level of technical development. We conclude that, in
      general, both systems are suitable for routine clinical application.

PMID- 15843739
TI  - A backprojection-filtration algorithm for nonstandard spiral cone-beam CT with an
      n-PI-window.
AB  - For applications in bolus-chasing computed tomography (CT) angiography and
      electron-beam micro-CT, the backprojection-filtration (BPF) formula developed by
      Zou and Pan was recently generalized by Ye et al to reconstruct images from cone
      beam data collected along a rather flexible scanning locus, including a
      nonstandard spiral. A major implication of the generalized BPF formula is that it
      can be applied for n-PI-window-based reconstruction in the nonstandard spiral
      scanning case. In this paper, we design an n-PI-window-based BPF algorithm, and
      report the numerical simulation results with the 3D Shepp-Logan phantom and
      Defrise disk phantom. The proposed BPF algorithm consists of three steps: cone
      beam data differentiation, weighted backprojection and inverse Hilbert
      filtration. Our simulated results demonstrate the feasibility and merits of the
      proposed algorithm.

PMID- 15843740
TI  - Optimization of the accuracy of retention and washout measurements of 99mTc
      Sestamibi from breast tumours using an anthropomorphic phantom.
AB  - Quantifying the retention or washout of (99m)Tc-Sestamibi (MIBI) in breast
      tumours in vivo may provide a basis for predicting the chemotherapy response. The
      aim of this study is to investigate the variations and limitations of the
      different methods used to quantify these parameters. A phantom was developed that
      allowed the modelling of MIBI pharmacokinetics in both the breast tumour and
      normal breast tissue. Washout and retention were calculated from tumour uptake
      values based on (1) background corrected counts or (2) total counts in the tumour
      region of interest (ROI), or (3) tumour to background ratios (TBR), or (4)
      normalized TBR (nTBR). Method 1 was the most accurate method of quantification
      whilst method 3 was the most inaccurate. The accuracy of method 1 was independent
      of the times at which images were acquired, but three sources of error are
      identified involving incorrect background selection, ROI reproducibility and
      inconsistent temporal separation of images. In conclusion, background subtracted
      tumour counts should be used in the calculation of MIBI retention or washout.
      Accurate results are dependent on selecting the appropriate background, drawing
      consistent ROIs and using reproducible time intervals between images.

PMID- 15843741
TI  - Pharmaco-thermodynamics of deuterium-induced oedema in living rat brain via 1H2O
      MRI: implications for boron neutron capture therapy of malignant brain tumours.
AB  - In addition to its common usage as a tracer in metabolic and physiological
      studies, deuterium possesses anti-tumoural activity and confers protection
      against gamma-irradiation. A more recent interest in deuterium emanates from the
      search for alternatives capable of improving neutron penetrance whilst reducing
      healthy tissue radiation dose deposition in boron neutron capture therapy of
      malignant brain tumours. Despite this potential clinical application, deuterium
      induces brain oedema, which is detrimental to neutron capture therapy. In this
      study, five adult male rats were titrated with deuterated drinking water while
      brain oedema was monitored via water proton magnetic resonance imaging. This
      report concludes that deuterium, as well as deuterium-induced brain oedema,
      possesses a uniform brain bio-distribution. At a steady-state blood fluid
      deuteration value of 16%, when the deuterium isotope fraction in drinking water
      was 25%, a mean oedematous volume change of 9 +/- 2% (p-value <0.001) was
      observed in the rat brain-this may account for neurological and behavioural
      abnormalities found in mammals drinking highly deuterated water. In addition to
      characterizing the pharmaco-thermodynamics of deuterium-induced oedema, this
      report also estimates the impact of oedema on thermal neutron enhancement and
      effective dose reduction factors using simple linear transport calculations.
      While body fluid deuteration enhances thermal neutron flux penetrance and reduces
      dose deposition, oedema has the opposite effect because it increases the volume
      of interest, e.g., the brain volume. Thermal neutron enhancement and effective
      dose reduction factors could be reduced by as much as approximately 10% in the
      presence of a 9% water volume increase (oedema).

PMID- 15843742
TI  - Ellipsoidal head model for fetal magnetoencephalography: forward and inverse
      solutions.
AB  - Fetal magnetoencephalography (fMEG) is a non-invasive technique where
      measurements of the magnetic field outside the maternal abdomen are used to infer
      the source location and signals of the fetus' neural activity. There are a number
      of aspects related to fMEG modelling that must be addressed, such as the
      conductor volume, fetal position and orientation, gestation period, etc. We
      propose a solution to the forward problem of fMEG based on an ellipsoidal head
      geometry. This model has the advantage of highlighting special characteristics of
      the field that are inherent to the anisotropy of the human head, such as the
      spread and orientation of the field in relationship with the localization and
      position of the fetal head. Our forward solution is presented in the form of a
      kernel matrix that facilitates the solution of the inverse problem through
      decoupling of the dipole localization parameters from the source signals. Then,
      we use this model and the maximum likelihood technique to solve the inverse
      problem assuming the availability of measurements from multiple trials. The
      applicability and performance of our methods are illustrated through numerical
      examples based on a real 151-channel SQUID fMEG measurement system (SARA). SARA
      is an MEG system especially designed for fetal assessment and is currently used
      for heart and brain studies. Finally, since our model requires knowledge of the
      best-fitting ellipsoid's centre location and semiaxes lengths, we propose a
      method for estimating these parameters through a least-squares fit on anatomical
      information obtained from three-dimensional ultrasound images.

PMID- 15843743
TI  - Perturbation model for light propagation through diffusive layered media.
AB  - A fast and novel perturbation approach is proposed to account for the effects of
      absorbing inhomogeneities on light propagation through layered media. The
      calculation has been implemented with the Born approximation. Examples of results
      are reported both for a two- and for a three-layered medium. The method presented
      has been validated with the results of Monte Carlo simulations. The forward
      solver presented in this paper can be of significant use in investigating the
      feasibility of real experiments, e.g. for functional imaging studies.

PMID- 15843744
TI  - Theoretical and experimental validation of a dual-frequency excitation method for
      spatial control of cavitation.
AB  - Inertial cavitation has been implicated as the primary mechanism for a host of
      emerging applications. In all these applications, the main concern is to induce
      cavitation in perfectly controlled locations in the field; this means
      specifically to be able to achieve the cavitation threshold at the geometrical
      focus of the transducer without stimulating its near field. In this study, we
      develop dual-frequency methods to preferentially lower the cavitation threshold
      at the focus relative to the rest of the field. Two families of dual-frequency
      driving waveforms are evaluated in a bubble model incorporating rectified
      diffusion. Results are then verified by experiment. Finally, the performance of
      the rest of acoustic field in suppressing cavitation when cavitation is induced
      at the focus is investigated theoretically and checked experimentally. This study
      shows that dual-frequency phased arrays could be used to precisely control
      cavitation. The cavitation threshold is proved to be 1.2 times higher in the near
      field than at the focus. The concept of cavitation field is introduced and
      complements cavitation studies concentrating on the focal behaviour only.

PMID- 15843745
TI  - A predictive mathematical model for the calculation of the final mass of Graves'
      disease thyroids treated with 131I.
AB  - Substantial reductions in thyroid volume (up to 70-80%) after radioiodine therapy
      of Graves' hyperthyroidism are common and have been reported in the literature. A
      relationship between thyroid volume reduction and outcome of 131I therapy of
      Graves' disease has been reported by some authors. This important result could be
      used to decide individually the optimal radioiodine activity A0 (MBq) to
      administer to the patient, but a predictive model relating the change in gland
      volume to A0 is required. Recently, a mathematical model of thyroid mass
      reduction during the clearance phase (30-35 days) after 131I administration to
      patients with Graves' disease has been published and used as the basis for
      prescribing the therapeutic thyroid absorbed dose. It is well known that the
      thyroid volume reduction goes on until 1 year after therapy. In this paper, a
      mathematical model to predict the final mass of Graves' diseased thyroids
      submitted to 131I therapy is presented. This model represents a tentative
      explanation of what occurs macroscopically after the end of the clearance phase
      of radioiodine in the gland (the so-called second-order effects). It is shown
      that the final thyroid mass depends on its basal mass, on the radiation dose
      absorbed by the gland and on a constant value alpha typical of thyroid tissue.
      Alpha has been evaluated based on a set of measurements made in 15 reference
      patients affected by Graves' disease and submitted to 131I therapy. A predictive
      equation for the calculation of the final mass of thyroid is presented. It is
      based on macroscopic parameters measurable after a diagnostic 131I capsule
      administration (0.37-1.85 MBq), before giving the therapy. The final mass
      calculated using this equation is compared to the final mass of thyroid measured
      1 year after therapy administration in 22 Graves' diseased patients. The final
      masses calculated and measured 1 year after therapy are in fairly good agreement
      (R = 0.81). The possibility, for the physician, to decide a therapeutic activity
      based on the desired decrease of thyroid mass instead of on a fixed thyroid
      absorbed dose could be a new opportunity to cure Graves' disease.

PMID- 15843746
TI  - [Amebic colitis presenting with pretibial pitting edema].

PMID- 15843747
TI  - [Hepatocellular carcinoma in Korea: introduction and overview].
AB  - Hepatocellular carcinoma (HCC) is a highly malignant, generally fatal neoplasm
      arising from hepatocytes. HCC accounts for over 80% of all primary liver cancers
      which ranks fourth among the organ-specific causes of cancer-related deaths
      worldwide. HCC is particularly prevalent in Korea where the age standardized
      incidence rate is 46.5 per 100,000 population. Infection with hepatitis B virus
      (HBV) or hepatitis C virus (HCV) or presence of liver cirrhosis are important
      risk factors for HCC development globally. Infection with HBV is the most
      important risk for HCC in Asia except Japan. The high incidence rate of HCC in
      Korea is thought to be related to the high carrier rate (5-6%) of HBV, which is
      currently being fought via a nationwide vaccination program. Although progress
      has been made in the management of HCC including chemoembolization and local
      ablation therapy, there has been little overall reduction in HCC mortality during
      the past 20 years. Recently, five year survival rate of primary liver cancer is
      9.6% in Korea. Such poor prognosis of HCC results from the late detection of
      cancer, an aggressive tumor biology and underlying chronic liver diseases. Only a
      limited proportion of patients are candidates for potentially curative forms of
      treatment. Therefore efforts should be directed toward an effective surveillance
      program. The early detection of HCC is the important approach in reducing HCC
      mortality in the short term. Because almost eighty percent of HCC is diagnosed in
      late stage, we launched a nationwide surveillance program to screen high risk
      groups (HBV or HCV carriers or liver cirrhosis, over 40 years old) and formulated
      the Korean practice guideline for the diagnosis and treatment of HCC with special
      emphasis on advanced stage of HCC.

PMID- 15843748
TI  - [Pathology of hepatocellular carcinoma: recent update].
AB  - In recent years, growing number of literatures have supported the concept that
      large nodules usually found in cirrhotic livers represent premalignant lesions in
      the setting of chronic liver disease. With the use of advanced imaging
      techniques, nodules suspicious for malignancy have often been identified and
      resected. While some resected lesions were found to be small hepatocellular
      carcinomas (HCCs), others were not. Some of these non-malignant nodules were
      devoid of atypia, some had architectural or cytological atypia insufficient for a
      diagnosis of HCC though they are suggestive of a premalignant state, while others
      contained microscopic subnodules of HCC. In follow-up studies and series of
      explants from liver transplant centers, the occasional finding of microscopic
      foci of HCC in the nodules was confirmed and significant associations with HCC
      elsewhere in the same liver were established. Such findings suggested that these
      nodular lesions, which are referred as "dysplastic nodules" (or adenomatous
      hyperplasia), are probably a frequent pathway in human hepatocarcinogenesis. We
      discuss the pathological characteristics of dysplastic nodules and small HCCs.

PMID- 15843749
TI  - [Imaging diagnosis of hepatocellular carcinoma].
AB  - In patients with chronic liver disease, hepatocellular carcinomas are developed
      from regenerative nodule via dysplastic nodule and early hepatocellular carcinoma
      to advanced hepatocellular carcinoma during multistep hepatocarcinogenesis. In
      this article, imaging findings of various imaging modalities are described
      pertaining to the above mentioned hepatocellular nodules occurring in the
      cirrhotic liver, correlating with pathologic findings.

PMID- 15843750
TI  - [Surgical treatment of hepatocellular carcinoma].
AB  - Due to recent rapid advances in imaging modalities, there has been a marked
      increase in the early diagnosis of hepatocellular carcinoma (HCC). Also, the
      emergence of effective local treatment methods has lead to the necessity for a
      wider selection of therapeutic modalities depending on the individual
      characteristics of each patient, such as tumor factors and hepatic factors,
      rather than a single uniform approach. At present, accurate preoperative liver
      function evaluation is available, and in addition, increased knowledge of the
      liver anatomy through liver transplantation, and advances in postoperative
      patient care has subsequently decreased the morbidity and mortality rates
      significantly after surgery. Such newly developed techniques and acquired
      knowledge has allowed the surgical option to expand from the classical hepatic
      lobectomy to systematic subsegmentectomy. Not only for early HCC, but also for
      intermediate HCC and advanced HCC, hepatectomy has shown the best results in each
      stage of disease with regard to treatment goals. It is therefore thought that
      hepatectomy should always be considered as the main treatment method in the
      multimodality treatment of HCC, as long as the liver function reserve permits, to
      enhance the quality of life, increase survival, and to cure disease. The authors
      present here a summary of the role of surgical approaches in HCC with respect to
      recent increases in the detection of early stage disease, new therapeutic
      modalities, and a new staging system for HCC.

PMID- 15843751
TI  - [Radiological intervention of hepatocellular carcinoma].
AB  - In spite of the nice screening program using the state-of-the-art imaging
      modalities, most patients with hepatocellular carcinoma (HCC) are not eligible
      for curative resection due to poor hepatic functional reserve and multiplicity of
      the tumors. Therefore they greatly rely on percutaneous interventional
      procedures. Among these, transcatheter arterial chemoembolization and local
      ablation therapies including ethanol injection therapy or radiofrequency (RF)
      thermal ablation have gained wider acceptance for the local treatment of
      unresectable HCC with growing evidence of survival gain. Although we need more
      prospective randomized trials to determine the definite role of these
      interventional therapies, the current consensus is that they are safe and
      effective for the local control of small HCC and have a potential to replace
      definitive surgical options. In this review, the basic principles and published
      clinical results including long-term survival rates and complications are
      reviewed. The benefits and limitations of each therapy are also discussed.

PMID- 15843752
TI  - [Experimental treatment of hepatocellular carcinoma].
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies world wide.
      Several experimental treatments have been tested against HCC. Those are
      chemotherapy, high dose proton beam radiotherapy, external beam radiotherapy,
      cyberknife, antibody-directed therapy and immunotherapy. Neither single nor
      combination therapy have demonstrated any clear reproducible benefit in terms of
      overall survival. Tamoxifen and antiandrogen therapy were not effective in
      prolonging survival when tested in randomized controlled trial. The modern
      radiation therapy concept such as intensity-modulated, image-guided, and
      stereotactic body radiation therapy may show promising effects on HCC. The
      increasing promise of targeted drug therapy in cancer needs to be particularly
      pursued in the treatment of HCC, in which cytotoxic agents are not usually
      effective. Other approaches include hormonal manipulation, immunotherapy, and
      specific inhibition of angiogenesis or growth factors. These issues stress the
      need for basic research in carcinogenesis in general and HCC in particular.

PMID- 15843753
TI  - [The inhibitory effect of curcumin on the growth of human colon cancer cells (HT
      29, WiDr) in vitro].
AB  - BACKGROUND/AIMS: The effects of curcumin on the growth of human colon cancer cell
      lines, HT-29 and WiDr cells were examined and the effects of 5-fluorouracil (5
      FU) were also studied. METHODS: The growth of HT-29 and WiDr cells were examined
      by counting cell number on two and four days treatment with 1-40 microm of
      curcumin, and 0.1 microg/mL, 0.3 microg/mL of 5-FU. The reversibility of curcumin
      was examined on one day to seven days treatment with 10 microm curcumin after
      seeding to 2 x 10(4) cells/well. To examine the inhibitory effects of curcumin,
      cell cycle analysis was done on the HT-29 cells after four days treatment with 20
      microm curcumin. RESULTS: Curcumin inhibited the growth of HT-29 and WiDr cells
      in a dose-dependent fashion. The growth rate of the group in which curcumin was
      removed by media change 24 hours after the treatment of curcumin was not
      different from that of control group. Curcumin combined with 5-FU markedly
      inhibited the growth of HT-29 and WiDr cells compared to curcumin or 5-FU alone.
      After four days treatment of HT-29 cells with 20 microm curcumin, the fraction of
      cells in G2-M phase was 35.3% in curcumin group, much higher than 13.8% of the
      control group. CONCLUSIONS: Curcumin significantly inhibited the growth of HT-29
      and WiDr cells in a dose-dependent, reversible fashion.

PMID- 15843754
TI  - [Frequent epigenetic inactivation of XAF1 by promotor hypermethylation in human
      colon cancers].
AB  - BACKGROUND/AIMS: X-linked inhibitor of apoptosis (XIAP) is the most potent member
      of the IAP family that exerts antiapoptotic effects. Recently, XIAP-associated
      factor 1 (XAF1) and two mitochondrial proteins, Smac/ DIABLO and HtrA2, have been
      identified to negatively regulate the caspase-inhibiting activity of XIAP. We
      explored the candidacy of XAF1, Smac/DIABLO and HtrA2 as a tumor suppressor in
      colonic carcinogenesis. METHODS: Expression and mutation status of the genes in
      10 colorectal carcinoma cell lines and 40 primary tumors were examined by
      quantitative PCR analysis. RESULTS: XAF1 transcript was not expressed or present
      at extremely low levels in 60% (6/10) of cancer cell lines whereas Smac/DIABLO
      and HtrA2 are normally expressed in all cell lines examined. Tumor-specific loss
      or reduction of XAF1 was also found in 35% (14/40) of matched tissue sets
      obtained from the same patients. XAF1 transcript was reactivated in all the low
      expressor cell lines by treatment with the demethylating agent 5-aza-2'
      deoxycytidine. Moreover, bisulfite DNA sequencing analysis for 34 CpG sites in
      the promoter region revealed a strong association between hypermethylation and
      gene silencing. Restoration of XAF1 expression resulted in enhanced apoptotic
      response to etoposide and 5-flurouracil, whereas knockdown of XAF1 expression by
      siRNA transfection significantly inhibited chemotherapeutic drug-induced
      apoptosis. CONCLUSIONS: XAF1 undergoes epigenetic gene silencing in a
      considerable proportion of human colon cancers by aberrant promoter
      hypermethylation, suggesting that XAF1 inactivation might be implicated in
      colonic tumorigenesis.

PMID- 15843755
TI  - [The detection of antigenic protein of HCV in gastric mucosa].
AB  - BACKGROUND/AIMS: As a preliminary study to test the possibility of oral
      transmission of hepatitis C virus (HCV), many investigations in order to detect
      the extrahepatic localization of HCV have been performed. In this study, we
      examined the presence of HCV viral proteins in gastric mucosa. METHODS:
      Immunohistochemical staining to NS3 protein were done to detect the HCV virus in
      gastric mucosa. The results were compared with NS5a protein staining to confirm
      the NS3 protein staining. RESULTS: Total of 164 patient were included. 58
      patients with anti-HCV (+) were designated to case group and 70 with anti-HCV (-)
      to control group. 36 were excluded in this study due to concomitant illness. Anti
      HCV (+) group showed 50.0% (29/58) of positivity to NS3 protein staining and anti
      HCV (-) group showed 12.6% (9/70) of positivity (p<0.001). Immunohistochemical
      staining to NS5a protein were done to validate the result of NS3 (+) staining in
      the anti-HCV (+) group (n=58). NS5a (+) staining were observed in 58.6% (34/58).
      The results of NS5a staining were consistent with that of NS3 in 70.7%. The
      reliability coefficients by Chronbach's Alpha for NS3 and NS5a stain test was
      0.59. CONCLUSIONS: HCV can exist in gastric mucosal cell as an extrahepatic
      presence. In the future, this study may provide some fundamental data for the
      research of possible oral transmission route of HCV.

PMID- 15843756
TI  - [A case of pulmonary thromboembolism in active ulcerative colitis].
AB  - Thromboembolic disease is a significant cause of morbidity and mortality in
      patients with inflammatory bowel disease. The reported incidence is 1-6%. The
      most common thromboembolic complications are deep venous thrombosis of legs and
      pulmonary thromboembolism. Cerebral thrombosis, portal vein thrombosis, retinal
      venous thrombosis and arterial thrombosis were also reported. We experienced a
      case of ulcerative colitis complicated with pulmonary thromboembolism. The
      patient was a 70-year-old woman who was diagnosed as ulcerative colitis on
      colonoscopy. We used prednisolone and sulfasalazine for the treatment of
      ulcerative colitis. Twenty five days later, she complained of abrupt dyspnea and
      chest pain. Chest CT and ventilation-perfusion scan revealed a thromboembolism in
      both lung. After the treatment of heparin & warfarin therapy, follow-up chest CT
      showed much regressed pulmonary thromboembolism. We report a 70-year-old woman
      with ulcerative colitis complicated with pulmonary thromboembolism and treated
      with heparin & warfarin therapy successfully.

PMID- 15843758
TI  - Atomoxetine and tics in ADHD.

PMID- 15843759
TI  - Suicidality following black-box warning.

PMID- 15843760
TI  - Cumulative prevalence of psychiatric disorder in youths.

PMID- 15843761
TI  - Panic symptoms without report of anxiety.

PMID- 15843762
TI  - Double-blind 18-month trial of lithium versus divalproex maintenance treatment in
      pediatric bipolar disorder.
AB  - OBJECTIVE: To determine whether divalproex sodium (DVPX) was superior to lithium
      carbonate (Li+) in the maintenance monotherapy treatment of youths diagnosed with
      bipolar disorder who had been previously stabilized on combination Li+ and DVPX
      (Li+/DVPX) pharmacotherapy. METHOD: Youths ages 5-17 years with bipolar I or II
      disorder were initially treated with Li /DVPX. Patients meeting remission
      criteria for four consecutive weeks were then randomized in a double-blind
      fashion to treatment with either Li+ or DVPX for up to 76 weeks. Study
      participation ended if the subject required additional clinical intervention or
      if the subject did not adhere to study procedures. RESULTS: Patients were
      recruited between July 1998 and May 2002. One hundred thirty-nine youths with a
      mean (SD) age of 10.8 (3.5) years were initially treated with Li+/DVPX for a mean
      (SD) duration of 10.7 (5.4) weeks. Sixty youths were then randomized to receive
      monotherapy with Li+ (n = 30) or DVPX (n = 30). The Li+ and DVPX treatment groups
      did not differ in survival time until emerging symptoms of relapse (p = .55) or
      survival time until discontinuation for any reason (p = .72). CONCLUSIONS: DVPX
      was not found to be superior to Li+ as maintenance treatment in youths who
      stabilized on combination Li+/DVPX pharmacotherapy.

PMID- 15843764
TI  - Six-week open-label reboxetine treatment in children and adolescents with
      attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: This open-label study assessed the effectiveness of reboxetine, a
      selective norepinephrine reuptake inhibitor, in children and adolescents with
      attention-deficit/hyperactivity disorder (ADHD) resistant to a previous
      methylphenidate trial. METHOD: Thirty-one child and adolescent outpatients, aged
      8 to 18 (mean age, 11.7; SD = 2.87) years, diagnosed with ADHD were enrolled in a
      6-week open-label study. Assessments included rater-administered scales (DSM-IV
      ADHD Scale; Clinical Global Impressions Scale), parent-administered scales (the
      Abbreviated Conners Rating Scale), and self-administered-scales for the
      evaluation of depressive (Children's Depression Inventory) and anxiety (the
      Revised Children's Manifest Anxiety Scale) symptoms. Reboxetine was initiated and
      maintained at a dose of 4 mg/day. RESULTS: A significant decrease in ADHD
      symptoms, on all scales measured, was noted. Adverse effects were relatively mild
      and transient. The most common adverse effects were drowsiness/sedation and
      gastrointestinal complaints. CONCLUSIONS: The results of the current open-label
      study suggest the effectiveness of reboxetine in the treatment of ADHD in
      methylphenidate-resistant children and adolescents. Double-blind, placebo-, and
      active comparator-controlled studies are indicated to rigorously test the
      efficacy of reboxetine in ADHD.

PMID- 15843763
TI  - Sequential pharmacotherapy for children with comorbid attention
      deficit/hyperactivity and anxiety disorders.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied
      by clinically significant anxiety, but few empirical data guide treatment of
      children meeting full DSM-IV criteria for ADHD and anxiety disorders (ADHD/ANX).
      This study examined the efficacy of sequential pharmacotherapy for ADHD/ANX
      children. METHOD: Children, age 6 to 17 years, with ADHD/ANX were titrated to
      optimal methylphenidate dose and assessed along with children who entered the
      study on a previously optimized stimulant. Children with improved ADHD who
      remained anxious were randomly assigned to 8 weeks of double-blind stimulant +
      fluvoxamine (STIM/FLV) or stimulant + placebo (STIM/PL). Primary efficacy
      measures were the Swanson, Nolan, Atkins, and Pelham IV Parent and Teacher Rating
      Scale ADHD score and the Pediatric Anxiety Rating Scale total score. ADHD, ANX,
      and overall Clinical Global Impressions-Improvement scores were also obtained.
      RESULTS: Of the 32 medication-naive children openly treated with methylphenidate,
      26 (81%) improved as to ADHD. Twenty-five children entered the randomized trial.
      Intent-to-treat analysis indicated no differences between the STIM/FLV (n = 15)
      and STIM/PL groups on the Pediatric Anxiety Rating Scale or Clinical Global
      Impressions-Improvement-defined responder rate. Medications in both arms were
      well tolerated. CONCLUSIONS: Children with ADHD/ANX have a response rate to
      stimulants for ADHD that is comparable with that of children with general ADHD.
      The benefit of adding FLV to stimulants for ANX remains unproven.

PMID- 15843765
TI  - Predictors of personality change due to traumatic brain injury in children and
      adolescents in the first six months after injury.
AB  - OBJECTIVE: To assess the phenomenology and predictive factors of personality
      change due to traumatic brain injury. METHOD: Children (N = 177), aged 5 to 14
      years with traumatic brain injury from consecutive admissions to five trauma
      centers, were followed prospectively at baseline and 6 months with semistructured
      psychiatric interviews. Injury severity, lesion characteristics, and preinjury
      variables including psychiatric disorder, family psychiatric history, family
      function, socioeconomic status, psychosocial adversity, and adaptive function
      were assessed with standardized instruments. RESULTS: Personality change occurred
      in 22% of participants in the first 6 months after injury. Severity of injury
      predicted personality change, whereas none of the psychosocial variables
      predicted personality change. Lesions of the dorsal prefrontal cortex,
      specifically the superior frontal gyrus, were associated with personality change
      after controlling for severity of injury or the presence of other lesions.
      CONCLUSIONS: These findings are consistent with models of affective dysregulation
      that implicate a dorsal prefrontal cortex system important for effortful
      regulation of affective states.

PMID- 15843766
TI  - Prefrontal and executive attention network lesions and the development of
      attention-deficit/hyperactivity symptomatology.
AB  - OBJECTIVE: To investigate the association between focal stroke lesions of
      Posner's executive attention network and a specific region of interest in the
      frontal lobes (orbital frontal and mesial frontal) and either attention
      deficit/hyperactivity disorder (ADHD) or traits of the disorder (ADHD
      symptomatology). METHOD: Twenty-nine children with focal stroke lesions were
      studied with standardized psychiatric assessments and anatomical brain magnetic
      resonance imaging. The pattern of lesion overlap in subjects with ADHD
      symptomatology was determined. RESULTS: Fifteen of 28 subjects with no prestroke
      ADHD were diagnosed with ADHD symptomatology at the time of assessment. The
      extent of lesions within the executive attention network was marginally related
      to ADHD symptomatology (p = .088; effect size = 0.66), whereas the extent of
      lesions in the specific frontal region of interest was significantly related to
      ADHD symptomatology (p = .040; effect size = 0.82). CONCLUSIONS: Lesions within
      Posner's executive attention network and its orbital frontal connections may be
      linked to important mechanisms in the expression of ADHD symptomatology after
      childhood stroke. These findings are consistent with functional and structural
      imaging findings in studies of idiopathic ADHD.

PMID- 15843767
TI  - Motivational effects on motor timing in attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: This study was designed to clarify whether poor performance of
      children with attention-deficit/hyperactivity disorder (ADHD) on motor timing
      tasks reflects a true deficit in the temporal organization of motor output or is
      due to a lack of intrinsic motivation. METHOD: Eighteen children with ADHD (age 8
      12) were compared with 18 age- and gender-matched normal controls with respect to
      timing precision, timing variability, and the frequency of extreme under- and
      overestimations during a 1-second interval production task. Monetary reward,
      response cost, and no reward were implemented to manipulate motivation. RESULTS:
      Children with ADHD produced significantly more inaccurate and more variable time
      intervals and exhibited a larger number of extreme over- and underestimations
      than control children. Although all children performed significantly better when
      monetary incentives were applied, group differences were not eliminated.
      CONCLUSIONS: In this study, no evidence was found for a motivational deficit as
      an explanation for impaired performance on a time production task in ADHD.
      Rather, results provide clear support for a generic motor timing deficit,
      probably due to a dysfunctional frontostriatocerebellar network involved in
      temporal aspects of motor preparation.

PMID- 15843768
TI  - Memory and learning in pediatric bipolar disorder.
AB  - OBJECTIVE: To test the hypothesis that patients with pediatric bipolar disorder
      (PBPD) would demonstrate impairment relative to diagnosis-free controls of
      comparable age, gender, and IQ on measures of memory functioning. METHOD: The
      authors administered a battery of verbal and visuospatial memory tests to 35
      outpatients with PBPD and 20 healthy controls who participated as volunteers in
      this study. Groups did not differ on age, gender, or IQ. RESULTS: Consistent with
      findings in adults with BPD, patients with PBPD performed more poorly than
      controls on measures of verbal learning/memory and delayed facial recognition
      memory. Impaired memory was particularly evident in patients with comorbid
      PBPD/attention-deficit/hyperactivity disorder or acute mood symptoms.
      CONCLUSIONS: These findings suggest that deficits in verbal learning and memory,
      as well as some aspects of visuospatial memory, characterize patients with narrow
      phenotype PBPD. Further research is needed, however, to clarify the roles of
      comorbid attention-deficit/hyperactivity disorder and acute mood state in the
      emergence of these deficits. Given the apparent continuity in memory dysfunction
      between adult BPD and narrow phenotype PBPD, research aimed at elucidating
      underlying neural mechanisms for this set of deficits is warranted.

PMID- 15843769
TI  - Heart rate correlates of attachment status in young mothers and their infants.
AB  - OBJECTIVE: To explore heart rate (HR) correlates of attachment behavior in young
      mothers and their infants to generate specific hypotheses and to provide pilot
      data on which studies to test those hypotheses might be based. METHOD: Using the
      strange situation procedure, patterns of attachment were assessed in 41 low
      income adolescent mothers and their infants. During the procedure, the HRs of the
      infants and mothers were recorded. The HR changes were analyzed and infant
      attachment group differences were examined. RESULTS: Infants in all attachment
      groups demonstrated a similar HR response. There were, however, notably different
      behavioral reactions in the insecure groups: relatively increased behavioral
      distress in the insecure/resistant infants and relatively decreased behavioral
      distress in insecure-avoidant infants. Mothers of insecure-resistant infants
      demonstrated elevated HRs during reunions and the insecure/resistant dyads
      demonstrated lower consistency between HR changes in infant and mother than the
      secure dyads. CONCLUSIONS: The results suggest the discrepancy between attachment
      related behavioral reactions and HR response in insecurely attached infants.
      Maternal and dyadic HR changes vary between the attachment groups.

PMID- 15843770
TI  - Association of the DRD4 exon III polymorphism with smoking in fifteen-year-olds:
      a mediating role for novelty seeking?
AB  - OBJECTIVE: This study was designed to examine the role of DNA variants of the
      dopamine D4 receptor gene (DRD4) in smoking experimentation in adolescents and to
      determine the extent to which novelty seeking (NS) could account for a possible
      effect of DRD4 on tobacco use. METHOD: Participants were from a longitudinal
      study of an original birth cohort (born 1986-1988) of 384 children from a high
      risk community sample. At age 15 years, adolescents completed a self-report
      questionnaire measuring tobacco consumption and temperament (Junior Temperament
      and Character Inventory). DNA was taken from 303 participants (144 males, 159
      females) and genotyped for the DRD4 exon III polymorphism. RESULTS: DRD4 was
      associated with smoking status and NS in males but not in females. Males with the
      seven repeat allele exhibited more smoking involvement (p < .002) and scored
      higher in NS (p < .002) than males without this allele. In addition, elevated
      tobacco use was related to a higher level of NS in both males and females (p <
      .001). Multiple regression analyses revealed that NS mediated the relationship
      between DRD4 and smoking in males. CONCLUSIONS: These findings highlight the
      importance of considering the mechanisms underlying the association between
      genetic factors and tobacco use separately by gender and, possibly, by
      developmental period.

PMID- 15843771
TI  - The association between suicide screening practices and attempts requiring
      emergency care in juvenile justice facilities.
AB  - OBJECTIVE: To provide a national description of suicide screening practices in
      juvenile residential facilities and to examine their association with whether
      facilities experience a suicide attempt. METHOD: Multivariate modeling with data
      from the 2000 Juvenile Residential Facility Census (n = 3690 facilities).
      RESULTS: Controlling for facility characteristics, screening the entire facility
      population within the first 24 hours after arrival is significantly linked to
      lower odds of serious suicide attempts (odds ratio 0.23-0.65). Facilities
      screening just some of their population in a 2- to 7-day window after arrival
      exhibited significantly higher odds of serious suicide attempts (odds ratio 1.30
      4.73). CONCLUSIONS: Results suggest that facility-level risks of serious suicide
      attempts may be reduced by screening every child and adolescent entering a
      juvenile justice facility within the 24-hour window directly following arrival,
      regardless of the facility size and whether the youths came directly from another
      facility within the system.

PMID- 15843772
TI  - Clinicians' guide to evidence-based practice.

PMID- 15843773
TI  - Pharmacological management of treatment-induced insomnia in ADHD.

PMID- 15843782
TI  - Alendronate (Fosamax) and risedronate (Actonel) revisited.
AB  - A 10-year study of daily oral alendronate (Fosamax) and a 7-year study of daily
      oral risedronate (Actonel) indicate that both drugs maintained increases in bone
      mineral density (BMD) and decreases in markers of bone remodeling throughout the
      study period. Both drugs are now more commonly taken once weekly. Available data
      are insufficient to compare fracture rates with alendronate and risedronate, and
      fracture rates are considered the most important endpoint in osteoporosis
      studies. Recent reports of severe pain and jaw osteonecrosis with these drugs are
      disturbing.

PMID- 15843783
TI  - Ibandronate (Boniva): a new oral bisphosphonate.
AB  - In a 3-year study with 2.5 mg of ibandronate daily in postmenopausal women with
      at least 1 pre-existing vertebral fracture, the drug reduced new vertebral
      fractures by 50%, but had no effect on non-vertebral fractures. The 150-mg once
      monthly formulation of ibandronate was as effective as the daily one in
      increasing bone mineral density and decreasing bone turnover markers. It appears
      to be similar to alendronate and risedronate in efficacy and tolerability, but
      head-to-head comparisons are lacking.

PMID- 15843784
TI  - Palifermin (Kepivance) for myelotoxic-therapy-related mucositis.
AB  - Palifermin (Kepivance) is a recombinant keratinocyte growth factor that decreases
      the incidence and duration of severe oral mucositis (OM) in patients with
      hematologic malignancies receiving myelotoxic chemotherapy and hematopoietic stem
      cell support. It appears to be well tolerated and could decrease use of opioid
      analgesics and total parenteral nutrition in these patients.

PMID- 15843785
TI  - Homicide and suicide rates--national violent death reporting system, six states,
      2003.
AB  - In 2003, CDC instituted a new surveillance system, the National Violent Death
      Reporting System (NVDRS); the system collects detailed information regarding
      violent deaths from multiple sources. This report describes preliminary 2003 data
      from the first six states that participated in NVDRS and compares these data with
      1993-2002 data from the National Vital Statistics System (NVSS). The findings
      indicate a substantial increase in homicide rates among young males from 2002 to
      2003 and substantial increases in both homicide and suicide rates among males
      from 2000 to 2003. These findings underscore the need for states to have timely
      information for effective violence-prevention programs.

PMID- 15843786
TI  - Assessing the National Electronic Injury Surveillance System-Cooperative Adverse
      Drug Event Surveillance project--six sites, United States, January 1-June 15,
      2004.
AB  - Adverse drug events (ADEs) occur when therapeutic drugs have injurious effects;
      current systems for conducting national ADE surveillance are limited, and current
      national estimates of ADE incidence are problematic. In 2003, CDC, in
      collaboration with the Consumer Product Safety Commission (CPSC) and the Food and
      Drug Administration (FDA), created the National Electronic Injury Surveillance
      System-Cooperative Adverse Drug Event Surveillance (NEISS-CADES) project by
      adding active surveillance of ADEs to the National Electronic Injury Surveillance
      System-All Injury Program (NEISS-AIP). Because ADEs can be more difficult to
      identify than other injuries, an independent chart review in a sample of six
      NEISS-CADES hospitals was conducted to evaluate the sensitivity and predictive
      value positive (PVP) of ADE identification. This report describes the results of
      that evaluation, which indicated that although PVP for ADEs was high, the
      sensitivity was low, particularly for certain types of ADEs. As a result of these
      findings, additional training on identifying and reporting ADEs was initiated for
      all NEISS-CADES hospital coders. As more persons in the United States use drug
      therapies, active, postmarketing surveillance of ADEs can help identify safety
      problems and guide prevention efforts.

PMID- 15843787
TI  - Congenital malaria--Nassau County, New York, 2004.
AB  - Human malaria is a parasitic disease caused by four distinct species of
      intraerythrocytic protozoa of the genus Plasmodium. The parasites are transmitted
      to persons by the bite of an infective female Anopheles mosquito and rarely
      through blood transfusion and congenital transmission. The majority of malarial
      infections reported in the United States are acquired abroad by recent immigrants
      or persons returning from areas where malaria is endemic. This report describes
      the first documented case of congenital malaria acquired in Nassau County, New
      York, which is the fifth case of congenital malaria reported in the United States
      since 2000. Health-care providers should consider malaria as a diagnosis in
      neonates and young infants, particularly those with fever, whose mothers
      emigrated from areas where malaria is endemic.

PMID- 15843788
TI  - The astrocyte--neuron lactate shuttle: a debated but still valuable hypothesis
      for brain imaging.

PMID- 15843789
TI  - Altered functional connectivity related to white matter changes inside the
      working memory network at the very early stage of MS.
AB  - Functional magnetic resonance imaging (fMRI) using paced auditory serial addition
      test (PASAT) as paradigm was used to study the functional connectivity in 18
      patients at the very early stage of multiple sclerosis (MS) compared with 18
      controls, to determine the existence of circuitry disturbance inside the working
      memory network and its relationship with white matter abnormalities assessed by
      conventional MRI and magnetization transfer ratio (MTR) imaging. The left BA
      45/46 was selected as the seed region to compute correlation maps with other
      brain regions. After obtaining the correlation map for each subject, between
      group comparisons were performed using random effect procedure. Compared with
      controls, patients did not show any greater functional connectivity between left
      BA 45/46 and other regions during PASAT. In contrast, decrease in functional
      connectivity was observed in patients between left BA 45/46 and left BA 9, right
      BA 3, and the anterior cingulate cortex (BA 24). In patients, no correlations
      were found between altered functional connectivity and clinical data. However,
      functional connectivity observed between left BA 45/46 and BA 24 in patients was
      correlated with the MTR of normal appearing white matter, and with brain T(2)
      lesion load. Altered functional connectivity is present inside the working memory
      network of patients at the very early stage of MS and is related to the extent of
      diffuse white matter changes.

PMID- 15843790
TI  - SOD1 overexpression and female sex exhibit region-specific neuroprotection after
      global cerebral ischemia due to cardiac arrest.
AB  - Cardiac arrest is often associated with poor neurologic outcome since therapeutic
      options are limited. We tested the hypothesis that overexpression of CuZn
      superoxide dismutase (SOD+/-) is neuroprotective in a new murine model of cardiac
      arrest and cardiopulmonary resuscitation (CPR). Second, we investigated if female
      and male mice sustain similar injury and if sex-specific outcomes are altered by
      SOD overexpression. Neuronal injury was quantified 3 days after 8 mins of KCl
      induced cardiac arrest by calculating the percentage of ischemic neurons for
      caudoputamen and hippocampal CA1 region. In rostral caudoputamen, less neuronal
      cell loss was found for SOD+/- mice (31%+/-22%) when compared with wild-type (WT)
      mice (47%+/-31%, P<0.05). Superoxide dismutase overexpression did not reduce
      injury in the caudal caudoputamen. No sex-linked protection was evident in either
      genotype in the caudoputamen. Female WT mice had less CA1 injury than male WT
      mice (26%+/-31% versus 54%+/-30%, P<0.05), whereas no sex difference was found in
      SOD+/- mice (female: 42%+/-29%; male: 37%+/-37%). Comparison of hippocampal
      injury between genotypes revealed no differences for either males or females. In
      conclusion, SOD1 overexpression and female sex were associated with significant
      neuroprotection in this murine cardiac arrest model. However, no additive
      neuroprotection was observed, and these beneficial effects were restricted to
      specific brain regions.

PMID- 15843791
TI  - Functional recovery of neuronal activity in rat whisker-barrel cortex sensory
      pathway from freezing injury after transplantation of adult bone marrow stromal
      cells.
AB  - The effect of transplantation of adult bone marrow stromal cells (MSCs) into the
      freeze-lesioned left barrel field cortex in the rat was investigated by
      measurement of local cerebral glucose utilization (lCMR(glc)) in the anatomic
      structures of the whisker-to-barrel cortex sensory pathway. Bone marrow stromal
      cells or phosphate-buffered saline (PBS) were injected intracerebrally into the
      boundary zone 1 h after induction of the freezing cortical lesion. Three weeks
      after surgery, the 2-[(14)C]deoxyglucose method was used to measure lCMR(glc)
      during right whisker stimulation. The volume of the primary necrotic freezing
      lesion was significantly reduced (P<0.05), and secondary retrograde degeneration
      in the left ventral posteromedial (VPM) thalamic nucleus was diminished in the
      MSC-treated group. Local cerebral glucose utilization measurements showed that
      the freezing cortical lesion did not alter the metabolic responses to stimulation
      in the brain stem trigeminal nuclei, but eliminated the responses in the left VPM
      nucleus and periphery of the barrel cortex in the PBS-treated group. The
      left/right (stimulated/unstimulated) lCMR(glc) ratios were significantly improved
      in both the VPM nucleus and periphery of the barrel cortex in the MSC-treated
      group compared with the PBS-treated group (P<0.05). These results indicate that
      MSC transplantation in adults may stimulate metabolic and functional recovery in
      injured neuronal pathways.

PMID- 15843792
TI  - The 50-year war.

PMID- 15843793
TI  - Integrating HIV testing into immunological studies of non-HIV-related diseases.
AB  - HIV testing is now required for non-HIV-AIDS-related immunological studies in
      areas of high HIV prevalence. Ethical guidelines for testing in these
      circumstances need clarification and sensitive protocols need to be developed.

PMID- 15843794
TI  - Chemokines as immunotransmitters?

PMID- 15843795
TI  - Integrin activation under flow: a local affair.

PMID- 15843796
TI  - HIV pathogenesis: the first cut is the deepest.

PMID- 15843797
TI  - Resolving a case of split personality.

PMID- 15843798
TI  - MHC restriction: slip-sliding away.

PMID- 15843800
TI  - Interactions of NF-kappaB with chromatin: the art of being at the right place at
      the right time.
AB  - Transcription factors of the NF-kappaB family are essential regulators of the
      inflammatory and immune responses. The main 'switch' in NF-kappaB activation is
      cytoplasmic and leads to the release of NF-kappaB proteins from IkappaB
      molecules, specific inhibitors that prevent their nuclear accumulation. However,
      it is becoming increasingly apparent that in addition to this required activation
      step, both recruitment of NF-kappaB to target genes and NF-kappaB-induced
      transcriptional events after recruitment are actively controlled. Regulated
      recruitment of NF-kappaB to chromatin generates kinetic complexity in NF-kappaB
      dependent gene induction and 'wires' NF-kappaB-regulated gene activity to
      simultaneously activated pathways and transcription factors.

PMID- 15843801
TI  - A Pax3/Pax7-dependent population of skeletal muscle progenitor cells.
AB  - During vertebrate development, successive phases of embryonic and fetal
      myogenesis lead to the formation and growth of skeletal muscles. Although the
      origin and molecular regulation of the earliest embryonic muscle cells is well
      understood, less is known about later stages of myogenesis. We have identified a
      new cell population that expresses the transcription factors Pax3 and Pax7
      (paired box proteins 3 and 7) but no skeletal-muscle-specific markers. These
      cells are maintained as a proliferating population in embryonic and fetal muscles
      of the trunk and limbs throughout development. Using a stable green fluorescent
      protein (GFP) reporter targeted to Pax3, we demonstrate that they constitute
      resident muscle progenitor cells that subsequently become myogenic and form
      skeletal muscle. Late in fetal development, these cells adopt a satellite cell
      position characteristic of progenitor cells in postnatal muscle. In the absence
      of both Pax3 and Pax7, further muscle development is arrested and only the early
      embryonic muscle of the myotome forms. Cells failing to express Pax3 or Pax7 die
      or assume a non-myogenic fate. We conclude that this resident Pax3/Pax7-dependent
      progenitor cell population constitutes a source of myogenic cells of prime
      importance for skeletal muscle formation, a finding also of potential value in
      the context of cell therapy for muscle disease.

PMID- 15843802
TI  - A common somitic origin for embryonic muscle progenitors and satellite cells.
AB  - In the embryo and in the adult, skeletal muscle growth is dependent on the
      proliferation and the differentiation of muscle progenitors present within muscle
      masses. Despite the importance of these progenitors, their embryonic origin is
      unclear. Here we use electroporation of green fluorescent protein in chick
      somites, video confocal microscopy analysis of cell movements, and quail-chick
      grafting experiments to show that the dorsal compartment of the somite, the
      dermomyotome, is the origin of a population of muscle progenitors that contribute
      to the growth of trunk muscles during embryonic and fetal life. Furthermore, long
      term lineage analyses indicate that satellite cells, which are known progenitors
      of adult skeletal muscles, derive from the same dermomyotome cell population. We
      conclude that embryonic muscle progenitors and satellite cells share a common
      origin that can be traced back to the dermomyotome.

PMID- 15843803
TI  - Psychopharmacology of male rat sexual behavior: modeling human sexual
      dysfunctions?
AB  - Most of our current understanding of the neurobiology, neuroanatomy and
      psychopharmacology of sexual behavior and ejaculatory function has been derived
      from preclinical studies in the rat. When a large population of male rats is
      tested on sexual activity during a number of successive tests, over time
      individual rats display a very stable sexual behavior that is either slow, normal
      or fast as characterized by the number of ejaculations performed. These sexual
      endophenotypes are postulated as rat counterparts of premature (fast rats) or
      retarded ejaculation (slow rats). Psychopharmacology in these endophenotypes
      helps to delineate the underlying mechanisms and pathology. This is illustrated
      by the effects of serotonergic antidepressants and serotonergic compounds on
      sexual and ejaculatory behavior of rats. These preclinical studies and models
      contribute to a better understanding of the neurobiology of ejaculation and boost
      the development of novel drug targets to treat ejaculatory disorders such as
      premature and retarded ejaculation.

PMID- 15843804
TI  - Ultrastructural comparison of penile cavernous tissue between hypertensive and
      normotensive rats.
AB  - Our aim was to compare the ultrastructure of penile cavernous tissue in the
      spontaneous hypertensive rat (SHR) and normotensive rat, and study the relation
      of blood pressure with erectile function. After injection of apomorphine (APO),
      penile erectile frequency in 16-week-old SHR (group A) and Wistar-Kyoto rat (WKY)
      (group B) was observed and noted. The ultrastructure of the penile cavernous
      tissue was studied by scanning electron microscope and transmission electron
      microscope. The mean blood pressures were significantly higher in group A than in
      group B (P=0; 171.20+/-10.94 and 117.60+/-12.38, n=5, for group A and group B,
      respectively). After treatment of the two groups with APO, the erectile frequency
      in group A was significantly less than in group B (P=0.007; 0.40+/-0.55 and
      2.40+/-1.14, n=5, for group A and group B, respectively). Significant
      ultrastructural pathological changes were observed in the tunica albuginea and
      penile cavernous tissue of SHR. The elastic fibers were decreased and the
      collagen fibers of the sinusoid were increased in group A. The tunica albuginea
      thickness (mean+/-s.d.) was 100.20+/-7.22 microm and 126.00+/-7.65 microm in
      group A and group B, respectively. The tunica albuginea of group A was
      significantly thinner than that in B (P=0.001). Some endothelial cells and smooth
      muscle cells exhibited damaged mitochondria, and endoplasmic reticulums and
      Schwann cells were degenerated in group A. Although the function of penile
      erection might be affected by a secondary effect related to endothelial
      dysfunction of hypertension, these ultrastructural pathological changes of the
      penile cavernous tissue might also be one of the important mechanisms of erectile
      dysfunction caused by hypertension.

PMID- 15843805
TI  - Are questions on both achieving and maintaining an erection needed to define
      erectile dysfunction?
AB  - Our aim was to ascertain if the assessment of erectile dysfunction (ED) should
      include questions on difficulty in both achieving and maintaining erection. A
      population-based study of 3143 men in Tampere region in Finland was conducted by
      mailed questionnaire. The 1983 men who responded questions on erectile function
      were included in the analysis. Different levels in the severity of ED were used
      to examine the agreement between the two questions. Consistency was measured by
      kappa coefficient. Consistency was fairly high (kappa=0.71) when the severity of
      ED was examined in four groups. In those cases where alternative responses were
      categorized into three groups, consistency was best (kappa=0.86) when the
      alternatives 'never' and 'sometimes' were combined. Consistency was almost
      perfect (kappa=0.97) when ED dichotomized into two groups and the cutoff was set
      between the alternatives 'quite often' and 'intercourse does succeed'. The kappa
      index was 0.86 with the cutoff level between 'sometimes' and 'quite often' and
      0.67 with the cutoff between 'never' and 'sometimes'. When ED was examined in
      different age groups, the consistency was the highest among the oldest
      respondents. Responses on both symptoms are needed to distinguish between normal
      erectile function and minimal ED, and also between minimal and moderate ED,
      especially in young men. When the aim is to distinguish between complete ED and a
      milder form, the information from one question is the same as that from two
      questions.

PMID- 15843806
TI  - A novel adenoviral vector which mediates hypoxia-inducible gene expression
      selectively in neurons.
AB  - Selective gene expression in neurons is still a challenge. We have developed
      several expression vectors using a combination of neuron restrictive silencer
      elements (NRSEs), hypoxia responsive elements (HREs) and CMV minimal promoter
      (CMVmp). These elements were packaged into replication defective adenovirus to
      target gene expression selectively in neurons in a hypoxia-regulated manner.
      Neuronal selectivity and responsiveness to hypoxia of these novel constructs were
      determined empirically in both neural cell lines and primary cerebellar granule
      neurons (CGNs). The construct p5HRE-3NRSE exhibited not only the highest level of
      reporter gene expression in neuronal cells but also in an oxygen concentration
      dependent manner when compared with all other constructs. As expected, this
      construct did not elicit reporter gene expression in non-neuronal cells including
      human HEK293A and HT29 cells, rat NRK cells, mouse 3T6 cells and 3T3 L1 cells.
      This construct was packaged into a replication defective adenoviral vector
      (Ad/5HRE-3NRSE) to determine neuron-selective and hypoxia-inducible gene
      expression in cultured mouse postmitotic primary CGNs and differentiated human
      NT2 neurons (NT2/Ns). Remarkably, in response to hypoxia, Ad/5HRE-3NRSE showed
      strong hypoxia-inducible gene expression selectively in neurons (12-fold
      induction in CGNs and 22-fold in NT2/Ns), but not in glial cells. Taken together,
      this vector with restricted gene expression to neurons under the regulation of
      hypoxia will be a useful tool for investigations of mechanisms of neuronal damage
      caused by ischemic insult.

PMID- 15843807
TI  - Induction of human papilloma virus E6/E7-specific cytotoxic T-lymphocyte activity
      in immune-tolerant, E6/E7-transgenic mice.
AB  - Despite promising preclinical results of various therapeutic anticancer
      immunization strategies, these approaches may not be effective enough to
      eradicate tumors in cancer patients. While most animal models are based on fast
      growing transplantable tumors, malignancies in, for example, cervical cancer
      patients in general develop much more slowly, which may lead to immune
      suppression and/or immune tolerance. As a consequence, the immunomodulating
      signal of any therapeutic immunization regimen should be sufficiently potent to
      overcome this immunocompromised condition. In previous studies, we demonstrated
      that an experimental vaccine against human papillomavirus (HPV)-induced cervical
      cancer, based on Semliki Forest virus (SFV), induces robust HPV-specific cellular
      immune responses in mice. Now we studied whether this strategy is potent enough
      to also prime a cellular immune response in immune-tolerant HPV transgenic mice,
      in which CTL activity cannot be induced using protein or DNA vaccines. We
      demonstrate that, depending on the route of immunization, SFV-expressing HPV16 E6
      and E7 indeed has the capacity to induce HPV16 E7-specific cytotoxic T cells in
      HPV-transgenic mice.

PMID- 15843808
TI  - Targeting non-human coronaviruses to human cancer cells using a bispecific single
      chain antibody.
AB  - To explore the potential of using non-human coronaviruses for cancer therapy, we
      first established their ability to kill human tumor cells. We found that the
      feline infectious peritonitis virus (FIPV) and a felinized murine hepatitis virus
      (fMHV), both normally incapable of infecting human cells, could rapidly and
      effectively kill human cancer cells artificially expressing the feline
      coronavirus receptor aminopeptidase N. Also 3-D multilayer tumor spheroids
      established from such cells were effectively eradicated. Next, we investigated
      whether FIPV and fMHV could be targeted to human cancer cells by constructing a
      bispecific single-chain antibody directed on the one hand against the feline
      coronavirus spike protein--responsible for receptor binding and subsequent cell
      entry through virus-cell membrane fusion--and on the other hand against the human
      epidermal growth factor receptor (EGFR). The targeting antibody mediated specific
      infection of EGFR-expressing human cancer cells by both coronaviruses.
      Furthermore, in the presence of the targeting antibody, infected cancer cells
      formed syncytia typical of productive coronavirus infection. By their potent
      cytotoxicity, the selective targeting of non-human coronaviruses to human cancer
      cells provides a rationale for further investigations into the use of these
      viruses as anticancer agents.

PMID- 15843810
TI  - Regeneration of dystrophin-expressing myocytes in the mdx heart by skeletal
      muscle stem cells.
AB  - Cell transplantation holds promise as a potential treatment for cardiac
      dysfunction. Our group has isolated populations of murine skeletal muscle-derived
      stem cells (MDSCs) that exhibit stem cell-like properties. Here, we investigated
      the fate of MDSCs after transplantation into the hearts of dystrophin-deficient
      mdx mice, which model Duchenne muscular dystrophy (DMD). Transplanted MDSCs
      generated large grafts consisting primarily of numerous dystrophin-positive
      myocytes and, to a lesser degree, dystrophin-negative non-myocytes that expressed
      an endothelial phenotype. Most of the dystrophin-positive myocytes expressed a
      skeletal muscle phenotype and did not express a cardiac phenotype. However, some
      donor myocytes, located at the graft-host myocardium border, were observed to
      express cardiac-specific markers. More than half of these donor cells that
      exhibited a cardiac phenotype still maintained a skeletal muscle phenotype,
      demonstrating a hybrid state. Sex-mismatched donors and hosts revealed that many
      donor-derived cells that acquired a cardiac phenotype did so through fusion with
      host cardiomyocytes. Connexin43 gap junctions were not expressed by donor-derived
      myocytes in the graft. Scar tissue formation in the border region may inhibit the
      fusion and gap junction connections between donor and host cells. This study
      demonstrates that MDSC transplantation warrants further investigation as a
      potential therapy for cardiac dysfunction in DMD.

PMID- 15843809
TI  - HSV-mediated gene transfer of vascular endothelial growth factor to dorsal root
      ganglia prevents diabetic neuropathy.
AB  - We examined the utility of herpes simplex virus (HSV) vector-mediated gene
      transfer of vascular endothelial growth factor (VEGF) in a mouse model of
      diabetic neuropathy. A replication-incompetent HSV vector with VEGF under the
      control of the HSV ICP0 promoter (vector T0VEGF) was constructed. T0VEGF
      expressed and released VEGF from primary dorsal root ganglion (DRG) neurons in
      vitro, and following subcutaneous inoculation in the foot, expressed VEGF in DRG
      and nerve in vivo. At 2 weeks after induction of diabetes, subcutaneous
      inoculation of T0VEGF prevented the reduction in sensory nerve amplitude
      characteristic of diabetic neuropathy measured 4 weeks later, preserved autonomic
      function measured by pilocarpine-induced sweating, and prevented the loss of
      nerve fibers in the skin and reduction of neuropeptide calcitonin gene-related
      peptide and substance P in DRG neurons of the diabetic mice. HSV-mediated
      transfer of VEGF to DRG may prove useful in treatment of diabetic neuropathy.

PMID- 15843811
TI  - Fetal laryngeal stenosis/atresia and congenital high airway obstructive syndrome
      (CHAOS): a case report.
AB  - Congenital high airway obstructive syndrome (CHAOS) is a rare but fatal disease
      with predictably characteristic features including stenotic or atretic upper
      airway, hyperplastic lungs, elevated diaphragm, massive fetal ascites and fetal
      hydrops. Diagnosis of CHAOS by ultrasound scan is possible and clinically
      important since advanced intrauterine surgery to correct the defect is possible.
      We report a case of fetus of CHAOS with massive ascites, pulmonary hyperplasia
      and laryngeal stenosis/atresia. We feel that it is important to recognize the
      entity both by ultrasound scan and by the pathologist so that some cases can be
      corrected by intrauterine fetal surgery.

PMID- 15843812
TI  - Effects of pressure support during an acute reduction of synchronized
      intermittent mandatory ventilation in preterm infants.
AB  - BACKGROUND: During weaning of synchronized intermittent mandatory rate in preterm
      infants, the spontaneous breaths must overcome the resistance of the endotracheal
      tube and the disease-induced respiratory loads. Pressure Support (PS) can be used
      as an adjunct to synchronized intermittent mandatory ventilation (SIMV) to
      partially unload the spontaneous breaths. OBJECTIVE: To evaluate the effects of
      two levels of PS as an adjunct to SIMV on gas exchange and breathing effort
      during an acute reduction in SIMV rate in preterm infants. METHODS: In all, 15
      infants (birth weight 793 +/- 217 g, gestational age 26.4 +/- 1.5 weeks,
      postnatal age 15 +/- 16 days). Ventilatory support consisted of SIMV with peak
      inspiratory pressure (PTP) 16.3 +/- 1.3 cmH(2)O, positive end-expiratory pressure
      (PEEP) 4.3 +/- 0.6 cmH(2)O, and fraction of inspired oxygen (FiO(2)) 0.26 +/-
      0.06. Infants were studied during four 30-minute periods: Two baseline SIMV
      periods and two periods of SIMV plus PS, in random order. During SIMV + PS, SIMV
      rate was lowered by 10 breaths per minute (b/minute) and PS was set at 3 and 6
      cmH(2)O (SIMV+PS3 and SIMV + PS6, respectively). RESULTS: SIMV rate was reduced
      during SIMV + PS from 21.4 +/- 6.6 to 11.4 +/- 6.6 b/minute. Arterial oxygen
      saturation, transcutaneous carbon dioxide tension and FiO(2) remained unchanged.
      Minute ventilation, total respiratory rate and mean airway pressure were higher
      during SIMV + PS. Per-breath inspiratory effort was lower during SIMV + PS and
      this was more striking during SIMV + PS6. Spontaneous inspiratory effort per
      minute increased during SIMV + PS3, but this increase was averted during SIMV +
      PS6. CONCLUSION: Assistance of the spontaneous breaths with pressure support
      maintained gas exchange. PS of 6 cm H(2)O prevented an increase in breathing
      effort during an acute 50% reduction in SIMV rate.

PMID- 15843813
TI  - Terminal deletion of chromosome 15q26.1: case report and brief literature review.
AB  - Terminal deletions of chromosome 15q are rare events, with only six cases
      previously described. Here we describe a seventh case of a terminal deletion of
      the long arm of chromosome 15, with the present case exhibiting clinical features
      not previously described.

PMID- 15843814
TI  - The association between early tracheal colonization and bronchopulmonary
      dysplasia.
AB  - OBJECTIVE: To evaluate the relationship between early tracheal colonization and
      bronchopulmonary dysplasia (BPD). STUDY DESIGN: This is a retrospective cohort
      study which included 308 inborn neonates admitted to the newborn intensive care
      unit at the University of Miami Jackson Memorial Medical Center between January
      1997 and December 2000 with birthweight 500 to 1000 g, who required mechanical
      ventilation on the first day of life. Chorioamnionitis was diagnosed by maternal
      symptoms and histopathopathology. Tracheal cultures were obtained immediately
      after tracheal intubation. BPD was diagnosed in neonates who had supplemental
      oxygen requirement for more than 28 days. Pearson's chi(2) and Logistic
      Regression Analysis were used to evaluate the relationship between
      chorioamnionitis, positive initial tracheal cultures and BPD, after adjusting for
      confounding variables. RESULTS: In patients with chorioamnionitis, the incidence
      of early positive tracheal cultures was 41% compared to 16% in those without
      chorioamnionitis, (p < 0.00001). In patients with birthweight 700 to 1000 g, a
      positive early tracheal culture increased the risk of BPD (OR = 2.42, CI 1.05 to
      5.62, p < 0.05). CONCLUSION: Preterm infants exposed to chorioamnionitis have an
      increased incidence of early tracheal colonization. This early tracheal
      colonization may predispose them to develop BPD.

PMID- 15843815
TI  - Transient bilirubin encephalopathy and apnea of prematurity in 28 to 32 weeks
      gestational age infants.
AB  - OBJECTIVE: Apnea of prematurity (AoP) is, in part, a reflection of brainstem
      mediated respiratory control system maturation. We previously demonstrated
      changes in brainstem function in relation to hyperbilirubinemia (bilirubin
      encephalopathy, (BE)) as evaluated by auditory brainstem evoked responses (ABR)
      in infants 28 to 32 weeks gestational age (GA). We hypothesized that in this
      population, as bilirubin increases and causes auditory brainstem dysfunction,
      respiratory control system may also be adversely affected leading to increased
      frequency of AoP. STUDY DESIGN: We studied 100, 28 to 32 weeks GA infants and
      identified 66 with normal and 34 with abnormal ABR progression in temporal
      relation to hyperbilirubinemia (BE). The abnormal ABR progression was associated
      with elevated bilirubin, specifically elevated unbound bilirubin levels. A
      blinded, retrospective chart review quantified the amount of weekly apnea and
      bradycardia events during the hospital stay, total duration of methylxanthine
      treatment, total duration of mechanical ventilation, CPAP, and/or nasal cannula,
      and risk factors for apnea (sepsis, IVH grade >II, asphyxia). Since mechanical
      ventilation confounds the identification of apnea, infants requiring mechanical
      ventilation were excluded from further review (n = 60; 21 with BE and 39 with
      normal ABR progression). Data from the remaining 40 infants were analyzed.
      Student's t-test was used to analyze continuous variables if the distribution was
      normal otherwise Wilcoxon-ranked-sum test was used. chi(2) was used to analyze
      nominal variables. A p < or =0.05 was considered significant. RESULTS: There was
      no difference in risk factors between infants with and without BE. BE was
      identified on day 3 (median; range 1 to 6 days). Patients with BE had
      significantly more apneic events (15 vs 2, p = 0.0009), bradycardic events (14 vs
      1, p = 0.02), and required more prolonged treatment with CPAP (2.2 vs 0.5 days, p
      = 0.007), nasal cannula (6.6 vs 2.2 days, p = 0.02), and methylxanthines (9.5 vs.
      1.9 days, p = 0.002) than those with normal ABR progression. The difference in
      the incidence of apnea and bradycardia between infants with and without BE was
      most pronounced during the first week. CONCLUSIONS: Premature infants with
      transient bilirubin encephalopathy as defined by abnormal ABR progression in
      relation to hyperbilirubinemia have more concurrent apneic events and require
      more prolonged respiratory support and medications.

PMID- 15843816
TI  - Maintained rules of development in a mouse B-cell tumor.

PMID- 15843817
TI  - The role of reduced intensity conditioning allogeneic stem cell transplantation
      in patients with acute myeloid leukemia: a donor vs no donor comparison.
AB  - Using a genetic randomization through a 'donor' vs 'no donor' comparison, the aim
      of this analysis was to assess the real benefit of reduced intensity conditioning
      allogeneic stem cell transplantation (RIC-allo-SCT) among 95 adult high-risk
      acute myeloid leukemia (AML) patients. In an 'intention-to-treat' analysis,
      leukemia-free survival (LFS) was significantly higher in the 'donor' group as
      compared to the 'no donor' group (P=0.01; 54 vs 30% at 4 years). The latter held
      true when restricting the analysis to the 25 patients who could actually receive
      the RIC-allo-SCT (P=0.001). Overall transplant-related mortality in the
      'transplant' group was 12%, with overall survival (OS) being significantly higher
      in the 'transplant' group as compared to the 'no transplant' group (P=0.01).
      Also, in the 'intention-to-treat' analysis, OS was significantly higher in the
      'donor' group as compared to the 'no donor' group (P=0.04). In the multivariate
      analysis, actual performance of RIC-allo-SCT (P=0.001; RR=4.0; 95% CI, 1.7-9.6)
      was the strongest factor significantly predictive of an improved LFS. We conclude
      that if a matched related donor is identified, RIC-allo-SCT should be proposed
      for AML patients not eligible for standard myeloablative allo-SCT.

PMID- 15843818
TI  - CDKN2 deletions have no prognostic value in childhood precursor-B acute
      lymphoblastic leukaemia.

PMID- 15843819
TI  - MLL methylation is not likely a common mechanism for therapy-related AML.

PMID- 15843820
TI  - Therapeutic research in untreated acute promyelocytic leukemia.

PMID- 15843821
TI  - High-dose cytarabine and mitoxantrone in consolidation therapy for acute
      promyelocytic leukemia.
AB  - The objective of our study was to evaluate high-dose cytarabine in consolidation
      therapy in patients with newly diagnosed acute promyelocytic leukemia (APL).
      Patients (age 16-60 years) received induction therapy according to the AIDA
      protocol (all-trans retinoic acid, idarubicin) followed by one cycle of ICE
      (idarubicin, cytarabine, etoposide) and two cycles of HAM (cytarabine 3 g/m(2)
      q12h, days 1-3; mitoxantrone 10 mg/m(2), days 2 and 3). From 1995 to 2003, 82
      patients were enrolled. In total, 72 patients (88%) achieved a complete
      remission, and 10 patients (12%) died from early/hypoplastic death (ED/HD). A
      total of 71 patients received at least one cycle of HAM. Relapse-free survival
      (RFS) and overall survival (OS) after 46 months were 83 and 82%, respectively.
      White blood cell count above 10.0 x 10(9)/l at diagnosis and additional
      chromosomal aberrations were unfavorable prognostic markers for OS, whereas no
      prognostic markers for RFS were identified including FLT3 mutations. In
      conclusion, high-dose cytarabine in consolidation therapy for patients with newly
      diagnosed APL is an effective treatment approach.

PMID- 15843822
TI  - Expression profile of survivin in acute leukaemias: the importance of
      differential splicing.

PMID- 15843823
TI  - T-cell ZAP-70 overexpression in chronic lymphocytic leukemia (CLL) correlates
      with CLL cell ZAP-70 levels, clinical stage and disease progression.

PMID- 15843824
TI  - Identification of e19a2 BCR-ABL fusions (mu-BCR breakpoints) at the DNA level by
      ligation-mediated PCR.

PMID- 15843825
TI  - Dichotomy of all-trans retinoic acid inducing signals for adult T-cell leukemia.
AB  - We previously reported that all-trans retinoic acid (ATRA) inhibits growth in
      human T-cell leukemia virus type 1 (HTLV-1)-positive T-cell lines and fresh cells
      from patients with adult T-cell leukemia. However, the mechanism of this
      inhibition is not clear. In the present study, we observed that NF-kappaB
      transcriptional activity as well as cell growth decreased significantly in HTLV-1
      positive T-cell lines in the presence of ATRA. Furthermore, we observed that ATRA
      reduced HTLV-1 proviral DNA, HTLV-1 genes (gag, tax, or pol mRNA) using the real
      time quantitative polymerase chain reaction. SIL-2R was reduced by ATRA in both
      protein level (culture supernantant) and mRNA level in HTLV-1-positive T-cell
      lines. Interestingly, ATRA significantly inhibited RT activity similar to
      azidothimidine (AZT) in HTLV-1-positive T-cell lines. Moreover, AZT inhibited
      proviral DNA but not NF-kappaB transcriptional activity, and sIL-2R on HTLV-1;
      however, ATRA inhibited of NF-kappaB, proviral DNA and sIL-2R on HTLV-1. These
      results suggested that the decrease in sIL-2R induced by ATRA may be caused by
      the actions of a NF-kappaB inhibitor acting on the NF-kappaB/sIL-2R signal
      pathway. These results suggested that ATRA could have two roles, as a NF-kappaB
      inhibitor and as an RT inhibitor.

PMID- 15843826
TI  - Antimyeloma effects of a novel synthetic retinoid Am80 (Tamibarotene) through
      inhibition of angiogenesis.
AB  - In multiple myeloma (MM), the interaction between myeloma cells and bone marrow
      microenvironment has an important role in the pathogenesis of MM. We first
      examined the inducing effect of myeloma cells on migration of human umbilical
      vein vascular endothelial cells (HUVECs). Five myeloma cell lines produced
      varying amounts of VEGF, and migration of HUVECs was induced by coculture with
      myeloma cells. We next examined the inhibitory effect of a novel synthetic
      retinoid Am80 (Tamibarotene) on both myeloma cells and HUVECs. Am80 is specific
      for the retinoic-acid receptor-alpha/beta, and has therapeutic effects in all
      trans retinoic acid resistant acute promyelocytic leukemia. Am80 slightly
      inhibited the growth of both myeloma cells and HUVECs, and remarkably inhibited
      the growth of HUVECs stimulated by VEGF. Am80 showed little growth inhibition of
      bone marrow stromal cells (BMSCs), but it markedly inhibited migration of HUVECs
      by cocultured myeloma cells. Am80 inhibited VEGF-induced phosphorylation of VEGF
      receptor. In addition, VEGF-induced formation of tube-like structures in vitro
      and neovascularization in mouse corneas were significantly inhibited by Am80.
      These findings clearly demonstrate that Am80 is a potential inhibitor of
      angiogenesis caused by the interaction between vascular endothelial cells and
      myeloma cells, and might be a useful therapeutic agent against MM.

PMID- 15843827
TI  - Gene expression profiling of leukemic cell lines reveals conserved molecular
      signatures among subtypes with specific genetic aberrations.
AB  - Hematologic malignancies are characterized by fusion genes of biological/clinical
      importance. Immortalized cell lines with such aberrations are today widely used
      to model different aspects of leukemogenesis. Using cDNA microarrays, we
      determined the gene expression profiles of 40 cell lines as well as of primary
      leukemias harboring 11q23/MLL rearrangements, t(1;19)[TCF3/PBX1],
      t(12;21)[ETV6/RUNX1], t(8;21)[RUNX1/CBFA2T1], t(8;14)[IGH@/MYC],
      t(8;14)[TRA@/MYC], t(9;22)[BCR/ABL1], t(10;11)[PICALM/MLLT10],
      t(15;17)[PML/RARA], or inv(16)[CBFB/MYH11]. Unsupervised classification revealed
      that hematopoietic cell lines of diverse origin, but with the same primary
      genetic changes, segregated together, suggesting that pathogenetically important
      regulatory networks remain conserved despite numerous passages. Moreover, primary
      leukemias cosegregated with cell lines carrying identical genetic rearrangements,
      further supporting that critical regulatory pathways remain intact in
      hematopoietic cell lines. Transcriptional signatures correlating with clinical
      subtypes/primary genetic changes were identified and annotated based on their
      biological/molecular properties and chromosomal localization. Furthermore, the
      expression profile of tyrosine kinase-encoding genes was investigated,
      identifying several differentially expressed members, segregating with primary
      genetic changes, which may be targeted with tyrosine kinase inhibitors. The
      identified conserved signatures are likely to reflect regulatory networks of
      importance for the transforming abilities of the primary genetic changes and
      offer important pathogenetic insights as well as a number of targets for future
      rational drug design.

PMID- 15843828
TI  - Genetic heterogeneity of the hypervariable region I of Hepatitis C virus and
      lymphoproliferative disorders.
AB  - B-cell lymphoproliferative disorders (BCLD) have been associated with chronic
      hepatitis C virus (HCV) infection. The HCV glycoprotein E2 (gpE2) hypervariable
      region I (HVR-I) may be a potential antigenic candidate to promote B-cell
      proliferation. The purpose of this study was to analyze the influence of HVR-I
      sequence variability in the development of BCLD. HVR-I sequences were studied in
      29 chronically HCV-infected patients with (n=15) or without (n=14) BCLD. After
      PCR amplification of the gpE2 region, analysis of the 81 bp HVR-I encoding
      fragment was performed on 7-18 clones per patient. HVR-I sequence complexity was
      slightly lower in patients with BCLD (mean 0.347) than without (0.468) (P=0.2),
      though, sequence diversities were similar (0.0370 vs 0.0954, P=0.239).
      Phylogenetic analysis did not reveal any BCLD-associated clustering. In our
      population, neither the recently described insertion between positions 1 and 2 of
      HVR-I nor residues at positions 4 and 13 were particularly linked to BCLD. As
      previously described, we confirm the high degree of conservation of HVR-I
      residues T-2, G-6 and G-23 in our patients. Contrary to recent findings, our
      analysis based on multiple clones per patient analysis did not reveal any
      particular motif associated with BCLD.

PMID- 15843829
TI  - Regulation of cigarette smoke toxicity.

PMID- 15843830
TI  - Scope for regulation of cigarette smoke toxicity according to brand differences
      in published toxicant emissions.
AB  - AIMS: To explore the scope for regulating to reduce the toxicity of manufactured
      cigarettes sold in New Zealand (NZ), based on published toxicant emissions by
      brand. METHODS: Internet searches of published cigarette smoke emissions of 13
      toxicants chosen on risk assessment principles, for 20 British Columbian, 15
      Australian brands, and one NZ brand, Holiday Extra-mild (HEM), tested by Health
      Canada intensive smoke machine method at Labstat Inc, Kitchener, Ontario, as a
      ratio of toxicant to nicotine yield. We estimated relative overall smoke toxicity
      per disease group and per brand, after adjusting for the published cigarette
      attributed mortality fractions for cancer, cardiovascular, and respiratory
      disease. RESULTS: After allowing for nicotine yield, filter ventilation, and
      compensatory over-smoking, there were significant differences between brands,
      with the NZ brand estimated to be the most toxic. Low-yield cigarettes (<0.9 mg
      nicotine ISO) were estimated to be on average 19% more potent overall than medium
      yield cigarettes (p<0.01). Of toxicants identified and measurable in smoke; 1,3
      butadiene accounted for 45% of cancer potency; hydrogen cyanide for 89% of
      cardiovascular; and acrolein for 97% of respiratory potency--these three
      toxicants accounting for 65% of identified brand potency. Individual toxicant
      emissions varied across brands by a factor of 1.5 for carbon monoxide, to 32 for
      lead. Compared with HEM, one Canadian brand, 'Export A full flavor', carried a
      37% lower cancer risk. This lower risk was largely due to differences in nicotine
      yield, lowering the toxicant/nicotine ratio. CONCLUSIONS: Cigarettes,
      unregulated, are unduly dangerous. Though many smoke toxicants cannot yet be
      quantified, risk assessment based on current data suggests that regulation could
      partly reduce identifiable cancer risk, and possibly eliminate the excess
      cardiovascular and respiratory toxicity of HEM, when compared with regular
      Canadian brands. The first goal should be to reduce emissions of the leading
      three toxicants, in addition to more effective charcoal filters. Tobacco smoke,
      unlike unburnt or non-smoking tobacco, contains toxic gases and trillions of
      reactive oxygen species molecules per puff, and will remain inherently harmful.
      Regulation could usefully part-reduce smoke toxicity exposure for continuing
      smokers, while not relenting on efforts to assist smokers and society to be quit
      of smoking.

PMID- 15843831
TI  - Scope for regulation of cigarette smoke toxicity: the case for including charcoal
      filters.
AB  - AIM: To compare the emissions toxicity of two manufactured cigarette brands, one
      with and one without a charcoal filter, in the light of manufacturers' laboratory
      research findings on the properties of charcoal filters. METHOD: Emissions of
      Mild Seven charcoal filter brands, regular (labelled '12 mg tar') and Light
      (labelled '9 mg tar') purchased in 2004, were compared with those of Holiday
      Extra-mild brand (9 mg tar, acetate filter), purchased in 2002. All emissions
      were tested under intensive machine smoking conditions by Labstat International
      Inc., Kitchener, Ontario. RESULTS: The Mild Seven brands contained a small amount
      of charcoal, its black granules visible against the white acetate filter. The
      charcoal filter in the brands tested did not reduce toxicity to the extent
      expected, though they gave significantly lower emissions for the respiratory
      toxicants acrolein (14%-17% lower, p 'less than and equal to' 0.01) and
      formaldehyde (26-37% lower, p 'less than and equal to' 0.01). Reductions were not
      significant for acetaldehyde, and actually higher for hydrogen cyanide. Overall,
      estimated cardiovascular-respiratory toxicity was not reduced, whether based on
      toxicant emissions or the toxicant to nicotine ratios. Of the packet labels,
      neither tar yield (mg) nor the descriptors 'mild', 'light', or 'extra-mild', or
      'charcoal filter' for these three brands was associated with any reduction of the
      combined respiratory--and cardiovascular toxicity of mainstream smoke, as
      measured by leading toxicants tested by the intensive method. Previously secret
      documents from cigarette companies, including British American Tobacco, reported
      reductions of 75%-80% in hydrogen cyanide, acetaldehyde, acrolein, and
      formaldehyde in mainstream smoke from addition of charcoal to the filter. We
      estimated that an effective charcoal filter could reduce a brand's overall
      relative toxicity score for identifiable toxicant by over 40%. CONCLUSION: Since
      1965, major cigarette firms have known from their chemists that many smoke
      toxicants, including hydrogen cyanide and acrolein, were removable by
      manufacturing the cigarette with a charcoal filter. To this day, few brands have
      charcoal filters. The best known, Mild Seven, contained a token charcoal filter
      only. In neither Japan nor New Zealand did this brand lower cardiovascular
      toxicant emissions in smoke. In the Smoke-free Environments Act, Government has
      the power to lower smoke emissions by regulation, but no regulations are in
      place. The Act does not give power to add filters to cigarettes, but does give
      power to lower smoke emissions to the level attainable by using a charcoal
      filter, which could reduce smoke emission toxicity to a large extent. Regulation
      to require effective charcoal filters is now long overdue.

PMID- 15843832
TI  - Tobacco tax as a health protecting policy: a brief review of the New Zealand
      evidence.
AB  - AIM: To review the evidence relating to tobacco taxation as a health and equity
      protecting policy for New Zealand. METHODS: Searches of Medline, EconLit,
      ECONbase, Index NZ, and library databases for literature on tobacco taxation.
      RESULTS: The New Zealand evidence indicates that increases in tobacco prices are
      associated with decreases in tobacco consumption in the general population over
      the long term. This finding comes from multiple studies relating to: tobacco
      supplies released from bond, supermarket tobacco sales, household tobacco
      expenditure data, trends in smoking prevalence data, and from data on calls to
      the Quitline service. For the 1988-1998 period, the overall price elasticity of
      demand for all smoking households was estimated to be such that a 10% price
      increase would lower demand by 5% to 8%. Two studies are suggestive that
      increased tobacco affordability is also a risk factor for higher youth smoking
      rates. There is evidence from two studies that tobacco price increases reduce
      tobacco consumption in some low-income groups and one other study indicates that
      tobacco taxation is likely to be providing overall health benefit to low-income
      New Zealanders. These findings are broadly consistent with the very large body of
      scientific evidence from other developed countries. CONCLUSIONS: There is good
      evidence that tobacco taxation is associated with reduced tobacco consumption in
      the New Zealand setting, and some limited evidence for equity benefits from
      taxation increases. Substantial scope exists for improving tobacco taxation
      policy in New Zealand to better protect public health and to improve equity.

PMID- 15843833
TI  - Smoky homes: a review of the exposure and effects of secondhand smoke in New
      Zealand homes.
AB  - AIMS: To review the evidence of exposure to secondhand smoke (SHS) in New Zealand
      homes and its effects on health. METHODS: A search for relevant literature was
      made in April-May 2004, using Medline and other databases, and via inquiries to
      official and other agencies. Data on the types of households with smoking members
      were obtained by an analysis of 1996 Census data. RESULTS: National survey data
      indicate that at least 18% of all New Zealanders and 30% of Maori are exposed to
      SHS in the home. Surveys of high school students indicate home SHS exposure
      levels of 30% or more. The exposure appears to have decreased during 1996-2003
      for Maori and the general population (p<0.001 for trend for both), with low
      income households more likely to be exposed than others. There is an absence of
      exposure data for many specific population groups including pregnant women and
      infants. New Zealand evidence from two large cohort studies indicates an
      increased risk of death of at least 15% for never smokers, aged 45-74, if they
      live in a household with smokers. Over 250 deaths per year are estimated to be
      attributable to SHS exposure in New Zealand homes; over double the mortality from
      SHS exposure at work. CONCLUSIONS: Improved information on SHS exposure in the
      New Zealand setting is needed. The levels of home SHS exposure and estimated
      mortality burden justify a substantial Government and health-agency investment to
      reduce this exposure, particularly for children, Maori, and those in low-income
      households.

PMID- 15843834
TI  - Rethinking the regulatory framework for tobacco control in New Zealand.
AB  - Tobacco is a particularly unusual consumer product in that it is highly
      addictive, kills over half its long-term users, and is a major cause of premature
      death and health inequalities in New Zealand. We therefore examined the place of
      regulatory frameworks in advancing tobacco control, and suggest the formation of
      a Government Tobacco Authority. Such an authority could enable the Government to
      specify the design of tobacco products (to maximise harm reduction), to eliminate
      the marketing for profit of branded products, and to appropriately control the
      introduction of alternative nicotine delivery devices or less hazardous
      alternative tobacco products. As the authority could be funded through levies on
      the tobacco industry, it has the potential advantage of delivering major
      population health gains while costing the taxpayer nothing.

PMID- 15843835
TI  - A tribute: the contribution of the Otago University Medical School and its
      students in World War 1.

PMID- 15843836
TI  - Attitudes to, and knowledge of, secondhand smoke in New Zealand homes and cars.
AB  - AIMS: To review the evidence on knowledge and attitudes among the New Zealand
      public concerning secondhand smoke (SHS) and smoking in homes and cars. METHODS:
      A literature search for published and unpublished material relevant to New
      Zealand. RESULTS: While New Zealanders' knowledge about SHS effects has improved
      since 1989, with 90% or more of the adult population aware of a risk to health,
      this knowledge may be shallow. Wellington area surveys indicate that significant
      proportions of the population are not aware of both the major consequences of
      SHS, that is, strokes and heart disease. Survey data indicates increasing public
      support for smokefree homes during 1999-2003, particularly among Maori who showed
      a 68% increase in support during that period. In 2003, over 80% of New Zealand
      smokers indicated that people have a right to smokefree homes. However, these
      attitudes do not necessarily result in smokefree homes. Of those 14-15 year olds
      with at least one parent who smoked, less than 45% reported having a smokefree
      home. CONCLUSIONS: Improved tobacco control and increased investment in mass
      media campaigns on SHS issues are needed to strengthen healthy norms around
      smokefree homes and cars.

PMID- 15843837
TI  - Access to tobacco products by New Zealand youth.
AB  - AIMS: To describe the sources of cigarettes for under-age youth who had smoked in
      the previous month, the frequency of their purchases and the revenue generated.
      METHODS: A self-report questionnaire was administered to 3434 secondary school
      students from 82 schools, randomly selected using multi-stage cluster sampling.
      RESULTS: Over one-third of the students who smoked had purchased tobacco products
      from commercial sources in the month before the survey; most frequently from
      dairies and service stations. For more than one-third of smokers (35.7%), being
      younger than 18 years was not a barrier to purchasing tobacco products. During
      2002, the retail value of tobacco sales to those 14-16 years, alone, was
      estimated to be in excess of 18 million dollars, with around 12.5 million dollars
      of this going to the Government as taxes. CONCLUSIONS: Policies that restrict
      youth access to tobacco products can only be effective if they are rigorously
      enforced. Many young New Zealanders have no difficulty in purchasing tobacco
      products, thereby generating significant revenue. Total sales to all smokers
      under 18 years would be likely to exceed of 24 million dollars, with around 17
      million dollars in taxes. Current legislation and enforcement is not a sufficient
      deterrent to ensure retailer compliance with age restrictions. It would be
      appropriate to use at least some of the revenue from under-age sales to fund
      health promotion programmes to reduce tobacco smoking and other health
      compromising behaviours among youth. Nationally collated data on monitoring
      visits, prosecutions, and fines for under-age sales are currently not readily
      available, thereby limiting opportunities for evaluation.

PMID- 15843838
TI  - Chronic obstructive pulmonary disease (COPD): smoking remains the most important
      cause.

PMID- 15843839
TI  - Lung cancer in Maori: a neglected priority.

PMID- 15843840
TI  - Varying evolution of the New Zealand lung cancer epidemic by ethnicity and
      socioeconomic position (1981-1999).
AB  - AIM: Tobacco use and resultant health effects have been described as an epidemic
      that progresses through the population. This paper aims to describe and explain
      trends in lung cancer mortality by ethnicity and socioeconomic position in New
      Zealand between 1981-1999. METHODS: Cohort studies of the entire New Zealand
      population for 1981-84, 1986-89, 1991-94, and 1996-99 (linking census and
      mortality datasets) allowed direct determination of trends in lung mortality by
      income and education. For ethnicity, we used unlinked census and mortality data-
      but with correction factors applied for undercounting of Maori and Pacific
      deaths. RESULTS: Lung cancer mortality decreased in males and increased in
      females over the time period studied. In males, socioeconomic inequality
      persisted despite a decline in mortality in all socioeconomic groups. In females,
      a disproportionate increase in the mortality of lower socioeconomic groups
      compared to higher socioeconomic groups resulted in an increase in inequality.
      Divergent trends by ethnic group resulted in an increase in ethnic inequalities
      between 1981 and 1996 in both males and females. CONCLUSIONS: There are
      significant and growing ethnic and socioeconomic inequalities in lung cancer
      mortality in New Zealand. In the current absence of concerted public health
      action these inequalities will probably widen in future decades.

PMID- 15843841
TI  - The burden of death, disease, and disability due to alcohol in New Zealand.
AB  - AIM: To estimate the burden of death, disease, and disability attributable to
      alcohol consumption in New Zealand. METHODS: We applied the World Health
      Organization's comparative risk assessment methodology at country level;
      separately for Maori and non-Maori where possible. We combined the best estimates
      of alcohol consumption in the populations, with best estimates of alcohol-disease
      relationships from the international and, where available, national
      epidemiological literature, to calculate the proportions of alcohol-related
      conditions attributable to alcohol. RESULTS: We estimated that 3.9% of deaths in
      New Zealand in 2000 were attributable to alcohol consumption (approximately 1037
      deaths), and approximately 981 deaths were prevented by alcohol, resulting in a
      net loss of about 56 lives. As a consequence, 17,200 years of life were lost, but
      only 5,300 years of life gained; a net loss of almost 12,000 years of life. The
      burden was substantially higher for younger age groups, for men compared with
      women, and for Maori compared with non-Maori. Injury was the biggest contributing
      cause of death and years of life lost, while positive effects were largely due to
      reduced coronary disease mortality in elderly people. The impact of alcohol on
      these conditions depended on the pattern as well as volume of drinking. In a
      separate analysis that included estimates of morbidity, we calculated a net loss
      of 26,000 disability-adjusted life years (DALYs) due to alcohol in 2002, with 76%
      lost by men. Alcohol use disorders accounted for about half of all DALYs lost.
      CONCLUSIONS: Five main messages emerged from the analysis that can inform policy
      to reduce the health burden of alcohol: there are no health benefits of drinking
      alcohol before middle age; pattern of drinking is an important determinant of
      health effects; injuries are a major component of the alcohol burden; alcohol use
      disorders underlie many adverse effects; and the health impact of alcohol falls
      inequitably on Maori.

PMID- 15843842
TI  - Suspicious pulmonary nodules.

PMID- 15843843
TI  - Near death episode after exposure to toxic gases from liquid manure.

PMID- 15843844
TI  - Can Quit Practice: a comprehensive smoking cessation programme for the general
      practice team.
AB  - AIMS: To develop, implement, and evaluate a programme of training and support for
      smoking cessation provision in general practice. METHODS: The Can Quit Practice
      Programme was developed for delivery in general practices with a particular focus
      on the skills of the practice nurse (PN) in providing quit support. The Programme
      utilises the principles of brief intervention by the GP or PN followed by a
      systematic quit support programme delivered by trained practice nurses (quit
      advisors). Alternative implementation strategies and the provision of ongoing
      support and problem solving sessions were integral parts of the Programme. The
      evaluation used qualitative and quantitative methods to establish quit rates for
      participants enrolled in the Programme and explore the efficacy of programme
      delivery. RESULTS: The quit rates achieved by 85 smokers (from 14 general
      practices) enrolled in the Can Quit Practice Programme evaluation were; 25.9% at
      3 months; 22.4% at 6 months; and 20.0% at 9 months. Important components of
      successful implementation were: an autonomous role for PNs; well-managed practice
      procedures; adequate consultation time; and adequate funding for health
      promotion. CONCLUSION: Smoking cessation programmes can be successfully
      implemented and maintained within general practices as an integrated part of
      primary healthcare.

PMID- 15843846
TI  - Regarding 'Investigation for iron deficiency anaemia'.

PMID- 15843847
TI  - Screening for prostate cancer: a patient's view.

PMID- 15843848
TI  - Bariatric surgery in New Zealand.

PMID- 15843851
TI  - Severe acute respiratory syndrome epidemic in Taiwan, 2003.
AB  - In Taiwan, since the first case of severe acute respiratory syndrome (SARS) was
      identified on February 25, 2003, a total of 3032 cases of suspected or probable
      SARS were reported prior to July 5, 2003. Among these cases, 664 cases were
      classified as probable SARS based on the clinical case definitions and 346 had a
      positive result for the SARS-associated coronavirus (SARS-CoV). The epidemic in
      Taiwan could be divided into 2 distinct stages. In stage I (late-February to mid
      April) patients had traceable contact with infected patients or travel histories
      to known affected areas of SARS. By contrast, patients in stage II (mid-April to
      June) acquired infection via intra-hospital or inter-hospital transmission. The
      mortality rate directly attributable to SARS during the 2 stages of the outbreak
      in Taiwan was 11% (37 patients). Phylogenetic analysis of sequences of SARS-CoV
      strains in Taiwan and other countries showed that Taiwanese strains were closely
      related to those isolated from patients in Hong Kong and Guangdong. The
      nonspecific initial symptoms and signs of the illness, the absence of reliable
      diagnostic tests, as well as the initial lack of strict infection control
      measures in hospitals and effective national control policies contributed to the
      island-wide spread of the SARS epidemic in Taiwan. Development of an effective
      strategy to prepare for future outbreaks will require the implementation of an
      active coordinated clinical reporting system, international collaboration to
      identify cases in the early stage, development of laboratory tools for early
      diagnosis, a robust system of prepared isolation, and adequate quarantine
      facilities.

PMID- 15843852
TI  - Clinical and immunologic characteristics and therapeutic interventions in
      children born to human immunodeficiency virus-infected mothers in southern
      Taiwan.
AB  - Since the late 1990s, the epidemic of human immunodeficiency virus (HIV)
      infection in Taiwan has expanded dramatically. Pediatric HIV infection has also
      increased at an alarming pace. Nearly 40% of the HIV-infected children (<10
      years) contracted infection through mother-to-child transmission (MTCT). The aims
      of this study were to evaluate the effects of interventions to prevent MTCT of
      HIV infection, and to describe the clinical and immunologic characteristics of
      children born to HIV-seropositive mothers in southern Taiwan. From 1995 to 2003,
      an observational, longitudinal study of 8 children born to HIV-infected mothers
      was carried out at a tertiary care university hospital. The median age at
      enrollment was 0.4 years (range, 1 day-7.5 years), and the mean duration of
      follow-up was 2.7 years. Four mothers were immigrants from southeastern Asia. Due
      to antenatal diagnosis of maternal HIV infection, 3 children underwent
      interventions, including cesarean section, prophylactic use of zidovudine, and
      bottle-feeding in order to prevent vertical transmission. Five children were born
      without interventions because of delayed diagnosis of maternal HIV infection.
      During follow-up, 2 children were found to be HIV-infected and 6 were not
      infected. The rate of MTCT was lower among patients with interventions (0% vs
      40%). In HIV-exposed/non-infected children, the clinical and immunologic
      assessments were normal during follow-up. Both HIV-infected children progressed
      to the stage of acquired immunodeficiency syndrome. Early identification of HIV
      seropositive pregnant women, implementations to reduce vertical transmission, and
      introduction of antiretroviral therapy permit optimism in the prevention and
      treatment of pediatric HIV infection.

PMID- 15843853
TI  - Antitumor features of Bacillus oligonitrophilus KU-1 strain.
AB  - Chemotherapy and radiotherapy remain mostly palliative methods for metastatic
      cancer treatment. Limitations in efficacy and safety of established treatments
      continue to underline the need for improved treatments for malignancy. Results
      with some probiotics with antitumor activity have been promising. Here, we report
      that oral reception of Bacillus oligonitrophilus KU-1 resulted in the
      prolongation of lives in cancer patients with terminal prognosis and
      stabilization of cancer growth. The theoretical basis for the phenomena observed
      is discussed.

PMID- 15843854
TI  - Clinical and genetic analysis of invasive and non-invasive group A streptococcal
      infections in central Taiwan.
AB  - To evaluate the clinical, bacteriologic, and genetic relatedness between invasive
      and non-invasive infections caused by group A Streptococcus (GAS), we
      retrospectively analyzed the GAS isolates in our hospital from the past decade. A
      total of 70 GAS-infected cases were enrolled in our study from the period 1993 to
      2002. Twenty one cases had invasive disease, and 49 were non-invasive. Their
      medical records were reviewed, and demographic data were collected for analysis.
      Antimicrobial susceptibility testing was conducted according to the National
      Committee for Clinical Laboratory Standards for Streptococcus spp. Isolates were
      subjected to chromosomal SmaI (Invitrogen) digestion of pulsed-field gel
      electrophoresis (PFGE), and emm typing was also performed. The mean age of the
      invasive group was 41.1 +/- 22.4 years compared with 13.0 +/- 16.6 years for the
      non-invasive group (p<0.05). Eighty one percent of the invasive group had
      underlying diseases. Diabetes and malignancy were the 2 most common medical
      conditions. All isolates were susceptible to penicillin. The resistance rate was
      42.8% and 55.1% for erythromycin in the invasive and non-invasive groups,
      respectively. A total of 51 different PFGE types were identified among the GAS
      isolates without particular genotypes. Serotype M12 was the most common one
      (28.4%), followed by M4 (19.4%). Our study demonstrated that the patients in the
      invasive group were older, with more underlying diseases, and with a higher
      mortality rate. Antimicrobial susceptibility of the isolates was the same in both
      groups. There was no epidemic strain, nor did PFGE reveal a more invasive clone.

PMID- 15843855
TI  - Infections of cefotaxime-resistant and cefmetazole-susceptible Escherichia coli
      and Klebsiella pneumoniae in children.
AB  - A search of the computerized database at the National Taiwan University Hospital
      was made for cefotaxime-resistant and cefmetazole-susceptible isolates of
      Escherichia coli and Klebsiella pneumoniae (which may be extended-spectrum beta
      lactamase-producing strains) in pediatric wards and intensive care units between
      1999 and 2001. Fourteen infectious episodes attributed only to study bacteria
      were identified, including 7 episodes of bacteremia. Nine patients (64.3%) had
      underlying medical conditions: 3 were premature babies, 3 were immunodeficient, 2
      had malignancy, and 2 had a congenital heart disease with active heart failure
      even after surgery. Among the 7 patients with bacteremias, 5 may be catheter
      related; 6 were treated with carbapenems and 1 was treated with cefmetazole
      successfully, with or without the removal of the catheter. Before the acquisition
      of the infection, a history of stay in an intensive care unit within 4 weeks was
      noted in 10 cases (71.4%); a history of use of extended-spectrum cephalosporins
      within 4 weeks was also noted in 6 cases (42.9%). Cefmetazole, with or without an
      aminoglycoside, was clinically effective in 6 cases (42.8%). Except for 1 episode
      of pneumonia that ended in mortality, all of the infectious episodes were
      successfully treated. The mortality rate was 7.1%.

PMID- 15843856
TI  - Chlamydial pneumonia in children requiring hospitalization: effect of mixed
      infection on clinical outcome.
AB  - The etiology of community-acquired pneumonia (CAP) in a children's hospital was
      studied among 209 previously healthy children treated from August 1, 2001 to July
      31, 2002. A total of 26 children (12.4%) with a diagnosis of chlamydial infection
      were included in this study. The diagnosis of chlamydial infection was based on
      either a positive immunofluorescent assay result for chlamydial antigen in
      sputum, or positive serologic results for immunoglobulin M (IgM), an IgG titer
      >/=1:640 or a 4-fold rise in IgG titer by microimmunofluorescence test. Fourteen
      patients (53.8%) were female and 20 (76.9%) were less than 5 years of age. The
      onset of infection occurred between August and January in 21 cases (80.7%).
      Twenty one patients (80.8%) had other pathogens identified. Fever and cough were
      the most common presenting symptoms. The signs and symptoms were similar for the
      children with and without coinfection except for tachypnea and wheezing sound,
      which were significantly more common in patients with mixed infection. None of
      the laboratory parameters seemed to be specific for chlamydial infection;
      however, serum C-reactive protein level was significantly higher in cases with
      mixed infection. Among the 26 children, 12 (46.2%) needed respiratory therapy,
      and most of them (91.7%, 11/12) had coinfection. Two patients (7.7%) with mixed
      infection were admitted to the pediatric intensive care unit. One had lobar
      pneumonia with pleural effusion and the other had necrotizing pneumonia requiring
      surgical intervention. None of the patients died. In conclusion, Chlamydia sp.
      was identified in 12.4% of children with CAP in this series, and mixed infections
      were common (80.8%) among these patients. The clinical course of chlamydial
      pneumonia was not serious in most patients, but alertness is needed to the
      possibility of developing severe pneumonia in cases with bacterial coinfection.

PMID- 15843857
TI  - The relationship of air pollution to the prevalence of allergic diseases in
      Taichung and Chu-Shan in 2002.
AB  - This study was conducted in order to determine the relationship between air
      pollution and the varying prevalence of allergic diseases in the city of Taichung
      and the rural town of Chu-Shan. We used questionnaires to screen children aged
      from 7 to 15 years in Taichung and Chu-Shan and compared the results from these 2
      areas with the factors related to air pollution. The study included 11,580
      children in Taichung and 2621 children in Chu-Shan. In Taichung, the prevalence
      of asthma was 7.0%, of allergic rhinitis 27.6% and of atopic dermatitis 3.4%. In
      Chu-Shan, the prevalence of asthma was 5.6%, of allergic rhinitis 21.8% and of
      atopic dermatitis 3.3%. We also collected data on the concentration of air
      pollutants in the 2 areas over a 1-year period from January to December 2001 and
      compared the average annual concentrations of various pollutants. Compared with
      Chu-Shan, Taichung had higher air concentrations of nitric oxide (NO; 11.47 +/-
      4.75 vs 5.07 +/- 2.81 ppb), carbon monoxide (CO; 0.78 +/- 0.19 vs 0.59 +/- 0.12
      ppm), nitrogen dioxide (NO(2); 24.99 +/- 6.8 vs 21.45 +/- 7.87 ppb) and sulfur
      dioxide (SO(2); 2.58 +/- 1.0 vs 2.44 +/- 0.88 ppb). Student's t test results
      showed that CO and NO were related significantly to the prevalence of allergic
      disease (p<0.005). The prevalence of both asthma and allergic rhinitis is higher
      in Taichung than in Chu-Shan, a finding that could be related to higher levels of
      some air pollutants in the urban location.

PMID- 15843858
TI  - Predictors of mortality in Acinetobacter baumannii bacteremia.
AB  - This study retrospectively investigated 149 episodes of Acinetobacter baumannii
      bacteremia which occurred during a 41-month period from September 1997 to January
      2001. Bacteremia was nosocomial in 139 (93%) of the episodes and community
      acquired in 10 (7%). Thirty three deaths (22.1%) were attributed to these
      episodes of A. baumannii bacteremia. The mean age of survivors was younger than
      that of patients who died of bacteremia (60.4 +/- 19.9 vs 67.1 +/- 17.4) but this
      result was not significant on univariate analysis (p=0.084). Previous intensive
      care unit stay was longer among survivors than among patients who died of
      bacteremia (9.5 vs 18 days, p=0.048). Factors associated with mortality included
      immunosuppression (p=0.019), shock (p=0.002), recent surgery (p=0.008), invasive
      procedures such as central venous catheterization (p=0.002), urinary
      catheterization (p=0.012), placement of a nasogastric tube (p<0.001), pulmonary
      catheterization (p=0.015), and mechanical ventilation (p=0.035). The number of
      underlying conditions (p=0.015) and invasive procedures (p<0.001) were positively
      correlated with mortality. Mortality was significantly associated with lower
      platelet count (p=0.001) and lower serum albumin concentration (p=0.005).
      Patients with catheter-related bacteremia had a high survival rate (96.2%), while
      survival rate was low in patients with infection originating from the respiratory
      tract (60.8%). Susceptibility testing by agar dilution test indicated that
      imipenem was the most effective antibiotic, followed by cefepime and
      ciprofloxacin. The mortality rate was lower in patients who received 1 or more
      antibiotics to which the isolates were susceptible, but this difference was not
      significant (p=0.197). On multivariate analysis, factors that independently
      correlated with mortality were increased age (p=0.003), immunosuppressive status
      (p=0.001), recent surgery (p=0.002), acute respiratory failure (p=0.004), acute
      renal failure (p=0.009) and septic shock (p<0.001). These findings highlight the
      importance of a treatment strategy based on risk stratification among patients
      with A. baumannii bacteremia.

PMID- 15843859
TI  - Gram stain as a relapse predictor of bacterial vaginosis after metronidazole
      treatment.
AB  - Bacterial vaginosis is the most prevalent disease of the female genital tract. In
      spite of various effective antibiotics in the treatment of bacterial vaginosis,
      its high relapse rate is a common problem. Bacterial species causing bacterial
      vaginosis are generally unable to be cultured by conventional methods. It is
      impractical and inadequate to use culture methods to guide initial treatment.
      Gram stain of vaginal secretion is a practical tool to establish the diagnosis of
      bacterial vaginosis. We enrolled 78 cases of Gram stain-proven bacterial
      vaginosis and tried to use Gram stain as a predictor of relapse after 1 week of
      treatment with metronidazole. Possible predictive factors for relapse in Gram
      stain were analyzed, including absence of large Gram-positive rods, presence of
      small Gram-negative rods, small Gram-variable rods, curved Gram-variable rods, or
      Gram-positive cocci. Gram stain was repeated immediately after treatment, and at
      1 month and 3 months after treatment. All cases showed beneficial clinical effect
      after metronidazole treatment. Eighteen cases (23.1%) relapsed during the follow
      up period. All 16 cases with significant Gram-positive cocci in pretreatment
      smears relapsed after metronidazole treatment. Presence of small Gram-negative
      rods, small Gram-variable rods, and curved Gram-variable rods, or absence of
      large Gram-positive rods did not predict relapse. Gram-positive cocci in
      pretreatment smear was a good predictor of relapse after metronidazole treatment.

PMID- 15843860
TI  - Transient hypogammaglobulinemia of infancy presenting as Staphylococcus aureus
      sepsis with deep neck infection.
AB  - Transient hypogammaglobulinemia of infancy (THI) is characterized by a
      prolongation and accentuation of the physiologic hypogammaglobulinemia normally
      occurring during the first 3 to 6 months of life and recovers spontaneously
      between 18 and 36 months of age. Infants with THI may remain asymptomatic or
      develop recurrent sinopulmonary infections, but severe or life-threatening
      infections are rare. We report a case of THI in a previously healthy 1-year-old
      girl with Staphylococcus aureus sepsis who subsequently developed deep neck
      infection confirmed by magnetic resonance imaging. Intravenous oxacillin was
      administered for 21 days and she recovered completely. Immunologic studies were
      normal except for decreased immunoglobulin G levels. Under the impression of
      hypogammaglobulinemia with severe infection she received regular intravenous
      immunoglobulins (IVIG) replacement therapy every 4 weeks. One year later, the
      immunoglobulin concentrations had returned to the normal range even though IVIG
      had been discontinued for 4 months. This case report highlights the possibility
      of severe infection in THI, a disease which usually has a benign clinical course.
      As the diagnosis of THI can only be made with certainty in retrospect, long-term
      follow-up of clinical and immune system status is necessary.

PMID- 15843861
TI  - Interstitial lung disease and xerostomia as initial manifestations in a patient
      with human immunodeficiency virus infection.
AB  - A 56-year-old human immunodeficiency virus (HIV)-infected man presented with
      progressive interstitial lung disease (ILD) and lymphocyte infiltration of the
      salivary glands which mimicked autoimmune disease. Pneumonia, which was very
      likely caused by Pneumocystis carinii, developed after 3 courses of monthly
      methylprednisolone pulse therapy for ILD. Both enzyme immunoassay and Western
      blot analysis confirmed the HIV infection. After antibiotic treatment, the
      pneumonia gradually resolved. Autoimmune manifestations such as ILD and
      xerostomia may be initial presentations of HIV infection. Immunosuppressive drugs
      must be used cautiously in these patients. Screening for HIV is mandatory in the
      differential diagnosis of patients with ILD or xerostomia.

PMID- 15843862
TI  - Methylprednisolone pulse therapy for massive lymphadenopathy in a child with
      intravenous immunoglobulin-resistant Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute febrile multi-system vasculitis of unknown
      etiology. The diagnosis is based on clinical features. We describe a case of
      intravenous immunoglobulins (IVIG)-resistant KD presenting with persistent fever
      and massive cervical lymphadenopathy associated with mild respiratory distress.
      The symptoms resolved after methylprednisolone pulse therapy. High-dose pulse
      steroid may be an alternative therapeutic option in KD which presents with
      possible life-threatening complications or failure to respond to high-dose IVIG
      infusion.

PMID- 15843863
TI  - Karyomorphology of Maianthemum sensu lato (Polygonatae, Ruscaceae).
AB  - We report results of karyotype analyses using nine species of Maianthemum from
      China. The species, except M. atropurpureum (with 2n=72), had 2n=36, and the
      results support the earlier suggestion that Maianthemum has x=18 with 2n=36 in
      most species. The species examined, however, showed marked differences in
      karyotype, particularly in the numbers of metacentric, submetacentric, and
      acrocentric chromosomes as well as in the number of satellites. In addition, we
      distinguished three different modes based on the number of clear gaps in
      chromosome length variation: unimodal, bimodal, and trimodal. The unimodal
      variation (with no gap) was found in M. dahuricum and M. atropurpureum, the
      bimodal variation (with one gap) in M. tatsienense, and the trimodal variation
      (with two gaps) in M. bifolium, M. forrestii, M. japonicum, M. henryi, M.
      purpureum, and M. lichiangense. In the trimodal variation, the positions of the
      two gaps may differ from species to species. In addition, the frequency of
      acrocentric chromosomes per complement was generally higher in the trimodal
      variation than in the unimodal and bimodal variations. Results of our analyses,
      which had not been clearly presented prior to this, may provide a better
      understanding of species evolution in the tribe Polygonatae.

PMID- 15843865
TI  - Lead tolerance and accumulation in the gametophytes of the fern Athyrium
      yokoscense.
AB  - The fern Athyrium yokoscense is known to be highly tolerant to lead toxicity, and
      is a lead hyperaccumulator that can accumulate over 1,000 microg g(-1) of lead in
      its dry matter. In this work, we examined whether the gametophytic generation of
      A. yokoscense also resists lead toxicity like the sporophytic generation. Spore
      germination in A. yokoscense was more tolerant to Pb2+, compared to that in other
      fern species, such as Pteridium aquilinum, Lygodium japonicum and Pteris vittata.
      In addition, the early gametophyte development of A. yokoscense was not much
      affected by 10 microM Pb2+, as evaluated from the prothallial growth and rhizoid
      development. We also showed that Athyrium gametophytes could accumulate more than
      10,000 microg g(-1) of lead, and that the lead was localized in the cytosol and
      vacuole of rhizoidal cells, as determined by a transmission electron micrograph.
      These results indicate that Athyrium gametophytes have the ability to accumulate
      lead in the rhizoids. Furthermore, the gametophytes were found to include a large
      amount of proanthocyanidins (condensed tannins). Because proanthocyanidins have a
      latent ability to complex with lead ions, the possible roles of proanthocyanidins
      in the lead tolerance and accumulation of Athyrium gametophytes are discussed.

PMID- 15843864
TI  - Nucleolonema as a fundamental substructure of the nucleolus.
AB  - The nucleolus is the most obvious structure in the eukaryotic nucleus. It is
      known to be a ribosome-producing apparatus where ribosomal (r) DNA is transcribed
      and the primary rRNA transcripts are processed to produce three of the four rRNA
      species. Electron microscopy has shown that the nucleolus consists of three major
      components, a dense fibrillar component (DFC), a granular component (GC) and a
      fibrillar center (FC). The DFC and FCs are integrated into a fundamental
      nucleolar substructure called the nucleolonema. The DFC corresponds to the matrix
      of the nucleolonema, and the FC is an electron microscopic counterpart of
      argyrophobic lacunae localized in the nucleolonema. The spherical FCs are
      intermittently arranged along the length of the nucleolonema in actively growing
      cells but are fused with each other to form tubular FCs when rDNA transcription
      is hampered. The RNase-gold complex does not bind to the FC but to the DFC and
      the GC, suggesting that rDNA transcription does not occur in the FC although both
      fluorescence in situ hybridization (FISH) and electron microscopic in situ
      hybridization reveal that the rDNA is specifically localized in the FCs.
      Immunogold-labeling after bromo-UTP (BrUTP) incorporation shows that rDNA
      transcription takes place in the boundary region between the FC and the DFC, and
      primary rRNA transcripts are expected to be processed outward within the DFC.
      Data have accumulated suggesting that the nucleolonema is a fundamental
      substructure of the nucleolus, and its skeleton is the tandem arrangement of the
      FCs, which are resting harbors or storages of rDNA. This paper proposes that the
      transversal structural organization of the nucleolonema is centrifugally built up
      by several structural and functional domains: condensed and/or loosened rDNA,
      rDNA transcription zone, and transcript processing and ribosome assembly zones.

PMID- 15843866
TI  - A peptide preparation protects cells in organotypic brain slices against cell
      death after glutamate intoxication.
AB  - Cerebrolysin has been shown to have neurotrophic and neuroprotective potential
      similar to NGF or BDNF. In the present study organotypic brain slices were
      utilized to determine the neuroprotective effects of Cerebrolysin, in a glutamate
      lesion paradigm mimicking a key event in ischemia. The study focused on the
      effects of Cerebrolysin on both necrotic and apoptotic cell death. Two specific
      DNA intercalating dyes were used to distinguish the type of cell death. The drug
      effect was evaluated both microscopically and quantitatively before, 24 hours
      after and then again 8 days after the lesion. Cerebrolysin was added either
      before and after the lesion or after the lesion only. The most pronounced effect
      was seen with the drug added both prior to and after the glutamate lesioning. A
      treatment after the lesion only also counteracted necrosis and apoptosis. The
      results render the drug relevant for treating acute as well as chronic
      neurodegenerative diseases.

PMID- 15843868
TI  - Effects of blockade of glutamate NMDA receptors or of NO synthase on the
      development or the expression of associative or non-associative sensitization to
      locomotor activation by morphine.
AB  - The sensitization to the pharmacological actions of morphine is probably a
      critical factor in the addictive properties of this drug. A discrimination
      between associative and non-associative type of sensitization might be relevant
      for possible differences in drug effects on sensitization phenomena. Furthermore,
      blockade of NMDA receptors might lead to an inhibition of NO-synthesis, and,
      accordingly, both of these effects might influence sensitization phenomena in a
      similar way. Male Wistar rats were sensitized to morphine by administrations of 3
      mg/kg of morphine i.p. on day 1, 3, 5, and 7 and saline on days 2, 4, and 6. In
      part of the animals, the administration of morphine was performed in association
      with conditional stimuli, CS (test cage plus an auditory and an olfactory
      stimulus), in the other part not (pseudoconditioned, PCS). On day 17, the
      sensitization was more pronounced in the CS than the PCS group. The effects of
      dizocilpine (MK-801; 0.1 mg/kg i.p.), a blocker of NMDA glutamate receptors, or
      of L-NAME (N(G)-nitro-L-arginine methylester; 10 mg/kg i.p.), a non-specific
      inhibitor of NO synthase and the effect of N(omega)-propyl-L-arginine (20 mg/kg
      i.p.), a specific inhibitor of neuronal NO synthase, on expression or development
      of sensitization to morphine was studied. Neither MK-801 nor L-NAME influenced
      the development of associative and non-associative behavioural sensitization to
      morphine. The expression of sensitization to morphine was not influenced by MK
      801. L-NAME inhibited the expression of associative, but not of non-associative
      sensitization. Surprisingly, inhibition of neuronal NO synthase, did not
      influence the expression of associative sensitization. We suggest that NMDA
      receptors were not involved in development or expression of both types of
      sensitization. Furthermore, the manifestation of the associative, but not the non
      associative sensitization to morphine appeared to be dependent on a type of NO
      synthase, which is not the neuronal NO synthase, but probably the inducible NOS.

PMID- 15843867
TI  - N-Propargylamine protects SH-SY5Y cells from apoptosis induced by an endogenous
      neurotoxin, N-methyl(R)salsolinol, through stabilization of mitochondrial
      membrane and induction of anti-apoptotic Bcl-2.
AB  - Propargylamine derivatives, rasagiline and (-)deprenyl, are anti-Parkinson agents
      and protect neurons from cell death as shown by in vivo and in vitro experiments.
      The studies on the chemical structure-activity relationship proved that the
      propargyl moiety is essentially required for the neuroprotective function. In
      this paper, neuroprotective activity of free N-propargylamine was studied using
      SH-SY5Y cells expressing only type A monoamine oxidase (MAO) against apoptosis
      induced by an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol. N
      Propargylamine prevented apoptosis, whereas N-methylpropargylamine and
      propiolaldehyde did not. N-Propargylamine stabilized mitochondrial membrane
      potential and induced anti-apoptotic Bcl-2 at 1 microM-10 nM. N-Propargylamine
      inhibited MAO-A in competition to substrate with the apparent K(i) value of 28
      microM, which was significantly higher than the concentration required for
      neuroprotection. It indicates that MAO inhibition is not prerequisite for the
      protective function of N-propargylamine. The anti-apoptotic function of N
      propargylamine is discussed in terms of neuroprotection by propargylamines in
      neurodegenerative diseases, including Parkinson's disease.

PMID- 15843869
TI  - Time- and dose-dependent effects of corticotropin releasing factor on cerebral
      glucose metabolism in rats.
AB  - The time course and the relation to dose of locomotor activity and of the
      regional cerebral metabolic rates for glucose (rCMRglc) were measured in freely
      moving Sprague-Dawley rats after intracerebroventricular administration of ovine
      corticotropin releasing factor (oCRF). Motor activity was determined using a
      familiar photocage cell. rCMRglc was measured, using the quantitative
      autoradiographic [(14)C]2-deoxyglucose procedure, in 73 brain regions at 10, 30,
      90 and 180 min after administration of oCRF 10 microg and at 90 min after oCRF
      0.1, 1 and 100 microg. oCRF 10 microg increased motor activity in a sustained
      fashion and increased rCMRglc with different time courses throughout brain
      regions. In cerebellar regions rCMRglc increases peaked at 90 min and were
      sustained up to 180 min. In non-cerebellar regions rCMRglc increases peaked at 90
      min but declined thereafter. At lower doses (0.1 and 1 microg) oCRF increased
      rCMRglc in fewer brain regions (1 and 5 regions affected, average increases 1%
      and 7%) including cerebellar areas and brainstem sensory nuclei and decreased
      rCMRglc in medial prefrontal cortex. At the highest dose (100 microg) oCRF
      induced large and widespread rCMRglc increases in cerebellar, brainstem,
      hypothalamic, limbic and neocortical areas (40 brain regions affected, average
      increase 32%). The findings indicate that cerebellar areas and brainstem nuclei
      are highly sensitive to oCRF and may mediate oCRF autonomic and behavioral
      effects.

PMID- 15843870
TI  - No association with the calcineurin A gamma subunit gene (PPP3CC) haplotype to
      Japanese schizophrenia.
AB  - Calcineurin, one of the serine/threonine protein phosphatase, comprises more than
      1% of the total protein content in brain. This evidence points towards important
      roles of calcineurin in neural function. Miyakawa et al. reported that forebrain
      specific calcineurin knockout mice showed the behavioral abnormalities that are
      often observed in schizophrenia patients. Based on this evidence, they suggested
      that calcineurin dysfunction could be involved in schizophrenia pathogenesis.
      Thereafter this report, Gerber et al. performed transmission disequilibrium test
      (TDT) studies and showed an evidence for a nominally significant over
      transmission of a common haplotype of the human calcineurin A gamma subunit gene
      (PPP3CC). We performed association analysis of PPP3CC in Japanese sample of 457
      schizophrenia cases and 429 controls. To our regret, we could not confirm the
      association with Japanese schizophrenia to PPP3CC including core at-risk
      haplotype. Our result suggests that PPP3CC may not play a major role in Japanese
      schizophrenia.

PMID- 15843871
TI  - Epigenetics and biliary cancer: promise and pitfalls.

PMID- 15843872
TI  - Cytological analysis of peritoneal washings: now part of the standard
      preoperative staging evaluation for patients with resectable gastric cancer?

PMID- 15843873
TI  - The emergence of modern cancer immunotherapy.

PMID- 15843878
TI  - Andropause: is the emperor wearing any clothes?

PMID- 15843879
TI  - Men's aging and sexual disorders: an update on diagnosis and treatment.

PMID- 15843880
TI  - The Women's Health Initiative study: perspectives and implications for clinical
      practice.

PMID- 15843881
TI  - Frailty and hormones.

PMID- 15843882
TI  - Neuroendocrine effects on mood.

PMID- 15843883
TI  - Diabetic neuropathy in older adults.

PMID- 15843884
TI  - Weight loss in older adults.

PMID- 15843885
TI  - Adaptations to aerobic and resistance exercise in the elderly.

PMID- 15843886
TI  - Thyroid and aging.

PMID- 15843887
TI  - Cell death suppression by cytomegaloviruses.
AB  - Cytomegaloviruses (CMVs), a subset of betaherpesviruses, employ multiple
      strategies to suppress apoptosis in infected cells and thus to delay their death.
      Human cytomegalovirus (HCMV) encodes at least two proteins that directly
      interfere with the apoptotic signaling pathways, viral inhibitor of caspase-8
      induced apoptosis vICA (pUL36), and mitochondria-localized inhibitor of apoptosis
      vMIA (pUL37 x 1). vICA associates with pro-caspase-8 and appears to block its
      recruitment to the death-inducing signaling complex (DISC), a step preceding
      caspase-8 activation. vMIA binds and sequesters Bax at mitochondria, and
      interferes with BH3-only-death-factor/Bax-complex-mediated permeabilization of
      mitochondria. vMIA does not seem to either interact with Bak, a close structural
      and functional homologue of Bax, or to suppress Bak-mediated permeabilization of
      mitochondria and Bak-mediated apoptosis. All sequenced betaherpesviruses,
      including CMVs, encode close homologues of vICA, and those vICA homologues that
      have been tested, were found to be functional cell death suppressors. Overt
      sequence homologues of vMIA were found only in the genomes of primate CMVs, but
      recent observations made with murine CMV (MCMV) indicate that non-primate CMVs
      may also encode a cell death suppressor functionally resembling vMIA. The exact
      physiological roles and relative contributions of vMIA and vICA in suppressing
      death of CMV-infected cells in vivo have not been elucidated. There is strong
      evidence that the cell death suppressing function of vMIA is indispensable, and
      that vICA is dispensable for replication of HCMV. In addition to suppressed
      caspase-8 activation and sequestered Bax, CMV-infected cells display several
      other phenomena, less well characterized, that may diminish, directly or
      indirectly the extent of cell death.

PMID- 15843888
TI  - On the role of galectin-3 in cancer apoptosis.
AB  - Galectin-3, a member of the beta-galactoside-binding gene family, is a
      multifunctional protein implicated in a variety of biological functions,
      including tumor cell adhesion, proliferation, differentiation, angiogenesis,
      cancer progression and metastasis. Recent studies revealed that intracellular
      galectin-3 exhibits the activity to suppress drug induced apoptosis and anoikis
      (apoptosis induced by the loss of cell anchorage) that contribute to cell
      survival. Resistance to apoptosis is essential for cancer cell survival and plays
      a role in tumor progression. Conversely, it was recently shown that tumor cells'
      secreted galectin-3 induces T-cells' apoptosis, thus playing a role in the immune
      escape mechanism during tumor progression through induction of apoptosis of
      cancer-infiltrating T-cells. This review summarizes recent evidences on the role
      of galectin-3 as an anti-apoptotic and/or pro-apoptotic factor in various cell
      types and discusses the recent understanding of the molecular mechanisms of
      galectin-3 role in apoptosis. We also suggest potential directions for further
      analyses of this multifunctional protein.

PMID- 15843889
TI  - Constitutive presence of cytochrome c in the cytosol of a chemoresistant leukemic
      cell line.
AB  - The release of holocytochrome c (cyt c) from mitochondria into the cytosol is
      reportedly a landmark of the execution phase of apoptosis. As shown here, the P
      glycoprotein- (P-gp) expressing K562/ADR cell line (but not the parental K562
      cell line) exhibits both cytosolic and mitochondrial cyt c in the absence of any
      signs of apoptosis. K562/ADR cells were found to be relatively resistant to a
      variety of different inducers of apoptosis, and blocking the P-gp did not reverse
      this resistance. The release of cyt c in non-apoptotic K562/ADR cells was not
      accompanied by that of any other mitochondrial apoptogenic protein, such as AIF
      or Smac/DIABLO, and was inhibited by Bcl-2 over expression. In addition, using a
      cell-free system, we show that mitochondria isolated from K562/ADR cells
      spontaneously released cyt c. These data suggest that cyt c release may be
      compatible with the preservation of mitochondrial integrity and function, as well
      as cell proliferation.

PMID- 15843890
TI  - Smac/DIABLO and cytochrome c are released from mitochondria through a similar
      mechanism during UV-induced apoptosis.
AB  - During apoptosis, a key event is the release of Smac/DIABLO (an inhibitor of
      XIAP) and cytochrome c (Cyt-c, an activator of caspase-9) from mitochondria to
      cytosol. It was not clear, however, whether the releasing mechanisms of these two
      proteins are the same. Using a combination of single living-cell analysis and
      immunostaining techniques, we investigated the dynamic process of Smac and Cyt-c
      release during UV-induced apoptosis in HeLa cells. We found that YFP-labeled Smac
      and GFP-labeled Cyt-c were released from mitochondria in the same time window,
      which coincided with the mitochondrial membrane potential depolarization.
      Furthermore, using immunostaining, we found that the endogenous Smac and Cyt-c
      were always released together within an individual cell. Finally, when cells were
      pre-treated with caspase inhibitor (z-VAD-fmk) to block caspase activation, the
      process of Smac release, like that of Cyt-c, was not affected. This was true for
      both YFP-labeled Smac and endogenous Smac. These results suggest that in HeLa
      cells, both Smac and Cyt-c are released from mitochondria during UV-induced
      apoptosis through the same permeability transition mechanism, which we believe is
      triggered by the aggregation of Bax in the outer mitochondrial membrane to form
      lipid-protein complex.

PMID- 15843891
TI  - Nuclear BAG-1 expression inhibits apoptosis in colorectal adenoma-derived
      epithelial cells.
AB  - BAG-1 is an anti-apoptotic protein that is frequently deregulated in a variety of
      malignancies including colorectal cancer. There are three isoforms: BAG-1L is
      located in the nucleus, BAG-1M and BAG-1S are located both in the nucleus and the
      cytoplasm. In colon cancer, the expression of nuclear BAG-1 is associated with
      poorer prognosis and is potentially a useful predictive factor for distant
      metastasis. However, the function of BAG-1 in colonic epithelial cells has not
      been studied. Having previously shown a predominant nuclear localisation of BAG-1
      in adenoma-derived cell lines, we wanted to determine the function of nuclear BAG
      1 in these non-tumourigenic cells, to identify whether nuclear BAG-1 was
      implicated in tumour progression in the colon. In the current report we
      established that nuclear BAG-1 inhibits apoptosis in a colorectal adenoma-derived
      cell line. We demonstrate that apoptosis induced by gamma-radiation or the
      vitamin D analogue EB1089 in the non-tumourigenic human colorectal adenoma
      derived S/RG/C2 cell line, was preceded by a decrease in nuclear and an increase
      in cytoplasmic BAG-1 expression. This change in subcellular localisation of BAG-1
      was due to the redistribution of the BAG-1M isoform. In addition, we have shown
      that the maintenance of high nuclear BAG-1 through enforced expression of the
      nuclear localised BAG-1L isoform enhanced cellular survival after gamma-radiation
      or exposure to EB1089. Furthermore the expression of cytoplasmic BAG-1S isoform
      fused with a nuclear localisation signal protected against gamma-radiation
      induced apoptosis. This demonstrates that nuclear localisation of the BAG-1
      protein confers a survival advantage in colorectal adenoma-derived cells and that
      nuclear BAG-1 could potentially be an important survival factor in colorectal
      carcinogenesis.

PMID- 15843892
TI  - Procaspase-2S inhibits procaspase-3 processing and activation, preventing ROCK-1
      mediated apoptotic blebbing and body formation in human B lymphoma Namalwa cells.
AB  - Procaspase-2S has been reported to selectively prevent membrane blebbing and
      apoptotic body formation in human monocytic-like leukemic U937 cells after
      etoposide (VP-16) treatment (Droin et al., Oncogene 20. 260-269, 2001). Here, we
      show that procaspase-2S overexpressed in human B lymphoma Namalwa cells inhibits
      procaspase-3 processing and activation, preventing cleavage and activation of Rho
      GTPase-associated ROCK-1 kinase. Failure of ROCK-1 activation in Namalwa cells
      correlates with a sustained delay in the appearance of membrane blebbing and
      apoptotic body formation after VP-16 treatment. Reciprocal coimmunoprecipitation
      experiments indicate that procaspase-2S binds to procaspase-3, but not procaspase
      2L and -9 in untreated and VP-16-treated Namalwa cells. These data suggest that
      procaspase-2S-mediated anti-apoptotic effects are associated with inhibition of
      the processing and activation of procaspase-3 in VP-16-treated cells.

PMID- 15843893
TI  - Structure-based design of an agonistic peptide targeting Fas.
AB  - A small agonistic peptide FRAP-4 (WEWT, Fas reactive peptide-4) that binds to the
      human Fas molecule was discovered using our computer screening strategy named the
      Amino acid Complement Wave (ACW) method, which is based on the complementarities
      of interacting amino acids between comprehensive testing peptides and a target
      protein surface pocket. In silico docking studies demonstrated the specific
      interaction of FRAP-4 with the main Fas ligand (FasL) binding domain in the Fas
      molecule. An octamer of this peptide produced by carboxyl terminal linkages of
      polylysine branches (MAP), (FRAP-4)8-MAP, effectively induced apoptosis in human
      ovarian cancer cell line NOS4 cells that was associated with the activation of
      caspases-8, -9 and -3, and the cleavage of PARP. Alanine substitution of the N
      terminal W in FRAP-4 resulted in complete loss of FasL-mimetic action of (FRAP
      4)8-MAP, suggesting that the aromatic functionality at the N-terminal position W
      appears to play an essentially important role in Fas binding ability. These
      observations indicate that the FasL-mimetic peptide should serve as an excellent
      starting point for the design of effective compounds with FasL-mimetic activity.
      Furthermore, the ACW method for the structure-based design of optimized small
      peptides against receptor molecules such as Fas could open new avenues for the
      development of peptide mimetic and nonpeptidic organic forms to generate novel
      effective pharmaceuticals.

PMID- 15843894
TI  - Analysis of gene expression in apoptosis of human lymphoma U937 cells induced by
      heat shock and the effects of alpha-phenyl N-tert-butylnitrone (PBN) and its
      derivatives.
AB  - Hyperthermia, a modality of cancer therapy, has been known as a stress to induce
      apoptosis. However, the molecular mechanism of heat shock-induced apoptosis,
      especially on roles of intracellular oxidative stress, is not fully understood.
      First, when human lymphoma U937 cells were treated with heat shock (44 degrees C,
      30 min), the fraction of apoptosis, revealed by phosphatidylserine
      externalization, increased gradually and peaked at 6 hr after the treatment. In
      contrast, intracellular superoxide formation increased early during the heat
      shock treatment and peaked at 30 min after the treatment. When the cells were
      treated with heat shock in the presence of alpha -phenyl-N-tert-butylnitrone
      (PBN) and its derivatives, which are potent antioxidants, the DNA fragmentation
      was inhibited in an order according to the agents' hydrophobicity. PBN showing
      the highest inhibitory effects suppressed not only intracellular superoxide
      formation but also various apoptosis indicators. cDNA microarray was employed to
      analyze gene expression associated with heat shock-induced apoptosis, and the
      time-course microarray analysis revealed 5 groups showing changes in their
      pattern of gene expression. Among these genes, c-jun mRNA expression showed more
      than 40 fold increase 2 hr after heat treatment. The expression level of c-jun
      mRNA verified by quantitative real-time PCR was about 20 fold increase, and c-jun
      expression was similarly suppressed by PBN and its derivatives. These results
      suggest that the change of c-jun expression is an excellent molecular marker for
      apoptosis mediated by intracellular oxidative stress induced by heat shock.

PMID- 15843895
TI  - Phosphorylation of Bad is not essential for PKB-mediated survival signaling in
      hemopoietic cells.
AB  - This study was designed to investigate Bad phosphorylation at several of its key
      regulatory Ser residues in cytokine-dependent hemopoietic cells. These studies
      were initiated in light of numerous studies that have reported a key role for
      phosphorylated Bad in preventing apoptosis. One key question is whether the
      survival signaling effect of the PI 3-kinase pathway is mediated by PKB
      phosphorylation of Bad. We confirm previous reports that if Bad is overexpressed
      or if active PKB is overexpressed, then the increased phosphorylation of Bad at
      Ser136 is apparent. However, we were unable to detect phosphorylation of
      endogenous Bad at Ser136 in the MC/9 mast cell line or in murine bone marrow
      derived macrophages. On the other hand, phosphorylation of Bad at Ser112 and
      Ser155 was observed in response to IL-3 or GM-CSF, which activate the MEK/erk
      pathway, but not with IL-4, which activates the PI 3-kinase, but not the MEK/erk
      pathway, and also promotes cell survival. In contrast to previous reports, we
      found that ceramide had no effect on the phosphorylation status of Bad. In
      summary, our results suggest that Bad phosphorylation at any of the three major
      sites is not a required event for cytokine-dependent cell survival, and in
      particular, the activation of PI 3-kinase/PKB pathway can be dissociated from
      phosphorylation of Bad at Ser136.

PMID- 15843896
TI  - Fenofibrate induces apoptotic injury in cultured human hepatocytes by inhibiting
      phosphorylation of Akt.
AB  - Fibric acid derivatives have a potent and effective lipid-lowering action,
      however, the use of these compounds is sometimes limited due to the occurrence of
      hepatic injury. In the present study, we characterized cell injury induced by
      fenofibrate in cultured human hepatocytes. Fenofibrate caused a loss of cell
      viability and nuclear damage as assessed by terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labeling or by DNA electrophoresis, in which caspase
      activation is involved. The cell injury was accompanied by the shrinkage and the
      translocation of phosphatidyl serine from inner membrane to the outer membrane as
      determined by annexin V stain. The mRNA expression for bcl-2 was reduced by
      fenofibrate. An immunofluorescent stain with antiserum raised against
      phosphorylated Akt revealed that fenofibrate inhibited insulin-stimulated
      phosphorylation of Akt. Like fenofibrate, several compounds that inhibit the
      phosphorylation of Akt, including wortmannin, SH-6 and a high concentration (100
      microM) of SB203580, reduced the viability of cultured human hepatocytes. Both
      nuclear damage and cell injury induced by fenofibrate were reversed by insulin in
      a concentration-dependent manner. In contrast, bezafibrate or 8(S)
      hydroxyeicosatetraenoic acid had no hepatotoxic action. These findings suggest
      that fenofibrate causes caspase-dependent apoptosis in human hepatocytes by
      inhibiting phosphorylation of Akt, in which PPARalpha is not involved.

PMID- 15843897
TI  - alpha-Lipoic acid induces apoptosis in human colon cancer cells by increasing
      mitochondrial respiration with a concomitant O2-*-generation.
AB  - The antioxidant alpha-lipoic acid (ALA) has been shown to affect a variety of
      biological processes associated with oxidative stress including cancer. We
      determined in HT-29 human colon cancer cells whether ALA is able to affect
      apoptosis, as an important parameter disregulated in tumour development. Exposure
      of cells to ALA or its reduced form dihydrolipoic acid (DHLA) for 24 h dose
      dependently increased caspase-3-like activity and was associated with DNA
      fragmentation. DHLA but not ALA was able to scavenge cytosolic O2-* in HT-29
      cells whereas both compounds increased O2-*-generation inside mitochondria.
      Increased mitochondrial O2-*-production was preceded by an increased influx of
      lactate or pyruvate into mitochondria and resulted in the down-regulation of the
      anti-apoptotic protein bcl-X(L). Mitochondrial O2-*-generation and apoptosis
      induced by ALA and DHLA could be prevented by the O2-*-scavenger benzoquinone.
      Moreover, when the lactate/pyruvate transporter was inhibited by 5-nitro-2-(3
      phenylpropylamino) benzoate, ALA- and DHLA-induced mitochondrial ROS-production
      and apoptosis were blocked. In contrast to HT-29 cells, no apoptosis was observed
      in non-transformed human colonocytes in response to ALA or DHLA addition. In
      conclusion, our study provides evidence that ALA and DHLA can effectively induce
      apoptosis in human colon cancer cells by a prooxidant mechanism that is initiated
      by an increased uptake of oxidizable substrates into mitochondria.

PMID- 15843898
TI  - Zinc pyrithione induces apoptosis and increases expression of Bim.
AB  - We demonstrate herein that zinc pyrithione can induce apoptosis at nanomolar
      concentrations. Zinc pyrithione was a potent inducer of cell death causing
      greater than 40-60% apoptosis among murine thymocytes, murine splenic lymphocytes
      and human Ramos B and human Jurkat T cells. Conversely, the addition of a zinc
      chelator protected thymocytes against zinc pyrithione induced apoptosis
      indicating these responses were specific for zinc. Zinc-induced apoptosis was
      dependent on transcription and translation which suggested possible regulation by
      a proapoptotic protein. Indeed, zinc induced a 1.9 and 3.4 fold increase
      respectively in expression of the BimEL and BimL isoforms and also stimulated
      production of the most potent isoform, BimS. This increase in Bim isoform
      expression was dependent on transcription being blocked by treatment with
      actinomycin D. Overexpression of Bcl-2 or Bcl-xL provided substantial protection
      of Ramos B and Jurkat T cells against zinc-induced apoptosis. Zinc also activated
      the caspase cascade demonstrated by cleavage of caspase 9. Addition of specific
      inhibitors for caspase 9 and caspase 3 also blocked zinc-induced apoptosis. The
      data herein adds to the growing evidence that free or unbound zinc could be
      harmful to cells of the immune system.

PMID- 15843900
TI  - Apoptosis and cell removal in the cryptorchid rat testis.
AB  - In order to determine that apoptosis is responsible for large-scale germ cell
      elimination, we analyzed cells from cryptorchid testes both in histological
      sections and among those isolated in vitro. Apoptotic testicular cells during 3
      to 7 days were only 8 to 30%, reaching a maximum of 80% by the end of 15 days of
      cryptorchidism. A similar trend was also observed with the number of dead cells.
      The process of large-scale germ cell removal in the initial stages was
      facilitated by the formation of multinucleated giant cells, which stained
      negative for apoptosis. Increase in oxidative stress and decrease in
      intratesticular testosterone was also observed. The above findings indicate that
      large-scale germ cell removal, at least during initial stages of cryptorchidism
      is not solely as a result of apoptosis. Declined intra testicular testosterone,
      elevated temperature and high oxidative stress following cryptorchidism probably
      affect cell viability and trigger a fast pace cell removal through giant cell
      formation.

PMID- 15843899
TI  - Iron deprivation induces apoptosis via mitochondrial changes related to Bax
      translocation.
AB  - In order to elucidate the mechanisms involved in apoptosis induction by iron
      deprivation, we compared cells sensitive (38C13) and resistant (EL4) to apoptosis
      induced by iron deprivation. Iron deprivation was achieved by incubation in a
      defined iron-free medium. We detected the activation of caspase-3 as well as the
      activation of caspase-9 in sensitive cells but not in resistant cells under iron
      deprivation. Iron deprivation led to the release of cytochrome c from
      mitochondria into the cytosol only in sensitive cells but it did not affect the
      cytosolic localization of Apaf-1 in both sensitive and resistant cells. The
      mitochondrial membrane potential (Deltapsi(m)) was dissipated within 24 h in
      sensitive cells due to iron deprivation. The antiapoptotic Bcl-2 protein was
      found to be associated with mitochondria in both sensitive and resistant cells
      and the association did not change under iron deprivation. On the other hand,
      under iron deprivation we detected translocation of the proapoptotic Bax protein
      from the cytosol to mitochondria in sensitive cells but not in resistant cells.
      Taken together, we suggest that iron deprivation induces apoptosis via
      mitochondrial changes concerning proapoptotic Bax translocation to mitochondria,
      collapse of the mitochondrial membrane potential, release of cytochrome c from
      mitochondria, and activation of caspase-9 and caspase-3.

PMID- 15843901
TI  - ER stress-induced caspase-12 activation is inhibited by PKC in neuronal cells.
AB  - Caspase-12 is activated when the cells are exposed to excess levels of various
      stimuli, which cause endoplasmic reticulum (ER) stress. Protein kinase C (PKC)
      plays an important role in many signaling pathways in cells, and the activation
      of PKC has multiple actions in the signaling function of the ER. This study
      examined whether or not phorbol 12, 13-dibutyrate (PDBu)-induced PKC activation
      modulates caspase-12 cleavage and it's processing, using a wild type caspase-12
      overexpressing neuronal cell line, known as Cas-12 cells. The thapsigargin
      treatment induced caspase-12 fragmentation in the Cas-12 cells. This was
      inhibited by PKC, which had previously been stimulated by PDBu. The PDBu
      treatment attenuated the ER stress-induced translocation of caspase-12 from the
      ER to the cytoplasm. The caspase-3 specific inhibitor blocked caspase-12
      fragmentation, and purified caspase-12 was cleaved by the active caspase-3 in
      vitro, suggesting that caspase-12 might be a substrate for caspase-3. In
      addition, the PDBu treatment influenced the decrease of active caspase-3
      fragment. These results suggest that an ER stress induces the activation of
      caspase-12 via caspase-3, and that PKC regulates both caspase-12 and caspase-3
      activations in Cas-12 cells.

PMID- 15843902
TI  - Structural and functional preservation of specific sequences of DNA and mRNA in
      apoptotic bodies from ES cells.
AB  - Retinoic acid-induced apoptosis of embryonic stem (ES) cells is an experimental
      system which resembles the physiological programmed cell death that occurs during
      differentiation in embryonic development. Our aim was to analyze the involvement
      of epigenetic modifications such as DNA methylation and chromatin structure in
      the apoptotic process and to investigate the metabolic activity of apoptotic
      bodies. We found a relationship between DNA methylation and apoptosis, shown by a
      dose-dependent induction of apoptosis after treatment with the inhibitor of DNA
      methylation 5-aza-2'-deoxycytidine. Interestingly, we found a slight
      demethylation of specific sequences of the U2afl-rs1 imprinted gene in those RA
      treated cells which were specifically undergoing apoptosis. In addition,
      apoptotic bodies exhibited an unexpected open chromatin conformation accessible
      to the endonuclease DNase-I. Furthermore, we observed a structural and functional
      preservation of specific DNA sequences and mRNA. These results suggest that
      biological activities, such as transcription or protein synthesis, could be
      maintained even towards the end of the apoptotic process.

PMID- 15843903
TI  - A novel time resolved fluorometric assay of anoikis using Europium-labelled
      Annexin V in cultured adherent cells.
AB  - BACKGROUND: Adherent cells undergo apoptosis when detached from their home
      ground, a process called anoikis (homelessness). METHODS: We developed a new and
      sensitive method to analyse apoptosis and anoikis of adherent cell types using a
      time resolved fluorometric assay with Europium-labelled Annexin V. Anoikis was
      induced with tumor necrosis factor-alpha/cycloheximide and three cell fractions
      of the cell cultures were prepared and analysed. Fraction 1 consisted of adherent
      cells, analysed while growing on their support (without detachment by
      trypsinisation). Fraction 2 contained detached cells due to anoikis (floating
      cells) and fraction 3 contained apoptotic bodies. Both fractions 2 and 3 were
      present in the culture medium and were isolated by differential centrifugation.
      RESULTS: TNF-alpha treatment of three different types of adherent cell cultures
      induced a significant increase of the amount of floating cells (anoikis) and
      apoptotic bodies compared to control cell cultures. Also in the adherent cell
      fractions a small amount of apoptosis was observed. CONCLUSIONS: The novel time
      resolved assay provides the ability to analyse the cell death cascade in adherent
      cell cultures of the same sample at the same time in a sensitive and reproducible
      way.

PMID- 15843904
TI  - Recruitment of beta-2-glycoprotein 1 to cell surfaces in extrinsic and intrinsic
      apoptosis.
AB  - Apoptotic cells and phagocytes have developed a diverse array of distinct ligand
      receptor systems that drive the recognition and uptake of dying cells. Phagocytes
      recognize apoptotic cells either directly, by binding to specific ligands at
      their cell surface, or indirectly, by binding to bridging proteins that bind
      these ligands. Previous observations showed that the plasma bridging protein
      beta2GP1, binds PS containing vesicles, and enhances their binding and engulfment
      by phagocytes in vitro. In this study we show that apoptotic cells injected
      intravenously and intraperitonealy into syngeneic mice recruited the PS binding
      protein, beta2GP1. Examination of peritoneal exudates and spleen thin sections
      showed that only the injected apoptotic cells picked up endogenous beta2GP1.
      Recovery of cells from the peritoneum showed that apoptotic cells bearing
      beta2GP1 were clustered around host peritoneal phagocytes. In addition, tissue
      sections from mice injected with Fas antibody showed colocalization of beta2GP1
      with TUNEL-positive apoptotic cells. These results provide evidence that
      endogenous beta2GP1 binds apoptotic cells in vivo, suggesting that the protein
      plays an important physiologic role in the recognition of dying cells.

PMID- 15843905
TI  - Stochastic modelling of apoptosis kinetics.
AB  - Robust quantitative estimation of average whole cell mitochondrial dysfunction is
      a useful tool for assessing sensitivity to apoptotic stimuli induced either by
      novel agents, or following manipulation of apoptotic threshold by pharmacological
      or functional genomics approaches. We have mathematically modelled the kinetics
      of whole cell mitochondrial membrane potential depolarisation within a population
      of cells as a Bernouli transition. An exponential distribution enables the median
      latency preceding mitochondrial membrane potential dissipation to be derived. The
      kinetic model can be fitted to in vitro single cell resolution data derived from
      kinetic flow cytometric studies by non-linear regression. We propose that kinetic
      determination of cumulative frequency distributions provides a useful approach
      for estimating apoptosis sensitivity across cell populations over short time
      frames.

PMID- 15843906
TI  - No prognostic impact of survivin expression in glioblastoma.
AB  - Survivin is a member of a novel protein family of inhibitors of apoptosis, and
      also plays a role as a potent regulator of mitosis. In semiquantitative Western
      blot analysis of glioblastomas, survivin expression was shown to be a
      prognostically significant factor. In the present study we investigated the
      immunohistochemical expression of survivin and its prognostic impact in a large
      glioblastoma series comprising 104 consecutive adult patients undergoing a first
      operation for glioblastoma. We analyzed survivin, Ki-67, and topoisomerase-II
      alpha expression in paraffin-embedded tissue, and correlated patient age,
      Karnofsky performance score, vascular pattern and survivin-, Ki-67-,
      topoisomerase-II-alpha-, and apoptotic indices with patient outcome using
      univariate and multivariate survival analysis. Survivin was expressed in all
      glioblastoma samples, and was prominent in a fraction of nuclei of tumor cells
      and vascular cells. Further, survivin labeled spindle- and chromosomal material
      of mitotic figures. Faint cytoplasmic expression was also seen. The survivin
      index showed significant correlation with Ki-67 and Topo-II-alpha indices. On
      average, 58.85% of Ki-67 and 91.08% of survivin-expressing nuclei co-expressed Ki
      67 and survivin. The survivin index did not correlate significantly with overall
      survival, whereas patient age, Karnofsky performance score, vascular pattern, and
      Ki-67 and topoisomerase-II-alpha indices were associated with patient outcome. In
      summary, in glioblastoma, survivin is expressed predominantly in proliferating
      tumor cell nuclei. In contrast to Ki-67 and topoisomerase-II-alpha, survivin
      expression does not influence patient outcome. So, in contrast to Ki-67, survivin
      does not seem to be useful as prognostic factor in the clinical setting.

PMID- 15843907
TI  - Involvement of mitochondria in myasthenia gravis complicated with dermatomyositis
      and rheumatoid arthritis: a case report.
AB  - We report a 57-year-old male with myasthenia gravis complicated with
      dermatomyositis and rheumatoid arthritis without evidence of thymoma. He showed
      prominent muscle wasting and weakness in the four extremities and trunk in
      addition to swallowing disturbance. He showed intolerance to exercise on a
      bicycle ergometer, and muscle biopsy specimens demonstrated ragged-red fibers. An
      anti-acetylcholine receptor (AChR) antibody was detected in his serum but no anti
      mitochondrial M2 component antibody was found. In contrast, results of
      immunohistochemical study indicated that his serum sample reacted to muscle
      mitochondria as well as AChR. These results indicate the presence of an
      unidentified anti-mitochondrial antibody that may be involved in the development
      of mitochondrial dysfunction in skeletal muscle of the present patient.

PMID- 15843908
TI  - [Vasopressin].

PMID- 15843909
TI  - [Indication for removal of tibial nails].
AB  - BACKGROUND: Tibial nail removal has been suggested as a routine procedure for
      both symptomatic and asymptomatic patients. The aim of this study was to define
      guidelines for the removal of tibial nails. PATIENTS AND METHODS: A retrospective
      study on the isolated removal of 69 tibial nails after fracture consolidation was
      done. A review of the patient charts and radiographs was performed. Forty-four
      patients (64%) were available for the follow-up interview. RESULTS:
      Preoperatively, 26 patients (59%) had local complaints. Of these 26 patients, 73%
      reported an improvement, and 8% reported an aggravation of their local
      complaints. Of the 18 patients who were asymptomatic before surgery, 17% reported
      long-term complaints at follow-up. CONCLUSION: We conclude that routine removal
      of tibial nails should be discussed critically in asymptomatic patients.

PMID- 15843910
TI  - [New observations on gut trauma].
AB  - Abdominal trauma from blunt objects remains a challenge in clinical practice. The
      primary aims are quick recognition and reversal of life-threatening situations,
      rational use of the available diagnostic methods, and avoidance of unnecessary
      laparotomy. The majority of these injuries can now be treated conservatively,
      whereby interventional methods such as drainage inserts and embolisation are
      becoming increasingly favoured. Observation of the treatment course by an
      experienced surgeon is a must. In patients with complicated injuries, special
      attention must be paid to so-called missed injuries: traumata that may be
      overlooked such as small intestine and diaphragm ruptures. Aside from retaining
      organs and their function, the most important concern is damage control (for
      complex injuries) and laparotomy in the abdominal compartment, with the
      application of temporary laparotomy as needed. These methods are aimed at
      reducing mortality pre- and post-admittance. However, we still lack valid
      prognostic parameters to allow realistic estimation of survival following severe,
      blunt abdominal trauma.

PMID- 15843911
TI  - [Multidetector computed tomography (MDCT) of the kidneys].
AB  - Multidetector computed tomography (MDCT) possesses distinct advantages for
      examination of the kidneys. It carries the potential of becoming the gold
      standard of diagnostic work-up and surgical planning for most renal diseases and
      replacing conventional methods such as i.v. urography and angiography. The most
      outstanding improvements, in comparison to single slice spiral CT, are the
      speedier image acquisition and enhanced z-axis resolution, which aids
      particularly in visualization of the urinary tract as it aligns along the axis of
      the body. Respiratory artifacts are few or nonexistent even in patients who
      cannot hold their breath. This overview presents a strategy for prudent
      management of MDCT examinations and describes examination of the most important
      and frequent renal diseases using MDCT.

PMID- 15843912
TI  - [Palpable lesion retromamillary and bloody secretion from the right breast].

PMID- 15843913
TI  - CAPS markers improved by cluster-specific amplification for identification of
      octoploid strawberry (Fragaria x ananassa Duch.) cultivars, and their disomic
      inheritance.
AB  - Cleavage amplified polymorphic sequence (CAPS) markers of strawberry (Fragaria x
      ananassa Duch.) can be useful for identifying mislabeled or patent-infringing
      cultivars in the marketplace. However, CAPS markers in octoploid strawberry tend
      to give unclear bands because multiple homologous sites are simultaneously
      amplified by the non-selective PCR. To overcome this problem, we used "cluster
      specific amplification" based on the nucleotide sequences of PCR products and
      were able to improve the band clarity of 18 CAPS markers. By analyzing the marker
      segregation ratio, we demonstrated that 13 clarified markers were derived from
      single diploid loci that were transmitted to progeny in a manner consistent with
      Mendelian inheritance. We discuss the genomic structure of octoploid strawberry
      from the viewpoint of cluster and segregation analysis and suggest that it
      comprises independent genomes. We tested the utility of all of the markers we
      developed for cultivar identification and confirmed their ability to distinguish
      among 64 strawberry cultivars.

PMID- 15843914
TI  - Effect of pramlintide on satiety and food intake in obese subjects and subjects
      with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Long-term trials in insulin-treated subjects with type 2
      diabetes have shown that adjunctive treatment with the amylin analogue
      pramlintide reduces HbA(1)c levels and elicits weight loss. While amylin reduces
      food intake in rodents, pramlintide's effect on satiety and food intake in humans
      has not yet been assessed. METHODS: In this randomised, double-blind, placebo
      controlled crossover study, 11 insulin-treated men with type 2 diabetes (age 60+/
      9 years, BMI 28.9+/-4.8 kg/m(2)) and 15 non-diabetic obese men (age 41+/-21
      years, BMI 34.4+/-4.5 kg/m(2)) underwent two standardised meal tests. After
      fasting overnight, subjects received single subcutaneous injections of either
      pramlintide (120 microg) or placebo, followed by a preload meal. After 1 h,
      subjects ate an ad libitum buffet meal. Energy intake and meal duration were
      measured, as were hunger ratings (using visual analogue scales), and plasma
      cholecystokinin, glucagon-like peptide-1 and peptide YY concentrations over time.
      RESULTS: Compared with placebo, pramlintide reduced energy intake in both the
      type 2 diabetes (Delta-202+/-64 kcal, -23+/-8%, p<0.01) and obese (Delta-170+/-68
      kcal, -16+/-6%, p<0.02) groups, without affecting meal duration. Hunger and
      hormonal analyte profiles provided evidence that pramlintide may exert a primary
      satiogenic effect, independently of other anorexigenic gut peptides.
      CONCLUSIONS/INTERPRETATION: The results indicate that enhanced satiety and
      reduced food intake may explain the weight loss observed in long-term pramlintide
      trials.

PMID- 15843915
TI  - Increasing the participation of children in clinical research.

PMID- 15843916
TI  - Is disturbance of consciousness an important feature of ICU delirium?

PMID- 15843918
TI  - Apoptosis of Jurkat cells induced by serum of patients with acute severe brain
      injury.
AB  - OBJECTIVE: To investigate the capacity of serum samples draining from the
      neuronal lesions to induce apoptosis of the lymphoid Jurkat cells in vitro and to
      analyze whether this effect is related to patient outcome. DESIGN AND SETTING:
      Prospective clinical investigation in a 21-bed intensive care unit (ICU) in a
      university hospital. PATIENTS: Forty-two patients who had suffered from acute
      brain injury (traumatic brain injury or spontaneous intracranial hemorrhage)
      requiring intensive care. INTERVENTIONS: Blood samples were obtained
      simultaneously from jugular bulb vein (regional) and from central venous catheter
      (systemic) on admission to the ICU and after 24, 48, and 72 h. Jurkat cells were
      incubated in the presence of 10% of heat-inactivated patients sera. The
      percentages of apoptotic cultured cells was measured by staining with annexin V
      and propidium iodide. MEASUREMENTS AND RESULTS: Regional serum draining from the
      lesions induced higher percentages of early and late apoptotic cells than
      systemic serum. The apoptotic effect was clearer with the sera from the patients
      who developed brain death. The apoptotic effect maintained a relationship with
      the mortality and the functional outcome at 6 months after the injury.
      CONCLUSIONS: Despite being performed on lymphoid cells because of the easier
      technical handling, our data help to elucidate the role of apoptosis for brain
      damage in acute brain injury. This and other undergoing studies on neuronal cells
      will enhance the understanding and management of apoptotic cell death in patients
      with acute brain injury admitted to the ICU.

PMID- 15843919
TI  - Function and pharmacology of TRPM cation channels.
AB  - The physiological function and cellular role of some members of the TRPM family
      are poorly understood and still mysterious. Melastatin, the founding member of
      the TRPM group, is the most prominent example of the mysteries involved in
      understanding TRP channel function. Melastatin or TRPM1 was first cloned in 1998
      and since then it has been suggested that it functions as a tumor suppressor
      protein in melanocytes. On the other hand, TRPM8 and TRPA1 have been described as
      cold receptors, TRPM4 and TRPM5 as calcium-activated nonselective cation
      channels, TRPM6 and TRPM7 as magnesium-permeable and magnesium-modulated cation
      channels, TRPM2 as an ADP-ribose-activated channel of macrophages, and TRPM3 as a
      hypo-osmolarity- and sphingosine-activated channel. There are many unsolved
      questions and many studies have to be performed to understand the overall
      function of the TRPM family. In addition to electrophysiological recordings and
      biochemical characterization, the use of compounds modulating TRPM channel
      function has often been helpful to study TRPM channels in a cellular context.
      Therefore, the review will summarize the known functions, activation mechanisms,
      and pharmacological modulations of the TRPM channels.

PMID- 15843920
TI  - Plasma time-of-flight mass spectrometry as a detector for short transient signals
      in elemental analysis.

PMID- 15843925
TI  - Periodontoid pseudotumor: CT and MRI imaging.
AB  - Periodontoid pseudotumor (PP) can be a severe and disabling disease. This disease
      process typically presents in elderly patients with a longstanding history of
      myelopathy. We reviewed four cases of PP in order to summarize the clinical and
      imaging features.

PMID- 15843926
TI  - Perineural extension of facial melanoma.
AB  - A 64-year-old man presented with a pigmented cutaneous lesion on the right side
      of his face along with right facial numbness. Histological examination revealed
      malignant melanoma. Magnetic resonance imaging (MRI) revealed perineural
      extension along the entire course of the maxillary division of the right
      trigeminal nerve. This is a rare but important manifestation of the spread of
      head and neck malignancy.

PMID- 15843927
TI  - Distribution of EPS and cell surface hydrophobicity in aerobic granules.
AB  - This study described the distribution of extracellular polysaccharides (EPS) and
      hydrophobicity in aerobic granule as well as the essential role of EPS in
      maintaining the stable structure of aerobic granules. Aerobic granules showed a
      heterogeneous structure, which had an outer shell with high biomass density and
      an inner core having a relatively low biomass density. Results showed that the
      outer shell of aerobic granule was composed of poorly soluble and noneasily
      biodegradable EPS, whereas its core part was filled with readily soluble and
      biodegradable EPS. It was further found that the shell of aerobic granule
      exhibited a higher hydrophobicity than the core of granule. The insoluble EPS
      present in the granule shell would play a protective role with respect to the
      structure stability and integrity of aerobic granules.

PMID- 15843928
TI  - Production of extracellular polymeric substances from Rhodopseudomonas acidophila
      in the presence of toxic substances.
AB  - A hydrogen-producing photosynthetic bacteria strain, Rhodopseudomonas acidophila,
      was used to investigate the production of extracellular polymeric substances
      (EPS) in the presence of toxic substances and the effect of toxicants on
      bacterial surface characteristics. Addition of the toxic substances including
      Cu(II), Cr(VI), Cd(II) and 2,4-dichlorophenol (2,4-DCP) stimulated the production
      of EPS but reduced the cell dry weight. At concentrations of 30 mg l(-1) Cu(II),
      40 mg l(-1) Cr(VI), 5 mg l(-1) Cd(II) and 100 mg l(-1) 2,4-DCP, the EPS content
      increased by 5.5, 2.5, 4.0 and 1.4 times, respectively, than the control. These
      toxic substances also greatly influenced the proteins/carbohydrates ratio of EPS.
      The ratios in the presence of toxic substances were always higher than that of
      control. Furthermore, under toxic conditions, the increase in the protein content
      far exceeded than that of others in EPS, suggesting that extracellular proteins
      could protect cells against toxic substances. The toxic substances significantly
      changed the surface characteristics and flocculation ability of R. acidophila,
      such as surface energy, relative hydrophobicity and free energy of adhesion.

PMID- 15843929
TI  - Transient accumulation of gamma-butyrolactone during degradation of bis(4-chloro
      n-butyl) ether by diethylether-grown Rhodococcus sp. strain DTB.
AB  - Rhodococcus sp. strain DTB (DSM 44534) grows aerobically on diethylether as sole
      source of carbon and energy. Dense cell suspension experiments showed that the
      induced ether-cleaving enzyme system attacks a broad range of ethers like
      tetrahydrofuran, phenetole and chlorinated alkylethers including Calpha
      substituted alkylethers. Identification of metabolites revealed that degradation
      of the ethers started by an initial attack of the ether bond. Diethylether-grown
      cells degraded bis(4-chloro-n-butyl) ether via an initial ether scission followed
      by the transient accumulation of gamma-butyrolactone as intermediate at nearly
      stoichiometric concentrations.

PMID- 15843930
TI  - Multiple large segment deletion method for Corynebacterium glutamicum.
AB  - A precise and scarless genome excision method, employing the Cre/loxP system in
      concert with double-strand break (DSB)-stimulated intramolecular recombination
      was developed. The DSBs were mediated by the restriction endonuclease, I-SceI. It
      permitted multiple deletions of independent 14-, 43-, and 10-kb-long genomic
      regions on the Corynebacterium glutamicum genome. Accuracy of deletion was
      confirmed by the loss of marker genes, PCR, and sequencing of new genome joints.
      Eleven, 58, and 4 genes were predicted on the 14-, 43-, and 10-kb deleted
      regions, respectively. Although the resultant mutant lost a total of 67 kb
      encoding 73 genes, it still exhibited normal growth under standard laboratory
      conditions. Such a large segment deletion method in which multiple, successive
      deletions are possible is useful for genome engineering.

PMID- 15843931
TI  - An unusual presenting feature of precursor T-cell acute lymphoblastic
      leukemia/lymphoma.

PMID- 15843932
TI  - The SIT4 gene, which encodes protein phosphatase 2A, is required for telomere
      function in Saccharomyces cerevisiae.
AB  - Life span and number of cell divisions in eukaryotes are limited. The
      accumulation of stress-associated damage due to ageing may cause irreversible
      cell cycle arrest, so-called "cellular senescence". Although many genes have been
      implicated in determining life span, regulatory systems that counteract age
      related stress have not yet been clarified. We examined senescence during a
      stress of Saccharomyces cerevisiae strains carrying disruptions in protein
      phosphatase (PPase)-encoding genes in order to identify the system counteracting
      senescence. Among these strains, short telomeres were found in the sit4
      disruptant that lacks one form of protein phosphatase 2A (PP2A). Silencing
      ability in the subtelomeric region was impaired and hyperphosphorylation of Sir3
      was also observed in this mutant. The sit4 mutant was found to have altered
      nucleoli and a life span as short as an sgs1 mutant. These observations suggest
      that the PP2A pathway regulates life span in yeast.

PMID- 15843933
TI  - Transformation of radish (Raphanus sativus L.) via sonication and vacuum
      infiltration of germinated seeds with Agrobacterium harboring a group 3 LEA gene
      from B. napus.
AB  - A protocol for producing transgenic radish (Raphanus sativus) was obtained by
      using both ultrasonic and vacuum infiltration assisted, Agrobacterium-mediated
      transformation. The Agrobacterium strain LBA4404 contained the binary vector
      pBI121-LEA (late embyogenesis abundant), which carried a Group 3 LEA gene, from
      Brassica napus. Among six combinations, Agrobacterium-mediated transformation
      assisted by a combination of 5-min sonication with 5-min vacuum infiltration
      resulted in the highest transformation frequency. The existence, integration and
      expression of transferred LEA gene in transgenic T(1) plants were confirmed by
      PCR, genomic Southern and Western blot analysis. Transgenic radish demonstrated
      better growth performance than non-transformed control plants under osmotic and
      salt stress conditions. Accumulation of Group 3 LEA protein in the vegetative
      tissue of transgenic radish conferred increased tolerance to water deficit and
      salt stress.

PMID- 15843934
TI  - Efficient callus induction and plant regeneration from anther of Chinese
      narcissus (Narcissus tazetta L. var. chinensis Roem).
AB  - Callus culture has, to date, been reported only in a few species of Narcissus. We
      used anthers of Chinese narcissus (Narcissus tazetta L. var. chinensis Roem) as
      explants for callus induction and plant regeneration. A high percentage of
      anthers at the early- to mid-uninucleate microspore stage were responsive on the
      basal MS medium supplemented with 0.5-1 mg l(-1) 2,4-dichlorophenoxyacetic acid
      and 0.5-2 mg l(-1) 6-benzyladenine under dark conditions. Calli were initiated
      from anther connective tissue or anther wall tissue, and no division of
      microspores occurred during callus formation, as determined by histological
      observation. Using 20 random amplified polymorphic DNA primers, we verified the
      genetic integrity of the anther-derived plants of Chinese narcissus with respect
      to the donor plants. These results suggest that anther culture in vitro can
      provide an efficient new micropropagation technique for Chinese narcissus as well
      as a new strategy for in vitro mass propagation of other daffodils.

PMID- 15843936
TI  - Rhabdomyosarcoma relapse in an unusual site.
AB  - Lower genitourinary tract rhabdomyosarcoma is the most common soft tissue sarcoma
      in children. Recurrence is common but usually occurs at the original site. A case
      of a young boy with recurrent rhabdomyosarcoma at an unusual site (glans penis)
      is presented.

PMID- 15843935
TI  - Assessment of cortical maturation with prenatal MRI: part II: abnormalities of
      cortical maturation.
AB  - The fetal cortical maturation is a long process with predefined steps.
      Abnormalities can occur at different stages of cortical maturation, resulting in
      various malformations. They can result from disturbance in cell proliferation,
      cell differentiation, cell migration and in organization of the cortex. Analysis
      of the different abnormalities of cortical maturation is given with illustrations
      of the principal malformations encountered in utero and accessible to MRI.

PMID- 15843937
TI  - Sclerosing therapy of internal hemorrhoids with a novel sclerosing agent.
      Comparison with ligation and excision.
AB  - BACKGROUND AND AIMS: Patients with prolapsing internal hemorrhoids were treated
      with a novel sclerosing agent (OC-108), and the results were compared with
      surgery of ligation and excision. PATIENTS AND METHODS: This study included 20
      years or older patients with prolapsing internal hemorrhoids who visited ten
      medical institutions in Japan from October 2000 to October 2002. Investigation on
      surgery was also performed. RESULTS: Comparing OC-108 and surgery in patients
      with third- and fourth-degree internal hemorrhoids according to the Goligher's
      classification, for which surgery has been generally indicated, at 28 days after
      treatment, the disappearance rate of prolapse was similar between OC-108 and
      surgery, 94% (75/80 patients) and 99% (84/85 patients), respectively. The 1-year
      recurrence rate was 16% (12/73 patients) in the OC-108 group, and this value was
      satisfactory because of its less invasive nature while it was more or less higher
      compared with 2% (2/81 patients) in the surgery group. The incidences of pain and
      bleeding were lower in the OC-108 group. CONCLUSIONS: OC-108 is a useful
      alternative treatment for hemorrhoids.

PMID- 15843938
TI  - Prospective, randomised study on antibiotic prophylaxis in colorectal surgery. Is
      it really necessary to use oral antibiotics?
AB  - BACKGROUND AND AIMS: The use of prophylactic antibiotics in addition to
      mechanical cleansing is the current standard of care prior to colonic surgery.
      The question of whether the antibiotics should be administered intravenously or
      orally, or by both routes, remains controversial. Our aim was to compare three
      methods of prophylactic antibiotic administration in elective colorectal surgery.
      METHODS: Three hundred consecutive elective colorectal resections were studied.
      All patients had preoperative mechanical colon cleansing with oral sodium
      phosphate and intravenous antibiotic prophylaxis with cefoxitin (one dose before
      skin incision and two postoperative doses). Patients were randomised to one of
      the following three groups: group A: three doses of oral antibiotic (neomycin and
      metronidazole) at the time of mechanical colon cleansing; group B: one dose of
      oral antibiotic; group C: no oral antibiotics. All patients were followed during
      their hospital stay and at 7, 14 and 30 days post-surgery. RESULTS: Vomiting
      occurred in 31%, 11% and 9% of the studied patients (groups A, B and C,
      respectively) (p<0.001). Nausea was present in 44%, 18% and 13% of patients
      (p<0.001). Abdominal pain was recorded in 13%, 10% and 4% of patients (p: 0.077).
      Wound infection was present in 7%, 8% and 6% and suture dehiscence occurred in
      2%, 2% and 3% of the patients in the three groups (no differences among them).
      Neither were differences found among the three groups in terms of urinary
      infections, pneumonia, postoperative ileus or intra-abdominal abscess.
      CONCLUSION: The addition of three doses of oral antibiotics to intravenous
      antibiotic prophylaxis is associated with lower patient tolerance in terms of
      increased nausea, vomiting and abdominal pain, and has shown no advantages in the
      prevention of postoperative septic complications. Therefore, we recommend that
      oral antibiotics should not be used prior to colorectal surgery.

PMID- 15843939
TI  - Sacral nerve stimulation for faecal incontinence following a rectosigmoid
      resection for colorectal cancer.
AB  - INTRODUCTION: Following recto-sigmoid resection some patients may become faecally
      incontinent and remain so despite conservative treatment. This multicentre
      prospective study assessed the use of sacral nerve stimulation (SNS) in this
      group. METHODS: All patients had more than or equal to 4 days of faecal
      incontinence for solid or liquid stools over a 21-day period following recto
      sigmoid resection for colorectal carcinoma. The operation had to have been deemed
      curative. They had to have failed pharmacological and biofeedback treatment.
      RESULTS: Three male patients met these criteria. One had had a colo-anal and two
      a colo-rectal anastomosis for rectal carcinoma. All patients had intact internal
      and external anal sphincters. Two patients had a successful temporary stimulation
      period and proceeded to permanent implantation. Pre-operative symptom duration
      was 1 year in the permanently implanted patients. They were followed up for 12
      months. SNS improved the number of faecally incontinent episodes in both
      patients. Ability to defer was improved in both patients from 0--5 min to 5--15
      min. The faecal incontinence-specific ASCRS quality of life assessment improved
      in all four subcategories. CONCLUSION: This study demonstrates that SNS may be
      effective in the treatment of patients with faecal incontinence following recto
      sigmoid resection if conservative treatment has failed.

PMID- 15843940
TI  - Prospective randomised clinical trial of single versus double purse-string
      stapled mucosectomy in the treatment of prolapsed haemorrhoids.
AB  - BACKGROUND AND AIMS: Despite the excellent results published on circular stapled
      mucosectomy (CSM), there is still some concern about the application of PPH-33 in
      the advanced haemorrhoidal disease, where a major prolapse may lead to
      insufficient resection and ensuing early recurrence. This study is aimed at
      comparing the outcomes after single purse-string CSM versus double purse-string
      CSM. PATIENTS AND METHODS: A prospective randomised clinical trial of single
      versus double purse-string CSM for grade III-IV symptomatic haemorrhoids was
      used. One hundred consecutive patients were randomised to single (group 1, N=50)
      versus double purse-string CSM (group 2, N=50). RESULTS: The mean age was 50.7
      years, with a predominance of males (63 vs. 37). Haemorrhoids were classified as
      grade III in 59% and grade IV in 41% of the patients. Mean follow-up was 26
      months. Demographic and clinical features showed no differences between the two
      groups. The size of the resected doughnut was greater in group 2 (4.95 vs. 3.55
      cm; p<0.05), as was the distance of the suture from the dentate line (3.56 vs.
      3.16 cm; p<0.05). Early postoperative pain was significantly less in group 2
      (linear analogue scale from 0 to 10), 2.08 vs. 3.56 (p<0.001). Postoperative
      haemorrhage was absent or minimal in 79% of patients. Three patients from group 1
      reported persistent pain that was resolved within the first few postoperative
      months. There were two recurrences in group 1. CONCLUSION: Double purse-string
      CSM resects a greater doughnut, increases the distance of the staple suture from
      the dentate line and reduces early postoperative pain in comparison to single
      purse-string CSM. Larger series are necessary to assert whether recurrence is
      lower.

PMID- 15843941
TI  - Surgical treatment the sacral fracture in childhood: case report and literature
      overview.
AB  - Fractures of the sacrum in children are rare. In the 17 cases described in the
      past 25 years, surgery was indicated only for treatment of the consequences of
      the primary injury. We present the case of a 10-year-old girl who sustained the
      following injuries as a result of a fall from a swing: posterior angulation of
      S2/3 with suspected injury of anterior ligamentous structures, fracture of the
      proximal part of the S4 body with a displacement by the bone width anteriorly and
      contraction of 5 mm, posterior angulation of S5/Co1 also with a suspected injury
      of anterior ligamentous structures. After an unsuccessful attempt at closed
      reduction, open reduction and fixation by two K-wires was indicated. The fracture
      healed in 8 weeks. Two years after the treatment, the patient is without
      complaints and limitations. The question is whether surgery was necessary for
      treatment of this fracture or whether spontaneous healing and subsequent
      remodelling of the sacral bone in such a young patient may be expected which
      would be also fully satisfactory. In our view, the described surgical treatment
      was appropriate and is definitely indicated for patients with a similar injury
      associated with a neural lesion.

PMID- 15843942
TI  - Traumatic musculocutaneous neuropathy: a case report.
AB  - Isolated injury of the musculocutaneous nerve is a rare disorder. Reported cases
      are claimed to present with loss of biceps and brachialis power without a
      disturbing pain. The injury generally occurs after strenuous exercise and could
      be demonstrated by electrophysiological examination. We report a case of
      musculocutaneous nerve injury which occurred after a vigorous push and which
      presented with unusual symptoms and findings. The patient complained of episodic
      severe pain attacks which started from the axilla and radiated over the
      musculocutaneous nerve distribution including the lateral antebrachial cutaneous
      nerve area. He did not respond to 3 months of conservative treatment including
      multiple corticosteroid injections and finally required surgical release.
      Surgical epineurotomy resulted in immediate relief. This is the first reported
      case of acute musculocutaneous nerve injury presenting with unusual symptoms and
      findings. The operative release procedure performed was also not required in any
      of the other reported cases. An excellent result was obtained with epineurotomy.

PMID- 15843943
TI  - Indirect spinal canal decompression of vertebral burst fracture in calf model.
AB  - INTRODUCTION: An experimental study of experimental burst fractures in bovine
      spinal specimens was conducted to analyze the effects of transpedicular short
      segment posterior fixation followed by reduction on indirect spinal canal
      decompression. MATERIALS AND METHODS: For this purpose, experimental burst
      fractures were created in 11 bovine specimens with a hydraulic materials-testing
      machine. The specimens were evaluated with plain radiographs and CT scans before
      reduction. Thereafter, they were instrumented with titanium transpedicular screws
      and rods (short-segment posterior fixation); and reduction was achieved which
      included distraction and kyphosis correction maneuvers. RESULTS: Each spinal
      specimen was evaluated with plain radiographs and CT scans after reduction by
      applying distraction and kyphosis correction maneuvers. Plain radiographic
      analysis showed that the kyphosis angle and segmental height values improved.
      Furthermore, CT scans revealed that the spinal canal diameter values improved
      compared with those before reduction. The differences between before and after
      reduction in kyphosis angle, segmental height, anterior body compression, and
      percentage of retropulsion were statistically significant. CONCLUSION: Short
      segment posterior fixation followed by indirect spinal canal decompression led to
      an improvement over spinal canal retropulsion in experimental burst fractures.
      Furthermore, the kyphosis angle and segmental height values improved following
      the reduction compared with those before reduction.

PMID- 15843944
TI  - Traumatic hemipelvectomy: case report and literature review.
AB  - Traumatic hemipelvectomy is a rare but devastating injury involving complete
      disruption of the hemipelvis from the pubic symphysis to the sacroiliac joints
      and often results in death. We present an interesting case of traumatic
      hemipelvectomy caused by a previously undescribed mechanism of injury in which
      judicious angiography and aggressive surgical treatment contributed to patient
      survival.

PMID- 15843945
TI  - Inter- and intraobserver assessment of periacetabular osteodensitometry after
      cemented and uncemented total hip arthroplasty using computed tomography.
AB  - INTRODUCTION: This study was initiated to evaluate the reproducibility of a novel
      method for measuring the periacetabular bone density after insertion of cemented
      and uncemented acetabular cups using CT in vivo. MATERIALS AND METHODS: CT scans
      were obtained from 20 patients after cemented polyethylene cup implantation (ZCA,
      Zimmer, USA) and 20 patients after uncemented titanium alloy cup fixation
      (Cerafit, Ceraver, France). A manual segmentation of cancellous and cortical
      pelvic bone ventral, dorsal and cranial to the cup was undertaken. Values are
      given in Hounsfield units. Inter- and intraobserver studies were conducted using
      a special analysis software tool. To define the reproducibility of the method,
      all measurements were evaluated according to Bland and Altman. RESULTS: For both
      cemented and uncemented acetabular cups, reproducibility of bone density
      measurement for cortical and cancellous bone cranial, ventral and dorsal to the
      cup was high. There was no significant difference between the intraobsever study
      (two repeated measurements) and the interobserver study (two investigators),
      indicating the reproducibility of the method independent of the investigator.
      CONCLUSION: In conclusion, the periacetabular bone density measurement as
      conducted in this CT study is a new reproducible method for in vivo evaluation of
      cortical and cancellous pelvic bone after cemented and uncemented acetabular cup
      implantation. In vivo CT measurements will allow a thorough assessment of
      periacetabular stress-shielding phenomena.

PMID- 15843946
TI  - The effect of intermittent pneumatic compression on the bone uptake of (99m)Tc
      labelled methylene diphosphonate in the lower limb.
AB  - INTRODUCTION: Venous compression of the lower limbs will obstruct outflow through
      the deep and superficial veins, yet inflow will continue, without continual
      swelling of the limb. It is hypothesised that venous channels in the long bones
      act as collateral channels to restore outflow, and therefore general blood flow
      through bone will increase. Such a hemodynamic change should affect the uptake of
      radiopharmaceuticals by the bone, though uptake changes in themselves would not
      definitely indicate flow changes. The purpose of this study, therefore, was to
      determine whether bone uptake in the lower limb is affected by intermittent
      venous compression, irrespective of the mechanism involved. MATERIALS AND
      METHODS: The effect of intermittent pneumatic compression of the thigh and calf
      on the uptake of (99m)Tc-methylene diphosphonate (MDP) was studied in 24
      patients. All were undergoing routine bone imaging for medical conditions that
      were not focused on their lower limbs, and received 1 h of the therapy at 60 mmHg
      on one limb only, after injection of the radiopharmaceutical. Three hours after
      injection the relative difference in uptake (net counts per pixel) between the
      two limbs was calculated. The standard imaging protocol was otherwise unchanged.
      RESULTS: The median differences in uptake in the intermittently compressed limb
      compared with the contralateral limb were +7.6% (interquartile range +3.9% to
      +16.0%, p<0.0005 [Wilcoxon]) for the anterior aspect of the femur; +11.7%
      (interquartile range +4.3% to +22.2%, p<0.0005) posterior, femur; +10.5%
      (interquartile range +6.5% to +13.8%, p<0.0005) anterior, tibia; +10.6%
      (interquartile range +5.5% to +17.6%, p<0.0005) posterior, tibia. CONCLUSION:
      Intermittent pneumatic compression clearly and significantly increased the uptake
      of (99m)Tc-MDP in long bones. These data are consistent with increases in blood
      flow through bone, though a direct mechanical influence on the bone cannot be
      excluded. This effect should be given consideration during routine therapeutic
      and thromboprophylactic use of intermittent compression, and if the mechanism of
      the uptake changes can be established, their possible clinical uses should be
      investigated.

PMID- 15843947
TI  - Radiation exposure to the hands of orthopaedic surgeons: are we underestimating
      the risk?
AB  - INTRODUCTION: Previous studies reported that the radiation exposure to the hands
      of orthopaedic surgeons was far below the acceptable limit. However, the risk
      could have been underestimated as some factors were overlooked, namely monitoring
      trainees during average workload, placing dosimeters over the most susceptible
      locations, measuring the cumulative dosage of radiation and considering the dose
      limit for non-classified workers. MATERIALS AND METHODS: We performed a
      prospective study in two centres to estimate the radiation dose to the hands of
      two consultant trauma surgeons and two trainees (one assisting and one operating)
      while performing 47 fluoroscopy-assisted procedures. We used validated
      thermoluminescent dosimeters (TLDs) rings and fingerstalls for monitoring the
      cumulative dosage. RESULTS: Trainees were at higher risk while performing
      intramedullary nailing and during assistance. Higher radiation doses were
      recorded from dominant index fingers and particularly fingertips. CONCLUSION: The
      risk of radiation exposure appears to be higher than previously reported.
      Fingertips are more susceptible to radiation exposure and should therefore be
      monitored in forthcoming studies.

PMID- 15843948
TI  - Fractures in the proximal humerus: functional outcome and evaluation of 70
      patients treated in hospital.
AB  - INTRODUCTION: Patients with proximal humeral fractures are mostly elderly. In
      addition to the proximal humeral fracture, they often have other injuries related
      to poor bone quality. The surgical treatment of proximal humeral fractures in
      elderly patients with comminuted fractures is associated with several problems
      and a high frequency of complications. The aims of this study were to evaluate
      patients with a proximal humeral fracture treated in a hospital, assess the
      outcome of the fracture treatment, and decide whether surgical treatment of
      displaced proximal humeral fractures is superior to conservative treatment or
      not. MATERIALS AND METHODS: Patients with fractures of the proximal part of the
      humerus treated in our hospital were followed during two different periods (14
      and 10 months). The study in the first time period was retrospective in design,
      while in the second period the patients were followed prospectively. Seventy
      patients, (71% women) with a mean age of 71 years, were included in the study. A
      functional test was performed within 12-14 months after the injury using a
      modified Rowe shoulder score. Surgical treatment was performed in 15 patients
      (21%). Neither the surgical approach nor the implants used for osteosynthesis
      were standardized. Fifty-five patients (79%) were treated conservatively with a
      modified Velpeau bandage or a sling. RESULTS: The fractures were classified
      according to AO into type A (27%), type B (58%) and type C (14%). Osteoporotic
      risk factors were present in many of the patients, mainly characterized by other
      skeletal injuries than the proximal humeral fracture (43%). In the group of
      complex, displaced, non-impacted fractures B2, B3, C2, C3 included (20
      fractures), the group treated conservatively had a mean Rowe score of 48/75 (64%
      of maximum score) and SD 16.8, while in the surgically treated group the mean
      score was 28/75 (38% of maximum score) and SD 8.1. The difference between the two
      treatments was significant, with a p-value of 0.01 in favour of the
      conservatively treated group. CONCLUSION: The number of patients in each of the
      fracture groups was low, but surgery did not benefit the patients with complex,
      displaced fractures in this study.

PMID- 15843949
TI  - Dysplasia epiphysealis hemimelica (Trevor's disease) of the acetabulum.
AB  - Unphysiological joint stress leads to problems and subsequently to joint
      destruction. We report a rare case of dysplasia epiphysialis hemimelica (DEH) of
      the triradiate cartilage of the acetabulum. In addition to clinical symptoms, we
      point out the specific therapy and outcome of the afflicted child.

PMID- 15843950
TI  - Rupture of the pregnant uterus: a 9-year review.
AB  - OBJECTIVE: To investigate the frequency of ruptured uterus, possible etiologic
      factors and fetomaternal outcomes. STUDY DESIGN: A retrospective chart view of
      all patients with ruptured uterus over a 9-year period from 1995 to 2003 was
      carried out. Relevant data relating to the clinical features, characteristics of
      labour, operative procedures, and fetomaternal outcomes were assessed. RESULTS:
      During the study period there were 17 cases of ruptured uterus among a total of
      117,095 deliveries, giving an incidence of 1 in 6,888 deliveries. Thirteen
      patients (76.5%) were multiparous and mean parity was 1.9. Uterine rupture
      occurred following vaginal delivery in ten patients. Caesarean delivery was
      performed in seven (41.2%) patients, of which five (29.4%) patients had a history
      of previous caesarean section. Abdominal hysterectomy was performed in 12
      patients (70.6%), of which 9 (75.0%) were total and 3 (25.0%) were subtotal. The
      other five patients (29.4%) had suture repairs. In seven patients (41.2%),
      uterine rupture was associated with oxytocin use. There were one maternal and
      three perinatal (17.6%) deaths. CONCLUSION: Sudden fetal heart abnormalities in
      labouring patients should be taken as a potential sign of danger. Early diagnosis
      and immediate preoperative resuscitation are of great importance in cases of
      ruptured uterus. The fetomaternal outcomes can be improved with the experience
      and skill of the surgical team.

PMID- 15843952
TI  - Non-reciprocal chromosomal bridge-induced translocation (BIT) by targeted DNA
      integration in yeast.
AB  - Several experimental in vivo systems exist that generate reciprocal
      translocations between engineered chromosomal loci of yeast or Drosophila, but
      not without previous genome modifications. Here we report the successful
      induction of chromosome translocations in unmodified yeast cells via targeted DNA
      integration of the KAN(R) selectable marker flanked by sequences homologous to
      two chromosomal loci randomly chosen on the genome. Using this bridge-induced
      translocation system, 2% of the integrants showed targeted translocations between
      chromosomes V-VIII and VIII-XV in two wild-type Saccharomyces cerevisiae strains.
      All the translocation events studied were found to be non-reciprocal and the fate
      of their chromosomal fragments that were not included in the translocated
      chromosome was followed. The recovery of discrete-sized fragments suggested
      multiple pathway repair of their free DNA ends. We propose that centromere-distal
      chromosome fragments may be processed by a break-induced replication mechanism
      ensuing in partial trisomy. The experimental feasibility of inducing chromosomal
      translocations between any two desired genetic loci in a eukaryotic model system
      will be instrumental in elucidating the molecular mechanism underlying genome
      rearrangements generated by DNA integration and the gross chromosomal
      rearrangements characteristic of many types of cancer.

PMID- 15843951
TI  - Telomere biology: integrating chromosomal end protection with DNA damage
      response.
AB  - Telomeres play the key protective role at chromosomes. Many studies indicate that
      loss of telomere function causes activation of DNA damage response. Here, we
      review evidence supporting interdependence between telomere maintenance and DNA
      damage response and present a model in which these two pathways are combined into
      a single mechanism for protecting chromosomal integrity. Proteins directly
      involved in telomere maintenance and DNA damage response include Ku, DNA-PKcs,
      RAD51D, PARP-2, WRN and RAD50/MRE11/NBS1 complex. Since most of these proteins
      participate in the repair of DNA double-strand breaks (DSBs), this was perceived
      by many authors as a paradox, given that telomeres function to conceal natural
      DNA ends from mechanisms that detect and repair DSBs. However, we argue here that
      the key function of one particular DSB protein, Ku, is to prevent or control
      access of telomerase, the enzyme that synthesises telomeric sequences, to both
      internal DSBs and natural chromosomal ends. This view is supported by
      observations that Ku has a high affinity for DNA ends; it acts as a negative
      regulator of telomerase and that telomerase itself can target internal DSBs. Ku
      then directs other DSB repair/telomere maintenance proteins to either repair DSBs
      at internal chromosomal sites or prevent uncontrolled elongation of telomeres by
      telomerase. This model eliminates the above paradox and provides a testable
      scenario in which the role of DSB repair proteins is to protect chromosomal
      integrity by balancing repair activities and telomere maintenance. In our model,
      a close association between telomeres and different DNA damage response factors
      is not an unexpected event, but rather a logical result of chromosomal integrity
      maintenance activities.

PMID- 15843953
TI  - Cross-sectional view of factors associated with back pain.
AB  - OBJECTIVE: To examine the factors associated with back pain within a working
      population. METHODS: A cross-sectional survey of employees using a self
      administered questionnaire and physical fitness tests. This study assessed 10,321
      participants (6,251 male and 4,070 female) of two nationwide companies throughout
      Switzerland between 1996 and 1998. The participation rate was 41%. RESULTS: Of
      the participants, 4,945 (48%) suffered mild back pain and 696 (7%) suffered
      severe back pain. Reported "stress" was associated with back pain of any
      intensity. Abdominal muscle strength was inversely associated with severe back
      pain, while physical activity was non-linearly associated with severe back pain.
      Smoking was directly associated with any intensity of back pain. The variables
      gender, obesity, strength of the abdominal musculature and frequency of physical
      activity were insignificant for back pain of any intensity in multivariate
      analyses. CONCLUSION: Our results confirm the association of back pain with
      physical and behavioural factors. The non-linear relationship between physical
      activity and back pain may need further examination. Performing any kind of sport
      three to four times a week appears optimal.

PMID- 15843954
TI  - Prevalence of musculoskeletal pain and associated factors in the Quebec working
      population.
AB  - BACKGROUND: While the determinants of musculoskeletal pain are numerous, few
      studies conducted among workers have taken into account, altogether, physical
      factors, psychosocial factors (personal and work-related) and individual
      characteristics. OBJECTIVES: To estimate the 1-year prevalence of musculoskeletal
      pain in the Quebec working population by gender and anatomical site, and to
      determine which factors are associated with these prevalence figures. METHODS:
      Data came from the 1998 Quebec Health Survey and included 9,496 individuals. One
      year period prevalences for neck pain, back pain and pain in the upper and lower
      extremities were calculated for men and women. Logistic regression analyses were
      conducted to estimate the associations between individual, physical and
      psychosocial work factors, on one hand, and musculoskeletal pain in the four body
      regions, on the other hand. RESULTS: For both genders back pain was the most
      frequent musculoskeletal symptom that had disturbed their activities during the
      past year. The largest difference between genders was observed for neck pain
      (women: 18%; men: 11%). Multivariate analyses indicated that physical and
      psychosocial work factors, as well as psychological variables, were associated
      with musculoskeletal pain in different body regions. Body mass index was
      associated only with pain in lower extremities for both genders. CONCLUSIONS: The
      results of this study suggest that interventions aimed at reducing
      musculoskeletal pain should take into account personal and work-related
      psychosocial variables, in addition to physical workload.

PMID- 15843955
TI  - Ill health and early retirement among school principals in Bavaria.
AB  - OBJECTIVES: School principals play an important role in maintaining the
      performance and health of teachers but often feel over-burdened themselves and
      suffer illnesses, which not only impairs their health-promoting function but also
      leads to limitations in their fitness for the occupation. The aim of our study
      was, therefore, using objective parameters and larger numbers of cases, to obtain
      a differentiated insight into the morbidity and the health-related early
      retirement of school principals. METHODS: In a prospective total assessment (the
      whole of Bavaria, a state in southern Germany) in the period from 1997 to 1999
      all medical examinations of school principals performed to decide the question of
      early retirement were evaluated. The analysis included, e.g., socio
      demographic/occupational factors, diagnoses, assessment of performance and
      rehabilitation. The data were sampled in a standardised, anonymous questionnaire,
      which provided the database. Evaluation was carried out by means of descriptive
      statistics. RESULTS: The median age of the 408 school principals included in the
      evaluation (heads and vice-heads, 30% of whom were women) was 58 years (minimum
      41 years, maximum 64 years). The most frequent workplaces were primary schools
      (63%). A total of 84% (n=342) of the headmasters was assessed to be unfit for
      work. The main reasons for early retirement were psychiatric/psychosomatic
      disorders (F-ICD 10) which made up 45% of the cases. The relative frequency was
      higher in women than in men. Depressive disorders and exhaustion syndromes
      (burnout) dominated among the psychiatric diagnoses (proportion 57%). The most
      frequent somatic illnesses were cardiovascular diseases (I-ICD10) in 19% of
      cases, then muscular/skeletal diseases (M-ICD10) in 10% and malignant tumours (C
      ICD 10) in 9% of cases. Cardiovascular diseases, in particular arterial
      hypertension and ischaemic heart disease, were found in headmasters significantly
      more frequently than in teachers without a headship function (P</=0.05). A total
      of 63% (n=257) of the school principals had participated in at least one medical
      rehabilitation before the proceedings for determining unfitness for work were
      instigated. The performance of 66% (n=226) of those judged unfit for work was
      assessed to be so severely impaired that no other employment could be expected of
      them. CONCLUSIONS: The morbidity spectrum of school principals prematurely unfit
      for work is characterised by stress-associated diseases. The health disorders
      objectified are of considerable relevance for policy and administration. Specific
      prevention and intervention must, therefore, also include this occupational
      group. Activity should not be limited to the prevention of behavioural problems
      but should also take into account important aspects for preventing adverse
      circumstances arising at the school workplace.

PMID- 15843956
TI  - Effect of skin temperature on the ion reabsorption capacity of sweat glands
      during exercise in humans.
AB  - The effect of skin temperature on the ion reabsorption capacity of sweat glands
      during exercise in humans is unknown. In this study, eight healthy subjects
      performed a 60-min cycling exercise at a constant intensity (60% VO(2max)) under
      moderate (25 degrees C) and cool (15 degrees C) ambient temperatures at a
      constant relative humidity of 40%. The sweating rate (SR), index of sweat ion
      concentration (ISIC) by using sweat conductivity, esophageal temperature (Tes),
      mean skin temperature, and heart rate (HR) were measured continuously under both
      ambient temperatures. The SR and ISIC were significantly lower at the cool
      ambient temperature versus the moderate temperature. There were no significant
      differences in the changes in HR and esophageal temperature between these ambient
      temperature conditions, while the mean skin temperature was significantly lower
      at the cool ambient temperature by almost 3 degrees C (P < 0.05). The slopes of
      the relationships between Tes and the SR and ISIC were significantly lower and
      the thresholds of these relationships were significantly higher at the cool
      ambient temperature (P < 0.05). The ion reabsorption capacity of the sweat glands
      was significantly lower (P < 0.05) in a cool environment (0.21 +/- 0.04 vs. 0.52
      +/- 0.06 mg/cm(2)/min at 15 and 25 degrees C, respectively) as evaluated using
      the relationships for SR and ISIC. The results suggest that the ion reabsorption
      capacity of the sweat glands is influenced by skin temperature during exercise in
      humans.

PMID- 15843957
TI  - High-intensity intermittent running training improves pulmonary function and
      alters exercise breathing pattern in children.
AB  - We investigated the effects of short duration running training on resting and
      exercise lung function in healthy prepubescent children. One trained group (TrG)
      (n = 9; three girls and six boys; age = 9.7 +/- 0.9 year) participated in 8 weeks
      of high-intensity intermittent running training and was compared to a control
      group (ContG) (n = 9; four girls and five boys; age = 10.3 +/- 0.7 year). Before
      and after the 8-week period, the children performed pulmonary function tests and
      an incremental exercise test on a cycle ergometer. After the 8-week period, no
      change was found in pulmonary function in ContG. Conversely, an increase in
      forced vital capacity (FVC) (+7 +/- 4% ; P = 0.026), forced expiratory volume in
      one second (+11 +/- 6% ; P = 0.025), peak expiratory flows (+17 +/- 4% ; P =
      0.005), maximal expiratory flows at 50% (+16 +/- 10% ; P = 0.019) and 75% (+15 +/
      8% ; P = 0.006) of FVC were reported in TrG. At peak exercise, TrG displayed
      higher values of peak oxygen consumption (+15 +/- 4% ; P < 0.001), minute
      ventilation (+16 +/- 5% ; P = 0.033) and tidal volume (+15 +/- 5% ; P = 0.019)
      after training. At sub-maximal exercise, ventilatory response to exercise
      DeltaV(E)/DeltaV(CO(2)) was lower (P = 0.017) in TrG after training, associated
      with reduced end-tidal partial oxygen pressure (P < 0.05) and higher end-tidal
      partial carbon dioxide pressure (P = 0.026). Lower deadspace volume relative to
      tidal volume was found at each stage of exercise in TrG after training (P <
      0.05). Eight weeks of high-intensity intermittent running training enhanced
      resting pulmonary function and led to deeper exercise ventilation reflecting a
      better effectiveness in prepubescent children.

PMID- 15843958
TI  - Leg vascular resistance increases during head-up tilt in paraplegics.
AB  - Despite loss of centrally mediated sympathetic vasoconstriction to the legs,
      spinal cord-injured individuals cope surprisingly well with an orthostatic
      challenge. This study assessed changes in leg vascular resistance following head
      up tilt in healthy (C) and in paraplegic (P) individuals. After 10 min of supine
      rest, subjects were tilted 30 degrees head-up. Mean arterial pressure (MAP) and
      total peripheral resistance (TPR) increased in C (MAP from 76.7 +/ -6.6 mmHg to
      80.6 +/- 8.2 mmHg; TPR from 1.12 +/- 0.26 AU to 1.19 +/ -0.31 AU) while both
      remained unchanged in P. Echo Doppler ultrasound determined red blood cell
      velocity in the femoral artery, which decreased (P from 18.9+/-6.2 cm/s to 12.5
      +/- 4.5 cm/s, P = 0.001; C from 16.3 +/- 6.2 cm/s to 10.8 +/- 5.0 cm/s, P =
      0.001) and leg vascular resistance, which increased (P from 402 +/- 137 AU to 643
      +/- 274 AU, P = 0.001; C from 238 +/- 68 AU to 400 +/- 122 AU, P = 0.003) from
      supine to upright. The present study shows that independent of supraspinal
      sympathetic control, humans are able to increase leg vascular resistance and
      maintain blood pressure during head-up tilt.

PMID- 15843959
TI  - Static balance improvement in elderly after dorsiflexors electrostimulation
      training.
AB  - The purpose of the present study was to determine the effect of dorsiflexors'
      ElectroStimulation (ES) training, on postural tasks of increasing difficulty in
      the elderly. Twenty-one elderly adults were randomly assigned into one of two
      groups: a Training (TG) and a Control Group (CG). The TG (n = 10) performed (4
      weeks, 4 s/week, 40 min/session) superimposed (electrically evoked and voluntary
      activation) isometric dorsiflexions (ankle 100 degrees ) while seated. Biphasic,
      rectangular symmetrical pulses (300 ms, 70 Hz, 20-60 mA) were used to provoke
      maximal muscle activation. Participants performed three static balance tasks
      (Normal Quiet Stance, Sharpened Romberg, and One-Legged Stance) during which
      postural sway was quantified using maximum range and standard deviation of Centre
      of Pressure displacement (Kistler 9281C, 1,000 Hz). Bipolar surface electrodes
      were used to record the Electromyographic activity (EMG) of Tibialis Anterior,
      Medial Gastrocnemius, Rectus Femoris and Semi-Tendineous. Two-dimensional
      kinematic data were collected (60 Hz) and analyzed using the APAS Motion Analysis
      software. The body was modeled as a five-segment rigid link system. Isometric
      dorsiflexion moment/angular position relationship was also established using a
      Cybex dynamometer. ES training resulted in decreased postural sway (P < 0.05),
      greater ankle muscles EMG activity (P < 0.001), greater stability of the ankle
      joint (P < 0.05) and significant changes in mean position of all three joints of
      the lower limb. In addition, dorsiflexion moment significantly (P < 0.001)
      increased as a result of ES training. It is concluded that dorsiflexors' ES
      training, could reduce postural sway and the use of ankle muscles, more
      characteristic of young adults, might appear in the elderly as well.

PMID- 15843960
TI  - Are the effects of training on fat metabolism involved in the improvement of
      performance during high-intensity exercise?
AB  - The objective of the present study was to relate changes in certain muscle
      characteristics and indicators of metabolism in response to endurance training to
      the concomitant changes in time to exhaustion (T(lim)) at a work rate
      corresponding to maximal oxygen uptake VO(2speak). Eight healthy sedentary
      subjects pedalled on a cycle ergometer 2 h a day, 6 days a week, for 4 weeks.
      Training caused increases in VO(2peak) (by 8%), T(lim) (from 299 +/- 23 s before
      to 486 +/- 63 s after training), citrate synthase and 3-hydroxyl-acyl-CoA
      dehydrogenase (HAD) activities (by 54% and 16%, respectively) and capillary
      density (by 31%). Decreases in activity of lactate dehydrogenase (LDH) and muscle
      type of LDH (by 24% and 28%, respectively) and the phosphofructokinase/citrate
      synthase ratio (by 37%) were also observed. Respiratory exchange ratio (RER)
      tended to be lower (P < 0.1) at all relative work rates after training while the
      corresponding ventilation rates (VE) were unchanged. At the same absolute work
      rate, RER and (VE) were lower after training (P < 0.05). The improvement of
      T(lim) with training was related to the increases in HAD activity (r = 0.91, P =
      0.0043), and to the decreases in RER calculated for Pa(peak) (r = 0.71, P =
      0.0496). The present results suggest that the training-induced adaptations in fat
      metabolism might influence T(lim) at a work rate corresponding to VO(2peak) and
      stimulate the still debated and incompletely understood role of fat metabolism
      during short high-intensity exercise.

PMID- 15843962
TI  - Lateral diffusion of CO2 in leaves of the crassulacean acid metabolism plant
      Kalanchoe daigremontiana Hamet et Perrier.
AB  - Dynamic patchiness of photosystem II (PSII) activity in leaves of the
      crassulacean acid metabolism (CAM) plant Kalanchoe daigremontiana Hamet et
      Perrier, which was independent of stomatal control and was observed during both
      the day/night cycle and circadian endogenous oscillations of CAM, was previously
      explained by lateral CO2 diffusion and CO2 signalling in the leaves [Rascher et
      al. (2001) Proc Natl Acad Sci USA 98:11801-11805; Rascher and Luttge (2002) Plant
      Biol 4:671-681]. The aim here was to actually demonstrate the importance of
      lateral CO2 diffusion and its effects on localized PSII activity. Covering small
      sections of entire leaves with silicone grease was used for local exclusion of a
      contribution of atmospheric CO2 to internal CO2 via transport through stomata. A
      setup for combined measurement of gas exchange and chlorophyll fluorescence
      imaging was used for recording photosynthetic activity with a spatiotemporal
      resolution. When remobilization of malic acid from vacuolar storage and its
      decarboxylation in the CAM cycle caused increasing internal CO2 concentrations
      sustaining high PSII activity behind closed stomata, PSII activity was also
      increased in adjacent leaf sections where vacuolar malic acid accumulation was
      minimal as a result of preventing external CO2 supply due to leaf-surface
      greasing, and where therefore CO2 could only be supplied by diffusion from the
      neighbouring malic acid-remobilizing leaf tissue. This demonstrates lateral CO2
      diffusion and its effect on local photosynthetic activity.

PMID- 15843961
TI  - Fungal pathogen-induced changes in the antioxidant systems of leaf peroxisomes
      from infected tomato plants.
AB  - Peroxisomes, being one of the main organelles where reactive oxygen species (ROS)
      are both generated and detoxified, have been suggested to be instrumental in
      redox-mediated plant cell defence against oxidative stress. We studied the
      involvement of tomato (Lycopersicon esculentum Mill.) leaf peroxisomes in defence
      response to oxidative stress generated upon Botrytis cinerea Pers. infection. The
      peroxisomal antioxidant potential expressed as superoxide dismutase (SOD, EC
      1.15.1.1), catalase (CAT, EC 1.11.1.6) and glutathione peroxidase (GSH-Px, EC
      1.11.1.19) as well as the ascorbate-glutathione (AA-GSH) cycle activities was
      monitored. The initial infection-induced increase in SOD, CAT and GSH-Px
      indicating antioxidant defence activation was followed by a progressive
      inhibition concomitant with disease symptom development. Likewise, the activities
      of AA-GSH cycle enzymes: ascorbate peroxidase (APX, EC 1.11.1.11),
      monodehydroascorbate reductase (MDHAR, EC 1.6.5.4), dehydroascorbate reductase
      (DHAR, EC 1.8.5.1) and glutathione reductase (GR, EC 1.6.4.2) as well as
      ascorbate and glutathione concentrations and redox ratios were significantly
      decreased. However, the rate and timing of these events differed. Our results
      indicate that B. cinerea triggers significant changes in the peroxisomal
      antioxidant system leading to a collapse of the protective mechanism at advanced
      stage of infection. These changes appear to be partly the effect of pathogen
      promoted leaf senescence.

PMID- 15843963
TI  - Changes in gene expression during dehardening of cold-hardened winter rye (Secale
      cereale L.) leaves and potential role of a peptide methionine sulfoxide reductase
      in cold-acclimation.
AB  - Suppression subtractive hybridization and differential display polymerase chain
      reactions were used to identify genes that were differentially expressed in cold
      hardened and dehardened leaves of winter rye (Secale cereale L.). The transcripts
      of nine genes declined during dehardening at 22 degrees C of cold-hardened 4
      degrees C-grown leaves, indicating some role in cold-acclimation. Among the genes
      that were strongly expressed in cold-hardened leaves were five genes of
      photosynthetic metabolism, the gene of the antioxidative enzyme peptide
      methionine sulfoxide reductase (PMSR) and three genes of RNA and protein
      metabolism. Four genes were identified that were more strongly expressed during
      dehardening of cold-hardened leaves at 22 degrees C. A full-length cDNA for a
      presumed cytosolic PMSR (EC 1.8.4.6) of rye leaves was identified. After
      heterologous expression in Escherichia coli, an antiserum against the ScPMSR was
      produced. The content of the ScPMSR protein, visualized by immunoblotting, was
      much higher in cold-hardened than in non-hardened leaves and declined during
      dehardening. In non-hardened leaves the mRNA of ScPMSR increased only slowly
      during exposures to 4 degrees C in light and was not affected by exposure to 4
      degrees C in darkness. However, the ScPMSR mRNA was also induced by prolonged
      exposure (48 h) to high light at 22 degrees C, or by treatment with 2 muM
      paraquat. Consequently, the induction of cytosolic ScPMSR is a late response to
      prolonged photooxidative stress conditions, as expected during growth at low
      temperature in light. In cold-hardened leaves, PMSR may protect proteins from
      photodamage and thus prevent their degradation and the need for repair.

PMID- 15843964
TI  - Cytokinin-induced hypocotyl elongation in light-grown Arabidopsis plants with
      inhibited ethylene action or indole-3-acetic acid transport.
AB  - Cytokinins inhibit hypocotyl elongation in darkness but have no obvious effect on
      hypocotyl length in the light. However, we found that cytokinins do promote
      hypocotyl elongation in the light when ethylene action is blocked. A 50% increase
      in Arabidopsis thaliana (L.) Heynh. hypocotyl length was observed in response to
      N6-benzyladenine (BA) treatment in the presence of Ag+. The level of the ethylene
      precursor 1-aminocyclopropane-1-carboxylic acid was strongly increased,
      indicating that ethylene biosynthesis was up-regulated by treatment with
      cytokinin. Furthermore, the effects of cytokinins on hypocotyl elongation were
      also tested using a series of mutants in the cascade of the ethylene-signal
      pathway. In the ethylene-insensitive mutants etr1-3 and ein2-1, cytokinin
      treatment resulted in hypocotyl lengths comparable to those of wild-type
      seedlings treated with both Ag+ and BA. A similar phenotypical response to
      cytokinin was observed when auxin transport was blocked by alpha
      naphthylphthalamic acid (NPA). Applied cytokinin largely restored cell elongation
      in the basal and middle parts of the hypocotyls of NPA-treated seedlings and at
      the same time abolished the NPA-induced decrease in indole-3-acetic acid levels.
      Our data support the hypothesis that, in the light, cytokinins interact with the
      ethylene-signalling pathway and conditionally up-regulate ethylene and auxin
      synthesis.

PMID- 15843965
TI  - Blue-light-induced reorganization of the actin cytoskeleton and the avoidance
      response of chloroplasts in epidermal cells of Vallisneria gigantea.
AB  - In leaf epidermal cells of the aquatic angiosperm Vallisneria gigantea Graebner,
      high-intensity blue light induces the actin-dependent avoidance response of
      chloroplasts. By semi-quantitative motion analysis and phalloidin staining, time
      courses of the blue-light-induced changes in the mode of movement of individual
      chloroplasts and in the configuration of actin filaments were examined in the
      presence and absence of a flavoprotein inhibitor, diphenylene iodonium. In dark
      adapted cells, short, thick actin bundles seemed to surround each chloroplast,
      which was kept motionless in the outer periclinal cytoplasm of the cells. After
      10 min of irradiation with high-intensity blue light, a rapid, unidirectional
      movement of chloroplasts was induced, concomitant with the appearance of
      aggregated, straight actin bundles stretched over the outer periclinal cytoplasm.
      Diphenylene iodonium inhibited the avoidance response of chloroplasts, apparently
      by delaying a change in the mode of chloroplast movement from random sway to
      unidirectional migration, by suppressing the appearance of aggregated, straight
      actin bundles. In partially irradiated individual cells, redistribution of
      chloroplasts and reorganization of actin filaments occurred only in the areas
      exposed to blue light. From the results, we propose that the short, thick actin
      bundles in the vicinity of chloroplasts function to anchor the chloroplasts in
      dark-adapted cells, and that the aggregated, straight actin bundles organized
      under blue-light irradiation provide tracks for unidirectional movement of
      chloroplasts.

PMID- 15843966
TI  - Systemic induction of traumatic resin ducts and resin flow in Austrian pine by
      wounding and inoculation with Sphaeropsis sapinea and Diplodia scrobiculata.
AB  - The potential role of the resin system in the response of Austrian pine (Pinus
      nigra Arn.) seedlings to mechanical injury and fungal infection was studied in
      greenhouse experiments. Anatomical observations were performed on 2-year-old
      plants wounded at collar level and inoculated with Sphaeropsis sapinea (Fr.: Fr.)
      Dyko & Sutton in Sutton or Diplodia scrobiculata (J. de Wet, B. Slippers & M. J.
      Wingfield, sp. nov.; sensu de Wet et al. 2003), two fungal pathogens that cause
      shoot blight and canker on conifers, and that are characterized by different
      levels of aggressiveness. Histological examination of host tissue taken from the
      stem at 0, 8, and 12 cm above the treatment site revealed significant treatment-
      and time-dependent effects on the course of locally and systemically induced
      traumatic resin duct (TRD) development. Occurrence of TRDs was observed after 4
      days only in seedlings inoculated with D. scrobiculata. At 12 days, TRDs were
      present also in mock-inoculated controls. No TRDs appeared in seedlings
      inoculated with S. sapinea. However, S. sapinea caused loss of vacuolar
      phenolics, severe disruption of cambial tissue and invaded the host xylem quickly
      and apparently unimpeded, whereas D. scrobiculata was never detected in the host
      xylem. Five-year-old Austrian pines subjected to the same stem base treatments
      were used to determine the resin mass flowing from the stem 30 cm above the
      treatment sites. Wounding and/or inoculation induced a significant, 8.3-fold
      average increase in systemic resin flow over the untreated trees 3 weeks after
      basal treatment, suggesting that wounding is the sole prerequisite for systemic
      induction of resin flow. The results are discussed in the context of current
      disease resistance models.

PMID- 15843967
TI  - Transgenic expression of the von Willebrand A domain of the BONZAI 1/COPINE 1
      protein triggers a lesion-mimic phenotype in Arabidopsis.
AB  - The copines are a newly identified, widely distributed class of Ca(2+)-dependent,
      phospholipid-binding proteins that may be involved in cellular signaling. The
      copines have a characteristic domain structure: two C2 domains in the N-terminal
      region and a von Willebrand A (VWA) domain in the C-terminal region. Studies
      suggest that copines interact with target protein(s) via their VWA domain and
      recruit the proteins to a membrane location through the activity of the C2
      domains. Arabidopsis thaliana (L.) Heynh. plants with loss-of-function mutations
      in the BONZAI 1/COPINE 1 (BON1/CPN1) gene display aberrant regulation of defense
      responses, including development of a lesion-mimic phenotype, an accelerated
      hypersensitive response, and increased resistance to a bacterial and an
      oomycetous pathogen. The phenotype of mutants in BON1/CPN1 is both humidity- and
      temperature-sensitive. In this study, we generated transgenic plants expressing
      either the VWA or the C2 portions of BON1/CPN1 in the wild-type Columbia-0 (Col
      0) genetic background. Transgenic plants expressing the BON1/CPN1 C2 domain
      portion appeared like wild-type plants. However, transgenic plants expressing the
      BON1/CPN1 VWA domain exhibited a lesion-mimic phenotype that partially
      phenocopied bon1/cpn1 mutant plants. Our data suggest that BON1/CPN1 VWA domain
      fragments may interfere with the function of the full-length endogenous BON1/CPN1
      protein, possibly by competing with the full-length BON1/CPN1 protein for
      association with target proteins normally bound to the full-length BON1/CPN1
      protein.

PMID- 15843969
TI  - Health-related quality of life assessment by the EuroQol-5D can provide cost
      utility data in the field of low-back surgery.
AB  - There is limited data on the cost-utility of low-back surgical procedures. The
      EuroQol-5D (EQ-5D) is a generic health-related quality of life (HRQL) instrument,
      which was designed for cost-utility analyses and for comparisons of therapeutic
      effects across different diseases. Disease-specific (HRQL) instruments cannot be
      used for such purposes. However, there is little evidence of the usefulness of
      the EQ-5D in the field of low-back surgery, and it might be too general to assess
      specific conditions. We therefore tested its validity and responsiveness against
      a widely used disease-specific HRQL instrument [the Oswestry disability index
      (ODI)], in a prospective study on 326 patients operated for degenerative
      disorders in the lumbar spine. The reliability of the EQ-5D was also evaluated.
      Follow-up time was 12 months. Cross-sectional construct validity of the EQ-5D and
      ODI in the assessments of pain, functional status, health state and employment
      status were equal. The ODI performed better only in the assessment of walking
      capability. Only small differences in responsiveness were found. The reliability
      of the EQ-5D was solid. Our results indicate that the EQ-5D is useful for
      estimating health state values and for monitoring outcome of patients undergoing
      low-back surgery. Hence, this instrument would provide valid data for cost
      utility analyses.

PMID- 15843968
TI  - Transcriptional profiling of Saccharomyces cerevisiae cells under adhesion
      inducing conditions.
AB  - The ability to adhere to other cells is one of the most prominent determinants of
      fungal pathogenicity. Thus, adherence of fungi to human tissues or plastics
      triggers hospital-acquired fungal infections, which are an increasing clinical
      problem, especially in immunocompromised persons. In the model fungus
      Saccharomyces cerevisiae adhesion can be induced by starvation for amino acids,
      and depends on the transcriptional activator of the general amino acid control
      system, Gcn4p. However, not much is known about the transcriptional program that
      mediates adhesive growth under such conditions. In this study, we present a
      genome-wide transcriptional analysis of Sigma1278b yeast cells that were
      subjected to adhesion-inducing conditions imposed by amino acid starvation.
      Twenty-two novel genes were identified as inducible by amino acid starvation; 72
      genes belonging to different functional groups, which were not previously known
      to be regulated by Gcn4p, require Gcn4p for full transcriptional induction under
      adhesion-inducing conditions. In addition, several genes were identified in
      Sigma1278b cells that were inducible by amino acid starvation in a Gcn4p
      independent manner. Our data suggest that adhesion of yeast cells induced by
      amino acid starvation is regulated by a complex, Sigma1278b-specific
      transcriptional response.

PMID- 15843970
TI  - Modified triangular posterior osteosynthesis of unstable sacrum fracture.
AB  - We report preliminary results for unstable sacral fractures treated with a
      modified posterior triangular osteosynthesis. Seven patients were admitted to our
      trauma center with an unstable sacral fracture. The average age was 31 years (22
      41). There were four vertical shear lesions of the pelvis and three transverse
      fracture of the upper sacrum. The vertical shear injuries were initially treated
      with an anterior external fixator inserted at the time of admission. Definitive
      surgery was performed at a mean time of 9 days after trauma. The operation
      consisted in a posterior fixation combining a vertebropelvic distraction
      osteosynthesis with pedicle screws and a rod system, whereby the transverse
      fixation was obtained using a 6 mm rod as a cross-link between the two main rods.
      Late displacement of the posterior pelvis or fracture was measured on X-ray films
      according to the criteria of Henderson. The patients were followed-up for a
      minimum time of 12 months. Four patients who presented with a pre-operative
      perineal neurological impairment made a complete recovery. No iatrogenic nerve
      injury was reported. One case of deep infection was managed successfully with
      surgical debridement and local antibiotics. All patients complained of symptoms
      related to the prominence of the iliac screws. The metalwork was removed in all
      cases after healing of the fracture, at a mean time of 4.3 months after surgery.
      No loss of reduction of fracture was seen at final radiological follow-up. The
      preliminary results are promising. The fixation is sufficiently stable to allow
      an immediate progressive weight-bearing, and safe nursing care in polytrauma
      cases. The only problem seems to be related to prominent heads of the distal
      screws.

PMID- 15843971
TI  - Experimental study of the participation of the vertebral endplate in the
      integration of bone grafts.
AB  - The surgical technique of anterior vertebral arthrodesis has been modified by the
      introduction of cages in spinal surgery. The classical technique recommends
      removal of the vertebral endplate and exposure of bleeding cancellous bone.
      However, after the observation of cage subsidence during postoperative follow-up,
      the vertebral endplate is no longer removed, due to its greater mechanical
      resistance which can prevent cage subsidence. The mechanical characteristics of
      the vertebral endplate are well known, in contrast to its osteogenic potential,
      which was investigated in the present experimental study. The study was conducted
      on mongrel dogs of both sexes, which were submitted to anterior corpectomy at the
      cervical spine level. A cortico-cancellous bone graft removed from the tibia was
      used for the reconstruction of the vertebral segment, which was used with
      osteosynthesis plates. At the site of contact between the surface of the
      vertebral body and the bone graft, the vertebral endplate was completely removed
      and cancellous bone was exposed in the inferior vertebra, whereas in the superior
      vertebra of the arthrodesed vertebral segment only curettage was performed, and
      the vertebral endplate was preserved, as recommended for cage implantation.
      Twenty adult dogs of both sexes were divided into four experimental groups
      according to time of sacrifice (15, 30, 90, and 180 days). The consolidation of
      the bone graft with the vertebral body was evaluated by histology using
      hematoxilin-eosin and Gomori trichrome staining. In the interface between the
      bone graft and the vertebral body surface in which the vertebral endplate was not
      removed, graft consolidation was not observed in any of the group I animals
      (sacrificed after 15 days), and was observed in 1/5 animals of group II (30
      days), in 2/5 animals of group III (90 days), and in 4/5 animals of group IV (180
      days). In the interface between the graft and the vertebral body in which the
      vertebral endplate was removed, bone-graft consolidation was observed in all
      animals of all experimental groups (15, 30, 90, and 180 days). Bone-graft
      consolidation with the surface of the vertebral body was influenced by the
      removal or maintenance of the vertebral endplate. Due to the importance of this
      structure in current surgical procedures, this phenomenon deserves to be studied
      in more detail in order to understand the basic events involved in this process.

PMID- 15843972
TI  - Subsidence after anterior lumbar interbody fusion using paired stand-alone
      rectangular cages.
AB  - The authors conducted a study to determine at what stage after surgery the
      subsidence occurred, and to assess the relationships of radiographic fusion and
      the recurrence of symptoms with the development of subsidence. Ninety patients
      underwent a single-level anterior lumbar interbody fusion (ALIF) using paired
      stand-alone rectangular cages between November 2000 and June 2002. All patients
      had regular clinical or imaging follow-up for a minimum of 19 months (range 19-38
      months, mean = 27 months). The ratio of male to female patients was 1:3.1. The
      patients' ages at the time of ALIF ranged from 25 to 72 years, with a mean of 53
      years. The preoperative and postoperative intervertebral disc heights were
      serially measured by plain radiographs. The location of cage subsidence into the
      vertebral body and times until the presence of subsidence were also assessed. The
      mean preoperative intervertebral disc height was 11.6+/-3.1 mm, which spread
      immediately after surgery to 16.9+/-2.0 mm. This increase was statistically
      significant (P = 0.001). At the last follow-up visit, the mean intervertebral
      disc height had been reduced to 13.2+/-2.4 mm. Sixty-nine of 90 patients (76.7%)
      developed cage subsidence into the surrounding vertebral body. Subsidence was
      more often noted in the superior endplate above the cage with regard to the
      location of cage subsidence [superior endplate: 27 patients (39.1%), inferior
      endplate: 12 patients (17.3%), both: 30 patients (43.6%)]. The onset of
      subsidence varied from 0.25 to 8 months after surgery (median, 2.75 months). The
      8-, 12-, and 16-week actuarial rates for developing cage subsidence were 38.9,
      63.4, and 70.7%, respectively, when using the Kaplan-Meier method. There was no
      statistical correlation between the recurrence of symptoms (P = 0.3952) and
      radiographic fusion (P = 0.9518) with the log-rank test in development of
      subsidence. This study demonstrates that cage subsidence is an expected
      occurrence after ALIF using stand-alone rectangular cages. The 3- and 4-month
      actuarial rates for developing cage subsidence were 63.4 and 70.7%, respectively,
      and cage subsidence had no correlation with recurrence of symptoms and
      radiographic fusion in our study.

PMID- 15843973
TI  - Development of spinal posture in a cohort of children from the age of 11 to 22
      years.
AB  - Spinal posture and the resultant changes during the entire pubertal growth period
      have not been reported previously. No cohort study has focused on the development
      of spinal posture during both the ascending and the descending phase of peak
      growth of the spine. The growth and development of a population-based cohort of
      1060 children was followed up for a period of 11 years. The children were
      examined 5 times, at the ages of 11, 12, 13, 14 and 22 years. A total of 430
      subjects participated in the final examination. Sagittal spinal profiles were
      determined using spinal pantography by the same physician throughout the study.
      Thoracic kyphosis was more prominent in males at all examinations. The increasing
      tendency towards thoracic kyphosis continued in men, but not in women. The degree
      of lumbar lordosis was constant during puberty and young adulthood. Women were
      more lordotic at all ages. Thoracic hyperkyphosis of > or =45 degrees was as
      prevalent in boys as girls at 14 years, but significantly (P<0.0001) more
      prevalent in men (9.6%) than in women (0.9%) at 22 years. The degree of mean
      thoracic kyphosis and the prevalence of hyperkyphosis increased in men during the
      descending phase of peak growth of the spine, but decreased in women.

PMID- 15843974
TI  - Production and purification of a calcium-dependent protease from Bacillus cereus
      BG1.
AB  - The production and purification of a calcium-dependent protease by Bacillus
      cereus BG1 were studied. The production of the protease was found to depend
      specifically on the calcium concentration in the culture medium. This suggests
      that this metal ion is essential for the induction of protease production and/or
      stabilisation of the enzyme after synthesis. The calcium requirement is highly
      specific since other metal ions (such as Mg(2+) and Ba(2+), which both activate
      the enzyme) are not able to induce protease production. The most appropriate
      medium for growth and protease production comprises (g L(-1)) starch 5, CaCl(2)
      2, yeast extract 2, K(2)HPO(4) 0.2 and KH(2)PO(4) 0.2. The protease of BG1 strain
      was purified to homogeneity by ultrafiltration, heat treatment, gel filtration on
      Sephacryl S-200, ion exchange chromatography on DEAE-cellulose and, finally, a
      second gel filtration on Sephacryl S-200, with a 39-fold increase in specific
      activity and 23% recovery. The molecular weight was estimated to be 34 kDa on SDS
      PAGE. The optimum temperature and pH of the purified enzyme were determined to be
      60 degrees C and 8.0, respectively, in 100 mM Tris-HCl buffer + 2 mM CaCl(2).

PMID- 15843976
TI  - Estimation of muscle spindle information rate by pattern matching and the effect
      of gamma system activity on parallel spindles.
AB  - The information transmission properties of ensembles of MSs and the effect of the
      gamma system on these properties were studied. Three converging lines of research
      were taken: (1) the development of information theoretic estimation tools, and
      the formulation of an "operational" interpretation for the information rate; (2)
      animal experiments in which the mutual information rate was estimated and the
      effect of the gamma system was quantified; (3) simulation of a muscle spindle
      model with gamma activation in order to corroborate the results of the animal
      experiments. The main hypothesis was that the gamma system will enhance
      information theoretic measures that quantify the quality of the sensory neural
      channel comprised from an ensemble of primary muscle spindle afferents. A random
      stimulus was applied to a muscle in the hind limb of a cat, while spike trains
      from several primary MS afferents were recorded simultaneously. The stimulus was
      administered twice, with an operative and a disconnected gamma system. The mutual
      information rate between the stimulus and spike trains, as well as other
      information theoretic measures, was estimated. The information rate of ensembles
      of MSs increased with increasing ensemble size. However, with an operative gamma
      system the "ensemble effect" was much higher. In addition, the ensemble effect
      was influenced by the stimulus spectrum. A muscle spindle population model with
      gamma activation was simulated with stimuli that were identical to that of the
      animal experiments. The simulation results supported the experimental results and
      corroborated the main hypothesis. The results indicate that the gamma system has
      an important role in enhancing information transmission from ensembles of MSs to
      the spinal cord.

PMID- 15843975
TI  - Monitoring of microbial souring in chemically treated, produced-water biofilm
      systems using molecular techniques.
AB  - The identification of bacteria in oil production facilities has previously been
      based on culture techniques. However, cultivation of bacteria from these often
      extreme environments can lead to errors in identifying the microbial community
      members. In this study, molecular techniques including fluorescence in situ
      hybridization, PCR, denaturing gradient gel electrophoresis, and sequencing were
      used to track changes in bacterial biofilm populations treated with nitrate,
      nitrite, or nitrate+molybdate as agents for the control of sulfide production.
      Results indicated that nitrite and nitrate+molybdate reduced sulfide production,
      while nitrate alone had no effect on sulfide generation. No long-term effect on
      sulfide production was observed. Initial sulfate-reducing bacterial numbers were
      not influenced by the chemical treatments, although a significant increase in
      sulfate-reducing bacteria was observed after termination of the treatments.
      Molecular analysis showed a diverse bacterial population, but no major shifts in
      the population due to treatment effects were observed.

PMID- 15843977
TI  - Congenital atresia of the left main coronary artery: successful surgical
      treatment (myocardial revascularisation and mitral valve repair) in a 1-year-old
      boy.

PMID- 15843978
TI  - Apnoea and bradycardia in preterm infants following immunisation with pentavalent
      or hexavalent vaccines.
AB  - There is a lack of data regarding the incidence and clinical significance of
      apnoea or bradycardia (AB) following immunisation with combination vaccines
      containing an acellular pertussis (Pa) component in respiratory stable preterm
      infants. Medical records of respiratory stable preterm infants who received a
      first dose of a combined diphtheria (D) and tetanus (T) toxoids, Pa, Haemophilus
      influenzae type b (Hib), inactivated poliovirus (IPV) vaccine with or without
      hepatitis B virus (HBV) in the neonatal intensive care unit (NICU) of the
      University Children's Hospital Basel between January 2000 and June 2003 were
      analysed. For each infant, clinical data were recorded for a 72 h period before
      and after immunisation. Of 53 infants with a mean gestational age of 28 weeks, 7
      (13%) showed a transient recurrence of or increase in episodes of AB following
      immunisation. Five of these seven infants required intervention ranging from
      tactile stimulation to bag and mask ventilation. Regarding risk factors, children
      with recurrent or increased AB were indistinguishable from those without such
      events. The rate of fever (>38 degrees C) following immunisation was higher in
      affected infants compared to those without recurrence of or increase in AB (3/7
      vs 2/46, P = 0.01). CONCLUSION: Although most infants tolerated immunisation
      well, the incidence of recurrent or increased apnoea or bradycardia in
      respiratory stable preterm infants following the first immunisation with penta-
      or hexavalent vaccines was 13%. Most apnoea or bradycardia events required
      intervention but did not have serious consequences. Monitoring of all preterm
      infants following immunisation in the neonatal intensive care unit is
      recommended.

PMID- 15843979
TI  - 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene in
      children with systemic meningococcaemia.
AB  - Meningococcal disease may present as sepsis, meningitis or a combination of both.
      Impaired fibrinolysis and massive elevation of the plasminogen activator
      inhibitor-1 (PAI-1) is a characteristic feature of meningococcal sepsis.
      Previously, an association between mortality and the functional 4G/5G promoter
      polymorphism of the PAI-1gene in a cohort of UK and Dutch children with
      meningococcal sepsis was reported. We carried out a prospective, multicentre
      study to investigate the association of the 4G/5G PAI-1 polymorphism, diagnosis,
      and outcome in meningococcal disease in a Central European and UK population.
      Blood samples and clinical information of 347 previously healthy children with
      meningococcal infection were collected from 95 paediatric hospitals in Germany,
      Switzerland, Italy, the United Kingdom, and Austria from 2000 until 2002.
      Mortality was significantly associated with the 4G/4G genotype (12 of 90 (13%)
      vs. 15 of 240 (6%), P = 0.037), resulting in an odds ratio of 2.31. The diagnosis
      of sepsis (independent of symptoms of meningitis) was significantly more frequent
      in carriers of the 4G/4G genotype (P = 0.01), resulting in an odds ratio of 2.21
      to develop sepsis. Meningitis was not associated with the PAI-1 4G/5G
      polymorphism, and allele frequencies were similar in patient and control groups.
      CONCLUSION: Our data show a correlation between the 4G/4G genotype in the
      plasminogen activator inhibitor-1 gene and poor outcome in children with
      meningococcal infection. In addition, 4G homozygous patients were prone to
      develop sepsis. We found no influence of the plasminogen activator inhibitor-1
      polymorphism on the susceptibility to invasive meningococcal infection.

PMID- 15843980
TI  - Implantable cardioverter defibrillator implantation in children in The
      Netherlands.
AB  - To evaluate the indications, underlying cardiac disorders, efficacy and
      complications involved with implantable cardioverter-defibrillators (ICDs) in
      paediatric patients in The Netherlands, the records of all patients aged 18 years
      or younger who underwent ICD placement were reviewed retrospectively. Between
      January 1995 and September 2002, 23 patients (11 males, 12 females; median age 12
      years, range 6 months to 16 years) underwent ICD implantation. The ICD was
      implanted for aborted sudden cardiac death ( n = 14), syncope ( n = 5) or for
      primary prevention of sudden cardiac death ( n = 4). Underlying cardiac disorders
      were electrical diseases ( n = 16), hypertrophic or dilated cardiomyopathy ( n =
      4) and congenital cardiac malformations ( n = 3). Five patients had an
      epicardially placed ICD, while 18 underwent a transvenous approach. The generator
      was placed in an abdominal position in eight patients, whereas it was placed in
      the subpectoral region in 15. There was no early mortality. Median hospital stay
      was 5 days (range 2-30 days). Median follow-up time was 29 months (range 1 month
      to 7 years). Seven patients experienced an inappropriate shock after a median
      period of 7 months; five patients an appropriate shock after a median period of 3
      months. The reasons for inappropriate shock were supraventricular tachycardia ( n
      = 1), sinus tachycardia ( n = 4) or T-wave sensing (n = 2). One patient with
      malignant long QT syndrome died of intractable arrhythmias and irreversible
      cardiomyopathy. Generator replacement was necessary in four patients after 28,
      44, 51 and 54 months respectively. CONCLUSION: Implantable cardioverter
      defibrillator implantation in paediatric patients is a safe procedure with a good
      medium-term outcome. The most serious problem is the occurrence of a significant
      number of inappropriate shocks.

PMID- 15843981
TI  - A 12-month-old boy with high fever, erythematous lesions and haemorrhagic oedema.

PMID- 15843982
TI  - Radiographic inguinal curl may indicate paraspinal misplacement of percutaneously
      inserted central venous catheters: report of three cases.
AB  - BACKGROUND: Misplacement of percutaneously inserted central venous catheters
      (PCVCs) into the paraspinal venous plexus can result in devastating outcomes.
      Several cases have been reported in the literature together with an explanation
      of the mechanism. OBJECTIVE: To describe three premature babies with their PCVCs
      inserted through the left saphenous vein that ended up in the lumbar spinal dural
      venous plexus. RESULTS: Plain radiographs obtained to check positions showed an
      unusual 360 degrees curl of the PCVC in the left inguinal area. CONCLUSION: We
      believe that misplacement of the catheter into the paraspinal venous plexus could
      be diagnosed with great accuracy if such a curl is seen.

PMID- 15843984
TI  - Computational studies on imidazole heme conformations.
AB  - Density functional theory computations of heme with ionized propionic acid
      groups, axially coordinated with two imidazoles, were performed for different
      mutual orientations of the imidazole planes. Environmental influences from water
      or protein were considered with a continuum dielectric medium by solving the
      Poisson equation. In vacuum, optimized geometries yielded imidazole-heme
      conformations where the NH groups of imidazoles are oriented toward the heme
      propionic groups in agreement with data from crystal structures of heme proteins.
      Conformational free-energy dependencies of the mutual orientation of axially
      ligated imidazoles calculated in protein (epsilon=10) and water (epsilon=80)
      environments confirmed the vacuum results, albeit the energy difference between
      the preferred and the 180 degrees opposite orientations of the imidazole ligand
      decreased from 3.84 kcal/mol in vacuum to 2.35 and 2.40 kcal/mol in protein and
      water, respectively. Two main factors determine the imidazole orientation: (1)
      the direct intramolecular electrostatic interactions of propionic groups with the
      polar NH groups of imidazole and (2) the electrostatic interaction of the total
      dipole moment of the imidazole-heme complex with the reaction field. In vacuum,
      only the first type of interaction is present, while in a dielectric medium the
      latter effect becomes competitive at high dielectric constant, resulting in a
      decrease of the orientational preference. Interestingly, the orientational
      preference of the imidazole axially ligated to heme becomes even more pronounced,
      if the negatively charged propionates are neutralized by counter charges that
      mimic salt bridges or protonation of the propionates.

PMID- 15843985
TI  - A new heterobinuclear FeIIICuII complex with a single terminal FeIII-O(phenolate)
      bond. Relevance to purple acid phosphatases and nucleases.
AB  - A novel heterobinuclear mixed valence complex
      [Fe(III)Cu(II)(BPBPMP)(OAc)(2)]ClO(4), 1, with the unsymmetrical N(5)O(2) donor
      ligand 2-bis[{(2-pyridylmethyl)aminomethyl}-6-{(2-hydroxybenzyl)(2
      pyridylmethyl)}aminomethyl]-4-methylphenol (H(2)BPBPMP) has been synthesized and
      characterized. A combination of data from mass spectrometry, potentiometric
      titrations, X-ray absorption and electron paramagnetic resonance spectroscopy, as
      well as kinetics measurements indicates that in ethanol/water solutions an
      [Fe(III)-(mu)OH-Cu(II)OH(2)](+) species is generated which is the likely catalyst
      for 2,4-bis(dinitrophenyl)phosphate and DNA hydrolysis. Insofar as the data are
      consistent with the presence of an Fe(III)-bound hydroxide acting as a
      nucleophile during catalysis, 1 presents a suitable mimic for the hydrolytic
      enzyme purple acid phosphatase. Notably, 1 is significantly more reactive than
      its isostructural homologues with different metal composition (Fe(III)M(II),
      where M(II) is Zn(II), Mn(II), Ni(II), or Fe(II)). Of particular interest is the
      observation that cleavage of double-stranded plasmid DNA occurs even at very low
      concentrations of 1 (2.5 microM), under physiological conditions (optimum pH of
      7.0), with a rate enhancement of 2.7 x 10(7) over the uncatalyzed reaction. Thus,
      1 is one of the most effective model complexes to date, mimicking the function of
      nucleases.

PMID- 15843983
TI  - Mammalian sleep.
AB  - This review examines the biological background to the development of ideas on
      rapid eye movement sleep (REM sleep), so-called paradoxical sleep (PS), and its
      relation to dreaming. Aspects of the phenomenon which are discussed include
      physiological changes and their anatomical location, the effects of total and
      selective sleep deprivation in the human and animal, and REM sleep behavior
      disorder, the latter with its clinical manifestations in the human. Although
      dreaming also occurs in other sleep phases (non-REM or NREM sleep), in the human,
      there is a contingent relation between REM sleep and dreaming. Thus, REM is taken
      as a marker for dreaming and as REM is distributed ubiquitously throughout the
      mammalian class, it is suggested that other mammals also dream. It is suggested
      that the overall function of REM sleep/dreaming is more important than the
      content of the individual dream; its function is to place the dreamer
      protagonist/observer on the topographical world. This has importance for the
      developing infant who needs to develop a sense of self and separateness from the
      world which it requires to navigate and from which it is separated for long
      periods in sleep. Dreaming may also serve to maintain a sense of 'I'ness or
      "self" in the adult, in whom a fragility of this faculty is revealed in
      neurological disorders.

PMID- 15843986
TI  - Preliminary crystallographic analysis of the Cks protein p13(suc1P90AP92A) from
      Schizosacharromyces pombe.
AB  - The p13(suc1) is the fission yeast member of the Cks (Cdc28-dependant kinase
      subunit) family of proteins. The Cks proteins bind to and are required for the
      function of cyclin-dependant kinase (Cdk) proteins during cell cycle progression
      in eukaryotic cells. Two conformations of Cks have been detected
      crystallographically; a compact monomer with the C-terminal fourth beta-strand
      inserted into the core of the molecule between strands 2 and 3, and a strand
      exchanged dimer where the fourth beta-strand is inserted into the core of the
      dimer partner in an equivalent position. There is a highly conserved "hinge"
      region consisting of the motif PEP, N-terminal to the fourth beta-strand. In the
      monomer this motif constitutes a beta-turn, while in the dimeric structure it is
      extended, allowing strand exchange. The mutant protein p13(suc1P90AP92A), in
      which alanine residues replace both prolines of the turn, provides an opportunity
      to examine the role of the prolines in this hinge region and how they may allow
      for the formation of strand-exchanged dimers by Cks proteins. We have expressed
      and purified this mutant protein. Two millimolar p13(suc1P90AP92A) crystallised
      in 50 mM tris(hydroxymethyl)aminomethane pH 7.5, 30% poly(ethylene glycol) 1500.
      Diffraction data were collected at room temperature on an MAR345 image plate
      using Cu Kalpha radiation from a Rigaku RU200 rotating-anode generator source to
      2.70A. The crystal has unit cell parameters a=b=75.1 A, c=34.9 A, alpha=beta=90
      degrees , gamma=120 degrees. Diffraction data were indexed to the space group P6
      and systematic absences 00l indicate a screw axis consistent with P6(3).

PMID- 15843987
TI  - Staphylococcus aureus ClpYQ plays a minor role in stress survival.
AB  - Although bacteria lack the proteasome-ubiquitin proteolytic pathway, the
      homologue of the beta-type proteasome subunit, ClpQ, is highly conserved among
      bacterial species. ClpQ associates with its ATPase partner, ClpY, to form a two
      component protease, which also structurally resembles the 26S proteasome. Here we
      have disrupted clpQ and clpY of the versatile pathogen Staphylococcus aureus in
      order to examine the significance of the ClpYQ protease for growth under stress
      conditions. We found that the mutant, in contrast to the wild type, was unable to
      form colonies at very high temperatures. To our knowledge, this is the first
      described phenotype of ClpYQ in Gram-positive bacteria. However, in the presence
      of puromycin and under all other stress conditions, tested growth of the clpYQ
      mutant cells was similar to growth of the wild type. Additionally, the absence of
      ClpYQ did not affect virulence as measured by a murine skin abscess model.
      Transcriptional analysis revealed that clpQ and clpY are expressed as part of a
      four-cistronic operon encompassing xerC and codY, and that expression is modestly
      induced by heat. In conclusion, our data indicates that ClpYQ plays only a
      secondary role in the degradation of non-native proteins in S. aureus.

PMID- 15843988
TI  - The importance of modelling heterogeneity in complex disease: application to NIMH
      Schizophrenia Genetics Initiative data.
AB  - As for other complex diseases, linkage analyses of schizophrenia (SZ) have
      produced evidence for numerous chromosomal regions, with inconsistent results
      reported across studies. The presence of locus heterogeneity appears likely and
      may reduce the power of linkage analyses if homogeneity is assumed. In addition,
      when multiple heterogeneous datasets are pooled, inter-sample variation in the
      proportion of linked families (alpha) may diminish the power of the pooled sample
      to detect susceptibility loci, in spite of the larger sample size obtained. We
      compare the significance of linkage findings obtained using allele-sharing LOD
      scores (LOD(exp))-which assume homogeneity-and heterogeneity LOD scores (HLOD) in
      European American and African American NIMH SZ families. We also pool these two
      samples and evaluate the relative power of the LOD(exp) and two different
      heterogeneity statistics. One of these (HLOD-P) estimates the heterogeneity
      parameter alpha only in aggregate data, while the second (HLOD-S) determines
      alpha separately for each sample. In separate and combined data, we show
      consistently improved performance of HLOD scores over LOD(exp). Notably, genome
      wide significant evidence for linkage is obtained at chromosome 10p in the
      European American sample using a recessive HLOD score. When the two samples are
      combined, linkage at the 10p locus also achieves genome-wide significance under
      HLOD-S, but not HLOD-P. Using HLOD-S, improved evidence for linkage was also
      obtained for a previously reported region on chromosome 15q. In linkage analyses
      of complex disease, power may be maximised by routinely modelling locus
      heterogeneity within individual datasets, even when multiple datasets are
      combined to form larger samples.

PMID- 15843989
TI  - Genetic analysis of adiponectin and obesity in Hispanic families: the IRAS Family
      Study.
AB  - Adiponectin, coded for by the APM1 gene, is a novel adipocyte-derived hormone
      implicated in energy homeostasis and obesity. Several genetic studies have
      observed evidence of association between APM1 gene polymorphisms and features of
      the metabolic syndrome, such as insulin resistance and obesity. As part of a
      comprehensive genetic analysis of the APM1 gene, we have screened 96 unrelated
      individuals for polymorphisms in the promoter, coding regions, and 3'untranslated
      region (UTR). Three promoter single-nucleotide polymorphisms (SNPs), two rare
      coding SNPs (G113A and T1233C), and 13 SNPs in the 3'UTR were identified.
      Eighteen SNPs were genotyped in 811 Hispanic individuals from 45 families in the
      IRAS Family Study (IRASFS). SNPs were tested for association with six obesity
      quantitative traits (body mass index, waist, waist:hip ratio, subcutaneous
      adipose tissue, visceral adipose tissue, and visceral:subcutaneous ratio).
      Significant evidence of association to at least one of the obesity traits was
      identified in seven of the 18 SNPs (<0.001-0.05). The promoter SNP INS CA-11156
      was the most consistently associated SNP and was associated significantly with
      all measures of obesity, except the visceral:subcutaneous ratio (P-values 0.009
      0.03). Haplotype analysis supported this evidence of association, with haplotypes
      containing an insertion of one CA repeat at position -11156 consistently being
      associated with lower obesity values (P-value <0.001-0.05). The adiponectin
      polymorphisms, in particular those in the promoter region, thus show significant
      association with obesity measures in the Hispanic population. Additional studies
      are needed to confirm our findings and determine which polymorphism causes the
      functional effect.

PMID- 15843990
TI  - ATM haplotypes and associated mutations in Iranian patients with ataxia
      telangiectasia: recurring homozygosity without a founder haplotype.
AB  - Ataxia-telangiectasia (A-T) is an autosomal recessive disorder caused by
      mutations in the ATM gene. The ATM gene spans more than 150 kb at chromosomal
      region 11q23.1 and encodes a product of 3,056 amino acids. The ATM protein is a
      serine/threonine protein kinase and is involved in oxidative stress, cell cycle
      control, and DNA repair. We analyzed the 11q22-23 haplotypes and associated
      mutations of 16 Iranian families. We utilized standardized short tandem repeat
      (STR) haplotypes to enhance mutation identification. In addition to the STR
      markers, single-nucleotide polymorphism haplotypes were determined, using three
      critical polymorphisms. The entire gene was screened sequentially by protein
      truncation testing, single-strand conformation polymorphism, and denaturing high
      performance liquid chromatography to identify the disease-causing mutations. Of
      the expected 32 mutations, 25 (78%) were identified. All but two mutations led to
      a truncated or null form of the ATM protein (nonsense, splice site, or
      frameshift). Twelve mutations were identified for 15 haplotypes. Five mutations
      were novel. Mutations were located throughout the entire gene, with no
      clustering. Despite the absence of an Iranian founder mutation, three-fourths of
      the families were homozygous, suggesting that many undetected ATM mutations still
      exist in Iran. This study establishes a database for Iranian A-T families, and
      extends the global spectrum of ATM mutations.

PMID- 15843991
TI  - Domain near TM1 influences agonist and antagonist responses of peptide-gated Na+
      channels.
AB  - A molecular biological approach was used to analyse the importance of different
      amino acids for ligand activation and for determining the action of amiloride on
      peptide- (Phe-Met-Arg-Phe-NH(2), FMRFamide)-gated Na(+) channels, members of the
      degenerin/epithelial Na channel (DEG/ENaC) family. Amiloride is a low-affinity
      blocker of most DEG/ENa channels, but has an unusual enhancing effect on
      responses of some of them. Chimeras were expressed in Xenopus oocytes and studied
      electrophysiologically. Differences in properties of channels from Helix aspersa
      and Helisoma trivolvis highlighted a sequence of 50 residues of the extracellular
      domain, near the first transmembrane segment (TM1), that affected sensitivity to
      FMRFamide, and whether amiloride blocked or enhanced the response to FMRFamide.
      Comparisons of chimeras prepared from H. aspersa and the extracellular domains of
      two other species, Aplysia californica and Lymnaea stagnalis and the preparation
      of further constructs, showed that amino acids 128-134 in the H. aspersa sequence
      are important in determining the predominant effect of amiloride and influencing
      the EC(50) of FMRFamide. The results also showed that amino acids in this region
      are influenced by amino acids in other regions of the extracellular domain so as
      to affect not only the magnitude of responses, but also their time course and
      desensitisation.

PMID- 15843992
TI  - [Combination treatment with antisense oligonucleotides and chemotherapy in
      vitro].
AB  - Oncological therapy strategies are increasingly concentrating on the causal,
      molecular changes involved in carcinogenesis. So called "smart drugs" such as
      antisense oligoneucleotide (AsON) can be used as specific inhibitors of
      individual genes. AsONs have shown their effectiveness in many studies. Clinical
      studies have demonstrated, however, that for many tumours the inhibition of a
      single gene is, due to multigenetic alteration, largely ineffective. The
      combination of AsONs with conventional chemotherapeutic agents is currently being
      investigated in phase III studies. In these studies, chemotherapeutic agents have
      been evaluated in cell culture together with AsON against the proliferation
      associated Ki-67 gene, as well as against the apoptosis associated bcl-2 gene via
      RT-PCR, immunochemistry and MTT cell viability assay. For both AsONs, significant
      target inhibition was achieved in cell culture with a high target gene
      expression. The prior treatment of tumour cells with bcl-2 AsON significantly
      increased the effectiveness of chemotherapy, while the combination of
      conventional chemotherapeutic agents with Ki-67 AsON showed no synergistic
      effects.

PMID- 15843993
TI  - Y-STR typing of an Austrian population sample using a 17-loci multiplex PCR
      assay.
AB  - Y-chromosomal STR haplotypes were determined from a sample of 135 unrelated men
      and 70 sons from Tirol (Austria) using the AmpFlSTR Yfiler PCR amplification kit
      (Applied Biosystems) that coamplifies 17 Y-STRs. The panel of markers includes
      the 9-loci European minimal haplotype (minHt) and, in addition, the markers
      DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 (Y GATA C4) and Y GATA H4.
      A total of 130 different haplotypes (125 were unique) were identified by the 17 Y
      STR markers, an increase of 19 compared with the minHt. The gene diversity of
      DYS635, DYS456 and DYS458 exceeded 0.75 and only that of the duplicated marker
      DYS385 (0.86) was higher. Consistently high haplotype diversity values were found
      in all tested Y-SNP haplogroups. Because the simultaneous analysis of 17 Y-STR
      systems offers a high power of discrimination at minimum sample consumption, the
      Yfiler kit is a promising tool for forensic applications.

PMID- 15843994
TI  - Forensic analysis of the mitochondrial coding region and association to disease.

PMID- 15843995
TI  - A Monte Carlo-based model for steady-state diffuse reflectance spectrometry in
      human skin: estimation of carbon monoxide concentration in livor mortis.
AB  - In terms of physics, the skin can be regarded as an optically turbid medium in
      which the light is mainly scattered by the collagen fibers, mitochondria and cell
      nuclei, whereas the absorption is determined by the content of reduced
      hemoglobin, oxyhemoglobin, bilirubin, and melanin. When the measuring geometry
      and the illumination spectrum are known, the optical characteristics of the skin
      can be approximately described by the diffusion and absorption coefficients.
      These values define the diffusion and absorption probability per unit distance
      traveled for each wavelength. Based on these parameters, a mathematical skin
      model was developed with the help of Monte Carlo simulations. By implementing the
      absorption coefficient of carbon monoxide hemoglobin (CO-Hb) into the skin model,
      the authors wanted to investigate whether this method is suitable to determine
      the CO-Hb concentration from spectral reflectance curves of livores. The
      investigations performed on 28 deaths from CO poisoning so far showed that this
      is generally possible. In almost all cases, the actual CO-Hb values could be
      estimated correctly by using the Monte Carlo simulations.

PMID- 15843996
TI  - Clinical, sociodemographic, and local system factors associated with a hospital
      death among cancer patients.
AB  - OBJECTIVE: The study was conducted to examine factors associated with hospital
      deaths among a group of cancer patients. PATIENTS AND METHODS: A retrospective
      chart review of the M. D. Anderson Cancer Center Tumor Registry was conducted.
      Participants were all adult cancer patients, residents of the State of Texas
      diagnosed and treated since January 1, 1990, and who died during the years 1999
      and 2000. The study outcome was the site of death. MAIN RESULTS: The inclusion
      criteria were met by 866 patients of whom 504 (58%) died in a hospital. The group
      included 489 (56%) men. A number of 641 (74%) were White, 104 (12%) Hispanic, 92
      (11%) Black, and 29 (3%) of other origin. The majority, 501 (58%), had been
      diagnosed with stage IV disease, and the median survival time was 14 months.
      Multivariate logistic regression analysis showed patients diagnosed with
      hematologic cancers to be significantly more likely (p<0.001) of dying in
      hospitals, odds ratio [OR 2.88] and confidence interval [95% CI 1.79-4.63], women
      diagnosed with breast and gynecological cancers were significantly less likely
      (p=0.03) of dying at hospitals odds ratio [OR 0.64] and confidence interval [95%
      CI 0.42-0.96], when compared with patients diagnosed with other cancers. Lower
      household income per zip code of residency was marginally associated (p=0.06)
      with hospital deaths. CONCLUSIONS: The study identified groups of cancer patients
      at risk of hospital death. These results should account when planning the
      allocation of hospital palliative care services as well as when informing policy
      decisions about health care financing and delivery of these services.

PMID- 15843998
TI  - Blood pressure and total peripheral resistance in children with chronic kidney
      disease.
AB  - We performed a study to assess cardiac output (CO) and total peripheral
      resistance (TPR) at rest and during peak exercise with the goal to better define
      the role of these parameters in the development of hypertension in children with
      chronic kidney disease (CKD) stage 2-4. Fifty-two pediatric patients with CKD
      (mean age 12.7+/-3.7 years) and 28 healthy individuals of comparable age and sex
      participated in the study. At rest, children with CKD had a significantly higher
      systolic and diastolic blood pressure (BP) and calculated mean arterial pressure
      (MAP) than healthy controls. Total peripheral resistance was significantly higher
      in children with CKD than in controls (1627.7+/-534.6 vs 1354.6+/-338.9
      dynexsxcm(-5), p =0.02). There was no significant difference in heart rate or CO
      between the two groups. Children taking antihypertensive medications had lower
      TPR than children without BP medications (1514.6+/-439.6 vs 1788.2+/-505.4
      dynexsxcm(-5), respectively, p =0.06). At peak exercise, children with CKD had a
      significant increase in MAP, heart rate and CO and had a significant decrease in
      TPR (difference between rest and peak exercise: -782.4+/-375.9 dynexsxcm(-5), p
      <0.001). Children taking BP medications had blunted MAP and CO responses when
      compared to controls (Delta CO: 6.2+/-2.8 l/min vs 9.8+/-4.5 l/min, respectively,
      p =0.01; MAP: 13.9+/-10.2 mmHg vs 21.5+/-11.7 mmHg, respectively, p =0.01).
      Children without BP medications had a similar to controls response to exercise in
      respect to CO, MAP and TPR. We conclude that increased TPR is a major contributor
      to elevated blood pressure in children with CKD and suggest that BP medications
      decreasing vascular resistance should be used as a first line of antihypertensive
      therapy in these patients.

PMID- 15843997
TI  - Efficacy of AIDS vaccine strategies in nonhuman primates.
AB  - Since only a limited number of vaccines can be tested for efficacy in phase 3
      studies in humans, a filter is needed allowing selection of the most promising
      ones. Although differences between HIV infection in humans and simian
      immunodeficiency virus infection in nonhuman primates (NHP) might limit the
      predictive value of these models, comparative efficacy studies in NHPs could
      facilitate ranking of vaccine candidates. While various forms of protein vaccines
      failed to induce consistent protection, live-attenuated vaccines, DNA vaccines
      and viral vector vaccines provided various levels of protection in NHPs. However,
      variability in the experimental models limits the conclusions that can be drawn
      with respect to the relative efficacy of vaccines not tested in the same
      experiment. Therefore, better standardization is an urgent necessity in order to
      exploit the full potential of nonhuman primate models in AIDS vaccine
      development.

PMID- 15843999
TI  - Recombinant tissue plasminogen activator infusion for hemodialysis catheter
      clearance.
AB  - Hemodialysis (HD) catheter occlusion is a common cause of poor blood flow and
      inadequate dialysis. In order to address this problem in our pediatric dialysis
      unit, we elected to use short (2-h) infusions of low-dose recombinant tissue
      plasminogen activator (rtPA) for thrombolysis of occluded catheters. Catheters
      meeting diagnostic criteria for thrombosis were infused with 2.5 mg rtPA in 25 ml
      0.9 normal saline over 2 h prior to dialysis. Retrospective data collection was
      carried out to assess the success of this procedure. Variables assessed included
      blood flow (Qb), transmembrane pressure (TMP) and venous pressure (VP) before and
      after rtPA infusion. Seven catheter thromboses in six patients were successfully
      treated with rtPA; there were significant improvements in Qb ( p <0.01), TMP ( p
      <0.01), and VP ( p <0.02). At 32 weeks after rtPA therapy, Kaplan-Meier survival
      analysis showed a 60% probability of primary catheter patency. At the end of the
      study, 85% of catheters had adequate function as defined by a Qb >200 ml/min. No
      adverse events were observed. Low-dose rtPA infusion is safe and effective for
      catheter thrombolysis in outpatient pediatric HD patients. It may serve as an
      alternative method of administration to local instillation and may be used to
      restore patency before resorting to surgical revisions.

PMID- 15844000
TI  - Triamcinolone acetonide: a new management of noncompliance in nephrotic children.
AB  - Noncompliance is frequent in children and adolescents with nephrotic syndrome.
      Once suspected, noncompliance is difficult to confirm and often impossible to
      avoid. The standard oral glucocorticoid treatment for children has been shown to
      be efficient and safe. However, a small number of children/parents are
      noncompliant to the steroid treatment, resulting in multiple relapses. For these
      patients the use of steroids with prolonged half-life such as triamcinolone
      acetonide (TA) can be helpful. We studied seven children (six boys, one girl;
      median age at diagnosis 8.6 years, range 1.8-10.7) receiving conventional steroid
      treatment for a median of 30 months (8-74) before starting intramuscular (IM) TA
      treatment. The standard prednisone treatment was replaced by 1 monthly IM
      injection of TA (1 mg/kg per day oral prednisone replaced by 1 mg/kg per month IM
      TA). The treatment was tapered off by a reduction of 10-20% of the initial dose
      per month over 6-8 months. After a mean observation period of 14 months (3-36)
      the results were evaluated in terms of number of relapses and treatment
      tolerance. Four children showed a clear decrease in number of relapses (1.8 to 0
      per year); in the other three the number of relapses remained stable. Tolerance
      was excellent (no cataract, no arterial hypertension), and the cushingoid
      syndrome did not exceed the level experienced under conventional oral steroid
      therapy. However, growth velocity decreased during the TA treatment and returned
      to normal after discontinuation of TA. These preliminary results demonstrate that
      TA may be used in patients of suspected noncompliance in steroid-sensitive
      patients who respond with a complete remission during TA treatment over the
      observation period. Patients who do not benefit from the TA can be classified as
      very probably steroid-dependent. TA seems to be a useful therapeutic strategy in
      those patients for whom noncompliance is strongly suspected.

PMID- 15844001
TI  - Clinico-pathologic findings in medullary cystic kidney disease type 2.
AB  - Medullary cystic kidney disease type 2 is an uncommon autosomal dominant
      condition characterized by juvenile onset hyperuricemia, precocious gout and
      chronic renal failure progressing to end-stage renal disease in the 4th through
      7th decades of life. A family suffering from this condition is described. The
      patient in the index case presented with renal insufficiency as a child. A renal
      biopsy revealed tubular atrophy, and immunohistochemical staining of the tissue
      for uromodulin (Tamm Horsfall protein) revealed dense deposits in renal tubular
      cells. Genetic testing revealed a single nucleotide mutation (c.899G>A) resulting
      in an exchange of a cysteine residue for tyrosine (C300Y). Medullary cystic
      kidney disease type 2 (also known as uromodulin-associated kidney disease) likely
      represents a form of endoplasmic reticulum storage disease, with deposition of
      the abnormal uromodulin protein in the endoplasmic reticulum, leading to tubular
      cell atrophy and death.

PMID- 15844002
TI  - Magnolol induces the distributional changes of p160 and adipose differentiation
      related protein in adrenal cells.
AB  - Magnolol stimulates adrenal steroidogenesis and induces the distributional
      changes of p160 and adipose differentiation-related protein (ADRP) in rat adrenal
      cells. This study investigated the underlying signaling mechanisms involved in
      these processes. Magnolol (30 microM) caused a time-dependent increase in the
      phosphorylation of extracellular signal-related kinase (ERK) in cultured adrenal
      cells. The following evidence supports a link between ERK activation and p160
      translocation. First, the magnolol-induced redistribution of p160 from the lipid
      droplet surface to the cytosol, resulting in the decrease in the percentages of
      p160-positive cells, and this decrease in p160-positive cells was completely
      blocked by pretreatment with either of the MAPK-ERK kinase (MEK) inhibitors
      PD98059 or U0126. Second, magnolol did not significantly decrease total p160
      protein levels but caused an increase in threonine phosphorylation of p160, which
      reached a maximum after 5 min of magnolol treatment, and this magnolol-induced
      phosphorylation of p160 was prevented by pretreatment with U0126, suggesting the
      involvement of ERK. In addition, magnolol decreased both ADRP immunostaining
      intensity at the lipid droplet surface and the percentage of ADRP-positive cells.
      This was further confirmed biochemically by the decrease in ADRP levels in total
      cell homogenates and in lipid droplet fractions. Magnolol-induced decrease in
      ADRP staining at the lipid droplet surface was not affected by pretreatment with
      PD98059 or U0126, indicating that ERK signaling was not involved in this event.
      Furthermore, treatment with 30 microM magnolol for 6 h resulted in about 50%
      decrease in ADRP protein level. Therefore, decreased protein levels of p160 and
      ADRP at the lipid droplet surface induced by magnolol were mediated via two
      different mechanisms: phosphorylation of p160 and downregulation of ADRP
      expression, respectively.

PMID- 15844003
TI  - Expression and immunolocalization of water-channel aquaporins in the rat and
      mouse mammary gland.
AB  - We examined the expression and immunolocalization of water-channel aquaporins in
      the mammary gland by reverse transcriptase polymerase chain reaction (RT-PCR),
      immunoblotting, and immunohistochemistry. RT-PCR and immunoblotting revealed the
      expression of aquaporin-1 (AQP1) and AQP3 in the lactating rat mammary gland.
      AQP3 was detected in the alveolar epithelium and duct system whereas AQP1 was
      found in the capillaries and venules. AQP3 was present in the basolateral
      membrane of secretory epithelial cells and intralobular and interlobular duct
      epithelial cells. The main duct near the orifice in the nipple, which is
      comprised of a stratified epithelium, bore AQP3 in its basal and intermediate
      layers. AQP1 was located in both the apical and basolateral membranes of
      capillary and venule endothelia. AQP3 was not detected in virgin females. AQP3
      was found in some differentiating mammary epithelial cells in the pregnant rat.
      AQP1 was present in capillaries and venules in the differentiating mammary gland
      of the pregnant rat and in the mammary fat pad of virgin females. We found a
      similar distribution of AQP1 and AQP3 in the mouse. AQP1 and AQP3 seem to play
      roles in the synthesis and/or secretion of milk.

PMID- 15844004
TI  - Upregulation of receptor activator of nuclear factor-kappaB ligand expression in
      the thymic subcapsular, paraseptal, perivascular, and medullary epithelial cells
      during thymus regeneration.
AB  - The receptor activator of nuclear factor (NF)-kappaB ligand (RANKL; also termed
      TRANCE/OPGL/ODF/TNFSF11), a new member of the tumor-necrosis factor (TNF)
      superfamily, was identified as a key cytokine involved in the differentiation of
      the immune system and the regulation of immunity as well as in bone metabolism.
      In particular, RANKL-deficient mice showed defects in the early differentiation
      of T lymphocytes, suggesting that RANKL is a novel regulator of early thymocyte
      development. Here, we describe the expression of RANKL during regeneration
      following acute involution induced by cyclophosphamide in the rat thymus. The
      present study demonstrates the presence and upregulated expression of the RANKL
      in thymic subcapsular, paraseptal, perivascular, and medullary epithelial cells
      during thymus regeneration. Our results suggest that the RANKL expressed in these
      thymic epithelial cells plays a role in the development of T cells during thymic
      regeneration.

PMID- 15844005
TI  - Organization of visuo-spatial serial memory: interaction of temporal order with
      spatial and temporal grouping.
AB  - This study investigates whether memory for sequences of spatial locations can be
      represented hierarchically, that is, as successive groups containing the order of
      constituent locations. Two grouping manipulations are used: Temporal grouping,
      based on the verbal serial memory literature, and spatial grouping, based on
      recent empirical work on visuo-spatial serial memory. In Experiment 1, we examine
      the relationship between spatial grouping and temporal order and showed that
      recall performance increases when both temporal and spatial organization
      correlate, but decreases when they clash. Experiments 2 and 3 show that the
      latter result is confounded by differences in path length (length of spatial path
      defined by the locations) between conditions, and that no effect of the spatial
      organization is observed when path length is controlled for. In Experiment 4, an
      alternative method to spatial grouping, temporal grouping, is used to induce
      hierarchical organization. A recall advantage is found in the temporal grouping
      condition. The results suggest that hierarchical representations can be imposed
      on order information for visuo-spatial sequences, either when participants have
      pre-existing knowledge about the form of the path formed by the sequence or when
      temporal boundaries delimit chunks; that increased path length is the cause of
      the performance decrement observed when dots from separate spatial groups are
      presented successively; and that path length and more generally sequence
      characteristics should be taken into account in designing future research on
      visuo-spatial serial memory.

PMID- 15844006
TI  - The influence of intentional and incidental learning on acquiring spatial
      knowledge during navigation.
AB  - In order to study the influence of intentional and incidental learning conditions
      on route learning, young adults walked a route through a university building.
      Half of the participants focused their attention on the route (intentional
      learning condition), while the other half did not (incidental learning
      condition). Five tests of spatial knowledge were employed: a route-length
      estimation, landmark recognition, landmark ordering, map-drawing and navigation
      task. The intentional group performed better than the incidental group on the map
      drawing and navigation task. No difference between the intentional and incidental
      group was found on the landmark-recognition and landmark-ordering task. Moreover,
      the intentional group overestimated the walking distance, while the incidental
      group underestimated it. These results suggest that route knowledge (landmark
      recognition and landmark ordering) requires less effortful processing than survey
      knowledge (developing a map-like representation and actual navigation).

PMID- 15844007
TI  - Pharmacokinetic and pharmacodynamic comparison of fluoropyrimidine derivatives,
      capecitabine and 5'-deoxy-5-fluorouridine (5'-DFUR).
AB  - PURPOSE: Capecitabine is a three-step prodrug that was rationally designed to be
      a more effective and safer alternative to its intermediate metabolite, 5'-deoxy-5
      fluorouridine (5'-DFUR). We compared the pharmacokinetics/pharmacodynamics of
      these drugs in metastatic breast cancer patients. METHODS: Six patients received
      oral capecitabine at 1657 mg/m2 twice daily and 17 received 5'-DFUR at 400 mg
      three times daily. Both drugs were administered for 21 days followed by a 7-day
      rest. RESULTS: Median daily 5'-DFUR AUC was significantly higher for capecitabine
      than for 5'-DFUR (81.1 vs 32.6 mmol h/l; P = 0.01). Following treatment with 5'
      DFUR, the median AUC and Cmax of 5'-DFUR tended to be higher in patients with a
      partial response (3.83 microg h/ml and 4.88 microg/ml) and stable disease (6.46
      microg h/ml and 4.96 microg/ml) than in those with disease progression (2.53
      microg h/ml and 1.36 microg/ml). The AUC and Cmax of 5'-DFUR was significantly
      related to overall survival. CONCLUSIONS: These results support the superiority
      of capecitabine over 5'-DFUR.

PMID- 15844008
TI  - [New instruments for tonsillectomy].

PMID- 15844009
TI  - Risedronate in the treatment of Murine Chagas' disease.
AB  - Risedronate, a bisphosphonate, was used to treat CD-1 mice infected with the
      Brazil strain of Trypanosoma cruzi. When given by subcutaneous injection 3
      times/week, there was a significant reduction in mortality, however, the
      myocardial pathology and right ventricular dilation was unchanged in these mice
      compared to control animals. In C57BL/6 mice infected with the Tulahuen strain,
      there was no change in mortality in response to risedronate treatment. These data
      suggest that this class of compounds has activity against T. cruzi in vivo and
      illustrate the utility of imaging and pathologic studies as adjuncts in the
      evaluation of therapeutic compounds as treatments for experimental Chagas'
      disease. In addition, it underscores the need to use different strains of T.
      cruzi.

PMID- 15844010
TI  - Acute effects of self-paced walking on urges to smoke during temporary smoking
      abstinence.
AB  - RATIONALE: Recent research highlights the need to extend our understanding of how
      exercise may aid smoking cessation, through exploration of different modes,
      intensity and duration of exercise. OBJECTIVES: The purpose of the study was to
      examine the effects of a 1-mile self-paced walk on different measures of urges to
      smoke following temporary smoking abstinence. METHODS: In a within-subject
      counterbalanced design, following 15 h of smoking abstinence, participants (N=15)
      exercised or sat passively on separate days. A single-item measure of strength of
      desire to smoke was administered during, immediately post, and at 10 and 20 min
      post-treatment. The two-factor Questionnaire for Smoking Urges, involving
      intention and desire to engage in smoking behaviour which is anticipated as
      pleasant, enjoyable and satisfying (desire-behave), and anticipation of relief
      from negative affect through smoking (desire-affect relief), was administered
      before and 20 min post-treatment. RESULTS: A two-way repeated-measures MANOVA
      revealed a significant overall interaction effect for time by condition for
      strength of desire to smoke, and the two QSU scales. Two-way repeated-measures
      univariate ANOVAs revealed significant interaction effects for time by condition
      for each of the three urges to smoke measures. Planned contrasts revealed that
      exercise reduced cigarette cravings for up to 20 min after exercise, in
      comparison with the control condition. ANCOVAs revealed mixed support for
      independent effects of exercise on all measures of urges to smoke. CONCLUSION: A
      self-paced walk, at a low intensity, lasting 15-20 min can have a rapid and
      measurable positive effect on both single and multi-item measures of urges to
      smoke, lasting at least 20 min, during temporary smoking abstinence.

PMID- 15844011
TI  - Identification of a novel mutation in the DSRAD gene in a Chinese pedigree with
      dyschromatosis symmetrica hereditaria.
AB  - Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant skin
      disorder characterized by a mixture of hyperpigmented and hypopigmented macules
      distributed on the face and dorsal aspects of the extremities that appear in
      infancy or early childhood. The DSH locus has recently been mapped to chromosome
      1q21 and then pathogenic mutations have been identified in the DSRAD gene. In the
      study reported here we examined the DSRAD gene mutations of a three-generation
      Chinese pedigree with DSH by direct sequencing. We identified a novel
      heterozygous nucleotide T-->C transition at position 3388 in exon 14 of the DSRAD
      gene which induces a C1130R change in the putative deaminase domain of DSRAD. Our
      study expands the database on the DSRAD gene mutations in DSH and enriches the
      knowledge about the function of the DSRAD gene.

PMID- 15844012
TI  - Gene cloning, expression and partial characterization of cell division protein
      FtsZ1 from extremely halophilic archaeon Haloarcula japonica strain TR-1.
AB  - The gene encoding a cell division protein FtsZ1 was cloned from an extremely
      halophilic archaeon, Haloarcula japonica strain TR-1. Nucleotide sequencing
      analysis of the ftsZ1 gene revealed that the structural gene consisted of an open
      reading frame of 1,158 nucleotides encoding 386 amino acids. Transcription of the
      ftsZ1 gene in Ha. japonica was confirmed by RT-PCR. A modified ftsZ1 gene was
      inserted into the shuttle vector pWL102 and used to transform Ha. japonica. The
      recombinant FtsZ1 was produced as a fusion with hexahistidine-tag in Ha. japonica
      host cells and purified. Purified recombinant FtsZ1 exhibited GTP-dependent
      polymerization activity and GTP-hydrolyzing activity in the presence of high
      concentrations of KCl.

PMID- 15844013
TI  - Pressure-regulated biosynthesis of cytochrome bd in piezo- and psychrophilic deep
      sea bacterium Shewanella violacea DSS12.
AB  - The genes of cytochrome bd-encoding cydAB were identified from a deep-sea
      bacterium Shewanella violacea DSS12. These showed significant homologies with
      known cydAB gene sequences from various organisms. Additionally, highly conserved
      regions that are important for the enzymatic function were also conserved in cydA
      of S. violacea. Based on the results, transcriptional analysis of cydAB operon
      and cydDC operon (required for assembly of cytochrome bd) of S. violacea in
      microaerobic condition was performed under the growth condition of various
      pressures. The gene of cydA was expressed even under the condition of atmospheric
      pressure and its expression was enhanced with pressurization. On the other hand,
      the expression of cydC was strongly depressed under the condition of atmospheric
      pressure compared with the case under high pressure. It appeared
      spectrophotometrically that loss of cytochrome bd in S. violacea under
      atmospheric pressure shown in previous study is caused mainly by the loss of
      cydDC. Further, under the growth condition of atmospheric pressure, either less
      amount or no d-type cytochrome was expressed compared with the case of high
      pressure condition even if the organism was grown under alkaline condition or in
      the presence of uncoupler, which are the inducible condition of d-type cytochrome
      in Escherichia coli. These results suggested that the significant amount of d
      type cytochrome expression is specific event under the growth condition of high
      pressure.

PMID- 15844014
TI  - Novel psychrophilic anaerobic spore-forming bacterium from the overcooled water
      brine in permafrost: description Clostridium algoriphilum sp. nov.
AB  - A gram-positive, motile, strict anaerobic spore-forming bacterium was isolated
      from the over-cooled brine in the permafrost. The optimal temperature for isolate
      growth was 5-6 degrees C at pH 6.8-7.2. The bacterium was growing on the medium
      rich in saccharides and disaccharides. Out of polysaccharides tested, only xylan
      sustained the growth. Fermentation of the hexoses led to the formation of
      acetate, butyrate, lactate, H2,CO2 and some formate and ethanol. Cell wall
      peptidoglycan contained meso-diaminopimelic acid. The major fatty acids of the
      cell wall were C(14:0) and C(16:1c9). The content of G-C pairs in DNA was 31.4
      mol%. As phylogenetic analysis has shown, it is closely linked to the members of
      cluster 1 of Clostridium. It differs from the other species of the genus by the
      substrates necessary for the growth, products forming as a result of the
      fermentation and content of the fatty acids in the cell wall. Thus, it was
      suggested to describe this strain as a new species named Clostridium
      algoriphilum. Type strain 14D1 was deposited into the Russian Collection of the
      Microorganisms VKM B-2271T and German Collection of the Microorganisms DSM 16153T
      .

PMID- 15844017
TI  - Transoral obesity surgery: endoluminal gastroplasty with an endoscopic suture
      device.
AB  - BACKGROUND AND STUDY AIMS: Surgical creation of a small gastric pouch with a
      restricted outlet is a well-established option for the treatment of morbid
      obesity. This report describes initial experience with endoscopic transoral
      stomach partition using a newly designed suturing apparatus. MATERIALS AND
      METHODS: A fresh porcine stomach was placed in the Erlangen model. A prototype
      suture device, incorporating a curved needle and an intracorporeal tightening
      mechanism, was used in this procedure. A long fishing line was first introduced
      into the stomach, with the two ends left outside. The suturing device, premounted
      outside a standard gastroscope, was inserted into the stomach and delivered
      several stitches attaching the fishing line to both the anterior and posterior
      walls along the line for the stomach to be partitioned. Five throws of half
      hitches were tied onto the fishing line extracorporeally and separately pushed
      into place, creating a gastric pouch just below the esophagogastric junction. A
      flexible sheath of 8 cm long was then put on one side of the fishing line and
      pushed into the stomach. Additional extracorporeal knots were tied on the fishing
      line, forming a restrictive ring at the outlet of the pouch. The ring was then
      anchored to the stomach wall with similar endosutures. RESULTS: The proximal
      gastric pouch, with an estimated volume of approximately 100 ml, was successfully
      created with a restrictive band at its outlet. All of the stitches were securely
      sutured, with consistent penetration of the muscular layer of the stomach wall.
      CONCLUSIONS: In a bench model, it is technically possible to accomplish transoral
      gastroplasty endoscopically with an intraluminal suturing device. Further live
      animal studies will be needed in order to confirm the efficacy and safety of this
      procedure before clinical application.

PMID- 15844015
TI  - Physiological responses of the halophilic archaeon Halobacterium sp. strain NRC1
      to desiccation and gamma irradiation.
AB  - We report that the halophilic archaeon Halobacterium sp. strain NRC-1 is highly
      resistant to desiccation, high vacuum and 60Co gamma irradiation. Halobacterium
      sp. was able to repair extensive double strand DNA breaks (DSBs) in its genomic
      DNA, produced both by desiccation and by gamma irradiation, within hours of
      damage induction. We propose that resistance to high vacuum and 60Co gamma
      irradiation is a consequence of its adaptation to desiccating conditions. Gamma
      resistance in Halobacterium sp. was dependent on growth stage with cultures in
      earlier stages exhibiting higher resistance. Membrane pigments, specifically
      bacterioruberin, offered protection against cellular damages induced by high
      doses (5 kGy) of gamma irradiation. High-salt conditions were found to create a
      protective environment against gamma irradiation in vivo by comparing the amount
      of DSBs induced by ionizing radiation in the chromosomal DNA of Halobacterium sp.
      to that of the more radiation-sensitive Escherichia coli that grows in lower-salt
      conditions. No inducible response was observed after exposing Halobacterium sp.
      to a nonlethal dose (0.5 kGy) of gamma ray and subsequently exposing the cells to
      either a high dose (5 kGy) of gamma ray or desiccating conditions. We find that
      the hypersaline environment in which Halobacterium sp. flourishes is a
      fundamental factor for its resistance to desiccation, damaging radiation and high
      vacuum.

PMID- 15844018
TI  - Assessing the adequacy of endoscopically tied knots: a functional approach.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic intracorporeal knots have potentially
      enormous applications in endoscopic surgery. We describe a method for testing the
      security of various types of endoscopically tied knots using a vessel perfusion
      manometer system. METHODS: A 4-cm segment of porcine splenic artery was placed on
      the mucosal surface of a pig stomach. The two ends of the vessel were brought out
      through the gastric wall and connected to a two-way manometer. One end was also
      joined to a pressure infusion bag. The stomach was mounted in an Erlangen
      training model. A long 3/0 nylon thread, previously introduced into the
      submucosal layer of the stomach and encircling the vessel, was brought out from
      the mouth. Three-throw square knots, Mayo knots, "surgeon's" knots and five-throw
      square knots were tied and pushed into place using a cap attached to a
      gastroscope. The pressure at the two ends of the artery was compared. If the
      pressure could be increased to over 200 mm Hg at one end without a change in the
      other, the knot was considered secure. RESULTS: Each type of knot was tested 12
      times under endoscopic vision. The range for mean knotting time was 3.4 - 4.5
      minutes. Five-throw knots took significantly longer to tie than three-throw knots
      (P < 0.005). There was one loose knot in each of the three-throw and Mayo groups,
      and three each in the "surgeon's" and five-throw groups (P > 0.05). CONCLUSIONS:
      This system is a reliable model for testing intracorporeal knots tied
      endoscopically. A three-half-hitches square knot with 3/0 nylon, tied using a
      flexible endoscope and knot-tightening cap, can withstand pressure up to 200 mm
      Hg.

PMID- 15844019
TI  - Poor results of 5-aminolevulinic acid-photodynamic therapy for residual high
      grade dysplasia and early cancer in barrett esophagus after endoscopic resection.
AB  - BACKGROUND AND STUDY AIMS: The aim of the study was to evaluate the efficacy of
      photodynamic therapy (PDT) in the treatment of residual high-grade dysplasia or
      early cancer (HGD/EC) after endoscopic resection in Barrett esophagus. PATIENTS
      AND METHODS: Study patients were separated into group A, with proven residual
      HGD/EC, and group B with possible HGD/EC (positive lateral margins in the
      endoscopic resection specimen, without HGD/EC in the remaining Barrett
      esophagus). PDT treatment consisted of 5-aminolevulinic (5-ALA)
      photosensitization (40 mg/kg) followed by illumination of the Barrett esophagus
      with a total light dose of 100 J/cm (2). Complete remission was defined as the
      absence of HGD/EC in biopsies taken in two consecutive follow-up endoscopies. The
      percentage regression of Barrett esophagus, as well as the recurrence rate of
      HGD/EC, was calculated. RESULTS: 20 patients underwent PDT (group A, 11; group B,
      9). Mild complications were seen in 4/26 procedures. The overall success rate was
      15/20 (75 %). There was a significant difference in success rate between group A
      (55 %) and group B (100 %); P = 0.03. All patients had residual Barrett esophagus
      after PDT; the median regression percentage was 50 % (IQR 25 - 70 %). Recurrence
      of HGD/EC occurred in four patients (two each in groups A and B) after a median
      follow up of 30 months. CONCLUSIONS: In this selected group of patients, the
      addition of 5-ALA-PDT after endoscopic resection for HGD/EC had a disappointing
      success rate in patients who had residual HGD/EC after endoscopic resection. Most
      patients undergoing 5-ALA-PDT have residual Barrett mucosa after PDT and 5-ALA
      PDT does not seem to prevent recurrences during follow-up.

PMID- 15844020
TI  - Prospective study of the effectiveness of percutaneous transhepatic photodynamic
      therapy for advanced bile duct cancer and the role of intraductal ultrasonography
      in response assessment.
AB  - BACKGROUND AND STUDY AIMS: We evaluated the therapeutic effects of percutaneous
      transhepatic photodynamic therapy (PDT) in patients with advanced bile duct
      cancer. The utility of intraductal ultrasonography (IDUS) for the assessment of
      responses and for regular follow up after PDT was also examined. METHODS:
      Percutaneous transhepatic biliary drainage (PTBD) was initiated before PDT.
      Following dilation and maturation of the PTBD tract, percutaneous PDT was
      performed. Intraluminal photoactivation was carried out using percutaneous
      cholangioscopy 2 days after intravenous application of a hematoporphyrin
      derivative. All patients were additionally provided with percutaneous bile duct
      drainage catheters after PDT. IDUS was conducted monthly to measure the thickness
      of the tumor mass before and after PDT. RESULTS: 24 patients with advanced
      cholangiocarcinomas (Bismuth IIIa, n = 4; IIIb, n = 10; IV, n = 10) were treated
      with PDT. At 3 months after PDT, the mean thickness of the tumor mass had
      decreased from 8.7 +/- 3.7 mm to 5.8 +/- 2.0 mm (P < 0.01). At 4 months after
      PDT, the thickness of the mass had increased to 7.0 +/- 3.7 mm. Quality of life
      indices improved dramatically and remained stable 1 month after PDT; the
      Karnofsky index increased from 39.1 +/- 11.36 to 58.2 +/- 22.72 points (P =
      0.003). The 30-day mortality rate was 0 %, and the median survival time was 558
      +/- 178.8 days (current range 62 - 810 days). CONCLUSIONS: PDT using percutaneous
      cholangioscopy is safe and effective for advanced hilar cholangiocarcinoma, and
      seems to prolong survival. IDUS is useful for evaluating changes in the thickness
      of the tumor mass after PDT.

PMID- 15844021
TI  - Endoscopic argon plasma trimming of biliary and gastrointestinal metallic stents.
AB  - BACKGROUND AND STUDY AIMS: The aim of this study was to assess the feasibility
      and efficiency of plasma argon trimming of gastrointestinal and biliary metallic
      stents. PATIENTS AND METHODS: A total of 31 patients underwent plasma argon
      trimming of their metallic stents (14 women, 17 men; mean +/- SD age 73 +/- 12.2
      years, range 46 - 96 years). Of these 31 patients, 24 had had covered or
      noncovered Unistep Wallstents placed in the biliary tract (13 patients with
      pancreatic neoplasms, five patients with Vater ampulloma, five patients with
      biliary tract carcinoma and one patient with chronic calcifiying pancreatitis);
      three patients had noncovered Enteral Unistep Wallstents (pyloroduodenal); two
      patients with obstructive colorectal carcinoma had a noncovered Bard Memotherm
      stent inserted; and two patients had noncovered Ultraflex stents placed for
      esophageal carcinoma. Endoscopic trimming of the stents was performed under
      propofol-induced general anesthesia, with the power set at 70 - 80 watts and an
      argon flow of 0.8 liters/minute. RESULTS: Complete and satisfactory trimming of
      the stents was possible, without complications (mean follow-up 15.8 months), in
      all patients except one, a patient with a covered biliary Wallstent. In 13
      patients with biliary or Enteral Wallstents the trimming procedure was
      preventive. In eight patients with ulceration and/or hemorrhage (duodenal or
      rectal), healing was achieved after stent trimming and epinephrine (adrenaline)
      injection followed by electrocoagulation. Stent trimming restored patency of the
      duodenal lumen in six patients and of the esophageal lumen in two patients, and
      was done to allow insertion of a biliary stent in one patient whose duodenal
      stent was covering the papilla. In one patient with rectal tenesmus, stent
      shortening resulted in complete resolution of symptoms. CONCLUSIONS: Endsocopic
      plasma argon trimming of metallic stents is an efficient procedure which allows
      easy, reproducible and well-tolerated correction of complications that arise due
      to these prostheses.

PMID- 15844022
TI  - Endoscopic biliary drainage by nasobiliary drain or by stent placement in
      patients with acute cholangitis.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic biliary drainage is an established mode of
      treatment for acute cholangitis. We compared the safety and efficacy of
      nasobiliary drain (NBD) placement and stent placement for biliary drainage in
      patients with acute cholangitis. PATIENTS AND METHODS: We recruited a total of
      150 patients with severe cholangitis who required endoscopic biliary drainage.
      Patients were randomized to have either a 7-Fr NBD or a 7-Fr straight flap stent
      placed during endoscopy. Outcome measures included complications related to
      endoscopic retrograde cholangiopancreatography (ERCP) and the clinical outcome.
      RESULTS: Of the 150 patients, 75 were randomized to the NBD group and 75 to the
      stent group. The most common causes of biliary obstruction were common bile duct
      stones (n = 102) and biliopancreatic malignancies (n = 37). The site of the
      biliary obstruction was predominantly found to be the lower part of common bile
      duct in both the NBD group (n = 58) and the stent group (n = 59). Indications for
      biliary drainage were: a fever of > 100.4 degrees F (n = 140), hypotension (n =
      23), peritonism (n = 40), impaired consciousness (n = 29), and failure to improve
      with conservative management (n = 45). Biliary drainage was achieved in 147
      patients. Abdominal pain, fever, jaundice, hypotension, peritonism and altered
      sensorium improved after a median period of 2 days in both groups. Leukocyte
      counts became normal after a median time of 7 days in the NBD group and 6 days in
      the stent group. There were no ERCP-related complications. There were no
      instances of displacement or kinking of an NBD, occlusion of an NBD or stent, or
      of stent migration. Four patients died (two in the NBD group and two in the stent
      group) as a result of uncontrolled cholangitis after 1, 2, 4, and 6 days of
      biliary drainage. The success rates of biliary drainage in cholangitis were not
      affected by the type of endoprosthesis used (72/74 for NBD patients vs. 71/73 for
      stent patients), the etiology of the biliary obstruction (110/112 for benign
      obstruction vs. 33/35 for malignant obstruction), or the site of the biliary
      obstruction (28/30 for upper common bile duct obstruction vs. 115/117 for
      obstruction at the lower end of common bile duct). CONCLUSIONS: Biliary drainage
      by nasobiliary drain and drainage by stent are equally safe and effective
      treatments for patients with severe cholangitis.

PMID- 15844023
TI  - Follow-up after endoscopic snare resection of duodenal adenomas.
AB  - BACKGROUND AND STUDY AIMS: Premalignant duodenal polyps are considered to be
      rare. Recurrence after local excision is reported to be frequent, so many authors
      propose radical surgical treatment of these tumors. The aim of this study was to
      determine the long-term outcome after endoscopic resection of duodenal adenomas.
      PATIENTS AND METHODS: Between January 1990 and April 2003 we retrospectively
      evaluated a group of patients who presented with nonampullary duodenal villous
      tumors but who did not have a polyposis syndrome. RESULTS: Duodenal polyps were
      diagnosed in 21 patients during routine endoscopy during the study period. Of
      these, 18 patients (6 men, 12 women; median age 67, range 50 - 81), with a total
      of 20 duodenal adenomas, were enrolled into the study. The median size +/- SD of
      the tumors was 27.5 +/- 12 mm (range 8 - 50 mm). Of these 20 tumors, 18 adenomas
      were tubulovillous, one was tubulous and one was villous. Nineteen polyps were
      treated by snare excision and one adenoma was treated with argon plasma
      coagulation alone. Argon plasma coagulation was applied to polyps in six patients
      after snare excision during this initial treatment phase. The success rate for
      endoscopic adenoma removal after a 3-month interval was 55 %. After a median
      follow-up period of 71 months (range 22 - 151 months), 12 patients remained in
      remission. Local recurrences of the lesion occurred in five patients (25 %) and
      these were re-treated. None of the patients developed carcinoma during the follow
      up period. CONCLUSIONS: Endoscopic snare excision of duodenal adenomas is an
      effective mode of treatment but an endoscopic surveillance program is mandatory
      in order to detect and treat recurrence.

PMID- 15844024
TI  - Endoscopic management and follow up of Dieulafoy lesion in the upper
      gastrointestinal tract.
AB  - BACKGROUND AND STUDY AIMS: Dieulafoy's lesion is an important cause of upper
      gastrointestinal bleeding, and the safety and efficacy of endoscopic treatment
      have been widely accepted. The aim of this study was to evaluate the
      effectiveness of endoscopic management, including hemoclipping and injection
      methods, for bleeding Dieulafoy lesions in the upper gastrointestinal tract.
      PATIENTS AND METHODS: Between 1995 and 2003, 61 patients with bleeding Dieulafoy
      lesions underwent endoscopic treatment. The available hemostatic methods were
      hemoclipping, hypertonic saline-epinephrine injection, and pure ethanol
      injection. Clinical data, endoscopic features, and treatment outcome were
      analyzed retrospectively. RESULTS: Comorbid conditions were present in 39
      patients (64 %). Active bleeding was noted in 20 patients (33 %). Hemoclipping
      was a selected treatment in 48 patients (79 %). Initial hemostasis was achieved
      in 61 patients (100 %). One patient had rebleeding 6 days after the initial
      procedure but was successfully treated endoscopically. The 30-day mortality was 0
      %. During follow-up, for a mean of 47 months, 15 patients (25 %) died of causes
      unrelated to the Dieulafoy lesion. Two patients had recurrent bleeding due to non
      Dieulafoy gastric ulcer, and responded to endoscopic therapy. We encountered no
      patients who required surgery. CONCLUSIONS: Dieulafoy lesion can be successfully
      managed by endoscopic treatment. The long-term outcome is acceptable.

PMID- 15844025
TI  - Colonic changes in patients with cirrhosis and in patients with extrahepatic
      portal vein obstruction.
AB  - BACKGROUND AND STUDY AIMS: Figures for the prevalence of anorectal varices and
      portal hypertensive colopathy have varied considerably in the available studies
      of patients with cirrhosis, and few studies have observed these changes in
      patients with extrahepatic portal vein obstruction (EHPVO). Our aim was to
      investigate the colonic changes, if any, in patients with EHPVO and to compare
      them with those seen in patients with cirrhosis of the liver. PATIENTS AND
      METHODS: A total of 50 patients with cirrhosis and 35 patients with EHPVO, all of
      whom had a history of at least one episode of bleeding from esophageal varices,
      underwent both upper gastrointestinal endoscopy and colonoscopy. RESULTS:
      Anorectal varices were seen more commonly in patients with EHPVO than in patients
      with cirrhosis (63 % vs. 38 %, P < 0.03). Of the patients with anorectal varices,
      large anorectal varices were also more common in patients with EHPVO than in
      patients with cirrhosis (73 % vs. 32 %, P < 0.01). Colopathy was noted in 40 % of
      patients with EHPVO and in 62 % of patients with cirrhosis (P < 0.05). Of the
      patients with EHPVO, colopathy was noted in 27 % of patients who also had
      anorectal varices and in 61.5 % of patients without anorectal varices (P < 0.05).
      Similarly, patients with both cirrhosis and anorectal varices were found to have
      a lower prevalence of colopathy than cirrhotic patients without anorectal varices
      (42 % vs. 74 %, P < 0.03). CONCLUSIONS: Anorectal varices are more common in
      patients with EHPVO, while portal hypertensive colopathy is more common in
      patients with cirrhosis. Large anorectal varices are also more common in patients
      with EHPVO than in patients with cirrhosis and there is an inverse relationship
      between anorectal varices and colopathy in both cirrhotic patients and patients
      with EHPVO.

PMID- 15844026
TI  - Prospective comparison of cardiopulmonary events during minilaparoscopy and
      colonoscopy under conscious sedation.
AB  - BACKGROUND AND STUDY AIMS: Cardiorespiratory parameters were examined throughout
      diagnostic minilaparoscopy procedures. The same parameters were analyzed during
      colonoscopy, and the data were compared. PATIENTS AND METHODS: Sixty-five
      consecutive unselected patients undergoing minilaparoscopy (group 1: ASA I, n =
      34; group 2: ASA II/III, n = 31) and 61 consecutive unselected patients
      undergoing colonoscopy (group 3: ASA I, n = 31; group 4: ASA II/III, n = 30) were
      included. Oxygen saturation (Sao (2)), heart rate (HR) and mean arterial pressure
      (RRm) were measured continuously, and 12-lead electrocardiography (ECG)
      recordings were made at specific times during each procedure. RESULTS: Minor
      differences were observed, particularly after premedication, probably due to
      different dosage regimens and timing in the two examination techniques. After
      premedication, testing for differences from baseline values showed a minor
      decrease in Sao (2) and RRm in the minilaparoscopy groups in comparison with the
      colonoscopy groups (median Sao (2), group 1: 99.9 % +/- 0 vs. group 3 : 100 % -1,
      P = 0.0078; median RRm, group 1: 99.5 - 4 mm Hg vs. group 3 : 96 -16 mm Hg, P =
      0.046, and median RRm, group 2 : 110 + 1 mm Hg vs. group 4 : 101 -13.5 mm Hg, P =
      0.0007). HR increased in minilaparoscopy in comparison with colonoscopy (median
      HR: group 2 : 77 + 4 beats/min vs. group 4 : 75.5 +/- 0 beats/min; P = 0.01).
      Comparison of defined relevant pathological changes in Sao (2), RRm, HR, and ECG
      showed no significant differences. DISCUSSION: These data indicate that
      diagnostic minilaparoscopy under conscious sedation is only associated with
      limited risk in patients with compensated cardiopulmonary diseases. This is
      probably due to the low insufflation pressure used.

PMID- 15844027
TI  - Ileocolonic lymphomas: a series of 16 cases.
AB  - BACKGROUND: Colonoscopic and clinical differences between primary ileocolonic
      mucosa-associated lymphoid tissue (MALT) lymphoma and mantle cell lymphoma (MCL)
      have not been defined. METHODS: We reviewed colonoscopic and clinical features in
      eight patients with primary MALT lymphoma and eight patients with MCL in the
      terminal ileum and/or colorectum. All cases were examined for CD5 and/or cyclin
      D1 expression. RESULTS: Endoscopic features of MALT lymphoma were characterized
      as protrusions that were covered with normal-appearing mucosa with or without
      ulceration. The gross appearances of MALT lymphomas were categorized as solitary
      (4 patients), multiple (3 patients), and multiple lymphomatous polyposis (MLP) (1
      patient). The gross features of MCL at endoscopy were categorized as multiple
      protrusions (2 patients), and MLP (6 patients). The clinical stages of patients
      with MCL were more advanced than in patients with MALT lymphoma. CONCLUSIONS:
      Solitary or multiple protrusions at an early clinical stage is the most common
      presentation pattern of patients with MALT lymphoma, but an MLP appearance at an
      early stage is also possible. On the other hand, MLP appearance with an advanced
      clinical stage is the main presentation pattern in patients with MCL, although
      multiple protrusions with an early clinical stage is also possible. Histological
      and immunohistochemical investigation including that of cyclin D1 and CD5
      expression is essential to make the final diagnosis.

PMID- 15844028
TI  - Endoscopic treatment of gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease is a common chronic disorder which has a severe
      effect on the patient's quality of life. In view of the high cost of medical
      therapy and the limitations of surgery, a variety of endoscopic techniques have
      been developed for the treatment of this condition, and these have shown
      apparently encouraging results, at least in the short term. However, promising
      results have been obtained in only around two-thirds of patients over a short
      term follow-up period of about 6 months. Moreover, several inconsistencies have
      emerged between the efficacy of this form of treatment in improving symptoms and
      quality of life and a lack of improvement of objective parameters, such as lower
      esophageal sphincter pressure and esophageal acid exposure. The authors strongly
      endorse the need for comprehensive evaluation of clinical evidence on this topic.
      After an extensive evaluation of existing literature, we suggest that controlled
      studies are urgently needed in order to clarify the potential of endoscopic
      therapy, either in terms of cost-effectiveness or in comparison with standard
      therapy. Meanwhile, with regard to current practice, the use of endoscopic
      treatment should be limited to clinical trials, which should incorporate the
      provision of comprehensive and unbiased information to study patients.

PMID- 15844029
TI  - Techniques using the hemoglobin index of the gastric mucosa.

PMID- 15844030
TI  - Endoscopic ultrasound-guided bile duct access for rendezvous ERCP drainage in the
      setting of intradiverticular papilla.
AB  - Cannulation of an intradiverticular papilla during endoscopic retrograde
      cholangiopancreatography (ERCP) can be challenging. We present here a technique
      for endoscopic ultrasound-guided puncture of the common bile duct followed by
      rendezvous ERCP for biliary drainage through the native intradiverticular
      papilla.

PMID- 15844031
TI  - Phlegmonous gastritis after endoscopic mucosal resection.

PMID- 15844032
TI  - Three-point fixation of stomach to abdominal wall in the percutaneous endoscopic
      gastrostomy procedure.

PMID- 15844033
TI  - A new band deployment system: do we really need two threads?

PMID- 15844035
TI  - Traumatic incomplete rupture of the gastric wall: endoscopic treatment with clip
      application.

PMID- 15844034
TI  - Infected liver cyst after adrenaline injection for active duodenal ulcer.

PMID- 15844036
TI  - Choledochal cystadenoma.

PMID- 15844037
TI  - Endoscopic management of patients with familial adenomatous polyposis (FAP)
      following a colectomy.

PMID- 15844038
TI  - [Surgical approach to retinal vein occlusion].
AB  - Retinal vein occlusions are the second most common vision threatening retinal
      vascular disorders. Our therapeutic armamentarium for functional improvement was
      very limited in the past for all types of retinal vein occlusions (branch,
      central and hemi-central retinal vein occlusion). Also pathomechanism and risk
      factors are not completely understood yet. Argon-laser-photocoagulation can
      prevent the development and treat neovascularizations successfully, but is unable
      to improve visual function in most cases. Thrombolytic therapy applied
      systemically is limited due to serious side effects but may be helpful when
      injected intraocularly. Isovolemic hemodilution may be efficacious in central
      retinal vein occlusion (CRVO). The creation of a laser-induced chorioretinal
      venous anastomosis showed serious complications. Since 1999 numerous reports on
      successful surgical techniques were published. It could be shown that the
      dissection of the adventitial sheath with separation of the artery from the vein
      at the arteriovenous crossing where branch retinal vein occlusion occurs can re
      establish the retinal blood flow with reduction of macular edema. But it is still
      unclear which step of the surgery (vitrectomy, ILM-peeling, sheathotomy) is
      causative for the results. A new surgical approach in CRVO is the radial optic
      neurotomy (RON). This technique was primarily performed under the hypothesis of
      decompression of the central vein by cutting the scleral ring. Meanwhile there is
      some evidence that the formation of chorioretinal shunts may be the decisive
      factor in cases of successfully performed RON. Due to inconsistent and rare data
      this surgical procedure needs further evaluation. Another surgical option is the
      cannulation of the occluded vein. This technique seems to be feasible but the
      clinical results still have to be proved. Despite several uncertainties and open
      questions, surgical techniques are likely to overcome the desolate therapeutic
      situation for retinal vein occlusion of the past.

PMID- 15844039
TI  - [Substances for staining biological tissues: use of dyes in ophthalmology].
AB  - The azo dye trypan blue and the cyanine dye indocyanine green have been used in
      ophthalmology since the 1980 s to dye the anterior capsule in cataract operations
      and to stain epiretinal membranes in order to remove the membrana limitans
      interna (ILM). By means of a standardized in vitro test in accordance with DIN EN
      ISO 10993, it has now been shown that both dyes and the theoretically possible
      alternatives - the anthrachinone alizarincyanine green and the trityl dyes fast
      green and lissamine green - are cytotoxic in the normal concentrations of maximum
      1.5 g/l. On the other hand, the new product Blueron(R) with the trityl dye patent
      blue, which has been developed to dye the anterior capsule, is completely
      biocompatible, even at a high dosage of up to 2.8 g/l.

PMID- 15844040
TI  - [NF2: ocular, neural and genetic manifestations].
AB  - Neurofibromatosis 2 is an autosomal-dominant disease, which is characterized by
      vestibular schwannomas, cataract, retinal hamartomas as well as tumors of the
      peripheral and central nerve system, demonstrating a variety of expression. The
      ophthalmologist plays an important role in making the diagnosis, as several
      ocular manifestations may be shown during childhood, before tumors of the central
      nerve system become symptomatic. An early diagnosis of NF 2 may prevent deafness
      by early surgical intervention. Due to primary and secondary reasons such as age
      related processes, different sensations like hearing or vision may be
      compromised. Neuropathy may lead to vestibular disturbances and loss of muscle
      control. Therapeutic options include cataract surgery, implantation of cochlear
      or brainstem implants as well as conservative therapy of the ocular surface in
      paresis of the VIIth cranial nerve or learning to read from the lips. The human
      NF2 gene was cloned from chromosome 22 in 1993. The major part of the genetic
      alterations described so far are point mutations as well as deletions or
      insertions in or around the exons. Geno-phenotype correlations allow some
      predictions of the course of the disease to be made.

PMID- 15844041
TI  - ["Talking Eyes" versus "Silent Ophthalmoscopy"?].

PMID- 15844042
TI  - [Telemedical-supported screening of retinal vessels ("talking eyes")].
AB  - BACKGROUND: Cerebral and retinal vessels behave similarly under the influence of
      vascular risk factors. Several groups have shown that retinal microvascular
      abnormalities represent an independent risk factor with regard to strokes and
      heart attacks. AIM OF THE STUDY: The aim of this study was to perform a
      prospective screening examination with regard to retinal microvascular
      abnormalities as well as an extended vessel diagnosis in a subgroup of patients
      with lower arteriovenous risk values. METHODS: In the course of a prospective
      cross-sectional study ("Talking Eyes") between 1.9.2001 and 1.8.2002 a
      telemedical-supported screening of the retina (study I) was carried out in 7,163
      subjects. The patients were selected without any inclusion or exclusion criteria.
      The mean age was 48.2 +/- 8 years (18 - 83 years) with a sex distribution of 39.2
      % females to 60.8 % males. Digital fundus photos of the right and left eyes were
      taken for all patients. The pictures were taken without pupil dilation using a
      CANON-NM camera. The pictures and case histories were stored in a central server
      using web-based software (MedStage, Siemens). In a central reading centre, the
      arteriovenous ratio of both eyes was determined telemedically using the Parr
      Hubbard formula and the retinas subjected to a standardised examination by an
      ophthalmologist. The retinal risk factor was calculated on the basis of the
      arteriovenous ration, the presence of microvascular abnormalities and the case
      history. The reproducibility of measurement of the arteriovenous ratio (Kronbach
      alpha coefficient) was evaluated by double measurements on 1,332 images. In a
      subgroup of study I with arteriovenous ratio values < 0.76 (N = 107), an extended
      vessel diagnosis with measurement of 24-h blood pressure and vessel-relevant
      blood values (homocysteine, cholesterol, LDL, HDL, CRP, TG, HbA1c) was carried
      out (study II). RESULTS: Study I: The Kronbach alpha coefficient as a measure of
      reproducibility amounted to 0.77. The mean arteriovenous ratio of the retinal
      vessels was 0.83 +/- 0.09 and showed a pronounced age dependence (R = 0.9, p <
      0.0001). On multivariate testing the arteriovenous ratio correlated significantly
      (R = 0.33, p < 0.001) with the factors age, systolic blood pressure, diastolic
      blood pressure and body mass index. Diastolic blood pressure followed by age had
      the largest influence. The prevalence of microvascular abnormalities in the right
      (RE) and left (LE) eyes, respectively were: cotton wool foci RE 0.0015 %, LE
      0.003 %, retinal haemorrhage RE 0.1 %, LE 0.1 %, focal stenoses RE 3.4 %, LE 3.4
      %, tortuositas vasorum RE 4.1 %, LE 4.0 %, arteriovenous crossing signs RE 11.2
      %, LE 11.2 %. On multivariate testing the occurrence of microvascular
      abnormalities correlated significantly (R = 0.38, p < 0.001) with the factors
      high blood pressure known from case history, body mass index, and gender.
      Arterial hypertension had the strongest influence followed by diastolic blood
      pressure. The calculated retinal risk factor correlated with the prevalence of
      angina pectoris. Study II: 2/3 of the subjects with arteriovenous risk factor
      values < 0.76 exhibited pathologically high 24-h blood pressure values. For these
      patients there were significant correlations between the arteriovenous ratio and
      the low-density lipoprotein concentration as well as the Framingham risk score.
      CONCLUSION: In the course of a prospective, telemedical-supported screening
      examination of the retinal vessels of more than 7,000 subjects the arteriovenous
      ratio exhibited a strong dependence on age and blood pressure. Among the subjects
      with lowered arteriovenous ratio values, 2/3 exhibited arterial hypertension in
      the 24-h blood pressure determination.

PMID- 15844043
TI  - [Long-term results after selective laser trabeculoplasty -- a clinical study on
      269 eyes].
AB  - BACKGROUND: Selective laser trabeculoplasty SLT is a new method to reduce
      intraocular pressure in eyes with primary open angle glaucoma. With a Q-switched,
      frequency-doubled Nd:YAG laser it targets the pigmented trabecular meshwork cells
      without visible damage to the adjacent non-pigmented tissue. SLT acts non
      thermally, the intracellular microdisruptions triggered by the laser are confined
      to the targeted cells, the laser pulses are so short that heat created within the
      targeted cells does not have time to spread to the surrounding tissue. A clinical
      prospective study was conducted to evaluate the long-term results, safety and
      efficacy of SLT in the treatment of open angle glaucoma. PATIENTS AND METHODS:
      Since 2002, we have performed a selective laser trabeculoplasty in 269 eyes: in
      17 eyes with ocular hypertension, in 239 eyes with primary open angle glaucoma,
      in 11 eyes with low tension glaucoma, while 2 eyes had a secondary glaucoma due
      to uveitis. In 22 eyes the primary initial treatment was SLT. RESULTS: Three
      months after treatment, the mean IOP reduction from baseline was 3.4 mm Hg,
      respectively 15 %, after 12 months the mean IOP reduction was 3.0 mm Hg (12.9 %),
      and after 24 months 2.7 mm Hg or 12.1 %. The response curve of the eyes with
      ocular hypertension greatly resembled the eyes with primary open angle glaucoma
      and with low tension glaucoma. CONCLUSIONS: SLT has shown reasonable efficacy in
      lowering IOP in eyes with primary open angle glaucoma and ocular hypertension,
      both as a first-line treatment and as a treatment in medication-refractory eyes.
      SLT is effective for patients who have had prior treatment with ALT. Long-term
      follow-up studies are needed to determine whether the IOP lowering effect is
      sustained over time, and to assess the efficacy of repeated SLT. The exact
      biological effect induced with the SLT is still not understood.

PMID- 15844044
TI  - [The outcome of phacoemulsification in eyes after filtering glaucoma surgery].
AB  - BACKGROUND: Our aim was to evaluate the outcome of phacoemulsification in eyes
      after filtering glaucoma surgery. PATIENTS AND METHODS: Thirty eyes of 30
      patients with different forms of glaucoma in which phacoemulsification after
      filtering glaucoma surgery was done were included in this retrospective study.
      Intraocular pressure (IOP) was measured before and one week, 1, 3, 6, 12, 18, 24,
      30, 36 and 42 months after phacoemulsification. The best corrected visual acuity
      (BCVA) and the number of antiglaucoma medications before phacoemulsification and
      at the end of follow-up were evaluated. Partial failure of IOP control was
      defined as the need for an increased number of antiglaucoma medications to
      maintain IOP < 21 mmHg or prevent a progression of visual field or optic disc
      damage. Complete failure of IOP control was defined as an IOP > 21 mmHg with an
      additional number of antiglaucoma medications or a progression of visual field or
      optic disc damage requiring filtering surgery. RESULTS: The mean interval between
      filtration surgery and phacoemulsification was 5.8 years (SD 3.8) and the mean
      follow-up after phacoemulsification was 23.4 months (SD 11.4). There were no
      differences between the mean IOP before and after phacoemulsification during the
      entire follow-up period (p > 0.05). The mean preoperative BCVA was 0.30 (SD 0.2),
      improving to a mean of 0.72 (SD 0.3) postoperatively at the end of follow-up (p <
      0.0001). The mean number of antiglaucoma medications before phacoemulsification
      was 1.2 (SD 1.2), increasing after phacoemulsification to 1.5 (SD 1.2) at the end
      of follow-up (p > 0.05). In 9 eyes a partial failure of IOP control was assessed,
      so according to the Kaplan-Meier survival analysis the success rate after 12
      months was 72 % and after 42 months 67 %. In 3 eyes a complete failure of IOP
      control was assessed, thus according to the Kaplan-Meier survival analysis the
      success rate after 22 months was 93 % and after 42 months 77 %. CONCLUSION:
      Phacoemulsification in eyes after filtering glaucoma surgery resulted in a stable
      IOP, a non-significant increase in the number of antiglaucoma medications and a
      significantly improved BCVA.

PMID- 15844045
TI  - [Age-related macula degeneration and diabetic retinopathy -- differences in optic
      rehabilitation].
AB  - BACKGROUND: Age-related macular degeneration (AMD) and diabetes mellitus are the
      major contributing causes of visual impairment in the industrial nations. This
      study shows how far visual acuity (VA) and magnification demand (MD) influence
      the selection of suitable low vision aids. Based on this information, differences
      regarding the spectrum of prescribed magnifying devices between both patient
      groups will be presented. MATERIALS AND METHODS: Between January 2003 and October
      2004, a total of 2500 patients was seen in our Low Vision Department. Among them
      were 1198 patients with AMD (48 %) and 296 visually impaired patients because of
      diabetic ocular involvement (12 %). In every patient, best corrected distance and
      near VA as well as the required MD were measured. Finally, matching of magnifying
      aids and discussing aspects of professional and social rehabilitation were the
      main parts of our interdisciplinary Low Vision Service. RESULTS: In AMD patients,
      the average of best corrected distance VA at the better eye was 0.24, the best
      corrected near VA was 0.19. In diabetes patients, the average of best corrected
      distance VA at the better eye was 0.28, the best corrected near VA was 0.22. The
      required mean MD was 4.0 x (related to the reading of newspaper text) compared to
      7.6 x in patients with AMD. In 94 % of the visually impaired diabetes patients,
      optical magnifiers could be prescribed (e. g. magnifying eyeglasses, telescopes,
      monoculars, Galelean and Keplerian systems), whereas electronic devices were
      necessary in only 6 %. In comparison, 14.8 % of the patients with AMD had to be
      provided with electronic systems. CONCLUSIONS: In 94 % of the visually impaired
      patients caused by diabetes, reading ability could be restored using optical low
      vision aids. In AMD patients, this could be achieved in only 85.2 %. This fact
      can mainly be explained with the negative effect of absolute central scotomas on
      reading speed in AMD patients which leads, compared to diabetes patients, to
      elevated magnification factors. Therefore, the choice of certain magnifying
      devices depends not only on VA, but has mainly to be evaluated based on the
      individual MD.

PMID- 15844046
TI  - [Rubeosis iridis (neovascularisation on the iris)].

PMID- 15844047
TI  - [Iris neovascularization as a complication of central artery occlusion].
AB  - BACKGROUND: Iris neovascularization (IN) with a secondary angle closure glaucoma
      is a complication of central retinal artery occlusion (CRAO). Its incidence is
      greatly underestimated. MATERIALS AND METHODS: In a retrospective study we
      analyzed all patients with CRAO seen within 2 years who were treated in our
      department. We looked especially for the frequency of the occurrence of IN.
      RESULTS: In 27 patients with CRAO, 5 developed an IN with a secondary neovascular
      glaucoma with high intraocular pressure. Thus, the frequency of IN was 18 % in
      our patients. The IN occurred 2 months to 2 years after the occlusion. Visual
      acuity in three eyes was between 1/20 and light perception and two eyes had no
      light perception. In all cases a panretinal laser treatment was performed. Three
      eyes were additionally treated with a peripheral retinal cryocoagulation and
      cyclophotocoagulation. In the histories of these patients, diabetes mellitus and
      arterial hypertension were found. CONCLUSIONS: In previous studies it has been
      shown, that ischemia/reperfusion injuries of the retina after CRAO predispose to
      IN (incidence 3 - 18 %). Although it has been shown that the majority of IN
      occurs within three months, our data show that IN may occur as a severe
      complication of CRAO even later. Patients should be followed-up closely
      (including gonioscopy), to diagnose the occurrence of IN early. Recommended
      treatment is panretinal laser coagulation or -- in the case of a secondary angle
      closure glaucoma -- cyclophotocoagulation, respectively.

PMID- 15844048
TI  - [Uveitis in childhood sarcoidosis].

PMID- 15844049
TI  - [Uveitis in childhood sarcoidosis].
AB  - BACKGROUND: Sarcoidosis is a rare cause of uveitis in childhood. Differentiation
      from other rheumatic diseases may be difficult. We report on five children with
      uveitis in childhood sarcoidosis and review the previous literature. RESULTS:
      Children were aged between seven month and 13 years at the time of diagnosis of
      uveitis. Four of the five patients had panuveitis, the fifth one had intermediate
      uveitis. In addition, three children had systemic disease with skin, joint and
      central nervous system involvement. The two children younger than 5 years showed
      the clinical triad of eye, joint and skin disease. Uveitic complications included
      corneal band keratopathy, cataract, posterior synechiae, macular scars and
      choroidal neovascularisation. Vision-limiting complications were found in six of
      nine eyes at the first visit. CONCLUSION: In childhood sarcoidosis two clinical
      courses can be differentiated. Younger children aged up to five years express a
      clinical triad of arthritis, skin lesions and uveitis. In the older group of
      patients, the clinical course is more similar to that of adults. Rapid diagnosis
      and quiescence of disease are of particular importance to improve the long-term
      visual prognosis.

PMID- 15844050
TI  - [Does insulin glargin (lantus) lead to a progression in diabetic retinopathy?].

PMID- 15844051
TI  - [In memorium: prof. Theo N. Waubke, MD].

PMID- 15844052
TI  - [Evidence based observations on accommodative artificial lenses].

PMID- 15844053
TI  - [Comment on the publication by C. Jandeck, U. Kellner, M. H. Foerster:
      "Retinopathy of prematurity"].

PMID- 15844055
TI  - Fatal necrotizing colitis following a foodborne outbreak of enterotoxigenic
      Clostridium perfringens type A infection.
AB  - BACKGROUND: Enterotoxigenic Clostridium perfringens type A is the third leading
      cause of foodborne disease in the United States, resulting annually in an
      estimated 250,000 cases of a typically mild, self-limiting gastrointestinal
      illness. METHODS: A retrospective cohort study was conducted to determine the
      cause of a small cluster of cases of gastrointestinal illness, which included
      cases of severe necrotizing colitis. Participants in the study consisted of
      residents and staff of a residential care facility for the mentally ill in
      Oklahoma (n = 20). An inspection of food preparation and food storage areas of
      the residential care facility was conducted as part of an environmental
      investigation. The investigation included extensive microbiological and molecular
      testing of the C. perfringens isolates and tissue specimens collected at autopsy.
      RESULTS: A total of 7 (3 confirmed and 4 probable) cases of foodborne
      enterotoxigenic C. perfringens type A were identified (attack rate, 35%) after
      the consumption of high-risk foods. Three residents developed acute necrotizing
      colitis; 2 of them died. Each patient with confirmed infection presented with
      evidence of constipation or fecal impaction. C. perfringens enterotoxin (CPE)
      positive C. perfringens type A was cultured on samples from each patient with
      necrotizing colitis. Although statistical analyses failed to implicate a food
      source, the isolates carried a chromosomal cpe gene, which supports a foodborne
      origin. CONCLUSIONS: This study confirms that foodborne CPE-positive C.
      perfringens type A can affect the colon, resulting in potentially fatal
      necrotizing colitis. Drug-induced constipation and fecal impaction, resulting in
      prolonged exposure of the colonic mucosal tissue to C. perfringens type A toxins,
      contributed to the development of necrotizing colitis.

PMID- 15844056
TI  - Escherichia coli: development of carbapenem resistance during therapy.
AB  - A 76-year-old woman had recurrent urosepsis due to extended-spectrum beta 
      lactamase-positive Escherichia coli. Imipenem resistance was detected after long
      term imipenem-meropenem therapy. The carbapenem-hydrolyzing enzyme gene was
      identified as blaKPC-3. To our knowledge, this is the first documented case in
      which carbapenem-resistant E. coli emerged during therapy with imipenem and
      meropenem, and the first identification of the carbapenem-hydrolyzing enzyme in
      E. coli isolates.

PMID- 15844057
TI  - Persistent culture-positive Legionella infection in an immunocompromised host.
AB  - Legionella pneumophila is an important cause of community-acquired and nosocomial
      pneumonia. We describe an immunocompromised patient with severe pneumonia from
      whom Legionella species were isolated from sputum samples by culture for 30 days,
      despite administration of treatment with appropriate antimicrobial agents.
      However, clear improvement in the patient's respiratory condition was evident,
      and he subsequently recovered completely.

PMID- 15844059
TI  - Guidelines for infectious diseases specialists serving as expert witnesses.

PMID- 15844058
TI  - Expert Witness Guidelines: it's our turn.

PMID- 15844061
TI  - Diagnostic accuracy of routine postoperative body temperature measurements.
AB  - BACKGROUND: On surgical wards, body temperature is routinely measured, but there
      is no proof that this is useful for detecting postoperative infection. The aim of
      this study was to compare temperature measurements (the test) with the confirmed
      absence or presence of a postoperative infection (the reference standard).
      METHODS: A prospective triple-blinded diagnostic study involving 308 consecutive
      patients was performed. A positive test result was defined as a postoperative
      temperature > or = 38.0 degrees C. The reference standard was considered to
      indicate a postoperative infection if results of a bacterial culture were
      positive or if an infection was suspected on clinical grounds. RESULTS: Data for
      284 of 308 patients were analyzed (2282 temperature measurements). The prevalence
      of infection was 7% (19 of 284 patients). The temperature curves of patients were
      used as units of analysis and revealed that a temperature > or = 38.0 degrees C
      had a sensitivity of 37% (95% confidence interval [CI], 0.16%-0.62%) and a
      specificity of 80% (95% CI, 0.75%-0.85%). The likelihood ratio for a positive
      test result was 1.8 (95% CI, 0.7-4.0) and for a negative test result was 0.8 (95%
      CI, 0.4-1.4). When all 2282 measurements were considered as independent test
      results, the positive predictive value was only 8% (95% CI, 5%-13%). Six of 8
      patients with a severe infection had temperatures < 38 degrees C. CONCLUSION:
      Routine measurement of body temperature is of limited value in the detection of
      infection after elective surgery for noninfectious conditions. Serious
      postoperative infections can even occur without an accompanying increase in
      temperature.

PMID- 15844060
TI  - Randomized, double-blind clinical trial of topical imiquimod 5% with parenteral
      meglumine antimoniate in the treatment of cutaneous leishmaniasis in Peru.
AB  - BACKGROUND: Current treatments for cutaneous leishmaniasis are limited by their
      toxicity, high cost, and discomfort and the emergence of drug resistance. New
      approaches, including combination therapies, are urgently needed. We performed a
      double-blind, randomized trial of therapy with parenteral antimony plus topical
      imiquimod, an innate immune-response modulator, versus therapy with antimony
      alone, in subjects with cutaneous leishmaniasis for whom an initial course of
      antimony therapy had failed. METHODS: Forty subjects with clinical resistance to
      antimony were recruited in Lima, Peru, between February 2001 and December 2002.
      All subjects received meglumine antimoniate (20 mg/kg/day im or iv) and were
      randomized to receive either topical imiquimod 5% cream (Aldara; 3M
      Pharmaceuticals) or vehicle control every other day for 20 days. Lesions and
      adverse events were evaluated during treatment and at 1, 2, 3, 6, and 12 months
      after the treatment period. RESULTS: The mean number of lesions was 1.2 per
      person; 71% of the lesions were facial and 76% were ulcerative. There were no
      major differences between the groups, and all but 2 subjects completed therapy.
      Mild adverse events were reported by 73% of the subjects, but only erythema
      occurred more commonly in the imiquimod group (P < or = .02). Lesions resolved
      more rapidly in the imiquimod group: 50% of the imiquimod group achieved cure at
      1 month after the treatment period versus 15% of the vehicle cream group (P < or
      = .02); 61% of the imiquimod group at 2 months versus 25% of the vehicle cream
      group (P < or = .03); and 72% of the imiquimod group at 3 months versus 35% of
      the vehicle cream group (P < or = .02). Residual scarring in the imiquimod group
      was less prominent than in the vehicle cream group. CONCLUSIONS: Combined
      antimony plus imiquimod treatment was well tolerated, accelerated healing of
      lesions, and improved scar quality. This therapy may have particular advantages
      for subjects with facial lesions.

PMID- 15844062
TI  - Should we measure body temperature for patients who have recently undergone
      surgery?

PMID- 15844063
TI  - Predictors and outcomes of candiduria in renal transplant recipients.
AB  - BACKGROUND: The epidemiology of candiduria in renal transplantation is unknown.
      METHODS: We performed a nested case-control study to evaluate the epidemiology of
      candiduria in renal transplant recipients at the University of Wisconsin
      (Madison) over an 8-year period. RESULTS: Renal transplantations were performed
      on 1738 patients during this period, 192 of whom had 276 episodes of candiduria.
      Candida glabrata, which was recovered from 98 (51%) of 192 case patients, was the
      most common pathogen identified. Most case patients were asymptomatic.
      Independent predictors of candiduria were female sex (odds ratio [OR], 12.5; 95%
      confidence interval [CI], 6.7-23.0), intensive care unit admission (OR, 8.8; 95%
      CI, 2.3-35.0), antibiotic use during the month before candiduria (OR, 3.8; 95%
      CI, 1.7-8.3), presence of an indwelling bladder catheter (OR, 4.4; 95% CI, 2.1
      9.4), diabetes (OR, 2.2; 95% CI, 1.3-3.9), neurogenic bladder (OR, 7.6; 95% CI,
      2.1-27), and malnutrition (OR, 2.4; 95% CI, 1.3-4.4). Log-rank testing of Kaplan
      Meier curves revealed that 60-day, 90-day, and cumulative survival rates were
      significantly different between case and control patients; there was no
      difference in the survival rate during the first 30 days after transplantation. A
      variety of regimens were used for treatment; 119 case patients (62%) underwent
      removal of the indwelling bladder catheter within 1 week after diagnosis of
      candiduria. Candiduria cleared in 148 case patients (77%). Treatment of
      candiduria was not associated with an improved survival rate. CONCLUSIONS:
      Candiduria occurs commonly in renal transplant recipients. Risk factors for
      candiduria in such persons are similar to those in hospitalized patients who have
      not received a transplant. Candiduria is associated with reduced survival rates
      among persons who have undergone renal transplantation; this is likely a marker
      for severity of illness. Treatment of asymptomatic candiduria in renal transplant
      recipients does not appear to result in improved outcome.

PMID- 15844064
TI  - Genital tract shedding of herpes simplex virus type 2 in women: effects of
      hormonal contraception, bacterial vaginosis, and vaginal group B Streptococcus
      colonization.
AB  - BACKGROUND: Genital infections due to herpes simplex virus type 2 (HSV-2) are
      characterized by frequent reactivation and shedding of the virus and by the
      attendant risk of transmission to sexual partners. We investigated the effects of
      vaginal coinfections and hormonal contraceptive use on genital tract shedding of
      HSV-2 in women. METHODS: A total of 330 HSV-2-seropositive women were followed
      every 4 months for a year. At each visit, one vaginal swab specimen was obtained
      for detection of HSV-2 by polymerase chain reaction, a second vaginal swab
      specimen was obtained for detection of group B Streptococcus (GBS) organisms and
      yeast by culture, and a vaginal smear was obtained for the diagnosis of bacterial
      vaginosis by Gram staining. RESULTS: HSV-2 DNA was detected in 88 (9%) of 956
      vaginal swab specimens. Independent predictors of genital tract shedding of HSV-2
      were HSV-2 seroconversion during the previous 4 months (adjusted odds ratio
      [aOR], 3.0; 95% confidence interval [CI], 1.3-6.8), bacterial vaginosis (aOR,
      2.3; 95% CI, 1.3-4.0), high-density vaginal GBS colonization (aOR, 2.2; 95% CI,
      1.3-3.8), and use of hormonal contraceptives (aOR, 1.8; 95% CI, 1.1-2.8).
      CONCLUSIONS: The present study identifies hormonal contraceptive use, bacterial
      vaginosis, and high-density vaginal GBS colonization as risk factors for genital
      tract shedding of HSV-2 in women. Because hormonal contraceptives are used by
      millions of women worldwide and because bacterial vaginosis and vaginal GBS
      colonization are common vaginal conditions, even modest associations with HSV-2
      shedding would result in substantial attributable risks for transmission of the
      virus.

PMID- 15844065
TI  - Use of long-acting tetracyclines for methicillin-resistant Staphylococcus aureus
      infections: case series and review of the literature.
AB  - BACKGROUND: Few data exist on the efficacy of the long-acting tetracyclines
      doxycycline and minocycline against methicillin-resistant Staphylococcus aureus
      (MRSA) infection. METHODS: The medical records of 24 patients with serious
      tetracycline-susceptible MRSA infections who were treated with doxycycline or
      minocycline were reviewed. A review of the literature on the use of these
      antibiotics for treatment of both methicillin-susceptible and methicillin
      resistant S. aureus infection was also performed. RESULTS: Complicated skin and
      skin-structure infections were most common (67%). Clinical cure was achieved in
      20 (83%) of 24 patients in our case series. Both drugs were well-tolerated. The
      review of the literature on a total of 85 patients with S. aureus infection
      revealed similar results. CONCLUSIONS: Long-acting tetracyclines may be a
      reasonable treatment alternative for patients with certain types of MRSA
      infection.

PMID- 15844066
TI  - Lymphangitis-associated rickettsiosis, a new rickettsiosis caused by Rickettsia
      sibirica mongolotimonae: seven new cases and review of the literature.
AB  - BACKGROUND: Rickettsia sibirica mongolotimonae has been found in Hyalomma ticks
      in Inner Mongolia (in China) and Niger and in humans in France and South Africa.
      To date, only 3 cases of human infection have been reported. METHODS: Patients
      received a diagnosis of R. sibirica mongolotimonae infection on the basis of
      culture and/or PCR results plus serological test results. RESULTS: From January
      2000 to June 2004, R. sibirica mongolotimonae infection was diagnosed in 7
      patients. In 3 patients, the bacterium was cultivated from the inoculation
      eschar. The other 4 patients had cases that were diagnosed with use of PCR of
      samples obtained from the eschar (2 patients) or blood (2 patients), plus
      specific Western blot before (2 patients) and after (2 patients) cross
      adsorption. The clinical presentation included fever (temperature, >38.5 degrees
      C), a maculopapular rash, and > or =1 inoculation eschar in 6 patients, enlarged
      regional lymph nodes in 4 patients, and lymphangitis in 3 patients. On the basis
      of the study of 9 cases, R. sibirica mongolotimonae infection differed from other
      tick-borne rickettsioses in the Mediterranean area in the following ways: it
      involved a specific incidence in the spring, the presence of 2 eschars in 2 (22%)
      of the patients, the presence of a draining lymph node in 5 (55%) of the
      patients, and lymphangitis expanding from the inoculation eschar to the draining
      node in 4 (44%) of the patients. The most recent patient in our series received a
      clinical diagnosis on the basis of such findings. All patients recovered without
      any sequelae. CONCLUSIONS: We propose that this new rickettsiosis be named
      "lymphangitis-associated rickettsiosis." Lymphangitis-associated rickettsiosis
      should be considered in the differential diagnosis of tick-borne rickettsioses in
      Europe, Africa, and Asia.

PMID- 15844067
TI  - Risk factors for Buruli ulcer disease (Mycobacterium ulcerans Infection): results
      from a case-control study in Ghana.
AB  - BACKGROUND: Morbidity due to Buruli ulcer disease (BUD), a cutaneous infection
      caused by Mycobacterium ulcerans, has been increasingly recognized in rural West
      Africa. The source and mode of transmission remain unknown. METHODS: To identify
      BUD risk factors, we conducted a case-control study in 3 BUD-endemic districts in
      Ghana. We enrolled case patients with clinically diagnosed BUD and obtained skin
      biopsy specimens. M. ulcerans infection was confirmed by at least 1 of the
      following diagnostic methods: histopathologic analysis, culture, polymerase chain
      reaction, and Ziehl-Neelsen staining of a lesion smear. We compared
      characteristics of case patients with confirmed BUD with those of age- and
      community-matched control subjects using conditional logistic regression
      analysis. RESULTS: Among 121 case patients with confirmed BUD, leg lesions (49%)
      or arm lesions (36%) were common. Male case patients were significantly more
      likely than female case patients to have lesions on the trunk (25% vs. 6%; P =
      .009). Multivariable modeling among 116 matched case-control pairs identified
      wading in a river as a risk factor for BUD (odds ratio [OR], 2.69; 95% confidence
      interval [CI], 1.27-5.68; P = .0096). Wearing a shirt while farming (OR, 0.27;
      95% CI, 0.11-0.70; P = .0071), sharing indoor living space with livestock (OR,
      0.36; 95% CI, 0.15-0.86; P = .022), and bathing with toilet soap (OR, 0.41; 95%
      CI, 0.19-0.90; P = .026) appeared to be protective. BUD was not significantly
      associated with penetrating injuries (P = .14), insect bites near water bodies (P
      = .84), bacille Calmette-Guerin vaccination (P = .33), or human immunodeficiency
      virus infection (P = .99). CONCLUSIONS: BUD is an environmentally acquired
      infection strongly associated with exposure to river areas. Exposed skin may
      facilitate transmission. Until transmission is better defined, control strategies
      in BUD-endemic areas could include covering exposed skin.

PMID- 15844068
TI  - History of syphilis.
AB  - Evidence-based research now allows clear separation of syphilis from other
      diseases in its class of treponematoses. Examination of skeletons from
      populations with clinically diagnosed bejel and yaws revealed bone alterations
      distinctive to those diseases, clearly separating them from alterations due to
      syphilis, transcending the limitations of current DNA and immunologic
      technologies. These insights allowed confident identification of the New World
      origin of syphilis. Absence of skeletal evidence of any treponemal disease in
      continental Europe before the time of Columbus excludes it as site of origin of
      syphilis. Treponemal disease appears to have originated in East Africa with late
      transmission to England, perhaps as a complication of the slave trade. The
      original treponemal disease apparently spread from Africa through Asia, entering
      North America. Approximately 8 millennia later, it mutated to syphilis. Presence
      of skeletal evidence of syphilis at the site in the Dominican Republic where
      Columbus landed suggests the route by which it was transmitted to the Old World.

PMID- 15844069
TI  - Is it time to abandon the use of amphotericin B bladder irrigation?
AB  - In this article, we review the issues surrounding funguria and its management.
      With this background, the value of bladder irrigation with amphotericin B for the
      management of funguria is directly examined. Amphotericin B bladder irrigation is
      used frequently in clinical practice. Although its use is not standardized, there
      are multiple studies that attempt to show the impact on funguria management.
      These bladder irrigations have been used either for treatment of funguria or
      (less commonly) as a diagnostic test in attempts to identify upper urinary tract
      disease. Despite their widespread therapeutic use and relative safety, it is not
      clear from our experience and a review of the literature that amphotericin B
      bladder irrigations have any diagnostic or therapeutic value. The patient may be
      best served by removal of the urinary catheter, if possible, rather than by
      instillation of bladder irrigation with amphotericin B.

PMID- 15844070
TI  - Potential applications of conventional and molecular imaging to biodefense
      research.
AB  - Imaging methods that visualize the structure and function of the living body are
      widely used in patient care and biomedical research, but their full potential has
      not yet been applied to the study and treatment of the severe illnesses caused by
      pathogens of biodefense concern. "Conventional" imaging techniques (e.g.,
      radiography, computed tomography, ultrasound, or magnetic resonance imaging)
      delineate anatomic changes in tissues, whereas "molecular" methods employ
      magnetic resonance, positron emission tomography, single-photon emission computed
      tomography, or optical (fluorescence or bioluminescence) imaging to detect
      biochemical reactions that accompany pathogen replication or host responses. We
      review the basic principles of these methods, describe the diseases caused by 6
      pathogens classified as category A or B bioterror agents (anthrax, plague,
      tularemia, filoviral hemorrhagic fever, smallpox, and aerosolized equine
      encephalitis virus infection), and discuss how imaging could be used to study
      their pathogenesis in laboratory animals and to diagnose and monitor infection in
      humans.

PMID- 15844071
TI  - Association between acquired rifamycin resistance and the pharmacokinetics of
      rifabutin and isoniazid among patients with HIV and tuberculosis.
AB  - BACKGROUND: The occurrence of acquired rifamycin resistance despite use of
      directly observed therapy for tuberculosis is associated with advanced human
      immunodeficiency virus (HIV) disease and highly intermittent administration of
      antituberculosis drugs. Beyond these associations, the pathogenesis of acquired
      rifamycin resistance is unknown. METHODS: We performed a pharmacokinetic substudy
      of patients in a trial of treatment with twice-weekly rifabutin and isoniazid.
      RESULTS: A total of 102 (60%) of 169 patients in the treatment trial participated
      in the pharmacokinetic substudy, including 7 of 8 patients in whom tuberculosis
      treatment failure or relapse occurred in association with acquired rifamycin
      resistant mycobacteria (hereafter, "ARR failure or relapse"). The median
      rifabutin area under the concentration-time curve (AUC(0-24)) was lower for
      patients with than for patients without ARR failure or relapse (3.3 vs. 5.2
      microg*h/mL; P = .06, by the Mann-Whitney exact test). In a multivariate analysis
      adjusted for CD4+ T cell count, the mean rifabutin AUC(0-24) was significantly
      lower for patients with ARR failure or relapse than for other patients (3.0
      microg*h/mL [95% confidence interval {CI}, 1.9-4.5] vs. 5.2 microg*h/mL [95% CI,
      4.6-5.8]; P = .02, by analysis of covariance). The median isoniazid AUC(0-12) was
      not significantly associated with ARR failure or relapse (20.6 vs. 28.0
      microg*h/mL; P = .24, by the Mann-Whitney exact test). However, in a multivariate
      logistic regression model that adjusted for the rifabutin AUC(0-24), a lower
      isoniazid AUC(0-12) was associated with ARR failure or relapse (OR, 10.5; 95% CI,
      1.1-100; P = .04). CONCLUSIONS: Lower plasma concentrations of rifabutin and,
      perhaps, isoniazid were associated with ARR failure or relapse in patients with
      tuberculosis and HIV infection treated with twice-weekly therapy.

PMID- 15844072
TI  - Disorders of glucose metabolism among HIV-infected women.
AB  - BACKGROUND: Abnormal glucose metabolism in HIV-infected patients has largely been
      attributed to the use of protease inhibitors. However, most studies of glucose
      metabolism in HIV-infected patients have focused on men or have lacked
      appropriate control groups. METHODS: We assessed the factors associated with
      previously diagnosed diabetes among 620 middle-aged women with or at risk for HIV
      infection. For a subset of 221 women without previously diagnosed diabetes, we
      performed an oral glucose tolerance test (OGTT) to measure glucose and insulin
      levels, and we assessed factors associated with abnormal glucose tolerance,
      insulin resistance, and insulin secretion. RESULTS: Thirteen percent of the women
      in the present study had previously diagnosed diabetes. Among women without
      previously diagnosed diabetes who underwent an OGTT, 6% had previously
      undiagnosed diabetes, and 12% had impaired glucose tolerance (IGT). According to
      multivariate analysis, factors that were associated with previously diagnosed
      diabetes included current methadone treatment, body mass index of > or =25,
      family history of diabetes, and physical inactivity. Factors that were
      independently associated with an abnormal result of an OGTT (i.e., a result
      consistent with IGT or diabetes) included age > or =50 years, family history of
      diabetes, physical inactivity, and a high number of pack-years of smoking.
      Factors independently associated with insulin resistance included waist
      circumference, Hispanic ethnicity, physical inactivity, and, among HIV-infected
      women, use of HAART that did not include protease inhibitors. Factors associated
      with lower levels of insulin secretion included current opiate use (i.e.,
      methadone or heroin) and older age. CONCLUSIONS: Abnormal glucose metabolism is
      highly prevalent among middle-aged women with or at risk for HIV infection,
      particularly women who use opiates. Screening for diabetes in the HIV primary
      care setting should occur for women who have classic risk factors for diabetes,
      rather than solely for women who are taking PIs. Interventions that target
      modifiable risk factors, including obesity and physical inactivity, are also
      warranted.

PMID- 15844073
TI  - High rates of clinical and subclinical tuberculosis among HIV-infected ambulatory
      subjects in Tanzania.
AB  - BACKGROUND: We sought to determine the prevalence of active tuberculosis among
      ambulatory HIV-infected persons in Tanzania with CD4 cell counts of > or =200
      cells/mm3 and a bacille Calmette-Guerin vaccination scar. METHODS: Subjects who
      volunteered for a tuberculosis booster vaccine trial were screened for active
      tuberculosis by obtainment of a history, physical examination, chest radiography,
      sputum culture and acid fast bacillus (AFB) stain, and blood culture. All
      subjects underwent a tuberculin skin test (TST) and lymphocyte proliferation
      assays (LPAs) for detection of responses to mycobacterial antigens. RESULTS:
      Active tuberculosis was identified at baseline in 14 (15%) of the first 93
      subjects who were enrolled: 10 (71%) had clinical tuberculosis (symptoms or chest
      radiograph findings), and 4 (29%) had subclinical tuberculosis (positive sputum
      AFB stain or culture results but no symptoms or chest radiograph findings). An
      additional 6 subjects with subclinical tuberculosis were identified subsequently.
      The 10 subjects with subclinical tuberculosis included 3 with positive sputum AFB
      stains results and 7 who were only identified by a positive sputum culture
      result. Compared with subjects who did not have tuberculosis, the 10 subjects
      with subclinical tuberculosis were more likely to have peripheral
      lymphadenopathy, positive TST results, and elevated LPA responses to early
      secreted antigenic target-6 (ESAT). Eight of 10 patients had received isoniazid
      because of a positive TST result before active tuberculosis was recognized.
      CONCLUSIONS: Clinical and subclinical tuberculosis are common among ambulatory
      HIV-infected persons, and some cases can only be identified by sputum culture.
      World Health Organization guidelines for screening for latent tuberculosis before
      treatment do not recommend sputum culture and, therefore, may fail to identify a
      substantial number of HIV-infected persons with subclinical, active tuberculosis.

PMID- 15844074
TI  - Subclinical tuberculosis in HIV-infected patients: another challenge for the
      diagnosis of tuberculosis in high-burden countries?

PMID- 15844075
TI  - The impact of a 9-valent pneumococcal conjugate vaccine on the public health
      burden of pneumonia in HIV-infected and -uninfected children.
AB  - INTRODUCTION: Pneumococcal conjugate vaccine (PnCV) may be used as a probe to
      define the burden of pneumococcal disease and better characterize the clinical
      presentation of pneumococcal pneumonia. METHODS: This study used a 9-valent PnCV
      to define different end points of vaccine efficacy and the preventable burden of
      pneumococcal pneumonia in 39,836 children who were randomized in a double-blind,
      placebo-controlled trial in South Africa. RESULTS: Whereas the point-estimate of
      vaccine efficacy was greatest when measured against the outcome of vaccine
      serotype specific pneumococcal bacteremic pneumonia (61%; P = .01), the
      sensitivity of blood culture to measure the burden of pneumococcal pneumonia
      prevented by vaccination was only 2.6% in human immunodeficiency virus (HIV)
      uninfected children and 18.8% in HIV-infected children. Only 37.8% of cases of
      pneumococcal pneumonia prevented by PnCV were detected by means of chest
      radiographs showing alveolar consolidation. A clinical diagnosis of pneumonia
      provided the best estimate of the burden of pneumococcal pneumonia prevented
      through vaccination in HIV-uninfected children (267 cases prevented per 100,000
      child-years) and HIV-infected children (2573 cases prevented per 100,000 child
      years). CONCLUSION: Although outcome measures with high specificity, such as
      bacteremic pneumococcal pneumonia, provide a better estimate as to vaccine
      efficacy, the burden of disease prevented by vaccination is best evaluated using
      outcome measures with high sensitivity, such as a clinical diagnosis of
      pneumonia.

PMID- 15844076
TI  - Interpreting vaccine efficacy.

PMID- 15844077
TI  - Epstein-Barr virus infection-associated smooth-muscle tumors in patients with
      AIDS.
AB  - BACKGROUND: The aim of our study is to describe the unusual clinical
      manifestations of smooth-muscle tumors (SMTs) in patients with acquired
      immunodeficiency virus (AIDS) and to demonstrate the association between Epstein
      Barr virus (EBV) infection and SMTs. METHODS: Nine patients with AIDS and SMTs
      were characterized at Chulalongkorn Hospital (Bangkok, Thailand) from 2001
      through 2003. Tumor tissues suitable for immunohistochemical analysis and in situ
      hybridization were assayed for SMTs and EBV, respectively. Plasma and serum
      samples were tested for EBV by real-time quantitative polymerase chain reaction
      and serologic analysis. RESULTS: The study included 8 adults and 1 child (3 males
      and 6 females). All patients had CD4 cell counts of <200 cells/microL. By the end
      of the study, 3 patients had died, and 6 patients had survived. The sites of SMTs
      were the epidura (5 intracranial and 4 intraspinal SMTs), vocal cords (2),
      adrenal glands (2), abdominal wall (2), iris (1), liver (1), lung (1), orbit (1),
      and thigh (1). Seven patients had multicentric SMTs involving intracranial sites
      only (4 SMTs), extra- and intracranial sites (3), or extracranial sites only (2),
      which occurred either concurrently or sequentially. We found evidence of EBV
      infection, as determined by in situ hybridization, in all SMTs. Furthermore, EBV
      DNA was detectable in plasma samples from 2 patients. The results of serologic
      analysis were consistent with past EBV infection. CONCLUSIONS: SMTs in patients
      with AIDS typically arise in multiple and very unusual sites that are not often
      observed in SMTs among immunocompetent individuals. Our series also suggests
      association between EBV infection and SMTs in patients with AIDS. The exact role
      of EBV in smooth-muscle oncogenesis awaits further study.

PMID- 15844078
TI  - Risk factors for community-associated methicillin-resistant Staphylococcus aureus
      skin infections among HIV-positive men who have sex with men.
AB  - We investigated community-associated methicillin-resistant Staphylococcus aureus
      (CA-MRSA) skin infections among HIV-positive men who have sex with men. We
      performed a matched case-control study of 35 case patients and 76 control
      subjects. CA-MRSA skin infections were associated with high-risk sex and drug
      using behaviors and with environmental exposures but not with immune status.

PMID- 15844079
TI  - Prevalence of the ermB gene in Clostridium difficile strains isolated at a
      university teaching hospital from 1987 through 1998.
AB  - We analyzed 226 strains of Clostridium difficile for the presence of erythromycin
      ribosomal methylase B (ermB) genes. Forty-four strains (19.4%) carried ermB genes
      and were resistant to erythromycin. Toxin A and toxin B gene sequences were
      identified in 81.9% of these 44 strains. Strains of C. difficile that carry ermB
      genes are common etiologic agents of C. difficile-associated diarrhea.

PMID- 15844080
TI  - Quantification of adenovirus in the lower respiratory tract of patients without
      clinical adenovirus-related respiratory disease.
AB  - Adenovirus in bronchoalveolar lavage fluid samples from 50 patients without
      adenovirus-related illness was quantified. In 49 patients, adenovirus was found
      (median load, 3.3 x 10(3) copies/microg of DNA). The adenovirus load was
      inversely related to lymphocyte count (Pearson correlation coefficient r = 
      0.311; P = .03) and was significantly greater in immunosuppressed patients than
      in immunocompetent patients (5.1 x 10(3) vs. 2.0 x 10(3) copies/microg of DNA; P
      = .028).

PMID- 15844081
TI  - A case of Ramsay Hunt-like syndrome caused by herpes simplex virus type 2.
AB  - We report an immunocompetent patient with recurrent auricular and facial vesicles
      associated with painful paresthesias and facial paralysis, consistent with Ramsay
      Hunt syndrome, due to herpes simplex virus (HSV) type 2. Clinical and laboratory
      proven acyclovir resistance developed during therapy. Immunologic assays revealed
      normal reactivity to HSV-2.

PMID- 15844083
TI  - The clinical appearance of pinta mimics secondary syphilis: another trap of
      treponematosis?

PMID- 15844084
TI  - Patients with drug-resistant tuberculosis who were treated with standardized
      short-course chemotherapy.

PMID- 15844085
TI  - Ribavirin trials and hantavirus--what we should not conclude.

PMID- 15844086
TI  - Trimethoprim-sulfamethoxazole in the treatment of Stenotrophomonas maltophilia
      osteomyelitis.

PMID- 15844087
TI  - Improving the amplitude-modulated control experiment for multislice continuous
      arterial spin labeling.
AB  - The use of an amplitude-modulated radiofrequency (RF) pulse for a control
      experiment is a proven method to control for off-resonance effects in multislice
      continuous arterial spin labeling (CASL) experiments. This method is also known
      as double adiabatic inversion. The adiabaticity factor of a single half-pulse,
      beta(1/2), and a new dimensionless parameter alpha, which is obtained from the
      labeling parameters and the flow velocity, are introduced. This makes it possible
      to distinguish three distinct cases: 1) With low alpha, a double inversion
      occurs. 2) With alpha > or = approximately 4, the efficiency with which the
      longitudinal magnetization is returned to the z-axis depends on the phase of the
      amplitude modulation at the time the spins cross the center of the labeling
      plane. 3) In the intermediate region, the efficiency shows undesirable
      fluctuations. In a Bloch equation simulation, three optimized parameter sets are
      determined. Near ideal performance should always be achieved by combinations of
      parameters for which beta(1/2) > or = approximately 2 and alpha approximately
      pi/beta(1/2). The efficiency increases were realized in a volunteer study,
      showing the practical application of the suggested optimization.

PMID- 15844088
TI  - k-space correction of eddy-current-induced distortions in diffusion-weighted echo
      planar imaging.
AB  - This paper describes a method for correcting eddy-current (EC)-induced
      distortions in diffusion-weighted echo-planar imaging (DW-EPI). First, reference
      measurements of EC fields within the EPI acquisition window are performed for DW
      gradient pulses applied separately along each physical axis of the gradient set
      and for a range of gradient amplitudes. EC fields caused by the DW gradients of
      the DW-MRI protocol are then calculated using the reference EC measurements.
      Finally, these calculated fields are used to correct the respective DW-EPI raw (k
      space) data during image reconstruction. The technique was implemented in a small
      bore MRI scanner with no digital preemphasis. It corrected EC-induced image
      distortions in both phantom and in vivo brain diffusion tensor imaging (DTI) data
      more effectively than commonly used image-based techniques. The method did not
      increase imaging time, since the same reference EC measurements were used to
      correct data acquired from different phantoms, subjects, and DTI protocols.
      Because of the simplicity of the reference EC measurements, the method can easily
      be implemented in clinical scanners.

PMID- 15844089
TI  - Reduced field-of-view MRI with two-dimensional spatially-selective RF excitation
      and UNFOLD.
AB  - When the region of interest (ROI) is smaller than the object, one can increase
      MRI speed by reducing the imaging field of view (FOV). However, when such an
      approach is used, features outside the reduced FOV will alias into the reduced
      FOV image along the phase-encoding direction. Reduced-FOV methods are designed to
      correct this aliasing problem. In the present study, we propose a combination of
      two different approaches to reduce the acquired FOV: 1) two-dimensional (2D)
      spatially-selective RF excitation, and 2) the unaliasing by Fourier-encoding the
      overlaps using the temporal dimension (UNFOLD) technique. While 2D spatially
      selective RF excitation can restrict the spins excited within a reduced FOV, the
      UNFOLD technique can help to eliminate any residual aliased signals and thus
      relaxes the requirement for a long RF excitation pulse. This hybrid method was
      implemented for MR-based temperature mapping, and resulted in artifact-free
      images with a fourfold improvement in temporal resolution.

PMID- 15844090
TI  - Potassium transport in Langendorff-perfused mouse hearts assessed by 87Rb NMR
      spectroscopy.
AB  - We studied the fluxes of a potassium congener (Rb(+)) in mouse hearts by (87)Rb
      MRS at 8.4T. The hearts were loaded with Rb(+) by perfusion with Krebs-Henseleit
      buffer, in which 50% of K(+) was substituted with Rb(+). We initiated Rb(+)
      efflux by changing the perfusion medium to Rb(+)-free buffer. Spectra were
      acquired every 1.85 min, and the kinetics of Rb(+) transport were analyzed by
      means of monoexponential fits. The rate constants of Rb(+) uptake and efflux were
      0.0680 +/- 0.0028 and 0.0510 +/- 0.0051 min(-1), respectively (approximately 30%
      faster than in the rat heart). The ATP-sensitive potassium channel opener, P-1075
      (5 microM), and mitochondrial uncoupler, 2,4-dintrophenol (50 microM), activated
      Rb(+) efflux from mouse hearts by approximately 35%. The mechanisms responsible
      for the differences in Rb(+) uptake and efflux under baseline conditions and
      stimulation, in comparison with rat hearts, are discussed. These data provide a
      background for studies of cardiac potassium transport in transgenic mouse
      strains.

PMID- 15844091
TI  - Orientational dependence of intermolecular double quantum coherence (iDQC) signal
      from tendon tissue.
AB  - The proton signal changes as the long axis of tendon tissue is rotated with
      respect to the main magnetic field (B(0)). The orientational changes in the
      tendon signal obtained using the correlation spectroscopy revamped by asymmetric
      z-gradient echo detection (CRAZED) sequence, which allows the effects of
      intermolecular dipolar interactions to be observed, were investigated and
      compared with the orientational changes of the signals produced using correlation
      spectroscopy (COSY), spin-echo (SE), and one-pulse sequences. The intermolecular
      double quantum coherence (iDQC) signal obtained using the CRAZED sequence showed
      a variation in the signal from tendon tissue, with sharper peaks and greater
      relative differences between minimum and maximum signal values compared to the
      variations in the signal obtained from the COSY, SE, and one-pulse sequences.
      This result is attributed to the orientational dependence of the transverse
      relaxation rate of single (SQC) and double (DQH) quantum coherences R(2) and
      R(2,2), respectively.

PMID- 15844092
TI  - Optimized RF excitation for anatomical brain imaging of the occipital lobe using
      the 3D MDEFT sequence and a surface transmit coil.
AB  - An RF excitation scheme is presented for anatomical imaging of occipital brain
      areas at 3T using the 3D modified driven equilibrium Fourier transform (MDEFT)
      sequence and a transmit-receive surface coil. Surface coils operated in the
      transmit mode usually display a high B(1) inhomogeneity. This causes variations
      of the flip angle and impairs fat saturation, resulting in blurring, signal
      losses, and artifacts due to high scalp intensities. A composite binomial pulse
      with one spectral component for water selective excitation and one spatial
      component for B(1) inhomogeneity compensation is presented. It is shown
      experimentally that the pulse prevents image blurring and reduces the scalp
      signal considerably. The total pulse duration of only 2.4 ms is compatible with
      the relatively short repetition times (TRs) required for MDEFT imaging. The
      method is particularly useful for certain applications in neuroimaging that
      require technical equipment that is too large for standard coils or should not be
      exposed to RF fields.

PMID- 15844093
TI  - Itraconazole added to a lipid formulation of amphotericin B does not improve
      outcome of primary treatment of invasive aspergillosis.
AB  - BACKGROUND: Invasive aspergillosis (IA) is associated with poor outcome in
      patients with hematologic malignancy treated with amphotericin B (AMB)-based
      therapy. Itraconazole (ITC), a triazole with activity against Aspergillus, has
      been used in combination with AMB or lipid formulations of AMB (LipoAMB) in the
      treatment of IA, although the efficacy of this strategy is uncertain. METHODS: To
      determine whether the addition of ITC to LipoAMB improves outcome of IA, the
      authors retrospectively studied 179 consecutive patients with hematologic
      malignancies and definite or probable IA who received primary antifungal therapy
      with either LipoAMB (n = 146), or lipoAMB plus ITC (n = 33) between June 1993 and
      June 2003. In view of the erratic absorption of ITC tablets, only patients who
      received either intravenous or liquid ITC were analyzed. Patients who received <
      1 week of treatment were excluded. RESULTS: Evaluable patients in both groups
      (LipoAMB: n =101; ITC and LipoAMB: n = 11) had comparable distribution of risk
      factors of poor outcome such as neutropenia at onset of IA, persistent
      neutropenia, systemic steroids, previous antifungal prophylaxis, admission to the
      intensive care unit, disseminated IA, previous bone marrow transplant, and IA due
      to infection by a non-fumigatus Aspergillus species. Response to primary
      antifungal therapy was equally poor in both groups (LipoAMB group: 10%; ITC and
      LipoAMB group: 0%; P = not significant). CONCLUSIONS: In the authors' 10-year
      study of patients with hematologic malignancy and IA, the response rate to
      LipoAMB given as primary therapy was very poor. In a comparable group of
      patients, the addition of ITC did not result in a therapeutic benefit.

PMID- 15844094
TI  - Theoretical noise model for oxygenation-sensitive magnetic resonance imaging.
AB  - Contrast-to-noise ratio (CNR) in blood oxygenation level-dependent (BOLD) based
      functional MRI (fMRI) studies is a fundamental parameter to determine statistical
      significance and therefore to map functional activation in the brain. The CNR is
      defined here as BOLD contrast with respect to temporal fluctuation. In this
      study, a theoretical noise model based on oxygenation-sensitive MRI signal
      formation is proposed. No matter what the noise sources may be in the signal
      acquired by a gradient-echo echo-planar imaging pulse sequence, there are only
      three noise elements: apparent spin density fluctuations, S(0)(t); transverse
      relaxation rate fluctuations, R(2) (*)(t); and thermal noise, n(t). The noise
      contributions from S(0)(t), R(2) (*)(t), and n(t) to voxel time course
      fluctuations were evaluated as a function of echo time (TE) at 3 T. Both noise
      contributions caused by S(0)(t) and R(2) (*)(t) are significantly larger than
      that of thermal noise when TE = 30 ms. In addition, the fluctuations between
      S(0)(t) and R(2) (*)(t) are cross-correlated and become a noise factor that is
      large enough and cannot be ignored. The experimentally measured TE dependences of
      noise, temporal signal-to-noise ratio, and BOLD CNR in finger-tapping activation
      regions were consistent with the proposed model. Furthermore, the proposed
      theoretical models not only unified previously proposed BOLD CNR models, but also
      provided mechanisms for interpreting apparent controversies and limitations that
      exist in the literature.

PMID- 15844095
TI  - Splanchnic (visceral) mesoderm has limb-forming ability according to the position
      along the rostrocaudal axis in chick embryos.
AB  - Positioning of the limb is one of the important events for limb development. In
      the early stage of embryogenesis, the lateral plate mesoderm splits into two
      layers and the dorsal layer (the somatic mesoderm) gives rise to a series of
      distinct structures along the rostrocaudal axis, including the forelimb bud,
      flank body wall, and hindlimb bud. To determine whether positional information in
      the somatic mesoderm for regionalization along the rostrocaudal axis is also
      inherited by the ventral layer of the lateral plate mesoderm (the splanchnic
      mesoderm), experiments in which the splanchnic mesoderm was transplanted under
      the ectoderm in an in ovo chick system were carried out. Transplantation of the
      wing-, flank-, and leg-level splanchnic mesoderm resulted in the formation of
      wings, nothing, and legs, respectively. These results suggest that the splanchnic
      mesoderm possesses the ability to form limbs and that the ability differs
      according to the position along the rostrocaudal axis. The position-specific
      ability to form limbs suggests that there are some domains involved in the
      formation of position-specific structures in the digestive tract derived from the
      splanchnic mesoderm, and results of cell fate tracing supported this possibility.
      In contrast, analysis of shh expression suggested that the anteroposterior
      polarity in the limb region seems not to be inherited by the splanchnic mesoderm.
      We propose that the positioning of limb buds is specified and determined in the
      very early stage of development of the lateral plate mesoderm before splitting
      and that the polarity in a limb bud is established after the splitting of the
      mesoderm.

PMID- 15844096
TI  - Expression of Xenopus XlSALL4 during limb development and regeneration.
AB  - The multi-C2H2 zinc-finger domain containing transcriptional regulators of the
      spalt (SAL) family plays important developmental regulatory roles. In a
      competitive subtractive hybridization screen of genes expressed in Xenopus laevis
      hindlimb regeneration blastemas, we identified a SAL family member that, by
      phylogenetic analysis, falls in the same clade as human SALL4 and have designated
      it as XlSALL4. Mutations of human SALL4 have been linked to Okihiro syndrome,
      which includes preaxial (anterior) limb defects. The expression pattern of
      XlSALL4 transcripts during normal forelimb and hindlimb development and during
      hindlimb regeneration at the regeneration-competent and regeneration-incompetent
      stages is temporally and regionally dynamic. We show for the first time that a
      SAL family member (XlSALL4) is expressed at the right place and time to play a
      role regulating both digit identity along the anterior/posterior axis and
      epimorphic limb regeneration.

PMID- 15844098
TI  - Sef is synexpressed with FGFs during chick embryogenesis and its expression is
      differentially regulated by FGFs in the developing limb.
AB  - The signaling pathways leading to growth and patterning of various organs are
      tightly controlled during the development of any organism. These control
      mechanisms usually involve the utilization of feedback- and pathway-specific
      antagonists where the pathway induces the expression of its own antagonist. Sef
      is a feedback antagonist of fibroblast growth factor (FGF) signaling, which has
      been identified recently in zebrafish and mammals. Here, we report the isolation
      of chicken Sef (cSef) and demonstrate the conserved nature of the regulatory
      relationship with FGF signaling. In chick embryos, Sef is expressed in a pattern
      that coincides with many known sites of FGF signaling. In the developing limb,
      cSef is expressed in the mesoderm underlying the apical ectodermal ridge (AER) in
      the region known as the progress zone. cSef message first appeared after limb
      budding and AER formation. Expression was intense at stages of rapid limb
      outgrowth, and gradually decreased to almost undetectable levels when
      differentiation was clearly apparent. Gain- and loss-of-function experiments
      showed that FGFs differentially regulate the expression of cSef in various
      tissues. Thus, removal of the AER down-regulated cSef expression, and FGF2 but
      not FGF4 or FGF8 beads substituted for the AER in maintaining cSef expression. At
      sites where cSef is not normally expressed, FGF4 and FGF2, but not FGF8 beads,
      induced cSef expression. Our results demonstrate the complexity of cSef
      regulation by FGFs and point to FGF2 as a prime candidate in regulating cSef
      expression during normal limb development. The spatiotemporal pattern of cSef
      expression during limb development suggests a role for cSef in regulating limb
      outgrowth but not limb initiation.

PMID- 15844099
TI  - Zac1 is expressed in progenitor/stem cells of the neuroectoderm and mesoderm
      during embryogenesis: differential phenotype of the Zac1-expressing cells during
      development.
AB  - Zac1, a new zinc-finger protein that regulates both apoptosis and cell cycle
      arrest, is abundantly expressed in many neuroepithelia during early brain
      development. In the present work, we study the expression of Zac1 during early
      embryogenesis and we determine the cellular phenotype of the Zac1-expressing
      cells throughout development. Our results show that Zac1 is expressed in the
      progenitor/stem cells of several tissues (nervous system, skeleton, and skeletal
      muscle), because they colocalize with several progenitor/stem markers (Nestin,
      glial fibrillary acidic protein, FORSE-1, proliferating cell nuclear antigen, and
      bromodeoxyuridine). In postnatal development, Zac1 is expressed in all phases of
      the life cycle of the chondrocytes (from proliferation to apoptosis), in some
      limbic gamma-aminobutyric acid-ergic neuronal subpopulations, and during
      developmental myofibers. Therefore, the intense expression of Zac1 in the
      progenitor/stem cells of different cellular lineages during the proliferative
      cycle, before differentiation into postmitotic cells, suggests that Zac1 plays an
      important role in the control of cell fate during neurogenesis, chondrogenesis,
      and myogenesis.

PMID- 15844100
TI  - Function of the mammalian postorbital bar.
AB  - Complete postorbital bars, bony arches that encompass the lateral aspect of the
      eye and form part of a circular orbit, have evolved homoplastically multiple
      times during mammalian evolution. Numerous functional hypotheses have been
      advanced for postorbital bars, the most promising being that postorbital bars
      function to stiffen the lateral orbit in taxa that have significant angular
      deviation between the temporal fossa and the bony orbit. Without a stiff lateral
      orbit the anterior temporalis muscle and fascia potentially would pull on the
      postorbital ligament, deform the orbit, and cause disruption of oculomotor
      precision. Morphometric data were collected on 1,329 specimens of 324 taxa from
      16 orders of extant eutherian and metatherian mammals in order to test whether
      the orientation of the orbit relative to the temporal fossa is correlated with
      the replacement of the postorbital ligament with bone. The allometric and
      ecological influences on orbit orientation across mammals are also explored. The
      morphometric results corroborate the hypothesis: Shifts in orbit orientation
      relative to the temporal fossa are correlated with the size of the postorbital
      processes, which replace the ligament. The allometric and ecological factors that
      influence orbit orientation vary across taxa. Postorbital bars stiffen the
      lateral orbital wall. Muscle pulleys, ligaments, and other connective tissue
      attach to the lateral orbital wall, including the postorbital bar. Without a
      stiff lateral orbit, deformation due to temporalis contraction would displace
      soft tissues contributing to normal oculomotor function.

PMID- 15844101
TI  - Molecular organization and signal transduction at intermembrane junctions.
AB  - Surfaces create an environment in which multiple forces conspire together to
      yield a wealth of complex chemical processes. This is especially true of cell
      membranes, whose fluidity and flexibility enables responsive feedback with
      surface chemical interactions in ways not generally seen with inorganic
      materials. Spatial pattern formation of cell-surface proteins at intermembrane
      junctions provides many beautiful examples of these phenomena, and is also
      emerging as a functional aspect of intercellular signaling. Correspondingly, the
      study of interactions of cell-membrane surfaces is attracting significant
      attention from cell biologists and physical chemists alike. This convergence is
      fueled be recent, exquisite observations of protein pattern formation events
      within living immunological synapses along with parallel advances in membrane
      reconstitution, manipulation, and imaging technologies.

PMID- 15844102
TI  - Intermolecular tandem Pd-catalyzed cross-coupling/[4+4] and [4+2] cycloadditions:
      a one-pot, five-component assembly of bicyclo[6.4.0]dodecanes.

PMID- 15844103
TI  - A new minimal surface and the structure of mesoporous silicas.

PMID- 15844104
TI  - The geometric and electronic structure of [(cyclam-acetato)Fe(N)]+: a genuine
      iron(v) species with a ground-state spin S = 1/2.

PMID- 15844105
TI  - Local structure and anisotropic backbone dynamics from cross-correlated NMR
      relaxation in proteins.

PMID- 15844106
TI  - Rare-earth oxide nanopolyhedra, nanoplates, and nanodisks.

PMID- 15844107
TI  - Synthesis and solid-state structure of a metal complex of a diphosphineimine.

PMID- 15844108
TI  - Real-time membrane fission of giant polymer vesicles.

PMID- 15844109
TI  - Reversible self-organization of semisynthetic zinc chlorins into well-defined rod
      antennae.

PMID- 15844110
TI  - Infrared, UV/Vis, and W-band EPR spectroscopic characterization and
      photochemistry of triplet mesitylphosphinidene.

PMID- 15844111
TI  - Highly enantioselective organocatalytic hydroxyalkylation of indoles with ethyl
      trifluoropyruvate.

PMID- 15844112
TI  - "On water": unique reactivity of organic compounds in aqueous suspension.

PMID- 15844113
TI  - Gas-filled polyelectrolyte capsules.

PMID- 15844114
TI  - Tuning a metal's oxidation state: the potential of clathrochelate systems.

PMID- 15844115
TI  - Iodine-assisted assembly of helical coordination polymers of cucurbituril and
      asymmetric copper(II) complexes.

PMID- 15844116
TI  - Dimetallic dioxygen activation leading to a doubly oxygen-bridged dirhodium
      complex.

PMID- 15844117
TI  - Supramolecular features of calixarene-based synthetic nanotubes.

PMID- 15844118
TI  - Stereoselective Lewis acid mediated [1,3] ring contraction of 2,5-dihydrooxepins
      as a route to polysubstituted cyclopentenes.

PMID- 15844119
TI  - Preparation of enolate-homoenolate species as (Z)-gamma-siloxyallylmetal
      equivalents: sequential 1,4-addition of bis(iodozincio)methane to 1,4
      dicarbonylbutenes and cyclopropanation.

PMID- 15844120
TI  - Ditopic complexation and release of neutral guest molecules by a hydrogen-bonded
      "endo-exo" receptor.

PMID- 15844121
TI  - Solvent effect on crystal polymorphism: why addition of methanol or ethanol to
      aqueous solutions induces the precipitation of the least stable beta form of
      glycine.

PMID- 15844122
TI  - DNA-based asymmetric catalysis.

PMID- 15844123
TI  - Concise and practical synthesis of latrunculin a by ring-closing enyne-yne
      metathesis.

PMID- 15844124
TI  - Self-assembled diamide nanotubes in organic solvents.

PMID- 15844125
TI  - Total synthesis of (+)-dactylolide through an efficient sequential Peterson
      olefination and Prins cyclization reaction.

PMID- 15844126
TI  - Subvalent compounds featuring direct metal-metal bonds: the Zn-Zn bond in
      [Cp*2Zn2].

PMID- 15844127
TI  - V-shaped molecules: new contenders for the biaxial nematic phase.

PMID- 15844128
TI  - Study of the segmental dynamics in semi-crystalline poly(lactic acid) using
      mechanical spectroscopies.
AB  - The glass transition of poly(L-lactic acid) (PLLA) occurs not far above typical
      service temperatures (room or body temperatures) which has consequences on the
      material properties during its use, such as damping or the occurrence of
      structural relaxation. This work aims at characterising the glass transition
      dynamics of a semi-crystalline PLLA using both dynamic mechanical analysis (DMA)
      and thermally stimulated recovery (TSR). The main viscoelastic parameters have
      been characterised at 1 Hz using DMA and the master curve obtained after
      isothermal experiments at different temperatures provided a full picture of the
      solid-state rheological behaviour throughout a wide frequency range. The
      activation energies calculated from the shift factors agree with the TSR ones,
      exhibiting a maximum near the T(g). Above the T(g), the results can be described
      with the WLF model. In the glassy state, the activation energy decreases with
      decreasing temperatures being always higher than the prediction of the Adam and
      Gibbs theory, at least down to temperatures 30 degrees C below the T(g). This
      suggests the existence of non-arrested degrees of freedom in the glassy state,
      being consistent with the existence of a significant degree of cooperativity in
      the TSR results.

PMID- 15844129
TI  - Improving polylactide/starch biocomposites by grafting polylactide with acrylic
      acid--characterization and biodegradability assessment.
AB  - In this article, the properties of a polylactide and starch composite
      (PLA/starch) and an acrylic acid grafted polylactide and starch composite (PLA-g
      AA/starch) were compared. The composite containing PLA-g-AA was found to have
      much better dispersion and homogeneity of starch in the polymer matrix than the
      composite containing PLA, indicating better compatibility between the two phases.
      Better mechanical and thermal properties of the PLA-g-AA/starch composite,
      notably an increase in tensile strength and elongation at breakpoint, evidenced
      its superiority to the PLA/starch composite. Furthermore, the lower viscosity of
      PLA-g-AA/starch makes it easier to process than PLA/starch. Weight loss on
      exposure to a soil environment over a period of three months showed that the
      starch in the composites was almost completely biodegradable, even at a high
      degree of substitution (60 wt.-% starch). After three months in soil, a reduction
      in the mechanical properties of the blends was observed, especially in those with
      higher starch contents.

PMID- 15844130
TI  - Maleimido-terminated self-assembled monolayers.
AB  - Four approaches have been explored for the preparation of maleimido
      functionalized self-assembled monolayers (SAMs) on silicon. SAMs prepared by self
      assembly of maleimido-functionalized alkyltrichlorosilanes (11-maleimido-undecyl
      trichlorosilane) on oxide-covered silicon yield higher signals from maleimido
      functionalities in ATR-IR (attenuated total reflection IR) spectroscopy and XPS
      (X-ray photoelectron spectroscopy) than the other three methods. The surface
      composition of maleimido groups was tailored further by the formation of mixed
      monolayers with nonfunctionalized alkyltrichlorosilanes (decyltrichlorosilane).
      The order of the alkyl chains within the monolayers only slightly depends on the
      composition of the mixed monolayers. We utilized the maleimido-terminated SAMs to
      bind various nucleophilic compounds, alkylamines, alkylthiols, and thiol-tagged
      DNA oligonucleotides by means of conjugate addition.

PMID- 15844131
TI  - Polyoxometalate monolayers in Langmuir-Blodgett films.
AB  - Langmuir and Langmuir-Blodgett (LB) films of a variety of polyoxometalates of
      different shapes, sizes, and charges were prepared by taking advantage of the
      adsorption properties of these polyanions on a positively charged monolayer of an
      organic surfactant spread on water. Three different aspects were investigated. 1)
      The electrochemical and electrochromic properties of LB films containing the
      easily reducible polyoxoanion [P2Mo18O62]6-. Absorbance changes of these LB films
      deposited onto an ITO substrate have been induced by repeated switching of the
      applied potential. These changes are due to the formation of the colored reduced
      forms of the polyanion. Coloration and bleaching of the LB film occur very
      quickly and are reversible. 2) The preparation of LB films based on magnetic
      polyoxometalates, such as the Keggin anions, [CoW12O40]6- and [SiMn(OH2)W11O39]6
      , or containing magnetic clusters of increasing nuclearities such as
      [Co4(H2O)2(PW9O34)2]10- and [Co4(H2O)2(P2W15O62)2]16- based on a Co4O16
      ferromagnetic cluster, and the polyoxometalates
      [Co9(OH)3(H2O)6(HPO4)2(PW9O34)3]16- and [Ni9(OH)3-(H2O)6(HPO4)2(PW9O34)3]16-
      based on a nonanuclear M9O36 cluster. 3) The preparation of LB films of the giant
      heteropolyoxomolybdate, [Na3(NH4)12][Mo57Fe6(NO)6O174(OH)3-(H2O)24]76 H2O.

PMID- 15844132
TI  - Supramolecular microcontact printing and dip-pen nanolithography on molecular
      printboards.
AB  - The transfer of functional molecules onto self-assembled monolayers (SAMs) by
      means of soft and scanning-probe lithographic techniques-microcontact printing
      (muCP) and dip-pen nanolithography (DPN), respectively-and the stability of the
      molecular patterns during competitive rinsing conditions were examined. A series
      of guests with different valencies were transferred onto beta-cyclodextrin- (beta
      CD-) terminated SAMs and onto reference hydroxy-terminated SAMs. Although
      physical contact was sufficient to generate patterns on both types of SAMs, only
      molecular patterns of multivalent guests transferred onto the beta-CD SAMs were
      stable under the rinsing conditions that caused the removal of the same guests
      from the reference SAMs. The formation of kinetically stable molecular patterns
      by supramolecular DPN with a lateral resolution of 60 nm exemplifies the use of
      beta-CD-terminated SAMs as molecular printboards for the selective immobilization
      of printboard-compatible guests on the nanometer scale through the use of
      specific, multivalent supramolecular interactions. Electroless deposition of
      copper on the printboard was shown to occur selectively on the areas patterned
      with dendrimer-stabilized gold nanoparticles.

PMID- 15844133
TI  - Synthesis and modification of terrylenediimides as high-performance fluorescent
      dyes.
AB  - Two new synthetic approaches to terrylenediimides, highly photostable fluorescent
      dyes, are described. For the first time terrylenediimide has been synthesised in
      a straightforward procedure that makes large quantities available. The second
      route includes an efficient cross-coupling reaction followed by a
      cyclodehydrogenation. Monofunctionalisation of the imide structure allows
      terrylenediimides now to be coupled with a variety of compounds, for example, by
      Suzuki cross-coupling, which can lead to an array of terrylenediimides with new
      functional groups such as hydroxy, amino, or carboxy groups needed to link up
      with other molecules. The functionalisation in the bay region is used to tune the
      properties of terrylenediimides and extend the range of applications, for
      example, by introducing water solubility. These tetrasubstituted
      terrylenediimides offer, depending on the substituents used, exciting features
      such as good solubility in common organic solvents, water solubility, or NIR
      absorption.

PMID- 15844134
TI  - Self-assembled structure in room-temperature ionic liquids.
AB  - Self-assembled vesicles, structurally equivalent to some hydrotropes, have been
      obtained from a Zn2+-fluorous surfactant or in the mixture of Zn2+-fluorous
      surfactant/zwitterionic surfactant in room-temperature ionic liquids (RTILs). The
      existence of bilayers arranged in vesicles in RTILs would be very exciting, open
      several new possibilities as reaction media, and increase our understanding of
      the physical and chemical factors for self-assembling systems in RTILs.

PMID- 15844135
TI  - Synthesis, structural features, absorption spectra, redox behaviour and
      luminescence properties of ruthenium(ii) rack-type dinuclear complexes with
      ditopic, hydrazone-based ligands.
AB  - The isomeric bis(tridentate) hydrazone ligand strands 1 a-c react with
      [Ru(terpy)Cl3] (terpy=2,2':6',2''-terpyridine) to give dinuclear rack-type
      compounds 2 a-c, which were characterised by several techniques, including X-ray
      crystallography and NMR methods. The absorption spectra, redox behaviour and
      luminescence properties (both in fluid solution at room temperature and in rigid
      matrix at 77 K) of the ligand strands 1 a-c and of the metal complexes 2 a-c have
      been studied. Compounds 1 a-c exhibit absorption spectra dominated by intense pi
      pi* bands, which, in the case of 1 b and 1 c, extend within the visible region,
      while the absorption spectra of the rack-type complexes 2 a-c show intense bands
      both the in the UV region, due to spin-allowed ligand-centred (LC) transitions,
      and in the visible, due to spin-allowed metal-to-ligand charge-transfer (MLCT)
      transitions. The energy position of these bands strongly depends on the ligand
      strand: in the case of 2 a, the lowest energy MLCT band is around 470 nm, while
      in 2 b and 2 c, it lies beyond 600 nm. Ligands 1 a-c undergo oxidation processes
      that involve orbitals based mainly on the CH3--N--N== fragments. The complexes 2
      a-c undergo reversible metal-centred oxidation, while reductions involve the
      hydrazone-based ligands: in 2 b and 2 c, the bridging ligand is reduced twice and
      in 2 a once before reduction of the peripheral terpy ligands takes place. Ligands
      1 a-c exhibit luminescence from the lowest-lying 1pi-pi* level. Only for complex
      2 a does emission occur; this may be attributed to a 3MLCT state involving the
      bridging ligand. Taken together, the results clearly indicate that the structural
      variations introduced translate into interesting differences in the
      spectroscopic, luminescence and redox properties of the ligand strands as well as
      of the rack-type metal complexes.

PMID- 15844136
TI  - An electrophilic cleavage procedure for the asymmetric dihydroxylation: direct
      enantioselective synthesis of cyclic boronic esters from olefins.
AB  - A variation within the osmium-catalysed asymmetric dihydroxylation (AD) of
      olefins is described that yields cyclic boronic esters from olefins in a straight
      forward manner. This process represents the first real product alteration in
      asymmetric dihydroxylation, since all previous protocols lead to free diols
      exclusively. A protocol based on the Sharpless AD conditions (for
      enantioselective oxidation of prochiral olefins) was developed that gives cyclic
      boronic esters with excellent enantiomeric excesses (ee's). Some of the ee's are
      higher than those reported for conventional AD. The unprecedented role of phenyl
      boronic acid on the course of the AD reaction was investigated in detail.
      PhB(OH)2 does not interfere with the chiral ligand, leaving the enantioselective
      step of olefin oxidation intact. The main role of the boronic acids-apart from
      protecting the diol products against potential overoxidation-relies on removing
      the diol entity in an electrophilic cleavage, which is in contrast to the
      conventional hydrolytic cleavage of the AD protocols. Thus, a mechanistically new
      cleavage for enantioselective dihydroxylation reactions is introduced within the
      present work.

PMID- 15844137
TI  - Active-passive gradient shielding for MRI acoustic noise reduction.
AB  - An important source of MRI acoustic noise-magnet cryostat warm-bore vibrations
      caused by eddy-current-induced forces-can be mitigated by a passive metal shield
      mounted on the outside of a vibration-isolated, vacuum-enclosed shielded gradient
      set. Finite-element (FE) calculations for a z-gradient indicate that a 2-mm-thick
      Cu layer wrapped on the gradient assembly can decrease mechanical power
      deposition in the warm bore and reduce warm-bore acoustic noise production by
      about 25 dB. Eliminating the conducting warm bore and other magnet parts as
      significant acoustic noise sources could lead to the development of truly quiet,
      fully functioning MRI systems with noise levels below 70 dB.

PMID- 15844138
TI  - Black blood gradient echo cine magnetic resonance imaging of the mouse heart.
AB  - A black blood gradient echo sequence for multiphase cardiac MRI of the mouse
      heart was implemented on a 4.7-T scanner and compared to a conventional bright
      blood sequence. Black blood was achieved using the double inversion recovery
      technique. Ten mice were imaged using both the bright and the black blood
      sequences, and 2 of the mice were additionally imaged using bright and black
      blood sequences modified to perform myocardial tagging. Manual planimetry of the
      images was performed by two independent observers to detect the endocardial and
      epicardial borders and subsequently to compute chamber volumes and myocardial
      mass. Weight of the excised left ventricle was used as a gold standard for
      myocardial mass. Bland-Altman analysis demonstrated reduced interobserver
      variability for the measurement of cardiac volumes using the black blood sequence
      compared to the bright blood sequence (95% confidence interval was -0.89-0.73
      microL for black blood versus -1.86-1.28 microL for bright blood). Also, Bland
      Altman analysis showed that the black blood sequence provides improved accuracy
      for the measurement of myocardial mass compared to the bright blood sequence
      (average difference between MRI versus weight was 0.9 microg for black blood and 
      11.2 microg for bright blood, P < 0.01). For myocardial tagging, qualitative
      assessment demonstrated improved endocardial border definition using the black
      blood sequence. Black blood cine MRI in mice provides reduced interobserver
      variability and improved accuracy for the measurement of myocardial volumes and
      mass compared to the conventional bright blood technique.

PMID- 15844139
TI  - In vivo EPR spectroscopic imaging for a liposomal drug delivery system.
AB  - We used the membrane-impermeable nitroxyl radical 4-trimethylammonium-2,2,6,6
      tetramethylpiperidine-1-oxyliodide (CAT-1) as a model drug encapsulated in
      liposomes in order to separately map the 2D distribution of both liposomal
      encapsulated CAT-1 and free CAT-1. Phantoms were prepared with a CAT-1 solution
      and a liposomal CAT-1 suspension. Spectral-spatial images were obtained along
      several polar-arranged spatial axes through the phantom. The 1D spatial
      distributions (projections) of each signal component, reflecting the
      concentration of CAT-1, were then extracted from the spectral-spatial images. 2D
      EPR images of liposomal-encapsulated CAT-1 and free CAT-1 were separately
      reconstructed from the resulting projection data sets. 2D mapping of each
      component exhibited good agreement with respect to the phantom. Separate maps
      were generated from separate injections of free CAT-1 and liposomal CAT-1
      injected into the femoral muscle of a living mouse. The EPR signal of the free
      CAT-1 gradually decreased during data acquisition. Because of this decay, we
      calibrated the image intensity by extrapolating the signal intensity to that
      detected at the beginning of data sampling. Both the position and size of the
      individual images were in very good agreement with those of the mouse thigh
      obtained by MRI.

PMID- 15844140
TI  - Imaging of single human carcinoma cells in vitro using a clinical whole-body
      magnetic resonance scanner at 3.0 T.
AB  - The purpose of the present study was to examine whether single human carcinoma
      cells labeled with iron oxide nanoparticles could be detected by magnetic
      resonance (MR) imaging on a clinical 3-T scanner using a surface coil only. WiDr
      human colon carcinoma cells were loaded with two kinds of iron oxide
      nanoparticles differing by coating and size: aminosilan-coated (MagForce) and
      carboxy-dextran-coated particles (Resovist). The latter were preferred by the
      colon carcinoma cell line used here and taken up much faster (12 h) than the
      smaller carboxydextran-coated Resovist (48 h). Labeled single carcinoma cells,
      distributed in an agarose gel in a monodisperse layer as controlled by light
      microscopy, became detectable as punctuate signal extinctions when using a small
      circularly polarized surface coil in conjunction with a T(2)*-weighted GE
      sequence at 3 T. The threshold for the detectability of labeled colon carcinoma
      cells ranged at a load of 4-5 mug iron/10(6) cells. Obviating the need for
      special hardware additions, this study opens a new lane for single-cell tracking
      on clinical 3-T MR scanners amenable to patient studies.

PMID- 15844141
TI  - Free-breathing renal magnetic resonance angiography with steady-state free
      precession and slab-selective spin inversion combined with radial k-space
      sampling and water-selective excitation.
AB  - The impact of radial k-space sampling and water-selective excitation on a novel
      navigator-gated cardiac-triggered slab-selective inversion prepared 3D steady
      state free-precession (SSFP) renal MR angiography (MRA) sequence was
      investigated. Renal MRA was performed on a 1.5-T MR system using three inversion
      prepared SSFP approaches: Cartesian (TR/TE: 5.7/2.8 ms, FA: 85 degrees), radial
      (TR/TE: 5.5/2.7 ms, FA: 85 degrees) SSFP, and radial SSFP combined with water
      selective excitation (TR/TE: 9.9/4.9 ms, FA: 85 degrees). Radial data acquisition
      lead to significantly reduced motion artifacts (P < 0.05). SNR and CNR were best
      using Cartesian SSFP (P < 0.05). Vessel sharpness and vessel length were
      comparable in all sequences. The addition of a water-selective excitation could
      not improve image quality. In conclusion, radial k-space sampling reduces motion
      artifacts significantly in slab-selective inversion prepared renal MRA, while SNR
      and CNR are decreased. The addition of water-selective excitation could not
      improve the lower CNR in radial scanning.

PMID- 15844142
TI  - Positive contrast magnetic resonance imaging of cells labeled with magnetic
      nanoparticles.
AB  - Contrast agents incorporating superparamagnetic iron-oxide nanoparticles have
      shown promise as a means to visualize labeled cells using MRI. Labeled cells
      cause significant signal dephasing due to the magnetic field inhomogeneity
      induced in water molecules near the cell. With the resulting signal void as the
      means for detection, the particles behave as a negative contrast agent, which can
      suffer from partial-volume effects. In this paper, a new method is described for
      imaging labeled cells with positive contrast. Spectrally selective RF pulses are
      used to excite and refocus the off-resonance water surrounding the labeled cells
      so that only the fluid and tissue immediately adjacent to the labeled cells are
      visible in the image. Phantom, in vitro, and in vivo experiments show the
      feasibility of the new method. A significant linear correlation (r = 0.87, P <
      0.005) between the estimated number of cells and the signal was observed.

PMID- 15844143
TI  - In vivo prostate magnetic resonance spectroscopic imaging using two-dimensional J
      resolved PRESS at 3 T.
AB  - In vivo magnetic resonance spectroscopic imaging of the prostate using single
      voxel and multivoxel two-dimensional (2D) J-resolved sequences is investigated at
      a main magnetic field strength of 3 T. Citrate, an important metabolite often
      used to aid the detection of prostate cancer in magnetic resonance spectroscopic
      exams, can be reliably detected along with the other metabolites using this
      method. We show simulations and measurements of the citrate metabolite using 2D J
      resolved spectroscopy to characterize the spectral pattern. Furthermore, using
      spiral readout gradients, the single-voxel 2D J-resolved method is extended to
      provide the spatial distribution information as well all within a reasonable scan
      time (17 min). Phantom and in vivo data are presented to illustrate the
      multivoxel 2D J-resolved spiral chemical shift imaging sequence.

PMID- 15844144
TI  - Quantitative shear wave magnetic resonance elastography: comparison to a dynamic
      shear material test.
AB  - Magnetic resonance elastography (MRE), a phase contrast MRI technique, images the
      propagation of applied mechanical waves in tissue, allowing shear stiffness to be
      quantified in vivo. This MRE technique has been validated with static mechanical
      compression tests. Dynamic mechanical analysis (DMA) may be a more appropriate
      comparison to MRE because it directly measures the shear modulus dynamically,
      while compression tests convert the measured elastic modulus to shear modulus
      with an assumed Poisson ratio. This study compared the shear stiffness estimated
      with various MRE inversion algorithms (i.e., manual calculation, local frequency
      estimate, phase gradient, direct inversion, and matched filter) to the dynamic
      mechanical test. The shear stiffness of five agarose gels with concentrations
      ranging from 1.5 to 3.5% were measured using MRE and DMA. The phase gradient
      inversion algorithm overestimated the shear modulus at higher concentrations
      (i.e., 3-3.5% agar), while the results from the other techniques correlated well
      with the dynamic mechanical test.

PMID- 15844145
TI  - Optimizing spherical navigator echoes for three-dimensional rigid-body motion
      detection.
AB  - Spherical navigator (SNAV) echoes show promise in correcting for three
      dimensional rigid-body motion. In this paper, several important parameters in the
      design and performance of the SNAV technique are discussed, including a novel
      sampling strategy, the optimal k-space radius and sampling density of the
      navigator, and the execution of the SNAV trajectory by the scanner hardware. A
      variable-sampling density (VSD) helical-spiral SNAV trajectory, which can acquire
      data on the entire spherical shell without exceeding the maximum slew rate of the
      scanner, is presented. To ensure that the VSD SNAV trajectory was properly
      executed by the scanner hardware, the gradient waveforms were verified using a
      self-encoding technique. The ability of the VSD SNAV to measure rotational and
      translational motion was studied with in vitro experiments at various k-space
      radii and sampling densities. The results of this study show that the best
      accuracy was attained at k-space radii of 1.4 and 1.6 cm(-1), with 2400 to 4000
      samples acquired over the sphere.

PMID- 15844146
TI  - Reliability estimation of grouped functional imaging data using penalized maximum
      likelihood.
AB  - We analyzed grouped fMRI data and developed a reliability analysis for such data
      using the method of penalized maximum likelihood (ML). Specifically, this
      technique was applied to a somatosensory paradigm that used a mechanical probe to
      provide noxious stimuli to the foot, and a paradigm consisting of four levels of
      graded peripheral neuromuscular electrical stimulation (NMES). In each case,
      reliability maps of activation were generated. Receiver operating characteristic
      (ROC) curves were constructed in the case of the graded NMES paradigm for each
      level of stimulation, which revealed an increase in the specificity of activation
      with increasing stimulation levels. In addition, penalized ML was used to
      determine whether the grouped reliability maps obtained from one stimulus level
      were significantly different from those obtained at other levels. The results
      show a significant difference (P < 0.01) in the reliability of activation from
      one stimulation level to the next. These results are in agreement with those
      obtained using generalized linear modeling (GLM). While the reliability maps
      generated are not directly comparable, they are qualitatively similar to those
      obtained by controlling the expected false discovery rate (FDR). The proposed
      methodology can be used to objectively compare activation maps between groups, as
      well as to perform reliability assessments. Furthermore, this method potentially
      can be used to assess the longitudinal effect of treatment therapies within a
      group.

PMID- 15844147
TI  - Sequence design for magnetic resonance spectroscopic imaging of prostate cancer
      at 3 T.
AB  - Magnetic resonance spectroscopic imaging (MRSI) has proven to be a powerful tool
      for the metabolic characterization of prostate cancer in patients before and
      following therapy. The metabolites that are of particular interest are citrate
      and choline because an increased choline-to-citrate ratio can be used as a marker
      for cancer. High-field systems offer the advantage of improved spectral
      resolution as well as increased magnetization. Initial attempts at extending MRSI
      methods to 3 T have been confounded by the J-modulation of the citrate
      resonances. A new pulse sequence is presented that controls the J-modulation of
      citrate at 3 T such that citrate is upright, with high amplitude, at a practical
      echo time. The design of short (14 ms) spectral-spatial refocusing pulses and
      trains of nonselective refocusing pulses are described. Phantom studies and
      simulations showed that upright citrate with negligible sidebands is observed at
      an echo time of 85 ms. Studies in a human subject verified that this behavior is
      reproduced in vivo and demonstrated that the water and lipid suppression of the
      new pulse sequence are sufficient for application in prostate cancer patients.

PMID- 15844148
TI  - 3D volume-localized pO2 measurement in the human lung with 3He MRI.
AB  - A method for 3D volume-localized quantification of pO2 in the lungs is presented
      that uses repetitive frame 3D gradient-echo imaging of (3)He. The method was
      demonstrated by experiments on (3)He phantoms containing known concentrations of
      O(2) and in vivo on a group of three healthy human volunteers. The results were
      compared with those obtained by equivalent 2D thin-slice and 2D projection
      methodologies, and were found to be consistent with published results from the 2D
      projection methodologies (pO(2) = 0.09-0.18 bar). Studies performed on the same
      subject, on three separate occasions, demonstrated a repeatability of pO(2)
      measurement to within 14% using the 3D technique. Experimental differences
      between the 2D and 3D methods were substantiated with theoretical and numerical
      analyses of the signal decay, which took into account the effects of out-of-slice
      diffusion as a source of error in the thin-slice 2D experiments. It is shown that
      the 2D thin-slice technique systematically underestimates pO2 when there is
      significant gas diffusion (factor of 4 underestimate for D = 0.9 cm(2)s(-1)
      representative of free (3)He in air).

PMID- 15844149
TI  - Confidence mapping in diffusion tensor magnetic resonance imaging tractography
      using a bootstrap approach.
AB  - The bootstrap technique is an extremely powerful nonparametric statistical
      procedure for determining the uncertainty in a given statistic. However, its use
      in diffusion tensor MRI tractography remains virtually unexplored. This work
      shows how the bootstrap can be used to assign confidence to results obtained with
      deterministic tracking algorithms. By invoking the concept of a "tract
      propagator," it also underlines the important effect of local fiber architecture
      or architectural milieu on tracking reproducibility. Finally, the practical
      advantages and limitations of the technique are discussed. Not only does the
      bootstrap allow any deterministic tractography algorithm to be used in a
      probabilistic fashion, but also its model-free inclusion of all sources of
      variability (including those that cannot be modeled) means that it provides the
      most realistic approach to probabilistic tractography.

PMID- 15844150
TI  - Trace apparent diffusion coefficients of metabolites in human brain using
      diffusion weighted magnetic resonance spectroscopy.
AB  - The rotationally invariant trace/3 apparent diffusion coefficients (ADC) of N
      acetyl aspartate (NAA), creatine and phosphocreatine (tCr), and choline (Cho)
      were determined using a diffusion-weighted stimulated echo acquisition mode
      sequence at 3 T in three separate human brain regions, namely the subcortical
      white matter, occipital gray matter, and frontal gray matter. The measurement of
      the mean diffusivity eliminates the dependence of the measured ADC on the
      direction of the diffusion gradient relative to the tissue microstructure (i.e.,
      anisotropy). Macroscopic brain motions induce phase errors that were compensated
      for by phasing (zero and first order) on the single average spectrum (zero order
      on the NAA peak) prior to summing the individual spectra. This method yielded
      reproducible trace/3 ADC values in the expected range without the use of cardiac
      gating. The mean diffusivity of NAA (0.14 +/- 0.03 x 10(-3) mm(2)/s) appears to
      be less than that of tCr (0.17 +/- 0.04 x 10(-3) mm(2)/s) and Cho (0.18 +/- 0.05
      x 10(-3) mm(2)/s) in human brain.

PMID- 15844151
TI  - Accurate myocardial T1 measurements: toward quantification of myocardial blood
      flow with arterial spin labeling.
AB  - In this study, we investigated a method for accurately measuring myocardial T(1)
      for the quantification of myocardial blood flow (MBF) with arterial spin labeling
      (ASL). A single-shot gradient-echo (GE)-based ASL sequence with an adiabatic
      hyperbolic secant inversion recovery pulse was modified to acquire a pair of
      myocardial T(1)'s within a breath-hold. A multivariable regression algorithm that
      accounted for the magnetization saturation effects was developed to calculate
      T(1). The MBF was then determined with a well-developed model. The accuracy of
      our T(1) calculation was first evaluated in a phantom, and then in six dogs for
      the MBF calculation, with (N = 4) and without (N = 2) coronary artery stenosis.
      In the phantom study, the accuracy of T(1) measured with a slice-selective
      inversion prepared pulse was within 2.5% of error. In healthy dogs, the MBF
      increased 2-5 times during vasodilation. In contrast, regional differences of MBF
      were well visualized in the stenotic dogs during vasodilation (perfusion reserve
      of 2.75 +/- 0.83 in normal myocardium, and 1.46 +/- 0.75 in the stenotic area). A
      correlation analysis revealed a close agreement in MBF between the ASL and
      microsphere (MS) in both healthy and stenotic dogs. In summary, the modified ASL
      technique and T(1) regression algorithm proposed here provide an accurate
      measurement of myocardial T(1) and demonstrate potential for reliably assessing
      MBF at steady state.

PMID- 15844152
TI  - Higher-order harmonic transmission-line RF coil design for MR applications.
AB  - A novel concept based on the use of higher-order harmonic resonances in a
      transmission-line resonator is introduced for the design of high-frequency RF
      coils at high and ultrahigh fields, where conventional RF coil designs present
      difficulties and limitations. To demonstrate this concept, we successfully
      designed and fabricated a 400-MHz RF coil for rat imaging using a second-harmonic
      resonant microstrip transmission line. This coil has a high Q-factor, reduces
      coil-cable interactions without the use of a matching balun, and has a broad
      range for tuning the coil's resonant frequency at the loaded condition. This work
      demonstrates that the use of higher-order harmonics in a transmission-line
      resonator provides an alternative, efficient approach to the design of large and
      high-frequency RF coils.

PMID- 15844153
TI  - Simultaneous perfusion and blood-oxygenation-level-dependent measurements using
      single-shot interleaved z-shim echo-planar imaging.
AB  - Single-shot interleaved z-shim EPI (SSIZS-EPI) was extended to a simultaneous
      perfusion and blood-oxygenation-level-dependent (BOLD) imaging technique that
      reduces susceptibility-induced signal loss while preserving rapid image
      acquisition. Experiments on human brains showed that images acquired with this
      technique had improved signal-to-noise ratio in the inferior prefrontal, meso-,
      and lateral-temporal lobes compared with a conventional EPI. Perfusion maps
      obtained from the SSIZS-EPI images at resting state illustrated substantial
      signal recovery in these brain areas. Perfusion and BOLD images collected with a
      sensorimotor paradigm demonstrated the feasibility of the technique to
      simultaneously measure cerebral blood flow and blood oxygenation signals
      associated with brain activation. Functional experiments with a neuropsychiatric
      paradigm showed increased brain activities in the periamygdalar regions in both
      perfusion and BOLD maps, consistent with a previous H(2) (15)O PET study. The
      proposed technique, with its advantages of reducing susceptibility artifacts and
      fast scanning speed, would be useful for obtaining more reliable measurements of
      functional signals, particularly in the brain regions with field inhomogeneities.

PMID- 15844154
TI  - Quantification of resting myocardial blood flow in a pig model of acute ischemia
      based on first-pass MRI.
AB  - Qualitative and semiquantitative contrast-enhanced (CE) dynamic perfusion MRI
      techniques are established as noninvasive diagnostic means of assessing coronary
      artery disease. However, to date quantification of myocardial blood flow (MBF)
      has not reached the same acceptance as MBF quantification with nuclear
      techniques. To validate quantification of MBF at rest using the extracellular
      contrast agent (CA) Gd-DTPA, we performed an animal study in a pig model of acute
      myocardial ischemia. We quantified MBF from MRI data with a mathematical model
      (MMID4) of the underlying vasculature. These MBF results were subsequently
      compared with the results from fluorescent microspheres. The study showed a
      correlation of r = 0.66 between MBF estimates obtained with MRI and those
      obtained with fluorescent microspheres. The correlation for ischemic and
      nonischemic myocardium was r = 0.86 and r = 0.47, respectively. In conclusion,
      quantification of resting MBF using MMID4 is a valid method under conditions of
      acute myocardial ischemia.

PMID- 15844155
TI  - Oxygen-enhanced proton imaging of the human lung using T2.
AB  - Magnetic susceptibility gradients caused by tissue/air interfaces lead to very
      short T(2)* times in the human lung. These susceptibility gradients are dependent
      on the magnetic susceptibility of the respiratory gas and therefore should
      influence T(2)* relaxation. In this work, a technique for quantitative T(2)*
      mapping of the human lung during one breath hold is presented. Using this method,
      the lung T(2)* relaxation time was measured under normoxic (room air, 21% O(2))
      and hyperoxic (100% O(2)) conditions to verify this assumption. The mean T(2)*
      difference between room air and 100% O(2) is about 10% and contains ventilation
      information, since only ventilated regions contribute to signal change due to
      different susceptibility gradients.

PMID- 15844156
TI  - Limits of detection of SPIO at 3.0 T using T2 relaxometry.
AB  - T(2)* relaxometry for quantitative MR imaging is strongly hampered by large-scale
      field inhomogeneities, which lead to signal losses and an overestimation of the
      relaxation rate R(2)*. This is of particular importance for the sensitive
      detection of iron oxide contrast agent distributions. To derive an accurate
      measurement of T(2)*, a main field inhomogeneity correction is applied: the main
      field inhomogeneity is derived from multislice T(2)* relaxometry data and used as
      an initial value for an iterative optimization, by which the relaxation signal is
      corrected for each voxel. These corrected T(2)* maps show reduced influence of
      the local field variation and contain information about the local SPIO
      concentration. The method was tested on phantoms and the limit of detection of
      SPIO labeled cells using T(2)* relaxometry was estimated in volunteers to be 120
      x 10(3) cells/mL (2.4 microg Fe/mL) in the brain and 385 x 10(3) cells/mL (8
      microg Fe/mL) in the liver.

PMID- 15844157
TI  - RESTORE: robust estimation of tensors by outlier rejection.
AB  - Signal variability in diffusion weighted imaging (DWI) is influenced by both
      thermal noise and spatially and temporally varying artifacts such as subject
      motion and cardiac pulsation. In this paper, the effects of DWI artifacts on
      estimated tensor values, such as trace and fractional anisotropy, are analyzed
      using Monte Carlo simulations. A novel approach for robust diffusion tensor
      estimation, called RESTORE (for robust estimation of tensors by outlier
      rejection), is proposed. This method uses iteratively reweighted least-squares
      regression to identify potential outliers and subsequently exclude them. Results
      from both simulated and clinical diffusion data sets indicate that the RESTORE
      method improves tensor estimation compared to the commonly used linear and
      nonlinear least-squares tensor fitting methods and a recently proposed method
      based on the Geman-McClure M-estimator. The RESTORE method could potentially
      remove the need for cardiac gating in DWI acquisitions and should be applicable
      to other MR imaging techniques that use univariate or multivariate regression to
      fit MRI data to a model.

PMID- 15844158
TI  - Accelerating MRI by skipped phase encoding and edge deghosting (SPEED).
AB  - A fast imaging method called skipped phase encoding and edge deghosting (SPEED)
      is introduced. The k-space is sparsely sampled into three interleaved datasets,
      each with a skip-size N and a relative shift in phase encoding (PE). These
      datasets are separately reconstructed by 2DFT and edge-enhanced by a differential
      filter in the PE direction, resulting in edge maps with phase-shifted aliasing
      ghosts. The sparseness of edges reduces the chance of ghost overlapping. Typical
      ghosted-edge maps can be adequately modeled with only two dominating ghost layers
      that are resolved from a set of three equations using least-square error
      minimization, yielding N ghost maps of different orders that can be registered
      and averaged into a single deghosted-edge map for noise and artifact reduction.
      Finally, the deghosted-edge map is transformed into a deghosted image by an
      inverse filter. A few central k-space lines are collected without PE skip to aid
      the inverse filtering. SPEED has been demonstrated by in vivo data to reduce scan
      time considerably without noticeable artifacts. It has various potential
      applications, such as MR angiography (MRA), where the signal itself is sparse. As
      an independent method, SPEED can be combined with other fast imaging methods for
      further acceleration.

PMID- 15844159
TI  - Sodium ion apparent diffusion coefficient in living rat brain.
AB  - The apparent diffusion coefficient (ADC) of Na(+) was determined in live rat
      brain. The brain extracellular-to-intracellular Na(+) content ratio is
      approximately 8:2, which is the inverse of that for water in these spaces.
      Consequently, the ADC of Na(+) is primarily affected by motion in the
      extracellular space, and Na(+) can be viewed as a reporter molecule for motion in
      that space. Likewise, water ADC is dominated by intracellular motion. The brain
      Na(+) ADC was 1.15 +/- 0.09 microm(2)/ms, which is 61% of the aqueous Na(+) free
      diffusion coefficient (D(free)) at 37 degrees C (1.9 microm(2)/ms), while the ADC
      for brain water is 28% of the water D(free) at 37 degrees C (3 microm(2)/ms).
      This suggests that the ADC of molecular species within the extracellular space is
      roughly twofold that within the intracellular space. In postmortem brain, both
      Na(+) and water decrease to 17% of the respective D(free) values. These results
      are consistent with Na(+) and water ADC values sharing the same biophysical
      determinants in postmortem brain. The observed difference between Na(+) and water
      ADC/D(free) ratios in living brain tissue may be attributable to the
      extracellular environment hindering molecular displacements twofold less than the
      intracellular environment.

PMID- 15844160
TI  - Imaging articular cartilage under compression--cartilage elastography.
AB  - We constructed a device to compress small samples of articular cartilage while
      the samples were imaged in a 1.5 T imager. With the use of a piezoelectric
      piston, the device compressed 1-cm-diameter cylindrical samples of articular
      cartilage (200 microm) at a rate of 2 Hz. Simultaneously, we imaged the samples
      with a displacement-sensitive stimulated-echo acquisition mode (STEAM) sequence.
      We validated the technique using tissue that mimicked silicone samples. We
      compared the results from the same cartilage samples before and after they were
      degraded by digestion in trypsin. The extent of degradation was visualized from
      T(1)-weighted images of the samples after they were soaked in 0.5 mmolar of
      GdDTPA. The resulting elastographic images show compression and differential
      strain in directions both parallel and perpendicular to the surface of the
      cartilage. The static elastographic images that depict compression made before
      digestion and after 5 and 15 hr of trypsin digestion show that the elastic
      modulus of the samples decreased with a spatial variation consistent with the
      enzymatic digestion as revealed by the T(1) images. We believe this technique
      will be useful in studies of the mechanical properties of articular cartilage and
      other tissues, and may in the future be extended to the clinical setting.

PMID- 15844161
TI  - An adjustable adiabatic pulse for selective population inversion.
AB  - A new adiabatic inversion pulse and its design principles are presented. An
      analytical expression in the pulse length, inversion bandwidth, inversion
      efficiency, peak RF amplitude, and width of the transition region is derived and
      validated. Accordingly, the pulse shape can be adapted to achieve a specified
      inversion performance. Adjusted for broadband application, population can be
      inverted band selectively, rather independently of spatial RF field
      inhomogeneities, and with significantly reduced peak RF amplitude in comparison
      with the well-known hyperbolic secant adiabatic pulse.

PMID- 15844162
TI  - Continuous artery-selective spin labeling (CASSL).
AB  - A new technique for selective spin labeling of individual arteries is presented.
      It is based on continuous arterial spin labeling (CASL) with an amplitude
      modulated control experiment. Precessionary motion of the labeling gradient about
      the axis of the artery, combined with an appropriate frequency modulation of the
      labeling RF pulse, restricts the adiabatic inversion to the desired artery. In
      phantom studies, it was found that the level of selectivity could be controlled
      by the sequence parameters, and that the achievable labeling efficiency was at a
      level of approximately 80% compared to a regular, nonselective CASL experiment.
      In a volunteer study we acquired high-quality images of the perfusion territories
      of the internal carotid artery (ICA), the basilar artery (BA), the middle
      cerebral artery (MCA), and both anterior cerebral arteries (ACAs). The results
      show the method's flexibility for different geometries and flow velocities.
      Potential applications include perfusion territory imaging of smaller cerebral
      arteries, and selective angiography techniques.

PMID- 15844163
TI  - High-resolution diffusion tensor imaging of human patellar cartilage: feasibility
      and preliminary findings.
AB  - MR diffusion tensor imaging (DTI) was used to analyze the microstructural
      properties of articular cartilage. Human patellar cartilage-on-bone samples were
      imaged at 9.4T using a diffusion-weighted SE sequence (12 gradient directions,
      resolution = 39 x 78 x 1500 microm(3)). Voxel-based maps of the mean diffusivity,
      fractional anisotropy (FA), and eigenvectors were calculated. The mean
      diffusivity decreased from the surface (1.45 x 10(-3) mm(2)/s) to the tide mark
      (0.68 x 10(-3) mm(2)/s). The FA was low (0.04-0.28) and had local maxima near the
      surface and in the portion of the cartilage corresponding to the radial layer.
      The eigenvector corresponding to the largest eigenvalue showed a distinct zonal
      pattern, being oriented tangentially and radially in the upper and lower portions
      of the cartilage, respectively. The findings correspond to current scanning
      electron microscopy (SEM) data on the zonal architecture of cartilage. The
      eigenvector maps appear to reflect the alignment of the collagenous fibers in
      cartilage. In view of current efforts to develop and evaluate structure-modifying
      therapeutic approaches in osteoarthritis (OA), DTI may offer a tool to assess the
      structural properties of cartilage.

PMID- 15844164
TI  - Metabolic characterization of distinct neuroanatomical regions in rats by magic
      angle spinning 1H nuclear magnetic resonance spectroscopy.
AB  - High-resolution magic angle spinning (HRMAS) (1)H NMR spectroscopy has been
      applied to the biochemical characterization of specific brain regions in rats in
      order to establish baseline levels of tissue metabolite profiles with which to
      compare models of neuropathology or toxic lesion. Cores of tissue (20 mg) from
      the brain stem, cerebellum, frontal cortex, and hippocampus were obtained from
      histologically defined coronal slices of brain from 18 male Sprague-Dawley rats.
      HRMAS (1)H NMR spectra were acquired for each of the regions sampled and the
      degree of intersample variability, as assessed by principal components analysis
      and discriminant analysis by projection to latent structure was found to be low.
      Clear region-specific differences in the biochemical profiles were observed using
      both comparison of metabolite ratios and/or pattern recognition methods.
      Relatively low concentrations of GABA in the cerebellum, high concentrations of
      taurine and N-acetylaspartate in the cortex, and high levels of choline,
      glycerophosphocholine, and phosphocholine in the hippocampus predominantly
      influenced the classification of the different brain regions. Additionally, N
      acetylaspartylglutamate was detected in the brain stem, but was largely absent
      from the other regions examined. Such analyses provide a baseline reference for
      further HRMAS NMR spectroscopic studies to monitor disease and pharmacological
      insults in specific regions of the brain.

PMID- 15844165
TI  - Hexagonal zero mode TEM coil: a single-channel coil design for imaging multiple
      small animals.
AB  - A novel hexagonal coil design for simultaneous imaging of multiple small animals
      is presented. The design is based on a coaxial cavity and utilizes the magnetic
      field formed between two coaxial conductors with hexagonal cross-sections. An
      analytical solution describing the B(1) field between conductors of the hexagonal
      coil was found from the Biot-Savart law. Both experimental results and analytical
      calculations showed a variation in the B(1) field within the imaging region of
      less than 10%. Numerical calculations predicted approximately 35% improvement in
      B(1) field homogeneity with the hexagonal coil design compared to a cylindrical
      coaxial cavity design. The experimentally-measured signal-to-noise ratio (SNR) of
      the hexagonal coil loaded with six 50-mM phantoms was only 4-5% lower than that
      of a single parallel plate resonator loaded with one phantom. In vivo spin-echo
      (SE) images of six 7-day-old rat pups acquired simultaneously demonstrated
      sufficient SNR for microimaging. The construction scheme of the coil, simple
      methods for tuning and matching, and an anesthesia device and animal holder
      designed for the coil are described. The hexagonal coil design utilizes a single
      receiver and allows for simultaneous imaging of six small animals with no
      significant compromise in SNR.

PMID- 15844166
TI  - Optimized 1H MRS and MRSI methods for the in vivo detection of
      boronophenylalanine.
AB  - Boronophenylalanine (BPA) is used as Boron-10 carrier in boron neutron capture
      therapy, an experimental cancer radiotherapy. Results of quantitative,
      noninvasive in vivo detection and imaging of BPA in laboratory animals using (1)H
      NMR are presented for the first time. The purpose of this study was to implement
      and validate optimized techniques for the efficient detection of BPA. The (1)H
      NMR signals through which BPA is most readily detected in vivo are those from the
      aromatic ring of the molecule, which are part of a scalar-coupled spin system.
      The preferred detection method should therefore be based on a pulse sequence in
      which the effective TE is as short as possible. Modified versions of LASER
      (tau(CP) = 4.6 ms, TE = 27.6 ms) and double-echo slice-selective 2D MRSI (TE = 12
      ms) were implemented for single-voxel spectroscopy and spectroscopic imaging of
      BPA, respectively. Chemical shift selective excitation was used for both
      sequences, based on a pulse that enabled narrow-band excitation without
      concomitant delay in TE. SI data without water suppression was used for absolute
      quantitation and for correction of B(0) variations. Experiments were conducted at
      4.7 T in phantoms and in mice where the infused BPA was detected in the kidney.

PMID- 15844167
TI  - Retroactive, a membrane-anchored extracellular protein related to vertebrate
      snake neurotoxin-like proteins, is required for cuticle organization in the larva
      of Drosophila melanogaster.
AB  - Mutations in the rtv gene cause disarrangement of chitin fibers in the cuticle of
      the Drosophila larva, and occasionally the cuticle detaches from the epidermis.
      We have identified the rtv gene, and using the new HHpred homology detection
      method, we show that the Rtv protein defines a new family of disulfide-rich
      proteins in insects that are related to vertebrate snake neurotoxin-like
      proteins, including CD59 and transforming growth factor-beta type II receptors.
      Rtv is an extracellular membrane-anchored protein exposing six aromatic residues
      that may mediate binding to chitin. We propose that this binding function of Rtv
      may assist the organization of chitin fibers at the epidermal cell surface during
      cuticle assembly.

PMID- 15844168
TI  - Distribution of the limbic system-associated membrane protein (LAMP) in pigeon
      forebrain and midbrain.
AB  - The limbic system-associated membrane protein (LAMP) is an adhesion molecule
      involved in specifying regional identity during development, and it is enriched
      in the neuropil of limbic brain regions in mammals but also found in some somatic
      structures. Although originally identified in rat, LAMP is present in diverse
      species, including avians. In this study, we used immunolabeling with a
      monoclonal antibody against rat LAMP to examine the distribution of LAMP in
      pigeon forebrain and midbrain. LAMP immunolabeling was prominent in many
      telencephalic regions previously noted as limbic in birds. These regions include
      the hippocampal complex, the medial nidopallium, and the ventromedial
      arcopallium. Subpallial targets of these pallial regions were also enriched in
      LAMP, such as the medial-most medial striatum. Whereas some telencephalic areas
      that have not been regarded as limbic were also LAMP-rich (e.g., the hyperpallium
      intercalatum and densocellulare of the Wulst, the mesopallium, and the
      intrapeduncular nucleus), most nonlimbic telencephalic areas were LAMP-poor
      (e.g., field L, the lateral nidopallium, and somatic basal ganglia). Similarly,
      in the diencephalon and midbrain, prominent LAMP labeling was observed in such
      limbic areas as the dorsomedial thalamus, the hypothalamus, the ventral tegmental
      area, and the central midbrain gray, as well as in a few nonlimbic areas such as
      nucleus rotundus, the shell of the nucleus pretectalis, the superficial tectum,
      and the parvocellular isthmic nucleus. Thus, as in mammals, LAMP in birds appears
      to be enriched in most known forebrain and midbrain limbic structures but is
      present as well in some somatic structures.

PMID- 15844169
TI  - Spatiotemporal localization of the calcium-stimulated adenylate cyclases, AC1 and
      AC8, during mouse brain development.
AB  - Type 1 and type 8 adenylate cyclases, AC1 and AC8, are membrane bound enzymes
      that produce cAMP in response to calcium entry and could thus control a large
      number of developmental processes. We provide a detailed spatiotemporal
      localization of these genes in the mouse brain during embryonic and postnatal
      life using in situ hybridization. AC1 gene expression begins early in embryonic
      life (before E13), and its expression is much more widespread than in adults.
      Transient expression of AC1 is found in the striatum, the dorsal thalamus, the
      trigeminal nerve nuclei, the Purkinje cells of the cerebellum, the interneurons
      of the hippocampus, and the retinal ganglion cells. In all these structures, the
      peak of AC1 gene expression occurs during early postnatal life, decreasing by
      P10. After P15, AC1 expression is confined to the hippocampus, the cerebral
      cortex, and to the granule cells of the cerebellum. AC8 gene expression also
      begins early in embryonic life (E12)--but in a more limited number of regions
      than in adults. AC8 expression is initially restricted to the epithalamus, the
      hypothalamus, the superior colliculus, the cerebellar anlage the proliferative
      zone of the rhombic lip, and the spinal cord. The expression increases and
      broadens during postnatal life, particularly in the thalamus and the cerebral
      cortex. A transient peak of AC8 expression is found in layer IV of the
      somatosensory cortex. Thus, AC1 and AC8 have an early developmental onset with
      complementary spatiotemporal distribution patterns: AC1 is most broadly
      distributed in embryonic life, whereas AC8 is most broadly expressed in
      adulthood. Transient expression of these genes designate areas that may be
      particularly sensitive to neural activity/calcium-modulated cAMP responses during
      development.

PMID- 15844170
TI  - Integrin activation and neurotrophin signaling cooperate to enhance neurite
      outgrowth in sensory neurons.
AB  - Neurite growth is influenced by many factors, including the availability of
      trophic support as well as the extracellular environment. In this study, we have
      investigated whether attachment to a permissive culture substrate such as laminin
      is sufficient to promote neurite outgrowth from dorsal root ganglion neurons in
      the absence of added nerve growth factor (NGF) and whether this attachment can
      enhance the response of these neurons to NGF. Adult dorsal root ganglia neurons
      plated on surfaces coated with a thin film of laminin exhibited increased neurite
      outgrowth. This effect was integrin-dependent as it was attenuated by treatment
      with RGD (arginine-glycine-aspartate) peptides and by a beta1-integrin blocking
      antibody. The addition of NGF resulted in a significant increase in the integrin
      dependent outgrowth. We have correlated this increase in growth with increased
      expression of integrin subunits and activation of known downstream signaling
      intermediates such as focal adhesion kinase, Src, and Akt. We have also examined
      pathway cooperation through the use of an Src-specific inhibitor, PP2, and a
      beta1-integrin blocking antibody, beta1i, by observing downstream signaling
      intermediates in both integrin and growth factor signaling pathways. These
      results are among the first to detail the importance of interactions between
      neurotrophin- and integrin-activated signaling in adult primary neurons.

PMID- 15844171
TI  - Projections of male-specific receptor neurons in the antennal lobe of the
      Oriental tobacco budworm moth, Helicoverpa assulta: a unique glomerular
      organization among related species.
AB  - The macroglomerular complex in the primary olfactory center of male moths
      receives information from numerous pheromone-detecting receptor neurons housed in
      specific sensilla located on the antennae. We investigated the functional
      organization of the three glomeruli constituting this complex in Helicoverpa
      assulta, a unique species among heliothine moths as concerns the composition of
      the pheromone blend. By tip recordings from the male-specific receptor neurons
      combined with cobalt-lysine stainings, the axon terminals in the brain were
      traced and subsequently reconstructed by camera lucida drawings. Some were also
      reconstructed in a digital form. The results showed that the sensilla could be
      classified into two functional types. A major category housed two colocalized
      receptor neurons, one responding to the primary pheromone component cis-9
      hexadecenal and the other to the behavioral antagonists cis-9-tetradecenal and
      cis-9-hexadecenol. Cobalt-lysine applied to this sensillum type consistently
      resulted in two stained axons, each terminating in one of the two large subunits
      of the macroglomerular complex: the cumulus or the dorsomedial glomerulus. The
      second, less frequently appearing sensillum type contained a receptor neuron
      responding to the second pheromone component, cis-11-hexadecenal. Dye applied to
      this type resulted in stained axon projections in the ventral glomerulus. In an
      evolutionary context it is particularly interesting that differences of related
      heliothine species are reflected in the functional organization of the MGC
      compartments.

PMID- 15844172
TI  - Citrullination of central nervous system proteins during the development of
      experimental autoimmune encephalomyelitis.
AB  - Immunization of mammals with central nervous system (CNS)-derived proteins or
      peptides induces experimental autoimmune encephalomyelitis (EAE), a disease
      resembling the human autoimmune disease multiple sclerosis (MS). Both diseases
      are accompanied by destruction of a part of the of the myelin sheaths, which
      surround neurites in the CNS. Previous studies in MS have described alterations
      in the citrullination of myelin basic protein, one of the main protein
      constituents of the myelin sheath. Here, we show that, also during the
      development of EAE in mice, hypercitrullination occurs in the areas of the spinal
      cord that show the highest degree of inflammation and that myelin basic protein
      and glial fibrillary acidic protein are among the hypercitrullinated proteins. We
      conclude that hypercitrullination of myelin proteins in the CNS is a common
      phenomenon in demyelinating disease. Hypercitrullination may cause conformational
      changes in proteins, so the affected proteins may be involved in the pathogenesis
      of CNS autoimmune disease by acting as autoreactive T-cell epitopes. This is the
      first report in which hypercitrullination of CNS proteins in EAE is described and
      in which proteins other than myelin basic protein are reported to be
      citrullinated during autoimmune-mediated CNS inflammation.

PMID- 15844173
TI  - Expression of citrullinated proteins in murine experimental autoimmune
      encephalomyelitis.
AB  - In this study, we demonstrate for the first time the immunohistochemical
      expression of citrullinated proteins in the central nervous system (CNS) of mice
      with myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune
      encephalomyelitis (EAE). By using an established monoclonal antibody (F95)
      against natural and synthetic citrullinated proteins (Nicholas and Whitaker
      [2002] Glia 37:328-336), numerous, small, previously unrecognized "patches" of
      citrullinated proteins were discovered throughout EAE brains, whereas EAE spinal
      cords showed similar but much larger lesions. On dual color immunofluorescence,
      these lesions were found to contain citrullinated myelin basic protein (MBP) and
      were surrounded by astrocytes immunoreactive for both glial fibrillary acidic
      protein (GFAP) and F95. These lesions became evident about the time when EAE mice
      became symptomatic and increased in size and number with increasing disease
      severity. In some sections of spinal cord but not brains of severely debilitated
      EAE mice, a widespread gliotic response was seen, with astrocytes containing
      citrullinated GFAP spread throughout the gray and white matter. Western blot
      analysis of acidic proteins from the brains and spinal cords of EAE mice had
      higher levels of multiple citrullinated GFAP isoforms compared with controls,
      with more F95-positive bands in the EAE brains vs. spinal cords. These results
      raise the possibility that citrullination of both GFAP and MBP may contribute to
      the pathophysiology of EAE and that the brains of EAE mice may contain more
      pathology than previously realized.

PMID- 15844174
TI  - High incidence of disease recurrence in the brain and leptomeninges in patients
      with nonsmall cell lung carcinoma after response to gefitinib.
AB  - BACKGROUND: Gefitinib is an epidermal growth factor receptor tyrosine kinase
      inhibitor that induces an early and dramatic response in 10% of patients with
      advanced nonsmall cell lung carcinoma (NSCLC). Long- term outcome and patterns of
      disease recurrence after response have not been described. METHODS: The authors
      evaluated 139 patients with NSCLC treated with gefitinib at Memorial Sloan
      Kettering Cancer Center (New York, NY) between 1998 and 2002. They focused on
      patterns of disease recurrence, risk of brain metastases (BM) and leptomeningeal
      metastasis (LM), and long-term outcome after initial response to gefitinib.
      RESULTS: Of the 139 patients treated with gefitinib, 21 (15%) achieved a partial
      response. The median age of the responders was 64 years (range, 38-87 years), the
      median Karnofsky performance score was 80 (range, 60-90), and 4 of the patients
      were men. All responders had adenocarcinoma. The central nervous system (CNS) was
      the initial site of disease recurrence in 7 (33%) patients (BM in 5 and LM in 2).
      In 9 (43%) patients, the initial site of disease recurrence was the lung and in 1
      it was the liver and bone. Four (57%) of the patients with disease recurrence in
      the CNS had lung disease under control. BM also developed in 2 patients who had
      initial disease recurrence in the lungs. The actuarial 5-year incidence of CNS
      metastases was 60%. The median overall survival periods were 15 months and 23
      months for patients with and without CNS metastases, respectively (P = 0.24).
      CONCLUSIONS: The CNS was a frequent site of disease recurrence in patients with
      NSCLC after an initial response to gefitinib, regardless of disease control in
      the lungs. Patients should be carefully monitored for neurologic symptoms.
      Intrinsic resistance of metastatic clones, incomplete CNS penetrance of the drug,
      and longer survival are possible explanations for this high incidence.

PMID- 15844175
TI  - Eye and vision in the subterranean rodent cururo (Spalacopus cyanus,
      Octodontidae).
AB  - Subterranean mammals are generally considered to have reduced eyes and apparent
      blindness as a convergent adaptation to their lightless microhabitat. However,
      there are substantial interspecific differences. We have studied the prospect of
      vision in the Chilean subterranean rodent cururo (Spalacopus cyanus,
      Octodontidae) by analyzing the optical properties of the eye, the presence and
      distribution of rod and cone photoreceptors, and their spectral sensitivities.
      Cururo eye size is normal for rodents of similar body size, the cornea and lens
      are transparent from red to near-UV light, and the retina is well-structured.
      Electroretinography reveals three spectral mechanisms: a rod with peak
      sensitivity (lambda(max)) at about 500 nm, a cone with lambda(max) at about 505
      nm (green-sensitive L-cone), and a cone with lambda(max) near 365 nm (UV
      sensitive S-cone). This suggests dichromatic color vision. Immunocytochemistry
      with opsin-specific antibodies confirms the presence of rods, L-cones, and S
      cones. Cururo rod density is much lower than that of nocturnal surface-dwelling
      rodents, and the cones form an unexpectedly high 10% proportion of the
      photoreceptors. Of these, S-cones constitute a regionally varying proportion from
      2% in dorsal to 20% in ventral retina. The high cone proportion suggests
      adaptation to visual demands during the sporadic short phases of diurnal surface
      activity, rather than to the lightless subterranean environment. Our measurements
      on fresh cururo urine reveal a high UV reflectance, suggesting that scent marks
      may be visible to the UV-sensitive cones. The present results challenge the
      general view of convergent adaptive eye reduction and blindness in subterranean
      mammals.

PMID- 15844176
TI  - Hormone receptor status and survival in a population-based cohort of patients
      with breast carcinoma.
AB  - BACKGROUND: The objective of this study was to assess hormone receptor status as
      an independent predictor of survival in a population-based cohort of women with
      breast carcinoma who were followed for up to 11 years. METHODS: Since 1990, the
      National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)
      Program has collected data on hormone receptor status among patients with breast
      carcinoma. In a cohort of 205,736 women with breast carcinoma age > or = 20 years
      at diagnosis who were entered into the SEER data base between 1990 and 2000, the
      authors analyzed the association of hormone receptor status with year of
      diagnosis, patient age, disease stage, tumor histology, tumor grade,
      race/ethnicity, and metropolitan/statewide residence areas. Kaplan-Meier survival
      curves were compared according to hormone receptor status, and Cox proportional
      hazards regression models were used to assess the association of hormone receptor
      status with breast carcinoma-specific and all-cause mortality controlling for
      age, disease stage, tumor grade, tumor histology, race/ethnicity, and SEER
      region. RESULTS: Women who had tumors that were positive for both estrogen and
      progesterone hormone receptors had significantly better survival than other women
      with breast carcinoma in the overall cohort, within each stage, and in the
      younger and older age groups, although the survival advantage was greater among
      women age < or = 50 years than among older women. Hormone receptor status was
      associated with mortality even when patient age, disease stage, tumor grade,
      tumor histology, race/ethnicity, and metropolitan/statewide residence areas were
      taken into account. CONCLUSIONS: Hormone receptor status was identified as an
      independent predictor of outcome in women with breast carcinoma. Data from
      clinical trials with long follow-up may shed light on whether and how the benefit
      of hormonal and other treatment varies with hormone receptor status.

PMID- 15844177
TI  - Expression of xeroderma pigmentosum A protein predicts improved outcome in
      metastatic ovarian carcinoma.
AB  - BACKGROUND: The nucleotide excision repair (NER) proteins repair DNA adducts due
      to xenobiotics and cancer chemotherapy. The authors hypothesized that expression
      of the NER protein xeroderma pigmentosum A (XPA) would be reduced in a clinically
      significant fashion in metastatic ovarian carcinoma. METHODS: Malignant effusion
      specimens were studied so that there was a uniform metastatic ovarian carcinoma
      population for study. XPA protein expression was analyzed by immunocytochemistry
      in 142 effusion specimens (109 peritoneal specimens, 33 pleural specimens) from
      125 patients. Specimens were obtained at diagnosis (n = 76), and at disease
      recurrence (n = 66). Patients in the latter group received platinum-based
      chemotherapy. RESULTS: XPA was expressed in cancer cells in 136 of the 142 (96%)
      effusion specimens. Strongest expression occurred in leukocytes and reactive
      mesothelial cells. XPA expression did not correlate with treatment status,
      effusion site, International Federation of Gynecology and Obstetrics stage,
      histologic grade, or the extent of residual disease. More effusion tumor cells
      from patients with a complete response to chemotherapy expressed XPA compared
      with those with a partial or no response (P = 0.03, chi(2) test). Patients with
      recurrent disease with XPA expressed in > 25% of tumor cells had better
      progression-free survival (PFS) by univariate analysis (median = 0 vs. 11 months,
      P < 0.001; 95% confidence interval [CI], 1-5, 8-14) and overall survival (OS;
      median = 24 vs. 34 months, P = 0.04; 95% CI, 17-31, 24-44). XPA was the only
      predictor of PFS outcome by multivariate analysis (P = 0.03). CONCLUSIONS: The
      results of the current study showed that XPA was widely expressed in metastatic
      ovarian carcinoma effusion specimens and in the cells of the effusion
      microenvironment. Paradoxically, XPA expression was associated with better
      response to chemotherapy and predicted better PFS and OS.

PMID- 15844178
TI  - Contractile activity of skeletal musculature involved in breathing is essential
      for normal lung cell differentiation, as revealed in Myf5-/-:MyoD-/- embryos.
AB  - In the current study, the role of contractile activity of respiratory muscles in
      fetal lung growth and cell differentiation was examined using Myf5-/-:MyoD-/-
      mouse embryos. As previously found, Myf5-/-:MyoD-/- mouse embryos had no
      respiratory musculature. Consequently, they suffered from pulmonary hypoplasia
      and died shortly after birth. The hypoplastic lung had decreased proliferation
      and increased apoptotic index as early as embryonic day 14.5. By contrast, only
      at the last gestational day, the number of lung cells expressing platelet derived
      growth factor B and insulin growth factor I was decreased, while the gradient of
      the thyroid transcription factor 1 was not maintained. Type II pneumocytes had a
      failure in glycogen utilization and surfactant storage and secretion but were
      able to synthesize the surfactant-associated proteins. Type I pneumocytes were
      readily detectable using an early differentiation marker (i.e., Gp38). However,
      the late differentiation of type I pneumocytes never occurred, as revealed by
      transmission electron microscopy. Together, our findings suggest that pulmonary
      distension due to fetal breathing-like movements plays an important role not only
      in lung growth but also in lung cell differentiation.

PMID- 15844179
TI  - Angiosarcoma after breast-conserving therapy: fine-needle aspiration biopsy,
      immunocytochemistry, and clinicopathologic correlates.
AB  - BACKGROUND: Angiosarcoma that arises after breast-conserving therapy can present
      clinically as a cutaneous and/or subcutaneous breast lump, which is
      misinterpreted easily as a recurrence of carcinoma. To the authors' knowledge,
      the role of fine-needle aspiration (FNA) cytology in the early diagnosis of this
      life-threatening complication of breast carcinoma therapy has not been
      established fully. METHODS: The authors studied three new patients with this type
      of secondary angiosarcoma diagnosed by FNA biopsy and immunocytochemistry,
      reviewed the literature on the topic, and examined relevant differential
      diagnostic issues. RESULTS: Patients presented with a discrete skin lump that had
      arisen several years after breast-conservative therapy for early-stage breast
      carcinoma near the scar from the previous surgery. The lesions were interpreted
      clinically as recurrent carcinoma. FNA yielded moderately cellular to highly
      cellular samples with variable patterns of cellular aggregation. Cells were
      epithelioid and spindle-shaped. Angioformative changes were subtle, and the
      overall picture suggested an epithelial malignancy, possibly a metaplastic
      carcinoma. Immunostaining of smears, however, provided conclusive evidence of the
      endothelial differentiation of tumor cells, and an FNA diagnosis of angiosarcoma
      was rendered in all patients. The histopathology of all surgically excised tumors
      confirmed the diagnosis of high-grade angiosarcoma. CONCLUSIONS: Based on the
      authors' experience, the FNA cytologic appearance of angiosarcoma that presented
      as a breast skin nodule in a breast carcinoma survivor easily could have been
      misinterpreted as carcinoma. A correct diagnosis of this tumor relies on the
      proper evaluation of clinical findings and, as also shown by a review of the
      literature, requires immunocytochemical evidence of endothelial differentiation.

PMID- 15844181
TI  - Extended survival in a patient with recurrent and metastatic adrenal cortical
      carcinoma by aggressive transarterial embolization--a case report.
AB  - The prognosis of inoperable recurrent or metastatic adrenal cortical carcinoma is
      poor due to lack of effective treatment modalities. We report a case of recurrent
      and metastatic adrenal cortical carcinoma in which prolonged survival of 58
      months was achieved with aggressive three sequential transarterial embolization.
      It is probably the first reported case with the longest survival by transarterial
      embolization in the literature to date. A 60-year-old man received operation for
      left adrenal cortical carcinoma. Liver metastases, tumor bed recurrence, and
      spleen metastasis were noted during follow-up. Three sequential transarterial
      embolization for metastatic liver tumors, tumor bed recurrence, and metastatic
      spleen tumor were performed and resulted in relief of symptoms and prolonged
      survival of 58 months after recurrence verified. Aggressive transarterial
      embolization seems to be a safe and effective procedure for symptoms relief, and
      may prolong survival in the management of inoperable adrenal cortical carcinoma.
      It can be considered in any patient with inoperable adrenal cortical carcinoma if
      not contraindicated.

PMID- 15844180
TI  - Expression of RCAS1 in esophageal squamous cell carcinoma is associated with a
      poor prognosis.
AB  - BACKGROUND: Receptor-binding cancer antigen expressed on SiSO cells (RCAS1) has
      been reported to act as a ligand for a receptor present on normal peripheral
      lymphocytes and to induce apoptotic cell death. We aimed to elucidate the
      significance of RCAS1 expression in human esophageal squamous cell carcinomas
      (ESCC). METHODS: RCAS1 expression was examined immunohistochemically in
      surgically resected esophageal carcinoma tissues from 114 patients. We also
      examined the relationships between RCAS1 expressions, the tumor Ki-67 indices (a
      marker of proliferation), and the number of CD8+ tumor-infiltrating lymphocytes
      (TILs). RESULTS: RCAS1 immunoreactivity was detected in the membranes and
      cytoplasm of the tumor cells. Of the 114 esophageal carcinomas, 39 (34.2%) were
      strongly positive for RCAS1 immunostaining on the membranes of the cancer cells,
      41 (36.0%) were weakly positive, and 34 (29.8%) were negative. A comparison of
      RCAS1 expression and clinicopathological characteristics in all 114 patients
      revealed significant associations between RCAS1 expression and lymph node status
      (P < 0.05), and pathologic stage (P < 0.05). The survival rates of patients with
      RCAS1-negative tumors were significantly higher than those of patients with both
      RCAS1-weak positive tumors and RCAS1-strong positive ones (log-rank P < 0.05).
      Multivariate analysis revealed that RCAS1 positivity was an independent
      prognostic factor (P < 0.05). The relationship between RCAS1 expression and the
      numbers of CD8+ T-cells in the primary tumors revealed that RCAS1-negative tumors
      tended to contain more of these cells than both RCAS1-weak positive tumors and
      RCAS1-strong positive ones (P = 0.2495). CONCLUSIONS: RCAS1 may play a
      significant role in tumor progression via an immune escape mechanism; thus, RCAS1
      expression could be used as a predictor of poor prognosis in patients with ESCC.

PMID- 15844182
TI  - Significance of serum S-100B in melanoma patients before and after sentinel node
      biopsy.
AB  - BACKGROUND AND OBJECTIVES: The clinical utility of the tumor marker serum S-100B
      has been described in determining prognosis, for early diagnosis of recurrence
      and for disease monitoring in melanoma patients. Sentinel node biopsy is
      increasingly used as staging procedure for patients with clinically localized
      melanoma. The aim of this study was to determine the value of serum S-100B in
      melanoma patients before and after sentinel lymph node biopsy. METHODS: S-100B
      values were measured prior to sentinel node biopsy in 89 patients and during
      follow-up (median 41 months; range 7-73 months) in 88 patients. The detection
      limit is < or =0.08 microg/L. In our laboratory levels of 0.16 microg/L and above
      are classified as increased. RESULTS: Twenty-four patients had tumor-positive
      sentinel nodes, 65 had tumor-free sentinel nodes. The median S-100B value prior
      to the operation was < or =0.08 microg/L for all patients. Sensitivity and
      specificity of S-100B to predict the tumor-status of the sentinel node were 13%
      and 98%, respectively. Eighteen patients developed a melanoma-related recurrence.
      Sensitivity for early diagnosis of recurrence was 55% and 33%, respectively for
      patients with a positive versus a negative sentinel node. Specificity was 100% in
      both patient groups. CONCLUSIONS: S-100B is not useful in predicting the tumor
      status of the sentinel node, and questionable for early diagnosis of recurrence
      afterwards. Elevation of serum S-100B is highly specific for melanoma recurrence.

PMID- 15844185
TI  - Detection of peritoneal micrometastasis by reverse transcriptase-polymerase chain
      reaction for heparanase mRNA and cytology in peritoneal wash samples.
AB  - BACKGROUND: Peritoneal dissemination is the most common pattern of metastasis in
      advanced gastric carcinoma with serosal invasion. In the present study, we have
      reported the clinical relevance of a new diagnostic method with reverse
      transcriptase-polymerase chain reaction (RT-PCR) assay using heparanase as a
      target gene for detection of free cancer cells in peritoneal washes. METHODS:
      Intraoperative peritoneal washes were obtained from 48 patients who underwent
      surgery for gastric cancer. RT-PCR analysis with primers specific for heparanase
      and conventional cytological examination were performed subsequently. RESULTS:
      Heparanase RT-PCR was capable of detecting at least 10 tumor cells in 10 ml
      peritoneal wash fluid. There was no detectable heparanase expression in normal
      gastric epithelial cells and peritoneal wash samples from patients with benign
      disease. Twenty-five (52%) patients with gastric cancer had a detectable
      heparanase expression. Its positive rate was 100% and 59% for the cases with
      clinically evident peritoneal metastasis and serosal invasion, respectively, both
      of which are higher than that of cytology. CONCLUSIONS: Heparanase mRNA detected
      in peritoneal lavaged fluid might indicate the presence of free cancer cells in
      peritoneal cavity. The high sensitivity of RT-PCR based heparanase assay made it
      a candidate molecular marker for detecting peritoneal micrometastasis.

PMID- 15844186
TI  - Commentary on Wang et al., "Pre-operative chemotherapy with oral tegafur-uracil
      and leucovorin for rectal cancer" (J Surg Oncol 89: 256-263).

PMID- 15844187
TI  - Cytoreductive surgery and intraoperative hyperthermic chemoperfusion for advanced
      ovarian carcinoma.
AB  - BACKGROUND: Optimal cytoreductive surgery combined with intraoperative
      hyperthermic chemoperfusion (IHCP) is a therapy that potentially could improve
      survival in a select group of patients with advanced ovarian cancer. The purpose
      of this study was to review the results of cytoreductive surgery and IHCP for
      advanced ovarian cancer and to identify factors that may predict which patients
      maximally benefit from this aggressive treatment. METHODS: Patients treated with
      cytoreduction followed by IHCP for ovarian cancer were identified from an IHCP
      database from 1/2001 through 3/2004. Several factors including resection status,
      peritoneal cancer index (PCI), and prior surgery were evaluated for their ability
      to predict survival in our cohort of patients. RESULTS: Thirteen patients with
      ovarian cancer treated with cytoreductive surgery followed by IHCP were
      identified. The 3-year overall survival rate for all thirteen patients was 55%.
      The median disease-free survival was 15.4 months (3-year disease-free survival,
      11%). Several factors including PCI score (<6), ability to resect all gross
      disease, and previous surgical exploration appeared to impart an overall survival
      advantage. CONCLUSIONS: The use of IHCP coupled with optimal cytoreduction is a
      safe and effective treatment for advanced ovarian carcinoma. However, the proper
      selection of patients who will benefit most from the therapy is essential for the
      success of the treatment.

PMID- 15844188
TI  - Activation of MMP-2 and MMP-9 in patients with oral squamous cell carcinoma.
AB  - BACKGROUND AND OBJECTIVES: Oral cancer accounts for one third of all malignancies
      in India where habit of tobacco consumption is the major etiologic factor, which
      causes field cancerization in oral mucosa. Multiple molecular events in oral
      mucosa due to field cancerization may be the cause of local and regional lymph
      node involvement in oral cancer resulting into low overall survival, high
      recurrence rate, and poor prognosis. Several matrix metalloproteinases (MMPs)
      have been shown to play an important role in the invasion and metastasis of oral
      squamous cell carcinoma (SCC). MMP-2 and MMP-9 are capable of degrading type-IV
      collagen, which is a major component of basement membrane. Therefore, we studied
      MMP-2 and MMP-9 activation by gelatin zymography, which is cost effective
      alternate to ELISA method, in patients with oral SCCs to predict their role in
      metastatic potentials. MATERIALS AND METHODS: Thirty-nine patients of oral SCCs
      were classified as non-metastatic (n = 28), and metastatic (n = 11) according to
      regional lymph node involvement. Malignant and adjacent normal tissues of the
      patients were collected at the time of surgery. Gelatin zymography was carried
      out using 7.5% polyacrylamide gel under non-denaturing and non-reducing
      conditions. Zymograms were analyzed densitometrically. Latent and active forms of
      MMP-2 and MMP-9 were expressed as ng/50 microg of protein. RESULTS: Latent and
      active forms of MMP-2 and MMP-9 were significantly elevated in malignant tissues
      as compared to their adjacent normal tissues (P < 0.05). Total MMP-2 and MMP-9
      activities were also significantly elevated in malignant tissues as compared to
      adjacent normal tissues (P = 0.005 and P = 0.028, respectively). Activation ratio
      of MMP-2 and MMP-9 were significantly elevated in malignant tissues as compared
      to adjacent normal tissues. Activation of MMP-2 was prominent (11%) than MMP-9
      (5%) in malignant tissues. Activation ratio of MMP-2 was significantly elevated
      in patients with lymph node metastasis than patients without lymph node
      metastasis (P = 0.005). Receiver's operating characteristic (ROC) curve analysis
      revealed that activation ratio of MMP-2 discriminate better than and activation
      ratio of MMP-9 between patients with and without lymph node metastasis.
      Activation ratio of MMP-2 could predict risk of lymph node metastasis development
      in patients without lymph node involvement. CONCLUSION: The study concluded that
      activation of MMP-2 and MMP-9 was significantly higher in malignant tissues as
      compared to adjacent normal tissues. Further, activation ratio of MMP-2 was
      significantly elevated in patients with lymph node metastasis as compared to
      patients without lymph node metastasis, which could predict risk of lymph node
      metastasis development in node negative patients.

PMID- 15844189
TI  - Extended multiorgan resection for T4 gastric carcinoma: 25-year experience.
AB  - BACKGROUND AND OBJECTIVES: In locally advanced gastric carcinoma infiltrating
      adjacent organs, an extended resection including invaded organs is required to
      improve the prognosis. We retrospectively analyzed our experience with extended
      multiorgan resection (EMR) in patients with advanced gastric cancer. METHODS:
      Between December 1979 and April 2004, 65 patients were resected for extended
      gastric carcinoma macroscopically invading other organs. Various
      clinicopathologic factors influencing early and late results were evaluated.
      Survival rates were calculated according to the Kaplan-Meier method. Prognostic
      factors were evaluated by univariate and multivariate analysis. RESULTS: The
      majority of patients (61.5%) did receive a R0 curative resection. In 52 (80%) of
      the 65 presumed T4 cancers, histologic final analysis confirmed invasion.
      Postoperative morbidity and mortality was 27.7% and 12.3%, respectively.
      Actuarial 5-year overall survival (OS) rate was 21.8%. It was significantly
      better in R0 versus R+ (30.6% vs. 0%, P = 0.001). Multivariate analysis
      identified curative resection as the strongest predictor of survival (P = 0.002).
      CONCLUSIONS: Patients with locally advanced gastric carcinoma invading adjacent
      organs can benefit from aggressive surgical treatment with acceptable morbidity
      and mortality. However, curative resection is mandatory to improve prognosis.

PMID- 15844190
TI  - Ductal carcinoma in situ in core biopsies containing invasive breast cancer:
      correlation with extensive intraductal component and lumpectomy margins.
AB  - BACKGROUND AND OBJECTIVES: The diagnosis of invasive breast cancer is most
      commonly made on image-guided core biopsy (CB). The presence of extensive
      intraductal component (EIC), as identified on subsequent lumpectomy, is
      associated with an increased risk of positive margins and need for further
      surgery. CBs demonstrating invasive breast cancer may also contain ductal
      carcinoma in situ (DCIS), although the significance of this finding is unclear.
      The objective of this study was to examine the implications of DCIS found in the
      original CB, specifically related to the risk of EIC and/or positive lumpectomy
      margins. METHODS: All patients at a single academic institution who underwent
      initial breast conserving surgery for invasive breast cancer diagnosed on image
      guided CB between 05/00 and 04/02 were included in the study. A systematic,
      blinded review of all CB and lumpectomy specimens was performed using
      standardized criteria for DCIS, EIC, and margins. RESULTS: A total of 95 patients
      were included in the study, with a mean of 5 (median 5) CB/patient. Of these, 43
      (45%) patients had DCIS identified in their CB; in 34 (79%) of these patients,
      the DCIS was mixed with the invasive cancer. No differences in tumor size or
      lumpectomy volume were identified between patients with or without DCIS on CB.
      However, patients with DCIS were noted to be significantly younger. Overall, EIC
      was identified in 13 (14%) patients; the risk of EIC was significantly higher in
      patients with DCIS identified in CB than in those with invasive carcinoma alone
      (30% vs. 0%, respectively; P < 0.0001). Expectedly, the incidence of positive
      margins on lumpectomy was higher in patients with EIC (38% vs. 16%; P = 0.05). A
      trend, although not statistically significant, towards positive margins was also
      noted in patients with DCIS on CB compared to those with invasive carcinoma alone
      (24% vs. 15%, P = 0.3). CONCLUSIONS: The identification of DCIS in conjunction
      with invasive cancer on CB appears important; the absence of DCIS in a CB sample
      excludes the possibility of eventually identifying EIC. Knowledge of DCIS in CBs
      with invasive carcinoma may be helpful for surgeons in planning gross resection
      margins at lumpectomy.

PMID- 15844191
TI  - Quantification of angiogenesis induced in rabbit cornea by breast carcinoma of
      women treated with tamoxifen.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of tamoxifen on
      angiogenesis induced in rabbit cornea by breast carcinoma from post-menopausal
      women. METHODS: Thirteen post-menopausal women with operable, estrogen receptor
      positive breast carcinomas, treated with 20 mg of tamoxifen daily for 30 days
      prior to undergoing definitive surgery, participated in this study. Twenty-six
      virgin female New Zealand white rabbits, 3-4 months old, weighing approximately
      2.5 kg each, were divided into two groups of 13 animals and received corneal
      implants of tumor either pre- or post-tamoxifen treatment. After 10 days, the
      animals were sacrificed, the region of the cornea between the tumor implant and
      the limbus was removed and quantification of angiogenesis was carried out by
      evaluating the entire hematoxylin-eosin stained slide, using a 10x objective lens
      (100x magnification). Student t-test was used in the statistical analysis of the
      data and statistical significance was established at P < 0.05. RESULTS: Mean
      microvessel count was 106.8 +/- 5.9 pre-tamoxifen treatment and 54 +/- 5.6 post
      treatment. According to Student t-test, there was a significant reduction in mean
      microvessel density following treatment with tamoxifen (P < 0.001). CONCLUSIONS:
      Rabbit cornea proved to be an interesting experimental model for the
      quantification of angiogenesis. Tamoxifen, when administered for 30 days to post
      menopausal women with breast cancer, significantly inhibited angiogenesis induced
      by tumor fragments in rabbit cornea.

PMID- 15844192
TI  - Regionalization of the anterior hypothalamus in the chick embryo.
AB  - Loss-of-function experiments in mice have shown that the transcription factors
      Sim1, Otp, Sim2, and Brn2 form a cascade essential for the differentiation of
      neuroendocrine cells of the anterior hypothalamus that produce vasopressin,
      oxytocin, somatostatin (SS), thyrotropin-releasing hormone (TRH), and
      corticotropin-releasing hormone (CRH). Very little is known about how the
      differentiation of these cell types is regulated in chick. Here, we report the
      cloning of the chick homolog of Otp. Moreover, we have systematically compared
      the expression of Sim1, Sim2, Brn2, and Otp with that of the markers of terminal
      differentiation TRH, SS, CRH, vasotocin, and mesotocin during development of
      chick embryos. We have found that the cell types studied generally develop in
      domains expressing these transcriptional regulators but that the pattern of
      neuronal differentiation and the spatial distribution of some regulators were not
      the same as in mice. Our results provide a framework useful for the functional
      analysis of hypothalamus development in chick.

PMID- 15844193
TI  - Distinctive biology of pleomorphic lobular carcinoma of the breast.

PMID- 15844194
TI  - Genetic analysis of metamorphic and premetamorphic Xenopus ciliary marginal zone.
AB  - A major event affecting the eye during amphibian metamorphosis is an asymmetrical
      growth of the ventrotemporal portion of the retina compared with its dorsonasal
      counterpart. This event is due to an increased proliferation of the precursors of
      the ventral ciliary marginal zone (CMZ). Here, we analyze the expression patterns
      of several key homeobox genes implicated in eye development (Xrx1, Xvax2, Xsix3,
      Xpax6, Xchx10, Xotx2) to understand whether they are active at the time in which
      the metamorphic changes of the retina occur. We also analyze their expression
      patterns in the ventral and dorsal CMZ and compare them with bromodeoxyuridine
      incorporation in the CMZ. Our results suggest that the metamorphic CMZ maintains
      the functional subdivisions described during embryonic development. Moreover, we
      find that genes involved in proliferation and cell type determination of the
      embryonic retina are actively transcribed in the proliferating CMZ, thus
      indicating a potential regulatory role for these genes in the metamorphic retina.

PMID- 15844195
TI  - Proprotein convertase genes in Xenopus development.
AB  - Proprotein convertases (PCs) are a family of serine endoproteases that
      proteolytically activate many precursor proteins within various secretory pathway
      compartments. Loss-of-function studies have demonstrated a critical role for
      these proteases in embryonic patterning and adult homeostasis, yet little is
      known about how substrate selectivity is achieved. We have identified Xenopus
      orthologs of three PCs: furin, PC6, and PC4. In addition to previously described
      isoforms of PC6 and furin, four novel splice isoforms of PC6, which are predicted
      to encode constitutively secreted proteases, and a putative transmembrane isoform
      of PC4 were identified. Furin and PC6 are expressed in dynamic, tissue-specific
      patterns throughout embryogenesis, whereas PC4 transcripts are restricted
      primarily to germ cells and brain in adult frogs.

PMID- 15844196
TI  - dazed gene is necessary for late cell type development and retinal cell
      maintenance in the zebrafish retina.
AB  - Several molecules, such as growth factors and neurotrophic factors, are required
      both for the differentiation of specific retinal cell types and the long-term
      cell survival of all retinal neurons. As diffusible factors, these molecules act
      non-cell-autonomously. Here, we describe the loss of function phenotype for dazed
      (dzd), a gene that acts cell-autonomously for retinal cell survival and affects
      the differentiation of rod photoreceptors and the Muller glia. By 3 days after
      fertilization, dazed mutant embryos have small eyes and slight heart edema.
      Acridine orange staining indicated a significant degree of retinal cell death
      occurring by 48 hr after fertilization, and histological analysis revealed that
      dying cells were found in the inner and outer nuclear layers and near the
      marginal zones. Although molecular and morphological differentiation of the inner
      retina and cone photoreceptors occurred, rod photoreceptors failed to
      differentiate beyond a small patch in the ventral retina and rod precursors
      failed to respond to exogenously added retinoic acid, which normally potentiated
      rod differentiation. Mosaic analysis indicated that the dazed gene acts cell
      autonomously for rod production and cell survival, as dazed clones failed to
      produce rods outside the ventral patch and dazed cells were not maintained in
      wild-type hosts. Raising mutants under constant light resulted in severe retinal
      degeneration, whereas raising embryos under constant darkness did not provide any
      additional protection from cell death. Behavioral analysis showed that a
      subpopulation of adult fish that were heterozygous for the dazed mutation had
      elevated visual thresholds and were night blind, suggesting that dazed may also
      be required for long-term dim-light vision. Taken together, our studies suggest a
      role for the dazed gene in rod and Muller cell development and overall retinal
      cell survival and maintenance.

PMID- 15844197
TI  - Cardiac morphogenesis: matrix metalloproteinase coordination of cellular
      mechanisms underlying heart tube formation and directionality of looping.
AB  - During heart organogenesis, the spatiotemporal organization of the extracellular
      matrix (ECM) undergoes significant remodeling. Because matrix metalloproteinases
      (MMPs) are known to be key regulators of cell-matrix interactions, we analyzed
      the role(s) of MMPs, and specifically MMP-2, in early heart development. Both MMP
      2 neutralizing antibody and the broad-spectrum MMP inhibitor Ilomastat in a
      temporal manner, when applied between chick embryonic stages 5 (primitive streak
      stage) to stage 12 ( approximately 16-somites), produced severe heart tube
      defects. Exposure to the MMP inhibitor at stage 5 produced various degrees of
      cardia bifida. At the seven-somite stage, MMP-2/Ilomastat inhibition caused a
      shift in normal left-right patterning of cell proliferation within the dorsal
      mesocardium and mesoderm of the anterior heart field that correlated with a
      change in looping direction. MMP inhibition at the 10- to 12-somite stage
      resulted in an arrest of heart tube bending by inhibiting the breakdown of the
      dorsal mesocardial ECM. The experimental observations suggest that MMP activity
      regulates the coordination of early heart organogenesis by affecting ventral
      closure of the heart and gut tubes, asymmetric cell proliferation in the dorsal
      mesocardium to drive looping direction, and ECM degradation within the dorsal
      mesocardium allowing looping to proceed toward completion.

PMID- 15844199
TI  - Muscle fiber differentiation in fish embryos as shown by in situ hybridization of
      a large repertoire of muscle-specific transcripts.
AB  - Skeletal muscles are composed of different fiber types, largely defined by
      differential expression of protein isoforms involved in myofibrillogenesis or
      metabolism. To learn more about the gene activations that underlie the
      differentiation and the diversification of embryonic fish myotomal fibers, we
      investigated the developmental expression of 25 muscle genes in trout embryos by
      in situ hybridization of muscle-specific transcripts. The earliest event of
      muscle differentiation, at approximately the 25-somite stage, was the expression
      of a variety of muscle-specific genes, including slow-twitch and fast-twitch
      muscle isoforms. The activation of these muscle genes started in the deep somitic
      domain, where the slow muscle precursors (the adaxial cells) were initially
      located, and progressively spread laterally throughout the width of the myotome.
      This mediolateral progression of gene expression was coordinated with the lateral
      migration of slow adaxial cells, which specifically expressed the slow myosin
      light chain 1 and the SLIM1/FHL1 genes. Subsequently, the fast and slow skeletal
      muscle isoforms precociously expressed in the course of the mediolateral wave of
      muscle gene activation became down-regulated in the superficial slow fibers and
      the deep fast fibers, respectively. Finally, several muscle-specific genes,
      including troponins, a slow myosin-binding protein C, tropomodulins, and
      parvalbumin started their transcription only in late embryos. Taken together,
      these findings show in fish embryos that a common myogenic program is triggered
      in a mediolateral progression in all muscle cells. The acquisition of the slow
      phenotype involves the additional activation of several slow-specific genes in
      migrating adaxial muscle cells. These events are followed by sequential gene
      activations and repressions in fast and slow muscle cells.

PMID- 15844198
TI  - Atoh1 null mice show directed afferent fiber growth to undifferentiated ear
      sensory epithelia followed by incomplete fiber retention.
AB  - Inner ear hair cells have been suggested as attractors for growing afferent
      fibers, possibly through the release of the neurotrophin brain-derived
      neurotrophic factor (BDNF). Atoh1 null mice never fully differentiate hair cells
      and supporting cells and, therefore, may show aberrations in the growth and/or
      retention of their innervation. We investigated the distribution of cells
      positive for Atoh1- or Bdnf-mediated beta-galactosidase expression in Atoh1 null
      and Atoh1 heterozygotic mice and correlated the distribution of these cells with
      their innervation. Embryonic day (E) 18.5 Atoh1 null and heterozygotic
      littermates show Atoh1- and BDNF-beta-galactosidase-positive cells in comparable
      distributions in the canal cristae and the cochlea apex. Atoh1-beta-galactosidase
      positive but only occasional Bdnf-beta-galactosidase-positive cells are found in
      the utricle, saccule, and cochlea base of Atoh1 null mutant mice. Absence of Bdnf
      beta-galactosidase expression in the utricle and saccule of Atoh1 null mice is
      first noted at E12.5, a time when Atoh1-beta-galactosidase expression is also
      first detected in these epithelia. These data suggest that expression of Bdnf is
      dependent on ATOH1 protein in some but does not require ATOH1 protein in other
      inner ear cells. Overall, the undifferentiated Atoh1- and Bdnf-beta-galactosidase
      positive cells show a distribution reminiscent of that in the six sensory
      epithelia in control mice, suggesting that ear patterning processes can form
      discrete patches of Atoh1 and Bdnf expression in the absence of ATOH1 protein.
      The almost normal growth of afferent and efferent fibers in younger embryos
      suggests that neither fully differentiated hair cells nor BDNF are necessary for
      the initial targeted growth of fibers. E18.5 Atoh1 null mice have many afferent
      fibers to the apex of the cochlea, the anterior and the posterior crista, all
      areas with numerous Bdnf-beta-galactosidase-positive cells. Few fibers remain to
      the saccule, utricle, and the base of the cochlea, all areas with few or no Bdnf
      beta-galactosidase-positive cells. Thus, retention of fibers is possible with
      BDNF, even in the absence of differentiated hair cells.

PMID- 15844200
TI  - Beta-catenin-mediated cell-adhesion is vital for embryonic forebrain development.
AB  - Forming a complex structure such as the mammalian brain requires a complex
      interplay between cells and different signalling cascades during embryonic
      development. beta-catenin plays pivotal roles in these processes by mediating
      cadherin-based cell adhesion and Wnt signalling. We show for the first time that
      beta-catenin functions predominantly as a mediator of cell adhesion during early
      development of the mammalian telencephalon. Immunohistochemical analysis
      demonstrates that beta-catenin is localized, together with N-cadherin, to
      adhesion junctions at the apical lining of the neuroepithelium. The ablation of
      beta-catenin specifically from the forebrain leads to a disruption of apical
      adherens junctions and a breakdown of neuroepithelial structures. We show that
      beta-catenin-deficient neuroepithelial cells delaminate and undergo apoptosis.
      Newborn beta-catenin mutants lack the entire forebrain and anterior facial
      structures. Our data also indicate a lack of TCF/LEF-beta-catenin-dependent
      transcriptional activity in the telencephalon of Wnt reporter embryos. Together
      with the absence of nuclear beta-catenin, this finding suggests that canonical
      Wnt signalling is not active during early telencephalic development. In summary,
      we demonstrate that beta-catenin mediates cell-cell adhesion in the early
      telencephalon and is vital for maintaining the structural integrity of the
      neuroepithelium.

PMID- 15844201
TI  - Organization of Hox genes in ascidians: present, past, and future.
AB  - Hox genes have been regarded to play a central role in anterior-posterior
      patterning of the animal body. Variations of Hox genes among animal species in
      the number, order on a chromosome, and the developmental expression pattern may
      reflect an evolutionary history. Therefore, it is definitely necessary to
      characterize Hox genes of wide variety of animal species, especially the species
      occupying key positions in the animal phylogeny. Ascidians, belonging to the
      subphylum Urochordata, are one of the sister groups of vertebrates in the phylum
      Chordata. Recent studies have shown that nine Hox genes of Ciona intestinalis, an
      ascidian species, are present on two chromosomes in the genome. In this review,
      we discuss the present state of Hox genes in ascidians, focusing on their novel
      chromosomal organization and expression pattern with unique features and how the
      novel organization has evolved in relation to the unique body plan of ascidians.

PMID- 15844202
TI  - Prognostic model of event-free survival for patients with androgen-independent
      prostate carcinoma.
AB  - BACKGROUND: The current study was conducted to develop a prognostic model of
      event-free survival (EFS) in men with androgen-independent prostate carcinoma
      (AIPC). METHODS: Data from 160 patients diagnosed with AIPC between 1989-2002
      were reviewed. No patient had received cytotoxic chemotherapy. A univariate Cox
      proportional hazards model identified significant predictors of EFS. Recursive
      partitioning analysis divided these significant variables into prognostic risk
      groups. The final prognostic model was tested with a Cox proportional hazards
      model. RESULTS: The final prognostic risk model included the presence of
      metastatic disease at the time of androgen-independent disease progression (P =
      0.040), time to prostate-specific antigen (PSA) recurrence (P = 0.043), and PSA
      doubling time (P < 0.01). Three highly independent risk groups were identified.
      The observed median EFSs were 6.1 months (95% confidence interval [95= CI], 3.4
      8.8 months), 33.6 months (95= CI, 25.3-41.9 months), and 96.1 months (95= CI,
      57.9-134.3 months) for the low-risk, intermediate-risk, and high-risk groups,
      respectively. Each risk group was found to be independently predictive of EFS (P
      < 0.01). Patients who died of prostate carcinoma experienced significantly more
      clinical events than those who died of other causes (P < 0.01). CONCLUSIONS: The
      prognostic model in the current study stratified patients into three highly
      significant and independent risk groups for EFS. A detailed PSA history and
      knowledge of metastatic disease are sufficient to risk-stratify patients with
      AIPC. One very unique aspect of this model was that it was developed from a
      patient cohort that never received chemotherapy.

PMID- 15844203
TI  - MTHFR 677C-T polymorphism is not excluded as maternal risk for Down syndrome
      among Turkish women.

PMID- 15844204
TI  - Enantioselective semipreparative HPLC separation of PCB metabolites and their
      absolute structure elucidation using electronic and vibrational circular
      dichroism.
AB  - Polychlorinated biphenyls (PCBs) remain one of the most important groups of
      environmental contaminants. The fate (transformation) as well as the
      toxicological implications of the different metabolism steps are subject to
      considerable debate. The aim of this study is to start a comprehensive
      investigation of atropisomeric PCB metabolites, i.e., hydroxy, methoxy,
      methylthionyl, and methylsulfonyl PCBs in different biota. For this purpose,
      enantioselective semipreparative liquid chromatography is used to obtain pure
      enantiomers of PCB metabolites. Electronic circular dichroism (UV-CD) and
      vibrational circular dichroism (VCD) in combination with computational techniques
      were applied to determine their absolute structures. Approximately 18-25 mg of
      each enantiomer of the following metabolites were obtained using semipreparative
      HPLC on beta-cyclodextrin-based columns: 4-MeO-CB149, 4-MeS-CB149, 4-MeSO2-CB149,
      3-MeS-CB149, and 3-MeSO2-CB149. The enantiomeric purity of the separated
      enantiomers was in the range of 95.0-99.9%. Rotational angles and absolute
      configurations were also determined. This study establishes a sound method for
      future preparation and absolute structure determination of compounds belonging to
      the same class.

PMID- 15844205
TI  - Chiral ionic liquids: synthesis and applications.
AB  - Over the last ten years, interest and publications involving ionic liquids have
      expanded exponentially. Thus far, they have predominantly been used in organic
      synthesis and separations. However, their use is rapidly expanding into other
      areas of science and technology. Research involving chiral ionic liquids has been
      much more limited and only recently has come to the forefront. In this work, we
      review the synthesis of chiral ionic liquids and their use. Today, this is an
      area of research that is poised for rapid development and expansion.

PMID- 15844206
TI  - Reversal of elution order for profen acid enantiomers in packed-column SFC on
      Chiralpak AD.
AB  - Enantiomeric separations of four 2-substituted propionic acid drugs have been
      studied using packed-column supercritical fluid chromatography (SFC) with amylose
      tris(3,5-dimethylphenylcarbamate) coated on silica as support (Chiralpak AD).
      Under standard conditions (i.e., flow rate, 1.5 ml/min; column temperature, 30
      degrees C; back-pressure, 150 bar), the order of elution could be reversed when
      the polar alcohol modifier methanol in carbon dioxide was replaced by 2-propanol
      for ibuprofen, ketoprofen, and naproxen. For flurbiprofen, with the highest
      selectivity factor, no reversal was observed, although selectivity was reduced
      significantly with higher alcohols. Naproxen and flurbiprofen were also
      investigated with 2-butanol and 2-pentanol. The former showed reversal of elution
      order but not the latter. For higher alcohol modifiers, including 2-propanol, the
      peak symmetry was poor but could be improved by addition of citric acid in the
      alcohol modifier. These results stress the importance to investigate enantiomer
      elution order during the development of enantioselective methods and when
      chromatographic conditions are optimized. Preliminary experiments with column
      temperatures over the range of -15 to 45 degrees C revealed that, in a few cases,
      reversal took place with a change in temperature only.

PMID- 15844207
TI  - Chronic depolarization enhances the trophic effects of brain-derived neurotrophic
      factor in rescuing auditory neurons following a sensorineural hearing loss.
AB  - The development and maintenance of spiral ganglion neurons (SGNs) appears to be
      supported by both neural activity and neurotrophins. Removal of this support
      leads to their gradual degeneration. Here, we examined whether the exogenous
      delivery of the neurotrophin brain-derived neurotrophic factor (BDNF) in concert
      with electrical stimulation (ES) provides a greater protective effect than
      delivery of BDNF alone in vivo. The left cochlea of profoundly deafened guinea
      pigs was implanted with an electrode array and drug-delivery system. BDNF or
      artificial perilymph (AP) was delivered continuously for 28 days. ES induced
      neural activity in two cohorts (BDNF/ES and AP/ES), and control animals received
      BDNF or AP without ES (BDNF/- and AP/-). The right cochleae of the animals served
      as deafened untreated controls. Electrically evoked auditory brainstem responses
      (EABRs) were recorded immediately following surgery and at completion of the drug
      delivery period. AP/ES and AP/- cohorts showed an increase in EABR threshold over
      the implantation period, whereas both BDNF cohorts exhibited a reduction in
      threshold (P < 0.001, t-test). Changes in neural sensitivity were complemented by
      significant differences in both SGN survival and soma area. BDNF cohorts
      demonstrated a significant trophic or survival advantage and larger soma area
      compared with AP-treated and deafened control cochleae; this advantage was
      greatest in the base of the cochlea. ES significantly enhanced the survival
      effects of BDNF throughout the majority of the cochlea (P < 0.05, Bonferroni's t
      test), although there was no evidence of trophic support provided by ES alone.
      Cotreatment of SGNs with BDNF and ES provides a substantial functional and
      trophic advantage; this treatment may have important implications for neural
      prostheses.

PMID- 15844208
TI  - Postnatal development of alkaline phosphatase activity correlates with the
      maturation of neurotransmission in the cerebral cortex.
AB  - We have shown previously that the tissue nonspecific alkaline phosphatase (TNAP)
      is selectively expressed in the synaptic cleft of sensory cortical areas in adult
      mammals and, by using sensory deprivation, that TNAP activity depends on
      thalamocortical activity. We further analyzed this structural functional
      relationship by comparing the developmental pattern of TNAP activity to the
      maturation of the thalamocortical afferents in the primate brain (Callithrix
      jacchus). Cortical expression of alkaline phosphatase (AP) activity reflects the
      sequential maturation of the modality-specific sensory areas. Within the visual
      cortex, the regional and laminar distribution of AP correlates with the
      differential maturation of the magno- and parvocellular streams. AP activity,
      which is transiently expressed in the white matter, exhibits a complementary
      distributional pattern with myelin staining. Ultrastructural analysis revealed
      that AP activity is localized exclusively to the myelin-free axonal segments,
      including the node of Ranvier. It was also found that AP activity is gradually
      expressed in parallel with the maturation of synaptic contacts in the neuropile.
      These data suggest the involvement of AP, in addition to neurotransmitter
      synthesis previously suggested in the adult, in synaptic stabilization and in
      myelin pattern formation and put forward a role of AP in cortical plasticity and
      brain disorders.

PMID- 15844209
TI  - Ionotropic glutamate receptors are expressed in GABAergic terminals in the rat
      superficial dorsal horn.
AB  - Ionotropic glutamate receptors (IGR), including NMDA, AMPA, and kainate
      receptors, are expressed in terminals with varied morphology in the superficial
      laminae (I-III) of the dorsal horn of the spinal cord. Some of these terminals
      can be identified as endings of primary afferents, whereas others establish
      symmetric synapses, suggesting that they may be gamma-aminobutyric acid (GABA)
      ergic. In the present study, we used confocal and electron microscopy of double
      immunostaining for GAD65, a marker for GABAergic terminals, and for subunits of
      IGRs to test directly whether IGRs are expressed in GABAergic terminals in
      laminae I-III of the dorsal horn. Although colocalization is hard to detect with
      confocal microscopy, electron microscopy reveals a substantial number of
      terminals immunoreactive for GAD65 also stained for IGRs. Among all GAD65
      immunoreactive terminals counted, 37% express the NMDA receptor subunit NR1; 28%
      are immunopositive using an antibody for the GluR2/4 subunits of the AMPA
      receptor; and 20-35% are immunopositive using antibodies for the kainate receptor
      subunits GluR5, GluR6/7, KA1, or KA2. Terminals immunoreactive for IGR subunits
      and GAD65 establish symmetric synapses onto dendrites and perikarya and can be
      presynaptic to primary afferent terminals within both type 1 and type 2 synaptic
      glomeruli. Activation of presynaptic IGR may reduce neurotransmitter release. As
      autoreceptors in terminals of Adelta and C afferent fibers in laminae I-III,
      presynaptic IGRs may play a role in inhibiting nociception. As heteroreceptors in
      GABAergic terminals in the same laminae, on the other hand, presynaptic IGRs may
      have an opposite role and even contribute to central sensitization and
      hyperalgesia.

PMID- 15844210
TI  - Descending projections from the auditory cortex to the inferior colliculus in the
      gerbil, Meriones unguiculatus.
AB  - Corticofugal projections to the auditory midbrain, the inferior colliculus (IC),
      influence the way in which specific sets of IC neurons process acoustic signals.
      We used retrograde tracer (Fluorogold, Fluororuby, microbeads) injections in the
      IC to study the morphology and location of cortico-collicular projecting neurons
      and anterograde tracer (dextran biotin) injections in auditory cortical fields to
      describe the distribution of terminals in the IC. Nissl staining, cytochrome
      oxidase activity, and neurofilament SMI32 immunostaining were used to delimit the
      different auditory areas. We defined a primary or "core" auditory cortex and a
      secondary "caudal" auditory area containing layer V pyramidal neurons that
      project to the IC. These projections target the central nucleus of the IC (CNIC)
      ipsilaterally and the IC cortices bilaterally, with the ipsilateral component
      predominant. Other secondary auditory areas, dorsal and ventral to the core, do
      not directly participate in this projection. The ventral secondary cortex targets
      midbrain periaqueductal gray. The projection from the core cortex originates from
      two classes of layer V pyramidal cells. Cells presenting a tufted apical dendrite
      in layer I have dense terminal fields in the IC cortices. Pyramids lacking layer
      I dendritic tufts target the CNIC in a less dense but tonotopic manner. The
      caudal cortex projection originates from smaller layer V pyramids and targets the
      IC cortices with dense terminal fields. Descending auditory inputs from the core
      and caudal areas converge in the dorsal and external cortices of the IC.
      Descending connections to the gerbil IC form a segregated system in which
      multiple descending channels originating from different neuronal subpopulations
      may modulate specific aspects of ascending auditory information.

PMID- 15844212
TI  - Inferior olivary neurons innervate multiple zones of the flocculus in pigeons
      (Columba livia).
AB  - Complex spike activity of floccular Purkinje cells responds to patterns of
      rotational optic flow about the vertical axis (rVA neurons) or a horizontal axis
      45 degrees to the midline (rH45 neurons). The pigeon flocculus is organized into
      four parasagittal zones: two rVA zones (zones 0 and 2) interdigitated with two
      rH45 zones (zones 1 and 3). Climbing fiber input to the rVA and rH45 zones arises
      in the caudal and rostral regions of the medial column of the inferior olive
      (mcIO), respectively. To determine whether the two rVA zones and the two rH45
      zones receive input from different areas of the caudal and rostral mcIO and
      whether individual neurons project to both zones of the same rotational
      preference, different colors of fluorescent retrograde tracer were injected into
      the two rVA or two rH45 zones. For the rVA injections, retrogradely labeled cells
      from the two zones were intermingled in the caudal mcIO, but the distribution of
      cells labeled from zone 0 was slightly caudal to that from zone 2. On average,
      18% of neurons were double labeled. For the rH45 injections, cells retrogradely
      labeled from the two zones were intermingled in the rostral mcIO, but the
      distribution of cells labeled from zone 1 was slightly rostral to that from zone
      3. On average, 22% of neurons were double labeled. In sum, each of the two rVA
      zones and the two rH45 zones receives input from slightly different regions of
      the mcIO, and about 20% of the neurons project to both zones.

PMID- 15844211
TI  - Morphological and biochemical heterogeneity in facial and vagal nerve innervated
      taste buds of the channel catfish, Ictalurus punctatus.
AB  - In catfish, the facial nerve innervates taste buds distributed over the entire
      body including the barbels, while the glossopharyngeal and vagal nerves innervate
      oropharyngeal taste buds. Facial nerve innervated taste buds (FITBs) are thought
      to be involved in food detection and localization, while glossopharyngeal and
      vagal nerve innervated taste buds (VITBs) evaluate the palatability of food prior
      to ingestion. Physiological studies indicate that both oral and extra-oral taste
      buds detect sapid substances such as amino acids and nucleotides, but the facial
      taste system is more sensitive to some of these substances. The anatomical,
      molecular, and/or physiological mechanisms underlying the functional differences
      in these two gustatory pathways remain to be identified. In the current
      investigation we compare the basic morphological features of FITBs and VITBs and
      the distribution of the following metabolites: gamma-aminobutyric acid (GABA),
      glutamate, aspartate, alanine, taurine, and glutathione. Vagal innervated taste
      buds are significantly longer and narrower than FITBs, with fewer taste cells and
      a smaller nerve plexus. Each of the metabolites examined was heterogeneously
      distributed in taste cells with notably more GABA positive cells present in the
      VITBs. Patterns of metabolite colocalization suggest the presence of several
      taste cell subtypes. The morphological and metabolite differences noted between
      FITBs and VITBs provide a potential anatomical basis for the previously noted
      differences in physiological sensitivity.

PMID- 15844213
TI  - Expression and distribution of TTX-sensitive sodium channel alpha subunits in the
      enteric nervous system.
AB  - The expression and distribution of TTX-sensitive voltage-gated sodium channel
      (VGSC) alpha subunits in the enteric nervous system (ENS) has not been described.
      Using RT-PCR, expression of Na(v)1.2, Na(v)1.3, Na(v)1.6, and Na(v)1.7 mRNA was
      detected in small and large intestinal preparations from guinea pigs. Expression
      of Na(v)1.1 mRNA as well as Na(v)1.1-like immunoreactivity (-li) were not
      observed in any intestinal region investigated. Na(v)1.2-li was primarily
      observed within the soma of the majority of myenteric and submucosal neurons,
      although faint immunoreactivity was occasionally observed in ganglionic and
      internodal fibers. Na(v)1.3-li was observed in dendrites, soma, and axons in a
      small group of myenteric neurons, as well as in numerous myenteric internodal
      fibers; immunoreactivity was rarely observed in the submucosal plexus. Na(v)1.6
      li was primarily observed in the initial axonal segment of colonic myenteric
      neurons. Na(v)1.7-li was observed in dorsal root ganglia neurons but not in the
      myenteric plexus of the small and large intestine. In the ileum, 37% of Na(v)1.2
      li cell bodies colocalized with calbindin-li while colocalization with calretinin
      li was rare. In contrast, 22% of Na(v)1.3-li cell bodies colocalized with
      calretinin-li but colocalization with calbindin-li was not observed. In the
      colon, both Na(v)1.2-li and Na(v)1.3-li cell bodies frequently colocalized with
      either calretinin-li or calbindin-li. Na(v)1.2-li cell bodies also colocalized
      with the majority of NeuN-li cells in the small and large intestine. These data
      suggest that Na(v)1.1 may not be highly expressed in the ENS, but that Na(v)1.2,
      Na(v)1.3, and Na(v)1.6, and possibly Na(v)1.7, have broadly important and
      distinct functions in the ENS.

PMID- 15844214
TI  - Increased expression of MDM2, cyclin D1, and p27Kip1 in carcinogen-induced rat
      mammary tumors.
AB  - It is thought that environmental pollutants, such as polycyclic aromatic
      hydrocarbons (PAH), contribute to human breast tumorigenesis, yet their roles
      remain incompletely elucidated. The prototypical PAH 7,12
      dimethylbenz(alpha)anthracene (DMBA) specifically and effectively induces mammary
      tumor formation in rodent models. In an attempt to explore the molecular
      mechanisms by which PAH initiates and promotes mammary tumorigenesis, we examined
      the expression of several cell cycle regulators in rat mammary tumors induced by
      DMBA. Expression of cyclin D1, murine double minute-2 (MDM2), and Akt was up
      regulated in tumors in comparison to normal mammary glands, as indicated by RT
      PCR, Western blot analysis, and immunohistochemical staining. Expression of
      p27Kip1 protein was also elevated in the tumors with increased cytoplasmic
      localization. However, RB protein remained hyperphosphorylated. To directly test
      the effects of DMBA, the MCF-7 human breast cancer cells were treated. DMBA
      induced MDM2 expression in a dose- and time-dependent fashion in the MCF-7 cells,
      and this activation appeared to be p53 dependent. These data suggest that
      activation of cyclin D1, MDM2, and AKT as well as increased expression and
      cytoplasmic localization of p27Kip1 may play a role in this model of
      environmental pollutant-induced mammary tumorigenesis.

PMID- 15844215
TI  - Anti-infectives-induced adverse drug reactions in hospitalized patients.
AB  - OBJECTIVES: To assess the rate and seriousness of adverse drug reactions (ADRs)
      attributable to anti-infective agents in hospitalized patients; to estimate the
      likelihood of experiencing anti-infectives-induced ADRs at different length of
      drug usage in the hospital; to compare different classes of anti-infectives in
      inducing ADRs; to determine the impact of age and sex on anti-infectives-induced
      ADRs. DESIGN: Prospective cohort study. PARTICIPANTS: Patients admitted to the
      infectious diseases department at a university teaching hospital, on Sunday to
      Wednesday, over a 9 months period, who received at least one anti-infective agent
      were eligible to enter the study. MAIN OUTCOME MEASURES: Any suspected noxious
      and untoward medical events, including laboratory tests abnormalities following
      anti-infective therapy. METHODS: All patients admitted have received at least one
      anti-infective drug. Anti-infective agents induced ADRs were detected by
      interviewing patients and daily chart review. The seriousness, causality, and
      type of reactions were classified based on World Health Organization (WHO)
      definitions. Chi-square analysis was performed to assess the influence of sex and
      age on occurring ADRs. Both Kaplan-Meier and life table method were used to
      estimate the time to occur the ADR in anti-infective users. To compare the
      estimated risk of ADRs induced by different classes of anti-infectives, odds
      ratios were estimated. In all classes of anti-infectives, the odds ratio of each
      class was estimated with regard to anti-tuberculosis agents, which had the
      highest prevalence of ADRs. RESULTS: During the study period, 460 patients were
      entered the study. During the same period, 38 ADRs were recognized of which 20
      (42%) were serious. The most recognized ADRs were suspected to be induced by anti
      tuberculosis agents (29.8%). However in comparing with anti-tuberculosis agents,
      anti-fungal agents were associated with the highest ADR rate (odds ratio [OR],
      4.21; 95% confidence interval [CI], 1.41-1.256) whereas cephalosporines were
      associated with the lowest rate, (OR, 0.1; 95%CI, 0.04-0.26). The survival
      analysis shows that the likelihood of experiencing an ADR was increased at first
      14 days of drug therapy. Also Chi-square analysis shows that greater risk of anti
      infectives-induced ADRs was observed in women. CONCLUSION: The rate of ADRs
      induced by anti-infective agents in this study was 8.2%. This is higher than a
      standard (5%) which has been reported in other studies. This study also shows
      that some of the classes of anti-infective agents like anti-fungals need more
      attention.

PMID- 15844216
TI  - Apoptosis and release of CD44s in bleomycin-treated L132 cells.
AB  - The anti-cancer drug bleomycin (BLM) induces lung injury and triggers apoptosis
      of alveolar epithelial cells. In epithelia, among other functions, the adhesion
      protein CD44 promotes the contact to components of the extracellular matrix like
      hyaluronate. A functional link between apoptosis and the loss of CD44 has been
      observed in colon carcinoma cells and involvement of CD44 in apoptosis of lung
      cells has been reported in several studies. The present in vitro study examined
      the expression of CD44s (CD44 standard) in two human epithelial lung cell lines,
      L132 and A549, during BLM-induced apoptosis. A loss of CD44s by lung epithelial
      cells and an increase of the soluble form of this adhesion protein in culture
      supernatants upon exposure to BLM were observed. Apoptosis was characterized by
      an activation of caspase-3 as well as by release of cytochrome C into the cytosol
      as shown for L132 cells. Inhibition of apoptosis by the broad-range caspase
      inhibitor Z-VAD-fmk reduced CD44 release by both cell lines demonstrating that
      CD44 release is a result of apoptotic processes. Kinetic experiments failed to
      discriminate between the initiation of apoptosis and CD44 release. Blocking
      experiments using antagonistic anti-CD95 receptor antibodies revealed that BLM
      may cause apoptosis and CD44 release in a CD95-independent manner.

PMID- 15844217
TI  - Supramolecular order following binding of the dichroic birefringent sulfonic dye
      Ponceau SS to collagen fibers.
AB  - The optical anisotropies (linear dichroism or LD and birefringence) of
      crystalline aggregates of the sulfonic azo-dye Ponceau SS and of dye complexed
      with chicken tendon collagen fibers were investigated in order to assess their
      polarizing properties and similarity to liquid crystals. In some experiments, the
      staining was preceded by treatment with picric acid. Crystalline fibrous
      aggregates of the dye had a negative LD, and their electronic transitions were
      oriented perpendicular to the filamentary structures. The binding of Ponceau SS
      molecules to the collagen fibers altered the LD signal, with variations in the
      fiber orientation affecting the resulting dichroic ratios. The long axis of the
      rod-like dye molecule was assumed to be bound in register, parallel to the
      collagen fiber. Picric acid did not affect the oriented binding of the azo dye to
      collagen fibers. There were differences in the optical anisotropy of Ponceau SS
      stained tendons from 21-day-old and 41-day-old chickens, indicating that Ponceau
      SS was able to distinguish between different ordered states of macromolecular
      aggregation in chicken tendon collagen fibers. In the presence of dichroic rod
      like azo-dye molecules such as Ponceau SS, collagen also formed structures with a
      much higher degree of orientation. The presence of LD in the Ponceau SS-collagen
      complex even in unpolarized light indicated that this complex can act as a
      polarizer.

PMID- 15844219
TI  - Fees. State not liable for attorney's fees in failed HIV prosecution.

PMID- 15844218
TI  - A new insight into PMM2 mutations in the French population.
AB  - Congenital disorder of Glycosylation type Ia is an autosomal recessive disorder,
      characterized by a central nervous system dysfunction and multiorgan failure
      associated with defective N-glycosylation and phosphomannomutase (PMM) deficiency
      related to mutations in the PMM2 gene (mRNA U85773.1, gene ID 5373). More than 75
      different mutations have been previously described. In our study, 38 different
      mutations were found in 52 French families with CDG-Ia. Eleven mutations had not
      been previously published in CDG-Ia patients: eight missense and three splice
      mutations. We studied the PMM activity of eight novel recombinant mutant proteins
      in an E. coli expression system, comparing them with the wild type protein, c.422
      G>A (R141H), and c.415 G>A (E139K) mutant proteins. We also studied the
      previously described c.590 C>A (E197A) found on the same allele as c.394 A>T
      (I132F). All mutant proteins studied except E197A had decreased activity and/or
      were thermolabile, and were pathogenic mutations. Haplotype studies revealed a
      founder effect for E139K mutation, only described in France and found in seven
      CDG-Ia families (7.6%). In contrast, at least two different haplotypes were
      observed for the R141H mutation in France, studied in 23 families. The R141H
      seems to be a combination of the "old" R141H mutation found all over Europe and a
      second "French" R141H, and could be substantially older than E139K.

PMID- 15844220
TI  - Prevention. Antibody that neutralizes most HIV strains discovered.

PMID- 15844221
TI  - Prisons. Inmate's fear of HIV exposure survives dismissal.

PMID- 15844222
TI  - Sick leave inquiries that violated ADA might be justified.

PMID- 15844223
TI  - Criminal exposure. Man's AIDS admission was not a factor in sentencing.

PMID- 15844224
TI  - FDA issues final guidance on nucleic acid tests.

PMID- 15844225
TI  - I recently suffered a heart attack and want to make sure it's safe to exercise.
      If so, what type of exercise do you recommend?

PMID- 15844227
TI  - Treatment targets mutant strains.

PMID- 15844226
TI  - Jeffrey Sachs' "punk-rock" appeal to the Nobel committee.

PMID- 15844228
TI  - Resistance with short-course nevirapine.

PMID- 15844230
TI  - Early detection vs late treatment of amblyopia.

PMID- 15844231
TI  - Structure-function relationships in the growing hexa-coordinate hemoglobin sub
      family.
AB  - Hemoglobin and related heme proteins, generally referred to as 'globins',
      reversibly bind gaseous diatomic ligands (O2, NO, and CO) to a penta-coordinate
      heme iron atom, the ligand filling the sixth coordination site. Over the last
      decade, several new globins have been reported to display a functionally-relevant
      hexa-coordinate heme iron atom, whose sixth coordination site is taken by an
      endogenous protein ligand. The reversible intramolecular hexa- to penta
      coordination process at the heme-Fe atom modulates exogenous ligand binding
      properties of hexa-coordinate globins. Here, we review current knowledge on hexa
      coordinate globins in terms of their structural and functional properties.

PMID- 15844232
TI  - [Respiration. Extract from the first "Cultural Dictionary in the French Language"
      from Robert's Dictionary].

PMID- 15844229
TI  - Practical uses for ecdysteroids in mammals including humans: an update.
AB  - Ecdysteroids are widely used as inducers for gene-switch systems based on insect
      ecdysteroid receptors and genes of interest placed under the control of
      ecdysteroid-response elements. We review here these systems, which are currently
      mainly used in vitro with cultured cells in order to analyse the role of a wide
      array of genes, but which are expected to represent the basis for future gene
      therapy strategies. Such developments raise several questions, which are
      addressed in detail. First, the metabolic fate of ecdysteroids in mammals,
      including humans, is only poorly known, and the rapid catabolism of ecdysteroids
      may impede their use as in vivo inducers. A second set of questions arose in fact
      much earlier with the pioneering "heterophylic" studies of Burdette in the early
      sixties on the pharmacological effects of ecdysteroids on mammals. These and
      subsequent studies showed a wide range of effects, most of them being beneficial
      for the organism (e.g. hypoglycaemic, hypocholesterolaemic, anabolic). These
      effects are reviewed and critically analysed, and some hypotheses are proposed to
      explain the putative mechanisms involved. All of these pharmacological effects
      have led to the development of a wide array of ecdysteroid-containing
      preparations, which are primarily used for their anabolic and/or "adaptogenic"
      properties on humans (or horses or dogs). In the same way, increasing numbers of
      patents have been deposited concerning various beneficial effects of ecdysteroids
      in many medical or cosmetic domains, which make ecdysteroids very attractive
      candidates for several practical uses. It may be questioned whether all these
      pharmacological actions are compatible with the development of ecdysteroid
      inducible gene switches for gene therapy, and also if ecdysteroids should be
      classified among doping substances.

PMID- 15844233
TI  - Experimental drug quickly suppresses HIV.

PMID- 15844234
TI  - Possible HIV "super-strain" in New York City; new human T-lymphotropic viruses
      identified in Africa.

PMID- 15844235
TI  - Policy watch. Is an ownership society progress?

PMID- 15844236
TI  - AIDS policy, politics, and law: reflections on the pandemic.

PMID- 15844237
TI  - Insulin resistance, HIV infection, and anti-HIV therapies.
AB  - Insulin resistance, a risk factor for cardiovascular disease, is increasingly
      seen in persons infected with HIV. In those affected, it is unclear whether
      insulin resistance is a direct result of HIV infection alone; however, the
      development of insulin resistance has been established as a complication of
      antiretroviral therapies. Some protease inhibitors (PIs) are culpable, and there
      are significant differences in the impact of different PIs on glucose metabolism,
      with current evidence suggesting that atazanavir does not cause insulin
      resistance. The paucity of standardized laboratory tests makes early diagnosis of
      insulin resistance relatively elusive. Still, there are some clinically useful
      methods for assessing its presence. For prevention and/or treatment, exercise and
      optimal diet are useful, and metformin and rosiglitazone have been shown to
      improve insulin resistance. Changing an effective antiretroviral regimen to
      counter insulin resistance must be approached thoughtfully in carefully selected
      patients.

PMID- 15844239
TI  - Editorial comment: failure of HAART to reconstitute CMV-specific protective
      immunity.

PMID- 15844238
TI  - Cytomegalovirus retinitis after immune reconstitution.
AB  - Cytomegalovirus (CMV) infection is the most common opportunistic infection that
      affects the retina in HIV-positive patients; it typically occurs in the setting
      of severe immune suppression (CD4 count less than 50 cell/microL). We present a
      case report of an HIV-infected patient in whom recurrent CMV retinitis developed
      after HAART and apparent immune reconstitution (CD4 count of greater than 500
      cells/microL). This case report underscores that CMV infection may occur despite
      high CD4 counts among patients who experience only partial immune reconstitution.

PMID- 15844240
TI  - Kaposi sarcoma flares during effective antiretroviral treatment.

PMID- 15844241
TI  - Find out about the side effects of your prescription drugs. Here's how to locate
      the information--and how to make sense of what you find.

PMID- 15844242
TI  - Asthma: grown-ups have it, too. The condition is sometimes misdiagnosed in
      adults, although proper treatment could spare many bouts of coughing and
      wheezing.

PMID- 15844243
TI  - When teeth get damaged. Take quick action and you could save the tooth a root
      canal may be unavoidable, but (honest!) it shouldn't be that painful.

PMID- 15844244
TI  - Travelers: sites to see before you go.

PMID- 15844245
TI  - By the way, doctor. Ever since the 1960s, I haven't eaten more than one egg a
      week because egg yolks have a lot of cholesterol. Now my wife says she heard on
      the news that it's okay to eat eggs every day. What do you think?

PMID- 15844246
TI  - What to do when allergic rhinitis is in bloom. It's that time of year again. Some
      of the most irritating allergies are ready to spring into action.

PMID- 15844247
TI  - When a breast cancer expert gets breast cancer. An interview with Harvard breast
      cancer surgeon Dr. Carolyn Kaelin.

PMID- 15844248
TI  - How to spell pain relief in the wake of COX-2 problems. Taking drugs of any kind
      is never without risks, but recent news about the vigorously marketed COX-2
      inhibitors has really brought this home.

PMID- 15844249
TI  - By the way, doctor. I wake up at night with pins and needles in one or both of my
      hands. I've tried chiropractic, physical therapy, and a special pillow, with no
      success. What's causing this, and what can I do to stop it?

PMID- 15844250
TI  - Research on Alzheimer's caregiving in Canada: current status and future
      directions.
AB  - In December 2002, a national workshop was held in Ottawa to guide research
      directions for the caregiving of people with Alzheimer's disease in Canada. Prior
      to the workshop, a search was conducted to identify Canadian-based investigators
      who have conducted research related to caregiving of individuals with cognitive
      impairment, Alzheimer's disease and other dementia, identify relevant Canadian
      research studies, and provide an overview of results and themes emerging from
      this research. This paper summarizes findings from our search for Canadian
      studies, research themes identified at the national workshop in Ottawa, and
      recommendations from the workshop. The report first outlines patterns of
      caregiving and subsequently focusses on the impact of different ways of assisting
      Alzheimer's caregivers. It concludes by outlining the methodological challenges
      of observational and intervention studies related to Alzheimer's caregiving and
      recommendations on how to increase Canada's capacity to conduct research on
      Alzheimer's caregiving.

PMID- 15844251
TI  - Gains and losses of HLA class II (DR) and CD4 in atypical hyperplasia, carcinoma
      in situ and infiltrating ductal carcinoma of the breast.
AB  - AIM: Breast cancer is a frequent cause of death among women with gynaecologic
      malignancies despite the introduction of combination chemotherapy. There is
      therefore a need for new therapeutic strategies for patients with breast cancer,
      such as cellular immunotherapy. In this immunohistochemical study we analyzed the
      epithelial expression of major histocompatibility complex (MHC) class II (HLA-DR)
      on atypical and malignant primary mammary epithelial cells, as well as the
      magnitude of the stromal T lymphocytes (T4 subset) at the tumor site.
      EXPERIMENTAL DESIGN: The study was carried out retrospectively in tumor tissue
      from 82 patients with mammary lesions (31 cases of atypical ductal hyperplasia 
      ADH-, 12 cases of ductal carcinoma in situ -DCIS- and 39 cases of infiltrating
      ductal carcinoma not otherwise specified -IDC-NOS). Medullary carcinomas were not
      included in our investigation. Material used had been formalin fixed and paraffin
      embedded. RESULTS: HLA class II (DR) was expressed in 20 of 31 ADHs (64.5%), in 4
      of 12 DCISs (33.3%), and in 10 of 39 IDC-NOSs (25.6%). CD4 was expressed in 9 of
      31 ADHs (29%), in 5 of 12 DCISs (42%), and in 26 of 39 IDC-NOSs (67%).
      CONCLUSIONS: The results showed decreased epithelial expression of HLA class II
      (DR) and increased stromal expression of CD4, as the lesion progressed to
      malignancy. Gradual loss of epithelial HLA class II expression might be a
      manifestation of cellular differentiation from the atypical form versus the
      malignant one, signaling simultaneously a selective effect on the response
      capacity of the immune system.

PMID- 15844252
TI  - Differences in delta13C and delta15N of particulate organic matter from the deep
      oligotrophic Lake Fuxian connected with the shallow eutrophic Lake Xingyun,
      People's Republic of China.

PMID- 15844253
TI  - Retraction. Growth inhibiting effects of terazosin on androgen-independent
      prostate cancer cell lines.

PMID- 15844254
TI  - Recent progress in molecular genetics and cytogenetic investigations for early
      prenatal and postnatal diagnosis. Proceedings of the 14th Workshop on Fetal Cells
      and Fetal DNA. April 17-18, 2004. Jena, Germany.

PMID- 15844256
TI  - Abstracts of SCANNING 2005. April 5-7, 2005, Monterey, California, USA.

PMID- 15844255
TI  - Intracellular parasitism: biology and pathogenesis. Proceedings of the 2nd
      International Conference. October 22-23, 2004.

PMID- 15844257
TI  - Canadian Society of Otolaryngology--Head and Neck Surgery 2004/2005 membership
      guide.

PMID- 15844258
TI  - Abstracts of the 18th International Conference on Antiviral Research. Barcelona,
      Spain, April 11-14, 2005.

PMID- 15844259
TI  - Organic dusts and disease: a continuous research challenge. Selected papers from
      the 4th Skokloster Workshop: Organic Dusts-Agents, Disease and Prevention. April
      7-10, 2003. Gothenburg, Sweden.

PMID- 15844260
TI  - Abstracts from the Association for Veterinary Teaching and Research Work Current
      Topics in Veterinary Science 59th Annual Conference. Scarborough, United Kingdom,
      21-23 March 2005.

PMID- 15844261
TI  - [Diabetes--Lyon 2005. Abstracts of Alfediam and Alfadiam Paramedical meeting. 22
      26 March 2005, Lyon, France].

PMID- 15844262
TI  - Abstracts from the 26th Annual Meeting of the American Society for Apheresis.
      April 27-30, 2005, Chicago, Illinois, USA.

PMID- 15844263
TI  - [Promotion of classification of prosthodontic disorders in edentulous patients].

PMID- 15844264
TI  - ISB recommendation on definitions of joint coordinate systems of various joints
      for the reporting of human joint motion--Part II: shoulder, elbow, wrist and
      hand.
AB  - In this communication, the Standardization and Terminology Committee (STC) of the
      International Society of Biomechanics proposes a definition of a joint coordinate
      system (JCS) for the shoulder, elbow, wrist, and hand. For each joint, a standard
      for the local axis system in each articulating segment or bone is generated.
      These axes then standardize the JCS. The STC is publishing these recommendations
      so as to encourage their use, to stimulate feedback and discussion, and to
      facilitate further revisions. Adopting these standards will lead to better
      communication among researchers and clinicians.

PMID- 15844265
TI  - [Selection of occlusal scheme for complete dentures].

PMID- 15844266
TI  - [Selection and establishment criteria for occlusal form in complete dentures].

PMID- 15844267
TI  - [Criteria for the selection of the complete denture occlusion].

PMID- 15844268
TI  - [Is lingualized occlusion appropriate?].

PMID- 15844269
TI  - ["Truth" in the lingualized occlusion].

PMID- 15844271
TI  - Abstracts of the 13th Association of European Psychiatrists Congress. Munich,
      Germany, 2-6 April 2005.

PMID- 15844270
TI  - [Full-balanced occlusion or lingualized occlusion?--A critical review].

PMID- 15844272
TI  - The stationary phase and chromatographic retention. Festschrift in honor of J.J.
      Kirkland.

PMID- 15844273
TI  - ABRF 2005. Biomolecular technologies: discovery to hypothesis.  February 5-8,
      2005, Savannah, Georgia, USA. Abstracts.

PMID- 15844274
TI  - Abstracts of the Annual Conference of the British Association of Sport and
      Exercise Sciences. 7-9 September 2004, Liverpool, United Kingdom.

PMID- 15844275
TI  - The effect of health savings accounts on health insurance coverage.
AB  - The authors investigate the potential of Health Savings Accounts (HSAs) to expand
      health insurance coverage. They examine how many currently uninsured people might
      be encouraged to buy coverage through HSAs, and what the impacts of such actions
      might be on the group and nongroup health insurance markets. Their main
      conclusions: HSAs are not likely to be an important contributor to expanding
      coverage among uninsured people because most of them do not face high-enough
      marginal tax rates to benefit substantially from the tax deductibility of HSA
      contributions. Meanwhile, HSAs could potentially destabilize the small-group
      market. To the extent that they encourage well-compensated healthy workers to
      abandon job-based coverage--a result that is more likely if current HSA
      provisions are combined with proposed premium deductibility--HSAs could undermine
      the entire structure of job-based coverage among small firms.

PMID- 15844276
TI  - Festschrift dedicated to David M. Jacobowitz.

PMID- 15844278
TI  - Proceedings of the Mediterranean Academy of Forensic Sciences (MAFS) First
      Workshop. June 10-13, 2004. Isola Capo Rizzuto, Italy.

PMID- 15844277
TI  - [The focused assessment of trauma using ultrasonography (FAST)].

PMID- 15844279
TI  - A ride on the ferrous wheel.

PMID- 15844282
TI  - Population screening and patient testing using PSA.

PMID- 15844283
TI  - Part 1: The burden of prostate cancer, its natural history, information on the
      outcome of screening and estimates of ad hoc screening with particular reference
      to England and Wales.

PMID- 15844284
TI  - Part 2: Patient information, informed decision-making and the psycho-social
      impact of prostate-specific antigen testing.

PMID- 15844286
TI  - A national strategy for smoking cessation treatment in England.
AB  - In 1998 the UK government published a White Paper on tobacco which set out the
      development of smoking cessation treatment services across England. This paper
      presents a detailed analysis of the events leading up to the inclusion of smoking
      cessation treatment services within the White Paper, and the background to the
      evaluation of those services, the results of which are the subject of the
      remaining papers in this supplement.

PMID- 15844285
TI  - Automorphosis of etiolated pea seedlings in space is simulated by a  three
      dimensional clinostat and the application of inhibitors of auxin  polar
      transport.
AB  - Etiolated pea (Pisum sativum L. cv. Alaska) seedlings grown under microgravity
      conditions in space show automorphosis: bending of epicotyls, inhibition of hook
      formation and changes in root growth direction. In order to determine the
      mechanisms of microgravity conditions that induce automorphosis, we used a three
      dimensional clinostat and obtained the successful induction of automorphosis-like
      growth of etiolated pea seedlings. Kinetic studies revealed that epicotyls bent
      at their basal region towards the clockwise direction far from the cotyledons
      from the vertical line (0 degrees) at approximately 40 degrees in seedlings grown
      both at 1 g and in the clinostat within 48 h after watering. Thereafter,
      epicotyls retained this orientation during growth in the clinostat, whereas those
      at 1 g changed their growth direction against the gravity vector and exhibited a
      negative gravitropic response. On the other hand, the plumular hook that had
      already formed in the embryo axis tended to open continuously by growth at the
      inner basal portion of the elbow; thus, the plumular hook angle initially
      increased; this was followed by equal growth on the convex and concave sides at 1
      g, resulting in normal hook formation; in contrast, hook formation was inhibited
      on the clinostat. The automorphosis-like growth and development of etiolated pea
      seedlings was induced by auxin polar transport inhibitors (9-hydroxyfluorene-9
      carboxylic acid, N-(1-naphthyl)phthalamic acid and 2,3,5-triiodobenzoic acid),
      but not by anti-auxin (p-chlorophenoxyisobutyric acid) at 1 g. An ethylene
      biosynthesis inhibitor, 1-aminooxyacetic acid, inhibited hook formation at 1 g,
      and ethylene production of etiolated seedlings was suppressed on the clinostat.
      Clinorotation on the clinostat strongly reduced the activity of auxin polar
      transport of epicotyls in etiolated pea seedlings, similar to that observed in
      space experiments (Ueda J, Miyamoto K, Yuda T, Hoshino T, Fujii S, Mukai C,
      Kamigaichi S, Aizawa S, Yoshizaki I, Shimazu T, Fukui K (1999) Growth and
      development, and auxin polar transport in higher plants under microgravity
      conditions in space: BRIC-AUX on STS-95 space experiment. J Plant Res 112:
      487492). These results suggest that clinorotation on a three-dimensional
      clinostat is a valuable tool for simulating microgravity conditions, and that
      automorphosis of etiolated pea seedlings is induced by the inhibition of auxin
      polar transport and ethylene biosynthesis.

PMID- 15844287
TI  - Implementing a national treatment service for dependent smokers: initial
      challenges and solutions.
AB  - BACKGROUND: Before 1999, few treatment services for nicotine-addicted smokers
      existed in England. When national treatment services were introduced, those
      responsible for setting them up liaised closely with primary care health
      services. Setting up an entirely new national service, treating a new category of
      patient (smokers motivated to stop) was an ambitious aim and this paper documents
      the problems encountered in the early stages of this process. OBJECTIVES: To
      describe the principal challenges encountered and solutions employed by those
      setting up the services during the initial period of smoking cessation service
      implementation. METHODS: Qualitative, semistructured interviews with 50 smoking
      cessation staff in two former English health regions conducted in autumn 2001.
      FINDINGS: Two principal factors which slowed the initial development of smoking
      cessation services were: (i) the lack of a work-force with experience in smoking
      cessation methods and (ii) the fact that services were set up outside existing
      primary and secondary care health services in England. As few training courses in
      smoking cessation were available, many services provided their own in-house
      training for staff appointed as smoking cessation advisers. Consequently, senior
      service staff devoted a lot of effort to training new staff which meant that they
      had less time to spend on other important tasks which were necessary for service
      implementation. Smoking cessation services needed to develop relationships with
      primary care health services in order to generate referrals and find venues for
      the delivery of smoking cessation interventions. Liaising with primary care
      physicians was time-consuming, however, and some primary care physicians were
      opposed to the ideas that service staff had for the interface between primary
      care and smoking cessation services. As new smoking cessation services were not
      set up within existing primary or secondary health care services, service staff
      had to spend large amounts of time on this process of negotiation and overcoming
      scepticism from some primary health care physicians. CONCLUSIONS: If smoking
      cessation services are set up in other countries, rapid implementation would be
      facilitated by ensuring that adequate numbers of health professionals trained in
      smoking cessation methods are available to staff services. Additionally, locating
      new smoking cessation services within existing health providers' services may
      speed up service implementation, but this option may not suit all health systems.

PMID- 15844288
TI  - Delivering the English smoking treatment services.
AB  - BACKGROUND: This paper describes how smoking treatment services in England were
      delivered beyond the initial set-up phase and explores key factors affecting
      their development. Services were expected to treat smokers in line with the
      evidence-base and were issued with government guidance regarding the type of
      interventions that should be offered. One factor complicating this was the issue
      of service funding. Funding was initially issued for a 3-year period and although
      this was extended on two occasions, these extensions were both announced close to
      the end of funding periods. OBJECTIVES: To critically assess key elements in the
      delivery of the English cessation services, including the nature of treatments
      offered and the impact of short-term funding on staffing. METHODS: A national
      postal survey of smoking cessation coordinators in April 2002. Semi-structured
      interviews with 50 smoking cessation staff in two health regions in autumn 2001,
      followed by further interviews with 28 staff in the same areas in the autumn of
      2002. RESULTS: Treatment was delivered in a wide range of venues, ranging from
      primary care to local authority-owned premises such as town halls and libraries.
      Most services offered both one-to-one and group support, although interviewees
      reported an increase in demand for one-to-one support from clients.
      Pharmacotherapies were used widely; by 2002, 99% of coordinators reported that
      their advisers recommended nicotine replacement therapy (NRT) to clients, and 95%
      bupropion. However, prior to April 2001 bupropion was available on prescription,
      but NRT was not and this variable access to pharmacotherapies posed problems for
      services. Coordinators reported that the short-term nature of funding made
      recruiting and retaining staff difficult and interviews revealed that they
      believed a longer period of protected funding was required for services to
      demonstrate their effectiveness. CONCLUSIONS: As English smoking treatment
      services developed, lessons were learned that could inform the development of
      services in other health systems. First, early guidance from government can
      encourage services to adhere to evidence-based treatment. Secondly, treatment
      needs to be accessible to smokers and thus there must be a flexible approach to
      implementation at local level. Thirdly, the availability of nicotine addiction
      and behavioural therapies should be coordinated to minimize barriers and maximize
      uptake. Finally, fixed-term funding can exacerbate staff recruitment and
      retention difficulties and countries establishing treatment services need to
      consider carefully the initial funding period that is required for stable
      services to become established within their health systems.

PMID- 15844289
TI  - The English smoking treatment services: short-term outcomes.
AB  - AIMS: To examine the impact of socio-demographic factors, smoking-related
      behaviour and service characteristics on CO-validated quit rates at 4-week follow
      up in English smoking treatment services, and to compare the results with those
      for self-reported quitters. DESIGN: Observational study of administrative
      information linked with survey data for 6959 recipients of smoking treatment
      services who set a quit date between October 2001 and March 2003. SETTING: Two
      contrasting areas of England, Nottingham and North Cumbria, consisting of nine
      primary care trust (PCT) localities. MEASUREMENTS: Routine monitoring data
      specified by the Department of Health included information about basic
      demographic characteristics, postcode of residence from which a deprivation
      category was identified, nature of intervention and smoking status at 4-week
      follow-up. These data were supplemented with additional information about
      referral pathways, socio-economic status and smoking-related behaviours obtained
      from consenting service recipients by NHS advisers. FINDINGS: More than one-half
      of clients (53%) were CO-validated as quitters at 4 weeks, rising to 60.7% when
      self-reported cases were included. Age (OR 1.026; CI 1.0221.029) and being
      extremely determined to quit (OR 1.46; CI 1.261.71) were associated positively
      with CO-validated cessation, whereas women (OR 0.85; CI 0.770.94), users with
      lower socio-economic status (OR 0.92; CI 0.880.95), those smoking 31 or more
      cigarettes daily (OR 0.75; CI 0.640.88) and those with relatively poor health
      status (OR 0.72; CI 0.630.82) were less likely to quit. Although the vast
      majority of users received one-to-one support, those who had group counselling
      were more likely to be successful in their quit attempt (OR 1.38; CI 1.091.76).
      Self-report and CO-validated quitters were similar in terms of their
      characteristics. CONCLUSIONS: These results obtained from routine services
      support those obtained from clinical trials and confirm the effectiveness of
      counselling combined with pharmacotherapies to assist smokers to quit in the
      short term. However, the relative effectiveness of group interventions raises
      questions about why one-to-one counselling is used much more commonly. The
      importance of socio-demographic and nicotine-related dependency factors also
      suggests that local service targets for smoking cessation need to take account of
      the social distribution of these characteristics.

PMID- 15844290
TI  - The cost-effectiveness of the English smoking treatment services: evidence from
      practice.
AB  - AIMS: To investigate the cost-effectiveness of English specialist smoking
      cessation services. DESIGN: Combination of observational cost and outcome data
      from English smoking cessation services to calculate cost-effectiveness ratios.
      Multivariate analysis of factors influencing variation in services' cost
      effectiveness. SETTING: Fifty-eight of the 92 specialist smoking cessation
      services in England in 2000/01. METHODS: Services' costs were estimated using
      survey data which described services' configurations, staffing, interventions
      delivered and development. Information on services' throughput and outcomes (as
      biochemically validated 4-week smoking cessation rates) were obtained from
      routine sources. With reference to relevant literature and assumptions about
      relapse and background cessation rates, 4-week cessation rates were converted
      first to 1-year rates. One-year cessation rates were adjusted to reflect the
      likely permanent smoking cessation rate attributable to service intervention and
      finally attributable life-years gained were calculated. A wide variety of
      sensitivity analyses was performed to test the robustness of the average cost
      effectiveness ratio, calculated by combining the cost and life-year gained
      estimates, for all services. With additional data on deprivation levels in
      services' areas, ordinary least-squares regression techniques were used to
      investigate variations in individual services' costs per client and cost
      effectiveness ratios. FINDINGS: Using an up-to-date estimate for health gain
      accrued by stopping smoking, the average cost per life gained was pound 684 (95%
      CI 557811), falling to pound 438 when savings in future health-care costs were
      counted. With the worst case assumptions, the estimate of cost-effectiveness rose
      to pound 2693 per life-year saved (pound 2293 including future health-care costs)
      and fell to pound 227 (pound 102) under the most favourable assumptions. Findings
      are comparable to previous published studies. The regression results suggest that
      different factors influence cost per client and the net cost per life-year saved,
      indicating that decision makers should be careful in setting performance targets
      for these services. CONCLUSIONS: In 2000/01, English smoking cessation services
      provided cost-effective services operating well below the benchmark of pound
      20,000 per quality-adjusted life-year saved (QALY) that is used by the National
      Institute for Clinical Excellence in the United Kingdom.

PMID- 15844291
TI  - Targeting smokers in priority groups: the influence of government targets and
      policy statements.
AB  - BACKGROUND: Cessation services were instructed to make special attempts to
      attract smokers from three 'priority groups': those who were young, pregnant and
      economically disadvantaged. Progress with attracting priority groups was not
      assessed formally, but services were set monitored targets to encourage
      throughput of smokers. Initial research suggests that services have been
      successful in attracting smokers who live in disadvantaged areas. This paper
      investigates how smoking cessation services responded to targets and instructions
      to attract priority groups and discusses the relative impact these on service
      development. OBJECTIVES: To describe how monitored throughput targets influenced
      the development of smoking cessation services, including attracting priority
      groups. To describe the range of priority groups that smoking cessation services
      targeted, methods used and reported progress with this. METHODS: Postal surveys
      of English smoking cessation coordinators conducted in April 2001 and April 2002.
      Seventy-eight qualitative, semistructured interviews with cessation service staff
      in two former English health regions conducted in autumn 2001 and 1 year later.
      FINDINGS: A total of 69.3% of coordinators responded to the first survey (79% to
      the second survey). In the first survey 91% reported targeting priority groups
      (100% in the second survey). The proportions (second survey in brackets) who
      reported targeting the different priority groups were: pregnant women 86% (99%),
      economically disadvantaged 79% (100%) and young smokers 20% (75%). Interviews
      showed that coordinators gave the greatest priority to reaching monitored targets
      as they came under pressure to achieve these. Service staff were generally
      unclear about how to attract priority groups and developing strategies for this
      was hindered by the need to meet throughput targets. Locating services in poor
      areas was thought to attract economically disadvantaged smokers and specialist
      staff were being appointed to work with pregnant smokers, but otherwise there was
      little evidence of active strategies for attracting priority groups being applied
      in practice. CONCLUSIONS: Monitored targets for smoker throughput ensured that
      services quickly began to treat smokers, but this rapid implementation diverted
      service staff from devising methods for attracting priority group smokers.
      Coordinators found reaching priority groups challenging and, particularly in the
      case of young smokers, would have appreciated clear instructions for this aspect
      of service implementation. Those implementing services in other countries should
      consider whether similar targets would be helpful to stimulate service
      development within their health systems.

PMID- 15844293
TI  - [Fidel warns against the health catastrophe that threatens the world].

PMID- 15844292
TI  - [Jubilee of Iuliia Semenovna Babenko (on the 80th year of her birth)].

PMID- 15844294
TI  - [Dr. Pedro Kouri Esmeja, Extraordinary Professor: on the centenary of his
      birthday (1900-2000)].

PMID- 15844295
TI  - [Synthesis of the speech delivered by Professor Gustavo Kouri on the centenary of
      the birthday of Professor Pedro Kouri Esmeja (1900-2000)].

PMID- 15844296
TI  - [A convinced Finlay's advocate--Pedro Kouri, Professor].

PMID- 15844298
TI  - [Infectious complications in cesarean section: previous classification and use of
      antibiotics].
AB  - A retrospective study of all the patients that underwent cesarean section at
      "Ramon Gonzalez Coro" Gynecoobstetric Hospital in 1997 and 1998 was made. The
      information about some variables, such as the diagnosis of cesarean sections, the
      frequency of infectious complications, the presence of complications according to
      the classification, the correct and incorrect use of antibiotics according to the
      classification of the surgical procedure and the occurrence of infectious
      complications due to the correct or incorrect use of antibiotics that were
      collected in the database of the Automated System to register cesarean sections
      was processed. The main indication was anterior cesarean section (34.1%),
      followed by cephalopelvic disproportion (13.5%). 17.1% had some infectious
      complications. Endometritis was the most frequent complicatrion (7.9%). Most of
      the infectious complications occurred in the clean cesarean sections (16.7%) and
      in the dirty cesarean sections (22.3%). The best use of antibiotics was observed
      in both groups (96.5 and 96.6%, respectively). Patients with an incorrect use of
      antibiotics had more infectious complications (37.8%). A statistical association
      was found between these 2 variables (p = 7.569 x 20).

PMID- 15844297
TI  - [Development of Tropical Medicine in Cuba: life and work of its highest
      exponent].
AB  - A brief historical review of Tropical Medicine in Cuba and of the life and work
      of Pedro Kouri up to the foundation of the institution that bears his name today
      was made. The achievements attained by this Institute were also included in this
      paper. With this study we payed a modest homage to the illustrous Dr. Pedro Kouri
      on the centenary of his birthday and the students and health workers had the
      opportunity to know part of this Cuban history.

PMID- 15844299
TI  - [Historical review about the research on toxoplasmosis].
AB  - Toxoplasmposis is one of the zoonotic diseases which is widely spread all over
      the world. It is caused by Toxoplasma gondii. In this paper we made a
      chronological synthesis of some of the numerous investigations that have been
      made in the world and in Cuba.

PMID- 15844300
TI  - [Contribution to knowledge about the permanence and circulation of poliovirus
      vaccine in the environment].
AB  - The erradication of poliomyelitis in the world is a goal that requires the
      adoption of effective and safe strategies for its attainment. Knowing how long
      the strains of poliovirus derived from the oral attenuated virus vaccine may
      circulate and remain in the environment was essential to define the measures to
      be taken and was also the objective of our paper. Specimens of stools and sewage
      water, which were weekly obtained at the end of the National Polio Vaccination
      Campaign, in 1998, were analyzed. Viruses were isolated and identified by culture
      and neutralization tests for the identification of poliovirus. In the particular
      case of the sewage water, it was also used the polymerase chain reaction. The
      curves of elimination in both media were drawn and it was concluded that the
      permanence of viruses in the environment did not exceed the 12 weeks after the
      immunization with the oral attenuated virus vaccine.

PMID- 15844301
TI  - Changes of single fiber electromyography in patients with inflammatory
      myopathies.
AB  - OBJECTIVE: To assess the significance of single fiber electromyography (SFEMG) in
      diagnosis of inflammatory myopathies and the correlation with other assistant
      examination findings. METHODS: SFEMG were recorded from the extensor digitorum
      communis of 34 patients with polymyositis or dermatomyositis and compared with
      the findings of routine electromyography (EMG), serum creatine kinase (CK)
      determination, and muscle biopsy. RESULTS: SFEMG recordings in 34 patients were
      all abnormal. The prominent feature was markedly increased fiber density (FD)
      with normally or mildly increased jitter. FD ranged from 1.0 to 6.0 (2.34 +/-
      0.43). Jitter ranged from 5 to 78 micros (41.6 +/- 10.3 micros). The potential
      pairs with jitter values greater than 55 micros ranged from 0% to 55% (7.7% +/-
      11.8%). Block was detected at one recording site in only one patient. Routine EMG
      demonstrated myogenic lesions in only 24 patients (70.6%). FD was a little higher
      in the normal-EMG subgroup or the neurogenic-EMG subgroup than myogenic-EMG
      subgroup but without statistical significance. Elevated CK levels were found in
      75% patients (24/32). FD in the normal CK subgroup was significantly higher than
      that in the elevated CK subgroup (2.62 +/- 0.40 vs. 2.28 +/- 0.40, P < 0.05).
      Muscle pathologies were consistent with the diagnosis of myositis in 75% (15/20).
      CONCLUSION: SFEMG is of great value in the diagnosis and disease process
      understanding of inflammatory myopathies for the clinically suspected patients
      with normal routine EMG, CK levels, and muscle biopsies.

PMID- 15844302
TI  - Prevention of pericardial constriction by transcatheter intrapericardial
      fibrinolysis with urokinase.
AB  - OBJECTIVE: To investigate whether intrapericardial urokinase irrigation along
      with pericardiocentesis could prevent pericardial constriction in patients with
      infectious exudative pericarditis. METHODS: A total of 94 patients diagnosed as
      infectious exudative pericarditis (34 patients with purulent pericarditis and 60
      with tuberculous pericarditis, the disease courses of all patients were less than
      1 month), 44 males and 50 females, aged from 9 to 66 years (mean 45.4 +/- 14.7
      years), were consecutively recruited from 1993 to 2002. All individuals were
      randomly given either intrapericardial urokinase along with conventional
      treatment in study group, or conventional treatment alone (including
      pericardiocentesis and drainage) in control group. The dosage of urokinase ranged
      from 200000 to 600000 U (mean 320000 +/- 70000 U). The immediate effects were
      detected by pericardiography with sterilized air and diatrizoate meglumine as
      contrast media. The long-term investigation depended on the telephonic survey and
      echocardiographic examination. The duration of following-up ranged from 8 to 120
      months (mean 56.8 +/- 29.0 months). RESULTS: Percutaneous intrapericardial
      urokinase irrigation promoted complete drainage of pericardial effusion,
      significantly reduced the thickness of pericardium (from 3.1 +/- 1.6 mm to 1.6 +/
      1.0 mm in study group, P < 0.001; from 3.4 +/- 1.6 mm to 3.2 +/- 1.8 mm in
      control group, P > 0.05, respectively), and alleviated the adhesion.
      Intrapericardial bleeding related to fibrinolysis was found in 6 of 47 patients
      with non-blood pericardial effusion and no systemic bleeding and severe puncture
      related complication was observed. In follow-up, there was no cardiac death, and
      pericardial constriction events were observed in 9 (19.1%) of study group and 27
      (57.4%) of control group. Cox analysis illustrated that urokinase could
      significantly reduce the occurrence of pericardial constriction (relative hazard
      coefficient = 0.185, P < 0.0001). CONCLUSION: The early employment of
      intrapericardial fibrinolysis with urokinase and pericardiocentesis appears to be
      safe and effective in preventing the development of pericardial constriction in
      patients with infectious exudative pericarditis.

PMID- 15844303
TI  - Intima-media thickness of carotid artery is associated with insulin sensitivity
      and glucose tolerance in elderly Chinese.

PMID- 15844304
TI  - Clinical advantages of total cavopulmonary anastomosis without cardiopulmonary
      bypass.
AB  - OBJECTIVE: To evaluate surgical methods and results of extracardiac conduit total
      cavopulmonary anastomosis (EC-TCPA) without cardiopulmonary bypass (CPB).
      METHODS: From May 2000 to April 2003, 11 patients with functional univentricle
      underwent off-pump EC-TCPA (no-CPB group). Their postoperative outcome was
      retrospectively compared with a 17-patient group who underwent EC-TCPA with
      cardiopulmonary bypass (CPB group) over a concurrent time period. RESULTS: There
      was 1 operative death in no-CPB group and 2 in CPB group; early postoperative
      hemodynamics appeared to significantly improve in no-CPB group. Blood and
      platelet transfusions decreased and blood plasma transfusion significantly
      lowered in no-CPB group compared with CPB group (P = 0.036). Postoperative
      courses of patients in no-CPB group were smooth and event free, and extubation
      time was substantially short Intensive cares unit stay (P = 0.04) and hospital
      stay (P = 0.02) postoperation were significantly shorter, hospital costs were
      significantly reduced (P = 0.004) in no-CPB group compared with CPB group.
      CONCLUSIONS: EC-TCPA without use of CPB is not a difficult procedure; the
      procedure results in improvement in postoperative hemodynamics, and decreased use
      of blood and blood products. It is a more efficient operation with more short
      recovery time and reduced hospital stay.

PMID- 15844305
TI  - Clinical observation of irbesartan in treatment of vasovagal syncope.

PMID- 15844306
TI  - Construction of hu-PBL/SCID chimeras and development of EBV-related lymphomas.
AB  - OBJECTIVE: To construct hu-PBL/SCID chimeras and to investigate the development
      of lymphoma and oncogenicity of the Epstein-Barr virus (EBV). METHODS: Human
      peripheral blood lymphocytes (PBLs) were isolated from healthy adult donors and
      transplanted intraperitoneally into severe combined immunodeficient (SCID) mice.
      Mice with hu-PBL engraftment from healthy EBV seronegative donors were injected
      intraperitoneally with EBV-containing supernatant from suspension culture of B95
      8 cell line (active infection), whereas mice receiving lymphocytes from healthy
      EBV seropositive donors were not re-infected with B95-8 derived EBV (latent
      infection). Pathological examination and molecular analysis were performed on
      experimental animals and induced neoplasms. RESULTS: In the early stage of this
      experiment, 12 mice died of acute graft-versus-host disease, mortality was 34.3%
      (12/35 mice) with an average life span of 17.5 days. In 19 survival hu-PBL/SCID
      chimeric recipients from 12 healthy donors, tumor incidence was 84.2% (16/19
      mice). The average survival time of tumor-bearing mice was 65.5 days. EBV-related
      neoplasms in SCID mice were nodular tumors with aggressive and fatal features.
      Histological morphology of tumors exhibited diffuse large cell lymphomas.
      Immunohistochemistry revealed that LCA (CD45) and L26 (CD20) were positive, but
      both PS1 (CD3) and UCHL-1 (CD45RO) were negative, and EBV products ZEBRA, LMP1,
      and EBNA2 were expressed in a small number of tumor cells. EB virus particles
      were seen in the nuclei of some tumor cells by electron microscopy, and EBV DNA
      could be amplified in the tumor tissues by PCR. In situ hybridization indicated
      that the nuclei of tumor cells contained human-specific Alu sequence.
      CONCLUSIONS: EBV-induced tumors were human B-cell malignant lymphomas. We
      obtained direct causative evidence dealing with EBV-associated tumor deriving
      from normal human cells.

PMID- 15844307
TI  - Effect of preoperative use of long-acting octreotide on growth hormone secreting
      pituitary adenoma and transsphenoidal surgery.
AB  - OBJECTIVE: To investigate whether somatostatin analog octreotide long acting
      release (LAR) shrinks growth hormone (GH) secreting adenomas, and improves the
      results of subsequent transsphenoidal surgery. METHODS: Seventeen previously
      untreated active acromegalic patients with pituitary adenomas were treated with
      LAR (30 mg intramuscular injection every 28 days) for 3 months prior to
      transsphenoidal surgery. Clinical reaction, mean GH secretion, and tumor volume
      were measured under basal conditions and after LAR treatment. RESULTS:
      Presurgical treatment improved acromegaly symptoms and induced a significant
      reduction of GH under the 5 ng/mL limit in microadenoma (P < 0.05), while only
      18.2% (2/11) in macroadenoma. Meanwhile, tumor shrinkage occurred in 58.8%
      (10/17) patients, with 1 case in the microadenoma group. All marked shrinkage (>
      25%) occurred in the macroadenoma group. Statistical analysis showed tumor
      shrinkage caused by LAR was greater in macroadenoma group than that in
      microadenoma group (P < 0.05). During operation, adenoma was soft in 15 cases,
      with the exception of 2 cases in which the soft tumor was divided by fibrous
      septa, but all tumor removal was smooth. CONCLUSIONS: A short term administration
      of preoperative LAR may induce a significant decrease in GH-secretion level and
      adenoma volume. Presurgical use of octreotide LAR improves surgical results
      especially in macroadenomas.

PMID- 15844308
TI  - Effects of SDS, PBS solutions upon fluorescence values of Dermatophagoides
      pterronyssinus radioallergosorbent test inhibition.
AB  - OBJECTIVE: To explore the effects of SDS, PBS re-dissolvent solutions on
      fluorescence values of radioallergosorbent test (RAST) inhibition. METHODS:
      Dermatophagoides pterronyssinus allergen immunoCAP and UniCAP 100 System were
      used. The Sera Pool consisted of 20 Dermatophagoides pterronyssinus allergic
      patients sera, their specific IgE fluorescence values were between 12505 and
      24776. RESULTS: Fluorescence value percentages decreased: 62.9%, 54.1%, 43.5%,
      6.7%, 3.7%, 2.6%, 2.2%, and 1.4% respectively, when SDS concentrations were at
      2%, 1%, 0.5%, 0.25%, 0.1%, 0.05%, 0.025%, and 0.01%. Fluorescence values
      decreased more than 5% with SDS concentrations equal to 0.25% or higher. PBS in
      0.1 and 0.01 mol/L concentrations decreased fluorescence values 2.9% and 0.9%
      respectively. CONCLUSIONS: SDS is a commonly used surfactants in allergen extract
      and re-dissolvent prepared allergen precipitation for RAST inhibition. Thus
      effects of surfactants (e.g. SDS) upon the RAST inhibition tests must be
      considered when they were used as re-dissolvent agents to improve protein
      resolution in RAST inhibition.

PMID- 15844309
TI  - A complete screen for mutations of the rhodopsin gene in a panel of Chinese
      patients with autosomal dominant retinitis pigmentosa.
AB  - OBJECTIVE: To evaluate the prevalence of rhodopsin (RHO) mutations and the
      genotype-phenotype relationships in Chinese patients with autosomal dominant
      retinitis pigmentosa (ADRP) by conformation sensitive gel electrophoresis (CSGE)
      and direct DNA sequencing. METHODS: We have screened the five coding exons and
      splice sites of RHO gene in 27 probands who had no relativity from Chinese ADRP
      families and 100 normal controls to identify disease-associated mutations, using
      CSGE and direct DNA sequencing. Family members of some probands with disease
      associated mutations were also genotyped to determine whether the RHO mutations
      segregated with retinitis pigmentosa (RP) in their families. RESULTS: Two RHO
      mutations, Pro347Leu and Pro327 (1-bp del), were identified separately in two
      families, thus the frequency of RHO mutations among this set of Chinese ADRP
      families is about 7.4% (2/27). Pro347Leu mutation was found in one ADRP proband
      as well as three her children who also had RP. She had relatively early onset at
      about 17 years. The only one child without this mutation had no symptom or sign
      of RP at age of 34. Pro327 (1-bp del) was identified in a late-onset ADRP
      patient, who appeared night blindness around 30 years old and in her fifties
      electroretinogram (ERG) has been flat in both scotopic and photopic phases.
      Family analysis showed that this mutation also existed in her younger daughter
      and her elder sister, both of them also had RP. Three other family members were
      genotypically and phenotypically normal. Neither of the two mutations was
      detected in 100 normal controls. CONCLUSIONS: The frequency of RHO mutations in
      Chinese patients was lower than that in Europe and North America. The phenotype
      of the patients with Pro347Leu corresponded to type 1 ADRP, with severe rod
      degeneration and some cone preservation later, while the phenotype of the
      patients carrying Pro327 (1-bp del) corresponded to type 2 ADRP, with a
      concomitant loss of rod and cone visual function. CSGE was found to be a
      sensitive, simple, and practical method for the screening of a large number of
      samples under highly reproducible conditions, and could be utilized in routine
      molecular diagnostic laboratories.

PMID- 15844310
TI  - Analysis of risk factors in 3901 patients with stroke.
AB  - OBJECTIVE: To estimate the frequency of various risk factors for overall stroke
      and to identify risk factors for cerebral infarction (CI) versus intracerebral
      hemorrhage (ICH) in a large hospital-based stroke registry. METHOD: Data from a
      total of 3901 patients, consisting of 3525 patients with CI and 376 patients with
      ICH were prospectively coded and entered into a computerized data bank. RESULTS:
      Hypertension and smoking were the most prominent factors affecting overall stroke
      followed by mild internal carotid artery stenosis (< 50%), hypercholesterolemia,
      transient ischemic attacks (TIAs), diabetes mellitus, and cardiac ischemia.
      Univariate analysis showed that factors in male significantly associated with CI
      versus ICH were old age, a family history of stroke, and intermittent
      claudication; whereas in female the factors were oral contraception and migraine.
      By multivariate analysis, in all patients, the factors significantly associated
      with CI as opposed to ICH were smoking, hypercholesterolemia, migraine, TIAs,
      atrial fibrillation, structural heart disease, and arterial disease. Hypertension
      was the only significant factor related with ICH versus CI. CONCLUSIONS: The
      factors for ischemic and hemorrhagic stroke are not exactly the same. Cardiac and
      arterial disease are the most powerful factors associated with CI rather than
      ICH.

PMID- 15844311
TI  - Laparoscopic surgery in patients with hypovolemic shock due to ectopic pregnancy.
AB  - OBJECTIVE: To evaluate the feasibility and safety of operative laparoscopy for
      ectopic pregnancy with hypovolemic shock. METHODS: Two hundred and fifteen women
      with ectopic pregnancy underwent operative laparoscopy. These patients were
      divided into two groups. The study group included 21 patients with shock and
      intraperitoneal hemorrhage more than 1000 mL, and control group included 194
      patients, hemodynamically stable, with blood loss less than 1000 mL. Clinical
      data of perioperative periods in two groups were retrospectively analyzed.
      RESULTS: All patients were tubal pregnancies. The occurrence rate of tubal
      rupture was higher in study group than in control group (80.95% vs. 15.98%, P <
      0.001). Intraabdominal blood loss was significantly higher in study group than in
      control group (1900 mL vs. 300 mL, P < 0.001), and autologous blood transfusions
      were given to 95.24% and 9.3% of patients in study and control group,
      respectively (P < 0.001). Laparoscopic salpingectomy was performed on 85.7 % and
      50.5% of patients in study and control group (P < 0.001). The operative time was
      somewhat longer in study group than that in control group (60 minutes vs. 45
      minutes), but with no significant difference. All patients had no perioperative
      complications. CONCLUSION: Operative laparoscopy in patients with hopovolemic
      shock can be safely and effectively performed by experienced laparoscopists with
      the aid of optimal anesthesia, advanced cardiovascular monitoring, and autologous
      blood transfusion.

PMID- 15844312
TI  - Clinical application of botulinum toxin type B in movement disorders and
      autonomic symptoms.
AB  - OBJECTIVE: [corrected] To evaluate efficacy and safety of botulinum toxin type B
      (BTX-B) in treatment of movement disorders including blepharospasm, oromandibular
      dystonia, hemifacial spasm, tremor, tics, and hypersecretory disorders such as
      sialorrhea and hyperhidrosis. METHODS: A retrospective study of BTX-B injections
      in treatment of 58 patients with various neurological disorders was performed.
      The mean follow-up time was 0.9 +/- 0.8 years. Results of the first and last
      treatment of patients with at least 3 injection sessions were compared. RESULTS:
      The response of 58 patients to a total of 157 BTX-B treatment sessions was
      analyzed. Of the 157 treatment sessions, 120 sessions (76.4%) resulted in
      moderate or marked improvement while 17 sessions (10.8%) had no response. The
      clinical benefits after BTX-B treatment lasted an average of 14 weeks. Of the 41
      patients with at least 3 injection sessions (mean 10 +/- 8.6), most patients
      needed increased dosage upon the last session compared to the first session.
      Nineteen patients (32.8%) with 27 sessions (17.2%) reported adverse effects with
      BTX-B treatment. CONCLUSIONS: Though most patients require increased dosage to
      maintain effective response after repeated injections, BTX-B is an effective and
      safe treatment drug for a variety of movement disorders, as well as drooling and
      hyperhidrosis.

PMID- 15844313
TI  - Improving P-gp expression in human mononuclear cells in vitro transfected by
      multidrug resistance-1 mRNA.
AB  - OBJECTIVE: To evaluate the expression and function activity of P-glycoprotein (P
      gp) in human mononuclear cells (MNCs) in vitro transfected by multidrug
      resistance-1 (MDR1) mRNA. METHODS: Two MDR1 cDNA vectors, pT7TS_MDR1 and
      pGEM5Zf(+)_MDR1, were constructed and transcripted in vitro. Vector
      pGEM5Zf(+)_MDR1 only contained the coding region of mdr1 cDNA, and pT7TS_MDR1
      also included Xeponus beta-globin 5' and 3' untranslated region. MNCs were
      prepared from peripheral blood of parvicellular lung cancer patient. The two
      human mdrl mRNAs were then transferred into human MNCs in vitro by DOTAP. And the
      expression efficiency and pump function of P-gp were measured with flow
      cytometry. RESULTS: Expression of P-gp significantly elevated in both transferred
      cells compared with untransferred cells (P < 0.01). And pT7TS_MDR1 showed higher
      capability in elevating the expression of P-gp than pGEM5Zf(+)_MDR1 (P < 0.01).
      The P-gp function was elevated in both pT7TS_MDR1 and pGEM5Zf(+) MDR1 groups. The
      survival ratio of MNCs in erythrocyte-lysis-solution (ELS, 86.07%) and lymphocyte
      isolation-solution (LIS, 83.67%) had no significant difference. The CD34+ cells
      content of the MNCs used for transfection was 2.65% and 1.01% in ELS and LIS
      group, respectively (P < 0.01). CONCLUSIONS: It is a feasible approach to improve
      P-gp expression in human MNCs by transfection of MDR-1 mRNA. And the ELS may be
      more suitable for purifing MNCs for mRNA transfection than LIS.

PMID- 15844314
TI  - Effects of retinoic acid on proliferation and differentiation of a human ovarian
      carcinoma cell line: 3AO.
AB  - OBJECTIVE: To observe the effects of retinoic acid (RA) on the proliferation and
      differentiation of a human ovarian carcinoma cell line: 3AO cells. METHODS: 3AO
      cell proliferation was evaluated by viable cell count, percentage of cells in
      each cycle phase were analyzed by flow cytometric analysis, alkaline phosphatase
      (AKP) activity was determined as described, and CA125 expression was measured by
      ELISA. RESULTS: RA could inhibit the proliferation of 3AO cells accompanied with
      morphological changes in a dose-dependent manner. Cell cycle analysis indicated
      that RA inhibition of 3AO cells growth occurred through induction of G1 arrest
      with a concomitant reduction in the proportion of cells in S phase, AKP activity
      increased significantly after treatment with RA (0.1 micromol/L) for 1-5 days.
      Dose-response studies revealed that the AKP activity increased to a different
      extent as a function of RA concentrations. Furthermore, RA could suppress the
      expression of CA125 tumor marker in 3AO cells. CONCLUSION: RA could markedly
      inhibit the proliferation and induce the differentiation of 3AO cells.

PMID- 15844315
TI  - Clinical analysis of Turner's syndrome.

PMID- 15844316
TI  - Effects of acute hypoglycemia on the orexin system in rat.
AB  - OBJECTIVE: To evaluate the effects of acute glucose level changes on expression
      of prepro-orexin, orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) mRNA in
      rat hypothalamus tissue and pancreatic islets cells. METHODS: Thirty adult male
      Wistar rats were randomly divided into three equal groups (n = 10). The acute
      hypoglycemia rat model was induced by a single subcutaneous injection of insulin.
      Twenty acute hypoglycemia rats were divided into group B and group C. Group B was
      allowed to eat freely, while group C was food-deprived. Control rats were
      injected the same volume of saline. The effect of glucose levels (2.8 mmol/L and
      8.3 mmol/L) on pancreatic islet cell orexin system was detected in pancreas islet
      cell cultured in vitro. The expression of prepro-orexin and OXR mRNA was examined
      in rat hypothalamus tissue and pancreatic islets cell cultured in vitro using
      reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Expression of
      orexin mRNA increased about 150% for the food-deprived hypoglycemia rats in
      comparison with control group (P < 0.01), whereas expression of OX1R mRNA
      decreased up to 30% (P < 0.01). However, expression of OX2R mRNA was unchanged in
      comparison with control group. In vitro, after incubation with 2.8 mmol/L glucose
      for 6 hours, the expression of prepro-orexin mRNA increased 2 times in rat
      pancreas islet cells in comparison with 8.3 mmol/L glucose group (P < 0.01). But
      the expression of OX1R mRNA was not sensitive to acute glucose fluctuation.
      CONCLUSIONS: Orexin in rat hypothalamus is stimulated by decline in blood glucose
      and inhibited by signals related to feeding. Moreover, glucose plays a role in
      modulating the gene expression of prepro-orexin in rat pancreatic islet cells.

PMID- 15844317
TI  - Application of lornoxicam to patient-controlled analgesia in patients undergoing
      abdominal surgeries.
AB  - OBJECTIVE: To assess the efficacy and safety of lornoxicam, one non-steroidal
      anti-inflammatory drug (NSAID) in patient-controlled analgesia (PCA) in patients
      undergoing abdominal surgeries. METHODS: Thirty-nine patients scheduled for
      abdominal surgeries were randomly assigned to different PCA treatment groups
      using either lornoxicam or fentanyl postoperatively. Pain intensity difference
      (PID) and sum of pain intensity difference (SPID) were used to assess the
      analgesic efficacy of both drugs during a 24-hour period. RESULTS: The analgesic
      efficacy of lornoxicam is 1/66 of fentanyl, which was shown by SPID value of
      3.250 and 3.058, respectively (P > 0.05). Lornoxicam caused fewer adverse events
      than fentanyl (33% vs. 68%, P < 0.05). CONCLUSION: In clinic, we can use
      lornoxicam to treat postoperative pain effectively and with less adverse
      reactions compared with fentanyl.

PMID- 15844318
TI  - Relationship between endothelial dysfunction and serum homocysteine in patients
      with coronary lesions.
AB  - OBJECTIVE: To investigate the relationship between vascular endothelial
      dysfunction and serum homocysteine (HCY) level in patients with coronary lesions.
      METHODS: Serum HCY, serum nitric oxide (NO), plasma endothelin-1 (ET-1), and
      circulation endothelial cell (CEC) were measured in 76 patients who received
      coronary angiography. Fifty-four patients with a stenosis of 50% or more at least
      in one coronary atery were as coronary artery disease (CAD) group. Other 22 cases
      with no recognizable plaque and/or stenosis were as control group. HCY level was
      detected using an enzyme immunoassay kit. NO concentration was measured using a
      nitrate reductase kit. Radio-immunoassay was applied to analyse the ET-1 level,
      and CEC was measured by flow cytometry. RESULTS: The levels of HCY, ET-1, and CEC
      in patients with coronary lesions were significantly increased in comparison with
      control group (P < 0.01), while NO level in CAD group was significantly lower
      compared with that in control (P < 0.01). Using a multivariate stepwise
      regression analysis, HCY level had a positive correlation with ET-1 level (r =
      0.420, P < 0.05) and CECs number (r = 0.423, P < 0.05); and had a negative
      correlation with NO/ET-1 (r = -0.403, P < 0.05). But there was no significant
      correlation between HCY and NO levels. CONCLUSIONS: HCY might lead to endothelial
      cell injury, which would provide a plausible mechanism for the relationship
      between hyperhomocysteinemia and development of coronary artery disease. HCY can
      be considered as a predictor for preliminary or active coronary lesion.

PMID- 15844319
TI  - Effects of prostaglandin E1 on the progression of aristolochic acid nephropathy.
AB  - OBJECTIVE: To investigate the effects of prostaglandin E1 (PGE1) on the
      progression of aristolochic acid nephropathy (AAN). METHODS: Twenty-four patients
      diagnosed as AAN with serum creatinine (Scr) between 1.5 mg/dL and 4 mg/dL during
      September 2001 to August 2003 were randomly divided into 2 groups. All patients
      had ingested long dan xie gan wan containing aristolochic acid (0.219 mg/g) for
      at least 3 months. Twelve patients were injected with Alprostadil (10 microg/d
      for 10 days in one month, summing up to 6 months). Except for PGE1, the other
      therapy was same in both groups. Renal function was assessed using reciprocal
      serum creatinine levels (1/Scr). RESULTS: The level of Scr an d serum hemoglobin
      (Hgb) was similar in both groups prior to therapy. During follow-up, 1/Scr levels
      in PGE1 group were significantly higher than control group (P < 0.01), and Hgb
      levels in PGE1 group were significantly increased compared with control (P <
      0.05). CONCLUSION: PGE1 can slow the progression of renal failure and increase
      Hgb level of AAN patient.

PMID- 15844320
TI  - Clinical effects of ropivacaine mesylate in epidural anesthesia and analgesia.

PMID- 15844321
TI  - Obstruction of right ventricular outflow tract caused by intracavitary metastatic
      disease of pancreatic tumor.

PMID- 15844322
TI  - Surface modification of microchip input reservoirs for pressure-induced sample
      injection into microreactors.
AB  - Optimization of geometry and surface modification of microchip input reservoirs
      were performed to achieve uninterferenced pressure-induced sample injection of
      multiple samples into microreactors using a single syringe pump. Nine samples of
      3.5 microL were pipetted onto input reservoirs and loading of PCR mixture into
      260 nL microreactors was achieved followed by successful PCR amplification,
      confirming that no cross-contamination occurs during injection.

PMID- 15844323
TI  - Toward selectivity control of a heme peptide electrode by modification with a
      phase-transition polymer.
AB  - Reduction currents for H2O2 at a heme peptide (HP)-modified electrodes are
      suppressed by inhibitors, such as imidazole derivatives. Although this inhibition
      effect allows determinations of the total inhibition ability of imidazole
      derivatives, it has no selectivity. In this study the selectivity control of HP
      modified electrodes for imidazole derivatives was performed utilizing the
      thermoresponsive phase transition of poly(N-isopropylacrylamide), which was
      chemically immobilized on HP-modified electrodes. The inhibition ratios for
      imidazole derivatives appeared to be small at temperatures below the lower
      critical solution temperature (LCST), and to be large above the LCST. This change
      was ascribed to a steric hindrance caused by a phase transition of the polymer.
      On the other hand, the inhibition ratio for histamine, which has a larger
      molecular size relative to imidazole, was not significantly changed by the phase
      transition. Thus, the selectivity of the HP-modified electrode was found to be
      controllable using an immobilized phase-transition polymer.

PMID- 15844324
TI  - Escherichia coli O157:H7 detection limit of millimeter-sized PZT cantilever
      sensors is 700 cells/mL.
AB  - A composite self-excited millimeter-sized lead zirconate titanate (PZT) glass
      cantilever (2 mm x 1.8 mm; sensing area of 6 mm2) was fabricated for the
      detection of Escherichia coli (E. coli) O157:H7. The fundamental and second mode
      resonance in air was 10.95 +/- 0.05 kHz and 43.45 +/- 0.05 kHz, respectively.
      Affinity purified monoclonal antibody (anti-E. coli O157:H7) specific to the
      pathogen E. coli O157:H7 was immobilized at the cantilever glass tip, and then
      immersed in liquid containing the pathogen (70 to 7 x 10(7) cells/mL). The
      resonant frequency showed a reduction and reached a steady state shift of 0 +/-
      5, 46 +/- 5, 260 +/- 5, and 1010 +/- 5 Hz corresponding to 0, 700, 7000, and 7 x
      10(7) cells/mL. From the experiments conducted, the detection limit of the sensor
      was 700 cells/mL.

PMID- 15844325
TI  - Discrimination of D-enantiomers of amino acids from L-ones through an inorganic
      reaction.
AB  - This paper reports on an inorganic reaction that performs complete discrimination
      of D- and L-enantiomers from each other in an aqueous solution at room
      temperature. This is the first finding of an inorganic reaction that acts like an
      organic biosystem in the sense that such a kind of complete discrimination of
      enantiomers is a matter solely done through biosystems in nature. We also assume
      that they suggest significant concerns with not only analytical chemistry in
      regards to the discrimination of isomers, but also with cosmo/geo-chemistry.

PMID- 15844326
TI  - Recognition of bile acids at cyclodextrin-modified gold electrodes.
AB  - Lipoylamino-beta- and gamma-cyclodextrin (LP-beta-CD and LP-gamma-CD,
      respectively) were adsorbed at the surface of gold electrodes by sulfur-gold
      bonding. The resultant electrodes exhibited quasi-reversible voltammograms for
      the redox reaction of Fe(CN)6(3-/4-) in aqueous solutions, with peak-to-peak
      separation (deltaEp) being 85 mV at 20 mV s(-1) as a potential sweep rate. When
      bile acids are added to the solution, deltaEp values increased to 200-300 mV with
      increasing the concentration of bile acids. A Langmuir-type adsorption analyses
      satisfactorily afforded the binding constants (Ksurf) of the surface-confined LP
      beta-CD and LP-gamma-CD with the bile acids. The obtained Ksurf values of LP
      gamma-CD are 5.0-50 times larger than the corresponding binding constants of
      gamma-CD in homogeneous aqueous solutions. Cyclic voltammetric experiments with
      positively, negatively, and non-charged adamantane derivatives as well as pH
      titration experiments revealed that the retardation of the electrode reaction of
      negatively charged Fe(CN)6(3-/4-) caused by bile acids was attributable (1) to
      electric potential changes due to the accumulation of the negative charges at the
      electrode surface, and (2) to an increase in the hydrophobicity of the electrode
      surface due to the binding of hydrophobic bile acids to the LP-beta-CD and LP
      gamma-CD membranes.

PMID- 15844327
TI  - An amperometric glucose biosensor based on glucose oxidase immobilized in
      electropolymerized poly(o-aminophenol) and carbon nanotubes composite film on a
      gold electrode.
AB  - An amperometric glucose biosensor is developed that is based on immobilization of
      glucose oxidase (GOD) in a composite film of poly(o-aminophenol) (POAP) and
      carbon nanotubes (CNT), which are electrochemically co-polymerized at a gold (Au)
      electrode. Because of the high surface per volume ratio and excellent electrical
      conductivity of CNT, the biosensor based on an Au/POAP/CNT/GOD electrode has
      lower detection limit (0.01 mM), larger maximum response current (0.24 mA cm(-2))
      and higher sensitivity (11.4 mA M(-1) cm(-2)) than the values of the biosensor
      based on an Au/POAP/GOD electrode. Additionally, the biosensor shows fast
      response time, large response current, and good anti-interferent ability for
      ascorbic acid, uric acid and acetaminophen. Good reproducibility and stability of
      the biosensor are also observed.

PMID- 15844328
TI  - Terbium sensitized determination of tosufloxacin using electrochemiluminescence
      method.
AB  - A novel method for determination of trace amounts of tosufloxacin (TFLX) based on
      electrochemiluminescence (ECL) has been developed. The calibration graphs for
      TFLX were linear in the range of 5.0 x 10(-11)-3.5 x 10(-7) mol/L, with the
      detection limit of 1.3 x 10(-11) mol/L. Key factors affecting the determination
      of TFLX were investigated. TFLX amounts in capsule and serum samples were
      successfully detected by this method. A possible mechanism of energy transfer,
      and thus the explanation of ECL in the Tb3+-TFLX-Na2S2O4 system are discussed.

PMID- 15844329
TI  - Electrocatalytic oxidation of hydrogen peroxide and cysteine at a glassy carbon
      electrode modified with platinum nanoparticle-deposited carbon nanotubes.
AB  - A glassy carbon electrode modified with platinum nanoparticle-decorated carbon
      nanotubes (Pt-CNT/GCE) was prepared. The electrochemical behaviors for the
      catalysis oxidations of hydrogen peroxide and cysteine were studied. The Pt
      CNT/GCE showed catalytic activity for electro-oxidation of hydrogen peroxide at
      0.6 V in PBS (pH = 7.0) and for that of cysteine at 0.55 V in sulfuric acid
      medium (pH <or = 2). The results indicated that the peak currents were
      proportional to the concentrations of both hydrogen peroxide and cysteine; the
      currents at Pt-CNT/GCE were almost 3-times higher than that at Pt electrode. The
      electrocatalytic oxidation mechanisms for hydrogen peroxide and cysteine at Pt
      CNT/GCE surface were briefly studied.

PMID- 15844330
TI  - Natural analcime zeolite modified with 5-Br-PADAP for the preconcentration and
      anodic stripping voltammetric determination of trace amount of cadmium.
AB  - A procedure for separation and preconcentration of trace amounts of cadmium has
      been proposed. A column of analcime zeolite modified with
      benzyldimethyltetradecylammonium chloride and loaded with 2-(5-bromo-2
      pyridylazo)-5-diethylaminophenol (5-Br-PADAP) was used for retention of cadmium.
      The cadmium was quantitatively retained on the column at pH approximately 9 and
      was recovered from column with 5 ml of 2 M nitric acid with a preconcentration
      factor of 140. Anodic stripping differential pulse voltammetry was used for
      determination of cadmium. A 0.05 ng/ml detection limit for the preconcentration
      of aqueous solution of cadmium was obtained. The relative standard deviation
      (RSD) for eight replicate determinations at the 1 microg/ml cadmium levels was
      0.31% (calculated with the peak height obtained). The calibration graph using the
      preconcentration system was linear from 0.01 to 150 microg/ml in final solution
      with a correlation coefficient of 0.9997. For optimization of conditions, various
      parameters such as the effect of pH, flow rate, instrumental conditions and
      interference of number of ions, were studied in detail. This method was
      successfully applied for determination of cadmium in various complex samples.

PMID- 15844331
TI  - Determination of silver(I) by electrothermal-AAS in a microdroplet formed from a
      homogeneous liquid-liquid extraction system using
      tetraspirocyclohexylcalix[4]pyrroles.
AB  - A simple and efficient method for the selective separation and preconcentration
      of Ag+ using homogeneous liquid-liquid extraction was developed.
      Tetraspirocyclohexylcalix[4]pyrrole (TSCC4P) was synthesized and investigated as
      a suitable selective complexing ligand for Ag+. Zonyl FSA (FSA) was applied as a
      phase-separator agent under mild pH conditions. Under the optimal conditions
      ([TSCC4P] = 3.4 x 10(-4) M, [THF] = 25.0% v/v, [FSA] = 1.25% w/v, and pH = 4.5),
      5 microg of Ag+ in 6.0 ml aqueous phase could be extracted quantitatively into 20
      microl of the sedimented phase. The maximum concentration factor was 300-fold.
      The limit of detection of the proposed method was 0.005 ng/ml. The
      reproducibility of the proposed method was at most 3.5%. The influence of the pH,
      type and volume of the water-miscible organic solvent, concentration of FSA,
      concentration of the complexing ligand and the effect of different diverse ions
      on the extraction and determination of Ag+ were investigated. The proposed method
      was applied to the extraction and determination of Ag+ in different water
      samples.

PMID- 15844332
TI  - Retentivity and enantioselectivity of uniformly-sized molecularly imprinted
      polymers for (S)-nilvadipine in aqueous and non-aqueous mobile phases.
AB  - Uniformly-sized molecularly imprinted polymers (MIPs) for (S)-nilvadipine have
      been prepared by a multi-step swelling and polymerization method using
      methacrylic acid or 4-vinylpyridine (4-VPY) as a functional monomer, ethylene
      glycol dimethacrylate (EDMA) as a cross-linker, and toluene, chloroform,
      cyclohexanol or phenylacetonitrile as a porogen. The chiral recognition abilities
      of the MIPs for nilvadipine were evaluated using aqueous and non-aqueous mobile
      phases. Among the MIPs, the (S)-nilvadipine-imprinted 4-VPY-co-EDMA polymers
      prepared using toluene as a porogen showed the highest recognition ability for
      nilvadipine in both aqueous and non-aqueous mobile phases. In addition to
      molecular shape recognition, hydrogen-bonding interactions of the NH proton of
      nilvadipine with a pyridyl group of the (S)-nilvadipine-imprinted 4-VPY-co-EDMA
      polymers could play an important role in the retention and chiral recognition of
      nilvadipine in aqueous and non-aqueous mobile phases. Furthermore, the MIP for
      (S)-nilvadipine gave the highest molecular recognition ability when a porogenic
      solvent during polymerization was used as the mobile phase modifier.

PMID- 15844333
TI  - Molecular-dynamics simulation for the characterization of liquid chromatographic
      stationary phase: effect of temperature.
AB  - The influence of temperature on the surface structure of the octadecylsilica
      (ODS) bonded phase was investigated with a molecular dynamics (MD) simulation.
      The MD simulation was applied to a molecular model consisting of three parts:
      amorphous silica base, dimethyloctadecylsilyl ligands and n-hexane as a mobile
      phase solvent. More detailed information on the effect of temperature was
      obtained at the low temperature region than that reported in our previous study.
      The motion of ODS ligands could be estimated by the mean square displacement
      (MSD) of the terminal carbon atoms of ODS ligands. The gauche fraction in the ODS
      ligand conformation can also be estimated to obtain the ligand conformation for
      each simulation condition in detail. It can be seen that an elevated temperature
      induced the more bent ligand conformation. The trend has a good agreement to that
      of the results experimentally observed by using various spectroscopic techniques
      such as nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy
      (FT-IR), and Raman spectroscopy.

PMID- 15844334
TI  - Photocontrollable cation extraction with crowned oligo(spirobenzopyran)s.
AB  - The photoinduced changes of metal-ion extractability of crown ether derivatives
      bearing three or four spirobenzopyran moieties and their analogues were studied
      using 1,2-dichloroethane as the organic solvent. Under dark conditions, these
      compounds extracted Cu2+, Ag+, and Pb2+ with their counteranions from the aqueous
      phase to the organic phase. The extraction equilibrium constants of the
      photochromic crown ether derivatives for Cu2+ and Ag+ were determined
      successfully. Under UV-light irradiation conditions, the extraction of Cu2+ by
      crowned tris(spirobenzopyran) was enhanced, while that of Ag+ was suppressed.
      During the competitive metal-ion extraction of crowned oligo(spirobenzopyran)s
      between Cu2+ and Ag+, the metal-ion selectivity was reversed explicitly by
      photoirradiation.

PMID- 15844335
TI  - Fluorometric method for quantitative determination of glucose and its application
      to human serum.
AB  - By coupling the Fenton reaction with the glucose oxidase (GOD)-catalyzed
      reaction, we have developed a fluorometric method for the determination of
      glucose; the linear response range and the detection limit are 0.108-2.59
      microg/ml and 0.0432 microg/ml, respectively. This approach is selective and has
      the advantages of using inexpensive reagents and avoiding interferences.
      Satisfactory results were obtained for the determination of glucose in human
      serum samples.

PMID- 15844336
TI  - Droplet-based micro-flow chemiluminescence system for in vivo glucose
      determination by microdialysis sampling.
AB  - A micro-flow chemiluminescence (CL) system in vivo for glucose determination by
      the on-line microdialysis sampling is described in this paper. The micro-flow CL
      system uses discrete sample droplets, which formed at the tip of the capillary
      with the sampling volume of 4.5 microl. The sol-gel method is introduced to co
      immobilize horseradish peroxidase (HRP) and glucose oxidase (GOD) on the inside
      surface of the micro-flow cell which was fabricated in polymethyl methacrylate
      (PMMA). The CL detection involved enzymatic oxidation of glucose to D-gluconic
      acid and H2O2, then H2O2 oxidizing luminol to produce CL in presence of HRP. The
      microdialysis probe was utilized for sampling in the rabbit blood; the sample
      throughput was 20 h(-1). The glucose level in blood of the rabbit was on-line
      monitored with good results.

PMID- 15844337
TI  - Switching of PET fluorescence signals induced by ligand exchange reactions of N
      (9-anthrylmethyl)amine on Cu(II) complexes and its application to postcolumn
      detection of glyphosate.
AB  - N-(9-Anthrylmethyl)amines which combine a fluorescent subunit and a chelate
      forming fragment have revealed a signal switching property in an aqueous solution
      upon complexation (off) with Cu(II) and liberation (on) of the probe molecule by
      substitution with an other ligand. The ligand exchange reaction between N
      (phosphonomethyl)glycine (glyphosate), a typical herbicide, with N-(9
      anthrylmethyl)amines on Cu(II) ion leads the fluorescence signal intensity to
      revive, providing an indirect detection system of glyphosate available in water
      of neutral pH region. The present system has been applied to the post column
      detection in the ion chromatographic separation of glyphosate and its metabolite
      aminomethylphosphonic acid (AMPA).

PMID- 15844338
TI  - Determination of trace water in gas samples by an improved Karl Fischer
      coulometer.
AB  - The determination of trace water in gas samples, such as isobutene, chloromethane
      (polymeric staple gases) and SF6 by a conventional Karl Fischer coulometer is
      very difficult, because of the adsorption of trace water on the surface of sample
      pipe, the gasification of the liquefied samples, and the migration of moisture
      into the measuring cell from the surroundings. To solve these problems, we
      improved a device for coulometric determination of water by Karl Fischer method.
      The improved coulometer was used to determine the trace water in isobutene,
      chloromethane and SF6; RSD was less than 5%, and recoveries ranged from 94.1 to
      109.1%, which is adequate for the analysis of industry.

PMID- 15844339
TI  - Precise Zn isotopic ratio measurements of human red blood cell and hair samples
      by multiple collector-ICP-mass spectrometry.
AB  - Precise 66Zn/64Zn and 68Zn/64Zn isotopic ratios of biochemical samples have been
      measured using multiple collector-ICP-mass spectrometry (MC-ICPMS). In order to
      eliminate the mass spectrometric interferences on Zn isotopes (e.g., 64Ni+ and
      136Ba2+), we chemically purified the analyte using an ion chromatographic
      technique. The resulting precisions of the 66Zn/64Zn and 68Zn/64Zn ratio
      measurements were 0.05/1000 and 0.10/1000 (2SD), respectively, which were enough
      to detect the isotopic variation of Zn in nature. Red blood cell (RBC) samples
      were collected from five volunteers (four males and one female), including a
      series of 12 RBC samples from one person through monthly-based sampling over a
      year. These were analyzed to test possible seasonal changes and variations in
      66Zn/64Zn and 68Zn/64Zn ratios among the individuals. The 66Zn/64Zn and 68Zn/64Zn
      ratios for a series of 12 RBC samples collected over a year were 0.43/1000 and
      0.83/1000 higher than the values of highly purified Zn metal (JMC Zn), and no
      seasonal change could be found. The 66Zn/64Zn and 68Zn/64Zn ratios for RBC
      samples collected from five volunteers did not vary significantly. In order to
      investigate Zn isotopic heterogeneity in a human body, Zn isotopic ratios of a
      hair sample collected from one of the volunteers was also analyzed. The 66Zn/64Zn
      and 68Zn/64Zn ratios for the hair sample were 0.59/1000 and 1.14/1000 lower than
      the mean value of RBC samples. This result demonstrates that detectable isotopic
      fractionation occurs in the human body. The data obtained here suggest that the
      isotopic ratios of trace metals could provide new information about
      transportation of metal elements in vivo.

PMID- 15844340
TI  - Electrooxidation of vanillyl alcohol in acidic aqueous solution using rotating
      ring-disk electrode voltammetry.
AB  - The electrooxidation of benzylic alcohol derivative in acidic aqueous solution
      shows an oxidation pre-peak in the cyclic voltammogram, which means that the
      reaction is proceeding via an ECE mechanism where the second electron transfer
      occurs at a less positive potential. From the result of the rotating ring-disk
      electrode voltammetry, the initial oxidation response of the electrode reaction
      can be extracted.

PMID- 15844341
TI  - Separation and enrichment of arsenic(V) with composite resin beads containing
      magnetite crystals.
AB  - The adsorption of arsenic(V) was investigated using macroporous resin beads
      containing magnetite crystals. Arsenic(V) was favorably adsorbed at pH 2-9, where
      the distribution coefficients were larger than 10(3). The maximum capacity was
      0.050 mmol/g. Metal cations including Ca(II), Mn(II), Co(II), Ni(II), Cu(II),
      Zn(II) and La(III) did not give serious interference at 10(-4) M level. Diluted
      arsenic(V) was collected with a packed column, and the retained arsenic(V) was
      quantitatively eluted out with 1 M NaOH.

PMID- 15844342
TI  - Simple bead injection-flow injection system for the determination of copper.
AB  - We demonstrate the extended application of a simple bead injection-flow injection
      system with a modified simple colorimetric detection unit for the determination
      of low amount of Cu2+ in samples of different matrices (water and supplement
      tablet samples) with minimal sample pretreatment by employing ammonium
      pyrrolidinedithiocarbamate (APDC) reagent.

PMID- 15844343
TI  - Determination of acetaldehyde in fuel ethanol by high-performance liquid
      chromatography with electrochemical detection.
AB  - The cyclic voltammetric behavior of acetaldehyde and the derivatized product with
      2,4-dinitrophenylhydrazine (DNPHi) has been studied at a glassy carbon electrode.
      This study was used to optimize the best experimental conditions for its
      determination by high-performance liquid chromatographic (HPLC) separation
      coupled with electrochemical detection. The acetaldehyde-2,4
      dinitrophenylhydrazone (ADNPH) was eluted and separated by a reversed-phase
      column, C18, under isocratic conditions with the mobile phase containing a binary
      mixture of methanol/LiCl(aq) at a concentration of 1.0 x 10(-3) M (80:20 v/v) and
      a flow rate of 1.0 mL min(-1). The optimum condition for the electrochemical
      detection of ADNPH was +1.0 V vs. Ag/AgCl as a reference electrode. The proposed
      method was simple, rapid (analysis time 7 min) and sensitive (detection limit
      3.80 microg L(-1)) at a signal-to-noise ratio of 3:1. It was also highly
      selective and reproducible [standard deviation 8.2% +/- 0.36 (n = 5)]. The
      analytical curve of ADNPH was linear over the range of 3-300 mg L(-1) per
      injection (20 microL), and the analytical recovery was > 99%.

PMID- 15844344
TI  - Fluorimetric determination of peroxynitrite based on an enzymatic reaction.
AB  - A novel fluorimetric method for the determination of peroxynitrite (ONOO-) using
      hemoglobin (Hb) as a catalyst is described. The method employs the reaction of
      ONOO with thiamine (TM), a colorless, non-fluorescent reagent in a glycine-NaCl
      NaOH buffer solution (pH 12.7), to generate a highly fluorescent product,
      thiochrome (TC). The fluorescent product was monitored by fluorimetry. A linear
      calibration graph was obtained over an ONOO- concentration range from 4.95 x 10(
      7) mol L(-1) to 2.97 x 10(-5) mol L(-1), with a detection limit of 9.78 x 10(-9)
      mol L(-1) ONOO-. The relative standard deviation at an ONOO- concentration of
      2.11 x 10(-6) mol L(-1) was 4.15% (n = 9).

PMID- 15844345
TI  - Observation of water molecules bound to a protein using cold-spray ionization
      mass spectrometry.
AB  - The characterization of water molecules bound to ribonuclease T1 (RNase T1) was
      carried out using cold-spray ionization mass spectrometry (CSI-MS). CSI-MS is a
      variant of electrospray ionization mass spectrometry (ESI-MS) operating at low
      temperature, and is particularly suitable for investigating the weaker molecular
      associations, since the temperature at the spray interface is much lower than
      that in the conventional ESI-MS. In this approach, ion peaks due to the addition
      of nine water molecules were identified at a spray temperature of 48 degrees C.
      This result showed good agreement with that inferred by the combinational
      analysis of NMR and X-ray crystallography, indicating that CSI-MS is capable of
      rapidly providing reliable information to characterize the number of water
      molecules bound to a macromolecule.

PMID- 15844346
TI  - Preparation of red blood cell column for capillary electrochromatography.
AB  - A column packed with red blood cells (RBCs) was prepared for
      electrochromatography as a separation and reaction column. RBCs were kept inside
      a piece of fused silica capillary tubing with 2% agarose gel. In the column, RBCs
      were uniformly distributed in the agarose gel matrix and their electrophoretic
      movements due to an applied voltage were suppressed well. The durability of the
      biological function of the column under applied voltage was about 1 h, although
      it could remain for 2-3 days without applied voltage. The column could not be
      used when hemolysis of the RBCs was observed in the column. When the developed
      "RBC-gel column" was used, both pyridoxamine and serotonin were converted to
      other compounds through their direct contact with RBCs.

PMID- 15844347
TI  - Flow injection chemiluminescence analysis of some penicillins by their
      sensitizing effect on the potassium permanganate-glyoxal reaction.
AB  - A new chemiluminescence method using flow injection is described for the
      determination of four penicillins, namely: phenoxymethylpenicillin potassium,
      amoxicillin, ampicillin, and ampicillin sodium. The method is based on
      sensitizing effect of these drugs on the chemiluminescence reaction of potassium
      permanganate in sulfuric acid with glyoxal. The different experimental parameters
      affecting the chemiluminescence intensity were carefully studied and incorporated
      into the procedure. The method allows the determination of 0.1-1.0 microg/ml
      phenoxymethylpenicillin potassium, 0.1-1.0 microg/ml amoxicillin, 0.1-1.0
      microg/ml ampicillin, and 0.1-1.0 microg/ml ampicillin sodium. The method was
      successfully applied to the determination of four penicillin antibiotics in
      pharmaceutical preparations.

PMID- 15844348
TI  - Determination of ambroxol in an automated multi-pumping pulsed flow system.
AB  - A new flow methodology exploiting the multi-pumping approach was developed for
      the spectrophotometric determination of ambroxol hydrochloride in pharmaceutical
      preparations. The flow manifold was implemented by using, exclusively, multiple
      solenoid-actuated micro-pumps, which acted simultaneously as sample insertion,
      solutions propelling and reagents commutation units. Linear calibration plots
      were obtained over an ambroxol concentration ranging from 10 to 200 mg l(-1)
      (r.s.d. < 0.5%, n = 15) and a sampling rate of about 60 samples per hour (flow
      rate = 1.92 ml min(-1), sample volume = 80 microl).

PMID- 15844349
TI  - Control-free air vent system for ultra-low volume sample injection on a
      microfabricated device.
AB  - An improved method of sample injection was demonstrated for introducing ultra-low
      volume liquid on a microfabricated device. In our previous study, a pressure
      driven injection method has been introduced and was applied to on-chip
      electrophoresis. In this study, the need for control of the air vent, which was
      indispensable for sample injection in the previous study, was completely
      eliminated, facilitating sample injection with great simplicity and high
      accuracy. This was realized by altering the topology of the air vent channel,
      which is connected to a hydrophobic and narrow channel (called a passive valve).
      Several types of air vent channels were designed and their injection performances
      were tested. In addition, by modifying the shape and the position of air vent
      channel and passive valve, the residual liquid volume inside the passive valve
      after sample injection was decreased to approximately 0.5% of the injected
      volume, a value which showed high reproducibility.

PMID- 15844350
TI  - Spatial resolution improvement of scanning microscopy based on thermal lens
      spectroscopy with a total-internal-reflection arrangement.
AB  - In scanning microscopy by total internal reflection with thermal lens
      spectroscopy, its spatial resolution depends on the distance between the sample
      and a converging lens, which corresponds to the objective lens in an ordinary
      optical microscope. It was found that the resolution was best when the signal
      induced by the thermal lens effect was maximum. The distance was precisely
      adjusted by monitoring the signal intensity, and the resolution became twice
      better than that previously reported. Using a shorter focal-length lens, a
      resolution of 1.9 microm was attained.

PMID- 15844351
TI  - Drug screening for influenza neuraminidase inhibitors.
AB  - Neuraminidase (NA) is one of the most important targets to screen the drugs of
      anti-influenza virus A and B. After virtual screening approaches were applied to
      a compound database which possesses more than 10000 compound structures, 160
      compounds were selected for bioactivity assay, then a High Throughput Screening
      (HTS) model established for influenza virus NA inhibitors was applied to detect
      these compounds. Finally, three compounds among them displayed higher inhibitory
      activities, the range of their IC50 was from 0.1 micromol/L to 3 micromol/L.
      Their structural scaffolds are novel and different from those of NA inhibitors
      approved for influenza treatment, and will be useful for the design and research
      of new NA inhibitors. The result indicated that the combination of virtual
      screening with HTS was very significant to drug screening and drug discovery.

PMID- 15844352
TI  - Synchronized oscillation in a modular neural network composed of columns.
AB  - The columnar organization is a ubiquitous feature in the cerebral cortex. In this
      study, a neural network model simulating the cortical columns has been
      constructed. When fed with random pulse input with constant rate, a column
      generates synchronized oscillations, with a frequency varying from 3 to 43 Hz
      depending on parameter values. The behavior of the model under periodic
      stimulation was studied and the input-output relationship was non-linear. When
      identical columns were sparsely interconnected, the column oscillator could be
      locked in synchrony. In a network composed of heterogeneous columns, the columns
      were organized by intrinsic properties and formed partially synchronized
      assemblies.

PMID- 15844353
TI  - Distributions of arsenic and essential elements in pinna of arsenic
      hyperaccumulator Pteris vittata L.
AB  - The distributions of arsenic and 6 essential elements in the pinna of As
      hyperaccumulator, Pteris vittata L., were studied using synchrotron radiation X
      ray fluorescence (SRXRF). Significant correlation between the distribution and
      mobility of the elements revealed that SRXRF study on the elemental distribution
      was feasible to inspect the transportations of elements in plants. The
      distribution of As in the pinna showed that As had great abilities to be
      transported in xylem vessels and from xylem to mesophyll. The distribution of K,
      one of the most mobile elements in plants, was similar to that of As, whereas the
      distributions of Fe and Ca with less mobility in plants were almost opposite to
      that of As in the pinna.

PMID- 15844354
TI  - Analysis of ESTs and gene expression patterns of the posterior silkgland in the
      fifth instar larvae of silkworm, Bombyx mori L.
AB  - The fibroin gene expression pattern and regulation of the posterior silkgland
      were studied by means of expressed sequence tags (ESTs) using the first and fifth
      day larvae of the fifth instar of silkworm, Bombyx mori L (strain: C 108). The
      results showed that there were 911 repetitive ESTs and 1950 single sequences
      (Singlets) among total 2861 consentient sequences, which were spliced. 1335
      sequences were identified and the other 1526 were unknown. 5560 sequences
      (55.89%) in the posterior silkgland cell of the silkworm were new ESTs without
      homology with EST data published by Mita et al. The number of repetitive ESTs and
      single sequences from the first day larvae of the fifth instar was double more
      than that of the fifth day of the same instar in the silkworms. The unigenes
      which were more than 50 in repetitive EST size (contig size) came to only about
      0.5% in total consentient sequences. There were significant differences between
      gene expression frequencies, and expressed genes were related to fibroin
      synthesis and its secretion and fibroin composition. Comparing the fifth day with
      the first day of the fifth instar, the genes-expressed quantity of fibroin heavy
      chain gene was 18 fold higher, fibroin light-chain gene 9 fold and fibroin P52
      gene 8 fold. 508 genes functioned for cellular component and 315 for enzyme after
      function tracing. These results implied that the gene expression of the first day
      was mainly for preparation for fibroin synthesis except for the growth of
      silkgland cells, and the gene expression of the fifth day of the fifth instar was
      mainly for synthesizing and excreting fibroin. Because the ratio of heavy chain,
      light chain and p25 of fibroin was not 6:6:1 as theoretically expected, or its
      special H-chain structure, the H-chain gene was not easy to detect through EST
      technique. Most of genes among total 2861 consentient sequences functioned for
      fibroin synthesis and secretion. This suggested the fibroin synthesis and
      secretion procedure of the posterior silkgland was more complex than the
      knowledge we have.

PMID- 15844355
TI  - DNA sequence comparative analysis of the 3pter-p26 region of human genome.
AB  - Most proterminal regions of human chromosomes are GC-rich and gene-rich.
      Chromosome 3p is an exception. Its proterminal region is GC-poor, and likely to
      lose heterozygosity, thus causing a number of fatal diseases. Except one gap left
      in the telomeric position, the proterminal region of human chromosome 3p has been
      completely sequenced. The detailed sequence analysis showed: (i) the GC content
      of this region was 38.5%, being the lowest among all the human proterminal
      regions; (ii) this region contained 20 known genes and 22 predicted genes, with
      an average gene size of 97.5 kb. The previously mapped gene Cntn3 was not found
      in this region, but instead located in the 74 Mb position of human chromosome 3p;
      (iii) the interspersed repeats of this region were more active than the average
      level of the whole human genome, especially (TA)n, the content of which was twice
      the genome average; (iv) this region had a conserved synteny extending from 104.1
      Mb to 112.4 Mb on the mouse chromosome 6, which was 8% larger in size, not in
      accordance with the whole genome comparison, probably because the 3pter-p26
      region was more likely to lose nucleotides and its mouse synteny had more active
      interspersed repeats.

PMID- 15844356
TI  - Ecological dynamic model of grassland and its practical verification.
AB  - Based on the physico-biophysical considerations, mathematical analysis and some
      approximate formulations generally adopted in meteorology and ecology, an
      ecological dynamic model of grassland is developed. The model consists of three
      interactive variables, i.e. the biomass of living grass, the biomass of wilted
      grass, and the soil wetness. The major biophysical processes are represented in
      parameterization formulas, and the model parameters can be determined inversely
      by using the observational climatological and ecological data. Some major
      parameters are adjusted by this method to fit the data (although incomplete) in
      the Inner Mongolia grassland, and other secondary parameters are estimated
      through sensitivity studies. The model results are well agreed with reality,
      e.g., (i) the maintenance of grassland requires a minimum amount of annual
      precipitation (approximately 300 mm); (ii) there is a significant relationship
      between the annual precipitation and the biomass of living grass; and (iii) the
      overgrazing will eventually result in desertification. A specific emphasis is put
      on the shading effect of the wilted grass accumulated on the soil surface. It
      effectively reduces the soil surface temperature and the evaporation, hence
      benefits the maintenance of grassland and the reduction of water loss in the
      soil.

PMID- 15844357
TI  - Disuccinimidyl suberate cross-linked hemoglobin as a novel red blood cell
      substitute.
AB  - Disuccinimidyl suberate (DSS) intramolecularly cross-linked hemoglobin (Hb) was
      developed as a novel red blood cell substitute. A multi-angle laser light
      scattering detector coupled with size exclusion HPLC was applied to determine the
      molecular weight of the modified Hb. SDS-PAGE was also used as a complement. It
      was proved that 83.8% of the product was intramolecularly cross-linked Hb with
      weight-average molecular weights (Mw) of 67.5 kD, 12% was dimeric Hb with Mw of
      146.6 kD, and 4.2% was trimeric Hb with Mw of 306.4 kD. The tetramer structure of
      the cross-linked Hb was stable as shown in size-exclusion chromatography using a
      mobile phase containing 1 mol/L MgCl2. Analysis by LC-MS demonstrated that the
      reaction of DSS with Hb mainly took place between the two alpha subunits within a
      Hb molecule, resulting in stabilization of the tetramer structure. However, the
      cross-linking was not site-specific. The P50 of the cross-linked Hb decreased
      from 21.8 mmHg to 14.3 mmHg, and the Hill coefficient decreased from 2.22 to
      1.41. Result of isoelectric focusing showed that the pl of DSS cross-linked Hb
      was in the range of 4.6-5.2, similar to that of serum albumin. The safety of DSS
      cross-linked Hb was favored by animal tests on rats and guinea pigs. Exchange
      transfusion experiment with DSS cross-linked Hb using rats as a model indicated
      no pressor effect or other significant side effects. The characteristics and
      properties of DSS cross-linked Hb were also compared with that of diaspirin cross
      linked Hb reported in the literature.

PMID- 15844358
TI  - Small interfering RNA-mediated inhibition of hepatitis G virus gene expression in
      human hepatoma cell Huh-7.
AB  - The RNA interference (RNAi) phenomenon is a recently observed process in which
      the introduction of a double-stranded, small interfering RNA (siRNA) into a cell
      causes the specific degradation of a homologous single-stranded RNA. It
      represents an exciting new technology that could have therapeutic applications
      for the treatment of viral infections. Since hepatitis G virus (HGV) genome is a
      positive-sense single-stranded RNA, the replication of HGV does not lead to an
      integrated DNA genome, suggesting a particularly attractive target for RNAi study
      that could eliminate viral RNA from infected cells. The eukaryotic expression
      vector pVAX.EH containing the cDNA sequences of the entire HGV structural genes
      and hygromycin resistance gene downstream from the encephalomyocarditis virus
      (ECMV) internal ribosome entry site (IRES) was constructed and transfected into
      human hepatoma cell Huh-7. The modified cleavage products of the structural
      proteins of HGV expressed in hygromycin-resistant cell line Huh-7-EH were
      confirmed by RT-PCR and Western blot methods. Two specific HGV E2 siRNAs (1-E2
      siRNA, 2-E2 siRNA) synthesized with T7 RNA polymerase by transcription in vitro
      were transfected into the Huh-7-EH cells. With the analyses of Western blot and
      the formation of hygromycin-resistant colonies, the inhibitions of expression of
      HGV structural protein by two HGV E2 siRNAs were detected and found lasting at
      least one week. The inhibition of 2-E2 siRNA was stronger and only 1% of the
      cells treated with 2-E2 siRNA formed hygromycin-resistant colonies. These results
      support that specific HGV 2-E2 siRNAs mediate the degradation of mRNA spanning
      from HGV structural gene cDNA to hygromycin resistance gene in a majority of
      cells. In conclusion, the Huh-7-EH cells expressing HGV structural proteins
      stably can be used as a cell model for studying the replication of HGV and RNAi
      and the enlargement of RNAi may exist, in mammalian cells.

PMID- 15844359
TI  - Heterodimer formation between c-Jun and Jun B proteins mediated by Epstein Barr
      virus encoded latent membrane protein 1.
AB  - Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) may trigger the
      transcription factor AP-1 including c-Jun and c-fos. In this report, using a Tet
      on LMP1 HNE2 cell line which is a dual-stable LMP1 integrated nasopharyngeal
      carcinoma (NPC) cell line and the expression of LMP1 in which could be regulated
      by the Tet-on system, we show that Jun B can efficiently form a new heterodimeric
      complex with the c-Jun protein under the regulation of LMP1, phosphorylation of c
      Jun (ser 63, ser 73) and Jun B is involved in the process of the new
      heterodimeric formation. We also find that this heterodimeric form can bind to
      the AP-1 consensus sequence. Transfection studies suggest that JNK interaction
      protein (JIP) could inhibit the heterodimer formation of c-Jun and Jun B through
      blocking the AP-1 signaling pathway triggered by LMP1. The interaction and
      function between c-Jun protein and Jun B protein increase the repertoire of
      possible regulatory complexes by LMP1 that could play an important role in the
      regulation of transcription of specific cellular genes in the process of genesis
      of nasopharyngeal carcinoma.

PMID- 15844360
TI  - Isolation of recombinant field strains of Marek's disease virus integrated with
      reticuloendotheliosis virus genome fragments.
AB  - Two Marek's disease virus (MDV) field strains were isolated from chickens with
      tumors independently from Guangdong and Guangxi provinces, and it was confirmed
      that there were no co-infections with reticuloendotheliosis viruses (REV) in
      chicken embryo fibroblast cells (CEF) in indirect fluorescence antibody test
      (IFA) with REV-specific monoclonal antibodies. By dot blot hybridization and PCR
      of genomic DNA of MDV-infected CEF, it was indicated that LTR fragments of REV
      genome were integrated into genome of these two MDV field strains. To amplify and
      clone the integrated REV LTR with MDV sequence at the junction, 4 primers from
      REV LTR and 7 primers from MDV genome fragment with REV LTR insertion hot points
      were synthesized and 28 (4x7) pairs of primers (one from REV and another from MDV
      for each pair) were used in PCR while using the genomic DNA of both strains as
      the templates. The sequence data demonstrated that both recombinant field strains
      contained the same REV LTR inserted into MDV at the identical sites in US
      fragment of the genomes. From the above, it was speculated that both recombinant
      field MDVs were originated from a same recombinant virus and spread among chicken
      flocks in two provinces.

PMID- 15844361
TI  - Production of a monoclonal antibody specific for high molecular weight glutenin
      subunits (HMW-GS) in wheat and its antigenic determinant.
AB  - Wheat high molecular weight glutenin subunits (HMW-GS) 1Bx14 and 1By15 isolated
      by preparative SDS-PAGE are used as antigen to immunize BALB/c mice. Subcutaneous
      inoculation of the antigen is performed. The intra-peritoneal injection is
      completed 3 days before fusion with myeloma cell (SP2/0) via PEG-1500. The fusion
      cells are selected by indirect enzyme-linked immuno-sorbent assay (ELISA).
      Positive hybrid cells are further verified three times by limit dilution of the
      culture cells. A hybridoma cell line is successfully obtained. The monoclonal
      antibody belongs to IgG1 subclass. In immunoblotting, the antibody binds to all
      HMW-GS of T. aestivum cultivars, but does not bind to other storage proteins in
      seeds of wheat. This result is consisting with the high homology in amino acid
      sequences among the HMW glutenin subunits in wheat. The antibody also binds to
      HMW-GS storage proteins in Aegilops squarrosa and T. durum (durum wheat).
      Furthermore, it also binds to HMW storage proteins in Secale cereale (rye),
      Hordeum vulgare (barley). However, it never binds seed storage proteins in other
      cereals such as maize, oat, rice, foxtail millet, sorghum etc. The antigen
      determinant recognized by the antibody has been located within hexapeptide
      [PGQGQQ] or / and nonapeptide [GYYPTSPQQ] in the central repetitive region of HMW
      GS.

PMID- 15844362
TI  - [Ginkgo seed food poisoning].

PMID- 15844363
TI  - [Planning and practice: simulation training for chemical disaster].

PMID- 15844364
TI  - [Disaster planning from the standpoint of fire authorities].

PMID- 15844365
TI  - [Disaster response of secondary hospitals].

PMID- 15844366
TI  - [Disaster response of tertiary hospitals].

PMID- 15844367
TI  - [Disaster planning from the standpoint of Japan Poison Information Center].

PMID- 15844368
TI  - [Problems in simulation training for chemical disasters].

PMID- 15844369
TI  - [Application of extraction needle using selective and enhanced polymer in the
      analysis of samples containing poisonous material].
AB  - Low concentrations of gas components usually need to be condensed before
      analyzing them by gas chromatography (GC). Extraction Needle using Selective and
      Enhanced Polymer (EN-SEP) is a recently developed devise for condensing the
      components that are difficult to detect by using GC. EN-SEP consists of a needle
      which contains methacrylate co-polymer. Gas components are adsorbed and condensed
      on the polymer by passing through the needle. This paper describes the usefulness
      of EN-SEP in a criminal case. EN-SEP was successfully applied to condense and
      detect a trace of propylene glycol monomethyl ether contained in a soft drink by
      using gas chromatography/mass spectrometry.

PMID- 15844371
TI  - [Current state of so-called "chemical drug"--difference between display name and
      content element].

PMID- 15844370
TI  - [Five fatalities due to inhalation of "asphyxiant gases": pathophysiological
      analysis in autopsy cases].
AB  - Five autopsy cases were examined to investigate fatal factors involved in
      inhalation of "asphyxiant gases": carbon monoxide (CO, n=3), fluorocarbons (n=1)
      and butane (n=1). In all cases, there was severe pulmonary edema and congestion
      in all viscera, suggesting advanced circulatory failure. The airway was filled
      with bloody froth in cases of fluorocarbons and butane inhalation. In CO
      intoxication, a marked increase in serum cardiac troponins suggested severe
      myocardial damage. There were also biochemical findings of respiratory distress
      (an evident increase in intra-alveolar pulmonary surfactant protein A), alveolar
      injury (an increase in serum surfactant protein A and D), rhabdomyolysis
      (myoglobinuria) and prolonged hypoxia (myogenic hyperuricemia) in cases of
      inhaling incomplete combustion gases. In a case of fluorocarbons gas inhalation,
      biochemical findings suggested respiratory distress, myocardial ischemia (an
      increase in serum CK-MB) and advanced hypoxia. Similar findings were observed in
      a case of butane inhalation, although cardiac troponin levels were low in the
      peripheral blood. These observations suggested that myocardial damage was
      prominent in CO intoxication, accompanied by respiratory distress in cases of
      inhaling incomplete combustion gases, whereas respiratory distress and hypoxia
      were major findings in cases of fluorocarbons and butane gas inhalation.

PMID- 15844372
TI  - [Practical analysis of toxic substances useful for clinical toxicology--13-
      cyanides].

PMID- 15844373
TI  - [Establishment of a new database system for human acute poisoning cases for risk
      assessment purposes].

PMID- 15844374
TI  - Delay-induced super-latent inhibition as a function of order of exposure to two
      flavours prior to compound conditioning.
AB  - A number of recent conditioned taste aversion (CTA) experiments have demonstrated
      a super-latent inhibition (LI) effect--namely, a time-induced increase in the
      effects of stimulus preexposure when the interval between acquisition and test is
      spent in a context that is different from the other experimental contexts. Two
      CTA experiments with rats were conducted to examine the role of primacy in
      producing super-LI. In Experiment 1, one of two flavours was pre-exposed,
      following which a second flavour was preexposed. After the second preexposure,
      animals were conditioned by pairing a compound of the two preexposed flavours
      with LiCl. The test stage was conducted 1 or 21 days after conditioning, with the
      interval being spent in either the same or different contexts. In the test,
      animals were confronted with two bottles, each with one of the two preexposed
      flavours. Super-LI was obtained only for the first preexposed flavour in the 21
      day delay group that spent the interval in a different context. Experiment 2 was
      designed to ensure that the effects in Experiment 1 represented LI, and to
      control for order of presentation of the flavours and time between preexposure
      and acquisition. The results replicated those of Experiment 1. The two
      experiments support the importance of primacy in the general super-LI experiment
      where CS-alone preexposure precedes CS-US.

PMID- 15844375
TI  - Acquisition of instrumental conditioned reinforcement is resistant to the
      devaluation of the unconditioned stimulus.
AB  - The associative mechanisms responsible for the efficacy of Pavlovian stimuli
      during first- and second-order conditioning have been extensively studied, but
      little is known about the representations underlying instrumental conditioned
      reinforcement. The present study investigated the associative structure
      underlying conditioned reinforcement, by employing an unconditioned stimulus (US)
      devaluation procedure on a commonly used instrumental task: the acquisition of a
      new response with conditioned reinforcement. Whilst US-directed behaviour was
      abolished following devaluation, the conditioned stimulus acting as a conditioned
      reinforcer supported the acquisition of instrumental responding. In this
      preparation then, the conditioned reinforcer appears to be impervious to
      devaluation of its associated US, suggesting that the underlying representation
      maintaining behaviour is independent of the current value of the US and may
      reflect the activation of a central appetitive motivational state.

PMID- 15844376
TI  - The perception of empty and filled time intervals by pigeons.
AB  - Pigeons were trained in a within-subjects design to discriminate durations of a
      filled interval (2 s and 8 s of light) and durations of an empty interval (2 s
      and 8 s bound by two 500-ms light markers). Filled intervals required a response
      to one set of comparisons (e.g., blue vs. yellow), whereas empty intervals
      required a response to a different set of comparisons (e.g., red vs. green).
      Psychophysical testing indicated that empty intervals were judged to be longer
      than equivalent durations of a filled interval. This finding was replicated when
      the anchor durations used during training were changed to 1 s and 4s, or 4s and
      16s. The difference between the point of subjective equality (PSE) for the empty
      intervals and the PSE for filled intervals increased as the magnitude of the
      anchor duration pairs increased. In addition, the difference limens (DL) for
      empty intervals were smaller than those for filled intervals, and they also
      increased as the magnitude of anchor duration pairs increased. An analysis of the
      Weber fractions (WF; i.e., DL/PSE) provided evidence for superimposition of the
      empty and filled timing functions across the different sets of anchor durations.
      These results suggest that the accumulation of subjective time was greater for
      empty intervals than for filled intervals. Within the framework of scalar timing
      theory, this difference in timing appeared to be the result of a clock rate
      difference rather than a switch latency difference.

PMID- 15844377
TI  - Flavour liking and preference conditioned by caffeine in humans.
AB  - When caffeine consumers repeatedly experience a novel flavoured drink containing
      caffeine, the rated pleasantness of the drink flavour increases progressively.
      These results could be interpreted in terms of the flavour acting as a Pavlovian
      conditioned stimulus (CS) predicting the consequences of caffeine ingestion.
      However, all studies of this phenomenon to date have used between-subjects
      designs, and one criticism of this is that changes in pleasantness might have
      arisen from nonspecific effects. A more rigorous test is to examine changes in
      pleasantness for two drinks, a CS+ flavour paired with caffeine and CS- paired
      with placebo. Accordingly, 20 moderate caffeine consumers consumed both CS+ and
      CS- drinks in counterbalanced order over eight conditioning trials at breakfast,
      with hedonic and sensory characteristics evaluated on each trial. As predicted,
      the rated pleasantness of the CS+ drink increased whereas pleasantness of the CS-
      drink did not change. Despite this, participants did not have an overall
      preference for the CS+ flavour posttraining. However, both those who chose the
      CS+ and those who chose the CS- at the end showed the same direction and rate of
      change in pleasantness for the two drinks during training, but spurious
      differences in baseline preference obscured this effect in terms of an overall
      change in preference. Overall these data suggest that changes in pleasantness of
      drinks paired with caffeine delivery are best explained in terms of Pavlovian,
      associations between drink flavour and the postingestive effects of caffeine.

PMID- 15844378
TI  - The role of context in the inhibitory conditioning of honeybees.
AB  - Conditioned inhibition or CI training (A+/AB-) was compared with S- training
      (A+/B-) in three experiments on proboscis-extension conditioning in harnessed
      honeybees. The purpose was to test the Rescorla-Wagner assumption, widely
      credited in the vertebrate literature, that a nonreinforced stimulus acquires
      inhibitory properties in proportion to the excitatory value of the context in
      which it is presented. In prior work with free-flying honeybees pretrained with
      sucrose to come of their own accord to the experimental situation, no differences
      were found in the consequences of CI and S- training, perhaps because A added
      little to the excitatory value of the context (already very high) in which B
      occurred. In the new experiments, with harnessed subjects brought involuntarily
      into the training situation, negative results again were obtained. The
      possibility is considered that inhibitory conditioning in honeybees is
      independent of the excitatory value of the context.

PMID- 15844379
TI  - Transfer of spatial behaviour controlled by a landmark array with a distinctive
      shape.
AB  - In two experiments, rats swam to a submerged platform in one corner of a
      rectangular or kite-shaped array created by four identical landmarks attached to
      the walls of a circular pool. After training in the rectangular array, rats
      expressed a preference for the corner in the kite-shaped array that was
      geometrically equivalent to where the platform was located previously. After
      training in either array, the removal of two landmarks from the rectangular
      array, or the landmark at the apex of the kite-shaped array, did not affect the
      control over searching exerted by the remaining landmarks. The results imply that
      rats use local rather than global spatial representations when searching for a
      hidden goal with reference to an array of landmarks.

PMID- 15844380
TI  - Acute renal failure.
AB  - Acute renal failure (ARF) can be defined as the sudden loss of adequate renal
      function to clear metabolic wastes and maintain normal fluid and electrolyte
      balance. ARF may occur in otherwise healthy children, may complicate underlying
      chronic kidney disease, or may result from multiorgan disorders. The underlying
      cause of the renal injury remains the major factor that determines outcomes for
      patients with ARF. Overall mortality in children with ARF varies from 8% to 89%,
      with greater than 50% mortality associated with three-organ system failure.
      Management of the adolescent with ARF ranges from conservative management in mild
      cases to more intensive care in hospitalized patients with complications of fluid
      overload, hypertension, metabolic acidosis, or life-threatening hyperkalemia.

PMID- 15844381
TI  - Hypertension in adolescents.
AB  - BP elevation in adolescence may be the first clue to underlying renal or other
      organ-system pathology, or it may be simply a warning sign of future
      cardiovascular risk. Careful measurement of BP and thorough evaluation of
      adolescents with sustained BP elevation should make possible the identification
      of those who require treatment. Usually a combination of pharmacologic and
      nonpharmacologic measures will result in satisfactory control of hypertension
      while permitting a normal quality of life.

PMID- 15844382
TI  - Nephrotoxicity of over-the-counter analgesics, natural medicines, and illicit
      drugs.
AB  - Toxic nephropathy is a disorder whose primary feature is impairment of the normal
      functions of the kidney. The clinical manifestations of toxic nephropathy vary
      from a mild reduction in renal function to hematuria, proteinuria, and
      urolithiasis to a severe progressive toxicity culminating in end-stage renal
      disease. Although it is commonplace for adolescents to use supplemental
      treatments such as natural medicines and over-the-counter (OTC) analgesics, they
      do not often reveal the use of such treatments to physicians, nor do they fully
      understand their potential adverse effects. This article reviews the nephrotoxic
      effects of OTC analgesics, natural medicines, and illicit drugs.

PMID- 15844383
TI  - Renal manifestations of sexually transmitted diseases: sexually transmitted
      diseases and the kidney.
AB  - The adolescent population is particularly vulnerable to STDs. Those that cause
      significant kidney disease are of viral origin. The primary VVD are HIV-1, HBV,
      and HCV. Screening of high-risk populations should include quantitation of
      proteinuria, including total protein and microalbumin, to assess severity of
      renal damage and potential for progression. Renal biopsy is indicated for
      diagnosis and for planning important treatment interventions if there is
      significant proteinuria or decreased renal function. Causes of acute renal
      failure are frequently reversible and should be treated aggressively. These
      include HUS, vaso-motor or ischemic acute tubular necrosis, and drug toxicities.
      The spectrum of chronic kidney disease associated with VVD is broad and may
      include systemic manifestations of vasculitis. HIV-associated nephropathy is the
      prototype, with the most prevalent lesion remaining FSGS. Progression occurs in
      up to 15% of the patients, who are overwhelmingly of African lineage. Significant
      advances in management include ongoing development of HAART, angiotensin
      antagonists to control proteinuria, and novel immune-modulating drugs such as
      MMF, CsA, and rituximab. Dialysis therapies have offered improved survival,
      especially in pediatric patients. Moreover, transplantation is no longer
      considered experimental and should be offered to select patients.

PMID- 15844384
TI  - Glomerulonephritis.
AB  - GN in the adolescent requires prompt diagnosis. When even mild degrees of renal
      insufficiency are documented, immediate referral to a nephrologist is necessary
      to ensure that serious conditions, such as RPGN, are correctly diagnosed and
      aggressively managed. In an adolescent with macroscopic hematuria, the
      demonstration of dysmorphic RBCs, RBC casts, and proteinuria indicates that the
      bleeding is of glomerular origin. Physicians caring for adolescents with chronic
      GN should have a basic understanding of the specific disorders. They may be
      involved in blood pressure monitoring and should be aware of the potential side
      effects of the antihypertensive and immunosuppressive medications used in
      patients with GN.

PMID- 15844385
TI  - Urolithiasis in adolescent children.
AB  - Idiopathic urolithiasis in children has become more frequent in the past few
      decades as a result of increasing affluence and rapid change in our society's
      dietary habits. In Western societies, calcium stones in the kidney and ureter
      predominate. Pediatric urolithiases, unlike the adult form, require a
      comprehensive metabolic evaluation, because metabolic and enzymatic derangements
      play an important role in their pathogenesis. The recent advancements in
      endoscopic procedures, interventional radiology, and lithotripsy have allowed
      children to be managed effectively without open surgery. Pediatric urolithiasis
      requires a close working relationship between the urologist for acute surgical
      management of urolithiasis and the nephrologists for prevention of stone
      formation. In many children and adolescents with urolithiasis, a nonpharmacologic
      approach involving the adoption of healthy nutrition habits may suffice.

PMID- 15844386
TI  - Kidneys and sports.
AB  - With better understanding of the nature of renal disease and its treatment, many
      more adolescents are now allowed to participate in recreational and competitive
      sports. The positive physiologic and psychological effects of exercise are
      increasingly being appreciated in adolescents with chronic diseases. This article
      reviews relevant aspects of renal disease that have implications for sports
      participation by adolescents, including hematuria, proteinuria, hyponatremia,
      hypertension, solitary kidney, exercise-related acute renal failure, and
      chronic/end-stage renal disease. It also reviews the renal effects of creatine
      and protein supplementation in athletes.

PMID- 15844388
TI  - Urinary tract infections among adolescents.
AB  - UTIs occur quite frequently among adolescent females. In the vast majority of
      these patients, UTIs are uncomplicated infections and are not suggestive of
      underlying anatomic abnormality of the urinary tract. A UTI in an adolescent
      female is suggestive, however, of sexual debut. A small number of adolescent
      males suffer from UTI annually; in at least half of such cases, there is likewise
      no underlying urinary anomaly. Because of the symptomatic overlap and high
      prevalence of STI in adolescents, the clinician must have a high index of
      suspicion for STI in any adolescent presenting with urinary symptoms.

PMID- 15844387
TI  - Cancer and the kidney.
AB  - This article provides a summary of renal cancers that can affect adolescent
      patients. It encompasses both isolated and syndrome-associated cancers and the
      various renal complications associated with cancer therapy. Prompt recognition
      and appropriate referral and management, along with periodic long-term follow-up,
      will enhance both the survival and quality of life of young people afflicted with
      these serious diseases.

PMID- 15844389
TI  - Adolescents with proteinuria and/or the nephrotic syndrome.
AB  - Persistent proteinuria of various degrees of severity in adolescents should be
      regarded seriously, because recent evidence points to this abnormality's being
      associated with chronic kidney disease. However, it is also important for primary
      care physicians to be aware that most adolescents who are found to have
      proteinuria on a screening urinalysis do not have renal disease, and the
      proteinuria will usually resolve on repeat testing. Appropriate measures to
      determine whether the proteinuria is fixed and not orthostatic can and should be
      conducted expeditiously, because they will allay stress for most patients. For
      the minority of patients in whom more serious forms of proteinuria exist, timely
      consultation with a pediatric nephrologist is recommended.

PMID- 15844390
TI  - Diabetes mellitus and the kidney in adolescents.
AB  - Diabetic nephropathy continues to be a major complication of both types I and II
      diabetes; renal disease in the two types of diabetes exhibits no major
      differences with regard to initiation, progression, or treatment. The increasing
      prevalence of type II diabetes among adolescents means that understanding
      diabetic nephropathy and its prevention and treatment strategies is increasingly
      important for physicians caring for this population. The most important
      prevention and treatment modalities for diabetic nephropathy are improved
      glycemic control and aggressive blood pressure control, beginning as soon as
      possible after the diagnosis of diabetes.

PMID- 15844391
TI  - Chronic kidney disease in adolescents.
AB  - Chronic kidney disease (CKD) involves a fixed deficit or progressive
      deterioration in kidney function, producing variable losses of normal physiologic
      functions. In adolescents, CKD results from a wide range of causes. Because of
      the broad spectrum of disease, the physician providing primary care to the
      adolescent must be knowledgeable about findings leading to the diagnosis of CKD
      and must understand the physiologic basis for therapeutic management.
      Complications of normal renal function loss include issues of fluid, electrolyte,
      and acid-base balance, as well as development of anemia, cardiovascular disease,
      metabolic bone disease, and growth failure. Goals of therapy include anticipation
      and replacement of lost physiologic functions so that the adolescent can grow and
      develop normally.

PMID- 15844392
TI  - Renal transplantation in adolescents.
AB  - Renal transplantation remains the goal for the pediatric patient with end-stage
      renal disease. Recent advances in technology and immunosuppression have greatly
      enhanced patient and graft survival, while reducing significant complications.
      However, transplantation of adolescents is still fraught with the potential for
      serious problems. The increased risk of graft loss, late acute rejection, and
      incomplete rejection reversal observed in the adolescent age group demands
      further investigation. Lack of adherence to immunosuppression regimens may be an
      important contributory factor. Strategies to address the unique concerns of this
      high-risk population, including the use of a multidisciplinary team, are
      essential to improving outcomes.

PMID- 15844393
TI  - Adolescent urology.
AB  - The area of adolescent urology encompasses a period of development that coincides
      with puberty. Disorders seen during this time either carry over from childhood
      (eg, hydronephrosis, enuresis, voiding dysfunction) or are early manifestations
      of urologic problems seen more commonly in adulthood (eg, urolithiasis,
      varicoceles). This article focuses on several areas of urology common to the
      adolescent.

PMID- 15844394
TI  - Hematuria in adolescents.
AB  - Hematuria is not a rare finding during adolescence. The high prevalence of
      microscopic hematuria is not surprising when one considers the vast number of
      ways in which RBC can end up in the urine. The adolescent presenting with gross
      hematuria, proteinuria, or microscopic hematuria in combination with other
      symptoms of genitourinary disease is more likely to require a therapeutic
      intervention than is the individual found incidentally to have microscopic
      hematuria. Screening for hematuria is not supported by current evidence. When it
      is discovered as the result of a screening examination, persistent microscopic
      hematuria in an otherwise asymptomatic individual may not require further
      investigation; however, the renal ultrasound examination has little risk and is
      helpful in diagnosing many of the conditions amenable to intervention. Serum
      studies offer little useful information in the evaluation of microscopic
      hematuria. Addressing isolated hematuria in a systematic, evidence-based fashion
      can help avoid untoward patient and parental worry and excessive health care
      costs, without missing treatable or progressive disease entities.

PMID- 15844395
TI  - Validity of the Eating Attitudes Test: a study of Mexican eating disorders
      patients.
AB  - OBJECTIVE: To evaluate the psychometric properties of the Mexican version of the
      Eating Attitudes Test (EAT-40) in clinical and control populations in Mexico
      City. METHOD: 276 female patients with eating disorders [52 with anorexia nervosa
      (AN), 102 with bulimia nervosa (BN) and 122 with eating disorders not otherwise
      specified (EDNOS)] and a comparison group of 280 normal control female subjects
      completed the EAT. RESULTS: The EAT had an adequate level of internal consistency
      in the clinical sample (Cronbach's alpha=0.90). Total score was significantly
      correlated with criterion group membership (r=0.77, p< or =0.0001), suggesting a
      high level of concurrent validity. There was a small overlap in the frequency
      distribution of the 2 groups (eating disorders and control) and only 6% of the
      normal controls scored as high as lowest anorexic and bulimic patients. The
      factorial analysis yielded five factors accounting for 46.6% of total variance:
      1) Dietary restraint, 2) Bulimia, 3) Drive of thinness, 4) Food preoccupation and
      5) Perceived social pressure. CONCLUSIONS: This study provides evidence that the
      Mexican version of the EAT is an economical, reliable and potentially useful
      instrument for research in this field.

PMID- 15844396
TI  - Predictive factors of social disability in anorexic and bulimic patients.
AB  - OBJECTIVES: The purpose of this study was to determine whether subjects suffering
      from anorexia nervosa (AN) or bulimia nervosa (BN) would demonstrate more severe
      social disability than a control group; and whether social disability could be
      best explained as a function of the eating disorder itself or as a function of
      comorbid anxiety or depressive disorders. METHOD: Subjects were 166 AN subjects,
      105 BN subjects and 271 control subjects matched for age, sex and socio-economic
      status. Prevalence of anxiety or depressive disorders was assessed (through the
      Mini International Neuropsychiatric Interview), and social functioning was
      measured (through the Groningen scale). RESULTS: The majority of AN and BN
      subjects demonstrated social disability in the "social role" (leisure time, time
      spent with friends) and the "occupational role" (work or educational activities).
      A regression analysis was employed to uncover predictive factors of social
      disability. Eating disorders (AN and BN), anxiety disorders and depression
      accounted for a large portion of social disability. DISCUSSION: Anxiety and
      depressive disorders appear to play an important role in the type of social
      disability demonstrated in eating disorder patients. Therapeutic implications are
      discussed.

PMID- 15844397
TI  - Eating disturbances in siblings of patients with eating disorders.
AB  - OBJECTIVE: The purpose of this study was to investigate whether siblings of
      patients with eating disorders show a more disturbed eating behavior and a higher
      proneness to associated psychological characteristics than controls. METHOD: 84
      patients with eating disorders of an outpatient clinic, their siblings (n=84) and
      a control group (n=84) with an age range 14-34 for the total sample were
      evaluated using the Eating Disorder Inventory-2. RESULTS: There was no
      significant difference between the siblings and the controls in disturbed eating
      behavior. DISCUSSION: The existence of an eating disorder in patients does not
      seem to be related to the development of eating disturbed behavior in their
      siblings.

PMID- 15844398
TI  - Panic-agoraphobic spectrum in obese binge eaters.
AB  - OBJECTIVE: This study investigated the frequency of the panic-agoraphobic
      spectrum symptoms in a sample of obese subjects affected by Binge Eating Disorder
      (BED) vs controls. METHOD: Fifty obese with BED were matched by age, sex and
      marital status to twenty-five normal weight controls. The Structured Clinical
      Interview For Panic-Agoraphobic Spectrum--SCI-PAS was administered to all
      participants. RESULTS: Obese subjects with BED presented significantly higher
      frequencies of typical and atypical panic symptoms (82% vs 8%, p<0.0001),
      agoraphobia (58% vs 12%, p=0.002) and reassurance orientation (56% vs 8%,
      p=0.001) than controls. DISCUSSION: BED frequently co-occurs with other major
      psychiatric disorders, traditionally assessed using categorical methods of
      classification of mental disorders. The spectrum of the subthreshold, atypical
      and partial symptoms of full-blown mental disorders, often neglected by
      categorical approach, may also affect subjective well-being and functioning as
      full-blown disorders. The identification of the subthreshold symptomatology may
      have relevant implications for the response to treatment and the outcome of the
      eating disorder.

PMID- 15844399
TI  - The significance of routine laboratory analyses in the assessment of teenage
      girls with eating disorders and weight loss.
AB  - Routine laboratory investigations that had been performed at disease assessment
      on 327 teenage girls with eating disorders and weight loss were analyzed. The
      laboratory investigations included erythrocyte sedimentation rate (ESR), blood
      haemoglobin concentration (Hb), white blood cell count (WBC), platelet count,
      serum alkaline phosphatase (ALP) activity, serum aspartate aminotransferase
      (ASAT) activity, serum alanine aminotransferase (ALAT) activity, serum albumin
      concentration, glycated haemoglobin (HbA1c) and serum concentrations of sodium,
      potassium, magnesium, calcium (corrected for albumin), inorganic phosphate,
      creatinine and urea. The results were for ESR, Hb, WBC, platelet count, ALP,
      ASAT, ALAT, inorganic phosphate, creatinine, urea and HBA1C related to weight and
      (ongoing) weight loss. The variations of the biochemical measurements were,
      however, largely within reference ranges, weight and weight changes predicted the
      biochemical measurements only to a small degree and in individual patients the
      results of the analyses often suggested normality. These analyses may therefore
      not be suited to assess the degree of weight loss and starvation in eating
      disorders. They may, however, be useful for the exclusion of other diseases which
      could show weight loss and biochemical abnormalities.

PMID- 15844400
TI  - Socio-economic variables and eating disorders: a comparison between patients and
      normal controls.
AB  - OBJECTIVE: Previous research demonstrates that the relationship between socio
      economic status (SES) and eating disorders is not consistent. The present study
      compares SES and demographic factors among Swedish women, randomly drawn from the
      population register and female patients seen for treatment. METHOD: 223
      consecutive eating disorder patients (ED) between 18 and 24 years of age
      (anorexia, n=26, bulimia, n=127, Eating disorder not otherwise specified, n=70)
      were compared with 750 normal controls (CONT) between 18 and 24 years of age.
      Both groups were assessed using the same questionnaire regarding SES and
      demographic factors. RESULTS: ED's have a higher SES background and live in more
      privileged socio-demographic areas than CONT. ED's have lower social status, have
      more separations, and are more often single than CONT. CONCLUSION: These data
      demonstrate a connection between high socio-economic and demographic data, low
      social status and eating disorder patients compared to normal controls.

PMID- 15844401
TI  - Disordered eating attitudes and behaviours in the high-school students of a rural
      Canadian community.
AB  - BACKGROUND: Most surveys of disordered eating attitudes in teenagers target
      females in urban areas. To help plan the distribution of treatment resources for
      eating disorders in British Columbia we studied male and female students in all
      of the high schools of a rural community. METHODS: Three hundred and ninety-six
      of the 2,589 students attending the four high schools within the rural community
      completed the EAT-26 and a demographic questionnaire. RESULTS: Three hundred and
      eighty-one of the 396 students (96%) satisfactorily completed and returned the
      survey. Their ages ranged from 12 to 19 years with a mean of 15.2 years (SD=1.5
      years). Fifty-nine percent of participants were female. On average, males wanted
      to be 6.2 kg (SD=1.2 kg) heavier and females wanted to be 2.8 kg (SD=6.5 kg)
      lighter and 8.3 percent of males and 17.3 percent of females scored twenty or
      above on the EAT-26. INTERPRETATION: The prevalence of disordered eating
      attitudes and behaviours in this rural setting was similar to that reported in
      urban communities in Canada. Disordered eating attitudes and behaviours were
      common in males. We conclude that there is need for treatment resources for males
      and that the need for treatment is as great in rural as urban communities.

PMID- 15844402
TI  - Incidental learning of food and emotional words in women with anorexia nervosa.
AB  - Prior research suggests that anorexic patients show a memory bias for fattening
      foods when they are processed in depth or with reference to the self. The present
      study examined whether anorexic subjects exhibit a bias for fattening foods when
      these are presented as task-irrelevant distractor stimuli. It also investigated
      whether anorexic patients pay less attention to emotion stimuli. A sequential
      word-word evaluation task was administered to 11 inpatients with anorexia nervosa
      and 11 non-dieting normal subjects. There were four types of distractor words:
      high caloric foods, positive, negative, and neutral. Anorexic patients recalled
      no more food words but fewer neutral and positive words than normal subjects. The
      present data suggest that, compared to healthy young women, anorexic patients
      show no memory bias for fattening foods when these data are presented as
      peripheral environmental information. Anorexic patients are perceptually no less
      sensitive to negative emotional information than normal subjects.

PMID- 15844403
TI  - Physical and psychological factors influencing heart rate variability in anorexia
      nervosa.
AB  - OBJECTIVE: The aim of this study was to determine which physical and
      psychological factors influence the autonomic nervous system (ANS) of patients
      with anorexia nervosa (AN). METHODS: The subjects were 14 AN patients and 12
      healthy controls. Beat to beat heart rate variability recorded in a supine
      position with a controlled respiratory rate of 15/min, was analyzed using power
      spectral analysis. Symptoms of anxiety and depression were assessed by State and
      Trait Anxiety Inventory and Zung's Self-rating Depression Scale respectively.
      RESULTS: Anxiety had a significant negative correlation with the ANS of AN
      patients. The illness duration times body mass index (BMI), a measure of
      sustained extreme loss of weight, was also significantly associated with changes
      in the ANS of AN patients. CONCLUSION: Although the ANS is influenced by various
      factors, sustained extreme loss of weight seems to be more influential factor in
      AN patients.

PMID- 15844405
TI  - British Columbia Provincial Eating Disorders Program: an organizational
      description.
AB  - The British Columbia Provincial Eating Disorders Program (BCEDP) is a small
      government funded body that communicates eating disorder treatment needs to the
      government, helps communication between primary, secondary, and tertiary care
      givers, gives treatment advice and teaching to primary and secondary care givers,
      and assists the Provincial Eating Disorders Resource Centre in decision making
      and communication with government. The program deals with anorexia nervosa and
      bulimia nervosa, but not obesity, for budgetary reasons.

PMID- 15844404
TI  - Which factors do provoke binge eating? An exploratory study in eating disorder
      patients.
AB  - OBJECTIVE: To study the different factors (external, emotional, cognitive, and
      physiological) which may trigger binge eating in eating disorder patients and to
      make a comparison of binge eating triggers in different eating disorder samples,
      i.e. anorexia nervosa bingeing-purging type and bulimia nervosa (BN). METHOD: A
      total of 242 eating disorder patients filled out the Binge Eating Trigger
      Checklist (BETCH), a new screening device to evaluate the type of situations (and
      their experienced discomfort) which subjects identify as antecedents of a binge
      eating episode. RESULTS: Eating disorder patients report a combination of
      negative emotions, physiological states (urge for sweets) and negative cognitions
      as most important antecedents for their bingeing episodes. External stimuli were
      only reported by a small number of patients and provoked significantly lower
      levels of discomfort. A comparison of binge eating triggers in bingeing anorexia
      nervosa patients and bulimic patients showed only a few significant differences.
      CONCLUSIONS: Binge eating, as perceived and reported by eating disorder patients,
      seems to be provoked by a combination of different antecedents, both emotional,
      cognitive and physiological. Remarkably enough, binge eating triggers did not
      differ between bingeing anorectic patients and patients suffering from BN.

PMID- 15844406
TI  - Growing concern about bird flu sparks call for global action.

PMID- 15844407
TI  - The ProHeart debate.

PMID- 15844408
TI  - Screening and early detection. Veterinarians underuse human health care
      prevention tactics.

PMID- 15844409
TI  - Is there a common theme in the alternative medicine debate?

PMID- 15844410
TI  - Is there a common theme in the alternative medicine debate?

PMID- 15844411
TI  - Is there a common theme in the alternative medicine debate?

PMID- 15844412
TI  - Is there a common theme in the alternative medicine debate?

PMID- 15844413
TI  - Is there a common theme in the alternative medicine debate?

PMID- 15844414
TI  - Disappointed in quality-of-life article.

PMID- 15844415
TI  - Veterinarian's nomination to FDA applauded.

PMID- 15844416
TI  - What is your diagnosis? Primary tracheal tumor.

PMID- 15844417
TI  - What is your diagnosis? Chondrosarcoma.

PMID- 15844418
TI  - Compendium of animal rabies prevention and control, 2005.

PMID- 15844420
TI  - Autochthonous visceral leishmaniasis in dogs in North America.

PMID- 15844419
TI  - Use of bovine single nucleotide polymorphism markers to verify sample tracking in
      beef processing.
AB  - OBJECTIVE: To determine whether a selected set of 20 single nucleotide
      polymorphism (SNP) markers derived from beef cattle populations can be used to
      verify sample tracking in a commercial slaughter facility that processes
      primarily market (ie, culled) dairy cows. DESIGN: Prospective, blinded validation
      study. ANIMALS: 165 cows and 3 bulls from 18 states (82% Holstein, 8% other dairy
      breeds, and 10% beef breeds). PROCEDURE: Blood was collected by venipuncture from
      randomly chosen animals just prior to slaughter. The purported corresponding
      liver samples were collected during beef processing, and genotype profiles were
      obtained for each sample. RESULTS: On the basis of SNP allele frequencies in
      these cattle, the mean probability that 2 randomly selected individuals would
      possess identical genotypes at all 20 loci was 4.3 x 10(-8). Thus, the chance of
      a coincidental genotype match between 2 animals was 1 in 23 million. Genotype
      profiles confirmed appropriate matching for 152 of the 168 (90.5%) purported
      blood-liver sample pairs and revealed mismatching for 16 (9.5%) pairs. For the 16
      mismatched sample pairs, 33% to 76% of the 20 SNP genotypes did not match (mean,
      52%). Discordance that could be attributed to genotyping error was estimated to
      be < 1% on the basis of results for split samples. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that this selected set of 20 bovine SNP markers is
      sufficiently informative to verify accuracy of sample tracking in slaughter
      plants that process beef or dairy cattle. These or similar SNP markers may
      facilitate high-throughput, DNA-based, traceback programs designed to detect drug
      residues in tissues, control of animal diseases, and enhance food safety.

PMID- 15844421
TI  - Animal agriculture and the welfare of animals.

PMID- 15844422
TI  - My responsibilities as a swine caregiver.

PMID- 15844423
TI  - Sow housing: opportunities, constraints, and unknowns.
AB  - As Webster has stated, we have real opportunities to provide incremental
      improvements to a whole range of welfare factors. We need a disciplined approach
      that takes into account the skills of farmers, veterinarians, and the whole range
      of other specialists involved in animal agriculture. Improvement is best based on
      a model of discovery, transparency, and dialogue. Combative models impede
      discovery and dialogue, and the animals are the most likely to suffer when we
      create such a scenario. Veterinarians have a real opportunity to aid swine farms
      in identifying opportunities and allowing for a transparent portrayal of
      activities on the farm.

PMID- 15844424
TI  - Welfare challenges in sow housing.

PMID- 15844425
TI  - Experiences with alternative methods of sow housing.

PMID- 15844426
TI  - Sow housing: science, behavior, and values.

PMID- 15844427
TI  - Serologic survey of cats and dogs during an epidemic of West Nile virus infection
      in humans.
AB  - OBJECTIVE: To estimate West Nile virus (WNV) infection rates, assess
      environmental variables that correlated with seropositivity in dogs and cats, and
      assess whether pets should be considered as possible sentinels for WNV and
      therefore of potential human exposure. DESIGN: Cross-sectional serosurvey.
      ANIMALS: 442 dogs and 138 cats. PROCEDURE: Serum samples were screened for
      seropositivity against WNV by use of the plaque reduction neutralization test.
      RESULTS: 116 (26%) dogs and 13 (9%) cats yielded positive results. The odds of
      seropositivity against WNV for outdoor-only family dogs were almost 19 times as
      great as those for indoor-only family dogs and almost twice as great for stray
      dogs as for family dogs. Family dogs not receiving heartworm medication were 2.5
      times as likely to yield positive results for antibodies against WNV as family
      dogs receiving heartworm medication. CONCLUSIONS AND CLINICAL RELEVANCE:
      Seropositivity was greater for outdoor family dogs than for indoor family dogs.
      Further investigation of the potential use of stray dogs as sentinel indicators
      for WNV infection and the potential risk of human exposure is warranted.

PMID- 15844428
TI  - Validity of a health-related quality-of-life scale for dogs with signs of pain
      secondary to cancer.
AB  - OBJECTIVE: To develop and validate a health-related quality-of-life scale for
      dogs with pain secondary to cancer. DESIGN: Questionnaire development. ANIMALS:
      40 healthy dogs with no history or signs of pain, 20 dogs with dermatologic
      disease but no signs of pain other than mild pruritus, and 20 dogs with cancer.
      PROCEDURE: Owners of all dogs completed a questionnaire containing 12 questions
      with 4 options for each question, and a quality-of-life score ranging from 0 to
      36 was calculated. Scores for dogs with cancer were compared with scores for
      healthy dogs and dogs with dermatologic disease. RESULTS: All owners indicated
      that the questionnaire was easy to complete. Scores for healthy dogs were
      significantly different from scores for dogs with cancer and scores for dogs with
      dermatologic disease. Scores for dogs with dermatologic disease were
      significantly different from scores for dogs with cancer. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that a simple questionnaire may be useful
      in assessing health-related quality of life in dogs with pain secondary to
      cancer, in that dogs with cancer had significantly lower scores than did healthy
      dogs and dogs with dermatologic disease.

PMID- 15844429
TI  - Hindbrain decompression in a dog with scoliosis associated with syringomyelia.
AB  - A 6-month-old female Border Collie was examined because of a 1-month history of
      progressive curvature of the cervical portion of the vertebral column.
      Radiography revealed severe cervical and thoracic scoliosis. Cervical
      syringomyelia and hydrocephalus were observed by means of magnetic resonance
      imaging. Suboccipital craniotomy and laminectomy of the first cervical vertebra
      were performed, and substantial improvement in the scoliosis and syringomyelia
      was observed 3 months after surgery. No recurrences were seen during the first
      year after surgery.

PMID- 15844430
TI  - Incidence and prognostic importance of lymph node metastases in dogs with
      appendicular osteosarcoma: 228 cases (1986-2003).
AB  - OBJECTIVE: To determine the incidence of regional lymph node metastasis in dogs
      with appendicular osteosarcoma and determine whether regional lymph node
      metastasis was associated with shortened disease-free interval or survival time.
      DESIGN: Retrospective study. ANIMALS: 228 dogs with appendicular osteosarcoma in
      which regional lymph nodes were examined histologically at the time of limb
      amputation. PROCEDURE: Information collected from the medical records included
      signalment; affected site; initial serum alkaline phosphatase activity; whether
      treatment involved adjuvant chemotherapy and, if so, chemotherapeutic agents
      administered and number of treatments; disease-free interval; and survival time.
      RESULTS: 10 (4.4%) dogs had histologic evidence of regional lymph node metastasis
      at the time of amputation. Median disease-free interval for dogs without regional
      lymph node metastasis (238 days; range, 0 to 1,067 days) was significantly longer
      than median disease-free interval for dogs with regional lymph node metastasis
      (48 days; range, 2 to 269 days). Median survival time for dogs without lymph node
      metastasis (318 days; range, 20 to 1,711 days) was significantly longer than
      median survival time for dogs with lymph node metastasis (59 days; range, 19 to
      365 days). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that regional
      lymph node metastasis is rare in dogs with appendicular osteosarcoma but that
      dogs with lymph node metastasis have a poorer prognosis than do dogs without.

PMID- 15844431
TI  - Outcome of dogs with mast cell tumors in the inguinal or perineal region versus
      other cutaneous locations: 124 cases (1990-2001).
AB  - OBJECTIVE: To compare clinical outcome of dogs with cutaneous mast cell tumors
      (MCTs) in the inguinal or perineal region with outcome for dogs with MCTs in
      other cutaneous locations. DESIGN: Retrospective study. ANIMALS: 37 dogs with
      MCTs in the inguinal or perineal region and 87 dogs with MCTs in other cutaneous
      locations. PROCEDURE: Information obtained from the medical records included sex,
      breed, age, histologic grade of all tumors, number and location of all tumors,
      tumor size (ie, diameter of the tumor), completeness of surgical excision,
      treatments administered in addition to surgery, and outcome. In all dogs, the
      primary treatment consisted of surgical excision. RESULTS: Disease-free interval
      and survival time for dogs with MCTs in the inguinal or perineal region were not
      significantly different from values for dogs with MCTs in other cutaneous
      locations. Dogs with incompletely excised tumors, dogs with grade III tumors, and
      dogs that received systemic treatment were 2, 2.5, and 4 times as likely,
      respectively, to have a relapse. Factors significantly associated with a shorter
      survival time were age > 8 years, metastatic disease at the time of initial
      diagnosis, and tumor relapse. CONCLUSIONS AND CLINICAL RELEVANCE: Results of the
      present study suggest that dogs with MCTs in the inguinal or perineal region do
      not have a worse prognosis in regard to disease-free interval or survival time
      than do dogs with MCTs in other cutaneous locations. Treatment recommendations
      for dogs with cutaneous MCTs should be based on confirmed predictors of
      biological behavior, such as histologic grade and clinical stage.

PMID- 15844432
TI  - Effect of delayed colostrum collection on colostral IgG concentration in dairy
      cows.
AB  - OBJECTIVE: To determine the effect of timing of first-milking colostrum
      collection on colostral IgG concentration. DESIGN: Prospective study. ANIMALS: 13
      healthy Holstein cows. PROCEDURES: All calvings were observed. After parturition,
      calves were not allowed to suckle and were separated from the dam. Colostrum was
      collected from a single randomly selected quarter at 2, 6, 10, and 14 hours after
      parturition until all 4 quarters were sampled. Colostral IgG concentration was
      determined via radial immunodiffusion. RESULTS: Mean colostral IgG concentration
      was 113, 94, 82, and 76 g/L at 2, 6, 10, and 14 hours after calving,
      respectively. Colostrum collected 6, 10, and 14 hours after calving had
      significantly lower IgG concentrations than did colostrum collected 2 hours after
      calving. Mean colostral IgG concentration at 14 hours after calving was
      significantly lower than that at 6 hours after calving. Cows in their third or
      greater lactation had mean colostral IgG concentrations 2 hours after calving
      (132 g/L) that were greater than the first and second lactation cows (mean, 95
      and 100 g/L, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate
      that early or immediate colostrum collection from dairy cows will maximize
      colostral IgG concentration. Adjustment of routine dairy farm management
      procedures may be required to maximize colostrum quality and minimize prevalence
      of failure of passive transfer in dairy calves.

PMID- 15844433
TI  - Effects of using retention-pond water for dust abatement on performance of
      feedlot steers and carriage of Escherichia coli O157 and Salmonella spp.
AB  - OBJECTIVE: To evaluate the effects of using retention-pond water for dust
      abatement on performance of feedlot steers and carriage of Escherichia coli O157
      and Salmonella spp. DESIGN: Matched cohort studies. ANIMALS: 2 groups of feedlot
      steers comprising 3,510 (pathogen carriage) and 3,737 (performance) animals
      housed in a large commercial feedlot in the Texas Panhandle. PROCEDURE: Steers
      were systematically allocated to treatment pens approximately 60 days after
      arrival (pathogen carriage) or at arrival (performance). For evaluation of
      pathogen carriage, feces and hide swab specimens were collected from 25 animals
      in each pen within 10 days of slaughter. Samples were submitted for bacterial
      culture for E. coli O157 and were tested with a polymerase chain reaction-based
      assay for Salmonella spp. For evaluation of performance, pen weights of animals
      were obtained at arrival and slaughter and feed delivered to each pen was
      recorded. The exposure of interest for both studies was application of retention
      pond water through fixed high-pressure sprinklers. RESULTS: Carriage of E. coli
      O157 and Salmonella spp and animal performance were not adversely affected by
      exposure to retention-pond water. Prevalences of E. coli O157 in feces, on hides,
      and either in feces or on hides for those exposed to retention-pond water were
      8.3%, 8.9%, and 15.4%, respectively; prevalences for those unexposed to retention
      pond water were 11.4%, 15.4%, and 22.6%, respectively. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that use of retention-pond water for dust abatement in
      feedlot pens does not adversely affect pathogen carriage or animal performance.

PMID- 15844434
TI  - The integration of acupuncture within medicine in the UK--the British Medical
      Acupuncture Society's 25th anniversary.
AB  - Acupuncture was first used in China, probable about 2000 years ago. When
      acupuncture first arrived in the West in the 17th century, the principles which
      the Chinese had used to explain its actions were at variance with current
      scientific knowledge of the body's structure and function. This led to the
      rejection of acupuncture by the medical profession in the UK, although individual
      practitioners adopted it with enthusiasm, usually needling the point of maximal
      tenderness to treat musculoskeletal pain. Acupuncture was more generally accepted
      in France and Germany, where the pioneering British physician Felix Mann
      encountered it in the 1950s. He then taught acupuncture to other medical
      practitioners and organised regular meetings in London, from which the British
      Medical Acupuncture Society, BMAS, emerged in 1980. The tradition of biannual
      scientific meetings has continued since then. The Society has many connections
      with prominent acupuncturists internationally and is a founder member of the
      International Council of Medical Acupuncture and Related Techniques (ICMART), and
      has hosted two world congresses. The Society was involved in standardisation of
      the meridian nomenclature published in 1990. The Society's scientific journal,
      Acupuncture in Medicine, was founded in 1981 and has gained international
      recognition, being indexed on several databases. The Society has established
      regular teaching courses at different levels, which lead to professional
      qualifications of Certificate and Diploma. The membership is now open to
      different health professionals, has grown steadily and now stands at nearly 2500.
      The Society is administered from offices in Cheshire and London. Many individual
      members have contributed to the Society's characteristic Western 'medical'
      approach to acupuncture in which needling is seen as a form of neuromuscular
      stimulation that owes little to traditional meridians or points. The Society has
      shown a particular interest in acupuncture for myofascial trigger point pain.
      Members of the Society have contributed to the evidence base of acupuncture with
      several books, clinical trials and reviews. The Society is optimistic that it
      will have an increasingly important role in promoting the use and scientific
      evaluation of acupuncture for the public benefit.

PMID- 15844435
TI  - The effects of laser acupuncture on chronic tension headache--a randomised
      controlled trial.
AB  - OBJECTIVE: Headache affects the quality of life for many people throughout the
      world. Tension headache is among the commonest forms. Acupuncture is the most
      widely practised non-medicinal treatment for headaches. The purpose of this study
      was to explore the effects of laser acupuncture in this type of headache.
      METHODS: Fifty patients with chronic tension-type headache were randomly
      allocated to treatment or placebo groups. Patients in the treatment group
      received low energy laser acupuncture to LU7, LI4, GB14, and GB20 bilaterally.
      Points were irradiated for 43 seconds, and the intensity was 1.3J (approximately
      13J/cm2). Ten sessions were given, three per week. The placebo group was treated
      in a similar way except that the output power of the equipment was set to zero.
      The outcome variables were headache intensity (VAS), duration of attacks, and
      number of days with a headache per month, by daily diary, assessed monthly to
      three months after treatment. RESULTS: There were significant differences between
      groups (P<0.001) in changes from baseline in months one, two and three, in median
      score for headache intensity (treatment group -5, -3 and -2, placebo group -1, 0
      and 0), median duration of attacks (treatment group -6, -4 and -4, placebo group 
      1, 0 and 0 hours), and median number of days with headache per month (treatment
      group -15, -10 and -8, placebo group -2, 0 and 0). CONCLUSION: This study
      suggests that laser acupuncture may be an effective treatment for chronic tension
      type headache, but the results should be confirmed in larger and more rigorous
      trials.

PMID- 15844436
TI  - Perceptions of complementary and alternative medicine amongst medical students in
      Singapore--a survey.
AB  - BACKGROUND: In view of the current upsurge of interest in, practice of, and
      research into, complementary and alternative medicine (CAM) worldwide and
      locally, a survey was conducted to gauge the understanding, interest and
      knowledge of CAM amongst medical students in a local university. METHODS: A total
      of 555 first to fifth year medical students completed a questionnaire (54%
      response rate) designed to assess their knowledge, beliefs and attitudes to CAM
      in general and 16 common CAM therapies. RESULTS: Acupuncture was the best known
      therapy, with 57% claiming to know at least something about it. No students
      claimed they knew a lot about chiropractic, osteopathy, Ayuverdic medicine,
      homeopathy and naturopathy, and many had not ever heard of these therapies.
      Knowledge of commonly held beliefs about the 16 CAM modalities was generally
      poor, even for modalities which students claimed to know most about. A
      significant number of students had knowledge about CAM that was erroneous. Lack
      of scientific support was considered to be the main barrier to implementation of
      CAM. Attitudes to CAM were positive, with 92% believing that CAM includes ideas
      and methods from which conventional medicine can benefit, 86% wishing to know
      more about CAM and 91% stating that CAM would play an important role in their
      future medical practice. CONCLUSION: As the public's use of various healing
      practices outside conventional medicine accelerates, ignorance about these
      practices by the country's future medical practitioners risks broadening the
      communication gap between the public and the profession that serves them. The
      majority of medical students recognise this risk and are keen to bridge this gap.

PMID- 15844437
TI  - Electroacupuncture direct to spinal nerves as an alternative to selective spinal
      nerve block in patients with radicular sciatica--a cohort study.
AB  - We applied electroacupuncture to the spinal nerve root by inserting needles under
      x ray imaging in three cases with radicular sciatica, as a non-pharmacological
      substitute for lumbar spinal nerve block. In all three cases, symptoms were
      markedly reduced immediately after electroacupuncture to the spinal nerve root.
      The sustained effect was noticeably longer than that of spinal nerve blocks
      previously performed, in two out of the three cases. We suggest that descending
      inhibitory control, inhibitory control at the spinal level, inhibition of
      potential activity by hyperpolarisation of nerve endings, or changes in nerve
      blood flow may be involved in the mechanism of the effect of electroacupuncture
      to the spinal nerve root. These results suggest that electroacupuncture to the
      spinal nerve root may be superior to lumbar spinal nerve block when it is applied
      appropriately in certain cases of radicular sciatica, taking into consideration
      patient age, severity of symptoms and duration of the disorder.

PMID- 15844438
TI  - The use of laser acupuncture for the treatment of neurogenic pruritus in a child-
      a case history.
AB  - This report describes the successful treatment using laser acupuncture of a six
      year old girl with neurogenic pruritus of the abdomen. It is the first case
      report of neurogenic pruritus treated by laser acupuncture. The main advantage of
      using low energy laser, as opposed to acupuncture needles, to stimulate points,
      is that low energy laser causes little or no sensation, which is particularly
      useful when treating children.

PMID- 15844439
TI  - A case report of postulated 'Barre Lieou syndrome'.
AB  - The case history presented is of a 32 year old woman suffering with severe
      occipital and bilateral temporal pain together with autonomic disturbances
      affecting her vision, balance and breathing, symptoms which have been postulated
      as 'Barre Lieou syndrome'. She complained of pain referred to the left arm and
      associated circulatory and sensory disturbance in keeping with the diagnosis of
      complex regional pain syndrome type I. Traditional Chinese and Western trigger
      point acupuncture techniques were used in order to treat her pain and autonomic
      dysfunction. Acupuncture was successful in reducing, but not totally alleviating,
      her pain, and was particularly effective in reducing the majority of autonomic
      symptoms.

PMID- 15844440
TI  - In silico modelling of ADMET-a minireview of work from 2000 to 2004.
AB  - This article represents a minireview of work published so far in the 21st century
      in the in silico ADMET field of research related to investigations in the areas
      of solubility, hERG and cytochrome P450 3A4. Various approaches including 2D- and
      3D-QSARs and pharmacophore modelling are discussed. The pros and cons of the
      methods used and models derived are examined. More general remarks on model
      development and validation are also reported.

PMID- 15844441
TI  - QSAR modeling based on structure-information for properties of interest in human
      health.
AB  - The development of QSAR models based on topological structure description is
      presented for problems in human health. These models are based on the structure
      information approach to quantitative biological modeling and prediction, in
      contrast to the mechanism-based approach. The structure-information approach is
      outlined, starting with basic structure information developed from the chemical
      graph (connection table). Information explicit in the connection table (element
      identity and skeletal connections) leads to significant (implicit) structure
      information that is useful for establishing sound models of a wide range of
      properties of interest in drug design. Valence state definition leads to
      relationships for valence state electronegativity and atom/group molar volume.
      Based on these important aspects of molecules, together with skeletal branching
      patterns, both the electrotopological state (E-state) and molecular connectivity
      (chi indices) structure descriptors are developed and described. A summary of
      four QSAR models indicates the wide range of applicability of these structure
      descriptors and the predictive quality of QSAR models based on them: aqueous
      solubility (5535 chemically diverse compounds, 938 in external validation),
      percent oral absorption (%OA, 417 therapeutic drugs, 195 drugs in external
      validation testing), AMES mutagenicity (2963 compounds including 290 therapeutic
      drugs, 400 in external validation), fish toxicity (92 substituted phenols,
      anilines and substituted aromatics). These models are established independent of
      explicit three-dimensional (3-D) structure information and are directly
      interpretable in terms of the implicit structure information useful to the drug
      design process.

PMID- 15844442
TI  - Structure-based methods for the prediction of the dominant P450 enzyme in human
      drug biotransformation: consideration of CYP3A4, CYP2C9, CYP2D6.
AB  - Metabolic drug-drug interactions are receiving more and more attention from the
      in silico community. Early prediction of such interactions would not only improve
      drug safety but also contribute to make drug design more predictable and
      rational. The aim of this study was to build a simple and interpretable model for
      the determination of the P450 enzyme predominantly responsible for a drug's
      metabolism. The P450 enzymes taken into consideration were CYP3A4, CYP2D6 and
      CYP2C9. Physico-chemical descriptors and structural descriptors for 96 currently
      marketed drugs were submitted to statistical analysis using the formal inference
      based recursive modelling (FIRM) method, a form of recursive partitioning.
      Generally accepted knowledge on metabolism by these enzymes was also used to
      construct a hierarchical decision tree. Robust methods of variable selection
      using recursive partitioning were utilised. The descriptive ability of the
      resulting hierarchical model is very satisfactory, with 94% of the compounds
      correctly classified.

PMID- 15844443
TI  - A spreadsheet program for modeling quantitative structure-pharmacokinetic
      relationships for inhaled volatile organics in humans.
AB  - The extent and profile of target tissue exposure to toxicants depend upon the
      pharmacokinetic processes, namely, absorption, distribution, metabolism and
      excretion. The present study developed a spreadsheet program to simulate the
      pharmacokinetics of inhaled volatile organic chemicals (VOCs) in humans based on
      information from molecular structure. The approach involved the construction of a
      human physiologically-based pharmacokinetic (PBPK) model, and the estimation of
      its parameters based on quantitative structure-property relationships (QSPRs) in
      an Excel spreadsheet. The compartments of the PBPK model consisted of liver,
      adipose tissue, poorly perfused tissues and richly perfused tissues connected by
      circulating blood. The parameters required were: human physiological parameters
      such as cardiac output, breathing rate, tissue volumes and tissue blood flow
      rates (obtained from the biomedical literature), tissue/air partition
      coefficients (obtained using QSPRs developed with rat data), blood/air partition
      coefficients (Pb) and hepatic clearance (CL). Using literature data on human Pb
      and CL for several VOCs (alkanes, alkenes, haloalkanes and aromatic
      hydrocarbons), multi-linear additive QSPR models were developed. The numerical
      contributions to human Pb and CL were obtained for eleven structural fragments
      (CH3, CH2, CH, C, C [double bond] C, H, Cl, Br, F, benzene ring, and H in the
      benzene ring structure). Using these data as input, the PBPK model written in an
      Excel spreadsheet simulated the inhalation pharmacokinetics of ethylbenzene (33
      ppm, 7 h) and dichloromethane (100 ppm, 6 h) in humans exposed to these
      chemicals. The QSPRs developed in this study should be useful for predicting the
      inhalation pharmacokinetics of VOCs in humans, prior to testing and
      experimentation.

PMID- 15844444
TI  - 3D QSAR investigation of the blood-brain barrier penetration of chemical
      compounds.
AB  - In the present study, we investigated structure-permeability relationships for
      the blood-brain barrier (BBB) of 16 imipramine and phenothiazine derivatives. The
      compounds belong to structurally related chemical classes of catamphiphiles,
      representatives of which have previously been investigated for membrane activity
      and ability to overcome multidrug resistance (MDR) in tumour cells. These studies
      show that phenothiazines and structurally related drugs (imipramines,
      thioxanthenes, acridines) interact with membrane phospholipids, and additionally
      inhibit the MDR transport P-glycoprotein. This study aimed to identify common 3D
      structural characteristics of these compounds related to their mechanism of
      transport across the BBB. For this purpose Genetic Algorithm Similarity Programme
      (GASP), Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular
      Similarity Index Analysis (CoMSIA) were applied. The results demonstrate the
      importance of the spatial distribution of molecular hydrophobicity for the BBB
      penetration of the investigated compounds. It suggests that the compounds should
      follow a specific profile of two hydrophobic and one hydrophilic centres in a
      particular space configuration, for optimal BBB penetration.

PMID- 15844445
TI  - QSAR modeling of datasets with enantioselective compounds using chirality
      sensitive molecular descriptors.
AB  - Shape descriptors used in 3D QSAR studies naturally take into account chirality;
      however, for flexible and structurally diverse molecules such studies require
      extensive conformational searching and alignment. QSAR modeling studies of two
      datasets of fragrance compounds with complex stereochemistry using simple
      alignment-free chirality sensitive descriptors developed in our laboratories are
      presented. In the first investigation, 44 alpha-campholenic derivatives with
      sandalwood odor were represented as derivatives of several common structural
      templates with substituents numbered according to their relative spatial
      positions in the molecules. Both molecular and substituent descriptors were used
      as independent variables in MLR calculations, and the best model was
      characterized by the training set q2 of 0.79 and external test set r2 of 0.95. In
      the second study, several types of chirality descriptors were employed in
      combinatorial QSAR modeling of 98 ambergris fragrance compounds. Among 28
      possible combinations of seven types of descriptors and four statistical modeling
      techniques, k nearest neighbor classification with CoMFA descriptors was
      initially found to generate the best models with the internal and external
      accuracies of 76 and 89%, respectively. The same dataset was then studied using
      novel atom pair chirality descriptors (cAP). The cAP are based on a modified
      definition of the atomic chirality, in which the seniority of the substituents is
      defined by their relative partial charge values: higher values correspond to
      higher seniorities. The resulting models were found to have higher predictive
      power than those developed with CoMFA descriptors; the best model was
      characterized by the internal and external accuracies of 82 and 94%,
      respectively. The success of modeling studies using simple alignment free
      chirality descriptors discussed in this paper suggests that they should be
      applied broadly to QSAR studies of many datasets when compound stereochemistry
      plays an important role in defining their activity.

PMID- 15844446
TI  - POPs: a QSAR system for developing categories for persistent, bioaccumulative and
      toxic chemicals and their metabolites.
AB  - This paper presents the framework of a QSAR-based decision support system which
      provides a rapid screening of potential hazards, classification of chemicals with
      respect to risk management thresholds, and estimation of missing data for the
      early stages of risk assessment. At the simplest level, the framework is designed
      to rank hundreds of chemicals according to their profile of persistence,
      bioaccumulation potential and toxicity often called the persistent organic
      pollutant (POP) profile or the PBT (persistent bioaccumulative toxicant) profile.
      The only input data are the chemical structure. The POPs framework enables
      decision makers to introduce the risk management thresholds used in the
      classification of chemicals under various authorities. Finally, the POPs
      framework advances hazard identification by integrating a metabolic simulator
      that generates metabolic map for each parent chemical. Both the parent chemicals
      and plausible metabolites are systematically evaluated for metabolic activation
      and POPs profile.

PMID- 15844447
TI  - External validation of EPIWIN biodegradation models.
AB  - The BIOWIN biodegradation models were evaluated for their suitability for
      regulatory purposes. BIOWIN includes the linear and non-linear BIODEG and MITI
      models for estimating the probability of rapid aerobic biodegradation and an
      expert survey model for primary and ultimate biodegradation estimation.
      Experimental biodegradation data for 110 newly notified substances were compared
      with the estimations of the different models. The models were applied separately
      and in combinations to determine which model(s) showed the best performance. The
      results of this study were compared with the results of other validation studies
      and other biodegradation models. The BIOWIN models predict not-readily
      biodegradable substances with high accuracy in contrast to ready
      biodegradability. In view of the high environmental concern of persistent
      chemicals and in view of the large number of not-readily biodegradable chemicals
      compared to the readily ones, a model is preferred that gives a minimum of false
      positives without a corresponding high percentage false negatives. A combination
      of the BIOWIN models (BIOWIN2 or BIOWIN6) showed the highest predictive value for
      not-readily biodegradability. However, the highest score for overall predictivity
      with lowest percentage false predictions was achieved by applying BIOWIN3 (pass
      level 2.75) and BIOWIN6.

PMID- 15844448
TI  - In silico prediction of receptor-mediated environmental toxic phenomena
      application to endocrine disruption.
AB  - It is an objective of our institution to establish a virtual laboratory allowing
      for a reliable in silico estimation of the harmful effects triggered by drugs,
      chemicals and their metabolites. In the recent past, we have developed the
      underlying technology (Multi-dimensional QSAR: Quasar and Raptor) and compiled a
      pilot system including the 3D models of three receptors known to mediate
      endocrine-disrupting effects (the aryl hydrocarbon receptor, the estrogen
      receptor and the androgen receptor, respectively) and validated them against 310
      compounds (drugs, chemicals, toxins). Within this set up we could demonstrate
      that our concepts are able to both recognize toxic compounds substantially
      different from those used in the training set as well as to classify harmless
      compounds clearly as being non-toxic. This suggests that our approach can be used
      for the prediction of adverse effects of drug molecules and chemicals.

PMID- 15844449
TI  - The impact of variable selection on the modelling of oestrogenicity.
AB  - Many oestrogenic chemicals exert their activity via specific interactions with
      the oestrogen receptor (ER). The objective of the present study was to identify
      significant descriptors associated with the ER binding affinities of a large and
      diverse set of compounds to drive quantitative structure-activity relationships
      (QSARs). To this end, a variety of statistical methods were employed for variable
      selection. These included stepwise regression and partial least squares (PLS)
      analyses, as well as a non-linear recursive partitioning method (Formal Inference
      based Recursive Modelling). A total of 157 molecular descriptors including
      quantum mechanical, graph theoretical, indicator variables and log P were used in
      the study. Furthermore, cluster analysis of variables was performed to identify
      groups of descriptors representing similar molecular features. Hierarchical PLS
      analyses were performed, where the scores of the significant components of either
      PLS or principle component analysis (PCA), performed separately on each cluster,
      were used as the variables for the top model. This reduced the number of the
      variables representing the larger clusters, leading to a similar number of
      descriptors for each distinct molecular feature. The results showed that the most
      important molecular properties for stronger ER binding affinity are molecular
      size and shape, the presence of a phenol moiety as well as other aromatic groups,
      hydrophobicity and presence of double bonds. The best PLS model obtained, in
      terms of predictive ability, was a hierarchical PLS model. However, a rigorous
      validation study showed that the MLR model using descriptors selected by stepwise
      regression has greater predictive power than the PLS models.

PMID- 15844450
TI  - QSPR analysis of the partitioning of vaporous chemicals in a water-gas phase
      system and the water solubility of liquid and solid chemicals on the basis of
      fragment and physicochemical similarity and hybot descriptors.
AB  - QSPR analyses of the solubility in water of 558 vapors, 786 liquids and 2045
      solid organic neutral chemicals and drugs are presented. Simultaneous
      consideration of H-bond acceptor and donor factors leads to a good description of
      the solubility of vapors and liquids. A volume-related term was found to have an
      essential negative contribution to the solubility of liquids. Consideration of
      polarizability, H-bond acceptor and donor factors and indicators for a few
      functional groups, as well as the experimental solubility values of structurally
      nearest neighbors yielded good correlations for liquids. The application of
      Yalkowsky's "General Solubility Equation" to 1063 solid chemicals and drugs
      resulted in a correlation of experimental vs calculated log S values with only
      modest statistical criteria. Two approaches to derive predictive models for
      solubility of solid chemicals and drugs were tested. The first approach was based
      on the QSPR for liquids together with indicator variables for different
      functional groups. Furthermore, a calculation of enthalpies for intermolecular
      complexes in crystal lattices, based on new H-bond potentials, was carried out
      for the better consideration of essential solubility- decreasing effects in the
      solid state, as compared with the liquid state. The second approach was based on
      a combination of similarity considerations and traditional QSPR. Both approaches
      lead to high quality predictions with average absolute errors on the level of
      experimental log S determination.

PMID- 15844451
TI  - [Tsunami--the death waves].
AB  - On December 26, 2004, the fourth strongest earthquake over the past century
      struck in the Indian Ocean off the western coast of northern Sumatra, Indonesia.
      Measuring 9.0 in magnitude, the earthquake triggered massive tsunamis that struck
      the Indian Ocean countries and Somalia, and killed more than tens of thousands
      and destroyed entire villages, leaving over a million homeless. Tsunamis are
      water waves that are caused by sudden vertical movement of a large area of the
      sea floor during an undersea earthquake. Tsunami speed can exceed 800 kilometers
      per hour, and as it reaches shallow water the height of the wave drastically
      increases. There are two natural warning signs of a possible tsunami: the
      earthquake itself and later, in the minutes preceding a tsunami strike, the sea
      often recedes temporarily from the coast. Despite these warning signs and despite
      a lag of up to several hours between the earthquake and the impact of the
      tsunamis, nearly all of the victims were taken completely by surprise. One of the
      most common myths associated with natural disasters is that dead bodies are
      responsible for the spread of epidemics. This article discusses the myths that
      often lead authorities and others to take inappropriate action, and presents
      valuable lessons to be learned from this catastrophic disaster.

PMID- 15844452
TI  - [The aftermath of the Tsunami].

PMID- 15844453
TI  - [Opsoclonus myoclonus with ataxia].
AB  - Opsoclonus myoclonus with ataxia (OMA) is a rare neurological disorder. The
      syndrome is characterized by involuntary, conjugate, multidirectional eye
      movements accompanied by involuntary movements of limb or face, and sometimes
      ataxia, dysarthria, irritability, dementia, altered level of consciousness and
      even death. OMA is associated with various etiologies including infectious,
      toxic, drug-related, vascular and paraneoplastic conditions. Paraneoplastic
      opsoclonus myoclonus with ataxia (POMA) is more common in patients over 40 years
      of age and is usually associated with lung (especially small cell), breast and
      ovarian cancer but has also been reported with many other cancers. The syndrome
      is thought to be mediated by autoantibodies directed against onconeural antigens
      that are expressed by the tumor as well as by neurons. Studies from several
      laboratories were able to demonstrate a role for the cellular response in the
      pathogenesis of POMA. The results for treatment of this syndrome have been
      disappointing, although aggressive multimodality immunosuppressive treatments
      have been used. This is a case study of a patient with POMA who clearly
      demonstrates the difficulties in the diagnosis and treatment of this syndrome.

PMID- 15844454
TI  - [Combined radioiodine (I131) treatment and radio-guided surgery for recurrent
      cervical well-differentiated thyroid cancer].
AB  - Local recurrence and cervical lymph node involvement are relatively common in
      patients with well-differentiated thyroid carcinoma. Since these patients are
      young and have a good prognosis, their treatment is challenging. Therapeutic
      doses of radioiodine (I131) are seldom curative and include a long period of
      discomfort--stopping the replacement therapy. Most patients will require surgery
      to eradicate the recurrent disease. However, when performed, excision of all
      involved tissue should be complete and accomplished in a single procedure since
      repeated cervical surgery is technically difficult, carries a high morbidity rate
      and yields bad cosmetic results. This study aims to combine radioiodine (I131)
      treatment and radio-guided surgery to improve the completeness of surgical
      excision without wide resections of cervical tissues. The combined treatment
      protocol was described previously and includes preparation of the patient for
      radioiodine (I131) treatment, administration of a therapeutic dose of 3.7 GBq of
      radioiodine (I131) in the hypothyroid state and using the radio-activity as a
      marker for identifying tumor aggregates intraoperatively using a hand held gamma
      probe. Both patients treated show complete removal of all neoplastic foci with
      radioiodine uptake. Moreover, in both patients the intraoperative probe
      identified additional metastatic foci that were not shown by the preoperative
      scan. Although our experience is limited (only two patients), and a larger series
      with a longer follow-up period is needed, we believe radio-guided surgery for
      recurrent or persistent cervical well-differentiated thyroid cancer offers an
      important therapeutic tool.

PMID- 15844455
TI  - [Towards the inclusion of health state in the Israeli risk-adjustment scheme
      using medical diagnoses--some intermediate results].
AB  - BACKGROUND: A proper risk-adjustment mechanism in the allocation of funds to the
      health funds is a key element in the efficiency and equity of the health system.
      Since 1995, the Israeli risk-adjustment is based only on age, while, in many
      similar systems, considerable effort has been made to include health state as a
      risk-adjuster. OBJECTIVES: This study aims to suggest a risk-adjusted capitation
      scheme based on inpatient diagnoses. METHODS: Using the DxCG software and the
      MOH's hospitalization database for the period 1994-1997, the authors built a
      preliminary model to predict inpatient costs at a given year, based on diagnoses,
      age and sex in previous-year hospitalizations. The second stage, in which total
      health care costs are predicted based on the same previous-year information, has
      not been realized because of lack of cooperation from the health funds. RESULTS:
      The use of the DxCG diagnoses model with the Israeli data is feasible. However,
      further research is needed to construct the best Israeli model. The prediction of
      inpatient cost according to the diagnoses model is superior to that obtained by
      the demographic model.

PMID- 15844456
TI  - [Pulsed radiofrequency treatment of severe radicular pain].
AB  - Radiofrequency (RF) lesions have been used for over 25 years in the treatment of
      intractable pain of spinal origin. The conventional idea is that the heat
      generated in the tissue surrounding the electrode tip leads to destruction of
      nerve fibers. In case of mechanical back pain, an electrode positioned adjacent
      to the medial branch of the dorsal root may reduce the input of noxious nerve
      stimuli and alleviate pain. For treatment of patients with severe radicular pain
      the authors often apply pulsed radiofrequency current. This technique enables the
      application of a relatively high voltage near the dorsal root ganglion, avoiding
      the deleterious thermal effect of the current. It was found to exert a beneficial
      effect in cases of intractable radicular pain. This study reports the result of
      pulsed RF in 28 patients suffering from severe radicular pain treated by pulsed
      radiofrequency current with follow-up at periods of 3, 6 and 12 months after
      treatment. There were 20 cases of low back pain and 8 with neck pain, with an
      average age of 56.7 years. The first follow-up after 3 months revealed the
      following results: excellent results in 2 cases (7.1%), good results in 12 cases
      (42/9%), fair in 9 (32/1%) and 5 (17/9%) reported that their condition have not
      changed. Results after 6 and 12 months were excellent in 2 (both groups), good in
      7 and 6 respectively, 11 fair (both groups) and unresponsiveness to treatment was
      noticed in 8 patients after 6 and 9 after 12 months. Significant reduction was
      found in the Visual Analog Scale for pain from an average of 8.8 to 4.2 after 3
      months, 4.8 after 6 months and 4.9 after 1 year. CONCLUSION: Pulsed RF treatment
      is a safe and simple procedure to control radicular pain in the cervical and
      lumbar regions. Following the current study the authors stress the need for
      further prospective, double-blind studies for better investigation of this
      technique.

PMID- 15844457
TI  - [Reported practices of antimicrobial use for upper respiratory tract infections].
AB  - AIM: To determine the reported antibiotic prescribing practices for upper
      respiratory tract infections in children among pediatricians and family
      physicians. METHODS: Regional survey of practicing pediatricians and family
      physicians and comparison of the survey responses of 81 physicians with the
      recently published recommendations of the Centers for Disease Control and
      Prevention. RESULTS: Whereas almost all the physicians agreed that a diagnosis of
      acute otitis media required documentation of middle ear effusion and acute
      illness, 28% of family physicians and 12% of pediatricians reported that they
      routinely prescribed antibiotics for children with bronchitis, even though this
      is not recommended. In this survey 39% of pediatricians and 47% of family
      physicians reported that they omitted laboratory testing for the diagnosis of
      group A streptococcal pharyngitis, and of those who submitted samples for
      testing, most reported that they prescribed antibiotics immediately without
      waiting for the results. Even though these recommendations state that sinus
      tenderness is rare in young children with sinusitis, more than 48% of the
      physicians believed that both this and the presence of purulent rhinitis were
      essential to confirm this diagnosis. While none of the pediatricians reported
      prescribing antibiotics for the common cold, 17% of the family physicians did so
      (p = 0.006). CONCLUSIONS: The reported prescribing practices of the physicians in
      this survey are not in line with the recommendations. Effective intervention is
      needed to encourage the judicious use of antibiotics in Israel.

PMID- 15844458
TI  - [Outbreaks of norovirus gastroenteritis in nursing homes in Haifa, 2002-2003].
AB  - BACKGROUND: The incidence rate of Norovirus gastroenteritis is unknown since
      diagnostic tests are less readily available than for other agents. This pathogen
      is identified in less than 10% of acute gastrointestinal illness, despite the
      fact that recent reports from the United States attribute more than 50% of
      outbreaks to Noroviruses. OBJECTIVES: This article describes three outbreaks of
      gastroenteritis caused by Noroviruses in three of Haifa's chronic care hospitals
      in order to raise awareness of its main role as a common agent in such outbreaks,
      and thereby include it in the differential diagnosis of outbreak investigations.
      METHODS: Methods employed included epidemiological investigation of the
      outbreaks, sanitary inspection, personal interviews of hospital staff members,
      data collection from medical files and laboratory diagnosis by electron
      microscopy and RT-PCR of stool and vomitus for Noroviruses. RESULTS: Noroviruses
      were identified in faeces and vomitus of patients in 2 outbreaks in chronic care
      hospitals in Haifa. Attack rates were high (20-41%). Proximity in time to these 2
      outbreaks, and clinical and epidemiological findings lead us to attribute another
      outbreak in a third hospital to norovirus as well. CONCLUSIONS: Physicians in
      institutions and the community should include Noroviruses in the differential
      diagnosis of outbreaks of gastroenteritis, particularly in cases where no other
      pathogens have been isolated. Timely requests for identification of Noroviruses
      are essential. The institution of good hygienic practices is important to prevent
      spread of this highly infectious agent.

PMID- 15844459
TI  - [Ischemic heart disease risk factor among women].
AB  - In recent years the medical literature has been dealing with coronary heart
      disease among women and the association with coronary heart disease risk factors.
      This article reviews the latest medical publications on these risk factors and
      their association with heart disease among women.

PMID- 15844460
TI  - [Heart disease in women: different but similar].
AB  - Atherosclerotic cardiovascular disease is the leading cause of mortality among
      women in the western hemisphere. Until recently, cardiovascular disease was
      considered a disease mainly affecting men, and information regarding the unique
      characteristics of cardiovascular disease in women was lacking. Recent research
      has demonstrated the differences between the genders regarding risk factors, the
      presentation of coronary events and the response to various therapeutic
      modalities. Despite these differences, it is clear that women benefit from risk
      reduction strategies similar to those effectively implemented in men. More
      research is needed to further clarify the differences between the genders.

PMID- 15844461
TI  - [Measurement and assessment of habitual physical activity in epidemiological
      studies].
AB  - Epidemiological study and laboratory evidence show that physical activity
      protects against the development and progression of chronic diseases. The
      physiological and biomechanical principles of the assessment of physical activity
      are ambiguous, energy expenditure calculations are complex, and numerous
      difficulties can be encountered in developing simple field techniques for
      assessing habitual activity. The greatest obstacle to validating field methods of
      assessing habitual physical activity or energy expenditure in humans has been the
      lack of adequate comparison criteria for the technique. Physical activity can be
      described as having four dimensions: duration (minutes/hours), frequency (time
      per week/per month), intensity (rate of energy expenditure) and circumstances or
      purpose of the activity. Methodology incorporating questionnaires/interviews are
      relatively inexpensive, and at present are the only methods feasible for large
      population studies. Specific activities can be identified in conjunction with
      frequency and duration. The procedure does not influence subjects' activities to
      the extent that can occur with observation or diary keeping. The limitations of
      questionnaires/interviews are the actual definitions and interpretations of the
      term "physical activity", despite the attempts of interviewers to provide a clear
      definition. Subjects do not necessarily recall their activities accurately; they
      may tend to overestimate time or intensity. A self-administered questionnaire
      must be suited to respondents' ages and education levels. Detailed
      questionnaires/interviews place a considerable burden on subjects.

PMID- 15844462
TI  - [Pulmonary hypertension--classification and treatment: new guidelines].
AB  - Pulmonary arterial hypertension is a severe pulmonary vascular disease
      characterized by elevated pulmonary vascular resistance and low cardiac output.
      Prior to prostacyclin therapy, it was a fatal disease with a median survival of 3
      years. In recent years, the understanding and treatment of the disease have
      significantly improved patient outcome. The new therapeutic guidelines are based
      on the finding that vasoconstriction and vascular remodeling correlated with
      endothelial dysfunction, endothelin overexpression and diminished prostacyclin
      and nitric oxide synthesis. This article outlines the new classification and the
      current therapeutic guidelines accepted in the world presenting the role of
      prostacyclins, endothelin antagonist, phosphodiesterase V inhibitor, and the
      potential value of combination therapies.

PMID- 15844463
TI  - [Imaging of acute cervical spine trauma].
AB  - The cervical spine is injured in 2-3% of major trauma patients. Over the past 15
      years there have been dramatic changes in the approach to imaging acute cervical
      spine trauma. Radiographic clearance for injury must be provided efficiently and
      accurately. There are numerous choices for clearance that are now in clinical
      practice: plain radiographs, computed tomography (CT) with multiplanar
      reformations, and magnetic resonance imaging (MRI). This article reviews the
      literature on methods of C-spine clearance and emphasizes the pitfalls of each
      modality. The issue of clinical versus radiographic evaluation of low risk
      patient is also discussed. An algorithm for the use of advanced imaging in acute
      trauma situation is proposed.

PMID- 15844464
TI  - [Mary Mallon, Mr. N and Mr. Koch as well].
AB  - Societal attitudes towards disease carriers is not ideal and is often associated
      with prejudice. This phenomenon was well documented in the era of Robert Koch who
      was one of the leading scientists claiming that disease carriers might cause
      epidemics. The authors recount the tale of two salmonella typhi carriers, Mr. N
      and Mary Mallon, who were responsible for transmitting typhoid. These cases
      highlight the problematic nature of the subject and the need for an enhanced
      medical and legal-social treatment model aimed at improving the status of disease
      carriers and limiting their impact on society.

PMID- 15844465
TI  - [Red herring].

PMID- 15844466
TI  - Physiological and pathological growth hormone secretion.
AB  - Growth hormone (GH) secretion is normally episodic, with discrete bursts of GH
      super-imposed on a minimal basal level of production. This pattern of GH
      production yields a dynamic state between a low baseline and intervening peaks,
      posing a challenge for the clinician attempting to understand the 'true GH
      status' in a specific patient. This pulsatile pattern is maintained throughout
      the day, but there are clear differences between different segments of the day,
      with approximately two-thirds of the total daily secretion produced at night. The
      dynamic nature of GH production has led many investigators to suggest that when
      evaluating short stature, parameters of spontaneous GH production be applied
      rather than the GH response to artificial stimulation. GH secretory patterns in
      healthy control populations are compared to those in patients with several
      conditions seen by the pediatric endocrinologist (classical GH deficiency, GH
      neurosecretory dysfunction, acute lymphoblastic leukemia, hypothyroidism, small
      for gestational age, Russell-Silver syndrome, constitutional delay of growth and
      puberty and Fanconi's anemia) and variables used for analysis of these patterns
      are described. Inferences made from comprehensive evaluations of the GH axis in
      Fanconi's anemia provide unique insight into general GH pathophysiology.

PMID- 15844467
TI  - Choice of gender in 5alpha-reductase deficiency: a moving target.
AB  - Steroid 5alpha-reductase deficiency is a rare, male-limited autosomal recessive
      disorder caused by mutation in the SRD5A2 gene resulting in a deficiency of
      dihydrotestosterone (DHT) during fetal development. Here we report an affected
      46,XY adolescent who was born with incompletely virilized genitalia and was
      raised in the female gender. At 12 years of age, the patient requested feminizing
      genital surgery. Surgery was withheld and psychiatric counseling was instituted.
      At 14 years of age, the patient's gender identity and role appeared to be in
      transition from a female to an increasingly male gender. This case demonstrates
      that in patients with disorders such as 5alpha-reductase deficiency, in which
      significant prenatal androgen exposures are combined with postnatal virilization,
      adult gender identity and gender role may be a dynamic process that is not
      complete until well after adolescence.

PMID- 15844468
TI  - Adrenocortical carcinoma: prognostic indices based on clinical and
      immunohistochemical markers.
AB  - Adrenocortical carcinoma is a rare condition with an unpredictable prognosis as a
      rule. The authors retrospectively analyzed the clinical outcome of 46 patients
      (31 F, 15 M) during 16 years building up a numerical index for the prognosis,
      based on clinical and immunohistochemical data. Four indices were analyzed: J1=
      (Y + 2L + 4H)/T; J2 = (J1) square root of W/200; J3 = (O + Y + 2L + 4H)/T; J4 =
      (J3) square root W/200. Y = 1 when chronological age (CA) >33 mo, Y = 0 when CA <
      or =33 mo; L = 1 for right sided tumor and L = 0 for left sided tumor; H = 1 in
      presence of hypertension and H = 0 for normal blood pressure; T = length of
      disease in months; W = weight of tumor (g); O = 1 in the absence of p53 protein
      and O = 0 in the presence of p53. The chance of bad prognosis was observed when
      age is >33 mo, tumor is on the right side, systemic hypertension is present,
      tumor weight >250 g, in the absence of p53, J1, J2, J3 >0.4 (p <0.001) and J4
      >0.5 (p <0.01). Clinical data and the mathematical model enabled us to establish
      probabilities of good prognosis in 78-96% and bad prognosis in 63-83%.

PMID- 15844469
TI  - Androgen replacement in adolescents and young women with hypopituitarism.
AB  - The aim of this study was to test the hypothesis that young women with androgen
      deficiency due to hypopituitarism would benefit from androgen replacement in the
      form of dehydroepiandrosterone (DHEA). Five young women, age 15.2-23.1 years,
      with panhypopituitarism were studied in a 12-month double blind placebo
      controlled crossover trial of DHEA replacement in a dose 50 mg/day (Belmar
      Pharmacy, Lakewood, CO). All had growth hormone (GH), thyroid stimulating hormone
      (TSH), adrenocorticotropic hormone (ACTH) and antidiuretic hormone deficiencies.
      Gonadotropin deficiency was complete in three and partial in two. The patients
      were evaluated at baseline, 6 months and 12 months. Serum hormone levels, body
      composition, lumbar bone mineral density (BMD), exercise capacity and tests of
      psychological function were performed. DHEA replacement restored serum DHEA
      levels to normal, 359.8+/-337 ng/dl (12.5+/-11.7 nmol/l). The Life Situation
      Survey showed significantly better life satisfaction on DHEA than placebo (110 vs
      102, p = 0.05). Trends for improved maximal oxygen uptake (VO2), and decreased
      percent body fat did not reach statistical significance. In conclusion, androgen
      replacement with DHEA should be considered in young women with
      panhypopituitarism. Further studies over longer periods in larger groups of
      patients are necessary to better evaluate the effects of DHEA replacement on BMD,
      muscle strength and body composition.

PMID- 15844470
TI  - Activity of the growth hormone/insulin-like growth factor-I axis in critically
      ill children.
AB  - Critical illness has an important impact on the human endocrine system. Very few
      studies have been performed to elucidate the alterations of the GH/IGF-I axis in
      acutely ill children. The aim of this study was to investigate several parameters
      of this axis in children with trauma (TRA) and sepsis (SEP) requiring admission
      to the pediatric intensive care unit (PICU). A total of 16 children, ten with TRA
      and six with SEP (age 1-10 years) as well as 18 healthy children (CS) of similar
      age and gender were included in the study. Two children, one with TRA and one
      with SEP, died. Serum IGF-I and -II, IGFBP-1 and -3, and GH levels were measured
      on days 1, 3 and 7 after admission. GH levels were higher in the patients than in
      CS (p = 0.04), with no difference between TRA and SEP, and were elevated during
      PICU stay (p = 0.05). Serum IGF-I, -II and IGFBP-3 were lower in the patients
      than in CS (p = 0.03, 0.02 and 0.001, respectively) with a tendency to increase
      up to day 7. Finally, IGFBP-1 levels were similar in the patients and CS. These
      findings indicate that critically ill children are characterized by low levels of
      IGF-I and -II as well as IGFBP-3 accompanied by elevated levels of GH, probably
      reflecting the development of peripheral GH resistance. No significant
      differences were found between the different catabolic conditions, sepsis and
      trauma.

PMID- 15844471
TI  - Efficacy of congenital hypothyroidism neonatal screening in preterms less than 32
      weeks of gestational age: more evidence.
AB  - OBJECTIVE: To evaluate the double screening performed for congenital
      hypothyroidism (CH) to preterm infants <32 weeks of gestational age (GA) between
      1994 and 2003. INFANTS AND METHODS: TSH was assessed by IFMA. Infants were
      classified as: term (T) (>37 weeks GA); preterm (PT) (33-37 weeks GA); and very
      preterm (VPT) (< or =32 weeks GA). RESULTS: In 585,221 screened infants, CH was
      confirmed in 228 T, 23 PT and seven VPT. An increasing incidence of CH was found
      with decreasing GA, affecting 1:1,603 PT and 1:585 VPT. PT infants had 1.5 times
      more risk than full-term infants of suffering CH, and VPT 4 times more. Only 4/7
      affected VPT had an adequate double screening as requested. Three had elevated
      TSH values in the first sample and in one a normal TSH (10.3 mIU/l) at 3 days
      rose to 240 mIU/l after day 15. In the remaining three VPT, TSH in the unique
      filter paper sample (21 to 34 days) was markedly elevated. CONCLUSIONS: Our
      findings reinforce the need for awareness in neonatal settings for adequate
      screening of VPT infants. Screening in the first week of life was effective in
      detection of most but not all affected VPT. Larger studies are needed in order to
      establish accurate screening recommendations for VPT newborns. Until this step is
      reached, repeated screening is advised in these infants.

PMID- 15844472
TI  - Active and total ghrelin concentrations in the newborn.
AB  - BACKGROUND: Ghrelin is a peptide with a potent capacity to release GH and other
      metabolic activities. An acyl modification is indispensable for biological
      activity. Acylated and desacylated forms of ghrelin are both present in the
      blood. No data exist about the ratio between active ghrelin and total ghrelin in
      the first period of life. OBJECTIVE: To investigate whether ghrelin may be
      involved in physiological roles during fetal life. INFANTS AND METHODS: Ghrelin,
      growth hormone (GH), and leptin concentrations were measured in cord plasma in 98
      newborns of healthy mothers. Acyl-ghrelin and the sum of acylated and desacylated
      forms of ghrelin (total ghrelin) were measured using specific radioimmunoassays.
      RESULTS: Acylated ghrelin and total ghrelin did not correlate with birth weight,
      gestational age, body mass index, head circumference, birth length, leptin or GH
      in plasma cord blood. CONCLUSIONS: The absence of clinically significant
      correlations between both active and total ghrelin and GH, leptin or
      anthropometric data does not enable us to ascribe a precise role to ghrelin in
      prenatal life.

PMID- 15844473
TI  - Three novel mutations in POU1F1 in Israeli patients with combined pituitary
      hormone deficiency.
AB  - BACKGROUND: POU1F1, a pituitary-specific transcription factor of the class 1 POU
      family, is crucial for the development and differentiation of the anterior
      pituitary gland. Mutations in the POU1F1 gene have been shown to be responsible
      for a syndrome of combined pituitary hormone deficiency (CPHD), including
      prolactin, growth hormone and thyroid-stimulating hormone deficiencies. METHODS:
      Five patients with CPHD from three families were evaluated. The clinical and
      biochemical data were taken from the medical records. DNA was analyzed by
      polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE),
      and sequencing. RESULTS: Molecular analysis yielded three novel mutations in
      POU1F1: W193X, Q242R (-2 bp), and F262L. CONCLUSIONS: Three novel POU1F1
      mutations were detected in Israeli patients with CPHD. Two of them, a W193X
      missense mutation and a deletion of two adenine bases at position 242Q, may lead
      to the production of a truncated protein that lacks the entire POU homeodomain or
      part of it, respectively. The third mutation, F262L, resides in the POU
      homeodomain and hence might change the activity of the protein.

PMID- 15844474
TI  - Psychological adjustment of children with short stature: a comparison of clinic
      referred children with short stature and type 1 diabetes mellitus.
AB  - This study compared the psychological adjustment between children with short
      stature and youth with type 1 diabetes mellitus (DM1). The Child Behavior
      Checklist, Children's Depression Inventory, Social Anxiety Scale for Children-
      Revised, and Asher Loneliness Scale were administered to 58 children (26 with
      short stature and 32 with DM1) and a parent during a regularly scheduled clinical
      appointment for endocrinology care. Results show that the parents of children
      with short stature rated their children as having more social, thought, and
      attention problems, and exhibiting greater delinquent behavior, as compared to
      parental ratings of children with DM1. No diagnostic group differences in child
      or parent-rated internalizing symptoms were found. Implications of these findings
      for personnel working with children with short stature are discussed.

PMID- 15844475
TI  - 17alpha-hydroxylase/17,20-Lyase deficiency due to novel compound heterozygote
      mutations: treatment for tall stature in a female with male pseudohermaphroditism
      and spontaneous puberty in her affected sister.
AB  - We report on two German sisters with deficiency in the 17alpha-hydroxylase/17,20
      lyase enzyme corresponding to typical hormone profile. A paternal nonsense
      mutation R388X in exon 7 and a maternal missense mutation P428L in exon 8 of the
      CYP17 gene have been identified in both girls. Residual in vitro 17alpha
      hydroxylase activity for the conversion of [3H]-Preg to [3H]-17OH-Preg has been
      detected in transfected 293-cells expressing P428L mutant enzyme; however, no
      17,20-lyase activity was observed converting [3H]-17OH-Preg into [3H]-DHEA. The
      46,XX-sister spontaneously entered puberty. The 46,XY-sister with a predicted
      adult height of 203 cm was treated with a high dose of conjugated estrogens and
      resulted with a final height of 186.9 cm. The present data suggest that compound
      heterozygous 46,XX females bearing a P428L allele may develop spontaneous onset
      of puberty. Furthermore, in 46,XY females with tall stature, treatment with
      conjugated estrogens may lead to a significant reduction of their predicted adult
      height.

PMID- 15844476
TI  - A patient with Klinefelter's syndrome and thalassemia intermedia.
AB  - Klinefelter's syndrome (KS) is associated with a wide spectrum of clinical
      features, such as tall stature, eunuchoid proportions, testes disproportionately
      small for the level of pubertal development, gynecomastia and behavioral
      problems. The association of KS with thalassemia intermedia has not been
      previously reported. A male patient with thalassemia intermedia was diagnosed
      with KS at the age of 14 years when endocrine evaluation for delayed puberty
      showed hypergonadotrophic hypogonadism. Thyroid function was normal; however,
      basal and GnRH-stimulated gonadotropin concentrations were raised while serum
      testosterone was low. Karyotype analysis revealed KS (47,XXY). Testosterone
      replacement therapy started soon after diagnosis and now at the age of 20 years
      the patient's height is 178.3 cm, the U/L ratio is 0.91. Testicular volume is 12
      ml (Prader orchidometer) and his pubic hair is stage 4. To our knowledge this is
      the first case of a patient suffering from KS and thalassemia intermedia reported
      in the literature.

PMID- 15844477
TI  - Clinically significant gynecomastia in a newborn with congenital heart disease.

PMID- 15844478
TI  - 18q deletion syndrome associated with autoimmune thyroid disease presenting as
      hyperthyroidism.

PMID- 15844479
TI  - Chromatography of plasmid DNA.
AB  - Liquid chromatography plays a central role in process-scale manufacturing of
      therapeutic plasmid DNA (pDNA) for gene therapy and DNA vaccination. Apart from
      its use as a preparative purification step, it is also very useful as an
      analytical tool to monitor and control pDNA quality during processing and in
      final formulations. This paper gives an overview of the use of pDNA
      chromatography. The specificity of pDNA purification and the consequent
      limitations to the performance of chromatography are described. Strategies
      currently used to overcome those limitations, as well as other possible solutions
      are presented. Applications of the different types of chromatography to the
      purification of therapeutic pDNA are reviewed, and the main advantages and
      disadvantages behind each technique highlighted.

PMID- 15844480
TI  - In situ determination of adsorption kinetics of proteins in a finite bath.
AB  - A method for fast in situ measurement of adsorption kinetics based on a finite
      bath was developed. We modified the conventional finite bath by replacing the
      external loop by a dip probe which enables in situ measurement of the
      concentration change in the contactor. Deposition of adsorbent particles on the
      reflection surface of the dip probe compromised measurements. Different
      membranes, a polyamide, a polypropylene and a nylon membrane were tested to
      protect the internal reflection surface of the dip probe from fouling with
      adsorbent particles. The nylon membrane provided efficient protection and high
      mass transfer evaluated by response time experiments. Unspecific adsorption of
      the model protein on the membrane could also be excluded. To corroborate the
      measurements of the dip probe the results were compared to a conventional finite
      bath and to a shallow-bed. The uptake curves for human polyclonal IgG at
      different concentrationes (0.1-3 g/l) on rProtein A Sepharose FF and MabSelect
      were used as model system. The effective diffusion coefficients were determined
      using a pore diffusion model. These values were in good agreement for all
      methods.

PMID- 15844481
TI  - Effect of the flow rate on the measurement of adsorption data by dynamic frontal
      analysis.
AB  - The adsorption data of propyl benzoate were acquired by frontal analysis (FA) on
      a Symmetry-C18 column, using a mixture of methanol (65%, v/v) and water as the
      mobile phase, at three different flow rates, 0.5, 1.0 and 2.0 mL/min. The exact
      flow rates Fv were measured by collecting the mobile phase in volumetric glasses
      (deltaFv / Fv < or = 0.2%). The extra-column volumes and the column hold-up
      volume were accurately measured at each flow rate by tracer injections. The
      detailed effect of the flow rate on the value of the amount adsorbed was
      investigated. The best isotherm model accounting for the adsorption data was the
      same BET isotherm model at all three flow rates. Only slight differences (always
      less than 5%) were found between the three different sets of isotherm parameters
      (saturation capacity, q(s), equilibrium constant on the adsorbent, b(s) and
      equilibrium constant on successive layers of propyl benzoate, bL). The
      reproducibility of the same isotherm parameters measured by the inverse method
      (IM) is less satisfactory, leading to R.S.D.s of up to 10%. A flow rate increase
      is systematically accompanied by a slight increase of the amount adsorbed. This
      phenomenon is consistent with the influence of the pressure on the equilibrium
      constant of adsorption due to the difference between the partial molar volumes of
      the solute and the adsorbate. The larger average pressure along the column that
      is required to achieve a larger flow rate causes a larger amount of solute to be
      adsorbed on the column at equilibrium. This result comforts the high sensitivity
      and versatility of the FA method for isotherm determination under any kind of
      situation.

PMID- 15844482
TI  - Properties and performance of novel high-resolution/high-permeability ion
      exchange media for protein chromatography.
AB  - There is continued interest in the development of stationary phases for protein
      chromatography that can provide high resolution at elevated flow rates of the
      mobile phase. When using porous particles, resolution and dynamic binding
      capacity decline rapidly as the flow rate is increased. Monolithic columns have
      been developed to overcome these limitations. However, there are difficulties in
      manufacturing homogeneous larger scale monoliths. In this paper we investigate
      the morphology and performance characteristics of columns based on new ion
      exchangers obtained by mechanically disrupting continuous beds of acrylamido
      based polymeric media. Near colloidal suspensions of loose particles obtained
      with this procedure can be flow-packed in ordinary chromatography columns
      resulting in beds of unexpectedly high hydraulic permeability. Columns up to 2.2
      cm in diameter were studied with both Q and S functionalized media. The hydraulic
      permeability and interparticle porosity of these columns were rather high. The
      permeabilities of the S and Q media were 1.5 x 10(-13) and 2.4 x 10(-13) m2,
      respectively, while the corresponding porosities were 60 and 70%. These porosity
      values are similar to those of monoliths, suggesting that these particles
      assemble under flow to give high-porosity bridged structures. The structure of
      these packed beds was further characterized by embedding small packed columns in
      resins and obtaining sections for microscopic observation. The sections reveal
      the presence of small aggregates of non-porous 1-3 microm particles, surrounded
      by flow channels several micrometers in size. The height equivalent to a
      theoretical plate under isocratic and gradient elution conditions and the dynamic
      binding capacity were determined for several proteins and were found to be
      virtually independent of flow.

PMID- 15844483
TI  - Evaluating and monitoring the packing behavior of process-scale chromatography
      columns.
AB  - The packing characteristics of process-scale chromatography columns were
      evaluated using the responses to conductivity-based pulse and step inputs derived
      from tracer experiments and in-process transitions (i.e. column equilibration and
      regeneration steps). Characteristics of the measured residence time distributions
      (RTDs) were quantified by statistical moments and using the equations derived
      from the Gaussian model. The first and second moments calculated from in-process
      step transitions for multiple runs were in good agreement with those moments
      calculated from the pulse-input experiments conducted immediately after column
      packing. This indicates that most of the time the bed behavior at the time of
      packing is consistent with that at the time of operation. Due to the significant
      resistance to protein mass transfer inside the particles, estimated plate heights
      for protein solutes are expected to be much greater than those observed from the
      experiments using saltbased tracers. Thus, the column efficiency derived from
      salt-based experiments can be a useful measure of packing consistency rather than
      a significant parameter influencing the outcome of protein separations.

PMID- 15844484
TI  - Comparison of chromatographic ion-exchange resins IV. Strong and weak cation
      exchange resins and heparin resins.
AB  - A comparative study was performed on heparin resins and strong and weak cation
      exchangers to investigate the pH dependence, efficiency, binding strength,
      particle size distribution, static and dynamic capacity, and scanning electron
      microscopy pictures of chromatographic resins. The resins tested include: Heparin
      Sepharose FF, SP Sepharose FF, CM Sepharose FF, Heparin Toyopearl 650 m, SP
      Toyopearl 650 m, CM Toyopearl 650 m, Ceramic Heparin HyperD M, Ceramic S HyperD
      20, and Ceramic CM HyperD F. Testing was performed with four different proteins:
      anti-FVII Mab (IgG), aprotinin, lysozyme, and myoglobin. Dependence of pH on
      retention was generally very low for proteins with high isoelectric point (pI),
      though some decrease of retention with increasing pH was observed for CM Ceramic
      HyperD F and S Ceramic HyperD 20. Binding of anti-FVII Mab with pI < 7.5 was
      observed on several resins at pH 7.5. Efficiency results show the expected trend
      of increasing dependence of the plate height with increasing flow rate of Ceramic
      HyperD resins followed by Toyopearl 650 m resins and the highest flow dependence
      of the Sepharose FF resins corresponding to their pressure resistance.
      Determination of particle size distribution by two independent methods, coulter
      counting and SEM, was in good agreement. Binding strength of cation-exchange
      resins as a function of ionic strength varies depending on the protein. Binding
      and elution at high salt concentration may be performed with Ceramic HyperD
      resins, while binding and elution at low salt concentration may be performed with
      model proteins on heparin resins. Employing proteins with specific affinity for
      heparin, a much stronger binding is observed, however, some cation exchangers may
      still be good substitutions for heparin resins. Dynamic capacity at 10%
      breakthrough compared to static capacity measurements and dynamic capacity
      displays that approximately 40-80% of the total available capacity is utilized
      during chromatographic operation depending on flow rate. A general good agreement
      was obtained between results of this study and data obtained by others. Results
      of this study may be used in the selection of resins for testing during protein
      purification process development.

PMID- 15844486
TI  - Influence of particle diameter distribution on protein recovery in the expanded
      bed adsorption process.
AB  - The General Rate model has been developed and solved to describe protein
      adsorption in an expanded bed. The model takes into account axial and local
      variation of particle size distribution (PSD), external and intra-particle mass
      transfer resistances, and dispersion in liquid phase. The influence of PSD on
      breakthrough profiles has been analysed. The simulation results show that for a
      significantly high expanded bed the lower part of the breakthrough curve
      profiles, calculated for local particle size distribution (LPSD) and for axial
      average particle size distribution (APSD) are very similar. However, the upper
      part of breakthrough profiles calculated for LPSD approaches inlet concentration
      much more slowly than those calculated for APSD. The retention times of the lower
      part of uptake curves calculated with average particle diameter are constantly
      shorter than those obtained from LPSD. For the calculation of the dynamic
      capacity (DC), the LPSD can be replaced by APSD for large expanded bed heights.
      Using breakthrough profiles calculated for average particle size, DC values are
      constantly underestimated.

PMID- 15844485
TI  - Impact of multiple re-use of anion-exchange chromatography media on virus
      removal.
AB  - We evaluated viral clearance in multiply-cycled anion-exchange media run in flow
      through mode. We found that anion-exchange columns do not lose viral clearance
      capacity after extensive re-use, if they are cleaned with recommended buffers
      that do not chemically degrade the media. In contrast, anion-exchange (AEX)
      columns that are not cleaned or are cleaned with buffers that chemically degrade
      the media lost viral clearance capacity after extended use. In these cases, other
      performance attributes that changed at the same time were increased band
      spreading, decreased DNA clearance and accumulating backpressure that prevented
      re-use past 80-120 cycles. Thus, our data suggests that flow through mode anion
      exchange columns that are cleaned with recommended cleaning buffers, and
      periodically monitored for band spreading, DNA clearance and/or backpressure need
      not be re-evaluated for viral clearance at the end of the validated media
      lifetime.

PMID- 15844487
TI  - Optimization of monoclonal antibody purification by ion-exchange chromatography.
      Application of simple methods with linear gradient elution experimental data.
AB  - Simple methods for the optimization of ion-exchange chromatography of proteins in
      our previous papers were applied to cation-exchange chromatography purification
      of monoclonal antibodies (Mab). We carried out linear gradient elution
      experiments, and obtained the data for the peak salt concentration and the peak
      width. From these data, the distribution coefficient as a function of salt
      concentration, and the height equivalent to a theoretical plate (HETP) as a
      function of mobile phase velocity were calculated. The optimized linear gradient
      elution conditions were determined based on the relationship between buffer
      consumption and separation time. The optimal stepwise elution conditions were
      determined based on the relationship between the distribution coefficient and the
      salt concentration.

PMID- 15844488
TI  - Lysozyme purification from tobacco extract by polyelectrolyte precipitation.
AB  - Tobacco is widely used as a model plant for feasibility studies of recombinant
      protein production from transgenic plants. However, dealing with large quantities
      of biomass to recover recombinant proteins is a challenge for down-stream
      processing. In this study, the effect of isoelectric precipitation on native
      tobacco protein was first studied. Among the three acids studied, hydrochloric
      acid is shown to be more effective than acetic or citric acid, and at pH 4, 60%
      of native tobacco protein was precipitated by HCl. Egg white lysozyme was used as
      the model protein to test the feasibility of polyelectrolyte precipitation in
      protein recovery from tobacco extract. Precipitation of lysozyme at pH 7 was
      shown ineffective probably because of the interference of polyphenolic acids.
      However, after isoelectric precipitation at pH 5 poly(acrylic) acid (PAA) was
      shown to precipitate 85% of the soluble lysozyme when the polymer dosage was
      increased to 1.5 mg polymer/mg lysozyme, while negligible amounts of native
      tobacco protein was co-precipitated. Lysozyme precipitation by PAA in tobacco
      extract obtained at pH 5 was also studied, and lysozyme yield was significant
      improved.

PMID- 15844489
TI  - Applicability of the stoichiometric displacement model to description of the
      retention behavior of charged-fusion proteins during fast protein liquid
      chromatography.
AB  - The applicability of the stoichiometric displacement model (SDM) to description
      of the retention behavior of charged-fusion proteins in large ion exchange resin
      (approximately 90 microm diameter) packed column was studied. Proteins were
      characterized by SDM for isocratic elution. The parameters were subsequently used
      to evaluate their suitability in predicting protein retention and peak width
      under gradient elution. The proteins were beta-glucuronidase (GUS) and its
      fusions with polypeptides of 5, 10 and 15 aspartic acids at the C-terminal of the
      wild-type GUS. Predictions of retention time were within 10% of the experiment
      results. The plate number obtained at high salt concentration from isocratic
      elution was used as a first estimate for predictions of peak width. The results
      show that the SDM is sufficient to describe the binding equilibrium of fusion
      proteins in ion-exchange columns packed with large resin particles. In addition,
      the binding mechanism between fusion proteins and the ion exchanger is explored
      with the assistance of comparative molecular modeling.

PMID- 15844490
TI  - Protein adsorption on the mesoporous molecular sieve silicate SBA-15: effects of
      pH and pore size.
AB  - A mesoporous molecular sieve silicate, SBA-15, with three pore sizes (38.1 A,
      77.3 A, and 240 A) has been synthesized using a non-ionic, tri-block copolymer as
      a template in a sol-gel method. The effects of synthesis conditions on the pore
      size and pore-size distribution of this adsorbent have been described. The
      adsorption of proteins on these crystalline, ordered, materials has been studied.
      The kinetics of adsorption and equilibrium capacity have been probed with three
      proteins of different dimensions. The effects of electrostatic interactions and
      protein size are illustrated. It has been shown that SBA-15 materials can be
      tailored to show size selectivity for proteins, and very high capacities (450
      mg/g) can be obtained. Furthermore, the rates of adsorption are shown to be
      dependent on the pore size, protein structure and solution pH.

PMID- 15844491
TI  - Sorption behaviour of bifenthrin on cork.
AB  - Biphentrin, a known pyrethroid, was studied, aiming its removal from aqueous
      solutions by granulated cork sorption. Batch experiments, either for equilibrium
      or for kinetics, with two granulated cork sizes were performed and results were
      compared with those obtained with of activated carbon sorption. Langmuir and
      Freundlich adsorption isotherms were obtained both showing high linear
      correlations. Bifenthrin desorption was evaluated for cork and results varied
      with the granule size of sorbent. The results obtained in this work indicate that
      cork wastes may be used as a cheap natural sorbent for bifenthrin or similar
      compounds removal from wastewaters.

PMID- 15844492
TI  - Observation of cerium isotope fractionation in ion-exchange chromatography of
      Ce(III)-malate complex.
AB  - The cerium isotope fractionation between Ce(III)-malate complex in aqueous
      solution and cerium ions in a cation-exchange resin was conducted by displacement
      chromatography. The pH and the chemical composition of the eluent were optimized
      for maintaining the self-sharpening band boundaries and the 21 m chromatographic
      migration of the Ce band underwent. Graphite slurry was coated on the tantalum
      filament prior to sample loading for reducing the isobaric interferences in
      cerium isotopic ratio determination by mass spectrometry. From the experimental
      results, it was found that the heavier isotope was enriched in the front boundary
      part of the cerium adsorption band, which meant that the heavier isotope was
      preferentially fractionated into the Ce3+ malate complex rather than simply
      hydrated Ce3+ ions. The isotope separation coefficient for the 136Ce/140Ce and
      142Ce/140Ce was 5.2 x 10(-5) and -1.9 x 10(-5), respectively, at 298 K.

PMID- 15844493
TI  - Novel simulated moving-bed adsorber for the fractionation of gas mixtures.
AB  - The separation of propylene-propane mixture is an energy intensive operation
      commercially practiced using cryogenic distillation. The separation by pressure
      swing adsorption has been studied as an alternative. A fixed-bed pressure swing
      adsorption yields the heavy component as a pure product. The product recovery and
      the productivity are not high. In a moving-bed process, because of the counter
      current solid-gas contact, the separation achieved is similar to that of the
      fractionation by distillation. Although the moving-bed operation offers the upper
      limit for the performance of a cyclic adsorptive process, due to mechanical
      complexities in the handling of solids the 'simulated' moving-bed is preferred.
      By moving the inlet and outlet ports of streams located along the length of the
      bed, a moving-bed process can be realized in a fixed bed. We describe here a
      'moving-port' system which permits injection or withdrawal of the fluid along the
      axial direction in a fixed bed. A fixed bed embedded with the moving-port systems
      emulates a simulated moving-bed adsorber. The proposed adsorber can fractionate a
      binary gas mixture into two product streams with high purities. It is similar to
      the Sorbex process of UOP but does not have the eluent as an additional
      separating agent. A parametric study indicates that high purity products and a
      higher productivity by an order of magnitude can be achieved with simulated
      moving-beds compared to the fixed beds.

PMID- 15844494
TI  - Evidence based diagnosis and treatment of rhinosinusitis and nasal polyps.

PMID- 15844495
TI  - Functional endoscopic sinus surgery: 5 year follow up and results of a
      prospective, randomised, stratified, double-blind, placebo controlled study of
      postoperative fluticasone propionate aqueous nasal spray.
AB  - One hundred nine patients with chronic rhinosinusitis underwent functional
      endoscopic sinus surgery. Seventy seven patients had polyposis. The population
      was studied prospectively for 5 years postoperatively. Seventy two patients
      attended the 5 year follow-up visit. At 1, 2, 3, 4 and 5 years of follow-up all
      outcome measures except olfactory detection thresholds (visual analogue scores,
      endoscopic findings, nasal mucociliary clearance times, total nasal volumes) were
      significantly improved compared to preoperative baseline values. Olfactory
      detection thresholds were significantly improved at 1 and 2 years postoperation.
      Patient symptom scores were improved in a greater percentage of patients than
      more objective outcome measures. Thirty eight patients required a total of 88
      postoperative rescue medication courses with prednisolone and antibiotic. Twelve
      patients failed the study as they required at least 1 rescue medication course a
      month for 2 consecutive months. We demonstrated an 89% 5 year "survival" rate
      with regards to the risk of failure. The patients were also entered into a
      randomised, stratified, prospective, double-blind, placebo controlled study of
      fluticasone propionate aqueous nasal spray 200 mcg twice daily, commencing 6
      weeks after FESS, with a 5 year follow-up. The change in overall visual analogue
      score was significantly better in the FPANS group at 5 years. The changes in
      endoscopic oedema and polyp scores and in total nasal volumes were significantly
      better in the FPANS group at 4 years but not 5 years. Last value carried forward
      analysis demonstrated that changes in endoscopic polyp score and in total nasal
      volume was significantly better in the FPANS group at 5 years. Significantly more
      prednisolone rescue medication courses were prescribed in the placebo group. Of
      the 12 patients who failed the study, 10 were in the placebo group. This
      difference nearly achieved significance.

PMID- 15844496
TI  - Correlation between the cytology of the nasal middle meatus and BAL in chronic
      rhinosinusitis.
AB  - The relation between chronic rhinosinusitis (CRS) and the associated lower
      airways involvement is not clear yet. In this context, the aim of this
      prospective study was to evaluate the correlation between middle meatal lavage
      (MML) and bronchoalveolar lavage (BAL) cytology in adult CRS patients. Based on
      clinical history and pulmonary function changes, CRS patients were divided into
      three subgroups: asthma, small airway disease (SAD) and normal lower airway (NLA)
      subgroups. Preoperatively, 50 MMLs and 25 BALs were performed in 25 CRS patients
      scheduled for FESS. At 1000X power microscopic magnifications, 48 MML and 24 BAL
      cytospin slides were examined for total and differential cell counts (DCC). This
      study showed that eosinophils were the dominant inflammatory cells in MMLs of the
      asthma subgroup and were significantly correlated to FEVI (p = 0.042) and
      Tiffineau index (p = 0.037). On the other hand, neutrophils were the dominant
      inflammatory cells in MMLs of the SAD subgroup and significantly correlated to
      FEF75% and Tiffinau index (p = 0.013 and p = 0.012 respectively). There was no
      significant correlation between MML and BAL cell differential counts in CRS
      patients (p > 0.05). The data showed that the lower airways involvement in CRS
      patients could be related to the dominant type of inflammatory cells in the upper
      airways.

PMID- 15844497
TI  - Nitric oxide production in the sphenoidal sinus by the inducible and constitutive
      isozymes of nitric oxide synthase.
AB  - OBJECTIVE: To study the production of nitric oxide (NO), and the presence of
      different isoforms of the NO-synthesising enzyme, NO-synthase (NOS), in the
      paranasal sinus. MATERIALS AND METHODS: Ten patients, undergoing surgery for
      pituitary adenoma, were examined for the presence of NO gas in the sphenoidal and
      maxillary sinus. The distribution of different NOS isozymes in mucosal biopsies
      from sphenoid and maxillary sinus and ethmoidal cells was studied. RESULTS: The
      mean concentration of NO was 2575 ppb in the sphenoidal sinus and 6792 ppb in the
      maxillary sinus. Morphological analyses revealed intense NADPH-diaphorase
      staining throughout the epithelium. Immunoreactivity against NOS2 (inducible NOS)
      was observed in the apical cell layer but not of the basal layer. NOS1 (neuronal
      NOS)-immunoreactivity was mainly seen in the subapical part of the epithelium and
      NOS3 (endothelial NOS)-immunoreactivity was observed only in the most apical part
      of the epithelium. CONCLUSION: NO concentration in the sphenoidal sinus is about
      the same as in the nasal cavity and approximately half of the concentration found
      in the maxillary sinus. All of the three main different isozymes of NOS can be
      demonstrated in the mucosa of the sphenoidal and maxillary sinus and ethmoidal
      cells, NOS2 being the most abundant isoform.

PMID- 15844498
TI  - Numerical simulation of intranasal air flow and temperature after resection of
      the turbinates.
AB  - BACKGROUND: Radical surgical resection of the turbinates leads to a reduced
      intranasal air conditioning. The aim of this study was to determine the effect of
      turbinate resection on intranasal heating and airflow patterns using a numerical
      simulation. METHODS: A bilateral model of the human nose with resection of the
      turbinates on one side based on a CT-scan was reconstructed. A numerical
      simulation applying the computational fluid dynamics (CFD) solver Fluent 6.1.22
      was performed displaying inspiratory intranasal air temperature and airflow
      patterns. RESULTS: Due to resection of the turbinates the airflow pattern is
      disturbed resulting in a spacious vortex throughout the entire nasal cavity.
      Hence, contact between air and surrounding nasal wall is less intense.
      Consequently, intranasal heating of the inspired air is relevantly reduced.
      CONCLUSIONS: Surgical resection of the turbinates leads to a disturbed intranasal
      air conditioning. The presented numerical simulation demonstrates the close
      relation between airflow patterns and heating.

PMID- 15844499
TI  - Dynamics of airborne pollen particles from inhalation to allergic reaction in the
      nose.
AB  - BACKGROUND: Pollinosis is common worldwide, and has been frequently studied.
      However, the intranasal dynamics of pollen grains have not yet been documented.
      The purpose of this study is to elucidate for the first time the dynamics of
      Japanese cedar pollen (JCP) in the human nose at consecutive steps from
      inhalation to allergic reaction together with release of Cry j 1 (a major
      allergenic component of JCP) in the nose. METHODS: A personal sampler collected
      airborne pollens at head height outdoor on the street, while intranasal pollens
      after natural or experimental inhalation were collected by irrigation with 200ml
      saline. Cry j 1 in the supernatant after in vitro incubation with phosphate
      buffered saline or lavage was determined by enzyme-linked immunoassay. RESULTS:
      Head-height pollen was 183.0 +/- 43.1/300L/h, with 99% of the inhaled pollens
      deposited on the nasal surface. Eighty eight% of the inhaled pollen was
      transported to the out-side of the nose by ciliary function within 3 hours.
      During this process, considerable amounts of Cry j 1 were released in the nose
      reaching its plateau within 30 min. When the number of pollen deposited exceeded
      more than approximately 65 particles, symptoms may occur, leading presumably up
      to a 74% reduction of the intra-nasal pollen. CONCLUSION: The majority of inhaled
      airborne pollens was deposited on the nasal mucosal surface and moved out from
      the nose by mucociliary transportation. During this process, when allergenic
      substances are released up to a critical concentration, allergic reactions occur
      leading to expelling of pollen from the nose followed by subsiding of the
      symptoms.

PMID- 15844500
TI  - Paranasal sinus fungus ball and surgery: a review of 175 cases.
AB  - OBJECTIVE: To analyze the surgical results after Functional Endoscopic Sinus
      Surgery (FESS) in patients with paranasal sinus fungus ball. MATERIAL AND
      METHODS: Retrospective analysis of the results of FESS performed in 175 patients
      suffering from paranasal sinus fungus balls. RESULTS: All maxillary (n = 150),
      sphenoidal (n = 20), and ethmoidal (n = 4) locations have been treated
      exclusively by FESS to obtain a wide opening of the affected sinuses, allowing a
      careful extraction of all fungal material without removal of the inflamed mucous
      membrane. No major complication occurred. Postoperative care was reduced to nasal
      lavage with topical steroids for 3 to 6 weeks. Only 1 case of local failure have
      been observed (maxillary sinus, n = 1), and 6 cases of persisting of fungus ball
      (maxillary sinus, n = 4; frontal sinus, n = 2) with a mean follow-up of 5 years.
      No medical treatment (antibiotic, antifungal) was required. CONCLUSION: Surgical
      treatment of a fungus ball consists in opening the infected sinus cavity at the
      level of its ostium and removing fungal concretions while sparing the normal
      mucosa. No antifungal therapy is required. Finally, through this 175 patients
      study, FESS appears a reliable and safe surgical treatment with a low morbidity.

PMID- 15844501
TI  - Natural history and control of epistaxis in a group of German patients with Rendu
      Osler-Weber disease.
AB  - INTRODUCTION: Epistaxis is the most common symptom of a complex, genetically
      determined vasculopathy, which is known under the notion hereditary hemorrhagic
      telangiectasia (HHT, Rendu-Osler-Weber-syndrome). This study was initiated to
      gain more knowledge about the natural history of epistaxis in a German HHT
      population. PATIENTS AND METHODS: Data of 49 HHT patients were ascertained by
      interviewing these patients with a standardized disease specific questionnaire.
      Patients' files were retrospectively reviewed for data concerning age, gender,
      past medical history, laboratory parameters, number of hospital admissions for
      epistaxis, conservative and operative types of therapy, treatment results and
      follow-up. MAIN RESULT: Epistaxis was the first and most prominent symptom in 93%
      of the patients and could be triggered most frequently by stress. Half of the
      patients had experienced first episodes of epistaxis in childhood, but usually
      epistaxis did not become troublesome before the age of 35 years. The effects of
      hormonal changes or therapies with systemic hormones were inconclusive with
      regard to impact on epistaxis. Patients with septal perforations had to be
      admitted for inpatient epistaxis treatment more frequently than patients with an
      intact nasal septum. An overall reduction of frequency and intensity of epistaxis
      could be achieved in 89% of the patients through the daily use of nasal
      lubricants and a minimum of two treatment sessions with the Nd:YAG laser. However
      in none of the cases the treatment results were permanent. More than 50% of the
      patients, who had been screened for visceral arteriovenous malformations, were
      positive for pathologic vascular lesions. PRINCIPAL CONCLUSION: The natural
      history of epistaxis in German HHT patients is similar to previously described
      entities from other parts of the world. First clinical signs of HHT may be
      present at an earlier age than previously thought.

PMID- 15844502
TI  - Symptomatic and pathophysiological observations in a modified animal model of
      allergic rhinitis.
AB  - There are many animal models for studying allergic rhinitis. However, they either
      need a too long establishment period or fail to show significant late allergic
      responses. In the model described in this paper, guinea pigs were sensitized and
      challenged intranasally with ovalbumin according to a modified protocol. As
      controls, antihistamine-treatment and non-sensitized, non-treatment groups were
      studied in parallel. Early and late symptoms, passive cutaneous anaphylaxis (PCA)
      reaction, nitric oxide synthase (NOS) immunoreactivities, pathological changes in
      nasal mucosa and nasal lavage fluid (NLF), and histamine, TXB2 and p-LTs levels
      in NLF were evaluated. In contrast to the control groups, the model group
      exhibited typical symptoms, including late phase nasal blockage, and increased
      levels of IgG1 and IgE. Considerable eosinophil infiltration and eNOS
      immunoreactivities in nasal mucosa, and increased levels of histamine, TXB2 and p
      LTs in NLF were also observed. This model was not only capable of showing
      satisfactory symptomatic and pathophysiological changes in allergic rhinitis but
      also showed good responses to antihistamine treatment. The model can be
      established in six weeks. For the first time, respiratory rate was employed as an
      index to reflect the nasal blockage of guinea pigs and it proved to be a reliable
      indicator.

PMID- 15844503
TI  - Study on the reproducibility of the Waters' views of the maxillary sinuses.
AB  - OBJECTIVE: This study intended to investigate the reproducibility of the Waters'
      view for maxillary sinusitis and to define its place in clinical practice.
      MATERIALS AND METHOD: Radiographs of 80 maxillary sinuses of patients with
      suspected acute sinusitis were read by 6 radiologists, 6 ENT surgeons, 6 general
      practitioners (GPs). Interobserver agreement was calculated using the kappa
      statistic. RESULTS: Agreement was good (kappa = 0.63; 95% CI 0.58-0.68) between
      radiologists when the criteria used to define acute sinusitis were "important
      mucosal swelling, air-fluid level or complete opacity". When the criteria "air
      fluid level or complete opacity" were used, agreement was fair (kappa 0.39; 95%
      CI 0.35-0.44). Between ENT-surgeons kappas were respectively 0.58 (95% CI 0.53
      0.63) and 0.37 (95% CI 0.32-0.42). Between GPs kappas were respectively 0.30 (95%
      CI 0.25-0.35) and 0.28 (95% CI 0.23-0.33). CONCLUSION: The reproducibility of
      Waters' views of the maxillary sinuses is best when the interpretation is
      performed by radiologists or ENT surgeons, and when criteria for sinusitis are:
      important mucosal swelling, air fluid level or complete opacity. The good
      interobserver agreement combined with the known high negative predictive value of
      these diagnostic criteria makes the Waters' view only useful for ruling out acute
      sinusitis.

PMID- 15844504
TI  - Expression of somatostatin receptors in arginine vasopressin hormone-secreting
      olfactory neuroblastoma--report of two cases.
AB  - OBJECTIVE: Arginine vasopressin hormone-secreting olfactory neuroblastomas are
      extremely rare, with fewer than twenty cases reported in the literature. Two of
      these cases, both initially presenting with the syndrome of inappropriate
      antidiuretic hormone, are presented. The second tumour was successfully
      identified using somatostatin receptor (octreotide) radiographic scintography.
      METHOD: The pathological specimens from both cases were examined
      immunohistochemically for somatostatin receptors. RESULTS: Samples from both
      cases demonstrated positivity for somatostatin receptors. CONCLUSIONS: This
      report demonstrates the potential use of somatastatin analogues in the
      investigation, follow-up and treatment of patients with olfactory neuroblastoma.

PMID- 15844505
TI  - Nasal septum giant pyogenic granuloma after a long lasting nasal intubation: case
      report.
AB  - The authors present a case of Pyogenic Granuloma (PG) arising from the nasal
      septum in the posterior nasal cavity of a patient male sex, caucasian, 32 years
      old, with a previous history of cranioencephalic trauma, several neurosurgeries
      for different subsequent neurological problems and the use of a nasogastric tube
      for feeding (nasal intubation) during 30 days. He underwent surgery in St.
      Vincent de Paul Hospital (Rio de Janeiro) on May 18, 1993, for the tumor removal
      and straightening of the nasal septum. Under endoscopic guidance the complete
      excision of the tumor mass was perfectly done thanks to the excellent exposure of
      the lesion, provided by the enlarged telescopic view, and the wide access
      afforded by the septum straighttening plus the cartilaginous septum mobilization
      through the maxilla-premaxilla approach of Cottle, allied to the lateralization
      and volume reduction of the right inferior nasal concha, simultaneously
      performed, thus making lateral rhinotomy or "degloving" unnecessary. The patient
      is until now (2004) completely free of the lesion operated on. This is the first
      report in the literature of such a lesion associated to nasal intubation as the
      triggering agent.

PMID- 15844506
TI  - Mycobacterial spindle cell pseudotumor (MSP) of the nasal septum clinically
      mimicking Kaposi's sarcoma: case report.
AB  - Mycobacterial spindle cell pseudotumor (MSP) is a rare benign lesion
      characterised by local proliferation of spindle--shaped histiocytes containing
      acid--fast atypical mycobacteria, clinically resembling Kaposi's sarcoma. Most
      cases of MSP reported so far affected immunodeficient patients or patients
      receiving immunosuppressive medication. We report a case of MSP affecting the
      nasal septum of a 76-year-old man, a location that has not been published so far
      concerning the manifestation of MSP. In conclusion, our case report points toward
      MSP as a very rare pseudomalignant lesion that should be included into
      deliberations concerning the differential diagnosis of circumscribed expansile
      nodular proliferations of the nasal septum clinically mimicking Kaposis's sarcoma
      or other mesenchymal neoplasms.

PMID- 15844507
TI  - Meeting of the General Assembly of ERS: Istanbul, June 23, 2004.

PMID- 15844508
TI  - Liquid chromatography-tandem mass spectrometry for the analysis of pharmaceutical
      residues in environmental samples: a review.
AB  - Pharmaceutical residues are environmental contaminants of recent concern and the
      requirements for analytical methods are mainly dictated by low concentrations
      found in aqueous and solid environmental samples. In the current article, a
      review of the liquid chromatography-tandem mass spectrometry (LC-MS/MS) based
      methods published so far for the determination of pharmaceuticals in the
      environment is presented. Pharmaceuticals included in this review are
      antibiotics, non-steroidal anti-inflammatory drugs, beta-blockers, lipid
      regulating agents and psychiatric drugs. Advanced aspects of current LC-MS/MS
      methodology, including sample preparation and matrix effects, are discussed.

PMID- 15844509
TI  - Analytical strategies for residue analysis of veterinary drugs and growth
      promoting agents in food-producing animals--a review.
AB  - After a brief introduction into the field of veterinary drugs and growth
      promoting agents, the most important EU regulations and directives for the
      inspection of food-producing animals and animal products regarding the residue
      control of these substances are presented and discussed. Main attention in the
      review is on the methods of analysis in use today for the most important classes
      of veterinary drugs and growth-promoting agents viz. anthelmintics, antibiotics,
      coccidiostats, hormones, beta-agonists and tranquillizers. Emphasis is given to
      the potential, and limitations, of state-of-the-art analytical procedures and
      their performance characteristics. The most obvious conclusion is that, today
      (reversed-phase) liquid chromatography combined with tandem mass spectrometric
      detection--either triple-quadrupole or ion-trap multi-stage--is the preferred
      technique in a large majority of all cases. In the field of sample treatment, the
      combined use of liquid extraction--i.e., liquid partitioning or liquid-liquid
      extraction--and liquid-solid extraction--primary on- or off-line solid-phase
      extraction--is most popular. Finally, while the analytical tools required to meet
      the demands typically formulated by governments and international organizations
      today, generally speaking are available, several problems still do exist. To
      quote three examples, problems are encountered in the area of simultaneously
      extracting and pre-treating groups of analytes with mutually widely different
      polarities, with regard to identification-point--based confirmation of analyte
      identity, and regarding quantification errors caused by ion-suppression effects.
      Improving the speed of analysis is another aspect that should, and will, receive
      dedicated interest in the near future.

PMID- 15844510
TI  - Structure elucidation of phase II metabolites by tandem mass spectrometry: an
      overview.
AB  - The present paper provides a summary of the collision-induced dissociation of
      protonated and deprotonated phase II metabolites of drugs and pesticides. This
      overview is based on published literature and unpublished data from the authors.
      In particular, glutathione conjugates and their biotransformation products are
      discussed in detail. In addition, the fragmentation of the major classes of
      conjugates, i.e. glucuronides, glucosides, malonylglucosides, sulfates, acetates,
      methyl and glycine conjugates, is reported. Collision-induced dissociation, as
      studied by tandem mass spectrometry, allows the rapid identification of the type
      of conjugate, whereas the exact conjugation site can in general be determined
      only by additional NMR experiments.

PMID- 15844511
TI  - Proteomic LC-MS systems using nanoscale liquid chromatography with tandem mass
      spectrometry.
AB  - Current nano-scale liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS)
      approaches in proteome research are reviewed from an analytical perspective. For
      comprehensive analysis of cellular proteins, analytical methods with higher
      resolution, sensitivity, and wider dynamic range are required. Miniaturized LC
      coupled with tandem mass spectrometry is currently one of the most versatile
      techniques. In this review, the current status of nanoLC-MS/MS systems as well as
      data management systems is addressed. In addition, the future prospects for
      complete proteomics are discussed.

PMID- 15844512
TI  - Quantitative determination of four nitrofuran metabolites in meat by isotope
      dilution liquid chromatography-electrospray ionisation-tandem mass spectrometry.
AB  - A confirmatory method based on isotope dilution liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) has been developed for the low-level determination of
      residues of four nitrofuran veterinary drugs in meat, e.g., furazolidone,
      furaltadone, nitrofurantoin, and nitrofurazone. The procedure entails an acid
      catalysed release of protein-bound metabolites, followed by their in situ
      conversion into the 2-nitrobenzaldehyde (NBA) imine-type derivatives. Liquid
      liquid extraction and clean-up on a polymeric solid phase extraction cartridge
      are then performed before LC-MS/MS analysis by positive electrospray ionisation
      (ESI) applying multiple reaction monitoring of three transition reactions for
      each compound. Reliable quantitation is obtained by using one deuterated analogue
      per analyte (d4-NBA derivative) as internal standard (IS). Validation of the
      method in chicken meat was conducted following the European Union (EU) criteria
      for the analysis of veterinary drug residues in foods. The decision limits
      (CCalpha) were 0.11-0.21 microg/kg, and the detection capabilities (CCbeta) 0.19
      0.36 microg/kg, thus below the minimum required performance limit (MRPL) set at 1
      microg/kg by the EU. The method is robust and suitable for routine quality
      control operations, and more than 200 sample injections were performed without
      excessive pollution of the mass spectrometer or loss of LC column performance.

PMID- 15844513
TI  - Simple confirmatory assay for analyzing residues of aminoglycoside antibiotics in
      bovine milk: hot water extraction followed by liquid chromatography-tandem mass
      spectrometry.
AB  - A simple, selective and sensitive procedure for determining nine widely used
      aminoglycoside antibiotics (AGs) in bovine whole milk is presented. It is based
      on matrix solid-phase dispersion with heated water, at 70 degrees C, as
      extractant followed by liquid chromatography (LC)-tandem mass spectrometry (MS)
      using an electrospray ion source. After acidification and filtration, 0.2 ml of
      the aqueous extract was injected into the LC column. MS data acquisition was
      performed in the multi reaction monitoring mode, selecting two (three, when
      possible) precursor ion > product ion transitions for each target compound.
      Analyte recoveries ranged between 70 and 92%. Using aminosidine (an AG not used
      in veterinary medicine) as surrogate internal standard, the accuracy of the
      method at three spike levels varied between 80 and 107% with R.S.D. not larger
      than 11%. The limits of quantification were between 2 ng/ml (apramycin) and 13
      ng/ml (streptomycin). They are well below the tolerance levels set by both the
      European Union and the U.S. Food and Drug Administration.

PMID- 15844514
TI  - Determination of the sum of malachite green and leucomalachite green in salmon
      muscle by liquid chromatography-atmospheric pressure chemical ionisation-mass
      spectrometry.
AB  - A sensitive method for the determination and confirmation of the sum of malachite
      green (MG) and leucomalachite green (LMG) in salmon muscle has been developed. It
      is based on the use of an oxidative pre-column reaction which converts LMG into
      MG previous to liquid chromatography-atmospheric pressure chemical ionisation
      mass spectrometry (LC-APCI-MS) analysis. The determination of both compounds
      together constitutes a good screening method to confirm the presence of this kind
      of residue, taking into account that the combined signals will provide a gain of
      sensitivity. The detection limit, determined for spiked salmon samples using the
      confirmatory ion m/z 313, was 0.15 microg/kg. The recoveries determined at a
      spiking level of 2 microg/kg were 85 and 70% for LMG and MG, respectively, with
      respective relative standard deviations of 1.3 and 3.1%.

PMID- 15844515
TI  - Determination of kava lactones in food supplements by liquid chromatography
      atmospheric pressure chemical ionisation tandem mass spectrometry.
AB  - Reversed-phase liquid chromatography and detection with atmospheric pressure
      chemical ionisation tandem mass spectrometry was used for the determination of
      kava extracts in herbal mixtures. One percent of kava extract can be detected,
      corresponding to approximately 0.05-0.2 mg/g of the individual kava lactones
      kavain, dihydrokavain, yangonin, desmethoxyyangonin, methysticin and
      dihydromethysticin. Reliable quantification is obtained from concentrations of
      0.25-1 mg/g, depending on the compound. At these concentration levels, the
      relative standard deviations were 10-14%. Validation showed good linearity and
      recoveries for all the kava lactones with the exception of yangonin. During
      method development, degradation of yangonin was observed. The degradation product
      was identified by nuclear magnetic resonance (NMR) as cis-yangonin. The method
      was applied to the analysis of commercial herbal products available in the Dutch
      market before and after market restrictions of kava-containing preparations. The
      results showed that even though 'old' products contained kava extract, the new
      formulations were negative on kava lactones. cis-Yangonin was also present in the
      herbal products.

PMID- 15844516
TI  - Comparison of liquid chromatography using triple quadrupole and quadrupole ion
      trap mass analyzers to determine pesticide residues in oranges.
AB  - Liquid chromatography-triple quadrupole/mass spectrometry (LC-TQ/MS) and liquid
      chromatography-quadrupole ion trap/mass spectrometry (LC-QIT/MS) for determining
      bupirimate, hexaflumuron, tebufenpyrad, buprofezin, pyriproxyfen, and fluvalinate
      in fruits have been compared. The differences in the mass spectra obtained by
      triple and ion trap quadrupoles are discussed, showing how both of them provide
      interesting features. The evaluation of the two instruments was carried out by
      ethyl acetate extraction of oranges spiked with the studied pesticides at LOQ and
      10 times the LOQ. Results obtained by LC-TQ/MS correlated well with those
      obtained by LC-QIT/MS. Recoveries were 70-94% by LC-TQ/MS and 72-92% by LC-QIT/MS
      with the R.S.D. from five replicate analysis 4-14% and 8-18%, respectively.
      Matrix effects were tested for both techniques by standard addition to blank
      extracts. Although the matrix effects are not originated in mass analyzer but in
      the LC/MS interface, they were, generally, more marked by LC-QIT-MS than by LC
      TQ/MS. The limits of quantification (LOQs) were 0.005-0.2 mg kg(-1) by both
      equipments--appropriate values for determining these pesticides in orange from
      the regulatory point of view. The results indicate that the TQ provides higher
      precision, better linearity, it is more robust, and when the purpose of the
      analysis is quantitative determination, preferable over the QIT. However, the
      application of both mass spectrometers to analyze orange samples conventionally
      treated showed that any can be used for qualitative and quantitative purposes.

PMID- 15844517
TI  - Matching unknown empirical formulas to chemical structure using LC/MS TOF
      accurate mass and database searching: example of unknown pesticides on tomato
      skins.
AB  - Traditionally, the screening of unknown pesticides in food has been accomplished
      by GC/MS methods using conventional library searching routines. However, many of
      the new polar and thermally labile pesticides and their degradates are more
      readily and easily analyzed by LC/MS methods and no searchable libraries
      currently exist (with the exception of some user libraries, which are limited).
      Therefore, there is a need for LC/MS approaches to detect unknown non-target
      pesticides in food. This report develops an identification scheme using a
      combination of LC/MS time-of-flight (accurate mass) and LC/MS ion trap MS (MS/MS)
      with searching of empirical formulas generated through accurate mass and a
      ChemIndex database or Merck Index database. The approach is different than
      conventional library searching of fragment ions. The concept here consists of
      four parts. First is the initial detection of a possible unknown pesticide in
      actual market-place vegetable extracts (tomato skins) using accurate mass and
      generating empirical formulas. Second is searching either the Merck Index
      database on CD (10,000 compounds) or the ChemIndex (77,000 compounds) for
      possible structures. Third is MS/MS of the unknown pesticide in the tomato-skin
      extract followed by fragment ion identification using chemical drawing software
      and comparison with accurate-mass ion fragments. Fourth is the verification with
      authentic standards, if available. Three examples of unknown, non-target
      pesticides are shown using a tomato-skin extract from an actual market place
      sample. Limitations of the approach are discussed including the use of A + 2
      isotope signatures, extended databases, lack of authentic standards, and natural
      product unknowns in food extracts.

PMID- 15844518
TI  - Capillary liquid chromatography-microcoil 1H nuclear magnetic resonance
      spectroscopy and liquid chromatography-ion trap mass spectrometry for on-line
      structure elucidation of isoflavones in Radix astragali.
AB  - Miniaturization and hyphenation of chromatographic separation techniques to
      nuclear magnetic resonance spectroscopy is being increasingly demanded in the
      field of biomedical, drug metabolite and natural product analysis. Herein,
      capillary liquid chromatography was coupled on-line to microcoil 1H nuclear
      magnetic resonance spectroscopy (capLC-NMR) equipped with a 1.5 microL solenoidal
      probe for structure elucidation of isoflavones in Radix astragali. The extract
      was screened by HPLC-UV-MS as the preliminary step and four major peaks were
      identified tentatively by ion trap mass spectrometry molecular weights and
      characteristic fragments. Then, stopped-flow capLC-UV-NMR was performed using 33
      microg extract injected on-column. The four peaks were parked manually in the
      micro probe one by one and corresponding 1H NMR spectra were recorded with good
      resolutions under the applied capLC-NMR conditions (120 and 220 ng injected on
      column for peaks 2 and 4, respectively). All aromatic regions of 1H NMR spectra
      correlated well to the characteristic signals of isoflavone aglycone protons. And
      the signal corresponding to the anomeric proton of the glucopyranoside of
      isoflavone glycoside was also obtained for peak 1. Therefore, these four peaks
      are determined as calycosin-7-O-beta-D-glucopyranoside (1), ononin (2), calycosin
      (3) and formononetin (4) unambiguously. The capLC-NMR results indicate that this
      hyphenated technique could be used for the determination of a great variety of
      natural products from small sample amounts, e.g., only 5 g R. astragali in this
      study.

PMID- 15844519
TI  - Isotope tag method for quantitative analysis of carbohydrates by liquid
      chromatography-mass spectrometry.
AB  - We have previously demonstrated that liquid chromatography/mass spectrometry
      equipped with a graphitized carbon column (GCC-LC/MS) is useful for the
      structural analysis of carbohydrates in a glycoprotein. Here, we studied the
      monosaccharide composition analysis and quantitative oligosaccharide profiling by
      GCC-LC/MS. Monosaccharides were labeled with 2-aminopyridine and then separated
      and monitored by GCC-LC/MS in the selective ion mode. The use of tetradeuterium
      labeled pyridylamino (d4-PA) monosaccharides as internal standards, which were
      prepared by the tagging of standard monosaccharides with hexadeuterium-labeled 2
      aminopyridine (d6-AP), afforded a good linearity and reproducibility in ESIMS
      analysis. This method was successfully applied to the monosaccharide composition
      analysis of model glycoproteins, fetuin, and erythropoietin. For quantitative
      oligosaccharide profiling, oligosaccharides released from an analyte and a
      standard glycoprotein were tagged with d0- and d6-AP, respectively, and an equal
      amount of d0- and d4-PA oligosaccharides were coinjected into GCC-LC/MS. In this
      procedure, the oligosaccharides that existed in either analyte or a standard
      glycoprotein appeared as single ions, and the oligosaccharides that existed in
      both analyte and a standard glycoprotein were detected as paired ions. The
      relative amount of analyte oligosaccharides could be determined on the basis of
      the analyte/internal standard ion-pair intensity ratio. The quantitative
      oligosaccharide profiling enabled us to make a quantitative and qualitative
      comparison of glycosylation between the analyte and standard glycoproteins. The
      isotope tag method can be applicable for quality control and comparability
      assessment of glycoprotein products as well as the analysis of glycan alteration
      in some diseases.

PMID- 15844520
TI  - Operational options to reduce matrix effects in liquid chromatography
      electrospray ionization-mass spectrometry analysis of aqueous environmental
      samples.
AB  - Matrix effects like signal enhancement or suppression can severely compromise
      quantitative analysis of environmental samples with liquid chromatography
      electrospray ionization-mass spectrometry (LC-ESI-MS). Several operational
      options were studied to reduce such matrix effects in the determination of polar
      organic trace contaminants from water, like non-steroidal anti-inflammatory
      drugs, among them ibuprofen, diclofenac and naproxen, lipid regulators like
      bezafibrate and clofibric acid and industrial chemicals (2-substituted
      benzothiazoles). A step-wise removal of organic matrix from a wastewater sample
      by ultrafiltration showed that the majority of matrix effects in that sample was
      due to low molecular weight compounds <1 kDa. For such wastewaters samples size
      exclusion, as in restricted access material (RAM), is not a useful clean-up
      strategy. Reducing the eluent flow entering the ESI interface by post-column
      splitting increased instrumental sensitivity and reduced matrix effects. The flow
      optimum was analyte-dependent and ranged from 20 to 100 microL/min. Sensitivity
      in the positive ion mode increased up to nine-fold upon flow-reduction for some
      analytes detected in the positive ion mode. At low flow rates matrix effects are
      reduced by 45-60% on average. If moderate matrix effects occurred, post-column
      splitting may allow obtaining reliable quantitative data even with external
      calibration.

PMID- 15844521
TI  - Determination of non-ionic polyethoxylated surfactants in wastewater and river
      water by mixed hemimicelle extraction and liquid chromatography-ion trap mass
      spectrometry.
AB  - The capability of hemimicelles-based solid phase extraction (SPE)/liquid
      chromatography/atmospheric pressure chemical ionisation in positive mode, ion
      trap mass spectrometry (LC/(APCl+-IT)-MS) for the concentration, separation and
      quantitation of non-ionic surfactants has been investigated. Concentration was
      based on the formation of mixed aggregates of analytes [alkylphenol ethoxylates
      (APE, octyl and nonyl) and alkyl ethoxylates (AE, C12-C16)] with the anionic
      surfactant sodium dodecyl sulphate (SDS) that is adsorbed on alumina. Parameters
      affecting SPE were investigated on the basis that hemimicelles are dynamic
      entities in equilibrium with the aqueous phase. The performance of ion trap mass
      spectrometry for MS and MS/MS quantitation of non-ionic homologues was assessed.
      Recoveries of analytes from wastewater influent and effluent and river water
      samples ranged between 91 and 98% and were found independent on the length of the
      alkyl chain under the optimised conditions. Anionic surfactants did not interfere
      to the levels found in environmental samples. The detection limits ranged between
      14 and 111 ng/l for wastewater influent, 10 and 40 for wastewater effluent and 4
      and 35 for river water, after concentration of 250, 500 and 750 ml of sample,
      respectively. The approach was applied to the determination of AE and APE in
      influent and effluent samples from four wastewater treatment plants and four
      river samples. The concentrations of individual non-ionic surfactants found
      ranged between 0.3 and 373 microg/l.

PMID- 15844522
TI  - Application of liquid chromatography-electrospray-tandem mass spectrometry for
      the identification and characterisation of linear alkylbenzene sulfonates and
      sulfophenyl carboxylates in sludge-amended soils.
AB  - A novel procedure was developed for the simultaneous determination of linear
      alkylbenzene sulfonates (LAS) and their major metabolites, sulfophenyl
      carboxylates (SPC), in sludge-amended soil. After pressurised liquid extraction
      with methanol/water (90:10) and a clean-up on C18 solid-phase extraction
      cartridges, final analysis was done by ion-pair liquid chromatography
      electrospray-tandem mass spectrometry (LC-ESI-MS/MS). With this method, SPC with
      5-13 carbon atoms in the aliphatic side chain were identified for the first time
      in agricultural soils treated with sewage sludge. Quantification of LAS and SPC
      in soil from 10 field sites, which differed in the history of sludge application,
      gave total concentrations of 120-2840 microg kg(-1) for LAS and of 4-220 microg
      kg(-1) for SPC. The data provided evidence for rapid biodegradation of LAS in the
      initial phase after sludge amendment with a transitory build-up of high
      concentrations of, mainly, short-chain SPC. Trace amounts of residual LAS and SPC
      were detected in soils having received the last sludge treatment 10 days to 4
      years prior to sampling.

PMID- 15844523
TI  - Enhanced sensitivity for the determination of ambiphilic polyaromatic amines by
      LC-MS/MS after acetylation.
AB  - A new method for the analysis of aminonitropyrenes and diaminopyrenes was
      developed for urine and hemoglobin samples using LC-MS/MS. A good separation by
      LC was only achieved after derivatization of the amino group, which also
      increased sensitivity to a limit of detection (LOD) of 0.1 pg (on column) for
      diaminopyrene and 5 pg for aminonitropyrene using electrospray ionization (ESI).
      Compared to a derivatization with pentafluorobenzoyl chloride yielding only one
      sensitive MS/MS transition, acetylation offers the advantages of a higher
      selectivity with two sensitive MS/MS transitions and the possibility of a direct
      detection of acetylated aminonitropyrenes and diaminopyrenes formed metabolically
      in vivo. Acetylated diaminopyrene was detected in urine and after hydrolysis of
      the corresponding hemoglobin adducts followed by acetylation in blood samples of
      rats after administration of dinitropyrene but not in controls. A method based on
      GC-MS with negative chemical ionization of the electrophore labelled metabolites
      was non-selective since only one major ion [M - HF]- was formed and some isobaric
      peaks were observed preventing unequivocal analyte identification at
      concentrations close to the LOD.

PMID- 15844524
TI  - Ion chromatography-electrospray mass spectrometry for the identification of low
      molecular-weight organic acids during the 2,4-dichlorophenol degradation.
AB  - End-product identification of organic pollutants during oxidation water
      treatments is of environmental concern due to their potential toxicity. In this
      work the coupling of ion chromatography (IC), equipped with a membrane ion
      suppressor, and electrospray ionization mass spectrometry (ESI-MS) has been
      successfully exploited for the identification of novel low molecular weight
      organic acids formed as final by-products of 2,4-dichloro-phenol (DCP)
      degradation by Fenton's reagent, an oxidation method widely employed to degrade
      recalcitrant organic pollutants in industrial wastewater. The IC-ESI-MS
      analytical set-up not only allowed the detection of known organic acids but also
      the identification of 13 new low molecular weight organic acids as a result of
      extensive oxidation of the parent organic pollutant. Some of the novel organic
      acids were shown to be chlorine containing by-products and, consequently, of
      environmental concern. The analytical set-up could be used for characterizing the
      unknown organic carbon fraction arising from oxidation water treatments.

PMID- 15844525
TI  - Approaches for coupling solid-phase microextraction to nanospray.
AB  - Biocompatible solid-phase microextraction (SPME) devices were prepared using two
      restricted access materials (RAM) as the SPME coating. The restricted access
      materials were immobilized on steel and platinum wires. The selective coating
      eliminated most of the matrix interference, which allowed the coupling to mass
      spectrometry without further purification. The SPME devices were interfaced to
      mass spectrometry by electronanospray. Several experimental set-ups are described
      and discussed herein. For the in situ extraction of peptides from the tryptic
      digests, trypsin was immobilized both on steel wires and on the inside wall of a
      vial. The devices were incubated together with the RAM-SPME devices and a protein
      (casein) solution. After the protein digestion, the resulting peptides were
      analyzed by SPME/nanospray. The vial approach provided the best results; up to
      eight peptides could be identified which corresponds to a sequence coverage of
      58%. The limit of detection of SPME/nanospray for the extraction of peptides from
      an aqueous solution was about 50 fmol/mL. The results demonstrate that the direct
      coupling of SPME to nanospray can reduce analysis time and is an attractive
      alternative to conventional approaches like Zip-Tip purification.

PMID- 15844526
TI  - A new LC/APCI-MS method for the determination of cholesterol oxidation products
      in food.
AB  - Cholesterol oxidation products (COPs) can be formed in the body or in animal
      foods from cholesterol during food processing. A new method for the extraction
      and quantification of cholesterol, 7-ketocholesterol, cholestane-3beta-5alpha
      6beta-triol, 25-hydroxycholesterol, 5,6alpha-epoxycholesterol, and 7beta
      hydroxycholesterol by means of reversed-phase LC/atmospheric pressure chemical
      ionization mass spectrometry is presented. A baseline separation of all COPs was
      achieved, allowing a separate quantification also for isobaric compounds. The
      limits of detection were 15-30 ng/mL, quantification was performed from 100 ng/mL
      to 10 microg/mL with RSD < 2%. The method was applied successfully to the
      determination of cholesterol and COPs in processed foods such as pork, beef,
      chicken, and egg.

PMID- 15844527
TI  - Determination of pharmaceuticals, iodinated contrast media and musk fragrances in
      sludge by LC/tandem MS and GC/MS.
AB  - Analytical methods have been developed that allow for the determination of
      antiphlogistics, lipid regulators, the antiepileptic carbamazepine, cytostatic
      agents, the psychiatric drug diazepam and iodinated contrast media (ICM) as well
      as two major polycyclic musk fragrances HHCB (galaxolide) and AHTN (tonalide) in
      activated and digested sludge. The procedures consist of ultrasonic solvent
      extraction (USE) using methanol/acetone or pressurized liquid extraction (PLE)
      using 100% methanol. Clean-up was performed with C18ec material and silica gel
      followed by LC tandem MS (electrospray or atmospheric pressure chemical
      ionization) detection for pharmaceuticals and iodinated contrast media as well as
      GC/MS in the SIM mode for musk fragrances. Absolute recoveries from spiked
      activated sludge in general ranged from 88+/-4 to 119+/-20% for ICM and were 78+/
      15 and 87+/-10% for the AHTN and HHCB, respectively. For the pharmaceuticals,
      absolute recoveries in activated sludge ranged between 43 and 78%. Subsequently,
      compensation of losses was carried out by using surrogate standards (acidic
      pharmaceuticals: fenoprop, neutral pharmaceuticals: dihydro-carbamazepine, musk
      fragrances: AHTN-D3). With one exception the recoveries were also adequate in
      digested sludge ranging from 43% to 120%.

PMID- 15844528
TI  - Determination of chloroacetanilides, triazines and phenylureas and some of their
      metabolites in soils by pressurised liquid extraction, GC-MS/MS, LC-MS and LC
      MS/MS.
AB  - Pressurised liquid extraction (PLE) technique was used for the simultaneous
      extraction of phenylureas, triazines and chloroacetanilides and some of their
      metabolites from soils. Extractions were performed by mixing 15 g of dried soil
      with 30 mL of acetone under 100 atm at 50 degrees C, during 3 min and with three
      PLE cycles. Prior to the analysis of naturally contaminated soils, each of the
      five representative soil matrices used as blanks (of different depths) was spiked
      in triplicate with standards of each parent and degradation compound at about 10,
      30 and 120 microg/kg. For each experiment, isoproturon-D6 and atrazine-D5 were
      used as surrogates. Analysis of phenylureas and metabolites of triazines and
      phenylureas was carried out by reversed phase liquid chromatography/mass
      spectrometry (LC-MS) and LC-MS/MS in the positive mode. Gas chromatography
      (GC)/ion trap mass spectrometry was used in the MS/MS mode for the parent
      triazines and chloroacetanilides. The average extraction recoveries were above
      85%, except for didesmethyl-isoproturon, and quantification limits were between
      0.5 and 5 microg/kg. The optimised multi-residue method was applied to soils and
      solids below the root zone, sampled from agricultural plots of a small French
      hydrogeological basin.

PMID- 15844529
TI  - Comprehensive two-dimensional gas chromatography in combination with rapid
      scanning quadrupole mass spectrometry in perfume analysis.
AB  - Single column gas chromatography (GC) in combination with a flame ionization
      detector (FID) and/or a mass spectrometer is routinely employed in the
      determination of perfume profiles. The latter are to be considered medium to
      highly complex matrices and, as such, can only be partially separated even on
      long capillaries. Inevitably, several monodimensional peaks are the result of two
      or more overlapping components, often hindering reliable identification and
      quantitation. The present investigation is based on the use of a comprehensive GC
      (GC x GC) method, in vacuum outlet conditions, for the near to complete
      resolution of a complex perfume sample. A rapid scanning quadrupole mass
      spectrometry (qMS) system, employed for the assignment of GC x GC peaks, supplied
      high quality mass spectra. The validity of the three-dimensional (3D) GC x GC-qMS
      application was measured and compared to that of GC-qMS analysis on the same
      matrix. Peak identification, in all applications, was achieved through MS spectra
      library matching and the interactive use of linear retention indices (LRI).

PMID- 15844530
TI  - Comprehensive two-dimensional gas chromatography coupled to a rapid-scanning
      quadrupole mass spectrometer: principles and applications.
AB  - The principles, practicability and potential of comprehensive two-dimensional
      (2D) gas chromatography coupled to a rapid-scanning quadrupole mass spectrometer
      (GC x GC-qMS) for the analysis of complex flavour mixtures in food, allergens in
      fragrances and polychlorinated biphenyls (PCBs) were studied. With a scan speed
      of 10,000 amu/s, monitoring over a mass range of up to 200 atomic mass unit (amu)
      can be achieved at an acquisition frequency of 33 Hz. Extending this mass range
      and/or increasing the data acquisition frequency results in a loss of spectral
      quality. Optimal parameter settings allow, next to unambiguous
      identification/confirmation of target compounds on the basis of high-quality mass
      spectra, fully satisfactory quantification (three to four modulations per peak)
      with linear calibration plots and detection limits in the low-pg level. The
      potential of time-scheduled data acquisition to increase the effective mass range
      within one GC x GC run was also explored. The analyses, with baseline separation
      of the flavours, allergens and PCB target compounds, took less than 30 min.

PMID- 15844531
TI  - Quadrupole mass spectrometer operating in the electron-capture negative ion mode
      as detector for comprehensive two-dimensional gas chromatography.
AB  - A recently introduced rapid-scanning quadrupole mass spectrometer (qMS) with an
      electron-capture negative ion (ECNI) option, the Perkin-Elmer Clarus 500, was
      tested as a detector for comprehensive two-dimensional gas chromatography (GC x
      GC). The parameters influencing the data acquisition rate in the scan mode, such
      as scan time and inter-scan delay, and in the selected ion monitoring mode, such
      as dwell time and inter-channel delay, were evaluated. In the scan mode, good
      quality mass spectra covering a range of 300 Da can be obtained at an acquisition
      rate of 23 Hz; in selected ion monitoring, an acquisition rate of 90Hz can be
      achieved when monitoring a single ion. Compared with electron ionisation, the use
      of electron-capture negative ionisation causes no extra peak broadening. As
      applications, mixtures of polychlorinated n-alkanes (PCAs), polybrominated
      diphenyl ethers (PBDEs) and polychlorinated dibenzo-p-dioxins (PCDDs) and
      dibenzofurans (PCDFs) were analysed. The separation of PCAs based on their number
      of chlorine substituents was confirmed for the first time by using GC x GC-ECNI
      qMS in the scan mode and a significantly improved limit of detection was achieved
      for BDEs (10-150 fg injected) and CDD/Fs (10-700 fg injected) in the selected ion
      monitoring mode.

PMID- 15844532
TI  - Recent advances in mass spectrometric measurement of dioxins.
AB  - Past years, many efforts have been dedicated to the development of alternative
      analytical methods for the measurement of dioxins in various types of matrices.
      Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs),
      and polychlorinated biphenyls (PCBs) are compounds that are present in samples at
      part-per-billion (ppb) or part-per-trillion (ppt) level. Their measurement
      requires the use of very sensitive analytical methods. Gas chromatography (GC)
      coupled to quadrupole ion storage mass spectrometry (QISTMS), fast GC (FGC)
      coupled to time-of-flight mass spectrometry (TOFMS) and comprehensive two
      dimensional gas chromatography (GC x GC) coupled to TOFMS are the more promising
      tools challenging the reference GC high resolution mass spectrometry (HRMS) based
      on sector instruments. We report herein some of the advances we achieved in the
      past years in our laboratory on the development of alternative measurement
      methods for those compounds.

PMID- 15844533
TI  - Characterization and pattern recognition of oil-sand naphthenic acids using
      comprehensive two-dimensional gas chromatography/time-of-flight mass
      spectrometry.
AB  - Oil-sand naphthenic acids (NAs) are organic wastes produced during the oil-sand
      digestion and extraction processes and are very difficult to separate and analyze
      as individual components due to their complex compositions. A comprehensive two
      dimensional gas chromatography/time of flight mass spectrometry (GC x GC/TOF-MS)
      system was applied for the characterization of two commercial mixtures of
      naphthenic acids (Fluka and Acros) and a naphthenic acid sample extracted from
      the Syncrude tailings. Contour plots of chromatographic distributions of
      different Z homologous series of the Fluka, Acros and Syncrude NAs were
      constructed using fragment ions that were characteristic of the NA's molecular
      structures. Well-ordered patterns were observed for NAs of Z= 0 and -2 which
      corresponded to acyclic acids and monocyclic acids, respectively. For NAs of Z= 
      4, -6, and -8, specific zones were observed which would allow the pattern
      recognition of these NAs obtained from different origins. As expected, gas
      chromatographic retention times increase with the number of the carbons and the
      number of rings in the molecules. Little signal was obtained for NAs with Z
      numbers of -10, or lower. Deconvoluted mass spectra of various NA isomers were
      derived from the reconstructed GC x GC chromatogram, permitting detailed
      structural elucidations for NAs in the future. The current study demonstrated
      that the combination of GC x GC and the TOF-MS is a powerful to identify origins
      of the NAs in an effective manner. GC x GC/TOF-MS alone, however, may not be
      enough to characterize each individual isomer in a complex mixture such as NAs.
      The use of mass deconvolution software followed by library search have thus
      become necessary to separate and study the mass spectrum of each individual NA
      component, allowing a detailed identification of the toxic components within the
      NAs mixture.

PMID- 15844534
TI  - Towards smaller and faster gas chromatography-mass spectrometry systems for field
      chemical detection.
AB  - Gas chromatography-mass spectrometry (GC-MS) is already an important laboratory
      method, but new sampling techniques and column heating approaches will expand and
      improve its usefulness for detection and identification of unknown chemicals in
      field settings. In order to demonstrate commercially-available technical advances
      for both sampling and column heating, we used solid phase microextraction (SPME)
      sampling of both water and air systems, followed by immediate analysis with a
      resistively heated analytical column and mass spectrometric detection. High
      concern compounds ranging from 140 to 466 amu were analyzed to show the
      applicability of these techniques to emergency situations impacting public
      health. A field portable (about 35 kg) GC-MS system was used for analysis of
      water samples with a resistively heated analytical column externally mounted as a
      retrofit using the air bath oven of the original instrument design to heat
      transfer lines. The system used to analyze air samples included a laboratory mass
      spectrometer with a dedicated resistive column heating arrangement (no legacy air
      bath column oven). The combined sampling and analysis time was less than 10 min
      for both air and water sample types. By combining dedicated resistive column
      heating with smaller mass spectrometry systems designed specificallyfor use in
      the field, substantially smaller high performance field-portable instrumentation
      will be possible.

PMID- 15844535
TI  - Evaluation of four mass spectrometric methods for the gas chromatographic
      analysis of polychlorinated n-alkanes.
AB  - The suitability of four mass spectrometric methods for the gas chromatographic
      analysis of polychlorinated n-alkanes (PCAs, also called chlorinated paraffins)
      was evaluated and compared using spiked and fish liver samples. Electron
      ionization tandem mass spectrometry (EI-MS/MS) as well as electron capture
      negative ionization (ECNI) combined with low and high resolution mass
      spectrometry and CH4/CH2Cl2-negative ion chemical ionization (NICI) low
      resolution mass spectrometry were investigated. All methods showed an accuracy of
      <21% for the analysis of spiked fish samples. However, the analysis of real
      samples showed deviations of up to 46% between the four mass spectrometric
      methods. The influence of the selected reference standard on quantification was
      also evaluated. The use of a quantification standard with a degree of
      chlorination deviating from that of the sample can result in differences of >
      100% for the ECNI methods. EI-MS/MS and CH4/CH2Cl2-NICI led to errors of maximum
      17% and 33%, respectively, independent from the degree of chlorination of the
      used reference standard.

PMID- 15844536
TI  - Simultaneous determination of anabolic steroids and synthetic hormones in meat by
      freezing-lipid filtration, solid-phase extraction and gas chromatography-mass
      spectrometry.
AB  - Estradiol, testosterone, progesterone, zeranol and diethylstilbestrol including
      estradiol metabolites were determined simultaneously in meat. Extraction of
      growth hormones was carried out by ultasonication using a methanol-water mixture.
      The growth hormones in the meat extract can be effectively separated from lipids
      by freezing-lipid filtration, followed by C8-solid phase extraction (SPE). During
      freezing-lipid filtration, about 90% of lipids are removed without any
      significant loss of growth hormones. For further clean-up, silica- and
      aminopropyl-SPE were used. To enhance detection sensitivity, the growth hormones
      are derivatized with trimethylsilyl reagents. Quantitation using isotope-labelled
      internal standards was performed by gas chromatography-mass spectrometry in the
      selected ion monitoring mode. The method detection limits were 0.1-0.4 microg/kg
      for all growth hormones. Overall recoveries of synthetic and natural growth
      hormones were 68-106% with coefficients of variation of 5-16% for the complete
      procedure.

PMID- 15844537
TI  - Partial elucidation of Trichogramma putative sex pheromone at trace levels by
      solid-phase microextraction and gas chromatography-mass spectrometry studies.
AB  - Virgin females of the minute parasitoid wasp Trichogramma turkestanica produce
      about 2 pg/h of two putative sex pheromonal compounds. These compounds could be
      successfully sampled during 20-50 h with SPME from 1.8 mL vials, containing 50
      110 wasps and analysed by GC-MS. Accurate mass measurements at the 1 ng scale
      were possible with an internal standard of sulphur. One compound with MW 236 was
      identified as a C17H32 hydrocarbon while the other compound was the corresponding
      allylic alcohol with composition C17H32O. The alcohol could be silylated on-fibre
      and its mass spectrum suggested the presence of a conjugated 2,4-diene moiety. A
      miniaturised solvent extraction system for SPME needles, using 5 microL of
      acetone in a microtube was developed. After reaction of the extracted volatiles
      with the dienophile 4-methyl-1,2,4-triazoline-3,5-dione (MTAD), GC-MS of the MTAD
      adducts confirmed the presence of a diene. Interpretation of the combined mass
      spectral data, in combination with retention indexes of both compounds on non
      polar and polar columns, suggested 2,6,8,12-tetramethyltrideca-2,4-diene and
      2,6,8,12-tetramethyltrideca-2,4-dien-1-ol as most probable structures. These
      compounds have not been described previously. Biogenetically, they are most
      likely polyketides made up of a C4 starter unit that has been elongated with C2
      and C3 units. Further biological and synthetic studies are necessary to prove
      their role as sex pheromone, confirm the proposed structures and determine the
      correct stereochemistry of the double bonds and the methyl groups.

PMID- 15844538
TI  - Investigation of the feeding effect on the 13C/12C isotope ratio of the hormones
      in bovine urine using gas chromatography/combustion isotope ratio mass
      spectrometry.
AB  - The effect of the feeding on the 13C/12C isotope ratio of four endogenous steroid
      hormones testosterone (T), epi-testosterone (epi-T), dehydroepiandrosterone
      (DHEA) and etiocholanolone (ETIO) in bovine urine was investigated. An analytical
      method to determine the accurate isotope ratio was developed including an
      extensive clean up followed by enrichment of the analytes in two steps of HPLC
      fractionation. Feeding experiments with four young animals were performed using
      C3 and C4 plants (grass, maize silage, hay, etc.) over a time period of about 280
      days. One cattle was used as a control animal with no change of its diet over the
      full period. The detection of the 13C/12C isotope ratio of the acetylated
      extracts was performed by gas chromatography/combustion isotope ratio mass
      spectrometry. After the first change of the feeding from C4 to C3 plants
      significant changes of the delta 13C % values were observed from the -19 to -23%
      level to the -24 to -32% level for etiocholanolone and epi-testosterone in urine
      of three animals, whereas the DHEA values remained under the level of the two
      metabolites. Testosterone could not be detected with GC-C-IRMS due to its low
      concentration in young animals. After the second change of the diet from C3 to C4
      plants (after 222 days), the measured delta 13C % values have been stabilised at
      the original level. The results show that in case of the feeding with only C3
      plants the endogenous delta values of -32% can be reached. In this case the
      contribution of exogenous material with a delta value of -32% could not be
      detected independently of the concentration. If the diet contains C4 plants the
      difference or the ratio of the delta 13C % values becomes the determinant in the
      discriminatory power. For validation of the method a human and a cattle were
      treated with testosterone and the delta 13C % values were measured in incurred
      human and cattle urine.

PMID- 15844539
TI  - Use of solid-phase microextraction for the detection of acetic acid by ion-trap
      gas chromatography-mass spectrometry and application to indoor levels in museums.
AB  - A simple and efficient method using solid-phase microextraction (SPME) and gas
      chromatography-ion trap mass spectrometry (GC-ITMS) was developed for the
      analysis of acetic acid in air. The choice of the SPME fibre revealed to be
      critical as well as the sampling and desorption time. A dilution vessel was used
      for calibration. The precision of the method was found to be 4.7% relative
      standard deviation (RSD) and the detection limit 5.7 microg m(-3). The SPME-GC-MS
      technique was applied to the analysis of acetic acid in museum atmospheres.

PMID- 15844540
TI  - Unusual collision-induced dissociation of fluorated and non-fluorated alpha
      nitrotoluene analogs in a gas chromatograph triple-stage quadrupole mass
      spectrometer under electron-capturing negative-ion chemical ionization
      conditions.
AB  - Unusual collision-induced dissociation (CID) of perfluorated and non-perfluorated
      alpha-nitrotoluene analogs in a gas chromatograph triple-stage quadrupole (TSQ)
      mass spectrometer (GC-QqQ-MS) under electron-capturing negative-ion chemical
      ionization conditions is reported. CID of [M - 1]- of alpha-nitro-2,3,4,5,6
      pentafluorotoluene (C6F5CH2-NO2) and alpha-nitro-2,5-difluorotoluene (C6H3F2CH2
      NO2) produced an intense ion with m/z 66. By using 15N- or 18O-labelled C6F5CH2
      NO2 analogs, we found that this anion has the formula C3NO. By contrast, CID of
      [M - 1]- of alpha-nitrotoluene (C6H5CH2-NO2) and alpha-nitro-3,5-difluorotoluene
      (C6H3F2CH2-NO2) produced an anion with m/z 86 with the formula C3H4NO2. The
      expected CID of the C-N-bond of all alpha-nitrotoluene analogs to form the
      nitrite anion (NO2-, m/z 46) did not occur. We propose mechanisms for the
      formation of the anions C3NO and C3H4NO2 in the collision chamber of the TSQ mass
      spectrometer. The most likely structures for the anion C3NO are :C=C=C=N--O and N
      triple bond C-C triple bond C--O-. The unique CID behavior of C6F5CH2--NO2 can be
      utilized to unequivocally identify and accurately quantify nitrite in biological
      fluids by GC-tandem MS.

PMID- 15844541
TI  - Chiral separations by capillary electromigration techniques in nonaqueous media.
      I. Enantioselective nonaqueous capillary electrophoresis.
AB  - Enantiomer separations by CE employing nonaqueous conditions are reviewed. The
      general focus of this article is directed towards solvent effects on chiral
      recognition and the separation mechanism. After a general discussion of solvent
      effects on the individual processes involved in CE enantiomer separation,
      specifics for various selector classes are discussed together with a few
      applications of enantioselective nonaqueous CE.

PMID- 15844542
TI  - Chiral separations by capillary electromigration techniques in nonaqueous media.
      II. Enantioselective nonaqueous capillary electrochromatography.
AB  - A review on the advantages, peculiarities, and the potential of enantioselective
      capillary electrochromatography (CEC) in nonaqueous media is presented. Some
      fundamentals on CEC with particular focus on enantioselective CEC are discussed.
      The strategies, concepts, preferentially utilized chiral selectors and column
      technologies that have been utilized to succeed in highly efficient enantiomer
      separations by nonaqueous CEC are described thoroughly.

PMID- 15844543
TI  - Nonaqueous and aqueous capillary electrophoresis of synthetic polymers.
AB  - In this work, the use of capillary electrophoresis (CE) to analyze synthetic
      polymers is reviewed including works published till February 2004. The revised
      works have been classified depending on the CE mode (e.g., free solution
      capillary electrophoresis, capillary gel electrophoresis, etc.) and type of
      buffer (i.e., nonaqueous, aqueous and hydro-organic background electrolytes)
      employed to separate synthetic macromolecules. Advantages and drawbacks of these
      different separation procedures for polymer analysis are discussed. Also,
      physicochemical studies of complex polymer systems by CE are reviewed, including
      drug release studies, synthetic polyampholytes, dendrimers, fullerenes, carbon
      nanotubes and associative copolymers.

PMID- 15844544
TI  - Determination of electroosmotic flow in nonaqueous capillary electrophoresis.
AB  - Mobility of the electroosmotic flow (mu(EOF)) in fused-silica capillaries
      strongly depends on the nature of the background electrolyte. In this study, 27
      solvent systems were investigated, namely water, methanol, ethanol, 2-propanol, 1
      butanol, acetonitrile (MeCN), formamide, N-methylformamide (NMF), N,N
      dimethylformamide and dimethyl sulfoxyde, as well as 8 hydroorganic and 9 organic
      mixtures. For each system, six mu(EOF) were determined at a different ionic
      strength in basic conditions, and an absolute electroosmotic flow mobility
      (mu(EOF,0)) was extrapolated according to the Debye-Huckel Onsager model. The
      obtained mu(EOF,0) values were correlated with the solvent's relative
      permittivity (epsilon) and viscosity (eta). A good correlation (r2=0.867) between
      mu(EOF,0) and the solvent's epsilon/eta ratio was demonstrated, except for two
      solvents (MeCN and NMF). Furthermore, the donor number (DN) of a solvent took
      into account the possible zeta potential modification in the electric double
      layer near the capillary wall. Consequently, the relationship between mu(EOF,0)
      and epsilon/(eta x DN) was superior, with a r2 of 0.943 for 10 pure solvents.

PMID- 15844545
TI  - Specific background electrolytes for nonaqueous capillary electrophoresis.
AB  - The use of organic solvents or mixture of solvents in capillary electrophoresis
      is gaining wider attention. The electroosmotic flow mobility of eight organic
      solvents (acetonitrile, acetone, dimethylformamide, dimetylsulphoxide, propylene
      carbonate, methanol, ethanol, n-propanol) and of mixtures of several solvents
      (methanol-acetonitrile, methanol-propylene carbonate, acetonitrile-propylene
      carbonate) has been studied. The influence of 1,3-alkylimidazolium salts in
      different solvents on the separation of different analytes has been investigated.
      Some of these salts have shown usefulness for matrix-assisted laser desorption
      ionization matrices and off-line analysis of electrophoresis fractions. It also
      appears that nonaqueous capillary electrophoresis with 1,3-alkylimidazolium salts
      as background electrolytes is suitable for separation small inorganic ions.

PMID- 15844546
TI  - Capillary zone electrophoresis of cationic and anionic drugs in methanol.
AB  - The actual mobilities and dissociation constants of acidic and basic
      pharmaceuticals were determined in methanol. Actual mobilities were derived from
      the dependence of the effective mobilities of the analytes on the pH of the
      methanolic background electrolyte solution (pH(MeOH)). The pKa values of the
      pharmaceuticals in methanol (pK(a,MeOH)) were calculated by non-linear curve
      fitting to the measured mobility values. It was found that the shift in pKa value
      (when compounds were transferred from water to methanol) increased with the
      acidity of the analyte. The average pKa shift for compounds exhibiting acidic
      properties in water was ca. 5.5 units, and the shift for basic compounds about 2
      units. As was shown for a mixture of beta-blockers, the calculated actual
      mobilities and pKa values can be utilised in the optimisation of pH conditions
      for separation. The practical value of the method was illustrated by the analysis
      of urine samples.

PMID- 15844547
TI  - Determination of the dissociation constants (pKa) of secondary and tertiary
      amines in organic media by capillary electrophoresis and their role in the
      electrophoretic mobility order inversion.
AB  - Non-aqueous capillary electrophoresis (NACE) may provide a selectivity
      enhancement in separations since the analyte dissociation constants (pKa) in
      organic media are different from those in aqueous solutions. In this work, we
      have studied the inversion in mobility order observed in the separation of
      tertiary (imipramine (IMI) and amitryptiline (AMI)) and secondary amines
      (desipramine (DES) and nortryptiline (NOR)) in water, methanol, and acetonitrile.
      We have determined the pKa values in those solvents and the variation of
      dissociation constants with the temperature. From these data, and applying the
      Van't Hoff equation, we have calculated the thermodynamic parameters deltaH and
      deltaS. The pKa values found in methanol for DES, NOR, IMI, and AMI were 10.80,
      10.79, 10.38, and 10.33, respectively. On the other hand, in acetonitrile an
      opposite relation was found since the values were 20.60, 20.67, 20.74, and 20.81
      for DES, NOR, IMI, and AMI. This is the reason why a migration order inversion is
      observed in NACE for these solvents. The thermodynamic parameters were evaluated
      and presented a tendency that can be correlated with that observed for pKa
      values.

PMID- 15844548
TI  - Effect of initial voltage ramp on separation efficiency in non-aqueous capillary
      electrophoresis with ethanol as background electrolyte solvent.
AB  - Band broadening at high electric field strengths in capillary electrophoresis
      (CE), especially in wide capillaries, is often attributed to radial temperature
      gradients in the interior of the capillary caused by Joule heating. In some
      cases, however, a major cause of the lower separation efficiency could be the
      abrupt application of high electric field strength. We show that, with ethanol as
      background electrolyte solvent, initial abrupt voltage application introduces
      band broadening, which is especially pronounced in wider capillaries at high
      electric field and ionic strengths. With an appropriate initial voltage ramp this
      effect can be avoided. The effect of different voltage ramp up times on the
      separation efficiency of some anionic analytes was investigated with 50, 75 and
      100 microm I.D. capillaries at field strengths of 1000-2000 V cm(-1). The results
      suggest that the band broadening associated with abrupt voltage application is of
      thermal origin and probably related to thermal volume expansion of the sample and
      background electrolyte solutions. The plate numbers calculated with a plate
      height model were in good agreement with the experimental values when a
      sufficiently long voltage ramp was employed. The dispersion due to axial
      temperature gradients was found to be very small under the experimental
      conditions used.

PMID- 15844549
TI  - Sample-stacking techniques in non-aqueous capillary electrophoresis.
AB  - In sample-stacking techniques, the detection limit cannot be improved by simply
      increasing the length of the sample solution, because the individual
      electrophoretic parameters must be optimized. In an attempt to increase the
      amount of sample injected, as well as to focus them onto a small zone, two novel
      methods are proposed. One of these employs an "ultra-high conductivity zone",
      which was inserted between the sample zone and background solution to build an
      unequal conductivity gradient. The other employs a "low temperature bath". A
      portion of the capillary (near the junction between the sample solution and the
      background solution) was immersed in a low temperature bath, which served as a
      "pseudo-high-conductivity zone" due to the fact that conductivity would increases
      when the temperature is decreased. As a result, a large volume of sample
      injection can be achieved. Using 3,4-methylenedioxymethamphetamine as a model
      compound, the detection limit was determined to be 1.6 x 10(-6) M (S/N = 3) by
      means of normal non-aqueous capillary electrophoresis (NACE). This could be
      improved to 3.0 x 10(-8) M, 4.8 x 10(-9) M and 5.0 x 10(-9) M, respectively, when
      the normal stacking, ultra-high conductivity zone NACE-stacking and the low
      temperature zone NACE-stacking methods were applied.

PMID- 15844550
TI  - Enhanced detection of seven glucoconjugated and hydroxylated porphyrins and
      chlorins by nonaqueous capillary electrophoresis combined with stacking.
AB  - The nonaqueous capillary electrophoresis mode which includes a preconcentration
      step based on a transient pseudo-isotachophoresis to the simultaneous separation
      of seven glucoconjugated and hydroxylated porphyrins and chlorins, exhibiting
      very close structures, is reported. A high methanol content, of the buffer
      solution, was necessary in order to prevent self-assembly of the compounds and to
      enhance their solubility during separation. With the addition of 66% (v/v)
      methanol and 1% (w/v) NaCl in the aqueous sample solution, large volumes could be
      injected (44% capillary volume) without a loss in resolution. Sensitivity of
      detection was therefore improved by a 100-fold factor with regard to the method
      employing normal injection (2% capillary volume). Optimum electrophoretic
      conditions, in terms of sensitivity and performance, were obtained by using 20 mM
      phosphoric acid buffer, pH 2.2 and 50% methanol. The method was validated and
      applied to qualitative analysis of glucoconjugates in serum samples.

PMID- 15844551
TI  - Influence of solvent properties on separation and detection performance in non
      aqueous capillary electrophoresis-mass spectrometry of basic analytes.
AB  - The versatility of non-aqueous capillary electrophoresis (NACE) results mainly
      from the variety of physico-chemical properties of the different solvents. They
      provide solubility for a wide range of analytes, enable to control
      electrophoretic selectivity, but affect in some cases UV absorbance detection.
      The coupling of NACE to electrospray mass spectrometry (ESI-MS) allows to cope
      with the high UV cut-off of some CE relevant solvents (e.g., formamides). In this
      paper the pure organic solvents methanol, acetonitrile, dimethylsulfoxide,
      formamide, N-methylformamide and N,N-dimethylformamide are evaluated against
      water for the preparation of ammonium acetate electrolytes to separate the basic
      model substances 2-aminobenzimidazole, procaine, propranolol and quinine with
      NACE-MS. MS coupling is assisted with the sheath liquid water-isopropanol (1:4,
      v/v) with 0.1% formic acid. The goal of the paper is to assess the influence of
      the solvent on selectivity, separation speed, and peak efficiency for a given set
      of model compounds on a simple empirical basis. It should give the user an idea
      how the separation quality is changed when nothing but the running solvent is
      altered. The obtained efficiency results were discussed with respect to physico
      chemical models described in literature (assuming longitudinal diffusion as the
      only source of band broadening), but no satisfying correlations with solvent
      properties could be traced. The feasibility of all six organic solvents for MS
      coupling was demonstrated and the influence of the separation solvent on the MS
      detection performance was compared. In the seven different solvents, the shortest
      run time was obtained with acetonitrile, the best peak resolution with the
      amphiprotic solvents (especially methanol) best peak efficiency with methanol and
      formamide, and the most sensitive ESI-MS detection with acetonitrile and
      methanol, but with only slight advantage to water.

PMID- 15844552
TI  - Influence of the nature of the electrolyte on the chiral separation of basic
      compounds in nonaqueous capillary electrophoresis using heptakis(2,3-di-O-methyl
      6-O-sulfo)-beta-cyclodextrin.
AB  - The influence on the enantiomeric resolution of the nature of the cationic BGE
      component (sodium, ammonium or potassium) and that of the anionic component
      (chloride, formate, methanesulfonate or camphorsulfonate) as well as the
      concentration of heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin (HDMS-beta
      CD), the selected chiral selector, was studied in nonaqueous capillary
      electrophoresis (NACE). For this purpose, two D-optimal designs with 33 and 26
      experimental points were applied. Three beta-blockers (atenolol, celiprolol and
      propranolol) and three local anesthetics (bupivacaine, mepivacaine and
      prilocaine) were selected as basic model compounds. Both cationic and anionic BGE
      components were found to have a deep impact on the enantiomeric resolution of the
      investigated analytes but it is the cationic component that has shown the
      strongest influence. Indeed, in some cases, the change of the latter led to a
      complete loss of enantioresolution. Based on the observed results, two NACE
      systems were recommended, namely ammonium formate and potassium camphorsulfonate
      in a methanolic solution containing HDMS-beta-CD and acidified with formic acid,
      in order to separate efficiently the enantiomers of basic drugs.

PMID- 15844553
TI  - Non-aqueous capillary electrophoretic enantiomer separations using the
      tetrabutylammonium salt of heptakis(2,3-O-diacetyl-6-O-sulfo)-cyclomaltoheptaose,
      a single-isomer sulfated beta-cyclodextrin highly-soluble in organic solvents.
AB  - The tetrabutylammonium salt of heptakis(2,3-di-O-acetyl-6-O-sulfo)
      cyclomaltoheptaose, a single-isomer sulfated beta-cyclodextrin that is adequately
      soluble in a number of protic and aprotic polar solvents was synthesized on the
      large scale and used for the capillary electrophoretic separation of the
      enantiomers of weak bases in acidic acetonitrile background electrolytes. The
      effective mobilities and separation selectivities observed for these analytes
      followed trends similar to those found with other single-isomer sulfated
      cyclodextrins in acidic methanol background electrolytes. Enantiomer separations
      obtained with the tetrabutylammonium and sodium salts of heptakis(2,3-di-O-acetyl
      6-O-sulfo)-cyclomaltoheptaose were different indicating, for the first time, that
      selection of the counter ion of the single-isomer sulfated cyclodextrin is also
      of importance for the separation of enantiomers.

PMID- 15844554
TI  - Analysis of neutral surfactants by non-aqueous capillary electrophoresis using an
      electroosmotic flow reversal.
AB  - The separation of KM 20, that is in fact a mixture of non-ionic surfactants, was
      carried out by non-aqueous capillary electrophoresis. This complex mixture
      resulting from the condensation of ethylene oxide with fatty alcohols does not
      have chromophoric moieties. So, we analysed it after derivatization by means of
      3,5-dinitrobenzoyl chloride. The proposed approach is based both on the formation
      of complexes with alkaline or ammonium cations in methanol and on the utilisation
      of a positively charged capillary. From a comparative study on the capillary
      treatment procedure, we used hexadimethrine bromide as electroosmotic flow
      reverser in order to obtain both repeatable analyses and good resolutions of the
      largest KM 20 oligomers. Then, among the five cations used to form complexes with
      KM 20, we pointed out that ammonium cation led to the best resolutions. Moreover,
      we evidenced that the counter-ion of this cation had a great influence on
      resolution because it modified the magnitude of electroosmotic flow. Ion pair
      formation that is more or less strong between ammonium and its counter-ion was
      involved in this variation of electroosmotic flow. So, we calculated the
      association constants for various ammonium salts in methanol. Then, using
      ammonium chloride as background electrolyte, we optimised the concentration of
      this salt, in methanol, in order to reach the optimal separation of KM 20
      oligomers. Thus, a baseline separation was obtained by using 6 x 10(-2) mol/L
      NH4Cl as running electrolyte. In these conditions, we separated, in about 30 min,
      more than 30 oligomers of KM 20. The distribution of these oligomers that was
      determined from the optimal separation, appeared consistent with that obtained
      from HPLC analyses. Indeed, we determined that the mean ethoxylation number was
      equal to 18 while its real value is equal to 20.

PMID- 15844555
TI  - Separation of transition metals in nonaqueous media with capillary
      electrophoresis.
AB  - The separation of transition metal Ni2+, Cu2+, Co2+, Zn2+, Cd2+ and Fe3+ in
      methanol was investigated by using different types of organic acids as complexing
      agents. In pure methanol, the weaker and simpler acetic, propionic, butyric and
      valeric acids could enhance metal ions selectivity by increasing acid
      concentration and metal ions could be separated with high efficiency. However,
      hydroxycarboxylic acids obviously made separation efficiency worse. The effect of
      mixed organic acids, mixture solvent (methanol-acetonitrile, methanol-water) on
      metal ions separation was discussed further. The advantages of using nonaqueous
      solvent over aqueous for metal ions separation were shown finally.

PMID- 15844556
TI  - Nonaqueous capillary electrophoresis method for the analysis of gleevec and its
      main metabolite in human urine.
AB  - The viability of nonaqueous capillary electrophoresis (NACE) was investigated for
      determination of gleevec and its main metabolite in human urine using a fused
      silica capillary. Baseline separation of the studied solutes was obtained using a
      nonaqueous solution composed of 12 mM ammonium acetate and 87.6 mM acetic acid in
      methanol-acetonitrile (ACN) (80:20, v:v) providing analysis time shorter than 3
      min. Different aspects including stability of the solutions, linearity, accuracy
      and precision were studied in order to validate the method in the urine matrix.
      Detection limits of 24 microg L(-1) for gleevec and its metabolite were obtained.
      A robustness test of the method was carried out using the Plackett-Burman
      fractional factorial model with a matrix of 15 experiments. The developed method
      is simple, rapid and sensitive and has been used to determine gleveec and its
      metabolite at clinically relevant levels in human urine. Before NACE
      determination, a solid-phase extraction (SPE) procedure with a C18 cartridge was
      necessary. Real determination of these analytes in two patient urines were done.

PMID- 15844557
TI  - Contactless conductivity detection of synthetic polymers in non-aqueous size
      exclusion electrokinetic chromatography.
AB  - A capacitively coupled contactless conductivity detection (CCD) system has been
      applied for the detection of neutral synthetic polymers in capillary size
      exclusion electrokinetic chromatography (SEEC). Polystyrene standards, that were
      used as a model compounds, were separated on a capillary column packed with
      porous 10 microm silica particles with an electrokinetically driven mobile phase,
      and detected by CCD and UV detection simultaneously. Mass-calibration curves for
      polystyrene were constructed. Satisfactory results were obtained for the
      linearity, the run-to-run repeatability (<0.2% for the relative retention and <4%
      for the peak area) and the robustness of the detector. One of the major issues in
      this preliminary study was to investigate the origin of the peaks observed for
      the polystyrene standards. The effect of the molar mass of the polystyrenes on
      the sensitivity was small. Therefore, the signals obtained could not be explained
      as the result of an increased viscosity and a decreased solution conductivity of
      the solute zone. An alternative hypothesis is suggested, and recommendations for
      further research are given.

PMID- 15844558
TI  - Comparative study of aqueous and non-aqueous capillary electrophoresis in the
      separation of halogenated phenolic and bisphenolic compounds in water samples.
AB  - Capillary zone electrophoresis methods, based on either aqueous and non-aqueous
      solutions as running buffers and UV spectrophotometric detection, have been
      developed and optimized for the separation of several halogenated phenolic and
      bisphenolic compounds, suspected or proved to exhibit hormonal disrupting
      effects. Both aqueous capillary electrophoresis (CE) and non-aqueous capillary
      electrophoresis (NACE) methods were suitable for the analysis of compounds under
      study. The separation of the analytes from other 25 potentially interfering
      phenolic derivatives was achieved with NACE method. Large-volume sample stacking
      using the electroosmotic flow pump (LVSEP) was assayed as on-column
      preconcentration technique for sensitivity enhancement. LVSEP-CE and LVSEP-NACE
      improved peak heights by 5-26 and 16-330 folds, respectively. To evaluate their
      applicability, the capillary electrophoresis methods developed were applied to
      the analysis of water samples, using solid-phase extraction as sample pre
      treatment process.

PMID- 15844559
TI  - [First trimester diagnosis of chromosomal defects].
AB  - Fetal nuchal translucency thickness at the 11(+0) - 13(+6) weeks scan has been
      combined with maternal age to provide an effective method of screening for
      trisomy 21; for an invasive testing rate of 5%, about 75% of trisomic pregnancies
      can be identified. When maternal serum free B-human chorionic gonadotropin and
      pregnancy-associated plasma protein-A at 11(+0) - 13(+6) weeks are also taken
      into account, the detection rate of chromosomal defects is about 85-90%. In 60
      70% of fetuses with trisomy 21 the nasal bone is not visible at the 11(+0) -
      13(+6) weeks scan and examination of the nasal bone can increase the detection
      rate of screening by the first trimester scan and serum biochemistry to more than
      95%.

PMID- 15844560
TI  - [The relationship of the expression of proliferetron--related antigens Ki67 and
      PCNA in the cells of ductal breast cancer with the differentiation grade].
AB  - OBJECTIVES: Ki67 and PCNA proteins are characteristic for cells in mitotic cycle
      and represent unfavourable prognostic indices. Intensity of the proteins
      expression directly correlates with grade of tumour differentiation. They belong
      to the second category of prognostic factors in breast cancer according to the
      College of American Pathologists. DESIGN: Present study aimed at examining the
      relationship between intensity of expression of proliferation-related antigens-
      Ki67 and PCNA in cells of ductal breast cancer of G1, G2 or G3 differentiation
      grade. MATERIALS AND METHODS: In paraffin sections of 60 ductal breast cancers,
      immunocytochemical reactions were performed to detect expression of Ki67 and
      PCNA. Following semiquantitative appraisal of studied preparations, appropriate
      statistical tests were used to document statistical relationships. RESULTS:
      Intensity of Ki67 expression was most pronounced in G3 group and least pronounced
      in G1 group (ANOVA rang Kruskal-Wallis, p=0.00001). In the case of PCNA we did
      not show any differences. Only in the G1 we showed a positive correlation between
      expression intensity of studied antigens (Spearmans rang correlation, r=0.67,
      p=0.024). CONCLUSIONS: The study showed that Ki67 and not PCNA correlates with
      morphologic features of proliferation.

PMID- 15844561
TI  - [The role of preoperative hooked-wire localization of occult lesions for early
      detection of breast cancer].
AB  - OBJECTIVES: Nonpalpable small lesions, usually few millimeters in diameter,
      consist an important problem in the early diagnostics of breast cancer. DESIGN:
      An aim of this paper was an evaluation of usefulness of preoperative hooked-wire
      localization of such lesions for the detection of breast cancer. MATERIALS AND
      METHODS: Material consisted of 131 patients aged 37-77 in whom 132 procedures of
      preoperative hooked-wire localization were performed. The correlation between the
      mammographic findings and the cytologic or histologic results were then
      evaluated, with the histologic results being treated as standard. RESULTS:
      Histologic examination of the localized lesions revealed benign changes in 71.2%,
      atypical ductal hyperplasia in 4.6% and cancer in 24.2%. Positive predictive
      value for mammography was 24%. Significant correlation was seen between the
      suspicion of cancer in mammography and the histologic results. CONCLUSIONS:
      Preoperative localization should be used as a method of choice in radial lesions,
      suspected clustered microcalcifications and after the positive result from SFAB.

PMID- 15844562
TI  - [Significance of laparoscopic assistance in vaginal hysterectomy].
AB  - OBJECTIVE: The objective of this publication was the analysis of laparoscopically
      assisted vaginal hysterectomies (LAVH) performed in Department of Surgical and
      Endoscopic Gynecology of Polish Mother Health Centre Research Institute.
      MATERIALS AND METHODS: There was the analysis of 57 LAVHs performed from June
      2002 to December 2003. Following parameters were evaluated: indications to LAVH,
      operating time, weight of the removed uterus, complications, blood loss, duration
      of postoperative hospitalisation, the day of introducing general diet, anesthetic
      and antibiotic demand in postoperative period. RESULTS: There were indications to
      LAVH: fibroid uterus, endometrial hyperplasia, endometrial cancer, adnexal mass,
      cervix dysplasia. Previous laparotomy and caesarean section, endometriosis,
      narrow vagina of non-parous women were additional indications to use of
      laparoscopy during the operation. Complications were found in two (3,5%) cases:
      bleeding to abdominal cavity from infundibulo-pelvic ligament demanding
      reoperation and superficial epigastric artery injury no demanding reoperation.
      There were no infection, conversion to laparotomy, abdominal cavity organs injury
      and other complications. It was observed short time of introducing general diet,
      low anesthetic consumption and short post-operation stay in hospital (mean 3,6
      days). CONCLUSIONS: Laparoscopically assisted vaginal hysterectomy is an
      operation with a small risk of intra- and postoperative complications, quick
      return to general diet and full life activity, short post-operation stay in
      hospital, low anesthetic consumption and good cosmetic effect. Use of
      laparoscopic stage in vaginal hysterectomy make possible evasion of laparotomy in
      the situation of impossible performance of ordinary vaginal hysterectomy.

PMID- 15844563
TI  - [Left lateral predisposition of endometrioma].
AB  - OBJECTIVE: To investigate whether asymmetry exists in the left- and right-handed
      distribution of ovarian cystic lesions in women with endometriosis. MATERIALS AND
      METHODS: We evaluate operative reports of women who underwent first line surgical
      treatment of endometrioma (n=154) from January 2000 to December 2002. Data of all
      operative findings consisted of a written report, and a diagram, the revised
      American Fertility Society classification of endometriosis. RESULTS: Endometrioma
      was found in the left ovary (n=81), in the right ovary (n=39), and bilaterally
      (n=34). Left ovarian endometrioma was found more frequently (67,5%) than the
      right endometrioma (P<.001, odds ratio 2.3, 95% confidence interval 1.5, 3.7).
      This trend was not related to the size of the endometrioma. CONCLUSION: Our
      results confirm a left lateral predisposition of ovarian endometrioma. It is
      probably caused by the decreased fluid movement in the left side of the pelvis
      because of the presence of sigmoid colon. These findings may support the theory
      that the origin of endometriosis is from the regurgitated endometrial cells.

PMID- 15844564
TI  - [A morphometric evaluation of the maturity of the blood-blood barrier in the
      human placenta].
AB  - Computer aided analysis of microscopic picture was used to morphometric
      examination of 506 placentas from normal pregnancies at 30 to 42 gestational
      weeks. Following parameters of the terminal villi: diameter and its number within
      1mm2, the length, the thickness, the number of epithelial plates in 1mm2, the
      number of epithelial plates for the villus within 1mm2, seem to be the
      morphological signs of maturity of the blood-blood barrier in the placenta. In
      previous studies it has been found that in pregnancies with hypertension or
      abnormalities in KTG, parameters of blood-blood barrier respond earlier stages of
      the pregnancy. A maturity of the placental barrier correlates with some somatic
      features of a foetus and a newborn. Our results show that between 30 and 42
      gestational week some parameters of the placental barrier have a linear increase
      and others grow rapidly between 35 and 38 gestational age and after 38
      gestational age do not change. According to obtained results, we drew a
      conclusion, that between 30 and 42 gestational age there are rapid morphological
      transformations of the structures formed placental barrier and that morphometry
      of the human placenta may be used as a more objective and accurate method to
      estimate gestational age.

PMID- 15844565
TI  - [Comparative analysis of labor in twin pregnancies in years 1987-91 and 1997
      2001].
AB  - OBJECTIVE: The aim of the study was to evaluate the course of twin pregnancy
      deliveries with particular regard to parity, the way of pregnancy termination,
      indications for cesarean section and sterility treatment. MATERIALS AND METHODS:
      The studied material consisted of two groups of patients who gave birth to twins
      in our clinic: the first one of 62 women in years 1997-2001 and the second group
      of 92 women in years 1987-1991. The average age of patients was 29.4 vs 28.7
      respectively. RESULTS: There were 48.3% of primiparas in the first group,
      comparing to 44.5% in the second. The average time of pregnancy termination was
      35 vs 35.97 Hbd respectively. Premature labours contributed to 80.6% vs 52% of
      all cases, which was statistically significant (p<0.001). Obstetrical procedures
      were applied in 6.5% vs 25% of cases respectively (p = 0.003). The indications
      for cesarean section have changed in regard to the position of the second fetus
      (when first in cephalic longitudinal lie, second in other than cephalic) and
      therefore contributed to 78.5% of cases in first and only 12.5% in second group.
      Thus the application of obstetrical procedures on the second fetus decreased to
      18.2% vs 63% (p=0.002). In both groups cesarean sections were most often
      performed when the position of the first fetus was other than cephalic. In both
      groups the mediana of Apgar score of the second twin was lower than of the first.
      But the number of stillborns and general neonatal deaths significantly decreased
      over the years (0.8% and 2.4% vs 4.9% and 5.36%). Comparing both studied groups,
      the rate of the twin pregnancy after sterility treatment is rising: 16% vs 7.6%.
      CONCLUSIONS: The significance of the second twin position as an indication for
      cesarean delivery has risen over the years, thereby displacing the use of
      obstetrical procedures in those cases. In spite of earlier pregnancy termination
      and higher premature labour rate, there is a significant drop in the number of
      stillborns and neonatal deaths. In the age of infertility treatment, the number
      of twin pregnancy is rising.

PMID- 15844566
TI  - [The mode of anaesthesia for caesarean section in the opinion of pregnant and
      delivering women].
AB  - OBJECTIVES: Conduction anaesthesia is regarded as a very safe method for the
      mother and for a newborn. This kind of anaesthesia reduces the risk of gastric
      contents aspiration and does not cause the respiratory depression. However in
      every case it is essential to take into consideration the woman's opinion, for
      whom delivering of the child is the particularly important event. DESIGN: The aim
      of the study was the evaluation the presence and the intensification grade of
      side effects of the anaesthesia to the caesarean section and establishing, which
      kind of anaesthesia to this operation: general or conduction is assessed as the
      best method for the delivering women. RESULTS: In study group among 76 women
      after cesarean section were 49 (64.5%) after epidural anaesthesia, 22 women
      (28.9%)--after spinal anaesthesia, and 5 patients (6.6%) were operated in general
      anaesthesia. The most common side effects after anaesthesia for cesarean section
      were: weakness and backache. After POP the headache was much more often symptom.
      CONCLUSIONS: Most of pregnant women preferred epidural anaesthesia during
      delivering of the child by caesarean section.

PMID- 15844567
TI  - [Intrauterine death of one fetus during the first trimester of monochorionic
      diamniotic twin gestation].
AB  - OBJECTIVES: The goal of our study was the clinical and pathological
      characteristics of the monochorionic diamniotic twin gestations complicated by
      the intrauterine death of one fetus during the first trimester. MATERIAL AND
      METHODS: This study is a prospective review of 9 monochorionic diamniotic twin
      gestations involving the intrauterine death of one fetus during the first
      trimester. RESULTS: During the study period 178 twin gestations were identified
      sonographically during the first trimester. Forty three of them (24,2%) were
      complicated by the intrauterine death of one fetus before the end of 12th
      gestation week. Nine cases were monochorionic diamniotic. Gestational age of one
      fetus demise ranged from 5 to 11 (mean 7,4) weeks. Prognoses for surviving fetus
      were adverse. In 8 cases there was a death of a second fetus after the period of
      1 to 3 weeks, with abortion of both fetuses. Only in one case, the gestation has
      finished in 40th week by delivery of liveborn infant. Maternal coagulation
      changes did not occur in those cases. One liveborn infant was without evidence of
      hematological and neurological abnormalities. The postdelivery examination
      allowed to establish a presence of monochorionic diamniotic placentation in all
      cases. In two of them, the probable causes of death were established
      (developmental defect, presence of anastomoses between blood vessels).
      CONCLUSION: These results suggest that the risk of mortality for the living twin
      is very high, after the death of its sibling, in case of monochorionic
      placentation. Morphological examination of placenta and fetal membranes lets to
      establish a type of placenta, and in some cases a probable cause of intrauterine
      death of one twin during the first trimester of monochorionic diamniotic twin
      gestation.

PMID- 15844568
TI  - [Abdominal aortic-iliac thrombosis as a complication of newborn's bacterial
      sepsis].
AB  - A case of Group B Streptococcus sepsis is reported in a male newborn with a renal
      vascular hypertension. An abdominal Doppler examination revealed aortic
      thrombosis extending from renal to the common iliac arteries. Prolonged broad
      spectrum antibiotic therapy and fibrinolytic treatment combined with surgical
      thrombectomy were used, at last obtaining improvement of general patient
      condition. The infant's hypertension resolved and reperfusion of the right kidney
      and urine output resumed. Ultrasound examination at 4th month showed presence of
      collateral circulation to arteries providing right lower limb. Patient's long
      term out come is still under control of Outpatient Department of Vascular
      Surgery.

PMID- 15844569
TI  - Pregnancy-associated osteoporosis manifesting for the first time during second
      pregnancy.
AB  - We present here a case of 26-year-old woman with pregnancy-associated severe
      osteoporosis which occurred for the first time at the end of the second
      pregnancy. We discuss changes in bone mass and metabolism taking place during
      normal pregnancy and other possible factors of osteoporosis during that period.

PMID- 15844570
TI  - [Chemokines in the diagnosis of neonatal infections].
AB  - Bacterial infection is a major cause of neonatal morbidity and mortality. The
      increased susceptibility of the neonate especially premature one, for bacterial
      infection is the result of several factors including a delayed maturation of
      immune response of neonatal B and T cells and deficiencies of the myelopoetic
      system. Chemokines constitute a large family of chemotactic cytokines with
      proinflammatory action, which are produced by large variety of cells. Although
      most inflammatory chemoatractants are only induced and released in the
      circulation during acute infection Large epidemiology studies are needed to
      clarify relationships among inflammation markers and their expression in the
      fetal and neonatal circulation over time. Such studies would also add to our
      understanding of the possible role of chemokines in the pathophysiology of the
      major complications of the neonate, especially premature one.

PMID- 15844571
TI  - [Amniotic fluid analysis. Part I: Rapid markers in the prediction of intra
      amniotic infection].
AB  - Intraamniotic infection has been recognized as a major etiologic factor for
      preterm delivery. Several groups have proposed that amniocentesis be used to
      identify the patient at risk for infectious morbidity. The number of techniques
      have been studied for rapid identification of bacterial colonization of amniotic
      cavity. Diagnostic index value of Gram stain, white blood cell count, glucose
      level and LDH (lactate dehydrogenase) activity for prediction of positive
      amniotic fluid culture, preterm delivery, clinical infection and neonatal sepsis
      were shown in the study. Investigators continue attempts to establish a rapid,
      more useful tests to predict preterm delivery.

PMID- 15844572
TI  - [Study of immunoregulation of dendritic cells in allergic rhinitis].
AB  - OBJECTIVE: To investigate the immunoregulation of dendritic cells in allergic
      rhinitis. METHOD: Adopting the cell culture and the enzyme linked immunosorbant
      assay to examine the patients' Th1/Th2 in the blood. Observing that how is the
      DC's function in immunoregulation of allergic rhinitis. RESULT: The concentration
      of the IFN-gamma advanced obviously in post-stimulatory supernatant liquid after
      using the mature DC. CONCLUSION: The mature dendritic cells can polarize naive T
      cells into Th1 effector cells, and are recognized as having a central role in the
      establishment of T-cell memory and peripheral immune tolerance. DC could be
      exploited as targets for therapy in asthma and allergic rhinitis.

PMID- 15844573
TI  - [Experiment of genes expression of chemokines and their receptors in allergic
      rhinitis with gene chip].
AB  - OBJECTIVE: To analyze the role of chemokines and their receptors in the mechanism
      of allergic rhinitis (AR) by observing the expression of genes of chemokines and
      their receptors in nasal mucosa of AR through gene chip. METHOD: The total RNAs
      were isolated from nasal mucosa of AR and purified to mRNAs, then reversely
      transcribed to cDNAs and incorporated with fluorescent-labled CY5-dUPT for probes
      preparion. CY3-dUTP probes prepared with normal nasal mucosa of normal for
      control. The chip contains cDNAs of chemokines and their receptors were used to
      hybridized with probes then screened with computer to study the expression of
      genes based on different density of fluorescent. RESULT: The chemokines of CCL11
      (eotaxin-1), CCL24 (eotaxin-2), CCL7 (MCP-3), CCL13 (MCP-4), RANTES (CCL5) and
      receptors of CCR2, CCR3, CCR4, CCR5 were differential expressed on four samples,
      and most of the chemokines and their receptors has tendency regulation on T help
      2 (Th2) lymphocytes and involved in the prodeeds such as inducement of allergic
      reaction,accumulation of inflammacytes and degranulation of sensitized cells.
      CONCLUSION: A disorder exists in T helper immune system with AR. The chemokines
      and their receptors that polarized with Th2 lymphocytes perhaps play important
      roles in AR pathogenesis, and it represents a new approach to AR immunotherapy.

PMID- 15844574
TI  - [Surgery of osteomas of the sinuses].
AB  - OBJECTIVE: To explore the different surgical choices for treating osteomas of the
      sinuses. To summarize the management and characteristics of each surgical
      operation. METHOD: A retrospective evaluation of thirty-one patients with
      osteomas of the sinuses from June 1993 to December 2001 was presented. Fourteen
      patients were operated through a lateral rhinotomy with radical operation in 13
      cases. Eight patients were operated by nasal endoscopic management, osteomas were
      completely removed. Eight osteomas were removed with a coronal incision. One case
      underwent Caldwell-Luc surgery. The clinical symptoms, location of osteomas, and
      surgical procedures were analyzed. RESULT: The complications of brain spinal
      fistula occurred in 2 cases, but they were treated in the same time of
      operations. One patient had a single blindness after the operation. Twenty-eight
      cases were followed-up for 1 to 9 years with an average of three point seven
      years. Twenty-six patients had no recurrence, two cases lived with the remains of
      osteomas. CONCLUSION: The choice of surgical operations on osteomas of the
      sinuses was mainly decided by the location and size of osteomas, and the anatomic
      characteristics of sinuses, in the meanwhile, the organ function, the
      cosmetology, and the doctors experience were taken into account.

PMID- 15844575
TI  - [The endoscopic extended transsphenoidal surgery for gigantic pituitary adenoma].
AB  - OBJECTIVE: The purpose of the study is to evaluate the ability of endoscopic
      extended transsphenoidalapproach for treatment of gigantic pituitary adenoma.
      METHOD: The clinical data of 13 cases with gigantic pituitary adenoma treated by
      endoscopic extended transsphenoidalapproach was studied retrospectively. RESULT:
      The tumor of all patients was total resection in endoscopes. Postoperative 10
      Patients received radiotherapy. In postoperative MRI examination, there was
      remnant of tumor in 6 patients. There were no regrowth or recurrence during 12
      months postoperative. Six patients occurred transient diabetes insipidus, 2
      patients with transient cerebrospinal rhinorrhoea cured by conservative therapy.
      One patient occurred acute hypopituitarism postoperatively. There were no death
      or intracranial infection and nasal complication such as nasal adherence in all
      patients. CONCLUSION: The extended transsphenoidalapproach can be used for
      treatment of gigantic pituitary tumor. The surgeon should be familiarity with the
      sellar and parasellar anatomy and skilled with transsphenoidal surgery.

PMID- 15844576
TI  - [The clinical study of multi-slice helical CT three-dimensional reconstruction in
      the sphenopalatine foramen].
AB  - OBJECTIVE: Used multi-slice helical CT to observe the reconstruction of the
      surface structure of nasal lateral wall "sphenopalatine foramen" and compared
      with anatomical specimens to verify the dependability of 3D data. METHOD: The
      position, shape, size and their correlational data of sphenopalatine foramen of 5
      cadaver heads (10 sides) in adults fixed with formalin were dissected and
      measured. RESULT: Multi-slice helical CT has more rapid speed of 3D
      reconstruction and clearer imaging. The technique of Shade surface display and
      Volume rendering can give very clear structure of nasal lateral wall
      "sphenopalatine foramen". The 3D data makes no statistic difference with
      anatomical measurement. The 3D data can instruct the clinic directly. CONCLUSION:
      Multi-slice helical CT three-dimensional reconstruction can be used to
      orientation of surgery.

PMID- 15844577
TI  - [Analyze the role of endoscopic operation in the cerebrospinal fluid rhinorrhea
      repair].
AB  - OBJECTIVE: To explore the effect of the different operative methods on the
      results with endoscopy in the cerebrospinal fluid rhinorrhea according to
      different location and different size. METHOD: All clinical records and data were
      studied retrospectively, compare repair measure under different size and
      different location of fistula. RESULT: (1) Size of fistulas: 1 mm x 1 mm - 20 mm
      x 20 mm; (2) Repair methods: 2 cases were repaired by "Bath-plug" method, 10 by
      onlay, 18 by underlay, and 1 by "Button with fascia". CONCLUSION: (1) The
      suitable repair methods were selected according to size and location. Underlay is
      superior to resist intracranial pressure and better for middle size fistula.
      Onlay is simple and fit to small fistula. "Bath-plug" method was more reliable
      for the small-middle size fistula. "Button with fascia" was more suitable to
      large size fistula. (2) Advantages of the endoscopic technique include exact
      identification of the site of the dural tear, excellent field of vision, less
      complication and precise placement of graft.

PMID- 15844578
TI  - [Sorbalgon strips for nasal packing used in 2013 cases of endoscopic sinus
      surgery].
AB  - OBJECTIVE: To summarize the efficacy of Sorbalgon strips used in endoscopic sinus
      surgery (ESS), to explore a better nasal packing materials. METHOD: From Jan.
      2000 to Apr. 2003., 2013 cases with Sorbalgon strips for nasal packing of nasal
      chronic sinusitis and polyps after endoscopic sinus surgery, and compared with
      packing of Aureomycin ointment gauze. The hemostasia effect and nasal cavity
      response were observed. RESULT: Sorbalgon strips had effectiveness at controlling
      hemorrhage in ESS. Comparing with aureomycin ointment gauze, Sorbalgon strips had
      less bleeding when being removed (P < 0.01), and the nasal cavity response was
      gentle (P < 0.01). The packing time with Sorbalgon strip was no more than 24
      hour. No any adverse event was observed. CONCLUSION: Sorbalgon strips are a
      better nasal packing material used in ESS.

PMID- 15844579
TI  - [Observation of the effect of BCG-SPN in FESS perioperative period].
AB  - OBJECTIVE: To observe the therapeutic effect of BCG-SPN and corticosteroid in
      endoscopic perioperative period of chronic rhinitis (CH) and nasal polyps (NP)
      combined with allergic rhinitis (AR) or asthma, and to inquire their immune
      mechanism and find new therapeutic approach. METHOD: Ninety-six patients
      diagnosed of CH and NP combined with AR or asthma were randomly divided into 3
      groups. Group 1 was given 1ml of BCG-SPN intramuscular injection once every two
      days;group 2 was used corticosteroid nasal spray once a day; group III was given
      those two kinds of preparations as above, all for 5 weeks. The morphologic
      transformation of nasal mucosa was observed under endoscope within 6 months.
      RESULT: The rates of efficiency were as follow: group 1 70.97%, 2 73.33%, 3
      90.63%. Statistically, the difference between group 1 and 2 was insignificant;
      while, the difference between group 3 and each of above was significant.
      CONCLUSION: BCG-SPN and corticosteroid nasal spray were both effective in nasal
      mucosa transformation in FESS postoperation for patients with allergic CH and NP;
      moreover, combined usages were better. The mechanism may be that the balance of
      Th1 and Th2 cell subgroup was modulated by different ways, so as to prevent
      allergic effect. Combined therapy provides new approach to deal with these kinds
      of patients.

PMID- 15844580
TI  - [Imaging analysis of the ethmoid roof].
AB  - OBJECTIVE: To discuss the image anatomy characters in the height and contour of
      the ethmoid roof. METHOD: Retrospective review of direct coronal sinus computed
      tomography (CT) scans in 160 patients. The height and contour of the fovea
      ethmoidalis, and the connection modes between ethmoidal roof and cribriform plate
      were examined. When an asymmetry in the height of the fovea ethmoidalis existed,
      this difference was quantified, and the difference between ethmoidal roof and
      cribriform plate was quantified in high type, too. RESULT: In 25 scans (15.63%),
      there was an asymmetry between the height of the fovea ethmoidalis on the right
      and left sides. Of these 25, 13 (52.00%) were lower on the right side. The
      difference between left and right was 2.35 mm. Sixty-two patients (38.75%)
      demonstrated a contour asymmetry with "flattening" of the ethmoid roof on one
      side. Horizontal type was 116 sides (36.25%), and high type was 204 sides
      (63.75%) in the connection modes between ethmoidal roof and cribriform plate. The
      difference was 2.80 mm in the high type. CONCLUSION: There were asymmetries in
      the height and contour of the right and left fovea ethmoidalis. The asymmetry was
      most often the result of a difference in contour with flattening of the fovea on
      one side. The high type was the most connection modes between ethmoidal roof and
      cribriform plate. This underscores the importance of careful preoperative and
      intraoperative review of paranasal sinus CT scans in patients undergoing
      endoscopoic sinus surgery.

PMID- 15844581
TI  - [Clinical assessment of bone scanning in 78 patients with nasopharyngeal
      carcinoma after radiotherapy].
AB  - OBJECTIVE: It is an evaluation of radionuclide bone scanning in detecting bone
      metastasis in the patients with nasopharyngeal carcinoma after radiotherapy.
      METHOD: The bone scanning was performed in 78 patients with nasopharyngeal
      carcinoma after radiotherapy. RESULT: Bone metastasis were detected in 47
      patients out of 78, including 46 squamous cell carcinoma and 1 undifferentiated
      carcinoma. CONCLUSION: Radionuclide bone imaging is useful for diagnosing,
      treating and prognosing of nasopharyngeal carcinoma.

PMID- 15844582
TI  - [Surgical analysis of sinonasal inverting papilloma with recurrence].
AB  - OBJECTIVE: To investigate the effectiveness of intranasal endoscopic surgery of
      sinonasal inverting papilloma with recurrence. METHOD: Retrospective comparative
      analysis of intranasal endoscopic surgery on 7 patients and lateral rhinotomy on
      14 patients of sinonasal inverting papilloma with recurrence. RESULT: All the 21
      cases with recurrence had suffered sinonasal surgery such as lateral rhinotomy,
      endoscopic surgery, intranasal surgery, Caldwell-Luc operation and nasal
      polypectomy. Among them, 14 cases recurred once, 4 cases recurred 2 times, 2
      cases recurred 3 times and 1 case recurred 5 times. The recurrence time ranged
      from 1 month to 12 years, and the mean time was 20 months. There was no
      recurrence both in 7 patients with intranasal endoscopic surgery during 1-3
      years' follow-up and in 14 patients with lateral rhinotomy during 1-10 years'
      follow-up. CONCLUSION: The intranasal endoscopic surgery is an effective
      management for sinonasal inverting papilloma with recurrence.

PMID- 15844583
TI  - [Clinical anatomy study of olfaction correlative nerves].
AB  - OBJECTIVE: To find out the relation of the olfactory nerves, the optic nerve, and
      the nasal sinuses. Provide anatomic data for not to damnify olfactory nerves in
      the surgery. METHOD: To measure the olfactory nerves, the olfactory bulb, and
      olfactory tract on 16 adult cadaveric specimens, and observe the relation of the
      olfactory nerves, the optic nerve,and the nasal sinuses. RESULT: Length of the
      olfactory tract was (29.32 +/- 2.11) mm, width of the olfactory tract was (3.36
      +/- 0.83) mm. The distance from the midpoint of the olfactory tract to the
      midline of the skull was (5.48 +/- 1.02) mm. The angle between olfactory tract
      and midline of the skull was (21.32 +/- 3.28) degrees. Length of the olfactory
      bulb was (10.43 +/- 2.35) mm, width of the olfactory bulb was (5.12 +/- 0.62) mm.
      27/32 olfactory tracts were border upon with sphenoid sinus and ethmoid sinus,
      3/32 olfactory tracts were border upon with ethmoid sinus, 2/32 olfactory tracts
      were border upon with frontal sinus. All olfactory tracts crossed the optic nerve
      at the internal meatus of optic nerve canal. The olfactory bulb and ethmoid bulb
      were on equal line. CONCLUSION: Almost all olfactory tracts were lied in the
      inboard of the orbital cavity, protect the roof of the nasal sinus to avoid
      damnify the olfactory nerves. It is easy to pull out the olfactory nerves when
      raising the cerebra in the operation of anterior cranial fossae.

PMID- 15844584
TI  - [Expression of eotaxin gene in nasal mucosa of allergic rhinitis in the guinea
      pig sensitized by fungal allergen].
AB  - OBJECTIVE: To study the expression and significance of Eotaxin gene in nasal
      mucosa of guinea pig sensitized by fungal allergen. METHOD: Alternaria alternata
      sensitized guinea pigs used as animal model of allergic rhinitis (AR). The
      changes in the nasal mucosa were studied by pathological method and the Eotaxin
      gene were studied by In Situ Hybridization. RESULT: The behavior science score of
      experimental group was significant higher than the controls group. Plenty
      eosinophils were found in lamina propria of nasal mucosa of experimental group.
      Eotaxin gene is expressed in lamina propria of nasal mucosa of experimental
      group. The controls group had not positive expression. CONCLUSION: Eotaxin gene
      is expressed at high levels in nasal mucosa of fungal allergic rhinitis in the
      guinea pig. Plenty eosinophils were found in nasal mucosa. We considered that
      Eotaxin gene and eosinophils could play a key role in fungal allergic rhinitis.

PMID- 15844585
TI  - [Preliminary clinical study of fubiding in treatment of perennial allergic
      rhinitis].
AB  - OBJECTIVE: To observe therapeutic effect and adverse reaction of Fubiding
      (Desloratadine tablets) in treatment of perennial allergic rhinitis (PAR).
      METHOD: One hundred and fifty PAR patients were confer five milligram Fubiding
      everyday by mouth, in series 30 days. To detain to use etc's allergic medicine or
      naristillae. RESULT: All cases were visited a year, the 109 examples of show were
      excellence (72.67%), 34 cases were effectively (22.67%), 7 examples were nullity
      (4.67%). The gross is efficient to attain 95.34%. And the adverse effects were
      slightly. CONCLUSION: Fubiding in treatment PAR has the curative effect shows
      excellence, the adverse effects were slightly etc. advantage. The worthy of
      clinical expansion is applied.

PMID- 15844586
TI  - [Longitudinal gracilis musculocutaneous flaps with a crossing boundary blood
      supply from the obturator artery].
AB  - OBJECTIVE: The traditional gracilis musculocutaneous flap is supplied by a branch
      of deep femoral artery, which enters the muscle in between the upper and middle
      third of it. So the flap barely reaches the pelvis and perineum region for
      reconstruction. By exploring the blood supply pattern we tried to rotate the flap
      Upon at the higher point starting at the obturator foramen in order to let it
      cover a bigger area. METHODS: anatomical reviewing of the blood supply of the
      gracilis branches of obturator, medial femoral circumflex and deep femoral
      arteries. Based on this a new type of longitudinal gracilis musculocutaneous flap
      supported only by the obturator artery was designed to reach the pelvis, female
      genitalia, pubic symphysis, inguinal area easily. RESULTS: The new kind of flap
      has been applied to 9 patients for deformity repairing and tissue replacement in
      the pelvic and perineal area. All the flaps survived and achieved satisfactory
      result with 3 months to 3 years' follow up. CONCLUSIONS: Longitudinal gracilis
      musculocutaneous flaps supplied by the obturator artery can be used as regular
      musculocutaneous flap clinically.

PMID- 15844587
TI  - [The application of forward and reversal flow axial island flap based on the
      superficial temporal artery in the orbital skin defects].
AB  - OBJECTIVE: To investigate the application of forward and reversal flow axial
      island flap in the orbital skin defects. METHODS: According to the distribution
      of superficial temporal artery as well as the anastomoses with the branches of
      supraorbital artery and supratrochlear artery, etc, the frontal, scalp,
      preauricular and postauricular island flaps were designed. The flaps were
      displaced through subcutaneous tunnel to cover all kinds of orbital skin defects.
      RESULTS: 13 cases of forward flow flap and 9 of reversal flow flap out of 22
      cases in all were observed. One postauricular reversal flow axial island flap
      showed the obstruction of venous refluence in early postoperative stage, however,
      after active treatment, mere the distal epidermal necrosis was revealed. There
      were six re-operations on the postoperative flap hypertrophy. The others were in
      good shape and functional state. CONCLUSIONS: The superficial temporal artery is
      one of most vital blood supply in the upper face. It has wide anastomoses with
      the supraorbital artery and supratrochlear artery. As the colors and the nature
      of the frontal, preauricular and post auricular skin are close to orbital skin,
      the application of forward and reversal flow axial island flap based on the
      superficial temporal artery can be used in the reconstruction of all kinds of
      orbital skin defects.

PMID- 15844588
TI  - [Repair of the soft tissue defect of the fifth finger with a reversed ulnar
      fasciocutaneous flap from the fifth metacarpal side].
AB  - OBJECTIVE: To introduce a method by reversed ulnar fasciocutaneous flap incised
      form the ulnar side of the fifth metacarpal area for repairing the soft tissue
      defect of the fifth finger. METHODS: From May 2001 to September 2001, ten
      patients with the soft tissue defects of the thenar side, dorsal side or ulnar
      side of the fifth finger were treated with the reversed ulnar fasciocutaneous
      flap incised from the fifth metacarpal area. The axial line of the flap was the
      line from ulnar side of the head of the fifth metacarpal bone to the pisiform
      level. The revolving point of the flap pedicle was 0.5-1 cm near the proximal end
      of the metacarpal-phalangeal joint.The area of the flap was form 5.0 cm x 3.5 cm
      to 1.5 cm x 1.0 cm. RESULTS: All flaps of the ten cases were alive. 5-7 months
      followed-up show that, after operation, the flap present sensation in 6-12 mm,
      with soft texture and good appearances. CONCLUSIONS: The advantages of this
      operative method were as follows: the reversed ulnar fasciocutaneous flap of the
      fifth metacarpal area have reliable blood supply, it was easily dissected and
      with good texture. So far this kind of flap is a good choice in repairing the
      soft tissue of the fifth finger.

PMID- 15844589
TI  - [Repair of soft-tissue defects of feet and ankles by using an expanded reverse
      island flap with a saphenous neuro-vascular pedicle].
AB  - OBJECTIVE: To evaluate a expanded reverse island flap with a saphenous neuro
      vascular pedicle for repairing the defects of the feet and ankles. METHODS: An
      expanded reverse island skin flap, with the Six saphenous neuro-vascular pedicle,
      was designed to repair the skin defects on the feet and ankles. RESULTS: patients
      with the defects of the feet and ankles were treated with the expanded saphenous
      island flap and all of the The expanded reversed island skin flaps were survived.
      The largest flap size was 12 cm x 10 cm. CONCLUSIONS: flap could be a good option
      for repairing the defects of the feet and ankles.

PMID- 15844590
TI  - [Twice delaying of the expanded flap].
AB  - OBJECTIVE: To introduce a new method for enlarging the survival area of an
      expanded flap. METHODS: After the skin expander was inflated with enough
      injection, the first delaying was performed. In the operation, two incisions were
      made in the skin and subcutaneous tissue superficial to the expander capsule on
      both sides of the long axis of the expanded flap. After 10 to 14 days, the second
      delaying followed, in which one pedicle was divided to form a unilateral
      pedicled, super-long random flap. When the flap was transferred to the recipient
      Since 2000,this technique has been used in 16 patients. All the area, the door
      site was closed directly. RESULTS: flaps survived completely. CONCLUSIONS: The
      technique of twice delaying can enlarge the survival area of the expanded skin
      flap.

PMID- 15844591
TI  - [Distraction osteogenesis in patients with syndromic midface retrusion--a primary
      experience].
AB  - OBJECTIVE: To study the feasibility of midface distraction for correction of
      severe syndromic Four consecutive patients with severe syndromic midface
      retrusion underwent midface retrusion. METHODS: distraction osteogenesis. The
      patients(three girls and one boy) aged from 4 to 12 years. Two were with Crouzon
      syndrome, one with Apert and one with Marfan syndrome. One was treated with Le
      Fort III external distraction, two with Le Fort III internal distraction, and the
      other with monobloc internal distraction. The distraction devices were activated
      on the fourth postoperative day at 1 mm per day. RESULTS: All patients completed
      the distraction as activated on the fourth postoperative day at 1 mm per day.
      Results was planned. Successful advancement of 8 to 20 mm was obtained at the
      occlusal level in all patients as measured by cephalograms. The facial appearance
      was significantly improved,especially in the orbits and the upper part of the
      nose. Follow-up from 4 months to one year demonstrated that the face was
      symmetrical. All patients obtained This study shows that although midface
      distraction osteogenesis needs to be satisfactory results. CONCLUSIONS: This
      study shows that although midface distraction osteogenesis needs to be improved
      to increase its controllability, it has obvious advantages over the traditional
      way of bone graft and rigid fixation. Midface distraction avoids bone grafts and
      alleviates the restriction of the soft tissue to midfacial bone advancement.
      Midface distraction osteogenesis is an effective and practical way to correct
      severe syndromic midfacial hypoplasia.

PMID- 15844592
TI  - [Intraoral curved osteotomy for malar reduction].
AB  - OBJECTIVE: To present a new method for reduction of the prominent malar complex
      by using the curved osteotomy through intraoral incision. METHODS: According to
      the anatomical characteristics of the malar complex, a new curved osteotomy was
      designed for reduction of the prominent malar complex. This method, that made
      malar arch move toward backside, inside and upside, lowered the whole malar
      complex and gain better contour of malar area. RESULTS: From 2001 to 2003, 41
      patients were treated with the intraoral curved osteotomy [for reduction of the
      prominent malar complex. All patients obtained good results. CONCLUSIONS: Through
      the intraoral approach, the curved osteotomy method could lower the whole
      prominent malar complex and get better contour of malar area.Intraoral curved
      osteotomy for reduction of the prominent malar complex could be an ideal method
      with better face contour, simpler technique, and fewer complications.

PMID- 15844593
TI  - [An experimental study on the influence of osteoporosis to bone repairing with
      bone matrix gelatin in ovariectomized rats].
AB  - OBJECTIVE: To study the influence of experimentally osteoporosis to osteogenic
      efficiency of bone matrix gelatin(BMG) implanted into the calvarial defects of
      rats. METHODS: Sixty-eight female SD rats of 12 +/- 1 weeks were randomly divided
      into two groups with 34 rats in each group. The ovaries were excised in the
      ovariectomized group (VG). The control group underwent sham surgery. Ninety days
      after ovariectomy, 10 rats from each group were examined to ensure the formation
      of postmenopausal osteoporosis by measuring bone density of the femur with single
      photon absorptiometric measurements. A critical-sized (8 mm in diameter)
      calvarial defect was created on the rest of 48 rats. Bone matrix gelatin was
      implanted to the defect. The rats were scarified at the 21st and 56th day after
      surgery respectively. The new bone forming capability of BMG was evaluated with
      undecalcified histological observation, tetracycline fluorescence marker,
      quantitative bone histomorphometry, At 90th day after ovariectomy, bone density
      of scanning electron microscopy and X-ray spectrometry. RESULTS: OVG showed very
      significant difference compared with the control group (0.315 +/-.015) g/cm2 vs
      [(0.347 +/- 0.017) g/cm2, P < 0.01 ]. At the 21st day following the implantation
      operation, new bone formed within the bone defects in both groups. The amount of
      new bone in OVG was lower than the control group. The tetracycline-labeled region
      in the bone defect was sparser in the OVG. At the 56th day, the bone defects
      healed mostly in the control group but fibrous tissue filled parts of bone defect
      in the OVG. The distance between two fluorescent lines of incorporated
      tetracycline and the mean mineralization deposition were significantly lower in
      the OVG than the control at the 21st day and 56th day. Mineralization of callus
      in OVG was inferior. Significant difference was found between the OVG and the
      control group in the calcium to phosphate ratio of callus in bone defects at the
      two time-points. CONCLUSIONS: Experimentally induced osteoporosis depressed
      osteogenic efficiency of BMG, suggesting that estrogen could play an important
      role in bone remodeling with bone substitute participating.

PMID- 15844594
TI  - [Chromosomal aberration in human keloid analyzed by comparative genomic
      hybridization].
AB  - OBJECTIVE: To identify the genetic alteration in human keloid. METHODS:
      Comparative genomic hybridization was applied in 6 cases of keloid to investigate
      the genomic imbalance (the gain or loss of genetic material). RESULTS: The study
      showed that the loss of chromosome DNA copies included chromosome,
      1,7,9,13,16,17,18,19,20,22. Among them, the frequently detected chromosome loss
      was chromosome 1 p(66.7%), 16 (83.3%), 20 (83.3%) and 22 (83.3%). The minimum
      overlapping regions were 1 pter-32.2,16p13.2p11.l,20q11.1-q13.2 and 16p13.2
      p11.1. Frequent gain of DNA copy numbers was not found in the special regions.
      CONCLUSIONS: The mapping of DNA copy variation frequency in keloid showed that
      there may be inhibitory genes in chromosomes 1p,16,20,22. The loss of these genes
      may be involved in the development and progress of keloid.

PMID- 15844595
TI  - [Investigation of p53 polymorphism for genetic predisposition of keloid and
      hypertrophic scar].
AB  - OBJECTIVE: To investigate the codon-72 polymorphism of the tumor suppressor gene
      p53, codon-72 encodes arginine (Arg) or proline (Pro) for a genetic
      predisposition,to keloid or hypertrophic scar. METHODS: The distribution of codon
      72 polymorphism of p53 gene was analyzed from the 54 keloid and 30 hypertrophic
      scar(HS)of the Japanese patients with restriction fragment length polymorphism
      analysis and DNA sequence analysis. RESULTS: The frequency of the Proline
      encoding alleles and Arginine-encoding alleles in the hypertrophic scar patients
      and the piercing-induced ear-lobe keloid patients, was deviated significantly
      from that in the normal Japanese controls. CONCLUSIONS: The Proline-encoding
      allele and Arginine-encoding allele could have the risks for the hypertrophic
      scar and the piecing-induced ear-lobe keloid. Also, the pathogenesis of the
      hypertrophic scar seems to be different from that of keloid at the molecular
      level.

PMID- 15844596
TI  - [Signal roles of protein tyrosine kinase in transforming growth factor-beta1, or
      interferon-gamma regulated proliferation and collagen synthesis by fibroblasts
      from hypertrophic scar and normal dermis].
AB  - OBJECTIVE: To study the signal roles of protein tyrosine kinase (PTK) on
      proliferation and collagen synthesis of fibroblasts derived from hypertrophic
      scar(HS-FB) and normal skin (NS-FB) by interferon-gamma (IFN-gamma) or
      transforming growth factor beta1 (TGF-beta1). METHODS: HS-FB and NS-FB were
      cultured and passaged in Dulbecco's modified Eagle's medium(DMEM). The PTK
      activity in unstimulated or IFN-gamma or TGF-beta1-stimulated HS-FB and NS-FB
      (10,30,60 and 120 min) were assayed by phosphorus (32P) incorporation. Cell
      proliferation was determined with MTT stain. The type III procollagen was
      measured by radioimmunoassay. RESULTS: TGF-beta1 did not change PTK activity but
      it increased predominately proliferation and collagen synthesis of HS-FB and NS
      FB in time-dependent fashion. Genistein, an inhibitor of PTK, inhibited HS-FB and
      NS-FB to proliferate and synthesize collagen but it could not change the roles on
      proliferation and collagen synthesis by TGF-beta1. IFN-gamma activated
      transiently PTK (P < 0.05) and increased proliferation and collagen synthesis of
      both fibroblast (P < 0.05, at 30 min, 60 min). As the recovery of PTK activity,
      the proliferation and collagen synthesis were inhibited by IFN-gamma at 120 min.
      Furthermore, Genistein abrogated the transient increased roles and partly
      reversed the longterm inhibitory functions by IFN-gamma (P < 0.05) . There were
      no difference on PTK activity, proliferation and collagen synthesis between HS-FB
      and NS-FB. CONCLUSIONS: PTK did not mediate the signal of TGF-beta1 but
      transduced the signal of transient increased roles of IFN-gamma. Inhibited or
      activated PTK might mediate the signal of decreasing or increasing proliferation
      and collagen synthesis of fibroblast.

PMID- 15844597
TI  - [The expression of tenascin-C mRNA in keloids and hypertrophic scars].
AB  - OBJECTIVE: To investigate the expression of Tenascin-C mRNA in keloids and
      hypertrophic Total RNA was isolated from normal adult skin. A cDNA fragment (base
      5941-6481bp) of the scars. METHODS: full-length human Tenascin-C cDNA was
      synthesized by polymerase chain reaction and subcloned in pGEM-T-easy. Dioxygen
      labeled anti-sense and sense probes were synthesized by using a Sp6/T7 RNA
      synthesis kit in the present of Dig-UTP in vitro. The samples were taken from
      keloids in 10, hypertrophic scars in 10 and normal adult skin in 5. The
      hybridization was performed with 4% paraformaldehyde-fixed and wax-embedded
      sections to detect the Tenascin-C mRNA. RESULTS: The Tenascin-C mRNA was negative
      in the normal adult epidermis and weakly located in the fibroblasts of the
      papillary dermis and the epidermal adnexa. In all of the 10 keloid specimens, the
      Tenascin-C mRNA was positive throughout the epidermis and widely distributed in
      the dermis included in the fibroblasts, endothelial cells and epidermal adnexa.
      In the specimens of the 3 hypertrophic scars,the Tenascin-C mRNA was also
      positive in the epidermis, but in the other 7 cases, it became negative. In the
      dermis of the hypertrophic scar,the Tenascin-C mRNA was weaker than that in the
      keloid, but stronger than that in the normal skin. CONCLUSIONS: The expression of
      Tenascin-C mRNA is markedly enhanced in the keloids.

PMID- 15844598
TI  - [Anatomic observation of inferior gluteal artery].
AB  - OBJECTIVE: Observe the course,distribution and variation of inferior gluteal
      artery to provide an anatomic basis. METHODS: 18 specimen (11 male and 7 female.
      9 left and 9 right) were perfused with red latex to show inferior gluteal
      arteries and the tissue around them. RESULTS: Usually inferior gluteal artery
      travels through infrapiriform foramen and goes down along ischiadicus nerve. It
      gives three main branches as ramus of articularis, ramus of ischiadicus, ramus of
      muscularis at average distances of 17.3 mm, 33.2 mm and 51.8 mm to infrapiriform
      foramen and nourishes them respectively. However, variation was found in 7 of 18
      specimen (5 are female) . CONCLUSIONS: The course of inferior gluteal artery is
      steady in most cases, but sometimes variation can be found. Special examinations
      such as colour Doppler ultrasound are suggested to find the course of inferior
      gluteal artery on the whole level before operation.

PMID- 15844599
TI  - [The expression of p73 and c-fos protein in hemangioma and its significance].
AB  - OBJECTIVE: To investigate the expression of p73 and c-fos protein and its
      significance in the development of children hemangioma. METHODS: The quantitative
      expressions of p73 and c-fos protein in hemangioma and normal skin were detected
      by immunohistochemistry. RESULTS: The expressions of p73 and c-fos protein were
      strong in proliferative hemangioma while they were very weak in involutional
      hemangioma and normal skin. There were significant differences between the
      proliferative and involutional hemangioma or the normal skin in the expressions
      of p73 and c-fos (P < 0.01). No statistical significances of p73 or c-fos P73
      expressions were observed between involutional hemangioma and normal skin (P >
      0.05). CONCLUSIONS: P73 and c-fos may play an important role in the development
      and involution of skin hemangioma.

PMID- 15844600
TI  - [Bacteriology study of hypospadias].
AB  - OBJECTIVE: This clinical study was to explore why the neo-urethra is liable to be
      infected after hypospadias operation, find the source and the common floras of
      infection, and accordingly, improve the peroperation procedures so as to reduce
      postoperative infection rate. METHODS: The pathogenic floras were examined and
      analyzed by germiculture and karyotype analysis. RESULTS: The bacteria in the neo
      urethra mostly came from the orifice and the reconstruction material of the
      urethra. The most common floras that caused infection were gram-positive coccus.
      The most sensitive antibiotics for hypospadias infection were demethylvancomycin.
      CONCLUSION: The postoperative infection of hypospadias is incisional, not the
      urinary system infection. Because the microenvironment of the neo-urethra is more
      suitable for infection than that of the skin or mucosa, the reconstructed urethra
      is likely to be infected.

PMID- 15844601
TI  - [An experimental study on repair of peripheral nerve injury by transplantation of
      microcapsulated NGF-expressing NIH 3T3 cells].
AB  - OBJECTIVE: To investigate the feasibility of promoting nerve regeneration by
      using microcapsulated NGF-expressing cells transplantation. METHODS: The plasmid
      pcDNA3. 1 + /NGF, containing rat NGF gene, was transfected into the NIH 3T3 cell
      by using FuGENE6 transfection reagent. The genetically modified cells expressing
      NGF gene were enclosed within the alginate-polylysine-alginate (APA)
      microcapsules and then cultured in vitro. The growth and NGF secretion of the
      cells were measured periodically. At the same time, these microcapsulated NGF
      expressing cells were transplanted into the injured sciatic nerve. The
      regeneration and functional recovery of the nerve were evaluated in 4 weeks, 8
      weeks and 12 weeks after the operation. RESULTS: The microcapsulated cells had
      survived and secreted the NGF in three months in vitro. In the group with
      microcapsulated NGF-expressing cells, the number of the regenerated axons was in
      large and the nerve fibers were arranged regularly. Compared to other groups,
      there was less scar , edema and monocytes found at the stoma in the goup. The
      moter nerve conductive velocity, nerve muscle-action potential and SFI were
      improved. CONCLUSIONS: The microcapsulated NGF-expressing cells could
      significantly enhance the nerve regeneration and reduce inflammatory response of
      xenograft.

PMID- 15844602
TI  - [The effect of pcDNA 3.1/RPs15 on skin fibroblasts in vitro].
AB  - OBJECTIVE: To construct eukaryotic expression vector of ribosomal protein
      sl5(RPs15) gene and study its effect on mouse skin fibroblasts in vitro. METHODS:
      The RPs15 cDNA encoding region of fetal mouse skin was amplified by reverse
      transcription-polymerase chain reaction (RT-PCR) method and cloned into
      eukaryotic expression vector pcDNA3.1(-). The recombinant plasmid was transfected
      into adult mouse skin fibroblasts by FuGENE6 transfection reagents. Then the
      expression of RPs15 gene, was detected and its biological effect on fibroblasts
      was measured. RESULTS: The DNA sequencing result of pcDNA3.1/RPs15 was identical
      with the reported. The RPs15 gene was expressed in transfected fibroblasts. The
      growth density of fibroblasts decreased with the conformation changing
      accordingly. CONCLUSIONS: The eukaryotic expression vector pcDNA3.1/RPs15 is
      successively constructed and can be expressed in mouse skin fibroblasts. The
      results set up a basis for further study of the effect of RPs15 gene on skin
      fibroblasts.

PMID- 15844603
TI  - [Rabbit urethral defect repair with freeze-dried acellular bladder submucosa].
AB  - OBJECTIVE: To evaluate the result of urethral defect repair using freeze-dried
      acellular bladder submucosa. METHODS: The freeze-dried acellular bladder
      submucosa was obtained from human cadaveric bladder submucosa using freeze-thawed
      enzymatic treatment and the freeze-drying technique. 18 male New Zealand rabbits
      were used in this experiment. A defect of 1.0 cm x 0.5 cm was created in the
      ventral urethra of the animal. The acellular matrix was grafted to the urethral
      defect in 14 rabbits. The other 4 animals underwent a sham operation as the
      controls. From postoperative one to twenty-four weeks, the animals underwent
      retrograde urethrography at certain intervals. The grafts of the acellular matrix
      were taken and prepared for histological evaluation. RESULTS: No obvious urethral
      stricture was observed in the 14 matrix-grafted animals. Histological
      examinations of the specimens showed progressive infiltration of cells and
      vascular vessels. Complete epithelization was obtained at 2 weeks. The
      orientation of collagen fibers in the matrix-grafted area tended to be regular
      with time. CONCLUSIONS: Freeze-dried acellular bladder submucosa may be a
      suitable material for urethral defect repair, which induces urethral mucous cells
      to migrate, grow and epithelialize.

PMID- 15844604
TI  - [The expression of p21(WAF1/CIP1) and PCNA in hypopharyngeal and laryngeal
      squamous cell carcinomas].
AB  - OBJECTIVE: ln order to evaluate the significance of the expression of
      p21(WAF1/CIP1) and PCNA (proliferating cell nuclear antigen) in hypopharyngeal
      and laryngeal squamous cell carcinoma. METHOD: Ninety-three patients who accepted
      operations for hypopharyngeal and laryngeal squamous cell carcinoma from 1998 to
      2003 were included in this study, 45 cases were hypopharyngeal cancer, 25 cases
      were supraglottic cancer, 23 cases were glottic cancer. The clinical and
      histopathological features of these patients were reviewed. The Envision
      immunohistochemistry method was utilized to stain these faculties. RESULT: The
      expression of p21(WAF1/CIP1) had no correlate with differentiation, N stage,
      metastasis, survival, recurrence and laryngeal site of involvement. However,
      significantly correlated with T stage of hypopharyngeal and laryngeal squamous
      cell carcinoma, also correlated with prognosis of hypopharyngeal and laryngeal
      squamous cell carcinoma. The percentage of PCNA labeled cells showed the
      statistically significant with clinical and N stage, but no significance was
      found among other clinicopathological parameter and PCNA staining intensity.
      CONCLUSION: p21(WAF1/CIP1), PCNA play important roles in the progression of
      hypopharyngeal and laryngeal squamous cell carcinoma and are possible prognostic
      discriminators in hypopharyngeal and laryngeal squamous cell carcinoma.

PMID- 15844605
TI  - [Extraluminal foreign body originated from pharynx and esophagus (24 cases
      report)].
AB  - OBJECTIVE: To summarize the symptoms, various diagnostic procedures, and therapy
      of extraluminal foreign body originated from pharynx and esophagus (EFBOPE).
      METHOD: Twenty-four patients with EFBOPE were retrospectively reviewed. RESULT:
      Twenty-two cases were removed surgically, 1 case was spontaneous expulsion, 1
      case died. CONCLUSION: EFBOPE is seldom seen in the clinical, diagnosis of EFBOPE
      should be considered whenever haematemesis or haemorrhage, inflammation or
      abscess in parapharyngeal space outside of pharynx and esophagus are presented
      after ingesting foreign body. Radiography and computed tomography are main
      diagnostic tools. Surgical treatment is the only effective method for EFBOPE and
      must be performed in time.

PMID- 15844606
TI  - [The application of the temporalis myofacial flap in the reconstruction of
      craniofacial oncologic defects].
AB  - OBJECTIVE: To explore the application of the temporalis myofacial flap(TMF) in
      the reconstruction of craniofacial oncologic defects. METHOD: Ten cases with
      craniofacial neoplasms were treated surgically using TMF to reconstruct oncologic
      defects. TMF during 2000-2003. was used to reconstruct cranial base in 3 cases,
      oropharynx in 5 cases and orbital defects in 2 cases. TMF was designed according
      to size and locus of defect. The sizes of the flaps ranged from 3 cm x 4 cm to 8
      cm x 10 cm. RESULT: During follow-up of 8 to 50 months, there were no cases of
      flap loss, no cranial infection or cerebrospinal fluid leak in cranial base
      reconstructions, no speech or swallowing disturbance in oropharyx reconstruction.
      All patients were satisfied with appearance with orbital reconstruction.
      CONCLUSION: TMF is a useful and reliable flap for reconstruct the craniofacial
      oncologic defects.

PMID- 15844607
TI  - [Quantitative evaluation of the upper airway by CT scan with the Muller
      maneuver].
AB  - OBJECTIVE: To explore the quantitative evaluation of upper airway by CT scan with
      Muller maneuver, and study the difference of the pharynx wall resilience between
      OSAHS patients and normal adults. METHOD: Twenty-five patients with OSAHS and 20
      normal adults were included in the study. CT evaluated the upper airway from roof
      of nasopharynx to glottis with the use of a Phlips Tomoscan AV Expander E1 spiral
      scanner. The cross section area and the dimension of palate, uvula, lingua and
      epiglottis region upper airway were studied. Then repeated the same scan process
      when testee play-ed Muller maneuver, and calculated the total pharynx wall
      resilience (TPWR), lateral pharynx wall resilience (LPWR) and anterior post
      pharynx wall resilience (APPWR) of different levels of upper airway. RESULT:
      Between OSAHS patients and normal adults, there are obviously difference in the
      TPWR and LPWR of palate, uvula, lingua region upper airway, and no difference in
      epiglottis region upper airway. There are obviously difference in the APPWR of
      palate and uvula region upper airway, and no difference in lingua and epiglottis
      region upper airways. The LPWR is much more than APPWR in all four level of upper
      airway in both OSAHS patients and normal adults. CONCLUSION: The study suggest
      that we can get quantitative data of upper airways by CT scan. And there are
      obviously TPWR, LPWR and APPWR difference at different levels of upper airway
      between OSAHS patients and normal adult, the increasing of TPWR, LPWR and APPWR
      is one etiology of OSAHS.

PMID- 15844608
TI  - [Anatomic characteristics and relationship of lingual artery and hypoglossal
      nerve with tongue base].
AB  - OBJECTIVE: To investigate the anatomic characteristics of lingual artery and
      hypoglossal nerve and relationship between lingual artery and hypoglossal nerve
      in tongue base, for the purpose of improving data with clinic and increasing
      safety in the operation of tongue base. METHOD: Twenty extraoral dissections of
      the submandibular region were performed on 10 human cadavers. The origin and
      distribution of lingual artery and hypoglossal nerve were observed: (1) The
      lingual artery was divided into four segments, length and adjacent organs were
      observed and measured; (2) The hypoglossal nerve length and adjacent organs were
      observed and measured; (3) The anatomic relationship of lingual artery and
      hypoglossal nerve was observed and measured. RESULT: The whole length of lingual
      artery was (9.73 +/- 0.83)cm. At points of foramen cecum of the tongue, 1 cm
      prior to foramen cecum, 1 cm behind foramen cecum and at adjacent part of foramen
      cecum to lateral tongue, hyoid, and distances between lingual artery and lateral
      of the tongue were separately measured. The distances were (2.34 +/- 0.20) cm,
      (2.48 +/- 0.14) cm, (2.43 +/- 0.26) cm, (2.53 +/- 0.33) cm, (2.14 +/- 0.16) cm,
      (1.11 +/- 0.09) cm, respectively. At points of foramen cecum of the tongue, 1 cm
      prior to foramen cecum, 1 cm behind foramen cecum and at adjacent part of hyoid,
      lateral tongue, and distance between hypoglossal nerve and midline of the inner
      mandible were separately measured. The distances were(2.28 +/- 0.14) cm, (2.36 +/
      0.16) cm, (2.34 +/- 0.21 ) cm, (1.25 +/- 0.42) cm, (1.86 +/- 0.32) cm, (2.64 +/-
      0.28) cm, respectively. The position of the tongue base, lingual artery and
      hypoglossal nerve are significantly inferior and lateral, that is, 2 cm inferior
      and (1.11 +/- 0.09) cm lateral to the foramen cecum; (2.08 +/- 0.33) cm medial to
      the inner mandible. CONCLUSION: This inferior lateral location-'V' type- allows
      the potential for aggression tongue base resection without neurovascular bundle
      compromise. To ensure the operating safety, the depth and angle of radiofrequency
      of the tongue base for OSAHS should be controlled.

PMID- 15844609
TI  - [Anatomic study on the recurrent laryngeal nerve in thyroid surgery].
AB  - OBJECTIVE: To study the anatomic characteristic and dissecting approach of
      recurrent laryngeal nerve in thyroid surgery. METHOD: A retrospective review of
      surgical data of consecutive 56 patients undertook thyroid surgery was conducted,
      in which total 63 recurrent laryngeal nerves were identified. RESULT: A nerve
      bifurcation was found in 48 recurrent laryngeal nerves. Twenty-nine nerves were
      deep to the inferior thyroid artery, 19 were superficial to the artery, 8 were
      between the arteries. The inferior thyroid artery was not found in 7 cases.
      CONCLUSION: Correct identification and safe dissection of the recurrent laryngeal
      nerve are essential in thyroid surgery.

PMID- 15844610
TI  - [Polysomnography analysis in children].
AB  - OBJECTIVE: To analyze the characteristics of Polysomnography (PSG) in children
      with obstructive sleep apnea-hypopnea syndrome(OSAHS). METHOD: Forty-five
      children with sleep breathing disorder were studied with 32 guide PSG and
      analyzed by Polysmith. PSG results of OSAHS children were compared with primary
      snore group. RESULT: The mean age of OSAHS children was(7.3 +/- 3.8) years and
      the mean body weight was (40.1 +/- 19.7) kg. The mean value of NREM stage 1,
      stage 2, stage 3+4 and REM stage was(21.4 +/- 13.2)%, (43.1 +/- 13.7)%, (26.1 +/-
      14.0) % and (9.4 +/- 6.0) % respectively. The sleep structure between OSAHS group
      and primary snore group was not significant (P > 0.05). The mean value of AHI of
      OSAHS children was(12.8 +/- 8.1) h. AI was (6.7 +/-6.6)h, HI was(6.1 +/- 5.1)h.
      CONCLUSION: The sleep structure of children is prefect and mild effected by
      OSAHS.

PMID- 15844611
TI  - [Effects of intervention embolization therapy and intratumor injection with
      hardener on head and neck gigantic hemangioma].
AB  - OBJECTIVE: The goal of this study is to present our experience of transarterial
      embolization and intratumor injection for the treatment of gigantic hemangioma of
      the head, face, and neck. METHOD: From 2001 to 2003, 3 patients with gigantic
      hemangioma were selected to get digital subtraction angiography (DSA) and
      transarterial embolization and intratumor injection successfully. RESULT:
      Angiography after embolization showed almost complete obliteration of hemangioma.
      There were no serious complications such as embolism to other organs and necrosis
      of a large area in the embolized tissue. Only slight swelling and pain in the
      embolized area were present. And gradually disappeared by expect and treatment.
      No recurrence of the symptoms was occurred in a follow-up evaluation of 6- 24
      months. CONCLUSION: Using of DSA. transarterial embolization and intratumor
      injection showed an excellent clinic effect on treatment of hemangioma, reducing
      the recurrence of the symptoms.

PMID- 15844612
TI  - [The voice analysis of subtotal laryngectomy by pedicled flaps reconstruction of
      vocal cord].
AB  - OBJECTIVE: To compare the voice quality of patient's after surgery over one year
      between the reconstruction of laryngeal function in subtotal laryngectomy by
      pedicled flaps and other laryngeal function in subtotal laryngectomy. METHOD: By
      using Dr Speech's acoustic analysis software, the noise level of the testing room
      was controlled under 45 dB. Before testing, patients have pronounced training.
      The testing voice was selected as[ae]. The evaluation parameters were jitter,
      shimmer, and NNE. RESULT: All the acoustic parameters of the reconstruction of
      laryngeal function in subtotal laryngectomy by pedicled flaps were increased
      distinctly than normal. There were statistical significant differences; compared
      with those by subtotal laryngectomy, the parameters decreased distinctly, and the
      voice quality improved distinctly. CONCLUSION: The reconstruction of laryngeal
      function in subtotal laryngectomy by pedicled flaps improve the voice quality,
      the acoustic analysis can be a measurable data of the postoperative voice quality
      evaluation, and administer to its objective evaluation.

PMID- 15844613
TI  - [The expressions of survivin in squamous cell carcinoma of larynx and its
      clinical significance].
AB  - OBJECTIVE: To investigate the expressions of Survivin in squamous cell carcinoma
      of larynx (SCCL) and the correlation between Survivin and survival time. METHOD:
      The expressions of Survivin in SCCL tissues of 40 cases and normal larynx tissues
      of 5 cases were studied by immunohistochemical staining and quantitative analysis
      of image. RESULT: The expressions of Survivin in SCCL tissues were higher than
      those in mucosa of controls (P < 0.01). The expressions of Survivin in SCCL with
      the metastasis of lymph nodes were higher than those without metastasis( P <
      0.05). Age and sex did not change the expressions obviously( P > 0.05). The
      expressions of Survivin in SCCL have a positive correlation between T-stages( P <
      0.05). There was also a negative correlation in staining intensity between
      Survivin and survival time ( r = -0.646, P < 0.01). CONCLUSION: A significant
      correlation between Survivin expression and T-stage( P < 0.05), lymph node
      metastasis( P < 0.05) and prognosis (P < 0.01) was revealed in squamous cell
      carcinoma of larynx. The high expression suggests worse prognosis. The up
      regulate of Survivin suggests that it play an important role in the formation and
      metastasis of SCCL.

PMID- 15844614
TI  - [A study on primary culture in vitro of twenty-one laryngeal squamous carcinoma
      tissues].
AB  - OBJECTIVE: To study the different influent on the growth rate of laryngeal
      carcinoma cell culture in vitro between collagenase type I and trypsin and to
      provide the experiment base for laryngeal carcinoma cell culture. METHOD:
      Applying the technique of primary tissue culture in vitro, twenty-one specimens
      which were identified pathologically as laryngeal squamous cell carcinoma were
      cultured. The relation ship letwech the cell growth rate and donor age, cultured
      methods was observed. The influent factors of primary culture, such as serum of
      low concentration were analyzed. RESULT: Cell growth rate were 66% (6/9) in the
      group aged under 60.58% in the group above 60. The cell growth rate were 58% in
      collagenase type I and 13% in trypsin. Serum of low concentration can restrain
      fibroblast. CONCLUSION: The cell growth of laryngeal squamous cell carcinoma in
      vitro could be correlated with the culture methods, fibroblast outgrowth and
      microbiotic contamination are important factors in primary cell culture.

PMID- 15844615
TI  - [Expression of S-100 positive dendritic cell, TIMP-1 and p63 and its significance
      in the primary laryngeal carcinoma].
AB  - OBJECTIVE: To evaluate the predictive role of S-100 positive dendritic cell,
      tissue inhibitor of metalloproteinases-1 (TIMP-1) and p63 gene in primary
      laryngeal carcinoma with epidemiology (smoking and drinking), histological
      grading, surgical treatment, TNM stage and prognosis by the tissuechip
      technology. METHODS: We studied the expression of dendritic cell (S-100), TIMP-1
      and p63 gene on a series of 85 primary laryngeal carcinoma patients who had ever
      received in our hospital between 1992 and 2000 by the tissuechip technology and
      SP method. The correlation of each score according to the intensity and
      percentage of labeled cells or intercellular substance with relevant clinical
      dada was statistically analyzed. RESULT: Some cases were lost or boasted no tumor
      tissue in our tissuechip. In available 79 patients, the rate of expressing S-100
      positive dendritic cell is 59.5% (47/79), and the average percentage of its
      labeled cells in them is 8.71%. S-100 positive dentritic cells showed significant
      difference among different pathological grade group, early and late stage( P <
      0.05). The rate is 55.7% (44/79) of the specimens whose basal membrane and
      extracellular matrix was strongly stained by TIMP-1; There was statistical
      significant in TIMP-1 protein demonstration between early and late stages, lymph
      node metastasis and 3-year survival rate ( P < 0.05) by chi-square test, but no
      relation with smoking, drinking, gender, age and histological classes (P > 0.05).
      There was wo statistical significant in p63 protein demonstration between TNM
      stages, lymph node metastasis, 3-year survival rate, smoking, drinking, gender,
      age and histological classes (P > 0.05). CONCLUSION: The tissue microarray
      technique spent shorter time and less expense, and showed higher consistency in
      our essays. And the present study suggests TIMP-1 and S-100 could be the clinical
      discriminators in laryngeal carcinoma.

PMID- 15844616
TI  - Manipulation of zebrafish embryogenesis by phosphorodiamidate morpholino
      oligomers indicates minimal non-specific teratogenesis.
AB  - The incidence of teratogenicity caused by therapeutic agents is a significant
      concern in drug development. Approaches to screening active agents in drug
      development tend to be limited by relevance to humans, cost from the large number
      of animals required for testing and complicated by barriers to drug entry into
      the test organism. The era post-human, -mouse and -zebrafish genome sequence
      determination should result in more precise experimental approaches to the
      evaluation of teratogenic potential. Peer-reviewed publications (204 papers) from
      independent investigators evaluating phosphorodiamidate morpholino oligomers
      (PMOs) in functional genomic studies are reviewed. These studies utilized over
      47,000 embryos and resulted in 0.3% off-targeted or potential teratogenic
      effects, while at the same time producing the 74% phenotypic penetrance expected
      for the targeted gene. This represents a very compelling case for the minimal
      teratogenic potential of PMO chemistry.

PMID- 15844617
TI  - Antibacterial antisense.
AB  - The concept of using antisense antibiotics is revolutionary. Instead of targeting
      proteins or macromolecular complexes, as do traditional antibiotics, antisense
      oligomers target specific genes, rRNA or mRNA, and inhibit expression of the
      targeted sequence. Recent advances have shown that two types of antisense
      oligomer, peptide nucleic acids and phosphorodiamidate morpholino oligomers
      (PMOs), inhibit gene expression in a sequence-specific and dose-dependent manner
      at low micromolar concentrations. Cellular uptake has been improved by shortening
      the length of the antisense oligomer and/or attaching membrane-permeating
      peptides. In addition to Escherichia coli, other bacteria such as Staphylococcus
      aureus and Mycobacterium tuberculosis are susceptible to antisense antibiotics.
      The first animal studies demonstrated that PMOs reduced E. coli approximately 10
      fold in mouse peritonitis infections. Non-therapeutic uses of bacterial antisense
      are providing novel tools to identify new targets, elucidate mechanisms of
      antibiotic action and design new antibiotics. Gene-specific antisense antibiotics
      now appear possible, and additional preclinical animal studies should move this
      technology towards that goal.

PMID- 15844618
TI  - Small interfering RNA for experimental cancer therapy.
AB  - RNA interference describes the recently discovered process of sequence-specific,
      post-transcriptional gene silencing that is initiated by double-stranded RNA
      molecules known as small interfering RNAs (siRNAs). siRNAs have an acceptable
      half-life in vitro, a predictable biodistribution profile similar to that of
      single-stranded antisense oligonucleotides (ASOs), and have repeatedly been more
      robust than ASO techniques in terms of consistency of transcript knockdown and
      threshold concentration. Following validation in mammalian cells by Tuschl and co
      workers in 2001, synthetic siRNAs have gained wide acceptance as a laboratory
      tool for target validation. Currently, there is considerable interest in the
      therapeutic use of siRNA, particularly in areas of infectious disease and cancer.
      In vitro and in vivo findings demonstrate the efficacy of siRNA knockdown of gene
      messages that are pivotal for tumor cell growth, metastasis, angiogenesis and
      chemoresistance, leading to tumor growth suppression. However, siRNA-based cancer
      therapy faces similar pharmacokinetic limitations to ASO therapy with respect to
      the extent that siRNA accesses primary and metastatic target cells. The recently
      identified 'off-target activity' of siRNAs is also of concern. The concept of
      carrier-restricted delivery of siRNA by conditionally replicative, oncolytic
      adenoviruses is discussed. Oncolytic adenoviral delivery offers the potential
      benefits of restricted and renewable siRNA expression within the tumor
      microenvironment, an additive antitumor outcome through viral oncolysis and siRNA
      mediated oncogene silencing, and a proven clinical platform with respect to
      infectivity and safety.

PMID- 15844619
TI  - Transcriptional gene silencing by short interfering RNAs.
AB  - Double-stranded RNA (dsRNA)-induced sequence-specific gene silencing in animals
      and plants is known as RNA interference. In mammalian cells, although long dsRNAs
      induce an interferon-mediated, non-specific gene silencing, short interfering
      RNAs (siRNAs) that are processed from long dsRNAs by Dicer can induce sequence
      specific gene silencing. Since siRNAs can be designed for genes of interest,
      these molecules have great potential to be used as effective gene therapies. In
      plants, siRNAs targeted to CpG islands within a promoter can also induce RNA
      directed DNA methylation. In addition, siRNAs have a role in heterochromatic gene
      silencing in fission yeasts, plants and animals. Recently, siRNAs were
      demonstrated to induce transcriptional gene silencing (TGS) via DNA methylation
      in human cells. This review will focus on TGS by siRNAs, such as DNA methylation
      and histone methylation.

PMID- 15844620
TI  - Peptide-oligonucleotide conjugates for the delivery of antisense and siRNA.
AB  - Conjugation of oligonucleotides to certain types of peptides provides an
      interesting approach for enhancing delivery of antisense and siRNA to cells and
      tissues. This article will provide a perspective on issues in oligonucleotide
      delivery, and will examine recent literature on the preparation and use of
      several types of peptide-oligonucleotide conjugates.

PMID- 15844621
TI  - Allosteric aptamers and aptazymes as probes for screening approaches.
AB  - Substantial effort is currently being devoted to engineering allosteric nucleic
      acids, aptamers and ribozymes for various applications in cellular and molecular
      biology, biotechnology and diagnostics. These molecular switches alter their
      different functional activities in response to specific binding molecules,
      including proteins, nucleic acids and small organic compounds. The interacting
      molecules trigger a response in the allosteric nucleic acid, which can be used
      for purposes such as real-time monitoring, high-throughput screening or gene
      expression control.

PMID- 15844622
TI  - Heteropolymers: a novel technology against blood-borne infections.
AB  - Heteropolymer (HP) technology is a novel cassette technology which is being
      developed for the treatment of infectious and autoimmune diseases. HPs are dual
      antibody conjugates, composed of a monoclonal antibody (mAb) directed against the
      complement receptor type 1 (CR1) on primate red blood cells (RBCs) chemically
      cross-linked to mAbs that recognize blood-borne antigens. Upon administration of
      an HP, the target is bound to its counterpart mAb in the HP and immobilized on an
      RBC by binding of the anti-CR1 mAb to CR1 in a complement-independent manner,
      forming an immune complex. When the RBC traverses the liver during circulation,
      the immune complex is recognized by fixed tissue macrophages, the CR1 molecule is
      cleaved and the HP-pathogen complex is phagocytosed and destroyed. Due to rapid
      binding and immobilization of the target by HPs, the anti-target mAb used in the
      HP need not be directed to a neutralizing epitope on the target organism. Studies
      in animal models have shown that HPs are effective in treating infectious
      diseases and autoimmune diseases such as systemic lupus erythematosus. HPs are
      advantageous over natural immune adherence or conventional mAb therapies due to
      their complement-independent mechanism, low therapeutic dose and lack of the need
      for neutralizing mAbs against the target.

PMID- 15844623
TI  - Human monoclonal antibodies to the S glycoprotein and related proteins as
      potential therapeutics for SARS.
AB  - Polyclonal antibodies have a century-old history of being effective against some
      viruses and, recently, monoclonal antibodies (mAbs) have also shown some clinical
      success. Human mAbs to the severe acute respiratory syndrome (SARS) coronavirus
      spike glycoprotein have been developed by several research groups at an amazing
      pace. These antibodies potently neutralize infectious virus in tissue cultures
      and animal models, and, alone or in combination with vaccines and other drugs,
      may have potential for the prevention and treatment of SARS.

PMID- 15844624
TI  - Development of antibody-targeted vaccines.
AB  - The use of monoclonal antibodies for immunotherapy has been validated by the
      commercialization of multiple monoclonal antibody products for oncology,
      infectious diseases and autoimmune diseases. In addition to their application as
      'naked' antibodies, they have been used as delivery vehicles for cytotoxic agents
      to cancer cells. The exquisite specificity of antibodies can also be exploited to
      initiate and/or enhance the immune response to tumors or infectious agents by
      targeting the relevant antigen to antigen-presenting cells (APCs). Such antibody
      targeted vaccines (ATVs) have demonstrated remarkable activity in preclinical
      models by eliminating the need for adjuvant and repetitive boosting, overcoming
      immunological non-responsiveness, inducing mucosal immunity and eliciting
      therapeutic cytotoxic T-cell-mediated antitumor effects. A variety of different
      receptors on APCs have been exploited for targeting antigens, which may allow
      optimization for specific immune responses. Selective targeting to appropriate
      receptors on APC subsets combined with strong activating signals is important for
      generating potent cytolytic T-cell responses. Studies have also suggested that
      ATVs may be selectively exploited to induce tolerance against antigens for
      treatment against transplant rejection or autoimmune diseases. The clinical
      development of this new class of antibody-based products has recently been
      initiated.

PMID- 15844625
TI  - Technology evaluation: Rexin-G, Epeius Biotechnologies.
AB  - Rexin-G is a 'pathotropic', tumor-targeted, injectable retroviral vector carrying
      a mutant form of the cyclin G1 gene, under development by Epeius Biotechnologies
      for the potential treatment of metastatic cancer. The therapy is currently
      undergoing phase I/II clinical trials.

PMID- 15844626
TI  - Technology evaluation: cintredekin besudotox, NeoPharm/Nippon.
AB  - NeoPharm Inc, under license from the National Institutes of Health and the FDA,
      and in collaboration with the Japanese licensee Nippon Kayaku Co Ltd, is
      developing cintredekin besudotox, a chimeric human IL-13 conjugated to a
      genetically engineered Pseudomonas exotoxin molecule, as a potential antitumor
      agent. This agent is currently undergoing phase III clinical trials.

PMID- 15844627
TI  - Technology evaluation: nimotuzumab, the Center of Molecular Immunology/YM
      BioSciences/Oncoscience.
AB  - A joint venture between YM BioSciences (formerly York Medical) and The Center of
      Molecular Immunology is collaborating with Oncoscience in Europe for the
      development of a humanized monoclonal antibody, nimotuzumab, for the potential
      treatment (TheraCIM and RadioTheraCIM) and diagnosis (DiaCIM) of cancers of
      epithelial origin, such as breast, lung, head and neck, and pancreatic cancer.
      The antibody is currently undergoing phase II clinical trials.

PMID- 15844628
TI  - Quality assurance activities and the impact of the Quality of Care Information
      Protection Act, 2004.

PMID- 15844629
TI  - Demonstration of polarizable crystals in fresh comedonal extracts: sebum
      crystallizes.
AB  - Previous studies using paraffin-embedded sections showed the presence of varying
      degrees of lipidic calculus (sebolith) formation in the pilosebaceous duct in
      acne comedonal lesions. The objective of this study was to examine the content of
      fresh acne comedonal extracts and pustules in polarizable crystalline material.
      Furthermore, to investigate if the amount of crystalline material correlates with
      the morphology, evolutionary stage, age and location of the comedone we performed
      polariscopic examination of 20 fresh acne comedonal extracts and 6 acne pustules.
      As controls, we used extracts from solar comedones, milia and epidermal inclusion
      cysts, follicular extracts from acne rosacea lesions, pustules of bacterial
      folliculitis and extracts from normal follicles from acne-prone individuals. The
      vast majority of acne comedones contained considerable amounts of polarizable
      crystalline material. Crystallization was more prominent in closed comedones,
      long-standing macrocomedones and conglobate comedones. Crystal formation was seen
      less commonly (p < 0.01) in solar comedones, milia and epidermal inclusion cysts.
      As shown in this study, crystallization of sebum is a common element of
      comedogenesis and may possibly contribute to comedo preservation.

PMID- 15844630
TI  - Comparison of clinical and computerized image analyses in the assessment of skin
      ageing in smokers and non-smokers.
AB  - Tobacco smoke and UV radiation are extrinsic risk factors for accelerated skin
      ageing. In this study the effects of smoking on wrinkling and ageing were
      assessed in males living in Northern Finland, where cumulative sun exposure is
      low. Smoking habits, age and facial wrinkling were estimated from facial
      photographs of 41 smokers and 48 non-smokers by eight panellists, using a blinded
      standardized assessment. Wrinkling of 26 smokers and 31 non-smokers was also
      assessed by computerized image analysis. The panellists identified 68% of the
      smokers correctly as being smokers and the smokers were estimated as being an
      average of 2.1 years older than their age by the panellists, whereas the non
      smokers were estimated as being an average of 0.7 years younger than their age (p
      < 0.05). No significant difference in skin wrinkling was found between the groups
      by either clinical assessment or by computerized image analysis. In conclusion,
      even in the absence of increased wrinkling, the smokers looked older than their
      age and a majority of them could be identified as smokers by their facial
      features alone.

PMID- 15844631
TI  - Galanin expression in a murine model of allergic contact dermatitis.
AB  - Galanin is a neuropeptide widely distributed in the nervous system. The
      expression of galanin was investigated in murine contact allergy using
      immunohistochemistry, radioimmunoassay and in situ hybridization. Female BALB/c
      mice were sensitized with oxazolone and 6 days later challenged on the dorsal
      surface of ears, while control mice received vehicle. After 24 h, one ear was
      processed for immunostaining using a biotinylated fluorescence technique, while
      the other ear was frozen and processed for radioimmunoassay or in situ
      hybridization. Galanin immunoreactive nerve fibres were more numerous (p < 0.01)
      in the eczematous compared with control ears. Double-staining with antibody to
      the nerve fibre marker PGP (protein gene product) 9.5 revealed colocalization of
      PGP 9.5 and galanin in nerve fibres. Radioimmunoassay demonstrated a decrease (p
      < 0.04) in galanin concentration in eczematous compared with control ears. Our
      results suggest a role for galanin in murine contact allergy.

PMID- 15844632
TI  - Lysophosphatidylcholine induces keratinocyte differentiation and upregulation of
      AP-1- and NF-kappaB DNA-binding activity.
AB  - Lysophosphatidylcholine (lysoPC) is generated by the action of phospholipase A2
      on membrane phosphatidylcholine, the most abundant cellular phospholipid. In
      vitro, lysoPC has pro-inflammatory properties, as it upregulates the expression
      of adhesion molecules and is a chemoattractant to monocytes and T lymphocytes. It
      upregulates the expression of a variety of genes including genes encoding growth
      factors and cyclooxygenase-2 and modulates other cellular responses like
      proliferation and differentiation. A role for lysoPC as an intracellular
      messenger transducing signals from membrane-associated receptors has also been
      suggested. However, the mechanisms behind the diverse actions of lysoPC are
      poorly understood. In this study we found that lysoPC in non-toxic concentrations
      caused increased activator protein-1 (AP-1) DNA-binding activity and
      transglutaminase-1 expression in cultured human keratinocytes. The effects on
      transglutaminase-1 and AP-1 were dependent on protein kinase C and mitogen
      activated protein kinase kinase. In addition, lysoPC caused a rapid and transient
      increase in DNA-binding activity of nuclear factor-kappaB.

PMID- 15844633
TI  - The role of p53 codon 72 and human papilloma virus status of cutaneous squamous
      cell carcinoma in the Swedish population.
AB  - The arginine variant of the p53 codon 72 polymorphism as well as anogenital and
      epidermodysplasia verruciformis (EV) types of human papilloma virus (HPV) are
      suggested to confer increased risk for developing cutaneous squamous cell
      carcinoma (SCC). In this pilot study, we analysed the p53 codon 72 genotype
      distribution in 106 microdissected samples from normal and tumour tissues of 53
      cases of cutaneous SCC and 96 controls from Sweden. Both normal and tumour
      samples from cases of SCC were screened for anogenital and EV HPV. The p53Arg
      allele was not associated with the development of cutaneous SCC. Anogenital HPV
      (44%) was more prevalent than EV HPV (12%). Data also indicate that anogenital
      HPV is more common in tumour samples, but HPV infection was not identified as a
      significant risk factor for developing SCC. The presence of anogenital HPV, but
      not EV HPV might be a risk factor for development of cutaneous SCC.

PMID- 15844634
TI  - To follow dermatological treatment regimens--patients' and providers' views.
AB  - Adherence to long-term therapy for chronic illness is on average 50%. However,
      regarding adherence to dermatological treatment the existing literature is
      limited. The aim of the study was to acquire an understanding of issues
      associated with adherence to dermatological therapy. Focus group interviews were
      used in two types of fora: patients with chronic dermatological diseases and
      health care providers, including doctors, nurses and pharmacists working in
      dermatological care. Results reveal the providers' view of a suboptimal rate of
      adherence. According to both providers and patients, factors affecting adherence
      were patients' expectations and experiences of therapeutic effect, possibilities
      for the patient to take active part in treatment decisions, as well as mode of
      administration and type of medication. Suggested strategies for improvement are
      individualized patient education, continuous treatment support with assessment of
      medication-taking behaviour and enhanced communication skills among the
      providers.

PMID- 15844635
TI  - Paediatric skin disorders encountered in an emergency hospital facility: a
      prospective study.
AB  - To determine the frequency of skin disorders encountered in a paediatric
      emergency care unit and to evaluate the benefits of advice from a dermatologist,
      we prospectively recorded data of children admitted with skin disorders to the
      emergency care unit during a 5-month period. Diagnostic agreement between
      paediatricians and dermatologists evaluating the patients separately was
      assessed. Three hundred and ninety-five children (median age 3 years;
      interquartile 1-6) were included. Skin disorders represented 4% of all paediatric
      emergency care unit visits. Visits were considered as appropriate in 19-30% of
      cases according to different criteria. Six diseases accounted for 57% of cases:
      viral exanthema, urticaria, atopic dermatitis, varicella, diaper dermatitis and
      herpetic gingivostomatitis. The dermatologist modified the diagnosis in 42% of
      cases and the treatment in 30%. Greater emphasis on teaching the skin disorders
      encountered in this setting and efforts to provide easy access to advice from
      dermatologist would improve the quality of care.

PMID- 15844636
TI  - Sexual behaviour of male teenagers attending a City Department for Skin and
      Venereal Diseases in Belgrade.
AB  - A study of sexual behaviour of teenagers is essential in the design of an
      effective intervention programme for sexually transmitted diseases (STDs). A
      questionnaire was administered to 380 men, attending the department for skin and
      venereal diseases in Belgrade in the period from January 2000 to June 2001. Two
      groups were compared, 'STD cases' (attending for suspected STDs) and controls
      (with skin mycotic diseases). In multivariate logistic regression analysis the
      following risk factors were significantly more frequent in STD cases: sex on the
      same day as the first encounter (odds ratio (OR)= 2.62, 95% CI = 1.58-4.34),
      history of previous STD (OR = 3.60, 95% CI = 1.74-7.45) and never using a condom
      with an irregular partner (OR = 2.19, 95% CI = 1.10-4.38).

PMID- 15844637
TI  - Incidence, clinical presentation and treatment of neurosyphilis in Denmark 1980
      1997.
AB  - Neurosyphilis is now a rare disease in the developed countries. In Denmark 92
      cases of neurosyphilis were identified in the period 1980-1997. We obtained the
      hospital records for 77 of these patients and studied the clinical presentation,
      treatment and result of the treatment. Most patients were treated with penicillin
      by the intramuscular or intravenous route, but the amounts and duration of the
      antibiotic treatment varied a lot among the patients. All patients treated with
      intravenous penicillin were cured.

PMID- 15844638
TI  - Lymphomatoid papulosis associated with mycosis fungoides: clinicopathological and
      molecular studies of 12 cases.
AB  - The association of mycosis fungoides and a primary cutaneous CD30+
      lymphoproliferative disorder has been reported and probably represents different
      clinical aspects of a unique T-cell monoclonal expansion. In this study, 12
      patients (6 men and 6 women) presented with lymphomatoid papulosis and mycosis
      fungoides. A TCRgamma gene rearrangement study was performed by an automated high
      resolution PCR fragment analysis method on skin biopsy specimens taken from the
      different clinical lesions in each patient. An indolent clinical course was
      observed in the majority of patients. T-cell clonality was identified in 7 of 12
      lymphomatoid papulosis lesions (58%) and in 6 skin biopsies of plaque stage
      mycosis fungoides (50%). In each individual case, where T-cell clonality was
      detected, both mycosis fungoides and lymphomatoid papulosis specimens exhibited
      an identical peak pattern by automated high-resolution PCR fragment analysis,
      confirming a common clonal origin. Only one case showed a clonal TCRgamma
      rearrangement from the lymphomatoid papulosis lesion, which could not be
      demonstrated in the mycosis fungoides specimen. The demonstration of an identical
      clone seems to confirm that both disorders are different clinical manifestations
      of a unique T-cell monoclonal proliferation. Our results also seem to confirm
      that the association of mycosis fungoides with a primary cutaneous CD30+
      lymphoproliferative disorder usually carries a favourable prognosis.

PMID- 15844639
TI  - Panniculitis due to non-tuberculous mycobacteria in two immunocompromised
      patients.
AB  - Inflammation of subcutaneous tissue (panniculitis) may occur in association with
      tuberculosis, but so far only three cases of non-tuberculous mycobacteria-related
      lobular panniculitis have been reported. We describe two new cases with marked
      cellular immunity failure due to hypercorticism. Clinical presentation did not
      differ significantly from lobular panniculitis of other aetiologies. Histological
      samples displayed signs of lobular panniculitis and clues for mycobacteria
      infection with granulomatous lesions and presence of numerous acid-fast bacilli
      on special staining. Both patients responded quickly to a combination of
      macrolides, ethambutol and fluoroquinolones. However, like in other infections
      with tuberculous or non-tuberculous mycobacteria, long-term treatment (at least 6
      months) was necessary to prevent relapses.

PMID- 15844640
TI  - Terbinafine-induced subacute cutaneous lupus erythematosus.
AB  - Oral terbinafine is licensed for use in onychomycosis after positive confirmation
      of infection. We describe five cases of subacute cutaneous lupus erythematosus
      associated with terbinafine therapy. All cases had positive antibodies to
      extractable nuclear antigens, predominantly anti-Ro, and several had a history of
      pre-existing autoimmune disease. Terbinafine should only be prescribed after
      confirmation of infection by microscopy or culture.

PMID- 15844641
TI  - Basal cell carcinomas in port-wine stains treated with thorium X.

PMID- 15844642
TI  - Subungual hyperkeratosis of the big toe due to Bipolaris hawaiiensis.

PMID- 15844643
TI  - Successful treatment of multicentric reticulohistiocytosis with a combination of
      infliximab, prednisolone and methotrexate.

PMID- 15844644
TI  - Vegetating iododerma and pulmonary eosinophilic infiltration. A simple co
      occurrence?

PMID- 15844645
TI  - Mirtazapine for chronic urticaria.

PMID- 15844646
TI  - Solitary premature sebaceous hyperplasia associated with acneiform eruption.

PMID- 15844647
TI  - Sequential reactivation of herpesvirus in drug-induced hypersensitivity syndrome.

PMID- 15844648
TI  - Granuloma faciale associated with sinonasal tract eosinophilic angiocentric
      fibrosis.

PMID- 15844649
TI  - Female androgenetic alopecia treated by finasteride: a case forward.

PMID- 15844650
TI  - Acquired perforating primary osteoma cutis.

PMID- 15844651
TI  - Dramatic efficacy of oral aromatic retinoid in long-standing hypertrophic lupus
      erythematosus.

PMID- 15844652
TI  - Two cases of alopecia areata associated with Takayasu arteritis.

PMID- 15844653
TI  - Photolocalized varicella.

PMID- 15844654
TI  - Multiple halo naevi associated with carcinoid in a young man.

PMID- 15844655
TI  - Anaphylaxis after dental treatment with a formaldehyde-containing tooth-filling
      material.

PMID- 15844656
TI  - Body dysmorphic disorder of twins with facial illness after successful
      isotretinoin therapy.

PMID- 15844658
TI  - Inhibition of TF gene expression by antisense oligonucleotides in different
      cancer cell lines.
AB  - Human tissue factor (TF) is the initiator of blood coagulation. Beside this
      function it is involved in tumor angiogenesis and metastasis. In the study we
      have evaluated the efficiency of antisense oligonucleotides (AS-ODNs) against TF
      selected from computational prediction of TF mRNA structure. Fourteen different
      AS-ODNs were tested in three cell lines of different origin with a high TF
      content. In cell line MCF-7 expression of TF gene was inhibited up to 50% by the
      AS-ODN AS-7 in comparison to reference. To investigate the dependence of
      inhibition efficiency on the AS-ODN position inside a potential target motive we
      designed further AS-ODNs shifted 2-3 nt among AS-7. One AS-ODN was found as more
      effective than AS-7. In cell line T508 were obtained moderate effects in
      inhibition of TF gene expression of 30% by AS-4. In J82 cells TF protein was
      inhibited up to 68% by two AS-ODNs. In conclusion, we compared inhibition of TF
      gene expression in different cancer cell lines and found that all effective AS
      ODNs were located in the translated region of TF mRNA. Suitability of a target
      region of an AS-ODN is relatively independent on cell line. In contrast, optimal
      transfection conditions are dependent on cell line.

PMID- 15844657
TI  - Atiprimod is an inhibitor of cancer cell proliferation and angiogenesis.
AB  - Atiprimod, a novel compound belonging to the azaspirane class of cationic
      amphiphilic drugs, exhibits both anti-proliferative and anti-angiogenic
      activities. Atiprimod inhibited proliferation of all human cancer cell lines
      included in the National Cancer Institute panel with IC50 values in the low
      micromolar range. Notably, metastatic cell lines were more sensitive to the
      compound compared to the non-metastatic cell lines derived from the same tumor
      tissue types. Atiprimod also induced apoptosis and activated both caspase-9 and
      caspase-3 in T84 colon carcinoma cells. Hence, the anti-proliferative activity
      could partly be due to its pro-apoptotic activity. Regarding angiogenesis in
      vitro, atiprimod inhibited both bFGF and VEGF induced proliferation and migration
      of human umbilical vein endothelial cells (HUVECs), resulting in disruption of
      cord formation. In addition, atiprimod also suppressed formation of new blood
      vessels in a chorioallantoic membrane assay. Previous studies have also shown
      that atiprimod treatment reduced production of IL-6, VEGF and inhibited
      activation of Stat3, a constitutively activated protein in majority of human
      cancers. Together these findings suggest that atiprimod acts on several molecules
      that are essential for tumor growth, invasion and metastasis.

PMID- 15844659
TI  - The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in
      prostate cancer metastasis.
AB  - AIM: Chemokines or chemotactic cytokines are known to be important in the
      directional migration or chemotaxis of leucocytes in conditions of homeostasis
      and in inflammatory or immunological responses. However, the role of chemokines
      is extending beyond their involvement in mediating leucocyte trafficking with an
      increasing body of evidence suggesting these proteins are intimately involved in
      many stages of tumour development and progression. Our aim was to study the role
      of the CXCL12:CXCR4 chemokine ligand:receptor complex in determining the organ
      specific metastasis of prostate cancer. MATERIALS AND METHODS: CXCR4 mRNA
      expression was determined by RT-PCR in 3 metastatic prostate cancer cell lines
      DU145, LNCaP and PC3, the primary prostate cancer cell line 1542 CPT3X and the
      normal prostate epithelial cell lines 1542 NPTX and Pre 2.8. This was followed by
      Taqman quantitative PCR analysis of CXCR4 mRNA in these cell lines. Flow
      cytometry analysis was then used to measure the expression of the CXCR4 receptor
      protein on the cell surface. The influence of the receptor on cell migration was
      studied using Transwell, Migration Assays. Finally, Taqman quantitative PCR was
      performed on RNA obtained from laser microdissected fresh primary prostate tumour
      and benign tissue samples from patients. RESULTS: In DU145, LNCaP and PC3 CXCR4
      mRNA expression was approximately 1000, 400 and 21 times respectively that of
      1542 NPTX, Pre 2.8 and 1542 CPT3X. In patient primary tumour samples and patient
      benign tissue specimens CXCR4 mRNA expression was similar to that of the
      metastatic cell line DU145. Flow cytometry analysis showed that significantly
      higher levels of the CXCR4 receptor were present on the cell surface of the 3
      metastatic cell lines. Migration studies revealed that chemotaxis of the
      metastatic cell lines PC3 and DU145 was enhanced by CXCL12 ligand and inhibited
      by antibody to CXCR4. CXCL12 did not influence the migration of the normal
      prostate epithelial cell line 1542 NPTX. CONCLUSIONS: We have demonstrated that
      human prostate cell lines derived from metastases express functional CXCR4
      receptor and that CXCL12 ligand enhances their migratory capabilities. Also,
      laser microdissected primary patient tumours and patient benign tissue specimens
      express CXCR4 mRNA at high levels (it is suggested that post-transcriptional
      modification of the CXCR4 receptor plays a major role in regulating protein
      expression). These results suggest prostate cancers may be influenced by the
      CXCL12:CXCR4 pathway during metastasis. This pathway would provide a novel target
      for therapeutic intervention.

PMID- 15844660
TI  - Radioimmunotherapy in non-Hodgkin's lymphoma: focus on 90Y-ibritumomab tiuxetan
      (Zevalin).
AB  - Radioimmunotherapy (RIT), in which a radionuclide conjugated to an antibody
      directed towards a tumor associated antigen (the radioimmunoconjugate) is
      administered in a therapeutic regimen, represents a significant addition to the
      treatment of non-Hodgkin's lymphoma (NHL). RIT offers several advantages for this
      heterogenous disease, foremost being the ability to kill tumor cells adjacent to
      cells to which the radioimmunoconjugate is bound (the cross-fire effect). Thus,
      RIT is cytotoxic to tumor cells that may be inaccessible to the antibody, or do
      not express the target antigen in sufficient quantities for antibody binding. The
      radioimmunoconjugate 90Y-ibritumomab tiuxetan is directed against the B-cell
      antigen, CD20. Phase II and III clinical trials with this agent report overall
      response rates of 74% to 83% (complete response rates 15% to 51%) in patients
      with relapsed or refractory, indolent or transformed NHL, including patients
      refractory to rituximab. Median durations of response range up to 13.9 months. A
      variety of RIT approaches are under investigation to improve outcomes in patients
      with NHL, including the use of radioimmunoconjugates combined with chemotherapy,
      and myeloablative therapeutic strategies.

PMID- 15844662
TI  - Serum protein profiling of lung cancer patients.
AB  - Lung cancer is one of the leading causes of cancer deaths worldwide. The poor
      patients prognosis is largely attributable to the lack of effective early
      detection methods. Based on the concept that proteins and peptides can emanate
      from tumor to the serum, the present study aims to investigate if serum proteins
      pattern, assessed by a gradient polyacrylamide gel, is capable to discriminate 66
      lung cancer patients from 44 healthy donors. Additionally, in a group of 10
      patients and 10 healthy donors, it was also investigated by western-blot if
      apoptosis and metastasis-related proteins such as Bax, Bcl-2 and Hlm were present
      in serum. Our results showed that, in patients, protein bands of 180 kDa and 13
      kDa were more frequent (Fisher, P<0.05) and a protein band of 124 kDa was more
      intense (Mann Whitney, P<0.05). In healthy donors a band of 158 kDa were more
      frequent (Fisher, P<0.05), a band of 24 kDa was more intense (Mann Whitney,
      P<0.05) and bands of 14 kDa and 9 kDa were together more frequent (Fisher,
      P<0.05) and intense (Mann Whitney, P<0.05). Bax, Bcl-2 and Hlm were not detected
      in serum. We conclude that changes in serum protein pattern of lung cancer
      patients can be detected by a simple methodology.

PMID- 15844661
TI  - Cyclooxygenase-2 induction and prostaglandin E2 accumulation in squamous cell
      carcinoma as a consequence of epidermal growth factor receptor activation by
      imatinib mesylate.
AB  - Imatinib mesylate is a novel anti-tumor agent useful in the clinical management
      of chronic myelogenous leukemia and gastrointestinal stromal tumors with minimal
      toxicity relative to other forms of cancer therapy. Its clinical activity and
      minimal toxicity are related to specific inhibition of cellular targets including
      BCR-ABL, platelet-derived growth factor receptor and c-kit kinases, resulting in
      the collapse of downstream signaling cascades important for transformation. In
      some patients, unexpected toxicities arise that are not associated with
      inhibition of any known cellular imatinib target. In this report, we investigated
      the effects of imatinib on squamous carcinoma cell signaling. Imatinib induced
      expression of COX-2 in a dose-dependent manner with concomitant accumulation of
      prostaglandin E2. COX-2 induction by imatinib was initiated through epidermal
      growth factor (EGF) receptor kinase activation and downstream signaling through
      mitogenic-activated protein kinase. COX-2 induction by imatinib was blocked by
      MEK1 or EGF receptor inhibition. Imatinib did not activate stressor cytokine
      signaling pathways (p38 kinase, nuclear factor-kB nuclear translocation) or
      affect COX-1 expression. Imatinib failed to activate EGF receptor signals in
      other tumor types, suggesting that COX-2 induction in imatinib-treated cells is
      mediated through release of autocrine factors expressed or activated in squamous
      tumors. COX-2 induction by imatinib in squamous tumors derived from the head and
      neck region is unique with respect to other target-specific agents and may
      represent one of the unintended toxic effects of imatinib described in some
      patients.

PMID- 15844663
TI  - Effect of arsenic trioxide (ATO) on human lung carcinoma PG cell line: ATO
      induced apoptosis of PG cells and decreased expression of Bcl-2, Pgp.
AB  - Arsenic trioxide (ATO) has been established to be an effective agent for treating
      newly diagnosed and relapsed acute promyelocytic leukemia (APL) patients.
      Laboratory data suggest that ATO induces apoptosis of hematopoietic or several
      solid tumor cells. However, to date, its effect on lung carcinoma has not been
      fully explored. In the present study, we investigated the effect of ATO on human
      lung carcinoma PG cells in vitro. We found ATO significantly inhibited the
      proliferation of PG cells in a dose- and time-dependent manner. ATO-induced
      apoptosis of PG cells was confirmed by the observance of typical morphological
      changes and detected by the analysis of flow cytometry (FCM). ATO significantly
      inhibited Bcl-2 and Pgp expression of PG cells by SABC immunohistochemistry and
      FCM analysis. In conclusion, our findings indicated that ATO induced apoptosis of
      PG cells and down-regulation of Bcl-2 and Pgp expressions, and these data might
      provide some theoretical basis for its clinical use in treating lung carcinoma.

PMID- 15844664
TI  - Phase II study of nedaplatin and irinotecan for elderly patients with advanced
      non-small cell lung cancer.
AB  - We conducted a phase II study of combination chemotherapy with nedaplatin (NP)
      with irinotecan (CPT) to determine the effects against unresectable non-small
      cell lung cancer (NSCLC) and to determine the qualitative and quantitative
      toxicities of this combination chemotherapy in 70 years or older patients. Thirty
      eight patients received 100 mg/m2 NP on day 1 and 60 mg/m2 CPT on days 1 and 8
      every four weeks. Twenty-five patients achieved PR, nine SD and three PD, and the
      overall response rate was 65.8%. Nineteen patients (50%) experienced grade 4
      neutropenia. Neutropenic fever occurred in 11 patients (29%) and one of them
      died. Of other grade 3 non-hematologic toxicities, two patients experienced
      diarrhea; one interstitial pneumonitis; one liver injury; and one rash. The
      median survival time was 418 days and the one-year survival rate was 55.3%. In
      conclusion, NP combined with CPT is an active treatment for elderly patients with
      NSCLC.

PMID- 15844665
TI  - Relaxation as a cognitive task.
AB  - In the present experiment the instruction to relax was given to awake highly
      (Highs) and non hypnotizable subjects (Lows), while their heart rate, respirogram
      and skin resistance were recorded together with electroencephalogram,
      electroculogram and corrugator electromiogram. At the beginning of the
      experiment, Highs exhibited no significant difference in heart rate (HR),
      respiratory frequency (RF) and heart rate variability (HRV) with respect to Lows,
      but showed a higher EEG alpha and theta1 power. During the session, both groups
      decreased their heart rate, but changes were significant only in Lows, which
      increased significantly also the parasympathetic component of their HRV (high
      frequency, HF). In both groups, EEG showed alpha, beta2 and theta2 power
      decrements; theta1 activity decreased only in Lows, while gamma power increased
      in Highs and decreased in Lows. Results suggest that Highs and Lows used
      different cognitive strategies in the elaboration of the relaxation request and
      that Highs performed the task through a higher integrative activity.

PMID- 15844666
TI  - Effects of 5-hydroxytryptamine on the neuronal firing rate of bulbar reticular
      neurons.
AB  - The effects of 5-hydroxytryptamine (5-HT) on neuronal firing rate were studied in
      the reticular gigantocellular nucleus (GRN) and, for a comparison, in the
      interstitial (IRN), the parvicellular (PRN) and the lateral (LRN) nuclei, sharing
      some of GRN functional characteristics. Unitary extracellular recordings
      performed in anesthetized rats demonstrated that microiontophoretic application
      of 5-HT modulated the background firing rate in 92% of GRN, in 100% of IRN and
      LRN, and in 77% of PRN tested neurons. In GRN, 5-HT application induced
      excitatory responses in 49% of the neurons tested and inhibitions in 43% of them.
      Both types of effects were dose dependent and appeared scattered throughout the
      nucleus. Enhancements and decreases of firing rate in response to 5-HT
      application were also recorded in IRN (58% and 42% respectively), LRN (43% and
      57%) and PRN (36% and 41%). The 5-HT(1A) receptor agonist 8-hydroxy-2(di-n
      propylamino)tetralin (8-OH-DPAT) mimicked 5-HT evoked inhibitions in all the
      nuclei tested and induced weak inhibitory responses also in neurons excited by 5
      HT. The 5-HT2A receptor agonist alphamethyl-5-hydroxytryptamine (alpha-me-5-HT)
      mimicked excitatory as well as inhibitory responses to 5-HT, the former
      prevailing in GRN and the latter in the remaining reticular nuclei. Both
      excitatory and inhibitory responses to 5-HT were partially or totally blocked by
      the application of 5-HT2 receptor antagonist ketanserin. It is concluded that an
      extended, strong and differentiated control is exerted by 5-HT on the electrical
      activity of bulbar reticular neurons. Both 5-HT(1A) and 5-HT(2A) receptors
      mediate these effects, but the involvement of other receptors appears probable.

PMID- 15844667
TI  - Mapping of tachykinins in the cat spinal cord.
AB  - Using an indirect immunoperoxidase technique, the location of cell bodies and
      fibers containing substance P, neurokinin A and neurokinin B was studied in the
      cat spinal cord. The former two neuropeptides showed a widespread distribution
      throughout the whole spinal cord, whereas the distribution of neurokinin B was
      more restricted. Neurokinin A-immunoreactive structures showed a more widespread
      distribution and a higher density than the immunoreactive structures observed to
      contain substance P. In the cat spinal cord, we observed cell bodies containing
      neurokinin A, but no cell bodies containing neurokinin B or substance P were
      found. These cell bodies were located in laminae V (sacral 1 and 2 levels), VI
      (sacral 1 and 3), VII (lumbar 7, sacral 1 and 3, caudal 1) and X (sacral 1).
      Laminae I and II showed the highest density of immunoreactive fibers for each of
      the three tachykinins studied, being in general lamina IV who showed the lowest
      number of immunoreactive fibers containing substance P, neurokinin A or B. The
      anatomical distribution of the three tachykinins studied in the cat spinal cord
      indicates that the neuropeptides could be involved in the neurotransmission
      and/or in the neuromodulation of nociceptive information, as well as in autonomic
      and affective responses to pain. Moreover, the involvement of substance P,
      neurokinin A or B in other functions unrelated to the transmission of pain is
      also possible (autonomic and motor functions). The distribution of the
      neuropeptides studied in the cat is compared with the location of the same
      neuropeptides in the spinal cord of other species. The possible origin of the
      tachykinergic fibers in the cat spinal cord is also discussed.

PMID- 15844668
TI  - Analysis of the unfused tetanus course in fast motor units of the rat medial
      gastrocnemius muscle.
AB  - The course of unfused tetani with the sag effect in fast motor units of rat
      medial gastrocnemius was studied. The analysis of the course of successive
      contractions within these tetani showed that the high peak force at the beginning
      of tetanus before the sag resulted from temporary, very efficient sum mation of
      contractions at this phase, both in FF (fast fatigable) and FR (fast resistant to
      fatigue) units. The process of summation developed in spite of parallel
      shortening of the contraction and relaxation. The peak of tetanus force was
      visible on the average at the 2nd contraction in FF units and at the 5th
      contraction in FR units. After the tetanus peak the process of the efficient
      summation was completed and the force decreased what was visible as a sag. In the
      following part of the tetanus, mainly in FF units, the potentiation occurred and
      the force of successive contractions increased. The rise of force was visible in
      spite of shortening of the contraction time and was due to prolongation of the
      relaxation in this part of the tetanus. These observations indicated that the
      processes of the summation of successive contractions before sag and during the
      potentiation underwent different mechanisms discussed in this paper. Considerable
      release of Ca2+ ions from the sarcoplasmic reticulum was proposed as a possible
      mechanism responsible for a very efficient summation at the beginning of the
      tetanus whereas phosphorylation of regulatory light chain of myosin (RLC) in
      muscle fibers was considered as the reason of potentiation. Moreover, the present
      analysis revealed that previously found differences in tetani profiles between FF
      and FR units resulted from faster development of described changes in the course
      of contractions summating into the tetanus in FF motor units.

PMID- 15844669
TI  - Slow wave and rem sleep mechanisms are differently altered in hereditary pick
      disease associated with the TAU G389R mutation.
AB  - Sleep disturbances are found in the course of most dementing syndromes. We report
      a longitudinal polysomnographic and 18FDG-PET study in a 38-year-old male with
      FTDP17 carrying the Tau gene mutation G389R. All-night sleep EEG and wake
      cerebral glucose metabolism at rest (eyes/ears covered) of the preceding day were
      studied twice, eight months (Night 1; PET 1) and sixteen months (Night 2; PET 2)
      after the initial neurological evaluation. The Night 1 study showed sleep
      fragmentation associated to a short REM latency and a severe reduction of slow
      wave sleep, with relatively preserved NREM-REM sleep cycles; daytime PET 1
      revealed severe cerebral glucose metabolic reductions in frontal and temporal
      areas, with relative preservation of remaining cortical regions and subcortical
      structures. On Night 2, the total sleep time was less than 5 hours, delta sleep
      and REM latency remained shortened and only two sleep cycles could be identified;
      daytime PET 2 exam revealed a greater cortical metabolic impairment and an
      involvement of subcortical brain regions as compared to PET 1. Post-mortem
      neuropathological data showed severe neuronal loss, spongiosis and gliosis that
      were mostly marked in cortical layers I, II, V and VI. In vivo, neurometabolic
      and post-mortem neuropathological data are consistent with and indicative of a
      severe dysfunction of intra- and trans-hemispheric regional connectivity and of
      cortico-thalamic circuits. These findings suggest that the decreased cortical and
      subcortical connectivity may have been the main pathophysiological mechanism
      responsible for delta sleep reduction and the cognitive decline.

PMID- 15844670
TI  - Workstyle: development of a measure of response to work in those with upper
      extremity pain.
AB  - Workstyle or the behavioral, cognitive, and physiological response that can occur
      in some individuals to increases in work demands has been proposed to help
      explain the link between ergonomic and psychosocial factors in the exacerbation
      of work-related upper extremity symptoms. Currently, there is no measure of this
      construct, hindering research on its potential link to work related upper
      extremity problems in the workplace. The present study describes the development
      and psychometric properties of a measure of workstyle. Questionnaire items
      reflecting dimensions of workstyle as per the original conceptualization were
      generated primarily through focus groups with office workers and separate groups
      held with occupational physicians, physical therapists, occupational health
      psychologists, and experts in ergonomics, behavioral science, and human factors.
      Items created through this process were then administered to 282 symptomatic and
      asymptomatic office workers. Measures of job stress, ergonomic risk, upper
      extremity symptoms, and functional limitations were also obtained. The workstyle
      questionnaire was divided into two broad dimensions: Characteristic responses to
      work and Response to increased work demands. The scale development process as
      indicated by factor analysis yielded subscales that are theoretically consistent
      with the workstyle construct. These subscales include: working through pain,
      social reactivity at work, limited workplace support, deadlines/pressure, self
      imposed work pace/workload, breaks, mood, pain/tension, autonomic response, and
      numbness tingling. The internal consistency of these subscales varied from 0.61
      to 0.91, n = 282 while the test-retest (3 weeks) reliability for the various
      subscales ranged from r = 0.68 to 0.89, n = 143. A total workstyle score was
      computed that excluded the pain/tension and numbness/tingling subscales to avoid
      circular reasoning in terms of the measure's relationship to outcomes of pain and
      functional limitations. The total score was stable over time and provided unique
      variance in relation to traditional measures of job stress. Total workstyle score
      was significantly associated with higher levels of pain, and greater functional
      limitations. Dimensions of the workstyle construct were identified. The workstyle
      measure possesses acceptable psychometric properties in office workers who work
      with computers. This measure can be used in future studies on the interaction of
      psychosocial and ergonomic factors in the exacerbation of upper extremity pain
      and functional limitation.

PMID- 15844671
TI  - Back strength and flexibility of EMS providers in practicing prehospital
      providers.
AB  - In the execution of prehospital care duties, an EMS provider may be required to
      carry equipment and patients over long distances or over multiple flights of
      stairs at any time of the day. At a minimum, a prehospital provider must have
      sufficient lower back strength and hamstring flexibility to prevent
      musculoskeletal injury while lifting. This study administered fitness assessments
      related to the occupational activities of the prehospital provider with the
      purpose of describing the incidence of occupational back injury and percentage of
      providers with known risk factors for back injury. Ninety subjects were tested
      during a regional EMS conference. Men were significantly taller and heavier than
      women and had significantly less hamstring flexibility. Body Mass Index was 30.7
      +/- 7.2 in men and 28 +/- 5.7 in women. However, no significant differences were
      noted in an extension test of back strength. When surveyed, 47.8% of subjects
      reported a back injury in the previous 6 months but only 39.1% of these injuries
      were sustained while performing EMS duties. While only 13% of these injuries
      resulted in missed work, 52.2% reported their injury interfered with their daily
      activities. In spite of the physical nature of the profession, EMS providers in
      our sample were significantly overweight according to their Body Mass Index and
      may lack sufficient back strength and flexibilityfor safe execution of their
      duties. This group of professionals may be at risk for occupational injury and
      should be targeted for interventions to improve strength and flexibility.

PMID- 15844672
TI  - Self-report measure of low back-related biomechanical exposures: clinical
      validation.
AB  - Low back pain and symptoms are major contributors to ambulatory visits, economic
      burden, and reduced readiness among military personnel and employers in the
      civilian workplace as well. While a link between low back pain and biomechanical
      exposures has been established, efficient surveillance methods of such exposures
      are still needed. Furthermore, the utility of self-report measures for
      biomechanical exposures has not been examined extensively. The present cross
      sectional study analyzed questionnaire data from US Army soldiers (n = 279)
      working in previously identified occupational specialties that were associated
      with high risk for low back pain and/or low back pain disability. Demographic
      characteristics, physical workload, health behaviors, and psychosocial factors
      were assessed in addition to self-reported workplace biomechanical exposures
      using the Job Related Physical Demands (JRPDs). Outcomes included self-reported
      low back pain severity, low back symptoms, functional limitations, and general
      physical health. The results indicated that the self-report measure of
      biomechanical exposure had a high degree of internal consistency (Cronbach alpha,
      0.95). The JRPD index correlated with low back symptoms, pain intensity,
      function, and perceived work load using the Borg scale. Regression analyses
      indicated statistically significant associations between the JRPD and back pain
      specific pain severity and physical function, but not for general physical health
      (SF-12) after controlling for age, gender, educational level, job type, and
      reported exercise and work stress. Specifically, higher JRPD scores (representing
      greater biomechanical exposure) were associated with higher levels of pain
      intensity and functional limitations. Higher JRPD scores were found to place an
      individual at a greater likelihood for being a case with low back pain within the
      past 12 months (OR = 1.01 per point increase in scale-95%; range 38-152; CI =
      1.00-1.02, p < or = 0.05). While future longitudinal studies of the JRPD
      determining the predictive validity of the measure are needed, the present study
      provides evidence of the utility of the JRPD for assessing biomechanical
      exposures associated with low back pain within high-risk jobs. The findings
      suggest that the JRPD may assist with surveillance efforts and be useful as a
      process and/or outcome measure in research related to occupational
      rehabilitation.

PMID- 15844673
TI  - Review of epidemiologic studies on occupational factors and lower extremity
      musculoskeletal and vascular disorders and symptoms.
AB  - The epidemiologic literature on lower extremity musculoskeletal disorders (MSDs),
      vascular disorders, and occupational mechanical factors is relatively sparse,
      compared to the low back and upper extremities. The present literature review
      aims to summarize and evaluate the current literature on lower extremity vascular
      disorders, MSDs, and symptoms, and to update previous literature reviews. A
      search was conducted in PubMed. Articles were included if they had a lower
      extremity musculoskeletal outcome, and a workplace factor(s). They were evaluated
      based upon their generalizability, exposure, and outcome assessments, study
      design, and controlling of confounders. Most of the literature has focused on
      osteoarthritis of the hip and knee, whereas not much research has been done
      examining the feet/ankles and lower legs. Overall, better exposure assessment is
      needed to examine the causal pathway between occupational factors and MSDs.

PMID- 15844674
TI  - Employer, insurance, and health system response to long-term sick leave in the
      public sector: policy implications.
AB  - This study has been conducted to describe the situation of long-term sick-listed
      persons employed in the public sector regarding the medical reasons of their sick
      leave, the duration of their problems, the duration of the actual sick leave,
      rehabilitation support, rehabilitation measures, and the persons expectations of
      the future. Response rate of a postal questionnaire, where 484 women and 51 men
      on long-term sick leave answered, was 69%. The study-group consisted of 90% women
      with a median age of 50 years. The most common reasons for sick listing were long
      lasting musculoskeletal problems, especially neck/shoulder pain, low back pain
      and osteoarthritis or other joint problems and mental problems, especially
      depression and burn-out syndromes. Forty-seven procent of the men and 57% of the
      women had been on the sick list for more than a year. Only half of them had been
      subjected to the legally required rehabilitation investigation of the employer
      This half got access to rehabilitation programs and/or vocational rehabilitation
      to a greater extent than those who not had been subjected to rehabilitation
      investigation. Less than half had been in contact with the workplace-connected
      rehabilitation actors, the Occupational Health Service or the Trade Union. In
      spite of this the sick-listed persons had a positive view of their future return
      to work. For long-term sick-listed persons in the public sector, there is a great
      potential for improvements of the rehabilitation at the workplace arena, in the
      involvement and cooperation between the already existing rehabilitation actors,
      in order to promote return to work.

PMID- 15844675
TI  - Cognitive-behavioral group therapy as an early intervention for insomnia: a
      randomized controlled trial.
AB  - A randomized controlled design was used with a 1-yr follow-up. The purpose was to
      compare the effects of two early interventions, a cognitive-behavioral group
      intervention and a self-help information package, in patients with insomnia. In
      sum, 165 individuals seeking care for insomnia of 3-12 months duration were
      randomized to either a group receiving a CBT intervention or a group receiving a
      self-help information package. At the 1-yr follow-up, 136 participants had
      completed the entire study. At the 1-yr follow-up, the CBT group intervention
      was, compared with the control group, effective in producing reductions in
      dysfunctional beliefs and attitudes about sleep, negative daytime symptoms, as
      well as vital improvements in sleep (i.e. sleep onset latency, time awake after
      sleep onset, total sleep time, sleep quality, and sleep efficiency). In
      comparison with the control group, significantly more participants in the CBT
      group met criteria at the 1-yr follow-up for clinically meaningful improvements
      in sleep onset latency, time awake after sleep onset, and sleep efficiency. A CBT
      group intervention may well be a viable early intervention for patients with
      insomnia in a wide range of health services.

PMID- 15844676
TI  - Are gender, marital status or parenthood risk factors for outcome of treatment
      for chronic disabling spinal disorders?
AB  - Recent clinical research has suggested that single working mothers may differ in
      their response to health treatment and outcomes, relative to their married female
      or male counterparts. The present study explored, on an a priori basis, the
      existence and extent of differences in chronic pain rehabilitation outcomes of
      pain report, return-to-work and future health utilization for single working
      mothers, relative to other patients. A cohort of 1,679 consecutive chronically
      disabled work related spinal disorder (CDWRSD) patients were placed into one of
      eight groups as a function of gender, marital status (single/married), and
      parenthood (with/without children). All patients completed an assessment battery
      measuring psychosocial variables at pre- and post-treatment, and a structured
      clinical interview evaluating socioeconomic outcomes at 1 year following
      completion of a 5-7 week functional restoration program. Results revealed that
      single females with children differed from all other groups in racial
      representation, with 57.1% of these individuals being African American, widely
      disparate from the prevailing local ethnicity. Single females and males with
      children were represented by a higher incidence of cervical injuries (25.0% and
      26.7%, respectively) than all other groups (5.4-16.6%, p < .001). Contrary to
      expectation, the 8 groups did not differ significantly in program completion
      rate, work return, work retention, health utilization, recurrent injury or case
      settlement rates at one-year follow-up. The single females with children group
      did display greater levels of depression pre-treatment compared to the other
      groups. However, at post-treatment, these differences no longer existed. This
      investigation is one of the first to examine if the combination of gender and
      parenthood distinguishes significantly among CDWRSD patients. Overall, contrary
      to expectation, the single mothers did not show any significant differences in
      CDWRSD outcome at one-year post-rehab follow-up, and the single mothers and
      fathers showed no differences in depression or pain severity post-treatment.
      Thus, in spite of the societal belief to the contrary, it seems that single
      parent patients can show similar chronic pain rehabilitation outcomes, relative
      to other CDWRSD patients, after a prescribed course of tertiary functional
      restoration rehabilitation.

PMID- 15844677
TI  - Reliability and validity of a new computer-administered pictorial activity and
      task sort.
AB  - Development of a new pictorial activity and task sort and examination of its
      reliability and validity is described. The Multidimensional Task Ability Profile
      (MTAP) is the latest in a series of measures that use a combination of drawings
      and task descriptions in a self-report format to assess functional capacity. The
      MTAP is found to be reliable on a test-retest and split-half basis. The
      concurrent validity of the MTAP was examined in performance testing of lift
      capacity. Results demonstrate that the MTAP has good concurrent validity.

PMID- 15844678
TI  - Psychosocial factors related to lower back problems in a South African manganese
      industry.
AB  - The purpose of this study was to determine the association between the prevalence
      of lower back problems, fear-avoidance beliefs, and pain-coping strategies in
      using an analytical cross-sectional epidemiological study among a group of 109
      workers in a South African manganese industry. Outcome (LBP) was defined using a
      guided questionnaire and functional rating indexes. Exposure to psychosocial risk
      was determined using the Fear-Avoidance Beliefs (FABQ) and Coping Strategies
      (CSQ) questionnaires. Using inclusive and stringent definitions for perceived
      LBP, point prevalence was 37.6 and 29.4%, respectively. Only 8 cases of LBP were,
      however; recorded officially over a 7-year period reflecting a tendency of
      underreporting. Multivariate logistic regression analyses indicated significant
      adjusted relative risk ratios (RR) for work-related fear-avoidance beliefs (RR
      2.35; 95% CI 1.39-3.95) as a singular psychosocial risk while no specific coping
      strategy could be isolated. In conclusion, work hardening and a contented ethos
      of the manual laborers under study moderates the association between the
      prevalence and etiology of LBP.

PMID- 15844679
TI  - Individual factors and GP approach as predictors for the outcome of
      rehabilitation among long-term sick listed cases.
AB  - There appears to be a lack of evidence concerning the effect of rehabilitation
      programmes for the long-term sick. More focus in this area would supplement an
      approach that has been directed toward process evaluation of rehabilitation
      programmes. It was the purpose of this study to shed light on individual factors
      and health care and social welfare-related factors, which play a role for the
      outcome of rehabilitation programmes. In connection with a participatory, action
      oriented outpatient rehabilitation program, a questionnaire survey was performed
      among the programmes participants ("clients"). Questionnaires were completed
      before the rehabilitation programme's start, at the end of the 8-week programme,
      and at the 9-months follow-up. Among 389 clients, 271 (69.7%) participated in the
      study at baseline as well at the 9-months follow-up. The majority of 212
      participants were on sick leave--6.6% for more than 1 year. The remainder had
      been transferred to receiving social benefits after having exceeded the time
      limit for being sick-listed. A plan of action for active rehabilitation, which
      was made at the end of the 8-week rehabilitation programme, was only poorly
      fulfilled after 9 months, 48% were still on sick leave or social benefits at this
      time. Individual background variables, as well as psychological well-being,
      mental health, pain level, and pain coping, seemed to have little effect on the
      outcome of rehabilitation, whilst clients' own evaluations of competence and
      ability of the involved health care professionals were found important for a
      positive outcome of the programme. Especially stable relations to a single
      General Practitioner (GP), who took good care of the patient in the form of
      giving good information about health and social possibilities, and an empathic
      attitude toward these hard-pressed clients, were important factors. The odds
      ratio for a nonbeneficial outcome of the rehabilitation programme, among those
      who had changed GP and reported poor case treatment by the GP, was 3.9 (95% CI;
      1.3-11.9). Additional findings were an association between a desire to go on
      early retirement pension, higher age, and self-estimated poorer health at
      baseline, and actual status as pensioner 9 months after the programme. Predictors
      of a beneficial outcome from the 8-week rehabilitation programme included good
      and comprehensive care-taking in particular by the clients' GP. The presence of a
      high level of symptoms and complaints of pain and stress had no effect on the
      outcome of rehabilitation in this cohort.

PMID- 15844680
TI  - Safety issues in functional capacity evaluation: findings from a trial of a new
      approach for evaluating clients with chronic back pain.
AB  - Although safety is recognized as a critical issue in functional capacity
      evaluations (FCEs), it has rarely been investigated. This paper reports on the
      findings of a study which examined safety aspects of a new approach to FCE.
      Fourteen rehabilitation clients with chronic back pain participated in the study.
      Aspects examined included the pre-FCE screening procedures, the monitoring of
      performance and safety during the FCE, and the end of FCE measures and follow-up
      procedures. Support was found for the screening procedures of the approach,
      particularly blood pressure measurement, and for the combined approach to
      monitoring of the person's performance from biomechanical, physiological and
      psychophysical perspectives. Issues for FCE safety in general are identified and
      discussed, including the importance of screening procedures to determine
      readiness for FCEs and the issue of load handling in FCEs, especially in relation
      to clients with chronic back pain.

PMID- 15844682
TI  - Is CBT already the dominant paradigm in psychotherapy research and practice?

PMID- 15844681
TI  - Assessment of functional capacity of the musculoskeletal system in the context of
      work, daily living, and sport: a systematic review.
AB  - The aim of this systematic review was to survey methods to assess the functional
      capacity of the musculoskeletal system within the context of work, daily
      activities, and sport. The following key words and synonyms were used: functional
      physical assessment, healthy/disabled subjects, and instruments. After applying
      the inclusion criteria on 697 potential studies and a methodological quality
      appraisal, 34 studies were included. A level of reliability > 0.80 and of > 0.60
      resp 0.75 and 0.90, dependent of type of validity, was considered high. Four
      questionnaires (the Oswestry Disability Index, the Pain Disability Index, the
      Roland-Morris Disability Questionnaire, and the Upper Extremity Functional Scale)
      have high levels on both validity and reliability. None of the functional tests
      had a high level of both reliability and validity. A combination of a
      questionnaire and a functional test would seem to be the best instrument to
      assess functional capacity of the musculoskeletal system, but need further
      examined.

PMID- 15844683
TI  - Cognitive assessment of social anxiety: a comparison of self-report and thought
      listing methods.
AB  - The goal of the present study was to compare 2 cognitive assessment methods for
      social anxiety: a thought listing and a self-report method. The focus of this
      study was on the convergent and divergent validity of these methods using a multi
      trait multi-method approach. Furthermore, treatment sensitivity was explored.
      Fifty-eight patients with social phobia completed thought listings followed by 2
      different social stress tasks before and after an exposure group treatment (n =
      33), or following a waiting period (n = 25). One task consisted of speaking in
      front of 2 confederates while the other task involved initiating a conversation
      with an opposite-sex confederate. Two questionnaires measuring positive and
      negative self-statements regarding public speaking and social interactions were
      also completed. To compare the balance of positive and negative thoughts, the
      State of Mind ratio [positive thoughts/(positive+negative thoughts)] was
      calculated for both cognitive assessment methods. Results demonstrate that
      methods related to social interaction anxiety showed better convergent validity
      than methods related to public speaking anxiety; however, public speaking methods
      captured treatment effects better than methods related to social interaction
      anxiety. This study questions the common assumption that different cognitive
      assessment methods measure the same construct.

PMID- 15844684
TI  - Screening people with anxiety/depression for suitability for guided self-help.
AB  - The aim of this study was to test a questionnaire for screening people with
      anxiety/ depression for their suitability for certain forms of computer-guided
      self-help. A total of 196 referrals completed the screening questionnaire. Three
      clinicians each independently judged the referrals' broad problem type and
      suitability. Referrals were randomized to 1 of 3 clinicians for a screening
      interview. The results show that inter-clinician agreement was good for
      questionnaire-based problem type and suitability, and excellent for screening
      interview-based problem type and suitability. Agreement between the questionnaire
      and interview was good on problem type but poor on suitability. Compared with the
      screening interview, the questionnaire detected suitable patients well but
      unsuitable patients less well. In conclusion, by quickly scanning the completed
      questionnaire, clinicians were able sensitively to detect patients' problem types
      that were suitable for certain forms of self-help. Some unsuitability items need
      refining.

PMID- 15844685
TI  - Further examination of the psychometric properties of the comprehensive effects
      of alcohol questionnaire.
AB  - Although the expectancies component of the Comprehensive Effects of Alcohol
      Questionnaire has previously been shown to be factorially valid, the factor
      structure of its valuations component has not previously been examined. The aims
      of this paper were: (i) to replicate the factor structure of the expectancies
      items; (ii) to explore the factor structure of the valuations items; and (iii) to
      investigate the utility of using the Comprehensive Effects of Alcohol
      Questionnaire to predict drinking behavior. The questionnaire was administered to
      1004 university students along with measures of quantity and frequency of alcohol
      consumption. Fromme, Stroot, and Kaplan's (1993) factor structure of the
      expectancies scales was replicated. The factor structures of the negative
      valuations scales were characterized by 2 rather than 3 factors. Negative
      expectancies improved upon the prediction of drinking quantity and frequency over
      and-above positive expectancies, and valuations further improved prediction over
      and-above expectancies. Theoretical and clinical implications are discussed.

PMID- 15844686
TI  - Interoceptive exposure therapy combined with trauma-related exposure therapy for
      post-traumatic stress disorder: a case report.
AB  - Trauma-related exposure therapy is a useful but not universally effective
      treatment for post-traumatic stress disorder. Anxiety sensitivity may play an
      important role in this disorder, as it does in panic disorder. Studies have shown
      that interoceptive exposure therapy reduces anxiety sensitivity in panic
      disorder. The present case study was a preliminary investigation of the merits of
      including interoceptive exposure therapy in the treatment of post-traumatic
      stress disorder, in order to improve treatment outcome for a patient who had no
      history of panic disorder or panic attacks. Interoceptive exposure therapy (4
      sessions) was one component of treatment, combined with trauma-related exposure
      therapy (4 sessions of imaginal exposure followed by 4 sessions of in vivo
      exposure). Treatment outcome was assessed with the Clinician-Administered Post
      traumatic Stress Disorder Scale, a self-report measure of post-traumatic stress
      disorder symptoms, and measures of symptoms and cognitions commonly associated
      with post-traumatic stress disorder. Scores on all outcome measures decreased
      over the course of treatment, with gains maintained at 1- and 3-month follow-up.
      Symptoms of anxiety sensitivity and post-traumatic stress disorder decreased
      during interoceptive exposure therapy. The results indicate that interoceptive
      exposure therapy is a promising adjunctive intervention for post-traumatic stress
      disorder. Further research is needed into the merits of combining interoceptive
      exposure therapy and trauma-related exposure therapy as a means of boosting
      treatment efficacy.

PMID- 15844687
TI  - Intensive cognitive behavioural group treatment for social phobia: a pilot study.
AB  - The aim of this pilot study was to examine the effectiveness of an intensive form
      of cognitive behavioural group treatment practised routinely in a psychiatric
      clinic. A total of 27 outpatients with social phobia of long duration were
      assigned to a 41-hour treatment administered over 2 periods of 3.5 and 4.5 days,
      1 week apart. Four groups, each comprising 6-8 patients, participated in the
      study. All except 1 patient (26/27) completed the treatment and 20 patients
      participated in all follow-up sessions after 3, 6 and 12 months. Treatment
      significantly reduced fear and avoidance of social interaction and performance,
      anticipatory anxiety and symptoms' influence on daily life. Follow-up assessments
      indicated maintained or increased improvement from post-test to 1 year and large
      sensitivity to treatment at both post-test and 1 year. Of the patients in the
      study, 85% were taking a prescribed drug, and 70% had taken medication for at
      least 1 year before they entered the treatment. At 1-year follow-up 52% had
      discontinued medication.

PMID- 15844688
TI  - Hierarchical model of vulnerabilities for anxiety: replication and extension with
      a clinical sample.
AB  - This study served to replicate and extend our previously obtained hierarchical
      model of the relationships among general anxiety vulnerabilities, specific
      anxiety vulnerabilities and specific anxiety manifestations including panic
      symptoms, health anxiety, obsessive-compulsive symptoms and worry. Questionnaires
      assessing these variables, as well as positive affectivity and depressiveness,
      were administered to 125 outpatients seeking treatment for panic disorder, social
      anxiety disorder, obsessive-compulsive disorder, generalized anxiety disorder or
      major depressive disorder. The results, using a clinical sample, were highly
      consistent with the hierarchical model obtained in the previous study using a
      student sample. A more elaborate model, based on published theoretical and
      empirical evidence, was identified and tested, and similar results were obtained.
      Negative affectivity had expected direct positive effects on all of the specific
      anxiety and depression manifestations, with the exception of health anxiety,
      which showed a negative relationship, and OCD symptoms, which showed no
      relationship. Positive affectivity was found to be a specific risk factor for
      depression, while intolerance of uncertainty was found to be a specific risk
      factor for worry and depression. Finally, anxiety sensitivity appears to be a
      significant risk factor for panic and health anxiety.

PMID- 15844689
TI  - Meta-analysis of outcome of cytomegalovirus colitis in immunocompetent hosts.
AB  - There are only a few anecdotal reports of cytomegalovirus (CMV) colitis in
      immunocompetent hosts. The impact of the disease in this patient population
      remains poorly understood. The aim of this study was to perform a meta-analysis
      using individual patient data to determine outcomes of CMV colitis in
      immunocompetent patients and identify risk factors that might influence
      prognosis. A literature search was performed from 1980 to 2003 looking for
      immunocompetent patients with CMV colitis. Immunocompetence was defined as
      absence of congenital or acquired immune deficiency, transplant, or
      immunosuppressive medication. Patients were divided by age (<55 versus > or =55)
      and grouped according to coexisting illnesses. Kaplan-Meier curves were plotted
      to assess survival. Variables included age, sex, site of acquisition of
      infection, extent of disease, coexisting illnesses, and treatment modality. A
      total of 44 patients were identified, with an average age of 61.1. Only 10 were
      free of any comorbidity. The mean follow-up was 13.4 months. Spontaneous
      remission occurred in 31.8%, mostly individuals <55 years old. Fourteen deaths
      occurred, all of which were in patients >55. There was a higher mortality rate
      among male patients > or =55 (56.9%; P = 0.08), patients with immune-modulating
      diseases (75.2%; P = 0.10), and those having a colectomy (68.9%; P = 0.09). This
      analysis underlines the rarity of CMV colitis in patients with an intact immune
      system. Advanced age, male gender, presence of immune-modulating comorbidities,
      and need for surgical intervention are factors negatively influencing survival.
      Conversely, young healthy patients have a good prognosis with no intervention.

PMID- 15844690
TI  - HIV enteropathy: undescribed ultrastructural changes of duodenal mucosa and their
      regression after triple antiviral therapy. A case report.

PMID- 15844691
TI  - Comparison of proton pump inhibitor-based triple therapy with losec and the
      generic drug, Omepradex, for efficacy of Helicobacter pylori eradication.
AB  - Triple therapy with a proton pump inhibitor (PPI), amoxicillin, and
      clarithromycin is widely accepted in Israel for Helicobacter pylori eradication.
      Recently, a generic drug for omeprazole was introduced to the market, but its
      efficacy as a PPI was questioned. The aim of the study was to compare eradication
      efficacy of triple therapy-based regimens with Losec (Astra-Zeneca, Sweden) and
      the generic form, Omepradex (Dexxon, Israel). People belonging to Clalit Health
      Services (CHS), the biggest health insurance provider in Israel, and receiving
      omeprazole (Losec or Omepradex) for 7 days (assumed to be Helicobacter pylori
      eradication purposes), between 1.1.2001 and 31.12.2001, were retrieved from the
      CHS central computer. Of 450 patients (287 in the Losec group and 163 in the
      Omepradex group), 97 (21.6%) underwent 13C-urea breath test (13CUBT) for
      validation of Helicobacter pylori successful eradication and participated in the
      study. They were all treated with triple therapy with omeprazole, amoxicillin,
      and clarithromycin, and were stratified according to the PPI used: Group A,
      Losec; and Group B, Omepradex. Positivity of 13CUBT was computed. Sixty-one
      (21.25%) and 36 (22.08%) patients in Groups A and B, respectively, underwent 13
      CUBT for validation of successful Helicobacter pylori eradication (NS). In Group
      A 41 of 61 patients (67.21%) had a negative 13CUBT, in comparison with 26 of 36
      (72.22%) in Group B (NS). Using logistic regression analysis all confounding
      factors were found to be noncontributory to the discrimination between negative
      (successful eradication) and positive (failed eradication) 13CUBT. There is no
      statistically significant difference between Losec and the generic drug Omepradex
      as part of a PPI-based triple therapy for eradication efficacy of Helicobacter
      pylori.

PMID- 15844692
TI  - Effect of high-dose aspirin on Helicobacter pylori eradication.
AB  - We conducted a pilot study aimed at comparing the efficacy of the standard OAC
      (omeprazole-amoxicillin-clarithromycin) regimen with a combination of the OAC
      regimen and aspirin (OACA). Follow-up endoscopic findings showed that the
      previous ulcers were completely healed in all subjects. The eradication rates
      (per protocol) were 80.3% (49/61) in the OAC group and 86.7% (52/60) in the OACA
      group. The eradication rate was not significantly different between the two
      groups. The most common adverse event was a bad taste, and the overall adverse
      events were similar in the two groups. The combination of the OAC regimen and
      aspirin was not significantly superior to the standard OAC regimen, but it was
      well tolerated in a group of patients with peptic ulcer disease. Its potential
      for clinical use to augment the efficacy of H. pylori eradication may warrant
      further investigation.

PMID- 15844693
TI  - Efficacy and tolerability of rifampicin-based rescue therapy for Helicobacter
      pylori eradication failure in peptic ulcer disease.
AB  - In vitro activity of rifampicin has been shown against H. pylori. It has also
      been reported that the prevalence of H. pylori is low in patients with
      tuberculosis treated with rifampicin. Clinical trials are required to establish
      the efficacy of rifampicin as a salvage therapy for eradication of H. pylori. We
      aimed to evaluate the efficacy of rifampicin-based salvage therapy for
      eradication of H. pylori in patients with peptic ulcer disease. Twenty-eight
      patients with peptic ulcer disease who either had failed eradication of H. pylori
      or had a recurrence of H. pylori following successful eradication were included
      in the prospective study. The inclusion criteria included one or more failed
      attempts at eradication and presence of H. pylori infection as evidenced by
      positivity of at least two of three tests: rapid urease test (RUT), 14C urea
      breath test (UBT), and histology. The subjects were treated with a 10-day regimen
      consisting of rifampicin, 450 mg od, tetracycline, 1 g bd, and esomeprazole, 40
      mg bd. Four weeks after completion of therapy, H. pylori status was assessed by
      RUT, 14C, UBT, and histology. Liver function tests were done before and at the
      end of therapy. The study subjects included 25 males and 3 females with a mean
      age of 33.7+/-8.92 years (range: 22-65 years). The median duration of symptoms
      was 42 months, with a range of 1-180 months. The median number of eradication
      attempts was two, with one prior attempt in 6 (21.4%), two attempts in 19
      (67.9%), and three attempts in 3 (10.7%) patients. Successful H. pylori
      eradication as defined by concomitant negativity of RUT, UBT, and histology with
      special stains was achieved in 32.1% (9/28) of patients by intention-to-treat and
      33.3% (9/27) of patients by per-protocol analysis. This pilot study suggests that
      rifampicin-based regimes have no role as salvage eradication therapy in
      refractory cases of H. pylori infection with peptic ulcer disease.

PMID- 15844694
TI  - High eradication rates of Helicobacter pylori infection with first- and second
      line combination of esomeprazole, tetracycline, and metronidazole in patients
      allergic to penicillin.
AB  - H. pylori eradication is a challenge in patients allergic to penicillin, both
      first-line and failures of prior therapy. We aimed to assess the eradication rate
      of H. pylori in patients allergic to penicillin, first-line and failures of prior
      therapy, the efficacy of healing of active duodenal ulcer disease (DUD) and
      erosive gastritis, and the safety and tolerability of the combination. Twenty
      patients with documented allergy to penicillin, DUD, and H. pylori infection, 17
      (85%) for first-line treatment and 3 (15%) prior therapy failures, were given a
      10-day regimen of esomeprazole, 40 mg qid, tetracycline, 500 mg qid, and
      metronidazole, 500 mg qid. Baseline and follow-up panendoscopy > or =30 days
      after end of treatment was performed for rapid urease test (Clotest), and four
      site biopsies for H. pylori, and to document endoscopic peptic ulcer disease. All
      adverse events during treatment were documented. Eradication rates by intention
      to treat (ITT) were 85% for first-line treatment and 100% for failures. Seventy
      percent of all cases had a normal endoscopy at follow-up, and 85 and 100% of
      patients had healed erosive gastritis and DUD, respectively, from baseline. There
      were histological improvements in most patients. A high eradication rate was
      obtained even in patients who had a shorter duration of treatment. The
      combination was well tolerated. A combination of esomeprazole, tetracycline, and
      metronidazole is effective for eradication of H. pylori in patients allergic to
      penicillin, for both first-line treatment and failures of prior treatment.

PMID- 15844695
TI  - Acid challenge to the esophageal mucosa: effects on local nitric oxide formation
      and its relation to epithelial functions.
AB  - To evaluate the effect of esophageal acid exposure on epithelial function,
      transmucosal potential, histopathological markers of acute tissue damage, and
      local nitric oxide production were examined in healthy volunteers treated with
      proton pump inhibitors (group I), patients with treated reflux disease (group
      II), and patients with untreated erosive reflux disease (group III). The
      participants were randomized to esophageal perfusion with either saline or HCl.
      Denominators of acute acid exposure were balloon cells in superficial layers and
      superficial densification. The nitric oxide concentrations in groups I to III
      increased from < 1, 10.0+/-10.0, and 20.6+/-19.9 ppb, respectively, to 300+/-80,
      1360+/-1080, and 920+/-700 ppb after HCl infusion (P < 0.001). Inducible nitric
      oxide synthase was consistently expressed in the epithelium. Blood flow was lower
      among reflux patients but did not correlate with acid exposure or nitric oxide.
      Nitric oxide is formed following acid perfusion and predominantly in
      gastroesophageal reflux disease.

PMID- 15844696
TI  - A retrospective review of enteroclysis in patients with obscure gastrointestinal
      bleeding and chronic abdominal pain of undetermined etiology.
AB  - Our purpose was to determine the diagnostic utility of enteroclysis in the
      evaluation of obscure gastrointestinal bleeding and abdominal pain of unknown
      etiology. This is a retrospective review of 97 consecutive patients (mean age,
      54.1+/-17.5 [SD] years; 49 male and 48 female) who underwent enteroclysis at
      Temple University Hospital from January 1994 to October 2001 for the evaluation
      of obscure GI bleeding or chronic abdominal pain of undetermined etiology. Prior
      to enteroclysis all patients had an EGD and colonoscopy, which were nondiagnostic
      for their symptoms. Sixty-three patients (64.9%) had enteroscopy performed prior
      to enteroclysis that was also negative. Enteroclysis results were defined as
      positive based on anatomical or functional abnormalities. Analysis of the data
      included the percentage yield of positive exams, the percentage of positive
      results per symptom category, and the percentage of patients with a change in
      clinical management based on positive enteroclysis results. Ninety-seven patients
      underwent enteroclysis. The indications for enteroclysis were obscure GI bleeding
      in 67 patients (69.1%) and chronic abdominal pain in 30 patients (30.9%). The
      number of positive exams was 19 (19.6%). Fourteen of the 67 patients with the
      indication of GI bleeding had a positive exam (21%), while 5 of the 30 patients
      with chronic abdominal pain had a positive result (16.7%). There was a change in
      clinical management due to the enteroclysis results in 10 patients: 7 patients
      with GI bleeding (10%) and 3 patients with chronic abdominal pain (10%). Positive
      enteroclysis findings included adhesions (7), filling defects and masses (5),
      strictures (2), small bowel diverticulosis (1), mucosal abnormalities (3), and a
      motility disorder (1). The overall positive yield for enteroclysis was 19.6%,
      with a yield of 16.7% for chronic abdominal pain and 21% for gastrointestinal
      bleeding. Enteroclysis results changed the clinical management in approximately
      10% of the patients.

PMID- 15844697
TI  - Attitudes and referral patterns of primary care physicians when evaluating
      subjects with noncardiac chest pain--a national survey.
AB  - Noncardiac chest pain (NCCP) may affect up to 23% of the U.S. population. The
      clinical approach and referral patterns of primary care physicians (PCPs) when
      evaluating NCCP subjects are unknown. We aimed to determine the preferences of
      diagnostic tests, referral patterns, and treatment plans of NCCP patients by
      PCPs. PCPs were randomly selected from the American Medical Association national
      membership list. A 24-item questionnaire was mailed, which focused on demographic
      information, characteristics of practice, preferences of diagnostic tests,
      referral patterns, and treatment plans. Two hundred five (40%) PCPs returned the
      questionnaire (mean age, 49; 77% males; practice type--community-based, 40.5%;
      hospital-based, 10.7%; and combined, 47.3%; physician type--internists, 46.3%;
      family physicians, 44.4%; general practitioners, 4.9%; and others, 2.9%). The
      mean number of NCCP patients seen in the past 6 months was 108 (6.4% of total
      patients) and 79.5% were treated primarily by PCPs. The three most common
      diagnostic tests used were empirical proton pump inhibitor (PPI) trial (45.6%),
      chest radiograph (39.9%), and upper endoscopy (18.7%). Most PCPs reported that
      they are either comfortable (44.6%) or very comfortable (21.2%) in diagnosing
      NCCP. The three most commonly used therapeutic modalities for NCCP were PPIs
      (37.8%), lifestyle modification (33.7%), and H2 blockers (12.4%). Of those NCCP
      patients referred to a subspecialist, most ended up in gastroenterology (75.6%),
      followed by cardiology (7.8%) and pulmonary (1.6%) clinics. We conclude that most
      PCP's diagnose and treat NCCP patients without referring them to a
      gastroenterologist. However, diagnostic and treatment strategies may not follow
      the current understanding and knowledge of the disorder.

PMID- 15844698
TI  - Two-channel gastric electrical stimulation accelerates delayed gastric emptying
      induced by vasopressin.
AB  - The aim of this study was to investigate the effects of two-channel gastric
      electrical stimulation (GES) on delayed gastric emptying, gastric dysrhythmias,
      and motion sickness-like symptoms induced by vasopressin. Seven dogs implanted
      with four pairs of gastric electrodes and a duodenal cannula were studied in four
      randomized sessions (saline, vasopressin, single-channel GES, and two-channel
      GES). The experiment in each session was conducted sequentially as follows: 30
      min baseline, ingestion of a liquid meal, 30-min iv infusion of vasopressin or
      saline, and two 30-min postprandial recordings. In the GES sessions, GES was
      applied via the first pair of electrodes for single-channel GES or the first and
      third pairs of electrodes for two-channel GES. Gastric emptying was collected
      every 15 min via the cannula for a period of 90 min. Results were as follows. (1)
      Vasopressin induced gastric dysrhythmias, motion sickness-like symptoms, and
      delayed gastric emptying (P < 0.01, ANOVA). (2) GES normalized gastric
      dysrhythmias (P < 0.01) but showed no effects on vasopressin-induced emetic
      response. (3) Two-channel GES improved delayed gastric emptying induced by
      vasopressin. In comparison with the vasopressin session, two-channel GES, but not
      single-channel GES, significantly increased gastric emptying at 30 min (43.9+/
      12.6 vs. 27.5+/-7.7%; P < 0.03), 60 min (75.3+/-15.1 vs. 54.0+/-17.8%; P < 0.05),
      and 90 min (91.6+/-9.8 vs. 80.3+/-9.0%; P < 0.05). GES with long pulses is able
      to normalize gastric dysrhythmias. Two-channel GES improves delayed gastric
      emptying induced by vasopressin.

PMID- 15844699
TI  - The time of peak 13CO2 excretion: what does it really reflect in gastric emptying
      breath tests?

PMID- 15844700
TI  - Effect of aging on transpyloric flow, gastric emptying, and intragastric
      distribution in healthy humans--impact on glycemia.
AB  - The aims of this study were to evaluate (i) the relationship between transpyloric
      flow (TF) assessed by Doppler ultrasonography and scintigraphy, (ii) the effects
      of healthy aging on TF and gastric emptying (GE), and (iii) the relationship
      between the glycemic response to oral glucose and TF. Ten healthy "young" (7 M, 3
      F) and 8 "older" (4 M, 4 F), subjects had simultaneous measurements of TF, GE,
      and blood glucose after a 600-ml drink (75 g glucose labeled with 20 MBq 99mTc
      sulfur colloid) while seated. TF measured by ultrasound was measured during drink
      ingestion and for 30 min thereafter. GE was measured scintigraphically for 180
      min after drink ingestion. Blood glucose was measured before the drink and at
      regular intervals until 180 min. During drink ingestion, TF was greater (P <
      0.05) and GE faster (retention at 60 min: 70.8+/-3.3 vs. 83.8+/-4.6%; P < 0.05)
      in young compared to older subjects. There was no difference in fasting blood
      glucose between the two groups but the magnitude of the rise in blood glucose was
      greater in the young compared to the older subjects; (at 15 min 2.4+/-0.3 vs.
      1.5+/-0.5 mmol/L; P < 0.05). In contrast, after 90 min blood glucose
      concentrations were higher in the older subjects. There were significant
      relationships between the early blood glucose concentration and both TF (e.g., at
      15 min: r = 0.56, P < 0.05) and GE (e.g., at 15 min: r = -0.51, P < 0.05). In
      conclusion, the results of this study indicate that (i) TF is initially less, and
      GE slower, in older compared to young subjects; (ii) the initial glycemic
      response to oral glucose is related to TF; and (iii) measurements of TF by
      ultrasound and scintigraphy correlate significantly.

PMID- 15844701
TI  - Inflammation-related erythrocyte aggregation in patients with inflammatory bowel
      disease.
AB  - Chronic inflammation is associated with increased erythrocyte
      adhesiveness/aggregation. This might have deleterious effects on the
      microcirculatory flow and tissue oxygenation. We aimed to determine the degree of
      erythrocyte adhesiveness/aggregation in the peripheral blood of individuals with
      inflammatory bowel disease (IBD). Fifty-two patients (24 women and 28 men) with
      ulcerative colitis (UC) at a mean age of 44.0+/-16.8 years and 96 patients (44
      women and 52 men) with Crohn's disease (CD) at a mean age of 38.0+/-15.5 years,
      with various degrees of disease activity, were matched to normal controls. A
      simple slide test and image analysis were used to determine the degree of
      erythrocyte adhesiveness/aggregation. CD activity index (CDAI) was determined in
      patients with CD, while clinical colitis activity index was applied for patients
      with UC. A significant (P < 0.0005) increment in the degree of erythrocyte
      adhesiveness/aggregation was noted in both groups of IBD patients compared with
      matched control groups. This increment was evident even in individuals with a low
      index of disease activity and during remission. The highly significant
      correlation with the concentrations of fibrinogen suggests that the degree of
      erythrocyte adhesiveness/aggregation is an inflammation-related phenomenon. An
      enhanced state of erythrocyte adhesiveness/aggregation was noted in the
      peripheral blood of patients with IBD. This might have a deleterious effect on
      intestinal microcirculatory flow and tissue oxygenation.

PMID- 15844702
TI  - Antecedent ethanol ingestion prevents postischemic leukocyte adhesion and P
      selectin expression by a protein kinase C-dependent mechanism.
AB  - The aim of this study was to determine whether protein kinase C (PKC) contributed
      to the effects of ethanol ingestion to prevent P-selectin expression, leukocyte
      rolling (LR), and stationary leukocyte adhesion (LA) induced by subjecting the
      small bowel to ischemia and reperfusion (I/R) 24 hr later. I/R increased P
      selectin expression, LR, and LA, effects that were largely abolished by
      antecedent ethanol consumption. Exposing the bowel to a specific but nonisoform
      selective PKC inhibitor (chelerythrine or bisindolylmaleimide I) during the
      period of ethanol exposure did not alter the anti-inflammatory effects induced by
      ethanol ingestion 24 hr prior to I/R. Go-6976, a PKC inhibitor that exhibits a
      high degree of selectivity for the calcium-dependent PKC isoforms, markedly
      reduced the effectiveness of antecedent ethanol exposure to abrogate these
      postischemic inflammatory responses. Our data indicate that antecedent ethanol
      exposure prevents postischemic P-selectin expression, LR, and LA by a mechanism
      that involves activation of calcium-dependent PKC isotypes.

PMID- 15844703
TI  - Digital ischemia associated with squamous cell carcinoma of the esophagus.

PMID- 15844704
TI  - Elevated CA 19-9 caused by Hashimoto's thyroiditis: review of the benign causes
      of increased CA 19-9 level.

PMID- 15844705
TI  - Systemic iron supplementation replenishes iron stores without enhancing colon
      carcinogenesis in murine models of ulcerative colitis: comparison with iron
      enriched diet.
AB  - Ulcerative colitis (UC) patients frequently require iron supplementation to
      remedy anemia. The impact of systemic iron supplementation (intraperitoneal
      injection) on UC-associated carcinogenesis was assessed in mice subjected to
      cyclic dextran sulfate sodium (DSS) treatment and compared with dietary iron
      enrichment. Systemic iron supplementation, but not a twofold iron diet, remedied
      iron deficiency as indicated by the histochemical detection of splenic iron
      stores. A twofold iron diet, but not systemic iron, increased iron accumulation
      in colonic luminal contents, at the colonic mucosal surface, and in superficial
      epithelial cells. Colitis-associated colorectal tumor incidence after 15 DSS
      cycles was not affected by systemic iron (2/28; 7.1%) compared to nonsupplemented
      controls (4/28; 14.1%) but was significantly increased by the twofold iron diet
      (24/33; 72.7%) (P < 0.001). Mechanistic study revealed that systemic iron had no
      effect on DSS-induced inflammation, or colonic iNOS and COX-2 protein levels,
      compared to controls. Systemic iron supplementation for 16 weeks replenished
      splenic iron in a spontaneous colitis model (interleukin-2-deficient mice) and
      significantly reduced colonic inflammation compared to interleukin-2 (-/-)
      controls without increasing hyperplastic lesions. These results suggest that iron
      supplemented systemically could be used to remedy anemia in UC patients without
      exacerbating inflammation or enhancing colon cancer risk. These findings need to
      be verified in clinical studies.

PMID- 15844706
TI  - Differential labeling by monoclonal antibodies Adnab-9 and anti-alpha-defensin 5
      based on the distribution and adenomatous tissue content of colonic polyps.
AB  - We sought a correlation between site and morphology of colonic polyps by labeling
      with neoplastic and general Paneth cell markers, monoclonal antibodies Adnab-9
      and anti-alpha-defensin 5, respectively. Proportions labeled by Adnab-9 and anti
      alpha-defensin 5 were, respectively, 42 and 85% for adenomas, 39 and 63% for
      early tubular adenomas, 41 and 44% for serrated, 34 and 20% for mixed, and 11
      versus 2.7% for hyperplastic polyps. Compared with hyperplastic polyps, the
      proportion of other polyps labeled by Adnab-9 or anti-alpha-defensin 5 was higher
      but this difference was more significant for distal (P = 0.008 for Adnab-9 and P
      = 0.0001 for anti-alpha-defensin 5) than proximal (P = 0.645 and P = 0.154,
      respectively) polyps. While increased labeling of all proximal polyps compared to
      distal ones mirrored the colonic distribution of Paneth cells, distal adenomas
      tended to have a higher proportion labeled by Adnab-9, suggesting that Adnab-9
      labels Paneth cells associated with increased neoplastic potential.

PMID- 15844707
TI  - Evaluation of The Federal Bureau of Prisons protocol for selection of which
      hepatitis C-infected inmates are considered for treatment.
AB  - The Federal Bureau of Prisons limits hepatitis C therapy to those inmates with
      certain biochemical abnormalities. To evaluate this protocol, an analysis was
      done on data collected on hepatitis C infected inmates in the Louisiana
      Department of Corrections. A quality assurance database of hepatitis C infected
      inmates evaluated in the Louisiana Department of Corrections was reviewed for
      liver biopsy and laboratory results. Patients were compared as to whether they
      would have been biopsied under the Federal Bureau of Prisons protocol and if
      there were histologic differences between those who would and those who would not
      have been biopsied. Of 490 inmates biopsied, 26% (129) had an alanine
      aminotransferase level between one and two times the upper limit of normal
      without other biochemical abnormalities. If treating stages 2-4, 48% of these
      would qualify for treatment (15% if treating stages 3-4). There was no
      statistical difference between this group and either the group with an alanine
      aminotransferase level between one and two times the upper limit of normal and
      with other laboratory abnormalities or the group with an alanine aminotransferase
      level greater than or equal to two times the upper limit of normal and without
      other abnormalities. In the Louisiana Department of Corrections, the Federal
      Bureau of Prisons protocol was neither sensitive nor specific enough at
      identifying those that should be considered for hepatitis C therapy.

PMID- 15844708
TI  - Peginterferon alpha-2a combination therapies in chronic hepatitis C patients who
      relapsed after or had a viral breakthrough on therapy with standard interferon
      alpha-2b plus ribavirin: a pilot study of efficacy and safety.
AB  - There are no established therapeutic regimens for hepatitis C virus (HCV)
      patients who relapse following treatment with interferon alpha-2b and ribavirin
      or those who break through while on interferon alpha-2b and ribavirin. We
      therefore evaluated various combination therapies in HCV patients who relapsed or
      experienced a viral breakthrough. Patients (n = 124) were randomized to 48 weeks
      of treatment with once-weekly subcutaneous injections of 180 microg pegylated
      (peg-) interferon alpha-2a plus oral ribavirin (800-1000 mg/day), mycophenolate
      mofetil (2 g/day), amantadine (200 mg/day), or ribavirin and amantadine and
      followed for an additional 24 weeks. The sustained virologic response was higher
      in patients administered peginterferon alpha-2a plus ribavirin (38%) or ribavirin
      and amantadine (45%) than in those administered peginterferon alpha-2a plus
      mycophenolate mofetil (17%) or amantadine (10%). As in previous studies, patients
      with genotype non-1 and those with lower viral loads had better responses than
      those with genotype 1 and high viral loads, though the differences did not reach
      significance. The four treatment regimens had similar safety profiles, except
      that patients receiving ribavirin had greater maximal hemoglobin decreases. These
      findings suggest that the combination of peginterferon alpha-2a plus ribavirin or
      with ribavirin and amantadine is effective in some HCV patients who relapse after
      treatment with interferon alpha-2b plus ribavirin.

PMID- 15844709
TI  - Interferon alfacon-1 and ribavirin versus interferon alpha-2b and ribavirin in
      the treatment of chronic hepatitis C.
AB  - Despite advances in the therapy of chronic hepatitis C, a large number of
      patients do not respond to current therapies. The study objective was to assess
      whether a combination of interferon (IFN) alfacon-1 and ribavirin improves the
      response rate compared with a combination of INF alpha-2b and ribavirin in
      chronic hepatitis C subjects. The study was designed as an open-label,
      prospective, randomized, controlled study; 128 subjects with chronic hepatitis C
      were randomized to INF alfacon-1, 15 microg three times per week, plus ribavirin,
      1 g/day, or IFN-alpha2b, 3 million units three times per week, plus ribavirin, 1
      g/day for 48 weeks. The end point of the study was a sustained viral response,
      defined as undetectable HCV RNA at 24 weeks post 48 weeks of treatment. Overall,
      57% of subjects in the INF alfacon-1/ribavirin group achieved a sustained
      antiviral response, compared with 40% of subjects in the IFN-alpha2b/ribavirin
      group (P = 0.052). In the subset of subjects with a high viral load, HCV RNA was
      successfully eradicated in more individuals who received INF alfacon-1/ribavirin
      than subjects who received IFN-alpha2b/ribavirin (57 versus 31%; P = 0.025).
      Among individuals with genotype 1 and a high viral load, the sustained antiviral
      response was significantly higher with INF alfacon-1/ribavirin than with IFN
      alpha2b/ribavirin (46 versus 14%; P = 0.019). Adverse events were similar in both
      treatment groups. In conclusion, this study demonstrated that the combination of
      INF alfacon-1 and ribavirin provides a significantly better treatment response
      compared with the combination of IFN-alpha2b and ribavirin in chronic HCV
      subjects infected with genotype 1 and a high viral RNA load.

PMID- 15844710
TI  - Prevalence of hepatitis C infection in a population of asymptomatic people in a
      checkup unit in Mexico city.
AB  - Hepatitis C virus (HCV) infection has an estimated prevalence of 3% around the
      world. Unfortunately, many persons with HCV infection are asymptomatic. The aim
      of this study was to determine the prevalence of hepatitis C Virus infection in
      asymptomatic persons. This study was carried out in a population-based cross
      sectional study in the Checkup Unit of University Hospital in Mexico City.
      Patients with two or more HCV risk factors were studied. Serum specimens from all
      patients were screened for HCV RNA by qualitative polymerase chain reaction
      (PCR). HCV RNA-positive serum was also screened by quantitative PCR and for HCV
      genotype. Three hundred asymptomatic people were included, 194 men and 106 women,
      with a mean age of 46.8+/-11.9. Six (2%) of the 300 people were positive and
      viremic. The most common risk factors in positive patients were manicures or
      pedicures with a nonpersonal instrument and more than three sexual partners. We
      concluded that hepatitis C is frequent in asymptomatic people, and those people
      are often viremic. In addition, this study suggests that the spectrum of liver
      disease in asymptomatic and newly diagnosed HCV-positive persons is broad.

PMID- 15844711
TI  - Role of melatonin in reducing water avoidance stress-induced degeneration of the
      liver.
AB  - Melatonin, a pineal secretory product, is a potent scavenger of a variety of free
      radicals. We investigated the role of melatonin on water avoidance stress (WAS)
      induced degenerations of the liver parenchyme. Wistar albino rats were exposed to
      acute WAS (aWAS group) or chronic WAS (cWAS group). Before exposing animals to
      acute (aWAS + mel group) or chronic WAS (cWAS + mel group), 10 mg/kg melatonin
      was injected i.p. The liver samples were investigated under light and
      transmission electron microscope. Malondialdehyde (MDA) and glutathione (GSH)
      levels were also determined. Prominent vascular congestion and dilated sinusoids,
      activated Kupffer cells with prominent morphology, dilated granular endoplasmic
      reticulum membranes, and focal picnotic nuclei were observed in the aWAS group;
      these morphological changes were severe in the cWAS group. MDA level was
      increased and GSH level was decreased significantly in the cWAS group. The
      morphology of liver parenchme in both the aWAS + mel and the cWAS + mel group
      showed that melatonin significantly reduced the degeneration in liver; besides, a
      significant decrease in MDA and an increase in GSH levels were observed in the
      cWAS + mel group. Based on the results, melatonin treatment significantly
      prevented WAS-induced morphological and biochemical changes in liver parenchyma.

PMID- 15844712
TI  - Therapeutic effects and possible mechanisms of a snake venom preparation in the
      fibrotic rat liver.
AB  - The effects of a Chinese snake venom preparation from Agkistrodon halys pallas,
      used for treatment of hepatic fibrosis/cirrhosis in China, was investigated in an
      in vivo rat model and using in situ hepatic perfusion. Four groups were used in
      the experiments: (i) healthy, (ii) healthy/venom-treated, (iii) carbon
      tetrachloride (CCl4)-treated, and (iv) CCl4/venom-treated. Treatment effects were
      assessed by determining hepatic histopathology, biochemistry and fibrosis index
      parameters, bile production, biliary taurocholate recovery, hepatic mRNA
      expression of four bile salt transporters (Ntcp, Bsep, Oatp-1, and Oatp-3),
      comparison of hepatic microcirculation, fibrinolytic activity, and antithrombotic
      effects. Liver histopathology, biochemistry, and fibrosis index showed a dramatic
      improvement in venom-treated animals. There were significant differences in bile
      production between healthy/venom-treated and all other experimental groups and
      between CCl4/venom-treated and CCl4-treated animals, but no significant
      differences were found between CCl4/venom-treated and healthy animals. Biliary
      taurocholate recovery was significantly increased in healthy/venom-treated and
      CCl4/venom-treated animals. The expression of mRNA levels of the four bile salt
      transporters showed an increase after venom treatment. The hepatic
      microcirculation studies showed normalized sinusoidal beds in CCl4/venom-treated
      animals compared to healthy animals, whereas CCl4-treated animals showed abnormal
      profiles to the healthy and the CCl4/AHPV-treated animals. The fibrinogen and
      plasma thromboxane B2 levels of healthy rats decreased with increasing dose after
      venom treatment. It was concluded that snake venom treatment may be therapeutic
      in treatment of hepatic fibrosis/cirrhosis by possibly a combination of increased
      bile flow and improved hepatic microcirculation, changes in bile salt transporter
      expression, and fibrinolytic and antithrombotic effects of the snake venom
      preparation.

PMID- 15844713
TI  - MELD score does not discriminate against patients with hepatic encephalopathy.
AB  - Hepatic encephalopathy (HE) is a significant complication of cirrhosis and part
      of the CTP score. The UNOS database was queried for listings from February 2001
      to February 2002 (CTP era) and February 2002 to February 2003 (MELD era). HE at
      listing, Grade III/IV HE at transplant, and 12-month posttransplant survival were
      compared. HE rate at listing was similar, whereas Grade III/IV HE at time of
      transplant was significantly lower in the MELD era. Waiting periods were shorter
      in the MELD era. Twelve-month posttransplant survival was lower in all patients
      with HE at listing (P < 0.0001) and for patients with Grade III/IV HE at
      transplant (P < 0.0001) in both eras. No significant change in posttransplant
      survival of HE patients was observed after MELD implementation. We conclude that
      (1) HE patients have worse posttransplant survival even after MELD; (2) MELD
      allows more rapid transplantation; and (3) rates of HE at listing have not
      changed since MELD implementation; however, rates of Grade III/IV HE at
      transplant have decreased.

PMID- 15844714
TI  - Successful treatment of sepsis with polymyxin b-immobilized fiber hemoperfusion
      in a child after living donor liver transplantation.

PMID- 15844715
TI  - Do interventions which reduce colonic bacterial fermentation improve symptoms of
      irritable bowel syndrome?
AB  - Abnormal fermentation may be an important factor in irritable bowel syndrome
      (IBS). Gastroenteritis or antibiotic therapy may damage the colonic microflora,
      leading to increased fermentation and the accumulation of gas. Gas excretion may
      be measured by whole-body calorimetry but there has only been one such study on
      IBS to date. We aimed to assess the relationship between IBS symptoms and
      fermentation rates in IBS. A purpose-built, 1.4-m3, whole-body calorimeter was
      used to assess excretion of H2 and CH4 in IBS subjects while consuming a standard
      diet and, again, after open randomization on either the standard diet together
      with the antibiotic metronidazole or a fiber-free diet to reduce fermentation.
      Metronidazole significantly reduced the 24-hr excretion of hydrogen (median value
      compared to the control group, 397 vs 230 ml/24 hr) and total gas (H2 + CH4; 671
      vs 422 ml/min) and the maximum rate of gas excretion (1.6 vs 0.8 ml/min), as did
      a no-fiber polymeric diet (hydrogen, 418 vs 176 ml/min; total gas, 564 vs 205
      ml/min; maximum rate of gas excretion, 1.35 vs 0.45 ml/min), with a significant
      improvement in abdominal symptoms. IBS may be associated with rapid excretion of
      gaseous products of fermentation, whose reduction may improve symptoms.

PMID- 15844716
TI  - Leukocytapheresis (LCAP) for management of fulminant ulcerative colitis with
      toxic megacolon.
AB  - Leukocytapheresis (LCAP) is a method of therapeutic apheresis to remove patients'
      peripheral leukocytes by extracorporeal circulation. Previous studies showed that
      LCAP for the treatment of ulcerative colitis (UC) was more effective and had
      fewer adverse effects compared to high-dose steroid therapy. However, there are
      no reports on the application of LCAP for UC patients with toxic megacolon (TM).
      This study reports the effectiveness and safety of LCAP in treating patients with
      severe or fulminant UC with TM. Six patients were enrolled in this study and LCAP
      sessions were performed three times per week for 2 weeks, followed by four
      further times in the next 4 weeks. After completion of therapy, four patients
      improved in TM and went into the remission stage of UC. The average Rachmilewitz
      clinical activity index of these four patients improved from 19.5 to 1. The
      remaining two patients had to undergo colectomy, however, the symptoms had been
      mitigated by LCAP and the operations were completed without any problems. These
      results suggest that LCAP is an additional effective and safe option for TM
      management in preventing colectomy or for bridging to a safer operation.

PMID- 15844717
TI  - Endovascular treatment of segmental ischemic colitis.

PMID- 15844718
TI  - Insulin-like growth factor binding protein 3 in inflammatory bowel disease.
AB  - Epithelial cell growth regulation has been reported to be altered in inflammatory
      bowel disease (IBD) patients. The cell growth regulatory factor, insulin-like
      growth factor binding protein 3 (IGFBP-3), may be partly responsible for this
      phenomenon. So far, IGFBP-3 levels have been assessed as values of total protein,
      which is a sum of bioactive intact 43- to 45-kDa protein and its inactive
      proteolytic cleavage fragments. We aimed to assess the levels of intact IGFBP-3
      and its cleaving protease MMP-9 in IBD. Patients with IBD and controls were
      included. Total plasma IGFBP-3 concentration was measured in ELISA. Western blot
      analysis, which distinguishes between intact and cleaved IGFBP-3, was performed
      in order to determine the ratio of intact to total protein; this ratio was used
      to calculate the concentration of intact IGFBP-3. The profile of plasma proteases
      was evaluated in zymography and MMP-9 levels were determined in ELISA. The
      concentration of intact IGFBP-3 was significantly decreased in patients with
      moderate to severe IBD activity compared to those in remission or controls. Of
      note, a dramatic depletion of intact IGFBP-3 was found in 7.4% of patients with
      IBD. Zymography revealed that the dominant gelatinase was the pro-form of MMP-9.
      However, no differences in MMP-9 levels were noted between those with active
      disease and controls. The level of intact IGFBP-3 is decreased in IBD patients
      with moderate to severe disease activity. This decrease may be linked to altered
      IGFBP-3 production or to increased cleavage by proteases other than MMP-9.

PMID- 15844719
TI  - Intestinal permeability in long-term follow-up of patients with celiac disease on
      a gluten-free diet.
AB  - Intestinal permeability is frequently abnormal in patients with celiac disease.
      The long-term effect of a gluten-free diet on intestinal permeability and the
      correlation of intestinal permeability with a gluten-free diet are not known. The
      objectives of this study were to determine the responses of intestinal
      permeability and antibody testing to gluten free diet and the degree of
      correlation of these measurements with gluten ingestion. In this prospective
      study, patients with celiac disease were divided into three groups based on
      length of time on a gluten-free diet: Group A, < 1 month; Group B, 1 month-1
      year; Group C, > 1 year. Patients in Groups B and C were tested at baseline and
      at 4-12 weeks later for the following: lactulose/mannitol intestinal
      permeability, endomysial antibody, and 3-day food record. Permeability tests were
      also performed in Group A and control subjects. Intestinal permeability was
      elevated in newly diagnosed celiac disease and in individuals on a gluten-free
      diet for less than 1 year. Intestinal permeability was normal in 80% at visit 1
      and 87% at visit 2 in individuals with celiac disease on a gluten-free diet for
      more than a year. Trace gluten ingestion was associated with increased intestinal
      permeability on visit 2 (P = 0.0480). The sensitivity of detecting gluten
      ingestion as measured by a 3-day food record was higher for permeability testing
      (29 and 36%) compared with endomysial antibody testing (18 and 18%) for visits 1
      and 2, respectively. Intestinal permeability normalizes in the majority of
      individuals with celiac disease on a gluten-free diet. Gluten ingestion as
      measured by a 3-day food record correlates with intestinal permeability
      measurements. The role of permeability testing in the follow-up of patients with
      celiac disease warrants further investigation.

PMID- 15844720
TI  - Natural antibiotic expression in celiac disease--correlation with villous atrophy
      and response to a gluten-free diet.
AB  - As infection influences the pathogenesis and presentation of celiac disease, we
      investigated the expression of natural antibiotics in this condition. Twenty
      three adults were prospectively studied: 10 controls and 13 subjects with
      untreated celiac disease. Distal duodenal biopsies were taken at baseline and
      after 6 months of a gluten-free diet and assessed for the expression of natural
      antibiotics. Epithelial human beta-defensin 1 in subjects with celiac disease had
      a median of 0.02 unit at baseline, compared with 0.34 unit in controls (P <
      0.001). It correlated negatively with the degree of villous atrophy (r = -0.64, P
      = 0.019) and rose to 0.04 unit on the gluten-free diet (P = 0.035 vs. baseline, P
      < 0.001 vs. controls). The expression of other antibiotics was unchanged. The
      expression of epithelial natural antibiotics is limited in celiac disease.

PMID- 15844721
TI  - Serologic testing for celiac disease in young adults--a cost-effect analysis.
AB  - In recent years, there has been a marked increase in the diagnostic workups for
      celiac disease among military personnel, thereby significantly increasing overall
      laboratory testing expenditures and burden. We evaluated the serologic testing
      procedure in symptomatic young adults, using a "cost-effect" approach. We
      evaluated the serologic screening policy for celiac disease among serologically
      tested military personnel. The study population was divided into subgroups
      according to the clinical presentation prior to screening: isolated (low-risk)
      and combined complaints (high-risk). Sensitivity, specificity, and predictive
      values of serologic markers for celiac disease were evaluated. Cost analyses were
      based on diagnostic expenditures. Cost-effect ratio is expressed as cost per
      newly diagnosed patients, and cost minimization as cost per screened individuals.
      Five hundred thirty-eight military personnel were serologically tested for celiac
      disease. Eight new cases of celiac were diagnosed, all of whom belonged to the
      high-risk subgroup and tested positive for at least two positive serologic tests
      (tTG + EMA or tTG + AGA IgG + EMA). EMA Ab measured the highest sensitivity,
      specificity, and predictive values. Average screening expenditure was U.S. $287
      per patient. The lowest cost-effect and cost minimization ratios were achieved by
      implementing a two-step single-marker screening protocol for high-risk subjects
      and one-step follow-up for low-risk subjects. Among patient population of young
      adults, selective diagnostic workup could result in cost-minimization without
      risking quality of diagnosis. From a cost-effect perspective, implemented
      screening procedures need to be dependent on subgroup: low-risk, clinical follow
      up; and high-risk, serological testing for EMA and, only if positive, possibly a
      small-bowel biopsy.

PMID- 15844722
TI  - A short form of the Revised Conflict Tactics Scales, and typologies for severity
      and mutuality.
AB  - The revised Conflict Tactics Scales (CTS2) is the most widely used instrument for
      measuring intimate partner violence. This article presents a short form to enable
      the CTS2 to be used when testing time is very limited. It also presents
      procedures that can be used with either the full test or the short form to
      classify individuals on the basis of severity of behavior toward a partner or by
      a partner, and to classify couples on the basis of mutuality or symmetry in the
      behaviors measured by the CTS2. The results indicate that the short form is
      comparable in validity to the full CTS2. Although the short form does not
      identify as many cases of partner violence as the full scale, it does identify a
      large number of cases and if there is insufficient time for the full scale, can
      be a useful screening instrument.

PMID- 15844723
TI  - Substance use and vulnerability to sexual and physical aggression: a longitudinal
      study of young adults.
AB  - Using data from 2,170 individuals who participated in Waves 8 (age 23) and 9 (age
      29) of a multiyear panel study, this study examined whether alcohol and marijuana
      use in young adulthood increase one's risk for experiencing subsequent sexual or
      physical assault victimization, whether victims' own violent behavior or
      involvement in the sale of drugs explain any effects of substance use on
      victimization, and whether these associations differ by gender. Controlling for
      prior victimization, we found that marijuana use, but not alcohol use, predicted
      women's and men's subsequent sexual victimization and men's subsequent physical
      assault victimization, and that heavy alcohol use, but not marijuana use,
      predicted women's subsequent physical assault victimization. Whereas the links
      from marijuana use to victimization were explained by users' own violent
      behavior, the link from alcohol use to women's physical assault victimization was
      not.

PMID- 15844724
TI  - Men's sexual coercion in intimate relationships: development and initial
      validation of the Sexual Coercion in Intimate Relationships scale.
AB  - We report the development and initial validation of the Sexual Coercion in
      Intimate Relationships Scale (SCIRS), a measure designed to assess the prevalence
      and severity of sexual coercion in committed intimate relationships. We review
      existing measures of sexual coercion and discuss their limitations, describe the
      identification of the SCIRS items, perform a principal components analysis and
      describe the resulting three components, and present evidence for the convergent
      and discriminative validity of the SCIRS. Because sexual coercion in intimate
      relationships often takes the form of subtle tactics, the SCIRS items assess
      communicative tactics such as hinting and subtle manipulations in addition to
      tactics such as the use of physical force. The SCIRS provides researchers and
      clinicians with a valid, reliable, and comprehensive measure with which to study
      the dynamics of sexual coercion in intimate relationships.

PMID- 15844725
TI  - Relationship between peer victimization and school adjustment in sixth-grade
      students: investigating mediation effects.
AB  - Peer victimization is a common occurrence in school settings. This study
      investigated the relationship between peer victimization and school adjustment in
      a sample of 1,022 sixth-grade students. Measures used in this study include peer
      victimization, perceived peer non-support, school attachment, inattention
      problems, and academic achievement. Multivariate path analyses were conducted to
      test direct and mediation effects in the over-all model and to explore gender
      differences. The results provided support for the hypothesized model indicating
      that the relationship between peer victimization and school attachment is
      mediated by perceived peer non-support, and that school attachment is related to
      inattentive school behaviors and poor academic achievement. Paths indicated
      invariance across models for gender. Prevention and intervention implications of
      these findings are discussed.

PMID- 15844726
TI  - Child maltreatment in families experiencing domestic violence.
AB  - This study examined the association between physical domestic violence (PDV) and
      reported child maltreatment in a cohort of children at risk for maltreatment.
      Participants were 219 6- to 7-year-old children and their caregivers. PDV was
      measured by combining caregivers' self-reports and children's reports, while
      child maltreatment was based on state Division of Social Services Central
      Registry records. Among 219 child-caregiver pairs studied, 42 (19.2%) had at
      least one maltreatment report in the 2 years following the interviews. PDV
      consistently predicted child maltreatment, with adjusted odds ratios ranging from
      2.96 to 3.46. In addition, we investigated interactions between PDV and other
      predictors of child maltreatment. Among Aid to Families with Dependent Children
      (AFDC) participants, PDV was highly associated with child maltreatment. However,
      this pattern was not observed among subjects who did not have AFDC. There is an
      increased incidence of child maltreatment reports in families experiencing PDV.
      AFDC participation intensified the probability of child maltreatment in the
      presence of PDV. Findings also suggest that in households experiencing PDV,
      social supports may protect children from maltreatment.

PMID- 15844727
TI  - Sexual assault prevention with college-aged women: a bibliotherapy approach.
AB  - The present research evaluated the efficacy of a skills-based bibliotherapy
      approach to sexual assault prevention for college-aged women. One hundred and ten
      participants were followed prospectively for 16 weeks. A self-help book, written
      by the authors, was compared to a wait-list control on several self-report
      measures. Results revealed significant differences between groups, with
      bibliotherapy participants reporting decreased participation in risky dating
      behaviors and improvement in sexual communication strategies across a variety of
      dating situations. However, results suggested that the self-help book was no more
      effective than the wait-list control in reducing rates of sexual victimization.
      Limitations of the study and directions for future sexual assault prevention
      research with women are discussed.

PMID- 15844728
TI  - Impacts of agency coordination on nonprofit domestic violence and sexual assault
      programs in communities with STOP formula grant funding.
AB  - The goals of the current study are (a) to understand the community and state
      context in which STOP(Services* Training* Officers* Prosecutors)-funded victim
      service (VS) programs operate, (b) to assess the degree to which receipt of STOP
      funding for VS programs and the degree of state-level STOP agency support for
      collaboration among community agencies have led to improved program services and
      community interaction, and (c) to assess the degree to which improved interaction
      between community agencies leads to improvements for VS programs. The results
      show that community interaction between VS programs and other community agencies
      can improve VS program services as reported by service providers. In addition,
      the higher the pre-STOP levels of activity around violence against women issues
      in communities, the more agencies can enhance their service system with STOP
      funding. Also, STOP funding has facilitated greater levels of change for
      communities whose pre-STOP attention to violence against women was lower.

PMID- 15844729
TI  - Identifying the public's knowledge and intention to use human cloning in Greek
      urban areas.
AB  - PURPOSE: The understanding of the public's knowledge on human cloning (HC) and
      its acceptability are considered important for the development of evidence-based
      policy making. The aim of this research study was to investigate the demographic
      and socioeconomic variables that affect the public's knowledge and intention to
      use HC in urban areas of Greece. Additionally, the possible association of
      religiousness with the knowledge and the intention to use HC were also
      investigated. METHODS: Individual interviews were conducted with 1020 men and
      women of urban areas in Greece. Stratified random sampling was performed to
      select the respondents. Several scientists, experts in HC, evaluated the content
      of the instrument initially developed. The final questionnaire was consequently
      the result of a pilot study. RESULTS: Almost half of the respondents (51.5%)
      believed that "HC is a sort of in vitro fertilization" and 42.9% that "it has
      already been applied to human being." They were not aware that "the cloned fetus
      grows in the woman's uterus" (41.5%) and that "HC could regenerate human organs"
      (41.7%). The acceptability of human cloning for the cure of terminal diseases and
      transplantation need is very high (70.7% and 58.6%, respectively). The public's
      intention to have recourse to cloning on the grounds of "bringing" back to life a
      loved person or because of reproductive disorders was reported as desire by 35%
      and 32.5%, respectively. The occupational category (scientists, self-employed,
      and artists), the Intention to use HC, and the number of children are highly
      significant predictors of valid knowledge about HC. Low rates of church
      attendance appeared to relate with high reported Intention to use HC, and
      increasing scores of valid knowledge about HC increased the public's Intention to
      use HC. CONCLUSIONS: A number of specific demographic and socioeconomic
      characteristics and high scores of knowledge provide a persuasive justification
      in demonstrating intention toward HC. The current study suggests that these
      findings should receive further attention by policymakers and scientists within
      the Greek context.

PMID- 15844730
TI  - Area under the curve for estradiol levels do not consistently reflect estradiol
      levels on the day of hCG administration in patients undergoing controlled ovarian
      hyperstimulation for IVF-ET.
AB  - PURPOSE: Most studies reported estradiol (E2) levels attained on day of hCG
      administration when investigating effect of E2 on IVF outcome. We studied whether
      a relationship exists between the area under the curve for E2 levels (AUC-E2) and
      E2 levels on hCG day during IVF-ET. METHODS: Retrospectively, we analyzed data
      for 313 patients who completed one IVF-ET cycle each. Patients were sorted
      according to AUC-E2 levels. Then we compared between each patient's own AUC-E2
      and the corresponding E2 level on hCG day for the same patient. RESULTS: Although
      overall AUC-E2 correlated positively with E2 levels on hCG day, there was no
      consistent correlation between individual patients. CONCLUSIONS: AUC-E2 reflects
      more accurately the amount of E2 produced by the follicles during controlled
      ovarian hyperstimulation. The absence of a uniform correlation between AUC-E2 and
      E2 on hCG day may result in different conclusions when studying outcomes of IVF
      treatment.

PMID- 15844731
TI  - Single and repeated GnRH agonist stimulation tests compared with basal markers of
      ovarian reserve in the prediction of outcome in IVF.
AB  - PURPOSE: To study the value of a single or repeated GnRH agonist stimulation test
      (GAST) in predicting outcome in IVF compared to basal ovarian reserve tests.
      METHODS: A total of 57 women was included. In a cycle prior to the IVF treatment,
      on day 3, an antral follicle count (AFC) was performed and blood taken for basal
      FSH, inhibin B and E2 measurements, followed by a subcutaneous injection of 100
      microg triptorelin for the purpose of the GAST. Twenty-four hours later blood
      sampling was repeated. All the tests were repeated in a subsequent cycle. From
      the GAST E2 and inhibin B response were used as test parameters. The outcome
      measures were poor ovarian response and ongoing pregnancy. Group comparisons were
      done using the Mann-Whitney or chi-square test. Univariate and multivariate
      logistic regression was applied to assess which test revealed the highest
      predictive accuracy as expressed in the area under receiver-operating
      characteristic curve (ROC(AUC)). Clinical value was compared by calculating
      classical test characteristics for the best logistic models. RESULTS: All the
      basal and GAST variables were significantly different in the poor responders (n =
      19) compared to normal responders (n = 38). In the univariate analysis on cycle 1
      tests the AFC was the best predictor for poor ovarian response, while in cycle 2
      the E2 response in the GAST performed best (ROC(AUC) of 0.91 for both).
      Multivariate analysis of the basal variables led to the selection of AFC and
      inhibin B in cycle 1, yielding a ROC(AUC) of 0.96. Mean E2 response was selected
      in a multivariate analysis of the repeated GAST variables (ROC(AUC) 0.91). At a
      specificity level of -0.90, several logistic models including GAST variables
      appeared to have a sensitivity (-0.80), positive predictive value (-0.82) and
      false positive rate (-0.18), comparable to a logistic model containing AFC and
      inhibin B. None of the test variables showed a significant relation with ongoing
      pregnancy. CONCLUSIONS: The GAST has a rather good ability to predict poor
      response in IVF. However, comparing the predictive accuracy and clinical value of
      the GAST with a day 3 AFC and inhibin B, it appeared that neither a single nor a
      repeated GAST performed better. In addition, the predictive ability towards
      ongoing pregnancy is poor. Therefore, the use of the GAST as a predictor of
      outcome in IVF should not be advocated.

PMID- 15844732
TI  - Modified natural cycle using GnRH antagonist can be an optional treatment in poor
      responders undergoing IVF.
AB  - PURPOSE: To investigate the efficacy of gonadotrophin-releasing hormone (GnRH)
      antagonist supplementation during natural cycles in poor responders undergoing
      IVF-ET treatment. METHODS: We retrospectively evaluated 540 cycles of 433
      suitable patients who were divided by treatment protocol into modified natural,
      antagonist, and long agonist groups. There were 52 modified natural cycles with
      GnRH antagonist supplementation, 200 stimulated cycles with GnRH antagonist, and
      288 long GnRH agonist cycles. Cycle characteristics and treatment outcomes were
      compared between the groups. RESULTS: The mean number of oocytes retrieved in the
      modified natural group was significantly lower than in the stimulated antagonist
      and long agonist groups (1.4 +/- 0.5 vs. 2.3 +/- 1.1 and 2.5 +/- 1.1,
      respectively, p < 0.05). The respective implantation and pregnancy rates were 10%
      and 14.3%, 6.75% and 10.2%, and 7.4% and 10.6%. Cycle outcome and cycle
      properties were similar. CONCLUSIONS: Modified natural IVF cycle with GnRH
      antagonist supplementation is a feasible alternative to ovarian stimulation
      protocols in poor responders.

PMID- 15844733
TI  - A randomized, double-blind, multicenter study comparing a starting dose of 100 IU
      or 200 IU of recombinant follicle stimulating hormone (Puregon) in women
      undergoing controlled ovarian hyperstimulation for IVF treatment.
AB  - PURPOSE: To compare the efficiency and efficacy of two starting doses of
      recombinant FSH (follitropin-beta, Puregon) in women undergoing IVF treatment.
      METHODS: This prospective, randomized, double-blind, multicentric (N = 6) study
      included 192 women undergoing IVF using the long protocol of GnRH agonist who
      received either 100 IU or 200 IU of r-FSH per day. Gonadotropin dose adjustment
      was allowed after day 4 of stimulation. RESULTS: The average (SD) number of
      oocytes retrieved was 10.9 (5.4) and 12.2 (5.6) in the 100 IU and 200 IU group
      respectively (p = 0.067). The total doses of Puregon administered were 1887 IU
      and 2559 IU in the 100 IU and 200 IU group respectively. The number of
      transferable embryos, and the rates of pregnancies, cancelled cycles,
      miscarriages and adverse events including OHSS were comparable between the two
      groups. CONCLUSIONS: Women undergoing IVF have similar outcomes whether
      recombinant FSH is commenced in a dose of 100 IU or 200 IU for the first 4 days
      of stimulation.

PMID- 15844734
TI  - How long do parthenogenetically activated mouse oocytes maintain the ability to
      accept sperm nuclei as a genetic partner?
AB  - PURPOSE: Cytogenetic risk of intracytoplasmic sperm injection (ICSI) after
      artificial oocyte activation (post-activation ICSI) was evaluated in the mouse.
      METHODS: Mouse zygotes were produced by ICSI into eggs at various intervals after
      parthenogenetic exposure to strontium (Sr) for 30 min. Male pronucleus formation
      and the chromosome constitution were studied. RESULTS: Sperm nuclei injected into
      oocytes within 1 h after Sr exposure (from early through mid-telophase)
      transformed normally into male pronuclei, and the number of chromosome
      aberrations did not significantly increase in the resultant zygotes. When sperm
      nuclei were injected into eggs at intervals beyond 1 h after Sr exposure (from
      late telophase through the G1 pronuclear stage), the rate of male pronucleus
      formation was significantly reduced. The incidence of chromosome aberrations
      increased with time between oocyte activation and ICSI. CONCLUSIONS: ICSI into
      oocytes within 1 h after parthenogenetic activation produces cytogenetically
      competent embryos in the mouse.

PMID- 15844735
TI  - Blastocyst development after cryopreservation and subcutaneous transplantation of
      mouse ovarian tissue.
AB  - PURPOSE: To investigate follicle survival and developmental potential with IVF of
      cryopreserved, subcutaneously transplanted mouse ovarian tissue. METHODS: Fresh
      and frozen mouse ovarian tissue was autologously transplanted into subcutaneous
      tissue. Two weeks after the transplantation, the morphology and histology of the
      fresh and frozen grafts were compared. Superovulation and IVF was performed to
      evaluate the fertility potential of the frozen ovarian graft. RESULTS: Both fresh
      and frozen grafts of ovarian tissue survived in 14 of 16 mice (88%).
      Morphologically, both types of grafts resembled fresh ovarian tissue and
      contained follicles at all stages of folliculogenesis. A total of 73% of
      follicles in fresh grafts and 62% in frozen grafts survived after transplantation
      compared with fresh ovarian tissue. Sixteen ICR mice underwent superovulation. A
      total of 56 oocytes from antral follicles were recovered from the subcutaneously
      transplanted cryopreserved ovarian tissue. Fourteen (25%) oocytes were in
      metaphase II stage, 6 were fertilized by IVF, and 2 progressed to the blastocyst
      stage. CONCLUSIONS: Cryopreservation and subcutaneous transplantation of ovarian
      tissue provides a possible means of fertility preservation. The main loss of
      follicles occurred during grafting rather than during freezing and thawing.

PMID- 15844736
TI  - Evaluation of urine toxicology screens in an oocyte donor population.
AB  - PURPOSE: To assess the accuracy of drug self-reporting in oocyte donors. METHODS:
      Retrospective chart review of donors at Stanford University. RESULTS: 7% of the
      donor population had a significant positive urine toxicology screen. CONCLUSIONS:
      Donors may not fully disclose details of drug use, so urine toxicology screening
      should be considered in this patient population.

PMID- 15844737
TI  - Histological evaluation of the effects of cryopreservation in bovine ovarian
      tissue.
AB  - The aim of this study was to show the effects of freezing and thawing in bovine
      ovarian tissue by histological analysis. Ten cortical slices (2-4 mm in diameter)
      were obtained from each ovary by tru-cut biopsy and randomly divided into two
      groups: five fragments were immediately processed as a fresh tissue control
      group, while the remaining 5 fragments were slowly frozen using DMSO plus sucrose
      as cryoprotectors, then stored for two weeks and quickly thawed. Histological
      examination of all cryopreserved ovarian fragments showed no damage in the
      structure of the organ. Furthermore, there was no difference in the average
      number of primordial and primary follicles between the two groups of ovarian
      tissue. These data suggest that the bovine ovary can be used as a suitable model
      to test new freezing and thawing procedures in search for a standard protocol of
      human ovary cryopreservation.

PMID- 15844738
TI  - Clear speech.

PMID- 15844739
TI  - Five-year changes in middle ear function for older adults.
AB  - Longitudinal changes in tympanometric measures of middle ear function over five
      years were reported for a large population of older adults. Findings were similar
      for men and women, for right and left ears, and across age groups from 48 to 92
      years. Although some of the mean changes reached statistical significance, the
      vast majority of observed changes were small in magnitude relative to the
      observed variability and the tolerances of the measuring instrument. Observed
      mean changes in Peak Ytm for older adults were quite small and were in the
      positive direction. This is counter to changes that would be predicted on the
      basis of increases in the stiffness of the middle ear transmission system with
      advancing age suggested in earlier reports. Overall, the findings suggest little
      in the way of functional change in middle ear mechanics over a span of five years
      in older adults.

PMID- 15844740
TI  - Estimating audiometric thresholds using auditory steady-state responses.
AB  - Human auditory steady-state responses (ASSRs) were recorded using stimulus rates
      of 78-95 Hz in normal young subjects, in elderly subjects with relatively normal
      hearing, and in elderly subjects with sensorineural hearing impairment. Amplitude
      intensity functions calculated relative to actual sensory thresholds (sensation
      level or SL) showed that amplitudes increased as stimulus intensity increased. In
      the hearing-impaired subjects this increase was more rapid at intensities just
      above threshold ("electrophysiological recruitment") than at higher intensities
      where the increase was similar to that seen in normal subjects. The thresholds in
      dB SL for recognizing an ASSR and the intersubject variability of these
      thresholds decreased with increasing recording time and were lower in the hearing
      impaired compared to the normal subjects. After 9.8 minutes of recording, the
      average ASSR thresholds (and standard deviations) were 12.6 +/- 8.7 in the normal
      subjects, 12.4 +/- 11.9 dB in the normal elderly, and 3.6 +/- 13.5 dB SL in the
      hearing-impaired subjects.

PMID- 15844741
TI  - Clear speech for adults with a hearing loss: does intervention with communication
      partners make a difference?
AB  - Spouses of persons with hearing loss served as talkers to examine the benefits of
      clear speech intervention. One talker received intervention on clear speech. A
      second talker was simply instructed to speak clearly. Each talker was recorded
      reading sentences in three conditions: conversational speech, clear speech one
      week postintervention, and clear speech one month postintervention. Speech
      acoustic measures were obtained. Then the sentences were presented to subjects
      with normal hearing and subjects with hearing loss to measure speech recognition.
      Results showed that simply asking a talker to speak clearly was effective in
      eliciting clear speech; however, providing intervention yielded changes in more
      speech parameters, more stable changes, and better speech recognition. When
      listening to the talker who received intervention, subjects with hearing loss
      achieved the same performance as subjects with normal hearing. However, they
      performed worse than subjects with normal hearing when listening to the talker
      who received clear speech instructions only. Individuals with hearing loss would
      receive speech recognition benefits if their partners were provided with clear
      speech intervention.

PMID- 15844742
TI  - Multiple auditory steady-state responses to bone-conduction stimuli in adults
      with normal hearing.
AB  - ASSR thresholds to bone-conduction stimuli were determined in 10 adults with
      normal hearing using mastoid placement of the bone oscillator. ASSRs to 0-50 dB
      HL bone-conduction stimuli and to 30-60 dB HL air-conduction stimuli were
      compared. The effect of alternating stimulus polarity on air- and bone-conduction
      ASSRs was also investigated. Stimuli were bone- and air-conduction amplitude
      modulated tones (500-4000 Hz carrier frequencies, modulated at 77-101 Hz). ASSRs
      were recorded using the Rotman MASTER research system. Mean (1SD) bone-conduction
      ASSR thresholds were 22(11), 26(13), 18(8), and 18(11) dB HL for 500, 1000, 2000,
      and 4000 Hz, respectively. Except for a steeper slope at 500 Hz, ASSR intensity
      amplitude functions for binaural bone- and air-conduction stimuli showed the same
      slopes; intensity-phase-delay functions were steeper at 1000 Hz for ASSRs to bone
      conduction stimuli. ASSR amplitudes and phases did not differ for single- versus
      alternated-stimulus polarities for both bone- and air-conduction stimuli. The
      steeper amplitude slope for ASSRs to 500 Hz stimuli may reflect a nonauditory
      contribution to the ASSR.

PMID- 15844743
TI  - Human frequency-following responses to binaural masking level difference stimuli.
AB  - Binaural masking level difference is the behavioral threshold difference between
      a diotic condition (SoNo) and a dichotic condition with a 180 degrees interaural
      phase delay of either the signal (SpiNo) or the masker (SoNpi). Threshold
      disparity is partially related to coincidence-detecting units in the medial
      superior olive that are sensitive to low-frequency binaural stimuli with
      interaural phase differences. Previous surface evoked potential studies report
      significant latency and amplitude differences to SpiNo stimuli with respect to
      SoNo stimuli in the P1-N1 auditory event related potential, but no study has
      reported physiologic masking level differences in a brain stem evoked potential.
      The human frequency-following response (FFR) represents activity from low
      frequency, phase locking neural units in the upper brainstem. Unmasked FFRs to
      500 Hz tone bursts and masked FFRs using a 1.5 kHz low-pass masker were recorded
      from nine normal-hearing adult subjects. Significant reduction in FFR amplitude
      occurred in the SoNo condition, re the So condition, with masker intensities near
      the psychoacoustic SoNo masking level. Significant FFR amplitude recovery was
      observed for both the SoNpi and SpiNo conditions. These results support the role
      of phase-locked neural activity in brainstem mechanisms involved in perceptual
      masking release.

PMID- 15844744
TI  - Factors predicting severity of tinnitus: a population-based assessment.

PMID- 15844745
TI  - Group therapist countertransference to trauma and traumatogenic situations.
AB  - In this introduction to the special issue on "Group Therapist Countertransference
      to Trauma and Traumatogenic Situations," the author notes that for many
      therapists it is not only group member disclosures and re-enactments, but also
      the co-occurring, sociopolitical contexts in which they live that may involve
      traumatic challenges. He considers three historically evolving views of
      countertransference: (1) the "classical"position, (2) the "totalistic" view, and
      (3) the "intersubjective/relational" view. He views the therapist's intense
      emotionality (as opposed to clinical detachment) in response to trauma as
      inevitable, and considers the particular roles of "bystander," "perpetrator," and
      "victim" induced in the therapist by traumatic re-enactments in the group. He
      concludes with a synopsis of some of the key points made in each of the
      contributions to the special issue.

PMID- 15844746
TI  - In the belly of the beast: traumatic countertransference.
AB  - The authors discuss their work together in a consultation process. One author led
      many groups that were created to facilitate recovery for persons directly
      impacted by the terrorist attacks on September 11, 2001; the other acted as
      consultant to the therapist/leader. The leader was a resident of New York City at
      the time of the attacks; the consultant lived in a distant Midwestern city and
      the two had never met prior to the work. They describe their experience of
      working together and the role of this collaboration in the lives of the leader
      and the groups. Well aware that little exists in the literature about groups led
      by leaders having experienced the same trauma as group members, the authors pay
      special attention to the countertransference that each underwent and raise
      questions about the effects of that on the group process.

PMID- 15844747
TI  - The effect of trauma on the conductor of the group: a type of identificatory
      countertransference.
AB  - Trauma affects the conductor of the group as well as the group members. This
      identificatory countertransference of the group conductor is a resultant of the
      coming together of the conductor's internal and external worlds, the interplay of
      introjections, projections, and empathy. It is inconceivable that a conductor of
      a group can project a "blank screen " of technical neutrality when trauma
      impinges upon everyone. From a psychodynamic perspective, this article explores
      groups under the throes of trauma, the interplay of that trauma with the
      conductor's feelings, and the effects on his or her role in the group. The
      article also explores the effect of trauma upon the affective process within the
      group and upon the cognitive processes of the conductor and group members.

PMID- 15844748
TI  - Management of intense countertransference in group psychotherapy conducted in
      situations of civic conflict.
AB  - Conducting group psychotherapy in a situation of intractable conflict such as
      Northern Ireland activates turbulent emotional dilemmas within psychotherapists
      and group members alike. Professional practice and therapeutic zeal must struggle
      daily to survive the stark encounter with the reality of a regressive and
      primitive psychology and on occasion may succumb to atavistic tendencies,
      dragging relationships down to primitive levels and leaving connections broken.
      In this article, three group therapists describe their countertransference
      struggles when leading such groups. They meet in a psychosocial setting in which
      the risk to one's psyche parallels the risk to one's life and limb. The
      countertransference experienced here is dark, indeed identified by one author as
      not unlike Dante's Inferno. They describe how understanding their personal
      countertransference enables them to survive emotionally even though it may not
      always lead to the survival of their groups. The effect of those struggles also
      troubled the act of writing itself making cooperation difficult on occasion, a
      mirror of the external social matrix.

PMID- 15844749
TI  - Countertransference in the context of the fourth basic assumption in the
      unconscious life of groups.
AB  - The treatment of choice for traumatized and difficult patients is psychoanalysis
      or psychoanalytical therapy followed by intensive group analysis for an unlimited
      period of time. The group is able to help the analyst make therapeutic use of
      inevitable difficulties in countertransference processes. Also, traumatized and
      difficult patients are likely to create the basic assumption of Incohesion:
      Aggregation/Massification, and to personify the roles associated with it. These
      processes can be used in order to provide such patients with appropriate
      therapeutic attention involving both containment and holding, and interpretation.
      Extensive clinical data from psychoanalysis and group analysis are used to
      illustrate both this clinical approach and the author's theory of Incohesion.

PMID- 15844750
TI  - Relational perspectives regarding countertransference in group and trauma.
AB  - A relational/constructivist view incorporates contemporary trends toward viewing
      countertransference and co-transference as results of mutual intersubjective
      influence. It moves toward a view of the socially constructed nature of human
      reality, toward recognizing the therapist's as well as the members' irreducible
      individuality and initiative taking; and toward therapy as about meaning-making
      rather than scientific discovery of The Truth. General clinical examples, and
      examples of working specifically with trauma, are given.

PMID- 15844751
TI  - Holding hope and humanity in the face of trauma's legacy: the daunting challenge
      for group therapists.

PMID- 15844752
TI  - Countertransference: the evolution of a construct.

PMID- 15844753
TI  - Memantine: targeting glutamate excitotoxicity in Alzheimer's disease and other
      dementias.
AB  - The management of dementia has changed since the development of new antidementia
      drugs. The benefits observed in Alzheimer's disease (AD) with selective
      cholinergic transmission treatments are mainly symptomatic, without clear
      evidence of neuroprotection. The hypothesis that glutamate-mediated neurotoxicity
      is involved in the pathogenesis of AD is finding increasingly more acceptance in
      the scientific community. Glutamate receptors are overactive, and N-methyl-D
      aspartate (NMDA) receptor antagonists have therapeutic potential for the
      treatment of AD and other neurological disorders. Memantine is a noncompetitive
      NMDA antagonist that is considered a neuroprotective drug. Memantine's capacity
      has been demonstrated in preclinical studies, and it is considered a useful
      symptomatic treatment for AD. Memantine has been shown to benefit cognition,
      function, and global outcome in patients with moderate to severe AD, and it is
      currently approved by the US Food and Drug Administration (FDA) for the treatment
      of moderate to severe AD. Recently, memantine has also demonstrated efficacy in
      the initial stages of AD, although FDA authorization is pending. This review
      highlights the important pharmacological and clinical aspects of memantine, as
      well as some basic mechanisms mediating glutamatergic neurodegeneration.

PMID- 15844754
TI  - Sleep-wake states in transgenic mouse models overexpressing the human beta
      amyloid precursor protein.
AB  - Studies testing the amyloid hypothesis and recent advances in mouse molecular
      genetic technologies have played a critical role in improving our understanding
      of Alzheimer's disease (AD). Mouse models of AD currently available show only
      some of the characteristic neuropathology in human AD. Studies have demonstrated,
      however, that these models are excellent tools for characterizing different
      aspects of the molecular pathology of AD and the neurobiological basis for the
      clinical heterogeneity in AD. The present discussion focuses on behavioral and
      physiological data obtained in transgenic (Tg) mice overexpressing the mutant
      human beta-amyloid precursor protein (hbetaAPP). This mouse model exhibits memory
      and neurophysiological deficits at ages preceding amyloid-beta-peptide (Abeta)
      plaque formation that worsened with age and Abeta plaque formation. In spite of
      these findings, very little emphasis has been placed on characterizing the
      neurobiological basis of the diverse neuropsychiatric symptoms that are also
      observed in AD, including sleep disturbances. Taking into consideration the
      relationship between memory processes and sleep, the use of animal models of AD
      as a preclinical bioassay has the potential to characterize the neural substrates
      mediating clinical manifestations of AD, such as sleep-wake states, and
      contribute to the development of treatments for early stages of AD.

PMID- 15844755
TI  - Cholesterol and apolipoprotein E in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in North America
      and Europe. The incidence of the disease rises dramatically with age. AD is a
      complex multifactorial disorder that involves numerous susceptibility genes, but
      the exact pathogenesis and biochemical basis of AD is not well understood
      Cholesterol is receiving a great deal of attention as a potentially crucial
      factor in the etiology of AD. Almost all cholesterol in the brain is synthesized
      in the brain. Cholesterol exits the brain through the blood-brain barrier (BBB)
      in the form of apolipoprotein E (ApoE) or by first being converted to a more
      polar compound, 24(S)-hydroxycholesterol, which is elevated in individuals with
      AD. The key event leading to AD appears to be the formation and aggregation in
      the brain of amyloid beta (Abeta) peptide, a proteolytically derived product of
      amyloid precursor protein (APP). Cholesterol has been demonstrated to modulate
      processing of APP to Abeta. High levels of cholesterol are associated with
      increased risk of AD. Patients taking cholesterol-lowering statins have a lower
      prevalence of AD. ApoE, which transports cholesterol throughout the brain,
      exhibits an isoform-specific association with AD such that the E4 isoform, by
      unknown mechanisms, shifts the onset curve toward an earlier age.

PMID- 15844756
TI  - Focused supervision of high-risk fall dementia patients: a simple method to
      reduce fall incidence and severity.
AB  - Dementia units in nursing homes have a disproportionately high number of
      demographic risk factors for falls. Many residents have a previous history of
      falls, the inability to call for assistance, and the inability to remember safety
      instructions. For interdisciplinary falls review committees, this population may
      be the most difficult to manage. The Virginia Veterans Care Center (VVCC)
      Dementia Unit Interdisciplinary Fall Team instituted a novel practice for
      reducing the number and severity of falls among the highest risk group of
      dementia patients. Certified nursing assistants (CNAs) were assigned to high-risk
      residents for focused supervision. The patients received consistent supervision
      by selected CNAs during the day and evening shifts. Eight residents identified as
      high risk who continued to have falls despite multiple interventions were
      selected for the study. A comparison of four months of intervention with the four
      months prior to the intervention revealed a significant (p = 0. 024) fall
      reduction during the intervention months. Individually, seven of the eight
      participants had reduced falls during the intervention period. A 5-point scale
      for fall severity demonstrated an overall reduction in fall severity during that
      period. Individually, five of the eight patients had a decreased fall severity,
      and one had no change. Two patients experienced an increase in fall severity due
      to ongoing medical problems. While the small number of patients in the study
      limits the power of the results, this novel intervention of using designated CNAs
      to supervise high-risk fall residents with dementia may prove helpful for staff
      in other nursing facilities.

PMID- 15844757
TI  - Activity situations on an Alzheimer's disease special care unit and resident
      environmental interactions, time use, and affect.
AB  - Routine activity situations on an Alzheimer's disease (AD) special care unit were
      examined with respect to residents' social and physical environmental
      interactions, time use, and apparent affect. Using a computer-assisted
      observational tool, observers recorded prevailing activity situations and
      corresponding behaviors and affects of seven residents every 10 minutes, from
      8:00 AM to 8:00 PM, across four days. Although meals/snacks and some activity
      groups were positively associated with use of physical objects and engagement in
      activities, residents were predominantly environmentally disengaged, inactive, or
      without positive affects during the most prevalent activity situations of
      background media, downtime, and television. Findings suggest that routine
      activity situations may act as potent environmental influences on the quality of
      life (QOL) of people with AD and mediate the effectiveness of other environmental
      interventions undertaken on their behalf.

PMID- 15844758
TI  - Knowledge of personal information and caregiver awareness in Alzheimer's disease.
AB  - We assessed the ability of 73 patients with Alzheimer's disease (AD) to recall
      important personal information like their names, their caregivers 'names, their
      addresses, and their telephone numbers. We also assessed their caregivers'
      awareness of their abilities. There was an association between the abilities of
      the patients and their Mini-Mental Status Examination (MMSE) scores, with the
      patients with the lowest MMSE scores making the most errors. Five to 10 percent
      of the mildest patients were unable to state their addresses and telephone
      numbers correctly. The caregivers of the patients with intermediate MMSE scores
      made the most errors in their predictions, with up to 50 percent being incorrect
      and up to 37 percent overestimating their patients' abilities. We concluded that
      AD patients lose their ability to provide personal information as their illness
      progresses. Caregivers of patients with MMSE ranging from 10 to 25 are the most
      likely to be unaware of their patients' impairment. These findings highlight
      safety concerns in AD.

PMID- 15844759
TI  - Gender influences as an impediment to knowledge sharing: when men and women fail
      to seek peer feedback.
AB  - Little research has considered how work team characteristics influence feedback
      seeking behavior among team members. The authors' aim in this research was to
      identify central sources of influence on feedback-seeking behavior in a mixed
      gender context. They placed men and women in work groups of varying gender
      composition. The participants then participated in a gender-biased (perceived as
      either male-oriented or female-oriented) negotiation exercise. Findings indicated
      that the gender of the participant, the team's gender composition, and the gender
      orientation of the task influenced feedback-seeking behavior among team members.

PMID- 15844760
TI  - Accountability and need for cognition effects on contrast, halo, and accuracy in
      performance ratings.
AB  - In the present study, the authors investigated the effects of accountability and
      need for cognition on contrast errors, halo, and accuracy of performance ratings
      examined in good and poor performance context conditions, as well as in a context
      free control condition. The accountability manipulation reduced the contrast
      effect and also modified rater recall of good ratee behavior. Accountability
      reduced halo in ratings and increased rating accuracy in a poor performance
      context. Accountability also interacted with need for cognition in predicting
      individual rater halo.

PMID- 15844761
TI  - Dispositional and task-specific social-cognitive determinants of physical effort
      perseverance.
AB  - The authors performed 3 studies to investigate the effects of social-cognitive
      variables on physical effort perseverance. Linear hierarchical regressions
      indicated that task-specific variables and perceived ability or competence
      accounted for the majority of perseverance variance in all 3 studies. The
      strongest single predictors in this cluster of variables were perceived
      competence, confidence, and readiness to invest effort. Physical self-health and
      ability accounted for a lesser portion of effort perseverance variance, with self
      presentation confidence being the major single predictor in this cluster. The
      goal orientation cluster accounted for the least amount of effort perseverance
      variance. Together with task-specific confidence and the readiness to invest
      effort, as well as determination and commitment and competence, the findings
      support the contention that task-specific efficacious beliefs to a large extent
      determine persistence and endurance behaviors.

PMID- 15844762
TI  - Southeast Asian immigrants' perceptions of good adolescents and good parents.
AB  - The authors examined the extent to which Southeast Asian immigrant parents and
      adolescents agree on what it means to be a "good" parent and a "good" adolescent.
      Thirty-six parents and 37 adolescents of Cambodian, Hmong, Lao, and Vietnamese
      descent participated in a series of focus groups. Content analyses of their
      discussions showed that good adolescents were obedient, helpful around the house,
      and respectful to parents and elders, and good parents were those who provide
      for, nurture, and monitor children's activities. The findings suggest that ideas
      about good parents and good adolescents are influenced by both the parents'
      traditions and by adolescents' acculturation to American values.

PMID- 15844763
TI  - Event-related potentials related to normal and morphed emotional faces.
AB  - S. Bentin and L. Y. Deouell (2000) have suggested that face recognition is
      achieved through a special-purpose neural mechanism, and its existence can be
      identified by a specific event-related potential (ERP) correlate, the N170
      effect. In the present study, the authors explored the structural significance of
      N170 by comparing normal vs. morphed stimuli. They used a morphing procedure that
      allows a fine modification of some perceptual details (first-order relations).
      The authors also aimed to verify the independence of face identification from
      other cognitive mechanisms, such as comprehension of emotional facial
      expressions, by applying an emotion-by-emotion analysis to examine the emotional
      effect on N170 ERP variation. They analyzed the peak amplitude and latency
      variables in the temporal window of 120-180 ms. The ERP correlate showed a
      classic N170 ERP effect, more negative and more posteriorly distributed for
      morphed faces compared with normal faces. In addition, they found a
      lateralization effect, with a greater right-side distribution of the N170, but
      not directly correlated to the morphed or normal conditions. Two cognitive codes,
      structural and expression, are discussed, and the results are compared with the
      multilevel model proposed by V. Bruce and A. W. Young (1986, 1998).

PMID- 15844764
TI  - [Recent views on the pathogenesis of cardiovascular damage associated with
      rheumatoid arthritis].
AB  - Cardiovascular disease is the commonest cause of premature mortality in
      rheumatoid arthritis and several data have shown that rheumatoid arthritis is an
      independent risk factor for the development of atherosclerotic disease. In last
      years it has become evident that atherosclerosis is an immune-mediated
      inflammatory disorder sharing a number of pathogenic features with rheumatoid
      arthritis. It is conceivable, therefore, that chronically raised concentrations
      of proinflammatory cytokines and pathological immune response characterizing
      rheumatoid arthritis may play a key role in inducing acceleration of
      atherosclerotic processes and, consequently, in the development of cardiovascular
      disease in these patients.

PMID- 15844765
TI  - [A model for epidemiological study in general practice: mortality. Study of
      cohort in Pavia].
AB  - For defining the health state of the population and demonstrating that computed
      general practice can be a preferential observation point for epidemiological
      study, we analyzed, as general practitioners, database of a dynamic cohort of
      1501 subjects (m:724, f:777) living in Pavia and monitored from 1/1/1992 to
      12/31/2001. In this paper we present mortality data compared to Italy in 1994.
      During the period, 209 deaths occurred (m:107, f:102). Differently from Italy, in
      Pavia cancer was the first cause of death in both sexes. When cardiovascular
      fatal events were analysed, age of death occurred 8.7 years in advance in males,
      while age of death for cancer was similar in both sexes. Sudden death represented
      one quarter of cardiovascular deaths. General practitioners' database can be an
      important and useful epidemiological source to detect areas with different risks
      of illness. Furthermore database offers the possibility to determine mortality
      rate for illness like sudden death not included in national statistical studies.

PMID- 15844766
TI  - [Role of S-100B for evaluation of traumatic brain injury in patients with alcohol
      intoxication].
AB  - The neuroprotein S-100B was identified as a possible marker for primary brain
      damage. The objective of this prospective study was to determine the diagnostic
      validity of plasma measurements of S-100B in patients with minor head injury and
      acute alcohol intoxication. The results of S-100B plasma levels were compared to
      the Glasgow-Coma-Scale score, the neurological examination and the CCT data.
      Median S-100B levels of the CCT+ patients were significantly increased compared
      to those of the CCT- patients without being influenced by alcohol. Increased S
      100B plasma levels seem to indicate a primary brain damage.

PMID- 15844767
TI  - [Prognostic value of serum beta2-microglobulin in multiple myeloma].
AB  - We have analysed a series of 96 patients with multiple myeloma (MM) to the
      purpose to verify the prognostic meaning of the beta2-microglobulin (B2M) and the
      validity of the staging systems proposed by Bataille and Jacobson who use the B2M
      respectively associated to the serum C-reactive protein (CRP) and to the serum
      albumin. In our series of patients the serum level of B2M at the diagnosis was
      directly correlated with the myelomatous cellular mass. We have found besides an
      inverse correlation between B2M and survival. Also the serum level of CRP was
      inversely correlated with the survival, while a direct correlation was found
      between the serum albumin and the survival: ipoalbuminemia was confirmed as a
      predictive index of short survival. Staging our patients with MM according to the
      proposal of Bataille, we identified also in our series three prognostic groups
      with different median survival: respectively 72, 40 and 18 months. Applying
      finally the staging proposal of Jacobson to our series, four stages were
      individualized, with median survival respectively of 70, 52, 26 and 10 months. We
      confirm the prognostic value of the B2M in MM.

PMID- 15844768
TI  - [Pulmonary hypertension during lupus erythematosus].
AB  - A patient with pulmonary hypertension (PH) during subacute cutaneous lupus
      erythematosus is described. Since the PH is characteristic of other connective
      tissue diseases (systemic sclerosis, Sharp syndrome), if a systemic lupus
      erythemtosus is coexistent, one should make a careful diagnostic screening
      (capillaroscopy, anti-centromere, or anti-Sc170, or anti-RNP antibodies) to show
      a possible overlap-syndrome.

PMID- 15844769
TI  - [Posturology. Methodological problems and scientific evidence].
AB  - In the last years, the word "posturology" has been used in complementary medicine
      to define the discipline studying the relation between posture and many
      pathologies, above all chronic pain. Posturology is more and more frequently
      recommended as a diagnostic-therapeutic system for treatment of chronic
      complaints, on the base of which different health caregivers (physicians and not)
      treat the same clinical problem, with very different methodological patterns and
      therapies. If it is true that many scientific papers highlight a relation between
      body posture and muscoloskeletal disorders; nevertheless on the base of
      scientific literature, it is not possible to demonstrate any scientific principle
      showing that the correction of small alterations of posture on the base of a
      stabilometric analysis can improve muscoloskeletal pain or other diseases.
      Rather, it is true the opposite. Today a positive stabilometric test can be
      referred only to an alteration of the vestibulo-spinal system.

PMID- 15844770
TI  - [Experimenting in Italy: from GISSI to the Ministerial Decree].

PMID- 15844771
TI  - [Inherited thrombophilia].
AB  - Inherited thrombophilia can be defined as a genetically determined predisposition
      to develop thromboembolic complications. Inherited prothrombotic risk factors
      include antithrombin deficiency, protein C and protein S deficiencies, activated
      protein C resistance due to Leiden factor V mutation, inherited
      hyperhomocysteinemia, prothrombin G20210A variant, dysfibrinogenemia and elevated
      factor VIII levels. In this review we briefly analyze, from an epidemiologic,
      clinic and diagnostic point of view, the main inherited prothrombotic risk
      factors. Finally, we discuss the synergism between genetic and acquired
      prothrombotic risk factors in some conditions such as pregnancy and
      cardiovascular diseases.

PMID- 15844772
TI  - [Alcohol consumption and circulating markers of inflammation].
AB  - Atherosclerosis, the leading cause of death in western countries, is a
      multifactiorial condition in which a local and low-grade inflammatory response
      plays an important role. Elevation in markers of inflammation prospectively
      defines risk of atherosclerotic complications and predicts all-cause mortality.
      Alcohol consumption has been related with all-cause mortality and cardiovascular
      risk with a J-shaped relationship, suggesting that alcohol consumption might have
      an antiinflammatory effect. This review assesses the current state of knowledge
      regarding the immunomodulatory effect of moderate alcohol consumption.

PMID- 15844773
TI  - De novo deletion 7q36 resulting from a distal 7q/8q translocation: phenotypic
      expression and comparison to the literature.
AB  - We report on a 6-year-old male patient with de novo 7q36 deletion and 8q24.3
      duplication diagnosed by combining traditional G-banding and FISH studies. His
      clinical history was remarkable for pre- and postnatal growth retardation,
      neonatal feeding problems and developmental/mental retardation with non-verbal
      communication. He presented microcephaly, large ears, narrow palpebral fissures
      with blepharoptosis, epicanthic folds, large depressed nasal bridge, bulbous
      nasal tip, right cryptorchidism and delayed bone age on X-rays. There was no
      evidence of holoprosencephaly (HPE) or sacral agenesis sequence. By using in FISH
      analysis a series of YACs linearly ordered along the 7q36 region, the precise
      breakpoint on 7q36 was found to be within the target region of the YAC 742G8, a
      YAC that appeared to be only partially deleted. Clinical and chromosomal findings
      in this patient are compared to those previously recorded in similarly
      investigated patients from the literature with terminal 7q deletion.

PMID- 15844774
TI  - A natural history of a child with monosomy 5p syndrome (Cat-cry/Cri-du-chat
      syndrome) during the 18 years of follow-up.
AB  - A record of a natural history of a long-term case study devoted to monosomy 5p
      (Cat-cry/Cri-du-chat) syndrome has been described rarely. Knowledge on the range
      of the changes in phenotype attributable to advancing age can be useful in
      clinical diagnosis of monosomy 5p at the different developmental stages,
      including adolescence, as well in prognosis for genetic counseling. In this case
      a detailed analysis of the morphologic phenotype in a girl with del(5)(p13.3)
      observed from 4 months to 18 years of age is reported. The comparative analysis
      of the girl's phenotype in different developmental stages has revealed that
      microcephaly, flat occipital region, face asymmetry, wide spaced palpebral
      fissures, epicanthic folds, small mouth fissure, thin mucous lip, small and low
      set ears and short IV metacarpals has not changed with advancing age. However,
      facial asymmetry was more evident, frontal tubers were less prominent, nasal root
      and back became prominent nasal back became elongated, the subnasal region was
      shorter and marked malocclusion appeared.

PMID- 15844775
TI  - A de novo t (X;8)(p11.2;q24.3) demonstrating Cornelia de Lange syndrome
      phenotype.
AB  - Cornelia de Lange syndrome is a rare syndrome of hitherto unknown etiology. We
      present a 9-months old female patient with de novo t (X;8) (p11.2;q24.3) and
      Cornelia de Lange Syndrome phenotype. De novo t (X;8)(p11.2;q24.3) was not
      reported so far in Cornelia de Lange syndrome.

PMID- 15844776
TI  - Physical and developmental phenotype analyses in a boy with Wolf-Hirschhorn
      syndrome.
AB  - Wolf-Hirschhorn syndrome (WHS) is a rare genetic condition with characteristic
      facial traits, organ malformations, functional impairment and developmental delay
      due to partial short arm monosomy of chromosome 4. Although several hundreds of
      cases have been published to date, a systematic collection of its clinical
      symptoms and anthropological traits is missing in the literature, and reports on
      abilities and needs of children with WHS are scanty. Results of detailed physical
      and developmental phenotype analyses in a 1 10/12-year-old boy with monosomy
      4p15.2-pter are presented. Physical analyses were based on systematic data
      acquisition. They disclosed a total of 32 clinical symptoms and 46
      anthropological traits. Developmental analyses were based on the child's
      interactive play in an environment structured according to Montessori principles.
      They disclosed a total of 44 abilities and a number of needs to be satisfied by
      the environment for the support of the child's psychic and intellectual growth.
      While the physical phenotype is important for the diagnostic process, the
      developmental phenotype is essential for parental counseling.

PMID- 15844777
TI  - A child with Beckwith-Wiedemann syndrome and posterior urethral valves.
AB  - Beckwith-Wiedemann syndrome is a somatic overgrowth syndrome characterized by a
      variable incidence of congenital anomalies, including hemihypertrophy,
      omphalocele, macroglossia and renal malformations. We report a child with
      Beckwith-Wiedemann syndrome and posterior urethral valves. Urethral valve
      resection was successfully performed under general anesthesia after voiding
      cystourethrography. This is the first report of Beckwith-Wiedemann syndrome
      associated with posterior urethral valves.

PMID- 15844778
TI  - Two extra euchromatic bands in the qh region of chromosome 9.
AB  - Chromosome analysis in a fetus revealed an abnormal appearance of chromosome 9.
      The secondary constriction region of chromosome 9 was very large and two separate
      G+ bands were observed within this region with GTG banding. Parents' karyotypes
      showed maternal inheritance of this variant chromosome 9. Two G+ bands were
      stained negative with C banding both in the fetus and in the mother. The mother
      was phenotypically normal. Regarding phenotypically normal mother, normal fetal
      ultrasonographic findings and the similar cases described before in the
      literature it was considered that the fetus would be normal. Physical examination
      of the baby was normal after birth as expected. The existence of two G+ bands in
      9qh was considered to be a normal variant in humans.

PMID- 15844779
TI  - A comparison of maternal age, sex ratio and associated anomalies among
      numerically aneuploid, structurally aneuploid and euploid holoprosencephaly.
AB  - During the period January 1987-July 2003, 59 cases of perinatally detected
      holoprosencephaly (HPE) with cytogenetic results were identified among 97,306
      deliveries at Mackay Memorial Hospital. Among these 59 cases with HPE, 25 had
      euploidy, 27 had numerical aneuploidy, and 7 had structural aneuploidy. In the
      euploid cases, the male:female sex ratio was 0.39:1, whereas in the aneuploid
      cases, the ratio was 1:1. The mean (+/-SD) maternal ages for numerical
      aneuploidy, structural aneuploidy, and euploidy were 33.0 +/- 5.1 years, 27.9 +/-
      2.1 years, and 27.8 +/- 5.0 years, respectively. The frequencies of associated
      major structural anomalies other than craniofacial defects in the cases with
      numerical aneuploidy, structural aneuploidy, and euploidy were 85.7%, 0%, and
      16%, respectively. The present study of HPE suggests that a female excess appears
      only in the euploid cases, and advanced maternal age and structural anomalies are
      more commonly associated with the numerically aneuploid cases than the
      structurally aneuploid and euploid cases.

PMID- 15844780
TI  - Distal trisomy 10q/partial monosomy 14q: an unusual clinical picture.
AB  - A case of twin boy with partial trisomy for the distal part of the long arm of
      chromosome 10 (10q24-->qter) and a concomitant monosomy 14(q32-->qter) is
      reported. The chromosomal abnormalities resulted from a paternal balanced
      translocation involving chromosomes 10 and 14. An additional clinical feature was
      observed, viz. hypoplastic lungs. The proband's phenotype was compared to
      previously reported patients with partial trisomy 10q or 14q deletion.

PMID- 15844781
TI  - "Ring syndrome" involving chromosome 2 confirmed by FISH analysis using
      chromosome-specific subtelomeric probes.
AB  - "Ring syndrome" is described as those cases with complete ring chromosomes
      showing, independently of the chromosome involved, severe growth failure, minor
      dysmorphic features, and mild-to-moderate mental retardation, without major
      malformations. We present a girl with ring 2 chromosome, exhibiting severe growth
      failure, minor dysmorphic features, spontaneously closed ventricular septum
      defect, and normal development. G-banding chromosome analysis and fluorescence in
      situ hybridization (FISH) analysis using chromosome-specific subtelomeric probes
      (2ptel, 2qtel) demonstrated the major karyotype as 46,XX,r(2)(p25.3q37.3).ish
      r(2)(2ptel+,2qtel+). We review the cases with "ring syndrome" confirmed by FISH
      using chromosome-specific subtelomeric probes, suggesting that this method might
      be useful to predict developmental prognosis in a case with an apparently
      complete ring chromosome.

PMID- 15844782
TI  - A whistling face syndrome case with bilateral skin dimples.
AB  - The whistling face syndrome (Freeman-Sheldon Syndrome) is a rare disorder
      characterized by typical face and limb abnormalities. A wide range of clinical
      findings have been reported. We report unusual skin dimples in a sporadic case
      with the whistling face syndrome.

PMID- 15844783
TI  - Unusual pattern of inheritance and orodental changes in the Ellis-van Creveld
      syndrome.
AB  - Ellis-van Creveld (EVC) syndrome (chondroectodermal dysplasia, mesoectodermal
      dysplasia, OMIM 225500) is an autosomal recessive skeletal dysplasia
      characterized by short limbs, short ribs, postaxial polydactyly and dysplastic
      nails and teeth. Oral manifestations tend to be pathognomonic such as multiple
      broad labial frenula and congenital missing teeth. In this study we report three
      Egyptian families with six cases of EVC syndrome. An unusual pattern of
      inheritance with father to son or to daughter transmission was observed in 2
      consanguineous families thus demonstrating pseudo-dominant inheritance, probably
      for the first time in the literature. A new consistent orodental anomaly found in
      all our cases was bifid tip of the tongue. We emphasize study of orodental
      anomalies in future cases for accurate diagnosis of Ellis-van Creveld syndrome
      and its probable differential diagnosis from Weyers acrodental dysostosis.

PMID- 15844784
TI  - X-linked reticulate pigmentary layer. Report of a new patient and demonstration
      of a skewed X-inactivation.
AB  - We report a boy, born to healthy first cousin parents, with diffuse
      hyperpigmentation of the skin and guttate hypomelanotic lesions, photophobia,
      abnormal hair, developmental delay, and recurrent bronchitis. Skin histology
      showed pigmentation incontinence with numerous melanophages. Electron microscopy
      showed a very high number of melanosomes and some degenerating keratinocytes.
      These features correspond to a rare genodermatosis, the X-linked reticulate
      pigmentary disorder with systemic manifestations. Skewed X-inactivation patterns
      were detected in the mother's lymphocytes.

PMID- 15844785
TI  - The importance of excluding 13q deletion mosaicism in the diagnosis of
      retinoblastoma associated with dysmorphic features.

PMID- 15844786
TI  - Medullary thyroid carcinoma in a child with a new RET mutation and a RET
      polymorphism.
AB  - We report a 12 year old boy with an isolated medullary thyroid carcinoma (MTC). A
      mutation analysis of the RET-proto-oncogene in this boy showed an in frame
      insertion-deletion mutation (insTTCTdelG) at codon 666 of the RET proto-oncogene.
      This RET mutation has not been reported previously. The boy's mother and his 82
      year-old maternal grandfather showed the same mutation. None of the two ever
      showed symptoms of MTC. The mother underwent a preventive total thyroidectomy and
      pathological examination showed C-cell hyperplasia and early MTC. Further genetic
      analysis showed that the boy inherited a well-known coding polymorphism in exon
      11 (G691S) from his father. Therefore the boy is a compound heterozygote for the
      insertion-deletion mutation at codon 666 and the G691S polymorphism in the RET
      gene. We hypothesize that the insTTCTdelG mutation at codon 666 is associated
      with low penetrance for MTC and that the young age of MTC in the reported child
      results most likely from the additive effects of both mutations (insTTCTdelG and
      G691S).

PMID- 15844788
TI  - Primary autosomal recessive microcephaly: a novel clinical phenotype.

PMID- 15844787
TI  - Hypothalamic hamartoma, cerebellar hypoplasia, facial dysmorphism and very
      atypical combination of polydactyly: is it a new variant of oro-facio-digital
      syndrome?
AB  - We describe a newborn with multiple congenital anomalies consistent with an oro
      facio-digital syndrome (OFDS). These are a group of inherited syndromes that have
      in common anomalies of the tongue (bifid or lobulated tongue with hamartomas),
      the face (median cleft lip) and the digits (brachydactyly, polydactyly,
      clinodactyly and/or syndactyly). OFDS has been classified into 11 types. The case
      described in this paper had manifestations overlapping with OFDS II (Mohr) and
      OFDS IV (Mohr-Majewski) and OFDS VI (Varadi). We propose that the present patient
      has a new variation of the OFDS due to the co-existence of the very atypical
      combination of polydactyly, cerebellar hypoplasia, hypothalamic hamartoma and
      classical facial findings of OFDS.

PMID- 15844789
TI  - Unusual clinical syndrome in a boy with 45,X/46,XY mosaicism.

PMID- 15844790
TI  - A newborn infant with infantile spinal muscular atrophy associated with trisomy
      21 and congenital hypothyroidism.

PMID- 15844791
TI  - Unethical business practices in U.S. health care alarm physician leaders.
AB  - Learn the results of ACPE's recent survey on ethical business practices and find
      out why physician executives are very concerned about the impact unethical
      behaviors appear to be having on health care.

PMID- 15844792
TI  - Pros and cons: the eye of the beholder.

PMID- 15844793
TI  - Ethical challenges abound.

PMID- 15844794
TI  - Practicing preventive ethics-the keys to avoiding ethical conflicts in health
      care.

PMID- 15844795
TI  - The legal implications for health care's bad business practices.

PMID- 15844796
TI  - Excerpts from: On the take.

PMID- 15844797
TI  - A measure of professionalism.

PMID- 15844798
TI  - Lantern of Diogenes: is "honest physician" a 21st century oxymoron?

PMID- 15844799
TI  - Professionalism in medicine: the new authority.
AB  - Examine some ways that the health care profession could regain lost ground and
      begin exerting more influence in the marketplace to help offset the pressures
      from insurance companies, consumers, and the government.

PMID- 15844800
TI  - The life of a Chinese American female physician executive.

PMID- 15844801
TI  - Evidence-based medicine. Finding gaps in quality and value (Part 2).

PMID- 15844802
TI  - Getting from here to there in health care.

PMID- 15844803
TI  - Decision making under uncertainty: Part 2.

PMID- 15844804
TI  - Say what?

PMID- 15844805
TI  - Eliminating the carriage of Salmonella enterica serovar Enteritidis in domestic
      fowls by feeding activated charcoal from bark containing wood vinegar liquid
      (Nekka-Rich).
AB  - The protective efficacy of activated charcoal containing wood vinegar liquid
      (Nekka-Rich) against intestinal infection with Salmonella enterica serovar
      Enteritidis was sought. In the present study, the adsorption effects of activated
      charcoal of Nekka-Rich on S. Enteritidis and normal bacterial flora in the
      intestine, Enterococcus faecium, were examined. S. Enteritidis was effectively
      adsorbed by activated charcoal of Nekka-Rich. On the other hand, activated
      charcoal of Nekka-Rich showed lower binding capacity to E.faecium. The effects of
      wood vinegar liquid included in Nekka-Rich on the growth of S. Enteritidis and
      normal bacterial flora in the intestine, E. faecium and Bifidobacterium
      thermophilum, were also assessed. Wood vinegar liquid had an inhibitory effect on
      the S. Enteritidis growth, whereas growth of E. faecium and B. thermophilum was
      enhanced by wood vinegar liquid. Furthermore, the protective effects of Nekka
      Rich were evaluated in a challenge chicken model with S. Enteritidis. Chickens
      were fed a basal diet containing Nekka-Rich or immunized with commercially
      obtained S. Enteritidis vaccine and challenged with S. Enteritidis. Significantly
      less fecal excretion of S. Enteritidis was observed in chickens fed Nekka-Rich
      for 10 d after challenge. On d 15 after challenge, S. Enteritidis was not
      isolated from fecal samples. On the other hand, immunization of chickens with S.
      Enteritidis vaccine did not fully inhibit bacterial growth. Fecal excretion of S.
      Enteritidis was consistently observed in the vaccinated chickens after challenge.
      These results suggest that Nekka-Rich would be a good product for eliminating the
      carriage of S. Enteritidis in domestic fowl.

PMID- 15844806
TI  - Comparisons of molting diets on skeletal quality and eggshell parameters in hens
      at the end of the second egg-laying cycle.
AB  - A study was conducted to evaluate skeletal quality and eggshell parameters of
      molted hens at the end of the second laying cycle. Sixty Single Comb White
      Leghorn hens were used for this study. There were 2 controls and 4 molting
      treatments: full-fed control 1 (82 wk old; FF1), full-fed control 2 (122 wk old;
      FF2), feed withdrawal (FW), 100% alfalfa (A100), 90% alfalfa/10% layer ration
      (A90), and 70% alfalfa/30% layer ration (A70). At the end of the second laying
      cycle (approximately 122 wk of age), hens were euthanized by CO2. Tibia and femur
      were collected. There were no differences in bone parameters between FF1 and FF2
      (P > 0.05) hens. There were no differences in bone parameters among the different
      molting dietary treatments (P > 0.05). In the eggshell parameters, the FF2 hens
      exhibited heavier egg weights than the FF1 (P < 0.05), whereas the percentage
      shell and egg production of the FF1 birds were significantly higher than those of
      the FF2 birds. Shell weights of the FW and A90 birds were significantly heavier
      than that of the A100. The correlation analysis showed that overall bone
      parameters were negatively correlated with eggshell parameters. Bone parameters
      were highly correlated with each other. Shell weight, percentage shell, and shell
      thickness were positively correlated with each other, whereas egg weight was
      negatively correlated with percentage shell. These results suggest that age of
      hens and molting dietary treatments influence egg parameters, and eggshell
      formation is closely related to bone metabolism in laying hens.

PMID- 15844807
TI  - Selection strategies for body weight and reduced ascites susceptibility in
      broilers.
AB  - Ascites syndrome is a metabolic disorder in broilers. Mortality due to ascites
      results in significant economic losses and has a negative impact on animal
      welfare. It has been shown that genetic factors play a considerable role in
      susceptibility of birds to ascites, which offers perspectives for selection
      against this syndrome. The aim of the present study was to evaluate the
      consequences of alternative selection strategies for BW and resistance to ascites
      syndrome using deterministic simulation. In addition to the consequences of
      current selection (i.e., selection for increased BW only) alternative selection
      strategies including information on different ascites-related traits measured
      under normal or cold conditions and the consequences of having information on the
      underlying genes (i.e., MAS) were quantified. Five different breeding schemes
      were compared based on the selection response for BW, ascites susceptibility, and
      the rate of inbreeding. Traits investigated in the index as indicators for
      ascites were hematocrit value (HCT) and ratio of right ventricle to the total
      ventricular weight of the heart (RV:TV). The results indicated that by ignoring
      ascites susceptibility in the breeding goal, the gain for BW is 130 g and the
      birds will become more susceptible to ascites. Testing 50% of the birds under
      cold temperature conditions and including information of ascites related traits
      (HCT and RV:TV) measured under normal and cold conditions makes it possible to
      achieve a relatively high gain for BW (111.4 g) while controlling the genetic
      level for ascites susceptibility (selection response was 0). The results of
      scenarios including QTL information of ascites susceptibility showed that QTL
      information could be used very effectively in controlling ascites susceptibility.

PMID- 15844808
TI  - Correlated responses to divergent selection for phytate phosphorus
      bioavailability in a randombred chicken population.
AB  - The current study was undertaken to evaluate the correlated responses to 3
      generations of divergent selection for phytate phosphorus bioavailability (PBA)
      in the Athens-Canadian randombred chicken population. The traits studied were BW
      at 4 wk of age, BW gain (BWG), feed consumption (FC), and feed conversion ratio
      (FCR) during a period of 3 d. The first evaluation criterion was the cumulated
      divergent correlated response (CR(C)), which was calculated as the line
      difference of the least square means of phenotypic values for each trait at a
      given generation after adjustment for sex and hatch effects. The results showed a
      consistent correlated response in BW across generations. The CR(C) at generation
      G3 was 26.8 g (P < 0.01). The chickens in the low PBA line (L line) had higher BW
      than the high PBA line (H line). The CR(C) for BWG, FC, and FCR were significant
      (P < 0.05) only at G3. The second evaluation criterion was the average best
      linear unbiased prediction estimated breeding value (EBV). The results showed
      asymmetric genetic trends in BW, BWG, and FC, and the correlated responses were
      mainly due to the genetic changes that occurred in H line because little genetic
      change occurred in L line across generations. At G3, the line differences of EBV
      were close to the CR(C) values for all the traits except FCR. This suggested that
      CR(C) and EBV criteria would tend to be consistent with the increase across
      generations. However, at G1 and G2, the line differences of the EBV actually
      deviated from the CR(C) values for BWG and FC. The inconsistency could be
      attributed to experimental errors and genetic drift that were not accounted by
      the fixed model for obtaining CR(C).

PMID- 15844809
TI  - Effect of age on utilization of selenium by chickens.
AB  - Utilization of selenium was examined in slow-growing laying-type chickens (SG)
      and in fast-growing broiler hybrids (FG) fed ad libitum on a diet with 265 microg
      of selenium/kg, including 128 microg of selenium added as sodium selenite. To 40
      d of age, coefficients of selenium retention increased (P < 0.05) daily in the SG
      and FG groups by 0.76 and 0.61%, respectively. From 40 to 100 d, the regression
      coefficients were not significant. Coefficients of selenium retention and
      retention per unit of body gain were higher in SG chickens. The influence of age
      on selenium content in BW gain of birds was evident (P < 0.01). From 5 to 40 d,
      allometric coefficients were 1.444 and 1.070 for SG and FG, respectively, and
      from d 40 to 100 the corresponding values were 1.282 and 1.081, respectively.

PMID- 15844810
TI  - Caponization and testosterone implantation effects on blood lipid and lipoprotein
      profile in male chickens.
AB  - To understand the role of lipid metabolism in increasing body fat accumulation
      after caponization of male chickens, trials were conducted to determine the
      effects of levels of testosterone implantation on lipoprotein composition. Male
      chickens were caponized at 12 wk and selected at 16 wk for a 10-wk feeding
      experiment. Fifteen male and 15 caponized (capon) chickens were used in trial 1.
      Ten sham operated chickens (sham) and 40 capons were randomly divided among 4
      treatments in trial 2; the treatments were as follows: implantation of
      cholesterol (1.62 mm i.d. x 3.16 mm o.d., 9.24+/-0.36 mg) or implantation of
      testosterone at low (1 mm i.d. x 3 mm, o.d., 5.88+/-0.23 mg), medium (1.62 mm
      i.d. x 3.16 mm, o.d., 9.81+/-0.17 mg), or high (2 mm i.d. x 4 mm, o.d., 16.7+/
      0.24 mg) dose. The results of trial 1 showed that caponization decreased (P <
      0.05) blood testosterone concentrations and increased (P < 0.05) abdominal fat
      weight and relative abdominal fat weight in capons. Caponization also increased
      low density lipoprotein (LDL), high density lipoprotein (HDL), LDL protein, and
      HDL protein and decreased LDL-free cholesterol (LDL-FC), HDL-FC, and HDL
      phospholipid (HDL-PL) percentages (P < 0.05). In trial 2 capons implanted with
      increasing testosterone levels exhibited proportional increases in blood
      testosterone concentration, although blood testosterone concentration in
      implanted capons were not fully restored to those of the sham group. High dose
      testosterone implantation inhibited abdominal fat accumulation and increased
      glucose and glycerol concentrations compared with the cholesterol implantation.
      Caponization of male chickens decreased the androgen level and increased the
      blood triacylglyceride content. Caponization also changed the lipoprotein
      profiles, which resulted in increased lipid storage capacity. The testosterone
      concentration, therefore, must achieve threshold concentrations to inhibit lipid
      accumulation in the testosterone implanted capon.

PMID- 15844811
TI  - An acute inflammatory response alters bone homeostasis, body composition, and the
      humoral immune response of broiler chickens.
AB  - To quantify the effects of an acute phase response in broilers, chicks were
      injected with 1 mg/kg Escherichia coli lipopolysaccharide (LPS) at 15 and 23 d.
      Lipopolysaccharide injection increased feed/gain (P = 0.03), increased liver
      weight (P = 0.09), and decreased tibia calcium (P = 0.05) and breaking strength
      (P < 0.04) by d 28. In a second experiment, 3 d postinjection of chicks at d 31,
      LPS decreased BW (P < 0.01), breast weight (P = 0.08), and tibia breaking
      strength (P = 0.05), and increased liver weight (P < 0.01), mortality (P = 0.05),
      and titers to bronchitis and Mycoplasma gallisepticum that were induced by
      vaccination at hatch or by field exposure, respectively (P = 0.04). For
      experiment 3, chicks were challenged with LPS at 23d and 27d. Lipopolysaccharide
      injected chicks had decreased BW (P = 0.06), feed consumption (P = 0.05), tibia
      weight (P< 0.01), and breaking strength (P < 0.01), and increased feed/gain (P <
      0.01), liver weight (P < 0.01), and plasma ionized calcium level (P = 0.08). For
      experiment 4, chicks were injected with 0, 0.33, 0.66, 1.00, or 4.25 mg of LPS/kg
      of BW. There was an inverse relationship between LPS level and BW or bone
      breaking strength. Experiment 5 compared 4 broiler strains. Strain x LPS
      interactions were found for bone breaking strength (P = 0.01). Mortality before
      LPS challenge was inversely correlated to liver weight (r2 = 0.95, P = 0.02) and
      bone breaking strength (r2 = 0.99, P = 0.01) only after an LPS challenge.

PMID- 15844812
TI  - Effect of dietary calcium and vitamin D3 on calcium and phosphorus retention in
      white Pekin ducklings.
AB  - Higher concentrations of Ca in the diet may decrease phytate-phosphorus
      hydrolysis because of chelation of Ca with the phytin molecule. In experiment 1,
      drakes were fed 0.74, 0.85, 0.95, or 1.11% Ca (analyzed) from 7 to 18 d of age (6
      birds/cage, 8 cages/diet). Intestinal mucosa was collected at 18 d of age from
      birds fed 0.74 and 1.11% Ca for determination of intestinal phytase activity. In
      experiment 1, 17 d BW gain and feed consumption exhibited a quadratic response to
      increasing concentrations of Ca and were found to be maximal for ducks fed the
      0.95% Ca diet. Toe ash percentage (18 d) had a quadratic response to increasing
      concentrations of Ca with a maximal response for birds fed the 0.85% Ca diet.
      Increasing dietary Ca did not affect P retention from 15 to 17 d of age or
      intestinal phytase activity and brush border vesicle Ca concentration. A positive
      correlation was found between the Vmax and the Ca concentration within the
      vesicles (r = 0.59, P < 0.02), suggesting that the vesicle Ca concentration did
      not negatively affect the kinetics of the phytase assay. In experiment 2, drakes
      were fed 0.6, 0.8, 1.0, or 1.2% Ca (formulated) with 826 or 8,260 ICU/kg of
      vitamin D3 from 0 to 13 d of age. There was no response to increasing
      concentrations of Ca for performance characteristics or bone ash measurements.

PMID- 15844813
TI  - Assessment of potential interactions between phytase and glycosidase enzyme
      supplementation on nutrient digestibility in broilers.
AB  - The effects of microbial 3-phytase and glycosidase enzymes, and their
      interactions, on energy values and nutrient digestibility in diets rich in
      nonstarch polysaccharides (NSP) were studied in diets based on corn, wheat, or
      barley. Four diets were prepared with each cereal grain. One had no enzymes, a
      second had 500 units of phytase, a third had glycosidase enzyme, and a fourth had
      phytase and glycosidase. The glycosidases used were alpha-galactosidase (corn
      diet), xylanase (wheat), and beta-glucanase (barley). Glycosidase decreased
      intestinal viscosity, whereas phytase increased this parameter in corn diets.
      Phytase increased AME in corn diets, whereas beta-glucanase in barley diets
      improved AME and AMEn, and digestibility of dry matter, starch, beta-glucans, and
      lipid. Xylanase in wheat diets improved dry matter and starch digestibility.
      Phytase increased total phosphorus retention in all diets, and significant
      interactions between glycosidase enzymes and phytase were detected in wheat and
      barley diets. Phytase decreased phosphorus excretion in corn and barley diets,
      whereas alpha-galactosidase increased phosphorus excretion in corn diets. Phytase
      in corn diets and beta-glucanase in barley diets increased calcium retention,
      whereas inclusion of xylanase decreased calcium retention in wheat diets. Phytase
      and beta-glucanase decreased calcium excretion in corn- and barley-based diets,
      respectively. An interaction was detected between phytase and beta-glucanase in
      barley diets, in which calcium excretion was reduced. In general, no negative
      interactions between phytase and glycosidase enzymes were found, indicating that
      both types of enzymes may be used together in feeds based on corn, wheat, or
      barley.

PMID- 15844814
TI  - The bioavailability of lysine and phosphorus in distillers dried grains with
      solubles.
AB  - Five experiments were conducted to determine Lys and P bioavailabilities of
      distillers dried grains with solubles (DDGS), which was derived from corn
      fermentation in a modern nonbeverage ethanol plant. In experiment 1, we used the
      precision-fed cecectomized rooster assay and estimated the true digestibility of
      Lys in DDGS to be 75%. In experiments 2, 3, 4, and 5 the relative
      bioavailabilities of Lys and P were assessed using slope-ratio chick growth
      experiments. In experiments 2 and 3, Lys-deficient basal diets containing 0.40 or
      0.60% digestible Lys respectively, were formulated. A linear growth response (P <
      0.05) was observed from the addition of 0.10 and 0.20% L-Lys from L-Lys x HCl and
      10 and 20% DDGS to the basal diets. Body weight gain was regressed on Lys intake
      from L-Lys x HCl and DDGS, and the ratio of the slopes indicated the relative
      bioavailable Lys in DDGS. The values as a percentage of total Lys (0.83) in DDGS
      yielded availability estimates of 80% for experiment 2 and 100% for experiment 3.
      In experiments 4 and 5, a P-deficient basal diet containing 0.12% nonphytate P
      was formulated. A linear growth and tibia bone ash (%) response (P < 0.05) were
      observed from the addition of 0.05 and 0.10% P from K2HPO4 and 2 levels of DDGS
      (5 and 10% for experiment 4 and 7 and 14% for experiment 5). Tibia bone ash (%)
      was regressed on P intake from K2HPO4 and DDGS, and the ratio of slopes indicated
      the relative bioavailability of P in DDGS. The values as a percentage of total P
      (0.74%) in DDGS yielded availability estimates of 68% for experiment 4 and 54%
      for experiment 5.

PMID- 15844816
TI  - Isolation of chicken primordial germ cells using fluorescence-activated cell
      sorting.
AB  - Presently, it is difficult to undertake germ line modification of the chicken
      with primordial germ cells (PGC) because it has been difficult to efficiently
      fractionate the PGC from the total somatic cell population. The objective of this
      study was to develop a method that allows isolation of an enriched population of
      viable PGC from embryonic blood and embryonic gonadal tissue. Blood was harvested
      from early chick embryos (stages 13 to 15), and cells were liberated from the
      gonads of stage 27 chick embryos. Subsequently, viable PGC were labeled with anti
      stage-specific embryonic antigen-1 (SSEA-1), which was detected with goat-anti
      mouse IgM-fluorescein isothiocyanate. Fluorescently labeled cells were sorted
      from the unlabeled cells using fluorescence-activated cell sorting (FACS), and
      the identities of the PGC were confirmed using periodic acid-Schiff (PAS)
      staining or anti-embryonic mouse antigen-1 (EMA-1) staining followed by
      microscopic evaluation. Finally, PGC were sorted from somatic cells of sex
      identified embryos. Less than 0.1% of the blood cell population was collected as
      SSEA-1-positive cells. Similarly, approximately 2% of the gonadal cell population
      were collected as SSEA-1-positive cells. Therefore, fewer (-1,000 to 9,000) PGC
      were recovered from each isolate. Placing the sorted SSEA-1-positive cells on a
      glass slide from a microcentrifuge tube resulted in a recovery rate of 53 to 73%
      relative to the number detected by FACS. Furthermore, the proportions of sorted
      cells that stained with PAS or anti-EMA-1 following sorting were 92+/-4% PAS
      positive and 94+/-1% anti-EMA-1 positive. Finally, the sorted SSEA-1-positive
      cells were maintained in vitro to demonstrate their viability after sorting. It
      was demonstrated that it is possible to label blood and gonadal chicken PGC with
      SSEA-1 and subsequently to sort viable SSEA-1-positive PGC from somatic cells.

PMID- 15844815
TI  - Comparison of broiler performance when fed diets containing corn grain with
      insect-protected (corn rootworm and European corn borer) and herbicide-tolerant
      (glyphosate) traits, control corn, or commercial reference corn.
AB  - A 42-d feeding experiment with growing Ross x Ross 508 broilers showed that the
      nutritional value of insect-protected and herbicide-tolerant corn was comparable
      to that of the genetically similar control and 5 commercial reference corn
      hybrids. MON 88017 provides protection from feeding damage by coleopteran pest
      corn rootworm and is tolerant to the action of glyphosate, the active ingredient
      in the Roundup family of agricultural herbicides. MON 88017 x MON 810 was
      developed by the traditional breeding of MON 88017 with MON 810, which provides
      protection from the European corn borer and other lepidopteran pests. A
      randomized complete block design was used with 8 dietary treatments in each of 5
      replicated blocks of pens. No differences among diets were observed (P > 0.05) in
      performance (final live weights, feed intake, feed conversion, and adjusted feed
      conversion), carcass yield (chill, fat pad, breast, thigh, wing, and drum
      weight), or percentage of moisture, protein, and fat in breast meat and moisture
      and fat in thigh meat. Thigh protein was similar (P > 0.05) in broilers fed diets
      containing MON 88017 x MON 810 and conventional control or all commercial
      reference corns; however, differences (P < 0.05) were noted for the percentage of
      thigh protein among broilers fed the control and 2 of the 5 reference diets,
      attributable to biological variability among the conventional corn hybrids.
      Broilers overall performed consistently and had similar carcass yield and meat
      composition when fed diets containing MON 88017 or MON 88017 x MON 810 as
      compared with those fed the conventional control and commercial diets, supporting
      a conclusion of nutritional equivalence.

PMID- 15844817
TI  - Effects of posthatch feed deprivation on heparan sulfate proteoglycan, syndecan
      1, and glypican expression: implications for muscle growth potential in chickens.
AB  - The heparan sulfate proteoglycans, syndecan-1 and glypican-1 (glypican), are low
      affinity receptors for fibroblast growth factor 2 (FGF2). Because FGF2 stimulates
      skeletal muscle cell proliferation but inhibits differentiation, changes in FGF2
      signaling due to early posthatch feed deprivation may play a significant role in
      modulating muscle growth. To study the effect of early posthatch feed deprivation
      in chickens on heparan sulfate proteoglycan relative protein concentration,
      syndecan-1 expression, and glypican mRNA expression, pectoralis major muscle
      tissue was isolated from pretreatment d 0 chicks and chicks fed or feed deprived
      for 3 d, and after d 3 feeding was resumed in the feed-deprived birds until d 7.
      Heparan sulfate proteoglycan protein concentration was measured by ELISA analysis
      and was significantly decreased in the feed-deprived birds beginning at d 2 (P <
      0.05). The expression of syndecan-1 and glypican was measured by semi
      quantitative reverse transcription PCR. Syndecan-1 expression was unaffected by
      feed withdrawal and refeeding (P > 0.05). Glypican mRNA expression was decreased
      in the muscle tissue from feed-deprived birds at d 3 (P < 0.05), but by d 7,
      after initiating feeding on d 4, it was significantly elevated compared with in
      muscle tissue from chicks maintained on feed (P < 0.05). The results from the
      present study demonstrate that the heparan sulfate proteoglycan protein
      concentration and syndecan-1 and glypican mRNA expressions are differentially
      affected by early posthatch feed deprivation, which may alter signaling events
      associated with muscle growth.

PMID- 15844818
TI  - Effects of aging prior to freezing on poultry meat tenderness.
AB  - The objective of this study was to investigate the effects of aging prior to
      deboning and deep-freezing on the tenderness of cooked broiler breast fillets.
      Broilers (Ross-208) that were 37 and 38 d old were slaughtered in a licensed
      poultry meat plant. After spray chilling, carcasses with BW between 1,080 and
      1,300 g were selected for the study and transported to a chilling room (2 to 4
      degrees C). The whole carcasses were aged for up to 24 h. During the aging
      process, continuous measurements were made of pH values, electric conductivity,
      and firmness of the raw fillets. After the aging process, the carcasses were
      deboned, and the breast fillets were immediately frozen to an internal
      temperature of -20 degrees C. Tenderness was measured both mechanically with a
      Warner-Bratzler shear force device and by sensory testing. The ultimate pH values
      in the fillets were reached during the first 5 h of aging. Electric conductivity
      increased during the whole aging period. During the first hours of aging,
      firmness increased significantly, corresponding with the onset of rigor mortis.
      After between 8 and 9 h of aging, firmness decreased significantly. Shear force
      values of aged fillets also changed significantly; the highest values were found
      at the beginning of aging, which then decreased from the sixth hour. The results
      of the instrumental tenderness measurements were confirmed by the sensory
      evaluations. Implementation of in-plant measurements of firmness, thus, seemed to
      be useful in predicting the sensory quality of poultry meat.

PMID- 15844819
TI  - Impact of antimicrobial ingredients and irradiation on the survival of Listeria
      monocytogenes and the quality of ready-to-eat turkey ham.
AB  - Irradiation is an effective technology in eliminating Listeria monocytogenes, but
      it induces quality changes in meat products at or above specific radiation doses.
      To minimize irradiation-induced quality changes, only low irradiation doses are
      recommended. However, low-dose irradiation provides a chance for some pathogens
      to survive and proliferate during prolonged storage. To solve this problem,
      antimicrobial ingredients [2% sodium lactate (SL), 0.1% sodium diacetate (SDA),
      0.1% potassium benzoate (PB)] and low-dose irradiation were combined and tested
      for their effects on the growth of L. monocytogenes and meat quality. The log10
      reductions of L. monocytogenes in hams following exposure to 1.0 to 2.5 kGy of
      irradiation ranged from 2.0 to 5.0. The D10 values were 0.52 kGy for control ham
      or ham with PB, SL, or PB + SL; 0.49 kGy for ham with SL+SDA; and 0.48 kGy for
      ham with PB + SL + SDA (PSS). Addition of SL + SDA or PB + SL in combination with
      1.0 kGy of irradiation was effective in suppressing the growth of L.
      monocytogenes for about 6 wk when stored at 4 degrees C, whereas 2.0 kGy of
      irradiation was listeriostatic. Ham irradiated with 1 kGy in combination with PSS
      was listeriostatic throughout storage. SL increased firmness of turkey hams, and
      sensory panelists noted that the saltiness was a little higher in products
      containing SL, but its overall impact on quality was minimal. Amounts of benzene
      were detected in irradiated hams with PB, showing PB was not fit as an
      antimicrobial ingredient for irradiated foods. In conclusion, 2% SL and 0.1% SDA
      in combination with low-dose irradiation were effective in ensuring the safety of
      ready-to-eat meat products against L. monocytogenes.

PMID- 15844820
TI  - Penetration of Salmonella enteritidis and Salmonella heidelberg into egg yolks in
      an in vitro contamination model.
AB  - Eggs that harbor Salmonella in their edible contents pose a significant risk of
      transmitting disease to consumers. Although Salmonella deposition inside yolks
      does not usually occur at a high frequency in naturally contaminated eggs,
      bacterial penetration through the vitelline membrane could lead to rapid and
      extensive multiplication in the nutrient-rich yolk contents. The present study
      used an in vitro egg contamination model to assess the ability of Salmonella
      strains to penetrate the vitelline membrane and multiply inside yolks. An S.
      enteritidis strain and 2 Salmonella heidelberg strains, initially inoculated onto
      the outside of the vitelline membrane, were able to enter the yolk contents (at
      frequencies ranging from 10 to 25% of experimentally contaminated eggs) during 24
      h of incubation at 30 degrees C. Variants of these parent strains, obtained by in
      vivo passage into eggs laid by infected hens, penetrated the yolk membrane at
      significantly higher frequencies. These results demonstrate that pathogens such
      as S. enteritidis and S. heidelberg can penetrate into and begin to multiply
      inside the yolks of contaminated eggs during the first day of storage at warm
      temperatures.

PMID- 15844821
TI  - Rearing and laying performance following various step-down lighting regimens in
      the rearing period.
AB  - It is frequently recommended that commercial laying pullets are reared on step
      down lighting regimens, rather than on constant short photoperiods, to help
      achieve BW targets during rear and optimal performance in lay. To evaluate the
      effectiveness of this strategy, Shaver White pullets were maintained on 8-h day
      lengths or given a step-down lighting regimen from 23 to 8 h over periods of
      between 1 and 15 wk. Other pullets, which were initially maintained on 8 h of
      light, were given an abrupt increase in day length prior to transfer to step-down
      lighting at various ages between 1 and 13 wk. All birds were given abrupt
      increments to 14 h at 18 wk and to 16 h at 20 wk to stimulate appetite and
      optimize uniformity of sexual development. Body weights at 6 and 12 wk were
      generally heavier and cumulative feed intakes to 6 wk were greater for birds
      given step-down lighting from 1 wk of age than for constant 8-h controls or birds
      given an initial period on 8-h day lengths prior to step-down lighting. Sexual
      maturity for birds on step-down lighting from 1 wk and for those on < or =5 wk of
      8-h day lengths before transfer to step-down lighting was delayed by about a week
      compared with the constant 8-h controls or birds on 9 wk or more of 8-h day
      lengths before step-down lighting. These delays in sexual maturity resulted in a
      lower BW at 18 wk. Body weight uniformity at 18 wk was improved by step-down
      lighting, whether it was given from 1 wk or after a period of 8-h day lengths.
      Despite step-down lighting resulting in larger initial feed intakes and improved
      early growth, there was no significant improvement in egg numbers, egg weight,
      egg mass, feed intake, shell deformation, or albumen height compared with
      constant 8-h controls. Differences in egg output were generally the consequence
      of photoperiodically induced changes in sexual maturity.

PMID- 15844822
TI  - Antibiotic growth promoters in agriculture: history and mode of action.
AB  - This report will review the history of antibiotic growth promoter (AGP) use in
      the animal industry, concerns about development of antimicrobial resistance, and
      response in the European Union and United States to these concerns. A brief
      description of the history of legislation regarding feed use of antimicrobials in
      Denmark and the experience of animal producers following the 1998 ban will serve
      to illustrate the consequences on animal performance and health of withdrawing
      the approval for this use. The biological basis for antibiotic effects on animal
      growth efficiency will consider effects on intestinal microbiota and effects on
      the host animal and will use the germ-free animal to illustrate effects of the
      conventional microflora. The probability that no single compound will replace all
      of the functions of antimicrobial growth promoters will be considered, and
      methods to consolidate and analyze the enlarging database will be discussed.

PMID- 15844823
TI  - Identification and surveillance of antimicrobial resistance dissemination in
      animal production.
AB  - Antimicrobial resistance is a growing problem in human medicine, and concern has
      been expressed that use of antimicrobials in animals may be a contributing
      factor. Although the majority of human pathogens showing antibiotic resistance
      have no link with animals, the issue of animal use of antimicrobials remains
      controversial, particularly with respect to antibiotic growth promoters (AGP).
      The European Union (EU) has withdrawn as AGP some compounds that remain in use in
      the United Sates. This difference in availability allows comparisons to be made
      of antimicrobial resistance outcomes with and without use of an AGP. Such
      comparisons so far show little apparent measurable benefit to human health
      resulting from the EU removal of AGP, and there is evidence of increased use of
      therapeutic antibiotics in animals to treat an apparent increased incidence of
      clinical disease. Microbial risk assessments are important in judging
      quantitatively or qualitatively whether the risk of using a particular AGP is
      acceptable in terms of potential hazard to human health. Resistance surveillance
      is an essential part of such microbial risk assessments, but such surveillance
      should be carefully planned to avoid confounding factors that could invalidate
      any conclusions.

PMID- 15844824
TI  - Novel preharvest strategies involving the use of experimental chlorate
      preparations and nitro-based compounds to prevent colonization of food-producing
      animals by foodborne pathogens.
AB  - Foodborne diseases caused by enterohemorrhagic Escherichia coli, Salmonella, and
      Campylobacter species are of public health and economic significance. Shedding of
      these pathogens during production and slaughter are risks for contamination of
      products for human consumption. Consequently, strategies are sought to prevent or
      reduce the carriage of these pathogens in food animals before slaughter.
      Experimental products containing chlorate salts have been proven efficacious in
      reducing concentrations of E. coli and Salmonella Typhimurium in the gut of
      cattle, sheep, swine, and poultry when administered as feed or water additives.
      Mechanistically, chlorate selectively targets bacteria expressing respiratory
      nitrate reductase activity, such as most members of the family
      Enterobacteriaceae, as this enzyme catalyzes the reduction of chlorate to lethal
      chlorite. Most beneficial gut bacteria lack respiratory nitrate reductase
      activity, and thus the technology appears compatible with many bacteria
      exhibiting competitive exclusion capabilities. More recently, select
      nitrocompounds have been investigated as potential feed additives, and although
      these nitrocompounds significantly reduce pathogens on their own, evidence
      indicates that they may most effectively be used to complement the bactericidal
      activity of chlorate. A particularly attractive aspect of the nitrocompound
      technology is that, as potent inhibitors of ruminal methanogenesis, they may
      allow producers the opportunity to recoup costs associated with their use. At
      present, neither chlorate nor the nitrocompounds have been approved as feed
      additives by the US Food and Drug Administration, and consequently they are not
      yet available for commercial use.

PMID- 15844825
TI  - Alternatives to antibiotics: utilization of bacteriophage to treat colibacillosis
      and prevent foodborne pathogens.
AB  - Bacteriophages are viruses that infect and kill bacteria. Bacteriophage do not
      infect animal and plant cells, which makes them a potentially safe alternative to
      antibiotics. We have been conducting research on the efficacy of bacteriophage to
      prevent and treat colibacillosis in poultry. Bacteriophages that were lytic to a
      non-motile, serotype 02 isolate of Escherichia coli were isolated from municipal
      wastewater treatment plants and poultry processing plants. This E. coli isolate
      is pathogenic to poultry, causing severe respiratory and systemic infections. Two
      bacteriophage isolates were selected for use in studies designed to determine the
      efficacy of these bacteriophage to prevent and treat severe colibacillosis in
      poultry. Colibacillosis was induced by injecting 6 x 10(4) cfu of E. coli into
      the thoracic air sac when birds were 1 wk of age. Initial studies demonstrated
      that mortality was significantly reduced from 85 to 35% when the challenge
      culture was mixed with equal titers of bacteriophage, and the birds were
      completely protected when the challenge culture was mixed with 10 pfu of
      bacteriophage. In subsequent studies, we have shown that an aerosol spray of
      bacteriophage given to birds prior to this E. coli challenge could significantly
      reduce mortality even when given 3 d prior to the E. coli challenge. Our research
      on treating colibacillosis in poultry has demonstrated that an intramuscular
      injection of bacteriophage given 24 or 48 h after the birds were challenged
      rescued the birds from this severe E. coli infection. We have demonstrated that
      bacteriophage can be used to prevent and treat colibacillosis in poultry and may
      provide an effective alternative to antibiotic use in animal production.

PMID- 15844826
TI  - Antibodies: an alternative for antibiotics?
AB  - In 1967, the success of vaccination programs, combined with the seemingly
      unstoppable triumph of antibiotics, prompted the US Surgeon General to declare
      that "it was time to close the books on infectious diseases." We now know that
      the prediction was overly optimistic and that the fight against infectious
      diseases is here to stay. During the last 20 yr, infectious diseases have indeed
      made a staggering comeback for a variety of reasons, including resistance against
      existing antibiotics. As a consequence, several alternatives to antibiotics are
      currently being considered or reconsidered. Passive immunization (i.e., the
      administration of more or less pathogen-specific antibodies to the patient) prior
      to or after exposure to the disease-causing agent is one of those alternative
      strategies that was almost entirely abandoned with the introduction of chemical
      antibiotics but that is now gaining interest again. This review will discuss the
      early successes and limitations of passive immunization, formerly referred to as
      "serum therapy," the current use of antibody administration for prophylaxis or
      treatment of infectious diseases in agriculture, and, finally, recent
      developments in the field of antibody engineering and "molecular farming" of
      antibodies in various expression systems. Especially the potential of producing
      therapeutic antibodies in crops that are routine dietary components of farm
      animals, such as corn and soy beans, seems to hold promise for future application
      in the fight against infectious diseases.

PMID- 15844827
TI  - Alternatives to antibiotics: chemical and physical antimicrobial interventions
      and foodborne pathogen response.
AB  - Successful control of foodborne pathogens requires placement of chemical and
      physical hurdles in the preharvest and postharvest food production sectors.
      Pathogens may also encounter indigenous antimicrobials in foods including certain
      botanical compounds that have historically been used for flavor enhancement as
      well as preservation. Chemical additives have traditionally included organic
      acids to control microbial contamination in foods and feeds. However, there is
      some concern that continuous application of certain chemical antimicrobials can
      lead to a buildup of microbial resistance. This creates problems if foodborne
      pathogens survive and develop resistance to a variety of environmental stressors
      encountered in pre- and postharvest animal production. To expand the diversity of
      potential antimicrobials that have practical application to food animal
      production requires exploring the interaction between the food matrix and
      foodborne pathogens. There is potential for isolating antimicrobial compounds
      that exhibit mechanisms unrelated to conventional antimicrobial compounds.
      However, understanding the potential for novel antimicrobial compounds in foods
      and feeds will require the physiological examination of foodborne pathogen
      response under experimental conditions comparable to the environment where the
      pathogen is most likely to occur. Research on foodborne Salmonella pathogenesis
      is extensive and should provide a model for detailed examination of the factors
      that influence antimicrobial effectiveness. Analysis of pathogen response to
      antimicrobials could yield clues for optimizing hurdle technologies to more
      effectively exploit vulnerabilities of Salmonella and other foodborne pathogens
      when administering antimicrobials during food and feed production.

PMID- 15844828
TI  - Hawthorn: potential roles in cardiovascular disease.
AB  - Hawthorn (Crataegus) may play a role in the prevention and treatment of
      cardiovascular diseases such as hypertension, hyperlipidemia, and in particular,
      congestive heart failure. Evidence is accumulating that hawthorn may induce anti
      ischemia/reperfusion-injury, anti-arrhythmic, hypolipidemic and hypotensive
      effects. These beneficial effects may in part be due to the presence of
      antioxidant flavonoid components. While a number of studies have been performed
      to evaluate the clinical efficacy of hawthorn, an international, multicenter,
      prospective clinical study including a large number of New York Heart Association
      (NYHA) class II/III heart failure patients is ongoing to test hawthorn's long
      term therapeutic effects. Further clinical trials as well as pharmacokinetic and
      mechanistic studies are needed to explore and confirm its effectiveness, safety
      and pharmacological mechanism.

PMID- 15844829
TI  - Effect of astragalosides on intracellular calcium overload in cultured cardiac
      myocytes of neonatal rats.
AB  - Astragalosides were the main active components from a native Chinese herb
      Astragalus membranaceus. Recent studies have shown that Astragalosides have a
      protective effect on myocardial injury in rats. The present study was designed to
      investigate the effect of Astragalosides on intracellular calcium overload and
      sarcoplasmic reticulum calcium load (SR Ca2+ load) in cultured cardiac myocytes
      from neonatal rats. Astragalosides (100 microg/ml) were incubated in the presence
      of isoproterenol (ISO) (10(-5) M) for 72 hours in cardiomyocytes. Metoprorol (10(
      6) M), a beta1-selective antagonist, was cultured in the same condition as
      Astragalosides. The result showed that intracellular calcium concentration
      ([Ca2+]i) and SR Ca2+ load increased in ISO-treated cardiac myocytes as compared
      to control (P < 0.01). Astragalosides prevented ISO-induced increase in [Ca2+]i
      and SR Ca2+ load. Metoprolol also inhibited those increase. The mRNA expression
      and activity of sarcoplasmic reticulum Ca2+ ATPase (SERCA) were enhanced
      following ISO treatment in cardiac myocytes, and these increases were inhibited
      by Astragalosides or metoprolol (P < 0.05). The decrease of superoxide dismutase
      (SOD) activity and the elevation of intracellular maleic dialdehyde (MDA) were
      observed after ISO treatment in cardiac myocytes. Both Astragalosides and
      metoprolol restored the SOD activity and reduced the level of MDA. We conclude
      that Astragalosides have the effects on reducing [Ca2+]i and SR Ca2+ load,
      enhancing free radical removal and decreasing lipid peroxidation in ISO-treated
      cardiomyocytes, which might account for their protective effect on myocardial
      injury.

PMID- 15844830
TI  - Induction of apoptosis in human oral cancer cell lines, OC2 and TSCCa, by
      chingwaysan.
AB  - Chingwaysan, a Chinese herbal formula, contains Cimicfugae Rhizoma, Rehmanniae
      Radixet Rhizoma, Moutan Radicis Cortex, Coptidis Rhizoma and Angelicae Sinensis
      Radix. This medicine is well-known for its curing power for ulcerated gums,
      toothaches, cheek boils and bleeding gingiva. However, no reports can be found on
      its application in the treatment of oral cancers. We are therefore interested in
      whether Chingwaysan is capable of causing abnormal apoptosis processes, and
      whether this condition can be rectified through Chingwaysan herb treatment. We
      used aqueous extract to treat OC2 and TSCCa cells (both are human oral cancer
      cell lines) with different Chingwaysan concentrations (0, 10, 25, 50, 75 and 100
      microl/ml). The MTT (3, (4, 5-dimethyl-thiazol) 2, 5-diphenyl-tetraxolium
      bromide) reduction assay was employed to quantify the differences in cell
      activity and viability. DNA ladder formation on agarose electrophoresis was also
      performed. The bax expression level was monitored using immunoblotting
      techniques. The patterns of the changes in expression were scanned and analyzed
      by NIH image 1.56 software. Taken together, drastic morphological changes,
      reduced cell viability and the presence of inter-nucleosomal DNA fragmentation
      all indicated that Chingwaysan is capable of inducing apoptosis in OC2 and TSCCa
      cell lines. Furthermore, the accumulation of wild type bax protein significantly
      increased in a dose-dependent manner upon treatment with Chingwaysan. In
      conclusion, Chingwaysan can induce apoptosis via a bax-dependent pathway in cells
      from these two particular oral cancer cell lines.

PMID- 15844831
TI  - Anti-inflammatory activity of CML-1: an herbal formulation.
AB  - CML-1 is a purified extract from a mixture of 13 Oriental herbs (Achyranthis
      Radix, Angelicae Gigantis Radix, Cinnamomi Cortex Spissus, Eucommiae Cortex,
      Glycyrrhizae Radix, Hoelen, Lycii Fructus, Paeoniae Radix, Rehmanniae Radix
      Preparata and Atractylodis Rhizoma, Zingiberis Rhizoma, Zizyphi Semen, Acori
      Graminei Rhizoma) that have been widely used for the treatment of inflammatory
      diseases in Asia. The aim of this study was to investigate the anti-inflammatory
      and analgesic potential of CML-1. The animals used in this study were
      administered either vehicle or CML-1 (30, 100, 300 and 600 mg/kg) orally. The
      vascular permeability induced by acetic acid was significantly reduced by CML-1
      in all doses. The swelling of the rat's hind paw induced by carrageenan was
      significantly inhibited by CML-1 in doses of 100, 300 and 600 mg/kg. In the case
      of rheumatoid arthritis induced by complete Freund's adjuvant in rats, the
      treatment with CML-1 at a dose level of 300 mg/kg inhibited edema. CML-1 at a
      dose level of 600 mg/kg inhibited acetic acid-induced writhing syndrome, however
      it did not have any anti-nociceptive action in the Randall-Selitto assay or the
      hot plate test. Our findings suggest that CML-1 has a potent anti-inflammatory
      activity.

PMID- 15844832
TI  - Effect of kami-kihi-to (jia-wei-gui-pi-tang) for experimental osteopenia.
AB  - In order to examine the effects of Kami-kihi-to (KKT or Jia-Wei-Gui-Pi-Tang) on
      osteopenia, we measured bone mineral density using computed X-ray absorptometry
      and monitored metabolism and bone tissue in an ovariectomized (OVX) rat model.
      Bone mineral density was significantly lower in the OVX group than in normal
      group 3 months after ovariectomy. However, the bone mineral density of the OVX
      group administered KKT was clearly higher than that of the untreated OVX group.
      Locomotor activity was regular in the normal group and in the OVX groups before
      administration of KKT. After 6-month administration of KKT, in OVX groups, the
      pattern of locomotor activity became diphasic with clear active and resting
      phases, as was also observed in the normal group. The locomotor activity did not
      decrease in the OVX groups after administration of KKT. At 6 months, the
      continuity of the trabecular bone was higher in the OVX group administered KKT
      than in the untreated OVX group. These results indicate that KKT improved the
      menopausal symptoms and increased the locomotor activity of the OVX group,
      thereby increasing bone mineral density.

PMID- 15844833
TI  - Pharmacological properties of N-095, a drug containing red ginseng, polygala
      root, saffron, antelope horn and aloe wood.
AB  - This study sought to establish a pharmacological profile for N-095, a crude drug
      containing red ginseng, polygala root, saffron, antelope horn and aloe wood. Our
      studies on rats and mice revealed a number of pharmacological properties of this
      novel drug. N-095 increased the forced swimming time in mice and prevented
      gastric ulcers in rats under restraint and water immersion stress conditions at
      100 mg/kg or higher. It also prevented footpad swelling in rats treated with
      lambda-carrageenin and histamine-induced gastric ulcers in rats at 300 mg/kg or
      higher. Furthermore, N-095 augmented the sedative effect in mice induced by
      hexobarbital, which is characterized by a decreased spontaneous motor activity
      and a prolongation of sleeping time. N-095 also stimulated spontaneous
      contractility of the uterus in rats at 1000 mg/kg and 2000 mg/kg and prevented
      hemolysis of erythrocytes by heating. In contrast, N-095 had no effect on the
      respiratory or cardiovascular system or on water and electrolyte regulation in
      rats or mice. These results show that N-095 is a relatively safe drug for use as
      a nutrient or tonic.

PMID- 15844834
TI  - The neuroprotective effects of BNG-1: a new formulation of traditional Chinese
      medicines for stroke.
AB  - BNG-1, a novel mixture of traditional Chinese medicines with a long history in
      the treatment of stroke, exhibited acute neuroprotection effect on rats with
      middle cerebral artery occlusion (MCAO). Anti-ischemic effects were seen in both
      animals receiving BNG-1 before the ischemic insult as well as in animals
      receiving the drug formulation after surgical occlusion of the artery. Anti
      thrombic activity was seen in vitro to inhibit arachidonic acid-induced platelet
      aggregation and in vivo to prolong bleeding time in mice. BNG-1 was also found to
      inhibit several phosphodiesterase (PDE) isoforms with potency order of the
      following rank: PDE 1 > PDE 3 > PDE 6 > PDE 2 > PDE 4 > PDE 5. Other pre-clinical
      results and emerging clinical data coupled with the present findings suggest that
      BNG-1 may be a safe and effective therapy for both the prevention and treatment
      of cerebral stroke. Moreover, the fundamental cellular mechanism underlying its
      therapeutic effects may result from phosphodiesterase inhibition.

PMID- 15844835
TI  - Raising harmonic variation of arterial pulse in dying rats.
AB  - Our previous study revealed that the coefficient of variation of harmonic
      magnitude (HCV) of radial arterial pulse was significantly raised before the
      death of cancer patients. In this study, we recorded the caudate arterial pulse
      of 24 Sprague-Dawley rats that had a fatal dose of urethane injected into their
      abdomens. Twenty rats were dead within 3 hours after the injection and four
      survived. We defined the last 100 minutes of each rat's life as the dying
      process. During the dying process, we found that both the systolic blood pressure
      and diastolic blood pressure dropped steeply during the last 5 minutes. However,
      all HCVs, except HCV1, climbed steeply before the last 5 minutes. The HCV1 of the
      dying rats was significantly higher than that of rats that survived, starting
      from the first minute (P < 0.01). The HCV2 of the dying rats was significantly
      higher than that of the survived rats starting from the 52nd minute (P < 0.05).
      The HCV3 and HCV4 of the dying rats were significantly higher than those of the
      survived rats until the 70th minute and the 80th minute, respectively (P < 0.05).
      Furthermore, HCV2-HCV4 proceeded with the dying process and increased gradually.
      We concluded that HCVs, which failed first in the high-frequency components and
      then in the low-frequency components, could provide physicians with earlier
      information to prevent the coming failure of circulatory system, and could
      reflect quantitatively pathological severity and predict patient outcome. The
      specific Fourier components in the pulse provide more physiological information
      than systolic and diastolic blood pressures.

PMID- 15844836
TI  - Anti-hepatitis C virus effect of citrus unshiu peel and its active ingredient
      nobiletin.
AB  - We investigated the effects of water and ethyl acetate extracts of Citrus unshiu
      peel (Aurantii Nobilis pericarpium) on hepatitis C virus (HCV) absorption in MOLT
      4 cells (a human lymphoblastoid leukemia cell line). By reverse transcription
      polymerase chain reaction (RT-PCR), we showed that both the ethyl acetate layer
      of Citrus unshiu peel extract and fraction 7 decreased HCV absorption in MOLT-4
      cells. Furthermore, we demonstrated that 3',4',5,6,7,8-hexamethoxyflavone
      (nobiletin) is the active ingredient that markedly inhibited HCV infection in
      MOLT-4 cells.

PMID- 15844837
TI  - The effects of Ananas comosus L. leaves on diabetic-dyslipidemic rats induced by
      alloxan and a high-fat/high-cholesterol diet.
AB  - The aim of this study is to demonstrate the effects of Ananas comosus L. leaves
      on diabetic-dyslipidemic rats. Hypoglycemic and hypolipidemic activities of the
      ethanolic extract of Ananas comosus L. leaves (EEACL) were evaluated in normal
      and alloxan-induced diabetic rats by oral glucose tolerance test and an olive oil
      load test. Anti-diabetic, anti-hyperlipidemic and anti-oxidative activities of
      EEACL were also investigated in diabetic-dyslipidemic rats induced by alloxan and
      a high-fat/high-cholesterol diet. EEACL at the dose of 0.40 g/kg significantly
      inhibited the increase in blood glucose in diabetic rats in oral glucose
      tolerance test, but did not cause any hypoglycerimic activity in normal rats. It
      also significantly inhibited the increase in postprandial triglycerides (TG)
      levels in both normal and diabetic rats in olive oil load test. After 15 days of
      treatment of diabetic dyslipidemic rats, EEACL significantly decreased blood
      glucose (-51.0%, P < 0.01), TG (-50.1%, P < 0.01), TC (-23.3%, P < 0.01), LDL-c (
      47.9%, P < 0.01) and glycated albumin (-25.4%, P < 0.01) levels, significantly
      increased serum high-density lipoprotein cholesterol levels (66.2%, P < 0.01) and
      prevented lower body weight of diabetes (11.8%, P < 0.05), significantly lowered
      lipid peroxidation productions of blood (-27.8%, P < 0.01), brain (-31.6%, P <
      0.05), liver (-44.5%, P < 0.01) and kidneys (-72.2%, P < 0.05) compared with
      those in untreated diabetic dyslipidemic rats. These data suggest that EEACL has
      anti-diabetic, anti-dyslipidemic and anti-oxidative activities, which may be
      developed into a new plant medicine for treatment of diabetes and its
      complications.

PMID- 15844838
TI  - Yukmijihwang-tang derivatives enhance cognitive processing in normal young
      adults: a double-blinded, placebo-controlled trial.
AB  - Yukmijihwang-tang (YMJ), also known as Luweidihuang-tang in China, has been
      widely used as a general herbal tonic for hundreds of years in many Asian
      countries. This study examines whether YMJ derivatives (YMJd) enhance cognitive
      ability in normal human subjects and discusses its potential as treatment for
      dementia patients with deficient cognitive ability. Subjects were divided into
      two groups, the placebo-treated group (n = 15) and the YMJd-treated group (n =
      20). K-WAIS tests, a Korean version of an individual intelligence quotient (IQ)
      test, and a P300 latency assessment of event-related potential (ERP) were
      conducted in order to measure changes in cognitive ability before and after 6
      weeks of YMJd treatment. The K-WAIS mean scores of the group treated with YMJd
      were significantly higher than those of the placebo group (p < 0.05), and their
      mean P300 latency was substantially shorter (p < 0.005). These results suggest
      that YMJd treatment accelerates the speed of information processing and enhances
      cognitive ability. YMJd treatment may help dementia patients or the elderly
      recover from cognition deficiencies or degeneration in clinic.

PMID- 15844839
TI  - Efficacy of the kampo medicine xiong-gui-tiao-xue-yin (kyuki-chouketsu-in), a
      traditional herbal medicine, in the treatment of maternity blues syndrome in the
      postpartum period.
AB  - This study was to evaluate the clinical efficacy of Xiong-gui-tiao-xue-yin (Kyuki
      chouketsu-in), a Japanese traditional herbal medicine, in stabilizing postpartum
      psychological state. We enrolled 268 women who had a normal delivery in Osaka
      Medical College Hospital or its affiliated clinics and randomly assigned them to
      the following two groups: a group of 134 women who received Xiong-gui-tiao-xue
      yin (Kyuki-chouketsu-in) at a dose of 6.0 g/day and another group of 134 women
      without Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) (control group). We observed
      2.06-fold and 1.67-fold higher incidences of depressive mood and nervousness,
      respectively, after delivery in the control group than in the Xiong-gui-tiao-xue
      yin (Kyuki-chouketsu-in) group. Within 3 weeks of postpartum, there was a
      significant difference in the incidences of maternity blues between the Xiong-gui
      tiao-xue-yin (Kyuki-chouketsu-in) group (15.7%; 21/134) and the control group
      (32.1%; 43/134) (p = 0.0195). No adverse effects were observed in this study. The
      results of this study demonstrate the beneficial clinical effects of Xiong-gui
      tiao-xue-yin (Kyuki-chouketsu-in) in stabilizing psychological state in the
      postpartum period. Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in) can be expected to
      improve the mental health of women in the postpartum period and prevent maternity
      blues.

PMID- 15844840
TI  - Effects of medicinal herb tea on the smoking cessation and reducing smoking
      withdrawal symptoms.
AB  - Medicinal herbs (21 species) were screened for the antioxidant activity and
      nicotine degradation activity (NDA) in vitro. Eleven of them with higher
      antioxidant activity and NDA were selected for preparation of the medicinal herb
      tea (MHT) and the effects of MHT on smoking cessation and reducing smoking
      withdrawal symptoms were evaluated in 100 male human smokers. Among these
      medicinal herbs, Eugenia aromaticum and Astragalus membranaceus Bunge showed the
      highest antioxidant activity (IC50 of 30.0 microg/mL) and NDA (1.81),
      respectively. MHT showed relatively high antioxidant activity (IC50 of 50.6
      microg/mL) and NDA (1.23). The urinary cotinine level, a metabolite of nicotine,
      increased in the first 2 weeks and greatly decreased from the 2nd to 4th week in
      the MHT taking group, which indicates that MHT accelerates the conversion of
      nicotine into cotinine. Human groups taking MHT for 4 weeks underwent reduced
      smoking withdrawal symptoms compared to the non-MHT taking subjects, and 38% of
      subjects taking MHT succeeded in smoking cessation, while only 12% of non-MHT
      taking subjects succeeded in quitting smoking.

PMID- 15844841
TI  - Qi therapy (external qigong) for chronic fatigue syndrome: case studies.
AB  - The aim of this study was to examine the effects of Qi therapy (QT) on the
      symptoms of chronic fatigue syndrome (CFS), including fatigue and complications.
      QT affected the experience of mental and emotional relaxation in the subjects of
      these case studies, who also gained strength to overcome their pain and fatigue.
      Although the results of these two case studies may not constitute conclusive
      evidence, they provide a foundation for the exploration of QT as a complementary
      therapy in the reduction of negative symptoms of chronic fatigue syndrome.

PMID- 15844842
TI  - The antinociceptive effect of acupressure in rats.
AB  - Acupuncture and acupressure points correlate well with sites on the body that
      have low transcutaneous electrical resistance (TER). Using lightly sedated, adult
      Sprague-Dawley rats, we identified an acupoint (i.e. site with low TER) located
      on the hind limb of the rat and compared the effects of acupressure at this site
      on the nociceptive threshold to an adjacent, non-acupoint site (i.e. site with
      high TER). Focal pressure (55.42 +/- 2.2 g) was applied to the site for 10
      minutes and the tail flick response (TFR) was determined by draping the distal
      portion of the tail over a heated wire (75 +/- 5 degrees C). Three trials were
      performed during each of three randomized conditions (i.e. acupoint, placebo and
      control) and the trials were averaged. All rats tested (5/5) showed a
      statistically significant increase in TFR following 10 minutes of acupressure at
      the acupoint compared to placebo or control trials (p = 0.007). Acupressure at
      the placebo point resulted in a TFR that was not statistically different from the
      control. Systemic administration of naloxone completely abolished the tail-flick
      inhibition induced by acupressure at the acupoint. These data suggest that
      acupressure elicits an antinociceptive effect in rats that is mediated by the
      endogenous release of opioids.

PMID- 15844843
TI  - Acupuncture pain management for patients with cystic fibrosis: a pilot study.
AB  - Cystic fibrosis is the most commonly occurring genetic disorder among Caucasians.
      The purpose of this study was to evaluate the effects of acupuncture for pain
      management in patients with cystic fibrosis; clinical data was obtained regarding
      the integration of acupuncture into the management of pain in patients with
      cystic fibrosis. Visual analog scales were used for pain measurement. Acupuncture
      was found to be effective in decreasing pain complaints in patients with cystic
      fibrosis. No side effects or complications were reported in relation to the
      acupuncture treatment. Acupuncture is effective for managing symptoms and
      illnesses associated with cystic fibrosis. Further randomized controlled trials
      will be necessary to evaluate additional efficacy in pain management and the
      improvement of the quality of life of patients with cystic fibrosis.

PMID- 15844844
TI  - Increase in the vagal modulation by acupuncture at neiguan point in the healthy
      subjects.
AB  - Acupuncture at the Neiguan (P6) point has been shown to lessen nausea and
      vomiting which are related to vagal modulation. This study investigated whether
      acupuncture at the P6 point could improve vagal modulation by using heart rate
      variability analysis. We compared the heart rate variability measures of 39
      subjects receiving acupuncture at the P6 point, 38 subjects receiving sham
      acupuncture, and 34 subjects receiving no treatment at all. The normalized high
      frequency power was used as the index of vagal modulation, and the low-/high
      frequency power ratio was used as the index of sympathovagal balance. The
      normalized high-frequency power after acupuncture increased significantly from
      28.1 +/- 12.6 nu (mean +/- SD) to 30.7 +/- 14.1 nu in the P6 acupuncture group,
      but not in the sham acupuncture (30.6 +/- 13.7 nu versus 31.8 +/- 13.8 nu) or no
      treatment group (30.1 +/- 15.0 nu versus 30.1 +/- 15.7 nu). In both the P6 and
      sham acupuncture groups, the mean RR interval (the intervals between consecutive
      R waves in the electrocardiogram) increased significantly after acupuncture. In
      the no-treatment group, there was no statistical difference in all heart rate
      variability measures in the initial and later sessions. In conclusion,
      acupuncture at the P6 point can increase vagal modulation of the subjects. This
      result may be helpful in the understanding of the mechanism underlying the effect
      of acupuncture or acupressure at P6 on the lessening of nausea and vomiting in
      clinic.

PMID- 15844845
TI  - The assertive community treatment team as a complex dynamic system of care.
AB  - This paper presents a dynamic systems view of assertive community treatment
      (ACT), a recognized evidence-based treatment for adults with severe and
      persistent mental illness (SPMI). It is argued that because an ACT team operates
      as a complex adaptive system (CAS), it engages in the organizational processes of
      "sensemaking" and self-organization, which help to bring order to the actions of
      team members and sustainability of the intervention itself. Consequently,
      successful implementation of ACT requires that management technologies such as
      meaning-creation and design are used in conjunction with traditional "command and
      control" technologies of policies, procedures, processes, and structures.

PMID- 15844846
TI  - Patterns of acute psychiatric hospitalization in Massachusetts.
AB  - This study identifies long-term patterns of patient utilization in acute
      hospitals in Massachusetts based on the 47,787 psychiatric patients. Cluster
      analyses are used to identify six patterns of hospitalization based on the number
      and length of episodes, variety of institutions, length of stay, and time between
      stays. The study demonstrates that while the 74% of one-time patients with short
      stays use only a fifth (18.0%) of the bed days, the highest users were not the
      long-term users, but instead the 22.9% occasional extended-stay patients who use
      70.0% of the total bed days. The study also finds that extending the length of
      the initial stay has little impact on limiting subsequent hospitalization.

PMID- 15844847
TI  - Psychiatric advance directives: perspectives of community stakeholders.
AB  - The present study compares the familiarity with and attitudes about psychiatric
      advance directives among multiple community stakeholders in two Ohio communities.
      One community was involved in a pilot psychiatric advance directive education
      project, and one was not. A total of 272 legal and law enforcement personnel,
      clergy, healthcare professionals, mental health professionals, consumers, and
      family members completed a newly developed measure of opinions about psychiatric
      advance directives. Results indicate significant differences in opinions among
      members of the various stakeholder groups, and implications for advance directive
      education are discussed.

PMID- 15844848
TI  - The effects of federal versus state funding and academic affiliation on mental
      health services.
AB  - This study compares mental health services in three facilities on two domains:
      federal versus state funding and academic affiliation. Data from a cross
      sectional study of psychiatric outpatients is utilized to compare 196 VA patients
      to 337 non-VA patients treated in two state mental health agencies. The strength
      of academic affiliation of the facilities and the degree of participation in
      research and training activities differs significantly across facilities but is
      not associated with quality of care, clinical outcomes, or satisfaction with
      care. Compliance with schizophrenia PORT treatment recommendations is low but
      similar across sites. These findings suggest that, unlike findings from the
      general medical literature, academic affiliation is unrelated to the quality and
      delivery of mental health care.

PMID- 15844849
TI  - Job satisfaction as a function of job level.

PMID- 15844850
TI  - Mental hygiene of the special schools teachers in Kerman, Iran.
AB  - The goal of this research is to identify and study the mental hygiene and its
      related factors (individual, family, organizational) in the Kerman special
      schools teachers. 266 teachers of the special schools of the cities of the
      province Kerman were chosen as the research sample. The necessary data were
      obtained by "questionnaire" which its validity and reliability were determined.
      The statistical analysis of the research findings (by Spearman coefficient test)
      Man-Whithey and Kruskal wallis tests showed that there was a positive and
      meaningful relationship between "Level of education", "service of record" "the
      number of the members of teacher's family", "income", "dwelling-place", "economic
      power", "acceptance of the teacher's job in their family", "leadership style",
      "suitable educational possibilities", "suitable educational space", "job
      satisfaction" with the mental hygiene of the teachers. The results of the
      research also showed that the Kerman special schools teachers enjoyed a
      "relatively desirable" mental hygiene.

PMID- 15844851
TI  - Managed behavioral health care: lessons from Massachusetts.
AB  - Since implementing the first statewide carve-out for behavioral health care in
      1992, Massachusetts has achieved sustained reductions in cost, increases in
      access, and improvements in major quality measures. This introduction to a
      special issue describes the context, linkages with primary care, consumer
      satisfaction, unmet need, performance incentives (a key component of the
      success), stakeholder perspectives, and impacts on special populations.

PMID- 15844852
TI  - Overview of publicly funded managed behavioral health care.
AB  - Using MEDLINE and other Internet sources, the authors perform a systematic review
      of published literature. A total of 109 articles and reports are identified and
      reviewed that address the development, implementation, outcomes, and trends
      related to Managed behavioral health care (MBHC). MBHC remains a work in
      progress. States have implemented their MBHC programs in a number of ways, making
      interstate comparisons challenging. While managed behavioral health care can
      lower costs and increase access, ongoing concerns about MBHC include potential
      incentives to under-treat those with more severe conditions due to the nature of
      risk-based contracting, the tendency to focus on acute care, difficulties
      assuring quality and outcomes consistently across regions, and a potential cost
      shift to other public agencies or systems. Success factors for MBHC programs
      appear to include stakeholder involvement in program and policy development,
      effective contract development and management, and rate adequacy.

PMID- 15844853
TI  - Crossing the divide: primary care and mental health integration.
AB  - This paper describes the views of primary care providers about treating
      depression among adult Medicaid patients and their experiences with managed
      behavioral health care. It also shows the outcomes of an intervention project
      that provides a care manager to facilitate connections among PCPs, patients, and
      behavioral health providers. Despite widespread initiatives to improve depression
      management in primary care and to manage behavioral health services, it appears
      that links between the two systems and the use of evidence-based approaches to
      managing patients are rare. A pilot project to initiate practice redesign, the
      use of a care manager to assist in patient support, and compliance with both
      medical and behavioral health treatment has been shown to improve communication
      and results in positive patient outcomes. Managed behavioral health care can
      result in incentive structures that create gaps between primary care and
      behavioral health systems. This project illustrates an initiative co-sponsored by
      the Massachusetts behavioral health program designed to strengthen links between
      behavioral health and primary care, and increase rates and effectiveness of
      depression treatment.

PMID- 15844854
TI  - Access to services: multiple perspectives from adults with substance abuse
      disorders in Massachusetts.
AB  - This paper describes how 267 Massachusetts adult substance abuse consumers rated
      the substance abuse counseling they have received, their access to behavioral
      health care, and their overall experiences with their health plan or free care.
      This perspective is supplemented with information from administrative data on
      type of care received immediately after the baseline interview, including use of
      wraparound services while in treatment. We hypothesized that consumers in a carve
      out behavioral health plan would view their care more favorably because they had
      a payment source for both substance abuse and mental health care. This hypothesis
      was confirmed. However, it is access to Medicaid insurance, not involvement of
      managed care, that is associated with greater access and higher consumer ratings
      of care.

PMID- 15844855
TI  - Assessing consumer satisfaction in the Massachusetts Behavioral Health
      Partnership.
AB  - From 1999 to 2003, Consumer Quality Initiatives, Inc. (CQI) conducted peer
      interviews with 226 inpatient, 433 day treatment, and 822 outpatient clients of
      programs within the network of the Massachusetts Behavioral Health Partnership.
      Ninety-two percent of day treatment, 93% of the outpatient clients, and 79% of
      inpatient clients rated their care as satisfactory. Clients' views of access,
      appropriateness of services, outcomes of services, what clients liked most, and
      recommendations are summarized. Predictors of satisfaction (e.g., being treated
      with respect and dignity) and outcomes are also shown.

PMID- 15844856
TI  - Performance incentives in the Massachusetts behavioral health program.
AB  - Since 1996, the Massachusetts Behavioral Health Partnership (the
      Partnership/MBHP) has been the behavioral health carve-out vendor for the
      Commonwealth of Massachusetts Primary Care Clinician (PCC) Plan. Its use of
      performance standards and incentives has become one of the central organizing
      activities for both the Commonwealth and the vendor, and one of the program's
      hallmarks. Each year, the Commonwealth uses a participative process for
      generating suggestions for performance incentives, which are then negotiated with
      the Partnership. Success or failure of projects is judged in accordance with
      objective measures developed for each incentive project. From 1996 to 2004, 123
      performance projects have been completed. Some projects have become contract
      requirements, and others have developed into programs or services. The
      performance incentive process blends features of more traditional performance
      standards with performance-based contracting approaches. This process gives both
      the Commonwealth and the Partnership the flexibility to reflect changing state
      policies and to develop a contract that meets the most current needs of members.

PMID- 15844857
TI  - Unmet need for substance abuse treatment of adults in Massachusetts.
AB  - This article presents a methodology to estimate the size and cost of eliminating
      unmet need for substance abuse treatment services among adults who have
      clinically significant substance use disorders, and applies the approach to
      Massachusetts' information. Unmet treatment needs were derived using a statewide
      household telephone survey of 7,251 Massachusetts residents aged 19 and older
      conducted in 1996-1997, and an index of treatment mix and cost information from
      state and Medicaid financial data. The study estimates that 39,450 adult state
      residents (0.81% of the total sample) had a clinically significant past-year
      substance use disorder, but had not received treatment in the past year.
      Providing substance abuse treatment and outreach services to them would have
      required an additional cost of approximately 109 million dollars (17 dollars per
      capita), of which the state's payer of last resort, the Massachusetts Department
      of Public Health Bureau of Substance Abuse Services (BSAS), would need to fund 31
      million dollars (5 dollars per capita). The share paid by BSAS (28%) would
      represent an increase of 42% over its current spending. This paper quantifies an
      important but sometimes overlooked objective of managed care: to improve access
      for substance abusers who need but do not seek treatment.

PMID- 15844858
TI  - Stakeholder perspectives on public managed behavioral care in Massachusetts.
AB  - The 2003 survey of Massachusetts behavioral health providers, as well as
      conference presentations by other key stakeholders, demonstrate continuing high
      ratings for the Massachusetts Behavioral Health Program. Key issues facing the
      program include improving integration, state funding cutbacks, movement into
      performance and outcomes measurement, and concerns about continuing stigma of
      mental illness. These issues are prevalent in other states that can benefit from
      the studies and perspectives of the Massachusetts experience.

PMID- 15844859
TI  - Substance abuse and mental health services for children and adolescents.
AB  - This study examines the initial effects of the Massachusetts Mental Health and
      Substance Abuse Program on 24-hour care for children and adolescents. Analysis of
      Medicaid claims shows that under managed care, access to 24-hour services, the
      number of service users, and admissions increased, while length of stay and
      expenditures decreased. The decomposition of the savings indicated that although
      the increase in admissions would have added an additional 2.7 million dollars to
      expenditures without managed care, the carve-out saved 9.1 million dollars in the
      first year through changes in length of stay, service settings, and price per
      day. The managed care variable was not significant in the regression models
      examining rapid readmission.

PMID- 15844860
TI  - Race, managed care, and the quality of substance abuse treatment.
AB  - The adoption of managed behavioral health care by state Medicaid agencies has the
      potential to increase the quality of treatment for racial minorities by promoting
      access to substance abuse treatment and creating more appropriate utilization
      patterns. This paper examines three indicators of quality for white, Black, and
      Hispanic Medicaid clients who received substance abuse treatment in Massachusetts
      between 1992 and 1996. It evaluates whether a managed behavioral health care
      carve-out in FY1993 had a positive or negative effect on access, continuity of
      care, and 30-day re-admissions. Prior to managed care, access and continuity were
      worse for minorities than for whites. For all clients under managed care, access
      and continuity improved between 1992 and 1996. Access improved more for Hispanic
      clients relative to other racial groups. Continuity improved more for Black
      clients relative to other racial groups. Although seven-day and 30-day re
      admissions also increased following managed care, the rate of increase was not
      significantly greater for minorities. Although managed care had a beneficial
      impact on the quality of treatment for minority clients, the percent of minority
      Medicaid-eligible clients who accessed treatment and the percent who achieved
      continuity of care remained lower than for whites in every year of the study.
      Managed care reduced, but did not overcome, racial disparities in behavioral
      health care.

PMID- 15844861
TI  - A history of cerebral localization.
AB  - The brain has been known to be the center of voluntary movement, sensation, and
      intelligence for centuries. Nevertheless, it was not until the latter third of
      the 19th century that the functions of its different areas were discovered. It
      was the labor of several key men that made possible the accurate localization
      and, furthermore, the resection of brain neoplasms.

PMID- 15844862
TI  - Evolution of vestibular schwannoma surgery: the long journey to current success.
AB  - The extraordinary improvement of patient outcome after surgical treatment for
      vestibular schwannomas is relatively recent and has occurred mainly over the last
      30 years. The introduction of microsurgical techniques has resulted in increasing
      degrees of precise anatomical and functional preservation of the facial and
      cochlear nerves. An expanded microsurgical technique accompanied by continuous
      electrophysiological monitoring has resulted in marked changes in the primary
      goals for this surgery. Whereas in the past the primary goal of vestibular
      schwannoma management was to preserve the patient's life, the objective in
      vestibular schwannoma treatment today is to preserve neurological function. Long
      term follow-up examinations show negligible recurrence rates, indicating that the
      aim of preservation of nerve function does not limit the completeness of tumor
      removal with modern neurosurgical techniques. Despite these advances in
      preserving the anatomical integrity of, for example, the cochlear nerve, losses
      of function and even deafness may occur postoperatively in some cases. Current
      biological and technical research in experimental and clinical settings addresses
      these problems. In this article, the authors report in detail the developments
      achieved in vestibular schwannoma surgery and the great clinicians to whom these
      results can be credited.

PMID- 15844863
TI  - Prizes, lectures, and awards of the American Association of Neurological
      Surgeons/Congress of Neurological Surgeons Section on Tumors.
AB  - An important goal of the Section on Tumors of the American Association of
      Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS) since
      its founding in 1985 has been to foster both education and research in the field
      of brain tumor treatment. As one means of achieving this, the Section awards a
      number of prizes, research grants, and named lectures at the annual meetings of
      the AANS and CNS. After a brief examination of similar honors that were given in
      recognition of pioneering work by Knapp, Cushing, and other early brain tumor
      researchers, the authors describe the various awards given by the AANS/CNS
      Section on Tumors since its founding, their philanthropic donors, and the
      recipients of the awards. The subsequent career of the recipients is briefly
      examined, in terms of the rate of full publication of award-winning abstracts and
      achievement of grant funding by awardees.

PMID- 15844864
TI  - Prognosis of gliomas in the 1970s and today.
AB  - The benefit of the current strategy for diagnosis (magnetic resonance, [MR]
      imaging) and treatment (surgery, chemotherapy, radiotherapy) of gliomas, in
      contrast to the standard treatment in use before MR imaging and the microsurgical
      era, has not yet been determined. A retrospective statistical analysis was
      performed for all patients with glioma who underwent surgery at a single
      institution between 1965 and 1974 (Group I, 88 patients) or 1986 and 1995 (Group
      II, 249 patients). There were no major differences in symptomatology, tumor
      localization, and number of surgical procedures. The mean time until tumor
      diagnosis was significantly shorter in Group II (Group I, 48 weeks; Group II,
      19.5 weeks). Also, the mean time from initial symptoms to surgery was
      significantly shorter for high-grade gliomas in Group II (Group I, 16.3 weeks;
      Group II, 11.7 weeks). For high- as well as low-grade gliomas, there was a clear
      reduction of the perioperative morbidity and mortality rates in Group II.
      Nevertheless, for the postoperative duration of survival, no significant
      differences were demonstrated for high- or low-grade gliomas. Based on the
      results of this study, the perioperative morbidity and mortality rate as well as
      the time from diagnosis to treatment have been remarkably reduced within the last
      30 years. Nevertheless, the overall prognosis for patients with gliomas has not
      changed from the 1970s until today. Thus, the introduction of modern diagnostic
      modalities and surgical procedures has not improved the outcome in patients with
      glioma. Further research to improve the treatment of this disease is urgently
      needed.

PMID- 15844865
TI  - Early evolution of neurological surgery: conquering increased intracranial
      pressure, infection, and blood loss.
AB  - At the end of the 19th century, the early evolution of the specialty of
      neurological surgery was restricted by complications related to infection,
      increased intracranial pressure, and excessive intraoperative blood loss. These
      complications often caused mortality rates of 30 to 50%. An improved
      understanding of pathophysiological factors involved in increased intracranial
      pressure, along with meticulous surgical techniques learned from William Halsted,
      allowed Harvey Cushing to increase the safety of neurosurgical procedures that
      were then in their infancy. Cushing's later development of the "silver clip" and
      incorporation of electrosurgical techniques facilitated safe resection of brain
      tumors previously assumed to be inoperable. These pivotal accomplishments paved
      the way for the establishment of our specialty.

PMID- 15844866
TI  - Effect of hemostasis and electrosurgery on the development and evolution of brain
      tumor surgery in the late 19th and early 20th centuries.
AB  - Hemostatic options available to the surgeon in the late 19th and early 20th
      centuries were limited. The surgical ligature was limited in value to the
      neurological surgeon because of the unique structural composition of brain tissue
      as well as the approaches and operating angles used in this type of surgery. In
      this manuscript the authors review the options available and the evolution of
      surgical hemostatic techniques and electrosurgery in the late 19th and early 20th
      centuries and the impact of these methods on the surgical management of tumors of
      the brain and its coverings.

PMID- 15844867
TI  - History of infection control and its contributions to the development and success
      of brain tumor operations.
AB  - Before advancements in infection control, only conditions that brought patients
      near death warranted the risk of surgical intervention. If patients survived the
      operation, infection was nearly inevitable and death by overwhelming sepsis was
      knocking at their door. In the late 19th century, with the development of germ
      theory by Louis Pasteur and its subsequent application to surgical sterility by
      Joseph Lister, surgeons were able to operate with a substantially reduced risk of
      infection. Consequently, surgeons became more confident and began to explore more
      extravagant procedures, including elective operations within the cranial vault.
      As scientific knowledge expanded in the 20th century, so did the advancement of
      infection control with the use of prophylactic antibiotic drugs, heat
      sterilization of instruments, and microbial barriers. Recent reports have placed
      the rate of complications due to infection between 0.75 and 2.32% for
      intracranial operations.

PMID- 15844868
TI  - Improvements in brain tumor surgery: the modern history of awake craniotomies.

PMID- 15844869
TI  - The transsphenoidal approach. A historical perspective.
AB  - Over the last century, the transsphenoidal approach has evolved into the first
      line method of treatment for sellar as well as select groups of parasellar and
      suprasellar lesions. The journey to its current popularity has been marked by
      controversy and near abandonment in the late 1920s, followed by its renaissance
      in the late 1960s. Despite the profound skepticism with which this procedure was
      viewed, several visionary neurosurgeons persevered through its nadir in
      popularity, preserving this surgical corridor to the skull base. Advances in
      medical and surgical techniques, paralleling an improved understanding of
      pituitary pathophysiology, contributed to its resurgence. The transsphenoidal
      procedures now performed stem from an array of modifications and refinements
      accumulated through nearly 100 years of medical and surgical evolution. This
      era's critical innovations and neurosurgical personalities are the topic of this
      historical overview.

PMID- 15844870
TI  - Percival Bailey and the classification of brain tumors.
AB  - Throughout his illustrious career, Percival Bailey made numerous contributions to
      the fields of neurology, neuroanatomy, psychiatry, neuropathology, and, of
      course, neurosurgery. His expertise, his curiosity about the nervous system, and
      his desire to examine it from all angles were unique. With the exception of
      Harvey Cushing, Dr. Bailey made some of the greatest contributions in the area of
      neuro-oncology at the turn of the last century. In this essay the authors
      summarize the key episodes of Bailey's life and discuss his impact on the
      classification and treatment of human brain tumors.

PMID- 15844871
TI  - Lucien J. Rubinstein: enduring contributions to neuro-oncology.
AB  - Dr. Lucien Rubinstein is best remembered for his significant contributions to the
      field of neuropathology, particularly in the classification of nervous system
      tumors. His accomplishments in basic neuro-oncology and in the formulation of
      diagnostic principles reflected a unique talent for synthesizing fundamental
      clinicopathological concepts based on skillful diagnostic investigation and a
      thorough understanding of neurobiology. Dr. Rubinstein was the leader in the
      establishment of cell cultures from central nervous system (CNS) tumors. He
      meticulously analyzed both light and electron microscopic features of CNS tumors,
      recorded his findings, and patiently drew sketches to be shared generously with
      his colleagues and students. As a pioneer in neuropathology, in his work Dr.
      Rubinstein set the foundation for many enduring concepts in neurosurgery, neuro
      oncology, neurology, and basic tumor biology.

PMID- 15844872
TI  - History of acoustic neurinoma surgery.
AB  - The purpose of this article is to provide insight into the development of surgery
      for acoustic neurinomas throughout the years. The significant contribution of
      surgical authorities such as Cushing, Dandy, and House are discussed. The
      advances in surgical techniques from the very first operations for acoustic
      tumors at the end of the 19th century until today are described, with special
      emphasis on the technological and diagnostic milestones that preceded each step
      of this development.

PMID- 15844873
TI  - Identifying patients at risk for postprocedural morbidity after treatment of
      incidental intracranial aneurysms: the role of aneurysm size and location.
AB  - OBJECT: A decision to treat incidental intracranial aneurysms (IIAs) relies on
      understanding the risks of treatment and weighing them against the those of
      aneurysm rupture. Whereas the natural history of IIAs is currently being studied,
      the risks associated with treating IIAs and factors associated with poor outcome
      need to be clearly established. METHODS: In a consecutive series of 125 patients,
      160 IIAs were treated either surgically (152 cases) or endovascularly (eight
      cases). Postprocedural morbidity was defined as a new neurological deficit
      associated with a score greater than or equal to 3 on the modified Rankin Scale
      or a score of less than 24 on the Mini-Mental Status Examination. Logistic
      regression analysis was used to identify predictors of postprocedural morbidity
      from retrospectively collected data on demographic, clinical, and radiographic
      characteristics. Treatment of IIAs was not associated with any mortality and was
      associated with postprocedural morbidity in 17 (13.6%) of 125 patients (early
      outcome) and eight (6.4%) of patients (late outcome). In the logistic-regression
      model, treatment of aneurysms (>or=13 mm) and posterior circulation aneurysms
      were independently associated with postprocedural morbidity. In patients in whom
      postprocedural neurological deficits developed, 12 (70.6%) of 17 and four (23.5%
      ) of 17 patients harbored aneurysms with broad or calcified necks, respectively.
      Age, comorbidities, multiple aneurysms, specific aneurysm location, and history
      of subarachnoid hemorrhage related to a different aneurysm were not significantly
      associated with poor outcome. CONCLUSIONS: The authors found that IIAs can be
      safely and effectively treated without causing mortality and with a lower
      morbidity rate than previously reported. A combination of radiographic variables
      may be helpful in identifying patients at risk for postprocedural morbidity.

PMID- 15844874
TI  - Prevalence of intracranial aneurysms in first-degree relatives of patients with
      aneurysms.
AB  - OBJECT: A familial predisposition toward cerebral aneurysms has been previously
      described in patients with two or more affected family members. In the present
      study the familial incidence of unruptured intracranial aneurysms was studied in
      96 patients with at least one first-degree relative (parent, sibling, or child)
      in whom a cerebral aneurysm was diagnosed. METHODS: All patients were between 20
      and 70 years of age and underwent three-dimensional fast-spin echo magnetic
      resonance imaging. Sixty-one patients (63.5%) were women. The majority of
      patients (84%) were caucasian and the remainder were Hispanic (13%) or African
      American (3%). No patient suffered a medical condition (excluding hypertension
      and smoking) known to be associated with cerebral aneurysm formation. In four
      patients at least one aneurysm was found (two harbored multiple aneurysms). Three
      of the four patients were women. Two of the patients were siblings. The estimated
      prevalence in first-degree relatives was 4.2% (95% confidence interval 1.2-10.1).
      Of note, the mean age in the current study population was 39 years. The authors
      of recent metaanalyses have suggested that the prevalence of nonfamilial
      aneurysms is approximately 2%, despite earlier reports in which higher figures
      were cited. CONCLUSIONS: The authors conclude that first-degree relatives of
      patients with aneurysms are at higher risk for harboring an intracranial
      aneurysm.

PMID- 15844875
TI  - Surgical management of unruptured basilar artery bifurcation aneurysms. Technical
      note.
AB  - The basilar artery (BA) bifurcation is the most common site for aneurysms arising
      from the posterior circulation. Their inhospitable location, nested within the
      narrow confines of the interpeduncular fossa anterior to the brainstem, coupled
      with the rich network of adjacent critical thalamoperforating arteries irrigating
      the midbrain and thalamus, pose difficult anatomical obstacles for the surgeon.
      The age old adage that the only cure for intracranial aneurysms remains exclusion
      from circulation before rupture still holds true. Although management of
      unruptured aneurysms in general is still controversial, unruptured aneurysms of
      the BA bifurcation can be treated surgically with acceptable rates of morbidity.
      The clinician must gather and weigh all clinical, pathological, and radiological
      data when formulating recommendations for the individual patient. In the present
      report the authors describe their current technique for the surgical management
      of unruptured BA bifurcation aneurysms; this represents the culmination of the
      senior author's (N.K.) experience in the management of both ruptured and
      unruptured BA bifurcation aneurysms. A modified, right-sided subtemporal
      transtentorial approach has been adopted in all cases of isolated unruptured BA
      bifurcation aneurysms. Technical nuances are described.

PMID- 15844876
TI  - Intracranial ependymoma.
AB  - OBJECT: An intracranial ependymoma is a relatively rare but very interesting
      variety of glioma. In this paper, the authors compiled a review of the
      pathological features, imaging characteristics, and treatment strategies related
      to this brain tumor. METHODS: A Medline search was conducted using the term
      "ependymoma." The bibliographies of papers obtained were also checked for
      articles and chapters that could provide additional understanding of this tumor.
      Malignant ependymomas and ependymomas of the spinal cord (including myxopapillary
      ependymomas) were excluded from this review. CONCLUSIONS: The posterior fossa is
      the most frequent site for an intracranial ependymoma. Children are frequently
      affected. Most authors recommend resecting as much of the tumor as is safely
      possible. Microscopically, ependymal tumors show both epithelial and glial
      features. Glial fibrillary acidic protein immunohistochemistry, therefore, helps
      in identifying ependymomas. Because ependymomas often recur despite surgical
      intervention, radiotherapy and/or radiosurgery may also play an important role in
      their treatment. The use of chemotherapy in the treatment of these tumors,
      especially in the very young, is still being studied.

PMID- 15844877
TI  - Tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in
      established and primary glioma cell lines.
AB  - OBJECT: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is
      a member of the TNF cytokine family, which mediates programmed cell death
      (apoptosis) selectively in tumor cells. The selective tumoricidal activity of
      TRAIL is believed to be modulated by agonistic (DR4 and DR5) and antagonistic
      receptors (DcR1 and DcR2), which appear to compete for ligand binding. Because
      TRAIL is expressed in a wide range of tissues, including brain, kidney, and
      spleen, and seems consistently to induce cell death in tumor cells, the cytokine
      has been identified as a promising approach for selectively inducing tumor cell
      death. In this study, the authors examine the importance of TRAIL's receptors in
      both its selectivity for tumor cells and its ability to induce apoptosis.
      METHODS: The authors first examined sensitivity to TRAIL and expression of TRAIL
      receptors in four established and four primary cultured glioma cell lines by
      using viability and fluorescent apoptosis assays. They then evaluated DR5
      expression and JNK, caspase 3, and caspase 7 activation by conducting immunoblot
      analyses. Reverse transcriptase-polymerase chain reaction (RTPCR) was performed
      to study expression of DR4, DR5, DcR1, and DcR2. The DR5 transcripts from one
      TRAIL-sensitive, one partially TRAIL-resistant, and one TRAIL-resistant cell line
      were subsequently sequenced. The expression of TRAIL receptors in normal and
      glial brain tumor pathological specimens were then compared using
      immunohistochemistry. Finally, to study the direct effects of DR5 on glioma
      cells, the authors conducted transient and stable transfections of the full
      length DR5 transcript into glioma cells with and without preestablished
      overexpression of the antiapoptotic gene bcl-2. The established glioma cell lines
      T98G and U87MG, and all primary cell lines, were apoptotic at greater than or
      equal to 100 ng/ml TRAIL. The A172 cells, by contrast, were susceptible only with
      cycloheximide, whereas U373MG cells were not susceptible to TRAIL. The JNK,
      caspase 3, and caspase 7 activity evaluated after treatment with TRAIL showed
      that TRAIL-sensitive cell lines exhibited downstream caspase activation, whereas
      TRAIL-resistant cells did not. The DR5 sequences in T98G, A172, and U373MG cell
      lines were identical to published sequences despite these differences in
      sensitivity to TRAIL. The RT-PCR performed on extracts from the eight glioma cell
      lines showed that all expressed DR5. Immunohistochemistry revealed ubiquitous
      expression of DR5 in glioma specimens, with an associated lack of decoy receptor
      expression. Normal brain specimens, by contrast, stained positive for both DR5
      and DcR1. Overexpression of DR5 under both transfection conditions resulted in
      cell death in all three cell lines. The previously seen resistance of U373 cells
      to TRAIL was not observed. Apoptotic cell death was confirmed using DNA
      fragmentation in T98G cell lines and fluorescent miscroscopy in all cell lines.
      The T98G cells stably transfected with bcl-2 before DR5 overexpression were
      protected from cell death. CONCLUSIONS: The authors conclude that DR5 represents
      a promising new approach to directly activating the intrinsic caspase pathway in
      glioma cells. The fact that TRAIL-resistant gliomas do not express decoy
      receptors suggests a mechanism of resistance unique from that proposed for normal
      tissues. The overexpression of DR5 induced apoptotic cell death in glioma cells
      without TRAIL and was able to overcome the resistance to TRAIL demonstrated in
      U373 cells. The Bcl-2 protects cells from DR5 by acting downstream of the
      receptor, most likely at the level of caspase activation.

PMID- 15844878
TI  - A unique highly oxygenated pyrano[4,3-c][2]benzopyran-1,6-dione derivative with
      antioxidant and cytotoxic activities from the fungus Phellinus igniarius.
AB  - [structure: see text] A unique pyrano[4,3-c][2]benzopyran-1,6-dione derivative
      with an unprecedented carbon skeleton, phelligridin G (1), has been isolated from
      the fruiting body of the fungus Phellinus igniarius. Its structure was elucidated
      by detailed spectroscopic analysis. A possible biogenetic origin of 1 mediated by
      the fungal metabolite precursor 4-hydroxy-6-methyl-2-pyrone was postulated.
      Phelligridin G (1) showed antioxidant activity inhibiting rat liver microsomal
      lipid peroxidation and moderate selective cytotoxic activities against human
      cancer cell lines.

PMID- 15844880
TI  - Sequence-specific binding of m-phenylene ethynylene foldamers to a piperazinium
      dihydrochloride salt.
AB  - [reaction: see text] Binding properties of a series of isomeric m-phenylene
      ethynylene oligomers containing short amide sequences to a piperazinium
      dihydrochloride salt were investigated by using circular dichroism (CD)
      measurements. Although these isomeric oligomers exhibited similar helical
      conformations, high affinity was observed only for one oligomer. This behavior is
      presumably controlled by the orientation of amino groups of the amide sequence
      and the folded conformation of the oligomer.

PMID- 15844879
TI  - Highly regioselective Diels-Alder reactions toward oroidin alkaloids: use of a
      tosylvinyl moiety as a nitrogen masking group with adjustable electronics.
AB  - [reaction: see text] The use of the p-toluenesulfonyl (Ts) and tosylvinyl (Tsv)
      groups as nitrogen masking groups imparted high regioselectivity in Diels-Alder
      reactions directed toward members of the oroidin-derived marine alkaloid family.
      The electron-withdrawing Tsv group was utilized as an electronically adjustable
      nitrogen-protecting group as subsequent hydrogenation provided the more electron
      rich tosylethyl (Tse) group. This electronic adjustment strategy avoided a
      protecting group exchange and provided the required electronics for the key
      chlorination/ring-contraction sequence.

PMID- 15844881
TI  - Studies into the stereoselectivity of tartrate-derived dienophiles.
AB  - [reaction: see text] Diels-Alder reactions of 1-(tert-butyldimethylsiloxy)-1,3
      butadiene (3) with three C2 symmetric dienophiles derived from tartaric acid have
      been examined. Complementary diastereoselectivity is observed depending on the
      nature of the 1,2-diol protecting group incorporated in these dienophiles.

PMID- 15844882
TI  - C(60)-exTTF-C(60) Dumbbells: cooperative effects stemming from two C(60)s on the
      radical ion pair stabilization.
AB  - [structure: see text] The presence of a second C(60) cage in C(60)-exTTF-C(60)
      triads [exTTF = 9,10-bis(1,3-dithiol-2-ylidene)-9,10-anthraquinone] has
      beneficial effects on the stabilization of the radical ion pair formed upon
      irradiation in comparison with the related C(60)-exTTF dyad. Although C(60)-exTTF
      C(60) ensembles show no electronic interaction between the electroactive units in
      the ground state, their irradiation leads to C(60)(*)(-)-exTTF(*)(+)-C(60)
      species with lifetimes on the order of 600 ns in benzonitrile; these lifetimes
      are twice those determined for the analogous C(60)-exTTF dyad.

PMID- 15844883
TI  - Increasing the kinase specificity of k252a by protein surface recognition.
AB  - [reaction: see text] Here we describe a miniature protein (1) that presents the
      cAMP-dependent protein kinase (PKA) recognition epitope found within the heat
      stable Protein Kinase Inhibitor protein (PKI) and a miniature protein conjugate
      (1-K252a) in which 1 is joined covalently to the high-affinity but nonselective
      kinase inhibitor K252a. Miniature protein 1 recognizes PKA with an affinity that
      rivals that of PKI and, in the context of 1-K252a, leads to a dramatic increase
      in kinase specificity.

PMID- 15844884
TI  - Membrane receptor probes: solid-phase synthesis of biotin-Asp-PEG-arvanil
      derivatives.
AB  - [structure: see text] A modular, flexible solid-phase synthetic route for the
      preparation of biotinylated cross-linking probes of membrane receptors is
      described. The route utilizes an orthogonal protection strategy employing a Pd[0]
      cleavable allyl linker attached to the probe via an aspartate residue. The
      versatility of the method is illustrated through the synthesis of a number of
      arvanil-derived cannabinoid receptor ligands displaying either a photoaffinity or
      a chemical cross-linking group.

PMID- 15844885
TI  - Side-chain-anchored N(alpha)-Fmoc-Tyr-OPfp for bidirectional solid-phase
      synthesis.
AB  - [reaction: see text] A mild resin-immobilization strategy employing a readily
      prepared trityl bromide resin for anchoring building blocks via a phenol group
      has been developed. With N(alpha)-Fmoc-Tyr-OPfp as a starter building block, it
      was possible to prepare asymmetrically substituted hybrids of spider- and wasp
      type polyamine toxins using solid-phase peptide synthesis conditions.

PMID- 15844886
TI  - Highly regio- and stereoselective synthesis of 2(E),4-Alkadienoates via the Pd(0)
      catalyzed reaction of aryl halides with 3,4-alkadienoates.
AB  - [reaction: see text] 2(E),4-Alkadienoates were prepared highly stereoselectively
      via the Pd(0)/Ag(2)CO(3)-cocatalyzed reaction of 3,4-alkadienoates and aryl
      halides. The reaction is believed to proceed via the oxidative addition
      carbopalladation-beta-H elimination process. Compared to the other reported
      methods for the synthesis of 2,4-alkadienoates, in which usually only
      disubstituted C=C bonds were formed, the current reaction forms the
      trisubstituted or even tetrasubstituted C=C bond highly stereoselectively.

PMID- 15844887
TI  - Iridium complex-catalyzed reaction of 1,6-enynes: cycloaddition and
      cycloisomerization.
AB  - [reaction: see text] 1,6-Enynes reacted with monoynes to give cyclohexadiene
      derivatives in the presence of a catalytic amount of [Ir(cod)Cl](2)/ligand. DPPE
      was most suitable for cycloaddition. Diastereoselective cycloaddition was also
      possible. In the absence of monoynes, 1,6-enynes cycloisomerized to (Z)-1
      alkylidene-2-methylenecyclopentane derivatives. DPPF was most suitable for
      cycloisomerization. These results are the first examples of highly Z-selective
      cycloisomerization.

PMID- 15844888
TI  - Highly stereoselective additions of tin enolates to nitroalkenes and subsequent
      conversion of the nitro group into a nitrile.
AB  - [reaction: see text] Sn-chelated glycine ester enolates are efficient
      nucleophiles for highly stereoselective 1,4-additions toward nitroolefins and
      subsequent reductions of the nitronate intermediates formed, giving rise to amino
      acid nitriles.

PMID- 15844889
TI  - DTPA-bisamide-based MR sensor agents for peroxidase imaging.
AB  - [reaction: see text] The synthesis and some properties of two novel DTPA
      bisamides are reported. These derivatives were designed as enzyme-activated
      contrast agents (CA) for magnetic resonance imaging. Both derivatives bear
      tyramido or 5-hydroxytryptamido groups that could be oligomerized in situ in the
      presence of peroxidase/H(2)O(2) pair resulting in a net increase in longitudinal
      (R1) relaxivity.

PMID- 15844891
TI  - Rhodium-catalyzed intramolecular conjugate addition of vinylstannanes to 2,3
      dihydro-4-pyridones. An efficient route to stereoselective construction of
      indolizidines.
AB  - [reaction: see text] [RhCl(cod)](2) is an effective catalyst for the
      intramolecular conjugate addition of vinylstannanes to 2,3-dihydro-4-pyridones
      under neutral conditions at room temperature. The reaction occurs in good yields,
      giving indolizidine skeletons with excellent diastereoselectivity. A
      stereochemical outcome observed in these cyclizations is proposed.

PMID- 15844890
TI  - A novel and efficient method for cleavage of phenacylesters by magnesium
      reduction with acetic acid.
AB  - [reaction: see text] In the present study, we use magnesium turnings as a new
      deprotection reagent for the phenacyl group during orthogonal organic synthesis
      in the presence of other esters and sensitive protecting groups. By applying the
      new magnesium turnings/acetic acid deprotection method, phenacyl group can be
      more easily combined with other protecting groups that are not compatible with
      the zinc/acetic acid method.

PMID- 15844892
TI  - Catalytic asymmetric synthesis of hydroxy enol ethers: approach to a two-carbon
      homologation of aldehydes.
AB  - [reaction: see text] Hydroboration of ethoxy acetylene, transmetalation to zinc,
      and addition to aldehydes in the presence of a chiral amino alcohol ligand (MIB)
      affords hydroxy enol ethers with high ee. The resultant enantiomerically enriched
      hydroxy enol ethers were converted to protected hydroxy aldehydes, a useful
      synthetic building block for the construction of a variety of polyoxygenated
      natural products. In addition, diastereoselective formation of syn- and anti-1,3
      diols was studied.

PMID- 15844893
TI  - Catalytic enantioselective sulfinyl transfer using cinchona alkaloid catalysts.
AB  - [reaction: see text] Practical reaction conditions for the catalytic
      enantioselective synthesis of sulfinate esters are reported. Commercially
      available cinchona alkaloids were found to be superior catalysts for the sulfinyl
      transfer reaction of tert-butanesulfinyl chloride and a variety of benzyl
      alcohols. Sulfinyl transfer with 2,4,6-trichlorobenzyl alcohol and 10 mol % of
      the commercially available, inexpensive catalyst quinidine provided the pure
      sulfinate ester product in 92% isolated yield and with 90% ee.

PMID- 15844894
TI  - Enantioselective intramolecular alkene hydroaminations catalyzed by yttrium
      complexes of axially chiral bis(thiolate) ligands.
AB  - [structure: see text] A yttrium(III) complex derived from proligand 7c has been
      shown to be a superior catalyst for enantioselective intramolecular alkene
      hydroaminations that provide cyclic amines with ee's ranging from 69% to 89%.

PMID- 15844895
TI  - Biotin-amino acid conjugates: an approach toward self-assembled hydrogelation.
AB  - [structure: see text] Amino acid-appended biotin hydrogelators are a new class of
      low-molecular-weight gelators that display remarkable gelation properties in
      aqueous media, including buffer solutions with variable pH.

PMID- 15844896
TI  - Solvent-dependent chemoselectivity in ruthenium-catalyzed cyclization of
      iodoalkyne-epoxide functionalities.
AB  - [reaction: see text] Treatment of 1-(2'-iodoethynylphenyl)-2-propyloxirane (3)
      with TpRuPPh(3)(CH(3)CN)(2)PF(6) catalyst (10 mol %) produced 1-iodo-2-naphthol
      (3a) exclusively in DMF, but gave 2-iodobenzo[d]oxepin (3b) efficiently in
      benzene. Such a solvent-dependent chemoselectivity suggests a solution
      equilibrium between ruthenium-pi-iodoalkyne and ruthenium-2-iodovinylidene
      intermediates.

PMID- 15844897
TI  - Simple approach to "locked" chlorins.
AB  - [reaction: see text] A novel synthetic approach to diversely functionalized
      "locked" chlorins is described. A suitably substituted 2,5-diformylpyrrole
      undergoes the macrocyclization reaction with tripyrranes, thereby generating
      porphyrins. Upon the reaction with 1,3-dipoles these porphyrins regioselectively
      furnish pyrrolidine-fused chlorins, which cannot oxidize to the corresponding
      porphyrins. In the process involving just six steps from commercially available
      and cheap materials we are able to obtain approximately 200 mg of pure stable
      chlorins (the overall yield is 1.5-2.8%).

PMID- 15844898
TI  - Facile and convenient syntheses of 6,11-dihydro-5H-indeno[1,2-c]isoquinolin- 5
      ones and 6,11-dihydro-5H-indolo[3,2-c]isoquinolin-5-one.
AB  - [reaction: see text] The synthesis of 6,11-dihydro-5H-indeno[1,2-c]isoquinolin-5
      ones from the base-promoted condensation reaction of homophthalic anhydride and 2
      (bromomethyl)-benzonitrile and a convenient method for the synthesis of
      indolo[3,2-c]isoquinolinones are described.

PMID- 15844899
TI  - Applications of ruthenium hydride borohydride complexes containing phosphinite
      and diamine ligands to asymmetric catalytic reactions.
AB  - [reaction: see text] A series of novel trans-ruthenium hydride borohydride
      complexes with chiral phosphinite and diamine ligands were synthesized. They can
      be used in the asymmetric transfer hydrogenation of aryl ketones, including base
      sensitive ones, to give chiral alcohols in moderate to good enantioselectivities
      (up to 94% ee). They are also efficient catalysts for the Michael addition of
      malonates to enones with enantioselectivities of up to 90%. This kind of catalyst
      allows a one-pot tandem Michael addition/H(2) hydrogenation protocol to build
      structures with multiple chiral centers.

PMID- 15844900
TI  - Arylamide dendrimers with flexible linkers via haloacyl halide method.
AB  - [reaction: see text] Soluble arylamide dendrons with flexible linkers, peripheral
      ester or carboxyl groups (R), and focal amino or halogen functionalities (F) were
      synthesized from aryl glycineamide (AG) building blocks. The AG blocks were
      prepared in high yields from trivial starting materials by Fischer's haloacyl
      halide method, which also could be extended to the dendrimer synthesis itself.
      The G2 AG dendrons were coupled to a Pd porphyrin core, demonstrating outstanding
      encapsulation efficiency in aqueous solutions.

PMID- 15844901
TI  - Structures, biological activities, and total syntheses of 13-hydroxy- and 13
      acetoxy-14-nordehydrocacalohastine, novel modified furanoeremophilane-type
      sesquiterpenes from Trichilia cuneata.
AB  - [reaction: see text] 13-Hydroxy-14-nordehydrocacalohastine (2) and 13-acetoxy-14
      nordehydrocacalohastine (3), two novel modified furanoeremophilane-type
      sesquiterpenes isolated from Trichilia cuneata, showed inhibitory activities for
      membrane lipid peroxidation in mitochondria and microsomes. The first, highly
      convergent total syntheses of new compounds 2 and 3 have also been achieved via a
      palladium-mediated three-component coupling reaction between 2-iodotoluene (7), 1
      penten-4-yn-3-ol (8), and diethyl ethoxymethylenemalonate (9).

PMID- 15844902
TI  - 5-Endo-dig electrophilic cyclization of 1,4-disubstituted but-3-yn-1-ones:
      regiocontrolled synthesis of 2,5-disubstituted 3-bromo- and 3-iodofurans.
AB  - [reaction: see text] 5-Endo-dig electrophilic cyclization of 1,4-diaryl but-3-yn
      1-ones with N-bromosuccinimide or N-iodosuccinimide/acetone and iodine
      monochloride/CH(2)Cl(2), at room temperature, in the absence of base, provides 3
      halo-2,5-diarylfurans with excellent regiocontrol and high yields (81-94%).

PMID- 15844903
TI  - An enantioselective NMR shift reagent for cationic aromatics.
AB  - [structure: see text] The water-soluble tetra l-prolinylmethyl derivative of a
      tetrasulfonated calix[4]resorcarene is an effective chiral NMR solvating agent
      for compounds with bicyclic aromatic or indole rings. Complexation of bicyclic
      substrates with the calix[4]resorcarene is likely promoted by hydrophobic
      effects. The bicyclic substrates have larger association constants with the
      calix[4]resorcarene than similar phenyl-containing compounds. Substantial
      enantiomeric discrimination is observed for several resonances in the (1)H NMR
      spectra of these substrates.

PMID- 15844904
TI  - An acid-stable tert-butyldiarylsilyl (TBDAS) linker for solid-phase organic
      synthesis.
AB  - [reaction: see text] A new, robust tert-butyldiarylsilyl (TBDAS) linker has been
      developed for solid-phase organic synthesis. This linker is stable to both protic
      and Lewis acidic reaction conditions, overcoming a significant limitation of
      previously reported silyl linkers. Solid-phase acetal deprotection, olefination,
      asymmetric allylation, and silyl protecting group deblocking reactions have been
      demonstrated with TBDAS-linked substrates.

PMID- 15844905
TI  - Palladium-catalyzed intermolecular three-component coupling of aryl iodides,
      alkynes, and alkenes to produce 1,3-butadiene derivatives.
AB  - [reaction: see text] The sequential three-component coupling of aryl iodides,
      diarylacetylenes, and monosubstituted alkenes effectively proceeds in the
      presence of Pd(OAc)(2), LiCl, and NaHCO(3) as catalyst, promoter, and base,
      respectively, in DMF-H(2)O to produce the corresponding 1,3-butadiene
      derivatives.

PMID- 15844907
TI  - Extension of N-confused porphyrin by an o-xylene fragment.
AB  - [reaction: see text] A simple method of modification of N-confused porphyrin is
      provided by reactions of 5,10,15,20-tetraaryl-2-aza-21-carbaporphyrin with
      alpha,alpha'-dibromoxylene. The N-bromoxylene-substituted monomer formed in a
      first step of alkylation can be converted to the products with the extended
      structure on the N-confused pyrrole for which formation of organometallic
      silver(III) complexes has been shown.

PMID- 15844906
TI  - Regioselectivity of rhodium nitrene insertion. Syntheses of protected glycals of
      l-daunosamine, d-saccharosamine, and l-ristosamine.
AB  - [reaction: see text] The carbamate-protected glycals of naturally occurring 3,4
      cis-3-amino-2,3,6-trideoxyhexoses (l-daunosamine, d-saccharosamine, and l
      ristosamine) were prepared from noncarbohydrate starting materials. The short,
      high-yield syntheses are based on the chemoselective insertion of a rhodium
      nitrene in an allylic C-H bond rather than in a C-H bond that is alpha to an
      oxygen substituent.

PMID- 15844908
TI  - An efficient and simple aminobenzannulation reaction: pyrrolidine as a trigger
      for the synthesis of 1-amino-acridines.
AB  - [reaction: see text] A new aminobenzannulation methodology has been developed and
      applied successfully to the synthesis of 1-amino-acridines. The key and last step
      goes through an enamine intermediate that was detected in some cases. When
      pyrrolidine and powdered 4 A molecular sieves were used, the enamine synthesis
      and the aminobenzannulation step took place subsequently, whereas for other
      secondary amines, neutral Al(2)O(3) or PtCl(2) catalysis was necessary.

PMID- 15844909
TI  - Spontaneous racemization and epimerization behavior in solution of chiral
      nitroxides.
AB  - [reaction: see text] Enantiomerically enriched samples of chiral cyclic
      nitroxides with a 4-hydroxyphenyl group on the stereogenic center bearing the NO
      radical group undergo unprecedented spontaneous racemization and/or epimerization
      in aprotic solvents, which can be well accounted for by the multistep
      equilibrations involving planar quinoid intermediates.

PMID- 15844910
TI  - Hydrazulene ring systems via heteroatom-assisted [1,2]-shift of oxonium and
      sulfonium ylides.
AB  - [reaction: see text] Cyclic mixed acetals with pendant diazoketone side chains
      undergo rearrangement to ether-bridged cycloheptane ring systems on treatment
      with Cu(hfacac)(2). Stevens [1,2]-shift of an oxonium ylide furnishes the major
      product (7), in some cases accompanied by minor amounts of a product (8)
      resulting from [1,2]-shift of a sulfonium ylide. In the subsequent sulfur
      triggered cleavage of the bridging ether, the desired bicyclo[5.3.0]heptene was
      obtained, along with the product of novel S(N)2' attack on the resulting allylic
      ketal.

PMID- 15844911
TI  - Synthesis of alpha,beta-unsaturated 4,5-disubstituted gamma-lactones via ring
      closing metathesis catalyzed by the first-generation Grubbs' catalyst.
AB  - [reaction: see text] 4-Methyl-5-alkyl-2(5H)-furanones have been prepared by
      ruthenium-catalyzed ring-closing metathesis of the suitable methallyl acrylates.
      Despite the electron deficiency of the conjugated double bond and of the gem
      disubstitution of the allylic alkene moiety in the starting acrylates, the first
      generation Grubbs' catalyst I proved to be an effective promoter for the ring
      closure, affording the expected butenolides in good to high yields.

PMID- 15844912
TI  - Formation of disubstituted beta-lactones using bifunctional catalysis.
AB  - [reaction: see text] Acid chlorides and aromatic aldehydes react in the presence
      of a stoichiometric amount of a tertiary amine and catalytic amounts of a
      cinchona alkaloid derivative and a Lewis acid to produce beta-lactones in high
      diastereo- and enantioselectivity. The sense of the diastereoselectivity depends
      on the substitution of the acid chloride, with the reactions of aliphatic acid
      chlorides giving predominantly the trans-isomer and those of alkoxyacetyl
      chlorides favoring formation of the cis-isomer.

PMID- 15844913
TI  - Pectenotoxin-2 synthetic studies. 2. Construction and conjoining of ABC and DE
      Eastern hemisphere subtargets.
AB  - [reaction: see text] Practical asymmetric synthesis of aldehyde 2 and tetrazolyl
      sulfone 3 has allowed for their coupling via Julia olefination to generate 32 as
      a single product. This substance possesses the entire carbon backbone of the A-E
      substructure of pectenotoxin-2.

PMID- 15844914
TI  - Preferential axial protonation in a zwitterionic calix[4]arene.
AB  - [structure: see text] Calixarene 3, substituted at two methylene bridges by
      dimethylamino groups, exists in the crystal and in polar solvents as a
      zwitterion, with the axial dimethylamino group protonated.

PMID- 15844915
TI  - Ab initio study of the S(N)2 and E2 mechanisms in the reaction between the
      cyanide ion and ethyl chloride in dimethyl sulfoxide solution.
AB  - [reaction: see text] Reliable theoretical calculations predict a free energy
      barrier for nitrile formation from the reaction between the cyanide ion and ethyl
      chloride in DMSO solvent of 24.1 kcal/mol, close to the experimental value of
      22.6 kcal/mol. We have also predicted that the isonitrile formation is less
      favorable by 4.7 kcal/mol, while the elimination mechanism is less favorable by
      more than 10 kcal/mol. These results indicate that isonitrile formation and
      bimolecular elimination are not significant side reactions for primary alkyl
      chloride reactions.

PMID- 15844916
TI  - Total synthesis of (+)-discodermolide: a highly convergent fourth-generation
      approach.
AB  - [structure: see text] A highly convergent, fourth-generation total synthesis of
      (+)-discodermolide (1), with a longest linear sequence of 17 steps and an overall
      yield of 9.0%, has been achieved. Highlighting the strategy is the efficient
      construction and sequential, bidirectional union of a linchpin comprising the
      C(9)-C(14) Wittig salt-vinyl iodide (-)-18. Importantly, Wittig salt generation
      proceeded in excellent yield under ambient pressure.

PMID- 15844917
TI  - Simple (imidazol-2-ylidene)-Pd-acetate complexes as effective precatalysts for
      sterically hindered Suzuki-Miyaura couplings.
AB  - [reaction: see text] A simplified synthesis of N-heterocyclic carbene (NHC)Pd
      carboxylate complexes and their activity in Suzuki-Miyaura cross-coupling
      reactions are described. Coupling of sterically hindered aryl and activated alkyl
      chlorides bearing beta-hydrogens has been successfully achieved.

PMID- 15844918
TI  - Synthesis of purines and other fused imidazoles from acyclic amidines and
      guanidines.
AB  - [reaction: see text] Purines, xanthines, and other fused imidazoles can be
      prepared from amidines or guanidines, with retrosynthetic disconnection at the
      ring fusion. Ring closure proceeds using Cu(I), with no special ligands required.
      The method allows for easy modification of the heterocyclic nucleus and is
      tolerant of functionality pendant to the ring system.

PMID- 15844920
TI  - A fluorous chiral dirhodium(II) complex as a recyclable asymmetric catalyst.
AB  - [reaction: see text] The chiral fluorous complex tetrakis-dirhodium(II)-(S)-N-(n
      perfluorooctylsulfonyl)prolinate has been prepared and used as a catalyst in
      homogeneous or fluorous biphasic fashion. The catalyst displays good chemo- and
      enantioselectivity in intermolecular cyclopropanation and C-H bond activation
      reactions. The catalyst can be simply and thoroughly separated from the reaction
      mixture and is recyclable.

PMID- 15844919
TI  - Stereochemical diversity in chiral ligand design: discovery and optimization of
      catalysts for the enantioselective addition of allylic halides to aldehydes.
AB  - [reaction: see text] We have identified a new set of stereochemically diverse
      oxazoline ligands derived from simple amino acids that promote the Cr-catalyzed
      enantioselective addition of allylic halides to aldehydes in up to 95% ee. The Cr
      catalyzed allylation using ligand 1d is rather insensitive to the nature of the
      allylic bromide (crotyl, allyl, and methallyl) in that >90% ee is observed for
      all three bromides evaluated in the addition to benzaldehyde.

PMID- 15844921
TI  - Reductive cross-aldol reaction using bromoaldehyde and an aldehyde mediated by
      germanium(II): one-pot, large-scale protocol.
AB  - [reaction: see text] The reaction of alpha-bromoaldehyde with aldehyde in the
      presence of GeCl(2)-dioxane gave the syn-selective cross-aldol equivalent. A
      catalytic amount of Bu(4)NBr improved the yield and selectivity. The initially
      formed aldol adduct (beta-germoxyaldehyde) did not suffer from over-reaction.
      This system enabled an intramolecular aldol reaction to give cyclic compounds
      effectively. One-pot synthetic methodology including bromination of aldehyde
      followed by cross-aldol reaction with the second aldehyde was successful on a
      large-scale.

PMID- 15844922
TI  - Asymmetric synthesis of the dibenzocyclooctadiene lignans interiotherin a and
      gomisin R.
AB  - [structure: see text] Asymmetric total syntheses of the dibenzocyclooctadiene
      lignans interiotherin A and angeloylgomisin R are reported. The syntheses were
      based on an atropdiastereoselective, copper-promoted biaryl coupling reaction, a
      diastereoselective hydroboration/Suzuki-Miyaura coupling reaction sequence, and
      an asymmetric boron-mediated tiglylation of an aryl aldehyde precursor.

PMID- 15844923
TI  - A C-glycosidation approach to the central core of amphidinol 3: synthesis of the
      c39-c52 fragment.
AB  - [reaction: see text] A concise route to an advance precursor (3) of the central
      core of amphidinol 3, a natural occurring polyketide, has been developed by
      applying a reductive lithiation as key step. The origin of the
      diastereoselectivity of this reaction was comprehensively studied for
      nucleophilic C-glycoside donor 5 and differently protected analogues.

PMID- 15844924
TI  - High-yielding intramolecular direct arylation reactions with aryl chlorides.
AB  - [reaction: see text] An N-heterocyclic carbene palladium catalyst system is used
      to promote direct arylation of a broad range of aryl chlorides to form six- and
      five-membered ring biaryls. An influence of the halide on the palladium
      precatalyst on catalyst activation has been revealed, as has a beneficial effect
      of NHC salts that allows the turnover numbers to be increased by simple addition
      of imidazolium salts to the reaction mixture.

PMID- 15844925
TI  - Perchloro-2,5,8-triazaphenalenyl radical.
AB  - [reaction: see text] The unusually stable perchloro-2,5,8-triazaphenalenyl
      radical 1 and its twisted dechlorinated dimer 2 were synthesized and
      characterized by ESR spectroscopy and X-ray crystallography. The X-ray structure
      of dimer 2 shows that the double bond connecting the two triazaphenalene systems
      is strongly twisted. Dimer 2 has a dramatic color shift from the solid state to
      solution, which may be due to a change of the twisting angle between both states.

PMID- 15844926
TI  - Boron-directed regio- and stereoselective enyne cross metathesis: efficient
      synthesis of vinyl boronate containing 1,3-dienes.
AB  - [reaction: see text] Regio- and stereoselective enyne cross metathesis reactions
      between borylated alkynes and terminal alkenes were realized to provide a variety
      of functionalized vinyl boronates. High chemical yield and regioselectivity was
      achieved irrespective of substituents on the alkyne and alkene counterparts,
      whereas Z/E-selectivity was found to be dependent upon the substituents both on
      the alkyne and alkene.

PMID- 15844927
TI  - Versatile dehydrogenative alcohol silylation catalyzed by Cu(I)-phosphine
      complex.
AB  - [reaction: see text] Cu(I) complexes of xanthane-based diphosphines were
      versatile catalysts for dehydrogenative alcohol silylation, exhibiting high
      activity and broad substrate scope. Highly selective silylation of 1-decanol over
      2-decanol is possible even with a silylating reagent of small steric demand such
      as HSiMe(2)Ph or HSiEt(3).

PMID- 15844928
TI  - Synthesis of the spirofungin B core by a reductive cyclization strategy.
AB  - [reaction: see text] A reductive decyanation approach to the synthesis of the
      core of spirofungin B has been developed. Spirofungin B has only one anomeric
      stabilization in the spiroacetal and was isolated along with its spiroacetal
      epimer, spirofungin A. The cyclization precursor was constructed from readily
      available starting materials. The reductive cyclization reaction was both
      efficient and stereoselective. The reductive cyclization strategy to spiroacetals
      is convergent and effective.

PMID- 15844929
TI  - Intricarene, an unprecedented trispiropentacyclic diterpene from the Caribbean
      Sea plume Pseudopterogorgia kallos.
AB  - [structure: see text] A novel trispiropentacyclic diterpene, intricarene (1), was
      isolated from the hexane extract of the Caribbean gorgonian octocoral
      Pseudopterogorgia kallos. Its highly entangled structure was established by
      interpretation of NMR, IR, UV, and HREIMS data and subsequently confirmed by X
      ray diffraction analysis. The unprecedented carbon skeleton of 1 constitutes a
      new addition to the already impressive architectural diversity of the diterpene
      class of marine secondary metabolites.

PMID- 15844930
TI  - Stereospecific synthesis of dienones via a torquoselective retro-Nazarov
      reaction.
AB  - [reaction: see text] Enol ethers are cleaved via a three-step sequence involving
      cycloaddition with dichloroketene, ring expansion with diazomethane, and a base
      mediated retro-Nazarov reaction. The latter conrotatory process proceeds
      torquoselectively and stereospecifically in accord with theoretical predictions.

PMID- 15844933
TI  - Photochemical relationships in Sacoglossan polypropionates.
AB  - Cyercene A has been synthesized and converted to placidene A and isoplacidene A
      through photoisomerization with sunlight. Hydroperoxide, isolated form Placida
      dendritica, was synthesized both by singlet oxygenation of cyercene A using Rose
      Bengal and through the irradiation of cyercene A alone in aerobic solution. The
      observation that hydroperoxide could be made by singlet oxygenation of cyercene A
      and that this occurs when cyercene A alone is irradiated supported the hypothesis
      that gamma-pyrones may act as triplet sensitizers. This was confirmed using
      cyercene A and a model gamma-pyrone to sensitize the photooxidation of n-butyl
      sulfide. The biosynthetic implications of these observations for Sacoglossan
      polypropionates are discussed.

PMID- 15844934
TI  - Ipomoeassins A-E, cytotoxic macrocyclic glycoresins from the leaves of Ipomoea
      squamosa from the Suriname rainforest.
AB  - The new glycoresins, ipomoeassins A-E (1-5), have been isolated from the leaves
      of Ipomoea squamosa. The structures were elucidated by spectroscopic analyses and
      chemical transformations. The absolute configurations of C-5 (ipomoeassins 3-5)
      and C-11 (ipomoeassins 1 and 2) were determined by their derivatives with (R)-
      and (S)-MPA. All the isolates were active in the A2780 human ovarian cancer cell
      line assay, and 4 showed the highest activity with an IC(50) value of 35 nM.

PMID- 15844935
TI  - Microbial genomics as a guide to drug discovery and structural elucidation: ECO
      02301, a novel antifungal agent, as an example.
AB  - Analysis of the genome of Streptomyces aizunensis NRRL B-11277 indicated its
      potential to produce a compound of novel and highly predictable structure. The
      structure was predicted with sufficient accuracy to allow straightforward
      detection of the specific metabolite in HPLC profiles of fermentation extracts
      and hence to guide the isolation. The spectroscopic work was reduced to a
      confirmation of structure rather than a first principle determination. The
      compound, ECO-02301 (1), demonstrated potent antifungal activity. This work
      exemplifies not only the discovery of novel antibiotics from well-characterized
      organisms but also the utility of genomics as a further tool, complementary to
      spectroscopy, to enable rapid determination of complex structures.

PMID- 15844936
TI  - Taxoids and abietanes from callus cultures of Taxus cuspidata.
AB  - Seventeen known taxoids and 10 abietanes were isolated from the dark brown callus
      culture of Taxus cuspidata cultivated on a modified Gamborg's B5 medium with 0.5
      or 1.0 mg/L NAA. Seven known taxoids and four abietanes were obtained from the
      callus culture incubated under light irradiation on the medium with 1.0 mg/L NAA.
      Eight taxoids and five abietanes were also separated from the callus culture on
      the medium with 10 mmol/L beta-cyclodextrin and 1.0 mg/L NAA. The new compounds
      were identified by analyses of the spectroscopic data and were found to be abieta
      6,8,11,13-tetraene-3beta,12-diol (1), 3beta,20-epoxy-12-methoxy-abieta-8,11,13
      triene-3alpha,11-diol (2), 3alpha-hydroxy-9(10-->20)abeo-abieta-1,5,8,10(20),13
      pentaene-7,11,12-trione (3), 2-hydroxy-9(10-->20)abeo-abieta-1,5,8,10(20),13
      pentaene-3,7,11,12-tetraone (4), and 3,7-dioxo-9(10-->20)abeo-12-norabieta
      1,5,8,10(20),13-pentaene-11,13-lactone (5), respectively. The yield of paclitaxel
      and its analogues was markedly decreased in the calluses mentioned above compared
      with that of standard callus. Instead, abietanes and some taxoids related to
      biosynthesis of paclitaxel were produced. Taxusin (6) exhibited stronger MDR
      reversing activity than verapamil toward 2780 AD tumor cells.

PMID- 15844937
TI  - Cyclobutane dimers from the Colombian medicinal plant Achyrocline bogotensis.
AB  - Five cyclobutane dimers, achyrodimers A-E (1-5), along with 11 known compounds
      were isolated from the methanol extract of the Colombian medicinal plant
      Achyrocline bogotensis. Their structures were elucidated by spectroscopy. Several
      of these compounds were screened for cytokine-inducing activity in human
      peripheral blood mononuclear cells.

PMID- 15844938
TI  - Makaluvic acids from the South African latrunculid sponge Strongylodesma
      aliwaliensis.
AB  - Two new metabolites, makaluvic acid C (1) and N-1-beta-d-ribofuranosylmakaluvic
      acid C (2), were isolated from the recently described sponge Strongylodesma
      aliwaliensis collected off the east coast of South Africa. Standard spectroscopic
      techniques provided the structures of both compounds. Chiral GC analysis of the
      peracetylated aldononitrile derivative of the acid hydrolysate of 2 confirmed the
      d-configuration of the ribose moiety in this compound. Compound 2 and four
      related pyrroloquinoline metabolites, isolated previously from S. aliwaliensis,
      exhibited in vitro cytotoxicity against esophageal cancer cells.

PMID- 15844939
TI  - Isolation and structure elucidation of feeding deterrent diterpenoids from the
      sea pansy, Renilla reniformis.
AB  - Four new briarane diterpenoids, renillins A-D (1-4), and the known compound
      renillafoulin C (5) were isolated from the sea pansy, Renilla reniformis. The
      structures and relative stereochemistry were elucidated by the interpretation of
      spectroscopic data. Using laboratory feeding assays, all compounds tested at
      natural concentrations significantly deterred feeding by the predatory lesser
      blue crab, Callinectes similis, while renillins C (3) and D (4) also deterred
      feeding by the predatory mummichog fish, Fundulus heteroclitus. Renillins A (1)
      and B (2) were found to possess an oxygenation pattern without precedent in this
      skeletal class.

PMID- 15844940
TI  - Antioxidant phenolic glycosides from Moricandia arvensis.
AB  - The new phenolic glycosides quercetin 3,4'-di-O-beta-d-glucopyranoside-7-O-alpha
      l-rhamnopyranoside (moricandin) (1), beta-d-glucopyranosyl 4-O-beta-d
      glucopyranosylcaffeate (2), methyl 3-O-beta-d-glucopyranosyl-5-hydroxycinnamate
      (3), and beta-d-glucopyranosyl 4-O-beta-d-glucopyranosylbenzoate (4), together
      with the previously known beta-d-glucopyranosyl 4-hydroxybenzoate (5), methyl 4-O
      beta-d-glucopyranosylcaffeate (6), 1-O-caffeoyl-beta-d-glucopyranoside (7), and 2
      phenylethyl-beta-d-glucopyranoside (8), were isolated from the flowers of
      Moricandia arvensis. Their structures were elucidated by extensive spectroscopic
      analysis and chemical methods. Compounds 1-8 were evaluated for antioxidant
      activity using DPPH, TEAC, and reducing power assays, where the caffeic acid
      derivative 7 and the quercetin triglycoside 2 proved to possess the most potent
      scavenging activity.

PMID- 15844941
TI  - Sesquiterpenoids from Pulicaria canariensis and their cytotoxic activities.
AB  - Thirteen new sesquiterpenes, pulicanadiene A (1), B (2), and C (3), pulicanone
      (4), pulicanol (5), pulicanarals A (6), B (7), and C (8), pulicanadienals A (9)
      and B (10), pulicanadienol (11), and pulioplopanones A (12) and B (13), and seven
      known compounds, stigmasterol, ergosterol peroxide, calenduladiol, 7,4'-di-O
      methyldihydrokaempferol, 5,7-dihydroxy-3,3',4'-trimethoxyflavone,
      dihydroquercetin 7,3'-dimethyl ether, and 6,15alpha-epoxy-1beta,4beta
      dihydroxyeudesmane, were isolated from Pulicaria canariensis. Compound 4a showed
      cytotoxicity on the human myeloid leukemia cell line HL-60. The cytotoxicity was
      caused by induction of apoptosis as determined by microscopy of nuclear changes,
      activation of caspases, and the cleavage of poly(ADP-ribose) polymerase-1.

PMID- 15844942
TI  - Trinervitene diterpenes from soldiers of two Nasutitermes species from French
      Guyana.
AB  - Methanolic extracts of soldiers of Nasutitermes guayanae and N. surinamensis have
      been shown to contain complex mixtures of diterpenes and monoterpenes. Eighteen
      diterpenes have been isolated and identified; twelve of them are previously known
      nasute termite diterpenes, while six are new trinervitene diterpenes.
      2alpha,9beta-Dihydroxy-3beta,8beta-oxido-1(15)-trinervitene has been isolated
      from N. guayanae, while 3alpha,14alpha-diacetoxy-2beta-hydroxy-1(15),8(19),9
      trinervitatriene, 14alpha-acetoxy-2beta,3alpha-dihydroxy-1(15),8(19),9
      trinervitatriene, 2beta,3alpha-diacetoxy-11beta,14alpha-dihydroxy-1(15),8(19)
      trinervitadiene, 9alpha,14alpha-diacetoxy-2beta,3alpha-dihydroxy-1(15),8(19)
      trinervitadiene, and 2beta,9alpha,14alpha-triacetoxy-3alpha-hydroxy-1(15),8(19)
      trinervitadiene have been isolated from N. surinamensis. Their structures were
      determined on the basis of their spectroscopic properties.

PMID- 15844943
TI  - Anti-babesial and anti-plasmodial compounds from Phyllanthus niruri.
AB  - Bioassay-guided fractionation of boiled aqueous extracts from the whole plant of
      Phyllanthus niruri led to the isolation of 1-O-galloyl-6-O-luteoyl-alpha-d
      glucose (1), with IC(50) values of 4.7 microg/mL against Babesia gibsoni and 1.4
      microg/mL against Plasmodium falciparum in vitro. The known compounds beta
      glucogallin (2), quercetin 3-O-beta-d-glucopyranosyl-(2-->1)-O-beta-d
      xylopyranoside (3), beta-sitosterol, and gallic acid were also isolated.
      Structures of these compounds were elucidated on the basis of their chemical and
      spectroscopic data.

PMID- 15844944
TI  - Intercedensides D-I, cytotoxic triterpene glycosides from the sea cucumber
      Mensamaria intercedens Lampert.
AB  - Six new triterpene glycosides, intercedensides D-I (1-6), were isolated from the
      whole bodies of the sea cucumber Mensamria intercedens Lampert, which is found in
      the South China Sea. Their structures were elucidated by extensive spectroscopic
      analysis (NMR and ESIMS) and chemical methods. lntercedensides D (1), E (2), G
      (4), and H (5) have a conjugated double bond system (22Z,24-diene) in the aglycon
      side chain, while intercedensides F (3) and I (6) have only a single double bond
      (24, 25) in this same chain. lntercedensides D-H (1-5) showed significant
      cytotoxicity (ED(50) 0.96-5.0 mug/mL) against 10 human tumor cell lines.

PMID- 15844945
TI  - Iso-, nor-, and dinor-spiculoic acids A, polyketides from the marine sponge
      Plakortis zyggompha.
AB  - The new iso-, nor-, and dinor-spiculoic acids A (1, 2, and 3, respectively) with
      a rare spiculane skeleton were isolated from the marine sponge Plakortis
      zyggompha, collected in the waters south of Martinique. The structural
      determination of the compounds was based on 1D and 2D NMR studies and mass
      spectral determinations. Compounds 1 and 2 showed weak cytotoxicity against the
      two tumor cell lines A549 and HT29.

PMID- 15844946
TI  - Chemical conversion of nocathiacin I to nocathiacin II and a lactone analogue of
      glycothiohexide alpha.
AB  - Nocathiacin I (1) was converted to its deoxy indole analogue, nocathiacin II (2),
      another natural product, by a unique and facile chemical process. This process
      was applied to nocathiacin IV (4), generating the lactone analogue of
      glycothiohexide alpha (5), which was also prepared from nocathiacin II by a mild
      hydrolytic process. In contrast to glycothiohexide alpha (3), this lactone
      analogue (5) was found to exhibit in vivo antibacterial efficacy in an animal
      (mouse) infection model.

PMID- 15844947
TI  - Manoyl oxide diterpenoids from Grindelia scorzonerifolia.
AB  - Two new norditerpenoids, 4beta-hydroxy-19-normanoyl oxide (1) and 4alpha-hydroxy
      18-normanoyl oxide (2), the new 18-O-alpha-l-arabinopyranosylmanoyl oxide (3a),
      and the known diterpenoids jhanol (4) and 18-hydroxy-13-epi-manoyl oxide (5) were
      isolated, together with other common plant constituents from an Argentine
      collection of Grindelia scorzonerifolia. The structures of the new compounds were
      established by extensive 1D and 2D NMR techniques and chemical transformations.
      Structural features of compounds 2 and 4 were verified by X-ray crystallographic
      analyses. The insecticidal effect of compound 3a was evaluated against the
      polyphagous pest Spodoptera frugiperda. Pupal and adult malformations leading to
      death occurred when 3a was incorporated in a larval diet at a concentration of
      100 ppm.

PMID- 15844948
TI  - Oxygenated lanostane-type triterpenoids from the fungus ganodermalucidum.
AB  - Two new triterpenoids, 20(21)-dehydrolucidenic acid A (1) and methyl 20(21)
      dehydrolucidenate A (2), and five new 20-hydroxylucidenic acids, 20
      hydroxylucidenic acid D(2) (3), 20-hydroxylucidenic acid F (4), 20
      hydroxylucidenic acid E(2) (5), 20-hydroxylucidenic acid N (6), and 20
      hydroxylucidenic acid P (7), were isolated from the fruiting body of the fungus
      Ganoderma ludicum, and their structures were established on the basis of
      spectroscopic methods.

PMID- 15844949
TI  - Holothurins B(2), B(3), and B(4), new triterpene glycosides from mediterranean
      sea cucumbers of the genus holothuria.
AB  - Triterpene glycosides of three species of the Mediterranean sea cucumbers
      Holothuria polii, Holothuria tubulosa, and Holothuria sp. were studied. Three new
      monosulfated biosides, holothurins B(2) (1), B(3) (2), and B(4) (3), along with
      the previously known holothurins A (4) and B (5) were isolated from the sea
      cucumber H. polii. Triterpene glycosides belonging to holothurin A and B groups
      were found in H. tubulosa, while only one individual glycoside, holothurin A (4),
      was isolated from Holothuria sp. Structures of new substances were elucidated on
      the basis of spectral data (2D NMR and MS). The significance of holothurins as
      chemotaxonomic markers of the animals belonging to the genus Holothuria and
      taxonomic status of some representatives of the holothurians studied are
      discussed.

PMID- 15844950
TI  - Biscopyran, a phytotoxic hexasubstituted pyranopyran produced by Biscogniauxia
      mediterranea, a fungus pathogen of cork oak.
AB  - A new phytotoxic hexasubstituted pyranopyran, biscopyran (3), was isolated
      together with phenylacetic acid (2) and previously isolated 5-methylmellein (1)
      from the liquid culture filtrates of Biscogniauxiamediterranea, a major fungal
      pathogen involved in oak decline in Sardinia. Biscopyran was characterized by
      spectroscopic methods as a new (Z)-2-methoxy-1-[7-((Z)-2-methoxybut-2-enoyl)
      3,4,5,6-tetramethyl-2H,7H-pyrano[2,3-b]pyran-2-yl]but-2-en-1-one. Biscopyran
      assayed at 0.26-0.026 mM concentration range caused epinasty on cork oak
      cuttings. On a nonhost plant, tomato, biscopyran caused wilting. Phenylacetic
      acid, assayed at the same concentration, was toxic to Q. suber, while on tomato
      cuttings it induced internal tissue collapse on the stem.

PMID- 15844951
TI  - Cremastrine, a pyrrolizidine alkaloid from Cremastra appendiculata.
AB  - A new pyrrolizidine alkaloid, cremastrine (1), was isolated from the bulbs of
      Cremastra appendiculata. Its configuration was determined by spectroscopic and
      chemical analyses. Compound 1 inhibited the binding of tritium-labeled N
      methylscopolamine to the muscarinic M3 receptor with a K(i) value of 126 nM.

PMID- 15844952
TI  - The psammaplysenes, specific inhibitors of FOXO1a nuclear export.
AB  - A small collection of marine natural product extracts was screened for compounds
      that would compensate lost tumor suppressor functionality in PTEN-deficient
      cells. From the most active extract, the previously unreported bromotyrosine
      derivative, psammaplysene A (1), was identified. Psammaplysene A compensates for
      PTEN loss by relocalizing the transcription factor FOXO1a to the nucleus.

PMID- 15844953
TI  - Constituents of the leaves and twigs of Calyptranthes pallens collected from an
      experimental plot in Southern Florida.
AB  - Fractionation of the chloroform-soluble extract of the leaves and twigs of
      Calyptranthes pallens, collected from an experimental plot in a hardwood forest
      of southern Florida, using a hormone-dependent human prostate carcinoma (LNCaP)
      tumor cell line, led to the isolation of a phloroglucinol derivative with a novel
      carbon skeleton, pallenic acid (1), and a new triterpenoid, 3beta-hydroxy
      18alpha,19alpha-urs-20-en-28-oic acid (2). The known compound methylene-bis
      aspidinol (3) was selectively active against the human oral epidermoid carcinoma
      (KB) cell line. Several known compounds of the ellagic acid, lignan,
      phloroglucinol, sterol, and triterpene types were also obtained in the present
      investigation.

PMID- 15844954
TI  - Calbistrin E and two other new metabolites from an Australian isolate of
      Penicillium striatisporum.
AB  - An Australian isolate of Penicillium striatisporum collected near Shalvey, New
      South Wales, exhibited selective antifungal activity against Candida albicans
      versus Saccharomyces cerevisiae. Bioassay-directed fractionation yielded members
      of the rare class of fungal metabolites known as the calbistrins. These included
      a new example of this structure class, calbistrin E (1), as well as the known
      polyenes calbistrin C (2) and deformylcalbistrin A (3). Also recovered from P.
      striatisporum were new triene and butenolide acids, striatisporin A (4) and
      striatisporolide A (5), together with the known fungal metabolites versiol (6)
      and (+)-hexylitaconic acid (7). Structures for all metabolites were determined by
      detailed spectroscopic analysis.

PMID- 15844955
TI  - Ochtodene derivatives from the red alga Carpopeltis crispata.
AB  - Red algae are well known as a source of halogenated monoterpenes such as
      derivatives of ochtodene. From Carpopeltis crispata, we have isolated four new
      ochtodene derivatives: dibromodichloro-, dibromochloro-, and
      bromodichlorocyclomonoterpenes. The structures of these monoterpenes were
      confirmed by NMR and mass spectroscopy and compared with spectral data in the
      literature.

PMID- 15844956
TI  - Diterpenoids from the aerial parts of Plectranthus ornatus.
AB  - Phytochemical investigation of a hexane extract of the aerial parts of
      Plectranthus ornatus yielded three new neoclerodane diterpenoids (1-3), two
      labdane diterpenes (4 and 5) obtained for the first time as natural products, and
      several previously known substances. The structures and relative stereochemistry
      of 1-5 were established mainly on the basis of NMR spectroscopic studies and by
      comparison with related compounds.

PMID- 15844957
TI  - Chemical constituents of the fruits of Morinda citrifolia (Noni) and their
      antioxidant activity.
AB  - Purification of a n-BuOH-soluble partition of the MeOH extract of Morinda
      citrifolia (Noni) fruits led to the isolation of two new iridoid glucosides,
      6alpha-hydroxyadoxoside (1) and 6beta,7beta-epoxy-8-epi-splendoside (2), as well
      as 17 known compounds, americanin A (3), narcissoside (4), asperuloside,
      asperulosidic acid, borreriagenin, citrifolinin B epimer a, citrifolinin B epimer
      b, cytidine, deacetylasperuloside, dehydromethoxygaertneroside, epi
      dihydrocornin, d-glucose, d-mannitol, methyl alpha-d-fructofuranoside, methyl
      beta-d-fructofuranoside, nicotifloroside, and beta-sitosterol 3-O-beta-d
      glucopyranoside. The structures of the new compounds were determined by
      spectroscopic data interpretation. Compound 4, borreriagenin, cytidine,
      deacetylasperuloside, dehydromethoxygaertneroside, epi-dihydrocornin, methyl
      alpha-d-fructofuranoside, and methyl beta-d-fructofuranoside were isolated for
      the first time from M. citrifolia. The antioxidant activity was evaluated for all
      isolates in terms of both DPPH and ONOO(-) bioassays. The neolignan, americanin A
      (3), was found to be a potent antioxidant in these assays.

PMID- 15844958
TI  - New targets in diarrhetic shellfish poisoning control.
AB  - The toxic profile of dinoflagellates varies even among identical species, raising
      an interesting question about the mechanism of toxin regulation and production.
      In consequence, it also poses a considerable problem in their control methods. In
      this paper, we report on the isolation and structural elucidation of several new
      ester derivatives of okadaic acid (OA) from artificial cultures of the genus
      Prorocentrum. These new compounds enlarge the range of target molecules that must
      be considered in the monitoring programs.

PMID- 15844959
TI  - Oxylipins arabidopsides C and D from Arabidopsis thaliana.
AB  - Two new oxylipins, arabidopsides C (1) and D (2), were isolated from the aerial
      parts of Arabidopsis thaliana, and the structures of 1 and 2 were elucidated
      using spectroscopic data, primarily NMR and MS, and chemical means. Arabidopsides
      C (1) and D (2) are rare digalactosyl diacylglycerides containing 12
      oxophytodienoic acid and/or dinor-oxophytodienoic acid. Arabidopside D (2) and
      arabidopsides A (3) and B (4), which were also isolated from this plant,
      exhibited inhibitory effects on the growth of the root of cress (Lepidium
      sativum) seedlings at 5 x 10(-5) mol/L.

PMID- 15844960
TI  - Majusculoic acid, a brominated cyclopropyl fatty acid from a marine
      cyanobacterial mat assemblage.
AB  - The novel antifungal compound majusculoic acid was isolated from a cyanobacterial
      mat microbial community. The structure of majusculoic acid was solved by
      interpretation of mass spectrometric and NMR data and conversion to the
      corresponding methyl ester. Majusculoic acid exhibits antifungal activity against
      Candida albicans ATCC 14503 (MIC 8 microM).

PMID- 15844961
TI  - Production of 8-demethylgeldanamycin and 4,5-epoxy-8-demethylgeldanamycin from a
      recombinant strain of Streptomyces hygroscopicus.
AB  - Two new geldanamycin derivatives produced by genetic engineering of Streptomyces
      hygroscopicus strain K309-27-1 were isolated and characterized. Removal of the 8
      methyl group of geldanamycin was achieved by replacing the AT4 domain of the
      polyketide synthase with a malonyl AT domain. The resulting strain produced 8
      demethyl geldanamycin (2) and 4,5-epoxy-8-demethylgeldanamycin (3). The
      structures of both molecules were elucidated through interpretation of 1D and 2D
      NMR data as well as comparison with authentic geldanamycin derivatives. Compounds
      2 and 3 displayed moderate cytotoxicity against the human breast cancer cell line
      SK-BR-3.

PMID- 15844962
TI  - Tenellones A and B from a Diaporthe sp.: two highly substituted benzophenone
      inhibitors of parasite cGMP-dependent protein kinase activity.
AB  - Parasite cGMP-dependent protein kinase (PKG) has been recently validated as a
      biochemical target for the treatment of coccidiosis. To discover new
      anticoccidial leads, we have screened our library of natural product extracts for
      inhibitors of parasite PKG. Bioassay-guided fractionation of the microbial
      extracts has led to the discovery of tenellones A (2) and B (3), two new highly
      substituted benzophenones. The isolation, structure, and activity of these
      compounds are described.

PMID- 15844963
TI  - Leptolide, a new furanocembranolide diterpene from Leptogorgia alba.
AB  - Six furanocembranolides (1-6) and one pseudopterolide (7) have been isolated from
      the octocorals Leptogorgia alba and Leptogorgia rigida, collected on the Pacific
      coast of Panama. Compound 1, named leptolide, has a new structure closely related
      to the neurotoxin lophotoxin (3). The X-ray structures of 1-3 were determined,
      and the absolute configurations of 2-7 are discussed. Compounds 1-7 were
      evaluated in vitro against drug-resistant Plasmodium falciparum.

PMID- 15844964
TI  - Guttiferone I, a new prenylated benzophenone from Garcinia humilis as a liver X
      receptor ligand.
AB  - Liver X receptors (LXR) have been implicated in cholesterol homeostasis. Agonists
      of LXR are expected to increase cholesterol efflux, lower LDL, and raise HDL
      levels. Screening of a natural product library of plant extracts using a LXR-SPA
      binding assay and bioassay-guided fractionation of the bark and stem extract of
      Garcinia humilis led to the discovery of a new polyisoprenylated benzophenone
      named guttiferone I (1). The IC(50) value for this compound in the LXRalpha-SPA
      binding assay was 3.4 muM. Details of the isolation, structure elucidation, and
      ligand binding activity of 1 are described.

PMID- 15844965
TI  - Structures and aldose reductase inhibitory effects of bromophenols from the red
      alga Symphyocladia latiuscula.
AB  - Three new bromophenols, 2,2',3,6,6'-pentabromo-3',4,4',5-tetrahydroxydibenzyl
      ether (1), bis(2,3,6-tribromo-4,5-dihydroxyphenyl)methane (2), and 2,2',3,5',6
      pentabromo-3',4,4',5-tetrahydroxydiphenylmethane (3), were isolated from the red
      alga Symphyocladia latiuscula. Two bromophenols, 2,3,6-tribromo-4,5
      dihydroxymethylbenzene (4) and 2,3,6-tribromo-4,5-dihydroxybenzaldehyde (5), were
      also reported for the first time as natural products. Their structures were
      elucidated on the basis of chemical and spectroscopic methods including HREIMS,
      HRFABMS, and 1D and 2D NMR spectral techniques. Compounds 1-5 exhibited
      significant aldose reductase inhibitory activity.

PMID- 15844966
TI  - Cyclic peptides of the nocardamine class from a marine-derived bacterium of the
      genus Streptomyces.
AB  - Two new cyclic peptides (2 and 3) along with the previously reported nocardamine
      (1) were isolated from the culture broth of an actinomycete of the genus
      Streptomyces isolated from an unidentified marine sponge. On the basis of the
      results of combined spectral analyses, the structures of the new compounds were
      defined to be the dehydroxy and desmethylenyl derivatives of nocardamine,
      respectively. The new compounds exhibited weak inhibition against the enzyme
      sortase B.

PMID- 15844967
TI  - Microbial hydroxylation of bufalin by Cunninghamella blakesleana and Mucor
      spinosus.
AB  - The microbial transformation of a cytotoxic bufadienolide, bufalin (1), was
      carried out using two strains of filamentous fungi. Cunninghamella blakesleana
      catalyzed the specific 12alpha-hydroxylation of bufalin and produced 12alpha
      hydroxybufalin (2) and 7beta,12alpha-dihydroxybufalin (3) as the major
      metabolites, together with 7beta-hydroxybufalin (4) and 12beta-hydroxybufalin (5)
      in low yields. Two minor products were isolated from the culture broth of Mucor
      spinosus and were identified as 7beta,15alpha-dihydroxybufalin (6) and
      5beta,7beta-dihydroxybufalin (7), respectively. Metabolites 2, 3, 6, and 7 are
      new compounds, and their structures were fully characterized by NMR and MS
      spectroscopy.

PMID- 15844968
TI  - Development and comparison of the substrate scope of Pd-catalysts for the aerobic
      oxidation of alcohols.
AB  - [reaction: see text] Three catalysts for aerobic oxidation of alcohols are
      discussed and the effectiveness of each is evaluated for allylic, benzylic,
      aliphatic, and functionalized alcohols. Additionally, chiral nonracemic
      substrates as well as chemoselective and diastereoselective oxidations are
      investigated. In this study, the most convenient system for the Pd-catalyzed
      aerobic oxidation of alcohols is Pd(OAc)(2) in combination with triethylamine.
      This system functions effectively for the majority of alcohols tested and uses
      mild conditions (3 to 5 mol % of catalyst, room temperature).
      Pd(IiPr)(OAc)(2)(H(2)O) (1) also successfully oxidizes the majority of alcohols
      evaluated. This system has the advantage of significantly lowering catalyst
      loadings but requires higher temperatures (0.1 to 1 mol % of catalyst, 60 degrees
      C). A new catalyst is also disclosed, Pd(IiPr)(OPiv)(2) (2). This catalyst
      operates under very mild conditions (1 mol %, room temperature, and air as the
      O(2) source) but with a more limited substrate scope.

PMID- 15844969
TI  - Synthesis of 2,2-disubstituted pyrrolidine-4-carboxylic acid derivatives and
      their incorporation into beta-peptide oligomers.
AB  - [reaction: see text] We have recently shown that members of a new class of beta
      peptides, containing 2,2-disubstituted pyrrolidine-4-carboxylic acid residues,
      display discrete conformational preferences despite the impossibility of internal
      hydrogen bonding (Huck et al. J. Am. Chem. Soc. 2003, 125, 9035). Here we
      describe the synthesis of a variety of 2,2-disubstituted pyrrolidine-4-carboxylic
      derivatives that bear a diverse set of side chains and protecting groups suitable
      for oligomer synthesis. In addition, we discuss coupling methods for construction
      of oligomers in solution and on solid phase. Non-hydrogen bonded foldamers such
      as those generated from 2,2-disubstituted pyrrolidine-4-carboxylic acids may be
      useful in biomedical applications because the low intrinsic polarity of their
      backbones may promote bioavailability.

PMID- 15844970
TI  - Palladium-diphosphite catalysts for the asymmetric allylic substitution
      reactions.
AB  - [structure: see text] We have designed a series of diphosphite ligands to study
      the effect of the backbone, the size of the chelate ring, and the substituents of
      the biphenyl moieties and to determine the scope of this type of ligand in the Pd
      catalyzed asymmetric substitution reactions of different types of substrates.
      Good-to-excellent activities and enantioselectivities have been obtained for
      disubstituted linear substrate 11 (TOF's up to >2000 mol x (mol x h)(-1), ee
      values up to 99%) and cyclic substrate 14 (TOF up to 285 mol x (mol x h)(-1), ee
      values up to 92%). However, these ligands are inadequate for the Pd-catalyzed
      allylic alkylation of monosubstituted linear substrates because they provide low
      enantioselectivities.

PMID- 15844971
TI  - Diastereoselective ring expansion of beta-lactams toward gamma-lactams via N
      acyliminium intermediates.
AB  - [reaction: see text] The diastereoselective synthesis of highly functionalized
      gamma-lactams starting from 4-(1-bromoalkyl)-2-azetidinones via N-acyliminium
      intermediates is described. The carbenium ions, formed by dissociation of bromide
      from 4-(1-bromoalkyl)-2-azetidinones in polar medium, are converted via a ring
      expansion toward N-acyliminium ions, which are susceptible to attack of oxygen,
      nitrogen, and carbon nucleophiles. In this way, a variety of 5-hydroxy-, 5
      alkoxy, 5-cyano-, 5-allylamino- and 5-azido-4,4-dimethyl-2-pyrrolidinones were
      synthesized. It was found that dehydrobromination of 4-(1-bromoalkyl)-2
      azetidinones constituted an important side reaction when the title reactions were
      carried out in DMSO. When THF was used as a solvent, generally no
      dehydrobromination was observed, implying that higher yields of gamma-lactams
      were obtained in THF compared to reactions performed in DMSO. Also substituents
      of the 4-(1-bromoalkyl)-2-azetidinones play an important role concerning the
      obtained diastereoselectivity and the degree of dehydrobromination.

PMID- 15844972
TI  - Reaction of metalated nitriles with enones.
AB  - [reaction: see text] There have been a number of reports of the kinetic conjugate
      (1,4) addition of metalated arylacetonitriles to enones. Several proposals have
      been made to explain this behavior based on nucleophile structure or aggregation
      state or on the HSAB properties of the reactants. A reexamination of these
      studies showed that in each case the 1,4 adducts resulted from equilibration of
      the kinetically formed 1,2 adducts to the more stable 1,4 adducts. Thus, no
      conclusions about the origins of 1,4 selectivity can be drawn from these
      experiments. The 1,2 addition, retro-1,2 addition, 1,4 addition, and retro-1,4
      addition of lithiophenylacetonitrile to benzylideneacetone were examined, and a
      free energy level diagram was constructed for the reaction.

PMID- 15844973
TI  - Synthesis of selected LeY and KH-1 analogues: a medicinal chemistry approach to
      vaccine optimization.
AB  - [structure: see text] As part of our ongoing anticancer vaccine program, we
      recently found that antibodies generated in response to the KH-1-KLH construct
      recognized not only KH-1 antigen but also the Lewis Y (Le(y)) antigen as well,
      with antibody titer levels much higher than those observed after immunization
      with individual Le(y)-KLH vaccine constructs. In an attempt to explore the
      structure-antigenic relationship of these carbohydrate epitopes, several
      analogues of both KH-1 and Le(y) were synthesized. A convergent synthetic
      approach to the analogues was designed on the basis of well-established glycal
      methodology, employing a minimum number of building blocks to generate competent
      antigens with high stereoselectivity and reasonable yield.

PMID- 15844974
TI  - Preparative fluorous mixture synthesis of diazonium-functionalized
      oligo(phenylene vinylene)s.
AB  - [structure: see text] A series of building blocks for the synthesis of
      oligo(phenylene vinylene)s (OPVs) and hybrid oligomers were prepared, and
      alternating Heck coupling and Horner-Wadswoth-Emmons (HWE) reactions were used to
      couple the building blocks. Model studies were carried out to optimize the
      reaction strategies. The products were made to bear aryl diazonium
      functionalities that allow them to be used as surface grafting moieties in hybrid
      silicon/molecule assemblies. A library of OPV and hybrid oligomer tetramers was
      synthesized using fluorous mixture synthesis (FMS). The fluorous tags, which are
      secondary amines bearing different numbers of fluorine atoms, were synthesized
      and used as phase tags in mixture synthesis. The tags and substrates were
      anchored together by triazene linkages. The mixture synthesis was monitored by
      analytical HPLC on a fluorous column, and isolation of final OPV and hybrid
      oligomer tetramers was achieved by preparative HPLC. At the end of the FMS, after
      demixing, the tagged products were detagged by cleaving the triazene linkage and
      generating a series of aryl diazonium compounds. The fluorous tags could be
      recovered and reused. The NMR spectra of the 1-aryl-3,3-dialkyltriazenes are
      discussed.

PMID- 15844975
TI  - Reaction of 2-methoxy-3H-azepine with NBS: efficient synthesis of 2-substituted
      2H-azepines.
AB  - [reaction: see text] The reaction of 2-methoxy-3H-azepines, in the presence or
      absence of a nucleophile, with N-bromosuccinimide (NBS) gave a regioselective 1,4
      adduct from which the corresponding 2H-azepine derivatives were formed via base
      promoted hydrogen bromide elimination, generally in moderate to quantitative
      yield. Competitive formation of 4-bromo-2-methoxy-3H-azepine by electrophilic
      substitutuion or 3H-azepin-2-yl 2H-azepin-2-yl ether by transetherification was
      minimized at lower reaction temperatures. Quantitative substitution of 2
      (2',4',6'-trichlorophenoxy)-2H-azepine derivatives, formed in moderate yield from
      the respective 3H-azepine and NBS in the presence of 2,4,6-trichlorophenol (TCP),
      by various nucleophiles gave the corresponding 2-substituted 2H-azepine. Among
      these nucleophiles were alkanethiol and alkylamine that are not tolerated in the
      reaction of 3H-azepine and NBS.

PMID- 15844976
TI  - Experimental and theoretical study of stabilization of delocalized forms of
      semibullvalenes and barbaralanes by dipolar and polarizable solvents. Observation
      of a delocalized structure that is lower in free energy than the localized form.
AB  - [reaction: see text] UV/vis spectra of thermochromic semibullvalenes 1 and
      barbaralanes 2, which undergo rapid degenerate Cope rearrangements, display
      temperature-dependent shoulders (1b, 1d, 1e) or absorption maxima (1c, 2c, 2f) at
      the low-energy side of their strong UV bands. These long-wavelength absorptions
      are ascribed to Franck-Condon transitions from delocalized structures 1(deloc)
      and 2(deloc). Gibbs free energy differences, DeltaG*, between delocalized and
      localized forms were calculated from the temperature dependence of the long
      wavelength absorptions. Dipolar and polarizable solvents strongly affect and even
      may reverse the relative stabilities of the localized and delocalized forms of
      1c, 2c, and 2f. For example, DeltaG*(2c) = 8 kJ mol(-)(1) in cyclohexane, 2 kJ
      mol(-)(1) in dimethylformamide, and -3 kJ mol(-)(1) in N,N'-dimethylpropylene
      urea (DMPU), so that (2c(deloc))(DMPU) becomes the global minimum. In contrast to
      the case for 2c, the intensities of the long-wavelength shoulders of the yellow
      semibullvalenes 1b, 1d, and 1e are only moderately influenced by solvents, and
      the rates of Cope rearrangements of the nonthermochromic, colorless barbaralanes
      2a and 2b, determined by NMR methods, are almost solvent-invariant. In search of
      the solute properties that are decisive in determining the influence of solvent
      upon DeltaG*, electrical dipole and quadrupole moments and molecular
      polarizabilities have been calculated using the B3LYP/6-31G* method and solvation
      energies have been computed with the conductorlike polarized continuum model
      (CPCM). The results of these calculations indicate that the solvent effects are
      due to the greater polarity and polarizability of the delocalized structures
      relative to the localized structures.

PMID- 15844977
TI  - Conformational mobility of thianthrene-5-oxide.
AB  - [reaction: see text] Data on the apparent dipole moment of thianthrene-5-oxide
      (1) and (1)H NMR spectra in different solvents support the conformational
      mobility of 1, which flaps between two limit boat conformations with the sulfinyl
      group in pseudoequatorial and pseudoaxial positions, respectively. The
      conformational equilibrium of 1 occurs too fast for the (1)H NMR (500 MHz) time
      scale even at -130 degrees C, and the equilibrium constant has not been
      determined. The apparent dipole moments of 1 in n-hexane and 1,4-dioxane and the
      (1)H NMR spectra of 1 and the model compounds cis- and trans-thianthrene-5,10
      dioxides (2) and thianthrene (5) in different solvents and at various
      temperatures confirm that the relative position of the conformational equilibrium
      of 1 is solvent-dependent, and more polar solvents favor the conformation with
      the sulfoxide group in the pseudoaxial position (1(')(ax)). Variable-temperature
      (1)H NMR spectra have established the interconversion barrier of trans-2 and
      confirmed that the conformational equilibrium of cis-2 is strongly displaced
      toward the conformation with both sulfinyl groups in the pseudoequatorial
      position. The (1)H NMR data support the transannular interaction of the
      functional groups in 1 and trans-2.

PMID- 15844978
TI  - Photochemistry of substituted dibenzothiophene oxides: the effect of trapping
      groups.
AB  - [reaction: see text] Photolyses of dibenzothiophene sulfoxides (DBTOs) with
      intramolecular trapping functionalities attached in the 4-position show higher
      quantum yields of deoxygenation. Deoxygenation quantum yields are also less
      solvent dependent for the substituted DBTOs. Product analysis shows a detectable
      amount of intramolecular O-trapped products and suggests that solvent effects
      observed in previous studies of DBTO derive at least mainly from the reactivity
      between the oxidizing species that is released, presumably O((3)P), and the
      solvent, rather than from other macroscopic solvent parameters.

PMID- 15844979
TI  - Indium-mediated asymmetric Barbier-type allylation of aldimines in alcoholic
      solvents: synthesis of optically active homoallylic amines.
AB  - [reaction: see text] Chiral aldimines derived from phenylglycinol were
      diastereoselectively allylated with indium powder/allyl bromide in alcoholic
      solvents. Both aliphatic and aromatic aldimines provided good yield of the
      desired products with high diastereoselectivity. A racemization-free protocol for
      removal of the phenylglycinol auxiliary was also developed. The stereochemical
      assignment of the homoallylic amine was made by NMR spectroscopy and a transition
      state model was proposed to explain the selectivity.

PMID- 15844980
TI  - Antioxidant properties of natural and synthetic chromanol derivatives: study by
      fast kinetics and electron spin resonance spectroscopy.
AB  - [structure: see text] Chromanol-type compounds act as antioxidants in biological
      systems by reduction of oxygen-centered radicals. Their efficiency is determined
      by the reaction rate constants for the primary antioxidative reaction as well as
      for disproportionation and recycling reactions of the antioxidant-derived
      radicals. We studied the reaction kinetics of three novel chromanols: cis- and
      trans-oxachromanol and the dimeric twin-chromanol, as well as ubichromanol and
      ubichromenol, in comparison to alpha-tocopherol and pentamethylchromanol. The
      antioxidant-derived radicals were identified by optical and electron spin
      resonance spectroscopy (ESR). The kinetics of the primary antioxidative reaction
      and the disproportionation of the chromanoxyl radicals were assessed by stopped
      flow photometry in different organic solvents to simulate the different
      polarities associated with biomembranes. Furthermore, the reduction of the
      chromanoxyl radicals by ubiquinol and ascorbate was measured after laser-induced
      one-electron chromanol oxidation in ethanol and in a micellar system,
      respectively. The rate constants showed that twin-chromanol had better radical
      scavenging properties than alpha-tocopherol and a significantly slower
      disproportionation rate of its corresponding chromanoxyl radical. In addition,
      the radical derived from twin-chromanol is reduced by ubiquinol and ascorbate at
      a faster rate than the tocopheroxyl radical. Finally, twin-chromanol can deliver
      twice as many reducing equivalents, which makes this compound a promising new
      candidate as artificial antioxidant in biological systems.

PMID- 15844981
TI  - Chemoenzymatic taxanes approach using both enantiomers of the same building
      block. 2. Taxol CD ring unit.
AB  - [reaction: see text] The enantioselective synthesis of the Taxol CD ring unit has
      been achieved starting from an enantiopure building block, the enantiomer of
      those previously utilized in the synthesis of the A ring unit. The key features
      of the present synthesis are astute use of both enantiomers of the same building
      block and complete control in the construction of five consecutive chiral
      centers.

PMID- 15844982
TI  - Reactions of indole derivatives with oxiranes and aziridines on silica. Synthesis
      of beta-carbolin-1-one mimic of pancratistatin.
AB  - [reaction: see text] Indole and several indoles functionalized at C-2 were
      condensed with oxiranes, vinyloxiranes, aziridines, and vinylaziridines in the
      solid state on the surface of silica. The yields of these reactions were compared
      to those obtained from Lewis acid-catalyzed ring-opening reactions performed in
      solution and found to be superior in each case. The solid-phase aziridine opening
      constituted a key step in the synthesis of the beta-carbolin-1-one mimic of
      pancratistatin. Methyl 2-indolecarboxylate was found to react on the silica gel
      surface with N-tosylvinylaziridine in 68% yield. A nine-step synthesis of the
      pancratistatin mimic has been attained. The additional key transformation in this
      synthesis involved silica gel-catalyzed opening of an epoxide and hydrolysis of
      an acetonide. Detailed experimental procedures and full characterization are
      reported for all new compounds.

PMID- 15844983
TI  - Direct synthesis of palladium porphyrins from acyldipyrromethanes.
AB  - [reaction: see text] Palladium porphyrins are valuable photosensitizers and
      luminescent agents in biology and materials chemistry. New methodology is
      described wherein a 1-acyldipyrromethane is converted into the palladium chelate
      of a trans-A(2)B(2) porphyrin via a one-flask reaction. The reaction entails self
      condensation of the 1-acyldipyrromethane in refluxing ethanol containing KOH (5
      10 mol equiv) and Pd(CH(3)CN)(2)Cl(2) (0.6 mol equiv) exposed to air. This direct
      route to palladium porphyrins is more expedient than the four steps of the
      traditional synthesis: (1) reduction of the 1-acyldipyrromethane; (2) acid
      catalyzed condensation; (3) oxidation of the porphyrinogen intermediate; and (4)
      metal insertion. The new synthesis requires neither acid nor DDQ and formally
      entails only a 2e(-) + 2H(+) oxidation overall versus the traditional multistep
      synthesis which requires a 2e(-) + 2H(+) reduction per each 1-acyldipyrromethane
      (4e(-) + 4H(+) overall) followed by a 6e(-) + 6H(+) oxidation. The analogous
      reaction of a 1,9-diacyldipyrromethane and a dipyrromethane also gives the
      palladium porphyrin. Seven palladium porphyrins have been prepared in yields of
      25-57%. The direct route also can be used with Cu(OAc)(2).H(2)O to give the
      copper porphyrin albeit in low yield. In summary, this methodology readily
      affords palladium porphyrins directly from acyldipyrromethanes.

PMID- 15844984
TI  - Synthesis of polycyclic aromatics and heteroaromatics via electrophilic
      cyclization.
AB  - [reaction: see text] A variety of substituted polycyclic aromatics are readily
      prepared in good to excellent yields under very mild reaction conditions by the
      reaction of 2-(1-alkynyl)biphenyls with ICl, I(2), NBS, and p-O(2)NC(6)H(4)SCl.
      This methodology readily accommodates various functional groups and has been
      successfully extended to systems containing a variety of polycyclic and
      heterocyclic rings.

PMID- 15844985
TI  - New glycosidase activated nitric oxide donors: glycose and 3
      morphorlinosydnonimine conjugates.
AB  - [reaction: see text] To achieve site specific delivery of nitric oxide (NO), a
      new class of glycosidase activated NO donors has been developed. Glucose,
      galactose, and N-acetylneuraminic acid were covalently coupled to 3
      morphorlinosydnonimine (SIN-1), a mesoionic heterocyclic NO donor, via a
      carbamate linkage at the anomeric position. The beta-glycosides were successfully
      prepared for these conjugates, while the alpha-glycosidic compounds were very
      unstable. The new stable sugar-NO conjugates could release NO in the presence of
      glycosidases. Such NO prodrugs may be used as enzyme activated NO donors in
      biomedical research.

PMID- 15844986
TI  - 1,4-Difluoro-2,5-dimethoxybenzene as a precursor for iterative double benzyne
      furan Diels-Alder reactions.
AB  - [reaction: see text] The use of 1,4-difluoro-2,5-dimethoxybenzene as a novel
      precursor for iterative two-directional benzyne-furan Diels-Alder reactions,
      using a range of 2- and 3-substituted furans, is reported. Substituted
      oxabenzonorbornadienes were synthesized following the initial Diels-Alder
      reaction, which upon ring opening under acidic conditions gave substituted
      naphthol derivatives. Highly substituted anthracenols were generated in the
      second benzyne-furan Diels-Alder reaction following acid-catalyzed isomerization
      of the cycloadducts.

PMID- 15844987
TI  - Kinetics and mechanism of the pyridinolysis of S-2,4-dinitrophenyl 4-substituted
      thiobenzoates.
AB  - [reaction: see text] The reactions of S-2,4-dinitrophenyl 4-methyl (1), S-2,4
      dinitrophenyl 4-H (2), S-2,4-dinitrophenyl 4-chloro (3), and S-2,4-dinitrophenyl
      4-nitro (4) thiobenzoates with a structurally homogeneous series of pyridines are
      subjected to a kinetic investigation in 44 wt % ethanol-water, at 25.0 degrees C
      and an ionic strength of 0.2 M (KCl). The reactions are studied
      spectrophotometrically (420 nm) by monitoring the appearance of 2,4
      dinitrobenzenethiolate anion. Pseudo-first-order rate coefficients (k(obsd)) are
      obtained for all the reactions, employing excess of amine. The plots of k(obsd)
      vs [free pyridine] at constant pH are linear with the slopes (k(N)) independent
      of pH. The Bronsted-type plots (log k(N) vs pK(a) of the conjugate acid of the
      pyridines) are curved for all the reactions. The Bronsted curves are in
      accordance with stepwise mechanisms, through a zwitterionic tetrahedral
      intermediate (T(+/-)), and a change in the rate-limiting step. An equation based
      on this hypothesis accounts well for the experimental points. The Bronsted lines
      were calculated with the following parameters: Reactions of thiolbenzoate 1:
      beta(1) 0.33 (slope at high pK(a)), beta(2) 0.95 (slope at low pK(a)), and
      pK(a)(0) = 8.5 (pK(a) at the curvature center); thiolbenzoate 2: beta(1) 0.30,
      beta(2) 0.88, and pK(a)(0) = 8.9; thiolbenzoate 3: beta(1) 0.33, beta(2) 0.89,
      and pK(a)(0) = 9.5; thiolbenzoate 4: beta(1) 0.21, beta(2) 0.97, and pK(a)(0) =
      9.9. The increase of the pK(a)(0) value with the increase of the electron
      withdrawing effect of the acyl substituent is explained by the argument that the
      rate of pyridine expulsion from T(+/-) (k(-)(1)) is favored over that of 2,4
      dinitrobenzenethiolate leaving (k(2)), i.e., k(-)(1)/k(2) increases, as the acyl
      group becomes more electron withdrawing. The pK(a)(0) values for the title
      reactions are smaller than those for the reactions of the corresponding 4
      nitrophenyl 4-substituted thiolbenzoates with the same pyridine series. This is
      explained by the larger k(2) value for 2,4-dinitrobenzenethiolate leaving from
      T(+/-) compared with 4-nitrobenzenethiolate, which results in lower k(-)(1)/k(2)
      ratios for the dinitro derivatives. The pK(a)(0) value obtained for the
      pyridinolysis of thiolbenzoate 2 (pK(a)(0) = 8.9) is smaller than that found for
      the same aminolysis of 2,4-dinitrophenyl benzoate (pK(a)(0) = 9.5). This is
      attributed to the greater nucleofugality from T(+/-) of 2,4
      dinitrobenzenethiolate (pK(a) of conjugate acid 3.4) relative to 2,4
      dinitrophenoxide (pK(a) of conjugate acid 4.1). The title reactions are also
      compared with the aminolysis of similar esters to assess the effect of the amine
      nature and leaving and acyl groups on the kinetics and mechanism.

PMID- 15844988
TI  - Synthesis, structure, and reactivity of novel 3,4-diphosphacyclobutenes bearing
      silyl groups.
AB  - [reaction: see text] Copper-mediated homocoupling of sterically hindered 2-(2,4,6
      tri-tert-butylphenyl)-1-trialkylsilyl-2-phosphaethenyllithiums afforded 1,2
      bis(trialkylsilyl)-3,4-diphosphacyclobutenes (1,2-dihydrodiphosphetenes) through
      a formal electrocyclic [2+2] cyclization in the P=C-C=P skeleton as well as 2
      trimethylsilyl-1,4-diphosphabuta-1,3-diene. Reduction of 1,2-bis(trimethylsilyl)
      3,4-diphosphacyclobutenes followed by quenching with electrophiles afforded ring
      opened products, (E)-1,2-bis(phosphino)-1,2-bis(trimethylsilyl)ethene and (Z)-2,3
      bis(trimethylsilyl)-1,4-diphosphabut-1-ene. The structures of the ring-opened
      products indicated E/Z isomerization around the C=C bond after P-P bond cleavage
      of 5, and the isomerization of the P-C=C skeleton. Ring opening of 1,2
      bis(trimethylsilyl)-3,4-diphosphacyclobutenes affording (E,E)- and (Z,Z)-1,4
      diphosphabuta-1,3-dienes was observed upon desilylation.

PMID- 15844989
TI  - Multicomponent synthesis of 2-imidazolines.
AB  - [reaction: see text] A multicomponent reaction (MCR) between amines, aldehydes,
      and isocyanides bearing an acidic alpha-proton gives easy access to a diverse
      range of highly substituted 2-imidazolines. The limitations of the methodology
      seem to be determined by the reactivity of the isocyanide and by the steric bulk
      on the in situ generated imine rather than by the presence of additional
      functional groups on the imine. Less reactive isocyanides, for example p
      nitrobenzyl isocyanide 25a, react successfully with amines and aldehydes, using a
      catalytic amount of silver(I) acetate. Some of the resulting p-nitrophenyl
      substituted 2-imidazolines undergo air oxidation to the corresponding imidazoles.
      Differences in reactivity of the employed isocyanides are explained with use of
      DFT calculations. Difficult reactions with ketones instead of aldehydes as the
      oxo-compound in this MCR are promoted by silver(I) acetate as well.

PMID- 15844990
TI  - Novel vinyl phosphonates and vinyl boronates by halogenation, allylation, and
      propargylation of alpha-boryl- and alpha-phosphonozirconacyclopentenes.
AB  - [structure: see text] Alpha-phosphonozirconacyclopentenes or alpha
      borylzirconacyclopentenes react by bromination, iodination, allylation, and
      propargylation to generate unique vinyl boronates and vinyl phosphonates not
      obtainable by other methods. The reaction proceeds in two steps, with both high
      regio- and stereoselectivity. With the vinyl boronates, the Zr-Csp2 bond is
      initially cleaved by 1 equiv of electrophile. With the phosphonates, either the
      Zr-Csp2 bond (allyl bromide, Br(2)) or the Zr-Csp3 bond (I(2), propargyl bromide)
      may be initially cleaved. The addition of a second equivalent of an electrophile
      results in disubstitution.

PMID- 15844991
TI  - The phane properties of anti-[2.2](1,4)biphenylenophane.
AB  - [structure: see text] Anti-[2.2](1,4)biphenylenophane (4) was synthesized from de
      Meijere's tetrabromo[2.2]paracyclophane (5) through a four-step reaction
      sequence. Although an average separation of 3.09 A between the inner ring of the
      biphenylene units is normal for [2.2]paracyclophanes, a bond distance of 1.54
      Afor the ethano C-C bridge at room temperature is shorter than usual. In
      addition, trimethylsilyl-substituted anti-[2.2](1,4)biphenylenophane 8 sublimes
      at 220 degrees C under a pressure lower than 1 x10(-5) Torr without decomposition
      or thermal isomerization. The high thermal stability of 8 suggested that the
      ethano bridges of the biphenylenophanes are less strained than those of
      [2.2]paracyclophane. Bathochromic shifts are observed in their UV-vis absorption
      spectra. The phane state interactions of 4 and 8 were evidenced by the weak
      structureless fluorescent emission maximized at 537 and 550 nm in CH(2)Cl(2)
      along with longer relaxation lifetimes of 229 and 292 ps, respectively.

PMID- 15844992
TI  - Efficient access to 2-aryl-3-substituted benzo[b]thiophenes.
AB  - [reaction: see text] Benzo[b]thiophene derivatives are important in part because
      of their use as selective estrogen receptor modulators. They are usually
      synthesized by intramolecular cyclization. Here, we propose a method for the
      synthesis of 2-arylbenzo[b]thiophenes with heteroatoms at the 3-positions
      directly from the benzo[b]thiophene core by using an aromatic nucleophilic
      substitution reaction and Heck-type coupling. This methodology provides 2-aryl-3
      amino or phenoxybenzo[b]thiophenes in about 35% overall yield in 5 steps.

PMID- 15844993
TI  - Improving glycopeptide synthesis: a convenient protocol for the preparation of
      beta-glycosylamines and the synthesis of glycopeptides.
AB  - [reaction: see text] Herein we apply a recently introduced protocol using
      ammonium carbamate in methanol to the amination of crude chitobiose leading to
      1,beta-aminochitobiose. This simple, one-step procedure allows a facile
      preparation of unstable glycosylamines in contrast to the commonly implemented
      ammonium bicarbonate based amination of water-soluble carbohydrates. The new
      amination protocol leads to an improved synthesis of the key chitobiosyl
      asparagine building block for the SPPS of glycopeptides. The utility of the
      method is demonstrated with the synthesis of a 39-amino acid glycoprotein.

PMID- 15844994
TI  - Electrophilic cleavage of cyclopropylmethystannanes: an experimental comparison
      of sigma-sigma and sigma-pi conjugation.
AB  - [reaction: see text] Cyclopropylmethyltrimethylstannanes undergo electrophilic
      cyclopropane cleavage in chloroform with simple inorganic electrophiles (H(+),
      SO(2), I(2)) in a homologous reaction to the S(E)' cleavage of allylic stannanes.
      The sigma-sigma conjugation between the carbon-tin bond and cyclopropane orbitals
      observed spectroscopically in the parent cyclopropylmethyltrimethylstannane is
      responsible for a rate enhancement of ca. 10(2) toward iodinolysis, relative to
      comparable alkyl stannanes. This acceleration is considerably less, however, than
      the ca. 10(9)-fold rate enhancement provided by the corresponding sigma-pi
      conjugation in allylic stannanes. Methanol-tin coordination appears to reduce the
      activating influence of the metal, promoting methyl cleavage over cyclopropane
      fission with acid and iodine. Decreased sigma-sigma conjugation can also explain
      the decreased reactivity of cyclopropyltriphenylstannane compared with its
      trimethyltin counterpart. Cyclopropylmethylstannanes do not undergo the
      synthetically useful addition of aldehydes under conditions that facilitate the
      corresponding reaction of allylic stannanes.

PMID- 15844995
TI  - Transfer hydrogenation of activated C=C bonds catalyzed by ruthenium amido
      complexes: reaction scope, limitation, and enantioselectivity.
AB  - [reaction: see text] It was found that the chemoselectivity could be completely
      switched from C=O to C=C bonds in the transfer hydrogenation of activated
      alpha,beta-unsaturated ketones catalyzed by diamine-ruthenium complex. Moreover,
      this addition via metal hydride had been applied to the reduction of various
      activated olefins. The electron-withdrawing ability of functional groups
      substituted on C=C bonds at the alpha- or beta-position had strong influence on
      the reactivity. In addition, a wide variety of chiral diamine-Ru(II)-(arene)
      systems was investigated to explore the asymmetric transfer hydrogenation of
      prochiral alpha,alpha-dicyanoolefins. Two parameters had been systematically
      studied, (i) the structure of the N-sulfonylated chiral diamine ligands, in which
      several chiral diamines substituted on the benzene ring of DPEN were first
      reported, and (ii) the structure of the metal precursors, and high
      enantioselectivitiy (up to 89% ee) at the beta-carbon was obtained.

PMID- 15844996
TI  - Enantioselective nitrile anion cyclization to substituted pyrrolidines. A highly
      efficient synthesis of (3S,4R)-N-tert-butyl-4-arylpyrrolidine-3-carboxylic acid.
AB  - [reaction: see text] A practical asymmetric synthesis of N-tert-butyl
      disubstituted pyrrolidines via a nitrile anion cyclization strategy is described.
      The five-step chromatography-free synthesis of (3S,4R)-1-tert-butyl-4-(2,4
      difluorophenyl)pyrrolidine-3-carboxylic acid (2) from 2-chloro-1-(2,4
      difluorophenyl)-ethanone achieved a 71% overall yield. The cyclization substrate
      was prepared via a catalytic CBS asymmetric reduction, t-butylamine displacement
      of the chlorohydrin, and a conjugate addition of the hindered secondary amine to
      acrylonitrile. The key nitrile anion 5-exo-tet cyclization concomitantly formed
      the pyrrolidine ring with clean inversion of the C-4 center to afford 1,3,4
      trisubstituted chiral pyrrolidine in >95% yield and 94-99% ee. Diethyl
      chlorophosphate and lithium hexamethyldisilazide were shown to be the respective
      optimum activating group and base in this cyclization. The trans-cis mixture of
      the pyrrolidine nitrile undergoes a kinetically controlled epimerization/
      saponification to afford the pure trans-pyrrolidine carboxylic acid target
      compound in >99.9% chemical and optical purity. This chemistry was also shown to
      be applicable to both electronically neutral and rich substituted phenyl
      substrates.

PMID- 15844997
TI  - Computational evaluation of the evidence for tri-trans-[12]annulene.
AB  - [reaction: see text] Automerization in tri-trans-[12]annulene (1) was
      investigated by DFT, MP2, and coupled-cluster methods. Using the highest level of
      theory employed here, CCSD(T)/cc-pVDZ//BHandHLYP/6-311+G(d,p), we located two low
      energy pathways for degenerate conformational change from the lowest-energy
      conformer of 1 (1a): one with E(a) = 4.5 kcal/mol that interconverts the three
      inner trans hydrogens with the three outer trans hydrogens and one with E(a) =
      2.7 kcal/mol that interconverts the three inner hydrogens with each other. These
      results are consistent with the experimental results of Oth and co-workers on
      [12]annulene 1a (Oth, J. F. M.; Rottele, H.; Schroder, G. Tetrahedron Lett. 1970,
      61). The conformational exchange of the inner trans hydrogens with the outer ones
      is predicted to occur via a one-step process involving a C(2)-symmetric
      transition state and not via the D(3)-symmetric transition state (1b) that was
      postulated earlier. Conformer 1b was found to be a shallow minimum 6.7 kcal/mol
      above 1a with a barrier of 0.4 kcal/mol for conversion to 1a. Finally, GIAO
      B3LYP/6-311+G(d,p) and BHandHLYP/6-311+G(d,p) computed (1)H NMR chemical shifts
      of 1a and three other low-lying isomers support Oth's original assignment of
      observed (1)H NMR peaks to 1a at both low and high temperature.

PMID- 15844998
TI  - Theoretical study on the isomerization behavior between alpha,beta-unsaturated
      acyl radicals and alpha-ketenyl radicals.
AB  - [reaction: see text] Ab initio calculations using 6-311G**, cc-pVDZ, aug-cc-pVDZ,
      and a (valence) double-zeta pseudopotential (DZP) basis set, with (QCISD,
      CCSD(T)) and without (UHF) the inclusion of electron correlation, and density
      functional methods (BHandHLYP, B3LYP) predict that alpha,beta-unsaturated acyl
      radicals and alpha-ketenyl radicals exist as isomers. At the CCSD(T)/cc
      pVDZ//BHandHLY/cc-pVDZ level of theory, energy barriers of 15.1 and 17.7-21.7 kJ
      mol(-)(1) are calculated for the isomerization of s-trans-propenoyl and s-trans
      crotonoyl radical to ketenylmethyl and 1-ketenylethyl radical, respectively.
      Similar results are obtained for the reactions of s-trans isomers involving
      silyl, germyl, and stannyl groups with energy barriers (DeltaE++) of 12.2-12.4,
      13.1-13.9, and 12.9-18.2 kJ mol(-)(1) at the CCSD(T)/DZP//BHandHLYP/DZP
      calculation, respectively. These results suggest that alpha,beta-unsaturated acyl
      radicals and alpha-ketenyl radicals are not canonical forms but are isomeric
      species that can rapidly interconvert.

PMID- 15844999
TI  - Total syntheses of Yingzhaosu A and of its C(14)-epimer including the first
      evaluation of their antimalarial and cytotoxic activities.
AB  - [reaction: see text] The molecular structure of the naturally occurring
      antimalarial agent yingzhaosu A (1) is characterized by a 2,3
      dioxabicyclo[3.3.1]nonane system (3a), an allylic alcohol, a homoallylic alcohol,
      and five stereogenic centers. Herein we report on the total synthesis of
      yingzhaosu A (1) in eight steps and 7.3% overall yield starting from (S)-limonene
      (12). To maximize efficacy, the bridged bicyclic endoperoxide molecular core was
      constructed by a multicomponent free-radical domino reaction in which five bonds
      are formed in a single operation. In addition, reaction protocols that are
      compatible with the sensitivity of the peroxide function to strong basic and
      nucleophilic reagents as well as to reducing agents were employed. An intriguing
      step involved the selective hydrogenation of a carbon-carbon double bond in the
      presence of a peroxide and an aldehyde function to give aldehyde peroxide 7. The
      two major synthons (aldehydoperoxide 7 and its complementary five-carbon atom
      unit 35) were linked through a Mukaiyama aldol reaction followed by in situ
      dehydration under mild buffered basic conditions. The carbonyl group in the
      resulting peroxidic enone 39 was stereoselectively reduced with either R-CBS
      catalyst (42b) to give, after in situ desilylation, yingzhaosu A (1) or with S
      CBS catalyst (42a) its C(14)-epimer 40. The first quantitative in vitro and in
      vivo data for the antimalarial activity of yingzhaosu A (1) and its C(14)-epimer
      40 are reported. The C(14)-epiyingzhaosu A (40) exhibits potent cytotoxic
      activity against the KB nasal-pharyngeal cancer cell line in vitro.

PMID- 15845000
TI  - Substituent effects on the ring opening of 2-aziridinylmethyl radicals.
AB  - [reaction: see text] Substituent effects on the ring-opening reactions of 2
      aziridinylmethyl radicals were studied systematically for the first time
      utilizing the ONIOM(QCISD(T)/6-311+G(2d,2p):B3LYP/6-311+G(3df,2p)) method. It was
      found that various substituents on the nitrogen atom had a relatively small
      effect on the ring opening of the 2-aziridinylmethyl radical. A pi-acceptor
      substituent at the C(1) position reduced the energy barrier for C-C cleavage
      dramatically, but it increased the energy barrier for C-N cleavage significantly
      at the same time. When the C(1) substituent is alkyl, the ring opening should
      always strongly favor the C-N cleavage pathway, regardless of whether the N
      substituent is alkyl, aryl, or COR. When the C(1) substituent is CHO (or CO
      alkyl, CO-aryl, or CO-OR but not CO-NR(2)), the ring opening strongly favors the
      C-C cleavage pathway, regardless of whether the N substituent is alkyl, aryl, or
      COR. When the C(1) substituent is aryl (or alkenyl or alkynyl), the ring opening
      should favor the C-C cleavage pathway if the N substituent is alkyl or COR. If
      both the C(1) substituent and the N substituent are aryl, the ring opening should
      proceed via both the C-C and C-N cleavage pathways. The solvent effect on the
      regioselectivity of the ring opening of the 2-aziridinylmethyl radicals was found
      to be very small. The substituent effects on C-C cleavage could be explained
      successfully by the spin-delocalization mechanism. For the substituent effects on
      C-N cleavage, an extraordinary through-bond pi-acceptor effect must be taken into
      account. Furthermore, studies on bicyclic 2-aziridinylmethyl radicals showed that
      the ring strain could also affect the regiochemistry of the ring-opening
      reactions.

PMID- 15845001
TI  - The strength of parallel-displaced arene-arene interactions in chloroform.
AB  - [reaction: see text] Triptycene-derived compounds have been prepared to serve as
      conformational equilibrium reporters for direct measurements of arene-arene
      interactions in the parallel-displaced orientation. A series of such compounds
      bearing arenes with different substituents were synthesized, and the ratios of
      the syn and anti conformers were determined by variable-temperature NMR
      spectroscopy. The syn conformer allows attached arenes to interact with each
      other while the anti conformer does not. The free energies derived from the
      syn/anti ratios in chloroform range from slightly positive (0.2 kcal/mol) to
      considerably negative (-0.98 kcal mol) values. The interactions between the
      arenes bearing electron-donating groups (EDG) are either negligible or slightly
      repulsive, while the interactions between arenes bearing electron-withdrawing
      groups (EWG) are attractive. Intermediate free energy values are obtained for
      those compounds bearing arenes with one EDG and one EWG.

PMID- 15845002
TI  - Star-shaped and linear nanosized molecules functionalized with hexa-peri
      hexabenzocoronene: synthesis and optical properties.
AB  - [structure: see text] A synthetic strategy promising the establishment of a new
      star-shaped and linear polycyclic aromatic hydrocarbons (PAHs) family with
      distinct molecular topologies has been developed. The Sonogashira reaction
      between the iodide derivatives 2a-e and phenylacetylene catalyzed with Pd(0)
      affords 3a-e in high yields. The Diels-Alder and decarbonylation reactions
      between 3a-e and tetraphenylcyclophentadiene following the oxidation by FeCl(3)
      produce the star-shaped and linear PAHs 5a-e containing a five-membered ring. The
      structural analysis and the optical properties of all new compounds are performed
      by a combination of MALDI-TOF mass spectrometry, UV-vis, and fluorescence
      spectrometry. The electronic and photophysical properties are studied by
      orthogonal comparisons of the absorption and fluorescence spectra in THF
      solutions, which not only give insight into the interactions among aromatic
      submoieties in each molecule and the effects of meta-conjugation and para
      conjugation on electronic delocalization, but also indicate effective conjugation
      length variations from oligophenylacetylenes 3a-e to oligophenylene dendrimers 4a
      e and PAHs 5a-e. The star-shaped 5c exhibits the highest aggregation in excited
      states compared with the other four hexa-peri-hexabenzocoronene (HBC)
      derivatives.

PMID- 15845003
TI  - Simple diastereoselectivity of the BF3.OEt2-catalyzed vinylogous Mukaiyama aldol
      reaction of 2-(trimethylsiloxy)furans with aldehydes.
AB  - [reaction: see text] A comprehensive scan of the transition state space for the
      reaction of 2-(trimethylsiloxy)furan and methacrolein (24 combinations) offered a
      satisfactory explanation of the high like diastereoselectivity obtained
      experimentally in the Mukaiyama vinylogous aldol reaction of these and related
      partners. It was determined that the syn-gamma-hydroxyalkylbutenolides are formed
      preferentially following a g(+) orientation of the two reactants with the
      aldehyde in the s-trans conformation. Diastereoselectivity is shown to be caused
      by a combination of subtle effects favoring the formation of the like product.

PMID- 15845004
TI  - Molecular diversity via amino acid derived alpha-amino nitriles: synthesis of
      spirocyclic 2,6-dioxopiperazine derivatives.
AB  - [reaction: see text] Chiral spirocyclic 2,6-dioxopiperazines were synthesized
      from amino acid derived alpha-quaternary alpha-amino nitriles via H(2)SO(4)
      promoted cyano hydration, followed by base-mediated cyclization and N-alkylation.
      This methodology, requiring the previous preparation of the amino nitrile by a
      modified Strecker reaction, was applied to Phe, Trp, Pro, Asp, Glu, and Ser
      derivatives. In the case of the Trp-derived amino nitrile the major product of
      the treatment with H(2)SO(4) was not the expected carboxamide, but a new
      tetracyclic indoline derivative containing the novel heterocyclic system
      hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indole, as a result of a domino
      tautomerization. The treatment of this indoline derivative with refluxing 1 N HCl
      led to a Trp-derived 2,6-dioxopiperazine. The 2,6-dioxopiperazine ring opened
      under the reaction conditions of methyl ester saponification, giving N
      (carboxyalkyl)amino acid derivatives. Therefore, the synthesis of 2,6
      dioxopiperazines containing free carboxylic acids from the respective methyl
      esters required transesterification to benzyl esters, followed by hydrogenolysis.

PMID- 15845005
TI  - Novel behavior of O-methylated beta-cyclodextrins in inclusion of meso
      tetraarylporphyrins.
AB  - [structure: see text] The mechanism for formation of extremely stable 1:2
      inclusion complexes of water-soluble meso-tetraarylporphyrins with heptakis(2,3,6
      tri-O-methyl)-beta-cyclodextrin (TMe-beta-CD) in aqueous solutions has been
      studied by means of NMR spectroscopy and isothermal titration calorimetry. To
      simplify the system, 5,10,15-tris(3,5-dicarboxylatophenyl)-20-phenylporphyrin (1)
      was used as a guest porphyrin, because 1 forms only a 1:1 inclusion complex with
      cyclodextrin (CD). As host compounds, native beta-CD and the O-methylated-beta
      CDs such as heptakis(2,3-di-O-methyl)- (2,3-DMe-beta-CD), heptakis(2,6-di-O
      methyl)- (2,6-DMe-beta-CD), and TMe-beta-CDs were used. The thermodynamic
      parameters for complexation such as binding constants (K) and enthalpy (DeltaH
      degrees ) and entoropy changes (DeltaS degrees ) were determined by means of
      isothermal titration calorimetry. The K value for complexation of 1 with CD
      increases in the order beta-CD (K = (1.2 +/- 0.1) x 10(3) M(-)(1)) < 2,6-DMe-beta
      CD ((1.2 +/- 0.1) x 10(4) M(-)(1)) << TMe-beta-CD ((6.9 +/- 0.4) x 10(6) M(-)(1))
      < 2,3-DMe-beta-CD ((8.5 +/- 0.5) x 10(6) M(-)(1)), indicating participation of
      the secondary OCH(3) groups in extremely strong complexation of 1 with CD.
      Complex formation of 1 with beta-CD and 2,6-DMe-beta-CD is an enthalpically and
      entropically favorable process, while that with TMe-beta-CD and 2,3-DMe-beta-CD
      is an enthalpically much more favorable but an entropically less favorable
      process. The thermodynamic parameters suggest that inclusion of 1 into the
      cavities of TMe-beta-CD and 2,3-DMe-beta-CD is promoted by van der Waals
      interactions, which are stronger than those in the cases of beta-CD and 2,6-DMe
      beta-CD. (13)C NMR spectra show that the conformations of both TMe-beta-CD and
      2,3-DMe-beta-CD are altered upon inclusion of 1, while those of beta-CD and 2,6
      DMe-beta-CD are mostly retained. On the basis of these results, it can be
      concluded that induced-fit type complexation of 1 with TMe-beta-CD and 2,3-DMe
      beta-CD causes extremely strong binding of the host to the guest.

PMID- 15845006
TI  - N-Alkenyl-2-aziridinylmethyl radicals and N-alkenylaminyl radicals in cascade
      cyclizations to pyrrolizidines and indolizidines.
AB  - [reaction: see text] The radical cascade cyclizations of N-alkenyl-2
      aziridinylmethyl radicals to pyrrolizidines and indolizidines were examined using
      density functional theory (DFT) calculations. A large preference for cyclization
      to pyrrolizidines was found. These predictions corroborated very well with
      experimental results, leading to an efficient synthesis of pyrrolizidines. No
      radical cascade cyclization to indolizidines could be performed in practice as
      only ring opening of N-alkenyl-2-aziridinylmethyl radicals to N-allyl-N
      alkenylamines occurred.

PMID- 15845007
TI  - AuBr3- and Cu(OTf)2-catalyzed intramolecular [4 + 2] cycloaddition of tethered
      alkynyl and alkenyl enynones and enynals: a new synthetic method for
      functionalized polycyclic hydrocarbons.
AB  - [reaction: see text] Treatment of tethered alkynyl enynones 8, in which a carbon
      chain is attached to the carbonyl group, with a catalytic amount of AuBr(3) in
      (ClCH(2))(2) gave the naphthyl ketones 9 in good to high yields (top-down
      approach). Analogously, the AuBr(3)-catalyzed benzannulations of 10, in which a
      carbon tether is extended from the alkynyl terminus, also proceeded smoothly, and
      the cyclized naphthyl ketones 11 were obtained in high yields (bottom-up
      approach). Similarly, when two kinds of tethered alkenyl enynones 12 and 14 were
      treated with Cu(OTf)(2) catalyst, the corresponding dihydronaphthyl ketone
      products 13 and 15 were obtained in high yields, respectively. The present formal
      [4 + 2] intramolecular cycloaddition proceeds most probably through the
      coordination of the triple bond at the ortho position of substrates to Lewis
      acids, the formation of benzopyrylium ate complex 16 via the nucleophilic
      addition of the carbonyl oxygen atom, the reverse electron demand type Diels
      Alder addition of the tethered alkynes or alkenes to the ate complex, and
      subsequent bond rearrangement.

PMID- 15845008
TI  - Synthesis of photoactivatable acyclic analogues of the lobatamides.
AB  - [structure: see text] The lobatamides and related salicylate enamide natural
      products are potent mammalian V-ATPase inhibitors. To probe details of binding of
      the lobatamides to mammalian V-ATPase, three photoactivatable analogues bearing
      benzophenone photoaffinity labels have been prepared. The analogues were designed
      on the basis of a simplified acyclic analogue 2. Late-stage installation of the
      enamide side chain and tandem deallylation/amidation were employed in synthetic
      routes to these derivatives. Simplified analogue 2 showed strong inhibition
      against bovine clathrin-coated vesicle V-ATPase (10 nM). Analogues 3-5 were also
      evaluated for inhibition of bovine V-ATPase in order to select a suitable
      candidate for future photoaffinity labeling studies.

PMID- 15845009
TI  - Intramolecular interactions between chalcogen atoms: organoseleniums derived from
      1-bromo-4-tert-butyl-2,6-di(formyl)benzene.
AB  - [structure: see text] The synthesis and characterization of a series of low
      valent organoselenium compounds derived from 1-bromo-4-tert-butyl-2,6
      di(formyl)benzene (22) is described. The synthesis of diselenide 25 was achieved
      by the lithiation route whereas bis(4-tert-butyl-2,6-di(formyl)phenyl) diselenide
      (26) was synthesized by treating 22 with disodium diselenide. A series of
      monoselenides (27, 28, and 29) was obtained by facile nucleophilic substitution
      of bromine in 22, using the corresponding selenolates as nucleophiles. The
      halogenation reactions of bis(4-tert-butyl-2,6-di(formyl)phenyl) diselenide (26)
      did not afford the corresponding selenenyl halides but resulted in the isolation
      of an unexpected cyclic selenenate ester 34 as a product. The selenide 32 was
      synthesized by the treatment of dimethoxymethyl diselenide with trilithiated 2
      bromo-5-tert-butyl-N,N'-di(phenyl)isophthalamide. The existence of potential
      Se...O intramolecular nonbonding interactions was examined by IR, (1)H, and
      (77)Se NMR spectroscopy, X-ray crystallography, and computational studies. The X
      ray crystal structures of 26 and 27, having two ortho formyl groups, reveal the
      absence of any Se...O interactions. However, the Se...O interactions were
      observed in the selenenate ester 34 where one of the formyl groups has been
      utilized for the selenenate ring formation. The crystal structures of 26 and 27
      exhibited intermolecular short-range C-H...Se interactions (hydrogen bonding).
      Although there are four heteroatoms in carbamoyl moieties ortho to selenium
      capable of forming a five-membered ring on intramolecular coordination, no such
      intramolecular Se...X (X = N, O) interaction was observed in the crystal
      structure of 32. The density functional theory calculations at the B3LYP/6-31G*
      level predicted that for all the diformyl systems (47a-c, 48a-c), the anti,anti
      conformer (when both formyl oxygen atoms point away from the selenium) is more
      stable. This preference was found to be reversed in the monoformyl-substituted
      systems (50a,b, 51a,b), where the syn conformer (when formyl oxygen is near the
      selenium) is energetically more favorable than the anti conformer.

PMID- 15845010
TI  - Hammett correlation of nornicotine analogues in the aqueous aldol reaction:
      implications for green organocatalysis.
AB  - [reaction: see text] A series of meta- and para-substituted 2-arylpyrrolidines
      were synthesized and examined for their ability to catalyze an aqueous aldol
      reaction under buffered conditions. Kinetic analysis of arylpyrrolidine-catalyzed
      reactions displayed a linear Hammett correlation with rho = 1.14 (R(2) = 0.996),
      indicating that the reaction is accelerated by electron-withdrawing aryl rings.
      These results show promise for the development of a synthetically viable aqueous
      organo-catalyst.

PMID- 15845011
TI  - A three-component photoreversible tag for thiols.
AB  - [structure: see text] A one-pot coupling of a 1,3-diketone, an aldehyde, and an
      alkanethiol has been developed to produce a protected sulfide. Through use of an
      o-nitrophenylbenzaldehyde, this method provides a one-step route to a
      photochemically reversible thiol-protecting group. The kinetics of photolysis
      were established using (1)H NMR analysis, which allows for the rate to be based
      on the entire reaction scheme.

PMID- 15845012
TI  - Asymmetric Henry reaction catalyzed by C2-symmetric tridentate bis(oxazoline) and
      bis(thiazoline) complexes: metal-controlled reversal of enantioselectivity.
AB  - [reaction: see text] C(2)-symmetric tridentate bis(oxazoline) and bis(thiazoline)
      ligands with a diphenylamine backbone have been investigated in the catalytic
      asymmetric Henry reaction of alpha-keto esters with different Lewis acids. Their
      Cu(OTf)(2) complexes furnished S enantiomers, while Et(2)Zn complexes afforded R
      enantiomers, both of them with higher enantioselectivities (up to 85% ee).
      Reversal of enantioselectivity in asymmetric Henry reactions was achieved with
      the same chiral ligand by changing the Lewis acid center from Cu(II) to Zn(II).
      The results show that the NH group in C(2)-symmetric tridentate chiral ligands
      plays a very important role in controlling both the yields and enantiofacial
      selectivity of the Henry products.

PMID- 15845013
TI  - Light, medium, and heavy fluorous triarylphosphines exhibit comparable
      reactivities to triphenylphosphine in typical reactions of triarylphosphines.
AB  - [reaction: see text] The relative reactivities of triphenylphosphine (PPh(3)) and
      three fluorous triarylphosphines [(p-R(F)(CH(2))(2)C(6)H(4))(n)PPh(3)(-)(n),
      where n = 1-3] have been compared in internal competition experiments. Product
      ratios were determined by (31)P NMR spectroscopy. The four phosphines have about
      the same reactivities in oxidation, alkylation, and Staudinger reactions and give
      comparable yields in a preparative Mitsunobu reaction. Previously observed rate
      and yield differences in Staudinger reactions of the fluorous phosphines are
      attributed to solubility effects, not reactivity differences. A light fluorous
      phosphine [(p-C(8)F(17)(CH(2))(2)C(6)H(4))PPh(2)] outperforms a commercially
      available resin-bound phosphine in a competitive benzylation experiment by a
      factor of about 4.

PMID- 15845014
TI  - Reversed approach to S-farnesylation and S-palmitoylation: application to an
      efficient synthesis of the C-terminus of lipidated human N-ras hexapeptide.
AB  - [reaction: see text] A general reversed approach is described to synthesize S
      palmitoylated and S-farnesylated peptides via S(N)2 displacement of bromide by
      reaction of a thiol group containing lipid as nucleophile with bromoalanine
      containing peptides as electrophile. By employing this approach, lipidated
      peptides, including characteristic partial structures of human Ras peptides, were
      synthesized in good yields. This method gives access to farnesylated,
      palmitoylated, and doubly lipidated peptides.

PMID- 15845015
TI  - N6-Arylation of 2'-deoxyadenosine via copper-catalyzed direct coupling with aryl
      halides.
AB  - [reaction: see text] A general method for efficient N(6)-arylation of 2'
      deoxyadenosine via copper-catalyzed direct coupling with aryl iodides and
      bromides is described. The method is useful for aryl halides with either electron
      donating or electron-withdrawing groups.

PMID- 15845016
TI  - A rapid synthesis of 2-aryl-5-substituted-2,3-dihydrobenzofurans.
AB  - [reaction: see text] An effective strategy has been developed for the rapid and
      efficient one-pot synthesis of 2-aryl-5-substituted-2,3-dihydrobenzofurans from
      readily available o-nitrotoluenes and aromatic aldehydes. This strategy allows
      access to a structurally diverse array of products for further manipulation.

PMID- 15845017
TI  - Single and double Suzuki-Miyaura couplings with symmetric dihalobenzenes.
AB  - [reaction: see text] m- or p-Diiodobenzene undergoes selective double coupling
      reactions with arylboronic acids and esters. Selectivity for double coupling over
      single coupling is remarkably strong: even with a diiodobenzene:monoboronic acid
      ratio of 10:1, the products of double coupling are formed in good yields. Steric
      hindrance and electronic influences of the boronic acid or ester, and reaction
      conditions do not appear to impact significantly upon the outcome of the
      reaction. In contrast, m- and p-dibromobenzenes undergo single couplings with
      aryl boronic acids with high selectivity.

PMID- 15845018
TI  - Copper-catalyzed asymmetric ring opening of oxabicyclic alkenes with Grignard
      reagents.
AB  - [reaction: see text] Simple Grignard reagents were applied in copper-catalyzed
      asymmetric ring-opening reactions of oxabenzonorbornadiene derivatives using
      spiro phosphoramidite ligands. Excellent anti-stereoselectivities and good
      enantioselectivities were achieved.

PMID- 15845019
TI  - Enzymatic removal of carboxyl protecting groups. 1. Cleavage of the tert-butyl
      moiety.
AB  - [reaction: see text] A recent discovery that a certain amino acid motif (GGG(A)X
      motif) in lipases and esterases determines their activity toward tertiary
      alcohols prompted us to investigate the use of these biocatalysts in the mild and
      selective removal of tert-butyl protecting groups in amino acid derivatives and
      related compounds. An esterase from Bacillus subtilis (BsubpNBE) and lipase A
      from Candida antarctica (CAL-A) were identified as the most active enzymes, which
      hydrolyzed a range of tert-butyl esters of protected amino acids (e.g., Boc-Tyr
      O(t)Bu, Z-GABA-O(t)Bu, Fmoc-GABA-O(t)Bu) in good to high yields and left Boc, Z,
      and Fmoc-protecting groups intact.

PMID- 15845020
TI  - A tandem Heck-carbocyclization/Suzuki-coupling approach to the stereoselective
      syntheses of asymmetric 3,3-(diarylmethylene)indolinones.
AB  - [reaction: see text] An efficient and versatile method for stereoselective
      synthesis of (E)-3,3-(diarylmethylene)indolinones by a palladium-catalyzed tandem
      Heck-carbocyclization/Suzuki-coupling sequence is presented. Factors influencing
      yield and selectivity, namely catalyst, coordinating ligand, and solvent, are
      detailed.

PMID- 15845021
TI  - Enantioselective total synthesis of (-)-curcuquinone via regioselective chromium
      mediated benzannulation.
AB  - [reaction: see text] A short and efficient, high-yielding enantioselective total
      synthesis of the marine natural product (-)-curcuquinone 1 is reported involving
      a regioselective [3 + 2 + 1]-benzannulation reaction as the key step.
      Additionally, this strategy allows the isolation of curcuhydroquinone monomethyl
      ether 9 as an intermediate of the benzannulation reaction and its subsequent
      further protection toward diversified hydroquinones.

PMID- 15845022
TI  - Enantioselective syntheses of (+)-xylarenal A and ent-xylarenal A.
AB  - [reaction: see text] The total synthesis of the sesquiterpenoid xylarenal A is
      reported. This first synthetic entry to an eremophilane terpenoid with an
      exocyclic vinyl aldehyde unit involves the use of the bicyclic enone (+)-3, which
      after a gamma-oxidation and alpha'-allylation leads to the formation of the
      ketone (+)-8. After its acylation, an oxidative cleavage of the allyl side chain
      followed by alpha-methylenation of the resulting aldehyde gives (+)-xylarenal A
      (1). The synthesis of (-)-xylarenal A from (-)-3 is also reported. Moreover, the
      first total synthesis of the trinoreremophilane (+)-1alpha-hydroxyisoondetianone
      (5) is described.

PMID- 15845023
TI  - Sulfur-based protecting groups for pyrroles and the facile deprotection of 2-(2,4
      dinitrobenzene)sulfinyl and sulfonyl pyrroles.
AB  - [reaction: see text] The effectiveness of simple sulfinyl and sulfonyl groups as
      electron-withdrawing protecting groups for pyrroles has been analyzed using (13)C
      NMR spectroscopy and confirmed by consideration of X-ray crystal structures.
      Additionally, the 2,4-dinitrobenzenesulfinyl and sulfonyl groups are shown to be
      effective electron-withdrawing protecting groups for pyrroles, and they can be
      removed by treatment with benzene thiol or thiolate under mild and specific
      conditions.

PMID- 15845024
TI  - A catalytic enantioselective hetero Diels-Alder approach to the C20-C32 segment
      of the phorboxazoles.
AB  - [reaction: see text] An efficient synthesis of the C20-C32 segment of the
      phorboxazoles has been achieved using an enantioselective hetero Diels-Alder
      reaction catalyzed by Jacobsen's Cr(III) amino indanol Schiff base catalyst.

PMID- 15845025
TI  - Template effect of tetrathiafulvalene in the formation of cyclobis(paraquat-p
      phenylene).
AB  - [reaction: see text] The template effect exerted by tetrathiafulvalene (TTF) in
      the ring-closure reaction of the trication 5(3+) yielding cyclobis(paraquat-p
      phenylene) has been quantitatively evaluated in acetonitrile at 62 degrees C with
      UV-vis spectrophotometry. The rate of ring closure of the trication 5(3+) largely
      increases in the presence of the template (a maximum increase of ca. 80 times at
      [TTF] approximately 0.14 M). The results are compared with those of other
      aromatic templates, 2 and 3, that were provided with polyethereal sidearms and
      indicate that the template ability of tetrathiafulvalene is comparable or better
      than that of the others.

PMID- 15845027
TI  - Surface salt bridges modulate the DNA site size of bacterial histone-like HU
      proteins.
AB  - Bacterial histone-like DNA-binding proteins are best known for their role in
      compacting the genomic DNA. Of these proteins, HU is ubiquitous and highly
      conserved across the eubacterial kingdom. Using the HBsu (Bacillus subtilis
      encoded HU homologue) as a model, we explore here the molecular basis for the
      ability of some HU homologues to engage a longer approx. 35 bp DNA site as
      opposed to the much shorter sites reported for other homologues. Using
      electrophoretic mobility-shift assays, we show that the DNA site size for HBsu is
      approx. 10-13 bp and that a specific surface salt bridge limits the DNA site size
      for HBsu. Surface exposure of the highly conserved Lys3, achieved by substitution
      of its salt-bridging partner Asp26 with Ala, leads to enhanced DNA compaction by
      HBsu-D26A (where D26A stands for the mutant Asp26-->Ala), consistent with the
      interaction of Lys3 with the ends of a 25 bp duplex. Both HBsu and HBsu-D26A bend
      DNA, as demonstrated by their equivalent ability to promote ligase-mediated DNA
      cyclization, indicating that residues involved in mediating DNA kinks are
      unaltered in the mutant protein. We suggest that Lys3 is important for DNA
      wrapping due to its position at a distance from the DNA kinks where it can exert
      optimal leverage on flanking DNA and that participation of Lys3 in a surface salt
      bridge competes for its interaction with DNA phosphates, thereby reducing the
      occluded site size.

PMID- 15845028
TI  - Nucleotide sequence analyses of human complement 6 (C6) gene suggest balancing
      selection.
AB  - The sixth complement component (C6) has a common charge polymorphism, C6A and
      C6B, with similar gene frequencies in all major populations. In addition, C6B2 is
      also found in Japanese populations at a frequency of about 6%. Sequence analyses
      of the coding region of three human and ape C6 alleles indicated four
      nonsynonymous and three synonymous changes in C6*B2 relative to C6*A, suggesting
      that a recombination event occurred between C6*B2 and C6*A to give rise to C6*B.
      Sequence variation in a 3.86 kb region encompassing exon 3, where the causal base
      change of the common C6 polymorphism is found, indicated that several single
      nucleotide polymorphisms (SNPs) were in extensive linkage disequilibrium (LD),
      with little differentiation among populations. Sliding window estimates of two
      test statistics for neutrality revealed significant values in a subregion where
      the replacement coding polymorphism resides, in all three human populations.
      These results raise the possibility that the two common C6 alleles in human
      populations are maintained by balancing selection.

PMID- 15845026
TI  - Exploring the functions of RNA interference pathway proteins: some functions are
      more RISCy than others?
AB  - PPD (PAZ Piwi domain) proteins and the Dicer family have been the subjects of
      intense study over the last 6 years. These proteins have well-established roles
      in RNAi (RNA interference), a process that relies on siRNAs (small interfering
      RNAs) or miRNAs (microRNAs) to mediate specificity. The development of techniques
      for applying RNAi as a laboratory tool and a molecular therapeutic technique has
      rapidly outpaced our understanding of the biology of this process. However, over
      the last 2 years, great strides have been made towards elucidating how PPD
      proteins and Dicer regulate gene-silencing at the pre- and post-transcriptional
      levels. In addition, evidence is beginning to emerge that suggests that these
      proteins have additional siRNA-independent roles as cell-cycle regulators. In the
      present review, we summarize the well-known roles of these two classes of
      proteins in gene-silencing pathways, as well as explore the evidence for novel
      roles of PPD and Dicer proteins.

PMID- 15845029
TI  - Analysis of dystrophin gene deletions indicates that the hinge III region of the
      protein correlates with disease severity.
AB  - We have investigated the frequency of deletions in the dystrophin gene in 108
      unrelated Duchenne and Becker muscular dystrophy (DMD/BMD) patients from southern
      Italy (DMD, n. 47; BMD, n. 61) and identified 89 deletions. The de novo mutation
      rate (about 30%), and the preferentially maternal origin of deletional mutations,
      analysed in families in which the maternal grandparents were available or their
      haplotypes could be unequivocally reconstructed, are in agreement with data
      reported for other populations. The correlation between BMD phenotype and type of
      deletion suggests that, in the distal rod domain region, the deletion size may
      not be as crucial as the particular combination of missing exons. In fact, we
      provide immunohistochemical and clinical evidence that in-frame deletion of the
      hinge III region in the distal rod domain results in a milder phenotype as
      compared with shorter deletions that do not include the hinge III region. Our
      data obtained in BMD patients, by confirming inferences arising from minigene
      transfection experiments in mdx mice, represent an important contribution to gene
      therapy approaches.

PMID- 15845030
TI  - Simultaneous selection of the wild-type genotypes of the G894T and 4B/ 4A
      polymorphisms of NOS3 associate with high-altitude adaptation.
AB  - The routine performance of high-altitude (HA) natives in the hypoxic environment
      of HA exemplifies the process of adaptation mainly through natural selection. The
      recent therapeutic application of nitric oxide (NO) in HA disorders, for the
      improvement of oxygenation and vasodilation, ushered us to investigate the
      endothelial nitric oxide synthase gene (NOS3) with respect to HA adaptation. The
      study subjects, 131 HA monks (HAM), 136 HA controls (HAC), and 170 lowlanders
      (LLs) were screened for NOS3 G894T (Glu298Asp) and 4B/4A polymorphisms. The NO
      levels were estimated, for a correlation with the polymorphisms. The three groups
      were in Hardy-Weinberg equilibrium for the polymorphisms. The overall genotype
      distributions for the G894T and 4B/4A polymorphisms were significant (P = 0.01
      and 0.02, respectively) in the three groups. Wild-type alleles G and 4B were
      significantly over-represented in the HA groups as compared to the LLs (P = 0.006
      and P = 0.02, respectively). The NO levels were in the order of HAM>HAC>LLs (P <
      0.0001). Furthermore, combinations of the GG and BB genotypes were distributed
      significantly more frequently in the HAM (P < 0.0001) and HAC (P = 0.0005) than
      in LLs. The NO levels contributed by the wild-type genotype combination GG, BB
      were significantly elevated when compared with the remaining eight genotype
      combinations together in the HAM, HAC and LLs (P = 0.003, P = 0.0006 and P <
      0.0001, respectively). To conclude, the genotype combination of NOS3 wild-type
      homozygotes (GG, BB) was found significantly more frequently in HA groups than in
      LLs, by contributing to higher NO levels associated with HA adaptation.

PMID- 15845031
TI  - Wilson disease: high prevalence in a mountainous area of Crete.
AB  - Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The
      disorder is caused by mutations in the ATP7B gene, encoding a copper transporting
      P-type ATPase. The worldwide incidence is in the order of 30 cases per million,
      with a gene frequency of 0.56% and a carrier frequency of 1 in 90. The increased
      number of Wilson disease patients in the island of Crete led us to study the
      spectrum of mutations in a small village close to the city of Heraklion, from
      where many patients have been referred during the last 25 years. In order to
      estimate the frequency of the disease, we firstly investigated the number of
      births and the number of WD patients in the village since 1978. Six out of 90
      births were diagnosed as WD patients, presenting the highest prevalence of WD
      reported so far. Analysis of the whole gene in three Wilson disease patients, and
      relatives of a boy who died from WD, led to the detection of 4 different point
      mutations. Two of them were missense (p.I1148T and p.G1176R) and cosegregated in
      cis in the same patient; the other allele of this patient carried a nonsense
      mutation (p.Q289X). This is the first report in the literature of three mutations
      co-segregating in the same WD patient. The fourth mutation identified was a novel
      frameshift mutation (c.398delT) with documented cosegregation. When screening 200
      inhabitants originating from the same area, 18 were found to be carriers of one
      of these mutations. These findings indicate the need for health education
      intervention, genetic counselling and newborn screening for the Wilson disease.

PMID- 15845032
TI  - Ethiopia: between Sub-Saharan Africa and western Eurasia.
AB  - Ethiopia is central to population genetic studies investigating the out of Africa
      expansion of modern humans, as shown by Y chromosome and mtDNA studies. To
      address the level of genetic differentiation within Ethiopia, and its
      relationship to Sub-Saharan Africa and Eurasia, we studied an 8 kb segment of the
      X-chromosome from 72 chromosomes from the Amhara, Oromo and Ethiopian Jews, and
      compared these results with 804 chromosomes from Middle Eastern, African, Asian
      and European populations, and 22 newly typed Saharawi. Within Ethiopia the two
      largest ethnic groups, the Amhara and Oromo, were not found to be statistically
      distinct, based on an exact test of haplotype frequencies. The Ethiopian Jews
      appear as an admixed population, possibly of Jewish origin, though the data
      remain equivocal. There is evidence of a close relationship between Ethiopian and
      Yemenite Jews, likely a result of indirect gene flow. Within an African and
      Eurasian context, the distribution of alleles of a variable T(n) repeat, and the
      spread of haplotypes containing Africa-specific alleles, provide evidence of a
      genetic continuity from Sub-Saharan Africa to the Near East, and furthermore
      suggest that a bottleneck occurred in Ethiopia associated with an out of Africa
      expansion. Ethiopian genetic heterogeneity, as evidenced by principal component
      analysis of haplotype frequencies, most likely resulted from periods of
      subsequent admixture. While these results are from the analysis of one locus, we
      feel that in association with data from other marker systems they add a
      complementary perspective on the history of Ethiopia.

PMID- 15845033
TI  - The effect of genetic drift in a young genetically isolated population.
AB  - The genetic make-up of genetically isolated populations may differ from a general
      population as a result of genetic drift and founder effects. We assessed the
      extent of this deviation in a recently isolated population located in the
      southwest of the Netherlands and studied as part of the Genetic Research in
      Isolated Population (GRIP) program. A gene-dropping experiment was performed in a
      large pedigree from this isolate, assuming different initial frequencies in the
      population founders came from. Allelic frequencies in the last generations of
      this pedigree were estimated. Simulation analysis showed large fluctuations, as
      measured by variation coefficient and sufficient loss probability, when initial
      frequencies were lower than or equal to 1%. For initial frequencies larger than
      1% the fluctuations were small. We also analyzed mean heterozygosity and allele
      diversity of 592 markers in a random sample from the GRIP population. The results
      were compared with a general population (CEPH sample), old large isolate
      (Icelandic sample) and the small-sized population of Talana (Sardinia). GRIP mean
      heterozygosity and mean number of alleles were significantly lower as compared
      with CEPH and Iceland, but much higher when compared with the Talana population.
      We also concluded that the findings from the GRIP population for common variants
      (>1%) are likely to be extendable to other young isolates in Europe as well as to
      outbred populations.

PMID- 15845034
TI  - Power and related statistical properties of conditional likelihood score tests
      for association studies in nuclear families with parental genotypes.
AB  - Both population based and family based case control studies are used to test
      whether particular genotypes are associated with disease. While population based
      studies have more power, cryptic population stratification can produce false
      positive results. Family-based methods have been introduced to control for this
      problem. This paper presents the full likelihood function for family-based
      association studies for nuclear families ascertained on the basis of their number
      of affected and unaffected children. The likelihood of a family factors into the
      probability of parental mating type, conditional on offspring phenotypes, times
      the probability of offspring genotypes given their phenotypes and the parental
      mating type. The first factor can be influenced by population stratification,
      whereas the latter factor, called the conditional likelihood, is not. The
      conditional likelihood is used to obtain score tests with proper size in the
      presence of population stratification (see also Clayton (1999) and Whittemore &
      Tu (2000)). Under either the additive or multiplicative model, the TDT is known
      to be the optimal score test when the family has only one affected child. Thus,
      the class of score tests explored can be considered as a general family of TDT
      like procedures. The relative informativeness of the various mating types is
      assessed using the Fisher information, which depends on the number of affected
      and unaffected offspring and the penetrances. When the additive model is true,
      families with parental mating type Aa x Aa are most informative. Under the
      dominant (recessive) model, however, a family with mating type Aa x aa(AA x Aa)
      is more informative than a family with doubly heterozygous (Aa x Aa) parents.
      Because we derive explicit formulae for all components of the likelihood, we are
      able to present tables giving required sample sizes for dominant, additive and
      recessive inheritance models.

PMID- 15845035
TI  - A dominant form of congenital stationary night blindness (adCSNB) in a large
      Chinese family.
AB  - Summary A pedigree of congenital stationary night blindness (CSNB) is described
      in a large Chinese family. The clinical description, pedigree, dark adaptation
      and elctroretinogram (ERG) studies indicate that the patients have an autosomal
      dominant form (ad) of CSNB. The disorder has been transmitted through at least 12
      generations with over 40 affected individuals identified. The ERG data reveal
      that affected persons have severely diminished b-wave responses to dim light, but
      normal a-wave and subnormal b-wave responses to maximum light stimuli. The dark
      adaptation curves of three patients show a monophase curve, typical for night
      blindness. We have excluded the five previously known mutations in the three
      genes (RHO, PDE6B and GNAT1) associated with adCSNB, and linkage studies have
      excluded tight linkage between the disease locus and markers associated with
      these three genes. Thus, this family has adCSNB caused by a different gene from
      the previously identified RHO, PDE6B, and GNAT1.

PMID- 15845036
TI  - Application of the stepwise focusing method to optimize the cost-effectiveness of
      genome-wide association studies with limited research budgets for genotyping and
      phenotyping.
AB  - The recent cataloguing of a large number of SNPs enables us to perform genome
      wide association studies for detecting common genetic variants associated with
      disease. Such studies, however, generally have limited research budgets for
      genotyping and phenotyping. It is therefore necessary to optimize the study
      design by determining the most cost-effective numbers of SNPs and individuals to
      analyze. In this report we applied the stepwise focusing method, with two-stage
      design, developed by Satagopan et al. (2002) and Saito & Kamatani (2002), to
      optimize the cost-effectiveness of a genome-wide direct association study using a
      transmission/disequilibrium test (TDT). The stepwise focusing method consists of
      two steps: a large number of SNPs are examined in the first focusing step, and
      then all the SNPs showing a significant P-value are tested again using a larger
      set of individuals in the second focusing step. In the framework of optimization,
      the numbers of SNPs and families and the significance levels in the first and
      second steps were regarded as variables to be considered. Our results showed that
      the stepwise focusing method achieves a distinct gain of power compared to a
      conventional method with the same research budget.

PMID- 15845037
TI  - Integrating case-control and TDT studies.
AB  - Genetic-association studies are widely expected to unravel the genetic basis of
      complex diseases. The population-based case-control study, a commonly used
      approach for association studies, is subject to the problem of population
      admixture. Consequently, evidence of disease-marker associations obtained from
      such studies is ideally confirmed by alternative methods. The
      Transmission/Disequilibrium Test (TDT) is suitable to assess evidence of
      association obtained from case-control studies. Since data are increasingly
      available from both case-control and TDT studies of the same disease-marker
      association, it is useful to obtain a combined estimate of disease-marker
      association. The odds ratio is a commonly used measure of the magnitude of a
      disease-marker association that can be easily obtained in case-control studies.
      Here we show how an odds ratio estimate and its' associated standard error can be
      obtained from TDT results. Furthermore, we suggest a method for integrating
      results from case-control studies and the TDT to provide a combined estimate of
      disease-marker association. Such combined estimates can be used to contrast the
      results of the two studies and provides an overall picture of the effect size
      attributable to such polymorphism. An illustrative application is made to a
      published data set on type 2 diabetes.

PMID- 15845040
TI  - Abstracts presented at the 38th Annual Scientific Meeting of the Australasian
      College of Dermatologists, 15-18 May 2005, Perth, Western Australia.

PMID- 15845042
TI  - Synovial osteochondromatosis: the spectrum of imaging findings.
AB  - Imaging plays a vital role in the diagnosis and management of synovial
      osteochondromatosis, a proliferative disorder of the synovium with associated
      loose body formation. The aim of this pictorial review is to illustrate the
      radiographic, computed tomographic and magnetic resonance appearances of various
      stages of the disease.

PMID- 15845043
TI  - Cerebral venous sinus thrombosis presenting as subdural haematoma.
AB  - The authors report a 39-year-old woman who presented with intermittent,
      excruciating nuchal and occipital headache. Magnetic resonance imaging and
      magnetic resonance angiography scans showed bilateral subdural haematomas with
      veno-occlusive disease of the superficial and deep venous systems. There were
      bridging collaterals with scalp veins, bleeds from which could explain the
      subdural haematoma. There was acute on chronic veno-occlusive disease with an
      acute rise in intracranial pressure and a bleed from the vein of Galen.

PMID- 15845044
TI  - Measurement error in computed tomography pelvimetry.
AB  - Computed tomography pelvimetry is still used in clinical practice. We wished to
      quantify observer error in order to assess the level of confidence with which
      pelvic measurements can be described as adequate or inadequate. Anteroposterior
      inlet, anteroposterior outlet, transverse inlet and interspinous distances were
      measured from 11 CT pelvimetry examinations by five observers at one institution.
      Three CT pelvimetries were measured by five observers at a second institution.
      Intraobserver and interobserver variation was assessed using analysis of
      variance. Reliability of measurements was assessed using intraclass correlation
      coefficient. Combined error was calculated to determine 95% confidence limits for
      published minimum recommended pelvic measurements. The standard error of
      measurement, combining all sources, for measurement of the bony dimensions of the
      pelvis were: for anteroposterior inlet, 2.0 mm; anteroposterior outlet, 6.9 mm;
      transverse inlet, 1.3 mm; and interspinous distance, 2.1 mm. The 95% confidence
      interval around the recommended anteroposterior outlet of 100 mm was 88.5-111.3
      mm. Observer variation in measurement of anteroposterior outlet is so large as to
      make the measurement of doubtful clinical utility.

PMID- 15845045
TI  - Outcome following radiotherapy for loco-regionally recurrent non-small cell lung
      cancer.
AB  - Local and regional recurrence of non-small cell lung cancer is reported to occur
      in 13-20% of treatment failures after resection. Reported post-recurrent median
      survival following radiotherapy ranges from 9 to 14 months. This study examines
      survival following radiotherapy alone for patients with loco-regionally recurring
      non-small cell lung cancer after initial surgery. Fifty-five patients, receiving
      radiotherapy at Westmead Hospital between 1979 and 1997, were eligible for study.
      Data were collected retrospectively by reviewing patient records. The end-point
      was overall survival. Symptom control was also recorded. Prognostic factors for
      analysis included age, sex, original presenting stage, disease-free interval
      (DFI), performance status, site of recurrence, treatment intent and dose. The
      median overall survival was 11.5 months (95% confidence interval: 8.1-13.0).
      Survival following treatment with radical intent was 26 months compared to 10.5
      months for patients treated with palliative intent (P = 0.025). There was no
      significant difference in survival for short (< or = 2 years) or long DFI,
      performance status, radiation dose, age, sex, site of recurrence or stage. Most
      patients (55%) had partial or complete resolution of symptoms. Radiotherapy
      results in overall post-recurrence median survival of nearly 1 year, consistent
      with previous published data. Radical treatment intent predicts better prognosis
      as a result of patient selection and higher dose. Radiotherapy is effective at
      palliating symptoms of this disease.

PMID- 15845046
TI  - Ultrasonographic changes in malignant neck nodes during radiotherapy in head and
      neck squamous carcinoma.
AB  - Limited information is available about the sonomorphological changes in
      metastatic neck nodes during radiotherapy. The aim of this study was to evaluate
      the pattern of sonomorphological changes in metastatic neck nodes with
      radiotherapy. The study population consisted of 16 consecutive patients planned
      for radical radiotherapy to the head and neck. All patients were subjected to
      four ultrasound examinations: before therapy, at 46 Gy, at the conclusion of
      radiation and at first follow up. A total of 59 ultrasound examinations were
      performed on 16 patients. The difference between the mean number of nodes
      detected per patient before (10.6) and after (7.8) radiation was significant (P =
      0.05). Sixteen nodes were categorized as malignant at first sonography, half of
      which reverted back to normal by the end of radiation. Changes in the
      sonomorphology of malignant cervical lymph nodes occur with radiotherapy with
      more that half demonstrating reversion to normal pattern. Future studies
      correlating this with histopathology should be considered.

PMID- 15845047
TI  - Genetic counselling following paternal therapeutic irradiation.
AB  - We discuss a patient who received adjuvant radiotherapy for stage I seminoma. He
      was advised to avoid conception for 6 months following treatment. However, his
      partner became pregnant only shortly after he completed his radiotherapy (i.e.
      with sperm that had been irradiated). We estimated the dose received by the
      remaining testis as 30 cGy. Here, we review the information available to advise
      patients on the risks to the fetus from paternal preconception irradiation. For
      the population, a doubling dose for hereditary effects of 1 Gy has recently been
      reaffirmed (United Nations Scientific Committee on the Effects of Atomic
      Radiation 2001). However, a range of animal studies suggest conception with
      postmeiotic sperm carries a greater risk of genetic damage than conception with
      sperm derived from irradiated stem cells. We have attempted to quantify the risks
      in this particular case. Lead shielding of the testes may reduce radiation
      received from the primary beam, but internal scatter still produces a risk. In
      male patients who are potentially fertile, the best advice remains to delay
      conception after radiotherapy for as long as 6 months. Our case illustrates the
      need to reinforce such advice.

PMID- 15845048
TI  - Evaluation of the use of computed tomography versus conventional orthogonal X-ray
      simulation in the treatment of rectal cancer.
AB  - The aim of this study is to compare and contrast the treatment fields designed
      using CT versus conventional orthogonal X-ray simulation in the treatment of
      patients with rectal cancer given preoperative chemotherapy and radiotherapy.
      Nine patients participated in this study. The coverage of treatment fields, the
      volume of treatment fields, and the position of the anorectal junction in
      relation to the inferior border of the obturator foramen as the delineator of the
      pelvic floor were evaluated in each patient using CT and conventional orthogonal
      X-ray simulation. The results demonstrated undercoverage of the anterior border
      of the lateral fields of up to 2.5 cm in seven of nine patients when conventional
      orthogonal X-ray simulation was compared to CT simulation. In addition, the
      inferior border of the obturator foramen proved to be a poor delineator of the
      pelvic floor with the anorectal junction situated up to 2 cm superiorly in seven
      of nine patients. In conclusion, CT simulation is superior to conventional
      orthogonal X-ray simulation when designing treatment fields for patients with
      rectal cancer.

PMID- 15845049
TI  - Pituitary apoplexy: an unusual cause of frontal lobe syndrome.
AB  - Pituitary apoplexy presenting as frontal lobe syndrome is rare. Interestingly, in
      our patient the frontal lobe infarct was as a result of intense anterior cerebral
      artery spasm consequent to nonaneurysmal subarachnoid haemorrhage. The mechanisms
      of cerebral infarct associated with pituitary apoplexy are discussed.

PMID- 15845050
TI  - Castleman's disease with isolated extensive cervical involvement.
AB  - Castleman's disease is a lymphoproliferative disorder of uncertain cause
      characterized by a distinctive pattern of hypervascular lymphoid hyperplasia.
      Computed tomography and MRI can be used to define the extent of disease. The
      latter may be used to detect curvilinear hypointensities within the abnormal
      node. Symmetrical involvement of nasopharyngeal and parapharyngeal regions in our
      case without disease elsewhere is considered to be an unusual presentation.

PMID- 15845051
TI  - Paratubal cyst complicated by tubo-ovarian torsion: computed tomography features.
AB  - Paratubal cysts complicated by tubo-ovarian torsion are an uncommon cause of
      acute right iliac fossa pain in children and very rarely diagnosed accurately
      preoperatively. We report a constellation of diagnostic CT features in a 12-year
      old pubertal girl.

PMID- 15845052
TI  - Transjugular intrahepatic cavoportal shunt for Budd-Chiari syndrome.
AB  - Budd-Chiari syndrome (BCS) is characterized by obstruction of the hepatic venous
      outflow tract. Therapeutic options for BCS are limited. We report a case of a 21
      year-old woman with protein S and C deficiency with gross ascites. Treatment with
      transjugular intrahepatic portosystemic shunt (TIPS) was attempted, which
      revealed occluded hepatic veins, so transcaval TIPS was performed. No serious
      procedure-related complication occurred. After successful shunt creation, the
      patient's symptoms subsided and she was discharged and followed up for 6 months.

PMID- 15845053
TI  - Pyogenic abscess complicating a resolving cerebral haematoma secondary to a
      cavernous haemangioma: computed tomography and magnetic resonance imaging
      findings.
AB  - A case is discussed of a brain abscess complicating an intracerebral haemorrhage
      occurring in a cavernous haemangioma. A young child presented with focal seizures
      as a result of a large intracerebral haemorrhage, occurring in a cavernous
      haemangioma. The only clue to the underlying vascular malformation was the
      presence of an associated developmental venous anomaly. The case was complicated
      by the development of a brain abscess at the site of the intracranial haematoma.
      The CT and MRI findings are discussed.

PMID- 15845054
TI  - Neurenteric cyst of the posterior mediastinum.
AB  - We report a case of a large posterior mediastinal neurenteric cyst in a neonate
      demonstrated by chest radiographs, barium swallow examination, ultrasonography
      and CT of the thorax. All the investigations revealed a large posterior
      mediastinal cystic mass with vertebral anomalies in the form of scoliosis and
      hemivertebra. The cyst was completely excised by a right posterolateral
      thoracotomy and biopsy showed the features of a neurenteric cyst. The rarity of
      the lesion prompted us to report this case.

PMID- 15845055
TI  - Spontaneous calcific cerebral embolus.
AB  - Spontaneous calcific cerebral embolus is a rare complication of calcific vascular
      disease such as calcified aortic plaques, and calcific aortic and mitral
      stenosis. Fewer than 10 case reports are described in the literature. Cerebral
      ischaemic symptoms may provide the indication for surgical replacement, even in
      the absence of valvular insufficiency or stenotic symptoms. We report a case of
      stroke in a young man with a known bicuspid calcific aortic valve.

PMID- 15845056
TI  - Diagnosis of tubular colonic duplication by barium follow-through study.
AB  - Barium enema studies are considered essential for the diagnosis of tubular
      colonic duplication with opacification of two colons being the diagnostic sign.
      Yet in certain cases, barium enema apparently does not show positive findings. A
      case is reported in which a barium follow-through study established the complete
      diagnosis of duplication of colon and terminal ileum. The findings were confirmed
      on laparotomy.

PMID- 15845057
TI  - Primary papillary serous cystadenocarcinoma of broad ligament.
AB  - A rare case of an advanced primary broad ligament carcinoma is discussed, with a
      review of the literature regarding its incidence, presentation and management.
      This patient showed a complete response to adjuvant cisplatin-based chemotherapy
      following panhysterectomy and is presently without any evidence of disease, 15
      months after completion of her treatment.

PMID- 15845058
TI  - Hepatic angiosarcoma: detection with computed tomography.
AB  - Hepatic angiosarcoma is a rare vascular neoplasm which occurs typically in men
      aged between 50 and 70 years. The cause is unknown but previous studies have
      linked several carcinogens to its pathogenesis. A case of advanced multifocal
      hepatic angiosarcoma with splenic metastasis is presented with brief discussion
      of the clinical and histological features. Typical CT features and contrast
      enhancement characteristics are also reviewed.

PMID- 15845059
TI  - Magnetic resonance imaging findings in fatal primary cerebral infection due to
      Chaetomium strumarium.
AB  - This report describes MRI findings of a rare case of biopsy-proven fatal cerebral
      infection with Chaetomium strumarium in a 28-year-old man with a history of i.v.
      drug abuse. Magnetic resonance imaging revealed rapidly progressing lesions with
      irregular peripheral enhancement, possible central haemorrhage and significant
      mass effect. Only six cases of cerebral infection with Chaetomium have been
      reported in the English literature. This is the first report in the radiology
      literature describing the imaging findings. The previously reported cases of
      cerebral infection by the Chaetomium species are also reviewed.

PMID- 15845060
TI  - Double-chambered right ventricle: magnetic resonance imaging findings.
AB  - Primary double-chambered right ventricle is an uncommon congenital anomaly that
      presents with right ventricular outflow tract obstruction in childhood or
      adolescence. A search of the literature revealed only a few documented case
      reports with MRI findings. We present a case with mixed lesions, and with
      anomalous muscle bundles located both in the middle portion of the right
      ventricular sinus and at the subinfundibular level.

PMID- 15845061
TI  - Imaging spectrum in disseminated histoplasmosis: case report and brief review.
AB  - The clinical manifestations of chronic disseminated histoplasmosis are non
      specific and resemble those of other chronic infections and malignancies. We
      report the radiographic, sonographic and contrast-enhanced CT appearances of
      histoplasmosis in an adult male with non-insulin dependent diabetes mellitus, who
      was HIV negative and presented with weight loss and pyrexia. Imaging studies
      simulated tuberculosis with mediastinal lymphadenopathy, bilateral fibrotic lung
      lesions, hepatomegaly and bilateral hypoattenuating adrenal enlargement, without
      clinical or laboratory evidence of hypoadrenalism. Computed tomography-guided
      fine-needle aspiration biopsy of adrenal glands revealed Histoplasma capsulatum.
      We report our experience to increase awareness of the imaging spectrum of
      disseminated histoplasmosis and its similarity to tuberculosis as, with
      increasing incidence of AIDS, the chances of these infections are likely to
      increase. Moreover, awareness of this entity is important because it is known
      that untreated disseminated histoplasmosis is fatal.

PMID- 15845062
TI  - Perihepatitis associated with systemic lupus erythematosus: computed tomography
      findings.
AB  - The imaging findings of a 29-year-old woman with known systemic lupus
      erythematosus, and a clinical presentation and CT appearances consistent with
      perihepatitis are presented.

PMID- 15845063
TI  - Successful medical treatment of abdominal aortic aneurysms in a patient with
      Behcet's disease: imaging findings.
AB  - Arterial manifestations of Behcet's disease consist of aneurysm formation,
      stenosis and occlusion. Aneurysms in Behcet's disease most commonly involve the
      pulmonary arteries and have been shown to resolve with medical treatment.
      However, this regression pattern with medical therapy has not been reported for
      aortic aneurysms to date. We present a 43-year-old man with bilateral abdominal
      aortic aneurysms resulting from Behcet's disease resolving with medical therapy.

PMID- 15845064
TI  - Sclerosing mesenteritis.
AB  - Sclerosing mesenteritis is a rare benign process involving mesenteric fat that
      has non-specific histology and imaging characteristics, which are critical to the
      diagnosis. It has two different pathological variants: mesenteric panniculitis
      (acute or subacute) and retractile mesenteritis (chronic). This case study
      illustrates the radiological findings of sclerosing mesenteritis, describes
      certain signs that suggest the diagnosis and reviews recent published literature.

PMID- 15845065
TI  - Cranial magnetic resonance imaging of Wolfram (DIDMOAD) syndrome.
AB  - Wolfram syndrome is a rare neurodegenerative disorder characterized by diabetes
      insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD). A wide
      spectrum of abnormalities of the central nervous system, urinary tract and
      endocrine glands is also observed. We report cranial MRI findings in a 32-year
      old female patient with Wolfram syndrome. In addition to the classical features,
      including absence of the normal high signal of the neurohypophysis, atrophy of
      visual pathways, the brainstem, cerebellum and cerebral cortex, we observed
      bilateral hyperintensity on proton density- and T2- weighted images related to
      the optic radiations in the periventricular white matter of the temporal and
      parieto-occipital lobes, which may reflect gliosis pathologically.

PMID- 15845066
TI  - Menkes disease: a rare cause of bilateral inguinal hernias.
AB  - This case of Menkes disease presented with the uncommon association of bilateral
      inguinal hernias at the age of 4 months. Further investigation demonstrated
      classical skeletal and neurological changes of this rare neurodegenerative
      disorder.

PMID- 15845067
TI  - Reply: D Leighton--RE: Audit of neonatal scans.

PMID- 15845074
TI  - Translation of an integral membrane protein in distal dendrites of hippocampal
      neurons.
AB  - Maintenance of synaptic plasticity requires protein translation. Because changes
      in synaptic strength are regulated at the level of individual synapses, a
      mechanism is required for newly translated proteins to specifically and
      persistently modify only a subset of synapses. Evidence suggests this may be
      accomplished through local translation of proteins at or near synapses in
      response to plasticity-inducing patterns of activity. A number of proteins
      important for synaptic function are integral membrane proteins, which require a
      specialized group of organelles, proteins and enzymatic activities for proper
      synthesis. Dendrites appear to contain machinery necessary for the proper
      production of these proteins, and mRNAs for integral membrane proteins have been
      found localized to dendrites. Experiments are described that investigate the
      local translation of membrane proteins in the dendrites of cultured rat
      hippocampal neurons, using fluorescence recovery after photobleaching. Neurons
      were transfected with cDNAs encoding a fluorescently labeled transmembrane
      protein, TGN-38. Under conditions where the transport of this reporter construct
      was inhibited, the appearance of newly synthesized protein was observed via
      fluorescent microscopy. The dendritic translation of this protein required
      activation of glutamate receptors. The results demonstrate a functional capacity
      for activity-dependent synthesis of integral membrane proteins for distal
      dendrites in hippocampal neurons.

PMID- 15845075
TI  - Regulation of miRNA expression during neural cell specification.
AB  - MicroRNA (miRNA) are a newly recognized class of small, noncoding RNA molecules
      that participate in the developmental control of gene expression. We have studied
      the regulation of a set of highly expressed neural miRNA during mouse brain
      development. Temporal control is a characteristic of miRNA regulation in C.
      elegans and Drosophila, and is also prominent in the embryonic brain. We observed
      significant differences in the onset and magnitude of induction for individual
      miRNAs. Comparing expression in cultures of embryonic neurons and astrocytes we
      found marked lineage specificity for each of the miRNA in our study. Two of the
      most highly expressed miRNA in adult brain were preferentially expressed in
      neurons (mir-124, mir-128). In contrast, mir-23, a miRNA previously implicated in
      neural specification, was restricted to astrocytes. mir-26 and mir-29 were more
      strongly expressed in astrocytes than neurons, others were more evenly
      distributed (mir-9, mir-125). Lineage specificity was further explored using
      reporter constructs for two miRNA of particular interest (mir-125 and mir-128).
      miRNA-mediated suppression of both reporters was observed after transfection of
      the reporters into neurons but not astrocytes. miRNA were strongly induced during
      neural differentiation of embryonic stem cells, suggesting the validity of the
      stem cell model for studying miRNA regulation in neural development.

PMID- 15845076
TI  - Akt is altered in an animal model of Huntington's disease and in patients.
AB  - The insulin-like growth factor I (IGF-1)/Akt pathway plays a crucial role in
      Huntington's disease by phosphorylating the causative protein, polyQ-huntingtin,
      and abolishing its toxic properties [Humbert et al. (2002)Dev. Cell, 2, 831-837;
      Rangone et al. (2004)Eur. J. Neurosci., 19, 273-279]. Therefore, dysregulation of
      this pathway may be essential for disease progression. In the present report, we
      thus aimed to analyse the status of Akt in brain or in peripheral tissues in
      Huntington's disease. Using a genetic model of Huntington's disease in rat that
      reproduces neuronal dysfunction and death, we show a progressive alteration of
      Akt during neuronal dysfunction and prior neurodegeneration. By analysing a
      limited number of lymphoblasts and lymphocytes, we detected modifications of Akt
      in Huntington's disease patients confirming a dysregulation of Akt in the disease
      process. Finally, we demonstrate that during late stages of the disease, Akt is
      cleaved into an inactive form by caspase-3. These observations demonstrate a
      progressive but marked alteration of this pro-survival pathway in Huntington's
      disease, and further implicate it as a key transduction pathway regulating the
      toxicity of huntingtin.

PMID- 15845077
TI  - IGF-I neuroprotection in the immature brain after hypoxia-ischemia, involvement
      of Akt and GSK3beta?
AB  - Insulin-like growth factor I (IGF-I) is a neurotrophic factor that promotes
      neuronal growth, differentiation and survival. Neuroprotective effects of IGF-I
      have previously been shown in adult and juvenile rat models of brain injury. We
      wanted to investigate the neuroprotective effect of IGF-I after hypoxia-ischemia
      (HI) in 7-day-old neonatal rats and the mechanisms of IGF-I actions in vivo. We
      also wanted to study effects of HI and/or IGF-I on the serine/threonine kinases
      Akt and glycogen synthase kinase 3beta (GSK3beta) in the phophatidylinositol-3
      kinase (PI3K) pathway. Immediately after HI, phosphorylated Akt (pAkt) and
      phosphorylated GSK3beta (pGSK3beta) immunoreactivity was lost in the ipsilateral
      and reduced in the contralateral hemisphere. After 45 min, pAkt levels were
      restored to control values, whereas pGSK3beta remained low 4 h after HI.
      Administration of IGF-I (50 microg i.c.v.) after HI resulted in a 40% reduction
      in brain damage (loss of microtubule-associated protein) compared with vehicle
      treated animals. IGF-I treatment without HI was shown to increase pAkt whereas
      pGSK3beta decreased in the cytosol, but increased in the nuclear fraction. IGF-I
      treatment after HI increased pAkt in the cytosol and pGSK3beta in both the
      cytosol and the nuclear fraction in the ipsilateral hemisphere compared with
      vehicle-treated rats, concomitant with a reduced caspase-3- and caspase-9-like
      activity. In conclusion, IGF-I induces activation of Akt during recovery after HI
      which, in combination with inactivation of GSK3beta, may explain the attenuated
      activation of caspases and reduction of injury in the immature brain.

PMID- 15845078
TI  - Migration of cells from primary transplants of allo- and xenografted foetal
      striatal tissue in the adult rat brain.
AB  - Primary neural cells derived from human xenografts migrate extensively following
      transplantation into the adult rat CNS. However, it is unknown whether cells from
      allografts have the same capability to migrate within the adult rat brain.
      Moreover, it is unclear whether human-derived cells migrate to this extent as an
      inherent property of being in a xenograft environment, or whether it is due to
      the large size of the developed human brain compared with the adult rat brain. In
      order to address these issues we have designed an experimental paradigm to
      investigate the potential for cells derived from grafts of primary rat, mouse and
      human foetal striatal tissue to migrate following intrastriatal transplantation
      in an adult rat model of Huntington's disease (HD). Green fluorescent protein
      (GFP)-expressing rat and mouse donors and an antibody specific to human nuclear
      antigen enabled identification of graft-derived cells within the host brain, and
      double-labelling with GFP and neuronal nuclear antigen or immunostaining with
      human-specific tau identified graft-derived neurons. Twelve weeks post
      transplantation, cells had migrated throughout the host in all groups; however,
      human cells and neurons had migrated significantly more than rat or mouse cells.
      These results demonstrate that neural cells derived from allografts are capable
      of migrating in the adult rat CNS and that the extent of migration is most likely
      determined by the size of the mature donor adult brain. This has important
      implications for the use of allo- and xenogeneic tissue as a source for
      transplantation in treating diffuse neurodegenerative disorders such as HD.

PMID- 15845079
TI  - Regulation of corticosteroid receptors in the rat brain: the role of serotonin
      and stress.
AB  - It has been suggested that physiological resistance to repeated stress is
      associated with increased 5-hydroxytryptamine (5-HT) release in the dorsal
      hippocampus and that dysregulation of this neuroadaptation may be implicated in
      the psychopathology of depression. This study used 5,7-dihydroxytryptamine
      lesions to investigate the role of 5-HT projections to the hippocampus in
      physiological responses to repeated stress and putative changes in corticosteroid
      receptor immunoreactivity in the brain. Repeated exposure to elevated open
      platform stress (1 h/day) caused regionally selective changes in glucocorticoid
      and mineralocorticoid receptor immunoreactivity in the dorsal hippocampus that
      were not observed in ventral hippocampus, frontal cortex, hypothalamus or
      parietal cortex. Glucocorticoid receptor immunoreactivity in the dorsal
      hippocampus was decreased after 5 days but increased after 20 days of stress.
      Mineralocorticoid receptor immunoreactivity was increased after 5 or 10 days of
      stress. The increases in glucocorticoid and mineralocorticoid receptor
      immunoreactivity, evoked by repeated stress, were abolished by lesions of the
      principal 5-HT projections to the hippocampus. The lesions abolished the
      increased defecation observed in stressed animals, but had no effects on the
      plasma corticosterone response to the stressor or the habituation of this
      response observed following repeated stress. The experiments have revealed a
      dissociation in the regulation of corticosteroid receptor expression in the
      dorsal and ventral hippocampus by repeated stress and 5-HT. The data suggest that
      adaptation to inescapable stress is associated with regionally selective changes
      in corticosteroid receptor expression in dorsal hippocampus that are largely 5-HT
      dependent, although these changes do not mediate habituation of the pituitary
      adrenocortical response to the stressor.

PMID- 15845080
TI  - Postnatal ontogeny of hippocampal expression of the mineralocorticoid and
      glucocorticoid receptors in the common marmoset monkey.
AB  - The mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) are nuclear
      transcription factors that mediate many of the basal and stress functions and
      effects of the corticosteroid hormones, including those related to brain
      development. Despite this, relatively little is known about the postnatal
      ontogeny of MR and GR gene and protein expression in the central nervous system,
      and this is particularly true of the primates, including humans. Here we describe
      the postnatal ontogeny of central MR and GR gene and protein expression in the
      common marmoset monkey. By developing marmoset-specific riboprobes and using in
      situ hybridization, it was demonstrated that MR mRNA expression in the dentate
      gyrus and Ammon's horn was significantly greater in marmoset infants (aged 4-6
      weeks) than in neonates (1-2 days), juveniles (4-5 months) and adults (3-6
      years), with expression in the latter three ontogenetic stages being broadly
      similar. In the same subjects and ontogenetic stages, GR mRNA expression was
      developmentally consistent in the marmoset dentate gyrus and Ammon's horn, as
      well as in the paraventricular nucleus of the hypothalamus. Qualitative
      immunohistochemical comparison of infants and adults demonstrated that MR protein
      expression in the hippocampus was, as for mRNA, also greater in infants than
      adults, and that hippocampal GR protein was, as for mRNA, also similar in infants
      and adults. The increase in MR mRNA expression between the stages of neonate and
      infant co-occurred with a reduction in basal plasma ACTH and cortisol titres. The
      ontogenetic profiles of MR and GR gene expression in the marmoset monkey are
      therefore fundamentally different from those described for the rat and the mouse.
      This evidence for the postnatal ontogeny of central corticosteroid nuclear
      receptor expression in a primate is important for understanding both the
      developmental stage-specific significance of stress exposure and its potential
      long-term effects on health and disease.

PMID- 15845081
TI  - Estrogen enhances light-induced activation of dorsal raphe serotonergic neurons.
AB  - The serotonergic system has been implicated in the modulation of physiological
      processes including circadian rhythms, learning, memory, mood and food intake. In
      females, cessation of ovarian function produces deleterious changes in all of
      these processes and estrogen treatment often ameliorates these conditions.
      Estrogen may produce these effects by acting on the midbrain raphe, an estrogen
      sensitive region that receives direct projections from sensory systems. Here we
      examined the ability of estradiol to modulate neuronal responses of neurons
      within raphe nuclei to photic stimulation. Ovariectomized rats treated with
      estradiol or cholesterol were killed 1 h after the normal onset of light
      (Zeitgeber time 0) or after a 2-h phase advance (Zeitgeber time 22). In a second
      study, estradiol-treated ovariectomized rats under constant dark conditions were
      exposed to light 2 h before the subjective onset of circadian time [(CT)22] and
      killed 1 h later (CT23). The brains from all animals were processed for Fos
      and/or serotonin (5-HT) immunocytochemistry. Comparisons showed that the phase
      shift increased Fos immunoreactivity in all dorsal raphe nucleus (DRN) regions.
      Although estradiol did not alter the overall number of Fos-positive nuclei, it
      significantly increased the number of Fos/5-HT double-labelled cells in the
      medial and lateral DRN. In contrast, neither a phase shift nor estradiol altered
      the number of Fos-immunoreactive cells or the proportion of Fos-positive 5-HT
      cells in the median raphe nucleus. Results reveal that the DRN 5-HT system
      responds to changes in the light : dark cycle and that these responses are
      modulated by estrogen.

PMID- 15845082
TI  - The neuroprotective effect of progesterone after traumatic brain injury in male
      mice is independent of both the inflammatory response and growth factor
      expression.
AB  - Previous studies suggest that progesterone may possess neuroprotective properties
      after traumatic insult but, with the exception of reduced formation of cerebral
      oedema, limited experimental evidence has been presented to support this claim.
      In the present study we focused on the effect of progesterone treatment on
      structural and functional deficits in an experimental model of traumatic brain
      injury. Female mice exhibited significantly (P = 0.0445) reduced lesion volumes
      compared with males after aseptic cryogenic cerebral injury (ACI), suggesting
      that female sex steroids provide protection against this injury. In male mice,
      progesterone treatment after injury (three intraperitoneal doses of 8 mg/kg)
      reduced lesion volume (P = 0.0429) and improved performance in a spatial
      cognitive task (Morris water maze; P = 0.0014). However, progesterone had no
      demonstrable effect on the formation of oedema as measured using T2-weighted
      magnetic resonance imaging, nor did it affect brain water content. The pro
      inflammatory cytokines TNF-alpha and IL-1beta, and growth factors BDNF and G-CSF,
      were all strongly transcriptionally activated after ACI. However, progesterone
      administration did not affect expression of these genes. This study provides
      strong evidence that progesterone possesses neuroprotective properties in a mouse
      model of traumatic brain injury, but suggests that the steroid achieves this
      effect through mechanism(s) independent of the inflammatory response or growth
      factor up-regulation.

PMID- 15845083
TI  - Retinoic acid synthesis by a population of NG2-positive cells in the injured
      spinal cord.
AB  - Retinoic acid (RA) promotes growth and differentiation in many developing tissues
      but less is known about its influence on CNS regeneration. We investigated the
      possible involvement of RA in rat spinal cord injury (SCI) using the New York
      University (NYU) impactor to induce mild or moderate spinal cord contusion
      injury. Changes in RA at the lesion site were determined by measuring the
      activity of the enzymes for its synthesis, the retinaldehyde dehydrogenases
      (RALDHs). A marked increase in enzyme activity occurred by day 4 and peaked at
      days 8-14 following the injuries. RALDH2 was the only detectable RALDH present in
      the control or injured spinal cord. The cellular localization of RALDH2 was
      identified by immunostaining. In the noninjured spinal cord, RALDH2 was detected
      in oligodendroglia positive for the markers RIP and CNPase. Expression was also
      intense in the arachnoid membrane surrounding the spinal cord. After SCI the
      increase in RALDH2 was independent of the RIP- and CNPase-positive cells, which
      were severely depleted. Instead, RALDH2 was present in a cell type not previously
      identified as capable of synthesizing RA, that expressed NG2 and that was
      negative for markers of astrocytes, oligodendroglia, microglia, neurons, Schwann
      cells and immature lymphocytes. We postulate that the RALDH2- and NG2-positive
      cells migrate into the injured sites from the adjacent arachnoid membrane, where
      the RALDH2-positive cells proliferate substantially following SCI. These findings
      indicate that close correlations exist between RA synthesis and SCI and that RA
      may play a role in the secondary events that follow acute SCI.

PMID- 15845084
TI  - Spinal cord injury-induced lesional expression of the repulsive guidance molecule
      (RGM).
AB  - The repulsive guidance molecule (RGM) is involved in the formation of the central
      nervous system (CNS) during development by modulating guidance of growing axons.
      However, a role of RGM in CNS injury remains to be established. We studied the
      expression of RGM in the spinal cord of rats with spinal cord injury (SCI). After
      SCI, RGM+ cells accumulated in lesions and peri-lesional areas. During the first
      days after SCI, RGM expression was confined to neurons, ballooned neurite
      fibers/retraction bulbs, smooth muscle/endothelial cells, and to leucocytes
      infiltrating the lesion. Lesional RGM expression was frequently confined to
      hypertrophic beta-APP+ and RhoA+ neurites/retraction bulbs. With maturation of
      the lesion, we observed RGM expression by components of the developing scar
      tissue (cicatrix), such as fibroblastoid cells, reactive astrocytes and in
      addition a pronounced extracellular RGM deposition resembling neo-laminae.
      Frequent RGM+, RhoA+ coexpression by lesional retraction bulbs represent first
      preliminary evidence of RGM to exert growth inhibitory effects by the second
      messenger system RhoA. To date, RGM is one of the most potent axonal growth
      inhibitors identified and present in axonal growth impediments (i)
      oligodendrocytes; (ii) the plexus choroideus and (iii) components of the
      developing scar.

PMID- 15845086
TI  - Demonstration of long-range GABAergic connections distributed throughout the
      mouse neocortex.
AB  - Gamma-aminobutyric acid (GABA)ergic neurons in the neocortex have been mainly
      regarded as interneurons and thought to provide local interactions. Recently,
      however, glutamate decarboxylase (GAD) immunocytochemistry combined with
      retrograde labeling experiments revealed the existence of GABAergic projection
      neurons in the neocortex. We further studied the network of GABAergic projection
      neurons in the neocortex by using GAD67-green fluorescent protein (GFP) knock-in
      mice for retrograde labeling and a novel neocortical GABAergic neuron labeling
      method for axon tracing. Many GFP-positive neurons were retrogradely labeled
      after Fast Blue injection into the primary somatosensory, motor and visual
      cortices. These neurons were labeled not only around the injection site, but also
      at a long distance from the injection site. Of the retrogradely labeled GABAergic
      neurons remote from the injection sites, the vast majority (91%) exhibited
      somatostatin immunoreactivity, and were preferentially distributed in layer II,
      layer VI and in the white matter. In addition, most of GABAergic projection
      neurons were positive for neuropeptide Y (82%) and neuronal nitric oxide synthase
      (71%). We confirmed the long-range projections by tracing GFP-labeled GABAergic
      neurons with axon branches traveled rostro-caudally and medio-laterally. Axon
      branches could be traced up to 2 mm. Some (n = 2 of 4) were shown to cross the
      areal boundaries. The GABAergic projection neurons preferentially received
      neocortical inputs. From these results, we conclude that GABAergic projection
      neurons are distributed throughout the neocortex and are part of a
      corticocortical network.

PMID- 15845085
TI  - Two populations of glutamatergic axons in the rat dorsal raphe nucleus defined by
      the vesicular glutamate transporters 1 and 2.
AB  - Most glutamatergic neurons in the brain express one of two vesicular glutamate
      transporters, vGlut1 or vGlut2. Cortical glutamatergic neurons highly express
      vGlut1, whereas vGlut2 predominates in subcortical areas. In this study
      immunohistochemical detection of vGlut1 or vGlut2 was used in combination with
      tryptophan hydroxylase (TPH) to characterize glutamatergic innervation of the
      dorsal raphe nucleus (DRN) of the rat. Immunofluorescence labeling of both vGlut1
      and vGlut2 was punctate and homogenously distributed throughout the DRN. Puncta
      labeled for vGlut2 appeared more numerous then those labeled for vGlut1.
      Ultrastructural analysis revealed axon terminals containing vGlut1 and vGlut2
      formed asymmetric-type synapses 80% and 95% of the time, respectively.
      Postsynaptic targets of vGlut1- and vGlut2-containing axons differed in
      morphology. vGlut1-labeled axon terminals synapsed predominantly on small-caliber
      (distal) dendrites (42%, 46/110) or dendritic spines (46%, 50/110). In contrast,
      vGlut2-containing axons synapsed on larger caliber (proximal) dendritic shafts (>
      0.5 microm diameter; 48%, 78/161). A fraction of both vGlut1- or vGlut2-labeled
      axons synapsed onto TPH-containing dendrites (14% and 34%, respectively). These
      observations reveal that different populations of glutamate-containing axons
      innervate selective dendritic domains of serotonergic and non-serotonergic
      neurons, suggesting they play different functional roles in modulating excitation
      within the DRN.

PMID- 15845087
TI  - Vasopressin facilitates glycinergic and GABAergic synaptic transmission in
      developing hypoglossal motoneurons.
AB  - The hypoglossal nucleus of young rats contains vasopressin binding sites and
      vasopressin can directly excite hypoglossal motoneurons. In addition, indirect
      evidence suggests that vasopressin can enhance the synaptic input to motoneurons.
      We have characterized this latter effect by using brainstem slices and whole-cell
      recordings. We found that, in the presence of blockers of fast glutamatergic
      transmission, vasopressin strongly facilitated inhibitory synaptic activity. On
      average, vasopressin caused a six-fold increase in the frequency and a 1.5-fold
      increase in the amplitude of GABAergic postsynaptic currents. The effect of
      vasopressin on glycinergic postsynaptic currents was similar in magnitude.
      Vasopressin did not affect the frequency of GABAergic or glycinergic miniature
      postsynaptic currents, indicating that the peptide-induced facilitation of
      inhibitory transmission was mediated by receptors located on the somatodendritic
      region rather than on axon terminals of presynaptic neurons. The pharmacological
      profile of these receptors was determined by using d[Cha4]AVP and dVDAVP,
      selective agonists of V1b and V2 vasopressin receptors, respectively, and Phaa-D
      Tyr-(Et)-Phe-Gln-Pro-Arg-Arg-NH2, a selective antagonist of V1a vasopressin
      receptors. The two agonists had no effect on the frequency of inhibitory
      postsynaptic currents. By contrast, the antagonist suppressed the vasopressin
      induced facilitation of these currents, indicating that the receptors involved
      were exclusively of the V1a type. Thus, vasopressin exerts a dual action on
      hypoglossal motoneurons: a direct excitatory action and an indirect action
      mediated by GABAergic and glycinergic synapses. By virtue of this dual effect,
      vasopressin could alter the input-output properties of these motoneurons.
      Alternatively, it could play a role in generating or modulating specific motor
      patterns.

PMID- 15845088
TI  - Antagonist-induced supersensitivity of mGlu1 receptor signalling in cerebellar
      granule cells.
AB  - We investigated the effect of 24 h sustained treatment with the mGlu1 receptor
      antagonist CPCCOEt on mGlu1 receptor signalling in primary cultures of rat
      cerebellar granule cells. In the absence of ionotropic glutamate (iGlu) blockers,
      the maximal inositol phosphate (IP) response (E(max)) but not the potency of
      glutamate was significantly increased when cells were pre-exposed for 24 h with
      CPCCOEt. When the contribution of iGlu receptors to the glutamate-induced IP
      response was eliminated with the use of DNQX, the E(max) was again increased but
      also the concentration eliciting 50% of the maximal glutamate stimulus was
      significantly decreased. In the absence of iGlu receptor inhibitors, the E(max)
      of quisqualate, which likely mediates IP accumulation only via the mGlu1
      receptor, was significantly increased in CPCCOEt-pretreated cells. Also, less
      quisqualate was needed to reach the same IP effect. The potency of R193845, a
      selective mGlu1 receptor antagonist, was significantly decreased in antagonist
      pretreated cells. These findings demonstrate that 24 h sustained antagonist
      treatment can render mGlu1 receptors in neurons supersensitive to agonists, with
      a concomitant decrease in the effectiveness of antagonists.

PMID- 15845089
TI  - Presynaptic 'Ca2.3-containing' E-type Ca channels share dual roles during
      neurotransmitter release.
AB  - Ca2+ influx into excitable cells is a prerequisite for neurotransmitter release
      and regulated exocytosis. Within the group of ten cloned voltage-gated Ca2+
      channels, the Ca(v)2.3-containing E-type Ca2+ channels are involved in various
      physiological processes, such as neurotransmitter release and exocytosis together
      with other voltage-gated Ca2+ channels of the Ca(v)1, Ca(v)2 and Ca(v)3
      subfamily. However, E-type Ca2+ channels also exhibit several subunit-specific
      features, most of which still remain poorly understood. Ca(v)2.3-containing R
      type channels (here called 'E-type channels') are also located in presynaptic
      terminals and interact with some synaptic vesicle proteins, the so-called SNARE
      proteins, although lacking the classical synprint interaction site. E-type
      channels trigger exocytosis and are also involved in long-term potentiation.
      Recently, it was shown that the interaction of Ca(v)2.3 with the EF-hand motif
      containing protein EFHC1 is involved in the aetiology and pathogenesis of
      juvenile myoclonic epilepsy.

PMID- 15845090
TI  - Zinc ions are endogenous modulators of neurotransmitter-stimulated capacitative
      Ca2+ entry in both cultured and in situ mouse astrocytes.
AB  - Astrocytes express a variety of metabotropic receptors and their activation leads
      to a biphasic Ca2+ response due to Ca2+ release from intracellular stores and
      subsequent capacitative Ca2+ entry. We performed Ca2+ imaging with Fura-2 on
      cultured mouse astrocytes and showed that extracellular zinc reversibly blocks
      the capacitative Ca2+ entry following application of the metabotropic ligands
      ATP, glutamate and endothelin-1. Zinc blocked the plateau phase of the ligand
      triggered Ca2+ responses. When ligands were repetitively applied in the presence
      of zinc the calcium responses progressively decayed and even disappeared,
      indicating that capacitative Ca2+ entry is required to refill the stores. Zinc
      inhibited the capacitative Ca2+ entry with a K(i) of approximately 6 microM,
      which is well within the physiological concentration range of zinc found in the
      brain. Application of the reducing agent DTT prevented the blocking effect by
      zinc ions but not the inhibition elicited by the nonphysiological metal ions Gd3+
      and La3+, indicating that zinc has a distinct binding site. To monitor the
      capacitative Ca2+ entry in astrocytes in situ and to determine the effect of zinc
      on this pathway we utilized X-rhod-1 imaging in hippocampal slices of a
      transgenic mouse line with green fluorescent astrocytes. Zinc affected the
      repetitive metabotropic Ca2+ response in the following fashion: (i) after
      depleting stores in Ca(2+)-free solution, re-addition of Ca2+ led to an influx of
      Ca2+ via a zinc-sensitive Ca2+ entry route; (ii) with repetitive application of
      metabotropic ligands, Ca2+ responses became smaller and even disappeared in the
      presence of zinc. We conclude that zinc, which is co-released from glutamatergic
      synaptic vesicles upon neuronal activity, has a major impact on shaping the
      astrocytic calcium responses.

PMID- 15845091
TI  - Molecular and functional characterization of an I(h)-channel from lobster
      olfactory receptor neurons.
AB  - We isolated a cDNA named PAIH encoding a member of the I(h)-channel family
      expressed in olfactory receptor neurons (ORNs) of the spiny lobster Panulirus
      argus. Functional expression of recombinant PAIH in HEK293 cells generated a
      slowly activating, noninactivating inward current under whole-cell voltage-clamp
      to hyperpolarizing voltage steps, the amplitude and activation rate of which
      increase with increasing hyperpolarization. The channel is weakly selective for
      K+. Intracellular cAMP or cGMP shifts activation of the current to less negative
      potentials in a concentration-dependent manner. Finally, the channel is blocked
      by the I(h)-channel blocker ZD7288. An I(h)-channel sharing the properties of the
      recombinant channel occurs in cultured lobster ORNs. PAIH immunoreactivity
      localizes the protein to the transduction compartment of the ORNs in situ, and
      selectively applying the blocker to the transduction compartment reduces
      spontaneous activity in the ORN. Collectively, these results implicate for the
      first time a functional role for an I(h)-channel in olfactory signal
      transduction.

PMID- 15845092
TI  - Volume-sensitive chloride channels in mouse cortical neurons: characterization
      and role in volume regulation.
AB  - Because persistent swelling causes cell damage and often results in cell death,
      volume regulation is an important physiological function in both neuronal and non
      neuronal cells. Brain cell swelling has been observed not only in various
      pathological conditions but also during physiological synaptic transmissions.
      Volume-sensitive anion channels have been reported to play an important role in
      the regulatory volume decrease occurring after osmotic swelling in many cell
      types. In this study, using a two-photon laser scanning microscope and patch
      clamp techniques, we found that mouse cortical neurons in primary culture exhibit
      regulatory volume decrease after transient swelling and activation of Cl-
      currents during exposure to a hypotonic solution. The regulatory volume decrease
      was inhibited by Cl- channel blockers or K+ channel blockers. Swelling-activated
      Cl- currents exhibited outward rectification, time-dependent inactivation at
      large positive potentials, a low-field anion permeability sequence, an
      intermediate unitary conductance and sensitivity to known blockers of volume
      sensitive Cl- channels. Thus, it is concluded that the activity of the volume
      sensitive outwardly rectifying Cl- channel plays a role in the control of cell
      volume in cortical neurons.

PMID- 15845093
TI  - Neurons expressing relaxin 3/INSL 7 in the nucleus incertus respond to stress.
AB  - Relaxin 3/INSL 7 has recently been identified as a new member of the
      insulin/relaxin superfamily. Although it was reported to be dominantly expressed
      in the brain, its detailed distribution and function in the central nervous
      system are still obscure. In the present study we demonstrated that in the rat
      relaxin 3 was mainly expressed in neurons of the nucleus incertus (NI) of the
      median dorsal tegmental pons. Other relaxin 3-expressing neurons were scattered
      in the pontine raphe nucleus, the periaqueductal gray and dorsal area to the
      substantia nigra in the midbrain reticular formation. Relaxin 3-immunoreactive
      fibers projected particularly densely in the septum, hippocampus, lateral
      hypothalamus and intergeniculate leaflet of the thalamus. Ultrastructural
      examination revealed that relaxin 3 was localized in the dense-cored vesicles in
      the perikarya and was also observed in the synaptic terminals of axons. As almost
      all relaxin 3-containing neurons express corticotropin-releasing factor (CRF)
      type 1 receptor in the NI, we examined the response of relaxin 3 neurons to
      intracerebroventricular administration of CRF; 65% of relaxin 3 neurons expressed
      c-Fos 2 h after intracerebroventricular administration of 1 microg CRF. We then
      confirmed that c-Fos was induced in 60% of relaxin 3 neurons in the NI and the
      expression of relaxin 3 mRNA increased significantly in the NI after water
      restraint stress. Collectively, these results suggest that relaxin 3 produced in
      the NI is released from nerve endings and is involved in the regulation of the
      stress response.

PMID- 15845094
TI  - Regional cortical blood flow changes following sodium lactate infusion in
      Alzheimer's disease.
AB  - Bilateral temporoparietal hypoperfusion is a characteristic single photon
      emission computed tomography (SPECT) finding in Alzheimer's disease (AD). Lactate
      is a metabolic vasodilator and is known to provoke increased cerebral blood flow
      (CBF) in healthy adults. This work investigated whether lactate, which is present
      in high concentrations in AD cerebrospinal fluid, affects AD-specific perfusion
      abnormalities. Twenty mild-to-moderately demented AD probands participated in the
      self-controlled study. The regional CBF was examined utilizing (99m)Tc-HMPAO
      SPECT after sodium lactate infusion (0.5 M, 5 mL/kg body weight) and 0.9% NaCl
      infusion, one on each of two separate days. Despite the vasodilatator effects of
      sodium lactate, AD rCBF patterns did not show increase in temporo-parietal
      regions after its infusion. AD-specific bi-temporo-parietal reduction in CBF was
      accompanied by further hypoperfusion in the parieto-occipital areas after the
      sodium lactate infusion in seven patients, while no CBF changes were observed in
      the case of the remaining 13 probands. The pattern of the CBF abnormalities was
      not correlated with the apolipoprotein E genotype. The decreased vascular
      responsiveness to sodium lactate reflects disturbed vasoregulatory processes in
      AD and it is unlikely that lactate would have any relevance in the treatment of
      AD-related cerebral hypoperfusion, but could be used to improve the value of
      perfusion SPECT in the diagnosis of AD.

PMID- 15845095
TI  - Enhancement of learning behaviour by a potent nitric oxide-guanylate cyclase
      activator YC-1.
AB  - Memory is one of the most fundamental mental processes, and various approaches
      have been used to understand the mechanisms underlying this process. Nitric oxide
      (NO), cGMP and protein kinase G (PKG) are involved in the modulation of synaptic
      plasticity in various brain regions. YC-1, which is a benzylindazole derivative,
      greatly potentiated the response of soluble guanylate cyclase to NO (up to
      several hundreds fold). We have previously shown that YC-1 markedly enhances long
      term potentiation in hippocampal and amygdala slices via NO-cGMP-PKG-dependent
      pathway. We here further investigated whether YC-1 promotes learning behaviour in
      Morris water maze and avoidance tests. It was found that YC-1 shortened the
      escape latency in the task of water maze, increased and decreased the retention
      scores in passive and active avoidance task, respectively. Administration of YC-1
      30 min after foot-shock stimulation did not significantly affect retention scores
      in response to passive avoidance test. Administration of scopolamine, a
      muscarinic antagonist, markedly impaired the memory acquisition. Pretreatment of
      YC-1 inhibited the scopolamine-induced learning deficit. The enhancement of
      learning behaviour by YC-1 was antagonized by intracerebroventricular injection
      of NOS inhibitor L-NAME and PKG inhibitors of KT5823 and Rp-8-Br-PET-cGMPS,
      indicating that NO-cGMP-PKG pathway is also involved in the learning enhancement
      action of YC-1. YC-1 is thus a good drug candidate for the improvement of
      learning and memory.

PMID- 15845096
TI  - Involvement of NMDA and AMPA/KA receptors in the nucleus accumbens core in
      instrumental learning guided by reward-predictive cues.
AB  - The use of reward-predictive cues to guide behavior critically involves the
      nucleus accumbens. However, little is known regarding the role of ionotropic
      glutamate receptors in the core subregion of the nucleus accumbens (AcbC) in
      instrumental learning guided by reward-predictive cues. Here we examined the
      effects of an intra-AcbC blockade of NMDA and AMPA/KA receptors on the
      acquisition of an instrumental response in a reaction time (RT) task in rats. In
      this task, discriminative cues signaled in advance the upcoming reward magnitude
      (5 or 1 food pellet) associated with a lever release. During early acquisition
      (days 1-6) rats received daily bilateral injections of either the NMDA receptor
      antagonist AP5 (5.0 microg per side, n = 14), the AMPA/KA receptor antagonist
      CNQX (2.5 microg per side, n = 14) or vehicle (0.5 microL per side, n = 19). No
      treatment was given during late acquisition (days 7-12). The main result was that
      rats which received intra-AcbC injections of AP5 or CNQX during early acquisition
      exhibited a general RT increase of responses to high and low reward. However,
      treatment with AP5 and CNQX did not interfere with discriminative guidance of RTs
      by cue-associated reward magnitudes, i.e. during acquisition RTs of responses to
      expected high reward became significantly faster than RTs of responses to
      expected low reward. Our findings suggest that NMDA and AMPA/KA receptors in the
      AcbC play a critical role in invigorating responding during instrumental
      learning, but seem less important in guiding responding according to reward
      predictive cues.

PMID- 15845097
TI  - Contextual cues associated with nicotine administration increase arc mRNA
      expression in corticolimbic areas of the rat brain.
AB  - Conditioned responses to cues associated with the administration of drugs of
      misuse are an impediment to continued abstinence for drug-free addicted
      individuals. In order to study the neuroanatomical and cellular response of the
      brain to cues associated with nicotine administration, we conditioned Sprague
      Dawley rats to receive an ascending dose regimen of nicotine over 14 days in two
      distinct non-home cage environments and assessed expression of the early response
      gene arc in corticolimbic areas in response to the nicotine-associated context.
      All of the rats received the same dose regimen of nicotine. Three days after the
      last training day, the rats were exposed to the test environment. The rats that
      had previously received nicotine exhibited increased motor activity compared with
      the rats that had received saline in the test environment. After 45 min in the
      test environment, brains were taken for Northern blotting and in situ
      hybridization analysis, which revealed an increase in levels of activity
      regulated, dendritically localized mRNA for arc in a variety of brain regions
      (medial and lateral prefrontal cortices, cingulate cortex, primary sensory
      cortex, sensorimotor cortex, ventral striatum and amygdala). Plasma
      corticosterone levels were not different between the groups, suggesting that
      exposure to nicotine cues is insufficient to activate the hypothalamo-pituitary
      adrenal axis. Given that Arc plays a direct role in neuronal plasticity and
      memory consolidation, its induction by nicotine-associated cues in brain regions
      critical for cognitive and emotional processing suggests that rats may be
      learning that these cues are no longer necessarily predictive of nicotine
      administration. Further work will be needed in order to assess the role of arc
      expression in the extinction of conditioned responses to drug-paired cues.

PMID- 15845098
TI  - Down-regulation of amygdala preprotachykinin A mRNA but not 3H-SP receptor
      binding sites in subjects affected by mood disorders and schizophrenia.
AB  - Increasing evidence suggests that substance P (SP) neurokinin-1 (NK1) receptors
      are involved in stress and emotional responses, representing a potential target
      for the treatment of anxiety and depression in humans. Given the important role
      of the amygdaloid complex in the regulation of emotional behavior, we examined
      the mRNA levels of preprotachykinin A [PPT-A, a precursor of both SP and
      neurokinin A (NKA)] and 3H-SP binding sites in the amygdala of patients affected
      by bipolar disorder, major depression or schizophrenia as compared with matched
      control individuals. By means of in situ hybridization, a significant reduction
      of PPT-A mRNA expression levels was detected in the three diagnostic groups,
      mainly in the basal, lateral and accessory basal amygdaloid nuclei, but not in
      the temporal cortical area proximal to the amygdala. Receptor autoradiography
      performed on adjacent sections showed no change in 3H-SP binding sites as
      compared with controls. No significant correlation was found between levels of
      PPT-A mRNA expression or binding sites and subject age, gender, hemisphere side,
      cause of death or history of substance misuse (marijuana, alcohol,
      cocaine/amphetamine). An inverse relationship between PPT-A mRNA expression
      levels and lifetime antipsychotic treatment (Fluphenazine) in the schizophrenic
      and bipolar disorder groups was found. Post-mortem delay was also negatively
      correlated with NK1 binding sites. The results confirm an involvement of the
      tachykinins in psychiatric disorders, suggesting there is a generalized
      impairment of the SP system in the amygdala in mood disorders and schizophrenia
      rather than this being a disease-related phenomenon.

PMID- 15845099
TI  - Voluntary exercise rescues deficits in spatial memory and long-term potentiation
      in prenatal ethanol-exposed male rats.
AB  - Prenatal ethanol exposure can lead to long-lasting impairments in the ability to
      process spatial information in rats, as well as produce long-lasting deficits in
      the ability of animals to exhibit long-term potentiation, a biological model of
      learning and memory processing. Conversely, we have recently shown that both
      spatial memory and long-term potentiation can be enhanced in animals that are
      given access to a running wheel in their home cage. In the present study, Sprague
      Dawley rat dams were given one of three diets throughout gestation: (i) a liquid
      diet containing ethanol (35.5% ethanol-derived calories); (ii) a liquid diet,
      isocaloric to the ethanol diet, but with maltose-dextrin substituting for the
      ethanol derived calories and (iii) an ad libitum diet of standard rat chow. At
      weaning (28 days) animals were housed individually in either a standard rat cage,
      or a cage that contained a running wheel. Adult offspring were tested on a two
      trial version of the Morris water maze beginning at postnatal day 60, for five
      consecutive days. Following this, the capacity of the perforant path to dentate
      gyrus pathway to sustain long-term potentiation was examined in these animals
      using theta-patterned conditioning stimuli. Our results demonstrate that prenatal
      ethanol exposure can produce pronounced deficits in both spatial memory and long
      term potentiation, but that allowing animal's access to voluntary exercise can
      attenuate these deficits to the point that those exposed to ethanol prenatally
      can no longer be differentiated from control animals. These findings indicate
      that voluntary exercise may have therapeutic benefits for individuals that have
      undergone prenatal ethanol exposure.

PMID- 15845100
TI  - Right ear advantage for conspecific calls in adults and subadults, but not
      infants, California sea lions (Zalophus californianus): hemispheric
      specialization for communication?
AB  - This paper explores functional hemispheric asymmetries in the perception of
      auditory signals in a marine mammal species, the sea lion. Using a head-orienting
      task toward sounds we found a right ear--left hemisphere--advantage for
      conspecific calls in adult and subadult California sea lions (Zalophus
      californianus) that was absent in infants. Non-conspecific sounds did not elicit
      lateralized reactions in any age group. These findings show that maturational
      steps regarding communication in the brain of pinnipeds are similar to those
      described in primates. Such a result in a semi-aquatic species distant from
      primates on the phylogenetic tree speaks for a stability and an ancient emergence
      of the left hemispheric specialization for vocal communication. The origin of
      what seems to be a widespread brain feature might be searched in the temporal and
      spectral communicative sound's characteristics rather than in its semantic value.

PMID- 15845101
TI  - Autonomic arousal in an appetitive context in primates: a behavioural and neural
      analysis.
AB  - Central to many emotional responses is the accompanying peripheral somatic and
      autonomic arousal, feedback from which has been hypothesized to enhance emotional
      memory and to contribute to appraisal processes and decision making, and
      dysfunction of which may contribute to antisocial behaviour. Whilst peripheral
      arousal may accompany both positive and negative emotional contexts, its
      relationship with the former is poorly understood, as are the neural mechanisms
      underlying such a relationship. The purpose of the present study was to determine
      the autonomic correlates of anticipation, as well as consumption, of high
      incentive food, in the freely moving common marmoset and to investigate the
      contribution of the amygdala to such effects. Blood pressure (BP) and heart rate
      (HR) were measured remotely by a telemetric device implanted into the descending
      aorta and behavioural responses were monitored whilst marmosets viewed preferred
      or non-preferred foods and were then allowed access to eat those foods. A marked
      rise in blood pressure in unrestrained marmosets was observed in response both to
      the sight of highly preferred foods (anticipatory period) as well as during the
      actual consumption of those foods (consummatory period). Excitotoxic lesions of
      the amygdala abolished the autonomic arousal in the anticipatory period, but
      spared both the behavioural arousal in the anticipatory period and the autonomic
      arousal in the consummatory period. Together these data serve as an important
      step towards understanding the role of autonomic arousal in emotion and its
      neural underpinnings.

PMID- 15845102
TI  - Activity in human medial temporal lobe associated with encoding process in
      spatial working memory revealed by magnetoencephalography.
AB  - Animal studies have suggested that working memory may be affected after lesions
      in the medial temporal lobe, although this assumption has not been corroborated
      by neuropsychological studies in humans. However, very recently, several
      functional neuroimaging studies in humans have successfully observed activation
      of the medial temporal lobe during working memory tasks. The main aim of this
      study was to investigate the contribution of the medial temporal lobe to the
      encoding process in spatial working memory. To address this issue we registered
      the neuromagnetic brain patterns of eight adult volunteers while they performed a
      spatial working memory task and more perceptual task using identical stimuli.
      After a initial phase (between 200 and 400 ms) without differences in activation,
      the medial temporal lobe showed a sustained activity, more evident in the right
      hemisphere, lasting up to 800 ms during the encoding stage of the spatial working
      memory task, while the activation in the perceptual task terminated earlier
      (approximately 400 ms after stimulus onset). The finding of a continued
      activation of the medial temporal lobe strongly suggests the contribution of this
      brain region to encoding operations in working memory.

PMID- 15845103
TI  - Ratio and time requirements on operant schedules: effort-related effects of
      nucleus accumbens dopamine depletions.
AB  - Accumbens dopamine (DA) depletions produce deficits that are related to the ratio
      requirement of the operant schedule; however, it is also possible that time
      without reinforcement is a factor. The present study examined the effects of
      accumbens DA depletions in rats using variable interval (VI) schedules with
      additional fixed ratio (FR) requirements. Four VI schedules were used (VI 60/FR
      1, VI 120/FR 1, VI 60/FR 10, VI 120/FR 10). Attachment of the additional work
      requirement increased response rates under control conditions. After surgery,
      there was no interaction between interval level (i.e. 60 vs. 120 s) and DA
      depletion, but there was a significant interaction between ratio requirement
      (i.e. 1 vs. 10) and DA depletion within the first week after surgery. DA
      depletions substantially impaired performance on the schedules with added FR 10
      requirements, an effect that was largely dependent upon a reduction in fast
      responses (i.e. inter-response times less than 1.0 s). There was little effect of
      DA depletion on overall responding on VI 60/FR 1 and VI 120/FR 1 schedules. DA
      depletions also increased the tendency to take long pauses in responding (i.e. >
      20.0 s), and this effect was evident across all schedules tested. Thus, accumbens
      DA depletions interact with work requirements and blunt the rate-enhancing
      effects of moderate size ratios, and also enhance the tendency to pause.
      Attachment of ratio requirements to interval schedules is a work-related response
      cost that provides a challenge to the organism, and DA in nucleus accumbens
      appears to be necessary for adapting to this challenge.

PMID- 15845104
TI  - Zebrafish embryos are susceptible to the dopaminergic neurotoxin MPTP.
AB  - The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces
      selective loss of dopaminergic neurons in the mammalian midbrain, eliciting
      symptoms characteristic of Parkinson's disease. By exploiting the advantages of
      zebrafish embryos, we report here that dopaminergic neurons in this species are
      specifically perturbed when exposed to MPTP. In contrast to mammals, the
      zebrafish does not possess a midbrain dopaminergic system. Instead, the main
      population of neurons expressing the dopamine transporter is located in the
      posterior tuberculum of the diencephalon. Exposure of embryos to MPTP led to a
      pronounced reduction in the number of dopaminergic cells in the diencephalon.
      This effect can be reversed by deprenyl, a specific inhibitor of monoamine
      oxidase B that catalyses the conversion of MPTP to its active metabolite, MPP+.
      Similarly, direct treatment of embryos with MPP+ abolished the diencephalic
      dopaminergic neurons. These larvae also demonstrated behavioural defects in
      swimming responses. Thus, dopaminergic neurons in the posterior tuberculum of the
      zebrafish may be homologous to the midbrain dopaminergic system of mammals. In
      addition, the mechanism behind the loss of dopaminergic neurons following
      pharmacological perturbation may be conserved among vertebrates and suggest that
      the zebrafish can be used as a convenient and economical system to study the
      pathogenesis of Parkinson's disease and for testing potential therapeutic
      strategies.

PMID- 15845106
TI  - Abstracts presented at the Annual Scientific Meeting of the Australian Society
      for Geriatric Medicine, 2004.

PMID- 15845105
TI  - Adult gaze influences infant attention and object processing: implications for
      cognitive neuroscience.
AB  - Infants follow others' gaze toward external objects from early in ontogeny, but
      whether they use others' gaze in processing information about objects remains
      unknown. In Experiment 1, 4-month-old infants viewed a video presentation of an
      adult gazing toward one of two objects. When presented with the same objects
      alone a second time, infants looked reliably less at the object to which the
      adult had directly gazed (cued object). This suggests that the uncued object was
      perceived as more novel than the object previously cued by the adult's gaze. In
      Experiment 2, adult gaze was not directed towards any object. In this control
      experiment, infants looked at both objects equally in the test phase. These
      findings show that adult eye gaze biases infant visual attention and information
      processing. Implications of the paradigm for cognitive neuroscience are presented
      and the results are discussed in terms of neural structures and change over
      ontogeny.

PMID- 15845107
TI  - Medical work hours: time for a Maggie's Law for doctoring?

PMID- 15845108
TI  - Burnout in physicians: a case for peer-support.
AB  - BACKGROUND: It is well documented that doctors experience a high level of stress
      in their profession, and that this can lead to physical, psychological, and
      emotional harm, in particular, burnout. Overseas (especially in the UK and USA),
      research investigating the levels of stress, burnout, and associated psychiatric
      morbidity in health professionals, across many specialties, has been carried out
      with a view to prevention of these adverse outcomes. AIMS: To assess the level of
      burnout in a sample of New Zealand physicians, the associated work and personal
      characteristics, and the need for development of a support peer supervision or
      support system. METHODS: Questionnaires that measured a number of work and
      personal characteristics, including the Maslach Burnout Inventory, the General
      Health Questionnaire, and additional questions regarding mistakes, and need for
      support, were sent to 83 physicians in the Waikato and Bay of Plenty areas.
      Analysis involved descriptive statistics, with t-tests for comparison with other
      studies, Pearson Product-Moment correlations between variables and analysis of
      variance where appropriate. RESULTS: Of the 50 respondents, 28% experienced high
      levels of two or three aspects of burnout (emotional exhaustion,
      depersonalization, low personal accomplishment). Emotional exhaustion correlated
      with a greater need for support. Most respondents favoured a one-to-one support
      system. CONCLUSION: This study highlights the presence of significant workplace
      difficulties for physicians and the need to develop a preventative support system
      for the protection of physicians and the patients in their care.

PMID- 15845109
TI  - Failure of current public educational campaigns to impact on the initial response
      of patients with possible heart attack.
AB  - AIMS: The National Heart Foundation of Australia recognizes that the risk of
      lethal arrhythmias is greater very early after the onset of myocardial infarction
      and that the more promptly flow can be restored in the infarct-related artery the
      greater will be the benefits for survival and preservation of heart function. The
      Heart Foundation has therefore conducted several public media campaigns to
      encourage patients to seek help more promptly and evaluated their impact.
      METHODS: Since 1996, we have conducted four surveys of delays preceding admission
      of patients to coronary care units throughout Australia to assess the impact of
      the Heart Foundation's media campaigns. Data were collected on 1665 patients who
      presented to 73 hospitals; information on patient delay was available for 1178 of
      them. RESULTS: There were no significant differences in patient delay (median 1.5
      2.0 h) in the four surveys from 1996 to 2002, nor when patients were categorized
      by age, sex, presenting diagnosis or history of previous myocardial infarction or
      coronary revascularization by percutaneous or surgical techniques. CONCLUSION:
      New approaches are needed to reduce patient-related delay after the onset of
      symptoms suggesting possible myocardial infarction.

PMID- 15845110
TI  - Clinical audit of the use of fresh-frozen plasma and platelets in a tertiary
      teaching hospital and the impact of a new transfusion request form.
AB  - AIM: To carry out an audit of the appropriateness of fresh-frozen plasma (FFP)
      and platelets (Plt) transfusion with reference to the Australian National Health
      and Medical Research Council/Australian Society of Blood Transfusion Clinical
      Practice Guidelines, and to assess the impact of a self-educating transfusion
      request form. METHODS: A prospective review of the clinical indications and
      laboratory data in all transfusion episodes of FFP and Plt occurring in a
      tertiary teaching hospital in South Australia in two 2-month periods of the years
      2002 and 2003. RESULTS: Reversal of warfarin has emerged as the major indication
      to transfuse FFP (34%). More than 72% FFP and 88% Plt were prescribed in an
      appropriate manner, and the majority were monitored adequately. The transfusion
      request form further improved the appropriate uses and was met with a
      satisfactory compliance. Further grounds for improvement are in FFP usage by the
      haematology unit and in cardiac bypass surgery, and Plt by surgical units.
      CONCLUSION: Clinical transfusion audit helps to identify current pattern of usage
      and areas of improvement. A self-educating transfusion specific request form is
      also beneficial.

PMID- 15845111
TI  - Homocysteine, renal disease and cardiovascular disease in a remote Australian
      Aboriginal community.
AB  - BACKGROUND: Rates of renal and cardiovascular disease are high among Aboriginal
      Australians living in remote communities. Nutritional problems, in particular low
      folate levels, are also common. This suggests that increased homocysteine
      concentrations might be widespread, and a possible contributor to the high rates
      of cardiovascular disease. AIMS: To examine homocysteine concentrations, and
      their relationships to folate levels, and to markers of renal disease and
      cardiovascular disease in a remote Aboriginal Australian community METHODS: As
      part of a cross-sectional survey among adults in one community, homocysteine
      concentrations, concentrations of the crucial determinants (red blood cell (RBC)
      folate, vitamin B(12) and the C677T methylene tetrahydrofolate reductase
      polymorphism) and cardiovascular risk factors were examined. RESULTS: Among 221
      people, geometric mean homocysteine concentration was 11.8 micromol/L (range:
      11.1-12.5 micromol/L), with 57/221 (26%) values > or =15.0 micromol/L. Higher
      concentrations were associated with older age, male gender, lower RBC folate and
      lower vitamin B(12) concentrations and homozygosity for C677T. Homocysteine
      concentrations were not related to the presence of albuminuria, other than over
      the overt albuminuria range. Homocysteine concentrations were inversely
      correlated with calculated glomerular filtration rate (GFR). Carotid intima-media
      thickness, however, was not related to homocysteine concentration. In
      multivariate analyses, age, male gender, lower RBC folate concentrations, lower
      vitamin B(12) concentrations, lower calculated GFR and the C677T polymorphism
      were all associated with homocysteine concentrations. CONCLUSIONS: Homocysteine
      concentrations were consistent with previous limited reports in Aboriginal
      communities. Although superficially they are similar to reports from non
      Aboriginal settings, the younger age of this cohort and the association of
      homocysteine concentrations with age suggest that age-specific concentrations are
      higher among Aboriginal Australians. In addition to dietary determinants, the
      high prevalence of apparently reduced renal function renal disease appears to be
      an important determinant of homocysteine concentrations in remote Aboriginal
      communities. The role of homocysteine concentrations as a potential mediator of
      the high rates of cardiovascular disease remains to be determined.

PMID- 15845112
TI  - How far does a doctor's 'duty of care' go?
AB  - It is a long-standing tradition in medicine that doctors have an ethical duty to
      care for all patients who fall within the scope of their skill base. This duty
      reflects the value system of many doctors and the type of typical dedication to
      their craft that has long been expected and given. The modern doctor, however,
      may have other additional roles -- such as those of parent, researcher, business
      person and many others. What about the duties that accompany these other
      activities and what if these duties come into conflict with the duty to care for
      patients? How does a doctor decide how far the duty to care for patients extends?
      This article explores this question of duty and discusses how the notion of the
      traditional doctor's duty to care may need to be amended in light of the kinds of
      lives that doctors now lead.

PMID- 15845113
TI  - Readmission patterns in patients with chronic obstructive pulmonary disease,
      chronic heart failure and diabetes mellitus: an administrative dataset analysis.
AB  - Comprehensive disease management programmes for chronic disease aim to improve
      patient outcomes and reduce health-care utilization. Readmission rates are often
      used as an outcome measure of effectiveness. This study aimed to document
      readmission rates, and risk for early and late readmission, for patients
      discharged from the Royal Melbourne Hospital with a disease diagnosis of chronic
      heart failure (CHF), chronic obstructive pulmonary disease (COPD) or diabetes
      mellitus compared to those with other general medical conditions. Eighty five
      (8.6%) of patients were readmitted within 28 days and 183 (20.8%) were readmitted
      between 29 and 180 days. No risk factors for early readmission were identified.
      Patients with a primary disease diagnosis of CHF and COPD are at increased risk
      of late readmissions (29-180 days).

PMID- 15845114
TI  - Intra-arterial thrombolysis in acute ischaemic stroke.
AB  - Several thrombolytic agents for the treatment of acute ischaemic stroke have been
      examined; however, to date, only the i.v. administration of recombinant tissue
      plasminogen activator is licensed in Australia. Although no trials directly
      comparing intra-arterial and i.v. delivery of thrombolytics exist, intra-arterial
      thrombolysis has several potential advantages, including angiographic assessment
      of the thrombus and the site of occlusion and collateral circulation, improved
      recanalization, and delivery of higher local concentrations of thrombolytic
      agents and extending the therapeutic time window for treatment. We conducted a
      retrospective audit of our experience with the use of intra-arterial urokinase to
      treat acute ischaemic stroke at an Australian tertiary-care hospital between June
      1993 and June 2003. We examined time from stroke onset to assessment,
      computerized tomography scan, cerebral angiography and thrombolysis, anatomical
      classification of intra-arterial thrombus, rates of symptomatic intracerebral
      haemorrhage, and clinical outcome at 3 months. We believe that in carefully
      selected individuals in appropriate centres of expertise, intra-arterial
      thrombolytic therapy holds great promise.

PMID- 15845115
TI  - Cardiac metastases: ante-mortem diagnosis with cardiac magnetic resonance
      imaging.

PMID- 15845116
TI  - Determining the professional attributes of a hospitalist: experience in one
      Australian metropolitan hospital.
AB  - Data were prospectively recorded on 1294 consecutive patients admitted to a
      General Medical Unit at the Gold Coast Hospital to review the caseload and pre
      requisite professional skills of a general physician working as a full-time
      hospitalist. Based on this review, the general physician hospitalist must possess
      expertise in the management of common medical conditions and comorbidities,
      uncommon medical conditions, elderly patients, the seriously ill, the terminally
      ill, psychiatric patients, surgical patients and patients with dermatologic,
      ophthalmic and gynaecological problems. The hospitalist must also be proficient
      in medical education and organization governance. The demonstration of such
      skills ensures the 'hospitalist' model is efficient and effective for hospital
      based care.

PMID- 15845117
TI  - Diabetes in the young: not always as it seems.

PMID- 15845118
TI  - Alpha-1 antitrypsin deficiency diagnosed in an 86-year-old-man.

PMID- 15845119
TI  - Measurement of serum vascular endothelial growth factor in breast cancer
      patients.

PMID- 15845120
TI  - Ethics committee approval of multicentre studies.

PMID- 15845123
TI  - Doctors not well served by their illicit drug policy.

PMID- 15845125
TI  - Where have all the clinical trials gone?

PMID- 15845126
TI  - Practitioner review: early adversity and developmental disorders.
AB  - BACKGROUND: Knowledge of genetic influences, on developmental disorders such as
      autism spectrum, attention deficit/hyperactivity disorder and learning
      disabilities, has increased the opportunities for understanding the influences of
      the early environment. METHODS: This paper provides a selective, narrative review
      for clinicians of the effects of factors such as exposure to toxins and stresses
      in utero and in postnatal life; brain injuries and perinatal compromise; neglect,
      malnutrition and selective food deficiencies. It also considers what is known
      about the mechanisms through which early adversities operate. RESULTS: Gaps in
      the research are identified and suggestions made about clinical investigations.
      Several types of environmental adversity have associations with later disorders
      that suggest a causal role. The effects are often on a broad range of
      psychological processes, and are not always quickly reversible. Several
      adversities often coexist, calling for skilled judgement about priorities in
      treatment. CONCLUSIONS: Individuals vary considerably in their exposure to
      adversity and their vulnerability to its effects, and genetic inheritance can
      influence both.

PMID- 15845127
TI  - Participation in power sports and antisocial involvement in preadolescent and
      adolescent boys.
AB  - BACKGROUND: A limited number of mostly cross-sectional studies have examined the
      possible effects of power sports on aggressive and antisocial involvement in
      children and youth. The majority of these studies have serious methodological
      limitations, and results are partly contradictory. Longitudinal studies with
      representative, reasonably large samples and adequate dependent variables are
      lacking. METHODS: The relationship between participation in power or fight and
      strength sports (boxing, wrestling, weightlifting, and oriental martial arts) and
      violent and antisocial behaviour was examined in a sample of 477 boys, aged 11 to
      13 years at Time 1, over a two-year period. Making use of information about
      different participation patterns over time, the longitudinal design provided an
      opportunity to examine specified hypotheses about possible causal effects of
      power sports. RESULTS: The total pattern of results strongly suggests that
      participation in power sports actually leads to an increase or enhancement of
      antisocial involvement in the form of elevated levels of violent as well as non
      violent antisocial behaviour outside sports. In addition, there were no
      indications of selection effects; the presence of such effects would imply that
      boys who started with power sports were characterised by already elevated levels
      of antisocial involvement. CONCLUSIONS: The results provide strong support for
      the 'enhancement hypothesis'. The negative effects in boys seemed to stem from
      both the practice of power sports itself and from repeated contact with 'macho'
      attitudes, norms, and ideals. The negative effects of participation in power
      sports represent a societal problem of considerable dimensions which has been
      largely neglected up to now.

PMID- 15845128
TI  - Towards a family process model of maternal and paternal depressive symptoms:
      exploring multiple relations with child and family functioning.
AB  - BACKGROUND: Research has focused on maternal dysphoria and child adjustment.
      However, family process models indicate gaps in the study of paternal dysphoria,
      broader family functioning, and diverse child outcomes. METHOD: A community
      sample of 235 mothers and fathers of kindergarten children completed measures of
      depressive symptoms, family functioning and child adjustment. Teachers also
      provided measures of child adjustment. RESULTS: Supportive of pervasive effects
      even in a community sample, increased parental depressive symptomatology was
      related to increased marital conflict, insecure marital attachment, less parental
      warmth, more psychological control in parenting, and multiple child problems.
      Child gender moderated child outcomes differently for paternal and maternal
      dysphoria. Marital relations, but not parenting, mediated child outcomes.
      CONCLUSIONS: Marital problems may be especially reactive to parental depressive
      symptomatology, so that mediational processes affecting child functioning become
      evident even in family contexts of relatively low risk.

PMID- 15845129
TI  - Mediating links between maternal depression and offspring psychopathology: the
      importance of independent data.
AB  - BACKGROUND: Research examining intergenerational transmission of psychopathology
      is often limited by reliance on the same individuals for information on multiple
      constructs of interest. To counteract this limitation, data from a prospective,
      longitudinal study of at-risk youth were analyzed to test the hypothesis that
      parenting and family environmental factors mediate the association between
      maternal depressive symptoms and offspring psychopathology in late adolescence.
      METHOD: Data were taken from 184 families of the Minnesota Longitudinal Study of
      Parents and Children. Measures included the CES-D and Beck depression
      inventories, home environment ratings and a family conflict scale, and CBCL
      behavior problem checklist and K-SADS psychiatric symptom scores. Regression
      analyses were conducted to test for mediation of maternal depression effects by
      family environmental factors. RESULTS: Analyses using a single informant and time
      point showed evidence for substantial mediation; however, in analyses spanning
      independent informants and multiple time points mediating effects were markedly
      reduced. Sex differences were found, in that parenting and family environmental
      factors related to psychopathology for males, whereas maternal depression was
      more directly related to psychopathology for females. CONCLUSIONS: Results
      emphasize the importance of independent data for testing mediational claims, and
      support claims that the processes involved in the intergenerational transmission
      of psychopathology are different for male and female youth.

PMID- 15845130
TI  - Outcome at 7 years of children diagnosed with autism at age 2: predictive
      validity of assessments conducted at 2 and 3 years of age and pattern of symptom
      change over time.
AB  - OBJECTIVE: To examine the predictive validity of symptom severity, cognitive and
      language measures taken at ages 2 and 3 years to outcome at age 7 in a sample of
      children diagnosed with autism at age 2. METHOD: Twenty-six children diagnosed
      with autism at age 2 were re-assessed at ages 3 and 7 years. At each age symptom
      severity, cognitive and language assessments were completed. RESULTS: The pattern
      of autistic symptom severity varied over time by domain. Across time, children
      moved across diagnostic boundaries both in terms of clinical diagnosis and in
      terms of instrument diagnosis on the Autism Diagnostic Interview-Revised (ADI-R).
      On all measures group variability in scores increased with age. Although non
      verbal IQ (NVIQ) for the group as a whole was stable across the 3 assessments,
      this masked considerable individual instability. Standard assessments at age 2
      did not predict outcome at age 7 even within the same domain of functioning. In
      contrast, standard assessments at age 3 did predict outcome. However, a measure
      of rate of non-verbal communicative acts taken from an interactive play-based
      assessment at age 2 was significantly associated with language, communication and
      social outcomes at age 7. CONCLUSIONS: The trajectory of autism symptoms over
      time differed in different domains, suggesting that they may be, at least in
      part, separable. Variability in language, NVIQ and symptom severity increased
      over time. Caution is required when interpreting the findings from assessments of
      children with autism at age 2 years. At this age measures of rate of non-verbal
      communication might be more informative than scores on standard psychometric
      tests. Predictive validity of assessments at age 3 years was greater.

PMID- 15845131
TI  - Aversion, awareness, and attraction: investigating claims of hyperacusis in the
      Williams syndrome phenotype.
AB  - BACKGROUND: Williams syndrome (WS), a neurodevelopmental disorder, is
      characterized by pervasive cognitive deficits alongside a relative sparing of
      auditory perception and cognition. A frequent characteristic of the phenotype is
      adverse reactions to, and/or fascination with, certain sounds. Previously
      published reports indicate that people with WS experience hyperacusis, yet
      careful examination reveals that the term 'hyperacusis' has been used
      indiscriminately in the literature to describe quite different auditory
      abnormalities. METHOD: In an effort to clarify and document the incidence of
      auditory abnormalities in and among people with WS we collected data from parents
      of people with WS (n = 118) and comparison groups of people with Down syndrome,
      autism, and normal controls. RESULTS: Our findings revealed four
      phenomenologically separate auditory abnormalities, all of which were
      significantly more prevalent in WS than the three comparison groups. Among people
      with WS, we found relatively few reports of true hyperacusis (lowered threshold
      for soft sounds) or auditory fascinations/fixations, whereas 80% reported
      fearfulness to idiosyncratically particular sounds, and 91% reported lowered
      uncomfortable loudness levels, or 'odynacusis.' CONCLUSIONS: Our results confirm
      anecdotal reports of an unusual auditory phenotype in WS, and provide an
      important foundation for understanding the nature of auditory experience and
      pathology in WS. We conclude by reviewing the ways in which the present findings
      extend and complement recent neuroanatomical and neurophysiological findings on
      auditory function in people with WS.

PMID- 15845132
TI  - Literacy difficulties and psychiatric disorders: evidence for comorbidity.
AB  - BACKGROUND: Literacy difficulties show high levels of comorbidity with both
      disruptive and emotional disorders, but questions remain over the nature and
      specificity of these links. METHOD: Relationships between specific literacy
      difficulties and psychiatric disorder were investigated in a large-scale national
      sample of children aged 9 to 15 years. RESULTS: Specific literacy difficulties
      were more common in children from lower socio-economic backgrounds, and were
      significantly associated with increased risks of Attention-Deficit Hyperactivity
      Disorder (especially inattentive symptomatology), Conduct Disorder and anxiety
      disorders in both girls and boys, and with self-reports of depressed mood in
      boys. Associations between literacy difficulties and diagnoses of both Attention
      Deficit Hyperactivity Disorder (ADHD) and Conduct Disorder (CD) were mediated by
      inattentiveness, as were links with low mood. Links between specific literacy
      difficulties and anxiety were of a different nature, suggestive of a direct
      impact of literacy problems on risk for anxiety disorders. CONCLUSIONS: Literacy
      difficulties are significantly associated with externalizing disorders via
      inattention, but may constitute a more immediate risk factor for naturally
      anxious children to develop clinically significant levels of anxiety.

PMID- 15845133
TI  - Central coherence in typically developing preschoolers: does it cohere and does
      it relate to mindreading and executive control?
AB  - BACKGROUND: Frith and Happe (1994) describe central coherence (CC) as the normal
      tendency to integrate individual elements into a coherent whole, a cognitive
      style which varies in the general population. Individuals with autism are at the
      extreme (weak) end of the continuum of coherence. There has been debate over
      whether CC is independent from other psychological functions such as theory of
      mind and executive control. METHODS: We examined the validity of the CC construct
      in 76 typically developing 4- and 5-year-old children using four visuospatial
      coherence tasks. We also investigated the extent to which individual differences
      in performance on CC measures were associated with individual differences on
      measures of mindreading and executive functioning (EF). RESULTS: Unexpectedly,
      the CC variables were not highly intercorrelated and did not form a single
      coherence factor. Instead, the results revealed a two-factor structure, one of
      which corresponded to visuospatial constructional ability. Correlations between
      the emerging factors of coherence and mindreading ability were weak, even when
      developmental differences in age and verbal and nonverbal ability were taken into
      account. In contrast, visuospatial constructional ability was reliably related to
      measures of EF, whilst correlations between EF and the second CC factor were very
      weak. CONCLUSIONS: CC in typically developing preschoolers is not a unitary
      construct. Whilst there is little relationship between CC and mindreading
      abilities in these young children, executive control appears to be associated
      with one aspect of coherence: visuospatial construction.

PMID- 15845134
TI  - A new measure of children's optimism and pessimism: the youth life orientation
      test.
AB  - BACKGROUND: Optimism and pessimism are positive and negative expectations linked
      with well-being in adults. Research on the importance of optimism and pessimism
      in children is limited by the lack of a developmentally appropriate measure of
      children's expectations. METHOD: Based upon the Life Orientation Test-Revised
      (Scheier, Carver, & Bridges, 1994), the Youth Life Orientation Test (YLOT) is a
      sixteen-item self-report measure of children's optimism and pessimism. RESULTS:
      Reliability and validity of the YLOT was found with 204 3rd-6th graders. Optimism
      also predicted fewer child-reported depressive symptoms and parent-reported
      behavior problems assessed three months later. Pessimism predicted more child
      reported anxiety symptoms and parent-reported social and academic deficits.

PMID- 15845137
TI  - Assessing post-traumatic stress disorder in South African adolescents: using the
      child and adolescent trauma survey (CATS) as a screening tool.
AB  - BACKGROUND: Several studies have demonstrated that South African children and
      adolescents are exposed to high levels of violent trauma with a significant
      proportion developing PTSD, however, limited resources make it difficult to
      accurately identify traumatized children. METHODS: A clinical interview (K-SADS
      PL, selected modules) and self-report scale (CATS) were compared to determine if
      these different methods of assessment elicit similar information with regards to
      trauma exposure and post-traumatic stress disorder (PTSD) in adolescents. Youth
      (n = 58) from 2 schools in Cape Town, South Africa participated. RESULTS: 91% of
      youth reported having been exposed to a traumatic event on self-report (CATS) and
      38% reported symptoms severe enough to be classified as PTSD. On interview (K
      SADS-PL), 86% reported exposure to a traumatic event and 19% were found to have
      PTSD. While there were significant differences in the rates of trauma exposure
      and PTSD on the K-SADS and CATS, a cut-off value of 15 on the CATS maximized both
      the number of true positives and true negatives with PTSD. The CATS also
      differentiated well between adolescents meeting DSM-IV PTSD symptom criteria from
      adolescents not meeting criteria. CONCLUSIONS: Our results indicate that trauma
      exposure and PTSD are prevalent in South African youth and if appropriate cut
      offs are used, self-report scales may be useful screening tools for PTSD.

PMID- 15845138
TI  - QT interval prolongation related to psychoactive drug treatment: a comparison of
      monotherapy versus polytherapy.
AB  - BACKGROUND: Several antipsychotic agents are known to prolong the QT interval in
      a dose dependent manner. Corrected QT interval (QTc) exceeding a threshold value
      of 450 ms may be associated with an increased risk of life threatening
      arrhythmias. Antipsychotic agents are often given in combination with other
      psychotropic drugs, such as antidepressants, that may also contribute to QT
      prolongation. This observational study compares the effects observed on QT
      interval between antipsychotic monotherapy and psychoactive polytherapy, which
      included an additional antidepressant or lithium treatment. METHOD: We examined
      two groups of hospitalized women with Schizophrenia, Bipolar Disorder and
      Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of
      nineteen hospitalized women treated with antipsychotic monotherapy (either
      haloperidol, olanzapine, risperidone or clozapine) and Group 2 was composed of
      nineteen hospitalized women treated with an antipsychotic (either haloperidol,
      olanzapine, risperidone or quetiapine) with an additional antidepressant
      (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine,
      venlafaxine or clomipramine) or lithium. An Electrocardiogram (ECG) was carried
      out before the beginning of the treatment for both groups and at a second time
      after four days of therapy at full dosage, when blood was also drawn for
      determination of serum levels of the antipsychotic.Statistical analysis included
      repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. RESULTS: Mean
      QTc intervals significantly increased in Group 2 (24 +/- 21 ms) however this was
      not the case in Group 1 (-1 +/- 30 ms) (Repeated measures ANOVA p < 0,01).
      Furthermore we found a significant difference in the number of patients who
      exceeded the threshold of borderline QTc interval value (450 ms) between the two
      groups, with seven patients in Group 2 (38%) compared to one patient in Group 1
      (7%) (Fisher Exact Text, p < 0,05). CONCLUSIONS: No significant prolongation of
      the QT interval was found following monotherapy with an antipsychotic agent,
      while combination of these drugs with antidepressants caused a significant QT
      prolongation. Careful monitoring of the QT interval is suggested in patients
      taking a combined treatment of antipsychotic and antidepressant agents.

PMID- 15845139
TI  - Annals of General Psychiatry.
AB  - Our regular readers will notice that the title of our journal has changed from
      Annals of General Hospital Psychiatry (AGHP) to Annals of General Psychiatry
      (AGP) since January 1st, 2005. This was judged as necessary, in order to be able
      to serve better the aims of the journal. Our initial thoughts were that including
      the term 'General Hospital' in the journal's title would help us to launch a
      journal dedicated to the idea of Psychiatry as a medical specialty. But they were
      not justified; so, now the Annals of General Psychiatry (AGP) is born! It is
      still an Open Access, peer-reviewed, online journal covering the wider field of
      Psychiatry, Neurosciences and Psychological Medicine, and aims at publishing
      articles on all aspects of psychiatry. Primary research articles are the
      journal's priority, and both basic and clinical neuroscience contributions are
      encouraged. The AGP strongly supports and follows the principles of evidence
      based medicine. AGP's articles are archived in PubMed Central, the US National
      Library of Medicine's full-text repository of life science literature, and also
      in repositories at the University of Potsdam in Germany, at INIST in France and
      in e-Depot, the National Library of the Netherlands' digital archive of all
      electronic publications. We hope that the change in the journal's name will cure
      the confusion caused by its previous title and help to achieve the journal's aims
      and scope, that is to help the world-wide promotion of research and publishing in
      the mental health area.

PMID- 15845140
TI  - Psychiatric morbidity of overseas patients in inner London: A hospital based
      study.
AB  - BACKGROUND: Evaluation of the referral, admission, treatment, and outcome of
      overseas patients admitted to a psychiatric hospital in central London. Ethical,
      legal and economic implications, and the involvement of consulates in the
      admission process, are discussed. METHOD: Assessment and review of overseas
      patients admitted between 1 January 1999 and 31 December 1999. Non-parametric
      statistical tests were used, and relevant outcomes described. RESULTS: 19% of
      admissions were overseas patients. Mean age was 38 years. 90% were unattached;
      84% were white, 71% from European countries. 45% spoke fluent English.
      Differences in socio-economic status between home country and England were found.
      74% were unwell on arrival; 65% travelled to England as tourists.65% of
      admissions came via the police. 32% had been ill for more than one year before
      admission; 68% had psychiatric history. 77% were admitted and 48% discharged
      under section of the Mental Health Act. 74% had psychotic disorders, all of them
      with positive symptoms. 55% showed little to moderate improvement in mental
      state; 10% were on Enhanced Care Programme Approach. Relatives of 48% of patients
      were contacted.The Hospital repatriated 52% of patients; the Mental Health Team
      followed up 13% of those discharged. The average length of admission was 43.4
      days (range 1-365). Total cost of admissions was GBP350, 600 ($577, 490); average
      individual cost was GBP11, 116 (range GBP200-81, 000). CONCLUSIONS: Mentally ill
      overseas individuals are a vulnerable group that need recognition by health
      organisations to adapt current practice to better serve their needs. The
      involvement of consulates needs further evaluation.

PMID- 15845141
TI  - Review of the use of Topiramate for treatment of psychiatric disorders.
AB  - BACKGROUND: Topiramate is a new antiepileptic drug, originally designed as an
      oral hypoglycaemic subsequently approved as anticonvulsant. It has increasingly
      been used in the treatment of numerous psychiatric conditions and it has also
      been associated with weight loss potentially relevant in reversing weight gain
      induced by psychotropic medications. This article reviews pharmacokinetic and
      pharmacodynamic profile of topiramate, its biological putative role in treating
      psychiatric disorders and its relevance in clinical practice. METHODS: A
      comprehensive search from a range of databases was conducted and papers
      addressing the topic were selected. RESULTS: Thirty-two published reports met
      criteria for inclusion, 4 controlled and 28 uncontrolled studies. Five
      unpublished controlled studies were also identified in the treatment of acute
      mania. CONCLUSIONS: Topiramate lacks efficacy in the treatment of acute mania.
      Increasing evidence, based on controlled studies, supports the use of topiramate
      in binge eating disorders, bulimia nervosa, alcohol dependence and possibly in
      bipolar disorders in depressive phase. In the treatment of rapid cycling bipolar
      disorders, as adjunctive treatment in refractory bipolar disorder in adults and
      children, schizophrenia, posttraumatic stress disorder, unipolar depression,
      emotionally unstable personality disorder and Gilles de la Tourette's syndrome
      the evidence is entirely based on open label studies, case reports and case
      series. Regarding weight loss, findings are encouraging and have potential
      implications in reversing increased body weight, normalisation of glycemic
      control and blood pressure. Topiramate was generally well tolerated and serious
      adverse events were rare.

PMID- 15845142
TI  - Validation and test-retest reliability of the Royal Free Interview for Spiritual
      and Religious Beliefs when adapted to a Greek population.
AB  - BACKGROUND: The self-report version of the Royal Free Interview for Religious and
      Spiritual Beliefs has been confirmed as a valid and reliable scale, assessing the
      manner and nature in which spiritual beliefs are expressed. The aim of the
      present study was to evaluate the test-retest reliability and psychometric
      properties of the Greek version of the Royal Free Interview for Religious and
      Spiritual Beliefs. METHODS: A total of 209 persons (77 men and 132 women) with a
      mean age of 28.33 +/- 9.44 years participated in the study (test group). We
      subsequently approached 139 participants of the test group with a mean age of
      28.93 +/- 9.60 years, who were asked to complete the Royal Free Questionnaire a
      second time two weeks later (retest group). RESULTS: The vast majority of
      participants (58.9%) reported both a religious and a spiritual belief, compared
      to 52 (25.1%) who told of a religious belief only. The internal consistency of
      the spiritual scale for the test group proved to be good, as standardized inter
      item reliability / Cronbach's alpha was 0.83. Item-total correlations ranged from
      0.51 to 0.73. They indicated very good levels of differentiation, thus showing
      that the questions were appropriate. Internal consistency of the spiritual scale
      for the retest group proved as good as for the test group. Standardized inter
      item reliability / Cronbach's alpha was 0.84. Item-total correlations ranged from
      0.52 to 0.75. The Pearson correlation coefficient for the total test-retest score
      of the spiritual scale was 0.754 (p < 0.001). CONCLUSION: The Greek version of
      the Royal Free Interview for Religious and Spiritual Beliefs is reliable and thus
      suitable for use in Greece.

PMID- 15845143
TI  - Is there a dysfunction in the visual system of depressed patients?
AB  - BACKGROUND: The aim of the current study was to identify a possible locus of
      dysfunction in the visual system of depressed patients. MATERIALS AND METHODS:
      Fifty Major Depressive patients aged 21-60 years and 15 age-matched controls took
      part in the study The diagnosis was obtained with the SCAN v 2.0. The
      psychometric assessment included the HDRS, the HAS, the Newcastle Scales, the
      Diagnostic Melancholia Scale and the GAF scale. Flash Electroretinogram and
      Electrooculogram were performed in all subjects. The statistical analysis
      included ANCOVA, Student's t-test and Pearson Product Moment Correlation
      Coefficient were used. RESULTS: The Electro-oculographic findings suggested that
      all subtypes of depressed patients had lower dark trough and light peak values in
      comparison to controls (p < 0.001), while Arden ratios were within normal range.
      Electroretinographic recordings did not reveal any differences between patients
      and controls or between subtypes of depression. DISCUSSION: The findings of the
      current study provide empirical data in order to assist in the understanding of
      the international literature and to explain the mechanism of action of therapies
      like sleep deprivation and light therapy.

PMID- 15845144
TI  - Compulsory and recommended vaccination in Italy: evaluation of coverage and non
      compliance between 1998-2002 in Northern Italy.
AB  - BACKGROUND: Since vaccinations are an effective prevention tool for maintaining
      the health of society, the monitoring of immunization coverage allows us to
      identify areas where disease outbreaks are likely to occur, and possibly assist
      us in predicting future outbreaks. The aim of this study is the investigation of
      the coverage achieved for compulsory (diphtheria, tetanus, polio, hepatitis B,)
      and recommended (pertussis, Haemophilus influenzae, measles-mumps-rubella)
      vaccinations between 1998 and 2002 in the municipality of Bologna and the
      identification of the subjects not complying with compulsory and recommended
      vaccinations. METHODS: The statistics regarding vaccinal coverage were elaborated
      from the data supplied by the Bologna vaccinal registration system (1998-2000)
      and the IPV4 program (2001-2002). To calculate the coverage for compulsory
      vaccinations and cases of non-compliance reference was made to the protocol drawn
      up by the Emilia Romagna Regional Administration. The reasons for non-compliance
      were divided into various categories RESULTS: In Bologna the levels of
      immunization for the four compulsory vaccinations are satisfactory: over 95%
      children completed the vaccinal cycle, receiving the booster for anti-polio
      foreseen in their 3rd year and for anti-diphtheria, tetanus, pertussis at 6
      years. The frequency of subjects with total non-compliance (i.e. those who have
      not begun any compulsory vaccinations by the age of one year) is generally higher
      in Bologna than in the region, with a slight increase in 2002 (2.52% and 1.06% in
      the city and the region respectively). The frequency of the anti-measles
      vaccination is higher than that of mumps and rubella, which means that the single
      vaccine, as opposed to the combined MMR (measles-mumps-rubella) was still being
      used in the period in question. The most common reason for non compliance is
      objection of parents and is probably due to reduction of certain diseases or
      anxiety about the possible risks. CONCLUSION: In Bologna the frequency of
      children aged 12 and 24 months who have achieved compulsory vaccination varied,
      in 2002, between 95% and 98%. As regards recommended vaccinations the percentage
      of coverage against Haemophilus influenzae is 93.3%, while the levels for
      measles, mumps and pertussis range from 84% to approx. 92%. Although these
      percentages are higher if compared to those obtained by other Italian regions,
      every effort should be made to strengthen the aspects that lead to a successful
      vaccinal strategy.

PMID- 15845145
TI  - Stereophysicochemical variability plots highlight conserved antigenic areas in
      Flaviviruses.
AB  - BACKGROUND: Flaviviruses, which include Dengue (DV) and West Nile (WN), mutate in
      response to immune system pressure. Identifying escape mutants, variant progeny
      that replicate in the presence of neutralizing antibodies, is a common way to
      identify functionally important residues of viral proteins. However, the
      mutations typically occur at variable positions on the viral surface that are not
      essential for viral replication. Methods are needed to determine the true targets
      of the neutralizing antibodies. RESULTS: Stereophysicochemical variability plots
      (SVPs), 3-D images of protein structures colored according to variability, as
      determined by our PCPMer program, were used to visualize residues conserved in
      their physical chemical properties (PCPs) near escape mutant positions. The
      analysis showed 1) that escape mutations in the flavivirus envelope protein are
      variable residues by our criteria and 2) two escape mutants found at the same
      position in many flaviviruses sit above clusters of conserved residues from
      different regions of the linear sequence. Conservation patterns in T-cell
      epitopes in the NS3- protease suggest a similar mechanism of immune system
      evasion. CONCLUSION: The SVPs add another dimension to structurally defining the
      binding sites of neutralizing antibodies. They provide a useful aid for
      determining antigenically important regions and designing vaccines.

PMID- 15845146
TI  - Clinically diagnosed childhood asthma and follow-up of symptoms in a Swedish case
      control study.
AB  - BACKGROUND: Childhood asthma has risen dramatically not only in the western
      societies and now forms a major and still increasing public health problem. The
      aims of this study were to follow up at the age of ten the patterns of asthma
      symptoms and associations among children with a clinically diagnosed asthma in a
      sizeable urban-rural community and to in compare them with demographic controls
      using a standardised questionnaire. METHODS: In a defined region in Sweden with a
      population of about 150,000 inhabitants, all children (n = 2,104) born in 1990
      were recorded. At the age of seven all primary care and hospital records of the
      1,752 children still living in the community were examined, and a group of
      children (n = 191) was defined with a well-documented and medically confirmed
      asthma diagnosis. At the age of ten, 86 % of these cases (n = 158) and controls
      (n = 171) completed an ISAAC questionnaire concerning asthma history, symptoms
      and related conditions. RESULTS: Different types of asthma symptoms were highly
      and significantly over-represented in the cases. Reported asthma heredity was
      significantly higher among the cases. No significant difference in reported
      allergic rhinitis or eczema as a child was found between cases and controls. No
      significant difference concerning social factors or environmental exposure was
      found between case and controls. Among the control group 4.7 % of the parents
      reported that their child actually had asthma. These are likely to be new asthma
      cases between the age of seven and ten and give an estimated asthma prevalence
      rate at the age of ten of 15.1 % in the studied cohort. CONCLUSION: A combination
      of medical verified asthma diagnosis through medical records and the use of self
      reported symptom through the ISAAC questionnaire seem to be valid and reliable
      measures to follow-up childhood asthma in the local community. The asthma
      prevalence at the age of ten in the studied birth cohort is considerably higher
      than previous reports for Sweden. Both the high prevalence figure and allowing
      the three-year lag phase for further settling of events in the community point at
      the complementary roles of both hospital and primary care in the comprehensive
      coverage and control of childhood asthma in the community.

PMID- 15845147
TI  - Development and preliminary evaluation of the VPS ReplaySuite: a virtual double
      headed microscope for pathology.
AB  - BACKGROUND: Advances in computing and telecommunications have resulted in the
      availability of a range of online tools for use in pathology training and quality
      assurance. The majority focus on either enabling pathologists to examine and
      diagnose cases, or providing image archives that serve as reference material.
      Limited emphasis has been placed on analysing the diagnostic process used by
      pathologists to reach a diagnosis and using this as a resource for improving
      diagnostic performance. METHODS: The ReplaySuite is an online pathology software
      tool that presents archived virtual slide examinations to pathologists in an
      accessible video-like format, similar to observing examinations with a double
      headed microscope. Delivered through a customized web browser, it utilises PHP
      (Hypertext PreProcessor) to interact with a remote database and retrieve data
      describing virtual slide examinations, performed using the Virtual Pathology
      Slide (VPS). To demonstrate the technology and conduct a preliminary evaluation
      of pathologists opinions on its potential application in pathology training and
      quality assurance, 70 pathologists were invited to use the application to review
      their own and other pathologists examinations of 10 needle-core breast biopsies
      and complete an electronic survey. 9 pathologists participated, and all
      subsequently completed an exit survey. RESULTS: Of those who replayed an
      examination by another pathologist, 83.3% (5/6) agreed that replays provided an
      insight into the examining pathologists diagnosis and 33.3% (2/6) reconsidered
      their own diagnosis for at least one case. Of those who reconsidered their
      original diagnosis, all re-classified either concordant with group consensus or
      original glass slide diagnosis. 77.7% (7/9) of all participants, and all 3
      participants who replayed more than 10 examinations stated the ReplaySuite to be
      of some or great benefit in pathology training and quality assurance. CONCLUSION:
      Participants conclude the ReplaySuite to be of some or of great potential benefit
      to pathology training and quality assurance and consider the ReplaySuite to be
      beneficial in evaluating the diagnostic trace of an examination. The ReplaySuite
      removes temporal and spatial issues that surround the use of double-headed
      microscopes by allowing examinations to be reviewed at different times and in
      different locations to the original examination. While the evaluation set was
      limited and potentially subject to bias, the response of participants was
      favourable. Further work is planned to determine whether use of the ReplaySuite
      can result in improved diagnostic ability.

PMID- 15845148
TI  - The Arabidopsis AtRaptor genes are essential for post-embryonic plant growth.
AB  - BACKGROUND: Flowering plant development is wholly reliant on growth from
      meristems, which contain totipotent cells that give rise to all post-embryonic
      organs in the plant. Plants are uniquely able to alter their development
      throughout their lifespan through the generation of new organs in response to
      external signals. To identify genes that regulate meristem-based growth, we
      considered homologues of Raptor proteins, which regulate cell growth in response
      to nutrients in yeast and metazoans as part of a signaling complex with the
      target of rapamycin (TOR) kinase. RESULTS: We identified AtRaptor1A and
      AtRaptor1B, two loci predicted to encode Raptor proteins in Arabidopsis.
      Disruption of AtRaptor1B yields plants with a wide range of developmental
      defects: roots are thick and grow slowly, leaf initiation and bolting are delayed
      and the shoot inflorescence shows reduced apical dominance. AtRaptor1A AtRaptor1B
      double mutants show normal embryonic development but are unable to maintain post
      embryonic meristem-driven growth. AtRaptor transcripts accumulate in dividing and
      expanding cells and tissues. CONCLUSION: The data implicate the TOR signaling
      pathway, a major regulator of cell growth in yeast and metazoans, in the
      maintenance of growth from the shoot apical meristem in plants. These results
      provide insights into the ways in which TOR/Raptor signaling has been adapted to
      regulate plant growth and development, and indicate that in plants, as in other
      eukaryotes, there is some Raptor-independent TOR activity.

PMID- 15845149
TI  - Endometriosis in adolescence: a long-term follow-up fecundability assessment.
AB  - OBJECTIVE: A long-term, follow-up study comparing mild and severe forms of
      endometriosis and their fecundability, on 28 women diagnosed with endometriosis
      in adolescence. METHODOLOGY: Twenty-eight patients were identified from a
      prospective cohort of 52 adolescents (ages 12 to 18 years) with operative
      diagnosis of endometriosis between July 1993 and December 1995. All patients
      presented with chronic pelvic pain unresponsive to conservative medical
      management. Diagnosis of pregnancy was made by sonographic identification of
      intrauterine pregnancy, positive serum human chorionic gonadotropin or
      pathological confirmation of products of conception. Patients were categorized as
      fertile or sub-fertile by having > 12 months of unprotected intercourse without
      conception. Follow-up was done for 8.6 years. RESULTS: Staging of endometriosis
      was performed according to the American Society for Reproductive Medicine
      standards. Stage I = 14.3%; Stage II = 39.3%; Stage III = 42.8%; Stage IV = 3.6%.
      Fecundability rates in each stage were statistically significant: Stage I (75%),
      Stage II (55%), Stage III (25%), Stage IV (0%) (p < .05). Rates of spontaneous
      abortion were not statistically significant. CONCLUSION: In our cohort, even at
      the earliest point in the natural life cycle of endometriosis there is an inverse
      relationship between stage of disease at diagnosis and fecundability.

PMID- 15845150
TI  - Frequency of alcohol use and obesity in community medicine patients.
AB  - BACKGROUND: Obesity is an important public health problem. However, the effects
      of alcohol use on the risk for obesity have not been thoroughly explored. This
      study focuses on how frequency of alcohol use is related to the risk of obesity
      in a community medicine clinic population. METHODS: This study used a cross
      sectional survey to test the hypothesis that obesity (BMI > 30) is associated
      with alcohol use. The convenience sample was drawn from three clinics that
      primarily serve low-income populations. Independent variables included frequency
      of alcohol use, frequency of binge drinking, demographic characteristics, health
      behaviors and health status. RESULTS: In comparison to non-drinkers, people who
      consumed alcohol 3 or more days per month had lower odds of being obese (Adjusted
      Odds Ratio = .49, p < .04). As expected, there was a significant association
      between watching eight or more hours of television per day and obesity (AOR =
      2.34, p < .01). CONCLUSION: More frequent drinking and less television time are
      independently associated with reduced odds of obesity in this sample of community
      medicine patients. Additional research is needed to isolate casual mechanisms.

PMID- 15845152
TI  - Normative angiographic data relating to the dimensions of the aorta and pulmonary
      trunk in children and adolescents.
AB  - BACKGROUND: Definition of normative data of the great arteries from neonatal to
      adult ages may aid in assessment of the growth of cardiovascular structures, thus
      guiding the timing and type of intervention in patients with congenital cardiac
      disease. METHODS: We calculated the cross-sectional areas of the arterial roots
      at the basal attachment of the valvar leaflets, the sinuses, and standardized
      distal sites using cineangiograms of 59 normal children and adolescents with mean
      age of 5.4 plus or minus 4.7 years and a range from 0.1 to 16 years, the children
      having a mean weight of 21.2 plus or minus 15.7 kilograms, with a range from 2.2
      to 68 kilograms, and mean height of 108 plus or minus 35 centimetres, with a
      range from 43 to 184 centimetres. Values at each site were calculated averaging
      end-diastolic and end-systolic measurements, and indexed to body surface area.
      Results are expressed as the mean plus or minus the standard deviation. RESULTS:
      The diameter of the aortic root at the basal attachment of the leaflets was 249
      plus or minus 26, the midpoint of the sinuses 379 plus or minus 59, the
      sinutubular junction 290 plus or minus 58, the isthmus 158 plus or minus 36, the
      postisthmic region 152 plus or minus 33, and the descending aorta at the level of
      diaphragm 130 plus or minus 18 millimetres squared per metre squared. The
      pulmonary root measured at the basal attachment of the leaflets was 253 plus or
      minus 28, the midpoint of the sinuses 352 plus or minus 58, the sinutubular
      junction 293 plus or minus 58, the right pulmonary artery 176 plus or minus 25,
      the left pulmonary artery 153 plus or minus 20, and sum of right and left
      pulmonary arteries 330 plus or minus 37 millimetres squared per metre squared.
      All indexes were consistent over a wide range for body surface areas.
      CONCLUSIONS: Definition of normative data of the great vessels may aid in the
      evaluation of congenital or acquired abnormalities, serving as guidelines for
      intervention during medical or surgical management and follow-up.

PMID- 15845153
TI  - What do parents know about the malformations afflicting the hearts of their
      children?
AB  - Traditionally, medical professionals have entrusted the parents of children with
      chronic illness with the task of imparting knowledge about the illness to the
      children. This practice assumes that parents understand the illness, and that
      they pass on their knowledge in a manner appropriate for the individual child.
      The aim of our study was to assess the knowledge that parents of children with a
      cardiac defect have about the malformation in the heart of their child. We sent a
      modified version of the Leuven questionnaire to 350 families. The questionnaire
      was filled in and sent back to our centre by 148 families. Parents showed a good
      knowledge of the name and anatomical characteristics of the cardiac disease
      suffered by their child. Parents with a child taking drugs were not very
      knowledgeable about the regime, side effects, and interaction with other drugs or
      food. Only one-quarter of the parents knew the definition of endocarditis,
      although almost two-fifths were aware that unexplained fever for more than 5 days
      was the most typical symptom. Less than half of the parents knew that
      endocarditis could recur. About two-fifths of parents knew the real possibility
      of their child being involved in competitive sports; but almost half of parents
      were unable to answer this question. The poor knowledge about particular aspects
      of the disease, treatment, and preventive measures revealed by our parents may
      have major consequences. The results of our study are relevant to general daily
      clinical practice.

PMID- 15845154
TI  - Cerebrovascular events in young adults after surgical repair of tetralogy of
      Fallot.
AB  - Increasing numbers of children who have undergone intracardiac repair of
      tetralogy of Fallot have survived to adulthood, but often have residual
      haemodynamic and/or electrical abnormalities. We report the unusual observation
      of 4 instances of cerebrovascular accidents in young adults subsequent to
      surgical repair of tetralogy of Fallot.

PMID- 15845155
TI  - Living with congenital or acquired cardiac disease in childhood: maternal
      perceptions of the impact on the child and family.
AB  - AIMS: Firstly to assess maternal perceptions of the impact of congenital or
      acquired cardiac disease on the child, parents, and siblings, and secondly to
      determine whether there were differences between different diagnostic groups, or
      between those with and without other health problems, with a view to informing
      the development of a cardiac liaison nursing service for children. METHODS: A
      postal survey of 447 families of children with congenital or acquired cardiac
      disease. RESULTS: Completed questionnaires were received from 209 (46.8 percent)
      families. The cardiac lesion was perceived to have a negative impact on many
      areas of family life for about one fifth of the sample, particularly in those
      families where the child was perceived to be more ill. Family relationships,
      however, were affected in a very different way, with 43 percent reporting that
      family members had become closer, and only 8 percent that they had been "pulled
      apart" by the condition of their child. There were a number of differences in the
      perceived impact of the cardiac malformation on school and family life between
      children with different diagnoses, with this being particularly evident for
      families of the patients who had undergone transplantation. When the sample was
      divided according to the presence or absence of other problems with health,
      however, many of these differences between the diagnostic groups disappeared.
      CONCLUSIONS: Irrespective of the severity of the disease, the presence of a
      cardiac malformation has an impact on everyday life for a significant number of
      children and families, particularly if associated with other problems with
      health. Implications for targeting resources to reduce morbidity in these
      children and families are discussed.

PMID- 15845156
TI  - Risk factors for augmentation of the flow of blood to the lungs in pulmonary
      atresia with intact ventricular septum after radiofrequency valvotomy.
AB  - Some patients with pulmonary atresia with an intact ventricular septum, mild to
      moderate right ventricular hypoplasia, and a patent infundibulum remain duct
      dependent on the flow of blood through the arterial duct despite adequate relief
      of the obstruction within the right ventricular outflow tract. The objective of
      our study was to review the risk factors for stenting of the patent arterial
      duct, or construction of a Blalock-Taussig shunt, in the patients with pulmonary
      atresia and an intact ventricular septum who remain duct-dependent following
      radiofrequency valvotomy and dilation of the imperforate pulmonary valve. We
      reviewed the data from 53 patients seen between November 1995 and December 2001.
      Of the 47 patients who survived, 6 required stenting of the patent arterial duct,
      while 4 needed construction of a modified Blalock-Taussig shunt to augment the
      flow of blood to the lungs at a mean of 7 plus or minus 5.7 days following the
      initial intervention. The remaining 37 patients required no additional
      procedures. We compared the findings in these two groups. The mean diameter of
      the tricuspid valve in the patients requiring early reintervention was 8.5 plus
      or minus 3.7 millimetres, giving a Z-score of -1.1 plus or minus 1.47, whilst
      those in the group without early reintervention had values of 10.7 plus or minus
      2.2 millimetres, giving a Z-score of -0.58 plus or minus 1.18 (p equal to 0.003).
      No statistically significant differences were found in right ventricular
      morphology, McGoon ratio, or residual obstruction across the right ventricular
      outflow tract after decompression of the right ventricle. The diameter of the
      tricuspid valve, therefore, appears to be the only factor predicting the need for
      augmentation of flow of blood to the lungs. As just over one-fifth of our
      survivors required such augmentation, we hypothesize that stenting of the patent
      arterial duct may be performed as an integral part of primary transcatheter
      therapy in patients with pulmonary atresia and intact ventricular septum who have
      moderate right ventricular hypoplasia and a small tricuspid valve.

PMID- 15845157
TI  - Comparison of segmental and global systemic ventricular function at rest and
      during dobutamine stress between patients with transposition and congenitally
      corrected transposition.
AB  - The aim of the study was to evaluate segmental and global right ventricular
      function at rest and during stress in patients having a systemic morphologically
      right ventricle. We studied 17 patients after atrial correction for
      transposition, 13 with congenitally corrected transposition, and 11 age-matched
      controls using cardiovascular magnetic resonance at rest and during stress with
      dobutamine given at 15 micrograms per kilogram per minute. Blood was drawn to
      obtain levels of brain natriuretic peptide. Right ventricular ejection fraction
      was calculated, and wall-motion and wall-thickening were assessed, in 4 segments
      of a midventricular slice. The findings for the systemic right ventricle were
      compared to the left ventricle in controls. Patients with transposition showed a
      decreased ejection fraction at rest (57 percent versus 69 percent, p equal to
      0.005), decreased wall motion of the anterior, lateral and septal wall (p less
      than 0.01, p less than 0.01, and p less than 0.01) and decreased thickening of
      the lateral wall (p less than 0.01). Patients with congenitally corrected
      transposition showed normal ejection fraction, wall thickening, and wall motion
      at rest. During dobutamine stress, we found no significant differences in wall
      motion and thickening between the two groups. Ejection fraction, also increased
      to comparable values during stress, at 67 percent versus 66 percent, p not being
      significant. In both groups, we observed similarly increased levels of brain
      natriuretic peptide (p equal to 0.02 and 0.03, respectively). We conclude that
      only patients with transposition showed segmental wall motion and wall thickening
      abnormalities at rest. After dobutamine stress, however, segmental and global
      right ventricular dysfunction was similar in both groups.

PMID- 15845158
TI  - Non-invasive assessment of right ventricular function in the late follow-up of
      the Senning procedure.
AB  - Deteriorating ventricular function is a major concern after the Senning
      operation. A Doppler-derived non-geometric measurement, the so-called myocardial
      performance index, has been described for use in adults and children. We aimed to
      assess the utility of this index as a method for quantification of right
      ventricular function in patients in the late follow-up of the Senning procedure,
      and to correlate the right ventricular ejection fraction and the first derivative
      of right ventricular pressure as derived using echocardiography with the ejection
      fraction determined using magnetic resonance imaging. We studied 44 patients
      within a mean postoperative period of 15.3 years. We calculated the right
      ventricular myocardial performance index by pulsed wave Doppler interrogation of
      tricuspid inflow and aortic outflow, the ejection fraction by Simpson's rule, and
      the first derivative of right ventricular pressure by continuous wave Doppler
      from tricuspid regurgitation. Mean values of right ventricular myocardial
      performance index, ejection fraction, and the first derivative of right
      ventricular pressure were 0.50, 39 percent and 1,398 millimetres of mercury per
      second, respectively. A cut-off value of 0.47 for the right ventricle myocardial
      performance index was determined, with a sensitivity of 75 percent and a
      specificity of 62.5 percent. We found no correlation between ejection fraction
      and the first derivative of right ventricular pressure as estimated by
      echocardiography and the ejection fraction as shown by magnetic resonance imaging
      (r2 equal to 0.29 and 0.04 respectively). We concluded, first, that patients with
      preserved right ventricular function had values for the right ventricular
      myocardial performance index lower than 0.47, and second, that ejection fraction
      and the first derivative of right ventricular pressure as determined
      echocardiographically did not correlate with values derived using magnetic
      resonance imaging.

PMID- 15845159
TI  - Factors affecting left ventricular remodelling and mechanics in the long-term
      follow-up after successful repair of aortic coarctation.
AB  - AIMS: To identify factors predisposing to abnormal left ventricular geometry and
      mechanics in 52 patients after successful repair of aortic coarctation. METHODS
      AND RESULTS: We evaluated left ventricular remodelling, systolic midwall
      mechanics, and isthmic gradient by echo-Doppler, systemic blood pressure at
      rest/exercise and by ambulatory blood pressure monitoring, and the aortic arch by
      magnetic resonance imaging. Echocardiographic findings were compared with those
      of 142 controls. The patients with aortic coarctation showed an increased indexed
      left ventricular end-diastolic volume, increased mass index, increased ratio of
      mass to volume and systolic chamber function. The contractility, estimated at
      midwall level, was increased in 21 percent of the patients. In 26 (50 percent) of
      the patients, we found abnormal left ventricular geometry, with 9 percent showing
      concentric remodelling, 33 percent eccentric hypertrophy, and 8 percent
      concentric hypertrophy. These patients were found to be older, underwent a later
      surgical repair, and to have higher systolic blood pressures at rest and exercise
      as well as during ambulatory monitoring. The relative mural thickness and mass
      index of the left ventricle showed a significant correlation with different
      variables on uni- and multivariate analysis. Age and diastolic blood pressure at
      rest are the only factors associated with abnormal left ventricular remodelling.
      CONCLUSIONS: Patients who have undergone a seemingly successful surgical repair
      of aortic coarctation may have persistently abnormal geometry with a hyperdynamic
      state of the left ventricle. This is more frequent in older patients, and in
      those with higher diastolic blood pressures.

PMID- 15845160
TI  - Current subjective state of health, and longitudinal psychological well-being
      over a period of 10 years, in a cohort of adults with congenital cardiac disease.
AB  - OBJECTIVE: To examine the current subjective state of health, and the
      longitudinal course of psychological well-being, in adult patients with
      congenital cardiac malformations. METHODS: Our study concerns the second follow
      up of a cohort of patients with congenital cardiac malformations. We examined 362
      consecutive patients, aged from 20 to 46 years, who underwent surgical procedures
      for treatment of congenital cardiac disease between 1968 and 1980, specifically
      for treatment of atrial and ventricular septal defects, tetralogy of Fallot,
      transposition, and pulmonary stenosis. The patients were submitted to extensive
      medical and psychological examination. During psychological examination, in which
      all patients were seen by the same psychologist (EvR), patients filled in
      questionnaires concerning their current subjective state of health, using the 36
      item Short Form Health Survey (SF-36), and psychological well-being, answering
      the Heart Patients Psychological Questionnaire. The data we acquired at their
      first follow-up was used to measure the longitudinal course of psychological well
      being over the intervening period of 10 years. RESULTS: When compared to a
      reference group, the patients assessed their state of health less favourably
      concerning physical functioning, but more favourable with regard to social
      functioning, bodily pain, and limitations of role due to emotional problems.
      Younger female patients reported more limitations of role due to physical
      functioning than did the female patients who were older. Patients with
      transposition showed a negative trend for their subjective state of health, but
      reported the least bodily pain. Within the overall group of patients, displeasure
      had increased, while social inhibition had decreased, over the intervening period
      of 10 years. CONCLUSION: Extra attention should be paid to the subjective
      experiences of young female patients with congenital cardiac disease. The
      patients with transposed arterial trunks seem overall to experience poorer
      physical health.

PMID- 15845161
TI  - Anomalous origin of one pulmonary artery from the ascending aorta.
AB  - We describe the surgical repair in three infants presenting with one pulmonary
      artery arising from the ascending aorta, the other artery arising normally from
      the right ventricle via the pulmonary trunk. Repair consisted of reimplantation
      of the anomalous pulmonary artery to the pulmonary trunk, in association with
      repair of associated intracardiac malformations. All patients survived the
      surgical procedures, and were discharged in stable clinical condition.
      Subsequently, two of the three patients developed stenosis at the surgical
      anastomosis relatively early after the initial procedure, and underwent
      reoperation. Although survival after operation is now expected for this
      malformation, reports of late results are lacking. Larger numbers of operations
      are needed before we can reach definitive conclusions. The origin of one branch
      pulmonary artery from the ascending aorta in the presence of a pulmonary valve
      and main pulmonary artery is a very rare congenital cardiac anomaly. PATIENTS AND
      METHODS: Between January 1995 and June 2003, 3 infant girls presented with the
      origin of one branch artery from the ascending aorta, while the other pulmonary
      artery originated from the pulmonary trunk which was in continuity with the right
      ventricular outflow tract. The pulmonary artery that arose from the right
      ventricle was left in 2 and right in 1 patient. RESULTS: At the age 13, 48 and 62
      days respectively, the patients underwent surgical repair consisting with
      reimplantation of the anomalous pulmonary artery branch to the pulmonary trunk in
      association with repair of intracardiac malformations. There were no hospital
      deaths. Postoperative complications included: prolonged intubation in two
      patients (10 and 16 days), low output syndrome in 1 patient, cardiac tamponade in
      1 patient and seizures in 1 patient. All patients were discharged in good
      clinical condition. There have been no late deaths. Subsequently, two of the
      three patients developed stenosis at the surgical anastomosis relatively early
      after the initial procedure, and after unsuccessful balloon dilation, underwent
      surgical reoperation. CONCLUSIONS: Although operative survival is now possible
      for this malformation, reports of late results are lacking. Two of the three
      patients developed stenosis at the surgical anastomosis relatively early after
      surgery. Larger numbers of operations are necessaries to reach definitive
      conclusions.

PMID- 15845162
TI  - Prenatal presentation of an intracardiac infantile type of haemangioendothelioma.

PMID- 15845163
TI  - The large right-sided patent arterial duct: its implications for construction of
      systemic-to-pulmonary anastomoses.

PMID- 15845164
TI  - Thoughts about fixed subaortic stenosis in man and dog.

PMID- 15845165
TI  - Robert Mark Freedom MD, FRCPC, FACC, O. Ont.

PMID- 15845166
TI  - The Ross procedure performed in the setting of congenitally bifoliate aortic
      valve with anomalous right coronary artery.
AB  - We treated successfully using the Ross procedure a 14-year old with a
      congenitally stenotic bifoliate aortic valve associated with anomalous origin of
      the right coronary artery. The anomalous artery arose from the same aortic sinus
      that gave rise to the main stem of the left coronary artery, and reached the
      right atrioventricular groove by traversing the tissue plane between the aortic
      root and the subpulmonary infundibulum. Both coronary arteries were reimplanted
      using a single arterial button.

PMID- 15845167
TI  - Scimitar syndrome associated with absence of the right pulmonary artery and a
      persistent primitive hepatic venous plexus.
AB  - An 18-month-old boy, referred because of an infection of the airways, was found
      to have a right-sided heart, a hypoplastic right lung, absence of the right
      pulmonary artery, and persistence of the hepatic venous plexus. The benign
      association of this unusual variant of the scimitar syndrome and persistence of
      the hepatic venous plexus needs to be recognised in order to avoid extensive
      investigations and surgery involving the inferior caval vein.

PMID- 15845168
TI  - Successful repair of aorto-left ventricular tunnel diagnosed prenatally.
AB  - Aorto-left ventricular tunnels are anomalous communications between the ascending
      aorta and the left ventricle. Prenatal diagnosis, followed by successful surgical
      management, is rare. We describe a fetus diagnosed with aorto-left ventricular
      tunnel at 35 weeks who achieved a favourable outcome after immediate postnatal
      surgical repair.

PMID- 15845169
TI  - Sudden death during a change in treatment for pulmonary hypertension.
AB  - We describe an infant with an atrioventricular septal defect and separate valvar
      orifices for the right and left ventricles, the so-called primum defect, who
      presented with serious pulmonary hypertension. Treatment with sildenafil was
      changed to intravenous epoprostenol due to lack of any measurable effects of the
      initial therapy as shown by echocardiography. The girl died three days after the
      change in treatment. We suggest that a mismatch between ventilation and perfusion
      contributed significantly to her death.

PMID- 15845170
TI  - Myocardial ischaemia in a child infected with influenza B.
AB  - Cardiac involvement is a rare complication of infection by the influenza B virus.
      It usually presents with ventricular dysfunction, arrhythmias, or both. We report
      a 13-year-old boy with clinical, electrocardiographic, and laboratory findings of
      myocardial ischaemia during an otherwise silent acute infection with influenza B.
      Coronary endothelial injury constituted a potential underlying mechanism, and
      microthrombosis was promoted by high levels of lipoprotein(a) in the serum.

PMID- 15845171
TI  - Duplication of the 22q11.2 region associated with congenital cardiac disease.
AB  - The DiGeorge, or velocardiofacial, syndrome has been aetiologically linked to
      heterozygous deletion of the q11.2 region of chromosome 22. It is the most common
      of the microdeletion syndromes, and is associated with malformations involving
      the ventricular outflow tracts. Duplication of the 22q11.2 region has also been
      reported, adding to a growing list of syndromes involving genomic deletion or
      duplication that cause disease by decreasing or increasing the gene dosage. We
      report two cases of congenital cardiac disease associated with microduplications
      of 22q11.2, and discuss the evidence to date for the potential clinical
      significance of this genetic defect.

PMID- 15845175
TI  - Bevacizumab extends survival for patients with nonsquamous non-small-cell lung
      cancer.

PMID- 15845177
TI  - Bevacizumab, when added to paclitaxel/carboplatin, prolongs survival in
      previously untreated patients with advanced non-small-cell lung cancer:
      preliminary results from the ECOG 4599 trial.

PMID- 15845178
TI  - Computer-assisted image analysis of bronchioloalveolar carcinoma.
AB  - In clinical trials, response rate is an important endpoint for assessing the
      efficacy of an anticancer drug. The Response Evaluation Criteria for Solid Tumors
      (RECIST) has been widely used as a standard method to assess response. The RECIST
      requires only 1-dimensional measurement of tumor size. However,
      bronchioloalveolar carcinoma (BAC), which commonly presents as infiltrative or
      micronodular lesions, is not always readily assessable by RECIST. During the past
      2 years, we have been developing computer-based programs to more accurately
      measure tumor size on chest computed tomography (CT) scans. In a first-generation
      computer-assisted image analysis (CAIA) system, we were able to capture and
      quantify lesions on CT scans by linking the software programs of eFilm,
      HyperSnap, and Scion. We have applied this CAIA approach to measuring BAC
      response to gefitinib in the Southwest Oncology Group (S0126) trial. However,
      this first-generation CAIA system involves multiple manual steps and is therefore
      labor intensive. We are now developing a fully automated CAIA program based on a
      versatile software platform, ImageJ, created at the National Institutes of
      Health. Taking theoretical and physical considerations into account, Java plug-in
      programs for ImageJ are created to automatically analyze CT scans in the Digital
      Imaging and Communications in Medicine format. We have demonstrated the
      feasibility of an ImageJ-based automated CAIA program for measuring BAC
      bidimensionally on CT scans. This automated CAIA system will be applied in a
      prospective clinical trial of the GVAX vaccine in patients with BAC.

PMID- 15845179
TI  - Split-course versus continuous thoracic radiation therapy for limited-stage small
      cell lung cancer: final report of a randomized phase III trial.
AB  - The optimal integration of radiation and chemotherapy for limited-stage small
      cell lung cancer (SCLC) remains unclear. This phase III trial was conducted to
      determine whether chemotherapy plus interdigitating split-course thoracic
      radiation therapy (RT) improved survival compared with standard-dose continuous
      thoracic RT. One hundred fourteen patients were randomized to receive 50 Gy
      thoracic RT delivered in 2.0-Gy fractions given continuously (5 weeks) concurrent
      with the first 2 cycles of chemotherapy (arm A) or 50 Gy delivered via an
      interdigitating split course in 2.5-Gy fractions (8 weeks) concurrent with the
      first 3 cycles of chemotherapy (arm B). During the split-course RT, once-daily
      radiation was delivered on days 8-17 of each of the first two 21-day cycles and
      days 8-11 of the third 21-day cycle. All patients received the following
      chemotherapy: cisplatin/etoposide on cycles 1, 2, and 5 and
      cyclophosphamide/vincristine/doxorubicin on cycles 3, 4, and 6. Prophylactic
      cranial irradiation was recommended after a complete response to all therapy. One
      hundred ten eligible patients were randomized. Grade 3/4 esophagitis was reported
      in 9% of patients receiving continuous thoracic RT versus 4% of patients
      receiving split-course RT. Grade 3/4 hematologic toxicity was common in both
      treatment arms. Complete/partial response was observed in 80% of patients on arm
      A versus 84% on arm B. Overall survival rates at 5 years were 18% and 17% for
      arms A and B, respectively. Interdigitating split-course thoracic RT delivered in
      2.5-Gy fractions was tolerable in patients with limited-stage SCLC but did not
      provide a survival advantage.

PMID- 15845180
TI  - Tirapazamine with cisplatin and vinorelbine in patients with advanced non-small
      cell lung cancer: a phase I/II study.
AB  - This phase I/II study was conducted to evaluate the safety and efficacy of
      tirapazamine in combination with cisplatin and vinorelbine for patients with
      advanced-stage IIIB/IV chemonaive non-small-cell lung cancer. Seventy patients
      with a Karnofsky performance status of > or = 60% were included. In the phase I
      part of the study, 21 patients were treated on day 1 with tirapazamine
      (escalating doses of 260, 330, or 390 mg/m(2)), cisplatin (75 or 100 mg/m(2)),
      and vinorelbine (25 or 30 mg/m(2)) for a maximum of 6 cycles every 4 weeks.
      Vinorelbine was repeated every week. In the phase II part of the study, 49
      patients were treated on day 1 with tirapazamine 390 mg/m(2), cisplatin 100
      mg/m(2), and vinorelbine 30 mg/m(2). The maximum tolerated dose was not reached.
      Muscle cramps, vomiting, nausea, tinnitus, neutropenia, and diarrhea were the
      most frequently reported adverse events in the phase I part of the study. Most of
      these events were grade 1 or 2. In the phase II part of the study, response rate
      was 47%, and median survival was 50 weeks. The most frequently reported adverse
      event was neutropenia. Asthenia, fever, anemia, vomiting, weight decrease,
      nausea, and muscle cramps were also noted. For patients treated at the maximum
      dose, dose reductions occurred 14% of tirapazamine cycles and in 4% of cisplatin
      cycles. The median number of cycles was 3. This regimen has a manageable toxicity
      profile. Response rate and median survival suggest that this combination might be
      more active than the cisplatin/vinorelbine combination. This triplet is currently
      being evaluated in a phase III study.

PMID- 15845181
TI  - Clinical significance of hypoxia-inducible factor-1a messenger RNA expression in
      locally advanced non-small-cell lung cancer after platinum agent and gemcitabine
      chemotherapy followed by surgery.
AB  - Hypoxia-inducible factor-1a (HIF-1a) is a key regulator of the angiogenic
      cascade. This study analyzed HIF-1a messenger RNA expression levels using real
      time quantitative polymerase chain reaction (PCR) in paraffin-embedded surgical
      specimens from 54 stage IIB-III patients with non-small-cell lung cancer (NSCLC)
      treated with induction platinum/gemcitabine followed by surgery between September
      1998 and December 2002. Radiographic response was observed in 61% of patients.
      Median survival was 37.8 months. Forty-five patients with complete resection
      attained a 52-month median survival, whereas 8 patients with incomplete resection
      had a 12-month median survival, and 1 unresectable patient had a survival of 14
      months. No significant differences were observed in overall survival (OS) or
      event-free survival (EFS) according to HIF-1a expression levels. Patients were
      divided into quartiles according to HIF-1a gene expression levels. Median EFS for
      the 13 patients in the lowest quartile has not been reached yet, whereas median
      EFS for the 13 patients in the top quartile was 9 months (P = 0.192). Similarly,
      median OS for the 13 patients in the lowest quartile has not been reached yet,
      whereas median OS for the 13 patients in the top quartile was 52 months (P =
      0.297). The cisplatin/gemcitabine combination is highly active in neoadjuvant
      treatment. Hypoxia-inducible factor-1a expression levels analyzed by real-time
      quantitative PCR in surgery specimens after platinum/gemcitabine therapy do not
      correlate with the outcome of patients with stage II/III NSCLC.

PMID- 15845182
TI  - Neoadjuvant chemotherapy followed by late-course accelerated hyperfractionated
      radiation therapy for locally advanced non-small-cell lung cancer: long-term
      results of a phase I/II clinical trial.
AB  - Toxicity, response, and long-term results of a definitive chemotherapy/radiation
      therapy (RT) protocol in patients with unresectable stage III non-small-cell lung
      cancer (NSCLC) were evaluated. Two cycles of cisplatin-based chemotherapy were
      delivered before RT, and another 2 cycles were added for patients who responded
      to the first 2 cycles of chemotherapy. The first course of radiation covered the
      primary lesion and elective nodal regions, given in 2 Gy per fraction, 5 days a
      week for a dose of 40 Gy. Late-course hyperfractionated accelerated RT was
      delivered to the gross tumor twice a day for an additional 27 Gy within 2 weeks,
      using 1.5 Gy per fraction. Fifty-three patients with unresectable stage IIIA (N2)
      and IIIB NSCLC were eligible for analysis. Twelve patients developed grade 3
      neutropenia, and 3 patients developed grade 4 neutropenia. Grade 2 or 3
      esophagitis was observed in 14 and 2 patients, respectively, and grade 2 or 3
      pneumonitis was observed in 9 and 1 patient, respectively. Six patients developed
      grade 2 and 1 patient developed grade 3 late lung toxicity. The median survival
      time was 15.5 months. Twenty-six of 53 patients (49%) have died of locoregional
      progression inside the thorax. The distant metastasis rate was 59.5% (22 of 37
      patients) for those who did not respond to chemotherapy and 18.8% (3 of 16
      patients) for those who responded to chemotherapy (P = 0.006). Late-course
      hyperfractionated accelerated RT combined with induction chemotherapy was well
      tolerated and yielded long-term results that compare favorably with those of
      studies using 2 cycles of induction chemotherapy and conventional fractionated
      RT. However, local control was still discouraging.

PMID- 15845183
TI  - Increased standardized uptake value in the primary lesion predicts nodal or
      distant metastases at presentation in lung cancer.
AB  - Standardized uptake value (SUV) has been linked to tumor aggressiveness and long
      term prognosis. Based on the hypothesis that positron emission tomography (PET)
      SUV serves as a surrogate for biologic aggression, we investigated whether SUV in
      the primary lesion, independent of size, correlates with the presence of nodal or
      distant metastases at the time of presentation. We retrospectively reviewed
      computed tomography (CT) scan, PET scan, and histologic findings of consecutive
      patients in our lung cancer referral population evaluated between December 15,
      2000 and April 15, 2004. Only patients with primary non-small-cell lung cancer
      and pathologic confirmation of nodal status or conventionally accepted non-PET
      proof of distant metastases were included for analysis. One hundred thirty-nine
      patients had complete results, including CT, PET, and independent confirmation of
      nodal or distant disease. The stage distribution was as follows: 33 IA, 24 IB, 5
      IIA, 9 IIB, 21 IIIA, 8 IIIB, and 39 IV. Simple logistic regression analysis
      demonstrated a highly significant correlation between SUV of the primary lesion
      and the presence of nodal or distant metastases at the time of presentation (P =
      0.0036). When odds ratios were calculated, a 13% increase in the likelihood of
      nodal/distant disease was found for every unit increase in SUV. We conclude that
      PET SUV, independent of size, is a marker of biologic aggression. Elevated SUV in
      the primary lesion at presentation should prompt high suspicion and mandates
      meticulous search for nodal or distant disease.

PMID- 15845184
TI  - Role of zoledronic acid in the setting of bone metastases from non-small-cell
      lung cancer.
AB  - Bone metastases are major sequelae of non-small-cell lung cancer and are
      associated with poor survival, skeletal-related events (SREs), and economic
      burden. In recent phase III trials, zoledronic acid has demonstrated a potential
      to prevent or delay SREs, although this has not yet translated into a survival
      benefit. Zoledronic acid is the first and only bisphosphonate with proven
      efficacy in the treatment of bone metastases associated with a broad range of
      tumors, including lung cancer. We report herein a case study that highlights the
      clinical benefit of zoledronic acid in a patient with squamous cell carcinoma of
      the lung.

PMID- 15845185
TI  - Treatment considerations for head and neck cancer in the elderly.
AB  - As life expectancy increases, surgeons can expect an increasing number of
      geriatric patients. In turn, the number of elderly patients presenting with head
      and neck cancer is likely to increase. Management of this subpopulation has
      become a source of debate because there is a paucity of randomized data regarding
      the effect of age on treatment response and morbidity associated with the
      treatment of head and neck cancer. The management of head and neck cancer in the
      elderly depends on the patient's age and general condition, the stage of disease,
      the effects of treatment on quality of life (such as speech and swallowing),
      patient and family wishes, and active physician participation in continued care.
      Elderly patient's comorbid conditions need appropriate attention especially if
      surgery is to be undertaken. The aim of this review is to examine the current
      literature in an attempt to develop an approach to the treatment of the elderly
      patient with head and neck cancer and to define the pertinent issues that require
      further study.

PMID- 15845186
TI  - A review of ENT consultant postal questionnaires.
AB  - In recent years, there appears to have been an increase in the number of postal
      questionnaires being received by ENT consultants. Questionnaires with unsound
      methodology waste the time of those who send and receive them, as inferences
      cannot be made from their results. In this study,a review was performed on a
      sample of 19 questionnaire studies published in two ENT journals between January
      1998 and December 2002. Each study was given a 30-point score, based on the
      quality of its methodology. The average score assigned to each study was 32
      percent, suggesting that the quality of methodology was generally poor. These
      results should serve as a warning to those embarking on and those interpreting
      research of this kind.

PMID- 15845187
TI  - Constitutive (HO-2) and inducible (HO-1) haem oxygenase in pleomorphic adenomas
      of the human parotid: an immunocytochemical study.
AB  - This study examines the expression HO-1 and HO-2 isozymes in human parotid
      pleomorphic adenomas. They are members of the heat shock protein family, and are
      thought to play a role in the regulation of tumoral blood flow.
      Immunocytochemistry using antibodies specific for HO-1 and HO-2 were undertaken
      in 12 pleomorphic adenoma specimens, all sections of which contained adjacent
      normal salivary tissue. Normal salivary gland acini and ducts displayed
      significantly stronger immunoreactivity for HO-2 compared to tumour cells (p <
      0.001). Expression for HO-1 was minimal in both normal salivary gland acini and
      tumour cells with no difference (p = 1.000). However, positive staining for HO-1
      was seen in normal salivary ducts and in pleomorphic adenomas showing ductal
      differentiation. In conclusion, this is the first study to examine the expression
      of HO-1 and HO-2 within normal salivary glands and pleomorphic adenomas. Our
      findings suggest that HO may be implicated in the pathogenesis of salivary
      pleomorphic adenomas.

PMID- 15845188
TI  - An analysis of diagnostic delay in unilateral facial paralysis.
AB  - Bell's palsy or idiopathic facial palsy is the commonest cause of unilateral
      lower motor neuron facial palsy. Misdiagnosis of facial nerve palsy as Bell's
      palsy is still seen in clinical practice. The clinician should always consider
      the possibility of a potentially serious underlying pathology before making the
      diagnosis of Bell's palsy. We present a series of 13 patients referred to our ENT
      department with an initial diagnosis of Bell's palsy. Further clinical
      examination and investigation revealed the underlying cause. Many had additional
      symptoms and signs related to the ear. In all patients with unilateral facial
      palsy a detailed history should be taken and thorough clinical examination
      carried out. Where no recovery occurs within the expected time period further
      radiological investigations such as computerized axial tomography (CT) and
      magnetic resonance imaging (MRI) should be performed. Current scanning techniques
      provide good quality images, which can show occult lesions of the temporal bone,
      internal acoustic canal and/or cerebellopontine angle. Radiologists with a
      special interest and experience in otoneurological radiology should ideally
      report these images, and a close co-operation between ENT surgeon and radiologist
      is essential in arriving at a proper diagnosis.

PMID- 15845189
TI  - A study of chorda tympani nerve injury and related symptoms following middle-ear
      surgery.
AB  - This is a prospective study that looks into the prevalence of chorda tympani
      nerve (CTN) injury and related symptoms following varying degrees of trauma to
      the nerve during three common types of middle-ear operation: myringoplasty,
      tympanotomy and mastoidectomy. The number of patients with CTN-related symptoms
      varied widely between the three groups. Increased occurrence of the nerve related
      symptoms and a prolonged recovery time were observed in the tympanotomy group.
      Stretching of the nerve produced more symptomatic cases than cutting it in the
      myringoplasty and mastoidectomy groups. Recovery was complete in 92 percent of
      the symptomatic patients by 12 months. It is important to inform patients about
      the possibility of CTN injury during middle-ear operations, and it should also be
      emphasized that symptoms related to CTN injury can occur irrespective of the type
      of damage to the nerve.

PMID- 15845190
TI  - Correlation between bacteriology and computed tomography staging for chronic
      sinusitis.
AB  - In this study we report on the correlation between bacteriology and disease
      severity staging by computed tomography (CT) for chronic sinusitis. When patients
      with chronic sinusitis underwent functional endoscopic sinus surgery (FESS), swab
      specimens were taken from the ipsilateral middle meati and ethmoid sinuses under
      endoscope guidance. The severity of chronic sinusitis was evaluated by pre
      operative CT scans. The CT scans were staged by the Lund and Mackay system. The
      scores for the frontal, anterior ethmoid and maxillary sinuses and for the
      ostiomeatal complex were added. The culture rates were correlated with the added
      scores. Between November 1998 and January 2003, 79 pairs of specimens were
      collected from 79 patients whose CT scans were done within a day before FESS. The
      culture rates of middle-meatus specimens were moderately correlated with the
      scores, but those of ethmoid sinus specimens were negatively correlated with the
      scores. If Staphylococcus epidermidis and corynebacteria were considered normal
      flora, the bacteriology of the middle meatus was highly correlated with the CT
      scores. This study shows that culture rates of middle-meatal specimens tended to
      increase with the severity of chronic sinusitis.

PMID- 15845191
TI  - Tea tree oil: in vitro efficacy in otitis externa.
AB  - OBJECTIVE: The purpose of this study was to determine the susceptibility of
      organisms causing otitis externa (OE) to the essential oil of Melaleuca
      alternifolia, or tea tree oil (TTO). METHODS: Fifty-seven swabs were taken from
      the ears of 52 patients with OE for culture and sensitivity. A broth
      microdilution method was used to determine the minimum inhibitory concentration
      (MIC) of TTO for each organism. RESULTS: In 51 percent of the swabs taken,
      pathogenic organisms were cultured. Of these cultures 71 percent, both bacteria
      and yeast, were susceptible to TTO 2 percent or less. The only organism showing
      resistance to TTO was Pseudomonas aeruginosa; however 25 percent of these
      bacteria were sensitive. CONCLUSION: Tea tree oil may have a role to play in the
      treatment of OE. However, more work needs to be done to enhance the anti
      pseudomonal effect and to assess ototoxicity.

PMID- 15845193
TI  - Securing tracheal stents: a new and simple method.
AB  - Indwelling silastic stents have been used in the subglottis and upper trachea to
      manage laryngotracheal abnormalities. A number of methods of fixation have been
      described. The authors describe a quick and simple method of fixing endoluminal
      tracheal stents using a single suture.

PMID- 15845192
TI  - A study of out-of-hours facilities in otolaryngology: current provision and
      problems.
AB  - 'Action on ENT' has recently published advice as to the minimum requirements for
      equipment required to provide a safe and suitable out-of-hours service in ENT.
      Our objectives were to determine the availability of a dedicated ENT treatment
      room for seeing patients out of hours, appropriately maintained specialized ENT
      equipment and availability of appropriate assistance. In addition, the mechanism
      for disinfection of nasoendoscopes out of hours was determined. Telephone
      questionnaires of 106 ENT units in England, which provide an out-of-hours ENT
      service, were taken. At each unit the standard questionnaire was answered by the
      first on-call ENT doctor. One hundred and one units (95 percent) had access to a
      dedicated treatment room out of hours. The number of units with a microscope was
      91 (86 percent), headlight/lamp and mirror was 105 (99 percent), flexible
      nasoendoscope was 86 (81 percent) and cautery (electrical or chemical) was 105
      (99 percent). Seventy-nine units (75 percent) found that their treatment rooms
      were adequately stocked, and 62 units (58 per cent) had assistance available when
      needed. Twenty-four units (23 percent) sterilized their scopes adequately, 22
      units (21 percent) used endosheaths, 26 units (24 percent) used a variety of
      inadequate cleaning methods, and 34 respondents (32 percent) were unsure how
      their scopes were cleaned. This survey has shown that not all ENT units have
      appropriately equipped out-of-hours facilities. There is a need for nationally
      agreed guidelines stating the minimum equipment and assistance required to
      provide a safe, adequate and suitable out-of-hours service. National guidelines
      on out-of-hours disinfection of flexible nasoendoscopes are also required.

PMID- 15845194
TI  - Obstructive sleep apnoea associated with congenital choanal atresia.
AB  - We report here a very rare case of bilateral congenital choanal atresia untreated
      for the 27 years after birth. A 27-year-old Japanese man complaining of long-term
      nasal obstruction, snoring and daytime sleepiness visited our hospital. He
      exhibited the characteristic appearances of long face and bilateral hypoplastic
      cheeks. Examination by flexible fiberscopy and computed tomography led us to
      diagnose him with bilateral choanal atresia. Subsequent polysomnography revealed
      the number of apnoea or hypopnoea episodes per hour (apnoea-hypopnoea index, or
      AHI) to be over 10. On the basis of these observations, we modified the diagnosis
      to obstructive sleep apnoea syndrome (OSAS) secondary to congenital choanal
      atresia.

PMID- 15845195
TI  - Jejunal free-flap reconstruction complicated by development of post-irradiation
      sarcoma: what information should patients receive about the long-term effects of
      radiotherapy for head and neck tumours?
AB  - Jejunal free-flap reconstruction is a well recognized, reliable technique
      commonly used for reconstruction of the upper aero-digestive tract following
      surgery for malignancy, and radiotherapy is commonly used as an adjuvant
      treatment in such cases. Unfortunately, post-irradiation sarcomas are a well
      recognized complication of radiotherapy and generally have a poor prognosis. We
      report what we believe to be the first case of radiation-induced sarcoma in a
      free-flap jejunal graft and discuss the information that should be given to
      patients undergoing radiotherapy to head and neck tumours.

PMID- 15845196
TI  - Lymphoma mimicking a thyroglossal duct cyst in an adolescent.
AB  - Mass lesions of the head and neck in infants and children can be either
      developmental, inflammatory or neoplastic. Lymphomas (Hodgkin's or Non-Hodgkin's)
      commonly present as neck lumps in children. Although malignancy is not the
      commonest aetiology of paediatric cervical lumps, a high index of suspicion is
      critical to facilitate early diagnosis and treatment of cervical lesions. We
      present the case of a 15-year-old boy who presented with a solitary midline
      cervical lesion, which simulated a thyroglossal cyst on clinical examination.
      However, histopathological examination revealed it to be a Hodgkin's lymphoma.
      Related literature is also reviewed.

PMID- 15845197
TI  - Inflammatory pseudotumour of the neck with multifocal sites on positron emission
      tomography scan imaging.
AB  - We present a patient with an inflammatory pseudotumour of the neck with
      multifocal sites in the head and chest responding to steroids. A review of the
      literature revealed that this is the first case of a pseudotumour with multiple
      sites in the head and neck as revealed by 2-[18]fluorodeoxyglucose (FDG) PET scan
      imaging.

PMID- 15845198
TI  - Autologous replacement of the vocal fold: a new surgical approach for adduction
      type spasmodic dysphonia.
AB  - Many surgical approaches have been developed for the treatment of adduction-type
      spasmodic dysphonia (SPD). We developed and performed a new type of surgical
      approach (autologous replacement of the vocal fold). Our new surgical technique
      increases the advantages and decreases the disadvantages of previous surgical
      procedures in three ways: (1) It has similar effects to the previous procedures
      in that it prevents contraction of the thyroarytenoid muscle. (2) It decreases
      vocal-fold tension, as in framework surgery. (3) It reduces glottal incompetence,
      as does fibrinogen-glue injection, but it is more suitable because it is
      autologous. Furthermore, it produces increases in the mass and volume of the
      vocal-fold body and is also safe because the replacement tissue is autologous.
      The short-term results appear encouraging in preventing spastic voice while also
      avoiding vocal-fold atrophy. Long-term follow up will be necessary to determine
      the actual efficacy. However, this is clearly a possible choice as a surgical
      approach for treating adduction-type SPD.

PMID- 15845199
TI  - Pleomorphic adenoma and severe obstructive sleep apnoea.
AB  - Two cases of deep lobe parotid tumours extending into the parapharyngeal space
      and causing obstructive sleep apnoea are described. Post-operatively, marked
      improvements in nocturnal hypoxic episodes and the symptoms of obstructive sleep
      apnoea were seen. Although minor salivary gland pleomorphic adenomas have been
      described as a cause of airway compromise, pleomorphic adenomata arising from the
      deep lobe of the parotid, causing proven obstructive sleep apnoea, have not
      previously been documented. The anatomy and common pathologies of the
      parapharyngeal space are discussed.

PMID- 15845200
TI  - Simultaneous tumours of the larynx with the same histology: a case report and
      review of the literature.
AB  - Synchronous laryngeal malignancies are extremely uncommon. To the best of our
      knowledge, only four cases of primary synchronous squamous cell carcinoma (SCC)
      of the larynx are available in the literature. We report the case of a 52-year
      old patient with simultaneous spindle-cell carcinoma and SCC in situ of the
      larynx. The pathogenesis, treatment and prognosis of this rare occurrence have
      been discussed.

PMID- 15845201
TI  - Thoracic ranula: an extremely rare case.
AB  - We present the first case of a thoracic ranula which originated from the left
      submandibular area extending into the subcutaneous tissue planes of the anterior
      chest wall. The patient had a history of surgery for a previous benign left
      salivary gland cyst, and presented with an enlarging mass in the anterior chest
      wall. This was a recurrence of a ranula, with an extension into the anterior
      thoracic wall. The thoracic ranula was excised, together with ipsilateral
      sublingual and submandibular glands, via a transcervical approach. No recurrence
      was detected over a 3-year post-operative follow up.

PMID- 15845202
TI  - Emergency tracheal catheterization for jet ventilation: a role for the ENT
      surgeon?
AB  - Stridor causing respiratory failure is an ENT and anaesthetic emergency requiring
      prompt management to secure a clear airway. We describe a case of subacute
      partial upper airway obstruction due to a large laryngeal carcinoma in an 81-year
      old male resulting in respiratory failure. The patient became apnoeic after
      gaseous induction of general anaesthesia, and after two failed intubation
      attempts an emergency transtracheal airway catheter was placed by the surgeon
      under direct vision below the cricothyroid membrane, as this had tumour
      involvement. The patient was subsequently manually jet-ventilated with ease until
      a formal tracheostomy was made. Where difficulties with tracheal anatomy are
      encountered due to the presence of pathology, the insertion of a temporary airway
      catheter for jet ventilation by the surgeon can buy valuable time and be life
      saving.

PMID- 15845203
TI  - Previously treated oesophageal achalasia re-presenting with stridor.
AB  - Achalasia is a motility disorder of the oesophagus that typically presents with
      dysphagia, regurgitation and chest pain. A rare presenting symptom is stridor. A
      case of previously treated achalasia re-presenting with stridor is described and
      associated imaging presented.

PMID- 15845204
TI  - Antibiotic prophylaxis in clean neck dissections.

PMID- 15845206
TI  - Hypothermia as a neuroprotective strategy in subarachnoid hemorrhage: a
      pathophysiological review focusing on the acute phase.
AB  - Aneurysmal subarachnoid hemorrhage (SAH) remains a very prevalent challenge in
      neurosurgery associated with a high morbidity and mortality due to the lack of
      specific treatment modalities. The prognosis of SAH patients depends primarily on
      three factors: (i) the severity of the initial bleed, (ii) the endovascular or
      neurosurgical procedure to occlude the aneurysm and (iii) the occurrence of late
      sequelae, namely delayed ischemic neurological deficits due to cerebral
      vasospasm. While neurosurgeons and interventionalists have put significant
      efforts in minimizing periprocedural complications and a multitude of
      investigators have been devoted to the research on chronic vasospasm, the acute
      phase of SAH has not been studied in comparable detail. In various experimental
      studies during the past decade, hypothermia has been shown to reduce neuronal
      damage after ischemia, traumatic brain injury and other cerebrovascular diseases.
      Clinically, only some of these encouraging results could be reproduced. This
      review analyses results of studies on the effects of hypothermia on SAH with
      special respect to the acute phase in an experimental setting. Based on the
      available data, some considerations for the application of mild to moderate
      hypothermia in patients with subarachnoid hemorrhage are given.

PMID- 15845207
TI  - Local brain hypothermia for neuroprotection in stroke treatment and aneurysm
      repair.
AB  - Hypothermia is well known to provide neuroprotection following various brain
      insults in experimental animals. Two recently completed clinical trials of whole
      body hypothermia in out-of-hospital cardiac arrest patients' demonstrated
      significantly improved survival rates and neurologic outcomes. These results
      provide new excitement and encouragement for clinical application of hypothermia
      in cerebrovascular disease. However, the intensive care challenges and adverse
      events (e.g. prolonged times to target temperatures, shivering and sedation,
      pneumonia) during the management of hypothermia, dampen enthusiasm for widespread
      application especially in elderly stroke patients. In this manuscript, we review
      recent hypothermia trials for stroke. We describe an alternate approach, i.e.
      local brain cooling, and discuss this new technique with reference to the
      extensive literature on the marked efficacy of hypothermia. We describe a new
      technology, the ChillerPad(TM) and ChillerStrip(TM) Systems developed by Seacoast
      Technologies, Inc. (Portsmouth, NH, USA). The latter device has received FDA
      approval and will be employed in a trial of local hypothermia for cerebral
      aneurysm repair. We present our experimental findings that profound local
      hypothermia does not damage cortical neurons. We also report that local
      hypothermia protects the blood-brain barrier and markedly reduces vasogenic edema
      development in an experimental intracerebral hemorrhage model. Lastly, we review
      potential mechanisms through which hypothermia provides blood-brain barrier
      protection and reduces edema formation. Clearly, hypothermia has a bright future
      for cerebrovascular disease treatment if brain cooling can be delivered in a
      manner that does not compromise the patient or the neurosurgical and intensive
      care settings. Local brain cooling may be just that new treatment approach.

PMID- 15845208
TI  - Pathophysiology of an hypoxic-ischemic insult during the perinatal period.
AB  - Hypoxia-ischemia is a leading cause of morbidity and mortality in the perinatal
      period with an incidence of 1/4000 live births. Biochemical events such as energy
      failure, membrane depolarization, brain edema, an increase of neurotransmitter
      release and inhibition of uptake, an increase of intracellular Ca(2+), production
      of oxygen-free radicals, lipid peroxidation, and a decrease of blood flow are
      triggered by hypoxia-ischemia and may lead to brain dysfunction and neuronal
      death. These abnormalities can result in mental impairments, seizures, and
      permanent motor deficits, such as cerebral palsy. The physical and emotional
      strain that is placed on the children affected and their families is enormous.
      The care that these individuals need is not only confined to childhood, but
      rather extends throughout their entire life span, so it is very important to
      understand the pathophysiology that follows a hypoxic-ischemic insult. This
      review will highlight many of the mechanisms that lead to neuronal death and
      include the emerging area of white matter injury as well as the role of
      inflammation and will provide a summary of therapeutic strategies. Hypothermia
      and oxygen will also be discussed as treatments that currently lack a specific
      target in the hypoxic/ischemic cascade.

PMID- 15845209
TI  - Ischemic preconditioning procedure induces behavioral deficits in the absence of
      brain injury?
AB  - Preconditioning describes a phenomenon whereby a sub-injury inducing insult can
      protect against a later larger injury. Thus, short-term cerebral ischemia can
      protect against a prolonged ischemia (ischemic preconditioning). This study
      examines rats undergoing ischemic preconditioning to test whether preconditioning
      may cause changes in behavior even though they do not cause an identifiable brain
      lesion. Rats had a transient (15 minutes) middle cerebral artery occlusion or a
      sham occlusion. Forelimb placing and forelimb use asymmetry tests were used to
      assess behavioral deficits. Brain histology, microglia activation, heat shock
      protein and ferritin levels were also examined. Ischemic preconditioning did not
      cause brain infarction, but induced behavioral changes. There were no significant
      differences between ischemic preconditioning and sham rats in the two behavioral
      tests at day one. However, the ischemic preconditioning group showed impaired
      forelimb placing at days 3, 7 and 14 (p<0.05). That group also had a significant
      (p<0.05) behavioral deficit in the forelimb use asymmetry test at days 3 and 7
      (but not 14). Our present study demonstrated that a behavioral deficit occurred
      in ischemic preconditioning. This raises the question of whether induction of
      protective mechanisms by preconditioning stimuli necessarily involves some form
      of brain injury, detectable by changes in behavior though not by a lesion. This
      would be consistent with data suggesting that brain injury can initiate
      mechanisms potentially favorable to neuroplasticity and neuroprotection.

PMID- 15845210
TI  - New horizons for primary intracerebral hemorrhage treatment: experience from
      preclinical studies.
AB  - Intracerebral hemorrhage (ICH) remains a major medical problem, for which there
      is no effective treatment. However, extensive experimental and clinical research
      carried out in recent years has brought to light new exciting ideas for novel
      potential treatments. First, it was well documented that the management of
      hypertension helps to prevent new and recurrent ICH. Also, development of new
      guidelines for management of hypertension after the onset of the ICH may help in
      more effective ICH treatment. Existing contemporary data collected from
      preclinical studies indicates that ICH-induced inflammation represents a key
      factor leading to secondary brain damage, suggesting that some anti-inflammatory
      approaches can be used to treat hemorrhagic stroke. In this article, beyond
      discussing implications related to hypertension, we will summarize important (but
      not all) new discoveries connecting the role of inflammation to ICH pathology.
      Selected aspects of inflammatory response including the role of cytokines,
      transcription factor nuclear factor-kB, microglia activation, astrogliosis, and
      complement activation will be introduced. We will also discuss the role for
      reactive oxygen species and metalloproteinases in ICH pathogenesis and introduce
      basic knowledge on the nature of ICH-induced cell death including apoptosis.
      Potential targets for intervention and translation will be discussed.

PMID- 15845211
TI  - The role of Na-K-Cl co-transporter in cerebral ischemia.
AB  - The electroneutral Na-K-Cl co-transporter (NKCC) protein transports Na(+), K(+)
      and Cl(-) into cells under physiological conditions with a stoichiometry of
      1Na(+) :1K(+) :2Cl(-). NKCC is characteristically inhibited by the
      sulfamoylbenzoic acid "loop'' diuretics, such as bumetanide and furosemide. To
      date, only two distinct isoforms, NKCC1 and NKCC2, have been identified. NKCC1
      has a broad tissue distribution, while the NKCC2 isoform is only found in
      vertebrate kidney. NKCC serves multiple functions, including ion and fluid
      movements in secreting or reabsorbing epithelia and cell volume regulation.
      However, understanding the role of NKCC1 in the central nervous system has just
      begun. NKCC1 protein is expressed in neurons throughout the brain. Dendritic
      localization of NKCC1 is found in both pyramidal and non-pyramidal neurons. NKCC1
      is important in the maintenance of intracellular Cl(-) in neurons and contributes
      to GABA-mediated depolarization in immature neurons. Thus, NKCC1 may affect
      neuronal excitability through regulation of intracellular Cl(-) concentration.
      Expression of NKCC1 protein has also been found in astrocytes and
      oligodendrocytes. In addition to its role in the accumulation of Cl(-), NKCC1 may
      also contribute to K(+) clearance and maintenance of intracellular Na(+) in glia.
      Our recent studies suggest that NKCC1 activation leads to high [K(+)](o(-))
      induced astrocyte swelling and glutamate release, as well as neuronal Na(+) , and
      Cl(-) influx during acute excitotoxicity. Inhibition of NKCC1 activity
      significantly reduces infarct volume and cerebral edema following cerebral focal
      ischemia.

PMID- 15845212
TI  - Neuroprotective herbs for stroke therapy in traditional eastern medicine.
AB  - Traditional Eastern Medicine (TEM) has a long history in stroke therapy and its
      therapeutic efficacy has been confirmed by clinical studies. Extensive experience
      and abundant clinical data on TEM in stroke treatment have been accumulated over
      the past thousand years. Basic and clinical research in TEM constitutes a
      potentially rich source for new drug discovery and development with the
      integration of TEM and Western pharmacology. In recent years, many attempts have
      been made to document research data from extracts of composite formulas, single
      herbs, or single compounds from TEM herbs, according to orthodox pharmacological
      actions. This article reviews herbs and prescriptions that have been documented
      to have a neuroprotective effect in in vitro and in vivo ischemic model systems,
      and the neuroprotective compounds isolated from them. I also discuss the
      neuroprotective mechanisms of prescriptions, herbs, and single compounds relevant
      to the treatment of brain ischemia, including anti-oxidant, anti-excitotoxic, and
      anti-inflammatory effects.

PMID- 15845213
TI  - Eye movements in patients with Neglect show space-centred attention when fixating
      rotating objects.
AB  - OBJECTIVES AND METHODS: To determine whether attention operates in space-based or
      object-based coordinates, Neglect patients were confronted with a rotating
      object. After the object had undergone a 180-degree rotation a stimulus appeared
      on either side of the object and the reaction times were measured. The results of
      the present study showed that all patients performed worse on the contralateral
      side, both in the static as well as in the moving condition. This supports the
      theory that attention operates in space-centred reference frames. To bring some
      light into the discussion, the recording of eye movements was included. RESULTS:
      Our results showed three effects: (1) most eye movements started to the right of
      the midline; (2) some patients followed the moving object to the mid-line, before
      they returned to the ipsi-lesional side; (3) some patients followed the complete
      movement of the barbell. CONCLUSION: It is argued that patients recovering from
      Neglect consciously make more eye movements to the left to compensate for the
      deficit, but attention remains in the ipsi-lesional field.

PMID- 15845214
TI  - Influence of repetitive transcranial magnetic stimulation on disease severity and
      oxidative stress markers in the cerebrospinal fluid of patients with
      spinocerebellar degeneration.
AB  - Ataxia severity, cerebellar hemispheric blood flow (CHBF), ascorbate free radical
      (AFR), superoxide dismutase protein, superoxide scavenging activity, and 8
      hydroxy-2'-deoxyguanosine (8-OHdG) in cerebrospinal fluid (CSF) were compared
      before and after an 8-week course of repetitive transcranial magnetic stimulation
      (rTMS) in 20 patients with spinocerebellar degenerations (SCD). SCD patients
      showed higher AFR, 8-OHdG, and superoxide scavenging activity than 19 controls.
      In SCD patients, AFR and ataxia severity declined, and CHBF increased after rTMS.
      As the SCD patients showed negative correlations between ataxia severity and CHBF
      or superoxide scavenging activity, the therapeutic mechanism of rTMS may involve
      decreased oxidative stress and increased CHBF.

PMID- 15845215
TI  - Predictive factors for intracerebral hemorrhage in patients with cavernous
      angiomas.
AB  - OBJECTIVES: Prediction of intracerebral hemorrhage (ICH) in patients with
      cavernous angiomas is not totally elucidated. The aims of our study were to
      determine the rate of cerebral hemorrhage, its associated factors, and the
      clinical outcome in patients with cavernous angiomas in a Hispanic population.
      METHODS: We studied 133 patients with cavernous angiomas. The patients were
      classified into two groups depending on whether they presented an ICH. A
      comparative analysis of demographics and clinical data, neuroimaging
      characteristics, and prognosis was carried out in patients with and without
      hemorrhage. The hemorrhage rate (expressed as the percentage per patient per
      year) was also estimated. RESULTS: Seventy-eight patients (59%) had hemorrhage.
      Non-lobar location of angiomas was associated with hemorrhage [OR 4.82 (CI 95%
      2.17-10.73; p=<0.001)]. In contrast, factors associated with a decreased risk of
      hemorrhage were a family history of epilepsy [OR 0.30 (CI 95% 0.10-0.79;
      p=0.016)] and lobar location of the angiomas [OR 0.21 (CI 95% 0.09-0.46;
      p=<0.001)]. The hemorrhagic rate of 1.71% per patient per year was influenced by
      the location. It was only 1.22% per patient per year in lobar angiomas and 2.33,
      2.39, and 2.82% per patient per year for brainstem, cerebellum, and deep
      hemispheric angiomas, respectively. CONCLUSIONS: The non-lobar location of
      cavernous angiomas gives a higher risk of hemorrhage in our Mexican mestizo
      population, without the hemorrhage being related to either age or sex.

PMID- 15845216
TI  - The effect of laser irradiation for nucleus pulposus: an experimental study.
AB  - BACKGROUND: The radicular pain caused by disc herniation can be explained by two
      mechanisms: the compression of the nerve root by the herniated disc or the
      irritation of the nerve root due to chemical factors. Percutaneous laser disc
      decompression (PLDD) was introduced for the treatment of lumbar disc hernias in
      the 1980s. Decompression of the nerve root is assumed to be an effective
      therapeutic mechanism for PLDD. However, laser irradiation might reduce the
      chemical factors that cause nerve root irritation by altering intra-disc
      proteins. We used nerve conduction velocities (NCV) and levels of two chemical
      factors to evaluate the differences between the two groups in this in vivo study.
      METHODS: All rabbits had the nerve root in contact with the leakage from the
      nucleus pulposus. One group underwent laser irradiation for the leaking nucleus
      pulposus including the incision site of the disc and nucleus pulposus itself. The
      levels of two chemical factors, prostaglandin E2 and phospholipase E2, in the
      intervertebral disc were measured before and after laser irradiation. RESULTS:
      NCV in the laser-irradiated group was significantly faster than in the non-laser
      irradiated group. The levels of chemical factors were significantly reduced after
      laser irradiation. CONCLUSIONS: One of the mechanisms thought to be responsible
      for PLDD's effectiveness is a decrease in the chemical factors through protein
      alteration in the intervertebral disc by laser irradiation.

PMID- 15845217
TI  - Clinical and histological features of multiple meningiomas compared with solitary
      meningiomas.
AB  - Between 1991 and 2002, 456 patients with an intracranial meningioma were treated.
      Thirty-nine of these had more than one meningioma (8.6%). The mean age was 58
      years (27-85 years). Sex distribution was 8.8:1 (35 female, four male). There was
      no associated spinal meningioma. No patient had neurofibromatosis. In 19 patients
      all meningiomas were removed. Twelve showed the same histology, seven had
      different histological features. In the remaining 20 patients only the
      symptomatic meningioma was removed. Recurrences occurred in 11 patients (28.2%).
      Six patients died during follow-up. Multiple meningiomas have their own clinical
      features. Besides a high female preponderance, PR expression was stronger in
      multiple meningiomas than in solitary meningiomas while p53 status and MIB-1 LI
      were similar between the two groups. Progesterone receptor, p53 status and MIB-1
      LI were valuable markers for predicting a patient's outcome in multiple
      meningiomas. The number of meningiomas is growing in patients with recurrent
      meningiomas.

PMID- 15845218
TI  - Bone-like polyethelyne burr-hole cover.
AB  - OBJECTIVE: Several materials are available for covering burr holes but none of
      them are ideal with respect to biocompatibility, strength and morbidity. With
      these properties in mind, our objective was to design a porous polyethylene
      device, which looked like bone and provides protection and cosmesis while being
      quick and easy to apply. METHODS AND MATERIALS/RESULTS: A burr-hole cover was
      created to cover small cranial defects and craniostomies. Using high-density
      polyethylene, this cover was designed to resemble the bony structure of the
      skull. Its porous architecture allows for tissue ingrowth and bony integration.
      It consists of a cylinder which fits into the burr hole and a cap which can be
      sutured or anchored with titanium screws. CONCLUSIONS: The "bone-like" burr-hole
      cover provides adequate protection, biocompatibility and cosmesis and is simple
      to use. Alternative implants can be toxic to surrounding tissues, costly and time
      consuming to apply. This high-density polyethylene cover is compatible with
      surrounding tissue as well as being of a porous nature and the material it is
      made from offers high tensile strength for adequate protection.

PMID- 15845219
TI  - Mitochondrial mutagenesis and oxidative stress in human prostate cancer.
AB  - Prostate cancer is the most common cancer diagnosed in men in the United States,
      but the primary cause and the molecular events leading to prostate carcinogenesis
      are poorly understood. Using the approach of laser capture microdissection, we
      revealed extensive somatic mitochondrial DNA (mtDNA) mutations in prostatic
      neoplastic lesions. Inspection of the lesion associated mutations not only
      provided new insights into the genetics of prostate cancer, but also revealed new
      patterns of mtDNA mutation in prostate carcinogenesis. Further analysis on a high
      frequency of multiple mutational events observed in the same neoplastic lesion
      revealed an unusually rapid process in mitochondrial mutagenesis, suggesting a
      new process of mitochondrial hyper-mutagenesis in cancer cells, likely mediated
      by cellular oxidative stress. Thus, active mitochondrial mutagenesis in prostate
      cancer suggests a prominent role of increased cellular oxidative stress in
      neoplastic transformation and the increased susceptibility of neoplastic cells to
      oxidative damage.

PMID- 15845221
TI  - Rodent carcinogenicity of peroxisome proliferators and issues on human relevance.
AB  - A variety of substances such as hypolipidemic drugs, phthalate ester
      plasticizers, pesticides, and industrial solvents have been shown to increase the
      size and number of peroxisomes in rats and mice. They are grouped under the
      generic term peroxisome proliferators (PP) because of their unique property of
      inducing peroxisome proliferation. There are marked species differences in
      response to PP. Rats and mice are most sensitive, and hamsters show an
      intermediate response while guinea pigs, monkeys, and humans appear to be
      relatively insensitive or non-responsive at dose levels that produce a marked
      response in rodents. Out of over 100 PP identified to date, about 30 have been
      adequately tested and shown to be carcinogenic, inducing tumors (primarily in the
      liver) upon chronic administration to rats and/or mice; hence, chemicals which
      induce the proliferations of peroxisomes have formed a unique class of chemical
      carcinogens. It is not well documented that activation of the "peroxisome
      proliferator-activated receptor alpha" (PPARalpha) is involved in PP-induced
      liver growth and carcinogenesis in rodents. PPARalpha is also present in human
      cells; however, the levels reported are about 10% of those found in the liver of
      rodents. The human relevance of rodent tumors induced by PP has been the subject
      of debate over the last decade. Review of the existing evidence on PPAR-alpha
      agonists by a recent International Life Science Institute (ILSI) workgroup
      following a human relevance mode of action (MOA) framework has concluded that
      despite the presence of similar pathways in humans, it is unlikely that the
      proposed MOA for rodent tumors is plausible in humans, taking into account
      kinetic and dynamic factors. The data, however, did not permit a definitive
      conclusion that the animal MOA is not plausible in humans. While these agents
      appear unlikely to be hepatocarcinogens in humans at expected levels of human
      exposure, it remains uncertain to some experts in the field whether there is no
      possibility of carcinogenic potential under any circumstances of PP exposure, and
      if the potential human carcinogenicity of these chemicals can be summarily
      ignored. A number of remaining issues on human relevance of rodent tumors induced
      by PP are discussed.

PMID- 15845220
TI  - Epidemiologic studies of PCB congener profiles in North American fish consuming
      populations.
AB  - Long range atmospheric and stream transport and oceanic currents drive the
      ecologic process of PCB deposition in the abiotic environment. In contrast short
      range transport via bioaccumulation-biomagnification up the food chain determines
      PCB congener profiles and concentrations and their adverse effects in biological
      organisms. Two research approaches to congeners, with potential to associate
      specific adverse human health effects with PCB concentrations in indigenous small
      populations, are summarized in this study. The field epidemiological approach
      includes giving questionnaires to target population groups in conjunction with
      sampling for PCBs (and selected persistent organic pollutants and metals), in
      foods purchased or hunted and collected by Inuit peoples. Direct determination of
      contaminant levels in food sources and among individuals in selected comparative
      subpopulations is also presented.

PMID- 15845222
TI  - Colon cancer: prevalence, screening, gene expression and mutation, and risk
      factors and assessment.
AB  - Colon cancer detection at an early stage and identifying susceptible individuals
      can result in reduced mortality from this prevalent cancer. Genetic events
      leading to the development of this cancer involve a multistage progression of
      adenoma polyps to invasive metastatic carcinomas. Currently, there is no
      satisfactory screening method that is highly specific, sensitive, or reliable.
      Dietary patterns associated with the greatest increase in colon cancer risk are
      the ones that typify a diet rich in fat and calories, and low in vegetable,
      fruits, and fibers. Genetic susceptibility to environmental carcinogenesis must
      be factored into the risk assessment for this cancer. Many genes have been shown
      to be associated with increased expression and mutations in colorectal cancer
      patients. These genes have been reviewed; it is hoped that by carefully selecting
      a number of them, a molecular approach that is suitable for arriving at a
      tumorigenic expression index is developed, which will reliably detect this cancer
      at an early stage (i.e., before it metastasizes), especially in exfoliated
      samples (e.g., stool and blood), so that appropriate intervention strategies can
      be implemented. Illustrated herein is the utility of employing real-time reverse
      transcriptase polymerase chain reaction (RT-PCR) to quantitatively measure gene
      expression, and develop an index that is specific for this cancer, which if
      perfected may result in a reliable and sensitive screening technique for
      colorectal cancer detection.

PMID- 15845223
TI  - Aromatic amines and biomarkers of human exposure.

PMID- 15845224
TI  - Photoreaction, phototoxicity, and photocarcinogenicity of retinoids.
AB  - Sunlight is a human carcinogen. Many retinoid-containing cosmetics are used to
      protect damages caused by sunlight irradiation. Since retinol is thermally
      unstable and retinyl palmitate (RP) s relatively more stable, RP is also widely
      used as an ingredient in cosmetic formulations. In general, little is known about
      the photodecomposition of retinoids and the toxicity of retinoids and their
      photodecomposition products on the skin's responses to sunlight. This review
      focuses on the update information on photoreactions, phototoxicity, and
      photocarcinogenicity of the natural retinoids including retinol, retinal,
      retinoid acid (RA), retinyl acetate, and RP.

PMID- 15845226
TI  - Emergence of Salmonella epidemics: the problems related to Salmonella enterica
      serotype Enteritidis and multiple antibiotic resistance in other major serotypes.
AB  - Two major changes in the epidemiology of salmonellosis occurred in the second
      half of the 20th century: the emergence of food-borne human infections caused by
      S. Enteritidis and by multiple-antibiotic resistant strains of Salmonella. This
      review updates information on the S. Enteritidis pandemic and focuses on the
      emergence of Salmonella, carrying the SGI1 antibiotic resistance gene cluster,
      resistant to extended-spectrum cephalosporins, or resistant to fluoroquinolones.
      The factors responsible for the emergence of these Salmonella strains could be
      either of human origin or related to bacterial genome evolution. However, our
      increasing understanding of the molecular fluidity of the genome shows that any
      attempt to counteract bacteria results in further bacterial evolution or
      adaptation of other bacteria to take place in the new free ecological niche. In
      these conditions, we can ask who is faster: humans who want to eliminate
      bacterial pathogens or bacteria that continuously evolve to gain new niches.

PMID- 15845227
TI  - Enterohaemorrhagic Escherichia coli: emerging issues on virulence and modes of
      transmission.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) constitute a subset of serotypes (E.
      coli O157 and some other serogroups) of Shiga toxin (Stx)-producing E. coli
      (STEC) firmly associated with severe human illnesses like bloody diarrhoea and
      haemolytic uraemic syndrome. Stx production is essential but not sufficient for
      EHEC virulence. Most strains are capable of colonising the intestinal mucosa of
      the host with the "attaching and effacing" mechanism, genetically governed by a
      large pathogenicity island (PAI) defined as the Locus of Enterocyte Effacement.
      Other virulence factors carried by mobile genetic elements like PAI and plasmids
      have been recently described, and their role in the pathogenic process has not
      been fully elucidated. EHEC are zoonotic pathogens. They rarely cause disease in
      animals, and ruminants are recognised as their main natural reservoir. Cattle are
      considered to be the most important source of human infections with EHEC O157,
      and the ecology of the organism in cattle farming has been extensively studied.
      The organism has also been reported in sheep, goats, water buffalos, and deer.
      Pigs and poultry are not considered to be a source of EHEC and the sporadic
      reports may derive from accidental exposure to ruminant dejections. The
      epidemiology of EHEC infections has remarkably changed during the past ten years
      and an increasing number of unusual food vehicles have been associated with human
      infections. New routes of transmission have emerged, like contact with animals
      during farm visits and a wide variety of environment-related exposures. As for
      other zoonotic agents, having animals and raw products that are free from EHEC is
      not possible in practice. However, their occurrence can be minimised by applying
      high standards of hygiene in all the steps of the food production chain.

PMID- 15845228
TI  - From the discovery of the Malta fever's agent to the discovery of a marine mammal
      reservoir, brucellosis has continuously been a re-emerging zoonosis.
AB  - Brucellosis is not a sustainable disease in humans. The source of human infection
      always resides in domestic or wild animal reservoirs. The routes of infection are
      multiple: food-borne, occupational or recreational, linked to travel and even to
      bioterrorism. New Brucella strains or species may emerge and existing Brucella
      species adapt to changing social, cultural, travel and agricultural environment.
      Brucella melitensis is the most important zoonotic agent, followed by Brucella
      abortus and Brucella suis. This correlates with the fact that worldwide, the
      control of bovine brucellosis (due to B. abortus) has been achieved to a greater
      extent than the control of sheep and goat brucellosis (due to B. melitensis),
      these latter species being the most important domestic animals in many developing
      countries. The long duration and high cost of treatment of human brucellosis
      reduces the efficacy of the therapy. There is no human vaccine for brucellosis
      and the occurrence of brucellosis is directly linked to the status of animal
      brucellosis in a region. In this context, the Word Health Organization has
      defined the development of a human vaccine, besides the implementation of control
      and eradication programs in animals, as a high priority. The pathogenicity for
      humans of B. suis biovars 1, 3 and 4 is well established, whereas B. suis biovar
      2 seems to be less pathogenic. Indeed, although hunters and pig farmers have
      repeatably experienced infectious contact with B. suis biovar 2 (found in wild
      boar and outdoor-rearing pigs in Europe), isolation of B. suis biovar 2 from
      human samples have only been seldom reported. Marine mammal brucellosis, due to
      two new proposed Brucella species i.e. B. cetaceae and B. pinnipediae, represents
      a new zoonotic threat but the pathogenicity for humans of the different Brucella
      species found in cetaceans and pinnipeds still has to be clearly established.

PMID- 15845229
TI  - Is Q fever an emerging or re-emerging zoonosis?
AB  - Q fever is a zoonotic disease considered as emerging or re-emerging in many
      countries. It is caused by Coxiella burnetii, a bacterium developing spore-like
      forms that are highly resistant to the environment. The most common animal
      reservoirs are livestock and the main source of infection is by inhalation of
      contaminated aerosols. Although the culture process for Coxiella is laborious,
      advances on the knowledge of the life cycle of the bacterium have been made. New
      tools have been developed to (i) improve the diagnosis of Q fever in humans and
      animals, and especially animal shedders, (ii) perform epidemiological studies,
      and (iii) prevent the disease through the use of vaccines. This review summarizes
      the state of the knowledge on the bacteriology and clinical manifestations of Q
      fever as well as its diagnosis, epidemiology, treatment and prevention in order
      to understand what factors are responsible for its emergence or re-emergence.

PMID- 15845230
TI  - Campylobacter.
AB  - Species within the genus, Campylobacter, have emerged over the last three decades
      as significant clinical pathogens, particularly of human public health concern,
      where the majority of acute bacterial enteritis in the Western world is due to
      these organisms. Of particular concern are the species, C. jejuni and C. coli,
      which are responsible for most of these gastrointestinal-related infections.
      Although these organisms have already emerged as causative agents of zoonoses,
      several aspects of their epidemiology and pathophysiology are only beginning to
      emerge. Trends in increasing antibiotic resistance are beginning to emerge with
      oral antibiotics, which may be the drug of choice for when it is necessary to
      intervene chemotherapeutically. This review wishes to examine (i) emerging
      clinical aspects of the disease, such as Guillain Barre syndrome (GBS), (ii) the
      association between these organisms and poultry as a natural host, (iii)
      environmental aspects of Campylobacter epidemiology, (iv) the emergence of
      atypical campylobacters (v) emerging trends in antibiotic resistance, (vi)
      adoption of modern methods for the detection of campylobacters.

PMID- 15845231
TI  - Factors associated with the rapid emergence of zoonotic Bartonella infections.
AB  - Within the last 15 years, several bacteria of the genus Bartonella were
      recognized as zoonotic agents in humans and isolated from various mammalian
      reservoirs. Based on either isolation of the bacterium or PCR testing, eight
      Bartonella species or subspecies have been recognized as zoonotic agents,
      including B. henselae, B. elizabethae, B. grahamii, B. vinsonii subsp. arupensis,
      B. vinsonii subsp. berkhoffii, B. grahamii, B. washoensis and more recently B.
      koehlerae. The present manuscript reviews the factors associated with the
      emergence of these zoonotic pathogens, including better diagnostic tools and
      methods to identify these fastidious bacteria, host immunosuppression (caused by
      infectious agents, cancer, aging or induced by immunosuppressive drugs), the
      interaction of co-infection by several infectious agents that may enhanced the
      pathogenecity of these bacteria, increased outdoor activity leading to exposure
      to wildlife reservoirs or vectors, poverty and low income associated with
      infestation by various ectoparasites, such as body lice and finally the dispersal
      of Bartonellae around the world. Furthermore, a description of the main
      epidemiological and clinical features of zoonotic Bartonellae is given. Finally,
      the main means for diagnosis, treatment and prevention of these diseases are
      presented.

PMID- 15845232
TI  - Zoonotic aspects of Mycobacterium bovis and Mycobacterium avium-intracellulare
      complex (MAC).
AB  - Pathogens that are transmitted between the environment, wildlife, livestock and
      humans represent major challenges for the protection of human and domestic animal
      health, the economic sustainability of agriculture, and the conservation of
      wildlife. Among such pathogens, the genus Mycobacterium is well represented by M.
      bovis, the etiological agent of bovine tuberculosis, M. avium ssp.
      paratuberculosis (Map) the etiological agent of Johne disease, M. avium ssp.
      avium (Maa) and in a few common cases by other emergent environmental
      mycobacteria. Epidemiologic surveys performed in Europe, North America and New
      Zealand have demonstrated the existence and importance of environmental and
      wildlife reservoirs of mycobacterial infections that limit the attempts of
      disease control programmes. The aim of this review is to examine the zoonotic
      aspects of mycobacteria transmitted from the environment and wildlife. This work
      is focused on the species of two main groups of mycobacteria classified as
      important pathogens for humans and animals: first, M. bovis, the causative agent
      of bovine tuberculosis, which belongs to the M. tuberculosis complex and has a
      broad host range including wildlife, captive wildlife, domestic livestock, non
      human primates and humans; the second group examined, is the M. avium
      intracellulare complex (MAC) which includes M. avium ssp. avium causing major
      health problems in AIDS patients and M. avium ssp. paratuberculosis the
      etiological agent of Johne disease in cattle and identified in patients with
      Crohn disease. MAC agents, in addition to a broad host range, are environmental
      mycobacteria found in numerous biotopes including the soil, water, aerosols,
      protozoa, deep litter and fresh tropical vegetation. This review examines the
      possible reservoirs of these pathogens in the environment and in wildlife, their
      role as sources of infection in humans and animals and their health impact on
      humans. The possibilities of control and management programmes for these
      mycobacterial infections are examined with regards to the importance of their
      natural reservoirs.

PMID- 15845233
TI  - From the recent lessons of the Malagasy foci towards a global understanding of
      the factors involved in plague reemergence.
AB  - Re-emergence of human cases of plague after decades of silence does not
      necessarily mean that plague foci are re-emerging. Most often, Yersinia pestis
      bacteria have been maintained and circulating at low levels in the rodent
      populations. It seems therefore more appropriate to speak in terms of expansion
      or regression phases for sylvatic rodent plague foci and to reserve the term re
      emergence for human cases. From the analysis of well-documented human plague
      cases in Madagascar, we underline the causes of re-emergence that can be
      generalized to most world foci, and can help define environments at risk where
      the threat of new emergence lurks. In all recent plague outbreaks, usually more
      than one risk factor was at the origin of the re-emergence. The reduction or
      discontinuance of surveillance and control, as well as poverty and insalubrity
      are the main factors in the re-emergence of human cases, allowing increased
      contacts with infected rodents and fleas. Environment changes (i.e. climatic
      changes, deforestation, urbanization) induce changes in flea and rodent
      populations by (i) extension of rodent habitats (for example by replacing forests
      by steppes or farmlands); (ii) modifications in population dynamics (possible
      outbreaks due to an increase of available food resources); but also, (iii)
      emergence of new vectors, reservoirs and new Y. pestis genotypes. Numerous and
      spontaneous genomic rearrangements occur at high frequencies in Y. pestis, which
      may confer selective advantages, enhancing the ability of Y. pestis to survive,
      to be transmitted to new hosts, and to colonize new environments. Therefore, any
      environmental change should be taken as a warning signal and active surveillance
      programs should be initiated.

PMID- 15845234
TI  - Tularemia: emergence/re-emergence.
AB  - Francisella tularensis is a gram-negative coccobacillus and the etiologic agent
      of the zoonotic disease tularemia. First described in 1911 in Tulare County,
      California, it has since been reported throughout the Northern Hemisphere, with
      natural infections reported among an unusually wide range of vertebrates and
      invertebrates. In recent years, tularemia has emerged in new geographic
      locations, populations, and settings. This review will serve to highlight
      mechanisms contributing to the recent emergence of tularemia as well as a
      repertoire of diagnostic tools useful for detecting and diagnosing disease.

PMID- 15845235
TI  - Tick- and flea-borne rickettsial emerging zoonoses.
AB  - Between 1984 and 2004, nine more species or subspecies of spotted fever
      rickettsiae were identified as emerging agents of tick-borne rickettsioses
      throughout the world. Six of these species had first been isolated from ticks and
      later found to be pathogenic to humans. The most recent example is Rickettsia
      parkeri, recognized as a human pathogen more than 60 years after its initial
      isolation from ticks. A new spotted fever rickettsia, R. felis was also found to
      be associated with fleas and to be a human pathogen. Similarly, bacteria within
      the family Anaplasmataceae have been considered to be of veterinary importance
      only, yet three species have been implicated in human diseases in recent years,
      including Ehrlichia chaffeensis, the agent of human monocytic ehrlichiosis,
      Anaplasma phagocytophilum, the agent of human anaplasmosis (formerly known as
      "human granulocytic ehrlichiosis agent", E. equi and E. phagocytophila), and
      finally Ehrlichia ewingii, which causes granulocytic ehrlichiosis in humans. We
      present here an overview of the various tick- and flea-borne rickettsial zoonoses
      described in the last 20 years, focusing on the ecological, epidemiological and
      clinical aspects.

PMID- 15845236
TI  - Important emerging bacterial zoonotic infections affecting the immunocompromised.
AB  - The immunocompromised are at particular risk for infection with zoonotic
      diseases. Persons can be temporarily immunocompromised due to pregnancy or
      developmental stage (i.e. infants); longer-term or permanent states of
      immunosuppression can occur as a result of immunosuppressive treatment following
      cancer or organ transplant, or from infectious diseases, such as AIDS. The focus
      of this review article is on emerging bacterial zoonotic diseases that are of
      particular concern among the immunocompromised. Factors that affect disease
      emergence can include factors such as human demographics and behavior; technology
      and industry; economic development and land use; international travel and
      commerce; microbial adaptation and change; and breakdown of public health
      measures. The immunocompromised need to take precautions when engaging in
      seemingly normal activities such as food preparation; caring for companion
      animals; and recreational or occupational activities. The immunocompromised are
      not only more susceptible to infection, but often suffer more serious sequelae as
      a result of infection. This review article provides an overview of the major
      foodborne, respiratory, and vector-borne bacterial pathogens that affect the
      immunocompromised. The major categories of immunodeficiency are described. In
      addition, measures that can be taken to prevent infection, including the role of
      health education, are discussed.

PMID- 15845237
TI  - Emerging or re-emerging bacterial zoonoses: factors of emergence, surveillance
      and control.
AB  - Surveillance and control of emerging bacterial zoonoses is essential in order to
      prevent both human and animal deaths and to avoid potential economic disorders
      created by trade barriers or a ban on free circulation of human or animal
      populations. An increased risk of exposition to zoonotic agents, the breakdown of
      the host's defenses, the emergence of bacterial strains resistant to antibiotics
      and their widespread distribution as well as conjunctural causes associated with
      the action or inaction of man have been identified as the main factors leading to
      the emergence or re-emergence of bacterial zoonoses. After an in-depth review of
      these various factors, the present manuscript reviews the main components of
      detection and surveillance of emerging or re-emerging bacterial zoonoses. A
      description of the systems of control and the main obstacles to their success is
      also presented. Detection and surveillance of emerging zoonoses have greatly
      benefited from technical progress in diagnostics. The success of detection and
      control of emerging bacterial zoonoses is largely based on international
      solidarity and cooperation between countries.

PMID- 15845238
TI  - Optimal size for perceiving motion decreases with contrast.
AB  - Visual patterns have widely varying contrasts and elicit local signals of varying
      reliability, ranging from noisy to relatively noise-free. One way to deal
      efficiently with the variable visual input is to employ flexible neural
      mechanisms that adapt to changing conditions. We investigated whether the spatial
      properties of motion mechanisms change with stimulus contrast and found that the
      optimal size for perceiving motion decreases with increasing contrast. These data
      were well-described by a model in which spatial summation increases with
      decreasing contrast.

PMID- 15845239
TI  - The interaction of shape- and location-based priming in object categorisation:
      evidence for a hybrid "what + where" representation stage.
AB  - The relationship between part shape and location is not well elucidated in
      current theories of object recognition. Here we investigated the role of shape
      and location of object parts on recognition, using a classification priming
      paradigm with novel 3D objects. In Experiment 1, the relative displacement of two
      parts comprising the prime gradually reduced the priming effect. In Experiment 2,
      presenting single-part primes in locations progressively different from those in
      the composite target had no effect on priming. In Experiment 3, manipulating the
      relative position of composite prime and target strongly affected priming.
      Finally, in Experiment 4 the relative displacement of single-part primes and
      composite targets did influence response time. Together, these findings are best
      interpreted in terms of a hybrid theory, according to which conjunctions of shape
      and location are explicitly represented at some stage of visual object
      processing.

PMID- 15845240
TI  - The influence of spatial and temporal noise on the detection of first-order and
      second-order orientation and motion direction.
AB  - Thresholds for identifying the direction of second-order motion (contrast
      modulated dynamic noise) are consistently higher than those for identifying
      spatial orientation, unlike first-order gratings for which the two thresholds are
      typically the same. Two explanations of this phenomenon have been proposed:
      either first-order and second-order patterns are encoded by separate mechanisms
      with different properties, or dynamic noise selectively impairs ("masks")
      sensitivity to second-order motion direction but not orientation. The former
      predicts the two thresholds should remain distinct for second-order patterns,
      irrespective of the temporal structure (static vs. dynamic) of the noise carrier.
      The latter predicts direction thresholds should be higher than orientation
      thresholds, for both second-order and first-order motion patterns, when dynamic
      (but not static) noise is present. To resolve this issue we measured direction
      and orientation thresholds for first-order (luminance) and second-order (contrast
      or polarity) modulations of static or dynamic noise. Results were decisive: The
      two thresholds were invariably the same for first-order stimuli but markedly
      different (direction thresholds approximately 50% higher) for second-order
      stimuli, regardless of the temporal properties (static or dynamic) and the
      overall contrast of the noise, or the drift temporal frequency of the envelope.
      This suggests that first-order and second-order motion are encoded separately and
      that the mechanisms encoding second-order stimuli cannot determine direction at
      the absolute threshold for spatial form.

PMID- 15845241
TI  - Characteristics of contrast processing deficits in X-linked retinoschisis.
AB  - Contrast sensitivity and contrast discrimination were evaluated in six males with
      X-linked retinoschisis (XLRS), a form of early-onset macular degeneration, using
      testing paradigms designed to favor either the magnocellular (MC) or
      parvocellular (PC) pathway. Compared to a group of age-similar control observers,
      the patients with XLRS showed a pronounced loss of contrast sensitivity at high
      spatial frequencies, consistent with their reduced visual acuities. At low
      spatial frequencies, the patients' deficits were greater under conditions
      favoring the MC pathway, for both contrast sensitivity and contrast
      discrimination. The pattern of contrast sensitivity loss shown by the patients
      with XLRS could be simulated in control observers by testing at a parafoveal
      locus, although by optical coherence tomography, none of the patients with XLRS
      had eccentric fixation. The pattern of findings indicates that the foveas of
      patients with XLRS functionally resemble the normal parafoveal retina.

PMID- 15845242
TI  - Stimulus contrast and the Reichardt detector.
AB  - The direction of a drifting grating can become more easily identified when a
      stationary, flickering grating, with the same spatial and temporal frequencies,
      is added to it. This amplification has been accepted as evidence that motion
      perception depends on the product of visual signals elicited before and after a
      target changes position, as computed by a Reichardt detector. However,
      amplification is also consistent with a model in which direction identification
      depends on the product of detection probabilities before and after the position
      shift. In this paper, we compare the Reichardt detector with a model of
      Probability Multiplication. For 2-frame sequences, similar results are predicted
      by Probability Multiplication and a Reichardt model, in which the performance
      limiting noise is early (i.e. it is added prior to signal multiplication). Many
      new and previously published results are consistent with these predictions. Other
      results are documented in which the amplification is too large to be consistent
      with Probability Multiplication. To explain these latter results, Reichardt
      detectors must have both early and late noises.

PMID- 15845243
TI  - Matching rod percepts with cone stimuli.
AB  - Traditional methods for studying the effects of rod activity on color vision make
      it hard to assess the underlying physiological mechanisms. In this study, rod
      mediated changes in color appearance were assessed by matching them with cone
      mediated color changes. A four-primary photostimulator allowed independent
      control of rod and cone stimulation and identification of the cone types that
      generate color sensations equivalent to rod color sensations. The results showed
      that increases in rod stimulation required matches with cone stimuli that excited
      M-cones more than L-cones for all conditions. Matches for low-luminance
      conditions also required some S-cone stimulation. A subsidiary experiment showed
      that increases in rod modulation of an inducing field produced chromatic contrast
      effects like those produced by the M-cone system. The data are consistent with a
      hypothesis of perceptual normalization of scotopic vision to the chromatic
      appearance of objects under photopic conditions.

PMID- 15845244
TI  - Discrimination of speed in 5-year-olds and adults: are children up to speed?
AB  - We compared thresholds for discriminating changes in speed by 5-year-olds and
      adults for two reference speeds: 1.5 and 6 degrees s(-1). Both adults and 5-year
      olds were more sensitive to changes from the faster than from the slower
      reference speed. Five-year-olds were less sensitive than adults at both reference
      speeds but significantly more immature at the slower (1.5 degrees s(-1)) than at
      the faster (6 degrees s(-1)) reference speed. The findings suggest that the
      mechanisms underlying speed discrimination are immature in 5-year-olds,
      especially those that process slower speeds.

PMID- 15845245
TI  - Pattern specificity of human visual motion processing.
AB  - Visual motion processing is strongly susceptible to adaptation. A variety of
      patterns have been used as stimuli in previous studies. Three of these, namely
      random dots, barcode-like gratings, and sinusoidal gratings, were compared in the
      present study using motion-onset visual evoked potentials (VEPs). We assessed the
      effects of the adaptation pattern and the test pattern to which the VEP is
      recorded. Furthermore, we evaluated the interaction between both, i.e. whether
      differences between adaptation and test pattern affect the response.
      Isodirectional and antidirectional adaptation were used to differentiate between
      the actual motion adaptation and associated flicker adaptation. Motion adaptation
      was almost 2.5-fold stronger (p < 0.01) if the same rather than different pattern
      types were used for both adaptation and test. This implies that separate neural
      populations are involved, suggesting the presence of pattern-tuned motion
      mechanisms.

PMID- 15845246
TI  - Detection of symmetry and anti-symmetry.
AB  - To assess the role of second-order channels in symmetry perception we measured
      the effects of check size, spatial frequency content, eccentricity and grey scale
      range on the detection of symmetrical and anti-symmetrical patterns. Thresholds
      for symmetrical stimuli were only moderately affected by these manipulations.
      Anti-symmetrical stimuli composed of large black and white checks elicited low
      thresholds. However, anti-symmetry became essentially undetectable at small check
      sizes. Removing low frequencies from large-check-size, anti-symmetrical stimuli
      had little effect on thresholds whereas removing high frequencies had a
      pronounced effect. Moving the stimuli from fixation to 8 degrees eccentricity
      caused a dramatic increase in thresholds for anti-symmetrical stimuli but not
      symmetrical stimuli. When the grey scale range was increased anti-symmetry was
      undetectable at any check size whereas symmetry was easily seen at all. We argue
      that these results and others in the literature suggest that anti-symmetry is
      only detected under conditions favourable to selective attention.

PMID- 15845247
TI  - Saliency and context play a role in infants' texture segmentation.
AB  - We investigated whether young infants orient reliably towards more salient vs.
      less salient objects in a visual scene. Subjects were tested with stimuli
      presented on textured fields, one side showing a target stimulus (a 'more
      salient' or 'less salient' texture patch) and the other a background stimulus.
      Infants typically preferred the more salient, but not the less salient target.
      Their behaviour depended on the configuration of the background stimulus. In
      contrast, 3-4 year-old children always showed a preference for the target
      stimulus, regardless of the configuration of the background. We conclude that
      both saliency of a target stimulus and its context play a role in early texture
      segmentation.

PMID- 15845248
TI  - Systematic distortions of perceptual stability investigated using immersive
      virtual reality.
AB  - Using an immersive virtual reality system, we measured the ability of observers
      to detect the rotation of an object when its movement was yoked to the observer's
      own translation. Most subjects had a large bias such that a static object
      appeared to rotate away from them as they moved. Thresholds for detecting target
      rotation were similar to those for an equivalent speed discrimination task
      carried out by static observers, suggesting that visual discrimination is the
      predominant limiting factor in detecting target rotation. Adding a stable visual
      reference frame almost eliminated the bias. Varying the viewing distance of the
      target had little effect, consistent with observers underestimating distance
      walked. However, accuracy of walking to a briefly presented visual target was
      high and not consistent with an underestimation of distance walked. We discuss
      implications for theories of a task-independent representation of visual space.

PMID- 15845249
TI  - Attenuation of perceived motion smear during the vestibulo-ocular reflex.
AB  - Previous studies indicated that less motion smear is perceived when a physically
      stationary target is presented during voluntary eye movements than when similar
      retinal-image motion occurs during steady fixation. In this study, we assessed
      whether the perception of motion smear is attenuated also during the involuntary
      vestibulo-ocular reflex (VOR). Normal observers matched the length of perceived
      smear in two experimental conditions that were designed to produce similar
      trajectories of retinal image motion. In the fixation condition, a small bright
      target was presented for a duration of 50-200 ms in rightward or leftward motion,
      while the observer remained stationary and maintained fixation. In the VOR
      condition, the target moved along with the observer, who underwent full-body
      rotation around a vertical axis in darkness. Horizontal eye movement recordings
      during VOR trials allowed us to calculate the velocity of retinal image motion on
      each VOR trial. The principal result was that the extent of perceived motion
      smear was significantly less during VOR than fixation trials, particularly for
      target durations of 100 ms or longer. These findings support the conclusion that
      extra-retinal signals during the involuntary VOR contribute to a reduction of
      perceived motion smear.

PMID- 15845250
TI  - Bacterial viruses against viruses pathogenic for man?
AB  - In this review, we discuss possible models of bacteriophage-virus interactions.
      The first is based on the mechanism by which phages may interact indirectly with
      viruses. Its essence is that bacteriophage-derived nucleic acid may inhibit
      pathogenic virus infection. It seems that this phenomenon can be partly explained
      on the basis of interferon induction. We also discuss a study by Borecky's group
      (conducted over two decades ago) which provided some clinical data on the
      effectiveness of the application of native bacteriophage RNA in the treatment of
      viral infections. The second interaction model is based on the direct competition
      of bacteriophages and viruses for cellular receptors for viral cell-entry. The
      use of bacteriophages as inducers or displayers of antibodies with antiviral
      action is considered as the third model. In this part of the article, we also
      discuss other data and hypotheses on conceivable interactions between bacterial
      and animal viruses. As our current supply of antiviral drugs is quite limited,
      using natural agents such as bacteriophages as a weapon against pathogenic
      viruses could be an attractive and cost-efficient alternative, and further
      studies are urgently needed to test this possibility.

PMID- 15845251
TI  - Fitness and virulence of an ancestral White Spot Syndrome Virus isolate from
      shrimp.
AB  - White Spot Syndrome Virus, the type species of the virus family Nimaviridae, is a
      large dsDNA virus infecting shrimp and other crustaceans. Genomic analysis of
      three completely sequenced WSSV isolates identified two major polymorphic loci,
      "variable region ORF14/15" and "variable region ORF23/24". Here, we characterize
      a WSSV isolate originating from shrimp collected in Thailand in 1996 (TH-96-II).
      This isolate contains the largest WSSV genome ( approximately 312 kb) identified
      so far, mainly because of its sequences in both major polymorphic loci. Analysis
      of "variable region ORF14/15" suggests that TH-96-II may be ancestral to the WSSV
      isolates described to date. A comparison for virulence was made between TH-96-II
      and WSSV-TH, a well characterized isolate containing the smallest genome (
      approximately 293 kb) identified at present. After injection of the isolates into
      Penaeus monodon the mortality rates showed that the median lethal time (LT50) of
      TH-96-II was approximately 14 days, compared to 3.5 days for WSSV-TH. When both
      isolates were mixed in equal amounts and serially passaged in shrimp, WSSV-TH
      outcompeted TH-96-II within four passages. These data suggest a higher virulence
      of WSSV-TH compared to TH-96-II. The molecular basis for the difference in
      virulence remains unclear, but a replication advantage of the 19 kb smaller WSSV
      TH genome could play a role.

PMID- 15845252
TI  - Identification and function of a shrimp white spot syndrome virus (WSSV) gene
      that encodes a dUTPase.
AB  - The ORF wsv112 of shrimp white spot syndrome virus (WSSV) was predicted to encode
      a protein with five conserved motifs at its N-terminus characteristics of
      dUTPases. The transcription of the gene named as wdut was analyzed by RT-PCR and
      RACE. The C-terminal end of the putative WSSV dUTPase bore very low similarity to
      the reported dUTPases and any other known proteins. Therefore, the 5'-terminal
      region (528-bp) of wdut gene was expressed in E. coli. The recombinant WSSV
      dUTPase (WDUT) with a molecular mass of 23 kDa could catalyze the hydrolysis of
      dUTP into dUMP and was highly specific for dUTP with an apparent Km of 1.2
      microM. Furthermore, gel filtration results revealed that this enzyme was a
      trimer.

PMID- 15845253
TI  - Three unrelated viruses occur in a single isolate of Gremmeniella abietina var.
      abietina type A.
AB  - Five enclosed double-stranded RNA (dsRNA) bands in electrophoresis, probably of
      viral origin, were found from a single isolate (SurS4) of Gremmeniella abietina
      var. abietina type A. Analysis of the dsRNAs revealed that they represented three
      different viruses, named as Gremmeniella abietina mitochondrial RNA virus S2
      (GaMRV-S2), Gremmeniella abietina RNA virus MS2 (GaRV-MS2) and Gremmeniella
      abietina RNA virus L2 (GaRV-L2). The genome of GaMRV-S2 was 2587 base pairs (bp)
      long and had a very low GC content (31%). Sequence variations occurred at both
      ends. The genome coded for a putative RNA-dependent RNA polymerase (RdRp) under a
      mitochondrial translation code. The GaRV-MS2 genome was composed of three dsRNA
      molecules (1781 bp, 1586 bp and 1186 bp). They coded for a putative RdRp, a coat
      protein (CP) and a protein with an unknown function, respectively. The GaRV-L2
      genome was 5129 bp long and contained two ORFs. The 5'-proximal ORF coded for a
      putative CP, whereas the 3'-proximal ORF encoded for a putative RdRp. The buoyant
      density of GaRV-MS2 and GaRV-L2 were 1.37 and 1.42 g/ml, respectively. GaMRV-S2,
      GaRV-MS2 and GaRV-L2 were closely related to the previously described viruses
      GaMRV-S1, GaRV-MS1 and GaRV-L1, respectively, and are putative members of the
      genera Mitovirus, Partitivirus and Totivirus, respectively. This is the first
      report on the occurrence of viruses of all these different genera in a single
      fungal isolate.

PMID- 15845254
TI  - Transcriptional analysis of avian embryonic tissues following infection with
      avian infectious bronchitis virus.
AB  - Avian infectious bronchitis virus (IBV) infection is one of the major viral
      respiratory diseases of chickens. Better understanding of the molecular basis of
      viral pathogenesis should contribute significantly towards the development of
      improved prophylactic, therapeutic and diagnostic reagents to control infections.
      In the present investigation, transcriptional profiles were analyzed by using RNA
      recovered from the lung tissue of IBV infected 18-day-old chicken embryos at 6,
      24, 48 and 72 h post IBV infection. This microarray analysis was completed using
      avian cDNA arrays comprised of fragments of 1191 unique chicken and turkey gene
      transcripts. These arrays were generated from normalized cDNA subtraction
      libraries that were derived from avian pneumovirus (APV) infected chicken embryo
      fibroblast (CEF) cultures and tissues obtained from APV infected turkeys
      subtracted with their respective uninfected cultures and tissues. Of the 1191
      unique genes represented on the array, the expression of a total of 327 genes
      (27% of total) were altered by two-fold or more from 6 through 72 h post
      infection. A comparative analysis of IBV regulated genes with genes previously
      reported to change in expression following infection with other avian respiratory
      viruses revealed both conserved and unique changes. Real-time qRT-PCR was used to
      confirm the regulated expression of genes related to several functional classes
      including kinases, interferon induced genes, chemokines and adhesion molecules,
      vesicular trafficking and fusion protein genes, extracellular matrix protein
      genes, cell cycle, metabolism, cell physiology and development, translation, RNA
      binding, lysosomal, protein degradation and ubiquitination related genes.
      Microarray analysis served as an efficient tool in facilitating a comparative
      analysis of avian respiratory viral infections and provided insight into host
      transcriptional changes that were conserved as well as those which were unique to
      individual pathogens.

PMID- 15845255
TI  - Co-purification of soluble membrane cofactor protein (CD46) and human herpesvirus
      6 variant A genome in serum from multiple sclerosis patients.
AB  - The association of human herpesvirus 6 (HHV-6) and multiple sclerosis (MS) has
      been supported by several immunological and molecular studies. Recently, membrane
      cofactor protein (CD46) has been identified as the cellular receptor for the A
      and B variants of HHV-6. Elevated levels of soluble CD46 (sCD46) have been
      reported in the serum and CSF of MS patients. The aim of this study was to
      investigate a possible correlation between elevated levels of soluble CD46 and
      the presence of serum HHV-6 DNA in MS patients. An immunoaffinity column
      comprised of immobilized monoclonal antibodies to CD46 was developed to isolate
      sCD46 from cell free body fluids of MS patients and controls. After
      immunoaffinity purification, DNA was extracted from anti-CD46 column eluates and
      subjected to PCR amplification. Of the 42 MS samples tested, 4 serum samples were
      HHV-6 positive, 3 of which were typed as HHV-6A. The co-purification of sCD46 and
      HHV-6 DNA from MS sera indicates that HHV-6 is tightly connected to its receptor,
      CD46, in the serum of MS patients.

PMID- 15845256
TI  - Phenotypic and molecular characterization of a non-lethal, hamster-viscerotropic
      strain of yellow fever virus.
AB  - Viscerotropic yellow fever virus (YFV) infection occurs primarily in humans and
      non-human primates. Lack of an appropriate small animal model of viscerotropic
      YFV infection has been a major deterrent to molecular studies of viscerotropism.
      A hamster model of viscerotropic YFV infection has recently been described;
      however, these studies have focused on hamster-viscerotropic strains of YFV
      (including Asibi hamster P7 virus) that caused outward clinical signs of
      infection and mortality. In order to map more closely the molecular determinants
      of viscerotropism in the hamster model, a second sequential series of seven liver
      to-liver passages of Asibi virus was undertaken through hamsters to generate
      Asibi P7b virus. Asibi hamster P7b virus did not cause clinically detectable
      signs of YFV infection; however, high quantities of circulating virus were
      isolated from the serum, and microscopic evaluation of the liver and spleen
      demonstrated histopathological lesions consistent with YFV infection. The genomic
      sequence of Asibi P7b virus was determined and compared to wild-type Asibi virus
      and the lethal, hamster-viscerotropic Asibi P7 virus and found to differ by only
      two amino acids in the envelope protein, E-98 and E-331.

PMID- 15845257
TI  - Characterization of gp41 gene of Spodoptera litura multicapsid
      nucleopolyhedrovirus.
AB  - Spodoptera litura multicapsid nucleopolyhedrovirus (SpltMNPV) gp41 gene is 993 bp
      long and the protein encoded by this gene has 6-66% amino acid identities with
      other known baculovirus GP41 proteins. Slgp41 transcripts were detected from 12
      to 96 h post-infection (p.i.) and the mRNA start site was mapped within a
      consensus baculovirus late promoter sequence (ATAAG). Western blot analysis of
      extracts from SpltMNPV-infected S. litura cells detected a 41 kDa protein, and
      this protein was present in the nucleus of infected cells from 12 to 96 h p.i.,
      whereas in the cytoplasm from 24 to 96 h p.i. Structural localization confirmed
      that SlGP41 is associated with the envelope of occlusion-derived virus (ODV).
      Lectin-binding assay showed that three lectins erythrina cristaglli lectin (ECL),
      lycopersicon esculentum lectin (LEL), and bandeiraea simlicifolia lectin (BSL)
      recognizing N-acetylglucosamine were specifically bound to SlGP41. It was
      proposed that SlGP41 is an O-glycoprotein.

PMID- 15845258
TI  - A human papillomavirus type 16 vaccine by oral delivery of L1 protein.
AB  - To establish an edible HPV16 vaccine, we constructed a recombinant HPV16 L1
      expressing Schizosaccharomyces pombe yeast strain (HPV16L1 yeast). A preliminary
      study revealed that freeze-dried yeast cells could be delivered safely, and were
      digested in the mouse intestine. The freeze-dried HPV16 L1 yeast was administered
      orally as an edible vaccine, with or without the mucosal adjuvant heat-labile
      toxin LT (R192G), to 18 female BALB/c mice. After the third immunization, none of
      the mice that received the edible HPV16 vaccine showed specific antibody
      responses, whereas all of the positive controls that were administered
      intranasally with 5 microg of HPV16-virus-like particles (VLP) had serum IgG, and
      genital IgA and IgG that reacted with HPV16-VLP in enzyme-linked immunosorbent
      assays (ELISAs). When a suboptimal dose (1 microg) of HPV16-VLP was administered
      to all the mice, including the negative control mice, 50% of the mice that were
      pre-immunized with the edible HPV16 vaccine showed positive serum IgG responses,
      while none of the negative controls showed any response. Vaginal IgG and IgA
      antibodies were also elicited in 33 and 39%, respectively, of the mice that were
      given with the edible HPV16 vaccine and the intranasal boost. All of the
      antibodies reacted more strongly to intact HPV16-VLP than to denatured HPV16-L1
      protein suggesting that the edible vaccine primes for antibody responses against
      conformation-dependent epitopes. The inclusion of adjuvant in the vaccine
      formulation marginally increased the genital IgA response (P=0.06). HPV16-L1
      protein in the yeast might induce tolerance in the vaccinated animals that could
      be recovered by intranasal boosting with a suboptimal dose of HPV-VLP. This
      freeze-dried yeast system may be useful as an oral delivery of HPV 16 L1 protein.

PMID- 15845259
TI  - Characterization of the norovirus 3C-like protease.
AB  - The recombinant 3C-like protease of Chiba virus, a Norovirus, expressed in
      Escherichia coli cells was purified and characterized as to effects of pH,
      temperature, salt contents, and SH reagents on its proteolytic activity. The
      optimal pH and temperature of the 3C-like protease for the proteolytic activity
      were 8.6 and 37 degrees C, respectively. Increased concentration (approximately
      100 mM) of monovalent cations such as Na+ and K+ was inhibitory to the activity.
      Hg2+ and Zn2+ remarkably inhibited the protease activity, while Mg2+ and Ca2+ had
      no virtual effect. Several sulfhydryl reagents such as p-chloromercuribenzoic
      acid, methyl methanethiosulfonate, N-ethylmaleimide and N-phenylmaleimide also
      blocked the activity, confirming the previous result that cysteine residue(s)
      were responsible for the proteolysis.

PMID- 15845260
TI  - Nucleotide sequence and phylogenetic analyses of the DNA polymerase gene of
      Anticarsia gemmatalis nucleopolyhedrovirus.
AB  - The DNA polymerase from Anticarsia gemmatalis nucleopolyhedrovirus (AgMNPV) was
      identified and sequenced, and its amino acid sequence was compared with other
      viral DNA polymerases to identify conserved regions and to reconstruct a
      phylogenetic tree. The sequence analysis of the AgMNPV DNA polymerase gene
      revealed the presence of a 2976 nucleotides open reading frame (ORF) encoding a
      polypeptide of 991 amino acid residues with a predicted molecular mass of 114.7
      kDa. Among the baculovirus DNA polymerase genes identified to date, the AgMNPV
      DNA polymerase gene shared maximum amino acid sequence identity with the DNA
      polymerase gene of Choristoneura fumiferana nucleopolyhedrovirus defective strain
      (CfDEFNPV) (94%). The alignment of 140 virus sequences, 23 of them from
      baculovirus, showed that, of the 10 conserved regions identified, 5 are exclusive
      to baculoviruses (R1, R5, R9, R6 and R10), only 2 of them (R6 and R10) previously
      described as such in the literature. Our analysis, based on their positions in
      the AgMNPV DNA polymerase model, suggests that R9 and R10 could interact with
      DNA. Phylogenetic analysis of DNA polymerase sequences places the enzyme from
      AgMNPV within the cluster containing the polymerases of Group I
      Nucleopolyhedrovirus and suggests that the AgMNPV DNA polymerase is more closely
      related to that of CfDEFNPV than to those of other baculoviruses.

PMID- 15845262
TI  - Full genome sequence of peste des petits ruminants virus, a member of the
      Morbillivirus genus.
AB  - Peste des petits ruminants virus (PPRV) causes an acute febrile illness in small
      ruminant species, mostly sheep and goats. PPRV is a member of the Morbillivirus
      genus which includes measles, rinderpest (cattle plague), canine distemper,
      phocine distemper and the morbilliviruses found in whales, porpoises and
      dolphins. Full length genome sequences for these morbilliviruses are available
      and reverse genetic rescue systems have been developed for the viruses of
      terrestrial mammals, with the exception of PPRV. This paper presents the first
      published full length genome sequence for PPRV. The genome was found to be
      consistent with the rule-of-six and open reading frames (ORFs) were identified
      that encoded the eight proteins characteristic of morbilliviruses. At the
      nucleotide (nt) level, the full length genome of PPRV was most similar to that of
      rinderpest, the other ruminant morbillivirus. However, at the protein level five
      of the six structural proteins and the V protein showed a greater similarity to
      the dolphin morbillivirus (DMV) while only the C and L proteins showed a high
      relationship to rinderpest.

PMID- 15845261
TI  - Phylogenetic analysis of classical swine fever virus (CSFV) field isolates from
      outbreaks in South and Central America.
AB  - To date, there is little information concerning the epidemiological situation of
      classical swine fever (CSF) in the Americas. Besides summarizing the available
      data, genotyping of isolates from outbreaks in domestic pigs in several countries
      of South and Central America was performed. For this, a 190 base fragment of the
      E2 envelope glycoprotein gene was used. European strains and isolates, and
      historical isolates from the United States (US) were included for comparison. In
      contrast to the situation in most parts of Europe, where group 2 isolates
      predominate, it was found that all the isolates from the American continent
      analyzed belonged to group 1 and were further resolved into three subgroups. The
      Cuban isolates clustered in subgroup 1.2, whereas the isolates from Honduras and
      Guatemala clustered in subgroup 1.3. The remaining isolates from Argentina,
      Brazil, Colombia and Mexico generated four poorly resolved clusters in subgroup
      1.1, together with the vaccine strains, with historical European and US isolates,
      and with a recent Russian isolate. While the vaccine strains and the historical
      European isolates formed a relatively distinct cluster, one of the US isolates
      clustered together with the Mexican, and another one with Colombian isolates.
      Historically, CSF (hog cholera) was observed almost simultaneously in the US and
      in Europe in the first half of the 19th century, and its origin remains a matter
      of discussion. Our results showed that the US isolates are closely related to
      isolates from South America, while appearance of isolates in Cuba on one hand and
      in Honduras and Guatemala on the other hand, seems to have been due to unrelated
      events. This allows to speculate that at least in the American continent, CSF
      virus may have appeared independently in several regions, and spreading may have
      been a secondary effect.

PMID- 15845263
TI  - Tomato spotted wilt virus S-segment mRNAs have overlapping 3'-ends containing a
      predicted stem-loop structure and conserved sequence motif.
AB  - The Tomato spotted wilt virus ambisense M- and S-RNA segments contain an A/U-rich
      intergenic region predicted to form a stable hairpin structure. The site of
      transcription termination of S-segment encoded N and NSs mRNAs synthesised in an
      in vitro transcription system was roughly mapped to the 3'-end of the intergenic
      hairpin, i.e. position 1568-1574 for N and position 1852-1839 for NSs, as
      determined by RT-PCR cloning and size estimation on Northern blots. This suggests
      that these viral transcripts contain a predicted stem-loop structure at their 3'
      end. The potential involvement of the 3'-end structure in transcription
      termination is discussed.

PMID- 15845264
TI  - Protein expression in white spot syndrome virus infected Penaeus monodon
      fabricius.
AB  - White spot syndrome virus (WSSV) is the causative agent of the white spot disease
      of shrimp. Penaeus monodon were captured from Muttukadu Estuary in Chennai,
      India, transported to the laboratory and maintained in an aerated system with
      continuous water circulation-biofiltration. WSSV-free P. monodon were challenged
      by feeding them only once with WSSV-infected tissues of P. monodon. Cumulative
      mortality (100%) of the infected individuals was determined. Tissues from
      infected and uninfected shrimp such as muscles, hepatopancreas, heart, gills and
      eye tissues (100mg of each) and haemolymph (50 microl) were subjected to SDS
      PAGE. In infected muscle tissue, six newly expressed proteins were detected. In
      infected haemolymph, four new proteins and three intensely expressed high
      molecular weight proteins were observed. Three intensely expressed high molecular
      weight proteins were detected in infected heart tissue and two new proteins in
      infected hepatopancreatic tissues. In infected gill tissues, two new protein
      bands and three intensely expressed high molecular weight proteins were detected
      on comparison with uninfected tissues. Similarly, two intensely expressed protein
      bands were seen in the infected as compared with the uninfected eye tissues. The
      protein profiles of the muscle tissue from 50 different naturally infected (WSSV)
      shrimp were analyzed. Eleven different new protein bands appeared in the infected
      muscle tissues when compared to the control muscle tissues whereas; in muscle
      tissue six new proteins were observed both in naturally and experimentally WSSV
      infected shrimp. The current study has shown that the protein expression patterns
      of the infected tissues of P. monodon have been drastically altered by WSSV
      infection. Western blot analysis revealed that one of the newly expressed 53 kDa
      protein in the infected muscle represents the WSSV envelope protein.

PMID- 15845265
TI  - Nucleotide sequence analysis of Plum pox virus isolate W3174: evidence of a new
      strain.
AB  - The nucleotide sequence of Plum pox virus (PPV) isolate W3174 was determined. The
      virus genome consists of 9788 nucleotides (nt), excluding the poly(A) tail at the
      3'-terminus, with 5'- and 3'-untranslated regions (UTRs) of 146 and 219 nt,
      respectively. The deduced polyprotein consists of 3141 amino acid (aa) residues,
      with the coat protein region consisting of 993 nt (331 aa). In comparisons with
      PPV-D, -M, -EA and -C isolates, nucleotide identity levels ranged from 79 to 80%
      for the entire genome and from 78 to 79%, 78 to 81%, and 92 to 95% for the NIb,
      CP, and 3'-UTR regions, respectively. The majority of nucleotide substitutions in
      the NIb region of W3174 are silent, while substitutions in the CP region are not
      silent, giving aa identities of 89-91% and 79-81%, respectively. The HC-Pro
      region contains the KITC and PTK motifs, and the DAG motif is located at
      positions 12-14 of the deduced CP aa sequence, all associated with aphid
      transmission. Phylogenetic analysis based on the complete genome sequence, the
      NIb, CP, and 3'-UTR region were performed. PPV-W3174 consistently formed a
      distinct clade or group, when compared to members of all four recognized strains
      of PPV, indicating that it is genetically distinct. These results are consistent
      with serological and nucleic acid-based strain typing data and justify
      recognition of this isolate as representative of a new strain identified as PPV
      W.

PMID- 15845266
TI  - Molecular characterization of the rotavirus NSP4 enterotoxin homologue from group
      B rotavirus.
AB  - The RNA segment (Gene 10) from a human group B rotavirus which encodes the
      homologue of the rotavirus enterotoxin (NSP4) has been cloned and sequenced. The
      gene is of the same length (751 nucleotides) as its better-characterized group A
      rotavirus counterpart but shows minimal homology (approximately 10%) to it at the
      primary sequence level. Despite this low level of sequence homology, secondary
      structure predictions for the group B protein (ADRV-NSP4) showed a close
      similarity of structural features with the group A protein. Full-length ADRV-NSP4
      was expressed in Escherichia coli with an amino terminal 6xHis tag that was used
      to purify it to homogeneity. The cytotoxicity of the purified protein was
      examined in a rapid dye-uptake assay that assesses membrane permeability and was
      found to be comparable to its group A counterpart.

PMID- 15845267
TI  - Molecular analysis of quasispecies of Kyuri green mottle mosaic virus.
AB  - The population diversity of progeny viruses of Kyuri green mottle mosaic virus
      (KGMMV) in consecutive serial passages in two systemic hosts, zucchini squash and
      cucumber plants, established from genetically identical viral RNA, was examined
      in this study. An initial plant was inoculated with in vitro transcripts from a
      full-length cDNA clone of KGMMV. The initial viral population (passage 0) was
      transferred five times in parallel populations in the same hosts species for
      analysis of progenies of KGMMV. The percentage of mutations of progeny viruses
      fluctuated slightly, as expected, during the serial passage, and these results
      did not correlated with the mutation frequency calculated as the total number of
      mutation observed in all the clones sequenced for a given viral population were
      divided by the total number of bases sequenced for the population. The mutation
      frequencies represented similar distributions over the course of serial passages
      in the two systemic host plants. Seventeen unique mutations were detected from a
      total of 40 clones (19,120 bases) sequenced, indicating a relatively small
      overall mutation rate of 17 nucleotide substitutions. The majority of observed
      mutations in the viral populations consisted of substitutions: 61.60 and 64.08%
      of the mutations in cucumber and zucchini populations, respectively. The types of
      transitions and silent mutations indicated that progenies of KGMMV reached
      stabilized selection during the host passages and maintained viral quasispecies
      in systemic hosts.

PMID- 15845268
TI  - Evaluation of promoters for foreign gene expression in the E3 region of bovine
      adenovirus type-3.
AB  - In order to optimize foreign gene expression in the E3 region of BAdV-3, we
      constructed full-length BAdV-3 genomic DNA clones containing a reporter gene
      (truncated glycoprotein gD of bovine herpesvirus 1, gDt), under the control of
      exogenous promoters inserted in either direction in the E3 region. Irrespective
      of exogenous transcriptional elements, viable recombinant BAdV-3 viruses could
      only be isolated when the gDt expression cassettes were inserted in the E3 region
      parallel to the direction of E3 transcription. Introduction of exogenous
      promoters altered the kinetics and amount of gDt expression in recombinant BAdV-3
      infected cells. Interestingly, recombinant BAdV-3 containing gDt under the
      control of the mouse cytomegalovirus (MCMV) immediate early (IE) promoter
      expressed gDt more efficiently with noticeable differences in the amount and
      kinetics of expression. Moreover, animals immunized with recombinant BAdV-3
      expressing gDt under the control of the MCMV IE promoter induced strong immune
      responses with reduced pathological lesions. These results suggest that BAdV
      vectors with the MCMV IE promoter may be useful for transgene expression and the
      development of vaccines.

PMID- 15845269
TI  - A single amino acid residue of RNA-dependent RNA polymerase in the Potato virus X
      genome determines the symptoms in Nicotiana plants.
AB  - A Potato virus X (PVX) strain, PVX-OS, causes a necrotic mosaic in Nicotiana
      benthamiana and ring spot mosaic in N. tabacum cv. SamsunNN. By contrast, strain
      PVX-BS causes a mild mosaic in N. benthamiana and systemic asymptomatic infection
      in N. tabacum cv. SamsunNN. To investigate the viral determinant of this
      difference, we produced various infectious cDNA clones chimeric between these PVX
      genomes and clones with point mutations introduced by site-directed mutagenesis.
      Inoculation tests with these clones mapped the symptom determinant in Nicotiana
      plants to the 1422 amino acid residue in the region of the C-terminus of RNA
      dependent RNA polymerase (RdRp). Western blot analysis and local lesion assay
      indicated that virus accumulation in the infected leaves was similar for these
      PVX strains, suggesting that the symptom difference was not due to virus
      accumulation.

PMID- 15845270
TI  - Tomato spotted wilt virus glycoprotein G(C) is cleaved at acidic pH.
AB  - Tomato spotted wilt virus (TSWV) is a plant-infecting member of the family
      Bunyaviridae. TSWV encodes two envelope glycoproteins, G(N) and G(C), which are
      required for virus infection of the arthropod vector. Other members of the
      Bunyaviridae enter host cells by pH-dependent endocytosis. During this process,
      the glycoproteins are exposed to conditions of acidic pH within endocytic
      vesicles causing the G(C) protein to change conformation. This conformational
      change renders G(C) more sensitive to protease cleavage. We subjected TSWV
      virions to varying pH conditions and determined that TSWV G(C), but not G(N), was
      cleaved under acidic pH conditions, and that this phenomenon did not occur at
      neutral or alkaline pH. This data provides evidence that G(C) changes
      conformation at low pH which results in altered protease sensitivity.
      Furthermore, sequence analysis of G(C) predicts the presence of internal
      hydrophobic domains, regions that are characteristic of fusion proteins. Like
      studies with other members of the Bunyaviridae, this study is the first step
      towards characterizing the nature of cell entry by TSWV.

PMID- 15845271
TI  - Cellular uptake of the EBV transcription factor EB1/Zta.
AB  - A number of viral proteins have the property to penetrate into the cells when
      present in the extra-cellular compartment. Here, we report that the Epstein-Barr
      virus (EBV) transcriptional activator EB1/Zta, which is responsible for the
      activation of the EBV lytic replication, binds to lymphoid cells surface, is
      efficiently translocated and accumulates in the nucleus. The internalization of
      EB1/Zta is energy-dependent and shares common features with endocytosis. As the
      EB1/Zta was not degraded in the cells and reached the nucleus, the potential
      effect of its internalisation on viral reactivation was assessed.

PMID- 15845272
TI  - Responses of chickens vaccinated with a live attenuated multi-valent ionophore
      tolerant Eimeria vaccine.
AB  - Coccidiosis, caused by Eimeria species, is a serious economic disease of chickens
      (Gallus gallus) and the search for vaccines to control the disease is
      intensifying especially with the increasing threat of drug resistance. A live
      attenuated multi-valent ionophore-tolerant Eimeria vaccine has been developed
      that contains three ionophore-resistant Eimeria species, E. tenella, E. maxima
      and E. acervulina. The attenuated lines were derived from virulent field strains
      resistant to monensin ionophore by selection for early development in chicks. The
      vaccine was administered by gavage and through drinking water to broiler
      chickens, Chinese Yellow strain, reared in wire cages. Vaccinated medicated birds
      performed better than vaccinated unmedicated and medicated unvaccinated groups.
      The final mean weights of vaccinated medicated birds were significantly higher
      (P<0.05), and a better vaccine protection index, using both vaccinating methods,
      was achieved. Results indicated that concomitant use of ionophores and vaccines
      could be a useful adjunct to planned immunization in the control of coccidiosis.

PMID- 15845273
TI  - Seroepidemiology of leptospirosis, toxoplasmosis, and leishmaniosis among dogs in
      Ankara, Turkey.
AB  - Seroprevalence of five different Leptospira interrogans serovars, Toxoplasma
      gondii and Leishmania infantum in stray dogs in Ankara was investigated. A total
      of 116 dog sera collected from apparently healthy stray dogs were tested for L.
      interrogans serovars by microscopic agglutination test (MAT), for T. gondii
      antibodies by Sabin-Feldman dye test (SFDT), and for L. infantum antibodies by
      indirect fluorescence antibody test (IFAT). Of the 116 dogs, 51 (43.96%) were
      seropositive for leptospirosis, 72 (62.06%) for T. gondii and 3 (2.58%) for L.
      infantum. No statistically significant difference was observed between male and
      female dogs in the seroprevalences of toxoplasmosis and leptospirosis (P>0.05),
      but statistically significant difference was observed among different age groups
      in the seroprevalences of toxoplasmosis and leptospirosis (P<0.05). Although the
      seroprevalence of L. infantum was low, asymptomatic animals should be considered
      as a reservoir for the spread of the disease.

PMID- 15845274
TI  - The efficacy of a mixture of trimethoprim and sulphaquinoxaline against
      Plasmodium gallinaceum malaria in the domesticated fowl Gallus gallus.
AB  - The apicomplexan parasite Plasmodium gallinaceum has not been much studied from
      the veterinary standpoint. Although it causes malaria in domesticated chickens,
      no effective drugs appear to be commercially available. A mixture of trimethoprim
      and sulphaquinoxaline (TMP/SQX, ratio 1:3), with a wide spectrum of activity
      against bacteria and coccidia, is here shown to be also efficacious against blood
      induced P. gallinaceum malaria when administered therapeutically in the feed of
      chickens for 5-day periods, beginning on the day before infection, or on the day
      of infection, or up to four days after infection. Chickens were protected against
      mortality and reduction of weight gain. Three other criteria of efficacy, which
      showed good correlation with each other and also with the two commercial
      performance criteria, were the production of green diarrhoea (due to biliverdin),
      parasitaemia and reduced haematocrit values. When TMP/SQX treatments were
      initiated sooner than five days after infection, parasites were almost entirely
      eliminated from the blood, whereas treatments initiated later than four days
      after infection failed to protect birds against clinical disease. Birds protected
      by TMP/SQX against primary infection with P. gallinaceum were immune to clinical
      malaria when exposed to a severe blood-induced challenge of P. gallinaceum 28
      days later.

PMID- 15845275
TI  - Partial protection against tissue cysts formation in pigs vaccinated with crude
      rhoptry proteins of Toxoplasma gondii.
AB  - A vaccine containing crude Toxoplasma gondii rhoptry proteins incorporated in the
      immunostimulating complexes (ISCOM) adjuvant was tested in pigs for protecting
      against tissue cyst formation. For this, 38 mixed breed pigs were divided into
      four groups, G1 (vaccinated challenged, n=10) received two doses (100
      microg/dose) of the rhoptry vaccine at days 0 and 21, G2 (vaccinated challenged,
      n=10) received viable tachyzoites (7 x 10(7)) of the RH strain at day 0, G3
      (unvaccinated challenged, n=10) and G4 (unvaccinated unchallenged, n=8). Pigs
      were challenged with 4 x 10(4) VEG strain oocysts 57 days later. The G1 pigs
      produced high IgG antibody levels in the indirect enzyme-linked immunosorbent
      assay (ELISA) after the second dose of rhoptry vaccine, but were not clinically
      protected against a high dose oocyst challenge. Partial protection was observed
      in G1 at the chronic phase of infection, when compared with G3. Pigs in group 2
      developed high antibody levels and were protected against clinic signs. T. gondii
      was not detected in two (G1) and three (G2) pigs by mouse bioassay. The results
      indicate partial protection in pigs vaccinated with a rhoptry vaccine.

PMID- 15845276
TI  - PCR-based diagnosis for detection of Leishmania in skin and blood of rodents from
      an endemic area of cutaneous and visceral leishmaniasis in Brazil.
AB  - The technique of polymerase chain reaction (PCR) associated to hybridization was
      used to screen 123 samples collected from wild and synanthropic rodents captured
      in a cutaneous and visceral leishmaniasis endemic area in the State of Minas
      Gerais, Brazil. The detection of Leishmania spp in naturally infected rodents is
      of fundamental importance for incriminating them as possible reservoir hosts of
      the diseases in Minas Gerais. A total of 62 specimens belonging to wild
      (Thrichomys apereoides, Oryzomys subflavus, Galea spixii, Bolomys lasiurus and
      Wiedomys pyrrhorhinos) and synanthropic (R. rattus) rodent species were captured
      in different ecotopes. Blood and skin samples were submitted for PCR analyses
      followed by molecular hybridization with specific probes for the three Leishmania
      species complexes. Fifteen samples were found positive after PCR-hybridization
      and identified as follows: nine belonging to the L. mexicana complex, three to
      the L. braziliensis complex and three to the L. donovani complex. Positive PCR
      results were found in 11 out of the 61 (18%) blood samples and in four out of the
      62 (6.4%) skin fragments screened. R. rattus and T. apereoides were the most
      abundant species in the area also presenting high prevalence of natural
      infection. The presence of parasite DNA belonging to L. braziliensis, L. mexicana
      and L. donovani complexes was confirmed in several individuals of a rodent
      species, R. rattus. This work is the first report of the detection of L. (L.)
      chagasi in a naturally infected T. apereoides. The utility of filter paper as a
      substrate for PCR analyses and the efficacy of the procedure associated to the
      hybridization is emphasized.

PMID- 15845277
TI  - Anti-Hepatozoon canis serum antibodies and gamonts in naturally-occurring canine
      monocytic ehrlichiosis.
AB  - The prevalence of IgG antibodies to Hepatozoon canis and the presence of gamonts
      in the blood and hemolymphatic tissues were studied in dogs with canine monocytic
      ehrlichiosis (CME) caused by Ehrlichia canis. Both pathogens are transmitted by
      the tick Rhipicephalus sanguineus. Forty-five out of 69 (65.2%) dogs with CME
      were seropositive to H. canis by an enzyme-linked immunosorbent assay (ELISA).
      Intra-neutrophilic gamonts of H. canis were found in 2 out of 69 dogs (2.9%)
      comprising 4.5% of the seropositive dogs. The present study indicated that the
      prevalence of antibodies to H. canis was high among dogs with CME in an area
      where both infections are endemic. However, previous exposure to H. canis was not
      found as an important contributor to clinical or clinicopathologic abnormalities
      found in dogs with CME.

PMID- 15845278
TI  - Vaccination of older Bos taurus bulls against bovine babesiosis.
AB  - Two separate groups of Bos taurus bulls, one of 106 and the second of 27 animals,
      imported to Israel from areas free of Babesia bovis and Babesia bigemina, were
      vaccinated against babesiosis with a bivalent live attenuated vaccine. In light
      of the fact that routine vaccination is recommended at the weaning age, these
      bulls--of highly susceptible breeds--were kept under close surveillance to
      prevent losses that might be caused by severe clinical reactions to their
      vaccination at the age of 16-18 months. Seven days after vaccination, about one
      third of the 106 bulls in the first group developed clinical signs of B. bigemina
      infection, which peaked at day 9, and then diminished from day 11, when the
      patent period known for B. bovis infection was observed. Because of the severe
      clinical responses a total of 36% of the bulls required babesicidal treatment.
      Despite the treatment Babesia were not sterilized: 33 and 68% of the animals
      remained PCR positive for B. bigemina and B. bovis, respectively. To mitigate the
      severe responses to vaccination, the 27 bulls of the second group were vaccinated
      in two-steps: they were inoculated initially with avirulent culture-derived
      parasites and then vaccinated with the conventional donor-derived vaccine a month
      later. None of the bulls in the latter group developed clinical babesiosis, all
      were serologically positive to B. bigemina, and 67% showed seroconversion to B.
      bovis. In light of the experience described here, it is suggested that sensitive
      older cattle be vaccinated against babesiosis by priming them with avirulent in
      vitro-cultured parasites and then inoculating them with the conventional donor
      derived vaccines.

PMID- 15845279
TI  - Epidemiological aspects of canine visceral leishmaniosis in the Islamic Republic
      of Iran.
AB  - An epidemiological study to examine the sero-prevalence of zoonotic visceral
      leishmaniosis (ZVL) among domestic and wild canines in endemic foci of Iran was
      carried out during 1999-2003 to assess the distribution of the disease and the
      possible association between infection in dogs, wild canines and people. Anti
      leishmanial antibodies were detected by the direct agglutination test (DAT).
      Parasitological study was performed for all captured wild canines and were
      detected in some of the seropositive dogs with specific clinical signs (n=107).
      Serum samples (n=1568) were collected from domestic dogs in villages that are
      known endemic foci of human visceral leishmaniosis (HVL). Wild canine sera were
      collected from jackals (Canis aureus, n=10), foxes (Vulpes vulpes, n=10) and
      wolves (Canis lupus, n=10). Of the 1568 serum sampled collected from domestic
      dogs, 222 (14.2%) were positive by DAT (1:320 and above). No statistically
      significant difference was found between male (15.2%) and female (11.8%) sero
      prevalence (P=0.083). Dogs of 8 years and above showed the highest sero
      prevalence (40.6%). Only 23.9% of the seropositive domestic dogs had clinical
      signs. Parasitology and serology tests that were performed in 30 wild canines
      showed 10% these animals were infected by Leishmania infantum. Ten out of 11
      Leishmania spp. isolated from the dogs and wild canines were identified as L.
      infantum and one other as L. tropica by molecular and biochemical techniques. For
      the first time in Iran, L. infantum and L. tropica were isolated from viscera of
      both a wolf and a domestic dog.

PMID- 15845280
TI  - Isolation of Neospora caninum from naturally infected white-tailed deer
      (Odocoileus virginianus).
AB  - Attempts were made to isolate Neospora caninum from naturally infected white
      tailed deer (Odocoileus virginianus). A total of 110 deer killed during the 2003
      hunting season in Virginia region were used for the isolation of N. caninum. Of
      these, brains from 28 deer that had NAT titer of 1:200 were inoculated into
      interferon-gamma gene knock out (KO) mice. N. caninum was isolated from the
      tissues of three deer and all three isolates were mildly virulent to KO mice.
      Only one of the isolates could be adapted to in vitro growth. Protozoa in the
      tissues of KO mice reacted with N. caninum-specific polyclonal antibodies and N.
      caninum DNA was demonstrated in infected tissues by PCR assays; sequences of
      portions of the ITS-1 and gene 5 loci were identical to those in the public
      database. This is the first record of in vitro isolation of N. caninum from white
      tailed deer and lends credence to the white-tailed deer as an intermediate host
      for this parasite.

PMID- 15845281
TI  - Detection of Echinococcus multilocularis in wild boars in France using PCR
      techniques against larval form.
AB  - Recently, new data have been collected on the distribution and ecology of
      Echinococcus multilocularis in European countries. Different ungulates species
      such as pig, goat, sheep, cattle and horse are known to host incomplete
      development of larval E. multilocularis. We report a case of E. multilocularis
      portage in two wild boars from a high endemic area in France (Department of
      Jura). Histological examination was performed and the DNA was isolated from
      hepatic lesions then amplified by using three PCR methods in two distinct
      institutes. Molecular characterisation of PCR products revealed 99% nucleotide
      sequence homology with the specific sequence of the U1 sn RNA gene of E.
      multilocularis, 99 and 99.9% nucleotide sequence homology with the specific
      sequence of the cytochrome oxydase gene of Echinococcus genus and 99.9%
      nucleotide sequence homology with a genomic DNA sequence of Echinococcus genus
      for the first and the second wild boar, respectively.

PMID- 15845282
TI  - Molecular evidence of ovine (G1) and camel (G6) strains of Echinococcus
      granulosus in Tunisia and putative role of cattle in human contamination.
AB  - Three hundred and seventy-two cysts coming from 50 humans, 166 cattle, 153 sheep
      and 3 camels were collected in order to establish some epidemiological molecular
      information in Tunisia for the first time. The analysis by PCR-RFLP of ITS1
      sequence showed that all the human, ovine and bovine cysts were due to the common
      sheep strain of Echinococcus granulosus. The sequencing of the CO1 gene of 37
      isolates confirm the G1 genotype of this strain. For seven of these isolates, we
      found the mutation C56T which is present in the three principal intermediate
      hosts: human (three cysts), cattle (three cysts) and sheep (one cyst). With
      regard to the G1 genotype, we identified three other point mutations. The camel
      strain G6 is uniquely found in the three camels isolates and not in the other
      intermediate hosts analysed. The fertility of the bovine cyst represents 48% that
      means that this host is involved in a bovine-dog cycle and consequently
      represents a reservoir of sheep strain in Tunisia. Our results confirm the
      importance of the prophylaxis measures in order to disrupt the cycle of
      transmission sheep-dog in Tunisia. Nevertheless, the supervision of bovine
      infection should be reinforced because this intermediate host may constitute an
      important link with the human contamination.

PMID- 15845283
TI  - The effect of dietary polyunsaturated fatty acids (PUFA) on infection with the
      nematodes Ostertagia ostertagi and Cooperia oncophora in calves.
AB  - Diet-induced changes in the polyunsaturated fatty acid (PUFA) content of immune
      cells influences the immune phenotype that develops following infection. The aim
      of this study was to examine the effect of manipulating dietary PUFA supply on
      tissue fatty acids composition and immunity to a mixed infection with an abomasal
      and an intestinal nematode parasite in calves. Calves (n=24) were allocated into
      two treatment groups and fed 25 g/day of either fish oil (n-3 group) or a binary
      mixture of palm/rapeseed oil (normal group) as a supplement in milk replacer.
      Within each treatment group eight calves were infected with 2000 L3 Ostertagia
      ostertagi and Cooperia oncophora, three times per week for 8 weeks, the remaining
      calves were pair-fed uninfected controls. Faecal egg counts (FEC) were carried
      out twice weekly. At slaughter, the whole gut was removed intact for worm counts
      and tissue samples were taken for fatty acid analysis. Samples of abomasum,
      duodenum and mid-gut were also collected for immunohistological analysis. FEC
      were not significantly influenced by oil supplement but tended to remain higher
      in the palm/rapeseed oil-fed group (normal infected). The number of intestinal
      immature worms was significantly (p<0.05) higher in the n-3 group. Mucosal mast
      cell (MMC) and eosinophil numbers were significantly increased (p<0.05) by
      infection and were significantly lower (p<0.05) in the intestinal tissue of the
      fish oil supplemented and infected group (n-3 infected group). These results
      suggest that feeding an n-3 PUFA-rich supplement (fish oil) can influence
      cellular mediators of immunity to nematode infection. This is the first report of
      the establishment of patency and the subsequent development of immunity to a
      mixed infection with O. ostertagi and C. oncophora in calves undergoing early
      rumen development. The trend in the FEC, MMC and eosinophil numbers in the n-3
      group suggests that decreasing the dietary n-6/n-3 PUFA ratio may be a worthwhile
      immunonutritional strategy for potentiating the immune response to nematode
      parasite infection in the calf.

PMID- 15845284
TI  - Treatment of Baylisascaris procyonis infections in dogs with milbemycin oxime.
AB  - An examination was made as to the ability of Sentinel Flavor Tabs (milbemycin
      oxime/lufenuron) to treat Baylisascaris procyonis infections in dogs. The study
      was designed as a critical trial and included five naturally infected dogs and
      two dogs that were experimentally infected. Another dog from a prior clinical
      trial that was treated with Sentinel Flavor Tabs as part of the original FDA
      submission package for intestinal nematode infections was also included with the
      treated dogs. Of the five naturally infected dogs treated as part of the critical
      trial, three were cleared of their infections. These five dogs passed a total of
      52 worms after treatment; one dog retained 23 worms and the other retained 1 worm
      at necropsy 7 days after treatment. Two of five experimentally infected Beagle
      dogs that had been given mice that had been fed 200 infectious eggs, developed
      patent infections with the parasite. These dogs were treated, and one of the dogs
      passed one worm and the other passed two worms after treatment with no worms
      being detected at necropsy 7 days after treatment. The one dog that was treated
      with milbemycin oxime as part of the FDA submission was clear of worms at
      necropsy. Overall, the mean efficacy of Sentinel Flavor Tabs was found to be
      91.0%. Of the eight dogs that were treated, six were totally cleared of their
      infections, a cure rate of 75%. The two dogs that did not clear their infections
      had very large numbers of adult B. procyonis within their intestinal tracts at
      the time of treatment, one dog had 40 worms (23 remaining) and the other had 26
      worms (1 remaining). It is suggested that the treatment of dogs with monthly
      Sentinel Flavor Tabs could markedly reduce the chance of infected dogs
      contaminating the environment. Also, additional monthly treatments are highly
      likely to clear dogs of any worms not killed with the initial treatment.

PMID- 15845285
TI  - Real time PCR for the diagnosis of benzimidazole resistance in trichostrongylids
      of sheep.
AB  - This report describes a new molecular method for the diagnosis of benzimidazole
      susceptibility or resistance in three main species of trichostrongylids of sheep
      (Haemonchus contortus, Teladorsagia circumcincta and Trichostrongylus vitrinus).
      This assay is based on the use of real time polymerase chain reaction (PCR) to
      detect mutations of residue 200 on isotype 1 of beta-tubulin. The technique
      allows calculation of the proportion of each allelic variant as it combines
      kinetic (real time quantitative) PCR with allele-specific amplification and
      requires no post-PCR processing. The level of resistance in the population is
      determined by the proportion of the beta-tubulin codon 200 TAC allele. Hence, it
      was observed that the proportion of the resistant allele in susceptible strains
      ranged between 24% and 32.3%; in resistant strains this value increased to
      between 71.3% and 86.3%. Furthermore, there was a good correlation between real
      time PCR, faecal egg count reduction test, egg hatch assay and conventional
      allele-specific PCR, in both resistant and susceptible strains. A sensitive,
      rapid, highly reproducible and inexpensive technique for detecting resistance to
      benzimidazoles in a worm population has been developed.

PMID- 15845286
TI  - Morphological, histological, and ultrastructural studies of the ovary of the
      cattle-tick Boophilus microplus (Canestrini, 1887) (Acari: Ixodidae).
AB  - This study presents the morphology of the ovary, as well as the dynamics of the
      vitellogenesis process in oocytes of the cattle-tick Boophilus microplus. The
      ovary of these individuals is of the panoistic type; therefore, it lacks nurse
      cells. This organ consists of a single tubular structure, continuous, and
      composed of a lumen delimitated by a wall of small epithelial cells with rounded
      nuclei. In this tick species, the oocytes were classified into six stages varying
      from I to VI and according to: cytoplasm appearance and presence of the germ
      vesicle, yolk granules, and chorion. Oocytes of various sizes and at different
      developmental stages remain attached to the ovary through a cellular pedicel
      until completing stage V. Afterwards, they are liberated into the lumen and from
      there to the exterior. Some oocytes (classified as type VI) showed an atypical
      appearance indicating that some of the cellular components would be undergoing a
      degenerative process and/or reabsorption.

PMID- 15845287
TI  - Ectoparasites of road-killed vertebrates in northwestern South Carolina, USA.
AB  - Road-killed animals are overlooked as the source of ectoparasites for monitoring
      vectors of zoonotic pathogens. We demonstrate that by exclusively sampling road
      killed animals, a wide spectrum of vertebrate hosts and ectoparasites can be
      collected. Fifty-one species of ectoparasites were recovered from 35 species of
      road-killed vertebrates in northwestern South Carolina. Approximately, 11% of the
      total known terrestrial vertebrate species in the region were examined, which
      included more than 25% of the known mammal species. Our sampling techniques
      produced new state and regional records for chewing lice, ticks, and parasitic
      mites. Most ectoparasites were alive when they were collected, which would allow
      them to be screened for zoonotic pathogens.

PMID- 15845288
TI  - Dynamics of antibodies against hypodermin C in reindeer infested with the
      reindeer warble fly, Hypoderma tarandi.
AB  - Serum samples from 25 reindeer (Rangifer tarandus tarandus) were assayed for
      antibody against hypodermin C (HyC) using an ELISA. Nineteen animals were calves
      (born in 1998, 1999 or 2001) and six were adults (3-10 years old at first blood
      collection). The samples were collected over periods of 4 months (calves born in
      2001) or 27 months (adults and calves born in 1998 and 1999), the latter
      encompassing three Hypoderma tarandi infestation seasons. The calves received
      antibodies against HyC from their mothers, either by placental transfer or
      through the ingestion of colostrum. The low level at 3 h postpartum compared to
      the high level 3 days after birth in one calf suggests that the antibodies are
      transferred through colostrum. The levels of antibody of maternal origin
      decreased rapidly and reached low levels by mid-July, which coincides with the
      onset of the major Hypoderma ovipositioning season in this region. The calves
      thus did not appear to be protected by antibody against HyC when they were
      exposed to H. tarandi infestation for the first time. Antibody levels increased
      following infestation and reached a maximum during November or December, which
      coincides with when the H. tarandi larva stops migrating after it has reached the
      site under the skin of the back of the host and develops further. Levels declined
      thereafter and reached a nadir during the following summer. After the subsequent
      re-infestation, the increase in levels occurred at least 1 month earlier than
      with the first infestation. Levels remained elevated throughout the year after
      repeated infestations. This implies that the antibodies persist after the annual
      exit of mature larvae from the animal, and after larvae have been killed by
      application of ivermectin. Levels in adults, however, declined significantly with
      age, and levels were significantly lower in animals that were 4-11 years old than
      in 1-year-old animals during the same 1-year period. This supports the contention
      that the functional capacity of the immune system declines gradually with age.
      The study demonstrated that HyC is potentially useful for serological diagnosis
      of hypodermosis in reindeer, but the persistence of antibodies complicates
      interpretation of antibody-based surveillance programme data in all cases other
      than first-time exposure.

PMID- 15845289
TI  - Efficacy of fipronil in the treatment of feline cheyletiellosis.
AB  - The purpose of the present study was to confirm the efficacy of 10% (w/v)
      fipronil spot-on (Frontline spot-on for cats) in the treatment of feline
      cheyletiellosis under field conditions. A total of 16 cats of different breeds,
      sexes, 4 months to 14 years of age and weighing 0.5-6 kg were treated with a
      single topical application of 10% (w/v) fipronil spot-on according to label
      directions. The animals were naturally infested with Cheyletiella mites and
      housed in their normal environment throughout the study. Animals were selected
      based on clinical signs and infestation was confirmed by demonstration of mites.
      Mite counts and a clinical assessment of mite infestations (i.e. skin lesions
      and/or scales) were performed on days 0 and approximately days 14 and 28.
      Individual counts on day 0 ranged from 1 to 40 mites on individual animals. No
      mites were detected on cats treated with 10% (w/v) fipronil spot-on (Frontline
      spot-on for cats) at both post-treatment evaluations. Typical skin lesions and/or
      scales were present in all animals pre-treatment. In 56% of the cats, the lesions
      resolved within 14 days after treatment. At the final assessment, 75% cats were
      free of lesions. Two cats that still had clinical signs on day 28 were suspected
      of having allergic reactions to food or environmental allergens. The lesions on
      the remaining two cats could not be related to a specific cause. The efficacy of
      fipronil in elimination of mites was 100% on each occasion when compared to the
      pre-treatment count. The results of this study demonstrated that fipronil in a
      topical formulation is highly effective (100%) for the elimination of an existing
      Cheyletiella mite infestation under field conditions following a single topical
      application in cats.

PMID- 15845290
TI  - Occurrence of anti-Neospora caninum antibodies in Brazilian cervids kept in
      captivity.
AB  - Neospora caninum is a coccidian parasite that causes disease in captive and
      domesticated animals and has been found in wild animals such as cervids. Sera
      from 150 cervids of the genus Mazama, were collected from 31 captive herds and 16
      zoos from different Brazilian regions and analyzed by indirect fluorescent
      antibody test for anti-N. caninum antibodies. Positive reactions were found in
      42% (63) of the samples and the titers varied from 50 to 51,200. Of the 86
      cervids from the captive herds, 38 (44.2%) had anti N. caninum antibodies and of
      the 64 samples from the zoo, 25 (39.1%) were positive. No significant difference
      (p>0.05) was found for the occurrence values observed between the animals from
      captive herds and zoos as well as within the values documented for each one of
      the species analyzed. Therefore, the results indicate that the agent is prevalent
      from cervids in captivity in Brazil.

PMID- 15845291
TI  - Rapid selection for ivermectin resistance in Haemonchus contortus.
AB  - Lambs infected with two isolates, one British and one American, of Haemonchus
      contortus were treated with increasing doses of ivermectin. Eggs from the highest
      dose that had not eliminated the infection were cultured and larvae used to
      infect another lamb. After three generations the H. contortus was resistant to
      0.2 mg/kg ivermectin. The results stress the ease with which ivermectin
      resistance can be selected if high selection pressure is applied.

PMID- 15845292
TI  - SQAB 2004: finding the center.

PMID- 15845293
TI  - Simple heuristics and rules of thumb: where psychologists and behavioural
      biologists might meet.
AB  - The Centre for Adaptive Behaviour and Cognition (ABC) has hypothesised that much
      human decision-making can be described by simple algorithmic process models
      (heuristics). This paper explains this approach and relates it to research in
      biology on rules of thumb, which we also review. As an example of a simple
      heuristic, consider the lexicographic strategy of Take The Best for choosing
      between two alternatives: cues are searched in turn until one discriminates, then
      search stops and all other cues are ignored. Heuristics consist of building
      blocks, and building blocks exploit evolved or learned abilities such as
      recognition memory; it is the complexity of these abilities that allows the
      heuristics to be simple. Simple heuristics have an advantage in making decisions
      fast and with little information, and in avoiding overfitting. Furthermore,
      humans are observed to use simple heuristics. Simulations show that the
      statistical structures of different environments affect which heuristics perform
      better, a relationship referred to as ecological rationality. We contrast
      ecological rationality with the stronger claim of adaptation. Rules of thumb from
      biology provide clearer examples of adaptation because animals can be studied in
      the environments in which they evolved. The range of examples is also much more
      diverse. To investigate them, biologists have sometimes used similar simulation
      techniques to ABC, but many examples depend on empirically driven approaches.
      ABC's theoretical framework can be useful in connecting some of these examples,
      particularly the scattered literature on how information from different cues is
      integrated. Optimality modelling is usually used to explain less detailed aspects
      of behaviour but might more often be redirected to investigate rules of thumb.

PMID- 15845294
TI  - Spider heuristics.
AB  - Simple heuristics may help explain how even a spider, despite its minute brain,
      can be disturbingly intelligent. Hutchinson and Gigerenzer suggest that the
      generalist-specialist distinction (or more accurately the predictability
      unpredictability distinction) may be related to a species' level of reliance on
      simple heuristics, and spider behaviour may present some especially instructive
      opportunities for investigating these ideas. Daniel Dennett's distinction between
      Darwinian, Skinnerian and Popperian animals might be useful for discerning the
      different contexts in which optimality considerations and individual decision
      making are relevant.

PMID- 15845295
TI  - What are simple heuristics for studying simple heuristics?

PMID- 15845296
TI  - Simple optimisation.
AB  - Sometimes, an organism can use a simple optimisation heuristic. It does not need
      to calculate optimality functions, but can instead proceed by evaluating
      gradients in its environment and following a path that leads towards a local
      maximum or minimum.

PMID- 15845297
TI  - Empirical tests of "Take-the-Best" with non-human subjects.
AB  - The fast and frugal heuristics of ABC and rules of thumb of behavioural
      biologists represent strategies that humans and other animals might use to make
      decisions under time constraints and with a minimum of information. If
      experimental psychologists could demonstrate use of simple heuristics by non
      humans in experimental settings, quantitative and empirical evaluation of those
      heuristics would benefit from additional formal, controlled avenues of study.

PMID- 15845298
TI  - Heuristics and general principles of learning.
AB  - This research on decision-making heuristics is similar to research on animal
      learning in at least two ways. First, optimality modeling has not proven to be
      very useful for either research area. Second, both of these research areas seek
      to find general principles (or heuristics) that are applicable to different
      species in different settings. However, the basic principles of classical and
      operant conditioning seem to be more uniform across species and situations,
      whereas decision-making heuristics can vary for different species and different
      situations, even for tasks with very similar characteristics.

PMID- 15845299
TI  - Exorcising demons.
AB  - ABC claims to have exorcised the demons associated with optimality-based models
      of decision making. Fast and frugal heuristics appear to provide elegant, yet
      relatively simple, descriptions of a variety of behavior patterns, including
      those that some behavioral ecologists attribute to "rules of thumb." I worry,
      however, that the notion of ecological rationality fails to provide an adequate
      framework for characterizing the etiologies of behavior patterns described by
      ABC's heuristics. Thus, demons may still lurk. These demons could be exorcised, I
      believe, by incorporating the functional analyses characteristic of the
      experimental analysis of behavior.

PMID- 15845300
TI  - All thumbs?
AB  - In this otherwise insightful line of investigation, some aspects of rules of
      thumb (RoT) remain underspecified: their evolution and function, how they are
      selected for a task, how they are learned, and the dependence of their apparent
      simplicity on their embodiment and context. Theories of operant and respondent
      conditioning may serve as the theoretical framework required to flesh out those
      details.

PMID- 15845301
TI  - Taking the best for learning.
AB  - Examples of how animals learn when multiple, sometimes redundant, cues are
      present provide further examples not considered by Hutchinson and Gigerenzer that
      seem to fit the principle of taking the best. "The best" may the most valid cue
      in the present circumstances; evolution may also produce species-specific biases
      to use the most functionally relevant cues.

PMID- 15845302
TI  - The rules we choose by.
AB  - Hutchinson & Gigerenzer's functional approach to decision making has much in
      common with behavioral approaches. One of their central points is that "rules-of
      thumb" often provide efficient decision strategies, use of which is both rational
      and generally optimal. We agree, but also caution that the misapplication of
      rules sometimes leads to non-optimal decisions.

PMID- 15845303
TI  - Heuristics or general learning processes?
AB  - The concept of heuristics implies that the rules governing choice behavior may
      vary with ecological constraints. Behavior analysis, in contrast, seeks general
      principles that transcend specific situations. To the extent that search is
      successful, the concept of heuristics is unlikely to play a significant role in
      the analysis of animal behavior.

PMID- 15845305
TI  - Decision-making: Context matters.
AB  - Research and theory in human decision-making has increasingly stressed the
      importance of the context in which the problem is embedded. This emphasis is
      consistent with that supported by research of behavior analysts on natural
      concept formation and in problem solving, as well as in the study of choice. We
      present data on reasoning problems that further support the role of context in
      decision-making.

PMID- 15845306
TI  - Delay discounting of real and hypothetical rewards III: steady-state assessments,
      forced-choice trials, and all real rewards.
AB  - Human research in delay discounting has omitted several procedures typical of
      animal studies: forced-choice trials, consequences following each response, and
      assessment of stable response patterns. The present study manipulated these
      procedures across two conditions in which real or hypothetical rewards were
      arranged. Six college students participated in daily sessions, in which steady
      state discounting of hypothetical and real rewards was assessed. No systematic
      effects of repeated exposure to hypothetical rewards was detected when compared
      with first day assessments of discounting. Likewise, no systematic effect of
      reward type (real versus hypothetical) was detected. When combined with previous
      research failing to detect a difference between hypothetical and potentially real
      rewards, these findings suggest that assessing discounting of hypothetical
      rewards in single sessions is a practical and valid procedure in the study of
      delay discounting.

PMID- 15845307
TI  - How rats combine temporal cues.
AB  - The procedures for classical and operant conditioning, and for many timing
      procedures, involve the delivery of reinforcers that may be related to the time
      of previous reinforcers and responses, and to the time of onsets and terminations
      of stimuli. The behavior resulting from such procedures can be described as bouts
      of responding that occur in some pattern at some rate. A packet theory of timing
      and conditioning is described that accounts for such behavior under a wide range
      of procedures. Applications include the food searching by rats in Skinner boxes
      under conditions of fixed and random reinforcement, brief and sustained stimuli,
      and several response-food contingencies. The approach is used to describe how
      multiple cues from reinforcers and stimuli combine to determine the rate and
      pattern of response bouts.

PMID- 15845308
TI  - The role of common reinforced comparison responses in acquired sample
      equivalence.
AB  - Different samples occasioning the same reinforced comparison response in matching
      to-sample are interchangeable for one another outside of original training. The
      present studies were designed to verify the role of these common responses in
      producing acquired sample equivalence by explicitly varying the presence or
      absence of this commonality during training. In each of the two experiments, one
      group of pigeons made the same reinforced choice response following multiple
      sample stimuli, whereas controls either made different reinforced choices
      following each sample (Experiment 1) or reinforced choices after only two of four
      center-key stimuli (Experiment 2). Later, two of the original samples/center-key
      stimuli were established as conditional cues for new comparison responses, after
      which the ability of the remaining samples/center-key stimuli to occasion those
      new responses was assessed. Following common-response training, matching accuracy
      was higher on class-consistent than on class-inconsistent transfer tests, whereas
      accuracy in the controls was generally intermediate between these two extremes, a
      pattern similar to that reported in the human paired-associate literature. These
      findings confirm that occasioning the same reinforced choice response is one
      means by which disparate samples become functionally equivalent.

PMID- 15845309
TI  - Primacy and recency effects in extinction and latent inhibition: a selective
      review with implications for models of learning.
AB  - In the framework of animal conditioning and human associative learning, primacy
      and recency effects on acquired stimulus control of behavior refer to the
      superior influence of first-learned and last-learned associations, respectively.
      Most contemporary associative models of learning anticipate unwavering recency
      effects and claim support from numerous published studies. But, for pragmatic
      reasons, almost all of these studies were conducted under select conditions that
      favored recency effects. When these conditions are not met, recency effects are
      far from ubiquitous. We review the literature on primacy and recency effects
      regarding extinction and latent inhibition (i.e., interference between outcomes),
      with special emphasis on the impact of certain post-training manipulations and
      test conditions on conditioned responding. Evidence for recency-to-primacy shifts
      and for memory integration is examined in light of contemporary models of
      learning.

PMID- 15845310
TI  - Windows.
AB  - Some models of performance assume that behavior depends on environmental
      quantities (for example, rates of reinforcement) that are defined over intervals
      of fixed duration. Although such window models may serve as useful
      approximations, they are incompatible with well-known properties of behavior (for
      instance, sensitivity to delay). Window models with variable window length,
      however, are more difficult to refute. This article examines some implications of
      the assumption of random window length. Variable windows are shown to produce
      continuous forgetting and temporal discounting functions, to display properties
      analogous to parallel aggregation, and to make reasonable predictions about
      steady-state relations between reinforcement and responding. Issues of
      interpretation nonetheless suggest that alternatives to window models should be
      developed.

PMID- 15845311
TI  - Theoretical note: the C/T ratio in artificial neural networks.
AB  - This paper describes computer simulations of the effect of the C/T ratio on
      acquisition rate in artificial neural networks. The networks consisted of neural
      processing elements that functioned according to a neurocomputational model whose
      learning rule is consistent with information on dopaminergic mechanisms of
      reinforcement. In Simulation 1, three comparisons were made: constant C and
      variable T, variable C and constant T, and a constant C/T with variable C and T.
      In the last two comparisons, C was manipulated by changing the probability of
      reinforcement within the intertrial interval (ITI), in the absence of the
      conditioned stimulus (CS). Acquisition rate tended to increase with C/T, and the
      invariant ratio had no effect. In Simulation 2, C was manipulated by changing the
      ITI, with continuous reinforcement in the presence of the CS and no
      reinforcements in its absence. Results were comparable to those obtained in
      Simulation 1. Simulation 3 further explored the effect of the invariant ratio,
      but with larger absolute values of C and T, which slowed acquisition
      significantly. The results parallel some experimental findings and theoretical
      implications of the Gibbon-Balsam model, showing that they can emerge from the
      moment-to-moment dynamics of a neural-network model. In contrast to that model,
      however, Simulation 3 suggests that the effect of invariant C/T ratios may be
      bounded.

PMID- 15845312
TI  - The operant reserve: a computer simulation in (accelerated) real time.
AB  - In Skinner's Reflex Reserve theory, reinforced responses added to a reserve
      depleted by responding. It could not handle the finding that partial
      reinforcement generated more responding than continuous reinforcement, but it
      would have worked if its growth had depended not just on the last response but
      also on earlier responses preceding a reinforcer, each weighted by delay. In that
      case, partial reinforcement generates steady states in which reserve decrements
      produced by responding balance increments produced when reinforcers follow
      responding. A computer simulation arranged schedules for responses produced with
      probabilities proportional to reserve size. Each response subtracted a fixed
      amount from the reserve and added an amount weighted by the reciprocal of the
      time to the next reinforcer. Simulated cumulative records and quantitative data
      for extinction, random-ratio, random-interval, and other schedules were
      consistent with those of real performances, including some effects of history.
      The model also simulated rapid performance transitions with changed contingencies
      that did not depend on molar variables or on differential reinforcement of inter
      response times. The simulation can be extended to inhomogeneous contingencies by
      way of continua of reserves arrayed along response and time dimensions, and to
      concurrent performances and stimulus control by way of different reserves created
      for different response classes.

PMID- 15845313
TI  - Ian Stolerman service as editor for Drug and Alcohol Dependence.

PMID- 15845314
TI  - Self-injection of flunitrazepam alone and in the context of methadone maintenance
      in baboons.
AB  - Patients in methadone maintenance programs use benzodiazepines to "boost"
      methadone's subjective effects, and flunitrazepam has been prominent in this
      context. Self-administration of flunitrazepam (0.001-0.32 mg/kg i.v.) alone and
      during daily oral methadone administration was evaluated in three baboons.
      Flunitrazepam maintained self-injection as an inverted U-shaped function of dose
      at rates higher than those maintained by most other benzodiazepines under the
      same procedure. In the context of demonstrated physical dependence on 3.2
      mg/kg/day p.o. methadone, flunitrazepam doses on the ascending limb of the dose
      effect curve maintained greater rates of self-injection than before methadone in
      two baboons. When the methadone dose decreased to 1.8 mg/kg/day, self-injection
      remained higher for those baboons and became higher than before methadone for the
      third baboon. Self-injection remained higher when methadone decreased to 1.0
      mg/kg/day, except self-injection of the lowest flunitrazepam dose returned to or
      below the pre-methadone rate for two baboons. After methadone was discontinued,
      the dose-effect curve shifted to the right in one baboon but remained to the left
      in two. Flunitrazepam thus served as a reinforcer alone and in the context of
      methadone maintenance. Lower doses maintained higher self-injection during and
      shortly after methadone maintenance. Further research should explore the duration
      of higher self-injection rates following methadone maintenance.

PMID- 15845315
TI  - Behavioral treatment approaches for methamphetamine dependence and HIV-related
      sexual risk behaviors among urban gay and bisexual men.
AB  - BACKGROUND: Methamphetamine-dependent gay and bisexual men (GBM) are at high risk
      for HIV transmission, largely due to drug-associated sexual risk behaviors. This
      project evaluated the efficacy of four behavioral drug abuse treatments for
      reducing methamphetamine use and sexual risk behaviors among this population.
      METHODS: In this randomized controlled trial, 162 methamphetamine-dependent (SCID
      verified) GBM in Los Angeles County were randomly assigned to one of four
      treatment conditions for 16 weeks: standard cognitive behavioral therapy (CBT,
      n=40), contingency management (CM, n=42), combined cognitive behavioral therapy
      and contingency management (CBT+CM, n=40), and a culturally tailored cognitive
      behavioral therapy (GCBT, n=40). Stimulant use was assessed thrice-weekly during
      treatment using urine drug screens (48 measures). Sexual risk behaviors were
      monitored monthly (four measures). Follow-up assessments were conducted at 6
      (80.0%) and 12 months (79.9%). RESULTS: Statistically significant differences in
      retention (F(3,158)=3.78, p<.02), in longest period of consecutive urine samples
      negative for methamphetamine metabolites (F(3,158)=11.80, p<.001), and in the
      Treatment Effectiveness Score were observed by condition during treatment
      (F(3,158)=7.35, p<.001) with post hoc analyses showing the CM and CBT+CM
      conditions to perform better than standard CBT. GEE modeling results showed GCBT
      significantly reduced unprotected receptive anal intercourse (URAI) during the
      first 4 weeks of treatment (X2=6.75, p<.01). During treatment between-group
      differences disappeared at follow-up with overall reductions in outcomes
      sustained to 1-year. CONCLUSIONS: Among high-risk methamphetamine-dependent GBM,
      drug abuse treatments produced significant reductions in methamphetamine use and
      sexual risk behaviors. Drug abuse treatments merit consideration as a primary HIV
      prevention strategy for this population.

PMID- 15845316
TI  - A comparison of the reinforcing efficacy of 3,4-methylenedioxymethamphetamine
      (MDMA, "ecstasy") with cocaine in rhesus monkeys.
AB  - The purpose of the present study was to compare the reinforcing efficacy of 3,4
      methylenedioxymethamphetamine (MDMA, 'ecstasy') to cocaine. Rhesus monkeys (n=4)
      responded under a within-session, exponentially increasing, progressive-ratio
      (PR) schedule of cocaine reinforcement. Breaking point (BP) for the PR schedule
      was defined as the final response requirement completed before 2 h had elapsed
      without an injection delivered. Saline and doses of cocaine (0.003-0.3
      mg/kg/injection) and MDMA (0.01-0.56 mg/kg/injection) were substituted for the
      training dose of cocaine for at least five consecutive sessions. Both cocaine and
      MDMA functioned as reinforcers, but self-administration of MDMA occurred at fewer
      doses and a significantly lower peak BP was obtained for MDMA. These data
      demonstrate that MDMA functions as a reinforcer, although its reinforcing
      efficacy appears to be less than that of cocaine.

PMID- 15845317
TI  - HIV infection among female drug users in Northern Thailand.
AB  - Reports on HIV infection and risk behaviors among female drug users in developing
      countries, particularly in Asia, are limited. In this study, we investigated HIV
      prevalence and risk factors for HIV infection among 200 women admitted for 21-day
      inpatient drug detoxification in Chiang Mai, Thailand. Volunteers completed a
      face-to-face interview using a structured interview, HIV pre-test counseling,
      specimen collection for HIV and STD tests, and were provided test results and HIV
      post-test counseling 1 week later. Two-third of participants (68%) were ethnic
      minorities with no formal education. Overall, 14 (7%) were HIV positive: 25%
      among 28 heroin injectors and 4.1% among 172 opium or methamphetamine smokers
      (p<0.001). History of drug injection and sexual abuse were associated with HIV
      infection. HIV prevention strategies for drug-using women in Thailand should
      consider both harm reduction strategies for drug use and promoting safer sex
      measures in a culturally appropriate context.

PMID- 15845318
TI  - Respondent-driven sampling to recruit MDMA users: a methodological assessment.
AB  - Recruiting samples that are more representative of illicit drug users is an on
      going challenge in substance abuse research. Respondent-driven sampling (RDS), a
      new form of chain-referral sampling, is designed to eliminate the bias caused by
      the non-random selection of the initial recruits and reduce other sources of bias
      (e.g. bias due to volunteerism and masking) that are usually associated with
      regular chain-referral sampling. This study provides a methodological assessment
      of the application of RDS among young adult MDMA/ecstasy users in Ohio. The
      results show that the sample compositions converged to equilibrium within a
      limited number of recruitment waves, independent of the characteristics of the
      initial recruits (i.e. seeds). The sample compositions approximated the
      theoretical equilibrium compositions, and were not significantly different from
      the estimated population compositions-with the exception that White respondents
      were over-sampled and Black respondents were under-sampled. The effect of
      volunteerism and masking on the sampling process was found not to be significant.
      Though identifying productive seeds and improving the referral rate are
      significant challenges when implementing RDS, the findings demonstrate that RDS
      is a flexible and robust sampling method. RDS has the potential to be widely
      employed in studies of illicit drug-using populations.

PMID- 15845319
TI  - Experience of emotions in substance abusers exposed to images containing neutral,
      positive, and negative affective stimuli.
AB  - There is emerging evidence that suggests emotional processes may be involved in
      the development of addiction, and that emotional alterations may compromise the
      effectiveness of treatment approaches in substance abuse. Nonetheless, there is a
      dearth of studies that have examined the experience of emotions in substance
      abusers, especially with regard to natural affective stimuli that are
      motivationally relevant for the normal population. The main aims of this study
      are: (a) to examine possible differences in the experience of emotions of drug
      free substance abusers exposed to images containing motivationally relevant
      stimuli, with regard to a normal population and (b) to examine possible
      differences in the experience of emotions of substance abusers depending on their
      drug of choice. We used 25 images from the International Affective Picture System
      (IAPS) to elicit different emotional states, and the Self Assessment Manikin
      (SAM) to record participants' subjective experience on three emotional
      dimensions: valence, arousal, and dominance. We used bifactorial MANOVA to
      examine subjective emotional ratings as a function of group, and as a function of
      the kind of image shown. Results showed a differential emotional profile of
      substance abusers with regard to healthy controls; and different emotional
      profiles between abusers of a number of substances. These results suggest the
      experience of emotions may be significantly altered in substance abusers, and
      that these alterations may play an important role in drug abuse treatment course
      and results.

PMID- 15845320
TI  - Predictors of health functioning in two high-risk groups of smokers.
AB  - The relative and combined health effects of cigarette smoking, heroin use, and
      depression were examined in 322 clinically depressed smokers and 117 opioid
      dependent smokers participating in two studies of the San Francisco Treatment
      Research Center. Opioid-dependent smokers averaged 16 years (S.D.=9) of heroin
      use; 3% of depressed smokers used opiates in the past 6 months. Cigarettes per
      day (M=15, S.D.=10) and Beck Depression (BDI-II) scores (M=21, S.D.=11) were
      comparable between the two groups. Health functioning was assessed using the
      Medical Outcomes Study Short Form (SF-36). Adjusting for demographic differences,
      depressed smokers reported better physical but poorer emotional health relative
      to opioid-dependent smokers. Both groups scored significantly lower than
      published norms (p<.05). Within groups, severity of depressive symptoms, tobacco
      use, and opiate use were independent predictors of lower health functioning
      (p<.05). Examining risk-related subgroups based on depression scores (BDI-II> or
      =20), cigarettes per day (> or =1 pack), and opiate use, number of risk factors
      was monotonically related to health functioning in both samples. Individuals with
      two or more risk factors scored the lowest (p<.05). Severity of depressive
      symptoms, tobacco use, and opiate use contributed individually and collectively
      to lower health functioning. Blended treatments that target multiple risk factors
      are needed to improve health outcomes.

PMID- 15845321
TI  - Attempted suicide among heroin users: 12-month outcomes from the Australian
      Treatment Outcome Study (ATOS).
AB  - A cohort of 495 heroin users, recruited for the Australian Treatment Outcome
      Study (ATOS), were re-interviewed at 12 months regarding suicide attempts over
      the follow-up period. The proportion who had attempted suicide in the 12 months
      since baseline was not significantly different from that reported in the 12
      months preceding ATOS enrolment (12.2% versus 9.1%), and attempted suicide did
      not decline significantly in any of the index treatment groups. Among males,
      there was no significant reduction in attempted suicide (8.7% versus 8.1%). Among
      females, however, the proportion reporting an attempt declined significantly from
      19.7 to 9.8%. Of those who reported suicidal ideation at baseline, 22.8% made an
      attempt over the follow-up period, as did 19.0% of those who had major
      depression. Large, and significant, declines in suicidal ideation (23.1% versus
      6.9%) and major depression (25.5% versus 10.9%) occurred over the study period.
      Independent predictors of a suicide attempt over the follow-up period were:
      social isolation, having made an attempt in the preceding 12 months, suicidal
      ideation at baseline, a greater number of treatment episodes and higher levels of
      baseline polydrug use.

PMID- 15845322
TI  - Genetic influences on quantity of alcohol consumed by adolescents and young
      adults.
AB  - OBJECTIVE: To examine genetic and environmental influences on drinking in a
      nationally representative study of genetically informative adolescents followed
      into young adulthood. METHOD: The average quantity of alcohol used per drinking
      episode during the past year was analyzed in 4432 youth assessed during
      adolescence (mean age of 16) and then 1 and 6 years later. The variance of
      quantity of alcohol consumed was decomposed into three components: additive
      genetic (a2), shared environmental (c2), non-shared environmental (e2). Four
      candidate genes were tested for association. RESULTS: Wave 1 a2-0.52e2-0.48, Wave
      2 a2-0.28e2-0.72, Wave 3 a2-0.30e2-0.70. Genetic correlations between Waves 1 and
      2 were 0.85, Waves 1 and 3 were 0.34. The DAT1 440 allele was associated at Wave
      1 (p=0.007). DRD2 TaqI A1/A2 was associated at Wave 3 (p=0.007). DRD4 and 5HTT
      were not associated. The DAT1 and DRD2 polymorphisms accounted for 3.1% and 2.0%
      of the variation, respectively. CONCLUSION: Genetic influence on drinking
      behavior was common in adolescents longitudinally assessed 1 year apart, but was
      less correlated between these adolescents and their assessment as young adults at
      a subsequent time point. Polymorphisms in genes of the dopaminergic system appear
      to influence variation in drinking behavior.

PMID- 15845323
TI  - Decomposing the total variation in a nested random effects model of neighborhood,
      household, and individual components when the dependent variable is dichotomous:
      implications for adolescent marijuana use.
AB  - Multilevel modeling techniques have become a useful tool that enables substance
      abuse researchers to more accurately identify the contribution of multiple levels
      of influence on drug-related attitudes and behaviors. However, it is difficult to
      determine the relative importance of the different hierarchical levels because,
      in the case of dichotomous outcomes, the variance components estimation involves
      calculations using a log-odds metric at the lowest level of estimation. We
      present methods introduced by Goldstein and Rasbash [Goldstein, H., Rasbash, J.,
      1996. Improved approximations for multilevel models with binary responses. J.
      Roy. Stat. Soc. A 159, 505-513.] to convert the variance components from the log
      odds to the probability metric. This method provides a more logical and
      interpretable way to examine variation for nonlinear outcomes, which tend to be
      heavily utilized in substance use research. Using data from the National
      Household Survey on Drug Abuse [Substance Abuse and Mental Health Services
      Administration (SAMHSA), 2001. 1999 National Household Survey on Drug Abuse. Data
      Collection Final Report. Office of Applied Studies (OAS), Rockville, MD.
      Available at . Accessed on July 1, 2003.], we partition variation among
      individual, household, and neighborhood levels for the binary outcome of past
      year marijuana use to illustrate this approach. We also conduct a stability
      analysis to examine the robustness across different estimation procedures
      commonly available in commercial multilevel software packages. Finally, we
      partition the variance components using a conventional continuously distributed
      outcome and compare the relative magnitudes across binary and continuous
      outcomes.

PMID- 15845324
TI  - Cannabis withdrawal in adolescent treatment seekers.
AB  - A valid cannabis withdrawal syndrome has been demonstrated in controlled studies
      with adult marijuana abusers, yet few published reports have examined cannabis
      withdrawal among adolescents. Adolescents presenting for outpatient substance
      abuse treatment, whose primary substance of abuse was cannabis, completed a
      questionnaire reporting the presence and severity of withdrawal symptoms during
      past periods of cannabis abstinence. Nearly two-thirds of the sample indicated
      that they had experienced four or more symptoms, and over one-third reported four
      or more symptoms that occurred at a moderate or greater severity. The magnitude
      of withdrawal severity was positively correlated with current emotional and
      behavioral symptoms and self-reported problems with cannabis use. These findings
      are consistent with previous studies, though the prevalence and magnitude of
      withdrawal symptoms were lower than that observed in a similar study with adult
      treatment seekers [Budney, A.J., Novy, P., Hughes, J.R., 1999. Marijuana
      withdrawal among adults seeking treatment for marijuana dependence. Addiction 94,
      1311-1322]. Further research is needed to elucidate associations between cannabis
      withdrawal effects, the initiation of cessation attempts, and relapse.

PMID- 15845325
TI  - Urge-specific and lifestyle coping strategies of cocaine abusers: relationships
      to treatment outcomes.
AB  - This study investigated specific coping techniques for effectiveness in reducing
      cocaine use after treatment. The urge-specific strategies questionnaire-cocaine
      (USS-C) assessed frequency of use of 21 strategies for coping with urges. The
      general change strategies questionnaire-cocaine (GCS-C) assessed frequency of use
      of 21 lifestyle change strategies designed to maintain abstinence. Cocaine
      dependent patients were assessed at follow-up after residential treatment for USS
      C (n=59 at 3 months, 84 at 6 months), GCS-C (n=89 at 3 months, 120 at 6 months)
      and substance use. Less cocaine use was associated with urge coping by thinking
      about negative or positive consequences, alternative behaviors, distraction,
      relaxation/meditation, escape, offer refusal, spiritual methods, behavior chains,
      mastery messages, problem-solving, meeting or sponsor, or seeking social support.
      The lifestyle change strategies of thinking about consequences, working toward
      goals, thinking of oneself as sober, clean recreation, regular relaxation,
      avoiding temptations, not carrying much money, living with clean people, seeking
      social support, spiritual involvement, keeping busy, and health activities were
      also associated with less cocaine use. Results suggest focusing coping skills
      training on these potentially effective strategies.

PMID- 15845326
TI  - Inhibition of gap junction currents by the abused solvent toluene.
AB  - Abused inhalants are a large class of compounds that are inhaled for their
      intoxicating and mood altering effects. They include chemicals with known
      therapeutic uses such as anesthetic gases as well as volatile organic solvents
      like toluene that are found in paint thinners and adhesives. Because of their
      widespread commercial use and availability, inhalants are often among the first
      drugs that children encounter and use of these compounds is often associated with
      adverse acute and long-term consequences. The cellular and molecular sites of
      action for abused inhalants is not well known although recent studies report that
      toluene and other organic solvents alter the activity of specific ligand- and
      voltage-gated ion channels that regulate cellular excitability. As part of an
      ongoing effort to define molecular sites of action for abused inhalants, this
      study examined the effect of toluene on the function of gap junction proteins
      endogenously expressed in human embryonic kidney (HEK 293) cells. Gap junctions
      allow cell-to-cell electrical communication as well as passage of small molecular
      weight substances and are critical for synchronizing cellular activity in certain
      tissues. Gap junction currents in HEK 293 cells were measured during brief
      voltage steps using patch-clamp electrophysiology and were blocked by known gap
      junction blockers confirming expression of connexin proteins in these cells.
      Toluene dose-dependently inhibited these conductances with threshold effects
      appearing at approximately 0.4 mM and near complete inhibition occurring at
      concentrations of 1 mM and higher. The estimated EC50 value for toluene
      inhibition of gap junction currents in HEK 293 cells was 0.57 mM. The results of
      these studies suggest that volatile solvents including toluene may produce some
      of their effects by disrupting inter-cellular communication mediated by gap
      junction proteins.

PMID- 15845327
TI  - Opioid abuse and cognitive performance.
AB  - A few recent studies provide evidence for performance impairment in dependent
      opioid abusers enrolled in methadone maintenance programs. However, it is
      difficult to differentiate the effects of a history of long-term opioid (or
      polydrug) abuse from the effects of methadone maintenance itself. The purpose of
      the present study was to address this issue by comparing the performance of a
      newly recruited group of 20 currently abstinent former opioid abusers
      retrospectively to two groups (18 methadone maintenance patients (MMP); 21
      matched non-drug abusing controls) reported on previously in our laboratory
      [Mintzer, M.Z., Stitzer, M.L., 2002. Cognitive impairment in methadone
      maintenance patients. Drug Alcohol Depend. 67, 41-51], using the same performance
      testing battery. The abstinent abusers were demographically similar to the MMP
      and matched controls, and reported histories of drug use similar to those of the
      MMP. Although conclusions are somewhat limited by the small sample size,
      performance of the abstinent abusers fell between that of the MMP and controls on
      many measures, suggesting that methadone maintenance may be associated with
      additional impairment over and above that associated with long-term abuse, and
      that recovery of functioning may occur during abstinence. Further research is
      necessary to explore the factors underlying performance impairment in MMP and to
      determine the clinical significance of the observed impairments for daily
      performance in the natural environment.

PMID- 15845328
TI  - On the survival of the altruistic trait in medicine: is there a link with the
      placebo effect?

PMID- 15845329
TI  - Multivariate models of self-reported health often neglected essential candidate
      determinants and methodological issues.
AB  - BACKGROUND AND OBJECTIVE: Self-reported health is an important indicator of
      overall well-being that may be influenced by diverse parameters. We intended to
      evaluate the variety of candidate determinants used in models of self-reported
      health (SRH) and to examine the methodological problems encountered in
      multivariate models used in recent studies in this field. STUDY DESIGN AND
      SETTING: Medline searches identified articles published in 2002 in which SRH was
      included as an outcome, at least one other variable was used as a determinant of
      SRH, and the study population was not defined by the presence of specific
      diseases. RESULTS: Of 1,991 initially identified reports, 56 were eligible. In
      91% of the eligible articles, multivariate models were used. In total, 133
      different determinants of SRH were considered (median 7 determinants considered
      per study with multivariate models). The proportions of studies with problems in
      multivariate modeling were: overfitting, 10%; nonconformity to a linear gradient,
      29%; no report of tests for interactions, 63%; unspecified coding of variables,
      49%; and unspecified selection of variables, 29%. CONCLUSION: Models that try to
      identify what influences SRH should consider appropriate lists of candidate
      determinants, with proper attention to methodological aspects of multivariate
      modeling.

PMID- 15845330
TI  - Identifying studies for systematic reviews of diagnostic tests was difficult due
      to the poor sensitivity and precision of methodologic filters and the lack of
      information in the abstract.
AB  - BACKGROUND AND OBJECTIVES: Methods to identify studies for systematic reviews of
      diagnostic accuracy are less well developed than for reviews of intervention
      studies. This study assessed (1) the sensitivity and precision of five published
      search strategies and (2) the reliability and accuracy of reviewers screening the
      results of the search strategy. METHODS: We compared the results of the search
      filters with the studies included in two systematic reviews, and assessed the
      interobserver reliability of two reviewers screening the list of articles
      generated by a search strategy. RESULTS: In the first review, the search strategy
      published by van der Weijden had the greatest sensitivity, and in the second,
      four search strategies had 100% sensitivity. There was "substantial" agreement
      between two reviewers, but in the first review each reviewer working on their own
      would have missed one paper eligible for inclusion in the review. Ascertainment
      intersection techniques indicate that it is unlikely that further papers have
      been missed in the screening process. CONCLUSION: Published search strategies may
      miss papers for reviews of diagnostic test accuracy. Papers are not easily
      identified as studies of diagnostic test accuracy, and the lack of information in
      the abstract makes it difficult to assess the eligibility for inclusion in a
      systematic review.

PMID- 15845331
TI  - New patient-oriented diagnostic test characteristics analogous to the likelihood
      ratios conveyed information on trustworthiness.
AB  - OBJECTIVE: Suggesting patient-oriented ratio measures of diagnostic tests
      analogous to the likelihood ratios. STUDY DESIGN AND SETTING: Algebraic equation
      based on Bayes' theorem. RESULTS: Two new measures are suggested: the positive
      predictive ratio (PPR), relating the positive predictive value (PPV) to the false
      negative rate in the patient population, and the negative predictive ratio (NPR),
      relating the negative predictive value (NPV) to the false positive rate in the
      patient population. The new measures are analogous to likelihood ratios. These
      measures are calculable from the familiar 2x2 table in a selected study
      population or in a target (general) population. Examples are given, using
      published data. CONCLUSION: PPR adds to the information given by the PPV, and NPR
      adds to the information given by the NPV. PPR and NPR may be more appropriate in
      the clinical setting than likelihood ratios.

PMID- 15845332
TI  - The standard gamble demonstrated lower reliability than the feeling thermometer.
AB  - BACKGROUND AND OBJECTIVE: Participants rated clinical marker states (CMS) to make
      respondents familiar with the task of preference instruments, ground their
      ratings in relation to other health states, and help investigators interpret
      patient ratings. The objective was to assess the reliability of CMS using
      appropriate reliability statistics. STUDY DESIGN AND SETTING: Eighty-one patients
      rated CMSs for mild, moderate, and severe chronic respiratory disease using the
      feeling thermometer (FT) and the standard gamble (SG) before and after a 3-month
      respiratory rehabilitation program. To assess reliability we used (a) intraclass
      correlation coefficients (ICC) with the variance between CMSs as signal and the
      variance between raters, the variance within raters, and the signal as noise; (b)
      scatter plots; and (c) Bland-Altman plots. RESULTS: ICCs were 0.47 for the FT and
      0.37 for the SG. Scatter and Bland-Altman plots showed large between- and within
      person variability; 64.2% and 11.3% of the CMSs ratings were in the correct order
      on both occasions on the FT and SG, respectively. CONCLUSION: Our results suggest
      moderate reliability of CMSs ratings for the FT and poor reliability for the SG,
      which may explain their lack of improving the SG's measurement properties.
      Investigators should use appropriate reliability statistics when addressing
      related issues.

PMID- 15845333
TI  - Reliability and validity of the PORPUS, a combined psychometric and utility-based
      quality-of-life instrument for prostate cancer.
AB  - BACKGROUND: Although utility-based quality-of-life instruments are often used in
      economic evaluations and psychometric instruments in treatment evaluations, these
      are complementary approaches to assessing outcomes. In this study we developed
      and tested these two forms of quality-of-life instruments, both based on a
      single, validated, health classification system. OBJECTIVES: To assess the
      measurement properties (reliability and validity) of two newly developed
      psychometric and utility-based instruments for assessing outcomes associated with
      prostate cancer. METHODS: 141 men with cancer of the prostate (CaP), treated with
      radical prostatectomy, radiation therapy, hormonal therapy, and/or chemotherapy
      were assessed with both instruments and other standard psychometric and utility
      based instruments. RESULTS: Analyses indicate the test instruments are reliable
      and valid. Full-scale correlations between the instruments and standard
      instruments indicate validity, as do correlations of key subscales, and an
      evaluation of linear associations with the UCLA-Prostate Cancer Symptom Scales.
      CONCLUSION: Evidence from this study supports the reliability and construct
      validity of the tested instruments. Prostate cancer outcomes can now be assessed
      by a combination of psychometric and utility-based methods, allowing a ready
      comparison of derived outcomes.

PMID- 15845334
TI  - Substantial effective sample sizes were required for external validation studies
      of predictive logistic regression models.
AB  - BACKGROUND AND OBJECTIVES: The performance of a prediction model is usually worse
      in external validation data compared to the development data. We aimed to
      determine at which effective sample sizes (i.e., number of events) relevant
      differences in model performance can be detected with adequate power. METHODS: We
      used a logistic regression model to predict the probability that residual masses
      of patients treated for metastatic testicular cancer contained only benign
      tissue. We performed standard power calculations and Monte Carlo simulations to
      estimate the numbers of events that are required to detect several types of model
      invalidity with 80% power at the 5% significance level. RESULTS: A validation
      sample with 111 events was required to detect that a model predicted too high
      probabilities, when predictions were on average 1.5 times too high on the odds
      scale. A decrease in discriminative ability of the model, indicated by a decrease
      in the c-statistic from 0.83 to 0.73, required 81 to 106 events, depending on the
      specific scenario. CONCLUSION: We suggest a minimum of 100 events and 100
      nonevents for external validation samples. Specific hypotheses may, however,
      require substantially higher effective sample sizes to obtain adequate power.

PMID- 15845335
TI  - Nondisease factors affected trajectories of disability in a prospective study.
AB  - OBJECTIVE: To examine nondisease factors, including sociodemographic variables,
      health behaviors and psychosocial factors as determinants of trajectories of
      disability. STUDY DESIGN AND SETTING: We used a classification of 10 trajectories
      of disability based on a multiround prospective study design; nine trajectories
      grouped survivors with a similar level and time course of disability, one
      included all deaths. Multinomial logistic regression was used to assess
      associations between these trajectories and a wide range of nondisease factors.
      RESULTS: Correcting for age, sex, and four chronic diseases, we found that
      sociodemographic factors (education and income), health behaviors (leisure-time
      physical activity and BMI), and psychosocial factors (locus of control,
      neuroticism, and active problem focusing) were significantly associated with the
      trajectories of disability. Moreover, our results pointed to factors associated
      with disability trajectories that were characterized by sudden increase (external
      locus of control and, to a lesser extent, BMI), strong fluctuations (neuroticism,
      BMI, external locus of control), or high severity (leisure-time physical
      inactivity) of disability. CONCLUSION: A wide range of nondisease factors is
      associated with the trajectories of disability. Preventing obesity, developing a
      more internal locus of control, and increasing physical activity could contribute
      to preventing trajectories characterized by rapid decline, large fluctuations or
      severe disability. Understanding the role of these factors should receive high
      priority.

PMID- 15845336
TI  - A difference in perception of quality of life in chronically ill children was
      found between parents and pediatricians.
AB  - BACKGROUND AND OBJECTIVES: Quality of life measurements can help to estimate the
      well-being of chronically ill patients, and disclose discrepancies in perception
      between physicians and patients that might otherwise interfere with the
      effectiveness of treatment. The objective was to investigate the differences in
      perception of quality of life between parents of chronically ill children and
      pediatricians. METHODS: A cross-sectional study was conducted in four tertiary
      pediatric care centers in The Netherlands. The Health Utilities Index mark 3
      (HUI3) was used by 37 pediatricians and 279 parents of patients (children aged 1
      to 17 years) with cystic fibrosis admitted either in daycare or for a pneumonia,
      or patients with newly diagnosed acute lymphoblastic leukemia, juvenile
      idiopathic arthritis, or asthma. RESULTS: Differences in perception of quality of
      life between parents and pediatricians appeared to be dependent of the disease.
      In patients with acute lymphoblastic leukemia (OR 7.4; [95% CI 2.88-18.97],
      juvenile idiopathic arthritis (4.7; [95% CI 2.00-11.22]), and asthma (2.3; [95%
      CI 1.13-4.69]) a difference in perception was more likely to occur than in
      patients with cystic fibrosis admitted in daycare. CONCLUSION: At the onset of a
      chronic disease, the parents of pediatric patients may be misunderstood by health
      care professionals, especially in subjective attributes. Assessment of quality of
      life may contribute to better understanding between pediatricians and parents,
      and thus may even enhance compliance and treatment effects.

PMID- 15845337
TI  - A multivariate regression model predicted falls in residents living in
      intermediate hostel care.
AB  - BACKGROUND AND OBJECTIVE: To evaluate whether individual falls risk could be
      predicted in a frail elderly population. STUDY DESIGN AND SETTING: We developed
      and tested an assessment tool and falls risk score for predicting falls based on
      a multivariate regression model in a prospective cohort study of intermediate
      care residents. RESULTS: During the follow-up period, 1,736 falls by 1,107
      subjects were recorded with an average of 170 falls per 100 person-years. Fifty
      percent of the study population had at least one fall within a year. Significant
      independent risk factors were poor balance, cognitive impairment, incontinence,
      higher illness severity rating, and older age. Twenty-two percent of participants
      with a falls risk score > or =7 accounted for 42% of the total falls, with a
      falls rate of 317 per 100 person-years. This rate was a sixfold increase from the
      falls rate of 52 per 100 person-years observed in participants with a score < 3.
      A high score (> or =7) indicated almost a 2 in 3 chance of falling, while a low
      score (<3) indicated approximately a 1 in 7 chance of falling within 6 months.
      CONCLUSION: The assessment tool and falls risk score could identify individuals
      in this frail elderly population at high risk of falls.

PMID- 15845338
TI  - A cohort study found good respiratory, sensory and motor functions decreased
      mortality risk in older people.
AB  - BACKGROUND AND OBJECTIVE: The main aims of this study were to evaluate the
      separate and joint effects of respiratory, sensory, and psychomotor function,
      muscle strength, and mobility in predicting mortality in older men and women, and
      to find a way to control multicollinearity in a multivariate Cox regression
      model. METHODS: Mortality was followed for 10 years (1990-2000) in an entire
      cohort of 75-year-old residents of the city of Jyvaskyla, Finland (born in 1914;
      N=388). Cox regression models and principal component estimation were employed to
      study the association between the covariates and mortality. RESULTS: The study
      indicated that, after adjustment for fatal diseases and cognitive capacity, vital
      capacity, tapping rate, muscle strength, and walking speed predict mortality in
      elderly men and women to a similar extent. The hazard ratio for mortality for
      those in the lowest tertile of the principal component representing all the
      significant physiological functions was from three to four times higher than for
      those in the highest tertile. CONCLUSION: Our results suggest that a poor level
      in any of the measured functions has a similar impact on the risk for mortality,
      which is further increased by combining the different results. No single,
      dominant predictor of mortality emerged.

PMID- 15845339
TI  - Health problems lead to considerable productivity loss at work among workers with
      high physical load jobs.
AB  - OBJECTIVE: To assess the feasibility and validity of two instruments for the
      measurement of health-related productivity loss at work. STUDY DESIGN AND
      SETTING: A cross-sectional study was conducted in two occupational populations
      with a high prevalence of health problems: industrial workers (n=388) and
      construction workers (n=182). We collected information on self-reported
      productivity during the previous 2 weeks and during the last work day with the
      Health and Labor Questionnaire (HLQ) and the Quantity and Quality instrument
      (QQ), with added data on job characteristics, general health, presence of
      musculoskeletal complaints, sick leave, and health-care consumption. For
      construction workers, we validated self-reported productivity with objective
      information on daily work output from 19 work site observations. RESULTS: About
      half the workers with health problems on the last working day reported reduced
      work productivity (QQ), or 10.7% of all industrial workers and 11.8% of all
      construction workers, resulting in a mean loss of 2.0 hr/day per worker with
      reduced work productivity. The proportion of workers with reduced productivity
      was significantly lower on the HLQ: 5.3% of industrial workers and 6.5% of
      construction workers. Reduced work productivity on the HLQ and the QQ was
      significantly associated with musculoskeletal complaints, worse physical, mental
      and general health, and recent absenteeism. The QQ and HLQ questionnaires
      demonstrated poor agreement on the reporting of reduced productivity. Self
      reported productivity on the QQ correlated significantly with objective work
      output (r=.48). CONCLUSION: Health problems may lead to considerable sickness
      presenteeism. The QQ measurement instrument is better understandable, and more
      feasible for jobs with low opportunities for catching up on backlogs.

PMID- 15845340
TI  - Pain and pain treatment were associated with traffic accident involvement in a
      cohort of middle-aged workers.
AB  - BACKGROUND AND OBJECTIVE: To assess the influence of medical conditions on road
      traffic accidents among a cohort of middle-aged workers and pensioners. STUDY
      DESIGN AND SETTING: A longitudinal study of 13,548 participants from a cohort
      study of French workers. Follow-up data covered the 1989-2000 period. Adjusted
      hazards ratios (HR(adj)) for serious accidents were computed by Cox's
      proportional hazards regression with time-dependent covariates adjusted for age,
      occupation, annual mileage in 2001, alcohol consumption, and number of reported
      health problems. RESULTS: Men who reported treated dental or gingival problems
      (HR(adj)=8.57, 95% confidence interval CI=2.70-27.2) and women who reported
      treated renal colic or kidney stones (HR(adj)=9.71, 95% CI=2.40-39.3) were much
      more likely to have a serious traffic accident. Treated glaucoma, hiatal hernia
      or gastric ulcers, and diabetes among women and treated cataract among men were
      also found to be associated with the risk of serious traffic accidents.
      CONCLUSIONS: This study raises the hypothesis that pain and pain treatment
      (singly or in combination) could increase the risk of road traffic accident and
      confirms that medical conditions traditionally found to be associated with
      traffic accident involvement of older drivers are also risk factors for middle
      aged drivers.

PMID- 15845341
TI  - Longitudinal changes in patient vs. physician-based outcome measures did not
      significantly correlate in asthma.
AB  - BACKGROUND AND OBJECTIVE: Although improving health status is one important aim
      in managing asthmatic patients, few studies have evaluated their health status
      longitudinally. Therefore, we examined longitudinal changes in health status of
      asthma patients, and compared them with changes in physiological measures.
      METHODS: Eighty-seven outpatients with stable asthma after 6 months of treatment
      were recruited. Health status using the Asthma Quality of Life Questionnaire
      (AQLQ) and the St. George's Respiratory Questionnaire (SGRQ), pulmonary function,
      peak expiratory flow (PEF) values, and airway hyperresponsiveness (AHR) were
      evaluated at entry and every year over a 5-year period. RESULTS: Using mixed
      effects models to estimate the slopes, the overall AQLQ score declined
      statistically at a mean rate of 0.06 units/year (P=.0091). However, this decline
      did not reach a clinically significant level at 5 years. The total SGRQ score did
      not change significantly (P=.54). Although the forced expiratory volume in 1 sec
      declined at a mean rate of 53 mL/year, the PEF variability and AHR improved
      significantly. CONCLUSION: Health status was clinically stable over the 5-year
      study period in patients with asthma, which contrasted with the changes in the
      physiological outcome measures. As a patient centered outcome measure, health
      status should be followed separately.

PMID- 15845342
TI  - "Residual change" analysis is not equivalent to analysis of covariance.

PMID- 15845344
TI  - Circadian clocks, clock networks, arylalkylamine N-acetyltransferase, and
      melatonin in the retina.
AB  - Circadian clocks are self-sustaining genetically based molecular machines that
      impose approximately 24h rhythmicity on physiology and behavior that synchronize
      these functions with the solar day-night cycle. Circadian clocks in the
      vertebrate retina optimize retinal function by driving rhythms in gene
      expression, photoreceptor outer segment membrane turnover, and visual
      sensitivity. This review focuses on recent progress in understanding how clocks
      and light control arylalkylamine N-acetyltransferase (AANAT), which is thought to
      drive the daily rhythm in melatonin production in those retinas that synthesize
      the neurohormone; AANAT is also thought to detoxify arylalkylamines through N
      acetylation. The review will cover evidence that cAMP is a major output of the
      circadian clock in photoreceptor cells; and recent advances indicating that
      clocks and clock networks occur in multiple cell types of the retina.

PMID- 15845345
TI  - Control of programmed cell death by neurotransmitters and neuropeptides in the
      developing mammalian retina.
AB  - It has long been known that a barrage of signals from neighboring and connecting
      cells, as well as components of the extracellular matrix, control cell survival.
      Given the extensive repertoire of retinal neurotransmitters, neuromodulators and
      neurotrophic factors, and the exhuberant interconnectivity of retinal
      interneurons, it is likely that various classes of released neuroactive
      substances may be involved in the control of sensitivity to retinal cell death.
      The aim of this article is to review evidence that neurotransmitters and
      neuropeptides control the sensitivity to programmed cell death in the developing
      retina. Whereas the best understood mechanism of execution of cell death is that
      of caspase-mediated apoptosis, current evidence shows that not only there are
      many parallel pathways to apoptotic cell death, but non-apoptotic programs of
      execution of cell death are also available, and may be triggered either in
      isolation or combined with apoptosis. The experimental data show that many
      upstream signaling pathways can modulate cell death, including those dependent on
      the second messengers cAMP-PKA, calcium and nitric oxide. Evidence for
      anterograde neurotrophic control is provided by a variety of models of the
      central nervous system, and the data reviewed here indicate that an early
      function of certain neurotransmitters, such as glutamate and dopamine, as well as
      neuropeptides such as pituitary adenylyl cyclase-activating polypeptide and
      vasoactive intestinal peptide is the trophic support of cell populations in the
      developing retina. This may have implications both regarding the mechanisms of
      retinal organogenesis, as well as pathological conditions leading to retinal
      dystrophies and to dysfunctional cellular behavior.

PMID- 15845346
TI  - Prevalent misconceptions about acute retinal vascular occlusive disorders.
AB  - Acute retinal vascular occlusive disorders collectively constitute one of the
      major causes of blindness or seriously impaired vision, and yet there is marked
      controversy on their pathogeneses, clinical features and particularly their
      management. This is because the subject is plagued by multiple misconceptions.
      These include that: (i) various acute retinal vascular occlusions represent a
      single disease; (ii) estimation of visual acuity alone provides all the
      information necessary to evaluate visual function; (iii) retinal venous
      occlusions are a single clinical entity; (iv) retinal vein occlusion is
      essentially a disease of the elderly and is not seen in the young; (v) central
      retinal vein occlusion (CRVO) is one disease; (vi) fluorescein fundus angiography
      is the best test to differentiate ischemic from nonischemic CRVO; (vii) the site
      of occlusion in CRVO is invariably at the lamina cribrosa; (viii) clinical
      picture of CRVO is often due to compression or strangulation of the central
      retinal vein (CRV) in the lamina cribrosa and not its occlusion; (ix) an eye can
      develop both CRVO and central retinal artery occlusion (CRAO) simultaneously; (x)
      every eye with CRVO is at risk of developing neovascular glaucoma; (xi) lowering
      intraocular pressure (IOP) helps to improve retinal circulation in an eye with
      CRVO; (xii) every patient with retinal vein occlusion should have complete
      hematologic and coagulation evaluation; (xiii) the natural history of CRVO does
      not usually involve spontaneous visual improvement; (xiv) management of CRVO is
      similar to that of venous thrombosis anywhere else in the body, i.e. with aspirin
      and/or anti-coagulants; (xv) fibrinolytic agents can dissolve an organized
      thrombus in the CRV; (xvi) it is beneficial to lower blood pressure in patients
      with CRVO; (xvii) panretinal photocoagulation used in ischemic retinal venous
      occlusive disorders has no deleterious side-effects; (xviii) glaucoma or ocular
      hypertension can cause branch retinal vein occlusion; (xix) branch retinal vein
      occlusion can cause neovascular glaucoma; (xx) in eyes with CRAO, the artery is
      usually not completely occluded; (xxi) CRAO is always either embolic or
      thrombotic in origin; (xxii) amaurosis fugax is always due to retinal ischemia
      secondary to transient retinal arterial embolism; (xxiii) asymptomatic plaque(s)
      in retinal arteries do not require a detailed evaluation; (xxiv) retinal function
      can improve even when acute retinal ischemia due to CRAO has lasted for 20h or
      more; (xxv) CRAO, like ischemic CRVO, can result in development of ocular
      neovascularization; (xxvi) panretinal photocoagulation is needed for "disc
      neovascularization" in CRAO; (xxvii) fibrinolytic agents are the treatment of
      choice in CRAO; (xxviii) there is no chance of an eye with retinal arterial
      occlusion having spontaneous visual improvement; (xxix) absence of any
      abnormality on Doppler evaluation of the carotid artery or echography of the
      heart always rules out those sites as the source of embolism; and (xxx) absence
      of an embolus in the retinal artery means the occlusion was not caused by an
      embolus. The major cause of all these misconceptions is the lack of a proper
      understanding of basic scientific facts related to the various diseases. The
      objective of this paper is to discuss these misconceptions, based on these
      scientific facts, to clarify the understanding of these blinding disorders, and
      to place their management on a rational, scientific basis.

PMID- 15845347
TI  - Adaptive plasticity during the development of colour vision.
AB  - Colour vision greatly enhances the discriminatory and cognitive capabilities of
      visual systems and is found in a great majority of vertebrates and many
      invertebrates. However, colour coding visual systems are confronted with the fact
      that the external stimuli are ambiguous because they are subject to constant
      variations of luminance and spectral composition. Furthermore, the transmittance
      of the ocular media, the spectral sensitivity of visual pigments and the ratio of
      spectral cone types are also variable. This results in a situation where there is
      no fixed relationship between a stimulus and a colour percept. Colour constancy
      has been identified as a powerful mechanism to deal with this set of problems;
      however, it is active only in a short-term time range. Changes covering longer
      periods of time require additional tuning mechanisms at the photoreceptor level
      or at postreceptoral stages of chromatic processing. We have used the
      trichromatic blue acara (Aequidens pulcher, Cichlidae) as a model system and
      studied retinal morphology and physiology, and visually evoked behaviour after
      rearing fish for 1-2 years under various conditions including near monochromatic
      lights (spectral deprivation) and two intensities of white light (controls). In
      general, long-term exposure to long wavelengths light had lesser effects than
      light of middle and short wavelengths. Within the cone photoreceptors, spectral
      deprivation did not change the absorption characteristics of the visual pigments.
      By contrast, the outer segment length of middle and long-wave-sensitive cones was
      markedly increased in the blue rearing group. Furthermore, in the same group, we
      observed a loss of 65% short-wave-sensitive cones after 2 years. These changes
      may be interpreted as manifestations of compensatory mechanisms aimed at
      restoring the balance between the chromatic channels. At the horizontal cell
      level, the connectivity between short-wave-sensitive cones and the H2 cone
      horizontal cells, and the spinule dynamics were both affected in the blue light
      group. This observation rules out the role of spinules as sites of chromatic
      feedback synapses. The light-evoked responses of H2 horizontal cells were also
      sensitive to spectral deprivation showing a shift of the neutral point towards
      short wavelengths in the blue rearing group. Interestingly, we also found an
      intensity effect because in the group reared in bright white light the neutral
      point was more towards longer wavelength than in the dim light group. Like the
      changes in the cones, the reactions of horizontal cells to spectral deprivation
      in the long wave domain can be characterised as compensatory. We also tested the
      spectral sensitivity of the various experimental groups of blue acara in visually
      evoked behaviour using the optomotor response paradigm. In this case, the changes
      in the relative spectral sensitivity were more complex and could not be explained
      by a simple extrapolation of the adaptive and compensatory processes in the outer
      retina. We conclude that the inner retina, and/or the optic tectum are also
      involved and react to the changes of the spectral environment. In summary, we
      have shown a considerable developmental plasticity in the colour vision system of
      the blue acara, where epigenetic adaptive processes at various levels of the
      visual system respond to the specific spectral composition of the surroundings
      and provide a powerful mechanism to ensure functional colour vision in different
      visual environments. We suggest that processes involving an active fine-tuning of
      the photoreceptors and the postreceptoral processing of chromatic information
      during ontogenetic development are a general feature of all colour vision
      systems. Such mechanisms would establish a functional balance between the various
      chromatic channels. This appears to be an essential condition for the cognitive
      systems to extract the relevant and stable information from the unstable and
      changing stimulus situation.

PMID- 15845348
TI  - Fitness of drug-resistant malaria parasites.
AB  - Drug-resistant mutant forms of an organism are likely to be less fit than their
      wild-type strains in the absence of selection. Experimental work on prokaryotic
      organisms suggests that this is the case, but that compensatory mutations may
      occur which restore the fitness of mutants to that of sensitive forms. Here, we
      review experimental and field studies on this subject in malaria. In the rodent
      model Plasmodium chabaudi, a pyrimethamine-resistant mutant has been found to
      grow more slowly in mice than its drug-sensitive progenitor; however, following
      passage in the absence of the drug it grew faster, suggesting the occurrence of
      compensatory mutations. Similar findings were made with a chloroquine-resistant
      mutant. Field studies on Plasmodium falciparum have provided circumstantial
      evidence of a loss of fitness of chloroquine-resistant mutants, which appear to
      become less frequent in the parasite population following withdrawal of the drug.
      However, the occurrence of frequent recombination in the life-cycle of this
      parasite means that in natural conditions, a gene conferring resistance, once it
      has arisen, can then spread into a diversity of genetically distinct backgrounds
      which will influence its fitness and capacity to survive in the parasite
      population.

PMID- 15845350
TI  - Src kinase regulation by phosphorylation and dephosphorylation.
AB  - Src and Src-family protein-tyrosine kinases are regulatory proteins that play key
      roles in cell differentiation, motility, proliferation, and survival. The
      initially described phosphorylation sites of Src include an activating
      phosphotyrosine 416 that results from autophosphorylation, and an inhibiting
      phosphotyrosine 527 that results from phosphorylation by C-terminal Src kinase
      (Csk) and Csk homologous kinase. Dephosphorylation of phosphotyrosine 527
      increases Src kinase activity. Candidate phosphotyrosine 527 phosphatases include
      cytoplasmic PTP1B, Shp1 and Shp2, and transmembrane enzymes include CD45,
      PTPalpha, PTPepsilon, and PTPlambda. Dephosphorylation of phosphotyrosine 416
      decreases Src kinase activity. Thus far PTP-BL, the mouse homologue of human PTP
      BAS, has been shown to dephosphorylate phosphotyrosine 416 in a regulatory
      fashion. The platelet-derived growth factor receptor protein-tyrosine kinase
      mediates the phosphorylation of Src Tyr138; this phosphorylation has no direct
      effect on Src kinase activity. The platelet-derived growth factor receptor and
      the ErbB2/HER2 growth factor receptor protein-tyrosine kinases mediate the
      phosphorylation of Src Tyr213 and activation of Src kinase activity. Src kinase
      is also a substrate for protein-serine/threonine kinases including protein kinase
      C (Ser12), protein kinase A (Ser17), and CDK1/cdc2 (Thr34, Thr46, and Ser72). Of
      the three protein-serine/threonine kinases, only phosphorylation by CDK1/cdc2 has
      been demonstrated to increase Src kinase activity. Although considerable
      information on the phosphoprotein phosphatases that catalyze the hydrolysis of
      Src phosphotyrosine 527 is at hand, the nature of the phosphatases that mediate
      the hydrolysis of phosphotyrosine 138 and 213, and phosphoserine and
      phosphothreonine residues has not been determined.

PMID- 15845349
TI  - Exploring the folate pathway in Plasmodium falciparum.
AB  - As in centuries past, the main weapon against human malaria infections continues
      to be intervention with drugs, despite the widespread and increasing frequency of
      parasite populations that are resistant to one or more of the available
      compounds. This is a particular problem with the lethal species of parasite,
      Plasmodium falciparum, which claims some two million lives per year as well as
      causing enormous social and economic problems. Amongst the antimalarial drugs
      currently in clinical use, the antifolates have the best defined molecular
      targets, namely the enzymes dihydrofolate reductase (DHFR) and dihydropteroate
      synthase (DHPS), which function in the folate metabolic pathway. The products of
      this pathway, reduced folate cofactors, are essential for DNA synthesis and the
      metabolism of certain amino acids. Moreover, their formation and interconversions
      involve a number of other enzymes that have not as yet been exploited as drug
      targets. Antifolates are of major importance as they currently represent the only
      inexpensive regime for combating chloroquine-resistant malaria, and are now first
      line drugs in a number of African countries. Aspects of our understanding of this
      pathway and antifolate drug resistance are reviewed here, with a particular
      emphasis on approaches to analysing the details of, and balance between, folate
      biosynthesis by the parasite and salvage of pre-formed folate from exogenous
      sources.

PMID- 15845351
TI  - Impaired insulin-signaling in hypertrophied hearts contributes to ischemic
      injury.
AB  - Despite increased glucose utilization by hypertrophied myocardium, these hearts
      exhibit a slower rate of glucose uptake (GU). We hypothesized that, in
      hypertrophied myocardium, a defect of the insulin-responsive glucose transporter
      is responsible for impaired GU and metabolism during ischemia, contributing to
      post-ischemic myocardial dysfunction. In a rabbit model of pressure-overload
      hypertrophy, GU ((31)P NMR spectroscopy) and total/phosphorylated insulin
      signaling intermediates were assayed: insulin-receptor, insulin-receptor
      substrate-1 (IRS-1), phosphatidylinositol-3-kinase (PI3-k), GLUT-4 translocation
      and contractile function in an isolated heart ischemia/reperfusion model. Total
      protein was not different between hypertrophied and control hearts.
      Phosphorylation of IRS-1 and PI3-k activity was significantly lower in
      hypertrophy during ischemia. GU was impaired pre-ischemia in hypertrophy,
      remained lower during early reperfusion, and was associated with impaired
      recovery of contractile function. In conclusion, a defect in IRS-1
      phosphorylation and PI3-k activation in hypertrophied hearts restricts insulin
      mediated GLUT-4 translocation and ischemia, a known stimulus of GLUT-4
      translocation, does not compensate for this defect.

PMID- 15845352
TI  - Identification of Zfp-57 as a downstream molecule of STAT3 and Oct-3/4 in
      embryonic stem cells.
AB  - Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass
      of blastocysts. Transcription factor STAT3 is essential for the self-renewal of
      ES cells. In this study, we searched for downstream molecules of STAT3 in ES
      cells. Using DNA chip analysis, we obtained zinc finger protein (Zfp)-57. The
      expression of Zfp-57 was restricted to undifferentiated ES cells and activation
      of STAT3 led to expression of Zfp-57. We also found that forced expression of a
      dominant-negative mutant of STAT3 or repression of Oct-3/4 expression led to down
      regulation of Zfp-57. Targeted disruption of Zfp-57 resulted in no gross
      phenotypical defects, including expression of undifferentiated-state-specific
      genes. These data suggest that Zfp-57 is a downstream molecule of STAT3 and Oct
      3/4 in ES cells, although dispensable for their self-renewal.

PMID- 15845353
TI  - The role of bone marrow-derived cells in bone fracture repair in a green
      fluorescent protein chimeric mouse model.
AB  - We investigated the role of bone marrow cells in bone fracture repair using green
      fluorescent protein (GFP) chimeric model mice. First, the chimeric model mice
      were created: bone marrow cells from GFP-transgenic C57BL/6 mice were injected
      into the tail veins of recipient wild-type C57BL/6 mice that had been irradiated
      with a lethal dose of 10Gy from a cesium source. Next, bone fracture models were
      created from these mice: closed transverse fractures of the left femur were
      produced using a specially designed device. One, three, and five weeks later,
      fracture lesions were extirpated for histological and immunohistochemical
      analyses. In the specimens collected 3 and 5 weeks after operation, we confirmed
      calluses showing intramembranous ossification peripheral to the fracture site.
      The calluses consisted of GFP- and osteocalcin-positive cells at the same site,
      although the femur consisted of only osteocalcin-positive cells. We suggest that
      bone marrow cells migrated outside of the bone marrow and differentiated into
      osteoblasts to make up the calluses.

PMID- 15845354
TI  - Subcellular localization of human neutral ceramidase expressed in HEK293 cells.
AB  - We previously reported that rat and mouse neutral ceramidases were mainly
      localized to plasma membranes as a type II integral membrane protein and partly
      detached from the cells via processing of the N-terminal/anchor sequence when
      expressed in HEK293 cells [M. Tani, H. Iida, M. Ito, O-glycosylation of mucin
      like domain retains the neutral ceramidase on the plasma membranes as a type II
      integral membrane protein, J. Biol. Chem. 278 (2003) 10523-10530]. In contrast,
      the human homologue was exclusively detected in mitochondria when expressed in
      HEK293 and MCF7 cells as a fusion protein with green fluorescent protein at the N
      terminal of the enzyme [S.E. Bawab, P. Roddy, T. Quian, A. Bielawska, J.J.
      Lemasters, Y.A. Hannun, Molecular cloning and characterization of a human
      mitochondrial ceramidase, J. Biol. Chem. 275 (2000) 21508-21513]. Given this
      discrepancy, we decided to clone the neutral ceramidase from human kidney cDNA
      and re-examine the intracellular localization of the enzyme when expressed in
      HEK293 cells. The putative amino acid sequence of the newly cloned enzyme was
      identical to that reported for human neutral ceramidase except at the N-terminal;
      the new protein was 19 amino acids longer at the N-terminal. We found that the
      putative full-length human neutral ceramidase was transported to plasma
      membranes, but not to mitochondria, possibly via a classical ER/Golgi pathway and
      localized mainly in plasma membranes when expressed in HEK293 cells. The N
      terminal-truncated mutant, previously reported as a human mitochondrial
      ceramidase, was also weakly expressed in HEK293 cells but mainly released into
      the medium possibly due to the insufficient signal/anchor sequence.

PMID- 15845355
TI  - Effect of thymosin beta15 on the branching of developing neurons.
AB  - The thymosin betas (Tbetas) are polypeptide regulators of actin dynamics that are
      critical for the growth and branching of neurites in developing neurons. We found
      that mRNAs for Tbeta4, Tbeta10, and Tbeta15 were highly expressed in the
      developing rat brain during neuritogenesis, supporting a role for the Tbetas in
      this process. Overexpression of the Tbetas increased the number of neurite
      branches per neuron in cultured hippocampal and cerebral cortex neurons, and
      Tbeta15 had the greatest effect. Actin binding activity appears to be essential
      for the branch-promoting activity of Tbetas because two mutants of Tbeta15
      lacking monomeric actin binding activity failed to stimulate branch formation. We
      also found that transfection of siRNA against Tbeta15 reduced branching. Taken
      together, these data suggest that the three Tbetas, and especially Tbeta15,
      stimulate neurite branching during brain development.

PMID- 15845356
TI  - MAP1B phosphorylation is differentially regulated by Cdk5/p35, Cdk5/p25, and JNK.
AB  - Mode I phosphorylated MAP1B is observed in developing and pathogenic brains.
      Although Cdk5 has been believed to phosphorylate MAP1B in the developing cerebral
      cortex, we show that a Cdk5 inhibitor does not suppress mode I phosphorylation of
      MAP1B in primary and slice cultures, while a JNK inhibitor does. Coincidently, an
      increase in phosphorylated MAP1B was not observed in COS7 cells when Cdk5 was
      cotransfected with p35, but this did occur with p25 which is specifically
      produced in pathogenic brains. Our primary culture studies showed an involvement
      of Cdk5 in regulating microtubule dynamics without affecting MAP1B
      phosphorylation status. The importance of regulating microtubule dynamics in
      neuronal migration was also demonstrated by in utero electroporation experiments.
      These findings suggest that mode I phosphorylation of MAP1B is facilitated by JNK
      but not Cdk5/p35 in the developing cerebral cortex and by Cdk5/p25 in pathogenic
      brains, contributing to various biological events.

PMID- 15845357
TI  - Modeling the tertiary structure of human cathepsin-E.
AB  - Cathepsin-E is an endolysosomal aspartic proteinase and is predominantly
      expressed in immune system cells. Deficiency of cathepsin-E is associated with
      the development of atopic dermatitis, a pruritic inflammatory skin disease, which
      has put us to face a high selectivity challenge in the development of drugs for
      the therapy of Alzheimer's disease or breast cancer. This is because BACE1 (also
      known as beta-secretase) and cathepsin-D, both belonging to the family of
      aspartic proteinases, might interact with the same compound as cathepsin-E does.
      BACE1 is a putative prime therapeutic target for the treatment of Alzheimer's
      disease, and cathepsin-D a potential target for breast cancer. Accordingly, in
      the course of finding drugs against Alzheimer's disease or breast cancer by
      inhibiting BACE1 or cathepsin-D, the desired drugs should selectively inhibit
      only BACE1 or cathepsin-D, but definitely not cathepsin-E. To realize this, it is
      indispensable to find out the structural difference of the three enzymes. Since
      the crystal structures of BACE1 and cathepsin-D are already known, the lack of
      three-dimensional structure of cathepsin-E has become the bottleneck in this
      regard. In view of this, the three-dimensional structure of cathepsin-E has been
      developed. Although the overall structures of the three enzymes are quite similar
      to each other, some subtle difference around their active sites that
      distinguishes cathepsin-E from cathepsin-D and BACE1 has been revealed through an
      analysis of hydrogen bond network and microenvironment. The computed three
      dimensional structure of cathepsin-E and the relevant findings might provide
      useful insights for designing inhibitors with the desired selectivity.

PMID- 15845358
TI  - ACAT1 deletion in murine macrophages associated with cytotoxicity and decreased
      expression of collagen type 3A1.
AB  - In contrast to some published studies of murine macrophages, we previously showed
      that ACAT inhibitors appeared to be anti-atherogenic in primary human macrophages
      in that they decreased foam cell formation without inducing cytotoxicity. Herein,
      we examined foam cell formation and cytotoxicity in murine ACAT1 knockout (KO)
      macrophages in an attempt to resolve the discrepancies. Elicited peritoneal
      macrophages from normal C57BL6 and ACAT1 KO mice were incubated with DMEM
      containing acetylated LDL (acLDL, 100 microg protein/ml) for 48h. Cells became
      cholesterol enriched and there were no differences in the total cholesterol mass.
      Esterified cholesterol mass was lower in ACAT1 KO foam cells compared to normal
      macrophages (p<0.04). Cytotoxicity, as measured by the cellular release of
      [(14)C]adenine from macrophages, was approximately 2-fold greater in ACAT1 KO
      macrophages as compared to normal macrophages (p<0.0001), and this was
      independent of cholesterol enrichment. cDNA microarray analysis showed that ACAT1
      KO macrophages expressed substantially less collagen type 3A1 (26-fold), which
      was confirmed by RT-PCR. Total collagen content was also significantly reduced
      (57%) in lung homogenates isolated from ACAT1 KO mice (p<0.02). Thus, ACAT1 KO
      macrophages show biochemical changes consistent with increased cytotoxicity and
      also a novel association with decreased expression of collagen type 3A1.

PMID- 15845359
TI  - Antiviral activity of ovotransferrin derived peptides.
AB  - Ovotransferrin and lactoferrin are iron-binding proteins with antiviral and
      antibacterial activities related to natural immunity, showing marked sequence and
      structural homologies. The antiviral activity of two hen ovotransferrin fragments
      DQKDEYELL (hOtrf(219-227)) and KDLLFK (hOtrf(269-301) and hOtrf(633-638)) towards
      Marek's disease virus infection of chicken embryo fibroblasts is reported here.
      These fragments have sequence homology with two bovine lactoferrin fragments with
      antiviral activity towards herpes simplex virus, suggesting that these fragments
      could have a role for the exploitation of the antiviral activity of the intact
      proteins towards herpes viruses. NMR analysis showed that these peptides,
      chemically synthetized, did not possess any favourite conformation in solution,
      indicating that both the aminoacid sequence and the conformation they display in
      the intact protein are essential for the antiviral activity.

PMID- 15845360
TI  - Rescue of ligand binding of a mutant IGF-I receptor by complementation.
AB  - The IGF-I receptor binds IGF-I with complex kinetics characterized by a
      curvilinear Scatchard plot, suggesting receptor heterogeneity and apparent
      negative cooperativity. To explore the molecular mechanisms underlying these
      properties, we have characterized the binding of a hybrid receptor formed from a
      wild-type receptor monomer and a mutant receptor monomer devoid of binding
      activity. Receptor hybrids were generated by transient co-transfection of cDNAs
      encoding wild-type and mutant receptors with unique epitope tags. Hybrid
      receptors were purified from transfected cells by sequential immuno-affinity
      chromatography and their ligand-binding properties were determined.
      Complementation produced a hybrid with near wild-type affinity. Dissociation
      studies demonstrated that the hybrid did not exhibit negative cooperativity.

PMID- 15845361
TI  - Induction of a SSAT isoform in response to hypoxia or iron deficiency and its
      protective effects on cell death.
AB  - Spermidine/spermine N(1)-acetyltransferase (SSAT) is the key enzyme with regard
      to the maintenance of intracellular polyamine levels. It is an inducible enzyme,
      which may participate in adaptive responses to environmental stress. However,
      little is known regarding its responses to oxygen or nutrient deficiencies. Using
      microarray assays, we discovered that SSAT was enhanced under both oxygen- and
      iron-deficient conditions. However, RT-PCR revealed that the SSAT mRNA was not
      induced; rather, an mRNA variant was newly expressed. In this variant, the
      splicing-in of 110 bases induces early termination, generating a truncated
      isoform which lacks catalytic motifs. The variant expression occurs in other
      cancer cells and was irrelevant to both hypoxia-inducible factor 1 and to the
      redox state. We attempted to determine its role, using stable cell-lines. The
      expressed isoform was found to promote cell survival under iron-deficient
      conditions and blocked the cleavage of poly(ADP-ribose) polymerase. This isoform
      may contribute to the progression of tumors of a more malignant phenotype under
      poor conditions and may constitute a potential target for anticancer therapy.

PMID- 15845362
TI  - Regulation of the pituitary tumor transforming gene by insulin-like-growth factor
      I and insulin differs between malignant and non-neoplastic astrocytes.
AB  - The reasons for overexpression of the oncogene pituitary tumor transforming gene
      (PTTG) in tumors are still not fully understood. A possible influence of the
      insulin-like growth factor I (Igf-I) may be of interest, since enhanced Igf-I
      signalling was reported in various human tumors. We examined the influence of Igf
      I and insulin on PTTG expression in human astrocytoma cells in comparison to
      proliferating non-neoplastic rat embryonal astrocytes. PTTG mRNA expression and
      protein levels were increased in malignant astrocytes treated with Igf-I or
      insulin, whereas in rat embryonic astrocytes PTTG expression and protein levels
      increased only when cells were exposed to Igf-I. Enhanced transcription did not
      occur after treatment with inhibitors of phosphoinositol-3-kinase (PI3K) and
      mitogen-activated protein kinase (MAPK), blocking the two basic signalling
      pathways of Igf-I and insulin. In addition to this transcriptional regulation,
      both kinases directly bind to PTTG, suggesting a second regulatory route by
      phosphorylation. However, the interaction of endogenous PTTG with MAPK and PI3K,
      as well as PTTG phosphorylation were independent from Igf-I or insulin. The
      latter results were also found in human testis, which contains high PTTG levels
      as well as in nonneoplastic astrocytes. This suggest, that PI3K and MAPK
      signalling is involved in PTTG regulation not only in malignant astrocytomas but
      also in non-tumorous cells.

PMID- 15845363
TI  - 5-Azacytidine suppresses RNA polymerase II recruitment to the SLPI gene.
AB  - Histone methylation is regarded as a stable modification important in the
      epigenetic regulation of gene expression. Transcriptionally active chromatin is
      methylated at H3-K4 whereas repressed chromatin is methylated at H3-K9. To
      investigate the role of histone methylation in an acute inflammatory response,
      A549 cells were treated with IL-1beta and/or the methylase inhibitor 5
      azacytidine (5-aza), and histone H3-K4 methylation levels and transcription of
      secretory leukocyte protease inhibitor (SLPI) were measured. IL-1beta stimulation
      enhanced histone H3-K4 tri-methylation across the SLPI coding region at 24h. In
      parallel, IL-1beta enhanced recruitment of RNA polymerase II to the SLPI gene. 5
      aza attenuated both H3-K4 tri-methylation and RNA polymerase II recruitment to a
      similar extent resulting in reduced SLPI mRNA and protein levels. These data
      suggest that in addition to epigenetic regulation of constitutive SLPI
      expression, H3-K4 tri-methylation may play a role in stimulated SLPI expression
      by modulating RNA polymerase II recruitment and subsequent gene transcription.

PMID- 15845364
TI  - Structural basis for the presence of a monoglucosylated oligosaccharide in mature
      glycoproteins.
AB  - Arylphorin is an insect hexameric storage protein. The structures of the
      oligosaccharides attached to this protein have recently been determined. However,
      their precise functions remain to be established. Proteolysis and MALDI MS
      studies disclose that the amino acid residues Asn196 and Asn344 are N
      glycosylated with Glc(1)Man(9)GlcNAc(2) and Man(5-6)GlcNAc(2) oligosaccharides,
      respectively. Interestingly, significant variations in the amounts of glycans
      involving Glc(1)Man(9)GlcNAc(2) are evident in arylphorins purified from larvae
      reared at different seasons. The data suggest that the metabolism of larvae and
      local protein structure contribute to glycan development. Three-dimensional model
      of the protein speculated that N-glycosidic linkage to Asn196 in the
      Glc(1)Man(9)GlcNAc(2) structure was buried inside the twofold axis of the
      hexamer, whereas oligosaccharide linkages to Asn344 were completely exposed to
      solvent. This finding is in agreement with previous biochemical data showing that
      limited Glc(1)Man(9)GlcNAc(2) was released by protein-N-glycosidase F under non
      denaturing conditions, in contrast to Man(5-6)GlcNAc(2) oligosaccharides.

PMID- 15845365
TI  - The hybrid enzymes from alpha-aspartyl dipeptidase and L-aspartase.
AB  - With combinative functionalities as well as the improved activity and stability,
      the novel hybrid enzymes (HEs) from the heterogeneous enzymes of alpha-aspartyl
      dipeptidase (PepE, monomer) and l-aspartase (l-AspA, tetramer) were constructed
      successfully by gene random deletion strategy. The wild-type hybrid enzyme (WHE)
      and the evolved hybrid enzyme (EHE) were selected, respectively, upon the
      phenotype and the enzyme activity. The relative activity of the WHE tested was
      about 110% of the wild-type PepE and 26% of the wild-type l-AspA, whilst the
      activity of EHE was about 340% of the PepE and 87% of the l-AspA. In comparison
      to its individual wild-type enzymes, the EHE exhibited an improved
      thermostability, when examined at the enzyme concentration of 10(-7)mol/L, but
      the WHE showed a reduced thermostability. The activity of the EHE was about 3
      fold compared to that of the WHE. The current results give a good example that
      the hybridization of enzymes could be attained between the monomer and multimer
      enzymes. In addition, they also indicate that construction hybrid enzyme from
      evolved enzymes is feasible.

PMID- 15845366
TI  - Luman is capable of binding and activating transcription from the unfolded
      protein response element.
AB  - Luman (or LZIP, CREB3) is a transcription factor with an endoplasmic reticulum
      (ER)-transmembrane domain. Due to its structural similarities with ATF6, it is
      thought that Luman might also be involved in cellular stress responses. Here we
      report that Luman can bind and activate transcription from the consensus unfolded
      protein response element (UPRE). Mutations that disrupted the binding of Luman to
      the UPREs impaired its ability to activate transcription from these sites.
      Overexpression of Luman stimulated transcription of EDEM, a downstream effector
      of the mammalian unfolded protein response involved in ER-associated degradation
      (ERAD). Unlike ATF6, however, Luman was not activated by proteolytic cleavage in
      response to endoplasmic reticulum stressors such as tunicamycin and thapsigargin.
      These results suggest that the activation of ERAD by Luman is likely through a
      pathway different from the common ER stress response, and that additional
      factor(s) are required for the activation of this Luman-mediated pathway.

PMID- 15845367
TI  - Macrophages overexpressing tartrate-resistant acid phosphatase show altered
      profile of free radical production and enhanced capacity of bacterial killing.
AB  - Activated macrophages and osteoclasts express high amounts of tartrate-resistant
      acid phosphatase (TRACP, acp5). TRACP has a binuclear iron center with a redox
      active iron that has been shown to catalyze the formation of reactive oxygen
      species (ROS) by Fenton's reaction. Previous studies suggest that ROS generated
      by TRACP may participate in degradation of endocytosed bone matrix products in
      resorbing osteoclasts and degradation of foreign compounds during antigen
      presentation in activated macrophages. Here we have compared free radical
      production in macrophages of TRACP overexpressing (TRACP+) and wild-type (WT)
      mice. TRACP overexpression increased both ROS levels and superoxide production.
      Nitric oxide production was increased in activated macrophages of WT mice, but
      not in TRACP+ mice. Macrophages from TRACP+ mice showed increased capacity of
      bacterial killing. Recombinant TRACP enzyme was capable of bacterial killing in
      the presence of hydrogen peroxide. These results suggest that TRACP has an
      important biological function in immune defense system.

PMID- 15845368
TI  - High production of methyl mercaptan by L-methionine-alpha-deamino-gamma
      mercaptomethane lyase from Treponema denticola.
AB  - Methyl mercaptan is derived from l-methionine by the action of l-methionine-alpha
      deamino-gamma-mercaptomethane lyase (METase) and is a major component of oral
      malodor. This compound is highly toxic and is thought to play an important role
      in periodontal disease. We found that Treponema denticola, a member of the
      subgingival biofilm at periodontal disease sites, produced a large amount of
      methyl mercaptan even at low concentration of l-methionine. METase activity in a
      cell-free extract from T. denticola was detected by two-dimensional
      electrophoresis under non-denaturing conditions, and the protein spot that
      exhibited high METase activity was identified using a matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometer. The identified gene
      produced a METase with a K(m) value for l-methionine (0.55mM) that is much lower
      than those of METases previously identified in the other organisms. This result
      suggests that T. denticola is an important producer of methyl mercaptan in the
      subgingival biofilm.

PMID- 15845369
TI  - Phagocytic signaling molecules in lipid rafts of COS-1 cells transfected with
      FcgammaRIIA.
AB  - COS-1 cells bearing FcgammaRIIA were used as a model to demonstrate co
      localization of several enzymes previously shown to regulate neutrophil
      phagocytosis. In COS-1 cells, phospholipase D (PLD) in the membrane fraction was
      activated during phagocytosis. PLD was found almost exclusively in lipid rafts,
      along with RhoA and ARF1. Protein kinase C-delta (PKCdelta) and Raf-1
      translocated to lipid rafts. In neutrophils, ceramide levels increase during
      phagocytosis, indicating that FcgammaRIIA engagement initiates ceramide
      generation. Applying this model, we transfected COS-1 cells with FcgammaRIIA that
      had been mutated in the ITAM region, rendering them unable to ingest particles.
      When the mutant receptors were engaged, ceramide was generated and MAPK was
      activated normally, thus these processes did not require actual ingestion of
      particles. These results indicate that signaling proteins for phagocytosis are
      either constitutively present in, or are recruited to, lipid rafts where they are
      readily available to activate one another.

PMID- 15845370
TI  - Targeted disruption of inducible 6-phosphofructo-2-kinase results in embryonic
      lethality.
AB  - Inducible 6-phosphofructo-2-kinase (iPFK-2; PFKFB3) produces fructose-2,6
      bisphosphate (F2,6BP), which is a potent allosteric activator of 6-phosphofructo
      1-kinase (PFK-1), the rate-limiting step in glycolysis. iPFK-2 functions as an
      activator of anaerobic glycolysis within the hypoxic microenvironment of growing
      tumors. The early embryo is challenged similarly since the process of
      vasculogenesis does not begin until after embryonic day 7. We hypothesized that
      iPFK-2 expression is essential for the survival of the growing embryo. First, we
      cloned the mouse homolog of iPFK2 and found that it is abundantly expressed in
      cortical neurons, epithelial cells, and secretory cells of the choroid plexus,
      pancreas, and adrenal gland of the adult mouse. Using gene targeting, we then
      disrupted exons 3-7 of the mouse iPFK2 gene, which encode the substrate binding
      site. No full-term homozygous iPFK-2(-/-) progeny were produced from 11 F7 iPFK
      2(+/-) crosses and no homozygous iPFK-2(-/-) embryos were detected after 8 days
      of embryogenesis.

PMID- 15845371
TI  - Uroporphyria and hepatic carcinogenesis induced by polychlorinated biphenyls-iron
      interaction: absence in the Cyp1a2(-/-) knockout mouse.
AB  - Aryl hydrocarbon receptor ligands, such as polychlorinated biphenyls (PCBs),
      cause inhibition of the heme biosynthesis enzyme, uroporphyrinogen decarboxylase;
      this leads to uroporphyria and hepatic tumors, which are markedly enhanced by
      iron overload in C57BL/10 and C57BL/6 strains of mice. Cyp1a2(-/-) knockout mice
      were used to compare the effects of CYP1A2 expression on uroporphyria and liver
      carcinogenesis. PCBs in the diet (100ppm) of Cyp1a2(+/+) wild-type mice caused
      hepatic uroporphyria, which was strongly increased by iron-dextran (800mg Fe/kg).
      In contrast, uroporphyria was not detected in Cyp1a2(-/-) knockout mice, although
      expression of CYP1A1 and CYP2B10 was greatly induced. After 57 weeks on this
      diet, hepatic preneoplastic foci and tumors were seen in the Cyp1a2(+/+) mice;
      numbers and severity were enhanced by iron. No foci or tumors were detected in
      Cyp1a2(-/-) mice, although evidence for other forms of liver injury was observed.
      Our findings suggest a link not only between CYP1A2, iron metabolism, and the
      induction of uroporphyria by PCBs, but also with subsequent hepatocarcinogenesis.

PMID- 15845372
TI  - Identification of dynein light chain 2 as an interaction partner of p21-activated
      kinase 1.
AB  - p21-Activated kinase 1 (PAK1), a member of the evolutionarily conserved PAK
      family of serine/threonine kinases, is essential for a variety of cellular
      functions. Our previous studies showed that PAK1 participated in the apoptotic
      pathway mediated by p110C. To further investigate its functions, we used the
      yeast two-hybrid system to screen a human fetal brain cDNA library and identified
      dynein light chain 2 (DLC2)/myosin light chain (MLC) as an interacting partner of
      PAK1. The association of PAK1 with DLC2 was further confirmed by in vitro binding
      assay. With the stimulation of EGF, PAK1 interacted with HA-DLC2 in vivo and
      relocalized in cytoplasm near the perinuclear location in confocal microscope
      analysis. The deletion analysis showed that the interaction of DLC2 with PAK1
      occurred within the residues 210-332 of PAK1. For that studies showed that DLC2
      was a subunit of myosin complex, so it is possible that PAK1 binds to DLC2 and
      transports by myosin complex.

PMID- 15845373
TI  - Binding modes of dihydroquinoxalinones in a homology model of bradykinin receptor
      1.
AB  - We report the first homology model of human bradykinin receptor B1 generated from
      the crystal structure of bovine rhodopsin as a template. Using an automated
      docking procedure, two B1 receptor antagonists of the dihydroquinoxalinone
      structural class were docked into the receptor model. Site-directed mutagenesis
      data of the amino acid residues in TM1, TM3, TM6, and TM7 were incorporated to
      place the compounds in the binding site of the homology model of the human B1
      bradykinin receptor. The best pose in agreement with the mutation data was
      selected for detailed study of the receptor-antagonist interaction. To test the
      model, the calculated antagonist-receptor binding energy was correlated with the
      experimentally measured binding affinity (K(i)) for nine dihydroquinoxalinone
      analogs. The model was used to gain insight into the molecular mechanism for
      receptor function and to optimize the dihydroquinoxalinone analogs.

PMID- 15845374
TI  - DNA vector-based RNAi approach for stable depletion of poly(ADP-ribose)
      polymerase-1.
AB  - RNA-mediated interference (RNAi) is a powerful technique that is now being used
      in mammalian cells to specifically silence a gene. Some recent studies have used
      this technique to achieve variable extent of depletion of a nuclear enzyme
      poly(ADP-ribose) polymerase-1 (PARP-1). These studies reported either transient
      silencing of PARP-1 using double-stranded RNA or stable silencing of PARP-1 with
      a DNA vector which was introduced by a viral delivery system. In contrast, here
      we report that a simple RNAi approach which utilizes a pBS-U6-based DNA vector
      containing strategically selected PARP-1 targeting sequence, introduced in the
      cells by conventional CaPO(4) protocol, can be used to achieve stable and
      specific silencing of PARP-1 in different types of cells. We also provide a
      detailed strategy for selection and cloning of PARP-1-targeting sequences for the
      DNA vector, and demonstrate that this technique does not affect expression of its
      closest functional homolog PARP-2.

PMID- 15845375
TI  - Emergence of nuclear heparanase induces differentiation of human mammary cancer
      cells.
AB  - The study of epithelial differentiation touches upon many modern aspects of
      biology. The epithelium is in constant dialogue with the underlying mesenchyme to
      control stem cell activity, proliferation in transit-amplifying compartments,
      lineage commitment, terminal differentiation and, ultimately, cell death. There
      are spatially distinct compartments dedicated to each of these events. Recently
      we reported that heparanase is expressed in nucleus as well as in the cytoplasm
      and that nuclear heparanase seems to be related to cell differentiation. In this
      study, we investigated the role of nuclear heparanase in differentiation by
      transducing human mammary epithelial cancer cells with heparanase which was
      delivered specifically into nucleus. We observed that expression of nuclear
      heparanase allowed the cells to differentiate with the appearance of lipid
      droplets. This finding supports the idea that heparanase plays a novel role in
      epithelial cell differentiation apart from its known enzymatic function.

PMID- 15845376
TI  - Intracellular cAMP controls a physical association of V-1 with CapZ in cultured
      mammalian endocrine cells.
AB  - V-1, an ankyrin repeat protein with the activity to control tyrosine hydroxylase
      (TH) gene expression and transmitter release in PC12D cells, associates with
      CapZ, an actin capping protein, and thereby regulates actin polymerization in
      vitro. In this study, immunoprecipitation and Western blot analysis showed that V
      1 was physically associated with CapZ-beta in PC12D transfectants overexpressing
      V-1. These proteins were co-localized in the soma of Purkinje cells of rat
      cerebellum as assayed by immunohistochemistry. Furthermore, in the V-1
      transfectants, the amount of CapZ which physically associated with V-1 was
      steeply reduced at 2h after treatment with forskolin, but was thereafter
      increased to reach its initial level at 12h after forskolin-treatment. These
      results suggest that the association of V-1 with CapZ is controlled by a cAMP
      dependent signalling pathway probably to play a functional role in the regulatory
      mechanism of actin dynamics in the endocrine system and the central nervous
      system.

PMID- 15845377
TI  - PGE/cAMP and GM-CSF synergise to induce a pro-tolerance cytokine profile in
      monocytic cell lines.
AB  - This study demonstrates a synergistic action of prostaglandin E and GM-CSF which
      causes the release of pro-tolerant cytokines in two monocyte cell lines: U937 and
      ML-1. The prostaglandin effect is cyclic AMP dependent since stimulators of
      adenyl cyclase such as forskolin (fsk) can replace PGE. Fsk and GM-CSF
      combinations raised messenger RNA for IL-10, interleukin-1 receptor antagonist
      (IL-1ra), and CD14 as well as the released proteins. Effective levels of
      interleukin 12 are reduced. In these respects, the monocyte cells resemble the
      alternatively activated or tumour associated macrophages. A differential pattern
      in co-stimulatory molecule expression is seen; CD80 is unchanged but CD86 is
      markedly elevated and such a change is not seen in the alternatively activated
      macrophage but has been previously reported in monocytes resident in the non
      inflamed gut. Control of leukocyte responses by two agents acting in synergy
      could be effective in critical situations such as discrimination between
      pathogens and commensal bacteria, etc. Monocytes modified in such a way could
      provide a pro-tolerant environment (high IL-10, low IL-12) for antigen
      presentation by dendritic cells and thus may contribute to a normally permissive
      milieu, e.g., for food absorption.

PMID- 15845378
TI  - Expression profiles of mouse dendritic cell sarcoma are similar to those of
      hematopoietic stem cells or progenitors by clustering and principal component
      analyses.
AB  - We isolated and screened two tumor cell clones DD1 and DG6 with different
      capacity of metastasis from the same parent cell line, a mouse dendritic cell
      (DC) sarcoma, using limited dilution method. The genome-wide expressions of DD1
      and DG6 cells were detected by Affymetrix's MOE-430A microarray. The expression
      profiles related with mouse DC development were downloaded from GEO at NCBI and
      ArrayExpress at EBI database. In order to compare the expression of DC sarcoma
      and DC developmental arrays which was performed by MG-U74av2, we had screened the
      best matched probesets between MOE-430A and MG-U74av2 according to the probe
      identities from Affymetrix technical annotation. After the normalization of 11
      housekeeping genes across the 34 arrays (2 DC sarcoma and 32 DC developmental
      arrays), all these expression profiles were analyzed by the methods of
      hierarchical clustering, principal component analysis, nearest-neighborhood, and
      self-organizing maps. The results indicate that expression profiles of DC sarcoma
      are closer to those of the DC progenitors and hematopoietic stem cells from bone
      marrow compared with the sorted DCs from spleen. The results support the
      hypothesis that cancers (tumors or sarcomas) arise from stem cells. It is
      suggested that the DC sarcomas are more similar to the DC progenitors and
      hematopoietic stem cells than the relative mature DCs in gene expressions on the
      large-scale.

PMID- 15845379
TI  - In vivo measurement of DNA synthesis rates of colon epithelial cells in
      carcinogenesis.
AB  - We describe here a highly sensitive technique for measuring DNA synthesis rates
      of colon epithelial cells in vivo. Male SD rats were given (2)H(2)O (heavy
      water). Colon epithelial cells were isolated, DNA was extracted, hydrolyzed to
      deoxyribonucleosides, and the deuterium enrichment of the deoxyribose moiety was
      determined by gas chromatographic/mass spectrometry. Turnover time of colon
      crypts and the time for migration of cells from basal to top fraction of the
      crypts were measured. These data were consistent with cell cycle analysis and
      bromodeoxyuridine labeling. By giving different concentrations of a promoter,
      dose-dependent increases in DNA synthesis rates were detected, demonstrating the
      sensitivity of the method. Administration of a carcinogen increased DNA synthesis
      rates cell proliferation in all fractions of the crypt. In conclusion, DNA
      synthesis rates of colon epithelial cells can be measured directly in vivo using
      stable-isotope labeling. Potential applications in humans include use as a
      biomarker for cancer chemoprevention studies.

PMID- 15845380
TI  - Spore-displayed streptavidin: a live diagnostic tool in biotechnology.
AB  - Streptavidin, which is one of the most widely used proteins in biotechnological
      application field and is active only in tetrameric form, was surface expressed on
      the surface of Bacillus subtilis spore. Spore coat protein of B. subtilis, CotG,
      was used as an anchoring motif to display streptavidin. FACS using anti
      streptavidin antibody was used for the verification of surface localization of
      expressed CotG-streptavidin fusion protein. FACS and dot-blot were used for the
      verification of biological activity of displayed streptavidin with FITC-labeled
      biotin.

PMID- 15845381
TI  - Specific inactivation of cysteine protease-type cathepsin by singlet oxygen
      generated from naphthalene endoperoxides.
AB  - Singlet oxygen is a causal factor in light-induced skin photoaging and the
      cytotoxic process of tumor cells in photodynamic chemotherapy. To develop a
      better understanding of the functional consequences of protein modification by
      singlet oxygen, the effects of naphthalene endoperoxide on lysosomal protease,
      cathepsin, were examined. When the soluble fraction of normal human fetal skin
      fibroblast cells was treated with the endoperoxide, the activities of cysteine
      proteases, cathepsins B and L/S, were inhibited, but that of aspartate protease,
      cathepsin D/E, was not. The reduction of the endoperoxide-treated soluble
      fractions by treatment with dithiothreitol barely recovered the activities.
      Cathepsin B, purified from normal human liver, exhibited similar profiles to that
      in cytosol. These data suggest that singlet oxygen oxidatively modifies an amino
      acid residue essential for catalysis and consequently results in the irreversible
      inactivation of cysteine protease-type cathepsin.

PMID- 15845382
TI  - ERp57 binds competitively to protein disulfide isomerase and calreticulin.
AB  - In this study, we screened for protein disulfide isomerase (PDI)-binding proteins
      in bovine liver microsomes under strict salt concentrations, using affinity
      column chromatography. One main band observed using SDS-PAGE was identified as
      ERp57 (one of the PDI family proteins) by LC-MS/MS analysis. The K(D) value of
      PDI binding to ERp57 was calculated as 5.46x10(-6)M with the BIACORE system. The
      interactions between PDI and ERp57 occurred specifically at their a and b
      domains, respectively. Interestingly, low concentrations of ERp57 enhanced the
      chaperone activity of PDI, while high concentrations interfered with chaperone
      activity. On the other hand, ERp57 did not affect the isomerase activity of PDI.
      Additionally, following pre-incubation of ERp57 with calreticulin (CRT),
      decreased interactions were observed between ERp57 and PDI, and vice versa. Based
      on the data, we propose that once ERp57 binds to PDI or CRT, the resultant
      complex inhibits further interactions. Therefore, ERp57 selectively forms a
      protein-folding complex with PDI or CRT in ER.

PMID- 15845383
TI  - Differential Ca2+ sensitivity of RyR2 mutations reveals distinct mechanisms of
      channel dysfunction in sudden cardiac death.
AB  - Arrhythmogenic point mutations in RyR2 result in abnormal Ca(2+) release
      following cardiac stimulation, leading to sudden cardiac death (SCD). Recently,
      we have demonstrated that significant functional differences exist between SCD
      linked RyR2 mutations. Here, we investigated the molecular basis of this
      heterogeneity and determined the sensitivity of mutant RyR2 channels to
      cytoplasmic [Ca(2+)] ([Ca(2+)](c)) in living cells. Using streptolysin-O
      permeabilised human embryonic kidney cells, [Ca(2+)](c) was clamped in cells
      expressing GFP-tagged wild-type (WT) or SCD-linked RyR2 mutants (L(433)P,
      N(2386)I, and R(176)Q/T(2504)M). Although resting [Ca(2+)](c) was comparable in
      all cells, RyR2 mutants were characterised by a profound loss of Ca(2+)-dependent
      inhibition following caffeine stimulation when compared with WT channels. The ER
      Ca(2+) store was not perturbed in these experiments. Our findings support the
      hypothesis that SCD-linked mutational loci may be an important mechanistic
      determinant of RyR2 dysfunction and indicate that there is unlikely to be a
      unifying mechanism for channel dysfunction in SCD.

PMID- 15845384
TI  - Human and murine glycerol kinase: influence of exon 18 alternative splicing on
      function.
AB  - Glycerol kinase (GK) is a key enzyme in glycerol metabolism with two
      alternatively spliced forms-one with an 87bp insertion corresponding to exon 18
      (GK+EX18), and one lacking exon 18 (GK-EX18). We report the expression of GK+/
      EX18 in various tissues and cell lines, as well as their enzymatic
      characteristics and subcellular localization. RT-PCR revealed differential
      expression in tissues and cell lines. Northern blot analysis revealed that both
      forms of the murine ortholog, Gyk, were highly expressed in murine heart and
      increased during embryonic development. K(m) values for glycerol for GK+/-EX18
      were not significantly different, although GK-EX18 had a higher V(max) for
      glycerol. GK-EX18 had a lower K(m) and V(max) for ATP than GK+EX18.
      Immunofluorescence experiments showed that GK+EX18 co-localized to the
      mitochondria and the perinuclear region while GK-EX18 had a diffuse expression
      pattern. These data suggest specific and divergent roles for GK+EX18 and GK-EX18
      in cellular metabolism and development.

PMID- 15845385
TI  - Protein kinase CK2 interacts with Chk2 and phosphorylates Mre11 on serine 649.
AB  - The Mre11-Rad50-Nbs1 protein complex has been known to be involved in a variety
      of DNA metabolic events that involve DNA double-strand breaks (DSBs). The
      phosphorylation of Mre11 is increased in response to ionizing radiation, which
      suggests that phosphorylation of Mre11 may be an important regulatory mechanism
      of this complex. Mre11-phosphorylating kinase activities were observed in Chk2
      immunoprecipitates and HeLa nuclear extracts. Through the tandem affinity tagging
      system and conventional chromatography, this kinase was purified and identified
      as protein kinase CK2. CK2 phosphorylates Mre11 in vitro. In vitro kinase assay
      with a series of truncated Mre11 proteins as substrates for CK2 and site-directed
      mutagenesis showed that serine 649 of Mre11 is mainly phosphorylated by CK2 in
      vitro. In vivo labeling and phosphopeptide mapping analysis revealed that this
      phosphorylation occurs in vivo. These data implicate CK2 as a potential upstream
      regulator of Mre11 function.

PMID- 15845386
TI  - Discovery of a novel superfamily of type III polyketide synthases in Aspergillus
      oryzae.
AB  - Identification of genes encoding type III polyketide synthase (PKS) superfamily
      members in the industrially useful filamentous fungus, Aspergillus oryzae,
      revealed that their distribution is not specific to plants or bacteria. Among
      other Aspergilli (Aspergillus nidulans and Aspergillus fumigatus), A. oryzae was
      unique in possessing four chalcone synthase (CHS)-like genes (csyA, csyB, csyC,
      and csyD). Expression of csyA, csyB, and csyD genes was confirmed by RT-PCR.
      Comparative genome analyses revealed single putative type III PKS in Neurospora
      crassa and Fusarium graminearum, two each in Magnaporthe grisea and Podospora
      anserina, and three in Phenarocheate chrysosporium, with a phylogenic distinction
      from bacteria and plants. Conservation of catalytic residues in the CHSs across
      species implicated enzymatically active nature of these newly discovered
      homologs.

PMID- 15845387
TI  - Identification of a novel insulin-like growth factor binding protein gene
      homologue with tumor suppressor like properties.
AB  - Here we report the identification of a new insulin-like growth factor binding
      protein homologue, provisionally designated insulin-like growth factor binding
      related protein-4 (IGFBP-rP4). IGFBP-rP4 was found to be most closely related to
      IGFBP-7 with 52% amino acid homology and 43% amino acid identity, and shares a
      similar domain structure. Semi-quantitative RT-PCR expression analysis
      demonstrated a pattern of downregulation of this gene in multiple tumor samples
      including lung and colon cancer, compared to matched adjacent normal tissue.
      Western blotting revealed a protein of approximately 38kDa expressed in both the
      cell pellet and secreted into the supernatant of transiently transfected Cos-7
      cells. Cos-7 supernatants containing IGFBP-RP4 protein were observed to suppress
      the growth of HeLa cells in culture compared to vector controls. IGFBP-RP4
      directly transiently transfected into HeLa cells also further confirmed the
      growth suppressive properties of this protein. Together these data suggest that
      IGFBP-RP4 may be a novel putative tumor suppressor protein.

PMID- 15845388
TI  - tRNAPhe cleavage by aminoglycosides is triggered off by formation of an abasic
      site.
AB  - This communication reports the characteristics of the mechanism of highly
      specific tRNA(Phe) cleavage, which occurs in the anticodon loop in the presence
      of aminoglycoside antibiotic-neomycin B. The data prove that the cleavage
      requires previous depurination of the polynucleotide chain at position 37, which
      is occupied by a hypermodified guanine base-wybutine. The results suggest that
      the phenomenon, previously considered as selective with respect to the presence
      of tRNA hypermodification, may concern far more RNA molecules, namely the ones
      carrying abasic sites.

PMID- 15845389
TI  - The serine/threonine kinases SGK1, 3 and PKB stimulate the amino acid transporter
      ASCT2.
AB  - The human Na(+)-dependent neutral amino acid transporter type 2 (hASCT2/SLC1A5)
      plays an important role in the transport of neutral amino acids in epithelial
      cells. The serine and threonine kinases SGK1-3 and protein kinase B have been
      implicated in the regulation of several members of the SLC1 transporter family by
      enhancing their plasma membrane abundance. The present study explored whether
      those kinases modulate hASCT2. In Xenopus oocytes heterologously expressing
      hASCT2, coexpression of constitutively active (S422D)SGK1, (S419D)SGK3 or
      (T308DS473D)PKB upregulated the transporter activity. The stimulation requires
      the catalytical activity of the kinases since the inactive mutants (K127N)SGK1,
      (K191N)SGK3, and (T308AS473A)PKB failed to modulate the transporter. According to
      kinetic analysis and chemiluminescence assays, SGK1 and SGK3 modulate hASCT2 by
      enhancing the transporter abundance in the plasma membrane. As SGK1, 3 and PKB
      are activated by insulin and IGF1, the described mechanisms presumably
      participate in the hormonal stimulation of cellular amino acid uptake.

PMID- 15845390
TI  - Impairment of redox state and dopamine level induced by alpha-synuclein
      aggregation and the prevention effect of hsp70.
AB  - One hypothesis for the etiology of Parkinson's disease (PD) is that the formation
      of proteinaceous inclusion, which is mainly composed of alpha-synuclein, may
      contribute to the selective loss of dopaminergic neurons. To further explore the
      role of alpha-synuclein in neurodegeneration of PD, we examined the possible
      effects of aggregated alpha-synuclein on the intracellular redox state, dopamine
      level, and cell death of SK-N-SH cells. Our present studies show that alpha
      synuclein aggregation gives rise to both elevated intracellular oxidative state
      and dopamine level in SK-N-SH cells. Moreover, alpha-synuclein aggregation
      results in a higher ratio of apoptosis population (55.8%+/-SEM) in cells
      overexpressing alpha-synuclein aggregation, compared to their normal control
      groups (8.0%+/-SEM). In contrast, coexpression of hsp70 with alpha-synuclein
      suppresses the oxidative state shift, restores the normal dopamine levels and
      blocks neuron cell loss. Therefore, our data provided one possible mechanism by
      which the alpha-synuclein aggregation may lead to the neurodegeneration in PD via
      regulating the level of cytoplasmic dopamine and then disturbing the
      intracellular redox homeostasis. On the other hand, hsp70 can mitigate the
      degenerative effect conferred by alpha-synuclein, acting as a protective factor
      in treatment of PD.

PMID- 15845391
TI  - Triggering of TLR3 by polyI:C in human corneal epithelial cells to induce
      inflammatory cytokines.
AB  - Epithelial cells of the ocular surface are key in the first-line defense as a
      part of the mucosal immune system against pathogens. We investigated whether
      polyI:C induces the production by human corneal epithelial cells (HCEC) of pro
      inflammatory cytokines and IFN-beta, and whether Toll-like receptor (TLR)-3
      expression is amplified by polyI:C. TLR3 was expressed on the surface of HCEC.
      Stimulation with polyI:C elicited the elevated production and mRNA expression of
      IL-6 and IL-8 in HCEC. While polyI:C induced IFN-beta, far stronger than human
      fibroblasts, and TLR3 gene expression in HCEC, LPS stimulation did not.
      Similarly, polyI:C, but not LPS, induced the gene expression of IkappaBalpha and
      MAIL, members of the IkappaB family, in HCEC. The innate immune response of HCEC
      is distinct from that of immune-competent cells, and we suggest that this is
      indicative of the symbiotic relationship between corneal epithelium and microbes
      inhabiting the ocular surface.

PMID- 15845392
TI  - The rapamycin analog CCI-779 is a potent inhibitor of pancreatic cancer cell
      proliferation.
AB  - We present immunohistochemical evidence that the mTOR/p70s6k pathway is activated
      in pancreatic tumors and show that the mTOR inhibitor and rapamycin analog CCI
      779 potently suppresses the proliferation of pancreatic cancer cells. Consistent
      with a recent study, CCI-779 increased c-Jun phosphorylation (Ser63) in a dose-
      and time-dependent manner, and induced apoptosis in p53-defective BxPC-3 cells.
      In contrast to the study, however, we observed that CCI-779 concomitantly
      increased c-Jun protein levels and that its ability to induce apoptosis might not
      require the activated c-Jun. Furthermore, CCI-779 neither induced c-Jun
      phosphorylation in other p53-defective pancreatic cancer cells (MiaPaCa-2) nor
      inhibited their proliferation. c-Jun, in fact, appeared to be partly responsible
      for the resistance of MiaPaCa-2 cells to CCI-779. Together, these results
      indicate a complex role for c-Jun in cellular responses to CCI-779 and provide an
      important basis for investigating CCI-779 further as a potential therapeutic
      agent for pancreatic tumors.

PMID- 15845393
TI  - Wortmannin induces zebrafish cardia bifida through a mechanism independent of
      phosphoinositide 3-kinase and myosin light chain kinase.
AB  - Cardia bifida is an anomaly of the embryonic heart in which the bilateral
      myocardial rudiments fail to travel to the midline, resulting in the formation of
      two separate hearts in lateral positions. In zebrafish, eight loci responsible
      for the cardia bifida phenotype were identified in the large-scale genetic
      screen. Wortmannin has been reported to be a highly selective inhibitor of
      phosphoinositide 3-kinase and myosin light chain kinase activity. We provide the
      first evidence that wortmannin treatment of zebrafish embryos can induce cardia
      bifida in a dose-dependent manner and that wortmannin alters cardiac development
      between 6 and 16 h post-fertilization. In addition, we demonstrate that
      wortmannin induces zebrafish cardia bifida through a mechanism independent of
      phosphoinositide 3-kinase and myosin light chain kinase. Our findings may provide
      new insights into the cardiomyocyte function and disfunction.

PMID- 15845394
TI  - Phosphorylated IkappaBalpha is a component of Lewy body of Parkinson's disease.
AB  - Ubiquitin is one of the major components of Lewy bodies (LB), the pathological
      hallmark of Parkinson's disease (PD). Here, we identified that a phosphorylated
      form of IkappaBalpha (pIkappaBalpha), an inhibitor of NF-kappaB, and SCF(beta
      TrCP), the ubiquitin ligase of pIkappaBalpha, are components of LB in brains of
      PD patients. In vitro studies identified those proteins in the ubiquitin- and
      alpha-synuclein (known as the major component of LB)-positive LB-like inclusions
      generated in dopaminergic SH-SY5Y cells treated with MG132, a proteasome
      inhibitor. Intriguingly, IkappaBalpha migration into such ubiquitinated
      inclusions in cells treated with MG132 was inhibited by a cell-permeable peptide
      known to block phosphorylation of IkappaBalpha, although this peptide did not
      influence cell viability under proteasomal inhibition. Our results indicate that
      phosphorylation of IkappaBalpha plays a role in the formation of IkappaBalpha
      containing inclusions caused by proteasomal dysfunction, and that the generation
      of such inclusion is independent of cell death caused by impairment of
      proteasome.

PMID- 15845395
TI  - Living microtransporter by uni-directional gliding of Mycoplasma along
      microtracks.
AB  - The gliding bacterium Mycoplasma mobile adheres to plastic surfaces and moves
      around vigorously. However, it has not been possible to control the direction of
      movements on plain surfaces. Here we report that, on patterned lithographic
      substrates, M. mobile cells are unable to climb tall walls and move along the
      bottom edge of the walls. This property to move persistently along walls enabled
      us to design patterns that control direction of movements, resulting in uni
      directional circling or one-way gating between two areas. Furthermore, cells
      loaded with streptavidin beads following biotinylation of surface proteins moved
      at normal speeds. These bacteria could be useful as living microtransporters,
      carrying cargo around within micrometer-scale spaces.

PMID- 15845396
TI  - Apolipoprotein E activates the low-activity form of human phospholipid transfer
      protein.
AB  - Phospholipid transfer protein (PLTP) exists in a high-activity (HA-PLTP) and a
      low-activity form (LA-PLTP) in the circulation. LA-PLTP is associated with apoA-I
      while the HA-PLTP complex is enriched with apoE. To study the interaction of PLTP
      with apolipoproteins, we carried out surface plasmon resonance analyses. These
      demonstrated a concentration-dependent binding of recombinant human PLTP, which
      represents an active PLTP form, and LA-PLTP to apoE, apoA-I, and apoA-IV within a
      nanomolar K(D) range. To study whether LA-PLTP can be transformed into an active
      form, we incubated it in the presence of proteoliposomes containing apoE, apoA-I
      or apoA-IV. The apoE proteoliposomes induced a concentration-dependent activation
      of LA-PLTP. ApoA-IV proteoliposomes also activated LA-PLTP in a concentration
      dependent manner, whereas apoA-I proteoliposomes had no such effect. These
      observations suggest that PLTP is capable of interacting with apoE, apoA-I, and
      apoA-IV, and that these interactions regulate PLTP-activity levels in plasma.

PMID- 15845397
TI  - Bifunctional isocitrate-homoisocitrate dehydrogenase: a missing link in the
      evolution of beta-decarboxylating dehydrogenase.
AB  - Beta-decarboxylating dehydrogenases comprise 3-isopropylmalate dehydrogenase,
      isocitrate dehydrogenase, and homoisocitrate dehydrogenase. They share a high
      degree of amino acid sequence identity and occupy equivalent positions in the
      amino acid biosynthetic pathways for leucine, glutamate, and lysine,
      respectively. Therefore, not only the enzymes but also the whole pathways should
      have evolved from a common ancestral pathway. In Pyrococcus horikoshii, only one
      pathway of the three has been identified in the genomic sequence, and PH1722 is
      the sole beta-decarboxylating dehydrogenase gene. The organism does not require
      leucine, glutamate, or lysine for growth; the single pathway might play multiple
      (i.e., ancestral) roles in amino acid biosynthesis. The PH1722 gene was cloned
      and expressed in Escherichia coli and the substrate specificity of the
      recombinant enzyme was investigated. It exhibited activities on isocitrate and
      homoisocitrate at near equal efficiency, but not on 3-isopropylmalate. PH1722 is
      thus a novel, bifunctional beta-decarboxylating dehydrogenase, which likely plays
      a dual role in glutamate and lysine biosynthesis in vivo.

PMID- 15845398
TI  - Association of soluble epoxide hydrolase gene polymorphism with insulin
      resistance in type 2 diabetic patients.
AB  - The insulin resistance found in diabetes is influenced by vascular tone and local
      blood flow. Endothelial-derived hyperpolarizing factor (EDHF) functions as a
      potent vasodilator to regulate vascular tone, and its production is regulated by
      soluble epoxide hydrolase (sEH). In this study, we examined the genotype
      distribution and allele frequency of sEH gene G860A (Arg287Gln) polymorphism in
      Japanese subjects (n=499) (non-diabetic subjects, n=205; type 2 diabetic
      patients, n=294). Also, to accurately evaluate insulin resistance, we performed
      the euglycemic hyperinsulinemic clamp test for each type 2 diabetic patient
      (n=86) from whom agreement was obtained, and then examined a possible association
      of sEH gene G860A polymorphism with insulin resistance status. There was no
      significant difference in genotype distribution and allele frequency between non
      diabetic subjects and type 2 diabetic patients. Interestingly, however, there was
      close association of sEH gene G860A (Arg287Gln) polymorphism with insulin
      resistance in type 2 diabetic patients, which was not observed in non-diabetic
      subjects. These results suggest that sEH and EDHF play some important role in the
      pathogenesis of insulin resistance found in type 2 diabetes.

PMID- 15845399
TI  - A general fluorescence-based coupled assay for S-adenosylmethionine-dependent
      methyltransferases.
AB  - We have developed a simple and sensitive fluorescence-based two-step coupled
      enzyme assay to report the activity of S-adenosylmethionine-dependent
      methyltransferases. This assay relies on a fluorescein-cystamine-methyl red (FL-S
      S-MR) reporter molecule that can be activated by thiols. In the absence of
      thiols, fluorescence from the reporter is quenched through fluorescence resonance
      energy transfer between the two chromophores. In this report, we use catechol-O
      methyltransferase with the addition of S-adenosylhomocysteine hydrolase to
      produce the thiol homocysteine. The presence of homocysteine leads to disulfide
      bond cleavage in the cystamine tether and fluorescence dequenching as the
      uncoupled chromophores are diluted into the surrounding media. The sensitivity
      and specificity of FL-S-S-MR to thiols enabled detection of <or=1 microM
      concentrations of homocysteine, suggesting that this assay is sensitive enough to
      detect biologically relevant amounts of homocysteine. We believe that this
      fluorescence reporter approach may be generalizable to all enzymatic or chemical
      assays that produce thiols.

PMID- 15845400
TI  - In vitro transcription termination activity of the Drosophila mitochondrial DNA
      binding protein DmTTF.
AB  - DmTTF is a Drosophila melanogaster mitochondrial DNA-binding protein which binds
      specifically to two homologous non-coding sequences located at the 3' ends of
      blocks of genes encoded on opposite strands. In order to test whether this
      protein acts as transcription termination factor, we assayed the capacity of
      DmTTF to arrest in vitro the transcription catalyzed by mitochondrial and
      bacteriophage RNA polymerases. Experiments with human S-100 extracts showed that
      DmTTF is able to arrest the transcription catalyzed by human mitochondrial RNA
      polymerase bidirectionally, independently of the orientation of the protein-DNA
      complex. On the contrary when T3 or T7 RNA polymerases were used, we found that
      DmTTF prevalently arrests transcription when the DNA-binding site was placed in
      the reverse orientation with respect to the incoming enzymes. These results
      demonstrate that DmTTF is a transcription termination factor with a biased
      polarity and suggest that the DNA-bound protein is structurally asymmetrical,
      exposing two different faces to RNA polymerases travelling on opposite
      directions.

PMID- 15845401
TI  - Molecular cloning and characterization of a novel Gq-coupled orphan receptor
      GPRg1 exclusively expressed in the central nervous system.
AB  - G-protein-coupled receptors (GPCRs) are important mediators of signal
      transduction and are therefore potential targets for pharmacological
      therapeutics. Here, we report the identification and characterization of an
      orphan GPCR, termed GPRg1, which was found in the GenBank database following
      searches with GPCR query sequences. Quantitative PCR analysis revealed that GPRg1
      transcripts are expressed almost exclusively in the brain. Moreover, in situ
      hybridization experiments in brain demonstrated that GPRg1 is abundantly
      expressed in the ventrolateral region of caudate putamen, the habenular nucleus,
      the zona incerta, and the medial mammillary nucleus. In addition, overexpression
      of GPRg1 in 293-EBNA cells activates serum response factor mediated
      transcription, which was completely inhibited by the Gq/11 selective inhibitor YM
      254890, indicating the coupling of GPRg1 with Gq/11. These findings suggest that
      GPRg1 is a candidate receptor for novel physiologically bioactive substrates and
      that it plays important roles in the central nervous system.

PMID- 15845402
TI  - Rotary torque produced by proton motive force in FoF1 motor.
AB  - We have attempted direct observation of the light-driven rotation of a FoF(1)-ATP
      motor. The FoF(1)-ATP motor was co-reconstituted by the deletion-delta subunit of
      FoF(1)-ATP synthase with bacteriorhodopsins (BRs) into a liposome. The BR
      converts radiation energy into electrochemical gradient of proton to drive the
      FoF(1)-ATP motor. Therefore, the light-driven rotation of FoF(1)-ATP motor has
      been directly observed by a fluorescence microscopy using a fluorescent actin
      filament connected to beta-subunit as a marker of its orientation. The rotational
      torque value of the Fo motor was calculated as 27.93+/-1.88pNnm. The ATP motor is
      expected to be a promising rotary molecular motor in the development of
      nanodevices.

PMID- 15845403
TI  - Purification and characterization of an alpha-glucosidase from germinating millet
      seeds.
AB  - An alpha-glucosidase (alpha-D-glucoside glucohydrolase, EC 3.2.1.20) was isolated
      from germinating millet (Panicum miliaceum L.) seeds by a procedure that included
      ammonium sulfate fractionation, chromatography on CM-cellulofine/Fractogel EMD
      SO(3), Sephacryl S-200 HR and TSK gel Phenyl-5 PW, and preparative isoelectric
      focusing. The enzyme was homogenous by SDS-PAGE. The molecular weight of the
      enzyme was estimated to be 86,000 based on its mobility in SDS-PAGE and 80,000
      based on gel filtration with TSKgel super SW 3000, which showed that it was
      composed of a single unit. The isoelectric point of the enzyme was 8.3. The
      enzyme readily hydrolyzed maltose, malto-oligosaccharides, and alpha-1,4-glucan,
      but hydrolyzed polysaccharides more rapidly than maltose. The K(m) value
      decreased with an increase in the molecular weight of the substrate. The value
      for maltoheptaose was about 4-fold lower than that for maltose. The enzyme
      preferably hydrolyzed amylopectin in starch, but also readily hydrolyzed
      nigerose, which has an alpha-1,3-glucosidic linkage and exists as an abnormal
      linkage in the structure of starch. In particular, the enzyme readily hydrolyzed
      millet starch from germinating seeds that had been degraded to some extent.

PMID- 15845404
TI  - Characterisation of recombinant epithiospecifier protein and its over-expression
      in Arabidopsis thaliana.
AB  - Epithiospecifier protein (ESP) is a protein that catalyses formation of
      epithionitriles during glucosinolate hydrolysis. In vitro assays with a
      recombinant ESP showed that the formation of epithionitriles from
      alkenylglucosinolates is ESP and ferrous ion dependent. Nitrile formation in
      vitro however does not require ESP but only the presence of Fe(II) and
      myrosinase. Ectopic expression of ESP in Arabidopsis thaliana Col-5 under control
      of the strong viral CaMV 35S promoter altered the glucosinolate product profile
      from isothiocyanates towards the corresponding nitriles.

PMID- 15845405
TI  - Overexpression of squalene synthase in Eleutherococcus senticosus increases
      phytosterol and triterpene accumulation.
AB  - Squalene synthase (SS) catalyzes the first committed step in sterol and
      triterpenoid biosynthesis. Transgenic Eleutherococcus senticosus Rupr. and Maxim.
      plants were generated by introducing an SS-encoding gene derived from Panax
      ginseng (PgSS1) together with genes expressing hygromycin phosphotransferase and
      green fluorescent protein (GFP) through Agrobacterium-mediated transformation.
      Early globular embryo clusters developing from the embryogenic callus were used
      for Agrobacterium-mediated transformation. Transformants were selected on
      Murashige Skoog medium containing 25 mg/L hygromycin. Hygromycin-resistant
      somatic embryos developed into plants after the cotyledonary embryos were treated
      with 14.4 microM gibberellic acid. Transformation was confirmed by polymerase
      chain reaction, Southern, and GFP analyses. The SS enzyme activity of the
      transgenic plants was up to 3-fold higher than that of wild-type plants. In
      addition, GC-MS and HPLC analysis revealed that phytosterols (beta-sitosterol and
      stigmasterol) as well as triterpene saponins (ciwujianosides B (1), C(1) (2),
      C(2) (3), C(3) (4), C(4) (5), D(1) (6) and D(2) (7)) levels in transgenic E.
      senticosus were increased by 2- to 2.5-fold. These results suggest that the
      metabolic engineering of E. senticosus to enhance production of phytosterols and
      triterpenoids by introducing the PgSS1 gene was successfully achieved by
      Agrobacterium-mediated genetic transformation.

PMID- 15845406
TI  - Cloning and immunolocalization of an antifungal chitinase in jelly fig (Ficus
      awkeotsang) achenes.
AB  - A 30-kDa protein extracted from the pericarpial portion of jelly fig (Ficus
      awkeotsang Makino) achenes has been identified as a thermostable chitinase based
      on its enzymatic activity. A cDNA fragment encoding the precursor protein
      (including a cleavable signal sequence) of this chitinase was obtained by PCR
      cloning, and subsequently confirmed by immunological recognition of its
      overexpressed protein in Escherichia coli. Homology modeling predicted that this
      thermostable chitinase in jelly fig achenes comprised a stable (betaalpha)(8)
      barrel fold with three pairs of disulfide linkage. Immunostaining indicated that
      this chitinase was exclusively localized in the pericarpial region but not in the
      seed cells where bulky protein bodies and massive oil bodies were accumulated.
      Spore germination of Colletotrichum gloeosporioides, a common post-harvest
      pathogen infecting ripening fruit of jelly fig and many other fruits, was
      inhibited by this chitinase purified from achenes. It is suggested that the
      biological function of the thermostable chitinase in the pericarp of jelly fig
      achenes is to protect the nutritive seeds from fungal attack during fruit
      ripening.

PMID- 15845407
TI  - Biosynthesis of benzofuran derivatives in root cultures of Tagetes patula via
      phenylalanine and 1-deoxy-D-xylulose 5-phosphate.
AB  - Root cultures of Tagetes patula L. cv. Carmen were grown with a mixture of
      unlabeled glucose and [U-(13)C(6)]glucose or [1-(13)C(1)]glucose as carbon
      source. Isoeuparin and (-)-4-hydroxytremetone were isolated by solvent extraction
      of the cultured tissue, purified by chromatography and analysed by (1)H and (13)C
      NMR spectroscopy. Amino acids obtained by hydrolysis of protein from the same
      experiments were used for the reconstruction of the labelling patterns in central
      metabolic intermediates. These labelling patterns were used for the prediction of
      isotopolog compositions in the benzofuranone derivatives via different
      hypothetical pathways. Comparison with the experimentally observed isotopolog
      distributions showed that the benzenoid ring and the acetoxy group are
      exclusively or predominantly (>98%) derived from phenylalanine and not from
      acetyl-CoA via a polyketide-type biosynthesis. The isopropylidene side chain and
      two carbon atoms of the furan and dihydrofuran moiety, respectively, originate
      from an isoprenoid building block obtained exclusively or predominantly (>98%)
      via the deoxyxylulose phosphate pathway. The exomethylene atom of the
      isopropylidene side chain is biosynthetically equivalent to the (Z)-methyl group
      of dimethylallyl diphosphate. The data indicate that isoeuparin and (-)-4
      hydroxytremetone are assembled from 4-hydroxyacetophenone and dimethylallyl
      diphosphate via prenyl-substituted 4-hydroxyacetophenone and dihydrobenzofurans
      as intermediates.

PMID- 15845408
TI  - Stemodane skeletal rearrangement: chemistry and microbial transformation.
AB  - Solvolytic rearrangement of the C/D ring system of the tetracyclic diterpenoid
      stemodinone (2) afforded the compounds 15(13-->12)abeo-13beta-hydroxystemaran-2
      one (5) and 15(8-->9)abeo-8beta(H)-12beta-hydroxystachan-2-one (10). Terpene 5
      possesses a novel diterpene skeleton. Oxidation of these compounds yielded their
      respective diketones. Bioconversion of 5 by Rhizopus oryzae yielded 15(13-
      >12)abeo-7beta,13beta-dihydroxystemaran-2-one (18) while microbial transformation
      of 10 provided 15(8-->9)abeo-8beta(H)-6alpha,12beta-dihydroxystachan-2-one (19),
      15(8-->9)abeo-8beta(H)-7beta,12beta-dihydroxystachan-2-one (20) and 15(8-->9)abeo
      8beta(H)-6alpha,12beta,14beta-trihydroxystachan-2-one (21). A rationale for the
      formation of the rearranged compounds is proposed.

PMID- 15845409
TI  - Hydrogen, carbon and nitrogen isotopic fractionations during chlorophyll
      biosynthesis in C3 higher plants.
AB  - We determined hydrogen, carbon and nitrogen isotopic compositions of chlorophylls
      a and b isolated from leaves of five C3 higher plant species (Benthamidia
      japonica, Prunus japonica, Acer carpinifolium, Acer argutum and Querus
      mongloica), and hydrogen and carbon isotopic compositions of phytol and
      chlorophyllides in the chlorophylls to understand isotopic fractionations
      associated with chlorophyll biosynthesis in these species. Chlorophylls are
      depleted in D relative to ambient water by approximately 189 per thousand and
      enriched in (13)C relative to bulk tissue by approximately 1.6 per thousand.
      These data can be explained by the contribution of isotopic fractionations during
      phytol and chlorophyllide biosyntheses. Phytol is more depleted in both D (by
      approximately 308 per thousand) and (13)C (by approximately 4.3 per thousand),
      while chlorophyllides are less depleted in D (by approximately 44 per thousand)
      and enriched in (13)C (by approximately 4.8 per thousand). Such inhomogeneous
      distribution of isotopes in chlorophylls suggests that (1) the phytol in
      chlorophylls reflects strong D- and (13)C-depletions due to the isotopic
      fractionations during the methylerythritol phosphate pathway followed by
      hydrogenation, and (2) the chlorophyllides reflect D- and (13)C-enrichments in
      tricarboxylic acid cycle. On the other hand, chlorophylls are slightly (
      approximately 1.2 per thousand) depleted in (15)N relative to the bulk tissue,
      indicating that net isotopic fractionation of nitrogen during chlorophyll
      biosynthesis is small compared with those of hydrogen and carbon.

PMID- 15845410
TI  - Comparative phytochemical analysis of four Mexican Nymphaea species.
AB  - Four Mexican Nymphaea species, N. ampla, N. pulchella, N. gracilis and N. elegans
      belonging to subgenera Brachyceras were analyzed. In this work two 5-glycosyl
      isoflavones, 7,3',4'-trihydroxy-5-O-beta-D-(2''-acetyl)-xylopyranosylisoflavone
      (1) and 7,3',4'-trihydroxy-5-O-alpha-L-rhamnopyranosylisoflavone (2), were
      isolated from N. ampla and N. pulchella, respectively, together with other known
      3-glycosyl flavones and triterpene saponins from the same four species. The
      structures were elucidated by 1D and 2D NMR, FABMS, and other spectroscopic
      analyses. These results confirmed that the four species were different from each
      other and established that N. pulchella represents a different taxa than N.
      ampla. In addition, the 5-glycosyl isoflavones could be considered as a taxonomic
      character of this group of plants.

PMID- 15845411
TI  - Glucans of lichenized fungi: significance for taxonomy of the genera Parmotrema
      and Rimelia.
AB  - The glucans of lichenized fungi are an important class of polysaccharides with
      structural and chemotaxonomic roles. The water-insoluble glucans of the genus
      Parmotrema (P. austrosinense, P. delicatulum, P. mantiqueirense, P. schindleri,
      and P. tinctorum) and those of Rimelia (R. cetrata and R. reticulata), were
      investigated in order to evaluate the significance in chemotyping, with nigeran
      [(1-->3),(1-->4)-alpha-glucan] and lichenan [(1-->3),(1-->4)-beta-glucan]
      characterized using (1)H and (13)C NMR, methylation analysis, and controlled
      Smith degradations. Results from all species were similar, suggesting that glucan
      chemistry does not support separation of Rimelia from Parmotrema.

PMID- 15845412
TI  - Composition of the essential oil of the liverwort Radula perrottetii of Japanese
      origin.
AB  - Analysis of the essential oil of the liverwort Radula perrottetii afforded two
      novel viscidane diterpenes, viscida-3,9,14-triene (1), viscida-3,11(18),14-triene
      (2), four bisabolane sesquiterpenes, bisabola-2,6,11-triene (3), bisabola
      1,3,5,7(14),11-pentaene (4), bisabola-1,3,5,7,11-pentaene (5), 6,7-epoxybisabola
      2,11-diene (6), and 1-methoxy-4-(2-methylpropenyl)benzene (7) as new natural
      products. In addition, the known compounds bisabola-1,3,5,7(14),10-pentaene (8),
      ar-tenuifolene (9), alpha-helmiscapene (10), and beta-helmiscapene (11) were also
      isolated. Isolation was carried out by preparative gas chromatography, and the
      structures were established by extensive NMR analysis. This is the first finding
      of viscidane diterpenes in liverworts. Compounds 8, 9 and the rarely encountered
      eudesmane sesquiterpene hydrocarbons 10 and 11 are reported for the first time
      from R. perrottetii.

PMID- 15845414
TI  - Organic anion transporter (Slc22a) family members as mediators of toxicity.
AB  - Exposure of the body to toxic organic anions is unavoidable and occurs from both
      intentional and unintentional sources. Many hormones, neurotransmitters, and
      waste products of cellular metabolism, or their metabolites, are organic anions.
      The same is true for a wide variety of medications, herbicides, pesticides, plant
      and animal toxins, and industrial chemicals and solvents. Rapid and efficient
      elimination of these substances is often the body's best defense for limiting
      both systemic exposure and the duration of their pharmacological or toxicological
      effects. For organic anions, active transepithelial transport across the renal
      proximal tubule followed by elimination via the urine is a major pathway in this
      detoxification process. Accordingly, a large number of organic anion transport
      proteins belonging to several different gene families have been identified and
      found to be expressed in the proximal nephron. The function of these
      transporters, in combination with the high volume of renal blood flow,
      predisposes the kidney to increased toxic susceptibility. Understanding how the
      kidney mediates the transport of organic anions is integral to achieving desired
      therapeutic outcomes in response to drug interactions and chemical exposures, to
      understanding the progression of some disease states, and to predicting the
      influence of genetic variation upon these processes. This review will focus on
      the organic anion transporter (OAT) family and discuss the known members, their
      mechanisms of action, subcellular localization, and current evidence implicating
      their function as a determinant of the toxicity of certain endogenous and
      xenobiotic agents.

PMID- 15845415
TI  - Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP
      (ABCG2) in tissue defense.
AB  - In tumor cell lines, multidrug resistance is often associated with an ATP
      dependent decrease in cellular drug accumulation which is attributed to the
      overexpression of certain ATP-binding cassette (ABC) transporter proteins. ABC
      proteins that confer drug resistance include (but are not limited to) P
      glycoprotein (gene symbol ABCB1), the multidrug resistance protein 1 (MRP1, gene
      symbol ABCC1), MRP2 (gene symbol ABCC2), and the breast cancer resistance protein
      (BCRP, gene symbol ABCG2). In addition to their role in drug resistance, there is
      substantial evidence that these efflux pumps have overlapping functions in tissue
      defense. Collectively, these proteins are capable of transporting a vast and
      chemically diverse array of toxicants including bulky lipophilic cationic,
      anionic, and neutrally charged drugs and toxins as well as conjugated organic
      anions that encompass dietary and environmental carcinogens, pesticides, metals,
      metalloids, and lipid peroxidation products. P-glycoprotein, MRP1, MRP2, and
      BCRP/ABCG2 are expressed in tissues important for absorption (e.g., lung and gut)
      and metabolism and elimination (liver and kidney). In addition, these
      transporters have an important role in maintaining the barrier function of
      sanctuary site tissues (e.g., blood-brain barrier, blood-cerebral spinal fluid
      barrier, blood-testis barrier and the maternal-fetal barrier or placenta). Thus,
      these ABC transporters are increasingly recognized for their ability to modulate
      the absorption, distribution, metabolism, excretion, and toxicity of xenobiotics.
      In this review, the role of these four ABC transporter proteins in protecting
      tissues from a variety of toxicants is discussed. Species variations in substrate
      specificity and tissue distribution of these transporters are also addressed
      since these properties have implications for in vivo models of toxicity used for
      drug discovery and development.

PMID- 15845416
TI  - Molecular mechanisms of reduced glutathione transport: role of the MRP/CFTR/ABCC
      and OATP/SLC21A families of membrane proteins.
AB  - The initial step in reduced glutathione (GSH) turnover in all mammalian cells is
      its transport across the plasma membrane into the extracellular space; however,
      the mechanisms of GSH transport are not clearly defined. GSH export is required
      for the delivery of its constituent amino acids to other tissues, detoxification
      of drugs, metals, and other reactive compounds of both endogenous and exogenous
      origin, protection against oxidant stress, and secretion of hepatic bile. Recent
      studies indicate that some members of the multidrug resistance-associated protein
      (MRP/CFTR or ABCC) family of ATP-binding cassette (ABC) proteins, as well as some
      members of the organic anion transporting polypeptide (OATP or SLC21A) family of
      transporters contribute to this process. In particular, five of the 12 members of
      the MRP/CFTR family appear to mediate GSH export from cells namely, MRP1, MRP2,
      MRP4, MRP5, and CFTR. Additionally, two members of the OATP family, rat Oatp1 and
      Oatp2, have been identified as GSH transporters. For the Oatp1 transporter,
      efflux of GSH may provide the driving force for the uptake of extracellular
      substrates. In humans, OATP-B and OATP8 do not appear to transport GSH; however,
      other members of this family have yet to be characterized in regards to GSH
      transport. In yeast, the ABC proteins Ycf1p and Bpt1p transport GSH from the
      cytosol into the vacuole, whereas Hgt1p mediates GSH uptake across the plasma
      membrane. Because transport is a key step in GSH homeostasis and is intimately
      linked to its biological functions, GSH export proteins are likely to modulate
      essential cellular functions.

PMID- 15845417
TI  - Expression systems for cloned xenobiotic transporters.
AB  - One challenge of modern biology is to be able to match genes and their encoded
      proteins with events at the molecular, cellular, tissue, and organism levels, and
      thus, provide a multi-level understanding of gene function and dysfunction. How
      well this can be done for xenobiotic transporters depends on a knowledge of the
      genes expressed in the tissue, the cellular locations of the gene products (do
      they function for uptake or efflux?), and our ability to match substrates with
      transporters using information obtained from cloned transporters functioning in
      heterologous expression systems. Clearly, making a rational choice of expression
      system to use for the characterization and study of cloned xenobiotic
      transporters is a critical part of study design. This choice requires well
      defined goals, as well as an understanding of the strengths and weaknesses of
      candidate expression systems.

PMID- 15845418
TI  - Hepatic mitochondrial glutathione: transport and role in disease and toxicity.
AB  - Synthesized in the cytosol of cells, a fraction of cytosolic glutathione (GSH) is
      then transported into the mitochondrial matrix where it reaches a high
      concentration and plays a critical role in defending mitochondria against
      oxidants and electrophiles. Evidence mainly from kidney and liver mitochondria
      indicated that the dicarboxylate and the 2-oxoglutarate carriers contribute to
      the transport of GSH across the mitochondrial inner membrane. However,
      differential features between kidney and liver mitochondrial GSH (mGSH) transport
      seem to suggest the existence of additional carriers the identity of which
      remains to be established. One of the characteristic features of the hepatic
      mitochondrial transport of GSH is its regulation by membrane fluidity. Conditions
      leading to increased cholesterol deposition in the mitochondrial inner membrane
      such as in alcohol-induced liver injury decrease membrane fluidity and impair the
      mitochondrial transport of GSH. Depletion of mitochondrial GSH by alcohol is
      believed to contribute to the sensitization of the liver to alcohol-induced
      injury through tumor necrosis factor (TNF)-mediated hepatocellular death. Through
      control of mitochondrial electron transport chain-generated oxidants,
      mitochondrial GSH modulates cell death and hence its regulation may be a key
      target to influence disease progression and drug-induced cell death.

PMID- 15845420
TI  - Role of organic cation transporters in the renal handling of therapeutic agents
      and xenobiotics.
AB  - Organic cations (OCs) constitute a diverse array of compounds of physiological,
      pharmacological, and toxicological importance. Renal secretion of these
      compounds, which occurs principally along the proximal portion of the nephron,
      plays a critical role in regulating the concentration of OCs in the plasma and in
      clearing the body of potentially toxic xenobiotic OCs. Transepithelial OC
      transport in the kidney involves separate entry and exit steps at the basolateral
      and luminal aspects of renal tubular cells. It is increasingly apparent that
      basolateral and luminal OC transport reflects the concerted activity of a suite
      of separate transport processes arranged in parallel in each pole of proximal
      tubule cells. Most of the transporters that appear to dominate renal secretion of
      OCs belong to a single family of transport proteins: the OCT Family. The
      characterization of their activity, and their localization within distinct
      regions of the kidney, has permitted development of models describing the
      molecular and cellular basis of the renal secretion of OCs.

PMID- 15845421
TI  - Intestinal glutathione: determinant of mucosal peroxide transport, metabolism,
      and oxidative susceptibility.
AB  - The intestine is a primary site of nutrient absorption and a critical defense
      barrier against dietary-derived mutagens, carcinogens, and oxidants. Accumulation
      of oxidants like peroxidized lipids in the gut lumen can contribute to impairment
      of mucosal metabolic pathways, enterocyte dysfunction independent of cell injury,
      and development of gut pathologies, such as inflammation and cancer. Despite this
      recognition, we know little of the pathways of intestinal transport, metabolism,
      and luminal disposition of dietary peroxides in vivo or of the underlying
      mechanisms of lipid peroxide-induced genesis of intestinal disease processes.
      This chapter summarizes our current understanding of the determinants of
      intestinal absorption and metabolism of peroxidized lipids. I will review
      experimental evidence from our laboratory and others (Table 1) supporting the
      pivotal role that glutathione (GSH) and reduced nicotinamide adenine dinucleotide
      phosphate (NADPH) play in mucosal transport and metabolism of lipid
      hydroperoxides and how reductant availability can be compromised under chronic
      stress such as hypoxia, and the influence of GSH on oxidative susceptibility, and
      redox contribution to genesis of gut disorders. The discussion is pertinent to
      understanding dietary lipid peroxides and GSH redox balance in intestinal
      physiology and pathophysiology and the significance of luminal GSH in preserving
      the integrity of the intestinal epithelium.

PMID- 15845422
TI  - Role of glutathione transport processes in kidney function.
AB  - The kidneys are highly dependent on an adequate supply of glutathione (GSH) to
      maintain normal function. This is due, in part, to high rates of aerobic
      metabolism, particularly in the proximal tubules. Additionally, the kidneys are
      potentially exposed to high concentrations of oxidants and reactive
      electrophiles. Renal cellular concentrations of GSH are maintained by both
      intracellular synthesis and transport from outside the cell. Although function of
      specific carriers has not been definitively demonstrated, it is likely that
      multiple carriers are responsible for plasma membrane transport of GSH. Data
      suggest that the organic anion transporters OAT1 and OAT3 and the sodium
      dicarboxylate 2 exchanger (SDCT2 or NaDC3) mediate uptake across the basolateral
      plasma membrane (BLM) and that the organic anion transporting polypeptide OATP1
      and at least one of the multidrug resistance proteins mediate efflux across the
      brush-border plasma membrane (BBM). BLM transport may be used pharmacologically
      to provide renal proximal tubular cells with exogenous GSH to protect against
      oxidative stress whereas BBM transport functions physiologically in turnover of
      cellular GSH. The mitochondrial GSH pool is derived from cytoplasmic GSH by
      transport into the mitochondrial matrix and is mediated by the dicarboxylate and
      2-oxoglutarate exchangers. Maintenance of the mitochondrial GSH pool is critical
      for cellular and mitochondrial redox homeostasis and is important in determining
      susceptibility to chemically induced apoptosis. Hence, membrane transport
      processes are critical to regulation of renal cellular and subcellular GSH pools
      and are determinants of susceptibility to cytotoxicity induced by oxidants and
      electrophiles.

PMID- 15845423
TI  - The importance of glutamate, glycine, and gamma-aminobutyric acid transport and
      regulation in manganese, mercury and lead neurotoxicity.
AB  - Historically, amino acids were studied in the context of their importance in
      protein synthesis. In the 1950s, the focus of research shifted as amino acids
      were recognized as putative neurotransmitters. Today, many amino acids are
      considered important neurochemicals. Although many amino acids play a role in
      neurotransmission, glutamate (Glu), glycine (Gly), and gamma-aminobutyric acid
      (GABA) are among the more prevalent and better understood. Glu, the major
      excitatory neurotransmitter, and Gly and GABA, the major inhibitory
      neurotransmitters, in the central nervous system, are known to be tightly
      regulated. Prolonged exposure to environmental toxicants, such as manganese (Mn),
      mercury (Hg), or lead (Pb), however, can lead to dysregulation of these
      neurochemicals and subsequent neurotoxicity. While the ability of these metals to
      disrupt the regulation of Glu, Gly and GABA have been studied, few articles have
      examined the collective role of these amino acids in the respective metal's
      mechanism of toxicity. For each of the neurotransmitters above, we will provide a
      brief synopsis of their regulatory function, including the importance of
      transport and re-uptake in maintaining their optimal function. Additionally, the
      review will address the hypothesis that aberrant homeostasis of any of these
      amino acids, or a combination of the three, plays a role in the neurotoxicity of
      Mn, Hg, or Pb.

PMID- 15845424
TI  - The dopamine transporter: role in neurotoxicity and human disease.
AB  - The dopamine transporter (DAT) is a plasma membrane transport protein expressed
      exclusively within a small subset of CNS neurons. It plays a crucial role in
      controlling dopamine-mediated neurotransmission and a number of associated
      behaviors. This review focuses on recent data elucidating the role of the
      dopamine transporter in neurotoxicity and a number of CNS disorders, including
      Parkinson disease, drug abuse, and attention deficit hyperactivity disorder
      (ADHD).

PMID- 15845425
TI  - Use of amphotericin B lipid complex in elderly patients.
AB  - OBJECTIVES: The safety and effectiveness of amphotericin B lipid complex (ABLC)
      treatment in elderly patients was investigated using a large multicenter
      database. METHODS: Data analysis was conducted on retrospectively collected
      patient data from 572 patients >65 years of age and 2930 patients < or =65 years
      of age treated for fungal infections at 160 North American hospitals. RESULTS:
      Patients were typically treated with ABLC for Candidiasis, multiple fungal
      pathogen infections and Aspergillosis, or were treated empirically. The median
      cumulative dose of ABLC in patients >65 years of age and those 65 years of age
      was similar (3000 and 3258 mg, respectively, P=0.127). Despite higher median
      pretreatment serum creatinine (S-Cr) among patients >65 years of age (1.7 mg/dl
      vs. 1.4 mg/dl, respectively), both groups showed only a 0.1mg/dl median S-Cr
      change from baseline by the end of therapy (P=0.525). Clinical response was 56
      and 51%, respectively, in patients >65 years of age and patients 65 years of age
      or younger (P=0.049). CONCLUSIONS: This study suggests that ABLC can be safely
      and effectively used in the treatment of invasive fungal disease in elderly
      patients.

PMID- 15845426
TI  - Bacteraemia in the elderly: predictors of outcome in an urban teaching hospital.
AB  - OBJECTIVES: To analyze the underlying factors of mortality in elderly adults with
      bacteraemia. METHODS: The study included 238 episodes of bacteraemia in an urban
      public teaching hospital. Retrospective chart review recorded demographic
      information, comorbid conditions, length of stay, source of infection, and
      physiologic and laboratory data on admission. RESULTS: Of the 238 episodes of
      bacteraemia, 128 patients were 65-74 years of age and 110 patients were > or =75
      years of age. Eighty-one percent came from home. Fifty-four percent had Gram
      positive cocci detected in blood cultures and 36% had Gram negative bacilli.
      Factors associated with increased odds of mortality included underlying renal
      disease, admission to MICU, hypotension and hypoalbuminemia. Decreased odds of
      mortality were associated with being admitted from home and receiving appropriate
      antibiotics. CONCLUSIONS: Bacteraemia in the elderly has a high mortality rate,
      but is not significantly increased in those >or =75 years of age. The recent
      microbiology has shifted from Gram negative bacilli to Gram positive cocci.
      Physiologic abnormalities on admission predict worse outcomes in the elderly
      bacteraemic patient. Hypoalbuminemia on admission is associated with higher
      mortality rates in the elderly.

PMID- 15845419
TI  - Molecular and ionic mimicry and the transport of toxic metals.
AB  - Despite many scientific advances, human exposure to, and intoxication by, toxic
      metal species continues to occur. Surprisingly, little is understood about the
      mechanisms by which certain metals and metal-containing species gain entry into
      target cells. Since there do not appear to be transporters designed specifically
      for the entry of most toxic metal species into mammalian cells, it has been
      postulated that some of these metals gain entry into target cells, through the
      mechanisms of ionic and/or molecular mimicry, at the site of transporters of
      essential elements and/or molecules. The primary purpose of this review is to
      discuss the transport of selective toxic metals in target organs and provide
      evidence supporting a role of ionic and/or molecular mimicry. In the context of
      this review, molecular mimicry refers to the ability of a metal ion to bond to an
      endogenous organic molecule to form an organic metal species that acts as a
      functional or structural mimic of essential molecules at the sites of
      transporters of those molecules. Ionic mimicry refers to the ability of a
      cationic form of a toxic metal to mimic an essential element or cationic species
      of an element at the site of a transporter of that element. Molecular and ionic
      mimics can also be sub-classified as structural or functional mimics. This review
      will present the established and putative roles of molecular and ionic mimicry in
      the transport of mercury, cadmium, lead, arsenic, selenium, and selected
      oxyanions in target organs and tissues.

PMID- 15845427
TI  - Profile and prognosis of febrile elderly patients with bacteremic urinary tract
      infection.
AB  - OBJECTIVE: To describe the profile of elderly patients with bacteremic urinary
      tract infections (UTI) and correlate clinical and laboratory findings with the
      outcome in order to identify independent predictors of mortality. METHODS: This
      retrospective study took place in a large community-based, geriatric hospital and
      included 191 patients aged 75-105 years with urine and blood cultures
      simultaneously positive for bacterial organisms. Records were analysed for
      demographic information, clinical and laboratory data over a 29 month period.
      Mortality was assessed and was correlated with these findings. RESULTS: Most of
      the patients (80.1%) had community-acquired infection. Gram-negative organisms
      accounted for 87.6% of bacterial isolates, with Escherichia coli accounting for
      46.1% of cases. Non-Escherichia coli Gram-negative organisms were highly
      resistant to two common urinary tract antibiotics (gentamicin and ceftriaxone).
      Patients with chronic urinary catheter had Gram-negative bacteria significantly
      less sensitive to ciprofloxacin, gentamycin, ampicillin and ceftriaxon than
      patients without catheter (p<0.05). In-hospital mortality was 33%. Multiple
      logistic regression analysis revealed that mortality was significantly related to
      the number of underlying diagnoses (p<0.0203), cognitive status (p<0.0003),
      length of hospitalization (p<0.0397), low level of serum albumin (p<0.0021), high
      neutrophil count (p<0.0001) and high level of lactate dehydrogenase (p<0.0351).
      Fatality was not associated with advanced age in the very old. CONCLUSION:
      Bacteremic UTI in the elderly has a high mortality rate. In frail elderly
      patients with age-associated multiple severe underlying disorders and cognitive
      impairment, early recognition of bacteremic UTI and prompt, appropriate treatment
      are critical in reducing the mortality.

PMID- 15845428
TI  - Drug resistance of Mycobacterium tuberculosis in Western Turkey: a retrospective
      study from 1100-bed teaching hospital.
AB  - OBJECTIVE: This study was planned to establish resistance profile of
      Mycobacterium tuberculosis strains in the West part of Turkey. METHODS: The data
      were collected by searching records of tuberculosis (TB) division of microbiology
      laboratory in 1999 and 2001, retrospectively. RESULTS: Susceptibilities of the
      all first-line anti-TB drugs ratio were 76% in 1999 and 83.5% in 2001. Drug
      resistance of against isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and
      streptomycin (SM) were detected 11.9, 10.2, 11.92, 10.88% and 9.9, 9.27, 6.36,
      8.56% for 1999 and 2001, respectively. Multidrug resistance (MDR)-TB rate was
      found on the high level (6.6 and 5.8%). CONCLUSIONS: It was thought that
      resistance rates of M. tuberculosis strains should be followed regularly and
      reasons for the high rates should be investigated. It was concluded that
      development of the national TB policy was the main issue for solving the present
      problems dealing with management of TB. SUMMARY: M. tuberculosis is one of the
      important emerging pathogens. Multidrug and polidrug strains have been increasing
      around the world. This study was planned to define drug resistance patterns for
      monitoring drug-resistant TB in Western Turkey. It is suggested that a close
      collaboration between academic researchers and TB system workers would be
      organized for further studies.

PMID- 15845429
TI  - Virulence characteristics of Escherichia coli strains causing acute cystitis in
      young adults in Iran.
AB  - BACKGROUND: Escherichia coli strains that cause cystitis posses virulence
      properties that facilitate their colonisation and persistence in the bladder. In
      Iran, despite the high number of the urinary tract infections, very few studies
      has been done to determine the role of these virulence properties in the
      pathogenesis of E. coli cyctitis. PATIENTS AND METHODS: Eighty-seven strains of
      E. coli, isolated from young adults with cystitis in Shiraz, Iran, were examined
      for the expression of type 1 and P-fimbriae, mannose resistant haemagglutination,
      haemolysin production, aerobactin-mediated iron uptake, O:K serotypes,
      biochemical phenotypes (BPTs) and their antibiotic susceptibility patterns.
      RESULTS: Seventy-six percent of the strains expressed multiple virulence
      properties. There was a significant correlation between the presence of
      aerobactin and the expression of type 1 fimbriae. All P-fimbriated strains
      produced aerobactin with 50% of them also coexpressing haemolysin. Of the 29
      different O:K serotypes identified, 42% belonged to serotypes not commonly found
      among European serotypes associated with UTI. Strains of O groups 4 and 6
      expressed more virulence factors than the others. A high resistance against
      ampicillin, trimethoprim and cotrimoxasol was observed among the isolates with
      53% of the isolates showing multiresistance to these three antibiotics. Certain
      BPTs were also found among O:K serotypes with some containing strains of the same
      virulence profile. CONCLUSION: We conclude that certain colonal groups of E. coli
      are commonly associated with cystitis in young adults in Iran with strains
      possessing a combination of aerobactin and type 1 fimbriae being the dominant
      ones and belonging to serotypes not commonly found in Europe. We also conclude
      that the multiple antibiotic resistant E. coli strains causing cyctitis are
      highly prevalent in this part of the country.

PMID- 15845430
TI  - Respiratory viral infections in patients with chronic, obstructive pulmonary
      disease.
AB  - OBJECTIVES: The purpose of the present study was to apply reverse transcription
      PCR (RT-PCR) assays to clinical specimens collected from patients with acute
      respiratory illness and chronic obstructive pulmonary disease (COPD). METHODS:
      One hundred and ninety-four samples from two different study cohorts were
      analysed using RT-PCR assays for picornaviruses, coronaviruses 229E and OC43,
      influenza A and B viruses, respiratory syncytial virus, parainfluenza types 1-3
      viruses, and human metapneumovirus and a PCR assay for adenoviruses. The results
      were added to results obtained previously using cell culture and serologic
      methods. RESULTS: RT-PCR assays identified an additional 35 respiratory virus
      associated illnesses not identified previously by cell culture or serology
      (n=46). Picornaviruses and coronaviruses were the most common viral infections
      identified only by RT-PCR. Overall, 41.8% of the acute respiratory illnesses
      evaluated were associated with a respiratory virus infection, with
      picornaviruses, coronaviruses and influenza viruses being the most common
      infections recognized. No human metapneumovirus infections were identified by RT
      PCR assay. CONCLUSIONS: Respiratory viral infections are commonly associated with
      acute respiratory illness in COPD patients, and the use of RT-PCR assays
      significantly increases the ability to diagnose these infections.

PMID- 15845431
TI  - Prevalence of diabetes mellitus and dyslipidemia among antiretroviral naive
      patients co-infected with hepatitis C virus (HCV) and HIV-1 compared to patients
      without co-infection.
AB  - OBJECTIVE: An increased prevalence of type 2 diabetes mellitus (DM) has been
      associated with HCV in the non-HIV infected populations. To describe a similar
      association among HIV subjects, and explore the biological mechanisms. METHODS:
      In a cross-sectional analysis, we compared the prevalence of DM (using American
      Diabetes Association criteria) and insulin resistance (HOMA IR) and dyslipidemia
      among ARV naive patients with HIV and HIV/HCV infected patients enrolled in CPCRA
      FIRST (058) and the Metabolic Substudy (061). RESULTS: Among 1389 enrolled in the
      FIRST study and had HCV serology, the prevalence of diabetes was higher (5.9%)
      among HCV/HIV as compared to 3.3% among those with HIV alone (p=0.04). Among 417
      enrolled in the metabolic substudy, 88 (21%) had HIV/HCV co-infection. As in the
      main study, the prevalence of DM was higher in HIV/HCV group (9 vs. 3%, p=0.03).
      The HIV/HCV infected were significantly older (43 vs. 37 years), non-white (83
      vs. 70%), with a history of IDU (55 vs. 3%), had higher AST (61 vs. 39 U/l), ALT
      (55 vs. 43 U/l,) and lower cholesterol levels (3.97 vs. 4.25 mmol/l). By
      multivariate analysis among subjects <50 years, association between HCV and
      diabetes remained significant after adjusting for BMI, family history of diabetes
      (OR=3.7, 95% CI: 1.3-11.1, p=0.02). The insulin resistance (HOMA IR) was not
      different between the two groups, however, the prevalence of dyslipidemia was
      lower among HCV co-infected subjects. CONCLUSIONS: Subjects with HIV/HCV co
      infection have a higher prevalence of diabetes and thus may need to be screened
      for it prior to initiation of anti-retroviral therapy, particularly if it is a PI
      based regimen.

PMID- 15845432
TI  - Corynebacterium striatum: an underappreciated community and nosocomial pathogen.
AB  - Corynebacterium striatum (CS) is an underappreciated human pathogen that has been
      associated with serious infections in both immunocompetent and immunocompromised
      hosts. CS infections tend to be more frequent in males and major infection sites
      have included blood stream, lung, and central nervous system. Most are
      nosocomially acquired and there is a significant association with medical devices
      ranging from intravascular catheters to central nervous system drainage devices.
      Empiric therapy with vancomycin is advisable as susceptibility to other agents is
      variable. Treatment may also include removal of foreign material such as an
      intravascular catheter. The present review describes the wide spectrum of
      infections associated with CS and we add a unique case of CS pancreatic abscess
      where treatment included linezolid.

PMID- 15845433
TI  - Pasteurella multocida meningitis: case report and review of the literature.
AB  - Pasteurella multocida forms part of the normal flora in the nasopharynx of many
      domestic and wild animals. Most human P. multocida infections are soft tissue
      infections due to animal bites. P. multocida meningitis is a rare condition. We
      report a case of P. multocida meningitis with a complicated outcome and review
      the literature of this condition.

PMID- 15845434
TI  - An unusual case of pericarditis caused by Cardiobacterium hominis.

PMID- 15845435
TI  - Cure of post-traumatic recurrent multiresistant Gram-negative rod meningitis with
      intraventricular colistin.
AB  - A 28-year-old man developed five episodes of meningitis, all due to
      multiresistant Gram-negative rods during his 7-month hospitalisation after head
      trauma. This patient's recurrent meningitis was solved only when colistin and
      amikacin were given by the intraventricular in addition to the intravenous route
      for a long period of time, specifically 6 weeks.

PMID- 15845436
TI  - Facklamia hominis causing chorioamnionitis and puerperal bacteraemia.

PMID- 15845437
TI  - Listeria monocytogenes skin infection with cerebritis and haemophagocytosis
      syndrome in a bone marrow transplant recipient.
AB  - In this report, we describe unusual and unreported manifestations of Listeria
      monocytogenes infection in a bone marrow transplant recipient, including
      cutaneous infection with an hamophagocytosis syndrome and cerebritis. L.
      monocytogenes occurred despite a broad spectrum antibiotherapy. L. monocytogenes
      was isolated from a skin biopsy. Outcome was favorable with amoxicillin and
      gentamicin therapy. L. monocytogenes infection should be suspected in patients
      with cerebritis despite large spectrum antibiotherapy and this report underscores
      the usefulness of skin biopsies in febrile immunocompromised patients.

PMID- 15845438
TI  - Actinomyces viscosus endocarditis requiring aortic valve replacement.
AB  - We report a case of primary Actinomyces viscosus endocarditis, an unusual
      manifestation of actinomycosis, in a 43-year-old farmer with an indolent febrile
      illness. As has occurred in previous cases, diagnosis was delayed in part because
      blood isolates were misidentified. Months later when she required aortic valve
      and root replacement, histologic exam of the diseased valve revealed branching
      filamentous organisms and the original blood isolates were retrospectively
      confirmed to be Actinomyces viscosus.

PMID- 15845439
TI  - Crimean Congo hemorrhagic fever infection simulating acute appendicitis.
AB  - An unusual cause of acute abdominal pain simulating acute appendicitis is
      presented. The patient was admitted with complaints of fever, malaise, headache,
      nausea, vomiting, diarrhoea, and severe bleeding. Based on the clinical and
      epidemiological findings, a diagnosis of Crimean Congo hemorrhagic fever virus
      infection was suspected, and ribavirin therapy was started. While her clinical
      condition was improving, she experienced a sudden pain at her right lower
      quadrant of the abdomen. Explorative laparotomy revealed haemorrhage within the
      abdominal muscles. Her CCHF IgM was found to be positive.

PMID- 15845440
TI  - Sudden death from human parainfluenza virus 2.

PMID- 15845441
TI  - Licensed viral vaccines.

PMID- 15845442
TI  - Is torquetenovirus a potential cause of liver damage in children?

PMID- 15845443
TI  - Reactivation of brucellosis after treatment with infliximab in a patient with
      rheumatoid arthritis.

PMID- 15845444
TI  - "Sweet talk": closing in on C type lectin signaling.
AB  - C type lectins recognize pathogens by binding to pathogen-specific carbohydrate
      residues. The finding reported by Rogers et al. (2005) in this issue of Immunity,
      that ligand binding by the C type lectin Dectin-1 leads to recruitment of the
      tyrosine kinase Syk and is critical to subsequent cytokine production by the
      cell, will surely inspire further research on the mechanisms of carbohydrate
      receptor signaling.

PMID- 15845445
TI  - NF-kappa B comes home.
AB  - NF-kappa B was discovered because of its binding to the Ig kappa locus intronic
      enhancer, but deletion of its binding site does not appear to affect V-to-J kappa
      rearrangement. New work by Verkoczy et al. in this issue of Immunity suggests
      that NF-kappa B regulates Ig kappa rearrangement after all, by activating RAG
      expression during receptor editing.

PMID- 15845446
TI  - Gene modification strategies to induce tumor immunity.
AB  - The immune system provides an attractive option for use in cancer therapy. Our
      increasing understanding of the molecular events important in the generation of
      an effective immune response presents us with the opportunity to manipulate key
      genes to boost the immune response against cancer. Genetic modification is being
      employed to enhance a range of immune processes including antigen presentation,
      activation of specific T cells, and localization of immune effectors to tumors.
      In this review, we describe how many diverse cell types, including dendritic
      cells, T cells, and tumor cells, are being modified with a variety of genes,
      including those encoding antigens, cytokines, and chemokines, in order to enhance
      tumor immunity.

PMID- 15845447
TI  - C5a negatively regulates toll-like receptor 4-induced immune responses.
AB  - The complement system and the Toll-like receptors (TLRs) are two central arms of
      innate immunity that are critical to host defense as well as the development of
      adaptive immunity. Most pathogens activate both complement and TLRs, suggesting
      the potential for crosstalk between the two systems. We show here that the
      complement-derived C5a anaphylatoxin negatively regulates TLR4- and CD40-induced
      synthesis of IL-12 family cytokines (IL-12, IL-23, and IL-27) from inflammatory
      macrophages (M phi s) by extracellular signal-regulated kinase- and
      phosphoinositide 3 kinase-dependent pathways. This decreased cytokine response
      translates into a decreased T helper type 1 (Th1) response in vitro and in vivo.
      Accordingly, we found enhanced Th1 immunity in C5a receptor-deficient mice,
      something that conferred protection from Leishmania major infection. Our findings
      identify the negative impact of C5a on IL-12 family cytokines as an important
      mechanism for regulating Th1 polarization in response to innate and adaptive
      immune network activation.

PMID- 15845448
TI  - Convergence on a distinctive assembly mechanism by unrelated families of
      activating immune receptors.
AB  - Activating receptors in cells of hematopoetic origin include members of two
      unrelated protein families, the immunoglobulin (Ig) and C type lectins, which
      differ even in the orientation of the transmembrane (TM) domains. We examined
      assembly of four receptors with diverse function: the NK receptors KIR2DS and
      NKG2C/CD94, the Fc receptor for IgA, and the GPVI collagen receptor. For each of
      the four different receptors studied here, assembly results in the formation of a
      three-helix interface in the membrane involving two acidic TM residues from the
      signaling dimer and a basic TM residue from the ligand recognition module, an
      arrangement remarkably similar to the T cell receptor (TCR)-CD3 complex. The fact
      that the TM domains of Ig family and C type lectins adopt opposite orientations
      proves that these receptor families independently evolved toward the same
      structural arrangement of the interacting TM helices. This assembly mechanism is
      thus widely utilized by receptors in cells of hematopoetic origin.

PMID- 15845449
TI  - Intrinsic lymphotoxin-beta receptor requirement for homeostasis of lymphoid
      tissue dendritic cells.
AB  - The factors regulating dendritic cell (DC) development and homeostasis are
      incompletely understood. Here, we demonstrate that DCs express the lymphotoxin
      (LT)-beta receptor (LT beta R) and that in mice lacking the LT beta R in
      hematopoietic cells, spleen, and lymph node, CD8- DC numbers are reduced. B cells
      are a key source of LT alpha 1 beta 2 for splenic DC homeostasis, and transgenic
      overexpression of LT alpha 1 beta 2 on B cells leads to expansion of the CD8- DC
      compartment. Furthermore, we find that about 5% of splenic DCs are undergoing
      cell division, and the number of dividing CD8- DCs is disproportionately reduced
      in the absence of the LT beta R. In parabiosis experiments, splenic DCs were only
      partially replaced by circulating precursors over a 6 week period. We conclude
      that LT alpha 1 bet a2 acts on DCs or DC precursors to promote DC homeostasis,
      and we suggest that DC proliferation is an important pathway for locally
      maintaining these cells in the steady state.

PMID- 15845450
TI  - Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase
      C gamma 2 that specifically increases external Ca2+ entry.
AB  - The identification of specific genetic loci that contribute to inflammatory and
      autoimmune diseases has proved difficult due to the contribution of multiple
      interacting genes, the inherent genetic heterogeneity present in human
      populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea
      (ENU) mutagenesis to discover new immune regulators, we identified a point
      mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe
      spontaneous inflammation and autoimmunity. The disease is composed of an
      autoimmune component mediated by autoantibody immune complexes and B and T cell
      independent inflammation. The underlying mechanism is a gain-of-function mutation
      in Plcg2, which leads to hyperreactive external calcium entry in B cells and
      expansion of innate inflammatory cells. This mutant identifies Plcg2 as a key
      regulator in an autoimmune and inflammatory disease mediated by B cells and non
      B, non-T haematopoietic cells and emphasizes that by distinct genetic modulation,
      a single point mutation can lead to a complex immunological phenotype.

PMID- 15845451
TI  - Upon TLR9 signaling, CD5+ B cells control the IL-12-dependent Th1-priming
      capacity of neonatal DCs.
AB  - The susceptibility to infections and the strong Th2 bias observed in neonates are
      thought to be due to the immaturity of the dendritic cell (DC) compartment. We
      show that neonatal DCs, like their adult counterparts, elicit Th1 responses. We
      also demonstrate that during potentially harmful systemic inflammation, after
      Toll-like receptor (TLR) 9 triggering, neonatal B cells produce high
      concentrations of IL-10, preventing optimal IL-12 secretion by neonatal DCs and,
      thus, Th1 priming. Although both CD5+ and CD5- B cell subsets respond to CpG ODN
      stimulation, we found that only CD5+ B cells produce IL-10. Therefore, these
      results show the regulatory role of CD5+ B cells on DC activation in vivo for
      Th1/Th2 polarization and highlight the paradoxical effects of TLR triggering in
      vivo.

PMID- 15845452
TI  - Stroma-mediated dysregulation of myelopoiesis in mice lacking I kappa B alpha.
AB  - Hematopoiesis occurs in the liver and the bone marrow (BM) during murine
      development. Newborn mice with a ubiquitous deletion of I kappa B alpha develop a
      severe hematological disorder characterized by an increase of
      granulocyte/erythroid/monocyte/macrophage colony-forming units (CFU-GEMM) and
      hypergranulopoiesis. Here, we report that this particular myeloproliferative
      disturbance is mediated by continuously deregulated perinatal expression of
      Jagged1 in I kappa B alpha-deficient hepatocytes. The result is a permanent
      activation of Notch1 in neutrophils. In contrast, in mice with a conditional
      deletion of I kappa B alpha only in the myeloid lineage (ikba(flox/flox) x LysM
      Cre) and in fetal liver cell chimeras (ikba(FL delta/FL delta)), a cell
      autonomous induction of the myeloproliferative disease was not observed.
      Coculture of I kappa B alpha-deficient hepatocytes with wild-type (wt) BM cells
      induced a Jagged1-dependent increase in CFUs. In summary, we show that cell-fate
      decisions leading to a premalignant hematopoietic disorder can be initiated by
      nonhematopoietic cells with inactive I kappa B alpha.

PMID- 15845453
TI  - CCL19 and CCL21 induce a potent proinflammatory differentiation program in
      licensed dendritic cells.
AB  - Dendritic cells (DCs) are key instigators of adaptive immune responses. Using an
      alphaviral expression cloning technology, we have identified the chemokine CCL19
      as a potent inducer of T cell proliferation in a DC-T cell coculture system.
      Subsequent studies showed that CCL19 enhanced T cell proliferation by inducing
      maturation of DCs, resulting in upregulation of costimulatory molecules and the
      production of proinflammatory cytokines. Moreover, CCL19 programmed DCs for the
      induction of T helper type (Th) 1 rather than Th2 responses. Importantly, only
      activated DCs that migrated from the periphery to draining lymph nodes, but not
      resting steady-state DCs residing within lymph nodes, expressed high levels of
      CCR7 in vivo and responded to CCL19 with the production of proinflammatory
      cytokines. Migrating DCs isolated from mice genetically deficient in CCL19 and
      CCL21 (plt/plt) presented an only partially mature phenotype, highlighting the
      importance of these chemokines for full DC maturation in vivo. Our findings
      indicate that CCL19 and CCL21 are potent natural adjuvants for terminal
      activation of DCs and suggest that chemokines not only orchestrate DC migration
      but also regulate their immunogenic potential for the induction of T cell
      responses.

PMID- 15845454
TI  - Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition
      pathway for C type lectins.
AB  - Pattern-recognition receptors (PRRs) detect molecular signatures of microbes and
      initiate immune responses to infection. Prototypical PRRs such as Toll-like
      receptors (TLRs) signal via a conserved pathway to induce innate response genes.
      In contrast, the signaling pathways engaged by other classes of putative PRRs
      remain ill defined. Here, we demonstrate that the beta-glucan receptor Dectin-1,
      a yeast binding C type lectin known to synergize with TLR2 to induce TNF alpha
      and IL-12, can also promote synthesis of IL-2 and IL-10 through phosphorylation
      of the membrane proximal tyrosine in the cytoplasmic domain and recruitment of
      Syk kinase. syk-/- dendritic cells (DCs) do not make IL-10 or IL-2 upon yeast
      stimulation but produce IL-12, indicating that the Dectin-1/Syk and Dectin-1/TLR2
      pathways can operate independently. These results identify a novel signaling
      pathway involved in pattern recognition by C type lectins and suggest a potential
      role for Syk kinase in regulation of innate immunity.

PMID- 15845456
TI  - The phylogenetic positions of three Basal-hexapod groups (protura, diplura, and
      collembola) based on ribosomal RNA gene sequences.
AB  - This study combined complete 18S with partial 28S ribosomal RNA gene sequences (
      approximately 2,000 nt in total) to investigate the relations of basal hexapods.
      Ten species of Protura, 12 of Diplura, and 10 of Collembola (representing all
      subgroups of these three clades) were sequenced, along with 5 true insects and 8
      other arthropods, which served as out-groups. Trees were constructed with maximum
      parsimony, maximum likelihood, Bayesian analysis, and minimum-evolution analysis
      of LogDet-transformed distances. All methods yielded strong support for a clade
      of Protura plus Diplura, here named Nonoculata, and for monophyly of the Diplura.
      Parametric-bootstrapping analysis showed our data to be inconsistent with
      previous hypotheses (P < 0.01) that joined Protura with Collembola (Ellipura),
      that said Diplura are sister to true insects or are diphyletic, and that said
      Collembola are not hexapods. That is, our data are consistent with hexapod
      monophyly and Collembola grouped weakly with "Protura + Diplura" under most
      analytical conditions. As a caveat to the above conclusions, the sequences showed
      nonstationarity of nucleotide frequencies across taxa, so the CG-rich sequences
      of the diplurans and proturans may have grouped together artifactually; however,
      the fact that the LogDet method supported this group lessens this possibility.
      Within the basal hexapod groups, where nucleotide frequencies were stationary,
      traditional taxonomic subgroups generally were recovered: i.e., within Protura,
      the Eosentomata and Acerentomata (but Sinentomata was not monophyletic); within
      Collembola, the Arthropleona, Poduromorpha, and Entomobryomorpha (but
      Symphypleona was polyphyletic); and in Diplura, the most complete data set (>
      2,100 nt) showed monophyly of Campodeoidea and of Japygoidea, and most methods
      united Projapygoidea with Japygoidea.

PMID- 15845455
TI  - A role for nuclear factor kappa B/rel transcription factors in the regulation of
      the recombinase activator genes.
AB  - In developing B cells, expression of surface immunoglobulin is an important
      signal to terminate recombinase activator gene (RAG) expression and V(D)J
      recombination. However, autoreactive antigen receptors instead promote continued
      gene rearrangement and receptor editing. The regulation by B cell receptor (BCR)
      signaling of RAG expression and editing is poorly understood. We report that in
      editing-competent cells BCR ligand-induced RAG mRNA expression is regulated at
      the level of RAG transcription, rather than mRNA stability. In immature B cells
      carrying innocuous receptors, RAG expression appears to be under rapidly
      reversible negative regulation. Studies involving transduction of a
      superrepressive (sr) I kappa B alpha protein indicate that NF-kappaB/Rel proteins
      promote RAG transcription. Interestingly, NF kappa B1-deficient cells overexpress
      RAG and undergo an exaggerated receptor editing response. Our data implicate NF
      kappa B transcription factors in the BCR-mediated regulation of RAG locus
      transcription. Rapidly activated NF kappa B pathways may facilitate prompt
      antigen receptor-regulated changes in RAG expression important for editing and
      haplotype exclusion.

PMID- 15845457
TI  - A role for CD103 in the retention of CD4+CD25+ Treg and control of Leishmania
      major infection.
AB  - Endogenous regulatory T cells (T(reg)) play a central role in the control of
      excessive or misdirected immune responses against self or foreign Ags. To date,
      virtually no data are available on the nature of the molecules and signals
      involved in the trafficking and retention of T(reg) in tissues where regulation
      is required. Here, we show that expression of alpha(E)beta(7) integrin is
      necessary for the homing of T(reg) at site of Leishmania major infection. The
      vast majority of T(reg) present in the dermis at steady-state conditions or
      during L. major infection express the alpha(E) chain (CD103) of alpha(E)beta(7).
      Genetically susceptible BALB/c mice that lack CD103 become resistant to
      infection, a phenotype that is associated with a poor capacity of T(reg) to be
      retained in the infected site. Such susceptible phenotype can be restored when
      T(reg) from wild-type mice were transferred in CD103(-/-) mice. The central role
      of CD103 in T(reg) retention was further demonstrated by usage of blocking Abs
      against CD103 and the transfer of T(reg) purified from CD103(-/-) mice. Our
      results strongly suggest that this molecule is induced and maintained on T(reg)
      following or just prior to their arrival in tissues. Furthermore, the expression
      of CD103 and the subsequent retention of T(reg) in tissues is highly regulated by
      their exposure to Leishmania Ag and the level of activation of the APCs they
      encounter. Thus, CD103, by controlling T(reg) retention, can contribute to the
      outcome of chronic infection by Leishmania.

PMID- 15845458
TI  - Chemical xenobiotics and mitochondrial autoantigens in primary biliary cirrhosis:
      identification of antibodies against a common environmental, cosmetic, and food
      additive, 2-octynoic acid.
AB  - Emerging evidence has suggested environmental factors as causative agents in the
      pathogenesis of primary biliary cirrhosis (PBC). We have hypothesized that in PBC
      the lipoyl domain of the immunodominant E2 component of pyruvate dehydrogenase
      (PDC-E2) is replaced by a chemical xenobiotic mimic, which is sufficient to break
      self-tolerance. To address this hypothesis, based upon our quantitative structure
      activity relationship data, a total of 107 potential xenobiotic mimics were
      coupled to the lysine residue of the immunodominant 15 amino acid peptide of the
      PDC-E2 inner lipoyl domain and spotted on microarray slides. Sera from patients
      with PBC (n = 47), primary sclerosing cholangitis (n = 15), and healthy
      volunteers (n = 20) were assayed for Ig reactivity. PBC sera were subsequently
      absorbed with native lipoylated PDC-E2 peptide or a xenobiotically modified PDC
      E2 peptide, and the remaining reactivity analyzed. Of the 107 xenobiotics, 33 had
      a significantly higher IgG reactivity against PBC sera compared with control
      sera. In addition, 9 of those 33 compounds were more reactive than the native
      lipoylated peptide. Following absorption, 8 of the 9 compounds demonstrated cross
      reactivity with lipoic acid. One compound, 2-octynoic acid, was unique in both
      its quantitative structure-activity relationship analysis and reactivity. PBC
      patient sera demonstrated high Ig reactivity against 2-octynoic acid-PDC-E2
      peptide. Not only does 2-octynoic acid have the potential to modify PDC-E2 in
      vivo but importantly it was/is widely used in the environment including perfumes,
      lipstick, and many common food flavorings.

PMID- 15845460
TI  - Modulation of host cytoskeleton function by the enteropathogenic Escherichia coli
      and Citrobacter rodentium effector protein EspG.
AB  - EspG is a conserved protein encoded by the locus of enterocyte effacement (LEE)
      of attaching and effacing (A/E) pathogens, including enteropathogenic and
      enterohemorrhagic Escherichia coli and Citrobacter rodentium. EspG is delivered
      into infected host cells by a type III secretion system. The role of EspG in
      virulence has not yet been defined. Here we describe experiments that probe the
      virulence characteristics and biological activities of EspG in vitro and in vivo.
      A C. rodentium espG mutant displayed a significantly reduced ability to colonize
      C57BL/6 mice and to cause colonic hyperplasia. Epitope-tagged EspG was detected
      in the apical regions of infected colonic epithelial cells in infected mice,
      partially localizing with another LEE-encoded effector protein, Tir. EspG was
      found to interact with mammalian tubulin in both genetic screens and gel overlay
      assays. Binding to tubulin by EspG caused localized microtubule depolymerization,
      resulting in actin stress fiber formation through an undefined mechanism.
      Heterologous expression of EspG in yeast resulted in loss of cytoplasmic
      microtubule structure and function, preventing coordination between bud
      development and nuclear division. Yeast expressing EspG were also unable to
      control cortical actin polarity. We suggest that EspG contributes to the ability
      of A/E pathogens to establish infection through a modulation of the host
      cytoskeleton involving transient microtubule destruction and actin polymerization
      in a manner akin to the Shigella flexneri VirA protein.

PMID- 15845459
TI  - Enteropathogenic and enterohemorrhagic Escherichia coli infections:
      translocation, translocation, translocation.

PMID- 15845461
TI  - Survival and replication of clinical Mycobacterium tuberculosis isolates in the
      context of human innate immunity.
AB  - The initial host response to Mycobacterium tuberculosis is driven by innate
      immunity. For this study, we examined the ability of 18 recent clinical isolates
      and 5 reference strains to survive and replicate in the context of host innate
      immunity by using whole blood culture. Six healthy tuberculin-negative volunteers
      served as subjects. H(37)Ra showed the least capacity to replicate of any of the
      strains tested, decreasing in viability 1.3 log CFU during 72 h of whole blood
      culture, whereas H(37)Rv increased 0.32 log. Clinical isolates varied greatly in
      their ability to replicate in blood cells, ranging from -0.4 to +0.8 log (P <
      0.001). Four showed significantly more growth than H(37)Rv, and one showed
      significantly reduced growth. Host mechanisms for restricting intracellular
      mycobacterial growth were more effective during the first 24 h of whole blood
      culture than during the 24- to 72-h period. Certain mycobacterial isolates
      appeared preferentially able to withstand host defenses during each of these
      intervals. Although there was relatively more homogeneity among subjects than
      among strains, one of the six subjects showed a reduced capacity to restrict
      intracellular mycobacterial growth due to a defect expressed during the first 24
      h of culture. Our findings indicate substantial variability in the capacity of
      clinical tuberculosis isolates to replicate in host cells in the face of innate
      host immunity.

PMID- 15845462
TI  - Trichomonas vaginalis polyamine metabolism is linked to host cell adherence and
      cytotoxicity.
AB  - Trichomonas vaginalis secretes putrescine that is readily detected in vaginal
      secretions. We wanted to examine the effect of decreased putrescine synthesis by
      inhibition of ornithine decarboxylase (ODC) on T. vaginalis. One reason is
      because inhibition of Tritrichomonas foetus ODC results in growth arrest,
      destruction of hydrogenosomes, and decreased amounts of hydrogenosomal enzymes.
      Treatment of T. vaginalis T016 with >/=20 mM 1,4-diamino-2-butanone (DAB) to
      inhibit ODC resulted in growth arrest, which was reversed by addition of
      exogenous putrescine. No similar reversal of growth arrest was achieved with the
      polyamines spermine or spermidine or with iron. Electron microscopic examination
      of control versus DAB-treated trichomonads did not reveal any adverse effects on
      the number and integrity of hydrogenosomes. Further, the adhesins AP65, AP51, and
      AP33 mediating binding to immortalized vaginal epithelial cells (VECs) share
      identity to enzymes of the hydrogenosome organelle, and there was no difference
      in amounts of adhesins between control versus DAB-treated T. vaginalis parasites.
      Likewise, similar patterns and extent of fluorescence were evident for the
      prominent AP65 adhesin. Surprisingly, DAB treatment increased by 4- to 20-fold
      above untreated trichomonads handled identically the level of adherence mediated
      by adhesins. Interestingly, the enhanced attachment to VECs was reversed by
      exogenous putrescine added to DAB-treated trichomonads. Equally noteworthy was
      that DAB-treated T. vaginalis with enhanced adherence did not possess the
      previously reported ability to kill host cells in a contact-dependent fashion
      mediated by cysteine proteinases, and total cysteine proteinase activity patterns
      were identical between control and DAB-treated trichomonads. Overall, these data
      suggest that polyamine metabolism and secreted putrescine are linked to host cell
      adherence and cytotoxicity.

PMID- 15845463
TI  - Molecular cloning and characterization of three beta-defensins from canine
      testes.
AB  - Mammalian beta-defensins are small cationic peptides possessing broad
      antimicrobial and physiological activities. Because dogs are particularly
      resilient to sexually transmitted diseases, it has been proposed that their
      antimicrobial peptide repertoire might provide insight into novel antimicrobial
      therapeutics and treatment regimens. To investigate this proposal, we cloned the
      full-length cDNA of three canine beta-defensin isoforms (cBD-1, -2, and -3) from
      canine testicular tissues. Their predicted peptides share identical N-terminal 65
      amino-acid residues, including the beta-defensin consensus six-cysteine motif.
      The two longer isoforms, cBD-2 and -3, possess 4 and 34 additional amino acids,
      respectively, at the C terminus. To evaluate the antimicrobial activity of cBD, a
      34-amino-acid peptide derived from the shared mature peptide region was
      synthesized. Canine beta-defensin displayed broad antimicrobial activity against
      gram-positive bacteria (Listeria monocytogenes and Staphylococcus aureus; MICs of
      6 and 100 mug/ml, respectively), gram-negative bacteria (Escherichia coli,
      Klebsiella pneumoniae, and Neisseria gonorrhoeae; MICs of 20 to 50, 20, and 50
      mug/ml, respectively), and yeast (Candida albicans; MIC of 5 to 50 mug/ml) and
      lower activity against Ureaplasma urealyticum and U. canigenitalium (MIC of 200
      mug/ml). Antimicrobial potency was significantly reduced at salt concentrations
      higher than 140 mM. All three canine beta-defensins were highly expressed in
      testis. In situ hybridization indicated that cBD-1 was expressed primarily in
      Sertoli cells within the seminiferous tubules. In contrast, cBD-2 was located
      primarily within Leydig cells. The longest isoform, cBD-3, was detected in
      Sertoli cells and to a lesser extent in the interstitium. The tissue-specific
      expression and broad antimicrobial activity suggest that canine beta-defensins
      play an important role in host defense and other physiological functions of the
      male reproductive system.

PMID- 15845464
TI  - CD4+ T cells but Not CD8+ or gammadelta+ lymphocytes are required for host
      protection against Mycobacterium avium infection and dissemination through the
      intestinal route.
AB  - Disseminated Mycobacterium avium infection is common in AIDS patients that do not
      receive anti-AIDS therapy and in patients for whom therapy fails. M. avium is
      commonly acquired by ingestion, and a large number of AIDS patients have M. avium
      in their intestinal tracts. To better understand the dynamics of the infection in
      patients with AIDS, we studied orally infected mice. To determine if
      immunocompetent mice challenged orally with M. avium can develop protection
      against the infection, and if so, which cell population(s) is responsible for the
      protection, we exposed wild-type as well as CD4(-/-), CD8(-/-), and gammadelta(-/
      ) knockout mice to low concentrations of M. avium strain 101 given orally,
      followed by treatment with azithromycin. After 1 month, the mice were challenged
      with kanamycin-resistant M. avium 104. Only CD4(+) T cells appeared to be
      required for protection against the second challenge. Both CD4(+) and CD8(+) T
      cells produced comparable amounts of gamma interferon after the first exposure to
      the bacterium. Tumor necrosis factor alpha was elevated in CD4(+) T cells but not
      in CD8(+) T cells. Following exposure to a small inoculum of mycobacteria orally,
      wild-type mice did not develop disseminated infection for approximately 4 months,
      although viable bacteria could be observed in the mesenteric lymph nodes. The
      ingestion of small numbers of M. avium cells induces a protective immune response
      in the intestines against subsequent infection. However, the bacteria remain
      viable in intestinal lymph nodes and might disseminate later.

PMID- 15845465
TI  - Microarray and proteomics analyses of human intestinal epithelial cells treated
      with the Aeromonas hydrophila cytotoxic enterotoxin.
AB  - We performed microarray analyses on RNA from human intestinal epithelial (HT-29)
      cells treated with the cytotoxic enterotoxin (Act) of Aeromonas hydrophila to
      examine global cellular transcriptional responses. Based on three independent
      experiments, Act upregulated the expression of 34 genes involved in cell growth,
      adhesion, signaling, immune responses (including interleukin-8 [IL-8]
      production), and apoptosis. We verified the upregulation of 14 genes by real-time
      reverse transcriptase-PCR and confirmed Act-induced production of IL-8 by enzyme
      linked immunosorbent assay on supernatants from nonpolarized and polarized HT-29
      cells. Maximal production of IL-8 in response to Act required the presence of
      intracellular calcium, since chelation of calcium with BAPTA-AM significantly
      reduced Act-induced IL-8 production in HT-29 cells. We also examined activation
      of mitogen-activated protein kinases and, as demonstrated by Western blot
      analysis of apical side-treated polarized HT-29 cells, Act induced
      phosphorylation of p38, c-Jun NH(2)-terminal kinase, and extracellular signal
      regulated kinase 1/2. In addition, KinetWorks proteomics screening of whole-cell
      lysates revealed Act-induced phosphorylation of cyclic AMP-response element
      binding protein (CREB), c-Jun, adducin, protein kinase C, and signal transducer
      and activator of transcription 3 (STAT3) and decreased phosphorylation of protein
      kinase Balpha, v-raf-1 murine leukemia viral oncogene homolog 1 (i.e., Raf1), and
      STAT1. We verified activation of CREB and activator protein 1 in polarized cells
      by gel shift assay. This is the first description of human intestinal epithelial
      cell transcriptional alterations, phosphorylation or activation of signaling
      molecules, cytokine production, and calcium mobilization in response to this
      toxin.

PMID- 15845466
TI  - Intranasal vaccination induces protective immunity against intranasal infection
      with virulent Francisella tularensis biovar A.
AB  - The inhalation of Francisella tularensis biovar A causes pneumonic tularemia
      associated with high morbidity and mortality rates in humans. Exposure to F.
      tularensis usually occurs by accident, but there is increasing awareness that F.
      tularensis may be deliberately released in an act of bioterrorism or war. The
      development of a vaccine against pneumonic tularemia has been limited by a lack
      of information regarding the mechanisms required to protect against this disease.
      Vaccine models for F. tularensis in inbred mice would facilitate investigations
      of the protective mechanisms and significantly enhance vaccine development.
      Intranasal vaccination with the attenuated live vaccine strain (LVS) of F.
      tularensis reproducibly protected BALB/c mice, but not C57BL/6 mice, against
      intranasal and subcutaneous challenges with a virulent clinical isolate of F.
      tularensis biovar A (NMFTA1). The resistance of LVS-vaccinated BALB/c mice to
      intranasal NMFTA1 challenge was increased 100-fold by boosting with live NMFTA1
      but not with LVS. The protective response was specific for F. tularensis and
      required both CD4 and CD8 T cells. The vaccinated mice appeared outwardly healthy
      for more than 2 months after NMFTA1 challenge, even though NMFTA1 was recovered
      from more than half of the vaccinated mice. These results show that intranasal
      vaccination induces immunity that protects BALB/c mice from intranasal infection
      by F. tularensis biovar A.

PMID- 15845467
TI  - Molecular mechanism for connective tissue destruction by dipeptidyl
      aminopeptidase IV produced by the periodontal pathogen Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is a pathogen associated with adult periodontitis. It
      produces dipeptidyl aminopeptidase IV (DPPIV), which may act as a virulence
      factor by contributing to the degradation of connective tissue. We investigated
      the molecular mechanism by which DPPIV contributes to the destruction of
      connective tissue. DPPIV itself did not show gelatinase or collagenase activity
      toward human type I collagen, but it promoted the activity of the host-derived
      matrix metalloproteinase 2 (MMP-2) (gelatinase) and MMP-1 (collagenase). DPPIV
      bound to fibronectin and mediated the adhesion of P. gingivalis to fibronectin.
      Mutant DPPIV with catalytic Ser mutagenized to Ala (DPPSA) did not accelerate the
      degradation of collagen and gelatin by MMPs but retained fibronectin-binding
      activity. The adhesion of human gingival fibroblasts and NIH 3T3 cells to
      fibronectin was inhibited by DPPIV. Strain 4351ADPPSA exhibited an intermediate
      level of virulence in mice, between that of the strain expressing wild-type DPPIV
      (4351ADPP) and that of the strain harboring only the plasmid vector (4351AVEC).
      It is suggested that both activity promoting the degradation of collagen and
      gelatin and binding to fibronectin are required for full virulence. These results
      reveal novel biological functions of DPPIV and suggest a pathological role in the
      progression of periodontitis.

PMID- 15845468
TI  - Use of in vivo-induced antigen technology for identification of Escherichia coli
      O157:H7 proteins expressed during human infection.
AB  - Using in vivo-induced antigen technology (IVIAT), a modified immunoscreening
      technique that circumvents the need for animal models, we directly identified
      immunogenic Escherichia coli O157:H7 (O157) proteins expressed either
      specifically during human infection but not during growth under standard
      laboratory conditions or at significantly higher levels in vivo than in vitro.
      IVIAT identified 223 O157 proteins expressed during human infection, several of
      which were unique to this study. These in vivo-induced (ivi) proteins, encoded by
      ivi genes, mapped to the backbone, O islands (OIs), and pO157. Lack of in vitro
      expression of O157-specific ivi proteins was confirmed by proteomic analysis of a
      mid-exponential-phase culture of E. coli O157 grown in LB broth. Because ivi
      proteins are expressed in response to specific cues during infection and might
      help pathogens adapt to and counter hostile in vivo environments, those
      identified in this study are potential targets for drug and vaccine development.
      Also, such proteins may be exploited as markers of O157 infection in stool
      specimens.

PMID- 15845469
TI  - PavA of Streptococcus pneumoniae modulates adherence, invasion, and meningeal
      inflammation.
AB  - Pneumococcal adherence and virulence factor A (PavA) is displayed to the cell
      outer surface of Streptococcus pneumoniae and mediates pneumococcal binding to
      immobilized fibronectin. PavA, which lacks a typical gram-positive signal
      sequence and cell surface anchorage motif, is essential for pneumococcal
      virulence in a mouse infection model of septicemia. In this report the impact of
      PavA on pneumococcal adhesion to and invasion of eukaryotic cells and on
      experimental pneumococcal meningitis was investigated. In the experimental mouse
      meningitis model, the virulence of the pavA knockout mutant of S. pneumoniae D39,
      which did not show alterations of subcellular structures as indicated by electron
      microscopic studies, was strongly decreased. Pneumococcal strains deficient in
      PavA showed substantially reduced adherence to and internalization of epithelial
      cell lines A549 and HEp-2. Similar results were obtained with human brain-derived
      microvascular endothelial cells and human umbilical vein-derived endothelial
      cells. Attachment and internalization of pneumococci were not significantly
      affected by preincubation or cocultivations of pneumococci with anti-PavA
      antisera. Pneumococcal adherence was also not significantly affected by the
      addition of PavA protein. Complementation of the pavA knockout strain with
      exogenously added PavA polypeptide did not restore adherence of the mutant. These
      data suggest that PavA affects pneumococcal colonization by modulating expression
      or function of important virulence determinants of S. pneumoniae.

PMID- 15845470
TI  - Trypanosomes expressing a mosaic variant surface glycoprotein coat escape early
      detection by the immune system.
AB  - Host resistance to African trypanosomiasis is partially dependent on an early and
      strong T-independent B-cell response against the variant surface glycoprotein
      (VSG) coat expressed by trypanosomes. The repetitive array of surface epitopes
      displayed by a monotypic surface coat, in which identical VSG molecules are
      closely packed together in a uniform architectural display, cross-links cognate B
      cell receptors and initiates T-independent B-cell activation events. However,
      this repetitive array of identical VSG epitopes is altered during the process of
      antigenic variation, when former and nascent VSG proteins are transiently
      expressed together in a mosaic surface coat. Thus, T-independent B-cell
      recognition of the trypanosome surface coat may be disrupted by the introduction
      of heterologous VSG molecules into the coat structure. To address this
      hypothesis, we transformed Trypanosoma brucei rhodesiense LouTat 1 with the 117
      VSG gene from Trypanosoma brucei brucei MiTat 1.4 in order to produce VSG double
      expressers; coexpression of the exogenous 117 gene along with the endogenous
      LouTat 1 VSG gene resulted in the display of a mosaic VSG coat. Results presented
      here demonstrate that the host's ability to produce VSG-specific antibodies and
      activate B cells during early infection with VSG double expressers is compromised
      relative to that during infection with the parental strain, which displays a
      monotypic coat. These findings suggest a previously unrecognized mechanism of
      immune response evasion in which coat-switching trypanosomes fail to directly
      activate B cells until coat VSG homogeneity is achieved. This process affords an
      immunological advantage to trypanosomes during the process of antigenic
      variation.

PMID- 15845471
TI  - Pertussis toxin and adenylate cyclase toxin provide a one-two punch for
      establishment of Bordetella pertussis infection of the respiratory tract.
AB  - Previously we found that pertussis toxin (PT), an exotoxin virulence factor
      produced by Bordetella pertussis, plays an important early role in colonization
      of the respiratory tract by this pathogen, using a mouse intranasal infection
      model. In this study, we examined the early role played by another exotoxin
      produced by this pathogen, adenylate cyclase toxin (ACT). By comparing a wild
      type strain to a mutant strain (DeltaCYA) with an in-frame deletion of the cyaA
      gene encoding ACT, we found that the lack of ACT confers a significant peak (day
      7) colonization defect (1 to 2 log(10)). In mixed-infection experiments, the
      DeltaCYA strain was significantly outcompeted by the wild-type strain, and
      intranasal administration of purified ACT did not increase colonization by
      DeltaCYA. These data suggest that ACT benefits the bacterial cells that produce
      it and, unlike PT, does not act as a soluble factor benefiting the entire
      infecting bacterial population. Comparison of lower respiratory tract infections
      over the first 4 days after inoculation revealed that the colonization defect of
      the PT deletion strain was apparent earlier than that of DeltaCYA, suggesting
      that PT plays an earlier role than ACT in the establishment of B. pertussis
      infection. Examination of cells in the bronchoalveolar lavage fluid of infected
      mice revealed that, unlike PT, ACT does not appear to inhibit neutrophil influx
      to the respiratory tract early after infection but may combat neutrophil activity
      once influx has occurred.

PMID- 15845472
TI  - Acanthamoeba castellanii induces host cell death via a phosphatidylinositol 3
      kinase-dependent mechanism.
AB  - Granulomatous amoebic encephalitis due to Acanthamoeba castellanii is a serious
      human infection with fatal consequences, but it is not clear how the circulating
      amoebae interact with the blood-brain barrier and transmigrate into the central
      nervous system. We studied the effects of an Acanthamoeba encephalitis isolate
      belonging to the T1 genotype on human brain microvascular endothelial cells,
      which constitute the blood-brain barrier. Using an apoptosis-specific enzyme
      linked immunosorbent assay, we showed that Acanthamoeba induces programmed cell
      death in brain microvascular endothelial cells. Next, we observed that
      Acanthamoeba specifically activates phosphatidylinositol 3-kinase. Acanthamoeba
      mediated brain endothelial cell death was abolished using LY294002, a
      phosphatidylinositol 3-kinase inhibitor. These results were further confirmed
      using brain microvascular endothelial cells expressing dominant negative forms of
      phosphatidylinositol 3-kinase. This is the first demonstration that Acanthamoeba
      mediated brain microvascular endothelial cell death is dependent on
      phosphatidylinositol 3-kinase.

PMID- 15845473
TI  - Legionella pneumophila evades gamma interferon-mediated growth suppression
      through interleukin-10 induction in bone marrow-derived macrophages.
AB  - We examined the roles of Th1-Th2 cytokine cross talk in Legionella pneumophila
      infected bone marrow-derived (BM) macrophages in the presence of costimulation
      with interleukin-12 (IL-12) and IL-18. Treatment with gamma interferon (IFN
      gamma) alone or treatment with IL-12 in combination with IL-18 resulted in a 3-
      or 2-log reduction in bacterial numbers, respectively, in BM macrophages, whereas
      treatment with IL-12 or IL-18 alone had no effect. Significant amounts of IFN
      gamma were detected in the culture supernatants of infected macrophages
      stimulated with IL-12 and IL-18 in combination but not independently.
      Neutralization of IFN-gamma by antibody completely abolished the growth
      inhibitory effects of IL-12 and IL-18. Interestingly, higher infectivity ratios
      of L. pneumophila or the addition of increasing concentrations of heat-killed
      bacteria (HKB) suppressed the production of IFN-gamma, which resulted in the
      increased intracellular growth of bacteria. Significant amounts of IL-10 were
      detected in culture supernatants when Legionella-infected macrophages were
      cocultured with HKB. Furthermore, neutralization of IL-10 by antibody resulted in
      an increase in IFN-gamma production by infected BM macrophages when cocultured
      with HKB. Treatment of HKB with trypsin but not polymyxin B attenuated the growth
      promoting effects of HKB, suggesting the involvement of a protein component(s) in
      regulation of the growth of L. pneumophila. These findings demonstrate a crucial
      role of Th1-Th2 cross talk in L. pneumophila-infected BM macrophages. Our results
      also suggest that L. pneumophila modulates the cytokine balance from IFN-gamma
      driven Th1 to more Th2 responses, likely through the induction of IL-10 by a
      bacterial protein component(s). These data provide new insights not only into the
      cellular mechanisms of Th1-Th2 cross talk in Legionella-infected macrophages but
      also into the pathogenesis of L. pneumophila pneumonia in humans.

PMID- 15845474
TI  - Differential binding of Escherichia coli enterotoxins LT-IIa and LT-IIb and of
      cholera toxin elicits differences in apoptosis, proliferation, and activation of
      lymphoid cells.
AB  - Cholera toxin (CT), LT-IIa, and LT-IIb are potent adjuvants which induce distinct
      T-helper (Th)-cell cytokine profiles and immunoglobulin G (IgG) subclass and IgA
      antibody responses. To determine if the distinct immune regulatory effects
      observed for LT-IIa, LT-IIb, and CT are elicited by binding of the enterotoxins
      to their cognate ganglioside receptors, the lineages of lymphoid cells that
      interact with the three enterotoxins and their effects on various lymphocyte
      responses in vitro were evaluated. Binding patterns of LT-IIa, LT-IIb, and CT to
      several lymphoid cell populations were distinctive for each enterotoxin. LT-IIa
      and CT, but not LT-IIb, induced apoptosis in CD8(+) T cells. LT-IIa(T34I), a
      mutant with no detectable binding to gangliosides, did not induce apoptosis.
      Blockade of GM(1) on the surface of CD8(+) T cells by LT-IIa(T14I), a mutant that
      binds only to GM(1) but does not induce apoptosis, did not inhibit induction of
      apoptosis by LT-IIa. Mitogen-induced proliferation of CD8(+) T cells was
      abrogated by treatment with CT, while resting CD8(+) T cells which were sensitive
      to LT-IIa-induced apoptosis became more resistant to apoptosis after mitogen
      activation. Exposure to CT, but not to LT-IIa or LT-IIb, inhibited mitogen-driven
      CD4(+) T-cell proliferation and expression of CD25 and CD69. In mitogen
      stimulated B cells, CT, but not LT-IIa or LT-IIb, enhanced expression levels of
      CD86, while only CT induced B-cell differentiation into plasma cells. Thus, LT
      IIa, LT-IIb, and CT exhibit distinguishable immunomodulatory properties which are
      likely dependent upon their capacities to recognize different ganglioside
      receptors on lymphocytes.

PMID- 15845475
TI  - Outer membrane protein P6 of nontypeable Haemophilus influenzae is a potent and
      selective inducer of human macrophage proinflammatory cytokines.
AB  - Interactions of nontypeable Haemophilus influenzae (NTHI) with human macrophages
      contribute to the pathogenesis of NTHI-induced infection in humans. However, the
      immunologic mechanisms that initiate and perpetuate NTHI-mediated macrophage
      responses have not been well explored. Outer membrane protein (OMP) P6 is a
      conserved lipoprotein expressed by NTHI in vivo that possesses a Pam(3)Cys
      terminal motif, characteristic of immunoactive bacterial lipoproteins associated
      with Toll-like receptor signaling. We theorized that OMP P6 is a potent
      immunomodulator of human macrophages. To test this hypothesis, we purified OMP P6
      as well as OMP P2, the predominant NTHI outer membrane protein, and
      lipooligosaccharide (LOS), the specific endotoxin of NTHI, from NTHI strain 1479.
      Human blood monocyte-derived macrophages, purified from healthy donors, were
      incubated with each outer membrane constituent, and cytokine production of
      macrophage supernatants interleukin-1beta (IL-1beta), tumor necrosis factor alpha
      (TNF-alpha), IL-10, IL-12, and IL-8 was measured. OMP P6 selectively upregulated
      IL-10, TNF-alpha, and IL-8. While OMP P6 (0.1 mug/ml for 8 h) elicited slightly
      greater concentrations of IL-10, it resulted in over ninefold greater
      concentrations of TNF-alpha and over fourfold greater concentrations of IL-8 than
      did OMP P2. OMP P6 at doses as low as 10 pg/ml was still effective at induction
      of macrophage IL-8, while OMP P2 and LOS were not. OMP P6 of NTHI is a specific
      trigger of bacteria-induced human macrophage inflammatory events, with IL-8 and
      TNF-alpha as key effectors of P6-induced macrophage responses.

PMID- 15845476
TI  - Helicobacter pylori binds to CD74 on gastric epithelial cells and stimulates
      interleukin-8 production.
AB  - The pathogenesis associated with Helicobacter pylori infection requires
      consistent contact with the gastric epithelium. Although several cell surface
      receptors have been suggested to play a role in adhesion, the bacterium-host
      interactions that elicit host responses are not well defined. This study
      investigated the interaction of H. pylori with the class II major
      histocompatibility complex (MHC)-associated invariant chain (Ii; CD74), which was
      found to be highly expressed by gastric epithelial cells. Bacterial binding was
      increased when CD74 surface expression was increased by gamma interferon (IFN
      gamma) treatment or by fibroblast cells transfected with CD74, while binding was
      decreased by CD74 blocking antibodies, enzyme cleavage of CD74, and CD74-coated
      bacteria. H. pylori was also shown to bind directly to affinity-purified CD74 in
      the absence of class II MHC. Cross-linking of CD74 and the engagement of CD74
      were verified to stimulate IL-8 production by unrelated cell lines expressing
      CD74 in the absence of class II MHC. Increased CD74 expression by cells increased
      IL-8 production in response to H. pylori, and agents that block CD74 decreased
      these responses. The binding of H. pylori to CD74 presents a novel insight into
      an initial interaction of H. pylori with the gastric epithelium that leads to
      upregulation of inflammatory responses.

PMID- 15845477
TI  - Identification of an Immunomodulating Agent from Mycobacterium leprae.
AB  - A search for an immunomodulating agent from mycobacteria was carried out using
      Mycobacterium leprae. The antigenicity of each fraction of the bacterial
      membrane, which contains the most antigenic components of M. leprae, was assessed
      by using sera from paucibacillary leprosy. N-terminal sequencing of the serum
      reactive protein and functional assessment of the membrane fractions using
      monocyte-derived dendritic cells (DCs) identified major membrane protein II (MMP
      II) as one of the efficient T-cell-activating candidates. Purified MMP-II
      stimulated DCs from healthy individuals to produce interleukin-12 p70 and up
      regulated the surface expression of major histocompatibility complex class I and
      II, CD86, and CD83 molecules. Also, there was an increase in the percentage of
      CD83(+) cells in the DC population. Furthermore, MMP-II-pulsed DCs expressed
      their derivatives on their surfaces. Using Toll-like receptor 2 (TLR-2)-dependent
      receptor constructs, we found that TLR-2 signaling was involved in DC maturation
      induced by MMP-II. Taken together, MMP-II can be recognized as an
      immunomodulating protein in terms of activation of antigen-presenting cells and
      innate immunity.

PMID- 15845478
TI  - Role of interleukin-6 in mortality from and physiologic response to sepsis.
AB  - Previous studies have suggested that interleukin-6 (IL-6) serves as both a marker
      and a mediator for the severity of sepsis. We tested whether interleukin 6
      knockout (IL-6KO) mice were more susceptible to sepsis mortality induced by cecal
      ligation and puncture. IL-6KO and wild-type (WT) mice were subjected to
      increasing degrees of sepsis severity. Physiologic support was given with fluids
      and appropriate antibiotics. Plasma IL-6 levels were determined 6 h after the
      onset of sepsis, and a complete hematologic profile was performed on day 2. As
      expected, increasing sepsis severity resulted in greater and more rapid
      mortality. However, the mortality was nearly identical in the IL-6KO and WT mice.
      All WT septic mice had high plasma levels of IL-6 6 h after the onset of sepsis,
      while IL-6KO were near or below the lower limit of detection. Among the WT mice,
      mortality was significantly higher in mice with plasma IL-6 >3,000 pg/ml. Both IL
      6KO and WT mice destined to die in the early stages of sepsis had substantial and
      nearly identical weight gain in the first 24 h. However, at later stages the WT
      mice had significantly greater weight loss than the KO mice. The KO mice failed
      to develop the characteristic hypothermia within the first 24 h of severe sepsis
      routinely observed in the WT mice. These data demonstrate that IL-6 serves as a
      marker of disease severity in sepsis and does modulate some physiologic
      responses, but complete lack of IL-6 does not does not alter mortality due to
      sepsis.

PMID- 15845479
TI  - Candida albicans-secreted aspartic proteinases modify the epithelial cytokine
      response in an in vitro model of vaginal candidiasis.
AB  - Secreted aspartyl proteinases (Saps) are important virulence factors of Candida
      albicans during mucosal and disseminated infections and may also contribute to
      the induction of an inflammatory host immune response. We used a model of vaginal
      candidiasis based on reconstituted human vaginal epithelium (RHVE) to study the
      epithelial cytokine response induced by C. albicans. In order to study the impact
      of the overall proteolytic activity and of distinct Sap isoenzymes, we studied
      the effect of the proteinase inhibitor pepstatin A on the immune response and
      compared the cytokine expression pattern induced by the wild-type strain SC5314
      with the pattern induced by Sap-deficient mutants. Infection of RHVE with the C.
      albicans wild-type strain induced strong interleukin 1alpha (IL-1alpha), IL
      1beta, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, gamma
      interferon, and tumor necrosis factor alpha responses in comparison with cytokine
      expression in noninfected tissue. Addition of the aspartyl proteinase inhibitor
      pepstatin A strongly reduced the cytokine response of RHVE. Furthermore, SAP-null
      mutants lacking either SAP1 or SAP2 caused reduced tissue damage and had a
      significantly reduced potential to stimulate cytokine expression. In contrast,
      the vaginopathic and cytokine-inducing potential of mutants lacking SAP4 to SAP6
      was similar to that of the wild-type strain. These data show that the potential
      of specific Saps to cause tissue damage correlates with an epithelium-induced
      proinflammatory cytokine response, which may be crucial in controlling and
      managing C. albicans infections at the vaginal mucosa in vivo.

PMID- 15845480
TI  - Pneumocystis carinii activates the NF-kappaB signaling pathway in alveolar
      epithelial cells.
AB  - Pneumocystis carinii pneumonia (PcP) is a clinically important infection of
      immunocompromised patients. Although the interaction of Pneumocystis with the
      alveolar epithelium has been well documented, very little information regarding
      the epithelial response to Pneumocystis is currently available. In order to study
      Pneumocystis-epithelium interactions, a murine cell line derived specifically
      from an alveolar epithelial cell (AEC) was utilized. The coculture of murine AECs
      with mouse Pneumocystis induced a dose- and time-dependent release of the CXC
      chemokine MIP-2. Importantly, the specific removal of Pneumocystis from the
      preparation, or the pretreatment of AECs with sulfasalazine, a potent and
      specific inhibitor of NF-kappaB, nearly completely abrogated the chemokine
      response to Pneumocystis. Since the murine MIP-2 promoter contains consensus
      kappaB binding sequences, the ability of Pneumocystis to stimulate NF-kappaB
      signaling in AECs was examined. Pneumocystis stimulation of an AEC line stably
      transfected with a kappaB-dependent reporter construct triggered the NF-kappaB
      signaling pathway and reporter production. These data were confirmed in gel shift
      assays, providing direct evidence that Pneumocystis induced the nuclear
      translocation of the p50/p65 heterodimeric form of NF-kappaB. Maximal NF-kappaB
      activation was dependent upon direct contact with viable Pneumocystis organisms.
      These data demonstrate that Pneumocystis activates NF-kappaB signaling in AECs
      and establish a reporter cell line for studying NF-kappaB activation in AECs.
      Given the global regulatory functions of the NF-kappaB family, these findings
      suggest that Pneumocystis directly alters AEC gene expression in a manner that
      promotes pulmonary immune and inflammatory responses.

PMID- 15845481
TI  - Induction of nitric oxide synthase in Anopheles stephensi by Plasmodium
      falciparum: mechanism of signaling and the role of parasite
      glycosylphosphatidylinositols.
AB  - Malaria parasite (Plasmodium spp.) infection in the mosquito Anopheles stephensi
      induces significant expression of A. stephensi nitric oxide synthase (AsNOS) in
      the midgut epithelium as early as 6 h postinfection and intermittently
      thereafter. This induction results in the synthesis of inflammatory levels of
      nitric oxide (NO) in the blood-filled midgut that adversely impact parasite
      development. In mammals, P. falciparum glycosylphosphatidylinositols (PfGPIs) can
      induce NOS expression in immune and endothelial cells and are sufficient to
      reproduce the major effects of parasite infection. These effects are mediated in
      part by mimicry of insulin signaling by PfGPIs. In this study, we demonstrate
      that PfGPIs can induce AsNOS expression in A. stephensi cells in vitro and in the
      midgut epithelium in vivo. Signaling by P. falciparum merozoites and PfGPIs is
      mediated through A. stephensi Akt/protein kinase B and a pathway involving DSOR1,
      a mitogen-activated protein kinase kinase, and an extracellular signal-regulated
      kinase. However, despite the involvement of kinases that are also associated with
      insulin signaling in A. stephensi cells, signaling by P. falciparum and by PfGPIs
      is distinctively different from signaling by insulin. Therefore, although mimicry
      of insulin by PfGPIs appears to be restricted to mammalian hosts of P.
      falciparum, the conservation of PfGPIs as a prominent parasite-derived signal of
      innate immunity can now be extended to include Anopheles mosquitoes, indicating
      that parasite signaling of innate immunity is conserved in mosquito and mammalian
      cells.

PMID- 15845482
TI  - Synthesis and characterization of lipooligosaccharide-based conjugate vaccines
      for serotype B Moraxella catarrhalis.
AB  - Moraxella catarrhalis is an important cause of otitis media in children and
      respiratory tract infections in the elderly. Lipooligosaccharide (LOS) is a major
      surface antigen of the bacterium that elicits bactericidal antibodies.
      Serological studies show that three major LOS types (A, B, and C) have been
      identified among clinical isolates. Our previous studies demonstrated that the
      type A LOS-based conjugates were immunogenic in animals. In this study, LOS from
      type B strain 26397 was detoxified and conjugated to tetanus toxoid (TT) or a
      cross-reactive mutant (CRM) of diphtheria toxin to form detoxified LOS (dLOS)-TT
      and dLOS-CRM, respectively, as vaccine candidates. The molar ratios of dLOS to TT
      and CRM in the conjugates were 43:1 and 19:1, respectively, while both weight
      ratios were around 0.9. The antigenicity of the conjugates was similar to that of
      the LOS, as determined by enzyme-linked immunosorbent assay using a rabbit
      antiserum to strain 26397. Subcutaneous immunization with each conjugate elicited
      a 180- to 230-fold rise of serum anti-LOS immunoglobulin G in mice and >2,000
      fold rise in rabbits. In addition, both mouse and rabbit antisera showed elevated
      complement-mediated bactericidal activity against the homologous strain, and a
      representative rabbit antiserum showed bactericidal activity against nine of
      twelve clinical isolates studied. The bactericidal activity of the rabbit
      antiserum can be fully inhibited by the type B LOS but not the A or C LOS. These
      results indicate that the type B LOS-based conjugates can be used as vaccine
      components for further investigation.

PMID- 15845483
TI  - Immunological and protective effects of diepitopic subunit dental caries
      vaccines.
AB  - As a prelude to development of broader-spectrum vaccines for dental caries, we
      explored the immune potential of constructs combining epitopes from mutans
      streptococcal glucosyltransferases (GTF) and glucan binding protein B (GbpB). Two
      diepitopic peptide constructs were synthesized in a multiple antigenic peptide
      (MAP) format. Both constructs contained SYI, a 20-mer GbpB peptide that included
      a sequence having major histocompatibility complex class II binding
      characteristics. One diepitopic construct (SYI-CAT) also contained a 22-mer
      sequence from the catalytic domain of GTF. Another diepitopic construct (SYI-GLU)
      contained a 22-mer sequence from the glucan binding domain of GTF. To assess the
      ability of each construct to induce antibody reactive with GbpB and GTF native
      proteins, rats were injected subcutaneously with SYI-CAT, SYI-GLU, or the
      constituent monoepitopic constructs. Only the SYI-CAT construct induced
      significant levels of serum immunoglobulin G (IgG) and IgA antibody to both
      pathogenesis-associated proteins. Also, immunization with SYI-CAT significantly
      (P < 0.001) enhanced the antibody response to the CAT peptide. Experiments then
      compared experimental dental caries after immunization with SYI-CAT, SYI, or CAT
      MAP constructs, followed by infection with Streptococcus mutans strain SJr.
      Dental caries were lower in each peptide-immunized group than in the sham
      injected group. The level of protection after SYI-CAT immunization was similar to
      that after immunization with constituent MAP constructs. In another experiment,
      rats were infected with Streptococcus sobrinus strain 6715 under an identical
      protocol. Significant protection was observed on buccal surfaces in both SYI-CAT
      and CAT construct-immunized, but not in the SYI construct-immunized, groups.
      Thus, addition of the GbpB-derived SYI peptide to the GTF-derived CAT peptide
      construct not only enhanced the immunological response to CAT and GTF epitopes,
      but also extended the protective effect of the construct to include both S.
      mutans and S. sobrinus.

PMID- 15845484
TI  - Genomic subtraction followed by dot blot screening of Streptococcus pneumoniae
      clinical and carriage isolates identifies genetic differences associated with
      strains that cause otitis media.
AB  - Streptococcus pneumoniae strains are the leading cause of bacterial otitis media,
      yet little is known about specific bacterial factors important for this disease.
      We utilized a molecular epidemiological approach involving genomic subtraction of
      the S. pneumoniae serogroup 19 middle ear strain 5093 against the laboratory
      strain R6. Resulting subtraction PCR (sPCR) products were used to screen a panel
      of 93 middle ear, 90 blood, 35 carriage, and 58 cerebrospinal fluid isolates from
      young children to identify genes found more frequently among middle ear isolates.
      Probe P41, similar to a hypothetical protein of Brucella melitensis, occurred
      among 41% of middle ear isolates and was found 2.8 (95% confidence interval [CI],
      1.32 to 6.5), 3.3 (95% CI, 1.9 to 5.7), and 1.8 (95% CI, 1.1 to 3.0) times more
      frequently among middle ear strains than carriage, blood, or meningitis strains,
      respectively. sPCR fragment H10, similar to an unknown Streptococcus agalactiae
      protein, was present in 31% of middle ear isolates and occurred 3.6 (95% CI, 1.2
      to 11.2), 2.8 (95% CI, 1.5 to 5.4), and 2.6 (95% CI, 1.2 to 5.5) times more often
      among middle ear isolates than carriage, blood, or meningitis strains,
      respectively. These studies have identified two genes of potential importance in
      otitis media virulence. Further studies are warranted to outline the precise role
      of these genes in otitis media pathogenesis.

PMID- 15845485
TI  - The surface protein Pls of methicillin-resistant Staphylococcus aureus is a
      virulence factor in septic arthritis.
AB  - Pls, a surface protein of certain methicillin-resistant Staphylococcus aureus
      strains, is associated with poor bacterial adherence to solid-phase fibronectin
      and immunoglobulin G, as well as with reduced invasion of cultured epithelial
      cells. Here the importance of Pls for the development of septic arthritis and
      sepsis was investigated by using a mouse model. Mice inoculated with a pls
      knockout mutant developed a much milder arthritis and showed less grave weight
      reduction than mice infected with the wild-type Pls(+) clinical isolate. Also,
      the pls mutant induced a significantly lower frequency of mortality than the wild
      type strain. The bacterial load of the kidneys was larger in mice infected with
      the Pls(+) strain than in animals challenged with the pls mutant. However, there
      was no evident inflammatory effect due to the Pls molecule alone, as indicated by
      knee injection of purified Pls. In conclusion, the results show that Pls is a
      virulence factor for septic arthritis and sepsis.

PMID- 15845486
TI  - Identification of genes required for avian Escherichia coli septicemia by
      signature-tagged mutagenesis.
AB  - Infections with avian pathogenic Escherichia coli (APEC) cause colibacillosis, an
      acute and largely systemic disease resulting in significant economic losses in
      poultry industry worldwide. Although various virulence-associated genes have been
      identified in APEC, their actual role in pathogenesis is still not fully
      understood, and, furthermore, certain steps of the infection process have not
      been related to previously identified factors. Here we describe the application
      of a signature-tagged transposon mutagenesis (STM) approach to identify critical
      genes required for APEC infections in vivo. Twenty pools of about 1,800 IMT5155
      (O2:H5) mutants were screened in an infection model using 5-week-old chickens,
      and potentially attenuated mutants were subjected to a secondary screen and in
      vivo competition assays to confirm their attenuation. A total of 28 genes
      required for E. coli septicemia in chickens were identified as candidates for
      further characterization. Among these disrupted genes, six encode proteins
      involved in biosynthesis of extracellular polysaccharides and
      lipopolysaccharides; two encode iron transporters that have not been previously
      characterized in APEC in in vivo studies, and four showed similarity to membrane
      or periplasmic proteins. In addition, several metabolic enzymes, putative
      proteins with unknown function, and open reading frames with no similarity to
      other database entries were identified. This genome-wide analysis has identified
      both novel and previously known factors potentially involved in pathogenesis of
      APEC infection.

PMID- 15845487
TI  - Identification and characterization of human surfactant protein A binding protein
      of Mycoplasma pneumoniae.
AB  - Mycoplasma pneumoniae infections represent a major primary cause of human
      respiratory diseases, exacerbate other respiratory disorders, and are associated
      with extrapulmonary pathologies. Cytadherence is a critical step in mycoplasma
      colonization, aided by a network of mycoplasma adhesins and cytadherence
      accessory proteins which mediate binding to host cell receptors. Furthermore, the
      respiratory mucosa is enriched with extracellular matrix components, including
      surfactant proteins, fibronectin, and mucin, which provide additional in vivo
      targets for mycoplasma parasitism. In this study we describe interactions between
      M. pneumoniae and human surfactant protein-A (hSP-A). Initially, we found that
      viable M. pneumoniae cells bound to immobilized hSP-A in a dose- and calcium
      (Ca(2+))-dependent manner. Mild trypsin treatment of intact mycoplasmas reduced
      binding markedly (80 to 90%) implicating a surface-associated mycoplasma
      protein(s). Using hSP-A-coupled Sepharose affinity chromatography and
      polyacrylamide gel electrophoresis, we identified a 65-kDa hSP-A binding protein
      of M. pneumoniae. The presence of Ca(2+) enhanced binding of the 65-kDa protein
      to hSP-A, which was reduced by the divalent cation-chelating agent, EDTA. The 65
      kDa hSP-A binding protein of M. pneumoniae was identified by sequence analysis as
      a novel protein (MPN372) possessing a putative S1-like subunit of pertussis toxin
      at the amino terminus (amino acids 1 to 226), with the remaining amino acids (227
      to 591) exhibiting no homology with other subunits of pertussis toxin, other
      known toxins, or any reported proteins. Recombinant MPN372 (MPN372) bound to hSP
      A in a dose-dependent manner, which was markedly reduced by preincubation with
      mouse recombinant MPN372 antisera. Also, adherence of viable M. pneumoniae cells
      to hSP-A was inhibited by recombinant MPN372 antisera, demonstrating that MPN372,
      a previously designated hypothetical protein, is surface exposed and mediates
      mycoplasma attachment to hSP-A.

PMID- 15845488
TI  - Characterization of Salmonella-induced cell death in human macrophage-like THP-1
      cells.
AB  - Salmonella strains are facultative intracellular pathogens that produce marked
      cytopathology during infection of host cells. Different forms of cytopathic
      effects have been associated with the virulence systems encoded by the two
      Salmonella pathogenicity islands (SPI-1 and SPI-2) and the spv locus. We used
      Salmonella enterica serovar Dublin to investigate the induction of cytopathology
      during infection of the human macrophage-like cell line THP-1. Analysis of host
      cells by flow cytometry using a fluorescent terminal deoxynucleotidyltransferase
      dUTP-biotin nick end labeling (TUNEL) assay revealed that 70% of THP-1 cells
      showed DNA fragmentation after 4 h of infection, increasing to greater than 90%
      by 5.5 h. Moreover, the results showed that gentamicin-killed or chloramphenicol
      treated bacteria did not induce DNA fragmentation. Serovar Dublin strains with
      mutations in SPI-1, SPI-2, or spvB induced these cytopathic effects similar to
      wild-type bacteria. In contrast, a mutation in the phoP regulatory gene abolished
      DNA fragmentation in the TUNEL assay. Caspase-3 activation was detected during
      Salmonella infection of THP-1 cells, but caspase-8 and caspase-9 activities were
      not found. However, inhibition of caspase-3 did not block Salmonella-induced DNA
      fragmentation. These results identify a previously undetected apoptotic effect in
      Salmonella-infected cells that is dependent on phoP gene function.

PMID- 15845489
TI  - Rapid acquisition of isolate-specific antibodies to chondroitin sulfate A
      adherent plasmodium falciparum isolates in Ghanaian primigravidae.
AB  - Recent evidence suggests that pregnancy-associated malaria (PAM), associated with
      maternal anemia and low birth weight, results from preferential sequestration of
      parasitized red blood cells (pRBC) in the placenta via binding of variant surface
      antigens (VSA) expressed on the surface of pRBC to chondroitin sulfate A (CSA).
      The VSA mediating CSA binding (VSA(CSA)) and thus sequestration of pRBC in the
      placenta are antigenically distinct from those that mediate pRBC sequestration
      elsewhere in the body, and it has been suggested that VSA(CSA) are relatively
      conserved and may thus constitute an attractive target for vaccination against
      PAM. Using flow cytometry, levels of antibody to VSA and VSA(CSA) expressed on
      the surface of red blood cells infected with Plasmodium falciparum isolates were
      measured during pregnancy and lactation in Ghanaian primigravid women enrolled in
      a trial of maternal vitamin A supplementation. Antibody responses to VSA(CSA)
      were detected within the first trimester of pregnancy and increased with
      increasing duration of pregnancy, and they seemed to be isolate specific,
      indicating that different CSA-adherent parasite lines express antigenically
      distinct VSA and thus may not be as antigenically conserved as has been
      previously suggested. Levels of anti-VSA(CSA) were not significantly associated
      with placental malarial infection determined by histology, indicating that
      primary immune responses to VSA(CSA) may not be sufficient to eradicate placental
      parasitemia in primigravidae.

PMID- 15845490
TI  - Cross-reactive surface epitopes on chondroitin sulfate A-adherent Plasmodium
      falciparum-infected erythrocytes are associated with transcription of var2csa.
AB  - Malaria in pregnancy is associated with placental accumulation of Plasmodium
      falciparum-infected erythrocytes (IE) that adhere to chondroitin sulfate A (CSA).
      Adhesion is mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1), a
      variant parasite protein expressed on the surface of IE and encoded by var genes.
      Rabbit antiserum was generated against the CSA-adherent P. falciparum line CS2,
      in which the dominant var transcribed is var2csa, a relatively conserved var gene
      that has been associated with CSA adhesion. Anti-CS2 recognized genetically
      distinct CSA-adherent P. falciparum lines but not CD36-adherent parent lines.
      Reactivity with anti-CS2 correlated with the level of adhesion to CSA.
      Fluorescence-activated cell sorting according to binding of anti-CS2 showed
      reactivity was associated with CSA adhesion and transcription of var2csa. These
      data are consistent with the hypothesis that var2csa encodes a PfEMP1 expressed
      on the surface of IE, which mediates adhesion to CSA and is relatively conserved
      between genetically distinct strains of P. falciparum.

PMID- 15845491
TI  - Gamma irradiation or CD4+-T-cell depletion causes reactivation of latent
      Salmonella enterica serovar Typhimurium infection in C3H/HeN mice.
AB  - Upon infection with Salmonella, a host develops an immune response to limit
      bacterial growth and kill and eliminate the pathogen. Salmonella has evolved
      mechanisms to remain dormant within the body, only to reappear (reactivate) at a
      later time when the immune system is abated. We have developed an in vivo model
      for studying reactivation of Salmonella enterica serovar Typhimurium infection in
      mice. Upon subcutaneous infection, C3H/HeN (Ity(r)) mice showed an increase in
      bacterial numbers in livers and spleens, which reached a peak on day 19. After
      full recovery from the infection, these mice were irradiated or depleted of
      CD4(+) T cells. The mice displayed a secondary infection peak in livers and
      spleens with a course similar to that of the primary infection. We concluded that
      CD4(+) T cells are involved in active suppression of S. enterica serovar
      Typhimurium during latency. The role of CD4(+) T cells during primary infection
      with S. enterica serovar Typhimurium is well established. This is the first study
      to describe a role of CD4(+) T cells during the latent phase of S. enterica
      serovar Typhimurium infection.

PMID- 15845492
TI  - Boosting of DNA vaccine-elicited gamma interferon responses in humans by exposure
      to malaria parasites.
AB  - A mixture of DNA plasmids expressing five Plasmodium falciparum pre-erythrocyte
      stage antigens was administered with or without a DNA plasmid encoding human
      granulocyte-macrophage colony-stimulating factor (hGM-CSF) as an immune enhancer.
      After DNA immunization, antigen-specific gamma interferon (IFN-gamma) responses
      were detected by ELISPOT in 15/31 volunteers to multiple class I- and/or class II
      restricted T-cell epitopes derived from all five antigens. Responses to multiple
      epitopes (</=7) were detected simultaneously in some volunteers. By 4 weeks after
      challenge with P. falciparum parasites, 23/31 volunteers had positive IFN-gamma
      responses and the magnitude of responses was increased from 2- to 143-fold.
      Nonetheless, none was protected against malaria. Volunteers who received hGM-CSF
      had a reduced frequency of IFN-gamma responses to class I peptides compared to
      those who only received plasmids expressing P. falciparum proteins before
      challenge (3/23 versus 3/8; P = 0.15) or after parasite challenge (4/23 versus
      5/8; P = 0.015) but not to class II peptides before or after challenge. The
      responses to one antigen (P. falciparum circumsporozoite protein [PfCSP]) were
      similar among volunteers who received the five-gene mixture compared to
      volunteers who only received the PfCSP DNA plasmid in a previous study. In
      summary, DNA-primed IFN-gamma responses were boosted in humans by exposure to
      native antigen on parasites, coadministration of a plasmid expressing hGM-CSF had
      a negative effect on boosting of class I-restricted IFN-gamma responses, and
      there was no evidence that immunization with PfCSP DNA in the mixture reduced T
      cell responses to PfCSP compared to when it was administered alone.

PMID- 15845493
TI  - The Brucella abortus Cu,Zn superoxide dismutase is required for optimal
      resistance to oxidative killing by murine macrophages and wild-type virulence in
      experimentally infected mice.
AB  - Two-dimensional gel electrophoretic analysis of cell lysates from Brucella
      abortus 2308 and the isogenic hfq mutant Hfq3 revealed that the RNA binding
      protein Hfq (also known as host factor I or HF-I) is required for the optimal
      stationary phase production of the periplasmic Cu,Zn superoxide dismutase SodC.
      An isogenic sodC mutant, designated MEK2, was constructed from B. abortus 2308 by
      gene replacement, and the sodC mutant exhibited much greater susceptibility to
      killing by O(2)(-) generated by pyrogallol and the xanthine oxidase reaction than
      the parental 2308 strain supporting a role for SodC in protecting this bacterium
      from O(2)(-) of exogenous origin. The B. abortus sodC mutant was also found to be
      much more sensitive to killing by cultured resident peritoneal macrophages from
      C57BL6J mice than 2308, and the attenuation displayed by MEK2 in cultured murine
      macrophages was enhanced when these phagocytes were treated with gamma interferon
      (IFN-gamma). The attenuation displayed by the B. abortus sodC mutant in both
      resting and IFN-gamma-activated macrophages was alleviated, however, when these
      host cells were treated with the NADPH oxidase inhibitor apocynin. Consistent
      with its increased susceptibility to killing by cultured murine macrophages, the
      B. abortus sodC mutant also displayed significant attenuation in experimentally
      infected C57BL6J mice compared to the parental strain. These experimental
      findings indicate that SodC protects B. abortus 2308 from the respiratory burst
      of host macrophages. They also suggest that reduced SodC levels may contribute to
      the attenuation displayed by the B. abortus hfq mutant Hfq3 in the mouse model.

PMID- 15845494
TI  - Effects of oligopeptide permease in group a streptococcal infection.
AB  - The oligopeptide permease (Opp) of group A streptococci (GAS) is a membrane
      associated protein and belongs to the ATP-binding cassette transporter family. It
      is encoded by a polycistronic operon containing oppA, oppB, oppC, oppD, and oppF.
      The biological function of these genes in GAS is poorly understood. In order to
      understand more about the effects of Opp on GAS virulence factors, an oppA
      isogenic mutant was constructed by using an integrative plasmid to disrupt the
      opp operon and confirmed by Southern blot hybridization. No transcript was
      detected in the oppA isogenic mutant by Northern blot analysis and reverse
      transcriptase PCR. The growth curve for the oppA isogenic mutant was similar to
      that for wild-type strain A-20. The oppA isogenic mutant not only decreased the
      transcription of speB, speX, and rofA but also increased the transcription of
      speF, sagA (streptolysin S-associated gene A), slo (streptolysin O), pel
      (pleotrophic effect locus), and dppA (dipeptide permease). No effects on the
      transcription of emm, sda, speJ, speG, rgg, and csrR were found. The phenotypes
      of the oppA mutant were restored by the oppA revertant and by the complementation
      strain. The oppA mutant caused less mortality and tissue damage than the wild
      type strain when inoculated into BALB/c mice via an air pouch. Based on these
      data, we suggest that the opp operon plays an important role in the pathogenesis
      of GAS infection.

PMID- 15845495
TI  - Binding properties and adhesion-mediating regions of the major sheath protein of
      Treponema denticola ATCC 35405.
AB  - There is growing evidence that a number of oral Treponema species, in particular
      Treponema denticola, are associated with the progression of human periodontal
      disease. The major sheath (or surface) protein (Msp) of T. denticola is
      implicated in adhesion of bacteria to host cells and tissue proteins and is
      likely to be an important virulence factor. However, the binding regions of the
      Msp are not known. We have purified from Escherichia coli recombinant Msp (rMsp)
      polypeptides corresponding to the following: full-length Msp (rMsp) minus 13 N
      terminal amino acid (aa) residues, an amino-terminal fragment (rN-Msp, 189 aa
      residues), a 57-aa residue segment from the central region (rV-Msp), and a C
      terminal fragment (rC-Msp, 272 aa residues). rMsp (530 aa residues) bound to
      immobilized fibronectin, keratin, laminin, collagen type I, fibrinogen,
      hyaluronic acid, and heparin. The N- and V-region polypeptides, but not rC-Msp,
      also bound to these substrates. Binding of rMsp to fibronectin was targeted to
      the N-terminal heparin I/fibrin I domain. Antibodies to the N-region or V-region
      polypeptides, but not antibodies to the rC-Msp fragment, blocked adhesion of T.
      denticola ATCC 35405 cells to a range of host protein molecules. These results
      suggest that the N-terminal half of Msp carries epitopes that are surface exposed
      and that are involved in mediating adhesion. Binding of rMsp onto the cell
      surface of low-level fibronectin-binding Treponema isolates conferred a 10-fold
      increase in fibronectin binding. This confirms that Msp functions autonomously as
      an adhesin and raises the possibility that phenotypic complementation of
      virulence functions might occur within mixed populations of Treponema species.

PMID- 15845496
TI  - Characterization of the major secreted zinc metalloprotease- dependent
      glycerophospholipid:cholesterol acyltransferase, PlaC, of Legionella pneumophila.
AB  - Legionella pneumophila, an intracellular pathogen causing a severe pneumonia,
      possesses distinct lipolytic activities which have not been completely assigned
      to specific enzymes so far. We cloned and characterized a gene, plaC, encoding a
      protein with high homology to PlaA, the major secreted lysophospholipase A of L.
      pneumophila and to other hydrolytic enzymes belonging to the GDSL family. Here we
      show that L. pneumophila plaC mutants possessed reduced phospholipase A and
      lysophospholipase A activities and lacked glycerophospholipid:cholesterol
      acyltransferase activity in their culture supernatants. The mutants' reduced
      phospholipase A and acyltransferase activities were complemented by
      reintroduction of an intact copy of plaC. Additionally, plaC conferred increased
      lysophospholipase A and glycerophospholipid:cholesterol acytransferase activities
      to recombinant Escherichia coli. Furthermore, PlaC was shown to be another
      candidate exported by the L. pneumophila type II secretion system and was
      activated by a factor present in the bacterial culture supernatant dependent on
      the zinc metalloprotease. Finally, the role of plaC in intracellular infection of
      Acanthamoeba castellanii and U937 macrophages with L. pneumophila was assessed,
      and plaC was found to be dispensable. Thus, L. pneumophila possesses another
      secreted lipolytic enzyme, a protein with acyltransferase, phospholipase A, and
      lysophospholipase A activities. This enzyme is distinguished from the previously
      characterized phospholipases A and lysophospholipases A by its capacity not only
      to cleave fatty acids from lipids but to transfer them to cholesterol.
      Cholesterol is an important compound of eukaryotic membranes, and an
      acyltransferase might be a tool for host cell modification to fit the needs of
      the bacterium.

PMID- 15845497
TI  - Induction of Mycobacterium tuberculosis-specific primary and secondary T-cell
      responses in interleukin-15-deficient mice.
AB  - Several studies have provided evidence that interleukin-15 (IL-15) can enhance
      protective immune responses against Mycobacterium tuberculosis infection.
      However, the effects of IL-15 deficiency on the functionality of M. tuberculosis
      specific CD4 and CD8 T cells are unknown. In this study, we investigated the
      generation and maintenance of effector and memory T-cell responses following M.
      tuberculosis infection of IL-15(-/-) mice. IL-15(-/-) mice had slightly higher
      bacterial numbers during chronic infection, which were accompanied by an increase
      in gamma interferon (IFN-gamma)-producing CD4 and CD8 T cells. There was no
      evidence of increased apoptosis or a defect in proliferation of CD8 effector T
      cells following M. tuberculosis infection. The induction of cytotoxic and IFN
      gamma CD8 T-cell responses was normal in the absence of IL-15 signaling. The
      infiltration of CD4 and CD8 T cells into the lungs of "immune" IL-15(-/-) mice
      was delayed in response to M. tuberculosis challenge. These findings demonstrate
      that efficient effector CD4 and CD8 T cells can be developed following M.
      tuberculosis infection in the absence of IL-15 but that recall T-cell responses
      may be impaired.

PMID- 15845498
TI  - Escherichia coli K1 RS218 interacts with human brain microvascular endothelial
      cells via type 1 fimbria bacteria in the fimbriated state.
AB  - Escherichia coli K1 is a major gram-negative organism causing neonatal
      meningitis. E. coli K1 binding to and invasion of human brain microvascular
      endothelial cells (HBMEC) are a prerequisite for E. coli penetration into the
      central nervous system in vivo. In the present study, we showed using DNA
      microarray analysis that E. coli K1 associated with HBMEC expressed significantly
      higher levels of the fim genes compared to nonassociated bacteria. We also showed
      that E. coli K1 binding to and invasion of HBMEC were significantly decreased
      with its fimH deletion mutant and type 1 fimbria locked-off mutant, while they
      were significantly increased with its type 1 fimbria locked-on mutant. E. coli K1
      strains associated with HBMEC were predominantly type 1 fimbria phase-on (i.e.,
      fimbriated) bacteria. Taken together, we showed for the first time that type 1
      fimbriae play an important role in E. coli K1 binding to and invasion of HBMEC
      and that type 1 fimbria phase-on E. coli is the major population interacting with
      HBMEC.

PMID- 15845499
TI  - Serologic responses to ACYW135 polysaccharide meningococcal vaccine in Saudi
      children under 5 years of age.
AB  - An immunization campaign with meningococcal ACYW135 polysaccharide vaccine was
      conducted in 2003 by the Saudi Arabian Ministry of Health and included a study to
      evaluate the immune responses in children under 5 years of age in the Al Qassim
      region of Saudi Arabia. Children who were >/=24 months old were given one dose of
      tetravalent polysaccharide vaccine, while younger children were given two doses
      with an interval of 2 to 3 months. Blood samples were collected prevaccination
      and 1 month after the second dose for children younger than 24 months old and 1
      month after the single dose for older children. Serogroup-specific antibody
      responses were determined by serum bactericidal antibody (SBA) assays and a
      tetraplex immunoglobulin G (IgG) bead assay. Significant increases in the
      proportions of individuals who were >/=24 months old with SBA titers of >/=8 were
      observed pre- to postvaccination for all serogroups. Age-dependent increases in
      the percentage of individuals with SBA titers of >/=8 1 month postvaccination
      were observed for each serogroup. Age-dependent increases in postvaccination IgG
      levels were observed for serogroup A (menA), serogroup W135 (menW), and serogroup
      Y (menY) but not for serogroup C (menC). Two doses of tetravalent polysaccharide
      vaccine in individuals who were </=18 months old were poorly immunogenic for
      menC, menW, and menY. However, for menA, 42% of the children who were 18 months
      old were putatively protected with SBA titers of >/=8. A high percentage of
      subjects who were >/=2 years of age were putatively protected for menA; a similar
      level was observed for menY for children who were 4 years of age but not for
      younger children. However, for menC and menW poor levels of putative protection
      were still evident at 4 years of age.

PMID- 15845500
TI  - Differential induction of the toll-like receptor 4-MyD88-dependent and 
      independent signaling pathways by endotoxins.
AB  - The biological response to endotoxin mediated through the Toll-like receptor 4
      (TLR4)-MD-2 receptor complex is directly related to lipid A structure or
      configuration. Endotoxin structure may also influence activation of the MyD88
      dependent and -independent signaling pathways of TLR4. To address this
      possibility, human macrophage-like cell lines (THP-1, U937, and MM6) or murine
      macrophage RAW 264.7 cells were stimulated with picomolar concentrations of
      highly purified endotoxins. Harvested supernatants from previously stimulated
      cells were also used to stimulate RAW 264.7 or 23ScCr (TLR4-deficient)
      macrophages (i.e., indirect induction). Neisseria meningitidis
      lipooligosaccharide (LOS) was a potent direct inducer of the MyD88-dependent
      pathway molecules tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL
      1beta), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory
      protein 3alpha (MIP-3alpha), and the MyD88-independent molecules beta interferon
      (IFN-beta), nitric oxide, and IFN-gamma-inducible protein 10 (IP-10). Escherichia
      coli 55:B5 and Vibrio cholerae lipopolysaccharides (LPSs) at the same pmole/ml
      lipid A concentrations induced comparable levels of TNF-alpha, IL-1beta, and MIP
      3alpha, but significantly less IFN-beta, nitric oxide, and IP-10. In contrast,
      LPS from Salmonella enterica serovars Minnesota and Typhimurium induced amounts
      of IFN-beta, nitric oxide, and IP-10 similar to meningococcal LOS but much less
      TNF-alpha and MIP-3alpha in time course and dose-response experiments. No MyD88
      dependent or -independent response to endotoxin was seen in TLR4-deficient cell
      lines (C3H/HeJ and 23ScCr) and response was restored in TLR4-MD-2-transfected
      human embryonic kidney 293 cells. Blocking the MyD88-dependent pathway by DNMyD88
      resulted in significant reduction of TNF-alpha release but did not influence
      nitric oxide release. IFN-beta polyclonal antibody and IFN-alpha/beta receptor 1
      antibody significantly reduced nitric oxide release. N. meningitidis endotoxin
      was a potent agonist of both the MyD88-dependent and -independent signaling
      pathways of the TLR4 receptor complex of human macrophages. E. coli 55:B5 and
      Vibrio cholerae LPS, at the same picomolar lipid A concentrations, selectively
      induced the MyD88-dependent pathway, while Salmonella LPS activated the MyD88
      independent pathway.

PMID- 15845501
TI  - Human Lyme arthritis and the immunoglobulin G antibody response to the 37
      kilodalton arthritis-related protein of Borrelia burgdorferi.
AB  - In Borrelia burgdorferi-infected C3H-scid mice, antiserum to a differentially
      expressed, 37-kDa spirochetal outer-surface protein, termed arthritis-related
      protein (Arp), has been shown to prevent or reduce the severity of arthritis. In
      this study, we determined the immunoglobulin G (IgG) antibody responses to this
      spirochetal protein in single serum samples from 124 antibiotic-treated human
      patients with early or late manifestations of Lyme disease and in serial serum
      samples from 20 historic, untreated patients who were followed longitudinally
      from early infection through the period of arthritis. These 20 patients were
      representative of the spectrum of the severity and duration of Lyme arthritis.
      Among the 124 antibiotic-treated patients, 53% with culture-proven erythema
      migrans (EM) had IgG responses to recombinant glutathione S-transferase (GST)
      Arp, as did 59% of the patients with facial palsy and 68% of those with Lyme
      arthritis. In addition, 75 to 80% of the 20 past, untreated patients had
      reactivity with this protein when EM was present, during initial episodes of
      joint pain, or during the maximal period of arthritis. There was no association
      at any of these three time points between GST-Arp antibody levels and the
      severity of the maximal attack of arthritis or the total duration of arthritis.
      Thus, after the first several weeks of infection, 60 to 80% of patients had IgG
      antibody responses to GST-Arp, but this response did not correlate with the
      severity or duration of Lyme arthritis.

PMID- 15845502
TI  - Pseudomonas aeruginosa SoxR does not conform to the archetypal paradigm for SoxR
      dependent regulation of the bacterial oxidative stress adaptive response.
AB  - SoxR is a transcriptional regulator that controls an oxidative stress response in
      Escherichia coli. The regulator is primarily activated by superoxide anion
      dependent oxidation. Activated SoxR turns on transcription of a single gene,
      soxS, which encodes a transcriptional regulator that activates a regulon that
      includes dozens of oxidative stress response genes. SoxR homologues have been
      identified in many bacterial species, including the opportunistic pathogen
      Pseudomonas aeruginosa. However, the expected SoxR partner, SoxS, has not been
      found in P. aeruginosa. Thus, the primary gene target(s) of P. aeruginosa SoxR is
      unknown and the involvement of this regulator in the oxidative stress response of
      the bacterium remains unclear. We utilized transcriptome profiling to identify
      the P. aeruginosa SoxR regulon and constructed and characterized an unmarked P.
      aeruginosa DeltasoxR mutant. We provide evidence indicating that P. aeruginosa
      SoxR activates a six-gene regulon in response to O(2)(.-)-induced stress. The
      regulon includes three transcriptional units: (i) the recently identified mexGHI
      ompD four-gene operon, which encodes a multidrug efflux pump system involved in
      quorum-sensing signal homeostasis; (ii) gene PA3718, encoding a probable efflux
      pump; and (iii) gene PA2274, encoding a probable monooxygenase. We also
      demonstrate that P. aeruginosa SoxR is not a key regulatory player in the
      oxidative stress response. Finally, we show that P. aeruginosa SoxR is required
      for virulence in a mouse model of intrapulmonary infection. These results
      demonstrate that the E. coli-based SoxRS paradigm does not hold in P. aeruginosa
      and foster new hypotheses for the possible physiological role of P. aeruginosa
      SoxR.

PMID- 15845503
TI  - Induction of Nod1 and Nod2 intracellular pattern recognition receptors in murine
      osteoblasts following bacterial challenge.
AB  - Osteoblasts produce an array of immune molecules following bacterial challenge
      that could recruit leukocytes to sites of infection and promote inflammation
      during bone diseases, such as osteomyelitis. Recent studies from our laboratory
      have shed light on the mechanisms by which this cell type can perceive and
      respond to bacteria by demonstrating the functional expression of members of the
      Toll-like family of cell surface pattern recognition receptors by osteoblasts.
      However, we have shown that bacterial components fail to elicit immune responses
      comparable with those seen following challenge with the intracellular pathogens
      salmonellae and Staphylococcus aureus. In the present study, we show that UV
      killed bacteria and invasion-defective bacterial strains elicit significantly
      less inflammatory cytokine production than their viable wild-type counterparts.
      Importantly, we demonstrate that murine osteoblasts express the novel
      intracellular pattern recognition receptors Nod1 and Nod2. Levels of mRNA
      encoding Nod molecules and protein expression are significantly and
      differentially increased from low basal levels following exposure to these
      disparate bacterial pathogens. In addition, we have shown that osteoblasts
      express Rip2 kinase, a critical downstream effector molecule for Nod signaling.
      Furthermore, to begin to establish the functional nature of Nod expression, we
      show that a specific ligand for Nod proteins can significantly augment immune
      molecule production by osteoblasts exposed to either UV-inactivated bacteria or
      bacterial lipopolysaccharide. As such, the presence of Nod proteins in
      osteoblasts could represent an important mechanism by which this cell type
      responds to intracellular bacterial pathogens of bone.

PMID- 15845504
TI  - Induction of strain-transcending immunity against Plasmodium chabaudi adami
      malaria with a multiepitope DNA vaccine.
AB  - A major goal of current malaria vaccine programs is to develop multivalent
      vaccines that will protect humans against the many heterologous malaria strains
      that circulate in endemic areas. We describe a multiepitope DNA vaccine, derived
      from a genomic Plasmodium chabaudi adami DS DNA expression library of 30,000
      plasmids, which induces strain-transcending immunity in mice against challenge
      with P. c. adami DK. Segregation of this library and DNA sequence analysis
      identified vaccine subpools encoding open reading frames (ORFs)/peptides of >9
      amino acids [aa] (the V9+ pool, 303 plasmids) and >50 aa (V50+ pool, 56
      plasmids), respectively. The V9+ and V50+ plasmid vaccine subpools significantly
      cross-protected mice against heterologous P. c. adami DK challenge, and
      protection correlated with the induction of both specific gamma interferon
      production by splenic cells and opsonizing antibodies. Bioinformatic analysis
      showed that 22 of the V50+ ORFs were polypeptides conserved among three or more
      Plasmodium spp., 13 of which are predicted hypothetical proteins. Twenty-nine of
      these ORFs are orthologues of predicted Plasmodium falciparum sequences known to
      be expressed in the blood stage, suggesting that this vaccine pool encodes
      multiple blood-stage antigens. The results have implications for malaria vaccine
      design by providing proof-of-principle that significant strain-transcending
      immunity can be induced using multiepitope blood-stage DNA vaccines and suggest
      that both cellular responses and opsonizing antibodies are necessary for optimal
      protection against P. c. adami.

PMID- 15845505
TI  - Infection of the reproductive tract and eggs with Salmonella enterica serovar
      pullorum in the chicken is associated with suppression of cellular immunity at
      sexual maturity.
AB  - Salmonella enterica serovar Pullorum causes persistent infections in laying hens.
      Splenic macrophages are the main site of persistence. At sexual maturity, numbers
      of bacteria increase and spread to the reproductive tract, which may result in
      vertical transmission to eggs or chicks. In this study we demonstrate that both
      male and female chickens may develop a carrier state following infection but that
      the increases in bacterial numbers and spread to the reproductive tract are
      phenomena restricted to hens, indicating that such changes are likely to be
      related to the onset of egg laying. The immunological responses during the
      carrier state and through the onset of laying in hens were determined. These
      indicate that chickens produce both humoral and T-cell responses to infection,
      but at the onset of laying both the T-cell response to Salmonella and nonspecific
      responses to mitogenic stimulation fall sharply in both infected and noninfected
      birds. The fall in T-cell responsiveness coincided with the increase in numbers
      of Salmonella serovar Pullorum and its spread to the reproductive tract. Three
      weeks after the onset of egg laying, T-cell responsiveness began to increase and
      bacterial numbers declined. Specific antibody levels changed little at the onset
      of laying but increased following the rise in bacterial numbers in a manner
      reminiscent of a secondary antibody response to rechallenge. These findings
      indicate that a nonspecific suppression of cellular responses occurs at the onset
      of laying and plays a major role the ability of Salmonella serovar Pullorum to
      infect the reproductive tract, leading to transmission to eggs. The loss of T
      cell activity at the point of laying also has implications for Salmonella
      enterica serovar Enteritidis infection and transmission to eggs, along with its
      control by vaccination offering a "window of opportunity" in which infection may
      occur.

PMID- 15845506
TI  - Efficient Ex vivo stimulation of Mycobacterium tuberculosis-specific T cells by
      genetically detoxified Bordetella pertussis adenylate cyclase antigen toxoids.
AB  - Mycobacterium tuberculosis is a significant threat to global health.
      Mycobacterium bovis BCG vaccine provides only partial protection, and the skin
      test reagent used to aid diagnosis of both active and latent tuberculosis,
      purified protein derivative (PPD), lacks specificity and sensitivity. The use of
      genetically detoxified Bordetella pertussis adenylate cyclase toxin (CyaA) as a
      delivery system for two immunodominant proteins of M. tuberculosis that are of
      greater specificity than PPD, early-secreted antigenic target 6-kDa protein (ESAT
      6) and culture filtrate protein 10 (CFP-10), was therefore investigated. CyaA
      toxoids incorporating these antigens were able to restimulate T cells from more
      than 91% tuberculosis patients and healthy sensitized donors. Delivery of antigen
      by CyaA decreased by 10-fold the amount of ESAT-6 and CFP-10 required to
      restimulate T cells, and in low responders, the overall frequency of gamma
      interferon-producing cells detected by enzyme-linked immunospot assay was
      increased (P < 0.01 for both antigens). Delivery of ESAT-6 and CFP-10 by CyaA
      enabled the detection of both CD4(+) and CD8(+) T cells: these responses could be
      blocked by inhibition of major histocompatibility complex class II or class I,
      respectively. Covalent linkage of antigen to the CyaA vector was required for
      enhancement to occur, as a mixture of mock CyaA toxoid plus recombinant ESAT-6
      did not lead to enhancement. In a simplified whole-blood model to detect
      tuberculosis infection, the frequency of positive responses to CFP-10 was
      increased by CyaA delivery, a potentially important attribute that could
      facilitate the identification of latent infection.

PMID- 15845507
TI  - B-cell and T-cell immune responses to experimental Helicobacter pylori infection
      in humans.
AB  - The acute antibody and T-cell immune response to Helicobacter pylori infection in
      humans has not been studied systematically. Serum from H. pylori-naive volunteers
      challenged with H. pylori and cured after 4 or 12 weeks was tested by enzyme
      linked immunosorbent assays for anti-H. pylori-specific immunoglobulin M (IgM)
      and IgA established using bacterial lysates from homologous (the infecting
      strain) and heterologous H. pylori. Proteins recognized by IgM antibody were
      identified by mass spectrometry of immunoreactive bands separated by two
      dimensional gel electrophoresis. Mucosal T-cell subsets (CD4, CD8, CD3, and CD30
      cells) were assessed by immunohistochemistry. All 18 infected volunteers
      developed H. pylori-specific IgM responses to both homologous or heterologous H.
      pylori antigens. H. pylori antigens reacted with IgM antibody at 4 weeks
      postinfection. IgM Western blotting showed immunoreactivity of postinfection
      serum samples to multiple H. pylori proteins with molecular weights ranging
      between 9,000 (9K) to 150K with homologous strains but only a 70K band using
      heterologous antigens. Two-dimensional electrophoresis demonstrated that
      production of H. pylori-specific IgM antibodies was elicited by H. pylori
      flagellins A and B, urease B, ABC transporter binding protein, heat shock protein
      70 (DnaK), and alkyl hydroperoxide reductase. Mucosal CD3, CD4, and CD8 T-cell
      numbers increased following infection. IgM antibody responses were detected to a
      range of homologous H. pylori antigens 2 to 4 weeks postchallenge. The majority
      of H. pylori proteins were those involved in motility and colonization and may
      represent targets for vaccine development.

PMID- 15845508
TI  - Extracellular carbohydrate-containing polymers of a model biofilm-producing
      strain, Staphylococcus epidermidis RP62A.
AB  - Staphylococcus aureus and coagulase-negative staphylococci, primarily
      Staphylococcus epidermidis, are recognized as a major cause of nosocomial
      infections associated with the use of implanted medical devices. It has been
      established that clinical isolates often produce a biofilm, which is involved in
      adherence to biomaterials and provides enhanced resistance of bacteria against
      host defenses and antibiotic treatments. It has been thought that the
      staphylococcal biofilm contains two polysaccharides, one responsible for primary
      cell adherence to biomaterials (polysaccharide/adhesin [PS/A]) and an antigen
      that mediates bacterial aggregation (polysaccharide intercellular adhesin [PIA]).
      In the present paper we present an improved procedure for preparation of PIA that
      conserves its labile substituents and avoids contamination with by-products.
      Based on structural analysis of the polysaccharide antigens and a thorough
      overview of the previously published data, we concluded that PIA from S.
      epidermidis is structurally identical to the recently described poly-beta-(1-->6)
      N-acetylglucosamine from PS/A-overproducing strain S. aureus MN8m. We also show
      that another carbohydrate-containing polymer, extracellular teichoic acid (EC
      TA), is an essential component of S. epidermidis RP62A biofilms. We demonstrate
      that the relative amounts of extracellular PIA and EC TA produced depend on the
      growth conditions. Moderate shaking or static culture in tryptic soy broth favors
      PIA production, while more EC TA is produced in brain heart infusion medium.

PMID- 15845509
TI  - The vaccine candidate Vibrio cholerae 638 is protective against cholera in
      healthy volunteers.
AB  - Vibrio cholerae 638 is a living candidate cholera vaccine strain attenuated by
      deletion of the CTXPhi prophage from C7258 (O1, El Tor Ogawa) and by insertion of
      the Clostridium thermocellum endoglucanase A gene into the hemagglutinin/protease
      coding sequence. This vaccine candidate was previously found to be well tolerated
      and immunogenic in volunteers. This article reports a randomized, double-blind,
      placebo-controlled trial conducted to test short-term protection conferred by 638
      against subsequent V. cholerae infection and disease in volunteers in Cuba. A
      total of 45 subjects were enrolled and assigned to receive vaccine or placebo.
      The vaccine contained 10(9) CFU of freshly harvested 638 buffered with 1.3%
      NaHCO(3), while the placebo was buffer alone. After vaccine but not after placebo
      intake, 96% of volunteers had at least a fourfold increase in vibriocidal
      antibody titers, and 50% showed a doubling of at least the lipopolysaccharide
      specific immunoglobulin A titers in serum. At 1 month after vaccination, five
      volunteers from the vaccine group and five from the placebo group underwent an
      exploratory challenge study with 10(9) CFU of DeltaCTXPhi attenuated mutant
      strain V. cholerae 81. Only two volunteers from the vaccine group shed strain 81
      in their feces, but none of them experienced diarrhea; in the placebo group, all
      volunteers excreted the challenge strain, and three had reactogenic diarrhea. An
      additional 12 vaccinees and 9 placebo recipients underwent challenge with 7 x
      10(5) CFU of virulent strain V. cholerae 3008 freshly harvested from a brain
      heart infusion agar plate and buffered with 1.3% NaHCO(3). Three volunteers (25%)
      from the vaccine group and all from the placebo group shed the challenge agent in
      their feces. None of the 12 vaccinees but 7 volunteers from the placebo group had
      diarrhea, and 2 of the latter exhibited severe cholera (>5,000 g of diarrheal
      stool). These results indicate that at 1 month after ingestion of a single oral
      dose (10(9) CFU) of strain 638, volunteers remained protected against cholera
      infection and disease provoked by the wild-type challenge agent V. cholerae 3008.
      We recommend that additional vaccine lots of 638 be prepared under good
      manufacturing practices for further evaluation.

PMID- 15845510
TI  - Relapsing fever spirochetes contain chromosomal genes with unique direct tandemly
      repeated sequences.
AB  - Genome sequencing of the relapsing fever spirochetes Borrelia hermsii and
      Borrelia turicatae identified three open reading frames (ORFs) on the chromosomes
      that contained internal, tandemly repeated amino acid sequences that were absent
      in the Lyme disease spirochete Borrelia burgdorferi. The predicted amino acid
      sequences of these genes (BH0209, BH0512, and BH0553) have hydrophobic N termini,
      indicating that these proteins may be secreted. B. hermsii transcribed the three
      ORFs in vitro, and the BH0512- and BH0553-encoded proteins (PBH-512 and PBH-553)
      were produced in vitro and in experimentally infected mice. PBH-512 and PBH-553
      were on the spirochete's outer surface, and antiserum to these proteins reduced
      the adherence of B. hermsii to red blood cells. PCR analyses of 28 isolates of B.
      hermsii and 8 isolates of B. turicatae demonstrated polymorphism in each gene
      correlated with the number of repeats. Serum samples from relapsing fever
      patients reacted with recombinant PBH-512 and PBH-553, suggesting that these
      proteins are produced during human infection. These polymorphic proteins may be
      involved in the pathogenicity of these relapsing fever spirochetes and provide a
      mechanism for antigenic heterogeneity within their populations.

PMID- 15845511
TI  - Mutants of Mycobacterium tuberculosis lacking three of the five rpf-like genes
      are defective for growth in vivo and for resuscitation in vitro.
AB  - Mycobacterium tuberculosis contains five genes, rpfA through rpfE, that bear
      significant homology to the resuscitation-promoting factor (rpf) gene of
      Micrococcus luteus, whose product is required to resuscitate the growth of
      dormant cultures of M. luteus and is essential for the growth of this organism.
      Previous studies have shown that deletion of any one of the five rpf-like genes
      did not affect the growth or survival of M. tuberculosis in vitro. In conjunction
      with the results of whole-genome expression profiling, this finding was
      indicative of their functional redundancy. In this study, we demonstrate that the
      single deletion mutants are phenotypically similar to wild-type M. tuberculosis
      H37Rv in vivo. The deletion of individual rpf-like genes had no discernible
      effect on the growth or long-term survival of M. tuberculosis in liquid culture,
      and the ability to resuscitate spontaneously from a nonculturable state in a most
      probable number assay was also unaffected for the three strains tested (the
      DeltarpfB, DeltarpfD, and DeltarpfE strains). In contrast, two multiple strains,
      KDT8 (DeltarpfA-mutation DeltarpfC DeltarpfB) and KDT9 (DeltarpfA DeltarpfC
      DeltarpfD), which lack three of the five rpf-like genes, were significantly yet
      differentially attenuated in a mouse infection model. These mutants were also
      unable to resuscitate spontaneously in vitro, demonstrating the importance of the
      Rpf-like proteins of M. tuberculosis in resuscitation from the nonculturable
      state. These results strongly suggest that the biological functions of the five
      rpf-like genes of M. tuberculosis are not wholly redundant and underscore the
      potential utility of these proteins as targets for therapeutic intervention.

PMID- 15845512
TI  - Synthetic toll-like receptor 4 agonists stimulate innate resistance to infectious
      challenge.
AB  - A compound family of synthetic lipid A mimetics (termed the aminoalkyl
      glucosaminide phosphates [AGPs]) was evaluated in murine infectious disease
      models of protection against challenge with Listeria monocytogenes and influenza
      virus. For the Listeria model, intravenous administration of AGPs was followed by
      intravenous bacterial challenge 24 h later. Spleens were harvested 2 days
      postchallenge for the enumeration of CFU. For the influenza virus model, mice
      were challenged with virus via the intranasal/intrapulmonary route 48 h after
      intranasal/intrapulmonary administration of AGPs. The severity of disease was
      assessed daily for 3 weeks following challenge. Several types of AGPs provided
      strong protection against influenza virus or Listeria challenge in wild-type
      mice, but they were inactive in the C3H/HeJ mouse, demonstrating the dependence
      of the AGPs on toll-like receptor 4 (TLR4) signaling for the protective effect.
      Structure-activity relationship studies showed that the activation of innate
      immune effectors by AGPs depends primarily on the lengths of the secondary acyl
      chains within the three acyl-oxy-acyl residues and also on the nature of the
      functional group attached to the aglycon component. We conclude that the
      administration of synthetic TLR4 agonists provides rapid pharmacologic induction
      of innate resistance to infectious challenge by two different pathogen classes,
      that this effect is mediated via TLR4, and that structural differences between
      AGPs can have dramatic effects on agonist activity in vivo.

PMID- 15845513
TI  - Cytolethal distending toxin (CDT)-negative Campylobacter jejuni strains and anti
      CDT neutralizing antibodies are induced during human infection but not during
      colonization in chickens.
AB  - The cytolethal distending toxin (CDT) of Campylobacter jejuni was detectable,
      using an in vitro assay, in most but not all of 24 strains tested. The reason for
      the absence of toxin activity in these naturally occurring CDT-negative C. jejuni
      strains was then investigated at the genetic level. CDT is encoded by three
      highly conserved genes, cdtA, -B, and -C. In the CDT-negative strains, two types
      of mutation were identified. The CDT activities of C. jejuni strains possessing
      both types of mutation were successfully complemented with the functional genes
      of C. jejuni 11168. The first type of mutation comprised a 667-bp deletion across
      cdtA and cdtB and considerable degeneration in the remainder of the cdt locus.
      Using a PCR technique to screen for this deletion, this mutation occurred in
      fewer than 3% of 147 human, veterinary, and environmental strains tested. The
      second type of mutation involved at least four nonsynonymous nucleotide changes,
      but only the replacement of proline with serine at CdtB position 95 was
      considered important for CDT activity. This was confirmed by site-directed
      mutagenesis. This type of mutation also occurred in fewer than 3% of strains as
      determined using a LightCycler biprobe assay. The detection of two CDT-negative
      clinical isolates raised questions about the role of CDT in some cases of human
      campylobacteriosis. To determine if anti-CDT antibodies are produced in human
      infection, a toxin neutralization assay was developed and validated using rabbit
      antisera. Pooled human sera from infected patients neutralized the toxin,
      indicating expression and immunogenicity during infection. However, no
      neutralizing antibodies were detected in colonized chickens despite the
      expression of CDT in the avian gut as indicated by reverse transcription-PCR.

PMID- 15845514
TI  - Invasion of epithelial cells by locus of enterocyte effacement-negative
      enterohemorrhagic Escherichia coli.
AB  - The majority of enterohemorrhagic Escherichia coli (EHEC) strains associated with
      severe disease carry the locus of enterocyte effacement (LEE) pathogenicity
      island, which encodes the ability to induce attaching and effacing lesions on the
      host intestinal mucosa. While LEE is essential for colonization of the host in
      these pathogens, strains of EHEC that do not carry LEE are regularly isolated
      from patients with severe disease, although little is known about the way these
      organisms interact with the host epithelium. In this study, we compared the
      adherence properties of clinical isolates of LEE-negative EHEC with those of LEE
      positive EHEC O157:H7. Transmission electron microscopy revealed that LEE
      negative EHEC O113:H21 was internalized by Chinese hamster ovary (CHO-K1)
      epithelial cells and that intracellular bacteria were located within a membrane
      bound vacuole. In contrast, EHEC O157:H7 remained extracellular and intimately
      attached to the epithelial cell surface. Quantitative gentamicin protection
      assays confirmed that EHEC O113:H21 was invasive and also showed that several
      other serogroups of LEE-negative EHEC were internalized by CHO-K1 cells. Invasion
      by EHEC O113:H21 was significantly reduced in the presence of the cytoskeletal
      inhibitors cytochalasin D and colchicine and the pan-Rho GTPase inhibitor
      compactin, whereas the tyrosine kinase inhibitor genistein had no significant
      impact on bacterial invasion. In addition, we found that EHEC O113:H21 was
      invasive for the human colonic cell lines HCT-8 and Caco-2. Overall these studies
      suggest that isolates of LEE-negative EHEC may employ a mechanism of host cell
      invasion to colonize the intestinal mucosa.

PMID- 15845515
TI  - CD46-independent binding of neisserial type IV pili and the major pilus adhesin,
      PilC, to human epithelial cells.
AB  - Neisseria gonorrhoeae is a gram-negative bacterial pathogen which infects the
      human mucosal epithelium. An early critical event in neisserial infection is the
      type IV pilus-mediated adherence to the host cell. The PilC protein, located on
      the pilus tip, has earlier been identified as the major pilus adhesin. Previous
      studies suggested that the cell surface protein CD46 is a pilus receptor for
      Neisseria. We investigated the role of CD46 in pilus-mediated gonococcal
      infection of epithelial cells. Differences in binding efficiencies of piliated
      gonococci as well as purified pilus adhesin PilC2 on human epithelial cell lines
      did not correlate to the level of surface-expressed CD46. Additionally, no
      binding of piliated gonococci or PilC2 protein was observed on CD46-transfected
      CHO and MDCK cells. Furthermore, specific down-regulation of CD46 expression in
      human epithelial cell lines by RNA interference did not alter the binding
      efficiency of piliated gonococci or purified PilC2 protein, although other CD46
      dependent processes, such as measles virus infection and C3b cleavage, were
      significantly reduced. These data support the notion that pilus-mediated
      gonococcal infection of epithelial cells can occur in a CD46-independent manner,
      thus questioning the function of CD46 as an essential pilus receptor for
      pathogenic neisseriae.

PMID- 15845516
TI  - A monoclonal antibody that conveys in vitro killing and partial protection in
      experimental syphilis binds a phosphorylcholine surface epitope of Treponema
      pallidum.
AB  - Immunization with purified Treponema pallidum outer membrane vesicles (OMV) has
      previously resulted in high-titer complement-dependent serum bactericidal
      activity. In this study, OMV immunization resulted in the isolation of a
      monoclonal antibody, M131, with complement-dependent killing activity. Passive
      immunization of rabbits with M131 administered intravenously conferred
      significant immunity demonstrated by the failure of syphilitic lesions to appear
      at 29% of intradermal challenge sites (7/24) and a mean delay of approximately 8
      days to lesion appearance at the remaining sites (17/24). M131 not only bound to
      OMV and to the surfaces of intact motile T. pallidum cells but also bound to
      organisms whose outer membranes were removed, indicating both surface and
      subsurface locations for the killing target. This target was determined to be a
      T. pallidum lipid. Lipid extracted from T. pallidum and made into liposomes bound
      M131. Reverse-phase high-pressure liquid chromatography separation and fraction
      collection mass spectrometry (LC-MS+) of T. pallidum lipid showed that the target
      of M131 was phosphorylcholine. M131 binding required both liposome formation and
      a critical concentration of phospholipid containing phosphorylcholine, suggesting
      that the epitope has both a conformational and a compositional requirement. M131
      did not react with red blood cells, which have phosphorylcholine-containing
      lipids in their exterior membrane leaflets, or with Venereal Disease Research
      Laboratory antigen that also contains phosphorylcholine, further indicating the
      specificity of M131. This is the first physical demonstration of an antigen on
      the T. pallidum surface and indication that such a surface antigen can be a
      target of immunity.

PMID- 15845517
TI  - Structural and genetic diversity of group B streptococcus capsular
      polysaccharides.
AB  - Group B Streptococcus (GBS) is an important pathogen of neonates, pregnant women,
      and immunocompromised individuals. GBS isolates associated with human infection
      produce one of nine antigenically distinct capsular polysaccharides which are
      thought to play a key role in virulence. A comparison of GBS polysaccharide
      structures of all nine known GBS serotypes together with the predicted amino acid
      sequences of the proteins that direct their synthesis suggests that the evolution
      of serotype-specific capsular polysaccharides has proceeded through en bloc
      replacement of individual glycosyltransferase genes with DNA sequences that
      encode enzymes with new linkage specificities. We found striking heterogeneity in
      amino acid sequences of synthetic enzymes with very similar functions, an
      observation that supports horizontal gene transfer rather than stepwise
      mutagenesis as a mechanism for capsule variation. Eight of the nine serotypes
      appear to be closely related both structurally and genetically, whereas serotype
      VIII is more distantly related. This similarity in polysaccharide structure
      strongly suggests that the evolutionary pressure toward antigenic variation
      exerted by acquired immunity is counterbalanced by a survival advantage conferred
      by conserved structural motifs of the GBS polysaccharides.

PMID- 15845518
TI  - Small-molecule inhibitors specifically targeting type III secretion.
AB  - The type III secretion (TTS) system is used by several animal and plant pathogens
      to deliver effector proteins into the cytosol of the eukaryotic target cell as a
      strategy to evade the defense reactions elicited by the infected organism. The
      fact that these systems are highly homologous implies that novel antibacterial
      agents that chemically attenuate the pathogens via a specific interaction with
      the type III secretion mechanism can be identified. A number of small organic
      molecules having this potential have recently been identified (A. M. Kauppi, R.
      Nordfelth, H. Uvell, H. Wolf-Watz, and M. Elofsson, Chem. Biol. 10:241-249,
      2003). Using different reporter gene constructs, we showed that compounds that
      belong to a class of acylated hydrazones of different salicylaldehydes target the
      TTS system of Yersinia pseudotuberculosis. One of these compounds, compound 1,
      was studied in detail and was found to specifically block Yop effector secretion
      under in vitro conditions by targeting the TTS system. In this respect the drug
      mimics the well-known effect of calcium on Yop secretion. In addition, compound 1
      inhibits Yop effector translocation after infection of HeLa cells without
      affecting the eukaryotic cells or the bacteria. A HeLa cell model that mimics in
      vivo conditions showed that compound 1 chemically attenuates the pathogen to the
      advantage of the eukaryotic cell. Thus, our results show proof of concept, i.e.,
      that small compounds targeting the TTS system can be identified, and they point
      to the possible use of TTS inhibitors as a novel class of antibacterial agents.

PMID- 15845519
TI  - CD40 signaling in macrophages induces activity against an intracellular pathogen
      independently of gamma interferon and reactive nitrogen intermediates.
AB  - Gamma interferon (IFN-gamma) is the major inducer of classical activation of
      macrophages. Classically activated mouse macrophages acquire antimicrobial
      activity that is largely dependent on the production of reactive nitrogen
      intermediates. However, protection against important intracellular pathogens can
      take place in the absence of IFN-gamma and nitric oxide synthase 2 (NOS2). Using
      Toxoplasma gondii as a model, we investigated if CD40 signaling generates mouse
      macrophages with effector function against an intracellular pathogen despite the
      absence of priming with IFN-gamma and lack of production of reactive nitrogen
      intermediates. CD40-stimulated macrophages acquired anti-T. gondii activity that
      was not inhibited by a neutralizing anti-IFN-gamma monoclonal antibody but was
      ablated by the neutralization of tumor necrosis factor alpha (TNF-alpha).
      Moreover, while the induction of anti-T. gondii activity in response to CD40
      stimulation was unimpaired in macrophages from IFN-gamma(-/-) mice, macrophages
      from TNF receptor 1/2(-/-) mice failed to respond to CD40 engagement. In contrast
      to IFN-gamma-lipopolysaccharide, CD40 stimulation did not induce NOS2 expression
      and did not trigger production of reactive nitrogen intermediates. Neither N(G)
      monomethyl-l-arginine nor diphenyleneiodonium chloride affected the induction of
      anti-T. gondii activity in response to CD40. Finally, macrophages from NOS2(-/-)
      mice acquired anti-T. gondii activity in response to CD40 stimulation that was
      similar to that of macrophages from wild-type mice. These results demonstrate
      that CD40 induces the antimicrobial activity of macrophages against an
      intracellular pathogen despite the lack of two central features of classically
      activated macrophages: priming with IFN-gamma and production of reactive nitrogen
      intermediates.

PMID- 15845520
TI  - Laccase expression in murine pulmonary Cryptococcus neoformans infection.
AB  - Cryptococcus neoformans laccase expression during murine infection was
      investigated in lung tissue by immunohistochemistry and immunogold electron
      microscopy. Laccase was detected in the fungal cell cytoplasm, cell wall, and
      capsule in vivo. The amount of laccase found in different sites varied as a
      function of the time of infection.

PMID- 15845522
TI  - Surface analyses and immune reactivities of major cell wall-associated proteins
      of group a streptococcus.
AB  - A proteomic analysis was undertaken to identify cell wall-associated proteins of
      Streptococcus pyogenes. Seventy-four distinct cell wall-associated proteins were
      identified, 66 of which were novel. Thirty-three proteins were immunoreactive
      with pooled S. pyogenes-reactive human antisera. Biotinylation of the GAS cell
      surface identified 23 cell wall-associated proteins that are surface exposed.

PMID- 15845521
TI  - The Bartonella vinsonii subsp. arupensis immunodominant surface antigen BrpA
      gene, encoding a 382-kilodalton protein composed of repetitive sequences, is a
      member of a multigene family conserved among bartonella species.
AB  - Bartonella proteins that elicit an antibody response during an infection are
      poorly defined; therefore, to characterize antigens recognized by the host, a
      Bartonella genomic expression library was screened with serum from an infected
      mouse. This process led to the discovery of a Bartonella vinsonii subsp.
      arupensis gene encoding a 382-kDa protein, part of a gene family encoding large
      proteins, each containing multiple regions of repetitive segments. The genes were
      termed brpA to -C (bartonella repeat protein) and bore significant similarity to
      genes encoding the BadA adhesin protein and members of the variably expressed
      outer membrane protein family of proteins from Bartonella henselae and Bartonella
      quintana, respectively.

PMID- 15845523
TI  - A hypothetical protein of Streptococcus mutans is critical for biofilm formation.
AB  - Inactivation of the Smu0630 gene of Streptococcus mutans resulted in dramatic
      decreases in biofilm formation, regardless of the carbohydrate source. The
      Smu0630 protein contained numerous interesting features, including a possible
      signal sequence and two conserved regions of repeated sequences. Smu0630 may
      represent a potential target for novel therapeutics.

PMID- 15845524
TI  - Construction and characterization of Listeria monocytogenes mutants with in-frame
      deletions in the response regulator genes identified in the genome sequence.
AB  - Two-component systems are widely distributed in prokaryotes where they control
      gene expression in response to diverse stimuli. To study the role of the sixteen
      putative two-component systems of Listeria monocytogenes systematically, in frame
      deletions were introduced into 15 out of the 16 response regulator genes and the
      resulting mutants were characterized. With one exception the deletion of the
      individual response regulator genes has only minor effects on in vitro and in
      vivo growth of the bacteria. The mutant carrying a deletion in the ortholog of
      the Bacillus subtilis response regulator gene degU showed a clearly reduced
      virulence in mice, indicating that DegU is involved in the regulation of
      virulence-associated genes.

PMID- 15845525
TI  - Requirement of MgtC for Brucella suis intramacrophage growth: a potential
      mechanism shared by Salmonella enterica and Mycobacterium tuberculosis for
      adaptation to a low-Mg2+ environment.
AB  - A Brucella suis mgtC mutant is defective for growth within macrophages and in low
      Mg(2+) medium. These phenotypes are strikingly similar to those observed with
      mgtC mutants from Salmonella enterica and Mycobacterium tuberculosis, two other
      pathogens that proliferate within phagosomes. MgtC appears as a remarkable
      virulence factor that would have been acquired by distantly related intracellular
      pathogens to contribute to the adaptation to a low-Mg(2+) environment in the
      phagosome.

PMID- 15845526
TI  - Tumor necrosis factor alpha plays a role in the acceleration of atherosclerosis
      by Chlamydia pneumoniae in mice.
AB  - The role of tumor necrosis factor alpha (TNF-alpha) in Chlamydia pneumoniae
      atherogenesis was evaluated in TNF-alpha p55 receptor-deficient C57BL/6J mice fed
      a high-fat/high-cholesterol diet. No acceleration of atherosclerotic lesion
      development was observed in infected mice compared to uninfected mice, indicating
      that TNF-alpha plays a role in the acceleration of atherosclerosis by C.
      pneumoniae.

PMID- 15845527
TI  - Maturation of the Legionella pneumophila-containing phagosome into a
      phagolysosome within gamma interferon-activated macrophages.
AB  - Legionella pneumophila is an intracellular pathogen that modulates the biogenesis
      of its phagosome to evade endocytic vesicle traffic. The Legionella-containing
      phagosome (LCP) does not acquire any endocytic markers and is remodeled by the
      endoplasmic reticulum during early stages. Here we show that intracellular
      replication of L. pneumophila is inhibited in gamma interferon (IFN-gamma)
      activated, bone marrow-derived mouse macrophages and IFN-gamma-activated, human
      monocyte-derived macrophages in a dose-dependent manner. This inhibition of
      intracellular replication is associated with the maturation of the LCP into a
      phagolysosome, as documented by the acquisition of LAMP-2, cathepsin D, and
      lysosomal tracer Texas Red ovalbumin, and with the failure of the LCP to be
      remodeled by the rough endoplasmic reticulum. We conclude that IFN-gamma
      activated macrophages override the ability of L. pneumophila to evade endocytic
      fusion and that the LCP is processed through the "default" endosomal-lysosomal
      degradation pathway.

PMID- 15845528
TI  - Interleukin-15 enhances innate and adaptive immune responses to blood-stage
      malaria infection in mice.
AB  - Compared to C57BL/6 wild-type mice, interleukin-15(-/-) (IL-15(-/-)) mice showed
      delayed clearance of Plasmodium chabaudi AS infection, lower type 1 cytokine
      production, impaired dendritic cell and NK cell functions, and lower titers of
      malaria-specific antibodies. Thus, IL-15 supports early control and timely
      resolution of blood-stage malaria through promotion of Th1-dependent innate and
      adaptive immune responses.

PMID- 15845529
TI  - Regulation of the mitogen-activated protein kinases by Brucella spp. expressing a
      smooth and rough phenotype: relationship to pathogen invasiveness.
AB  - By comparing smooth wild-type Brucella spp. to their rough mutants, we show that
      the LPS O chain restricted the activation of the ERK1/2 and p38 mitogen-activated
      protein kinase (MAPK) pathways, thus preventing the synthesis of immune mediators
      that regulate host defense. We conclude that the MAPKs are a target for immune
      intervention by virulent smooth Brucella.

PMID- 15845530
TI  - The concentration of apolipoprotein A-I decreases during experimentally induced
      acute-phase processes in pigs.
AB  - In this work, apolipoprotein A-I (ApoA-I) was purified from pig sera. The
      responses of this protein after sterile inflammation and in animals infected with
      Actinobacillus pleuropneumoniae or Streptococcus suis were investigated.
      Decreases in the concentrations of ApoA-I, two to five times lower than the
      initial values, were observed at 2 to 4 days. It is concluded that ApoA-I is a
      negative acute-phase protein in pigs.

PMID- 15845531
TI  - Conversion of Staphylococcus epidermidis strains from commensal to invasive by
      expression of the ica locus encoding production of biofilm exopolysaccharide.
AB  - To test if biofilm formation in Staphylococcus epidermidis is dependent on the
      polysaccharide intercellular adhesin, whose biosynthesis is driven by the ica
      locus, a plasmid containing the ica locus was transferred to three ica-negative
      strains. Using in vitro biofilm assays and a rat central venous catheter
      infection model, we confirmed the importance of the ica locus for biofilm
      production and pathogenesis of S. epidermidis.

PMID- 15845532
TI  - The purinergic P2X7 receptor is not required for control of pulmonary
      Mycobacterium tuberculosis infection.
AB  - The importance in vivo of P2X7 receptors in control of virulent Mycobacterium
      tuberculosis was examined in a low-dose aerosol infection mouse model. P2X7(-/-)
      mice controlled infection in lungs as well as wild-type mice, suggesting that the
      P2X7 receptor is not required for control of pulmonary M. tuberculosis infection.

PMID- 15845533
TI  - Gene expression profiling to identify oncogenic determinants of autocrine human
      growth hormone in human mammary carcinoma.
AB  - We have exploited a discrepancy in the oncogenic potential of autocrine and
      exogenous human growth hormone (hGH) in an attempt to identify molecules that
      could potentially be involved in oncogenic transformation of the human mammary
      epithelial cell. Microarray analysis of 19,000 human genes identified a subset of
      305 genes in a human mammary carcinoma cell line that were remarkably different
      in their response to autocrine and exogenous hGH. Autocrine and exogenous hGH
      also regulated 167 common genes. Semiquantitative reverse transcription-PCR
      confirmed differential regulation of genes by either autocrine or exogenous hGH.
      Functional analysis of one of the identified autocrine hGH-regulated genes, TFF3,
      determined that its expression is sufficient to support anchorage-independent
      growth of human mammary carcinoma cells. Small interfering RNA-mediated knockdown
      of TFF3 concordantly abrogated anchorage-independent growth of mammary carcinoma
      cells and abrogated the ability of autocrine hGH to stimulate oncogenic
      transformation of immortalized human mammary epithelial cells. Further functional
      characterization of the identified subset of specifically autocrine hGH regulated
      genes will delineate additional novel oncogenes for the human mammary epithelial
      cell.

PMID- 15845534
TI  - Disease-associated mutations and alternative splicing alter the enzymatic and
      motile activity of nonmuscle myosins II-B and II-C.
AB  - Human families with single amino acid mutations in nonmuscle myosin heavy chain
      (NMHC) II-A (MYH9) and II-C (MYH14) have been described as have mice generated
      with a point mutation in NMHC II-B (MYH10). These mutations (R702C and N93K in
      human NMHC II-A, R709C in murine NMHC II-B, and R726S in human NMHC II-C) result
      in phenotypes affecting kidneys, platelets, and leukocytes (II-A), heart and
      brain (II-B), and the inner ear (II-C). To better understand the mechanisms
      underlying these defects, we characterized the in vitro activity of mutated and
      wild-type baculovirus-expressed heavy meromyosin (HMM) II-B and II-C. We also
      expressed two alternatively spliced isoforms of NMHC II-C which differ by
      inclusion/exclusion of eight amino acids in loop 1, with and without mutations.
      Comparison of the actin-activated MgATPase activity and in vitro motility shows
      that mutation of residues Asn-97 and Arg-709 in HMM II-B and the homologous
      residue Arg-722 (Arg-730 in the alternatively spliced isoform) in HMM II-C
      decreases both parameters but affects in vitro motility more severely. Analysis
      of the transient kinetics of the HMM II-B R709C mutant shows an extremely tight
      affinity of HMM for ADP and a very slow release of ADP from acto-HMM. Although
      mutations generally decreased HMM activity, the R730S mutation in HMM II-C,
      unlike the R730C mutation, had no effect on actin-activated MgATPase activity but
      decreased the rate of in vitro motility by 75% compared with wild type. Insertion
      of eight amino acids into the HMM II-C heavy chain increases both actin-activated
      MgATPase activity and in vitro motility.

PMID- 15845535
TI  - A chaperone pathway in protein disaggregation. Hsp26 alters the nature of protein
      aggregates to facilitate reactivation by Hsp104.
AB  - Cellular protein folding is challenged by environmental stress and aging, which
      lead to aberrant protein conformations and aggregation. One way to antagonize the
      detrimental consequences of protein misfolding is to reactivate vital proteins
      from aggregates. In the yeast Saccharomyces cerevisiae, Hsp104 facilitates
      disaggregation and reactivates aggregated proteins with assistance from Hsp70
      (Ssa1) and Hsp40 (Ydj1). The small heat shock proteins, Hsp26 and Hsp42, also
      function in the recovery of misfolded proteins and prevent aggregation in vitro,
      but their in vivo roles in protein homeostasis remain elusive. We observed that
      after a sublethal heat shock, a majority of Hsp26 becomes insoluble. Its return
      to the soluble state during recovery depends on the presence of Hsp104. Further,
      cells lacking Hsp26 are impaired in the disaggregation of an easily assayed heat
      aggregated reporter protein, luciferase. In vitro, Hsp104, Ssa1, and Ydj1
      reactivate luciferase:Hsp26 co-aggregates 20-fold more efficiently than
      luciferase aggregates alone. Small Hsps also facilitate the Hsp104-mediated
      solubilization of polyglutamine in yeast. Thus, Hsp26 renders aggregates more
      accessible to Hsp104/Ssa1/Ydj1. Small Hsps partially suppress toxicity, even in
      the absence of Hsp104, potentially by sequestering polyglutamine from toxic
      interactions with other proteins. Hence, Hsp26 plays an important role in
      pathways that defend cells against environmental stress and the types of protein
      misfolding seen in neurodegenerative disease.

PMID- 15845536
TI  - tRNA-dependent aminoacyl-adenylate hydrolysis by a nonediting class I aminoacyl
      tRNA synthetase.
AB  - Glutaminyl-tRNA synthetase generates Gln-tRNA(Gln) 10(7)-fold more efficiently
      than Glu-tRNA(Gln) and requires tRNA to synthesize the activated aminoacyl
      adenylate in the first step of the reaction. To examine the role of tRNA in amino
      acid activation more closely, several assays employing a tRNA analog in which the
      2'-OH group at the 3'-terminal A76 nucleotide is replaced with hydrogen
      (tRNA(2'HGln)) were developed. These experiments revealed a 10(4)-fold reduction
      in kcat/Km in the presence of the analog, suggesting a direct catalytic role for
      tRNA in the activation reaction. The catalytic importance of the A76 2'-OH group
      in aminoacylation mirrors a similar role for this moiety that has recently been
      demonstrated during peptidyl transfer on the ribosome. Unexpectedly, tracking of
      Gln-AMP formation utilizing an alpha-32P-labeled ATP substrate in the presence of
      tRNA(2'HGln) showed that AMP accumulates 5-fold more rapidly than Gln-AMP. A cold
      trapping experiment revealed that the nonenzymatic rate of Gln-AMP hydrolysis is
      too slow to account for the rapid AMP formation; hence, the hydrolysis of Gln-AMP
      to form glutamine and AMP must be directly catalyzed by the GlnRS x tRNA(2'HGln)
      complex. This hydrolysis of glutaminyl adenylate represents a novel reaction that
      is directly analogous to the pre-transfer editing hydrolysis of noncognate
      aminoacyl adenylates by editing synthetases such as isoleucyl-tRNA synthetase.
      Because glutaminyl-tRNA synthetase does not possess a spatially separate editing
      domain, these data demonstrate that a pre-transfer editing-like reaction can
      occur within the synthetic site of a class I tRNA synthetase.

PMID- 15845537
TI  - Amino acid-dependent transfer RNA affinity in a class I aminoacyl-tRNA
      synthetase.
AB  - Steady-state and transient kinetic analyses of glutaminyl-tRNA synthetase (GlnRS)
      reveal that the enzyme discriminates against noncognate glutamate at multiple
      steps during the overall aminoacylation reaction. A major portion of the
      selectivity arises in the amino acid activation portion of the reaction, whereas
      the discrimination in the overall two-step reaction arises from very weak binding
      of noncognate glutamate. Further transient kinetics experiments showed that
      tRNA(Gln) binds to GlnRS approximately 60-fold weaker when noncognate glutamate
      is present and that glutamate reduces the association rate of tRNA with the
      enzyme by 100-fold. These findings demonstrate that amino acid and tRNA binding
      are interdependent and reveal an important additional source of specificity in
      the aminoacylation reaction. Crystal structures of the GlnRS x tRNA complex bound
      to either amino acid have previously shown that glutamine and glutamate bind in
      distinct positions in the active site, providing a structural basis for the amino
      acid-dependent modulation of tRNA affinity. Together with other crystallographic
      data showing that ligand binding is essential to assembly of the GlnRS active
      site, these findings suggest a model for specificity generation in which required
      induced-fit rearrangements are significantly modulated by the identities of the
      bound substrates.

PMID- 15845538
TI  - RecQ family members combine strand pairing and unwinding activities to catalyze
      strand exchange.
AB  - RecQ helicases are critical for maintaining genomic integrity. In this study, we
      show that three RecQ members (WRN, deficient in the Werner syndrome; BLM,
      deficient in the Bloom syndrome; and Drosophila melanogaster RecQ5b (dmRecQ5b))
      possess a novel strand pairing activity. Furthermore, each of these enzymes
      combines this strand pairing activity with its inherent DNA unwinding capability
      to perform coordinated strand exchange. In this regard, WRN and BLM are
      considerably more efficient than dmRecQ5b, apparently because dmRecQ5b lacks
      conserved sequences C-terminal to the helicase domain that contribute to DNA
      binding, strand pairing, and strand exchange. Based on our findings, we postulate
      that certain RecQ helicases are structurally designed to accomplish strand
      exchange on complex replication and recombination intermediates. This is highly
      consistent with proposed roles for RecQ members in DNA metabolism and the
      illegitimate recombination and cancer-prone phenotypes associated with RecQ
      defects.

PMID- 15845539
TI  - Involvement of actin in agonist-induced endocytosis of the G protein-coupled
      receptor for thromboxane A2: overcoming of actin disruption by arrestin-3 but not
      arrestin-2.
AB  - The role of actin in endocytosis of G protein-coupled receptors is poorly
      defined. In the present study, we demonstrate that agents that depolymerize
      (latrunculin B and cytochalasin D) or stabilize (jasplakinolide) the actin
      cytoskeleton blocked agonist-induced endocytosis of the beta isoform of the
      thromboxane A(2) receptor (TPbeta) in HEK293 cells. This suggests that
      endocytosis of TPbeta requires active remodeling of the actin cytoskeleton. On
      the other hand, disruption of microtubules with colchicine did not affect
      endocytosis of the receptor. Expression of wild-type and mutant forms of the
      small GTPases RhoA and Cdc42 potently inhibited endocytosis of TPbeta, further
      indicating a role for the dynamic regulation of the actin cytoskeleton in this
      pathway. Agonist treatment of TPbeta in HEK293 cells resulted in the formation of
      actin stress fibers through Galpha(q/11) signaling. Because we previously showed
      that endocytosis of TPbeta is dependent on arrestins, we decided to explore the
      relation between arrestin-2 and -3 and actin in endocytosis of this receptor.
      Interestingly, we show that the inhibition of TPbeta endocytosis by the actin
      toxins in HEK293 cells was overcome by the overexpression of arrestin-3, but not
      of arrestin-2. These results indicate that the actin cytoskeleton is not
      essential in arrestin-3-mediated endocytosis of TPbeta. However, arrestin-3 could
      not promote endocytosis of the TPbetaY339A and TPbetaI343A carboxyl-terminal
      mutants when the actin cytoskeleton was disrupted. Our data provide new evidence
      that the actin cytoskeleton plays an essential role in TPbeta endocytosis.
      Furthermore, our work suggests the existence of actin-dependent and -independent
      arrestin-mediated pathways of endocytosis.

PMID- 15845540
TI  - Hypoxia inhibition of adipocytogenesis in human bone marrow stromal cells
      requires transforming growth factor-beta/Smad3 signaling.
AB  - Although hypoxia and transforming growth factor-beta (TGF-beta) inhibit
      differentiation of adipocytes from preadipocytes and bone marrow-derived cells in
      several species, the relationship between hypoxia and TGF-beta signaling in
      adipocytogenesis is unknown. In this study, we evaluated the mechanisms of
      inhibition of adipocyte differentiation by hypoxia and TGF-beta in human and
      murine marrow stromal cells (MSCs) and the role of TGF-beta/Smad signaling in the
      inhibition of adipocytogenesis by hypoxia. Both hypoxia-mimetic deferoxamine
      mesylate (DFO) and TGF-beta1 inhibited adipocyte differentiation (1.0% versus the
      control at 15 microm DFO and 1.4% versus the control at 1 ng/ml TGF-beta1) and
      adipocyte gene expression (peroxisome proliferator-activated receptor-gamma2 and
      lipoprotein lipase) in human MSCs after 21 days of treatment. Hypoxia (2% O(2))
      and DFO (but not TGF-beta1) increased hypoxia-inducible factor-1alpha as shown by
      Western blotting. Macroarrays and Western and Northern blot analyses showed that
      hypoxia activated the TGF-beta/Smad signaling pathway and that both hypoxia and
      TGF-beta1 modulated adipocyte differentiation pathways such as the insulin-,
      peroxisome proliferator-activated receptor-gamma-, phosphatidylinositol 3-kinase
      , and MAPK-associated signaling pathways. Studies with mouse marrow stromal cell
      lines derived from Smad3(+/+) or Smad3(-/-) mice revealed that the TGF-beta type
      I receptor (ALK-5) and its intracellular signaling molecule Smad3 were necessary
      for the inhibition of adipocyte differentiation by both TGF-beta and hypoxia
      mimetic DFO. Thus, the TGF-beta/Smad signaling pathway is required for hypoxia
      mediated inhibition of adipocyte differentiation in MSCs.

PMID- 15845541
TI  - Selective binding of the scavenger receptor C-type lectin to Lewisx trisaccharide
      and related glycan ligands.
AB  - The scavenger receptor C-type lectin (SRCL) is an endothelial receptor that is
      similar in organization to type A scavenger receptors for modified low density
      lipoproteins but contains a C-type carbohydrate-recognition domain (CRD).
      Fragments of the receptor consisting of the entire extracellular domain and the
      CRD have been expressed and characterized. The extracellular domain is a trimer
      held together by collagen-like and coiled-coil domains adjacent to the CRD. The
      amino acid sequence of the CRD is very similar to the CRD of the
      asialoglycoprotein receptor and other galactose-specific receptors, but SRCL
      binds selectively to asialo-orosomucoid rather than generally to
      asialoglycoproteins. Screening of a glycan array and further quantitative binding
      studies indicate that this selectivity results from high affinity binding to
      glycans bearing the Lewis(x) trisaccharide. Thus, SRCL shares with the dendritic
      cell receptor DC-SIGN the ability to bind the Lewis(x) epitope. However, it does
      so in a fundamentally different way, making a primary binding interaction with
      the galactose moiety of the glycan rather than the fucose residue. SRCL shares
      with the asialoglycoprotein receptor the ability to mediate endocytosis and
      degradation of glycoprotein ligands. These studies suggest that SRCL might be
      involved in selective clearance of specific desialylated glycoproteins from
      circulation and/or interaction of cells bearing Lewis(x)-type structures with the
      vascular endothelium.

PMID- 15845542
TI  - Cyclophilin A binds to linear peptide motifs containing a consensus that is
      present in many human proteins.
AB  - Cyclophilin A (CypA) is a peptidyl-prolyl cis/trans-isomerase that is involved in
      multiple signaling events of eukaryotic cells. It might either act as a catalyst
      for prolyl bond isomerization, or it can form stoichiometric complexes with
      target proteins. We have investigated the linear sequence recognition code for
      CypA by phage display and found the consensus motif FGPXLp to be selected after
      five rounds of panning. The peptide FGPDLPAGD showed inhibition of the isomerase
      reaction and NMR chemical shift mapping experiments highlight the CypA
      interaction epitope. Ligand docking suggests that the peptide was able to bind to
      CypA in the cis- and trans-conformation. Protein Data Bank searches reveal that
      many human proteins contain the consensus motif, and several of these protein
      motifs are shown to interact with CypA in vitro. These sequences represent
      putative target sites for binding of CypA to intracellular proteins.

PMID- 15845543
TI  - The co-chaperone carboxyl terminus of Hsp70-interacting protein (CHIP) mediates
      alpha-synuclein degradation decisions between proteasomal and lysosomal pathways.
AB  - Alpha-synuclein is a major component of Lewy bodies, the pathological hallmark of
      Parkinson disease, dementia with Lewy bodies, and related disorders. Misfolding
      and aggregation of alpha-synuclein is thought to be a critical cofactor in the
      pathogenesis of certain neurodegenerative diseases. In the current study, we
      investigate the role of the carboxyl terminus of Hsp70-interacting protein (CHIP)
      in alpha-synuclein aggregation. We demonstrate that CHIP is a component of Lewy
      bodies in the human brain, where it colocalizes with alpha-synuclein and Hsp70.
      In a cell culture model, endogenous CHIP colocalizes with alpha-synuclein and
      Hsp70 in intracellular inclusions, and overexpression of CHIP inhibits alpha
      synuclein inclusion formation and reduces alpha-synuclein protein levels. We
      demonstrate that CHIP can mediate alpha-synuclein degradation by two discrete
      mechanisms that can be dissected using deletion mutants; the tetratricopeptide
      repeat domain is critical for proteasomal degradation, whereas the U-box domain
      is sufficient to direct alpha-synuclein toward the lysosomal degradation pathway.
      Furthermore, alpha-synuclein, synphilin-1, and Hsp70 all coimmunoprecipitate with
      CHIP, raising the possibility of a direct alpha-synuclein-CHIP interaction. The
      fact that the tetratricopeptide repeat domain is required for the effects of CHIP
      on alpha-synuclein inclusion morphology, number of inclusions, and proteasomal
      degradation as well as the direct interaction of CHIP with Hsp70 implicates a
      cooperation of CHIP and Hsp70 in these processes. Taken together, these data
      suggest that CHIP acts a molecular switch between proteasomal and lysosomal
      degradation pathways.

PMID- 15845544
TI  - Different structural requirements for the constitutive and the agonist-induced
      activities of the beta2-adrenergic receptor.
AB  - We converted Ser-207, located in helix 5 of the beta2-adrenergic receptor, into
      all other natural amino acids. To quantify receptor activation as a receptor
      number-independent parameter and directly related to G(s) activation, we
      expressed the mutants in a G alpha(s)-tethered form. GTP exchange in such
      constructs is restricted to the fused alpha-subunit and is a linear function of
      the receptor concentration. Except S207R, all other mutants were expressed to a
      suitable level for investigation. All mutations reduced the binding affinities of
      the catechol agonists, epinephrine and isoproterenol, and the extent of reduction
      was unrelated to the residue ability to form hydrogen bonds. Instead, both
      enhancements and reductions of affinity were observed for the partial agonist
      halostachin and the antagonist pindolol. The mutations also enhanced and
      diminished ligand-induced receptor activation, but the effects were strictly
      ligand-specific. Polar residues such as Asp and His exalted the activation by
      full agonists but suppressed that induced by the partial agonists halostachin and
      dichloroisoproterenol. In contrast, hydrophobic residues such as Ile and Val
      augmented partial agonist activation. Only Ile and Lys produced a significant
      increase of constitutive activity. The effects on binding and activity were not
      correlated, nor did such parameters show any clear correlation with up to 78
      descriptors of amino acid physicochemical properties. Our data question the idea
      that Ser-207 is exposed to the polar crevice in the unbound receptor. They also
      suggest that the active receptor form induced by a full agonist might be
      substantially different from that caused by constitutive activation.

PMID- 15845545
TI  - Proteolytic cleavage of the p65-RelA subunit of NF-kappaB during poliovirus
      infection.
AB  - Activation of NF-kappaB during viral infection is one of the critical elements in
      innate immune response. Several virus-specific factors, such as double-stranded
      RNA, can trigger host defense mechanisms by inducing NF-kappaB-mediated
      expression of cytokines and interferons. Early stages of poliovirus infection are
      also associated with degradation of IkappaB alpha and translocation of NF-kappaB
      into the nucleus. However, at later stages of poliovirus replication the p65-RelA
      component of the NF-kappaB complex undergoes a specific cleavage that coincides
      with the onset of intensive poliovirus protein synthesis and the appearance of
      the activity of poliovirus protease 3C. Indeed, the p65-RelA amino acid sequence
      contains the recognition site for 3C, and recombinant protein 3C was shown to be
      capable of proteolytic cleavage of p65-RelA, generating truncated product similar
      to that observed during poliovirus infection. Cleavage of p65-RelA occurs during
      replication of ECHO-1 and rhinovirus 14, suggesting that inactivation of NF
      kappaB function by proteolytic cleavage of p65-RelA is the common mechanism by
      which picornaviruses suppress the innate immune response.

PMID- 15845546
TI  - A novel class of dual-family immunophilins.
AB  - Immunophilins are protein chaperones with peptidylprolyl isomerase activity that
      belong to one of two large families, the cyclosporin-binding cyclophilins (CyPs)
      and the FK506-binding proteins (FKBPs). Each family displays characteristic and
      conserved sequence features that differ between the two families. We report a
      novel group of dual-family immunophilins that contain both CyP and FKBP domains
      for which we propose the name FCBP (FK506- and cyclosporin-binding protein). The
      FCBP of Toxoplasma gondii, a protozoan parasite, contained N-terminal FKBP and C
      terminal CyP domains joined by tetratricopeptide repeats. Structure-function
      analysis revealed that both domains were functional and exhibited family-specific
      drug sensitivity. The individual domains of FCBP inhibited calcineurin (protein
      phosphatase 2B) in the presence of the appropriate drugs. In binding studies,
      FCBP recruited calcineurin in the presence of FK506 and a putative target of
      rapamycin homolog in the presence of rapamycin. Two additional FCBP sequences in
      Flavobacterium and one in Treponema (spirochete) were also identified in which
      the CyP and FKBP domains were in the reverse order. T. gondii growth was
      inhibited by cyclosporin and FK506 in a moderately synergistic manner. The
      knockdown of FCBP by RNA interference revealed its essentiality for T. gondii
      growth. Clearly, the FCBPs are novel chaperones and potential targets of multiple
      immunosuppressant drugs.

PMID- 15845547
TI  - A structural basis for CD8+ T cell-dependent recognition of non-homologous
      peptide ligands: implications for molecular mimicry in autoreactivity.
AB  - Molecular mimicry of self-epitopes by viral antigens is one possible pathogenic
      mechanism underlying induction of autoimmunity. A self-epitope, mDBM, derived
      from mouse dopamine beta-mono-oxygenase (KALYDYAPI) sharing 44% sequence identity
      with the lymphocytic choriomeningitis virus-derived immunodominant epitope gp33
      (KAVYNFATC/M), has previously been identified as a cross-reactive self-ligand,
      presentation of which results in autoimmunity. A rat peptide homologue, rDBM
      (KALYNYAPI, 56% identity to gp33), which displayed similar properties to mDBM,
      has also been identified. We herein report the crystal structure of H-2Db.rDBM
      and a comparison with the crystal structures of the cross-reactive H-2Db.gp33 and
      non-cross-reactive H-2Db.gp33 (V3L) escape variant (KALYNFATM, 88% identity to
      gp33). Despite the large sequence disparity, rDBM and gp33 peptides are presented
      in nearly identical manners by H-2Db, with a striking juxtaposition of the
      central sections of both peptides from residues p3 to p7. The structural
      similarity provides H-2Db in complex with either a virus-derived or a dopamine
      beta-mono-oxygenase-derived peptide with a shared antigenic identity that
      conserves the positioning of the heavy chain and peptide residues that interact
      with the T cell receptor (TCR). This stands in contrast to the structure of H
      2Db.gp33 (V3L), in which a single conserved mutation, also present in rDBM,
      induces large movements of both the peptide backbone and the side chains that
      interact with the TCR. The TCR-interacting surfaces of the H-2Db.rDBM and H
      2Db.gp33 major histocompatibility complexes are very similar with regard to
      shape, topology, and charge distribution, providing a structural basis for CD8 T
      cell activation by molecular mimicry and potential subsequent development of
      autoreactivity.

PMID- 15845548
TI  - G protein-coupled receptor activation rapidly stimulates focal adhesion kinase
      phosphorylation at Ser-843. Mediation by Ca2+, calmodulin, and Ca2+/calmodulin
      dependent kinase II.
AB  - A rapid increase in the tyrosine phosphorylation of focal adhesion kinase (FAK)
      has been extensively documented in cells stimulated by multiple signaling
      molecules, but little is known about the regulation of FAK phosphorylation at
      serine residues. Stimulation of Swiss 3T3 cells with the G protein-coupled
      receptor agonists bombesin, vasopressin, or bradykinin induced an extremely rapid
      (within 5 s) increase in FAK phosphorylation at Ser-843. The phosphorylation of
      this residue preceded FAK phosphorylation at Tyr-397, the major
      autophosphorylation site, and FAK phosphorylation at Ser-910. Treatment of intact
      cells with ionomycin stimulated a rapid increase in FAK phosphorylation at Ser
      843, indicating that an increase in intracellular Ca2+ concentration ([Ca2+]i) is
      a potential pathway leading to FAK-Ser-843 phosphorylation. Indeed, treatment
      with agents that prevent an agonist-induced increase in [Ca2+]i (e.g.
      thapsigargin or BAPTA (1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic
      acid)), interfere with calmodulin function (e.g. trifluoperazine, W13, and W7),
      or block Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation (KN93)
      or expression (small interfering RNA) abrogated the rapid FAK phosphorylation at
      Ser-843 induced by bombesin, bradykinin, or vasopressin. Furthermore, activated
      CaMKII directly phosphorylated the recombinant COOH-terminal region of FAK at a
      residue equivalent to Ser-843. Thus, our results demonstrate that G protein
      coupled receptor activation induces rapid FAK phosphorylation at Ser-843 through
      Ca2+, calmodulin, and CaMKII.

PMID- 15845549
TI  - CNK1 is a scaffold protein that regulates Src-mediated Raf-1 activation.
AB  - Raf-1 is a regulator of cellular proliferation, differentiation, and apoptosis.
      Activation of the Raf-1 kinase activity is tightly regulated and involves
      targeting to the membrane by Ras and phosphorylation by various kinases,
      including the tyrosine kinase Src. Here we demonstrate that the connector
      enhancer of Ksr1, CNK1, mediates Src-dependent tyrosine phosphorylation and
      activation of Raf-1. CNK1 binds preactivated Raf-1 and activated Src and forms a
      trimeric complex. CNK1 regulates the activation of Raf-1 by Src in a
      concentration-dependent manner typical for a scaffold protein. Down-regulation of
      endogenously expressed CNK1 by small inhibitory RNA interferes with Src-dependent
      activation of ERK. Thus, CNK1 allows cross-talk between Src and Raf-1 and is
      essential for the full activation of Raf-1.

PMID- 15845550
TI  - Analysis of double-stranded RNA-induced apoptosis pathways using interferon
      response noninducible small interfering RNA expression vector library.
AB  - We have developed an original vector library that allowed us to exploit the
      phenomenon of RNA interference but also allowed us to avoid the confounding
      effects of the interferon response. In the present work, we used our library of
      small interfering RNA expression vectors to examine the genes involved in
      apoptosis that was induced by double-stranded RNA. To our surprise, screening of
      our library revealed two novel double-stranded RNA-induced apoptotic pathways, a
      JNK/SAPK-mediated mitochondrial pathway and an ERK2-related pathway, both of
      which appeared to be independent of the serine-threonine protein kinase-dependent
      caspase pathway. We also found that MST2 and protein kinase Calpha both activated
      the pro-apoptotic signal mediated by ERK2. The results of our screening analysis
      suggested the utility of large scale screenings with libraries of small
      interfering RNA expression vectors.

PMID- 15845551
TI  - The selectivity filter of the cation channel TRPM4.
AB  - Transient receptor potential channel melastatin subfamily (TRPM) 4 and its close
      homologue, TRPM5, are the only two members of the large transient receptor
      potential superfamily of cation channels that are impermeable to Ca(2+). In this
      study, we located the TRPM4 selectivity filter and investigated possible
      structural elements that render it Ca(2+)-impermeable. Based on homology with
      known cation channel pores, we identified an acidic stretch of six amino acids in
      the loop between transmembrane helices TM5 and TM6 ((981)EDMDVA(986)) as a
      potential selectivity filter. Substitution of this six-amino acid stretch with
      the selectivity filter of TRPV6 (TIIDGP) resulted in a functional channel that
      combined the gating hallmarks of TRPM4 (activation by Ca(2+), voltage dependence)
      with TRPV6-like sensitivity to block by extracellular Ca(2+) and Mg(2+) as well
      as Ca(2+) permeation. Neutralization of Glu(981) resulted in a channel with
      normal permeability properties but a strongly reduced sensitivity to block by
      intracellular spermine. Neutralization of Asp(982) yielded a functional channel
      that exhibited extremely fast desensitization (tau < 5 s), possibly indicating
      destabilization of the pore. Neutralization of Asp(984) resulted in a non
      functional channel with a dominant negative phenotype when coexpressed with wild
      type TRPM4. Combined neutralization of all three acidic residues resulted in a
      functional channel whose voltage dependence was shifted toward very positive
      potentials. Substitution of Gln(977) by a glutamate, the corresponding residue in
      divalent cation-permeable TRPM channels, altered the monovalent cation
      permeability sequence and resulted in a pore with moderate Ca(2+) permeability.
      Our findings delineate the selectivity filter of TRPM channels and provide the
      first insight into the molecular basis of monovalent cation selectivity.

PMID- 15845552
TI  - Structural and mutational analysis of Trypanosoma brucei prostaglandin H2
      reductase provides insight into the catalytic mechanism of aldo-ketoreductases.
AB  - Trypanosoma brucei prostaglandin F2alpha synthase is an aldo-ketoreductase that
      catalyzes the reduction of prostaglandin H2 to PGF2alpha in addition to that of
      9,10-phenanthrenequinone. We report the crystal structure of TbPGFS.NADP+.citrate
      at 2.1 angstroms resolution. TbPGFS adopts a parallel (alpha/beta)8-barrel fold
      lacking the protrudent loops and possesses a hydrophobic core active site that
      contains a catalytic tetrad of tyrosine, lysine, histidine, and aspartate, which
      is highly conserved among AKRs. Site-directed mutagenesis of the catalytic tetrad
      residues revealed that a dyad of Lys77 and His110, and a triad of Tyr52, Lys77,
      and His110 are essential for the reduction of PGH2 and 9,10-PQ, respectively.
      Structural and kinetic analysis revealed that His110, acts as the general acid
      catalyst for PGH2 reduction and that Lys77 facilitates His110 protonation through
      a water molecule, while exerting an electrostatic repulsion against His110 that
      maintains the spatial arrangement which allows the formation of a hydrogen bond
      between His110 and C11 that carbonyl of PGH2. We also show Tyr52 acts as the
      general acid catalyst for 9,10-PQ reduction, and thus we not only elucidate the
      catalytic mechanism of a PGH2 reductase but also provide an insight into the
      catalytic specificity of AKRs.

PMID- 15845553
TI  - Noise exposure, awareness, attitudes and use of hearing protection in a steel
      rolling mill in Nigeria.
AB  - OBJECTIVES: To study exposure to noise, the attitudes and knowledge towards noise
      induced hearing loss and the actual use of hearing protection in a steel rolling
      mill in Nigeria. METHODS: A structured questionnaire was administered to 116
      randomly selected workers to collect information relating to their knowledge and
      attitudes towards hazardous occupational noise and preventative measures. Noise
      mapping of the factory was also carried out. RESULTS: Time weighted average noise
      levels were: administrative area 49 dBA, mechanic/maintenance workshop 72 dBA,
      mill floor 86 dBA and finishing stage 93 dBA. There was high awareness of the
      hazard of noise to hearing (93%) and of methods of prevention (92%) but only 27%
      possessed hearing protectors and only 28% of these stated that they used them all
      the time. CONCLUSION: While noise is recognized as a hazard, initiatives are
      required to increase use of effective preventative measures.

PMID- 15845554
TI  - Testing the Job Demand-Control-Support model with anxiety and depression as
      outcomes: the Hordaland Health Study.
AB  - AIM: To test the strain/iso-strain, interaction and buffer hypotheses of the Job
      Demand-Control-Support model in relation to anxiety and depression. METHODS: Five
      thousand five hundred and sixty-two workers with valid Demand-Control-Support
      Questionnaire (DCSQ) scores were examined with the sub-scales of the Hospital
      Anxiety and Depression Scale as outcomes. Multiple statistical methods were
      applied. RESULTS: The strain and iso-strain hypotheses were confirmed. Generally,
      additive and non-interaction effects were found between psychological demands,
      control and social support. The buffer hypotheses were refuted. Results from
      analyses testing different interaction operationalizations were complementary.
      CONCLUSIONS: High demands, low control and low support individually, but
      particularly combined, are risk factors for anxiety and depression. Support is
      the DCSQ index most strongly associated with anxiety and depression in women.
      Assessment of psychosocial work environment may identify workers at risk, and
      serve as a basis for job-redesign.

PMID- 15845555
TI  - Fold recognition aided by constraints from small angle X-ray scattering data.
AB  - We performed a systematic exploration of the use of structural information
      derived from small angle X-ray scattering (SAXS) measurements to improve fold
      recognition. SAXS data provide the Fourier transform of the histogram of atomic
      pair distances (pair distribution function) for a given protein and hence can
      serve as a structural constraint on methods used to determine the native
      conformational fold of the protein. Here we used it to construct a similarity
      based fitness score with which to evaluate candidate structures generated by a
      threading procedure. In order to combine the SAXS scores with the standard energy
      scores and other 1D profile-based scores used in threading, we made use both of a
      linear regression method and of a neural network-based technique to obtain
      optimal combined fitness scores and applied them to the ranking of candidate
      structures. Our results show that the use of SAXS data with gapless threading
      significantly improves the performance of fold recognition.

PMID- 15845557
TI  - Calcium: just another regulator in the machinery of life?
AB  - * BACKGROUND: Current hypotheses imply that stimulus-response systems in plants
      are networks of signal transduction pathways. It is usually assumed that these
      pathways connect receptors with effectors via chains of molecular events. Diverse
      intermediate signalling components (transducers) participate in these processes.
      However, many cellular transducers respond to several stimuli. Hence, there are
      no discrete chains but rather pathways that interconnect network-modules of
      different command structure. In particular, the cytosolic free Ca2+ concentration
      ([Ca2+](cyt)) is thought to perform many different tasks in a wide range of
      cellular events. However, this range of putative functions is so wide that it is
      often questioned how Ca2+ can comply with the definition of a second messenger.
      *THE Ca2+ SIGNATURE HYPOTHESIS: Some authors have suggested the concept of a
      specific signature of the ([Ca2+](cyt)) response. This implies that
      characteristics of the time course of changes in ([Ca2+](cyt)) and their
      localized sites of appearance in cells are used by the plant to identify the type
      and intensity of the stimulus. This hypothesis has triggered many investigations,
      which have yielded contradictory results. * THE CURRENT PICTURE: Much evidence
      suggests that the functions of calcium can be grouped into three classes: Ca2+ as
      a protective agent, Ca2+ as a chemical switch and Ca2+ as a 'digital' information
      carrier. Examples of the first two classes are presented here. The third is more
      controversial; while some investigations seem to support this idea, others call
      the Ca2+ signature hypothesis into question. Further investigations are needed to
      shed more light on Ca(2+)-driven signalling cascades.

PMID- 15845558
TI  - Measurement of albuminuria during acute myocardial infarction and its relation
      with prognosis.

PMID- 15845559
TI  - Pre-operative atrial fibrillation as the key determinant of outcome of mitral
      valve repair for degenerative mitral regurgitation.
AB  - AIMS: To examine the impact of pre-operative atrial fibrillation (AF) on the
      outcome of mitral valve repair (MVR) for degenerative mitral regurgitation (MR).
      METHODS AND RESULTS: Among 392 patients with moderate to severe MR who underwent
      MVR between 1991 and 2002, 283 patients with isolated degenerative MR were
      followed for 4.7+/-3.3 years. Of 27 deaths, nine were due to cardioembolic events
      and four were due to left ventricular (LV) dysfunction. When compared with
      patients with pre-operative AF, those with sinus rhythm (SR) had better survival
      (96+/-2.1 vs. 87+/-3.2% at 5 years, P=0.002) and higher cardiac event-free rates
      (96+/-2.0 vs. 75+/-4.4% at 5 years, P<0.001). In patients with pre-operative SR,
      observed and expected survival were similar (P=0.811). Cox multivariable
      regression analysis confirmed AF [P=0.027, adjusted hazard ratio (AHR) 2.9] and
      age as independently predictive of survival, and AF (P=0.002, AHR 3.1), New York
      Heart Association Class, and LV fractional shortening as independently predictive
      of cardiac event. CONCLUSION: Death due to LV dysfunction was not frequent and
      cardioembolic events due to AF were the leading cause for cardiac death. Pre
      operative AF became a strong independent predictor of survival and morbidity.
      Patients with pre-operative SR had excellent prognosis. The benefits of
      preventing cardioembolic events due to AF validate the indication of MVR for
      patients with high risk for AF.

PMID- 15845560
TI  - Effects of insulin on left ventricular function during dynamic exercise in
      overweight and obese subjects.
AB  - AIMS: We designed this study in order to determine the effect of insulin on
      cardiac function in overweight and obese subjects during exercise. METHODS AND
      RESULTS: The cardiac function of 62 normal glucose tolerant subjects, aged 30-40
      and divided into normal weight (group 1, n=22, BMI 20-24.9 kg/m(2)), overweight
      (group 2, n=20, BMI 25-29.9 kg/m(2)), and obesity (group 3, n=20, BMI 30-35
      kg/m(2)) was evaluated at rest and during dynamic exercise through
      angiocardioscintigraphy, when on hyperinsulinaemic euglycaemic clamp (test A) and
      when on normal saline infusion (test B). Left ventricular function at rest was
      statistically greater (P<0.05) in both tests in overweight and obese subjects
      compared with normal weight controls, with no statistical difference (P=0.057)
      within groups between insulin and normal saline infusion. During exercise,
      cardiac function improved in all the subjects in both tests. The increase was
      lower in overweight and obese patients, even if statistically significant only in
      obese vs. control subjects in both tests (P<0.05). Insulin sensitivity showed a
      significant correlation (P< or =0.001) with left ventricular ejection fraction
      (LVEF) at rest and with change in LVEF during clamp. CONCLUSION: Our findings
      suggest a metabolic pathogenesis for the impaired LV function in obesity.

PMID- 15845561
TI  - Symptom association probability and symptom sensitivity index: preferable but
      still suboptimal predictors of response to high dose omeprazole.
AB  - BACKGROUND: Twenty four hour oesophageal pH monitoring is frequently used to
      quantify the association between a patient's symptom and gastro-oesophageal
      reflux. Three indices (symptom association probability (SAP), symptom index (SI),
      and symptom sensitivity index (SSI)) are used to quantify and establish this
      relation. AIMS: The aim of the present study was to compare these indices against
      the omeprazole test (OT) as an objective indicator of reflux induced symptoms.
      METHODS: Fifty two patients with a predominant symptom of heartburn were enrolled
      from gastroenterology and primary care clinics. Baseline symptom score was
      calculated at the fist visit. All patients underwent 24 hour oesophageal pH
      monitoring, and symptom-reflux association indices were calculated. All patients
      were placed on high dose omeprazole (40 mg in the morning, 20 mg at night) after
      completion of pH monitoring and symptom score was recorded again after one week.
      RESULTS: Thirty eight patients completed the study. All three indices were
      significantly related to each other (p<0.001). SAP and SSI (with a new cut off of
      1.3, but not with the commonly used 5%) had statistically significant relations
      with OT (p<0.05 for both). SSI had the highest positive and negative predictive
      values and sensitivity. The specificity of SSI and SAP was equal and lower than
      SI. Areas under the receiver operating characteristic (ROC) curve for the three
      indices were not significantly different from each other or from a hypothetical
      non-discriminating test. Per cent time pH <4, sex, and age had no relation to OT
      and no effect on its correlation with association indices. No cut off point could
      be found at which the results of SI could be related significantly to the OT
      results. CONCLUSION: SAP and SSI are significantly related to symptomatic
      response to high dose omeprazole; however, they are far from perfect, with a
      significant number of discordant cases as well as relatively small areas under
      the ROC curves. We suggest that the new cut off of 1.3 be used for SSI in the
      future. Further research is needed to identify possible methods to improve the
      discrimination power of these indices or to identify possible patient
      characteristics that may affect this relation.

PMID- 15845562
TI  - Family history and molecular features of children, adolescents, and young adults
      with colorectal carcinoma.
AB  - BACKGROUND: Colorectal cancer is extremely rare in childhood. Published case
      series reporting children and adolescents with colorectal cancer have not focused
      on the underlying genetic aspects of the tumour or genetic susceptibility of the
      families. AIMS: We examined a cohort of patients with early onset colorectal
      cancer to determine whether a specific genetic predisposition could be
      elucidated. In particular, we focused on whether DNA mismatch repair gene
      deficiency which causes hereditary non-polyposis colorectal cancer (HNPCC) could
      be elucidated. METHODS: Patients with colorectal cancer </=24 years of age were
      identified from a database at the Familial Gastrointestinal Cancer Registry at
      Mount Sinai Hospital, Toronto. Detailed pedigrees were ascertained from the
      proband or parents. Tumours were tested for microsatellite instability, a
      hallmark of HNPCC. Germline mismatch repair gene mutations (MSH2 and MLH1) were
      sought in some cases. Clinical data were obtained by chart audit. RESULTS: Among
      1382 probands in our registry, 16 (1%) colorectal cancer patients were 24 years
      or younger at the time of diagnosis. Microsatellite instability was identified in
      tumours from eight (73%) of 11 evaluated patients. Germline mutations in mismatch
      repair genes were identified in six of 12 patients, including MSH2 (n = 3), MLH1
      (n = 2), and PMS2 (n = 1). Ten (63%) of 16 families met the Amsterdam criteria
      for HNPCC. Among these, six were screened for mismatch repair gene mutations and
      three were found to carry MSH2 or MLH1 germline mutations. Location of the
      colorectal cancers included rectum/sigmoid (n = 9), splenic flexure (n = 2),
      hepatic flexure (n = 3), and caecum (n = 2). Forty four per cent (7/16) of these
      young cases developed additional malignancies (gastrointestinal (n = 8) and
      extraintestinal (n = 4)) during follow up (mean 12.8 (SD 12.4) years (range 0.08
      30)). CONCLUSIONS: Patients with early onset colorectal carcinoma often have an
      inherited predisposition to the disease. Tumours with high frequency
      microsatellite instability and germline mutations of mismatch repair genes are
      sufficiently common in this patient population that they should be considered,
      even though family histories may not satisfy the stringent Amsterdam criteria for
      HNPCC. Young colorectal cancer patients are at increased risk of developing
      second gastrointestinal and extraintestinal malignancies.

PMID- 15845564
TI  - Phase I trial of weekly docetaxel and concurrent radiotherapy for head and neck
      cancer in elderly patients or patients with complications.
AB  - OBJECTIVE: We planned a phase I study of radiotherapy combined with weekly
      docetaxel for elderly patients or patients with complications to find out the
      optimal dose. METHODS: Five consecutive weekly administrations of docetaxel were
      accompanied by radiotherapy for patients diagnosed with squamous cell carcinoma
      of the head and neck. The starting dose of docetaxel was 10 mg/m(2) with
      escalation at 2 mg/m(2) per step. RESULTS: Fifteen patients were enrolled in this
      trial. The maximal tolerated dose was 14 mg/m(2), so the recommended dose was
      determined as 12 mg/m(2). Hematological toxicity was sufficiently weak. Common
      dose-limiting toxicity was stomatitis within the radiation field. CONCLUSIONS:
      This protocol was thought to be practical for elderly patients or those with
      medical complications.

PMID- 15845563
TI  - Key role of the sympathetic microenvironment for the interplay of tumour necrosis
      factor and interleukin 6 in normal but not in inflamed mouse colon mucosa.
AB  - BACKGROUND: In the intestinal tract, the role of sympathetic neurotransmitters
      has been largely ignored in mucosal neuroimmunology. AIM: Our aim was to
      investigate the influence of the sympathetic microenvironment on the mucosal
      interplay of tumour necrosis factor (TNF) and interleukin 6 (IL-6). METHODS:
      Colon strips of normal and colitic BALB/c mice were superfused in vitro. Tissue
      was electrically stimulated to investigate the influence of endogenous
      norepinephrine (NE) on secretion of IL-6, with or without anti-TNF antibodies
      (anti-TNF) and adrenoceptor antagonists. IL-6 was secreted from macrophages.
      RESULTS: Superfusion with anti-TNF stimulated IL-6 secretion in normal but not in
      colitic colon (p<0.005). Parallel superfusion with a beta-adrenergic antagonist
      abrogated this phenomenon. Anti-TNF increased release of NE from normal colonic
      strips (p<0.05), which demonstrates TNF induced inhibition of preterminal NE
      release. In colitic mice, anti-TNF did not change NE release. In the presence of
      anti-TNF, exogenous and endogenous NE stimulated colonic IL-6 secretion via beta
      adrenoceptors in normal (p<0.001) but not in colitic mice. In the absence of anti
      TNF, endogenous and exogenous NE inhibited IL-6 secretion via the beta
      adrenoceptor in normal but not in colitic mice (p<0.01). Colitic mice
      demonstrated loss of sympathetic nerve fibres. CONCLUSIONS: Modulation of mucosal
      IL-6 is largely dependent on the sympathetic microenvironment and availability of
      local TNF in normal but not in colitic mice. Anti-TNF strategies may lead to an
      increase in the proinflammatory cytokine depending on adrenergic tone. This would
      be relevant with normal sympathetic innervation, which is lost in colitic mice.
      We present a model of sympathetic regulation of colonic macrophage TNF and IL-6
      secretion.

PMID- 15845565
TI  - Trends in lung cancer mortality among young adults in Japan.
AB  - BACKGROUND: Trends in lung cancer mortality among young adults, which are
      important for projecting future trends, have not been explored previously in
      Japan. METHODS: Using data from the National Vital Statistics between 1958 and
      2003, we compiled lung cancer mortality by sex and 5-year birth cohort among
      young adults aged 20-49. RESULTS: Mortality among those aged 20-29 has
      consistently decreased regardless of sex. There were birth cohort effects in
      mortality from lung cancer, although these were less evident among women than
      among men. Both men and women born in the 1930s had lower mortality rates, while
      those born after 1940 had higher lung cancer mortality rates. Mortality rates
      appear to be declining for male birth cohorts born after 1950 and female birth
      cohorts after 1960, although these trends may not be stable due to the small
      number of deaths in these cohorts. CONCLUSION: Lung cancer mortality trends
      appear to be decreasing among young adults. This might be associated with the
      lower mortality of birth cohorts after 1950 for men and the 1960s birth cohorts
      for women. Careful monitoring is needed to confirm continuation of these
      declining trends.

PMID- 15845567
TI  - Phase II study of carboplatin-paclitaxel combination chemotherapy in elderly
      patients with advanced non-small cell lung cancer.
AB  - BACKGROUND: More than 30% of cases of non-small cell lung cancer (NSCLC) arise in
      patients aged > or =70 years. The efficacy and safety of carboplatin-paclitaxel
      combination chemotherapy in elderly patients with advanced NSCLC were evaluated
      in a phase II trial. METHODS: Twenty-five patients aged > or =70 years (median,
      76; range, 70-83) with chemotherapy-naive advanced NSCLC were enrolled between
      January 2001 and July 2003. Additional criteria included the presence of
      measurable lesions, an Eastern Cooperative Oncology Group performance status of 0
      or 1, and adequate organ function. Patients received carboplatin at an area under
      the curve of 5 mg/ml/min and paclitaxel at 180 mg/m(2) on the first day of
      consecutive 3 week periods. RESULTS: The patients included four with stage IIIB,
      19 with stage IV and two with recurrent disease. The median number of treatment
      cycles was three (range, 1-4). One complete response and six partial responses,
      yielding an objective response rate of 28%, were obtained. The median survival
      time was 12.3 months and the 1-year survival rate was 52%. Hematological
      toxicities of grade 3 or 4 included leukopenia (40%), neutropenia (68%) and
      anemia (4%). Non-hematological toxicities of grade 3 included arthralgia-myalgia
      (16%) and neuropathy (12%). The objective response rate for patients aged > or
      =75 years (n = 15) was 26%, and no evidence of excessive toxicity in these
      patients was apparent compared with those aged <75 years. CONCLUSION: The
      combination carboplatin-paclitaxel at these doses is a feasible treatment option
      with a favorable toxicity profile for fit elderly patients with advanced NSCLC.

PMID- 15845566
TI  - A phase I/II study comparing regimen schedules of gemcitabine and docetaxel in
      Japanese patients with stage IIIB/IV non-small cell lung cancer.
AB  - OBJECTIVE: Gemcitabine and docetaxel are non-platinum agents with activity in non
      small cell lung cancer (NSCLC). This study was conducted to determine and
      evaluate the recommended regimen of gemcitabine-docetaxel and evaluated its
      efficacy and safety in chemonaive Japanese NSCLC patients. METHODS: In phase I,
      patients with stage IIIB/IV NSCLC were randomized and received either gemcitabine
      on days 1 and 8 plus docetaxel on day 1 or gemcitabine on days 1 and 8 plus
      docetaxel on day 8. The recommended regimen was the dose level preceding the
      maximum tolerated dose; once determined, patients were enrolled in phase II.
      Efficacy and toxicity were evaluated in all patients. RESULTS: Twenty-five
      patients were enrolled in phase I and six patients were given the recommended
      regimen; gemcitabine 1000 mg/m(2) on days 1 and 8 plus docetaxel 50 mg/m(2) on
      day 8. An additional 34 patients were enrolled into phase II and administered
      with the recommended regimen. The response rate was 32.2% [95% confidence
      interval (CI) 20.6-45.6%] overall and 30.0% (95% CI 16.6-46.5%) in patients with
      the recommended regimen (40 patients). Although grade 3 interstitial pneumonia
      was observed in two patients (5.0%) who received the recommended regimen, both
      recovered shortly after steroid treatment. No unexpected events were observed
      throughout this study. CONCLUSIONS: Gemcitabine 1000 mg/m(2) on days 1 and 8 plus
      docetaxel 50 mg/m(2) on day 8 has comparable efficacy and more tolerable
      toxicities than previously reported platinum-based regimens. These results should
      be verified by a phase III study.

PMID- 15845568
TI  - Standard thoracic radiotherapy with or without concurrent daily low-dose
      carboplatin in elderly patients with locally advanced non-small cell lung cancer:
      a phase III trial of the Japan Clinical Oncology Group (JCOG9812).
AB  - BACKGROUND: The purpose of this study was to evaluate whether radiotherapy with
      carboplatin would result in longer survival than radiotherapy alone in elderly
      patients with unresectable stage III non-small cell lung cancer (NSCLC). METHODS:
      Eligible patients were 71 years of age or older with unresectable stage III
      NSCLC. Patients were randomly assigned to the radiotherapy alone (RT) arm,
      irradiation with 60 Gy; or the chemoradiotherapy (CRT) arm, the same radiotherapy
      and additional concurrent use of carboplatin 30 mg/m(2) per fraction up to the
      first 20 fractions. RESULTS: This study was terminated early when 46 patients
      were registered from November 1999 to February 2001. Four patients (one in the RT
      arm, three in the CRT arm) were considered to have died due to treatment-related
      causes. The JCOG Radiotherapy Committee assessed these treatment-related deaths
      (TRDs) and the compliance with radiotherapy in this trial. They found that 60% of
      the cases corresponded to protocol deviation and 7% were protocol violation in
      dose constraint to the normal lung, two of whom died due to radiation
      pneumonitis. As to the effectiveness for the 46 patients enrolled, the median
      survival time was 428 days [95% confidence interval (CI) = 212-680 days] in the
      RT arm versus 554 days (95% CI = 331 to not estimable) in the CRT arm.
      CONCLUSIONS: Due to the early termination of this study, the effectiveness of
      concurrent use of carboplatin remains unclear. We re-planned and started a study
      with an active quality control program which was developed by the JCOG
      Radiotherapy Committee.

PMID- 15845569
TI  - Different manifestations of malignant melanoma in the breast: a report of 12
      cases and a review of the literature.
AB  - BACKGROUND: The breast is associated with a large number of diseases. Besides
      being the host of many benign and malignant tumors, breast skin and parenchyma
      are also metastatic sites for various tumors such as leukemia, lung cancer and
      melanoma. METHODS: Malign melanoma has different manifestations in the breast.
      All these manifestations are important not only as initial presentations of the
      disease, but also as indicators of the progression period of the disease.
      RESULTS: This study reports on 12 cases of cutaneous malignant melanoma in breast
      skin and tissue. Nine of these cases are primary cutaneous melanomas, while the
      others are breast metastases from a distant site cutaneous melanoma. In two of
      the nine primary cutaneous melanomas in-transit metastasis to the breast
      developed during the follow-up period. CONCLUSIONS: In this paper, the diagnostic
      and surgical approach to primary and metastatic melanoma of the breast, and the
      importance of the breast during the follow-up period are reviewed.

PMID- 15845570
TI  - Hypoxia-inducible factor-1alpha is associated with risk of aggressive behavior
      and tumor angiogenesis in gastrointestinal stromal tumor.
AB  - BACKGROUND: The objective of this study was to evaluate the relationship of HIF
      1alpha expression and tumor angiogenesis, recurrence/distant metastasis, and its
      value in the prediction of aggressive behavior of gastrointestinal stromal tumor
      (GIST). METHODS: Paraffin-embedded specimens from 62 patients with GIST were
      divided into two groups, low risk (n = 31) and high risk (n = 31) according to
      the tumor size, mitotic count and proliferating cell nuclear antigen (PCNA)
      index. We investigated the expression of the HIF-1alpha and analyzed correlation
      with tumor angiogenesis monitored by expression of vascular endothelial growth
      factor (VEGF) and tumor microvessel density using immunohistochemical staining.
      The data were analyzed with chi(2) test or Fisher's exact test and multivariate
      test. RESULTS: There were statistically significant differences between high risk
      (29/31; 93.5%) and low risk (8/31; 25.8%) of GIST in high expression of HIF
      1alpha (P<0.0001). In addition, the incidence of recurrence/distant metastasis
      was significantly higher in cases of high HIF-1alpha expression (12/35; 34.3%)
      than in cases of low HIF-1alpha expression (1/24; 4.2%)(P = 0.009). Moreover,
      high VEGF expression (37/43; 86.0%) and microvessel density (30/32; 93.8%) were
      significantly higher in high HIF-1alpha expression tumors than in low-expression
      tumors (P < 0.0001). CONCLUSIONS: Our findings suggest that HIF-1alpha may play
      an important role in aggressive behavior and tumor angiogenesis in GIST. In
      addition, high expression of HIF-1alpha was significantly correlated with tumor
      recurrence/distant metastasis, so it may provide an ancillary prognostic factor
      for GIST.

PMID- 15845571
TI  - Phase II study of irinotecan, 5-fluorouracil and leucovorin as first-line therapy
      for advanced colorectal cancer.
AB  - BACKGROUND: We evaluated the efficacy and tolerability of a modified biweekly
      irinotecan, 5-fluorouracil and leucovorin regimen (modified Douillard regimen) as
      the first-line therapy in patients with advanced colorectal cancer. METHODS: A
      total of 80 patients (41 male, 39 female) with recurrent or metastatic colorectal
      cancer were enrolled between April 2001 and December 2003. The treatment cycle
      consisted of irinotecan 150 mg/m(2) as a 90 min infusion on day 1, leucovorin 20
      mg/m(2) intravenous bolus, immediately followed by a 48 h continuous infusion of
      5-fluorouracil 3000 mg/m(2) on day 1. The primary end-point was response rate,
      and the secondary end-points were time to progression and toxicity profile.
      RESULTS: An overall objective response rate of 38.7% [95% confidence interval
      (CI) 27.84-49.66%] was achieved. The median time to progression was 6.1 months
      (95% CI 4.63-7.57 months) and the median overall survival time was 20.2 months
      (95% CI 15.50-24.90 months). The median duration of follow-up for patients was
      16.9 months. The toxicity profile was more favorable than for the conventional
      Douillard regimen. CONCLUSION: We conclude that the modified Douillard regimen
      may be a practical and more tolerable treatment option in patients with advanced
      colorectal cancer.

PMID- 15845572
TI  - Inflammatory pseudotumor of the liver in a patient with early gastric cancer: CT
      histopathological correlation.
AB  - A case of inflammatory pseudotumor (IPT) of the liver associated with early
      gastric cancer is reported. Intravenous contrast-enhanced computed tomography
      (CT) showed a large, irregularly shaped mass lesion in the left lobe of the
      liver. The lesion was characterized by peripheral rim-like or septal enhancement
      and an internal low density area in the delayed phase. The gastric cancer was a
      papillary adenocarcinoma limited to the mucosa. The resected liver tumor measured
      5.5 x 5.0 x 4.0 cm, and its cut surface revealed a well-circumscribed mass
      divided into lobules by fibrous tissue. Histologically the mass was composed of
      fibrous areas and cellular areas, and the cellular areas consisted of fascicles
      of plump spindle cells intermingled with varying numbers of plasma cells,
      lymphocytes and histiocytes. Thus, the higher attenuation on the enhanced CT scan
      corresponded to the areas of intense fibrosis, and the areas of lower attenuation
      corresponded to the predominantly cellular areas. The CT findings of delayed
      peripheral rim-like or septal enhancement of the hepatic tumor may be a specific
      finding of IPT.

PMID- 15845573
TI  - A long surviving case of Pseudomeigs' syndrome caused by Krukenberg tumor of the
      stomach.
AB  - Meigs syndrome is defined as the triad of benign ovarian tumor with ascites and
      pleural effusion that resolve after resection of the tumor. Pseudomeigs' syndrome
      is a serious disease characterized by malignant ovarian tumor, but ascites and
      hydrothorax usually reveal no malignant cells. Here, we report a 47-year-old pre
      menapausal female patient with cardia cancer. Nearly 14 months after D3
      dissection, she developed Krukenberg tumors on both ovaries causing a
      Pseudomeigs' syndrome with benign ascites and right hydrothorax, which resolved
      dramatically after resection of the tumors and rectouterine pouch peritonectomy.
      She survived nearly 3 years after metastasectomy with a total survival of 46
      months. The patient died because of massive liver metastases. The present case
      suggests that Pseudomeigs' syndrome should be considered in patients with
      Krukenberg tumors, ascites and hydrothorax and that resection of the tumors may
      bring long-term palliation.

PMID- 15845574
TI  - Comparison of cancer mortality (rectal cancer) in five countries: France, Italy,
      Japan, UK and USA from WHO mortality database (1960-2000).

PMID- 15845575
TI  - Theta-burst repetitive transcranial magnetic stimulation suppresses specific
      excitatory circuits in the human motor cortex.
AB  - In four conscious patients who had electrodes implanted in the cervical epidural
      space for the control of pain, we recorded corticospinal volleys evoked by single
      pulse transcranial magnetic stimulation (TMS) over the motor cortex before and
      after a 20 s period of continuous theta-burst stimulation (cTBS). It has
      previously been reported that this form of repetitive TMS reduces the amplitude
      of motor-evoked potentials (MEPs), with the maximum effect occurring at 5-10 min
      after the end of stimulation. The present results show that cTBS preferentially
      decreases the amplitude of the corticospinal I1 wave, with approximately the same
      time course. This is consistent with a cortical origin of the effect on the MEP.
      However, other protocols that lead to MEP suppression, such as short-interval
      intracortical inhibition, are characterized by reduced excitability of late I
      waves (particularly I3), suggesting that cTBS suppresses MEPs through different
      mechanisms, such as long-term depression in excitatory synaptic connections.

PMID- 15845576
TI  - Cytoskeletal regulation of calcium-permeable cation channels in the human
      syncytiotrophoblast: role of gelsolin.
AB  - The human syncytiotrophoblast (hST) is the most apical epithelial barrier that
      covers the villous tree of the human placenta. An intricate and highly organized
      network of cytoskeletal structures supports the hST. Recently, polycystin-2
      (PC2), a TRP-type nonselective cation channel, was functionally observed in hST,
      where it may be an important player to Ca2+ transport. Little is known, however,
      about channel regulation in hST. In this report, the regulatory role of actin
      dynamics on PC2 channels reconstituted from hST apical membranes was explored.
      Acute addition of cytochalasin D (CD, 5 microg ml-1) to reconstituted hST apical
      membranes transiently increased K+ -permeable channel activity. The actin-binding
      proteins alpha-actinin and gelsolin, as well as PC2, were observed by Western
      blot and immunofluorescence analyses in hST vesicles. CD treatment of hST
      vesicles resulted in a re-distribution of actin filaments, in agreement with the
      effect of CD on K+ channel activity. In contrast, addition of exogenous monomeric
      actin, but not prepolymerized actin, induced a rapid inhibition of channel
      function in hST. This inhibition was obliterated by the presence of CD in the
      medium. The acute (<15 min) CD stimulation of K+ channel activity was mimicked by
      addition of the actin-severing protein gelsolin in the presence, but not in the
      absence, of micromolar Ca2+. Ca2+ transport through PC2 triggers a regulatory
      feedback mechanism, which is based on the severing and re-formation of
      filamentous actin near the channels. Cytoskeletal structures may thus be relevant
      to ion transport regulation in the human placenta.

PMID- 15845577
TI  - Unmasking group III metabotropic glutamate autoreceptor function at excitatory
      synapses in the rat CNS.
AB  - Presynaptic group III metabotropic glutamate receptor (mGluR) activation by
      exogenous agonists (such as L-2-amino-4-phosphonobutyrate (L-AP4)) potently
      inhibit transmitter release, but their autoreceptor function has been questioned
      because endogenous activation during high-frequency stimulation appears to have
      little impact on synaptic amplitude. We resolve this ambiguity by studying
      endogenous activation of mGluRs during trains of high-frequency synaptic stimuli
      at the calyx of Held. In vitro whole-cell patch recordings were made from medial
      nucleus of the trapezoid body (MNTB) neurones during 1 s excitatory postsynaptic
      current (EPSC) trains delivered at 200 Hz and at 37 degrees C. The group III
      mGluR antagonist (R,S)-cyclopropyl-4-phosphonophenylglycine (CPPG, 300 microm)
      had no effect on EPSC short-term depression, but accelerated subsequent recovery
      time course (tau: 4.6 +/- 0.8 s to 2.4 +/- 0.4 s, P = 0.02), and decreased paired
      pulse ratio from 1.18 +/- 0.06 to 0.97 +/- 0.03 (P = 0.01), indicating that mGluR
      activation reduced release probability (P). Modelling autoreceptor activation
      during repetitive stimulation revealed that as P declines, the readily releasable
      pool size (N) increases so that the net EPSC (NP) is unchanged and short-term
      depression proceeds with the same overall time course as in the absence of
      autoreceptor activation. Thus, autoreceptor action on the synaptic response is
      masked but the synapse is now in a different state (lower P, higher N). While
      vesicle replenishment clearly underlies much of the recovery from short-term
      depression, our results show that the recovery time course of P also contributes
      to the reduced response amplitude for 1-2 s. The results show that passive
      equilibration between N and P masks autoreceptor modulation of the EPSC and
      suggests that mGluR autoreceptors function to change the synaptic state and
      distribute metabolic demand, rather than to depress synaptic amplitude.

PMID- 15845578
TI  - Inhibition of sarcoplasmic reticular function by chronic interleukin-6 exposure
      via iNOS in adult ventricular myocytes.
AB  - Interleukin (IL)-6 has been shown to decrease cardiac contractility via a nitric
      oxide synthase (NOS)-dependent pathway during acute exposure. We previously
      reported that IL-6 decreases contractility and increases inducible NOS (iNOS) in
      adult rat ventricular myocytes (ARVM) after 2 h exposure. The goal of this study
      was to investigate the cellular mechanism underlying this chronic IL-6-induced
      negative inotropy and the role of iNOS. Pretreatment for 2 h with 10 ng ml-1 IL-6
      decreased the kinetics of cell shortening (CS) and contractile responsiveness to
      Ca2+o ([Ca2+]o from(0) to 2 mM) in ARVM. We first examined whether IL-6 reduced
      Ca2+ influx via L-type Ca2+ -channel current (ICa,L). Whole-cell ICa,L in ARVM
      was measured under conditions similar to those used for CS measurements, and it
      was found to be unaltered by IL-6. The sarcoplasmic reticular (SR) function was
      then assessed by examining postrest potentiation (PRP) and caffeine
      responsiveness of CS. Results showed that treatment with IL-6 for 2 h
      significantly decreased PRP, which was concomitant with a decrease in the
      phosphorylation of phospholamban. Following removal of IL-6, PRP and
      responsiveness to 10 mM caffeine were also reduced. Meanwhile, the IL-6-induced
      increase in nitric oxide (NO) production after 2 h (but not 1 h) was abolished by
      NG-monomethyl-l-arginine (l-NMMA) and 2-amino-5,6-dihydro-6-methyl-4H-1,3
      thiazine (AMT; a selective inhibitor of iNOS). Furthermore, IL-6-elicited
      suppressions of PRP and responsiveness to caffeine and Ca2+o were abolished by L
      NMMA and AMT. Thus, these results suggest that activation of iNOS mediates IL-6
      induced inhibition of SR function in ARVM during chronic exposure.

PMID- 15845579
TI  - Dynamic synapses as archives of synaptic history: state-dependent redistribution
      of synaptic efficacy in the rat hippocampal CA1.
AB  - Plastic modifications of synaptic strength are putative mechanisms underlying
      information processing in the brain, including memory storage, signal integration
      and filtering. Here we describe a dynamic interplay between short-term and long
      term synaptic plasticity. At rat hippocampal CA1 synapses, induction of both long
      term potentiation (LTP) and depression (LTD) was accompanied by changes in the
      profile of short-term plasticity, termed redistribution of synaptic efficacy
      (RSE). RSE was presynaptically expressed and associated in part with a persistent
      alteration in hyperpolarization-activated I(h) channel activity. Already
      potentiated synapses were still capable of showing RSE in response to additional
      LTP-triggering stimulation. Strikingly, RSE took place even after reversal of LTP
      or LTD, that is, the same synapse can display different levels of short-term
      plasticity without changing synaptic efficacy for the initial spike in burst
      presynaptic firing, thereby modulating spike transmission in a firing rate
      dependent manner. Thus, the history of long-term synaptic plasticity is
      registered in the form of short-term plasticity, and RSE extends the information
      storage capacity of a synapse and adds another dimension of functional complexity
      to neuronal operations.

PMID- 15845580
TI  - Different kinetic properties of two T-type Ca2+ currents of rat reticular
      thalamic neurones and their modulation by enflurane.
AB  - Currents arising from T-type Ca2+ channels in nucleus reticularis thalami (nRT)
      play a critical role in generation of low-amplitude oscillatory bursting
      involving mutually interconnected cortical and thalamic neurones, and are
      implicated in the state of arousal and sleep, as well as seizures. Here we show
      in brain slices from young rats that two kinetically different T-type Ca2+
      currents exist in nRT neurones, with a slowly inactivating current expressed only
      on proximal dendrites, and fast inactivating current predominantly expressed on
      soma. Nickel was about twofold more potent in blocking fast (IC50 64 microM) than
      slow current (IC50 107 microM). The halogenated volatile anaesthetic enflurane
      blocked both currents, but only the slowly inactivating current was affected in
      voltage-dependent fashion. Slow dendritic current was essential for generation of
      low-threshold Ca2+ spikes (LTS), and both enflurane and nickel also suppressed
      LTS and neuronal burst firing at concentrations that blocked isolated T currents.
      Differential kinetic properties of T currents expressed in cell soma and proximal
      dendrites of nRT neurones indicate that various subcellular compartments may
      exhibit different membrane properties in response to small membrane
      depolarizations. Furthermore, since blockade of two different T currents in nRT
      neurones by enflurane and other volatile anaesthetics occurs within
      concentrations that are relevant during clinical anaesthesia, our findings
      suggest that these actions could contribute to some important clinical effects of
      anaesthetics.

PMID- 15845581
TI  - Role of extracellular Ca2+ in gating of CaV1.2 channels.
AB  - We examined changes in ionic and gating currents in Ca(V)1.2 channels when
      extracellular Ca(2+) was reduced from 10 mm to 0.1 microm. Saturating gating
      currents decreased by two-thirds (K(D) approximately 40 microm) and ionic
      currents increased 5-fold (K(D) approximately 0.5 microm) due to increasing Na(+)
      conductance. A biphasic time dependence for the activation of ionic currents was
      observed at low [Ca(2+)], which appeared to reflect the rapid activation of
      channels that were not blocked by Ca(2+) and a slower reversal of Ca(2+) blockade
      of the remaining channels. Removal of Ca(2+) following inactivation of Ca(2+)
      currents showed that Na(+) currents were not affected by Ca(2+)-dependent
      inactivation. Ca(2+)-dependent inactivation also induced a negative shift of the
      reversal potential for ionic currents suggesting that inactivation alters channel
      selectivity. Our findings suggest that activation of Ca(2+) conductance and
      Ca(2+)-dependent inactivation depend on extracellular Ca(2+) and are linked to
      changes in selectivity.

PMID- 15845582
TI  - Mitochondrial redox state and Ca2+ sparks in permeabilized mammalian skeletal
      muscle.
AB  - Intact skeletal muscle fibres from adult mammals exhibit neither spontaneous nor
      stimulated Ca(2+) sparks. Mechanical or chemical skinning procedures have been
      reported to unmask sparks. The present study investigates the mechanisms that
      determine the development of Ca(2+) spark activity in permeabilized fibres
      dissected from muscles with different metabolic capacity. Spontaneous Ca(2+)
      sparks were detected with fluo-3 and single photon confocal microscopy;
      mitochondrial redox potential was evaluated from mitochondrial NADH signals
      recorded with two-photon confocal microscopy, and Ca(2+) load of the sarcoplasmic
      reticulum (SR) was estimated from the amplitude of caffeine-induced Ca(2+)
      transients recorded with fura-2 and digital photometry. In three fibre types
      studied, there was a time lag between permeabilization and spark development.
      Under all experimental conditions, the delay was the longest in slow-twitch
      oxidative fibres, intermediate in fast-twitch glycolytic-oxidative fibres, and
      the shortest in fast-twitch glycolytic cells. The temporal evolution of Ca(2+)
      spark frequencies was bell-shaped, and the maximal spark frequency was reached
      slowly in mitochondria-rich oxidative cells but quickly in mitochondria-poor
      glycolytic fibres. The development of spontaneous Ca(2+) sparks did not correlate
      with the SR Ca(2+) content of the fibre, but did correlate with the redox
      potential of their mitochondria. Treatment of fibres with scavengers of reactive
      oxygen species (ROS), such as superoxide dismutase (SOD) and catalase,
      dramatically and reversibly reduced the spark frequency and also delayed their
      appearance. In contrast, incubation of fibres with 50 microm H(2)O(2) sped up the
      development of Ca(2+) sparks and increased their frequency. These results
      indicate that the appearance of Ca(2+) sparks in permeabilized skeletal muscle
      cells depends on the fibre's oxidative strength and that misbalance between
      mitochondrial ROS production and the fibre's ability to fight oxidative stress is
      likely to be responsible for unmasking Ca(2+) sparks in skinned preparations.
      They also suggest that under physiological and pathophysiological conditions the
      appearance of Ca(2+) sparks may be, at least in part, limited by the fine-tuned
      equilibrium between mitochondrial ROS production and cellular ROS scavenging
      mechanisms.

PMID- 15845583
TI  - ATP contributes to the generation of network-driven giant depolarizing potentials
      in the neonatal rat hippocampus.
AB  - In the immature hippocampus, the so-called 'giant depolarizing potentials' (GDPs)
      are network-driven synaptic events generated by the synergistic action of
      glutamate and GABA. Here we tested the hypothesis that ATP, a widely distributed
      neurotransmitter, directly contributes to the network activity during the first
      postnatal week. We found that in CA3 pyramidal cells, in the presence of the
      adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), ATP produced a
      transient facilitation of GDPs followed by a depressant effect. A similar
      biphasic effect was produced by blockade of the ectoATPase activity with 6-N,N
      diethyl-D-beta,gamma-dibromomethylene ATP (ARL-67156). The effects of exogenous
      and endogenous ATP on GDPs were prevented by the P2X receptor antagonist
      pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). On pyramidal
      cells, ATP upregulated spontaneous action-potential-dependent GABA(A)-mediated
      synaptic events (GABA-SPSPs), suggesting a network-driven effect. Recordings from
      interneurones allowed comparison of ATP effects on GABAergic and glutamatergic
      synaptic activity. While ATP depressed GABA-SPSPs via metabotropic P2Y(1)
      receptors, it up- and downregulated glutamatergic SPSPs via PPADS-sensitive
      receptors. Thus, ATP exerts an excitatory action on CA3 pyramidal cells via
      facilitation of GDPs and SPSPs. This excitatory drive is propagated to pyramidal
      cells by interneurons that represent the 'common pathway' for generation of GDPs
      and SPSPs. Our results show that ATP operating via distinct P2X and P2Y receptors
      directly contributes to modulate network activity at the early stages of
      postnatal development.

PMID- 15845584
TI  - Timing-dependent plasticity in human primary somatosensory cortex.
AB  - Animal experiments suggest that cortical sensory representations may be
      remodelled as a consequence of changing synaptic efficacy by timing-dependent
      associative neuronal activity. Here we describe a timing-based associative form
      of plasticity in human somatosensory cortex. Paired associative stimulation (PAS)
      was performed by combining repetitive median nerve stimulation with transcranial
      magnetic stimulation (TMS) over the contralateral postcentral region. PAS
      increased exclusively the amplitude of the P25 component of the median nerve
      evoked somatosensory-evoked potential (MN-SSEP), which is probably generated in
      the superficial cortical layers of area 3b. SSEP components reflecting neuronal
      activity in deeper cortical layers (N20 component) or subcortical regions (P14
      component) remained constant. PAS-induced enhancement of P25 amplitude displayed
      topographical specificity both for the recording (MN-SSEP versus tibial nerve
      SSEP) and the stimulation (magnetic stimulation targeting somatosensory versus
      motor cortex) arrangements. Modulation of P25 amplitude was confined to a narrow
      range of interstimulus intervals (ISIs) between the MN pulse and the TMS pulse,
      and the sign of the modulation changed with ISIs differing by only 15 ms. The
      function describing the ISI dependence of PAS effects on somatosensory cortex
      resembled one previously observed in motor cortex, shifted by approximately 7 ms.
      The findings suggest a simple model of modulation of excitability in human
      primary somatosensory cortex, possibly by mechanisms related to the spike-timing
      dependent plasticity of neuronal synapses located in upper cortical layers.

PMID- 15845585
TI  - Functional evidence for cone-specific connectivity in the human retina.
AB  - Physiological studies of colour vision have not yet resolved the controversial
      issue of how chromatic opponency is constructed at a neuronal level. Two
      competing theories, the cone-selective hypothesis and the random-wiring
      hypothesis, are currently equivocal to the architecture of the primate retina. In
      central vision, both schemes are capable of producing colour opponency due to the
      fact that receptive field centres receive input from a single bipolar cell - the
      so called 'private line arrangement'. However, in peripheral vision this single
      cone input to the receptive field centre is lost, so that any random cone
      connectivity would result in a predictable reduction in the quality of colour
      vision. Behavioural studies thus far have indeed suggested a selective loss of
      chromatic sensitivity in peripheral vision. We investigated chromatic sensitivity
      as a function of eccentricity for the cardinal chromatic (L/M and S/(L + M)) and
      achromatic (L + M) pathways, adopting stimulus size as the critical variable.
      Results show that performance can be equated across the visual field simply by a
      change of scale (size). In other words, there exists no qualitative loss of
      chromatic sensitivity across the visual field. Critically, however, the
      quantitative nature of size dependency for each of the cardinal chromatic and
      achromatic mechanisms is very specific, reinforcing their independence in terms
      of anatomy and genetics. Our data provide clear evidence for a physiological
      model of primate colour vision that retains chromatic quality in peripheral
      vision, thus supporting the cone-selective hypothesis.

PMID- 15845586
TI  - Navigation in space--the role of the macaque ventral intraparietal area.
AB  - Goal-directed self-motion through space is anything but a trivial task. What we
      take for granted in everyday life requires the complex interplay of different
      sensory and motor systems. On the sensory side most importantly a target of
      interest has to be localized relative to one's own position in space. On the
      motor side the most critical step in neural processing is to define and perform a
      movement towards the target as well as the avoidance of obstacles. Furthermore,
      the multisensory (visual, tactile and auditory) motion signals as induced by
      one's own movement have to be identified and differentiated from the real motion
      of visual, tactile or auditory objects in the outside world. In a number of
      experimental studies performed in recent years we and others have functionally
      characterized a subregion within monkey posterior parietal cortex (PPC) that
      appears to be well suited to contribute to such multisensory encoding of spatial
      and motion information. In this review I will summarize the most important
      experimental findings on the functional properties of this very region in monkey
      PPC, i.e. the ventral intraparietal area.

PMID- 15845587
TI  - Time and intensity coding at the hair cell's ribbon synapse.
AB  - The activity of individual afferent neurones in the mammalian cochlea can be
      driven by neurotransmitter released from a single synaptic ribbon in a single
      inner hair cell. Thus, a ribbon synapse must be able to transmit all the
      information on sound frequency, intensity and timing carried centrally. This task
      is made still more demanding by the process of binaural sound localization that
      utilizes separate computations of time and intensity, with temporal resolution as
      fine as 10 micros in central nuclei. These computations may rely in part on the
      fact that the response phase (at the characteristic frequency) of individual
      afferent neurones is invariant with intensity. Somehow, the ribbon synapse can
      provide stronger synaptic drive to signal varying intensity, without accompanying
      changes in transmission time that ordinarily occur during chemical
      neurotransmission. Recent ultrastructural and functional studies suggest features
      of the ribbon that may underlie these capabilities.

PMID- 15845588
TI  - Age is no barrier to muscle structural, biochemical and angiogenic adaptations to
      training up to 24 months in female rats.
AB  - Ageing is associated with reduced transport and utilization of O(2), diminishing
      exercise tolerance. Reductions may occur in cardiac output (delivery), and
      skeletal muscle oxidative capacity (utilization). To determine the reversibility
      of the declines in the muscular determinants of these limitations, skeletal
      muscle morphological, angiogenic and biochemical responses to acute exercise and
      endurance training were investigated in female Fischer 344 rats (n = 42; seven
      groups of six rats) aged 6 (Y) and 24 (O) months compared with resting untrained
      controls (Y(C), O(C)). Treadmill training lasted 8 weeks (10 deg incline, 1 h per
      day, 5 days per week). Two groups ran at maximum tolerated speeds (Y(TR), O(TR)),
      while an additional Y group (Y(TM)) trained at O(TR) speed. There was no effect
      of age on vascular endothelial growth factor gene expression in gastrocnemius
      muscles after acute exercise. Similarly, age did not impair the effects of
      training, with increases (P < 0.05; +/-s.e.m.) occurring in all of the following:
      1 h exercise running speed (Y(TR) 92 +/- 4% versus O(TR) 140 +/- 25%); citrate
      synthase (Y(TR) 37 +/- 8% versus O(TR) 97 +/- 33%) and beta-hydroxyacyl-CoA
      dehydrogenase (Y(TR) 31 +/- 7%, versus O(TR) 72 +/- 24%) activities; and
      capillary-to-fibre ratio (Y(TR) 5.2 +/- 0.2% versus O(TR) 8.1 +/- 0.2%). However,
      Y(TM) muscle was unchanged in each measure compared with Y(C). In conclusion,
      these muscular responses to training were (1) not reduced by ageing, but (2)
      dependent on relative and not absolute work rate, since, at the same speed, O(TR)
      rats showed greater changes than Y(TM). Therefore, increases in exercise
      tolerance and muscle adaptations are not impaired in female rats up to 24 months
      of age, and require a smaller absolute exercise stimulus (than young) to be
      manifest.

PMID- 15845589
TI  - A critical role of TRPM channel-kinase for human magnesium transport.
AB  - Hereditary disorders of magnesium homeostasis comprise a heterogenous group of
      diseases mainly affecting the renal conservation of magnesium. In the past few
      years, genetic studies in affected individuals disclosed the first molecular
      components of epithelial magnesium transport: the tight junction protein
      paracellin-1 (claudin-16) was discovered as a key player in paracellular
      magnesium and calcium reabsorption in the thick ascending limb of Henle's loop
      and the gamma-subunit was identified as a component of renal Na+ -K+ -ATPase
      critical for transcellular magnesium reabsorption in the distal convoluted
      tubule. However, the molecular identity of proteins directly involved in cellular
      magnesium transport remained largely unknown until a series of recent studies
      highlighted the critical role of two members of the transient receptor potential
      (TRP) family, for body magnesium homeostasis. TRPM6 and TRPM7 belong to the
      melastatin-related TRPM subfamily of TRP channels whose eight members exhibit a
      significant diversity in domain structure as well as cation selectivity and
      activation mechanisms. Both proteins share the unique feature of an atypical
      kinase domain at their C-terminus for which they have been termed 'chanzymes'
      (channels plus enzymes). Whereas electrophysiological and biochemical analyses
      identified TRPM7 as an important player in cellular magnesium homeostasis, the
      critical role of TRPM6 for epithelial magnesium transport emerged from the
      discovery of loss-of-function mutations in patients with a severe form of
      hereditary hypomagnesaemia called primary hypomagnesaemia with secondary
      hypocalcaemia or HSH. The aim of this review is to summarize the data emerging
      from molecular genetic, biochemical and electrophysiological studies on these
      fascinating two new proteins combining ion channel and enzyme
      functions/properties.

PMID- 15845590
TI  - Transcripts from a human primordial follicle cDNA library.
AB  - BACKGROUND: Human primordial follicles (PFs) or the oocyte-pre-granulosa complex,
      constitute the earliest and most immature stage of human oogenesis. The factors,
      signalling networks and the precise role of the oocyte and the pre-granulosa
      cells in initiating growth and recruitment from this finite resting pool remain
      largely unknown at present. METHODS: To obtain a gene resource of this oogenesis
      stage and thereby determine a molecular blueprint of the human PF, a cDNA library
      was constructed from 50 isolated human PFs using the phagemid vector pTriplEx2.
      RESULTS: Sequence analysis showed that 46.67% of these clones corresponded to
      known genes while 29.48% were uncharacterized genes that included hypothetical
      proteins, human cDNA clones and novel genes. Bioinformatics analysis revealed a
      preponderance of mitochondrial genes and repeat elements followed by ribosomal
      proteins, transcription and translation genes. Transcripts for heat shock
      proteins, cell cycle, embryogenesis genes and apoptosis genes were identified.
      Members of the ubiquitin-proteasome pathway, MAPK, p38/JNK, GPCR, Wnt, NF-kappaB
      and notch signalling pathways were identified. A mitochondrial pathway and a
      transcription factor pathway in the human PF were generated. The gene networks in
      the transcription factor pathway provided a first glimpse of the balance between
      proliferation and cell death/apoptosis in this earliest stage of oogenesis.
      CONCLUSIONS: The abundance and diversity of retroviral elements and
      transcriptional repressor genes in the human PF suggest these could contribute to
      the maintainance of this oogenesis stage. The role of these genes in initial
      recruitment and in subsequent oogenesis stages will be greatly facilitated and
      elucidated by printing a human PF cDNA array of the sequenced clones and using it
      for gene profiling.

PMID- 15845591
TI  - Gonadotrophin therapy in Kallmann syndrome caused by heterozygous mutations of
      the gene for fibroblast growth factor receptor 1: report of three families: case
      report.
AB  - Gonadotrophin therapy (GT) is frequently used to induce fertility in Kallmann
      syndrome (KS). We studied the effects and the consequences of GT in autosomal
      dominant KS caused by heterozygous FGFR1 mutations. Three Japanese families were
      examined. In family A, an adult male received GT and had two sons. In family B,
      an adult female received GT and gave birth to dizygotic male and female twins. In
      family C, an adult female received GT and produced a son and a daughter. Direct
      sequencing was performed for FGFR1, and clinical assessment was carried out for
      KS features. The father and the elder son of family A had P745S mutation, the
      mother and the female twin of family B had G687R mutation, and the mother and the
      two children of family C had S107X mutation. KS phenotype was detected for the
      mutation-positive subjects, except for the elder son of family A who had
      apparently normal phenotype. GT in FGFR1 mutations is effective in acquiring
      fertility but has a risk of transmitting the mutation and the disease phenotype
      to the next generation.

PMID- 15845592
TI  - The safety of ultrasonically guided testis aspiration biopsies and efficacy of
      use to predict varicocelectomy outcome.
AB  - BACKGROUND: We hypothesized that infertile men with varicoceles have
      molecular/genetic defects that interact with varicoceles to induce infertility.
      Studies directly on testis tissue appeared to be a way to link histology, markers
      for molecular/genetic defects and spermatogenesis, but testis biopsies may induce
      morbidity. In this report, we present safety and efficacy data on ultrasonically
      guided, single stick, percutaneous aspiration. METHODS: Biopsies were performed
      on 115 infertile men with varicoceles and five men with obstructive azoospermia.
      Morbidity was examined by pre- and post-biopsy ultrasound, efficacy by ability of
      two markers to predict >50% increase in sperm density post-operatively. All
      patients had three pre- and three post-operative semen analyses. RESULTS: 78.3%
      of patients had no ultrasonic testicular defects immediately post-biopsy. By 2
      months, 100% had no defects. Biopsy markers [testicular cadmium (<0.453 ng/mg
      tissue) and an intact calcium channel mRNA sequence] predicted >50% increase in
      sperm density with 82.9 and 90.5% accuracy, respectively. CONCLUSIONS:
      Ultrasonically controlled, percutaneous aspiration testis biopsies are safe.
      Specimens so acquired can assist study of molecular/genetic markers associated
      with spermatogenesis in infertile men with varicoceles. Tissue cadmium level,
      calcium channel sequence and other markers may predict outcome of varicocele
      surgery.

PMID- 15845593
TI  - Cytogenetic, molecular and testicular tissue studies in an infertile 45,X male
      carrying an unbalanced (Y;22) translocation: case report.
AB  - (Y;autosome) translocations have been reported in association with male
      infertility. Different mechanisms have been suggested to explain the male
      infertility, such as deletion of the azoospermic factor (AZF) on the long arm of
      the Y chromosome, or meiosis impairment. We describe a new case with a de novo
      unbalanced translocation t(Y;22) and discuss the genotype-phenotype correlation.
      A 36 year old male with azoospermia was found to have a mosaic 45,X/46,X, + mar
      karyotype. Fluorescence in situ hybridization (FISH) showed the presence of a
      derivative Y chromosome containing the short arm, the centromere and a small
      proximal part of the long-arm euchromatin of the Y chromosome and the long arm of
      chromosome 22. The unstable small marker chromosome included the short arm and
      the centromere of chromosome 22. This unbalanced translocation
      t(Y;22)(q11.2;q11.1) generated the loss of the long arm of the Y chromosome
      involving a large part of AZFb, AZFc and Yq heterochromatin regions. Testicular
      tissue analyses showed sperm in the wet preparation. Our case shows the
      importance of documenting (Y;autosome) translocations with molecular and
      testicular tissue analyses.

PMID- 15845594
TI  - Frequency of aneuploidy in sperm from patients with extremely severe male factor
      infertility.
AB  - BACKGROUND: A protocol for the chromosomal analysis of sperm samples with a
      severely reduced number of sperm cells was designed. METHODS: A severe male
      factor condition was the main cause of infertility for 38 couples: 27 were
      oligoasthenoteratospermic (OAT) and 11 with non-obstructive azoospermia underwent
      testicular sperm extraction (TESE). A two-round fluorescence in situ
      hybridization (FISH) protocol was performed with probes specific for the
      chromosomes X, Y, 13, 15, 16, 17, 18, 21 and 22. The recording of the position of
      each sperm cell at the microscope allowed diagnosis of each spermatozoon for the
      nine tested chromosomes. RESULTS: A mean number of 122+/-78.5 sperm were
      diagnosed per patient with an incidence of total abnormalities corresponding to
      13.4%. chi2-tests for the observed frequencies and goodness-of-fit test were
      highly significant in all cases. A significantly higher proportion of total
      aneuploidy was detected in 79% of the tested samples compared to the normal
      population. Testicular sperm were significantly more prone to aneuploidy than
      ejaculated sperm. CONCLUSIONS: The designed FISH protocol for the analysis of
      severe OAT and TESE sperm samples is reliable, implying that the studied sample
      is representative of the original population. In view of the high incidence of
      aneuploidy in most severe OAT and TESE sperm, the FISH analysis of pathological
      sperm samples can be routinely performed in order to estimate the chances of the
      paternal contribution to aneuploidy in the resulting embryos.

PMID- 15845595
TI  - Expression of inhibin alpha, glial cell line-derived neurotrophic factor and stem
      cell factor in Sertoli cell-only syndrome: relation to successful sperm retrieval
      by microdissection testicular sperm extraction.
AB  - BACKGROUND: Microdissection testicular sperm extraction (TESE) has provided new
      hope for successful sperm retrieval to patients with Sertoli cell-only syndrome
      (SCO). We determined expression of the inhibin alpha subunit, glial cell line
      derived neurotrophic factor (GDNF) and stem cell factor (SCF) in Sertoli cells
      obtained from patients with SCO immunohistochemically and compared expression
      rates with rates of microdissection TESE sperm retrieval. METHODS: Testicular
      biopsy specimens were obtained from 52 men with non-obstructive azoospermia who
      underwent microdissection TESE and were diagnosed with SCO by histological
      analysis. RESULTS: All specimens showed intense staining for the inhibin alpha
      subunit. Moderate or intense staining for GDNF was observed in 65.8% of
      specimens. All but one showed moderate or intense staining for SCF. Among
      specimens negative for GDNF, the sperm retrieval rate was significantly higher
      (100%) for specimens with intense staining for SCF than for specimens with no or
      moderate staining (30.7%) (P<0.05) for SCF. CONCLUSION: GDNF expression differs
      among patients with SCO. The sperm retrieval rate was high in cases of no
      staining for GDNF and intense staining for SCF.

PMID- 15845596
TI  - Is quality assurance in semen analysis still really necessary? A clinician's
      viewpoint.
AB  - Quality assurance in semen analysis is now a standard procedure in most andrology
      laboratories. This communication is now questioning its value in any clinical
      situation and as a consequence asks whether the effort and the expense of such a
      process is really worthwhile. It concludes that semen analysis needs only to be
      performed competently without the need for costly and time-consuming forms of
      quality assurance.

PMID- 15845597
TI  - Sperm segregation analysis of a (13;22) Robertsonian translocation carrier by
      FISH: a comparison of locus-specific probe and whole chromosome painting.
AB  - BACKGROUND: The t(13;22) Robertsonian translocation constitutes a rare form of
      rearrangement between acrocentric human chromosomes. Most of the meiotic
      segregation studies of human Robertsonian translocations have been performed on
      common t(13;14) and t(14;21) translocations. Analysis of the chromosomal
      constitution in sperm of Robertsonian translocation carriers is of great interest
      for assessing the risk of unbalanced forms and adapting genetic counselling. In
      the present study, we present the first meiotic segregation study of a t(13;22)
      Robertsonian translocation in human sperm. METHODS: A total of 11 787 sperm
      nuclei were scored using two distinct FISH labelling techniques, i.e. the locus
      specific probes (LSI) method and the whole chromosome painting (WCP) technique.
      RESULTS: The frequency of normal or balanced sperm resulting from alternate
      meiotic segregation was 86%. Incidences of unbalanced complements resulting from
      adjacent segregation modes were 12.79% and 14.36% in LSI and WCP assays,
      respectively. No significant excess of nullisomy or disomy for the affected
      chromosomes was observed. CONCLUSIONS: Similar results in segregation were
      obtained with the two techniques, demonstrating the efficiency of the two
      strategies for the direct segregation analysis of Roberstsonian translocations.
      The results obtained indicated a moderate meiotic production of imbalance. This
      study shows that the rare Robertsonian translocation (13;22) displays a similar
      distribution of balanced and unbalanced sperm patterns as the common Robertsonian
      translocations previously studied. This suggests that the behaviour of
      acrocentric chromosomes was similar in all cases of centric fusion.

PMID- 15845598
TI  - Comparison of ovarian stromal blood flow between fertile women with normal
      ovaries and infertile women with polycystic ovary syndrome.
AB  - BACKGROUND: Conflicting information exists in the literature with respect to
      ovarian stromal blood flow in women with polycystic ovary syndrome (PCOS). We
      compared the ovarian stromal blood flow and serum vascular endothelial growth
      factor (VEGF) concentration between fertile women with normal ovaries and
      infertile women with PCOS. METHODS: In the second to fourth day of the menstrual
      period, they underwent transvaginal scanning with three-dimensional (3D) power
      Doppler to determine total antral follicle count (AFC), total ovarian volume,
      total ovarian vascularization index (VI), flow index (VFI) and vascularization
      flow index (VFI). Serum FSH, LH and VEGF concentrations were also checked.
      RESULTS: 107 fertile controls and 32 PCOS women were recruited. Fertile controls
      and PCOS women had similar total ovarian VI/FI/VFI after controlling for age of
      the woman, although PCOS women had significantly higher total AFC, total ovarian
      volume and serum LH concentration than fertile controls. Total ovarian VI/FI/VFI
      were significantly higher in normal weight (BMI < 25 kg/m2) PCOS women than their
      overweight (> or = 25 kg/m2) counterparts. CONCLUSIONS: Fertile controls and PCOS
      women had similar total ovarian 3D power Doppler flow indices. Normal weight PCOS
      women had significantly higher total ovarian 3D power Doppler flow indices than
      their overweight counterparts.

PMID- 15845599
TI  - Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta
      analysis.
AB  - BACKGROUND: Both selective estrogen receptor modulators, tamoxifen and clomiphene
      have been used for ovulation induction for patients with anovulatory infertility.
      This meta-analysis sought to compare the effectiveness of tamoxifen to clomiphene
      for the induction of ovulation and achievement of pregnancy. METHODS: We searched
      MEDLINE, BIOSIS, PreMEDLINE, CINAHL, International Pharmaceutical Abstracts,
      DDSR, ACP Journal Club, DARE and CCTR, along with reference lists and national
      experts. Inclusion criteria were prospective clinical trials, which compared
      tamoxifen and clomiphene for ovulation induction in infertile couples with
      isolated anovulatory infertility. Main outcome measures were ovulation rate and
      clinical pregnancy rate. Pooled odds ratios were obtained using random effects
      meta-analysis. RESULTS: Four trials were included. After pooling all the trials,
      the use of tamoxifen or clomiphene citrate resulted in similar ovulation rates
      [odds ratio (OR) 0.755, 95% confidence interval (CI) 0.513-1.111]. There was no
      benefit of tamoxifen over clomiphene citrate in achievement of pregnancy per
      cycle (OR 1.056, 95% CI 0.583-1.912) or per ovulatory cycle (OR 1.162, 95% CI
      0.632-2.134). CONCLUSIONS: Clomiphene citrate and tamoxifen are equally effective
      in inducing ovulation. Although data regarding pregnancy rates and outcome are
      limited, there does not appear to be a significant benefit of one medication over
      the other.

PMID- 15845600
TI  - The relationship between mammographic density and duration of hormone therapy:
      effects of estrogen and estrogen-progestin.
AB  - BACKGROUND: The purpose of this study was to examine the effects of duration of
      hormone therapy (HT) and treatment regimens on mammographic density. METHODS: A
      retrospective study was carried out of of 467 post-menopausal women who received
      estrogen or estrogen-progestin and had regular mammographic density determination
      by the Breast Imaging Reporting and Data System between 1994 and 2001. RESULTS:
      The fraction of women using HT who had an increase in mammographic density became
      more important over time. Further analysis of the effects of regimens after 4
      years of HT shows that the increase in mean density was much greater in women
      receiving combined HT than in those receiving estrogen alone. The incidence of
      increased mammographic density showed significantly progressive increases over
      the duration of combined HT from 7.5 to 22.4%. CONCLUSIONS: Although most women
      using HT maintained breast density at pre-treatment levels, there is a note of
      caution for women using long-term HT, especially those using combined estrogen
      progestin.

PMID- 15845601
TI  - Post-coital administration of levonorgestrel and post-fertilization events in the
      new-world monkey Cebus apella.

PMID- 15845602
TI  - Assisted hatching improves implantation rates on cryopreserved-thawed embryos. A
      randomized prospective study.

PMID- 15845603
TI  - Ethics of assisted reproduction for HIV concordant couples.

PMID- 15845604
TI  - Proposal to adapt the Workplace Analysis Scheme for Proficiency (WASP) programme
      to fibre counting tests.
AB  - Three methods of classifying laboratories during fibre counting proficiency tests
      were compared. The first two are those used in France (classification according
      to the mean and coefficient of variation of the results) and in Great Britain
      (classification according to the proportion of normalized results situated within
      predefined limits). The third is a variation of the Workplace Analysis Scheme for
      Proficiency (WASP) programme adapted to fibre counting tests. In the latter case,
      the laboratory classification is based on comparing the variance characterizing
      the dispersion of the results of a laboratory with a reference variance, which is
      considered as the variance of experienced analysts or laboratories. This mode of
      processing has the advantage of allowing the comparison of magnitudes. For
      example, the variance of the reference value can be compared with the reference
      variance. The same applies if a proficiency test is organized on the basis of
      replicas distributed to different analysts, the variability of these replicas can
      be compared with the reference variance. It emerged that the modified WASP method
      produces results close to those obtained by the other two methods. Moreover, the
      selectivity of the three methods is evaluated.

PMID- 15845605
TI  - Metalworking fluids--clearing away the mist?

PMID- 15845606
TI  - Investigation of determinants of past and current exposures to formaldehyde in
      the reconstituted wood panel industry in Quebec.
AB  - OBJECTIVES: Past and present formaldehyde measurements made in facilities
      manufacturing reconstituted wood panels in Quebec have been collected in order to
      assess formaldehyde exposure and its determinants in this industry. METHODS: All
      12 plants manufacturing Oriented-strand board (OSB), Medium density fibreboard
      (MDF) and Particle board (PB) in Quebec were visited by a research team which
      took area and personal measurements. Past measurements taken by governmental
      occupational health teams in these plants were also collected. Log-transformed
      formaldehyde concentrations were analysed with extended linear mixed-effects
      models. RESULTS: During 2001-2002, 275 measurements were taken by the research
      team, while 590 measurements dating back to 1984 were collected from governmental
      files. The area measurements had a global geometric mean (GM) of 0.28 p.p.m.
      [geometric standard deviation (GSD): 3.1]. The GM of the personal measurements
      was 0.17 p.p.m. (GSD: 2.3). The fixed-effects of the models for personal and area
      measurements explained 61 and 57% of the variance, respectively. Job (working
      area for area concentrations), process (PB, MDF, OSB), season of sampling, origin
      of the data (research, governmental) and year of sampling were significant
      determinants of exposure. Proximity to the press, winter conditions, PB and MDF
      processes and governmental data resulted in the highest exposures. Significant
      within-sampling campaign correlation was found for both personal and area models.
      The final models include different residual variances by process for personal
      measurements and by working area for area measurements. CONCLUSIONS: Several
      determinants of exposure to formaldehyde in the reconstituted wood panel industry
      were successfully identified. Higher levels found in governmental data as
      compared to research data may be explained by a 'worst-case' strategy bias. The
      observed intra-sampling campaign correlation supports existing results suggesting
      that measurements taken in a small time frame tend to be correlated. Exposures in
      this sector are low compared to most 8 h-TWA occupational exposure limits (e.g. 1
      p.p.m.) but close to the most demanding ones (e.g. 0.3 p.p.m.).

PMID- 15845607
TI  - Variability in dust exposure in a cement factory in Tanzania.
AB  - Dust exposure levels were studied in a cement factory in Dar es Salaam, Tanzania,
      as part of an epidemiological study assessing chronic respiratory health effects.
      One hundred and twenty personal 'total' dust samples were collected from 80
      randomly selected workers from eight a priori occupational groups (OGs) based on
      work areas using a 37 mm Millipore sampler. The between-group, within-group and
      within-worker variances were determined to assess the contrast in exposure level
      between the OGs and to estimate the attenuation and standard error of the
      theoretical exposure-response slope. Using mixed-effect model estimates, the
      probability of overexposure relative to the occupational exposure limit (OEL) was
      assessed for each OG. The geometric means of total dust exposure were higher in
      the cranes (38.64 mg m(-3)), packing (21.30 mg m(-3)) and crusher (13.48 mg m(
      3)) than in the cement mill (3.23 mg m(-3)), kiln (2.87 mg m(-3)), raw mill (1.85
      mg m(-3)), maintenance (1.16 mg m(-3)) and administration (0.29 mg m(-3)). The a
      priori grouping scheme seems to be an efficient scheme because of the high
      contrast in exposure level between the OGs (0.78) and minimal attenuation of the
      theoretical exposure-response slope (1.0%). When using the reduced mixed-effect
      model, the probabilities of overexposure () relative to the OEL of 10 mg m(-3)
      for total cement dust were higher in the crane (96%), packing (88%) and crusher
      (73%) than in the cement mill (16%), kiln (14%), raw mill (5%), maintenance (2%)
      and administration (0.01%).

PMID- 15845608
TI  - Evaluation of misting controls to reduce respirable silica exposure for brick
      cutting.
AB  - It is estimated that more than 1.7 million workers in the United States are
      potentially exposed to respirable crystalline silica, with a large percentage
      having been exposed to silica concentrations higher than the limits set by
      current standards and regulations. The purpose of this study is to characterize
      the use of water-misting engineering controls to reduce exposure to respirable
      crystalline silica for construction workers engaged in the task of brick cutting.
      Since data concerning the efficacy of engineering controls collected at worksites
      is often confounded by factors such as wind, worker skill level, the experiments
      were conducted in a laboratory environment. A completely enclosed testing chamber
      housed the brick-cutting saw. Respirable dust concentrations were measured using
      the Model 3321 Aerodynamic Particle Sizer. Specifically, the laboratory
      experiment was designed to compare dust suppression through water misting using
      conventional freely flowing water techniques. Brass atomizing nozzles with three
      flow rates were used for making this comparison: low (5.0 ml s(-1) or 4.8 gal h(
      1)), medium (9.0 ml s(-1) or 8.6 gal h(-1)) and high (18 ml s(-1) or 17.3 gal h(
      1)). The flow rate for freely flowing water, using manufacturer-supplied
      equipment, was 50 ml s(-1) (48 gal h(-1)). The experiment consisted of five
      replications of five samples each (low-misting, medium-misting, high-misting,
      freely flowing water and no control). The order of sampling within each replicate
      was randomized. Estimates of dust reduction showed that low-misting nozzles
      reduced the respirable mass fraction of dust by about 63%, medium-misting nozzles
      by about 67%, high-misting nozzles by about 79% and freely flowing water by about
      93%. Based on these results, it may be feasible to use misting to control
      respirable silica dust instead of freely flowing water. This strategy is of
      practical interest to the construction industry which must frequently limit the
      amount of water used on construction sites.

PMID- 15845609
TI  - MPP+-induced COX-2 activation and subsequent dopaminergic neurodegeneration.
AB  - The importance of cyclooxygenase-2 (COX-2) in mediating Parkinson's disease (PD)
      was suggested in reports, indicating that COX-2 selective inhibitors or genetic
      knockout reduce 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
      dopaminergic (DA) neurotoxicity in a mouse model of PD. However, cell types and
      mechanisms underlying the activation of COX-2 have not been clearly elucidated in
      these animal studies. Using primary neuron-glia cultures, we aimed to determine
      1) whether microglia participate in 1-methyl-4-phenylpryridinium (MPP)-induced
      COX-2 activation and 2) whether the activation of COX-2 contributes to subsequent
      neurotoxicity. MPP, in a concentration-dependent manner, increased prostaglandin
      E2 (PGE2) production in mixed neuron-microglia cultures but not in enriched
      neuron, microglia, or astroglia cultures nor in mixed neuron-astroglia cultures.
      MPP-induced PGE2 increase was completely abolished by treatment with DuP697, a
      COX-2 selective inhibitor. DuP697 also significantly reduced MPP-induced DA
      neurotoxicity as determined by DA uptake assay. Immunocytochemistry and confocal
      microscopy studies showed enhanced COX-2 expression in both microglia and neurons
      after MPP treatment. However, neuronal increase in COX-2 expression was not
      totally dependent on the production of PGE2 from microglia, since microglia
      deficient in COX-2 only attenuated, but did not completely block, MPP-increased
      PGE2 production in mixed neuron-microglia cultures, suggesting that part of PGE2
      production was originated from neurons. Together, these results indicate that MPP
      induced COX-2 expression and subsequent PGE2 production depend on interactions
      between neurons and microglia. Microgliosis may also be responsible for the COX-2
      activation in neurons, leading to the enhanced DA neurotoxicity, which, in turn,
      reinforces microgliosis. Thus inhibition of microgliosis and COX-2 activity may
      stop this vicious circle and be valuable strategies in PD therapy.

PMID- 15845610
TI  - Selective cyclooxygenase (COX) inhibition causes damage to portal hypertensive
      gastric mucosa: roles of nitric oxide and NF-kappaB.
AB  - Portal hypertension (PHT) is associated with increased susceptibility of the
      gastric mucosa to injury by a variety of factors, including nonsteroidal anti
      inflammatory drugs (NSAIDs) that nonselectively inhibit both isoforms of
      cyclooxygenase (COX-1 and -2). PHT gastric mucosa also has excessive nitric oxide
      (NO) production that contributes to the general increased susceptibility to
      injury. Using a rat model of PHT, we studied whether selective COX inhibition,
      which does not damage normal (normotensive) gastric mucosa, is sufficient to
      cause PHT gastric damage and, if so, whether and how excessive NO is involved.
      Indomethacin, a nonselective NSAID, caused 2.4-fold more gastric injury to PHT
      vs. normotensive sham-operated (SO) control rats. Neither NS-398 nor celecoxib,
      selective COX-2 inhibitors, caused gastric damage in either SO or PHT rats. SC
      560, a selective COX-1 inhibitor, did not cause gastric damage in SO rats but
      dose-dependently caused gastric damage in PHT rats. There was a compensatory
      increase in COX-2 expression and activity in SC-560-treated SO rats but not SC
      560-treated PHT rats. Partial inhibition of NO production restored gastric COX-2
      expression and activity levels in SC-560-treated PHT rats to those of SC-560
      treated SO rats, by a mechanism consistent with induction of NF-kappaB, and
      significantly reduced gastric damage. These studies indicate that, in contrast to
      normotensive gastric mucosa, inhibition of COX-1 alone is sufficient to cause PHT
      gastric damage as a result of excessive NO that prevents the induction of NF
      kappaB and the compensatory increase in COX-2.

PMID- 15845611
TI  - Extracardiac vascular disease and effectiveness of sustained clopidogrel
      treatment.
AB  - OBJECTIVE: To assess the effectiveness of long term treatment with clopidogrel of
      patients with extracardiac vascular disease (ECVD) (a history of either
      peripheral arterial disease or cerebrovascular disease). DESIGN: Subgroup
      analysis of a prospective randomised clinical trial. SETTING: The CREDO
      (clopidogrel for the reduction of events during observation) trial was a
      randomised, double blind, placebo controlled trial conducted at 99 centres in
      North America from June 1999 through April 2001. PATIENTS: 2116 patients who were
      to undergo elective coronary intervention or were deemed at high likelihood of
      undergoing percutaneous coronary intervention were enrolled in the CREDO trial.
      The current study sample consisted of 272 patients with ECVD. MAIN OUTCOME
      MEASURE: One year incidence of the composite of death, myocardial infarction, or
      stroke in the intent to treat population. RESULTS: Patients with ECVD had a more
      than twofold greater relative risk reduction with clopidogrel for the primary end
      point compared with patients without ECVD (47.9%, 95% confidence interval (CI) 
      4.2% to 73.9%, v 18.2%, 95% CI -10.5 % to 39.5%, respectively). CONCLUSIONS:
      Longer term clopidogrel treatment provides added protection against thrombotic
      events throughout the arterial vasculature, not limited to the coronary arteries,
      and may be especially effective for patients with more diffuse atherosclerosis
      such as ECVD.

PMID- 15845612
TI  - Outcome after extended arch repair for aortic coarctation.
AB  - OBJECTIVES: To assess survival and long term arch patency rates in a consecutive
      group of children after extended arch repair for coarctation of the aorta.
      METHODS: Review of 191 consecutive children (154 (81%) under 1 year of age)
      operated on between 1990 and 2002 by a single surgeon using extended arch
      reconstructive techniques. For assessment of survival patients were divided into
      three groups: 1, coarctation alone, n = 104; 2, coarctation and ventricular
      septal defect, n = 38; and 3, coarctation in association with complex
      intracardiac anomalies, n = 49. A prospective and systematic clinical and
      echocardiographic evaluation of the aortic arch was undertaken. RESULTS: Median
      time to follow up was 4.2 years (range 1-10.6 years). Overall actuarial survival
      was 92%, 88%, and 88% at two, five, and 10 years. Mortality was significantly
      higher in those patients with complex intracardiac anatomy. Arch obstruction
      recurred in seven of 165 (4.2%) patients: four of 139 (2.9%) term and three of 10
      (30%) premature infants (p < 0.001). CONCLUSIONS: Survival after extended arch
      reconstruction for coarctation is excellent. At long follow up recurrent arch
      obstruction is rare, with prematurity the only risk factor.

PMID- 15845613
TI  - Assessment of coronary artery stents by 16 slice computed tomography.
AB  - OBJECTIVE: To analyse coronary stents with multislice spiral computed tomography
      (MSCT) in comparison with coronary angiography. PATIENTS AND METHODS: 310
      patients referred for conventional coronary angiography underwent MSCT on the
      next day (16 x 0.75 mm cross section, 420 ms rotation, 110 ml contrast agent
      intravenously at 4 ml/s). Two independent blinded reviewers analysed the MSCT.
      RESULTS: 143 patients had previous stenting (232 stents) and 190 (82%) of the 232
      stents were detected. Intrastent lumen was interpretable in 126 (64%) of the
      detected stents. Lumen interpretability depended on stent diameter: for stent
      diameter > 3 mm, 81% of lumens were interpretable, as against 51% with < or = 3
      mm stent diameter (p < 0.001). Restenosis detection likewise depended on stent
      diameter: with small stents (< or = 3 mm), sensitivity and specificity of MSCT
      were 54% and 100%, respectively; positive and negative predictive values were
      100% and 94%. For stents with > 3 mm diameter, corresponding values were 86%,
      100%, 100%, and 99%. CONCLUSION: 16 slice MSCT allows analysis of in-stent lumen
      in about half of all stented angioplasties. It performs better when stent
      diameter is more than 3 mm and may offer a non-invasive alternative to
      conventional coronary angiography for monitoring stented coronary arteries.
      Technical progress may improve interpretability and hence increase the yield of
      MSCT in this application.

PMID- 15845614
TI  - Heterozygous disruption of SERCA2a is not associated with impairment of cardiac
      performance in humans: implications for SERCA2a as a therapeutic target in heart
      failure.
AB  - OBJECTIVE: To verify whether a deficiency in the cardiac sarcoplasmic reticulum
      pump SERCA2a causes cardiac dysfunction in humans. DESIGN: Cardiac performance
      was measured in a serendipitous human model of primary SERCA2a deficiency,
      Darier's disease, an autosomal dominant skin disorder caused by mutations
      inactivating one copy of the ATP2A2 gene, which encodes SERCA2a. METHODS:
      Systolic and diastolic function and contractility were assessed by
      echocardiography at rest and during exercise in patients with Darier's disease
      with known mutations. Fourteen patients with Darier's disease were compared with
      14 normal controls and six patients with dilated cardiomyopathy with stable heart
      failure. RESULTS: Resting systolic and diastolic function was normal in patients
      with Darier's disease and in controls. The increase in systolic function during
      exercise was not different between patients with Darier's disease and normal
      controls; neither was there a difference in contractility. As expected, patients
      with dilated cardiomyopathy had impaired diastolic and systolic function with
      depressed contractility at rest and during exercise. CONCLUSION: Contrary to
      expectations, heterozygous disruption of SERCA2a is not associated with the
      impairment of cardiac performance in humans. Attempts to increase SERCA2a levels
      in heart failure, although showing promise in rodent studies, may not be
      addressing a critical causal pathway in humans.

PMID- 15845615
TI  - Proliferation of endothelial and tumor epithelial cells by progestin-induced
      vascular endothelial growth factor from human breast cancer cells: paracrine and
      autocrine effects.
AB  - Angiogenesis, the formation of new blood vessels, is essential for tumor
      expansion, and vascular endothelial growth factor (VEGF) is one of the most
      potent angiogenic growth factors known. We have previously shown that natural and
      synthetic progestins, including those used in hormone replacement therapy and
      oral contraception, induce the synthesis and secretion of VEGF in a subset of
      human breast cancer cells in a progesterone receptor-dependent manner. We now
      report that conditioned medium from progestin-treated breast tumor cells can
      induce the proliferation of endothelial cells in a paracrine manner and induce
      the proliferation of tumor epithelial cells in a paracrine and an autocrine
      manner. The use of an anti-VEGF antibody and SU-1498, an inhibitor of VEGF
      receptor-2 (VEGFR-2 or flk/kdr) tyrosine kinase activity, demonstrated that these
      effects involve interactions between VEGF and VEGFR-2. Also, blockage of
      progestin-induced VEGF by the antiprogestin RU-486 (mifepristone) eliminated VEGF
      induced proliferative effects. The ability of VEGF to increase the proliferation
      of endothelial cells and tumor cells, including those that do not release VEGF in
      response to progestins, suggests that these effects are mediated by amplification
      of the progestin signal, which culminates in angiogenesis and tumor growth. These
      novel findings suggest that targeting the release of VEGF from tumor epithelial
      cells as well as blocking interactions between VEGF and VEGFR-2 on both
      endothelial and tumor epithelial cells may facilitate the development of new
      antiangiogenic therapies for progestin-dependent breast tumors. Furthermore,
      these data indicate that it would be useful to develop selective progesterone
      receptor modulators that prevent the release of angiogenic growth factors from
      breast cancer cells.

PMID- 15845616
TI  - Identification of murine uterine genes regulated in a ligand-dependent manner by
      the progesterone receptor.
AB  - Progesterone (P4) acting through its cognate receptor, the progesterone receptor
      (PR), plays an important role in uterine physiology. The PR knockout (PRKO) mouse
      has demonstrated the importance of the P4-PR axis in the regulation of uterine
      function. To define the molecular pathways regulated by P4-PR in the mouse
      uterus, Affymetrix MG U74Av2 oligonucleotide arrays were used to identify
      alterations in gene expression after acute and chronic P4 treatments. PRKO and
      wild-type mice were ovariectomized and then treated with vehicle or 1 mg P4 every
      12 h. Mice were killed either 4 h after the first injection (acute P4 treatment)
      or after the fourth injection of P4 (chronic P4 treatment). At the genomic level,
      the major change in gene expression after acute P4 treatment was an increase in
      the expression of 55 genes. Conversely, the major change in gene expression after
      chronic P4 treatment was an overall reduction in the expression of 102 genes. In
      the analysis, retinoic acid metabolic genes, cytochrome P 450 26a1 (Cyp26a1),
      alcohol dehydrogenase 5, and aldehyde dehydrogenase 1a1 (Aldh1a1); kallikrein
      genes, Klk5 and Klk6; and specific transcription factors, GATA-2 and Cited2 [cAMP
      corticosterone-binding protein/p300-interacting transactivator with glutamic acid
      (E) and aspartic acid (D)-rich tail], were validated as regulated by the P4-PR
      axis. Identification and analysis of these responsive genes will help define the
      role of PR in regulating uterine biology.

PMID- 15845617
TI  - The inhibition of RANKL causes greater suppression of bone resorption and
      hypercalcemia compared with bisphosphonates in two models of humoral
      hypercalcemia of malignancy.
AB  - Humoral hypercalcemia of malignancy (HHM) is mediated primarily by skeletal and
      renal responses to tumor-derived PTHrP. PTHrP mobilizes calcium from bone by
      inducing the expression of receptor activator for nuclear factor-kappaB ligand
      (RANKL), a protein that is essential for osteoclast formation, activation, and
      survival. RANKL does not influence renal calcium reabsorption, so RANKL
      inhibition is a rational approach to selectively block, and thereby reveal, the
      relative contribution of bone calcium to HHM. We used the RANKL inhibitor
      osteoprotegerin (OPG) to evaluate the role of osteoclast-mediated hypercalcemia
      in two murine models of HHM. Hypercalcemia was induced either by sc inoculation
      of syngeneic colon (C-26) adenocarcinoma cells or by sc injection of high-dose
      recombinant PTHrP (0.5 mg/kg, s.c., twice per day). In both models, OPG (0.2-5
      mg/kg) caused rapid reversal of established hypercalcemia, and the speed and
      duration of hypercalcemia suppression were significantly greater with OPG (5
      mg/kg) than with high-dose bisphosphonates (pamidronate or zoledronic acid, 5
      mg/kg). OPG also caused greater reductions in osteoclast surface and biochemical
      markers of bone resorption compared with either bisphosphonate. In both models,
      hypercalcemia gradually returned despite clear evidence of ongoing suppression of
      bone resorption by OPG. These data demonstrate that osteoclasts and RANKL are
      important mediators of HHM, particularly in the early stages of the condition.
      Aggressive antiresorptive therapy with a RANKL inhibitor therefore might be a
      rational approach to controlling HHM.

PMID- 15845618
TI  - Temperature homeostasis in transgenic mice lacking thyroid hormone receptor-alpha
      gene products.
AB  - We studied temperature homeostasis in male mice lacking all thyroid hormone
      receptor-alpha gene products (TRalpha-0/0). As other TRalpha-deficient mice,
      TRalpha-0/0 mice have lower core body temperature (T(C)) than cognate wild-type
      controls. We found that obligatory thermogenesis is normal in TRalpha-0/0 and
      that the lower T(C) at room temperature (RT, 20-22 C) is caused by a down setting
      of the hypothalamic thermostat. However, TRalpha-0/0 mice are cold intolerant due
      to impaired facultative thermogenesis. Norepinephrine-induced brown adipose
      tissue (BAT) thermogenesis is blunted, even though BAT-relevant genes and T(4)
      deiodinase respond normally to cold stimulation, as do serum T(3), serum glycerol
      (marker of lipolysis), and heart rate. BAT normally contributes to maintain T(C)
      at RT, 9 C below thermoneutrality, yet TRalpha-0/0 mice do not show signs of
      being cold stressed at 20-22 C. Instead, oxygen consumption is greater in TRalpha
      0/0 than in wild-type mice at RT, suggesting the recruitment of an alternate,
      cold-activated form of thermogenesis to compensate for the lack of BAT
      thermogenesis. These results indicate that TRalpha is necessary for T(3) to
      modulate the central control of T(C) and for an essential step in norepinephrine
      activation of BAT thermogenesis but not to sustain obligatory thermogenesis. In
      addition, the results provide evidence for an alternate form of facultative
      thermogenesis, which probably originates in skeletal muscle and that is less
      effective and more energy demanding than BAT thermogenesis.

PMID- 15845619
TI  - Central relaxin-3 administration causes hyperphagia in male Wistar rats.
AB  - Relaxin-3 (INSL-7) is a recently discovered member of the insulin superfamily.
      Relaxin-3 mRNA is expressed in the nucleus incertus of the brainstem, which has
      projections to the hypothalamus. Relaxin-3 binds with high affinity to the LGR7
      receptor and to the previously orphan G protein-coupled receptor GPCR135. GPCR135
      mRNA is expressed predominantly in the central nervous system, particularly in
      the paraventricular nucleus (PVN). The presence of relaxin-3 and these receptors
      in the PVN led us to investigate the effect of central administration of relaxin
      3 on food intake in male Wistar rats. The receptor involved in mediating these
      effects was also investigated. Intracerebroventricular injections of human
      relaxin-3 (H3) to satiated rats significantly increased food intake 1 h post
      administration in the early light phase [0.96 +/- 0.16 g (vehicle) vs. 1.81 +/-
      0.21 g (180 pmol H3), P < 0.05] and the early dark phase [2.95 +/- 0.45 g
      (vehicle) vs. 4.39 +/- 0.39 g (180 pmol H3), P < 0.05]. Intra-PVN H3
      administration significantly increased 1-h food intake in satiated rats in the
      early light phase [0.34 +/- 0.16 g (vehicle) vs. 1.23 +/- 0.30 g (18 pmol H3), P
      < 0.05] and the early dark phase [4.43 +/- 0.32 g (vehicle) vs. 6.57 +/- 0.42 g
      (18 pmol H3), P < 0.05]. Feeding behavior increased after intra-PVN H3. Equimolar
      doses of human relaxin-2, which binds the LGR7 receptor but not GPCR135, did not
      increase feeding. Hypothalamic neuropeptide Y, proopiomelanocortin, or agouti
      related peptide mRNA expression did not change after acute
      intracerebroventricular H3. These results suggest a novel role for relaxin-3 in
      appetite regulation.

PMID- 15845620
TI  - Prolactin receptor knockdown in the rat paraventricular nucleus by a morpholino
      antisense oligonucleotide causes hypocalcemia and stress gastric erosion.
AB  - Under acute stress conditions in the rat, there is rapid and transient increase
      in circulating prolactin (PRL). This leads to an elevated expression of the long
      form of PRLR (PRLR-L) first in the hypothalamus and the choroid plexus. This
      increase in PRL is involved in the inhibition of stress-induced hypocalcemia and
      gastric erosion. In this study we used rat PRL and a PRLR morpholino-antisense
      oligonucleotide to elucidate the mechanism by which hypothalamic PRLR mediates
      the inhibition of restraint stress in water (RSW)-induced hypocalcemia and
      gastric erosion. We found that this effect is largely mediated by PRLRs in the
      paraventricular nucleus (PVN), medial preoptic nucleus, and ventromedial
      hypothalamus. We also show that when measured after 7 h of RSW, microinjection of
      the PRLR antisense oligonucleotide into these areas down-regulates RSW-enhanced
      expression of PRLR-L protein in the PVN and increases the plasma PRL level, but
      does not affect plasma levels of another hormone, GH. Furthermore, our
      experiments demonstrated that under nonstress conditions, knockdown of the PRLR
      in the PVN significantly lowers circulating Ca2+ levels, but does not affect
      gastric erosion. These results suggest that PRL acting on the PRLR-L in the PVN
      is one of the critical pathways for regulating circulating Ca2+ levels under both
      acute stress and nonstress conditions.

PMID- 15845621
TI  - Leptin modulates both resorption and formation while preventing disuse-induced
      bone loss in tail-suspended female rats.
AB  - In vitro studies have demonstrated leptin-positive effects on the osteoblast
      lineage and negative effects on osteoclastogenesis. Therefore, we tested the
      hypothesis that leptin may prevent tail-suspension-induced bone loss
      characterized by an uncoupling pattern of bone remodeling, through both
      mechanisms. Female rats were randomly tail-suspended or not and treated either
      with ip administration of leptin or vehicle for 3, 7, and 14 d. As measured by
      dual energy x-ray absorptiometry, tail-suspension induced a progressive decrease
      in tibia-metaphysis bone mineral density, which was prevented by leptin.
      Histomorphometry showed that this was related to the prevention of the transient
      increase in osteoclast number observed with suspension at d 7. These effects
      could be mediated by the receptor activator of nuclear factor kappaB-ligand
      (RANKL)/osteoprotegerin (OPG) pathway since we observed using direct RT-PCR, a
      suspension-induced increase in RANKL gene expression in proximal tibia at d 3,
      which was counterbalanced by leptin administration with a similar 3-fold increase
      in OPG expression and a RANKL to OPG ratio close to nonsuspended conditions. In
      addition, leptin prevented the decrease in bone formation rate induced by tail
      suspension at d 14. The latter could be related to the role of leptin in
      mediating the reciprocal differentiation between adipocytes and osteoblasts,
      because leptin concurrently blunted the disuse-induced increase in bone marrow
      adipogenesis. In summary, these data suggest that peripheral administration of
      leptin could prevent disuse-induced bone loss through, first, a major inhibitory
      effect on bone resorption and, second, a delayed effect preventing the decrease
      in bone formation.

PMID- 15845622
TI  - Altered levels of angiopoietin 1 and tie 2 are associated with androgen-regulated
      vascular regression and growth in the ventral prostate in adult mice and rats.
AB  - The involution of the rat ventral prostate gland after castration could be caused
      by primary changes in the vasculature. To explore the mechanisms, we studied the
      effects of castration and testosterone treatment on the vasculature in the
      ventral prostate in adult rats and mice. Androgen receptor expression, vascular
      morphology, and the expression of angiopoietin (ang) 1 and 2 and their receptor
      tie 2 were examined 1, 3, and 7 d after castration and after testosterone
      treatment of castrated animals using stereological methods, immunohistochemistry,
      laser capture microdissection, and Western blotting. One day after castration,
      the percentage of blood vessels covered with smooth muscle actin, endothelial
      cell proliferation, and vascular volume had decreased, whereas endothelial cell
      apoptosis had increased. Simultaneously, ang 1 and tie 2 protein levels
      decreased. Nuclear expression of androgen receptor was observed not only in
      glandular and stroma smooth muscle cells but also in the mural cells of prostate
      arteries and veins and was markedly down-regulated already 1 d after castration.
      Testosterone administration of castrated mice and rats reversed all the observed
      effects. At the mRNA level, tie 2 was exclusively, but ang 1 predominantly,
      expressed in the stroma, compared with the epithelial compartment. Local delivery
      of soluble tie 2 during testosterone-stimulated growth, inhibited vascular
      maturation and increased vascular volume and leukocyte infiltration compared with
      controls. We conclude that androgens may regulate the prostate vasculature by
      direct effects on mural vascular cells and by influencing the secretion of the
      angiopoietins, in above all, the stroma cells.

PMID- 15845623
TI  - Interleukin-6 depletion selectively improves hepatic insulin action in obesity.
AB  - Obesity and insulin resistance are considered chronic inflammatory states, in
      part because circulating IL-6 is elevated. Exogenous IL-6 can induce hepatic
      insulin resistance in vitro and in vivo. The importance of endogenous IL-6,
      however, to insulin resistance of obesity is unresolved. To test the hypothesis
      that IL-6 contributes to the inflammation and insulin resistance of obesity, IL-6
      was depleted in Lep(ob) mice by injection of IL-6-neutralizing antibody. In
      untreated Lep(ob) mice, signal transducer and activator of transcription-3
      (STAT3) activation was increased compared with that in lean controls, consistent
      with an inflammatory state. With IL-6 depletion, activation of STAT3 in liver and
      adipose tissue and expression of haptoglobin were reduced. Expression of the IL-6
      dependent, hepatic acute phase protein fibrinogen was also decreased. Using the
      hyperinsulinemic-euglycemic clamp technique, insulin-dependent suppression of
      endogenous glucose production was 89% in IL-6-depleted Lep(ob) mice, in contrast
      to only 32% in Lep(ob) controls, indicating a marked increase in hepatic insulin
      sensitivity. A significant change in glucose uptake in skeletal muscle after IL-6
      neutralization was not observed. In a direct comparison of hepatic insulin
      signaling in Lep(ob) mice treated with anti-IL-6 vs. IgG-treated controls,
      insulin-dependent insulin receptor autophosphorylation and activation of Akt
      (pSer473) were increased by nearly 50% with IL-6 depletion. In adipose tissue,
      insulin receptor signaling showed no significant change despite major reductions
      in STAT3 phosphorylation and haptoglobin expression. In diet-induced obese mice,
      depletion of IL-6 improved insulin responsiveness in 2-h insulin tolerance tests.
      In conclusion, these results indicate that IL-6 plays an important and selective
      role in hepatic insulin resistance of obesity.

PMID- 15845624
TI  - Insulin-like growth factor (IGF)-I stimulates cell proliferation and induces IGF
      binding protein (IGFBP)-3 and IGFBP-5 gene expression in cultured growth plate
      chondrocytes via distinct signaling pathways.
AB  - The bioactivity of IGF-I in the cellular microenvironment is modulated by both
      inhibitory and stimulatory IGF binding proteins (IGFBPs), whose production is
      partially under control of IGF-I. However, little is known on the IGF-mediated
      regulation of these IGFBPs in the growth plate. We therefore studied the effect
      of IGF-I on IGFBP synthesis and the involved intracellular signaling pathways in
      two cell culture models of rat growth plate chondrocytes. In growth plate
      chondrocytes in primary culture, incubation with IGF-I increased the
      concentrations of IGFBP-3 and IGFBP-5 in conditioned cell culture medium in a
      dose- and time-dependent manner. Coincubation of IGF-I with specific inhibitors
      of the p42/44 MAPK pathway (PD098059 or U0126) completely abolished the
      stimulatory effect of IGF-I on IGFBP-3 mRNA expression but did not affect
      increased IGFBP-5 mRNA levels. In contrast, inhibition of the
      phosphatidylinositol-3 kinase signaling pathway by LY294002 abrogated both IGF-I
      stimulated IGFBP-3 and -5 mRNA expression. Comparable results regarding IGFBP-5
      were obtained in the mesenchymal chondrogenic cell line RCJ3.1C5.18, which does
      not express IGFBP-3. The IGF-I-induced IGFBP-5 gene expression required de novo
      mRNA transcription and de novo protein synthesis. These data suggest that IGF-I
      modulates its activity in cultured rat growth plate chondrocytes by the synthesis
      of both inhibitory (IGFBP-3) and stimulatory (IGFBP-5) binding proteins. The
      finding that IGF-I uses different and only partially overlapping intracellular
      signaling pathways for the regulation of two IGFBPs with opposing biological
      functions might be important for the modulation of IGF bioactivity in the
      cellular microenvironment.

PMID- 15845625
TI  - Insulin receptor substrates-1 and -2 are both depleted but via different
      mechanisms after down-regulation of glucose transport in rat adipocytes.
AB  - Alterations in muscle and adipose tissue insulin receptor substrate (IRS)-1 and
      IRS-2 are associated with, and commonly believed to contribute to, development of
      insulin resistance. In this study, we investigated the mechanisms behind
      previously observed reductions in IRS levels due to high concentrations of
      glucose and insulin and their significance in the impairment of glucose uptake
      capacity in primary rat adipocytes. Semiquantitative RT-PCR analysis showed that
      insulin (10(4) microU/ml) alone or in combination with glucose (15 mm) markedly
      suppressed IRS-2 gene expression, whereas IRS-1 mRNA was unaffected by the
      culture conditions. The negative effect of a high glucose/high insulin setting on
      IRS-1 protein level was still exerted when protein synthesis was inhibited with
      cycloheximide. Impairment of glucose uptake capacity after treatment with high
      glucose and insulin was most pronounced after 3 h, whereas IRS-1 and IRS-2
      protein levels were unaffected up to 6 h but were reduced after 16 h. Moreover,
      impaired glucose uptake capacity could only partially be reversed by subsequent
      incubation at physiological conditions. These novel results suggest that: 1) in a
      high glucose/high insulin setting depletion of IRS-1 and IRS-2 protein,
      respectively, occurs via different mechanisms, and IRS-2 gene expression is
      suppressed, whereas IRS-1 depletion is due to posttranslational mechanisms; 2)
      IRS-1 and IRS-2 protein depletion is a secondary event in the development of
      insulin resistance in this model of hyperglycemia/hyperinsulinemia; and 3)
      depletion of cellular IRS in adipose tissue may be a consequence rather than a
      cause of insulin resistance and hyperinsulinemia in type 2 diabetes.

PMID- 15845626
TI  - Time-resolved sex differences in language lateralization.

PMID- 15845628
TI  - Sex difference in language lateralization may be task-dependent.

PMID- 15845632
TI  - Establishing preconditions for Balo's concentric sclerosis.

PMID- 15845634
TI  - Selective inhibitors differentially affect cyclooxygenase-dependent pial
      arteriolar responses in newborn pigs.
AB  - Cyclooxygenase (COX)-derived prostanoids play an important role in the
      cerebrovascular control of newborns. In humans and in the widely accepted model
      of piglets, both the COX-1 and the COX-2 isoforms are expressed in cerebral
      arteries. However, the involvement of these isoforms in cerebrovascular control
      is unknown. Therefore we tested if specific inhibitors of COX-1 and/or COX-2
      would differentially affect pial arteriolar responses to COX-dependent stimuli in
      piglets. Anesthetized, ventilated piglets (n = 35) were equipped with a closed
      cranial window, and changes in pial arteriolar diameters (baseline approximately
      100 microm) to hypercapnia (ventilation with 5-10% CO(2), 21% O(2), balance
      N(2)), arterial hypotension (40 mm Hg MABP achieved by blood withdrawal), and Ach
      (Ach, 10-100 microM) were determined via intravital microscopy. Arteriolar
      responses were repeatedly tested 15 min after IV administration of selective COX
      1 and COX-2 inhibitors SC-560 and NS-398 (1-1 mg/kg), and nonselective inhibitors
      indomethacin (0.3-1 mg/kg), acetaminophen (30 mg/kg), and ibuprofen (30 mg/kg).
      Hypercapnia resulted in concentration-dependent, reversible, (approximately 20
      40%) increases in pial arteriolar diameters that were unaffected by NS-398, SC
      560, acetaminophen and ibuprofen. In contrast, 0.3 mg/kg indomethacin
      significantly reduced, 1 mg/kg virtually abolished the vasodilation. Arterial
      hypotension elicited (approximately 15-20%) vasodilation that was similarly
      reduced by NS-398 and indomethacin but was unaltered by SC-560. Ach dose
      dependently constricted pial arterioles. This response was similarly attenuated
      by NS-398, indomethacin, and ibuprofen, but left intact by SC-560. We conclude
      that the assessed COX-dependent vascular reactions appear to depend largely on
      COX-2 activity. However, hypercapnia-induced vasodilation was found indomethacin
      sensitive instead of a COX-dependent response in the piglet.

PMID- 15845635
TI  - Expression of osteopontin correlates with portal biliary proliferation and
      fibrosis in biliary atresia.
AB  - The acquired or perinatal form of biliary atresia is a Th1 fibro-inflammatory
      disease affecting both the extrahepatic and intrahepatic bile ducts. Osteopontin
      (OPN) is a Th1 cytokine implicated in several fibro-inflammatory and autoimmune
      diseases. We examined the expression of OPN in acquired biliary atresia in
      comparison to normal liver and several pediatric cholestatic liver diseases. We
      also assessed OPN expression by cultured human bile duct epithelial cells. We
      found that liver OPN mRNA and protein expression were significantly increased in
      biliary atresia versus normal and other cholestatic diseases. OPN expression in
      biliary atresia was localized to epithelium of proliferating biliary structures
      (ductules and/or ducts) and bile plugs contained therein. No portal biliary OPN
      expression could be demonstrated in normal liver, syndromic biliary atresia,
      biliary obstruction not due to biliary atresia, and idiopathic neonatal
      hepatitis. OPN expression by human bile duct epithelial cells in culture was
      responsive to IL-2 and TNF-alpha. Our results demonstrate an up-regulation of OPN
      expression by interlobular biliary epithelium in biliary atresia, which
      correlates with biliary proliferation and portal fibrosis. These findings suggest
      a role for OPN in the pathogenesis of biliary atresia.

PMID- 15845636
TI  - Long-chain fatty acid oxidation during early human development.
AB  - Patients with very long-chain acyl-CoA dehydrogenase (VLCAD) and long-chain 3
      hydroxyacyl-CoA dehydrogenase (LCHAD)/mitochondrial trifunctional protein (MTP)
      deficiency, disorders of the mitochondrial long-chain fatty acid oxidation, can
      present with hypoketotic hypoglycemia, rhabdomyolysis, and cardiomyopathy. In
      addition, patients with LCHAD/MTP deficiency may suffer from retinopathy and
      peripheral neuropathy. Until recently, there was no indication of intrauterine
      morbidity in these disorders. This observation was in line with the widely
      accepted view that fatty acid oxidation (FAO) does not play a significant role
      during fetal life. However, the high incidence of the gestational complications
      acute fatty liver of pregnancy and hemolysis, elevated liver enzymes, and low
      platelets syndrome observed in mothers carrying a LCHAD/MTP-deficient child and
      the recent reports of fetal hydrops due to cardiomyopathy in MTP deficiency, as
      well as the high incidence of intrauterine growth retardation in children with
      LCHAD/MTP deficiency, suggest that FAO may play an important role during fetal
      development. In this study, using in situ hybridization of the VLCAD and the
      LCHAD mRNA, we report on the expression of genes involved in the mitochondrial
      oxidation of long-chain fatty acids during early human development. Furthermore,
      we measured the enzymatic activity of the VLCAD, LCHAD, and carnitine palmitoyl
      CoA transferase 2 (CPT2) enzymes in different human fetal tissues. Human embryos
      (at d 35 and 49 of development) and separate tissues (5-20 wk of development)
      were used. The results show a strong expression of VLCAD and LCHAD mRNA and a
      high enzymatic activity of VLCAD, LCHAD, and CPT2 in a number of tissues, such as
      liver and heart. In addition, high expression of LCHAD mRNA was observed in the
      neural retina and CNS. The observed pattern of expression during early human
      development is well in line with the spectrum of clinical signs and symptoms
      reported in patients with VLCAD or LCHAD/MTP deficiency.

PMID- 15845637
TI  - Surprising? Perhaps not. Long-chain fatty acid oxidation during human fetal
      development.

PMID- 15845638
TI  - Age-related differences in vasoconstrictor responses to isoprostanes in piglet
      pulmonary and mesenteric vascular smooth muscle.
AB  - Isoprostanes are prostaglandin (PG)-like compounds produced nonenzymatically by
      free radical-catalyzed peroxidation of arachidonic acid. Isoprostanes evoke
      potent vascular effects but their actions in the neonatal vasculature are poorly
      known. We aimed to study the effects of 8-iso-PGE(1), 8-iso-PGE(2), 8-iso
      PGF(1alpha), 8-iso-PGF(1beta), 8-iso-PGF(2alpha), and 8-iso-PGF(2beta) in
      pulmonary arteries (PA), pulmonary veins (PV), and mesenteric arteries (MA) from
      newborn and 2-wk-old piglets. Isoprostanes produced concentration-dependent
      contractions of PA, PV, and MA (magnitudes up to 1.5- to 2-fold greater than the
      responses to 62.5 mM KCl) but they were markedly less potent vasoconstrictors
      than the thromboxane A(2) (TXA(2)) mimetic U46619. Neonatal PA were more
      sensitive to 8-iso-PGF(1alpha), 8-iso-PGF(1beta), and 8-iso-PGF(2beta) than 2-wk
      old PA. Neonatal PV were more sensitive to 8-iso-PGE(2) and 8-iso-PGF(1alpha),
      and neonatal MA were more sensitive to 8-iso-PGE(2), 8-iso-PGF(1alpha), 8-iso
      PGF(1beta), 8-iso-PGF(2alpha), and 8-iso-PGF(2beta) than the corresponding 2-wk
      old vessels. The sensitivity to U46619 decreased with postnatal age in MA but did
      not change in PA and PV. The contractile responses to all the isoprostanes and to
      U46619 were reverted by the TXA(2) receptor (TP) antagonist SQ 29,548. Moreover,
      isoprostane-evoked contractions in 2-wk-old PA were reduced by inhibitors of
      tyrosine kinase (genistein) and Rho kinase (Y 27632 and hydroxyfasudil) but not
      by inhibitors of protein kinase C (chelerythrine), mitogen-activated protein
      kinase kinase (PD 98059) or p38-kinase (SB 203580). In conclusion, isoprostanes
      produced compound-, tissue-, and age-dependent constriction of neonatal porcine
      pulmonary and mesenteric vascular smooth muscle. Isoprostane-evoked PA
      vasoconstriction involved TP receptors and activation of tyrosine kinases and Rho
      kinases.

PMID- 15845639
TI  - Single subcutaneous administration of chorionic gonadotropin to rats induces a
      rapid and transient increase in testicular expression of pro-inflammatory
      cytokines.
AB  - hCG has been reported to cause an inflammation-like effect in the testis,
      although the background and consequences of this phenomenon remain to be
      understood. This investigation reveals that a single injection of hCG (100 U)
      induces a transient surge in pro-inflammatory cytokine expression in the adult
      rat testis. Reverse transcriptase PCR analysis demonstrated onset of testicular
      expression of IL-1beta and IL-6 mRNA and increases in the levels of mRNA encoding
      the constitutively expressed cytokines IL-1alpha, IL-1 receptor antagonist, and
      tumor necrosis factor-alpha 4 h after hCG injection and a maximal response after
      8-12 h. These increases were accompanied by a transient increase in testicular IL
      1 bioactive protein. Twenty-four hours after administration of hCG, the levels of
      all cytokine mRNA had decreased, although most were still elevated above control.
      Immunohistochemical staining revealed that the IL-1beta protein was undetectable
      in normal testes but was seen to be localized to interstitial macrophages but not
      Leydig cells after hCG treatment. Testes devoid of Leydig cells after
      pretreatment with ethane dimethane sulphonate exhibited normal staining for
      interstitial macrophages but failed to respond to hCG with increases in IL-1beta
      mRNA and protein expression. We conclude that hCG induces testicular inflammation
      via local activation by Leydig cells of the production of pro-inflammatory
      cytokines by resident macrophages. It remains to be investigated whether the high
      dose hCG regimens used for treatment of boys with cryptorchidism could induce
      similar increases of pro-inflammatory cytokines in the human testis and if such
      treatments could adversely affect future testicular function.

PMID- 15845640
TI  - Thyroid hemiagenesis is a rare variant of thyroid dysgenesis with a familial
      component but without Pax8 mutations in a cohort of 22 cases.
AB  - Thyroid hemiagenesis is a rare form of thyroid dysgenesis of which some familial
      cases have been reported, including one associated with a heterozygous mutation
      in the Pax8 gene. However, the physiopathology remains not well known. The
      objectives of this study were 1) to describe the clinical features, 2) to look
      for familial clustering, and 3) to search for Pax8 mutations in a relatively
      large cohort of affected patients. A family history of thyroid dysgenesis was
      found in nine patients (40%), whose affected relatives had ectopic thyroid (n =
      4), athyreosis (n = 1), thyroid hemiagenesis (n = 2), or thyroglossal duct cysts
      (n = 2). Screening for Pax8 mutations identified abnormal migration profiles by
      SSCP analysis in 3 patients, but direct sequencing did not show coding region
      mutations in any of the 22 patients. In conclusion, this study provides the first
      evidence that thyroid hemiagenesis can occur as a familial disorder associated
      with any form of thyroid dysgenesis. This finding supports both a common
      underlying mechanism to the various abnormalities in thyroid development and a
      role for genetic factors; however, our results from Pax8 analysis suggest that
      this gene may not be a key factor.

PMID- 15845641
TI  - Mild neonatal hypoxia exacerbates the effects of vitamin-deficient diet on
      homocysteine metabolism in rats.
AB  - Elevated plasma homocysteine has been linked to pregnancy complications and
      developmental diseases. Whereas hyperhomocysteinemia is frequently observed in
      populations at risk of malnutrition, hypoxia may alter the remethylation of
      homocysteine in hepatocytes. We aimed to investigate the combined influences of
      early deficiency in nutritional determinants of hyperhomocysteinemia and of
      neonatal hypoxia on homocysteine metabolic pathways in developing rats. Dams were
      fed a standard diet or a diet deficient in vitamins B12, B2, folate, month, and
      choline from 1 mo before pregnancy until weaning of the offspring. The pups were
      divided into four treatment groups corresponding to "no hypoxia/standard diet,"
      "hypoxia (100% N2 for 5 min at postnatal d 1)/standard diet," "no
      hypoxia/deficiency," and "hypoxia/deficiency," and homocysteine metabolism was
      analyzed in their liver at postnatal d 21. Hypoxia increased plasma homocysteine
      in deficient pups (21.2 +/- 1.6 versus 13.3 +/- 1.2 microM, p < 0.05). Whereas
      mRNA levels of cystathionine beta-synthase remained unaltered, deficiency reduced
      the enzyme activity (48.7 +/- 2.9 versus 83.6 +/- 6.3 nmol/h/mg, p < 0.01), an
      effect potentiated by hypoxia (29.4 +/- 4.7 nmol/h/mg, p < 0.05). The decrease in
      methylene-tetrahydrofolate reductase activity measured in deficient pups was
      attenuated by hypoxia (p < 0.05), and methionine-adenosyltransferase activity was
      slightly reduced only in the "hypoxia/deficiency" group (p < 0.05). Finally,
      hypoxia enhanced the deficiency-induced drop of the S-adenosylmethionine/S
      adenosylhomocysteine ratio, which is known to influence DNA methylation and gene
      expression. In conclusion, neonatal hypoxia may increase homocysteinemia mainly
      by decreasing homocysteine transsulfuration in developing rats under methyl
      deficient regimen. It could therefore potentiate the well-known adverse effects
      of hyperhomocysteinemia.

PMID- 15845642
TI  - Mycobacterium bovis Bacillus Calmette-Guerin infects DC-SIGN- dendritic cell and
      causes the inhibition of IL-12 and the enhancement of IL-10 production.
AB  - The only available vaccine against tuberculosis is Mycobacterium bovis Bacillus
      Calmette Guerin (BCG), although its efficacy in preventing pulmonary tuberculosis
      is controversial. Early interactions between dendritic cells (DC) and BCG or
      Mycobacterium tuberculosis (Mtb) are thought to be critical for mounting a
      protective antimycobacterial immune response. Recent studies have shown that BCG
      and Mtb target the DC-specific C-type lectin intercellular adhesion molecule-3
      grabbing nonintegrin (DC-SIGN) to infect DC and inhibit their immunostimulatory
      function. This would occur through the interaction of the mycobacterial
      mannosylated lipoarabinomannan to DC-SIGN, which would prevent DC maturation and
      induce the immunosuppressive cytokine interleukin (IL)-10 synthesis. Here, we
      confirm that DC-SIGN is expressed in DC derived from monocytes cultured in
      granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-4 and show that
      it is not expressed in DC derived from monocytes cultured in GM-CSF and
      interferon-alpha (IFN-alpha). We also demonstrate that DC-SIGN(-) DC cultured in
      GM-CSF and IFN-alpha are able to phagocytose BCG and to undergo a maturation
      program as well as DC-SIGN(+) DC cultured in IL-4 and GM-CSF. We also show that
      BCG causes the impairment of IL-12 and the induction of IL-10 secretion by DC,
      irrespective of DC-SIGN expression. Finally, we demonstrate that the capacity to
      stimulate a mixed leukocyte reaction of naive T lymphocytes is not altered by the
      treatment of both DC populations with BCG. These data suggest that DC-SIGN cannot
      be considered as the unique DC receptor for BCG internalization, and it is more
      interesting that the mycobacteria-induced immunosuppression cannot be attributed
      to the engagement of a single receptor.

PMID- 15845643
TI  - Type I and type II interferons delay human neutrophil apoptosis via activation of
      STAT3 and up-regulation of cellular inhibitor of apoptosis 2.
AB  - We have recently demonstrated that granulocyte-colony stimulating factor (G-CSF)
      delays human neutrophil apoptosis via up-regulation of cellular inhibitor of
      apoptosis 2 (cIAP2), which is dependent on activation of Janus kinase 2 (JAK2)
      and signal transducer and activator of transcription 3 (STAT3). Here, we show
      that type I and type II interferons (IFNs), which bind to the distinct receptors,
      exert the antiapoptotic effect on human neutrophils through the similar
      mechanism. IFN-alpha (type I IFN) and IFN-gamma (type II IFN), like G-CSF,
      delayed human neutrophil apoptosis through the protein synthesis-dependent
      mechanism. Stimulation of neutrophils with IFN-alpha or IFN-gamma resulted in
      tyrosine phosphorylation of STAT1 and STAT3 but not phosphorylation of STAT5,
      Akt, extracellular signal-regulated kinase, and p38 mitogen-activated protein
      kinase. IFN-alpha and IFN-gamma induced the expression of transcripts of cIAP2
      and suppressor of cytokine signaling 1 and 3, but not cIAP1, Mcl-1, and A1. IFN
      alpha- and IFN-gamma-induced up-regulation of cIAP2 mRNA and protein,
      phosphorylation of STAT3, and antiapoptotic effect were inhibited significantly
      by pretreatment of cells with AG490, a specific inhibitor of JAK2. These findings
      suggest that cIAP2 expression is up-regulated by IFN-alpha and IFN-gamma through,
      at least in part, activation of the JAK2-STAT3 pathway, and increased expression
      of the cIAP2 protein may contribute to an IFN-alpha- and IFN-gamma-mediated
      antiapoptotic effect on human neutrophils.

PMID- 15845645
TI  - BALB/c mice have more CD4+CD25+ T regulatory cells and show greater
      susceptibility to suppression of their CD4+CD25- responder T cells than C57BL/6
      mice.
AB  - Increasing evidence indicates that CD4(+)CD25(+) T regulatory (Treg) cells
      control a wide spectrum of immune responses. The initial identification of
      CD4(+)CD25(+) Treg cell as a "professional suppressor" was based on observations
      made in BALB/c mice. This mouse strain is well known to preferentially develop T
      helper cell type 2 responses, to be more susceptible to intracellular parasite
      infection, to have a higher tumor incidence, and to be more resistant to the
      induction of autoimmune diseases, as compared with C57BL/6 (B6) mice. We
      therefore decided to compare Treg cell function of B6 and BALB/c mice. We
      observed that the frequency of CD4(+)CD25(+) T cells in the thymus and peripheral
      lymphoid organs of BALB/c mice was higher than in B6 mice. CD4(+)CD25(+) Treg
      cells from both mouse strains shared similar phenotypic properties, including
      expression of characteristic immunological markers and hyporesponsiveness to T
      cell receptor cross-linking and in their capacity to suppress proliferation of
      BALB/c CD4(+)CD25(-) T responder (Tres) cells. However, CD4(+)CD25(-) Tres cells
      from B6 mice were notably less susceptible to suppression by CD4(+)CD25(+) Treg
      cells from either mouse strain. Our data suggest that the number and the level of
      suppression of CD4(+)CD25(+) Treg cells for CD4(+)CD25(-) Tres cells may be
      dictated by genetic background. Our data also suggest that differences in the
      CD4(+)CD25(+) Treg cell number and the susceptibility of CD4(+)CD25(-) Tres cells
      may, at least in part, account for the differences in immune response between B6
      and BALB/c strains of mice.

PMID- 15845644
TI  - Up-regulation of GRP78 and antiapoptotic signaling in murine peritoneal
      macrophages exposed to insulin.
AB  - The unfolded protein response pathway (UPR) compensates for excessive protein
      accumulation in the endoplasmic reticulum (ER). As insulin induces global protein
      synthesis, it may cause accumulation of unfolded proteins in the ER, thus
      triggering UPR. We assessed UPR activation in insulin-treated murine peritoneal
      macrophages using a number of markers including 78 kDa glucose response protein
      (GRP78), X-box-binding protein (XBP)-1, pancreatic ER kinase (PERK), eukaryotic
      initiation factor 2 (eIF2)alpha, and growth arrest and DNA damage (GADD)34.
      Exposure of cells to insulin activated UPR, as evidenced by an increased
      expression of GRP78, XBP-1, phosphorylated PERK (p-PERK), and p-eIF2alpha. The
      insulin-induced, elevated expression of GRP78 was comparable with that observed
      with tunicamycin, a classical inducer of ER stress. Concomitantly, insulin also
      up-regulated prosurvival mechanisms by elevating GADD34 and elements of the
      antiapoptotic pathway including Bcl-2, X-linked inhibitor of apoptosis, and
      phosphorylated forkhead transcription factor. In conclusion, we show here that
      insulin treatment does cause ER stress in macrophages, but insulin-dependent
      mechanisms overcome this ER stress by up-regulating UPR and the antiapoptotic
      pathway to promote cell survival.

PMID- 15845646
TI  - ER-mediated phagocytosis: myth or reality?

PMID- 15845647
TI  - Reduced endocannabinoid immune modulation by a common cannabinoid 2 (CB2)
      receptor gene polymorphism: possible risk for autoimmune disorders.
AB  - Immune system responsiveness results from numerous factors, including endogenous
      cannabinoid signaling in immunocytes termed the "immunocannabinoid" system. This
      system can be an important signaling pathway for immune modulation. To assess the
      immunomodulating role of the cannabinoid 2 (CB2) receptor, we sought
      polymorphisms in the human gene, identified a common dinucleotide polymorphism,
      and investigated its effect on endocannabinoid-induced inhibition of T lymphocyte
      proliferation. The CB2 cDNA 188-189 GG/GG polymorphism predicts the substitution
      of glutamine at amino acid position 63 by arginine. T lymphocytes from CB2 188
      189 GG/GG homozygotes had approximately twofold reduction of endocannabinoid
      induced inhibition of proliferation compared with cells from CB2 188-189 AA/AA
      homozygotes. In GG/GG subjects, the reduced endocannabinoid inhibitory response
      was highly significant for N-arachidonylglycine and nearly significant for 2
      arachidonylglycerol, and a specific CB2 receptor antagonist partially blocked
      these effects. Also, patients with autoimmune diseases had an increased
      prevalence of the homozygous GG/GG genotype. Collectively, these results
      demonstrate reduced endogenous fatty acid amide immunomodulatory responses in
      individuals with the CB2 188-189 GG/GG genotype and suggest that this CB2 gene
      variation may be a risk factor for autoimmunity. The results also support the
      proposition that the CB2 receptor may represent a novel pharmacological target
      for selective agonists designed to suppress autoreactive immune responses while
      avoiding CB1 receptor-mediated cannabinoid adverse effects.

PMID- 15845648
TI  - TNF-alpha promotes a stop signal that inhibits neutrophil polarization and
      migration via a p38 MAPK pathway.
AB  - Neutrophils are a major component of the inflammatory response in patients with
      asthma and other inflammatory conditions. Proinflammatory cytokines, such as
      tumor necrosis factor alpha (TNF-alpha), are increased in the airway of patients
      with severe asthma and have been implicated in the recruitment of neutrophils
      into areas of inflammation. Here, we show that TNF-alpha induces a stop signal
      that promotes firm neutrophil adhesion and inhibits neutrophil polarization and
      chemotaxis to chemoattractants including interleukin-8 and C5a. TNF-alpha
      treatment of neutrophils plated on a fibrinogen-coated surface promotes firm
      neutrophil adhesion and the formation of vinculin-containing focal complexes. TNF
      alpha induces a more than tenfold increase in p38 mitogen-activated protein
      kinase (MAPK) but not extracellular signal-regulated kinase phosphorylation.
      Inhibition of p38 MAPK in neutrophils treated with TNF-alpha causes neutrophil
      polarization and motility. These findings suggest that TNF-alpha initiates a stop
      signal through a p38 MAPK pathway, which may promote the retention of neutrophils
      in inflammatory sites. Together, our data suggest that inhibition of p38 MAPK may
      be an attractive target to limit inflammatory responses that are mediated by TNF
      alpha.

PMID- 15845649
TI  - Gene expression profiling of NMU-induced rat mammary tumors: cross species
      comparison with human breast cancer.
AB  - Breast cancer is a complex genetic disease characterized by the accumulation of
      multiple molecular alterations. The NMU breast cancer model induced in the rat is
      used for the study of mammary carcinogenesis because it closely mimics human
      breast disease. To assess the validity of this model from a more global molecular
      perspective, and also to devise a general technique to compare animal profiles
      with human microarray studies, we have characterized 25 NMU-induced mammary
      tumors and 11 normal glands using a combination of immunohistochemical and
      microarray analyses. The rat mammary carcinomas were classified as non-invasive,
      ER-positive ductal carcinomas with a composition of differentiated epithelial and
      myoepithelial cell lineages. Gene expression profiles generated using rat
      Affymetrix arrays containing 15,866 genes demonstrated that the rat mammary
      tumors are homogeneous and that H-ras mutations did not confer a unique molecular
      signature. We compared the resulting rat profiles with those obtained from a
      human dataset by merging the raw microarray data, using an approach that involves
      a combination of cross-species and cross-platform analysis. Using this novel
      strategy, we demonstrate the ability of 2305 rat orthologs to recapitulate the
      classification of human tumors derived from human Affymetrix arrays. The gene
      expression profiles of the NMU-induced primary tumors were most similar to ER
      positive, low to intermediate grade breast cancer. Our technique provides a means
      to correlate gene expression data from animal models of cancer to human cancer
      and disease states.

PMID- 15845650
TI  - Penta-O-galloyl-beta-D-glucose suppresses tumor growth via inhibition of
      angiogenesis and stimulation of apoptosis: roles of cyclooxygenase-2 and mitogen
      activated protein kinase pathways.
AB  - Recent studies have revealed that 1,2,3,4,6-penta-O-galloyl-beta-d-glucose (PGG)
      has anti-tumorigenic activity in vitro. In the present work, we evaluated the in
      vitro and in vivo antiangiogenic and antitumor activities of PGG and examined its
      molecular mechanisms. PGG significantly inhibited the proliferation and tube
      formation in basic fibroblast growth factor (bFGF)-treated human umbilical vein
      endothelial cells (HUVECs) at non-cytotoxic concentrations. PGG effectively
      disrupted the bFGF-induced neo-vascularization in chick chorioallantoic membrane
      (CAM) and in Matrigel plugs in the mice. When mice were intraperitoneally
      injected, PGG also significantly inhibited tumor angiogenesis induced by Lewis
      lung carcinoma (LLC) and the growth of LLC by 57 and 91% of control tumor weight
      at 4 and 20 mg/kg, respectively. Immunohistochemical analysis revealed decreased
      microvessel density, decreased expression of cyclooxygenase-2 (COX-2) and
      vascular endothelial growth factor (VEGF), reduced tumor cell proliferation and
      increased tumor cell apoptosis. Similarly, PGG significantly attenuated the
      expression of COX-2 and VEGF and reduced the secretion of VEGF and prostaglandin
      E2 in bFGF-treated HUVECs. Furthermore, the COX-2 inhibitor NS398 significantly
      inhibited tube formation and neo-vascularization in CAM, supporting the role of
      COX-2 in PGG inhibition of angiogenesis. PGG diminished the phosphorylation of
      extracellular signal regulated kinase 1/2, Jun NH2-terminal kinase and activated
      phospho-p38 mitogen-activated protein kinase (MAPK) in a dose-dependent manner in
      bFGF-treated HUVECs. In addition, p38 inhibitor SB203580 abolished the
      downregulation of COX-2, VEGF and the antiproliferative activity by PGG. Taken
      together, our data demonstrate that PGG exerts antitumor activity primarily via
      inhibition of angiogenesis through COX-2 and MAPK- dependent pathways.

PMID- 15845651
TI  - PKB/AKT and ERK regulation of caspase-mediated apoptosis by methylseleninic acid
      in LNCaP prostate cancer cells.
AB  - Methylselenol has been implicated as an active metabolite for the anticancer
      effect of selenium in part through the induction of cancer cell apoptosis. Since
      inactivation of the AKT/protein kinase B negative regulator gene PTEN
      (phosphatase and tensin homologue deleted on chromosome 10) is common in prostate
      cancer (PCa), we compared PTEN wild-type DU145 PCa cells (low basal AKT activity)
      with PTEN-mutant LNCaP PCa cells (high basal AKT activity) for their apoptosis
      responses to the methylselenol precursor methylseleninic acid (MSeA) and sodium
      selenite, an inorganic salt. Our results show that LNCaP cells withstood
      approximately 4 times higher doses of MSeA than DU145 cells, although they were
      slightly more sensitive than the latter to selenite-induced apoptosis. Treatment
      by MSeA modestly attenuated AKT phosphorylation and increased phospho-ERK1/2 in
      LNCaP cells. Selenite treatment increased the phosphorylation of p53 Ser15 and
      both kinases, but the selenite-induced apoptosis was not influenced by chemical
      inhibitors of either kinase. In contrast, PI3K/AKT inhibitors greatly sensitized
      LNCaP cells to apoptosis induced by MSeA, accompanied by increased mitochondrial
      release of cytochrome c and multiple caspase activation without changing p53
      Ser15 phosphorylation. The apoptosis was further accentuated by extracellular
      signal regulated kinases 1 and 2 (ERK1/2) inhibition without further increase in
      cytochrome c release. The general caspase inhibitor z-VAD-fmk completely blocked
      MSeA-induced apoptosis when both kinases were inhibited, whereas a caspase-8
      inhibitor exerted a greater protection than did a caspase-9 inhibitor.
      Transfection of DU145 cells with a constitutively active AKT increased their
      resistance to MSeA-induced apoptosis. In summary, AKT played an important role in
      regulating apoptosis sensitivity of LNCaP and DU145 cells to MSeA. An MSeA
      induced activation of ERK1/2 in LNCaP cells also contributed to resistance to
      apoptosis. However, these kinases did not significantly regulate caspase-mediated
      apoptosis induced by selenite in LNCaP cells. These findings support the
      differential involvement of these protein kinase pathways in regulating apoptosis
      induction by different forms of selenium.

PMID- 15845652
TI  - The effect of cyclin D1 (CCND1) G870A-polymorphism on breast cancer risk is
      modified by oxidative stress among Chinese women in Singapore.
AB  - Cyclin D1 (CCND1), an intracellular cell-cycle regulatory protein with checkpoint
      function, can promote cell proliferation or induce growth arrest and apoptosis
      depending on the cellular context. We hypothesized that the direction of the
      association between the (CCND1) G870A-polymorphism and breast cancer risk may be
      modified by dietary and genetic factors influencing the oxidant-antioxidant
      balance, such as a dietary pattern with a high intake of n-6 fatty acids and a
      low intake of n-3 fatty acids, or a genetic profile that is deficient in
      glutathione S-transferases. We tested our hypothesis in a case-control study
      nested into the Singapore Chinese Health Study, a prospective investigation of
      diet and cancer in 63,000 Chinese men and women. Genomic DNA collected from 258
      incident cases of breast cancer and 670 female cohort controls was examined for
      CCND1, GSTM1, GSTT1 and GSTP1 genes using fluorogenic 5'-nuclease assay.
      Unconditional logistic regression models were used to assess the effects with
      adjustment for potential confounders. All statistical tests were two-sided. The
      heterozygous CCND1 GA genotype significantly reduced the breast cancer risk in
      all subjects (OR=0.67, 95% CI 0.45-0.99) when compared with the GG genotype. The
      association was restricted to women with a high (above median value) intake level
      of n-6 fatty acids (OR=0.51, 95% CI 0.30-0.87), a low (below median value) intake
      level of the antagonistic marine n-3 fatty acids (OR=0.54, 95% CI 0.32-0.93) or a
      total lack of the antioxidative GSTM1 (OR=0.44, 95% CI 0.25-0.80) or GSTT1 genes
      (OR=0.46, 95% CI 0.24-0.87). The effects were consistently stronger in cases with
      advanced disease. The AA genotype did not affect breast cancer risk. The results
      of this study are compatible with the hypothesis that the oxidant-antioxidant
      balance in cells is an important determinant of the direction of the cyclin D1
      effect, leading either to cell proliferation or cell death.

PMID- 15845653
TI  - Tectorigenin and other phytochemicals extracted from leopard lily Belamcanda
      chinensis affect new and established targets for therapies in prostate cancer.
AB  - Isoflavones have been shown to exert antiproliferative effects on cancer cells by
      steroid receptor signaling. In this study, we demonstrate the potential of plant
      constituents extracted from Belamcanda chinensis as anticancer drugs, which
      regulate the aberrant expression of genes relevant in proliferation, invasion,
      immortalization and apoptosis. LNCaP cells were treated with B.chinensis extract,
      tectorigenin or other isoflavones and mRNA expression was quantified by using
      real time RT-PCR. In addition, ELISA, TRAP assays and western blots were used to
      measure protein expression or activity. Male nude mice (n=18) were injected
      subcutaneously with LNCaP cells and were fed with extracts from B.chinensis, and
      tumor development was monitored versus a control animal group (n=18).
      Tectorigenin and several other phytochemicals downregulated PDEF, PSA and IGF-1
      receptor mRNA expression in vitro. Furthermore, PSA secretion and IGF-1 receptor
      protein expression were diminished, and hTERT mRNA expression and telomerase
      activity decreased after tectorigenin treatments. However, TIMP-3 mRNA was
      upregulated on tectorigenin treatment. Growth of subcutaneous tumors in nude mice
      was delayed and diminished in animals fed with extracts from B.chinensis. The
      downregulation of PDEF, PSA, hTERT and IGF-1 receptor gene expression by
      tectorigenin demonstrates the antiproliferative potential of these agents. The
      upregulation of TIMP-3 gene expression indicates a pro-apoptotic function of the
      drug and a reduction of the invasiveness of tumors. The animal experiments
      demonstrate that B.chinensis markedly inhibited the development of tumors in
      vivo. Thus, these compounds may be useful for the prevention or treatment of
      human prostate cancer.

PMID- 15845654
TI  - Sample size for FDR-control in microarray data analysis.
AB  - We consider identifying differentially expressing genes between two patient
      groups using microarray experiment. We propose a sample size calculation method
      for a specified number of true rejections while controlling the false discovery
      rate at a desired level. Input parameters for the sample size calculation include
      the allocation proportion in each group, the number of genes in each array, the
      number of differentially expressing genes and the effect sizes among the
      differentially expressing genes. We have a closed-form sample size formula if the
      projected effect sizes are equal among differentially expressing genes.
      Otherwise, our method requires a numerical method to solve an equation.
      Simulation studies are conducted to show that the calculated sample sizes are
      accurate in practical settings. The proposed method is demonstrated with a real
      study.

PMID- 15845655
TI  - Classification of oligonucleotide fingerprints: application for microbial
      community and gene expression analyses.
AB  - MOTIVATION: Oligonucleotide fingerprinting of ribosomal RNA genes (OFRG) is a
      procedure that sorts rRNA gene (rDNA) clones into taxonomic groups through a
      series of hybridization experiments. The hybridization signals are classified
      into three discrete values 0, 1 and N, where 0 and 1, respectively, specify
      negative and positive hybridization events and N designates an uncertain
      assignment. This study examined various approaches for classifying the values
      including Bayesian classification with normally distributed signal data, Bayesian
      classification with the exponentially distributed data, and with gamma
      distributed data, along with tree-based classification. All classification data
      were clustered using the unweighted pair group method with arithmetic mean.
      RESULTS: The performance of each classification/clustering procedure was compared
      with results from known reference data. Comparisons indicated that the approach
      using the Bayesian classification with normal densities followed by tree
      clustering out-performed all others. The paper includes a discussion of how this
      Bayesian approach may be useful for the analysis of gene expression data.

PMID- 15845656
TI  - Donuts, scratches and blanks: robust model-based segmentation of microarray
      images.
AB  - MOTIVATION: Inner holes, artifacts and blank spots are common in microarray
      images, but current image analysis methods do not pay them enough attention. We
      propose a new robust model-based method for processing microarray images so as to
      estimate foreground and background intensities. The method starts with a very
      simple but effective automatic gridding method, and then proceeds in two steps.
      The first step applies model-based clustering to the distribution of pixel
      intensities, using the Bayesian Information Criterion (BIC) to choose the number
      of groups up to a maximum of three. The second step is spatial, finding the large
      spatially connected components in each cluster of pixels. The method thus
      combines the strengths of the histogram-based and spatial approaches. It deals
      effectively with inner holes in spots and with artifacts. It also provides a
      formal inferential basis for deciding when the spot is blank, namely when the BIC
      favors one group over two or three. RESULTS: We apply our methods for gridding
      and segmentation to cDNA microarray images from an HIV infection experiment. In
      these experiments, our method had better stability across replicates than a fixed
      circle segmentation method or the seeded region growing method in the SPOT
      software, without introducing noticeable bias when estimating the intensities of
      differentially expressed genes. AVAILABILITY: spotSegmentation, an R language
      package implementing both the gridding and segmentation methods is available
      through the Bioconductor project (http://www.bioconductor.org). The segmentation
      method requires the contributed R package MCLUST for model-based clustering
      (http://cran.us.r-project.org). CONTACT: fraley@stat.washington.edu.

PMID- 15845657
TI  - MollDE: a homology modeling framework you can click with.
AB  - Molecular Integrated Development Environment (MolIDE) is an integrated
      application designed to provide homology modeling tools and protocols under a
      uniform, user-friendly graphical interface. Its main purpose is to combine the
      most frequent modeling steps in a semi-automatic, interactive way, guiding the
      user from the target protein sequence to the final three-dimensional protein
      structure. The typical basic homology modeling process is composed of building
      sequence profiles of the target sequence family, secondary structure prediction,
      sequence alignment with PDB structures, assisted alignment editing, side-chain
      prediction and loop building. All of these steps are available through a
      graphical user interface. MolIDE's user-friendly and streamlined interactive
      modeling protocol allows the user to focus on the important modeling questions,
      hiding from the user the raw data generation and conversion steps. MolIDE was
      designed from the ground up as an open-source, cross-platform, extensible
      framework. This allows developers to integrate additional third-party programs to
      MolIDE. AVAILABILITY: http://dunbrack.fccc.edu/molide/molide.php CONTACT:
      rl_dunbrack@fccc.edu.

PMID- 15845658
TI  - Nicholas Greene: an academician's academician.

PMID- 15845659
TI  - Postoperative analgesia with remifentanil in patients undergoing cardiac surgery.
AB  - Remifentanil, a short-acting opioid, is commonly used in cardiac anesthesia. In
      this study we sought to demonstrate the feasibility of pain treatment and to
      determine the remifentanil dose necessary for adequate analgesia in tracheally
      extubated patients after cardiac surgery. Thirty patients undergoing elective
      cardiac surgery were included in this study. After surgery, the intraoperatively
      administered remifentanil was initially continued at 0.05 microg . kg(-1) . min(
      1). Before tracheal extubation, a nonsteroidal antiinflammatory drug was
      administered and remifentanil was reduced to 0.035 microg . kg(-1) . min(-1).
      Pain assessment using a visual analog scale (VAS) was performed after tracheal
      extubation, in 2-min intervals for 10 min, every 10 min until the end of the
      first hour and every 30 min during the ensuing 5 h. A VAS score > or =30 or a
      respiratory rate <10 breaths/min was followed by an increase or decrease in the
      remifentanil dose by 0.005 microg . kg(-1) . min(-1), respectively. For rapid
      dose adaptation during the first 10 min, remifentanil was increased twice by
      0.005 microg. kg(-1) . min(-1) and then 3 times by 0.01 microg . kg(-1) . min(
      1). With a mean remifentanil dose of 0.051 microg . kg(-1) . min(-1) VAS
      decreased to 26 +/- 14 after 30 min. Sufficient analgesia was achieved with
      remifentanil doses ranging from 0.03 to 0.09 microg. kg(-1) . min(-1). A maximum
      mean remifentanil dose of 0.057microg. kg(-1) . min(-1) was reached after 4 h.
      The combination of remifentanil with a nonsteroidal antiinflammatory drug
      provided adequate analgesia in 73% of patients 30 min after tracheal extubation.
      Rapid dose titration was necessary during the first 10 min in 50% of patients.
      Increasing the initial remifentanil dose could shorten the titration period but
      may be associated with respiratory complications.

PMID- 15845660
TI  - Are the incidences of cardiac events during noncardiac surgery in Japan the same
      as in the United States and Europe?
AB  - In Japan, an ever-present problem in the preoperative evaluation of patients with
      ischemic heart disease is that although such evaluations are based on Western
      data, these data serve as the basis for determining perioperative risk in
      Japanese patients. To remedy this problem, the Cardiac Ischemia and Anesthesia
      Research Committee was formed in 1997 and has conducted studies of perioperative
      complications in noncardiac surgery in Japan. In two retrospective studies in
      1997, the proportions of patients with ischemic heart disease were 3.9% and 3.1%,
      approximately one tenth the rates reported in Europe and the United States. The
      incidences of perioperative cardiac complications in patients with ischemic heart
      disease were 16.4% and 13.2%, not widely divergent from rates reported in Europe
      and the United States. To investigate the baseline characteristics involved in
      perioperative complications, we conducted a prospective study of 237 patients
      classified as having intermediate risk for perioperative cardiac complications
      according to the American College of Cardiology/American Heart Association
      Guidelines for Perioperative Cardiovascular Evaluation for Noncardiac Surgery. We
      found that the prominent factor in intraoperative cardiac complications was the
      presence of hypertension (odds ratio = 2.911). Factors contributing to
      postoperative cardiac complications included those reflecting coronary lesion
      severity and cardiac dysfunction (history of heart failure; odds ratio = 6.884,
      coronary risk index grade; odds ratio = 2.884, and a history of intervention;
      odds ratio = 4.774).

PMID- 15845661
TI  - Perioperative and long-term morbidity and mortality after above-knee and below
      knee amputations in diabetics and nondiabetics.
AB  - We performed a retrospective review of a vascular surgery quality assurance
      database to evaluate the perioperative and long-term morbidity and mortality of
      above-knee amputations (AKA, n = 234) and below-knee amputations (BKA, n = 720)
      and to examine the effect of diabetes mellitus (DM) (181 of AKA and 606 of BKA
      patients). All patients in the database who had AKA or BKA from 1990 to May 2001
      were included in the study. Perioperative 30-day cardiac morbidity and mortality
      and 3-yr and 10-yr mortality after AKA or BKA were assessed. The effect of DM on
      30-day cardiac outcome was assessed by multivariate logistic regression and the
      effect on long-term survival was assessed by Cox regression analysis. The
      perioperative cardiac event rate (cardiac death or nonfatal myocardial
      infarction) was at least 6.8% after AKA and at most 3.6% after BKA. Median
      survival was significantly less after AKA (20 mo) than BKA (52 mo) (P < 0.001).
      DM was not a significant predictor of perioperative 30-day mortality (odds ratio,
      0.76 [0.39-1.49]; P = 0.43) or 3-yr survival (Hazard ratio, 1.03 [0.86-1.24]; P =
      0.72) but predicted 10-yr mortality (Hazard ratio, 1.34 [1.04-1.73]; P = 0.026).
      Significant predictors of the 30-day perioperative mortality were the site of
      amputation (odds ratio, 4.35 [2.56-7.14]; P < 0.001) and history of renal
      insufficiency (odds ratio, 2.15 [1.13-4.08]; P = 0.019). AKA should be triaged as
      a high-risk surgery while BKA is an intermediate-risk surgery. Long-term survival
      after AKA or BKA is poor, regardless of the presence of DM.

PMID- 15845662
TI  - A review of aprotinin in orthotopic liver transplantation: can its harmful
      effects offset its beneficial effects?
AB  - Blood transfusion can adversely affect patient outcome and graft survival in
      orthotopic liver transplantation (OLT). With this respect, prophylactic aprotinin
      administration decreases blood loss, transfusion requirements, and the
      hemodynamic changes associated with graft reperfusion in patients undergoing OLT.
      However, data indicate limiting the use of aprotinin in OLT: (a) clinical,
      biological, echocardiographic, and postmortem findings recorded in patients with
      chronic liver disease or undergoing OLT suggest that a continuous prothrombotic
      state exists in these patients. Whether the inhibition of fibrinolysis associated
      with aprotinin therapy will expose some patients to untoward thrombosis is
      questionable; (b) aprotinin does not appear to alter postoperative outcome in
      patients undergoing OLT; (c) aprotinin decreases blood transfusion requirements
      only when surgery is associated with significant blood loss. However, at the
      present time, median transfusion requirements of 2 to 5 red blood cell units are
      required in OLT.

PMID- 15845663
TI  - A rupture of both atrioventricular valves after blunt chest trauma: the
      usefulness of transesophageal echocardiography for a life-saving diagnosis.
AB  - Survival after the rupture of the both mitral and tricuspid valves in blunt
      thoracic trauma is uncommon and requires prompt diagnosis and treatment. We
      present a case in which transesophageal echocardiography performed in the
      operating room by the anesthesiologist identified the etiology of hemodynamic
      instability and facilitated successful emergency replacement of both valves.

PMID- 15845664
TI  - Phantom aortic valve pressure gradient: discrepancies between cardiac
      catheterization and Doppler echocardiography.
AB  - We present a case of a patient scheduled for mitral valve replacement and
      possible aortic valve replacement. On Doppler examination, her peak transaortic
      pressure gradient measured on three separate occasions (pre-, intra-, and
      postoperatively) was approximately 60 mm Hg. In contrast, the peak-to-peak
      pressure gradient (cardiac catheterization) was 11 mm Hg. This latter gradient
      was confirmed in the operating room by direct simultaneous measurement of the
      pressures in the left ventricle and ascending aorta. Potential causes for this
      discrepancy are discussed, among which the "pressure recovery phenomenon" is
      considered the most important.

PMID- 15845665
TI  - The surgical patient with Brugada syndrome: a four-case clinical experience.
AB  - Brugada syndrome is characterized by a distinctive electrocardiographic pattern
      (right bundle branch block and ST segment elevation in precordial leads) and a
      high risk of cardiac arrest for malignant dysrhythmia. The genetic basis is a
      molecular defect of the cardiac sodium channel and the pattern of inheritance is
      autosomal dominant. Many factors during general anesthesia (medications,
      bradycardia, temperature changes) could precipitate malignant dysrhythmia in
      these patients. Because criteria to identify the surgical patient at high risk
      for developing malignant dysrhythmia are lacking, we can only speculate about the
      available studies on nonsurgical patients. We describe four patients during
      general anesthesia and propose intraoperative and postoperative monitoring (the
      first 36 h).

PMID- 15845666
TI  - Unusual presentation of postcardiotomy hemorrhage in an infant with congenital
      heart disease.

PMID- 15845667
TI  - Persistent left superior vena cava in a patient with a history of tetralogy of
      Fallot.

PMID- 15845668
TI  - Cost-effectiveness of routine intraoperative transesophageal echocardiography in
      pediatric cardiac surgery: a 10-year experience.
AB  - The beneficial effect of transesophageal echocardiography (TEE) on medical and
      surgical treatment of children with congenital heart disease has been
      established. Its cost-effectiveness, however, has not been extensively studied.
      We analyzed reports of 580 routine TEE examinations performed in our institution
      between January 1994 and December 2003 in patients younger than 17 yr who
      required congenital cardiac surgery. After excluding patients who died
      immediately postoperatively, we identified 33 patients (5.7%) who required a
      second bypass run on clear-cut indication, i.e., surgical reoperation, and who
      clearly benefited from TEE findings. An estimate of both fixed and variable costs
      revealed a savings of 850 to 2655 Swiss francs (CHF) ($690 to $2130 US) per
      child. This figure undoubtedly underestimates the true cost-effectiveness of
      routine intraoperative TEE in this setting because we used mostly conservative
      estimates of the benefits and liberal estimates of the costs. The potential
      benefits of TEE in hemodynamic monitoring and medical management, in reduction of
      postoperative morbidity, and in improvement in the quality of life are intangible
      and were not considered. Although benefits and costs vary according to market
      conditions, patient populations, surgical practice, and technical expertise with
      TEE, our analysis demonstrates substantial cost-effectiveness in the use of
      routine TEE during pediatric cardiac surgery.

PMID- 15845669
TI  - An evaluation of the effects of a standard heparin dose on thrombin inhibition
      during cardiopulmonary bypass in neonates.
AB  - We compared the adequacy of heparinization in neonates and older children
      undergoing cardiopulmonary bypass (CPB) by measuring heparin activity, thrombin
      formation, and thrombin activity. Ten neonates and 10 older children were
      administered 400 U/kg of heparin before CPB. Heparin anti-Xa activity,
      prothrombin fragment 1.2 (F1.2), and fibrinopeptide A (FPA) were measured at
      baseline, after 30 min on CPB, immediately post-CPB, and 3 and 24 h post-CPB.
      Heparin anti-Xa activity was significantly decreased during and immediately post
      CPB in the neonatal group. F1.2 and FPA levels in neonates were significantly
      higher at baseline, decreased with the commencement of CPB, and increased to
      levels higher than those in older children after CPB. Our data show that with
      standard heparin doses, neonates exhibit less heparin anti-Xa activity during
      CPB. Higher baseline levels of F1.2 and FPA present in neonates indicate
      preoperative activation of their coagulation systems as compared with older
      children. Although F1.2 and FPA levels initially decrease with the commencement
      of CPB, probably representing hemodilution, the subsequent increase in these
      markers indicates significantly more thrombin formation and activity during and
      after CPB. These results raise the concern that 400 U/kg of heparin may not
      adequately suppress thrombin formation and activity in neonates undergoing CPB.

PMID- 15845670
TI  - Postoperative analgesia after spinal blockade in infants and children undergoing
      cardiac surgery.
AB  - The aim of this prospective, randomized, controlled clinical trial was to define
      the opioid analgesic requirement after a remifentanil (REMI)-based anesthetic
      with spinal anesthetic blockade (SAB+REMI) or without (REMI) spinal blockade for
      open-heart surgery in children. We enrolled 45 patients who were candidates for
      tracheal extubation in the operating room after cardiac surgery. Exclusion
      criteria included age <3 mo and >6 yr, pulmonary hypertension, congestive heart
      failure, contraindication to SAB, and failure to obtain informed consent. All
      patients had an inhaled induction with sevoflurane and maintenance of anesthesia
      with REMI and isoflurane (0.3% end-tidal). In addition, patients assigned to the
      SAB+REMI group received SAB with tetracaine (0.5-2.0 mg/kg) and morphine (7
      mug/kg). After tracheal extubation in the operating room, patients received
      fentanyl 0.3 mug/kg IV every 10 min by patient-controlled analgesia for pain
      score = 4. Pain scores and fentanyl doses were recorded every hour for 24 h or
      until the patient was ready for discharge from the intensive care unit. Patients
      in the SAB+REMI group had significantly lower pain scores (P = 0.046 for the
      first 8 h; P =0.05 for 24 h) and received less IV fentanyl (P = 0.003 for the
      first 8 h; P = 0.004 for 24 h) than those in the REMI group. There were no
      intergroup differences in adverse effects, including hypotension, bradycardia,
      highest PaCO(2), lowest pH, episodes of oxygen desaturation, pruritus, and
      vomiting.

PMID- 15845671
TI  - A comparison of the Vasotrac with invasive arterial blood pressure monitoring in
      children after pediatric cardiac surgery.
AB  - The Vasotrac is a device that provides near-continuous and noninvasive arterial
      blood pressure monitoring and may be an alternative to direct intraarterial
      measurement. It has been evaluated in adult patients, but minimal information is
      available for pediatric patients. We evaluated agreement between measurements of
      arterial blood pressure and heart rate obtained from the Vasotrac versus an
      arterial catheter in a pediatric population. Children undergoing corrective
      cardiac surgery were enrolled. Simultaneous arterial blood pressure measurements
      were obtained postoperatively from the Vasotrac unit and an arterial catheter.
      Bland-Altman plots were constructed to assess agreement. Paired correlation
      analysis, bias, and precision calculations were performed. Sixteen patients, mean
      age 10.1 +/- 2.3 yr and weight 34.6 +/- 11.9 kg, were enrolled. Four-thousand-one
      hundred- two paired measurements were obtained. Arterial blood pressures
      measured noninvasively correlated with catheter measurements with Pearson r
      values of 0.90, 0.80, and 0.91 for systolic, diastolic, and mean arterial blood
      pressures, respectively (all P < 0.001). There was excellent agreement between
      arterial blood pressure measurement methods. Absolute mean differences based on
      mixed-model regression with 95% confidence intervals were 4.0 mm Hg (3.0-5.0 mm
      Hg), 4.3 mm Hg (3.1-5.5 mm Hg), and 3.5 mm Hg (2.5-4.0 mm Hg) for systolic blood
      pressure, diastolic blood pressure, and mean blood pressure, respectively.
      Arterial blood pressure measurements obtained from the Vasotrac agreed well with
      invasive arterial monitoring in pediatric patients.

PMID- 15845672
TI  - Dexmedetomidine exerts dose-dependent age-independent antinociception but age
      dependent hypnosis in Fischer rats.
AB  - Dexmedetomidine (Dex), an alpha(2)-adrenoceptor agonist, is an effective
      analgesic and sedative drug in adults; however, little information is available
      about its efficacy in pediatric populations. Some anesthetics exhibit an age
      dependent analgesic effect, e.g., nitrous oxide, being relatively ineffective in
      newborn rats. We investigated the analgesic and hypnotic efficacy of Dex using 6
      cohorts of Fischer rats aged 7, 15, 19, 23, and 29 days and adults exposed to
      either Dex (10 or 50 microg/kg) or saline subcutaneously. Formalin plantar
      testing was used to mimic inflammatory pain, and its effect was assessed using
      immunohistochemical (c-Fos staining) and behavioral methods. The hypnotic action
      of Dex was assessed by loss of righting reflex. Formalin administration produced
      a typical nociceptive response in each age group; these nociceptive responses
      were significantly attenuated by Dex 50 microg/kg at all ages (P < 0.05), whereas
      Dex 10 microg/kg had little effect. Neonatal rats showed the greatest hypnotic
      sensitivity to Dex (P < 0.05).

PMID- 15845673
TI  - Accuracy in the alteration of acetaminophen suppositories.
AB  - Many pediatric anesthesiologists divide acetaminophen suppositories to achieve an
      approximate dose. In this three-part study we first surveyed pediatric
      anesthesiologists regarding their attitudes and frequency of this clinical
      practice. Second, acetaminophen suppositories were divided for analysis of
      acetaminophen content. Finally, the accuracy of pediatric anesthesiologists in
      dividing suppositories was assessed. The survey indicated 50% of
      anesthesiologists believed acetaminophen was nonuniform and 62% believed the
      alteration of suppositories was inaccurate. The laboratory investigation revealed
      uniform distribution of acetaminophen but poor accuracy in achieving the target
      dose. The findings suggest using only intact suppositories for improved accuracy.

PMID- 15845674
TI  - Changing role of COX-2 inhibitors in the perioperative period: is parecoxib
      really the answer?

PMID- 15845675
TI  - A randomized, double-blind comparison between parecoxib sodium and propacetamol
      for parenteral postoperative analgesia after inguinal hernia repair in adult
      patients.
AB  - The newly injectable cyclooxygenase-2 selective nonsteroidal antiinflammatory
      drug, parecoxib, has never been compared with propacetamol, a parenteral
      formulation of acetaminophen. In this prospective, randomized, double-blind,
      double-dummy study, we randomly assigned 182 patients scheduled for initial
      inguinal hernia repair under general anesthesia to receive a single injection of
      40 mg parecoxib or 2 injections of 2 g propacetamol within the first 12 h after
      surgery. The study variables were morphine consumption, pain at rest and while
      coughing, and patient satisfaction throughout the first 12 h postoperatively. For
      statistical analysis, we used the Student's t-test, chi(2), and covariance
      analysis. Total morphine consumption did not differ between the two groups. Pain
      was less intense in the parecoxib group at rest (P = 0.035) but did not differ
      for pain while coughing. The incidence of side effects was similar. Significantly
      more patients in the parecoxib group rated their pain management as good or
      excellent (87% versus 70% in the propacetamol group, P = 0.001). Within the first
      12 h after inguinal hernia repair in adult patients, a single injection of
      parecoxib 40 mg compares favorably with 2 injections of propacetamol 2 g.

PMID- 15845676
TI  - Music and ambient operating room noise in patients undergoing spinal anesthesia.
AB  - Previous studies have indicated that music decreases intraoperative sedative
      requirements in patients undergoing surgical procedures under regional
      anesthesia. In this study we sought to determine whether this decrease in
      sedative requirements results from music or from eliminating operating room (OR)
      noise. A secondary aim of the study was to examine the relationship of response
      to intraoperative music and participants' culture (i.e., American versus
      Lebanese). Eighty adults (36 American and 54 Lebanese) undergoing urological
      procedures with spinal anesthesia and patient-controlled IV propofol sedation
      were randomly assigned to intraoperative music, white noise, or OR noise. We
      found that, controlling for ambient OR noise, intraoperative music decreases
      propofol requirements (0.004 +/- 0.002 mg . kg(-1) . min(-1) versus 0.014 +/-
      0.004 mg . kg(-1) . min(-1) versus 0.012 +/- 0.002 mg . kg(-1) . min(-1); P =
      0.026). We also found that, regardless of group assignment, Lebanese patients
      used less propofol as compared with American patients (0.005 +/- 0.001 mg . kg(
      1) . min(-1) versus 0.017 +/- 0.003 mg . kg(-1) . min(-1); P = 0.001) and that,
      in both sites, patients in the music group required less propofol (P < 0.05). We
      conclude that when controlling for ambient OR noise, intraoperative music
      decreases propofol requirements of both Lebanese and American patients who
      undergo urological surgery under spinal anesthesia.

PMID- 15845677
TI  - Cerebrospinal fluid and plasma pharmacokinetics of the cyclooxygenase 2 inhibitor
      rofecoxib in humans: single and multiple oral drug administration.
AB  - Cerebrospinal fluid (CSF) pharmacokinetics of orally administered cyclooxygenase
      2 inhibitors, with single or multiple dosing, is of clinical relevance because it
      may relate to the analgesic efficacy of these drugs. We enrolled 9 subjects with
      implanted intrathecal catheters in the study. After 50-mg oral rofecoxib
      administration, the CSF drug concentration lagged slightly behind the plasma drug
      concentration. The ratio of the 24-h area under the drug-concentration curve
      (AUC) in CSF to plasma was 0.142. After daily dosing of rofecoxib 50 mg/d for 9
      days, rofecoxib concentrations in plasma and CSF were larger on Day 9 than on Day
      1, with the 24-h AUC on Day 9 more than twice the Day 1 AUC for both plasma and
      CSF. After nine consecutive daily doses of rofecoxib, the AUC(CSF)/AUC(plasma)
      ratio was 0.159. The important findings of this study are that CSF rofecoxib
      levels are approximately 15% of plasma levels and that repeated daily dosing more
      than doubles the AUC in CSF.

PMID- 15845678
TI  - The concentration-dependent effects of general anesthesia on spontaneous
      baroreflex indices and their correlations with pharmacological gains.
AB  - Beat-to-beat assessment of spontaneously occurring fluctuations in heart rate and
      arterial blood pressure allows noninvasive determination of cardiovagal function,
      but little is known regarding the effects of general anesthesia on spontaneous
      baroreflex (SBR) indices. We examined (a) concentration-dependent effects of
      sevoflurane on SBR indices, heart rate variability (HRV), and blood pressure
      variability and (b) correlation and agreement between pharmacological baroreflex
      gains and SBR indices during sevoflurane anesthesia. Continuous electrocardiogram
      and invasive arterial blood pressure were monitored in nine healthy volunteers
      before, during, and for 3 h after sevoflurane anesthesia, during which end-tidal
      sevoflurane was maintained at 0.7%, 1.4%, and 2.0% in random sequences. We
      derived three SBR indices (sequence method, alpha-index, and low-frequency
      transfer function) and compared them with pressor and depressor test gains by the
      pharmacological method. HRV and blood pressure variability were analyzed at a
      fixed respiratory rate (12 breaths/min) in awake and anesthetized conditions.
      Except for low-frequency transfer function, SBR indices were depressed by
      sevoflurane and remained depressed for 30 min after emergence from anesthesia,
      compared with the conscious baseline value. Spontaneous sequence indices and high
      and low-frequency powers of HRV demonstrated concentration-dependent depression.
      Pharmacological gains and SBR indices during anesthesia generally correlated
      well, but Bland-Altman analysis revealed that SBR indices had limits of agreement
      as large as the baroreflex gain itself. These data suggest that spontaneous
      indices are inadequate estimates of, and are inconsistent with, the
      pharmacological baroreflex gain during sevoflurane anesthesia.

PMID- 15845679
TI  - Administration of epinephrine does not increase learning of fear to tone in rats
      anesthetized with isoflurane or desflurane.
AB  - Previous reports suggest that the administration of epinephrine increases
      learning during deep barbiturate-chloral hydrate anesthesia in rats but not
      during anesthesia with 0.4% isoflurane in rabbits. We revisited this issue, using
      fear conditioning to a tone in rats as our experimental model for learning and
      memory and isoflurane and desflurane as our anesthetics. Expressed as a fraction
      of the minimum alveolar anesthetic concentration (MAC) preventing movement in 50%
      of rats, the amnestic 50% effective dose (ED(50)) for fear to tone in control
      rats inhaling isoflurane and injected with saline intraperitoneally (i.p.) was
      0.32 +/- 0.03 MAC (mean +/- se) compared with 0.37 +/- 0.06 MAC in rats injected
      with 0.01 mg/kg of epinephrine i.p. and 0.38 +/- 0.03 MAC in rats injected with
      0.1 mg/kg of epinephrine i.p. For desflurane, the amnestic ED(50) were 0.32 +/-
      0.05 MAC in control rats receiving a saline injection i.p. versus 0.36 +/- 0.04
      MAC in rats injected with 0.1 mg/kg of epinephrine i.p. We conclude that
      exogenous epinephrine does not decrease amnesia produced by inhaled isoflurane or
      desflurane, as assessed by fear conditioning to a tone in rats.

PMID- 15845680
TI  - A comparison of target- and manually controlled infusion propofol and
      etomidate/desflurane anesthesia in elderly patients undergoing hip fracture
      surgery.
AB  - Elderly patients have a higher risk of developing adverse drug reactions during
      anesthesia, especially anesthesia affecting cardiovascular performance. In this
      prospective randomized study we compared quality of induction, hemodynamics, and
      recovery in elderly patients scheduled for hip fracture surgery and receiving
      either etomidate/desflurane (ETO/DES) or target-controlled (TCI) or manually
      controlled (MAN) propofol infusion for anesthesia. Sixteen patients were
      anesthetized with ETO (0.4 mg/kg) followed by DES titrated from an initial end
      tidal concentration of 2.5%. Eighteen patients received propofol TCI at an
      initial plasma concentration of 1 microg/mL and titrated upwards by 0.5-microg/mL
      steps. Fifteen patients received a bolus induction of propofol 1 mg/kg over 60 s
      followed by an infusion initially set at 5 mg . kg(-1) . h(-1). All received a
      bolus (20 microg/kg) followed by an infusion of 0.4 microg . kg(-1) . min(-1)
      alfentanil. According to hemodynamics, concentrations of DES or propofol (TCI
      group) and propofol infusion rate (MAN group) were respectively adjusted by a
      step of 20% and 50%. In the TCI and ETO/DES groups, the time spent at a mean
      arterial blood pressure within 15% and 30% of baseline values was more than 60%
      and 80% of anesthesia time, whereas in the MAN group it was <30% and 60%,
      respectively. In the MAN group more anesthetic drug adjustments were recorded
      (6.4 +/- 2.8 versus 2.5 +/- 1.2 [ETO/DES] and 2.6 +/- 1 [TCI]). TCI improves the
      time course of propofol's hemodynamic effects in elderly patients.

PMID- 15845681
TI  - The effect of nitrous oxide on the dose-response relationship of rocuronium.
AB  - It has been generally assumed that nitrous oxide (N(2)O) enhances the effects of
      nondepolarizing muscle relaxants only weakly if at all. More recent evidence
      suggests that drug potency may be more intense under N(2)O anesthesia compared
      with total IV anesthesia (TIVA). However, the magnitude of this effect has not
      been well defined. We measured the 50% effective dose of rocuronium in 35
      patients receiving N(2)O-propofol-opioid anesthesia and a comparable group
      receiving TIVA. A single dose of rocuronium was given to each patient and drug
      potency was calculated for each individual from the Hill equation assuming a log
      dose/logit slope of 4.5. In both groups, the relaxant was administered 15 min
      after induction of anesthesia. Neuromuscular function was measured using
      electromyography with single stimuli at 0.10 Hz. We measured a 50% effective dose
      of 0.209 +/- 0.051 mg/kg during TIVA and of 0.166 +/- 0.041 mg/kg during N(2)O
      anesthesia, a decrease of 20% (P < 0.001). The clinical importance of this effect
      must be considered modest; however, estimates of potency that are usually
      obtained during N(2)O anesthesia may underestimate drug requirements at the time
      of induction of anesthesia.

PMID- 15845682
TI  - The quantitative distinction between train-of-four "counts of 2" and posttetanic
      "counts of 2" evidenced by a stable paralysis/stable infusion rate method in
      anesthetized patients receiving mivacurium.
AB  - In this study we quantitatively evaluated, by a stable paralysis/stable infusion
      rate method, the difference between two standardized paralysis levels--train-of
      four (TOF) count of 2 responses and posttetanic count (PTC) of 2. Ten ASA
      physical status I-II consenting adult patients scheduled for elective surgery
      were anesthetized (sufentanil/propofol), tracheally intubated, mechanically
      normoventilated with a fixed O(2)/air mixture, and normothermic; oropharynx and
      thenar temperatures were maintained above 36 degrees and 32.5 degrees C,
      respectively. After partial recovery from 200 microg/kg mivacurium (MIV), stable
      tactile TOF and PTC counts of 2 paralysis levels were induced on the adductor
      pollicis muscle by manual adjustments of an infusion pump containing MIV. The
      paralysis levels and the infusion rates were considered as stable once they
      remained constant at 4 consecutive time points separated by 5 min each. Infusion
      rates observed were: TOF count 2-6 (2-11) and PTC 2-17 (3-18) microg . kg(-1) .
      min(-1) (P < 0.001; Wilcoxon's paired comparison test). Under the present
      conditions, obtaining and maintaining a PTC of 2 requires MIV infusion rates far
      in excess of the "standard" recommendations mentioned in the literature for MIV
      infusion management.

PMID- 15845683
TI  - The effect of erythromycin and fluvoxamine on the pharmacokinetics of intravenous
      lidocaine.
AB  - Inhibitors of CYP3A4 (cytochrome P450 3A4) have a minor effect on lidocaine
      pharmacokinetics. We studied the effect of coadministration of the antidepressant
      fluvoxamine (CYP1A2 inhibitor) and antimicrobial drug erythromycin (CYP3A4
      inhibitor) on lidocaine pharmacokinetics in a double-blind, randomized, three-way
      crossover study. Nine volunteers ingested daily 100 mg fluvoxamine and placebo,
      100 mg fluvoxamine and 1500 mg erythromycin, or their corresponding placebos for
      5 days. On day 6, 1.5 mg/kg lidocaine was administered IV over 60 min.
      Concentrations of lidocaine and its major metabolite monoethylglycinexylidide
      were measured for 10 h. Fluvoxamine alone decreased the clearance of lidocaine by
      41% (P < 0.001) and prolonged its elimination half-life from 2.6 to 3.5 h (P <
      0.01). During the combination of fluvoxamine and erythromycin, lidocaine
      clearance was 53% smaller than during placebo (P < 0.001) and 21% smaller than
      during fluvoxamine alone (P < 0.05). During the combination phase the half-life
      of lidocaine (4.3 h) was longer than during the placebo (2.6 h; P < 0.001) or
      fluvoxamine (3.5 h; P < 0.01). We conclude that inhibition of CYP1A2 by
      fluvoxamine considerably reduces elimination of lidocaine and may increase the
      risk of lidocaine toxicity. Concomitant use of both fluvoxamine and a CYP3A4
      inhibitor such as erythromycin can further increase plasma lidocaine
      concentrations by decreasing its clearance.

PMID- 15845684
TI  - Desflurane, malignant hyperthermia, and release of compartment syndrome.
AB  - We describe a case of suspected malignant hyperthermia in a healthy 20-yr-old
      man. The patient underwent urgent release of upper extremity compartment syndrome
      as a result of traumatic vascular injury. After 3 h of general anesthesia with
      desflurane, he developed a hypermetabolic state (hypercarbia, hyperthermia,
      hyperkalemia, and metabolic acidosis), consistent with the diagnosis of malignant
      hyperthermia. Cardiovascular instability coincided with reperfusion of the
      injured extremity. Treatment with dantrolene and supporting measures restored
      cardiovascular stability. Three days later he underwent a successful second
      surgery under regional block with total IV anesthesia.

PMID- 15845685
TI  - Patent medicine and the "black box".

PMID- 15845686
TI  - A case of awareness despite an "adequate depth of anesthesia" as indicated by a
      Bispectral Index monitor.
AB  - We report a case of awareness that occurred despite the presence of an "adequate"
      depth of anesthesia as measured by Bispectral Index. Our patient was at high risk
      for this complication. Hypotension limited the use of sevoflurane, and
      neuromuscular, sympathetic, and beta-adrenergic blockade prevented the patient
      from responding to his awareness. Preoperative use of opioids and gabapentin for
      chronic pain may have modified his response to anesthesia or affected his
      Bispectral Index reading. Our attempt to measure depth of anesthesia may have
      resulted in false reassurance concerning adequacy of anesthesia and contributed
      to awareness.

PMID- 15845687
TI  - Electroencephalogram monitoring during anesthesia with propofol and alfentanil:
      the impact of second order spectral analysis.
AB  - Bispectral analysis of the electroencephalogram (EEG) has been used for
      monitoring anesthesia. The estimation of bicoherence allows us to determine
      whether a given time series represents a linear random process in cases where the
      bicoherence is trivial, i.e., a mere constant independent of frequency. In this
      study, we investigated the proportion of EEG epochs with nontrivial bicoherence
      during surgical anesthesia with propofol and alfentanil as an indicator for the
      degree of nonlinearity in the EEG. We reanalyzed 90 h of EEG recorded from 20
      patients undergoing abdominal surgery using the Hinich procedure, which provides
      a statistical test for the following hypothesis: the EEG is a linear random
      process. In approximately 90% of all artifact-free, stationary EEG epochs, the
      bicoherence was found to be zero or a mere constant. Under these conditions, the
      EEG can be considered as a linear random process. Our findings suggest that the
      spectral information in the frequency domain delivered by the EEG monitoring
      during anesthesia is largely contained in the power spectrum of the signal. This
      calls into question the benefit of EEG bispectral analysis for monitoring
      anesthesia effect.

PMID- 15845688
TI  - Changes in the bispectral index during intraabdominal irrigation in patients
      anesthetized with nitrous oxide and sevoflurane.
AB  - Surgical stimulation typically results in an activation of
      electroencephalographic activity. In some instances, painful stimulation in the
      presence of inadequate anesthesia results in a suppression of the
      electroencephalogram. This phenomenon has been referred to as a "paradoxical
      arousal." In our daily practice, we have noted a marked decrease in the
      bispectral index (BIS) with large delta waves during abdominal surgery when the
      abdominal cavity was irrigated with normal saline. In the present study, we
      sought to evaluate changes in BIS during intraabdominal irrigation. Eighteen ASA
      physical status I-II patients scheduled for elective abdominal surgery were
      enrolled in the study and allocated randomly to the control group (group C) or
      the fentanyl group (group F). Anesthesia was induced with 3 mg/kg of thiopental
      and was maintained with sevoflurane and 50% nitrous oxide. BIS, 95% spectral edge
      frequency (SEF95), and burst-suppression ratio were recorded using a BIS monitor.
      Near the end of the procedure, but before irrigation of the abdominal cavity, 1.5
      microg/kg fentanyl was given IV to group F. There was no significant change in
      BIS or SEF95 in group F patients during subsequent irrigation of the abdominal
      cavity. In contrast, BIS and SEF95 decreased significantly after start of
      irrigation in group C patients. These data show that the stimulation occurring
      during intraabdominal irrigation might cause a paradoxical arousal response, as
      evidenced by a decrease in processed electroencephalographic parameters.
      Pretreatment with fentanyl suppressed these changes. Anesthesiologists should be
      aware of this paradoxical arousal response to avoid an inappropriate decrease in
      the anesthetic concentration in such situations.

PMID- 15845689
TI  - A method for measuring the effectiveness of simulation-based team training for
      improving communication skills.
AB  - Team behavior and coordination, particularly communication or team information
      sharing, are critical for optimizing team performance; research in medicine
      generally provides no accepted method for measurement of team information
      sharing. In a controlled simulator setting, we developed a technique for placing
      clinical information (probes) with members of a team of trainees participating in
      a 1-day Anesthesia Crisis Resource Management course and later tested the teams
      for knowledge of the probes as an indicator of overall team information-sharing.
      Despite the low level of team information-sharing, we demonstrated construct
      validity of the probe methodology by the correlation of measured change in team
      information-sharing from beginning to end of training with self-rated change.
      There was no statistical difference in "group sharing" from beginning to end of
      training, despite trainees' survey responses that the course would be useful for
      their education and practice.

PMID- 15845690
TI  - The relationship between cardiac output measured by the thermodilution method and
      that measured by the carbon dioxide rebreathing technique during laparoscopic
      surgery.
AB  - Carbon dioxide insufflation during laparoscopic surgery may interfere with the
      accuracy of the cardiac output value measured by the NICO2 system. The authors
      simultaneously measured cardiac output by the thermodilution method and by the
      carbon dioxide rebreathing technique during laparoscopic adrenalectomy in a
      patient with a nonfunctional adrenal tumor. There was a strong correlation
      between the cardiac output values measured by the two methods. This case report
      suggests that the carbon dioxide rebreathing technique can be used to monitor
      cardiac output during laparoscopic surgery.

PMID- 15845691
TI  - Preincisional dextromethorphan combined with thoracic epidural anesthesia and
      analgesia improves postoperative pain and bowel function in patients undergoing
      colonic surgery.
AB  - Colonic surgery is associated with severe postoperative pain and postoperative
      ileus, which contribute to delayed hospital discharge. In previous studies, we
      demonstrated that IM dextromethorphan (DM) provided preemptive analgesia and
      improved postoperative pain. The benefit of thoracic epidural anesthesia (TEA)
      and postoperative epidural analgesia on postoperative pain was well demonstrated.
      The goal of this study was to investigate the effect of preincisional IM DM
      combined with intraoperative TEA and postoperative patient-controlled epidural
      analgesia (PCEA) on pain and bowel function after colonic surgery. Patients were
      randomized into 3 equal groups to receive: 1) chlorpheniramine maleate (CPM) 20
      mg and general anesthesia (CPM-GA); 2) CPM 20 mg and GA combined with TEA (CPM
      TEA); or 3) DM 40 mg (containing 20 mg of CPM) and GA combined with TEA (DM-TEA).
      The CPM, DM, and TEA with lidocaine were administered after GA induction via an
      IM injection and 30 min before the skin incision. All patients received
      postoperative PCEA for pain control. Analgesic effects were evaluated for 72 h
      after surgery using visual analog scale pain scores at rest and moving, time to
      first PCEA request for pain relief, total PCEA consumption, and the time to first
      passage of flatus. Statistically significant improvement of postoperative pain
      and bowel function was observed in the following order: DM-TEA > CPM-TEA > CPM
      GA. Compared with the CPM-TEA group, the DM-TEA group averaged 1.6 points lower
      on first-hour pain scores, 40 min longer to first PCEA request, 15.8 mL less PCEA
      drug over 72 h, and 14.7 h earlier bowel function (all P < 0.01). We conclude
      that the combination of preincisional DM (40 mg IM), intraoperative TEA, and
      postoperative PCEA enhances analgesia and facilitates recovery of bowel function,
      suggesting possible synergistic interaction with local anesthetics and opioids.

PMID- 15845692
TI  - Preoperative inhibition of cyclooxygenase-1 in the spinal cord reduces
      postoperative pain.
AB  - Intrathecal administration of cyclooxygenase (COX)-1, but not COX-2, specific
      inhibitors given on postoperative day 1 has analgesic effects in an incisional
      model of postoperative pain. We investigated the effects of preoperative
      administration of intrathecal COX inhibitors in this model. Fifteen minutes
      before surgery, rats received intrathecally the COX-1 preferring inhibitor,
      ketorolac, the specific COX-1 inhibitor, SC-560, the COX-2 inhibitor, NS-398, or
      vehicle. A 1-cm longitudinal incision was then made through skin, fascia, and
      muscles of the plantar aspect of a left paw in male rats. Withdrawal threshold to
      von Frey filaments was measured at 2 h, 4 h, and at intervals up to 5 days later.
      Ketorolac and SC-560 increased withdrawal threshold to mechanical stimulation,
      but NS-398 had no significant effect. These results suggest that COX-1 plays an
      important role in spinal cord pain processing and sensitization after surgery and
      that preoperative intrathecal administration of specific COX-1 inhibitors may be
      useful to treat postoperative pain.

PMID- 15845693
TI  - Preoperative gabapentin decreases anxiety and improves early functional recovery
      from knee surgery.
AB  - Gabapentin has antihyperalgesic and anxiolytic properties. We thus tested the
      hypothesis that premedication with gabapentin would decrease preoperative anxiety
      and improve postoperative analgesia and early postoperative knee mobilization in
      patients undergoing arthroscopic anterior cruciate ligament repair under general
      anesthesia. Forty patients were randomly assigned to receive 1200 mg oral
      gabapentin or placebo 1-2 h before surgery; anesthesia was standardized. Patients
      received morphine, 0.1 mg/kg, 30 min before the end of surgery and
      postoperatively via a patient-controlled pump. Pain scores and morphine
      consumption were recorded over 48 h. Degrees of active and passive knee flexion
      and extension were recorded during physiotherapy on days 1 and 2. Preoperative
      anxiety scores were less in the gabapentin than control group (visual analog
      scale scores of 28 +/- 16 mm versus 66 +/- 15 mm, respectively; P < 0.001). The
      gabapentin group required less morphine than the control group (29 +/- 22 mg
      versus 69 +/- 40 mg, respectively; P < 0.001). Visual analog scale pain scores at
      rest and after mobilization were significantly reduced in the gabapentin group.
      First and maximal passive and active knee flexions at 24 and 48 h were
      significantly more extensive in the gabapentin than in the control group. In
      conclusion, premedication with 1200 mg gabapentin improved preoperative
      anxiolysis, postoperative analgesia, and early knee mobilization after
      arthroscopic anterior cruciate ligament repair.

PMID- 15845694
TI  - The effects of tramadol and its metabolite on glycine, gamma-aminobutyric acidA,
      and N-methyl-D-aspartate receptors expressed in Xenopus oocytes.
AB  - We assessed the effects of tramadol, a centrally acting analgesic, and its major
      metabolite, on neurotransmitter-gated ion channels. Tramadol binds to mu-opioid
      receptors with low affinity and inhibits reuptake of monoamines in the central
      nervous system. These actions are believed to primarily contribute to its
      antinociceptive effects. However, little is known about other sites of tramadol's
      action. We tested the effects of tramadol and its M1 metabolite (0.1-100 microM)
      on human recombinant neurotransmitter-gated ion channels, including glycine,
      gamma-aminobutyric acid(A) (GABA(A)), and N-methyl-D-aspartate (NMDA) receptors,
      expressed in Xenopus oocytes. Tramadol and M1 metabolite did not have any effects
      on glycine receptors. GABA(A) receptors were significantly inhibited only at
      large concentrations (100 microM). NMDA receptors were inhibited in a
      concentration-dependent manner. Tramadol and M1 metabolite inhibited the
      glutamate-concentration response curve without changing the half-maximal
      effective concentration or the Hill coefficient, indicating a noncompetitive
      inhibition. This study suggests that glycine receptors do not provide the
      antinociceptive effect of tramadol and that the inhibition of GABA(A) receptors
      at large concentration might correlate with convulsions. The inhibitory effect on
      NMDA receptors may contribute to the antinociceptive effect of tramadol at
      relatively large concentrations.

PMID- 15845695
TI  - The monoamine-mediated antiallodynic effects of intrathecally administered
      milnacipran, a serotonin noradrenaline reuptake inhibitor, in a rat model of
      neuropathic pain.
AB  - Antidepressants are often used to treat neuropathic pain. In the present study,
      we determined the antiallodynic effects of selective monoamine reuptake
      inhibitors in the spinal cord in a rat model of neuropathic pain. Mechanical
      allodynia was produced by tight ligation of the left L5 and L6 spinal nerves and
      determined by applying von Frey filaments to the left hindpaw. A serotonin
      noradrenaline reuptake inhibitor, milnacipran, a selective serotonin reuptake
      inhibitor, paroxetine, or a selective noradrenaline reuptake inhibitor,
      maprotiline, was administered intrathecally via a chronically implanted catheter.
      Milnacipran produced dose-dependent antiallodynic effects at doses between 3
      microg and 100 microg. The effect lasted for 7 h after injection of 100 microg (P
      < 0.05). The antiallodynic effect of 30 microg of milnacipran was attenuated by
      intrathecal coadministration of 30 microg of yohimbine, an alpha(2)-adrenoceptor
      antagonist, 30 microg of methysergide, a serotonin receptor antagonist, or 30
      microg of atropine, a muscarinic receptor antagonist (P < 0.01, respectively).
      Intraperitoneal administration of milnacipran had no antiallodynic effects at
      doses of 3 to 30 mg/kg. Antiallodynic effects were not produced by intrathecal
      administration of paroxetine (10 to 100 microg) or maprotiline (10 to 100
      microg). These findings suggest that simultaneous inhibition of serotonin and
      noradrenaline reuptake in the spinal cord is essential to mediate antiallodynic
      effects. Milnacipran might be effective for suppression of neuropathic pain.

PMID- 15845696
TI  - Prolonged differential wound hyperalgesia after an interval of unilateral
      epidural blockade during lower abdominal surgery.
AB  - We assessed postoperative pain at rest and with movement along with wound
      hyperalgesia in a patient who had undergone lower abdominal surgery under general
      anesthesia with a unilateral epidural block that persisted throughout surgery and
      in whom the epidural catheter was replaced immediately afterward. Pain and wound
      hyperalgesia were consistently greater on the "unblocked" side for the 3-wk
      period of observation. Thus, even imperfect intraoperative attenuation of noxious
      stimuli can lead to persistent reductions in postoperative pain.

PMID- 15845697
TI  - Painful traumatic neuroma after a finger stick.
AB  - In this case report we present a patient with a painful traumatic neuroma after a
      finger stick by lancet. The patient benefited from surgical excision of the
      lesion, and her symptoms were completely abolished with additional sympathetic
      nerve blocks.

PMID- 15845698
TI  - Perioperative blood transfusions and delayed wound healing after hip replacement
      surgery: effects on duration of hospitalization.
AB  - Patients who receive allogeneic blood transfusions after orthopedic surgery have
      a longer duration of hospitalization, and this cannot be explained by a more
      frequent incidence of infections in transfused patients. To determine whether
      transfusion of allogeneic blood interferes with wound healing and therefore
      increases the duration of hospitalization, we performed an observational study in
      444 consecutive patients scheduled for elective primary hip surgery. Transfusion,
      wound, and infection variables were collected at five time points during
      treatment. Of the 444 consecutive patients studied, 92 received blood
      transfusions during their perioperative course. Thirty-one percent of transfused
      patients developed wound-healing disturbances versus 18% of the nontransfused
      group (P < 0.05); allogeneic blood transfusion was the only significant predictor
      for development of minor wound-healing disturbances. Duration of hospitalization
      was prolonged in transfused patients (12.3 versus 9.8 days) and could be
      predicted by 4 significant variables: requirement for blood transfusion (adds 2.7
      +/- 0.5 days), presence of wound-healing disturbances (adds 1.3 +/- 0.5 days),
      duration of surgery (adds 0.2 +/- 0.1 days/10 min), and patient's age (adds 0.9
      +/- 0.2 days/10 yr). These data suggest that allogeneic blood transfusion is
      associated with an increased incidence of wound-healing disturbances and that
      prevention of allogeneic blood transfusion may be relevant in limiting the
      duration of admission after elective orthopedic surgery.

PMID- 15845699
TI  - Intravenous or inhaled induction of anesthesia in adults? An audit of
      preoperative patient preferences.
AB  - If given a choice, would patients prefer an inhaled or IV method of inducing
      anesthesia? We investigated the choice between inhaled and IV induction of
      anesthesia of adult patients presenting to an academic institution for ambulatory
      surgery. Of 240 patients audited at the preoperative visit, 212 (88%) reported
      anesthetic histories in which anesthesia had been induced IV and by inhalation in
      203 (96%) and 5 (2%) patients, respectively, with the remaining 4 (2%) having no
      recall of route of the induction of anesthesia. Seventy-eight (33%) patients
      selected IV induction, 120 (50%) chose inhaled induction, and 42 (17%) patients
      were undecided. Sevoflurane was used successfully for induction in 154 patients
      to whom it was offered. These findings seem to contradict the concept that most
      adult patients have an aversion to anesthesia masks and suggest that a fear of
      needle stick may be more prevalent among some populations of American adults.
      Where manpower and facilities permit and in the absence of risk of regurgitation
      or airway difficulty, it is suggested that enquiry be made of healthy adults
      presenting for elective ambulatory surgery as to their preferred route for the
      induction of anesthesia.

PMID- 15845700
TI  - Tactical decision making for selective expansion of operating room resources
      incorporating financial criteria and uncertainty in subspecialties' future
      workloads.
AB  - We considered the allocation of operating room (OR) time at facilities where the
      strategic decision had been made to increase the number of ORs. Allocation occurs
      in two stages: a long-term tactical stage followed by short-term operational
      stage. Tactical decisions, approximately 1 yr in advance, determine what
      specialized equipment and expertise will be needed. Tactical decisions are based
      on estimates of future OR workload for each subspecialty or surgeon. We show that
      groups of surgeons can be excluded from consideration at this tactical stage
      (e.g., surgeons who need intensive care beds or those with below average
      contribution margins per OR hour). Lower and upper limits are estimated for the
      future demand of OR time by the remaining surgeons. Thus, initial OR allocations
      can be accomplished with only partial information on future OR workload. Once the
      new ORs open, operational decision-making based on OR efficiency is used to fill
      the OR time and adjust staffing. Surgeons who were not allocated additional time
      at the tactical stage are provided increased OR time through operational
      adjustments based on their actual workload. In a case study from a tertiary
      hospital, future demand estimates were needed for only 15% of surgeons,
      illustrating the practicality of these methods for use in tactical OR allocation
      decisions.

PMID- 15845701
TI  - A pilot trial evaluating the clinical effects of prolonged storage of red cells.
AB  - The clinical consequences of prolonged storage of red cells have not been
      established. In this pilot study, we evaluated whether it would be feasible to
      provide a continuous supply of red cells stored <8 days. In addition, we examined
      the potential benefits attributed to "fresh" as compared to standard red cells in
      66 critically ill and cardiac surgical patients. Nine patients were issued red
      cells but were not transfused. From the 57 remaining patients, the number of
      units transfused averaged 5.5 +/- 8.43 red cell units in the experimental group
      compared to 3.3 +/- 3.27 red cell units in the standard group (P = 0.25). The
      median storage time was 4 days in the experimental group compared to 19 days in
      the standard group (difference of 15 days; interquartile range of 12-16 days; P <
      0.001). Overall, 73% of patients received red cells with storage times that
      corresponded to the treatment allocation more than 90% of the time. The group
      receiving red cells <8 days old tended to be older on average (68 +/- 8.54 yr
      versus 63 +/- 15.30 yr; P = 0.13) and have more comorbid illnesses (85% versus
      65%; P = 0.09). In total, 27% of patients in the experimental group died or had a
      life-threatening complication as compared to 13% in the standard group (P =
      0.31). There were no differences in prolonged respiratory, cardiovascular, or
      renal support after randomization (P > 0.05). A large clinical trial comparing
      red cell storage times is feasible and warranted given the limited available
      evidence.

PMID- 15845702
TI  - Cannot intubate-cannot ventilate and difficult intubation strategies: results of
      a Canadian national survey.
AB  - The purpose of this study was to determine the preferences of Canadian
      anesthesiologists in difficult intubation and cannot intubate-cannot ventilate
      (CICV) situations. Using a mailed survey, we asked anesthesiologists their
      preferences for and comfort level in using (a) alternative airway devices in a
      difficult intubation scenario and (b) infraglottic airway in a CICV scenario. Chi
      square analysis and Student's t-test were used for categorical and continuous
      variables. Nine-hundred-seventy-one of 2066 surveys were returned. In the
      difficult intubation scenario, the preferred alternative airway devices were
      lighted stylet (45%), fiberoptic bronchoscope (26%), and intubating laryngeal
      mask airway (20%). Only 57% of respondents had encountered a CICV situation in
      real life. In the CICV scenario, preferred infraglottic airways were
      cricothyroidotomy by IV catheter (51%), percutaneous cricothyroidotomy (28%), and
      tracheostomy by surgeon (14%). Anesthesiologists had little experience and were
      uncomfortable with open surgical infraglottic airways. Anesthesiologists with
      experience using infraglottic airways on mannequins were more comfortable using
      them in patients (P < 0.001). In conclusion, in a difficult intubation scenario,
      the lighted stylet has emerged as the preferred alternative airway device. In a
      CICV scenario, respondents preferred cricothyroidotomy by IV catheter, followed
      by percutaneous cricothyroidotomy and tracheostomy by surgeon. Practice on
      mannequins was associated with improved comfort in using infraglottic airways in
      patients.

PMID- 15845703
TI  - The relationship between a pentagastrin-stimulated gastric luminal acid
      production test (Gastrotest) and enteral feeding-related gastrointestinal
      complications in critically ill patients.
AB  - Gastrointestinal feeding-related complications (GICs) are common in critically
      ill patients. Unfortunately, patients at risk for GICs cannot be easily
      identified. Therefore, we performed a prospective study of 20 critically ill
      patients to determine the association between a pentagastrin-stimulated gastric
      acid production test and GICs. Before feeding, the change in the pH of gastric
      juice was measured in response to a subcutaneous injection of pentagastrin
      (Gastrotest). We recorded GICs and the feeding volume ratio during each patient's
      intensive care unit (ICU) stay. Nineteen patients' data were analyzed and 9
      patients (47%) developed > or =1 GIC, including large gastric residuals, 26%;
      abdominal distension, 26%; and vomiting, 21%. Patients with GICs had a longer
      length of ICU stay (mean 21.3, range 5-45 versus 10.1, range 3-32; P < 0.05). The
      9 patients (47%) who were Gastrotest responders before starting enteral feeding
      exhibited a significantly larger volume ratio (P = 0.01) and fewer GICs (1 [11%]
      versus 8 [80%]; P < 0.05). Abdominal distension was seen in only nonresponders.
      The positive and negative predictive values for this test's ability to predict
      GICs were 80% and 88.9%, respectively. Responding to a pentagastrin-stimulated
      gastric luminal acid production test is associated with the administration of
      larger volumes of enteral feed and fewer GICs.

PMID- 15845704
TI  - N-acetyl-cysteine attenuates endotoxin-induced adhesion molecule expression in
      human whole blood.
AB  - Leukocyte adhesion to endothelial cells plays a pivotal role in the early stage
      of endotoxin shock. The attenuation of the leukocyte response to endotoxin may
      contribute to the prevention of further organ dysfunction. Recent evidence
      implies that N-acetyl-cysteine (NAC) attenuates endotoxin-induced
      pathophysiological changes. We investigated the effect of NAC on the expression
      of CD11b and CD62L in endotoxin-stimulated human whole blood. NAC (>10 mM)
      significantly inhibited the lipopolysaccharide (LPS)-induced upregulation of
      CD11b in a concentration-dependent manner. However, NAC did not affect the LPS
      induced downregulation of CD62L. We also analyzed the effect of NAC on
      interleukin-8 (IL-8)-induced expression of CD11b in human whole blood. IL-8 (10
      ng/mL) significantly upregulated the expression of CD11b, and the IL-8-induced
      upregulation was significantly attenuated by NAC (>10 mM) in a dose-dependent
      manner. We conclude that NAC attenuates the increased expression of CD11b in
      either LPS or IL-8-stimulated human whole blood.

PMID- 15845705
TI  - Selective brain hypothermia suppresses noxious-evoked movement in canines.
AB  - Systemic hypothermia suppresses noxious-evoked movement, but its main site of
      action is unknown. We examined the effect of hypothermia in the brain on noxious
      evoked movement by selectively cooling the brain. Sixteen beagles were randomly
      divided into two groups and anesthetized with isoflurane/oxygen. After being
      deeply anesthetized, the dogs' lungs were artificially ventilated, and several
      major vessels were cannulated for perfusion and monitoring. Cold lactate Ringer's
      solution was infused into the right vertebral artery to cool the brain while
      maintaining the trunk temperature relatively warmer. When the brain temperature
      decreased to 20 degrees C or 25 degrees C, isoflurane administration was
      discontinued; the trunk temperatures at this stage were approximately 34.7
      degrees C and 34.6 degrees C, respectively. After the end-tidal isoflurane
      concentration reached 0%, the base of the tail was stimulated with an electric
      current through 2 25-gauge needles. None of the dogs reacted to tail stimulation
      when the brain temperature was at 20 degrees C, whereas 7 of 8 reacted at 25
      degrees C. These results indicate that selective brain hypothermia (20 degrees C)
      results in suppressing noxious-evoked movement in canines.

PMID- 15845706
TI  - The effect of hypocapnia on the autoregulation of cerebral blood flow during
      administration of isoflurane.
AB  - Isoflurane impairs autoregulation of cerebral blood flow in a dose-related
      manner. Previous investigations in several other conditions have demonstrated
      that impaired autoregulation can be restored by hyperventilation. We hypothesized
      that hypocapnia may restore cerebral autoregulation impaired by isoflurane
      anesthesia. We administered isoflurane in 100% oxygen to 12 healthy patients aged
      21-59 yr scheduled for elective nonneurological surgery. Isoflurane end-tidal
      concentration was individualized at 0.1% to 0.2% less than that required to
      induce short periods of isoelectric electroencephalogram. This resulted in an end
      tidal isoflurane concentration of 1.6% +/- 0.2% (mean +/- sd) corresponding to an
      age-adjusted minimum alveolar anesthetic concentration multiple of 1.4. Mean
      arterial blood pressure was reduced to <80 mm Hg, by infusion of remifentanil if
      required. Cerebral autoregulation was assessed by infusing phenylephrine to
      increase mean arterial blood pressure to 100 mm Hg while monitoring middle
      cerebral artery blood flow velocity with transcranial Doppler ultrasonography.
      The change in flow velocity was used to calculate the autoregulation index (ARI).
      The ARI ranges between 0 and 1 and an ARI < or =0.4 indicates significantly
      impaired autoregulation. Autoregulation was tested twice in randomized order:
      once during normocapnia (Paco(2) 38-43 mm Hg) and once during hypocapnia (Paco(2)
      27-34 mm Hg). The median (interquartile range) ARI was 0.29 (0.23-0.64) during
      normocapnia and 0.77 (0.70-0.78) during hypocapnia (P < 0.005). Of the 12
      subjects, autoregulation was significantly impaired in 8 subjects during
      normocapnia and none during hypocapnia (P = 0.001). Hypocapnia restored cerebral
      autoregulation in normal subjects during isoflurane-induced impairment of
      autoregulation.

PMID- 15845707
TI  - Severe seizures during propofol induction in a patient with syringomyelia
      receiving baclofen.
AB  - We report the occurrence of recurrent severe generalized seizures during
      induction of anesthesia with propofol in a patient with syringomyelia receiving
      baclofen for flexor spasms undergoing neurosurgery. We discuss the possible
      epileptogenic interaction between baclofen and propofol in our patient.

PMID- 15845708
TI  - Delayed emergence from anesthesia resulting from cerebellar hemorrhage during
      cervical spine surgery.
AB  - Cerebellar hemorrhage is an unpredictable complication of spinal surgery. We
      encountered a case of cerebellar hemorrhage presenting with delayed emergence
      from anesthesia and hemiplegia after resection of an intradural extramedullar
      tumor from the cervical spine. Postoperative brain computed tomography revealed
      hematoma in the cerebellar vermis and right cerebellar hemisphere. The patient
      made a gradual recovery with conservative treatment. Although the mechanism of
      cerebellar hemorrhage remains speculative, loss of cerebrospinal fluid may play
      an important role. Cerebellar hemorrhage must therefore be considered in patients
      with unexplained neurological deterioration or disturbance on emergence from
      anesthesia after spinal surgery.

PMID- 15845709
TI  - Oral herpes simplex reactivation after intrathecal morphine: a prospective
      randomized trial in an obstetric population.
AB  - There is now evidence for an association between the use of epidural morphine and
      reactivation of herpes simplex labialis (HSL). There are no studies that
      definitively demonstrate the relationship between HSL reactivation and spinal
      intrathecal morphine. To investigate this relationship, we randomized and
      prospectively studied 100 obstetric patients with a history of HSL undergoing
      cesarean delivery under spinal anesthesia. One group received intrathecal
      morphine plus IV morphine via patient-controlled analgesia (ITM+PCA group) for
      postoperative analgesia, and a second group received only IV morphine via patient
      controlled analgesia for postoperative analgesia (PCA-only group). Patients were
      followed for a 30-day period. In the ITM+PCA group 19 (38%) patients had HSL
      reactivation whereas eight (16.6%) had HSL reactivation in the morphine PCA-only
      group (P = 0.028). The incidence of pruritus in the ITM+PCA group was also more
      frequent in the early postoperative period. Our data show HSL reactivation in
      both the ITM+PCA group and PCA-only morphine group, with a more frequent
      incidence in the ITM+PCA group.

PMID- 15845710
TI  - Is transcutaneous electrical stimulation a realistic surrogate for genuine
      surgical stimulation during spinal anesthesia for cesarean delivery?
AB  - Several studies have investigated differential block during spinal anesthesia
      using transcutaneous electrical stimulation (TES) applied to patient's skin.
      These TES stimuli are claimed to be a surrogate for surgical stimulation, but TES
      has never been shown to be a realistic surrogate for a surgical stimulus during
      regional anesthesia. We investigated whether patients could appreciate nonpainful
      TES at the same time as they were undergoing painless cesarean delivery surgery.
      We applied a nonpainful TES (10 mA, 50 Hz, 1-s duration) to the skin, at 5
      different dermatomal levels, in 20 women undergoing elective cesarean delivery
      during spinal anesthesia. During surgery, all the women were totally pain free
      but we noted that the level of block to TES was variable: in 30% of women, TES
      could be felt at the T10 dermatome or more caudally. The first appreciation of
      touch was consistently at T6 or above. The fact that a nonpainful TES stimulus
      could be appreciated within the dermatomes directly involved in transmitting
      surgical stimuli, at a time when the patients were totally pain free, suggests
      that TES at the tested levels is of little value as a surrogate surgical
      stimulus.

PMID- 15845711
TI  - Neuraxial anesthesia and low-molecular-weight heparin prophylaxis in major
      orthopedic surgery in the wake of the latest American Society of Regional
      Anesthesia guidelines.
AB  - In May 2003, the Second American Society of Regional Anesthesia Consensus
      Conference statement was issued partly in response to continued safety concerns
      over the use of regional anesthesia--in particular, neuraxial techniques--with
      low-molecular-weight heparin (LMWH) prophylaxis in major orthopedic surgery. As
      the 2003 Consensus statement makes clear, regional anesthesia may be used safely
      with LMWH prophylaxis. The key to optimizing patient safety, however, depends on
      a careful calibration of the total daily dose and the timing of the first and
      subsequent doses of the LMWH drug with the timing and management of the regional
      anesthetic procedure. Because the challenge of successfully providing regional
      anesthesia in the presence of LMWH thromboprophylaxis is a clinical one,
      anesthesiologists should do what they can to ensure that every member of the
      surgical team has an understanding of current literature and practice guidelines
      such as those recently published by the American Society of Regional Anesthesia.

PMID- 15845712
TI  - Neurologic sequelae after interscalene brachial plexus block for shoulder/upper
      arm surgery: the association of patient, anesthetic, and surgical factors to the
      incidence and clinical course.
AB  - We determined the incidence, distribution, and resolution of neurologic sequelae
      and the association with anesthetic, surgical, and patient factors after single
      injection interscalene block (ISB) using levobupivacaine 0.625% with epinephrine
      1:200,000 in subjects undergoing shoulder or upper arm surgery, or both, in 693
      consecutive adult patients. After a standardized ISB, assessments were made at 24
      and 48 h and at 2 and 4 wk for anesthesia, hypesthesia, paresthesias,
      pain/dysesthesias, and motor weakness. Symptomatic patients were monitored until
      resolution. Subjects reporting pain or discomfort >3 of 10 and those with motor
      or extending sensory symptoms received diagnostic assessment. Six-hundred-sixty
      subjects completed 4 wk of follow-up. Fifty-eight neurologic sequelae were
      reported by 56 subjects. Symptoms were sensory except for two cases of motor
      weakness (lesions identified distant from the ISB site). Thirty-one sequelae with
      likely ISB association were reported by 29 subjects, including 14 at the ISB
      site, 9 at the distal phalanx of thumb/index finger, 7 involving the posterior
      auricular nerve, and 1 clinical brachial plexopathy. Sequelae not likely
      associated with the ISB were reported by 27 subjects with symptoms reported in
      the median (n = 9) and ulnar (n = 4) nerves, surgical neuropraxias (n = 12), and
      motor weakness (n = 2). Symptoms resolved spontaneously (median 4 wk; range, 2-16
      wk) except in the two patients with motor weaknesses and the patient with
      clinical brachial plexopathy, who received therapeutic interventions. Variables
      identified as independent predictors of neurologic sequelae likely related to ISB
      were paresthesia at needle insertion and ISB site pain or bruising at 24 h. In
      contrast, surgery preformed in the sitting position, as well as ISB site
      bruising, was identified as a predictor of neurologic sequelae not likely related
      to ISB. In conclusion, neurologic sequelae after single-injection ISB using
      epinephrine mainly involve transient minor sensory symptoms.

PMID- 15845713
TI  - Patient-controlled interscalene analgesia after shoulder surgery: catheter
      insertion by the posterior approach.
AB  - Insertion and maintenance of an interscalene catheter is technically challenging
      using lateral or anterior approaches. We report a technique to provide continuous
      brachial plexus blockade through a 48-h infusion of ropivacaine 0.1% (5 mL/h with
      a 5 mL bolus dose, 20-min lockout interval) using a catheter inserted with
      cannula-over-needle technique on the posterior side of the neck in 120 patients
      undergoing shoulder surgery. All catheters were successfully placed. There were
      no technical complications (impossibility to thread catheter, accidental
      vascular, epidural or subarachnoid location), catheter dislodgment, or analgesic
      solution leakage. Dysphonia, Horner's syndrome, and difficulty breathing were
      observed in 12 patients, four patients, and one patient, respectively. One
      patient complained of minor paresthesia that spontaneously resolved. Three
      patients complained of cervical pain. Pain scores as well as ropivacaine
      requirement via a patient-controlled analgesia device were low. Evaluation of
      acute and nonacute complications in a large-size study is needed to compare
      efficacy and safety of this approach with existing techniques.

PMID- 15845714
TI  - The median effective dose of intrathecal hyperbaric bupivacaine is larger in the
      single-shot spinal as compared with the combined spinal-epidural technique.
AB  - The combined spinal-epidural technique (CSE) has been associated with prolonged
      motor recovery and more frequent arterial hypotension as compared with a single
      shot spinal (SSS) technique. We determined the median effective dose (MED) of
      intrathecal hyperbaric bupivacaine for CSE and SSS by using the up-down
      sequential allocation technique. Sixty male patients were randomly allocated to
      receive intrathecal administration through an SSS or CSE technique. Needle
      insertion occurred at the L3-4 interspace in all patients. In SSS, 9.5 mg of
      hyperbaric bupivacaine was administered through a 27-gauge Whitacre spinal
      needle. In CSE, a 17-gauge Tuohy needle with 4 mL of air was used to locate the
      epidural space, through which a 27-gauge Whitacre spinal needle was introduced
      and 7.0 mg of hyperbaric bupivacaine was administered. The dosing adjustment was
      0.5 mg. A "successful" outcome was arbitrarily defined as sensory anesthesia at
      or above the T6 dermatome lasting for 60 min. A "success" resulted in a 0.5-mg
      decrement, whereas a "failure" resulted in a 0.5-mg increment in the next
      patient. There were 13 successes in both groups. The MED of bupivacaine was 9.18
      mg (95% confidence interval, 8.89-9.47 mg) for CSE as compared with 11.37 mg (95%
      confidence interval, 10.88-11.86 mg) for SSS (P < 0.001). CSE required 19.3% (95%
      confidence interval, 14.9%-23.6%) less local anesthetic to achieve the defined
      clinical target. We found significant discrepancies in the MED of hyperbaric
      bupivacaine between the two techniques. Under similar clinical conditions, a 20%
      decrement in the dose of bupivacaine may be warranted whenever CSE is intended in
      place of SSS.

PMID- 15845715
TI  - Does femoral nerve catheter placement with stimulating catheters improve
      effective placement? A randomized, controlled, and observer-blinded trial.
AB  - Continuous peripheral nerve blocks offer the benefit of extended postoperative
      analgesia and accelerated functional recovery after major knee surgery.
      Conventional nerve localization is performed over a stimulating needle followed
      by blind insertion of the peripheral catheter. Correct catheter placement is
      confirmed by testing for satisfactory analgesia. Stimulating catheters offer the
      advantage of verifying correct placement close to the nerve during catheter
      placement. The aim of this randomized trial was to determine whether accurate
      catheter positioning under continuous stimulation accelerates the onset of
      sensory and motor block, improves the quality of postoperative analgesia, and
      enhances functional recovery. We compared femoral nerve catheters inserted under
      continuous stimulation with catheters that were placed using the conventional
      technique of blind advancement in 81 patients undergoing major knee surgery. Time
      of catheter placement was similar in both groups with 4 min (3/7.3; median,
      25th/75th percentile) in the conventional group and 5 min (4/8.8) in the
      stimulating catheter group. In both groups, 42% of the catheters could be
      correctly placed (motor response of the patella with a current < or =0.5 mA) at
      first attempt. In 22 patients (58%) of the stimulating catheter group, the
      catheter had to be redirected 1-20 times, including 2 that could not be correctly
      placed within 20 min. The onset time of sensory and motor block was almost
      similar in both groups. There were no differences in the postoperative IV opioid
      consumption, and visual analog scale pain scores at rest and movement, or maximal
      bending and stretching of the knee joint during the 5 days after surgery. We
      conclude that with continuous femoral nerve blocks, blind catheter advancement is
      as effective as the stimulating catheter technique with respect to onset time of
      sensory and motor block as well as for postoperative pain reduction and
      functional outcome.

PMID- 15845716
TI  - Does the sciatic nerve approach influence thigh tourniquet tolerance during below
      knee surgery?
AB  - In this prospective, randomized, blinded study we assessed thigh tourniquet
      tolerance when a Labat's or a posterior popliteal approach of the sciatic nerve
      was used for below-knee surgery. One-hundred-twenty patients were divided into
      two groups of 60. A posterior popliteal (Group 1) or a Labat's (Group 2) sciatic
      nerve block was performed with 25 mL 1% mepivacaine + epinephrine 1:200,000. In
      both groups, a femoral nerve block was achieved. Patient comfort during block
      performance, sensory block, success rate, and thigh tourniquet tolerance were
      recorded. Performance of the block was significantly more comfortable in Group 1
      than in Group 2 (P < 0.01). Completeness of the block at t(30 min.) and success
      rate were comparable in both groups. Thigh tourniquet pain increased with time in
      both groups. No statistically significant difference was observed between groups.
      We conclude that despite a complete sensory blockade of the posterior femoral
      cutaneous nerve in 91% of the patients, Labat's approach of the sciatic nerve
      provides no better thigh tourniquet tolerance than the popliteal approach. The
      popliteal approach is as efficient but more comfortable for the patient and is
      the preferred technique for below-knee surgery.

PMID- 15845717
TI  - Neurologic complication after anterior sciatic nerve block.
AB  - The lack of reported complications related to lower extremity peripheral nerve
      blocks (PNBs) may be related to the relatively infrequent application of these
      techniques and to the fact that most such events go unpublished. Our current
      understanding of the factors that lead to neurologic complications after PNBs is
      limited. This is partly the result of our inability to conduct meaningful
      retrospective studies because of a lack of standard and objective monitoring and
      documentation procedures for PNBs. We report a case of permanent injury to the
      sciatic nerve after sciatic nerve block through the anterior approach and discuss
      mechanisms that may have led to the injury. Intraneural injection and nerve
      injury can occur in the absence of pain on injection and it may be heralded by
      high injection pressure (resistance).

PMID- 15845718
TI  - A randomized, double-blind comparison of lactated Ringer's solution and 0.9% NaCl
      during renal transplantation.
AB  - Normal saline (NS; 0.9% NaCl) is administered during kidney transplantation to
      avoid the risk of hyperkalemia associated with potassium-containing fluids.
      Recent evidence suggests that NS may be associated with adverse effects that are
      not seen with balanced-salt fluids, e.g., lactated Ringer's solution (LR). We
      hypothesized that NS is detrimental to renal function in kidney transplant
      recipients. Adults undergoing kidney transplantation were enrolled in a
      prospective, randomized, double-blind clinical trial of NS versus LR for
      intraoperative IV fluid therapy. The primary outcome measure was creatinine
      concentration on postoperative Day 3. The study was terminated for safety reasons
      after interim analysis of data from 51 patients. Forty-eight patients underwent
      living donor kidney transplants, and three patients underwent cadaveric donor
      transplants. Twenty-six patients received NS, and 25 patients received LR. There
      was no difference between groups in the primary outcome measure. Five (19%)
      patients in the NS group versus zero (0%) patients in the LR group had potassium
      concentrations >6 mEq/L and were treated for hyperkalemia (P = 0.05). Eight (31%)
      patients in the NS group versus zero (0%) patients in the LR group were treated
      for metabolic acidosis (P = 0.004). NS did not adversely affect renal function.
      LR was associated with less hyperkalemia and acidosis compared with NS. LR may be
      a safe choice for IV fluid therapy in patients undergoing kidney transplantation.

PMID- 15845719
TI  - Does measurement of preoperative anxiety have added value for predicting
      postoperative nausea and vomiting?
AB  - Preoperative anxiety has been suggested as a predictor of postoperative nausea
      and vomiting (PONV), but supporting data are lacking. We quantified the added
      predictive value of preoperative anxiety to established predictors of PONV in
      1389 surgical inpatients undergoing various procedures, by using multivariate
      logistic regression analysis. Investigated predictors were a history of PONV or
      motion sickness, smoking, sex, age, ethnicity, body mass index, ASA physical
      status, surgery type, duration of anesthesia, anesthetic technique, and
      postoperative opioid analgesia. Anxiety was measured by the Spielberger State
      Trait Anxiety Inventory and the Amsterdam Preoperative Anxiety and Information
      Scale. The outcome was the occurrence of PONV in the first 24 h after surgery.
      The area under the receiver operating characteristic curve of a multivariate
      (logistic regression) model including sex, age, smoking, history of PONV or
      motion sickness, surgery type, and anesthetic technique was 0.72 (95% confidence
      interval, 0.70-0.74). There was a weak but significant association of anxiety
      with PONV, but the addition of anxiety to the model did not further increase the
      area under the receiver operating characteristic curve. Therefore, routine
      preoperative measurement of anxiety does not seem warranted, provided that the
      other predictors are already considered.

PMID- 15845720
TI  - Estimation of the length of the nares-vocal cord.
AB  - The nasal route is preferred for fiberoptic intubation. Placing a lubricated
      endotracheal tube through the nostril can guide the fiberoptic scope towards the
      larynx. It would be helpful for optimal visualization of the vocal cord when the
      scope is passed through the endotracheal tube if the length of nares-vocal cord
      (NV length) could be predicted and the tip of the endotracheal tube could be
      placed close to the vocal cord. In this study we measured the NV length and
      examined the relationship between the NV length and various external
      measurements. Using a fiberoptic scope, the NV lengths were measured in 50 male
      and 45 female patients scheduled to undergo elective surgery under general
      anesthesia. In addition, the distances from the lateral border of the nares to
      tragus of the ear (NE distance) and to the angle of the mandible (NM distance)
      were measured. The age, height, and weight of all the patients were recorded. The
      NV length of the males was 18.3 +/- 0.8 cm, and that of the females was 16.3 +/-
      0.7 cm. The relationship between the NV length and body height (P < 0.001, r =
      0.755) and the NE distance (P < 0.001, r = 0.636) showed a significant
      correlation but NM distance did not (P = 0.075). The length of the NV cord can be
      predicted using the body height or the NE distance.

PMID- 15845724
TI  - AIS' current role in anesthesiology risk management remains uncertain.

PMID- 15845726
TI  - Effects of hydroxyethyl starch and calcium on platelet activation.

PMID- 15845728
TI  - Skin sensitivity to rocuronium and vecuronium: prick-tests are not intradermal
      test.

PMID- 15845729
TI  - An uncommon complication of thoracic epidural anesthesia: pleural puncture.

PMID- 15845730
TI  - Local anesthetics for breakthrough pain in patients receiving intrathecal
      treatment for cancer pain management.

PMID- 15845731
TI  - Measurement of isoflurane and desflurane degradation.

PMID- 15845732
TI  - Cervical plexus block provides postoperative analgesia after clavicle surgery.

PMID- 15845734
TI  - Dangerous design flaw in the Ohmeda Aespire anesthesia system.

PMID- 15845735
TI  - How likely is awareness during anesthesia?

PMID- 15845736
TI  - Concern about the safety of Introcan Safety intravenous catheters.

PMID- 15845738
TI  - Accidental epidural injection of pancuronium.

PMID- 15845739
TI  - Can capnography substitute for auscultation in sedation cases?

PMID- 15845741
TI  - Peripheral nerve blocks for postoperative pain relief after total knee
      replacement: more questions than answers.

PMID- 15845742
TI  - Dexamethasone dose attenuates pain on injection following diazepam hydrochloride.

PMID- 15845744
TI  - Does paralysis contribute to awareness under anesthesia?

PMID- 15845745
TI  - Airway obstruction due to a damage to the laryngeal mask.

PMID- 15845746
TI  - Progesterone inhibits the estrogen-induced phosphoinositide 3-kinase-->AKT-->GSK
      3beta-->cyclin D1-->pRB pathway to block uterine epithelial cell proliferation.
AB  - The mammalian cell cycle is regulated by the cyclin/cyclin-dependent kinase (CDK)
      phosphorylation of the retinoblastoma (pRB) family of proteins. Cyclin D1 with
      its CDK4/6 partners initiates the cell cycle and acts as the link between
      extracellular signals and the cell cycle machinery. Estradiol-17beta (E2)
      stimulates uterine epithelial cell proliferation, a process that is completely
      inhibited by pretreatment with progesterone (P4). Previously, we identified
      cyclin D1 localization as a key point of regulation in these cells with E2
      causing its nuclear accumulation and P4 retaining it in the cytoplasm with the
      resultant inhibition of pRB phosphorylation. Here we show that E2 stimulates
      phosphoinositide 3-kinase to activate phosphokinase B/AKT to effect an inhibitory
      phosphorylation of glycogen synthase kinase (GSK-3beta). This pathway is
      suppressed by P4. Inhibition of the GSK-3beta activity in P4-treated uteri by the
      specific inhibitor, LiCl, reversed the nuclear accumulation of cyclin D1 and in
      doing so, caused pRB phosphorylation and the induction of downstream genes,
      proliferating cell nuclear antigen and Ki67. Conversely, inhibition of
      phosphoinositide 3 kinase by LY294002 or Wortmanin reversed the E2-induced GSK
      3beta Ser9 inhibitory phosphorylation and blocked nuclear accumulation of cyclin
      D1. These data show the reciprocal actions of E2 and P4 on the phosphoinositide 3
      kinase through to the GSK-3beta pathway that in turn regulates cyclin D1
      localization and cell cycle progression. These data reveal a novel signaling
      pathway that links E2 and P4 action to growth factor-mediated signaling in the
      uterus.

PMID- 15845747
TI  - Pathophysiological and clinical aspects of combat anticholinesterase poisoning.
AB  - Nerve agents are organophosphate compounds similar to those used as pesticides
      but with much higher toxicity. They all block the activity of the enzyme
      acetylcholine esterase. Victims are intoxicated by absorption of the toxin via
      exposed skin or, more commonly, via inhalation of the poisonous gas. The
      resultant clinical picture is of hyperstimulation of both the nicotinic and
      muscarinic cholinergic system, which, if not promptly treated, leads to severe
      muscle paralysis, cardiac brady-asystole, hypersecretion from secretory glands,
      respiratory failure, seizures, coma and death. If antidotal drugs are promptly
      administered, the clinical severity of the poisoning is attenuated or complete
      abortion of symptoms is obtained. The main therapeutic strategies include
      atropine and oximes that counteract the nerve-agent-induced muscarinic and
      nicotinic cholinergic symptoms, respectively. Anticonvulsants and sedatives are
      used to treat central nervous system acetylcholine esterase disarray. This review
      summarizes the biochemistry and pathophysiology of anticholinesterase poisoning,
      the relevant clinical manifestations and the currently available therapeutic
      strategies.

PMID- 15845748
TI  - Advances in epilepsy.
AB  - Advances in understanding of both the causes and consequences of epilepsy have
      been paralleled by a number of recent reports and clinical guidelines
      highlighting the complexities involved in both diagnosing and treating epilepsy.
      We review recent developments, including comments on the evolution of clinical
      guidelines, anti-epileptic drugs, epilepsy surgery and new treatment approaches
      in development. Epilepsy genetics and emerging evidence on mechanisms of drug
      resistance in epilepsy will also be discussed. Issues with respect to pregnancy
      and epilepsy are considered, together with more recently identified dilemmas
      including bone health in epilepsy and whether seizures themselves cause brain
      damage. Imaging in epilepsy has recently been reviewed elsewhere, and will not be
      discussed.

PMID- 15845749
TI  - Midazolam and cyclosporin a metabolism in transgenic mice with liver-specific
      expression of human CYP3A4.
AB  - Cytochrome P450 3A4 (CYP3A4) is a major determinant of the metabolism of many
      drugs, including important anticancer drugs, with sometimes profound impact on
      therapeutic efficacy and toxic side effects. To study in vivo CYP3A(4) functions,
      we have generated and characterized transgenic mice with functional expression of
      human CYP3A4 cDNA in the liver. Two transgenic lines displayed substantial,
      physiologically relevant and stable CYP3A4 levels in liver and moderate levels in
      kidney, but not in small intestine. The mice did not display obvious
      physiological abnormalities. The CYP3A4 substrate drugs midazolam and cyclosporin
      A were used to test functional activity of CYP3A4 in liver. The area under the
      plasma concentration versus time curve (AUC) of intravenously administered
      midazolam (30 mg/kg) was 2.2-fold decreased in the transgenic mice compared with
      wild-type (5.45 +/- 0.21 versus 11.7 +/- 0.46 microg . h ml(-1); P < 0.01), and
      early formation of the primary metabolite 1-hydroxymidazolam was about 2-fold
      increased, demonstrating the functionality of CYP3A4 in the liver. Similarly,
      following intravenous administration of cyclosporin A (20 mg/kg), CYP3A4
      transgenic mice displayed a reduced plasma AUC compared with wild-type (24.3 +/-
      0.66 versus 35.8 +/- 0.53 microg . h ml(-) (1); P < 0.01). Thus, midazolam and
      cyclosporin A, compounds with markedly different clearance rates and half-lives,
      both demonstrated clearly accelerated kinetics in the CYP3A4 transgenic mice. We
      expect that this CYP3A4 transgenic model will provide a useful tool to study the
      impact of CYP3A4 on drug levels, especially when combined with other transgenic
      and knockout strains.

PMID- 15845750
TI  - Synthesis and characterization of some new phase II metabolites of the alkylator
      bendamustine and their identification in human bile, urine, and plasma from
      patients with cholangiocarcinoma.
AB  - The alkylating agent bendamustine is currently in phase III clinical trials for
      the treatment of hematological malignancies and breast, lung, and
      gastrointestinal tumors. Renal elimination mainly as the parent compound is
      thought to be the primary route of excretion. Because polar biliary conjugates
      were expected metabolites of bendamustine, three cysteine S-conjugates were
      synthesized, purified by quantitative high-performance liquid chromatography
      (HPLC), and characterized by NMR spectroscopy and mass spectrometry (MS). HPLC
      assays with MS, as well as fluorescence detection of bile, urine, and plasma
      after single-dose intravenous infusion of 140 mg/m(2) bendamustine in five
      subjects with cholangiocarcinoma, indicated the existence of these phase II
      metabolites, which were identified as cysteine S-conjugates by comparison with
      the previously characterized synthetic reference standards. The sum of the three
      cysteine S-conjugates of bendamustine was determined in human bile and urine to
      be 95.8 and 26.0%, respectively, expressed as mean percentage of the sum of the
      parent compound and identified metabolites. The percentage of administered dose
      recovered in urine as cysteine S-conjugates ranged from 0.9 to 4.1%, whereas the
      total percentage of the administered dose excreted in urine as the parent drug
      and seven metabolites ranged from 3.8 to 16.3%. The identification of cysteine S
      conjugates provide evidence that a major route of bendamustine metabolism in
      humans involves conjugation with glutathione. Results indicate the importance of
      phase II conjugation in the elimination of bendamustine, besides phase I
      metabolism and hydrolytic degradation, and require further investigation.

PMID- 15845751
TI  - Bipolar disorder in older persons: perspectives and new findings.

PMID- 15845752
TI  - Electroconvulsive therapy: a selected review.
AB  - Since its introduction in 1938, electroconvulsive therapy (ECT) has remained an
      important treatment for selected serious neuropsychiatric illnesses and continues
      to be one of the most effective treatments in psychiatry. ECT has evolved into a
      technically sophisticated procedure with a proven track record of safety. For
      this review, the authors relied heavily on the database from the APA Task Force
      Report on ECT (2001), updated with additional searches of computerized literature
      databases for the period 1999-2003. The review is necessarily a selective one,
      given the exponential growth of literature in the field. The authors attempt to
      summarize key areas of ECT practice, informed by relevant research findings and
      expert consensus when applicable. The authors also point out areas of controversy
      and gaps in our present knowledge. Although this review summarizes the scientific
      literature about the use of ECT generally, emphasis is given to describing
      literature pertaining to the treatment of geriatric patients when such
      information is available or when older patients or the disorders from which they
      suffer merit special consideration.

PMID- 15845753
TI  - New-onset bipolar disorder in later life.
AB  - OBJECTIVE: This analysis of a large VA database evaluated differences in clinical
      presentation, health service use, and psychotropic medication utilization among
      16,330 patients with bipolar disorder age 60 and older. Selected differences were
      compared between new-onset and earlier-onset groups. METHODS: Geriatric patients
      with new-onset bipolar illness (NOI) were compared with geriatric patients with
      earlier-onset bipolar illness (EOI) on selected clinical variables and on health
      resource utilization. RESULTS: Among the 65,556 individuals with bipolar disorder
      treated in the VA in federal fiscal year 2001 (FY 01), 16,330 (24.9%) were age 60
      or older. The large majority, 13,477 (82.5%), had earlier-onset bipolar illness,
      whereas 1,000 individuals (6.1%) had apparently new-onset bipolar disorder. A
      fairly consistent pattern in health resource use when comparing new- versus
      earlier-onset bipolar disorder was overall less resource utilization by
      individuals with new-onset illness. As compared with EOI individuals, NOI
      individuals have less outpatient care overall and fewer mental health care
      visits. CONCLUSIONS: Bipolar disorder among older adults is common in the VA and
      is an increasingly emphasized problem in older non-VA populations, as well.
      Health service use by older adults with bipolar disorder is high, and includes
      substantial utilization of inpatient non-psychiatric care. Distinctions between
      earlier- and new-onset bipolar disorder have important implications with respect
      to illness presentation and health resource utilization.

PMID- 15845754
TI  - Differences in clinical features and mental health service use in bipolar
      disorder across the lifespan.
AB  - OBJECTIVE: Because of the scarcity of research in geriatric bipolar disorder, the
      authors examined the prevalence, clinical features, and service use of persons
      with bipolar disorder among older adults treated in a large public mental health
      system. METHODS: From San Diego County's Adult and Older-Adult Mental Health
      Services database (N=34,970, fiscal year 2002-2003), the authors selected
      patients with bipolar disorder, divided them into three age-groups (young: age 18
      39, middle-aged: age 40-59, and elderly: age 60+) and compared them on
      demographic, clinical, and mental health service use characteristics. RESULTS:
      The authors identified 2,903 patients who received services for bipolar disorder
      at least once during the fiscal year, accounting for a slightly lower proportion
      of diagnosis among elderly patients (7.0%) than middle-aged (8.7%) or younger
      groups (8.3%). Elderly patients were less likely to have substance use disorder
      comorbidity, but more likely to have a cognitive disorder diagnosis and lower
      global functioning scores than their younger counterparts. Elderly bipolar
      patients were less likely than younger groups to use inpatient, outpatient, and
      emergency room psychiatric care, but more likely to use case-management and
      conservator services. DISCUSSION: Bipolar disorder was only slightly less common
      among elderly patients in a large, public mental health system, compared to
      younger age-groups. Available clinical data revealed a mixed picture of bipolar
      disorder in late life, with more functional and cognitive impairment and less
      substance use disorder comorbidity and use of acute psychiatric services. Our
      findings suggest that older adults with bipolar disorder have unique mental
      health service needs.

PMID- 15845755
TI  - New thyroxine treatment in older adults beginning lithium therapy: implications
      for clinical practice.
AB  - OBJECTIVE: The authors sought to determine the incidence of lithium-induced
      hypothyroidism in a population-based cohort of older adults beginning lithium
      therapy and thereby to inform clinical guidelines on the frequency of monitoring
      necessary in this group. METHODS: The authors conducted a population-based
      observational cohort study using four administrative databases that contained
      information on over 1.3 million older adults in Ontario who receive universal
      healthcare coverage in terms of physician services, drugs, and hospitalizations.
      Over an 18-month period, they studied adults age>or=65 who were newly prescribed
      lithium or valproate, monitoring subjects for initiation of T4 therapy (as a
      proxy for hypothyroidism) while they continued their lithium use. RESULTS: The
      authors identified 1,705 new users of lithium and 2,406 new users of valproate
      with similar baseline characteristics. Lithium users were significantly more
      likely to be treated with T4 than were valproate users. The rate of T4 treatment
      per 100 person-years was 5.65 in the lithium group and 2.70 in the valproate
      group. CONCLUSION: T4 treatment was initiated in almost 6% of lithium-treated
      patients, suggesting the possibility that hypothyroidism developed twice as
      frequently among these patients as would be expected among a mixed-age
      population. Increased vigilance and continued monitoring of thyroid functioning
      for at least 2 years is necessary in older adults beginning lithium therapy.

PMID- 15845756
TI  - Maintenance treatment outcomes in older patients with bipolar I disorder.
AB  - OBJECTIVE: The efficacy and tolerability of mood stabilizers in older adults with
      bipolar disorder remains understudied. Authors retrospectively examined response
      to lamotrigine, lithium, and placebo in older (>or=age 55) adults with Bipolar I
      disorder (DSM-IV) who participated in two mixed-age, maintenance studies
      examining time to intervention for an emerging mood episode
      (manic/hypomanic/mixed or depressed) and drug tolerability. METHODS: In all, 588
      patients received double-blind lamotrigine (LTG, 100 mg-400 mg/day), lithium (Li,
      0.8 mEq/L-1.1 mEq/L), or placebo (PBO); data from 98 older adults (LTG: 33, Li:
      34, PBO: 31) were examined. Mean modal total daily doses were LTG 240 mg and Li
      750 mg. RESULTS: LTG significantly delayed time to intervention for any mood
      episode and for a depressive episode, compared with placebo. Li significantly
      delayed time to intervention for mania/hypomania/mixed compared with placebo.
      Back pain and headache were the most common adverse events during LTG treatment;
      rash: LTG, 3%; Li, 6%; and PBO, 0; no serious rash was reported. The most common
      adverse events (>10%) during lithium treatment were dyspraxia, tremor,
      xerostomia, headache, infection, amnesia, dizziness, diarrhea, nausea, and
      fatigue. CONCLUSION: Lamotrigine and lithium may be effective and well-tolerated
      maintenance therapies for older adults with Bipolar I depression.

PMID- 15845757
TI  - Effects of previous major depressive illness on cognition in Alzheimer disease
      patients.
AB  - OBJECTIVE: Major Depressive Disorder (MDD) may be a risk factor for subsequent
      development of irreversible dementia; however, the influence of a premorbid
      history of MDD on the clinical course of patients diagnosed with probable
      Alzheimer disease (AD) has not been fully explored. METHODS: Forty-three AD
      patients with mild-to-moderate cognitive impairment were screened for a life-long
      history of MDD with the Clinical Assessment of Depression in Dementia Scale.
      Twenty-two subjects had a history of MDD before onset of cognitive impairment,
      but none was suffering from an MDD episode at time of cognitive assessment.
      RESULTS: After controlling for age, education, duration of illness, gender, and
      medication status, subjects with a history of MDD had significantly lower scores,
      as a group, on cognitive performance tests, including the Mini-Mental State Exam,
      WAIS Full-Scale and Verbal Scale I.Q., and the Initiation/Perseveration subscale
      of the Mattis Dementia Rating Scale. These subjects also developed symptoms of
      dementia at a significantly earlier age than the subjects who had no premorbid
      history of MDD. CONCLUSIONS: Although previous studies have shown that late-onset
      MDD may increase risk for subsequent dementia, the current results suggest that
      premorbid MDD is associated with more severe cognitive deficits during the actual
      course of dementia.

PMID- 15845758
TI  - A pilot study of standardized treatment in geriatric bipolar disorder.
AB  - OBJECTIVE: The authors sought to determine the feasibility of treating elderly
      adults with bipolar disorder under standardized-treatment conditions. METHODS:
      Thirty-one patients age 60 and older with bipolar disorder were treated in
      standardized pathways. Mood state was checked at each study visit with the
      Hamilton Rating Scale for Depression-17 item (Ham-D-17) and the Young Mania
      Rating Scale (YMRS). RESULTS: Defining "well days" as both Ham-D and YMRS scores
      of <or=10, the mean percentage of well days was 72.5 (range: 0%-100%) over study
      participation. CONCLUSIONS: Treating older adults with bipolar disorder under
      standardized treatment is feasible and is associated with low symptom levels.
      However, most older adults with bipolar disorder do not experience sustained
      recovery.

PMID- 15845759
TI  - Cognitive, behavioral, and physiological changes in Alzheimer disease patients as
      a function of incontinence medications.
AB  - OBJECTIVE: Authors evaluated the cognitive, neurophysiologic, and behavioral
      effects of incontinence medications in patients with Alzheimer disease (AD).
      METHODS: Nine patients were evaluated, both on and off incontinence medication,
      for cognitive status, neuropsychiatric status, activities of daily living, and
      serum anticholinergic level. Caregivers were interviewed to evaluate behavioral
      status and caregiver burden. RESULTS: Patients showed better performance on
      specific measures of cognition and behavior when not taking medication for
      incontinence. A significant, inverse correlation was found between mental status
      and anticholinergic level. CONCLUSION: Although the sample size was small, the
      findings suggest that, in patients with AD, incontinence medications with
      anticholinergic properties may have detrimental effects on mental status and
      behavior.

PMID- 15845760
TI  - Race and vascular depression risk in community-dwelling older adults.
AB  - OBJECTIVE: Authors examined racial differences in cerebrovascular risk factors
      (CVRFs) and overall depressive symptomatology. METHODS: The authors applied a
      correlational design using a depression inventory, the Center for Epidemiological
      Studies Depression scale (CES-D) and self-report CVRF data from black and white
      community-dwelling elderly subjects (N=362). RESULTS: Black subjects were more
      likely than whites to screen positive for depression, but there were no race
      differences in CVRFs. Across races, greater rates of CVRFs were associated with
      higher scores on the CES-D. CVRFs and lower education level were independent
      predictors of positive depression screening on the CES-D. CONCLUSIONS: CVRFs were
      associated with depression in black and white elderly subjects. Future research
      should examine race differences within vascular depression, utilizing broader
      measures of CVRFs.

PMID- 15845761
TI  - Corticobasal degeneration substantiated by imaging studies.

PMID- 15845763
TI  - Genes required for rapid expression of nitrogenase activity in Azotobacter
      vinelandii.
AB  - Rnf proteins are proposed to form membrane-protein complexes involved in the
      reduction of target proteins such as the transcriptional regulator SoxR or the
      dinitrogenase reductase component of nitrogenase. In this work, we investigate
      the role of rnf genes in the nitrogen-fixing bacterium Azotobacter vinelandii. We
      show that A. vinelandii has two clusters of rnf-like genes: rnf1, whose
      expression is nif-regulated, and rnf2, which is expressed independently of the
      nitrogen source in the medium. Deletion of each of these gene clusters produces a
      time delay in nitrogen-fixing capacity and, consequently, in diazotrophic growth.
      Deltarnf mutations cause two distinguishable effects on the nitrogenase system:
      (i), slower nifHDK gene expression and (ii), impairment of nitrogenase function.
      In these mutants, dinitrogenase reductase activity is lowered, whereas
      dinitrogenase activity remains essentially unaltered. Further analysis indicates
      that deltarnf mutants accumulate an inactive and iron-deficient form of NifH
      because they have lower rates of incorporation of [4Fe-4S] into NifH. Deltarnf
      mutations also cause a noticeable decrease in aconitase activity; however, they
      do not produce general oxidative stress or modification of Fe metabolism in A.
      vinelandii. Our results suggest the existence of a redox regulatory mechanism in
      A. vinelandii that controls the rate of expression and maturation of nitrogenase
      by the activity of the Rnf protein complexes. rnf1 plays a major and more
      specific role in this scheme, but the additive effects of mutations in rnf1 and
      rnf2 indicate the existence of functional complementation between the two
      homologous systems.

PMID- 15845764
TI  - The Pseudomonas syringae effector AvrRpt2 cleaves its C-terminally acylated
      target, RIN4, from Arabidopsis membranes to block RPM1 activation.
AB  - Plant pathogenic Pseudomonas syringae deliver type III effector proteins into the
      host cell, where they function to manipulate host defense and metabolism to
      benefit the extracellular bacterial colony. The activity of these virulence
      factors can be monitored by plant disease resistance proteins deployed to "guard"
      the targeted host proteins. The Arabidopsis RIN4 protein is targeted by three
      different type III effectors. Specific manipulation of RIN4 by each of them leads
      to activation of either the RPM1 or RPS2 disease resistance proteins. The type
      III effector AvrRpt2 is a cysteine protease that is autoprocessed inside the host
      cell where it activates RPS2 by causing RIN4 disappearance. RIN4 contains two
      sites related to the AvrRpt2 cleavage site (RCS1 and RCS2). We demonstrate that
      AvrRpt2-dependent cleavage of RIN4 at RCS2 is functionally critical in vivo. This
      event leads to proteasome-mediated elimination of all but a membrane-embedded
      approximately 6.4-kDa C-terminal fragment of RIN4. One or more of three
      consecutive cysteines in this C-terminal fragment are required for RIN4
      localization; these are likely to be palmitoylation and/or prenylation sites.
      AvrRpt2-dependent cleavage at RCS2, and release of the remainder of RIN4 from the
      membrane, consequently prevents RPM1 activation by AvrRpm1 or AvrB. RCS2 is
      contained within the smallest tested fragment of RIN4 that binds AvrB in vitro.
      Thus, at least two bacterial virulence factors target the same domain of RIN4, a
      approximately 30-aa plant-specific signature sequence found in a small
      Arabidopsis protein family that may be additional targets for these bacterial
      virulence factors.

PMID- 15845765
TI  - A specific subdomain in phi29 DNA polymerase confers both processivity and strand
      displacement capacity.
AB  - Recent crystallographic studies of phi29 DNA polymerase have provided structural
      insights into its strand displacement and processivity. A specific insertion
      named terminal protein region 2 (TPR2), present only in protein-primed DNA
      polymerases, together with the exonuclease, thumb, and palm subdomains, forms two
      tori capable of interacting with DNA. To analyze the functional role of this
      insertion, we constructed a phi29 DNA polymerase deletion mutant lacking TPR2
      amino acid residues Asp-398 to Glu-420. Biochemical analysis of the mutant DNA
      polymerase indicates that its DNA-binding capacity is diminished, drastically
      decreasing its processivity. In addition, removal of the TPR2 insertion abolishes
      the intrinsic capacity of phi29 DNA polymerase to perform strand displacement
      coupled to DNA synthesis. Therefore, the biochemical results described here
      directly demonstrate that TPR2 plays a critical role in strand displacement and
      processivity.

PMID- 15845767
TI  - Auxiliary basis expansions for large-scale electronic structure calculations.
AB  - One way to reduce the computational cost of electronic structure calculations is
      to use auxiliary basis expansions to approximate four-center integrals in terms
      of two- and three-center integrals, usually by using the variationally optimum
      Coulomb metric to determine the expansion coefficients. However, the long-range
      decay behavior of the auxiliary basis expansion coefficients has not been
      characterized. We find that this decay can be surprisingly slow. Numerical
      experiments on linear alkanes and a toy model both show that the decay can be as
      slow as 1/r in the distance between the auxiliary function and the fitted charge
      distribution. The Coulomb metric fitting equations also involve divergent matrix
      elements for extended systems treated with periodic boundary conditions. An
      attenuated Coulomb metric that is short-range can eliminate these oddities
      without substantially degrading calculated relative energies. The sparsity of the
      fit coefficients is assessed on simple hydrocarbon molecules and shows quite
      early onset of linear growth in the number of significant coefficients with
      system size using the attenuated Coulomb metric. Hence it is possible to design
      linear scaling auxiliary basis methods without additional approximations to treat
      large systems.

PMID- 15845766
TI  - A positive feedback vector for identification of nucleotide sequences that
      enhance translation.
AB  - In earlier studies, we identified short (6- to 22-nt) sequences that functioned
      as internal ribosome entry sites (IRESes) and enhanced translation. The size of
      these IRES elements suggested that they might be prevalent within the messenger
      population and that individual elements might affect the translation of different
      groups of mRNAs. To begin to assess the number of different IRES elements in
      mammalian cells, we have developed a powerful method that uses a positive
      feedback mechanism to amplify the activities of individual IRES elements. This
      method uses a vector that encodes a dicistronic mRNA with a reporter gene
      (Renilla luciferase or the EGFP) as the first cistron and the yeast Gal4/viral
      protein 16 (VP16) transcription factor as the second cistron. Transcription of
      this mRNA is driven by a minimal promoter containing four copies of the Gal4
      upstream activation sequence. In this method, the presence of an IRES in the
      intercistronic region facilitates the translation of Gal4/VP16, which binds to
      the upstream activation sequences and triggers a positive feedback loop that
      escalates the production of dicistronic mRNA and Gal4/VP16. A corresponding
      increase in the translation of the first cistron (luciferase or EGFP) is
      monitored either by measuring luciferase activity or by using FACS. The latter
      enables IRES-positive cells to be isolated. We present tests of the feedback
      mechanism by using an IRES module from Gtx homeodomain mRNA and an IRES from
      hepatitis C virus and demonstrate the utility of this vector system for the
      screening, identification, and analysis of IRES elements.

PMID- 15845768
TI  - Phosphorylation of a UDP-glucuronosyltransferase regulates substrate specificity.
AB  - UDP-glucuronosyltransferase (UGT) isozymes catalyze detoxification of numerous
      chemical toxins present in our daily diet and environment by conjugation to
      glucuronic acid. The special properties and enzymatic mechanism(s) that enable
      endoplasmic reticulum-bound UGT isozymes to convert innumerable structurally
      diverse lipophiles to excretable glucuronides are unknown. Inhibition of cellular
      UGT1A7 and UGT1A10 activities and of [33P]orthophosphate incorporation into
      immunoprecipitable proteins after exposure to curcumin or calphostin-C indicated
      that the isozymes are phosphorylated. Furthermore, inhibition of UGT
      phosphorylation and activity by treatment with PKCepsilon-specific inhibitor
      peptide supported PKC involvement. Co-immunoprecipitation, colocalization by
      means of immunofluorescence, and cross-linking studies of PKCepsilon and
      UGT1A7His revealed that the proteins reside within 11.4 angstroms of each other.
      Moreover, mutation of three PKC sites in each UGT isozyme demonstrated that
      T73A/G and T202A/G caused null activity, whereas S432G-UGT1A7 caused a major
      shift of its pH-8.5 optimum to 6.4 with new substrate selections, including
      17beta-estradiol. S432G-UGT1A10 exhibited a minor pH shift without substrate
      alterations. PKCepsilon involvement was confirmed by the demonstration that
      PKCepsilon overexpression enhanced activity of UGT1A7 but not of its S432 mutant
      and the conversion of 17beta-[14C]estradiol by S432G-UGT1A7 but not by UGT1A7.
      Consistent with these observations, treatment of UGT1A7-transfected cells with
      PKCepsilon-specific inhibitor peptide or general PKC inhibitors increased 17beta
      estradiol catalysis between 5- and 11-fold, with parallel decreases in
      phosphoserine-432. Here, we report a mechanism involving PKC-mediated
      phosphorylation of UGT such that phosphoserine/threonine regulates substrate
      specificity in response to chemical exposures, which possibly confers survival
      benefit.

PMID- 15845769
TI  - Temporal profile of replication of human chromosomes.
AB  - Chromosomes in human cancer cells are expected to initiate replication from
      predictably localized origins, firing reproducibly at discrete times in S phase.
      Replication products obtained from HeLa cells at different stages of S phase were
      hybridized to cDNA and genome tiling oligonucleotide microarrays to determine the
      temporal profile of replication of human chromosomes on a genome-wide scale.
      About 1,000 genes and chromosomal segments were identified as sites containing
      efficient origins that fire reproducibly. Early replication was correlated with
      high gene density. An acute transition of gene density from early to late
      replicating areas suggests that discrete chromatin states dictate early versus
      late replication. Surprisingly, at least 60% of the interrogated chromosomal
      segments replicate equally in all quarters of S phase, suggesting that large
      stretches of chromosomes are replicated by inefficient, variably located and
      asynchronous origins and forks, producing a pan-S phase pattern of replication.
      Thus, at least for aneuploid cancer cells, a typical discrete time of replication
      in S phase is not seen for large segments of the chromosomes.

PMID- 15845771
TI  - Beta-TrCP recognizes a previously undescribed nonphosphorylated destruction motif
      in Cdc25A and Cdc25B phosphatases.
AB  - Beta-TrCP, the F-box protein of the SCF(beta-TrCP) ubiquitin ligase (SCF,
      Skp1/Cul1/F-box protein), recognizes the doubly phosphorylated DSG motif
      (DpSGPhiXpS) in various SCF(beta-TrCP) target proteins. The Cdc25A phosphatase, a
      key cell-cycle regulator in vertebrate cells, undergoes a rapid ubiquitin
      dependent degradation in response to genotoxic stress. Beta-TrCP binds to the DSG
      motif of human Cdc25A in a manner dependent on Chk1 and other unknown kinases.
      However, Xenopus Cdc25A does not have a DSG motif at the corresponding site of
      human Cdc25A. Here, we report that both Xenopus Cdc25A and human Cdc25A have a
      previously undescribed nonphosphorylated DDG motif (DDGPhiXD) for recognition by
      beta-TrCP. When analyzed by using Xenopus eggs, the binding of beta-TrCP to the
      DDG motif is essential for the Chk1-induced ubiquitination and degradation of
      Xenopus Cdc25A and also plays a role in the degradation of human Cdc25A. The DDG
      motif also exists in human Cdc25B phosphatase (another key cell-cycle regulator),
      binds beta-TrCP strongly, and is essential for the ubiquitination and degradation
      of the (labile) phosphatase in normal conditions. We provide strong evidence
      that, in both Cdc25A and Cdc25B, the binding (efficiency) of beta-TrCP to the DDG
      motif is regulated by nearby residues, while ubiquitination is regulated by other
      events in addition to the beta-TrCP binding. Finally, our additional data suggest
      that beta-TrCP may recognize nonphosphorylated DDG-like motifs in many other
      proteins, including X11L (a putative suppressor of beta-amyloid production) and
      hnRNP-U (a pseudosubstrate of SCF(beta-TrCP)).

PMID- 15845772
TI  - Exercise-induced intrapulmonary shunting of venous gas emboli does not occur
      after open-sea diving.
AB  - Paradoxical arterializations of venous gas emboli can lead to neurological damage
      after diving with compressed air. Recently, significant exercise-induced
      intrapulmonary anatomical shunts have been reported in healthy humans that result
      in widening of alveolar-to-arterial oxygen gradient. The aim of this study was to
      examine whether intrapulmonary shunts can be found following strenuous exercise
      after diving and, if so, whether exercise should be avoided during that period.
      Eleven healthy, military male divers performed an open-sea dive to 30 m breathing
      air, remaining at pressure for 30 min. During the bottom phase of the dive,
      subjects performed mild exercise at approximately 30% of their maximal oxygen
      uptake. The ascent rate was 9 m/min. Each diver performed graded upright cycle
      ergometry up to 80% of the maximal oxygen uptake 40 min after the dive.
      Monitoring of venous gas emboli was performed in both the right and left heart
      with an ultrasonic scanner every 20 min for 60 min after reaching the surface
      pressure during supine rest and following two coughs. The diving profile used in
      this study produced significant amounts of venous bubbles. No evidence of
      intrapulmonary shunting was found in any subject during either supine resting
      posture or any exercise grade. Also, short strenuous exercise after the dive did
      not result in delayed-onset decompression sickness in any subject, but studies
      with a greater number of participants are needed to confirm whether divers should
      be allowed to exercise after diving.

PMID- 15845774
TI  - Spinal reflexes and coactivation of ankle muscles during a submaximal fatiguing
      contraction.
AB  - This study examined the involvement of spinal mechanisms in the control of
      coactivation during a sustained contraction of the ankle dorsiflexors at 50% of
      maximal voluntary contraction. Changes in the surface electromyogram (EMG) of the
      tibialis anterior and of two antagonist muscles, the soleus and lateral
      gastrocnemius, were investigated during and after the fatigue task. Concurrently,
      the compound action potential (M-wave) and the Hoffmann reflex of the soleus and
      lateral gastrocnemius were recorded. The results showed that the torque of the
      ankle dorsiflexors and the average EMG of the tibialis anterior during maximal
      voluntary contraction declined by 40.9 +/- 17.7% (mean +/- SD; P < 0.01) and 37.0
      +/- 19.9% (P < 0.01), respectively, at task failure. During the submaximal
      fatiguing contraction, the average EMG of both the agonist and antagonist muscles
      increased, leading to a nearly constant ratio at the end of the contraction when
      normalized to postfatigue values. In contrast to the monotonic increase in
      average EMG of the antagonist muscles, the excitability of their spinal reflex
      pathways exhibited a biphasic modulation. The amplitude of the Hoffman reflexes
      in the soleus and lateral gastrocnemius increased to 147.5 +/- 52.9% (P < 0.05)
      and 166.7 +/- 74.9% (P < 0.01), respectively, during the first 20% of the
      contraction and then subsequently declined to 66.3 +/- 44.8 and 74.4 +/- 44.2% of
      their initial values. In conclusion, the results show that antagonist
      coactivation did not contribute to task failure. The different changes in
      voluntary EMG activity and spinal reflex excitability in the antagonist muscles
      during the fatiguing contraction support the concept that the level of
      coactivation is controlled by supraspinal rather than spinal mechanisms. The
      findings indicate, however, that antagonist coactivation cannot simply be
      mediated by a central descending "common drive" to the motor neuron pools of the
      agonist-antagonist muscle pairs. Rather, they suggest a more subtle regulation of
      the drive, possibly through presynaptic mechanisms, to the motoneurons that
      innervate the antagonist muscles.

PMID- 15845773
TI  - Advancing age alters rapid and spontaneous refilling of caffeine-sensitive
      calcium stores in sympathetic superior cervical ganglion cells.
AB  - Intracellular calcium concentration ([Ca2+]i) release from smooth endoplasmic
      reticulum (SER) stores plays an important role in cell signaling. These stores
      are rapidly refilled via influx through voltage-gated calcium channels or
      spontaneously via store-operated calcium channels and subsequent pumping by SER
      Ca2+-ATPases. We measured [Ca2+]i transients in isolated fura 2-loaded superior
      cervical ganglion cells from 6-, 12-, 20-, and 24-mo-old Fischer 344 rats. For
      rapid refilling, [Ca2+]i transients were elicited by a 1) 5-s exposure to K+, 2)
      caffeine to release Ca2+ from SER stores, 3) K+ to refill SER Ca2+ stores, and 4)
      caffeine. The percent difference between the peak and rate of rise of the first
      and second caffeine-evoked [Ca2+]i transient significantly declined over the age
      range of 12-24 mo. To estimate spontaneous refilling, cells were depolarized for
      5 s with 68 mM K+ (control), followed by a 10-s exposure to 10 mM caffeine
      "conditioning stimulus" to deplete [Ca2+]i stores. Caffeine was then rapidly
      applied for 5 s at defined intervals from 60 to 300 s. Integrated caffeine-evoked
      [Ca2+]i transients were measured and plotted as a percentage of the K+ response
      vs. time. The derivative of the refilling time curves significantly declined over
      the age range from 12-24 mo. Overall, these data suggest that the ability of
      superior cervical ganglion cells to sustain release of [Ca2+]i following rapid or
      spontaneous refilling declines with advancing age. Compromised ability to sustain
      calcium signaling may possibly alter the overall function of adrenergic neurons
      innervating the cerebrovasculature.

PMID- 15845775
TI  - Effects of gravity and blood volume shifts on cardiogenic oscillations in
      respired gas.
AB  - During the cardiac cycle, cardiogenic oscillations of expired gas (x)
      concentrations (COS([x])) are generated. At the same time, there are heart
      synchronous cardiogenic oscillations of airway flow (COS(flow)), where inflow
      occurs during systole. We hypothesized that both phenomena, although primarily
      generated by the heartbeat, would react differently to the cephalad blood shift
      caused by inflation of an anti-gravity (anti-G) suit and to changes in gravity.
      Twelve seated subjects performed a rebreathing-breath-holding-expiration maneuver
      with a gas mixture containing O2 and He at normal (1 G) and moderately increased
      gravity (2 G); an anti-G suit was inflated to 85 mmHg in each condition. When the
      anti-G suit was inflated, COS(flow) amplitude increased (P = 0.0028) at 1 G to
      186% of the control value without inflation (1-G control) and at 2 G to 203% of
      the control value without inflation (2-G control). In contrast, the amplitude of
      COS of the concentration of the blood-soluble gas O2 (COS([O2/He])), an index of
      the differences in pulmonary perfusion between lung units, declined to 75% of the
      1-G control value and to 74% of the 2-G control value (P = 0.0030). There were no
      significant changes in COS(flow) or COS([O2/He]) amplitudes with gravity. We
      conclude that the heart-synchronous mechanical agitation of the lungs, as
      expressed by COS(flow), is highly dependent on peripheral-to-central blood
      shifts. In contrast, COS([blood-soluble gas]) appears relatively independent of
      this mechanical agitation and seems to be determined mainly by differences in
      intrapulmonary perfusion.

PMID- 15845776
TI  - Muscle-tendon interaction and elastic energy usage in human walking.
AB  - The present study was designed to explore how the interaction between the
      fascicles and tendinous tissues is involved in storage and utilization of elastic
      energy during human walking. Eight male subjects walked with a natural cadence
      (1.4 +/- 0.1 m/s) on a 10-m-long force plate system. In vivo techniques were
      employed to record the Achilles tendon force and to scan real-time fascicle
      lengths for two muscles (medial gastrocnemius and soleus). The results showed
      that tendinous tissues of both medial gastrocnemius and soleus muscles lengthened
      slowly throughout the single-stance phase and then recoiled rapidly close to the
      end of the ground contact. However, the fascicle length changes demonstrated
      different patterns and amplitudes between two muscles. The medial gastrocnemius
      fascicles were stretched during the early single-stance phase and then remained
      isometrically during the late-stance phase. In contrast, the soleus fascicles
      were lengthened until the end of the single-stance phase. These findings suggest
      that the elastic recoil takes place not as a spring-like bouncing but as a
      catapult action in natural human walking. The interaction between the muscle
      fascicles and tendinous tissues plays an important role in the process of release
      of elastic energy, although the leg muscles, which are commonly accepted as
      synergists, do not have similar mechanical behavior of fascicles in this catapult
      action.

PMID- 15845777
TI  - Acute hypoosmolality attenuates the suppression of cutaneous vasodilation with
      increased exercise intensity.
AB  - We examined the hypothesis that elevation of the body core temperature threshold
      for forearm skin vasodilation (TH(FVC)) with increased exercise intensity is
      partially caused by concomitantly increased plasma osmolality (P(osmol)). Eight
      young male subjects, wearing a body suit perfused with warm water to maintain the
      mean skin temperature at 34 +/- 1 degree C (ranges), performed 20-min cycle
      ergometer exercise at 30% peak aerobic power (VO2(peak)) under isoosmotic
      conditions (C), and at 65% VO2(peak) under isoosmotic (H(EX)I(OS)) and
      hypoosmotic (H(EX)L(OS)) conditions. In H(EX)L(OS), hypoosmolality was attained
      by hypotonic saline infusion with DDAVP, a V2 agonist, before exercise. P(osmol)
      (mosmol/kg H2O) increased after the start of exercise in both H(EX) trials (P <
      0.01) but not in C. The average P(osmol) at 5 and 10 min in H(EX)I(OS) was higher
      than in C (P < 0.01), whereas that in H(EX)L(OS) was lower than in H(EX)I(OS) (P
      < 0.01). The change in TH(FVC) was proportional to that in P(osmol) in every
      subject for three trials. The change in TH(FVC) per unit change in P(osmol)
      (deltaTH(FVC)/deltaP(osmol), degrees C x mosmol(-1) x kg H2O(-1)) was 0.064 +/-
      0.012 when exercise intensity increased from C to H(EX)I(OS), similar to 0.086 +/
      0.020 when P(osmol) decreased from H(EX)I(OS) to H(EX)L(OS) (P > 0.1). Moreover,
      there were no significant differences in plasma volume, heart rate, mean arterial
      pressure, and plasma lactate concentration around TH(FVC) between H(EX)I(OS) and
      H(EX)L(OS) (P > 0.1). Thus the increase in TH(FVC) due to increased exercise
      intensity was at least partially explained by the concomitantly increased
      P(osmol).

PMID- 15845778
TI  - Airway smooth muscle tone modulates mechanically induced cytoskeletal stiffening
      and remodeling.
AB  - The application of mechanical stresses to the airway smooth muscle (ASM) cell
      causes time-dependent cytoskeletal stiffening and remodeling (Deng L, Fairbank
      NJ, Fabry B, Smith PG, and Maksym GN. Am J Physiol Cell Physiol 287: C440-C448,
      2004). We investigated here the extent to which these behaviors are modulated by
      the state of cell activation (tone). Localized mechanical stress was applied to
      the ASM cell in culture via oscillating beads (4.5 mum) that were tightly bound
      to the actin cytoskeleton (CSK). Tone was reduced from baseline level using a
      panel of relaxant agonists (10(-3) M dibutyryl cAMP, 10(-4) M forskolin, or 10(
      6) M formoterol). To assess functional changes, we measured cell stiffness (G')
      using optical magnetic twisting cytometry, and to assess structural changes of
      the CSK we measured actin accumulation in the neighborhood of the bead. Applied
      mechanical stress caused a twofold increase in G' at 120 min. After cessation of
      applied stress, G' diminished only 24 +/- 6% (mean +/- SE) at 1 h, leaving
      substantial residual effects that were largely irreversible. However, applied
      stress-induced stiffening could be prevented by ablation of tone. Ablation of
      tone also inhibited the amount of actin accumulation induced by applied
      mechanical stress (P < 0.05). Thus the greater the contractile tone, the greater
      was applied stress-induced CSK stiffening and remodeling. As regards pathobiology
      of asthma, this suggests a maladaptive positive feedback in which tone
      potentiates ASM remodeling and stiffening that further increases stress and
      possibly leads to worsening airway function.

PMID- 15845779
TI  - In vitro interaction of micafungin with conventional and new antifungals against
      clinical isolates of Trichosporon, Sporobolomyces and Rhodotorula.
AB  - OBJECTIVES: The infections caused by basidiomycetous yeasts are often difficult
      to resolve. Combined therapy might be useful in those severe cases where a
      monotherapy was ineffective. The aim of this study was to evaluate the in vitro
      activity of combinations of micafungin with amphotericin B or fluconazole,
      itraconazole, voriconazole and ravuconazole against isolates of Trichosporon,
      Rhodotorula and Sporobolomyces. METHODS: Twenty-seven clinical isolates were
      tested, i.e. 10 of Trichosporon asahii, two of Trichosporon mucoides, five of
      Sporobolomyces salmonicolor and 10 of Rhodotorula glutinis. Drug interactions
      were assessed by the chequerboard technique using the NCCLS microdilution method
      (M27-A2). The fractional inhibitory concentration index (FICI) was used to
      classify drug interactions. Results were interpreted as follows: synergy (FICI <
      or =0.5), no interaction (FICI >0.5 and < or =4.0), or antagonism (FICI >4.0).
      RESULTS: Micafungin combined with amphotericin B showed the highest percentage of
      synergic interactions (78%) followed by micafungin/ravuconazole and
      micafungin/itraconazole (48% for each), and micafungin/fluconazole and
      micafungin/voriconazole (34% for each). Antagonism was not observed in any case.
      CONCLUSIONS: Some of the combinations tested, especially micafungin/amphotericin
      B, have potential for the treatment of basidiomycetous yeast infections.

PMID- 15845780
TI  - A 6 week course of azithromycin treatment has no beneficial effect on
      atherosclerotic lesion development in apolipoprotein E-deficient mice chronically
      infected with Chlamydia pneumoniae.
AB  - OBJECTIVES: To evaluate whether antimicrobial chemotherapy prevents acceleration
      of atherosclerotic lesion development induced by infection with Chlamydia
      pneumoniae. METHODS: ApoE-deficient mice which develop hyperlipidaemia and
      atherosclerosis spontaneously were inoculated intranasally with C. pneumoniae.
      Animals were treated with azithromycin for 6 weeks after the third inoculation
      and the atherosclerotic lesion areas in the aortic sinus were measured by
      computer-assisted morphometry. RESULTS: At 12 weeks post-infection, infected
      untreated animals developed significantly larger lesion areas compared with sham
      inoculated controls (8.7 x 10(4)+/-2.3 x 10(4) microm(2) versus 5.6 x 10(4)+/-2.4
      x 10(4) microm(2)). However, there were no differences in lesion size of infected
      mice treated with azithromycin in comparison with untreated infected controls
      (11.0 x 10(4)+/-3.0 x 10(4) microm(2) versus 8.7 x 10(4)+/-2.3 x 10(4)
      microm(2)). CONCLUSIONS: Antibiotic treatment against C. pneumoniae has no
      beneficial effects on hyperlipidaemia-induced atherosclerosis accelerated by C.
      pneumoniae in a mouse model.

PMID- 15845781
TI  - Drug resistance and antiretroviral drug development.
AB  - As more drugs for treating HIV have become available, drug resistance profiles
      within antiretroviral drug classes have become increasingly important for
      researchers developing new drugs and for clinicians integrating new drugs into
      their clinical practice. In vitro passage experiments and comprehensive
      phenotypic susceptibility testing are used for the pre-clinical evaluation of
      drug resistance. Clinical studies are required, however, to delineate the full
      spectrum of mutations responsible for resistance to a new drug and to identify
      the settings in which a new drug is likely to be most useful for salvage therapy.

PMID- 15845783
TI  - Squalene epoxidase encoded by ERG1 affects morphogenesis and drug
      susceptibilities of Candida albicans.
AB  - OBJECTIVES: Functional characterization of the erg1 mutant of ergosterol
      biosynthesis of Candida albicans. METHODS: We disrupted the ERG1 gene of C.
      albicans, which encodes squalene epoxidase (EC 1.14.99.7). Since the disruption
      of both alleles of ERG1 was lethal, the second allele of a heterozygous
      disruptant was placed under the control of a regulable promoter, MET3p, which is
      repressed by methionine and cysteine. RESULTS: The reverse-phase HPLC analysis of
      sterol, extracted from the conditional mutant strain, showed a total lack of
      ergosterol and instead accumulation of squalene. This imbalance in sterol
      composition led to defects in growth and increased susceptibilities to drugs
      including fluconazole, ketoconazole, cycloheximide, nystatin, amphotericin B and
      terbinafine. Reduced drug efflux activity of the erg1 mutant was associated with
      poor surface localization of Cdr1p, suggesting that enhanced passive diffusion
      and reduced efflux mediated by the ABC (ATP binding cassette) transporter Cdr1p
      increases drug susceptibility. Additionally, conditional erg1 mutant strains were
      unable to form hyphae in various media. CONCLUSIONS: Taken together, our results
      demonstrate that the absence of ergosterol, which is one of the constituents of
      membrane microdomains (rafts), has a direct effect on drug susceptibility and
      morphogenesis of C. albicans.

PMID- 15845784
TI  - Successful oral pristinamycin therapy for osteoarticular infections due to
      methicillin-resistant Staphylococcus aureus (MRSA) and other Staphylococcus spp.
AB  - OBJECTIVES: Oral treatment regimens for multiresistant methicillin-resistant
      Staphylococcus aureus (MRSA) infections are limited. In Australia, rifampicin
      plus fusidic acid is the usual treatment regimen following glycopeptide therapy
      but many patients are intolerant of this; some isolates are resistant; new
      oxazolidinones are expensive for routine use. Pristinamycin is a possible
      alternative and we report our experience with this agent. METHODS: The Department
      of Microbiology and Infectious Diseases, South Western Area Pathology Service
      treats patients drawn from the South Western Sydney Area Health Service that
      houses approximately 800,000 people and contains approximately 2000 acute care
      public hospital beds. Patients prescribed pristinamycin between 1 September 2000
      and 31 January 2000 were identified from hospital pharmacy records. A
      retrospective chart review was performed. Accepted clinical definitions of
      osteomyelitis and septic arthritis were used. RESULTS: Twenty-seven patients were
      identified with osteoarticular infections. Twenty-four cases involved
      Staphylococcus aureus (multiresistant MRSA in 21 cases); three involved
      Staphylococcus epidermidis sensu stricto; four cases involved multiple organisms.
      Nineteen cases received pristinamycin monotherapy; the others received various
      combinations (fusidic acid with five; other antibiotics with three). Therapy was
      generally well tolerated; no haematological or biochemical toxicity was detected.
      Seven patients had minor gastrointestinal disturbance; and one developed rash.
      Four patients required dose reduction. Only four patients ceased pristinamycin
      due to intolerance. Treatment outcome was evaluated in 23 cases; cure was
      effected in 16 cases, five were successfully suppressed and two failed. There
      were no deaths. CONCLUSIONS: Oral pristinamycin is well tolerated and an
      important additional agent to treat osteoarticular infections with multiresistant
      MRSA and other staphylococci.

PMID- 15845785
TI  - Limited development and progression of resistance of HIV-1 to the nucleoside
      analogue reverse transcriptase inhibitor lamivudine in human primary macrophages.
AB  - OBJECTIVES: The aim of this study was to investigate the development and
      progression of phenotypic resistance to the HIV-1-reverse transcriptase (RT)
      inhibitor lamivudine, and genotypic variations of HIV-1-RT occurring under
      lamivudine treatment in HIV-1-infected human primary monocytes-macrophages (M/M).
      METHODS: Cellular passages in the presence of lamivudine were performed every 2
      weeks by transferring supernatants of infected M/M to fresh M/M. A fitness assay
      using wild-type virus and a lamivudine-resistant HIV-1 virus (harbouring the
      M184V RT mutation) was performed in peripheral blood mononuclear cells. Culture
      supernatants were tested for p24 antigen production and RT activity. The M184V RT
      mutant virus was obtained by site-directed mutagenesis on a CCR5-using HIV-1
      backbone. RESULTS: The mutagenized M184V RT virus showed full resistance to
      lamivudine in M/M. However, no detectable phenotypic and genotypic resistance
      (neither virus breakthrough, nor RT resistance-related mutations) developed in
      M/M infected by HIV-1 and cultured for up to seven passages in vitro (i.e. 105
      days). This inefficiency of M/M to develop M184V RT mutated virus is tightly
      related to the low 2'-deoxynucleotide (dNTP) pool in such cells, which in turn
      decreases the kinetics of HIV-1-RT. Despite this, the M184V RT mutant virus
      replicates in M/M, although with a 30% decreased efficiency compared with the
      wild-type. CONCLUSIONS: Our results show that the chances of development of
      resistance are far lower in M/M than in lymphocytes. This underlines the
      importance and the peculiar role of M/M as reservoirs of either wild-type or
      resistant strains in human organs.

PMID- 15845786
TI  - Quantitative assessment of left ventricular function: steady-state free
      precession MR imaging with or without sensitivity encoding.
AB  - Quantitative left ventricular (LV) function was assessed with magnetic resonance
      imaging in 20 patients by using standard multisection multiphase steady-state
      free precession (SSFP) imaging and sensitivity encoding (SENSE)-accelerated cine
      SSFP imaging with identical spatial, contrast, and temporal resolution. The local
      institutional review board approved the protocol, and all patients gave signed
      informed consent prior to imaging. The study complied with the Health Insurance
      Portability and Accountability Act. Results of Bland-Altman analysis showed that
      both techniques produced similar estimates of LV ejection fraction, LV mass, and
      blood-to-muscle contrast and demonstrated minimal interobserver variability. The
      authors showed that it is possible, by combining SENSE with cine SSFP imaging, to
      reduce acquisition time by 50% without compromising spatial resolution, temporal
      resolution, or blood-to-muscle contrast-to-noise ratio compared with those
      achieved by using SSFP imaging without SENSE for quantitative LV function
      assessment.

PMID- 15845787
TI  - Digital slot-scan charge-coupled device radiography versus AMBER and Bucky screen
      film radiography: comparison of image quality in a phantom study.
AB  - PURPOSE: To evaluate the image quality and performance of a chest digital
      radiography system and to compare this with the image quality and performance of
      advanced multiple-beam equalization radiography (AMBER) and Bucky screen-film
      radiography systems. MATERIALS AND METHODS: The chest digital radiography system
      is a digital charge-coupled device (CCD) chest imaging unit that uses slot-scan
      technology. A contrast-detail test object was used in combination with a phantom
      that simulates the primary and scatter transmission for the lungs and
      mediastinum. Twelve phantom images were obtained with each modality (ie, CCD
      digital radiography and AMBER and Bucky screen-film radiography) and were judged
      by six observers. CCD digital radiography soft-copy reading was compared with
      AMBER hard-copy reading. To measure image quality, contrast-detail curves were
      constructed from the observer data. The Wilcoxon signed rank test was used for
      statistical analysis. RESULTS: For the lung configuration, contrast-detail curves
      showed lower threshold depth for hard-copy images obtained with CCD digital
      radiography than for those obtained with Bucky screen-film radiography. For hard
      copy images, the difference between contrast-detail curves for CCD digital
      radiography and those for Bucky screen-film radiography was statistically
      significant (P < .006). No significant difference was found between CCD digital
      radiography and AMBER for hard-copy images obtained in either the lung or
      mediastinum configuration. For the lung configuration, a lower threshold depth
      was observed for CCD digital radiography soft-copy reading than for AMBER hard
      copy reading, with significantly different contrast-detail curves for CCD digital
      radiography soft copy and AMBER hard copy (P < .006). No significant difference
      was found between either system for the mediastinum configuration. CONCLUSION:
      Contrast-detail curves indicate that image quality for the CCD chest system
      provides a digital alternative to AMBER and Bucky screen-film radiography.

PMID- 15845788
TI  - Iron oxide nanoparticle-labeled rat smooth muscle cells: cardiac MR imaging for
      cell graft monitoring and quantitation.
AB  - PURPOSE: To perform a quantitative analysis of anionic maghemite nanoparticle
      labeled cells in vitro and determine the effect of labeling on signal intensity
      at magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study was approved
      by the institutional animal care and use committee at Hopital Bichat. In vitro
      cell proliferation, iron content per cell, and MR signal intensity of cells were
      measured in agarose phantoms for 0-14 days of culture after labeling of rat
      smooth muscle cells with anionic maghemite nanoparticles. Next, iron oxide
      labeled smooth muscle cells were injected into healthy hearts and hearts with
      ischemic injury in seven live Fisher rats. Ex vivo MR imaging experiments in
      excised hearts 2 and 48 hours after injection were performed with a 1.5-T medical
      imaging system by using T2-weighted gradient-echo and spin-echo sequences.
      Histologic sections were obtained after MR imaging. Correlation analyses between
      division factor of iron load and cell amplification factor and between 1/T2 and
      number of labeled cells or number of days in culture were performed by using
      linear regression. RESULTS: Viability of smooth muscle cells was not affected by
      magnetic labeling. Transmission electron micrographs of cells revealed the
      presence of iron oxide nanoparticles in vesicles up to day 14 of culture.
      Intracellular iron concentration decreased in parallel with cell division (r2 =
      0.99) and was correlated with MR signal intensity (r2 = 0.95). T2*-weighted MR
      images of excised rat hearts showed hypointense signal in myocardium at 2 and 48
      hours after local injection of labeled cells. Subsequent histologic staining
      evidenced iron oxide nanoparticles within cells and confirmed the presence of the
      original cells at 2 and 48 hours after implantation. CONCLUSION: Magnetic
      labeling of smooth muscle cells with anionic maghemite nanoparticles allows
      detection of cells with MR imaging after local transplantation in the heart.

PMID- 15845789
TI  - Fetal lung-to-liver signal intensity ratio at MR imaging: development of a normal
      scale and possible role in predicting pulmonary hypoplasia in utero.
AB  - PURPOSE: To define retrospectively a normal range for lung-to-liver signal
      intensity ratio (LLSIR) in fetuses of 16-40 weeks gestation by using half-Fourier
      single-shot turbo spin-echo magnetic resonance (MR) imaging. MATERIALS AND
      METHODS: Approval from the regional ethics review board for retrospective
      evaluation was obtained, and informed consent was waived. Retrospective analysis
      and follow-up of 157 pregnant women who underwent MR imaging over the past 4
      years were performed. Seventy-four fetuses were subsequently identified as having
      clinically normal lung function or normal lung morphologic features at autopsy. A
      total of 141 normal lungs were analyzed, and the LLSIR was calculated from images
      on an MR workstation. A mixed-effects statistical model was applied, and 95%
      prediction intervals were calculated. Ten fetuses with hypoplastic lungs at
      autopsy were also evaluated. RESULTS: Plotting LLSIR against gestational age
      demonstrated that, according to the fitted mean curve, the signal intensity ratio
      was higher with more advanced gestational age. Statistical modeling suggests a
      quadratic relationship between gestational age and LLSIR. For fetuses in the
      normal population, the LLSIR ranged from 1.52 at 21 weeks gestation to 4.31 at 34
      weeks gestation. For all hypoplastic lungs in fetuses at or beyond 25 weeks
      gestation, the LLSIR was outside the lower bound of the 95% prediction interval
      for the normal population. The distinction between hypoplastic lungs and normal
      lungs at less than 25 weeks gestation is less definitive. CONCLUSION: This study
      provides a normal scale with a 95% prediction interval for LLSIR.

PMID- 15845790
TI  - Percutaneous transhepatic balloon dilation of portal venous stenosis in patients
      with living donor liver transplantation.
AB  - PURPOSE: To retrospectively evaluate the long-term effectiveness of percutaneous
      transhepatic balloon dilation of portal venous stenosis in patients who have
      undergone living donor liver transplantation. MATERIALS AND METHODS:
      Institutional review board approval and informed consent were not required. From
      June 1996 to August 2003, obstructed portal venous blood flow was diagnosed in 45
      patients (21 male, 24 female) with a history of living donor liver
      transplantation; patients ranged in age from 9 months to 61 years (mean, 9.2
      years). All stenoses occurred in the extrahepatic portal vein near the
      anastomosis of the portal vein. All dilation procedures were performed with
      percutaneous transhepatic puncture of the intrahepatic portal vein and subsequent
      balloon dilation of the stenosis. Patients who experienced recurrent stenosis
      underwent another balloon dilation session. Intravascular metallic stents were
      not deployed because of the possible need for repeated transplantation. The
      authors used paired t tests to compare patients successfully treated with one
      venoplasty procedure and those requiring repeated venoplasty, with regard to age
      and stenosis diameter percentages before and after the initial procedure.
      RESULTS: Percutaneous balloon dilation was technically successful in 35 of 45
      patients. In the remaining 10 patients, portal venous thrombotic occlusion
      precluded access to the mesenteric side of the portal vein. Twenty-five patients
      were successfully treated with a single session of balloon dilation (group 1).
      Results at follow-up ultrasonography revealed restenosis in 10 of 35 patients.
      Recurrent stenosis was resolved by means of repeated balloon dilation in nine
      patients (group 2). There were no significant differences between groups 1 and 2
      in age (P = .87) or in stenosis diameter percentages before (P = .053) or after
      (P = .95) the initial procedure. CONCLUSION: Percutaneous transhepatic balloon
      dilation seems to be an effective method for treatment of portal venous stenosis
      after living donor liver transplantation.

PMID- 15845791
TI  - Comparative scatter and dose performance of slot-scan and full-field digital
      chest radiography systems.
AB  - PURPOSE: To evaluate the scatter, dose, and effective detective quantum
      efficiency (DQE) performance of a slot-scan digital chest radiography system
      compared with that of a full-field digital radiography system. MATERIALS AND
      METHODS: Scatter fraction of a slot-scan system was measured for an
      anthropomorphic and a geometric phantom by using a posterior beam-stop technique
      at 117 and 140 kVp. Measurements were repeated with a full-field digital
      radiography system with and without a 13:1 antiscatter grid at 120 and 140 kVp.
      For both systems, the effective dose was measured on posteroanterior and lateral
      views for standard clinical techniques by using dosimeters embedded in a female
      phantom. The effective DQEs of the two systems were assessed by taking into
      account the scatter performance and the DQE of each system. The statistical
      significance of all the comparative differences was ascertained by means of t
      test analysis. RESULTS: The slot-scan system and the full-field system with grid
      yielded scatter fractions of 0.13-0.14 and 0.42-0.48 in the lungs and 0.30-0.43
      and 0.69-0.78 in the mediastinum, respectively. The sum of the effective doses
      for posteroanterior and lateral views for the slot-scan system (0.057 mSv +/-
      0.003 [+/- standard deviation]) was 34% lower than that for the full-field system
      (0.086 mSv +/- 0.001, P < .05) at their respective clinical peak voltages (140
      and 120 kVp, respectively). The effective DQE of the slot-scan system was
      equivalent to that of the full-field system in the lung region but was 37% higher
      in the dense regions (P < .05). CONCLUSION: The slot-scan design leads to marked
      scatter reduction compared with the more conventional full-field geometries with
      a grid. The improved scatter performance of a slot-scan geometry can effectively
      compensate for low DQE and lead to improved image quality.

PMID- 15845792
TI  - Diffusion-weighted MR imaging of kidneys in healthy volunteers and patients with
      parenchymal diseases: initial experience.
AB  - PURPOSE: To prospectively evaluate feasibility of diffusion-weighted (DW)
      magnetic resonance (MR) imaging in assessment of renal function in healthy
      volunteers and patients with various renal abnormalities and to prospectively
      evaluate reproducibility of DW MR imaging in volunteers. MATERIALS AND METHODS:
      Study protocol was approved by local ethics committee; informed consent was
      obtained. Eighteen healthy volunteers and 15 patients underwent transverse fat
      saturated echo-planar DW MR imaging of the kidneys during normal breathing.
      Freehand regions of interest were delineated in the cortex and medulla of the
      kidneys. The following apparent diffusion coefficient (ADC) values were
      calculated: ADC of all b values (ADC(avg)), ADC of low b values (b = 0, 50, 100
      sec/mm2; ADC(low)), and ADC of high b values (b = 500, 750, 1000 sec/mm2;
      ADC(high)). These values were calculated to differentiate influence of perfusion
      and diffusion. Reproducibility was assessed by repeating the same protocol in
      five randomly selected volunteers after 6 months. For statistical analysis,
      Student t tests were used. RESULTS: In all volunteers, ADC(avg) and ADC(high)
      were significantly higher in the cortex than in the medulla (P < .001). No
      difference between the cortex and medulla could be observed for ADC(low).
      Patients with renal failure had significantly lower ADC(avg) (P < .001, P =
      .004), ADC(low) (P = .02, P = .03), and ADC(high) (P = .02, P = .04) of cortex
      and medulla, respectively, than did volunteers. In the patient with
      pyelonephritis, all ADC values of cortex and medulla were substantially lower
      compared with the contralateral side, whereas patients with ureteral obstruction
      showed varying degrees of difference in all ADC values compared with the
      contralateral side. No statistically significant changes were found in the repeat
      study of the volunteers. CONCLUSION: DW MR imaging is feasible and reproducible
      in the assessment of renal function, as shown in our initial experience with a
      small number of patients and volunteers.

PMID- 15845793
TI  - Right ventricular dysfunction and pulmonary obstruction index at helical CT:
      prediction of clinical outcome during 3-month follow-up in patients with acute
      pulmonary embolism.
AB  - PURPOSE: To retrospectively quantify right ventricular dysfunction (RVD) and the
      pulmonary artery obstruction index at helical computed tomography (CT) on the
      basis of various criteria proposed in the literature and to assess the predictive
      value of these CT parameters for mortality within 3 months after the initial
      diagnosis of pulmonary embolism (PE). MATERIALS AND METHODS: Institutional review
      board approval was obtained, and informed consent was not required for
      retrospective study. In 120 consecutive patients (55 men, 65 women; mean age +/-
      standard deviation, 59 years +/- 18) with proved PE, two readers assessed the
      extent of RVD by quantifying the ratio of the right ventricle to left ventricle
      short-axis diameters (RV/LV) and the pulmonary artery to ascending aorta
      diameters, the shape of the interventricular septum, and the extent of
      obstruction to the pulmonary artery circulation on helical CT images, which were
      blinded for clinical outcome in consensus reading. Regression analysis was used
      to correlate these parameters with patient outcome. RESULTS: CT signs of RVD
      (RV/LV ratio, >1.0) were seen in 69 patients (57.5%). During follow-up, seven
      patients died of PE. Both the RV/LV ratio and the obstruction index were shown to
      be significant risk factors for mortality within 3 months (P = .04 and .01,
      respectively). No such relationship was found for the ratio of the pulmonary
      artery to ascending aorta diameters (P = .66) or for the shape of the
      interventricular septum (P = .20). The positive predictive value for PE-related
      mortality with an RV/LV ratio greater than 1.0 was 10.1% (95% confidence interval
      [CI]: 2.9%, 17.4%). The negative predictive value for an uneventful outcome with
      an RV/LV ratio of 1.0 or less was 100% (95% CI: 94.3%, 100%). There was a 11.2
      fold increased risk of dying of PE for patients with an obstruction index of 40%
      or higher (95% CI: 1.3, 93.6). CONCLUSION: Markers of RVD and pulmonary vascular
      obstruction, assessed with helical CT at baseline, help predict mortality during
      follow-up.

PMID- 15845794
TI  - Subclavian steal syndrome: diagnosis with perfusion metrics from contrast
      enhanced MR angiographic bolus-timing examination--initial experience.
AB  - PURPOSE: To retrospectively determine whether differential temporal changes in
      signal intensity of the vertebral arteries, measured at a bolus-timing
      examination with a test dose of a gadolinium-based contrast agent, are present in
      patients with subclavian steal syndrome. MATERIALS AND METHODS: Institutional
      review board exemption was obtained, and informed consent was not required for
      this retrospective study. The study complied with the Health Insurance
      Portability and Accountability Act. Twenty-five patients with known or clinically
      suspected atherosclerotic disease of the aortic arch and branch vessels underwent
      breath-hold contrast material-enhanced magnetic resonance (MR) angiography with
      circulation time derived from a timing examination by using a test bolus of a
      gadolinium-based contrast agent. Eight patients (three men and five women aged 54
      80 years; mean, 70 years) had subclavian stenosis or occlusion with retrograde
      vertebral artery flow confirmed with time-of-flight MR angiography, nine patients
      (eight men and one woman aged 31-91 years; mean, 70 years) had mild to severe
      ostial stenosis of a single vertebral artery, and eight patients (including four
      men and four women aged 53-86 years; mean, 73 years) had normal vertebral
      arteries. The difference in time to peak signal intensity between the right and
      left vertebral arteries was compared among the three groups by using Fisher exact
      and Cochran-Mantel-Haenszel tests. RESULTS: The delay in peak enhancement in the
      ipsilateral vertebral artery ranged from 2 to 4 seconds (mean, 2.5 seconds) in
      all eight patients with subclavian steal syndrome. In eight of nine patients with
      ostial vertebral artery stenosis and eight controls, both vertebral arteries
      filled simultaneously. The presence of unilateral delayed vertebral artery
      enhancement was significantly associated with retrograde flow in patients with
      subclavian steal syndrome, compared with patients with normal flow (P < .01) and
      those with ostial vertebral artery stenosis (P < .01). CONCLUSION: A bolus-timing
      examination performed with a test bolus of the gadolinium-based contrast agent
      via the neck vessels that demonstrates at least a 2-second delay in peak contrast
      enhancement in the right or left vertebral arteries may, in the appropriate
      clinical setting, indicate subclavian steal syndrome.

PMID- 15845795
TI  - Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and nonionic iso
      osmolar dimeric iodinated contrast media on renal tubular cells in vitro.
AB  - PURPOSE: To compare the cytotoxic effects of dimeric and monomeric iodinated
      contrast media on renal tubular cells in vitro with regard to osmolality.
      MATERIALS AND METHODS: LLC-PK1 cells were incubated with ioxithalamate, ioversol,
      iomeprol-300, iomeprol-150, iodixanol, iotrolan, and hyperosmolar mannitol
      solutions for 1-24 hours at concentrations from 18.75 to 150 mg of iodine per
      milliliter. Cytotoxic effects were assessed with 3-(4,5-dimethyl-2-thiazolyl)-2,5
      diphenyl-2H-tetrazolium bromide (MTT) assay. Data were analyzed with one-way
      analysis of variance; post hoc tests were performed. RESULTS: At equal iodine
      concentrations, ioxithalamate showed stronger cytotoxic effects than did other
      contrast media (MTT conversion for ioxithalamate was 4% vs that for ioversol of
      32%, that for iomeprol-300 of 34%, that for iodixanol of 40%, and that for
      iotrolan of 41% of undamaged control cells at 75 mg of iodine per milliliter, n =
      61-90, P < .001); there was no significant difference between low-osmolar
      monomeric and iso-osmolar dimeric contrast media (P > .05). At equal molarity,
      dimeric contrast media induced significantly stronger cytotoxic effects than did
      low-osmolar monomeric contrast media (40% for iodixanol and 41% for iotrolan vs
      64% for ioversol and 59% for iomeprol-300 at 98.5 mmol/L, n = 61-75, P < .001).
      At equimolar concentrations, both dimeric contrast media showed stronger
      cytotoxic effects than did iso-osmolar formulation of iomeprol-150 (51% for
      iodixanol and 50% for iotrolan vs 77% for iomeprol-150 at 98.5 mmol/L, n = 35-40,
      P < .001). Mannitol solutions induced weaker cytotoxic effects than did
      corresponding contrast media compounds (74% for mannitol-520 vs 34% for iomeprol
      300 and 41% for mannitol-1860 vs 4% for ioxithalamate, P < .001). CONCLUSION:
      Besides hyperosmolality, direct cytotoxic effects of contrast media molecules
      contribute to their cytotoxic effects. Results of this study indicate that
      dimeric contrast media molecules have a greater potential for cytotoxic effects
      on proximal renal tubular cells in vitro than do monomeric contrast media
      molecules.

PMID- 15845796
TI  - Gadobenate dimeglumine-enhanced MR imaging breast vascular maps: association
      between invasive cancer and ipsilateral increased vascularity.
AB  - PURPOSE: To retrospectively compare three different doses of gadobenate
      dimeglumine with a standard dose of gadopentetate dimeglumine for magnetic
      resonance (MR) imaging evaluation of breast vessels and to evaluate the accuracy
      of one-sided increased vascularity seen on gadobenate dimeglumine-enhanced MR
      images as an indicator of ipsilateral breast cancer. MATERIALS AND METHODS: The
      original study had local ethics committee approval; informed consent was obtained
      from all enrolled patients. Ninety-five patients known to have or suspected of
      having breast cancer were randomly assigned to four groups to receive gadobenate
      dimeglumine at a dose of 0.05, 0.10, or 0.20 mmol per kilogram of body weight or
      gadopentetate dimeglumine at a dose of 0.10 mmol/kg. T1-weighted gradient-echo MR
      images were acquired before and 2 minutes after intravenous contrast material
      injection. Subtracted images were used to obtain maximum intensity projections
      (MIPs). Two readers blinded to the type and dose of contrast agent administered
      scored the MIPs obtained in the dose groups for vessel number, length, and
      conspicuity from 0, which indicated absent or low breast vascularity, to 3, which
      indicated high breast vascularity. The sensitivity, specificity, accuracy,
      positive predictive value (PPV), and negative predictive value (NPV) of one-sided
      increased vascularity in association with ipsilateral malignancy for 69
      histopathologically confirmed lesions (reference standard) were determined after
      gadobenate dimeglumine-enhanced MR imaging. RESULTS: The mean MIP scores assigned
      to the gadobenate dimeglumine groups were significantly higher than those
      assigned to the gadopentetate dimeglumine group (P < or = .044). Histopathologic
      analysis revealed malignant lesions in 52 of 69 patients examined with gadobenate
      dimeglumine MR imaging: invasive ductal carcinoma in 45, invasive lobular
      carcinoma in four, and invasive mixed ductal-lobular carcinoma in three patients.
      Seventeen patients had benign lesions. Two cases of bilateral invasive cancer
      with symmetric breast vascular maps were excluded. Thus, the overall sensitivity,
      specificity, accuracy, PPV, and NPV of one-sided increased vascularity as a
      finding associated with ipsilateral malignancy were 88% (44 of 50 patients), 82%
      (14 of 17 patients), 87% (58 of 67 patients), 94% (44 of 47 patients), and 70%
      (14 of 20 patients), respectively. CONCLUSION: Gadobenate dimeglumine is
      effective for MR imaging evaluation of breast vessels at doses as low as 0.05
      mmol/kg. One-sided increased vascularity is an MR imaging finding frequently
      associated with ipsilateral invasive breast cancer.

PMID- 15845797
TI  - Safety and effectiveness of gadolinium-enhanced multi-detector row spiral CT
      angiography of the chest: preliminary results in 37 patients with
      contraindications to iodinated contrast agents.
AB  - PURPOSE: To prospectively evaluate the safety and effectiveness of gadolinium
      enhanced multi-detector row spiral computed tomographic (CT) angiography of the
      pulmonary circulation by using two gadolinium doses in patients with
      contraindications to iodinated contrast agents. MATERIALS AND METHODS: Study was
      approved by the Ethics Committee, and written informed consent was obtained.
      Thirty-seven patients (20 men, 17 women) with contraindications to iodinated
      contrast agents (allergic reactions, n = 27; impaired renal function, n = 10)
      underwent CT angiography of the pulmonary circulation in search of acute
      pulmonary embolism (n = 28) or for management of tumoral disease (n = 9). CT
      angiography was performed (a) with four-detector row (n = 19) or 16-detector row
      (n = 18) scanners; (b) at randomly assigned gadolinium doses of either 0.3 mmol
      per kilogram of body weight (n = 19) or 0.4 mmol/kg (n = 18); and (c) with a
      systematic evaluation of clinical and biologic tolerance of gadolinium.
      Comparison of percentages between group 1 and group 2 scans was performed with
      the chi2 or the Fisher exact test. An unpaired Wilcoxon rank sum test was used
      for numeric variables. P < .05 was considered to indicate a significant
      difference. RESULTS: The mean (+/- standard deviation) volume of gadopentetate
      dimeglumine administered in the overall study group was 48 mL +/- 9.6 (range, 29
      65 mL). The level of maximal enhancement in the pulmonary arteries was
      significantly higher in group 2 than in group 1 (215.8 HU +/- 95 vs 141.3 HU +/-
      44) (P = .02) and was maintained throughout the entire region of interest in a
      greater number of examinations in group 2 than in group 1 (n = 16 [89%] vs n = 2
      [10.5%]) (P < .0001). The number of diagnostic CT angiograms was significantly
      higher in group 2 than in group 1 (n = 17 [94%] vs n = 13 [68%]) (P = .007).
      Significant but transient reduction of creatinine clearance was observed in one
      patient with preexisting moderate chronic renal failure (0.3 mmol/kg gadolinium
      dose). CONCLUSION: High-quality gadolinium-enhanced CT angiograms require the use
      of 16-detector row CT technology; the doses administered did not alter the renal
      function except transiently in one patient.

PMID- 15845799
TI  - American College of Radiology clinical statement on noninvasive cardiac imaging.

PMID- 15845800
TI  - Observations on heat/humidity denaturation of enzymes in filter-paper blood spots
      from newborns.

PMID- 15845798
TI  - Image-guided tumor ablation: standardization of terminology and reporting
      criteria.
AB  - The field of interventional oncology with use of image-guided tumor ablation
      requires standardization of terminology and reporting criteria to facilitate
      effective communication of ideas and appropriate comparison between treatments
      that use different technologies, such as chemical (ethanol or acetic acid)
      ablation, and thermal therapies, such as radiofrequency, laser, microwave,
      ultrasound, and cryoablation. This document provides a framework that will
      hopefully facilitate the clearest communication between investigators and will
      provide the greatest flexibility in comparison between the many new, exciting,
      and emerging technologies. An appropriate vehicle for reporting the various
      aspects of image-guided ablation therapy, including classification of therapies
      and procedure terms, appropriate descriptors of imaging guidance, and terminology
      to define imaging and pathologic findings, are outlined. Methods for
      standardizing the reporting of follow-up findings and complications and other
      important aspects that require attention when reporting clinical results are
      addressed. It is the group's intention that adherence to the recommendations will
      facilitate achievement of the group's main objective: improved precision and
      communication in this field that lead to more accurate comparison of technologies
      and results and, ultimately, to improved patient outcomes.

PMID- 15845801
TI  - Differences and similarities between two frequently used assays for amyloid beta
      42 in cerebrospinal fluid.

PMID- 15845804
TI  - Monoclonal versus polyclonal ELISA for assessment of fecal elastase
      concentration: pitfalls of a new assay.

PMID- 15845803
TI  - Standardized approach to proteome profiling of human serum based on magnetic bead
      separation and matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - BACKGROUND: Magnetic bead purification for the analysis of low-abundance proteins
      in body fluids facilitates the identification of potential new biomarkers by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS). The aims of our study were to establish a proteome fractionation
      technique and to validate a standardized blood sampling, processing, and storage
      procedure for proteomic pattern analysis. METHODS: We used magnetic bead
      separation for proteome profiling of human blood by MALDI-TOF MS (mass range,
      1000-10,000 Da) and studied the effects on the quality and reproducibility of the
      proteome analysis of anticoagulants, blood clotting, time and temperature of
      sample storage, and the number of freeze-thaw cycles of samples. RESULTS: The
      proteome pattern of human serum was characterized by approximately 350 signals in
      the mass range of 1000-10,000 Da. The proteome profile showed time-dependent
      dynamic changes before and after centrifugation of the blood samples. Serum mass
      patterns differed between native samples and samples frozen once. The best
      reproducibility of proteomic patterns was with a single thawing of frozen serum
      samples. CONCLUSION: Application of the standardized preanalytical blood sampling
      and storage procedure in combination with magnetic bead-based fractionation
      decreases variability of proteome patterns in human serum assessed by MALDI-TOF
      MS.

PMID- 15845806
TI  - NASA redux.

PMID- 15845805
TI  - Speciation and quantification of thiols by reversed-phase chromatography coupled
      with on-line chemical vapor generation and atomic fluorescence spectrometric
      detection: method validation and preliminary application for glutathione
      measurements in human whole blood.
AB  - BACKGROUND: We developed a sensitive, specific method for the low-molecular-mass
      thiols cysteine, cysteinylglycine, glutathione, and homocysteine and validated
      the method for measurement of glutathione in blood. METHODS: The technique was
      based on reversed-phase chromatography (RPC) coupled on line with cold vapor
      generation atomic fluorescence spectrometry (CVGAFS). Thiols were derivatized
      before introduction on the column by use of a p-hydroxymercuribenzoate (PHMB)
      mercurial probe and separated as thiol-PHMB complexes on a Vydac C4 column.
      Postcolumn on-line reaction of derivatized thiols with bromine allowed rapid
      conversion of the thiol-PHMB complexes to inorganic mercury with recovery of 100
      (2)% of the sample. HgII was selectively detected by atomic fluorescence
      spectrometry in an Ar/H2 miniaturized flame after sodium borohydride reduction to
      Hg0. RESULTS: The relationship between thiol-PHMB complex concentration and peak
      area (CVGAFS signal) was linear over the concentration range 0.01-1400 micromol/L
      (injected). The detection limits were 1, 1, 0.6, and 0.8 nmol/L for cysteine,
      cysteinylglycine, homocysteine, and glutathione in the injected sample,
      respectively. The CVs for thiols were 1.5%-2.2% for calibrator solutions and 2.1%
      and 3.0% for real samples. The RPC-CVGAFS method allowed speciation of
      glutathione (reduced and oxidized) in human whole blood from healthy donors and
      from the coronary sinus of patients with idiopathic dilated cardiomyopathy during
      and after chronotropic stress. CONCLUSION: The RPC-CVGAFS method could be used to
      measure reduced and oxidized glutathione in human whole blood as disease
      biomarkers.

PMID- 15845807
TI  - Influenza. Test kit error is wake-up call for 50-year-old foe.

PMID- 15845808
TI  - Avian influenza. Outbreak in northern Vietnam baffles experts.

PMID- 15845809
TI  - U.K. science. Industry-academic drug screening plan targets CJD.

PMID- 15845810
TI  - Cosmology. Counterattack heats up dispute over 'dark energy'.

PMID- 15845811
TI  - High-energy physics. Latest data deal 'pentaquark' sightings a fresh blow.

PMID- 15845812
TI  - High-energy physics. Unspeakable state of matter starts to reveal itself-but for
      how long?

PMID- 15845814
TI  - Higher education. Bill offers break on loans to boost study of science.

PMID- 15845813
TI  - Molecular biology. Human RNA slows down a primate retrovirus.

PMID- 15845816
TI  - Climate change. Global warming skeptic argues U.S. position in suit.

PMID- 15845815
TI  - Ecology. Sucrose-free sips suit acacia ants.

PMID- 15845817
TI  - German science. Plan to boost university research caught in political crossfire.

PMID- 15845818
TI  - Gender equity: Japan mulls workforce goals for women.

PMID- 15845819
TI  - Space science. Balancing the right stuff.

PMID- 15845820
TI  - Space science. "We can do the program that the president has proposed".

PMID- 15845821
TI  - Ecosystem management. California tries to connect its scattered marine reserves.

PMID- 15845822
TI  - Infectious diseases. Crisis of confidence hampers Marburg control in Angola.

PMID- 15845823
TI  - Physical anthropology/paleoanthropology meetings. Once-balmy climate lured humans
      to England early.

PMID- 15845824
TI  - Physical anthropology/paleoanthropology meetings. Archaic genes in modern people?

PMID- 15845825
TI  - Physical anthropology/paleoanthropology meetings. Modern humans made their point.

PMID- 15845826
TI  - Physical anthropology/paleoanthropology meetings. Snapshots from the meeting.

PMID- 15845827
TI  - Evolution can't be taught in 270 minutes.

PMID- 15845828
TI  - Keeping an open mind?

PMID- 15845829
TI  - Keep censorship out of schools.

PMID- 15845830
TI  - Let students weigh the evidence.

PMID- 15845831
TI  - Don't dismiss astrobiology.

PMID- 15845832
TI  - A lupus drug and FDA approval.

PMID- 15845833
TI  - The Norwegian position on culling.

PMID- 15845834
TI  - Clarifications about teratorns.

PMID- 15845835
TI  - Comment on "Force-clamp spectroscopy monitors the folding trajectory of a single
      protein".

PMID- 15845837
TI  - Psychology. The science of child sexual abuse.

PMID- 15845838
TI  - Applied physics. How to build a superlens.

PMID- 15845839
TI  - Neuroscience. Watching single cells pay attention.

PMID- 15845840
TI  - Cell biology. A fishing buddy for hypothesis generators.

PMID- 15845841
TI  - Plant sciences. Recognition at a distance.

PMID- 15845842
TI  - Applied physics. Toward a universal memory.

PMID- 15845843
TI  - Cell biology. Guiding ATM to broken DNA.

PMID- 15845844
TI  - Transduction of receptor signals by beta-arrestins.
AB  - The transmission of extracellular signals to the interior of the cell is a
      function of plasma membrane receptors, of which the seven transmembrane receptor
      family is by far the largest and most versatile. Classically, these receptors
      stimulate heterotrimeric G proteins, which control rates of generation of
      diffusible second messengers and entry of ions at the plasma membrane. Recent
      evidence, however, indicates another previously unappreciated strategy used by
      the receptors to regulate intracellular signaling pathways. They direct the
      recruitment, activation, and scaffolding of cytoplasmic signaling complexes via
      two multifunctional adaptor and transducer molecules, beta-arrestins 1 and 2.
      This mechanism regulates aspects of cell motility, chemotaxis, apoptosis, and
      likely other cellular functions through a rapidly expanding list of signaling
      pathways.

PMID- 15845845
TI  - H2S induces a suspended animation-like state in mice.
AB  - Mammals normally maintain their core body temperature (CBT) despite changes in
      environmental temperature. Exceptions to this norm include suspended animation
      like states such as hibernation, torpor, and estivation. These states are all
      characterized by marked decreases in metabolic rate, followed by a loss of
      homeothermic control in which the animal's CBT approaches that of the
      environment. We report that hydrogen sulfide can induce a suspended animation
      like state in a nonhibernating species, the house mouse (Mus musculus). This
      state is readily reversible and does not appear to harm the animal. This suggests
      the possibility of inducing suspended animation-like states for medical
      applications.

PMID- 15845846
TI  - Solar wind origin in coronal funnels.
AB  - The origin of the solar wind in solar coronal holes has long been unclear. We
      establish that the solar wind starts flowing out of the corona at heights above
      the photosphere between 5 megameters and 20 megameters in magnetic funnels. This
      result is obtained by a correlation of the Doppler-velocity and radiance maps of
      spectral lines emitted by various ions with the force-free magnetic field as
      extrapolated from photospheric magnetograms to different altitudes. Specifically,
      we find that Ne7+ ions mostly radiate around 20 megameters, where they have
      outflow speeds of about 10 kilometers per second, whereas C3+ ions with no
      average flow speed mainly radiate around 5 megameters. Based on these results, a
      model for understanding the solar wind origin is suggested.

PMID- 15845847
TI  - Causal protein-signaling networks derived from multiparameter single-cell data.
AB  - Machine learning was applied for the automated derivation of causal influences in
      cellular signaling networks. This derivation relied on the simultaneous
      measurement of multiple phosphorylated protein and phospholipid components in
      thousands of individual primary human immune system cells. Perturbing these cells
      with molecular interventions drove the ordering of connections between pathway
      components, wherein Bayesian network computational methods automatically
      elucidated most of the traditionally reported signaling relationships and
      predicted novel interpathway network causalities, which we verified
      experimentally. Reconstruction of network models from physiologically relevant
      primary single cells might be applied to understanding native-state tissue
      signaling biology, complex drug actions, and dysfunctional signaling in diseased
      cells.

PMID- 15845848
TI  - Parallel and serial neural mechanisms for visual search in macaque area V4.
AB  - To find a target object in a crowded scene, a face in a crowd for example, the
      visual system might turn the neural representation of each object on and off in a
      serial fashion, testing each representation against a template of the target
      item. Alternatively, it might allow the processing of all objects in parallel but
      bias activity in favor of those neurons that represent critical features of the
      target, until the target emerges from the background. To test these
      possibilities, we recorded neurons in area V4 of monkeys freely scanning a
      complex array to find a target defined by color, shape, or both. Throughout the
      period of searching, neurons gave enhanced responses and synchronized their
      activity in the gamma range whenever a preferred stimulus in their receptive
      field matched a feature of the target, as predicted by parallel models. Neurons
      also gave enhanced responses to candidate targets that were selected for
      saccades, or foveation, reflecting a serial component of visual search. Thus,
      serial and parallel mechanisms of response enhancement and neural synchrony work
      together to identify objects in a scene. To find a target object in a crowded
      scene, a face in a crowd for example, the visual system might turn the neural
      representation of each object on and off in a serial fashion, testing each
      representation against a template of the target item. Alternatively, it might
      allow the processing of all objects in parallel but bias activity in favor of
      those neurons that represent critical features of the target, until the target
      emerges from the background. To test these possibilities, we recorded neurons in
      area V4 of monkeys freely scanning a complex array to find a target defined by
      color, shape, or both. Throughout the period of searching, neurons gave enhanced
      responses and synchronized their activity in the gamma range whenever a preferred
      stimulus in their receptive field matched a feature of the target, as predicted
      by parallel models. Neurons also gave enhanced responses to candidate targets
      that were selected for saccades, or foveation, reflecting a serial component of
      visual search. Thus, serial and parallel mechanisms of response enhancement and
      neural synchrony work together to identify objects in a scene.

PMID- 15845849
TI  - Sub-diffraction-limited optical imaging with a silver superlens.
AB  - Recent theory has predicted a superlens that is capable of producing sub
      diffraction-limited images. This superlens would allow the recovery of evanescent
      waves in an image via the excitation of surface plasmons. Using silver as a
      natural optical superlens, we demonstrated sub-diffraction-limited imaging with
      60-nanometer half-pitch resolution, or one-sixth of the illumination wavelength.
      By proper design of the working wavelength and the thickness of silver that
      allows access to a broad spectrum of subwavelength features, we also showed that
      arbitrary nanostructures can be imaged with good fidelity. The optical superlens
      promises exciting avenues to nanoscale optical imaging and ultrasmall
      optoelectronic devices.

PMID- 15845850
TI  - Monodisperse double emulsions generated from a microcapillary device.
AB  - Double emulsions are highly structured fluids consisting of emulsion drops that
      contain smaller droplets inside. Although double emulsions are potentially of
      commercial value, traditional fabrication by means of two emulsification steps
      leads to very ill-controlled structuring. Using a microcapillary device, we
      fabricated double emulsions that contained a single internal droplet in a core
      shell geometry. We show that the droplet size can be quantitatively predicted
      from the flow profiles of the fluids. The double emulsions were used to generate
      encapsulation structures by manipulating the properties of the fluid that makes
      up the shell. The high degree of control afforded by this method and the
      completely separate fluid streams make this a flexible and promising technique.

PMID- 15845851
TI  - Retreating glacier fronts on the Antarctic Peninsula over the past half-century.
AB  - The continued retreat of ice shelves on the Antarctic Peninsula has been widely
      attributed to recent atmospheric warming, but there is little published work
      describing changes in glacier margin positions. We present trends in 244 marine
      glacier fronts on the peninsula and associated islands over the past 61 years. Of
      these glaciers, 87% have retreated and a clear boundary between mean advance and
      retreat has migrated progressively southward. The pattern is broadly compatible
      with retreat driven by atmospheric warming, but the rapidity of the migration
      suggests that this may not be the sole driver of glacier retreat in this region.

PMID- 15845852
TI  - Warming of the Eurasian landmass is making the Arabian Sea more productive.
AB  - The recent trend of declining winter and spring snow cover over Eurasia is
      causing a land-ocean thermal gradient that is particularly favorable to stronger
      southwest (summer) monsoon winds. Since 1997, sea surface winds have been
      strengthening over the western Arabian Sea. This escalation in the intensity of
      summer monsoon winds, accompanied by enhanced upwelling and an increase of more
      than 350% in average summertime phytoplankton biomass along the coast and over
      300% offshore, raises the possibility that the current warming trend of the
      Eurasian landmass is making the Arabian Sea more productive.

PMID- 15845854
TI  - A cellular microRNA mediates antiviral defense in human cells.
AB  - In eukaryotes, 21- to 24-nucleotide-long RNAs engage in sequence-specific
      interactions that inhibit gene expression by RNA silencing. This process has
      regulatory roles involving microRNAs and, in plants and insects, it also forms
      the basis of a defense mechanism directed by small interfering RNAs that derive
      from replicative or integrated viral genomes. We show that a cellular microRNA
      effectively restricts the accumulation of the retrovirus primate foamy virus type
      1 (PFV-1) in human cells. PFV-1 also encodes a protein, Tas, that suppresses
      microRNA-directed functions in mammalian cells and displays cross-kingdom
      antisilencing activities. Therefore, through fortuitous recognition of foreign
      nucleic acids, cellular microRNAs have direct antiviral effects in addition to
      their regulatory functions.

PMID- 15845855
TI  - Postsecretory hydrolysis of nectar sucrose and specialization in ant/plant
      mutualism.
AB  - Obligate Acacia ant plants house mutualistic ants as a defense mechanism and
      provide them with extrafloral nectar (EFN). Ant/plant mutualisms are widespread,
      but little is known about the biochemical basis of their species specificity.
      Despite its importance in these and other plant/animal interactions, little
      attention has been paid to the control of the chemical composition of nectar. We
      found high invertase (sucrose-cleaving) activity in Acacia EFN, which thus
      contained no sucrose. Sucrose, a disaccharide common in other EFNs, usually
      attracts nonsymbiotic ants. The EFN of the ant acacias was therefore unattractive
      to such ants. The Pseudomyrmex ants that are specialized to live on Acacia had
      almost no invertase activity in their digestive tracts and preferred sucrose-free
      EFN. Our results demonstrate postsecretory regulation of the carbohydrate
      composition of nectar.

PMID- 15845853
TI  - Comparative metagenomics of microbial communities.
AB  - The species complexity of microbial communities and challenges in culturing
      representative isolates make it difficult to obtain assembled genomes. Here we
      characterize and compare the metabolic capabilities of terrestrial and marine
      microbial communities using largely unassembled sequence data obtained by shotgun
      sequencing DNA isolated from the various environments. Quantitative gene content
      analysis reveals habitat-specific fingerprints that reflect known characteristics
      of the sampled environments. The identification of environment-specific genes
      through a gene-centric comparative analysis presents new opportunities for
      interpreting and diagnosing environments.

PMID- 15845856
TI  - Brain uptake kinetics of nicotine and cotinine after chronic nicotine exposure.
AB  - Blood-brain barrier (BBB) nicotine transfer has been well documented in view of
      the fact that this alkaloid is a cerebral blood flow marker. However, limited
      data are available that describe BBB penetration of the major tobacco alkaloids
      after chronic nicotine exposure. This question needs to be addressed, given long
      term nicotine exposure alters both BBB function and morphology. In contrast to
      nicotine, it has been reported that cotinine (the major nicotine metabolite) does
      not penetrate the BBB, yet cotinine brain distribution has been well documented
      after nicotine exposure. Surprisingly, therefore, the literature indirectly
      suggests that central nervous system cotinine distribution occurs secondarily to
      nicotine brain metabolism. The aims of the current report are to define BBB
      transfer of nicotine and cotinine in naive and nicotine-exposed animals. Using an
      in situ brain perfusion model, we assessed the BBB uptake of [3H]nicotine and
      [3H]cotinine in naive animals and in animals exposed chronically to S-(-)nicotine
      (4.5 mg/kg/day) through osmotic minipump infusion. Our data demonstrate that 1)
      [3H]nicotine BBB uptake is not altered in the in situ perfusion model after
      chronic nicotine exposure, 2) [3H]cotinine penetrates the BBB, and 3) similar to
      [3H]nicotine, [3H]cotinine BBB transfer is not altered by chronic nicotine
      exposure. To our knowledge, this is the first report detailing the uptake of
      nicotine and cotinine after chronic nicotine exposure and quantifying the rate of
      BBB penetration by cotinine.

PMID- 15845857
TI  - Neurochemical and behavioral responses to cocaine in adult male rats with
      neonatal isolation experience.
AB  - Our research demonstrates that neonatal isolation (ISO; 1 h/day isolation;
      postnatal days 2-9) enhances extracellular, ventral striatal dopamine (DA)
      responses to psychostimulants in infant and juvenile rats. In adult rats, we find
      ISO facilitates acquisition and maintenance of cocaine self-administration. We
      now test whether ISO enhances cocaine-induced accumbens DA levels in adults using
      in vivo microdialysis. Behavioral responses to cocaine and DA antagonists were
      also examined. Adult male rats were derived from litters subjected to ISO or
      nonhandled (NH) control conditions. In experiment 1, microdialysis probes were
      aimed at accumbens core and separate groups administered vehicle or cocaine (5
      and 10 mg/kg i.p.). Samples were analyzed for DA levels via high-performance
      liquid chromatography. In experiment 2, ISO and NH rats were administered one of
      these cocaine doses, and locomotor activity was assessed. Effects of cocaine (0.3
      30 mg/kg), the D(1) antagonist SCH23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1
      phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (0.003-0.03 mg/kg)], and the D(2)
      antagonist eticlopride (0.01-0.1 mg/kg) on disruption of responding for food were
      examined in experiment 3. Cocaine plasma levels were assessed in experiment 4.
      ISO enhanced cocaine-induced increases in accumbens DA levels. Furthermore, the
      D(2), but not D(1), antagonist disrupted behavior to a greater extent in ISO
      versus NH rats. Yet, ISO did not significantly alter behavioral responses to
      cocaine or cocaine plasma levels. These data show that the ability of ISO to
      enhance accumbens DA responses to cocaine endures into adulthood. Moreover, that
      ISO rats are more sensitive to a D(2) antagonist may reflect decreased levels of
      this receptor type as we showed previously in infant rats.

PMID- 15845858
TI  - Variability of CYP3A7 expression in human fetal liver.
AB  - Fetal liver CYP3A7 plays an important role in placental estriol synthesis during
      pregnancy, yet little is known concerning the extent or consequences of
      variability in expression. The purpose of this investigation was to characterize
      the variability in CYP3A7 expression using several phenotypic measures in a panel
      of 54 fetal livers ranging in age from 76 days to 32 weeks gestation. CYP3A7 mRNA
      expression was measured using quantitative polymerase chain reaction, whereas
      immunoreactive CYP3A7 was determined using an affinity-purified antipeptide
      antibody. Variability in catalytic activity was evaluated using testosterone and
      dehydroepiandrosterone (DHEA) as substrates. Across the entire panel, CYP3A7 was
      the most abundant CYP3A mRNA species present and varied 634-fold from 151 to
      95,700 transcripts/ng total RNA, corrected for 18S ribosomal RNA. CYP3A4
      expression was minimal based on mRNA expression (1000-fold lower than CYP3A7) and
      the ratio of testosterone 2alpha- (T2alphaH) to 6beta- (T6betaH) hydroxylation.
      T2alphaH and T6betaH were highly correlated (r(2) = 0.859), and the correlation
      increased (r(2) = 0.974) in livers with CYP3A5*3/*3 genotypes implying that the
      same enzyme (CYP3A7) generated both products. Overall, T2alphaH and DHEA16alphaH
      activities varied 175- and 250-fold, respectively. A subset of five samples had
      extremely low mRNA, protein, and catalytic activity, possibly due to pathology
      affecting fetal viability (anencephaly, porencephaly). In the remaining samples,
      T2alphaH activity varied 6.7-fold (358 +/- 142, range 97 to 643 pmol/min/mg) and
      DHEA16alphaH activity varied 6.2-fold (8.07 +/- 2.87, range 2.41 to 14.9
      nmol/min/mg). Observed variability in CYP3A7 activity was not related to
      CYP3A7*2, and alternative regulatory mechanisms require further investigation.

PMID- 15845859
TI  - Systemic morphine inhibits dorsal horn projection neurons through spinal
      cholinergic system independent of descending pathways.
AB  - Cholinergic circuitry and muscarinic receptors within the spinal cord have been
      proposed to contribute to the analgesic effects of systemic morphine. In this
      study, we determined whether the descending pathways are involved in the
      inhibitory effect of systemic morphine on dorsal horn projection neurons mediated
      by activation of the spinal cholinergic system. Single-unit activity of dorsal
      horn projection neurons was recorded in anesthetized rats. The neuronal responses
      to mechanical stimuli applied to the receptive field were determined before and
      after intravenous injection of morphine. The inhibitory effect of intravenous
      morphine on dorsal horn neurons was also tested before and after topical spinal
      application of the muscarinic antagonist atropine in both intact and spinally
      transected rats. Intravenous injection of 2.5 mg/kg morphine significantly
      inhibited the evoked response of dorsal horn neurons in both intact and spinally
      transected rats. Spinal topical application of the mu opioid antagonist H-d-Phe
      Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) completely blocked the effect of
      morphine on dorsal horn neurons. In addition, spinal application of 10 microM
      atropine significantly attenuated the effect of systemic morphine. In rats
      subjected to cervical spinal transection, atropine produced a similar attenuation
      of the inhibitory effect of systemic morphine on dorsal horn neurons. Data from
      this electrophysiological study suggest that systemic morphine inhibits ascending
      dorsal horn neurons through stimulation of spinal mu opioid receptors.
      Furthermore, activation of the local spinal cholinergic circuitry and muscarinic
      receptors is involved in the inhibitory effect of systemic morphine on dorsal
      horn projection neurons independent of descending pathways.

PMID- 15845860
TI  - Consequences of abrupt glutathione depletion in murine Clara cells:
      ultrastructural and biochemical investigations into the role of glutathione loss
      in naphthalene cytotoxicity.
AB  - Glutathione plays many critical roles within the cell, including offering
      protection from reactive chemicals. The bioactivated toxicant naphthalene forms
      chemically reactive intermediates that can deplete glutathione and covalently
      bind to cellular proteins. Naphthalene selectively injures the nonciliated
      epithelial cells of the intrapulmonary airways (i.e., Clara cells). This study
      attempted to define what role glutathione loss plays in naphthalene cytotoxicity
      by comparing Swiss-Webster mice treated with naphthalene with those treated with
      the glutathione depletor diethylmaleate. High-resolution imaging techniques were
      used to evaluate acute changes in Clara cell ultrastructure, membrane
      permeability, and cytoskeleton structure. A single dose of either diethylmaleate
      (1000 mg/kg) or naphthalene (200 mg/kg) caused similar glutathione losses in
      intrapulmonary airways (< 20% of control). Diethylmaleate did not increase
      membrane permeability, disrupt mitochondria, or lead to cell death--hallmark
      features of naphthalene cytotoxicity. However, diethylmaleate treatment did cause
      Clara cell swelling, plasma membrane blebs, and actin cytoskeleton disruptions
      similar to naphthalene treatment. Structural changes in mitochondria and Golgi
      bodies also were noted. Changes in ATP levels were measured as an indication of
      overall cell function, in isolated airway explants incubated with diethylmaleate,
      naphthalene, or naphthalene metabolites in vitro. Only the reactive metabolites
      of naphthalene caused significant ATP losses. Unlike the lethal injury caused by
      naphthalene, the disruptive cellular changes associated with glutathione loss
      from diethylmaleate seemed to be reversible after recovery of glutathione levels.
      This suggests that glutathione depletion may be responsible for some aspects of
      naphthalene cytotoxicity, but it is not sufficient to cause cell death without
      further stresses.

PMID- 15845861
TI  - Comparative pharmacophore modeling of organic anion transporting polypeptides: a
      meta-analysis of rat Oatp1a1 and human OATP1B1.
AB  - The organic anion transporting polypeptides OATPs are key membrane transporters
      for which crystal structures are not currently available. They transport a
      diverse array of xenobiotics and are expressed at the interface of hepatocytes,
      renal tubular cells, enterocytes, and the choroid plexus. To aid the
      understanding of the key molecular features for substrate-transporter
      interactions, pharmacophore models were produced for the two OATPs that have been
      most extensively studied, namely rat Oatp1a1 and human OATP1B1. Literature data
      from Chinese hamster ovary, HeLa, human embryonic kidney 293 cells, and Xenopus
      laevis oocytes were used to construct pharmacophores for each individual
      transporter which were later merged to show similarities across cell lines for
      the same transporter. Additionally, meta-pharmacophores were generated from the
      combined datasets of each cell system used with the same transporter. The
      pharmacophores for each transporter consisted of hydrogen bond acceptor and
      hydrophobic features. There was good agreement between the merged and meta
      pharmacophores containing two hydrogen bond acceptors and two or three
      hydrophobic features for Oatp1a1 and OATP1B1. External test sets were used to
      validate the individual pharmacophores. The meta-pharmacophores were also used to
      make predictions for molecules not included in the models and provided new
      molecular insight into the key features for these OATP transporters. This
      approach can be extended to other transporters for which limited data are
      available.

PMID- 15845862
TI  - Interleukin-10-secreting "regulatory" T cells induced by glucocorticoids and
      beta2-agonists.
AB  - Greater clinical benefit in controlling the symptoms of asthma is frequently
      observed through combining moderate doses of inhaled glucocorticoids together
      with long-acting beta(2)-agonists, as compared with increasing glucocorticoid
      dosage alone. To address in vitro whether glucocorticoids plus beta(2)-agonists,
      compared with glucocorticoids alone, have greater inhibitory activity on CD4+ T
      cell responses to allergen, peripheral blood CD4+ T cell responses to allergen
      were compared in the presence or absence of the glucocorticoid fluticasone
      proprionate and the short- and long-acting beta(2)-agonists salbutamol and
      salmeterol, respectively. Fluticasone proprionate inhibited interleukin (IL)-5
      and IL-13 and enhanced IL-10 synthesis in allergen-stimulated cultures in a
      concentration-dependent manner. Salmeterol, but not salbutamol, inhibited IL-5
      and IL-13 and enhanced IL-10 synthesis in these cultures. When used in
      combination the two drugs demonstrated an additive effect on this pattern of
      cytokine production. Allergen-specific T cell lines induced in the presence of
      salmeterol and fluticasone proprionate inhibited IL-5 and IL-13 production by
      allergen-specific Th2 cell lines in an IL-10-dependent manner. Thus fluticasone
      proprionate and salmeterol increased IL-10 and reduced Th2 cytokine synthesis
      additively in allergen stimulated human CD4+ T cells.

PMID- 15845863
TI  - In vivo effects of ozone exposure on protein adduct formation by 1
      nitronaphthalene in rat lung.
AB  - The incidence of serious photochemical smog events is steadily growing in urban
      environments around the world. The electrophilic metabolites of 1
      nitronaphthalene (1-NN), a common air pollutant in urban areas, have been shown
      to bind covalently to proteins. 1-NN specifically targets the airway epithelium,
      and the toxicity is synergized by prior long-term ozone exposure in rat. In this
      study we investigated the formation of 1-NN protein adducts in the rat airway
      epithelium in vivo and examined how prior long-term ozone exposure affects adduct
      formation. Eight adducted proteins, several involved in cellular antioxidant
      defense, were identified. The extent of adduction of each protein was calculated,
      and two proteins, peroxiredoxin 6 and biliverdin reductase, were adducted at high
      specific activities (0.36-0.70 and 1.0 nmol adduct/nmol protein). Furthermore,
      the N-terminal region of calreticulin, known as vasostatin, was adducted only in
      ozone-exposed animals. Although vasostatin was adducted at relatively low
      specific activity (0.01 nmol adduct/nmol protein), the adduction only in ozone
      exposed animals makes it a candidate protein for elucidating the synergistic
      toxicity between ozone and 1-NN. These studies identified in vivo protein targets
      for reactive 1-NN metabolites that are potentially associated with the mechanism
      of 1-NN toxicity and the synergistic effects of ozone.

PMID- 15845864
TI  - Interleukin-17 induces hyperresponsive interleukin-8 and interleukin-6 production
      to tumor necrosis factor-alpha in structural lung cells.
AB  - Lung epithelial cells contribute to local inflammation by the production of pro
      inflammatory mediators like interleukin (IL)-8 and IL-6. Although their
      production depends on gene transcription, previous studies showed that post
      transcriptional mechanisms modulate IL-8 and IL-6 production. Human lung
      epithelial cells turn from normoresponsive into hyperresponsive IL-8- and IL-6
      producing cells when their IL-8 and IL-6 mRNA degradation is reduced. We
      hypothesized that IL-17, a mediator predominantly released by memory T cells and
      present in airways of individuals with asthma, would modulate rather than induce
      IL-8 and IL-6 production by both human lung epithelial cells and fibroblasts. We
      show here for both cell types that IL-17 was a weak stimulus of IL-8 and IL-6
      production, but markedly enhanced IL-8 and IL-6 responses to another stimulus,
      such as tumor necrosis factor-alpha. This modulatory effect of IL-17 was
      paralleled by a reduced IL-8 and IL-6 mRNA degradation, with no effect on IL-8
      and IL-6 gene transcription. In conclusion, IL-17 particularly affects post
      transcriptional regulation of IL-8 and IL-6 expression leading to enhanced IL-8
      and IL-6 responses to secondary stimuli, and is only a weak proinflammatory
      stimulus by itself. This poses the interesting concept that by releasing IL-17
      from memory T cells, the adaptive immune system instructs lung structural cells
      as part of the innate immune system to respond more vigorously.

PMID- 15845865
TI  - Airway hyperresponsiveness in the absence of CD4+ T cells after primary but not
      secondary challenge.
AB  - CD4+ T cells have been shown to play a role in the development of airway
      hyperresponsivness (AHR) and airway eosinophilia in mice using ablation as well
      as adoptive transfer experiments. However, as other T cell subsets (CD8, NKT) may
      play a role in these models, we examined the responses of sensitized CD4
      deficient mice after either primary or secondary airway allergen challenge. After
      sensitization, CD4-deficiency in mice was not associated with airway
      eosinophilia, allergen-specific IgE, or elevated levels of interleukin (IL)-4 or
      IL-13. Increases in lung CD8 T cells and IL-5 were observed and shown to be
      essential for AHR as demonstrated after CD8 T cell depletion or anti-IL-5
      treatment. In contrast to the response of sensitized CD4-deficient mice to
      primary allergen challenge, they failed to develop AHR after secondary allergen
      challenge. Although the importance of this CD4+ T cell-independent pathway in
      normal mice is unclear at this time, these studies identify the diversity of the
      cellular pathway, which may contribute to the development of AHR after primary
      allergen exposure of sensitized mice.

PMID- 15845866
TI  - Identification and analysis of axonemal dynein light chain 1 in primary ciliary
      dyskinesia patients.
AB  - Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder
      characterized by chronic infections of the upper and lower airways, randomization
      of left/right body asymmetry, and reduced fertility. The phenotype results from
      dysfunction of motile cilia of the respiratory epithelium, at the embryonic node
      and of sperm flagella. Ultrastructural defects often involve outer dynein arms
      (ODAs), that are composed of several light (LCs), intermediate, and heavy (HCs)
      dynein chains. We recently showed that recessive mutations of DNAH5, the human
      ortholog of the biflagellate Chlamydomonas ODA gamma-HC, cause PCD. In
      Chlamydomonas, motor protein activity of the gamma-ODA-HC is regulated by binding
      of the axonemal LC1. We report the identification of the human (DNAL1) and murine
      (Dnal1) orthologs of the Chlamydomonas LC1-gene. Northern blot and in situ
      hybridization analyses revealed specific expression in testis, embryonic node,
      respiratory epithelium, and ependyma, resembling the DNAH5 expression pattern. In
      silico protein analysis showed complete conservation of the LC1/gamma-HC binding
      motif in DNAL1. Protein interaction studies demonstrated binding of DNAL1 and
      DNAH5. Based on these findings, we considered DNAL1 a candidate for PCD and
      sequenced all exons of DNAL1 in 86 patients. Mutational analysis was negative,
      excluding a major role of DNAL1 in the pathogenesis of PCD.

PMID- 15845867
TI  - Cigarette smoke extract induces DNA damage but not apoptosis in human bronchial
      epithelial cells.
AB  - Whether DNA damage caused by cigarette smoke leads to repair or apoptosis has not
      been fully elucidated. The current study demonstrates that cigarette smoke
      induces single-strand DNA damage in human bronchial epithelial cells. Cigarette
      smoke also stimulated caspase 3 precursors as well as intact poly (ADP-ribose)
      polymerase (PARP) production, but did not activate caspase 3 or cleave PARP,
      while the alkaloid camptothecin did so. Neither apoptosis nor necrosis was
      induced by cigarette smoke when the insult was removed within a designated time
      period. In contrast, DNA damage following cigarette smoke exposure was repaired
      as evidenced by decreasing terminal dUTP-biotin nick-end labeling positivity. The
      PARP inhibitor, 3-aminobenzamide blocked this repair. Furthermore, cells
      subjected to DNA damage were able to survive and proliferate clonogenically when
      changed to smoke-free conditions. These results suggest that cigarette smoke
      induced DNA damage in bronchial epithelial cells is not necessarily lethal, and
      that PARP functions in the repair process. Our data also suggest that the potency
      of cigarettes as a carcinogen may result from their ability to induce DNA damage
      while failing to trigger the apoptotic progression permitting survival of cells
      harboring potentially oncogenic mutations.

PMID- 15845868
TI  - Effect of chronic ethanol administration on hepatic eNOS activity and its
      association with caveolin-1 and calmodulin in female rats.
AB  - Although chronic and excessive alcohol consumption is associated with liver
      disease, the mechanism of alcoholic liver injury is still not clear. Whether
      reduced hepatic production of nitric oxide, which is evident in models of liver
      injury, is associated with alcohol-induced liver injury has not been
      investigated. We measured nitric oxide synthase (NOS) activity in the liver of
      pair-fed rats receiving liquid diet with or without alcohol [3% (vol/vol)] for 12
      wk. Compared with control rats, hepatic NOS activity was significantly reduced in
      alcohol-treated rats along with the evidence of liver injury. Interestingly,
      there was no difference in the hepatic expression of endothelial NOS (eNOS)
      between ethanol-fed and pair-fed rats. We then tested the hypothesis that an
      imbalance between the binding of eNOS with inhibitory and stimulatory proteins
      may underlie the reduced activity of eNOS because eNOS catalytic activity is
      regulated partly through dynamic interactions with the inhibitory protein
      caveolin-1 and the stimulatory protein calmodulin. We found that hepatic caveolin
      1 was markedly increased in alcohol-treated rats compared with control rats,
      whereas calmodulin remained unaltered. The binding of caveolin-1 and calmodulin
      with eNOS was increased and decreased, respectively, in alcohol-treated rats. Our
      results suggest that chronic alcohol intake attenuates hepatic eNOS activity by
      increasing the expression of the inhibitory protein caveolin-1 and enhancing its
      binding with eNOS.

PMID- 15845869
TI  - Grp78, Grp94, and Grp170 interact with alpha1-antitrypsin mutants that are
      retained in the endoplasmic reticulum.
AB  - In alpha1-antitrypsin (alpha1-AT) deficiency, a mutant form of alpha1-AT
      polymerizes in the endoplasmic reticulum (ER) of liver cells resulting in chronic
      hepatitis and hepatocellular carcinoma by a gain of toxic function mechanism.
      Although some aspects of the cellular response to mutant alpha1-AT Z have been
      partially characterized, including the involvement of several proteasomal and
      nonproteasomal mechanisms for disposal, other parts of the cellular response
      pathways, particularly the chaperones with which it interacts and the signal
      transduction pathways that are activated, are still not completely elucidated.
      The alpha1-AT Z molecule is known to interact with calnexin, but, according to
      one study, it does not interact with Grp78. To carry out a systematic search for
      the chaperones with which alpha1-AT Z interacts in the ER, we used chemical cross
      linking of several different genetically engineered cell systems. Mutant alpha1
      AT Z was cross-linked with Grp78, Grp94, calnexin, Grp170, UDP-glucose
      glycoprotein:glucosyltransferase, and two unknown proteins of approximately 110
      130 kDa. Sequential immunoprecipitation/immunoblot analysis and
      coimmunoprecipitation techniques demonstrated each of these interactions without
      chemical cross-linking. The same chaperones were found to interact with two
      nonpolymerogenic alpha1-AT mutants that are retained in the ER, indicating that
      these interactions are not specific for the alpha1-AT Z mutant. Moreover, sucrose
      density gradient centrifugation studies suggest that approximately 85% of alpha1
      AT Z exists in heterogeneous soluble complexes with multiple chaperones and
      approximately 15% in extremely large polymers/aggregates devoid of chaperones.
      Agents that perturb the synthesis and/or activity of ER chaperones such as
      tunicamycin and calcium ionophore A23187, have different effects on the
      solubility and degradation of alpha1-AT Z as well as on its residual secretion.

PMID- 15845870
TI  - Altered hepatic cholesterol metabolism compensates for disruption of
      phosphatidylcholine transfer protein in mice.
AB  - Phosphatidylcholine transfer protein (PC-TP) is a member of the steroidogenic
      acute regulatory transfer protein-related domain superfamily and is enriched in
      liver. To explore a role for PC-TP in hepatic cholesterol metabolism, Pctp-/- and
      wild-type C57BL/6J mice were fed a standard chow diet or a high-fat, high
      cholesterol lithogenic diet. In chow-fed Pctp-/- mice, acyl CoA:cholesterol
      acyltransferase (Acat) activity was markedly increased, 3-hydroxy-3
      methylglutaryl-CoA reductase activity was unchanged, and cholesterol 7alpha
      hydroxylase activity was reduced. Consistent with increased Acat activity,
      esterified cholesterol concentrations in livers of Pctp-/- mice were increased,
      whereas unesterified cholesterol concentrations were reduced. Hepatic
      phospholipid concentrations were also decreased in the absence of PC-TP and
      consequently, unesterified cholesterol-to-phospholipid ratios in liver remained
      unchanged. The lithogenic diet downregulated 3-hydroxy-3-methylglutaryl-CoA
      reductase in wild-type and Pctp-/- mice, whereas Acat was increased only in wild
      type mice. In response to the lithogenic diet, a greater reduction in cholesterol
      7alpha-hydroxylase activity in Pctp-/- mice could be attributed to increased size
      and hydrophobicity of the bile salt pool. Despite higher hepatic phospholipid
      concentrations, the unesterified cholesterol-to-phospholipid ratio increased. The
      lack of Acat upregulation suggests that, in the setting of the dietary challenge,
      the capacity for esterification to defend against hepatic accumulation of
      unesterified cholesterol was exceeded in the absence of PC-TP expression. We
      speculate that regulation of cholesterol homeostasis is a physiological function
      of PC-TP in liver, which can be overcome with a cholesterol-rich lithogenic diet.

PMID- 15845871
TI  - Lipopolysaccharide-induced liver injury in rats treated with the CYP2E1 inducer
      pyrazole.
AB  - Elevated LPS and elevated cytochrome P-450 2E1 (CYP2E1) in liver are two major
      independent risk factors in alcoholic liver disease. We investigated possible
      synergistic effects of the two risk factors in causing oxidative stress and liver
      injury. Sprague-Dawley rats were injected intraperitoneally with pyrazole
      (inducer of CYP2E1) for 2 days, and then LPS was injected via tail vein. Other
      rats were treated with pyrazole alone or LPS alone or saline. Eight hours later,
      blood was collected and livers were excised. Pathological evaluation showed
      severe inflammatory responses and necroses only in liver sections from rats in
      the pyrazole plus LPS group; blood transaminase levels were significantly
      elevated only in the combination group. Activities of caspase-3 and -9 and
      positive terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate
      nick-end labeling staining were highest in the LPS alone and the LPS plus
      pyrazole group, with no significant difference between the two groups. Lipid
      peroxidation and protein carbonyls in liver homogenate as well as in situ
      superoxide production were maximally elevated in the LPS plus pyrazole group.
      Levels of nitrite plus nitrate and inducible nitric oxide (NO) synthase (iNOS)
      content were comparably elevated in LPS alone and the LPS plus pyrazole group;
      however, 3-nitrotyrosine adducts were elevated in the combined group but not the
      LPS group. It is likely that LPS induction of iNOS, which produces NO, coupled to
      pyrazole induction of CYP2E1 which produces superoxide, sets up conditions for
      maximal peroxynitrite formation and production of 3-nitrotyrosine adducts. CYP2E1
      activity and content were elevated in the pyrazole and the LPS plus pyrazole
      groups. Immunohistochemical staining indicated that distribution of CYP2E1 was in
      agreement with that of necrosis and production of superoxide. These results show
      that pyrazole treatment enhanced LPS-induced necrosis, not apoptosis. The
      enhanced liver necrosis appears to involve an increase in oxidative and
      nitrosative stress generated by the combination of LPS plus elevated CYP2E1
      levels.

PMID- 15845872
TI  - Glycine-extended gastrin stimulates cell proliferation and migration through a
      Rho- and ROCK-dependent pathway, not a Rac/Cdc42-dependent pathway.
AB  - Both amidated gastrin (Gamide) and glycine-extended gastrin (Ggly) stimulate
      gastrointestinal cell proliferation and migration. Binding of Gamide to the
      cholecystokinin-2 receptor activates small GTP-binding proteins of the Rho family
      (Rho, Rac, and Cdc42), and dominant-negative mutants of Rho or Cdc42 block Gamide
      stimulated cell proliferation and survival. In comparison, little is known about
      the Ggly signaling transduction pathway leading to cell proliferation and
      migration. The present study examined the roles of the small G proteins Rho, Rac,
      and Cdc42 in Ggly-induced proliferation and migration of the mouse gastric
      epithelial cell line IMGE-5. Ggly stimulated the activation of Rho and its
      downstream effector protein ROCK. The activation of Rho and ROCK mediated Ggly
      induced cell proliferation and migration as inhibition of Rho by C3, or ROCK by Y
      27632, completely blocked these effects of Ggly. Ggly also stimulated tyrosine
      phosphorylation of focal adhesion kinase, and stimulation was reversed by
      addition of C3 and Y-27632. In contrast to the effects of Rho and ROCK,
      inhibition of the Rac or Cdc42 pathways by expression of dominant-negative
      mutants of Rac or Cdc42 did not affect Ggly-induced cell proliferation and
      migration. These results demonstrate that Ggly stimulates IMGE-5 cell
      proliferation and migration through a Rho/ROCK-dependent pathway but not via Rac-
      or Cdc42-dependent pathways.

PMID- 15845873
TI  - Distinct roles of nitric oxide synthases and interstitial cells of Cajal in
      rectoanal relaxation.
AB  - Nitric oxide (NO) relaxes the internal anal sphincter (IAS), but its enzymatic
      source(s) remains unknown; neuronal (nNOS) and endothelial (eNOS) NO synthase
      (NOS) isoforms could be involved. Also, interstitial cells of Cajal (ICC) may be
      involved in IAS relaxation. We studied the relative roles of nNOS, eNOS, and c
      Kit-expressing ICC for IAS relaxation using genetic murine models. The basal IAS
      tone and the rectoanal inhibitory reflex (RAIR) were assessed in vivo by a
      purpose-built solid-state manometric probe and by using wild-type, nNOS-deficient
      (nNOS-/-), eNOS-deficient (eNOS-/-), and W/W(v) mice (lacking certain c-Kit
      expressing ICC) with or without L-arginine or N(omega)-nitro-L-arginine methyl
      ester (L-NAME) treatment. Moreover, the basal tone and response to electrical
      field stimulation (EFS) were studied in organ bath using wild-type and mutant
      IAS. In vivo, the basal tone of eNOS-/- was higher and W/W(v) was lower than wild
      type and nNOS-/- mice. L-arginine administered rectally, but not intravenously,
      decreased the basal tone in wild-type, nNOS-/-, and W/W(v) mice. However, neither
      L-arginine nor L-NAME affected basal tone in eNOS-/- mice. In vitro, L-arginine
      decreased basal tone in wild-type and nNOS-/- IAS but not in eNOS-/- or wild-type
      IAS without mucosa. The in vivo RAIR was intact in wild-type, eNOS-/-, and W/W(v)
      mice but absent in all nNOS-/- mice. EFS-induced IAS relaxation was also reduced
      in nNOS-/- IAS. Thus the basal IAS tone is largely controlled by eNOS in the
      mucosa, whereas the RAIR is controlled by nNOS. c-Kit-expressing ICC may not be
      essential for the RAIR.

PMID- 15845874
TI  - Cladosporium Avr2 inhibits tomato Rcr3 protease required for Cf-2-dependent
      disease resistance.
AB  - How plants recognize pathogens and activate defense is still mysterious. Direct
      interaction between pathogen avirulence (Avr) proteins and plant disease
      resistance proteins is the exception rather than the rule. During infection,
      Cladosporium fulvum secretes Avr2 protein into the apoplast of tomato leaves and,
      in the presence of the extracellular leucine-rich repeat receptor-like Cf-2
      protein, triggers a hypersensitive response (HR) that also requires the
      extracellular tomato cysteine protease Rcr3. We show here that Avr2 binds and
      inhibits Rcr3 and propose that the Rcr3-Avr2 complex enables the Cf-2 protein to
      activate an HR.

PMID- 15845875
TI  - Scaling in the time domain: universal dynamics of order fluctuations in Fe3Al.
AB  - By focusing a highly brilliant synchrotron x-ray beam to a micrometer spot on a
      sample, we measured in real time the x-ray intensity fluctuations associated with
      order fluctuations in crystalline materials. We applied this method to the binary
      alloy Fe3Al near its continuous A2-B2 phase transformation and determined a
      specific four-point time correlation function for the order parameter. From a
      detailed theoretical analysis, dynamical scaling in the time domain with a
      transition from noncritical to critical dynamics is disclosed.

PMID- 15845876
TI  - Bottom-up ecosystem trophic dynamics determine fish production in the Northeast
      Pacific.
AB  - We addressed the question of bottom-up versus top-down control of marine
      ecosystem trophic interactions by using annual fish catch data and satellite
      derived (SeaWiFS) chlorophyll a measurements for the continental margin of
      western North America. Findings reveal a marked alongshore variation in retained
      primary production that is highly correlated with the alongshore variation in
      resident fish yield. The highest productivity occurs off the coasts of Washington
      and southern British Columbia. Zooplankton data for coastal British Columbia
      confirm strong bottom-up trophic linkages between phytoplankton, zooplankton, and
      resident fish, extending to regional areas as small as 10,000 square kilometers.

PMID- 15845878
TI  - Voluntary exercise protects against acute doxorubicin cardiotoxicity in the
      isolated perfused rat heart.
AB  - The clinical use of doxorubicin (DOX) is limited by a dose-dependent
      cardiotoxicity. The purpose of this study was to determine whether voluntary
      exercise training would confer protection against DOX cardiotoxicity in the
      isolated perfused rat heart. Female Sprague-Dawley rats were randomly assigned to
      standard holding cages or cages with running wheels for 8 wk. Twenty-four hours
      after the sedentary (SED) or voluntary exercise (VEX) running period, rats were
      anesthetized with pentobarbital sodium, and hearts were isolated and perfused
      with oxygenated Krebs-Henseleit (KH) buffer at a constant flow of 15 ml/min.
      After a 20-min stabilization period, hearts were paced at 300 beats per minute
      and perfused with KH buffer containing 10 microM DOX for 60 min. A set of control
      hearts from SED and VEX rats were perfused under identical conditions without DOX
      for the same period. DOX perfusion led to significant decreases in left
      ventricular developed pressure, +dP/dt, and -dP/dt, and significant increases in
      LV lipid peroxidation in sedentary rats compared with non-DOX controls (P <
      0.05). Prior voluntary exercise training attenuated these DOX-induced effects and
      was associated with a significant increase (78%, P < 0.05) in heat shock protein
      (HSP72), but not mitochondrial isoform of SOD (MnSOD) or CuZnSOD protein
      expression in the hearts of wheel-run animals. These data indicate that chronic
      physical activity may provide resistance against the cardiac dysfunction and
      oxidative damage associated with DOX exposure and provide novel evidence of HSP72
      induction in the heart after voluntary exercise.

PMID- 15845877
TI  - Obesity and metabolic syndrome in circadian Clock mutant mice.
AB  - The CLOCK transcription factor is a key component of the molecular circadian
      clock within pacemaker neurons of the hypothalamic suprachiasmatic nucleus. We
      found that homozygous Clock mutant mice have a greatly attenuated diurnal feeding
      rhythm, are hyperphagic and obese, and develop a metabolic syndrome of
      hyperleptinemia, hyperlipidemia, hepatic steatosis, hyperglycemia, and
      hypoinsulinemia. Expression of transcripts encoding selected hypothalamic
      peptides associated with energy balance was attenuated in the Clock mutant mice.
      These results suggest that the circadian clock gene network plays an important
      role in mammalian energy balance.

PMID- 15845879
TI  - Effect of water deprivation on cognitive-motor performance in healthy men and
      women.
AB  - Whether mental performance is affected by slowly progressive moderate dehydration
      induced by water deprivation has not been examined previously. Therefore,
      objective and subjective cognitive-motor function was examined in 16 volunteers
      (8 females, 8 males, mean age: 26 yr) twice, once after 24 h of water deprivation
      and once during normal water intake (randomized cross-over design; 7-day
      interval). Water deprivation resulted in a 2.6% decrease in body weight. Neither
      cognitive-motor function estimated by a paced auditory serial addition task, an
      adaptive 5-choice reaction time test, a manual tracking test, and a Stroop word
      color conflict test nor neurophysiological function assessed by auditory event
      related potentials P300 (oddball paradigm) differed (P > 0.1) between the water
      deprivation and the control study. However, subjective ratings of mental
      performance changed significantly toward increased tiredness (+1.0 points) and
      reduced alertness (-0.9 points on a 5-point scale; both: P < 0.05), and higher
      levels of perceived effort (+27 mm) and concentration (+28 mm on a 100-mm scale;
      both: P < 0.05) necessary for test accomplishment during dehydration. Several
      reaction time-based responses revealed significant interactions between gender
      and dehydration, with prolonged reaction time in women but shortened in men after
      water deprivation (Stroop word-color conflict test, reaction time in women: +26
      ms, in men: -36 ms, P < 0.01; paced auditory serial addition task, reaction time
      in women +58 ms, in men -31 ms, P = 0.05). In conclusion, cognitive-motor
      function is preserved during water deprivation in young humans up to a moderate
      dehydration level of 2.6% of body weight. Sexual dimorphism for reaction time
      based performance is present. Increased subjective task-related effort suggests
      that healthy volunteers exhibit cognitive compensating mechanisms for increased
      tiredness and reduced alertness during slowly progressive moderate dehydration.

PMID- 15845880
TI  - Negative feedback regulation of nerve-mediated contractions by KCa channels in
      mouse urinary bladder smooth muscle.
AB  - When the urinary bladder is full, activation of parasympathetic nerves causes
      release of neurotransmitters that induce forceful contraction of the detrusor
      muscle, leading to urine voiding. The roles of ion channels that regulate
      contractility of urinary bladder smooth muscle (UBSM) in response to activation
      of parasympathetic nerves are not well known. The present study was designed to
      characterize the role of large (BK)- and small-conductance (SK) Ca(2+)-activated
      K(+) (K(Ca)) channels in regulating UBSM contractility in response to
      physiological levels of nerve stimulation in UBSM strips from mice. Nerve-evoked
      contractions were induced by electric field stimulation (0.5-50 Hz) in isolated
      strips of UBSM. BK and SK channel inhibition substantially increased the
      amplitude of nerve-evoked contractions up to 2.45 +/- 0.12- and 2.99 +/- 0.25
      fold, respectively. When both SK and BK channels were inhibited, the combined
      response was additive. Inhibition of L-type voltage-dependent Ca(2+) channels
      (VDCCs) in UBSM inhibited nerve-evoked contractions by 92.3 +/- 2.0%. These
      results suggest that SK and BK channels are part of two distinct negative
      feedback pathways that limit UBSM contractility in response to nerve stimulation
      by modulating the activity of VDCCs. Dysfunctional regulation of UBSM
      contractility by alterations in BK/SK channel expression or function may underlie
      pathologies such as overactive bladder.

PMID- 15845881
TI  - Sugar and fat conditioned flavor preferences in C57BL/6J and 129 mice: oral and
      postoral interactions.
AB  - C57BL/6J (B6) mice consume more sugar and fat solutions than do 129 mice in 24-h
      preference tests. Previous studies have attributed this observation to strain
      differences in taste responsiveness to these nutrients. We tested the hypothesis
      that differences in postingestive responsiveness contribute to the strain
      differences. In experiment 1, B6 and 129 mice were trained to associate
      consumption of a flavored solution (CS+) with intragastric (IG) infusions of 16%
      sucrose and a different flavored solution (CS-) with IG water infusions (22
      h/day). They were then retrained with new flavors paired with IG infusions of
      5.6% soybean oil and water. Although both strains developed preferences for the
      nutrient-paired CS+ solutions, the B6 mice displayed significantly stronger
      preferences. The B6 mice consumed more CS+ during training, which may have
      contributed to their enhanced preference. In a second experiment, training
      intakes were equated by giving B6 and 129 mice "isosweet" CS solutions prepared
      with different amounts of sucrose and saccharin. The B6 and 129 mice consumed
      more of the sugar- or fat-paired CS+ than the water-paired CS- during training.
      The two strains also displayed equally strong preferences for the CS+ over CS- in
      choice tests, indicating that they had similar postingestive responsiveness to
      the sucrose and soybean oil. We propose that B6 mice consume more sugar and fat
      than 129 mice because their stronger orosensory response stimulates greater
      intake, which leads to greater stimulation of postingestive nutrient detectors
      and further enhancement of consumption.

PMID- 15845882
TI  - UT-B is expressed in bovine rumen: potential role in ruminal urea transport.
AB  - The UT-A (SLC14a2) and UT-B (SLC14a1) genes encode a family of specialized urea
      transporter proteins that regulate urea movement across plasma membranes. In this
      report, we describe the structure of the bovine UT-B (bUT-B) gene and
      characterize UT-B expression in bovine rumen. Northern analysis using a full
      length bUT-B probe detected a 3.7-kb UT-B signal in rumen. RT-PCR of bovine mRNA
      revealed the presence of two UT-B splice variants, bUT-B1 and bUT-B2, with bUT-B2
      the predominant variant in rumen. Immunoblotting studies of bovine rumen tissue,
      using an antibody targeted to the NH2-terminus of mouse UT-B, confirmed the
      presence of 43- to 54-kDa UT-B proteins. Immunolocalization studies showed that
      UT-B was mainly located on cell plasma membranes in epithelial layers of the
      bovine rumen. Ussing chamber measurements of ruminal transepithelial transport of
      (14)C-labeled urea indicated that urea flux was characteristically inhibited by
      phloretin. We conclude that bUT-B is expressed in the bovine rumen and may
      function to transport urea into the rumen as part of the ruminant urea nitrogen
      salvaging process.

PMID- 15845883
TI  - Cardiovascular dysfunction caused by cecal ligation and puncture is attenuated in
      CD8 knockout mice treated with anti-asialoGM1.
AB  - The present study was designed to assess hemodynamics and myocardial function at
      18 h after injury caused by cecal ligation and puncture (CLP) in CD8-knockout
      mice treated with anti-asialoGM1 (CD8KO/alphaAsGM1 mice). Arterial pressure was
      measured by carotid artery cannulation, and left ventricular pressure-volume
      measurements were obtained by use of a 1.4-Fr conductance catheter. Blood acid
      base balance and indexes of hepatic, renal, and pulmonary injury were also
      measured. CD8KO/alphaAsGM1 mice exhibited higher mean arterial pressure and
      increased systemic vascular resistance compared with wild-type mice. Cardiac
      output was significantly decreased in wild-type, but not CD8KO/alphaAsGM1, mice
      compared with sham controls. Myocardial function was better preserved in
      CD8KO/alphaAsGM1 mice as indicated by less impairment of left ventricular
      pressure development over time, time varying maximum elastance, end-systolic
      pressure-volume relationship, and preload recruitable stroke work. The impairment
      in myocardial function was associated with induction of proinflammatory cytokine
      mRNAs in the hearts of wild-type mice. The hemodynamic derangements in wild-type
      mice were coupled with significant metabolic acidosis and elevated serum
      creatinine levels. Overall, this study shows that cardiovascular collapse and
      shock characterized by hypotension, myocardial depression, low systemic vascular
      resistance, and metabolic acidosis occurs after CLP in wild-type mice but is
      attenuated in CD8KO/alphaAsGM1 mice. These observations likely explain, in part,
      the previously observed survival advantage of CD8KO/alphaAsGM1 mice following
      CLP.

PMID- 15845884
TI  - Plasma hyperosmolality augments peripheral vascular response to baroreceptor
      unloading during heat stress.
AB  - The aim of this study was to elucidate the interactive effect of central
      hypovolemia and plasma hyperosmolality on regulation of peripheral vascular
      response and AVP secretion during heat stress. Seven male subjects were infused
      with either isotonic (0.9%; NOSM) or hypertonic (3.0%; HOSM) NaCl solution and
      then heated by perfusing 42 degrees C (heat stress; HT) or 34.5 degrees C water
      (normothermia; NT) through water perfusion suits. Sixty minutes later, subjects
      were exposed to progressive lower body negative pressure (LBNP) to -40 mmHg.
      Plasma osmolality (P(osmol)) increased by approximately 11 mosmol/kgH(2)O in HOSM
      conditions. The increase in esophageal temperature before LBNP was much larger in
      HT-HOSM (0.90 +/- 0.09 degrees C) than in HT-NOSM (0.30 +/- 0.07 degrees C) (P <
      0.01) because of osmotic inhibition of thermoregulation. During LBNP, mean
      arterial pressure was well maintained, and changes in thoracic impedance and
      stroke volume were similar in all conditions. Forearm vascular conductance (FVC)
      before application of LBNP was higher in HT than in NT conditions (P < 0.001) and
      was not influenced by P(osmol) within the thermal conditions. The reduction in
      FVC at -40 mmHg in HT-HOSM (-9.99 +/- 0.96 units; 58.8 +/- 4.1%) was
      significantly larger than in HT-NOSM (-6.02 +/- 1.23 units; 44.7 +/- 8.1%) (P <
      0.05), whereas the FVC response was not different between NT-NOSM and NT-HOSM.
      Plasma AVP response to LBNP did not interact with P(osmol) in either NT or HT
      conditions. These data indicate that there apparently exists an interactive
      effect of P(osmol) and central hypovolemia on the peripheral vascular response
      during heat stress, or peripheral vasodilated conditions, but not in
      normothermia.

PMID- 15845885
TI  - Sympathetic alpha-adrenergic regulation of blood flow and volume in hamsters
      arousing from hibernation.
AB  - Mammals arousing from hibernation display pronounced regional heterothermy, where
      the thoracic and head regions warm faster than the abdominal and hindlimb
      regions. We used laser-Doppler flowmetry to measure peripheral hind foot blood
      flow during hibernation and arousal and gamma imaging of technetium-labeled
      albumin to measure whole blood volume distribution in hamsters arousing from
      hibernation. It was discovered that the hibernating hamster responds to physical
      but not to sound or hypercapnic stimulation with rapid, 73% reduction of hind
      foot blood flow. Hind foot blood flow vasoconstriction was maintained from the
      onset of arousal until late in arousal when rectal temperature was rapidly
      increased. alpha-Adrenergic blockade early in arousal increased hind foot blood
      flow by 700%, suggesting that vasoconstriction was mediated by activation of
      sympathetic tone. Gamma imaging revealed that, by the early phase of arousal from
      hibernation, the blood volume of the body below the liver is greatly reduced,
      whereas blood volumes of the thorax and head are much greater than corresponding
      volumes in anesthetized hamsters. As arousal progresses and cardiac activity
      increases and regional heterothermy develops, this regional blood volume
      distribution is largely maintained; however, blood volume slowly decreases in the
      thoracic region and slowly increases in the shoulder and head regions. The rapid
      increase in rectal temperature, characteristic of mid- to late- arousal phases,
      is probably mediated, in part, by reduction of adrenergic tone on abdominal and
      hindlimb vasculature. Warm blood then moves into the hind body, produces an
      increase in temperature, blood flow, and blood volume in the hind body and
      compensatory reductions of blood volume in the neck, head, and thoracic regions.

PMID- 15845886
TI  - Dysfunctional Smad signaling contributes to abnormal smooth muscle cell
      proliferation in familial pulmonary arterial hypertension.
AB  - Mutations in the bone morphogenetic protein type II receptor gene (BMPR2) are the
      major genetic cause of familial pulmonary arterial hypertension (FPAH). Although
      smooth muscle cell proliferation contributes to the vascular remodeling observed
      in PAH, the role of BMPs in this process and the impact of BMPR2 mutation remains
      unclear. Studies involving normal human pulmonary artery smooth muscle cells
      (PASMCs) suggest site-specific responses to BMPs. Thus, BMP-4 inhibited
      proliferation of PASMCs isolated from proximal pulmonary arteries, but stimulated
      proliferation of PASMCs from peripheral arteries, and conferred protection from
      apoptosis. These differences were not caused by differential activation of BMP
      signaling pathways because exogenous BMP-4 led to phosphorylation of Smad1,
      p38(MAPK), and ERK1/2 in both cell types. However, the proproliferative effect of
      BMP-4 on peripheral PASMCs was found to be p38MAPK/ERK-dependent. Conversely,
      overexpression of dominant-negative Smad1 converted the response to BMP-4 in
      proximal PASMCs from inhibitory to proliferative. Furthermore, we confirmed that
      proximal PASMCs harboring kinase domain mutations in BMPR2 are deficient in Smad
      signaling and are unresponsive to the growth suppressive effect of BMP-4.
      Moreover, we show that the pulmonary vasculature of patients with familial and
      idiopathic PAH are deficient in the activated form of Smad1. We conclude that
      defective Smad signaling and unopposed p38(MAPK)/ERK signaling, as a consequence
      of mutation in BMPR2, underlie the abnormal vascular cell proliferation observed
      in familial PAH.

PMID- 15845887
TI  - Proapoptotic effects of caspase-1/interleukin-converting enzyme dominate in
      myocardial ischemia.
AB  - Caspase-1/interleukin-converting enzyme (ICE) is a cysteine protease
      traditionally considered to have importance as an inflammatory mediator, but not
      as an apoptotic effector. Because of the dual functions of this caspase, the
      pathophysiological impact of its reported upregulation in hypertrophy and heart
      failure is not known. Here, the consequences of increased myocardial expression
      of procaspase-1 were examined on the normal and ischemically injured heart. In
      unstressed mouse hearts with a 30-fold increase in procaspase-1 content,
      unprocessed procaspase-1 was well tolerated, without detectable pathology.
      Cardiomyocyte processing and activation of caspase-1 and caspase-3 occurred after
      administration of endotoxin or with transient myocardial ischemia. In post
      ischemic hearts, procaspase-1 overexpression was associated with strikingly
      increased cardiac myocyte apoptosis in the peri- and noninfarct regions and with
      50% larger myocardial infarctions. Tissue culture studies revealed that
      procaspase-1 processing/activation is stimulated by hypoxia, and that caspase-1
      acts in synergy with hypoxia to stimulate caspase-3 mediated apoptosis without
      activating upstream caspases. These data demonstrate that the proapoptotic
      effects of caspase-1 can significantly impact the myocardial response to ischemia
      and suggest that conditions in which procaspase-1 in the heart is increased may
      predispose to apoptotic myocardial injury under conditions of physiological
      stress.

PMID- 15845888
TI  - NAD(P)H oxidases in rat basilar arterial endothelial cells.
AB  - BACKGROUND AND PURPOSE: Reactive oxygen species (ROS) may play a critical role in
      the regulation of vascular tone and development of vascular diseases, such as
      stroke. NAD(P)H oxidase is a major source of ROS in vascular cells, including
      endothelial cells. It has been considered that Nox2 and Nox4 are exclusively
      expressed among Nox homologues in the endothelial cells of noncerebral blood
      vessels. However, the precise molecular identity of the NAD(P)H oxidase in the
      endothelial cells of the cerebral arteries is not fully understood. We examined
      the expression of Nox homologues and their activation mechanism in the
      endothelial cells of the cerebral arteries. METHODS: We isolated and cultured
      basilar artery endothelial cells (BAECs) of Sprague-Dawley rats. Expression of
      NAD(P)H oxidase was examined by reverse-transcription-polymerase chain reaction
      (RT-PCR) and immunohistological staining. RESULTS: RT-PCR disclosed abundant
      expression of Nox4 with marginal Nox2 in BAEC. In addition, Nox1 was expressed
      highly both at mRNA and protein levels in BAECs. Immunohistological staining also
      showed the prominent expression of Nox1 in the endothelial cells of the basilar
      artery. With respect to the cytosolic components of NAD(P)H oxidases, BAECs
      expressed p67phox and, to a lesser extent, p47phox, Noxo1, and Noxa1. Both NADH
      and NADPH induced superoxide production of the BAEC membranes. The phagocyte-type
      cytosolic components, p47phox and p67phox, significantly enhanced the NADH
      induced superoxide production of the BAEC membranes, whereas the components
      failed to increase the NADPH-induced superoxide production. CONCLUSIONS: Nox1 is
      highly expressed in the endothelial cells of the cerebral arteries along with
      Nox2 and Nox4, and the endothelial NAD(P)H oxidase of the cerebral arteries may
      have a unique activation mechanism by the phagocyte-type cytosolic components.

PMID- 15845889
TI  - Chagasic cardiomyopathy is independently associated with ischemic stroke in
      Chagas disease.
AB  - BACKGROUND AND PURPOSE: Chagasic cardiomyopathy is independently associated with
      ischemic stroke in Chagas disease. American trypanosomiasis, Chagas disease (CD),
      is a major public health problem in South America. We sought to evaluate
      prevalence of vascular risk factors for stroke in patients with stroke caused by
      CD. METHODS: Ninety-four consecutive CD stroke patients and 150 consecutive
      nonchagasic stroke patients were studied. CD was confirmed when both
      immunofluorescence and hemagglutination serology were positive. Data collected
      included age, sex, vascular risk factors, diagnostic stroke subtype (TOAST
      classification), and echocardiography findings. Fasting plasma levels of protein
      C, protein S, antithrombin III, homocysteine, activated protein C resistance, IgG
      anticardiolipin antibodies, lupus anticoagulant, and genetic tests for the factor
      V Leiden and the C677T methylene tetrahydrofolate reductase gene mutation were
      determined. RESULTS: CD patients had a mean age of 56.31 years compared with
      61.59 years for non-CD stroke patients (P=0.0002). Cardioembolism occurred in
      56.38% of CD stroke patients compared with 9.33% in controls (P=0.000), whereas
      atherothrombotic strokes occurred in 8.51% of CD strokes versus 20% in controls
      (P=0.016), and small-vessel stroke in 9.57% of CD stroke patients versus 34.67%
      in controls (P=0.000). Apical aneurysm (37.23% versus 0.67%; OR, 88.39), left
      ventricular dilatation (23.4% versus 5.33%; OR, 5.42), mural thrombus (11.7
      versus 2%; OR, 6.49) and abnormal electrocardiography (ECG) (66% versus 23.33%;
      OR, 2.87) were significantly higher in the group of chagasic stroke patients. No
      statistical differences were observed in thrombophilia between both groups. The
      significant variables that predicted CD stroke patients on a stepwise logistical
      regression model were apical aneurysm, cardiac insufficiency, ECG arrhythmia,
      female gender, and hypertension. CONCLUSIONS: Chagasic cardiomyopathy is
      independently associated with ischemic stroke, whereas hypercoagulable states do
      not appear to be major contributors to the excess stroke risk seen in patients
      with CD.

PMID- 15845890
TI  - Cannabidiol prevents cerebral infarction via a serotonergic 5-hydroxytryptamine1A
      receptor-dependent mechanism.
AB  - BACKGROUND AND PURPOSE: Cannabidiol has been reported to be a neuroprotectant,
      but the neuroprotective mechanism of cannabidiol remains unclear. We studied the
      neuroprotective mechanism of cannabidiol in 4-hour middle cerebral artery (MCA)
      occlusion mice. METHODS: Male MCA occluded mice were treated with cannabidiol,
      abnormal cannabidiol, anandamide, methanandamide, cannabidiol plus capsazepine,
      and cannabidiol plus WAY100135 before and 3 hours after MCA occlusion. The
      infarct size was determined after 24 hours (2,3,5-triphenyltetrazolium chloride
      staining). Cerebral blood flow (CBF) was measured at, before and 1, 2, 3, and 4
      hours after MCA occlusion. RESULTS: Cannabidiol significantly reduced the infarct
      volume induced by MCA occlusion in a bell-shaped curve. Similarly, abnormal
      cannabidiol but not anandamide or methanandamide reduced the infarct volume.
      Moreover, the neuroprotective effect of cannabidiol was inhibited by WAY100135, a
      serotonin 5-hydroxytriptamine1A (5-HT1A) receptor antagonist but not capsazepine
      a vanilloid receptor antagonist. Cannabidiol increased CBF to the cortex, and the
      CBF was partly inhibited by WAY100135 in mice subjected to MCA occlusion.
      CONCLUSIONS: Cannabidiol and abnormal cannabidiol reduced the infarct volume.
      Furthermore, the neuroprotective effect of cannabidiol was inhibited by WAY100135
      but not capsazepine, and the CBF increased by cannabidiol was partially reversed
      by WAY100135. These results suggested that the neuroprotective effect of
      cannabidiol may be related to the increase in CBF through the serotonergic 5-HT1A
      receptor.

PMID- 15845891
TI  - Relation of parity with common carotid intima-media thickness among women of the
      Study of Health in Pomerania.
AB  - BACKGROUND AND PURPOSE: Metabolic and hormonal changes associated with pregnancy
      and childbirth are assumed to contribute to the development of cardiovascular
      disease among women. We analyzed the association of parity with common carotid
      intima-media thickness (IMT), which has a predictive value of subsequent
      myocardial infarction and stroke. METHODS: The Study of Health in Pomerania
      (SHIP), an epidemiological study of the general population in the northeast of
      Germany, included 1195 women aged 45 to 79 years. Mean and maximum far-wall IMT
      of the common carotid arteries were assessed by high-resolution ultrasound. All
      women were comprehensively characterized as to their reproductive history as well
      as to socioeconomic, behavioral, and biological risk factors. RESULTS: There was
      a U-shaped association between the number of children (from 0 to > or =4) and
      mean and maximum IMT. Nulliparous women had the highest age-adjusted mean (0.81
      mm [95% CI, 0.78 to 0.84]) and maximum IMT (1.04 mm [95% CI, 1.00 to 1.09]), and
      women with single parity the lowest (mean IMT, 0.73 [95% CI, 0.72 to 0.74];
      maximum IMT, 0.91 mm [95% CI, 0.89 to 0.93]; P<0.001 versus nulliparity for both
      parameters). Stepwise multivariate adjustment for socioeconomic factors,
      lifestyle variables, and biological variables attenuated the magnitude of this
      association yet significance remained. CONCLUSIONS: Nulliparity and higher number
      of children are associated with increased carotid IMT. These findings add support
      to the hypothesis of a link between the reproductive history of women and
      cardiovascular disease.

PMID- 15845892
TI  - Amnionless function is required for cubilin brush-border expression and intrinsic
      factor-cobalamin (vitamin B12) absorption in vivo.
AB  - Amnionless (AMN) and cubilin gene products appear to be essential functional
      subunits of an endocytic receptor called cubam. Mutation of either gene causes
      autosomal recessive Imerslund-Grasbeck syndrome (I-GS, OMIM no. 261100) in
      humans, a disorder characterized by selective intestinal malabsorption of
      cobalamin (vitamin B12) and urinary loss of several specific low-molecular-weight
      proteins. Vital insight into the molecular pathology of I-GS has been obtained
      from studies of dogs with a similar syndrome. In this work, we show that I-GS
      segregates in a large canine kindred due to an in-frame deletion of 33
      nucleotides in exon 10 of AMN. In a second, unrelated I-GS kindred, affected dogs
      exhibit a homozygous substitution in the AMN translation initiation codon.
      Studies in vivo demonstrated that both mutations abrogate AMN expression and
      block cubilin processing and targeting to the apical membrane. The essential
      features of AMN dysfunction observed in vivo are recapitulated in a heterologous
      cell-transfection system, thus validating the system for analysis of AMN-cubilin
      interactions. Characterization of canine AMN mutations that cause I-GS
      establishes the canine model as an ortholog of the human disorder well suited to
      studies of AMN function and coevolution with cubilin.

PMID- 15845893
TI  - Oligoclonal expansion of T lymphocytes with multiple second-site mutations leads
      to Omenn syndrome in a patient with RAG1-deficient severe combined
      immunodeficiency.
AB  - Omenn syndrome (OS) is a rare primary immunodeficiency characterized by the
      presence of activated/oligoclonal T cells, eosinophilia, and the absence of
      circulating B cells. OS patients carry leaky mutations of recombination
      activating genes (RAG1 or RAG2) resulting in partial V(D)J recombination
      activity, whereas null mutations cause severe combined immunodeficiency with
      absence of mature T and B cells (T-B- SCID). Here we describe somatic mosaicism
      due to multiple second-site mutations in a patient with RAG1 deficiency. We found
      that he is homozygous for a single base deletion in the RAG1 gene, which results
      in frameshift and likely abrogates the protein function. However, the patient
      showed typical OS features. Molecular analysis revealed that several second-site
      mutations, all of which restored the RAG1 reading frame and resulted in missense
      mutations, were demonstrated in his T cells. These findings suggest that his
      revertant T-cell mosaicism is responsible for OS phenotype switched from T-B-
      SCID.

PMID- 15845894
TI  - Direct recognition and lysis of leukemia cells by WT1-specific CD4+ T lymphocytes
      in an HLA class II-restricted manner.
AB  - Wilms tumor gene 1 product (WT1) has been recognized as an attractive target
      antigen of immunotherapy for various malignancies including leukemia. Because
      tumor-associated antigen-specific CD4+ T lymphocytes undoubtedly play an
      important role in the induction of an antitumor immune response, we attempted to
      generate WT1-specific CD4+ T lymphocytes in vitro and examined their antileukemia
      functions. A CD4+ T-cell line, designated NIK-1, which proliferated and produced
      Th1 cytokines specifically in response to stimulation with the WT1-derived
      peptide, WT1(337-347) LSHLQMHSRKH, in an HLA-DP5-restricted manner was
      established. NIK-1 exhibited cytotoxicity against HLA-DP5-positive, WT1
      expressing leukemia cells but did not lyse HLA-DP5-negative, WT1-expressing
      leukemia cells or HLA-DP5-positive, WT1-negative cells. NIK-1 did not inhibit
      colony formation by normal bone marrow cells of HLA-DP5-positive individuals.
      This is the first report to describe WT1-specific and HLA class II-restricted
      CD4+ T lymphocytes possessing direct cytotoxic activity against leukemia cells.

PMID- 15845895
TI  - Nuclear expression of BCL10 or nuclear factor kappa B helps predict Helicobacter
      pylori-independent status of low-grade gastric mucosa-associated lymphoid tissue
      lymphomas with or without t(11;18)(q21;q21).
AB  - The t(11;18)(q21;q21) translocation is a specific marker for Helicobacter pylori
      independent status of low-grade gastric mucosa-associated lymphoid tissue (MALT)
      lymphoma. However, there are no reliable markers to predict tumor response to H
      pylori eradication in patients without t(11;18)(q21;q21). Nuclear expression of
      BCL10 and nuclear factor kappa B (NF-kappaB) was recently found to be closely
      associated with H pylori-independent status of the high-grade counterpart of
      gastric MALT lymphoma, which usually lacks t(11;18)(q21;q21). This study examined
      whether these 2 markers can also predict H pylori-independent status of low-grade
      gastric MALT lymphomas without t(11; 18)(q21;q21). Sixty patients who underwent
      successful H pylori eradication for low-grade gastric MALT lymphomas were
      included. Forty-seven (78.3%) patients were negative for t(11;18)(q21;q21); among
      them, 36 (76.6%) were H pylori dependent and 11 (23.4%) were H pylori
      independent. Nuclear expression of BCL10 was significantly higher in H pylori
      independent than in H pylori-dependent tumors (8 of 11 [72.7%] vs 3 of 36 [8.3%];
      P < .001). Nuclear expression of NF-kappaB was also significantly higher in H
      pylori-independent than in H pylori-dependent tumors (7 of 11 [63.6%] vs 3 of 36
      [8.3%]; P < .001). Further, nuclear translocation of BCL10 and NF-kappaB was
      observed in 12 of the 13 patients with t(11;18)(q21;q21), and all these 12
      patients were H pylori independent. In summary, nuclear expression of BCL10 or NF
      kappaB is predictive of H pylori-independent status of low-grade gastric MALT
      lymphoma with or without t(11;18)(q21; q21).

PMID- 15845896
TI  - BK DNA viral load in plasma: evidence for an association with hemorrhagic
      cystitis in allogeneic hematopoietic cell transplant recipients.
AB  - We performed a case-control study to determine the association of BK plasma
      viremia with hemorrhagic cystitis (HC) in hematopoietic cell transplant (HCT)
      recipients. Thirty cases of HC (14 of which occurred after platelet engraftment
      with documented BK viruria [BK-HC]) were compared with matched controls. Weekly
      plasma samples were tested for BK virus DNA by polymerase chain reaction (PCR).
      BK viremia detected before or during the disease was independently associated
      with HC (adjusted odds ratio = 30, P < .001); BK viremia was even important
      before clinical symptoms of HC occurred (odds ratio = 11, P < .001). Cases of HC
      and BK-HC had a significantly higher peak of BK plasma viral load than controls.
      BK virus was detected by in situ hybridization in bladder biopsies of 2 cases
      with severe HC and long-lasting BK viremia. BK virus seems to play a role in the
      development of HC and quantitative detection of BK DNA in plasma appears to be a
      marker of BK virus disease in HCT recipients.

PMID- 15845897
TI  - PF4/heparin complexes are T cell-dependent antigens.
AB  - Heparin-induced thrombocytopenia (HIT) is a life-threatening, thrombotic disorder
      associated with development of anti-platelet factor 4 (anti-PF4)/heparin
      autoantibodies. Little is known about the antigenic and cellular requirements
      that initiate the immune response to these complexes. To begin to delineate
      mechanisms of autoantibody formation in HIT, we studied the immunizing effects of
      murine PF4 (mPF4)/heparin in mice with and without thymic function. Euthymic mice
      were injected with mPF4/heparin complexes, mPF4, heparin, or buffer. Mice
      injected with mPF4/heparin, but not mPF4 or heparin alone, developed heparin
      dependent autoantibodies that shared serologic and functional characteristics of
      human HIT antibodies, including preferential binding to mPF4/heparin complexes
      and causing heparin- and FcRgammaIIA-dependent platelet activation. In contrast,
      athymic mice did not develop HIT-like antibodies. Taken together, these studies
      establish that PF4/heparin complexes are highly immunogenic and elicit self
      reacting anti-PF4/heparin antibodies in a T cell-dependent manner.

PMID- 15845898
TI  - Immunomodulatory effects of HSV-2 infection on immature macaque dendritic cells
      modify innate and adaptive responses.
AB  - Herpes simplex viruses (HSV) infect human and murine dendritic cells (DCs) and
      interfere with their immunostimulatory functions in culture. HSV-2 infection
      increases human immunodeficiency virus (HIV) spread in patients, and DCs also
      promote HIV infection. We have studied these topics in rhesus macaque monocyte
      derived DCs (moDCs) to set the stage for future studies of these issues in
      animals. We provide the first evidence that macaque DCs become infected by HSV-2.
      Structural viral proteins (ICP5 [infected cell protein 5], glycoprotein D [gD],
      envelope) were detected in the cell periphery, and a functional protein (infected
      cell protein 8 [ICP8]) was predominantly found in the nucleus after infection.
      Infectious HSV-2 induced apoptotic death, decreased expression of HLA-DR, CD40,
      CD80, CD83, and CD86, and increased release of interleukin-6 (IL-6), tumor
      necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-1alpha (MIP
      1alpha) (CCL3), and RANTES (regulated on activation normal T cells expressed and
      secreted) (CCL5) but not IL-12 or interferon-alpha (IFN-alpha) by macaque DCs.
      This coincided with HSV-2-infected DCs stimulating weak T-cell responses,
      including impaired SIV-specific responses. Comparable HSV-2 protein expression,
      DC apoptosis, as well as membrane immunophenotype and functional modifications
      were observed in HSV-2-exposed human moDCs. Such HSV-2-induced modifications of
      macaque and human DCs could augment DC-driven immunodeficiency virus infection.
      This work affords the basis for future macaque studies to explore how HSV-2
      impacts the efficacy of strategies being developed to prevent HIV transmission.

PMID- 15845899
TI  - T/B lineage choice occurs prior to intrathymic Notch signaling.
AB  - Commitment of hemopoietic progenitors to the T-cell lineage is a crucial
      requirement for T-cell development, yet the timing and developmental cues
      regulating this process remain controversial. Here we have devised a technique to
      analyze the T-cell/B-cell lineage potential of precursors that have been
      recruited to the fetal mouse thymus but which have yet to contact the thymic
      epithelial microenvironment. We show that lymphoid progenitors arriving at the
      thymus are not bipotent T/B precursors, and provide evidence that intrathymic
      Notch signaling is not the mechanism determining T/B lineage choice in migrant
      precursors. Rather, we provide evidence that Notch signaling influences T/B
      lineage choice in lymphoid precursors through interactions with defined stromal
      components within the fetal liver. Collectively, our data redefine our
      understanding of the role and timing of Notch signaling in relation to lineage
      choices in lymphoid precursors.

PMID- 15845900
TI  - Osteopontin, a key component of the hematopoietic stem cell niche and regulator
      of primitive hematopoietic progenitor cells.
AB  - Although recent data suggests that osteoblasts play a key role within the
      hematopoietic stem cell (HSC) niche, the mechanisms underpinning this remain to
      be fully defined. The studies described herein examine the role in hematopoiesis
      of Osteopontin (Opn), a multidomain, phosphorylated glycoprotein, synthesized by
      osteoblasts, with well-described roles in cell adhesion, inflammatory responses,
      angiogenesis, and tumor metastasis. We demonstrate a previously unrecognized
      critical role for Opn in regulation of the physical location and proliferation of
      HSCs. Within marrow, Opn expression is restricted to the endosteal bone surface
      and contributes to HSC transmarrow migration toward the endosteal region, as
      demonstrated by the markedly aberrant distribution of HSCs in Opn-/- mice after
      transplantation. Primitive hematopoietic cells demonstrate specific adhesion to
      Opn in vitro via beta1 integrin. Furthermore, exogenous Opn potently suppresses
      the proliferation of primitive HPCs in vitro, the physiologic relevance of which
      is demonstrated by the markedly enhanced cycling of HSC in Opn-/- mice. These
      data therefore provide strong evidence that Opn is an important component of the
      HSC niche which participates in HSC location and as a physiologic-negative
      regulator of HSC proliferation.

PMID- 15845901
TI  - PEP005, a selective small-molecule activator of protein kinase C, has potent
      antileukemic activity mediated via the delta isoform of PKC.
AB  - Ingenol 3-angelate (PEP005) is a selective small molecule activator of protein
      kinase C (PKC) extracted from the plant Euphorbia peplus, whose sap has been used
      as a traditional medicine for the treatment of skin conditions including warts
      and cancer. We report here that PEP005 also has potent antileukemic effects,
      inducing apoptosis in myeloid leukemia cell lines and primary acute myeloid
      leukemia (AML) cells at nanomolar concentrations. Of importance, PEP005 did not
      induce apoptosis in normal CD34+ cord blood myeloblasts at up to 2-log
      concentrations higher than those required to induce cell death in primary AML
      cells. The effects of PEP005 were PKC dependent, and PEP005 efficacy correlated
      with expression of PKC-delta. The delta isoform of PKC plays a key role in
      apoptosis and is therefore a rational potential target for antileukemic
      therapies. Transfection of KG1a leukemia cells, which did not express PKC-delta
      or respond to PEP005, with enhanced green fluorescent protein (EGFP)-PKC-delta
      restored sensitivity to induction of apoptosis by PEP005. Our data therefore
      suggest that activation of PKC-delta provides a novel approach for treatment of
      acute myeloid leukemia and that screening for PKC-delta expression may identify
      patients for potential responsiveness to PEP005.

PMID- 15845903
TI  - Efficient marking of human cells with rapid but transient repopulating activity
      in autografted recipients.
AB  - Short-term hematopoietic reconstituting cells have been identified in mice,
      nonhuman primates, and among human cells that engraft xenogeneic hosts. We now
      present clonal marking data demonstrating a rapid but unsustained contribution of
      cultured human autografts to the initial phase of hematologic recovery in
      myeloablated patients. Three patients received transplants of granulocyte colony
      stimulating factor-mobilized autologous peripheral blood (PB) cells, of which a
      portion (8%-25% of the CD34+ cells) had been incubated in vitro with growth
      factors (5 days) and clinical grade LN retrovirus (3-5 days). More than 9% of the
      clonogenic and long-term culture-initiating cells harvested were transduced.
      Semiquantitative and linear amplification-mediated polymerase chain reaction
      analyses of serial PB samples showed that marked white blood cells appeared in
      all 3 patients within 11 days and transiently constituted up to 0.1% to 1% of
      those produced in the first month. However, within another 2 to 9 months, marked
      cells had permanently decreased to very low levels. Analysis of more than 50
      vector insertion sites showed none of the clones detected in the first month were
      active later. Eighty percent of inserts were located within or near genes, 2 near
      CXCR4. These findings provide direct evidence of cells with rapid but transient
      repopulating activity in patients and demonstrate their efficient transduction in
      vitro.

PMID- 15845904
TI  - Synergistic effect of thrombin on collagen-induced platelet procoagulant activity
      is mediated through protease-activated receptor-1.
AB  - OBJECTIVE: In the blood coagulation process, the rate of thrombin formation is
      critically dependent on phosphatidylserine (PtdSer) at the surface of activated
      platelets. Thrombin synergistically enhances the collagen-induced platelet
      procoagulant response. The objective of this study is to elucidate the mechanism
      of this synergistic action with a focus on the intracellular Ca2+ concentration
      ([Ca2+]i) and the various platelet receptors for thrombin. METHODS AND RESULTS:
      We demonstrate that procoagulant activity is related to a sustained increased
      [Ca2+]i, which in turn depends on extracellular Ca2+ influx. Increased PtdSer
      exposure coincides with increased [Ca2+]i and was observed in a subpopulation
      (approximately 14%) of the platelets after stimulation with thrombin plus
      collagen. 2D2-Fab fragments against the thrombin binding site on GPIbalpha made
      clear that this receptor did not signal for platelet procoagulant activity.
      Inhibition of protease-activated receptor 1 (PAR-1) and PAR-4 by selective
      intracellular inhibitors and selective desensitization of these receptors
      revealed that PAR-1, but not PAR-4, activation is a prerequisite for both
      sustained elevations in [Ca2+]i and procoagulant activity induced by collagen
      plus thrombin. CONCLUSIONS: The interaction of thrombin with PAR-1 mediates a
      synergistic effect on collagen-induced procoagulant activity by inducing a
      sustained elevation in [Ca2+]i in a subpopulation of platelets.

PMID- 15845902
TI  - Impaired IL-4 and c-Maf expression and enhanced Th1-cell development in Vav1
      deficient mice.
AB  - Although c-Maf is crucial for Th2 differentiation and production of interleukin 4
      (IL-4), its regulation is poorly understood. We report that Vav1-/- CD4+ T cells
      display deficient T-cell receptor (TCR)/CD28-induced IL-4 and c-Maf expression
      and, conversely, enhanced interferon gamma (IFN-gamma) production and T-bet
      expression (even when cultured under Th2-polarizing conditions), but intact
      expression of other Th2 cytokines and GATA-3. Up-regulation of c-Maf was
      dependent on Ca2+/nuclear factor of activated T cell (NFAT) and, together with IL
      4 production, could be rescued in Vav1-/- T cells by Ca2+ ionophore. Deficient IL
      4 production was restored by retrovirus-mediated Vav1 expression, but only
      partially by retroviral c-Maf expression. Similar IL-4 --> IFN-gamma skewing was
      observed in intact, antigen-primed Vav1-/- mice. Thus, Vav1 is selectively
      required for IL-4 and c-Maf expression, a requirement reflecting, at least in
      part, the dependence of c-Maf expression on Ca2+/NFAT signaling.

PMID- 15845906
TI  - Platelet-leukocyte interaction and platelet activation in acute stroke with and
      without preceding infection.
AB  - OBJECTIVE: Acute coronary syndromes and ischemic cerebral stroke share
      similarities regarding elevated platelet activation. In coronary syndromes, the
      importance of inflammation with platelet-leukocyte interaction has been
      demonstrated. Recent infection is an established risk factor for ischemic stroke;
      the role of platelet-leukocyte interaction in these patients had not been
      investigated. METHODS AND RESULTS: Using a flow cytometric assay we investigated
      58 stroke patients, 21 with and 37 without infection 1 week before acute cerebral
      ischemia, and compared them to 58 controls with regard to platelet-leukocyte
      aggregation and platelet activation on admission and on day 7. Patients with
      previous infection were significantly up-regulated with regard to platelet
      activation and platelet-leukocyte aggregation compared with patients without
      infection. On day 7, these increases in the postinfective group had drawn level
      with the lower values of the other patients. As reported previously, recent
      infection was associated with a more severe postischemic deficit. CONCLUSIONS:
      These results suggest an important role of intercellular platelet-leukocyte
      interaction in the pathophysiology of acute cerebral ischemia which may also
      contribute to the increased incidence and clinical severity of ischemic stroke
      following infection. This may lead to therapeutic considerations of blocking
      intercellular adhesion molecules like P-selectin or the P-selectin glycoprotein
      ligand.

PMID- 15845905
TI  - Porphyromonas gingivalis bacteremia induces coronary and aortic atherosclerosis
      in normocholesterolemic and hypercholesterolemic pigs.
AB  - OBJECTIVES: The aim of this study was to determine whether recurrent intravenous
      injections with Porphyromonas gingivalis (P gingivalis), mimicking periodontitis
      associated bacteremia, promotes coronary artery and aortic atherosclerosis in
      pigs. METHODS AND RESULTS: Pigs (n=36) fed low- or high-fat chow were divided
      into P gingivalis-sensitized and P gingivalis-challenged groups or P gingivalis
      sensitized controls and saline-treated controls. Pigs were sensitized with 10(9)
      killed P gingivalis subcutaneously. Four weeks later all sensitized pigs in the
      group to be challenged started intravenous injections thrice weekly for 5 months
      with 10(6) to 10(7) colony forming units of P gingivalis while controls received
      saline. Anti-P gingivalis antibody, serum cholesterol, and complete blood counts
      were assayed monthly. Pigs were euthanized 2 weeks after the last injection, and
      coronary arteries and aortas were analyzed by histomorphometry and
      immunohistochemistry. Anti-P gingivalis antibody was increased by P gingivalis
      exposure. P gingivalis-challenged pigs developed a significantly greater amount
      of coronary and aortic atherosclerosis than controls in the normocholesterolemic
      group and nearly significant in the hypercholesterolemic group. P gingivalis was
      detected by polymerase chain reaction in arteries from most (94%, 16 of 17) P
      gingivalis-challenged pigs but not controls. CONCLUSIONS: Recurrent P gingivalis
      bacteremia induces aortic and coronary lesions consistent with atherosclerosis in
      normocholesterolemic pigs and increases aortic and coronary atherosclerosis in
      hypercholesterolemic pigs.

PMID- 15845907
TI  - At least 2 distinct pathways generating reactive oxygen species mediate vascular
      cell adhesion molecule-1 induction by advanced glycation end products.
AB  - OBJECTIVE: The interaction of advanced glycation end products (AGEs) with their
      main receptor RAGE in endothelial cells induces intracellular generation of
      reactive oxygen species (ROS) and the expression of vascular cell adhesion
      molecule (VCAM)-1. We investigated the role of distinct sources of ROS, including
      the mitochondrial electron transport chain, NAD(P)H oxidase, xanthine oxidase,
      and arachidonic acid metabolism, in AGE-induced VCAM-1 expression. METHODS AND
      RESULTS: The induction of ROS and VCAM-1 by AGEs in cultured human umbilical vein
      endothelial cells was specifically blocked by an anti-RAGE antibody. The
      inhibition of NAD(P)H oxidase by apocynin and diphenylene iodonium, and of the
      mitochondrial electron transport system at complex II by thenoyltrifluoroacetone
      (TTFA), significantly inhibited both AGE-induced ROS production and VCAM-1
      expression, whereas these effects were potentiated by rotenone and antimycin A,
      specific inhibitors of mitochondrial complex I and III, respectively. The
      inhibition of Cu/Zn superoxide dismutase inhibited both ROS and VCAM-1 induction,
      indicating that H2O2 by this source is involved as a mediator of VCAM-1
      expression by AGEs. CONCLUSIONS: Altogether, these results demonstrate that ROS
      generated by both NAD(P)H-oxidase and the mitochondrial electron transport system
      are involved in AGE signaling through RAGE, and indicate potential targets for
      the inhibition of the atherogenic signals triggered by AGE-RAGE interaction.

PMID- 15845908
TI  - High prevalence of circulating CD4+CD28- T-cells in patients with small abdominal
      aortic aneurysms.
AB  - OBJECTIVE: To assess the possible role of proinflammatory CD28- T cells in
      abdominal aortic aneurysms (AAAs). Animal studies and human tissue studies
      suggest a role for interferon (IFN)-gamma-producing T cells in the development
      and progression of AAAs. METHODS AND RESULTS: Fluorescence-activated cells sorter
      analysis of peripheral blood samples and measurement of AAA size using sonography
      were performed in 101 AAA patients and 38 healthy controls. Peripheral
      percentages of CD28- T cells of the CD3+CD4+ and the CD3+CD8+ were enriched in
      AAA patients with 7.8+/-8.8% and 41.9+/-15.7% compared with healthy controls with
      2.2+/-6.1% and 24.9+/-15.5%, respectively (P=0.002 and P<0.001, respectively).
      Both CD4+CD28- and CD8+CD28- T cells produced large amounts of IFN-[gamma] and
      perforin. Patients with small AAAs (<4 cm) showed higher peripheral levels of
      CD4+CD28- T cells than those with larger AAAs (P=0.025). Immunohistological
      examinations revealed 39.1+/-17.2% CD4+CD28- and 44.0+/-13.8% CD8+CD28- in AAA
      tissue specimens with inflammatory infiltratestes. CONCLUSIONS: IFN-gamma- and
      perforin-producing CD28- T cells are present in the periphery and the vessel wall
      of a majority of AAAs. This observation in humans favors the concept of a T cell
      mediated pathophysiology of AAAs, especially during the early development of
      AAAs.

PMID- 15845910
TI  - Knockdown of hepatic ABCA1 by RNA interference decreases plasma HDL cholesterol
      levels and influences postprandial lipemia in mice.
AB  - OBJECTIVE: To investigate the impact of hepatic ABCA1 on systemic lipoprotein
      metabolism in vivo by an adenovirus-mediated RNA interference approach. METHODS
      AND RESULTS: Efficiency of plasmid-based small interference RNA (siRNA)-induced
      knockdown of cotransfected murine ATP binding cassette transporter A1 (mABCA1) in
      HEK-293 cells was judged by RT-polymerase chain reaction, immunofluorescence, and
      Western blot analysis. The most effective plasmid was used to generate a
      recombinant adenovirus as a tool to selectively downregulate ABCA1 expression in
      mouse liver (C57BL/6). In comparison to controls, Western blot analysis from
      liver membrane proteins of Ad-anti-ABCA1 infected mice resulted in an
      approximately 50% reduction of endogenous ABCA1 and a clear upregulation of
      apolipoprotein E. Fast protein liquid chromatography analysis of plasma revealed
      that hepatic ABCA1 protein reduction was associated with an approximately 40%
      decrease of HDL cholesterol and a reduction of HDL-associated apolipoprotein A-I
      and E. In the fasted state, other lipoprotein classes were not affected. To
      analyze the influence of ABCA1 downregulation on postprandial lipemia, infected
      mice were given a gastric load of radiolabeled trioleate in olive oil. In Ad-anti
      ABCA1 infected mice, the postprandial increase of chylomicrons and chylomicron
      associated apolipoproteins B and E was significantly reduced as compared with
      controls. CONCLUSIONS: Hepatic ABCA1 contributes to HDL plasma levels and
      influences postprandial lipemia.

PMID- 15845909
TI  - D-4F and statins synergize to render HDL antiinflammatory in mice and monkeys and
      cause lesion regression in old apolipoprotein E-null mice.
AB  - OBJECTIVE: We tested for synergy between pravastatin and D-4F by administering
      oral doses of each in combination that were predetermined to be ineffective when
      given as single agents. METHODS AND RESULTS: The combination significantly
      increased high-density lipoprotein (HDL)-cholesterol levels, apolipoprotein
      (apo)A-I levels, paraoxonase activity, rendered HDL antiinflammatory, prevented
      lesion formation in young (79% reduction in en face lesion area; P<0.0001) and
      caused regression of established lesions in old apoE null mice (ie, mice
      receiving the combination for 6 months had lesion areas that were smaller than
      those before the start of treatment (P=0.019 for en face lesion area; P=0.004 for
      aortic root sinus lesion area). After 6 months of treatment with the combination,
      en face lesion area was 38% of that in mice maintained on chow alone; P<0.00004)
      with a 22% reduction in macrophage content in the remaining lesions (P=0.001),
      indicating an overall reduction in macrophages of 79%. The combination increased
      intestinal apoA-I synthesis by 60% (P=0.011). In monkeys, the combination also
      rendered HDL antiinflammatory. CONCLUSIONS: These results suggest that the
      combination of a statin and an HDL-based therapy may be a particularly potent
      treatment strategy.

PMID- 15845911
TI  - A locus on chromosome 2 influences levels of tissue factor pathway inhibitor:
      results from the GAIT study.
AB  - OBJECTIVE: Levels of tissue factor pathway inhibitor (TFPI) have been associated
      with arteriosclerosis and thrombotic disease. Although a genetic component to
      variation in TFPI levels is well-documented, no systematic genome-wide screens
      have been conducted to localize genes influencing levels of TFPI. METHODS AND
      RESULTS: We studied TFPI levels in 397 individuals in 21 Spanish families
      participating in the Genetic Analysis of Idiopathic Thrombosis (GAIT) study.
      Twelve families were selected through a proband with idiopathic thrombosis and 9
      were ascertained without regard to phenotype. A genome scan was performed using
      microsatellite markers spaced at approximately 10 cM intervals. Standard
      multipoint variance component linkage methods were used. The heritability of TFPI
      levels was 0.52 (P<0.0001), with no evidence for shared household effects. In the
      genome screen, only 1 LOD score >2 was observed. On chromosome 2q, the maximum
      multipoint LOD score was 3.52 near marker D2S1384. This is near the structural
      gene for TFPI, which is located at 2q32. In follow-up association analyses,
      marginal evidence of association (P=0.04) was observed with the TFPI promoter
      variant C-399T. CONCLUSIONS: These results suggest that polymorphisms in and
      around the TFPI structural gene may be the major genetic determinants of
      variation in TFPI levels.

PMID- 15845912
TI  - Difference in matrix-degrading protease expression and activity between thrombus
      free and thrombus-covered wall of abdominal aortic aneurysm.
AB  - OBJECTIVE: It has been suggested that the intraluminal thrombus of abdominal
      aortic aneurysms (AAAs) predisposes for AAA rupture. Here, we examined the
      possibility that the intraluminal thrombus influences expression and activity of
      matrix-degrading proteases in the AAA wall. METHODS AND RESULTS: Twenty patients
      undergoing elective repair of AAAs were included. From each patient, specimens
      from both thrombus-covered and thrombus-free wall were taken for analysis. Gene
      arrays and quantitative real-time polymerase chain reaction showed that matrix
      metalloproteinase (MMP)-1, -7, -9, and -12 expressions were upregulated in the
      thrombus-free wall compared with the thrombus-covered wall. Immunohistochemistry
      confirmed the differential expression of MMP-9 but also localized MMP-9 to the
      interface between the thrombus and the underlying vessel wall. MMP-9 expression
      was colocalized with the presence of macrophages. Similar expression patterns
      were observed for urokinase plasminogen activator (uPA), uPA receptor, and
      plasminogen activator inhibitor-1. Gelatinase activity was detected in the same
      regions as MMP-9 protein expression, ie, within the thrombus-free wall and in the
      interface between the thrombus and the underlying wall. CONCLUSIONS: The present
      work demonstrates that protease expression and activity differs within the
      aneurysm wall. The source and activity of the proteases responsible for the
      degradation of the thrombus-covered wall need to be further determined.

PMID- 15845913
TI  - Calcification of advanced atherosclerotic lesions in the innominate arteries of
      ApoE-deficient mice: potential role of chondrocyte-like cells.
AB  - OBJECTIVE: Advanced atherosclerotic lesions in the innominate arteries of chow
      fed apolipoprotein E-deficient mice become highly calcified with 100% frequency
      by 75 weeks of age. The time course, cell types, and mechanism(s) associated with
      calcification were investigated. METHODS AND RESULTS: The deposition of
      hydroxyapatite is preceded by the formation of fibro-fatty nodules that are
      populated by cells that morphologically resemble chondrocytes. These cells are
      spatially associated with small deposits of hydroxyapatite in animals between 45
      and 60 weeks of age. Immunocytochemical analyses with antibodies recognizing
      known chondrocyte proteins show that these cells express the same proteins as
      chondrocytes within developing bone. Histological and electron microscopic
      analyses of lesions from animals between 45 and 60 weeks of age show that the
      chondrocyte-like cells are surrounded by dense connective tissue that stains
      positive for type II collagen. Nanocrystals of hydroxyapatite can be seen within
      matrix vesicles derived from the chondrocyte-like cells. In mice between 75 and
      104 weeks of age, the lesions have significantly reduced cellularity and contain
      large calcium deposits. The few remaining chondrocyte-like cells are located
      adjacent to or within the large areas of calcification. CONCLUSIONS:
      Calcification of advanced lesions in chow-fed apolipoprotein E-deficient mice
      occurs reproducibly in mice between 45 and 75 weeks of age. The deposition of
      hydroxyapatite is mediated by chondrocytes, which suggests that the mechanism of
      calcification may in part recapitulate the process of endochondral bone
      formation.

PMID- 15845914
TI  - Postmenopausal hormone therapy: from monkey glands to transdermal patches.
AB  - The climacteric is not a condition of the modern age, although with increased
      life expectancy over the centuries, more women will experience this physiological
      transition. As women are living longer there is a greater expectation that good
      health will be maintained through to the late decade. Thus the potential long
      term adverse health consequences of using hormonal therapies (HTs) to alleviate
      menopausal symptoms are of considerable concern for women and medical
      practitioners. This concern is often the basis for a decision whether or not to
      use HT. We have reviewed the history of knowledge of the menopause and the
      development of HT for the treatment of climacteric complaints. We have also
      summarised the current evidence for specific benefits and risks of HT. Data
      indicate that postmenopausal HT is appropriate for the management of vasomotor
      symptoms, but that HT should not be prescribed for the prevention of
      cardiovascular disease or dementia. HT does prevent bone loss and osteoporotic
      fracture; however, use for this purpose remains controversial. The risk of breast
      cancer with HT varies according to the preparation used, such that oestrogen
      without concurrent progestin appears to convey little, or possibly even no
      significant breast cancer risk. There is insufficient information regarding the
      long-term use of non-oral HT, low-dose HT or novel compounds such as tibolone or
      the selective oestrogen receptor modulators with respect to breast cancer and
      cardiovascular risk for specific recommendations to be made.

PMID- 15845915
TI  - Role of oestrogen in the regulation of bone turnover at the menarche.
AB  - The rise in oestrogen levels at menarche in girls is associated with a large
      reduction in bone turnover markers. This reduction reflects the closure of the
      epiphyseal growth plates, the reduction in periosteal apposition and endosteal
      resorption within cortical bone, and in bone remodelling within cortical and
      cancellous bone. Oestrogen promotes these changes, in part, by promoting
      apoptosis of chondrocytes in the growth plate and osteoclasts within cortical and
      cancellous bone. The period of early puberty is associated with an increased risk
      of fracture, particularly of the distal forearm, and this may be related to the
      high rate of bone turnover. A late menarche is a consistent risk factor for
      fracture and low bone mineral density in the postmenopausal period; models that
      might explain this association are considered.

PMID- 15845916
TI  - Specific binding of 4-hydroxyestradiol to mouse uterine protein: evidence of a
      physiological role for 4-hydroxyestradiol.
AB  - There are several indications of a possible physiological role for 4
      hydroxyestradiol (4-OHE(2)) in hormone-responsive tissues. To examine a hormonal
      activity of 4-OHE(2), we have studied the binding of (3)H-labeled 4-OHE(2) to
      mouse uterine cytosolic protein. In uteri of 3-week-old mice, total binding was
      319.4 +/- 13.9 fmol/mg protein. Binding in the presence of excess unlabeled 4
      OHE(2) dropped to 82.1 +/- 1.7 fmol/mg protein, whereas 214.6 +/- 9.4 fmol/mg
      protein bound while incubating in an excess of unlabeled 17beta-estradiol (E(2)).
      The difference between the two binding values in the presence of excess steroid
      (132.5 +/- 11.1 fmol/mg protein) is taken as selective binding of 4-OHE(2) to a
      specific protein. In mice older than 4 weeks, the specific 4-OHE(2) binding
      declined: 32.0 +/- 4.0 fmol/mg protein at 8 weeks, 54.8 +/- 6.3 fmol/mg protein
      at 12 weeks and 54.6 +/- 5.2 fmol/mg protein at 9 months. Of other organs tested
      (liver, kidney, lung and whole brain) only lung showed significant selective
      binding of 4-OHE(2). When E(2)-binding sites are blocked, binding follows first
      order kinetics, yielding a dissociation constant (K(d)) value of 11.8 +/- 2.1 nM.
      The specific binding of 4-OHE(2) was not inhibited by any other steroids or
      estrogen metabolites that were tested, except for 2-hydroxyestradiol (2-OHE(2)),
      which displayed competitive inhibition of 4-OHE(2) binding with an inhibition
      constant (K(i)) value of 98.2 +/- 12.6 nM. These results lead us to conclude that
      4-OHE(2) binds to a specific binding protein, distinct and different from binding
      to estrogen receptors (ERalpha and ERbeta). The physiological role of this
      binding remains to be elucidated.

PMID- 15845917
TI  - Suppression of experimental autoimmune encephalomyelitis using estrogen receptor
      selective ligands.
AB  - Estrogens have been shown to modulate disease activity in experimental autoimmune
      encephalomyelitis (EAE), the mouse model for multiple sclerosis. Consistent with
      these findings, the severity of disease is reduced in pregnant women with
      multiple sclerosis when levels of estrogens are high. Estrogens bind to two known
      estrogen receptors (ER), ERalpha and ERbeta. The relative contribution of these
      receptors to estrogen-mediated suppression of EAE was explored using ER-selective
      ligands. The ER antagonist ICI 182 780 reversed the suppressive effects of 17beta
      estradiol (E2), demonstrating that the protective effects of E2 on disease are
      dependent upon ER signaling. Treatment of SJL mice with the ERalpha-selective
      agonist proteolipid protein (PPT) prior to the induction of disease resulted in
      suppression of clinical symptoms of disease, whereas treatment with an ERbeta
      selective agonist (WAY-202041) had no effect. Treatment of mice with PLP peptide
      139-151 (PPT) was also associated with decreased immune responses associated with
      disease. Consistent with its lack of effect on disease, the ERbeta agonist had
      minimal effects on immune responses. The use of selective estrogen receptor
      modulators (SERMs) in this model was also explored, and we show that raloxifene
      and WAY-138923 were also effective in suppressing disease. These results
      demonstrate the beneficial effects of estrogen receptor ligands, in particular
      ERalpha-selective ligands, and may have implications in the development of
      therapeutic strategies for multiple sclerosis.

PMID- 15845919
TI  - The cellular repressor of E1A-stimulated genes mediates glucocorticoid-induced
      loss of the type-2 IGF receptor in ileal epithelial cells.
AB  - Glucocorticoids induce hypertrophy of the neonatal ileal mucosa but the molecular
      mechanisms behind this growth induction remain poorly understood. Ileal
      epithelial cells (IECs) are dependent upon IGF-II for proliferation both in vivo
      and in culture. The type-2 IGF receptor (IGFR-2) is a lysosomal transport protein
      that attenuates IGF-II-driven growth and is highly abundant in the ileum. The
      cellular repressor of E1A-stimulated genes (CREG) is a secreted
      phosphoglycoprotein that affects cell fate via ligand binding with IGFR-2,
      although the mechanism by which it does so is unknown. We hypothesized that
      glucocorticoids might facilitate IGF-mediated hypertrophy through CREG-mediated
      degradation of IGFR-2. To test this hypothesis, confluent rat IECs (IEC-18) were
      cultured for 72 h with or without dexamethasone (DEX) and harvested for Western
      blot, immunocytochemistry, gene array and CREG immunoneutralization experiments.
      IGFR-2 and CREG immunohistochemistry were also performed in archived ileal
      specimens from control and DEX-exposed newborn mice and extremely premature
      infants to investigate in vivo and clinical relevance. DEX exposure was found to
      diminish IGFR-2 immunolocalization in cultured rat IECs, newborn mouse ileal
      mucosa and human neonatal ileal mucosa. Gene array data indicated that IGFR-2
      expression was unchanged with DEX treatment, suggesting a mechanism of protein
      degradation. CREG immunolocalization and abundance was found to be increased by
      DEX and immunoneutralization of CREG resulted in the abolition of IGFR-2
      degradation. We have concluded that CREG is a secreted mediator by which DEX
      induces degradation of IGFR-2 and speculate that this is a fundamental mechanism
      of mucosal growth induction.

PMID- 15845918
TI  - Dexamethasone-induced intrauterine growth restriction impacts the placental
      prolactin family, insulin-like growth factor-II and the Akt signaling pathway.
AB  - Intrauterine growth restriction (IUGR) is a major cause of perinatal death and
      neonatal morbidity and mortality. There are numerous causes of IUGR.
      Glucocorticoid-induced IUGR is highly relevant because administration of
      synthetic glucocorticoids, principally dexamethasone, to women threatened by
      premature labor is widely used in clinical practice. Fetal growth is directly
      related to placental growth and development. In this report, we analyzed the
      effect of dexamethasone on placental development in the rat. Dexamethasone
      administered between days 13 and 20 of pregnancy not only induced IUGR but also
      decreased placental mass by approximately 50%. Impaired placental development was
      associated with dysregulated placental prolactin (PRL) family and insulin-like
      growth factor-II (IGF-II) gene expression. Furthermore, there was a significant
      decrease in the activation of Akt/protein kinase B in the junctional zone of the
      placenta, as assessed by the phosphorylation status of Akt and the pro-apoptotic
      protein BAD, a downstream target of the Akt signaling pathway. Such changes are
      consistent with increases in indices of apoptosis, including increased cleavage
      of poly(ADP-ribose) polymerase (PARP) in the junctional zone of the placenta of
      dexamethasone-treated rats. In summary, dexamethasone-induced IUGR is associated
      with placental insufficiency, including dysregulated placental hormone/cytokine
      gene expression and down-regulation of the IGF-II/Akt signaling pathway resulting
      in increases in indices of placental apoptosis.

PMID- 15845920
TI  - Insulin and IGF-I stimulate the formation of the eukaryotic initiation factor 4F
      complex and protein synthesis in C2C12 myotubes independent of availability of
      external amino acids.
AB  - The objective of this study was to investigate the effect of insulin and IGF-I on
      protein synthesis and translation initiation in C2C12 myotubes in nutrient
      deprived Dulbecco's phosphate buffered saline (DPBS). The results showed that
      insulin and IGF-I increased protein synthesis by 62% and 35% respectively in
      DPBS, and the effect was not affected by rapamycin, but was blocked by LY294002.
      Insulin and IGF-I stimulated eukaryotic initiation factor 4E (eIF4E) binding
      protein (4EBP1) phosphorylation in a dose-dependent manner, and the stimulation
      was independent of availability of external amino acids. Both LY294002 and
      rapamycin blocked the insulin and IGF-I-induced increases in 4EBP1
      phosphorylation. The results also showed that insulin and IGF-I were able to
      stimulate PKB/Akt phosphorylation, glycogen synthase kinase (GSK) 3beta
      phosphorylation and mTOR phosphorylation in DPBS. Insulin and IGF-I increased the
      amount of eIF4G associated with eIF4E in nutrient-deprived C2C12 myotubes. The
      amount of 4EBP1 associated with eIF4E was decreased after insulin or IGF-I
      stimulation. We conclude that in C2C12 myotubes, insulin and IGF-I may regulate
      protein synthesis and translation initiation independent of external amino acid
      supply via the phosphatidylinositol-3 kinase-PKB/Akt-mTOR pathway.

PMID- 15845921
TI  - Alterations in net glucose uptake and in the pancreatic B-cell GLUT2 transporter
      induced by diazoxide and by secretory stimuli.
AB  - The pancreatic B-cell GLUT2 transporter and glucose metabolism were examined in
      isolated rat islets subjected to treatments affecting insulin secretion.
      Diazoxide was used to inhibit, while glipizide or depolarization of the plasma
      membrane with a high extracellular K(+) concentration were used to stimulate
      insulin release in short-term experiments. Islet GLUT2 and insulin were
      determined by quantitative immunohistochemistry and GLUT2 was also determined by
      Western blot analysis. Islet net glucose uptake and glucose oxidation were
      measured using radioactively labelled glucose. Exposure of the islets to
      diazoxide was associated with a marked increase in the B-cell plasma membrane
      staining for GLUT2 and increased net glucose uptake. Glucose oxidation was not
      changed, which may reflect a lowered energy requirement. Conversely, islets
      subjected to a stimulated insulin secretion with glipizide or a high
      extracellular K(+) concentration showed a reduced staining of the GLUT2
      transporter. The net glucose uptake and glucose oxidation were also reduced. In
      islets exposed to the high K(+) concentration no change in the molecular weight
      or phosphorylation of GLUT2 was observed but a lesser amount of the transporter
      was found by Western blot analysis. Thus, GLUT2 and glucose uptake in the
      pancreatic B-cell are modified by the secretory process, which suggests that
      changes in the glucose transporter have a functional role in normal B-cell
      physiology.

PMID- 15845922
TI  - Increased SH2-Bbeta content and membrane association in transgenic mice
      overexpressing GH.
AB  - Transgenic mice overexpressing GH present a marked GH signaling desensitization,
      reflected by low basal phosphorylation levels of the tyrosine kinase JAK2, and
      signal transducer and activator of transcription-5 (STAT5) and a lack of response
      of these proteins to a high GH dose. To evaluate the mechanisms involved in the
      regulation of JAK2 activity by high GH levels in vivo, the content and
      subcellular distribution of SH2-Bbeta were studied in GH-overexpressing
      transgenic mice. SH2-B is a member of a conserved family of adapter proteins
      characterized by the presence of a C-terminal SH2 domain, a central pleckstrin
      homology (PH) domain, and an N-terminal proline rich region. The isoform SH2
      Bbeta modulates JAK2 activity by binding to the phosphorylated enzyme, further
      increasing its activity. However, it may also interact with non-phosphorylated
      inactive JAK2 via lower affinity binding sites, preventing abnormal activation of
      the kinase. SH2-Bbeta may also function as an adapter protein, acting as a GH
      signaling mediator. We now report that, in an animal model of GH excess in which
      JAK2 is not phosphorylated, although it is increased in the membrane-fraction,
      both the level of SH2-Bbeta, and especially its association to membranes, are
      augmented (67% and 13-fold vs normal mice values respectively), suggesting SH2
      Bbeta could modulate JAK2 activity in vivo.

PMID- 15845923
TI  - Chronic treatment with exendin(9-39)amide indicates a minor role for endogenous
      glucagon-like peptide-1 in metabolic abnormalities of obesity-related diabetes in
      ob/ob mice.
AB  - Glucagon-like peptide-1 (GLP-1) is a potent insulinotropic hormone proposed to
      play a role in both the pathophysiology and treatment of type 2 diabetes. This
      study has employed the GLP-1 receptor antagonist, exendin-4(9-39)amide (Ex(9-39))
      to evaluate the role of endogenous GLP-1 in genetic obesity-related diabetes and
      related metabolic abnormalities using ob/ob and normal mice. Acute in vivo
      antagonistic potency of Ex(9-39) was confirmed in ob/ob mice by blockade of the
      insulin-releasing and anti-hyperglycaemic actions of intraperitoneal GLP-1. In
      longer term studies, ob/ob mice were given once daily injections of Ex(9-39) or
      vehicle for 11 days. Feeding activity, body weight, and both basal and glucose
      stimulated insulin secretion were not significantly affected by chronic Ex(9-39)
      treatment. However, significantly elevated basal glucose concentrations and
      impaired glucose tolerance were evident at 11 days. These disturbances in glucose
      homeostasis were independent of changes of insulin sensitivity and reversed by
      discontinuation of the Ex(9-39) for 9 days. Similar treatment of normal mice did
      not affect any of the parameters measured. These findings illustrate the
      physiological extrapancreatic glucose-lowering actions of GLP-1 in ob/ob mice and
      suggest that the endogenous hormone plays a minor role in the metabolic
      abnormalities associated with obesity-related diabetes.

PMID- 15845924
TI  - Leptin receptor expression and in vitro leptin actions on prostaglandin release
      and nitric oxide synthase activity in the rabbit oviduct.
AB  - In this study, we have examined the presence and the distribution of receptors
      for leptin (Ob-R) in the oviduct of rabbits, and the effects of leptin on the
      release of prostaglandin (PG) F2alpha and PGE2 and on the activity of nitric
      oxide (NO) synthase (NOS) by oviducts cultured in vitro. Rabbits were killed
      during the follicular phase and the oviducts were incubated in vitro with leptin,
      PGF2alpha, PGE2, NO donor and inhibitors of NOS and cyclo-oxigenase (COX). Using
      immunohistochemistry, Ob-R-like positive reaction was observed only in the
      cytoplasm of secretory cells, having stronger intensity in the infundibulum and
      ampulla tracts than in the isthmus. Both leptin and NO donor inhibited PGE2
      release, whereas they enhanced PGF2alpha release; NOS inhibitor alone or with
      leptin increased PGE2 and decreased PGF2alpha production; NOS activity was
      enhanced by leptin, while PGs did not affect this enzyme. This study suggests
      that the oviduct could be a potential target for endocrine regulation by leptin,
      whose circulating levels may act as a metabolic signal modulating oviductal PG
      release through mediation of the NOS/NO system.

PMID- 15845925
TI  - Developmentally defined regulation of thyroid hormone metabolism by
      glucocorticoids in the rat.
AB  - Glucocorticoids are known regulators of thyroid function in vertebrates. In birds
      they have clear tissue-specific and age-dependent effects on thyroid hormone
      metabolism. In mammals, however, few studies exist addressing these aspects using
      an in vivo model system. We therefore set out to examine the acute effects of a
      single dose of dexamethasone (DEX) on plasma 3,5,3'-tri-iodothyronine (T(3)) and
      thyroxine (T(4)) levels, as well as on the activity of the different deiodinases
      in liver, kidney and brain in the developing rat. In 20-day-old fetuses (E20),
      glucocorticoids had no effects on circulating thyroid hormone levels despite
      their clear effects on hepatic and renal deiodinases, thereby indicating that
      under these conditions circulating thyroid hormone levels are more dependent on
      thyroidal secretion than on peripheral deiodination. In contrast, in 5-day-old
      rat pups, DEX did not seem to have any effects on hepatic and renal T(3)
      production (via the type I deiodinase), whereas type III deiodinase (D3) activity
      in both these tissues increased significantly. These observations therefore
      suggested that the DEX-induced increase in circulating T(3) levels is a direct
      consequence of the increase in plasma T(4) levels. In 12-day-old pups (P12),
      however, the main effect of glucocorticoids on circulating levels was by
      increasing inner ring deiodination T(3) through induction of D3 in both liver and
      kidney. Finally, in the brain, glucocorticoids stimulated thyroid hormone
      activity only during a short period of time (between E20 and P12) that largely
      overlaps with the transient window in time during which brain development is
      thyroid hormone sensitive. This was in contrast to the E20 and P12 brain, where
      the glucocorticoid-induced changes in type II deiodinase and D3 seemed to favor a
      status quo in local T(3) availability.

PMID- 15845926
TI  - Hypomethylation in the promoter region of POMC gene correlates with ectopic
      overexpression in thymic carcinoids.
AB  - The ectopic ACTH syndrome is caused by abnormal expression of the POMC gene
      product arising from non-pituitary tumors in response to the ectopic activation
      of the pituitary-specific promoter of this gene. It has been proved that
      methylation of the CpG island in the promoter region is associated with silencing
      of some genes. Using bisulphite sequencing, we identified hypermethylation in the
      5' promoter region of the POMC gene in three normal thymuses and one large cell
      lung cancer, and hypomethylation in five thymic carcinoid tumors resected from
      patients with ectopic ACTH syndrome. The region undergoing hypermethylation was
      narrowed to coordinates -417 to -260 of the POMC promoter. Furthermore, we
      observed that the levels of POMC expression correlated with the methylation
      density at -417 to -260 bp across the E2 transcription factor binding region of
      the POMC promoter. It is concluded that hypomethylation of the POMC promoter in
      thymic carcinoids correlates with POMC overexpression and the ectopic ACTH
      syndrome.

PMID- 15845927
TI  - Sexual dysfunction in males with chronic hepatitis C and antiviral therapy:
      interferon-induced functional androgen deficiency or depression?
AB  - Decrease of libido and erectile dysfunction are reported by male patients during
      antiviral therapy of chronic hepatitis C, but therapy-associated underlying
      factors for sexual dysfunction are not well defined. To assess putative
      contributions of interferon-induced sex hormone changes to sexual dysfunction, we
      prospectively investigated changes in free testosterone, total testosterone,
      dehydroepiandrosterone sulfate, prolactin, sex hormone-binding globulin, FSH and
      LH levels and psychometric self-assessment scores in 34 male patients treated
      with interferon alfa-2b (5 MIU three times weekly) (n=19)+ ribavirin (n=15) for 6
      12 months. Depression was measured by the Hospital Anxiety and Depression Scale.
      Sexual dysfunction was evaluated by the Symptom Checklist 90 Item Revised and a
      five-point rating scale assessing sexual arousal disorder. Free and total
      testosterone decreased significantly during antiviral therapy in close
      correlation with libido/sexual function. Depression scores increased during
      therapy and were also significantly associated with sexual dysfunction. However,
      androgen levels displayed no significant correlation with depression. These
      results suggest that interferon-induced decrease in sexual function is associated
      - but not causally related -with both androgen reduction and increased depressive
      symptoms. These findings may affect care for male hepatitis C patients during
      interferon therapy.

PMID- 15845928
TI  - The conventional wisdom and the activities of the middle range.

PMID- 15845930
TI  - Accuracy of transvaginal ultrasound in diagnosing endometrial pathology in women
      with post-menopausal bleeding on tamoxifen.
AB  - The incidence of endometrial pathology is increased in women with tamoxifen
      induced post-menopausal bleeding (PMB). The aim of this study was to determine
      the accuracy of transvaginal ultrasound (TVS) in diagnosing endometrial pathology
      in symptomatic women taking tamoxifen, using endometrial thickness measurements
      (5 mm and 10 mm cut-offs) and morphological changes within the uterine cavity to
      define abnormality. The sensitivity of TVS was 97% (95% confidence interval (CI)
      83% to 100%) and the specificity 35% (95% CI 17% to 56%) at a 5 mm threshold. The
      corresponding likelihood ratios for a positive test were 1.47 (95% CI 1.16-2.10)
      and a negative test were 0.09 (95% CI 0.02-0.53). The use of a higher 10 mm
      threshold, characterization of endometrial morphology or combining endometrial
      thickness and morphology did not improve overall accuracy. TVS measurement of
      endometrial thickness using a 5 mm cut-off is highly accurate in excluding
      endometrial disease in symptomatic women taking tamoxifen and may negate the need
      for further diagnostic testing in women unless symptoms recur. A positive TVS
      result is of little value, so further testing is mandatory in order to detect
      benign and malignant endometrial disease associated with tamoxifen and PMB.

PMID- 15845929
TI  - Stereotactic radiosurgery at St. Bartholomew's hospital: third quinquennial
      review.

PMID- 15845931
TI  - Normal radiographic anatomy of thoracic structures: analysis of 1000 chest
      radiographs in Japanese population.
AB  - The purpose of this paper was to study the frequency of visualization and
      characteristics of normal thoracic structures on posteroanterior (PA) chest
      radiographs in Japanese population. 1000 consecutive normal PA chest radiographs
      of men and women ranging in age from 20 years to 90 years were reviewed.
      Frequency of visualization and configuration of structures including (1) fissure
      lines such as major, minor, vertical fissure line, and accessory fissures, (2)
      vascular structures including normal apical opacity, aortic nipple, and
      descending aortic interface, and (3) other structures including air in the
      oesophagus, aortic pulmonary stripe, and diaphragm were studied. On PA chest
      radiographs: (1) minor fissure, superolateral major fissure, superomedial major
      fissure, vertical fissure line, superior accessory fissure, and inferior
      accessory fissure were visualized in 74.7%, 19.7%, 15.4%, 1.6%, 2.9% and 13.1%,
      respectively. (2) Normal apical opacity was seen in 3.7%, while aortic nipple was
      seen in 0.9%. Descending aortic interface was obliterated in 13.7%. (3) Air in
      the oesophagus and aortic pulmonary stripe were seen in 8.9% and 17.7%,
      respectively. Hemidiaphragm was obliterated in 10.3% on the right, and in 32.4%
      on the left. Scalloping of the diaphragm was seen in 10.6% on the right, 6.5% on
      the left, and 4.3% bilaterally. Frequency of visualization and characteristics of
      various normal anatomical structures on chest radiographs in Japanese population
      differ from those reported previously from the West. Familiarity with these
      normal thoracic structures and variations is important for our daily image
      interpretation.

PMID- 15845932
TI  - Management of non-Hodgkin's lymphoma of the thyroid: the Royal Marsden Hospital
      experience.
AB  - A retrospective review was conducted of patients treated for thyroid non
      Hodgkin's lymphoma (TNHL) at the Royal Marsden Hospital between 1936 and 1996 to
      determine the effect of radiotherapy (RT) on outcome. 91 patients were identified
      from the Thyroid Unit Database. There were 77 females and 14 males with a median
      age of 65 years (range 22-87 years). RT was delivered according to two separate
      policies: (1) involved field radiotherapy (IFRT) to the thyroid bed and cervical
      lymph nodes; (2) extended field radiotherapy (EFRT) covering the thyroid bed,
      cervical and mediastinal lymph nodes. 89 patients received RT as part of
      definitive treatment following surgery, to a dose of approximately 40 Gy. 25
      patients received IFRT and 64 patients EFRT. 27 patients received cytotoxic
      chemotherapy. 18 patients (72%) treated with IFRT died of TNHL with a median
      relapse free survival (RFS) of 10 months and a median overall survival (OS) of 21
      months. In contrast, only 29 patients (46%) treated with EFRT died of TNHL with a
      median RFS of 76 months (p = 0.01 for RFS with respect to IFRT and p = 0.04 for
      OS). Significantly more patients treated with IFRT relapsed locally (52% vs 27%).
      There was no difference in the rates of systemic relapse (20% vs 22%). EFRT alone
      for Stage I, but not for Stage II disease, yielded acceptable rates of local
      control and disease free survival with doses of at least 40 Gy. These historical
      data strongly support the addition of combination chemotherapy to the treatment
      regimen in all patients with Stage II disease. Indeed, in recent years this has
      become the standard of care for all cases of thyroid lymphoma unless the
      histology is of marginal zone type (mucosa associated lymphoma tissue (MALT)
      lymphoma).

PMID- 15845933
TI  - Transient failure of opening of the lower oesophageal sphincter on upright
      oesophagrams: radiographic and clinical findings.
AB  - The purpose of our study was to determine the frequency, radiographic features,
      and clinical importance of transient failure of opening of the lower oesophageal
      sphincter (LOS) on upright double-contrast views of the oesophagus. A
      computerized search of radiology records identified 16 patients who had transient
      failure of opening of the LOS on upright views from biphasic oesophagrams or
      upper gastrointestinal tract examinations using high-density barium but normal
      opening of the LOS on prone views using low-density barium. The radiographic
      findings were reviewed and correlated with the clinical and manometric findings.
      In all cases, barium studies revealed tapered, beaklike narrowing of the distal
      oesophagus on upright double-contrast views, with a normal-appearing distal
      oesophagus, normal opening of the LOS, and intact peristalsis on prone single
      contrast views. Only seven patients (44%) had dysphagia. Five of these patients
      had clinical follow-up, and the dysphagia improved or resolved without specific
      treatment for LOS dysfunction in four. The remaining patient had persistent
      dysphagia, but this individual had polymyositis as the likely cause for his
      dysphagia. Manometry revealed incomplete relaxation of the LOS in two patients
      and normal relaxation in one. Our experience suggests that failure of opening of
      the LOS may be observed as a transient finding of little clinical importance on
      upright double-contrast views of the oesophagus using high-density barium, with
      normal opening of the LOS on prone single-contrast views using low-density
      barium. It is important to be aware of this finding, so that it is not mistaken
      for achalasia or other abnormalities of the distal oesophagus.

PMID- 15845934
TI  - Role of ultrasound in dengue fever.
AB  - This study was performed to find out whether ultrasound is an important adjunct
      to clinical and laboratory profile in diagnosing dengue fever or dengue
      haemorrhagic fever and to further determine whether ultrasound is useful in
      predicting the severity of the disease. Ultrasound was performed on 128 patients
      (2-9 years) with clinical suspicion of dengue fever. Serological tests were
      performed to confirm the diagnosis. 40 patients were serologically negative for
      dengue fever and later excluded from the study. Of the remaining 88 serologically
      positive cases, 32 patients underwent ultrasound on second to third day, repeated
      on fifth to seventh day of fever and in 56 patients ultrasound was done only on
      fifth to seventh day of fever. Of the 32 patients who underwent the study on
      second to third day of fever, all showed gall bladder wall thickening and
      pericholecystic fluid, 21% had hepatomegaly, 6.25% had splenomegaly and right
      minimal pleural effusion. Follow-up ultrasound on fifth to seventh day revealed
      ascites in 53% left pleural effusion in 22% and pericardial effusion in 28%. Of
      the 56 patients who underwent the study on fifth to seventh day of fever for the
      first time all had gall bladder wall thickening, 21% had hepatomegaly, 7% had
      splenomegaly, 96% had ascites, 87.5% had right pleural effusion, 66% had left
      pleural effusion and 28.5% had pericardial fluid. To conclude, in an epidemic of
      dengue, ultrasound features of thickened gall bladder wall, pleural effusion and
      ascites should strongly favour the diagnosis of dengue fever.

PMID- 15845935
TI  - Colonic muco-submucosal elongated polyp: diagnosis with endoscopic ultrasound.
AB  - Colonic muco-submucosal elongated polyp is a new clinical entity first reported
      in 1998. The purpose of this report is to determine the value of endoscopic
      ultrasound in the diagnosis of this condition. We reviewed the endosonographic
      and histological findings of seven colonic muco-submucosal elongated polyps that
      were removed completely by endoscopic resection or surgery. The lesions appeared
      as pedunculated submucosal tumours, measuring 1-4 cm in maximal diameter.
      Endosonographically, all lesions consisted of mucosal and submucosal layers, and
      microcystic components were found in the submucosal layer. There were no
      echogenic masses or muscularis propria within the polyps. These endosonographic
      features corresponded to histological findings of this type of polyp which was
      covered with normal mucosa and composed of submucosal layer alone. The submucosal
      layer consisted of oedematous, loose, connective tissue and/or fibrous tissue,
      accompanied by dilated blood vessels and lymphatics. Endoscopic ultrasound
      enabled differentiation of colonic muco-submucosal elongated polyp from other
      submucosal lesions.

PMID- 15845936
TI  - Investigation of optimum energies for chest imaging using film-screen and
      computed radiography.
AB  - The purpose of the study was to compare the image quality of film-screen (FS) and
      computed radiography (CR) for adult chest examinations across a range of beam
      energies. A series of images of the CDRAD threshold contrast detail detection
      phantom were acquired for a range of tube potential and exposure levels with both
      CR and FS. The phantom was placed within 9 cm of Perspex to provide attenuation
      and realistic levels of scatter in the image. Hardcopy images of the phantom were
      scored from a masked light-box by two scorers. Threshold contrast indices were
      used to calculate a visibility index (VI). The relationships between dose and
      image quality for CR and for FS are fundamentally different. The improvements in
      VIs obtained using CR at 75 kVp and 90 kVp were found to be statistically
      significant compared with 125 kVp at matched effective dose levels. The relative
      performance of FS and CR varies as a function of energy owing to the different k
      edges of each system. When changing from FS to CR, the use of lower tube
      potentials may allow image quality to be maintained whilst reducing effective
      dose. A tube voltage of 90 kVp is indicated by this work, but may require
      clinical verification.

PMID- 15845937
TI  - A case of stunning of lung and bone metastases of papillary thyroid cancer after
      a therapeutic dose (3.7 GBq) of 131I and review of the literature: implications
      for sequential treatments.
AB  - Thyroid stunning is usually defined as the inhibition or suppression of iodide
      trapping by remnant thyroid tissue or by functioning metastases following a
      diagnostic dose of 131I. The risk of stunning increases progressively with larger
      doses. Because the threshold above which this effect occurs in thyroid remnants
      seems to be between 37 MBq and 111 MBq of 131I, therapeutic 131I doses of 3.7 GBq
      may cause stunning. We describe stunning of papillary thyroid cancer lung and
      bone metastases after a therapeutic dose of 131I (3.7 GBq). A T1 bone metastasis
      and bilateral lung metastases were diagnosed by post-therapeutic dose whole-body
      scan. Nuclear MRI detected another lesion at T4, whose 131I fixation was not
      obvious. An additional 0.7 GBq were given after recombinant TSH, 37 days after
      the therapeutic dose; 24 h later, uptake by the lung and T1 metastases had
      disappeared, but trapping was again seen 6 months later on the post-therapeutic
      scan. This re-appearance is evidence in favour of the transitory and reversible
      character of stunning, and confirms its correspondence to the decreased ability
      of viable thyroid cells to trap iodine and not to their destruction. A better
      understanding of stunning would make it possible, in the event of rapidly
      progressing disease and in conjunction with recombinant thyroid stimulating
      hormone (TSH), to give several therapeutic doses of 131I in close succession
      without each dose hampering the effectiveness of the subsequent one.

PMID- 15845938
TI  - Hepatic transit time: indicator of the therapeutic response to radiofrequency
      ablation of liver tumours.
AB  - The aim of this study was to evaluate changes of hepatic transit time (HTT) in
      patients treated by radiofrequency ablation (RFA). Five consecutive patients (2
      females, 3 males; mean age 66 years) referred for treatment of liver neoplasm
      with percutaneous application of RFA were included in this study. The HTT of
      contrast agent (Sonovue(R); Bracco International B.V., Amsterdam, The
      Netherlands) was measured in patients with liver metastases on the basis of time
      intensity curve (TIC(R)) before and after RFA, respectively. Changes of HTT
      before vs after RFA were compared with therapeutic response based on three-phase
      dynamic CT or MRI. Before RFA HTT in all 5 patients was less than 10 s (mean
      6.2+/-1.5 s). After RFA HTT in patients with complete therapeutic response was
      11.3+/-1.2 s, whereas two patients with incomplete treatment showed unchanged HTT
      below 10 s (mean 6.3+/-1.8 s). Successful RFA leads to a normalization in HTT.
      HTT using ultrasound contrast agent appears to provide a new and alternative
      approach in assessing the therapeutic effect of RFA in liver metastases.

PMID- 15845939
TI  - Case report: pulmonary blastoma: presentation of two atypical cases and review of
      the literature.
AB  - Pulmonary blastoma is a relatively rare aggressive adult malignancy. The clinical
      and radiographic features of two cases are described and the literature reviewed.
      Pulmonary blastoma usually presents radiologically as a well-defined mass lesion
      on chest radiography, which may be large enough to completely opacify the
      hemithorax and cause mediastinal shift. On CT, pulmonary blastoma is seen as a
      mixed solid and cystic lesion with variable contrast enhancement and a necrotic
      centre. Pleural effusion may be present but is not the predominant abnormality.
      Our cases are unusual as recurrent pleural effusions in the absence of a
      significant lung mass were the presenting findings.

PMID- 15845940
TI  - Case report: solid-pseudopapillary tumour of the pancreas associated with dorsal
      agenesis.
AB  - Solid-pseudopapillary tumour of the pancreas is a rare benign or low-grade
      malignant epithelial tumour; its association with pancreatic dorsal agenesis has
      been reported only once before. We present the radiological and histological
      findings of a case of pancreatic solid-pseudopapillary tumour associated with
      total pancreatic dorsal agenesis. A 49-year-old woman presented with abdominal
      pain radiating to the back for several months. Radiological findings showed
      absence of the dorsal pancreas and an 8 cm x 6 cm diameter tumour arising from
      the head of the pancreas. She underwent successful complete resection of the
      tumour. Histopathology revealed a diagnosis of solid-pseudopapillary tumour.

PMID- 15845941
TI  - Case report: myoepithelial carcinoma of the breast: a case report with imaging
      and pathological findings.
AB  - We present a case of myoepithelial carcinoma of the breast together with
      illustrations of the imaging and pathological appearances as well as discussion
      on the management of this condition.

PMID- 15845942
TI  - Case report: pericardial rupture and cardiac herniation after blunt trauma: a
      case diagnosed using cardiac MRI.
AB  - Pericardial rupture following blunt chest trauma is rare, and is not usually
      diagnosed pre-operatively. If pericardial rupture is not recognized and treated
      promptly, it may be fatal owing to cardiac herniation. We report a case of
      traumatic herniation of the heart for which a CT scan and MRI made a major
      contribution to the diagnosis.

PMID- 15845943
TI  - Case report: bilateral multilocular cystic nephromas: a rare occurrence.
AB  - We present a rare case of bilateral renal cystic tumours in an 18-month-old
      female child, which proved to be cystic nephromas on imaging and histopathology.
      Although unilateral cystic nephromas are known in children; the occurrence of
      bilateral tumours is rare.

PMID- 15845944
TI  - Case report: hepatic artery pseudoaneurysm after liver transplantation:
      definitive treatment with a stent-graft after failed coil embolisation.
AB  - A 69-year-old woman presented with massive upper gastrointestinal bleeding owing
      to a ruptured hepatic pseudoaneurysm located at the surgical arterial
      anastomosis, 2 months after combined liver and kidney transplantation. Initially
      the pseudoaneurysm was successfully coiled but 3 weeks later recurrence of her
      symptoms occurred. Hepatic angiography revealed partial reperfusion of the coiled
      pseudoaneurysm; definitive treatment was performed by placement of an expanded
      polytetrafluoroethylene (e-PTFE) covered coronary stent-graft, completely
      excluding the pseudoaneurysm. Radiological follow-up studies demonstrate a patent
      stent-graft functioning normally.

PMID- 15845945
TI  - Imaging of pelvic injuries in athletes.

PMID- 15845946
TI  - Threshold-contrast detectability curves for digital acquisition.

PMID- 15845947
TI  - Second cancer risk.

PMID- 15845949
TI  - Breast or chest? A diagnostic conundrum.

PMID- 15845950
TI  - The New York case: lessons being learned.

PMID- 15845951
TI  - Notice of retraction: final resolution.

PMID- 15845952
TI  - Notice of retraction: final resolution.

PMID- 15845953
TI  - Making decisions about mammography.

PMID- 15845954
TI  - Using pictures in the BMJ.

PMID- 15845955
TI  - New arrangements for the Medicines and Healthcare products Regulatory Agency.

PMID- 15845956
TI  - New arrangements for prison health care.

PMID- 15845957
TI  - FDA panel approves one make of silicone breast implant in the US.

PMID- 15845958
TI  - NHS care in England is still not centred on patients.

PMID- 15845959
TI  - High Court tightens conditions under which Southall may practise.

PMID- 15845960
TI  - India launches national rural health mission.

PMID- 15845963
TI  - Ruling allows EU patients to be reimbursed for treatment outside the union.

PMID- 15845964
TI  - FDA warns about using antipsychotic drugs for dementia.

PMID- 15845965
TI  - Hand washing is more important than cleaner wards in controlling MRSA.

PMID- 15845966
TI  - Dutch doctors should tackle female genital mutilation.

PMID- 15845967
TI  - Germany sets up a system for reporting medical mistakes.

PMID- 15845968
TI  - Developed world is robbing African countries of health staff.

PMID- 15845969
TI  - Research councils' requirements could bankrupt academic journals.

PMID- 15845971
TI  - Expanding the welsh NHS.

PMID- 15845972
TI  - Building a healthier Scotland.

PMID- 15845973
TI  - Patients' passports pop up again.

PMID- 15845974
TI  - Evidence based research for coping in emergencies goes online.

PMID- 15845975
TI  - Crusading for change.

PMID- 15845976
TI  - Breast reconstruction.

PMID- 15845977
TI  - In vitro and in vivo haemolysis and potassium measurement.

PMID- 15845978
TI  - Eating disorders and weight problems.

PMID- 15845979
TI  - Who needs health care--the well or the sick?

PMID- 15845980
TI  - Principles for international registration of protocol information and results
      from human trials of health related interventions: Ottawa statement (part 1).

PMID- 15845981
TI  - Why industry should register and disclose results of clinical studies-
      perspective of a recovering academic.

PMID- 15845982
TI  - Reader's guide to critical appraisal of cohort studies: 2. Assessing potential
      for confounding.

PMID- 15845983
TI  - Managing chronic diseases: care of children with chronic illness teaches some
      lessons.

PMID- 15845984
TI  - Managing chronic diseases: end of life is more than death.

PMID- 15845985
TI  - Managing chronic diseases: palliative care spectrum starts early on.

PMID- 15845987
TI  - Managing chronic diseases: combination of inhaler treatment in India has shown
      good results.

PMID- 15845988
TI  - Managing chronic diseases: condition based payment may improve care of chronic
      illness in Canada.

PMID- 15845989
TI  - Managing chronic diseases: funding follow-up is key to long term specialist care.

PMID- 15845990
TI  - Insulin resistance and depression: difference in patient groups could have been
      explained by other factors.

PMID- 15845991
TI  - Time to consider employment conditions for carers.

PMID- 15845992
TI  - Will the lead clinician please stand up? We should be promoting total quality
      care.

PMID- 15845993
TI  - Will the lead clinician please stand up? That'll be the general practitioner.

PMID- 15845994
TI  - Delayed hypersensitivity due to epidural block with ropivacaine: report raises
      several issues.

PMID- 15845996
TI  - Dynamic modulation of AMPA receptor-mediated synaptic transmission by polyamines
      in principal neurons. Focus on "polyamines modulate AMPA receptor-dependent
      synaptic response in immature layer v pyramidal neurons".

PMID- 15845997
TI  - Idling with the micro rhythm? Focus on "7 to 12 Hz activity in rat gustatory
      cortex reflects disengagement from a fluid self-administration task".

PMID- 15845995
TI  - Determinants of spatial and temporal coding by semicircular canal afferents.
AB  - The vestibular semicircular canals are internal sensors that signal the
      magnitude, direction, and temporal properties of angular head motion. Fluid
      mechanics within the 3-canal labyrinth code the direction of movement and
      integrate angular acceleration stimuli over time. Directional coding is
      accomplished by decomposition of complex angular accelerations into 3
      biomechanical components-one component exciting each of the 3 ampullary organs
      and associated afferent nerve bundles separately. For low-frequency angular
      motion stimuli, fluid displacement within each canal is proportional to angular
      acceleration. At higher frequencies, above the lower corner frequency, real-time
      integration is accomplished by viscous forces arising from the movement of fluid
      within the slender lumen of each canal. This results in angular velocity
      sensitive fluid displacements. Reflecting this, a subset of afferent fibers
      indeed report angular acceleration to the brain for low frequencies of head
      movement and report angular velocity for higher frequencies. However, a
      substantial number of afferent fibers also report angular acceleration, or a
      signal between acceleration and velocity, even at frequencies where the endolymph
      displacement is known to follow angular head velocity. These non-velocity
      sensitive afferent signals cannot be attributed to canal biomechanics alone. The
      responses of non-velocity-sensitive cells include a mathematical differentiation
      (first-order or fractional) imparted by hair-cell and/or afferent complexes. This
      mathematical differentiation from velocity to acceleration cannot be attributed
      to hair cell ionic currents, but occurs as a result of the dynamics of synaptic
      transmission between hair cells and their primary afferent fibers. The evidence
      for this conclusion is reviewed below.

PMID- 15845998
TI  - Properties of short-term synaptic depression at larval neuromuscular synapses in
      wild-type and temperature-sensitive paralytic mutants of Drosophila.
AB  - The larval neuromuscular synapse of Drosophila serves as an important model for
      genetic and molecular analysis of synaptic development and function. Further
      functional characterization of this synapse, as well as adult neuromuscular
      synapses, will greatly enhance the impact of this model system on our
      understanding of synaptic transmission. Here we describe a form of short-term
      synaptic depression observed at larval, but not adult, neuromuscular synapses and
      explore the underlying mechanisms. Larval neuromuscular synapses exhibited a form
      of short-term depression that was strongly dependent on stimulation frequency
      over a narrow range of low frequencies (0.1-1 Hz). This form of synaptic
      depression, referred to here as low-frequency short-term depression (LF-STD),
      results from an activity-dependent reduction in neurotransmitter release.
      However, in contrast to the predictions of depletion models, the degree of
      depression was independent of the initial level of neurotransmitter release over
      a range of extracellular calcium concentrations. This conclusion was confirmed in
      two temperature-sensitive (TS) paralytic mutants, cacophony and shibire, which
      exhibit reduced neurotransmitter release resulting from conditional disruption of
      presynaptic calcium channels and dynamin, respectively. Higher stimulation
      frequencies (40 or 60 Hz) produced two components of depression that appeared to
      include LF-STD as well as a more conventional component of short-term depression.
      These findings reveal novel properties of short-term synaptic depression and
      suggest that complementary genetic analysis of larval and adult neuromuscular
      synapses will further define the in vivo mechanisms of neurotransmitter release
      and short-term synaptic plasticity.

PMID- 15846000
TI  - Effects of short-term training on sensory and motor function in severed nerves of
      long-term human amputees.
AB  - Much has been studied and written about plastic changes in the CNS of humans
      triggered by events such as limb amputation. However, little is known about the
      extent to which the original pathways retain residual function after peripheral
      amputation. Our earlier, acute study on long-term amputees indicated that central
      pathways associated with amputated peripheral nerves retain at least some sensory
      and motor function. The purpose of the present study was to determine if these
      functional connections would be strengthened or improved with experience and
      training over several days time. To do this, electrodes were implanted within
      fascicles of severed nerves of long-term human amputees to evaluate the changes
      in electrically evoked sensations and volitional motor neuron activity associated
      with attempted phantom limb movements. Nerve stimulation consistently resulted in
      discrete, unitary, graded sensations of touch/pressure and joint-position sense.
      There was no significant change in the values of stimulation parameters required
      to produce these sensations over time. Similarly, while the amputees were able to
      improve volitional control of motor neuron activity, the rate and pattern of
      change was similar to that seen with practice in normal individuals on motor
      tasks. We conclude that the central plasticity seen after amputation is most
      likely primarily due to unmasking, rather than replacement, of existing synaptic
      connections. These results also have implications for neural control of
      prosthetic limbs.

PMID- 15845999
TI  - Response characterstics of spinothalamic tract neurons that project to the
      posterior thalamus in rats.
AB  - A sizeable number of spinothalamic tract axons terminate in the posterior
      thalamus. The functional roles and precise areas of termination of these axons
      have been a subject of recent controversy. The goals of this study were to
      identify spinothalamic tract neurons (STT) within the cervical enlargement that
      project to this area, characterize their responses to mechanical and thermal
      stimulation of their receptive fields, and use microantidromic tracking methods
      to determine the nuclei in which their axons terminate. Forty-seven neurons were
      antidromically activated using low-amplitude (< or =30 microA) current pulses in
      the contralateral posterior thalamus. The 51 points at which antidromic
      activation thresholds were lowest were surrounded by ineffective tracks
      indicating that the surrounded axons terminated within the posterior thalamus.
      The areas of termination were located primarily in the posterior triangular,
      medial geniculate, posterior and posterior intralaminar, and suprageniculate
      nuclei. Recording points were located in the superficial and deep dorsal horn.
      The mean antidromic conduction velocity was 6.4 m/s, a conduction velocity slower
      than that of other projections to the thalamus or hypothalamus in rats. Cutaneous
      receptive fields appeared to be smaller than those of neurons projecting to other
      areas of the thalamus or to the hypothalamus. Each of the examined neurons
      responded exclusively or preferentially to noxious stimuli. These findings
      indicate that the STT carries nociceptive information to several target nuclei
      within the posterior thalamus. We discuss the evidence that this projection
      provides nociceptive information that plays an important role in fear
      conditioning.

PMID- 15846001
TI  - Temporal representation of the delay of iterated rippled noise in the dorsal
      cochlear nucleus.
AB  - It has been suggested that the dorsal cochlear nucleus (DCN) is involved in the
      temporal representation of both envelope periodicity and pitch. This hypothesis
      is tested using iterated rippled noise (IRN), which is generated by a cascade of
      delay and add [IRN(+)] or delay and subtract [IRN(-)] operations. The
      autocorrelation functions (ACFs) of the waveform and the envelope of IRN(+) have
      a first peak at the delay, which corresponds to the perceived pitch of the IRN.
      With the same delay, the pitch of IRN(-) is generally an octave lower than for
      IRN(+). This is reflected in a first peak at twice the delay in the ACF of the
      waveform for IRN(-). In contrast, for identical delays, the ACF of the envelope
      for both IRN(-) and IRN(+) is the same. Thus the use of IRN allows the
      distinction between envelope- or fine-structure sensitivity. Recordings were made
      from 135 single units (BFs <5 kHz) in the DCN of the anesthetized guinea pig
      using IRN with delays ranging from 1 to 32 ms. In our sample 42% were sensitive
      to the periodicity of IRN(+) and were tuned to a particular delay in their first
      order interspike interval histograms (ISIHs). This tuning was highly correlated
      with their response to white noise. Most units with best frequencies (BFs) <500
      Hz show a different all-order ISIH for IRN(+) and IRN(-), which corresponds to
      the perceived pitch difference, whereas units with higher BFs show a similar
      response to IRN(+) and IRN(-). The results indicate that low-frequency units (BF
      <500 Hz) in the DCN may be involved in the representation of the waveform fine
      structure, although units with BFs >500 Hz are able to encode only the envelope
      periodicity of broadband IRN in their temporal discharge characteristics.

PMID- 15846002
TI  - Fimbria-fornix lesions compromise the induction of long-term potentiation at the
      Schaffer collateral-CA1 synapse in the rat in vivo.
AB  - Although bilateral fimbria-fornix (FF) lesioning impairs spatial performance in
      animals, the literature is equivocal regarding its effects on hippocampal long
      term potentiation (LTP). We examined the effects of FF lesioning on LTP induction
      in the Schaffer collateral-CA1 pathway in vivo with a protocol that delivered
      theta burst stimulation (TBS) trains of increasing length until a sufficient
      length was reached to induce LTP of the monosynaptic field excitatory
      postsynaptic potential (fEPSP). Experiments were performed in urethan
      anesthetized Long-Evans rats either 4 or 12-16 wk after lesioning. In sham
      operated controls, TBS trains ranging from 4 to 12 bursts were sufficient to
      induce robust LTP [170 +/- 10% (mean +/- SF) of control fEPSP slope; n = 8]. Four
      week post -FF-lesioned animals also displayed clear LTP (167 +/- 12% of control
      fEPSP slope; n = 4) that did not differ from the shams (P > 0.05). In contrast,
      animals in the 12- to 16-wk post-lesion group showed a highly significant deficit
      in LTP induction (95 +/- 3% of control fEPSP slope; n = 8; < or =28 burst TBS
      trains tested; P < 0.001 vs. sham- and 4-wk post-FF-lesion groups). Other
      quantitative measures of synaptic excitability (i.e., baseline fEPSP slope and
      input-output relation) did not differ between the sham- and the 12- to 16-wk post
      FF-lesion groups. These results indicate that the FF lesion leads to an enduring
      defect in hippocampal long-term synaptic plasticity that may relate
      mechanistically to the cognitive deficits characterized in this model.

PMID- 15846003
TI  - Managing the baby with a patent ductus arteriosus. More questions than answers?

PMID- 15846004
TI  - Participation in multiple neonatal research studies.

PMID- 15846005
TI  - Standardised feeding regimens: hope for reducing the risk of necrotising
      enterocolitis.

PMID- 15846006
TI  - Prevalence, causes, and outcome at 2 years of age of newborn encephalopathy.

PMID- 15846007
TI  - Quality of care by neonatal nurse practitioners: a review of the Ashington
      experiment.
AB  - The Ashington experiment, an innovative neonatal service run entirely by advanced
      neonatal nurse practitioners (ANNPs), has been evaluated. This is a report of
      that evaluation and a review of the benefits, hazards, and implications of nurse
      practitioner led services.

PMID- 15846008
TI  - Role of cerebral function monitoring in the newborn.
AB  - For many years, newborn infants admitted to neonatal intensive care units have
      had routine electrocardiography and been monitored for respiratory rate, heart
      rate, oxygen saturation, and blood pressure. Only recently has it also been
      considered important to monitor brain function using continuous
      electroencephalography. The role of cerebral function monitoring in sick full
      term and preterm infants is reviewed.

PMID- 15846009
TI  - Resuscitation of the preterm infant against parental wishes.
AB  - Over the past 40 years, the norms on who is to make treatment decisions for
      newborns, and on what standards, have been significantly altered and revised.
      Today the standard for treatment of newborns is the "best interest" of the child.
      A recent ruling of the Texas Supreme Court authorizing a doctor to resuscitate a
      potentially viable very premature newborn over the parents' objection is a
      challenge to that standard.

PMID- 15846010
TI  - Neonatal pneumonia in developing countries.
AB  - Pneumonia contributes to between 750,000 and 1.2 million neonatal deaths and an
      unknown number of stillbirths each year world wide. The aetiology depends on time
      of onset. Gram negative bacilli predominate in the first week of life, and Gram
      positive bacteria after that. Streptococcus pneumoniae probably causes about 25%
      of neonatal pneumonia. Interventions that would reduce mortality from this
      condition would have a large range of beneficial effects: improved maternal
      health, better management of other common neonatal conditions, and reduced long
      term childhood and adult morbidity.

PMID- 15846011
TI  - Neonatal sepsis: an international perspective.
AB  - Neonatal infections currently cause about 1.6 million deaths annually in
      developing countries. Sepsis and meningitis are responsible for most of these
      deaths. Resistance to commonly used antibiotics is emerging and constitutes an
      important problem world wide. To reduce global neonatal mortality, strategies of
      proven efficacy, such as hand washing, barrier nursing, restriction of antibiotic
      use, and rationalisation of admission to neonatal units, need to be implemented.
      Different approaches require further research.

PMID- 15846012
TI  - What do parents think about enrolling their premature babies in several research
      studies?
AB  - OBJECTIVE: To investigate parents' opinions about enrolling their premature baby
      into several research studies in the few days after birth. METHODOLOGY: A
      questionnaire was given to parents of premature babies in the neonatal intensive
      care unit who had been invited to join several studies (two to seven). RESULTS:
      All 50 mothers and 42 of 48 fathers completed the questionnaire independently;
      28% had been asked to join two studies, 32% three, 24% four, 14% five, and 2% six
      studies. There were 61 babies with mean (SD) gestational age 26.9 (1.6) weeks and
      birth weight 877 (249) g. Nearly three quarters (71%) of the parents thought it
      was very good for their baby to be in a hospital that was carrying out a lot of
      research. Most (93%) thought that their baby would get the same or better care in
      a study. Only 15% thought their baby was too small for research studies. Almost
      all (98%) wanted to be involved in the decision about their baby joining a study.
      Only 22% were worried about the number of studies; 10% would not enroll their
      baby in any studies, but 74% were willing for their baby to join two or more
      studies, and 10% would enroll in all the studies. Most (94%) believed that their
      baby's participation would improve care of future babies. CONCLUSIONS: Most of
      these parents were willing to join several studies. The majority were not worried
      about their baby participating in the studies. The profession needs to be aware
      that parents are supportive of neonatal research and participation in multiple
      studies.

PMID- 15846013
TI  - Restoration of cardiopulmonary function with 21% versus 100% oxygen after
      hypoxaemia in newborn pigs.
AB  - OBJECTIVE: To assess the consequences of hypoxaemia and resuscitation with room
      air versus 100% O(2) on cardiac troponin I (cTnI), cardiac output (CO), and
      pulmonary artery pressure (PAP) in newborn pigs. DESIGN: Twenty anaesthetised
      pigs (12-36 hours; 1.7-2.7 kg) were subjected to hypoxaemia by ventilation with
      8% O(2). When mean arterial blood pressure fell to 15 mm Hg, or arterial base
      excess was < or = -20 mmol/l, resuscitation was performed with 21% (n = 10) or
      100% (n = 10) O(2) for 30 minutes, then ventilation with 21% O(2) for 120
      minutes. Blood was analysed for cTnI. Ultrasound examinations of CO and PAP
      (estimated from tricuspid regurgitation velocity (TR-Vmax)) were performed at
      baseline, during hypoxia, and at the start of and during reoxygenation. RESULTS:
      cTnI increased from baseline to the end point (p<0.001), confirming a serious
      myocardial injury, with no differences between the 21% and 100% O(2) group (p =
      0.12). TR-Vmax increased during the insult and returned towards baseline values
      during reoxygenation, with no differences between the groups (p = 0.11) or
      between cTnI concentrations (p = 0.31). An inverse relation was found between
      increasing age and TR-Vmax during hypoxaemia (p = 0.034). CO per kg body weight
      increased during the early phase of hypoxaemia (p<0.001), then decreased. Changes
      in CO per kg were mainly due to changes in heart rate, with no differences
      between the groups during reoxygenation (p = 0.298). CONCLUSION: Hypoxaemia
      affects the myocardium and PAP. During this limited period of observation,
      reoxygenation with 100% O(2) showed no benefits compared with 21% O(2) in
      normalising myocardial function and PAP. The important issue may be resuscitation
      and reoxygenation without hyperoxygenation.

PMID- 15846014
TI  - Simple management of isolated proptosis at birth.

PMID- 15846015
TI  - Is surgical ligation of patent ductus arteriosus necessary? The Western
      Australian experience of conservative management.
AB  - BACKGROUND: Surgical ligation of patent ductus arteriosus (PDA) is widely
      practised in preterm infants despite no clear evidence that this improves
      outcomes. Geographical isolation meant that ductal ligation was not an option in
      King Edward Memorial Hospital until recently. OBJECTIVE: A retrospective data
      analysis to test the hypothesis that outcomes of infants with persistent PDA were
      no worse than those of infants with no significant duct or a duct that closed
      after medical treatment. PATIENTS AND METHODS: A total of 252 infants (gestation
      < or =28 weeks) born between 1 January 2000 and 30 June 2002 were divided into
      three groups: group 1, no significant PDA (n = 154); group 2, significant PDA
      which closed after medical treatment (n = 65); group 3, significant PDA remaining
      patent after medical treatment (n = 33). A significant PDA was defined by a left
      atrium to aortic root ratio of >1.4 or a ductal diameter >1.5 mm with a left to
      right shunt. RESULTS: Twenty four (10%) infants died at median (interquartile
      range) 15.5 (9-35) days. After adjustment for gestational age, relative to group
      1, the infants from group 3 were at a 4.02 times increased risk of death (95%
      confidence interval 1.12 to 14.51). There was no significant difference between
      groups in the incidence of chronic lung disease, chronic lung disease or death,
      necrotising enterocolitis, intraventricular haemorrhage, duration of oxygen, or
      hospital stay. CONCLUSION: Mortality was higher in infants with a persistent PDA,
      but other morbidities were not significantly different. A randomised trial is
      needed to determine whether surgical ligation will reduce mortality in such
      infants.

PMID- 15846016
TI  - UK population based study of severe retinopathy of prematurity: screening,
      treatment, and outcome.
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is one of the few causes of
      childhood blindness in which severe vision impairment is largely preventable.
      Ophthalmic screening for ROP is required to identify disease that requires
      treatment whereby the development of potentially blinding disease can be
      minimised. OBJECTIVES: To make the first UK population based estimate of the
      incidence of babies with severe ROP (stage 3 or more); to document their clinical
      characteristics and management and to evaluate the appropriateness of current ROP
      screening guidelines in the UK. PATIENTS: Cases were recruited through a national
      surveillance programme with 1 year ophthalmic follow up and data from clinician
      completed questionnaires. RESULTS: Between 1 December 1997 and 31 March 1999, 233
      preterm babies with stage 3 ROP were identified. Severity (location, extent, and
      presence of plus disease) was associated with degree of prematurity, most severe
      in the most premature babies. Fifty nine percent were treated. The UK screening
      protocol was followed in two thirds of cases, but in the remainder it was begun
      too late or was too infrequent. Three quarters of the cases were followed up at 1
      year, and 13% had a severe vision deficit as a result of ROP. CONCLUSIONS: Visual
      deficit as a result of ROP in premature babies continues to be a severe
      disability in some of the survivors of neonatal intensive care. Further efforts
      are needed to organise treatment regionally to improve outcome and standards of
      practice.

PMID- 15846017
TI  - Recovery of amplitude integrated electroencephalographic background patterns
      within 24 hours of perinatal asphyxia.
AB  - OBJECTIVE: To assess the time course of recovery of severely abnormal initial
      amplitude integrated electroencephalographic (aEEG) patterns (flat trace (FT),
      continuous low voltage (CLV), or burst suppression (BS)) in full term asphyxiated
      neonates, in relation to other neurophysiological and neuroimaging findings and
      neurodevelopmental outcome. METHODS: A total of 190 aEEGs of full term infants
      were reviewed. The neonates were admitted within 6 hours of birth to the neonatal
      intensive care unit because of perinatal asphyxia, and aEEG recording was started
      immediately. In all, 160 infants were included; 65 of these had an initial FT or
      CLV pattern and 25 an initial BS pattern. Neurodevelopmental outcome was assessed
      using a full neurological examination and the Griffiths' mental developmental
      scale. RESULTS: In the FT/CLV group, the background pattern recovered to
      continuous normal voltage within 24 hours in six of the 65 infants (9%). All six
      infants survived the neonatal period; one had a severe disability, and five were
      normal at follow up. In the BS group, the background pattern improved to normal
      voltage in 12 of the 25 infants (48%) within 24 hours. Of these infants, one
      died, five survived with moderate to severe disability, two with mild disability,
      and four were normal. The patients who did not recover within 24 hours either
      died in the neonatal period or survived with a severe disability. CONCLUSION: In
      this study there was a small group of infants who presented with a severely
      abnormal aEEG background pattern within six hours of birth, but who achieved
      recovery to a continuous normal background pattern within the first 24 hours.
      Sixty one percent of these infants survived without, or with a mild, disability.

PMID- 15846018
TI  - Does cranial ultrasound imaging identify arterial cerebral infarction in term
      neonates?
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of cranial ultrasound (CUS) for
      detection of neonatal arterial territory cerebral infarction in term infants.
      METHODS: CUS scans from term infants with neonatal magnetic resonance imaging
      (MRI) evidence of neonatal infarction were reviewed. The scans were grouped by
      acquisition time after birth: 1-3 days (early) or 4-14 days (late). RESULTS:
      Brain MRI showed infarction in the territory of the middle cerebral artery in 43
      of 47 infants, anterior cerebral artery in one, and posterior cerebral artery in
      three. Twelve of the 47 had minor changes on MRI in the white matter in the
      contralateral hemisphere, and four infants had bilateral infarctions. The early
      CUS scans were abnormal in 68% of the infants; the late CUS scans were abnormal
      in 87%. The late CUS scans were correct for laterality and site of lesion in
      25/47 (53%) infants. In six infants with smaller lesions of the cortical middle
      cerebral artery branch or lesions in the posterior cerebral artery territory, the
      CUS scans were persistently normal. CONCLUSION: Normal early CUS scans do not
      exclude a diagnosis of neonatal stroke, although most scans are abnormal. CUS
      scans performed after day 3 were abnormal in 87% of infants. CUS scan findings
      were accurate for lesion laterality and site in 53%, and, in 34%, the scans
      showed abnormality strongly suggestive of infarction but not always site
      specific. For optimal prognostic information, infants with clinical histories or
      CUS scan findings suggestive of infarction should have a neonatal brain MRI scan.

PMID- 15846019
TI  - Prevalence, causes, and outcome at 2 years of age of newborn encephalopathy:
      population based study.
AB  - OBJECTIVES: To ascertain the prevalence of newborn encephalopathy in term live
      births, and also the underlying diagnoses, timing, and outcome at 2 years of
      surviving infants. DESIGN: Population based observational study. SETTING: North
      Pas-de-Calais area of France, January to December 2000. PATIENTS: All 90 neonates
      with moderate or severe newborn encephalopathy. RESULTS: The prevalence of
      moderate or severe newborn encephalopathy was 1.64 per 1000 term live births (95%
      confidence interval (CI) 1.30 to 1.98). The prevalence of birth asphyxia was 0.86
      per 1000 term live births (95% CI 0.61 to 1.10). The main cause of newborn
      encephalopathy was birth asphyxia, diagnosed in 47 (52%) infants. It was
      associated with another diagnosis in 11/47 cases (23%). The timing was
      intrapartum in 56% of cases, antepartum in 13%, ante-intrapartum in 10%, and
      postpartum in 2%. In 19% of cases, no underlying cause was identified during the
      neonatal course. Twenty four infants died in the neonatal period, giving a
      fatality rate of 27% (95% CI 17% to 36%). Three infants died after the neonatal
      period. At 2 years of age, 38 infants had a poor outcome, defined by death or
      severe disability, a prevalence of 0.69 per 1000 term live births (95% CI 0.47 to
      0.91). In infants with isolated birth asphyxia, this prevalence was 0.36 per 1000
      term live births (95% CI 0.20 to 0.52). CONCLUSIONS: The causes of newborn
      encephalopathy were heterogeneous but the main one was birth asphyxia. The
      prevalence was low, but the outcome was poor, emphasising the need for prevention
      programmes and new therapeutic approaches.

PMID- 15846020
TI  - Significant head cooling can be achieved while maintaining normothermia in the
      newborn piglet.
AB  - BACKGROUND: Hypothermia has been shown to be neuroprotective in animal models of
      hypoxia-ischaemia. It is currently being evaluated as a potentially therapeutic
      option in the management of neonatal hypoxic-ischaemic encephalopathy. However,
      significant hypothermia has adverse systemic effects. It has also recently been
      found that the stress of being cold can abolish the neuroprotective effects of
      hypothermia. It is hypothesised that selective head cooling (SHC) while
      maintaining normal core temperature would enable local hypothermic
      neuroprotection while limiting the stress and side effects of hypothermia.
      OBJECTIVE: To determine whether it is possible to induce moderate cerebral
      hypothermia in the deep brain of the piglet while maintaining the body at
      normothermia (39 degrees C). METHODS: Six piglets (<48 hours old) were
      anaesthetised, and temperature probes inserted into the brain. Temperature was
      measured at different depths from the brain surface (21 mm (T(deep brain)) to 7
      mm (T(superficial brain))). After a 45 minute global hypoxic-ischaemic insult,
      each piglet was head cooled for seven hours using a cap circulated with cold
      water (median 8.9 degrees C (interquartile range 7.5-14)) wrapped around the
      head. Radiant overhead heating was used to warm the body during cooling. RESULTS:
      During SHC it was possible to cool the brain while maintaining a normal core
      temperature. The mean (SD) T(deep brain) during the seven hour cooling period was
      31.1 (4.9) degrees C while T(rectal) remained stable at 38.8 (0.4) degrees C. The
      mean T(rectal)-T(deep brain) difference throughout the cooling period was 9.8
      (6.1) degrees C. The mean T(skin) required was 40.8 (1.1) degrees C. There was no
      evidence of skin damage secondary to these skin temperatures. During cooling only
      one piglet shivered. CONCLUSIONS: It is possible to maintain systemic
      normothermia in piglets while significantly cooling the deeper structures of the
      brain. This method of cooling may further limit the side effects associated with
      systemic hypothermia and be feasible for premature infants.

PMID- 15846022
TI  - Autopsy after death due to extreme prematurity.
AB  - Autopsy reports for 29 very preterm infants dying at <28 days of age were
      reviewed. New findings were discovered in 79% and resulted in a significant
      change in diagnoses in 28%. Iatrogenic lesions were identified in 41% of cases
      and were the main cause of death in 14%.

PMID- 15846021
TI  - What factors are important to parents making decisions about neonatal research?
AB  - BACKGROUND: Although parents of neonates with congenital heart disease are often
      asked permission for their neonates to participate in research studies, little is
      known about the factors parents consider when making these decisions. OBJECTIVE:
      To determine the reasons for parents' decisions about participation in research
      studies. METHODS: Qualitative analysis of the unsolicited comments of 34 parents
      regarding reasons for agreeing or declining to participate in research studies.
      Parents' comments were offered spontaneously during interviews about clinical
      care decisions for neonates with congenital heart disease. RESULTS: Parents cited
      five types of reason for or against permitting their newborn to participate in
      research studies: societal benefit (n = 18), individual benefit for their infant
      (n = 16), risk of study participation (n = 10), perception that participation
      posed no harm (n = 9), and anti-experimentation views (n = 4). CONCLUSION:
      Addressing parental decision making in the light of these reasons could enhance
      the parental permission process for parents of critically ill neonates.

PMID- 15846023
TI  - Skinfold measurements at birth: sex and anthropometric influence.
AB  - Weight, length, and skinfold thicknesses were measured in 4634 term and preterm
      neonates. Sex and weight/length ratio were important determinants of the amount
      and distribution of the subcutaneous fat store at birth. Gestational age, weight,
      length, and other ponderal indices did not explain subcutaneous fat variability.

PMID- 15846024
TI  - Prenatal exposure to arecoline (areca nut alkaloid) and birth outcomes.
AB  - The betel nut is commonly used as a drug by Asian populations. A high prevalence
      of adverse pregnancy outcomes has been reported in women who chewed betel quid
      during gestation. The hypothesis that chronic exposure of the fetus to arecoline
      (the principal alkaloid of the areca nut) is the cause was investigated in a
      clinical observational study on six newborns from Asian mothers who chewed betel
      nut during pregnancy.

PMID- 15846025
TI  - Sir George Newman, MD (1870-1948) and the prevention of perinatal disease.
AB  - At the start of the 20th century, 15% of all infants in England and Wales died in
      the first year of life. Newman's classic work Infant mortality, published in
      1906, identified the causes of these deaths, the significance of the period
      immediately after birth, the social problems underlying mortality, and possible
      methods of prevention. Later, as chief medical officer to the Board of Education
      (1907-1935) and to the Ministry of Health (1919-1935), he achieved many important
      and wide ranging improvements to the health of infants and children.

PMID- 15846026
TI  - Nutritional infantile vitamin B12 deficiency: pathobiochemical considerations in
      seven patients.

PMID- 15846027
TI  - Specific alteration of the Bax/Bcl2 ratio and cytochrome c without execution of
      apoptosis in the hippocampus of aged baboons.
AB  - PURPOSE: During ageing, there may be an age-associated loss of particular nerve
      cells in specific brain areas. Recent studies highlight the role of apoptosis in
      the normal ageing of the brain, heart, and skeletal muscle. Particular attention
      is paid to the role of cytochrome c release from mitochondria and alterations in
      the pro- and anti-apoptotic proteins, Bax and Bcl-2, respectively. The aim of
      this study was to investigate the potential occurrence of apoptosis in the
      hippocampus of aged baboons. METHODS: we have used the baboon as a potential non
      human primate model for age-related pathology which afflicts the human brain. The
      TUNEL staining method was used to characterise the apoptotic cell death. For
      immunocytochemistry, antibodies directed against activated caspase-3, cytochrome
      c, Bcl-2 and Bax proteins were used. RESULTS: Our results show that in hippocampi
      of aged baboons the immunoreactivities of the antiapoptotic agent Bcl-2 was not
      prominently changed, of the proapoptotic agent Bax was upregulated, of the
      cytochrome c was redistributed, and that caspase-3 was not activated. The TUNEL
      staining method revealed no apoptotic cell death in hippocampi of aged baboons.
      CONCLUSIONS: This demonstrates that a specific alteration of the Bax/Bcl2 ratio
      occurs in the ageing baboon hippocampus which may directly influence the release
      of cytochrome c even without commitment to apoptosis.

PMID- 15846028
TI  - Diffusion anisotrophy in the early stages of stroke can predict motor outcome.
AB  - PURPOSE: This study examined whether the degree of impairment of diffusion
      anisotrophy in the early stages of a stroke can predict the motor function
      outcome. METHODS: Thirty-one hemiplegic stroke patients were enrolled to this
      study. Diffusion anisotropy was measured by determining fractional anisotropy
      (FA) in the two ROIs (region of interests) at corona radiata (CR) and in the
      posterior limb of internal capsule (IC) during the early stages of stoke (average
      7.9 days after stroke onset) and compared with motor outcome of the affected hand
      3 months after stroke onset. RESULTS: Both ROIs (CR or IC) and lesion types
      (hemorrhage or infarction) did not have significant effect on the SBFA (symmetry
      of bilateral FA) and dMRC (medical research council score improvement), either.
      Patients with greater initial MRC score had significantly greater SBFA and dMRC.
      The regression equation between the dMRC (Y axis) and the SBFA (X axis) was semi
      linear and significant (P < 0.05); for CR group, Y = 3.296 - 0.1192X + 0.0015X2;
      for IC group, Y = 2.342 - 0.0533X +0.0007(2). The regression lines had 'threshold
      points' where a minute SBFA change would make a steep increase in dMRC.
      CONCLUSION: The degree of impairment in diffusion anisotropy during the early
      stages of stroke appears to have the potential to predict motor outcome.

PMID- 15846029
TI  - Peripheral nerve regeneration through a synthetic hydrogel nerve tube.
AB  - PURPOSE: As alternatives to nerve grafts for peripheral nerve repair, we have
      synthesized 12 mm long poly(2-hydroxyethyl methacrylate-co-methyl methacrylate)
      (PHEMA-MMA) porous tubes and studied their regenerative capacity for the repair
      of surgically-created 10 mm rat sciatic nerve gaps. We compared the in vivo
      regenerative efficacy of these artificial tubes with the gold standard, the nerve
      autograft. METHODS: Tubes were assessed in vivo for their ability to support
      nerve regeneration at 4, 8, and 16 weeks post-implantation by histology,
      electrophysiology, histomorphometry, and reinnervated lateral gastrocnemius (LG)
      dry muscle mass. RESULTS: Axonal regeneration within the tubes was observed by 8
      weeks, with outcome parameters comparable to autografts. This finding was further
      supported by the electrophysiological and histomorphometric results. The 16 week
      tube group had a bimodal response, with 60% of the tubes having a similar
      response to autografts and the other 40% having significantly lower (p < 0.05)
      outcome measures in several parameters. CONCLUSIONS: Axonal regeneration in
      artificial tubes was similar to that in autografts at 8 and 16 weeks, however, a
      bimodal distribution of regeneration was observed in 16 week tubes.

PMID- 15846030
TI  - Administration of monoclonal antibodies neutralizing the inflammatory mediators
      tumor necrosis factor alpha and interleukin -6 does not attenuate acute
      behavioral deficits following experimental traumatic brain injury in the rat.
AB  - PURPOSE: Although many previous studies have indicated that the acute
      inflammatory response following traumatic brain injury (TBI) is detrimental,
      inflammation may also positively influence outcome in the more chronic post
      injury recovery period. We evaluated the effects of monoclonal antibodies (mAB),
      neutralizing either IL-6 (IL-6 mAB) or TNF-alpha (TNF mAB), administered
      intracerebroventricularly (i.c.v) on acute neurobehavioral outcome following TBI.
      METHODS: Male Sprague-Dawley rats (n = 173) were anesthetized (sodium
      pentobarbital, 60 mg/kg) and subjected to lateral fluid percussion (FP) brain
      injury of moderate severity (n = 123) or sham injury (n = 50). Beginning 1 h post
      injury, TNF mAB (n = 41, of which 25 were brain-injured) or IL-6 mAB (n = 42, of
      which 25 were brain-injured) at a concentration of 2 mg/mL was infused i.c.v
      ipsilateral to the injury for 48 hours. Vehicle-treated animals (control IgG; n =
      43, of which 26 were brain-injured) served as controls. In Study 1, cognitive
      function was evaluated in the Morris Water Maze (MWM) followed by evaluation of
      regional cerebral edema at 48 h post-injury. In Study 2, animals were evaluated
      for neurological motor function and post-injury learning in the MWM at one week
      post-injury. RESULTS: FP brain injury caused significant cognitive (p < 0.05) and
      neurological motor (p < 0.05) deficits and increased regional brain water content
      in the injured hemisphere. Treatment with either TNF- or IL-6-mAB had no effect
      on neurological motor, cognitive function or brain edema during the first post
      injury week. CONCLUSIONS: Evaluation of anti-inflammatory mABs on more chronic
      behavioral deficits appears warranted.

PMID- 15846031
TI  - Post-training stimulation of the basolateral amygdala improves spatial learning
      in rats with lesion of the fimbria-fornix.
AB  - PURPOSE: To evaluate the capacity of amygdala stimulation to improve neural
      plasticity in animals bearing lesions of the fimbria-fornix (FF) system. METHODS:
      The animals were lesioned under narcosis (chloral hydrate, 420 mg/kg ip.) using a
      bilateral transection of the FF procedure. During the same surgery some animals
      were implanted with an electrode in the right basolateral amygdala (BLA) to allow
      the electrical stimulation of this structure. Training was carried out one week
      after surgery using a Morris water maze. Animals were trained in four consecutive
      days (8 trials/day) in the non-visible platform condition except in the fourth
      day in which only 4 trials were performed followed by a probe trial in which the
      escape platform was removed. On day 5 of training 8 trials with visible platform
      were performed. After each of the first 3 training days one group of animals
      received trains of electrical stimulation to the BLA, while control groups were
      not stimulated. A group of non-lesioned animals served as control. The location
      of the electrode was confirmed histologically after the end of the experiments.
      RESULTS: The learning capacity of the lesioned animals was improved by the
      electrical stimulation of the amygdala. The latency to find the submerged
      platform within this group approaches that of the non lesioned animals in the
      course of training (2-way ANOVA with repeated measures), while other lesioned
      animals continued to show severely impaired learning abilities. CONCLUSIONS: This
      is the first evidence that stimulating the BLA can positively influence the
      learning abilities of lesioned animals. Further experiments should contribute to
      improve the stimulation paradigms to make it more effective, if possible.

PMID- 15846032
TI  - Motor recovery mechanism of diffuse axonal injury: a combined study of
      transcranial magnetic stimulation and functional MRI.
AB  - PURPOSE: The purpose of this study was to investigate the motor recovery
      mechanism following diffuse axonal injury (DAI) using transcranial magnetic
      stimulation (TMS) and functional MRI (fMRI). METHODS: Twenty-six hands of 13
      control subjects and 14 affected hands of 8 patients (two hemiparetics and six
      quadriparetics) were evaluated. All the patients were initially diagnosed with
      DAI and were evaluated after they had reached their maximal motor recovery. fMRI
      was performed at 1.5 T using a hand grasp-release movement paradigm and TMS was
      applied with a round coil over the vertex. RESULTS: fMRI revealed that both
      normal subjects and patients with DAI showed increased contralateral primary
      sensori-motor cortex activation during affected hand movement. The motor evoked
      potentials (MEPs) of the patient group was slightly delayed in latency and
      significantly increased in duration and turns. The relative MEP amplitude, phase,
      and excitatory threshold were not significantly different between the groups.
      CONCLUSIONS: These findings may indicate the heterogeneity of the axons in the
      recovery process of the corticospinal tract. It seems that the motor recovery in
      patients who had suffered DAI was attributable to the recovery of the
      corticospinal tract.

PMID- 15846033
TI  - Absolute measurement of lattice parameter in single crystals and epitaxic layers
      on a double-crystal X-ray diffractometer.
AB  - Details of the recently developed 'zone technique' for the absolute measurement
      of lattice parameter and strain in single-crystal solids and thin films are
      presented. The method is based on measuring X-ray rocking curves from a few
      equatorial planes within a suitable zone and correcting their peak positions at
      once with a single zero offset. In contrast to the comparative method, which
      usually requires use of two opposite azimuthal directions, those in the zone
      technique can often be completed in only one azimuthal setting. A typical
      strained layer in the cubic system can be fully and rapidly characterized with
      only three rocking curves. The technique is suitable for routine applications
      under typical laboratory conditions, and for high-precision measurements of
      nearly perfect crystals in a controlled environment, with a potential parts in 10
      million accuracy. This degree of accuracy is a direct consequence of the zero
      offset correction procedure, which effectively cancels a large portion of the
      misalignment errors in the diffractometer. The use of the (n, -n) geometry
      substantially reduces the errors of eccentricity compared to the Bond technique,
      and its stronger reflections enable the measurement of small samples about 0.05
      mm in length with relative ease. The technique is illustrated with examples, and
      its extension to the triple-axis (omega-2theta) instruments is discussed.

PMID- 15846034
TI  - The invariom model and its application: refinement of D,L-serine at different
      temperatures and resolution.
AB  - Three X-ray data sets of the same D,L-serine crystal were measured at
      temperatures of 298, 100 and 20 K. These data were then evaluated using invarioms
      and the Hansen & Coppens aspherical-atom model. Multipole populations for
      invarioms, which are pseudoatoms that remain approximately invariant in an
      intermolecular transfer, were theoretically predicted using different density
      functional theorem (DFT) basis sets. The invariom parameters were kept fixed and
      positional and thermal parameters were refined to compare the fitting against the
      multi-temperature data at different resolutions. The deconvolution of thermal
      motion and electron density with respect to data resolution was studied by
      application of the Hirshfeld test. Above a resolution of sin theta/lambda
      approximately 0.55 A-1, or d approximately 0.9 A, this test was fulfilled. When
      the Hirshfeld test is fulfilled, a successful modeling of the aspherical electron
      density with invarioms is achieved, which was proven by Fourier methods.
      Molecular geometry improves, especially for H atoms, when using the invariom
      method compared to the independent-atom model, as a comparison with neutron data
      shows. Based on this example, the general applicability of the invariom concept
      to organic molecules is proven and the aspherical density modeling of a larger
      biomacromolecule is within reach.

PMID- 15846035
TI  - Astigmatic electron diffraction imaging: a novel mode for structure
      determination.
AB  - In a conventional transmission electron microscope, stigmators are used to
      correct for the effects of axial astigmatism in the diffraction lens. It seems
      feasible that these same stigmators could also be used to form a series of
      'astigmatic' diffraction patterns. It is shown how this series of diffraction
      patterns could then be used to perform exit-surface wavefunction reconstruction.
      This has the advantage that the diffraction patterns are not resolution limited
      by the objective aperture as are images when performing exit-surface wavefunction
      reconstruction from a focal series. A scheme for carrying out phase
      reconstruction from a series of astigmatic diffraction patterns in an electron
      microscope is presented.

PMID- 15846036
TI  - A transition path for the pressure-induced wurtzite- to NaCl-type transformation
      described in Pna2(1).
AB  - Quite recently, two further mechanisms for the pressure-induced transition from
      the wurtzite to the NaCl type were proposed [Shimojo et al. (2004). Phys. Rev. B,
      70, 184111-1-6] but no symmetry information was given. It will be shown that a
      slight modification of one of the assumed transition pathways allows a
      crystallographic description on the basis of a deformation of a heterogeneous 4
      connected sphere packing in Pna2(1). All investigations were done with the help
      of the corresponding homogeneous packing in Pnma where the transition may be
      described as a deformation of a lonsdaleite configuration into a cubic primitive
      lattice cP. During the transformation, all sphere contacts are maintained. The
      new transition model is compared with the well known Cmc2(1) mechanism. Further
      related mechanisms can also be derived.

PMID- 15846037
TI  - Hexagonal and trigonal sphere packings. III. Trivariant lattice complexes of
      hexagonal space groups.
AB  - All types of homogeneous sphere packing and interpenetrating sphere packings and
      layers were derived that correspond to point configurations of the 15 trivariant
      hexagonal lattice complexes. The respective sphere packings are assigned to 147
      types. In total, sphere packings of 170 types can be realized with hexagonal
      symmetry. 103 types of sphere packing refer exclusively to trivariant hexagonal
      lattice complexes. For 23 of these types, the corresponding sphere packings can
      be generated only in hexagonal lattice complexes with less than three degrees of
      freedom or with trigonal or lower symmetry. In addition, seven types of
      interpenetrating sphere packings and two types of interpenetrating sphere layers
      were found. Interpenetrating 4.8(2) nets of spheres with 120 degrees angles
      between the nets were assumed to be not possible, so far. The sphere packings
      belonging to 85 of the 170 hexagonal types can be split up into parallel layers
      of spheres with mutual contact and can be characterized by symbols derived from
      those for the Shubnikov nets. The sphere packings of 135 hexagonal types may be
      subdivided into rod-like subsets of spheres with mutual contact. Such rods may be
      described by rolling up a plane net. Only 23 types of sphere packing cannot be
      symbolized on the basis of layers or rods of spheres with mutual contact.
      Examples are given for crystal structures that can be described by means of
      sphere packings.

PMID- 15846038
TI  - The partial structure with errors: a probabilistic treatment.
AB  - The method of the joint probability distribution functions has been applied to
      the case in which observed (with errors) and calculated structure factors are
      available, the latter referred to a part of the structure with finite errors in
      the coordinates, the thermal parameters and the scattering factors. Results
      obtained by other authors are confirmed and generalized. A new relationship is
      found to estimate the parameter sigmaA, affecting the reliability of the
      estimates of cos(varphi-varphip). Some practical applications are described.

PMID- 15846039
TI  - Statistical approach in cluster analysis of two-dimensional quasicrystals.
AB  - An analytical formula for the structure factor of Penrose tiling in the cluster
      approach was derived and tested. Probability distributions obtained for each
      Penrose position allow the number of different atoms that can decorate the
      cluster to be found. Calculations were performed in the average-unit-cell
      approach for Gummelt's cluster of 33 atoms, divided into three independent groups
      of atoms, and a kite cluster of 17 atoms, divided into seven independent groups.

PMID- 15846040
TI  - Isohedral simple tilings: binodal and by tiles with <or=16 faces.
AB  - All isohedral simple tilings of 3D Euclidian space by tiles with </=16 faces have
      been determined. There are no such tilings by polyhedra with less than 14 faces.
      For simple polyhedra with 14, 15 and 16 faces, there are respectively 10, 65 and
      434 that fill space and a total of 23, 136 and 710 distinct tilings. The tilings
      by 14-face polyhedra are described in detail as are binodal (vertex 2-transitive)
      isohedral simple tilings.

PMID- 15846041
TI  - The prior-derived F constraints in the maximum-entropy method.
AB  - The method of the prior-derived F constraints (PDC) enhances the quality of
      reconstructions of electron densities from X-ray diffraction data by the maximum
      entropy method (MEM). The method concentrates on artifacts arising due to
      inaccurate extrapolation of non-measured data by the MEM. While these artifacts
      are unavoidable, when a flat prior is used, they can be effectively suppressed,
      if the prior information about the structure is known in the form of a procrystal
      prior electron density. The missing, usually high-angle, structure factors can be
      effectively substituted by the structure factors derived from the procrystal
      prior. This approach eliminates the occurrence of spurious peaks in the
      difference electron densities in the vicinity of the atomic positions. The method
      is illustrated with a simple one-dimensional example. Its use is then
      demonstrated on simulated data of oxalic acid dihydrate and on experimental data
      of sodium nitrite.

PMID- 15846042
TI  - Diffraction with wavefront curvature: a path to unique phase recovery.
AB  - Modern X-ray optics is able to produce very tightly focused beams. The size of
      these focused spots is comparable to the scale of large molecules and therefore
      to the lattice spacing of crystals of these molecules. In this case, the phase of
      the illuminating beam may vary on the scale of the lattice and conventional
      diffraction theory needs to be modified. In this paper, coherent diffraction by
      non-planar beams is considered and it is shown that it is possible to uniquely
      recover the phase of the diffraction pattern.

PMID- 15846043
TI  - Tables of properties of magnetic subperiodic groups.
AB  - Tables of crystallographic properties of the magnetic subperiodic groups, i.e.
      the 31 magnetic frieze-group types, the 394 magnetic rod-group types and the 528
      magnetic layer-group types are presented. The content and format is similar to
      that of non-magnetic subperiodic groups and space groups given in International
      Tables for Crystallography. Additional content for each group type includes a
      diagram of general positions with corresponding general magnetic moments, Seitz
      notation used as a second notation for symmetry operations, and general and
      special positions listed with the components of the corresponding magnetic
      moments allowed by symmetry.

PMID- 15846044
TI  - Detection of the hyaluronan receptor CD44 in the bovine oviductal epithelium.
AB  - Hyaluronan is involved in fundamental reproductive events such as sperm storage
      in the female reproductive tract, fertilization, and early embryo development,
      these functions are presumably mediated by its major cell surface receptor, CD44.
      The present study was conducted to investigate the presence and localization of
      CD44 in the bovine oviductal epithelium, using immunohistochemical and Western
      blot methods on tissue sections and epithelial cell extracts collected from the
      uterotubal junction (UTJ), isthmus, and ampulla of animals in the oestrus or
      luteal phase of the oestrous cycle. While positive immunolabelling for CD44 was
      found on the ad-luminal surface and supra-nuclear region of epithelial cells in
      all tubal segments investigated, in the UTJ, there were epithelial cells in which
      the entire cytoplasm positively stained. We found no differences in terms of CD44
      positive staining between the different stages of the oestrous cycle. Presence of
      CD44 was detected by Western blotting in the tubal epithelium as a single band at
      200 kDa. Although it appeared in all tubal segments, the expression of CD44
      protein was more accentuated in the sperm reservoir (UTJ) than in the other
      segments. This is the first time CD44 has been detected in the epithelium of the
      tubal sperm reservoir in cattle, suggesting a pathway for the action of
      hyaluronan in this segment.

PMID- 15846045
TI  - Immunolocalization of von Willebrand factor and vascular endothelial growth
      factor during follicular atresia in the swamp buffalo ovary.
AB  - The aim of this study was to investigate the distribution pattern of von
      Willebrand factor (vWF) and vascular endothelial growth factor (VEGF) in the
      healthy antral and atretic follicles of Philippine swamp buffaloes (SB) in
      comparison with Holstein-Friesian cows (HF). Paraffin sections of healthy
      follicles and atretic follicles at various stages were immunostained with vWF
      antibody and VEGF antibody. The density of vWF-positive capillary vessels in the
      theca interna significantly increased as atresia progressed in SB, whereas the
      density significantly decreased in late atretic follicles compared with advanced
      ones in HF. On the other hand, the area of vWF-positive capillary vessels in the
      theca interna significantly increased as atresia progressed in both SB and HF.
      Immunoreactions of VEGF in the granulosa cells (in all follicle types) were
      observed in both SB and HF. In the granulosa layer, a reduction in the VEGF
      immunoreaction was noted as follicles progressed from healthy to advanced atretic
      follicles in both animals. Granulosa cells (in both SB and HF) showed a higher
      immunopositive staining than theca cells. In the theca interna, VEGF
      immunostaining diminished as follicles progressed to the late atretic follicles
      in both animals. These results indicate that during atresia, changes of vWF
      expression are the opposite of VEGF expression in SB. Both vWF and VEGF are
      suggested to be associated with follicular atresia in SB.

PMID- 15846046
TI  - 3-D ultrastructural distribution of collagen in human placental villi at term in
      relation to vascular tree.
AB  - In order to understand the 3-D distribution of collagen in relation to
      vascularization, chorionic villi of human placentae, belonging to normal
      pregnancies at term, were studied by scanning electron microscopy (SEM) after
      alkali maceration techniques, and by transmission electron microscopy (TEM). The
      villous tree appeared made of an uninterrupted structure of collagen fibres. The
      collagen fibres connected the chorionic villi axis with their basal plates and
      organised differently according to the various levels of villous branching. The
      collagen of stem villi showed copious fibres. The external fibres (facing the
      villous surface) were arranged mainly longitudinally. The central core of the
      villi (inner fibres) were arranged concentrically around the wall of the fetal
      vessels. Both external and internal fibres formed stratified lamellae or small
      parallel bundles. The inner core of stem villi showed small holes housing
      capillary spaces. Mature intermediate and terminal villi showed a scarce amount
      of collagen arranged in thin concentric layer within the villous core,
      surrounding numerous dilated capillary and sinusoid spaces.These observations
      demonstrated that the extracellular matrix of human chorionic villi is highly
      compartmentalised and shows a variable structural 3-D distribution depending on
      the branching level of the villous tree, such a distribution ensures the most
      favourable microenvironment for feto-maternal exchanges and it is likely able to
      provide a modulated support to the developing chorionic fetal vessels and
      trophoblastic layer as well.

PMID- 15846047
TI  - Molecular regulation of gonadotropin secretion by gonadotropin-releasing hormone
      in salmonid fishes.
AB  - Gonadotropin-releasing hormone (GnRH) plays a central role in the control of
      reproductive function in vertebrates. In salmonids, salmon GnRH (sGnRH) secreted
      by preoptic GnRH neurons regulates gonadal maturation through stimulation of
      synthesis and release of pituitary gonadotropins (GTHs). In addition, several
      lines of our evidence indicate that sGnRH is involved in spawning behavior, and
      serves to integrate the gonadal maturation with the reproductive behavior. A
      growing number of studies show that the effects of GnRH are mediated by multiple
      subtypes of GnRH receptors, successive multiple signaling pathways, and finally
      multiple transcription factors which act cooperatively to stimulate transcription
      of GTH subunit genes. This complex regulatory system of the action of GnRH may
      serve as a molecular basis of divergent physiological strategies of reproductive
      success in various vertebrate species. In this article, recent data on the
      molecular mechanisms of action of GnRH are reviewed with special reference to the
      regulation of synthesis and release of GTHs in the pituitary of salmonids to
      elucidate the multifunctional action of GnRH.

PMID- 15846048
TI  - Settlement-competency period of planulae and genetic differentiation of the
      scleractinian coral Acropora digitifera.
AB  - Broadcast-spawning corals expel eggs and sperm, and the fertilized eggs develop
      into planulae in the water column. As these sessile corals generally disperse
      during the planktonic larval stage, their larval characteristics (e.g., survival
      and settlement rates) are thought to be important for their dispersal. Although
      some studies of coral larval dispersal have focused on the maximum time that
      larvae can remain viable and settle, the relevance of this maximum settlement
      competency period for long distance dispersal remains unclear. To examine the
      relationship between competency periods and genetic differentiation, we performed
      laboratory experiments to investigate settlement rates of planulae and determine
      the degree of genetic differentiation in Acropora digitifera in the Ryukyu
      Archipelago, southern Japan. In addition, we compared our findings to published
      data for A. tenuis, which was studied using our methods. Our results indicated
      that the maximum settlement competency period was lower in A. digitifera planulae
      (54 days) than in A. tenuis (69 days) planulae. The mean survival rates at 45
      days and 59 days after spawning were less than 10%. Furthermore, percentages of
      planulae that remained viable and settle at 30 days after spawning (survival rate
      x settlement rates at 30 days) were approximately 18% and 25% in A. digitifera
      and A. tenuis, respectively. By contrast, gene flow (N(e)m: number of migrations
      per generation) was significantly higher in A. digitifera (7.8 to 41.4) than in
      A. tenuis (3.1 to 22.5). These results indicate that the settlement competency
      period and survival rates are unlikely to be robust predictors of gene flow.
      Overall, we detected significant genetic differentiation between Kerama and
      Okinawa in A. digitifera. As direct observation of planula dispersal between
      Kerama and Okinawa has been reported, we concluded that genetic mixing is not
      complete, but that some localized planulae may disperse from Kerama to Okinawa
      via a specific current depending on reef or locality.

PMID- 15846049
TI  - Unexpected ceiling of genetic differentiation in the control region of the
      mitochondrial DNA between different subspecies of the ayu Plecoglossus altivelis.
AB  - Sequence analyses of the non-coding, control region (CR) and coding region of the
      ND4-tRNA(Ser) genes in the mitochondrial DNA (mtDNA) were conducted for
      populations of the ayu Plecoglossus altivelis altivelis and the Ryukyu-ayu P. a.
      ryukyuensis. The level of genetic differentiation between the two subspecies
      evaluated from the CR data was substantially low, when comparing with that
      estimated from ND4-tRNA(Ser) gene region data, as well as those from nuclear
      genome data sets. By contrast, the differentiation between subspecies in the ND4
      tRNA(Ser) gene region was substantial, being consistent with the results from the
      previous nuclear genome analyses. Results of UPGMA and minimum spanning network
      analyses also implied the unexpected ceiling of genetic differentiation in the
      CR. These results suggest that the CR does not reflect accurately the level of
      overall genetic differentiation between the populations of the ayu, but other
      coding regions of the mtDNA do reflect it so that the mtDNA on the whole may
      function as a rich source of useful markers for genetic assessment of populations
      of this species.

PMID- 15846050
TI  - Copepod parasites of the fatheads (pisces, psychrolutidae) and their implication
      on the phylogenetic relationships of psychrolutid genera.
AB  - Nine species of psychrolutids kept in the Marine Zoology of Hokkaido University
      were found to carry eight species of copepod parasites. The parasites and their
      hosts are: Bobkabata kabatabobbus Hogans and Benz, 1990 on Malacocottus zonurus
      Bean; Chondracanthus parvus n. sp. on Eurymen gyrinus Gilbert and Burke;
      Chondracanthus yabei n. sp. on Dasycottus setiger Bean and M. zonurus; Ch. yanezi
      Atria, 1980 on Psychrolutes phrictus Stein and Bond; Caligus similis n. sp. on
      Neophrynichthys latus (Hutton); Clavella adunca (Strom, 1762) on M. zonurus;
      Neobrachiella amphipacifica Ho, 1982 on Ambophthalmos angustus (Nelson),
      Cottunculus sp., D. setiger, Ebinania brephocephala (Jordan and Starks), E.
      vermiculata Sakamoto, and P. phrictus; and Naobranchia occidentalis Wilson, 1915
      on D. setiger and M. zonurus. Chondracanthus parvus is closest to Ch. deltoideus
      Fraser, 1920, but differs from it in having only one pair of small knobs on the
      head and carrying a pair of lateral processes on the second pediger.
      Chondracanthus yabei resembles Ch. yanezi Atria, 1980, but can be distinguished
      from it by the presence of three, low protrusions on the mid-dorsal surface of
      the trunk; besides, maxillule also shows difference. As the name indicates, C.
      similis resembles several species of Caligus that bear a short abdomen and a
      formula of I; IV on the exopod of leg 4. However, it can be separated from them
      by the combination of the following characters: a genital complex distinctly
      smaller than the cephalothoracic shield, a pair of relatively short caudal rami,
      a smooth dentiform process on maxillule, and a pair of truncate tines on sternal
      furca. Analysis of the occurrence of Chondracanthus on the psychrolutid fishes
      shows that the phylogeny of Chondracanthus is in congruence with that of the
      Psychrolutidae. It implies that parasitism of Chondracanthus occurred after the
      Dasycottus clade diverged off the main stock of the Psychrolutidae and the
      occurrence of Ch. yabei on D. setiger is resulted from a later colonization.

PMID- 15846051
TI  - Molecular phylogeny of avian genus Syrmaticus based on the mitochondrial
      cytochrome B gene and control region.
AB  - Mitochondrial DNA cytochrome b (cyt b) and control region (CR) nucleotide
      sequences were used to study the molecular phylogeny of the genus Syrmaticus. We
      found that the substitution rates among the three codon positions of cyt b were
      heterogeneous and the transition-transversion ratio was highly biased. As to CR
      sequences of the genus, most variable sites were in the peripheral domains. All
      molecular phylogenetic trees based on the two genes showed that: 1) the
      Syrmaticus was monophyletic and included five species with the following
      cladistic relationship: (S. reevesii, (S. soemmerringii, (S. mikado, (S. humiae
      and S. ellioti)))). Using the TN genetic distance of cyt b, we inferred the
      divergence time of the five species according to putative molecular clock and
      found that values were largely in agreement with the geological scenarios. The
      origin and speciation processes of the studied group were inferred by combining
      molecular and biogeographical evidences.

PMID- 15846052
TI  - Behavioural and energetic responses to body state in male and female barn
      swallows (Hirundo rustica).
AB  - Females and males often have different roles when attending young. The factors
      responsible for shifts in the balance of effort when both sexes provision their
      young are not clear. This study asked if sex-specific behaviour and provisioning
      rules in barn swallows (Hirundo rustica) were dependent on individual body-state
      or affected by the state of their provisioning partner. To assess this male and
      female barn swallows underwent overnight warming manipulations whilst
      provisioning 10-14 day old nestlings, a time when energetic demands are maximal.
      The overnight warming treatment reduced thermoregulatory costs and provided birds
      with extra energy reserves at dawn. Only one member of a pair was manipulated in
      this way, whilst their partners were left un-manipulated to assess their response
      to their partner's elevated body-state. The energetic and behavioural responses
      to these manipulations were followed over the subsequent 24-h. I found that
      warmed male and female barn swallows increased their energy expenditure and nest
      visitation rates to the same extent after manipulation, implying a trade-off in
      resource allocation, which was biased towards reproductive effort. There was no
      effect of gender. Males paired with manipulated females showed no energetic or
      behavioural adjustments, however, females paired with manipulated males tended to
      increase both energy expenditure and nest visitation. This study provides
      evidence that energy reserves constrain behaviour, and that male and female
      swallows normally follow the same state-dependent rules when provisioning young.

PMID- 15846053
TI  - Externally measured condition versus internal organ mass in the caecilian
      Gegeneophis ramaswamii (Amphibia: Gymnophiona: Caeciliidae).
AB  - The relationship between externally measured condition (mass x length(-3)) and
      the mass of internal major organs in the caecilian Gegeneophis ramaswamii is
      investigated, based on a collection of 67 specimens from three southern Indian
      localities in the early and mid-monsoon. Condition in juveniles (< 90 mm total
      length) is higher than in subadults (90-170 mm) and adults (> 170 mm). The
      relationship between condition and total length is consistent in subadults, but
      variable in adults, and these differences indicate that the delimitation of these
      ontogenetic stages has some biological meaning. Adult females have fat bodies
      which fluctuate in mass, but not in relation to their body size. On average,
      adult females have heavier fat bodies and lighter gut contents than adult males,
      but there are no significant differences between subadult males and females.
      Gravid females are predicted to have a notably greater condition. There is no
      consistent relationship between condition and any major internal organ, but there
      is some significant variation among samples grouped by sampling time and
      locality. More sampling throughout the year is required to clarify the complex
      relationships between condition and internal organs, and before externally
      measured condition from ecological studies of living animals can be readily
      interpreted. However, its utility in helping to differentiate between ontogenic
      classes may be of immediate use.

PMID- 15846054
TI  - Vitellogenin-immunohistochemistry in the liver and the testis of the medaka,
      Oryzias latipes, exposed to 17beta-estradiol and p-nonylphenol.
AB  - Vitellogenin (VTG) produced in male fish has been used for a biomarker to study
      endocrine disrupters. However, the characteristics of VTG produced in male fish
      have not been studied well. In this study, we investigated the localization of
      VTG in the liver and the testis of male medaka (Oryzias latipes) treated with
      17beta-estradiol (E2) and p-nonylphenol (NP). The male fish were exposed to 1
      microg/L E2 and 500 microg/L NP for 1-12 days. Control groups were kept in water
      including only vehicle. The frozen sections of the liver and the testis were
      stained with immunohistochemical methods using an antiserum against medaka VTG as
      the first antibody. In the E2 and NP treated liver, the hepatocytes showed
      immunoreactivity. In particular, the cytoplasm close to the cell membrane
      surrounding the sinusoids was strongly immunopositive. In the testis of both
      treatments, the interstitial tissues and the cells (spermatocytes) in the
      seminiferous tubules were immunopositive. The concentration of VTG became
      gradually higher in both tissues with longer treatments. These results suggest
      that germ cells in the testis treated with E2 and NP are able to incorporate and
      accumulate VTG.

PMID- 15846055
TI  - The morphological and histological characters of the male external genitalia of
      the house musk shrew, Suncus murinus.
AB  - External genitalia are the reproductive organs necessary for efficient copulation
      and internal fertilization in various mammalian species. Their morphogeneses
      display significant morphological and developmental differences among species.
      The house musk shrew, Suncus murinus (hereafter described as suncus) is a species
      of the order Insectivora, which has been considered as primitive and one of the
      earliest eutheria phylogenetically. Comparative anatomical analyses of
      phylogenetically different mammals will contribute to the better understanding of
      morphological diversity of external genitalia. This study performed various
      anatomical and histological analyses concerning the organization of the external
      genitalia of male suncus. It was shown that the external genitalia of suncus
      possessed a muscular structure, which we proposed as musculus ischiocavernosus
      dorsalis of suncus. The musculus ischiocavernosus dorsalis is originated from the
      inner surface of the tuber ischiadicum and was allocated adjacent to the corpus
      cavernosum penis. In addition, a pair of alpha-smooth muscle actin positive
      muscles was located bilaterally to the urethra. This unique morphology of the
      external genitalia of suncus males may provide a unique model system to
      investigate genital morphogenesis.

PMID- 15846056
TI  - Organization of the sensory and motor nuclei of the glossopharyngeal and vagal
      nerves in lampreys.
AB  - Anterograde and retrograde transport of horseradish peroxidase was used to
      examine the afferent and efferent projections of the glossopharyngeal and vagal
      nerves in the lamprey, Lampetra japonica. Except for the ganglion cells and
      motoneurons, the distribution patterns of HRP-positive elements differed little
      between the two nerves. Afferent fibers mainly terminated in the ipsilateral
      cerebellar area, medial octavolateralis nucleus, and between the ventral
      octavolateralis nucleus and descending tract and nucleus of the trigeminal nerve
      (dV). In the cerebellar area, most of the labeled fibers were located in the
      molecular zone, but some penetrated into the granular zone. In the rostral part
      of the medial octavolateralis nucleus, labeled fibers coursed from the middle to
      the lateral area, and in the caudal part, they were localized in the dorsal area
      of the nucleus. In the area between the dV and ventral octavolateralis nucleus,
      labeled fibers coursed near the dorsal margin of the rostral part of the dV, and
      in the caudal part, they shifted dorsally. Ganglion cells and motoneurons of each
      nerve were also labeled.

PMID- 15846057
TI  - Two new species of ochridacyclops (Kiefer, 1937) (Copepoda, Cyclopoida) from
      Kenya and Nepal.
AB  - Two species of cyclopoid copepods, Ochridacyclops kenyaensis sp. nov. and O.
      nepalensis sp. nov. are described as the first records of this genus from Kenya
      and Nepal, respectively. Ochridacyclops kenyaensis can easily be distinguished
      from its congeners by having a rounded and blunt distal end of the outer terminal
      seta (IV) on the caudal rami, and by the inner terminal spine being about equal
      in length to the outer terminal spine on the endopod of leg 4. Ochridacyclops
      nepalensis can easily be distinguished from other members of the genus by having
      two spines on exopodal segment 3 of leg 1, and by the proportions of the caudal
      rami, which are 3.4 times longer than wide.

PMID- 15846058
TI  - Taxonomic relationships within the pan-oriental narrow-mouth toad Microhyla
      ornata as revealed by mtDNA analysis (Amphibia, Anura, Microhylidae).
AB  - A molecular phylogenetic survey was conducted using mtDNA sequences of 12S and
      16S rRNA, and cyt-b genes to examine taxonomic relationships among populations of
      the Pan-Oriental microhylid, Microhyla ornata, from India, Bangladesh, Thailand,
      Laos, China, Taiwan, and the Ryukyu Archipelago of Japan. Two discrete clades are
      recognized within this species, one consisting of populations from India and
      Bangladesh, and the other encompassing the remaining populations. In the latter
      clade, populations from the Ryukyu Archipelago are clearly split from the rest
      (populations from Taiwan and the continent) with considerable degrees of genetic
      differentiations. Each of the three lineages is judged to represent a good
      species, and the name Microhyla ornata is restricted to the South Asian
      populations. For the populations from Taiwan and a wide region from China to
      Southeast Asia, the name Microhyla fissipes should be applied, whereas the Ryukyu
      populations are most appropriately referred to as Microhyla okinavensis, although
      further substantial genetic differentiations are recognized among some island
      group populations within this last species.

PMID- 15846059
TI  - Maspin regulates hypoxia-mediated stimulation of uPA/uPAR complex in invasive
      breast cancer cells.
AB  - Maspin, a unique serine proteinase inhibitor (serpin), plays a key role in
      mammary gland development and is silenced during breast cancer progression.
      Maspin has been shown to inhibit tumor cell motility and invasion in cell
      culture, as well as growth and metastasis in animal models. In this study, we
      investigated the effect of maspin on the regulation of hypoxia-induced expression
      of urokinase-type plasminogen activator (uPA) and its receptor (uPAR), with
      respect to invasive potential in metastatic breast cells MDA-MB-231. We
      hypothesized that maspin can neutralize or mitigate hypoxia-induced expression of
      uPA/uPAR in metastatic breast cancer cells, resulting in suppression of their
      invasive potential. To test our hypothesis, we employed the highly invasive MDA
      MB-231 breast cancer cells that are devoid of maspin, and transfected them with
      the maspin gene, and then determined the effect of hypoxia on uPA/uPAR
      expression. Normal mammary epithelial cells 1436N1 were used as a control. Our
      findings demonstrate that maspin downregulated the basal and hypoxia-induced
      uPA/uPAR expression and reduced the stimulatory effect of hypoxia on the in vitro
      invasive ability of MDA-MB-231-cells. In addition, maspin also inhibited the
      enzymatic activity of secreted and cell associated uPA in MDA-MB-231 cells. These
      results indicate that maspin inhibits hypoxia-induced invasion of metastatic
      breast cancer cells by blocking the uPA system, thus illuminating an important
      molecular pathway for therapeutic consideration.

PMID- 15846060
TI  - ATM activation in normal human tissues and testicular cancer.
AB  - The ATM kinase is a tumor suppressor and key regulator of biological responses to
      DNA damage. Cultured cells respond to genotoxic insults that induce DNA double
      strand breaks by prompt activation of ATM through its autophosphorylation on
      serine 1981. However, whether ATM-S1981 becomes phosphorylated in vivo, for
      example during physiological processes that generate DSBs, is unknown. Here we
      produced phospho-specific monoclonal antibodies against S1981-phosphorylated ATM
      (pS-ATM), and applied them to immunohistochemical analyses of a wide range of
      normal human tissues and testicular tumors. Our data show that regardless of
      proliferation and differentiation, most human tissues contain only the S1981
      nonphosphorylated, inactive form of ATM. In contrast, nuclear staining for pS-ATM
      was detected in subsets of bone-marrow lymphocytes and primary spermatocytes in
      the adult testes, cell types in which DSBs are generated during physiological
      V(D)J recombination and meiotic recombination, respectively. Among testicular
      germ-cell tumors, an aberrant constitutive pS-ATM was observed especially in
      embryonal carcinomas, less in seminomas, and only modestly in teratomas and the
      pre-invasive carcinoma-in-situ stage. Compared with pS-ATM, phosphorylated
      histone H2AX (gammaH2AX), another DNA damage marker and ATM substrate, was
      detected in a higher proportion of cancer cells, and also in normal fetal
      gonocytes, and a wider range of adult spermatocyte differentiation stages.
      Collectively, our results strongly support the physiological relevance of the
      recently proposed model of ATM autoactivation, and provide further evidence for
      constitutive activation of the DNA damage machinery during cancer development.
      The new tools characterized here should facilitate monitoring of ATM activation
      in clinical specimens, and help develop future treatment strategies.

PMID- 15846061
TI  - The epithelial-mesenchymal transition (EMT) and colorectal cancer progression.
AB  - During embryonic development, epithelial cells must escape the structural
      constraints imposed by tissue architecture and adopt a phenotype more amenable to
      cell movement, a process known as the epithelial-mesenchymal transition (EMT).
      The progression of carcinomas to invasive and metastatic disease may also involve
      localized occurrences of EMT. However, data that support the actual occurrence of
      EMT in specific carcinomas and the relevance of this process to the progression
      of these tumors had been scant. This review highlights recent studies that
      substantiate the importance of the EMT to colorectal carcinoma. Specifically, a
      novel model for studying the EMT of colorectal carcinoma has been used to gain
      insight into the nature of the EMT itself and to identify molecular events that
      contribute to disease progression. Although loss of E-cadherin function is a
      primal event for the EMT, the expression of specific integrins such as
      alpha(v)beta6 as a consequence of the EMT enables invasive cells to interact with
      interstitial matrices and to sustain activation of TGF-beta. Of note,
      alpha(v)beta6 expression in tumors is a marker of cells that have undergone an
      EMT and it is prognostic for tumors that will progress more rapidly to terminal
      disease. The EMT also induces autocrine signaling involving VEGF and Flt-1 that
      enable invasive cells to become 'self-sufficient' for survival. Thus, the EMT
      appears to be an integral component of colorectal cancer progression and its
      analysis can yield novel targets for prognosis and therapy.

PMID- 15846062
TI  - A novel WISp39 protein links Hsp90 and p21 stability to the G2/M checkpoint.
AB  - Transcriptional regulation of the p21(Cip1) cyclin-dependent kinase inhibitor is
      a well-established mechanism by which the cell orchestrates a proper spatial and
      temporal cell cycle progression. Now, in the January 2005 issue of Molecular Cell
      (2005; Vol 17, 237-49), a study by Jascur et al identifies a novel multi-protein
      complex that is critical in contributing to a p53-dependent G2 cell cycle
      checkpoint. The authors demonstrate the significance of stabilizing the p21
      protein in the context of this complex.

PMID- 15846063
TI  - Targeting cancer cells with DNA-assembled dendrimers: a mix and match strategy
      for cancer.
AB  - The unique biology of cancer requires the development of a multifunctional drug
      delivery system which can be efficiently manufactured to target subtle molecular
      alterations that distinguish a cancer cells from the many types of healthy cells
      found in the body. We sought to produce dendrimers conjugated to different bio
      functional moieties [fluorescein (FITC) and folic acid (FA)], then link them
      together using complementary DNA oligonucleotides to produce clustered molecules
      that target cancer cells that over-express the high affinity folate receptor.
      This study demonstrates a unique molecular platform based on the DNA-directed
      assembly of dendritic polymers for the delivery of different agents to cancer
      cells. While only nanometers in diameter (the size of proteins), this DNA-linked
      dendrimer nanocluster platform is considered to allows for the delivery of drugs,
      genetic materials, and imaging agents to cancer cells, offering the potential for
      developing combinatorial therapeutics.

PMID- 15846064
TI  - Better to give than receive: my exciting journey in science.

PMID- 15846065
TI  - Haspin: a mitotic histone kinase required for metaphase chromosome alignment.
AB  - The fidelity of chromosome segregation during cell division is critical to
      maintain genomic stability and to prevent cancer and birth defects. A key set of
      kinases that regulates this process has been identified and characterized over
      the last few years, including the Aurora, Polo and Nek families. Recently we
      proposed that a little-studied kinase known as haspin is a new member of this
      important group. During mitosis haspin is phosphorylated, associates with the
      chromosomes, centrosomes and spindle, and is responsible for phosphorylation of
      histone H3 at threonine-3. Depletion of haspin using RNA interference prevents
      normal alignment of chromosomes at metaphase, suggesting that haspin plays a
      crucial role in chromosome segregation. Here we discuss possible mechanisms of
      haspin action and the function of histone phosphorylation in mitosis. We also
      outline some of the questions raised by these new findings and consider what role
      haspin might play in cancer.

PMID- 15846066
TI  - Regulatory T cells and cytokines in malignant pleural effusions secondary to
      mesothelioma and carcinoma.
AB  - Immunotherapy against a variety of malignancies, including pleural-based
      malignancies, has shown promise in animal models and early human clinical trials,
      but successful efforts will need to address immunosuppressive factors of the
      tumor and host, particularly certain cytokines and CD4(+) CD25(+) regulatory T
      cells (Treg). Here, we evaluated the cellular and cytokine components of
      malignant pleural effusions from 44 patients with previously diagnosed
      mesothelioma, non-small cell lung cancer (NSCLC), or breast cancer and found
      significant differences in the immune profile of pleural effusions secondary to
      mesothelioma vs. carcinoma. Although a high prevalence of functionally
      suppressive CD4(+) CD25(+) T cells was found in carcinomatous pleural effusions,
      mesothelioma pleural effusions contained significantly fewer CD4(+) CD25(+) T
      cells. Activated CD8(+) T cells in pleural fluid were significantly more
      prevalent in mesothelioma than carcinoma. However, there is clear patient-to
      patient variability and occasional mesothelioma patients with high percentages of
      CD4(+) CD25(+) pleural effusion T cells and low percentages of CD8(+) CD25(+)
      pleural effusion T cells can be identified. Mesothelioma pleural effusions
      contained the highest concentrations of the immunosuppressive cytokine
      transforming growth factor (TGF)-beta. Thus, the contribution of cellular and
      cytokine components of immunosuppression associated with malignant pleural
      effusions varies by tumor histology and by the individual patient. These results
      have implications for the development of immunotherapy directed to the malignant
      pleural space, and suggest the need to tailor immunotherapy to overcome
      immunosuppressive mechanisms in tumor environments.

PMID- 15846067
TI  - Kinase-addiction and bi-phasic sensitivity-resistance of Bcr-Abl- and Raf-1
      expressing cells to imatinib and geldanamycin.
AB  - By activating anti-apoptotic factors (e.g., Hsp70, Raf-1, Bcl-xL), Bcr-Abl blocks
      apoptotic pathways at multiple levels, thus rendering leukemia cells resistant to
      chemotherapeutic agents such as doxorubicin (DOX). In Bcr-Abl-transfected HL60
      (HL/Bcr-Abl) cells, procaspase-9 was increased and partially processed. The Bcr
      Abl inhibitor imatinib (Gleevec, STI-571) released the apoptotic stream. Also,
      HL/Bcr-Abl cells were hyper-sensitive to geldanamycin (GA), which depletes Bcr
      Abl and Raf-1. Raf-1 and Bcr-Abl-transfected FDC-P1 hematopoietic cells were
      selectively sensitive to GA and imatinib, respectively. Remarkably, cell clones
      with high levels of Bcr-Abl that could not be depleted by GA were relatively
      resistant to both GA and imatinib. GA and flavopiridol sensitized such resistant
      cells to imatinib. These data suggest bi-phasic sensitivity to mechanism-based
      therapeutic agents. Although Bcr-Abl renders cells hyper-sensitive, an excess of
      Bcr-Abl results in resistance (due to the remaining activity). We discuss
      therapeutic approaches to overcome bi-phasic resistance to mechanisms-based
      agents.

PMID- 15846068
TI  - Regulation of multidrug resistance by ribosomal protein l6 in gastric cancer
      cells.
AB  - Ribosomal proteins (RP) L6 was previously identified as an up-regulated gene in
      multidrug-resistant gastric cancer cells SGC7901/ADR comparing to its parental
      cells SGC7901 by subtractive hybridization. The aim of this study was to explore
      the roles of RPL6 in multidrug resistance (MDR) in gastric cancer cells. Northern
      and Western blot analysis confirmed that RPL6 was overexpressed in SGC7901/ADR
      cells. By gene transfection, RPL6 was genetically upregulated in SGC7901 or down
      regulated in SGC7901/ ADR cells. Upregulation of RPL6 was associated with
      enhanced resistance to multiple anticancer drugs (adriamycin, vincristine,
      etoposide, 5-fluorouracil and cisplatin) and to adriamycin-induced apoptosis.
      Downregulation of RPL6 reversed MDR and sensitized cells to adriamycin-induced
      apoptosis. Alteration of RPL6 showed no obvious influence on intracellular
      adriamycin accumulation, glutathione content and expression of glutathione S
      transferase. RPL6 could upregulate Bcl-2 and downregulate Bax in cells. Together,
      this work demonstrates that RPL6 could regulate MDR in gastric cancer cells by
      suppressing drug-induced apoptosis.

PMID- 15846069
TI  - Immortalizing the complexity of cancer metastasis: genetic features of lethal
      metastatic pancreatic cancer obtained from rapid autopsy.
AB  - The virtual lack of well-characterized metastatic pancreatic cancer tissues for
      study has limited systematic studies of the metastatic process of this deadly
      disease. To address this important issue, we have instituted a rapid autopsy
      protocol for the collection of high quality tissues from patients with metastatic
      pancreatic cancer, called the Gastrointestinal Cancer Rapid Medical Donation
      Program (GICRMDP). At the time of preparation of this manuscript, 20 patients
      with metastatic pancreatic cancer and one patient with metastatic colon cancer
      have undergone a rapid autopsy in association with the GICRMDP. The average time
      interval achieved for these 21 patients was 8.0 hours, with more than 500
      individual samples of matched high quality primary and metastatic pancreatic
      cancer tissues, peritoneal/pleural fluid and blood obtained so far. For the first
      four patients in which the autopsy was performed in <6 hours, we have
      successfully xenografted the primary tumor and/or two to four independent matched
      metastases from a variety of target organ sites, with a take rate of almost 60%
      for the first 26 xenografted tumors attempted. In an initial survey of KRAS2,
      TP53 and DPC4 genetic status in lethal metastatic pancreatic cancers, activating
      KRAS2 mutations were detected in 82% of cases and inactivating TP53 mutations in
      55% of cases, consistent with rates of genetic alteration of these genes in early
      stage pancreatic cancers. However, DPC4 inactivation was found in 75% of patients
      analyzed, suggesting that genetic inactivation of the DPC4 tumor suppressor gene
      continues to be selected for with growth at the primary site and metastatic
      spread to other organs. The invaluable tissue resources generated by the success
      of the GICRMDP will provide an unparalleled resource for study of metastatic
      pancreatic cancer and of the metastatic process in general.

PMID- 15846070
TI  - Differential enhancement of a cutaneous HPV promoter by DeltaNP63alpha, Jun and
      mutant p53.
AB  - The mechanism through which cutaneous papillomaviruses induce lesions is largely
      unknown. Ectopic expression of the DeltaNp63alpha isoform highly increased the
      viral promoter activity. The co-expression of c-Jun mediated and increased the
      DeltaNp63alpha activity by binding to the AP-1 site in an enhancer region of the
      HPV 20 URR. This strong activation by DeltaNp63alpha is diminished in the
      presence of wtp53 and abolished by the simultaneous expression of "hot-spot"
      mutant p53 R248W. We demonstrate that c-Jun is responsible for the viral promoter
      activation through its direct interaction with both DeltaNp63alpha and wtp53. The
      downregulation by p53 mutant R248W is accompanied by reduced protein levels of
      DeltaNp63alpha and phosphorylated c-Jun. The data presented in this study provide
      insight into a possible mechanism through which these cellular proteins may
      modulate a cutaneous papillomavirus genome to induce viral replication, latent
      infection or malignant transformation.

PMID- 15846071
TI  - Why cancer centers matter.

PMID- 15846072
TI  - RIalpha influences cellular proliferation in cancer cells by transporting RFC40
      into the nucleus.
AB  - The regulatory subunit (RIalpha) of cAMP-dependent Protein Kinase A (PKA) is
      overexpressed in a variety of tumors and carcinomas such as renal cell
      carcinomas, pituitary tumors of the rat, malignant osteoblasts, colon carcinomas,
      serous ovarian tumors and primary human breast carcinomas. However, the direct
      relation between overexpression of RIalpha and malignancy is still unclear. We
      have recently identified a novel interaction between RIalpha and RFC40, the
      second subunit of Replication Factor C (RFC), and have demonstrated that this
      interaction may be associated with cell survival. Coincidentally, RFC40 is
      overexpressed in gestational trophoblastic diseases such as choriocarcinomas.
      This study was undertaken to investigate a possible functional role for both
      these proteins together, in DNA replication and cellular proliferation. In the
      course of this study, a nonconventional nuclear localization signal was
      identified for RIalpha. Nuclear transport of RFC40 was found to be dependent on
      RIalpha, and this transport appeared to be a crucial step for cell cycle
      progression from G1 to S phase. Impairment in the nuclear transport of RFC40 by
      RIalpha arrested cells in G1 phase. These findings provide evidence for a
      previously unknown mechanism for the nuclear transport of RFC40 and also for a
      novel mechanism for cellular proliferation.

PMID- 15846073
TI  - Mechanism of first cleavage specification in the mouse egg: is our body plan set
      at day 0?
AB  - In most animals the body axis is specified in the egg. Because of their highly
      regulative capacity after experimental manipulations, mammalian preimplantation
      embryos have long been thought to be an exception to this rule, lacking polarity
      until the blastocyst stage. However, it has recently been suggested that the
      embryonic-abembryonic (Em-Ab) axis of the mouse blastocyst arises perpendicular
      to the first cleavage plane. Considering the second polar body (2pb) as a
      stationary marker for the "animal pole (A-pole)" during preimplantation
      development, the authors concluded that the polarity of the mouse embryo is
      already specified in the egg, as is the case for most non-mammalian animals.
      However, the results of our recent time-lapse recordings have shown(8) that in
      50% of the embryos the first cleavage occurs at a considerable distance from the
      "animal-vegetal (A-V) axis" and that the 2pb moves towards the first cleavage
      plane, in contrast to the previous claims. Thus, there is no predetermined axis
      in the mouse egg. We also presented a novel model for specification of the first
      cleavage plane: this is defined as the plane separating the two apposing
      pronuclei that have moved to the center of the egg. In this review we will
      elucidate the discrepancy between the previous model and our model, and discuss
      the possible causes.

PMID- 15846074
TI  - Signal therapy of NF1-deficient tumor xenograft in mice by the anti-PAK1 drug
      FK228.
AB  - PAK1, a Rac/CDC42-dependent Ser/Thr kinase, is required for the malignant growth
      of RAS transformants as well as both NF1-deficient and NF2-deficient cancer
      cells. FK228, a histone deacetylase (HDAC) inhibitor, suppresses the growth of
      more than 70% of human cancers in vivo including RAS transformants, breast
      cancers and prostate cancers by activating a set of genes including the tumor
      suppressors gelsolin and p21(WAF1), that block upstream and downstream of PAK1,
      respectively. Here we demonstrate that (1) the anti-PAK1 drug FK228 (0.1 nM)
      completely blocks the growth of both NF1-deficient and NF2-deficient cancer cells
      in vitro, and that (2) FK228 (2.5 mg/kg, i.p., twice a week) causes the complete
      regression of an NF1-deficient human malignant peripheral nerve sheath tumor
      (MPNST) xenograft in nude mice. This is the very first case where a chemical drug
      in clinical trials for cancers has ever worked so effectively on
      neurofibromatosis (experimental neurofibromas) in vivo.

PMID- 15846075
TI  - Genomic instability in Gadd45a-/- cells is coupled with S-phase checkpoint
      defects.
AB  - Gadd45a is a p53-regulated gene whose protein product, like p53, is involved in
      maintenance of genome stability. Specifically, deletion of Gadd45a leads to
      extensive aneuploidy as a consequence of centrosome amplification and subsequent
      abnormal segregation of chromosomes during mitosis. S-phase checkpoints were
      investigated in Gadd45a(-/-) cells to determine possible defects contributing to
      the uncoupling of centrosome duplication and DNA replication. In the presence of
      hydroxyurea, Gadd45a(-/-) mouse embryo fibroblasts show increased centrosome
      amplification coupled with loss of a sustained S-phase checkpoint. Gadd45a
      deletion allows another form of genomic instability, gene amplification, when p21
      (Cdkn1a gene product) is deleted also. Gene amplification in Gadd45a(-/-)p21(-/-)
      cells correlated with loss of both G(1) and S-phase checkpoints. Multiple
      conditions of nutrient deprivation failed to prevent DNA synthesis in Gadd45a(-/
      ) cells. Gadd45a is therefore required for proper S-phase control and checkpoints
      under multiple conditions of nutrient deprivation. It is proposed that loss of S
      phase control may account for both the uncoupling of DNA replication and
      centrosome duplication, and conferring gene amplification proficiency in cells
      lacking Gadd45a(-/-). This is of particular importance for solid tumors, which
      may lack sufficient nutrients yet are unable to elicit checkpoints preventing
      genomic instability under these conditions.

PMID- 15846076
TI  - Restaging the spindle assembly checkpoint in female mammalian meiosis I.
AB  - In mammalian somatic cells, the spindle assembly checkpoint (SAC) is
      indispensable for ensuring the fidelity of chromosome segregation by delaying
      cell-cycle progression in the face of even a single misaligned chromosome. In
      contrast, the role of the SAC in unperturbed mammalian oocytes is less well
      defined as progression through meiosis I is unaltered in mouse oocytes in the
      presence of one or a few misaligned chromosomes. Furthermore, attempts to disable
      the function of the SAC protein, Mad2, in mouse oocytes have produced conflicting
      results. To gain further insight into SAC function during female mammalian
      meiosis I, we recently utilised a morpholino-based antisense approach to deplete
      the majority of Mad2 in mouse oocytes. Our results define a clear role for Mad2
      in ensuring the proper timing of meiosis I events and ultimately, in ensuring the
      fidelity of homologue disjunction. We discuss the implications of these results
      for the regulation of meiosis I in mammalian oocytes and for the genesis of human
      aneuploidy.

PMID- 15846077
TI  - Analysis of the Bcl-2 and p53 protein expression in the lymphoproliferative
      lesions in the upper Egypt.
AB  - BACKGROUND: Lymphomagenesis involves poorly understood alterations in the
      proapoptotic and prosurvival molecules. In the Upper Egypt, the clinicopathologic
      and genetic characteristics (p53 and Bcl-2) of the lymphoproliferative lesions
      (reactive hyperplasia, RH; Non-Hodgkin's lymphoma, NHL and Hodgkin's disease, HD)
      is unknown. OBJECTIVES: To examine the lymphoproliferative lesions for: (1) their
      clinicopathologic features, (2) the p53, and Bcl-2 protein expression and (3) the
      correlation between the clinicopathologic features and the genetic alterations.
      METHODS: p53 and Bcl-2 protein expression was immunohistochemically evaluated in
      68 lesions including 47 NHL, 10 HD, and 11 RH. The average weighted scores
      reflecting staining intensity and the percentage of positive cells were
      calculated. RESULTS: Clinically: 1) the mean age incidence gradually increased
      from HD to RH to NHL (16.1 +/- 5.9, 36.6 +/- 7.45 and 46.74 +/- 3.2, p = 0.001)
      and 2) NHL and RH showed slight female (1.1:1) and male (1.2:1) sex predilection,
      respectively. Also, HD has male (2.3:1) sex predilection. The bcl-2 average
      weighted scores showed gradual downregulation with the transition from low to
      intermediate to high grade NHL (9.50 +/- 1.12 > 6.67 +/- 0.70 > 6.28 +/- 0.83, p
      = 0.041). Alternatively, the p53 average weighted scores showed gradual
      upregulation with the transition from low to intermediate to high grade NHL (0.40
      +/- 0.22 < 1.72 +/- 0.35 < 2.15 +/- 0.52, p = 0.023). There was a negative
      correlation between bcl-2 and p53 protein expression in NHL (r = -0.221, p =
      0.165). In HD, Reed-Sternberg cells and their variants showed positive and
      negative reactivity for Bcl-2 and p53 protein expression, respectively.
      CONCLUSIONS: In the Upper Egypt: (1) lymphoproliferative lesions had some
      peculiar clinicopathologic features and (2) Bcl-2 and p53 proteins are altered in
      the lymphoproliferative lesions.

PMID- 15846078
TI  - Aberrant laminin beta3 isoforms downstream of EWS-ETS fusion genes in Ewing
      family tumors.
AB  - Ewing family tumors (EFTs) are associated with a chromosomal translocation
      resulting in a fusion of the amino-terminus of EWS with the DNA-binding domain of
      an ETS transcription factor. Although previous reports suggested that these
      chimeric proteins would act as aberrant transcription factors, their downstream
      targets have not been fully elucidated. To identify downstream targets of these
      EWS-ETS fusion proteins, we introduced EWS-ETS fusion constructs into a human
      fibrosarcoma cell line, HT-1080, by retroviral transduction. Here we report that
      the LAMB3 gene encoding the beta3 chain of basement membrane protein laminin-5 is
      induced to a significantly higher level in cells expressing EWS-ETSs than in
      cells expressing normal ETSs. Additionally through use of an antisense
      oligonucleotide for EWS-ERG in the W-ES EFT cell line, laminin beta3 protein was
      reduced coordinately with EWS-ERG fusion protein expression. Furthermore, we
      found small mRNAs were preferentially transcribed from the LAMB3 gene in EFT cell
      lines. Molecular cloning of the entire coding region shows that the alternative
      transcripts from different promoter(s) located within the intron 14, which encode
      small proteins, likely are major products of the LAMB3 gene in EFT cells. We show
      that the small isoforms conferred increased anchorage-independent proliferation
      to NIH3T3 cells. Together with previous studies showing that laminin-5 is
      involved in the invasive and malignant phenotype of several tumor types, our data
      suggest that the oncogenic effect of EWS-ETS may be mediated in part by
      upregulation of LAMB3 expression.

PMID- 15846079
TI  - Targeting TGFbeta signaling for cancer therapy.
AB  - Transforming growth factor (TGF) betas are multifunctional polypeptides that
      regulate several cellular functions, including cell growth and differentiation,
      extra cellular matrix production, motility and immunosuppression. The growth
      inhibiting properties of TGFbeta have gained much attention into its role as a
      tumor suppressor. There is, however, now increasing evidence that TGFbeta
      switches roles, from tumor suppressor to tumor promoter, as the tumor progresses.
      Given the integral role of TGFbeta in the tumor progression, it follows that
      TGFbeta signaling offers an attractive target for cancer therapy. Several
      strategies including the use of antisense oligonucleotides for TGFbeta, TGFbeta
      antibodies, dominant negative TGFbeta receptor II, and small drug-molecules to
      inhibit TGFbeta receptor I kinase have shown great promise in the preclinical
      studies. These new findings, coupled with progressing clinical trials indicate
      that inhibition of TGFbeta signaling may, indeed, be a viable option to cancer
      therapy. This review summarizes the TGFbeta signaling, the dual role of TGFbeta-
      as a tumor suppressor and tumor promoter, and various strategies targeted against
      TGFbeta signaling for cancer therapy. The next few years promise to better our
      understanding of approaching cancer therapy with an eye to the inhibition of
      TGFbeta signaling.

PMID- 15846080
TI  - Activation of Bax by BH3 domains during apoptosis: the unfolding of a deadly
      plot.
AB  - The BH3-only proteins are intracellular death ligands that are critical for
      initiating apoptosis. Their mode of action is dependent upon the ability of their
      BH3 domain to interact with pro- and anti-apoptotic multi-domain members of the
      Bcl-2 family. Direct agonists of the pro-apoptotic multi-domain protein Bax, and
      other BH3-only proteins, induce Bax activation and apoptosis by independent, yet
      cooperative, pathways.

PMID- 15846081
TI  - Dimethyl-celecoxib (DMC), a derivative of celecoxib that lacks cyclooxygenase-2
      inhibitory function, potently mimics the anti-tumor effects of celecoxib on
      Burkitt's lymphoma in vitro and in vivo.
AB  - The nonsteroidal anti-inflammatory drug (NSAID) celecoxib is a selective
      cyclooxygenase-2 (COX-2) inhibitor that has shown some promising results as an
      anti-cancer drug. However, the question arose as to whether or not its COX-2
      inhibitory function is required for its anti-tumorigenic properties. We therefore
      employed dimethyl-celecoxib (DMC), which is a close structural analog of
      celecoxib that lacks COX-2-inhibitory function, to investigate this question. By
      performing a combination of in vitro and in vivo studies with Burkitt's lymphoma
      cells, we found that DMC potently mimics all of the anti-proliferative and anti
      tumorigenic effects of celecoxib. In cell culture, DMC effectively inhibits cell
      proliferation through the down-regulation of cyclins A and B and the ensuing loss
      of cyclin-dependent kinase activity. This effect appears to take place in vivo as
      well and results in significantly (p<.002) reduced tumor growth in experimental
      animals. Thus, our results demonstrate that the anti-proliferative and anti
      tumorigenic properties of celecoxib and DMC are indistinguishable, at least in
      Burkitt's lymphoma cells, and therefore, that the COX-2-inhibitory function is
      not required for these effects.

PMID- 15846082
TI  - An optimized conditional suicide switch using doxycycline-dependent expression of
      human tBid.
AB  - We have examined in a HeLa model system whether tight doxycycline-dependent
      expression of human tBid can be used as a fast and efficient suicide switch. A
      stably transfected cell line expressing human tBid in a strictly dox-dependent
      manner showed fast and efficient killing with up to 98 % specific cell death 24 h
      after induction. The survival rate was only 0.6 % after eleven days of dox
      treatment. Very low amounts of tBid were sufficient to induce apoptosis
      indicating that stringent control of the dox-dependent suicide gene is essential
      for cell survival in the absence of inducer. Using human tBid, an endogenous
      effector protein with low immunogenic potential, and doxycycline, an inducer with
      low cytotoxicity and a long record of safe use in humans, this conditional
      suicide switch provides a tool for various applications, e.g., adoptive immune
      transfer.

PMID- 15846083
TI  - p53 gain-of-function: tumor biology and bioinformatics come together.
AB  - p53 is typically viewed as a tumor suppressor. However, many missense somatic and
      germline mutations in the p53 gene cause gain-of-function whereby p53 acquires
      novel biochemical activities, such as the ability to transactivate transcription
      of new genes or to mediate new regulatory protein-protein interactions. Several
      recent studies show that at least some gain-of-function mutations of p53 are
      biologically relevant leading to a change in the tumor phenotype. Independent
      bioinformatic analysis of somatic mutation spectra of the p53 gene yields three
      lines of evidence supporting the notion that gain-of-function could be the
      prevalent mode of p53 evolution in tumors. (1) The hotspots in the p53 gene show
      signs of intensive positive selection. (2) The hotspots are located primarily in
      functionally important motifs of the DNA-binding domain of p53 which are highly
      conserved in interspecies evolution. (3) The spectra of hotspots significantly
      differ among various tumor types and the germline (Li-Fraumeni syndrome); in
      addition to the hotspots shared by the germline and some of the tumors, many are
      tumor-specific. The latter observation suggests an unexpected level of complexity
      of p53 evolution in tumors, with distinct novel function gained in different
      tumors.

PMID- 15846084
TI  - Prostate specific antigen as a clinical biomarker for prostate cancer: what's the
      take home message?
AB  - Prostate specific antigen (PSA) continues to be challenged as a legitimate
      clinical biomarker in early detection of prostate cancer due to lack of
      specificity for malignant transformation. Skepticism surrounding the utility of
      serum PSA as a clinical marker is not new and many questioned its initial use in
      widespread prostate cancer screening due to non-specific expression and low
      predictive value for cancer detection. Despite these initial concerns, serum PSA
      measurement along with digital rectal examination (DRE) is currently the accepted
      practice for prostate cancer screening in the United States with hundreds of
      thousands of men undergoing serum PSA measurement annually. In contrast to its
      role for early detection, serum PSA measurement as a surrogate for prostate
      cancer recurrence (biochemical failure) following curative intent therapy has
      consummate clinical utility in post-treatment surveillance. As thousands of men
      each year are aggressively treated for potentially curable prostate cancer,
      development of simple and effective diagnostic tools for detecting treatment
      failures should be an important area of biomedical and clinical investigation. We
      have constructed and tested a home-based prostate cancer surveillance device for
      use by patients to detect PSA from blood obtained by finger stick. Our initial
      results suggest that home based PSA testing is feasible and may have clinical
      utility in management of men treated for prostate cancer.

PMID- 15846085
TI  - Proliferation and polarity in breast cancer: untying the Gordian knot.
AB  - Epithelial cancers are associated with genomic instability and alterations in
      signaling pathways that affect proliferation, apoptosis, and integrity of tissue
      structure. Overexpression of a number of oncogenic protein kinases has been shown
      to malignantly transform cells in culture and to cause tumors in vivo, but the
      interconnected signaling events induced by transformation still awaits detailed
      dissection. We propose that the network of cellular signaling pathways can be
      classified into functionally distinct branches, and that these pathways are
      rewired in transformed cells and tissues after they lose tissue-specific
      architecture to favor tumor expansion and invasion. Using three-dimensional (3D)
      culture systems, we recently demonstrated that polarity and proliferation of
      human mammary epithelial cancer cells were separable consequences of signaling
      pathways downstream of PI3 kinase. These, and results from a number of other
      laboratories are beginning to provide insight into how different signaling
      pathways may become interconnected in normal tissues to allow homeostasis, and
      how they are disrupted during malignant progression.

PMID- 15846086
TI  - Achieving hypoxia-inducible gene expression in tumors.
AB  - Hypoxia is an inevitable feature of solid tumors and a common cause of treatment
      failure. Hypoxia acts as a trigger to genetic instability, apoptosis and possibly
      metastases. The adaptive response to cellular hypoxia involves the modulation of
      the synthesis of multiple proteins controlling processes such as glucose
      homeostasis, angiogenesis, vascular permeability and inflammation. The hypoxia
      responsive element (HRE) sequences isolated from oxygen-responsive genes have
      been shown to selectively induce gene expression in response to hypoxia when
      placed upstream of a promoter. The levels of induced gene expression were
      dependent on the number of HRE copies and the oxygen tension. Hypoxia-mediated
      cancer gene therapy strategies may represent a promising mean to significantly
      improve the efficacy of standard radiation therapy and chemotherapy approaches.

PMID- 15846087
TI  - The tumor suppressor protein p53 functions similarly to p63 and p73 in activating
      transcription in vitro.
AB  - The p53 tumor suppressor protein functions via specific gene activation to
      inhibit passage through the cell cycle and to trigger apoptosis. The p53 protein
      is homologous to p63 and p73, proteins that regulate transcription via the same
      promoter sequences but which activate different genes. In this study we tested
      whether p53, p63, and p73 have different mechanisms of activating transcription
      and if such a difference could explain how each factor stimulates the
      transcription of distinct sets of genes. We found that when comparing p53 to the
      transcriptional activator, GAL4-VP16, both of which are classified as acidic
      activators, that stimulation of transcription by p53 is dependent upon low Mg2+
      concentrations and limiting amounts of extract. By comparison, the stimulation of
      RNA synthesis by GAL4-VP16 was not dependent on a specific concentration of Mg2+
      but did require higher amounts of extract, suggesting that a certain factor not
      required for p53-dependent gene activation was limiting in the extract. In
      contrast to the differences between p53 and GAL4-VP16, p63 and p73 both regulated
      transcription in vitro under similar conditions as did p53. All three proteins,
      purified to near homogeneity, were equally active in binding to the p53-response
      element, and equally active in stimulating transcription reactions using naked
      DNA templates, DNA templates reconstituted in chromatin using histones purified
      from HeLa cells, or hyper-acetylated histones. These results argue that the gene
      specificity of p63 and p73 dependent activation of transcription depends upon
      specific coactivators present in the specific cell types and upon other factors
      bound to the promoters.

PMID- 15846088
TI  - Inhibition of p53 by lentiviral mediated shRNA abrogates G1 arrest and apoptosis
      in retinal pigmented epithelial cell line.
AB  - We silenced p53 gene expression in ARPE-19, a human retinal pigmented epithelial
      cell line using RNA interference. The effect of silencing the p53 gene in
      proliferating ARPE-19 cells was studied. Four short hairpin RNAs (shRNAs)
      targeting different regions of human p53 mRNA were delivered individually into
      ARPE-19 cells using lentiviral vector to produce stable cell lines. p53 mRNA and
      protein levels were reduced to varying extents in the four shRNA-transduced ARPE
      19 cell lines. The cell line that showed greatest reduction (85-90%) of p53
      expression showed decreased p21 promoter activation after DNA damage with
      camptothecin, etoposide and MMS. Whereas treatment of wild type ARPE-19 cells
      with camptothecin resulted in apoptosis, silencing p53 expression increased their
      survival. Cell cycle analyses indicated that irradiation resulted in a G(1)
      arrest in ARPE-19 cells, and that the arrest was significantly reduced in p53
      silenced cells. Thus, p53 plays a central role in the response of ARPE-19 cells
      to DNA damaging agents that act via different mechanisms. Additionally, ARPE-19
      cells with reduced p53 expression behave similar to tumor cell lines with mutated
      or non-functional p53. The present data demonstrate the utility of lentiviral
      vectors to create stable isogenic cell lines with reduced expression of a
      specific gene, thereby permitting the study of the function of a gene, the
      pathways controlled by it, and the effect of therapeutics on a cell with altered
      genetic makeup in a pair-wise fashion.

PMID- 15846090
TI  - A DNA repeat, NBL2, is hypermethylated in some cancers but hypomethylated in
      others.
AB  - Hypermethylation at certain CpG-rich promoters and hypomethylation at repeated
      DNA sequences are very frequently found in cancers. We provide the first report
      that a DNA sequence (NBL2) can be either extensively hypermethylated or
      hypomethylated in cancer. Previously, it was shown that NBL2, a complex tandem
      DNA repeat in the acrocentric chromosomes, is hypomethylated at NotI sites in
      >70% of neuroblastomas and hepatocellular carcinomas and in cells from ICF
      syndrome (DNMT3B-deficiency) patients. Unexpectedly, by Southern blot analysis of
      18 ovarian carcinomas, 51 Wilms tumors, and various somatic control tissues, we
      found that >70% of the cancers exhibited large increases in methylation at HhaI
      sites in NBL2 compared with all the controls. In contrast, 17% of the carcinomas
      showed major decreases in methylation at HhaI and NotI sites. The intermediate
      levels of methylation at HhaI sites in somatic controls enabled this discovery of
      cancer-linked hypermethylation and hypomethylation in NBL2. In a comparison of
      ovarian epithelial carcinomas, low malignant potential tumors, and cystadenomas,
      NBL2 hypermethylation at HhaI sites was significantly related to the degree of
      malignancy, and hypomethylation was seen only in the carcinomas. By RT-PCR, we
      found NBL2 transcripts at low levels in a few cancers and undetectable in various
      normal tissues. In the tumors there was no association of NBL2 hypomethylation
      and transcription, but this may reflect NBL2's lack of identifiable promoter
      elements and our evidence for run-through transcription from adjacent sequences
      into NBL2. The propensity of NBL2 sequences to become either hypermethylated or
      hypomethylated in cancer suggests that these opposite epigenetic changes share an
      early step during carcinogenesis and that cancer-linked hypermethylation might be
      spontaneously reversible.

PMID- 15846091
TI  - Indirect effects of Bax and Bak initiate the mitochondrial alterations that lead
      to cytochrome c release during arsenic trioxide-induced apoptosis.
AB  - Arsenic trioxide is a potent chemotherapeutic agent by virtue of its ability to
      selectively trigger apoptosis in tumor cells. Previous studies have demonstrated
      that arsenicals cause direct damage to mitochondria, but it is not clear that
      these effects initiate apoptosis. Here we used Bak-/- mouse liver mitochondria
      and virally immortalized Bax-/- Bak-/- mouse embryonic fibroblasts (MEFs) to
      investigate whether or not multidomain proapoptotic BCL-2 family proteins were
      required for arsenic-induced mitochondrial damage and cell death. At clinically
      achievable concentrations, arsenic stimulated cytochrome c release and apoptosis
      via a Bax/Bak-dependent mechanism. At higher concentrations (125 microM-1 mM),
      cells died via a Bax/Bak-independent mechanism mediated by oxidative stress that
      resulted in necrosis. Consistent with previous reports, arsenic directly
      inhibited complex I of the mitochondrial electron transport chain, which resulted
      in mitochondrial permeability transition (MPT), accompanying generation of
      reactive oxygen species (ROS), and thiol oxidation. However, these effects only
      occurred at concentrations of arsenic trioxide of 50 microM and higher, and the
      oxidative stress associated with these effects blocked caspase activation. Our
      data demonstrate for the first time that the cytochrome c release which initiates
      apoptosis in cells exposed to this classic mitochondrial poison occurs indirectly
      via the activation of Bax/Bak rather than via direct mitochondrial damage.
      Furthermore, the results implicate reactive oxygen species in a concentration
      dependent mechanistic switch between apoptosis and necrosis.

PMID- 15846092
TI  - Growth inhibition of head and neck squamous carcinoma cells by small interfering
      RNAs targeting eIF4E or cyclin D1 alone or combined with cisplatin.
AB  - Head and neck squamous cell carcinomas (HNSCCs) exhibit an increased expression
      of the translation initiation factor eIF4E and the cell-cycle regulator cyclin D1
      (CCND1). Both stimulate cell cycle progression and transform squamous epithelial
      cells. We used small interfering RNAs (siRNAs) to silence the expression of eIF4E
      and CCND1 in HNSCC UMSCC22B cells and analyzed the effects of reduced levels of
      these proteins on colony formation. Transfection of either eIF4E or CCND1 siRNAs
      decreased the levels of their targeted proteins and inhibited cell growth. siRNA
      mediated decrease of eIF4E has led to decreases in the expression of CCND1, basic
      fibroblast growth factor and vascular endothelial growth factor. Combination of
      these siRNAs and cisplatin showed more than additive inhibition of colony
      formation. These findings demonstrate that siRNA silencing of either eIF4E or
      CCND1 leads to inhibition of the growth of HNSCC cells and suggest that these
      siRNAs alone or combined with conventional cytotoxic agents may be useful for
      therapy of HNSCCs.

PMID- 15846093
TI  - Inhibitors of histone deacetylases alter kinetochore assembly by disrupting
      pericentromeric heterochromatin.
AB  - The kinetochore, a multi-protein complex assembled on centromeric chromatin in
      mitosis, is essential for sister chromosome segregation. We show here that
      inhibition of histone deacetylation blocks mitotic progression at prometaphase in
      two human tumor cell lines by interfering with kinetochore assembly. Decreased
      amounts of hBUB1, CENP-F and the motor protein CENP-E were present on
      kinetochores of treated cells. These kinetochores failed to nucleate and
      inefficiently captured microtubules, resulting in activation of the mitotic
      checkpoint. Addition of histone deacetylase inhibitors prior to the end of S
      phase resulted in decreased HP1-beta on pericentromeric heterochromatin in S
      phase and G(2), decreased pericentromeric targeting of Aurora B kinase, resulting
      in decreased premitotic phosphorylation of pericentromeric histone H3(S10) in
      G(2), followed by assembly of deficient kinetochores in M-phase. HP1-beta, Aurora
      B and the affected kinetochore proteins all were present at normal levels in
      treated cells; thus, effects of the inhibitors on mitotic progression do not seem
      to reflect changes in gene expression. In vitro kinase activity of Aurora B
      isolated from treated cells was unaffected. We propose that the increased
      presence in pericentromeric heterochromatin of histone H3 acetylated at K9 is
      responsible for the mitotic defects resulting from inhibition of histone
      deacetylation.

PMID- 15846094
TI  - Mitochondrial hexokinases: guardians of the mitochondria.
AB  - There is accumulating evidence that cell survival and energy metabolism are
      inexorably linked. As a major mediator of both the metabolic and anti-apoptotic
      effects of growth factors, the serine/threonine kinase Akt (also known as protein
      kinase B or PKB) is particularly well-suited to coordinate the regulation of
      these interrelated processes. Recent demonstrations that growth factors and Akt
      require glucose (Glc) to prevent apoptosis and promote cell survival are
      compatible with this contention, as is a positive correlation between Akt
      regulated mitochondrial hexokinase (mtHK) association and apoptotic resistance.
      From a phylogenetic perspective, the ability of Akt to regulate cellular energy
      metabolism apparently preceded the capacity to control cell survival, suggesting
      an evolutionary basis for the Glc dependent anti-apoptotic effects of Akt. We
      speculate that, somewhere in the course of evolution, the metabolic regulatory
      function of Akt evolved into an adaptive sensing system involving mtHK that
      ensures mitochondrial homeostasis, thereby coupling metabolism to cell survival.
      We also propose that this "guardian" function of mtHK may be specifically
      exploited for therapeutic purposes.

PMID- 15846095
TI  - Tumor profiling turmoil.
AB  - Tumor profiling aims to determine gene expression signatures that can
      discriminate between different sub-types of tumors. We have recently discovered a
      signature that can reliably detect which primary head-neck tumors have
      metastasized to local lymph nodes. This signature has great potential for
      clinical application and also offers unique insights into how metastasis occurs.
      Despite these obvious advances, discussed here alongside several other findings,
      such tumor profiling studies are currently receiving harsh criticism. We make
      clear that such evaluations can themselves also be critically evaluated. The
      separation between the two factions actually shows that it is too early to either
      dismiss or exalt tumor profiling studies. Final judgment requires waiting for the
      results of larger prospective studies carried out in parallel with current
      clinical practice.

PMID- 15846096
TI  - Targeting cancer cells by exploiting karyotypic complexity and chromosomal
      instability.
AB  - Multiple karyotypic abnormalities and chromosomal instability are particular
      hallmarks of many cancers that are relatively resistant to long term control by
      current chemotherapeutic agents. We have asked whether these same hallmarks,
      karyotypic complexity and instability, can be used as determinants for the
      screening of potential anticancer compounds. Using a panel of well characterized
      cancer cell lines we have been able to identify specific groups of chemical
      compounds that are more cytotoxic toward the relatively more karyotypically
      complex and unstable panel members. Thus, we delineate an approach for the
      identification of "lead compounds" for anticancer drug discovery complementary to
      approaches that are focused at the outset on a given gene or pathway.

PMID- 15846097
TI  - How disruption of cell cycle regulating genes might predispose to sun-induced
      skin cancer.
AB  - The Ink4a/Arf (CDKN2a) locus encodes two proteins that regulate two of the most
      important tumor suppressor pathways represented by p53 and Rb.(1) Loss of either
      p16(INK4a) or p19(ARF) was recently reported to reduce the ability of mouse cells
      to repair UV-induced DNA damage and to induce a UV-mutator phenotype. This
      observation was independent of cell cycle effects incurred by either p16(INK4a)
      and/or p19(ARF) loss, as it was demonstrable in unirradiated cells using UV
      treated DNA. We suggest that this might explain why germ line mutations of
      INK4a/ARF predispose mainly to malignant melanoma, a UV-induced skin cancer, and
      provides a molecular explanation for the link between melanomagenesis and
      impaired DNA repair. It also further demonstrates that regulation of cell cycle
      check points and DNA repair in response to genomic insults, such as ultraviolet
      irradiation are intricately interwoven processes. Differences in the apoptotic
      response to ultraviolet light between melanocytes and keratinocytes might explain
      why INK4a/ARF mutations predispose to malignant melanoma, but not to keratinocyte
      derived skin cancers.

PMID- 15846098
TI  - The potent inhibitory effects of cisapride, a specific blocker for human ether-a
      go-go-related gene (HERG) channel, on gastric cancer cells.
AB  - BACKGROUND: Ion channels may play a role in carcinogenesis. Human ether-a-go-go
      related gene (HERG) encoding one of the components of delayed rectifier potassium
      currents has been indicated to be involved in tumor cell growth and death. Our
      aim is to investigate the effects of cisapride, a specific blocker for HERG
      channel, on human gastric cancer cells. METHODS: The effects of cisapride on the
      proliferation, clonogenicity, cell cycle and apoptosis of gastric cancer cells
      were evaluated by MTT assay, clonogenicity assay, flow cytometry and transmission
      electron microscopy. The expression of HERG mRNA and protein in gastric cancer
      cells and tissues was measured by RT-PCR, Western blot and immunohistochemistry,
      respectively. RESULTS: HERG mRNA and protein were exclusively expressed in
      gastric cancer cells. The HERG protein was localized in the cytoplasm and
      membrane of the gastric cancer cells. The proliferation of gastric cancer cells
      expressing HERG protein was inhibited in a time- and dose-dependent manner when
      treated with cisapride (P<0.05). The clonogenicity of gastric cancer cells
      treated with cisapride (100 nM) was reduced (P<0.05). Flow cytometric analysis
      indicated that cisapride tends to inhibit gastric cancer cells entering S phase
      from G(1) phase in the cell cycle (P<0.05). Apoptotic cells were found increased
      in gastric cancer cells treated with cisapride by both flow cytometry and
      electron microscopy. CONCLUSIONS: As HERG channel blocker, cisapride, can inhibit
      the growth of gastric cancer cells by altering distribution of cell cycle and
      inducing apoptosis so as to be of potential value in the treatment of gastric
      cancer.

PMID- 15846099
TI  - Decreased glycolytic metabolism accelerates apoptosis in response to 2-acetyl
      furanonaphthoquinone in K1735 melanoma irrespective of bcl-2 overexpression.
AB  - Solid tumors are often placed under stress conditions, such as glucose starvation
      which may result in topoisomerase II drug resistance. In this study, we
      investigated whether glucose deprivation or substitution by fructose regulates
      tumor cell apoptosis induced by 2-acetyl furanonaphthoquinone (FNQ). We now show
      that FNQ exerts much greater antitumor activity than either 7-methoxy 2-ethyl FNQ
      or 2-ethyl FNQ. Whereas 0.8 microM FNQ induces apoptosis after 16 hours in
      glucose-supplemented conditions irrespective of bcl-2 overexpression in K1735
      melanoma, 0.5 microM FNQ is also effective within 12 hours in low glucose or in
      fructose-supplemented medium. Under the latter conditions, apoptosis-associated
      PARP cleavage and cytosolic cytochrome C are increased, together with induction
      and partial translocation to mitochondria of phosphorylated Jun-N-terminal kinase
      and massive upregulation of mitochondrial Mn superoxide dismutase. We propose
      that mitochondrial colocalization of these activities is important in this
      synergistic anti-tumor effect of FNQ and glucose depletion. Since glucose
      limitation slows proliferation and decreases efficacy of some genotoxic drugs
      that trigger apoptosis in rapidly dividing cells, we propose evaluating FNQ as a
      novel therapeutic anti-cancer adjuvant against slowly proliferating tumors.

PMID- 15846100
TI  - Enhanced growth inhibition and apoptosis induction in NSCLC cell lines by
      combination of celecoxib and 4HPR at clinically relevant concentrations.
AB  - Celecoxib exhibits cancer preventive and therapeutic effects in animal models and
      clinical trials. It presumably acts through selective inhibition of
      cyclooxygenase-2 (COX-2) and subsequent reduction of prostaglandin (PG)
      synthesis. However, the concentrations of celecoxib required for growth
      inhibition and apoptosis induction in vitro are higher than those needed for
      suppression of PGs. Moreover, those concentrations are not achievable in humans
      raising a controversy regarding the clinical relevance of in vitro data. We
      investigated the activity of celecoxib alone and in combination with the pro
      apoptotic retinoid N-(4-hydroxyphenyl)retinamide (4HPR) on growth and apoptosis
      of human nonsmall cell lung cancer (NSCLC) cell lines. Celecoxib inhibited growth
      of thirteen NSCLC cell lines with IC50 values ranging from 19 to 33 microM
      regardless of their COX-2 expression. Apoptosis was induced in cells with high
      (A549) as well as low (H1792) COX-2 levels but only at a concentration of 75
      microM celecoxib. However, treatment with pharmacologically feasible
      concentrations of celecoxib (< or = 10 microM) in combination with 4HPR (< or = 2
      microM) resulted in a marked suppression of NSCLC cell growth and colony
      formation. Apoptosis mediated by activation of caspase-3, cleavage of PARP and
      lamin A was suppressed by addition of antioxidants, suggesting that the
      generation of reactive oxygen species was partially involved. This study
      indicates, that celecoxib combined with 4HPR is more effective than treatment
      with either agent alone in inhibition of growth and induction of apoptosis in
      NSCLC cells. It suggests further investigations of this combination for lung
      cancer treatment.

PMID- 15846101
TI  - Trichostatin A (TSA) sensitizes the human prostatic cancer cell line DU145 to
      death receptor ligands treatment.
AB  - The human prostatic carcinoma cell line DU145 has previously been found to be
      resistant to treatment with TNF-family ligands. However, TRAIL, TNF-alpha and
      anti-Fas antibodies (Ab) treatment in combination with the histone deacetylase
      inhibitor Trichostatin A (TSA) converted the phenotype of DU145 from resistant to
      sensitive. TSA induced 15% cell death but simultaneous treatment with TRAIL, TNF
      alpha and anti-Fas Ab resulted in 55%, 70% and 40% cell death, respectively.
      Simultaneous treatment did not increase the level of TSA-induced histone
      acetylation, but induced the release of acetylated histones from chromatin into
      the cytosol. This release was caspase dependent since it was abrogated by Z-VAD
      fmk. In addition, treatment with TSA induced caspase-9 activation and resulted in
      the release of cytochrome c and Smac/DIABLO from mitochondria. To further
      investigate the role of caspase-9 in TSA-mediated apoptosis we used two different
      approaches: (1) cells were pretreated with the caspase-9 inhibitor Z-LEHD-fmk,
      and (2) cells were transfected with a dominant-negative form of caspase-9. Both
      approaches gave similar results: cells became resistant to treatment with TSA.
      These data indicate that TSA mediates its effect via the mitochondrial pathway.
      This was confirmed by examining DU145 overexpressing Bcl-2. These transfectants
      were resistant to TSA treatment. Taken together, our data shows that only
      simultaneous treatment with TNF-family ligands and TSA in DU145 resulted in
      caspase activity sufficient to induce apoptosis. The combination of TSA and TNF
      family ligands could potentially be the basis for the treatment of prostate
      cancer.

PMID- 15846102
TI  - Augmentation of antitumor effects of p53 gene therapy by combination with HDAC
      inhibitor.
AB  - We have previously shown that the HDAC inhibitors (HDACI) activate the p53
      molecule through acetylation of 320 and 373 lysine residues, upregulate PIG3 and
      NOXA and induce apoptosis in cancer cells expressing wild and pseudo-wild type
      p53 genes (Terui T, et al. Cancer Res 2003; 63:8948-54). It has also been
      reported that expression of the Coxsackie adenovirus receptor and subsequent
      transfection efficiency of the adenovirus in cancer cells were enhanced by HDACI
      treatment. In this study, we extended these observations to explore the
      combination effect of adenoviral vector carrying wild type p53 (Ad-p53) gene
      therapy with a HDACI, sodium butyrate (SB), on xenografted human gastric cancer
      cells (KATO-III) and hepatocellular carcinoma cells (HuH7) in nude mice. We first
      confirmed an increased expression of Coxsackie adenovirus receptors with an
      associated increment of transgene (X-gal) expression by SB treatment in KATO-III
      cells. We then injected Ad-p53 into subcutaneous tumors of KATO-III and HuH7
      combined with intraperitoneal administration of SB and found a significantly
      higher growth suppressive effect than single treatments of each. Even a complete
      regression of tumors was observed in three of five mice treated with this
      combination while with single treatment no tumor regression was observed. Tumors
      treated with the combination showed higher numbers of TUNEL positive cells than
      those treated with a single modality. Moreover, necrotic changes were more
      evident in tumors treated with the combination than separately, a compatible
      finding to the observation that vascularity revealed by CD34 staining was poorer
      in tumors treated with the combination than those treated with p53 gene or SB
      alone. This was further supported by the finding that BAI-1 (brain specific
      angiogenesis inhibitor-1), an inhibitor of vascularization, was induced by SB
      treatment in KATO-III and HuH7 cells transfected with Ad-p53. Thus SB was shown
      to be an efficient potentiator of p53 gene therapy for cancer.

PMID- 15846103
TI  - Recombination at mammalian telomeres: an alternative mechanism for telomere
      protection and elongation.
AB  - In human cells, homologous recombination (HR) provides an accurate mechanism for
      the repair of DNA double-strand breaks caused by replication fork breakdown or
      DNA damaging agents. HR also plays a role in the maintenance of eukaryotic
      telomeres; cells defective in the recombinational repair proteins RAD51D or RAD54
      exhibit telomere shortening and end-to-end chromosome fusions. Here we discuss
      the way in which HR contributes to telomere protection and elongation in
      mammalian cells. Understanding the mechanisms by which HR promotes telomere
      maintenance has important implications for genomic stability and tumorigenesis.

PMID- 15846104
TI  - Ultraviolet radiation induces phosphorylation and ubiquitin-mediated degradation
      of DeltaNp63alpha.
AB  - DeltaNp63alpha, a homologue of the tumor suppressor p53, acts as a
      transcriptional repressor with dominant negative effects towards p53.
      Additionally, DeltaNp63alpha is overexpressed in a number of squamous cell
      carcinomas, suggesting a potential role in oncogenesis. However, the mechanisms
      regulating p63 have yet to be elucidated. The goal of the current study was to
      determine the effect of various genotoxic stresses on DeltaNp63alpha
      posttranslational modification and stability in normal and transformed squamous
      epithelial cells. We found that DeltaNp63alpha protein levels decreased after
      ultraviolet radiation and paclitaxel treatment of both normal and transformed
      cells. After UV and paclitaxel treatment, DeltaNp63alpha phosphorylation was
      significantly modulated. Additionally, DeltaNp63alpha protein levels were
      regulated in a proteasome-dependent manner in control and UV treated cells with
      increased DeltaNp63alpha ubiquitination after UV treatment or proteasome
      inhibition. Our studies provide insight to a mechanism for DeltaNp63alpha
      regulation during normal cell proliferation and, in particular, after stress.
      Further, the inverse regulation of p53 and DeltaNp63alpha protein levels after
      cell stress through opposing regulation of proteasome-mediated degradation may
      allow for rapid transcriptional changes of specific target genes that are
      consistent with the roles of these family members in tumor suppression and cell
      growth.

PMID- 15846105
TI  - Met activation and receptor dimerization in cancer: a role for the Sema domain.
AB  - Ligand dependent activity of receptor tyrosine kinases is critical for modulating
      downstream signaling and cell proliferation. In normal cellular context,
      hepatocyte growth factor (HGF) regulates MET kinase activation and mediates cell
      proliferation, migration and motility. Recent elucidation of the MET
      extracellular domain suggests that the Sema domain, which bears structural
      similarity to other Semaphorins and Plexin family members, plays a critical role
      in ligand mediated receptor activation. Overexpression of MET which is observed
      in many cancers leads to ligand independent receptor dimerization and activation.
      Evidence to support a role for the Sema domain in cancer and therapeutic
      implications of targeting the Met Sema domain are discussed in this review.

PMID- 15846106
TI  - PWT-458, a novel pegylated-17-hydroxywortmannin, inhibits phosphatidylinositol 3
      kinase signaling and suppresses growth of solid tumors.
AB  - Deregulated phosphatidylinositol 3-kinase (PI3K) signaling pathway is widely
      implicated in tumor growth and resistance to chemotherapy. While a strong
      rationale exists for pharmacological targeting of PI3K, only a few proof-of
      principle in vivo efficacy studies are currently available. PWT-458, pegylated-17
      hydroxywortmannin, is a novel and highly potent inhibitor of PI3K in animal
      models. Upon in vivo cleavage of its poly(ethyleneglycol) (PEG), PWT-458 releases
      its active moiety 17-hydroxywortmannin (17-HWT), the most potent inhibitor in its
      class. Here we show that a single intravenous injection of PWT-458 rapidly
      inhibited PI3K signaling, as measured by a complete loss of AKT (Ser-473)
      phosphorylation in xenograft tumors grown in nude mice. Following a daily X5
      dosing regimen, PWT-458 demonstrated single-agent antitumor activity in nude
      mouse xenograft models of U87MG glioma, nonsmall cell lung cancer (NSCLC) A549,
      and renal cell carcinoma (RCC) A498. Efficacious doses ranged from 0.5 mg/kg to
      10 mg/kg, achieving a superior therapeutic index over 17-HWT. PWT-458 augmented
      anticancer efficacy of a suboptimal dose of paclitaxel against A549 and U87MG
      tumors. Combination treatment of PWT-458 and an mTOR inhibitor, Pegylated
      Rapamycin (Peg-Rapa), resulted in an enhanced antitumor efficacy in U87MG.
      Finally, PWT-458 in combination with interferon-alpha (Intron-A) caused a
      dramatic regression of RCC A498, which was not achieved by either agent alone.
      These studies identify PWT-458 as an effective anticancer agent and provide
      strong proof-of-principle for targeting the PI3K pathway as novel anticancer
      therapy.

PMID- 15846107
TI  - Regulation of vascular endothelial growth factor (VEGF) production and
      angiogenesis by tissue Factor (TF) in SGC-7901 gastric cancer cells.
AB  - Tissue factor (TF), an initiator of the extrinsic coagulation cascade, is
      expressed in a wide range of cancer cells and plays important roles in cancer
      progression and metastasis. We demonstrated between TF and vascular endothelial
      growth factor (VEGF) production differences in four human gastric cell lines. One
      of these cell lines, SGC-7901, a high TF and VEGF producer, was grown
      subcutaneously in severe combined immuno-deficient (SCID) mice. The SCID mice
      generated solid tumors characterized by intense vascularity. In contrast, SGC
      7901 cells transfected with antisense TF cDNA generated relatively avascular
      tumors in SCID mice, as determined by immunohistochemical staining of tumor
      vascular endothelial cells with anti-VIII factor antibody. To investigate the
      structure-function relationship between TF and VEGF, the SGC-7901 cell line was
      transfected with antisense a full-length TF cDNA, a cytoplasmic deletion mutant
      lacking the distal three serine residues (potential substrates for protein kinase
      C), or an extracellular domain mutant, which has markedly diminished function for
      activation of factor X. Cells transfected with the full-length antisense TF
      sequence produced decreased levels of both TF and VEGF. Transfectants with the
      extracellular domain mutant produced high levels of VEGF mRNA. However, cells
      transfected with the cytoplasmic deletion mutant construct produced increased
      levels of TF, but little or no VEGF. Thus, the cytoplasmic tail of TF may signal
      VEGF expression in some tumor cells.

PMID- 15846108
TI  - Enhancing TRAIL-induced apoptosis by Bcl-X(L) siRNA.
AB  - We previously found that a change in the balance between mitochondrial pro- and
      anti-apoptotic proteins caused by ectopic expression of the Bax gene led to
      increased induction of apoptosis by tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL). To investigate whether a similar effect can be elicited
      by down-regulating Bcl-X(L), an anti-apoptotic protein, we tested the effects of
      a small interfering RNA (siRNA) specific for Bcl-X(L) in TRAIL-resistant cells.
      The down-regulation of Bcl-X(L) by siRNA inhibited cell proliferation and
      sensitized TRAIL-induced apoptosis in human cancer cells with both acquired and
      intrinsic TRAIL resistance. Combining the Bcl-X(L) siRNA with TRAIL protein
      treatment resulted in an increase in the percentage of apoptotic cells and
      increased cleavage of caspase-8, caspase-9, caspase-3 and PARP. Furthermore, the
      release of cytochrome c but not Smac from mitochondria was induced by Bcl-X(L)
      siRNA alone, and this release was dramatically amplified by combining the Bcl
      X(L) siRNA and TRAIL protein treatment. Together, our data suggest that
      simultaneous triggering of the death receptor and mitochondrial apoptotic
      pathways leads to enhanced induction of apoptosis, which makes it potentially
      useful for the treatment of resistant cancers.

PMID- 15846111
TI  - A novel anti-pancreatic cancer agent, LY293111.
AB  - Arachidonic acid is metabolized by two major pathways, cyclooxygenases and
      lipoxygenases. The metabolites catalyzed by these enzymes are important mediators
      of acute and chronic inflammation. Both enzymes and their metabolites are well
      recognized to be involved in cancer development and progress. It is well
      documented that inhibition of cyclooxygenase 2 (COX-2) activity decreases cancer
      incidence and inhibits tumor growth. It has also been reported that 5
      lipoxygenase is involved in cancer cell survival and proliferation. 5
      lipoxygenase metabolites including both 5-HETE and leukotriene (LT) B4 directly
      mediate cancer cell growth. Although 5-HETE receptors are still elusive, two LTB4
      receptor subtypes (BLT1 and BLT2) have been characterized. Both 5-lipoxygenase
      and LTB4 receptors are upregulated in both pancreatic cancer and early pancreatic
      cancer lesions; hence, these proteins are potential targets for cancer treatment
      and prevention. Recent studies have shown that an orally stable leukotriene (LT)
      B4 receptor antagonist, LY293111, has a potent anti-pancreatic cancer effect.
      LY293111 inhibits pancreatic cancer growth, induces tumor cell apoptosis both in
      vitro and in vivo, and enhances the anti-pancreatic cancer effect of gemcitabine.
      LY293111 exhibits its anti-cancer effects through LTB4 receptors and peroxisome
      proliferator activated receptor-gamma. A phase I clinical trial indicated that
      LY293111 is well tolerated by patients with no significant side-effects. LY293111
      may be a valuable drug for treatment of pancreatic cancer, especially in
      combination with gemcitabine. A double-blinded, placebo-controlled phase II
      clinical trial with LY293111 is currently underway. This review summarizes the
      current research status of LY293111 as an anti-cancer agent with a focus on
      pancreatic cancer.

PMID- 15846112
TI  - Proteasome: an emerging target for cancer therapy.
AB  - Proteasome inhibitors represent novel anti-cancer drugs which interact with the
      proteasome-ubiquitin pathway. The 26S proteasome is a multicatalytic threonine
      protease with three distinct catalytic activities. It is responsible for
      intracellular protein turnover in eukaryotic cells, including the processing and
      degradation of short- and some long-living proteins required for regulation of
      various cellular functions. Subsequently, the inhibition of the proteasomal
      function results in stabilization and accumulation of its substrates, which
      notably include cyclins, cyclin-dependent kinase inhibitors, transcriptional
      factors, tumor suppressor proteins and proto-oncogenes. This results in
      confounding signals in the cell inducing cell cycle arrest and activation of
      apoptotic programs. Acting on transcriptional factor NF-kappaB, which is
      upregulated in some tumors undergoing chemotherapy or irradiation and
      downregulated by proteasome inhibition, a significant chemosensitization and
      consequently synergistic effects concerning the anti-tumor activity could be
      achieved. Bortezomib is the first proteasome inhibitor that has entered clinical
      trials. In multiple myeloma, both the US Food and Drug Administration and
      European Medicine Evaluation Agency granted approval for the use of bortezomib
      (Velcade) for the treatment of multiple myeloma patients who have received at
      least two prior therapies and have demonstrated disease progression on the last
      therapy. At present, other trials examine the activity in a variety of solid
      tumors and hematological malignancies. This paper reviews preclinical and
      clinical results.

PMID- 15846113
TI  - Epidermal growth factor receptor and signal transduction: potential targets for
      anti-cancer therapy.
AB  - Agents targeting the epidermal growth factor receptor (EGFR) pathway hold
      particular promise for the treatment of patients with advanced disease, for whom
      standard chemotherapy is generally palliative. Expression of EGFR on numerous
      types of solid tumors, and the association of EGFR activation with tumorigenic
      processes including proliferation, anti-apoptosis and metastatic spread, make
      this pathway a particularly compelling target for rational drug design. The two
      classes of anti-EGFR agents in late-stage clinical testing include antibodies
      directed toward the extracellular EGFR domain (cetuximab, panitumumab) and small
      molecule tyrosine kinase inhibitors (gefitinib, erlotinib), which inactivate the
      receptor enzyme activity. However, important issues remain to be addressed. These
      include the development of appropriate predictive markers for response, such as
      improved tests for EGFR activity, correlation of rash with response and potential
      pharmacogenomic approaches; the sequencing and combination of these agents with
      chemotherapy and irradiation; and the possible role of these agents in the
      treatment of patients with earlier stage disease.

PMID- 15846114
TI  - Rapid up-regulation of cyclooxygenase-2 by 5-fluorouracil in human solid tumors.
AB  - Inhibition of cyclooxygenase (COX)-2 has been associated with reduced growth of
      malignant cells. Current therapy of gastrointestinal carcinomas involves the use
      of 5-fluorouracil (5-FU)-based chemotherapy and we have therefore studied the
      effect of this agent on the expression of COX-2. COX-2 expression was measured by
      quantitative RT-PCR in biopsies from a series of 14 esophageal carcinomas, six of
      which had paired samples taken before and after chemotherapy, and in tumor
      derived cells exposed to 5-FU in vitro from a series of 44 tumors, including
      breast, ovarian, esophageal and colonic carcinomas. COX-2 expression was
      increased by exposure to 5-FU or 5-FU combination chemotherapy in all the tumor
      types studied, whether measured in biopsies taken before and after 5-FU-based
      chemotherapy (4-fold increase, p<0.015) or in primary cells exposed to drugs in
      vitro (24-fold increase, p<0.001). A modest increase of COX-2 mRNA was also seen
      after in vitro treatment of cells with cisplatin. In contrast, doxorubicin and
      paclitaxel caused no up-regulation in vitro, while irinotecan caused inhibition
      of COX-2 (2.7-fold decrease, p<0.01). These data provide a molecular rationale
      for clinical trials of combination chemotherapy with COX-2 inhibitors.

PMID- 15846115
TI  - Evaluation of cisplatin and a novel platinum polymer conjugate for drug toxicity
      and drug distribution in mice.
AB  - The toxicity and distribution of cisplatin and two novel platinum (Pt) polymer
      conjugates (Pt-6 and Pt-7) were determined in serum and tissue of BALB/c mice at
      specific time points after i.p. administration of a drug bolus containing
      identical Pt concentrations. Pt concentrations were determined in serum, liver
      and kidney at 5 and 15 min, respectively, after drug administration by
      inductively coupled plasma mass spectrometry. It was found that the Pt polymer Pt
      7 gave rise to a considerably lower Pt concentration in serum and considerably
      higher concentration in liver and kidney than cisplatin. LD25 measurements
      indicated that the Pt-7 polymer is considerably less toxic than cisplatin. In
      vitro experiments and determination of IC50 values in a variety of human tumor
      cell lines, normal lymphocytes and fibroblasts confirmed that Pt-6 and Pt-7
      polymers are 40-500 times more toxic for tumor cells than for normal cells,
      perhaps reflecting preferential uptake. The toxicity of cisplatin was found to be
      only 1.6-40 times more effective in tumor cells. These inter-relationships are
      supported by the observation that the tumor enrichment factor (TEF) for cisplatin
      is only in the region of 6, and much lower than for Pt-6 and Pt-7, where TEFs are
      in the region of 40 and 150, respectively. These results demonstrate that the Pt
      polymer conjugates exhibit greater tumor specificity than cisplatin, killing
      tumor cells more effectively while being considerably less toxic for normal
      cells. It is concluded that the Pt polymer conjugates may be superior for cancer
      therapy and warrant further testing to assess their full clinical potential.

PMID- 15846116
TI  - Induction of apoptosis and inhibition of cyclooxygenase-2 expression by N-methyl
      N'-nitro-N-nitrosoguanidine in human leukemia cells.
AB  - Previous studies have demonstrated that N-methyl-N'-nitro-N-nitrosoguanidine
      (MNNG), a well-known DNA alkylating agent, induces G2/M arrest and apoptotic cell
      death in several human cancer cell lines. In the present study, we investigated
      the effects of MNNG on the growth of a U937 human leukemia cell model. The
      effects of this compound were also tested on cyclooxygenase (COX) activity.
      Treatment of U937 cells with MNNG resulted in the inhibition of viability and the
      induction of apoptosis in a concentration-dependent manner, which was associated
      with a dose-dependent upregulation in pro-apoptotic Bax protein, downregulation
      of anti-apoptotic Bcl-2 and Bcl-xL proteins, and proteolytic activation of
      caspase-3 protease. Furthermore, MNNG decreased the levels of COX-2 mRNA and
      protein expression without significant changes in the levels of COX-1, which was
      correlated with inactivation of the reporter construct of a COX-2 promoter and
      decrease in prostaglandin E2 synthesis. Taken together, these findings provide
      important new insights into the possible molecular mechanisms of the anti-cancer
      activity of MNNG.

PMID- 15846117
TI  - 11,11'-dideoxy-verticillin: a natural compound possessing growth factor receptor
      tyrosine kinase-inhibitory effect with anti-tumor activity.
AB  - 11,11'-dideoxy-verticillin, a compound of the novel epidithiodioxopiprazine
      structural class, is isolated from the traditional Chinese medicinal herb Shiraia
      bambusicola. The present study demonstrated for the first time that 11,11'
      dideoxy-verticillin has potent tyrosine kinase-inhibitory and anti-tumor
      activities. In the cell-free ELISA tyrosine kinase assay, 11,11'-dideoxy
      verticillin significantly inhibited the activities of epidermal growth factor
      receptor (EGFR), vascular endothelial growth factor receptor-1/fms-like tyrosine
      kinase-1 (VEGFR-1/Flt-1) and human epidermal growth factor receptor-2 (HER2/ErbB
      2), with relative specificity on EGFR and VEGFR-1 with IC50s of 0.136+/-0.109 and
      1.645+/-0.885 nM, respectively. Exposure of 11,11'-dideoxy-verticillin for 1 h to
      EGFR-overexpressed MDA-MB-468 human breast carcinoma cells and HER2-overexpressed
      SK-OV-3 human ovarian adenocarcinoma cells resulted in obvious inhibition of EGF
      induced phosphorylation of EGFR and HER2. In addition, 11,11'-dideoxy-verticillin
      also inhibited the EGF-induced phosphorylation of Erk1/2, but had no effect on
      the phosphorylation of AKT in both tumor cell lines. Moreover, 11,11'-dideoxy
      verticillin has potent anti-tumor activity. In vitro cytotoxicity assay showed
      that 11,11'-dideoxy-verticillin potently inhibited the proliferation of four
      human breast tumor cell lines with an average IC50 value of 0.2 microM. In vivo,
      11,11'-dideoxy-verticillin exhibited remarkable efficacy against mice sarcoma 180
      and hepatoma 22 after daily i.p. administration of 0.5 or 0.75 mg/kg with
      inhibition rates ranging from 45.0 to 72.4%. Treated with 11,11'-dideoxy
      verticillin at 0.5-2.0 microM for 36 h, MB-MB-468 cells exhibited significant
      apoptotic morphological changes. At low concentrations (0.0625-0.5 microM) for 24
      h, 11,11'-dideoxy-verticillin induced a dose-dependent accumulation of MDA-MB-468
      cells in the G2/M phase of the cell cycle. These results indicate that 11,11'
      dideoxy-verticillin is a naturally derived growth factor receptor tyrosine kinase
      inhibitor with potent anti-tumor activity.

PMID- 15846118
TI  - Predicting the chemosensitivity of ovarian and uterine cancers with the collagen
      gel droplet culture drug-sensitivity test.
AB  - We investigated the utility of the collagen gel droplet culture drug-sensitivity
      test (CD-DST) for predicting the response of gynecological cancers to
      chemotherapy. Eighty-three cancer patients were enrolled in this study: 26
      ovarian, 29 cervical and 31 endometrial cancers. The CD-DST was performed at
      various concentrations of drugs. We calculated the T/C ratio, where T is the
      total volume of the treated culture and C is the total volume of the control
      culture, and a T/C ratio of 50% or less was defined as sensitive in vitro. The
      efficacy rate (%) was defined as the number of cultures with a T/C ratio of 50%
      or less, divided by the total number of evaluable cultures. True-positive cases
      were defined as clinical responders (complete+partial responses) and true
      negative cases were defined as clinical non-responders. The overall tumor
      evaluation rate was found to be 79.1%. The appropriate drug concentrations were
      selected as 1.0 microg/ml for cisplatin, 20.0 microg/ml for carboplatin, 1.0
      microg/ml for paclitaxel and 0.1 microg/ml for docetaxel by the linear regression
      equations. The in vitro sensitivity for each drug showed a significant
      correlation with clinical response rates (r=0.592, p=0021). We therefore conclude
      that the CD-DST can be used to predict the response to anti-cancer drugs, and may
      also provide important information by contributing to the development of new
      chemotherapy regimens.

PMID- 15846119
TI  - The patellazoles inhibit protein synthesis at nanomolar concentrations in human
      colon tumor cells.
AB  - The patellazoles are a family of compounds consisting of a 24-member macrolide
      ring with a thiazole-epoxide tail. The opening of this epoxide does not greatly
      affect the bioactivity of these compounds, although the cellular toxicity is
      generally decreased. The patellazoles are extremely cytotoxic towards HCT 116
      human colon tumor cells. Treatment with nanomolar amounts of these compounds
      results in immediate inhibition of protein synthesis and cell cycle arrest at the
      G1 and S phase. HCT 116 wild-type cells underwent apoptosis after extended
      patellazole treatment. Although treatment with the patellazoles resulted in an
      increased amount of p53, the p53 null cells were still strongly affected by
      treatment. The inhibition of translation by patellazole treatment is linked to
      the inhibition of the mTOR/p70 pathway. Like the mTOR inhibitor rapamycin, the
      patellazoles inhibit translation through the 4EBP1 and S6 kinase pathways.
      However, the cytotoxicity of rapamycin and the patellazoles differs greatly in
      HCT 116 cells. The cellular target of the patellazoles is still unknown; the
      patellazole-induced inhibition of this pathway occurs either downstream or
      parallel to AKT.

PMID- 15846120
TI  - Growth inhibition and apoptosis induction of human melanoma cells by omega
      hydroxy fatty acids.
AB  - We examined the anti-tumor activity and structure-activity requirements of omega
      hydroxy fatty acids (omega-HFAs) on the human melanoma cell line G361. The omega
      hydroxystearic acid (omega-HSA) had strong growth-inhibiting and cytotoxic
      activity. Although omega-hydroxypalmitic acid (omega-HPA) also had growth
      inhibiting and cytotoxic activity, these effects were relatively low. The effects
      of both these acids were dose and time dependent. Further, DNA laddering, which
      is an index of apoptosis, was also observed in G361 cells on treatment with these
      compounds. On the other hand, the omega-HFAs tested in this study, omega
      hydroxymyristic acid and omega-hydroxyeicosanoic acid, had no growth-inhibiting
      or cytotoxic activity. Treatment for 12 h with 100 microM of omega-HPA and omega
      HSA resulted in the expression of caspase-3 activity, and then increased upon 24
      h, suggesting that the cell death induced by omega-HPA and omega-HSA was
      apoptosis. Fatty acids and dicarboxylic acids, which are analogs of omega-HFAs,
      had no cytotoxicity. However, fatty alcohols and diols, which have a 16- to 18
      carbon chain length had weak cytotoxicity. From these results, the most effective
      carbon chain length is 18. Furthermore, the hydroxyl group at one end of the
      carbon chain and the carboxyl group at the other end seem to be required for the
      cytotoxic effect. At least one end of the carbon chain must have a hydroxyl
      group. The carbon chain length of omega-HFAs appears to be closely related to the
      cytotoxicity. This study revealed the potent cytotoxic actions of omega-HFAs on
      the human melanoma cell line G361.

PMID- 15846121
TI  - Synergistic anti-tumor effect of recombinant human endostatin adenovirus combined
      with gemcitabine.
AB  - Endostatin is an important endogenous inhibitor of neovascularization, which has
      been widely used in anti-angiogenesis therapy for cancer. To fully explore the
      potential of endostatin, we evaluated the anti-tumor efficacy of the combination
      of recombinant human endostatin adenovirus and low-dose gemcitabine in nude mice.
      We injected recombinant human endostatin adenovirus intratumorally plus a low
      dose of gemcitabine i.p. routinely. The combination treatment produced no side
      effects, and resulted in marked suppression in tumor formation and growth of
      established human lung carcinoma xenografts in nude mice, with decreased
      microvessel density and increased apoptosis percentage. Our data support the idea
      of synergistic anti-tumor properties of endostatin plus low-dose chemotherapy
      against human lung cancer in vivo.

PMID- 15846122
TI  - Dose-dependent effects of 4-hydroxytamoxifen, the active metabolite of tamoxifen,
      on estrogen receptor-alpha expression in the rat uterus.
AB  - Tamoxifen, a selective estrogen receptor modulator, has agonist or antagonist
      activity, depending on the target tissue. The estrogen-like agonist effects of
      tamoxifen in the uterus are mediated primarily by 4-hydroxytamoxifen (4OH), the
      major active metabolite. Tamoxifen, 4OH and estradiol-17beta (E2) all bind to
      estrogen receptors (ERalpha and ERbeta), but with different affinities,
      suggesting that these ligands are capable of producing differential in vivo
      effects on the uterus. However, differences in short-term effects of tamoxifen,
      4OH and E2 on the uterus have not been compared in the rat in vivo. Thus, we
      treated adult, ovariectomized rats (225-250 g) with vehicle (sesame oil),
      tamoxifen (1 mg/kg body weight), 4OH (0.01, 0.1 or 1.0 mg/kg body weight), E2 (40
      microg/kg body weight), estradiol valerate (a long-lasting estrogen; 40 microg/kg
      body weight) or ICI 182,780 (a pure anti-estrogen; 1 mg/kg body weight). Animals
      were sacrificed at 0, 3, 6, 12 or 24 h post-injection, and protein and mRNA
      levels for ERalpha and two estrogen-regulated early response genes, c-fos and jun
      B, were examined. Administration of E2 and 4OH (1 mg/kg body weight dose)
      resulted in down-regulation of uterine ERalpha protein in the uterine luminal and
      glandular epithelium by 6 h post-treatment. In contrast, no change in ERalpha
      level was observed after treatment with tamoxifen. Rapid (by 3 h) and transient
      increases in c-fos and jun-B mRNA levels were observed after E2 treatment;
      however, c-fos and jun-B induction by 4OH was highly dose dependent, and higher
      4OH doses induced rapid but persistent proto-oncogene expression in vivo. Our
      results demonstrate that tamoxifen and its major metabolite have differential
      effects on uterine gene expression, and 4OH is highly estrogenic in the rat
      uterus.

PMID- 15846123
TI  - Combined oral delivery of ebselen and allopurinol reduces multiple cisplatin
      toxicities in rat breast and ovarian cancer models while enhancing anti-tumor
      activity.
AB  - The chemoprotective effects of combined ebselen and allopurinol in breast (MTLn3)
      and ovarian (NuTu-19) cancer models using a repeated cisplatin dosing schedule (6
      mg/kg i.p.x3 weeks) were studied. Otoprotection was evaluated using auditory
      evoked brainstem response (ABR) to determine threshold and latency shifts, and
      outer hair cell counts. Nephroprotection was analyzed by serological markers
      [blood urea nitrogen (BUN) and creatinine] and histological evaluation.
      Myelotoxicity was quantified using cytological counts for platelets and changes
      in hematocrit. Hepatotoxicity was determined by changes in the serological
      markers amino alanine transferase (ALT) and aspartate amino transferase.
      Significant chemoprotective effects were observed for multiple organ systems
      including oto- (ABR threshold shifts for click and 24-kHz stimuli, p<0.05, 8 and
      16 kHz, p<0.01, MTLn3 group; hair cell counts, p<0.05 both groups), nephro- (BUN
      and creatinine, p<0.01), myelo- (platelet p<0.05, hematocrit p<0.05) and
      hepatotoxicity (ALT p<0.05) in rats receiving oral ebselen and allopurinol.
      Importantly, the anti-tumor activity of cisplatin was not compromised. On the
      contrary, improved mortality, morbidity and outcome were observed in the ovarian
      cancer model. This combined oral formulation of ebselen and allopurinol is an
      attractive candidate for clinical evaluation.

PMID- 15846124
TI  - Application of thalidomide/interleukin-2 in immunochemotherapy-refractory
      metastatic renal cell carcinoma.
AB  - Thalidomide has been reported to yield anti-tumor activity in advanced renal cell
      carcinoma (RCC). We evaluated safety and efficacy of a combination therapy
      comprising interleukin (IL)-2 and thalidomide in patients with metastatic RCC
      refractory to both immuno- and chemotherapy. Twelve patients with progressive
      metastatic RCC who had failed prior treatment with immunochemotherapy and desired
      further active therapy were enrolled in this study. Oral thalidomide was started
      at 200 mg/day and escalated after 2 days to 400 mg/day at week 0. IL-2 at 7 MIU/m
      was given by s.c. injection, starting at week 1, days 1-5, weeks 1-4, with rest
      from IL-2 at weeks 5 and 6. Response was assessed every two therapy cycles. Ten
      patients were evaluable for response. There was no objective response; four
      patients showed stable disease for 14+, 11+, 10+ and 9 months, respectively.
      Toxicities were predominantly grade I-II, and included somnolence and
      constipation, as well as flu-like symptoms associated with IL-2. However, one
      patient developed serious constipation which led to a paralytic ileus and
      discontinuation of treatment. Another patient left the study after 7 weeks due to
      increasing disorientation/confusion. Eight patients required IL-2 dose reduction.
      Time on therapy ranged from 3 to 44 weeks (median 20 weeks). Median overall
      survival was 12+ months. At present, all patients have discontinued treatment. We
      conclude that outpatient administration of thalidomide/IL-2 is feasible in
      patients with heavily pretreated and progressive RCC who desire further active
      treatment. However, toxicity and costs are considerable, and clinical benefit is
      uncertain. Therefore, thalidomide/IL-2 might not represent a promising
      therapeutic approach for this subgroup of patients.

PMID- 15846125
TI  - Clinical activity of venlafaxine and topiramate against oxaliplatin-induced
      disabling permanent neuropathy.
AB  - Venlafaxine (Effexor; Wyeth Lederle), a serotoninergic-like anti-depressant, and
      Topiramate (Epitomax; Jansen Cilag), a new anti-epileptic drug, share some
      evidence of clinical activity in the treatment of neuropathic pain. Several anti
      cancer agents have neurosensory toxicity as limiting toxicity of their repeated
      administration. One of the most recent and the most widely used is oxaliplatin.
      No medication is presently known to be active against oxaliplatin permanent
      neurosensory toxicity. We observed that venlafaxine hydrochloride or low-dose
      topiramate could be active against the permanent neuropathy-related symptoms of
      oxaliplatin. Both agents allowed pain relief and a significant autonomy
      improvement. These preliminary results invite us to evaluate further venlafaxine
      hydrochloride and topiramate for the treatment of permanent anti-cancer
      chemotherapy-induced neuropathies.

PMID- 15846140
TI  - Lovastatin-induced apoptosis in human melanoma cell lines.
AB  - The cholesterol-lowering medications, statins, inhibit cellular proliferation and
      induce apoptosis in an array of cancer cell lines, including melanoma. We
      investigated the apoptotic mechanism of lovastatin on human melanoma cell lines
      in vitro. The cytotoxicity of statins on multiple cell lines was examined by Cell
      Titer 96 Aqueous One solution cell proliferation assay (MTS assay). Apoptosis was
      assayed by ethidium bromide and acridine orange morphologic assays, an Annexin V
      apoptosis detection kit and active caspase 3 assays. Farnesyl pyrophosphate and
      geranylgeranyl pyrophosphate add-back experiments were performed to better define
      the molecular mechanisms mediating lovastatin cytotoxicity. Lovastatin caused
      cytotoxicity in human and murine melanoma cells, but did not induce toxicity in
      an epidermoid carcinoma cell line A431. For human melanoma cells, lovastatin
      precipitated cell rounding, increased the percentage of apoptotic cells detected
      by ethidium bromide and acridine orange staining and by the Annexin V apoptosis
      detection kit, and resulted in a 50-fold increase in active caspase 3,
      corroborating that lovastatin induced apoptosis. Adding back geranylgeranyl
      pyrophosphate, but not farnesyl pyrophosphate, reversed the effects of lovastatin
      in A375 cells. Of the five statins tested, pravastatin was least effective in
      killing melanoma cells. Lovastatin induced caspase-dependent apoptosis in
      multiple melanoma cell lines via a geranylation-specific mechanism. This study
      supports a possible role of lovastatin as a therapeutic, adjuvant or
      chemopreventive agent for melanoma.

PMID- 15846141
TI  - The prevalence of interferon-alpha transcription defects in malignant melanoma.
AB  - The type I interferons, interferon-alpha (IFN-alpha) and interferon-beta (IFN
      beta), are situated on the short arm of chromosome 9, specifically 9p21-22. This
      locus lies very close to an area that is deleted or rearranged in nearly half of
      all melanomas tested. The identification of 9p rearrangements in both melanoma
      precursor lesions (dysplastic naevi) and primary lesions has implicated the 9p
      locus in the early stages of melanoma development. Recent evidence has
      demonstrated that metastatic melanoma cell lines have a specific loss of IFN
      alpha gene expression, a defect that appears to occur at the level of
      transcription. In this study, we examined the expression of IFN-alpha in cell
      lines isolated from the various stages of melanoma progression, with a view to
      determine the prevalence of the IFN-alpha transcription defects exhibited by
      malignant melanoma, and to assess whether the loss of IFN-alpha expression was
      particular to a certain stage of melanoma progression. We showed that all the
      melanoma cell lines tested (n=20) demonstrated an inability to express IFN-alpha,
      a defect that was reflected in the apparent inactivity of the IFN-alpha promoter.
      These defects were found to occur in cells isolated from early melanomas, lending
      support to the hypothesis that IFN-alpha has a role in the aetiology of malignant
      melanoma.

PMID- 15846142
TI  - Cytokine expression and dendritic cell density in melanoma sentinel nodes.
AB  - The sentinel lymph node (SLN) is the first draining node from the area in which a
      tumour is located. The presence or absence of SLN micrometastasis is an important
      prognostic factor for melanoma. As the first dissemination route for melanoma is
      lymphatic and we know that the immune system plays an important role in melanoma
      response, we hypothesize that melanoma and its corresponding SLN should
      constitute an immunological unit. Small portions of 54 SLNs from 37 patients
      undergoing selective lymphadenectomy were subjected to quantitative reverse
      transcriptase-polymerase chain reaction (qRT-PCR) to quantify messenger RNA
      (mRNA) transcripts of the following genes: tyrosinase, telomerase, cyclooxygenase
      1 (COX-1), COX-2, granulocyte-macrophage colony-stimulating factor (GM-CSF),
      interleukin-2 (IL-2), interferon-gamma (IFN-gamma), IL-4, IL-10 and IL-12. In
      addition, 11 non-sentinel lymph nodes (NSLNs) were excised from 11 of the 37
      patients and the same study was performed. Immunohistochemistry with different
      antibodies against dendritic cells (DCs) was performed in 10 pairs of SLNs and
      NSLNs. Significantly higher mRNA expression of COX-2, GM-CSF, IFN-gamma and IL-10
      was found in SLNs compared with NSLNs in the overall group. DCs, as labelled by S
      100 and CD1a, were significantly decreased in NSLNs compared with SLNs. These
      data suggest that the initial increase in GM-CSF observed in SLNs could lead to
      the attraction of a high number of DCs to SLNs. However, the presence of certain
      immunosuppressive molecules, such as IL-10 and COX-2, could block their
      maturation and their ability to become efficient antigen presenters.

PMID- 15846143
TI  - Immunohistochemical detection of incipient melanoma micrometastases. Relationship
      with sentinel lymph node involvement.
AB  - It is acknowledged that tumour thickness, ulceration and lymph node invasion are
      the most important prognostic factors for cutaneous melanomas. Other
      histopathological features may also be informative. The aim of this study was to
      ascertain whether immunohistochemical methods can improve the detection of
      satellite micrometastases in primary melanoma patients. In addition, the
      predictive value of cutaneous satellite micrometastases for sentinel lymph node
      involvement was evaluated. A total of 265 primary cutaneous melanomas and 68 of
      the respective sentinel nodes were studied using a panel of seven antibodies
      directed against melanocyte-related antigens. In 12.4% of the 265 cases, small
      satellite micrometastases were detected by immunohistochemistry. Sentinel lymph
      node metastases were found in 14% of the 68 cases. Invasion of the sentinel lymph
      node correlated with the presence of cutaneous satellite micrometastases. It is
      concluded that the presence of cutaneous satellite micrometastases may be an
      indication for the performance of sentinel lymph node biopsy, and this finding
      calls for a closer follow-up of these patients.

PMID- 15846144
TI  - Cross-reactivity of mimotopes with a monoclonal antibody against the high
      molecular weight melanoma-associated antigen (HMW-MAA) does not predict cross
      reactive immunogenicity.
AB  - The high molecular weight melanoma-associated antigen (HMW-MAA) is highly
      expressed in advanced primary and metastatic melanoma. An epitope of the core
      protein of HMW-MAA is recognized by the murine monoclonal antibody (mAb) 225.28S.
      In this study, we aimed to characterize peptides that antigenically mimicked this
      epitope and to determine their efficacy as components of an HMW-MAA-based anti
      melanoma vaccine. Therefore, we screened a constrained 10 mer phage display
      peptide library against mAb 225.28S. Selected phage-displayed peptides were then
      tested for their specificity for the antibody's antigen-binding site. DNA
      sequences coding for specific peptide ligands were determined. Binding of mAb
      225.28S to HMW-MAA was inhibited in a dose-dependent manner by phage-displayed
      peptides from 51 to 83% and by synthetic peptides from 38 to 87%. Subsequently,
      the immunogenicity of the five mimotopes with the highest inhibition capacity was
      examined in rabbits. Immunizations with synthetic mimotopes conjugated to tetanus
      toxoid resulted in peptide-specific antibodies, but none of the highly antigenic
      mimotopes induced HMW-MAA cross-reactive antibodies. This report describes an
      example of disparity between antigenicity and cross-reactive immunogenicity,
      complicating the selection of potential vaccine candidates.

PMID- 15846145
TI  - Increased incidence of brain metastases in cutaneous head and neck melanoma.
AB  - The incidence of cutaneous melanoma is increasing, and 10-20% of these melanomas
      are located in the head and neck region. The incidence of brain metastases, risk
      factors and outcome were analysed for melanomas originating in the head and neck
      region. During the period 1965-2000, 324 patients [152 females (47%), 172 males
      (53%)] were treated for cutaneous melanoma of the head and neck. The patients
      were staged according to the 2002 American Joint Committee on Cancer (AJCC)
      melanoma staging system. A matched control analysis was performed in order to
      identify the risk factors for the occurrence of brain metastases. The analysis
      was performed using cross-tabulations, chi-squared test and the logistic
      regression method. Twenty six (8%) head and neck patients, compared with 5.2% of
      extremity/truncal patients, developed brain metastases (confidence interval,
      0.058-0.108; P<0.05). The 26 head and neck patients (four Stage I, 10 Stage II
      and 12 Stage III) had a median age of 46 years (range, 16-79 years) and developed
      brain metastases after a median follow-up of 24 months (range, 4-75 months). The
      median Breslow thickness was 3.3 mm (range, 0.7-12 mm). The patients were treated
      with steroids, surgery, radiation, chemotherapy, or a combination of these. The
      median survival after the development of brain metastases was 2.4 months (range,
      0.2-64.3 months), with a 1-year overall survival of 15%. Risk factors identified
      for the development of brain metastases from head and neck melanoma were a
      younger age, male gender, Breslow thickness greater than 4 mm and increased
      mitotic rate. The incidence of brain metastases is significantly higher in
      patients with cutaneous melanoma of the head and neck (8%) compared with those
      with extremity/truncal melanoma (5.2%). The prognosis is still extremely poor
      with current therapies.

PMID- 15846146
TI  - Effect of primary site on prognosis in patients with cutaneous malignant
      melanoma. A study using a new model to analyse anatomical locations.
AB  - The prognostic impact of different anatomical sites in patients with cutaneous
      malignant melanoma (CMM) has been widely debated and requires further
      elucidation. Therefore, we developed EssDoll, a new computerized method to
      address the question of site in relation to prognosis. A population-based cohort
      of 1891 patients, diagnosed between 1976 and 1987 with invasive CMM without
      evidence of metastasis, was identified. The body surface was divided into 24
      areas. Hazard ratios (HRs) for CMM death were calculated and areas were compared
      in both the whole model and in pairs. Cox's proportional hazard regression model
      was used and adjustments were made for established prognostic factors.
      Furthermore, the overall effect of site was calculated using the likelihood ratio
      test. Overall, the tumour site was of prognostic importance (P=0.0036). There was
      a significantly increased risk of CMM-specific death in patients with a primary
      tumour site in the middle and lower back (HR=1.8, P=0.04) and in the supramammary
      and mammary area (HR=1.8, P=0.05). When all areas were analysed in pairs, the
      dorsal shoulder, superior back and clavicular area also showed a worse prognosis.
      CMM diagnosed in other anatomical regions, including the calves, Achilles, upper
      arms, forehead, temples, cheeks and face, seemed to be related to a better
      prognosis. It can be concluded that the tumour site is of prognostic importance,
      and that the middle and lower back and supramammary and mammary areas are
      independent factors related to a poor prognosis.

PMID- 15846147
TI  - A case of perineal malignant melanoma successfully treated with
      electrochemotherapy.

PMID- 15846148
TI  - Spleen rupture due to metastasis of thin melanoma (Breslow thickness of 0.75 mm).

PMID- 15846151
TI  - Antimicrobial susceptibility breakpoints: PK-PD and susceptibility breakpoints.
AB  - Since the early 1960s, considerable advancements have been made to standardize
      and provide quality assurance for clinical susceptibility testing procedures of
      antimicrobial agents. Controversy, however, remains as to the interpretation of
      clinical laboratory susceptibility test results. While some feel susceptibility
      breakpoints should only detect resistance mechanisms, others believe they should
      predict a high probability of clinical response. This has resulted in confusion
      among clinicians, as it has been apparent for some time that there can be
      discordance between interpretive test results and clinical response to therapy
      (generally cures of infections caused by resistant pathogens). Nearly
      simultaneous with the beginning of the standardization process for clinical
      susceptibility testing procedures, the first penicillin-resistant Streptococcus
      pneumoniae isolates were detected. During the ensuing decades, penicillin
      resistant pneumococci became a greater clinical concern, resulting in macrolides
      emerging as safe therapeutic alternatives to beta-lactam agents for the treatment
      of community-acquired respiratory tract infections. During the last 10 years, the
      incidence of pneumococcal isolates with elevated macrolide minimum inhibitory
      concentration (MIC) values has also increased, yet the debate over the clinical
      meaning of these statistics persists. The youthful science of pharmacokinetics
      pharmacodynamics provides a useful platform to determine which pneumococcal
      strains with elevated MIC values can be treated with contemporary dosing regimens
      and also facilitates the proper selection of antimicrobial breakpoints for all
      antimicrobial classes, including the newer macrolides.

PMID- 15846150
TI  - Antimicrobial resistance with bacterial causes of community-acquired respiratory
      tract infections in the United States.

PMID- 15846152
TI  - Antibacterial drivers of resistance.
AB  - Increased levels of antibacterial resistance among community-acquired pathogens
      have been influenced by various factors. Among the antibacterial-related drivers
      of resistance, the inappropriate and excessive use of antibacterials has been
      identified. A large number of antibacterial prescriptions can be attributed to
      syndromes of viral etiology; given that antibacterials provide no clinical
      benefit, this represents an important target for decreasing unnecessary
      antibacterial use. Notably, therapeutic exposure of bacteria to antibacterials
      exerts a continuous selection pressure on pathogens as well as on normal flora.
      This selection pressure may favor and/or enable resistance development through
      various mechanisms. The development of resistance may be reduced by avoiding
      subtherapeutic antibacterial exposure and prolonged treatment durations. Potency,
      or the product of in vitro antibacterial activity and the ability of an
      antibacterial to achieve adequate concentrations at the site of infection, is
      also a critical consideration. In general, the more potent an antibacterial, the
      less likely it is to propagate resistant isolates. Antibacterial resistance is
      unavoidable. However, consideration of the drivers of resistance and concerted
      efforts to avoid these effects will help to better control the development of
      resistance.

PMID- 15846153
TI  - Clinical significance of pneumococcal resistance and factors influencing
      outcomes.
AB  - Despite increasing penicillin and macrolide resistance worldwide, the clinical
      relevance of this phenomenon is still unknown. Debate continues as to whether
      increasing resistance among pneumococci to beta-lactam agents, macrolides, and
      fluoroquinolones has been accompanied by an increase in the rate of treatment
      failure. In vitro findings do not appear to be predictive of in vivo outcomes.
      Studies have failed to demonstrate significantly higher mortality for patients
      infected with penicillin-resistant rather than penicillin susceptible
      pneumococcal strains. Treatment failures are associated solely with the highest
      levels of resistance. Antimicrobial resistance appears to affect other markers of
      morbidity, but only statistically nonsignificant trends toward increased
      mortality have been demonstrated. Whether macrolide resistance among invasive
      pneumococcal isolates is clinically relevant or a matter of limited influence
      remains to be determined.

PMID- 15846154
TI  - Solutions to the problem of bacterial resistance.
AB  - The recent increase in bacterial resistance has been, and continues to be,
      unmatched by drug discovery and development. The judicious use of antibacterials
      must be observed so as to contain bacterial resistance and maintain the utility
      of agents currently on the market. Appropriate antibacterial use involves
      antibacterial avoidance when not indicated. When indicated, appropriate
      antibacterial use dictates that the optimal drug, dose and duration be utilized.
      Professional society guidelines facilitate drug selection as well as outline
      diagnostic criteria and important considerations for patient stratification.
      Pharmacodynamics is also key for drug selection and often guides determination of
      not only the optimal drug but also the optimal dose and duration. Importantly,
      bacterial eradication is essential, as it will reduce clinical failure,
      recurrence, or relapse and prevent the selection of resistance. Additional
      strategies to influence antibacterial prescribing and use such as formal
      continuing medical education, printed educational materials, better diagnostic
      tests, and vaccination contribute to the efforts to minimize bacterial resistance
      and are also addressed.

PMID- 15846155
TI  - Rapid full volume data acquisition by real-time 3-dimensional echocardiography
      for assessment of left ventricular indexes in children: a validation study
      compared with magnetic resonance imaging.
AB  - OBJECTIVE: We sought to assess the feasibility, accuracy, and reproducibility of
      a rapid full volume acquisition strategy using real-time (RT) 3-dimensional (3D)
      echocardiography (3DE) for measurement of left ventricular (LV) volumes, mass,
      stroke volume (SV), and ejection fraction (EF) in children. METHODS: A total of
      19 healthy children (mean 10.6 +/- 2.8 years, 11 male and 9 female) were
      prospectively enrolled in this study. RT 3DE was performed using an ultrasound
      system to acquire full volume 3D dataset from the apical window with
      electrocardiographic triggering in 8 s/dataset. The images were processed offline
      using software. The LV endocardial and epicardial borders were traced manually to
      derive LV end-systolic volume, end-diastolic volume, mass, SV, and EF. Magnetic
      resonance imaging (MRI) studies were performed on a 1.5-T scanner using a breath
      hold 2-dimensional cine-FIESTA (fast imaging employing steady-state acquisition)
      sequence. RESULTS: All RT 3DE and MRI data were acquired successfully for
      analysis. Measurements of LV end-systolic volume, end-diastolic volume, mass, SV,
      and EF by RT 3DE correlated well by Pearson regression ( r = 0.86-0.97, P < .001)
      and agreed well by Bland-Altman analysis with MRI. The interobserver and
      intraobserver variability of RT 3DE measurements were less than 5%. CONCLUSIONS:
      This prospective study demonstrated that RT 3DE measurements of LV end-systolic
      volume, end-diastolic volume, mass, SV, and EF in children using rapid full
      volume acquisition strategy are feasible, accurate, and reproducible and are
      comparable with MRI measurements.

PMID- 15846156
TI  - Automated mitral annular tracking: a novel method for evaluating mitral annular
      motion using two-dimensional echocardiography.
AB  - We developed an automated mitral annular tracking method based on a digital
      processing of high frame rate cineloop images of 2-dimensional echocardiography.
      In this study, its feasibility and accuracy was validated in 11 healthy
      volunteers and 16 patients with left ventricular (LV) dysfunction. The mitral
      annular excursion measured by automated mitral annular tracking agreed well with
      that measured by 3-dimensional echocardiography and correlated with LV ejection
      fraction. The longitudinal mitral annular excursion was reduced whereas the
      radial one was preserved for patients with LV dysfunction compared with control
      subjects. The novel automated mitral annular tracking method is clinically
      feasible and has potential capability to quantify the comprehensive mitral
      annular motion for evaluating LV function in a clinical setting.

PMID- 15846157
TI  - Use of a hand-carried ultrasound device by critical care physicians for the
      diagnosis of pericardial effusions, decreased cardiac function, and left
      ventricular enlargement in pediatric patients.
AB  - Prompt diagnosis of children with suggested cardiac disease in the acute care
      setting is critical for initiation of life-saving therapy. We hypothesized that
      pediatric critical care physicians could perform limited portable
      echocardiography in children. Portable hand-carried cardiac ultrasound units with
      2.5-MHz phased-array transducers were used (Optigo, Philips Medical Systems,
      Andover, Mass). Noncardiologists were trained through a 1-hour introductory
      course and 2 hours of practical training. Portable echocardiography performed by
      noncardiologists was compared with a standard echocardiogram for diagnostic
      accuracy. In all, 23 patients (age 3 months-20 years) were screened during 18
      months. The presence or absence of a pericardial effusion was correctly diagnosed
      in 21 of 23 patients (91%). Left ventricular size was correctly determined in 22
      of 23 patients (96%). Left ventricular systolic function was correctly diagnosed
      in 22 of 23 patients (96%). These results show that, with appropriate
      instruction, pediatric critical care physicians are effective using limited
      portable echocardiography.

PMID- 15846158
TI  - Differences in the immediate effects of smoking on left ventricular diastolic
      function between healthy volunteers and patients with type 2 diabetes mellitus.
AB  - BACKGROUND: In contrast to in-depth studies on the chronic hazardous effects of
      smoking, the immediate effects of smoking on left ventricular function have not
      been evaluated in detail. OBJECTIVES: We aimed to assess the hypothesis that
      smoking a cigarette might have more deleterious immediate impacts on left
      ventricular function in patients with diabetes mellitus than in healthy
      volunteers. METHODS: In all, 20 patients with type 2 diabetes mellitus and 25
      healthy volunteers were consecutively enrolled. Mitral inflow parameters (peak
      early and late diastolic velocities, and deceleration time of early diastolic
      mitral inflow) and mitral annulus velocity parameters (systolic, late, and early
      diastolic velocity [E']) were obtained together with heart rate and blood
      pressure before and 5, 15, 30, 45, 60, and 75 minutes after smoking a cigarette.
      RESULTS: Transient elevations in heart rate and blood pressure were observed
      after smoking in both groups. In terms of mitral inflow parameters, transient
      trends toward abnormal relaxation were noted in both groups. For mitral annulus
      velocity parameters, in contrast to a temporary decrease in E' in healthy
      volunteers, reduction in E' persisted throughout the study for patients with
      diabetes. No significant change in peak early diastolic velocity/E' ratio was
      observed in healthy volunteers; however, a significant increase in peak early
      diastolic velocity/E' ratio lasted throughout the study period for patients with
      diabetes. Systolic velocity had no significant change during the study in either
      group. CONCLUSIONS: Even one cigarette can induce more protracted and more severe
      left ventricular diastolic dysfunction in patients with type 2 diabetes mellitus
      than in healthy volunteers. Our results have clinically relevant implications in
      the current era of increasing recognition of the diabetes epidemic and of the
      associated cardiovascular risks.

PMID- 15846159
TI  - Left ventricular inflow propagation velocity at pulsed wave Doppler analysis: an
      index of relaxation.
AB  - To test whether left ventricular inflow propagation velocity at the pulsed wave
      Doppler analysis (IPVpw) is a useful noninvasive index of relaxation, 21 patients
      under coronary angiography for chest pain were included for simultaneous catheter
      based and Doppler studies. IPVpw was derived through the application of range
      ambiguity, and the time constant of isovolumic left ventricular pressure decline
      (tau) was acquired by a previously described method. At baseline status, IPVpw
      correlated significantly with the peak negative dP/dt and tau ( r = -0.609, P =
      .003), but not with the peak velocity of transmitral early flow (E) wave.
      Sublingual application of nitroglycerin increased heart rate, decreased the
      transmitral E velocity and transmitral E-to-A velocity ratio, and prolonged the
      deceleration time of the transmitral E wave. However, there was no significant
      impact on IPVpw, peak negative dP/dt, or tau. IPVpw correlated with tau ( r = 
      0.533, P < .001) at the combined analysis of the data before and after
      nitroglycerin application. In conclusion, IPVpw is a preload-independent,
      noninvasive index of left ventricular relaxation.

PMID- 15846160
TI  - Strain rate analysis allows detection of differences in diastolic function
      between viable and nonviable myocardial segments.
AB  - Analysis of diastolic function for assessment of myocardial viability has not
      been evaluated. Strain rate (SR) analysis allows quantitative segmental analysis
      of myocardial function and has been used during dobutamine stimulation for
      assessment of systolic functional reserve. In 37 patients with ischemic left
      ventricular dysfunction diastolic function was evaluated at rest and during low
      dose dobutamine stimulation (10 mug/kg/min) using SR imaging and related to F18
      fluorodeoxyglucose positron emission tomography. Analysis of peak early (E waves)
      and late (A waves) diastolic myocardial SR was performed using apical views. In
      all, 317 segments had normal function at rest by 2-dimensional echocardiography.
      A total of 192 segments with dyssynergy at rest were classified by positron
      emission tomography as viable in 94 cases and nonviable in 98 cases. Dys-synergic
      segments had lower E and A waves SR compared with normal contracting segments.
      There were no significant differences in peak E and A waves SR at rest between
      dys-synergic viable and nonviable segments. With dobutamine stimulation peak E
      waves SR increased significantly for viable segments (0.89 +/- 0.51-1.06 +/- 0.51
      L/s, P < .01) whereas it was unchanged for nonviable segments (0.77 +/- 0.49-0.78
      +/- 0.48 L/s, P = .835). Peak A waves SR increased for viable (0.71 +/- 0.55-1.00
      +/- 0.56 L/s, P < .01) and nonviable (0.57 +/- 0.47-0.71 +/- 0.58 L/s, P = .023)
      segments. However, during dobutamine stimulation peak A waves SR was larger ( P <
      .001) for viable than for nonviable segments. In conclusion, normal contracting
      segments at rest have higher E and A waves SR compared with dys-synergic
      segments. Dys-synergic viable myocardial segments demonstrate an increase in E
      and A waves SR with dobutamine stimulation whereas nonviable segments are less
      responsive to dobutamine.

PMID- 15846161
TI  - The mitral L wave: a marker of pseudonormal filling and predictor of heart
      failure in patients with left ventricular hypertrophy.
AB  - OBJECTIVES: We sought to examine the relationship of the mitral L wave with
      echocardiographic indexes of diastolic function and heart failure (HF) events in
      patients with left ventricular (LV) hypertrophy (LVH). BACKGROUND: The L wave,
      representing middiastolic transmitral flow, is of unknown clinical and prognostic
      significance in patients with LVH. Methods Consecutive echocardiograms performed
      during a 6-month period were screened for patients with LVH, normal LV ejection
      fraction, in sinus rhythm, and no significant valvular disease. Clinical and
      echocardiographic characteristics were analyzed, and patients were followed up
      for incident HF. RESULTS: Of 177 patients, the L wave was present in 35 (20%)
      (group I) and absent in 142 (group II). Patients in group I had higher early (E)
      to late (A) transmitral flow velocity (E/A) ratio (1.2 vs 0.8), shorter mitral E
      wave deceleration time (201 vs 225 milliseconds), lower pulmonary venous
      systolic/diastolic velocity ratio (1.1 vs 1.6), shorter LV isovolumic relaxation
      time (83 vs 94 milliseconds), larger left atrial volume (36 vs 23 mL/m 2 ), and
      higher E to early mitral annular velocity (E/E') ratio (septal E/E', 12.2 vs 9.1;
      lateral annular E/E', 10.9 vs 7.8) compared with group II (all P < .05). The
      difference between pulmonary venous atrial reversal and mitral A wave durations
      was > or = 30 milliseconds in more patients of group I (70% vs 6%, P < .001).
      During a mean follow-up of 12.0 months, 11 patients were hospitalized for HF. The
      L wave was associated with a hazard ratio of 4.7 ( P = .011) for incident HF, and
      remained a significant predictor (hazard ratio 4.2, P = .026) after adjustment
      for cardiovascular risk factors. CONCLUSIONS: In patients with LVH, the mitral L
      wave appears to be a marker of pseudonormal LV filling and predictor of future HF
      events.

PMID- 15846162
TI  - Index of myocardial performance is afterload dependent in the normal and abnormal
      left ventricle.
AB  - BACKGROUND: The index of myocardial performance (IMP) has been used as a
      prognostic systolic-diastolic index for patients with dilated cardiomyopathy and
      postmyocardial infarction. To date, systematic evaluation of afterload alteration
      (arterial pressure) on IMP has not been performed with normal or reduced left
      ventricular (LV) function. METHODS: We studied 15 mongrel dogs at baseline, after
      the induction of acute ischemic LV dysfunction, and with chronic LV dysfunction.
      Each dog was atrially paced, and the arterial pressure was reduced with
      nitroprusside (NTP) (>10 mm Hg) and increased with methoxamine (Methox) (>30 mm
      Hg) in random order. Hemodynamics and transmitral and transaortic pulsed Doppler
      were obtained. RESULTS: With normal LV function, there were no changes in IMP
      with NTP. Methox reduced IMP (0.51 +/- 0.12-0.45 +/- 0.12, P < .05) as a result
      of a shortened isovolumic contraction time (ICT). With acute LV dysfunction, IMP
      declined with NTP (0.74 +/- 0.19-0.65 +/- 0.17, P < .01) because of a shortened
      ICT and isovolumic relaxation time. Methox prolonged IMP (0.73 +/- 0.16-0.83 +/-
      0.21, P < .05). With chronic LV dysfunction, NTP resulted in a reduced IMP (0.75
      +/- 0.27-0.57 +/- 0.27, P < .01) as a result of a reduced ICT and isovolumic
      relaxation time and a prolonged LV ejection time associated with an increased LV
      ejection fraction. Methox increased IMP (0.72 +/- 0.26-1.31 +/- 0.43, P < .001)
      because of an increased ICT and isovolumic relaxation time and a reduced LV
      ejection time associated with a reduced LV ejection fraction. Forward stepwise
      regression indicated that both LV systolic pressure ( P = .0006) and LV ejection
      fraction ( P = .0222) were independent predictors of IMP. CONCLUSION: IMP is
      afterload dependent in the normal LV. IMP is afterload dependent with acute and
      chronic LV dysfunction by influencing the isovolumic indices and LV ejection time
      in opposite directions. Further systematic evaluation of IMP is needed if this
      index is to be useful as a prognostic indicator.

PMID- 15846163
TI  - Usefulness of low-dose dobutamine stress echocardiography for the evaluation of
      spontaneous recovery of stunned myocardium in patients with acute right
      ventricular infarction.
AB  - Right ventricular (RV) infarction (RVI) is usually associated with severe RV
      global dysfunction representing predominantly stunned myocardium that may respond
      favorably to reperfusion. We assessed the efficacy of low-dose dobutamine stress
      echocardiography (DSE), performed early in the course of a reperfused RVI, to
      predict the recovery of RV systolic and diastolic function in 3 months,
      documenting the recovery of stunned myocardium. In all, 27 patients with acute,
      successfully thrombolyzed RVI comprised the study population. All patients
      underwent standard echocardiography at baseline and 3 months later for evaluation
      of RV systolic and diastolic function. At day 5 DSE was performed for evaluation
      of RV contractile reserve. Of the total number of segments analyzed, 69% were
      detected as stunned. At baseline, RV systolic and diastolic indices were
      seriously impaired showing significant improvement at follow-up. RV wall-motion
      score index during DSE was positively correlated with the same index at follow
      up. DSE is a safe and precise modality to predict recovery of stunned myocardium
      in the setting of RVI.

PMID- 15846164
TI  - Does transesophageal echocardiographic demonstration of a patent foramen ovale in
      patients with a recent cerebral ischemic event change anticoagulation therapy?
AB  - BACKGROUND: Patent foramen ovale (PFO) is commonly demonstrated by
      transesophageal echocardiography (TEE) in patients with a recent transient
      ischemic attack or stroke. Our purpose was to determine how the TEE visualization
      of a PFO alters anticoagulation therapy. METHODS: We retrospectively identified
      100 patients with transient ischemic attack or stroke referred for TEE; 50 had a
      PFO and 50 did not (control patients). RESULTS: Both groups were similar in
      regard to age, sex, the occurrence of transient ischemic attack versus stroke,
      and history of stroke. The PFO group had a higher incidence of a mobile
      interatrial septum, interatrial septal aneurysm, or both ( P < .001 by Fisher
      exact test). Both groups had similar pre-TEE aspirin, other antiplatelet, and
      warfarin use. After TEE, warfarin was instituted in 8 of 50 patients with PFO
      versus 2 of 50 in the control group ( P = .05) and aspirin use was discontinued
      in 9 of 50 patients with PFO versus 3 of 50 in the control group ( P = .12).
      CONCLUSION: The main effect of demonstrating a PFO by TEE after an ischemic
      cerebral event was the institution of warfarin; there was a trend toward
      discontinuing aspirin.

PMID- 15846165
TI  - Computer-based training in two-dimensional echocardiography using an
      echocardiography simulator.
AB  - Two-dimensional (2D) echocardiography is a user-dependent technique that poses
      some inherent problems to the beginner. The first problem for beginners is
      spatial orientation, especially the orientation of the scan plane in reference to
      the 3-dimensional (3D) geometry of the heart. The second problem for beginners is
      steering of the ultrasound probe. We have designed a simulator to teach these
      skills. On a computer screen a side-by-side presentation of a 3D virtual reality
      scene on the right side and a 2D echocardiographic view on the left side is
      given. The virtual scene consists of a 3D heart and an ultrasound probe with scan
      plane. The 2D echocardiographic image is calculated from 3D echocardiographic
      data sets that are registered with the heart model to achieve spatial and
      temporal congruency. The displayed 2D echocardiographic image is defined and
      controlled by the orientation of the virtual scan plane. To teach hand-eye
      coordination we equipped a dummy transducer with a 3D tracking system and placed
      it on a dummy torso. We have evaluated the usability of the simulator in an
      introductory course for final-year medical students. The simulator was graded
      realistic and easy to use. According to a subjective self-assessment by a
      standardized questionnaire the aforementioned skills were imparted effectively.

PMID- 15846166
TI  - The advantages of becoming a clinical site for ultrasound schools.
AB  - The field of echocardiography is facing critical staffing shortages. As the field
      continues to grow and practicing sonographers begin to retire, the need to
      produce more qualified sonographers is critical. In addition to job openings
      because of growth, some job openings will arise from the need to replace
      sonographers who leave the occupation permanently. One way echocardiographers can
      address this issue is to have their institutions become clinical sites for local
      accredited ultrasound schools.

PMID- 15846167
TI  - Right ventricular pre-ejection myocardial velocity and myocardial acceleration in
      normal fetuses assessed by Doppler tissue imaging.
AB  - Myocardial acceleration during isovolumic contraction obtained from Doppler
      tissue imaging has been introduced as an index of right ventricular contractile
      function that is unaffected by the shape of the ventricle and loading conditions,
      but normal value of myocardial acceleration during isovolumic contraction and the
      effect of aging on the index are not known in normal fetuses. We studied 61
      normal fetuses aged 20 to 39 weeks (29.8 +/- 5.1 weeks). Fetuses were divided
      into 4 age groups: 20 to 24 weeks (n = 11); 25 to 29 weeks (n = 20); 30 to 34
      weeks (n = 20); and 35 to 39 weeks (n = 10). Using Doppler tissue imaging, peak
      pre-ejection myocardial velocity was measured at the base of right ventricular
      free wall from 4-chamber view. Myocardial acceleration was calculated by dividing
      pre-ejection velocity by the time interval from onset of the pre-ejection
      myocardial velocity to the time at peak velocity of this wave. The mean pre
      ejection myocardial velocity was 5.0 +/- 1.1 cm/s. There was a stepwise increase
      in the pre-ejection myocardial velocity from the fetuses of 20 to 24 weeks to the
      fetuses of 35 to 39 weeks. The mean myocardial acceleration was 160 +/- 30 cm/s 2
      . The mean myocardial acceleration did not differ between the fetuses aged 20 to
      24 weeks (139 +/- 13 cm/s 2 ) and the fetuses aged 25 to 29 weeks (143 +/- 21
      cm/s 2 ), but after 30 weeks increased with gestational age. For the total group
      combining the 4 different gestational age groups, the pre-ejection myocardial
      velocity and myocardial acceleration correlated with gestational age ( r = 0.85
      and 0.75). This study demonstrated the gestational age-related changes in pre
      ejection myocardial velocity and myocardial acceleration. The load-independent
      index of contractility, myocardial acceleration, increased mainly after 30 weeks'
      gestation.

PMID- 15846168
TI  - Fetal Doppler echocardiographic diagnosis and successful steroid therapy of
      Luciani-Wenckebach phenomenon and endocardial fibroelastosis related to maternal
      anti-Ro and anti-La antibodies.
AB  - BACKGROUND: Complete fetal heart block (HB) and endocardial fibroelastosis (EFE)
      are known to be associated with maternal anti-Ro and anti-La antibodies. Complete
      fetal HB is irreversible. OBJECTIVES: We sought to (1) assess the value of the
      superior vena cava/ascending aorta Doppler approach in the early detection of
      abnormal delay in the fetal atrioventricular (AV) time of conduction, before
      appearance of complete fetal HB; and (2) report the effect of prenatal steroid
      therapy on EFE, HB, or both. RESULTS: The clinical history, echocardiographic,
      and Doppler investigations of 3 fetuses and children born to mothers positive for
      anti-Ro and anti-La antibodies are reported. Two fetuses presented with EFE
      either isolated (29 weeks) or associated with AV block (25 weeks). In this last
      case, the superior vena cava/ascending aorta approach allowed the identification
      of a Luciani-Wenckebach phenomenon. In a third fetus, 2:1 AV block was noted at
      23 weeks of gestation. Dexamethasone (4 mg/day) was administered to all 3
      patients. Complete regression of the EFE and conduction abnormalities was
      documented in all cases. CONCLUSION: Early prenatal detection of abnormal delay
      in fetal AV time conduction is possible with the Doppler superior vena
      cava/ascending aorta approach. Steroid therapy can cure fetal EFE and AV
      conduction delays associated with maternal anti-Ro and anti-La antibodies.

PMID- 15846169
TI  - Right ventricular outflow tract thrombus in a case of Behcet's disease.
AB  - Behcet's disease is known as a chronic systemic vasculitic syndrome, the hallmark
      of which is recurrent oral aphthous and genital ulcerations and uveitis. Vascular
      involvement, mainly thrombosis, reportedly affects as many as one-third of
      patients. Cardiac involvement, however, is very rare. We present in this report a
      young female patient developing right ventricular thrombus while being treated
      medically.

PMID- 15846170
TI  - Chloroquine-induced cardiomyopathy-echocardiographic features.
AB  - A 61-year-old woman with a 30-year history of systemic lupus erythematosus
      treated with chloroquine sulfate presented with complete heart block, congestive
      heart failure, and findings of restrictive cardiomyopathy on echocardiogram.
      Thickening of mitral, aortic, and tricuspid valves along with mild to moderate
      valve regurgitation was also present. Magnetic resonance imaging showed increased
      gadolinium uptake in the interventricular septum and the left ventricular lateral
      wall. Endomyocardial biopsy specimen showed marked myocardial cytoplasmic
      vacuolation and extensive myelin figures. Seven months after discontinuation of
      chloroquine, she showed significant clinical improvement and reversal of
      cardiomyopathy on echocardiography. This is the first case report describing a
      cardiomyopathy with prolonged use of chloroquine involving the conduction system,
      cardiac valves, and the myocardium with reversal on discontinuation of the drug.

PMID- 15846171
TI  - Gestational diabetes: the consequences of not treating.
AB  - OBJECTIVE: Untreated gestational diabetes mellitus carries significant risks of
      perinatal morbidity at all severity levels; treatment will enhance outcome. STUDY
      DESIGN: A matched control of 555 gravidas, gestational diabetes mellitus
      diagnosed after 37 weeks, were compared with 1110 subjects treated for
      gestational diabetes mellitus and 1110 nondiabetic subjects matched from the same
      delivery year for obesity, parity, ethnicity, and gestational age at delivery.
      The nondiabetic subjects and those not treated for gestational diabetes mellitus
      were matched for prenatal visits. RESULTS: A composite adverse outcome was 59%
      for untreated, 18% for treated, and 11% for nondiabetic subjects. A 2- to 4-fold
      increase in metabolic complications and macrosomia/large for gestational age was
      found in the untreated group with no difference between nondiabetic and treated
      subjects. Comparison of maternal size, parity, and disease severity revealed a 2-
      to 3-fold higher morbidity rate for the untreated groups, compared with the other
      groups. CONCLUSION: Untreated gestational diabetes mellitus carries significant
      risks for perinatal morbidity in all disease severity levels. Timely and
      effective treatment may substantially improve outcome.

PMID- 15846172
TI  - Beyond the pill: new data and options in hormonal and intrauterine contraception.
AB  - With the goal of helping clinicians facilitate contraceptive success for their
      patients, this Clinical Opinion provides an update regarding older hormonal and
      intrauterine contraceptives and details newer methods that include the progestin
      releasing intrauterine system, the contraceptive patch and ring, and extended and
      emergency oral contraception. Last, I will look over the horizon and briefly
      describe potential future methods that include the single rod progestin-releasing
      implant, folic acid-supplemented oral contraceptives, and hormonal contraception
      for men.

PMID- 15846173
TI  - Increased nuchal translucency with normal karyotype.
AB  - Increased fetal nuchal translucency (NT) thickness between 11 and 14 weeks'
      gestation is a common phenotypic expression of chromosomal abnormalities,
      including trisomy 21. However, even in the absence of aneuploidy, nuchal
      thickening is clinically relevant because it is associated with an increase in
      adverse perinatal outcome caused by a variety of fetal malformations, dysplasias,
      deformations, dysruptions, and genetic syndromes. Once the presence of aneuploidy
      is ruled out, the risk of perinatal outcome dose not statistically increase until
      the nuchal translucency measurement reaches 3.5 mm or more (>99th percentile).
      This increase in risk occurs in an exponential fashion as the NT measurement
      increases. However, if the fetus survives until midgestation, and if a targeted
      ultrasound at 20 to 22 weeks fails to reveal any abnormalities, the risk of an
      adverse perinatal outcome and postnatal developmental delay is not statistically
      increased.

PMID- 15846175
TI  - The interleukin-6--174 single nucleotide polymorphism: cervical protein
      production and the risk of preterm delivery.
AB  - OBJECTIVE: The purpose of this study was to determine the associations between
      preterm delivery (PTD), cervical fluid interleukin-6 (IL-6) concentration, and
      the single nucleotide polymorphism at position -174 in the IL-6 gene. STUDY
      DESIGN: Cervical fluid samples were obtained from women 23 to 32 weeks' gestation
      with symptoms of preterm labor. Concentrations of IL-6 were determined by enzyme
      linked immunosorbent assay (ELISA). IL-6 genotyping was performed using a
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      technique. RESULTS: One hundred thirty-seven women were enrolled, and complete
      information was available for 126. Cervical fluid IL-6 concentrations were not
      elevated in women destined to have a spontaneous PTD ( P = .86). IL-6 -174
      genotype was not associated with PTD ( P = .62) or cervical fluid IL-6
      concentration ( P = .36). Neonatal IL-6-174 genotype was not associated with PTD
      or IL-6 concentration. CONCLUSION: Cervical fluid concentrations of IL-6 were not
      elevated in symptomatic women destined to have a spontaneous PTD. The presence of
      maternal IL-6 -174C was not associated with cervical fluid concentration of IL-6
      or risk of PTD.

PMID- 15846176
TI  - Implantation of encapsulated glial cell line-derived neurotrophic factor
      secreting cells prevents long-lasting learning impairment following neonatal
      hypoxic-ischemic brain insult in rats.
AB  - OBJECTIVE: Implantation of encapsulated glial cell line-derived neurotrophic
      factor-secreting cells into brain parenchyma reduces histological brain damage
      following hypoxic-ischemic stress in neonatal rats. We examined the effect of
      glial cell line-derived neurotrophic factors on long-term learning and memory
      impairment and morphological changes up to 18 weeks after hypoxic-ischemic stress
      in neonatal rats. STUDY DESIGN: Baby hamster kidney cells were transfected with
      expression vector either including (glial cell line-derived neurotrophic factor
      hypoxic-ischemic group; n = 10) or not including (control-hypoxic-ischemic group;
      n = 8) human glial cell line-derived neurotrophic factor cDNA, encapsulated in
      semipermeable hollow fibers, and implanted into the left brain parenchyma of 7
      day-old Wistar rats. Two days after implantation the rats received hypoxic
      ischemic stress, and their behavior was then examined in several learning tasks:
      the 8-arm radial maze, choice reaction time, and water maze tasks, which examine
      short-term working memory, attention process, and long-term reference memory,
      respectively. The rats were killed 18 weeks after the hypoxic-ischemic insult for
      evaluation of brain damage. Two additional control groups were used: the control
      group (n = 15), which underwent no treatment, and the glial cell line-derived
      neurotrophic factor group (n = 6), which underwent implantation of the glial cell
      line-derived neurotrophic factor capsule but did not undergo hypoxic-ischemic
      stress. RESULTS: The decrease in the size of the cerebral hemisphere was
      significantly less in the glial cell line-derived neurotrophic factor-hypoxic
      ischemic group, compared with the control-hypoxic-ischemic group, and improved
      performance was observed in all three tasks for the glial cell line-derived
      neurotrophic factor-hypoxic-ischemic group: for the control-hypoxic-ischemic
      group versus the glial cell line-derived neurotrophic factor-hypoxic-ischemic
      group, respectively, in the 8-arm radial maze test, average number of correct
      choices was 6.2 +/- 0.1 versus 6.9 +/- 0.1 ( P < .01); in the choice reaction
      time test, average reaction time for a correct response was 2.35 +/- 0.1 seconds
      versus 1.97 +/- 0.09 seconds ( P < .01); in the water maze test, average swimming
      length was 1120.0 +/- 95.2 cm versus 841.6 +/- 92.1 cm ( P < .01). All results
      for the glial cell line-derived neurotrophic factor group were similar to those
      for the control group. CONCLUSION: Glial cell line-derived neurotrophic factor
      treatment is effective in not only reducing brain damage but also inhibiting
      learning and memory impairment, following hypoxic-ischemic insult in neonatal
      rats. No adverse effects in learning and memory tests were observed in the glial
      cell line-derived neurotrophic factor group.

PMID- 15846177
TI  - Preventive effect of recombinant human lactoferrin in a rabbit preterm delivery
      model.
AB  - OBJECTIVE: Lactoferrin, an iron-binding glycoprotein found in cervical mucus and
      amniotic fluid, plays a defensive role against mucosal infections. This study
      examined the effect of recombinant human lactoferrin on preterm delivery in a
      rabbit model. STUDY DESIGN: Anesthetized rabbits were randomly assigned to
      receive either inoculation with Escherichia coli or saline solution and to
      receive treatment with or without recombinant human lactoferrin inserted into the
      cervix 2 hours before bacterial inoculation (condition A: saline + saline;
      condition B: E coli + saline; condition C: E coli + recombinant human
      lactoferrin). E coli , saline solution, and recombinant human lactoferrin were
      inserted into the cervix using a hysteroscope and a sterile polyethylene cannula.
      Fetus survival rate and days to delivery after inoculation were monitored and
      tumor necrosis factor-alpha concentrations were measured in maternal serum and
      amniotic fluid. RESULTS: Fetus survival for conditions A, B, and C were 95.7%,
      0%, and 32.6%, respectively, whereas pregnancy continuation was 7.00 +/- 0 days,
      3.25 +/- 0.43 days, and 4.85 +/- 1.77 days, respectively. CONCLUSION: Cervical
      recombinant human lactoferrin administration increased fetal survival and
      extended pregnancy. Lactoferrin has an anti-inflammatory action as well as an
      antibacterial action, suggesting that recombinant human lactoferrin has the
      potential to prevent preterm delivery originating from cervical infection in the
      clinical setting.

PMID- 15846178
TI  - Tissue-specific engraftment after in utero transplantation of allogeneic
      mesenchymal stem cells into sheep fetuses.
AB  - OBJECTIVE: Mesenchymal stem cells (MSC) have multiorgan differentiation capacity,
      providing the potential for prenatal treatment of genetic disorders. We address
      the question if in utero transplantation of MSC results in short-term organ
      specific engraftment in the fetal sheep. STUDY DESIGN: Sheep fetal liver-derived
      MSC selected by adherence culture (passage 1) were transplantated into the fetal
      peritoneal cavity with ultrasound-guidance (mean gestational age, 59 days). After
      14 days recipient fetuses were analyzed by fluorescence-activated cell sorting
      (FACS), real-time polymerase chain reaction (PCR), and immunohistochemistry.
      RESULTS: Fetuses (n = 11) were transplanted with 7.7 x 10(6) MSCs (mean). All
      surviving fetuses (n = 5) showed engraftment with mean levels of 3.2% (lung),
      0.8% (spleen), 0.6% (liver, brain), 0.4% (bone marrow), 0.1% (blood, thymus), and
      <0.1% (kidneys) by flow cytometry. Immunohistochemistry showed organ-specific
      distribution. CONCLUSION: In utero transplantation of allogeneic MSC results in
      low level, multiorgan engraftment at 14 days post transplant. This supports the
      potential of in utero MSC transplantation for the treatment of nonhematopoietic
      genetic disorders of the fetus.

PMID- 15846179
TI  - Extracellular matrix changes in the umbilical arteries of growth-restricted
      fetuses.
AB  - OBJECTIVE: This study was undertaken to determine whether the expression of
      extracellular matrix components (ECM) is altered in the umbilical arteries from
      preterm fetal growth-restricted (FGR) pregnancies. STUDY DESIGN: Preterm
      pregnancies with FGR were compared with appropriately grown preterm pregnancies.
      Umbilical artery messenger RNA (mRNA) levels for fibrillar collagens I and III,
      nonfibrillar collagen XIV, and decorin were determined by using relative reverse
      transcriptase polymerase chain reaction (RT-PCR). The mRNA expression was
      compared between cases and controls by using the Student t test. P < or = .05 was
      considered significant. RESULTS: Eight FGR cases and 5 control pregnancies were
      analyzed. Mean counts per minute (cpm) +/- SEM for collagen I and collagen III
      were increased in FGR pregnancies. There were no differences in mRNA expression
      of collagen XIV or decorin. CONCLUSION: Increased mRNA expression of collagen I
      and III, but not collagen XIV or decorin, is found in the umbilical arteries of
      preterm FGR pregnancies.

PMID- 15846180
TI  - Does the presence of a funnel increase the risk of adverse perinatal outcome in a
      patient with a short cervix?
AB  - OBJECTIVE: This study was undertaken to determine whether the presence of a
      dilated internal os (funneling or beaking) alters the outcome of patients with a
      short cervix documented by transvaginal ultrasound in the second trimester. STUDY
      DESIGN: Between January 1998 and May 2004, all singleton pregnancies with a short
      cervix (< or =2.5 cm) and no funnel between 16 and 24 weeks' gestational age were
      identified by query and review of the Lehigh Valley Perinatal Ultrasound
      Database. These no funnel patients were compared with patients with a short
      cervix and funnel matched in accordance with cervical length and risk factors.
      Multiple variables of perinatal outcome were identified and compared between the
      Funnel and No Funnel groups. Correlations between cervical measurements and
      gestational age at birth were analyzed. RESULTS: Of the 279 patients with a short
      cervix identified, 82 were singleton with a T-shaped cervix and no funnel and 82
      patients matched with a typical Y-shaped funnel. There was no difference between
      groups with respect to maternal demographics, previous preterm birth (28.1% No
      Funnel group vs 36.5% Funnel group, P = .3), prior cervical surgery (24.3% vs
      22.0 %, P = .8), gestational age at entry (20.5 +/- 2.1 vs 21.1 +/- 2.4 weeks, P
      = .1), and cervical length (1.9 +/- 0.4 vs 1.8 +/- 0.5 cm , P = .1). The No
      Funnel group had significantly less readmissions for preterm labor (43.2% vs 67.1
      %, P = .004), chorioamnionitis (2.4% vs 23.2 %, P = .0002), abruption (1.2% vs
      13.4 %, P = .007), preterm rupture of membranes (6.1% vs 23.4%, P = .002), and
      cerclage placement (23.2% vs 43 %, P = .008). The neonates in the no funnel group
      delivered later (36.2% +/- 4.6 vs 33.8 +/- 5.4 weeks , P = .003), and had less
      morbidity and mortality (17.1% vs 37.8 %, P = .02) compared with the Funnel
      group. The width and depth of the funnel did not correlate with perinatal
      outcome. Cervical length ( R(2) = 0.07, P = .02) and cervical funneling as a
      categorical variable ( r = 0.3, P = .0002) did correlate with earlier delivery.
      CONCLUSION: The disruption of the internal os, as documented by funneling, is a
      significant risk factor for adverse perinatal outcome (ie, preterm labor,
      chorioamnionitis, abruption, rupture of the membranes, and serious neonatal
      morbidity and mortality). Cervical funneling is best measured as a categorical
      variable (present or absent).

PMID- 15846182
TI  - Sacrocolpopexy for vault prolapse and rectocele: do concomitant Burch
      colposuspension and perineal mesh detachment affect the outcome?
AB  - OBJECTIVE: This study compares the effect of abdominal sacrocolpopexy with
      posterior Teflon mesh interposition with and without concomitant Burch
      colposuspension on the posterior compartment. STUDY DESIGN: This retrospective
      review includes 49 consecutive women who underwent sacrocolpopexy for vault or
      uterine prolapse stage 2 or higher and rectocele; 25 of them had a concomitant
      Burch colposuspension for urodynamic stress incontinence. Postoperative bladder,
      bowel and sexual function and recurrent pelvic organ prolapse was assessed at >
      or =12 months. RESULTS: There was no recurrent vault prolapse. Rectoceles (stage
      2) recurred in 5 women (21%) without and in 8 women (36%) with Burch
      colposuspension ( P > .05). The mesh became detached by >2 cm from its perineal
      position in 30% of the cases, which was associated with excessive defecation
      straining ( P = .04). Rectocele stages significantly correlated with mesh
      detachment ( P > .001) but not with obstructed defecation ( P > .05). CONCLUSION:
      Sacrocolpopexy was effective if the mesh did not become detached from its
      perineal position. Concomitant Burch colposuspension did not seem to affect the
      posterior compartment adversely in this small case series.

PMID- 15846183
TI  - Specific serologic response to genital human papillomavirus types in patients
      with vulvar precancerous and cancerous lesions.
AB  - OBJECTIVE: Antibodies to human papillomavirus are indicative for previous human
      papillomavirus exposure. Human papillomavirus antibody reactivities to vulvar
      precancerous lesions were reported poorly, and the role of human papillomavirus
      in some of these lesions is still unclear. STUDY DESIGN: In a direct enzyme
      linked immunosorbent assay, serum samples from 126 healthy control subjects, 97
      women with lichen sclerosus with or without squamous hyperplasia, 78 women with
      vulvar intraepithelial neoplasia, and 16 women with verrucous carcinoma were
      examined for immunoglobulin G and A antibodies to L1 virus-like particles of
      genital human papillomavirus types 6, 11, 16, 18, and 31, cutaneous human
      papillomavirus type 8, bovine papilloma virus, and cottontail rabbit papilloma
      virus. RESULTS: In lichen sclerosus/squamous hyperplasia with atypia
      immunoglobulin G and A, antibody positivity rates to high-risk human
      papillomavirus virus-like particle types 16, 18, and 31 were significantly higher
      than in the control group and the lichen sclerosus/squamous hyperplasia group
      without atypia. In patients with vulvar intraepithelial neoplasia I, increased
      immunoglobulin G antibody prevalences with both high-risk and low-risk human
      papillomavirus-virus-like particles were detected; whereas in patients with
      vulvar intraepithelial neoplasia II/III, this was observed only with the human
      papillomavirus types 16, 18, and 31. When only reactivities with 2 genital human
      papillomavirus types were compared, percentages of positives to only 1 of these 2
      types ranged between 43% and 82%, with regard to all respective positives.
      CONCLUSION: Our data support the role of high-risk human papillomavirus types,
      mainly human papillomavirus-16, in the pathogenesis of different vulvar lesions
      with atypia. Serologically, there are no indications that lichen
      sclerosus/squamous hyperplasia without atypia is associated with human
      papillomavirus, but high-risk human papillomavirus in lichen sclerosus/squamous
      hyperplasia with atypia could play a role in carcinogenesis. High antibody
      specificity was clearly demonstrated among 5 genital, 1 cutaneous human, and 2
      animal papillomavirus types.

PMID- 15846184
TI  - Papanicolaou screening in an urgent care setting.
AB  - OBJECTIVE: This study was undertaken to determine the efficacy of Papanicolaou
      (Pap) screening in an urgent care setting, and to compare the rates of cervical
      intraepithelial neoplasia (CIN), and follow-up in patients with and without
      established primary care. STUDY DESIGN: All patients presenting with a complaint
      warranting pelvic examination between December 2000 and September 2001 underwent
      Pap screening. All patients were scheduled an appointment or follow-up visit when
      an abnormal Pap test was found. Charts were reviewed for cytologic
      interpretation, age, chief complaint, ethnicity, history of prior Pap smear in
      the institution, total visit history (includes urgent care and primary care
      clinics). SAS 8.1 was used for statistical analysis with the use of the Fisher
      exact test. RESULTS: A total of 673 Pap smears were performed. Of those, 660 were
      analyzed and 13 were discarded because of inadequate slides. The mean age was
      29.6 years; the ethnic distribution was 0.2% Native American, 1.2% Asian, 17%
      black, 62.4% Hispanic, 18.2% white, and 1.1% other. In the study population, only
      40.6% of the patients had a prior Pap screen and 59.4% had not. There were 318
      (48.2%) patients who had accessed care only through the urgent care clinic, and
      342 (51.8%) patients who had established some kind of primary care in the past.
      The overall follow-up rate was 56% for any abnormal Pap smear, regardless of
      visit history. CONCLUSION: Patients accessing medical care through an urgent care
      clinic exclusively had identical rates of CIN and follow-up when compared with
      patients with established care. Therefore, when a system exists to centrally
      process and triage cervical cytology, it is efficacious to screen for CIN in an
      urgent care setting.

PMID- 15846185
TI  - The effects of C161-->T polymorphisms in exon 6 of peroxisome proliferator
      activated receptor-gamma gene on bone mineral metabolism and serum
      osteoprotegerin levels in healthy middle-aged women.
AB  - OBJECTIVE: We evaluated the association of different genotypes in C161-->T
      substitution in exon 6 of peroxisome proliferator-activated receptor-gamma
      (PPARgamma) gene with bone turnover markers, bone mineral density (BMD), and
      serum osteoprotegerin (OPG) in female subjects to reveal the role of PPARgamma in
      bone. STUDY DESIGN: In 263 healthy Korean women (mean age 52 years),
      anthropometric measurements were taken along with measurements of lumbar spine
      and femoral neck BMD, bone turnover markers, such as alkaline phosphatase, serum
      calcium, phosphorus, 24-hour urine calcium, phosphorus excretion, and urine
      deoxypyridinoline. Serum follicular stimulating hormone levels were measured and
      serum OPG levels were measured with the enzyme-linked immunosorbent assay method.
      Polymerase chain reaction-restriction fragment length polymorphism was performed.
      RESULTS: Allele frequencies were 0.804 for the C allele and 0.196 for the T
      allele. There were no differences in mean age, body mass index, BMD, and bone
      turnover markers among different genotypes, and the subjects with T alleles had
      significantly lower serum OPG levels. There were no differences in the prevalence
      of metabolic bone diseases according to the genotypes. When analyzed according to
      the menopausal status, only postmenopausal subjects with T alleles showed
      significantly lower serum OPG levels. CONCLUSION: The frequencies of C161-->T
      substitution in exon 6 of the PPARgamma gene in Korean females were similar to
      other races and women with T alleles showed significantly lower serum OPG levels
      and it was especially noted for postmenopausal subjects, which supports the
      possible concurrent association of PPARgamma and OPG with estrogen status in
      female subjects.

PMID- 15846186
TI  - Tying a loop-to-strand suture: is it safe?
AB  - OBJECTIVE: This study was undertaken to evaluate the integrity of the loop-to
      strand knot when tied with square and nonidentical sliding knots. STUDY DESIGN:
      The synthetic absorbable monofilament suture poliglecaprone 25 in 0 and 2-0
      suture gauges was used in this experiment. For each suture gauge, 3 groups of
      knots were tested: (1) single strand-to-single strand, flat square knot, (2) loop
      to-single strand, flat square knot, and (3) loop-to-single strand, nonidentical
      sliding knot. All knots were tied with 6 throws. The proportion of knots becoming
      untied was compared among the 3 groups for each suture gauge. Ultimate load
      required to untie or break knots within each group was also evaluated. RESULTS:
      The loop-to-strand knot performed well in both suture gauges tested as long as it
      was tied with a flat square knot. The loop-to-strand knot tied with a
      nonidentical sliding knot had an unacceptably high failure rate. CONCLUSION: The
      loop-to-strand termination of a continuous suture may be acceptable when tied
      with a 6-throw flat square knot but not acceptable if tied with sliding knots.

PMID- 15846187
TI  - Safety of influenza vaccination during pregnancy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the safety of influenza
      vaccine that is administered in the second or third trimester of gestation. STUDY
      DESIGN: A retrospective electronic database search of 5 influenza seasons (July
      1, 1998, to June 30, 2003) was performed at a large multispecialty clinic in
      Houston, Texas. Immunization rates were calculated, and outcomes of pregnancy
      were compared between a cohort of healthy women who received influenza vaccine
      and a control group of healthy unvaccinated women who were matched by age, month
      of delivery, and type of medical insurance. RESULTS: Among 7183 eligible mother
      infant pairs, only 252 pregnant women (3.5%) received the influenza vaccine.
      Women with medical insurance were more likely to be vaccinated, although the
      rates for women with chronic underlying conditions were similar to those of
      healthy women, regardless of insurance status. The mean gestational age at the
      time of influenza vaccination was 26.1 weeks (range, 14-39 weeks). No serious
      adverse events occurred within 42 days of vaccination, and there was no
      difference between the groups in the outcomes of pregnancy (including cesarean
      delivery and premature delivery) and infant medical conditions from birth to 6
      months of age. CONCLUSION: Influenza vaccine that was administered in the second
      or third trimester of gestation was safe in this study population.

PMID- 15846188
TI  - First-trimester screening for trisomy-21 using a simplified method to assess the
      presence or absence of the fetal nasal bone.
AB  - OBJECTIVE: To determine the benefit of including nasal bone assessment in
      addition to standard first-trimester markers (nuchal translucency, free beta
      human chorionic gonadotropin and pregnancy-associated plasma protein A) as a
      screening test for Down syndrome, using a strict criterion for classification of
      nasal bone absence. STUDY DESIGN: Nasal bone assessment was conducted in 2411
      patients with crown-rump length between 45 and 84 mm, including 15 patients with
      Down syndrome. A patient was considered to have an absent nasal bone only if
      there was no evidence of present nasal bone. Unlike other studies, nasal bone was
      classified as present when there was evidence of a thin echogenic line under the
      skin. Simulation studies were conducted to assess the detection rate and false
      positive rate of a combined first-trimester screening protocol including nasal
      bone assessment. RESULTS: There were 9 of 2396 (0.4%) unaffected cases with
      absent nasal bone (95% confidence interval 0.2%, 0.7%) and 8 of 15 (53.3%) Down
      syndrome cases (95% confidence interval 26.6%, 78.7%). Using a 1 in 250 risk cut
      off, the detection rate of standard first-trimester screening was 87%, with a
      false-positive rate of 4.3%. Incorporating nasal bone measurement improved the
      detection rate of Down syndrome to 90% and reduced the false-positive rate to
      2.5%. CONCLUSION: The use of a strict criterion to determine nasal bone absence
      leads to fewer cases classified as absent and may simplify the implementation of
      nasal bone as a marker for first-trimester screening, resulting in lower false
      positives and higher detection, compared with other current screening protocols.

PMID- 15846189
TI  - Individual placental territories after selective laser photocoagulation of
      communicating vessels in twin-twin transfusion syndrome.
AB  - OBJECTIVE: Intrauterine fetal death of one or both twins after laser therapy
      (selective photocoagulation of communicating vessels) may occur, in part, from
      insufficient individual placental mass. The objective of this study was to assess
      the percentage of individual placental mass (individual placental territory) that
      is associated with fetal survival in twin-twin transfusion syndrome after
      selective photocoagulation of communicating vessels. STUDY DESIGN: Placentas from
      72 patients with selective photocoagulation of communicating vessels-treated twin
      twin transfusion syndrome without intrauterine fetal death and from 61
      monochorionic pregnancies without twin-twin transfusion syndrome (control
      subjects) were assessed. The placentas were weighed fresh (total placental mass)
      and cut along the vascular equator, which yielded the individual placental mass
      and the individual placental territory. Patency of anastomoses was ruled out with
      air-injection. The individual fetoplacental ratio was obtained by dividing birth
      weight by the corresponding individual placental mass. RESULTS: The 5th
      percentile individual placental territory that was associated with fetal survival
      was 27% in control subjects and 18% in cases with twin-twin transfusion syndrome,
      with a minimum of 10% to 14%, respectively. There were no differences in total
      placental mass, individual placental mass, individual placental territory, or
      individual fetoplacental ratio between pregnancies with twin-twin transfusion
      syndrome and control subjects. However, corrected for gestational age, the birth
      weight of recipient and donor twins were significantly smaller than control
      subjects. The individual placental territory of donors was statistically smaller
      than that of recipients. Individual placental territories were not different
      within control subjects. CONCLUSION: Fetal survival typically is associated with
      at least 18% of individual placental territory after selective photocoagulation
      of communicating vessels for twin-twin transfusion syndrome, but it can occur
      with as little as 10% to 14% individual placental territory. Decreased birth
      weight of the donor twin could result from relative decreased percentage of
      individual placental territory or from the loss of nutrients to the recipient
      twin. Decreased birth weight of the recipient twin could result from partial
      deprivation of functional placental tissue after surgery. Our findings may
      contribute to the understanding of normal and pathologic monochorionic twin
      gestations, in the counseling of patients, and potentially to the improvement of
      surgical treatment of twin-twin transfusion syndrome.

PMID- 15846190
TI  - Should we offer expectant management in cases of severe preterm preeclampsia with
      fetal growth restriction?
AB  - OBJECTIVE: The purpose of this study was to assess maternal and fetal morbidity
      and death in cases of severe preterm preeclampsia that were managed expectantly.
      STUDY DESIGN: It is a retrospective study that included 155 singleton pregnancies
      with severe preeclampsia at <34 weeks of gestation that were managed expectantly
      over a 10-year period. Perinatal outcomes of both mother and fetus were
      stratified according to gestational age and the severity of fetal growth
      restriction < or =3th percentile, 4th to 5th percentile, >5th to10th percentile,
      and >10th percentile. RESULTS: The mean gestational age at admission was 30.2 +/-
      2.4 weeks (range, 23.9-34.0 weeks). The mean latency period was 5.3 +/- 5.2 days,
      with a perinatal mortality rate of 3.9%. Gestational age of <30 weeks of
      gestation was the strongest variable that affected perinatal outcome, whereas
      fetal growth restriction played a marginal role. CONCLUSION: Expectant management
      is recommended strongly in fetuses at <30 weeks of gestation, irrespective of
      fetal growth restriction. Delivery should be considered at >30 weeks of
      gestation.

PMID- 15846192
TI  - Maternal preconceptional weight and gestational length.
AB  - Recent animal studies suggest that preconceptional undernutrition shortens
      gestation. We retested this idea among rural Gambian women who experience annual
      fluctuations in energy balance caused by the rains (with lowest weights in
      September to November) using records from 1918 infants. Pregnancies conceived in
      September to November were significantly shorter than those from better-fed
      months (38.6 vs 39.0 weeks; log-rank chi 2 = 17.4, P < .0001).

PMID- 15846191
TI  - Randomized trial of a physician-based intervention to increase the use of folic
      acid supplements among women.
AB  - OBJECTIVE: Fewer than one third of American women take folic acid daily, although
      many women report that they would take folic acid if their physicians advised
      them to do so. This study determined the impact of a physician intervention
      during routine gynecologic visits on folic acid supplementation. STUDY DESIGN:
      Patients were assigned randomly to receive brief folic acid counseling, a
      reminder phone call, and 30 folic acid tablets (n = 162 women; intervention
      group) or to receive counseling about other preventive health behaviors and a
      folic acid informational pamphlet (n = 160 women; control group). Self-reported
      folic acid use was compared at baseline and at 2 months. RESULTS: Of the 279
      patients who completed the study, weekly folic acid intake increased in the
      intervention group by 68%, compared with 20% in the control group ( P =.008). No
      significant differences were found in daily intake. The women who were most
      influenced by the intervention were black and lower income and not planning
      pregnancies. CONCLUSION: With little effort expended to encourage folic acid use,
      gynecologists could potentially reduce the risk of folate-preventable birth
      defects among their patients by as much as 11%.

PMID- 15846193
TI  - Grafting of glial cell line-derived neurotrophic factor secreting cells for
      hypoxic-ischemic encephalopathy in neonatal rats.
AB  - OBJECTIVE: It has been reported that an infarcted area is reduced by the
      injection of glial cell line-derived neurotrophic factor into brain parenchyma
      after hypoxic/ischemic insult in neonatal rats. For use of glial cell line
      derived neurotrophic factor in humans, we have developed a system for the
      delivery of a constant supply of glial cell line-derived neurotrophic factor to
      the brain. The aim of this study was to examine the neuroprotective effect of
      glial cell line-derived neurotrophic factor with the use of this delivery system.
      STUDY DESIGN: Baby hamster kidney cells were transfected with human glial cell
      line-derived neurotrophic factor complementary DNA, encapsulated in semipermeable
      hollow fibers, and implanted into the left cerebrum of 12-day-old Wistar rats
      (glial cell line-derived neurotrophic factor group, 11 rats). Nontransfected baby
      hamster kidney cells served as controls (control group, 9 rats). Two days after
      implantation, the rats received a hypoxic/ischemic stress, with a modification of
      Levine's method. Seven days later the rats were killed, and coronal brain slices
      were cut 2, 4, 6, 8, and 10 mm from the anterior pole. The cortex, hippocampus,
      striatum, and thalamus were evaluated for damage severity. The serum
      concentrations of glial cell line-derived neurotrophic factor were also
      determined. RESULTS: The left brain hemispheric area was significantly larger;
      the neuronal damage to each brain region was significantly less, and the serum
      glial cell line-derived neurotrophic factor concentrations were significantly
      higher in the glial cell line-derived neurotrophic factor group, compared with
      the control group. CONCLUSION: Grafting of encapsulated glial cell line-derived
      neurotrophic factor-secreting cells is a promising way to protect the neonatal
      brain from hypoxic/ischemic insult.

PMID- 15846194
TI  - Structural evidence for mechanisms to redistribute hepatic and ductus venosus
      blood flows in nonhuman primate fetuses.
AB  - OBJECTIVE: The ductus venosus (DV) and the intrahepatic branches of the portal
      vein (BPV) play an important role in umbilical blood distribution to the fetal
      liver and the rest of the fetal circulation. Increased DV shunting is a major
      fetal survival mechanism during stress situations. The availability of a
      nonpregnant primate animal model with similar structure and function would
      greatly improve our understanding of DV function. However, the anatomic and
      histologic structure of the DV and the BPV have not been thoroughly investigated
      in any nonhuman primate species. METHODS: Anatomic and immunohistochemical
      (Masson's and alpha-smooth actin stains) investigations were performed on 17
      baboon fetuses at 173 +/- 5 days' gestation (mean +/- SEM, term = 180 days)
      (Papio sp. ) and 3 near term rhesus (Macaca mulatta) fetuses. RESULTS: In both
      species the branchless, funnel-shaped DV coursed cranially, posteriorly, and
      slightly oblique to the left side. The DV and the efferent hepatic veins drained
      into a dilated ampullary area (the collectus venosus) that joined directly with
      the inferior cava. The length of the DV in baboons increased with gestational age
      ( r = 0.86, n = 16). In 4 baboon fetuses, we observed an asymmetrical muscular
      lip at the isthmic portion of the DV. The media of intrahepatic BPV contained
      more smooth muscle cells than the media of the DV. CONCLUSION: In nonhuman
      primate fetuses, the DV drains into a dilated ampullary area. An asymmetrical
      muscular lip forms a contractile element of the isthmic portion of the DV. The
      increased thickness of smooth muscle tissue in the DV isthmus and intrahepatic
      BPV in nonhuman primate fetuses support the concept of a general organization of
      a contractile apparatus that performs a sphincter-like function in the central
      venous hepatic system and plays a key role in blood flow redistribution.

PMID- 15846195
TI  - Routine hepatitis C virus screening in pregnancy: a cost-effectiveness analysis.
AB  - OBJECTIVE: The purpose of this study was to determine whether routine hepatitis C
      virus screening in pregnancy is cost-effective. STUDY DESIGN: A decision tree
      with Markov analysis was developed to compare 3 approaches to asymptomatic
      hepatitis C virus infection in low-risk pregnant women: (1) no hepatitis C virus
      screening, (2) hepatitis C virus screening and subsequent treatment for
      progressive disease, and (3) hepatitis C virus screening, subsequent treatment
      for progressive disease, and elective cesarean delivery to avert perinatal
      transmission. Lifetime costs and quality-adjusted life years were evaluated for
      mother and child. RESULTS: In our base case, hepatitis C virus screening and
      subsequent treatment of progressive disease was dominated (more costly and less
      effective) by no screening, with an incremental cost of 108 US dollars and a
      decreased incremental effectiveness of 0.00011 quality-adjusted life years. When
      compared with no screening, the marginal cost and effectiveness of screening,
      treatment, and cesarean delivery was 117 US dollars and 0.00010 quality-adjusted
      life years, respectively, which yields a cost-effectiveness ratio of 1,170,000 US
      dollars per quality-adjusted life year. CONCLUSION: The screening of asymptomatic
      pregnant women for hepatitis C virus infection is not cost-effective.

PMID- 15846196
TI  - Chorioamnionitis increases neonatal morbidity in pregnancies complicated by
      preterm premature rupture of membranes.
AB  - OBJECTIVE: To compare morbidities of neonates born to women who developed
      chorioamnionitis after premature preterm rupture of membranes versus those who
      did not. STUDY DESIGN: We reviewed outcomes in singleton pregnancies with
      confirmed premature preterm rupture of membranes at 24 weeks or beyond that
      resulted in delivery less than 37 weeks. Management of premature preterm rupture
      of membranes included the use of antibiotics, betamethasone if less than 32
      weeks, and expectant management with induction at 34 weeks or greater. Composite
      neonatal major and minor morbidity rates were compared between pregnancies
      complicated by chorioamnionitis and those that were not. RESULTS: From August
      1998 to August 2000, 430 cases of premature preterm rupture of membranes were
      identified among 6003 deliveries (7.2%). Thirteen percent of women (56/430) with
      premature preterm rupture of membranes developed chorioamnionitis. The incidence
      of chorioamnionitis increased significantly with decreasing gestational age. The
      composite neonatal major morbidity rate was significantly higher in neonates
      whose mothers developed chorioamnionitis (55%) versus those who did not (18%, P <
      .0001). In a multiple logistic regression model, chorioamnionitis ( P < .0001),
      infant gender ( P = .007), latency ( P = .03), and gestational age at delivery (
      P < .0001) were significantly associated with composite neonatal morbidity.
      CONCLUSION: Neonatal morbidities are significantly higher among pregnancies with
      premature preterm rupture of membranes complicated by chorioamnionitis when
      compared with pregnancies that were not.

PMID- 15846197
TI  - No increase in rates of early-onset neonatal sepsis by antibiotic-resistant group
      B Streptococcus in the era of intrapartum antibiotic prophylaxis.
AB  - OBJECTIVE: The aim of this study was to assess the rate of early-onset neonatal
      sepsis by antibiotic-resistant group B Streptococcus. STUDY DESIGN: The time
      trend study was conducted at a tertiary care center over the following periods:
      no protocol for group B Streptococcus prophylaxis (1990 to 1992), risk-based
      protocol (1993 to 1996), and screening-based protocol (1997 to 2002). RESULTS: A
      total of 120,952 neonates were born with 118 cases of group B Streptococcus early
      onset neonatal sepsis. The rate of group B Streptococcus early-onset neonatal
      sepsis decreased significantly (from 2.0 to 1.1 to 0.4 per 1000 births, P <
      .0001). No group B Streptococcus isolate was resistant to ampicillin, penicillin,
      cefazolin, or vancomycin. From 1997 to 2002, there were 3 clindamycin-resistant
      group B Streptococcus isolates (14%). The rate of erythromycin-resistant group B
      Streptococcus early-onset neonatal sepsis did not change (from 0.14 to 0.03 to
      0.08 per 1000 births, P = .6). However, cases of erythromycin-resistant group B
      Streptococcus early-onset neonatal sepsis accounted for an increasing proportion
      of the remaining cases of group B Streptococcus early-onset neonatal sepsis (from
      7.0% to 2.6% to 23.8%, P = .07). CONCLUSION: We found no increase in rates of
      antibiotic-resistant group B Streptococcus early-onset neonatal sepsis.

PMID- 15846198
TI  - Inflammation increases vulnerability to hypoxia in newborn piglets: effect of
      reoxygenation with 21% and 100% O2.
AB  - OBJECTIVE: The purpose of this study was to assess whether inflammation increases
      vulnerability to hypoxia, and influences the effect of 100% O(2) and 21% O 2
      reoxygenation on brain. STUDY DESIGN: Newborn piglets (n = 31) were randomized to
      4 interventional groups: pretreatment with saline or endotoxin. After hypoxia
      they were reoxygenated with 21% or 100% oxygen for 30 minutes, followed by 21%
      oxygen for all groups. To assess brain injury we measured extracellular brain
      tissue glucose, glycerol, and lactate/pyruvate by microdialysis, brain tissue
      oxygen tension, and laser Doppler flow. RESULTS: Administration of endotoxin
      reduced the time to reach base excess (BE) -20 mmol/L by median 32 minutes
      compared with saline ( P < .05). We found no differences in changes in
      biochemical markers, brain tissue microcirculation, or oxygen tension between
      piglets in the 4 groups. CONCLUSION: Endotoxin and hypoxia acted synergistically
      in inducing metabolic acidosis. In the presence of experimental inflammation, 21%
      oxygen seems as effective as 100% O(2) in reoxygenating piglets.

PMID- 15846199
TI  - Experimental intrauterine Ureaplasma infection in sheep.
AB  - OBJECTIVE: Prenatal Ureaplasma spp exposure is associated with preterm birth and
      modulates the neonates' susceptibility to respiratory distress syndrome and
      bronchopulmonary dysplasia. We hypothesized that intra-amniotic ureaplasmas would
      cause lung inflammation and alter fetal lung development. STUDY DESIGN: Pregnant
      ewes bearing singleton fetuses were given an intra-amniotic injection of 20 x 10
      6 CFUs of U parvum (serovar 3) or vehicle, either 1, 3, 6, or 10 weeks before the
      delivery of preterm lambs at 124 days of gestation (n = 4-10 per group) for
      evaluation of inflammation and fetal lung maturation. RESULTS: Ureaplasmas were
      recovered from amniotic and fetal lung fluids after intra-amniotic injection.
      Body weight and umbilical arterial pH were reduced by Ureaplasma exposure for 10
      weeks ( P < .05). Ureaplasmas caused progressive lung inflammation and
      improvements in lung function that were associated with increased surfactant
      lipids (control, 0.13 +/- 0.02 micromol/kg; 10 weeks of Ureaplasma exposure, 7.43
      +/- 3.0 micromol/kg; P < .001) and surfactant protein messenger RNA expression.
      CONCLUSION: Long-term exposure to ureaplasmas in amniotic fluid alters ovine
      fetal development.

PMID- 15846201
TI  - Of disparities and diversity: where are we?
AB  - There has been remarkable improvement in the health of women over the past
      century; however, disparities among minority populations persist. While the
      reasons for the disparities, usually poorer health, are many and complex, such
      disparities are unacceptable. Because the reasons for disparities are multiple
      and complex, eliminating health disparities will require a multifaceted approach.
      Increasing research into health disparities, biologic, sociologic, and health
      services research, transforming the health care system into a culturally
      sensitive system, eliminating unequal treatment provided to minority populations,
      increasing diversity in the health care workforce, and assuring that health care
      providers provide culturally competent health care are needed.

PMID- 15846202
TI  - Programmed syndrome of hypernatremic hypertension in ovine twin lambs.
AB  - OBJECTIVE: An increased risk of adult hypertension, obesity, and coronary heart
      disease occurs in low birth weight or intrauterine growth-restricted newborn
      infants as a result of fetal programming. Human twins represent a natural model
      of low birth weight and intrauterine growth restriction because they are
      significantly smaller at birth than singleton infants because of both earlier
      delivery and reduced intrauterine growth. Increased blood pressure has been
      reported in several epidemiologic studies of human twin offspring, although this
      has not been confirmed in an animal model. Because the sheep pregnancy consists
      of singleton and twin litters, we sought to determine the impact of ovine twin
      gestation and twin nursing on the cardiovascular and renal function of the
      offspring. STUDY DESIGN: Newborn lambs (n = 12) were studied at 21 +/- 2 day of
      life. Both singleton (n = 6) and twin lambs (n = 6) were born to ewes provided ad
      libitum water and food throughout gestation. After the delivery, ewes were
      provided ad libitum water and food, and newborn lambs were allowed ad libitum
      nursing with the maternal ewe. At 15 +/- 2 days of age, the lambs were prepared
      with vascular and renal catheters and studied at 21 +/- 2 days. After a 2-hour
      basal period, lambs received an intravenous infusion of hypotonic (0.075 mol/L)
      NaCl (0.15 ml/kg/hr) for an additional 2 hours. Newborn arterial blood pressure,
      heart rate, and urine flow were monitored continuously, and arterial blood
      samples were obtained before, during, and after the infusion. RESULTS: At birth,
      twin lambs weighed 30% less than singleton lambs (3.5 +/- 0.1 kg vs 5.0 +/- 0.2
      kg; P < .05), although 50% less at 21 days (5.2 +/- 0.6 vs 10.8 +/- 1.2 kg).
      There were marked differences in basal arterial blood values between twin and
      singleton lambs at 21 days, with twins having significantly increased plasma
      sodium and systolic, diastolic, and mean arterial pressures and reduced
      glomerular filtration rates, urine osmolality, osmolar excretion, and osmolar
      clearance (per kg body weight) compared with singleton lambs. In response to
      hypotonic saline solution infusion, the plasma composition and blood pressure
      differences between twin and singleton lambs persisted. CONCLUSION: These results
      indicate that ovine twin gestation and nursing markedly reduced body weight at 21
      days of age, with evidence of plasma hypernatremia, hypertension, and reduced
      glomerular filtration rates, which persisted throughout hypotonic saline solution
      infusion. Consistent with epidemiologic studies of humans, these results
      demonstrate that gestational/newborn nutrient stress may program hypertension in
      offspring.

PMID- 15846203
TI  - Fetal cheek-to-cheek diameter in the prediction of mode of delivery.
AB  - OBJECTIVE: The purpose of this study was to assess sonographic fetal cheek-to
      cheek diameter (CCD) in predicting mode of delivery. STUDY DESIGN: Two hundred
      sixty-four patients were considered in 2 parts. First, a retrospective analysis
      of 214 patients entered into a birth weight (BW) study. Measurements of the CCD,
      biparietal diameter (BPD), and BW, as well as labor data, were collected. Then a
      prospective study of patients at > or =38 weeks gestational age was conducted.
      Fetal weight (EFW) was estimated by routine measurements. Information regarding
      CCD was withheld from the delivering caregiver. Labor records were reviewed for
      BW and complications, defined as: instrumental delivery, cesarean section (C/S)
      for nonprogress of labor or "CPD," and "difficult" vaginal delivery. The CCD, BW
      (both parts), or EFW (prospective part) and mode of delivery were compared.
      RESULTS: Abnormal CCD (>2SD above previously published norms for each GA) was
      closely associated with cesarean delivery, regardless of EFW. At term, risk of
      C/S with a CCD >7.9 cm was 94%. CONCLUSION: Within limits, EFW alone has weak
      correlation with cesarean delivery. CCD, as a reflector of fetal adipose tissue,
      performs as well as actual BW and demonstrates good prediction for delivery by
      C/S.

PMID- 15846205
TI  - The role of ultrasound evaluation in the detection of early-stage epithelial
      ovarian cancer.
AB  - OBJECTIVE: Epithelial ovarian cancer kills more women than all other gynecologic
      malignancies combined because of our inability to detect early-stage disease.
      Ultrasonography has demonstrated usefulness in the detection of ovarian cancer in
      asymptomatic women, but its value for the detection of early-stage epithelial
      ovarian cancer in women of increased risk is uncertain. We examined the
      usefulness of sonography in the detection of early-stage epithelial ovarian
      cancer in asymptomatic high-risk women who participated in the National Ovarian
      Cancer Early Detection Program. STUDY DESIGN: Only asymptomatic women of
      increased risk for the development of ovarian cancer with initial normal
      gynecologic and ultrasound examinations were eligible to participate in the
      institutional review board-approved National Ovarian Cancer Early Detection
      Program. Participants underwent comprehensive gynecologic and ultrasound
      examinations every 6 months. Increased risk includes women with at least 1
      affected first-degree relative with ovarian cancer; a personal history of breast,
      ovarian, or colon cancer; > or =1 affected first- and second-degree relatives
      with breast and or ovarian cancer; inheritance of a breast cancer mutation from
      an affected family member, or membership within a recognized cancer syndrome.
      RESULTS: The average age of the 4526 women who were evaluated was 46 years; 2610
      women were premenopausal, and 1916 women were postmenopausal. A total of 12,709
      scans have been performed since 1990. Visualization of both ovaries was noted in
      98% of premenopausal and in 94% of postmenopausal women. Fourteen women had
      undergone unilateral salpingo-oophorectomy. Recall rates at less than the routine
      6-month interval were 0.4% in the premenopausal and 0.3% in postmenopausal women.
      A total of 98 women with persistent adnexal masses were identified, and 49
      invasive surgical procedures were performed that diagnosed 37 benign ovarian
      tumors and 12 gynecologic malignancies. All cancers were detected in asymptomatic
      women who had normal ultrasound and physical examinations 12 and 6 months before
      the cancer diagnosis. The detected malignancies were fallopian tube carcinoma
      (stage IIIC; n = 4 women), primary peritoneal carcinoma (n = 4 women; stage IIIA,
      1 woman; stage IIIB, 2 women; stage IIIC, 1 woman), epithelial ovarian cancer
      (stages IIIA and IIIB; n = 2 women), and endometrial adenocarcinoma (stage IA; n
      = 2 women). Additionally 37 primary and 12 recurrent breast carcinomas were
      detected by physical examination. A total of 184 women with genetic
      predisposition (breast cancer positive) have undergone a prophylactic bilateral
      salpingo-oophorectomy; 23% of these procedures found atypical hyperplasia, and
      unexpectedly, 2 women (1%) were found to have stage III (A and B) primary
      peritoneal carcinoma. CONCLUSION: This study demonstrates the limited value of
      diagnostic ultrasound examination as an independent modality for the detection of
      early-stage epithelial ovarian cancer in asymptomatic women who are at increased
      risk for disease.

PMID- 15846208
TI  - Obstetric outcomes in women with two prior cesarean deliveries: is vaginal birth
      after cesarean delivery a viable option?
AB  - OBJECTIVE: This study was undertaken to compare clinical outcomes in women with 1
      versus 2 prior cesarean deliveries who attempt vaginal birth after cesarean
      delivery (VBAC) and also to compare clinical outcomes of women with 2 prior
      cesarean deliveries who attempt VBAC or opt for a repeat cesarean delivery. STUDY
      DESIGN: We performed a secondary analysis of a retrospective cohort study, in
      which the medical records of more than 25,000 women with a prior cesarean
      delivery from 16 community and tertiary care hospitals were reviewed by trained
      nurse abstractors. Information on demographics, obstetric history, medical and
      social history, and the outcomes of the index pregnancy was obtained. Comparisons
      of obstetric outcomes were made between women with 1 versus 2 prior cesarean
      deliveries, and also between women with 2 prior cesarean deliveries who opt for
      VBAC attempt versus elective repeat cesarean delivery. Both bivariate and
      multivariate techniques were used for these comparisons. RESULTS: The records of
      20,175 women with one previous cesarean section and 3,970 with 2 prior cesarean
      sections were reviewed. The rate of VBAC success was similar in women with a
      single prior cesarean delivery (75.5%) compared with those with 2 prior cesarean
      deliveries (74.6%), though the odds of major morbidity were higher in those with
      2 prior cesarean deliveries (adjusted odd ratio[OR] = 1.61 95% CI 1.11-2.33).
      Among women with 2 prior cesarean deliveries, those who opt for a VBAC attempt
      had higher odds of major complications compared with those who opt for elective
      repeat cesarean delivery (adjusted OR = 2.26, 95% CI 1.17-4.37). CONCLUSION: The
      likelihood of major complications is higher with a VBAC attempt in women with 2
      prior cesarean deliveries compared with those with a single prior cesarean
      delivery. In women with 2 prior cesarean deliveries, while major complications
      are increased in those who attempt VBAC relative to elective repeat cesarean
      delivery, the absolute risk of major complications remains low.

PMID- 15846210
TI  - Benign gynecologic conditions among participants in the Breast Cancer Prevention
      Trial.
AB  - OBJECTIVE: This study was undertaken to report on the benign gynecologic
      conditions occurring among women with an intact uterus at enrollment in the
      Breast Cancer Prevention Trial of the National Surgical Adjuvant Breast and Bowel
      Project. STUDY DESIGN: The incidence rates of several benign gynecologic
      conditions were determined and risks were compared among women receiving
      tamoxifen and those receiving placebo, based on risk ratios (RRs) with 95% CIs.
      Comparisons included stratification by menopausal status, body mass index, and
      history of estrogen use. RESULTS: Compared with women taking placebo,
      premenopausal women taking tamoxifen had a greater incidence of endometrial
      polyps (RR = 1.9, 95% CI = 1.55-2.41), leiomyomas (RR = 1.3, 95% CI = 1.14-1.55),
      endometriosis (RR = 1.9, 95% CI = 1.35-2.70), ovarian cysts (RR = 1.5, 95% CI =
      1.20-1.78), and gynecologic surgical procedures, including hysterectomy (RR =
      1.6, 95% CI = 1.29-1.88). Postmenopausal women taking tamoxifen also had an
      increased incidence of endometrial polyps (RR = 2.4, 95% CI = 1.76-3.24),
      leiomyomas (RR = 1.4, 95% CI = 1.04-1.80), endometriosis (RR = 1.9, 95% CI = 1.29
      5.58), and gynecologic surgical procedures, including hysterectomy (RR = 2.2, 95%
      CI = 1.60-3.13), compared with women taking placebo. All women taking tamoxifen
      also had an increased incidence of simple endometrial hyperplasia without atypia
      (overall RR = 2.06, 95% CI = 1.64-2.60) compared with those taking placebo.
      CONCLUSIONS: Our results strongly support the estrogen agonist role of tamoxifen
      as the causative factor for the increased risk of endometrial polyps, leiomyomas,
      endometriosis, and endometrial hyperplasia among women taking this agent.

PMID- 15846213
TI  - The fibronectin receptor alpha5 integrin subunit is upregulated by cell-cell
      adhesion via a cyclic AMP-dependent mechanism: implications for human trophoblast
      migration.
AB  - Cell adhesion molecules are implicated in the mechanisms regulating trophoblast
      migration during human embryo implantation and placentation. We investigated the
      expression and subcellular organization of the fibronectin receptor alpha5
      integrin subunit during the differentiation of human trophoblasts in vitro, and
      the role of cyclic adenosine monophosphate (cAMP) in the process. Human
      trophoblasts isolated from chorionic villi expressed no alpha5 integrin, but the
      molecule was upregulated as cells aggregated in vitro. Low levels of expression
      of alpha5 integrin subunit and a diffuse cellular distribution pattern were seen
      in migrating mononuclear trophoblasts. Formation of cell aggregates was
      accompanied by increased expression of the alpha5 integrin, which translocated to
      the cytoskeleton-bound pool of proteins and clustered within focal adhesion
      plaques on the cell surface. This coincided with increased binding to
      fibronectin. In the absence of cell-cell adhesion, trophoblasts did not display
      an increase in alpha5 integrin messenger RNA or protein and there was no alpha5
      integrin in focal adhesion plaques, suggesting that cell-cell contacts
      specifically trigger the upregulation of alpha5 integrin subunit and its
      subcellular translocation. Cyclic AMP is the second messenger mediating the
      aggregation-induced increase in alpha5 integrin: cAMP increased the de novo
      synthesis of alpha5 integrin protein, particularly in mononuclear cells, whereas
      the aggregation-induced increase in alpha5 integrin was strongly inhibited by the
      antagonist Rp-cAMP in aggregating cells. Our data provide evidence that the
      alpha5 integrin mediates binding of human trophoblasts to fibronectin and is
      implicated in the regulation of trophoblast migration. This integrin's expression
      is specifically triggered by cell-cell adhesion and regulated via cAMP-mediated
      pathway(s). It is hypothesized that these mechanisms may play an important role
      in the molecular events controlling human placentation.

PMID- 15846215
TI  - Telomere length predicts embryo fragmentation after in vitro fertilization in
      women--toward a telomere theory of reproductive aging in women.
AB  - OBJECTIVE: Telomeres are DNA repeats which cap and protect chromosome ends,
      facilitate homologue pairing and chiasmata formation during early meiosis, and
      shorten with cell division and exposure to reactive oxygen to mediate aging.
      Early germ cells contain telomerase, a reverse transcriptase which adds telomeres
      to 3-prime DNA ends, but telomerase activity declines in oocytes, fixing telomere
      length earlier during development. Experimentally induced telomere shortening in
      mice disrupts meiosis, impairs chiasmata formation, halts embryonic cell cycles,
      and promotes apoptosis in embryos, a phenotype which mimics reproductive
      senescence in women. Ethical constraints limit study of human embryos to
      nondestructive assays, such as morphologic evaluation under transmission optics,
      but cytoplasmic fragmentation is a reliable marker of apoptosis. STUDY DESIGN:
      Study design consisted of observational study of effect of telomere length in
      human eggs on cytoplasmic fragmentation, and on other morphologic features of
      preimplantation embryos. To test the hypothesis that telomere shortening triggers
      apoptosis in human embryos, we evaluated telomere length as a predictor of
      cytoplasmic fragmentation in embryos from women undergoing in vitro
      fertilization. RESULTS: Telomere length negatively predicted fragmentation in day
      3 preimplantation embryos, after controlling for patient age and basal follicle
      stimulating hormone level. Telomere length did not predict other features of
      preimplantation embryo morphology. CONCLUSION: The finding that telomere length
      in human eggs predicts cytoplasmic fragmentation in embryos provides evidence
      that telomere shortening induces apoptosis in human preimplantation embryos,
      consistent with a telomere theory of reproductive senescence in women.

PMID- 15846217
TI  - Correlation of cyclooxygenase-2 (COX-2) and aromatase expression in human
      endometrial cancer: tissue microarray analysis.
AB  - OBJECTIVE: The objective of this study was to compare the prevalence of
      cyclooxygenase-2 (COX-2), aromatase, and hormone receptor immunohistochemical
      (IHC) expression to well defined clinical-pathologic prognostic factors in a
      large group of surgically staged endometrial cancer patients. STUDY DESIGN: A
      tissue microarray (TMA) was constructed from 336 separate specimens of
      endometrial cancer. IHC was performed for estrogen (ER) and progesterone (PR)
      receptor, COX-2, COX-1, and aromatase. RESULTS: The majority of tumors expressed
      COX-2 (59%) and aromatase (65%). COX-2 staining significantly correlated with
      aromatase expression ( P < .014) but did not correlate with ER and PR. COX-2
      expression was correlated with worsening histologic grade ( P < .026) and
      approached statistical significance for deep myometrial invasion ( P < .055).
      After applying multivariate analysis, no single IHC or combination of IHCs
      correlated with intrauterine poor prognostic factors or advanced stage. Only
      myometrial invasion >50% (OR 6.98, P < .001) and nonendometrioid histology (OR
      4.933, P < .001) were predictive of advanced stage after multivariate analysis.
      CONCLUSION: COX-2 and aromatase are expressed in the majority of endometrial
      cancer patients. COX-2 expression was not associated with the great majority of
      surgical-pathologic prognostic factors. COX-2 expression did significantly
      correlate with aromatase expression, suggesting that intratumoral production of
      estrogen in endometrial cancer may be an important mechanism in tumorigenesis.

PMID- 15846219
TI  - Screening candidate genes for mutations in patients with hypogonadotropic
      hypogonadism using custom genome resequencing microarrays.
AB  - OBJECTIVE: The purpose of this study was to determine the consistency of calling
      single nucleotide polymorphisms (SNPs) by custom genome resequencing microarrays
      compared with capillary DNA sequencing. STUDY DESIGN: Amplified genomic DNA from
      23 patients with hypogonadotropic hypogonadism was hybridized to microarrays
      containing 30 kilobases of sequence from 6 different candidate genes. Capillary
      DNA sequencing was performed in 10 patients. RESULTS: For 10 patients with > or
      =90% of bases called, 49 SNPs in 5 of 6 genes were identified. Of the 490 bases,
      75 were ambiguous (read as "N"), and 415 were able to be called an A, C, G, or T.
      Of 415 called, 401 (96.6%) sequences were confirmed by DNA sequencing. All
      homozygotes (285/285) were called identically, while sequence from 89.2%
      (116/130) of heterozygotes agreed by both methods. The level of agreement between
      microarray calls and capillary DNA sequencing demonstrated substantial accuracy.
      CONCLUSION: Custom genome resequencing microarrays are highly consistent with
      capillary sequencing in calling individual bases in genomic DNA from patients
      with human disease.

PMID- 15846221
TI  - RU486 inhibits expression of lysophosphatidic acid induced glycodelin.
AB  - OBJECTIVE: This study was undertaken to provide evidence for the mode of action
      of RU486 on glycodelin produced in K562 cells. To show that histiocytes may be a
      source of glycodelin in leiomyoma. STUDY DESIGN: With the use of K562, a leukemia
      cell line, the effect of lysophosphatidic acid (LPA), RU486, antioxidants, and
      ZK112,993 on glycodelin protein and gene expression was studied.
      Immunocytochemistry for glycodelin and HAM-56 (macrophage) was performed on
      leiomyoma and myometrium. RESULTS: Incubation of K562 cells with LPA,
      progesterone, ZK112,933 and RU486 significantly induced the expression of
      glycodelin protein and messenger RNA. The addition of RU486 to LPA activated
      cells markedly reduced expression of glycodelin. Addition of ZK112,993, an
      antiprogestin without antioxidant properties, to LPA activated cells did not
      reduce glycodelin. Histiocytes in leiomyoma and myometrium co-localize with
      glycodelin. CONCLUSION: RU486, partly acting as an antioxidant, markedly reduces
      LPA stimulated glycodelin production. Histiocytes in leiomyoma and myometrium
      immunostain for glycodelin and suggests a source for glycodelin in leiomyoma.

PMID- 15846224
TI  - Shortening increases spontaneous contractility in myometrium from pregnant women
      at term.
AB  - OBJECTIVE: The purpose of this study was to determine whether shortening alters
      spontaneous contractility in myometrial strips that are obtained from pregnant
      women. STUDY DESIGN: Isometric contractions were measured in myometrial strips
      that were obtained at cesarean delivery from 14 pregnant women at term. After 2
      hours of stretching, the strip lengths were decreased by 4%, 6%, or 8%.
      Spontaneous contractility was measured for 120 minutes with or without
      prostaglandin synthase inhibitor indomethacin (10 -5 mol/L), and the cumulative
      concentration response to oxytocin was determined. RESULTS: Contractility was
      increased by 29% and 34% in strips that shortened by 4% and 6%, respectively.
      Preincubation with indomethacin increased contractility by 15% in stretched
      strips and decreased contractility by 30% and 19% in 4% and 6% strips,
      respectively. Contraction frequency was increased by 26% and 53% for the strips
      that were shortened to 6% and 8%, respectively. These increases were prevented by
      indomethacin. The oxytocin responses were similar at all lengths. CONCLUSION:
      Shortening of myometrial strips from pregnant women at term increases spontaneous
      contractility by a mechanism that apparently involves prostaglandins.

PMID- 15846226
TI  - Metabolites of progesterone and the pregnane X receptor: a novel pathway
      regulating uterine contractility in pregnancy?
AB  - OBJECTIVE: The purpose of this study was to determine the role of 5beta
      dihydroprogesterone (5beta-DHP), acting through the nuclear receptor pregnane X
      receptor (PXR), in regulating uterine contractility. STUDY DESIGN: Uterine
      contractility was studied in tissues from women, rats, and mice. Messenger RNA
      was assessed using reverse transcriptase-polymerase chain reaction (RT-PCR), and
      protein was measured using enzyme assays, immunofluorescence microscopy, and
      Western analyses. RESULTS: Human and rat uterine tissues contain mRNA and protein
      for 5beta-reductase and for PXR. Acute in vitro treatment with 5beta-DHP causes
      rapid uterine relaxation that is not mediated by PXR. Chronic in vivo
      administration of 5beta-DHP to mice with intact PXR, but not in mice with
      disrupted PXR, causes an increased effect of 1400W, a specific inhibitor of
      inducible nitric oxide synthase (iNOS). This suggests that 5beta-DHP increased
      iNOS-modulated uterine tone, as occurs during pregnancy. CONCLUSION: These data
      support the hypothesis that metabolites of progesterone may act chronically
      through a PXR-mediated mechanism to regulate uterine contractility.

PMID- 15846228
TI  - The effects of progestins on bone density and bone metabolism in postmenopausal
      women: a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate the action of progestins on
      bone metabolism in early menopausal women. STUDY DESIGN: One hundred thirty-two
      menopausal women were randomized into a 2-year double-blinded, placebo-controlled
      clinical trial. There were 6 treatment groups: micronized progesterone (P 4 ) 300
      mg/day; medroxyprogesterone acetate (MPA) 10 mg/day; norethindrone (NET) 1
      mg/day; micronized estradiol (E 2 ) 1 mg/day; E 2 1 mg/day + MPA 10 mg/day; and
      placebo. All subjects received 1000 mg of calcium and 400 IU of vitamin D/day.
      Primary outcome variables were bone mineral density (BMD) changes at the spine
      and hip. Secondary variables were bone turnover markers. RESULTS: With E 2 or E 2
      +MPA treatment, BMD at L2-L4 increased by 2% to 4% over 2 years. Bone mineral
      density (BMD) at the spine followed a decreasing trend with MPA, P 4 , and
      placebo treatments. With NET treatment, BMD did not change from baseline. At the
      femoral neck site, BMD did not change significantly for any treatment group. Bone
      resorption and bone formation markers decreased with E 2 or E 2 +MPA treatment,
      and did not change appreciably with all 3 progestin-alone treatments. There were
      no vertebral or hip fractures observed during the trial. CONCLUSION: Estrogen
      remains the primary bone active agent in hormone therapy, while progestins have
      significantly less activity. The selection of the appropriate progestin in
      hormone therapy should be based on criteria other than bone activity.

PMID- 15846230
TI  - The epidemiology of threatened preterm labor: a prospective cohort study.
AB  - OBJECTIVE: The purpose of this study was to describe the occurrence, timing, and
      outcomes of hospital-based diagnoses of preterm labor. STUDY DESIGN:
      Administrative records identified hospital admissions for preterm labor among
      2534 women in an ongoing cohort study. Factors that were considered risks for
      prematurity were examined by logistic regression for an association with any
      preterm labor diagnosis, a preterm labor diagnosis <33 weeks of gestation, or >
      or =33 weeks of gestation. RESULTS: Of 234 women (9%) who experienced
      hospitalization for preterm labor, 90 women (38%) were delivered in the first
      episode. Previous preterm birth consistently was associated with a diagnosis of
      preterm labor. Reporting a sexually transmitted infection (odds ratio, 1.8; 95%
      CI, 1.1-3.0) or bacterial vaginosis (odds ratio, 2.6; 95% CI, 1.7-4.1) early in
      pregnancy was associated with hospitalization for preterm labor between 24 and 32
      weeks of gestation. CONCLUSION: The incidence of first-time hospitalization for
      preterm labor was 9%, with most episodes not resulting in preterm birth. Previous
      preterm birth was associated therefore with a preterm labor diagnosis.

PMID- 15846232
TI  - Assessment of resident surgical skills: is testing feasible?
AB  - OBJECTIVE: We have previously shown that in a single residency program objective
      structured assessment of technical skills (OSATS) is a reliable and valid method
      of assessing surgical competency. Our goal was to establish feasibility of this
      evaluation instrument when administered at multiple residency programs throughout
      the US, and assess the impact of a laboratory-based surgical curriculum on
      results. STUDY DESIGN: An OSATS exam was administered to 116 residents from 5
      residency programs. One of the residency programs had participated in a
      comprehensive surgical curriculum over a 4-year period of time. The exam
      consisted of 3 open and 3 laparoscopic tasks. Residents were graded by both a
      blinded and unblinded examiner with task-specific checklist, global rating scale,
      pass/fail assessment, and tasks were timed. All tasks were performed on life-like
      models. RESULTS: Examinations were successfully completed at all sites. Each exam
      required 90 minutes of resident time. Reliability indices calculated with
      Cronbach's alpha were .97 for overall global rating and .95 for checklists.
      Interrater reliability between blinded and unblinded examiners ranged from .71 to
      .97 for individual tasks and was .95 overall. Assessment of construct validity
      (the ability to distinguish among residency levels) found significant differences
      among the residents for both blinded and unblinded examiners for all evaluation
      outcomes except time. For the test overall, the global rating scale showed
      significant differences among all 4 residency levels. The checklist showed
      significant differences at three levels (PGY3-4 >PGY2 >PGY1). Approximate cost
      for replaceable items was 40 US dollars to 150 per resident depending on which
      tasks were chosen. Comparison of scores between residents who received a
      laboratory-based curriculum and those who did not revealed significantly higher
      scores and shorter time to complete tasks for the group who received additional
      training. CONCLUSION: Large-scale testing has confirmed that OSATS is an
      objective, reliable, and valid method to assess surgical skills, and can easily
      be administered in most residency programs. A laboratory-based surgical
      curriculum improved test results and reduced time to complete tasks.

PMID- 15846235
TI  - Is a change in the vaginal flora associated with an increased risk of preterm
      birth?
AB  - OBJECTIVE: The purpose of this study was to determine if a change in the vaginal
      flora was associated with an increased risk of preterm birth, and to determine if
      metronidazole therapy before 32 weeks increased the risk of preterm birth. STUDY
      DESIGN: We compared cultures taken at 23 to 26 weeks of gestation with cultures
      taken at delivery from women enrolled in the Vaginal Infections and Preterm Birth
      study to analyze the association of changes in the vaginal flora with preterm
      birth. RESULTS: Metronidazole therapy before 32 weeks was associated with an
      increased risk of preterm birth (OR 1.5, 95%CI 1.05-2.1) in an unadjusted model.
      A change to heavy growth of Escherichia coli or Klebsiella pneumoniae at delivery
      was found to be associated with preterm birth (OR 2.4, 95%CI 1.6-3.8). After
      controlling for race, parity, prepregnancy weight <100 pounds, smoking or
      drinking during pregnancy, Trichomonas vaginalis, bacterial vaginosis, chlamydia,
      mycoplasmas, group B streptococcus, metronidazole therapy before 32 weeks,
      vaginal pH >5.0, and an increase in E coli or K pneumoniae , only prepregnancy
      weight <100 pounds (adjusted odds ratio [AOR] 2.07, 95%CI 1.01-4.21) and
      increased E coli or K pneumoniae in the vagina at delivery (AOR 2.99, 95%CI 1.37
      6.53) were found to be significantly associated with preterm birth. CONCLUSION:
      An increase in E coli or K pneumoniae in the vagina is an independent risk factor
      for preterm birth. Changes in the vaginal flora may explain the increased risk of
      preterm birth seen with vaginal clindamycin or oral metronidazole therapy.

PMID- 15846238
TI  - Is the pneumoperitoneum the vital first step of laparoscopy?

PMID- 15846239
TI  - Usefulness of gray-scale ultrasound and complementary color Doppler ultrasound in
      the prenatal diagnosis of placenta previa accreta.

PMID- 15846240
TI  - Distance makes the bond grow stronger: inappropriate use of correlation.

PMID- 15846241
TI  - Complications of laparoscopy: an inquiry about closed versus open-entry
      technique.

PMID- 15846242
TI  - Regarding antithrombotic treatment after coronary stenting in patients on chronic
      oral anticoagulation.

PMID- 15846244
TI  - Cardiovascular disease in Latin America.

PMID- 15846245
TI  - Transseptal left heart catheterization as an alternative to retrograde left
      ventricular catheterization for patients with aortic stenosis.

PMID- 15846246
TI  - Regarding the mechanism of statin-induced myopathy.

PMID- 15846247
TI  - Aortic stenosis and angiotensin-converting enzyme inhibitors--rupture of an
      ancient paradigm?

PMID- 15846249
TI  - Letter by Spodick.

PMID- 15846250
TI  - Repeat stenting for the prevention of the early lumen loss phenomenon in patients
      with in-stent restenosis. Angiographic and intravascular ultrasound findings of a
      randomized study.
AB  - BACKGROUND: Early lumen loss (ELL) may be detected in patients undergoing
      coronary interventions for in-stent restenosis. This phenomenon may contribute to
      recurrences. This prospective, randomized study was designed to determine if
      repeat stent implantation may prevent ELL in patients with in-stent restenosis.
      METHODS: Forty patients were randomized: 20 were allocated to elective stent
      implantation and 20 to conventional balloon angioplasty. Quantitative coronary
      angiography and intravascular ultrasound (IVUS) volumetric studies were
      systematically performed (1) before the procedure, (2) immediately after
      intervention, and (3) 30 to 60 minutes later. RESULTS: Baseline characteristics
      were similar in both groups. After the delay time interval (46 +/- 8 minutes),
      quantitative coronary angiography revealed a significant reduction in minimal
      lumen diameter (2.2 +/- 0.5 mm vs 1.7 +/- 0.5 mm, P < .001) in the balloon
      angioplasty arm. Likewise, in this group, IVUS demonstrated a reduction in mean
      lumen area (7.1 +/- 2 mm2 vs 6.2 +/- 2 mm2 , P < .001) and lumen volume (144 +/-
      59 mm3 vs 126 +/- 54 mm3 , P < .001). In 4 of these patients, ELL was severe
      enough to require further intervention. In the stent arm, however, angiographic
      data and IVUS mean lumen area (7.7 +/- 3 mm2 vs 7.7 +/- 3 mm2) and lumen volume
      (161 +/- 72 mm3 vs 160 +/- 69 mm3) remained unchanged after the delay time
      interval. On multivariate analysis, stent implantation was an independent
      predictor of the absence of ELL by quantitative coronary angiography and by IVUS.
      In addition, patients with a larger ELL on IVUS had a lower event-free survival
      at 1 year (40% vs 79%, log rank P = .003). CONCLUSIONS: This randomized study
      demonstrates that (1) ELL is frequently detected after treatment of in-stent
      restenosis with balloon angioplasty, that (2) ELL influences the long-term
      clinical outcome of these patients, and that (3) repeat stent implantation
      prevents ELL.

PMID- 15846251
TI  - Efficacy and safety of a once-daily graded-release diltiazem formulation dosed at
      bedtime compared to placebo and to morning dosing in chronic stable angina
      pectoris.
AB  - BACKGROUND: The efficacy and safety of a once-daily graded-release diltiazem
      hydrochloride (GRD) formulation dosed at 10 PM in doses of 180, 360, and 420 mg
      were compared with placebo and with GRD 360 mg dosed once daily at 8 AM in
      patients (n = 311) with chronic stable angina pectoris. METHODS: This was a 3
      week multicenter, randomized, double-blind, double-dummy, parallel-group, placebo
      controlled trial. Standard Bruce protocol treadmill stress test was performed at
      baseline and end point between 6 and 8 PM (trough for evening doses) and between
      7 and 11 AM (trough for morning doses). RESULTS: All GRD evening doses showed a
      significant (P < or = .0201) increase in total duration of exercise at trough and
      a greater significant increase (P < or = .0002) at peak, compared with placebo.
      The GRD 360-mg evening dose showed the greatest increase at trough. In contrast,
      GRD 360-mg morning dose showed an increase in total duration of exercise at
      trough that was not significantly different (P = .0555) from placebo AM. GRD 360
      mg evening dose showed a 4-fold placebo-adjusted improvement compared with GRD
      360-mg morning dose between 7 and 11 AM. Significant increases (P < or = .0240)
      in time to onset of angina were obtained for all evening doses at trough and
      peak. All GRD doses were well tolerated, and incidence of adverse events for all
      GRD groups combined was less than that for placebo. CONCLUSIONS: Bedtime GRD
      significantly increases exercise tolerance in patients with angina pectoris over
      the 24-hour dosing interval. A greater 4-fold placebo-adjusted improvement
      occurred between 7 and 11 AM compared with the same morning dose, coinciding with
      the period of increased cardiovascular risk. GRD was safe and well tolerated.

PMID- 15846252
TI  - Risk reduction of cardiac events by screening of unknown asymptomatic coronary
      artery disease in subjects with type 2 diabetes mellitus at high cardiovascular
      risk: an open-label randomized pilot study.
AB  - BACKGROUND: Evaluated the efficacy of reducing the risk of cardiac events by a
      preclinical diagnosis of CAD in subjects with type 2 diabetes mellitus with 2 or
      more cardiovascular risk factors. METHODS: One hundred forty-one subjects with
      type 2 diabetes mellitus without known cardiac disease and asymptomatic, aged >45
      to <76 years, were randomized into the screening arm for CAD (71 patients) or to
      the control arm (70 patients). The screening consisted in performing an exercise
      electrocardiogram test and dipyridamole stress echocardiography; if 1 test was
      abnormal, coronary angiography is done. Screening was positive in 15 subjects
      (21.4%). At coronary angiography, which was performed in 14 of 15 patients,
      stenoses > or =50% of vessel diameter were present in 9 patients, of these 4
      underwent coronary artery bypass grafting and 4 underwent percutaneous
      transluminal coronary angioplasty. Stenoses <50% of vessel diameter were present
      in 5 patients. RESULTS: Mean follow-up was 53.5 months (range, 42-54 months).
      During this period, 1 major (myocardial infarction) and 3 minor events (angina)
      occurred in the screening arm. Eleven major and 4 minor events occurred in the
      control arm. In the screened arm, the proportion of all events was significantly
      less (P = .018) (RR .226, 95% CI 0.707-0.719, P = .012); the proportion of major
      to minor events was significantly less (P = .006) (RR .07, 95% CI 0.0087-0.565, P
      = .013). CONCLUSIONS: The preclinical diagnosis of CAD is effective in reducing
      the risk of cardiac events, especially major events, in subjects with type 2
      diabetes mellitus at high cardiovascular risk.

PMID- 15846253
TI  - Unexpected BNP levels in patients with advanced heart failure: a tale of caution
      and promise.

PMID- 15846254
TI  - Revascularization of coronary atherosclerosis in patients with diabetes mellitus-
      there is more to it than meets the image intensifier.

PMID- 15846255
TI  - Invasive versus noninvasive management of ST-elevation acute myocardial
      infarction: a review of clinical trials and observational studies.
AB  - BACKGROUND: Despite decades of research, it is still unclear whether patients
      with uncomplicated ST-segment elevation acute myocardial infarction (AMI) should
      be managed with an invasive or a noninvasive approach after successful
      thrombolysis. METHODS: We reviewed randomized trials in which patients were
      randomized to a strategy of routine cardiac catheterization after thrombolysis
      (invasive) or a strategy whereby patients received cardiac catheterization only
      if they demonstrated reversible ischemia by noninvasive testing (noninvasive). We
      also reviewed observational studies that compared outcomes for patients who were
      admitted to hospitals with and without availability of cardiac catheterization
      facilities or in different geographic regions. RESULTS: Evidence to date suggests
      that invasive approach does not result in mortality or reinfarction benefits for
      patients with uncomplicated ST-segment elevation AMI. However, all except one of
      the trials performed are dated in view of recent treatment advances, and long
      term outcomes for the recent trial have not been published. Several observational
      studies suggest that the invasive approach may improve "softer" outcomes such as
      quality of life and functional status. CONCLUSION: In conclusion, there is
      currently no evidence to support widespread use of the invasive approach among
      patients with uncomplicated ST-segment elevation AMI. However, trials with long
      term follow-up should be repeated in the current clinical context and should
      include both hard and softer outcome measures.

PMID- 15846256
TI  - Magnetic resonance imaging of coronary arteries, the ischemic cascade, and
      myocardial infarction.

PMID- 15846257
TI  - Characteristics and outcomes of patients hospitalized for heart failure in the
      United States: rationale, design, and preliminary observations from the first
      100,000 cases in the Acute Decompensated Heart Failure National Registry
      (ADHERE).
AB  - BACKGROUND: The ADHERE is designed to study characteristics, management, and
      outcomes in a broad sample of patients hospitalized with acute decompensated
      heart failure. Heart failure is a leading cause of hospitalization for adults
      older than 65 years in the United States. Most available data on these patients
      are limited by patient selection criteria and study design of clinical trials and
      single-center studies. METHODS: Participating hospitals identify patients with a
      primary or secondary discharge diagnosis of heart failure. Medical history,
      management, treatments, and health outcomes data are collected through review of
      medical records and entered into a database via secure web browser technology.
      RESULTS: As of January 2004, data on 107 362 patients have been received from 282
      participating hospitals. Of enrollees with available analyzable data (N = 105 388
      from 274 hospitals), the mean age was 72.4 (+/-14.0), and 52% were women. The
      most common comorbid conditions were hypertension (73%), coronary artery disease
      (57%), and diabetes (44%). Evidence of mild or no impairment of systolic function
      was found in 46% of patients. Inhospital mortality was 4.0% and the median
      hospital length of stay was 4.3 days. CONCLUSIONS: The ADHERE demonstrates both
      the feasibility and significant implications of gathering representative data on
      large numbers of patients hospitalized with heart failure. Initial data provided
      important insights into the clinical characteristics and patterns of care of
      these patients. Ongoing registry work will provide the framework for improved
      treatment strategies for patients hospitalized with decompensated heart failure.

PMID- 15846258
TI  - Enoxaparin versus unfractionated heparin as antithrombin therapy in patients
      receiving fibrinolysis for ST-elevation myocardial infarction. Design and
      rationale for the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial
      Infarction Treatment-Thrombolysis In Myocardial Infarction study 25 (ExTRACT-TIMI
      25).

PMID- 15846259
TI  - Design and rationale of Clopidogrel as Adjunctive Reperfusion Therapy
      Thrombolysis in Myocardial Infarction (CLARITY-TIMI) 28 trial.
AB  - BACKGROUND: Although fibrinolysis is effective in improving outcomes in ST
      elevation myocardial infarction (STEMI), failure to achieve reperfusion and/or
      reocclusion of the infarct-related artery occur in substantial proportions of
      patients during their index hospitalization and are associated with a significant
      increase in mortality. We hypothesize that the addition of clopidogrel to
      standard fibrinolytic therapy in patients with acute STEMI will improve
      reperfusion. STUDY DESIGN: CLARITY-TIMI 28 is a multicenter, international,
      randomized, double-blind, placebo-controlled trial designed to examine the
      efficacy and safety of clopidogrel when added to standard adjuvant therapy for
      fibrinolysis. The primary efficacy end point is the composite of an occluded
      infarct-related artery (defined as TIMI flow grade 0 or 1) on the predischarge
      angiogram or death or a recurrent myocardial infarction (MI) up to the start of
      coronary angiography. For subjects who do not undergo angiography, occurrence of
      death or recurrent MI by day 8 or by hospital discharge, whichever comes first,
      is used. The primary safety assessment is TIMI major bleeding. Secondary end
      points include ST resolution at 180 minutes and the clinical composite of death,
      MI, or recurrent ischemia. Substudies include analyses of biomarkers, DNA,
      continuous electrocardiogram monitoring, and initiation of treatment in the
      ambulance. CONCLUSIONS: CLARITY-TIMI 28 will help to define the role of
      clopidogrel as part of the pharmacologic reperfusion regimen for acute STEMI.

PMID- 15846260
TI  - Comparison of ezetimibe plus simvastatin versus simvastatin monotherapy on
      atherosclerosis progression in familial hypercholesterolemia. Design and
      rationale of the Ezetimibe and Simvastatin in Hypercholesterolemia Enhances
      Atherosclerosis Regression (ENHANCE) trial.
AB  - BACKGROUND: Lipid lowering through statin therapy significantly reduces the risk
      of cardiovascular events. The ENHANCE study is an international 2-year,
      randomized, double-blind, controlled trial designed to test the hypothesis that
      treatment of hypercholesterolemia by use of 2 complementary agents, ezetimibe (a
      specific cholesterol absorption inhibitor) and simvastatin (a 3-hydroxy-3
      methylglutaryl coenzyme A reductase inhibitor), will result in larger beneficial
      effects on carotid artery intima-media thickness (CA IMT) than simvastatin
      monotherapy. METHODS: The study will recruit 725 men and women with heterozygous
      familial hypercholesterolemia. After a placebo washout period, participants are
      randomized to receive daily administration of either simvastatin 80 mg and
      ezetimibe 10 mg or simvastatin 80 mg and placebo. The ENHANCE trial uses novel
      state-of-the-art single-frame digital image acquisition and rigorous quality
      assurance and control. RESULTS: The primary end point is mean change from
      baseline to 2 years in CA IMT, using composite measures from the right and left
      far wall common carotid artery, carotid bulb, and internal carotid artery.
      Secondary end points include (1) the proportion of participants who exhibit
      reductions in CA IMT, (2) the change in maximum far wall IMT, (3) the proportion
      of participants who develop new carotid artery plaques, and (4) the changes in
      carotid plus common femoral artery IMT. CONCLUSIONS: This study addresses the
      question of whether a regimen that uses drugs with different mechanisms of action
      will be of further benefit in terms of atherosclerosis reduction compared to
      statin monotherapy.

PMID- 15846262
TI  - Examining the coverage of influenza vaccination among people with cardiovascular
      disease in the United States.
AB  - BACKGROUND: People with chronic cardiovascular conditions are at increased risk
      of developing complications from relative common influenza infection. METHODS: We
      examined the coverage of influenza vaccination during the past 12 months among
      people with cardiovascular disease (CVD) using data from the National Health
      Interview Survey 2002. RESULTS: The coverage of influenza vaccination among
      people with CVD was observed to be less than optimum (32.7%) after adjusting for
      age. Among separate components studied, the coverage of influenza vaccination was
      highest among people with congestive heart failure (37.1%) and lowest among
      people with stroke (31.4%). Hypertension was the most commonly reported condition
      with influenza vaccination coverage of 32.6%. Only 22% of people with CVD aged
      <50 years reported receiving influenza vaccine in the past 12 months. For people
      in higher age groups with CVD, the coverage was 40.5% and 69.9% among people aged
      50 to 64 years and > or =65 years, respectively. CONCLUSIONS: People with CVD,
      especially those <50 years of age, should be encouraged to receive influenza
      vaccination to prevent influenza-related cardiovascular complications.

PMID- 15846263
TI  - Erythrocyte adhesiveness/aggregation: a novel biomarker for the detection of low
      grade internal inflammation in individuals with atherothrombotic risk factors and
      proven vascular disease.
AB  - BACKGROUND: We have introduced a concept of using the erythrocyte as a sensor for
      the detection of enhanced inflammation-sensitive protein concentrations. We
      presently evaluated the capability of this new biomarker to detect the presence
      of inflammation in individuals with a history of a vascular disease as opposed to
      individuals with atherothrombotic risk factors but no clinically evident vascular
      disease. METHODS: The degree of erythrocyte adhesiveness/aggregation was
      determined in the peripheral venous blood by using a simple blood test. Blood was
      drawn into a syringe containing sodium citrate and trickled onto a slide at an
      angle of 30 degrees. The slides were than scanned by a blinded technician by
      using an image analyzer to determine the area that is covered by the
      erythrocytes. RESULTS: One hundred fifty-six subjects (61 women and 95 men) of
      2586 (1238 women and 1348 men) met the criteria of a definite vascular disease
      (history of stroke, myocardial infarction, coronary artery bypass grafting, or
      peripheral vascular disease). The degree of erythrocyte aggregation was
      significantly (P = .008) higher in men, but not in women, with vascular disease
      as opposed to these without a vascular disease. The results of receiver operating
      characteristic curve analysis confirmed the diagnostic superiority of the
      erythrocyte aggregation biomarker over other commonly used markers of the acute
      phase in men. Similar results were obtained by using discriminant analysis.
      Finally, a significant correlation was found between the degree of erythrocyte
      aggregation and other markers of the acute phase suggesting its relevance for the
      detection and quantitation of low-grade inflammation in individuals with
      atherothrombosis. CONCLUSION: Erythrocyte adhesiveness/aggregation may be a
      useful biomarker to detect internal inflammation in individuals with
      atherothrombosis.

PMID- 15846264
TI  - Multimarker risk strategy for predicting 1-month and 1-year major events in non
      ST-elevation acute coronary syndromes.
AB  - BACKGROUND: The aim of this study was to define the utility of the combined
      measurement of troponin I, myoglobin, C-reactive protein, fibrinogen, and
      homocysteine to predict risk in non-ST elevation acute coronary syndromes.
      METHODS: Troponin I, myoglobin, high-sensitivity C-reactive protein, fibrinogen,
      and homocysteine were measured in 557 consecutive patients admitted to our
      institution for non-ST elevation acute coronary syndrome. The risk for major
      events (death or nonfatal myocardial infarction) at first month and at first year
      follow-up was analyzed. RESULTS: In a multivariate model adjusting for baseline
      characteristics and electrocardiographic changes, the only biomarkers related to
      major events at first month were C-reactive protein (P = .007) and myoglobin (P =
      .02), and at first year troponin I (P = .02), C-reactive protein (P = .03), and
      homocysteine (P = .04). The rate of major events depending on the number (0-5) of
      elevated biomarkers were at first month: 4.1%, 3.7%, 5.7%, 6.1%, 6.5%, and 30.8%
      (P < .0001), and at first year: 8.2%, 11.1%, 12.3%, 16.2%, 23.7%, and 50% (P <
      .0001). A simple score including the number of elevated biomarkers showed an
      adjusted risk of major events of 1.6 [1.3-1.9] at first month and of 1.4 [1.2
      1.7] at first year. CONCLUSIONS: Markers of myocardial damage, inflammation, and
      homocysteine analyzed separately provide prognostic information. The number of
      elevated biomarkers is an independent risk predictor of major events.

PMID- 15846265
TI  - Early cardiac catheterization is associated with lower mortality only among high
      risk patients with ST- and non-ST-elevation acute coronary syndromes:
      observations from the OPUS-TIMI 16 trial.
AB  - BACKGROUND: Early cardiac catheterization has been shown to improve outcomes in
      patients with non-ST-elevation acute coronary syndromes but not yet in those with
      ST-elevation myocardial infarction (STEMI). The benefit of catheterization in
      both syndromes may depend on patient risk for adverse clinical outcomes. METHODS:
      We analyzed the relation between inhospital catheterization and subsequent
      clinical outcomes based on risk profile in 8286 patients in the OPUS-TIMI 16
      Trial of patients with acute coronary syndromes. Using baseline clinical
      characteristics, patients were stratified into low-, intermediate-, and high-risk
      groups. The primary end point was 10-month mortality. The STEMI, non-STEMI
      (NSTEMI), and unstable angina subgroups were analyzed separately. RESULTS:
      Inhospital cardiac catheterization was performed in 44% of patients. Mortality
      rates at 10 months were 1.3%, 2.2%, and 11.3% in the low-, intermediate-, and
      high-risk groups, respectively. Inhospital cardiac catheterization was associated
      with a trend to lower mortality among the high-risk patients with STEMI (hazard
      ratios [HR] 0.57, 95% CI 0.33-1.01, P = .052) and NSTEMI (HR 0.65, 95% CI 0.39
      1.07, P = .088) but not in those with unstable angina (HR 0.95, 95% CI 0.63-1.43,
      P = .82). Catheterization was not associated with any significant difference in
      mortality in the low-risk or intermediate-risk group. The differences among high
      risk patients persisted after adjusting for baseline characteristics; inhospital
      catheterization was associated with significantly lower mortality in high-risk
      patients with ST and non-ST myocardial infarction (HR 0.65, 95% CI 0.45-0.95, P =
      .03). CONCLUSIONS: Inhospital cardiac catheterization is associated with lower
      mortality in high-risk patients and no difference in mortality in low-risk and
      intermediate-risk patients after STEMI and NSTEMI. These data support the
      hypothesis that high-risk patients with either STEMI or NSTEMI may benefit from
      an early invasive strategy. New prospective randomized trials are warranted,
      particularly in the STEMI population.

PMID- 15846266
TI  - Plaque erosion in the culprit lesion is prone to develop a smaller myocardial
      infarction size compared with plaque rupture.
AB  - BACKGROUND: Acute myocardial infarction (MI) stems from a disruption of the
      plaque in the coronary artery. Based on postmortem examinations, such plaque
      disruption has been classified as either a rupture or an erosion. Unfortunately,
      it has been difficult to clinically identify plaque ruptures and plaque erosions
      during the development of acute MI. To elucidate the relationships between
      clinical features and the morphological characteristics of the infarct-related
      lesions, we observed the culprit lesions in patients with acute MI by coronary
      angioscopy and intravascular ultrasound. METHODS: We examined culprit lesions in
      107 patients with acute MI using coronary angioscopy and intravascular ultrasound
      immediately before performing percutaneous coronary intervention. The lesions
      were then classified as plaque ruptures or nonruptured erosions, and their
      clinical features were compared. RESULTS: Among the lesions studied, 44 were
      classified as plaque ruptures, 28 were classified as plaque erosions, and 35 were
      unclassified. Patients with nonruptured eroded plaques had more preinfarction
      angina before the onset of MI than those with ruptured plaques (53.6% vs 22.7%, P
      = .0074). They also had less ST-segment elevation MI (71.4% vs 93.2%, P = .0185),
      lower peak creatine kinase levels (2029 +/- 1517 vs 4033 +/- 2699 IU/L, P =
      .0009), less distal embolization after percutaneous coronary intervention (3.6%
      vs 36.4%, P = .0014), and less Q-wave MI 1 month after onset (40.7% vs 88.4%, P <
      .0001). CONCLUSION: Patients with eroded plaque lesions have smaller infarctions
      than those with ruptured plaque lesions, suggesting that an eroded plaque is less
      potently thrombogenic than a ruptured plaque.

PMID- 15846267
TI  - Exercise as an alternative to oral estrogen for amelioration of endothelial
      dysfunction in postmenopausal women.
AB  - BACKGROUND: Both exercise and postmenopausal estrogen therapy augment endothelial
      function. We hypothesized that their interaction would be additive. The study
      objectives were to determine in postmenopausal women (1) the effects of an acute
      bout of exercise on brachial artery endothelium-dependent flow-mediated
      vasodilation (FMD), (2) whether these responses to exercise are augmented by
      concurrent estrogen treatment, and (3) whether these 2 interventions,
      independently or together, achieve FMD values observed in premenopausal women.
      METHODS: In postmenopausal women (n = 13; age 54 +/- 2 [mean +/- SE] years), FMD
      was quantified during supine rest and again 60 minutes after treadmill exercise
      for 45 minutes at 60% V* O2max. Subjects were studied twice: before and after 4
      weeks of oral estradiol. To obtain reference normal values, FMD was determined
      concurrently in 14 premenopausal (28 +/- 1 years) women under identical basal
      conditions. RESULTS: Flow-mediated vasodilation in postmenopausal women, markedly
      impaired when compared with premenopausal women (5.3% +/- 0.5% vs 12.1% +/- 1.5%,
      P < .01), was significantly increased by exercise (to 9.9% +/- 0.6%, P < .01). In
      contrast, after estrogen, FMD was augmented at rest (P < .01) but was not further
      enhanced after exercise (11.5% +/- 0.6% vs 9.9% +/- 0.5%, P = .3). Both
      interventions increased, independently, FMD to values in premenopausal women (P >
      .05). CONCLUSIONS: In postmenopausal women, both acute exercise and estrogen
      therapy normalize FMD. However, their effects are not additive, possibly because
      of redundancy of nitric oxide signaling pathways activated by these 2
      interventions. When considered in the context of recent trials with adverse
      cardiovascular outcomes, these results reinforce the therapeutic potential of
      exercise as an alternative nonpharmacological intervention to estrogen in
      postmenopausal women with endothelial dysfunction.

PMID- 15846268
TI  - Cost-effectiveness of iodixanol in patients at high risk of contrast-induced
      nephropathy.
AB  - BACKGROUND: Acute renal failure after contrast-induced nephropathy is a
      clinically important and costly complication after the use of iodine-based
      contrast media. We investigated the cost and cost-effectiveness of 2 contrast
      media in patients at high risk of contrast-induced nephropathy. METHODS: The
      analyses were based on a randomized, prospective, multinational clinical study
      comparing the nephrotoxic effects of an isosmolar nonionic contrast medium,
      iodixanol, with those of a low-osmolar nonionic contrast medium, iohexol.
      Resource utilization data were obtained from the study and from a retrospective
      review of patients' hospital records. Swedish, German, and French unit prices
      were applied to resources used. Between-group differences in average costs were
      analyzed using a nonparametric bootstrap method. RESULTS: Resource utilization
      data for 125 patients were analyzed. Seven contrast media-related serious adverse
      reactions, of which 6 were acute renal failures, were noted in 6 patients
      receiving iohexol. Two patients in the iodixanol group had 1 nonserious reaction
      each. The mean hospitalization cost per patient was Euros 489, Euros 573, and
      Euros 393 lower after iodixanol than after iohexol using Swedish, German, and
      French unit prices, respectively. The mean per-patient costs of treating adverse
      drug reactions were Euros 371, Euros 399, and Euros 445 lower after iodixanol
      than after iohexol, using the respective unit prices (P < or = 0.01). Iodixanol
      was cost-effective compared with iohexol, with both lower costs and better
      effects related to fewer adverse drug reactions. CONCLUSIONS: The isosmolar
      contrast medium iodixanol appears to be cost-effective when compared with a low
      osmolar contrast medium, iohexol, in diabetic patients with renal impairment
      undergoing angiography.

PMID- 15846269
TI  - Clinical factors associated with abandonment of a rate-control or a rhythm
      control strategy for the management of atrial fibrillation in the AFFIRM study.
AB  - OBJECTIVE: The objective of the current study was to determine the clinical
      factors that were associated with abandonment of a rate-control or a rhythm
      control strategy in patients with atrial fibrillation (AF). BACKGROUND: Although
      the AFFIRM Study demonstrated that outcomes are similar with a primary strategy
      of rate-control or rhythm-control for AF, there may be clinical or demographic
      factors associated with abandonment of the initial treatment strategy. Knowledge
      of these risk factors would be useful so that patients may be given appropriate
      initial therapy and, as appropriate, switched to alternative treatments earlier.
      METHODS: Patients in the AFFIRM Study were subdivided into those who were
      maintained on their initial treatment strategy versus those who abandoned initial
      treatment strategy for alternative therapies. We determined the clinical and
      demographic factors associated with change in initial treatment strategy.
      RESULTS: At 5 years the original treatment strategy was maintained in 85% of the
      patients in the rate-control arm versus 62% of those in the rhythm-control arm (P
      <.0001). Length of the qualifying episode of AF was associated with abandonment
      of both rhythm-control and rate-control strategies. Antiarrhythmic drug failure
      before randomization and a history of thyroid disease also were associated with
      abandonment of rhythm-control. Patients were more likely to maintain rate-control
      if they already had an implanted pacemaker or if they were older than 75 years,
      while an ejection fraction <30% was associated with abandonment of the rate
      control strategy. CONCLUSIONS: In patients with AF, rhythm-control strategies are
      abandoned significantly more often than rate-control strategies. Patients with
      long durations of AF on presentation or previous antiarrhythmic drug failure
      might be considered for rate-control as initial treatment.

PMID- 15846270
TI  - Impact of cardioversion strategy on functional capacity in patients with atrial
      fibrillation: the Assessment of Cardioversion Using Transesophageal
      Echocardiography (ACUTE) study.
AB  - BACKGROUND: The ACUTE Trial studied a transesophageal echocardiography (TEE)
      guided strategy compared with a conventional strategy for management of patients
      with atrial fibrillation undergoing direct current cardioversion. The primary aim
      was to determine if patient functional capacity, measured by the Duke Activity
      Status Index (DASI), would differ between treatment strategies. METHODS: The DASI
      was self-administered at study enrollment and at 8-week follow-up in 1074 (88%)
      of 1222 total patients. Clinical outcomes associated with enrollment DASI scores
      and change in follow-up DASI scores were reviewed. RESULTS: There was no
      difference between the TEE-guided (n = 544) and conventional treatment (n = 530)
      groups for mean baseline and 8-week DASI scores, adjusting for baseline; however,
      patients who improved their DASI score were more likely to be in the TEE-guided
      group (P = .03). Pooled group data showed that the higher the enrollment DASI
      score, the more it tended to be positively related to maintenance of sinus rhythm
      (P = .06) at 8 weeks. The lower the enrollment DASI score, the more it was
      predictive of death (P = .03) and bleeding (P = .01) within 8 weeks. Patients
      with congestive heart failure (CHF) at enrollment showed greater improvement in
      DASI scores at 8 weeks compared with patients without CHF (DASI Delta 45.9% vs
      31.6%, P < .001). CONCLUSIONS: There was no difference in DASI scores between
      treatment groups. However, TEE-guided treatment was a predictor of improved DASI
      at follow-up, and subgroup analysis showed that patients with CHF did show
      improvement in functional capacity with cardioversion.

PMID- 15846271
TI  - Comparative efficacy of monophasic and biphasic waveforms for transthoracic
      cardioversion of atrial fibrillation and atrial flutter.
AB  - BACKGROUND: Transthoracic cardioversion fails to restore sinus rhythm in 6% to
      33% of patients with atrial fibrillation. This study sought to determine the
      relative efficacy of biphasic waveforms compared with monophasic waveforms in the
      treatment of atrial arrhythmias. METHODS: A total of 912 patients underwent 1022
      transthoracic cardioversions between May 2000 and December 2001. A monophasic
      damped sine waveform was used in the first 304 cases, and a rectilinear biphasic
      defibrillator was used in the next 718 cases. RESULTS: Use of a biphasic waveform
      was associated with 94% success in conversion to sinus rhythm compared with 84%
      with a monophasic waveform (P < .001). The cumulative energy required to restore
      sinus rhythm was lower with biphasic shocks in both atrial fibrillation and
      atrial flutter groups (554 +/- 413 J for monophasic vs 199 +/- 216 J for biphasic
      shocks in the atrial fibrillation group, P < .001; 251 +/- 302 J vs 108 +/- 184
      J, respectively, in the atrial flutter group, P < .001). In a multivariate
      analysis, use of a biphasic shock was associated with a 3.9-fold increase in
      success of cardioversion. CONCLUSION: When used to cardiovert atrial arrhythmias,
      the rectilinear biphasic waveform was associated with higher success rates and
      lower cumulative energies than the monophasic damped sine waveform.

PMID- 15846272
TI  - Detailed bacteriologic tests to identify the origin of transvenous pacing system
      infections indicate a high prevalence of multiple organisms.
AB  - BACKGROUND: The reported incidence of pacing system-related infections (PSIs)
      varies widely, and the roles of leads and blood cultures remain poorly defined.
      METHODS: Leads and blood cultures were obtained prospectively in 224 patients
      with suspected PSIs, and the results of cultures of blood and extravascular and
      intravascular lead fragments were compared. RESULTS: In 12.3% of the patients, no
      microorganism was found on the leads. Lead cultures with > or =1 microorganism
      cultured on the extravascular and intravascular fragments of the leads were found
      in 88.5% of the positive lead cultures. Infection was caused by Staphylococcus
      epidermidis and coagulase-negative staphylococci in 66.0% and 29.5%,
      respectively. Only 33 patients had positive blood cultures according to the Duke
      criteria with the same microorganism found by lead cultures in 30 cases.
      Infection was caused by multiple organisms in 39 (25%) patients. CONCLUSION: (1)
      Regardless of the clinical presentation, the extravascular and intravascular body
      of the lead is infected, even when the infection is local. More than one
      microorganism may be implicated. (2) Bacteriologic analyses must be performed on
      several segments of each implanted lead. (3) More than 2 positive blood cultures
      are a reliable clinical criterion for the diagnosis of pacemaker lead-related
      infection, but blood cultures alone are an insensitive method to identify the
      cause of infection. (4) Up to 50% of microorganisms isolated in a single blood
      culture are also recovered in lead cultures.

PMID- 15846273
TI  - Fluvastatin reduces the impact of diabetes on long-term outcome after coronary
      intervention--a Lescol Intervention Prevention Study (LIPS) substudy.
AB  - BACKGROUND: Diabetes increases the risk of developing cardiovascular disease.
      Patients with diabetes undergoing percutaneous coronary intervention (PCI) show
      poorer outcomes compared with nondiabetic patients. The aim of this study was to
      determine the clinical benefit of long-term fluvastatin in patients with diabetes
      who had undergone a successful PCI. METHODS: This subanalysis of a prospective,
      multicenter, randomized, double-blind, placebo-controlled trial of patients who
      had undergone PCI and were treated with fluvastatin determined the impact of
      fluvastatin on the survival-free period of major adverse cardiac events (MACE)
      (defined as cardiac death, nonfatal myocardial infarction, and reintervention
      procedure [coronary artery bypass grafting, repeat PCI, PCI for a new lesion]).
      Patients with baseline total cholesterol levels of 135 to 270 mg/dL (3.5-7.0
      mmol/L) and triglyceride levels of 400 mg/dL (4.5 mmol/L) were randomized at
      discharge either to fluvastatin (n = 844) or to placebo (n = 833); follow-up was
      3 to 4 years. Among these patients, there were 202 with diabetes (120 on
      fluvastatin, 82 placebo) and 1475 without diabetes (724 on fluvastatin, 751 on
      placebo). The primary clinical outcome was survival time free of MACE and MACE
      excluding restenosis. RESULTS: The presence of diabetes increased the risk of
      MACE by almost 2-fold in placebo-treated patients (RR 1.78, 95% CI 1.20-2,64, P =
      .0045). In contrast, in diabetic patients treated with fluvastatin, the risk of
      MACE was not significantly different from that in patients without diabetes.
      Fluvastatin reduced the risk of MACE in diabetic patients by 51% (P = .0088).
      CONCLUSIONS: Diabetes is a consistent clinical predictor of cardiovascular
      complications and fluvastatin reduces the increased incidence of long-term
      adverse complications associated with the presence of diabetes.

PMID- 15846274
TI  - Randomized comparison of carbon ion-implanted stent versus bare metal stent in
      coronary artery disease: the Asian Pacific Multicenter Arthos Stent Study (PASS)
      trial.
AB  - BACKGROUND: Heavy metal ions can cause allergic and inflammatory reactions that
      might be associated with in-stent restenosis. This randomized multicenter
      clinical study was designed to determine if carbon ion-implanted stents reduce
      luminal late loss by blocking heavy metal ion diffusion into the surrounding
      tissue. METHODS: A total of 225 patients with 230 native coronary lesions were
      randomly assigned to receive either a carbon ion-implanted Arthos Inert stent
      (group 1, n = 113) or a bare metal Arthos stent (group 2, n = 117). The primary
      endpoint was in-stent luminal late loss at 6-month angiographic follow-up, and
      the secondary endpoints were the 6-month angiographic restenosis rate and the
      occurrence of the major adverse cardiac events (MACE) including death, nonfatal
      myocardial infarction, and target lesion revascularization at 12 months. RESULTS:
      The baseline characteristics were similar in the 2 groups. In-hospital events did
      not occur in any patients. Angiographic follow-up at 6 months was obtained in 184
      lesions (80%). At follow-up, the luminal late loss was similar in the 2 groups
      (0.91 +/- 0.77 mm in group 1 vs 0.88 +/- 0.80 mm in group 2, P = .79), and the
      angiographic restenosis rates were 11.0% in group 1 and 16.1% in group 2 (P =
      .31). The occurrence rates of MACE at 12 months were 9.1% in group 1 and 10.4% in
      group 2 (P = .73). CONCLUSIONS: The initial and long-term outcomes of the carbon
      ion-implanted stent were excellent. However, it did not improve long-term
      outcomes vs the bare metal stent.

PMID- 15846275
TI  - A polymorphism of the endothelial nitric oxide synthase promoter is associated
      with an increase in autonomic imbalance in patients with congestive heart
      failure.
AB  - BACKGROUND: In addition to its well-recognized role in the regulation of vascular
      tone, nitric oxide modulates sympathetic and parasympathetic nervous system
      activities. Abnormalities of both autonomic control and nitric oxide synthase
      activity are known to occur in patients with congestive heart failure. Recently,
      a polymorphism of the promoter of the endothelial nitric oxide synthase (eNOS)
      gene has been associated with a reduction of eNOS activity. This study tested the
      hypothesis that patients with congestive heart failure who are homozygous for
      this polymorphism will have a more advanced imbalance of autonomic activity.
      METHODS: Patients who have congestive heart failure were tested for the presence
      of an eNOS promoter polymorphism (thymidine to cytosine transition [T(-786)C]).
      Spectral analysis of heart rate variability was performed to quantify sympathetic
      and parasympathetic autonomic activity, which were compared between subjects
      homozygous for the polymorphism and all other subjects. RESULTS: Patients
      homozygous for the polymorphism of the eNOS promoter had a greater autonomic
      imbalance as reflected by significant differences in high- and low-frequency
      heart rate variability. These differences in autonomic function were noted in the
      absence of intergroup differences in patterns of respiratory variability,
      demographic features, and despite a higher mean ejection fraction in patients
      homozygous for the polymorphism. CONCLUSIONS: Patients with congestive heart
      failure who are homozygous for this polymorphism of the eNOS promoter were found
      to have a more advanced autonomic imbalance. This polymorphism may serve as a
      marker for patients at increased risk for sudden death and more rapid progression
      of disease.

PMID- 15846276
TI  - Screening for heart disease in diabetic subjects.
AB  - BACKGROUND: The prevalence of left ventricular hypertrophy (LVH), coronary artery
      disease, and subclinical cardiomyopathy in diabetic patients without known
      cardiac disease is unclear. We sought the frequency of these findings to
      determine whether plasma brain natriuretic peptide (BNP) could be used as an
      alternative screening tool to identify subclinical LV dysfunction. METHODS:
      Asymptomatic patients with diabetes mellitus without known cardiac disease (n =
      101) underwent clinical evaluation, measurement of BNP, exercise stress testing,
      and detailed echocardiographic assessment. After exclusion of overt dysfunction
      or ischemia, subclinical myocardial function was sought on the basis of
      myocardial systolic (Sm) and diastolic velocity (Em). Association was sought
      between subclinical dysfunction and clinical, biochemical, exercise, and
      echocardiographic variables. RESULTS; Of 101 patients, 22 had LVH and 16 had
      ischemia evidenced by exercise-induced wall motion abnormalities. Only 4 patients
      had abnormal BNP levels; BNP was significantly increased in patients with LVH.
      After exclusion of LVH and coronary artery disease, subclinical cardiomyopathy
      was identified in 24 of 66 patients. Subclinical disease could not be predicted
      by BNP. CONCLUSIONS: Even after exclusion of asymptomatic ischemia and
      hypertrophy, subclinical systolic and diastolic dysfunction occurs in a
      significant number of patients with type 2 diabetes. However, screening
      approaches, including BNP, do not appear to be sufficiently sensitive to identify
      subclinical dysfunction, which requires sophisticated echocardiographic analysis.

PMID- 15846277
TI  - Myocardial contrast echocardiography accurately reflects transmurality of
      myocardial necrosis and predicts contractile reserve after acute myocardial
      infarction.
AB  - BACKGROUND: Both myocardial contrast echocardiography (MCE) and cardiovascular
      magnetic resonance (CMR) can identify myocardial necrosis after acute myocardial
      infarction (AMI). However, transmural extent of infarction (TEI) correlates of
      myocardial perfusion by MCE after AMI are unknown. We sought to ascertain the
      ability of MCE to (1) predict TEI as defined by contrast-enhanced CMR and (2) to
      compare the relative accuracy of these techniques to predict contractile reserve
      late after AMI. METHODS: MCE and CMR were performed in 42 patients with AMI 7 to
      10 days after thrombolysis. Contractile reserve with low-dose dobutamine was
      evaluated 12 weeks after revascularization. RESULTS: Both qualitative (myocardial
      contrast intensity) and quantitative MCE [peak contrast intensity, microbubble
      velocity (beta), and myocardial blood flow] showed a significant (P < .0001)
      inverse relationship with increasing TEI. However, beta was the single best
      predictor of TEI (P = .002). Both qualitative MCE and CMR predicted contractile
      reserve similarly (area under receiver operating characteristic curve were 0.84
      and 0.80, respectively). Qualitative and quantitative MCE parameters as well as
      CMR correlated significantly with the degree of contractile reserve (P < .001).
      Multiple logistic regression analysis using clinical, electrocardiographic, MCE,
      and CMR parameters showed that both MCE (OR = 0.03, 95% CI 0.01-0.10, P < .001)
      and CMR (OR = 0.11, 95% CI 0.04-0.26, P < .001) are independent predictors of
      contractile reserve. The most discriminative quantitative parameters for
      prediction of contractile reserve were microbubble velocity (P < .001) and
      myocardial blood flow (P = .001) assessed by MCE. CONCLUSION: MCE reflects the
      transmural extent of AMI as assessed by CMR. Both techniques predict contractile
      reserve.

PMID- 15846278
TI  - B-type natriuretic peptide levels are not a surrogate marker for invasive
      hemodynamics during management of patients with severe heart failure.
AB  - BACKGROUND: We sought to assess the utility of serial BNP measurements in
      patients with severe heart failure and attempted to correlate values with
      invasively derived data. METHODS: In a retrospective study, we analyzed serial
      BNP levels in patients receiving hemodynamically guided therapy for severe heart
      failure and sought correlation with invasively derived data. RESULTS: Thirty-nine
      patients with New York Heart Association Class III-IV, with an ejection fraction
      of 35% or less, who had a pulmonary artery catheter inserted for hemodynamically
      tailored heart failure therapy, were identified and serial BNP measurements
      reviewed. BNP was estimated on admission, at 12 and 36 hours. Normally
      distributed variables are expressed as mean +/- SD and otherwise as median +/-
      interquartile range. Mean ejection fraction was 16% +/- 6%. Mean pulmonary artery
      occlusion pressures (PAOP) fell with therapy and were 25 +/- 7 mmHg, 18 +/- 7
      mmHg and 19 +/- 7 mmHg at admission, 12 hours and 36 hours respectively ( P <
      0.05). Median BNP levels fell from 1200 +/- 641 to 771 +/- 803 at 12 hours and to
      805 +/- 771 at 36 hours (P < .001). There was no correlation between BNP and any
      hemodynamically derived variable. A change in BNP was not associated with a
      change in PAOP in any individual patient. Only 42% remained alive on medical
      therapy at 30 days. CONCLUSIONS: In patients with severe heart failure, BNP
      levels do not accurately predict serial hemodynamic changes and do not obviate
      the need for pulmonary artery catheterization.

PMID- 15846285
TI  - Immunobiology of human mesenchymal stem cells and future use in hematopoietic
      stem cell transplantation.
AB  - Mesenchymal stem cells (MSCs) may be derived from adult bone marrow, fat, and
      several fetal tissues. In vitro, MSCs can be expanded and have the capacity to
      differentiate into several mesenchymal tissues, such as bone, cartilage, and fat.
      They escape the immune system in vitro, and this may make them candidates for
      cellular therapy in an allogeneic setting. They also have immunomodulatory
      effects, inhibit T-cell proliferation in mixed lymphocyte cultures, prolong skin
      allograft survival, and may decrease graft-versus-host disease (GVHD) when
      cotransplanted with hematopoietic stem cells. MSCs induce their immunosuppressive
      effect via a soluble factor. Some candidates have been suggested, and various
      mechanisms have also been suggested, although contradictory data exist; this may
      be due to differences in the cells and systems tested. A major problem has been
      that it has been difficult to identify and isolate MSCs after transplantation in
      vivo. However, MSCs seem to enhance hematopoietic engraftment in recipients of
      autologous and allogeneic grafts. Recently, they were found to reverse grade IV
      acute GVHD of the gut and liver. No tolerance was induced, however. Controlled
      studies are warranted. Thus, in allogeneic stem cell transplantation, MSCs may be
      used for hematopoiesis enhancement, as GVHD prophylaxis, and for the treatment of
      severe acute GVHD. They are also of potential use in the treatment of organ
      transplant rejection and in autoimmune inflammatory bowel disorders where
      immunomodulation and tissue repair are needed.

PMID- 15846279
TI  - Effects of metoprolol and carvedilol on cause-specific mortality and morbidity in
      patients with chronic heart failure--COMET.
AB  - BACKGROUND: Beta-blockers with different receptor bindings reduce mortality in
      patients with chronic heart failure. We compared the effects of the beta1-blocker
      metoprolol tartrate and the beta1-, beta2-, and alpha1-blocker carvedilol.
      METHODS: In a randomized double-blind design, 3029 patients with chronic
      congestive heart failure requiring diuretic therapy and with left ventricular
      dysfunction were randomized to treatment with carvedilol (n = 1511) or metoprolol
      tartrate (n = 1518) and titrated to target doses of 25 mg of carvedilol twice
      daily or 50 mg of metoprolol tartrate twice daily. The main outcome measures were
      total mortality and the combination of mortality or hospitalization for any
      cause. Secondary end points were cardiovascular death, combinations of morbidity
      and mortality, New York Heart Association class, worsening of heart failure,
      hospitalizations, and discontinuation of study therapy. RESULTS: A total of 512
      and 600 patients in the carvedilol group and metoprolol group, respectively, died
      (hazard ratio [HR] 0.83, 95% CI 0.74-0.93, P = .0017). Cardiovascular death was
      reduced by carvedilol (HR 0.80, 95% CI 0.70-0.90, P = .0004). There were fewer
      sudden deaths and deaths caused by circulatory failure or by stroke in the
      carvedilol group. There was no difference in all-cause hospitalizations or in
      worsening heart failure between treatment groups. The incidence of fatal or
      nonfatal acute myocardial infarction was significantly lower in the carvedilol
      group (HR 0.71, 95% CI 0.52-0.97, P = .03). Discontinuations of study therapy
      were similar in the 2 groups. CONCLUSION: Compared with metoprolol tartrate,
      carvedilol reduced cardiovascular mortality, sudden death, death caused by
      circulatory failure, death caused by stroke, as well as fatal and nonfatal
      myocardial infarctions.

PMID- 15846286
TI  - What role is there for antithymocyte globulin in allogeneic nonmyeloablative
      canine hematopoietic cell transplantation?
AB  - We investigated whether pretransplantation immunosuppression with canine-specific
      rabbit antithymocyte globulin (ATG), combined with a suboptimal dose of 1 Gy of
      total body irradiation (TBI), would permit engraftment of canine dog leukocyte
      antigen-identical marrow. Cumulative ATG doses of 2 to 5 mg/kg produced a T-cell
      depletion of 1 log in the peripheral blood and 50% in the lymph nodes. Serum
      levels of ATG peaked on days 4 to 6 after initiation of therapy and became
      undetectable by day 13 as a result of canine antibody responses to ATG. ATG
      prolonged allogeneic skin graft survival to 14 days (n = 5), compared with 8 days
      in control dogs (P = .0003). Five dogs were given marrow transplants after ATG
      (3.5-5 mg/kg) and 1 Gy of TBI. Posttransplantation immunosuppression consisted of
      mycophenolate mofetil and cyclosporine. All dogs showed initial engraftment, with
      maximum donor chimerism levels of 25%. However, only 1 dog achieved sustained
      engraftment, and 4 rejected their grafts. The duration of engraftment ranged from
      8 to > or = 36 weeks (median, 11 weeks), and this is comparable to that in 6
      historical controls not given ATG (range, 3-12 weeks; median, 10 weeks; P = .20).
      The total nucleated cell doses in the marrow grafts had the highest correlation
      coefficient with the duration of engraftment: 0.82 (P = .09). We concluded that
      administering ATG before an otherwise suboptimal conditioning dose of 1 Gy of TBI
      failed to secure uniform stable hematopoietic engraftment.

PMID- 15846287
TI  - Detection of microchimerism by minor histocompatibility antigen HA-1 allele
      specific nested polymerase chain reaction.
AB  - Minor histocompatibility antigens (mHags) can induce T-cell reactivities with
      important consequences for the graft-versus-leukemia effect and the development
      of graft-versus-host disease in HLA-matched stem cell transplantation settings.
      Recently, mHag-specific T cells were also demonstrated in multiparous woman and
      in solid organ transplant recipients. Microchimeric cells have been detected in
      the latter settings. To study whether microchimerism is instrumental in the
      induction and/or maintenance of mHag T cells, we developed an HA-1 allele
      specific nested polymerase chain reaction. To optimize and validate the
      reliability of this method at different levels of microchimerism, serial
      dilutions of HA-1(H) cells titrated into HA-1(R) cells were tested. We
      demonstrated that the HA-1(H) allele can be reliably and consistently detected at
      concentrations as low as 1:10(5) without losing specificity. The developed HA-1
      specific nested polymerase chain reaction is an important tool that facilitates
      the detection of HA-1 microchimerism in various clinical specimens and that
      promotes investigation of the effects of microchimerism on induction of mHag
      specific T cells in the various settings of immunization.

PMID- 15846288
TI  - Rapid and complete donor chimerism after unrelated mismatched cord blood
      transplantation in 5 children with beta-thalassemia major.
AB  - Hematopoietic stem cell transplantation is currently the only curative therapy
      for beta-thalassemia major. However, <30% of patients have unaffected HLA
      identical siblings to serve as donors. We investigated the feasibility of using
      umbilical cord blood transplants from unrelated HLA mismatched donors and a
      myeloablative preparative regimen that did not involve total body irradiation.
      Between October 2003 and November 2004, 5 children with beta-thalassemia major
      received busulfan, cyclophosphamide, and antithymocyte globulin before cord blood
      transplantation (median dose, 8.8 x 10(7) cells per kilogram of body weight) from
      unrelated donors (1 or 2 of 6 HLA antigens were mismatched) and were then
      evaluated for engraftment, adverse effects, and treatment outcome. The median
      times to neutrophil engraftment, red blood cell transfusion independence, and
      platelet engraftment were 12, 34, and 46 days after transplantation,
      respectively. All patients showed grade II or III acute graft-versus-host
      disease; none developed extensive chronic graft-versus-host disease until the
      date of last contact. All patients were alive at a median follow-up of 303 days
      after transplantation, with complete donor chimerism and transfusion
      independence. These results are encouraging and clearly show the feasibility of
      unrelated mismatched umbilical cord blood transplantation in the treatment of
      children with beta-thalassemia major.

PMID- 15846289
TI  - Long-term immune recovery of patients undergoing allogeneic stem cell
      transplantation: a comparison with their respective sibling donors.
AB  - We have addressed whether patients' immune system status after allogeneic stem
      cell transplantation, assessed more than 1 year after the procedure, recovers
      normal function as compared with that of their respective donors. An additional
      aim was to compare the status of the immune system between patients receiving
      reduced-intensity conditioning regimens and those undergoing myeloablative
      transplantations. For this purpose, we analyzed not only the different subsets of
      peripheral blood (PB) lymphocytes, but also circulating dendritic cell (DC)
      subpopulations, together with cytokine production by PB T cells, in a series of
      38 patients undergoing allogeneic stem cell transplantation. We compared these
      patients with their respective HLA-matched donors by performing a simultaneous
      patient/donor paired study. Complete bone marrow chimerism status and normal PB
      cell counts were demonstrated in all recipients. The most relevant numeric
      differences found between patients and donors were related to the distribution of
      the distinct subsets of PB DCs (CD16+ DCs were increased, whereas myeloid and
      plasmacytoid DC subsets were decreased in the patient group). This was associated
      with an increased number of B cells, an inverted CD4/CD8 T-cell ratio, and a
      decrease in CD4+/CD8+ double-positive T cells in the patient group. In addition,
      a predominance of a T-helper 1 pattern of cytokine production (interferon gamma
      and tumor necrosis factor alpha) with decreased secretion of T-helper 2
      associated cytokines (interleukin 5 and interleukin 10) was also observed at the
      single-cell level. No significant differences were found in any of the parameters
      analyzed between patients receiving reduced-intensity conditioning regimens and
      those undergoing myeloablative transplantations.

PMID- 15846290
TI  - Serious infections after unrelated donor transplantation in 136 children: impact
      of stem cell source.
AB  - How the infection risks compare after umbilical cord blood (UCB) and bone marrow
      (BM) transplantation is not known. Therefore, we compared serious infections in
      the 2 years after pediatric myeloablative unrelated donor transplantation with
      unmanipulated BM (n = 52), T cell-depleted (TCD) BM (n = 24), or UCB (n = 60) for
      the treatment of hematologic malignancy. Overall, the cumulative incidence of 1
      or more serious infections was comparable between groups (BM, 81%; TCD, 83%; UCB,
      90%; P = .12). Furthermore, by taking all serious infections into account and
      using multivariate techniques with unmanipulated BM as the reference, there were
      also no significant differences between groups (TCD relative risk [RR], 1.6; P =
      .10; UCB RR, 1.0; P = .84). Within the time periods days 0 to 42, days 43 to 100,
      and days 101 to 180, the only difference was a greater risk of viral infections
      from days 0 to 42 in TCD recipients (RR, 3.5; P = .02). Notably, after day 180,
      TCD recipients had a significantly increased infection risk (RR, 3.1; P = .03),
      whereas the risk in UCB recipients (RR, 0.5; P = .23) was comparable to that in
      BM recipients. Other factors associated with an increased infection risk in the 2
      years after transplantation were age > or = 8 years, graft failure, and severe
      acute graft-versus-host disease. These data suggest that the risk of serious
      infection after pediatric UCB transplantation is comparable to that with
      unmanipulated BM.

PMID- 15846291
TI  - Sequential expression of adhesion and costimulatory molecules in graft-versus
      host disease target organs after murine bone marrow transplantation across minor
      histocompatibility antigen barriers.
AB  - Graft-versus-host disease (GVHD) is a potentially fatal complication after
      allogeneic bone marrow transplantation. However, few data exist thus far on the
      molecular signals governing leukocyte trafficking during the disease. We
      therefore investigated the sequential pattern of distinct adhesion,
      costimulatory, and apoptosis-related molecules in GVHD organs (ileum, colon,
      skin, and liver) after transplantation across minor histocompatibility barriers
      (B10.D2 --> BALB/c, both H-2d). To distinguish changes induced by the
      conditioning regimen from effects achieved by allogeneic cell transfer, syngeneic
      transplant recipients (BALB/c --> BALB/c) and irradiated nontransplanted mice
      were added as controls. Irradiation upregulated the expression of vascular cell
      adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-l, and B7-2 in
      ileum, as well as VCAM-1 and B7-2 in colon, on day 3 in all animals. Whereas in
      syngeneic mice these effects were reversed from day 9 on, allogeneic recipients
      showed further upregulation of VCAM-1, ICAM-1, B7-1, and B7-2 in these organs on
      day 22, when GVHD became clinically evident. Infiltration of CD4+ and CD8+ donor
      T cells was noted on day 9 in skin and liver and on day 22 in ileum and colon.
      Surprisingly, the expression of several other adhesion molecules, such as ICAM-2,
      platelet-endothelial cell adhesion molecule 1, E-selectin, and mucosal addressin
      cell adhesion molecule 1, did not change. Proapoptotic and antiapoptotic markers
      were balanced in GVHD organs with the exception of spleen, in which a
      preferential expression of the proapoptotic Bax could be noted. Our results
      indicate that irradiation-induced upregulation of VCAM-1, ICAM-1, and B7-2
      provides early costimulatory signals to incoming donor T cells in the intestine,
      followed by a cascade of proinflammatory signals in other organs once the
      alloresponse is established.

PMID- 15846292
TI  - Mucositis after allogeneic hematopoietic stem cell transplantation: a cohort
      study of methotrexate- and non-methotrexate-containing graft-versus-host disease
      prophylaxis regimens.
AB  - Oral mucositis occurs in up to 75% of recipients of high-dose chemoradiotherapy
      conditioning regimens used for allogeneic hematopoietic stem cell transplantation
      (HSCT). As a result of mucositis, narcotic analgesia and total parenteral
      nutrition (TPN) are commonly required after HSCT. Methotrexate, an
      antiproliferative graft-versus-host disease (GVHD) prophylaxis agent, impairs
      mucosal regeneration and worsens and prolongs mucositis. We assessed the effect
      of substituting sirolimus for methotrexate as GVHD prophylaxis on outcomes
      associated with mucositis. Two patient cohorts undergoing allogeneic HLA-matched
      related donor peripheral blood stem cell transplantation with
      cyclophosphamide/total body irradiation conditioning were prospectively analyzed
      for mucositis severity and retrospectively reviewed for correlative outcomes.
      GVHD prophylaxis consisted of sirolimus/tacrolimus (ST) in the study group and
      tacrolimus/methotrexate (TM) in the control group. Thirty patients received ST
      and 24 patients received TM as GVHD prophylaxis between October 2000 and May
      2003. Mild, moderate, and severe mucositis was noted in 37%, 57%, and 7% of the
      ST group and 8%, 42%, and 50% of the TM group (P = .0002). Less TPN was used in
      the ST group than the TM group (17% versus 43% of posttransplantation hospital
      days; P = .02). The total number of narcotic days was lower in the ST group in
      comparison with the TM group (median, 13.5 versus 17 days; P = .08). The time to
      first hospital discharge was shorter in the ST group compared with the TM group
      (median, 18 versus 22 days; P = .07). The substitution of sirolimus for
      methotrexate as GVHD prophylaxis is associated with a reduction in mucositis
      severity. As a result, TPN and narcotic use are reduced, and hospitalization
      duration is shortened. Less toxic GVHD prophylaxis regimens without methotrexate
      may have a significant effect on patient quality of life, patient outcomes, and
      economic outcomes associated with allogeneic stem cell transplantation.

PMID- 15846293
TI  - Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem
      cells and hematopoietic stem cells in hematologic malignancy patients.
AB  - Mesenchymal stem cells (MSCs) are found in a variety of tissues, including human
      bone marrow; secrete hematopoietic cytokines; support hematopoietic progenitors
      in vitro; and possess potent immunosuppressive properties. We hypothesized that
      cotransplantation of culture-expanded MSCs and hematopoietic stem cells (HSCs)
      from HLA-identical sibling donors after myeloablative therapy could facilitate
      engraftment and lessen graft-versus-host disease (GVHD); however, the safety and
      feasibility of this approach needed to be established. In an open-label,
      multicenter trial, we coadministered culture-expanded MSCs with HLA-identical
      sibling-matched HSCs in hematologic malignancy patients. Patients received either
      bone marrow or peripheral blood stem cells as the HSC source. Patients received 1
      of 4 study-specified transplant conditioning regimens and methotrexate (days 1,
      3, and 6) and cyclosporine as GVHD prophylaxis. On day 0, patients were given
      culture-expanded MSCs intravenously (1.0-5.0 x 10(6)/kg) 4 hours before infusion
      of either bone marrow or peripheral blood stem cells. Forty-six patients (median
      age, 44.5 years; range, 19-61 years) received MSCs and HLA-matched sibling
      allografts. MSC infusions were well tolerated, without any infusion-related
      adverse events. The median times to neutrophil (absolute neutrophil count > or =
      0.500 x 10(9)/L) and platelet (platelet count > or = 20 x 10(9)/L) engraftment
      were 14.0 days (range, 11.0-26.0 days) and 20 days (range, 15.0-36.0 days),
      respectively. Grade II to IV acute GVHD was observed in 13 (28%) of 46 patients.
      Chronic GVHD was observed in 22 (61%) of 36 patients who survived at least 90
      days; it was extensive in 8 patients. Eleven patients (24%) experienced relapse
      at a median time to progression of 213.5 days (range, 14-688 days). The
      probability of patients attaining disease- or progression-free survival at 2
      years after MSC infusion was 53%. Cotransplantation of HLA-identical sibling
      culture-expanded MSCs with an HLA-identical sibling HSC transplant is feasible
      and seems to be safe, without immediate infusional or late MSC-associated
      toxicities. The optimal MSC dose and frequency of administration to prevent or
      treat GVHD during allogeneic HSC transplantation should be evaluated further in
      phase II clinical trials.

PMID- 15846294
TI  - Haploidentical stem cell transplantation with purified CD34+ cells after a
      chemotherapy-alone conditioning regimen in heavily transfused severe aplastic
      anemia.

PMID- 15846296
TI  - State-of-the-art management of locally advanced head and neck cancer.
AB  - During the past 20 years, treatments for head and neck squamous cell carcinoma
      (HNSCC) have changed dramatically owing largely to the advent of novel approaches
      such as combined modality therapy as well as improvements in surgical and
      radiotherapeutic techniques. Locally advanced disease in particular, which
      engendered very high recurrence and mortality rates, is now associated with long
      term disease-free survival in the majority of cases. This article will focus on
      locally advanced HNSCC, which frequently remains a clinical challenge, review
      state-of-the-art therapy, and introduce promising novel therapies. The field
      continues to evolve rapidly with new evidence during the past year clearly
      establishing the benefit of adjuvant chemoradiotherapy (CRT), as well as early
      evidence showing improved survival with the use of an epidermal growth factor
      receptor inhibitor in combination with radiotherapy. There are varied regimens in
      use for patients with locally advanced disease, but at the same time the
      multitude of options can plague the clinician when trying to select the most
      appropriate one. This article will attempt to put the various approaches into
      perspective and propose an evidence-based treatment algorithm.

PMID- 15846297
TI  - Lack of clinical efficacy of imatinib in metastatic melanoma.
AB  - This two-centre phase-II trial aimed at investigating the efficacy of imatinib in
      metastasised melanoma patients in correlation to the tumour expression profile of
      the imatinib targets c-kit and platelet-derived growth factor receptor (PDGF-R).
      The primary study end point was objective response according to RECIST, secondary
      end points were safety, overall and progression-free survival. In all, 18
      patients with treatment-refractory advanced melanoma received imatinib 800 mg
      day(-1). In 16 evaluable patients no objective responses could be observed. The
      median overall survival was 3.9 months, the median time to progression was 1.9
      months. Tumour biopsy specimens were obtained from 12 patients prior to imatinib
      therapy and analysed for c-kit, PDGF-Ralpha and -Rbeta expression by
      immunohistochemistry. In four cases, cell lines established from these tumour
      specimens were tested for the antiproliferative effects of imatinib and for
      functional mutations of genes encoding the imatinib target molecules. The tumour
      specimens stained positive for CD117/c-kit in nine out of 12 cases (75%), for
      PDGF-Ralpha in seven out of 12 cases (58%) and for PDGF-Rbeta in eight out of 12
      cases (67%). The melanoma cell lines showed a heterogenous expression of the
      imatinib target molecules without functional mutations in the corresponding amino
      acid sequences. In vitro imatinib treatment of the cell lines showed no
      antiproliferative effect. In conclusion, this study did not reveal an efficacy of
      imatinib in advanced metastatic melanoma, regardless of the expression pattern of
      the imatinib target molecules c-kit and PDGF-R.

PMID- 15846298
TI  - HGS-ETR1, a fully human TRAIL-receptor 1 monoclonal antibody, induces cell death
      in multiple tumour types in vitro and in vivo.
AB  - Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) induces
      apoptosis in a variety of tumour cells through activation of TRAIL-R1 and TRAIL
      R2 death signalling receptors. Here, we describe the characterisation and
      activity of HGS-ETR1, the first fully human, agonistic TRAIL-R1 mAb that is being
      developed as an antitumour therapeutic agent. HGS-ETR1 showed specific binding to
      TRAIL-R1 receptor. HGS-ETR1 reduced the viability of multiple types of tumour
      cells in vitro, and induced activation of caspase 8, Bid, caspase 9, caspase 3,
      and cleavage of PARP, indicating activation of TRAIL-R1 alone was sufficient to
      induce both extrinsic and intrinsic apoptotic pathways. Treatment of cell lines
      in vitro with HGS-ETR1 enhanced the cytotoxicity of chemotherapeutic agents
      (camptothecin, cisplatin, carboplatin, or 5-fluorouracil) even in tumour cell
      lines that were not sensitive to HGS-ETR1 alone. In vivo administration of HGS
      ETR1 resulted in rapid tumour regression or repression of tumour growth in pre
      established colon, non-small-cell lung, and renal tumours in xenograft models.
      Combination of HGS-ETR1 with chemotherapeutic agents (topotecan, 5-fluorouracil,
      and irinotecan) in three independent colon cancer xenograft models resulted in an
      enhanced antitumour efficacy compared to either agent alone. Pharmacokinetic
      studies in the mouse following intravenous injection showed that HGS-ETR1 serum
      concentrations were biphasic with a terminal half-life of 6.9-8.7 days and a
      steady-state volume of distribution of approximately 60 ml kg(-1). Clearance was
      3.6-5.7 ml(-1) day(-1) kg(-1). These data suggest that HGS-ETR1 is a specific and
      potent antitumour agent with favourable pharmacokinetic characteristics and the
      potential to provide therapeutic benefit for a broad range of human malignancies.

PMID- 15846299
TI  - Flexible, actin-based ridges colocalise with the beta1 integrin on the surface of
      melanoma cells.
AB  - Using a combination of laser-scanning confocal microscopy and atomic force
      microscopy, we have identified flexible, actin-based structures on the surface of
      cells derived from the vertical growth phase of melanoma progression. These
      flexible structures, lacking on the surface of mature melanocytes, were observed
      on the surface of all four melanoma cell lines tested. Further investigation
      revealed that the beta1 integrin colocalises with these actin-based ridges on the
      cell surface, whereas beta1 integrin distribution in melanocytes did not
      correlate with actin-based structures. Fibronectin staining on the surface of
      melanoma cells was partially codistributed with the ridges. The combination of
      structural information derived from atomic force microscopy images and
      fluorescent imaging of the distribution of labelled proteins involved in invasion
      and metastasis has allowed us to identify a common feature that may be involved
      in disease progression, at the surface of vertical growth phase melanoma cells,
      despite the known variation in genetic composition of melanoma.

PMID- 15846300
TI  - Identification of novel growth factor-responsive genes in neuroendocrine
      gastrointestinal tumour cells.
AB  - Targeting growth-regulatory pathways is a promising approach in cancer treatment.
      A prerequisite to the development of such therapies is characterisation of tumour
      growth regulation in the particular tumour cell type of interest. In order to
      gain insight into molecular mechanisms underlying proliferative responses in
      neuroendocrine (NE) gastrointestinal (GI) tumours, we investigated gene
      expression in human carcinoid BON cells after exposure to gastrin, hepatocyte
      growth factor (HGF), pituitary adenylate cyclase-activating polypeptide or
      epidermal growth factor. We particularly focused on gastrin- and HGF-induced gene
      expression, and identified 95 gastrin- and 101 HGF-responsive genes. The majority
      of these genes are known mediators of processes central in tumour biology, and a
      number of them have been associated with poor prognosis and metastasis in cancer
      patients. Furthermore, we identified 12 genes that were regulated by all four
      factors, indicating that they may be universally regulated during NE GI tumour
      cell proliferation. Our findings provide useful hypotheses for further studies
      aimed to search for new therapeutic targets as well as tumour markers in NE GI
      tumours.

PMID- 15846301
TI  - Insulin-like growth factor binding protein-6 inhibits prostate cancer cell
      proliferation: implication for anticancer effect of diethylstilbestrol in hormone
      refractory prostate cancer.
AB  - Diethylstilbestrol (DES) is a synthetic oestrogen, and its anticancer effects are
      exerted in androgen-dependent prostate cancer. The administration of DES
      decreases serum testosterone to castration levels. However, in androgen
      independent prostate cancer patients, who are already orchiectomised, the
      administration of DES improves symptoms and decreases prostate-specific antigen
      (PSA). The mechanisms responsible for these direct inhibitory effects have been
      explained as biological actions not mediated by oestrogen receptors. We assessed
      the gene expression profiles of prostate cancer cells treated with DES, and
      investigated direct inhibitory effects of DES. DES inhibited the proliferation of
      LNCaP and PC-3 cells. cDNA microarray analysis showed that expression of many
      genes was downregulated by DES. However, insulin-like growth factor binding
      protein 6 (IGFBP-6) gene expression levels were upregulated in PC-3 cells. IGFBP
      6 gene expression and protein levels significantly increased after DES treatment.
      Recombinant IGFBP-6 inhibited cell proliferation, and the inhibitory effect of
      DES was neutralised by anti-IGFBP-6 antibody. From the immunohistochemical
      analysis of IGFBP-6 using biopsy samples from androgen-independent prostate
      cancer, we found IGFBP-6 expression in androgen independent prostate cancer, and
      that DES treatment increased the IGFBP-6 staining intensity of the cancer cells
      in one sample. These findings suggested that DES induces IGFBP-6, which inhibits
      cell proliferation in an androgen-independent prostate cancer cell line, PC-3.
      IGFBP-6 therefore might be involved in the direct effects of DES in androgen
      independent prostate cancer.

PMID- 15846302
TI  - Can a rational design for metronomic chemotherapy dosing be devised?

PMID- 15846303
TI  - Two distinct Fas-activated signaling pathways revealed by an antitumor drug D609.
AB  - During the process of death receptor-mediated apoptosis, Bid is cleaved by
      activated caspase-8, and then cleaved Bid conveys apoptotic signals to the
      mitochondria by activating Bax/Bak. In the present study, we found that D609 (an
      antitumor drug with multiple activities) blocks Fas-induced apoptosis. D609 did
      not interfere with activation of caspase-8 and cleavage of Bid, whereas it
      blocked cytochrome c release from the mitochondria by inhibiting the activation
      of Bax and Bak. D609 had no protective effect against apoptosis of SKW6.4 cells,
      which are typical type I cells. Studies using permeabilized cells revealed that
      in addition to activation of caspase-8, Fas activated a distinct and D609
      sensitive signaling pathway that transmitted signal(s) sensitizing the
      mitochondria to apoptotic stimuli, and that D609 itself promoted mitochondrial
      resistance to apoptotic stimuli.

PMID- 15846304
TI  - A novel transglutaminase activator forms a complex with type 1 transglutaminase.
AB  - Type I transglutaminase is a plasma membrane-anchored intracellular protein
      protein crosslinking enzyme that is responsible for assembly of the keratinocyte
      cornified envelope during terminal keratinocyte differentiation. We recently
      described a novel protein, TIG3, that when expressed in keratinocytes causes
      increased transglutaminase activity and keratinocyte cell death. However, the
      mechanism of activation of transglutaminase by TIG3 is not known. We now extend
      our previous study and show that full-length TIG3 forms a complex with type I
      transglutaminase that is demonstrated by TIG3-transglutaminase co-precipitation.
      We also demonstrate that treating TIG3-expressing cells with monodansyl
      cadaverine, a competitive transglutaminase substrate, attenuates the TIG3
      dependent response, suggesting that transglutaminase is an important mediator of
      TIG3 action. These findings suggest that TIG3 forms a complex with
      transglutaminase resulting in transglutaminase activation and that
      transglutaminase activity is required for the TIG3-dependent biological response.

PMID- 15846306
TI  - Wanted: social entrepreneurs.

PMID- 15846305
TI  - Tobacco smoke-induced lung tumorigenesis in mutant A/J mice with alterations in K
      ras, p53, or Ink4a/Arf.
AB  - A/J mice with genetic alterations in K-ras, p53, or Ink4a/Arf were employed to
      investigate whether mice carrying these germline mutations would be susceptible
      to tobacco smoke-induced lung tumorigenesis. Transgenic mice of both genders and
      their wild-type littermates were exposed to environmental cigarette smoke for 6
      months, followed by recovery in air for 5 months. A significant increase of lung
      tumor multiplicity was observed in K-ras, p53, or Ink4a/Arf mutant mice when
      compared with wild-type mice. Furthermore, an additive effect was observed
      between the mice with a mutant p53 transgene and an Ink4A/Arf deletion during
      tobacco smoke-induced lung tumorigenesis. Sequence analysis of the K-ras gene
      indicated that the mutations had occurred at either codon 12/13 or 61 in both
      spontaneously occurring (air control) and tobacco smoke-induced lung tumors. K
      ras mutations were found in 62% of the tumors from air-control animals and 83% in
      those exposed to tobacco smoke. The mutation spectrum found in tumors from mice
      exposed to tobacco smoke is somewhat similar to that in tumors from air-control
      mice. In addition, we identified three novel mutations at codon 12: GGT (Gly) -->
      TTT (Phe), ATT (Ile), and CTT (Leu). These findings provide evidence that K-ras,
      p53, and Ink4a/Arf mutations play a role in tobacco smoke-related lung
      carcinogenesis. The similarity of the mutation spectra in the K-ras oncogene
      observed in tobacco smoke-induced tumors, as compared to spontaneous tumors,
      suggests that tobacco smoke enhances lung tumorigenesis primarily through
      promoting spontaneously occurring K-ras mutations.

PMID- 15846307
TI  - Heightened security after flu scare sparks biosafety debate.

PMID- 15846308
TI  - Conclave kindles hope for bioethical reform.

PMID- 15846309
TI  - Ecologist sues for lost tenure following transgene quarrel.

PMID- 15846311
TI  - Computer conference welcomes gobbledegook paper.

PMID- 15846310
TI  - Nobel laureate triumphs over loss of arm and returns to lab.

PMID- 15846312
TI  - Marburg workers battle to win trust of locals.

PMID- 15846313
TI  - Scientists speak out in search of fame and fortune.

PMID- 15846314
TI  - NASA boss takes the helm and launches plans for the future.

PMID- 15846316
TI  - Image manipulation: CSI: cell biology.

PMID- 15846317
TI  - Animal behaviour: when robots go wild.

PMID- 15846318
TI  - Funding shouldn't rely on competing death tolls.

PMID- 15846319
TI  - Reviewers not attached to online submission.

PMID- 15846320
TI  - Who's helping to bring science to the people?

PMID- 15846325
TI  - Striking a chord.

PMID- 15846326
TI  - Earth science: cracking the Himalaya.

PMID- 15846328
TI  - Techniques: NMR on a chip.

PMID- 15846327
TI  - Metabolism: a higher power for insulin.

PMID- 15846330
TI  - Plant biology: scented story.

PMID- 15846331
TI  - Neurobiology: sculpted by competition.

PMID- 15846332
TI  - Obituary: Hans A. Bethe (1906-2005).

PMID- 15846334
TI  - Predation: Prey plumage adaptation against falcon attack.
AB  - Several plumage types are found in feral pigeons (Columba livia), but one type
      imparts a clear survival advantage during attacks by the swiftest of all
      predators--the peregrine falcon (Falco peregrinus). Here we use quantitative
      field observations and experiments to demonstrate both the selective nature of
      the falcon's choice of prey and the effect of plumage coloration on the survival
      of feral pigeons. This plumage colour is an independently heritable trait that is
      likely to be an antipredator adaptation against high-speed attacks in open air
      space.

PMID- 15846335
TI  - Insect behaviour: arboreal ants build traps to capture prey.
AB  - To meet their need for nitrogen in the restricted foraging environment provided
      by their host plants, some arboreal ants deploy group ambush tactics in order to
      capture flying and jumping prey that might otherwise escape. Here we show that
      the ant Allomerus decemarticulatus uses hair from the host plant's stem, which it
      cuts and binds together with a purpose-grown fungal mycelium, to build a spongy
      'galleried' platform for trapping much larger insects. Ants beneath the platform
      reach through the holes and immobilize the prey, which is then stretched,
      transported and carved up by a swarm of nestmates. To our knowledge, the
      collective creation of a trap as a predatory strategy has not been described
      before in ants.

PMID- 15846336
TI  - Centennial-scale climate cooling with a sudden cold event around 8,200 years ago.
AB  - The extent of climate variability during the current interglacial period, the
      Holocene, is still debated. Temperature records derived from central Greenland
      ice cores show one significant temperature anomaly between 8,200 and 8,100 years
      ago, which is often attributed to a meltwater outflow into the North Atlantic
      Ocean and a slowdown of North Atlantic Deep Water formation--this anomaly
      provides an opportunity to study such processes with relevance to present-day
      freshening of the North Atlantic. Anomalies in climate proxy records from
      locations around the globe are often correlated with this sharp event in
      Greenland. But the anomalies in many of these records span 400 to 600 years,
      start from about 8,600 years ago and form part of a repeating pattern within the
      Holocene. More sudden climate changes around 8,200 years ago appear superimposed
      on this longer-term cooling. The compounded nature of the signals implies that
      far-field climate anomalies around 8,200 years ago cannot be used in a
      straightforward manner to assess the impact of a slowdown of North Atlantic Deep
      Water formation, and the geographical extent of the rapid cooling event 8,200
      years ago remains to be determined.

PMID- 15846337
TI  - The genome sequence of the rice blast fungus Magnaporthe grisea.
AB  - Magnaporthe grisea is the most destructive pathogen of rice worldwide and the
      principal model organism for elucidating the molecular basis of fungal disease of
      plants. Here, we report the draft sequence of the M. grisea genome. Analysis of
      the gene set provides an insight into the adaptations required by a fungus to
      cause disease. The genome encodes a large and diverse set of secreted proteins,
      including those defined by unusual carbohydrate-binding domains. This fungus also
      possesses an expanded family of G-protein-coupled receptors, several new
      virulence-associated genes and large suites of enzymes involved in secondary
      metabolism. Consistent with a role in fungal pathogenesis, the expression of
      several of these genes is upregulated during the early stages of infection
      related development. The M. grisea genome has been subject to invasion and
      proliferation of active transposable elements, reflecting the clonal nature of
      this fungus imposed by widespread rice cultivation.

PMID- 15846338
TI  - Molecular mechanisms of kinetochore capture by spindle microtubules.
AB  - For high-fidelity chromosome segregation, kinetochores must be properly captured
      by spindle microtubules, but the mechanisms underlying initial kinetochore
      capture have remained elusive. Here we visualized individual kinetochore
      microtubule interactions in Saccharomyces cerevisiae by regulating the activity
      of a centromere. Kinetochores are captured by the side of microtubules extending
      from spindle poles, and are subsequently transported poleward along them. The
      microtubule extension from spindle poles requires microtubule plus-end-tracking
      proteins and the Ran GDP/GTP exchange factor. Distinct kinetochore components are
      used for kinetochore capture by microtubules and for ensuring subsequent sister
      kinetochore bi-orientation on the spindle. Kar3, a kinesin-14 family member, is
      one of the regulators that promote transport of captured kinetochores along
      microtubules. During such transport, kinetochores ensure that they do not slide
      off their associated microtubules by facilitating the conversion of microtubule
      dynamics from shrinkage to growth at the plus ends. This conversion is promoted
      by the transport of Stu2 from the captured kinetochores to the plus ends of
      microtubules.

PMID- 15846339
TI  - No high-mass protostars in the silhouette young stellar object M17-SO1.
AB  - The birth of very massive stars is not well understood, in contrast to the
      formation process of low-mass stars like our Sun. It is not even clear that
      massive stars can form as single entities; rather, they might form through the
      mergers of smaller ones born in tight groups. The recent claim of the discovery
      of a massive protostar in M17 (a nearby giant ionized region) forming through the
      same mechanism as low-mass stars has therefore generated considerable interest.
      Here we show that this protostar has an intermediate mass of only 2.5 to 8 solar
      masses (M(o), contrary to the earlier claim of 20M(o) (ref. 8). The surrounding
      circumstellar envelope contains only 0.09M(o) and a much more extended local
      molecular cloud has 4-9M(o).

PMID- 15846340
TI  - Chronology of the early Solar System from chondrule-bearing calcium-aluminium
      rich inclusions.
AB  - Chondrules and Ca-Al-rich inclusions (CAIs) are high-temperature components of
      meteorites that formed during transient heating events in the early Solar System.
      A major unresolved issue is the relative timing of CAI and chondrule formation.
      From the presence of chondrule fragments in an igneous CAI, it was concluded that
      some chondrules formed before CAIs (ref. 5). This conclusion is contrary to the
      presence of relict CAIs inside chondrules, as well as to the higher abundance of
      26Al in CAIs; both observations indicate that CAIs pre-date chondrules by 1-3
      million years (Myr). Here we report that relict chondrule material in the Allende
      meteorite, composed of olivine and low-calcium pyroxene, occurs in the outer
      portions of two CAIs and is 16O-poor (Delta17O approximately -1 per thousand to 
      5 per thousand). Spinel and diopside in the CAI cores are 16O-rich (Delta17O up
      to -20 per thousand), whereas diopside in their outer zones, as well as melilite
      and anorthite, are 16O-depleted (Delta17O = -8 per thousand to 2 per thousand).
      Both chondrule-bearing CAIs are 26Al-poor with initial 26Al/27Al ratios of (4.7
      +/- 1.4) x 10(-6) and <1.2 x 10(-6). We conclude that these CAIs had chondrule
      material added to them during a re-melting episode approximately 2 Myr after
      formation of CAIs with the canonical 26Al/27Al ratio of 5 x 10(-5).

PMID- 15846341
TI  - Controlled multiple quantum coherences of nuclear spins in a nanometre-scale
      device.
AB  - The analytical technique of nuclear magnetic resonance (NMR) is based on coherent
      quantum mechanical superposition of nuclear spin states. Recently, NMR has
      received considerable renewed interest in the context of quantum computation and
      information processing, which require controlled coherent qubit operations.
      However, standard NMR is not suitable for the implementation of realistic
      scalable devices, which would require all-electrical control and the means to
      detect microscopic quantities of coherent nuclear spins. Here we present a self
      contained NMR semiconductor device that can control nuclear spins in a nanometre
      scale region. Our approach enables the direct detection of (otherwise invisible)
      multiple quantum coherences between levels separated by more than one quantum of
      spin angular momentum. This microscopic high sensitivity NMR technique is
      especially suitable for probing materials whose nuclei contain multiple spin
      levels, and may form the basis of a versatile multiple qubit device.

PMID- 15846342
TI  - Seasonal prediction of hurricane activity reaching the coast of the United
      States.
AB  - Much of the property damage from natural hazards in the United States is caused
      by landfalling hurricanes--strong tropical cyclones that reach the coast. For the
      southeastern Atlantic coast of the US, a statistical method for forecasting the
      occurrence of landfalling hurricanes for the season ahead has been reported, but
      the physical mechanisms linking the predictor variables to the frequency of
      hurricanes remain unclear. Here we present a statistical model that uses July
      wind anomalies between 1950 and 2003 to predict with significant and useful skill
      the wind energy of US landfalling hurricanes for the following main hurricane
      season (August to October). We have identified six regions over North America and
      over the east Pacific and North Atlantic oceans where July wind anomalies,
      averaged between heights of 925 and 400 mbar, exhibit a stationary and
      significant link to the energy of landfalling hurricanes during the subsequent
      hurricane season. The wind anomalies in these regions are indicative of
      atmospheric circulation patterns that either favour or hinder evolving hurricanes
      from reaching US shores.

PMID- 15846343
TI  - Active out-of-sequence thrust faulting in the central Nepalese Himalaya.
AB  - Recent convergence between India and Eurasia is commonly assumed to be
      accommodated mainly along a single fault--the Main Himalayan Thrust (MHT)--which
      reaches the surface in the Siwalik Hills of southern Nepal. Although this model
      is consistent with geodetic, geomorphic and microseismic data, an alternative
      model incorporating slip on more northerly surface faults has been proposed to be
      consistent with these data as well. Here we present in situ cosmogenic 10Be data
      indicating a fourfold increase in millennial timescale erosion rates occurring
      over a distance of less than 2 km in central Nepal, delineating for the first
      time an active thrust fault nearly 100 km north of the surface expression of the
      MHT. These data challenge the view that rock uplift gradients in central Nepal
      reflect only passive transport over a ramp in the MHT. Instead, when combined
      with previously reported 40Ar-39Ar data, our results indicate persistent
      exhumation above deep-seated, surface-breaking structures at the foot of the high
      Himalaya. These results suggest that strong dynamic interactions between climate,
      erosion and tectonics have maintained a locus of active deformation well to the
      north of the Himalayan deformation front.

PMID- 15846344
TI  - Geobiology of a microbial endolithic community in the Yellowstone geothermal
      environment.
AB  - The endolithic environment, the pore space of rocks, is a ubiquitous habitat for
      microorganisms on the Earth and is an important target of the search for life
      elsewhere in the Solar System. Photosynthetic, endolithic microbial communities
      commonly inhabit the outer millimetres to centimetres of all rocks exposed to the
      Earth's surface. In the most extreme terrestrial climates, such as hot and cold
      deserts, endolithic microorganisms are often the main form of life. The
      endolithic microhabitat gives protection from intense solar radiation and
      desiccation, and it provides mineral nutrients, rock moisture and growth
      surfaces. Here we describe the discovery and identification of the constituents
      of an extremely acidic (pH 1) endolithic microbial community inhabiting the pore
      space of rocks in the geothermal environment of Yellowstone National Park, USA.
      Subjected to silica mineralization, such endolithic communities constitute
      biomarkers that can become fossilized and potentially preserved in the geological
      record. Remnants of these communities could serve as biosignatures and provide
      important clues about ancient life associated with geothermal environments on the
      Earth or elsewhere in the Solar System.

PMID- 15846345
TI  - Species diversity can drive speciation.
AB  - A fundamental question in evolutionary ecology and conservation biology is: why
      do some areas contain greater species diversity than others? Island biogeographic
      theory has identified the roles of immigration and extinction in relation to area
      size and proximity to source areas, and the role of speciation is also recognized
      as an important factor. However, one as yet unexplored possibility is that
      species diversity itself might help to promote speciation, and indeed the central
      tenets of island biogeographic theory support such a prediction. Here we use data
      for plants and arthropods of the volcanic archipelagos of the Canary and Hawaiian
      Islands to address whether there is a positive relationship between species
      diversity and rate of diversification. Our index of diversification for each
      island is the proportion of species that are endemic, and we test our prediction
      that this increases with increasing species number. We show that even after
      controlling for several important physical features of islands, diversification
      is strongly related to species number.

PMID- 15846346
TI  - Sexual reproduction between partners of the same mating type in Cryptococcus
      neoformans.
AB  - Cryptococcus neoformans is a globally distributed human fungal pathogen that
      causes life-threatening meningoencephalitis in immunocompromised patients. It has
      a defined sexual cycle involving haploid cells of alpha and a mating types, yet
      the vast majority of environmental and clinical isolates are alpha (ref. 3).
      Sexual recombination is normally expected to occur between isolates of opposite
      mating type in organisms with two mating types (or sexes). How sexual
      reproductive potential can be maintained in an organism with a largely unisexual,
      nearly clonal population genetic structure is unknown. One clue, however, is that
      alpha strains undergo fruiting, a process that resembles sexual mating but is
      thought to be strictly mitotic and asexual. We report here that hallmarks of
      mating occur during fruiting, including diploidization and meiosis. Pheromone
      response pathway elements and the key meiotic regulator Dmc1 are required for
      efficient fruiting. Furthermore, fusion and meiosis can occur between non
      isogenic alpha strains, enabling genetic exchange. These studies reveal how
      sexual reproduction can occur between partners of the same mating type. These
      findings have implications for the evolution of microbial pathogens, as well as
      for parthenogenesis, cell fusion events and transitions between self-fertilizing
      and outcrossing modes of reproduction observed in both fungi and other kingdoms.

PMID- 15846347
TI  - Regulation of axon growth in vivo by activity-based competition.
AB  - The formation of functional neural networks requires precise regulation of the
      growth and branching of the terminal arbors of axons, processes known to be
      influenced by early network electrical activity. Here we show that a rule of
      activity-based competition between neighbouring axons appears to govern the
      growth and branching of retinal ganglion cell (RGC) axon arbors in the developing
      optic tectum of zebrafish. Mosaic expression of an exogenous potassium channel or
      a dominant-negative SNARE protein was used to suppress electrical or
      neurosecretory activity in subsets of RGC axons. Imaging in vivo showed that
      these forms of activity suppression strongly inhibit both net growth and the
      formation of new branches by individually transfected RGC axon arbors. The
      inhibition is relieved when the activity of nearby 'competing' RGC axons is also
      suppressed. These results therefore identify a new form of activity-based
      competition rule that might be a key regulator of axon growth and branch
      initiation.

PMID- 15846348
TI  - Hypothalamic K(ATP) channels control hepatic glucose production.
AB  - Obesity is the driving force behind the worldwide increase in the prevalence of
      type 2 diabetes mellitus. Hyperglycaemia is a hallmark of diabetes and is largely
      due to increased hepatic gluconeogenesis. The medial hypothalamus is a major
      integrator of nutritional and hormonal signals, which play pivotal roles not only
      in the regulation of energy balance but also in the modulation of liver glucose
      output. Bidirectional changes in hypothalamic insulin signalling therefore result
      in parallel changes in both energy balance and glucose metabolism. Here we show
      that activation of ATP-sensitive potassium (K(ATP)) channels in the mediobasal
      hypothalamus is sufficient to lower blood glucose levels through inhibition of
      hepatic gluconeogenesis. Finally, the infusion of a K(ATP) blocker within the
      mediobasal hypothalamus, or the surgical resection of the hepatic branch of the
      vagus nerve, negates the effects of central insulin and halves the effects of
      systemic insulin on hepatic glucose production. Consistent with these results,
      mice lacking the SUR1 subunit of the K(ATP) channel are resistant to the
      inhibitory action of insulin on gluconeogenesis. These findings suggest that
      activation of hypothalamic K(ATP) channels normally restrains hepatic
      gluconeogenesis, and that any alteration within this central nervous system/liver
      circuit can contribute to diabetic hyperglycaemia.

PMID- 15846349
TI  - Sox2 is required for sensory organ development in the mammalian inner ear.
AB  - Sensory hair cells and their associated non-sensory supporting cells in the inner
      ear are fundamental for hearing and balance. They arise from a common progenitor,
      but little is known about the molecular events specifying this cell lineage. We
      recently identified two allelic mouse mutants, light coat and circling (Lcc) and
      yellow submarine (Ysb), that show hearing and balance impairment. Lcc/Lcc mice
      are completely deaf, whereas Ysb/Ysb mice are severely hearing impaired. We
      report here that inner ears of Lcc/Lcc mice fail to establish a prosensory domain
      and neither hair cells nor supporting cells differentiate, resulting in a severe
      inner ear malformation, whereas the sensory epithelium of Ysb/Ysb mice shows
      abnormal development with disorganized and fewer hair cells. These phenotypes are
      due to the absence (in Lcc mutants) or reduced expression (in Ysb mutants) of the
      transcription factor SOX2, specifically within the developing inner ear. SOX2
      continues to be expressed in the inner ears of mice lacking Math1 (also known as
      Atoh1 and HATH1), a gene essential for hair cell differentiation, whereas Math1
      expression is absent in Lcc mutants, suggesting that Sox2 acts upstream of Math1.

PMID- 15846350
TI  - Visualizing the mechanical activation of Src.
AB  - The mechanical environment crucially influences many cell functions. However, it
      remains largely mysterious how mechanical stimuli are transmitted into
      biochemical signals. Src is known to regulate the integrin-cytoskeleton
      interaction, which is essential for the transduction of mechanical stimuli. Using
      fluorescent resonance energy transfer (FRET), here we develop a genetically
      encoded Src reporter that enables the imaging and quantification of spatio
      temporal activation of Src in live cells. We introduced a local mechanical
      stimulation to human umbilical vein endothelial cells (HUVECs) by applying laser
      tweezer traction on fibronectin-coated beads adhering to the cells. Using the Src
      reporter, we observed a rapid distal Src activation and a slower directional wave
      propagation of Src activation along the plasma membrane. This wave propagated
      away from the stimulation site with a speed (mean +/- s.e.m.) of 18.1 +/- 1.7 nm
      s(-1). This force-induced directional and long-range activation of Src was
      abolished by the disruption of actin filaments or microtubules. Our reporter has
      thus made it possible to monitor mechanotransduction in live cells with spatio
      temporal characterization. We find that the transmission of mechanically induced
      Src activation is a dynamic process that directs signals via the cytoskeleton to
      spatial destinations.

PMID- 15846351
TI  - Breaking the bottleneck.

PMID- 15846352
TI  - Counting the cost.

PMID- 15846354
TI  - Scientists and societies. Postdoc problems--postdoc solutions.

PMID- 15846357
TI  - Of fish and chips.

PMID- 15846358
TI  - Watching and weighting--chaperone complexes in action.

PMID- 15846359
TI  - Neural stem cells and neurospheres--re-evaluating the relationship.
AB  - For most of the past century, the prospect of replacing lost or damaged cells in
      the central nervous system (CNS) was hampered by the opinion that the adult
      mammalian CNS was incapable of generating new nerve cells. This belief, like most
      dogmas, was essentially founded on a lack of experimental evidence to the
      contrary. The overturning of this 'no new neuron' hypothesis began midway through
      the twentieth century with a series of reports documenting neurogenesis in the
      postnatal and adult brain, continued with the isolation and in vitro culture of
      neurogenic cells from the adult mammalian brain, and culminated in the discovery
      of a population of multipotent, self-renewing cells in the adult CNS (that is,
      bona fide neural stem cells). Although a variety of techniques were initially
      used, the neurosphere assay (NSA) rapidly emerged as the assay of choice and has
      since become a valuable tool for isolating, and understanding the biology of,
      embryonic and adult CNS stem cells. Like all technologies, it is not without its
      limitations. In this article we will highlight several shortcomings of the assay
      related to its application and interpretation that we believe have led to a
      significant body of research whose conclusions may well be misleading.

PMID- 15846360
TI  - Independence and reproducibility across microarray platforms.
AB  - Microarrays have been widely used for the analysis of gene expression, but the
      issue of reproducibility across platforms has yet to be fully resolved. To
      address this apparent problem, we compared gene expression between two microarray
      platforms: the short oligonucleotide Affymetrix Mouse Genome 430 2.0 GeneChip and
      a spotted cDNA array using a mouse model of angiotensin II-induced hypertension.
      RNA extracted from treated mice was analyzed using Affymetrix and cDNA platforms
      and then by quantitative RT-PCR (qRT-PCR) for validation of specific genes. For
      the 11,710 genes present on both arrays, we assessed the relative impact of
      experimental treatment and platform on measured expression and found that
      biological treatment had a far greater impact on measured expression than did
      platform for more than 90% of genes, a result validated by qRT-PCR. In the small
      number of cases in which platforms yielded discrepant results, qRT-PCR generally
      did not confirm either set of data, suggesting that sequence-specific effects may
      make expression predictions difficult to make using any technique.

PMID- 15846361
TI  - Multiple-laboratory comparison of microarray platforms.
AB  - Microarray technology is a powerful tool for measuring RNA expression for
      thousands of genes at once. Various studies have been published comparing
      competing platforms with mixed results: some find agreement, others do not. As
      the number of researchers starting to use microarrays and the number of cross
      platform meta-analysis studies rapidly increases, appropriate platform
      assessments become more important. Here we present results from a comparison
      study that offers important improvements over those previously described in the
      literature. In particular, we noticed that none of the previously published
      papers consider differences between labs. For this study, a consortium of ten
      laboratories from the Washington, DC-Baltimore, USA, area was formed to compare
      data obtained from three widely used platforms using identical RNA samples. We
      used appropriate statistical analysis to demonstrate that there are relatively
      large differences in data obtained in labs using the same platform, but that the
      results from the best-performing labs agree rather well.

PMID- 15846362
TI  - Standardizing global gene expression analysis between laboratories and across
      platforms.
AB  - To facilitate collaborative research efforts between multi-investigator teams
      using DNA microarrays, we identified sources of error and data variability
      between laboratories and across microarray platforms, and methods to accommodate
      this variability. RNA expression data were generated in seven laboratories, which
      compared two standard RNA samples using 12 microarray platforms. At least two
      standard microarray types (one spotted, one commercial) were used by all
      laboratories. Reproducibility for most platforms within any laboratory was
      typically good, but reproducibility between platforms and across laboratories was
      generally poor. Reproducibility between laboratories increased markedly when
      standardized protocols were implemented for RNA labeling, hybridization,
      microarray processing, data acquisition and data normalization. Reproducibility
      was highest when analysis was based on biological themes defined by enriched Gene
      Ontology (GO) categories. These findings indicate that microarray results can be
      comparable across multiple laboratories, especially when a common platform and
      set of procedures are used.

PMID- 15846363
TI  - Activity probe for in vivo profiling of the specificity of proteasome inhibitor
      bortezomib.
AB  - Proteasome inhibitors, such as the dipeptide boronic acid bortezomib, are
      emerging as important tools in the treatment of the fatal hematologic malignancy
      multiple myeloma. Despite the recent US Food and Drug Administration approval of
      bortezomib (PS341, Velcade) for the treatment of refractory multiple myeloma,
      many of the basic pharmacologic parameters of bortezomib and its mode of action
      on myeloma cells remain to be determined. We describe the synthesis and use of a
      cell-permeant active site-directed probe, which allows profiling of proteasomal
      activities in living cells. When we compared proteasome activity patterns in
      cultured cells and crude cell extracts with this probe, we observed substantial
      differences, stressing the importance for bioassays compatible with live cells to
      ensure accuracy of such measurements. Using this probe, we investigated the in
      vivo subunit specificities of bortezomib and another inhibitor, MG132.

PMID- 15846364
TI  - Quantitative analysis of gene expression in living adult neural stem cells by
      gene trapping.
AB  - The potential of neural stem cells (NSCs) for the treatment of neurodegenerative
      diseases makes the identification and characterization of genes involved in
      neural stem cell responses therapeutically important. Although technologies exist
      for measuring gene expression in cells, they often provide only a representative
      expression profile specific to a stimulus and time. We developed a complementary
      technology based on a retroviral-vector gene-trap approach that uses beta
      lactamase-induced disruption of fluorescence resonance energy transfer in the
      fluorophore CCF-2/AM. A library of 'tagged' adult rat NSCs was generated by
      transduction with gene-trap virus produced from a single-integrant packaging cell
      line that allowed us to quantitatively analyze dynamic gene expression changes in
      real time in living NSCs. Using this library we identified previously unknown
      genes regulated by oxidative stress, indomethacin and factors that induce
      differentiation, and show that one of the trapped genes, Sox6, is sufficient to
      induce astrocytic differentiation when overexpressed.

PMID- 15846365
TI  - Monitoring macromolecular complexes involved in the chaperonin-assisted protein
      folding cycle by mass spectrometry.
AB  - We have used native mass spectrometry to analyze macromolecular complexes
      involved in the chaperonin-assisted refolding of gp23, the major capsid protein
      of bacteriophage T4. Adapting the instrumental methods allowed us to monitor all
      intermediate complexes involved in the chaperonin folding cycle. We found that
      GroEL can bind up to two unfolded gp23 substrate molecules. Notably, when GroEL
      is in complex with the cochaperonin gp31, it binds exclusively one gp23. We also
      demonstrated that the folding and assembly of gp23 into 336-kDa hexamers by GroEL
      gp31 can be monitored directly by electrospray ionization mass spectrometry (ESI
      MS). These data reinforce the great potential of ESI-MS as a technique to
      investigate structure-function relationships of protein assemblies in general and
      the chaperonin-protein folding machinery in particular. A major advantage of
      native mass spectrometry is that, given sufficient resolution, it allows the
      analysis at the picomole level of sensitivity of heterogeneous protein complexes
      with molecular masses up to several million daltons.

PMID- 15846368
TI  - Preclinical evaluation of autologous dendritic cells transfected with mRNA or
      loaded with apoptotic cells for immunotherapy of high-risk neuroblastoma.
AB  - Children with high-risk neuroblastoma (NB) have a poor clinical outcome. The
      purpose of the present study was to evaluate different strategies for
      immunotherapy of high-risk NB based on vaccination with antigen-loaded dendritic
      cells (DCs). DCs are professional antigen-presenting cells with the ability to
      induce antitumor T-cell responses. We have compared DCs either loaded with
      apoptotic tumor cells or transfected with mRNA from the NB cell line HTB11 SK-N
      SH, for their capacity to induce T-cell responses in vitro. Monocyte-derived DCs
      from healthy donors were loaded with tumor-derived antigens in the form of
      apoptotic cells or mRNA, matured and used to prime autologous T cells in vitro.
      After 1 week, T-cell responses against antigen-loaded DCs were measured by
      ELISPOT assay. DCs loaded with apoptotic NB cells or transfected with NB-cell
      mRNA were both able to efficiently activate autologous T cells. Both T cells of
      the CD8+ and CD4+ subset were activated. T cells activated by NB mRNA transfected
      DCs extensively crossreacted with DCs loaded with apoptotic NB cells and vice
      versa. The results indicate that loading of DCs with apoptotic NB cells or
      transfection with tumor mRNA represent promising strategies for development of
      individualized cancer vaccines/cancer gene therapy in treatment of NB.

PMID- 15846369
TI  - Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell
      proliferation.
AB  - APRIL, a proliferation-inducing ligand, is a member of the tumor necrosis factor
      (TNF) family that is expressed by various types of tumors and influences their
      growth in vitro and in vivo. Two receptors, transmembrane activator and
      cyclophilin ligand interactor (TACI) and B-cell maturation antigen (BCMA), bind
      APRIL, but neither is essential for the tumor-promoting effects, suggesting that
      a third receptor exists. Here, we report that APRIL specifically binds to heparan
      sulfate proteoglycans (HSPG) on the surface of tumor cells. This binding is
      mediated by the heparin sulfate side chains and can be inhibited by heparin.
      Importantly, BCMA and HSPG do not compete, but can bind APRIL simultaneously,
      suggesting that different regions in APRIL are critical for either interaction.
      In agreement, mutation of three lysines in a putative heparin sulfate-binding
      motif, which is not part of the TNF fold, destroys interaction with HSPG, while
      binding to BCMA is unaffected. Finally, whereas interaction of APRIL with HSPG
      does not influence APRIL-induced proliferation of T cells, it is crucial for its
      tumor growth-promoting activities. We therefore conclude that either HSPG serve
      as a receptor for APRIL or that HSPG binding allows APRIL to interact with a
      receptor that promotes tumor growth.

PMID- 15846370
TI  - Induction of annexin-1 during TRAIL-induced apoptosis in thyroid carcinoma cells.

PMID- 15846371
TI  - Neuroprotection by the caspase-1 inhibitor Ac-YVAD-(acyloxy)mk in experimental
      neuroAIDS is independent from IL-1beta generation.

PMID- 15846372
TI  - The dsRNA-dependent protein kinase, PKR and cell death.

PMID- 15846373
TI  - tBid induces alterations of mitochondrial fatty acid oxidation flux by malonyl
      CoA-independent inhibition of carnitine palmitoyltransferase-1.
AB  - Recent studies suggest a close relationship between cell metabolism and
      apoptosis. We have evaluated changes in lipid metabolism on permeabilized
      hepatocytes treated with truncated Bid (tBid) in the presence of caspase
      inhibitors and exogenous cytochrome c. The measurement of beta-oxidation flux by
      labeled palmitate demonstrates that tBid inhibits beta-oxidation, thereby
      resulting in the accumulation of palmitoyl-coenzyme A (CoA) and depletion of
      acetyl-carnitine and acylcarnitines, which is pathognomonic for inhibition of
      carnitine palmitoyltransferase-1 (CPT-1). We also show that tBid decreases CPT-1
      activity by a mechanism independent of both malonyl-CoA, the key inhibitory
      molecule of CPT-1, and Bak and/or Bax, but dependent on cardiolipin decrease.
      Overexpression of Bcl-2, which is able to interact with CPT-1, counteracts the
      effects exerted by tBid on beta-oxidation. The unexpected role of tBid in the
      regulation of lipid beta-oxidation suggests a model in which tBid-induced
      metabolic decline leads to the accumulation of toxic lipid metabolites such as
      palmitoyl-CoA, which might become participants in the apoptotic pathway.

PMID- 15846374
TI  - Fatty acids liberated from low-density lipoprotein trigger endothelial apoptosis
      via mitogen-activated protein kinases.
AB  - Enzymatic modification of low-density lipoprotein (LDL) as it probably occurs in
      the arterial intima drastically increases its cytotoxicity, which could be
      relevant for the progression of atherosclerotic lesions. LDL was treated with a
      protease and cholesterylesterase to generate a derivative similar to lesional
      LDL, with a high content of free cholesterol and fatty acids. Exposure of
      endothelial cells to the enzymatically modified lipoprotein (E-LDL), but not to
      native or oxidized LDL, resulted in programmed cell death. Apoptosis was
      triggered by apoptosis signal-regulating kinase 1 dependent phosphorylation of
      p38. Depletion and reconstitution experiments identified free fatty acids (FFA)
      as the triggers of this pathway. Levels of FFA in native LDL are low and the
      lipoprotein is therefore not cytotoxic; enzymatic cleavage of cholesterylesters
      liberates FFA that can rapidly trigger an apoptosis signaling cascade in
      neighboring cells. Blockade of this pathway can rescue cells from death.

PMID- 15846375
TI  - Cellular prion protein inhibits proapoptotic Bax conformational change in human
      neurons and in breast carcinoma MCF-7 cells.
AB  - Prion protein (PrP) prevents Bcl-2-associated protein X (Bax)-mediated cell
      death, but the step at which PrP inhibits is not known. We first show that PrP is
      very specific for Bax and cannot prevent Bak (Bcl-2 antagonist killer 1)-, tBid-,
      staurosporine- or thapsigargin-mediated cell death. As Bax activation involves
      Bax conformational change, mitochondrial translocation, cytochrome c release and
      caspase activation, we investigated which of these events was inhibited by PrP.
      PrP inhibits Bax conformational change, cytochrome c release and cell death in
      human primary neurons and MCF-7 cells. Serum deprivation-induced Bax
      conformational change is more rapid in PrP-null cells. PrP does not prevent
      active caspase-mediated cell death. PrP does not colocalize with Bax in normal or
      apoptotic primary neurons and cannot prevent Bax-mediated cytochrome c release in
      a mitochondrial cell-free system. We conclude that PrP protects against Bax
      mediated cell death by preventing the Bax proapoptotic conformational change that
      occurs initially in Bax activation.

PMID- 15846376
TI  - Proapoptotic regimes for HTLV-I-transformed cells: targeting Tax and the NF
      kappaB pathway.

PMID- 15846377
TI  - Multiple death pathways in retina-derived 661W cells following growth factor
      deprivation: crosstalk between caspases and calpains.
AB  - During development of the mammalian retina, neurons that do not succeed in
      establishing functional synaptic connections are eliminated by apoptosis,
      allowing the formation of a finely tuned network. Growth factors play a crucial
      role in controlling the balance between apoptosis and survival signals not only
      at developmental stages but also in long-term preservation of retinal functions.
      In the present work, we explore the apoptotic mechanisms triggered by growth
      factor deprivation of retina-derived 661W cells. Under serum starvation
      conditions, these cone photoreceptors underwent cell death with participation of
      caspase-9, -3 and -12. Interestingly, inhibition of caspases did not prevent
      apoptosis but only resulted in a temporary delay. We show m-calpain activation in
      parallel with caspases, indicating that more than one execution pathway is
      available to cone photoreceptors. Moreover, crosstalk of the caspase and calpain
      pathways was detected, suggesting a loop that may act to amplify the apoptotic
      cascade.

PMID- 15846378
TI  - BCR/ABL, mRNA translation and apoptosis.

PMID- 15846379
TI  - Cell death mechanisms in HIV-associated dementia: the involvement of syncytia.

PMID- 15846380
TI  - Central serous chorioretinopathy associated with testosterone therapy.

PMID- 15846381
TI  - Corneal astigmatism in Graves' ophthalmopathy.
AB  - PURPOSE: To describe corneal astigmatism in patients under the age of 55 years
      with Graves' ophthalmopathy and to compare it to a control group. METHODS:
      Retrospective, nonrandomized comparative observational case series. A total of
      109 patients with inactive Graves' ophthalmopathy and 109 age- and gender-matched
      control individuals without Graves' ophthalmopathy were examined with manual
      corneal keratometry. In the Graves' patients, 52% had a CT scan available for
      review, and 41% underwent orbital, strabismus, and/or eyelid surgery with a
      follow-up of keratometry over a mean period of 1.7 years after surgery. RESULTS:
      For the dioptres, there was a statistically significant difference between the
      Graves' and the control eyes at 3-3.25 dioptres in both eyes (t-test, right eyes,
      P=0.042; left eyes, P=0.041). For the meridians, the astigmatism was found to be
      greater at the meridians 95-100 degrees (t-test, P=0.044) and 105 degrees -110
      degrees (t-test, P=0.017) in the right eyes only. In 10 (9%) Graves' patients,
      the astigmatism had caused newly acquired reduced visual acuity. Greater
      astigmatism in dioptres did not correlate with specific CT scan findings (chi(2)
      test, df=2, P=0.187). Following orbital, strabismus, and eyelid surgery, the
      dioptres and meridians of the astigmatism did not change in 56 (68%) and 66 (81%)
      eyes, respectively. CONCLUSIONS: Graves' ophthalmopathy may be associated with
      greater with-the-rule corneal astigmatism, which, overall, is not influenced by
      orbital, strabismus, or eyelid surgery. The astigmatism may possibly be caused by
      soft-tissue fibrosis in the superolateral orbital region.

PMID- 15846382
TI  - Intravitreal triamcinolone staining observation of residual undetached cortical
      vitreous after posterior vitreous detachment.
AB  - AIMS: To study the pattern of residual undetached cortical vitreous (RCV) after
      posterior vitreous detachment (PVD) in eyes with rhegmatogenous retinal
      detachment (RRD) and to examine the relationship between RCV and the development
      of epiretinal membrane (ERM). METHODS: A prospective study was conducted in 33
      consecutive patients with clinically evident PVD who underwent pars plana
      vitrectomy for RRD. During vitrectomy, triamcinolone acetonide (0.2 cm(3), 10
      mg/cm(3)) was applied to stain the RCV. The pattern of the staining were
      recorded. The formation of postoperative ERM was correlated with the staining
      pattern of RCV. Each case was followed for at least 6 months. RESULTS: In all, 23
      of the 33 patients had RCV of variable size, with a single stain patch observed
      in 13 patients and multiple patches in seven patients. Large circumferential
      areas of staining at the mid-periphery were noted in three patients. A total of
      10 cases had staining over the fovea and five patients had staining over the
      disc. ERM developed in seven patients during follow-up. None corresponded to RCV.
      CONCLUSION: RCV is common in eyes with PVD and RRD. The macula and disc area are
      the most frequent locations for these vitreous islands. The relationship between
      RCV and ERM remains to be investigated.

PMID- 15846383
TI  - Familial Arnold-Chiari Type I malformation.

PMID- 15846384
TI  - Modified laser DCR for paediatric nasolacrimal duct obstruction.
AB  - AIMS: To evaluate the efficacy, safety, and long-term outcome of modified laser
      dacryocystorhinostomy (DCR) for primary nasolacrimal duct obstruction,
      unresponsive to probing. METHODS: Retrospective, noncomparative case-note review
      of all paediatric cases operated between September 2000 and November 2003.
      PROCEDURE: A fibre optic light, inserted through the canaliculi into the lacrimal
      sac was visualized endonasally. Nasal mucosa was incised using a keratome and a
      bony ostium was created with the Holmium : YAG laser. Bicanalicular silicone
      tubes were inserted. RESULTS: Five children with a mean follow-up of 25.6 months
      (range 21-48 months) and a mean age of 7 years were reviewed. Silicone tubes were
      used in four patients and were removed at a mean 6.5 months (range 3-9 months).
      One patient developed a mucocele 6 months after the procedure requiring excision
      of the membrane covering the ostium. There were no other immediate or late
      postoperative complications. Complete cure of symptoms was achieved in all
      patients and was maintained at final follow up. CONCLUSION: Modified paediatric
      laser DCR appears to be an encouraging technique for primary nasolacrimal duct
      obstruction unresponsive to probing. This may be attributable to the modification
      of excision of mucous membrane, which may prevent regrowth.

PMID- 15846386
TI  - Risk of solar retinopathy: evaluation of newspaper warnings prior to the 2004
      Transit of Venus.

PMID- 15846385
TI  - Hormone replacement therapy and cataract: a population-based case-control study.
AB  - PURPOSE: Laboratory studies have suggested that hormone replacement therapy (HRT)
      may protect against the development of cataract, but epidemiological studies in
      humans have thus far been inconclusive. The aim of this study was to assess the
      association between hormone replacement therapy and cataract. METHODS: Population
      based case-control study using data from the General Practice Research Database
      in the UK. Participants were 10 000 women aged 45 years and over with diagnosed
      cataract and 10 000 controls matched on age, general practice, and calendar
      period. RESULTS: The crude odds ratio for the association between cataract and
      ever-use of oestrogen-only hormone replacement therapy was 1.13 (95% CI 0.99
      1.29). This reduced to 0.81 (95% CI 0.71-0.94) after adjustment for consultation
      rate. Similarly, the crude odds ratio for the association between cataract and
      ever-use of a formulation containing oestrogen and progestogen was 1.18 (95% CI
      1.01-1.39), reducing to 0.86 (95% CI 0.72-1.02) after adjustment for consultation
      rate. CONCLUSIONS: Oestrogen-only and oestrogen-progestogen hormone replacement
      therapies are associated with a small reduced risk of cataract. This data adds to
      the growing body of evidence on the effects of HRT on health. All potential
      benefits and risks of this therapy should be taken into account when considering
      its use.

PMID- 15846387
TI  - Tailoring pan-retinal photocoagulation for the haemianopic patient.

PMID- 15846388
TI  - Effect of illumination on visual function after monofocal and multifocal
      intraocular lens implantation.
AB  - PURPOSE: To compare best-corrected visual acuity (BCVA) and contrast sensitivity
      (CS) under different levels of illumination in patients who had monofocal and
      multifocal intraocular lenses (IOLs) and to establish the effect of different
      lighting conditions on vision in the two groups of patients. METHODS: We
      retrospectively reviewed 27 patients who underwent phacoemulsification for age
      related cataract and IOL implantation of either monofocal (SI30NB; n=10, 37%) or
      multifocal (SA40N; n=17, 63%) IOLs. Binocular distance and near BCVA and CS were
      tested using logMAR and Pelli-Robson charts that were externally illuminated with
      20, 200, 400, and 1600 lux, and were compared using repeated-measures analysis of
      variance. A questionnaire was administered to establish the lighting preference
      in the two groups and the effect of lighting conditions on their vision. RESULTS:
      Binocular distance and near BCVA and CS significantly increased with increasing
      illumination from 20 to 200 lux in the monofocal (mean=0.04 vs -0.07; P=0.006;
      0.37 vs 0.26, P=0.002 and 1.47 vs 1.60, P=0.01) as well as in the multifocal
      group (mean=0.03 vs -0.12, P<0.001; 0.38 vs 0.23, P<0.001 and 1.47 vs 1.61,
      P=0.002). No significant difference in BCVA or CS was found between the two
      groups at any of the four illumination levels. Both groups had similar lighting
      preference, but 43.8% of patients in the multifocal group experienced subjective
      worsening of their vision in bright outdoor lights. CONCLUSIONS: Distance and
      near BCVA and CS improve with increasing illumination in patients with monofocal
      and multifocal IOLs, but remain comparable in the two groups under common levels
      of indoor illumination. Patients with multifocal IOLs may experience worsening of
      their vision in bright outdoor lights.

PMID- 15846389
TI  - Immunoreactivity for c-kit and p63 as an adjunct in the diagnosis of adenoid
      cystic carcinoma of the breast.
AB  - Adenoid cystic carcinoma of the breast represents a unique clinicopathologic
      entity with a variable histological appearance and a relatively indolent clinical
      course in most of the cases. Adenoid cystic carcinoma may be difficult to
      differentiate from infiltrating duct carcinomas, and in particular from tubular
      and cribriform carcinomas, especially in core or vacuum-assisted biopsies. We
      evaluated the prevalence of c-kit, p63, and e-cadherin immunoreactivity in a
      series of 20 adenoid cystic carcinomas, comparing the results with those obtained
      in a series of infiltrating tubular carcinomas and infiltrating cribriform
      carcinomas. The hormone receptor status, proliferation labeling index, and HER/2
      immunoreactivity had been previously investigated in all the cases. Three (15%)
      adenoid cystic carcinomas and all infiltrating tubular and cribriform carcinomas
      showed estrogen receptor and/or progesterone receptor immunoreactivity (P <
      0.00001 for estrogen and P = 0.00002 for progesterone receptors). Adenoid cystic
      carcinomas consistently lacked any immunoreactivity for HER/2, whereas three
      (15%) infiltrating and cribriform carcinomas showed weak and incomplete membrane
      staining (P = 0.23077). Membranous immunoreactivity for c-kit was found in all
      except one (predominantly basaloid) adenoid cystic carcinomas (95%), and in none
      of the infiltrating tubular and cribriform carcinomas (P < 0.00001). Nuclear
      immunoreactivity for p63 was found in all except three (predominantly basaloid)
      adenoid cystic carcinomas (85%) and in none of the infiltrating tubular and
      cribriform carcinomas (P < 0.00001). All infiltrating tubular and cribriform
      carcinomas and 18/20 (90%) adenoid cystic carcinomas showed immunoreactivity for
      e-cadherin (P = 0.48718). In summary, adenoid cystic carcinomas showed the
      following phenotype: estrogen receptor-/progesterone receptor-/c-kit+/p63+ (13
      cases, 65%), estrogen receptor-/progesterone receptor/c-kit+/p63- (three cases,
      15%), estrogen receptor-/progesterone receptor-/c-kit-/p63+ (one case, 5%),
      estrogen receptor+/progesterone receptor+/c-kit+/p63+ (two cases, 10%), and
      estrogen receptor+/progesterone receptor-/c-kit+/p63+ (one case). By contrast,
      all the infiltrating tubular and cribriform carcinomas showed the estrogen
      receptor+/progesterone receptor+/c-kit-/p63- phenotype. Our data provide evidence
      that immunoreactivity for c-kit and/or p63 may be useful in differentiating
      adenoid cystic carcinomas from other types of breast cancer.

PMID- 15846390
TI  - Chorioamnionitis is associated with placental transmission of human
      immunodeficiency virus-1 subtype E in the early gestational period.
AB  - The frequency and the cellular basis for HIV-1 transmission from mother to child
      in the early gestational period are poorly understood. We compared the placentas
      of 24 women seropositive for HIV-1 subtype E and who had not received any
      antiretroviral drugs, to placentas of 25 seronegative women. All placentas were
      obtained during therapeutic abortion at 6-23 weeks gestation. Placentas and fetal
      organs were examined by routine light microscopy, immunostaining for p24 capsid
      protein, and in situ PCR to localize which cells were infected with HIV-1 subtype
      E. The number of previous abortions was not a factor in placental HIV infection
      since this number was higher in seronegative women (P < 0.01). There were no
      significant differences between the placentas of the two groups with respect to
      presence of chorioamnionitis, villitis, villous stromal fibrosis, infarction,
      abnormal villous maturation, deciduitis or decidual necrosis. HIV-1 subtype E was
      detected in up to 83% of placentas, either by immunostaining or in situ PCR, in
      trophoblast, villous stromal cells, Hofbauer cells, decidual and decidual
      glandular epithelium. Fetal organs were positive for HIV in 30% (6/20) of cases.
      There was a significant association between transmission of HIV to the fetus and
      the histologic findings of chorioamnionitis, plasmacellular deciduitis and
      decidual cell necrosis. This is the first report showing an association of
      chorioamnionitis with early in utero transmission of HIV-1 subtype E. This may
      help explain the cases of in utero transmission that persist despite
      antiretroviral prophylaxis, given that therapy is started in the late gestational
      period.

PMID- 15846391
TI  - Prevalence and prognostic significance of microsatellite alterations in young
      patients with bladder cancer.
AB  - Mutations in microsatellite sequences are a hallmark of neoplastic transformation
      and have been reported in the majority of human cancers. Conflicting results have
      been reported on the role of microsatellite alterations in bladder tumorigenesis
      and it has been suggested that they might be mainly involved in the development
      of bladder cancers in young patients. In this study, DNA was extracted from laser
      microdissected samples of 51 superficial papillary bladder urothelial carcinomas
      arising in young patients and was analyzed for the status of 19 microsatellite
      loci previously reported to be associated with bladder tumorigenesis. The
      occurrence and the pattern of microsatellite alterations, in form of loss or
      length variation, was evaluated and correlated with other clinicopathologic and
      molecular markers. The prognostic significance of these alterations was also
      evaluated. Loss of heterozygosity at one or more loci was detected in all 51
      tumors analyzed. Length variation in at least one locus was observed in 48 (94%)
      of the cases. The microsatellite that was more frequently altered was D11S488
      (69%), followed by D9S162 (61%), D3S3050 (55%), D3S1300 (51%) and D4S243 (51%),
      all the remaining being altered in less than 50% of cases. The occurrence of
      microsatellite alterations was not associated with tumor grade nor with tumor
      stage, the expression of p53, cyclin D1 or the cyclin-dependent kinase-inhibitor
      p27Kip1 while it was significantly more frequent in tumors with increased
      expression of the proliferation marker MIB-1 (P=0.003). The occurrence of
      alterations at the analyzed loci was associated with a reduced risk of tumor
      recurrence (P=0.04 by log-rank test) and disease progression (P=0.02) in a
      univariate analysis. These findings demonstrate that microsatellite alterations
      are frequent and early events and might have a prognostic significance in bladder
      cancers arising at young age.

PMID- 15846392
TI  - Securin is overexpressed in breast cancer.
AB  - Securin regulates sister chromatid separation during mitosis, induces bFGF
      mediated angiogenesis, and securin overexpression causes in vitro transformation
      and in vivo tumor formation in nude mice. As estrogen administration to
      oophorectomized rats increased pituitary securin expression, we used
      immunohistochemistry to examine securin and estrogen receptor alpha (ER-alpha)
      expression in 90 breast tumors and 18 normal breast tissues. Breast tumor securin
      and ER-alpha expression were quantitated by image analysis and expressed as fold
      difference relative to securin expression in normal breast tissue. Low
      cytoplasmic securin expression was seen in the normal breast epithelium, whereas
      abundant cytoplasmic and nuclear securin expression was demonstrated in all 90
      breast tumors. Highest securin expression was seen in brain metastatic breast
      tumors (4.3-fold, P<0.01), cells derived from metastatic breast cancers (6.5
      fold, P<0.001), and in invasive ductal carcinoma (mean+/-s.e.: 3.8-fold,
      P<0.001). Highly pleomorphic (4.1-fold) or highly proliferative breast tumors
      (1.6-fold) exhibited high immunohistochemical securin expression compared to low
      grade breast tumors (P<0.05). Northern blot analysis in 12 of the breast tumors
      confirmed the immunohistochemical findings demonstrating increased securin mRNA
      expression compared to normal breast mucosa (2.5-fold, P=0.03), with highest
      securin evident in invasive (3.5-fold) vs noninvasive tumors (1.9-fold, P=0.03).
      In addition, some tumors that exhibited high securin expression also expressed
      high ER-alpha levels (P<0.0001). These results demonstrate that the estrogen
      induced transforming gene, securin is abundantly expressed in breast carcinoma,
      and is associated with the presence of metastatic spread, and lymph node
      invasion. We propose immunohistochemical tumor securin expression as a potential
      invasive marker, and novel therapeutic target in breast cancer.

PMID- 15846393
TI  - Musculoskeletal responses of 2-year-old Thoroughbred horses to early training. 5.
      Kinematic effects.
AB  - AIM: To examine the effect of race training on kinematic parameters of the trot
      in a sample of 2-year-old Thoroughbred fillies. METHODS: Two-year-old
      Thoroughbred fillies that had been either trained for racing (n=7) or left
      untrained in small paddocks (n=7) were examined for lameness, and linear and
      temporal kinematic data were collected from video recordings of each horse
      trotted in-hand, 5, 9 and 13 weeks after the beginning of training. Horses were
      graded as: sound (Grade 0), suspected but not obviously lame (Grade 1), or
      definitely lame at the trot (Grade 2). RESULTS: Mean velocity at the trot did not
      vary with lameness grade. Compared with horses classified as sound (Grade 0),
      horses classified as suspected or definitely lame (Grades 1 and 2) had shorter
      (2.55 (SE 0.02) vs 2.41 (SE 0.02) and 2.44 (SE 0.03) m; p<0.001) and faster (671
      (SE 3) vs 645 (SE 1) and 647 (SE 4) msec; p<0.001) strides. None of the linear or
      temporal parameters measured varied significantly between the successive
      observation periods. When data from sound horses were pooled, the training group
      trotted at a higher mean velocity (4.22 (SE 0.08) vs 3.22 (SE 0.06) m/sec;
      p<0.001) and with a longer stride length (2.79 (SE 0.05) vs 2.18 (SE 0.06) m;
      p<0.001) than the untrained group. The stride duration was longer (669 (SE 7) vs
      662 (SE 9) msec; p=0.01), stance period was shorter (34.1 (SE 0.6) vs 39.3 (SE
      0.7) %; p<0.001) and mid-stance was achieved earlier in the stride (12.1 (SE 0.6)
      vs 13.1 (SE 0.2) %; p=0.001) in the trained than the untrained group. A longer
      swing phase in the trained group was associated with an increase in retraction
      time (9.2 (SE 0.2) vs 7.6 (SE 0.3) %; p=0.001). CONCLUSIONS: These data indicate
      that early race training in young Thoroughbreds was associated with quantifiable
      changes in linear and temporal kinematic parameters of the trot, which were
      related to the race-training objective of improving the horse's ability to work
      at higher velocities. CLINICAL RELEVANCE: Race training resulted in changes in
      the gait of non-lame horses at the trot, which should be considered during
      veterinary lameness examinations.

PMID- 15846394
TI  - Musculoskeletal responses of 2-year-old Thoroughbred horses to early training. 6.
      Bone parameters in the third metacarpal and third metatarsal bones.
AB  - AIM: To determine the effect of a known training regimen on the size and mineral
      content of the third metacarpal (Mc3) and third metatarsal (Mt3) bones of 2-year
      old Thoroughbred horses trained on racetracks. METHODS: Mc3 and Mt3 of seven
      horses trained on grass and sand tracks were scanned at several sites using
      conventional quantitative and peripheral computed tomography (CT). Bone
      dimensions and density in the diaphysis and epiphysis were compared with those
      from seven untrained horses. Calcein label was injected in two clusters, during
      Weeks 9 and 12. The extent and rate of diaphyseal modelling was determined by
      confocal fluorescent microscopic examination of thin plane parallel sections of
      the mid-metacarpal region. RESULTS: Volumetric bone mineral density (BMDv) of the
      epiphysis was markedly higher and of the diaphysis was slightly higher in trained
      compared with untrained horses, but greater bone size in the trained horses had
      the greatest effect on an index of bone strength. Active osteons, defined as
      Haversian systems containing calcein label, were fewer, of smaller diameter at
      the time of calcein injection, and had a greater bone apposition rate in trained
      than in untrained horses. CONCLUSIONS: Conventional training of 2-year-old
      Thoroughbred racehorses over a 13-week period had a significant effect on bone
      size, density and strength index when compared to untrained horses. CLINICAL
      RELEVANCE: Bone responded rapidly to early training. The data provide reference
      values and sites for use in longitudinal studies of commercial training regimens.

PMID- 15846395
TI  - Musculoskeletal responses of 2-year-old Thoroughbred horses to early training. 7.
      Bone and articular cartilage response in the carpus.
AB  - AIM: To describe features of the morphology of the carpus, quantify the thickness
      of hyaline and calcified cartilage, and to describe the morphology and density of
      subchondral bone in the third carpal bone (C3) of young Thoroughbred horses in
      early training. METHODS: C3 of seven 2-year-old horses in training and seven
      untrained horses matched for age, sex and breed were assessed by gross
      appearance, computed tomography, fine-structure radiography, image analysis of
      high-resolution photographs, and histology. RESULTS: Macroscopic lesions in
      cartilage were few and mild, and not significantly different between groups. High
      bone mineral density (BMD), in some cases typical of cortical bone, was confined
      to the dorsal load path, and was significantly higher in trained than in
      untrained horses (p<0.01). In the most dorsoproximal aspect of the radial
      articular facet, apparently outside the dorsal load path, the BMD in both trained
      and untrained horses was significantly less than in other regions of interest
      (ROIs). Adaptive increase in density was associated with thickening of the
      (junctions of) trabeculae oriented proximo-distally. Hyaline cartilage was
      thicker (p<0.001) in the concavity of the radial articular facet than dorsal or
      palmar to it, and was thicker in the trained than untrained group (p=0.007). No
      such differences were detected in the thickness of articular calcified cartilage
      (ACC). CONCLUSIONS: The rapid response of bone in C3 to relatively small amounts
      of high-speed exercise was confirmed. A previously unreported increase in
      thickness of hyaline cartilage was evident, perhaps indicating that this tissue
      may be more responsive than hitherto thought, at least to particular types of
      exercise at particular times. These changes occurred with little evidence of
      abnormality, and thus appeared to be adaptive to the exercise regimen. The model
      developed should be used for further definition of the exercise stimulus required
      to produce adaptive, protective changes in sites susceptible to athletic injury.
      CLINICAL RELEVANCE: The data will serve as reference for use in subsequent
      imaging studies in which sophisticated aids such as magnetic resonance imaging
      (MRI) may be used to predict carpal lesions.

PMID- 15846396
TI  - Musculoskeletal responses of 2-year-old Thoroughbred horses to early training. 8.
      Quantitative back-scattered electron scanning electron microscopy and confocal
      fluorescence microscopy of the epiphysis of the third metacarpal bone.
AB  - AIM: To characterise and explain the increase in density evident by computerised
      tomography (CT) and radiography in companion studies as a response to training,
      in bone in the palmar and dorsal regions of the condyles of the third metacarpal
      bone (Mc3) of 2-year-old Thoroughbred horses. METHODS: Compositional back
      scattered electron (BSE) imaging in scanning electron microscopy (SEM) and
      confocal scanning laser microscopy (CSLM) were conducted on polymethyl
      methacrylate (PMMA)-embedded mediolateral slices of the right distal Mc3 from
      seven 2-year-old Thoroughbred horses trained on a racetrack and seven untrained
      horses kept at pasture. One left Mc3 from each group was studied in transverse
      section planes. This study focussed on regions of Mc3 found to differ in density
      between the trained and untrained horses in companion studies using CT and
      radiography. RESULTS: The increase of bone density in the condyles of Mc3 in
      trained horses compared with untrained horses occurred, without prior
      osteoclastic resorption, via the deposition of new bone on pre-existing internal
      surfaces. Within prior marrow spaces of cancellous bone, there was also rapid
      formation of immature strands and fronds of bone which were more cellular and
      mineralised, and more lamellar bone tissue was deposited on these new scaffolding
      elements in the trained horses. Both resulted in increased bone volume fraction
      (BVF). The microscopic mineralisation density of the bulk of the new tissue was
      lower than in pre-existing bone, and CT and radiography underestimated the
      increase in BVF. The new tissue was thus probably less stiff at the microscopic
      scale than pre-existing bone, though its addition would stiffen the global
      structure. CONCLUSIONS: In Mc3 of all the trained horses, there were obvious
      differences in microscopic structure compared with those from the untrained
      horses. Moderate, industry-standard levels of exercise used to prepare young
      horses for racing induced the formation of new bone in non-bone spaces in bone
      tissue, such that the bone organ should better withstand later increased levels
      of exercise.

PMID- 15846397
TI  - Conjunctival vaccination of the brushtail possum (Trichosurus vulpecula) with
      bacille Calmette-Guerin.
AB  - AIM: To determine the efficacy of conjunctival vaccination of captive brushtail
      possums (Trichosurus vulpecula) with bacille Calmette-Guerin (BCG), as measured
      by immunological responses to vaccination and response to intratracheal challenge
      with Mycobacterium bovis. METHODS: Nine adult male brushtail possums were
      vaccinated by the instillation of a suspension of BCG strain Pasteur 1173P2 into
      the conjunctival sac of each eye. Each drop contained approximately 2.5 x 105
      colony forming units (cfu). At 8 weeks post-vaccination (pv) the vaccinated
      possums and 10 unvaccinated possums were challenged by intratracheal instillation
      of approximately 100 cfu of M. bovis. Cellular immune responses to bovine
      purified protein derivative (PPD) antigen were measured using the lymphocyte
      proliferation assay (LPA). Possums surviving to 50-51 days after challenge were
      euthanised and subjected to detailed post-mortem examination, including
      histopathology, to assess protection against tuberculosis. Sections of lung and
      spleen were cultured for M. bovis. RESULTS: No conjunctival inflammation or other
      adverse reactions to the administration of the vaccine were evident
      macroscopically. The vaccinated group showed a systemic cellular immune response
      to bovine PPD antigen at 4 and 8 weeks pv, and the response at 8 weeks was
      significantly greater than at 4 weeks (p<0.05). Conjunctival vaccination induced
      significant levels of protective immunity, measured as less mass of tuberculous
      lesions in lung (p<0.05) and less dissemination of disease in vaccinated compared
      with unvaccinated possums (p<0.05). CONCLUSIONS: Conjunctival vaccination with
      BCG induced a significant level of protective immunity against M. bovis infection
      in possums. This route of vaccination, together with intranasal aerosol
      vaccination, could be utilised in the delivery of an aerosolised vaccine using a
      device that sprays the vaccine suspension into the eyes and nose of possums.

PMID- 15846398
TI  - Impact of molybdenum on the copper status of red deer (Cervus elaphus).
AB  - AIM: To determine the effect of increasing molybdenum (Mo) intakes on serum and
      liver copper (Cu) concentrations and growth rates of grazing red deer (Cervus
      elaphus). METHODS: Molybdenum- and Cu-amended fertilisers were applied to six 1.1
      ha paddocks in a 3 x 2 design. Three levels of Mo were applied on two paddocks at
      each level in mid April (designated Day 1); levels were: none (control), 0.5
      (medium) and 1.0 (high) kg Mo/ha as sodium molybdate. In late May (Day 39), two
      levels of Cu (none and 3.0 kg Cu/ha, as copper sulphate) were applied to each of
      the three levels of Mo-treated paddocks. Pasture Mo, Cu and sulphur (S)
      concentrations were measured at about fortnightly intervals. In late June (Day
      74), ten 6-month-old red deer hinds were placed on the six experimental pastures,
      and serum and liver Cu concentrations were monitored at about monthly intervals
      for 102 days. The hinds were weighed on four occasions during the trial. RESULTS:
      Mean pasture Mo concentrations on Day 56 were 2, 4.6 and 11.3 mg/kg dry matter
      (DM) for the untreated control, medium and high Mo-treated pastures,
      respectively. Pasture Cu concentration was 95 mg/kg DM on Day 59, 53 mg/kg DM on
      Day 90, and 9 mg/kg DM by Day 153. Mean S concentration in pasture was 3.3 (range
      3.03-3.45) g/kg DM. Copper application to pasture had no significant effect on
      serum and liver Cu concentrations in deer so data were pooled within Mo
      treatment. Mean initial (Day 74) serum Cu concentration was 9.2 micromol/L. In
      the deer grazing the control Mo pasture, this increased to 10.3 micromol/L on Day
      112, before decreasing to 6.4 micromol/L on Day 176. In deer grazing the medium
      and high Mo-treated pastures, mean serum Cu concentrations were 3.8 and 3.9
      micromol/L, respectively, on Day 112, and 2.5 and 3.3 micromol/L, respectively,
      on Day 176. Mean initial (Day 74) liver Cu concentration was 131 micromol/kg
      fresh tissue. In the deer grazing the control Mo pasture, this declined to 120
      and 52 micromol/kg on Days 112 and Day 176, respectively. In deer grazing the
      medium and high Mo-treated pastures, liver Cu concentrations decreased to 55 and
      52 micromol/kg fresh tissue, respectively, on Day 112, and 21 and 20 micromol/kg
      fresh tissue, respectively, on Day 176. Mean serum and liver Cu concentrations
      were not significantly different between deer grazing the medium and high Mo
      treated pastures, and were lower (serum p=0.003, liver p<0.001) in those groups
      than in deer grazing the untreated control pastures. No clinical signs of Cu
      deficiency associated with lameness were observed. Deer grazing pastures that had
      Mo concentrations >10 mg/kg DM had lower (p=0.002) growth rates (100 vs 130
      g/day) than those on pastures containing <2.4 mg Mo/kg DM. CONCLUSION: Increasing
      pasture Mo concentrations from 2 mg/kg DM to > or =4.6 mg/kg DM significantly
      reduced serum and liver Cu concentrations in grazing deer. Reduced growth rate
      was observed at pasture Mo concentrations >10 mg/kg DM.

PMID- 15846399
TI  - Associations between pregnancy outcome and serological response to Neospora
      caninum among a group of dairy heifers.
AB  - AIM: To monitor pregnancy in a group of rising 2-year-old dairy heifers on a farm
      on which abortion due to Neospora caninum was known to occur in previous years.
      METHODS: A prospective cohort study group of 164 rising 2-year-old heifers was
      pregnancy-tested and blood-sampled at 4-5-week intervals throughout gestation.
      Sera were tested for antibodies to N. caninum at 3-4-month intervals, using an
      enzyme-linked immunosorbent assay (ELISA). When loss of pregnancy was detected,
      an N. caninum indirect fluorescent antibody test (IFAT) was conducted
      retrospectively on stored sera collected the month before abortion, the month
      abortion was detected, and for the following 2 months, from heifers that aborted.
      All fetal and placental material detected following abortion was subjected to
      gross post-mortem and histopathological examination. RESULTS: Eleven of 18 (61%)
      heifers that were seropositive and 4/146 (3%) heifers that were seronegative to
      N. caninum by ELISA, aborted. The relative risk for abortion among ELISA-positive
      heifers was 23.6. Abortion occurred predominantly between Days 120 and 152
      gestation among the ELISA-positive heifers and throughout gestation among the
      ELISA-negative heifers. IFAT titres rose around the time of abortion in most of
      the heifers that were previously seropositive by ELISA, but dropped rapidly again
      in post-abortion samples. IFAT titres among 4/6 ELISA-positive heifers that did
      not abort increased, but later in gestation than the time other heifers aborted.
      IFAT titres remained negative in heifers that aborted that were ELISA negative.
      CONCLUSIONS: Heifers that were seropositive to N. caninum by ELISA had a much
      greater risk of abortion than seronegative heifers. Most seropositive heifers
      showed evidence of a reactivation of infection during pregnancy. High (> or
      =1:2,000) N. caninum IFAT titres also occurred in non-aborting heifers. CLINICAL
      RELEVANCE: Culling of replacement heifers seropositive to N. caninum may be a
      cost-effective strategy for minimising risk of abortion. Pregnancy testing
      heifers before 5 months gestation may overestimate the number that calve in N.
      caninum-infected herds, but would assist in documenting the occurrence of
      abortion. Reliance on a high (>1:2,000) IFAT titre to rule-in N. caninum as a
      cause of abortion is likely to produce false-positive results.

PMID- 15846400
TI  - A serial cross-sectional study of the prevalence of rabbit haemorrhagic disease
      on three farms in the lower North Island of New Zealand.
AB  - AIM: To estimate over a 3-year period following the first release of rabbit
      haemorrhagic disease virus (RHDV) the prevalence of rabbit haemorrhagic disease
      (RHD) and the abundance of rabbits (Oryctolagus cuniculus) in an area that
      historically had low rabbit densities. METHODS: Three farms grazing predominantly
      sheep and beef cattle, located close together and with low initial rabbit
      densities, were selected for study. RHDV had been deliberately released on all
      farms in December 1997. Farms were visited 2-3 times per year between June 1998
      and April 2001. At each visit, rabbits were shot with the aid of spotlights at
      night and blood samples were collected for detection of RHDV antibodies. Rabbit
      carcasses were necropsied and the age of the animals was determined. Rabbit
      abundance on each property was measured throughout the study using spotlight
      night counts. Logistic regression was used to identify factors associated with
      the risk of carcasses being seropositive for RHDV. RESULTS: Rabbit density
      differed initially between farms (8.2, 9.9, 2.3 rabbits per spotlight km in June
      1998), and declined on all three properties over time (1.2, 2.4, 1.1 rabbits per
      spotlight km in November 2000). Highest antibody titres to RHDV were initially
      evident on the farm on which rabbits were most abundant. The average prevalence
      of seropositive rabbits overall was 21% (95% CI=15-28%). Female rabbits tended to
      be less likely to be seropositive for RHDV than males (OR=0.47; 95% CI=0.21
      1.02). The odds of becoming seropositive were reduced for rabbits born in the
      breeding season of 1999-2000 (OR=0.17; 95% CI=0.05-0.64). CONCLUSIONS: The
      temporal pattern of outbreaks measured by peaks of seroprevalence differed
      between closely-spaced farms when they had different rabbit densities, but were
      similar when rabbit densities were similar. Microclimate and vegetation
      influencing abundance of insect vectors for RHDV and intrinsic population-related
      factors like rabbit breeding behaviour are also likely to be involved in local
      patterns of spread.

PMID- 15846402
TI  - Pancreatic cyst in a cat.
AB  - CASE HISTORY: A 5-year-old neutered male Cornish Rex cat was presented for
      evaluation with a history of vomiting over the previous 5 days. CLINICAL
      FINDINGS: An abdominal mass was palpated, which was shown to be cystic by
      ultrasound examination. Exploratory surgery revealed this to be associated with
      the pancreas and it was duly resected. Histopathology was performed on the cystic
      mass. DIAGNOSIS: Pancreatic cyst with associated chronic active inflammation.
      CLINICAL RELEVANCE: This is the first report of a true pancreatic cyst in a cat.

PMID- 15846401
TI  - Surface-active phospholipid (surfactant) in equine tendon and tendon sheath
      fluid.
AB  - AIM: To investigate the presence of surface-active phospholipid (SAPL, or
      surfactant) in equine tendon and tendon sheath fluid. METHODS: The left front
      flexor tendon and sheath were removed from five Thoroughbred horses. Phospholipid
      was extracted from tendon sheath fluid using Folch reagent and quantified using
      spectroscopy. Transmission electron microscopy (TEM) was used to observe the
      tendon surfaces. RESULTS: The presence of phospholipid (90.6 (SD 4.3) microg/ml)
      in tendon sheath fluid, plus the appearance of oligolamellar layers and lamellar
      bodies on the tendon surface were indicative of SAPL. CONCLUSIONS: Evidence of
      SAPL was found in equine tendon, and may have a similar lubricating function as
      reported for synovial joints. CLINICAL RELEVANCE: These findings may have
      important implications for normal tendon function and possible therapeutic
      adjuncts for tendon and tendon sheath injuries.

PMID- 15846403
TI  - Diplodia maydis: a cause of death of cattle in Argentina.
AB  - CASE HISTORY: This report describes an outbreak of high mortality of heifers
      after they consumed harvested maize fields parasitised with the fungus Diplodia
      maydis. CLINICAL FINDINGS: Clinical signs observed were generalised muscle
      tremors, incoordination, ataxic hindquarters, paralysis and death. The morbidity
      of the outbreak was 27/500 (5.4 %) and mortality 10/27 (37%). No gross lesions
      were observed, however histopathological examination revealed moderate to severe
      degeneration of myelin shafts in the white matter of the cerebellum. Diplodia
      maydis infection of maize was identified from visual characteristics of mycelia
      and pycnidia. DIAGNOSIS: Diplodia toxicity (diplodiosis). CLINICAL RELEVANCE:
      This is the first description of the poisoning of cattle by maize contaminated
      with D. maydis in Argentina, where feeding cattle on harvested maize fields is
      common practice. It is possible this disease could occur in other countries, like
      New Zealand, where this fungus is known to be present.

PMID- 15846404
TI  - An acute outbreak of teat lesions affecting 38% of a dairy herd in Northland.

PMID- 15846405
TI  - Detection of RNA nucleobase metalation by NMR spectroscopy.
AB  - Nucleic acids possess several metal cation recognition sites, including
      phosphates, nucleobases and possibly riboses. This article focuses on the
      detection of nucleobase-metal interactions by NMR spectroscopy.

PMID- 15846406
TI  - Motor protein nano-biomachine powered by self-supplying ATP.
AB  - A new nano-biomachine has been created from microtubules (MTs) and hetero
      bifunctional polymer particles bearing pyruvate kinase, which is propelled on
      glass surfaces coated with kinesin by use of self-supplying ATP.

PMID- 15846407
TI  - Synthesis, structure and magnetic properties of a trinuclear [Mn(III)Mn(II)2]
      single-molecule magnet.
AB  - Ferromagnetic exchange between the three Mn ions in the complex
      [Mn3(Hcht)2(bpy)4](ClO4)3 leads to a spin ground state of S = 7; single crystal
      studies reveal the temperature and sweep rate dependent hysteresis loops expected
      for a single-molecule magnet.

PMID- 15846408
TI  - The search for 3d-4f single-molecule magnets: synthesis, structure and magnetic
      properties of a [Mn(III)2Dy(III)2] cluster.
AB  - Tetranuclear [Mn(III)2Ln(III)2] complexes formed using tripodal ligands display
      frequency dependent out-of-phase ac susceptibility signals and temperature and
      sweep rate dependent hysteresis loops.

PMID- 15846409
TI  - One-pot tandem living radical polymerisation-Huisgens cycloaddition process
      ("click") catalysed by N-alkyl-2-pyridylmethanimine/Cu(I)Br complexes.
AB  - Azide terminally functional poly(methyl methacrylate)s (Mn = 4000-6000, PDI =
      1.21-1.28) have been prepared by living radical polymerization and successfully
      reacted with alkynes in a Huisgen cycloaddition (click) reaction in one pot using
      the same catalyst for both processes.

PMID- 15846410
TI  - The first example of a crystalline guest-free form of the tris(5-acetyl-3
      thienyl)methane (TATM) host material.
AB  - The first example of a guest-free crystalline form of tris(5-acetyl-3
      thienyl)methane (TATM), in both powder and single crystal form, was obtained by
      leaching water-soluble guests out of the guest-host inclusion compounds with
      acetone, ethanol and methanol.

PMID- 15846411
TI  - Terminal co-ligand directed synthesis of a neutral, non-interpenetrated (10,3)-a
      metal-organic framework.
AB  - A neutral, non-interpenetrated porous metal-organic framework (MOF) having (10,3)
      a topology, Cu(3,5-PDC)(DMF)(py), (DMF =N,N'-dimethylformamide, py = pyridine),
      has been constructed via the assembly of the achiral tri-connected building
      blocks 3,5-pyridinedicarboxylate (3,5-PDC) and CuN(CO2)2, synthesized in situ.
      Similarly, a 2D structure having (6,3) topology has been generated, each by means
      of terminal co-ligand directed synthesis.

PMID- 15846412
TI  - Formal encapsulation of [Fe(H2O)6](3+) by {Fe2(hpdta)} units gives a system of S=
      13/2 Fe(III)9 oxo clusters showing magnetic hysteresis.
AB  - Under solvothermal conditions the unprecedented nonanuclear Fe(III) aggregate
      [Fe9(mu3-O)4(mu-OH)4(hpdta)4]5- is formed through the formal encapsulation of
      [Fe(H2O)6]3+ by four [Fe2(hpdta)(H2O)2]+ units: the aggregates have ground state
      spins of S= 13/2 while the observed hysteresis below 1.8 K results from inter
      cluster antiferromagnetic coupling.

PMID- 15846413
TI  - Cyclopentane-modified PNA improves the sensitivity of nanoparticle-based
      scanometric DNA detection.
AB  - trans-Cyclopentane-modified PNA has been successfully utilized as a target
      capture strand to improve the detection limit of a known DNA detection assay, and
      provide high levels of mismatch discrimination.

PMID- 15846414
TI  - Microwave-assisted direct transformation of amines to ketones using water as an
      oxygen source.
AB  - Retro-reductive aminations, direct transformations of amines to ketones, were
      catalyzed by Pd/C in water under microwave irradiation.

PMID- 15846415
TI  - Anomaly of charge transport of an iodide/tri-iodide redox couple in an ionic
      liquid and its importance in dye-sensitized solar cells.
AB  - Fast charge transport based on the exchange reaction of an I(-)/I(3)(-) redox
      couple, which has been observed in ionic liquids due to their high ionic strength
      but not in molecular liquids, contributes to the high performance of dye
      sensitized solar cells using the ionic liquids in spite of their high viscosity.

PMID- 15846416
TI  - Synthesis of single-phase anatase nanocrystallites at near room temperatures.
AB  - Single-phase aqueous solutions of nanocrystalline anatase titanium dioxide were
      produced under ambient pressure and at a temperature as low as 38 degree C using
      the sol-gel process.

PMID- 15846417
TI  - Synthesis and photophysical characterization of a subphthalocyanine fused dimer
      C60 dyad.
AB  - Photophysical studies of a newly synthesized fused subphthalocyanine dimer-C60
      revealed a complex cascade of energy transfer events to succeed the initial SubPc
      dimer photoexcitation.

PMID- 15846418
TI  - Synthesis of multivalent aminoglycoside mimics via the Ugi multicomponent
      reaction.
AB  - The synthesis of multivalent neoglycoconjugates with 2,6-diamino-2,6
      dideoxyglucose is accomplished by a flexible Ugi multicomponent approach leading
      to mono-, di- and tri-valent carbohydrate clusters.

PMID- 15846419
TI  - A new Co(II)-metalloviologen-based electrochromic material integrated in thin
      multilayer films.
AB  - A metallosupramolecular coordination polyelectrolyte prepared by the reaction of
      cobalt(II) with a novel bisterpyridine ligand has been assembled as the active
      component in electrochromic films by sequential deposition using electrostatic
      layer-by-layer self-assembly.

PMID- 15846420
TI  - Straightforward synthesis of sulfur bridged oligopyrrolic macrocycles.
AB  - Di- and trisulfide linked oligopyrrolic macrocycles are obtained when appropriate
      alpha,alpha'-free pyrrolic precursors are reacted with sulfur dichloride; these
      systems represent the first examples of what might be a general new class of
      porphyrin analogues.

PMID- 15846421
TI  - Synthesis of ordered mesoporous carbons with channel structure from an organic
      organic nanocomposite.
AB  - Mesoporous carbons with ordered channel structure (COU-1) have been successfully
      fabricated via a direct carbonization of an organic-organic nanocomposite.

PMID- 15846422
TI  - First observation of the hyperfine structure of an excited quintet state in
      liquid solution.
AB  - After pulsed photoexcitation of a new fullerene-linked bisnitroxide, a well
      resolved transient EPR spectrum is detected which is assigned to an excited
      quintet spin state generated by spin coupling of the nitroxides and the fullerene
      excited triplet.

PMID- 15846423
TI  - Direct nanocomposite of crystalline TiO2 particles and mesoporous silica as a
      molecular selective and highly active photocatalyst.
AB  - Well-crystallised TiO2 particles (P-25, 20-30 nm in diameter) were directly
      incorporated into surfactant-templated mesoporous silica particles (pore
      diameter: 2.7 nm), and the composite material with a high TiO2 content (60 wt%)
      showed molecular selective and enhanced photocatalysis for decomposition of 4
      nonylphenol.

PMID- 15846425
TI  - Helical poly-L-glutamic acid templated nanoporous aluminium oxides.
AB  - The synthesis of porous aluminium oxide made in the presence of helical poly-L
      glutamic acid is reported.

PMID- 15846424
TI  - A recyclable catalyst for asymmetric transfer hydrogenation with a formic acid
      triethylamine mixture in ionic liquid.
AB  - A novel task-specific ionic ligand with an imidazolium salt moiety was
      synthesized, and its catalytic ability and recyclability for asymmetric transfer
      hydrogenation of acetophenone derivatives with a formic acid-triethylamine
      azeotropic mixture in an ionic liquid [bmim][PF6] was examined.

PMID- 15846426
TI  - Aragonite growth on single-crystal substrates displaying a threefold axis.
AB  - Aragonite was grown epitaxially under calcite-stable conditions by using
      carbonate free single-crystal substrates with a threefold axis oriented normal to
      the surface.

PMID- 15846428
TI  - Double layer properties of carbon aerogel electrodes measured by probe beam
      deflection and AC impedance techniques.
AB  - Probe beam deflection (PBD) and AC impedance are used to quantitatively evaluate
      the double layer properties of carbon aerogel electrodes in aqueous media (NaF).
      The measurements allow determination of the potential of minimum charge of the
      material.

PMID- 15846427
TI  - Generation dependent mesophase behavior in extended amphiphilic dendrons in the
      shape of macromolecular dumbbells.
AB  - Small angle X-ray scattering studies of 2nd and 3rd generation based extended
      amphiphilic dendrons in the shape of macromolecular dumbbells with identical
      hydrophilic volume fractions suggest 2-D hexagonal columnar and Pm3n micellar
      cubic mesophases, respectively, elucidating the role of shape induced interface
      curvature in mesophase formation.

PMID- 15846429
TI  - 1,2,4,5-Tetra([5]trovacenyl)benzene: an organometallic tetraradical displaying
      pronounced electro- and magnetocommunication.
AB  - The organometallic tetraradical 1,2,4,5-[(eta)7-C7H7)V(all eta]5-C5H4)]4C6H2 has
      been prepared and structurally characterized. The isotropic EPR spectrum displays
      29 a(51V) hyperfine lines, the intensity distribution slightly deviating from
      binomial. Exchange coupling therefore approaches the strong exchange limit,
      J(ortho) not equal to J(meta) not equal to J(para) greater or approximately 50
      a(51V) with a(51V)= 0.0067 cm(-1). According to magnetic susceptometry, the
      interaction is antiferromagnetic. While redox splittings deltaE(1/2) are resolved
      for the four reduction steps this is not the case for oxidation.

PMID- 15846430
TI  - Cyclopentadienyl titanium hydroxylaminato complexes as highly active catalysts
      for the polymerization of propylene.
AB  - Half sandwich complexes of titanium bearing eta1 or eta2 bound nitroxide ligands
      are highly active catalysts for the polymerisation of propylene to high molecular
      weight atactic poly(propylene).

PMID- 15846431
TI  - Unprecedented reversible coupling of alkynyl and phosphide ligands on a dinuclear
      platinum framework.
AB  - The reductive coupling of the bridging phosphide and the adjacent [sigma]-alkynyl
      moieties in [Pt2(mu-P(t)Bu2){mu,eta1:eta2-C(Ph)CH2}(C[triple bond]C
      Ph)(CO)(P(t)Bu2H)(Br)] is promoted by bromide abstraction and is reversed by
      adding N(n)Bu4Br.

PMID- 15846433
TI  - 1,3-Dithiole-2-thione derivatives featuring an anthracene unit: new selective
      chemodosimeters for Hg(II) ion.
AB  - New selective chemodosimeters for Hg(II) ion based on 1,3-dithiole-2-thione
      derivatives containing an anthracene unit are described.

PMID- 15846432
TI  - Isolation of a new two-dimensional honeycomb carbonato-bridged copper(II) complex
      exhibiting long-range ferromagnetic ordering.
AB  - Atmospheric CO2 fixation by an aqueous solution containing Cu(ClO4)2.6H2O and 4
      aminopyridine (4-apy) yields a novel example of a two-dimensional mu3-CO3 bridged
      copper(II) complex {[Cu(4-apy)2]3(mu3-CO3)2(ClO4)2.(1/2)CH3OH}n that has been
      characterized by IR, UV and X-ray crystallography; preliminary magnetic
      measurements show that complex exhibits long-range ordered ferromagnetic
      coupling.

PMID- 15846434
TI  - Rational synthesis of asymmetric bicyclic siloxane.
AB  - A rational and versatile method to synthesize bicyclosiloxane of design
      structures is presented. The method is used to synthesize a new, asymmetric
      bicyclo[7.5.3]octasiloxane and other bicyclosiloxanes.

PMID- 15846435
TI  - Synthesis of primary-alkyl selenols and selenides from primary-alkyl thiols
      involving diphenyl sulfonium salts.
AB  - Hexyl thiol has been transformed to hexyl selenol and related selenides and
      selenocyanate by substitution of the corresponding hexyldiphenylsulfonium
      tetrafluoroborate with selenium nucleophiles.

PMID- 15846436
TI  - Electrochemically deposited nanocomposite of chitosan and carbon nanotubes for
      biosensor application.
AB  - A simple and controllable electrodeposition method for the formation of a
      chitosan-carbon nanotube nanocomposite film on an electrode surface was proposed
      and further used for the construction of an electrochemical biosensor.

PMID- 15846437
TI  - Selective Ir-catalysed borylation of polycyclic aromatic hydrocarbons: structures
      of naphthalene-2,6-bis(boronate), pyrene-2,7-bis(boronate) and perylene-2,5,8,11
      tetra(boronate) esters.
AB  - The selectivity of the iridium boryl complex-catalysed reaction of pyrene and
      perylene with B2(pin)2 (pin = OCMe2CMe2O) has been employed in the synthesis of
      D(2h)-symmetry pyrene-2,7-(Bpin)2 and D(4h)-symmetry perylene-2,5,8,11-(Bpin)4
      providing direct borylation of positions which are otherwise difficult to
      derivatise.

PMID- 15846438
TI  - Efficient batch and continuous flow Suzuki cross-coupling reactions under mild
      conditions, catalysed by polyurea-encapsulated palladium (II) acetate and tetra-n
      butylammonium salts.
AB  - Suzuki cross-coupling reactions are effected in both conventional organic
      solvents, under continuous flow conditions at 70 degree C, and in batch mode in
      supercritical carbon dioxide (scCO2), at temperatures as low as 40 degrees C in
      the presence of palladium(II) acetate microencapsulated in polyurea [PdEnCat] and
      tetra-n-butylammonium salts.

PMID- 15846439
TI  - One-pot catalyst preparation: combined detemplating and Fe ion-exchange of BEA
      through Fenton's chemistry.
AB  - BEA zeolite has been simultaneously detemplated and Fe-exchanged by treating the
      parent zeolite with a Fenton's-type reagent (Fe3+-H2O2) at low temperature. This
      one-pot process simplifies and speeds up considerably the preparation route. The
      catalyst shows excellent performance on N2O decomposition compared to
      conventionally prepared Fe-BEA.

PMID- 15846440
TI  - Minimally invasive skills centers-Stanford University: how innovation impacts
      training.

PMID- 15846441
TI  - Against the tide: Kurt Karl Stephan Semm (1927-2003).

PMID- 15846442
TI  - Advances in the surgical treatment of fecal incontinence.
AB  - Although surgery for fecal incontinence has been shown to be effective, it is
      still very challenging and sometimes frustrating. Overlapping sphincteroplasty,
      by far the most common procedure, is effective in patients with sphincter
      defects; however, recent data suggest that success rates tend to deteriorate over
      time. A thorough preoperative evaluation incorporates numerous factors, including
      patient characteristics, severity of incontinence, type and size of the sphincter
      defect as assessed by physical examination, anal ultrasound, and anorectal
      physiology studies including anal manometry, electromyography, and pudendal nerve
      terminal motor latency assessment. The use of these evaluation methods has
      allowed better patient assignment for a variety of new alternative treatment
      options. Innovations in the surgical treatment of fecal incontinence range from
      simple, office-based sphincter augmentation techniques to surgical implantation
      of mechanical devices. This article reviews 5 alternative surgical treatment
      options for fecal incontinence: injection of carbon-coated beads in the submucosa
      of the anal canal, radiofrequency energy delivery, stimulated graciloplasty,
      artificial bowel sphincter, and sacral nerve stimulation.

PMID- 15846443
TI  - Laparoscopic splenectomy: what barriers remain?
AB  - Conditions that once were considered either relative or absolute
      contraindications for laparoscopic splenectomy have become fewer and less
      significant in the overall assessment of candidates for this procedure. Advances
      in surgical technique, operative conduct, and instrumentation have made it
      feasible to perform splenectomy laparoscopically with good outcomes and minimal
      morbidity in a variety of different pathologic conditions. Obesity, malignancy,
      pregnancy, and splenomegaly are assessed here in detail.

PMID- 15846444
TI  - A short-term delayed approach to laparoscopic ventral hernia when injury is
      suspected.
AB  - Laparoscopic repair is a safe and effective method for treating ventral hernias.
      Although the risk of bowel injury is low, its management is controversial. When
      injury is suspected or repaired, the risk of infection might prohibit a repair
      with prosthetic mesh. The timing of safe mesh placement is unclear. We
      retrospectively reviewed 9 patients from our prospective laparoscopic ventral
      hernia database who were treated with a 2- to 6-day delay in mesh placement due
      to violation of the gastrointestinal tract or risk of unidentified or delayed
      injury. All 9 patients had large ventral hernias from previous laparotomies
      (average defect, 399.4 cm2) and presented for elective repair. Three of the
      patients were morbidly obese, and one was diabetic. The decision to delay mesh
      placement was made intraoperatively. Reasons for delay were colotomy with repair,
      extensive serosal tears, resection after enterotomy, and resection for chronic
      small bowel obstruction. All patients received broad-spectrum antibiotics while
      awaiting definitive repair. In 7 patients, mesh was successfully placed between
      postoperative days 2 and 6. Delayed mesh placement failed in 2 patients due to
      loss of domain with bowel edema. The average length of stay was 9 days (range, 6
      to 15 days) and average follow-up was 136 days (range, 36 to 303 days). No early
      mesh infections or other major complications were reported. A short delay of 2 to
      6 days with antibiotic coverage is a safe strategy for managing potential or
      recognized injury to the gastrointestinal tract during laparoscopic ventral
      hernia repair.

PMID- 15846445
TI  - Does hyaluronic acid-carboxymethylcellulose (HA-CMC) membrane interfere with the
      healing of intestinal suture lines and abdominal incisions?
AB  - Although hyaluronic acid-carboxymethylcellulose (HA-CMC) membrane has the
      advantage of preventing intraabdominal adhesions, it has theoretical risk of
      negative effects on the healing of intestinal suture lines by forming a barrier
      between the suture lines and neighboring serosal surfaces. This study evaluated
      the effect of HA-CMC on bowel anastomoses, scar healing, and intraabdominal
      adhesion formation. Two groups of 10 male Sprague-Dawley rats were examined. In
      the first group, laparotomy was performed with a median incision. Colotomy on the
      cecum and a single-layer repair of the bowel wall was performed. HA-CMC membrane
      was placed on the cecal suture line and under the laparotomy incision before
      abdominal closure. The second group had the same procedure but no HA-CMC membrane
      was placed. The animals were killed on postoperative day 14. Intraabdominal
      adhesions, laparotomy suture line endurance, bursting pressure of the repaired
      cecal wall, and tissue hydroxyproline levels were determined. The repaired cecal
      wall was also examined histopathologically. The statistical analyses revealed
      that HA-CMC prevented intraabdominal adhesions significantly. No negative effects
      of this material on the healing of the bowel and laparotomy suture lines were
      observed. HA-CMC appears to be a safe material to prevent intraabdominal
      adhesions, without negative effects on the healing of abdominal incisions and
      bowel suture lines.

PMID- 15846446
TI  - A basis for electronic cognitive simulation: the heuristic patient.
AB  - Although medical trainees are expected to become expert quickly and safely,
      limited electronic methods are available to rehearse medical cognition for common
      outpatient and non-emergent inpatient problems. We conducted a series of formal
      observational sessions designed to determine what interaction requirements are
      desirable for student rehearsal of medical management by using an electronic
      patient. The studies utilized both manual and electronic methods for a student to
      evaluate and manage patients with medical and surgical problems. We observed the
      following major requirements for an effective simulation experience: the user
      must have a trial-and-error experience with the patient; the user must have
      unconstrained access to query and treat the patient; anatomic and physiologic
      values in the patient must change appropriately in response to user actions; and
      the user must be able to control certain time-related aspects of the simulation.
      When these requirements are implemented within a simulation, user-directed
      management of an electronic patient, by itself, becomes a strong aid to learning
      by trial- and-error techniques. We conclude that the heuristic patient is a
      practical and useful concept. Once fully developed, it would allow rehearsal of
      patient care decision making, intrinsically demonstrating trainee knowledge
      deficits, and resulting in self-directed learning.

PMID- 15846447
TI  - Evidence-based practice in laparoscopic surgery: perioperative care.
AB  - Best practices for reducing risks of postoperative infection, venous
      thromboembolism, and nausea and vomiting in patients undergoing laparoscopic
      surgery are uncertain. As a result, perioperative care varies widely. We reviewed
      evidence from randomized clinical trials on the effectiveness of interventions
      for postoperative infection, venous thromboembolism, and nausea and vomiting Data
      sources were the Cochrane Central Register of Clinical Trials, reference lists of
      published trials, and randomized clinical trials published in English since 1990.
      Trials were also limited to those focused on patients undergoing laparoscopic
      surgery. Data from 98 randomized clinical trials were included in the final
      analysis. Routine antibiotic use in laparoscopic cholecystectomy, and possibly
      other clean procedures not involving placement of prostheses, is likely
      unnecessary. Similarly, venous thromboembolism prophylaxis is probably
      unnecessary for low-risk patients undergoing brief procedures. Of a wide variety
      of methods for reducing postoperative nausea and vomiting, serotonin receptor
      antagonists appear the most effective and should be considered for routine
      prophylaxis.

PMID- 15846448
TI  - The argument for lightweight polypropylene mesh in hernia repair.
AB  - The development of polypropylene prosthetics revolutionized surgery for the
      repair of abdominal wall hernias. A tension-free mesh technique has drastically
      reduced recurrence rates for all hernias compared to tissue repairs and has made
      it possible to reconstruct large ventral defects that were previously
      irreparable. The repair of abdominal wall defects is one of the most commonly
      performed general surgical procedures, with over 1 million polypropylene implants
      inserted each year. Surprisingly, little research has been performed to
      investigate the interaction of abdominal wall forces on a ventral hernia repair
      or the required amount or strength of the foreign-body material necessary for an
      adequate hernia repair. The long-term consequences of implantable polypropylene
      prosthetics are not without concern. The body generates an intense inflammatory
      response to the prosthetic that results in scar plate formation, increased
      stiffness of the abdominal wall, and shrinkage of the biomaterial. Reducing the
      density of polypropylene and creating a ''light weight'' mesh theoretically
      induces less foreign-body response, results in improved abdominal wall
      compliance, causes less contraction or shrinkage of the mesh, and allows for
      better tissue incorporation. A review of the laboratory data and short-term
      clinical follow-up is reviewed to provide a strong basis or argument for the use
      of ''light weight'' prosthetics in hernia surgery.

PMID- 15846449
TI  - Effective training and assessment of surgical skills, and the correlates of
      performance.
AB  - This report briefly describes the University of Toronto Surgical Skills Centre
      and summarizes research in technical skills conducted at that site. This includes
      work on curriculum evaluation, the development and validation of assessment
      instruments, the retention of technical skills after training, and the prediction
      of success in surgery. These studies benefited from the large number of
      participants made available by the Surgical Skills Centre, allowing for
      randomized controlled studies or correlation studies where larger numbers are
      necessary for adequate statistical power. Recent emphasis has been on the further
      development of objective means of assessment and the exploration of correlates of
      surgical performance. Ongoing research is also aimed at simulator validation.

PMID- 15846450
TI  - Mental workload: a new parameter for objective assessment?

PMID- 15846451
TI  - Assessing mental workload during laparoscopic surgery.
AB  - Although the use of performance efficiency measures (speed, movement economy,
      errors) and ergonomic assessments are relatively well established, the evaluation
      of cognitive outcomes is rare. This report makes the case for assessment
      strategies that include mental workload measures as a way to improve training
      scenarios and training/operating environments. These mental workload measures can
      be crucially important in determining the difference between well-intentioned but
      subtly distracting technologies and true breakthroughs that will enhance
      performance and reduce stress.

PMID- 15846452
TI  - Bariatric surgery: assessing opportunities for value innovation.
AB  - Obesity has been increasing over the past two decades, and the amount of medical
      and media attention given to bariatric surgery as a promising option for morbidly
      obese individuals is growing. The growth of bariatric surgery also has been
      attributed to improved surgical technique, the increase in surgeons trained in
      laparoscopic procedures, as well increased public awareness with celebrities
      having successfully undergone surgery. The number of surgeons and hospitals
      offering bariatric services is increasing. How then does a surgeon or a hospital
      develop a competitive strategy? The first step is to understand the health-care
      industry. The key forces are rivalry among present competitors, and the
      bargaining power of suppliers and buyers. While bariatric surgery currently is in
      a growth phase, time and competition will force practitioners to compete on the
      basis of price, unless they find true competitive advantage. Value innovation, is
      a means of creating new marketing space by looking across the conventionally
      defined boundaries of business--across substitute industries, across strategic
      groups, across buyer groups, across complementary product and service offerings,
      and across the functional-emotional orientation of an industry. One can compete
      by offering similar services focusing primarily on cost efficiencies as the key
      to profitability. Alternatively, one can break free from the pack by innovating
      and focusing on delivering superior value to the customer. As the market for
      bariatric surgery becomes increasingly overcrowded, profitable growth is not
      sustainable without developing a clear differential advantage in the market.
      Value innovation allows you to develop that advantage.

PMID- 15846453
TI  - Warning! Dangerous curve ahead: the learning curve.

PMID- 15846454
TI  - Uterosacral ligament in postmenopausal women with or without pelvic organ
      prolapse.
AB  - The uterosacral ligaments are thought to contribute to pelvic support. The
      objective of this study was to compare the structural components of these
      ligaments in women with and without pelvic organ prolapse (POP). We characterized
      uterosacral ligaments of 25 postmenopausal women with POP and 16 controls
      histomorphologically and immunohistochemically by quantifying their content of
      collagen I, III, and smooth muscle using a computerized image analysis. In 84%
      the uterosacral ligaments were composed of more than 20% of smooth muscle cells.
      There was no difference in collagen I expression and smooth muscle cell amount
      between women with POP and those without. In contrast, the collagen III
      expression was significantly related to the presence of POP (p<0.001) rather than
      age or parity. Our findings suggest that the higher collagen III expression might
      be a typical characteristic of POP patients' connective tissue. The considerable
      amount of smooth muscle cells in uterosacral ligaments may provide pelvic
      support.

PMID- 15846455
TI  - Tension-free vaginal tape exposure presenting as a recurrent sterile paraurethral
      abscess.
AB  - We report a case of tension-free vaginal tape (TVT) exposure presenting as a
      recurrent sterile paraurethral abscess at 25 months and 40 months following
      successful continence surgery and describe the management of this problem.

PMID- 15846456
TI  - Method validation and measurement of biomarkers in nonclinical and clinical
      samples in drug development: a conference report.
AB  - Biomarkers are increasingly used in drug development to aid scientific and
      clinical decisions regarding the progress of candidate and marketed therapeutics.
      Biomarkers can improve the understanding of diseases as well as therapeutic and
      off-target effects of drugs. Early implementation of biomarker strategies thus
      promises to reduce costs and time-to-market as drugs proceed through increasingly
      costly and complex clinical development programs. The 2003 American Association
      of Pharmaceutical Sciences/Clinical Ligand Assay Society Biomarkers Workshop
      (Salt Lake City, UT, USA, October 24-25, 2003) addressed key issues in biomarker
      research, with an emphasis on the validation and implementation of biochemical
      biomarker assays, covering from preclinical discovery of efficacy and toxicity
      biomarkers through clinical and postmarketing implementation. This summary report
      of the workshop focuses on the major issues discussed during presentations and
      open forums and noted consensus achieved among the participants on topics from
      nomenclature to best practices. For example, it was agreed that because reliable
      and accurate data provide the basis for sound decision making, biomarker assays
      must be validated in a manner that enables the creation of such data. The nature
      of biomarker measurements often precludes direct application of regulatory
      guidelines established for clinical diagnostics or drug bioanalysis, and future
      guidance on biomarker assay validation should therefore be adaptable enough that
      validation criteria do not stifle creative biomarker solutions.

PMID- 15846458
TI  - Micrometer-scale particle sizing by laser diffraction: critical impact of the
      imaginary component of refractive index.
AB  - PURPOSE: This study evaluated the effect of the imaginary component of the
      refractive index on laser diffraction particle size data for pharmaceutical
      samples. METHODS: Excipient particles 1-5 microm in diameter (irregular
      morphology) were measured by laser diffraction. Optical parameters were obtained
      and verified based on comparison of calculated vs. actual particle volume
      fraction. RESULTS: Inappropriate imaginary components of the refractive index can
      lead to inaccurate results, including false peaks in the size distribution. For
      laser diffraction measurements, obtaining appropriate or "effective" imaginary
      components of the refractive index was not always straightforward. When the
      recommended criteria such as the concentration match and the fit of the
      scattering data gave similar results for very different calculated size
      distributions, a supplemental technique, microscopy with image analysis, was used
      to decide between the alternatives. Use of effective optical parameters produced
      a good match between laser diffraction data and microscopy/image analysis data.
      CONCLUSIONS: The imaginary component of the refractive index can have a major
      impact on particle size results calculated from laser diffraction data. When
      performed properly, laser diffraction and microscopy with image analysis can
      yield comparable results.

PMID- 15846457
TI  - In vitro and pharmacophore-based discovery of novel hPEPT1 inhibitors.
AB  - PURPOSE: The human proton-coupled small peptide carrier (hPEPT1) is a low
      affinity, high-capacity transporter with broad substrate specificity. We have
      taken an iterative in vitro and in silico approach to the discovery of molecules
      with hPEPT1 affinity. METHODS: A pharmacophore-based approach was taken to
      identifying hPEPT1 inhibitors. The well-characterized and relatively high
      affinity ligands Gly-Sar, bestatin, and enalapril were used to generate a common
      features (HIPHOP) pharmacophore. This consisted of two hydrophobic features, a
      hydrogen bond donor, acceptor, and a negative ionizable feature. RESULTS: The
      pharmacophore was used to search the Comprehensive Medicinal Chemistry (CMC)
      database of more than 8000 drug-like molecules and retrieved 145 virtual hits
      mapping to the pharmacophore features. The highest scoring compounds within this
      set were selected and tested in a stably transfected CHO-hPepT1 cell model. The
      antidiabetic repaglinide and HMG CoA reductase inhibitor fluvastatin were found
      to inhibit hPEPT1 with sub-millimolar potency (IC(50) 178 +/- 1.0 and 337 +/- 4
      microM, respectively). The pharmacophore was also able to identify known hPEPT1
      substrates and inhibitors in further database mining of more than 500 commonly
      prescribed drugs. CONCLUSIONS: This study demonstrates the potential of combining
      computational and in vitro approaches to determine the affinity of compounds for
      hPEPT1 and, in turn, provides insights into key molecular interactions with this
      transporter.

PMID- 15846459
TI  - Data supplementation: a pharmacokinetic/pharmacodynamic knowledge creation
      approach for characterizing an unexplored region of the response surface.
AB  - PURPOSE: To develop a data supplementation [i.e., a
      pharmacokinetic/pharmacodynamics (PK/PD) knowledge creation] approach for
      generating supplemental data to be used in characterizing a targeted unexplored
      segment of the response surface. METHODS: The procedure for data supplementation
      can be summarized as follows: 1) statement of the objective of data
      supplementation for PK/PD knowledge creation, 2) performance of PK knowledge
      discovery, 3) PK data synthesis for target dose group(s), 4) covariate data
      synthesis for virtual subjects in the target dose group(s), 5) discovery of
      hidden knowledge from real data set to which supplemental data will be added, 6)
      implementation of a data supplementation methodology, and 7) discovery and
      communication of the created knowledge. A nonparametric approximate Bayesian
      multiple supplementation and its modification, structure-based multiple
      supplementation, which is an adaptation of the approximate Bayesian bootstrap, is
      proposed as a method of data supplementation for PK/PD knowledge creation. The
      structured-based multiple supplementation methodology was applied to characterize
      the effect of a target dose of 100 mg that was unexplored in a previously
      concluded study that investigated the effect of 200- and 600-mg doses on
      biomarker response. RESULTS: The target dose of 100 mg was found to produce a
      response comparable with that of the 200 mg and better than that obtained with
      the 600 mg. CONCLUSIONS: Implementation of the PK/PD knowledge creation process
      through data supplementation resulted in gaining knowledge about a targeted
      region of a response surface (i.e., the effect of a target dose) that was not
      previously studied in a completed study without expending resources in conducting
      a new study.

PMID- 15846460
TI  - A population pharmacokinetic model for montelukast disposition in adults and
      children.
AB  - PURPOSE: The purpose was to develop a population pharmacokinetic model for
      montelukast after intravenous administration. Clinical trial simulations were
      conducted using the model developed to identify the lowest intravenous dose in 6-
      to 14-year-old children that would give montelukast systemic exposures that were
      comparable to those found to be associated with efficacy in adults. METHODS: Two
      clinical studies were conducted where montelukast was administered intravenously
      as a 7-mg dose to adults and as a 3.5-mg dose to children aged 6 to 14 years.
      Model development included defining the base pharmacostatistical model and
      investigating the effects of demographic variables [age and total body weight
      (TBW)] on the structural parameters, using a nonlinear mixed effect modeling
      approach. RESULTS: A linear three-compartment pharmacokinetic model was found to
      best describe the disposition of montelukast. Inclusion of TBW as a covariate
      caused a 35% and 63% decrease in the interindividual variabilities on clearance
      and central volume of distribution, respectively. Trial simulations suggested
      that a 5.25-mg intravenous dose of montelukast should be chosen in children aged
      6 to 14 years. CONCLUSIONS: The model developed can adequately describe the
      intravenous pharmacokinetics of montelukast and can be used as a useful tool for
      dose selection in pediatric subpopulations.

PMID- 15846461
TI  - Covariate detection in population pharmacokinetics using partially linear mixed
      effects models.
AB  - PURPOSE: To introduce partially linear mixed effects models (PLMEMs), to
      illustrate their use, and to compare the power and Type I error rate in detecting
      a covariate effect with nonlinear mixed effects modeling using NONMEM. METHODS:
      Sparse concentration-time data from males and females (1:1) were simulated under
      a 1-compartment oral model where clearance was sex-dependent. All possible
      combinations of number of subjects (50, 75, 100, 150, 250), samples per subject
      (2, 4, 6), and clearance multipliers (1 to 1.25) were generated. Data were
      analyzed with and without sex as a covariate using PLMEM (maximum likelihood
      estimation) and NONMEM (first-order conditional estimation). Four covariate
      screening methods were examined: NONMEM using the likelihood ratio test (LRT),
      PLMEM using the LRT, PLMEM using Wald's test, and analysis of variance (ANOVA) of
      the empirical Bayes estimates (EBEs) for CL treating sex as a categorical
      variable. The percent of simulations rejecting the null hypothesis of no
      covariate effect at the 0.05 level was determined. 300 simulations were done to
      calculate power curves and 1000 simulations were done (with no covariate effect)
      to calculate Type I error rate. Actual implementation of PLMEMs is illustrated
      using previously published teicoplanin data. RESULTS: Type I error rates were
      similar between PLMEM and NONMEM using the LRT, but were inflated (as high as
      36%) based on PLMEM using Wald's test. Type I error rate tended to increase as
      the number of observations per subject increased for the LRT methods. Power
      curves were similar between the PLMEM and NONMEM LRT methods and were slightly
      more than the power curve using ANOVA on the EBEs of CL. 80% power was achieved
      with 4 samples per subject and 50 subjects total when the effect size was
      approximately 1.07, 1.07, 1.08, and 1.05 for LRT using PLMEMs, LRT using NONMEM,
      ANOVA on the EBEs, and Wald's test using PLMEMs, respectively. CONCLUSIONS: PLMEM
      and NONMEM covariate screening using the LRT had similar Type I error rates and
      power under the data generating model. PLMEMs offers a viable alternative to
      NONMEM-based covariate screening.

PMID- 15846462
TI  - Transdermal delivery of human growth hormone through RF-microchannels.
AB  - PURPOSE: To evaluate the bioavailability and bioactivity of human growth hormone
      (hGH) delivered transdermally through microchannels (MCs) in the skin created by
      radio-frequency (RF) ablation. METHODS: The creation of MCs was observed in
      magnified rat and guinea pig skin after staining by methylene blue. Various doses
      of hGH in a dry form were applied on rat or guinea pig (GP) skin after the
      formation of MCs. The pharmacokinetic profile of systemic hGH in both animal
      models was monitored for 15 h post patch application. Bioactivity of the
      transdermally delivered hGH was verified by measuring IGF-I levels in
      hypophysectomized rats. RESULTS: The ordered array of MCs was clearly visible in
      the magnified rat and guinea pig skin. The MCs were very uniform in diameter and
      of equal separation. Creation of MCs in the outer layers of the skin enabled
      efficient delivery of hGH, with a bioavailability of 75% (rats) or 33% (GPs)
      relative to subcutaneous (s.c.) injection with plasma profiles resembling that of
      s.c. injection. Elevated levels of systemic insulin-like growth factor-1 (IGF-I)
      were observed after transdermal delivery of hGH to hypophysectomized rats
      indicative of the bioactivity of the transdermally delivered hGH in vivo.
      CONCLUSIONS: Formation of RF-microchannels is a well-controlled process. These
      MCs permitted the transdermal delivery of bioactive hGH in rats and GPs with high
      bioavailability.

PMID- 15846463
TI  - Nipecotic acid: systemic availability and brain delivery after nasal
      administration of nipecotic acid and n-butyl nipecotate to rats.
AB  - PURPOSE: The purpose of this research was to characterize nipecotic acid
      pharmacokinetics in blood and brain after intravenous (i.v.) and nasal
      administration of nipecotic acid and its n-butyl ester. METHODS: Nipecotic acid
      and its n-butyl ester were administered to rats i.v. and intranasally (n = 5
      rats/drug per route), and nipecotic acid pharmacokinetics in blood were
      characterized. Nipecotic acid concentration-time profiles were determined in
      blood by noncompartmental and compartmental methods. Nipecotic acid was also
      dosed i.v. and its n-butyl ester was dosed by nasal and i.v. routes, and brain
      levels of nipecotic acid over the subsequent 4 h (n = 5 rats/time point per
      route) were assessed. RESULTS: The absolute systemic availability of nipecotic
      acid after nasal dosing was 14%. After i.v. and nasal dosing of the n-butyl
      ester, nipecotic acid systemic availability was 97% and 92%, respectively. Both
      i.v. and nasal administration of the n-butyl ester resulted in a significantly
      longer terminal half-life and larger mean resident time and volume of
      distribution for nipecotic acid than was observed after an i.v. nipecotic acid
      dose. Total brain exposure to nipecotic acid was not significantly different
      after nasal and i.v. dosing of the n-butyl ester. However, the brain/blood
      nipecotic acid ratio declined significantly with time after i.v. and nasal dosing
      of the ester prodrug. Nipecotic acid was not detectable in brain after i.v.
      dosing of nipecotic acid. CONCLUSIONS: The use of an ester formulation was
      crucial to delivering nipecotic acid to the brain. Preliminary evidence strongly
      suggests ester hydrolysis is rate limiting to nipecotic acid brain delivery. Once
      nipeoctic acid was formed, it displayed tissue trapping in brain. Parenteral
      dosing of nipecotic acid esters is unnecessary for systemic or brain delivery of
      nipecotic acid and possibly other CNS active zwitterion esters.

PMID- 15846464
TI  - Local delivery of vancomycin for the prophylaxis of prosthetic device-related
      infections.
AB  - PURPOSE: To evaluate the in vivo efficacy and pharmacokinetics of vancomycin
      delivered from glycerylmonostearate (GMS) implants in a prosthetic-device based
      biofilm infection model. METHODS: A biofilm infection model was developed in male
      Sprague-Dawley rats by implanting a vascular graft on the dorsal side of each rat
      and infecting it with 1.5 x 10(8) cfu/ml Staphylococcus epidermidis. The rats
      were divided into 3 groups of 6 rats each: 1) the control group that received no
      antibiotics, 2) the IM group that received multiple IM injections of vancomycin
      at a dose of 25 mg/kg every 6 h for a total of 12 doses, and 3) the implant group
      that received GMS implants designed to deliver vancomycin at a total dose of 300
      mg/kg for a period of 4 days. The pharmacokinetics of vancomycin was determined
      from IM and implant groups by analyzing for vancomycin in blood using HPLC. In
      vivo efficacy was studied by evaluation of the wound site and the prosthetic
      device upon excision, for evidence of infection in the form of purulent discharge
      at the wound site and yellowish discoloration of the prosthetic device and
      inflammation as sign of biofilm formation. Microbiological evaluation on the
      wound site and the prosthetic device was performed by culturing the swabs at the
      wound site and the prosthetic device in sterile tryptic soy broth for 36-48 h at
      37 degrees C. RESULTS: Vancomycin was successfully delivered in a sustained
      manner for 100 h from GMS implants and the resulting plasma profile showed that
      the concentrations, after an initial burst, plateaued at about of 4.77 +/- 1.43
      mug/ml with less fluctuations than the IM group in which the plasma
      concentrations fluctuated between 2.73 +/- 0.94 mug/ml and 19.26 +/- 3.67 mug/ml.
      Upon excision of the wound site, all the animals in the control group developed
      infection in the form of purulent discharge and yellowish discoloration of the
      prosthetic device. However, none of the rats in the implant group showed evidence
      of infection clearly demonstrating the efficacy of the local delivery system in
      preventing infection. Systemically delivered vancomycin by IM injections failed
      to prevent infection in four out of six rats. Microbiological evaluation of the
      wound site and prosthetic device resulted in isolation of biofilm-producing
      organisms such as Staphylococcus epidermidis, Enterococcus faecalis, and
      Staphylococcus aureus. These organisms were isolated in greater number of animals
      in the control group compared to the IM and implant groups. CONCLUSIONS: The GMS
      implants as a delivery system for vancomycin were successful in preventing
      infection in all the animals compared to the IM and control groups demonstrating
      the efficacy of a local delivery system in a prosthetic device related biofilm
      infection model.

PMID- 15846465
TI  - Lyophilized paclitaxel magnetoliposomes as a potential drug delivery system for
      breast carcinoma via parenteral administration: in vitro and in vivo studies.
AB  - PURPOSE: The study reports in vitro and biological evaluation of lyophilized
      negatively charged paclitaxel magnetic liposomes as a potential carrier for
      breast carcinoma via parenteral administration. METHODS: Paclitaxel in
      magnetoliposomes were extracted by centrifugation and quantified by high
      performance liquid chromatography (HPLC). Biological properties were studied
      using pharmacokinetics, in vivo distribution and cytotoxicity assays, as well as
      a mouse model of EMT-6 breast cancer. METHODS: Pharmacokinetic studies showed
      that encapsulation of paclitaxel in magnetoliposomes produced marked difference
      over the drug in Cremophor EL/ethanol pharmacokinetics, with an increased
      t(1/2beta) 19.37 h against 4.11 h. For in vivo distribution, paclitaxel
      concentration of lyophilized magnetoliposomes in the tumor was much higher than
      that of lyophilized conventional liposomes or Cremophor EL/ethanol, whereas in
      heart it was much lower than the latter two formulations via s.c. and i.v.
      administration. Lyophilized paclitaxel magnetic liposomes showed more potency on
      the therapy of breast cancer than other formulations via s.c. and i.p.
      administration. CONCLUSIONS: The current study demonstrates that paclitaxel
      magnetoliposomes can effectively be delivered to tumor and exert a significant
      anticancer activity with fewer side effects in the xenograft model.

PMID- 15846466
TI  - Development and characterization of bioadhesive vaginal films of sodium
      polystyrene sulfonate (PSS), a novel contraceptive antimicrobial agent.
AB  - PURPOSE: Polystyrene sulfonate (PSS) is a novel noncytotoxic antimicrobial
      contraceptive agent. A gel formulation of PSS was found safe for vaginal
      administration in phase I clinical trials. The purpose of the current study was
      to develop and evaluate novel bioadhesive vaginal film formulations of PSS.
      METHODS: PSS films were prepared by solvent evaporation and optimized for various
      physical, mechanical, and aesthetic properties. Further, films were evaluated for
      various biological activities and safety. RESULTS: Vaginal films containing 300
      mg PSS per unit have been developed, using generally regarded as safe (GRAS)
      listed excipients. The films are colorless, transparent, thin, soft, and tough,
      dissolve rapidly in physiologic fluid to form a smooth, viscous and bioadhesive
      solution that could be retained in the vagina for prolonged intervals. Sperm
      function inhibition (hyaluronidase and cervical mucus penetration) and
      antimicrobial activities against human immunodeficiency virus (HIV) and herpes
      simplex virus (HSV) by PSS films were found comparable to PSS. Also, films did
      not inhibit normal vaginal microflora (Lactobacillus) and were noncytotoxic as
      indicated by negligible sperm immobilization and cytotoxicity to host cell
      assays. CONCLUSIONS: Rapidly dissolving bioadhesive vaginal film formulation of
      PSS with desired physical, mechanical, aesthetic, and biological properties is a
      suitable candidate vaginal microbicide for prevention of sexually transmitted
      disease (STDs) and is ready for toxicological and clinical evaluation.

PMID- 15846467
TI  - Pharmacokinetics and tissue retention of (Gd-DTPA)-cystamine copolymers, a
      biodegradable macromolecular magnetic resonance imaging contrast agent.
AB  - PURPOSE: To investigate the pharmacokinetics, long-term tissue retention of
      Gd(III) ions, and magnetic resonance imaging (MRI) contrast enhancement of
      extracellular biodegradable macromolecular Gd(III) complexes, (Gd-DTPA)-cystamine
      copolymers (GDCC), of different molecular weights. METHODS: The pharmacokinetics
      of blood clearance and long-term Gd(III) retention of GDCC were investigated in
      Sprague-Dawley rats. Pharmacokinetic parameters were calculated by using a two
      compartment model. The blood pool contrast enhancement of GDCC was evaluated in
      Sprague-Dawley rats on a Siemens Trio 3T MR scanner. Gd-(DTPA-BMA) was used as a
      control. RESULTS: The alpha phase half-life of Gd-(DTPA-BMA) and GDCC with
      molecular weights of 18,000 (GDCC-18) and 60,000 Da (GDCC-60) was 0.48 +/- 0.16
      min, 1.08 +/- 0.24 min, and 1.74 +/- 0.57 min, and the beta phase half-life was
      21.2 +/- 5.5 min, 26.5 +/- 5.9 min, and 53.7 +/- 15.9 min, respectively. GDCC had
      minimal long-term Gd tissue retention comparable to that of Gd-(DTPA-BMA). GDCC
      resulted in more significant contrast enhancement in the blood pool than Gd-(DTPA
      BMA). CONCLUSIONS: GDCC provides a prolonged blood pool retention time for
      effective MRI contrast enhancement and then clears rapidly with minimal
      accumulation of Gd (III) ions. It is promising for further development as a blood
      pool MRI contrast agent.

PMID- 15846468
TI  - Pharmacodynamic assessment of the benztropine analogues AHN-1055 and AHN-2005
      using intracerebral microdialysis to evaluate brain dopamine levels and
      pharmacokinetic/pharmacodynamic modeling.
AB  - PURPOSE: The benztropine (BZT) analogues bind with high affinity to the dopamine
      transporter (DAT) and demonstrate a behavioral and pharmacokinetic profile unlike
      that of cocaine. The development of a predictive pharmacokinetic/pharmacodynamic
      (PK/PD) model to characterize the concentration-effect relationship between the
      BZT analogues and brain dopamine (DA) levels is an important step in the
      evaluation of these compounds as potential cocaine abuse pharmacotherapies.
      Hence, the objective of this study was to mathematically characterize the PD of
      BZT analogues and cocaine, using appropriate PK/PD models. METHODS: Dialysis
      probes were stereotaxically implanted into the nucleus accumbens of Sprague
      Dawley rats (275-300 g). Extracellular fluid (ECF) DA levels were measured after
      intravenous administration of the BZT analogues AHN-1055 and AHN-2005, as well as
      cocaine using high performance liquid chromatography-electrochemical detection
      (HPLC-ECD). PD models were used to describe the relationship between the BZT
      analogues or cocaine and brain microdialysate DA, and suitability was based on
      standard goodness-of-fit criteria. RESULTS: The BZT analogues produced a
      sustained increase in brain microdialysate DA levels in comparison to cocaine.
      The time of maximum concentration (T(max)) for brain microdialysate DA was 2 h
      for AHN-1055 and 1 h for AHN-2005 compared to a T(max) of 10 min for cocaine. The
      duration of brain microdialysate DA elevation was approximately 12-24 h for the
      BZTs in comparison to 1 h for cocaine. An indirect model with inhibition of loss
      of response and a sigmoid E(max) model best described the PK/PD for the BZT
      analogues and cocaine, respectively. The 50% of maximum inhibition (IC(50)) of
      the loss of DA was lower for AHN-2005 (226 +/- 27.5 ng/ml) compared to AHN-1055
      (321 +/- 19.7 ng/ml). In addition, the EC(50) for cocaine was 215 +/- 11.2 ng/ml.
      CONCLUSIONS: The slow onset and long duration of BZT analogue-induced DA
      elevation may avoid the reinforcing effects and craving of cocaine. Further, the
      developed models will be useful in characterizing the PK/PD of other analogues
      and aid in the assessment of the therapeutic efficacy of the BZT analogues as
      substitute medications for cocaine abuse.

PMID- 15846469
TI  - Lack of improvement of oral absorption of ME3277 by prodrug formation is ascribed
      to the intestinal efflux mediated by breast cancer resistant protein
      (BCRP/ABCG2).
AB  - PURPOSE: ME3229, an ester-type prodrug of a hydrophilic glycoprotein IIb/IIIa
      antagonist (ME3277), failed to show improved oral absorption. Okudaira et al. (J.
      Pharmacol. Exp. Ther. 294. 580-587, 2000) provided a piece of evidence that this
      is ascribed to an efflux system, distinct from P-gp and MRP2, that extrudes
      ME3277 formed from ME3229 in the intestinal epithelial cells. The aim of the
      present study is to examine the involvement of breast cancer resistant protein
      (BCRP/ABCG2) as a cause of low oral absorption of ME3229. METHODS: The transport
      activity of ME3277 in the presence and absence of ATP was determined using a
      rapid filtration method with the membrane vesicles prepared from LLC-PK1 cells
      expressing BCRP. The plasma concentrations of ME3229 and its metabolites were
      compared between Bcrp1(-/-) mice and wild-type mice after a single-pass perfusion
      of small intestine with ME3229. RESULTS: The ATP-dependent uptake of ME3277 was
      greater in BCRP-expressing membrane vesicles than that in the control vesicles.
      Furthermore, it was found that after intestinal perfusion with ME3229 for 60 min,
      the plasma concentrations of ME3277 and PM-5, a metabolite of ME3229, increased 2
      fold and 3-fold, respectively, in Bcrp1 knockout mice. It is possible that BCRP
      acts synergistically with intestinal carboxylesterases. CONCLUSION: These results
      suggest that Bcrp1 plays an important role in the intestinal efflux of ME3277
      and, probably, PM-10 and PM-11, metabolites of ME3229, and limits its BA after
      oral administration of ME3229.

PMID- 15846470
TI  - Differential contributions of rOat1 (Slc22a6) and rOat3 (Slc22a8) to the in vivo
      renal uptake of uremic toxins in rats.
AB  - PURPOSE: Evidence suggests that uremic toxins such as hippurate (HA),
      indoleacetate (IA), indoxyl sulfate (IS), and 3-carboxy-4-methyl-5-propyl-2
      furanpropionate (CMPF) promote the progression of renal failure by damaging
      tubular cells via rat organic anion transporter 1 (rOat1) and rOat3 on the
      basolateral membrane of the proximal tubules. The purpose of the current study is
      to evaluate the in vivo transport mechanism responsible for their renal uptake.
      METHODS: We investigated the uremic toxins transport mechanism using the
      abdominal aorta injection technique [i.e., kidney uptake index (KUI) method],
      assuming minimal mixing of the bolus with serum protein from circulating serum.
      RESULTS: Maximum mixing was estimated to be 5.8% of rat serum by measuring
      estrone sulfate extraction after addition of 0-90% rat serum to the arterial
      injection solution. Saturable renal uptake of p-aminohippurate (PAH, K(m) = 408
      microM) and benzylpenicillin (PCG, K(m) = 346 microM) was observed, respectively.
      The uptake of PAH and PCG was inhibited in a dose-dependent manner by unlabeled
      PCG (IC(50) = 47.3 mM) and PAH (IC(50) = 512 microM), respectively, suggesting
      that different transporters are responsible for their uptake. A number of uremic
      toxins inhibited the renal uptake of PAH and PCG. Excess PAH, which could inhibit
      rOat1 and rOat3, completely inhibited the saturable uptake of IA, IS, and CMPF by
      the kidney, and by 85% for HA uptake. PCG inhibited the total saturable uptake of
      HA, IA, IS, and CMPF by 10%, 10%, 45%, and 65%, respectively, at the
      concentration selective for rOat3. CONCLUSIONS: rOat1 could be the primary
      mediator of the renal uptake of HA and IA, accounting for approximately 75% and
      90% of their transport, respectively. rOat1 and rOat3 contributed equally to the
      renal uptake of IS. rOat3 could account for about 65% of the uptake of CMPF under
      in vivo physiologic conditions. These results suggest that rOat1 and rOat3 play
      an important role in the renal uptake of uremic toxins and the induction of their
      nephrotoxicity.

PMID- 15846471
TI  - Investigation of solubility and dissolution of a free base and two different salt
      forms as a function of pH.
AB  - PURPOSE: To evaluate the effect of pH on solubility and dissolution rates of a
      model weak base, haloperidol, and two different salt forms, hydrochloride and
      mesylate. METHODS: pH-solubility profiles were determined by using haloperidol
      base, haloperidol hydrochloride, and haloperidol mesylate as starting materials;
      concentrated or diluted HCl or NaOH solutions were added to aqueous suspensions
      of solids to adjust pH to desired values. Intrinsic dissolution rates were
      determined using intrinsic dissolution apparatus under various pH-stat
      conditions. Further, approximation of diffusion layer pH was estimated from that
      of 10% w/w slurries of drug substances in dissolution media, which were used to
      correlate with intrinsic dissolution rates of haloperidol and its salt forms
      under different pHs. RESULTS: pH-solubility profiles of haloperidol base and its
      HCl salt were similar, while when the mesylate salt was used as starting
      material, it exhibited a higher solubility between pH 2 and 5. The higher
      solubility of the mesylate salt at pH 2-5 is attributed to its higher solubility
      product (K(sp)) than that of the hydrochloride salt. The pH-solubility profiles
      indicated a pH(max) (pH of maximum solubility) of approximately 5, indicating
      that the free base would exist as the solid phase above this pH and a salt would
      be formed below this pH. Below pH 1.5, all solubilities were comparable due to a
      conversion of haloperidol base or the mesylate salt to the HCl salt form when HCl
      was used as the acidifying agent. These were confirmed by monitoring the solid
      phase by differential scanning calorimeter. When their dissolution rates are
      tested, dissolution rates of the mesylate salt were much higher than those of the
      free base or the HCl salt, except at very low pH (<2). Dissolution rates of free
      base and HCl salt also differed from each other, where that of HCl salt exhibits
      higher dissolution rates at higher pHs. A direct correlation of dissolution rate
      with solubility at diffusion layer pH at the surface of dissolving solid was
      established for haloperidol, its hydrochloride, and mesylate salts. CONCLUSIONS:
      Using pH-solubility and pH-dissolution rate interrelationships, it has been
      established that diffusion layer pH could be used to explain the observed rank
      order in dissolution rates for different salt forms. A non-hydrochloride salt,
      such as a mesylate salt, may provide advantages over a hydrochloride salt due to
      its high solubility and lack of common ion effect unless at very low pH.

PMID- 15846472
TI  - A natural compound (ginsenoside Re) isolated from Panax ginseng as a novel
      angiogenic agent for tissue regeneration.
AB  - PURPOSE: The primary challenge for tissue engineering is to develop a vascular
      supply that can support the metabolic needs of the engineered tissues in an
      extracellular matrix. In this study, the feasibility of using a natural compound,
      ginsenoside Re, isolated from Panax ginseng in stimulating angiogenesis and for
      tissue regeneration was evaluated. METHODS: Effects of ginsenoside Re on the
      proliferation, migration, and tube formation of human umbilical vein endothelial
      cells (HUVECs) were examined in vitro. Additionally, angiogenesis and tissue
      regeneration in a genipin-fixed porous acellular bovine pericardium
      (extracellular matrix; ECM) incorporated with ginsenoside Re implanted
      subcutaneously in a rat model were investigated. Basic fibroblast growth factor
      (bFGF) was used as a control. RESULTS: It was found that HUVEC proliferation,
      migration in a Transwell plate, and tube formation on Matrigel were all
      significantly enhanced in the presence of bFGF or ginsenoside Re. Additionally,
      effects of ginsenoside Re on HUVEC proliferation, migration, and tube formation
      were dose-dependent and reached a maximal level at a concentration of about 30
      microg/ml. The in vivo results obtained at 1 week postoperatively showed that the
      density of neocapillaries and the tissue hemoglobin content in the ECMs were
      significantly enhanced by bFGF or ginsenoside Re. These results indicated that
      angiogenesis in the ECMs was significantly enhanced by loading with bFGF or
      ginsenoside Re. At 1 month postoperatively, vascularzied neo-connective-tissue
      fibrils were found to fill the pores in the ECMs loaded with bFGF or ginsenoside
      Re. CONCLUSIONS: The aforementioned results indicated that like bFGF, ginsenoside
      Re-associated induction of angiogenesis enhanced tissue regeneration, supporting
      the concept of therapeutic angiogenesis in tissue-engineering strategies.

PMID- 15846473
TI  - Molecular cloning and functional analyses of OAT1 and OAT3 from cynomolgus monkey
      kidney.
AB  - PURPOSE: The functional characterization of monkey OAT1 (SLC22A6) and OAT3
      (SLC22A8) was carried out to elucidate species differences in the OAT1- and OAT3
      mediated transport between monkey and human. METHODS: The cDNAs of monkey OAT1
      and OAT3 were isolated from monkey kidney, and their stable transfectants were
      established in HEK293 cells (mkOAT1- and mkOAT3-HEK). Transport studies were
      performed using cDNA transfectants, and kinetic parameters were compared among
      rat, monkey and human. RESULTS: The amino acid sequences of mkOAT1 and mkOAT3
      exhibit 97% and 96% identity to their corresponding human orthologues. For OAT1,
      there was no obvious species difference in the K(m) values and the relative
      transport activities of 11 substrates with regard to p-aminohippurate transport.
      For OAT3, there was no species difference in the K(m) values and in the relative
      transport activities of nine substrates with regard to benzylpenicillin transport
      between monkey and human. However, the relative transport activities of indoxyl
      sulfate, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, and estrone-3-sulfate
      showed a difference between primates and rat and gave a poor correlation.
      CONCLUSIONS: These results suggest that monkey is a good predictor of the renal
      uptake of organic anions in the human.

PMID- 15846474
TI  - Treatment of hyperbilirubinemia in Eisai hyperbilirubinemic rat by transfecting
      human MRP2/ABCC2 gene.
AB  - PURPOSE: Multidrug resistance-associated protein 2 (MRP2/ABCC2) is predominantly
      expressed in the liver canalicular membrane and plays an important role in the
      biliary excretion of organic anions including glucuronide and glutathione
      conjugates. The purpose of this study is to construct a new evaluation system for
      human MRP2 by expressing human MRP2 in Eisai hyperbilirubinemic rat (EHBR) liver,
      the rat Mrp2 function of which is hereditarily defective. METHODS: In order to
      express human MRP2 in liver, we used the Tet-off adenovirus expression system.
      After 72 h infection, we evaluated the protein expression and localization in the
      liver and the transport activity of [(3)H]E(2)17ssG and [(3)H]DNP-SG by preparing
      canalicular membrane vesicles (CMVs). We also evaluated the biliary excretion and
      plasma concentration of DBSP after bolus administration and the plasma
      concentration of endogenous direct and indirect bilirubin. RESULTS: The
      localization of human MRP2 in EHBR liver was found to be at the bile canalicular
      membrane. Clear ATP-dependent uptake of [(3)H]E(2)17ssG and [(3)H]DNP-SG into
      CMVs was observed by using the CMVs prepared from the liver where human MRP2 was
      transfected. Furthermore, the blood to bile clearance of DBSP increased
      approximately 3-fold after expression of human MRP2. In addition, the plasma
      direct bilirubin level in EHBR was reduced by the expression of human MRP2.
      CONCLUSIONS: These results suggest that this evaluation system for human MRP2 may
      be useful for evaluating the function of human MRP2.

PMID- 15846475
TI  - High-performance frontal analysis of the binding of thyroxine enantiomers to
      human serum albumin.
AB  - PURPOSE: The aim of this study was to characterize the binding property between
      thyroxine and human serum albumin (HSA) qualitatively and enantioselectively
      using high-performance frontal analysis (HPFA). METHODS: An on-line HPLC system
      consisting of an HPFA column, an extraction column, and an analytical HPLC column
      was developed to be used to determine the unbound concentrations of thyroxine
      enantiomers. RESULTS: Both enantiomers were bound to human serum albumin at two
      high-affinity sites with similar affinities. The binding constant (K) and the
      number of binding sites on an HSA molecule (n) evaluated from Scatchard plot
      analysis were K = 1.01 x 10(6)m(-1) and n = 1.90 for L: -thyroxine, and K = 9.71
      x 10(5) m(-1) and n = 1.97 for D: -thyroxine. The binding sites were identified
      using phenylbutazone and diazepam as site-specific probes for sites I and II,
      respectively, and each enantiomer was found to bind to both sites. Incorporation
      of a chiral HPLC column into the on-line system permitted the investigation of
      enantiomer-enantiomer interactions, which revealed that both enantiomers
      competitively bind to the same binding sites without significant allosteric
      effects.

PMID- 15846476
TI  - Development of novel nonaqueous ethylcellulose gel matrices: rheological and
      mechanical characterization.
AB  - PURPOSE: This study reports the rheological and mechanical characterization of
      novel non-aqueous ethylcellulose gel matrices intended for topical drug delivery.
      An attempt was also made to explain the molecular interaction within the gel
      systems from a molecular conformational approach. METHODS: Nonaqueous gel
      matrices were prepared from three fine particle grades of ethylcellulose and
      propylene glycol dicaprylate/dicaprate. Continuous and oscillatory shear
      rheometry was performed using a cone-and-plate rheometer and mechanical
      characterization was performed using a universal tensile tester. RESULTS: The gel
      matrices exhibited prominent viscoelastic behaviour, yield stress and thixotropy.
      Rheological and mechanical properties showed significant upward trends with
      increased polymeric chain length and polymer concentrations. Good linear
      correlations were obtained between rheological and mechanical properties. The
      solvent molecular conformation was found to play a role in affecting the
      formation of gel networks via intermolecular hydrogen bonding between
      ethylcellulose polymer chains. CONCLUSIONS: Ethylcellulose was successfully
      formulated as a nonaqueous gel with propylene glycol dicaprylate/dicaprate. The
      novel nonaqueous gel exhibited rheological profiles corresponding to a physically
      cross-linked three dimensional gel network, with suitable mechanical
      characteristics for use as a vehicle for topical drug delivery. Molecular
      conformation of the solvent was found to influence the molecular interactions
      associated with formation of ethylcellulose gel networks.

PMID- 15846478
TI  - [Primary and secondary osteoporosis. The important role of internal medicine in
      its differential diagnosis].
AB  - Bone metabolism as an important part of internal medicine is covered by
      endocrinologists, rheumatologists and nephrologists. Primary osteoporosis is an
      inheritable metabolic bone disease, which can be strongly modified by lifestyle,
      ageing and underlying diseases. Chronic inflammatory diseases, disorders of
      metabolism and nutritional deficits enhance the risk. Secondary osteoporosis is
      caused by endocrinological disorders and drugs such as glucocorticoids. It is the
      task of internists to clinically recognise and diagnose prominent individual risk
      factors for primary osteoporosis and underlying diseases for secondary
      osteoporosis. The key competence of internal medicine in metabolism, hormone
      related disorders, malignant diseases and in handling complex medical treatment
      modalities represents an indispensable segment of an interdisciplinary network
      approach in patient care, research and teaching. This network includes
      orthopaedic surgery, paediatrics and gynaecology in addition to other
      specialties.

PMID- 15846479
TI  - Candidate gene database and transcript map for peach, a model species for fruit
      trees.
AB  - Peach (Prunus persica) is a model species for the Rosaceae, which includes a
      number of economically important fruit tree species. To develop an extensive
      Prunus expressed sequence tag (EST) database for identifying and cloning the
      genes important to fruit and tree development, we generated 9,984 high-quality
      ESTs from a peach cDNA library of developing fruit mesocarp. After assembly and
      annotation, a putative peach unigene set consisting of 3,842 ESTs was defined.
      Gene ontology (GO) classification was assigned based on the annotation of the
      single "best hit" match against the Swiss-Prot database. No significant homology
      could be found in the GenBank nr databases for 24.3% of the sequences. Using core
      markers from the general Prunus genetic map, we anchored bacterial artificial
      chromosome (BAC) clones on the genetic map, thereby providing a framework for the
      construction of a physical and transcript map. A transcript map was developed by
      hybridizing 1,236 ESTs from the putative peach unigene set and an additional 68
      peach cDNA clones against the peach BAC library. Hybridizing ESTs to genetically
      anchored BACs immediately localized 11.2% of the ESTs on the genetic map. ESTs
      showed a clustering of expressed genes in defined regions of the linkage groups.
      [The data were built into a regularly updated Genome Database for Rosaceae (GDR),
      available at (http://www.genome.clemson.edu/gdr/).].

PMID- 15846480
TI  - Intensive Care Medicine: what we offer to our readers and what the readers think
      of it.

PMID- 15846481
TI  - Are somatosensory evoked potentials the best predictor of outcome after severe
      brain injury? A systematic review.
AB  - OBJECTIVE: Many tests have been used to predict outcome following severe brain
      injury. We compared predictive powers of clinical examination (pupillary
      responses, motor responses and Glasgow Coma Scale, GCS), electroencephalography
      (EEG) and computed tomography (CT) to that of somatosensory evoked potentials
      (SEPs) in a systematic review. MATERIALS AND METHODS: Medline (1976-2002) and
      Embase (1980-2002) were searched, manual review of article reference lists was
      conducted, and authors were contacted. We selected 25 studies addressing the
      prediction of outcome after severe brain injury using SEPs and either GCS, EEG,
      CT, pupillary or motor responses. Outcomes were determined for patients with
      normal or bilaterally absent SEPs and graded measures of GCS, EEG, CT, pupillary
      responses or motor responses. For favourable outcome prediction SEPs were
      superior in sensitivity, specificity and positive and negative predictive values,
      except for pupillary responses which had superior sensitivity and GCS which had
      higher specificity. SEPs had superior summary receiver operating characteristic
      curves, with the exception of motor responses, and superior ratio of odds ratios.
      For unfavourable outcome prediction SEPs were superior to the other tests in
      sensitivity, specificity and positive and negative predictive values, except for
      motor and pupillary responses, GCS and CTs which had superior sensitivity. All
      SEP summary receiver operating characteristic curves and pooled ratio of odds
      ratios were superior. CONCLUSIONS: Although imperfect, SEPs appear to be the best
      single overall predictor of outcome. There is sufficient evidence for clinicians
      to use SEPs in the prediction of outcome after brain injury.

PMID- 15846482
TI  - 5-HT6 receptor antagonists improve performance in an attentional set shifting
      task in rats.
AB  - RATIONALE AND OBJECTIVE: Performance on the Wisconsin Card Sorting Test (WCST),
      which requires patients to 'shift attention' between stimulus dimensions (sorting
      categories), is impaired in diseases such as schizophrenia. The rat attentional
      set shifting task is an analogue of the WCST. Given that 5-HT(6) receptor
      antagonists improve cognitive performance and influence cortical neurochemistry
      in rats, the present study investigated the effects of 5-HT(6) receptor
      antagonists upon attentional set shifting in rats. METHODS: Rats were tested in
      this paradigm following sub-chronic SB-399885-T or SB-271046-A (both 10 mg kg(-1)
      bid, p.o. for 8 days prior to testing and either 4 or 2 h prior to testing on day
      9, respectively). Rats were trained to dig in baited bowls for a food reward and
      to discriminate based on odour or digging media (Habituation, day 8). In a single
      session (day 9), rats performed a series of discriminations, including reversals
      (REV), intra-dimensional (ID) and extra-dimensional (ED) shifts. RESULTS: Neither
      compound altered performance during Habituation. On the test day, both SB-399885
      T and SB-271046-A reduced the total trials to reach criterion and the total
      errors made when data were collapsed across all discriminations (P<0.05-0.01).
      Further, both compounds significantly reduced the trials to criterion for REV-1
      (P<0.05-0.01) and abolished the ID/ED shift. SB-399885-T, but not SB-271046-A,
      reduced trials required to complete the ED shift (P<0.05) and the number of
      errors made during completion of the ID (P<0.05) and ED shifts (P<0.01).
      CONCLUSION: 5-HT(6) receptor antagonists improved performance in the attentional
      set shifting task and may have therapeutic potential in the treatment of
      disorders where cognitive deficits are a feature, including schizophrenia.

PMID- 15846483
TI  - Utility of contrast-enhanced 3D turbo-flash MR angiography in evaluating the
      intracranial venous system.
AB  - The objective of this study was to compare the effectiveness of contrast-enhanced
      3D turbo-flash and 2D time-of-flight (TOF) magnetic resonance angiography (MRA)
      sequences in the visualization and evaluation of the intracranial venous system.
      A prospective study was carried out on 41 patients referred to our Magnetic
      Resonance Imaging (MRI) unit with clinical findings suggestive of dural sinus
      thrombosis. Contrast-enhanced 3D turbo-flash and 2D TOF MRA sequences were
      performed, and the dural sinuses and cerebral veins were classified into five
      grades according to the quality of visualization and presence of thrombosis. We
      found the dural sinuses and cerebral veins to be normal in all sequences in 31
      patients. Thrombosis of dural sinuses was detected in ten patients, with four of
      these ten cases found only in the contrast-enhanced 3D turbo-flash sequence. In
      general, complete visualization of cerebral veins and dural sinuses was
      significantly better accomplished with contrast-enhanced 3D turbo-flash MRA than
      with 2D TOF in either coronal or sagittal/oblique planes. Although 2D TOF MRA may
      be superior in detecting chronic dural sinus thrombosis, contrast-enhanced 3D
      turbo-flash MRA sequences may offer advantages for the early diagnosis and
      management of acute and subacute dural sinus thrombosis.

PMID- 15846484
TI  - Poly(3-hydroxyalkanoate) polymerase synthesis and in vitro activity in
      recombinant Escherichia coli and Pseudomonas putida.
AB  - We tested the synthesis and in vitro activity of the poly(3-hydroxyalkanoate)
      (PHA) polymerase 1 from Pseudomonas putida GPo1 in both P. putida GPp104 and
      Escherichia coli JMU193. The polymerase encoding gene phaC1 was expressed using
      the inducible PalkB promoter. It was found that the production of polymerase
      could be modulated over a wide range of protein levels by varying inducer
      concentrations. The optimal inducer dicyclopropylketone concentrations for PHA
      production were at 0.03% (v/v) for P. putida and 0.005% (v/v) for E. coli. Under
      these concentrations the maximal polymerase level synthesized in the E. coli host
      (6% of total protein) was about three- to fourfold less than that in P. putida
      (20%), whereas the maximal level of PHA synthesized in the E. coli host (8% of
      total cell dry weight) was about fourfold less than that in P. putida (30%). In
      P. putida, the highest specific activity of polymerase was found in the mid
      exponential growth phase with a maximum of 40 U/g polymerase, whereas in E. coli,
      the maximal specific polymerase activity was found in the early stationary growth
      phase (2 U/g polymerase). Our results suggest that optimal functioning of the PHA
      polymerase requires factors or a molecular environment that is available in P.
      putida but not in E. coli.

PMID- 15846485
TI  - Medium optimization by response surface methodology for poly-gamma-glutamic acid
      production using dairy manure as the basis of a solid substrate.
AB  - Dairy manure, supplemented with agro-industrial materials, was used as the solid
      substrate for high yield of poly-gamma-glutamic acid (gamma-PGA) by Bacillus
      subtilis CCTCC202048. The solid-state fermentation medium was optimized by
      response surface methodology. In the first optimization step, a Plackett-Burman
      design was used to evaluate the influence of related factors. Wheat bran, soybean
      cake and glutamic acid were found to be more compatible supplement with dairy
      manure and positively influenced on gamma-PGA production. In the second step, the
      concentrations of the three supplemental nutrients above were further optimized
      using a Box-Behnken design. The average gamma-PGA yield (4.70%) in triplicate
      under optimal conditions was obtained on the laboratory scale, whereas it was
      3.58% at compost experiment. These would lay a foundation for lessening the
      pollution of dairy manure, increasing fertilizer efficiency and exploring a late
      model organic fertilizer that retains water and nutrients.

PMID- 15846486
TI  - Diagnosis of urinoma complicating a renal graft using 99mTc-DTPA scintigraphy and
      factor analysis.

PMID- 15846487
TI  - Clinical evaluation of 2D versus 3D whole-body PET image quality using a
      dedicated BGO PET scanner.
AB  - PURPOSE: Three-dimensional positron emission tomography (3D PET) results in
      higher system sensitivity, with an associated increase in the detection of
      scatter and random coincidences. The objective of this work was to compare, from
      a clinical perspective, 3D and two-dimensional (2D) acquisitions in terms of
      whole-body (WB) PET image quality with a dedicated BGO PET system. METHODS: 2D
      and 3D WB emission acquisitions were carried out in 70 patients. Variable
      acquisition parameters in terms of time of emission acquisition per axial field
      of view (aFOV) and slice overlap between sequential aFOVs were used during the 3D
      acquisitions. 3D and 2D images were reconstructed using FORE+WLS and OSEM
      respectively. Scatter correction was performed by convolution subtraction and a
      model-based scatter correction in 2D and 3D respectively. All WB images were
      attenuation corrected using segmented transmission scans. Images were blindly
      assessed by three observers for the presence of artefacts, confidence in lesion
      detection and overall image quality using a scoring system. RESULTS:
      Statistically significant differences between 2D and 3D image quality were only
      obtained for 3D emission acquisitions of 3 min. No statistically significant
      differences were observed for image artefacts or lesion detectability scores.
      Image quality correlated significantly with patient weight for both modes of
      operation. Finally, no differences were seen in image artefact scores for the
      different axial slice overlaps considered, suggesting the use of five slice
      overlaps in 3D WB acquisitions. CONCLUSION: 3D WB imaging using a dedicated BGO
      based PET scanner offers similar image quality to that obtained in 2D considering
      similar overall times of acquisitions.

PMID- 15846488
TI  - Fusion imaging using a hybrid SPECT-CT camera improves port perfusion
      scintigraphy for control of hepatic arterial infusion of chemotherapy in
      colorectal cancer patients.
AB  - PURPOSE: Exclusive and homogeneous perfusion of the liver is considered essential
      for the efficacy of hepatic arterial infusion of chemotherapy (HAI). The aim of
      this study was to evaluate port perfusion scintigraphy in colorectal cancer
      patients using a hybrid SPECT-CT system for control of minimally invasive intra
      arterial port systems within the scope of a phase II trial. METHODS: In 24
      consecutive patients, the perfusion territories of intra-arterial hepatic port
      systems were assessed by port scintigraphy with( 99m)Tc-labelled macroaggregated
      albumin employing planar imaging, SPECT and SPECT-CT (acquired with a hybrid
      SPECT-CT camera). The results of blinded reading of the scintigraphic modalities
      concerning the intra- and extrahepatic perfusion pattern were compared with
      combined image analysis (angiography and contrast-enhanced dedicated CT) and
      patient history for validation. RESULTS: Extrahepatic perfusion was correctly
      seen in three patients, while suspected extrahepatic perfusion could be excluded
      in one. In 46 liver lobes, perfusion patterns were correctly visualised by SPECT
      CT in 100% of cases (planar, 67%; SPECT, 86%). Assessing the perfusion pattern
      inside the liver on a segmental basis (segments, n=138), SPECT-CT revealed
      correct segmental assignment of tracer distribution in 100% and was significantly
      superior to SPECT alone (accuracy, 84%; p<0.001). The scintigraphic findings
      resulted in changes in therapeutic management in 8/24 patients (33%); in two of
      these the relevant findings were visualised only by SPECT-CT. CONCLUSION: In
      patients receiving HAI, port perfusion scintigraphy by fusion imaging with a
      hybrid SPECT-CT system provides important information for therapy optimisation
      and appears to be superior to SPECT alone.

PMID- 15846489
TI  - Tumor-derived interleukin (IL)-6 induced anti-tumor effect in immune-compromised
      hosts.
AB  - Tumor-derived cytokines, such as interleukin (IL)-6, function in the context of
      tumor-to-host interactions, and their functions in immune-compromised hosts need
      to be addressed in the light of ever- increasing number of patients under
      immunosuppression. We studied the effects, in immune-comprised animals, of tumor
      derived IL-6 on tumor growth using an experimental tumor vaccination model.
      Murine mammary carcinoma FM3A clone 25 (CL25) cells, which neither produce IL-6
      nor express IL-6 receptors, were used. cDNA for murine IL-6 (mIL-6) was
      introduced to the CL25 cells, resulting in a high-producer (mIL-6H) clone. In the
      severe combined immune-deficient (SCID) mice, the inoculation 3 weeks earlier of
      mIL-6H to a dorsal flank site suppressed the growth of the CL25 cells at the
      opposite flank site; a tumor-derived IL-6-mediated vaccination effect occurred.
      In the T-cell-deficient nude mice, the inoculations 4 weeks earlier of mIL-6H
      suppressed the growth of CL25, but the simultaneous inoculation of these
      transfectants did not affect the growth of CL25. Reducing the number of
      inoculated transfectants or a shorter vaccination period obscured the suppressive
      effect. The amounts of circulating tumor-reactive immunoglobulin did not
      correlate with the suppressive effect. The subcutaneous injection of the anti
      CD40 antibody generated a further suppression of tumor growth in the mIL-6H
      inoculated, but not in the mock-inoculated, T-cell-deficient mice. In the immune
      competent hosts, a suppressive effect was not observed. Natural killer (NK)
      activity was augmented in the spleen of mIL-6H-inoculated scid mice. This study
      indicated a possible vaccination effect with tumor-derived IL-6 in immune
      compromised hosts.

PMID- 15846490
TI  - A DeImmunized chimeric anti-C3b/iC3b monoclonal antibody enhances rituximab
      mediated killing in NHL and CLL cells via complement activation.
AB  - Complement-dependent cytotoxicity (CDC) is a key mechanism of Rituximab (RTX)
      action in killing non-Hodgkin's lymphoma (NHL) cells both in vitro and probably
      in vivo. A DeImmunized, mouse/human chimeric monoclonal antibody (Mab), H17,
      specific for cell-associated complement C3 cleavage products, C3b and iC3b, was
      generated to enhance RTX-mediated killing of target cells by CDC. When NHL cell
      lines were treated with RTX and H17 in the presence of complement for 1 h, there
      was 40-70% more cell death than that observed with RTX alone. The enhancing
      effect of H17 was also seen over longer treatment periods. H17 was tested ex vivo
      against primary cells from NHL and chronic lymphocytic leukemia (CLL) patients.
      In RTX-resistant NHL samples, H17 enhanced RTX-mediated killing; in the remaining
      samples RTX + complement alone promoted more than 80% killing, and no significant
      enhancement was observed. The H17 antibody also increased RTX-mediated killing in
      four out of nine CLL samples. H17 may have therapeutic applications in NHL and
      CLL treatment as an adjunctive therapy to RTX. It might also enhance the activity
      of other therapeutic antibodies that work through CDC.

PMID- 15846491
TI  - Liposome-polycation-DNA (LPD) particle as a carrier and adjuvant for protein
      based vaccines: therapeutic effect against cervical cancer.
AB  - With the successful identification of many tumor-specific antigens, tumor
      associated antigens, and the potential of using unfractioned tumor cell
      derivatives as tumor antigens, a system and/or adjuvant that can deliver these
      antigens and help them to induce strong and effective anti-tumor immune responses
      is greatly needed. Previously, we reported that a MHC class I-restricted peptide
      epitope derived from human papillomavirus (HPV) 16 E7 protein, when incorporated
      into a clinically proven safe LPD (liposome-polycation-DNA) particle, was able to
      effectively eradicate tumors established in mice. Cervical cancer is the second
      most common cancer among women worldwide. HPV infection is clearly linked to this
      cancer. Vaccines based on the early (E) gene products of HPV could be effective
      in controlling it. However, besides the fact that epitope vaccines have many
      limitations particularly, concerning the diverse HLAs in humans, the use of the
      epitope as an antigen prevented us from fully characterizing the immune responses
      induced by the LPD as a vaccine carrier and/or adjuvant in previous studies. In
      the present study, by using the HPV 16 E7 protein as an antigen, we first showed
      that LPD, as a vaccine carrier and adjuvant induced strong and robust immune
      responses, both cellular and antibody. We then showed that immunization with LPD
      particles incorporated with either the wild type HPV 16 E7 protein or a
      potentially safer mutant induced strong immune responses that caused complete
      regressions of a model cervical cancer tumor established in murines. LPD could be
      a potent vaccine carrier and/or adjuvant for many antigens.

PMID- 15846492
TI  - CTLA-4 blockade augments human T lymphocyte-mediated suppression of lung tumor
      xenografts in SCID mice.
AB  - Previous studies by others using transplantable murine tumor models have
      demonstrated that the administration of antibodies that block CTLA-4 interaction
      with B7 can provoke the elimination of established tumors, and that the tumor
      suppression is mediated by T-cells and/or cells expressing NK1.1. Studies from
      our lab have established in a human/severe combined immunodeficient (SCID) mouse
      chimeric model that autologous peripheral blood leukocytes (PBL) can suppress the
      growth of tumor xenografts in a PBL dose-dependent fashion, and that this
      suppression is dependent upon the patient's T and NK cells. Using this
      human/mouse chimeric model, we sought to determine whether an antibody blockade
      of CTLA-4 would enhance the anti-tumor response of a patient's PBL. It was first
      important to determine whether the tumor suppression observed in the SCID model
      was dependent upon CD28/B7 co-stimulation. Blockade of B7 with a human CTLA-4-Ig
      fusion protein completely abrogated the lymphocyte-mediated tumor suppression,
      confirming in this model that tumor suppression is dependent upon a CD28/B7 co
      stimulation. Using two different CTLA-4 specific monoclonal antibodies, we
      observed that CTLA-4 blockade significantly enhanced the human lymphocyte
      mediated tumor suppression in mice co-engrafted with PBL and tumor cells. This
      enhancement was observed in both an allogeneic setting (in which the PBL were
      allogeneic with respect to the tumor) and an autologous setting (in which the PBL
      and tumor were from the same patient). These results sustain the notion that
      human anti-tumor immune response can be augmented (in vivo) by blocking the
      interaction between CTLA-4 and B7.

PMID- 15846493
TI  - Magnetic resonance imaging of tropical ulcers.

PMID- 15846494
TI  - Analysis of the human brain in primary progressive multiple sclerosis with
      mapping of the spatial distributions using 1H MR spectroscopy and diffusion
      tensor imaging.
AB  - Primary progressive multiple sclerosis (ppMS; n=4) patients and controls (n=4)
      were examined by 1H magnetic resonance spectroscopy (MRS) and diffusion tensor
      imaging (DTI) in order to map choline (Cho), creatine and N-acetylaspartate
      (NAA), the fractional anisotropy (FA) and the apparent diffusion constant (ADC).
      After chemical shift imaging (point-resolved spectroscopy, repetition time/echo
      time 1,500 ms/135 ms) of a supraventricular volume of interest of 8x8x2 cm3 (64
      voxels) MRS peak areas were matched to the results of DTI for the corresponding
      volume elements. Mean FA and NAA values were reduced in the ppMS patients
      (P<0.01, both) and the ADC increased (P<0.02). The spatial distribution of NAA
      showed strong correlation to ADC in both ppMS patients and controls (r =-0.74 and
      r= -0.70; P<0.00001, both), and weaker correlations to FA (r=0.49 and r=0.41;
      P<0.00001, all). FA and ADC also correlated significantly with Cho in patients
      and controls (P<0.00001, all). The relationship of Cho and NAA to the ADC and the
      FA and thus to the content of neuronal structures suggests that these metabolite
      signals essentially originate from axons (NAA) and the myelin sheath (Cho). This
      is of interest in view of previous reports in which Cho increases were associated
      with demyelination and the subsequent breakdown of neurons.

PMID- 15846495
TI  - Functional MRI activation of somatosensory and motor cortices in a hand-grafted
      patient with early clinical sensorimotor recovery.
AB  - The aim of this study was to investigate somatosensory and motor cortical
      activity with functional MRI (fMRI) in a hand-grafted patient with early clinical
      recovery. The patient had motor fMRI examinations before transplantation, and
      motor and passive tactile stimulations after surgery. His normal hand and a
      normal group were studied for comparison. A patient with complete brachial plexus
      palsy was studied to assess the lack of a fMRI signal in somatosensory areas in
      the case of total axonal disconnection. Stimulating the grafted hand revealed
      significant activation in the contralateral somatosensory cortical areas in all
      fMRI examinations. The activation was seen as early as 10 days after surgery;
      this effect cannot be explained by the known physiological mechanisms of nerve
      regeneration. Although an imagination effect cannot be excluded, the objective
      clinical recovery of sensory function led us to formulate the hypothesis that a
      connection to the somatosensory cortex was rapidly established. Additional cases
      and fundamental studies are needed to assess this hypothesis, but several
      observations were compatible with this explanation. Before surgery, imaginary
      motion of the amputated hand produced less intense responses than executed
      movements of the intact hand, whereas the normal activation pattern for right
      handed subjects was found after surgery, in agreement with the good clinical
      motor recovery.

PMID- 15846496
TI  - Subtypes of peripheral adenocarcinoma of the lung: differentiation by thin
      section CT.
AB  - The purpose of this study was to scrutinize morphological characteristics of thin
      section CT of the histopathological subtypes of adenocarcinoma of the lung. The
      subjects consisted of 83 patients with 87 adenocarcinomas measuring 3 cm or less
      in the largest. The tumors were divided into three groups (group I: Noguchi's
      histological subtypes type A and B tumors, group II: type C tumors, and group
      III: type D, E, and F tumors). In each group, tumor size, shape (round versus
      polygonal), presence of air bronchogram, bubble-like areas, coarse spiculation,
      pleural tag, and ratio of ground glass attenuation (GGA) were evaluated. Most of
      the group II lesions showed polygonal shape, whereas tumors in other groups were
      round in shape (P<0.01). Air bronchogram and bubble-like areas of low attenuation
      was seen more frequently in group II compared with those in group III (P<0.01).
      GGA areas were largest in group I and smallest in group III (P<0.01). We believe
      thin-section CT findings reflect the histopathological subtypes of adenocarcinoma
      of the lung. The presence of air bronchogram and bubble-like areas of low
      attenuation areas in particular is useful to differentiate replacement growth
      tumors from non-replacement growth tumors.

PMID- 15846497
TI  - Comparison of capsule endoscopy and magnetic resonance (MR) enteroclysis in
      suspected small bowel disease.
AB  - BACKGROUND AND AIMS: Small bowel MR enteroclysis and wireless capsule endoscopy
      (WCE) are new diagnostic tools for the investigation of the small bowel. The aim
      of this study was to compare the diagnostic yield of WCE with MR enteroclysis in
      the detection of small bowel pathologies. METHODS: A total of 36 patients were
      included in the study. Indications for imaging of the small bowel were proven or
      suspected small bowel Crohn's disease (CD; n=18), obscure gastrointestinal (GI)
      bleeding (n=14) and tumour surveillance (n=4). RESULTS: In patients with Crohn's
      disease WCE detected significantly more inflammatory lesions in the first two
      segments of the small bowel compared with MR enteroclysis (12 patients vs. 1
      patient, p=0.016). In 5 out of 14 (36%) patients with GI bleeding, angiodysplasia
      was detected as a possible bleeding source. Three of these patients had active
      bleeding sites detected by WCE. One patient had scattered inflammation of the
      mucosa. MR enteroclysis did not reveal any intestinal abnormalities in this
      patient group. MR enteroclysis provided extraintestinal pathologies in 10 out of
      36 (28%) patients. CONCLUSION: In patients with Crohn's disease WCE revealed
      significantly more inflammatory lesions in the proximal and middle part of the
      small bowel in comparison to MR enteroclysis, whereas in patients with obscure GI
      bleeding WCE was superior to MR enteroclysis.

PMID- 15846498
TI  - Voiding and sexual dysfunction after deep rectal resection and total mesorectal
      excision: prospective study on 52 patients.
AB  - OBJECTIVE: Voiding and sexual dysfunction after deep rectal resection have been
      described with various frequencies in the literature. In this study, we
      prospectively evaluated the baseline preoperative voiding and sexual function in
      a cohort of patients undergoing deep rectal resection with mesorectal excision to
      determine any pre-existing abnormalities. Postoperatively, we sought first to
      determine the frequency of a urinary or sexual dysfunction, secondly whether
      there is a time-dependent change of a dysfunction and thirdly whether there is a
      relationship between postoperative urological dysfunction and the patient's age.
      PATIENTS AND METHODS: Fifty-two patients (36 men and 16 women) with a primary
      rectal carcinoma were prospectively examined directly before and after the
      operation, as well after the third and sixth postoperative month. The
      preoperative urological evaluation consisted of a careful voiding and sexual
      history, uroflowmetry and a sonographic residual urine determination. A detailed
      sexual history was obtained via the use of a questionnaire. RESULTS: Urological
      dysfunction: Preoperatively, 49 of the 52 patients had a completely normal
      bladder function and three patients had post void residual >100 ml.
      Postoperatively, 12 of the 49 patients with normal preoperatively urinary
      function had voiding dysfunction, but only four male patients had residual urine
      in the third postoperative month. Therefore, in about 90% of the patients,
      postoperative bladder function became normal and only 10% suffered from vesical
      denervation after 6 months. We could not determine a relationship between the
      degree of bladder dysfunction and the patient's age due to a relatively small
      patient cohort in this study. Sexual dysfunction: Preoperatively, 36 (seven
      women, 29 men) of the 52 patients were potent and had regular sexual intercourse.
      Eleven men specified a limited erection, but all had occasional sexual
      intercourse. One of the potent men experienced no ejaculation. Postoperatively,
      eight of the 29 men were impotent and two of the 29 men experienced retrograde
      ejaculation. Therefore, 30% of the preoperatively potent men had sexual
      dysfunction postoperatively. There was no correlation between the postoperative
      impotence and the age of the patients at the time of surgery. Although it is
      likely that the potency may diminish with advanced age, the incidence of
      impotence was not higher in the older patients of our study. CONCLUSIONS: The
      results of our study underline the importance of risk estimation for possible
      postoperative urological dysfunction by means of preoperative urologic evaluation
      in this patient collective. Of patients with postoperative bladder dysfunction,
      90% improved within 6 months after surgery and only 10% continued to have bladder
      dysfunction beyond 6 months, indicating irreversible nerve damage.

PMID- 15846499
TI  - Fas/CD95 signaling rather than angiogenesis or proliferative activity is a useful
      prognostic factor in patients with resected liver metastases from colorectal
      cancer.
AB  - BACKGROUND: The selection of resective therapy for colorectal hepatic metastases
      remains controversial. The aim of this study is to investigate the prognostic
      factors for patients with resected liver metastases from colorectal cancer by
      analyzing not only clinicopathological factors but also recent immunohistological
      markers. METHODS: Eighty-five patients underwent hepatic resection for metastatic
      colorectal cancer over the past 20 years. Fas/CD95 expression, microvessel
      density, and proliferating cell nuclear antigen (PCNA) proliferative activity
      were assessed with immunohistochemical methods in addition to the
      clinicopathological factors. Survival analysis was performed using the Kaplan
      Meier method and Cox proportional hazards model, both univariately and
      multivariately. RESULTS: Univariate and multivariate analyses revealed that the
      number of metastases, Fas/CD95 expression, and postoperative carcinoembryonic
      antigen doubling time (CEADT) were significant prognostic indicators, whereas the
      mode of hepatic resection, chemotherapy, and other clinicopathological factors
      had no influence on survival. Fas/CD95 index correlated with postoperative CEADT
      (p=0.039), number of metastases (p=0.018), and survival (p=0.023). CONCLUSIONS:
      Our study confirmed the number of metastases and CEADT as prominent prognostic
      factors after hepatic resection for metastatic colorectal cancer. These two
      factors reflect the degree of Fas/CD95 signaling rather than angiogenesis or
      cancer growth rate.

PMID- 15846500
TI  - Cancer mortality among municipal pest-control workers.
AB  - OBJECTIVES: This epidemiological study was carried out in order to investigate
      the hypothesis of a relationship between cancer occurrence and occupational
      exposure in a population of municipal pest-control workers exposed to a wide
      range of pesticides and other chemicals. METHODS: The study was designed as a
      mortality historical cohort study. The cohort comprised all subjects ever
      employed in a municipal pest-control service between 1979 and 1994. The follow-up
      period lasted from 1979 to 2000. The mortality rates of pest-control workers were
      compared with those of a regional population. A job exposure matrix was
      developed, which took into account four types of chemicals: formaldehyde,
      ethylene oxide, insecticides and rodenticides. RESULTS: None of the 181 subjects
      of the cohort, leading to 3,107 person-years, was lost to follow-up. Thirty-nine
      of them died, and all the causes of deaths were ascertained. The standardized
      mortality ratios (SMRs) for all causes of deaths and for all cancer causes were
      significantly greater than unity: 1.61 (1.14-2.20) and 2.24 (1.39-3.43),
      respectively. Non-significant excesses were observed for most cancer sites,
      except for lung cancer, which had a low SMR. We obtained significant excesses for
      cancer in workers with more than 20 years of employment [SMR = 2.42 (1.43-3.82)].
      Cancer mortality tended to increase insignificantly with formaldehyde and
      rodenticides exposures, whereas no clear patterns were observed for ethylene
      oxide and insecticides. However, significant excesses were observed for the
      highest exposure levels of formaldehyde, insecticides and rodenticides.
      CONCLUSIONS: This study showed a statistically significant excess of cancer
      mortality in a population of municipal pest-control workers exposed to a wide
      variety of chemicals. These cancer sites might be related to occupational
      activities, since they tended to be more frequently observed when duration of
      employment increased.

PMID- 15846501
TI  - A new unusual low molecular weight carbohydrate in the red algal genus
      Hypoglossum (Delesseriaceae, Ceramiales) and its possible function as an
      osmolyte.
AB  - The low molecular weight carbohydrates in various species of the red algal genus
      Hypoglossum (Delesseriaceae, Ceramiales) were analysed using HPLC, 1H and 13C
      nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry.
      All specimens contained the heteroside digeneaside which is considered as
      chemosystematic marker for the Ceramiales. A new HPLC method was developed for
      the separation and quantification of this compound, and concentrations between
      131.6 mmol kg(-1) and 539.6 mmol kg(-1) DW could be measured among the species
      tested. In addition, during the HPLC analysis another new low molecular weight
      carbohydrate was detected in two species from The Philippines (H. barbatum) and
      Western Australia (H . heterocystideum), and its chemical structure elucidated as
      digalactosylglycerol applying various NMR experiments. The remaining Hypoglossum
      taxa lack this compound. Although digalactosylglycerol occurred in high
      concentrations in the range of 221.7 and 438.7 mmol kg(-1) DW in H. barbatum and
      H . heterocystideum, respectively, it has never been reported for any other algal
      species before. Therefore, to test the possible physiological function of this
      unusual carbohydrate as organic osmolyte, H. barbatum was treated with a range of
      salinities. While the digeneaside content remained almost unchanged, the
      digalactosylglycerol concentration strongly increased with increasing salinities
      from 70 mmol kg(-1) DW at 20 psu to 215 mmol kg(-1) DW at 45 psu. In conclusion,
      while neither published work nor the present study indicate digeneaside to play
      more than a minor role in osmotic acclimation, the data presented strongly
      support an osmotic function of digalactosylglyerol.

PMID- 15846502
TI  - Enzymic transfer of alpha-L-arabinopyranosyl residues to exogenous 1,4-linked
      beta-D-galacto-oligosaccharides using solubilized mung bean (Vigna radiata)
      hypocotyl microsomes and UDP-beta-L-arabinopyranose.
AB  - A single alpha-L-arabinopyranosyl (alpha-L-Arap) residue was shown, by a
      combination of chemical and spectroscopic methods, to be transferred to O-4 of
      the nonreducing terminal galactosyl (Gal) residue of 2-aminobenzamide (2AB)
      labeled galacto-oligosaccharides when these oligosaccharides were reacted with
      UDP-ss-L-arabinopyranose (UDP-ss-L-Arap) in the presence of a Triton X-100
      soluble extract of microsomal membranes isolated from mung bean (Vigna radiata,
      L. Wilezek) hypocotyls. Maximum-(1-->4)-arabinopyranosyltransferase activity was
      obtained at pH 6.0-6.5 and 20 degrees C in the presence of 25 mM Mn2+. The enzyme
      had an apparent K m of 45 microM for the 2AB-labeled galactoheptasaccharide and
      330 microM for UDP-ss-L-Arap. A series of 2AB-labeled galacto-oligosaccharides
      with a degree of polymerization (DP) between 6 and 10 that contained a single
      alpha-L-Arap residue linked to the former nonreducing terminal Gal residue were
      generated when the 2AB-labeled galactohexasaccharide (Gal6-2AB) was reacted with
      UDP- ss-L-Ara p in the presence of UDP-beta-D-Galp and the solubilized microsomal
      fraction. The mono-arabinosylated galacto-oligosaccharides are not acceptor
      substrates for the galactosyltransferase activities known to be present in mung
      bean microsomes. These results show that mung bean hypocotyl microsomes contain
      an enzyme that catalyzes the transfer of Arap to the nonreducing Gal residue of
      galacto-oligosaccharides and suggest that the presence of a alpha-L-Arap residue
      on the former terminal Gal residue prevents galactosylation of galacto
      oligosaccharides.

PMID- 15846503
TI  - Simultaneous observation of collagen and elastin in normal and pathological
      tissues: analysis of Sirius-red-stained sections by fluorescence microscopy.
AB  - In order to observe collagen and elastic fibers simultaneously, sections of human
      aorta, skin, lung, liver, and bladder were stained by Sirius red and analyzed by
      fluorescence microscopy. In all cases, the fibers of collagen presented the
      characteristic fluorescent red-orange color that results from the interaction of
      this extracellular protein with the dye, whereas elastic fibers showed strong
      green fluorescence (intrinsic fluorescence). This method efficiently detects
      collagen and elastic fibers when these two structures are present and could have
      valuable applications in processes that involves both fibers.

PMID- 15846504
TI  - Sequence of protein expression of bone sialoprotein and osteopontin at the
      developing interface between repair cementum and dentin in human deciduous teeth.
AB  - Experimental periodontal regeneration studies have revealed the weak binding of
      repair cementum to the root surface, whereas attachment of cementum to dentin
      preconditioned by odontoclasts appears to be superior. The aim of this study has
      been, therefore, to analyze the structural and partial biochemical nature of the
      interface that develops between resorbed dentin and repair cementum by using
      human deciduous teeth as a model. Aldehyde-fixed and decalcified tooth samples
      were embedded in acrylic or epoxy resins and sectioned for light and transmission
      electron microscopy. Antibodies against bone sialoprotein (BSP) and osteopontin
      (OPN), two noncollagenous proteins accumulating at hard tissue interfaces in bone
      and teeth, were used for protein A-gold immunocytochemistry. Light microscopy
      revealed a gradually increasing staining intensity of the external dentin matrix
      starting after the withdrawal of the odontoclast. Labeling for both BSP and OPN
      was first detected among the exposed collagen fibrils and in the intratubular
      dentin matrix when odontoclasts had withdrawn but mesenchymal cells were present.
      Subsequently, collagen fibrils of the repair cementum were deposited
      concomitantly with the appearance of labeling for BSP and OPN over the
      intratubular, intertubular, and peritubular dentin matrix. Labeled mineralization
      foci indicated the advancing mineralization front, and the collagenous repair
      matrix became integrated in an electron-dense organic material that showed
      labeling for BSP and OPN. Thus, no distinct planar interfacial matrix layer lies
      between the resorbed dentin and the repair cementum. The results suggest that
      odontoclasts precondition the dentin matrix such that the repair cementum becomes
      firmly attached.

PMID- 15846505
TI  - Localization of type 5 17beta-hydroxysteroid dehydrogenase mRNA in mouse tissues
      as studied by in situ hybridization.
AB  - The mouse enzyme type 5 17beta-hydroxysteroid dehydrogenase (17beta-HSD)
      catalyzes the conversion of androstenedione to testosterone and, to a lesser
      degree, the conversion of estrone to estradiol. In order to determine the exact
      sites of action of type 5 17beta-HSD, we studied the cellular localization of the
      mRNA of the enzyme in mouse tissues by using in situ hybridization. Specific
      hybridization signal was found in the liver, ovary, adrenal cortex, and kidney.
      In the liver of mice of both sexes, a strong signal was observed in all
      hepatocytes. In the ovary, specific labeling was detected in the granulosa and
      theca interna cells in growing follicles and in luteal cells. In the female
      adrenal cortex, intense labeling was restricted to the zona reticularis, whereas
      no type 5 17beta-HSD mRNA expression could be found in the male adrenal cortex.
      In the kidney of mice of both sexes, type 5 17beta-HSD mRNA was expressed in
      epithelial cells in both the proximal and distal convoluted tubules. The data
      indicate that androgens and estrogens are formed via the action of type 5 17beta
      HSD in specific cell types in the liver, ovary, adrenal cortex, and kidney.

PMID- 15846506
TI  - Silencing TNFalpha activity by using Remicade or Enbrel blocks inflammation in
      whole muscle grafts: an in vivo bioassay to assess the efficacy of anti-cytokine
      drugs in mice.
AB  - Dramatic clinical success in the treatment of chronic inflammatory diseases has
      resulted from the use of anti-cytokine therapies including specific blocking
      antibodies, soluble receptors and traps to silence the actions of inflammatory
      cytokines such as tumour necrosis factor alpha (TNFalpha) and interleukin-1 (IL
      1). Two agents used clinically to block the functional activity of TNFalpha
      protein are Remicade (an antibody) and Enbrel (a soluble TNF receptor). These
      tools are now being extended to many other clinical disorders. We have a specific
      interest in the treatment of muscle diseases. In order to study the effects of
      novel anti-cytokine drugs on mouse models of human disease, such drugs must be
      investigated to determine whether they are indeed effective in blocking the
      inflammatory response in mouse. This has been carried out by means of a simple in
      vivo bioassay. Histological examination of transverse sections from whole muscle
      autografts in C57BL/10ScSn mice sampled at 5 days after transplantation provides
      an excellent assay model and clearly shows that Remicade and Enbrel block the
      acute inflammatory cell response in vivo. This graft model has also been used to
      show that a single intraperitoneal injection of Remicade (10 microg/g) is long
      lived and effective when administered at 1 week and even 4 weeks prior to the
      assay. Enbrel is highly effective when injected twice at -3 days and -1 day (2 x
      100 microg) before muscle grafting but shows no inhibition of the inflammatory
      response after a single injection (100 microg) 1 week prior to grafting. This
      striking ablation of inflammation by pharmacological blockage of TNFalpha is in
      marked contrast to the lack of any effect in TNFalpha null mice. This simple
      reproducible in vivo assay model in mice can be used to evaluate the efficacy of
      many novel anti-cytokine interventions designed to block inflammation.

PMID- 15846507
TI  - Glucocorticoid programming of adult disease.
AB  - Fetal exposure to elevated levels of glucocorticoids can occur naturally when
      maternal glucocorticoids are elevated in times of stress or when exogenous
      glucocorticoids are administered. Epidemiological studies and animal models have
      shown that, whereas short-term benefits may be associated with fetal
      glucocorticoid exposure, long-term deleterious effects may arise. This review
      compares the effects of exposure to natural versus synthetic glucocorticoids and
      considers the ways in which the timing of the exposure and the sex of the fetus
      may influence outcomes. Some of the long-term effects of glucocorticoid exposure
      may be explained by epigenetic mechanisms.

PMID- 15846508
TI  - Nutritional programming of adult disease.
AB  - Intrauterine and early neonatal life is a period of physiological plasticity,
      during which environmental influences may produce long-term effects. Both
      undernutrition and overnutrition during this period have been shown to change
      disease risk in adulthood. These effects are influenced by the type, timing and
      duration of inappropriate nutrition and by the previous nutritional environment
      and may not be reflected in changes in body size. An understanding of the
      interaction between nutrient imbalance and alteration of gene expression is
      likely to be the key to optimising future health outcomes.

PMID- 15846509
TI  - Pigment epithelium-derived factor (PEDF) blocks angiotensin II signaling in
      endothelial cells via suppression of NADPH oxidase: a novel anti-oxidative
      mechanism of PEDF.
AB  - Angiotensin II (Ang II), the dominant effector of the renin-angiotensin system,
      regulates numerous inflammatory-proliferative responses in vascular wall cells
      and is thus involved in atherosclerosis. We have previously shown that pigment
      epithelium-derived factor (PEDF) inhibits advanced glycation end-product-induced
      pericyte apoptosis, thereby exerting beneficial effects on diabetic retinopathy.
      However, a role for PEDF in vascular inflammation and atherosclerosis remains to
      be elucidated. In this study, we have examined whether PEDF inhibits the Ang-II
      induced endothelial cell (EC) activation in vitro and the way that it might
      achieve this effect. Ang II significantly induced redox-sensitive transcriptional
      factor NF-kappaB activation and subsequent monocyte chemoattractant protein-1
      expression in human umbilical vein ECs (HUVEC), both of which were completely
      inhibited by PEDF or the anti-oxidant N-acetylcysteine. PEDF or diphenylene
      iodonium, an inhibitor of NADPH oxidase, inhibited Ang-II-induced intracellular
      reactive oxygen species (ROS) generation in HUVEC. Furthermore, PEDF inhibited
      Ang-II-induced up-regulation of mRNA levels of p22phox, Nox4, and gp91phox/Nox2,
      which are membrane components of NADPH oxidase, and its enzymatic activity in
      HUVEC. Antisense, but not sense, DNAs against p22phox, Nox4, or gp91phox/Nox2
      were found significantly to inhibit Ang-II-induced ROS generation in HUVEC. These
      results demonstrate that PEDF inhibits Ang-II-induced EC activation by
      suppressing NADPH-oxidase-mediated ROS generation and that PEDF may play a
      protective role in the development and progression of atherosclerosis.

PMID- 15846510
TI  - Rat reduced-folate carrier-1 is localized basolaterally in MDCK kidney epithelial
      cells and contributes to the secretory transport of methotrexate and
      fluoresceinated methotrexate.
AB  - The reduced-folate carrier (Rfc-1), previously also called methotrexate carrier-1
      (MTX-1), was recently identified as accounting for approximately 30% of the
      methotrexate (Mtx) uptake into rat kidney slices. The localization of the carrier
      and its contribution to secretory or reabsorptive flux of the drug was therefore
      evaluated in polarized epithelial layers of Madin Darby canine kidney (MDCK)
      cells. Confocal laser scanning microscopy revealed that the HA-epitope-tagged
      protein was sorted to the basolateral side. In flux assays, the basolateral-to
      apical transport of fluoresceinated methotrexate (FMTX) was two-fold higher than
      in the apical-to-basolateral direction across rat Rfc-1 transfected, but not mock
      transfected, monolayers. The same observation was made for unlabeled Mtx. This
      secretory transport of FMTX was inhibited by an excess of 1 mM Mtx and was
      saturable and temperature-dependent. No differences in directional flux were
      observed for the pure fluorescein label. Removal of sodium resulted in a marked
      decrease of directional FMTX flux. The pH profile of the active transport
      component showed a trough around 6.5 and a maximum at acidic pH, as reported for
      uptake into Rfc-1-expressing cells. Thus, rat Rfc-1 is sorted to the basolateral
      side in polarized MDCK epithelial cells and mediates the secretion of Mtx,
      probably in co-operation with efflux proteins, such as multidrug resistance
      associated proteins, which are also expressed in these cells.

PMID- 15846511
TI  - Inhibition of connexin 43 alters Shh and Bmp-2 expression patterns in embryonic
      mouse tongue.
AB  - The morphogenesis of fungiform papillae occurs in a stereotyped pattern on the
      dorsal surface of the mammalian tongue via epithelial-mesenchymal interactions.
      These interactions are thought to be achieved via intercellular communication.
      Gap junctions can be observed in many developing tissues and have been suggested
      to participate in a variety of functions, including the regulation of cell
      proliferation, differentiation, and apoptosis. Here, we demonstrate that the
      expression of Connexin 43 (Cx43), a gap junction protein, is correlated
      significantly with the development of fungiform papillae, which exhibit a pattern
      formation and morphogenesis similar to the development of other epithelial
      appendages. Antisense-oligodeoxynucleotide (AS-ODN) against Cx43 was used to
      assess the developmental functions of Cx43. The expression patterns of the
      signaling molecules were disrupted by Cx43 inhibition. Interestingly, the
      expression patterns of Shh, a key molecule in the determination of the spacing
      patterns of fungiform papillae, were disturbed after treatment with Cx43 AS-ODN.
      We have also attempted to determine the functions of Bmp-2 by applying NOGGIN
      protein to tongue cultures. Our results indicate that upstream regulation via
      Cx43 controls the Shh and Bmp-2 pathways for the morphogenesis and pattern
      formation of fungiform papillae.

PMID- 15846512
TI  - Developmental expression of MNAR mRNA in the mouse brain.
AB  - During the development of the central nervous system, estrogen influences
      cellular differentiation and determines the functional connectivity of distinct
      neural networks. Estrogens generally act through nuclear estrogen receptors
      (ERs). Recent research has additionally revealed rapid estrogen effects requiring
      the binding of estrogen to membrane/cytoplasmic ERs and the activation of
      intracellular signaling systems such as the Src/MAPK cascade. The scaffold
      protein MNAR/PELP1 appears to be the designated functional mediator of such non
      genomic estrogen effects between non-nuclear ERs and Src/MAPKs. In this study, we
      demonstrate the expression and differential regulation of MNAR mRNA in the
      developing male and female mouse brain by quantitative polymerase chain reaction.
      In the midbrain and hypothalamus, a gradual decline in MNAR mRNA levels has been
      observed prenatally with the highest values at embryonic day 15 and lowest at
      postnatal day 15. In the cortex, mRNA levels do not fluctuate until postnatal day
      7 but decrease thereafter. No differences in MNAR expression between sexes have
      been detected. Analysis of neuronal and astroglia-enriched cell cultures has
      revealed the presence of MNAR in both cell types.

PMID- 15846513
TI  - Breakdown of the blood-brain barrier to proteins in white matter of the
      developing brain following systemic inflammation.
AB  - Compromised blood-brain barrier permeability resulting from systemic inflammation
      has been implicated as a possible cause of brain damage in fetuses and newborns
      and may underlie white matter damage later in life. Rats at postnatal day (P) 0,
      P8 and P20 and opossums (Monodelphis domestica) at P15, P20, P35, P50 and P60 and
      adults of both species were injected intraperitoneally with 0.2-10 mg/kg body
      weight of 055:B5 lipopolysaccharide. An acute-phase response occurred in all
      animals. A change in the permeability of the blood-brain barrier to plasma
      proteins during a restricted period of postnatal development in both species was
      determined immunocytochemically by the presence of proteins surrounding cerebral
      blood vessels and in brain parenchyma. Blood vessels in white matter, but not
      grey matter, became transiently permeable to proteins between 10 and 24 h after
      lipopolysaccharide injection in P0 and P8 rats and P35-P60 opossums. Brains of
      Monodelphis younger than P35, rats older than P20 and adults of both species were
      not affected. Permeability of the blood-cerebrospinal fluid (CSF) barrier to
      proteins was not affected by systemic inflammation for at least 48 h after
      intraperitoneal injection of lipopolysaccharide. These results show that there is
      a restricted period in brain development when the blood-brain barrier, but not
      the blood-CSF barrier, to proteins is susceptible to systemic inflammation; this
      does not appear to be attributable to barrier "immaturity" but to its stage of
      development and only occurs in white matter.

PMID- 15846514
TI  - Genomic and gene expression signature of the pre-invasive testicular carcinoma in
      situ.
AB  - Testicular cancer is the most common malignancy among men in the reproductive age
      and the incidence is increasing, probably caused by environmental factors. Most
      testicular cancers are testicular germ cell tumours and all originate from a
      carcinoma in situ (CIS) pattern. In this review, we focus on the pre-invasive CIS
      and its possible fetal origin by reviewing recent data originating from DNA
      microarrays and comparative genomic hybridisations. A comparison of gene
      expression and genomic aberrations reveal chromosomal "hot spots" with mutual
      clustering of gene expression and genomic amplification. Some of the genes found
      in the hot spots may be involved in creating the CIS phenotype. On the other
      hand, many genes that are highly expressed in CIS are not present in the hot-spot
      areas. The gene expression profile of CIS thus most likely reflects the combined
      result of genomic amplification and increased transcriptional activation and/or
      deficiency in the epigenetic silencing of specific loci. Amplification of
      chromosome 12p, appears to be a good genomic marker of the transition from the
      pre-malignant to malignant CIS cell; this is consistent with recent findings of
      propagation advantages in cultured undifferentiated embryonic stem cells after
      spontaneous amplification in similar regions. The gene expression profile of CIS
      cells has remarkable similarity to that of embryonic stem cells and supports our
      long-standing hypothesis of an early developmental origin of CIS and testicular
      germ cell cancer.

PMID- 15846515
TI  - A primary culture of parotid acinar cells retaining capacity for agonists-induced
      amylase secretion and generation of new secretory granules.
AB  - Exocrine acinar cells, like parotid cells, have difficulty in maintaining their
      functions in cell lines or in primary cultures. For this reason, molecular
      studies on exocrine cell functions are unsatisfactory. To examine the mechanisms
      whereby the functions of parotid acinar cells are maintained, we attempted to
      establish a system for primary culture and transfection of exogenous genes.
      Acinar cells were dispersed from rat parotid glands by digestion with enzymes and
      were cultured in a medium containing rat serum. Most of the cultured cells had
      secretory granules that contained amylase, suggesting that they were derived from
      acinar cells, although they spread on the dish surface and formed filopodia. The
      cultured cells retained both granules and the ability to release amylase in
      response to beta-adrenergic and cholinergic agonists, even 48 h after dispersion.
      However, the total amount of amylase in the cells decreased rapidly from 24 to 48
      h after dispersion. These results suggested that amylase synthesis was more
      damaged than the machinery for exocytosis during culture in vitro. VAMP2 gene
      fused with enhanced green fluorescence protein was transfected into the dispersed
      acinar cells, and VAMP2 protein was expressed and localized to amylase-containing
      granules, as normally seen for endogenous VAMP2 protein. This indicated that new
      granules were generated, and that protein sorting was functional. The cells
      cultured by this method maintained their functions for at least 48 h. They can be
      used for examining the effects of exogenous genes on parotid acinar cell
      functions, such as regulated exocytosis and the maturation of secretory granules.

PMID- 15846516
TI  - Synthesis of transthyretin by the ependymal cells of the subcommissural organ.
AB  - Transthyretin (TTR) is a protein involved in the transport of thyroid hormones in
      blood and cerebrospinal fluid (CSF). The only known source of brain-produced TTR
      is the choroid plexus. In the present investigation, we have identified the
      subcommissural organ (SCO) as a new source of brain TTR. The SCO is an ependymal
      gland that secretes glycoproteins into the CSF, where they aggregate to form
      Reissner's fibre (RF). Evidence exists that the SCO also secretes proteins that
      remain soluble in the CSF. To investigate the CSF-soluble compounds secreted by
      the SCO further, antibodies were raised against polypeptides partially purified
      from fetal bovine CSF. One of these antibodies (against a 14-kDa compound)
      reacted with secretory granules in cells of fetal and adult bovine SCO, organ
      cultured bovine SCO and the choroid plexus of several mammalian species but not
      with RF. Western blot analyses with this antibody revealed two polypeptides of 14
      kDa and 40 kDa in the bovine SCO, in the conditioned medium of SCO explants, and
      in fetal and adult bovine CSF. Since the monomeric and tetrameric forms of TTR
      migrate as bands of 14 kDa and 40 kDa by SDS-polyacrylamide gel electrophoresis,
      a commercial preparation of human TTR was run, with both bands being reactive
      with this antibody. Bovine SCO was also shown to synthesise mRNA encoding TTR
      under in vivo and in vitro conditions. We conclude that the SCO synthesises TTR
      and secretes it into the CSF. Colocalisation studies demonstrated that the SCO
      possessed two populations of secretory cells, one secreting both RF glycoproteins
      and TTR and the other secreting only the former. TTR was also detected in the SCO
      of bovine embryos suggesting that this ependymal gland is an important source of
      TTR during brain development.

PMID- 15846517
TI  - Imaging analysis of mineralocorticoid receptor and importins in single living
      cells by using GFP color variants.
AB  - Mineralocorticoid receptor (MR) is a ligand-dependent transcription factor
      involved in gene regulation in association with another corticosteroid receptor,
      glucocorticoid receptor. In the absence of ligand, MR resides both in the
      cytoplasm and in the nucleus. Agonists increase the number of MRs residing in the
      nucleus. Importins are docking proteins for karyopherin-mediated binding of
      substrate in a nuclear import pathway. To investigate the interactions between MR
      and importins, we analyzed the subcellular distribution of MR and importins in
      response to ligand in living COS-1 cells, which do not express endogenous MR, by
      using fusion proteins labeled with different spectral variants of green
      fluorescent protein. In the cells coexpressing fluorescent protein-tagged (FP)-MR
      and FP-importin alpha, the proteins simultaneously moved into the nucleus from
      the cytoplasm upon activation with ligand treatment. In the cells coexpressing FP
      MR and FP-importin beta, FP-MR moved into the nucleus from the cytoplasm, but the
      distribution of FP-importin beta was little changed upon ligand treatment.
      Analysis of a mutant of MR, in which nuclear localization signal (NLS) is
      inactivated, demonstrated that the intact NLS is necessary for the trafficking of
      MR related to importin alpha. This is the first visual evidence of the nuclear
      import of MR in association with importin alpha in single living cells.

PMID- 15846518
TI  - Hemocyte differentiation in the hematopoietic organs of the silkworm, Bombyx
      mori: prohemocytes have the function of phagocytosis.
AB  - Hemocytes isolated from the larval hematopoietic organs of the silkworm were
      classified following staining with acridine orange and propidium iodide. Among
      the hemocytes isolated from the hematopoietic organs of whole fifth larval and
      wandering stages, most were prohemocytes (60%-70%) and oenocytoids (30%-40%).
      Granulocytes comprised only about 0.5%-1% at the wandering stage and were even
      rarer at other stages; no spherulocytes or plasmatocytes were found. Therefore,
      hemocyte differentiation inside larval hematopoietic organs is not as extensive
      as previously thought. Following 10-30 min in vitro culture of hemocytes isolated
      from larval hematopoietic organs, many young granulocytes and plasmatocytes
      appeared. Furthermore, during phagocytosis assays, prohemocytes were seen to
      adopt the morphology of plasmatocytes, containing fragments of phagocytosed
      cells. Our results underline the similarities between Drosophila and Bombyx
      hematopoiesis.

PMID- 15846519
TI  - Chondrocytes are released as viable cells during cartilage resorption associated
      with the formation of intrachondral canals in the rat tibial epiphysis.
AB  - The development of cartilage canals is the first event of the ossification of the
      epiphyses in mammals. Canal formation differs from vascular invasion during
      primary ossification, since the former involves resorption of resting cartilage
      and is uncoupled from bone deposition. To learn more about the fate of resorbed
      chondrocytes during this process, we have carried out structural, cell
      proliferation, and in situ hybridization studies during the first stages of
      ossification of the rat tibial proximal epiphysis. Results concerning the
      formation of the cartilage canals implied the release of resting chondrocytes
      from the cartilage matrix to the canal cavity. Released chondrocytes had a well
      preserved structure, expressed type-II collagen, and maintained the capacity to
      divide. All these data suggested that chondrocytes released into the canals
      remained viable for a specific time. Analysis of the proliferative activity at
      different regions of the cartilage canals showed that the percentage of
      proliferative chondrocytes at areas of active cartilage resorption was
      significantly higher than that in zones of low resorption. These results are
      consistent with the hypothesis that resting chondrocytes surrounding canals have
      a role in supplying cells for the development of the secondary ossification
      center. Since released chondrocytes are at an early stage of differentiation
      greatly preceding their entry into the apoptotic pathway and are exposed to a
      specific matrix, cellular, and humoral microenvironment, they might differentiate
      to other cell types and contribute to the ossification of the epiphysis.

PMID- 15846520
TI  - Phenological observations on shrubs to predict weed emergence in turf.
AB  - Phenology is the study of periodic biological events. If we can find easily
      recognizable events in common plants that precede or coincide with weed
      emergences, these plants could be used as indicators. Weed seedlings are usually
      difficult to detect in turf, so the use of phenological indicators may provide an
      alternative approach to predict the time when a weed appears and consequently
      guide management decisions. A study was undertaken to determine whether the
      phenological phases of some plants could serve as reliable indicators of time of
      weed emergence in turf. The phenology of six shrubs (Crataegus monogyna Jacq.,
      Forsythia viridissima Lindl., Sambucus nigra L., Syringa vulgaris L., Rosa
      multiflora Thunb., Ziziphus jujuba Miller) and a perennial herbaceous plant
      [Cynodon dactylon (L.) Pers.] was observed and the emergence dynamics of four
      annual weed species [Digitaria sanguinalis (L.) Scop., Eleusine indica (L.)
      Gaertner, Setaria glauca (L.) Beauv., Setaria viridis (L.) Beauv.] were studied
      from 1999 to 2004 in northern Italy. A correlation between certain events and
      weed emergence was verified. S. vulgaris and F. viridissima appear to be the best
      indicators: there is a quite close correspondence between the appearance of D.
      sanguinalis and lilac flowering and between the beginning of emergence of E.
      indica and the end of lilac flowering; emergences of S. glauca and S. viridis
      were predicted well in relation to the end of forsythia flowering. Base
      temperatures and starting dates required to calculate the heat unit sums to reach
      and complete the flowering phase of the indicators were calculated using two
      different methods and the resultant cumulative growing degree days were compared.

PMID- 15846521
TI  - Frequency of emergency room visits for childhood asthma in Ottawa, Canada: the
      role of weather.
AB  - The aim of this study was to evaluate associations between meteorological
      conditions and the number of emergency department visits for asthma in a
      children's hospital in Ottawa, Canada. A case-crossover study design was used.
      Hospital emergency department visits for asthma between 1992 and 2000 were
      identified based on patients' presenting complaints. We obtained hourly measures
      for the following meteorological variables: wind speed, temperature, atmospheric
      pressure, relative humidity, and visibility. Particular emphasis was placed on
      exploring the association between asthma visits and fog, thunderstorms, snow, and
      liquid and freezing forms of precipitation. In total, there were 18,970 asthma
      visits among children between 2 and 15 years of age. The number of visits and
      weather characteristics were grouped into 6 h case and control intervals. The
      occurrence of fog or liquid precipitation was associated with an increased number
      of asthma visits, while snow was associated with a reduced number (P<0.05).
      Stratified analyses by season found no association in any of the four calendar
      intervals between the number of asthma visits and visibility, change in relative
      humidity and change in temperature. In contrast, summertime thunderstorm activity
      was associated with an odds ratio of 1.35 (95% CI=1.02-1.77) relative to summer
      periods with no activity. Models that incorporate calendar and meteorological
      data may help emergency departments to more efficiently allocate resources needed
      to treat children presenting with respiratory distress.

PMID- 15846522
TI  - Use of midazolam and ketamine as sedation for children undergoing minor operative
      procedures.
AB  - OBJECTIVES: We used intravenous midazolam and ketamine for children undergoing
      minor operative procedures with satisfactory results. We aimed to further
      evaluate its efficacy and adverse effects in pediatric ward setting. METHODS:
      This was a prospective study of all children undergoing minor operations with
      sedation in our pediatric general and oncology wards from July 1998 to June 1999.
      The procedures included lumber puncture+/-intrathecal chemotherapy, bone marrow
      aspiration+/-trephine biopsy, central venous catheter removal, skin biopsy, or
      their combination. All sedation procedures were started with midazolam 0.1 mg/kg
      and ketamine 1 mg/kg; they were increased gradually to 0.4 and 4 mg/kg,
      respectively, if necessary. Heart rate and SaO2 were continuously monitored.
      RESULTS: Altogether, 369 minor operations were performed in 112 patients
      (male:female=2:1, median age 6 years, range 5 months-17 years). All achieved
      adequate sedation, with 96% within 30 s and 75% required just the starting dose.
      Younger children required a higher dosage (p=0.003 for midazolam, p<0.001 for
      ketamine). The median recovery time was 87 min, with no association with age,
      sex, or dosage of sedation, but was longer in patients having hallucination
      (p=0.001). Adverse effects included tachycardia (27.9%), increased secretion
      (17.6%), agitation (13.6%), nausea and vomiting (9.2%), hallucination (8.7%),
      desaturation (8.4%), and cataleptic reaction (0.8%). All desaturation episodes
      were transient and responded to oxygen supplement alone. None developed
      bronchospasm or convulsion. Some adverse effects were dose-related. Half of the
      children who received 0.3 mg/kg midazolam developed desaturation. CONCLUSIONS:
      Intravenous midazolam-ketamine can provide rapid, effective, and safe sedation
      for children undergoing minor operations in ward setting. Adverse effects are
      mild. Midazolam above 0.3 mg/kg should be used with caution.

PMID- 15846523
TI  - Experience in the use of the palliative care outcome scale.
AB  - GOALS OF WORK: The objective of the study is to assess the Palliative Care
      Outcome Scale (POS) as a potential audit tool within a specialist cancer centre.
      It also aims to answer the following questions: does the tool identify problem
      areas and demonstrate changes in quality of life over time? How well do staff and
      patient ratings correlate? PATIENTS AND METHODS: The POS questionnaire was
      piloted at a specialist cancer centre. Thirty consecutive patients admitted to
      the palliative care wards and ward staff completed questionnaires on admission
      and twice weekly until discharge or death. A further questionnaire assessed staff
      attitudes. RESULTS: There was a significant improvement in overall patient POS
      score at 1 week (days 5-9). Four "symptoms" or issues were scored as being
      important for our patients: pain, other symptoms, anxiety and patient's
      perception of family anxiety. These all significantly improved within the first
      week. At the initial assessment, staff underestimated patients' pain and
      overestimated problems relating to information giving and patients' ability to
      share their feelings. There was no significant difference between staff and
      patient scores after 1 week. The other six areas covered by the tool were less
      important; this may reflect the patient population seen at our centre. Use of the
      tool identified areas for staff training and effectively demonstrated improvement
      in patient care. CONCLUSION: The POS is an outcome measure tool designed to
      assess physical, psychological, practical and existential aspects of quality of
      life. It may be useful in identifying problems in individual patients and
      directing care to address these needs.

PMID- 15846524
TI  - In pursuit of an artful death: discussion of resuscitation status on an inpatient
      radiation oncology service.
AB  - GOALS OF WORK: Consensus has emerged among health practitioners, legal experts,
      clinical ethicists and the public that end-of-life decisions should be the shared
      responsibility of physicians and patients. In discussion of withholding
      cardiopulmonary resuscitation in cancer patients, however, opinion remains
      divided. We performed a quality assurance investigation on the use of the 'do-not
      resuscitate' (DNR) order on an inpatient radiation oncology service to determine
      how often DNR orders are accompanied by a description of informed consent.
      PATIENTS AND METHODS: Records of patients admitted 1 July to 31 December 2002
      were identified and reviewed to determine the presence or absence of a DNR order.
      Circumstances surrounding the order, including evidence of informed consent, were
      determined. MAIN RESULTS: The study population comprised 96 patients admitted 109
      times. The median age was 64 years, and in 56.0% of admissions, the patient was
      female. In 26.8%, the patient had lung cancer. The intent of admission was
      curative in 53.2%, and palliative in 44.0%. DNR was recorded for 30.2% of
      patients, and there was evidence of informed consent in 41.4%. In 89.7% admission
      was with palliative intent. Nine patients (9.4%) experienced cardiac arrest; all
      were DNR at the time of their event. CONCLUSIONS: While almost one-third of the
      patients on this inpatient radiation oncology service had documented DNR status,
      informed consent appeared to have been obtained in fewer than half. Patient
      involvement in resuscitative decisions should be an ethical obligation. Performed
      well, this may also allow for exploration of patients' needs at the end of life,
      to allow the pursuit of what Nuland terms an 'artful death'.

PMID- 15846526
TI  - Domestic dogs (Canis familiaris) use a physical marker to locate hidden food.
AB  - Dogs can use the placement of an arbitrary marker to locate hidden food in an
      object-choice situation. We tested domestic dogs (Canis familiaris) in three
      studies aimed at pinning down the relative contributions of the human's hand and
      the marker itself. We baited one of two cups (outside of the dogs' view) and gave
      the dog a communicative cue to find the food. Study 1 systematically varied dogs'
      perceptual access to the marker placing event, so that dogs saw either the whole
      human, the hand only, the marker only, or nothing. Follow-up trials investigated
      the effect of removing the marker before the dog's choice. Dogs used the marker
      as a communicative cue even when it had been removed prior to the dog's choice
      and attached more importance to this cue than to the hand that placed it although
      the presence of the hand boosted performance when it appeared together with the
      marker. Study 2 directly contrasted the importance of the hand and the marker and
      revealed that the effect of the marker diminished if it had been associated with
      both cups. In contrast touching both cups with the hand had no effect on
      performance. Study 3 investigated whether the means of marker placement
      (intentional or accidental) had an effect on dogs' choices. Results showed that
      dogs did not differentiate intentional and accidental placing of the marker.
      These results suggest that dogs use the marker as a genuine communicative cue
      quite independently from the experimenter's actions.

PMID- 15846525
TI  - Temperature dependence of methyl-coenzyme M reductase activity and of the
      formation of the methyl-coenzyme M reductase red2 state induced by coenzyme B.
AB  - Methyl-coenzyme M reductase (MCR) catalyses the formation of methane from methyl
      coenzyme M (CH(3)-S-CoM) and coenzyme B (HS-CoB) in methanogenic archaea. The
      enzyme has an alpha(2)beta(2)gamma(2) subunit structure forming two structurally
      interlinked active sites each with a molecule F(430) as a prosthetic group. The
      nickel porphinoid must be in the Ni(I) oxidation state for the enzyme to be
      active. The active enzyme exhibits an axial Ni(I)-based electron paramagnetic
      resonance (EPR) signal and a UV-vis spectrum with an absorption maximum at 385
      nm. This state is called the MCR-red1 state. In the presence of coenzyme M (HS
      CoM) and coenzyme B the MCR-red1 state is in part converted reversibly into the
      MCR-red2 state, which shows a rhombic Ni(I)-based EPR signal and a UV-vis
      spectrum with an absorption maximum at 420 nm. We report here for MCR from
      Methanothermobacter marburgensis that the MCR-red2 state is also induced by
      several coenzyme B analogues and that the degree of induction by coenzyme B is
      temperature-dependent. When the temperature was lowered below 20 degrees C the
      percentage of MCR in the red2 state decreased and that in the red1 state
      increased. These changes with temperature were fully reversible. It was found
      that at most 50% of the enzyme was converted to the MCR-red2 state under all
      experimental conditions. These findings indicate that in the presence of both
      coenzyme M and coenzyme B only one of the two active sites of MCR can be in the
      red2 state (half-of-the-sites reactivity). On the basis of this interpretation a
      two-stroke engine mechanism for MCR is proposed.

PMID- 15846527
TI  - COX-2 selective inhibitors--they are still the best treatment for many patients!

PMID- 15846528
TI  - Reassessment of the benefit/risk-ratio of selective COX-2-inhibitors.

PMID- 15846529
TI  - Pulmonary computed tomography and adult respiratory distress syndrome.
AB  - Computed tomography has completely changed the views and interpretation of ARDS,
      opening a new era in our understanding of the physiological, pathological and
      clinical aspects of this syndrome. In this brief review we will emphasize the
      most relevant new knowledge achieved using CT scanning and we will briefly
      discuss its clinical use in ARDS patients.

PMID- 15846530
TI  - Arrhythmias in patients with surgically treated atrial septal defects.
AB  - Atrial arrhythmias complicate the clinical course of adult patients with an
      atrial septal defect. Atrial flutter is more prevalent in younger patients, and
      frequently regresses after surgical defect closure. Atrial fibrillation however,
      which results from a chronic underlying disease, rarely reverts to sinus rhythm
      after surgical repair. While younger patients with atrial flutter clearly benefit
      from defect closure alone, this is not evident in older patients with
      fibrillation, who may need an additional anti-arrhythmic procedure concomitant to
      defect closure.

PMID- 15846531
TI  - Binge drinking in 19 year old men.
AB  - QUESTION UNDER STUDY: To describe alcohol use, binge drinking and drinking
      consequences in 19 year old men. METHODS: During a one-day army recruitment
      process mandatory for all Swiss males, a convenience sample of 1,004 men
      completed the "Health and Lifestyle Questionnaire", assessing demographics,
      alcohol use, binge drinking, and drinking consequences over the last 12 months.
      Binge drinking was defined as having 5 or more drinks on a single occasion at
      least once over the last 12 months. Among the 1,004 subjects, binge drinking
      could not be defined in 123 (12.3%) due to "don't know" responses, leaving 881
      subjects with complete data. RESULTS: Of the 881 subjects, 690 (78.3%) reported
      binge drinking at least once over the last 12 months, 269 (30.5%) with infrequent
      binge drinking (< or = 1x/month) and 421 (47.8%) with frequent binge drinking (>
      or = 2x/month). In addition, 379 (43.0%) of the subjects experienced 3 or more
      drinking consequences over the last 12 months and the number of these
      consequences increased as the frequency of binge drinking increased (trend
      analyses significant for 9 of the 12 consequences evaluated). Among the 687
      subjects with moderate average alcohol intake (< 14 drinks per week), 252 (36.7%)
      reported infrequent binge drinking, of whom 82 (32.5%) experienced 3 or more
      adverse drinking consequences over the last 12 months, whereas 246 (35.8%)
      reported frequent binge drinking and 128 (52.0%) of these experienced 3 or more
      adverse drinking consequences. CONCLUSIONS: Binge drinking in this sample of
      young men is frequent and is associated with numerous consequences, even among
      those consuming moderate amounts of alcohol.

PMID- 15846532
TI  - Head injury after a fall on stairs: poorer prognosis in inebriated patients?
AB  - AIM: The aim of the present study was to determine whether inebriated patients
      falling on stairs sustain more severe head injuries than sober patients because
      of a delayed reaction time and a pathological coagulation and clotting system.
      PATIENTS AND METHODS: The files of 140 head-injured patients who came to
      admission after falling on stairs were retrospectively reviewed with respect to
      demographic data, initial Glasgow coma scale (GCS) score, type of hematoma,
      coagulation parameters and outcome (death versus survival, Glasgow Outcome Scale
      [GOS] score GOS 3-5 vs. GOS 1 and 2). RESULTS: There were 69 patients who had an
      alcohol level of > or = 0.8 parts per thousand at the time of the fall (49.0 %).
      The mortality in the group of inebriated patients was 12.9 %, in the group of
      sober patients 33.3 % (p = 0.001). The characteristics of the two groups were
      comparable, except for age (50.4 vs. 69.1 years, p = 0.001). The analysis of
      mortality in relation to age confirmed the finding of a lower mortality rate in
      inebriated patients. CONCLUSION: The hypothesis that inebriated patients sustain
      more severe head injuries with higher mortality rates could not be validated.
      Routine laboratory tests did not detect coagulation and clotting disorders in
      inebriated patients. Instead, our study again showed that age is one of the major
      prognostic factors in head injury.

PMID- 15846533
TI  - Microsurgical repair of the facial nerve.
AB  - OBJECTIVE: To report a series of 18 patients who underwent microsurgical repair
      of the facial nerve using different techniques and to discuss the indications and
      results of facial reinnervation procedures. METHODS: Eighteen patients with post
      surgical facial palsy underwent facial reinnervation using different
      techniques.'These included classic hypoglossal-facial anastomosis in 13 cases,
      one-stage hemihypoglossal-intratemporal facial nerve anastomosis and
      translabyrinthine removal of residual intra-canalar acoustic schwannoma in 3,
      hemihypoglossal-facial nerve anastomosis in one, and neurotization of facial
      muscles through a nerve graft in one. RESULTS: The facial muscle function
      improved in all patients, up to grade III in 7 cases (39 %), grade IV in 9 (50 %)
      and grade V in 2 (11 %). The tongue atrophy was minimal in 70.5 %, moderate in
      17.5 % and severe in 12 %. The outcome was better in younger patients (less than
      40 years of age) and in those with a lesser grade of preoperative facial
      impairment. CONCLUSIONS: The classic hypoglossal-facial anastomosis is the
      technique of choice in most cases. The use of the intratemporal facial nerve is
      indicated when removal of an intra-canalar residual schwannoma must also be
      performed. The neurotization of the facial muscles through a nerve graft may be
      used when there is no distal trunk of the facial nerve available for the
      anastomosis.

PMID- 15846534
TI  - Accidental dural tears occurring during supratentorial craniotomy -- a
      prospective analysis of predisposing factors in 100 patients.
AB  - OBJECT: Accidental dural tears during craniotomy constitute a possible source of
      CSF leakage and wound infection. This can turn an elective procedure into a
      complicated and cost-intensive problem. Only a few studies have addressed the
      incidence of dural tears, but there have been many studies dealing with various
      techniques that can be employed to repair dural tears. The present study was
      carried out to analyze predisposing factors for dural tears during trepanation in
      order to optimize the design of a robot-assisted trepanation system. PATIENTS:
      100 patients were analyzed prospectively. An evaluation sheet was designed to
      document size and location of the lesion and the craniotomy, the geometry and
      number of burr holes, and the auxiliary tools used during bone flap removal.
      Furthermore, the suspected histology was noted and anatomical facts, including
      cranial vault thickness and the presence of hyperostosis frontalis interna, were
      documented. RESULTS: In 100 craniotomies performed, in the majority of cases (64
      %), in order to gain access to intracerebral lesions, 30 dural tears were seen,
      involving both dural layers in 26 cases. There were 26 tears located under the
      margins of the craniotomy; the length was 0-3 cm in 18 patients (69 %).
      Significant predisposing factors were the thickness of the cranial vault and the
      presence of a hyperostosis frontalis. Furthermore, the location (frontal) and the
      diagnosis of an extracerebral pathology, including meningiomas, were significant
      factors for dural tears. Elderly patients and the use of the drill to complete
      the trepanation were also significant predisposing factors. Dural repair was done
      using suturing, in most of the cases combined with a free periostal flap. Central
      dural tears were integrated into the planned dural opening. A vascularized flap
      or muscle was used in the minority of cases. Postoperative cerebral fluid leakage
      was seen in two patients, wound infections in three. CONCLUSIONS: Dural tears
      occurring during craniotomy cannot be prevented, when predisposing factors are
      taken into account. The absence of brain damage may due to two factors: 1) in
      elderly patients with hyperostosis, an additional atrophy of the brain is
      present; 2) extracerebral tumors, with their space-occupying growth, shift the
      underlying brain away from the calvaria. Considering the design of a robot
      assisted trepanation system, the following conclusions seem possible: dural tears
      cannot be avoided because predisposing factors are overriding. For improved
      safety, additional, specialized instrumentation is required.

PMID- 15846535
TI  - Ethical aspects of use of fetal/embryonic cells in treatment and research.
AB  - The use of cells derived from in vitro embryos or aborted human fetuses raises
      serious moral questions for doctors and researchers. It is not enough to
      anticipate good from such use: morality is concerned not merely with outcome, but
      with choices and their impact on character. The human moral subject is the human
      organism, who has rights and interests from the beginning of his or her
      existence. Harvesting cells or tissue from an embryo or fetus who is deliberately
      destroyed -- in some cases, by the harvesting itself -- is a violation of the
      rights of the individual concerned. To accept cells or tissue from those who did
      the harvesting (as opposed to using a much older cell-line) is to give the
      impression that we condone the harvesting, and indeed the taking of the donor's
      life. Irrespective of the medical benefits for which we may be hoping, we cannot
      relieve the suffering of one human individual by exploiting another.

PMID- 15846536
TI  - [Recommendations for the management of patients with aneurysmal subarachnoid
      hemorrhage].
AB  - After SAH, primary and secondary complications are frequent and often require
      neurosurgical interventions to avoid secondary brain damage. The authors of the
      present paper have summarized the available data about the treatment modalities
      often used for patients with SAH. The present recommendations have been developed
      as a neurosurgical and neuroanestesiological consensus. Evidence from
      prospective, randomized, double blind, placebo-controlled studies support grade A
      recommendations (standard) for the prophylaxis and treatment of cerebral
      vasospasm with oral Nimodipine in good grade patients. For intravenous Nimodipine
      or for oral nimodipine treatment in poor grade patients, available data only
      support grade C recommendations (options). Despite the lack of data supporting
      standards (grade A) or guidelines (grade B), avoidance and rigorous treatment of
      hypotension and hypovolemia remains the mainstay in the prophylaxis and treatment
      of a delayed ischemic neurological deficit (DIND). Prophylactic hypervolemia or
      prophylactic hypertension and hypervolemia was shown to be ineffective in
      reducing symptomatic vasospasm and improving outcome (grade B). Therapeutic
      hypertensive hypervolemic hemodilution is recommended as a treatment of
      symptomatic vasospasm but no prospective studies are available (grade C
      recommendation). Suggested target values for moderate triple-H-therapy are CPP 80
      120 mmHg (MAP 90-130), CVP > 7 mmHg and Hk 0.25-0.40. Balloon angioplasty should
      be considered for treatment of DIND cause by focal, proximal cerebral vasospasm.
      There is no evidence supporting the routine use of antifibrinolyticals, steroids
      or anticonvulsive prophylaxis. Clinical data indicate that current prophylaxis
      and treatment of cerebral vasospasm is still insufficient and aggressive triple-H
      therapy is associated with an increased incidence of complications.

PMID- 15846537
TI  - Ceftriaxone-induced symptomatic pseudolithiasis mimicking ICP elevation.
AB  - In neurosurgery, ceftriaxone is a widely used, third generation cephalosporin for
      the treatment of CNS infections and perioperational prophylaxis. Recent studies
      have demonstrated that ceftriaxone induces reversible precipitates in the
      gallbladder. This complication is referred to as "biliary pseudolithiasis", and
      it has symptoms similar to the raised intracranial pressure (ICP) symptoms of the
      perioperative period. Symptomatic biliary pseudolithiasis should be kept in mind
      in all pediatric neurosurgery cases under ceftriaxone therapy in order to prevent
      unnecessary postoperative investigations and surgery.

PMID- 15846538
TI  - Tuberculosis of the craniocervical junction: a case report.
AB  - Craniocervical tuberculosis (TB) is very rare. Despite the use of magnetic
      resonance imaging (MRI) and cranial tomography (CT), diagnosis of craniocervical
      tuberculosis is frequently difficult. In this study, we present a craniocervical
      tuberculosis abscess case which demonstrates the role of transoral surgery for
      both diagnosis and treatment.

PMID- 15846539
TI  - [Hearing disorder. Conservative management].

PMID- 15846540
TI  - [Hearing disorder. Surgical management].

PMID- 15846541
TI  - [Hearing disorder. Mechanical management of hearing loss: conventional and
      implantable hearing aids].

PMID- 15846542
TI  - [Hearing disorder. Mechanical management of hearing loss: cochlear implants and
      brain stem implants--current developments in the last 10 years].

PMID- 15846544
TI  - [Impaired sense of smell and taste. Therapy options in anosmia and dysgeusia].

PMID- 15846543
TI  - [Dysequilibrium. Restorative management in dysequilibrium].

PMID- 15846545
TI  - [Impaired function of the upper respiratory tract. Restorative procedures for
      upper airway dysfunction, nasal breathing].

PMID- 15846546
TI  - [Impaired function of the upper airways. Pharyngeal breathing/snoring].

PMID- 15846547
TI  - [Impaired function of the upper airways. Laryngeal breathing].

PMID- 15846548
TI  - [Impaired motor functions. Surgical and conservative procedures for restoring
      motor functions of the facial nerve, accessory nerve, hypoglossal nerve].

PMID- 15846549
TI  - [Impaired swallowing and inadequate nutrition].

PMID- 15846550
TI  - [Impaired sensation. Trigeminal neuralgia].

PMID- 15846551
TI  - [Voice disorder. Conservative management].

PMID- 15846552
TI  - [Voice disorder. Surgical procedures].

PMID- 15846553
TI  - [Speech dysfunction. Reconstructive procedures in speech dysfunction (dysarthria,
      dysglossia)].

PMID- 15846554
TI  - [Voice and speech dysfunction. Reconstructive procedures after total
      laryngectomy].

PMID- 15846555
TI  - [Skin dysfunction. Conservative reconstructive procedures].

PMID- 15846556
TI  - [Compromised protective function of facial skin. Surgical treatment of
      compromised facial skin function].

PMID- 15846557
TI  - [Impaired chewing dysfunction. Reconstructive procedures in impaired chewing
      dysfunction].

PMID- 15846558
TI  - [The cervical spine--disorders of the craniocervical transition].

PMID- 15846559
TI  - [Psychosomatic disorders. Therapeutic management of psychosomatic disorders of
      the ENT area].

PMID- 15846560
TI  - [S3-guideline conference "Colorectal Cancer" 2004].

PMID- 15846563
TI  - Ovarian cysts in infants and children.
AB  - The etiology of ovarian cysts varies with the developmental stage and hormonal
      milieu of the patient. In general, most ovarian cysts are functional in nature
      and usually resolve without treatment. Treatment is indicated if the diagnosis is
      in question, the cyst persists, or the patient is symptomatic. Laparoscopy has
      become the approach favored by most pediatric surgeons for the treatment of
      ovarian cysts. All surgical procedures for ovarian cysts should spare functional
      ovary as much as is technically possible. Simple cysts should be fenestrated.
      Complex or functional cysts should be excised, with preservation of the remaining
      ovary.

PMID- 15846561
TI  - Heterozygous mutations of OTX2 cause severe ocular malformations.
AB  - Major malformations of the human eye, including microphthalmia and anophthalmia,
      are examples of phenotypes that recur in families yet often show no clear
      Mendelian inheritance pattern. Defining loci by mapping is therefore rarely
      feasible. Using a candidate-gene approach, we have identified heterozygous coding
      region changes in the homeobox gene OTX2 in eight families with ocular
      malformations. The expression pattern of OTX2 in human embryos is consistent with
      the eye phenotypes observed in the patients, which range from bilateral
      anophthalmia to retinal defects resembling Leber congenital amaurosis and
      pigmentary retinopathy. Magnetic resonance imaging scans revealed defects of the
      optic nerve, optic chiasm, and, in some cases, brain. In two families, the
      mutations appear to have occurred de novo in severely affected offspring, and, in
      two other families, the mutations have been inherited from a gonosomal mosaic
      parent. Data from these four families support a simple model in which OTX2
      heterozygous loss-of-function mutations cause ocular malformations. Four
      additional families display complex inheritance patterns, suggesting that OTX2
      mutations alone may not lead to consistent phenotypes. The high incidence of
      mosaicism and the reduced penetrance have implications for genetic counseling.

PMID- 15846564
TI  - Ovarian torsion.
AB  - Ovarian torsion is a rare problem in the pediatric age group that must be
      included in the differential diagnosis of any girl with abdominal pain or a
      pelvic or abdominal mass. Clinical presentation is nonspecific, and diagnosis is
      based on a high index of suspicion. Ultrasound scan remains the most useful
      investigation, but blood flow on Doppler examination does not exclude ovarian
      torsion. Current recommendations of treatment strongly support ovary
      conservation, and macroscopic appearance of the ovary is not a reliable indicator
      of the degree of necrosis and potential for ovary recovery. For children with
      ovarian torsion, laparoscopic detorsion should be performed with strong
      consideration of oophoropexy. An underlying ovary lesion such as mature teratoma
      or functional cyst is found in most cases; however, the risk of cancer in these
      patients is extremely low. If there is concern of a mass or underlying pathology,
      then follow-up ultrasound, resolution of edema and interval laparoscopic
      treatment may be required.

PMID- 15846565
TI  - Benign ovarian masses.
AB  - Primary tumors of the ovary are uncommon in children and the majority of these
      masses are not malignant. As newer diagnostic imaging techniques have increased
      the detection of all ovarian masses, the frequency of ovarian cancer has actually
      decreased. Clinical symptoms are generally not helpful in distinguishing benign
      from malignant masses, but radiographic criteria have been developed. Surgical
      treatment is aimed at ovarian preservation if the lesion proves benign.

PMID- 15846566
TI  - Malignant lesions of the ovary in childhood.
AB  - Approximately half of all lesions of the ovary in childhood are neoplastic, yet
      only a small fraction of neoplastic lesions contain malignant elements. Overall,
      malignancies of the ovary account for 10% of all ovarian masses and 1% of
      childhood cancers. Primary ovarian malignancies fall into three broad categories
      based on the cell type of origin. Germ cell tumors predominate and may be further
      subdivided based on the differentiation of the malignant cells. Epithelial cell
      tumors, which are most common in adults, and sex-cord stromal tumors each make up
      15% of the total in children. Rare malignant lesions and metastatic disease
      account for the small remaining group of tumors. Regardless of tumor type, the
      majority of patients present with localized disease, but proper surgical staging
      is important to determine the need for adjuvant therapy. The development of
      platinum-based chemotherapeutic regimens has resulted in significant improvements
      in long-term survival, even for children who present with advanced stage disease.

PMID- 15846567
TI  - Surgical management of the incidentally identified ovarian mass.
AB  - Due to the widespread use of sophisticated and detailed diagnostic imaging,
      pediatric surgeons may encounter incidental ovarian masses on preoperative
      imaging obtained for abdominal pain, trauma or other indications. Surgeons may
      also encounter unexpected ovarian masses at laparotomy or laparoscopy. Operative
      management differs based on the size, type of lesion (cystic, solid or mixed) as
      well as the age of the child. Neonatal cystic lesions may not require therapy
      whereas a solid ovarian mass in an adolescent requires appropriate evaluation to
      differentiate benign from malignant disease. Intraoperative and preoperative
      evaluation, staging, and management of incidentally identified ovarian masses in
      children and adolescents will be reviewed.

PMID- 15846568
TI  - Polycystic ovary syndrome in adolescent girls.
AB  - Polycystic ovary syndrome (PCOS) has traditionally been thought of as a triad of
      oligomenorrhea, hirsutism, and obesity. PCOS is now recognized as a heterogeneous
      disorder that results in overproduction of androgens primarily from the ovary
      leading to anovulation and hirsutism and is associated with insulin resistance.
      Symptoms in the adolescent include oligomenorrhea, hirsutism, acne, and weight
      gain. These symptoms are often attributed to normal pubertal events, which can
      lead to a delay in diagnosis. Insulin resistance, impaired glucose tolerance and
      diabetes have been shown to occur in adolescents with PCOS. Treatment should be
      instituted early to decrease symptoms and long-term sequellae of PCOS. Weight
      loss, oral contraceptives and antiandrogens are very effective in treating the
      symptoms of this disorder. Insulin-sensitizing medications show promise, but
      should be used with caution until larger randomized trials have shown short- and
      long-term benefit and efficacy over traditional therapies in the adolescent
      population.

PMID- 15846569
TI  - Evaluation and management of the abnormal gonad.
AB  - Diagnostic evaluation of patients with an abnormal gonad is complex because of
      multifactoral etio-pathogenesis and rarity of the conditions. In the text to
      follow, we have briefly discussed the embryology and attempted to classify
      abnormal gonadal disorders. The aims of evaluating such a child are to: (1)
      establish genetic sex; (2) determine the hormonal milieu; (3) evaluate the
      anatomy of internal and external genitalia and gonads; and (4) in older children,
      assess the phenotypic and psychological sex. In newborn children with ambiguous
      genitalia, the focus is now on accurate gender assignment. A team approach is
      needed and decisions are based on likely prognosis for behavior and gender
      orientation. The recent advances in cytogenetics have proven to be helpful in
      early and accurate diagnosis. In patients with an abnormal gonad, four conditions
      can present with sexual ambiguity at birth: female pseudohermaphroditism (or
      "virilized female"), true hermaphroditism, male pseudohermaphroditism (or
      "undervirilized male") and mixed gonadal dysgenesis. The role of clinical history
      and examination is emphasized in differential diagnosis and management. Timing of
      surgery for each of the conditions is discussed.

PMID- 15846570
TI  - Paratubal and tubal abnormalities.
AB  - The fallopian tubes are the essential genital ducts that convey the female sex
      cells for fertilization. They are differentiated and detectable early in fetal
      life. There are numerous paratubal and tubal abnormalities that can occur at any
      point in the female life. Some of these are rare but may initiate significant
      morbidity and/or manifest as life-threatening clinical problems. A comprehensive
      understanding of symptoms, diagnosis, optimal imaging modalities, and medical and
      surgical management is vital to identify the best treatment option. The clinical
      entities described in this article include torsion, hydatids of Morgagni,
      paraovarian cysts, infections including tuboovarian abscess/pyosalpinx and
      salpingitis isthmic nodosa, ectopic pregnancy, tumors, and genetic disorders.

PMID- 15846572
TI  - Complex interactions: the immunogenetics of human leukocyte antigen and killer
      cell immunoglobulin-like receptors.
AB  - The killer cell immunoglobulin-like receptors (KIR) for human leukocyte antigen
      (HLA) modulate innate and adaptive immunity by controlling effector cells. HLA
      and KIR are encoded in genomic regions that have complex organization and exhibit
      exceptional diversity within and among human population groups. This diversity is
      likely to have arisen to combat a constantly evolving pathogen challenge.
      Numerous variations influence the expression level or function of KIR molecules
      and can affect their interaction with HLA, with important implications for the
      immune response. The functional variety of natural immune responses that are
      controlled by HLA and KIR interactions is genetically determined and maintained
      by natural selection.

PMID- 15846573
TI  - Human leukocyte antigen matching in unrelated donor hematopoietic cell
      transplantation.
AB  - Hematopoietic cell transplantation (HCT) from unrelated donors is a curative
      therapy for many malignant and nonmalignant blood disorders. The success of
      unrelated HCT is influenced by the degree of human leukocyte antigen (HLA)
      compatibility between the donor and patient. When donor matching for HLA alleles
      is feasible, overall transplant outcome is superior. The presence of donor
      recipient mismatching is associated with increased risk of post-transplant
      complications including graft rejection, acute and chronic graft-versus-host
      disease (GVHD), and mortality; these risks are increased with multiple HLA
      mismatches. For the majority of patients who lack HLA-matched unrelated donors,
      current research is focused on the identification of permissible HLA mismatches.
      The influence of nongenetic factors on the tolerability of HLA mismatching has
      recently become evident, demonstrating a need for the integration of both genetic
      and nongenetic variables in donor selection.

PMID- 15846574
TI  - Human leukocyte antigen matching in cord blood transplantation.
AB  - Cord blood transplants are now widely used for allogeneic hematopoietic stem cell
      transplants (HSCT) in patients with various hematologic disorders. One advantage
      of this source of stem cells is the decrease of graft-versus-host disease (GVHD)
      because of the immaturity of lymphocytes at birth. The role of human leukocyte
      antigen (HLA) for donor search and post-transplant outcomes is not very well
      described. The Eurocord Registry has analyzed more than 1,000 cases of unrelated
      cord blood transplants (UCBT). Results show that HLA matching is important for
      engraftment and graft versus leukemia but not for survival and GVHD. Allelic
      matching for HLA-A, -B, -C, -DRB1, and -DQB1 shows that the number of mismatches
      is very high and does not allow identification of prognostic factors. Contrary to
      the criteria of donor choice for an unrelated bone marrow transplant where HLA
      allelic matching is important, in the case of cord blood transplants the number
      of nucleated cells infused is the most important predictor of success.

PMID- 15846575
TI  - Natural killer cell receptors: regulating innate immune responses to hematologic
      malignancy.
AB  - Critical to innate immunity, the natural killer (NK) cell performs its function
      of immunosurveillance through its recognition of altered or missing self on
      damaged, infected, or transformed malignant cells. NK cell receptors responsible
      for detection of human leukocyte antigen (HLA) class I and class I-like proteins
      on potential target cells transmit inhibitory and activating signals that
      integrate to determine NK cell function. Advances in the fields of NK cell
      receptor biology and immunogenetics have enhanced our understanding of NK cell
      target recognition and may now guide studies to determine NK cell effects in the
      clinical setting. Analysis of NK cell receptor-ligand relationships, such as the
      inhibitory killer immunoglobulin-like receptors (KIRs) and their HLA class I
      ligands, has revealed the potential for NK cell-mediated benefit in allogeneic
      hematopoietic stem cell transplantation for hematologic malignancies.

PMID- 15846576
TI  - The effect of noninherited maternal antigens in allogeneic transplantation.
AB  - Confrontation of the unborn child immune system with the noninherited maternal
      antigens (NIMAs) has a lifelong modulating impact on the immune response of the
      child against the NIMAs. In this review we summarize the clinical evidence for
      the existence of the NIMA effect, discuss the possible cellular and molecular
      basis of the phenomenon, and outline the necessity of further clinical research.

PMID- 15846577
TI  - Human leukocyte antigen haploidentical hematopoietic stem cell transplantation:
      indications and tentative outcomes in Japan.
AB  - The stem cell banking system in Japan by the Japan Marrow Donor Program (JMDP)
      and Japan Cord Blood Bank Network (JCBBN) has provided increased opportunities
      for patients who might benefit from stem cell transplant from allogeneic sources
      but who lack human leukocyte antigen (HLA)-matched related donors. Nevertheless,
      most patients probably do not undergo transplantation because of the absence of
      suitable stem cell sources. To fulfill this potential need, the outcomes of
      transplants from HLA-mismatched relatives with or without T-cell depletion were
      retrospectively analyzed: the rates of engraftment and survival were insufficient
      in transplants with T-cell depletion, and the actual increase in transplantable
      donor numbers was small because only a single locus mismatched donor was the
      realistic choice in those without T-cell depletion. Since prophylaxis with
      tacrolimus reduced the incidence of grade I-IV acute graft-versus-host disease
      (GVHD) in HLA class I allele mismatched unrelated donors, we studied
      transplantation from HLA one haploidentical family donors who showed
      microchimerism of noninherited maternal antigens, without T-cell depletion but
      with tacrolimus prophylaxis. The rates of engraftment and survival in this
      circumstance were similar to those obtained with transplantation from HLA-matched
      sibling donors.

PMID- 15846579
TI  - Management of anemia associated with myelodysplastic syndrome.

PMID- 15846580
TI  - Monitoring and treatment of iron overload: state of the art and new approaches.

PMID- 15846581
TI  - Overcoming the challenge of patient compliance with iron chelation therapy.

PMID- 15846583
TI  - Iron overload in thalassemia and sickle cell disease.

PMID- 15846582
TI  - Treating iron overload: the state of the art.

PMID- 15846584
TI  - Ayurvedic medicine: it is "time" for scientifically sound studies.

PMID- 15846585
TI  - Ayurvedic medicine for rheumatoid arthritis: a systematic review.
AB  - OBJECTIVE: To systematically review all randomized controlled trials (RCTs) on
      the effectiveness of Ayurvedic medicine for rheumatoid arthritis (RA). METHODS:
      Computerized literature searches for all RCTs of Ayurvedic medicine for RA in the
      following databases: Medline (March 1969 to March 2003), Embase (February 1985 to
      February 2003), AMED (March 1980 to March 2003), Cochrane Controlled Trial
      Register (October 1997 to March 2003), and the abstract service of Central
      Council for Research in Ayurveda and Siddha (CCRAS; 1976 to March 2003). Hand
      searches were performed in 1 Sri Lankan and 3 Indian journals and the authors'
      personal files. Key data of included studies were extracted and reviewed. The
      methodological quality of all studies was evaluated with the Jadad scale.
      RESULTS: Seven studies met our inclusion criteria. Trials tested either Ayurvedic
      medicine against placebo or other Ayurvedic medicines. In general, patient and
      physician global assessments on the severity of pain, and morning stiffness were
      used as endpoints. Of 3 placebo-controlled RCTs, 1 high-quality trial did not
      show benefit of the active treatment against placebo, while another incompletely
      reported study indicated beneficial effects of an Ayurvedic medicine. A further
      incompletely reported study showed no significant difference. The remaining 4
      trials were difficult to interpret because they tested an Ayurvedic medicine
      against other Ayurvedic medicines whose effects were not proven. CONCLUSION:
      There is a paucity of RCTs of Ayurvedic medicines for RA. The existing RCTs fail
      to show convincingly that such treatments are effective therapeutic options for
      RA.

PMID- 15846586
TI  - Epidemiology of systemic sclerosis in northwest Greece 1981 to 2002.
AB  - OBJECTIVES: To investigate the incidence and prevalence, as well as the mortality
      and survival rates, of systemic sclerosis (SSc) in a defined area of northwest
      Greece with a population of about 500,000 inhabitants. MATERIALS AND METHODS:
      Cases have been recorded from the following sources: (1) inpatients and
      outpatients referred to the Rheumatology Clinics of the Ioannina University
      Hospital and the Ioannina General Hospital; (2) patients referred to the private
      rheumatologists practicing in the study area. All patients recorded between
      1/1/1981 and 31/12/2002, resident in the study area, were included in the study.
      Diagnosis was based on the American College of Rheumatology classification
      criteria for SSc. Incidence and prevalence rates were calculated as number of
      cases per 10(5) inhabitants. Population data were based on the National Census of
      1981, 1991, and 2001. RESULTS: The age-adjusted prevalence of SSc was 15.40
      cases/10(5) inhabitants on 31/12/2002. A total of 109 new cases were diagnosed
      during the study period, giving a mean annual age-adjusted incidence rate of 1.10
      cases/10 5 inhabitants. There were 98 women and 11 men, giving a ratio of 8.9/1.
      Limited SSc was diagnosed in 75% and diffuse in 25% of the patients. Esophageal
      involvement was found in 59%, lung involvement in 56%, and renal disease in 5%.
      Thirty-six deaths were recorded during the study period in this incidence cohort.
      The 5-year survival rate was 83% and the 10-year survival rate was 70%.
      CONCLUSIONS: The incidence and prevalence of SSc in northwest Greece were found
      to be lower than those of the USA and Australia, and higher than those of
      northern European countries and Japan. The survival rates were similar to those
      reported by other studies.

PMID- 15846587
TI  - Echocardiographic alterations in systemic sclerosis: a longitudinal study.
AB  - OBJECTIVE: To investigate the evolution of cardiac alterations in systemic
      sclerosis (SSc). METHODS: Echocardiographic and echo-Doppler findings from 77
      unselected SSc patients were analyzed at the first clinical observation and after
      a follow-up period of 65 +/- 36 months. Data were compared with those obtained
      from 45 normal subjects matched for age and sex. RESULTS: Baseline left
      ventricular (LV) systolic function was normal in all patients and controls while
      LV diastolic dysfunction (expressed by an inverted E/A ratio which represents
      early and late filling of the LV during atrial contraction) was present in 23
      patients and in 1 control ( P < 0.001). At the end of the follow-up period, while
      LV systolic function declined in 1 case alone, 6 further patients developed an
      inverted E/A ratio. Moreover, in the group of SSc patients mean A-wave values,
      E/A ratio, left atrial dimension, and LV wall thickness significantly changed,
      all indicating the progression of heart involvement. The alteration of LV
      diastolic function was independent of other known causes potentially affecting LV
      relaxation. Moreover, impairment of LV filling parameters was detected in the
      first phase of follow-up, while the anatomical changes occurred in the last
      phase. CONCLUSIONS: Our data confirm the significant prevalence of LV diastolic
      dysfunction in SSc patients and the role of primary myocardial involvement. The
      long-term follow-up demonstrates that LV filling dysfunction is progressive and
      precedes the occurrence of LV remodeling.

PMID- 15846588
TI  - Postirradiation morphea and subcutaneous polyarteritis nodosa: case report and
      literature review.
AB  - OBJECTIVE: To describe a case of postirradiation morphea and subcutaneous
      polyarteritis nodosa occurring simultaneously in a patient and to review the
      literature on postirradiation autoimmune phenomenon and the potential
      pathogenesis of such changes. METHODS: A 75-year-old woman with breast cancer
      treated with chemotherapy and radiation who developed postirradiation morphea and
      subcutaneous polyarteritis nodosa, both inside and outside of the field of
      radiation, is described. Literature searches were performed on postirradiation
      morphea and other radiation-related inflammatory cutaneous conditions and the
      potential pathogenic mechanisms involved. RESULTS: Twenty-five cases of
      postirradiation morphea and 8 cases of postirradiation panniculitis were reported
      in the literature. Only 3 cases of morphea with distant vasculitis occurring in
      the same patient have been reported and each of these patients had features
      suggestive of an underlying connective tissue disease. This is the first case of
      morphea and subcutaneous polyarteritis nodosa occurring in the same location both
      inside and outside the field of radiation. CONCLUSIONS: Postirradiation morphea
      is an uncommon condition but is being increasingly recognized. Related phenomena
      following radiation include postirradiation panniculitis and now postirradiation
      subcutaneous polyarteritis nodosa. Radiation may be responsible for inducing some
      of the pathogenic changes seen in scleroderma and other autoimmune diseases.
      Rheumatologists should be aware of these potential complications of radiation
      treatment.

PMID- 15846589
TI  - Immunogenetics of primary Sjogren's syndrome in Colombians.
AB  - OBJECTIVE: Data concerning the immunogenetic characteristics of primary Sjogren's
      syndrome (SS) in Latin-Americans are scarce. A research project centered on
      primary SS in Colombians was initiated in January 1996 to better define these
      characteristics. METHODS: TAP, HLA, IL-10, and microsatellites on 6p21.3
      genotyping was performed by polymerase chain reaction techniques.
      Immunohistochemistry for Bcl-2 antagonist/killer (Bak) was performed.
      Autoantibodies and serum level of cytokines (IL-10, TNF-alpha, IFN-gamma, IL-4,
      and IL-12p70) were determined by enzyme-linked immunosorbent assay. RESULTS: The
      HLA-DRB1*0301-DQB1*0201 haplotype was associated with disease (OR = 4.3, 95% CI:
      1.6 to 11.9, P = 0.002), with a more severe histopathologic picture, and with the
      presence of anti-Ro and anti-La antibodies. D6S439 microsatellite polymorphism
      was associated with primary SS in an HLA-independent manner. The most likely gene
      related to the D6S439 chromosomal location appears to be BAK-1 , which codes for
      Bak protein, expressed in salivary gland's infiltrate from patients with primary
      SS but not in controls. IL-10 and IFN-gamma concentrations were significantly
      higher in patients than in controls ( P < 0.01). IL-10 correlated with titers of
      IgA rheumatoid factor, anti-Ro, and anti-La antibodies, and with the severity of
      lymphocytic infiltrate (r > 0.3, P < 0.04). Patients who produced high IL-10
      levels had significantly more episodes of cutaneous vasculitis and a higher
      proportion the IL-10.G9 allele. CONCLUSIONS: The HLA-DRB1*0301-DQB1*0201
      haplotype and IL-10 participate in the histopathological progression of SS,
      autoantibody production, and clinical manifestations. Bak protein and its gene
      polymorphism may participate in the pathology and susceptibility of disease. HLA
      and cytokine (IL-10 and IFN-gamma) manipulation may be helpful in treating
      patients with primary SS.

PMID- 15846590
TI  - Therapeutic options for refractory massive pleural effusion in systemic lupus
      erythematosus: a case study and review of the literature.
AB  - OBJECTIVES: Massive refractory pleural effusions are uncommon in patients with
      systemic lupus erythematosus. Describing such a patient, the literature was
      reviewed to report the various therapeutic options in such cases. METHODS:
      MEDLINE search using the terms "lupus" and "pleural effusion," inclusion of cases
      with refractory massive effusions with emphasis on treatment. RESULTS: Only 10
      such cases (including the patient described here) were reported in the English
      literature over the past 25 years. Those 10 patients suffered symptoms related to
      pleural effusion for a long period of time until resolution, ranging between 2
      months to 2.5 years (median 6 months). During that period of time they underwent
      multiple fluid aspirations. Seven different types of therapy were reported in
      these case descriptions. They can be divided into 2 major groups: systemic
      therapy (immunosuppressive therapy, plasmapheresis, and intravenous
      immunoglobulin) and local therapy (intrapleural steroid injections, pleurodesis
      with talc or tetracycline, and pleurectomy). Pleurodesis with talc seemed to be
      the most effective treatment modality. CONCLUSIONS: Due to the small number of
      reported patients, the best type of intervention is uncertain. When refractory
      pleural effusion is part of lupus exacerbation, the treatment of choice would be
      systemic, such as immunosuppressive therapy with high-dose steroids and
      cyclophosphamide. Intravenous immunoglobulin may also be considered. Local
      measures such as talc pleurodesis should be employed if systemic measures fail,
      or when pleural effusion is the only manifestation of lupus.

PMID- 15846591
TI  - Radiation exposure in rheumatology practice.
AB  - BACKGROUND: Patients encountered in rheumatology practice often have concerns
      about radiation exposure from the imaging procedures used to diagnose and monitor
      their diseases. However, such imaging procedures normally deliver radiation doses
      that are associated with only a low level of risk. OBJECTIVES: To review and
      quantify the radiation doses delivered by the various imaging procedures commonly
      ordered in a rheumatology practice and to compare those doses with background
      radiation exposure in the United States. METHODS: The authors reviewed and
      compiled literature on radiation exposure from background radiation and
      diagnostic imaging procedures. The review included a Medline search through
      December 2003. RESULTS: Radiation doses from medical imaging procedures are so
      low that they do not have a clinically significant effect on mortality rates. In
      comparison to our normal daily exposures from naturally occurring background
      radiation and daily activities, the exposures from medical procedures are quite
      small. Moreover, the International Commission for Radiological Protection (ICRP)
      recommends that dose limits should not be applied to medical exposures in
      nonpregnant patients. Rather, the ICRP recommends that the medical exposure be
      justified and the protection be optimized so that the dose to the patient is as
      low as is compatible with the medical purpose. CONCLUSIONS AND RELEVANCE:
      Appropriate care of patients within the rheumatology practice frequently
      necessitates the use of imaging procedures that utilize ionizing radiation, such
      as radiographs, computed tomography scans, and bone densitometry. If ordered
      prudently, the benefits of these imaging procedures supersede the risks imposed
      by their radiation exposures.

PMID- 15846592
TI  - Health-related quality of life predicts future health care utilization and
      mortality in veterans with self-reported physician-diagnosed arthritis: the
      veterans arthritis quality of life study.
AB  - OBJECTIVE: To investigate whether health-related quality of life (HRQOL) measures
      predict health care utilization and mortality in a cohort of veterans with self
      reported physician-diagnosed arthritis. METHODS: A cohort of veterans from the
      Upper Midwest Veterans Integrated Service Network (VISN) was mailed a self
      administered questionnaire that was composed of the SF-36V (modified from SF-36
      for use in veterans) and questions regarding demographics, current smoking
      status, limitation of activities of daily living (ADLs), and preexisting
      physician-diagnosed medical conditions, including arthritis. Within subjects
      reporting physician-diagnosed arthritis, we analyzed the associations between the
      SF-36V component summary scales (physical and mental component summary, PCS and
      MCS, respectively) and the occurrence of any hospitalization, number of
      hospitalizations, number of outpatient visits, and mortality, for the year after
      survey administration, using multivariable regression analyses. RESULTS: Of
      34,440 survey responders who answered a question regarding arthritis, 18,464
      (58%) subjects reported physician-diagnosed arthritis. Arthritic patients in the
      lowest tertile of PCS scores had significantly higher odds of any hospitalization
      (Odds ratio (OR) 1.49, 95% confidence interval (CI) [1.25-1.76]) and mortality
      (OR 1.69, 95% CI [1.18-2.42]), and a significantly higher number of
      hospitalizations/year (Rate ratio (RR) 1.09, 95% CI [1.05-1.13]) and outpatient
      visits/year (RR 1.07, 95% CI [1.03-1.11]). Arthritic patients in the lowest
      tertile of MCS scores had significantly higher odds of any hospitalization (OR
      1.20, 95% CI [1.02-1.41]), mortality (OR 2.14, 95% CI [1.56-2.94]), and a
      significantly higher number of hospitalizations/year (RR 1.05, 95% CI [1.02
      1.09]) and outpatient visits/year (RR 1.07, 95% CI [1.03-1.11]). CONCLUSIONS:
      HRQOL, as assessed by the SF-36V, predicts future inpatient and outpatient health
      care utilization and mortality in veterans with self-report of physician
      diagnosed arthritis.

PMID- 15846593
TI  - Comparative study of postoperative and spontaneous pyogenic spondylodiscitis.
AB  - OBJECTIVES: Postoperative spondylodiscitis (POS) is poorly characterized, partly
      owing to its rarity. The aim of this prospective study was to compare the
      clinical, biological, bacteriological, and imaging features of postoperative and
      spontaneous spondylodiscitis (SS). METHODS: A multidisciplinary spondylodiscitis
      cohort follow-up study was conducted between February 1999 and June 2003 in a 500
      bed teaching hospital. All patients hospitalized in internal medicine,
      orthopedic, and neurosurgery wards with a culture-proven diagnosis of pyogenic
      spondylodiscitis were included. Clinical and bacteriological data were collected.
      All patients underwent computed tomography and/or magnetic resonance imaging of
      the spine. RESULTS: Sixteen patients had SS and 7 patients had POS. Patients with
      POS tended to be younger (52 versus 69 years), with less frequent underlying
      diseases (29 versus 75%) and a more prolonged interval between symptom onset and
      diagnosis (16 versus 3.4 weeks) than patients with SS. Blood cultures were
      positive in 14 and 81% of cases in the POS and SS groups, respectively, and
      invasive diagnostic procedures were necessary in 86% of patients with POS and 19%
      of patients with SS ( P = 0.005). Staphylococci were the more frequent isolates
      in both groups but were more frequently coagulase-negative in POS patients than
      in patients with SS ( P = 0.01). Vertebral edema tended to be more frequent in
      POS and was located more posteriorly than in SS ( P = 0.023). CONCLUSIONS: POS is
      associated with specific clinical, microbiological, and imaging features possibly
      related to pathophysiologic characteristics. Knowledge of these characteristics
      should help reduce the current delay in the diagnosis of POS.

PMID- 15846595
TI  - Developing promiscuous glycosidases for glycoside synthesis: residues W433 and
      E432 in Sulfolobus solfataricus beta-glycosidase are important glucoside- and
      galactoside-specificity determinants.
AB  - Two residues that have been implicated in determining the substrate specificity
      of the thermophilic beta-glycosidase from the archaeon Sulfolobus solfataricus
      (SsbetaG), a member of the glycosyl hydrolase family 1, have been mutated by site
      directed mutagenesis so as to create more versatile catalysts for carbohydrate
      chemistry. The wild-type and mutated sequences were expressed in E. coli with a
      His(7)-tag to allow one-step chromatographic purification. The E432C and W433C
      mutations removed key interactions with the OH-4 and OH-3 of the sugar
      substrates, thus reducing the discrimination of glucose, galactose and fucose
      with respect to other glycosides. This resulted in two glycosidases with greatly
      broadened substrate specificities. Observed changes include a 24-fold increase in
      Man:Gal activity and an 18-fold increase in GalA:Gal activity. This promiscuous
      substrate tolerance was further illustrated by the parallel synthesis of a beta
      glycoside library of glucose, galactose, xylose and mannose in one pot at 50
      degrees C, in organic solvent. The synthetic potential of the catalysts was
      further evaluated through alkyl glycoside transglycosylation yields, including
      the first examples of synthesis of beta-mannosides and beta-xylosides with
      SsbetaG.

PMID- 15846598
TI  - Electroconvulsive therapy for schizophrenia.
AB  - BACKGROUND: Electroconvulsive therapy (ECT) involves the induction of a seizure
      for therapeutic purposes by the administration of a variable frequency electrical
      stimulus shock via electrodes applied to the scalp. The effects of its use in
      people with schizophrenia are unclear. OBJECTIVES: To determine whether
      electroconvulsive therapy (ECT) results in clinically meaningful benefit with
      regard to global improvement, hospitalisation, changes in mental state, behaviour
      and functioning for people with schizophrenia, and to determine whether
      variations in the practical administration of ECT influences outcome. SEARCH
      STRATEGY: We undertook electronic searches of Biological Abstracts (1982-1996),
      EMBASE (1980-1996), MEDLINE (1966-2004), PsycLIT (1974-1996),SCISEARCH (1996) and
      the Cochrane Schizophrenia Group's Register (July 2004). We also inspected the
      references of all identified studies and contacted relevant authors. SELECTION
      CRITERIA: We included all randomised controlled clinical trials that compared ECT
      with placebo, 'sham ECT', non-pharmacological interventions and antipsychotics
      and different schedules and methods of administration of ECT for people with
      schizophrenia, schizoaffective disorder or chronic mental disorder. DATA
      COLLECTION AND ANALYSIS: Working independently, we selected and critically
      appraised studies, extracted data and analysed on an intention-to-treat basis.
      Where possible and appropriate we calculated risk ratios (RR) and their 95%
      confidence intervals (CI) with the number needed to treat (NNT). For continuous
      data Weighted Mean Differences (WMD) were calculated. We presented scale data for
      only those tools that had attained pre-specified levels of quality. We also
      undertook tests for heterogeneity and publication bias. MAIN RESULTS: This review
      includes 26 trials with 50 reports. When ECT is compared with placebo or sham
      ECT, more people improved in the real ECT group (n=392, 10 RCTs, RR 0.76 random
      CI 0.59 to 0.98, NNT 6 CI 4 to 12) and though data were heterogeneous (chi-square
      17.49 df=9 P=0.04), its impact on variability of data was not substantial (I
      squared 48.5%). There was a suggestion that ECT resulted in less relapses in the
      short term than sham ECT (n=47, 2 RCTs, RR fixed 0.26 CI 0.03 to 2.2), and a
      greater likelihood of being discharged from hospital (n=98, 1 RCT, RR fixed 0.59,
      CI 0.34 to 1.01). There is no evidence that this early advantage for ECT is
      maintained over the medium to long term. People treated with ECT did not drop out
      of treatment earlier than those treated with sham ECT (n=495, 14 RCTs, RR fixed
      0.71 CI 0.33 to 1.52, I-squared 0%). Very limited data indicated that visual
      memory might decline after ECT compared with sham ECT (n=24, 1 RCT, WMD -14.0 CI 
      23 to -5); the results of verbal memory tests were equivocal. When ECT is
      directly compared with antipsychotic drug treatments (total n=443, 10 RCTs)
      results favour the medication group (n=175, 3 RCTs, RR fixed 'not improved at the
      end of ECT course' 2.18 CI 1.31 to 3.63). Limited evidence suggests that ECT
      combined with antipsychotic drugs results in greater improvement in mental state
      (n= 40, 1 RCT, WMD, Brief Psychiatric Rating Scale -3.9 CI - 2.28 to -5.52) than
      with antipsychotic drugs alone. One small study suggested more memory impairment
      after a course of ECT combined with antipsychotics than with antipsychotics alone
      (n=20, MD serial numbers and picture recall -4.90 CI -0.78 to -9.02), though this
      proved transient. When continuation ECT was added to antipsychotic drugs, the
      combination was superior to the use of antipsychotics alone (n=30, WMD Global
      Assessment of Functioning 19.06 CI 9.65 to 28.47), or CECT alone (n=30, WMD 
      20.30 CI -11.48 to -29.12). Unilateral and bilateral ECT were equally effective
      in terms of global improvement (n=78, 2 RCTs, RR fixed 'not improved at end of
      course of ECT' 0.79 CI 0.45 to 1.39). One trial showed a significant advantage
      for 20 treatments over 12 treatments for numbers globally improved at the end of
      the ECT course (n=43, RR fixed 2.53 CI 1.13 to 5.66). AUTHORS' CONCLUSIONS: The
      evidence in this review suggests that ECT, combined with treatment with
      antipsychotic drugs, may be considered an option for people with schizophrenia,
      particularly when rapid global improvement and reduction of symptoms is desired.
      This is also the case for those with schizophrenia who show limited response to
      medication alone. Even though this initial beneficial effect may not last beyond
      the short term, there is no clear evidence to refute its use for people with
      schizophrenia. The research base for the use of ECT in people with schizophrenia
      continues to expand, but even after more than five decades of clinical use, there
      remain many unanswered questions regarding its role in the management of people
      with schizophrenia.

PMID- 15846599
TI  - Family therapy for chronic asthma in children.
AB  - BACKGROUND: Psychosocial and emotional factors are important in childhood asthma.
      Nevertheless, drug therapy alone continues to be the main treatment. Treatment
      programmes that include behavioural or psychological interventions have been
      developed to improve disturbed family relations in the families of children with
      severe asthma. These approaches have been extended to examine the efficacy of
      family therapy to treat childhood asthma in a wider group of patients. This
      review systematically examines these studies. OBJECTIVES: Recognition that asthma
      can be associated with emotional disturbances has led to the investigation of the
      role of family therapy in reducing the symptoms and impact of asthma in children.
      The objective of this review was to assess the effects of family therapy as an
      adjunct to medication for the treatment of asthma in children. SEARCH STRATEGY:
      We searched the Cochrane Airways Group trials register, Psychlit and Psychinfo.
      Searches are current as of January 2005. SELECTION CRITERIA: Randomised trials
      comparing children undergoing systematic therapy focusing on the family in
      conjunction with asthma medication, with children taking asthma medication only.
      DATA COLLECTION AND ANALYSIS: Two reviewers assessed the studies for inclusion in
      the review. MAIN RESULTS: Two trials with a total of 55 children were included.
      It was not possible to combine the findings of these two studies because of
      differences in outcome measures used. In one study, gas volume, peak expiratory
      flow rate and daytime wheeze showed improvement in family therapy patients
      compared to controls. In the other study, there was an improvement in overall
      clinical assessment and number of functionally impaired days in the patients
      receiving family therapy. There was no difference in forced expiratory volume or
      medication use in both studies. AUTHORS' CONCLUSIONS: There is some indication
      that family therapy may be a useful adjunct to medication for children with
      asthma. This conclusion is limited by small study sizes and lack of
      standardisation in the choice of outcome measures.

PMID- 15846600
TI  - Low-molecular-weight heparins or heparinoids versus standard unfractionated
      heparin for acute ischaemic stroke.
AB  - BACKGROUND: Low-molecular-weight heparins and heparinoids are anticoagulants that
      may be associated with lower risks of haemorrhage and more powerful
      antithrombotic (anti-clotting) effects than standard unfractionated heparin.
      OBJECTIVES: The objective of this review was to compare the effects of low
      molecular-weight heparins or heparinoids with those of unfractionated heparin in
      people with acute, confirmed or presumed, ischaemic stroke (sudden blockage of an
      artery carrying blood to the brain). SEARCH STRATEGY: We searched the Cochrane
      Stroke Group trials register (last searched November 2003). In addition we
      searched the Cochrane Central Register of Controlled Trials (The Cochrane Library
      Issue 4, 2003), MEDLINE (1966 to October 2003) and EMBASE (1980 to October 2003).
      For previous versions of this review we searched MedStrategy (1995) and also
      contacted pharmaceutical companies. SELECTION CRITERIA: Randomised trials
      comparing heparinoids or low-molecular-weight heparins with standard
      unfractionated heparin in people with acute ischaemic stroke. Only trials where
      treatment was started within 14 days of stroke onset were included. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently selected studies for
      inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Six
      trials involving 740 people were included. Four trials compared a heparinoid
      (danaparoid), one trial compared a low-molecular-weight heparin (enoxaparin), and
      one trial compared an unspecified low-molecular-weight heparin with standard
      unfractionated heparin. Allocation a to low-molecular-weight heparin or
      heparinoid was associated with a significant reduction in the odds of deep vein
      thrombosis (Peto odds ratio 0.52, 95% confidence interval 0.56 to 0.79). However,
      the number of more major events (pulmonary embolism, death, intra-cranial or
      extra-cranial haemorrhage) was too small to provide a reliable estimate of more
      important benefits and risks. No information was reported for recurrent stroke or
      functional outcome. AUTHORS' CONCLUSIONS: Treatment with a low-molecular-weight
      heparin or heparinoid after acute ischaemic stroke appears to decrease the
      occurrence of deep vein thrombosis compared to standard unfractionated heparin,
      but there are too few data to provide reliable information on their effects on
      other important outcomes, including death and intracranial haemorrhage.

PMID- 15846601
TI  - Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances
      associated with chronic cerebral disorders in the elderly.
AB  - BACKGROUND: CDP-choline (cytidine 5'-diphosphocholine) is a precursor essential
      for the synthesis of phosphatidylcholine, one of the cell membrane components
      that is degraded during cerebral ischaemia to free fatty acids and free radicals.
      Animal studies suggest that CDP-choline may protect cell membranes by
      accelerating resynthesis of phospholipids. CDP-choline may also attenuate the
      progression of ischaemic cell damage by suppressing the release of free fatty
      acids. CDP-choline is the endogenous compound normally produced by the organism.
      When the same substance is introduced as a drug it can be called citicoline.CDP
      choline is mainly used in the treatment of disorders of a cerebrovascular nature.
      The many years of its presence in the clinical field have caused an evolution in
      dosage, method of administration, and selection criteria of patients to whom the
      treatments were given. Modalities of the clinical studies, including length of
      observation, severity of disturbance, and methodology of evaluation of the
      results were also heterogeneous. In spite of uncertainties about its efficacy due
      to these complexities, CDP-choline is a frequently prescribed drug for cognitive
      impairment in several European countries, especially when the clinical picture is
      predominantly one of cerebrovascular disease, hence the need for this review. Due
      to its effects on the adrenergic and dopaminergic activity of the CNS, CDP
      choline has also been used as an adjuvant in the treatment of Parkinson's
      disease. OBJECTIVES: To assess the efficacy of CDP-choline
      (cytidinediphosphocholine) in the treatment of cognitive, emotional, and
      behavioural deficits associated with chronic cerebral disorders in the elderly.
      SEARCH STRATEGY: The trials were identified from a last updated search of the
      Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on
      22 April 2004 using the terms CDP-choline, CDP, citicoline, cytidine diphosphate
      choline or diphosphocholine. The Register contains records from all major health
      care databases and many ongoing trials databases and is updated regularly.
      SELECTION CRITERIA: All relevant unconfounded, double-blind, placebo-controlled,
      randomized trials of CDP-choline for cognitive impairment due to chronic cerebral
      disorders were considered for inclusion in the review. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently reviewed the included studies, extracted
      the data, and pooled it when appropriate and possible. The pooled odd ratios (95%
      Confidence Interval (CI)) or the average differences (95% CI) were estimated. No
      intention-to-treat data were available from the studies included. MAIN RESULTS:
      Fourteen studies were included in this review. Some of the included studies did
      not present numerical data suitable for analysis. Description of participants
      varied over the years and by type of disorders and severity, and ranged from aged
      individuals with subjective memory disorders to patients with Vascular Cognitive
      Impairment (mild to moderate), Vascular Dementia or Senile Dementia (mild to
      moderate). Seven of the included studies observed the subjects for a period
      between 20 to 30 days, one study was of 6 weeks duration, four studies used
      periods extending over 2 and 3 months, one study observed continuous
      administration over 3 months and one study was prolonged, with 12 months of
      observation. The studies were heterogeneous in dose, modalities of
      administration, inclusion criteria for subjects, and outcome measures. Results
      were reported for the domains of attention, memory testing, behavioural rating
      scales, global clinical impression and tolerability. There was no evidence of a
      beneficial effect of CDP-choline on attention. There was evidence of benefit of
      CDP-choline on memory function and behaviour. The drug was well tolerated.
      AUTHORS' CONCLUSIONS: There was some evidence that CDP-choline has a positive
      effect on memory and behaviour in at least the short to medium term. The evidence
      of benefit from global impression was stronger, but is still limited by the
      duration of the studies. Further research with CDP-choline should focus on longer
      term studies in subjects who have been diagnosed with currently accepted
      standardised criteria, especially Vascular Mild Cognitive Impairment (VaMCI) or
      vascular dementia.

PMID- 15846602
TI  - Cyclosporine for induction of remission in Crohn's disease.
AB  - BACKGROUND: Cyclosporine was first found to be an effective and well-tolerated
      immunosuppressive agent in organ transplant recipients, and subsequently in
      several autoimmune diseases. It was reported in open studies that cyclosporine is
      effective for induction of remission in Crohn's disease. Four randomized
      controlled trials have been performed to determine whether the results observed
      in these open studies were valid. This systematic review summarizes the evidence
      on the use of oral cyclosporine for the induction of remission in Crohn's
      disease. OBJECTIVES: To evaluate the effectiveness of oral cyclosporine for
      induction of remission in patients with active Crohn's disease in the presence
      and absence of concomitant steroid therapy. Secondary objectives were to evaluate
      clinical response rates and adverse events associated with cyclosporine. SEARCH
      STRATEGY: Computer-assisted searches of the on-line bibliographic databases
      MEDLINE and EMBASE were performed to identify potentially relevant publications
      between 1980 and July 2004. The MeSH terms "Crohn Disease" or "Inflammatory Bowel
      disease" and "Cyclosporin" (exploded) were used to perform key word searches of
      the databases. Manual searches of reference lists from potentially relevant
      papers were performed in order to identify additional studies that may have been
      missed. Abstracts from major gastroenterological meetings, The Cochrane Central
      Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease Group
      Specialized Trials Register were also searched for relevant studies. Appropriate
      officials at Sandoz Corporation were contacted to seek information on any
      unpublished trials. SELECTION CRITERIA: Prospective, randomized, double-blinded,
      placebo-controlled trials of parallel design with treatment duration of a minimum
      12 weeks comparing oral cyclosporine therapy with placebo for treatment of
      patients with active Crohn's disease were eligible for inclusion. DATA COLLECTION
      AND ANALYSIS: All data were analyzed on an intention-to-treat basis. Data were
      extracted from the original research articles and converted into 2x2 tables
      (cyclosporine vs. placebo). Where available, individual 2x2 tables for strata
      within studies were also used. Heterogeneity was assessed using the chi-square
      test (p < 0.10 was regarded as statistically significant). For non-pooled data, p
      values were derived using the chi-square test. For pooled data, summary test
      statistics were derived using the Peto odds ratio and 95% confidence intervals. A
      fixed effects model was used for pooling of data. For continuous data, summary
      test statistics were derived using the weighted mean difference and 95%
      confidence intervals. The definitions of treatment success, remission and
      clinical improvement were set by the authors of each paper, and the data were
      combined for analysis only if these definitions were sufficiently similar. MAIN
      RESULTS: Brynskov 1989a found that patients receiving high dose cyclosporine
      (median 7.6 mg/kg/day) had statistically significant clinical improvement at 12
      weeks compared to placebo patients. None of the other studies found any
      statistically significant benefit for clinical improvement or induction of
      remission for low dose cyclosporine treatment (5 mg/kg/day) used by itself or in
      combination with corticosteroids compared to placebo. Cyclosporine was associated
      with a significantly higher proportion of adverse events and withdrawals due to
      adverse events relative to placebo. AUTHORS' CONCLUSIONS: Brynskov 1989a enrolled
      a small number of patients and the modified clinical grading scale used in the
      study has not been validated in other studies. Furthermore, statistically
      significant clinical improvement does not imply induction of clinical remission.
      Indeed, Brynskov 1989a found no statistically significant differences in the mean
      Crohn's Disease Activity Index score at 12 weeks indicating that cyclosporine was
      no more effective than placebo for induction of remission in Crohn's disease. The
      results of this review demonstrate that low dose (5 mg/kg/day) oral cyclosporine
      is not effective for the induction of remission in Crohn's disease. Patients
      treated with low dose oral cyclosporine are more likely than placebo treated
      patients to experience adverse events including renal dysfunction. The use of low
      dose oral cyclosporine for the treatment of chronic active Crohn's disease does
      not appear to be justified. Oral dosing at higher levels or parenteral
      administration of cyclosporine have not been adequately evaluated in controlled
      clinical trials. Higher doses of cyclosporine are not likely to be useful for the
      long-term management of Crohn's disease because of the risk of nephrotoxicity and
      the availability of other proven interventions.

PMID- 15846603
TI  - Medicinal and injection therapies for mechanical neck disorders.
AB  - BACKGROUND: Medicinal therapies and injections are commonly recommended for neck
      pain, yet controversy persists over their effectiveness. OBJECTIVES: To determine
      the effect of medicines and injections on pain, function/disability, patient
      satisfaction and range of motion in participants with mechanical neck disorders
      (MND). SEARCH STRATEGY: We searched CENTRAL (Issue 4, 2002), and MEDLINE, EMBASE,
      MANTIS, CINHAL from their start to March 2003. We scrutinized reference lists for
      other trials. SELECTION CRITERIA: We included randomized controlled trials with
      adults with MND, with or without associated headache or radicular findings. We
      considered medicinal and injection therapies, regardless of route of
      administration. DATA COLLECTION AND ANALYSIS: Two authors independently selected
      articles, abstracted data and assessed methodological quality using the Jadad
      criteria. Consensus was used to resolve disagreements. When clinical
      heterogeneity was absent, we combined studies using random-effects meta-analysis
      models. MAIN RESULTS: We found 32 trials that examined the effects of oral
      NSAIDs, psychotropic agents, injections of steroids, and anaesthetic agents.
      Overall, methodological quality had a mean of 3.2/5 on the Jadad Scale. For acute
      whiplash, administering intravenous methylprednisolone within eight hours reduced
      pain at one week, and sick leave but not pain at six months compared to placebo.
      For chronic MND at short-term follow-up, intramuscular injection of lidocaine was
      superior to placebo or dry needling, but similar to ultrasound. In chronic MND
      with radicular findings, epidural methylprednisolone and lidocaine reduced neck
      pain and improved function at one-year follow-up compared to the intramuscular
      route. In subacute/chronic MND, we found conflicting evidence of pain reduction
      for oral psychotropic agents compared to placebo or control. Single trials of
      eperison hydrochloride and tetrazepam showed positive results. Results for
      cyclobenzaprine were mixed. Diazepam did not show benefit. Other treatments
      including NSAIDS and nerve blocks had unclear or limited evidence of benefit. In
      participants with chronic MND with or without radicular findings or headache,
      there was moderate evidence from five high quality trials showing that Botox A
      intramuscular injections were not better than saline in improving pain (pooled
      SMD: -0.39 (95%CI: -1.25 to 0.47), disability or global perceived effect.
      AUTHORS' CONCLUSIONS: Intra-muscular injection of lidocaine for chronic MND and
      intravenous injection of methylprednisolone for acute whiplash were effective
      treatments. There was limited evidence of effectiveness of epidural injection of
      methylprednisolone and lidocaine for chronic MND with radicular findings. Oral
      psychotropic agents had mixed results. There was moderate evidence that Botox A
      intramuscular injections for chronic MND were no better than saline. Other
      medications, including NSAIDs, had contradictory or limited evidence of
      effectiveness.

PMID- 15846604
TI  - Services for reducing duration of hospital care for acute stroke patients.
AB  - BACKGROUND: Stroke patients conventionally receive a substantial part of their
      rehabilitation in hospital. Services have now been developed which offer patients
      in hospital an early discharge with rehabilitation at home (early supported
      discharge (ESD)). OBJECTIVES: To establish the effects and costs of ESD services
      compared with conventional services. SEARCH STRATEGY: We searched the Cochrane
      Stroke Group's trials register (last searched August 2004) and obtained further
      information from individual trialists. SELECTION CRITERIA: Randomised controlled
      trials recruiting stroke patients in hospital to receive either conventional care
      or any service intervention which has provided rehabilitation and support in a
      community setting with an aim of reducing the duration of hospital care. DATA
      COLLECTION AND ANALYSIS: Two reviewers scrutinised trials and categorised them on
      their eligibility. Standardised individual patient data was then sought from the
      primary trialists. Results were analysed for all trials and for subgroups of
      patients and services; in particular whether the intervention was provided by a
      co-ordinated multidisciplinary team (co-ordinated ESD team) or not. MAIN RESULTS:
      Outcome data are currently available for 11 trials (1597 patients). Patients
      tended to be a selected elderly group with moderate disability. The ESD group
      showed significant reductions (P < 0.0001) in the length of hospital stay
      equivalent to approximately 8 days. Overall, the odds ratios (OR) (95% confidence
      interval (CI)) for death, death or institutionalisation, death or dependency at
      the end of scheduled follow up were OR 0.90, 95% CI 0.64 to 1.27, P = 0.56, OR
      0.74, 95% CI 0.56 to 0.96, P = 0.02 and OR 0.79, 95% CI 0.64 to 0.97, P = 0.02,
      respectively. The greatest benefits were seen in the trials evaluating a co
      ordinated ESD team and in stroke patients with mild-moderate disability.
      Improvements were also seen in patients' extended activities of daily living
      scores (standardised mean difference 0.12, 95% CI 0.00 to 0.25, P = 0.05) and
      satisfaction with services (OR 1.60, 95% CI 1.08 to 2.38, P = 0.02) but no
      statistically significant differences were seen in carers' subjective health
      status, mood or satisfaction with services. AUTHORS' CONCLUSIONS: Appropriately
      resourced ESD services provided for a selected group of stroke patients can
      reduce long term dependency and admission to institutional care as well as
      reducing the length of hospital stay. No adverse impact was observed on the mood
      or subjective health status of patients or carers.

PMID- 15846605
TI  - St John's wort for depression.
AB  - BACKGROUND: Extracts of the plant Hypericum perforatum L. (popularly called St.
      John's wort) have been used in folk medicine for a long time for a range of
      indications including depressive disorders. OBJECTIVES: To investigate whether
      extracts of hypericum are more effective than placebo and as effective as
      standard antidepressants in the treatment of depressive disorders in adults; and
      whether they have have less adverse effects than standard antidepressant drugs.
      SEARCH STRATEGY: Trials were searched in computerized databases (Cochrane
      Collaboration Depression, Anxiety & Neurosis Group Clinical Trials Registers;
      PubMed); by checking bibliographies of pertinent articles; and by contacting
      manufacturers and researchers. SELECTION CRITERIA: Trials were included if they:
      (1) were randomized and double-blind; (2) included patients with depressive
      disorders; (3) compared extracts of St. John's wort with placebo or standard
      antidepressants; and (4) included clinical outcomes such as scales assessing
      depressive symptoms. DATA COLLECTION AND ANALYSIS: Information on patients,
      interventions, outcomes and results was extracted by at least two independent
      reviewers using a standard form. The main outcome measure for comparing the
      effectiveness of hypericum with placebo and standard antidepressants was the
      responder rate ratio (responder rate in treatment group/responder rate in control
      group). The main outcome measure for adverse effects was the number of patients
      dropping out for adverse effects. MAIN RESULTS: A total of 37 trials, including
      26 comparisons with placebo and 14 comparisons with synthetic standard
      antidepressants, met the inclusion criteria. Results of placebo-controlled trials
      showed marked heterogeneity. In trials restricted to patients with major
      depression, the combined response rate ratio (RR) for hypericum extracts compared
      with placebo from six larger trials was 1.15 (95% confidence interval (CI), 1.02
      1.29) and from six smaller trials was 2.06 (95% CI, 1.65 to 2.59). In trials not
      restricted to patients with major depression, the RR from six larger trials was
      1.71 (95% CI, 1.40-2.09) and from five smaller trials was 6.13 (95% CI, 3.63 to
      10.38). Trials comparing hypericum extracts and standard antidepressants were
      statistically homogeneous. Compared with selective serotonin reuptake inhibitors
      (SSRIs) and tri- or tetracyclic antidepressants, respectively, RRs were 0.98 (95%
      CI, 0.85-1.12; six trials) and 1.03 (95% CI, 0.93-1.14; seven trials). Patients
      given hypericum extracts dropped out of trials due to adverse effects less
      frequently than those given older antidepressants (Odds ratio (OR) 0.25; 95% CI,
      0.14-0.45); such comparisons were in the same direction, but not statistically
      significantly different, between hypericum extracts and SSRIs (OR 0.60, 95% CI,
      0.31-1.15). AUTHORS' CONCLUSIONS: Current evidence regarding hypericum extracts
      is inconsistent and confusing. In patients who meet criteria for major
      depression, several recent placebo-controlled trials suggest that the tested
      hypericum extracts have minimal beneficial effects while other trials suggest
      that hypericum and standard antidepressants have similar beneficial effects. As
      the preparations available on the market might vary considerably in their
      pharmaceutical quality, the results of this review apply only to the products
      tested in the included studies.

PMID- 15846606
TI  - Interventions for preventing and treating stress fractures and stress reactions
      of bone of the lower limbs in young adults.
AB  - BACKGROUND: Stress reaction in bone, which may proceed to a fracture, is a
      significant problem in military recruits and in athletes, particularly long
      distance runners. OBJECTIVES: To evaluate the evidence from randomised controlled
      trials of interventions for prevention or management of lower-limb stress
      fractures and stress reactions of bone in active young adults. SEARCH STRATEGY:
      We searched the Cochrane Musculoskeletal Injuries Group Specialised Register
      (April 2004), the Cochrane Central Register of Controlled Trials (The Cochrane
      Library Issue 1, 2004), MEDLINE (1966 to September week 1, 2004), EMBASE, CINAHL,
      Index to UK Theses, reference lists of relevant articles and contacted trialists.
      SELECTION CRITERIA: Any randomised or quasi-randomised trials evaluating
      interventions for preventing or treating lower limb stress reactions of bone or
      stress fractures in active young adults. DATA COLLECTION AND ANALYSIS: We
      independently selected trials for inclusion, assessed trial quality and extracted
      data. Only limited data pooling was undertaken. MAIN RESULTS: We included 16
      trials. All 13 prevention trials involved military recruits undergoing training.
      Participants of two of the three treatment trials were military personnel. Ten
      prevention trials tested the effects of various foot inserts and other footwear
      modifications. While pooling of data was not possible, the four trials evaluating
      the use of "shock-absorbing" boot inserts versus control found fewer stress
      injuries of the bone in their intervention groups. However, the only trial
      showing a significant benefit lacked important information about trial design. A
      key issue in several trials was the acceptability, in terms of practicality and
      comfort, of the boot inserts. Two cluster-randomised prevention trials found no
      significant effect of leg muscle stretching during warm up before exercise.
      Pooled data from three small but very different trials testing the use of
      pneumatic braces in the rehabilitation of tibial stress fractures showed a
      significant reduction in the time to recommencing full activity (weighted mean
      difference -33.39 days, 95% confidence interval -44.18 to -22.59 days). These
      results were highly heterogeneous (I squared = 90%), which is likely to reflect
      the underlying differences of the trials, including differences in the control
      group interventions and definitions of outcomes. AUTHORS' CONCLUSIONS: The use of
      shock absorbing inserts in footwear probably reduces the incidence of stress
      fractures in military personnel. There is insufficient evidence to determine the
      best design of such inserts but comfort and tolerability should be considered.
      Rehabilitation after tibial stress fracture may be aided by the use of pneumatic
      bracing but more evidence is required to confirm this.

PMID- 15846607
TI  - Percutaneous transluminal angioplasty and stenting for vertebral artery stenosis.
AB  - BACKGROUND: Surgery for vertebral artery stenosis is technically difficult,
      potentially hazardous and is not considered in most centres. There is growing
      evidence from case series that vertebral artery stenosis may be treated
      endovascularly by percutaneous transluminal angioplasty and stenting. This may be
      a feasible alternative to surgery to relieve symptoms caused by significant
      stenosis. OBJECTIVES: The objective of this review was to assess the safety and
      efficacy of vertebral artery percutaneous transluminal angioplasty, with or
      without stenting, combined with medical care, compared to medical care alone, in
      patients with vertebral artery stenosis. SEARCH STRATEGY: We searched the
      Cochrane Stroke Group's trials register (last searched 28 July 2004). In addition
      we searched the following bibliographic databases: Cochrane Central Register of
      Controlled Trials (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 to July
      2004), EMBASE (1980 to July 2004), and Science Citation Index (1981 to July
      2004). We also contacted researchers in the field, and balloon catheter and stent
      manufacturers. SELECTION CRITERIA: We selected randomised trials of endovascular
      treatment of vertebral artery stenosis combined with best medical therapy,
      compared with best medical therapy alone, in patients with symptomatic or
      asymptomatic vertebral artery stenosis. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently applied the inclusion criteria, extracted data and
      assessed trial quality. MAIN RESULTS: One completed randomised trial was found.
      In one subgroup of this trial, 16 patients with symptomatic severe vertebral
      artery stenosis were randomised to endovascular treatment (n = 8) or medical
      treatment alone (n = 8). There were no strokes in any arterial territory or
      deaths from any cause in either group within 30 days of treatment (endovascular
      group) or 30 days of randomisation (medical group). In the endovascular group,
      two patients had a posterior circulation TIA at the time of the procedure. In the
      endovascular group, the mean vessel stenosis at follow up was 47% (range 0% to
      80%). Patients were followed up for a mean of 4.5 years in the endovascular group
      and 4.9 years in the medical group. There were no further vertebrobasilar
      territory strokes in either group for the duration of follow up. Morbidity and
      mortality was related to carotid and coronary artery disease in this study.
      AUTHORS' CONCLUSIONS: There is currently insufficient evidence to assess the
      effects of percutaneous transluminal angioplasty with or without stenting or
      primary stenting for vertebral artery stenosis.

PMID- 15846608
TI  - Nutritional supplementation for stable chronic obstructive pulmonary disease.
AB  - BACKGROUND: Low body weight in patients with chronic obstructive pulmonary
      disease (COPD) is associated with an impaired pulmonary status, reduced
      diaphragmatic mass, lower exercise capacity and higher mortality rate when
      compared to adequately nourished individuals with this disease. Nutritional
      support may therefore be a useful part of their comprehensive care. OBJECTIVES:
      To conduct a systematic review of randomised controlled trials (RCTs) to clarify
      whether nutritional supplementation (caloric supplementation for at least 2
      weeks) improved anthropometric measures, pulmonary function, respiratory muscle
      strength and functional exercise capacity in patients with stable COPD. SEARCH
      STRATEGY: Randomized controlled trials (RCTs) were identified from the Cochrane
      Airways Group register of RCTs, a hand-search of abstracts presented at
      international meetings and consultation with experts. Searches are current as of
      March 2004. SELECTION CRITERIA: Two reviewers independently selected trials for
      inclusion, assessed quality and extracted the data. DATA COLLECTION AND ANALYSIS:
      Within each trial and for each outcome, we calculated an effect size. The effect
      sizes were then pooled by a random-effects model. Homogeneity among the effect
      sizes was also tested. MAIN RESULTS: Eleven studies recruiting 352 participants
      met the inclusion criteria. Eight papers were considered as high quality. Two
      studies were double-blinded. For each of the outcomes studied, the effect of
      nutritional support was small: the 95% confidence intervals around the pooled
      effect sizes all included zero. The effect of nutritional support was homogeneous
      across studies. AUTHORS' CONCLUSIONS: Nutritional support had no significant
      effect on anthropometric measures, lung function or exercise capacity in patients
      with stable COPD.

PMID- 15846609
TI  - Manual therapy for asthma.
AB  - BACKGROUND: A variety of manual therapies with similar postulated biologic
      mechanisms of action are commonly used to treat patients with asthma. Manual
      therapy practitioners are also varied, including physiotherapists, respiratory
      therapists, chiropractic and osteopathic physicians. A systematic review across
      disciplines is warranted. OBJECTIVES: To evaluate the evidence for the effects of
      manual therapies for treatment of patients with bronchial asthma. SEARCH
      STRATEGY: We searched for trials in computerized general (EMBASE, CINAHL and
      MEDLINE) and specialized databases (Cochrane Complementary Medicine Field,
      Cochrane Rehabilitation Field, Index to Chiropractic Literature (ICL), and
      Manual, Alternative and Natural Therapy (MANTIS)). In addition, we assessed
      bibliographies from included studies, and contacted authors of known studies for
      additional information about published and unpublished trials. Date of most
      recent search: August 2004. SELECTION CRITERIA: Trials were included if they: (1)
      were randomised; (2) included asthmatic children or adults; (3) examined one or
      more types of manual therapy; and (4) included clinical outcomes with observation
      periods of at least two weeks. DATA COLLECTION AND ANALYSIS: All three reviewers
      independently extracted data and assessed trial quality using a standard form.
      MAIN RESULTS: From 473 unique citations, 68 full text articles were retrieved and
      evaluated, which resulted in nine citations to three RCTs (156 patients) suitable
      for inclusion. Trials could not be pooled statistically because studies that
      addressed similar interventions used disparate patient groups or outcomes. The
      methodological quality of one of two trials examining chiropractic manipulation
      was good and neither trial found significant differences between chiropractic
      spinal manipulation and a sham manoeuvre on any of the outcomes measured. One
      small trial compared massage therapy with a relaxation control group and found
      significant differences in many of the lung function measures obtained. However,
      this trial had poor reporting characteristics and the data have yet to be
      confirmed. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the
      use of manual therapies for patients with asthma. There is a need to conduct
      adequately-sized RCTs that examine the effects of manual therapies on clinically
      relevant outcomes. Future trials should maintain observer blinding for outcome
      assessments, and report on the costs of care and adverse events. Currently, there
      is insufficient evidence to support or refute the use of manual therapy for
      patients with asthma.

PMID- 15846610
TI  - Group behaviour therapy programmes for smoking cessation.
AB  - BACKGROUND: Group therapy offers individuals the opportunity to learn behavioural
      techniques for smoking cessation, and to provide each other with mutual support.
      OBJECTIVES: We aimed to determine the effects of smoking cessation programmes
      delivered in a group format compared to self-help materials, or to no
      intervention; to compare the effectiveness of group therapy and individual
      counselling; and to determine the effect of adding group therapy to advice from a
      health professional or to nicotine replacement. We also aimed to determine
      whether specific components increased the effectiveness of group therapy. We
      aimed to determine the rate at which offers of group therapy are taken up. SEARCH
      STRATEGY: We searched the Cochrane Tobacco Addiction Group Trials Register, with
      additional searches of MEDLINE and PsycINFO, including the terms behavior
      therapy, cognitive therapy, psychotherapy or group therapy, in January 2005.
      SELECTION CRITERIA: We considered randomized trials that compared group therapy
      with self help, individual counselling, another intervention or no intervention
      (including usual care or a waiting list control). We also considered trials that
      compared more than one group programme. We included those trials with a minimum
      of two group meetings, and follow up of smoking status at least six months after
      the start of the programme. We excluded trials in which group therapy was
      provided to both active therapy and placebo arms of trials of pharmacotherapies,
      unless they had a factorial design. DATA COLLECTION AND ANALYSIS: We extracted
      data in duplicate on the participants, the interventions provided to the groups
      and the controls, including programme length, intensity and main components, the
      outcome measures, method of randomization, and completeness of follow up. The
      main outcome measure was abstinence from smoking after at least six months follow
      up in patients smoking at baseline. We used the most rigorous definition of
      abstinence in each trial, and biochemically validated rates where available.
      Subjects lost to follow up were analyzed as continuing smokers. Where possible,
      we performed meta-analysis using a fixed-effects (Mantel-Haenszel) model. MAIN
      RESULTS: A total of 55 trials met inclusion criteria for one or more of the
      comparisons in the review. Sixteen studies compared a group programme with a self
      help programme. There was an increase in cessation with the use of a group
      programme (N = 4395, odds ratio (OR) 2.04, 95% confidence interval (CI) 1.60 to
      2.60). Group programmes were more effective than no intervention controls (seven
      trials, N = 815, OR 2.17, 95% CI 1.37 to 3.45). There was no evidence that group
      therapy was more effective than a similar intensity of individual counselling.
      There was limited evidence that the addition of group therapy to other forms of
      treatment, such as advice from a health professional or nicotine replacement,
      produced extra benefit. There was variation in the extent to which those offered
      group therapy accepted the treatment. There was limited evidence that programmes
      which included components for increasing cognitive and behavioural skills and
      avoiding relapse were more effective than same length or shorter programmes
      without these components. This analysis was sensitive to the way in which one
      study with multiple conditions was included. We did not find an effect of
      manipulating the social interactions between participants in a group programme on
      outcome. AUTHORS' CONCLUSIONS: Group therapy is better for helping people stop
      smoking than self help, and other less intensive interventions. There is not
      enough evidence to evaluate whether groups are more effective, or cost-effective,
      than intensive individual counselling. There is not enough evidence to support
      the use of particular psychological components in a programme beyond the support
      and skills training normally included.

PMID- 15846611
TI  - Hands and knees posture in late pregnancy or labour for fetal malposition
      (lateral or posterior).
AB  - BACKGROUND: Lateral and posterior position of the baby's head (the back of the
      baby's head facing to the side or the mother's back) may be associated with more
      painful, prolonged or obstructed labour and difficult delivery. It is possible
      that certain positions adopted by the mother may influence the baby's position.
      OBJECTIVES: The objective of this review is to assess the effects of adopting a
      hands and knees maternal posture in late pregnancy or during labour when the
      presenting part of the fetus is in a lateral or posterior position, compared with
      no intervention. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group Trials Register (November 2004) and the Cochrane Central
      Register of Controlled Trials (The Cochrane Library, Issue 4, 2004). SELECTION
      CRITERIA: Randomised trials of hands and knees maternal posture compared to other
      postures or controls. DATA COLLECTION AND ANALYSIS: Both review authors assessed
      trial eligibility and quality. MAIN RESULTS: Two trials of hands and knees
      posture during pregnancy were included. In one trial involving 100 women, four
      different postures (four groups of 20 women) were combined for the comparison
      with the control group of 20 women. Lateral or posterior position of the
      presenting part of the fetus was less likely to persist following 10 minutes in
      the hands and knees position compared to a sitting position (one trial, 100
      women, relative risk (RR) 0.25, 95% confidence interval (CI) 0.17 to 0.37). In a
      second trial including 2547 women, advice to assume the hands and knees posture
      for 10 minutes twice daily in the last weeks of pregnancy had no effect on the
      baby's position at delivery or any of the other pregnancy outcomes measured. No
      trials of hands and knees posture during labour were included. AUTHORS'
      CONCLUSIONS: Use of hands and knees position for 10 minutes twice daily to
      correct occipitoposterior position of the fetus in late pregnancy cannot be
      recommended as an intervention. This is not to suggest that women should not
      adopt this position if they find it comfortable. The use of this position during
      labour has not been addressed in this review. In view of the promising short-term
      effects of the technique and its simplicity, further trials are justified to
      determine whether encouraging the use of hands and knees posture during rather
      than before labour, has any effect on substantive outcomes.

PMID- 15846612
TI  - Corticosteroids for pulmonary sarcoidosis.
AB  - BACKGROUND: Pulmonary sarcoidosis is a common condition with an unpredictable
      course. Oral (OCS) or inhaled steroids (ICS) are widely used in its treatment,
      but there is no consensus about when and in whom therapy should be initiated,
      what dose should be given and for how long. Corticosteroids given for several
      months have deleterious side-effects so it is important to know whether they have
      any maintained benefit in pulmonary sarcoidosis. OBJECTIVES: To determine the
      randomised controlled trial (RCT) evidence for the benefit of corticosteroids
      (oral or inhaled) in the treatment of pulmonary sarcoidosis. SEARCH STRATEGY:
      MEDLINE, EMBASE and CENTRAL were searched using predefined terms. Bibliographies
      of retrieved RCTs and reviews were searched for additional RCTs. Pharmaceutical
      companies and authors of identified RCTs were contacted for other published and
      unpublished studies. Searches are current as of May 2004. SELECTION CRITERIA: Two
      reviewers independently assessed full text articles for inclusion based upon the
      following criteria: the study had to be a RCT or controlled clinical trial in
      adults with histological evidence of pulmonary sarcoidosis, treated with OCS
      (oral steroids) or ICS (oral steroids), compared with a control. DATA COLLECTION
      AND ANALYSIS: Study quality was assessed and data extracted independently by two
      reviewers. The primary outcome was CXR (chest x-ray). Outcomes were analysed as
      continuous and dichotomous outcomes, using standard statistical techniques.
      Heterogeneity was explored where it was identified. MAIN RESULTS: Twelve RCTs of
      variable quality involving 1051 participants met the inclusion criteria of the
      review. The oral steroid dose was equivalent to prednisolone 4-40 mg/day. OCS:
      there was an improvement in CXR over 3-24 months (Relative Risk (RR): 1.46 [1.01
      to 2.09], 3 studies), but this finding requires cautious interpretation. No other
      significant differences were identified on secondary outcomes. ICS: Data were
      inadequate to perform meaningful analysis of data on CXR. Two studies showed no
      improvement in lung function, In one study there was an improvement in diffusing
      capacity in the treated group. There were no data on side-effects. In one study
      symptoms improved at the end of six months of treatment. AUTHORS' CONCLUSIONS:
      Oral steroids improved the chest X-ray and a global score of CXR, symptoms and
      spirometry over 3-24 months. However, there is little evidence of an improvement
      in lung function. There are limited data beyond two years to indicate whether
      oral steroids have any modifying effect on long-term disease progression. Oral
      steroids may be of benefit for patients with Stage 2 and 3 disease with moderate
      to severe or progressive symptoms or CXR changes.

PMID- 15846613
TI  - Reminiscence therapy for dementia.
AB  - BACKGROUND: Reminiscence Therapy (RT) involves the discussion of past activities,
      events and experiences with another person or group of people, usually with the
      aid of tangible prompts such as photographs, household and other familiar items
      from the past, music and archive sound recordings. Reminiscence groups typically
      involve group meetings in which participants are encouraged to talk about past
      events at least once a week. Life review typically involves individual sessions,
      in which the person is guided chronologically through life experiences,
      encouraged to evaluate them, and may produce a life story book. Family care
      givers are increasingly involved in reminiscence therapy. Reminiscence therapy is
      one of the most popular psychosocial interventions in dementia care, and is
      highly rated by staff and participants. There is some evidence to suggest it is
      effective in improving mood in older people without dementia. Its effects on
      mood, cognition and well-being in dementia are less well understood. OBJECTIVES:
      The objective of the review is to assess the effects of reminiscence therapy for
      older people with dementia and their care-givers. SEARCH STRATEGY: The trials
      were identified from a search of the Specialised Register of the Cochrane
      Dementia and Cognitive Improvement Group on 4 May 2004 using the term
      "reminiscence". The CDCIG Specialized Register contains records from all major
      health care databases (MEDLINE, EMBASE, PsycLIT, CINAHL) and many ongoing trials
      databases and is regularly updated. We contacted specialists in the field and
      also searched relevant Internet sites. We hand-searched Aging and Mental Health,
      the Gerontologist, Journal of Gerontology, Current Opinion in Psychiatry, Current
      Research in Britain: Social Sciences, British Psychological Society conference
      proceedings and Reminiscence database. SELECTION CRITERIA: Randomised controlled
      trials and quasi-randomized trials of reminiscence therapy for dementia. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed
      trial quality. MAIN RESULTS: Five trials are included in the review, but only
      four trials with a total of 144 participants had extractable data. The results
      were statistically significant for cognition (at follow-up), mood (at follow-up)
      and on a measure of general behavioural function (at the end of the intervention
      period). The improvement on cognition was evident in comparison with both no
      treatment and social contact control conditions. Care-giver strain showed a
      significant decrease for care-givers participating in groups with their relative
      with dementia, and staff knowledge of group members' backgrounds improved
      significantly. No harmful effects were identified on the outcome measures
      reported. AUTHORS' CONCLUSIONS: Whilst four suitable randomized controlled trials
      looking at reminiscence therapy for dementia were found, several were very small
      studies, or were of relatively low quality, and each examined different types of
      reminiscence work. Although there are a number of promising indications, in view
      of the limited number and quality of studies, the variation in types of
      reminiscence work reported and the variation in results between studies, the
      review highlights the urgent need for more and better designed trials so that
      more robust conclusions may be drawn.

PMID- 15846614
TI  - Substitution of doctors by nurses in primary care.
AB  - BACKGROUND: Demand for primary care services has increased in developed countries
      due to population ageing, rising patient expectations, and reforms that shift
      care from hospitals to the community. At the same time, the supply of physicians
      is constrained and there is increasing pressure to contain costs. Shifting care
      from physicians to nurses is one possible response to these challenges. The
      expectation is that nurse-doctor substitution will reduce cost and physician
      workload while maintaining quality of care. OBJECTIVES: Our aim was to evaluate
      the impact of doctor-nurse substitution in primary care on patient outcomes,
      process of care, and resource utilisation including cost. Patient outcomes
      included: morbidity; mortality; satisfaction; compliance; and preference. Process
      of care outcomes included: practitioner adherence to clinical guidelines;
      standards or quality of care; and practitioner health care activity (e.g.
      provision of advice). Resource utilisation was assessed by: frequency and length
      of consultations; return visits; prescriptions; tests and investigations;
      referral to other services; and direct or indirect costs. SEARCH STRATEGY: The
      following databases were searched for the period 1966 to 2002: Medline; Cinahl;
      Bids, Embase; Social Science Citation Index; British Nursing Index; HMIC; EPOC
      Register; and Cochrane Controlled Trial Register. Search terms specified the
      setting (primary care), professional (nurse), study design (randomised controlled
      trial, controlled before-and-after-study, interrupted time series), and subject
      (e.g. skill mix). SELECTION CRITERIA: Studies were included if nurses were
      compared to doctors providing a similar primary health care service (excluding
      accident and emergency services). Primary care doctors included: general
      practitioners, family physicians, paediatricians, general internists or
      geriatricians. Primary care nurses included: practice nurses, nurse
      practitioners, clinical nurse specialists, or advanced practice nurses. DATA
      COLLECTION AND ANALYSIS: Study selection and data extraction was conducted
      independently by two reviewers with differences resolved through discussion. Meta
      analysis was applied to outcomes for which there was adequate reporting of
      intervention effects from at least three randomised controlled trials. Semi
      quantitative methods were used to synthesize other outcomes. MAIN RESULTS: 4253
      articles were screened of which 25 articles, relating to 16 studies, met our
      inclusion criteria. In seven studies the nurse assumed responsibility for first
      contact and ongoing care for all presenting patients. The outcomes investigated
      varied across studies so limiting the opportunity for data synthesis. In general,
      no appreciable differences were found between doctors and nurses in health
      outcomes for patients, process of care, resource utilisation or cost. In five
      studies the nurse assumed responsibility for first contact care for patients
      wanting urgent consultations during office hours or out-of-hours. Patient health
      outcomes were similar for nurses and doctors but patient satisfaction was higher
      with nurse-led care. Nurses tended to provide longer consultations, give more
      information to patients and recall patients more frequently than did doctors. The
      impact on physician workload and direct cost of care was variable. In four
      studies the nurse took responsibility for the ongoing management of patients with
      particular chronic conditions. The outcomes investigated varied across studies so
      limiting the opportunity for data synthesis. In general, no appreciable
      differences were found between doctors and nurses in health outcomes for
      patients, process of care, resource utilisation or cost. AUTHORS' CONCLUSIONS:
      The findings suggest that appropriately trained nurses can produce as high
      quality care as primary care doctors and achieve as good health outcomes for
      patients. However, this conclusion should be viewed with caution given that only
      one study was powered to assess equivalence of care, many studies had
      methodological limitations, and patient follow-up was generally 12 months or
      less. While doctor-nurse substitution has the potential to reduce doctors'
      workload and direct healthcare costs, achieving such reductions depends on the
      particular context of care. Doctors' workload may remain unchanged either because
      nurses are deployed to meet previously unmet patient need or because nurses
      generate demand for care where previously there was none. Savings in cost depend
      on the magnitude of the salary differential between doctors and nurses, and may
      be offset by the lower productivity of nurses compared to doctors.

PMID- 15846615
TI  - Intravenous aminophylline for acute severe asthma in children over two years
      receiving inhaled bronchodilators.
AB  - BACKGROUND: Since the advent of inhaled beta2-agonists, anticholinergic agents
      and glucocorticoids, the role of aminophylline in paediatric acute asthma has
      become less clear. There remains some consensus that it is beneficial in children
      with acute severe asthma, receiving maximised therapy (oxygen, inhaled
      bronchodilators, and glucocorticoids). OBJECTIVES: To determine if the addition
      of intravenous aminophylline produces a beneficial effect in children with acute
      severe asthma receiving conventional therapy. SEARCH STRATEGY: The Cochrane
      Airways Group register of trials was used to identify relevant studies. The
      latest search was carried out in December 2004 SELECTION CRITERIA: Randomised
      controlled trials comparing intravenous aminophylline with placebo in addition to
      usual care in children met the inclusion criteria. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently assessed studies and extracted data. Disagreement in
      the selection of trials was resolved by consensus. Attempts were made to contact
      authors to verify accuracy of data. MAIN RESULTS: Seven trials met the inclusion
      criteria (380 participants). Methodological quality was high. All studies
      recruited children with acute severe asthma and requiring hospital admission. Six
      studies sought participants who were unresponsive to nebulised short-acting beta
      agonist and administered systemic steroids to study participants. In two studies
      where some children were able to perform spirometry, baseline FEV1 was between 35
      and 45% predicted. The addition of aminophylline to steroids and beta2-agonist
      significantly improved FEV1% predicted over placebo at 6-8 hours, 12-18 hours and
      24 hours. Aminophylline led to a greater improvement in PEF% predicted over
      placebo at 12-18 hours. There was no significant difference in length of hospital
      stay, symptoms, frequency of nebulsations and mechanical ventilation rates. There
      were insufficient data to permit aggregation for oxygenation and duration of
      supplemental oxygen therapy. Aminophylline led to a three-fold increase in the
      risk of vomiting. There was no significant difference between treatment groups
      with regard to hypokalaemia, headaches, tremour, seizures, arrhythmias and
      deaths. AUTHORS' CONCLUSIONS: In children with a severe asthma exacerbation, the
      addition of intravenous aminophylline to beta2-agonists and glucocorticoids (with
      or without anticholinergics) improves lung function within 6 hours of treatment.
      However there is no apparent reduction in symptoms, number of nebulised treatment
      and length of hospital stay. There is insufficient evidence to assess the impact
      on oxygenation, PICU admission and mechanical ventilation. Aminophylline is
      associated with a significant increased risk of vomiting.

PMID- 15846616
TI  - Individual behavioural counselling for smoking cessation.
AB  - BACKGROUND: Individual counselling from a smoking cessation specialist may help
      smokers to make a successful attempt to stop smoking. OBJECTIVES: The objective
      of the review is to determine the effects of individual counselling. SEARCH
      STRATEGY: We searched the Cochrane Tobacco Addiction Group Specialized Register
      for studies with counsel* in any field. Date of the most recent search: December
      2004. SELECTION CRITERIA: Randomized or quasi-randomized trials with at least one
      treatment arm consisting of face-to-face individual counselling from a healthcare
      worker not involved in routine clinical care. The outcome was smoking cessation
      at follow up at least six months after the start of counselling. DATA COLLECTION
      AND ANALYSIS: Both authors extracted data. The intervention and population,
      method of randomization and completeness of follow up were recorded. MAIN
      RESULTS: We identified 21 trials with over 7000 participants. Eighteen trials
      compared individual counselling to a minimal behavioural intervention, four
      compared different types or intensities of counselling. Individual counselling
      was more effective than control. The odds ratio for successful smoking cessation
      was 1.56 (95% confidence interval 1.32 to 1.84). In a subgroup of three trials
      where all participants received nicotine replacement therapy the point estimate
      of effect was smaller and did not reach significance (odds ratio 1.34, 95%
      confidence interval 0.98 to 1.83). We failed to detect a greater effect of
      intensive counselling compared to brief counselling (odds ratio 0.98, 95%
      confidence interval 0.61 to 1.56). AUTHORS' CONCLUSIONS: Smoking cessation
      counselling can assist smokers to quit.

PMID- 15846617
TI  - Surgery for degenerative lumbar spondylosis.
AB  - BACKGROUND: Surgical investigations and interventions account for large health
      care utilisation and costs, but the scientific evidence for most procedures is
      still limited. OBJECTIVES: Degenerative conditions affecting the lumbar spine are
      variously described as lumbar spondylosis or degenerative disc disease (which we
      regarded as one entity) and may be associated with back pain and associated leg
      symptoms, instability, spinal stenosis and/or degenerative spondylolisthesis. The
      objective of this review was to assess current scientific evidence on the
      effectiveness of surgical interventions for degenerative lumbar spondylosis.
      SEARCH STRATEGY: We searched CENTRAL, MEDLINE, PubMed, Spine and ISSLS abstracts,
      with citation tracking from the retrieved articles. We also corresponded with
      experts. All data found up to 31 March 2004 are included. SELECTION CRITERIA:
      Randomised (RCTs) or quasi-randomised trials of surgical treatment of lumbar
      spondylosis. DATA COLLECTION AND ANALYSIS: Two authors assessed trial quality and
      extracted data from published papers. Additional information was sought from the
      authors if necessary. MAIN RESULTS: Thirty-one published RCTs of all forms of
      surgical treatment for degenerative lumbar spondylosis were identified. The
      trials varied in quality: only the more recent trials used appropriate methods of
      randomization, blinding and independent assessment of outcome. Most of the
      earlier published results were of technical surgical outcomes with some crude
      ratings of clinical outcome. More of the recent trials also reported patient
      centered outcomes of pain or disability, but there is still very little
      information on occupational outcomes. There was a particular lack of long term
      outcomes beyond two to three years. Seven heterogeneous trials on
      spondylolisthesis, spinal stenosis and nerve compression permitted limited
      conclusions. Two new trials on the effectiveness of fusion showed conflicting
      results. One showed that fusion gave better clinical outcomes than conventional
      physiotherapy, while the other showed that fusion was no better than a modern
      exercise and rehabilitation programme. Eight trials showed that instrumented
      fusion produced a higher fusion rate (though that needs to be qualified by the
      difficulty of assessing fusion in the presence of metal-work), but did not
      improve clinical outcomes, while there is other evidence that it may be
      associated with higher complication rates. Three trials with conflicting results
      did not permit any conclusions about the relative effectiveness of anterior,
      posterior or circumferential fusion. Preliminary results of two small trials of
      intra-discal electrotherapy showed conflicting results. Preliminary data from
      three trials of disc arthroplasty did not permit any firm conclusions. AUTHORS'
      CONCLUSIONS: Limited evidence is now available to support some aspects of
      surgical practice. Surgeons should be encouraged to perform further RCTs in this
      field.

PMID- 15846618
TI  - Surgical versus conservative interventions for anterior cruciate ligament
      ruptures in adults.
AB  - BACKGROUND: Anterior cruciate ligament rupture is a common knee injury. Surgical
      treatment, usually involving reconstruction of the ligament, is widely used
      especially in active individuals. OBJECTIVES: Evaluation of the effect of
      surgical treatment compared with conservative treatment of anterior cruciate
      ligament (ACL) rupture. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal
      Injuries Group Specialised Register (January 2005), the Cochrane Central Register
      of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to
      January Week 3 2005), EMBASE (1988 to 2005 Week 05), MEDIC (1978 to January
      1999), Current Contents (9.2.1998 to 1.2.1999), BIOSIS (1970 to December 1998),
      reference lists of articles and consulted trialists and experts. SELECTION
      CRITERIA: All randomised and quasi-randomised trials that compared surgical with
      conservative treatment of ACL rupture in adults. DATA COLLECTION AND ANALYSIS:
      Two authors independently performed study selection, data extraction and quality
      assessment. MAIN RESULTS: Two poor quality randomised trials conducted in the
      early 1980s were included in the review. The two trials differed considerably and
      no data pooling was done for the few shared outcome measures. One quasi
      randomised trial of 167 people with a complete ACL rupture treated with repair or
      augmented repair versus conservative treatment found no difference in the return
      to sports activities between people treated surgically and those treated
      conservatively. Measures of knee stability and functional (Lysholm) knee scores
      were higher in surgically-treated participants. By the end of the follow-up
      period (average 55 months), three people treated with repair only and 16 treated
      conservatively had had ACL reconstruction. The other trial included 157 people
      with ACL injury. This found that conservatively-treated participants recovered
      from their injury more rapidly but, at the last follow up (minimum 13 months),
      the functional outcome was similar in both treatment groups. A large proportion
      of participants experienced some temporary discomfort after surgery and there
      were some more serious postoperative complications. There was less knee
      instability in surgically-treated participants and a tendency to fewer subsequent
      operations in the longer term. AUTHORS' CONCLUSIONS: There is insufficient
      evidence from randomised trials to determine whether surgery or conservative
      management was best for ACL injury in the 1980s, and no evidence to inform
      current practice. Good quality randomised trials are required to remedy this
      situation.

PMID- 15846619
TI  - Olanzapine for schizophrenia.
AB  - BACKGROUND: Olanzapine is an atypical antipsychotic reported to be effective
      without producing disabling extrapyramidal adverse effects associated with older,
      typical antipsychotic drugs. OBJECTIVES: To determine the clinical effects and
      safety of olanzapine compared with placebo, typical and other atypical
      antipsychotic drugs for schizophrenia and schizophreniform psychoses. SEARCH
      STRATEGY: We updated the first search [Biological Abstracts (1980-1999), The
      Cochrane Library (Issue 2, 1999), EMBASE (1980-1999), MEDLINE (1966-1999),
      PsycLIT (1974-1999) and The Cochrane Schizophrenia Group's Register (October
      2000)] in October 2004 using the Cochrane Schizophrenia's Group's register of
      trials. We also searched references of all included studies for further trials,
      and contacted relevant pharmaceutical companies and authors. SELECTION CRITERIA:
      We included all randomised clinical trials comparing olanzapine with placebo or
      any antipsychotic treatment for people with schizophrenia or schizophreniform
      psychoses. DATA COLLECTION AND ANALYSIS: We independently extracted data and, for
      homogeneous dichotomous data, calculated the random effects relative risk (RR),
      the 95% confidence intervals (CI) and the number needed to treat (NNT) on an
      intention-to-treat basis. For continuous data we calculated weighted mean
      differences. MAIN RESULTS: Fifty five trials are included (total n>10000 people
      with schizophrenia). Attrition from olanzapine versus placebo studies was >50% by
      six weeks, leaving interpretation of results problematic. Olanzapine appeared
      superior to placebo at six weeks for the outcome of 'no important clinical
      response' (any dose, 2 RCTs n=418, RR 0.88 CI 0.8 to 0.1, NNT 8 CI 5 to 27).
      Although dizziness and dry mouth were reported more frequently in the olanzapine
      treated group, this did not reach statistical significance. The olanzapine group
      gained more weight. When compared with typical antipsychotic drugs, data from
      several small trials are incomplete. With high attrition in both groups (14 RCTs,
      n=3344, 38% attrition by six weeks, RR 0.81 CI 0.65 to 1.02) the assumptions
      included in all data are considerable. For the short term outcome of 'no
      important clinical response', olanzapine seems as effective as typical
      antipsychotics (4 RCTs, n=2778, RR 0.90 CI 0.76 to 1.06). People allocated
      olanzapine experienced fewer extrapyramidal adverse effects than those given
      typical antipsychotics. Weight change data for the short term are not
      statistically significant but results between three to 12 months suggest a
      clinically important average gain of four kilograms for people given olanzapine
      (4 RCTs, n=186, WMD 4.62, CI 0.6 to 8.64). Twenty three percent of people in
      trials of olanzapine and other atypical drugs left by eight weeks; 48% by three
      to12 months (11 RCTs, n=1847, RR 0.91 CI 0.82 to 1.00). There is little to choose
      between the atypicals, although olanzapine may cause fewer extrapyramidal adverse
      effects than other drugs in this category. Olanzapine produces more weight gain
      than other atypicals with some differences reaching conventional levels of
      statistical significance (1 RCT, n=980, RR gain at 2 years 1.73 CI 1.49 to 2.00,
      NNH 5 CI 4 to 7). There are very few data for people with first episode illness
      (1 RCT, duration 6 weeks, n=42). For people with treatment-resistant illness
      there were no clear differences between olanzapine and clozapine (4 RCTs, n=457).
      AUTHORS' CONCLUSIONS: The large proportion of participants leaving studies early
      in these trials makes it difficult to draw firm conclusions on olanzapine's
      clinical effects. For people with schizophrenia it may offer antipsychotic
      efficacy with fewer extrapyramidal adverse effects than typical drugs, but more
      weight gain. There is a need for further large, long-term randomised trials with
      more comprehensive data.

PMID- 15846620
TI  - Surgical treatments for ingrowing toenails.
AB  - BACKGROUND: Ingrowing toenails are a common condition which, when recurrent and
      painful, are often treated surgically. OBJECTIVES: To evaluate the effectiveness
      of methods of the surgical treatment of ingrowing toenails. SEARCH STRATEGY:
      Electronic database searching (CENTRAL, MEDLINE, EMBASE, CINAHL) followed by
      investigation of reference lists of the papers identified from the initial
      search. SELECTION CRITERIA: Any randomised (or quasi-randomised) controlled trial
      which compares one form of surgical removal of all or part of a toenail due to
      its impact on the soft tissues to another or others. Studies must have a minimum
      follow period of six months and aim to permanently remove the troublesome portion
      of the nail. DATA COLLECTION AND ANALYSIS: Data extraction was carried out
      independently by the two reviewers using a pre-derived data extraction form and
      entered into RevMan. Categorical outcomes were analysed as odds ratios with 95%
      confidence intervals. MAIN RESULTS: Avulsion with phenol versus surgical
      excision: Phenolisation combined with simple avulsion of a nail is more effective
      than the use of more invasive excisional surgical procedures to prevent
      symptomatic recurrence at six months or more (OR 0.44 CI 95% 0.24 - 0.80).
      Avulsion with phenol versus avulsion without phenol: The addition of phenol, when
      performing a total or partial nail avulsion dramatically reduces the rate of
      symptomatic recurrence, (OR 0.07 95% CI 0.04 - 0.12). This is offset by a
      significant increase in the rate of post-operative infection when phenol is used
      (OR 5.69 95% CI 1.93 - 16.77). AUTHORS' CONCLUSIONS: The evidence suggests that
      simple nail avulsion combined with the use of phenol, compared to surgical
      excisional techniques without the use of phenol, is more effective at preventing
      symptomatic recurrence of ingrowing toenails. The addition of phenol when simple
      nail avulsion is performed dramatically decreases symptomatic recurrence, but at
      the cost of increased post-operative infection.

PMID- 15846621
TI  - Interventions for promoting the initiation of breastfeeding.
AB  - BACKGROUND: Despite the widely documented health benefits of breastfeeding,
      initiation rates remain relatively low in many high-income countries,
      particularly among women in lower income groups. OBJECTIVES: To evaluate the
      effectiveness of interventions which aim to encourage women to breastfeed in
      terms of changes in the number of women who start to breastfeed. SEARCH STRATEGY:
      We searched the Cochrane Pregnancy and Childbirth Group trials register (30 May
      2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library,
      Issue 1, 2003) and the following databases from inception to October 2002:
      MEDLINE, CINAHL, ERIC, Applied Social Sciences, PsychLIT, EMBASE, British Nursing
      Index, BIDS, EPI-centre. We also searched the following in October 2002 for 'grey
      literature: 'SIGLE, DHSS Data, and Dissertation Abstracts. We handsearched the
      Journal of Human Lactation, Health Promotion International and Health Education
      Quarterly from inception to October 1998. We scanned reference lists of all
      articles obtained. SELECTION CRITERIA: Randomised controlled trials, with or
      without blinding, of any breastfeeding promotion intervention in any population
      group except women and infants with a specific health problem. DATA COLLECTION
      AND ANALYSIS: One review author independently extracted data and assessed trial
      quality for checking by a second author. We contacted investigators to obtain
      missing information. MAIN RESULTS: Seven trials involving 1388 women were
      included. Five trials involving 582 women on low incomes in the USA showed
      breastfeeding education had a significant effect on increasing initiation rates
      compared to routine care (relative risk (RR) 1.53, 95% confidence interval (CI)
      1.25 to 1.88). AUTHORS' CONCLUSIONS: Evidence from this review shows that the
      forms of breastfeeding education evaluated were effective at increasing
      breastfeeding initiation rates among women on low incomes in the USA.

PMID- 15846622
TI  - Surgical approaches and ancillary techniques for internal fixation of
      intracapsular proximal femoral fractures.
AB  - BACKGROUND: In the fixation of intracapsular hip fractures, different implants,
      surgical approaches and ancillary manoeuvres have been employed to improve the
      reduction, and the stability of the reconstruction, in an attempt to reduce the
      frequency of non-union and aseptic necrosis of the femoral head. OBJECTIVES: To
      compare alternative surgical approaches and ancillary techniques in internal
      fixation of intracapsular hip fractures which have been subjected to randomised
      and quasi-randomised trials in adults. SEARCH STRATEGY: The Cochrane
      Musculoskeletal Injuries Group Specialised Register, MEDLINE, and reference lists
      of relevant articles were searched. Date of the most recent search: November
      2004. SELECTION CRITERIA: All randomised and quasi-randomised trials
      investigating operative technique for the treatment of intracapsular hip
      fractures. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial
      quality, by use of a 10 item checklist, and extracted data. MAIN RESULTS: One
      trial with 103 participants studied the effect of impaction of the fracture at
      the time of surgery. The only outcome measure reported was bone scintimetry.
      There was some evidence that impaction, particularly of displaced fractures,
      resulted in a reduction of blood flow to the femoral head as assessed by bone
      scintimetry. One quasi-randomised trial with 220 participants compared
      compression of the fracture with no compression. Results for 156 individuals at
      one year showed a tendency to a lower incidence of non-union for those fractures
      treated without compression.Two trials, one involving 102 young adults under 50
      years old and the other involving 49 older people aged 65 years or over, compared
      open versus closed reduction of the fracture. Both found open reduction
      significantly increased length of surgery. None of the other differences between
      open and closed reduction in the outcomes reported by the two trials were
      statistically significant. AUTHORS' CONCLUSIONS: Insufficient evidence exists
      from randomised trials to confirm the relative effects of open versus closed
      reduction of intracapsular fractures, or the effects of intra-operative impaction
      or compression of an intracapsular fracture treated by internal fixation.

PMID- 15846623
TI  - Aerobic exercise interventions for adults living with HIV/AIDS.
AB  - BACKGROUND: The profile of HIV infection is constantly changing. Although once
      viewed as an illness progressing to death, among those with access to
      antiretroviral therapy, HIV can now present as a disease with an uncertain
      natural history, perhaps a chronic manageable disease for some. This increased
      chronicity of HIV infection has been mirrored by increased prevalence of
      disablement in the HIV-infected population (Rusch 2004). Thus, the needs of these
      individuals have increasingly included the management of impairments (problems
      with body function or structure as a significant deviation or loss, such as pain
      or weakness), activity limitations (difficulties an individual may have in
      executing activities, such as inability to walk) and participation restrictions
      (problems an individual may experiences in involvement in life situations, such
      as inability to work) (WHO 2001). Exercise is a key strategy employed by people
      living with HIV/AIDS and by rehabilitation professionals to address these issues.
      Exercise has been shown to improve strength, cardiovascular function and
      psychological status in seronegative populations (Bouchard 1993), but what are
      the effects of exercise for adults living with HIV? If the risks and benefits of
      exercise for people living with HIV are better understood, appropriate exercise
      may be undertaken by those living with HIV/AIDS and appropriate exercise
      prescription may be practiced by healthcare providers. If effective and safe,
      exercise may enhance the effectiveness of HIV management, thus improving the
      overall outcome for adults living with HIV. OBJECTIVES: To examine the safety and
      effectiveness of aerobic exercise interventions on immunological/virological,
      cardiopulmonary and psychological parameters in adults living with HIV/AIDS.
      SEARCH STRATEGY: To identify the appropriate studies, we conducted a search using
      MEDLINE, EMBASE, SCIENCE CITATION INDEX, AIDSLINE, CINAHL, HEALTHSTAR, PSYCHLIT,
      SOCIOFILE, SCI, SSCI, ERIC and DAI. We also reviewed both published and
      unpublished abstracts and proceedings from major international and national
      HIV/AIDS conferences such as the Intersciences Conference on Antimicrobial Agents
      and Chemotherapy (ICAAC), the Conference on Retroviruses and Opportunistic
      Infections (CROI), the Infectious Diseases Society of America Conference (IDSA)
      and the International AIDS Conference (IAC). Reference lists from pertinent
      articles and books were reviewed and personal contacts with authors were used, as
      well as Collaborative Review Group databases. Targeted journals were handsearched
      for relevant articles. There were no language restrictions. Searches for the
      original review covered the period from 1980 to July 1999. The first update of
      this review included an additional search of the literature, followed by
      identification of included studies that met the inclusion criteria from August
      1999 to January 2001. For the second update, we conducted a search to identify
      additional studies published from February 2001 to August 2003. SELECTION
      CRITERIA: Studies were included if they were randomized controlled trials (RCTs)
      comparing aerobic exercise interventions with no aerobic exercise interventions
      or another exercise or treatment modality, performed at least three times per
      week for at least four weeks among adults (18 years of age or older) living with
      HIV/AIDS. DATA COLLECTION AND ANALYSIS: Data on study design, participants,
      interventions, outcomes and methodological quality were abstracted from studies
      that met the inclusion criteria onto specifically designed data collection forms
      by at least two reviewers. Meta-analysis was conducted using RevMan 4.2 computer
      software on outcomes whenever possible. MAIN RESULTS: A total of 10 studies (six
      from the original search, two from the first updated search and two from this
      second updated search) met the inclusion criteria for this review. Main results
      indicated that performing constant or interval aerobic exercise, or a combination
      of constant aerobic exercise and progressive resistive exercise for at least 20
      minutes, at least three times per week for four weeks appears to be safe and may
      lead to significant reductions in depressive symptoms and potentially clinically
      important improvements in cardiopulmonary fitness. These findings are limited to
      those participants who continued to exercise and for whom there was adequate
      follow-up data. AUTHORS' CONCLUSIONS: Aerobic exercise appears to be safe and may
      be beneficial for adults living with HIV/AIDS. These findings are limited by the
      small sample sizes and large withdrawal rates of the included studies. Future
      research would benefit from an increased attention to participant follow-up and
      intention-to-treat analysis. Further research is required to determine the
      optimal parameters of aerobic exercise and stage of disease in which aerobic
      exercise may be most beneficial for adults living with HIV.

PMID- 15846624
TI  - Antibiotics for trachoma.
AB  - BACKGROUND: Trachoma is the world's leading cause of preventable blindness. In
      1997 the World Health Organization launched an initiative on trachoma control
      based on the 'SAFE' strategy (surgery, antibiotics, facial cleanliness and
      environmental improvement). OBJECTIVES: To assess the evidence supporting the
      antibiotic arm of the SAFE strategy by assessing the effects of antibiotics on
      both active trachoma (primary objective) and on Chlamydia trachomatis infection
      of the conjunctiva (secondary objective). SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials - CENTRAL (which contains the
      Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library Issue 1,
      2005), MEDLINE (1966 to February 2005), and EMBASE (1980 to February 2005). We
      used the Science Citation Index to look for articles that cited the included
      studies. We searched the reference lists of identified articles and we contacted
      authors and experts for details of further relevant studies. SELECTION CRITERIA:
      We included only randomised trials that satisfied either of two criteria: (a)
      trials in which topical or oral administration of an antibiotic was compared to
      placebo or no treatment in people with trachoma, (b) trials in which a topical
      antibiotic was compared with an oral antibiotic in people with trachoma. A
      subdivision of particular interest was of trials in which topical
      tetracycline/chlortetracycline was compared with oral azithromycin, as these are
      the two World Health Organization recommended treatments. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed trial quality and extracted data. We
      contacted investigators for missing data. MAIN RESULTS: We found 15 studies that
      randomised a total of 8678 participants. For both outcomes (active trachoma and
      laboratory evidence of infection) the results of the chi squared tests suggested
      that there was significant statistical heterogeneity among the trials. There was
      also marked clinical heterogeneity. No summary statistics were calculated and we
      therefore present a narrative summary of the results. For the comparisons of oral
      or topical antibiotic against placebo/no treatment, the data are consistent with
      there being no effect of antibiotics but are suggestive of a lowering of the
      point prevalence of relative risk of both active disease and laboratory evidence
      of infection at three and 12 months after treatment. For the comparison of oral
      against topical antibiotics the results suggest that oral treatment is neither
      more nor less effective than topical treatment. AUTHORS' CONCLUSIONS: There is
      some evidence that antibiotics reduce active trachoma but results are not
      consistent and cannot be pooled.

PMID- 15846625
TI  - Nutritional supplementation for hip fracture aftercare in older people.
AB  - BACKGROUND: Fractures of the hip are an important cause of later ill health and
      mortality in older people. People with hip fractures are often malnourished at
      the time of fracture, and have poor food intake in hospital. OBJECTIVES: This
      review assesses the effects of nutritional interventions in older people
      recovering from hip fracture. SEARCH STRATEGY: We searched the Cochrane
      Musculoskeletal Injuries Group Specialised Register, the Cochrane Central
      Register of Controlled Trials (The Cochrane Library issue 3, 2004), MEDLINE (1966
      to October week 1 2004), Nutrition Abstracts and Reviews, EMBASE, BIOSIS, CINAHL,
      HEALTHSTAR, the National Research Register and reference lists. We contacted
      investigators and handsearched four nutrition journals. SELECTION CRITERIA:
      Randomised and quasi-randomised trials of nutritional interventions for mainly
      older people (aged over 65 years) with hip fracture. DATA COLLECTION AND
      ANALYSIS: Both authors independently selected trials, extracted data and assessed
      trial quality. We sought additional information from all trialists, and pooled
      data for primary outcomes. MAIN RESULTS: Eighteen randomised trials involving
      1306 participants were included. Overall trial quality was poor; specifically in
      terms of allocation concealment, assessor blinding and intention-to-treat
      analysis. This, and the limited availability of outcome data, mean that the
      following results must be interpreted with caution. Eight trials evaluated oral
      multinutrient feeds: these provided non-protein energy, protein, some vitamins
      and minerals. Oral feeds had no statistically significant effect on mortality
      (15/161 versus 17/176; relative risk (RR) 0.89, 95% confidence interval (CI) 0.47
      to 1.68) but may reduce 'unfavourable outcome' (combined outcome of mortality and
      survivors with complications) (14/66 versus 26/73; RR 0.52, 95% CI 0.32 to 0.84).
      Four trials examining nasogastric multinutrient feeding showed no evidence of an
      effect on mortality (RR 0.99, 95% CI 0.50 to 1.97), but the studies were
      heterogeneous regarding case mix. There was insufficient information for other
      outcomes. The specific effect of protein given in an oral feed was tested in
      three trials. There was no evidence for an effect on mortality (RR 1.38, 95% CI
      0.82 to 2.34). Protein supplementation may have reduced the number of long term
      complications and days spent in rehabilitation wards. Two trials, testing
      intravenous thiamin (vitamin B1) and other water soluble vitamins, or 1-alpha
      hydroxycholecalciferol (an active form of vitamin D) respectively, produced no
      evidence of effect for either vitamin supplement. AUTHORS' CONCLUSIONS: While
      some evidence exists for the effectiveness of oral protein and energy feeds,
      overall the evidence for the effectiveness of nutritional supplementation remains
      weak. Future trials are required which overcome the defects of the reviewed
      studies, particularly inadequate size, methodology and outcome assessment.

PMID- 15846626
TI  - Cyclo-oxygenase (COX) inhibitors for treating preterm labour.
AB  - BACKGROUND: Preterm birth is a major cause of perinatal mortality and morbidity.
      Cyclo-oxygenase (COX) inhibitors inhibit uterine contractions, are easily
      administered and have fewer maternal side-effects compared to conventional
      tocolytics. However, adverse effects have been reported on the fetus and newborn
      as a result of exposure to COX inhibitors. OBJECTIVES: To assess the effects on
      maternal, fetal and neonatal outcomes of COX inhibitors administered as a
      tocolytic agent to women in preterm labour when compared with (i) placebo or no
      intervention and (ii) other tocolytics. In addition, to compare the effects of
      non-selective COX inhibitors with COX-2 selective inhibitors. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group's trials register (August
      2004). We also contacted recognised experts and cross referenced relevant
      material. SELECTION CRITERIA: All published and unpublished randomised trials in
      which COX inhibitors were used for tocolysis for women in labour between 20 and
      36 completed weeks' gestation. DATA COLLECTION AND ANALYSIS: Three authors
      independently evaluated methodological quality and extracted data. We sought
      additional information from trial authors. MAIN RESULTS: This review includes
      outcome data from 13 trials with a total of 713 women. The non-selective COX
      inhibitor, indomethacin was used in 10 trials. When compared with placebo, COX
      inhibition (indomethacin only) resulted in a reduction in birth before 37 weeks'
      gestation (relative risk (RR) 0.21; one trial, 36 women), an increase in
      gestational age (weighted mean difference (WMD) 3.53 weeks) and birthweight (WMD
      716.34 gm; two trials, 67 women). Compared to any other tocolytic, COX inhibition
      resulted in a reduction in birth before 37 weeks' gestation (RR 0.53; three
      trials, 168 women) and a reduction in maternal drug reaction requiring cessation
      of treatment (RR 0.07; five trials and 355 women). A comparison of non-selective
      COX inhibitors versus any COX-2 inhibitor (two trials, 54 women) did not
      demonstrate any differences in maternal or neonatal outcomes. Due to small
      numbers, all estimates of effect are imprecise and need to be interpreted with
      caution. Potential adverse effects of COX inhibition on the fetus, newborn or
      mother could not be adequately assessed due to insufficient data. AUTHORS'
      CONCLUSIONS: There is insufficient information on which to base decisions about
      the role of COX inhibition for women in preterm labour. Further well designed
      trials are needed.

PMID- 15846627
TI  - Single versus combination intravenous antibiotic therapy for people with cystic
      fibrosis.
AB  - BACKGROUND: Choice of antibiotic, and the use of single or combined therapy are
      controversial areas in the treatment of respiratory infection in cystic fibrosis
      (CF). Advantages of combination therapy include wider range of modes of action,
      possible synergy and reduction of resistant organisms; advantages of monotherapy
      include lower cost, ease of administration and reduction of drug-related
      toxicity. Current evidence does not provide a clear answer and the use of
      intravenous antibiotic therapy in CF requires further evaluation. OBJECTIVES: To
      assess the effectiveness of single compared to combination intravenous antibiotic
      therapy for treating people with CF. SEARCH STRATEGY: We searched the Cochrane
      Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising
      references identified from comprehensive electronic database searches and
      handsearches of relevant journals and abstract books of conference proceedings.
      Most recent search of the Group's register: January 2004. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) comparing a single intravenous antibiotic
      with a combination of that antibiotic plus a second antibiotic in people with CF.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality
      and extracted data. MAIN RESULTS: Twenty-seven trials were identified, of which
      eight trials (with 356 participants) comparing a single agent to a combination of
      the same antibiotic and one other, were included. There was a wide variation in
      the individual antibiotics used in each trial. In total, the trials included
      seven comparisons of a beta-lactam antibiotic (penicillin-related or third
      generation cephalosporin) with a beta-lactam-aminoglycoside combination and three
      comparisons of an aminoglycoside with a beta-lactam-aminoglycoside combination.
      These two groups of trials were analysed as separate subgroups. There was
      considerable heterogeneity amongst these trials, leading to difficulties in
      performing the review and interpreting the results. The meta-analysis did not
      demonstrate any significant differences between monotherapy and combination
      therapy, in terms of lung function; symptom scores; adverse effects; and
      bacteriological outcome measures. These results should be interpreted cautiously.
      Six of the included trials were published between 1977 and 1988; these were
      single centre trials with flaws in the randomisation process and small sample
      size. Overall, the methodological quality was poor. AUTHORS' CONCLUSIONS: The
      results of this review are inconclusive. The review raises important
      methodological issues. There is a need for an RCT which needs to be well designed
      in terms of adequate randomisation allocation, blinding, power and long-term
      follow up. Results need to be standardised to a consistent method of reporting,
      in order to validate the pooling of results from multiple trials.

PMID- 15846628
TI  - Postoperative radiotherapy for non-small cell lung cancer.
AB  - BACKGROUND: The role of postoperative radiotherapy in the treatment of patients
      with completely resected non-small cell lung cancer was not clear. A systematic
      review and quantitative meta-analysis were therefore undertaken to evaluate the
      available evidence from randomised trials. OBJECTIVES: To evaluate the effect of
      post-operative radiotherapy (PORT) on survival and recurrence in patients with
      completely resected non-small cell lung cancer. To investigate whether or not pre
      defined patient subgroups benefit more or less from PORT. SEARCH STRATEGY:
      MEDLINE and CANCERLIT searches were supplemented by information from trial
      registers and by handsearching relevant meeting proceedings and by discussion
      with relevant trialists and organisations. SELECTION CRITERIA: Both published and
      unpublished trials were eligible for inclusion provided the patients had
      undergone a complete resection; had been randomised between radiotherapy and no
      immediate further treatment; that the method of randomisation precluded prior
      knowledge of the treatment to be assigned; and that recruitment was after 1965.
      DATA COLLECTION AND ANALYSIS: A quantitative meta-analysis using updated
      information from individual patients from all available randomised trials was
      carried out. Data from all patients randomised in all eligible trials were sought
      directly from those responsible. Updated information on survival, recurrence and
      date of last follow up were obtained. To avoid potential bias, information was
      requested for all randomised patients including those who had been excluded from
      the investigators' original analyses. MAIN RESULTS: 2232 patients from ten trials
      were included (median follow up of 4.25 years). The results showed a significant
      adverse effect of PORT on survival with a hazard ratio of 1.18 or 18% relative
      increase in the risk of death. This is equivalent to an absolute detriment of 6%
      at two years (95% CI 2% to 9%) reducing overall survival from 58% to 52%.
      Exploratory subgroup analyses suggested that this detrimental effect was most
      pronounced for patients with stage I/II, N0-N1 disease, whereas for stage III, N2
      patients there was no clear evidence of an adverse effect. AUTHORS' CONCLUSIONS:
      PORT is detrimental to patients with early stage completely resected non-small
      cell lung cancer and should not be used in the routine treatment of such
      patients. The role of PORT in the treatment of N2 tumours is not clear and may
      justify further research.

PMID- 15846629
TI  - Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis.
AB  - BACKGROUND: Alcohol and hepatotropic viruses cause the majority of liver
      cirrhosis cases in the Western World. Colchicine is an anti-inflammatory and anti
      fibrotic medication. Several randomised clinical trials have addressed the
      question whether colchicine has any efficacy in patients with alcoholic or non
      alcoholic fibrosis and cirrhosis. OBJECTIVES: To assess the beneficial and
      harmful effects of colchicine in patients with alcoholic or non-alcoholic
      fibrosis or cirrhosis, excluding primary biliary cirrhosis. SEARCH STRATEGY: The
      Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Controlled
      Trials Register on The Cochrane Library, MEDLINE, EMBASE, Web of Science, and
      full text searches were combined (September 2004). Manufacturers and researchers
      in the field were also contacted. SELECTION CRITERIA: We included randomised
      trials irrespective of blinding, language, or publication status comparing per
      oral colchicine with placebo or no intervention for patients with fibrosis or
      cirrhosis induced by either alcohol, virus, or unknown factors (cryptogenic).
      DATA COLLECTION AND ANALYSIS: The statistical package (RevMan Analyses) provided
      by The Cochrane Collaboration was used. The methodological quality of the
      randomised clinical trials was evaluated. MAIN RESULTS: We could include fifteen
      randomised clinical trials in which 1714 patients were randomised. We found no
      significant effects of colchicine on mortality (relative risks (RR) 1.00, 95%
      confidence interval (CI) 0.87 to 1.16), liver-related mortality (RR 1.08, 95% CI
      0.88 to 1.33), complications (RR 1.01, 95% CI 0.74 to 1.38), liver biochemistry,
      liver histology, and alcohol consumption (RR 1.03, 95% CI 0.77 to 1.39).
      Colchicine was associated with a significantly increased risk of adverse events
      (RR 4.35, 95% CI 2.16 to 8.77). AUTHORS' CONCLUSIONS: Colchicine should not be
      used for alcoholic, viral, or cryptogenic liver fibrosis or liver cirrhosis
      outside randomised clinical trials.

PMID- 15846630
TI  - Operative procedures for fissure in ano.
AB  - BACKGROUND: Operative techniques commonly used for fissure in ano include: anal
      stretch, open lateral sphincterotomy, closed lateral sphincterotomy, posterior
      midline sphincterotomy and to a lesser extent dermal flap coverage of the
      fissure. Reports of direct comparisons between operative techniques for anal
      fissure are variable in their results. These reports are either subject to
      selection bias (in non-randomized studies) or observer bias (in all studies) or
      have inadequate numbers of patients enrolled to answer the question of efficacy.
      OBJECTIVES: To determine the best technique for fissure surgery. SEARCH STRATEGY:
      The Cochrane Central Register of Controlled Trials and MEDLINE (1965-2005) were
      searched. The list of cited references in all included reports and several study
      authors also were helpful in finding additional comparative studies. SELECTION
      CRITERIA: All reports in which there was a direct comparison between at least two
      operative techniques were reviewed and when more than one report existed for any
      given pair, that report was included. If crude data were not presented in the
      report, the authors were contacted and crude data obtained. DATA COLLECTION AND
      ANALYSIS: The two most commonly used end points in all reported studies were
      persistence of the fissure and post operative incontinence of flatus. These are
      the only two endpoints included in the meta-analysis. MAIN RESULTS: Twenty-four
      trials encompassing 3475 patients are included in this review . Anal stretch has
      a higher risk of fissure persistence than internal sphincterotomy and also a
      significantly higher risk of minor incontinence than sphincterotomy. The combined
      results of open versus closed partial lateral internal sphincterotomy show little
      difference between the two procedures both in fissure persistence and risk of
      incontinence. AUTHORS' CONCLUSIONS: Anal stretch and posterior midline internal
      sphincterotomy should probably be abandoned in the treatment of chronic anal
      fissure in adults. For those patients requiring surgery for anal fissure, open
      and closed partial lateral internal sphincterotomy appear to be equally
      efficacious. More data are needed to assess the effectiveness of posterior
      internal sphincterotomy, anterior levatorplasty, wound suture or papilla
      excision.

PMID- 15846631
TI  - Hormone replacement therapy for preventing cardiovascular disease in post
      menopausal women.
AB  - BACKGROUND: There is apparently compelling evidence, from observational studies,
      that hormone replacement therapy (HRT) may have benefits in reducing
      cardiovascular events in post-menopausal women. However, these observational data
      are subject to biases and confounding and require support from formally designed
      randomised controlled trials of the effects of HRT on cardiovascular disease
      risk. OBJECTIVES: To assess the effects of HRT for the primary and secondary
      prevention of cardiovascular diseases in post-menopausal women. SEARCH STRATEGY:
      We searched MEDLINE (1998 to December 2002)), EMBASE (1998 to December 2002), the
      Cochrane Controlled Trials Register (CCTR) (Issue 4 2002), the National Research
      Register (1998 to present), Clinical Trials.gov (1998 to present), and the
      database of Spanish Clinical Trials (1998 to present) and reference lists of
      articles. SELECTION CRITERIA: Randomised controlled trials comparing HRT with
      controls (placebo or no treatment) with a minimum follow up of 6 months for
      treating or preventing cardiovascular disease in postmenopausal women with or
      without cardiovascular disease. DATA COLLECTION AND ANALYSIS: Three independent
      reviewers extracted information from the articles, solving discrepancies by
      consensus. All outcomes studied were dichotomous. Risk ratios and 95% confidence
      intervals (CI) were calculated for each study and plotted. Random effects meta
      analysis was used in efficacy outcomes (cardiovascular events) and fixed-effects
      meta-analysis in variables regarding side effects (deep venous thrombosis). MAIN
      RESULTS: No protective effect of HRT was seen for any of the cardiovascular
      outcomes assessed: all cause mortality, cardiovascular death, non-fatal MI,
      venous thromboemboli or stroke. Higher risks of venous thromboembolic events
      (Relative risk (RR) 2.15, 95% CI 1.61 to 2.86), pulmonary embolus (RR 2.15, 95%
      CI 1.41 to 3.28), and stroke (RR 1.44, 95% CI 1.10 to 1.89) was found in those
      randomised to HRT compared with placebo. No substantial heterogeneity (p <0.1)
      was detected in any of the outcomes studied. AUTHORS' CONCLUSIONS: At present, a
      recommendation for initiating HRT for the reason of preventing cardiovascular
      events in post-menopausal women (with or without cardiovascular disease) should
      not be made. Women with other risk factors for venous thromboembolic events
      should be discouraged from using HRT if the sole goal is to prevent
      cardiovascular events.

PMID- 15846632
TI  - Air versus oxygen for resuscitation of infants at birth.
AB  - BACKGROUND: 100% oxygen is the commonly recommended gas for the resuscitation of
      infants at birth. There is growing evidence from both animal and human studies
      that room air is as effective as 100% oxygen and that 100% oxygen may have
      adverse effects on breathing physiology and cerebral circulation. There is also
      the theoretical risk of tissue damage due to free oxygen radicals when 100%
      oxygen is given. The use of room air has, therefore, been suggested as a safer
      and possibly more effective alternative. OBJECTIVES: In newborn infants requiring
      resuscitation, does the use of room air reduce the incidence of death,
      neurological disability and short term morbidity when compared with the use of
      100% oxygen? SEARCH STRATEGY: This included searches of the Oxford Database of
      Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library, Issue 1, 2004) and MEDLINE PubMed 1966 to December 2003, and
      handsearches of reference lists of relevant articles and conference proceedings.
      SELECTION CRITERIA: All randomised and quasi-randomised studies comparing the use
      of room air or any other concentration of oxygen versus 100% oxygen in the
      resuscitation of infants at birth. DATA COLLECTION AND ANALYSIS: Three authors
      assessed the methodological quality of eligible trials and extracted data
      independently. When appropriate, meta-analysis was conducted to provide a pooled
      estimate of effect. For categorical data the relative risk (RR), risk difference
      (RD) and number needed to treat (NNT) with 95% confidence intervals (CI) were
      calculated. Continuous data were analysed using weighted mean difference (WMD).
      MAIN RESULTS: Five studies were identified which enrolled a total of 1302
      infants. In two studies allocation was randomised and the caregivers were blinded
      to intervention group. In the other three studies, allocation was quasi
      randomised and the caregivers were not blinded. Pooled analysis of the four
      trials reporting effect on death showed a significant reduction in the rate of
      death in the group resuscitated with room air [typical RR 0.71 (0.54, 0.94),
      typical RD -0.05 (-0.08, -0.01), NNT 20 (12, 100)]. There were no significant
      differences between the groups with respect to rates of grade 2 or 3 hypoxic
      ischaemic encephalopathy. One of the four trials reported a statistically
      significant difference in median 5 minute Apgar scores, favouring the group
      allocated to room air. However, the absolute difference between the medians was
      small and there were no significant differences in the median 10 minute Apgar
      scores in the three trials reporting this outcome. One trial followed up a
      selected subgroup of survivors to 18-24 months. There were no significant
      differences in rates of adverse neurodevelopmental outcomes including cerebral
      palsy and failure to achieve various milestones; however, the proportion of
      eligible patients seen was less than 70%. Analyses that were planned for this
      review, but not able to be carried out because of lack of published data,
      included a sub-analysis stratified by gestational age and assessments of the
      effect on bronchopulmonary dysplasia and retinopathy of prematurity. AUTHORS'
      CONCLUSIONS: There is insufficient evidence at present on which to recommend a
      policy of using room air over 100% oxygen, or vice versa, for newborn
      resuscitation. A reduction in mortality has been seen in infants resuscitated
      with room air, and no evidence of harm has been demonstrated. However, the small
      number of identified studies and their methodologic limitations dictate caution
      in interpreting and applying these results. We note the use of back-up 100%
      oxygen in more than a quarter of infants randomised to room air. Therefore, on
      the basis of currently available evidence, if one chooses room air as the initial
      gas for resuscitation, supplementary oxygen should continue to be made available.

PMID- 15846633
TI  - Manual versus powered toothbrushing for oral health.
AB  - BACKGROUND: Removing dental plaque may play a key role maintaining oral health.
      There is conflicting evidence for the relative merits of manual and powered
      toothbrushing in achieving this. OBJECTIVES: To compare manual and powered
      toothbrushes in relation to the removal of plaque, the health of the gingivae,
      staining and calculus, dependability, adverse effects and cost. SEARCH STRATEGY:
      We searched the Cochrane Oral Health Group Trials Register (to 17/06/2004) and
      Central Register of Controlled Trials (The Cochrane Library Issue 2, 2004);
      MEDLINE (January 1966 to week 2 June 2004); EMBASE (January 1980 to week 2 2004)
      and CINAHL (January 1982 to week 2 June 2004). Manufacturers were contacted for
      additional data. SELECTION CRITERIA: Trials were selected for the following
      criteria: design-random allocation of participants; participants - general public
      with uncompromised manual dexterity; intervention - unsupervised manual and
      powered toothbrushing for at least 4 weeks. Primary outcomes were the change in
      plaque and gingivitis over that period. DATA COLLECTION AND ANALYSIS: Six authors
      independently extracted information. The effect measure for each meta-analysis
      was the standardised mean difference (SMD) with 95% confidence intervals (CI)
      using random-effects models. Potential sources of heterogeneity were examined,
      along with sensitivity analyses for quality and publication bias. For discussion
      purposes SMD was translated into percentage change. MAIN RESULTS: Forty-two
      trials, involving 3855 participants, provided data. Brushes with a rotation
      oscillation action removed plaque and reduced gingivitis more effectively than
      manual brushes in the short term and reduced gingivitis scores in studies over 3
      months. For plaque at 1 to 3 months the SMD was -0.43 (95% CI: -0.72 to -0.14),
      for gingivitis SMD -0.62 (95% CI: -0.90 to -0.34) representing an 11% difference
      on the Quigley Hein plaque index and a 6% reduction on the Loe and Silness
      gingival index. At over 3 months the SMD for plaque was -1.29 (95% CI: -2.67 to
      0.08) and for gingivitis was -0.51 (-0.76 to -0.25) representing a 17% reduction
      on the Ainamo Bay bleeding on probing index. There was heterogeneity between the
      trials for the short-term follow up. Sensitivity analyses revealed the results to
      be robust when selecting trials of high quality. There was no evidence of any
      publication bias. No other powered designs were as consistently superior to
      manual toothbrushes.Cost, reliability and side effects were inconsistently
      reported. Any reported side effects were localised and temporary. AUTHORS'
      CONCLUSIONS: Powered toothbrushes with a rotation oscillation action reduce
      plaque and gingivitis more than manual toothbrushing. Observation of
      methodological guidelines and greater standardisation of design would benefit
      both future trials and meta-analyses.

PMID- 15846634
TI  - Non-corticosteroid treatment for nephrotic syndrome in children.
AB  - BACKGROUND: Eighty to ninety per cent of children with steroid-sensitive
      nephrotic syndrome (SSNS) have relapses. About half relapse frequently and are at
      risk of the adverse effects of corticosteroids. Non-corticosteroid
      immunosuppressive agents are used to prolong periods of remission in children who
      relapse frequently. However these non-corticosteroid agents also have significant
      potential adverse effects. Currently there is no consensus as to the most
      appropriate second line agent in children who are steroid sensitive, but who
      continue to relapse. OBJECTIVES: To evaluate the benefits and harms of non
      corticosteroid immunosuppressive agents in relapsing SSNS in children. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, reference lists of articles, abstracts from
      proceedings and contact with known investigators. Search date: August 2004
      SELECTION CRITERIA: RCTs or quasi-RCTs were included if they were undertaken in
      children with relapsing SSNS, if they compared non-corticosteroid agents with
      placebo, prednisone or no treatment, different doses and/or durations of the same
      non-corticosteroid agent, different non-corticosteroid agents and outcome data at
      six months. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      trial quality and extracted data. Statistical analyses were performed using a
      random effects model and results expressed as relative risk (RR) with 95%
      confidence intervals (CI). MAIN RESULTS: Twenty trials involving 923 children
      were identified. Cyclophosphamide (three trials: RR 0.44, 95% CI 0.26 to 0.73)
      and chlorambucil (two trials: RR 0.13, 95% CI 0.03 to 0.57) significantly reduced
      the relapse risk at six to twelve months compared with prednisone alone. In the
      single chlorambucil versus cyclophosphamide trial, there was no observed
      difference in relapse risk at two years (RR 1.31, 95% CI 0.80 to 2.13).
      Cyclosporin was as effective as cyclophosphamide (one trial: RR 1.07, 95% CI 0.48
      to 2.35) and chlorambucil (one trial: RR 0.82, 95% CI 0.44 to 1.53) but the
      effect was not sustained when cyclosporin was ceased. During treatment,
      levamisole (three trials: RR 0.60, 95% CI 0.45 to 0.79) was more effective than
      steroids alone but the effect was not sustained. Mizoribine (one trial) and
      azathioprine (two trials) were no more effective than placebo or prednisone alone
      in maintaining remission. AUTHORS' CONCLUSIONS: Eight week courses of
      cyclophosphamide or chlorambucil and prolonged courses of cyclosporin and
      levamisole reduce the risk of relapse in children with relapsing SSNS compared
      with corticosteroids alone. Clinically important differences in efficacy among
      these agents are possible and further comparative trials are still needed.

PMID- 15846635
TI  - Chinese herbal medicine for atopic eczema.
AB  - BACKGROUND: Traditional Chinese herbal mixtures have been used to treat atopic
      eczema for many years. Their efficacy has attracted public attention and recently
      some clinical trials have been undertaken. OBJECTIVES: To assess the effects of
      Chinese herbal mixtures in the treatment of atopic eczema. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( January
      2004), the Cochrane Skin Group Specialised Register (January 2004), MEDLINE (1966
      to January 2004), EMBASE (1980 to January 2004), CINHL (1980 to January 2004) and
      a number of complementary medicine databases. In addition, the cited references
      of all trials identified and key review articles were searched. Pharmaceutical
      companies involved in oral traditional Chinese herbs and experts in the field
      were contacted. SELECTION CRITERIA: Randomised controlled trials of Chinese
      herbal mixtures used in the treatment of atopic eczema. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently applied eligibility criteria, assessed the
      quality of the trials and extracted data. Any discrepancies were discussed to
      achieve consensus. MAIN RESULTS: Four randomised controlled trials, with eight
      weeks for each phase, met the inclusion criteria. The trials randomised 159
      participants aged from 1 to 60 years. The withdrawal rates ranged from 7.5% to
      22.5% and no trial used intention to treat analysis. Three trials were randomised
      placebo controlled, two-phase cross-over designs assessing the same Chinese
      herbal mixture, Zemaphyte. In two of these three trials the reduction in erythema
      and surface damage was greater on Zemaphyte than on placebo, and participants
      slept better and expressed a preference for Zemaphyte. One trial also reported
      that participants itched less. The fourth trial was an open-label design
      comparing Zemaphyte in herbal form with Zemaphyte as a freeze dried preparation.
      There was a reduction in erythema and surface damage with both formulations, but
      no comparison between the two formulations was reported. Some adverse effects
      were reported in all four trials, but none were regarded as serious. AUTHORS'
      CONCLUSIONS: Chinese herbal mixtures may be effective in the treatment of atopic
      eczema. However, only four small poorly reported RCTs of the same product,
      Zemaphyte, were found and the results were heterogeneous. Further well-designed,
      larger scale trials are required, but Zemaphyte is no longer being manufactured.

PMID- 15846636
TI  - Psychological interventions for non-ulcer dyspepsia.
AB  - BACKGROUND: Studies have also shown that non-ulcer dyspepsia (NUD) patients have
      higher scores of anxiety, depression, neurotism, chronic tension, hostility,
      hypochondriasis and tendency to be more pessimistic when compared with the
      community controls. However, the role of psychological interventions in NUD
      remains uncertain. OBJECTIVES: This review aims to determine the effectiveness of
      psychological interventions including psychotherapy, psychodrama, cognitive
      behavioural therapy, relaxation therapy and hypnosis in the improvement of either
      individual or global dyspepsia symptom scores and quality of life scores in
      patients with NUD. SEARCH STRATEGY: Trials were identified by searching the
      Cochrane Controlled Trials Register (Issue 3-1999), MEDLINE (1966-99), EMBASE
      (1988-99), PsycLIT (1987-1999) and CINAHL (1982-99). Bibliographies of retrieved
      articles were also searched and experts in the field were contacted. Searches
      were updated on 10 December 2002 and 21 January 2004. The searches were re-run on
      24 January 2005 and no new trials were found SELECTION CRITERIA: All randomised
      controlled trials (RCTs) or quasi-randomised studies assessing the effectiveness
      of psychological interventions (including psychotherapy, psychodrama, cognitive
      behavioural therapy, relaxation therapy and hypnosis) for non-ulcer dyspepsia
      (NUD) were identified. DATA COLLECTION AND ANALYSIS: Data collected included both
      individual and global dyspepsia symptom scores and quality of life (QoL) scores.
      MAIN RESULTS: We identified only four trials each using different psychological
      interventions; three presented results in a manner that did not allow synthesis
      of the data to form a meta-analysis. All trials suggested that psychological
      interventions benefit dyspepsia symptoms and this effect persists for one year.
      However, all trials used statistical techniques that adjusted for baseline
      differences between groups. This should not be necessary for a randomised trial
      that is adequately powered suggesting that the sample size was too small.
      Unadjusted data was not statistically significant. The other problems of
      psychological intervention included low recruitment and high drop out rate, which
      has been shown to be greater in patients receiving group therapy. AUTHORS'
      CONCLUSIONS: There is insufficient evidence from this review to confirm the
      efficacy of psychological intervention in NUD.

PMID- 15846637
TI  - Inhaled fluticasone versus inhaled beclomethasone or inhaled budesonide for
      chronic asthma in adults and children.
AB  - BACKGROUND: Beclomethasone dipropionate (BDP) and budesonide (BUD) are commonly
      prescribed inhaled corticosteroids for the treatment of asthma. Fluticasone
      propionate (FP) is newer agent with greater potency in in-vitro assays.
      OBJECTIVES: To compare the efficacy and safety of Fluticasone to Beclomethasone
      or Budesonide in the treatment of chronic asthma. SEARCH STRATEGY: We searched
      the Cochrane Airways Group trial register (January 2004) and reference lists of
      articles. We contacted trialists and pharmaceutical companies for additional
      studies and searched abstracts of major respiratory society meetings (1997 to
      2003). SELECTION CRITERIA: Randomised trials in children and adults comparing
      Fluticasone to either Beclomethasone or Budesonide in the treatment of chronic
      asthma. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed
      articles for inclusion and methodological quality. One reviewer extracted data.
      Quantitative analyses were undertaken using RevMan analyses 1.0.1. MAIN RESULTS:
      Fifty six studies (12, 119 participants) met the inclusion criteria.
      Methodological quality was variable. Dose ratio 1:2: FP produced a significantly
      greater FEV1 (0.14 litres, 95% Confidence Interval (CI) 0.06 to 0.22), morning
      PEF (11.10 L/min, 95%CI 3.12 to 19.09 L/min) and evening PEF (9.31 L/min, 95%CI
      5.12 to 13.5 L/min). This applied to all drug doses, age groups, and delivery
      devices. No difference between FP and BDP/BUD were seen for trial withdrawals.
      Symptoms and rescue medication use were widely reported but few trials provided
      sufficient data for analysis. When given at half the dose of BDP/BUD, FP led to a
      greater likelihood of pharyngitis. There was no difference in the likelihood of
      oral candidiasis. Plasma cortisol and 24 hour urinary cortisol was measured
      frequently but data presentation was limited. Dose ratio 1:1: FP produced a
      statistically significant difference in am PEF (9.58 L/min (95% CI 5.20 to
      13.97)), pm PEF (7.41 L/min (95% CI 2.61 to 12.22)), and FEV1 (0.09 L (0.02 to
      0.17)). The effects on exacerbations were mixed. There was an increase in the
      incidence of hoarseness, but no significant difference in pharyngitis,
      candidiasis, or cough. AUTHORS' CONCLUSIONS: Fluticasone given at half the daily
      dose of beclomethasone or budesonide leads to small improvements in measures of
      airway calibre, but it appears to have a higher risk of causing hoarseness when
      given at the same daily dose. Future studies should attempt to establish the
      relative efficacy of inhaled steroids delivered with CFC-free propellants.

PMID- 15846639
TI  - Neuromuscular paralysis for newborn infants receiving mechanical ventilation.
AB  - BACKGROUND: Ventilated newborn infants breathing in asynchrony with the
      ventilator are at risk for complications during mechanical ventilation, such as
      pneumothorax or intraventricular hemorrhage, and are exposed to more severe
      barotrauma, which consequently could impair their clinical outcome. Neuromuscular
      paralysis, which eliminates spontaneous breathing efforts of the infant, has
      potential advantages in this respect. However, a number of complications have
      been reported with muscle relaxation in infants, so that concerns exist regarding
      the safety of prolonged neuromuscular paralysis in newborn infants. OBJECTIVES:
      To determine whether routine neuromuscular paralysis of newborn infants receiving
      mechanical ventilation compared with no routine paralysis results in clinically
      important benefits or harms. SEARCH STRATEGY: The Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004), MEDLINE (from
      1966 to April 2004) and EMBASE (from 1988 to April 2004) were searched.
      References of review articles were hand searched. Language restriction was not
      imposed. SELECTION CRITERIA: All trials using random or quasi-random patient
      allocation, in which the routine use of neuromuscular blocking agents during
      mechanical ventilation was compared to no paralysis or selective paralysis in
      newborn infants. Methodological quality was assessed blindly and independently by
      the two authors. DATA COLLECTION AND ANALYSIS: Data were abstracted using
      standard methods of the Cochrane Collaboration and its Neonatal Review Group,
      with independent evaluation of trial quality, and abstraction and synthesis of
      data by both authors. Treatment effect was analysed using relative risk, risk
      difference and weighted mean difference. MAIN RESULTS: Ten possibly eligible
      trials were identified, of which six were included in the review. All the
      included trials studied preterm infants ventilated for respiratory distress
      syndrome, and used pancuronium as the neuromuscular blocking agent. In the
      analysis of the results of all trials, no significant difference was found in
      mortality, air leak or chronic lung disease, but there was a significant
      reduction in intraventricular hemorrhage and a trend towards less severe
      intraventricular hemorrhages. In the subgroup analysis of trials studying a
      selected population of ventilated infants with evidence of asynchronous
      respiratory efforts, a significant reduction in intraventricular hemorrhage (any
      grade and severe IVH) was found, and a trend towards less air leak. In the
      subgroup analysis of trials studying an unselected population of ventilated
      infants, no significant differences were found for any of the outcomes. AUTHORS'
      CONCLUSIONS: For ventilated preterm infants with evidence of asynchronous
      respiratory efforts, neuromuscular paralysis with pancuronium seems to have a
      favourable effect on intraventricular hemorrhage and possibly on air leak.
      Uncertainty remains, however, regarding the long term pulmonary and neurologic
      effects, and regarding the safety of prolonged use of pancuronium in ventilated
      newborn infants. There is no evidence from randomized trials on the effects of
      neuromuscular blocking agents other than pancuronium. The routine use of
      pancuronium or any other neuromuscular blocking agent in ventilated newborn
      infants cannot be recommended based on current evidence.

PMID- 15846638
TI  - Clinical service organisation for heart failure.
AB  - BACKGROUND: Chronic heart failure (CHF) is a serious, common condition associated
      with frequent hospitalisation. Several different disease management interventions
      (clinical service organisation interventions) for patients with CHF have been
      proposed. OBJECTIVES: To assess the effectiveness of disease management
      interventions for patients with CHF. SEARCH STRATEGY: We searched: Cochrane
      CENTRAL Register of Controlled Trials (to June 2003); MEDLINE (January 1966 to
      July 2003); EMBASE (January 1980 to July 2003); CINAHL (January 1982 to July
      2003); AMED (January 1985 to July 2003); Science Citation Index Expanded
      (searched January 1981 to March 2001); SIGLE (January 1980 to July 2003); DARE
      (July 2003); National Research Register (July 2003); NHS Economic Evaluations
      Database (March 2001); reference lists of articles and asked experts in the
      field. SELECTION CRITERIA: Randomised controlled trials comparing disease
      management interventions specifically directed at patients with CHF to usual
      care. DATA COLLECTION AND ANALYSIS: At least two reviewers independently
      extracted data information and assessed study quality. Study authors were
      contacted for further information where necessary. MAIN RESULTS: Sixteen trials
      involving 1,627 people were included. We classified the interventions into three
      models: multidisciplinary interventions (a holistic approach bridging the gap
      between hospital admission and discharge home delivered by a team); case
      management interventions (intense monitoring of patients following discharge
      often involving telephone follow up and home visits); and clinic interventions
      (follow up in a CHF clinic). There was considerable overlap within these
      categories, however the components, intensity and duration of the interventions
      varied. Case management interventions tended to be associated with reduced all
      cause mortality but these findings were not statistically significant (odds ratio
      0.86, 95% confidence interval 0.67 to 1.10, P = 0.23), although the evidence was
      stronger when analysis was limited to the better quality studies (odds ratio
      0.68, 95% confidence interval 0.46 to 0.98, P = 0.04). There was weak evidence
      that case management interventions may be associated with a reduction in
      admissions for heart failure. It is unclear what the effective components of the
      case management interventions are. The single RCT of a multidisciplinary
      intervention showed reduced heart-failure related re-admissions in the short
      term. At present there is little available evidence to support clinic based
      interventions. AUTHORS' CONCLUSIONS: The data from this review are insufficient
      for forming recommendations. Further research should include adequately powered,
      multi-centre studies. Future studies should also investigate the effect of
      interventions on patients' and carers' quality of life, their satisfaction with
      the interventions and cost effectiveness.

PMID- 15846640
TI  - Corticosteroids for myasthenia gravis.
AB  - BACKGROUND: Although widely accepted as an appropriate immunosuppressive therapy,
      the efficacy of glucocorticosteroid treatment has only rarely been tested in
      controlled studies. OBJECTIVES: To assess the efficacy of glucocorticosteroids or
      adrenocorticotrophic hormone (ACTH) medication in autoimmune myasthenia gravis.
      SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials
      Register in July 2004, MEDLINE (from January 1966 to June 2004) and EMBASE (from
      January 1980 to June 2004). We also checked the bibliographies in reviews and the
      randomised trials and contacted their authors to identify additional published
      and unpublished data. SELECTION CRITERIA: From the articles identified we
      selected those open or controlled studies which allowed us to assess the outcome
      of treated and untreated patients at definite endpoints. Types of studies: quasi
      randomised or randomised controlled trials. TYPES OF PARTICIPANTS: patients with
      myasthenia gravis of all ages and all degrees of severity. Types of
      interventions: any form of glucocorticosteroids or adrenocorticotrophic hormone
      treatment. Types of outcome measures:Primary outcome(1) improvement after at
      least three months in either the weakest muscles or all muscles. Secondary
      outcomes(1) proportion of patients improved after at least six months(2)
      proportion of patients in remission(3) number of episodes of worsening during the
      first six months(4) acetylcholine receptor antibody titres after at least three
      months of therapy. DATA COLLECTION AND ANALYSIS: Three authors extracted the data
      from the selected articles and one other checked them. MAIN RESULTS: A trial of
      adrenocorticotrophic hormone (43 patients) did not show any advantage compared
      with placebo for the treatment of ocular myasthenia gravis. Two double-blind
      trials compared prednisone with placebo for generalised myasthenia gravis. In the
      first (13 patients), the improvement was slightly greater in the prednisone group
      at six months. In the second (20 patients) which was a short-term trial, the
      improvement was significantly greater at two weeks. Two trials compared
      glucocorticosteroids with azathioprine (41 and 10 patients respectively). In one
      of these the rate of treatment failure was greater in the prednisone group. In a
      trial of glucocorticosteroids versus intravenous immunoglobulin (33 patients) no
      differences in treatment responses were encountered during a treatment period of
      14 days. An open trial (39 patients) evaluating different corticosteroid doses
      revealed a shorter time to improvement in the high-dose group. However only
      limited evidence can be drawn from the available randomised controlled trials due
      to numerous and important methodological flaws. AUTHORS' CONCLUSIONS: Limited
      evidence from randomised controlled trials suggests that corticosteroid treatment
      offers significant short-term benefit in myasthenia gravis compared with placebo.
      This supports the conclusions of observational studies and expert opinion.
      Limited evidence from randomised controlled trials does not show any difference
      in efficacy between corticosteroids and either azathioprine or intravenous
      immunoglobulin.

PMID- 15846641
TI  - Prevention of recurrent miscarriage for women with antiphospholipid antibody or
      lupus anticoagulant.
AB  - BACKGROUND: A range of treatments have been proposed to improve pregnancy outcome
      in recurrent pregnancy loss associated with antiphospholipid antibody (APL).
      Small studies have not resolved uncertainty about benefits and risks. OBJECTIVES:
      To examine outcomes of all treatments given to maintain pregnancy in women with
      prior miscarriage and APL. SEARCH STRATEGY: We searched the Pregnancy and
      Childbirth Group's Trials Register (30 May 2004), the Cochrane Central Register
      of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE (1966 to June
      2003), EMBASE (1988 to June 2003), Lupus (volume one to eight, 1991 to 1999) and
      conference proceedings from the International Symposium on APL up to 1999.
      SELECTION CRITERIA: Randomised or quasi-randomised, controlled trials of
      interventions in pregnant women with a history of pregnancy loss and APL. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed quality and
      extracted data for studies up to December 1999. One review author performed this
      for studies after 1999. MAIN RESULTS: Thirteen studies were found (849
      participants). The quality was not high; 50% had clear evidence of allocation
      concealment. Participant characteristics varied between trials. Unfractionated
      heparin combined with aspirin (two trials; n = 140) significantly reduced
      pregnancy loss compared to aspirin alone (relative risk (RR) 0.46, 95% confidence
      interval (CI) 0.29 to 0.71). Low molecular weight heparin (LMWH) combined with
      aspirin compared to aspirin (one trial; n = 98) did not significantly reduce
      pregnancy loss (RR 0.78, 95% CI 0.39 to 1.57). There was no advantage in high
      dose, over low-dose, unfractionated heparin (one trial; n = 50). Three trials of
      aspirin alone (n = 135) showed no significant reduction in pregnancy loss (RR
      1.05, 95% CI 0.66 to 1.68). Prednisone and aspirin (three trials; n = 286)
      resulted in a significant increase in prematurity when compared to placebo,
      aspirin, and heparin combined with aspirin, and an increase in gestational
      diabetes, but no significant benefit. Intravenous immunoglobulin +/-
      unfractionated heparin and aspirin (two trials; n = 58) was associated with an
      increased risk of pregnancy loss or premature birth when compared to
      unfractionated heparin or LMWH combined with aspirin (RR 2.51, 95% CI 1.27 to
      4.95). When compared to prednisone and aspirin, intravenous immunoglobulin (one
      trial; n = 82) was not significantly different in outcomes. AUTHORS' CONCLUSIONS:
      Combined unfractionated heparin and aspirin may reduce pregnancy loss by 54%.
      Large, randomised controlled trials with adequate allocation concealment are
      needed to explore potential differences between unfractionated heparin and LMWH.

PMID- 15846642
TI  - Inhaled tiotropium for stable chronic obstructive pulmonary disease.
AB  - BACKGROUND: Tiotropium is a new anticholinergic therapy for chronic obstructive
      pulmonary disease (COPD) that differs from ipratropium by its functional relative
      selectivity for muscarinic receptor subtypes and which allows once-per-day
      dosing. OBJECTIVES: To determine the efficacy of tiotropium on clinical endpoints
      such exacerbations and hospitalisations, symptom scales and pulmonary function
      compared to placebo and other bronchodilators used for stable COPD. SEARCH
      STRATEGY: Randomised controlled trials (RCTs) were identified from the Cochrane
      Airways Review Group Specialised Register, a compilation of systematic searches
      of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE
      and CINAHL, and hand searching of 20 respiratory journals. Bibliographies from
      included studies and reviews were searched. The date of the last search was
      October 2004. SELECTION CRITERIA: Randomised clinical trials comparing tiotropium
      with placebo, ipratropium bromide, or long-acting ss2-agonists for greater than,
      or equal to, one month's duration. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted data. Missing data were obtained from authors or the
      manufacturer of tiotropium. The data were analysed using the Cochrane Review
      Manager RevMan 4.2. Studies were pooled to yield weighted mean differences (WMD)
      or odds ratios (OR) and reported using 95% confidence intervals (CI). MAIN
      RESULTS: From 69 identified references, nine RCTs (6,584 patients) met inclusion
      criteria. Tiotropium reduced the odds of a COPD exacerbation (OR 0.74; 95% CI
      0.66 to 0.83) and related hospitalisations (OR 0.64; 95% CI 0.51 to 0.82)
      compared to placebo or ipratropium. When applied to an annual baseline risk of
      45% for exacerbations and 10% for hospitalisation, the number of patients needed
      to treat with tiotropium for one year were 14 (95% CI 11 to 22) to prevent one
      exacerbation and 30 (95% CI 22 to 61) to prevent one hospitalisation compared to
      placebo and ipratropium. Reductions in these endpoints compared to long-acting
      ss2-agonists were not statistically significant. Similar patterns were evident
      for quality-of-life and symptom scales. Increases in FEV1 and FVC from baseline
      were significantly larger with tiotropium than with placebo, ipratropium and long
      acting ss2-agonists over 6 to 12 months. The decline in trough FEV1 from steady
      state was 30 ml (95% CI 7 to 53 ml) less with tiotropium than with placebo or
      ipratropium over one year; no data on decline in FEV1 from steady state were
      available for long-acting ss2-agonists. Dry mouth was increased by tiotropium.
      AUTHORS' CONCLUSIONS: Tiotropium reduced COPD exacerbations and related
      hospitalisations compared to placebo and ipratropium. It also improved health
      related quality-of-life and symptom scores among patients with moderate and
      severe disease, and may have slowed decline in FEV1. Additional long-term studies
      are required to evaluate its effect on mortality and change in FEV1 to clarify
      its role in comparison to, or in combination with, long-acting ss2-agonists and
      to assess its effectiveness in mild and very severe COPD.

PMID- 15846643
TI  - Alarm interventions for nocturnal enuresis in children.
AB  - BACKGROUND: Enuresis (bedwetting) is a socially disruptive and stressful
      condition which affects around 15 to 20% of five year olds, and up to 2% of young
      adults. OBJECTIVES: To assess the effects of alarm interventions on nocturnal
      enuresis in children, and to compare alarms with other interventions. SEARCH
      STRATEGY: We searched the Cochrane Incontinence Group specialised trials register
      (searched 22 November 2004) and the reference lists of relevant articles.
      SELECTION CRITERIA: All randomised or quasi-randomised trials of alarm
      interventions for nocturnal enuresis in children were included, except those
      focused solely on daytime wetting. Comparison interventions included no
      treatment, simple and complex behavioural methods, desmopressin, tricyclics, and
      miscellaneous other methods. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed the quality of the eligible trials, and extracted data.
      MAIN RESULTS: Fifty five trials met the inclusion criteria, involving 3152
      children of whom 2345 used an alarm. The quality of many trials was poor, and
      evidence for many comparisons was inadequate. Most alarms used audio methods.
      Compared to no treatment, about two thirds of children became dry during alarm
      use (RR for failure 0.38, 95% CI 0.33 to 0.45). Nearly half who persisted with
      alarm use remained dry after treatment finished, compared to almost none after no
      treatment (RR of failure or relapse 45/81 (55%) vs 80/81 (99%), RR 0.56, 95% CI
      0.46 to 0.68). There was insufficient evidence to draw conclusions about
      different types of alarm, or about how alarms compare to other behavioural
      interventions. Relapse rates were lower when overlearning was added to alarm
      treatment (RR 1.92, 95% CI 1.27 to 2.92) or if dry bed training was used as well
      (RR 2.0, 95% CI 1.25 to 3.20). Penalties for wet beds appeared to be counter
      productive. Alarms using electric shocks were unacceptable to children or their
      parents. Although desmopressin may have a more immediate effect, alarms appear
      more effective by the end of a course of treatment (RR 0.71, 95% CI 0.50 to 0.99)
      and there was limited evidence of greater long-term success (4/22 (18%) vs 16/24
      (67%), RR 0.27, 95% CI 0.11 to 0.69). Evidence about the benefit of supplementing
      alarm treatment with desmopressin was conflicting. Alarms were better than
      tricyclics during treatment (RR 0.73, 95% CI 0.61 to 0.88) and afterwards (7/12
      (58%) vs 12/12 (100%), RR 0.58, 95% CI 0.36 to 0.94). AUTHORS' CONCLUSIONS: Alarm
      interventions are an effective treatment for nocturnal bedwetting in children.
      Alarms appear more effective than desmopressin or tricyclics by the end of
      treatment, and subsequently. Overlearning (giving extra fluids at bedtime after
      successfully becoming dry using an alarm), dry bed training and avoiding
      penalties may further reduce the relapse rate. Better quality research comparing
      alarms with other treatments is needed, including follow-up to determine relapse
      rates.

PMID- 15846644
TI  - Interventions for treating posterior cruciate ligament injuries of the knee in
      adults.
AB  - BACKGROUND: Injuries of the posterior cruciate ligament (PCL) of the knee
      frequently occur in automobile accidents and sports injuries, although they are
      less frequent overall than injuries of the anterior cruciate ligament (ACL). Some
      patients show significant symptoms and subsequent articular deterioration, while
      others are essentially asymptomatic, maintaining habitual function. Management of
      PCL injuries remains controversial and prognosis can vary widely. Interventions
      extend from non-operative (conservative) procedures to reconstruction of the PCL,
      in the hope that the surgical procedure may have a positive effect in the
      reduction/prevention of future osteoarthritic changes in the knee. OBJECTIVES: To
      determine the effectiveness and safety of surgical and conservative interventions
      for PCL injuries in adults. SEARCH STRATEGY: We searched the Cochrane
      Musculoskeletal Injuries Group Specialised Register (April 2004), the Cochrane
      Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004),
      MEDLINE via PubMed (1966 to April 2004), EMBASE (1966 to April 2004), CINAHL
      (1982 to April 2004), LILACS (1982 to April 2004), SportsDiscus (1975 to April
      2004), and reference lists of articles. SELECTION CRITERIA: Randomized or quasi
      randomized clinical trials comparing various methods of operative and
      conservative interventions, and comparisons with each other for the treatment of
      PCL injuries. DATA COLLECTION AND ANALYSIS: References found with the search
      strategy were evaluated independently by two review authors. MAIN RESULTS: No
      randomized or quasi-randomized controlled studies meeting the selection criteria
      were identified. AUTHORS' CONCLUSIONS: Future research should include randomized
      controlled trials of acute isolated PCL injuries, or PCL injuries when combined
      with other ligament injuries of the knee, treated operatively and conservatively.
      Adequate numbers of patients and an objective methodology for patient evaluation
      must be used in future studies of these interventions to determine the long-term
      results.

PMID- 15846645
TI  - Glucosamine therapy for treating osteoarthritis.
AB  - BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis, and it is
      often associated with significant disability and an impaired quality of life.
      OBJECTIVES: To review all randomized controlled trials (RCTs) evaluating the
      effectiveness and toxicity of glucosamine in OA. SEARCH STRATEGY: We searched
      MEDLINE, PREMEDLINE, EMBASE, AMED, ACP Journal Club, DARE, CDSR, and the CCTR. We
      also wrote letters to content experts, and hand searched reference lists of
      identified RCTs and pertinent review articles. All searches were updated in
      January 2005. SELECTION CRITERIA: Relevant studies met the following criteria: 1)
      RCTs evaluating the effectiveness and safety of glucosamine in OA, 2) Both
      placebo controlled and comparative studies were eligible, 3) Both single blinded
      and double blinded studies were eligible. DATA COLLECTION AND ANALYSIS: Data
      abstraction was performed independently by two investigators and the results were
      compared for degree of agreement. Gotzsche's method and a validated tool (Jadad
      1996) were used to score the quality of the RCTs. Continuous outcome measures
      were pooled using standardized mean differences (SMD) as the measure of effect
      size. Dichotomous outcome measures were pooled using relative risk ratios (RR).
      MAIN RESULTS: Analysis restricted to eight studies with adequate allocation
      concealment failed to show benefit of glucosamine for pain and WOMAC function.
      Collectively, the 20 analyzed RCTs found glucosamine favoured placebo with a 28%
      (change from baseline) improvement in pain (SMD -0.61, 95% CI -0.95, -0.28) and a
      21% (change from baseline) improvement in function using the Lequesne index (SMD 
      0.51 95% CI -0.96, -0.05). However, the results are not uniformly positive, and
      the reasons for this remain unexplained. WOMAC pain, function and stiffness
      outcomes did not reach statistical significance. In the 10 RCTs in which the
      Rotta preparation of glucosamine was compared to placebo, glucosamine was found
      to be superior for pain (SMD -1.31, 95% CI -1.99, -0.64) and function using the
      Lequesne index (SMD -0.51, 95% CI -0.96, -0.05). Pooled results for pain (SMD 
      0.15, 95% CI -0.35, 0.05) and function using the WOMAC index (SMD 0.03, 95% CI 
      0.18, 0.25) in those RCTs in which a non-Rotta preparation of glucosamine was
      compared to placebo did not reach statistical significance. In the four RCTs in
      which the Rotta preparation of glucosamine was compared to an NSAID, glucosamine
      was superior in two, and equivalent in two. Two RCTs using the Rotta preparation
      showed that glucosamine was able to slow radiological progression of OA of the
      knee over a three year period (SMD 0.24, 95% CI 0.04, 0.43). Glucosamine was as
      safe as placebo in terms of the number of subjects reporting adverse reactions
      (RR=0.97, 95% CI, 0.88, 1.08). AUTHORS' CONCLUSIONS: This update includes 20
      studies with 2570 patients. Pooled results from studies using a non-Rotta
      preparation or adequate allocation concealment failed to show benefit in pain and
      WOMAC function while those studies evaluating the Rotta preparation show that
      glucosamine was superior to placebo in the treatment of pain and functional
      impairment resulting from symptomatic OA. WOMAC outcomes of pain, stiffness and
      function did not show a superiority of glucosamine over placebo for both Rotta
      and non-Rotta preparations of glucosamine. Glucosamine was as safe as placebo.

PMID- 15846646
TI  - Prostacyclin for pulmonary hypertension in adults.
AB  - BACKGROUND: Primary pulmonary hypertension (PPH) is progressive, resulting in
      right ventricular failure. Pulmonary hypertension can be idiopathic or associated
      with other conditions. Prostacyclin is a potent vasodilator and inhibitor of
      platelet aggregation, and can be given orally, subcutaneously, intravenously or
      inhaled via a nebuliser. OBJECTIVES: To determine the efficacy of prostacyclin or
      one of its analogues in idiopathic primary pulmonary hypertension. SEARCH
      STRATEGY: Electronic searches were carried out with pre-specified terms. Searches
      were current as of July 2004. SELECTION CRITERIA: Two reviewers selected
      randomised controlled trials (RCTs) involving adults with pulmonary hypertension
      for inclusion. DATA COLLECTION AND ANALYSIS: Study quality was assessed and data
      extracted independently by two reviewers. Outcomes were analysed as continuous
      and dichotomous outcomes. We sub-grouped data where possible by aetiology of PH
      (PPH, PH secondary to connective tissue disorder or mixed populations). MAIN
      RESULTS: Nine RCTs of mixed duration (3 days-52 weeks), recruiting 1175
      participants were included (NYHA functional classes II-IV). Intravenous
      prostacyclin versus usual care (four studies): There were significant
      improvements in exercise capacity of around 90 metres, cardiopulmonary
      haemodynamics and NYHA functional class over 3 days-12 weeks. Effects were
      consistent in primary and secondary pulmonary hypertension. Oral prostacyclin
      versus placebo (two studies): Short-term data (3-6 months) indicated that there
      was a significant improvement in exercise capacity, but data from one study of 52
      weeks reported no significant difference at 12 months. No significant differences
      were observed for any other outcome. Subcutaneous treprostinil versus placebo
      (two studies, 8-12 weeks):One large study reported a significant median
      improvement in exercise capacity of around 16 metres. Cardiopulmonary
      haemodynamics and symptom scores favoured treprostinil. Infusion site pain and
      withdrawals due to adverse events were more frequent with treprostinil. Inhaled
      prostacyclin versus placebo (one study, 12 weeks):There was a significant
      increase in exercise capacity of approximately 36 metres. Treatment led to better
      symptom scores and functional class status than with placebo. Subgroup analyses
      reported by individual studies showed a better exercise capacity in participants
      with PPH, than those participants with PH secondary to other diseases. Side
      effects and adverse events were common in the studies. AUTHORS' CONCLUSIONS:
      There is evidence that intravenous prostacyclin in addition to conventional
      therapy at tolerable doses optimised by titration, can confer some short-term
      benefits (up to 12 weeks of treatment) in exercise capacity, NYHA functional
      class and cardiopulmonary haemodynamics. There is also some evidence that
      patients with more severe disease based upon NYHA functional class showed a
      greater response to treatment.

PMID- 15846647
TI  - School-based prevention for illicit drugs' use.
AB  - BACKGROUND: Drug addiction is a chronic, relapsing disease. Primary interventions
      should be aimed to reduce first use, or prevent the transition from experimental
      use to addiction. School is the appropriate setting for preventive interventions.
      OBJECTIVES: To evaluate the effectiveness of school-based interventions in
      improving knowledge, developing skills, promoting change, and preventing or
      reducing drug use versus usual curricular activities or a different school-based
      intervention . SEARCH STRATEGY: MEDLINE , EMBASE, ERIC, PSYCHINFO, Cochrane
      Library, ACP Journal Club, Cochrane Drug and Alcohol Group Register, updated to
      February 2004, were searched. Bibliography of papers was checked and personal
      contacts were made to identify other relevant studies. SELECTION CRITERIA: RCTs,
      CCTs or Controlled Prospective Studies (CPS) evaluating school-based
      interventions designed to prevent substance use. DATA COLLECTION AND ANALYSIS:
      Data were selected and extracted independently by two reviewers. Quality was
      assessed with the CDAG checklist. Interventions were classified as skills,
      affective, knowledge-focused and other characteristics were also studied
      (teaching, follow-up implementation, context activation). MAIN RESULTS: 32
      studies (29 RCTs and 3 CPSs) were included. 28 were conducted in the USA; most
      were focused on 6th-7th grade students, and based on post-test assessment. RCTs:
      (1) Knowledge vs usual curricula: Knowledge focused programs improve drug
      knowledge (SMD=0.91; 95% CI: 0.42, 1.39).(2) Skills vs usual curricula: Skills
      based interventions increase drug knowledge (WMD=2.60; 95% CI: 1.17-4.03),
      decision making skills (SMD=0.78; CI95%: 0.46-1.09), self-esteem (SMD=0.22;
      CI95%: 0.03-0.40), peer pressure resistance (RR=2.05; CI95%: 1.24-3.42), drug use
      (RR=0.81; CI95%: 0.64, 1.02), marijuana use (RR=0.82; CI95%: 0.73, 0.92) and hard
      drug use (RR=0.45; CI95%: 0.24-0.85). (3) Skills vs knowledge: No differences are
      evident.(4) Skills vs affective: Skills-based interventions are only better than
      affective ones in self-efficacy (WMD=1.90; CI95%: 0.25, 3.55). (5) Affective vs
      usual curricula: Affective interventions improve drug knowledge (SMD=1.88; CI95%:
      1.27, 2.50) and decision making skills (SMD=1.35; CI95%: 0.79, 1.9). (6)
      Affective vs knowledge: Affective interventions improve drug knowledge (SMD=0.60;
      CI95%: 0.18,1.03), and decision making skills (SMD=1.22; CI95%: 0.33, 2.12).
      Results from CPSs: No statistically significant results emerge from CPSs.
      AUTHORS' CONCLUSIONS: Skills based programs appear to be effective in deterring
      early-stage drug use. The replication of results with well designed, long term
      randomised trials, and the evaluation of single components of intervention (peer,
      parents, booster sessions) are the priorities for research. All new studies
      should control for cluster effect.

PMID- 15846648
TI  - Benperidol for schizophrenia.
AB  - BACKGROUND: Benperidol is a relatively old antipsychotic drug that has been
      marketed since 1966. It has been used in Germany for 30 years, but is also
      available in Belgium, Greece, Italy, the Netherlands and the UK. Benperidol is a
      butyrophenone antipsychotic, with the highest neuroleptic potency in terms of D2
      receptor blockade. Those taking it are therefore reputed to be at high risk of
      extrapyramidal side effects, but benperidol's unusual profile may render it
      valuable to subgroups of people with schizophrenia. OBJECTIVES: To examine the
      clinical effects and safety of benperidol for those with schizophrenia and
      schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane
      Schizophrenia Group's register (November 2004) for this update. SELECTION
      CRITERIA: We included all randomised controlled trials that compared benperidol
      with other treatments for people with schizophrenia, or schizophrenia-like
      psychoses. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality
      rated them and extracted data. We independently extracted data but excluded data
      if loss to follow up was greater than 50%. For dichotomous data, we estimated
      relative risks (RR), with the 95% confidence intervals (CI). Where possible, we
      calculated the number needed to treat/harm statistic (NNT/H) and used intention
      to-treat analysis. MAIN RESULTS: The update yielded no further studies for
      inclusion in the review. We identified only one unpublished poorly randomised
      controlled trial (N=40, duration 30 days, comparison perphenazine). Although
      benperidol was inferior to perphenazine (1 RCT, N=40, global state no better or
      worse RR 8.0 CI 2.1 to 30, NNH 1.4 CI 1 to 2) poor reporting suggests that an
      overestimate of effect is likely. It was not possible to report other outcomes.
      AUTHORS' CONCLUSIONS: Currently, there are insufficient data from randomised
      trials to assess the clinical effects of benperidol. This compound merits further
      research interest.

PMID- 15846649
TI  - Inhaled fluticasone versus placebo for chronic asthma in adults and children.
AB  - BACKGROUND: Inhaled fluticasone propionate (FP) is a relatively new inhaled
      corticosteroid for the treatment of asthma. OBJECTIVES: 1. To assess efficacy and
      safety outcomes in studies that compared FP to placebo for treatment of chronic
      asthma.2. To explore the presence of a dose-response effect. SEARCH STRATEGY: We
      searched the Cochrane Airways Group Trial Register (January 2004), reference
      lists of articles, contacted trialists and searched abstracts of major
      respiratory society meetings (1997-2004). SELECTION CRITERIA: Randomised trials
      in children and adults comparing FP to placebo in the treatment of chronic
      asthma. Two reviewers independently assessed articles for inclusion and
      methodological quality. DATA COLLECTION AND ANALYSIS: Two reviewers extracted
      data. Quantitative analyses where undertaken using RevMan Analyses 4.2.7. MAIN
      RESULTS: Sixty eight studies met the inclusion criteria (11, 104 participants).
      Methodological quality was high. In non-oral steroid treated asthmatics with mild
      and moderate disease FP resulted in improvements from baseline compared with
      placebo across all dose ranges (100 to 1000 mcg/d) in FEV1 (between 0.13 to 0.45
      litres); morning PEF (between 27 and 47 L/min); symptom scores (based on a
      standardised scale, between 0.5 and 0.85); reduction in rescue beta-2 agonist use
      (between 1.2 and 2.2 puffs/d). High dose FP reduced the number of patients
      dependent on prednisolone: FP 1000-1500 mcg/d Peto Odds Ratio 0.07 (95% CI 0.05
      to 0.10). FP at all doses led to a greater likelihood of sore throat, hoarseness
      and oral Candidiasis, but 21 patients would need to be treated for one extra to
      develop Candidiasis (FP 500 mcg/day), whilst only three or four patients need to
      be treated to avoid one extra patient being withdrawn due to lack of efficacy at
      all doses of FP. AUTHORS' CONCLUSIONS: Doses of FP in the range 100-1000 mcg/d
      are effective. In most patients with mild-moderate asthma improvements with low
      dose FP are only a little less than those associated with high doses when
      compared with placebo. High dose FP appears to have worthwhile oral
      corticosteroid reducing properties. FP use is accompanied by an increased
      likelihood of oropharyngeal side effects.

PMID- 15846650
TI  - Memantine for dementia.
AB  - BACKGROUND: Memantine, a low affinity antagonist to glutamate NMDA receptors, may
      prevent excitatory neurotoxicity in dementia. OBJECTIVES: To determine efficacy
      and safety of memantine for people with Alzheimer's disease (AD), vascular (VD)
      and mixed dementia. SEARCH STRATEGY: The Specialized Register of the Cochrane
      Dementia and Cognitive Improvement Group was searched on 28 October 2004. This
      register contains references from all major healthcare databases and many ongoing
      trial databases and is updated regularly. In addition the search engines Copernic
      and Google were used to identify unpublished trials through inspection of the
      websites of licensing bodies like the FDA , EMEA an Nice and of companies'
      websites (Lundbeck, Merz, Forest, Suntori etc). SELECTION CRITERIA: Double-blind,
      parallel group, placebo-controlled, randomized trials of memantine in people with
      dementia. DATA COLLECTION AND ANALYSIS: Data were pooled where possible.
      Intention-to-treat (ITT) and observed case (OC) analyses are reported. MAIN
      RESULTS: 1. Moderate to severe AD. A major study (MD-01) is unpublished.
      Published data from two six month studies show a small beneficial effect of
      memantine at six months on cognition (4.12 SIB points, 95% Confidence Interval
      (CI) 2.14 to 5.74, P < 0.00001), activities of daily living (1.70 ADCS-ADLsev19
      points, 95% CI 0.63 to 2.76, p = 0.002) and behaviour (3.64 NPI points, 95% CI
      1.38 to 5.90, p = 0.002), supported by clinical impression of change (0.27 CIBIC+
      points, 95% CI 0.10 to 0.43, p = 0.002). The unpublished study would need to have
      found a detrimental effect of memantine to overturn the statistical significance
      of the benefits apparent in the two published studies. 2. Mild to moderate AD. In
      a single six month trial, memantine had a beneficial effect on ITT analysis of
      cognition, (1.9 ADAS-Cog points, 95% CI 0.35 to 3.43, p = 0.02) and behaviour
      (3.50 NPI points 95% CI 0.15 to 6.85, p = 0.04) supported by clinical global
      impression of change (0.30 CIBIC+ points, 95% CI 0.09 to 0.51, p = 0.005), but no
      effect on activities of daily living or OC analysis of cognition. The statistical
      significance of these benefits could be overturned by data from two unpublished
      studies which are known to show no significant effect. 3. Mild to moderate
      vascular dementia. In two six month studies, memantine improved cognition (1.85
      ADAS-Cog points, 95% CI 0.88 to 2.83, p = 0.0002), and behaviour (Weighted Mean
      Difference (WMD) 0.84 95% CI 0.06 to 0.91, p = 0.03) but this was not supported
      by clinical global measures.4. Patients taking memantine were less likely to
      develop agitation (Odds Ratio (OR): 0.65, 95% CI 0.48 to 0.89, p = 0.007). The
      effect on agitation which is already present is unknown.5. Memantine is well
      tolerated. AUTHORS' CONCLUSIONS: Published data suggest a small beneficial effect
      of memantine at six months in moderate to severe AD. The beneficial effect on
      cognition in patients with mild to moderate vascular dementia was not clinically
      discernible at six months. Whether memantine has any effect in mild to moderate
      AD is unknown.

PMID- 15846651
TI  - Base administration or fluid bolus for preventing morbidity and mortality in
      preterm infants with metabolic acidosis.
AB  - BACKGROUND: Metabolic acidosis in the early newborn period is associated with
      adverse outcomes in preterm infants. The most commonly used strategies to correct
      metabolic acidosis are intravascular infusion of base, for example sodium
      bicarbonate, and intravascular infusion of a fluid bolus, usually a crystalloid
      or colloid solution. OBJECTIVES: To evaluate the available evidence from
      randomised controlled trials that either infusion of base, or of a fluid bolus,
      reduces mortality and adverse neurodevelopmental outcomes in preterm infants with
      metabolic acidosis. SEARCH STRATEGY: We used the standard search strategy of the
      Cochrane Neonatal Review Group. This included searches of the Cochrane Central
      Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005),
      MEDLINE (1966 - January 2005), EMBASE (1980 - January 2005), CINAHL (1982 -
      January 2005). SELECTION CRITERIA: Randomised or quasi-randomised controlled
      trials that evaluated the following treatments for preterm infants with metabolic
      acidosis:1. Infusion of base versus no treatment.2. Infusion of fluid bolus
      versus no treatment.3. Infusion of base versus fluid bolus. DATA COLLECTION AND
      ANALYSIS: We extracted the data using the standard methods of the Cochrane
      Neonatal Review Group, with separate evaluation of trial quality and data
      extraction by two authors, and synthesis of data using relative risk and risk
      difference. MAIN RESULTS: We found two small randomised controlled trails that
      fulfilled the eligibility criteria (Corbet 1977; Dixon 1999). Corbet 1977
      compared treating infants with sodium bicarbonate infusion (N = 30) versus no
      treatment (N = 32) and did not find evidence of an effect on mortality [Relative
      risk 1.39 (95% confidence interval 0.72 to 2.67), risk difference 0.12 (95%
      confidence interval -0.12 to 0.36)], or in the incidence of intra/peri
      ventricular haemorrhage [Relative risk 1.24 (95% confidence interval 0.47 to
      3.28), risk difference 0.05 (95% confidence interval -0.16 to 0.25)]. Dixon 1999
      compared treatment with sodium bicarbonate (N = 16) versus fluid bolus (N = 20).
      The primary outcome assessed was arterial blood pH/base excess two hours after
      the intervention. Other clinical outcomes were not reported. Neither trial
      assessed longer term neurodevelopmental outcomes. AUTHORS' CONCLUSIONS: There is
      insufficient evidence from randomised controlled trials to determine whether
      infusion of base or fluid bolus reduces morbidity and mortality in preterm
      infants with metabolic acidosis. Further large randomised trials are needed.

PMID- 15846652
TI  - Emergency interventions for hyperkalaemia.
AB  - BACKGROUND: Hyperkalaemia occurs in outpatients and in between 1% and 10% of
      hospitalised patients. When severe, consequences include arrhythmia and death.
      OBJECTIVES: To review randomised evidence informing the emergency (i.e. acute,
      rather than chronic) management of hyperkalaemia SEARCH STRATEGY: We searched
      MEDLINE (1966-2003), EMBASE (1980-2003), The Cochrane Library (issue 4, 2003),
      and SciSearch using the text words hyperkal* or hyperpotass* (* indicates
      truncation). We also searched selected journals and abstracts of meetings. The
      reference lists of recent review articles, textbooks, and relevant papers were
      reviewed for additional potentially relevant titles. SELECTION CRITERIA: All
      selection was performed in duplicate. Articles were considered relevant if they
      were randomised, quasi-randomised or cross-over randomised studies of
      pharmacological or other interventions to treat non-neonatal humans with
      hyperkalaemia, reporting on clinically-important outcomes, or serum potassium
      levels within the first six hours of administration. DATA COLLECTION AND
      ANALYSIS: All data extraction was performed in duplicate. We extracted quality
      information, and details of the patient population, intervention, baseline and
      follow-up potassium values. We extracted information about arrhythmias, mortality
      and adverse effects. Where possible, meta-analysis was performed using random
      effects models. MAIN RESULTS: None of the studies of clinically-relevant
      hyperkalaemia reported mortality or cardiac arrhythmias. Reports focussed on
      serum potassium levels. Many studies were small, and not all intervention groups
      had sufficient data for meta-analysis to be performed. On the basis of small
      studies, inhaled beta-agonists, nebulised beta-agonists, and intravenous (IV)
      insulin-and-glucose were all effective, and the combination of nebulised beta
      agonists with IV insulin-and-glucose was more effective than either alone.
      Dialysis is effective. Results were equivocal for IV bicarbonate. K-absorbing
      resin was not effective by four hours, and longer follow up data on this
      intervention were not available from RCTs. AUTHORS' CONCLUSIONS: Nebulised or
      inhaled salbutamol, or IV insulin-and-glucose are the first-line therapies for
      the management of emergency hyperkalaemia that are best supported by the
      evidence. Their combination may be more effective than either alone, and should
      be considered when hyperkalaemia is severe. When arrhythmias are present, a
      wealth of anecdotal and animal data suggests that IV calcium is effective in
      treating arrhythmia. Further studies of the optimal use of combination treatments
      and of the adverse effects of treatments are needed.

PMID- 15846653
TI  - Medical treatments for the maintenance therapy of reflux oesophagitis and
      endoscopic negative reflux disease.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GORD) - reflux of stomach contents
      +/- bile into the oesophagus causing symptoms such as heartburn and acid reflux -
      is a common relapsing and remitting disease which often requires long-term
      maintenance therapy. Patients with GORD may have oesophagitis (inflammation of
      the oesophagus) or a normal endoscopy (endoscopy negative reflux disease or
      ENRD). OBJECTIVES: To assess the effects of continuous maintenance therapy in
      adults with GORD (both ENRD and healed oesophagitis). SEARCH STRATEGY: We
      searched Cochrane Central Register of Controlled Trials (The Cochrane Library
      Issue 2, 2003), MEDLINE (1966 to 2003), EMBASE (1980 to 2003), CINAHL (1982
      2003), and the National Research Register (Issue 2, 2003) and reference lists of
      articles. We also contacted manufacturers and researchers in the field. SELECTION
      CRITERIA: Randomised controlled studies comparing PPIs, H2RAs, prokinetics,
      sucralfate and combinations either in comparison to another treatment regimen or
      to placebo in adults with reflux oesophagitis and ENRD. DATA COLLECTION AND
      ANALYSIS: One author extracted data from included trials and a second author
      carried out an unblinded check. Two authors independently assessed trial quality.
      Study authors were contacted for additional information. MAIN RESULTS:
      Maintenance of patients with healed oesophagitis: For a healing dose of PPI
      (generally the standard dose given by the manufacturer) versus placebo, the
      relative risk (RR) for oesophagitis relapse was 0.26 (95% confidence interval
      (CI) 0.19 to 0.36); versus H2RAs the RR was 0.36 (95% CI 0.28 to 0.46) and versus
      maintenance PPIs the RR was 0.63 (95% CI 0.55 to 0.73). However overall adverse
      effects were also more common and headaches were more common when comparing
      healing PPIs to H2RAs. For a maintenance dose of PPI (half of the standard dose)
      versus placebo, the RR for oesophagitis relapse was 0.46 (95% CI 0.38 to 0.57)
      and versus H2RAs the RR was 0.57 (95% CI 0.47 to 0.69). Overall adverse effects
      were more common.H2RAs were of marginal help but beneficial for symptomatic
      relief. Prokinetics and sucralfate were also more effective than placebo. For
      ENRD patients: Limited data with one RCT showed benefit for omeprazole 10 mg once
      daily over placebo (RR 0.4; 95% CI 0.29 to 0.53). AUTHORS' CONCLUSIONS: The
      findings in this review support the long-term treatment of oesophagitis to
      prevent relapse, both endoscopically and symptomatically. Healing doses of PPIs
      are more effective than all other therapies, although there is an increase in
      overall adverse effects compared to placebo, and headache occurrence compared to
      H2RAs. H2RAs prevent relapse more effectively than placebo, demonstrating a role
      for PPI-intolerant patients. Prokinetics and sucralfate both show benefit over
      placebo, but the former is no longer licenced. There is only limited data for
      ENRD.

PMID- 15846654
TI  - Treatment for Lambert-Eaton myasthenic syndrome.
AB  - BACKGROUND: Lambert-Eaton myasthenic syndrome is an autoimmune presynaptic
      disorder of neuromuscular transmission. Treatments attempt to overcome the
      harmful autoimmune process, or to improve residual neuromuscular transmission, in
      order to reverse muscle weakness. OBJECTIVES: The objective was to examine the
      efficacy of treatment in Lambert-Eaton myasthenic syndrome. SEARCH STRATEGY: We
      searched the Cochrane Neuromuscular Disease Group trials register (December
      2004), MEDLINE (January 1966 to December 2004) and EMBASE (January 1980 to
      December 2004), and checked bibliographies and contacted authors to identify
      additional published or unpublished data. SELECTION CRITERIA: All randomised or
      quasi-randomised trials of adults and children with a diagnosis of Lambert-Eaton
      myasthenic syndrome, with or without small-cell lung cancer, receiving any form
      of pharmacological or physical treatment. The primary outcome measure was change
      in muscle strength scale score (Quantitative Myasthenia Gravis score), or limb
      muscle strength measured by myometry. The secondary outcome measure was
      improvement in the mean amplitude of the resting compound muscle action
      potentials. The mean amplitude used was the mean of all muscles tested. DATA
      COLLECTION AND ANALYSIS: We identified three randomised controlled trials. MAIN
      RESULTS: Two controlled trials of the effects of 3,4-diaminopyridine compared
      with placebo in a total of 38 patients with Lambert-Eaton myasthenic syndrome
      were eligible, one of which was of crossover design. A third crossover trial
      compared intravenous immunoglobulin treatment to placebo in nine patients. Two
      trials of 3,4-diaminopyridine reported a significant improvement in muscle
      strength score, or myometric limb measurement following treatment, and a
      significant improvement in resting compound muscle action potential amplitude
      following 3,4-diaminopyridine, compared with placebo.A meta-analysis of the
      primary endpoint results was not possible because of marked differences in
      primary outcome measures. However, a meta-analysis of the secondary endpoint was
      possible. The overall weighted mean difference was 1.80 mV (95% confidence
      interval 0.82 to 2.78), favouring treatment.A crossover trial reported a
      significant improvement in myometric limb strength and a non-significant
      improvement in change in the mean resting compound muscle action potential
      amplitude when patients received intravenous immunoglobulin compared to placebo
      infusions. Clinical improvement lasted for up to eight weeks. AUTHORS'
      CONCLUSIONS: Limited evidence from randomised controlled trials showed that
      either 3,4-diaminopyridine or intravenous immunoglobulin improved muscle strength
      scores and compound muscle action potential amplitudes in patients with Lambert
      Eaton myasthenic syndrome. There are insufficient data at present to quantify
      this treatment effect. Other possible treatments have not been tested in
      randomised controlled trials.

PMID- 15846655
TI  - Protein and energy supplementation in elderly people at risk from malnutrition.
AB  - BACKGROUND: Evidence for the effectiveness of nutritional supplements containing
      protein and energy, which are often prescribed for older people, is limited.
      Furthermore malnutrition is more common in this age group and deterioration of
      nutritional status can occur during illness. It is important to establish whether
      supplementing the diet is an effective way of improving outcomes for older people
      at risk from malnutrition. OBJECTIVES: This review examined the evidence from
      trials for improvement in nutritional status and clinical outcomes when extra
      protein and energy were provided, usually in the form of commercial 'sip-feeds'.
      SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, Healthstar, CINAHL, BIOSIS, CAB abstracts. We also
      hand searched nutrition journals and reference lists and contacted 'sip-feed'
      manufacturers. Date of most recent search: March 2004. SELECTION CRITERIA:
      Randomised controlled trials and quasi-randomised controlled trials of oral
      protein and energy supplementation in older people with the exception of groups
      recovering from cancer treatment or in critical care. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently assessed trials prior to inclusion and
      independently extracted data and assessed trial quality. Authors of trials were
      contacted for further information as necessary. MAIN RESULTS: Forty-nine trials
      with 4790 randomised participants have been included in the review. Most included
      trials had poor study quality. The pooled weighted mean difference [WMD] for
      percentage weight change showed a benefit of supplementation of 2.3% (95%
      confidence interval (CI) 1.9 to 2.7) from 34 trials. There was a reduced
      mortality in the supplemented compared with control groups (relative risk (RR)
      0.74, CI 0.59 to 0.92) from 32 trials. The risk of complications from 14 trials
      showed no significant difference (RR 0.95, 95% CI 0.81 to 1.11). Few trials were
      able to suggest any functional benefit from supplementation. The pooled weighted
      mean difference (WMD) for length of stay from 10 trials also showed no
      statistically significant effect (WMD -1.98 days, 95% CI -5.20 to 1.24). AUTHORS'
      CONCLUSIONS: Supplementation produces a small but consistent weight gain in older
      people. There may also be a beneficial effect on mortality. However, there was no
      evidence of improvement in clinical outcome, functional benefit or reduction in
      length of hospital stay with supplements. Additional data from large-scale multi
      centre trials are still required.

PMID- 15846656
TI  - Laryngeal mask airway versus bag-mask ventilation or endotracheal intubation for
      neonatal resuscitation.
AB  - BACKGROUND: Providing effective positive pressure ventilation is the single most
      important component of successful neonatal resuscitation. Ventilation is
      frequently initiated with a manual resuscitation bag and face-mask (BMV) followed
      by endotracheal intubation (ETT) if depression continues. These techniques may be
      difficult to perform successfully resulting in prolonged resuscitation or severe
      neonatal depression. The laryngeal mask airway (LMA) may achieve initial
      ventilation and successful resuscitation faster than a bag-mask device or
      endotracheal intubation. OBJECTIVES: Among newborns requiring positive pressure
      ventilation for resuscitation, is effective ventilation and successful
      resuscitation achieved faster with the LMA compared with either BMV or ETT?
      SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library, Issue 3, 2004), MEDLINE (1966-November 2004), Pre-MEDLINE
      (November 15, 2004), CINAHL 1982-November 2004), reference lists of published
      trials, and Society for Pediatric Research abstracts were searched. Experts were
      contacted for additional references. SELECTION CRITERIA: Randomised and quasi
      randomised trials DATA COLLECTION AND ANALYSIS: Two reviewers independently
      evaluated studies, assessed methodologic quality, and extracted data using the
      Cochrane Neonatal Review Group criteria. Categorical treatment effects were
      described as relative risks and risk differences and continuous treatment effects
      were described as the mean difference. There were insufficient data to perform
      pooled analyses. MAIN RESULTS: No eligible studies compared the LMA with BMV. One
      small randomised controlled trial comparing the LMA with ETT when BMV had been
      unsuccessful was included. There was no statistically significant difference
      between the LMA and ETT with the exception of a clinically insignificant
      difference in time to complete insertion of the device favouring the ETT.
      AUTHORS' CONCLUSIONS: The LMA can achieve effective ventilation during neonatal
      resuscitation in a time-frame consistent with current guidelines. There is no
      evidence to evaluate the relative efficacy and safety of the LMA compared with
      BMV as the primary airway device. A single, small randomised controlled trial
      found no clinically significant difference between the LMA and ETT when BMV was
      unsuccessful. Case series and case reports suggest that the LMA can provide an
      effective rescue airway during resuscitation if both BMV and ETT have been
      unsuccessful. A well-designed randomised controlled trial comparing the LMA with
      BMV during neonatal resuscitation is warranted.

PMID- 15846657
TI  - Acupuncture for acute stroke.
AB  - BACKGROUND: Acupuncture-like sensory stimulation activates multiple efferent
      (nerve) pathways leading to altered activity in numerous neural systems.
      Acupuncture is widely accepted by Chinese people and it is increasingly requested
      by patients and their relatives in Western countries. OBJECTIVES: To assess the
      effectiveness and safety of acupuncture in patients with acute stroke. SEARCH
      STRATEGY: We searched the Cochrane Stroke Group trials register (last searched
      August 2003), the Chinese Stroke Trials Register (August 2003) and the Chinese
      Acupuncture Trials Register (August 2003). Electronic searches were performed in
      the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2003),
      MEDLINE (1966 to 2003), EMBASE (1980 to 2003), Alternative Medicine Database
      (1985 to 2003), CINAHL (1982 to 2003) and the Chinese Biological Medicine
      Database (1981 to 2003). Reference lists of systematic reviews and identified
      trials were handsearched. SELECTION CRITERIA: Randomised and quasi-randomised
      trials of acupuncture started within 30 days of stroke onset, compared with
      placebo/sham acupuncture or open control in patients with acute ischaemic and/or
      haemorrhagic stroke. Needling into skin was required for acupuncture. DATA
      COLLECTION AND ANALYSIS: Two reviewers selected trials for inclusion, assessed
      trial quality, and extracted the data independently. Authors of trials were
      contacted for missing data. MAIN RESULTS: Fourteen trials involving 1208 patients
      were included. Ten trials included patients with only ischaemic stroke. When
      acupuncture was compared with sham acupuncture or open control, there was a
      borderline significant trend towards fewer patients being dead or dependent (Odds
      ratio (OR) 0.66, 95% confidence interval (CI) 0.43 to 0.99), and significantly
      fewer being dead or needing institutional care (OR 0.58, 95% CI 0.35 to 0.96) in
      the acupuncture group after three months or more. There was also a significant
      difference favouring acupuncture in the mean change of global neurological
      deficit score during the treatment period (standardized mean difference (SMD)
      1.17, 95% CI 0.30 to 2.04). Comparison of acupuncture with sham acupuncture only
      showed a statistically significant difference on death or requiring institutional
      care (OR 0.49, 95% CI 0.25 to 0.96), but not on death or dependency (OR 0.67, 95%
      CI 0.40 to 1.12), or change of global neurological deficit score (SMD 0.01, 95%
      CI -0.55 to 0.57). Severe adverse events with acupuncture (dizziness, intolerable
      pain and infection of acupoints) were rare (6/386, 1.55%). AUTHORS' CONCLUSIONS:
      Acupuncture appeared to be safe but without clear evidence of benefit. The number
      of patients is too small to be certain whether acupuncture is effective for
      treatment of acute ischaemic or haemorrhagic stroke. Larger, methodologically
      sound trials are required.

PMID- 15846658
TI  - In vitro fertilisation for unexplained subfertility.
AB  - BACKGROUND: In vitro fertilisation (IVF) is now a widely accepted treatment for
      unexplained infertility (RCOG 1998). However, with estimated live-birth rates per
      cycle varying between 13% and 28%, its effectiveness has not been rigorously
      evaluated in comparison with other treatments. With increasing awareness of the
      role of expectant management and less invasive procedures such as intrauterine
      insemination, concerns about multiple complications and costs associated with
      IVF, it is extremely important to evaluate the effectiveness of IVF against other
      treatment options in couples with unexplained infertility. OBJECTIVES: The aim of
      this review is to determine, in the context of unexplained infertility, whether
      IVF improves the probability of live-birth compared with (1) expectant
      management, (2) clomiphene citrate (CC), (3) intrauterine insemination (IUI)
      alone, (4) IUI with controlled ovarian stimulation, and (5) gamete intrafallopian
      transfer (GIFT). SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders
      and Subfertility Group Trials Register (searched 23 March 2004), the Cochrane
      Central Register of Controlled Trials (Cochrane Library Issue 3, 2004), MEDLINE
      (1970 to August 2004), EMBASE (1985 to August 2004) and reference lists of
      articles. We also handsearched relevant conference proceedings and contacted
      researchers in the field. SELECTION CRITERIA: Only randomised controlled trials
      were included. Live-birth rate per woman was the primary outcome of interest.
      DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility
      and quality of trials. MAIN RESULTS: Ten randomised controlled trials were
      identified. In two we could not extract data separately for unexplained
      infertility cases, two were non-randomised, one did not report valid rates
      (included in the review but not in the meta-analysis); leaving four trials for
      analysis. One trial compared two different interventions (IVF versus IUI with or
      without ovarian stimulation) and one study compared three interventions (IVF
      versus IUI with ovarian stimulation and GIFT). The numbers of trials assessing
      the effectiveness of IVF with the other treatments were as follows: IVF versus
      expectant management (two), IVF versus IUI (one), IVF versus IUI with ovarian
      stimulation (two) and IVF versus GIFT (three). Live-birth rate per woman was
      reported in three studies and three studies determined clinical pregnancy rate
      per woman. Multiple pregnancy rate was reported in three trials. Two studies
      reported ovarian hyperstimulation syndrome (OHSS) as an outcome measure. There
      were no comparative data for clomiphene citrate and no comparative data on live
      birth rates for GIFT. There was no evidence of a difference in live-birth rates
      between IVF and IUI either without (OR 1.96; 95% CI 0.88 to 4.4) or with (OR
      1.15; 95% CI 0.55 to 2.4) ovarian stimulation. There were significantly higher
      clinical pregnancy rates with IVF in comparison to expectant management (OR 3.24;
      95% CI 1.07 to 9.80). There was no significant difference between IVF and GIFT
      for the one RCT that reported live-birth rates (OR 2.57; 95% CI 0.93 to 7.08).
      However, there was a significant difference in the clinical pregnancy rates
      between IVF and GIFT, with pregnancy rates greater for IVF (OR 2.14; 95% CI 1.08
      to 4.2). There was no evidence of a difference in the multiple pregnancy rates
      between IVF and IUI with ovarian stimulation (OR 0.63; 95% CI 0.27 to 1.5),
      however, IVF had a higher rate than GIFT (OR 6.3; 95% CI 1.7 to 23). Clinical
      heterogeneity was present among the studies included. However, there was no
      evidence of statistical heterogeneity, which allowed the studies to be combined
      for statistical analysis. AUTHORS' CONCLUSIONS: Any effect of IVF relative to
      expectant management, clomiphene citrate, IUI with or without ovarian stimulation
      and GIFT in terms of live-birth rates for couples with unexplained subfertility
      remains unknown. The studies included are limited by their small sample size so
      that even large differences might be hidden. Live-birth rates are seldom
      reported. Periods of follow up are inadequate and unequal. Adverse effects such
      as multiple pregnancies and ovarian hyperstimulation syndrome have also not been
      reported in most studies. Larger trials with adequate power are warranted to
      establish the effectiveness of IVF in these women. Future trials should not only
      report rates per woman/couple but also include adverse effects and costs of the
      treatments as outcomes. Factors that have a major effect on these outcomes such
      as fertility treatment, female partner's age, duration of infertility and
      previous pregnancy history should also be considered.

PMID- 15846659
TI  - Taxane containing regimens for metastatic breast cancer.
AB  - BACKGROUND: It is generally accepted that taxanes are among the most active
      chemotherapy agents in the management of metastatic breast cancer. OBJECTIVES: To
      identify and review the randomised evidence comparing taxane containing
      chemotherapy regimens with regimens not containing a taxane in the management of
      women with metastatic breast cancer. SEARCH STRATEGY: The specialised register
      maintained by the Editorial Base of the Cochrane Breast Cancer Group was searched
      on 2nd May 2003 using the codes for "advanced breast cancer", "chemotherapy".
      Details of the search strategy applied by the Group to create the register, and
      the procedure used to code references, are described in the Group's module on the
      Cochrane Library. SELECTION CRITERIA: Randomised trials comparing taxane
      containing chemotherapy regimens with regimens not containing taxanes in women
      with metastatic breast cancer. DATA COLLECTION AND ANALYSIS: Data were collected
      from published trials. Studies were assessed for eligibility and quality, and
      data were extracted, by two independent reviewers. Hazard ratios were derived for
      time-to-event outcomes where possible, and a fixed effect model was used for meta
      analysis. Response rates were analysed as dichotomous variables. Toxicity and
      quality of life data were extracted where present. MAIN RESULTS: Twenty one
      eligible trials were identified of which 12 have published time-to-event data and
      16 have reported response data. The quality of randomisation was generally not
      described. An estimated 2621 deaths in 3643 randomised women demonstrate a
      statistically significant difference in favour of taxane-containing regimens with
      a HR for overall survival of 0.93 (95% CI=0.86-1.00, p=0.05) and no statistically
      significant heterogeneity. If the analysis is restricted to trials of firstline
      chemotherapy the HR changes to 0.92 and is no longer statistically significant
      (95% CI 0.84-1.02, p=0.11). There was also a significant difference in favour of
      taxanes in relation to time to progression (overall HR 0.92, 95%CI 0.85-0.99,
      p=0.02) and overall response in assessable women (overall OR 1.34, 95%CI 1.18
      1.52, p<0.00001) however there was strong statistical evidence of heterogeneity
      (P<0.00001), probably reflecting the varying efficacy of the comparator regimens
      used in the trials. AUTHORS' CONCLUSIONS: When all trials are considered, taxane
      containing regimens appear to improve overall survival, time to progression and
      overall response in women with metastatic breast cancer. The degree of
      heterogeneity encountered indicates that taxane-containing regimens are more
      effective than some, but not all non-taxane-containing regimens.

PMID- 15846660
TI  - Single agent versus combination chemotherapy for metastatic breast cancer.
AB  - BACKGROUND: It is commonly thought that combining chemotherapy agents for
      treating women with metastatic breast cancer will result in regimens that are
      more active, offer superior tumour response rates with more time before
      progression and improve overall survival. However, it is not known whether giving
      patients more intensive chemotherapy regimens (judged according to some measure
      eg dose, dose intensity, response rate, or toxicity) results in better health
      outcomes. One way to investigate the effect of more versus less-intensive
      chemotherapy is to compare regimens containing a single drug (and hence possibly
      less active treatment) with regimens containing a greater number of drugs (and
      hence possibly more active but more toxic), even when adjustments are made to
      dosages or schedules to account for toxicity. OBJECTIVES: To compare use of
      single chemotherapy agents with regimens containing a combination of agents for
      the treatment of metastatic breast cancer. SEARCH STRATEGY: The Specialised
      Register maintained by the Editorial Base of the Cochrane Breast Cancer Group was
      searched on 2nd May 2003 using the codes for "advanced breast cancer",
      "chemotherapy". Details of the search strategy applied by the group to create the
      register, and the procedure used to code references, are described in the group's
      module on The Cochrane Library. SELECTION CRITERIA: Randomised trials comparing
      single agent chemotherapy with combination therapy in women with metastatic
      breast cancer. DATA COLLECTION AND ANALYSIS: Data were collected from published
      trials. Studies were assessed for eligibility and quality, and data were
      extracted by two independent reviewers. Hazard ratios were derived for time-to
      event outcomes where possible, and a fixed effect model was used for meta
      analysis. Response rates were analysed as dichotomous variables. Toxicity and
      quality of life data were extracted where present. MAIN RESULTS: Thirty seven
      eligible trials were identified of which 28 had published time-to-event data. The
      quality of randomisation was generally not described. Data, based on an estimated
      4220 deaths in 5707 women, show a modest advantage for combination chemotherapy
      regimens compared with single agents with a hazard ratio (HR) for overall
      survival of 0.88 (95% CI=0.83-0.94, P<0.0001) and no evident heterogeneity.
      Results are similar if the analysis is limited to trials in women receiving first
      line chemotherapy. Combination regimens are favourably associated with time to
      progression (overall HR of 0.78 (95% CI=0.73-0.83, P<0.00001) and tumour response
      rates (OR 1.28, CI=1.15-1.42, P<0.00001) although significant heterogeneity was
      observed (P=0.002 and P<0.00001 respectively). This probably reflects the varying
      efficacy of the comparator regimens used in the trials. Women receiving
      combination regimens experienced a higher toxicity level for leukopenia, hair
      loss and nausea and vomiting compared with those receiving a single agent, which
      was statistically significant. AUTHORS' CONCLUSIONS: Compared with single
      chemotherapy agents, combination regimens show a statistically significant
      advantage for tumor response and time to progression in women with metastatic
      breast cancer, a modest improvement in overall survival and significantly worse
      toxicities.

PMID- 15846661
TI  - Psychological treatment of post-traumatic stress disorder (PTSD).
AB  - BACKGROUND: Psychological interventions are widely used in the treatment of post
      traumatic stress disorder (PTSD). OBJECTIVES: To perform a systematic review of
      randomised controlled trials of all psychological treatments except eye movement
      desensitisation and reprocessing following the guidelines of the Cochrane
      Collaboration. SEARCH STRATEGY: Systematic searches of computerised databases,
      hand search of the Journal of Traumatic Stress, searches of reference lists,
      known websites and discussion fora, and personal communication with key workers.
      SELECTION CRITERIA: Types of studies - Any randomised controlled trial of a
      psychological treatment. Types of participants - Adults suffering from traumatic
      stress symptoms for three months or more. Types of interventions - Trauma-focused
      cognitive behavioural therapy/exposure therapy (TFCBT); stress management (SM);
      other therapies (supportive therapy, non-directive counselling, psychodynamic
      therapy and hypnotherapy); group cognitive behavioural therapy (group CBT). Types
      of outcomes - Severity of clinician rated traumatic stress symptoms. Secondary
      measures included self-reported traumatic stress symptoms, depressive symptoms,
      anxiety symptoms, adverse effects and dropouts. DATA COLLECTION AND ANALYSIS:
      Data was entered using the Review Management software. Quality assessments were
      performed. The data were analysed for summary effects using the RevMan 4.2
      programme. MAIN RESULTS: Twenty-nine studies were included in the review. With
      regards to reduction of clinician assessed PTSD symptoms TFCBT did significantly
      better than waitlist/usual care (standardised mean difference (SMD) = -1.36; 95%
      CI, -1.88 to -0.84; 13 studies; n = 609). There was no significant difference
      between TFCBT and SM (SMD = -0.27; 95% CI, -0.71 to 0.16; 6 studies; n = 239).
      TFCBT did significantly better than other therapies (SMD = -0.81; 95% CI, -1.19
      to -0.42; 3 studies; n = 120). Stress management did significantly better than
      waitlist/usual care (SMD = -1.14; 95% CI, -1.62 to -0.67; 3 studies; n = 86) and
      than other therapies (SMD = -1.22; 95% CI, -2.09 to -0.35; 1 study; n = 25).
      There was no significant difference between other therapies and waitlist/usual
      care control (SMD = -0.43; 95% CI, -0.90 to 0.04; 2 studies; n = 72). Group TFCBT
      was significantly better than waitlist/usual care (SMD = -0.72; 95% CI, -1.14 to 
      0.31). AUTHORS' CONCLUSIONS: There was evidence that individual TFCBT, stress
      management and group TFCBT are effective in the treatment of PTSD. Other non
      trauma focused psychological treatments did not reduce PTSD symptoms as
      significantly. There was some evidence that individual TFCBT is superior to
      stress management in the treatment of PTSD at between 2 and 5 months following
      treatment, and also that TFCBT was also more effective than other therapies.
      There was insufficient evidence to determine whether psychological treatment is
      harmful. There was some evidence of greater drop-out in active treatment groups.

PMID- 15846662
TI  - Heroin maintenance for chronic heroin dependents.
AB  - BACKGROUND: Many medications have been used for stabilizing heroin users:
      Methadone, Buprenorphine and LAAM. The present review focus on the prescription
      of heroin to heroin dependents. OBJECTIVES: To assess the efficacy and
      acceptability of heroin maintenance versus methadone or other substitution
      treatments for opioid dependence, in retaining patients in treatment; reducing
      the use of illicit substances and improving health and social functioning. SEARCH
      STRATEGY: The Cochrane Central Register of Trials (CENTRAL) issue 1, 2005;
      MEDLINE 1966-2005, EMBASE 1980-2005 and CINAHL till 2005 (on OVID) were searched.
      There was no language or publication year restrictions. Many researchers were
      contacted for information. SELECTION CRITERIA: Randomised controlled trials of
      heroin (alone or combined with methadone) maintenance treatment compared with any
      other pharmacological treatments for heroin dependents. DATA COLLECTION AND
      ANALYSIS: The trials were independently assessed for inclusion and methodological
      quality by the reviewers. Data were extracted independently and double checked.
      Studies were not pooled together because of heterogeneity. MAIN RESULTS: 2400
      references were obtained and 20 studies were eligible, 4 met the inclusion
      criteria for a total of 577 patients. The studies could not be analysed
      cumulatively because of heterogeneity of interventions and outcomes. Retention in
      treatment: no groups difference was found in two studies; one study (N=96) found
      RR=2.82 (95% CI 1.70-4.68) favouring heroin; one study (N=235) found RR 0.79
      (95%CI 0.68-0.90) favouring methadone. Relapse to illegal heroin use (self-
      reported): in one study people using heroin in treatment was 64% (heroin
      group)and 59% (methadone group); in the other study the RR of heroin use was 0.33
      (95%CI 0.15-0.72) favouring heroin. Criminal offence: one study showed the
      potential of heroin prescription in reducing the risk of being charged RR 0.32
      (95% CI 0.14-0.78). Social functioning: two studies did not show statistical
      difference between intervention groups, and two studies considered criminal
      offence and social functioning as part of a multidomain outcome measure showing
      improvements among those treated with heroin plus methadone over those on
      methadone only. AUTHORS' CONCLUSIONS: No definitive conclusions about the overall
      effectiveness of heroin prescription is possible. Results favouring heroin
      treatment come from studies conducted in countries where easily accessible
      Methadone Maintenance Treatment at effective dosages is available. In those
      studies heroin prescription was addressed to patients who had failed previous
      methadone treatments. The present review contains information about ongoing
      trials which results will be integrated as soon as available.

PMID- 15846663
TI  - Group based training for self-management strategies in people with type 2
      diabetes mellitus.
AB  - BACKGROUND: It has been recognised that adoption of self-management skills by the
      person with diabetes is necessary in order to manage their diabetes. However, the
      most effective method for delivering education and teaching self-management
      skills is unclear. OBJECTIVES: To assess the effects of group-based, patient
      centred training on clinical, lifestyle and psychosocial outcomes in people with
      type 2 diabetes. SEARCH STRATEGY: Studies were obtained from computerised
      searches of multiple electronic bibliographic databases, supplemented by hand
      searches of reference lists of articles, conference proceedings and consultation
      with experts in the field. Date of last search was February 2003. SELECTION
      CRITERIA: Randomised controlled and controlled clinical trials which evaluated
      group-based education programmes for adults with type 2 diabetes compared with
      routine treatment, waiting list control or no intervention. Studies were only
      included if the length of follow-up was six months or more and the intervention
      was at least one session with the minimum of six participants. DATA COLLECTION
      AND ANALYSIS: Two reviewers independently extracted data and assessed study
      quality. A meta-analysis was performed if there were enough homogeneous studies
      reporting an outcome at either four to six months, 12-14 months, or two years,
      otherwise the studies were summarised in a descriptive manner. MAIN RESULTS:
      Fourteen publications describing 11 studies were included involving 1532
      participants. The results of the meta-analyses in favour of group-based diabetes
      education programmes were reduced glycated haemoglobin at four to six months
      (1.4%; 95% confidence interval (CI) 0.8 to 1.9; P < 0.00001), at 12-14 months
      (0.8%; 95% CI 0.7 to 1.0; P < 0.00001) and two years (1.0%; 95% CI 0.5 to 1.4; P
      < 0.00001); reduced fasting blood glucose levels at 12 months (1.2 mmol/L; 95% CI
      0.7 to 1.6; P < 0.00001); reduced body weight at 12-14 months (1.6 Kg; 95% CI 0.3
      to 3.0; P = 0.02); improved diabetes knowledge at 12-14 months (SMD 1.0; 95% CI
      0.7 to 1.2; P < 0.00001) and reduced systolic blood pressure at four to six
      months (5 mmHg: 95% CI 1 to 10; P = 0.01). There was also a reduced need for
      diabetes medication (odds ratio 11.8, 95% CI 5.2 to 26.9; P < 0.00001; RD = 0.2;
      NNT = 5). Therefore, for every five patients attending a group-based education
      programme we could expect one patient to reduce diabetes medication. AUTHORS'
      CONCLUSIONS: Group-based training for self-management strategies in people with
      type 2 diabetes is effective by improving fasting blood glucose levels, glycated
      haemoglobin and diabetes knowledge and reducing systolic blood pressure levels,
      body weight and the requirement for diabetes medication.

PMID- 15846664
TI  - Antithyroid drug regimen for treating Graves' hyperthyroidism.
AB  - BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism.
      There are wide variations in the dose, regimen or duration of treatment used by
      health professionals. OBJECTIVES: To assess the effects of dose, regimen and
      duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials
      and reference lists. We contacted investigators and hand searched conference
      abstracts. Most recent search: July 2004. SELECTION CRITERIA: Randomised and
      quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism
      were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded
      and awaiting assessment categories was made by consensus. Two reviewers
      independently extracted data and assessed trial quality. Pooling of data for
      primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS:
      Twenty-three randomised trials involving 3115 participants were included. Overall
      the quality of trials as reported was poor; specifically in terms of allocation
      concealment, assessor blinding and loss to follow-up. Four trials examined the
      effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one
      trial using the Titration regimen, longer duration therapy (18 months) had
      significantly fewer relapses (37% versus 58%) than six month therapy (Odds ratio
      (OR) 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised
      trial using the Block-Replace regimen, there was no significant difference
      between the six and 12 month (relapses rates 41% versus 35%) arms of the study.
      Extending the duration of therapy to over 18 months was not associated with
      improved relapse rates (Peto OR 0.75, 95% CI 0.39 to 1.43). Twelve trials
      examined the effect of Block-Replace versus Titration regimen. The relapse rates
      were similar in both groups at 51% in the Block-Replace group and 54% in the
      Titration group (Peto OR 0.86, 95% CI 0.68 to 1.08). Participants reporting
      rashes (10% versus 5%) and withdrawing due to side effects (16% versus 9%) were
      significantly higher in the Block-Replace group compared to the Titration group
      respectively. Three studies considered the addition of thyroxine with continued
      low dose antithyroid therapy after initial therapy with antithyroid drugs. There
      was significant heterogeneity between the studies and the difference between the
      two groups were not significant (Odds ratio 0.58, 95% CI 0.05 to 6.21). Four
      studies considered the addition of thyroxine alone after initial therapy with
      antithyroid drugs. There was no significant difference in the relapse rates
      between the groups after 12 months follow-up with relapse rates being 31%
      (88/282) with thyroxine and 29% (82/284) with placebo (Peto OR 1.15, 95% CI 0.79
      to 1.67). AUTHORS' CONCLUSIONS: The evidence (based on four studies) suggests
      that the optimal duration of antithyroid drug therapy for the Titration regimen
      is 12 to 18 months. The six month Block-Replace regimen was found to be as
      effective as the 12 month treatment in one quasi-randomised study. The Titration
      (low dose) regimen had fewer adverse effects than the Block-Replace (high dose)
      regimen and was no less effective in trials (based on 12 trials) of equal
      duration. Continued thyroxine treatment following initial antithyroid therapy
      does not appear to provide any benefit in terms of recurrence of hyperthyroidism.
      The incidence of hypothyroidism was not reported and there were no deaths
      reported in the study populations.

PMID- 15846665
TI  - Calcium channel blockers for preventing acute tubular necrosis in kidney
      transplant recipients.
AB  - BACKGROUND: The incidence of delayed graft function in cadaveric grafts has
      increased over the last few years due in part to the large demand for cadaveric
      kidneys necessitating the use of kidneys from marginal donors. Calcium channel
      blockers have the potential to reduce the incidence of post-transplant acute
      tubular necrosis (ATN) if given in the peri-operative period. However, there is
      controversy surrounding their use in this situation with no consensus as to their
      efficacy. OBJECTIVES: To evaluate the benefits and harms of using calcium channel
      blockers in the peri-transplant period in patients at risk of ATN following
      cadaveric kidney transplantation. SEARCH STRATEGY: We searched the Cochrane Renal
      Group's specialised register, the Cochrane Central Register of Controlled Trials
      (CENTRAL, in The Cochrane Library) MEDLINE (from 1966) and EMBASE (from 1980).
      The Trials Search Coordinator was contacted to develop the search strategy. Date
      of last database and register search: January 2005 SELECTION CRITERIA: Randomised
      controlled trials comparing calcium channel blockers given in the peri-transplant
      period with controls were included. Quasi-randomised trials were excluded. DATA
      COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by
      two reviewers, with differences resolved by discussion. Dichotomous outcomes are
      reported as relative risk (RR) and measurements on continuous scales are reported
      as weighted mean differences (WMD) with 95% confidence intervals (CI). MAIN
      RESULTS: Ten trials were suitable for inclusion. Treatment with calcium channel
      blockers in the peri-transplant period was associated with a significant decrease
      in the incidence of post transplant ATN (RR 0.57, 95%CI 0.40 to 0.82) and delayed
      graft function (RR 0.51, 95% CI 0.36 to 0.72). There was no difference between
      control and treatment groups in graft loss, mortality, requirement for
      haemodialysis. There was insufficient information to comment on adverse events.
      AUTHORS' CONCLUSIONS: These results suggest that calcium channel blockers given
      in the peri-operative period may reduce the incidence of ATN post
      transplantation. The result should be treated with caution due to the
      heterogeneity of the trials which made comparison of studies and pooling of data
      difficult.

PMID- 15846666
TI  - Clotting factor concentrates given to prevent bleeding and bleeding-related
      complications in people with hemophilia A or B.
AB  - BACKGROUND: People with severe hemophilia A or B, X-linked bleeding disorders due
      to decreased blood levels of coagulants, suffer recurrent bleeding into joints
      and soft tissues. Before clotting factor concentrates were available, most people
      with severe hemophilia developed crippling musculoskeletal deformities. Clotting
      factor concentrate prophylaxis aims to preserve joint function by converting
      severe hemophilia (factor VIII or IX less than 1%) into a clinically milder form
      of the disease. Prophylaxis has long been used in Sweden, but not universally
      adopted because of medical, psychosocial, and cost controversies. Use of clotting
      factor concentrates is the single largest predictor of cost in treating
      hemophilia. OBJECTIVES: To determine the effectiveness of clotting factor
      concentrate prophylaxis in the management of people with hemophilia A or B.
      SEARCH STRATEGY: We searched the Cystic Fibrosis and Genetic Disorders Group's
      Trials Register comprising references from comprehensive electronic database
      searches and handsearches of journals and abstract books. Reference lists of
      relevant articles were reviewed. Most recent search: January 2002. SELECTION
      CRITERIA: Randomized controlled trials (RCTs) evaluating people with severe
      hemophilia A or B, receiving prophylactic clotting factor concentrates. DATA
      COLLECTION AND ANALYSIS: Two reviewers independently reviewed studies for
      eligibility, assessed methodological quality and extracted data. MAIN RESULTS:
      Twenty-nine studies were identified, of which four (including 37 participants)
      were eligible for inclusion. Three studies evaluated hemophilia A; one showed a
      decrease in frequency of joint bleeds with prophylaxis compared to placebo (non
      physiological dose), with a rate difference (RD) -10.80 (95% confidence interval
      (CI) -16.33 to -5.27) bleeds per year. The remaining two studies evaluating
      hemophilia A compared two prophylaxis regimens, one study showed no difference in
      joint bleed frequency, RD -5.04 (95%CI -17.02 to 6.94) bleeds per year and
      another failed to demonstrate an advantage of factor VIII dosing based on
      individual pharmacokinetic data over the standard prophylaxis regimen with RD 
      0.14 (95% CI -1.34 to 1.05) bleeds per year. The fourth study evaluated
      hemophilia B and showed fewer joint bleeds with weekly (15 IU/kg) versus bi
      weekly (7.5 IU/kg) prophylaxis, RD -3.30 (95% CI -5.50 to - 1.10) bleeds per
      year. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether
      prophylactic clotting factor concentrates decrease bleeding and bleeding-related
      complications in hemophilia A or B, compared to placebo, on-demand treatment, or
      prophylaxis based on pharmacokinetic data from individuals. Well-designed RCTs
      are needed to assess the effectiveness of prophylactic clotting factor
      concentrates. Two clinical trials are ongoing.

PMID- 15846667
TI  - Workplace interventions for smoking cessation.
AB  - BACKGROUND: The workplace has potential as a setting through which large groups
      of people can be reached to encourage smoking cessation. OBJECTIVES: To
      categorize workplace interventions for smoking cessation tested in controlled
      studies and to determine the extent to which they help workers to stop smoking or
      to reduce tobacco consumption. SEARCH STRATEGY: We searched the Cochrane Tobacco
      Addiction Group Specialized Register in October 2004, MEDLINE (1966 - October
      2004), EMBASE (1985 - October 2004) and PsycINFO (to October 2004). We searched
      abstracts from international conferences on tobacco and we checked the
      bibliographies of identified studies and reviews for additional references.
      SELECTION CRITERIA: We categorized interventions into two groups: a)
      Interventions aimed at the individual to promote smoking cessation and b)
      interventions aimed at the workplace as a whole. We applied different inclusion
      criteria for the different types of study. For interventions aimed at helping
      individuals to stop smoking, we included only randomized controlled trials
      allocating individuals, workplaces or companies to intervention or control
      conditions. For studies of smoking restrictions and bans in the workplace, we
      also included controlled trials with baseline and post-intervention outcomes and
      interrupted times series studies. DATA COLLECTION AND ANALYSIS: Information
      relating to the characteristics and content of all kinds of interventions,
      participants, outcomes and methods of the study was abstracted by one author and
      checked by two others. Because of heterogeneity in the design and content of the
      included studies, we did not attempt formal meta-analysis, and evaluated the
      studies using qualitative narrative synthesis. MAIN RESULTS: Workplace
      interventions aimed at helping individuals to stop smoking included ten studies
      of group therapy, seven studies of individual counselling, nine studies of self
      help materials and five studies of nicotine replacement therapy. The results were
      consistent with those found in other settings. Group programmes, individual
      counselling and nicotine replacement therapy increased cessation rates in
      comparison to no treatment or minimal intervention controls. Self-help materials
      were less effective.Workplace interventions aimed at the workforce as a whole
      included 14 studies of tobacco bans, two studies of social support, four studies
      of environmental support, five studies of incentives, and eight studies of
      comprehensive (multi-component) programmes. Tobacco bans decreased cigarette
      consumption during the working day but their effect on total consumption was less
      certain. We failed to detect an increase in quit rates from adding social and
      environmental support to these programmes. There was a lack of evidence that
      comprehensive programmes reduced the prevalence of smoking. Competitions and
      incentives increased attempts to stop smoking, though there was less evidence
      that they increased the rate of actual quitting. AUTHORS' CONCLUSIONS: We found:
      1. Strong evidence that interventions directed towards individual smokers
      increase the likelihood of quitting smoking. These include advice from a health
      professional, individual and group counselling and pharmacological treatment to
      overcome nicotine addiction. Self-help interventions are less effective. All
      these interventions are effective whether offered in the workplace or elsewhere.
      Although people taking up these interventions are more likely to stop, the
      absolute numbers who quit are low. 2. Limited evidence that participation in
      programmes can be increased by competitions and incentives organized by the
      employer. 3. Consistent evidence that workplace tobacco policies and bans can
      decrease cigarette consumption during the working day by smokers and exposure of
      non-smoking employees to environmental tobacco smoke at work, but conflicting
      evidence about whether they decrease prevalence of smoking or overall consumption
      of tobacco by smokers. 4. A lack of evidence that comprehensive approaches reduce
      the prevalence of smoking, despite the strong theoretical rationale for their
      use. 5. A lack of evidence about the cost-effectiveness of workplace programmes.

PMID- 15846668
TI  - Bulking agents, antispasmodic and antidepressant medication for the treatment of
      irritable bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a common health problem, often
      presenting in primary care as well as in internal medicine and gastroenterology
      outpatient clinics. Therapeutic options are dominated by drug therapies but there
      is uncertainty about their effectiveness. OBJECTIVES: The primary objective of
      this review was to evaluate the efficacy of bulking agents, antispasmodic and
      antidepressant medication for the treatment of IBS. SEARCH STRATEGY: A computer
      assisted search of MEDLINE, EMBASE, PsychInfo and the Cochrane Library was
      performed for the years 1966-2001; local and national databases were searched in
      10 European countries. SELECTION CRITERIA: Randomised trials comparing bulking
      agents, antispasmodic or antidepressant medications with a placebo, in IBS
      patients over 12 years of age. Only studies published as a full paper were
      included. No language criterion was applied. DATA COLLECTION AND ANALYSIS: The
      search identified 687 studies, 66 of which fulfilled all eligibility criteria.
      After removal of cross-over studies that did not report separately on the first
      phase, data from 40 studies remained for analysis. Relative risk (RR), risk
      difference (RD) and standardized mean difference (SMD) along with 95% confidence
      intervals were calculated for all subgroups. The number needed to treat (NNT) was
      also calculated where appropriate. MAIN RESULTS: Forty-one study reports from 40
      studies, comprising 78 comparisons, were analysed. These included 11 reports on
      bulking agents, 6 on antidepressants, and 24 on spasmolytics.BULKING AGENTS:
      Three studies comprising 159 patients reported a dichotomous outcome for relief
      of abdominal pain. The pooled RR using a random effects model was 1.22 (95% CI
      0.86 - 1.73). Three studies comprising 128 patients reported a continuous outcome
      for relief of abdominal pain. Using the random effects model, the SMD was 0.68
      (95% CI -0.86 - 2.33). Nine studies comprising 482 patients reported a
      dichotomous outcome for global assessment of improvement. The pooled RR was 1.09
      (95% CI 0.78 - 1.50). Five studies comprising 253 patients reported a dichotomous
      outcome for improvement of symptom score. The pooled RR using a random effects
      model was 0.93 (95% CI 0.56 - 1.54). Two studies comprising 70 patients reported
      a continuous outcome for improvement of symptom score; the SMD using a fixed
      effects model was -0.44 (95% CI -1.20 - 0.31). SPASMOLYTIC AGENTS: Eleven studies
      comprising 1260 patients reported a dichotomous outcome for relief of abdominal
      pain. The pooled RR using a random effects model was 1.34 (95% CI 1.13 - 1.59;
      RD=0.17, 95% CI 0.06 -0.28; NNT=6, 95% CI 4 - 15). Seven studies comprising 467
      patients reported a continuous outcome for relief of abdominal pain. Using a
      fixed effects model the pooled SMD was -0.65 (95% CI -0.94 to -0.35). Sixteen
      studies comprising 1236 patients reported a dichotomous outcome for global
      assessment of improvement. The pooled RR using a random effects model was 1.42
      (95% CI 1.17 - 1.72; RD=0.20, 95% CI 0.09 -0.30; NNT=5, 95% CI 3 - 11). One study
      comprising 34 patients reported a dichotomous variable for improvement of symptom
      score. The RR was 1.33 (95% CI 0.96 - 1.85). Three studies reported a continuous
      outcome for improvement of symptom score; two studies comprising 66 patients
      could be pooled. Using a fixed effects model, the SMD was -0.37 (95% CI -0.85 -
      0.12). ANTIDEPRESSANTS: Two studies comprising 81 patients reported a dichotomous
      outcome for relief of abdominal pain. Using the random effects model, the pooled
      RR was 0.83 (95% CI 0.33 - 2.12). Two studies comprising 101 patients reported a
      continuous outcome for relief of abdominal pain. The SMD using a random effects
      model was -0.53 (95% CI -2.29 - 1.23). Four studies comprising 241 patients
      reported a dichotomous variable for global assessment of improvement. The pooled
      RR was 1.16 (95% CI 0.78 - 1.73). AUTHORS' CONCLUSIONS: The evidence for efficacy
      of drug therapies for IBS is weak. Although there is evidence of benefit for
      antispasmodic drugs for abdominal pain and global assessment of symptoms; it is
      unclear whether anti-spasmodic subgroups are individually effective. There is no
      clear evidence of benefit for antidepressants or bulking agents. The physician
      should be aware that global assessment is a construct containing various
      dimensions. For each individual, these will have a different weighting and
      treatment should be aimed at the most debilitating symptom. Stool problems are by
      definition part of the IBS symptom complex. Bulking agents may improve
      constipation and can be used empirically, but should be evaluated at an early
      stage for individual benefit. Future research should pay attention to study
      methodology and the use of valid outcome measures.

PMID- 15846669
TI  - Bed rest during pregnancy for preventing miscarriage.
AB  - BACKGROUND: Miscarriage is pregnancy loss before 23 weeks of gestational age and
      it happens in 10% to 15% of pregnancies depending on maternal age and parity. It
      is associated with chromosomal defects in about a half or two thirds of cases.
      Many interventions have been used to prevent miscarriage but bed rest is probably
      the most commonly prescribed especially in cases of threatened miscarriage and
      history of previous miscarriage. Since the etiology of miscarriage in most of the
      cases is not related to an excess of activity, it is unlikely that bed rest could
      be an effective strategy to reduce spontaneous miscarriage. OBJECTIVES: To
      evaluate the effect of prescription of bed rest during pregnancy to prevent
      miscarriage in women at high risk of miscarriage. SEARCH STRATEGY: We searched
      the Cochrane Pregnancy and Childbirth Group trials register (July 2004). In
      addition, we searched The Cochrane Central Register of Controlled Trials (The
      Cochrane Library), MEDLINE, POPLINE, LILACS and EMBASE. SELECTION CRITERIA: We
      included all published, unpublished and ongoing randomized trials with reported
      data which compare clinical outcomes in pregnant women who were prescribed bed
      rest in hospital or at home for preventing miscarriage compared with alternative
      care or no intervention. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed the methodological quality of included trials using the methods
      described in the Cochrane Reviewers' Handbook. Studies were included irrespective
      of their methodological quality. MAIN RESULTS: Only two studies including 84
      women were identified. There was no statistically significant difference in the
      risk of miscarriage in the bed rest group versus the no bed rest group (placebo
      or other treatment) (relative risk (RR) 1.54, 95% confidence interval (CI) 0.92
      to 2.58). Neither bed rest in hospital nor bed rest at home showed a significant
      difference in the prevention of miscarriage. There was a higher risk of
      miscarriage in those women in the bed rest group than in those in the human
      chorionic gonadotrophin therapy group with no bed rest (RR 2.50, 95% CI 1.22 to
      5.11). It seems that the small number of participants included in these studies
      is a main factor to make this analysis inconclusive. AUTHORS' CONCLUSIONS: There
      is insufficient evidence of high quality that supports a policy of bed rest in
      order to prevent miscarriage in women with confirmed fetal viability and vaginal
      bleeding in first half of pregnancy.

PMID- 15846670
TI  - Non-steroidal anti-inflammatory drugs and perioperative bleeding in paediatric
      tonsillectomy.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for pain
      relief following tonsillectomy in children. However, as they inhibit platelet
      aggregation and prolong bleeding time, they could cause increased perioperative
      bleeding. The overall risk remains unclear. OBJECTIVES: The primary objective of
      this review was to assess the effects of NSAIDs on bleeding for paediatric
      tonsillectomy. There is good evidence (Kokki 2003; Romsing 1997) to show that
      NSAIDs are effective analgesics in children. It was not the remit of our review
      to question this, but rather to assess the risk of bleeding when NSAIDs are used
      for pain relief following paediatric tonsillectomy. SEARCH STRATEGY: We searched
      the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library, Issue 3, 2004); MEDLINE (inception until August 2004); EMBASE (from
      inception until August 2004), Current Problems (produced by the UK Medicines
      Control Agency); MedWatch (produced by the US Food and Drug Administration) and
      the Australian Adverse Drug Reactions Bulletin in December 2001. The Cochrane
      Anaesthesia Review Group's handsearch co-ordinator performed handsearching as
      required. We also contacted manufacturers and researchers in the field. SELECTION
      CRITERIA: We included randomized controlled trials assessing NSAIDs in children
      up to and including 16 years of age, undergoing elective tonsillectomy or
      adenotonsillectomy. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trial quality and extracted the data. We contacted study authors where
      necessary for additional information. We also collected information on adverse
      effects from the trials. MAIN RESULTS: We included 13 trials involving 955
      children. All included trials compared NSAIDs with other analgesics or placebo
      and looked at bleeding requiring surgical intervention. NSAIDs did not
      significantly alter number of perioperative bleeding events requiring surgical
      intervention; Peto odds ratio 1.46 (95% confidence interval 0.49 to 4.40). Seven
      trials involving 471 children looked at bleeding not requiring surgical
      intervention. NSAIDs did not significantly alter number of perioperative bleeding
      events not requiring surgical intervention; Peto odds ratio 1.23 (95% confidence
      interval 0.44 to 3.43). Ten trials involving 837 children looked at post
      operative nausea and vomiting. There was less nausea and vomiting when NSAIDs
      were used as part of the analgesic regime, compared to when NSAIDs were not used;
      Odds ratio 0.40 (95% confidence interval 0.23 to 0.72). AUTHORS' CONCLUSIONS:
      NSAIDs did not cause any increase in bleeding requiring a return to theatre.
      There was significantly less nausea and vomiting when NSAIDs were used compared
      to alternative analgesics.

PMID- 15846671
TI  - Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases.
AB  - BACKGROUND: Alcohol and hepatotoxic viruses cause the majority of liver diseases.
      Randomised clinical trials have assessed whether extracts of milk thistle,
      Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or
      hepatitis B or C virus liver diseases. OBJECTIVES: To assess the beneficial and
      harmful effects of milk thistle or milk thistle constituents versus placebo or no
      intervention in patients with alcoholic liver disease and/or viral liver diseases
      (hepatitis B and hepatitis C). SEARCH STRATEGY: The Cochrane Hepato-Biliary Group
      Controlled Trials Register, The Cochrane Central Register of Controlled Trials,
      MEDLINE, EMBASE, and full text searches were combined (December 2003).
      Manufacturers and researchers in the field were contacted. SELECTION CRITERIA:
      Only randomised clinical trials in patients with alcoholic and/or hepatitis B or
      C virus liver diseases (acute and chronic) were included. Interventions
      encompassed milk thistle at any dose or duration versus placebo or no
      intervention. The trials could be double blind, single blind, or unblinded. The
      trials could be unpublished or published and no language limitations were
      applied. DATA COLLECTION AND ANALYSIS: The primary outcome measure was mortality.
      Binary outcomes are reported as relative risks (RR) with 95% confidence interval
      (CI). Subgroup analyses were performed with regard to methodological quality.
      MAIN RESULTS: Thirteen randomised clinical trials assessed milk thistle in 915
      patients with alcoholic and/or hepatitis B or C virus liver diseases. The
      methodological quality was low: only 23% of the trials reported adequate
      allocation concealment and only 46% were considered adequately double-blinded.
      Milk thistle versus placebo or no intervention had no significant effect on
      mortality (RR 0.78, 95% CI 0.53 to 1.15), complications of liver disease (RR
      0.95, 95% CI 0.83 to 1.09), or liver histology. Liver-related mortality was
      significantly reduced by milk thistle in all trials (RR 0.50, 95% CI 0.29 to
      0.88), but not in high-quality trials (RR 0.57, 95% CI 0.28 to 1.19). Milk
      thistle was not associated with a significantly increased risk of adverse events
      (RR 0.83, 95% CI 0.46 to 1.50). AUTHORS' CONCLUSIONS: Our results question the
      beneficial effects of milk thistle for patients with alcoholic and/or hepatitis B
      or C virus liver diseases and highlight the lack of high-quality evidence to
      support this intervention. Adequately conducted and reported randomised clinical
      trials on milk thistle versus placebo are needed.

PMID- 15846672
TI  - Interventions for improving adherence to treatment recommendations in people with
      type 2 diabetes mellitus.
AB  - BACKGROUND: Research suggests adherence to treatment recommendations is low. In
      type 2 diabetes, which is a chronic condition slowly leading to serious vascular,
      nephrologic, neurologic and ophthalmological complications, it can be assumed
      that enhancing adherence to treatment recommendations may lead to a reduction of
      complications. Treatment regimens in type 2 diabetes are complicated,
      encompassing life-style adaptations and medication intake. OBJECTIVES: To assess
      the effects of interventions for improving adherence to treatment recommendations
      in people with type 2 diabetes mellitus. SEARCH STRATEGY: Studies were obtained
      from searches of multiple electronic bibliographic databases supplemented with
      hand searches of references. Date of last search: November 2002. SELECTION
      CRITERIA: Randomised controlled and controlled clinical trials, before-after
      studies and epidemiological studies, assessing changes in adherence to treatment
      recommendations, as defined in the objectives section, were included. DATA
      COLLECTION AND ANALYSIS: Two teams of reviewers independently assessed the trials
      identified for inclusion. Three teams of two reviewers assessed trial quality and
      extracted data. The analysis for the narrative part was performed by one reviewer
      (EV), the meta-analysis by two reviewers (EV, JW). MAIN RESULTS: Twentyone
      studies assessing interventions aiming at improving adherence to treatment
      recommendations, not to diet or exercise recommendations, in people living with
      type 2 diabetes in primary care, outpatient settings, community and hospital
      settings, were included. Outcomes evaluated in these studies were heterogeneous,
      there was a variety of adherence measurement instruments. Nurse led
      interventions, home aids, diabetes education, pharmacy led interventions,
      adaptation of dosing and frequency of medication taking showed a small effect on
      a variety of outcomes including HbA1c. No data on mortality and morbidity, nor on
      quality of life could be found. AUTHORS' CONCLUSIONS: Current efforts to improve
      or to facilitate adherence of people with type 2 diabetes to treatment
      recommendations do not show significant effects nor harms. The question whether
      any intervention enhances adherence to treatment recommendations in type 2
      diabetes effectively, thus still remains unanswered.

PMID- 15846673
TI  - Alpha-glucosidase inhibitors for type 2 diabetes mellitus.
AB  - BACKGROUND: Alpha-glucosidase inhibitors such as acarbose or miglitol, have the
      potential to improve glycemic control in type 2 diabetes mellitus. The true value
      of these agents, especially in relation to diabetes related mortality and
      morbidity, has never been investigated in a systematic literature review and meta
      analysis. OBJECTIVES: To assess the effects of alpha-glucosidase inhibitors s in
      patients with type 2 diabetes mellitus. SEARCH STRATEGY: We searched The Cochrane
      Library, MEDLINE, EMBASE, Current Contents, LILACS, databases of ongoing trials,
      reference lists of reviews on the topic of alpha-glucosidase inhibitors and we
      contacted experts and manufacturers for additional trials. Date of most recent
      search: December 2003 (Current Contents) and April 2003 (other databases).
      SELECTION CRITERIA: Randomised controlled trials of at least 12 weeks duration
      comparing alpha-glucosidase inhibitor monotherapy in patients with type 2
      diabetes with any other intervention and that included at least one of the
      following outcomes: mortality, morbidity, quality of life, glycemic control,
      lipids, insulin levels, body weight, adverse events. DATA COLLECTION AND
      ANALYSIS: Two reviewers read all abstracts, assessed quality and extracted data
      independently. Discrepancies were resolved by consensus or by the judgement of a
      third reviewer. A statistician checked all extracted data entrance in the
      database. We attempted to contact all authors for data clarification. MAIN
      RESULTS: We included 41 trials (8130 participants), 30 investigated acarbose,
      seven miglitol, one trial voglibose and three trials compared different alpha
      glucosidase inhibitors. Study duration was 24 weeks in most cases and only two
      studies lasted amply longer than one year. We found only few data on mortality,
      morbidity and quality of life. Acarbose had a clear effect on glycemic control
      compared to placebo: glycated haemoglobin -0.8% (95% confidence interval -0.9 to 
      0.7), fasting blood glucose -1.1 mmol/L (95% confidence interval -1.4 to -0.9),
      post-load blood glucose -2.3 mmol/L (95% confidence interval -2.7 to -1.9). The
      effect on glycated haemoglobin by acarbose was not dose-dependent. We found a
      decreasing effect on post-load insulin and no clinically relevant effects on
      lipids or body weight. Adverse effects were mostly of gastro-intestinal origin
      and dose dependent. Compared to sulphonylurea, acarbose decreased fasting and
      post-load insulin levels by -24.8 pmol/L (95% confidence interval -43.3 to -6.3)
      and -133.2 pmol/L (95% confidence interval -184.5 to -81.8) respectively and
      acarbose caused more adverse effects. AUTHORS' CONCLUSIONS: It remains unclear
      whether alpha-glucosidase inhibitors influence mortality or morbidity in patients
      with type 2 diabetes. Conversely, they have a significant effect on glycemic
      control and insulin levels, but no statistically significant effect on lipids and
      body weight. These effects are less sure when alpha-glucosidase inhibitors are
      used for a longer duration. Acarbose dosages higher than 50 mg TID offer no
      additional effect on glycated hemoglobin but more adverse effects instead.
      Compared to sulphonylurea, alpha-glucosidase inhibitors lower fasting and post
      load insulin levels and have an inferior profile regarding glycemic control and
      adverse effects.

PMID- 15846674
TI  - Positioning for acute respiratory distress in hospitalised infants and children.
AB  - BACKGROUND: Because of the association between prone positioning and sudden
      infant death syndrome SIDS) it is recommended that young infants be placed on
      their backs (supine). However, the supine position might not be the most
      appropriate position for infants and children hospitalised with acute respiratory
      distress. Positioning patients has been proposed as a non-invasive way of
      increasing oxygenation in adult patients with acute respiratory distress. But,
      because of substantial differences in respiratory mechanics between adults and
      children and the risk of SIDS in young infants, a specific review of positioning
      for infants and young children with acute respiratory distress is warranted.
      OBJECTIVES: To compare the effects of different body positions in hospitalised
      infants and children with acute respiratory distress. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library Issue 3, 2004); MEDLINE (January 1966 to October Week 3, 2004);
      EMBASE (1980 to week 24, 2004); and CINAHL (1982 to October Week 3, 2004).
      SELECTION CRITERIA: All randomised or systematically-allocated controlled
      clinical trials comparing two or more positions in the management of infants and
      children hospitalised with acute respiratory distress. DATA COLLECTION AND
      ANALYSIS: Data were extracted from each study independently by two authors.
      Differences were resolved by consensus or referral to a third author. Continuous
      outcomes were analysed using a weighted mean difference and 95% confidence
      interval. No bivariate outcomes were available. All but one included study
      reported crossover data therefore this data was used for meta-analysis. Fixed
      effect models were used unless heterogeneity was significant (p value equal to or
      less than 0.1), in which case a random-effects model was used. MAIN RESULTS:
      Forty-nine papers were selected for this review of which 21 studies (22
      publications) were included. These studies compared prone, supine, lateral,
      elevated, and flat positions. Prone positioning was significantly more beneficial
      than supine positioning in terms of oxygen saturation, partial pressure of
      arterial oxygen, oxygenation index, thoraco-abdominal synchrony, and episodes of
      desaturation. There were no statistically significant differences between any
      other positions. AUTHORS' CONCLUSIONS: The prone position was significantly
      superior to the supine position in terms of oxygenation. However, as most
      patients included in the meta-analysis were ventilated, preterm infants the
      benefits of prone positioning may be most relevant to these infants. In addition,
      although placing infants and children in the prone position may improve
      respiratory function, the association of sudden infant death with prone
      positioning means that infants should only be placed in this position if
      continuous cardiorespiratory monitoring is used.

PMID- 15846675
TI  - Pharmacological cardioversion for atrial fibrillation and flutter.
AB  - BACKGROUND: Atrial fibrillation is the commonest cardiac dysrhythmia. It is
      associated with significant morbidity and mortality. There are two approaches to
      the management of atrial fibrillation: controlling the ventricular rate or
      converting to sinus rhythm in the expectation that this would abolish its adverse
      effects. OBJECTIVES: To assess the effects of pharmacological cardioversion of
      atrial fibrillation in adults on the annual risk of stroke, peripheral embolism,
      and mortality. SEARCH STRATEGY: We searched the Cochrane Controlled Trials
      Register (Issue 3, 2002), MEDLINE (2000 to 2002), EMBASE (1998 to 2002), CINAHL
      (1982 to 2002), Web of Science (1981 to 2002). We hand searched the following
      journals: Circulation (1997 to 2002), Heart (1997 to 2002), European Heart
      Journal (1997-2002), Journal of the American College of Cardiology (1997-2002)
      and selected abstracts published on the web site of the North American Society of
      Pacing and Electrophysiology (2001, 2002). SELECTION CRITERIA: Randomised
      controlled trials or controlled clinical trials of pharmacological cardioversion
      versus rate control in adults (>18 years) with acute, paroxysmal or sustained
      atrial fibrillation or atrial flutter, of any duration and of any aetiology. DATA
      COLLECTION AND ANALYSIS: One reviewer applied the inclusion criteria and
      extracted the data. Trial quality was assessed and the data were entered into
      RevMan. MAIN RESULTS: We identified two completed studies AFFIRM (n=4060) and
      PIAF (n=252). We found no difference in mortality between rhythm control and rate
      control relative risk 1.14 (95% confidence interval 1.00 to 1.31). Both studies
      show significantly higher rates of hospitalisation and adverse events in the
      rhythm control group and no difference in quality of life between the two
      treatment groups. In AFFIRM there was a similar incidence of ischaemic stroke,
      bleeding and systemic embolism in the two groups. Certain malignant dysrhythmias
      were significantly more likely to occur in the rhythm control group. There were
      similar scores of cognitive assessment. In PIAF, cardioverted patients enjoyed an
      improved exercise tolerance but there was no overall benefit in terms of symptom
      control or quality of life. AUTHORS' CONCLUSIONS: There is no evidence that
      pharmacological cardioversion of atrial fibrillation to sinus rhythm is superior
      to rate control. Rhythm control is associated with more adverse effects and
      increased hospitalisation. It does not reduce the risk of stroke. The conclusions
      cannot be generalised to all people with atrial fibrillation. Most of the
      patients included in these studies were relatively older (>60 years) with
      significant cardiovascular risk factors.

PMID- 15846677
TI  - Recombinant versus urinary human chorionic gonadotrophin for ovulation induction
      in assisted conception.
AB  - BACKGROUND: For the last few decades urinary human chorionic gonadotrophin has
      been used to induce final follicular maturation and for triggering ovulation in
      assisted conception. Recombinant technology has allowed the production of two
      drugs that can be used for the same purpose: to mimic the endogenous luteinizing
      hormone (LH) surge. This would allow commercial production to be adjusted
      according to market requirements. In addition all urinary contaminants would also
      be removed. Hence, this would allow the safe subcutaneous administration of a
      compound with less batch-to-batch variation. However, prior to a change in
      practice, the effectiveness of the recombinant drugs should be known, compared to
      the currently used urinary human chorionic gonadotrophins. OBJECTIVES: To assess
      the safety and efficacy of subcutaneous rhCG and high dose rLH compared with
      intramuscular uhCG for inducing final oocyte maturation and triggering ovulation.
      SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility
      Group trials register (27 August 2003), the Cochrane Central Register of
      Controlled Trials (CENTRAL on The Cochrane Library, issue 4, 2003), MEDLINE (1966
      to Feb 2004) and EMBASE (1980 to Feb 2004). Searches were not limited by
      language. The bibliographies of included, excluded trials and abstracts of major
      meetings were searched for additional trials. Authors and pharmaceutical
      companies were contacted for missing and unpublished data. SELECTION CRITERIA:
      Two reviewers independently scanned titles and abstracts, and selected those that
      appeared relevant for collection of the full paper. Only truly randomised
      controlled trials comparing rhCG or high dose r-LH with urinary hCG for
      triggering ovulation in assisted conception for treatment of infertility in
      normogonadotrophic women were included. DATA COLLECTION AND ANALYSIS: Assessment
      of inclusion/exclusion, quality assessment and data extraction were performed
      independently by at least two reviewers. Discrepancies were discussed in the
      presence of a third reviewer and a consensus reached. Quality assessment included
      method of randomisation, allocation concealment, blinding of participants and
      assessors, reporting of a power calculation, intention to treat analysis, and
      handling of dropouts. Data extraction included characteristics of participants,
      the intervention and control procedures, and outcomes. MAIN RESULTS: Seven RCTs
      were identified, four comparing rhCG and uhCG and three comparing rhLH and uhCG.
      There was no statistically significant difference between rhCG vs uhCG regarding
      the ongoing pregnancy/ live birth rate (OR 0.98, 95% CI 0.69 to 1.39), pregnancy
      rate, miscarriage or incidence of OHSS. There was no statistically significant
      difference between rhLH vs uhCG regarding the ongoing pregnancy/ live birth rate
      (OR 0.94, 95% CI 0.50 to 1.76), pregnancy rate, miscarriage or incidence of OHSS.
      The manufacturer of rhLH has decided not to further develop this product. rhCG
      was associated with a reduction in the incidence of local site reactions and
      other minor adverse effects (OR 0.47, 95% CI 0.32 to 0.70). AUTHORS' CONCLUSIONS:
      There is no evidence of difference in clinical outcomes between urinary and
      recombinant gonadotrophins for induction of final follicular maturation.
      Additional factors should be considered when choosing gonadotrophin type,
      including safety, cost and drug availability.

PMID- 15846676
TI  - Tubal flushing for subfertility.
AB  - BACKGROUND: A possible therapeutic effect of diagnostic tubal patency testing has
      been debated in the literature for half a century. Further debate surrounds
      whether oil-soluble or water-soluble contrast media might have the bigger
      fertility-enhancing effect. Historically a variety of agents have been used to
      'flush' the fallopian tubes, although tubal flushing does not currently form part
      of routine practice in the treatment of fertility delay. OBJECTIVES: To evaluate
      the effect of flushing a woman's fallopian tubes with oil- or water-soluble
      contrast media on subsequent fertility outcomes in couples with infertility.
      SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility
      Group's specialised register of trials (searched 2 March 2004), MEDLINE (1966 to
      Mar 2004), EMBASE (1980 to Mar 2004), Biological Abstract (1980 to Mar 2004) and
      reference lists of articles. SELECTION CRITERIA: All randomised trials where
      tubal flushing with oil-soluble contrast media or tubal flushing with water
      soluble media was compared with one another or with no treatment were considered
      for inclusion in the review. DATA COLLECTION AND ANALYSIS: Eleven randomised
      controlled trials were identified and included in this review. All trials were
      assessed for quality criteria. The studied primary outcome was live birth (and
      ongoing pregnancy), with secondary outcomes pregnancy, miscarriage, ectopic
      pregnancy, treatment complications including pain, intravasation of contrast
      medium, infection and haemorrhage, and image quality. MAIN RESULTS: Tubal
      flushing with oil-soluble media versus no intervention (three trials including
      381 participants) was associated with a significant increase in the odds of live
      birth (Peto OR 2.98, 95%CI 1.40 to 6.37) and of pregnancy (Peto OR 3.30, 95%CI
      2.00 to 5.43). There were no data from RCTs to assess tubal flushing with water
      soluble media versus no intervention. For the comparison of tubal flushing with
      oil-soluble media versus tubal flushing with water-soluble media (six trials
      including 1,483 participants), the increase in the odds of live birth for tubal
      flushing with oil-soluble versus water-soluble media (Peto OR 1.49, 95%CI 1.05 to
      2.11) was based on two trials where statistical heterogeneity was present and the
      higher quality trial showed no significant difference; there was no evidence of a
      significant difference in the odds of pregnancy (Peto OR 1.24, 95%CI 0.97 to
      1.57). The addition of oil-soluble media to flushing with water-soluble media
      (water-soluble plus oil-soluble media versus water-soluble media alone; three
      trials including 555 participants) showed no evidence of a significant difference
      in the odds of pregnancy (Peto OR 1.18, 95%CI 0.82 to 1.70) or live birth (Peto
      OR 1.06, 95%CI 0.64 to 1.77). Adverse event data were only available for the
      comparison OSCM versus WSCM: OSCM carried a significantly higher chance of
      intravasation (Peto OR 5.41, 95%CI 2.57 to 11.37) but a significantly lower
      chance of immediate pain (Peto OR 0.53, 95%CI 0.34 to 0.84), prolonged pain (Peto
      OR 0.26, 95%CI 0.15 to 0.45) and post-procedure bleeding (Peto OR 0.22, 95%CI
      0.15 to 0.31), and no serious adverse events were reported. AUTHORS' CONCLUSIONS:
      There is evidence of effectiveness of tubal flushing with oil-soluble contrast
      media in increasing the odds of pregnancy and live birth versus no intervention.
      The limited evidence of an increase in the odds of live birth from tubal flushing
      with oil-soluble contrast media versus water-soluble contrast media must be
      interpreted cautiously. Further robust randomised trials, comparing oil-soluble
      versus water-soluble media and comparing water-soluble media versus no
      intervention, would be a useful further guide to clinical practice. Further
      research is merited to ascertain the mechanism of the fertility enhancing effect
      of oil-soluble media, as to whether this is a 'tubal flushing' phenomenon, an
      effect on the intraperitoneal environment, or an implantation enhancing effect on
      the endometrium.

PMID- 15846678
TI  - Olanzapine IM or velotab for acutely disturbed/agitated people with suspected
      serious mental illnesses.
AB  - BACKGROUND: People presenting with agitated or violent behaviour thought to be
      due to severe mental illness may require urgent pharmacological tranquillisation.
      Several preparations of olanzapine, an antipsychotic drug, are now being used for
      management of such agitation. OBJECTIVES: To estimate the effects of
      intramuscular, oral-velotab, or standard oral olanzapine compared with other
      treatments for controlling aggressive behaviour or agitation thought to be due to
      severe mental illness. SEARCH STRATEGY: We searched the Cochrane Controlled
      Trials Register (Issue 1, 2002), The Cochrane Schizophrenia Group's Register
      (November 2004) and reference lists. We contacted authors of trials and the
      manufacturers of olanzapine. SELECTION CRITERIA: Randomised clinical trials
      comparing oral-velotab or intramuscular, or standard oral olanzapine to any
      treatment, for agitated or aggressive people with severe mental illnesses. DATA
      COLLECTION AND ANALYSIS: We reliably selected, quality assessed and data
      extracted studies. For binary outcomes we calculated a fixed effects Risk Ratio
      (RR) and its 95% Confidence Interval (CI) with a weighted Number Needed to
      Treat/Harm statistic (NNT/H). For continuous outcomes, we preferred endpoint data
      to change data and synthesised non-skewed data from valid scales using a weighted
      mean difference (WMD). MAIN RESULTS: Four trials compared olanzapine IM with IM
      placebo (total n=769, 217 allocated to placebo). Fewer people given olanzapine IM
      had 'no important response' by 2 hours compared with placebo (4 RCTs, n=769, RR
      0.49 CI 0.42 to 0.59, NNT 4 CI 3 to 5) and olanzapine IM was as acceptable as
      placebo (2 RCTs, n=354, RR leaving the study early 0.31 CI 0.06 to 1.55). When
      compared with placebo, people given olanzapine IM required substantially fewer
      additional injections following the initial dose (4 RCTs, n=774, RR 0.48 CI 0.40
      to 0.58, NNT 4 CI 4 to 5). Olanzapine IM did not seem associated with
      extrapyramidal effects (4 RCT, n=570, RR experiencing any adverse event requiring
      anticholinergic medication in first 24 hours 1.27 CI 0.49 to 3.26). Two trials
      compared olanzapine IM with haloperidol IM (total n=482, 166 allocated to
      haloperidol). Studies found no differences between olanzapine IM and haloperidol
      by 2 hours for the outcome of 'no important clinical response' (2 RCTs, n= 482,
      RR 1.00 CI 0.73 to 1.38) neither was there a difference for needing repeat IM
      injections (2 RCTs, n=482, RR 0.99 CI 0.71 to 1.38). More people on haloperidol
      experienced akathisia over the five day oral period compared with olanzapine IM
      (1 RCT, n=257, RR 0.51 CI 0.32 to 0.80, NNT 6 CI 5 to 15) and fewer people
      allocated to olanzapine IM required anticholinergic medication by 24 hours
      compared with those given haloperidol IM (2 RCTs, n= 432, RR 0.20 CI 0.09 to
      0.44, NNT 8 CI 7 to 11). Two trials compared olanzapine IM with lorazepam IM
      (total n=355, 119 allocated to lorazepam). For the outcome of 'no important
      clinical response' , there was no difference between people given olanzapine IM
      and those allocated to lorazepam at 2 hours (2 RCTs, n=355, RR 92 CI 0.66 to
      1.30) but fewer people allocated to olanzapine IM required additional injections
      by 24 hours compared with those on lorazepam IM (2 RCTs, n=355, RR 0.68 CI 0.49
      to 0.95, NNT 10 CI 6 to 59). People receiving IM olanzapine were less likely to
      experience any treatment emergent adverse events, than those on lorazepam (1 RCT,
      n=150, RR at 24 hours 0.62 CI 0.43 to 0.89, NNT 5 CI 4 to 17) and over the same
      time period there were no clear differences in the use of anticholinergic
      medication between groups (1 RCT, n=150, RR 1.16 CI 0.38 to 3.58).No studies
      reported outcomes related to hospital and service use. Nor did any report on
      issues of satisfaction with care or suicide, self-harm or harm to others. No
      studies evaluated the oro-dispersable form of olanzapine. AUTHORS' CONCLUSIONS:
      Data relevant to the effects of olanzapine IM are taken from some studies that
      may not be considered ethical in many places, all are funded by a company with a
      pecuniary interest in the result. These studies often poorly report outcomes that
      are difficult to interpret for routine care. Other important outcomes are not
      recorded at all. Nevertheless, olanzapine IM probably has some value in helping
      manage acute aggression or agitation, especially where it is necessary to avoid
      some of the older, better, known treatments. Olanzapine causes fewer movement
      disorders than haloperidol and more than lorazepam. The value of the oro
      dipersable velotab preparation is untested in trials. There is a need for well
      designed, conducted and reported randomised studies in this area. Such studies
      are possible and, we argue, should be designed with the patient groups and
      clinicians in mind. They should report outcomes of relevance to the management of
      people at this difficult point in their illness.

PMID- 15846679
TI  - Universal neonatal hearing screening versus selective screening as part of the
      management of childhood deafness.
AB  - BACKGROUND: The principal factors that decide how deafness affects a child's
      development are the degree of hearing impairment and the age at which it is
      diagnosed. A number of factors are thought to increase the risk of hearing
      impairment: low birth weight, prematurity, perinatal hypoxia and jaundice, among
      others. The high incidence of deafness in children without risk factors and the
      introduction of simple new screening tests of high sensitivity and specificity
      has led many prestigious bodies to recommend universal early detection programmes
      for deafness rather than screening targeted only at high-risk groups. OBJECTIVES:
      To compare the long-term effectiveness of a universal neonatal screening and
      early treatment programme for hearing impairment with: a) screening and treatment
      only of high-risk neonates and b) opportunistic screening and treatment. SEARCH
      STRATEGY: Databases searched were MEDLINE (1966 to 2003), EMBASE (1974 to 2003),
      the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library Issue 1, 2004) and registers of health technology assessment agencies as
      well as registers of clinical guidelines. SELECTION CRITERIA: Randomised
      controlled trials comparing universal neonatal screening with either high-risk
      screening or opportunistic screening for hearing impairment. DATA COLLECTION AND
      ANALYSIS: Two review authors independently screened the search results to
      identify suitable trials. MAIN RESULTS: No studies were identified which
      fulfilled the inclusion criteria. AUTHORS' CONCLUSIONS: The long-term
      effectiveness of universal newborn hearing screening programmes has not been
      established to date. There is a need for controlled trials and before and after
      studies to address this issue further.

PMID- 15846680
TI  - Cognitive-behavioural training interventions for assisting foster carers in the
      management of difficult behaviour.
AB  - BACKGROUND: The provision of training for foster carers is now seen as an
      important factor contributing to the successful outcome of foster care
      placements. It is believed to be associated with enhancing caring attitudes and
      skills, reducing behaviour problems in foster children, improving relationships
      between foster carers and child welfare agencies, and decreasing foster carer
      attrition. Since the late 1960s, foster carer training programs have
      proliferated, and few of the many published and unpublished training curricula
      have been systematically assessed and evaluated. The advent of cognitive
      behavioural therapy (CBT) and the research evidence demonstrating its
      effectiveness as a psychotherapeutic treatment of choice, has prompted many
      working in the social care field to devise CBT-based training programmes. CBT
      approaches to foster care training derive from a 'skill-based' training format
      that also seeks to identify and correct problematic thinking patterns that are
      associated with dysfunctional behaviour by changing and/or challenging
      maladaptive thoughts and beliefs. OBJECTIVES: To assess the effectiveness of
      cognitive-behavioural training interventions in improving a) looked-after
      children's behavioural/relationship problems, b) foster carers' psychological
      well-being and functioning, c) foster family functioning, d) foster agency
      outcomes. SEARCH STRATEGY: We searched databases including: CENTRAL (Cochrane
      Library Issue 2, 2004), MEDLINE (January 1966 to April 2004), EMBASE (January
      1980 to April 2004), CINAHL (January 1982 to April 2004), PsycINFO (January 1872
      to April 2004), ASSIA (January 1987 to April 2004), LILACS (up to April 2004),
      ERIC (January 1965 to April 2004), Sociological Abstracts (January 1963 to April
      2004), and the National Research Register 2004 (Issue 1). We contacted experts in
      the field concerning current research. SELECTION CRITERIA: All studies in which
      participants were foster parents/carers, and who were allocated by random or
      quasi-random methods to a CBT-based training intervention (in a group and/or one
      to-one settings) versus a no-treatment or wait-list control, were selected. DATA
      COLLECTION AND ANALYSIS: Results from the five eligible trials (total n = 443 )
      are reported narratively. Due to the diversity of measures employed, no meta
      analysis was performed. MAIN RESULTS: Training interventions evaluated to date
      appear to have very little effect on outcomes relating to looked-after children,
      assessed in relation to psychological functioning, extent of behavioural problems
      and interpersonal functioning. Results relating to foster carer(s) outcomes
      indicate some improvements in measures of behavioural management skills,
      attitudes and psychological functioning. Analysis pertaining to fostering agency
      outcomes did not show any significant results. AUTHORS' CONCLUSIONS: Inconclusive
      evidence exists about the efficacy of CBT-based training intervention for foster
      carers. The need for further research in this area is highlighted.

PMID- 15846681
TI  - Glucocorticosteroids for primary biliary cirrhosis.
AB  - BACKGROUND: Primary biliary cirrhosis is a chronic progressive cholestatic liver
      disease of presumed autoimmune etiology, characterised by the destruction of
      small intrahepatic bile ducts and the eventual development of cirrhosis and liver
      failure. Its progression may be influenced by immunosuppression.
      Glucocorticosteroids are potent immunosuppressive agents, but they are associated
      with significant adverse effects, including osteoporosis. OBJECTIVES: To
      systematically evaluate the beneficial and harmful effects of
      glucocorticosteroids versus placebo or no intervention for patients with primary
      biliary cirrhosis. SEARCH STRATEGY: The Cochrane Hepato-Biliary Controlled Trials
      Register,The Cochrane Library, MEDLINE, EMBASE, and the full text of the
      identified studies were searched until June 2004. The search strategy included
      terms for primary biliary cirrhosis and glucocorticosteroids (including the names
      of frequently used preparations). Previous research groups and manufacturers were
      contacted for additional references. No language restrictions were applied.
      SELECTION CRITERIA: Double-blind, single-blind, or unblinded randomised clinical
      trials evaluating any preparation of glucocorticosteroids versus placebo or no
      intervention in patients with primary biliary cirrhosis diagnosed by abnormal
      liver function tests and either anti-mitochondrial antibodies or histology were
      included. Additional agents were allowed if they were administered to both groups
      equally. DATA COLLECTION AND ANALYSIS: The quality of the randomised clinical
      trials was evaluated by methodology components (generation of allocation
      sequence; allocation concealment; blinding; follow up). Analyses were performed
      according to the intention-to-treat method with missing data being accounted for
      by imputation. MAIN RESULTS: Only two underpowered trials (reporting 36 and 40
      patients) were identified. These differed markedly in their inclusion criteria
      and treatment protocols. Both stated that they used placebo. However, allocation
      concealment was unclear. Only one trial reported any patient deaths. No
      significant improvement in mortality was identified (odds ratio (OR) 0.42, 95%
      confidence interval (CI) 0.10 to 1.76). Improvements in serum markers of liver
      inflammation and liver histology were identified. Potentially prognostically
      linked markers such as bilirubin and albumin were incompletely reported. Bone
      mineral density (weighted mean difference -2.84%, 95% CI -4.16 to -1.53) and the
      number of patients with any adverse event (OR 8.99, 95% CI 2.15 to 37.58) were
      significantly increased in the glucocorticosteroid group. AUTHORS' CONCLUSIONS:
      There is insufficient data to support or reject the use of glucocorticosteroids
      for patients with primary biliary cirrhosis. It may be appropriate to consider a
      large prospective randomised clinical trial on this topic.

PMID- 15846682
TI  - Argon plasma coagulation therapy for acute non-variceal upper gastrointestinal
      bleeding.
AB  - BACKGROUND: Endoscopic treatment is recommended for initial hemostasis in non
      variceal upper gastrointestinal bleeding. Many endoscopic hemostatic devices are
      used. Argon Plasma Coagulation (APC) is an alternative. OBJECTIVES: This study
      reviews all available literature to access the efficacy of APC compared to other
      endoscopic therapies in the control of acute non-variceal upper GI hemorrhage.
      SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (The Cochrane Library Issue 4 2003), MEDLINE 1966 to December 2003, EMBASE 1980
      to December 2003, Web of Science for SCISEARCH (1980 to December 2003), BIOSIS
      (1985 to December 2003), and the National Research Register Issue 4 2003. We also
      handsearched abstracts from conference proceedings of the United European
      Gastroenterology Week and Digestive Disease Week. SELECTION CRITERIA: Randomized,
      controlled trials of APC compared with other endoscopic hemostasis interventions
      in the treatment of non-variceal upper gastrointestinal bleeding. DATA COLLECTION
      AND ANALYSIS: Two reviewers assessed trial quality and independently extracted
      data. MAIN RESULTS: Two trials involving 121 people were included. There was no
      common intervention to pool. One trial compared APC to heat probe, another trial
      compared APC to injection sclerotherapy. There was no significant difference
      between groups in either of these trials. AUTHORS' CONCLUSIONS: On the basis of
      the two randomised controlled trials identified in this review, there is no
      evidence to suggest that APC is superior to other endoscopic therapies. Further
      randomised controlled trials are needed.

PMID- 15846683
TI  - Psychological interventions for overweight or obesity.
AB  - BACKGROUND: Overweight and obesity are global health problems which are
      increasing throughout the industrialised world. If left unchecked, they will
      continue to contribute to the ever increasing noncommunicable disease burden.
      OBJECTIVES: To assess the effects of psychological interventions for overweight
      or obesity as a means of achieving sustained weight loss. SEARCH STRATEGY:
      Studies were obtained from searches of multiple electronic bibliographic
      databases. The date of the latest search was June 2003. SELECTION CRITERIA:
      Trials were included if the fulfilled the following criteria: 1) they were
      randomised controlled clinical trials of a psychological intervention versus a
      comparison intervention, 2) one of the outcome measures of the study was weight
      change measured by any method, 3) participants were followed for at least three
      months, 4) the study participants were adults (18 years or older) who were
      overweight or obese (BMI > 25 kg/m(2)) at baseline. DATA COLLECTION AND ANALYSIS:
      Two people independently applied the inclusion criteria to the studies identified
      and assessed study quality. Disagreement was resolved by discussion or by
      intervention of a third party. Meta-analyses were performed using a fixed effect
      model. MAIN RESULTS: A total of 36 studies met the inclusion criteria and were
      included in the review. Overall, 3495 participants were evaluated. The majority
      of studies assessed behavioural and cognitive-behavioural weight reduction
      strategies. Cognitive therapy, psychotherapy, relaxation therapy and hypnotherapy
      were assessed in a small number of studies. Behaviour therapy was found to result
      in significantly greater weight reductions than placebo when assessed as a stand
      alone weight loss strategy (WMD -2.5 kg; 95% CI -1.7 to -3.3). When behaviour
      therapy was combined with a diet / exercise approach and compared with diet /
      exercise alone, the combined intervention resulted in a greater weight reduction.
      Studies were heterogeneous however the majority of studies favoured combining
      behaviour therapy with dietary and exercise interventions to improve weight loss.
      Increasing the intensity of the behavioural intervention significantly increased
      the weight reduction (WMD -2.3 kg; 95% CI -1.4 to - 3.3). Cognitive-behaviour
      therapy, when combined with a diet / exercise intervention, was found to increase
      weight loss compared with diet / exercise alone (WMD -4.9 kg; 95% CI -7.3 to -
      2.4). No data on mortality, morbidity or quality of life were found. AUTHORS'
      CONCLUSIONS: People who are overweight or obese benefit from psychological
      interventions, particularly behavioural and cognitive-behavioural strategies, to
      enhance weight reduction. They are predominantly useful when combined with
      dietary and exercise strategies. The bulk of the evidence supports the use of
      behavioural and cognitive-behavioural strategies. Other psychological
      interventions are less rigorously evaluated for their efficacy as weight loss
      treatments.

PMID- 15846684
TI  - Red-light cameras for the prevention of road traffic crashes.
AB  - BACKGROUND: Road crashes are a prime cause of death and disability and red-light
      running is a common cause of crashes at signalised intersections. Red-light
      cameras are increasingly used to promote compliance with traffic signals. Manual
      enforcement methods are resource intensive and high risk, whereas red-light
      cameras can operate 24 hours a day and do not involve high-speed pursuits.
      OBJECTIVES: To quantify the impact of red-light cameras on the incidence and
      severity of road crashes and casualties, and the incidence of red-light
      violations. SEARCH STRATEGY: We searched the following electronic databases:
      TRANSPORT (NTIS, TRIS, IRRD,TRANSDOC), Cochrane Injuries Group Specialised
      Register, Cochrane Controlled Trials Register, MEDLINE, EMBASE and the Australian
      Transport Index. We checked the reference lists of relevant papers and contacted
      research and advocacy organisations. SELECTION CRITERIA: Randomised or quasi
      controlled trials and controlled before-after studies of red-light cameras. For
      crash impact evaluation, the before and after periods each had to be at least one
      year in length. For violation studies, the after period had to occur at least one
      year after camera installation. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently extracted data on study type, characteristics of camera and control
      areas, and data collection period. Before-after data were collected on number of
      crashes by severity, collision type, deaths and injuries, and red-light
      violations. Rate ratio was calculated for each study. Where there was more than
      one, rate ratios were pooled to give an overall estimate, using a generic inverse
      variance method and a random-effects model. MAIN RESULTS: No randomised
      controlled trials were identified but 10 controlled before-after studies from
      Australia, Singapore and the USA met our inclusion criteria. We grouped them
      according to the extent to which they adjusted for regression to the mean (RTM)
      and spillover effects. Total casualty crashes: the only study that adjusted for
      both reported a rate ratio of 0.71 (95% CI to 0.55, 0.93); for three that
      partially adjusted for RTM but failed to consider spillover, rate ratio was 0.87
      (95% CI to 0.77, 0.98); one that made no adjustments had a rate ratio of 0.80
      (95% CI 0.58 to 1.12). Right-angle casualty crashes: rate ratio for two studies
      that partially addressed RTM was 0.76 (95% CI 0.54 to 1.07). Total crashes: the
      study addressing both RTM and spillover reported a rate ratio of 0.93 (95% CI
      0.83 to 1.05); one study that partially addressed RTM had a rate ratio of 0.92
      (95% CI 0.73 to 1.15); the pooled rate ratio from the five studies with no
      adjustments was 0.74 (95% CI 0.53 to 1.03). Red-light violations: one study found
      a rate ratio of 0.53 (95% CI 0.17 to 1.66). AUTHORS' CONCLUSIONS: Red-light
      cameras are effective in reducing total casualty crashes. The evidence is less
      conclusive on total collisions, specific casualty collision types and violations,
      where reductions achieved could be explained by the play of chance. Most
      evaluations did not adjust for RTM or spillover, affecting their accuracy. Larger
      and better controlled studies are needed.

PMID- 15846685
TI  - Sedation of anxious children undergoing dental treatment.
AB  - BACKGROUND: Anxiety about dental treatment maybe a barrier to its uptake in
      children. Sedation can be used to relieve anxiety and manage behaviour,
      unfortunately it is difficult to determine from published research which agents,
      dosages and techniques are effective. OBJECTIVES: To evaluate the relative
      efficacy of the various conscious sedation techniques and dosages for behaviour
      management in paediatric dentistry. SEARCH STRATEGY: Computerised: MEDLINE,
      PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Dissertation
      Abstracts, SIGLE, the World Wide Web (Google) and the Community of Science
      Database were searched for relevant trials and references. Searches were carried
      out for MEDLINE and EMBASE up to June 2003 and for the remaining databases
      December 2002. Reference lists from relevant articles were scanned and the
      authors contacted to identify trials and obtain additional information. There
      were no language restrictions. Trials pre-1966 were not searched. SELECTION
      CRITERIA: Studies were selected if they met the following criteria: randomised
      controlled trials of conscious sedation comparing two or more
      drugs/techniques/placebo undertaken by the dentist or one of the dental team in
      anxious children up to 16 years of age. DATA COLLECTION AND ANALYSIS: Information
      regarding methods, participants, interventions and outcome measures and results
      were independently extracted, in duplicate, by two authors. Specialist advice was
      asked to categorise interventions. Authors of trials were contacted for details
      of randomisation and withdrawals and a quality assessment was carried out not
      using any formal scoring system. The Cochrane Oral Health Group statistical
      guidelines were followed. MAIN RESULTS: Fifty-three studies were included with
      2345 subjects in total. Overall quality of studies was found to be disappointing
      with poor reporting often the main problem. Data reported could not be easily
      aggregated into groups to facilitate description of results. Meta-analysis of the
      available data was also not possible for the same reason. The variety of
      differing drug regimens compared made it difficult to isolate groups of studies
      that were sufficiently similar in design to allow sensible comparison. Where
      groups of studies could be isolated, then the differing outcome measures used
      made their meta-analysis impossible. AUTHORS' CONCLUSIONS: Authors were not able
      to reach any definitive conclusion on which was the most effective drug or method
      of sedation used for anxious children. A list of proposed areas of study was
      described.

PMID- 15846686
TI  - Interventions for treating asymptomatic impacted wisdom teeth in adolescents and
      adults.
AB  - BACKGROUND: The prophylactic removal of asymptomatic impacted wisdom teeth is
      defined as the (surgical) removal of wisdom teeth in the absence of local
      disease. Impacted wisdom teeth have been associated with pathological changes,
      such as inflammation of the gums around the tooth, root resorption, gums- and
      alveolar bone disease, damage of the adjacent teeth, the development of cysts and
      tumours. Several other reasons to justify prophylactic removal have also been
      given. Wisdom teeth do not always fulfil a functional role in the mouth. When
      surgical removal is carried out in older patients the risk of more postoperative
      complications, pain and discomfort increases. Nevertheless, in most developed
      countries the prophylactic removal of trouble-free wisdom teeth, either impacted
      or fully erupted, has long been considered as 'appropriate care'. Prudent
      decision-making, with adherence to specified indicators for removal, may reduce
      the number of surgical procedures by 60% or more. It has been suggested that
      watchful monitoring of asymptomatic wisdom teeth may be an appropriate strategy.
      OBJECTIVES: To evaluate the effect of prophylactic removal of asymptomatic
      impacted wisdom teeth in adolescents and adults compared with the retention of
      these wisdom teeth. SEARCH STRATEGY: The following electronic databases were
      searched:The Cochrane Oral Health Group Trials Register (4 August 2004), the
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 4
      August 2004), PubMed (1966 to 4 August 2004), EMBASE (1974 to 4 August 2004).
      There was no restriction on language. Key journals were handsearched. An attempt
      was made to identify ongoing and unpublished trials. SELECTION CRITERIA: All
      randomised or controlled clinical trials (RCTs/CCTs) comparing the effect of
      prophylactic removal of asymptomatic impacted wisdom teeth with no-treatment
      (retention). DATA COLLECTION AND ANALYSIS: Assessment of relevance, validity and
      data extraction were conducted in duplicate and independently by three reviewers.
      Where uncertainty existed, authors were contacted for additional information
      about randomisation and withdrawals. A quality assessment of the trials was
      carried out. MAIN RESULTS: Only three trials were identified that satisfied the
      review selection criteria. Two were completed RCTs and both assessed the
      influence of prophylactic removal on late incisor crowding in adolescents. One
      ongoing RCT was identified, but the researchers were unable to provide any data.
      They intend to publish in the near future and information received will be
      included in updates. Although both completed trials met the inclusion criteria of
      the review, regarding participants characteristics, interventions and outcomes
      assessed, different outcomes measures were assessed which prevented pooling of
      data. AUTHORS' CONCLUSIONS: No evidence was found to support or refute routine
      prophylactic removal of asymptomatic impacted wisdom teeth in adults. There is
      some reliable evidence that suggests that the prophylactic removal of
      asymptomatic impacted wisdom teeth in adolescents neither reduces nor prevents
      late incisor crowding.

PMID- 15846687
TI  - Inhaled magnesium sulfate in the treatment of acute asthma.
AB  - BACKGROUND: Asthma exacerbations can be frequent and range in severity from
      relatively mild to status asthmaticus. The use of magnesium sulfate (MgSO4) is
      one of numerous treatment options available during acute exacerbations. While the
      efficacy of intravenous MgSO4 has been demonstrated, little is known about
      inhaled MgSO4. OBJECTIVES: To examine the efficacy of inhaled MgSO4 in the
      treatment asthma exacerbations. SEARCH STRATEGY: Randomised controlled trials
      were identified from the Cochrane Airways Group "Asthma and Wheez*" register.
      These trials were supplemented with trials found in the reference list of
      published studies, studies found using extensive electronic search techniques, as
      well as a review of the gray literature and conference proceedings. SELECTION
      CRITERIA: Randomised (or pseudo-randomised) controlled trials were eligible for
      inclusion. Studies were included if patients were treated with nebulised MgSO4
      alone or in combination with beta2-agonist and where compared to beta2-agonist
      alone or inactive control. DATA COLLECTION AND ANALYSIS: Trial selection, data
      extraction and methodological quality were assessed by two independent reviewers.
      Efforts were made to collect missing data from authors. Results from fixed
      effects models are presented as standardized mean differences (SMD) for pulmonary
      functions and relative risks (RR) for hospital admission; both are displayed with
      their 95% confidence intervals (95% CI). MAIN RESULTS: Six trials involving 296
      patients were included. Four studies compared nebulised MgSO4 with beta2-agonist
      to beta2-agonist and two studies compared MgSO4 to beta2-agonist alone. Three
      studies enrolled only adults and 2 enrolled exclusively pediatric patients; three
      of the studies enrolled severe asthmatics. Overall, there was a significant
      difference in pulmonary function between patients whose treatments included
      nebulised MgSO4 in addition to beta2-agonist (SMD: 0.37; 95% CI: 0.1 to 0.63; 4
      studies); however, hospitalizations were similar between the groups (RR: 0.64;
      95% CI: 0.40 to 1.04; 3 studies). Subgroup analyses did not demonstrate
      significant differences in lung function improvement between adults and children,
      or between severe and mild to moderate asthmatics. Conclusions regarding
      treatment with nebulised MgSO4 alone are difficult to draw due to lack of studies
      in this area. AUTHORS' CONCLUSIONS: Nebulised inhaled magnesium sulfate in
      addition to beta2-agonist in the treatment of an acute asthma exacerbation,
      appears to have benefits with respect to improved pulmonary function and there is
      a trend towards benefit in hospital admission. Heterogeneity between trials
      included in this review precludes a more definitive conclusion.

PMID- 15846688
TI  - Cephalic version by moxibustion for breech presentation.
AB  - BACKGROUND: Moxibustion (a type of Chinese medicine which involves burning a herb
      close to the skin) to the acupuncture point Bladder 67 (BL67) (Chinese name
      Zhiyin), located at the tip of the fifth toe, has been proposed as a way of
      correcting breech presentation. As caesarean section is often suggested for
      breech babies due to the potential difficulties during labour, it is preferable
      to turn the baby before labour starts. OBJECTIVES: To examine the effectiveness
      and safety of moxibustion on changing the presentation of an unborn baby in the
      breech position, the need for external cephalic version (ECV), mode of birth, and
      perinatal morbidity and mortality for breech presentation. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group trials register (30 August
      2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library,
      Issue 1, 2004), MEDLINE (1966 to March 2004), EMBASE (1980 to March 2004), CINAHL
      (1982 to March 2004), MIDIRS (1982 to March 2004), CISCOM (9 March 2004) and
      bibliographies of relevant papers. SELECTION CRITERIA: The inclusion criteria
      were published and unpublished randomised controlled trials comparing moxibustion
      (either alone or in combination with acupuncture) with a control group (no
      moxibustion), or other methods (e.g. external cephalic version, acupuncture) in
      women with a singleton breech presentation. DATA COLLECTION AND ANALYSIS: Both
      authors assessed eligibility and quality of trials independently. The outcome
      measures were baby's presentation at birth, need for external cephalic version,
      mode of birth, perinatal morbidity and mortality, maternal complications and
      maternal satisfaction, and adverse events. MAIN RESULTS: Three trials involving a
      total of 597 women were included. Due to differences in interventions and sample
      size it was not appropriate to perform a meta-analysis for the main outcome. Only
      one trial reported on other outcome measures relevant to this review. Moxibustion
      reduced the need for ECV (relative risk (RR) 0.47, 95% confidence interval (CI)
      0.33 to 0.66) and resulted in decreased use of oxytocin before or during labour
      for women who had vaginal deliveries (RR 0.28, 95% CI 0.13 to 0.60). AUTHORS'
      CONCLUSIONS: There is insufficient evidence to support the use of moxibustion to
      correct a breech presentation. Moxibustion may be beneficial in reducing the need
      for ECV, and decreasing the use of ocytocin, however there is a need for well
      designed randomised controlled trials to evaluate moxibustion for breech
      presentation which report on clinically relevant outcomes as well as the safety
      of the intervention.

PMID- 15846689
TI  - Non-legislative interventions for the promotion of cycle helmet wearing by
      children.
AB  - BACKGROUND: Helmets reduce bicycle-related head and facial injuries for
      bicyclists of all ages in all types of crash. We aimed to identify non
      legislative interventions that are effective in promoting helmet use among
      children, so future campaigns can be designed on a firm evidence base.
      OBJECTIVES: to assess the effectiveness of non-legislative interventions
      (compared to a lack of interventions) in increasing helmet use among children; to
      identify possible reasons for differences in the effectiveness of interventions;
      to evaluate effectiveness with respect to social group; to identify any adverse
      consequences of interventions. SEARCH STRATEGY: We searched 11 electronic
      databases and manually searched other sources of potentially relevant data.
      SELECTION CRITERIA: We included randomised controlled trials, cluster randomised
      controlled trials and controlled before and after studies. Studies included
      participants aged 0 to 18 years and described interventions to promote helmet use
      not requiring enactment of legislation. Studies had to report at least one of the
      following outcomes: observed helmet wearing; self-reported helmet ownership; self
      reported helmet wearing. DATA COLLECTION AND ANALYSIS: Data were extracted by two
      reviewers working independently. Study results were adjusted to account for
      clustering. A random-effects model was used to pool data in meta-analyses.
      Heterogeneity was explored with sub-group analyses. MAIN RESULTS: Twenty-two
      studies were included. The odds of observed helmet wearing were significantly
      greater amongst those receiving non-legislative interventions (OR 2.30, 95% CI
      1.37 to 3.85). Sub-group analysis indicated the effect may be greater for
      community-based studies (OR 4.30, 95% CI 2.24 to 8.25) and those providing free
      helmets (OR 4.35, 95% CI 2.13 to 8.89) than for those providing subsidised
      helmets (OR 2.02, 95% CI 0.98 to 4.17) and for those set in schools (OR 1.82, 95%
      CI 0.94 to 3.52). We found no significant effect of non-legislative interventions
      in increasing self-reported helmet ownership, but they were associated with a
      significant increase in self-reported helmet wearing (OR 3.90, 95% CI 1.42 to
      10.69), particularly amongst interventions set in schools (OR 4.73, 95% CI 1.09
      to 20.49) but there was significant unexplained heterogeneity between effect
      sizes for these two outcomes. AUTHORS' CONCLUSIONS: Community-based studies that
      include the provision of free helmets alongside an educational component increase
      observed helmet wearing in the areas in which they are set. There is some
      evidence that interventions in schools and those providing subsidised helmets may
      increase observed helmet wearing, but possibly to a lesser extent than those set
      in communities and those providing free helmets.

PMID- 15846690
TI  - 20 mcg versus >20 mcg estrogen combined oral contraceptives for contraception.
AB  - BACKGROUND: Concern about estrogen-related adverse effects has led to progressive
      reductions in the estrogen dose in combination oral contraceptives (COCs).
      However, reducing the amount of estrogen to improve safety also could result in
      decreased contraceptive effectiveness and unacceptable changes in bleeding
      patterns. OBJECTIVES: To test the hypothesis that COCs containing </=20 mcg
      ethinyl estradiol (EE) perform similarly as those containing >20 mcg in terms of
      contraceptive effectiveness, bleeding patterns, discontinuation, and side
      effects. SEARCH STRATEGY: We searched computerized databases (CENTRAL, MEDLINE,
      EMBASE, and POPLINE) from their inception to November 2003, searched the
      references of eligible trials, and wrote to oral contraceptive manufacturers to
      identify eligible trials. SELECTION CRITERIA: English-language reports of
      randomized controlled trials that compare a COC containing </=20 mcg EE with a
      COC containing >20 mcg EE were eligible. We excluded studies where the
      interventions were designed to be administered for less than three consecutive
      cycles or to be used primarily as treatment for non-contraceptive conditions.
      Trials had to report on contraceptive effectiveness, bleeding patterns, trial
      discontinuation due to bleeding-related reasons or other side effects, or side
      effects to be included in the review. DATA COLLECTION AND ANALYSIS: The primary
      reviewer evaluated all titles and abstracts located in the literature searches to
      determine whether they met the inclusion criteria. Two reviewers independently
      extracted data from the studies identified for inclusion. We wrote to the authors
      when clarifications or additional data were needed. Data were entered and
      analyzed with RevMan 4.2. MAIN RESULTS: No differences were found in
      contraceptive effectiveness for the 11 COC pairs for which this outcome was
      reported. Several COCs containing 20 mcg EE resulted in higher rates of early
      trial discontinuation (overall and due to adverse events such as irregular
      bleeding) as well as increased risk of bleeding disturbances (both
      amenorrhea/infrequent bleeding and irregular, prolonged, frequent bleeding, or
      breakthrough bleeding or spotting) than their higher-estrogen comparison pills.
      AUTHORS' CONCLUSIONS: While COCs containing 20 mcg EE may be theoretically safer,
      this review did not focus on the rare events required to assess this hypothesis.
      Data from randomized controlled trials are inadequate to detect possible
      differences in contraceptive effectiveness. Low-dose estrogen COCs resulted in
      higher rates of bleeding pattern disruptions. However, most trials compared COCs
      containing different progestin types, and changes in bleeding patterns could be
      related to progestin type as well as estrogen dose.

PMID- 15846691
TI  - Environmental sanitary interventions for preventing active trachoma.
AB  - BACKGROUND: Trachoma is the second or third major cause of blindness. It is
      responsible for about six million blind people worldwide, mostly in the poor
      communities of developing countries. One of the major strategies advocated for
      the control of the disease is the application of various environmental sanitary
      measures to such communities. OBJECTIVES: To assess the evidence for the
      effectiveness of environmental sanitary measures on the prevalence of active
      trachoma in endemic areas. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and
      Vision Group Trials Register) on The Cochrane Library (Issue 4, 2004), MEDLINE
      (1966 to January 2005), EMBASE (1980 to January 2005), LILACS (April 2004), the
      reference list of trials and the Science Citation Index. We also contacted
      agencies, experts and researchers in trachoma control. SELECTION CRITERIA: This
      review included randomised and quasi-randomised controlled trials comparing any
      form of environmental hygiene measures with no measure. These hygienic measures
      included fly control, provision of water and health education. Participants in
      the trials were people normally resident in the trachoma endemic areas. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed
      the quality of trials. Study authors were contacted for additional information.
      Three trials met the inclusion criteria but meta-analysis was not conducted due
      to heterogeneity of the studies. MAIN RESULTS: Two studies that assessed
      insecticide spray as a fly control measure found that trachoma is reduced by at
      least 55% to 61% with this measure compared to no intervention. One study found
      that another fly control measure, latrine provision, reduced trachoma by 29.5%
      compared to no intervention; this was, however, not statistically significantly
      different. Another study revealed that health education on personal and household
      hygiene reduced the incidence of trachoma such that the odds of reducing trachoma
      in the health education village was about twice that of the no intervention
      village. However, all the studies have some methodological concerns relating to
      concealment of allocation and non-consideration of clustering effect in data
      analysis. AUTHORS' CONCLUSIONS: There is evidence that insecticide spray as a fly
      control measure reduces trachoma significantly. Latrine provision as a fly
      control measure has not demonstrated significant trachoma reduction. Health
      education may be effective in reducing trachoma. There is a dearth of data to
      determine the effectiveness of all aspects of environmental sanitation in the
      control of trachoma.

PMID- 15846692
TI  - Music therapy for schizophrenia or schizophrenia-like illnesses.
AB  - BACKGROUND: Music therapy is a psychotherapeutic method that uses musical
      interaction as a means of communication and expression. The aim of the therapy is
      to help people with serious mental illness to develop relationships and to
      address issues they may not be able to using words alone. OBJECTIVES: To review
      the effects of music therapy, or music therapy added to standard care, compared
      to placebo, standard care or no treatment for people with serious mental
      illnesses such as schizophrenia. SEARCH STRATEGY: The Cochrane Schizophrenia
      Group's Register (July 2002) was searched. This was supplemented by hand
      searching of music therapy journals, manual searches of reference lists, and
      contacting relevant authors. SELECTION CRITERIA: All randomised controlled trials
      that compared music therapy with standard care or other psychosocial
      interventions for schizophrenia. DATA COLLECTION AND ANALYSIS: Studies were
      reliably selected, quality assessed and data extracted. Data were excluded where
      more than 30% of participants in any group were lost to follow up. Non-skewed
      continuous endpoint data from valid scales were synthesised using a standardised
      mean difference (SMD). If statistical heterogeneity was found, treatment 'dosage'
      and treatment approach were examined as possible sources of heterogeneity. MAIN
      RESULTS: Four studies were included. These examined the effects of music therapy
      over the short to medium term (1 to 3 months), with treatment 'dosage' varying
      from 7 to 78 sessions. Music therapy added to standard care was superior to
      standard care alone for global state (medium term, 1 RCT, n = 72, RR 0.10 CI 0.03
      to 0.31, NNT 2 CI 1.2 to 2.2). Continuous data suggested some positive effects on
      general mental state (1 RCT, n=69, SMD average endpoint PANSS -0.36 CI -0.85 to
      0.12; 1 RCT, n=70, SMD average endpoint BPRS -1.25 CI -1.77 to -0.73),on negative
      symptoms (3 RCTs, n=180, SMD average endpoint SANS -0.86 CI -1.17 to -0.55) and
      social functioning (1 RCT, n=70, SMD average endpoint SDSI score -0.78 CI -1.27
      to -0.28). However these latter effects were inconsistent across studies and
      depended on the number of music therapy sessions. All results were for the 1-3
      month follow up. AUTHORS' CONCLUSIONS: Music therapy as an addition to standard
      care helps people with schizophrenia to improve their global state and may also
      improve mental state and functioning if a sufficient number of music therapy
      sessions are provided. Further research should address the dose-effect
      relationship and the long-term effects of music therapy.

PMID- 15846693
TI  - Acupuncture for depression.
AB  - BACKGROUND: There is interest from the community in the use of self help and
      complementary therapies for depression. This review examined the currently
      available evidence supporting the use of acupuncture to treat depression.
      OBJECTIVES: To examine the efficacy and adverse effects of acupuncture for
      depression. SEARCH STRATEGY: The following databases were searched: Cochrane
      Central Register of Controlled Trials (CENTRAL) MEDLINE (1966 to Sept 2003)
      EMBASE (1980 to Sept 2003) PSYCINFO (1874 to Sept 2003) the Database of Abstracts
      of Reviews of Effectiveness (DARE) CISCOM, CINAHL (January 1980 to Sept 2003).
      The following terms were used: depression, depressive disorder, dysthymic
      disorder and acupuncture. SELECTION CRITERIA: Inclusion criteria included all
      published and unpublished randomised controlled trials comparing acupuncture with
      sham acupuncture, no treatment, pharmacological treatment, other structured
      psychotherapies (cognitive behavioural therapy, psychotherapy or counselling), or
      standard care. The following modes of treatment were included: acupuncture,
      electro acupuncture or laser acupuncture. The subjects included adult men and
      women with depression defined by clinical state description, or diagnosed by the
      Diagnostic and Statistical Manual (DSM-IV), Research Diagnostic Criteria (RDC),
      or the International Classification of Disease (ICD). DATA COLLECTION AND
      ANALYSIS: Meta analysis was performed using relative risk for dichotomous
      outcomes and weighted mean differences for continuous outcomes, with 95%
      confidence intervals. Primary outcomes were reduction in the severity of
      depression, measured by self rating scales, or by clinician rated scales; and an
      improvement in depression defined as remission vs no remission. MAIN RESULTS:
      Seven trials comprising 517 subjects met the inclusion criteria. Five trials (409
      subjects) included a comparison between acupuncture and medication. Two other
      trials compared acupuncture with a wait list control or sham acupuncture.
      Subjects generally had mild to moderate depression. There was no evidence that
      medication was better than acupuncture in reducing the severity of depression
      (WMD 0.53, 95%CI -1.42 to 2.47), or in improving depression, defined as remission
      versus no remission (RR1.2, 95%CI 0.94 to 1.51). AUTHORS' CONCLUSIONS: There is
      insufficient evidence to determine the efficacy of acupuncture compared to
      medication, or to wait list control or sham acupuncture, in the management of
      depression. Scientific study design was poor and the number of people studied was
      small.

PMID- 15846694
TI  - Chemotherapy for advanced gastric cancer.
AB  - BACKGROUND: Gastric cancer currently ranks second in global cancer mortality.
      Most patients are either diagnosed at an advanced stage, or develop a relapse
      after apparently curative operation. Apart from supportive measures, systemic
      chemotherapy is the only treatment option available in this situation.
      OBJECTIVES: To assess the effect of chemotherapy versus best supportive care,
      combination versus single agent chemotherapy and different combination
      chemotherapy regimens in advanced gastric cancer. SEARCH STRATEGY: We searched
      the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1,
      2004), MEDLINE and EMBASE up to February 2004 and reference lists of articles. We
      also contacted pharmaceutical companies as well as national and international
      experts. SELECTION CRITERIA: Randomised controlled trials on systemic intravenous
      chemotherapy versus best supportive care, combination versus single agent
      chemotherapy and different combination chemotherapies in advanced gastric cancer.
      DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. A third
      investigator was consulted in case of disagreements. We contacted study authors
      to obtain missing information. MAIN RESULTS: Chemotherapy versus best supportive
      care consistently demonstrated a significant benefit in terms of overall survival
      in favour of the group receiving chemotherapy (Hazard Ratios (HR) 0.39; 95%
      confidence intervals (CI) 0.28 to 0.52). Combination versus single-agent
      chemotherapy provides evidence for a survival benefit in favour of combination
      chemotherapy (HR 0.85; 95% CI 0.76 to 0.96). Numbers included in these
      comparisons were 184 and 1338 participants respectively. This benefit is achieved
      at the price of increased toxicity in the combination chemotherapy arms. When
      comparing 5-FU/cisplatin-containing combination therapy regimens with
      anthracyclines versus those without anthracyclines (HR 0.77; 95% CI 0.62 to 0.95
      based on 501 participants) and 5-FU/anthracycline-containing combinations with
      cisplatin versus those without cisplatin (HR 0.83; 95% CI 0.76 to 0.91 based on
      1147 participants), there was a significant survival benefit for regimens
      including 5-FU, anthracyclines and cisplatin. AUTHORS' CONCLUSIONS: Chemotherapy
      significantly improves survival in comparison to best supportive care. In
      addition, combination chemotherapy improves survival compared to single-agent 5
      FU, but the effect size is much smaller. Among the combination chemotherapy
      regimens studied, best survival results are achieved with regimens containing 5
      FU, anthracyclines and cisplatin. In this category, ECF (epirubicin, cisplatin
      and continuous infusion 5-FU) is tolerated best.

PMID- 15846695
TI  - Vitamin E supplementation in pregnancy.
AB  - BACKGROUND: Vitamin E supplementation may help reduce the risk of pregnancy
      complications involving oxidative stress, such as pre-eclampsia. There is a need
      to evaluate the efficacy and safety of vitamin E supplementation in pregnancy.
      OBJECTIVES: To assess the effects of vitamin E supplementation, alone or in
      combination with other separate supplements, on pregnancy outcomes, adverse
      events, side-effects and use of health services. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group Trials Register (23 June 2004), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2,
      2004), MEDLINE (1966 to May 2004), Current Contents (1998 to May 2004) and EMBASE
      (1980 to May 2004). SELECTION CRITERIA: All randomised or quasi-randomised
      controlled trials evaluating vitamin E supplementation in pregnant women. We
      excluded interventions using a multivitamin supplement that contained vitamin E.
      DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for
      inclusion, extracted data and assessed trial quality. MAIN RESULTS: Four trials,
      involving 566 women either at high risk of pre-eclampsia or with established pre
      eclampsia, were eligible for this review. All trials assessed vitamin E in
      combination with other supplements and two trials were published in abstract form
      only. No difference was found between women supplemented with vitamin E in
      combination with other supplements during pregnancy compared with placebo for the
      risk of stillbirth (relative risk (RR) was 0.77, 95% confidence intervals (CI)
      0.35 to 1.71, two trials, 339 women), neonatal death (RR 5.00, 95% CI 0.64 to
      39.06, one trial, 40 women), perinatal death (RR 1.29, 95% CI 0.67 to 2.48, one
      trial, 56 women), preterm birth (RR 1.29, 95% CI 0.78 to 2.15, two trials, 383
      women), intrauterine growth restriction (RR 0.72, 95% CI 0.49 to 1.04, two
      trials, 383 women) or birthweight (weighted mean difference -139.00 g, 95% CI 
      517.68 to 239.68, one trial, 100 women), using fixed-effect models. Substantial
      heterogeneity was found for pre-eclampsia. Women supplemented with vitamin E in
      combination with other supplements compared with placebo were at decreased risk
      of developing clinical pre-eclampsia (RR 0.44, 95% CI 0.27 to 0.71, three trials,
      510 women) using fixed-effect models; however, this difference could not be
      demonstrated when using random-effects models (RR 0.44, 95% CI 0.16 to 1.22,
      three trials, 510 women). There were no differences between women supplemented
      with vitamin E compared with placebo for any of the secondary outcomes. AUTHORS'
      CONCLUSIONS: The data are too few to say if vitamin E supplementation either
      alone or in combination with other supplements is beneficial during pregnancy.

PMID- 15846696
TI  - Vitamin C supplementation in pregnancy.
AB  - BACKGROUND: Vitamin C supplementation may help reduce the risk of pregnancy
      complications like pre-eclampsia, intrauterine growth restriction and maternal
      anaemia. There is a need to evaluate the efficacy and safety of vitamin C
      supplementation in pregnancy. OBJECTIVES: To evaluate the effects of vitamin C
      supplementation, alone or in combination with other separate supplements, on
      pregnancy outcomes, adverse events, side-effects and use of health resources.
      SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials
      Register (23 June 2004), Cochrane Central Register of Controlled Trials (The
      Cochrane Library, Issue 2, 2004), MEDLINE, Current Contents and EMBASE. SELECTION
      CRITERIA: All randomised or quasi-randomised controlled trials evaluating vitamin
      C supplementation in pregnant women. Interventions using a multivitamin
      supplement containing vitamin C or where the primary supplement was iron were
      excluded. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials
      for inclusion, extracted data and assessed trial quality. MAIN RESULTS: Five
      trials, involving 766 women, are included in this review. No difference was seen
      between women supplemented with vitamin C alone or combined with other
      supplements compared with placebo for the risk of stillbirth (relative risk (RR)
      0.87, 95% confidence intervals (CI) 0.41 to 1.87, three trials, 539 women),
      perinatal death (RR 1.16, 95% CI 0.61 to 2.18, two trials, 238 women),
      birthweight (weighted mean difference (WMD) -139.00 g, 95% CI -517.68 to 239.68,
      one trial, 100 women) or intrauterine growth restriction (RR 0.72, 95% CI 0.49 to
      1.04, two trials, 383 women). Women supplemented with vitamin C alone or combined
      with other supplements were at increased risk of giving birth preterm (RR 1.38,
      95% CI 1.04 to 1.82, three trials, 583 women). Significant heterogeneity was
      found for neonatal death and pre-eclampsia. No difference was seen between women
      supplemented with vitamin C combined with other supplements for the risk of
      neonatal death (RR 1.73, 95% CI 0.25 to 12.12, two trials, 221 women), using a
      random-effects model. For pre-eclampsia, women supplemented with vitamin C
      combined with other supplements were at decreased risk when using a fixed-effect
      model (RR 0.47, 95% CI 0.30 to 0.75, four trials, 710 women); however, this
      difference could not be demonstrated when using a random-effects model (RR 0.52,
      95% CI 0.23 to 1.20, four trials, 710 women). AUTHORS' CONCLUSIONS: The data are
      too few to say if vitamin C supplementation, alone or combined with other
      supplements, is beneficial during pregnancy. Preterm birth may have been
      increased with vitamin C supplementation.

PMID- 15846697
TI  - Vitamin supplementation for preventing miscarriage.
AB  - BACKGROUND: Miscarriage is a common complication of pregnancy that can be caused
      by a wide range of factors. Poor dietary intake of vitamins has been associated
      with an increased risk of miscarriage, therefore supplementing women with
      vitamins either prior to or in early pregnancy may help prevent miscarriage.
      OBJECTIVES: The objectives of this review are to determine the effectiveness and
      safety of any vitamin supplementation, on the risk of spontaneous miscarriage,
      maternal adverse outcomes and fetal and infant adverse outcomes. SEARCH STRATEGY:
      We searched the Cochrane Pregnancy and Childbirth Group Trials Register (8
      September 2004), the Cochrane Central Register of Controlled Trials (The Cochrane
      Library, Issue 2, 2003) and MEDLINE (1966 to May 2003), Current Contents (1998 to
      May 2003) and EMBASE (1980 to May 2003). SELECTION CRITERIA: All randomised and
      quasi-randomised trials comparing one or more vitamins with either placebo, other
      vitamins, no vitamins or other interventions, prior to conception,
      periconceptionally or in early pregnancy (less than 20 weeks' gestation). DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trials for
      inclusion, extracted data and assessed trial quality. MAIN RESULTS: We identified
      seventeen trials assessing supplementation with any vitamin(s) starting prior to
      20 weeks' gestation and reporting at least one primary outcome that were eligible
      for the review. Overall, the included trials involved 35,812 women and 37,353
      pregnancies. Two trials were cluster randomised and contributed data for 20,758
      women and 22,299 pregnancies in total. No difference was seen between women
      taking any vitamins compared with controls for total fetal loss (relative risk
      (RR) 1.05, 95% confidence interval (CI) 0.95 to 1.15), early or late miscarriage
      (RR 1.08, 95% CI 0.95 to 1.24) or stillbirth (RR 0.85, 95% CI 0.63 to 1.14) and
      most of the other primary outcomes, using fixed-effect models. For the other
      primary outcomes, women given any type of vitamin(s) compared with controls were
      less likely to develop pre-eclampsia (RR 0.68, 95% CI 0.54 to 0.85, four trials,
      5580 women) and more likely to have a multiple pregnancy (RR 1.38, 95% CI 1.12 to
      1.70, three trials, 20,986 women). AUTHORS' CONCLUSIONS: Taking vitamin
      supplements, alone or in combination with other vitamins, prior to pregnancy or
      in early pregnancy, does not prevent women experiencing miscarriage or
      stillbirth. However, women taking vitamin supplements may be less likely to
      develop pre-eclampsia and more likely to have a multiple pregnancy.

PMID- 15846698
TI  - Long-term non-pharmacologic weight loss interventions for adults with type 2
      diabetes.
AB  - BACKGROUND: Most persons with type 2 diabetes are overweight and obesity worsens
      the metabolic and physiologic abnormalities associated with diabetes. OBJECTIVES:
      The objective of this review is to assess the effectiveness of lifestyle and
      behavioral weight loss and weight control interventions for adults with type 2
      diabetes. SEARCH STRATEGY: Studies were obtained from computerized searches of
      multiple electronic bibliographic databases, supplemented with hand searches of
      selected journals and consultation with experts in obesity research. The last
      search was conducted May, 2004. SELECTION CRITERIA: Studies were included if they
      were published or unpublished randomized controlled trials in any language, and
      examined weight loss or weight control strategies using one or more dietary,
      physical activity, or behavioral interventions, with a follow-up interval of at
      least 12 months. DATA COLLECTION AND ANALYSIS: Effects were combined using a
      random effects model. MAIN RESULTS: The 22 studies of weight loss interventions
      identified had a 4,659 participants and follow-up of 1 to 5 years. The pooled
      weight loss for any intervention in comparison to usual care among 585 subjects
      was 1.7 kg (95 % confidence interval [CI] 0.3 to 3.2), or 3.1% of baseline body
      weight among 517 subjects. Other main comparisons demonstrated nonsignificant
      results: among 126 persons receiving a physical activity and behavioral
      intervention, those who also received a very low calorie diet lost 3.0 kg (95% CI
      -0.5 to 6.4), or 1.6% of baseline body weight, more than persons receiving a low
      calorie diet. Among 53 persons receiving identical dietary and behavioral
      interventions, those receiving more intense physical activity interventions lost
      3.9 kg (95% CI -1.9 to 9.7), or 3.6% of baseline body weight, more than those
      receiving a less intense or no physical activity intervention. Comparison groups
      often achieved significant weight loss (up to 10.0 kg), minimizing between-group
      differences. Changes in glycated hemoglobin generally corresponded to changes in
      weight and were not significant when between-group differences were examined. No
      data were identified on quality of life and mortality. AUTHORS' CONCLUSIONS:
      Weight loss strategies using dietary, physical activity, or behavioral
      interventions produced small between-group improvements in weight. These results
      were minimized by weight loss in the comparison group, however, and examination
      of individual study arms revealed that multicomponent interventions including
      very low calorie diets or low calorie diets may hold promise for achieving weight
      loss in adults with type 2 diabetes.

PMID- 15846699
TI  - Nonsteroidal anti-inflammatory drugs (NSAIDs) versus opioids for acute renal
      colic.
AB  - BACKGROUND: Renal colic is a common cause of acute severe pain. Both opioids and
      nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended for treatment, but
      the relative efficacy of these drugs is uncertain. OBJECTIVES: To examine the
      benefits and disadvantages of NSAIDs and opioids for the management of pain in
      acute renal colic. SEARCH STRATEGY: We searched the Cochrane Renal Group's
      specialised register (May 2003), the Cochrane Central Register of Randomised
      Controlled Trials (CENTRAL - The Cochrane Library issue 2, 2003), MEDLINE (1966 -
      31 January 2003), EMBASE (1980 - 31 January 2003) and handsearched reference
      lists of retrieved articles. Most recent search date: January 2005 SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing any opioid with any
      NSAID, regardless of dose or route of administration were included. DATA
      COLLECTION AND ANALYSIS: Data was extracted and quality assessed independently by
      two reviewers, with differences resolved by discussion. Dichotomous outcomes are
      reported as relative risk (RR) and measurements on continuous scales are reported
      as weighted mean differences (WMD) with 95% confidence intervals. Subgroup
      analysis by study quality, drug type and drug route have been performed where
      possible to explore reasons for heterogeneity. MAIN RESULTS: Twenty trials from
      nine countries with a total of 1613 participants were identified. Both NSAIDs and
      opioids lead to clinically significant falls in patient-reported pain scores. Due
      to unexplained heterogeneity these results could not be pooled although 10/13
      studies reported lower pain scores in patients receiving NSAIDs. Patients treated
      with NSAIDs were significantly less likely to require rescue medication (RR 0.75,
      95% CI 0.61 to 0.93, P = 0.007), though most of these trials used pethidine. The
      majority of trials showed a higher incidence of adverse events in patients
      treated with opioids, but there was significant heterogeneity between studies so
      the results could not be pooled. There was significantly less vomiting in
      patients treated with NSAIDs (RR 0.35, 95% CI 0.23 to 0.53, P < 0.00001). In
      particular, patients receiving pethidine had a much higher rate of vomiting
      compared with patients receiving NSAIDs. Gastrointestinal bleeding and renal
      impairment were not reported. AUTHORS' CONCLUSIONS: Both NSAIDs and opioids can
      provide effective analgesia in acute renal colic. Opioids are associated with a
      higher incidence of adverse events, particularly vomiting. Given the high rate of
      vomiting associated with the use of opioids, particularly pethidine, and the
      greater likelihood of requiring further analgesia, we recommend that if an opioid
      is to be used it should not be pethidine.

PMID- 15846700
TI  - Treatment for methaqualone dependence in adults.
AB  - BACKGROUND: Methaqualone is a potent quinazoline, a class of sedative-hypnotics,
      that has a high potential for abuse. While the oral use of methaqualone
      (Quaalude, Mandrax) has waned in western countries since the mid-late 1980's, the
      practice of smoking methaqualone is a serious public health problem in South
      Africa, other parts of Africa and India. In the context of diminishing resources
      devoted to substance abuse treatment in regions affected by methaqualone abuse,
      it would be desirable to base treatment on the best evidence available. This
      review aimed to provide health care workers, policy-makers and consumers with the
      necessary information to make decisions regarding effective treatment of this
      highly dependence-producing drug. OBJECTIVES: To compare the effectiveness of any
      type of pharmacological or behavioural treatment administered in either an in
      patient or out-patient setting compared with either a placebo or no treatment or
      a waiting list, or with another form of treatment administered in either an in-
      or out-patient setting. SEARCH STRATEGY: The authors searched the following
      databases: Cochrane Drugs and Alcohol Group'Register of Trials (February 2004);
      Cochrane Central Register of Controlled Trials (CENTRAL-The Cochrane Library,
      Issue 2, 2004); MEDLINE (OVID - January 1966 to february 2004), PsycInfo (OVID -
      January 1967 to february 2004). Relevant conference proceedings and reference
      lists of relevant articles were hand-searched. Broad internet searches were
      conducted and contact made with experts in the field. SELECTION CRITERIA: All
      randomised controlled trials and quasi-randomised trials of the effectiveness of
      treatment programmes (in- or out-patient) for methaqualone dependence and abuse
      were considered for inclusion in this review. DATA COLLECTION AND ANALYSIS: The
      authors independently assessed study eligibility and quality. MAIN RESULTS: No
      studies were found that met the inclusion criteria. AUTHORS' CONCLUSIONS: To
      date, no randomized controlled trials appear to have been conducted.
      Consequently, the effectiveness of inpatient versus outpatient treatment,
      psychosocial treatment versus no treatment, and pharmacological treatments versus
      placebo for methaqualone abuse or dependence has yet to be established.

PMID- 15846701
TI  - Clinical decision support systems for neonatal care.
AB  - BACKGROUND: Clinical decision support systems (CDSS) are computer-based
      information systems used to integrate clinical and patient information to provide
      support for decision-making in patient care. They may be useful in aiding the
      diagnostic process, the generation of alerts and reminders, therapy
      critiquing/planning, information retrieval, and image recognition and
      interpretation. CDSS for use in adult patients have been evaluated using
      randomised control trials and their results analysed in systematic reviews. There
      is as yet no systematic review on CDSS use in neonatal medicine. OBJECTIVES: To
      examine whether the use of clinical decision support systems has an effect on 1.
      the mortality and morbidity of newborn infants and 2. the performance of
      physicians treating them SEARCH STRATEGY: The standard search method of the
      Cochrane Neonatal Review Group was used. Searches were made of the Cochrane
      Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1,
      2004), MEDLINE (from 1966 to August 2004), EMBASE (1980-2004), CINAHL (1982 to
      August 2004) and AMED (1985 to August 2004). SELECTION CRITERIA: Randomised or
      quasi-randomised controlled trials which compared the effects of CDSS versus no
      CDSS in the care of newborn infants. Trials which compared CDSS against other
      CDSS were also considered. The eligible interventions were CDSS for computerised
      physician order entry, computerised physiological monitoring, diagnostic systems
      and prognostic systems. DATA COLLECTION AND ANALYSIS: Studies were assessed for
      eligibility using a standard pro forma. Methodological quality was assessed
      independently by the different investigators. MAIN RESULTS: Two studies fitting
      the selection criteria were found for computer aided prescribing and one study
      for computer aided physiological monitoring.Computer-aided prescribing: one study
      (Cade 1997) examined the effects of computerised prescribing of parenteral
      nutrition ordering. No significant effects on short-term outcomes were found and
      longer term outcomes were not studied. The second study (Balaguer 2001)
      investigated the effects of a database program in aiding the calculation of
      neonatal drug dosages. It was found that the time taken for calculation was
      significantly reduced and there was a significant reduction in the number of
      calculation errors.Computer-aided physiological monitoring: one eligible study
      (Cunningham 1998) was found which examined the effects of computerised cot side
      physiological trend monitoring and display. There were no significant effects on
      mortality, volume of colloid infused, frequency of blood gases sampling (samples
      per day) or severe (Papile Grade 4) intraventricular haemorrhage. Published data
      did not permit us to analyse effects on long-term neurodevelopmental outcome.
      AUTHORS' CONCLUSIONS: There are very limited data from randomised trials on which
      to assess the effects of clinical decision support systems in neonatal care.
      Further evaluation of CDSS using randomised controlled trials is warranted.

PMID- 15846702
TI  - Topically applied anaesthetics for treating perineal pain after childbirth.
AB  - BACKGROUND: Perineal trauma is a major problem affecting millions of women around
      the world each year. The degree of perineal pain and discomfort associated with
      perineal trauma is often underestimated. Pain often interferes with basic daily
      activities for the woman such as walking, sitting and passing urine and also
      negatively impacts on motherhood experiences. OBJECTIVES: To assess the effects
      of topically applied anaesthetics for relief of perineal pain following
      childbirth whilst in hospital and following discharge. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group Trials Register (February
      2004), CINAHL (1982 to December 2002) and MIDIRS (last searched February 2003).
      We checked reference lists of trials and review articles. SELECTION CRITERIA:
      Randomised controlled trials comparing topically applied anaesthetic with no
      treatment, placebo or alternative treatment. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed trial eligibility and quality and double-entered
      the data. We contacted study authors for additional information. MAIN RESULTS:
      Eight trials made up of 976 women were included in the review. Five of these
      trials measured pain experienced up to 24 hours after birth but different methods
      to assess pain were used in each of the studies. All five trials showed no
      difference in pain relief when the topical anaesthetic was compared with placebo.
      One of these studies looked at topical anaesthetics compared with indomethacin
      vaginal suppositories but there was no significant difference in mean pain
      scores. All trials reported only short-term follow up (up to four days). Two
      trials looked at additional analgesia taken for perineal pain, with one trial
      finding that less additional analgesia was required with epifoam use in
      comparison with placebo (relative risk (RR) 0.58, 95% confidence interval (CI)
      0.40 to 0.84, one trial, 97 women). However, lignocaine/lidocaine showed no
      difference with regard to additional analgesia use. Adverse effects were not
      formally measured in the studies; however, some studies commented that there were
      no side-effects severe enough to discontinue treatment. One study found that the
      women in the treatment group were more satisfied than the placebo group (RR 0.09,
      95% CI 0.01 to 0.65, one trial, 103 women). AUTHORS' CONCLUSIONS: Evidence for
      the effectiveness of topically applied local anaesthetics for treating perineal
      pain is not compelling. There has been no evaluation for the long-term effects of
      topically applied local anaesthetics.

PMID- 15846703
TI  - Electrotherapy for neck disorders.
AB  - BACKGROUND: Neck disorders are common, disabling and costly. The effectiveness of
      electrotherapy as a physiotherapy option has remained unclear. OBJECTIVES: To
      assess whether electrotherapy, either alone or in combination with other
      treatments, relieves pain, or improves function/disability, patient satisfaction,
      and global perceived effect in adults with mechanical neck disorders (MND).
      SEARCH STRATEGY: Computer-assisted searches of bibliographic databases: CENTRAL,
      MEDLINE, EMBASE, MANTIS, CINAHL, and ICL, without language restrictions, from
      their beginning to March 2003. SELECTION CRITERIA: Randomised or controlled
      clinical trials with quasi-randomisation (alternate allocation, case record
      numbers, dates of birth, etc.), in any language, investigating the effects of
      electrotherapy as a treatment for MND. DATA COLLECTION AND ANALYSIS: At least two
      authors independently conducted citation identification, study selection, data
      abstraction, and methodological quality assessment. Using a random-effects model,
      relative risk, and standardized mean differences were calculated. The
      reasonableness of combining studies was assessed on clinical and statistical
      grounds. Due to heterogeneity, pooled effect measures were not calculated. MAIN
      RESULTS: Fourteen comparisons (525 people with MND), in 11 publications, were
      included in this review. The analysis was limited by underpowered low quality
      trials, paucity of literature, and heterogeneity of treatment subtypes. The
      results for the electrotherapy subtypes are: Limited evidence of benefit: low or
      high frequency pulsed electromagnetic field (PEMF) compared to placebo, provides
      immediate post treatment pain relief only for chronic MND, acute whiplash (WAD)
      Unclear or conflicting evidence: direct and modulated Galvanic current compared
      to other treatments for pain in acute, subacute, chronic occipital headache
      iontophoresis compared to other treatments for pain, RTW, and self-assessment of
      overall outcome in acute, subacute WAD TENS compared to placebo for pain in acute
      WAD, chronic MND PEMF compared to placebo for medium or long term effect on pain,
      patient assessment of improvement, ADL in acute WAD, chronic MND Limited evidence
      of no benefit: diadynamic current compared to placebo for reduction of trigger
      point tenderness in chronic MND with radicular findings, cervicogenic headache
      permanent magnets compared to a placebo for pain in chronic MND electric muscle
      stimulation compared to a sham control for pain in chronic MND. AUTHORS'
      CONCLUSIONS: We can not make any definitive statements on electrotherapy for MND.
      The current evidence on Galvanic current (direct or pulsed), iontophoresis, TENS,
      EMS, PEMF and permanent magnets is either lacking, limited, or conflicting.
      Possible new trials on these interventions should have larger patient samples and
      include more precise standardization and description of all treatment
      characteristics.

PMID- 15846704
TI  - Vitamins for epilepsy.
AB  - BACKGROUND: Vitamins have been reported to be effective in controlling certain
      types of seizures and to prevent some of the harmful effects of antiepileptic
      drugs (AEDs). In this review we will summarize evidence from randomized
      controlled trials. OBJECTIVES: To assess if vitamins improve seizure control,
      reduce adverse effects of AEDs or improve the quality of life in people with
      epilepsy. SEARCH STRATEGY: We searched MEDLINE from 1966 to 2004, the Cochrane
      Epilepsy Group trials register (December 2004), CENTRAL (the Cochrane Controlled
      Trials Register) (TheCochraneLibrary Issue 4, 2004), and cross-references from
      identified studies. SELECTION CRITERIA: Randomized or quasi-randomized studies
      investigating the effects of one or more vitamins given alone or in addition to
      AEDs to people of any age with any type of epilepsy. DATA COLLECTION AND
      ANALYSIS: Both reviewers assessed the trials for inclusion and extracted the
      data. Outcomes assessed included seizure frequency, gingival hyperplasia,
      neuropathy, changes in bone mineral content, serum calcium, alkaline phosphatase,
      hemogram, serum levels of AEDs, neuropsychological and quality of life outcomes.
      Primary analyses were by intention to treat. MAIN RESULTS: Fifteen studies met
      our inclusion criteria and were of poor methodological quality. None described
      randomization methods and most enrolled small numbers of participants. Nine
      studies (331 participants) investigated folic acid. Two studies (75 participants)
      found no effect for the outcome 50% or greater reduction in seizure frequency (OR
      0.96; 95% CI 0.32 to 2.29). Also, no evidence was found for an effect on gingival
      health, intelligence, behavior, mental health or personality, or measures of red
      blood volume and hemoglobin content. Folic acid was not associated with any
      consistent changes in serum phenytoin or phenobarbitone levels or improvement in
      the mean motor conduction velocities of peripheral nerves. One small study (72
      participants) found that thiamine improves neuropsychological functions related
      to psychomotor speed, visuospatial abilities, selective attention and verbal
      abstracting ability. One study (226 participants) found a significantly higher
      bone mineral content (BMC) among patients with epilepsy taking AEDs with vitamin
      D supplementation compared to controls who were not given supplementation (OR
      3.6; 95% CI 2.48 to 4.72; p < 0.00001). The studies found no significant effects
      on serum calcium, alkaline phosphatase or general well-being. One small study (24
      participants) found a significant decrease in seizure frequency in those treated
      with vitamin E compared to placebo (p = 0.00005; Peto OR 26.73; 95% CI 5.46 to
      130.92). AUTHORS' CONCLUSIONS: In view of methodological deficiencies and limited
      number of individual studies, we have found no reliable evidence to support the
      routine use of vitamins in patients with epilepsy. Further trials are needed,
      especially to assess the utility of vitamin D supplementation to prevent
      osteomalacia and the role of vitamin E on seizures and thiamine in improving
      cognitive functions.

PMID- 15846705
TI  - Competitions and incentives for smoking cessation.
AB  - BACKGROUND: Material or financial incentives may be used in an attempt to
      reinforce behaviour change, including smoking cessation. They have been widely
      used in workplace smoking cessation programmes, and to a lesser extent within
      community programmes. Quit and Win contests are the subject of a companion
      review. OBJECTIVES: To determine whether competitions and incentives lead to
      higher long-term quit rates. We also set out to examine the relationship between
      incentives and participation rates. SEARCH STRATEGY: We searched the Cochrane
      Tobacco Addiction Group Specialized Register, with additional searches of MEDLINE
      (January 1966 to September 2004), EMBASE (1980 to 2004/8), CINAHL (1982 to
      2004/8) and PsycINFO (1872 to 2004/6). Search terms included incentive*,
      competition*, contest*, reward*, prize*, contingent payment*, deposit contract*.
      SELECTION CRITERIA: We considered randomized controlled trials, allocating
      individuals, workplaces, groups within workplaces, or communities to experimental
      or control conditions. We also considered controlled studies with baseline and
      post-intervention measures. DATA COLLECTION AND ANALYSIS: Data were extracted by
      one author and checked by the second. We contacted study authors for additional
      data where necessary. The main outcome measure was abstinence from smoking for at
      least six months from the start of the intervention. We used the most rigorous
      definition of abstinence in each trial, and biochemically validated rates where
      available. Where possible we performed meta-analysis using a generic inverse
      variance model, grouped by timed endpoints, but not pooled across the subgroups.
      MAIN RESULTS: Fifteen studies met our inclusion criteria. None of the studies
      demonstrated significantly higher quit rates for the incentives group than for
      the control group beyond the six-month assessment. There was no clear evidence
      that participants who committed their own money to the programme did better than
      those who did not, or that different types of incentives were more or less
      effective. There is some evidence that although cessation rates have not been
      shown to differ significantly, recruitment rates can be improved by rewarding
      participation, which may be expected to deliver higher absolute numbers of
      successful quitters. Cost effectiveness analysis is not appropriate to this
      review, since the efficacy of the intervention has not been demonstrated.
      AUTHORS' CONCLUSIONS: Incentives and competitions do not appear to enhance long
      term cessation rates, with early success tending to dissipate when the rewards
      are no longer offered. Rewarding participation and compliance in contests and
      cessation programmes may have more potential to deliver higher absolute numbers
      of quitters.

PMID- 15846706
TI  - Megestrol acetate for the treatment of anorexia-cachexia syndrome.
AB  - BACKGROUND: Megestrol acetate (MA) is currently used to improve appetite and to
      increase weight in cancer-associated anorexia. In 1993 MA was approved by the
      USA's Federal Drug Administration for the treatment of anorexia, cachexia, or
      unexplained weight loss in patients with AIDS. The mechanism by which MA
      increases appetite is unknown, and its effectiveness for anorexia and cachexia in
      neoplastic and AIDS patients is under investigation. OBJECTIVES: To evaluate the
      efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome
      in patients with cancer, AIDS and other underlying pathologies. SEARCH STRATEGY:
      Studies were sought thorough an extensive search of the electronic databases,
      journals, reference lists, contact with investigators and other search strategies
      outlined in the methods. The most recent search was carried out on October 2002.
      SELECTION CRITERIA: Studies were included in the review if they assessed
      megestrol acetate compared to placebo or other drug treatments in randomized
      controlled trials of patients with a clinical diagnosis of anorexia-cachexia
      related to cancer, AIDS or another underlying pathology. DATA COLLECTION AND
      ANALYSIS: Data extraction was conducted by two independent authors, and
      methodological quality evaluated. Quantitative analyses were performed using
      appetite and quality of life as a dichotomous variable, and weight gain was
      analysed as continuous and dichotomous variables. Studies with more than 50% of
      patients lost to follow-up were excluded from the analysis. MAIN RESULTS: Thirty
      trials met the inclusion criteria (4123 patients). Twenty-one trials compared MA
      at different doses with placebo; four compared different doses of MA versus other
      drugs; two compared MA with other drugs and placebo; and three compared different
      doses of MA. For all patient conditions, meta-analysis showed a benefit of MA
      compared with placebo, particularly with regard to appetite improvement and
      weight gain in cancer patients. Analysing quality of life, clinical and
      statistical heterogeneity was found and discussed. There was insufficient
      information to define the optimal dose of MA. AUTHORS' CONCLUSIONS: This review
      demonstrates that MA improves appetite and weight gain in patients with cancer.
      No overall conclusion about quality of life (QOL) could be drawn due to
      heterogeneity. The small number of patients, methodological shortcomings and poor
      reporting have not allowed us to recommend megestrol acetate in AIDS patients or
      with other underlying pathologies.

PMID- 15846707
TI  - Quality of life after rectal resection for cancer, with or without permanent
      colostomy.
AB  - BACKGROUND: For almost one hundred years abdominoperineal excision has been the
      standard treatment of choice for rectal cancer. With advances in the techniques
      for rectal resection and anastomosis, anterior resection with preservation of the
      sphincter function has become the preferred treatment for rectal cancers, except
      for those cancers very close to the anal sphincter. The main reason for this has
      been the conviction that the quality of life for patients with a colostomy after
      abdominoperineal excision was poorer than for patients undergoing a sphincter
      preserving technique. However, patients having sphincter-preserving operations
      may experience symptoms affecting their quality of life that are different from
      those with stoma-patients. OBJECTIVES: To compare the quality of life in rectal
      cancer patients with or without permanent colostomy. SEARCH STRATEGY: We searched
      PUBMED, EMBASE, LILACS, the Cochrane Central Register of Controlled Trials
      (CENTRAL), the Cochrane Colorectal Cancer Group's specialised register. Abstract
      books from major gastroenterological and colorectal congresses were searched.
      Reference lists of the selected articles were scrutinized. SELECTION CRITERIA:
      All controlled clinical trials and observational studies in which quality of life
      was measured in patients with rectal cancer having either abdominoperineal
      excision or low anterior resection, using a validated quality of life instrument,
      were considered. DATA COLLECTION AND ANALYSIS: One reviewer (JP) checked the
      titles and abstracts identified from the databases and hand search. Full text
      copies of all studies of possible relevance were obtained. The reviewer decided
      which studies met the inclusion criteria. Both reviewers independently extracted
      data. If information was insufficient the original author was contacted to obtain
      missing data. Extracted data were crosschecked and discrepancies resolved by
      consensus. MAIN RESULTS: Thirty potential studies were identified. Eleven of
      these, all non-randomised and representing 1412 participants met the inclusion
      criteria. Six trials found that people undergoing abdominoperineal excision did
      not have poorer quality of life measures than patients undergoing anterior
      resection. One study found that a stoma only slightly affected the person's
      quality of life. Four studies found that patients receiving abdominoperineal
      excision had significantly poorer quality of life than after anterior resection.
      Due to heterogeneity, meta-analysis of the included studies was not possible.
      AUTHORS' CONCLUSIONS: The studies included in this review do not allow firm
      conclusions as to the question of whether the quality of life of people after
      anterior resection is superior to that of people after abdominoperineal excision.
      The included studies challenged the assumption that anterior resection patients
      fare better.Larger, better designed and executed prospective studies are needed
      to answer this question.

PMID- 15846708
TI  - Bioresorbable fixation devices for musculoskeletal injuries in adults.
AB  - BACKGROUND: Bioresorbable implants for musculoskeletal injuries involving bone
      and ligaments in adults might have significant advantages compared to the
      conventionally used non-resorbable metal implants because they lead to a gradual
      transfer of the mechanical load from the implant to the healing bone and do not
      require a secondary removal operation. Tissue reactions may present a problem and
      bioresorbable screws are mechanically not as strong as their metal counterparts.
      OBJECTIVES: To compare bioresorbable implants to non-resorbable implants with
      respect to functional outcome, wound infections, other complications and
      reoperation rate,in the fixation of bone fractures or re-attachment of soft
      tissue to bone. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal
      Injuries Group Specialised Register (March 2004), the Cochrane Central Register
      of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE (1966 to
      February 2004), EMBASE (1988 to February 2004), BL Inside (to February 2004),
      SIGLE (to February 2004), the metaRegister of Controlled Trials at
      http//:controlled-trials.com/, and reference lists of articles. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised trials,
      comparing bioresorbable osteosynthesis with metal osteosynthesis (including
      titanium and stainless steel implants) were included. DATA COLLECTION AND
      ANALYSIS: Review authors independently assessed trial quality and extracted data.
      Data were pooled where relevant and possible. Sub-analyses for specific type of
      fractures and for specific type of tissue reactions were performed. Requests for
      more information were sent to trialists. MAIN RESULTS: No significant difference
      between the bioresorbable and other implants could be demonstrated with respect
      to functional outcome, infections and other complications. Reoperation rates were
      lower in some of the groups of people treated with bioresorbable implants.
      AUTHORS' CONCLUSIONS: In a selected group of compliant patients with simple
      fractures, the use of bioresorbable fixation devices might be advantageous.

PMID- 15846709
TI  - Recall intervals for oral health in primary care patients.
AB  - BACKGROUND: The frequency with which patients should attend for a dental check-up
      and the potential effects on oral health of altering recall intervals between
      check-ups have been the subject of ongoing international debate for almost 3
      decades. Although recommendations regarding optimal recall intervals vary between
      countries and dental healthcare systems, 6-monthly dental check-ups have
      traditionally been advocated by general dental practitioners in many developed
      countries. OBJECTIVES: To determine the beneficial and harmful effects of
      different fixed recall intervals (for example 6 months versus 12 months) for the
      following different types of dental check-up: a) clinical examination only; b)
      clinical examination plus scale and polish; c) clinical examination plus
      preventive advice; d) clinical examination plus preventive advice plus scale and
      polish. To determine the relative beneficial and harmful effects between any of
      these different types of dental check-up at the same fixed recall interval. To
      compare the beneficial and harmful effects of recall intervals based on
      clinicians' assessment of patients' disease risk with fixed recall intervals. To
      compare the beneficial and harmful effects of no recall interval/patient driven
      attendance (which may be symptomatic) with fixed recall intervals. SEARCH
      STRATEGY: We searched the Cochrane Oral Health Group Trials Register, the
      Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE.
      Reference lists from relevant articles were scanned and the authors of some
      papers were contacted to identify further trials and obtain additional
      information. Date of most recent searches: 9th April 2003. SELECTION CRITERIA:
      Trials were selected if they met the following criteria: design- random
      allocation of participants; participants - all children and adults receiving
      dental check-ups in primary care settings, irrespective of their level of risk
      for oral disease; interventions -recall intervals for the following different
      types of dental check-ups: a) clinical examination only; b) clinical examination
      plus scale and polish; c) clinical examination plus preventive advice; d)
      clinical examination plus scale and polish plus preventive advice; e) no recall
      interval/patient driven attendance (which may be symptomatic); f) clinician risk
      based recall intervals; outcomes - clinical status outcomes for dental caries
      (including, but not limited to, mean dmft/DMFT, dmfs/DMFS scores, caries
      increment, filled teeth (including replacement restorations), early carious
      lesions arrested or reversed); periodontal disease (including, but not limited
      to, plaque, calculus, gingivitis, periodontitis, change in probing depth,
      attachment level); oral mucosa (presence or absence of mucosal lesions,
      potentially malignant lesions, cancerous lesions, size and stage of cancerous
      lesions at diagnosis). In addition the following outcomes were considered where
      reported: patient-centred outcomes, economic cost outcomes, other outcomes such
      as improvements in oral health knowledge and attitudes, harms, changes in dietary
      habits and any other oral health-related behavioural change. DATA COLLECTION AND
      ANALYSIS: Information regarding methods, participants, interventions, outcome
      measures and results were independently extracted, in duplicate, by two authors.
      Authors were contacted, where deemed necessary and where possible, for further
      details regarding study design and for data clarification. A quality assessment
      of the included trial was carried out. The Cochrane Oral Health Group's
      statistical guidelines were followed. MAIN RESULTS: Only one study (with 188
      participants) was included in this review and was assessed as having a high risk
      of bias. This study provided limited data for dental caries outcomes (dmfs/DMFS
      increment) and economic cost outcomes (reported time taken to provide
      examinations and treatment). AUTHORS' CONCLUSIONS: There is insufficient evidence
      from randomised controlled trials (RCTs) to draw any conclusions regarding the
      potential beneficial and harmful effects of altering the recall interval between
      dental check-ups. There is insufficient evidence to support or refute the
      practice of encouraging patients to attend for dental check-ups at 6-monthly
      intervals. It is important that high quality RCTs are conducted for the outcomes
      listed in this review in order to address the objectives of this review.

PMID- 15846710
TI  - Short term ambulatory oxygen for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Ambulatory oxygen is defined as the use of supplemental oxygen during
      exercise and activities of daily living. Ambulatory oxygen therapy is often used
      for patients on long term oxygen therapy during exercise, or for non long term
      oxygen therapy users who achieve some subjective and/or objective benefit from
      oxygen during exercise. The evidence for the use of ambulatory oxygen therapy is
      extrapolated from two sources: longer term studies and single assessment studies.
      Longer term studies assess the impact of ambulatory oxygen therapy used at home
      during activities of daily living. Single assessment studies compare performance
      during an exercise test using oxygen with performance during an exercise test
      using placebo air. OBJECTIVES: To determine the efficacy of ambulatory oxygen in
      patients with COPD using single assessment studies. SEARCH STRATEGY: The Cochrane
      Airways Group COPD register was searched with predefined search terms. Searches
      were current as of March 2004. SELECTION CRITERIA: Only randomised controlled
      trials were included. Studies did not have to be blinded. Studies had to compare
      oxygen and placebo when administered to people with COPD who were undergoing an
      exercise test. DATA COLLECTION AND ANALYSIS: Two reviewers (JB, B'ON) extracted
      and entered data in to RevMan 4.2.7. MAIN RESULTS: Twenty-seven studies
      (contributing 29 data sets), randomising 469 participants met the inclusion
      criteria of the review. Oxygen improved all pooled outcomes relating to endurance
      exercise capacity (distance, time, number of steps) and maximal exercise capacity
      (exercise time and work rate). Data relating to VO2max could not be pooled and
      results from the original studies were not consistent. For the secondary outcomes
      of breathlessness, SaO2 and VE, comparisons were made at isotime. In all studies
      except two the isotime is defined as the time at which the placebo test ended.
      Oxygen improved breathlessness, SaO2/PaO2 and VE at isotime with endurance
      exercise testing. There was no data on breathlessness at isotime with maximal
      exercise testing. Oxygen improved SaO2/PaO2 at isotime; the reduction in VE did
      not reach statistical significance. AUTHORS' CONCLUSIONS: This review provides
      some evidence from small, single assessment studies that ambulatory oxygen
      improves exercise performance in people with moderate to severe COPD. The results
      of the review may be affected by publication bias, and the small sample sizes in
      the studies. Although positive, the findings of the review require replication in
      larger trials with more distinct subgroups of participants. Maximal or endurance
      tests can be used in ambulatory oxygen assessment, but endurance tests may be
      more appropriate as they are more related to activities of daily living.
      Consideration should be given to the measurement of SaO2 and breathlessness at
      isotime as these provide important additional information. We recommend that
      these outcomes are included in the assessment for ambulatory oxygen. Future
      research needs to establish the level of benefit of ambulatory oxygen in specific
      subgroups of people with COPD.

PMID- 15846711
TI  - Antidepressant prevention of postnatal depression.
AB  - BACKGROUND: Postnatal depression is a common and important complication of
      childbearing. Untreated depression can lead to potentially negative effects on
      the foetus and infant, in addition to serious morbidity for the mother. The use
      of antidepressants during pregnancy for prevention of postnatal depression is
      unclear, due to the possibility of adverse effects on the mother and developing
      foetus, and the difficulty of reliably identifying the women who would go on to
      develop postnatal depression. OBJECTIVES: To evaluate the effectiveness of
      different antidepressant drugs in addition to standard clinical care in the
      prevention of postnatal depression. To compare the effectiveness of different
      antidepressant drugs and with any other form of intervention for postnatal
      depression i.e. hormonal, psychological or social support. To assess any adverse
      effects of antidepressant drugs in either the mother or the foetus/infant. SEARCH
      STRATEGY: The register of clinical trials maintained and updated by the Cochrane
      Depression, Anxiety and Neurosis Group and the Cochrane Pregnancy and Childbirth
      Group. SELECTION CRITERIA: Randomised studies of antidepressants alone or in
      combination with another treatment, compared with placebo or a psychosocial
      intervention in non-depressed pregnant women or women who had given birth in the
      previous six weeks (i.e. women at risk of postnatal depression) DATA COLLECTION
      AND ANALYSIS: Data were extracted independently from the trial reports by the
      authors. Missing information was requested from investigators wherever possible.
      Data were sought to allow an "intention to treat" analysis. MAIN RESULTS: Two
      trials fulfilled the inclusion criteria for this review. Both looked at women
      with a past history of postpartum depression. Nortriptyline (n=26) (Wisner 2001)
      did not show any benefit over placebo (n=25). Sertraline (n=14) Wisner 2004
      reduced the recurrence of postnatal depression and the time to recurrence when
      compared with placebo (n=8). Intention to treat analyses were not carried out in
      either trial. AUTHORS' CONCLUSIONS: It is not possible to draw any clear
      conclusions about the effectiveness of antidepressants given immediately
      postpartum in preventing postnatal depression and, therefore, cannot be
      recommended for prophylaxis of postnatal depression, due to the lack of clear
      evidence. Larger trials are needed which also include comparisons of
      antidepressant drugs with other prophylactic treatments to reflect clinical
      practice, and examine adverse effects for the foetus and infant, as well as
      assess womens' attitudes to the use of antidepressants at this time.

PMID- 15846712
TI  - Medical versus surgical interventions for open angle glaucoma.
AB  - BACKGROUND: Open angle glaucoma (OAG) is the commonest cause of irreversible
      blindness worldwide. OBJECTIVES: To study the relative effects of medical and
      surgical treatment of OAG. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966
      to February 2005), EMBASE (1988 to February 2005), and reference lists of
      articles. We also contacted researchers in the field. SELECTION CRITERIA:
      Randomised controlled trials comparing medications to surgery in adults. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and
      extracted data. We contacted trial investigators for missing information. MAIN
      RESULTS: Four trials involving 888 participants with previously untreated OAG
      were included. Surgery was Scheie's procedure in one trial and trabeculectomy in
      three trials. In three trials, primary medication was usually pilocarpine, in one
      trial a beta-blocker. In the most recent trial, participants with mild OAG,
      progressive visual field (VF) loss, after adjustment for cataract surgery, was
      not significantly different for medications compared to trabeculectomy (Odds
      ratio (OR) 0.74; 95% CI 0.54 to 1.01). Reduction of vision, with a higher risk of
      developing cataract (OR 2.69, 95%% CI 1.64 to 4.42), and more patient discomfort
      was more likely with trabeculectomy than medication. There is some evidence, from
      three trials, for people with moderately advanced glaucoma that medication is
      associated with more progressive VF loss and 6 to 8 mmHg less intraocular
      pressure (IOP) lowering than surgery, either by a Scheie's procedure or
      trabeculectomy. There was a trend towards an increased risk of failed IOP control
      over time for initial pilocarpine treatment compared to trabeculectomy. In the
      longer-term (two trials) the risk of failure was significantly greater with
      medication than trabeculectomy (OR 3.90, 95% CI 1.60 to 9.53; HR 7.27, 95% CI
      2.23 to 25.71). Medicine and surgery have evolved since these trials were
      undertaken, and additionally the evidence is potentially subject to detection and
      attrition bias. AUTHORS' CONCLUSIONS: Evidence from one trial suggests, for mild
      OAG, that VF deterioration up to five-years is not significantly different
      whether treatment is initiated with medication or trabeculectomy. Reduced vision,
      cataract and eye discomfort are more likely with trabeculectomy. There is some
      evidence, for more severe OAG, that initial medication (pilocarpine, now rarely
      used as first line medication) is associated with greater VF deterioration than
      surgery. In general, surgery lowers IOP more than medication. There was no
      evidence to determine the effectiveness of contemporary medication (prostaglandin
      analogues, alpha2-agonists and topical carbonic anhydrase inhibitors) compared to
      surgery in severe OAG, and in people of black African ethnic origin who have a
      greater risk of more severe open angle glaucoma. More research is required.

PMID- 15846713
TI  - Empiric antibiotic coverage of atypical pathogens for community acquired
      pneumonia in hospitalized adults.
AB  - BACKGROUND: Community acquired pneumonia (CAP) is caused by various pathogens,
      traditionally divided to 'typical' and 'atypical'. Initial antibiotic treatment
      of CAP is usually empirical, customarily covering both typical and atypical
      pathogens. To date, no sufficient evidence exists to support this broad coverage,
      while limiting coverage is bound to reduce toxicity, resistance and expense.
      OBJECTIVES: Assess the efficacy and need of adding antibiotic coverage for
      atypical pathogens in hospitalized patients with CAP, in terms of mortality and
      successful treatment. SEARCH STRATEGY: We searched the Cochrane Central Register
      of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005) which
      includes the Acute Respiratory Infection Group's specialized register; MEDLINE
      (January 1966 to January Week 2 2005); and EMBASE (January 1980 to January Week 2
      2005). SELECTION CRITERIA: Randomized trials of adult patients hospitalized due
      to CAP, comparing antibiotic regimens with atypical antibiotic coverage to a
      regimen without atypical antibiotic coverage. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently appraised the quality of each trial and extracted the
      data from included trials. Relative risks (RR) with 95% confidence intervals (CI)
      were estimated, assuming an intention-to-treat (ITT) basis for the outcome
      measures. MAIN RESULTS: Twenty four trials were included, encompassing 5015
      randomized patients. There was no difference in mortality between the atypical
      arm and the non-atypical arm (RR 1.13; 95% CI 0.82 to 1.54). The atypical arm
      showed an insignificant trend toward clinical success and a significant advantage
      to bacteriological eradication, which disappeared when evaluating
      methodologically high-quality studies alone. Clinical success for the atypical
      arm was significantly higher for Legionella pneumophilae (L. pneumophilae) and
      non-significantly lower for pneumococcal pneumonia. There was no significant
      difference between the groups in the frequency of (total) adverse events, or
      those requiring discontinuation of treatment. However, gastrointestinal events
      were more common in the non-atypical arm (RR 0.73, 95% CI 0.54 to 0.99). AUTHORS'
      CONCLUSIONS: No benefit of survival or clinical efficacy was shown to empirical
      atypical coverage in hospitalized patients with CAP. This conclusion relates
      mostly to the comparison of quinolone monotherapy to non-atypical monotherapy.
      Further trials, comparing beta-lactam (BL) or cephalosporin therapy to BL or
      cephalosporin combined with a macrolide in this population, using mortality as
      its primary outcome, should be performed.

PMID- 15846714
TI  - Intravenous immunoglobulin for multifocal motor neuropathy.
AB  - BACKGROUND: Multifocal motor neuropathy is a rare, probably immune mediated
      disorder characterised by slowly progressive, asymmetric, distal weakness of one
      or more limbs with no objective loss of sensation. It may cause prolonged periods
      of disability. The treatment options for multifocal motor neuropathy are sparse.
      Patients with multifocal motor neuropathy do not usually respond to steroids or
      plasma exchange, and may even worsen with these treatments. Many uncontrolled
      studies have suggested a beneficial effect of intravenous immunoglobulin.
      OBJECTIVES: To review systematically the evidence from randomised controlled
      trials concerning the efficacy and safety of intravenous immunoglobulin in
      multifocal motor neuropathy. SEARCH STRATEGY: We used the search strategy of the
      Cochrane Neuromuscular Disease Review Group to search the Disease Group register
      (searched September 2003), MEDLINE (January 1990 to September 2003), EMBASE
      (January 1990 to September 2003) and ISI (January 1990 to September 2003)
      databases for randomised controlled trials. SELECTION CRITERIA: Randomised
      controlled studies examining the effects of any dose of intravenous
      immunoglobulin versus placebo in patients with definite or probable multifocal
      motor neuropathy. Outcome measures had to include one of the following:
      disability, strength, or conduction block. Studies which reported the frequency
      of adverse effects were used to assess safety. DATA COLLECTION AND ANALYSIS: Two
      authors reviewed literature searches to identify potentially relevant trials,
      scored their quality and extracted data independently. For dichotomous data, we
      calculated relative risks, and for continuous data, effect sizes and weighted
      pooled effect sizes. Statistical uncertainty was expressed with 95% confidence
      intervals. MAIN RESULTS: Four randomised controlled trials including a total of
      34 patients were suitable for this systematic review. Strength improved in 78% of
      patients treated with intravenous immunoglobulin and only 4% of placebo-treated
      patients. Disability improved in 39% of patients after intravenous immunoglobulin
      treatment and in 11% after placebo (statistically not significantly different).
      Mild, transient side effects were reported in 71% of intravenous immunoglobulin
      treated patients. Serious side effects were not encountered. AUTHORS'
      CONCLUSIONS: Limited evidence from randomised controlled trials shows that
      intravenous immunoglobulin has a beneficial effect on strength. There was a non
      significant trend towards improvement in disability. More research is needed to
      discover whether intravenous immunoglobulin improves disability and is cost
      effective.

PMID- 15846715
TI  - Gangliosides for acute spinal cord injury.
AB  - BACKGROUND: Spinal cord injury (SCI) results in loss of feeling and movement. The
      consequences can be devastating for the patient and his or her carers. Global
      estimates of the number of new cases annually range from 15 to 40 per million.
      Leading causes of acute SCI are road traffic injury, violence, and injuries
      sustained in sports and other recreational activities. Care for people with SCI
      has improved, leading to an increase in survival rates. Attempts to improve
      patients' feeling and movement have involved the use of a wide range of
      treatments. Gangliosides are compounds that occur naturally in cell membranes.
      Laboratory studies have suggested they may have protective effects on nerves and
      even help them to re-grow. Clinical trials have taken place using gangliosides
      (usually GM1 ganglioside) for a number of neurological conditions. OBJECTIVES: To
      quantify the evidence for the effectiveness and safety of gangliosides when used
      to treat acute SCI. SEARCH STRATEGY: We searched the following databases to
      identify trials for inclusion: CENTRAL, MEDLINE, EMBASE, and the National
      Research Register. We also searched web-based trials registers, such as Current
      Controlled Trials. We approached the manufacturers of the most widely used
      ganglioside and researchers in this field to try to locate any unpublished data.
      SELECTION CRITERIA: Randomised controlled trials of any ganglioside versus
      controls, in patients with SCI. Outcome measures specified were: mortality,
      recovery of motor function, improvement in sensory measures, measures of
      functional activity, infections and any other adverse events. DATA COLLECTION AND
      ANALYSIS: Data were extracted from published studies and authors were contacted
      for further information. All data found was dichotomous and odds ratios (with 95%
      CIs) were calculated. A fixed-effects model was assumed. MAIN RESULTS: Two
      studies met the inclusion criteria. There were no deaths in one (n=37). In the
      other (n=760), there were slightly more deaths in the treatment group than in the
      control group; odds ratio 1.07 (0.57, 2.00 95%CI) - a result that can be
      explained by the play of chance. Methodological weaknesses regarding the
      collection and presentation of data from the two studies made it impossible to
      reach any conclusions regarding the effect of gangliosides on the other specified
      outcomes. AUTHORS' CONCLUSIONS: The evidence available does not support the use
      of ganglioside treatment to reduce the death rate in SCI patients. No evidence
      has yet emerged that ganglioside treatment improves recovery or quality of life
      in survivors.

PMID- 15846716
TI  - The 'WHO Safe Communities' model for the prevention of injury in whole
      populations.
AB  - BACKGROUND: The safe communities approach has been embraced around the world as a
      model for coordinating community efforts to enhance safety and reduce injury.
      Over 80 communities throughout the world have been formally designated as 'Safe
      Communities' by the World Health Organization. It is of public health interest to
      determine to what degree the model is successful, and whether its application
      does indeed reduce injury rates in communities to which it is introduced.
      OBJECTIVES: To determine the effectiveness of the Safe Communities model to
      prevent injury in whole populations, or targeted sub-groups of populations.
      SEARCH STRATEGY: The search strategy was based on electronic searches,
      handsearches of selected journals, snowballing from reference lists of selected
      publications and contacting a key person from each WHO-designated Safe Community.
      SELECTION CRITERIA: Studies were independently screened for inclusion by two
      reviewers. Included studies were those conducted within a WHO Safe Community that
      reported changes in population injury rates within the community compared to a
      control community. DATA COLLECTION AND ANALYSIS: Data were independently
      extracted by two reviewers. Meta-analysis was not appropriate, due to the
      heterogeneity of the included studies. MAIN RESULTS: Only seven WHO Safe
      Communities, of more than 80 worldwide, have undertaken controlled evaluations
      using objective sources of injury data. These communities represent only four
      countries from two geographical regions in the world: the Scandinavian countries
      of Sweden and Norway and the Pacific nations of Australia and New Zealand. Safe
      Communities in Sweden and Norway have resulted in significant reductions in
      injury rates. The Australian and New Zealand communities have been unable to
      replicate the same level of success. AUTHORS' CONCLUSIONS: Evidence suggests the
      WHO Safe Communities model is effective in reducing injuries in whole
      populations. However, important methodological limitations exist in all studies
      from which evidence can be obtained. A lack of reported detail makes it unclear
      which factors facilitate or hinder a programme's success, and makes uncertain,
      whether the success of any particular application of the model is necessarily
      replicable in other communities. In evaluated programmes that did not report
      significant decreases in injury rates, this lack of information makes it
      difficult to distinguish between evidence of no effect of the model, or no
      evidence of effect. The four countries that have evaluated their Safe Communities
      with a sufficiently rigorous study design have higher economic wealth and health
      standards and lower injury rates than much of the world. No evaluations were
      available from other parts of the world, despite the designation of WHO Safe
      Communities in countries such as South Africa, Bangladesh, China, Vietnam,
      Canada, UK and USA. Generalisation of results of studies conducted in just four
      countries, to the international population needs to be done with caution. There
      is a need for more high-quality, methodologically strong evaluations of the model
      in a range of diverse communities and detailed reporting of implementation
      processes.

PMID- 15846717
TI  - Emergency ultrasound-based algorithms for diagnosing blunt abdominal trauma.
AB  - BACKGROUND: Ultrasonography is regarded as the tool of choice for early
      diagnostic investigations in patients with suspected blunt abdominal trauma.
      Although its sensitivity is too low for definite exclusion of abdominal organ
      injury, proponents of ultrasound argue that ultrasound-based clinical pathways
      enhance the speed of primary trauma assessment, reduce the number of computed
      tomography scans and cut costs. OBJECTIVES: To assess the efficiency and
      effectiveness of trauma algorithms that include ultrasound examinations in
      patients with suspected blunt abdominal trauma. SEARCH STRATEGY: We searched
      MEDLINE, EMBASE, CENTRAL, CCMED, publishers' databases, controlled trials
      registers and the Internet. Bibliographies of identified articles and congress
      abstracts were handsearched. Trials were obtained from the Cochrane Injuries
      Group's trials register. Authors were contacted for further information and
      individual patient data. SELECTION CRITERIA:  PARTICIPANTS: patients with blunt
      torso, abdominal or multiple trauma undergoing diagnostic investigations for
      abdominal organ injury. INTERVENTIONS: diagnostic algorithms comprising emergency
      ultrasonography (US). CONTROLS: diagnostic algorithms without US ultrasound
      examinations (e.g. primary computed tomography [CT] or diagnostic peritoneal
      lavage [DPL]). OUTCOME MEASURES: mortality, use of CT and DPL, cost
      effectiveness, laparotomy and negative laparotomy rates, delayed diagnoses, and
      quality of life. STUDIES: randomised controlled trials (RCTs) and quasi
      randomised trials (qRCTs). DATA COLLECTION AND ANALYSIS: Two reviewers
      independently selected trials for inclusion, assessed methodological quality and
      extracted data. Where possible, data were pooled and relative risks (RRs), risk
      differences (RDs) and weighted mean differences, each with 95% confidence
      intervals (CIs), were calculated by fixed- or random-effects modelling, as
      appropriate. MAIN RESULTS: We identified two RCTs with US in the experimental arm
      and another with US in the control group. We also considered two qRCTs. Overall,
      trials were of moderate methodological quality. Few authors responded to our
      written inquiries seeking to resolve controversial issues and to obtain
      individual patient data. We were able to pool data from two trials comprising
      1037 patients for primary endpoint analysis (i.e. mortality). The relative risk
      in favour of the no-US arm was 1.4 (95% CI 0.94 to 2.08). Because of a lack of
      details, the meaning of this observation remains unclear. There was a marginal
      benefit with US-based pathways in reducing CT scans (random-effects RD -0.46; 95%
      CI -1.00 to 0.13), offset by trials of higher methodological rigour. No
      differences were observed in DPL and laparotomy rates. AUTHORS' CONCLUSIONS:
      There is insufficient evidence from RCTs to justify promotion of ultrasound-based
      clinical pathways in diagnosing patients with suspected blunt abdominal trauma.

PMID- 15846718
TI  - Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever).
AB  - BACKGROUND: Fluoroquinolones are recommended as first-line therapy for typhoid
      and paratyphoid fever, but how they compare with other cheaper antibiotics and
      different fluoroquinolones is unclear. OBJECTIVES: To evaluate fluoroquinolone
      antibiotics for treating enteric fever in children and adults compared with other
      antibiotics, different fluoroquinolones, and different treatment durations of the
      same fluoroquinolone. SEARCH STRATEGY: We searched the Cochrane Infectious
      Diseases Group Specialized Register (August 2004), CENTRAL (The Cochrane Library
      Issue 3, 2004), MEDLINE (1966 to August 2004), EMBASE (1974 to August 2004),
      LILACS (1982 to August 2004), conference proceedings, reference lists, and
      contacted researchers. SELECTION CRITERIA: Randomized controlled trials of
      fluoroquinolones in people with blood or bone marrow culture-confirmed enteric
      fever. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the
      methodological quality of trials and extracted data. We calculated the odds ratio
      (OR) for dichotomous data with 95% confidence intervals. We analysed norfloxacin
      separately. MAIN RESULTS: Thirty-three trials met the inclusion criteria; 22 had
      unclear allocation concealment, and 29 were not blinded. Three trials exclusively
      included children, and two studied outpatients. The main analysis examined
      clinical failure, microbiological failure, and relapse. Compared with
      chloramphenicol, fluoroquinolones were not statistically significantly different
      for clinical (544 participants) or microbiological failure (378 participants) in
      adults; they reduced clinically diagnosed relapse in adults (OR 0.14, 0.04 to
      0.50; 467 participants, 6 trials), but this was not statistically significant in
      participants with blood culture-confirmed relapse (121 participants, 2 trials).
      Compared with co-trimoxazole, we detected no statistically significant difference
      (82 participants, 2 trials). Among adults, fluoroquinolones reduced clinical
      failure compared with ceftriaxone (OR 0.08, 0.01 to 0.45; 120 participants, 3
      trials), but showed no difference for microbiological failure or relapse. We
      detected no statistically significant difference between fluoroquinolones and
      cefixime (80 participants, 1 trial) or azithromycin (152 participants, 2 trials).
      In trials of hospitalized children, fluoroquinolones were not statistically
      significantly different from ceftriaxone (60 participants, 1 trial, involving
      norfloxacin) or cefixime (82 participants, 1 trial). Norfloxacin had more
      clinical failures than other fluoroquinolones (417 participants, 5 trials).
      Trials comparing different durations of fluoroquinolone treatment showed no
      statistically significant differences (693 participants, 8 trials). AUTHORS'
      CONCLUSIONS: Many trials were small, and methodological quality varied widely.
      Although enteric fever most commonly affects children, trials in this group were
      particularly sparse. Insufficient data in all comparisons preclude any firm
      conclusions to be made regarding superiority of fluoroquinolones over first-line
      antibiotics in children and adults.

PMID- 15846719
TI  - Antibiotic regimens for secondary peritonitis of gastrointestinal origin in
      adults.
AB  - BACKGROUND: Secondary peritonitis is associated with a high mortality rate and if
      not treated successfully leads to development of abscesses, severe sepsis and
      multi-organ failure. Source control and adjunctive antibiotics are the mainstay
      of treatment. However, no conclusive evidence suggest that one antibiotic regimen
      is better than any other but at the same time have a lower toxicity. OBJECTIVES:
      To ascertain the efficacy and adverse effects of different antibiotic regimens in
      treating intra-abdominal infections in adults. Outcomes were divided into primary
      (clinical success and effectiveness in reducing mortality) and secondary
      (microbiological success, preventing wound infection, intra-abdominal abscess,
      clinical sepsis, remote infection, superinfection, adverse reactions, duration of
      treatment required, effectiveness in reducing hospitalised stay, and time to
      defervescence). SEARCH STRATEGY: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (Cochrane Library, Issue 4, 2004), MEDLINE (from 1966
      to November 2004), EMBASE (from 1980 to November 2004) and Cochrane Colorectal
      Cancer Group specialised register SR-COLOCA. Bibliographies of identified studies
      were screened for further relevant trials. SELECTION CRITERIA: Randomised and
      quasi-randomised controlled trials comparing different antibiotic regimens in the
      treatment of secondary peritonitis in adults were selected. Trials reporting
      gynaecological or traumatic peritonitis were excluded from this review. Ambiguity
      regarding suitability of trials were discussed among the review team. DATA
      COLLECTION AND ANALYSIS: Six reviewers independently assessed trial quality and
      extracted data. Data collection was standardised using data collection form to
      ensure uniformity among reviewers. Statistical analyses were performed using the
      random effects model and the results expressed as odds ratio for dichotomous
      outcomes, or weight mean difference for continuous data with 95% confidence
      intervals. MAIN RESULTS: Fourty studies with 5094 patients met the inclusion
      criteria. Sixteen different comparative antibiotic regimens were reported. All
      antibiotics showed equivocal comparability in terms of clinical success.
      Mortality did not differ between the regimens. Despite the potential high
      toxicity profile of regimens using aminoglycosides, this was not demonstrated in
      this review. The reason for this could be the inherent bias within clinical
      trials in the form of patient selection and stringency in monitoring drug levels.
      AUTHORS' CONCLUSIONS: No specific recommendations can be made for the first line
      treatment of secondary peritonitis in adults with antibiotics, as all regimens
      showed equivocal efficacy. Other factors such as local guidelines and
      preferences, ease of administration, costs and availability must therefore be
      taken into consideration in deciding the antibiotic regimen of choice. Future
      trials should attempt to stratify patients and perform intention-to-treat
      analysis to allow better external validity.

PMID- 15846720
TI  - Physical measures for treating depression in dialysis patients.
AB  - BACKGROUND: Depression is the most common psychological problem in the chronic
      dialysis population. The diagnosis of depression in patients on chronic dialysis
      is confounded by the fact that several symptoms of uraemia mimic the somatic
      components of depression. It affects their physical, psychological and social
      well-being. Furthermore, the frequent occurrence of cardiovascular problems and
      the pharmacokinetic consequences of renal impairment may make drug treatment of
      depression difficult. OBJECTIVES: The aim of this systematic review was to assess
      the efficacy and safety of physical measures in the treatment of depression in
      patients who are dialysed for end-stage renal disease. SEARCH STRATEGY: A
      comprehensive search strategy was employed to identify all Randomised Controlled
      Trials (RCTs) relevant to the treatment of depression in patients on chronic
      dialysis. The following database were searched - MEDLINE (1966-March 2004),
      EMBASE (1980-March 2004), PSYCHINFO (1872-March 2004), The Cochrane Library
      (Issue 1, 2004). Authors of included studies were contacted, reference lists of
      identified RCTs and relevant narrative reviews were screened. SELECTION CRITERIA:
      RCTs comparing drugs with placebo or no treatment, or a comparison of drugs
      against a combination of electroconvulsive therapy and drugs. DATA COLLECTION AND
      ANALYSIS: Data were abstracted by two investigators independently onto a standard
      form and subsequently entered into Review Manager 4.2. Relative risk (RR) for
      dichotomous data and a (weighted) mean difference (WMD) for continuous data were
      calculated with 95% confidence intervals (95% CI). MAIN RESULTS: Only one trial,
      with a total of 12 patients and of eight weeks duration was identified. The trial
      compared fluoxetine against placebo in depressed patients on chronic dialysis.
      This study did not show any significant difference in depression scores between
      the treatment and control groups or safety. AUTHORS' CONCLUSIONS: Firm
      conclusions on the efficacy of physical methods of treatment cannot be made as we
      identified only one small RCT that was of short duration. More larger and longer
      term RCTs are needed in this area. Current screening tools for depression are
      recognised to have poor specificity in the medically ill due to overlap of
      somatic symptoms of the medical illness. The development of a valid diagnostic
      tool would be helpful.

PMID- 15846721
TI  - Inpatient versus other settings for detoxification for opioid dependence.
AB  - BACKGROUND: There are a complex range of variables that can influence the course
      and subjective severity of opioid withdrawal. There is a growing evidence for the
      effectiveness of a range of medically-supported detoxification strategies, but
      little attention has been paid to the influence of the setting in which the
      process takes place. OBJECTIVES: To evaluate the effectiveness of any inpatient
      opioid detoxification programme when compared with all other time-limited
      detoxification programmes on the level of completion of detoxification, the
      intensity and duration of withdrawal symptoms, the nature and incidence of
      adverse effects, the level of engagement in further treatment post
      detoxification, and the rates of relapse post-detoxification. SEARCH STRATEGY:
      Electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL
      - The Cochrane Library Issue 3, 2004); MEDLINE (January 1966-March 2004); EMBASE
      (January 1988-March 2004); PsycInfo (January 1967-March 2004); CINAHL (January
      1982-March 2004). In addition the Current Contents, Biological Abstracts, Science
      Citation Index and Social Sciences Index were searched. SELECTION CRITERIA:
      Randomised controlled clinical trials comparing inpatient opioid detoxification
      (any drug or psychosocial therapy) with other time-limited detoxification
      programmes (including residential units that are not staffed 24 hours per day,
      day-care facilities where the patient is not resident for 24 hours per day, and
      outpatient or ambulatory programmes, and using any drug or psychosocial therapy).
      DATA COLLECTION AND ANALYSIS: All abstracts were independently inspected by two
      reviewers (ED & JI) and relevant papers were retrieved and assessed for
      methodological quality using Cochrane Reviewers' Handbook criteria. MAIN RESULTS:
      Only one study met the inclusion criteria. This did not explicitly report the
      number of participants in each group that successfully completed the
      detoxification process, but the published data allowed us to deduce that 7 out of
      10 (70%) in the inpatient detoxification group were opioid-free on discharge,
      compared with 11 out of 30 (37%) in the outpatient group. There was very limited
      data about the other outcomes of interest. AUTHORS' CONCLUSIONS: This review
      demonstrates that there is no good available research to guide the clinician
      about the outcomes or cost-effectiveness of inpatient or outpatient approaches to
      opioid detoxification.

PMID- 15846722
TI  - Lactase treated feeds to promote growth and feeding tolerance in preterm infants.
AB  - BACKGROUND: Successful transition from parenteral nutrition to full enteral
      feedings during the immediate neonatal period is associated with improved growth
      in preterm infants. Lactase is the last of the major intestinal disaccharidases
      to develop in preterm infants. Because of inadequate lactase activity, preterm
      infants are unable to digest lactose. Lactase preparations could potentially be
      used to hydrolyze lactose in formulas and breast milk to minimize lactose
      malabsorption in preterm infants. OBJECTIVES: To assess the effectiveness and
      safety of the addition of lactase to milk compared to placebo or no intervention
      for the promotion of growth and feeding tolerance in preterm infants. PRIMARY
      OUTCOMES: Weight gain expressed as g/kg/day, growth expressed as weight, length
      and head circumference percentile for gestational age, assessed at birth and at
      40 weeks post-menstrual age, days to achieve full enteral feeds. SECONDARY
      OUTCOMES: Several common outcomes associated with preterm birth, and adverse
      effects. SEARCH STRATEGY: Electronic and manual searches were conducted in
      January 2005 of Cochrane Central Register of Controlled Trials (CENTRAL, The
      Cochrane Library, Issue 4, 2004), MEDLINE (1966-Jan 2005), EMBASE (1980-Jan 2005)
      and CINAHL (1982-Jan 2005), personal files, bibliographies of identified trials
      and abstracts by the Pediatric Academic Societies' and the European Society of
      Pediatric Research Meetings published in Pediatric Research. SELECTION CRITERIA:
      Types of studies: Randomized or quasi-randomized controlled trials. PARTICIPANTS:
      Preterm infants < 37 weeks gestational age. INTERVENTION: Addition of lactase to
      milk versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: The
      standard methods of the Cochrane Neonatal Review Group were followed
      independently by the reviewers to assess study quality and report outcomes.
      Treatment effects, calculated using RevMan 4.2, included relative risk (RR), risk
      difference (RD) and mean difference (MD), all with 95% confidence intervals (CI).
      A fixed effect model was used for meta-analyses. Heterogeneity tests were not
      performed as only one study was identified. MAIN RESULTS: One study enrolling 130
      infants of 26 - 34 weeks postconceptual age (mean postnatal age at entry 11 days)
      was identified and no identified study was excluded. The study was a double blind
      randomized controlled trial of high quality. Lactase treated feeds were initiated
      when enteral feedings provided > 75% of daily intake. None of the primary
      outcomes outlined in the protocol for this review and only one of the secondary
      outcomes, necrotizing enterocolitis (NEC), were reported on. The RR for NEC was
      0.32 (95% CI 0.32 (0.01, 7.79); the RD was -0.02 (95% CI -0.06, 0.03) (a
      reduction which was not statistically significant). There was a statistically
      significant increase in weight gain at study day 10 in the lactase treated feeds
      group but not at any other time points. Overall, there ws not a statistically
      significant effect on weight gain. No adverse effects were noted. AUTHORS'
      CONCLUSIONS: The only randomized trial to date provides no evidence of
      significant benefit to preterm infants from adding lactase to their feeds.
      Further research regarding effectiveness and safety are required before practice
      recommendations can be made. Randomized controlled trials comparing lactase vs
      placebo treated feeds and enrolling infants when enteral feeds are introduced are
      recommended. The primary and secondary outcomes for effectiveness and safety
      should include those identified in this review.

PMID- 15846723
TI  - Unit-dose packaged drugs for treating malaria.
AB  - BACKGROUND: Unit-dose packaging of antimalarial drugs may improve malaria cure by
      making it easier for patients to take their treatment correctly. OBJECTIVES: To
      summarize the effects of unit-dose packaged treatment on cure and treatment
      adherence in people with uncomplicated malaria. SEARCH STRATEGY: We searched the
      Cochrane Infectious Diseases Group Specialized Register (November 2004), CENTRAL
      (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to November 2004), EMBASE
      (1980 to November 2004), LILACS (November 2004), conference proceedings, and
      reference lists of articles. We also contacted pharmaceutical companies,
      organizations, and researchers in the field. SELECTION CRITERIA: Randomized
      controlled trials (RCTs), cluster-RCTs, quasi-RCTs, and controlled before-and
      after studies of unit-dose packaged drugs for treating uncomplicated malaria.
      DATA COLLECTION AND ANALYSIS: We independently assessed study eligibility and
      methodological quality, and extracted data for an intention to treat analysis,
      where possible. We combined binary data using relative risk (RR) and the fixed
      effect model, and presented them with 95% confidence intervals (CI). We attempted
      to contact study authors for additional information. MAIN RESULTS: Three quasi
      RCTs (895 participants) and one cluster-RCT (6 health facilities) met the
      inclusion criteria. Trials were of poor methodological quality, and none
      adequately assessed treatment failure. Unit-dose packaged drugs (in conjunction
      with prescriber training and patient information) appeared to be associated with
      higher participant-reported treatment adherence in all trials.A meta-analysis of
      two trials (596 participants) showed that participant-reported treatment
      adherence was higher with blister-packed tablets compared with tablets in paper
      envelopes (RR 1.18, 1.12 to 1.25). Two trials using tablets in sectioned
      polythene bags as the intervention also noted an increase in participant-reported
      treatment adherence: the cluster-RCT (6 clusters) compared it with tablets in
      paper envelopes, and the other trial compared it with syrup in bottles (RR 2.15,
      1.76 to 2.61; 299 participants). AUTHORS' CONCLUSIONS: There is insufficient
      evidence to determine the effect of unit-dose packaged antimalarial drugs on
      treatment failure. Unit-dose packaging supported by prescriber training and
      patient information appears to improve participant-reported treatment adherence,
      but these data come from trials with methodological limitations.

PMID- 15846724
TI  - Hyperbaric oxygen as an adjuvant treatment for malignant otitis externa.
AB  - BACKGROUND: Malignant, or necrotising, otitis externa is a potentially fatal
      infection of the external ear canal and surrounding soft tissue and bone. It may
      be complicated by involvement of cranial nerves, principally the facial nerves
      and the contents of the jugular foramen. It is an uncommon condition mainly found
      in the elderly or in diabetics. OBJECTIVES: To assess the effectiveness of
      adjunctive hyperbaric oxygen treatment for malignant otitis externa. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library Issue 4, 2003), MEDLINE (January 1966 to April
      2004) and EMBASE (January 1985 to April 2004) with pre-specified terms. The date
      of the last search was 5th April 2004. SELECTION CRITERIA: Randomised controlled
      trials, involving adults, undergoing hyperbaric oxygen therapy in malignant
      otitis externa. DATA COLLECTION AND ANALYSIS: No identified articles described
      randomised controlled trials of hyperbaric oxygen therapy in the treatment of
      malignant otitis externa. MAIN RESULTS: Due to the lack of data no results could
      be presented. AUTHORS' CONCLUSIONS: No clear evidence exists to demonstrate the
      efficacy of hyperbaric oxygen therapy when compared to treatment with antibiotics
      and/or surgery. No data were found to compare rates of complication between the
      different treatment modalities. Further research is required.

PMID- 15846725
TI  - Vibroacoustic stimulation for fetal assessment in labour in the presence of a
      nonreassuring fetal heart rate trace.
AB  - BACKGROUND: Fetal vibroacoustic stimulation is a simple, non-invasive technique
      where a device is placed on the maternal abdomen over the region of the fetal
      head and sound is emitted at a predetermined level for several seconds. It is
      hypothesized that the resultant startle reflex in the fetus and subsequent fetal
      heart rate acceleration or transient tachycardia following vibroacoustic
      stimulation provide reassurance of fetal well-being. This technique has been
      proposed as a tool to assess fetal well-being in the presence of a non-reassuring
      cardiotocographic trace during the first and second stages of labour. OBJECTIVES:
      To evaluate the clinical effectiveness and safety of vibroacoustic stimulation in
      the assessment of fetal well-being during labour, compared with mock or no
      stimulation for women with a singleton pregnancy exhibiting a non-reassuring
      fetal heart rate pattern. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group Trials Register (30 September 2004), the Cochrane Central
      Register of Controlled Trials (The Cochrane Library, Issue 1, 2004), MEDLINE
      (January 1966 to January 2005), EMBASE (January 1966 to January 2005) and
      reference lists of all retrieved articles. We sought unpublished trials and
      abstracts submitted to major international congresses and contacted expert
      informants. SELECTION CRITERIA: All published and unpublished randomised trials
      that compared maternal and fetal/neonatal/infant outcomes when vibroacoustic
      stimulation was used to evaluate fetal status in the presence of a non-reassuring
      cardiotocographic trace during labour, compared with mock or no stimulation. DATA
      COLLECTION AND ANALYSIS: Two independent review authors identified potential
      studies from the literature search and assessed them for methodological quality
      and appropriateness of inclusion, using a data extraction form. Attempts to
      contact study authors for additional information were unsuccessful. MAIN RESULTS:
      The search strategies yielded six studies for consideration of inclusion.
      However, none of these studies fulfilled the requirements for inclusion in this
      review. AUTHORS' CONCLUSIONS: There are currently no randomised controlled trials
      that address the safety and efficacy of vibroacoustic stimulation used to assess
      fetal well-being in labour in the presence of a non-reassuring cardiotocographic
      trace. Although vibroacoustic stimulation has been proposed as a simple, non
      invasive tool for assessment of fetal well-being, there is insufficient evidence
      from randomised trials on which to base recommendations for use of vibroacoustic
      stimulation in the evaluation of fetal well-being in labour in the presence of a
      non-reassuring cardiotocographic trace.

PMID- 15846726
TI  - Duration of antibacterial treatment for uncomplicated urinary tract infection in
      women.
AB  - BACKGROUND: Uncomplicated urinary tract infection (UTI) is a common disease,
      occurring frequently in young sexually active women. In the past, seven day
      antibiotic therapy was recommended while the current practice is to treat
      uncomplicated UTI for three days. OBJECTIVES: TO compare the efficacy and safety
      of three-day antibiotic therapy to multi-day therapy (five days or longer) on
      relief of symptoms and bacteriuria at short-term and long-term follow-up. SEARCH
      STRATEGY: The Cochrane Library (Issue 1, 2004), the Cochrane Renal Group's
      Register of trials (July 2003), EMBASE (January 1980 to August 2003), and MEDLINE
      (January 1966 to August 2003) were searched. We scanned references of all
      included studies and contacted the first or corresponding author of included
      trials and the pharmaceutical companies. SELECTION CRITERIA: Randomised
      controlled trials comparing three-days oral antibiotic therapy with multi-day
      therapy (five days and longer) for uncomplicated cystitis in 18 to 65 years old
      non-pregnant women without signs of upper UTI. DATA COLLECTION AND ANALYSIS: Data
      concerning bacteriological and symptomatic failure rates, occurrence of
      pyelonephritis and adverse effects were extracted independently by two reviewers.
      Relative risk (RR) and their 95% confidence intervals (CI) were estimated.
      Outcomes were also extracted by intention-to-treat analysis whenever possible.
      MAIN RESULTS: Thirty-two trials (9605 patients) were included. For symptomatic
      failure rates, no difference between three-day and 5-10 day antibiotic regimen
      was seen short-term (RR 1.06, 95% CI 0.88 to 1.28) and long-term follow-up (RR
      1.09, 95% CI 0.94 to 1.27). Comparison of the bacteriological failure rates
      showed that three-day therapy was less effective than 5-10 day therapy for the
      short-term follow-up, however this difference was observed only in the subgroup
      of trials that used the same antibiotic in the two treatment arms (RR 1.37, 95%
      CI 1.07 to 1.74, P = 0.01). This difference was more significant at long-term
      follow-up (RR 1.43, 95% CI 1.19 to 1.73, P = 0.0002). Adverse effects were
      significantly more common in the 5-10 day treatment group (RR 0.83, 95% CI 0.74
      to 0.93, P = 0.0010). Results were consistent for subgroup and sensitivity
      analyses. AUTHORS' CONCLUSIONS: Three days of antibiotic therapy is similar to 5
      10 days in achieving symptomatic cure during uncomplicated UTI treatment, while
      the longer treatment is more effective in obtaining bacteriological cure. In
      spite of the higher rate of adverse effects, treatment for 5-10 days could be
      considered for treatment of women in whom eradication of bacteriuria is
      important.

PMID- 15846727
TI  - Paraprofessionals for anxiety and depressive disorders.
AB  - BACKGROUND: The established mental health care system does not have the resources
      to meet the extensive need for care of those with anxiety and depressive
      disorders. Paraprofessionals partially replacing professionals may be cost
      effective. OBJECTIVES: To investigate the effectiveness of any kind of
      psychological treatment for anxiety and depressive disorders performed by
      paraprofessionals compared with professionals, waiting list or placebo condition.
      To examine whether the results apply to clinically significant anxiety and
      depressive disorders of referred patients with a psychiatric history and/or whose
      illness has lasted two years or more. SEARCH STRATEGY: CCDANCTR-Studies using the
      following terms: (paraprofessional* or para-professional* or non-professional* or
      non-professional* or peer or volunt*); EMBASE (ExerptaMedica), MEDLINE and
      PsycINFO, all years published, key words: para-/paraprofessional, non
      /nonprofessional, rand*, respectively psy*; citation lists of articles reviewing
      the subject and included studies; correspondence with authors of controlled
      studies and review reports on the subject. SELECTION CRITERIA: Randomised
      controlled trials that used symptom measures, and compared the effects of
      psychological treatments given by paraprofessionals (mental health care workers,
      paid or voluntary, unqualified with respect to the psychological treatment) with
      psychological treatments given by professionals, and with waiting list or placebo
      condition. DATA COLLECTION AND ANALYSIS: The standard mean difference was used to
      pool continuous data from each trial, and odds ratios were used to pool
      dichotomous data, using a random effects model. The generic inverse variance
      method was used for combining continuous and dichotomous data. The effect of low
      quality studies and the use of self-rated versus observer-rated measures were
      tested, and subgroup analyses were performed for differences between depression
      and anxiety diagnosis, paraprofessionals with/without professional background,
      group/individual intervention, length of follow-up and gender (post-hoc subgroup
      analysis). MAIN RESULTS: Five studies, all using self-report measures, reported
      five comparisons of paraprofessionals versus professionals (n=106) and five
      comparisons of paraprofessionals versus control condition (n=220). No differences
      were found between paraprofessionals and professionals (SMD=0.09, 95% CI -0.23 to
      0.40, p=0.58; no significant heterogeneity). Studies comparing paraprofessionals
      versus control reported mixed continuous and dichotomous data showed a
      significant pooled effect in favour of paraprofessionals (OR=0.34, 95% CI 0.13 to
      0.88, p=0.03), but heterogeneity was indicated (I(2)=60.9%, Chi(2)= 10.24, df=4,
      p=0.04). After correction for heterogeneity and removing one study of low
      quality, the pooling of data from three studies (n=128; mixed gender and women
      only) indicated no significant difference in effect between paraprofessionals and
      professionals (SMD=0.13, 95% CI -0.39 to 0.64; p=0.63) and a strongly significant
      pooled effect for three studies (n=188; women only) favouring paraprofessionals
      over the control condition (OR=0.30, 95% CI 0.18 to 0.48, p<0.00001), and
      homogeneity indicated between studies (I(2)=0%, Chi(2)=0.47, df=2, p=0.79).
      AUTHORS' CONCLUSIONS: The few studies included in the review did not allow
      conclusions about the effect of paraprofessionals compared to professionals.
      Pooling data from three studies, involving women only, indicated a significant
      effect for paraprofessionals (all volunteers) compared to no treatment. The
      evidence to date may justify the development and evaluation of programs
      incorporating paraprofessionals in treatment programs for anxiety and depressive
      disorders.

PMID- 15846728
TI  - Calorie and protein-enriched formula versus standard term formula for improving
      growth and development in preterm or low birth weight infants following hospital
      discharge.
AB  - BACKGROUND: Preterm and low birth weight infants are often growth-restricted at
      hospital discharge. Feeding infants post-hospital discharge with calorie and
      protein-enriched formula milk might facilitate "catch-up" growth and improve
      development. OBJECTIVES: To review the evidence from randomised controlled trials
      that feeding following hospital discharge with calorie and protein-enriched
      formula compared with standard term formula improves growth and development for
      preterm or low birth weight infants. SEARCH STRATEGY: We used the standard search
      strategy of the Cochrane Neonatal Review Group. This included searches of the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library,
      Issue 4, 2004), MEDLINE (1966 - December 2004), EMBASE (1980 - December 2004),
      CINAHL (1982 - December 2004), conference proceedings, and previous reviews.
      SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that
      compared the effect of feeding preterm or low birth weight infants post-hospital
      discharge with calorie and protein-enriched formula compared with standard term
      formula. DATA COLLECTION AND ANALYSIS: We extracted data using the standard
      methods of the Cochrane Neonatal Review Group, with separate evaluation of trial
      quality and data extraction by two authors, and synthesis of data using weighted
      mean difference and a fixed effects model for meta-analysis. MAIN RESULTS: We
      found six trials that were eligible for inclusion. These recruited a total of 424
      infants and were generally of good methodological quality. These trials found
      little evidence that feeding with calorie and protein-enriched formula milk
      affected growth and development. Because of differences in the way individual
      trials measured and presented outcomes, data synthesis was limited. Meta-analysis
      of data from two trials found a statistically significant effect on crown-heel
      length at 18 months post-term (weighted mean difference 9.7 millimetres (95%
      confidence interval 3.2 to 16.2)), but not on weight or head circumference. Meta
      analysis of data from the two trials that assessed neurodevelopment at 18 months
      post-term did not reveal a statistically significant difference in either Bayley
      Mental Development Index (weighted mean difference 0.23 (95% confidence interval 
      2.99 to 3.45)) or Psychomotor Development Index (weighted mean difference 0.56
      (95% confidence interval -1.95 to 3.07)). There are not yet any data on growth or
      development through later childhood. AUTHORS' CONCLUSIONS: The limited available
      data do not provide strong evidence that feeding preterm or low birth weight
      infants following hospital discharge with calorie and protein-enriched formula
      compared with standard term formula affects growth rates or development up to 18
      months post-term.

PMID- 15846729
TI  - Anticoagulants for the treatment of recurrent pregnancy loss in women without
      antiphospholipid syndrome.
AB  - BACKGROUND: Since hypercoagulability might result in recurrent pregnancy loss,
      anticoagulant agents could potentially increase the live-birth rate in subsequent
      pregnancies in women with either inherited thrombophilia or unexplained pregnancy
      loss. OBJECTIVES: To evaluate the efficacy and safety of anticoagulant agents,
      such as aspirin and heparin, in women with a history of at least two spontaneous
      miscarriages or one later intrauterine fetal death without apparent causes other
      than inherited thrombophilias. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group trials register (March 2004), the Central Register
      of Controlled Trials (The Cochrane Library, Issue 1, 2004), MEDLINE (January 1966
      to March 2004), and EMBASE (1980 to March 2004). We scanned bibliographies of all
      located articles for any unidentified articles. SELECTION CRITERIA: Randomised
      and quasi-randomised controlled trials that assessed the effect of anticoagulant
      treatment on the live-birth rate in women with a history of at least two
      spontaneous miscarriages or one later intrauterine fetal death without apparent
      causes other than inherited thrombophilias were eligible. Interventions included
      aspirin, unfractionated heparin, and low molecular weight heparin for the
      prevention of birth loss. One treatment could be compared with another or with
      placebo. DATA COLLECTION AND ANALYSIS: Two authors assessed the trials for
      inclusion in the review and extracted the data. Data were entered into the Review
      Manager software and double checked. MAIN RESULTS: Two studies (242 participants)
      were included in the review and for both of them data were extracted for the
      subgroups of women fulfilling the inclusion criteria of the review. In one study,
      54 pregnant women with recurrent spontaneous abortion without detectable
      anticardiolipin antibodies were randomised to low-dose aspirin or placebo.
      Similar live-birth rates were observed with aspirin and placebo (relative risk
      (RR) 1.00, 95% confidence interval (CI) 0.78 to 1.29). In another study, a
      subgroup of 20 women who had had a previous fetal loss after the 20th week and
      had a thrombophilic defect were randomised to enoxaparin or aspirin. Enoxaparin
      treatment resulted in an increased live-birth rate, as compared to low-dose
      aspirin, RR 10.00, 95% CI 1.56 to 64.20). AUTHORS' CONCLUSIONS: The evidence on
      the efficacy and safety of thromboprophylaxis with aspirin and heparin in women
      with a history of at least two spontaneous miscarriages or one later intrauterine
      fetal death without apparent causes other than inherited thrombophilias is too
      limited to recommend the use of anticoagulants in this setting. Large,
      randomised, placebo-controlled trials are urgently needed.

PMID- 15846730
TI  - Rivastigmine for vascular cognitive impairment.
AB  - BACKGROUND: Vascular dementia represents the second most common type of dementia.
      The classification of vascular dementia broadly follows three clinico
      pathological processes: multi-infarct dementia, single strategic infarct dementia
      and subcortical dementia. As not all victims fulfil strict criteria for dementia
      and may be significantly cognitively impaired without memory loss, the term
      vascular cognitive impairment is more useful. Currently, no established standard
      treatment for vascular cognitive impairment exists. Reductions in acetylcholine
      and acetyltransferase activity are common to both Alzheimer's disease and
      vascular cognitive impairment raising the possibility that cholinesterase
      inhibitors may also be beneficial for the latter. OBJECTIVES: To assess the
      efficacy of rivastigmine in the treatment of people with vascular cognitive
      impairment, vascular dementia, or mixed dementia. SEARCH STRATEGY: Trials were
      searched from the Specialized Register of the Cochrane Dementia and Cognitive
      Improvement Group on 20 December 2004 using the terms: rivastigmine, exelon, "SDZ
      ENA 713", SDZ-ENA-713. All major health care databases and many ongoing trial
      databases within the scope of the Group are searched regularly to keep this
      Register up to date. SELECTION CRITERIA: All unconfounded randomized double-blind
      trials comparing rivastigmine with placebo were eligible for inclusion. DATA
      COLLECTION AND ANALYSIS: No suitable trials were identified and thus we were
      unable to extract appropriate data or calculate summary statistics. MAIN RESULTS:
      We were unable to perform a meta-analysis given the absence of suitable trials.
      Other trials relevant to the field were identified and some indication of benefit
      in several cognitive and non-cognitive domains were noted. AUTHORS' CONCLUSIONS:
      From existing trial data there is some evidence of benefit of rivastigmine in
      vascular cognitive impairment. However, this conclusion is based on studies which
      had small numbers of patients, which sought to compare rivastigmine to treatments
      other than placebo or which used data extrapolated post hoc from large studies
      involving patients with Alzheimer's disease and vascular risk factors of unclear
      significance. Large placebo-controlled, double blind and adequately randomised
      trials are needed before firm conclusions can be drawn. The methodology of such
      trials should acknowledge the biological and clinical features unique to vascular
      cognitive impairment and its subtypes.

PMID- 15846731
TI  - Sulfasalazine for ankylosing spondylitis.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease of
      unknown cause and belongs to a group of diseases known as spondyloarthropathies
      (SpA), which includes reactive arthritis, arthritis/spondylitis in inflammatory
      bowel disease, psoriatic arthritis/spondylitis and undifferentiated SpA. Non
      steroidal anti-inflammatory drugs (NSAIDs) have been the main treatment for AS.
      For those refractory or intolerant to NSAIDs, the disease modifying antirheumatic
      drugs (DMARDs) have been used as a second line approach. Sulfasalazine (SSZ) is
      the best studied DMARD in AS, but its efficacy remains unclear. OBJECTIVES: To
      evaluate the efficacy and toxicity of sulfasalazine for the treatment of
      ankylosing spondylitis. SEARCH STRATEGY: Relevant randomised and quasi-randomised
      trials in any language were sought using the following sources: CENTRAL (Cochrane
      Central Register of Controlled Trials, Issue 2, 2003), MEDLINE (1966 to June Week
      4 2003), EMBASE (1980 to 2003 Week 26), CINAHL (1982 to June Week 3 2003) and the
      reference section of retrieved articles. SELECTION CRITERIA: We evaluated
      randomised and quasi-randomised trials examining the efficacy of sulfasalazine on
      ankylosing spondylitis. DATA COLLECTION AND ANALYSIS: Unblinded trial reports
      were reviewed independently by two reviewers according to the selection criteria.
      Disagreements on the inclusion of the studies were resolved, where necessary, by
      recourse to a third reviewer. The methodological quality of included trials were
      independently assessed by the same reviewers on randomization, concealment,
      blindness (participants, care providers and outcome investigators), description
      of withdrawals and drop-outs and intention-to-treat analysis. The same reviewers
      independently entered the data extracted from the included trials, using RevMan
      double entry facility. Results were combined using weighted mean difference or
      standardised mean difference for continuous data, and relative risk for
      dichotomous data. MAIN RESULTS: Twelve studies met the inclusion criteria but
      only eleven were included in the data analysis. The pooled analysis showed that
      the difference between intervention groups was significant only in erythrocyte
      sedimentation rate (ESR) (WMD -4.79, 95% CI -8.80 to -0.78) mm/h) and morning
      stiffness VAS-100 mm (visual analogue scale 100 mm, where 0 = no stiffness and
      100 = severe) (WMD -13.89, 95% CI -22.54 to -5.24), favouring SSZ over placebo.
      The trial with the largest sample (Clegg 1996) and that with the longest
      treatment duration (Kirwan 1993) had similar results. Both trials found that SSZ
      showed evidence of benefit in the occurrence of peripheral joint symptoms and
      peripheral responses in patients with peripheral arthritis. Nissila 1988 is the
      only trial in which SSZ showed benefit in primary outcome analyses, including
      back pain, chest expansion, occiput-to-wall test and patient's general well
      being. Compared with other trials, the patients in this trial had the shortest
      disease duration and the highest level of baseline ESR and contained the greatest
      proportion of patients with peripheral arthritis. Significantly more withdrawals
      for side effects (RR 1.50, 95% CI 1.04 to 2.15, NNH 23, 95% CI 10 to 288) and for
      any reason (RR 1.33, 95% CI 1.03 to 1.73, NNH 17, 95% CI 8 to 180) were found in
      SSZ compared with placebo group although severe side effects were rare (1 of the
      469 patients taking SSZ). AUTHORS' CONCLUSIONS: Across all AS patients, SSZ
      demonstrated some benefit in reducing ESR and easing morning stiffness, but no
      evidence of benefit in physical function, pain, spinal mobility, enthesitis,
      patient and physician global assessment. Patients at early disease stage, with
      higher level of ESR (or active disease) and peripheral arthritis might benefit
      from SSZ.

PMID- 15846732
TI  - Policy interventions implemented through sporting organisations for promoting
      healthy behaviour change.
AB  - BACKGROUND: Sporting organisations provide an important setting for health
      promotion strategies that involve policies, communication of healthy messages and
      creation of health promoting environments. The introduction of policy
      interventions within sporting organisations is one strategy to target high risk
      behaviours such as smoking, alcohol consumption, excess sun exposure, unhealthy
      eating and discrimination. OBJECTIVES: To review all controlled evaluation
      studies of policy interventions organised through sporting settings to increase
      healthy behaviour (related to smoking, alcohol, healthy eating, sun protection,
      discrimination, safety and access). SEARCH STRATEGY: We searched the Cochrane
      Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsyclNFO,
      CINAHL, SPORTDiscus, Sociological Abstracts, Dissertation Abstracts, freely
      available online health promotion and sports-related databases hosted by leading
      agencies, and the internet using sport and policy-related key words. We
      identified further studies in the bibliographies of articles and by contacting
      authors of key articles in the area. SELECTION CRITERIA: We aimed to identify
      research that had used study designs that incorporated an evaluated intervention
      and comparison. Uncontrolled studies, meeting other inclusion criteria, were to
      be reported in an annex to the review. Types of studies: Studies in which
      sporting organisations were allocated to a policy intervention or
      control/comparison group. No minimum follow-up required. TYPES OF PARTICIPANTS:
      People of all ages. Types of interventions: Any policy intervention implemented
      through sporting organisations to instigate and/or sustain healthy behaviour
      change, intention to change behaviour, or changes in attitudes, knowledge or
      awareness of healthy behaviour. Policies must address any of the following:
      smoking, alcohol, healthy eating, sun protection, access for disadvantaged
      groups, physical safety (not including injuries), and social and emotional health
      (e.g.. anti-vilification, anti-discrimination). Types of outcome measures:
      Behaviour change, intention to change behaviour, change in attitudes, knowledge
      or awareness of healthy behaviour, and policy presence. DATA COLLECTION AND
      ANALYSIS: We assessed whether identified citations were controlled evaluation
      studies and investigated the use of policy implemented in sporting settings.
      Abstracts were independently inspected by two reviewers and full papers were
      obtained where necessary. As no controlled evaluation studies were located, no
      data collection or analysis was undertaken. No uncontrolled studies meeting other
      inclusion criteria were identified and therefore no annex is presented. MAIN
      RESULTS: No rigorous studies were located to test the effectiveness of policy
      interventions organised through sporting organisations to increase healthy
      behaviours, attitudes, knowledge or inclusion of health oriented policies within
      the organisations. AUTHORS' CONCLUSIONS: We were unable to find any controlled
      studies to guide the use of policy interventions used in sporting settings. The
      search process revealed a number of case studies with anecdotal reporting of
      outcomes. We strongly recommend that rigorous evaluation techniques are employed
      more commonly in this field to illuminate the impact of health promoting policy
      on outcomes, and the contexts and processes which are likely to be effective in
      reducing harmful behaviours.

PMID- 15846733
TI  - Interventions implemented through sporting organisations for increasing
      participation in sport.
AB  - BACKGROUND: There is now compelling scientific evidence that increased levels of
      physical activity can bring wide-ranging health benefits. These benefits can
      extend beyond physical health and include other positive impacts relating to
      mental health and personal development. The sport and recreation sector is viewed
      as a priority area for increasing rates of physical activity. Participation rates
      have been shown to be lower in females, decline with age, and are reduced in
      lower socio-economic and minority groups. It is important to determine the most
      effective interventions that sporting organisations can use to increase
      participation. OBJECTIVES: To review all controlled evaluation studies of
      interventions organised through sporting settings to increase participation.
      SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials
      (CENTRAL), MEDLINE, EMBASE, PsyclNFO, CINAHL, SPORTDiscus, Sociological
      Abstracts, Dissertation Abstracts, and a number of freely-available online health
      promotion and sports-related databases. The internet was used extensively to
      search for studies and locate information generated by sporting bodies throughout
      the world. SELECTION CRITERIA: Types of studies: Controlled evaluation studies.
      No minimum follow-up required. Uncontrolled studies, meeting other inclusion
      criteria, were to be reported in an annex to the review. TYPES OF PARTICIPANTS:
      People of all ages. Types of interventions: Any intervention designed to increase
      active and/ or non-active participation in sport. These could include: mass media
      campaigns; information or education sessions; management or organisational change
      strategies; policy changes, for example to improve the socio-cultural environment
      to encourage people of specific age, gender or ethnicity to participate; changes
      to traditional or existing programs, for example club or association-initiated
      rule modification programs; provision of activities beyond traditional or
      existing programs, for example 'Come and Try' initiatives (teaser or taster
      programs); skill improvement programs; volunteer encouragement programs. Types of
      outcome measures: Change in the number of (active and non-active) participants in
      organised sport, change in status from non-participating to non-active or active
      participation, change in status from non-active to active participation. DATA
      COLLECTION AND ANALYSIS: We assessed whether identified citations were controlled
      evaluation studies which investigated the use of interventions implemented in
      sporting settings to increase participation. Two reviewers independently
      inspected abstracts. We obtained full papers where necessary. As no controlled
      evaluation studies were located, no data collection or analysis was undertaken.
      No uncontrolled studies meeting other inclusion criteria were identified and
      therefore no annex is presented. MAIN RESULTS: Despite a thorough review of the
      published and unpublished literature, we were unable to locate any rigorous
      studies which tested the effects of interventions organised through sporting
      organisations to increase participation in sport. AUTHORS' CONCLUSIONS: There is
      an absence of high quality evidence to support interventions designed and
      delivered by sporting organisations to increase participation in sport.
      Interventions funded and conducted in this area must be linked to a rigorous
      evaluation strategy in order to examine overall effectiveness, sociodemographic
      differentials in participation and cost-effectiveness of these strategies.

PMID- 15846734
TI  - Hyperbaric oxygen therapy for acute coronary syndrome.
AB  - BACKGROUND: Acute coronary syndrome (ACS) includes acute myocardial infarction
      and unstable angina. ACS is common and may prove fatal. Hyperbaric oxygen therapy
      (HBOT) will improve oxygen supply to the threatened heart and may reduce the
      volume of heart muscle that will perish. The addition of HBOT to the standard
      treatment may reduce death rate and other major adverse outcomes. OBJECTIVES: To
      assess the benefits and harms of adjunctive HBOT for treating ACS. SEARCH
      STRATEGY: We searched the following from inception to November 2004: CENTRAL,
      MEDLINE, EMBASE, CINAHL, DORCTHIM, and references from selected articles.
      Relevant journals were handsearched and researchers in the field contacted.
      SELECTION CRITERIA: Randomised studies comparing the effect on ACS of regimens
      that include HBOT with those that exclude HBOT. DATA COLLECTION AND ANALYSIS:
      Three reviewers independently evaluated the quality of trials using the
      guidelines of the Cochrane Handbook and extracted data from included trials. MAIN
      RESULTS: Four trials with 462 participants contributed to this review. There was
      a trend towards, but no significant decrease in, the risk of death with HBOT
      (relative risk (RR) 0.64, 95% CI 0.38 to 1.06, P=0.08). There was evidence from
      individual trials of reductions in the risk of major adverse coronary events
      [MACE] (RR 0.12, 95% CI 0.02 to 0.85, P=0.03; NNT 4, 95% CI 3 to 10) and some
      dysrhythmias following HBOT (RR 0.59, 95% CI 0.39 to 0.89, P=0.01; NNT 6, 95% CI
      3 to 24), particularly complete heart block (RR 0.32, 95%CI 0.12 to 0.84,
      P=0.02), and that the time to relief of pain was reduced with HBOT (Weighted Mean
      Difference [WMD] 353 minutes shorter, 95% CI 219 to 488, P<0.0001). One trial
      suggested a significant incidence of claustrophobia in single occupancy chambers
      of 15% (RR of claustrophobia with HBOT 31.6, 95%CI 1.92 to 521, P=0.02). AUTHORS'
      CONCLUSIONS: For people with ACS, individual small trials suggest the addition of
      HBOT reduced the risk of Major Adverse Cardiac Events, some dysrrhythmias, and
      reduced the time to relief from ischaemic pain, but did not reduce mortality. In
      view of the modest number of patients, methodological shortcomings and poor
      reporting, this result should be interpreted cautiously, and an appropriately
      powered trial of high methodological rigour is justified to define those patients
      (if any) who can be expected to derive most benefit from HBOT. The routine
      application of HBOT to these patients cannot be justified from this review.

PMID- 15846735
TI  - Gastro-oesophageal reflux treatment for prolonged non-specific cough in children
      and adults.
AB  - BACKGROUND: Cough is a very common symptom presenting to medical practitioners.
      Gastroesophageal reflux disease (GORD) is said to be the causative factor in up
      to 41% of adults with chronic cough. However cough and GORD are common ailments
      and their co-existence by chance is high. Also cough can induce reflux episodes.
      Treatment for GORD includes conservative measures (diet manipulation),
      pharmaceutical therapy (motility or prokinetic agents, H(2) antagonist and proton
      pump inhibitors (PPI)) and fundoplication. OBJECTIVES: To evaluate the efficacy
      of GORD treatment on chronic cough in children and adults with GORD and prolonged
      cough that is not related to an underlying respiratory disease i.e. non-specific
      chronic cough. SEARCH STRATEGY: The Cochrane Register of Controlled Trials
      (CENTRAL), the Cochrane Airways Group Specialised Register Collaboration and
      Cochrane Airways Group, MEDLINE and EMBASE databases, review articles and
      reference lists of relevant articles were searched. The date of last search was
      4th April 2004. SELECTION CRITERIA: All randomised controlled trials on GORD
      treatment for cough in children and adults without primary lung disease. DATA
      COLLECTION AND ANALYSIS: Results of searches were reviewed against pre-determined
      criteria for inclusion. Two independent reviewers selected, extracted and
      assessed data for inclusion. Authors were contacted for further information. Data
      was analysed as "intention to treat" as well as "treatment received". Paediatric
      and adults data were considered separately. Sensitivity analyses were performed.
      MAIN RESULTS: 11 studies (3 paediatric, 8 adults; 383 participants) were
      included. None of the paediatric studies could be included in meta-analysis. In
      adults, analysis on use of H(2) antagonist, motility agents and conservative
      treatment for GORD were not possible (from lack of data) and there were no
      controlled studies on fundoplication as an intervention. Five adult studies
      comparing PPI (2-3 months) to placebo were analysed for various outcomes in the
      meta-analysis. Enrollment of subjects for two studies were primarily from medical
      clinics and another three studies were otolaryngeal clinic patients. Using
      "intention to treat", pooled data from three studies resulted in no significant
      difference between treatment and placebo in total resolution of cough. Pooled
      data revealed no significant improvement in cough outcomes (end of trial or
      change in cough scores). Significant differences were only found in sensitivity
      analysis. A significant improvement in change of cough scores was found in end of
      intervention (2-3 months) in those receiving PPI with a standardised mean
      difference of -0.41 (95%CI -0.75, -0.07) using GIV analysis on cross over trials.
      Two studies reported improvement in cough after 5 days to 2 weeks of treatment.
      Significant heterogeneity was found between studies using omeprazole and other
      PPIs. AUTHORS' CONCLUSIONS: There is insufficient evidence to definitely conclude
      that GORD treatment with PPI is beneficial for cough associated with GORD in
      adults. The beneficial effect was only seen in sub-analysis and its effect was
      small. The optimal duration of such a trial of therapy to evaluate response could
      not be ascertained in the meta-analysis although two RCTs reported significant
      change by two weeks of therapy. Clinicians should be cognisant of a period
      (natural resolution with time) and placebo effect in studies that utilise cough
      as an outcome measure. Data in children are inconclusive. Future paediatric and
      adult studies are needed whereby studies should be double blind, randomised
      controlled, parallel design, using treatments for at least two months, with
      validated subjective and objective cough outcomes and include ascertainment of
      time to respond as well as assessment of acid and/or non acid reflux whilst on
      therapy.

PMID- 15846736
TI  - Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and
      24 months old.
AB  - BACKGROUND: Acute bronchiolitis is the leading causes of medical emergencies
      during winter in children younger than two years of age. Chest physiotherapy is
      thought to assist infants in the clearance of secretions and decrease ventilatory
      effort. OBJECTIVES: To determine the efficacy and safety of chest physiotherapy
      in infants aged less than 24 months old with acute bronchiolitis. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library Issue 2, 2004) which contains the Acute
      Respiratory Infection Group's specialised register; MEDLINE (January 1966 to June
      2004); EMBASE (1990 to June 2004); PASCAL; SCISEARCH; LILACS; and Cumulative
      Index to the Nursing & Allied Health Literature (CINAHL) (1982 to May 2004).
      SELECTION CRITERIA: Randomised controlled trails (RCTs) in paediatric patients
      younger than twenty four months old in which chest physiotherapy was compared
      against no intervention or against another type of physiotherapy. DATA COLLECTION
      AND ANALYSIS: Two independent reviewers extracted the data. Primary outcome was a
      severity clinical score. Secondary outcomes were length of hospital stay,
      duration of oxygen supplementation, and the use of bronchodilators and steroids.
      MAIN RESULTS: Three clinical trials met the inclusion criteria. All evaluated
      vibration and percussion techniques in postural drainage positions compared to no
      intervention. The study population were hospitalised infants with a clinical
      diagnosis of acute bronchiolitis, although one study included only infants who
      required nasogastric tube feeding or intravenous fluids. None of the other
      included trails observed any differences in the severity of the clinical score at
      day five or during each of the five days of the trial or until discharge, length
      of hospital stay, or oxygen requirements between chest physiotherapy group and
      control. AUTHORS' CONCLUSIONS: Based on the results of three RCTs, chest
      physiotherapy using vibration and percussion techniques does not reduce length of
      hospital stay, oxygen requirements, or improve the severity clinical score in
      infants with acute bronchiolitis that are not under mechanical ventilation, and
      who do not have any other co-morbidity. Chest physiotherapy using forced
      expiratory technique needs to be evaluated by clinical research.

PMID- 15846737
TI  - Intramedullary nails for extracapsular hip fractures in adults.
AB  - BACKGROUND: Intramedullary nails may be used for the surgical fixation of
      extracapsular hip fractures in adults. They may be inserted from the top
      (cephalocondylic) or from the bottom (condylocephalic) end of the femur.
      OBJECTIVES: To compare different types or design modifications of intramedullary
      nails used in the fixation of extracapsular hip fractures. SEARCH STRATEGY: We
      searched the Cochrane Musculoskeletal Injuries Group specialised register
      (September 2004), the Cochrane Central Register of Controlled Trials (The
      Cochrane Library Issue 3, 2004), MEDLINE (1966 to September week 1 2004), EMBASE
      (1988 to 2004 Week 37), the UK National Research Register Issue 2, 2004, several
      orthopaedic journals, conference proceedings and reference lists of articles.
      SELECTION CRITERIA: All randomised or quasi-randomised trials comparing different
      types of intramedullary nails or modifications to the design of intramedullary
      nails in the treatment of extracapsular hip fractures in adults. DATA COLLECTION
      AND ANALYSIS: Both authors independently assessed trial quality and extracted
      data. Additional information was sought from all trialists. MAIN RESULTS: Four
      studies, involving a total of 834 predominantly female and older patients with
      mainly unstable trochanteric fractures, were included. All trials compared
      different designs of cephalocondylic nail. Allocation concealment was likely in
      one trial, not described in two and not done in the fourth. Two studies, with 674
      participants, compared the proximal femoral nail versus the Gamma nail. Blood
      transfusion was greater for the proximal femoral nail group in one trial, yet
      blood loss was less in this group in the other trial. Pooled data for re
      operation (relative risk 1.08, 95% confidence interval 0.65 to 1.81) and
      mortality (relative risk 1.24, 95% confidence interval 0.90 to 1.71) showed no
      statistically significant differences between the two groups. Limited data for
      long term function also showed no statistically significant differences. The two
      other studies, with 80 participants each, found respectively no differences
      between a gliding nail versus a Gamma nail; and a dynamically versus a statically
      locked intramedullary hip screw. AUTHORS' CONCLUSIONS: The limited evidence from
      the randomised trials undertaken to date is insufficient to determine if there
      are important differences in outcome between different designs of intramedullary
      nails used in the internal fixation of extracapsular hip fractures. Given the
      evidence of superiority of the sliding hip screw compared with intramedullary
      nails for extracapsular hip fractures, further studies comparing different
      designs of intramedullary nails are not a priority. Any new design should be
      evaluated in a randomised comparison with the sliding hip screw.

PMID- 15846738
TI  - Antibiotic use for irreversible pulpitis.
AB  - BACKGROUND: Irreversible pulpitis, which is characterised by acute and intense
      pain, is one of the most frequent reasons that patients attend for emergency
      dental care. Apart from removal of the tooth the customary way of relieving the
      pain of irreversible pulpitis is by drilling into the tooth, removing the
      inflamed pulp (nerve) and cleaning the root canal. However, a significant
      minority of dentists continue to prescribe antibiotics to stop the pain of
      irreversible pulpitis. OBJECTIVES: The objective of this review was to provide
      reliable evidence regarding the effectiveness of prescribing systemic antibiotics
      for irreversible pulpitis by comparing clinical outcomes expressed as pain
      relief. SEARCH STRATEGY: We searched the following databases: Cochrane Oral
      Health Group Trials Register and Pain, Palliative Care and Supportive (PaPaS)
      Care Group Trials Register to 6th September 2004; the Cochrane Central Register
      of Controlled Trials (CENTRAL) The Cochrane Library Issue 3 2004; MEDLINE (1966
      to 6th September 2004); EMBASE (1980 to week 36 2004). SELECTION CRITERIA: This
      review includes one randomised controlled trial which compared pain relief with
      systemic antibiotics and analgesics, against placebo and analgesics in the acute
      preoperative phase of irreversible pulpitis. DATA COLLECTION AND ANALYSIS: Only
      one trial is included in this review, therefore pooling of data from studies was
      not possible and a descriptive summary is presented. MAIN RESULTS: One trial
      involving 40 participants was included in this review. There was a close parallel
      distribution of the pain ratings in both the intervention and placebo groups over
      the 7 day study period. The between-group differences in sum pain intensity
      differences (SPID) for the penicillin group were (6.0+/-10.5), and for placebo
      (6.0+/-9.5) P = 0.776. The sum pain percussion intensity differences (SPPID) for
      the penicillin group were (3.5+/-7.5) and placebo (2.0+/-7.0) P = 0.290, with
      differences as assessed by the Mann-Whitney-Wilcoxon test considered to be
      statistically significant at P < 0.05. There was no significant difference in the
      mean total number of ibuprofen tablets (P = 0.839) and Tylenol tablets (P =
      0.325), in either group over the study period. The administration of penicillin
      over placebo did not appear to significantly reduce the quantity of analgesic
      medication taken (P > 0.05) for irreversible pulpitis. AUTHORS' CONCLUSIONS: This
      review which was based on one methodologically sound but low powered small sample
      trial provided some evidence that there is no significant difference in pain
      relief for patients with untreated irreversible pulpitis who did or did not
      receive antibiotics in addition to analgesics.

PMID- 15846739
TI  - Quit and Win contests for smoking cessation.
AB  - BACKGROUND: Quit and Win contests were developed in the 1980s by the Minnesota
      Heart Health Program, and have been widely used since then as a population-based
      smoking cessation intervention at local, national and international level. Since
      1994 an international contest has been held every two years in as many as 80
      countries (2002). OBJECTIVES: To determine whether quit and win contests can
      deliver higher long-term quit rates than baseline community quit rates. To assess
      the impact of such programmes, we considered both the quit rates achieved by
      participants, and the population impact, which takes into account the proportion
      of the target population entering the contest. SEARCH STRATEGY: We searched the
      Cochrane Tobacco Addiction Group specialized register, with additional searches
      of MEDLINE (January 1966 to September 2004), EMBASE (180 to 2004/8), CINAHL (1982
      to 2004/8) and PsycINFO (1872 to 2004/6). Search terms included competition*,
      quit and win, quit to win, contest*, prize*. SELECTION CRITERIA: We considered
      randomized controlled trials, allocating individuals or communities to
      experimental or control conditions. We also considered controlled studies with
      baseline and post-intervention measures. DATA COLLECTION AND ANALYSIS: Data were
      extracted by one author and checked by the second. We contacted study authors for
      additional data where necessary. The main outcome measure was abstinence from
      smoking for at least six months from the start of the intervention. We used the
      most rigorous definition of abstinence in each trial, and biochemically validated
      rates where available. We decided against performing a meta-analysis, because of
      the heterogeneity of the included studies, and the small number of scientifically
      valid studies. MAIN RESULTS: Four studies met our inclusion criteria. Three
      demonstrated significantly higher quit rates (8% to 20%) for the quit and win
      group than for the control group at the 12-month assessment. However, the
      population impact measure, where available, suggests that the effect of contests
      on community prevalence of smoking is small, with fewer than one in 500 smokers
      quitting because of the contest. Levels of deception, where they could be
      quantified, were high. Although surveys suggest that international quit and win
      contests may be effective, especially in developing countries, the lack of
      controlled studies precludes any firm conclusions from this review. AUTHORS'
      CONCLUSIONS: Quit and win contests at local and regional level appear to deliver
      quit rates above baseline community rates, although the population impact of the
      contests seems to be relatively low. Contests may be subject to levels of
      deception which could compromise the validity of the intervention. International
      contests may prove to be an effective mechanism, particularly in developing
      countries, but a lack of well-designed comparative studies precludes any firm
      conclusions.

PMID- 15846740
TI  - Interventions for preventing bone disease in kidney transplant recipients.
AB  - BACKGROUND: Patients with chronic kidney disease have significant abnormalities
      of bone remodelling and calcium homeostasis and are at increased risk of
      fracture. The fracture risk for a kidney transplant recipient is four times that
      of the general population and higher than that for a patient on dialysis. Trials
      reporting the use of bisphosphonates, vitamin D analogues, calcitonin, and
      hormone replacement therapy to treat bone disease following engraftment exist.
      OBJECTIVES: To evaluate the use of interventions for the treatment of bone
      disease following kidney transplantation. SEARCH STRATEGY: The Cochrane CENTRAL
      Register of Controlled Trials (The Cochrane Library - Issue 3 2004), MEDLINE
      (1966 to August 2004), EMBASE (1980- August 2004) and reference lists were
      searched without language restriction. SELECTION CRITERIA: Randomised trials of
      treatment of bone disease following kidney transplantation were included. Trials
      of recipients of any transplant other than a kidney transplant including trials
      of kidney-pancreas transplants were excluded. DATA COLLECTION AND ANALYSIS: Two
      authors assessed independently trial quality and extracted data. Statistical
      analyses were performed using the random effects model and the results expressed
      as relative risk (RR) with 95% confidence intervals (CI) for dichotomous
      variables. For continuous variables the weighted mean difference (WMD) and its
      95% CI was used. MAIN RESULTS: Twenty-three eligible trials (1,209 patients) were
      identified. Seven trials compared more than two interventions. Nineteen trials
      compared active treatment with placebo, five vitamin D analogue and calcium, six
      vitamin D analogue alone, twelve bisphosphonates, and four nasal calcitonin.
      Eight trials compared two active treatments, one 17-beta oestradiol and
      medroxyprogesterone versus vitamin D analogue, five bisphosphonate versus vitamin
      D analogue, two vitamin D analogue and calcium versus calcium and one
      bisphosphonate versus calcitonin. Methodological quality was suboptimal. There
      were no significant differences between any treatment group for risk of fracture.
      Bisphosphonate, administered by any route, vitamin D analogue and calcitonin all
      had a beneficial effect on the bone mineral density at the lumbar spine.
      Bisphosphonates and vitamin D analogue had a beneficial effect on the bone
      mineral density at the femoral neck. Few or no data were available for combined
      hormone replacement, testosterone, selective oestrogen receptor modulators,
      fluoride or anabolic steroids. All-cause mortality and drug-related toxicity were
      reported infrequently and there was no statistical difference between treatment
      groups. AUTHORS' CONCLUSIONS: No benefit from any intervention known to reduce
      risk of fracture from bone disease could be demonstrated to reduce fracture
      incidence in kidney transplant recipients.

PMID- 15846741
TI  - Family therapy for attention-deficit disorder or attention-deficit/hyperactivity
      disorder in children and adolescents.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is diagnosed in
      between 3% and 7% of school-age children and consists of the core symptoms of
      inattention, impulsivity and hyperactivity. Children are often treated with
      medication, usually stimulant medication such as methylphenidate. Stimulant
      medication has been found to be effective for alleviating ADHD symptoms, at least
      in the short term. ADHD is also treated with a variety of psychosocial and
      psychoeducational interventions for parents, children, and with multicomponent
      interventions combined with medication management. However, many patients (10 to
      13% of patients) cannot or prefer not to take medication. Family therapy without
      medication may help to develop structure in the family, help to manage children's
      behaviour, and may help families cope with distress from the presence of the
      disorder. OBJECTIVES: This review seeks to address the question of whether family
      therapy without medication can reduce the core symptoms of ADHD as compared to no
      treatment or standard treatment. SEARCH STRATEGY: The following electronic
      databases were searched using a specific search strategy: The Cochrane Central
      Register of Controlled Trials (The Cochrane Library Issue 3, 2004), MEDLINE (1966
      to April 2004), PsycINFO (1872 to April 2004), CINAHL (1982 to April 2004),
      Biosis (Biological Abstracts) (1985 to March 2004), Dissertation Abstracts (1980
      to April 2004), and Sociological Abstracts (Sociofile) (1963 to April 2004). Hand
      searches of relevant journals and bibliographies were also conducted and experts
      in the field were contacted for further information. SELECTION CRITERIA: Included
      studies were randomised controlled trials investigating the efficacy of
      behavioural family therapy, cognitive behavioural family therapy, or functional
      family therapy for children with ADHD or ADD (Attention Deficit Disorder). DATA
      COLLECTION AND ANALYSIS: Studies were evaluated for methodological quality and to
      determine whether they met the inclusion criteria. MAIN RESULTS: This assessment
      yielded two studies. Data were extracted for both studies. The findings from
      Jensen 1999 (N=579) indicate that no difference can be detected between the
      efficacy of behavioural family therapy and treatment as usual in the community.
      The finding from the available data from Horn 1991 slightly favours treatment
      over medication placebo. AUTHORS' CONCLUSIONS: Further research examining the
      effectiveness of family therapy versus a no-treatment control condition is needed
      to determine whether family therapy is an effective intervention for children
      with ADHD. There were no results available from studies investigating forms of
      family therapy other than behavioural family therapy.

PMID- 15846742
TI  - Self-monitoring of blood glucose in patients with type 2 diabetes mellitus who
      are not using insulin.
AB  - BACKGROUND: Self-monitoring of blood glucose (SMBG) has been found to be
      effective for patients with type 1 diabetes and for patients with type 2 diabetes
      using insulin. There is much debate on the effectiveness of SMBG as a tool in the
      self-management for patients with type 2 diabetes who are not using insulin.
      OBJECTIVES: The objective of this review was to assess the effects of SMBG in
      patients with type 2 diabetes mellitus who are not using insulin. SEARCH
      STRATEGY: Studies were obtained from searches of multiple electronic
      bibliographic databases supplemented with hand searches of references of
      retrieved articles. Date of last search: September 2004. SELECTION CRITERIA: We
      included randomised controlled trails investigating the effects of SMBG compared
      with usual care and/or with self-monitoring of urine glucose in patients with
      type 2 diabetes who where not using insulin. Included studies should have used at
      least one of the following outcome measures: glycaemic control, quality of life,
      well-being, patient satisfaction, or hypoglycaemic episodes. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently extracted data from included studies and
      assessed study quality. Data from the studies were compared to decide whether
      they were sufficiently homogeneous to pool in a meta-analysis. MAIN RESULTS: Six
      randomised controlled trials were included in the review. Four trials compared
      SMBG with usual care, one trial compared SMBG with self-monitoring of urine
      glucose and there was one three-armed trial comparing SMBG with self-monitoring
      of urine glucose and usual care. Because of the differences in patient
      characteristics, interventions and outcomes between the studies, it was not
      possible to perform a meta-analysis. The methodological quality of studies was
      low. Two of the six studies reported a significant lowering effect of self
      monitoring of blood glucose on HbA1c. However, one of these studies had a co
      intervention with education on diet and lifestyle. There were few data on the
      effects of other outcomes and these effects were not statistically significant.
      AUTHORS' CONCLUSIONS: From this review we concluded that self-monitoring of blood
      glucose might be effective in improving glycaemic control in patients with type 2
      diabetes who are not using insulin. To assess the potential beneficial effects of
      SMBG in these patients a large and well-designed randomised controlled trial is
      required. This long-term trial should also investigate patient-related outcomes
      like quality of life, well-being and patient satisfaction, and provide adequate
      education to the patient to allow SMBG to be effective.

PMID- 15846743
TI  - Prophylactic cranial irradiation for preventing brain metastases in patients
      undergoing radical treatment for non-small cell lung cancer.
AB  - BACKGROUND: In non-small cell lung cancer (NSCLC), there is a relatively high
      incidence of brain metastases following radical treatment. At present, the role
      of prophylactic cranial irradiation (PCI) in this group of patients is not clear.
      OBJECTIVES: To investigate whether PCI has a role in the management of patients
      with NSCLC treated with radical intent. SEARCH STRATEGY: The electronic databases
      MEDLINE, EMBASE and Cancerlit, along with handsearching of journals, relevant
      books, and review articles used to identify potentially eligible trials.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing PCI with no PCI
      in NSCLC patients treated with radical intent. DATA COLLECTION AND ANALYSIS: Four
      RCTs were reviewed. Due to the small patient numbers, and variations in
      radiotherapy (RT) dose, no meta-analysis was attempted. MAIN RESULTS: PCI may
      reduce the incidence of brain metastases, but there is no evidence of a survival
      benefit. There is no evidence that any regimen is superior, and the effect of PCI
      on quality of life (QOL) is not known. AUTHORS' CONCLUSIONS: There is
      insufficient evidence to support the use of PCI in clinical practice. Where
      possible, patients should be offered entry into a clinical trial.

PMID- 15846744
TI  - Complementary and miscellaneous interventions for nocturnal enuresis in children.
AB  - BACKGROUND: Nocturnal enuresis (bedwetting) is a socially disruptive and
      stressful condition which affects around 15 to 20% of five year olds, and up to
      2% of young adults. OBJECTIVES: To assess the effects of complementary
      interventions and others such as surgery or diet on nocturnal enuresis in
      children, and to compare them with other interventions. SEARCH STRATEGY: We
      searched the Cochrane Incontinence Group Specialised Register (searched 22
      November 2004), the Traditional Chinese Medical Literature Analysis and Retrieval
      System (TCMLARS) (January 1984 to June 2004) and the reference lists of relevant
      articles. SELECTION CRITERIA: All randomised or quasi-randomised trials of
      complementary and other miscellaneous interventions for nocturnal enuresis in
      children were included except those focused solely on daytime wetting. Comparison
      interventions could include no treatment, placebo or sham treatment, alarms,
      simple behavioural treatment, desmopressin, imipramine and miscellaneous other
      drugs and interventions. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently assessed the quality of the eligible trials, and extracted data.
      MAIN RESULTS: In 15 randomised controlled trials, 1389 children were studied, of
      whom 703 received a complementary intervention. The quality of the trials was
      poor: four trials were quasi-randomised, five showed differences at baseline and
      ten lacked follow up data. The outcome was better after hypnosis than imipramine
      in one trial (relative risk (RR) for failure or relapse after stopping treatment
      0.42, 95% confidence interval (CI) 0.23 to 0.78). Psychotherapy appeared to be
      better in terms of fewer children failing or relapsing than both alarm (RR 0.28,
      95% CI 0.09 to 0.85) and rewards (0.29, 95% 0.09 to 0.90) but this depended on
      data from only one trial. Acupuncture had better results than sham control
      acupuncture (RR for failure or relapse after stopping treatment 0.67, 95% CI 0.48
      to 0.94) in a further trial. Active chiropractic adjustment had better results
      than sham adjustment (RR for failure or relapse after stopping treatment 0.74,
      95% CI 0.60 to 0.91). However, each of these findings came from small single
      trials, and need to be verified in further trials. The findings for diet and
      faradization were unreliable, and there were no trials including homeopathy or
      surgery. AUTHORS' CONCLUSIONS: There was weak evidence to support the use of
      hypnosis, psychotherapy, acupuncture and chiropractic but it was provided in each
      case by single small trials, some of dubious methodological rigour. Robust
      randomised trials are required with efficacy, cost-effectiveness and adverse
      effects carefully monitored.

PMID- 15846745
TI  - Risperidone versus olanzapine for schizophrenia.
AB  - BACKGROUND: Antipsychotic medication is a mainstay of treatment for schizophrenia
      and risperidone and olanzapine are the most popular treatment choice of the new
      generation drugs. OBJECTIVES: To determine the clinical effects, safety and cost
      effectiveness of risperidone compared with olanzapine for treating schizophrenia.
      SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (June
      2004) which is based on regular searches of, amongst others, BIOSIS, CENTRAL,
      CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were
      inspected for further trials. We also contacted relevant pharmaceutical companies
      for additional information. SELECTION CRITERIA: We included all clinical
      randomised trials comparing risperidone with olanzapine for schizophrenia and
      schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data
      independently. For homogenous dichotomous data we calculated random effects,
      relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers
      needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data,
      we calculated weighted mean differences (WMD). MAIN RESULTS: We found no
      difference for the outcome of unchanged or worse in the short term (n=548, 2
      RCTs, RR 1.00 CI 0.88 to 1.15). One study, sponsored by the manufactures of
      olanzapine, favoured this drug for the outcome of relapse/rehospitalisation by 12
      months (n=279, RR 2.16 CI 1.31 to 3.54, NNT 7 CI 4 to 25). Most mental state data
      showed the two drugs to as effective as each other (n=552, 2 RCTs, RR 'no <20%
      decrease PANSS by eight weeks' 1.01 CI 0.87 to 1.16). At least two thirds of
      people given risperidone or olanzapine experienced an adverse event (n=300, 2
      RCTs, RR 1.16 CI 0.70 to 1.94). About 20% had anticholinergic symptoms (n=719, 3
      RCTs, RR 1.12 CI 0.77 to 1.63) and 20% of both groups experienced insomnia
      (n=594, 3 RCTs, RR 1.33 CI 0.95 to 1.85) and approximately 33% sleepiness (n=719,
      4 RCTs, 0.99 CI 0.79 to 1.23). One third of people given either drug experienced
      some extrapyramidal symptoms (n=893, 3 RCTs, RR 1.18 CI 0.75 to 1.88) but 25% of
      people using risperidone require medication to alleviate extrapyramidal adverse
      effects (n=419, 2 RCTs, RR 1.76 CI 1.25 to 2.48, NNH 8 CI 4 to 25). People
      allocated to risperidone were less likely to gain weight compared with those
      given olanzapine and the weight gain resulting from olanzapine can be
      considerable and of rapid onset (n=377, 1 RCT, RR gain more than 7% of their
      baseline weight 0.40 CI 0.23 to 0.70, NNT 8 CI 6 to 17). Risperidone may cause
      more sexual dysfunction than olanzapine (n=370, 2 RCTs, RR abnormal ejaculation
      4.36 CI 1.38 to 13.76, NNH 20 CI 6 to 176; n=31, 1 RCT, RR impotence 2.43 CI 0.24
      to 24.07). Within trials both drugs are associated with equal attrition (n=1217,
      7 RCTs, RR leaving the study early 1.17 CI 0.92 to 1.49). AUTHORS' CONCLUSIONS:
      Data regarding quality of life and economic outcomes are difficult to interpret,
      and for both these highly marketed new drugs we know very little from evaluative
      studies regarding service outcomes, general functioning and behaviour, engagement
      with services and treatment satisfaction. There is little to differentiate
      between risperidone and olanzapine except on the issue of adverse effects and
      both these drugs have unpleasant adverse effects. Risperidone is particularly
      associated with movement disorders and sexual dysfunction. Olanzapine can cause
      considerable rapid weight gain.This review highlights the need for large,
      independent, well designed, conducted and reported pragmatic randomised studies.

PMID- 15846746
TI  - Neoadjuvant chemotherapy for invasive bladder cancer.
AB  - BACKGROUND: Controversy exists as to whether neoadjuvant chemotherapy improves
      survival in patients with invasive bladder cancer, despite randomised controlled
      trials (RCTs) involving over 3000 patients. OBJECTIVES: To conduct a systematic
      review and meta-analysis of individual patient data to evaluate the effect of
      neoadjuvant chemotherapy on survival in patients with this invasive bladder
      cancer. SEARCH STRATEGY: MEDLINE and Cancerlit searches were supplemented with
      information from registers and by hand searching meeting proceedings and also by
      discussion with relevant trialists and organisations. These have been regularly
      updated until June 2003. SELECTION CRITERIA: Trials that aimed to randomise
      patients with biopsy proven invasive (i.e. clinical stage T2-T4a) transitional
      cell carcinoma of the bladder to receive local definitive treatment with or
      without neoadjuvant chemotherapy were eligible for inclusion. DATA COLLECTION AND
      ANALYSIS: We collected, validated and re-analysed updated data on all randomised
      patients from all available randomised trials, including 3005 patients from 11
      RCTs. For all outcomes, we obtained overall pooled hazard ratios using the fixed
      effects model. To explore the potential impact of trial design we pre-planned
      analyses that grouped trials by important aspects of their design that might
      influence the treatment effect. To investigate any differences in effect by pre
      defined patient subgroups we used a stratified logrank analysis on the primary
      endpoint of survival. MAIN RESULTS: These results include data from one extra
      trial and so update those in the original publication ABC 2003. Platinum based
      combination chemotherapy showed a significant benefit on overall survival with a
      combined hazard ratio (HR) 0.86 (95% CI 0.77 to 0.95, p=0.003); 14% reduction in
      the risk of death; 5% absolute benefit at 5 years (95% CI 1 to 7%); overall
      survival increased from 45% to 50%. This effect was observed irrespective of the
      type of local treatment and did not vary between subgroups of patients. The HR
      for all trials, including those that used single-agent cisplatin, tended to
      favour neoadjuvant chemotherapy (HR= 0.89, 95% CI 0.81 to 0.98, p=0.022).
      Although platinum based combination chemotherapy was beneficial, there was no
      clear evidence to support the use of single-agent platinum, indeed there was
      significant difference in the effect between these groups of trials (p=0.029).
      AUTHORS' CONCLUSIONS: This improvement in survival encourages the use of platinum
      based combination chemotherapy for patients with invasive bladder cancer.

PMID- 15846747
TI  - Early introduction of lipids to parenterally-fed preterm infants.
AB  - BACKGROUND: Lipids are essential components of parenteral nutrition for preterm
      infants. Parenteral lipids can be administered through a peripheral vein, and
      their early introduction offers the potential advantages of increasing energy
      intake and providing essential fatty acids and fat soluble vitamins. Concerns
      have been raised about potential adverse effects including chronic lung disease
      (CLD), increase in pulmonary vascular resistance, impaired pulmonary gas
      diffusion, bilirubin toxicity, sepsis and free radical stress. OBJECTIVES: To
      determine the safety and efficacy of 'early' (</= 5 days after birth)
      introduction of lipids to parenterally fed preterm infants. SEARCH STRATEGY:
      Eligible studies were identified by searching MEDLINE (December 2004), EMBASE
      1980 - 2004, Oxford Database of Perinatal Trials, Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2004) and CINAHL
      (December 1982 - December 2004). Abstracts of the Society for Pediatric Research
      were hand searched from 1980 to 2004 inclusive. No language restrictions were
      applied. SELECTION CRITERIA: All randomised or quasi randomised controlled trials
      comparing 'early' versus 'no early' introduction of lipids to preterm infants.
      DATA COLLECTION AND ANALYSIS: Data were sought regarding effects on growth and
      risk of CLD or death, other respiratory morbidities including duration of
      respiratory support, duration of supplemental oxygen, the need for home oxygen,
      pneumothorax (PTX), pulmonary haemorrhage and pulmonary interstitial emphysema
      (PIE), >/= stage 2 necrotizing enterocolitis (NEC), retinopathy of prematurity
      (ROP), patent ductus arteriosus (PDA), sepsis, intraventricular haemorrhage
      (IVH), clinically significant thrombocytopenia and significant jaundice.
      Methodological quality of eligible studies was assessed according to allocation
      concealment, blinding of intervention, blinding of outcome assessment and
      completeness of follow up. When appropriate, meta-analysis was conducted to
      provide a pooled estimate of effect. For categorical data the Typical relative
      risk (RR), Typical risk difference (RD) and number needed to treat (NNT) with 95%
      confidence intervals (CI) were calculated. Continuous data were analysed using
      weighted mean difference (WMD). MAIN RESULTS: Five studies (n = 397) were
      included in the review. All studies compared the effectiveness and safety of
      'early' introduction versus 'no early' introduction of lipids in preterm infants.
      The timing of introduction of 'early lipids' ranged from < 12 hours after birth
      to day five of life. The timing of introduction of lipids in the 'no early' lipid
      group ranged from day six after birth to day 14 after birth. The initial dose
      ranged from 0.5 - 1 g/kg/day with gradual daily increments up to a maximum of 2.5
      - 3.5 g/kg/day. For the primary outcomes (growth, death and CLD), there was no
      statistically significant difference between the 'early' lipid and 'no early'
      lipid groups. Days to regain birth weight: [WMD 0.59 (95% CI -2.41, 3.58); two
      trials; N = 71]. Rate of weight gain (g/day) during period of hospital stay: [MD 
      2.40 (95% CI -5.30, 0.50); one trial; N = 129]Death (irrespective of time):
      [Typical RR 1.04 (95% CI 0.69, 1.56); Typical RD 0.01 (95% CI -0.07, 0.08); five
      trials; N = 397]Neonatal deaths: [Typical RR 1.35 (95% CI 0.78, 2.34); Typical RD
      0.05 (95% CI -0.04, 0.13); four trials; N = 268].CLD: [Typical RR 1.10 (95% CI
      0.81, 1.49); Typical RD 0.04 (95% CI -0.09, 0.17); two trials; N = 193]. For the
      secondary outcomes of other respiratory morbidities including duration of
      respiratory support, duration of supplemental oxygen, PTX, pulmonary haemorrhage,
      PIE, NEC, ROP, PDA, sepsis, IVH and significant jaundice, there were no
      statistically significant differences between 'early' and 'no early' lipid
      groups. AUTHORS' CONCLUSIONS: No statistically significant effects of 'early
      introduction' of lipids on short term nutritional or other clinical outcomes,
      either benefits or adverse effects, were demonstrated in the studies reviewed.
      Based on the currently available evidence, 'early' initiation of lipids (</= 5
      days after birth) can not be recommended for short term growth or to prevent
      morbidity and mortality in preterm infants.

PMID- 15846748
TI  - Long-term non-pharmacological weight loss interventions for adults with
      prediabetes.
AB  - BACKGROUND: Most persons with prediabetes (impaired glucose tolerance or impaired
      fasting glucose) are overweight, and obesity worsens the metabolic and
      physiologic abnormalities associated with this condition. Prediabetes is an
      important risk factor for the development of type 2 diabetes. OBJECTIVES: The
      objective of this review was to assess the effectiveness of dietary, physical
      activity, and behavioral weight loss, and weight control interventions for adults
      with prediabetes. SEARCH STRATEGY: Studies were obtained from computerized
      searches of multiple electronic bibliographic databases, supplemented by hand
      searches of selected journals, and consultation with experts in obesity research.
      The last search was conducted May, 2004. SELECTION CRITERIA: Studies were
      included if they were published or unpublished randomized controlled trials in
      any language and examined weight loss or weight control strategies using one or
      more dietary, physical activity, or behavioral interventions, with a follow-up
      interval of at least 12 months. DATA COLLECTION AND ANALYSIS: Effects were
      combined using a random-effects model. MAIN RESULTS: Nine studies were
      identified, with a total of 5,168 participants. Follow-up ranged from 1 to 10
      years. Quantitative synthesis was limited by the heterogeneity of populations,
      settings, and interventions and by the small number of studies that examined
      outcomes other than weight. Overall, in comparisons with usual care, four studies
      with a follow-up of one year reduced weight by 2.8 kg (95 % confidence interval
      (CI) 1.0 to 4.7) (3.3% of baseline body weight) and decreased body mass index by
      1.3 kg/m(2) (95% CI 0.8 to 1.9). Weight loss at two years was 2.6 kg (95% CI 1.9
      to 3.3) (three studies). Modest improvements were noted in the few studies that
      examined glycemic control, blood pressure, or lipid concentrations (P > 0.05). No
      data on quality of life or mortality were found. The incidence of diabetes was
      significantly lower in the intervention groups versus the controls in three of
      five studies examining this outcome at 3 to 6 years follow-up. AUTHORS'
      CONCLUSIONS: Overall, weight loss strategies using dietary, physical activity, or
      behavioral interventions produced significant improvements in weight among
      persons with prediabetes and a significant decrease in diabetes incidence.
      Further work is needed on the long-term effects of these interventions on
      morbidity and mortality and on how to implement these interventions in diverse
      community settings.

PMID- 15846749
TI  - Biocompatible hemodialysis membranes for acute renal failure.
AB  - BACKGROUND: Acute renal failure (ARF) is associated with substantial morbidity
      and mortality. Some trials have reported a survival advantage among patients
      dialyzed with biocompatible membranes (BCM) compared to bioincompatible membranes
      (BICM). These findings were not consistently observed in subsequent studies.
      OBJECTIVES: To ascertain whether the use of BCM confers an advantage in either
      survival or recovery of renal function over the use of BICM in adult patients
      with ARF requiring intermittent hemodialysis. SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library 
      Issue 1, 2004), MEDLINE (1966 to January 2004), EMBASE (1980 to January 2004),
      the Mexican Index of Latin American Biomedical Journals IMBIOMED (1990 to January
      2004), the Latin American and Caribbean Health Sciences Literature Database
      LILACS (1982 to January 2004), and reference lists of articles. SELECTION
      CRITERIA: Randomized and quasi-randomized controlled trials comparing the use of
      a BCM with a BICM in patients > 18 years of age with ARF requiring intermittent
      hemodialysis. DATA COLLECTION AND ANALYSIS: Two authors extracted the data
      independently. Cellulose-derived dialysis membranes were classified as BICM, and
      synthetic dialyzers were considered as BCM. The main outcomes were all-cause
      mortality and recovery of renal function by type of dialyzer. We further explored
      these outcomes according to the flux properties (high-flux or low-flux) of each
      of these dialyzers. A meta-analysis was conducted by combining data using a
      random-effects model. MAIN RESULTS: Nine studies were included in the primary
      analysis of mortality, with a total of 1062 patients. None of the pooled RR's
      reached statistical significance. The pooled relative risk (RR) for mortality was
      0.93 (95% confidence interval (CI) = 0.81 to 1.07). The overall RR for recovery
      of renal function, inclusive of 1038 patients from nine studies was 1.09 (95% CI
      0.90 to 1.31). The pooled RR for mortality by dialyzer flux property was 1.03
      (95% CI 0.82 to 1.30). The RR for recovery of renal function by flux property was
      0.85 (95% CI 0.55 to 1.31). A meta-analysis of mortality of kidney transplant
      recipients was not possible, but the analysis of recovery of renal function in
      this patient population was 1.09 (95% CI 0.91to 1.31). Results of sensitivity
      analyses did not differ significantly from the primary analyses. AUTHORS'
      CONCLUSIONS: There is no demonstrable clinical advantage to the use of BCM versus
      BICM in patients with ARF who require intermittent hemodialysis.

PMID- 15846750
TI  - Preoperative fasting for preventing perioperative complications in children.
AB  - BACKGROUND: Children, like adults, are required to fast before general
      anaesthesia with the aim of reducing the volume and acidity of their stomach
      contents. It is thought that fasting reduces the risk of regurgitation and
      aspiration of gastric contents during surgery. Recent developments have
      encouraged a shift from the standard 'nil-by-mouth-from-midnight' fasting policy
      to more relaxed regimens. Practice has been slow to change due to questions
      relating to the duration of a total fast, the type and amount of intake
      permitted. OBJECTIVES: To systematically assess the effects of different fasting
      regimens (duration, type and volume of permitted intake) and the impact on
      perioperative complications and patient wellbeing (aspiration, regurgitation,
      related morbidity, thirst, hunger, pain, comfort, behaviour, nausea and vomiting)
      in children. SEARCH STRATEGY: We searched Cochrane Wounds Group Specialised
      Register, the Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL,
      the National Research Register, relevant conference proceedings and article
      reference lists and contacted experts. SELECTION CRITERIA: Randomised and quasi
      randomised controlled trials of preoperative fasting regimens for children were
      identified. DATA COLLECTION AND ANALYSIS: Data extraction and trial quality
      assessment was conducted independently by two authors. Trial authors were
      contacted for additional information including adverse events. MAIN RESULTS:
      Forty-three randomised controlled comparisons (from 23 trials) involving 2350
      children considered to be at normal risk of regurgitation or aspiration during
      anaesthesia. Only one incidence of aspiration and regurgitation was reported.
      Children permitted fluids up to 120 minutes preoperatively were not found to
      experience higher gastric volumes or lower gastric pH values than those who
      fasted. The children permitted fluids were also less thirsty and hungry, better
      behaved and more comfortable than those who fasted. Clear fluids preoperatively
      did not result in a clinically important difference in the children's gastric
      volume or pH. Evidence relating to the preoperative intake of milk was sparse.
      The volume of fluid permitted during the preoperative period did not appear to
      impact on children's intraoperative gastric volume or pH contents. AUTHORS'
      CONCLUSIONS: There is no evidence that children who are not permitted oral fluids
      for more than six hours preoperatively benefit in terms of intraoperative gastric
      volume and pH over children permitted unlimited fluids up to two hours
      preoperatively. Children permitted fluids have a more comfortable preoperative
      experience in terms of thirst and hunger. This evidence applies only to children
      who are considered to be at normal risk of aspiration/regurgitation during
      anaesthesia.

PMID- 15846751
TI  - Addition of inhaled long-acting beta2-agonists to inhaled steroids as first line
      therapy for persistent asthma in steroid-naive adults.
AB  - BACKGROUND: Consensus statements recommend the addition of long-acting inhaled
      beta2-agonists only in asthmatic patients who are inadequately controlled on
      inhaled corticosteroids. OBJECTIVES: To compare the efficacy of initiating anti
      inflammatory therapy using the combination of inhaled corticosteroids and long
      acting beta2-agonists (ICS+LABA) as compared to inhaled corticosteroids alone
      (ICS alone) in steroid-naive children and adults with persistent asthma. SEARCH
      STRATEGY: We identified randomised controlled trials (RCTs) through electronic
      database searches (Cochrane Airways Group Specialised Register, Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and CINAHL) until April
      2004, bibliographies of identified RCTs and correspondence with manufacturers.
      SELECTION CRITERIA: RCTs comparing the combination of inhaled corticosteroids and
      long-acting beta2-agonists (ICS + LABA) to inhaled corticosteroids (ICS) alone in
      steroid-naive children and adults with asthma. DATA COLLECTION AND ANALYSIS:
      Studies were assessed independently by each reviewer for methodological quality
      and data extraction. Confirmation was obtained from the trialists when possible.
      The primary endpoint was rate of asthma exacerbations requiring systemic
      corticosteroids. Secondary endpoints included pulmonary function tests (PFTs),
      symptoms, use of other measures of asthma control, adverse events, and withdrawal
      rates. MAIN RESULTS: Eighteen trials met the inclusion criteria; nine (totaling
      1061 adults) contributed sufficient data to be analysed. Baseline forced
      expiratory volume in one minute (FEV1) was less than 80% predicted value in four
      trials and equal to or greater than 80% in five trials. The long-acting beta2
      agonists (LABA) formoterol (N=2) or salmeterol (N=7) were added to a dose of at
      least 800 microg/day of beclomethasone dipropionate (BDP) equivalent of inhaled
      corticosteroids (ICS) in three trials and to at least 400 microg/day in the six
      remaining trials. Treatment with ICS plus LABA was not associated with a lower
      risk of exacerbations requiring oral corticosteroids than ICS alone (relative
      risk (RR) 1.2; 95% confidence interval (CI) 0.8 to 1.9). FEV1 improved
      significantly with LABA (weighted mean difference (WMD) 210 ml; 95% CI 120 to
      300), as did symptom-free days (WMD 10.74%; 95% CI 1.86 to 19.62), but the change
      in use of rescue fast-acting beta2-agonists was not significantly different
      between the groups (WMD -0.4 puff/day, 95% CI -0.9 to 0.1). There was no
      significant group difference in adverse events (RR 1.1; 95% CI 0.8 to 1.5),
      withdrawals (RR 0.9; 95% CI 0.6 to 1.2), or withdrawals due to poor asthma
      control (RR 1.3; 95% CI 0.5 to 3.4). AUTHORS' CONCLUSIONS: In steroid-naive
      patients with mild to moderate airway obstruction, the initiation of inhaled
      corticosteroids in combination with long-acting beta2-agonists does not
      significantly reduce the rate of exacerbations over that achieved with inhaled
      corticosteroids alone; it does improve lung function and symptom-free days but
      does not reduce rescue beta2-agonist use as compared to inhaled steroids alone.
      Both options appear safe. There is insufficient evidence at present to recommend
      use of combination therapy rather than ICS alone as a first-line treatment.

PMID- 15846752
TI  - Primary stenting versus primary balloon angioplasty for treating acute myocardial
      infarction.
AB  - BACKGROUND: Balloon angioplasty following myocardial infarction (MI) reduces
      death, non-fatal MI and stroke compared to thrombolytic reperfusion. However up
      to 50% of patients experience restenosis and 3% to 5% recurrent myocardial
      infarction. Therefore, primary stenting may offer additional benefits compared to
      balloon angioplasty in patients with acute myocardial infarction. OBJECTIVES: To
      examine whether primary stenting compared to primary balloon angioplasty reduces
      clinical outcomes in patients with acute myocardial infarction. SEARCH STRATEGY:
      We searched MEDLINE, EMBASE, Pascal, Index medicus and The Cochrane Controlled
      Trials Register (The Cochrane Library) from 1979 to March 2002. SELECTION
      CRITERIA: Randomised controlled trials of primary stenting or balloon angioplasty
      prior to the invasive procedure; intervention in native coronary arteries within
      24 hours after onset of symptoms of myocardial infarction; report of death or
      reinfarction; and follow-up of at least 1 month. Trials were excluded when
      randomisation occurred after an invasive procedure and if they exclusively
      included patients with cardiogenic shock. DATA COLLECTION AND ANALYSIS: Two
      reviewers independently selected and extracted data from identified trials.
      Outcomes included mortality, reinfarction, coronary artery bypass grafting,
      target vessel revascularization, need for vascular repair or blood transfusion.
      Peto odds ratios were calculated. To explore the stability of the overall
      treatment effect various sensitivity analyses were performed. MAIN RESULTS: We
      included nine trials of 4433 participants. Odds ratios for mortality after
      stenting compared to balloon angioplasty at 30 days, 6 and 12 months were 1.16
      (95% CI 0.78 to 1.73), 1.27 (95% CI 0.89 to 1.83), and 1.06 (95% CI 0.77 to
      1.45). At 30 days, 6 and 12 months odds ratios for reinfarction after stenting
      compared to balloon angioplasty were 0.52 (95% CI 0.31 to 0.87), 0.67 (95% CI
      0.45 to 1.00), and 0.67 (95% CI 0.45-0.98) and odds ratio for target vessel
      revascularization after stenting compared to balloon angioplasty were 0.45 (95%CI
      0.34 to 0.60), 0.42 (95% CI 0.35 to 0.51), and 0.47 (95% CI 0.38 to 0.57). The
      odds ratio for post-interventional bleeding complications after stenting compared
      to balloon angioplasty was 1.34 (95% CI 0.95 to 1.88; test of heterogeneity p >
      0.1). AUTHORS' CONCLUSIONS: There is no evidence to suggest that primary stenting
      reduces mortality when compared to balloon angioplasty. Stenting seems to be
      associated with a reduced risk of reinfarction and target vessel
      revascularization, but potential confounding due to unbalanced post
      interventional antithrombotic/anticoagulant therapies can not be ruled out on
      basis of this review.

PMID- 15846753
TI  - Acupuncture for shoulder pain.
AB  - BACKGROUND: There are many commonly employed forms of treatment for shoulder
      disorders. This review of acupuncture is one in a series of reviews of varying
      interventions for shoulder disorders including adhesive capsulitis (frozen
      shoulder), rotator cuff disease and osteoarthritis. Acupuncture to treat
      musculoskeletal pain is being used increasingly to confer an analgesic effect and
      to date its use in shoulder disorder has not been evaluated in a systematic
      review. OBJECTIVES: To determine the efficacy and safety of acupuncture in the
      treatment of adults with shoulder pain. SEARCH STRATEGY: The Cochrane Controlled
      Trials Register, MEDLINE, EMBASE and CINAHL were searched from inception to
      December 2003, and reference lists from relevant trials were reviewed. SELECTION
      CRITERIA: Randomised and quasi-randomised trials, in all languages, of
      acupuncture compared to placebo or another intervention in adults with shoulder
      pain. Specific exclusions were duration of shoulder pain less than three weeks,
      rheumatoid arthritis, polymyalgia rheumatica, cervically referred pain and
      fracture. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted
      trial and outcome data. For continuous outcome measures where the standard
      deviations were not reported it was either calculated from the raw data or
      converted from the standard error of the mean. If neither of these was reported,
      authors were contacted. Where results were reported as median and range, the
      trial was not included in the meta-analysis, but presented in Additional Tables.
      Effect sizes were calculated and combined in a pooled analysis if the study end
      points population and intervention were homogenous. Results are presented
      separately for rotator cuff disease, adhesive capsulitis, full thickness rotator
      cuff tear and mixed diagnoses, and, where possible, combined in meta-analysis to
      indicate effect of acupuncture across all shoulder disorders. MAIN RESULTS: Nine
      trials of varying methodological quality met the inclusion criteria. For all
      trials there was poor description of interventions. Varying placebos were used in
      the different trials. Two trials assessed short-term success (post intervention)
      of acupuncture for rotator cuff disease and could be combined in meta analysis.
      There was no significant difference in short-term improvement associated with
      acupuncture when compared to placebo, but due to small sample sizes this may be
      explained by Type II error. Acupuncture was of benefit over placebo in improving
      the Constant Murley Score (a measure of shoulder function) at four weeks (WMD
      17.3 (7.79, 26.81)). However, by four months, the difference between the
      acupuncture and placebo groups, whilst still statistically significant, was no
      longer likely to be clinically significant (WMD 3.53 (0.74, 6.32)). The Constant
      Murley Score is graded out of 100, hence a change of 3.53 is unlikely to be of
      substantial benefit. The results of a small pilot study demonstrated some benefit
      of both traditional and ear acupuncture plus mobilization over mobilization
      alone. There was no difference in adverse events related to acupuncture when
      compared to placebo, however this was assessed by only one trial AUTHORS'
      CONCLUSIONS: Due to a small number of clinical and methodologically diverse
      trials, little can be concluded from this review. There is little evidence to
      support or refute the use of acupuncture for shoulder pain although there may be
      short-term benefit with respect to pain and function. There is a need for further
      well designed clinical trials.

PMID- 15846754
TI  - Viscosupplementation for the treatment of osteoarthritis of the knee.
AB  - BACKGROUND: Osteoarthritis (OA) is the most prevalent chronic joint disorder
      worldwide and is associated with significant pain and disability. OBJECTIVES: To
      assess the effects of viscosupplementation in the treatment of OA of the knee.
      The products were hyaluronan and hylan derivatives (Adant, Arthrum H, Artz
      (Artzal, Supartz), BioHy (Arthrease), Durolane, Fermathron, Go-On, Hyalgan, Hylan
      G-F 20 (Synvisc Hylan G-F 20), NRD-101, Orthovisc, Ostenil, Replasyn, SLM-10,
      Suplasyn, Synject and Zeel compositum). SEARCH STRATEGY: MEDLINE, EMBASE,
      PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register
      of Controlled Trials (CENTRAL) were searched. Specialised journals and reference
      lists of identified randomised controlled trials (RCTs) and pertinent review
      articles up to April 2004 were handsearched. SELECTION CRITERIA: RCTs of
      viscosupplementation for the treatment of people with a diagnosis of OA of the
      knee were eligible. Single and double-blinded studies, placebo-based and
      comparative studies were eligible. At least one of the four OMERACT III core set
      outcome measures had to be reported (Bellamy 1997). DATA COLLECTION AND ANALYSIS:
      Each trial was assessed independently by two reviewers (NB, JC) for its
      methodological quality using a validated tool. All data were extracted by one
      reviewer (JC) and verified by a second reviewer (VR). Continuous outcome measures
      were analysed as weighted mean differences (WMD) with 95% confidence intervals
      (CI). Dichotomous outcomes were analyzed by relative risk (RR). MAIN RESULTS:
      Sixty-three trials with a median quality score of 3 (range 1 to 5) were
      identified. Follow-up periods varied between day of last injection and one year.
      Thirty-seven trials included comparisons of hyaluronan/hylan and placebo, nine
      trials included comparisons of intra-articular (IA) corticosteroids, and five
      trials included comparisons of nonsteroidal anti-inflammatory drugs (NSAIDs). The
      pooled analyses of the effects of viscosupplements against 'placebo' controls
      generally supported the efficacy of this class of intervention. In these same
      analyses, differential efficacy effects were observed for different products on
      different variables and at different timepoints. Of note is the 5 to 13 week post
      injection period which showed a percent improvement from baseline of 11 to 54%
      for pain and 9 to 15% for function. In general, comparable efficacy was noted
      against NSAIDs and longer-term benefits were noted in comparisons against IA
      corticosteroids. In general, few adverse events were reported in the
      hyaluronan/hylan trials included in these analyses. AUTHORS' CONCLUSIONS: Based
      on the aforementioned analyses, viscosupplementation is an effective treatment
      for OA of the knee with beneficial effects: on pain, function and patient global
      assessment; and at different post injection periods but especially at the 5 to 13
      week post injection period. It is of note that based on non-randomised groups,
      the magnitude of the clinical effect, as expressed by the WMD and standardised
      mean difference (SMD) from the RevMan 4.1 output, is different for different
      products, comparisons, timepoints, variables and trial designs. However, there
      are few randomised head-to-head comparisons of different viscosupplements and
      readers should be cautious, therefore, in drawing conclusions regarding the
      relative value of different products. The clinical effect for some products,
      against placebo, on some variables at some timepoints is in the moderate to large
      effect-size range. Readers should refer to relevant tables to review specific
      detail given the heterogeneity in effects across the product class and some
      discrepancies observed between the RevMan 4.1 analyses and the original
      publications. Overall, the analyses performed are positive for the HA class and
      particularly positive for some products with respect to certain variables and
      timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection. In
      general, sample-size restrictions preclude any definitive comment on the safety
      of the HA class of products; however, within the constraints of the trial designs
      employed no major safety issues were detected. In some analyses viscosupplements
      were comparable in efficacy to systemic forms of active intervention, with more
      local reactions but fewer systemic adverse events. In other analyses HA products
      had more prolonged effects than IA corticosteroids. Overall, the aforementioned
      analyses support the use of the HA class of products in the treatment of knee OA.

PMID- 15846755
TI  - Intraarticular corticosteroid for treatment of osteoarthritis of the knee.
AB  - BACKGROUND: Osteoarthritis (OA) is a common joint disorder. In the knee,
      injections of corticosteroids into the joint (intra-articular (IA)) may relieve
      inflammation, and reduce pain and disability. OBJECTIVES: To evaluate the
      efficacy and safety of IA corticosteroids in treatment of OA of the knee. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials
      (CENTRAL) (Issue 2, 2003), MEDLINE, EMBASE, PREMEDLINE (all to July 2003), and
      Current Contents (Sept 2000). Specialised journals, trial reference lists and
      review articles were handsearched. SELECTION CRITERIA: Randomised controlled
      trials of IA corticosteroids for patients with OA of the knee: single/double
      blind, placebo-based/comparative studies, reporting at least one core OMERACT III
      outcome measure. DATA COLLECTION AND ANALYSIS: Methodological quality of trials
      was assessed, and data were extracted in duplicate. Fixed effect and random
      effects models, giving weighted mean differences (WMD), were used for continuous
      variables. Dichotomous outcomes were analysed by relative risk (RR). MAIN
      RESULTS: Twenty-six trials (1721 participants) comparing IA corticosteroid
      against placebo, against IA hyaluronan/hylan (HA products), against joint lavage,
      and against other IA corticosteroids, were included.IA corticosteroid was more
      effective than IA placebo for pain reduction (WMD -17.79; 95% confidence interval
      (CI) -25.02 to -10.55) and patient global assessment (the RR was 1.44 (95% CI
      1.13 to 1.82)) at one week post injection with an NNT of 3 to 4 for both, based
      on n=185 for pain on 100 mm visual analogue scale (VAS) and n=158 for patient
      global assessment. Data on function were sparse at one week post injection and
      neither statistically significant nor clinically important differences were
      detected. There was evidence of pain reduction between two weeks (the RR was 1.81
      (95% CI 1.09 to 3.00)) to three weeks (the RR was 3.11 (95% CI 1.61 to 6.01), but
      a lack of evidence for efficacy in functional improvement. At four to 24 weeks
      post injection, there was lack of evidence of effect on pain and function (small
      studies showed benefits which did not reach statistical or clinical importance,
      i.e. less than 20% risk difference). For patient global, there were three studies
      which consistently showed lack of effect longer than one week post injection.
      However, all were fairly small sample sizes (less than 50 patients per group).
      This was supported by another study which did not find statistically significant
      differences, at any time point, on a continuous measure of patient global
      assessment (100 mm VAS). In comparisons of corticosteroids and HA products, no
      statistically significant differences were in general detected at one to four
      weeks post injection. Between five and 13 weeks post injection, HA products were
      more effective than corticosteroids for one or more of the following variables:
      WOMAC OA Index, Lequesne Index, pain, range of motion (flexion), and number of
      responders. One study showed a difference in function between 14 to 26 weeks, but
      no differences in efficacy were detected at 45 to 52 weeks. In general, the onset
      of effect was similar with IA corticosteroids, but was less durable than with HA
      products. Comparisons of IA corticosteroids showed triamcinolone hexacetonide was
      superior to betamethasone for number of patients reporting pain reduction up to
      four weeks post injection (the RR was 2.00 (95% CI 1.10 to 3.63). Comparisons
      between IA corticosteroid and joint lavage showed no differences in any of the
      efficacy or safety outcome measures. AUTHORS' CONCLUSIONS: The short-term benefit
      of IA corticosteroids in treatment of knee OA is well established, and few side
      effects have been reported. Longer term benefits have not been confirmed based on
      the RevMan analysis. The response to HA products appears more durable. In this
      review, some discrepancies were observed between the RevMan 4.1 analysis and the
      original publication. These are likely the result of using secondary rather than
      primary data and the statistical methods available in RevMan 4.1. Future trials
      should have standardised outcome measures and assessment times, run longer,
      investigate different patient subgroups, and clinical predictors of response
      (those associated with inflammation and structural damage).

PMID- 15846756
TI  - The diagnosis of gestational trophoblastic disease in early pregnancy:
      implications for screening, counseling and management.

PMID- 15846757
TI  - Effects of ultrasound on maternal-fetal bonding: a comparison of two- and three
      dimensional imaging.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of two
      dimensional (2DUS) compared to three-dimensional ultrasound (3DUS) imaging on the
      maternal-fetal bonding process. METHODS: Fifty mothers who had 2DUS and 50 who
      had 2DUS and 3DUS were included in the study. A postpartum survey by telephone
      interview was carried out to assess maternal-fetal bonding. Bonding was evaluated
      by analysis of extent of prenatal image sharing, maternal ability to form a
      mental picture of the baby and mother's comments about their ultrasound images.
      Data were analyzed using the independent t-test, Chi-square and Mann-Whitney U
      tests. RESULTS: Mothers who received 3DUS showed their ultrasound images to more
      people (median, 27.5; interquartile range, 14.5-40.0) than mothers receiving 2DUS
      alone (median, 11.0; interquartile range, 5.0-25.5) (P < 0.001, Z = -3.539).
      Eighty-two percent of the subjects screened with 3DUS had a greater tendency to
      form a mental picture of the baby postexamination compared to 39% of the 2DUS
      subjects (P < 0.001, Z = -3.614). Mothers receiving a 3DUS study were more likely
      to receive comments on the similarities/differences of the neonate compared to
      those having 2DUS studies. Furthermore, 70% of the mothers receiving 3DUS felt
      they 'knew' the baby immediately after birth vs. 56% of the mothers receiving
      2DUS (P = 0.009, Z = -2.613). Both 2DUS and 3DUS experiences were positive,
      however, the comments made by the mothers undergoing 3DUS (n = 18) were more
      exclamatory (amazed, wonderful, fabulous) than those undergoing 2DUS (n = 4).
      Patients having a 3DUS examination consistently scored higher than those having a
      2DUS examination alone for all categories of maternal-fetal bonding. CONCLUSION:
      3DUS appears to more positively influence the perceptions of mothers to their
      babies postbirth compared to 2DUS. Specifically, mothers who had 3DUS showed
      their ultrasound images to a greater number of people compared to mothers who had
      2DUS alone and this may represent mother's social support system. 3DUS may have a
      greater impact on the maternal-fetal bonding process.

PMID- 15846758
TI  - Luteal dynamics during the human menstrual cycle: new insight from imaging.

PMID- 15846759
TI  - Outcome of fetal renal pelvic dilatation diagnosed during the third trimester.
AB  - OBJECTIVES: The aim of this study was to evaluate renal function and the need for
      postnatal treatment--antibiotic therapy and/or surgery--in relation to the grade
      of fetal renal pelvic dilatation (RPD) found on third-trimester ultrasound
      examination. METHODS: The retrospective study included 78 children, born between
      1995 and 2000, with 115 dilated fetal renal pelvic units. The children were
      allocated to three groups based on pelvic anteroposterior diameter (APD) detected
      on third-trimester ultrasound: APDs of 7-9.9 mm, 10-14.9 mm and > or = 15 mm were
      classified as mild dilatation, moderate hydronephrosis and severe hydronephrosis,
      respectively. Renal function was assessed by scintigraphy. RESULTS: None of the
      20 children with mild dilatation experienced a urinary tract infection (UTI) or
      underwent surgery; two had associated renal or urinary tract abnormalities. In
      contrast, five out of 22 (23%) children with moderate hydronephrosis and 23 out
      of 36 (64%) with severe hydronephrosis had either a UTI or required surgery (P <
      0.001); associated abnormalities were also more common (6 out of 22 and 15 out of
      36, respectively). There was no significant correlation between the grade of
      antenatal RPD and postnatal ipsilateral renal function. CONCLUSIONS: The need for
      postnatal treatment increased significantly with the grade of antenatal RPD.
      Children with antenatal mild dilatation were discharged early from follow-up
      whereas those with moderate and severe fetal hydronephrosis needed close follow
      up by a multidisciplinary team.

PMID- 15846761
TI  - A novel method to improve prenatal diagnosis of abnormal systemic venous
      connections using three- and four-dimensional ultrasonography and 'inversion
      mode'.
AB  - OBJECTIVE: The precise prenatal diagnosis of abnormal venous connections of the
      fetal heart is challenging. Anatomical accuracy may be important in determining
      the best route for postnatal angiography, as well as the prognosis and treatment.
      This study was designed to determine the value of 'inversion mode', a new three-
      and four-dimensional (4D) rendering algorithm, in the visualization of the
      spatial relationships of an interrupted inferior vena cava (IVC) with azygos or
      hemiazygos vein continuation associated with and without heterotaxic syndromes.
      METHODS: Heart volumes were acquired using 4D ultrasonography and spatiotemporal
      image correlation in cases of interrupted IVC with azygos/hemiazygos continuation
      (n = 3). Volume datasets were rendered using the 'inversion mode' algorithm and
      abnormal images were compared to those generated from a library of normal
      fetuses. RESULTS: The 'inversion mode' rendering algorithm allowed the
      visualization of dilated azygos or hemiazygos veins and their spatial
      relationships with the descending aorta, the aortic arch, the superior vena cava,
      and the atria in cases of interrupted IVC with and without heterotaxic syndromes.
      CONCLUSIONS: The 'inversion mode' algorithm improves prenatal visualization of
      both dilated azygos and hemiazygos veins, as well as their spatial relationships
      with the surrounding vascular structures. This has implications for the accurate
      prenatal diagnosis and management of neonates with abnormal systemic venous
      connections.

PMID- 15846762
TI  - Form and function of the corpus luteum during the human menstrual cycle.
AB  - OBJECTIVE: To characterize the growth and regression of the corpus luteum (CL)
      during an interovulatory interval (IOI) using serial transvaginal
      ultrasonography. METHODS: Fifty healthy women of reproductive age with a history
      of regular menstrual cycles underwent daily transvaginal ultrasonography for one
      IOI. Measurements of luteal area and luteal numerical pixel value (NPV) were
      recorded each day after ovulation until the CL could no longer be detected. Blood
      was drawn every third day during the IOI to measure serum concentrations of
      progesterone and estradiol-17beta. RESULTS: Corpora lutea were of two
      morphological types: those with a central fluid-filled cavity (CFFC) (78%) and
      those without (22%). Eighty-eight percent of women exhibited a CL containing a
      CFFC 2 days after ovulation, followed by 34% 13 days after ovulation and 2% 27
      days after ovulation. Luteal area, progesterone concentration and estradiol
      concentration increased for approximately the first 6 days following ovulation
      followed by a subsequent decline. Luteal NPV decreased from days 1 to 11 and
      increased during days 11-16. Changes in luteal area, NPV, progesterone and
      estradiol concentrations did not differ in women with two versus three waves of
      follicular development. CONCLUSIONS: Peak luteal function, as determined by
      maximum luteal area, progesterone concentration and estradiol concentration, is
      observed 6 days following ovulation. Luteal NPV is reflective of morphological
      and endocrinological changes in the CL. The development of a CFFC during
      luteinization is a normal physiological phenomenon. The CL can be detected, but
      is not functional, during the follicular phase of the menstrual cycle.

PMID- 15846763
TI  - Power Doppler vascularity index for predicting malignancy of adnexal masses.
AB  - OBJECTIVE: To assess the performance of a power Doppler vascularity index in the
      preoperative diagnosis of ovarian malignancy. METHODS: Adnexal masses (n = 101)
      were examined prospectively with power Doppler ultrasonography before surgical
      treatment. The tumor vascularity index (power Doppler index, PDI) was determined
      by quantification of the number of pixels in a defined region of interest
      according to the formula: number of colored pixels/(total number of pixels minus
      the number of pixels in the fluid or avascular areas). It was estimated on
      selected frames of the tumors using an in-house color-quantifying program added
      to MATLAB 6.0 software. Inter- and intraobserver reproducibilities of PDI
      assessment were evaluated. Intratumoral blood flow velocity waveforms were
      obtained to determine the lowest resistance index (RI). A subjective visual score
      of power Doppler signals in the tumor was used to classify it as having low,
      moderate or high vascularity. The discriminatory ability of this score was
      compared to that of RI and PDI measurement. RESULTS: Histology identified 23
      malignant and 78 benign lesions. The PDI was considerably higher in malignant
      than in benign lesions (0.34 +/- 0.04 vs. 0.12 +/- 0.06; P < 0.001). The intra-
      and interobserver variabilities of PDI were low (intraclass correlation
      coefficients of 0.99 and 0.97, respectively). The PDI cut-off value to
      differentiate malignant from benign tumors was set at 0.265 (26.5% of the tumor
      being colored). Using this cut-off, sensitivity and specificity were 100% (95%
      CI, 87.8-100.0) and 97.4% (95% CI, 91.0-99.7) compared to 78.3% (95% CI, 56.3
      92.5) and 83.1% (95% CI, 72.9-90.7) for RI (cut-off value of 0.53) and 78.3% (95%
      CI, 56.3-92.5) and 94.9% (95% CI, 87.4-98.6) for visual scoring. Logistic
      regression demonstrated that PDI was the best parameter for differentiating
      between malignant and benign tumors. CONCLUSION: The power Doppler vascularity
      index obtained using customized color quantifying software has high diagnostic
      value in discriminating between benign and malignant adnexal masses.

PMID- 15846764
TI  - Two- and three-dimensional sonographic findings in a case of distal urethral
      obstruction due to a paraurethral tumor.
AB  - The cause of bladder outlet obstruction in women may be categorized generally
      into two types, functional and anatomical. On ultrasonography, the urethra
      appears as a tubular structure with a central echolucent part and surrounding
      hyperechogenic structures. Morphological changes in the echolucent portion of the
      urethra have been reported to be associated with voiding dysfunction. We present
      a case of distal urethral obstruction secondary to metastatic paraurethral
      adenocarcinoma. Three-dimensional sonography clearly demonstrated the
      configuration of the metastatic tumor and its spatial orientation in association
      with distal urethral obstruction.

PMID- 15846765
TI  - Antenatal diagnosis of fetal renal calculus.
AB  - Pediatric urolithiasis is commonly associated with structural renal tract
      anomalies and metabolic disorders. Antenatal diagnosis of renal calculi is
      extremely rare, with only one report in the literature. We present a case of
      renal stone formation diagnosed at 34 weeks' gestation on ultrasound examination.

PMID- 15846766
TI  - Intrauterine diagnosis and treatment of a concordant complete heart block in a
      twin pregnancy.

PMID- 15846767
TI  - Increased uterine artery vascular impedance is related to adverse outcome of
      pregnancy but is present in only one-third of late third-trimester pre-eclamptic
      women.
AB  - OBJECTIVE: Signs of increased uterine artery vascular impedance in mid-gestation
      are strongly related to pre-eclampsia later in pregnancy. Whether this is true
      for the late third trimester is, however, unclear. The aim of the present study
      was to analyze the frequency of increased uterine artery vascular impedance in
      the third trimester, and its relationship to abnormal umbilical artery Doppler
      and adverse outcome of pregnancy. METHODS: This was a retrospective study of
      uterine and umbilical artery Doppler velocimetry in 570 pregnancies complicated
      by pre-eclampsia. The managing clinician was informed only about the umbilical
      artery flow. The Doppler recordings were related to severity of pre-eclampsia,
      prematurity, fetal growth restriction, and rates of Cesarean section and
      admission to neonatal intensive care. RESULTS: Increased umbilical artery
      vascular impedance was seen in 59 cases (10.4%), seven having absent or reversed
      end-diastolic flow. Uterine artery notching was seen in 145 cases (25%), 88 (15%)
      having bilateral notches. Either increased uterine artery pulsatility index (PI)
      or notching, or both, were seen in 207 women (36.3%). In 108 women with severe
      pre-eclampsia, 38 (35.2%) had uterine artery notching. Signs of increased
      uteroplacental vascular impedance were more common in severe than in mild pre
      eclampsia (57.4% vs. 31.4%), in premature than in term pregnancies (70.9% vs.
      28.4%), and were more prevalent than abnormality in the umbilical artery (36.3%
      vs. 10.4%). CONCLUSION: Only one-third of pre-eclamptic cases showed signs of
      increased uterine artery vascular impedance in the third trimester. However,
      signs of increased vascular impedance were much more frequent in the uterine than
      in the umbilical arteries and were strongly related to adverse outcome of
      pregnancy.

PMID- 15846768
TI  - Antenatal sonographic and magnetic resonance images of a giant hemangioma of the
      fetal skull.

PMID- 15846769
TI  - Differential activity in left inferior frontal gyrus for pseudowords and real
      words: an event-related fMRI study on auditory lexical decision.
AB  - After Newman and Twieg and others, we used a fast event-related functional
      magnetic resonance imaging (fMRI) design and contrasted the lexical processing of
      pseudowords and real words. Participants carried out an auditory lexical decision
      task on a list of randomly intermixed real and pseudo Chinese two-character (or
      two-syllable) words. The pseudowords were constructed by recombining constituent
      characters of the real words to control for sublexical code properties.
      Processing of pseudowords and real words activated a highly comparable network of
      brain regions, including bilateral inferior frontal gyrus, superior, middle
      temporal gyrus, calcarine and lingual gyrus, and left supramarginal gyrus.
      Mirroring a behavioral lexical effect, left inferior frontal gyrus (IFG) was
      significantly more activated for pseudowords than for real words. This result
      disconfirms a popular view that this area plays a role in grapheme-to-phoneme
      conversion, as such a conversion process was unnecessary in our task with
      auditory stimulus presentation. An alternative view was supported that attributes
      increased activity in left IFG for pseudowords to general processes in decision
      making, specifically in making positive versus negative responses. Activation in
      left supramarginal gyrus was of a much larger volume for real words than for
      pseudowords, suggesting a role of this region in the representation of
      phonological or semantic information for two-character Chinese words at the
      lexical level.

PMID- 15846770
TI  - Automated quality assurance routines for fMRI data applied to a multicenter
      study.
AB  - Standard procedures to achieve quality assessment (QA) of functional magnetic
      resonance imaging (fMRI) data are of great importance. A standardized and fully
      automated procedure for QA is presented that allows for classification of data
      quality and the detection of artifacts by inspecting temporal variations. The
      application of the procedure on phantom measurements was used to check scanner
      and stimulation hardware performance. In vivo imaging data were checked
      efficiently for artifacts within the standard fMRI post-processing procedure by
      realignment. Standardized and routinely carried out QA is essential for extensive
      data amounts as collected in fMRI, especially in multicenter studies.
      Furthermore, for the comparison of two different groups, it is important to
      ensure that data quality is approximately equal to avoid possible
      misinterpretations. This is shown by example, and criteria to quantify
      differences of data quality between two groups are defined.

PMID- 15846771
TI  - A new approach to neuroimaging with magnetoencephalography.
AB  - We discuss the application of beamforming techniques to the field of
      magnetoencephalography (MEG). We argue that beamformers have given us an insight
      into the dynamics of oscillatory changes across the cortex not explored
      previously with traditional analysis techniques that rely on averaged evoked
      responses. We review several experiments that have used beamformers, with special
      emphasis on those in which the results have been compared to those observed in
      functional magnetic resonance imaging (fMRI) and on those studying induced
      phenomena. We suggest that the success of the beamformer technique, despite the
      assumption that there are no linear interactions between the mesoscopic local
      field potentials across distinct cortical areas, may tell us something of the
      balance between functional integration and segregation in the human brain. What
      is more, MEG beamformer analysis facilitates the study of these complex
      interactions within cortical networks that are involved in both sensory-motor and
      cognitive processes.

PMID- 15846772
TI  - Voxel-based analysis of MRI detects abnormal visual cortex in children and adults
      with amblyopia.
AB  - Amblyopia, sometimes called "lazy eye," is a relatively common developmental
      visual disorder well characterized behaviorally; however, the neural substrates
      associated with amblyopia in humans remain unclear. We hypothesized that
      abnormalities in the cerebral cortex of subjects with amblyopia exist, possibly
      as a result of experience-dependent neuronal plasticity. Anatomic magnetic
      resonance imaging (MRI) and psychophysical vision testing was carried out on 74
      subjects divided into two age ranges, 7-12 years and 18-35 years, and three
      diagnoses, strabismic amblyopia, anisometropic amblyopia, and normal vision. We
      report a behavioral impairment in contrast sensitivity for subjects with
      amblyopia, consistent with previous reports. When the high-resolution MRI brain
      images were analyzed quantitatively with optimized voxel-based morphometry,
      results indicated that adults and children with amblyopia have decreased gray
      matter volume in visual cortical regions, including the calcarine sulcus, known
      to contain primary visual cortex. This finding was confirmed with a separate
      region-of-interest analysis. For the children with amblyopia, additional gray
      matter reductions in parietal-occipital areas and ventral temporal cortex were
      detected, consistent with recent reports that amblyopia can result in spatial
      location and object processing deficits. These data are the first to provide
      possible neuroanatomic bases for the loss of binocularity and visual sensitivity
      in children and adults with amblyopia.

PMID- 15846773
TI  - A novel 3D hepatectomy simulation based on liver circulation: application to
      liver resection and transplantation.
AB  - Hepatectomy is a complicated operative procedure because of its anatomical
      complexity, vascular variability, and impaired hepatic function due to associated
      hepatitis or cirrhosis. Thus preoperative detailed topography and precise liver
      resection volume measurements should be obtained for a curative hepatectomy. The
      aim of this study was to assess the feasibility and accuracy of a novel three
      dimensional (3D) virtual hepatectomy simulation software in patients who
      underwent liver resection or living donor liver transplantation. We developed the
      hepatectomy simulation software, which was programmed to analyze detailed 3D
      vascular structure and to predict liver resection volume and margins. In 72
      patients receiving hepatectomy, the predicted liver resection volumes and margins
      revealed a significant correlation with the actual value with a mean difference
      of 9.3 mL (P < .0001) and 1.6 mm (P < .01), respectively. The drainage area by
      hepatic veins was quantified to achieve reconstruction of the corresponding
      venous branch. In conclusion, this hepatectomy simulation software reliably
      predicted an accurate liver resection volume, the cancer-free margin, and the
      drainage volume of hepatic vein branches. This software may promote curative
      hepatectomy and may be used for other interventional therapies in the treatment
      of liver disease.

PMID- 15846774
TI  - Isolation and antifungal activity of kakuol, a propiophenone derivative from
      Asarum sieboldii rhizome.
AB  - An antifungal substance active against Colletotrichum orbiculare (Berk & Mont)
      Arx was isolated from the methanol extracts of Asarum sieboldii (Miq) Maek
      rhizomes. High-resolution MS, NMR and UV spectral data confirmed that the
      antifungal substance is kakuol, 2-hydroxy-4,5-methylenedioxypropiophenone.
      Colletotrichum orbiculare was most sensitive to kakuol, with MIC of 10 microg ml(
      1). Kakuol also completely inhibited the mycelial growth of Botrytis cinerea Pers
      ex Fr and Cladosporium cucumerinum Ellis & Arthur at 50 microg ml(-1) and 30
      microg ml(-1), respectively. However, no antimicrobial activity was found against
      yeast and bacteria even at 100 microg ml(-1). Kakuol exhibited a protective
      activity against the development of anthracnose disease on cucumber plants. The
      control efficacy of kakuol against the anthracnose disease was in general
      somewhat less than that of the commercial fungicide chlorothalonil. This is the
      first report to demonstrate in vitro and in vivo antifungal activity of kakuol
      against C. orbiculare infection.

PMID- 15846775
TI  - Assessment by M-FISH of karyotypic complexity and cytogenetic evolution in
      bladder cancer in vitro.
AB  - We carried out multiplex fluorescence in situ hybridization (M-FISH) and follow
      up FISH studies on a large series of transitional cell carcinoma (TCC) cell lines
      and 2 normal urothelium-derived cell lines, several of which have not had
      karyotypes reported previously. M-FISH analysis, with appropriate follow-up,
      complements conventional cytogenetic analysis and array CGH studies, allowing a
      more accurate definition of karyotype. The detailed karyotypic data obtained will
      assist in choosing suitable cell lines for functional studies and identifies
      common losses, gains, breakpoints and potential fusion gene sites in TCC. We have
      shown changes in cell lines RT112 and DSH1 following prolonged culture, and
      differences in karyotype, between RT112 cultures obtained from different sources.
      We propose a model for the evolutionary changes leading to these differences. A
      comparison with the literature found other examples of differences in cell-line
      karyotypes between different sources. Nevertheless, several karyotypic changes
      were preserved between different sources of the same cell line and were also seen
      in more than one cell line. These may be the most important changes and include 
      8p, +20, 4q-, 10p-, 16p- and breaks in 8p21. We carried out a more detailed
      follow-up of some regions, which showed involvement of 8p breaks and losses in 15
      of 16 TCC cell lines but in neither of the normal urothelium-derived cell lines.
      Some changes represented distal loss, whereas others were small deletions.
      Further study of this region is warranted.

PMID- 15846776
TI  - Differences in nuclear positioning of 1q12 pericentric heterochromatin in normal
      and tumor B lymphocytes with 1q rearrangements.
AB  - The frequent rearrangement of chromosome band 1q12 constitutive heterochromatin
      in hematologic malignancies suggests that this rearrangement plays an important
      pathogenetic role in these diseases. The oncogenic mechanisms linked to 1q12
      heterochromatin are unknown. Constitutive heterochromatin can epigenetically
      regulate gene function through the formation of transcriptional-silencing
      compartments. Thus, as a first step toward understanding whether 1q12
      rearrangements might compromise such activity in tumor cells, we investigated the
      3-D organization of the 1q12 heterochromatin domain (1q12HcD) in normal and tumor
      B lymphocytes. Strikingly, in normal B cells, we showed that the 1q12HcD
      dynamically organizes to the nuclear periphery in response to B-cell receptor
      engagement. Specifically, we observed an almost twofold increase in 1q12Hc
      domains at the extreme nuclear periphery in activated versus resting B
      lymphocytes. Remarkably, 1q12Hc organization was noticeably altered in tumor
      cells that showed structural alterations of 1q12; the 1q12Hc domains were
      significantly displaced from the extreme nuclear periphery compared to normal
      activated B lymphocytes (P > 0.0001), although overall peripheral localization
      was maintained. In a case in which there was a translocation of IGL enhancer to
      1q, the altered nuclear positioning of the 1q12HcD was even more pronounced (5%
      of the 1q12Hc domains at the nuclear periphery compared to 20% in other lymphoma
      lines), and we were able to mimic this effect in two additional B-cell tumor
      lines by treatment with trichostatin A, a histone deacetylase (HDAC) inhibitor.
      Taken together, these results point to the 1q12HcD having a specific, nonrandom,
      and regulated peripheral organization in B lymphocytes. This organization is
      significantly disrupted in lymphoma cells harboring 1q rearrangements.

PMID- 15846777
TI  - Insulin-like growth factor-I protects granule neurons from apoptosis and improves
      ataxia in weaver mice.
AB  - Most cerebellar granule neurons in weaver mice undergo premature apoptosis during
      the first 3 postnatal weeks, subsequently leading to severe ataxia. The death of
      these granule neurons appears to result from a point mutation in the GIRK2 gene,
      which encodes a G protein-activated, inwardly rectifying K+ channel protein.
      Although the genetic defect was identified, the molecular mechanism by which the
      mutant K+ channel selectively attacks granule neurons in weaver mice is unclear.
      Before their demise, weaver granule neurons express abnormally high levels of
      insulin-like growth factor (IGF) binding protein 5 (IGFBP5). IGF-I is essential
      for the survival of cerebellar neurons during their differentiation. Because
      IGFBP5 has the capacity to block IGF-I activity, we hypothesized that reduced IGF
      I availability resulting from excess IGFBP5 accelerates the apoptosis of weaver
      granule neurons. We found that, consistently with this hypothesis, exogenous IGF
      I partially protected cultured weaver granule neurons from apoptosis by
      activating Akt and decreasing caspase-3 activity. To determine whether IGF-I
      protects granule neurons in vivo, we cross-bred weaver mice with transgenic mice
      that overexpress IGF-I in the cerebellum. The cerebellar volume was increased in
      weaver mice carrying the IGF-I transgene, predominantly because of an increased
      number of surviving granule neurons. The presence of the IGF-I transgene resulted
      in improved muscle strength and a reduction in ataxia, indicating that the
      surviving granule neurons are functionally integrated into the cerebellar
      neuronal circuitry. These results confirm our previous suggestion that a lack of
      IGF-I activity contributes to apoptosis of weaver granule neurons in vivo and
      supports IGF-I's potential therapeutic use in neurodegenerative disease.

PMID- 15846778
TI  - Transcriptome analysis of frontal cortex in alcohol-preferring and nonpreferring
      rats.
AB  - Although it is widely accepted that alcohol abuse and alcoholism have a
      significant genetic component of risk, the identities of the genes themselves
      remain obscure. To illuminate such potential genetic contributions, DNA
      macroarrays were used to probe for differences in normative cortical gene
      expression between rat strains genetically selected for alcohol self
      administration preference, AA (Alko, alcohol) and P (Indiana, preferring), or
      avoidance, ANA (Alko, nonalcohol) and NP (Indiana, nonpreferring). Among 1,176
      genes studied, six demonstrated confirmable, differential expression following
      comparison of ethanol-naive AA and ANA rats. Specifically, the mRNA level for
      metabotropic glutamate receptor 3 (mGluR3) was down-regulated in the AA vs. ANA
      lines. In contrast, calcium channel subunit alpha2delta1 (cacna2d1), vesicle
      associated membrane protein 2 (VAMP2), syntaxin 1 (both syntaxin 1a and 1b; STX1a
      and STX1b), and syntaxin binding protein (MUNC-18) mRNAs were found to be
      increased in frontal cortex following comparison of AA with ANA animals.
      Bioinformatic analysis of these molecular targets showed that mGluR3 and cacna2d1
      fall within chromosomal locations reported to be alcohol-related by the
      Collaborative Study on the Genetics of Alcoholism (COGA) as well as quantitative
      trait loci (QTL) studies. To determine further whether these differences were
      strain specific, the above-mentioned genes were compared in ethanol-preferring
      (P) and -nonpreferring (NP) selected lines. VAMP2 was the only gene that
      displayed statistically different mRNA levels in a comparison of P and NP rats.
      In conclusion, the altered cortical gene expression illuminated here would have
      the effect of altering neurotransmitter release in AA rats (compared with ANA
      rats). Such alterations, however, might not be a universal characteristic of all
      animal models of alcohol abuse and will also require further investigation in
      post-mortem human samples.

PMID- 15846779
TI  - Rapid activation of JNK and p38 by glucocorticoids in primary cultured
      hippocampal cells.
AB  - Rapid activation of JNK and p38 and their translocation to the cell nucleus by
      glucocorticoids, corticosterone (Cort), and bovine serum-conjugated
      corticosterone (Cort-BSA) were studied in primary cultured hippocampal cells by
      using immunoblotting and immunofluorescence confocal microscopy. The rapid
      activation occurred 5 min after stimulation and was maintained at plateau for as
      long as 2-4 hr; i.e., the response persisted for 2 hr after washing out the 15
      min application of Cort-BSA. The activation occurred at a minimal concentration
      of 10(-9) M for Cort and 10(-8) M for Cort-BSA. GDPbetaS blocked the activation,
      but RU38486, a nuclear glucocorticoid receptor antagonist, could not block the
      activation, indicating the involvement of the membrane-delineated receptor in
      this reaction. The protein kinase C (PKC) inhibitor Go6976 blocked the response,
      whereas the protein kinase A inhibitor H89 could not, implying the involvement of
      PKC in the intracellular signal transduction pathway. The nongenomic nature of
      the responses and the transduction pathway and the significance of persistent
      action and biological significance are discussed.

PMID- 15846780
TI  - Involvement of Ca2+/calmodulin-dependent protein kinase II in the modulation of
      indolamines in diabetic and hyperglycemic rats.
AB  - Hyperglycemia and acidosis are the key factors in diabetic complications. It has
      been shown that acute or chronic diabetes alters serotonin levels in brain.
      However, the mechanism of hyperglycemia- or acidosis-induced changes in serotonin
      levels remains poorly understood. Because Ca2+-dependent protein kinases play a
      major role in the regulation of serotonin synthesis and release, we investigated
      the effect of diabetes, hyperglycemia, and acidosis on the level of indolamines
      [5-hydroxytryptamine (5-HT) and/or 5-hydroxyindoleacetic acid (5-HIAA)] and
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) enzyme activity or protein
      expression in different brain regions. Alloxan-induced (45 mg/kg bw) diabetic
      rats (30 days) showed increased level of 5-HT in striatum (ST; 183%), midbrain
      (MB; 199%), pons medulla (PM; 151%), cerebellum (CB; 214%), and cerebral cortex
      (CCX; 162%) compared with control (P < 0.05), and these changes were reversed
      after insulin administration. Rats treated with glucose (500 mg/kg bw) for 30
      days showed a 146%, 183%, 208%, and 177% (P < 0.05) increase in 5-HT levels in
      ST, PM, CB, and CCX, respectively. 5-HIAA level increased in hippocampus (HC;
      172%) and in MB (145%; P < 0.05). In addition, rats treated with sodium
      acetoacetate (NaAcAc) for 30 days (60 mg/kg bw) showed significant increases (P <
      0.05) of 5-HT level in ST (152%) and MB (174%). However, the levels of 5-HIAA
      increased only in MB (151%, P < 0.05). Rats treated with NH4Cl, which induced
      acidosis (150 mg/kg bw), showed an increased level of 5-HT only in HC (165%, P <
      0.05). The increased activity and protein expression of CaMKII in ST, MB, PM, CB,
      and CCX under diabetic conditions were correlated with the levels of indolamines
      changes during diabetic, hyperglycemic, or acidotic conditions. These results
      suggest that CaMKII may be involved in the regulation of indolamines in diabetic
      animals.

PMID- 15846781
TI  - Counteraction by repetitive daily exposure to static magnetism against sustained
      blockade of N-methyl-D-aspartate receptor channels in cultured rat hippocampal
      neurons.
AB  - In rat hippocampal neurons cultured with the antagonist for N-methyl-D-aspartate
      (NMDA) receptors dizocilpine (MK-801) for 8 days in vitro (DIV), a significant
      decrease was seen in the expression of microtubule-associated protein-2 (MAP-2)
      as well as mRNA for both brain-derived neurotrophic factor (BDNF) and growth
      associated protein-43 (GAP-43), in addition to decreased viability. MK-801 not
      only decreased the expression of the NR1 subunit of NMDA receptors but also
      increased NR2A expression, without affecting NR2B expression. Repetitive daily
      exposure to static magnetic fields at 100 mT for 15 min led to a decrease in the
      expression of MAP-2, without significantly affecting cell viability or the
      expression of neuronal nuclei (NeuN) and GAP-43. However, the repetitive
      magnetism prevented decreases in both BDNF mRNA and MAP-2 and additionally
      increased the expression of NR2A subunit, without altering NR1 expression in
      neurons cultured in the presence of MK-801. Repetitive magnetism was also
      effective in preventing the decrease by MK-801 in the ability of NMDA to increase
      intracellular free Ca2+ ions, without affecting the decrease in the maximal
      response. These results suggest that repetitive magnetism may at least in part
      counteract the neurotoxicity of MK-801 through modulation of the expression of
      particular NMDA receptor subunits in cultured rat hippocampal neurons.

PMID- 15846782
TI  - Spinal cord injury is accompanied by chronic progressive demyelination.
AB  - Preceding the development of therapeutic strategies for spinal cord injury is an
      identification of those pathological processes that might serve as therapeutic
      targets. Although demyelination has been documented as a secondary degenerative
      component of spinal cord injury in several species including humans, the extent
      of demyelination and its functional consequence remain unknown. In this report,
      we document the extent of demyelination and remyelination up to 450 days
      following contusive spinal cord injury in adult rats. The overall number of
      demyelinated axons peaked at 1 day post injury, declined by 7-14 days post
      injury, and then progressively increased up to 450 days post injury.
      Oligodendrocyte and Schwann cell remyelinated axons appeared by 14 days post
      injury. Although remyelinated axons were present from 14 to 450 days post injury,
      remyelination was incomplete, as indicated by the presence of demyelinated axons
      at every time point examined. These studies demonstrate for the first time that
      spinal cord injury is accompanied by chronic progressive demyelination, and they
      substantiate demyelination as a target for therapeutic intervention.

PMID- 15846783
TI  - Nerve growth factor-mediated collateral sprouting of central sensory axons into
      deafferentated regions of the dorsal horn is enhanced in the absence of the p75
      neurotrophin receptor.
AB  - This study examined the growth capacity of nerve growth factor (NGF)-responsive
      dorsal root ganglion (DRG) central processes using mice of the following
      genotypes: wildtype, p75 neurotrophin receptor (p75NTR) exon III null mutant, NGF
      transgenic, and NGF transgenic with p75NTR exon III null mutation (NGF/p75(-/-)).
      In wildtype and p75NTR exon III null mutant mice calcitonin gene-related peptide
      (CGRP) immunoreactivity in the dorsal horn is dramatically reduced at both 3 and
      28 days after rhizotomy. NGF transgenic and NGF/p75(-/-) mice also display
      reduced CGRP immunoreactivity 3 days after rhizotomy, but by postsurgical day 28
      significant increases in the density of CGRP-positive axons are observed in the
      injured dorsal horns of these mice. Interestingly, NGF/p75(-/-) mice displayed
      significantly more new axonal growth when compared to NGF transgenic mice
      expressing full-length p75NTR. Immunohistochemical and ultrastructural analyses
      revealed that this axonal growth is not the result of regeneration but rather
      injury-induced sprouting by intact DRG central processes into the lesion site.
      This collateral growth is restricted to deafferentated areas of the dorsal horn,
      and we therefore propose that this is an example of compensatory sprouting by NGF
      sensitive axons in the spinal cord, a response that is enhanced in the absence of
      NGF binding to p75NTR.

PMID- 15846784
TI  - Double bouquet cell in the human cerebral cortex and a comparison with other
      mammals.
AB  - Double bouquet cells (DBCs) are neocortical gamma-aminobutyric acid (GABA)ergic
      interneurons characterized by the vertical bundling of its axon, which are
      generally termed "bundles" or "horse-tails." Using immunocytochemistry for the
      calcium binding protein calbindin, we have analyzed the morphology, density, and
      distribution of DBC horse-tails in different cortical areas of the human cortex
      (Brodmann's areas 10, 4, 3b, 22, 18, and 17). Although DBC horse-tails were very
      numerous and regularly distributed in all cortical areas, variations were
      observed both in terms of morphology and density. We distinguished two major
      classes of DBC horse-tails: the thicker complex type (type I) that had more axon
      collaterals; and the simple type (type II). The density of DBC horse-tails was
      significantly higher in areas 17, 18, 22, and 4 than in areas 3b and 10.
      Moreover, the proportion of type I and type II DBC horse-tails varied in the
      cortical areas studied. We also examined the distribution of DBC horse-tails in
      frontal, parietal, and occipital areas of different mammalian species. We found
      DBCs to be present in carnivores but not in rodents, lagomorphs, or artiodactyls.
      In carnivores, relatively few DBC horse-tails can be identified and they were
      generally found in the occipital cortex. Therefore, there is significant
      variability in the morphology and distribution of DBC horse-tails in different
      species and cortical areas. We conclude that, although these interneurons may be
      an important element in the organization of cortical microcolumns in primates,
      this is not the case in other mammalian species.

PMID- 15846786
TI  - The organization of projections from the amygdala to visual cortical areas TE and
      V1 in the macaque monkey.
AB  - We examined the organization of amygdaloid projections to visual cortical areas
      TE and V1 by injecting anterograde tracers into the amygdaloid complex of Macaca
      fascicularis monkeys. The magnocellular and intermediate divisions of the basal
      nucleus of the amygdala gave rise to heavy projections to both superficial layers
      (border of I/II) and deep layers (V/VI) throughout the rostrocaudal extent of
      area TE. Although most of the injections led to heavier fiber and terminal
      labeling in the superficial layers of area TE, the most dorsal injections in the
      basal nucleus produced denser labeled fibers and terminals in the deep layers of
      area TE. Area V1 received projections primarily from the magnocellular division
      of the basal nucleus, and these terminated exclusively in the superficial layers.
      As in area TE, projections from the amygdala to area V1 were distributed
      throughout its rostrocaudal and transverse extents. Labeled axons demonstrated
      11.67 varicosities/100 microm on average in the superficial layers of area TE and
      8.74 varicosities/100 microm in the deep layers. In area V1 we observed 8.24
      varicosities/100 microm. Using confocal microscopy, we determined that at least
      55% of the tracer-labeled varicosities in areas TE and V1 colocalized
      synaptophysin, a marker of synaptic vesicles, indicating that they are probably
      synaptic boutons. Electron microscopic examination of a sample of these
      varicosities confirmed that labeled boutons formed synapses in areas TE and V1.
      These feedback-like projections from the amygdala have the potential of
      modulating key areas of the visual processing system.

PMID- 15846787
TI  - Long distance selective fiber outgrowth of transplanted hNT neurons in white
      matter tracts of the adult rat brain.
AB  - Terminally differentiated neurons derived from a human teratocarcinoma cell line
      (NT2N or hNT neurons) are promising as a cell source for transplantation, as they
      have been shown to be safe for transplantation in humans. We have shown
      previously that hNT neurons can express a catecholaminergic phenotype in a rat
      Parkinson model. In this study, we investigated the long-term survival and
      ability of hNT neurons to express tyrosine hydroxylase and reconstruct the
      dopamine-denervated nigrostriatal pathway. Hemiparkinsonian rats received grafts
      of 400,000 viable hNT neurons into each of the denervated striatum and substantia
      nigra. Robust hNT grafts were detected up to 24 weeks posttransplantation,
      although few cells expressed tyrosine hydroxylase. Many hNT fibers were often
      associated with ipsilateral and contralateral white matter tracts--corpus
      callosum, rostral migratory stream, optic tract, and external capsule. Fewer
      fibers were associated with the superior cerebellar peduncle, medial lemniscus,
      and nigrostriatal pathway. Axons also projected into the frontal cortex and
      extended parallel to the surface of the brain in the superficial cortical layers.
      These pathways were seen in all grafted animals, suggesting that specific
      guidance cues exist in the adult brain governing hNT fiber outgrowth. Injured
      adult axons and transplanted embryonic neuronal axons rarely extend for such
      distances in the adult nervous system. We propose that elucidating the factors
      promoting and guiding hNT axonal outgrowth could provide important clues to
      enhancing regeneration and target reinnervation in the adult brain, two factors
      of critical importance for cell restoration strategies aimed at brain repair.

PMID- 15846788
TI  - Topography of pig retinal ganglion cells.
AB  - In the present work we analyzed the distribution of retinal ganglion cells (RGCs)
      in the pig retina. RGCs were retrogradely labeled in vivo by injecting Fluoro
      Gold into the optic nerve. RGC density and the distribution of RGCs in terms of
      soma size were analyzed. Different regions of the porcine retina were identified
      following analysis of the distribution of RGCs in terms of cell density and soma
      size: in the central retina, we found a high-density horizontal RGC band lying
      dorsal to the optic disc. Moreover, in this region, a high proportion of RCGs
      with small soma size was observed. From the central to the more peripheral
      retina, we observed a decrease in RGC density, together with a greater presence
      of RGCs with larger somas. The results of this study should prove to be useful as
      a foundation for future studies with the porcine retina as a model in ophthalmic
      research. The study also highlights the necessity to label the RGC population
      specifically with retrograde tracers in order to quantify precisely alterations
      in the cell population associated with experimental treatments.

PMID- 15846789
TI  - Prevalence of five previously reported and recurrent BRCA1 genetic rearrangement
      mutations in 20,000 patients from hereditary breast/ovarian cancer families.
AB  - Many rearrangement mutations in the BRCA1 gene have been identified. It is
      becoming clear that some of these mutations are prevalent, and therefore their
      detection is necessary in order for clinical genetic tests to have high
      sensitivity. Published information on particular rearrangements is frequently
      limited to a single patient, small groups of patients, or patients of a
      particular ethnicity. The objectives of this work included characterizing the
      prevalence of five specific rearrangement mutations in a large North American
      patient population. A mutation-specific multiplex PCR assay was used for
      determining the prevalence of five BRCA1 rearrangement mutations that previously
      had been reported to occur in unrelated patients. The mutation status of these
      rearrangements, which came from 20,712 patients at high risk for hereditary
      breast and/or ovarian cancers who had submitted specimens for clinical genetic
      testing, is presented. The results, obtained from 2,634 mutation carriers, showed
      a 6-kb duplication of exon 13, identified in 53 patients (2.01%); a 26-kb
      deletion encompassing exons 14-20, detected in seven patients (0.27%); a 510-bp
      deletion of exon 22, detected in 5 patients (0.19%); and a 3.4-kb deletion of
      exon 13, detected in one patient (0.04%). A previously reported 7.1-kb deletion
      of exons 8-9 was not found. The high frequency of the exon 13 duplication makes
      it the fourth most prevalent mutation in these patients. These results provide an
      accurate picture of the prevalence of these mutations in hereditary
      breast/ovarian cancer patients undergoing genetic testing in North America.

PMID- 15846790
TI  - Acute myeloid leukemia with a complex aberrant karyotype is a distinct biological
      entity characterized by genomic imbalances and a specific gene expression
      profile.
AB  - Acute myeloid leukemia (AML) with a complex aberrant karyotype is a distinct
      biological entity. It is characterized by: (1) a sharp increase in incidence
      above age 50; (2) a characteristic pattern of chromosomal gain and, especially,
      loss, that is, of 5q14q33, 7q32q35, and 17p13, translating into reduced
      expression of genes in these regions; (3) a unique gene expression pattern
      including up-regulation of genes involved in DNA repair; (4) a high incidence of
      TP53 deletions and/or mutations; and (5) an overall unfavorable prognosis.
      Further unraveling the biology of AML with a complex aberrant karyotype by gene
      expression profiling may provide deeper insights into the pathogenesis of as well
      as the reasons for chemoresistance in this AML subtype. These data may be the
      basis for developing targeted therapeutic strategies to increase the cure rate in
      patients with AML and a complex aberrant karyotype.

PMID- 15846791
TI  - Targeted expression of anti-apoptotic protein p35 in oligodendrocytes reduces
      delayed demyelination and functional impairment after spinal cord injury.
AB  - Functional impairment after spinal cord injury (SCI) is attributed to neuronal
      cell necrosis death and axonotmesis, with further worsening caused by the
      accompanying apoptosis of myelin-forming oligodendrocytes (OLGs). However, it is
      unclear as to how much OLG apoptosis contributes to functional impairment. To
      address this issue, we used transgenic mice characterized by the targeted
      expression of p35, a broad-spectrum caspase inhibitor, in OLGs using the cre/loxP
      system (referred to as cre/p35 transgenic mice). In this study, we examined the
      motor function and histopathologic changes after a contusive thoracic spinal cord
      injury in the cre/p35 transgenic mice. A larger number of OLGs and a lesser
      extent of demyelination were observed after SCI in the cre/p35 transgenic mice
      than in the control cre mice, which did not carry the p35 transgene. Furthermore,
      the motor function of the hindlimbs recovered to a significantly better degree in
      the cre/p35 transgenic mice than in the control cre mice. Thus, the inhibition of
      OLG apoptosis decreased the extent of functional impairment after SCI. These
      findings suggest that the inhibition of OLG apoptosis may be a potential
      treatment for SCI.

PMID- 15846792
TI  - Microglia as potential contributors to motor neuron injury in amyotrophic lateral
      sclerosis.
AB  - The central nervous system (CNS) is equipped with a variety of cell types, all of
      which are assigned particular roles during the development, maintenance, function
      and repair of neural tissue. One glial cell type, microglia, deserves particular
      attention, as its role in the healthy or injured CNS is incompletely understood.
      Evidence exists for both regenerative and degenerative functions of these glial
      cells during neuronal injury. This review integrates the current knowledge of the
      role of microglia in an adult-onset neurodegenerative disease, amyotrophic
      lateral sclerosis (ALS), and pays particular attention to the possible mechanisms
      of initiation and propagation of neuronal damage during disease onset and
      progression. Microglial cell properties, behavior and detected inflammatory
      reactions during the course of the disease are described. The neuroinflammatory
      changes that occur in a mouse model of ALS are summarized. The understanding of
      microglial function in the healthy and injured CNS could offer better diagnostic
      as well as therapeutic approaches for prevention, retardation, or repair of
      neural tissue degeneration.

PMID- 15846793
TI  - Delayed repair of corticospinal tract lesions as an assay for the effectiveness
      of transplantation of Schwann cells.
AB  - We have previously shown that cultured adult olfactory ensheathing cells injected
      after 8 weeks into functionally complete unilateral lesions of the rat
      corticospinal tract induce restoration of paw reaching function to about 50% of
      normal, starting at around 10 days after transplantation. This provides an assay
      for determining the effectiveness of different methods of cell preparation or
      different cell types. We report that transplantation of cultured adult peripheral
      nerve Schwann cells also restores function, but the effect is delayed until
      around 30 days after transplantation and reaches only around 5-10% of normal. The
      presence of fibroblasts in the Schwann cell cultures neither improves, nor
      impairs the reparative effect, but fibroblasts alone (without Schwann cells) have
      no reparative effect. Without transplantation of exogenous Schwann cells, the
      ingrowth of endogenous Schwann cells which occurs spontaneously into these
      lesions does not restore function.

PMID- 15846795
TI  - Potassium homeostasis in the ischemic brain.
AB  - Extracellular [K+] can range within 2.5-3.5 mM under normal conditions to 50-80
      mM under ischemic and spreading depression events. Sustained exposure to elevated
      [K+]o has been shown to cause significant neuronal death even under conditions of
      abundant glucose supply. Astrocytes are well equipped to buffer this initial
      insult of elevated [K] through extensive gap junctional coupling, Na+/K+ pump
      activity (with associated glycogen and glycolytic potential), and endfoot
      siphoning capability. Their abundant energy availability and alkalinizing
      mechanisms help sustain Na+/K+ ATPase activity under ischemic conditions.
      Furthermore, passive K+ uptake mechanisms and water flux mediated through
      aquaporin-4 channels in endfoot processes are important energy-independent
      mechanisms. Unfortunately, as the length of ischemic episode is prolonged, these
      mechanisms increase to a point where they begin to have repercussions on other
      important cellular functions. Alkalinizing mechanisms induce an elevation of
      [Na+]i, increasing the energy demand of Na+/K+ ATPase and leading to eventual
      detrimental reversal of the Na+/glutamate- cotransporter and excitotoxic damage.
      Prolonged ischemia also results in cell swelling and activates volume regulatory
      processes that release excessive excitatory amino acids, further exacerbating
      excitotoxic injury. In the days following ischemic injury, reactive astrocytes
      demonstrate increased cell size and process thickness, leading to improved
      spatial buffering capacity in regions outside the lesion core where there is
      better neuronal survival. There is a substantial heterogeneity among reactive
      astrocytes, with some close to the lesion showing decreased buffering capacity.
      However, it appears that both Na+/K+ ATPase activity (along with energy
      production processes) as well as passive K+ uptake mechanisms are upregulated in
      gliotic tissue outside the lesion to enhance the above-mentioned homeostatic
      mechanisms.

PMID- 15846794
TI  - CD163-positive perivascular macrophages in the human CNS express molecules for
      antigen recognition and presentation.
AB  - Perivascular macrophages (PVM) constitute a subpopulation of resident macrophages
      in the central nervous system (CNS) that by virtue of their strategic location at
      the blood-brain barrier potentially lend themselves to a variety of important
      functions in both health and disease. Functional evidence suggests that PVM play
      a supportive role during experimental autoimmune encephalomyelitis in rodents.
      However, the function of PVM in the human CNS remains poorly characterized. We
      first set out to investigate the validity of the antibody EDhu1, which recognizes
      human CD163, to specifically identify human PVM. Second, we wanted to gain
      insight into the function of PVM in antigen recognition and presentation and
      therefore we studied the expression of DC-SIGN, mannose receptor, MHC class II,
      and several costimulatory molecules by PVM in the normal and inflamed human CNS
      (multiple sclerosis (MS) brain lesions). Conventional immunohistochemistry and
      double-labeled immunofluorescence techniques were used. We show that CD163
      specifically reveals PVM in the normal human CNS. In MS lesions, CD163 staining
      reveals expression on foamy macrophages and microglia, besides an upregulation of
      the amount of PVM stained. In contrast, mannose receptor expression is restricted
      to PVM in both normal and inflamed brain tissue. Furthermore, we show that a
      subpopulation of PVM in the human brain express several molecules involved in
      antigen recognition, presentation, and costimulation. Therefore PVM, which occupy
      a strategic location at the BBB, are equipped to recognize antigen and present it
      to T cells, supporting a role in the regulation of perivascular inflammation in
      the human CNS.

PMID- 15846796
TI  - Glial nitric oxide and ischemia.
AB  - One of the responses to cerebral ischemia is an increase in the production of
      nitric oxide, catalyzed by enzymes expressed in both resident and infiltrating
      cells. The nitric oxide that is generated does contribute to the ensuing
      pathology, but it can also be beneficial. The effects of nitric oxide depend on
      the cell site of production, the amount generated, and the chemical nature of the
      products of further oxidation. Understanding how nitric oxide production from
      microglia and astrocytes contributes to ischemic pathology is important for the
      development and application of future therapeutics based on inhibiting or
      amplifying its production in the injured brain.

PMID- 15846797
TI  - Astrocytic swelling in cerebral ischemia as a possible cause of injury and target
      for therapy.
AB  - In this viewpoint article, I summarize data showing that the astrocytic swelling
      that occurs early after the acute CNS pathologies ischemia and traumatic brain
      injury is damaging. We have proposed that one reason may be the release of
      excitatory amino acids (EAA) via volume-activated anion channels (VRACs) that are
      activated by such swelling. This release could be a target for therapy, which
      could involve blocking the astrocytic swelling or the release mechanisms. The
      transport mechanisms likely causing the early astrocytic swelling are therefore
      summarized. In terms of targeting the release mechanisms, we have found a potent
      inhibitor of VRACs, tamoxifen, to be strongly neuroprotective in focal ischemia
      with a therapeutic window of 3 h after initiation of the ischemia. The question,
      however, of whether neuroprotection by tamoxifen can be solely attributed to VRAC
      inhibition in astrocytes has yet to be resolved.

PMID- 15846798
TI  - Failure and function of intracellular pH regulation in acute hypoxic-ischemic
      injury of astrocytes.
AB  - Astrocytes can die rapidly following ischemic and traumatic injury to the CNS.
      Brain acid-base status has featured prominently in theories of acute astrocyte
      injury. Failure of astrocyte pH regulation can lead to cell loss under conditions
      of severe acidosis. By contrast, the function of astrocyte pH regulatory
      mechanisms appears to be necessary for acute cell death following the simulation
      of transient ischemia and reperfusion. Severe lactic acidosis, and the failure of
      astrocytes to regulate intracellular pH (pH(i)) have been emphasized in brain
      ischemia under hyperglycemic conditions. Direct measurements of astrocyte pH(i)
      after cardiac arrest demonstrated a mean pH(i) of 5.3 in hyperglycemic rats. In
      addition, both in vivo and in vitro studies of astrocytes have shown similar pH
      levels to be cytotoxic. Whereas astrocytes exposed to hypoxia alone may require
      12-24 h to die, acidosis has been found to exacerbate and speed hypoxic loss of
      these cells. Recently, astrocyte cultures were exposed to hypoxic, acidic media
      in which the large ionic perturbations characteristic of brain ischemia were
      simulated. Upon return to normal saline ("reperfusion"), the majority of cells
      died. This injury was dependent on external Ca2+ and was prevented by inhibition
      of reversed Na(+)-Ca2+ exchange, blockade of Na(+)-H+ exchange, or by low pH of
      the reperfusion saline. These data suggested that cytotoxic elevation of [Ca2+]i
      occurred during reperfusion due to a sequence of activated Na(+)-H+ exchange,
      cytosolic Na+ loading, and resultant reversal of Na(+)-Ca2+ exchange. The
      significance of this reperfusion model to ischemic astrocyte injury in vivo is
      discussed.

PMID- 15846799
TI  - Fibrin-modifying serine proteases thrombin, tPA, and plasmin in ischemic stroke:
      a review.
AB  - Ischemic stroke is a sudden loss of circulation to a portion of the brain that
      results in a loss of neurologic function. Many ischemic strokes are embolic. They
      result from a thrombus traveling into the central circulation and occluding a
      blood vessel. Treatment of ischemic stroke with recombinant tissue plasminogen
      activator (tPA) can improve patient outcomes. However, tPA must be used during a
      specific time window after the stroke onset to be effective and it risks
      converting an ischemic stroke into a hemorrhagic one. We explore the basic
      effects of fibrin-modifying proteases on neurons, astrocytes, and microglia
      during ischemia. tPA, thrombin, and plasmin can initiate microglial activation
      and change both neuronal and astrocytic survival. As a result of these functions
      and of their role in blood homeostasis, all three of these proteases have
      profound effects on neurons and glial cells in the brain and are capable of
      altering the development and severity of ischemic stroke.

PMID- 15846800
TI  - Alterations in metabolism and gap junction expression may determine the role of
      astrocytes as "good samaritans" or executioners.
AB  - Our knowledge of astroglia and their physiological and pathophysiological role(s)
      in the central nervous system (CNS) has grown during the past decade, revealing a
      complex picture. It is becoming increasingly clear that glia play a significant
      role in the homeostasis and function of the CNS and that neurons should no longer
      be considered the only cell type that responds, both rapidly and slowly, to
      electrochemical activity. We discuss recent advances in the field with an
      emphasis on the impact of hypoxia and ischemia on astrocytic metabolism and the
      functional relationship between glucose metabolism and gap junctions in
      astrocytes. We also address the controversy over whether astrocytic gap junctions
      mediate protection or killing of neurons during or after hypoxic or ischemic
      insults.

PMID- 15846801
TI  - Identification of oligodendrocytes in experimental disease models.
AB  - The ability to identify oligodendrocytes in culture, in fixed tissue, and in vivo
      using unique markers is a requisite step to understanding their responses in any
      damage, recovery, or developmental process. Their nuclei are readily seen in
      histological preparations of healthy white and gray matter, and their cell bodies
      can be reliably identified with a variety of immunocytochemical markers. However,
      there is little consensus regarding optimal methods to assess oligodendrocyte
      survival or morphology under experimental injury conditions. We review common
      approaches for histological and immunocytochemical identification of these cells.
      Transgenic and viral methods for cell type-selective transfer of genes encoding
      fluorescent proteins offer promising new approaches for manipulating and
      visualizing oligodendrocytes in models of health and disease.

PMID- 15846802
TI  - Multiple roles for MMPs and TIMPs in cerebral ischemia.
AB  - Matrix metalloproteinases (MMPs) are matrix-degrading enzymes involved in diverse
      homeostatic and pathological processes. Several MMPs are expressed within the CNS
      and serve important normal and pathological functions during development and
      adulthood. An early and major pathological effect of MMP activity after cerebral
      ischemia is opening of the blood-brain barrier (BBB). More recent work
      demonstrates emerging roles for MMPs and their natural inhibitors, tissue
      inhibitors of metalloproteinases (TIMPs), in the regulation of neuronal cell
      death. In addition, MMPs and TIMPs are likely to play important roles during the
      repair phases of cerebral ischemia, particularly during angiogenesis and
      reestablishment of cerebral blood flow. This review attempts to elucidate how
      MMPs and TIMPs may provide detrimental or beneficial actions during the injury
      and repair processes after cerebral ischemia. These processes will have important
      implications for therapies using MMP inhibitors in stroke.

PMID- 15846803
TI  - Ischemia-induced programmed cell death in astrocytes.
AB  - Astrocytes are essential for neuronal survival and function, neurogenesis, and
      neural repair. Although astrocytes are more resistant than neurons to most stress
      conditions in vitro, certain astrocyte subtypes, such as the glial fibrillary
      acidic protein (GFAP)-negative protoplasmic astrocytes that predominate in gray
      matter structures, may be equally or more sensitive than neurons to ischemia in
      vivo. Programmed cell death differs from passive, necrotic death in that cell
      constituents actively participate in cell demise. Like neurons, astrocytes
      undergo programmed cell death during normal development. Cell culture studies
      have shown that astrocytes can be induced to undergo apoptosis and other forms of
      programmed cell death by many factors relevant to ischemia, including acidosis,
      oxidative stress, substrate deprivation, and cytokines. Animal models of cerebral
      ischemia have confirmed nuclear condensation and upregulation of Bax and caspases
      in a subset of astrocytes exposed to ischemia, especially in immature brain. A
      causal role for these events in astrocyte death is supported by improved
      astrocyte survival after inhibition of caspase-dependent cell death pathways.
      Astrocyte survival is also improved by blocking the poly(ADP-ribose)-1 cell death
      pathway. Markers of programmed cell death are generally less evident and less
      widespread in astrocytes than in neighboring neurons. However, most studies to
      date have relied only on markers of classical apoptosis. In addition, these
      studies have relied almost exclusively on GFAP to identify astrocytes. Since most
      protoplasmic astrocytes are poorly immunoreactive for GFAP, the extent of
      ischemia-induced programmed cell death in this cell type remains uncertain.

PMID- 15846804
TI  - Neuroprotective role of astrocytes in cerebral ischemia: focus on ischemic
      preconditioning.
AB  - Following focal cerebral ischemia ("stroke") a complex and dynamic interaction of
      vascular cells, glial cells, and neurons determines the extent of the ensuing
      lesion. Traditionally, the focus has been on mechanisms of damage, while recently
      it has become clear that endogenous mechanisms of protection are equally
      important for the final outcome. Glial cells, in particular astrocytes, have
      always been viewed as supporters of neuronal function. Only recently a very
      active role for glial cells has been emerging in physiology and pathophysiology.
      Not surprisingly, then, specific protective pathways have been identified by
      which these cells can protect or even help to regenerate brain tissue after acute
      insults. However, as exemplified by the existence of the glial scar, which forms
      around lesioned brain tissue, is composed mainly of astrocytes and plays a key
      role in regeneration failure, it is an oversimplification to assign merely
      protective functions to astrocytes. The present review will discuss the role of
      astrocytes in ischemic brain injury with a focus on neuroprotection in general.
      In this context we will consider particularly the phenomenon of "ischemic
      tolerance," which is an experimental paradigm helpful in discriminating
      destructive from protective mechanisms after cerebral ischemia.

PMID- 15846805
TI  - Astrocyte activation and reactive gliosis.
AB  - Astrocytes become activated (reactive) in response to many CNS pathologies, such
      as stroke, trauma, growth of a tumor, or neurodegenerative disease. The process
      of astrocyte activation remains rather enigmatic and results in so-called
      "reactive gliosis," a reaction with specific structural and functional
      characteristics. In stroke or in CNS trauma, the lesion itself, the ischemic
      environment, disrupted blood-brain barrier, the inflammatory response, as well as
      in metabolic, excitotoxic, and in some cases oxidative crises--all affect the
      extent and quality of reactive gliosis. The fact that astrocytes function as a
      syncytium of interconnected cells both in health and in disease, rather than as
      individual cells, adds yet another dimension to this picture. This review focuses
      on several aspects of astrocyte activation and reactive gliosis and discusses its
      possible roles in the CNS trauma and ischemia. Particular emphasis is placed on
      the lessons learnt from mouse genetic models in which the absence of intermediate
      filament proteins in astrocytes leads to attenuation of reactive gliosis with
      distinct pathophysiological and clinical consequences.

PMID- 15846806
TI  - Astrocytes in cerebral ischemic injury: morphological and general considerations.
AB  - Asrocytic responses constitute one of the earliest and most prominent changes in
      the CNS following ischemic injury. Astrocytes are known to carry out critical
      functions such as maintenance of ionic homeostasis, prevention of excitotoxicity,
      scavenging free radicals, provision of nutrients and growth factors, promotion of
      neovascularization, and support of synaptogenesis and neurogenesis that
      potentially may influence the outcome of ischemic injury. This article reviews
      ischemia-associated alterations in astrocytes and their potential significance.
      Interactions with neurons, microglia, and endothelial cells are also considered.
      This article highlights the critical role of astrocytes in the CNS response to
      ischemic injury.

PMID- 15846807
TI  - Role of glial cells in cerebral ischemia.
AB  - Despite intense efforts at the bench and at the bedside, few therapeutic
      strategies exist to combat the consequences of cerebral ischemia. Traditionally,
      a "neurocentric" view has dominated research in this field. Evidence is now
      accumulating that glial cells, in particular astrocytes, play an active and
      important role in the pathophysiology of cerebral ischemia. Brain energetics,
      water and ion homeostasis, inflammation, trophic factor production, vascular
      regulation, neuroneogenesis, and vasculogenesis, among others, are all under the
      control of glial cells. As a consequence, glial cells have been identified as
      promising targets for novel therapeutic approaches in brain protection. This
      review aims at dissecting possible protective as well as destructive roles of
      astrocytes (and other glial cells) in cerebral ischemia. By emphasizing open
      issues in this field, we hope to stimulate further research into this relatively
      unexplored aspect of brain pathophysiology.

PMID- 15846808
TI  - Astrocytic contributions to bioenergetics of cerebral ischemia.
AB  - Astrocytes are multifunctional cells that interact with neurons and other
      astrocytes in signaling and metabolic functions, and their resistance to
      pathophysiological conditions can help restrict loss of tissue after an ischemic
      event provided adequate nutrients are supplied to support their requirements.
      Astrocytes have substantial oxidative capacity and mechanisms to upregulate
      glycolytic capability when respiration is impaired. An astrocytic enzyme that
      synthesizes a powerful activator of glycolysis is not present in neurons,
      endowing astrocytes with the ability to sustain ATP production under restrictive
      conditions. The monocarboxylic acid transporter (MCT) isoforms predominating in
      astrocytes are optimized to facilitate very large increases in lactate flux as
      lactate concentration increases within (1-3 mM) and above (>3 mM) the normal
      range. In sharp contrast, the major neuronal MCT serves as a barrier to increased
      transmembrane transport as lactate rises above 1 mM, restricting both entry and
      efflux. Lactate can serve as fuel during recovery from ischemia but direct
      evidence that lactate is oxidized by neurons (vs. astrocytes) to maintain
      synaptic function is lacking. Astrocytes have critical roles in regulation of
      ionic homeostasis and control of extracellular glutamate levels, and spreading
      depression associated with ischemia places high demands on energy supplies in
      astrocytes and contributes to metabolic exhaustion and demise. Disruption of Ca2+
      homeostasis, generation of oxygen free radicals and nitric oxide, and
      mitochondrial depolarization contribute to astrocyte death during and after a
      metabolic insult. Novel pharmaceutical agents targeted to astrocytes and
      hyperoxic therapy that restores penumbral oxygen level during energy failure
      might improve postischemic outcome.

PMID- 15846809
TI  - Automated analysis of meta-analysis networks.
AB  - The high information content in large data sets from voxel-based meta-analyses is
      complex, making it hard to readily resolve details. Using the meta-analysis
      network as a standardized data structure, network analysis algorithms can examine
      complex interrelationships and resolve hidden details. Two new network analysis
      algorithms have been adapted for use with meta-analysis networks. The first,
      called replicator dynamics network analysis (RDNA), analyzes co-occurrence of
      activations, whereas the second, called fractional similarity network analysis
      (FSNA), uses binary pattern matching to form similarity subnets. These two
      network analysis methods were evaluated using data from activation likelihood
      estimation (ALE)-based meta-analysis of the Stroop paradigm. Two versions of
      these data were evaluated, one using a more strict ALE threshold (P < 0.01) with
      a 13-node meta-analysis network, and the other a more lax threshold (P < 0.05)
      with a 22-node network. Java-based applications were developed for both RDNA and
      FSNA. The RDNA algorithm was modified to provide multiple subnets or maximal
      cliques for meta-analysis networks. Three different similarity measures were
      evaluated with FSNA to form subsets of nodes and experiments. RDNA provides a
      means to gauge importance of metanalysis subnets and complements FSNA, which
      provides a more comprehensive assessment of node similarity subsets, experiment
      similarity subsets, and overall node-to-factors similarity. The need to use both
      presence and absence of activations was an important finding in similarity
      analyses. FSNA revealed details from the pooled Stroop meta-analysis that would
      otherwise require separate highly filtered meta-analyses. These new analysis
      tools demonstrate how network analysis strategies can simplify greatly and
      enhance voxel-based meta-analyses.

PMID- 15846810
TI  - BrainMap taxonomy of experimental design: description and evaluation.
AB  - Coordinate-based, voxel-wise meta-analysis is an exciting recent addition to the
      human functional brain mapping literature. In view of the critical importance of
      selection criteria for any valid meta-analysis, a taxonomy of experimental design
      should be an important tool for aiding in the design of rigorous meta-analyses.
      The coding scheme of experimental designs developed for and implemented within
      the BrainMap database provides a candidate taxonomy. In this study, the BrainMap
      experimental-design taxonomy is described and evaluated by comparing taxonomy
      fields to data-filtering choices made by subject-matter experts carrying out meta
      analyses of the functional imaging literature. Fifteen publications reporting a
      total of 46 voxel-wise meta-analyses were included in this assessment.
      Collectively these 46 meta-analyses pooled data from 351 publications, selected
      for experimental similarity within each meta-analysis. Filter implementations
      within BrainMap were graded by ease-of-use (A-C) and by stage-of-use (1-3).
      Quality filters and content filters were tabulated separately. Quality filters
      required for data entry into BrainMap were classed as mandatory (five filters),
      being above the use grading system. All authors spontaneously adopted the five
      mandatory filters in constructing their meta-analysis, indicating excellent
      agreement on data quality among authors and between authors and the BrainMap
      development team. Two non-mandatory quality filters (group size and imaging
      modality) were applied by all authors; both were Stage 1, Grade A filters. Field
      of-view filters were the least-accessible quality filters (Stage 3, Grade C); two
      field-of-view filters were applied by six and four authors, respectively. Authors
      made a total of 115 content-filter choices. Of these, 78 (68%) were Stage 1,
      Grade A filters; 16 (14%) were Stage 2, Grade A; and 21 (18%) were Stage 2, Grade
      C. No author-applied filter was absent from the taxonomy.

PMID- 15846811
TI  - ALE meta-analysis: controlling the false discovery rate and performing
      statistical contrasts.
AB  - Activation likelihood estimation (ALE) has greatly advanced voxel-based meta
      analysis research in the field of functional neuroimaging. We present two
      improvements to the ALE method. First, we evaluate the feasibility of two
      techniques for correcting for multiple comparisons: the single threshold test and
      a procedure that controls the false discovery rate (FDR). To test these
      techniques, foci from four different topics within the literature were analyzed:
      overt speech in stuttering subjects, the color-word Stroop task, picture-naming
      tasks, and painful stimulation. In addition, the performance of each thresholding
      method was tested on randomly generated foci. We found that the FDR method more
      effectively controls the rate of false positives in meta-analyses of small or
      large numbers of foci. Second, we propose a technique for making statistical
      comparisons of ALE meta-analyses and investigate its efficacy on different groups
      of foci divided by task or response type and random groups of similarly obtained
      foci. We then give an example of how comparisons of this sort may lead to
      advanced designs in future meta-analytic research.

PMID- 15846812
TI  - Meta-analysis of functional imaging data using replicator dynamics.
AB  - Despite the rapidly growing number of meta-analyses in functional neuroimaging,
      the field lacks formal mathematical tools for the quantitative and qualitative
      evaluation of meta-analytic data. We propose to use replicator dynamics in the
      meta-analysis of functional imaging data to address an important aspect of
      neuroimaging research, the search for functional networks of cortical areas that
      underlie a specific cognitive task. The replicator process requires as input only
      a list of activation locations, and it results in a network of locations that
      jointly show significant activation in most studies included in the meta
      analysis. These locations are likely to play a critical role in solving the
      investigated cognitive task. Our method was applied to a meta-analysis of the
      Stroop interference task using data provided by the publicly accessible database
      BrainMap DBJ.

PMID- 15846813
TI  - Brain activity associated with painfully hot stimuli applied to the upper limb: a
      meta-analysis.
AB  - The capacity of pain to alert against potential injury or focus attention on
      damaged tissue is enhanced by the intrinsically aversive nature of the
      experience. Finding methods to relieve pain will ultimately be facilitated by
      deeper understanding of the processes that contribute to the experience, and
      functional brain imaging has contributed substantially toward that end. An
      impressive body of literature has identified a distributed network of pain
      related activity in the brain that is subject to considerable modulation by
      different stimulus parameters, contextual factors, and clinical conditions. The
      fundamental substrates of the pain network are yet to be distilled from the
      highly variable results of studies published thus far. Qualitative reviews of the
      pain-imaging literature have been contributory, but lack the greater surety of
      quantitative methods. We employ the activation likelihood estimation (ALE) meta
      analytic technique to establish the most consistent activations among studies
      reporting brain responses subsequent to the application of noxious heat. A
      network of pain-related activity was replicated for stimuli to either upper limb
      that included two discernible regions of the mid-anterior cingulate cortex,
      bilateral thalami, insula, and opercula cortices, posterior parietal cortex,
      premotor cortex, supplementary motor area, and cerebellum. The findings of the
      meta-analysis resonate with other streams of information that continue to enhance
      our understanding of pain in the brain. The results also point toward new areas
      of research that may be fruitful for the exploration of central pain processing.

PMID- 15846814
TI  - Cortical regions involved in eye movements, shifts of attention, and gaze
      perception.
AB  - Human vision is an active process that involves shifting attention across the
      visual scene, with or without moving the eyes. Such shifts of attention can be
      generated at will (endogenously) or be triggered automatically, i.e., generated
      in response to exogenous stimuli including socially relevant cues such as someone
      else's gaze. What are the common and distinct brain mechanisms involved in these
      processes? To address this question, we carried out a quantitative effect
      location meta-analysis of 59 brain-imaging experiments whose results were
      published using standardized coordinates. For each condition of interest, namely
      voluntary and visually triggered eye movements, voluntary and visually triggered
      (covert) shifts of attention, and perception of someone else's gaze, we computed
      activation likelihood estimation (ALE) maps. Those maps represent at each voxel
      of the brain the probability of reporting a signal change related to the
      condition of interest. For eye movements, this analysis confirmed the spatial
      location of the frontal eye fields, supplementary eye fields, and parietal
      saccade-related regions. The map of covert shifts of attention demonstrated
      highest similarity with the map of saccadic eye movements. Gaze perception showed
      common activation likelihood with the other conditions in the right intraparietal
      sulcus and in the lateral precentral gyrus. It demonstrated more similarity with
      the reflexive than with the voluntary saccades and shifts of attention. We
      propose that a core network of frontoparietal and temporal brain regions is
      recruited when we shift the focus of our attention with or without eye movements
      in response to the appearance of a visual target, as well as when we see someone
      else shift his or her gaze.

PMID- 15846815
TI  - Stuttered and fluent speech production: an ALE meta-analysis of functional
      neuroimaging studies.
AB  - This study reports an activation likelihood estimation (ALE) meta-analysis of
      imaging studies of chronic developmental stuttering in adults. Two parallel meta
      analyses were carried out: (1) stuttered production in the stutterers; (2) fluent
      production in the control subjects. The control subjects' data replicated
      previous analyses of single-word reading, identifying activation in primary motor
      cortex, premotor cortex, supplementary motor area, Rolandic operculum, lateral
      cerebellum, and auditory areas, among others. The stuttering subjects' analysis
      showed that similar brain areas are involved in stuttered speech as in fluent
      speech, but with some important differences. Motor areas were over-activated in
      stuttering, including primary motor cortex, supplementary motor area, cingulate
      motor area, and cerebellar vermis. Frontal operculum, Rolandic operculum, and
      anterior insula showed anomalous right-laterality in stutterers. Auditory
      activations, due to hearing one's own speech, were essentially undetectable in
      stutterers. The phenomenon of efference copy is proposed as a unifying account of
      the pattern activation revealed within this ALE meta-analysis. This provides the
      basis for a stuttering system model that is testable and should help to advance
      the understanding and treatment of this disorder.

PMID- 15846816
TI  - Cerebellum and auditory function: an ALE meta-analysis of functional neuroimaging
      studies.
AB  - Over the past two decades neuroimaging data have accumulated showing that the
      cerebellum, traditionally viewed only as a motor structure, is also active in a
      wide variety of sensory and cognitive tasks. We have proposed that instead of
      explicit involvement in any particular motor, sensory, or cognitive task, the
      cerebellum performs a much more fundamental computation involving the active
      acquisition of sensory data. We carried out an activation likelihood estimate
      (ALE) meta-analysis to determine whether neuroimaging results obtained during a
      wide range of auditory tasks support this proposal. Specifically, we analyzed the
      coordinates of 231 activation foci obtained in 15 different auditory studies
      selected through an extensive search of the positron emission tomography (PET)
      and functional magnetic resonance imaging (fMRI) literature. The studies selected
      represent a wide variety of purely auditory tasks using highly controlled
      synthesized acoustic stimuli. The results clearly revealed that in addition to
      temporal auditory areas of cerebral cortex, specific regions in the cerebellum
      are activated consistently across studies regardless of the particular auditory
      task involved. In particular, one area in left lateral crus I area showed the
      greatest volume and ALE peak value among the extratemporal regions. A subanalysis
      was carried out that ruled out the specific association of this cerebellar
      cluster with attentional demand. The results are consistent with the hypothesis
      that the cerebellum may play a role in purely sensory auditory processing, and
      are discussed in light of the broader idea of the cerebellum subserving a
      fundamental sensory function.

PMID- 15846817
TI  - Neuroanatomical correlates of phonological processing of Chinese characters and
      alphabetic words: a meta-analysis.
AB  - We used the activation likelihood estimation (ALE) method to quantitatively
      synthesize data from 19 published brain mapping studies of phonological
      processing in reading, six with Chinese and 13 with alphabetic languages. It
      demonstrated high concordance of cortical activity across multiple studies in
      each written language system as well as significant differences of activation
      likelihood between languages. Four neural systems for the phonological processing
      of Chinese characters included: (1) a left dorsal lateral frontal system at
      Brodmann area (BA) 9; (2) the dorsal aspect of left inferior parietal system; (3)
      a bilateral ventral-occipitotemporal system including portions of fusiform gyrus
      and middle occipital gyrus; and (4) a left ventral prefrontal system covering the
      superior aspect of inferior frontal gyrus. For phonological processing of written
      alphabetic words, cortical areas identified here are consistent with the three
      neural systems proposed previously in the literature: (1) a ventral prefrontal
      system involving superior portions of left inferior frontal gyrus; (2) a left
      dorsal temporoparietal system including mid-superior temporal gyri and the
      ventral aspect of inferior parietal cortex (supramarginal region); and (3) a left
      ventral occipitotemporal system. Contributions of each of these systems to
      phonological processing in reading were discussed, and a covariant learning
      hypothesis is offered to account for the findings that left middle frontal gyrus
      is responsible for addressed phonology in Chinese whereas left temporoparietal
      regions mediate assembled phonology in alphabetic languages. Language form,
      cognitive process, and learning strategy drive the development of functional
      neuroanatomy.

PMID- 15846818
TI  - Cross-cultural effect on the brain revisited: universal structures plus writing
      system variation.
AB  - Recognizing printed words requires the mapping of graphic forms, which vary with
      writing systems, to linguistic forms, which vary with languages. Using a newly
      developed meta-analytic approach, aggregated Gaussian-estimated sources (AGES;
      Chein et al. [2002]: Psychol Behav 77:635-639), we examined the neuroimaging
      results for word reading within and across writing systems and languages. To find
      commonalities, we compiled 25 studies in English and other Western European
      languages that use an alphabetic writing system, 9 studies of native Chinese
      reading, 5 studies of Japanese Kana (syllabic) reading, and 4 studies of Kanji
      (morpho-syllabic) reading. Using the AGES approach, we created meta-images within
      each writing system, isolated reliable foci of activation, and compared findings
      across writing systems and languages. The results suggest that these writing
      systems utilize a common network of regions in word processing. Writing systems
      engage largely the same systems in terms of gross cortical regions, but
      localization within those regions suggests differences across writing systems. In
      particular, the region known as the visual word form area (VWFA) shows strikingly
      consistent localization across tasks and across writing systems. This region in
      the left mid-fusiform gyrus is critical to word recognition across writing
      systems and languages.

PMID- 15846819
TI  - Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging
      studies of working memory in schizophrenia.
AB  - Although there is considerable evidence that patients with schizophrenia fail to
      activate the dorsolateral prefrontal cortex (DLPFC) to the degree seen in normal
      comparison subjects when performing working memory or executive tasks,
      hypofrontality may be coupled with relatively increased activity in other brain
      regions. However, most imaging studies of working memory in schizophrenia have
      focused on DLPFC activity. The goal of this work is to review functional
      neuroimaging studies that contrasted patients with schizophrenia and healthy
      comparison subjects during a prototypical working memory task, the n-back
      paradigm, to highlight areas of hyper- and hypoactivation in schizophrenia. We
      utilize a quantitative meta-analysis method to review 12 imaging studies where
      patients with schizophrenia were contrasted with healthy comparison subjects
      while performing the n-back paradigm. Although we find clear support for
      hypofrontality, we also document consistently increased activation in anterior
      cingulate and left frontal pole regions in patients with schizophrenia compared
      to that in controls. These data suggest that whereas reduced DLPFC activation is
      reported consistently in patients with schizophrenia relative to healthy
      subjects, abnormal activation patterns are not restricted to this region, raising
      questions as to whether the pathophysiological dysfunction in schizophrenia is
      specific to the DLPFC and about the relationship between impaired performance and
      aberrant activation patterns. The complex pattern of hyper- and hypoactivation
      consistently found across studies implies that rather than focusing on DLPFC
      dysregulation, researchers should consider the entire network of regions involved
      in a given task when making inferences about the biological mechanisms of
      schizophrenia.

PMID- 15846820
TI  - Meta-analyses of object naming: effect of baseline.
AB  - The neural systems sustaining object naming were examined using the activation
      likelihood estimation (ALE) meta-analysis approach on the results of 16
      previously published studies. The activation task in each study required subjects
      to name pictures of objects or animals, but the baseline tasks varied. Separate
      meta-analyses were carried out on studies that used: (1) high-level baselines to
      control for speech processing and visual input; and (2) low-level baselines that
      did not control for speech or complex visual processing. The results of the two
      meta-analyses were then compared directly, revealing a double dissociation in the
      activation pattern for studies using high and low baselines. To interpret the
      differential activations, we report two new functional imaging experiments. The
      aim of the first was to characterize activation differences associated with
      visual stimuli that are typically used in baseline conditions (complex visual
      features, simple structures, or fixation). The aim of the second was to classify
      object-naming regions in terms of whether they were engaged preferentially by
      semantic or phonological processes. The results reveal a remarkably precise
      correspondence between the areas identified by the meta-analyses as affected
      differentially by baseline and the areas that are affected differentially by non
      object structure, semantics or phonology. As expected, high-level baselines
      reduced object-naming activation in areas associated with the processing of
      complex visual features and speech production. In addition, high-level baselines
      increased sensitivity to activation in areas associated with semantic processing,
      visual-speech integration and response selection. For example, activation in the
      anterior temporal areas that neuropsychological studies have associated with
      semantic processing was more strongly activated in the context of high-level
      baselines. These results therefore have implications for understanding the
      convergence of functional imaging and neuropsychological findings.

PMID- 15846821
TI  - Meta-analysis of neuroimaging studies of the Wisconsin card-sorting task and
      component processes.
AB  - A quantitative meta-analysis using the activation likelihood estimation (ALE)
      method was used to investigate the brain basis of the Wisconsin Card-Sorting Task
      (WCST) and two hypothesized component processes, task switching and response
      suppression. All three meta-analyses revealed distributed frontoparietal
      activation patterns consistent with the status of the WCST as an attention
      demanding executive task. The WCST was associated with extensive bilateral
      clusters of reliable cross-study activity in the lateral prefrontal cortex,
      anterior cingulate cortex, and inferior parietal lobule. Task switching revealed
      a similar, although less robust, frontoparietal pattern with additional clusters
      of activity in the opercular region of the ventral prefrontal cortex,
      bilaterally. Response-suppression tasks, represented by studies of the go/no-go
      paradigm, showed a large and highly right-lateralized region of activity in the
      right prefrontal cortex. The activation patterns are interpreted as reflecting a
      neural fractionation of the cognitive components that must be integrated during
      the performance of the WCST.

PMID- 15846822
TI  - N-back working memory paradigm: a meta-analysis of normative functional
      neuroimaging studies.
AB  - One of the most popular experimental paradigms for functional neuroimaging
      studies of working memory has been the n-back task, in which subjects are asked
      to monitor the identity or location of a series of verbal or nonverbal stimuli
      and to indicate when the currently presented stimulus is the same as the one
      presented n trials previously. We conducted a quantitative meta-analysis of 668
      sets of activation coordinates in Talairach space reported in 24 primary studies
      of n-back task variants manipulating process (location vs. identity monitoring)
      and content (verbal or nonverbal) of working memory. We found the following
      cortical regions were activated robustly (voxelwise false discovery rate = 1%):
      lateral premotor cortex; dorsal cingulate and medial premotor cortex;
      dorsolateral and ventrolateral prefrontal cortex; frontal poles; and medial and
      lateral posterior parietal cortex. Subsidiary meta-analyses based on appropriate
      subsets of the primary data demonstrated broadly similar activation patterns for
      identity monitoring of verbal stimuli and both location and identity monitoring
      of nonverbal stimuli. There was also some evidence for distinct frontoparietal
      activation patterns in response to different task variants. The functional
      specializations of each of the major cortical components in the generic large
      scale frontoparietal system are discussed. We conclude that quantitative meta
      analysis can be a powerful tool for combining results of multiple primary studies
      reported in Talairach space. Here, it provides evidence both for broadly
      consistent activation of frontal and parietal cortical regions by various
      versions of the n-back working memory paradigm, and for process- and content
      specific frontoparietal activation by working memory.

PMID- 15846823
TI  - A comparison of label-based review and ALE meta-analysis in the Stroop task.
AB  - Meta-analysis is an important tool for interpreting results of functional
      neuroimaging studies and is highly influential in predicting and testing new
      outcomes. Although traditional label-based review can be used to search for
      agreement across multiple studies, a new function-location meta-analysis
      technique called activation likelihood estimation (ALE) offers great improvements
      over conventional methods. In ALE, reported foci are modeled as Gaussian
      functions and pooled to create a statistical whole-brain image. ALE meta-analysis
      and the label-based review were used to investigate the Stroop task in normal
      subjects, a paradigm known for its effect of producing conflict and response
      inhibition due to subjects' tendency to perform word reading as opposed to color
      naming. Both methods yielded similar activation patterns that were dominated by
      response in the anterior cingulate and the inferior frontal gyrus. ALE showed
      greater involvement of the anterior cingulate as compared to that in the label
      based technique; however, this was likely due to the increased spatial level of
      distinction allowed with the ALE method. With ALE, further analysis of the
      anterior cingulate revealed evidence for somatotopic mapping within the rostral
      and caudal cingulate zones, an issue that has been the source of some conflict in
      previous reviews of the anterior cingulate cortex.

PMID- 15846824
TI  - Involvement of the inferior frontal junction in cognitive control: meta-analyses
      of switching and Stroop studies.
AB  - There is growing evidence that a specific region in the posterior frontolateral
      cortex is involved intimately in cognitive control processes. This region,
      located in the vicinity of the junction of the inferior frontal sulcus and the
      inferior precentral sulcus, was termed the inferior frontal junction (IFJ). The
      IFJ was shown to be involved in the updating of task representations and to be
      activated commonly in a within-subject investigation of a task-switching
      paradigm, the Stroop task, and a verbal n-back task. Here, we investigate the
      involvement of the IFJ in cognitive control by employing a meta-analytic
      approach. Two quantitative meta-analyses of functional magnetic resonance imaging
      (fMRI) studies were conducted. One meta-analysis included frontal activations
      from task-switching, set-shifting, and stimulus-response (S-R) reversal studies,
      the other included frontal activations from color-word Stroop studies. Results
      showed highly significant clustering of activations in the IFJ in both analyses.
      These results provide strong evidence for the consistent involvement of the IFJ
      in both switching and Stroop paradigms. Furthermore, they support our concept of
      areal specialization in the frontolateral cortex, which posits that it is not
      only the middorsolateral part that plays an important role in cognitive control,
      but also the IFJ. Finally, our results demonstrate how quantitative meta-analyses
      can be used to test hypotheses about the involvement of specific brain regions in
      cognitive control.

PMID- 15846825
TI  - Reduction of birth prevalence rates of neural tube defects after folic acid
      fortification in Chile.
AB  - To verify whether the decreasing neural tube defects birth prevalence rates in
      Chile are due to folic acid fortification or to pre-existing decreasing trends,
      we performed a population survey using a network of Estudio Colaborativo Latino
      Americano de Malformaciones Congenitas (ECLAMC, Latin American Collaborative
      Study of Congenital Malformations) maternity hospitals in Chile, between the
      years 1982 and 2002. Within each maternity hospital, birth prevalence rates of
      spina bifida and anencephaly were calculated from two pre-fortification periods
      (1982-1989 and 1990-2000), and from one fortified period (2001-2002). There was
      no historical trend for spina bifida birth prevalence rates before folic acid
      fortification, and there was a 51% (minimum 27%, maximum 66%) decrease in the
      birth prevalence rates of this anomaly in the fortified period. The relative
      risks of spina bifida were homogeneous among hospitals in the two period
      comparisons. There was no historical trend for the birth prevalence of
      anencephaly comparing the two pre-fortified periods, but the relative risks were
      heterogeneous among hospitals in this comparison. There was a 42% (minimum 10%,
      maximum 63%) decrease in the birth prevalence rate of anencephaly in the
      fortified period as compared with the immediately pre-fortified period, with
      homogeneous relative risks among hospitals. Within the methodological constraints
      of this study we conclude that the birth prevalence rates for both spina bifida
      and anencephaly decreased as a result of folic acid fortification, without
      interference of decreasing secular trends.

PMID- 15846826
TI  - Coordinate-based voxel-wise meta-analysis: dividends of spatial normalization.
      Report of a virtual workshop.

PMID- 15846827
TI  - Stereoselective pharmacokinetics of tetrahydropalmatine after oral administration
      of (-)-enantiomer and the racemate.
AB  - Tetrahydropalmatine (THP) is a biologically active ingredient isolated from a
      traditional Chinese herb Rhizoma corydalis (yanhusuo). THP is a racemic mixture
      which contains 50% of the (+) and 50% of (-) enantiomer. The (-) enantiomer
      accounts for most of the analgesic effects. Plasma concentrations of THP
      enantiomers were analyzed by chiral high-performance liquid chromatography (HPLC)
      on a Chiralcel OJ column with quantification by UV at 230 nm. The method was used
      to determine the pharmacokinetics of THP enantiomers in rats and dogs after oral
      administration of rac-THP or (-)-THP. The pharmacokinetic profiles of the two
      enantiomers after dosing with rac-THP were significantly different both in rats
      and dogs. The mean C(max) and AUC(0-infinity) values in rats were 1.93 +/- 0.36
      microg/ml and 6.65 +/- 2.34 microg x h/ml for the (-) enantiomer, and 1.11 +/-
      0.25 microg/ml and 2.03 +/- 0.45 microg x h/ml for the (+) enantiomer. The mean
      C(max) and AUC(0-infinity) in dogs were 1.60 +/- 0.81 microg/ml and 9.88 +/- 2.58
      microg x h/ml for the (-) enantiomer, while 0.36 +/- 0.21 microg/ml and 1.22 +/-
      0.40 microg x h/ml for the (+) enantiomer. rac-THP at 40 mg/kg and (-)-THP at 20
      mg/kg had very similar plasma concentration-time profiles, and C(max), AUC(0
      infinity), and t(1/2) of the (-) enantiomer in both rats and dogs, indicating
      that the two treatments were equivalent with respect to the pharmacokinetic
      properties of the (-) enantiomer.

PMID- 15846828
TI  - Selective meta-deprotonation of toluene by using alkali-metal-mediated
      magnesiation.

PMID- 15846829
TI  - Studies toward the synthesis of azadirachtin, part 1: total synthesis of a fully
      functionalized ABC ring framework and coupling with a norbornene domain.

PMID- 15846831
TI  - Calix[4]pyrrole: an old yet new ion-pair receptor.

PMID- 15846835
TI  - Conjugated oligomers with terminal donor-acceptor substitution.
AB  - Conjugated oligomers represent a prominent class of compounds from a viewpoint of
      their theory, synthesis, and applications in materials science. Push-pull
      substitution with an electron donor D at one end of the conjugation and an
      electron acceptor A at the other end results in them having outstanding optical
      and electronical properties. This Review highlights fundamental synthetic
      strategies for the preparation of such oligomers with n repeat units (n=1, 2, 3,
      4, ..) and the rules that govern their linear and nonlinear optical properties
      (absorption, frequency doubling and tripling). The unification of chemical,
      physical, and theoretical aspects with an interdisciplinary image of this class
      of compounds is attempted herein.

PMID- 15846836
TI  - Sensitization of near-infrared-emitting lanthanide cations in solution by
      tropolonate ligands.

PMID- 15846837
TI  - A "de-streaking" method for two-dimensional electrophoresis using the reducing
      agent tris(2-carboxyethyl)-phosphine hydrochloride and alkylating agent
      vinylpyridine.
AB  - Optimal isoelectric focusing in the alkaline region remains a challenge in two
      dimensional gel electrophoresis (2-DE), though various attempts had been made to
      reduce basic end streaking. The present study reports the application of a novel
      reduction and alkylation step prior to 2-DE analysis using tris(2-carboxyethyl)
      phosphine hydrochloride as a reducing agent and vinylpyridine as an alkylating
      agent. This simple sample preparation approach effectively eliminates basic end
      streaks, thereby enabling the analysis and identification of more protein spots
      resolved by 2-DE.

PMID- 15846839
TI  - Shotgun proteome analysis of protein cleavage in apoptotic cells.
AB  - A new shotgun proteomics approach was employed to identify degraded proteins.
      Jurkat T-cells were induced to undergo apoptosis by Fas (CD95/Apo-1) stimulation.
      The proteins were separated by large (30 cm) sodium dodecyl sulphate
      polyacrylamide gel electrophoresis and identified by liquid chromatography-tandem
      mass spectrometry after digestion of 100 gel slices with trypsin. The molecular
      masses of the individual gel slices were calculated through the known theoretical
      masses of the identified proteins. Proteins were defined as degradation
      candidates if either the empirical determined molecular mass was at most 80% of
      the theoretical value, or if proteins were identified in clearly different gel
      slices. In this manner, the degradation of 11 already identified apoptosis
      modified proteins was confirmed and nine until now unknown degradation candidate
      proteins identified. Degradation during apoptosis must be verified by additional
      techniques such as in vitro caspase assays as shown for nucleolin and Rho GDI 2.
      The results presented confirm the suitability of a shotgun approach for the
      identification of putative protease targets.

PMID- 15846840
TI  - PROTICdb: a web-based application to store, track, query, and compare plant
      proteome data.
AB  - PROTICdb is a web-based application, mainly designed to store and analyze plant
      proteome data obtained by two-dimensional polyacrylamide gel electrophoresis (2-D
      PAGE) and mass spectrometry (MS). The purposes of PROTICdb are (i) to store,
      track, and query information related to proteomic experiments, i.e., from tissue
      sampling to protein identification and quantitative measurements, and (ii) to
      integrate information from the user's own expertise and other sources into a
      knowledge base, used to support data interpretation (e.g., for the determination
      of allelic variants or products of post-translational modifications). Data
      insertion into the relational database of PROTICdb is achieved either by
      uploading outputs of image analysis and MS identification software, or by filling
      web forms. 2-D PAGE annotated maps can be displayed, queried, and compared
      through a graphical interface. Links to external databases are also available.
      Quantitative data can be easily exported in a tabulated format for statistical
      analyses. PROTICdb is based on the Oracle or the PostgreSQL Database Management
      System and is freely available upon request at the following URL:
      http://moulon.inra.fr/ bioinfo/PROTICdb.

PMID- 15846841
TI  - Recent developments in structural proteomics for protein structure determination.
AB  - The major challenges in structural proteomics include identifying all the
      proteins on the genome-wide scale, determining their structure-function
      relationships, and outlining the precise three-dimensional structures of the
      proteins. Protein structures are typically determined by experimental approaches
      such as X-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy.
      However, the knowledge of three-dimensional space by these techniques is still
      limited. Thus, computational methods such as comparative and de novo approaches
      and molecular dynamic simulations are intensively used as alternative tools to
      predict the three-dimensional structures and dynamic behavior of proteins. This
      review summarizes recent developments in structural proteomics for protein
      structure determination; including instrumental methods such as X-ray
      crystallography and NMR spectroscopy, and computational methods such as
      comparative and de novo structure prediction and molecular dynamics simulations.

PMID- 15846842
TI  - Chronically inflamed synovium from spondyloarthropathy and rheumatoid arthritis
      investigated by protein expression profiling followed by tandem mass
      spectrometry.
AB  - We investigated the cytosolic proteome of inflamed synovial tissue by
      hierarchical clustering analysis and validated the feasibility of this proteome
      analysis by identifying proteins that were differentially expressed between
      rheumatoid arthritis (RA), spondyloarthropathy (SpA), and osteoarthritis (OA).
      Synovial biopsy samples were obtained from 18 patients undergoing needle
      arthroscopy for knee synovitis associated with RA (n = 6) and SpA (n = 6), and
      for joint effusion of the knee associated with OA (n = 6). Cytosolic proteins
      were extracted from the tissue and subjected to two-dimensional gel
      electrophoresis. Protein expression patterns were statistically analyzed and used
      for hierarchical cluster analysis. Proteins of interest were independently
      identified by matrix-assisted laser desorption/ionization- and electrospray
      ionization-mass spectrometry. Hierarchical cluster analysis of the complete match
      set, containing 640 spots, remarkably segregated SpA from RA and OA. Next, we
      used a subset of spots that was statistically, differentially expressed (P <
      0.01), between RA and SpA, SpA and OA, or RA and OA, in both Student's t-test and
      Mann-Whitney U-test. The dendrograms revealed distinct clustering of RA versus
      SpA and RA versus OA. Spots that were differentially expressed between the groups
      were identified by tandem mass spectrometry. Fructose bisphosphate aldolase A and
      alpha-enolase showed higher expression levels in SpA than in OA (P < 0.01).
      Calgranulin A myeloid related protein-8 (MRP-8) was markedly up-regulated in RA
      and SpA patients in comparison to OA patients where this spot was below detection
      limit. The analysis of the cytosolic proteome of synovial tissue is a useful
      approach to identify disease-associated proteins in chronic inflammatory
      arthritis.

PMID- 15846843
TI  - Mapping of phosphorylation sites of nuclear corepressor receptor interacting
      protein 140 by liquid chromatography-tandem mass spectroscopy.
AB  - Receptor interacting protein (RIP140) is a versatile coregulator for many nuclear
      receptors and transcription factors. Analysis by liqid chromatography tandem mass
      spectroscopy led to the identification of 11 phosphopeptides from tryptic digests
      of His6-RIP140 purified from Sf21 insect cells. No phosphopeptides were detected
      on RIP140 expressed in E. coli in a parallel experiment, suggesting that RIP140
      phosphorylation occurred specifically only in eukaryotic cells. The tandem mass
      spectra of the precursor ions of the phosphopeptides were analyzed to map the
      exact phosphorylation sites on RIP140. All the phosphopeptides displayed intact
      phosphate containing y- or b-ion signals along with their beta-eliminated product
      ions, due to neutral loss of phosphoric acid. Phosphorylation occurred
      specifically on nine serine and a single threonine residues, including Ser-104,
      Thr-207, Ser-358, Ser-380, Ser-488, Ser-519, Ser-531, Ser-543, Ser-672, and Ser
      1003. No tyrosine phosphorylation was found. These data suggested that the
      central region of RIP140, one major repressive domain, was extensively modified
      by phosphorylation. These phosphorylation sites can be the targets in future
      studies addressing post-translational modification of RIP140 with regards to its
      biological activities.

PMID- 15846844
TI  - Proteomic profiling of cellular proteins interacting with the hepatitis C virus
      core protein.
AB  - Hepatitis C virus (HCV) is a causative agent of chronic hepatitis and
      hepatocellular carcinoma. The core protein of HCV packages the viral RNA genome
      to form a nucleocapsid. In addition to its function as a structural protein, core
      protein is involved in regulation of cellular transcription, virus-induced
      transformation, and pathogenesis. To gain insights into cellular functions of the
      core protein by identification of cellular proteins interacting with the core
      protein, we employed a proteomic approach. Hepatocytes soluble cytoplasmic
      proteins were applied to the core proteins immobilized on Ni-nitrilotriacetic
      resin and total bound cellular proteins were resolved by 2-DE. Analyses of
      interacting proteins by matrix-assisted laser desorption/ionization-time of
      flight mass spectrometry allowed identification of 14 cellular proteins binding
      to the core protein. These proteins include DEAD-box polypeptide 5, similar in
      function to a known protein identified previously by yeast two-hybrid screening
      and 13 newly identified cellular proteins. Interestingly, nine protein spots were
      identified as intermediate microfilament proteins, including cytokeratins (five
      spots for cytokeratin 8, two for cytokeratin 19, and one for cytokeratin 18) and
      vimentin. Cytokeratin 8 and vimentin, which were previously shown to be involved
      in the infection processes of other viruses, were further analyzed to confirm
      their in vivo interactions with the core protein by immunoblotting and
      immunofluorescence microscopy. We discuss the functional implications of the
      interactions of the core protein with newly identified cellular proteins in HCV
      infection and pathogenesis.

PMID- 15846847
TI  - South African firm gets US approval for AIDS drugs.

PMID- 15846845
TI  - Evidence for lymphangiogenesis and its prognostic implications in head and neck
      squamous cell carcinoma.
AB  - Lymph node metastasis is a frequent reason for adverse clinical outcome in many
      epithelial neoplasms, including head and neck squamous cell carcinoma. The
      mechanisms underlying the capability of epithelial neoplasms to metastasize via
      lymphatic vessels have not yet been fully elucidated. There is great debate about
      whether cancer cells can metastasize by expansion and invasion of pre-existing
      peritumoral lymphatics or by the formation and invasion of new lymphatics within
      tumours (lymphangiogenesis). In order to investigate this issue, we examined 81
      tissue specimens from patients with head and neck squamous cell carcinoma, using
      immunostaining for the specific lymphatic endothelium marker podoplanin, and
      assessed intratumoral and peritumoral lymphatic density. We also quantified
      lymphatic invasion and examined the possible associations of all the above
      parameters with clinicopathological features and outcome. Finally, we used double
      staining with podoplanin and the cell proliferation marker Ki-67 in order to
      evaluate lymphangiogenesis. High intratumoral and peritumoral lymphatic density
      were both significantly associated with the presence of lymph node metastasis at
      the time of diagnosis (chi2 test, p < 0.001 and p = 0.007, respectively) and
      there was a significant correlation between high intratumoral lymphatic density
      and lymphatic invasion. Patients with higher intratumoral lymphatic density
      exhibited shorter overall survival (log rank p < 0.001) and this correlation
      remained significant after multivariate analysis (Cox p = 0.04), indicating that
      intratumoral lymphatic density is an independent prognostic factor for mortality.
      Peritumoral lymphatic density had no influence on outcome. Double staining
      revealed the existence of proliferating intratumoral lymphatics, in which tumour
      emboli were occasionally observed. These results indicate that lymphangiogenesis
      indeed occurs in head and neck squamous cell carcinoma; that newly formed vessels
      are targets of invasion by cancer cells; and that intratumoral lymphatic density
      might be used as a criterion to separate patients at higher risk of an adverse
      clinical outcome.

PMID- 15846848
TI  - Averting drug resistance while preventing MTCT.

PMID- 15846849
TI  - Cranberry juice and urinary tract infections.

PMID- 15846850
TI  - More on nighttime leg cramps.

PMID- 15846851
TI  - By the way, doctor. I'm 86, and someone told me that I"m no longer in danger of
      getting Alzheimer's disease. My memory isn't quite what it was, though. Would
      Alzheimer's medicines help?

PMID- 15846852
TI  - By the way, doctor. In January, you wrote about an ultra-low dose estrogen patch
      that helps prevent osteoporosis. Is it available to the public?

PMID- 15846853
TI  - Perfect practice makes perfect.

PMID- 15846856
TI  - An elderly man with immunosuppression, shortness of breath, and eosinophilia.

PMID- 15846854
TI  - Effects of COMT genotype on behavioral symptomatology in the 22q11.2 Deletion
      Syndrome.
AB  - The 22q11.2 Deletion Syndrome (DiGeorge/velocardiofacial syndrome) is associated
      with elevated rates of psychosis, and is also characterized by severe attentional
      difficulties and executive dysfunction. Behavioral manifestations of this
      syndrome could result from haploinsufficiency of the catechol-O-methyltransferase
      (COMT) gene, located within the 22q11 region. The goal of the present study was
      to examine COMT genotype in relation to behavioral symptomatology in this
      syndrome. Val158/108Met was genotyped in 38 patients (16 Met/-, 22 Val/-) with
      confirmed 22q11.2 deletions who had received the Child Behavior Checklist (CBCL)
      as part of a comprehensive evaluation. Results indicated that the Val genotype
      was associated with significantly greater internalizing and externalizing
      behavioral symptomatology in children with 22q11.2 deletions. Val allele status
      was associated with a greater-than-four-fold increase in risk for clinically
      significant behavior problems in children with this syndrome. These data are
      consistent with previous findings of increased psychopathology associated with
      the Val genotype in normal individuals and suggest that a functional genetic
      polymorphism in the 22q11 region may influence behavior in individuals with COMT
      haploinsufficiency.

PMID- 15846857
TI  - Clopidogrel versus aspirin and esomeprazole to prevent recurrent bleeding.

PMID- 15846858
TI  - Clopidogrel versus aspirin and esomeprazole to prevent recurrent bleeding.

PMID- 15846859
TI  - Outcomes associated with a trial of labor after prior cesarean delivery.

PMID- 15846860
TI  - Outcomes associated with a trial of labor after prior cesarean delivery.

PMID- 15846861
TI  - Outcomes associated with a trial of labor after prior cesarean delivery.

PMID- 15846862
TI  - Case 35-2004: nephrogenic fibrosing dermopathy.

PMID- 15846864
TI  - [The 78th general meeting of Japanese Leprosy Association. Aomori, Japan. May 18
      20, 2005. Abstracts].

PMID- 15846863
TI  - [The presence of Mycoplasma hominis and Ureaplasma urealyticum in the cervical
      canal of uterus].
AB  - OBJECTIVES: Mycoplasma hominis and Ureaplasma species are common commensal
      inhabitants of the lower genitourinary tract in adolescents and adults who are
      sexually active. A lot of authors points out that these microorganisms can play
      an important role in pathology of genital tract like pelvic inflammatory disease,
      sterility or non-gonococcal urethritis. MATERIALS AND METHODS: In the study
      samples from cervical canal of the uterus were obtained from 222 women. The first
      group consist of 132 women who were examined in II Gynecological Clinic in
      Wroclaw for different, probably infectious, gynecological pathologies (adnexitis,
      sterility, bacterial vaginosis). 90 women without infectious diseases were in a
      control group. All swabs taken from cervix were tested for Mycoplasma hominis and
      Ureaplasma urealyticum. RESULTS: The prevalence of Ureaplasma urealyticum was
      31.8% in the first tested group (42 of 132 women were positive) and 8.8% in
      control group (8 of 90 were positive). 3% (4 of 132) of patients were positive to
      Mycoplasma hominis in the first group and only 1.1% (1 of 90) in a control group.
      CONCLUSIONS: Ureaplasma urealyticum was found most often in such genital tract
      pathologies like acute or recurrent adnexitis, sterility or bacterial vaginosis.
      No statistically significant correlation was found between the age of the
      patients and the incidence of mycoplasmas.

PMID- 15846865
TI  - [Abecedary of the "Annales". Part 2].
AB  - The terms included and detailed in the present part are: Subgroup analysis,
      analysis of variance, Blind.

PMID- 15846866
TI  - Exceptional matters: clinical research from bedside to bench.

PMID- 15846867
TI  - Synthesis and characterization of novel 6-fluoro-4-piperidinyl-1,2-benzisoxazole
      amides and 6-fluoro-chroman-2-carboxamides: antimicrobial studies.
AB  - Novel derivatives of 6-fluoro-4-piperidinyl-1,2-benzisoxazole amides 4(I-VI) were
      obtained by the condensation of different acid chlorides with 6-fluoro-3
      piperidin-4yl-benzo[d]isoxazole. Also, 6-fluoro-chroman-2-carboxamides 6(I-III)
      were synthesized by using nebulic acid chloride with different amines in presence
      of triethylamine as acid scavenger and dichloroethane as solvent. The synthesized
      compounds were characterized by IR, 1H NMR, and CHN analysis. These molecules
      were evaluated for their efficacy as antimicrobials in vitro by disc diffusion
      and microdilution method against pathogenic strains such as Bacillus substilis,
      Escherichia coli, Pseudomonas fluorescens, Xanthomonas campestris pvs, X. oryzae,
      Aspergillus niger, A. flavus, Fusarium oxysporum, Trichoderma species, F.
      monaliforme, and Penicillum species. Compounds 4I, 4IV, 4V, 6I, 6II and 6III
      showed better inhibitory activity than compared to standard drugs. Among these
      compounds, 4IV and 6III showed potent inhibitory activity against all the strains
      and found to be nonstrain dependent. The title compounds represent a novel class
      of potent antimicrobial agents.

PMID- 15846868
TI  - Testing the limits of freedom of contract: the commercialization of reproductive
      materials and services.
AB  - This article examines the cases for and against commercializing, or
      "commodifying," reproductive materials and services. Using a supply/demand third
      party framework, three basic scenarios in which commercial-exchange relationships
      may be possible--exchange of gametes and zygotes, exchange of gestational
      services, and exchange of fetal material--and the major parties of interest, or
      stakeholders, are identified. The study sketches the liberal, essentialist, and
      radical contingency theories that shape the debate over the commercialization of
      reproductive materials and services. The article then attempts to derive some
      basic governing principles that reflect as much common ground as possible amongst
      these various normative perspectives, while recognizing that complete
      reconciliation is impossible. Taken together, these principles are designed to
      reflect a strategy of "constrained commodification," where commercialization or
      commodification, that is, financial remuneration, plays a relatively neutral role
      in the utilization of reproductive materials and services. In light of these
      principles, the article concludes by sketching legal and regulatory regimes with
      respect to the exchange of gametes and zygotes, gestational services, and fetal
      tissue.

PMID- 15846869
TI  - Nuclear markers confirm taxonomic status and relationships among highly
      endangered and closely related right whale species.
AB  - Right whales (genus: Eubalaena) are among the most endangered mammals, yet their
      taxonomy and phylogeny have been questioned. A phylogenetic hypothesis based on
      mitochondrial DNA (mtDNA) variation recently prompted a taxonomic revision,
      increasing the number of right whale species to three. We critically evaluated
      this hypothesis using sequence data from 13 nuclear DNA (nuDNA) loci as well as
      the mtDNA control region. Fixed diagnostic characters among the nuclear markers
      strongly support the hypothesis of three genetically distinct species, despite
      lack of any diagnostic morphological characters. A phylogenetics analysis of all
      data produced a strict consensus cladogram with strong support at nodes that
      define each right whale species as well as relationships among species. Results
      showed very little conflict among the individual partitions as well as congruence
      between the mtDNA and nuDNA datasets. These data clearly demonstrate the strength
      of using numerous independent genetic markers during a phylogenetics analysis of
      closely related species. In evaluating phylogenetic support contributed by
      individual loci, 11 of the 14 loci provided support for at least one of the nodes
      of interest to this study. Only a single marker (mtDNA control region) provided
      support at all four nodes. A study using any single nuclear marker would have
      failed to support the proposed phylogeny, and a strong phylogenetic hypothesis
      was only revealed by the simultaneous analysis of many nuclear loci. In addition,
      nu DNA and mtDNA data provided complementary levels of support at nodes of
      different evolutionary depth indicating that the combined use of mtDNA and nuDNA
      data is both practical and desirable.

PMID- 15846870
TI  - Walter Ellis Sistrunk (1880-1933).

PMID- 15846871
TI  - George Washington Crile.

PMID- 15846872
TI  - Nanomaterial-based electrochemical biosensors.
AB  - The unique properties of nanoscale materials offer excellent prospects for
      interfacing biological recognition events with electronic signal transduction and
      for designing a new generation of bioelectronic devices exhibiting novel
      functions. In this Highlight I address recent research that has led to powerful
      nanomaterial-based electrical biosensing devices and examine future prospects and
      challenges. New nanoparticle-based signal amplification and coding strategies for
      bioaffinity assays are discussed, along with carbon-nanotube molecular wires for
      achieving efficient electrical communication with redox enzyme and nanowire-based
      label-free DNA sensors.

PMID- 15846873
TI  - A tour of U.K. healthcare.

PMID- 15846874
TI  - Characterization of microbial and chemical composition of shuttle wet waste with
      permanent gas and volatile organic compound analyses.
AB  - Solid-waste treatment in space for Advanced Life Support, ALS, applications
      requires that the material can be safely processed and stored in a confined
      environment. Many solid-wastes are not stable because they are wet (40-90%
      moisture) and contain levels of soluble organic compounds that can contribute to
      the growth of undesirable microorganisms with concomitant production of noxious
      odors. In the absence of integrated Advanced Life Support systems on orbit,
      permanent gas, trace volatile organic and microbiological analyses were performed
      on crew refuse returned from the volume F "wet" trash of three consecutive
      Shuttle missions (STS-105, 109, and 110). These analyses were designed to
      characterize the short-term biological stability of the material and assess
      potential crew risks resulting from microbial decay processes during storage.
      Waste samples were collected post-orbiter landing and sorted into packaging
      material, food waste, toilet waste, and bulk liquid fractions deposited during
      flight in the volume F container. Aerobic and anaerobic microbial loads were
      determined in each fraction by cultivation on R2A and by acridine orange direct
      count (AODC). Dry and ash weights were performed to determine both water and
      organic content of the materials. Experiments to determine the aerobic and
      anaerobic biostability of refuse stored for varying periods of time were
      performed by on-line monitoring of CO2 and laboratory analysis for production of
      hydrogen sulfide and methane. Volatile organic compounds and permanent gases were
      analyzed using EPA Method TO15 by USEPA et al. [EPA Method TO15, The
      Determination of Volatile Organic Compounds (VOCs) in Ambient Air using SUMMA,
      Passivated Canister Sampling and Gas Chromatographic Analysis,1999] with gas
      chromatography/mass spectrometry and by gas chromatography with selective
      detectors. These baseline measures of waste stream content, labile organics, and
      microbial load in the volume F Shuttle trash provide data for waste subsystem
      analysis and atmospheric management within the ALS Project.

PMID- 15846875
TI  - [The 26th report on survey of the adverse Reaction of radiopharmaceuticals (the
      29th Survey in 2003)].

PMID- 15846876
TI  - Technical review of the Laboratory Biosphere closed ecological system facility.
AB  - Laboratory Biosphere is a 40 m3 closed life system that commenced operation in
      May 2002. Light is from 12,000 W of high pressure sodium lamps over planting beds
      with 5.37 m2 of soil. Water is 100% recycled by collecting condensate from the
      temperature and humidity control system and mixing with leachate collected from
      under the planting beds. Atmospheric leakage was estimated during the first
      closure experiment to be 0.5-1% per day in general plus about 1% for each usage
      of the airlock door. The first trial run of 94 days was with a soybean crop grown
      from seeds (May 17, 2002) to harvest (August 14, 2002) plus 5 days of post
      harvest closure. The focus of this initial trial was system testing to confirm
      functionality and identify any necessary modifications or improvements. This
      paper describes the organizational and physical features of the Laboratory
      Biosphere.

PMID- 15846877
TI  - The MELISSA pilot plant facility as as integration test-bed for advanced life
      support systems.
AB  - The different advances in the Micro Ecological Life Support System Alternative
      project (MELISSA), fostered and coordinated by the European Space Agency, as well
      as in other associated technologies, are integrated and demonstrated in the
      MELISSA Pilot Plant laboratory. During the first period of operation, the
      definition of the different compartments at an individual basis has been
      achieved, and the complete facility is being re-designed to face a new period of
      integration of all these compartments. The final objective is to demonstrate the
      potentiality of biological systems such as MELISSA as life support systems. The
      facility will also serve as a test bed to study the robustness and stability of
      the continuous operation of a complex biological system. This includes testing of
      the associated instrumentation and control for a safe operation, characterization
      of the chemical and microbial safety of the system, as well as tracking the
      genetic stability of the microbial strains used. The new period is envisaged as a
      contribution to the further development of more complete biological life support
      systems for long-term manned missions, that should be better defined from the
      knowledge to be gained from this integration phase. This contribution summarizes
      the current status of the Pilot Plant and the planned steps for the new period.

PMID- 15846878
TI  - Operation of magnetically assisted fluidized beds in microgravity and variable
      gravity: experiment and theory.
AB  - The conversion of solid waste into useful resources in support of long duration
      manned missions in space presents serious technological challenges. Several
      technologies, including supercritical water oxidation, microwave powered
      combustion and fluidized bed incineration, have been tested for the conversion of
      solid waste. However, none of these technologies are compatible with microgravity
      or hypogravity operating conditions. In this paper, we present the gradient
      magnetically assisted fluidized bed (G-MAFB) as a promising operating platform
      for fluidized bed operations in the space environment. Our experimental and
      theoretical work has resulted in both the development of a theoretical model
      based on fundamental principles for the design of the G-MAFB, and also the
      practical implementation of the G-MAFB in the filtration and destruction of solid
      biomass waste particles from liquid streams.

PMID- 15846879
TI  - The minimal cost of life in space.
AB  - The cost of keeping people alive in space is assessed from a theoretical
      viewpoint and using two actual designs for plant growth systems. While life
      support is theoretically not very demanding, our ability to implement life
      support is well below theoretical limits. A theoretical limit has been calculated
      from requirements and the state of the art for plant growth has been calculated
      using data from the BIO-Plex PDR and from the Cornell CEA prototype system. The
      very low efficiency of our current approaches results in a high mission impact,
      though we can still see how to get a significant reduction in cost of food when
      compared to supplying it from Earth. Seeing the distribution of costs should
      allow us to improve our current designs.

PMID- 15846880
TI  - Stoichiometric constraints and complete closure of long-term life support
      systems.
AB  - High closure of matter recycling is an obvious requirement for long-term life
      support systems (LSS). Biological species are obligate components of the LSS
      since physical/chemical components are not able yet to provide food for crew.
      However including biological species into LSS is difficult due to specific
      stoichiometric configuration of their inputs and outputs. Formally the problem is
      to estimate the ability for given set of species to provide complete closure of
      LSS. Two possible models of metabolism organization can be considered: rigid and
      flexible ones. Stoichiometric analyses showed that the rigid metabolism case is
      not typical and takes place with very specific requirements. The flexible
      metabolic model can be applied to describing wide range of systems. Some formal
      indications of ability to provide complete closure and stationarity of LSS state
      are considered in the paper. These indications establish some constraints on the
      form of mathematical models intended to describe artificial and natural
      ecological systems.

PMID- 15846881
TI  - Examination of a smallest CELSS (microcosm) through an individual-based model
      simulation.
AB  - Research of the effect of space environment on an ecosystem consisting of plants
      and animals is essential when they are to be positively used in space. Although
      there have been experiments on various organisms under space environment in the
      past, they mainly studied the effect of space environment on an individual
      organism or a single species. Microcosm is drawing attention as an experimental
      material of an ecosystem consisting of multiple species. The object in this
      research is to understand the nature of this network system called ecosystem.
      Thus, a mixed microorganism culturing system consisting of three types of
      microorganisms which form a minimum food chain system as a closed ecosystem
      (chlorella as the producer, bacteria as the decomposer, and rotifer as the
      consumer) was taken for the subject, on which to research the universal
      characteristics of ecosystems. From the results of experiments under the
      terrestrial environment, formation of colonies, which is an ecological structure,
      has been observed at its mature stage. The organisms form an optimal substance
      circulation system. Therefore, formation of colonies in simulation models is
      important. Many attempts have been made to create ecosystem models. For example,
      the Lotka-Volterra model forms a simultaneous equation with the differential
      equation expressing predator and prey relationship and many numerical
      calculations have been conducted on various ecosystems based on expanded L-V
      models. Conventionally, these top-down methods have been used. However, since
      this method only describes the average concentration of organisms that are
      distributed uniformly throughout the system and cannot express the spatial
      structure of the system, it was difficult to express ecosystem structures like
      colonies and density distributions. In actual ecosystems, there is heterogeneity
      in the number of individuals and in substance density, and this is thought to
      have great significance in ecosystems. Consequently, an individual-based model
      was used that applies rules to predator-prey relationship, suppression,
      production, self suppression, etc., of each species. It enabled the emergence of
      the overall system only by its local rules, and it was possible to reproduce
      colony generation. In addition, the transition and the ratio of populations for
      each species match well with experimental results.

PMID- 15846882
TI  - Using explanatory crop models to develop simple tools for Advanced Life Support
      system studies.
AB  - System-level analyses for Advanced Life Support require mathematical models for
      various processes, such as for biomass production and waste management, which
      would ideally be integrated into overall system models. Explanatory models (also
      referred to as mechanistic or process models) would provide the basis for a more
      robust system model, as these would be based on an understanding of specific
      processes. However, implementing such models at the system level may not always
      be practicable because of their complexity. For the area of biomass production,
      explanatory models were used to generate parameters and multivariable polynomial
      equations for basic models that are suitable for estimating the direction and
      magnitude of daily changes in canopy gas-exchange, harvest index, and production
      scheduling for both nominal and off-nominal growing conditions.

PMID- 15846883
TI  - Model implementation for dynamic computation of system cost for advanced life
      support.
AB  - Life support system designs for long-duration space missions have a multitude of
      requirements drivers, such as mission objectives, political considerations, cost,
      crew wellness, inherent mission attributes, as well as many other influences.
      Evaluation of requirements satisfaction can be difficult, particularly at an
      early stage of mission design. Because launch cost is a critical factor and
      relatively easy to quantify, it is a point of focus in early mission design. The
      method used to determine launch cost influences the accuracy of the estimate.
      This paper discusses the appropriateness of dynamic mission simulation in
      estimating the launch cost of a life support system. This paper also provides an
      abbreviated example of a dynamic simulation life support model and possible ways
      in which such a model might be utilized for design improvement.

PMID- 15846884
TI  - Engineering concepts for inflatable Mars surface greenhouses.
AB  - A major challenge of designing a bioregenerative life support system for Mars is
      the reduction of the mass, volume, power, thermal and crew-time requirements.
      Structural mass of the greenhouse could be saved by operating the greenhouse at
      low atmospheric pressure. This paper investigates the feasibility of this
      concept. The method of equivalent system mass is used to compare greenhouses
      operated at high atmospheric pressure to greenhouses operated at low pressure for
      three different lighting methods: natural, artificial and hybrid lighting.

PMID- 15846885
TI  - Developing a vitamin greenhouse for the life support system of the International
      Space Station and for future interplanetary missions.
AB  - In order to evaluate the effects of gravity on growing plants, we conducted
      ground based long-term experiments with dwarf wheat, cultivar Apogee and Chinese
      cabbage, cultivar Khibinskaya. The test crops had been grown in overhead position
      with HPS lamp below root module so gravity and light intensity gradients had been
      in opposite direction. Plants of the control crop grew in normal position under
      the same lamp. Both crops were grown on porous metallic membranes with stable -1
      kPa matric potential on their surface. Results from these and other studies
      allowed us to examine the differences in growth and development of the plants as
      well as the root systems in relation to the value of the gravity force influence.
      Dry weight of the roots from test group was decreased in 2.5 times for wheat and
      in 6 times - at the Chinese cabbage, but shoot dry biomass was practically same
      for both test and control versions. A harvest index of the test plants increased
      substantially. The data shows, that development of the plants was essentially
      changed in microgravity. The experiments in the space greenhouse Svet aboard the
      Mir space station proved that it is possible to compensate the effects of
      weightlessness on higher plants by manipulating gradients of environmental
      parameters (i.e. photon flux, matric potential in the root zone, etc.). However,
      the average productivity of Svet concerning salad crops even in ground studies
      did not provide more than 14 g fresh biomass per day. This does not provide a
      sufficient level of supplemental nutrients to the crew of the ISS. A cylindrical
      design of a space plant growth chamber (SPGC) allows for maximal productivity in
      presence of very tight energy and volume limitations onboard the ISS and provides
      a number of operational advantages. Productivity from this type of SPGF with a
      0.5 kW energy utilization when salad growing would provide approximately 100 g of
      edible biomass per day, which would almost satisfy requirements for a crew of two
      in vitamin C and carotene and partly vitamin B group as well as rough fiber.

PMID- 15846886
TI  - Studies on the spring rise phenomenon in ovine helminthiasis. I. Spring rise in
      stabled sheep.
AB  - Serial ova count studies were conducted to determine some of the characteristics
      of the spring rise in faecal shedding of nematode ova by parasitized sheep in
      flocks in the Montreal area. It was discovered that substantial spring rises
      occurred in most ewes following their lambing but that great variation existed in
      the magnitude, duration, and pattern of the rises. Although rams did not display
      increased ova counts, a slight but well-defined rise developed in one unbred ewe.
      Larval studies in ewes parasitized by a variety of nematode species, revealed
      that Haemonchus contortus was the major contributor to the spring rise in faecal
      ova output. Preparturient treatment of ewes with thiabendazole(1), at the rate of
      100 mg./kg. of body weight, suppressed spring rise but failed to arrest
      completely the faecal shedding of nematode ova.

PMID- 15846887
TI  - A selective-differential medium for detection of Streptococcus agalactiae.
AB  - A practical culture medium which allows direct plating of milk samples for
      detection and differentiation of Streptococcus agalactiae within 48 hours is
      described. Most other micro-organisms likely to be present in these samples are
      inhibited. Although some strains of Staphylococcus species and ofStreptococcus
      faecalis are able to grow, they may be differentiated on the basis of reaction in
      the medium surrounding the colonies.

PMID- 15846888
TI  - A method for cerebroventricular cannulation of the rat.
AB  - A convenient technique is described for the preparation and surgical implantation
      of permanent cannulae into the lateral ventricles of the rat brain, as well as a
      method for radiographic confirmation of the location of the implanted cannula.
      The modified implantation method described is simple, rapid and has produced low
      mortality in the surgically altered animals.

PMID- 15846889
TI  - A histological study of the effects of enzootic abortion of ewes virus in the
      lactating bovine mammary gland.
AB  - Inoculation of the udders of cows with the virus of enzootic abortion of ewes
      resulted in a severe acute mastitis. The mastitis was characterized clinically by
      pyrexia, anorexia, decreased milk production, swelling and marked alteration in
      the physical quality of the milk. The basic lesion was necrosis of alveolar and
      duct epithelial cells. Virus particles were demonstrated in all levels of the
      mammary gland three days after inoculation illustrating the rapid spread of the
      agent. Cells resembling Reed-Sternberg cells and similar to those seen in
      experimental mastitis produced by the virus of infectious bovine rhinotracheitis
      were seen in tissues collected six and nine days after inoculation.

PMID- 15846890
TI  - Experimental bluetongue disease in white-tailed deer.
AB  - Nine white-tailed deer and six sheep were experimentally exposed to the
      California BTV-8 strain of bluetongue virus. The infections were fatal for seven
      of the nine deer. An additional deer died from exposure to an isolate of
      bluetongue virus from bighorn sheep. Clinical signs and lesions of bluetongue in
      deer were described. The incubation period, signs and lesions of bluetongue and
      epizootic hemorrhagic disease of deer appear to be similar. Virus isolations were
      made from the blood and a variety of tissues of exposed deer and identified as
      bluetongue virus. Neutralizing antibodies were detected in all of the
      convalescent sera.

PMID- 15846891
TI  - Staphylococcal arthritis in a white-tailed deer (Odocoileus virginianus).
AB  - A five and one-half year old deer (Odocoileus virginianus) developed an
      ankylosing periarticular hypertrophic arthritis due to a coagulase positive
      staphylococcus infection. Complete encasement of the tibio-tarsal (hock) joints
      with a hypertrophic, and porous osseous mass had occurred with complete loss of
      articular cartilage. The pathologic alterations of the tissues are compared to
      those occurring in swine due to Erysipelothrix insidiosa infection which produces
      a rheumatoid-like arthritis.

PMID- 15846892
TI  - The antibody response in pigs inoculated with attenuated African swine fever
      virus.
AB  - Pigs were inoculated with a modified isolate of African swine fever virus (ASFV).
      Complement-fixing (CF) and agar gel diffusion precipitin (AGDP) antibodies could
      be detected in the serums of most pigs from 14-days postinoculation (DPI) until
      their immunity was challenged with virulent ASFV at 117 DPI. Reductive cleavage
      with 2-mercaptoethanol showed that serums collected at 14 to 35 DPI contained 19S
      antibody, but that the 7S antibody was dominant at 35 and 117 DPI. This
      distribution of antibody was confirmed by sucrose-gradient centrifugation. Nearly
      all of the early serums also contained 7S antibodies which fixed complement and
      reacted in the AGDP test. Pigs whose serums contained both CF and AGDP antibodies
      at time of challenge failed to develop acute disease while pigs without CF
      antibodies were usually not protected. Pigs surviving challenge with virulent
      virus showed no increase in antibody titers, or reversion to 19S antibody.

PMID- 15846893
TI  - Terminal dissemination of rabies virus in selected rat tissues.
AB  - Fifty rats were divided into 3 groups and challenged via the foot pad route with
      a fixed and 2 different strains of street rabies virus in order to study the
      dissemination of the virus and the affinity for certain tissues of the rat. The
      incubation period for rats inoculated with fixed rabies is shorter than with
      street virus, being 5 to 7 days compared with 10 to 12 days. Rats inoculated with
      the fixed strain were less aggressive and irritable than rats inoculated with
      street virus. The fixed strain demonstrated a greater affinity for the tissues
      studied as compared to the street strains of virus. Both the fixed and street
      strains revealed a low affinity for the parotid gland since no virus could be
      demonstrated in 14 of 20 in the fixed virus group and 27 of 30 in the street
      virus group.

PMID- 15846894
TI  - A case of feline papilliferous mammary adenocarcinoma with widespread metastases.
AB  - A papilliferous mammary adenocarcinoma with generalized metastasis, including
      multiple involvement of the brain, was found in a 14-year old female native born
      cat. No nervous signs except some behaviorial changes were noted.

PMID- 15846895
TI  - Antibody development in pigs inoculated with live or killed cultures of Brucella
      abortus.
AB  - As shown by density gradient ultracentrifugation and column chromatography, pigs
      formed IgM antibodies during the first week following vaccination with Brucella
      abortus, strain 19. At this time their sera reacted in both plate and tube
      agglutination but not in complement-fixation tests. A few days later, when IgG
      antibodies had developed, agglutination titers were still high and some activity
      was recorded in hemolytic complement-fixation tests. A similar sequence was
      observed in pigs repeatedly inoculated with phenol-killed suspensions of B.
      abortus. As the proportion of IgM to IgG antibodies decreased, agglutinin titers
      fell in relation to complement-fixing titers. In some animals the conglutinating
      complement absorption test became positive earlier than the plate agglutination.

PMID- 15846896
TI  - Some effects of experimental Vibrio fetus (venerealis) infection on cattle
      inoculated with a commercial bacterin.
AB  - Four groups of ten heifers were used to study the effect of a commercial Vibrio
      fetus bacterin on the development of vaginal mucus agglutination (VMA) reactions
      and subsequent reproductive performance in the presence of active V. fetus
      infection. Two groups were vaccinated and one of these was infected one month
      later. The other two groups were not vaccinated and one of these was infected. It
      was found that in the absence of infection the bacterin did not produce
      diagnostically significant VMA reactions but in the presence of infection
      reactions comparable with the control group were detected. The infected control
      group required 4.9 services per conception, the first service-conception interval
      was 126.9 days and 50 per cent of the animals aborted. The corresponding figures
      in the infected vaccinates were 3.5 services, 68.9 days and 12.5 per cent
      abortions. It was concluded that although this bacterin has a beneficial effect
      on reproductive performance in the presence of genital vibrosis, maximum breeding
      efficiency will not be obtained unless V. fetus infection is eliminated.
      Persistent local reactions appeared at the site of inoculation in the majority of
      the vaccinated animals.

PMID- 15846897
TI  - Experimental exposure of pigs to infectious bovine rhinotracheitis (IBR) virus.
AB  - Thirteen specific-pathogen-free pigs were used in an experiment to determine the
      pathogenicity of IBR virus for pigs. Three pigs were used as controls, eight were
      exposed to IBR virus by either the intravenous, subcutaneous, intratracheal, or
      intranasal route, and two pigs served as contact controls. The clinical response
      consisted of a temperature rise, depression and variable lymphocytosis. The major
      tissue alterations were interstitial pneumonitis, and peribronchiolitis with
      round cell aggregates and giant cell formation. IBR virus was not recovered from
      any of the pigs. A serologic response was detected in only the pig injected
      intravenously.

PMID- 15846898
TI  - Some missing measurements in comparative medicine.
AB  - At the present time it is difficult to make comparisons of animal diseases in
      various geographic areas. Some missing measurements which limit these comparisons
      are: the lack of an internationally accepted system to classify diseases; the
      lack of routinely collected information about animal births, diseases, and
      deaths; the lack of normal or standard values for many species; and the lack of
      methods to define animal populations at various points in time. Most of these
      problems have been faced and solved for human diseases. Work should be started
      immediately to develop similar research methods for animal diseases.

PMID- 15846899
TI  - The purification and concentration of hog cholera virus.
AB  - Partial purification of hog cholera virus (HCV) using a simple batch-type
      chromatographic procedure with magnetic ferric oxide (MFO) is described.
      Infectious HCV was adsorbed from isotonic solutions to MFO and was eluted under
      conditions of low ionic strength and high pH. Aqueous solutions of 0.01 M sodium
      cyanide or 0.0003 M ammonium hydroxide effectively dissociated MFO-HCV complexes.
      The data indicate that 50 to 100% of the original HCV infectivity was recovered
      concomitant with a 90 to 95% reduction of extraneous organic nitrogen.MFO
      purified HCV was concentrated by density gradient type centrifugations in
      buffered solutions of cesium chloride and sucrose. Prolonged isodensity
      centrifugations of concentrated MFO-purified HCV indicated a buoyant density of
      1.14 to 1.15 gm/ml for the strain of virus used.

PMID- 15846900
TI  - Experimental enteric colibacillosis in piglets.
AB  - Eleven of 20 piglets inoculated orally with Escherichia coli:0101:KU460(A):NM and
      one of 18 piglets inoculated orally with E. coli:08:K87, K88a, b:H19 developed
      enteric colibacillosis. Successful reproduction of the disease was associated
      with recovery of a dense growth in a nearly pure culture of the inoculated strain
      from the feces. Piglets which remained clinically normal had none, or very few,
      of the inoculated strain in their feces. Seventeen control piglets inoculated
      orally with the non-enteropathogenic E. coli:043:K -:H28 remained normal.

PMID- 15846901
TI  - Characterization of Pasteurella hemolytica isolated from the respiratory tract of
      cattle.
AB  - Morphological, cultural, biochemical, and serological characteristics of 43
      strains of Pasteurella hemolytica isolated from the respiratory tract of cattle,
      including 37 that had shipping fever, were determined. With one exception, all
      strains satisfied the major criteria for differentiation of the species from P.
      multocida - hemolysis on blood agar, absence of indole production, and growth on
      MacConkey's agar. Many strain variations in fermentative capacity were noted,
      although other biochemical characteristics were relatively constant. The ability
      of a strain to ferment carbohydrates often depended upon the medium in which the
      test was conducted. All strains studied were identified as type A strains on the
      basis of colonial morphology, biochemical, and growth characteristics, and
      sensitivity to penicillin. When grouped on the basis of serological reactions, 38
      strains were type 1, three were type 2, one was type 11, and one was untypable;
      34 of the shipping fever strains were 1 and three were type 2.

PMID- 15846902
TI  - A plaque assay for duck plague virus.
AB  - A plaque assay for duck plague virus was developed for a chicken embryo-adapted
      virus and a duck lethal virus and used to determine the identity of these
      viruses. Using the plaque inhibition neutralization test, duck plague virus was
      differentiated from Newcastle disease, fowl plague, and duck hepatitis viruses.
      The plaque morphology is described.

PMID- 15846903
TI  - [Diagnosis of Helicobacter pylori by polymerase chain reaction].
AB  - The Polymerase Chain Reaction (PCR) is a biotechnological useful tool for the
      diagnosis of bacteria or viruses with high in vitro growth requirements.
      Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the
      upper part of the gastrointestinal tract and its diagnosis is very important
      since it is associated with chronic gastritis, peptic ulcer, and gastric
      carcinomas. Because of the difficult growth requirements of the H. pylori, the
      PCR is being used for its diagnosis in samples of gastric biopsy, gastric juices,
      feces, saliva and subgingival plaque using specific H. pylori DNA fragments. This
      paper is a literature review that outlines the use of PCR in the diagnosis of H.
      pylori, the benefits and future applications of this technique in this area.

PMID- 15846904
TI  - HIV/AIDS in the small cities: a Brazilian epidemiology study.
AB  - Analyzing social, behavior and morbidity data of serum-positive individuals to
      the test anti-HIV in a Brazilian town city, they were detected: diffusion of the
      virus of the human immunedeficiency by via heterosexual, in epidemic profile
      similar to the HIV/AIDS appearance time in the world economically underdeveloped;
      change of sexual behavior from people when they notice they were involved with
      HIV; importance of the access to the attendance in the reduction of the morbidity
      of infected people with HIV and for the transmissibility of this disease in the
      community. The affected population was between 20 and 49 years and lower
      socioeconomic level, where the illicit use of drugs was not a risk event, the use
      of alcoholic drink was an important prominence. The morbidity owed HIV was from
      low seriousness to moderate one and the answer to the treatment was excellent,
      with just few collateral effects. Pregnant women had access to the treatment when
      they were still in good health conditions, but with levels of significant viral
      load for the vertical HIV transmission.

PMID- 15846905
TI  - [Different circulation patterns of subgroups A and B of human respiratory
      syncytial virus in some provinces of Cuba].
AB  - The nucleotide sequencing of the protein G C-terminal region of 37 samples taken
      from nasopharyngeal washings of under one-year old children from some Cuban
      provinces was made for 5 epidemic periods (1995-2000) to find out the circulation
      patterns of strains of human respiratory syncytial virus that is classified in
      two antigenic subgroups known as A and B; each of them contains multiple
      variants. Subgroup A has circulated during all these years but subgroup B was
      detected only in the year 2000. The presence of strains with two different sizes
      of protein G (297 aa and 298 aa) was observed whereas subgroup B showed only one
      size (295 aa). Phylogenetic analysis allowed identifying 5 and 2 genotypes within
      subgroups A and B respectively. Viruses present in Cuba were phylogenetically
      related to the strains of other parts of the world. Subgroup A comprised two
      strains very similar to Long prototype strain. Almost all the strains of both
      subgroups in the year 2000 phylogenetically related with strains that circulated
      in South Africa during the same period.

PMID- 15846906
TI  - [Immunization with Leishmania amazonensis subgenomic libraries protects BALB/c
      mice against the challenge].
AB  - A genomic library of Leishmania amazonensis in expression vector of eukaryote
      cells (pEF1HisA, pEF1HisB, pEF1HisC) was prepared. Also two subgenomic libraries
      having each 500 clones approximately were created and BALB/c mice were immunized
      with 50 mg/0,1 mL of DNA from each. Two immunizations were administered
      intramuscularly at 15-day interval. Groups of control mice were immunized with
      DNA from empty plasmid pEF1His, with soluble parasite antigen (100 mg/0,1 mL) and
      saline solution. The size of lesions was measured for 12 weeks and at the end of
      the experiment, the parasite load at lesion sites was determined by plaque
      microtitration method. In mice immunized with subgenomic library DNAI and with
      soluble antigens,the size of lesions was controlled, which reached an statistical
      difference (p< 0,05) in relation to the rest of groups whose lesions increased.
      The parasite load found in lesion sites confirmed the previous results; the
      number of promastigots was significantly lower in those mice already protected.
      It was concluded that in subgenomic library DNA1 there should be genes or gene
      fragments whose in vivo expression induces protective immune response against the
      challenge in the murine model used.

PMID- 15846907
TI  - [Determination of glutathione-S-transferase activity in Culex quinquefaciatus
      strains in Cuba and other Latin American countries].
AB  - In the present paper, we standardized a microtitration assay for the
      determination of specific activity of glutathione-S-transferase using a Culex
      quinquefasciatus strain selected in lab with pyrethroid insecticide
      lambdacyhalothrin for 6 generations (SP6). The saturation values for reduced
      glutathione and 1-chlorine 2,4-dinitrobenzene were 15 mM and 40 mM, respectively;
      we also estimated that 3 minutes was the optimal time in order to differentiate
      resistant strain SP6 from the susceptible reference strain S-Lab (p>0.05).
      Additionally, the optimized microtitration method allowed testing 4 Culex strains
      from Cuba (SANTIAGO DE CUBA, SD4, QUIBU AND SP6), one from Venezuela (MIRANDA),
      one from Colombia (MEDELLIN) and the other from Brazil (RIO DE JANEIRO) for
      glutathione-S-transferase activity. MIRANDA showed the highest activity for this
      detoxifying enzyme. However, the mechanism of detoxyfication in all the strains
      was very unfrequent, which indicates that its role in resistance to insecticide
      for all the studied strains is not so important. Glutathione-S-transferase values
      were compared with non-specific esterase and altered acetylcholinesterase
      frequencies for each of the studied strains.

PMID- 15846908
TI  - [Silent circulation of poliovirus demonstrated by interference against non-polio
      enterovirus].
AB  - Fecal samples were weekly obtained from children under 3 years of age to isolate
      non-polio poliovirus and enterovirus and to expand the knowledge on circulation
      of vaccine-derived viruses during mass campaigns. The steady vaccination
      schedules allow the circulation of these viruses for long periods of time. The
      interference of non-polio enterovirus by vaccine poliovirus was demonstrated in
      children. However, the low percentages of non-polio enterovirus did not show
      significant differences whereas these differences were significant in high
      percentages of vaccine poliovirus isolated in children under one year-old in
      comparison with those of 1 and 2 years of age. Based on this contradiction,
      mathematical calculations estimated the silent circulation of poliovirus that in
      turn made it possible to draw simulated curves. The results were later confirmed
      in another research work by using immunological methods.

PMID- 15846909
TI  - [Some characteristics and opinions of graduates from the master's course on
      epidemiology. Havana 1984--1999].
AB  - Data from the Teaching Department records on, age, gender origin and basic
      profession of foreign and Cuban students were analyzed, including the opinions of
      a sample of the Cuban graduates up to 1999, who were administered a survey
      designed to evaluate the impact of the course. "Pedro Kouri" Tropical medicine
      Institute is giving the Master's course on Epidemiology since 1984. Out of the
      254 graduates up to 1999, 97 were foreigners (75 from Spain); 54.8% of the Cubans
      came from Havana City and Havana provinces. The mean age was 31 years for
      foreigners and 36.9 years for Cubans. Most of the students expressed their great
      satisfaction with the surveillance and research knowledge and skills acquired,
      stating that they had met their expectations in a good quality course, but others
      pointed out that they were not satisfied with the time allocated to Quantitative
      Techniques for Epidemiological Research, Statistics and Computer science modules.
      It was concluded that the differences in origins and age of the Cuban students
      makes it necessary to reformulate academic formation policies and strategies so
      as to increase the educational efficiency according to individual needs. No
      gender differences were found in the Cuban group where physicians prevailed.
      Generally speaking, opinions about the course were very positive.

PMID- 15846910
TI  - [Mycrob-1000: an alternative for the rapid determination of urine culture in the
      primary health level].
AB  - The use of equipment Mycrob-1000 in detecting urinary infections in 4 hours in a
      primary health care center is evaluated. Two hundred fifty eight urine samples
      obtained from spontaneous miction were processed; the reference method was
      counting of colony-forming units per urine millimeter inoculated in Petri plaque
      in CLED medium. The coincidence rate between both methods was 92,31, with
      sensitivity and specificity rates of 79,00% and 96,95% respectively. The level of
      sensitivity was affected by factors not directly dependent on the equipment. High
      values of specificity and of coincidence achieved by this equipment in relation
      to the reference method facilitates its use in urine culture, making possible to
      differentiate negative urine samples in 4 or 5 hours and to focus work and
      resources on positive samples.

PMID- 15846911
TI  - [Antimicrobial susceptibility in non-typable Haemophilus influenzae strains
      isolated from healthy children].
AB  - Antimicrobial susceptibility of 79 non-typable Haemophilus influenzae isolations
      obtained from healthy children that attended two day-care centers in Marianao
      municipality. It was found resistance to trimetoprim/sulfamethoxazole (41,77 %),
      tetracycline (18,99), ampicilline (17,72 %), amoxicillin/ clavulanic acid (7,59
      %) and chloramphenicol (6,33 %). 25,81 % of isolates showed multiresistance. 100
      % of studied cases was sensitive to ceftriaxone, cefuroxime and norfloxacin.
      28,57 % of ampicilline-resistent isolates produced beta-lactamase enzyme.
      Chloramphenicol resistance was mediated by the production of chloramphenicol
      acetyltransferase enzyme.

PMID- 15846912
TI  - [Obtention of specific antisera for the serotyping of Cryptococcus neoformans
      var. neoformans].
AB  - The obtention of antisera at the Mycology Laboratory of "Pedro Kouri" Institute
      of Tropical Medicine was proposed to allow the rapid identification of the
      varieties and serotypes of Cryptococcus neoformans, since it is very important
      from the clinico-epidemiological point of view to know them. By immunizing
      rabbits with formalized whole cells of the 4 serotypes of this yeast, it was
      possible to obtain antisera that were absorbed with cells of the heterologous
      serotypes. 3 antisera capable of differentiating the neoformans var. (anti AD)
      and its respective serotypes (anti-A and anti-D) were attained. This paper will
      contribute to the knowledge of the epidemiology of this important disease in the
      Cuban setting for being the first time that useful antisera are obtained in Cuba
      to identify the serotypes corrresponding to the neoformans variety, which is the
      main causal agent of criptococcosis.

PMID- 15846913
TI  - [Use of the restriction analysis in the quality control of the strain of Cuban
      biolarvicide BACTIVEC].
AB  - The genomic characterization of the strain used in manufacturing biolarvicide
      BACTIVET was shown in this paper. Digestion patterns of Bacillus thuringiensis
      reference strain 266 from the collection of Pushkin Institute located in former
      Leningrad and of two strains isolated from 2 batches of biolarvicide were
      compared. Chromosomal DNA digestion was performed by enzymes Hindlll and EcoRI.
      The same restriction pattern was observed in all cases, which is indicative of
      genetic stability of the active ingredient of biolarvicide BACTIVET.

PMID- 15846914
TI  - [Serological response by ELISA and MAT in Cuban volunteers vaccinated with vax
      SPIRAL].
AB  - The seroconversion of 408 vaccinated individuals and 135 placebo included in 2
      clinical trials of the Cuban vaccine against human leptospirosis was studied. 2
      vaccine doses and 5 schemes were studied. Of 38 vaccinated subjects (Phase I), 11
      (29 %) seroconverted by MAT and 12 (32 %) by ELISA, whereas in 33 placebo,
      seroconversion was observed in 2 (6 %) and 3 (9 %), respectively. In Phase II, of
      68 vaccinated individuals (doses of 0.25 mL) and of 65 (doses of 0.50 mL),
      seroconversion was attained in 21 (31 %) and 16 (25 %) by ELISA, respectively, 9
      by MAT (13 %) and 7 (11 %) were positive. There were no significant differences
      between the doses used. The seroconversion by MAT in 237 subjects vaccinated with
      different schemes was 22.4 %. No marked differences were observed between them.
      In most of the reactive individuals, antibody levels were found in at least one
      of the vaccine strains. It was recommended to search and evaluate other methods
      to show in vivo the level of protection of this vaccine.

PMID- 15846915
TI  - [Ingestion of Culex quinquefasciatus larvae (Diptera: Culicidae) by Girardinus
      metallicus (Cyprinodontiformes: Poecilidae)].
AB  - Data on ingestion of Culex quinquefasciatus Say 1823 larvae by Girardinus
      metallicus, Poey 1854 under lab and field conditions were obtained and compared
      to those reported on the same species by other authors. It was observed that G.
      metallicus is not so aggressive as other species of larvivorus fish in capturing
      larvae. The consumption of larvae is higher in females since males prefer feeding
      on vegetation. Because of the bioecological characteristics of the species,
      resistance to management and survival in cultural conditions, G. metallicus is
      recommended to be used as bioregulator of mosquito larvae.

PMID- 15846916
TI  - [P-24 antigenemia: correlation with some clinical and epidemiological aspects in
      100 HIV-infected Cuban subjects].
AB  - A non-probabilistic selection of 100 Cuban patients at different stages of HIV
      infection, according to the revised classification of the Centers for Disease
      Control and Prevention of 1987, was made from a set of 130 persons with
      serologically-confirmed HIV infection. Clinical and epidemiological information
      about each case was collected and peripheral blood samples were taken to detect
      HIV-1 p24 antigen. The frequency of p24 antigenemia detection and concentration
      were correlated with available clinical and epidemiological data. P24 antigenemia
      was significantly more frequent in AIDS patients. No difference was found between
      the type of opportunistic diseases diagnosed in the group of patients with
      detectable p24 antigen and the group that was negative to antigen presence;
      although in the group with antigenemia concentrations over 100 pg/ml, more than
      one AIDS-related disease was often diagnosed simultaneously. A history of sexual
      intercourses with several persons who had been infected with HIV was much more
      frequent in patients with antigenemia, and it was associated with a shorter time
      elapsed from the probable date of infection to the date of their classification
      as AIDS patients. These results were compared with the literature review
      information.

PMID- 15846917
TI  - [Isolation of aspartic proteinases at different stages of development of
      Boophilus microplus tick].
AB  - The magnitud of tisular expression of aspartic proteinases at juvenile stages was
      analyzed in adult young Boophilus microplus ticks as well as the effect of one of
      the most widely used aspartic proteinase inhibitors (pepstatin A) on their
      development. The isolation and quantification of acid proteolytic activity was
      performed in samples of parasites with different stages of the digestive process
      where aspartic-proteinase activity was confirmed and a tendency to increased
      values of enzymatic activity per miligram of total weight was observed during the
      development of adults female ticks, with a lowering of this ratio just when they
      are full up. Adding pepstatin A to the ingesta at 14 and 70 mmol concentrations
      had no effect on the viability of young female ticks while they were kept in
      vitro for 24 h, so this rules out the immediate toxic effects of this compound.
      However, in those experiments where adult female ticks after receiving the
      various ingestas, are put together with sexually competent male ticks in
      isolators for 6-7 days, the viability showed different results (p< 0,01) at a 70
      mmol concentration. The effect on the development of young adult female ticks was
      slight, but it indicates hat there might be a selective inhibitory action of
      pepstatin A on aspartic-dependent enzymes.

PMID- 15846918
TI  - [Building of a genomic library of Leishmania amazonensis and its expression in
      BALB/c mice's muscle].
AB  - A genomic library of Leishaminia amazonensis was built through a pcDNA3 vector,
      with expression promoter in eukaryot cells, to contribute to the application of
      immunization technology with nucleic acids in leishmaniasis. To show the
      expression genomic library in the muscles of mice immunized with it, the indirect
      immunofluoresce technique was used. A mix of sera with high antileishmania titers
      from an area where L.braziliensis infection is predominant was used as primary
      antibody. A library of 80% recombinant clones was obtained. Antigen determinant
      expression was confirmed in immunized BALB/c mice's muscles, according to the
      results of immunofluorescence testing.

PMID- 15846919
TI  - [Inhibition of invasion and multiplication of Toxoplasma gondii in human colonic
      epithelial cells by a monoclonal antibody against protein SAG2].
AB  - By an bromodeoxyuridine (BrdU) incorporation assay, it was proved hat an IgG 1
      subclass, murine monoclonal antibody to surface protein SAG2 of Toxoplasma gondii
      is capable of reducing the invasion and multiplication of the parasites in highly
      differentiated mucine secretory HT29-18N2 line cells from a human colon
      adenocarcinoma. This result shows the importance of surface protein SAG2 of
      T.gondii in invasion and further multiplication of parasites in the host cell.

PMID- 15846920
TI  - [Evaluation of the humoral immune response by Western Blot test in mice immunized
      with expression genomic library of Trypanosoma cruzi].
AB  - An expression genomic library of Trypanosoma cruzi was built by using plasmid pc
      DNA3 as a vector. This library served to immunize by intramuscular administration
      BALB/c inbred mice. A positive control group to which T. cruzi soluble antigens
      were administered and other group which was given the same plasmid used for the
      building of the genomic library were included in this study; another group was
      not immunized. Blood was extracted from the retrorbital plexus of all the mice
      two weeks after the third vaccination so as to study the specific antibody
      response to soluble parasite anigens through the Western Blot technique. The
      antibody response was shown in animals immunized with the expression genomic
      library and with soluble parasite antigens.

PMID- 15846921
TI  - [Application of an alternative method to counting in Neubauer chamber to
      determine Trichomonas vaginalis concentrations].
AB  - It was demonstrated that there is a relation of cell concentration with the
      parasite reading in an ELISA reader. It was determined that absorbance showed
      significant values in wavelengths of visible range and the possible minimum
      wavelength (450 nm)was chosen to guarantee the maximum sensitivity. Likewise, it
      was confirmed that absorbance significantly increased (p < 0.001) after the plate
      was filled up, it stabilized in the 40m-2h time interval when applying 100, 150,
      200 or 300 ml per well of the various cell concentrations, it was proved that the
      optimum volume was 150 ml, a r2 = 0,9986 was reached, and the coefficient of
      correction(p < 0,001) and the gradient(p < 0,001)were highly significant. In the
      5 x 10(4) to 1.5 x 10(7) cell/mL interval, there was an average variation
      coefficient of 1.75% (0.25-3.17%). Under these conditions, the quantification
      limit was 5,14 x 10(4) cell/mL. Finally, it was shown that the correlation of
      counting in Neubauer chamber and optical density was significant.

PMID- 15846922
TI  - [Intestinal parasitic infections in 4 child day-care centers located in San
      Miguel del Padron municipality, Havana City, 1998].
AB  - A coproparasitologic study was performed on 456 children aged 1-5 years from 4
      day-care centers located in San Miguel del Padron municipality during November
      1998, with the aim of finding out the behaviour of the main intestinal parasites
      and particularly how Giardia lamblia was affecting this child population. Three
      fecal specimens were collected from each child in every other day, which were
      processed by coproparasitologic methods such as direct testing and Ritchie's
      concentration technique. The most frequently identified parasite was G. lamblia
      with 249 positive cases for a prevalence rate of 54.6%. The second one was
      Blastocystis hominis (29.6%) followed by Endolimax nana(23.9%). Coccidia like
      Crystosporidium parvum and Cyclospora cayetanensis exhibited low frequencies, 0.6
      and 1.5% respectively, being the majority of the cases located in only one day
      care center. These results confirmed that G. lamblia is the most prevailing
      parasite in day care centers, with peak frequency values in 2-4y age group and no
      differences between sexes.

PMID- 15846923
TI  - [In vitro nystatin sensitivity of vaginal isolates of Candida spp].
AB  - The minimum inhibitory concentration (MIC) of nistatine, one of the most used
      antifungal agents for this micosis, was determined in 68 Candida strains isolated
      from vaginal smears. Candida albicans represented 75% of the total strains
      whereas C. parapsilosis, C. krusei and C. glabrata were much less frequently
      found. The predisposing factors were pregnancy and antibacterial treatment
      whereas leukorrhea and itching were the prevailing symptoms in most of the cases.
      MIC values from the use of a broth dilution method ranged from 0,5-8mg/mL and the
      geometric mean was 1.36mg/ mL. For C. albicans, MIC was 4mg/mL due to two strains
      that showed the highest MIC values (8 mg/mL). Similarly, the strains showed low
      MIC values, this means that therapeutic failures are not inherent to the
      emergence of resistant strains.

PMID- 15846924
TI  - [Helicobacter pylori infection in a group of HIV/AIDS patients].
AB  - The prevalence of H. pylori infection in AIDS patients has been controversial. A.
      controlled prospective and descriptive study was conducted in a group of 64 HIV
      infested patients. H. pylori detection was carried out by endoscopic study during
      which two biopsy samples of gastric antrum and body were taken for the histologic
      study and other 2 samples of gastric antrum and body for urease testing. H.pylori
      infection prevalence was 56.3%. The comparison group was composed by 110
      serologically HIV-negative patients, with an infection prevalence rate of 77.2%.
      In the HIV-AIDS group, the frequency of gastric ulcer was 1,5% and no duodenal
      ulcer was found whereas the comparison group showed a frequency of gastric and
      duodenal ulcers of 1.8 and 15.5% respectively. HIV+/AIDS patients in category I
      exhibited an H. pylori infection prevalence of 68.7%, category II, 39.2% and
      category III, 21,0%. A reversed association was observed between the level of
      immune deterioration and the prevalence of H. pylori infection.

PMID- 15846925
TI  - [Bacterial meningitis: geographic and referential study in the City of Havana in
      1998].
AB  - The behaviour of bacterial meningitis with identified agent in the City of Havana
      in 1998. The implementation of Geographic Information System Mapinfo 4.1 made it
      possible to know the spatial distribution of the sick people. As a result, we
      found an area of circulation of Neisseria meningitidis located to the northeast
      center; an area of prevalence of Streptococcus pneumoniae to the north and
      northeast of the city and zones located to the center, east and south where
      Haemophlus influenzae prevailed. These areas were related to the main sources of
      environmental pollution in the province. THe importance of the spatial analysis
      for expanding the knowledge for an epidemiological study was evidenced.

PMID- 15846926
TI  - [Vegetative pyoderma gangrenosum associated with renal failure].
AB  - A case report was presented in which a patient developed vegetative pyoderma
      gangrenosum that was concomitant with acute renal failure; this led to the
      critical condition of the patient. He was initially treated with systemic
      antibiotics because his clinical picture was considered to be pyodermitis, but
      the response was unsatisfactory. After being treated with levamizol and alfa
      interferon, an improvement in his general condition and skin lesions was
      observed. Then surgical exeresis was successfully performed, with skin self
      grafting in the face and penis lesions. Pyoderma gangrenosum lesions relapsed but
      they were treated with prednisone, and then there was a rapid elimination of
      lesions every time they came up.

PMID- 15846927
TI  - [Echinococcus granulosus infection (hydatid cyst): a case report].
AB  - Larval Echinococcus granulosus infection (hydatid cyst) was reported in a 10
      years-old Ukranian girl. The clinical manifestations were slight since she only
      complained of frequent abdominal pain. The diagnosis was made by ultrasound and
      immunoenzymatic detection of antibodies to Echinococcus (ELISA). Antibody titers
      were 1/800. She was repeatedly treated with albendazol, and she managed to
      recover while the size of her cyst was reduced.

PMID- 15846928
TI  - [Candida albicans serotype B in HIV-positive patients].

PMID- 15846929
TI  - [Criptoccocosis: necessary warning].

PMID- 15846931
TI  - [International Cientific Meeting "Leptospirosis 2001", May 17-18, 2001].

PMID- 15846930
TI  - [Common basis of the fundamental subjects of master's programs at Pedro Kouri
      Tropical Medicine Institute].

PMID- 15846932
TI  - Epidemiology of leptospirosis.

PMID- 15846933
TI  - [Adaptation of Leptospira interrograns (sensu stricto) to fresh water].
AB  - The contact with polluted waters is one of the main risk factors to catch
      leptospirosis. A study is presented about the adaptation of Leptospira
      interrograns to nutrient-lacking water media. For this end, leptospires were
      incubated in distilled water and tampon saline solution for an undetermined
      period of time. Leptospires kept viable in water for 98 days whereas the
      incubated ones in tampon saline solution survived 3 weeks only. Protein cellular
      and external membrane components were analyzed with electrophoresis in acrylamide
      gel (SDS-PAGE). When OM protein profiles of leptospires kept in water were
      compared to those OM profiles of cells cultured in ENJA medium, some differences
      were observed. A 56 kDa protein was present in leptospires kept in water for a
      week. This protein was identified as GroEL through Western Blot test.

PMID- 15846934
TI  - [Clinical and epidemiological behavior of human leptospirosis in Los Palacios
      municipality, Pinar del Rio, Cuba].
AB  - A descriptive-retrospective study was performed to find out some epidemiological
      aspects of leptospirosis in Los Palacios municipality in the period January 1996
      to December 1998. Data were obtained from an epidemiological survey of
      leptospirosis cases, which was made y the Municipal Hygiene and Epidemiological
      Center. The results were 94% of cases were males; the most affected aged group
      was 14-19y (21,8%). Fever (100%), myalgia(84%) and arthralgia (62%) were the most
      common clinical findings. Rice harvesting work (87,5%) was significantly
      associated to the onset of disease.

PMID- 15846935
TI  - [Rats and dogs: important vectors of leptospirosis in agricultural areas in
      Cuidad Guzman, Jalisco].
AB  - A study was conducted to determine how important rats and dogs are in the
      dissemination of leptospirosis in farms and stales located in Ciudad Guzman,
      Jalisco. Thirteen of Leptospira interrograns serovarieties were used in
      microagglutination test of serogroups (MAT). Three hundred and fifty four rats
      (Rattus rattus and Rattus norvergicus) trapped in agricultural areas of the place
      were studied; 22 were positive (6,2%) and 34 suspected of leptospirosis (9,6%).
      Also four hundred and nineteen dogs from the region were tested; 22,6 % (95 dogs)
      were positive and 5,7%(24) suspected of L. Interrogans. These results showed that
      both species are important in the dissemination of the disease.

PMID- 15846936
TI  - [Serological study of bovine leptospirosis in Mexico].
AB  - The results of 4 043 bovine sera samples from various Mexican regions, which were
      sent to a diagnosis lab, were analyzed. The method was the agglutination
      technique, taking the dilution rate 1:1000 or higher as positive. The analysis
      revealed 31,1% of seroprevalence and the most frequent serovarietes were hardjo
      (strain H 89 isolated in Mexico), wolffi and tarassovi. There is coincidence with
      early data obtained in Mexico on a 34% of prevalence found in a similar study
      performed in 1994, and with the scientific literature from other countries. The
      former study also indicated that tarassovi and wolffi were the most common
      leptospira, so there is coincidence with the figures in the reviewed literature.
      It was concluded that there was no significant variation in the prevalence rate
      between the 1994 study and the present one; therefore, it is recommended that
      this study be promoted so as to increase the bovine vaccination and achieve a
      reduction in leptospirosis in Mexico.

PMID- 15846937
TI  - [Diagnostic serology of swine leptospirosis in Mexico 1995-2000].
AB  - Results obtained from sample testing of 1970 swines from a number of Mexican
      farms were analyzed. Such samples had been received in the Leptospira Lab of
      Universidad Autonoma Metropolitana de Xochimilco from 1995 to 2000. Sera with
      titers equal to or higher than 1:1000 were considered positive; 39,8% of the
      animals were seropositive (784) and the most frequent serovarieties were
      bratislava, 22.5%; icterohaemorrhagiae strain Palo Alto, 14,5%; portland vere
      strain Sinaloa ACR, 13,8%; icterohaemorrhagiae, 11,1%; grippotyphosa, 8,9%;
      hardjo strain H89,7.2%; tarassovi,7.1%; panama, 5.8%, pomona and hardjo, 5.1%;
      wolffi, 3%; shermani, 2.4%; pyrogenes, 1.2%; canicola, 0.8%; hebdomadis, 0,5%.
      The bratislava serovariety has been reported as the cause of reproductive failure
      in several countries and it holds the first place in serological studies.
      Therefore, the present paper provides information for stating that this is one of
      the most significant serovarieties in Mexico.

PMID- 15846938
TI  - [Growth, virulence and antigenecity of Leptospira interrogans serovar mozdok in
      modified EMJH medium].
AB  - The effect of higher Tween 80 concentrations in EMJH synthetic medium on the
      growth, virulence and antigenecity of Leptospira interrogans serovar mozdok was
      evaluated for increasing the performances and making a full use of the
      detoxifying capacity of bovine serum albumin. The growth was
      spectrophotographically evaluated by the analysis of the bacterial growth
      kinetics; the obtained biomass performance and the consumption of the carbon
      source. The virulence was estimated in Syrian Hamster model whereas antigenecity
      was determined through the microagglutination technique in rabbit's polyclonal
      antiserum. Under controlled culture conditions, the increase of Tween 80
      concentration up to 3.25 mg/ml brought about an acceleration in bacterial
      metabolism that managed to double cell performances with a full consumption of
      the carbon source, without affecting virulence and antigenecity for a number of
      successive subcultures.

PMID- 15846939
TI  - [Reactogenecity and immunogenecity of Cuban trivalent inactivated vaccine against
      human leptospirosis in different vaccination schedules].
AB  - A controlled, randomized assay was performed to evaluate the reactogenecity and
      immunogenecity of Cuban trivalent vaccine against human leptospirosis (vax
      SPIRAL) in healthy volunteers, using different vaccination schemes. A Russian
      made vaccine was used as control. Adverse effects were local symptoms and signs
      (pain, rush, local infiltration, itching, necrosis and abscess) and general
      symptoms and signs(fever, low-grade fever, headache, lipotimia, nausea, vomiting,
      rash and general malaise). The results showed that the vaccine is innocuous since
      no serious adverse effects were observed. Low-grade fever and slight local pain
      were the symptoms and signs that occurred at acceptable levels. Fever was present
      in a small number of volunteers. Similar adverse reactions were reported in the
      groups immunized with Cuban vaccine under different vaccination schemes and in
      those immunized with the Russian-made vaccine. Most of the symptoms and signs
      disappeared after 72 hours. Seroconversion was similar to other bacterines
      against leptospirosis. The achieved results allowed concluding that the Cuban
      vaccine is safe and low reactogenic for human adults.

PMID- 15846940
TI  - [Lepto-dipstick: results of its application to the fast diagnosis of human
      leptospirosis].
AB  - Forty one serum specimens from critical patients who were suspected of having
      human leptospirosis were studied by using simultaneously convencional test Lepto
      dipstick and serogroup microagglutination test (MAT) with live antigens.
      Different reactivity levels were reached in 26 tested samples by Lepto-dipstick.
      This assay and MAT coincided in 85,4% of results. It was confirmed that Lepto
      dipstick detects antibodies to various leptospiral serovars and that the degree
      of intensity of the band staining corresponded with the level of detected
      antibodies by MAT. The implementation of Lepto-dipstick in the diagnosis of human
      leptospirosis allows providing a rapid response to the medical staff in charge of
      the studied cases. This proved that Lepto-dipstick is a rapid method that is easy
      to-read and interpret.

PMID- 15846941
TI  - [Identification of Leptospira isolates by serological and genetic methods].
AB  - Serological and genetic methods were used to study 18 leptospiral strains
      isolated from patients with leptospirosis in 3 Cuban provinces. The strains were
      grouped by microscopic agglutination with 8 polyclonal antisera. Nine monoclonal
      antibodies served to determine the strain serovars. Alternatively, DNA was
      extracted from these strains and applied by a polymerase chain reaction system
      described for pathogenic leptospiras. Amplified DNA was digested by restriction
      enzymes Alu I and Hae III. MAT grouped the strains among serogroups Ballum,
      Ponoma, Canicula and Icterohaemorrhagiae. Monoclonal antibodies determined the
      serovars of seven of the studied strains. For all the strains, an amplified
      fragment of 631 pb was obtained by polymerase chain reaction. The analysis of the
      amplified product with restriction enzymes revealed similar patterns of
      restriction in all the strains. The used methods made it possible to identify all
      the strains at different levels. It is also pointed out that the use of
      monoclonal antibodies allowed to typify seven strains up to the serovar level.

PMID- 15846942
TI  - [Dengue and hemorrhagic dengue fever: a forgotten entity?].

PMID- 15846943
TI  - Dengue hemorrhagic fever: two infections and antibody dependent enhancement, a
      brief history and personal memoir.

PMID- 15846944
TI  - [Notes on the laboratory diagnosis of dengue virus].
AB  - Some aspects of interests connected with the virological, serological and
      molecular diagnosis of dengue and its most severe form, dengue hemorrhagic fever,
      which has turned into the most important arthropod-borne viral disease, are
      updated.

PMID- 15846945
TI  - [Strategies for controlling dengue and Aedes aegypti in the Americas].

PMID- 15846946
TI  - [Correct use of insecticides: management of resistance].
AB  - A review of the effective strategies, outlooks and tactics connected with the
      management of resistance was made. It was explained that these tactics are not
      excluding, since some of their elements may be used to set up a long-term
      resistance management program, and that the strategy should be based on a deep
      knowledge of the implications for each candidate insecticide resistance, and of
      the ecology and biology of those species involved. It was also stressed that this
      strategy should comprise all the non-chemical available fighting measures.

PMID- 15846947
TI  - [Economic impact of dengue 2 epidemic in Santiago de Cuba, 1997].

PMID- 15846948
TI  - ["Fever of unknown origin" (FUO) in adults. Main symptoms: fever 38.3 degrees C
      (axillary) > 3 weeks].

PMID- 15846949
TI  - [Interview with Professor Dr. Reinhard Saller, Zurich University Hospital. Willow
      bark extract--more than a natural alternative in antirheumatic therapy?].

PMID- 15846950
TI  - [Patients with inflammatory bowel disease in specialist gastroenterology
      practice: a prospective survey].
AB  - PRINCIPLES: Ulcerative colitis (UC) and Crohn's disease (CD) are chronic
      relapsing disorders with significant implications for health care. The latest
      epidemiological data for Switzerland were prospectively collected in 1971.
      METHODS: A prospective nationwide survey over a period of five weeks was
      initiated by IBDNet.ch and a questionnaire sent to all gastroenterologists in
      hospital or private practice. RESULTS: The response rate was 42% (85/204). 930
      patients were recorded, 505 (54.3%) had CD, 425 (44.9%) UC, male/female ratio was
      47 vs. 53%, mean age 44 +/- 15.8 years (standard deviation, SD). Median duration
      of disease was 84 months (mean 101 +/- 3.15 SEM). In CD, intestinal involvement
      was colitis in 135 (26.7%), ileitis in 142 (28.1%) and ileocolitis in 228 (45.2%)
      patients. In UC, (n = 425) pancolitis was present in 182 (43.5%), left-sided
      colitis in 140 (33.6%) and proctitis in 95 (22.9%) cases. Diarrhea was the main
      symptom (52.8%; CD/UC: 47.5% vs. 59.2%; p < 0.001), as well as abdominal pain
      35.8% (CD/UC: 48.5% vs. 20.1%; p < 0.001), rectal bleeding 27.8% (CD/UC: 8.4% vs.
      51.8%; p < 0.001). Weight loss was reported in 12.2% (CD/UC: 14% vs. 9.8%),
      anemia in 15.1% ( CD/UC: 14.8% vs. 15.3%). The mean number of medications per
      patient was 2.1 (+/- 1.2SD), CD/UC 2.4 vs. 1.9 (p < 0.001). 5-ASA preparations
      per os were used in 74%, topical treatment in 18% in both groups. Corticosteroids
      CD/UC 56.5%/54%, oral or topical budesonide (CD/UC: 19% vs. 16%; CD/UC: 1.9% vs.
      2.1%). Antibiotics (18%) or immunomodulatory therapy, as well as infliximab, was
      similar in both groups. Inflammatory bowel disease related surgery was performed
      in 233 (25.4%): resection of stenosis or in fistula 132 (14.2%), colectomy (total
      and subtotal) in 70 (7.5%), colostomy in situ in 21 patients (2.3%).
      Extraintestinal manifestations occurred in 36.6%, significantly more in patients
      with CD vs. UC: 25% vs. 16% (p < 0.001). Arthritis 18.6% (CD/UC: 22.6 vs. 13.7%,
      p < 0.001) and osteoporosis were recorded in 9.7% (CD/UC: 13.65 vs. 4.8%, p <
      0.001). Skin and eye involvement was seen in 6.3% and 2% respectively (CD/UC: 7.8
      vs. 4.5% and 3.1 vs. 1%, p = n.s.). CONCLUSION: In conclusion, we attempted to
      characterise the patients with IBD seen by specialist gastroenterologists in
      Switzerland. The ultimate goal would be to set up a national cohort study to
      collect long-term data, which could be useful for epidemiological studies in
      patient and health care management, as well as for therapeutic intervention
      studies and basic research.

PMID- 15846951
TI  - [Injury to body and soul--psychiatric consequences of road traffic accidents in
      children and adolescents].
AB  - Road traffic accidents are a major cause for severe injury in children and
      adolescents. Many victims also suffer from psychological consequences, such as
      posttraumatic stress disorder, traffic-related fears or mood disturbances. High
      levels of distress during and immediately after the accident are associated with
      severe posttraumatic stress symptoms. Routine consideration of the psychological
      impact of road traffic accidents should receive the same priority as screening
      for physical injury.

PMID- 15846952
TI  - [Reactive arthritis induced by Clostridium difficile enteritis].
AB  - This article reports the case of an acute monoarthritis of the ankle occurring in
      a HLA-B27 positive female patient who presented with diarrhea and fever. We
      retained the hypothesis of a Clostridium difficile colitis, as she had previously
      received an antibiotic treatment. The culture of the synovial fluid remained
      sterile, which postulated that this arthritis was reactive. The diagnosis was
      confirmed by the presence of toxins A and B in the stool and positive culture.
      The outcome was satisfactory with metronidazole therapy.

PMID- 15846953
TI  - [SAPHO or Sappho? 43-year-old patient, housewife].

PMID- 15846955
TI  - Alive and kicking.

PMID- 15846954
TI  - [Chronic thoracic vertebral syndrome by roundabout diagnosis].
AB  - Back pain, especially in the lumbar region is a frequent symptom in ambulatory
      medicine. The differential diagnosis is wide and ranges from rather harmless
      muscular distortions to systematic disease, such as chronic infections or cancer.
      Our case shows, that sometimes the diagnosis is not quite simple to determine. A
      atypically picture may lead to unnecessary further evaluations and in some case
      even invasive diagnostic tests. However, the benefit should overweight the harm
      and costs. Not every back pain needs to be examined in every case and with every
      diagnostic possibility. Recent guidelines recommend a conservative approach to
      patients with back pain if they are younger than 50 years of age and if cancer or
      chronic infection is not suspected from their clinical evaluation and past
      medical history. For patients older than 50 years of age and suspicion for
      systematic disease, a radiograph of the spine and a routine laboratory
      measurement, including markers of inflammation (e.g. C-reactive protein),
      alkaline phosphatase, PSA (prostate-specific antigen) and immune-electrophoresis
      is mandatory. More detailed diagnostic steps, e.g. CT or MRT, should be performed
      if symptoms persist for longer than 6 weeks. In addition, if symptoms do not
      resolve with analgesia and physiotherapy more invasive therapeutically options
      may be considered.

PMID- 15846956
TI  - Power lines aren't the enemy.

PMID- 15846957
TI  - Consultation, enforcement are separate.

PMID- 15846958
TI  - Coaching your subordinates.

PMID- 15846959
TI  - Locking out the unexpected.

PMID- 15846960
TI  - Writing machine-specific procedures.

PMID- 15846961
TI  - Safeguarding against heat hazards.

PMID- 15846962
TI  - The portable oxy-fuel system debate.

PMID- 15846963
TI  - Heading off disaster.

PMID- 15846964
TI  - Ear plugs: a field guide.

PMID- 15846965
TI  - NFPA 1600 update.

PMID- 15846966
TI  - Good practices for flammable and combustible liquids.

PMID- 15846967
TI  - Preventing falls in bridge construction.

PMID- 15846968
TI  - A DM-style approach to stroke recovery.

PMID- 15846969
TI  - Putting the brakes on inappropriate ER utilization.
AB  - It's a common problem--particularly in Medicaid populations, but it can be dealt
      with creatively. Two health plans share their successful strategies for directing
      frequent users of the ER to more appropriate utilization of primary care.

PMID- 15846970
TI  - Technology-based decision support fuels quality improvement.
AB  - In the first large-scale study of its kind, a claims-driven decision support
      system has shown that it can reduce errors and slash utilization costs by
      notifying physicians of care improvement opportunities. It's an idea that has
      already been embraced by a number of large employers and managed care
      organizations, and more innovations are on the way.

PMID- 15846971
TI  - The acid domain located at the C-terminus of the Su(Hw) protein represses
      transcription in the yeast two-hybrid system.

PMID- 15846972
TI  - The regulatory mechanism of the mitochondrial ATP-dependent potassium channel by
      the adenine nucleotides.

PMID- 15846973
TI  - Pools of 14C-malic acid as a substrate for pyruvate production for the DOXP/MEP
      pathway of biosynthesis of carotenoids in chloroplasts.

PMID- 15846974
TI  - The gene of the complement-binding protein, an important anti-inflammatory factor
      of orthopoxviruses, is deleted from the genome of Western African strains of
      monkeypox virus.

PMID- 15846975
TI  - Quantum chemical analysis of the mechanism of ATP hydrolysis.

PMID- 15846976
TI  - Characteristic features of metabolism of xenobiotics in the system of cytochrome
      P-450 in crow (Corvus cornix) liver.

PMID- 15846978
TI  - Identification of microsatellite mutations in parthenogenetic lizards Darevskia
      armeniaca.

PMID- 15846977
TI  - Analysis of interaction between proteins containing the BTB domain in the yeast
      two-hybrid system.

PMID- 15846979
TI  - Electron-conformational model of nonlinear dynamics of the ryanodine channel
      lattice in cardiomyocytes.

PMID- 15846980
TI  - Electron probe microanalysis of intracellular potassium concentration in early
      mouse embryos.

PMID- 15846981
TI  - Fixation of atmospheric nitrogen in the water by heat or light with the formation
      of nitrogen oxides.

PMID- 15846982
TI  - Satellite DNA of lizards of the genus Lacerta s. str. (the group L. agilis), the
      family Lacertidae.

PMID- 15846983
TI  - Cytokinins activate transcription of chloroplast genes.

PMID- 15846984
TI  - The search for biochemical predictors of the NAT2 phenotype to optimize
      prophylaxis and pharmacotherapy of hepatic cirrhosis.

PMID- 15846985
TI  - Differences in substrate and inhibitor specificity of cholinesterase activity of
      optical ganglia of the squid Ommastrephes bartrami (Les) as a characteristic of
      isolation of populations from different areas of a disjunctive home range.

PMID- 15846986
TI  - A new approach to obtaining high-activity RNase, DNase, cholesterolesterase, and
      trypsin from cattle pancreas.

PMID- 15846987
TI  - Divergence of de novo biosynthesis of inosine-5'-triphosphate.

PMID- 15846988
TI  - Induction of expression of the dehydrin gene TADHN and accumulation of abscisic
      acid in wheat plants in hypothermia.

PMID- 15846989
TI  - Generation of calcium signal in pollen grains triggered by depolarization of the
      plasma membrane.

PMID- 15846990
TI  - The retrotransposon Tv1 forms infectious virus-like particles in some lines of
      Drosophila virilis.

PMID- 15846991
TI  - Mitochondrial regulation of production of reactive oxygen species and nitrogen in
      rat cells of kidney during ischemia/reperfusion.

PMID- 15846992
TI  - The antiviral activity of the combinations of netropsin derivatives with modified
      nucleosides and phosphonoacetic acid as estimated in the model of herpesvirus
      type 1 in a vero cell culture.

PMID- 15846993
TI  - Canonical and noncanonical MDG4 (Gypsy) sequences contained in Drosophila
      melanogaster genome.

PMID- 15846994
TI  - Fluorinated alpha-aminophosphonates--a new type of irreversible inhibitors of
      serine hydrolases.

PMID- 15846995
TI  - Euthanasia--the erosion of trust?

PMID- 15846996
TI  - Sleep, performance and the European Working Time Directive.

PMID- 15846997
TI  - The science of sleep.

PMID- 15846998
TI  - Assessment and management of insomnia.

PMID- 15846999
TI  - Assessment and management of excessive daytime sleepiness.

PMID- 15847000
TI  - Parasomnias.

PMID- 15847001
TI  - Sleep, driving and the workplace.

PMID- 15847002
TI  - Making clinical governance work.
AB  - This paper summarises a conference that took place at the Royal College of
      Physicians about the work of the Clinical Effectiveness and Evaluation Unit
      (CEEu) and the National Collaborating Centre for Chronic Conditions (NCC-CC). The
      importance of the clinical standards, audit, and evidence-based guidelines and
      their contribution to the clinical governance arena was acknowledged. In
      addition, consideration was given to the fact that information provision alone
      does not change clinician behaviour. Multifaceted strategies are discussed and
      lessons learnt examined. The CEEu and NCC-CC have made significant contributions
      at a national level in the development of clinical governance.

PMID- 15847003
TI  - Assisting international medical graduates applying for their first post in the
      UK: what should be done?
AB  - The number of international medical graduates (IMGs) passing the Professional and
      Linguistic Assessment Board (PLAB) examination was six times greater in 2004 than
      in 2000. This has resulted in unprecedented numbers of applicants for junior
      posts, with some attracting over 1,000 overseas graduates. The Royal College of
      Physicians working group on IMGs was established in 2004 to address the problems
      that face newly qualified IMGs. The group has ascertained and now publishes
      current levels of competition for junior posts in order to inform overseas
      graduates of the levels of competition they are likely to encounter. The group is
      seeking ways of selecting applicants when such large numbers apply for posts and
      is looking at ways of improving clinical attachments. The paper considers these
      and other difficulties that IMGs face when they first seek employment in the UK
      and discusses possible solutions.

PMID- 15847004
TI  - International educational partnerships for doctors in training: a collaborative
      framework with the RCP.
AB  - The UK offers excellent postgraduate medical education, and overseas doctors in
      training often covet a period of training in the UK. Some overseas training
      authorities make UK training mandatory prior to appointment as a consultant.
      Unfortunately, the organisation of such training often proves to be ad hoc, and
      may lack educational value. UK training faces challenges as a result of reduced
      hours of work, more structured and intensive educational needs, and pressures of
      increasing clinical demand. A plethora of new 'trust' posts have developed, often
      with limited educational value, creating a risk that training quality for
      overseas doctors is reduced. Against this background, such posts can be used to
      create international training partnerships such as that at Sherwood Forest
      Hospitals NHS Trust (SFHT), providing high-quality general and specialty
      training. Given the success of this strategy, it would be desirable for other UK
      trusts to provide similar schemes offering specialties not covered at SFHT.

PMID- 15847005
TI  - Urbanisation and health.
AB  - The effect on health of urbanisation is two-edged. On the one hand, there are the
      benefits of ready access to healthcare, sanitation, and secure nutrition, whilst
      on the other there are the evils of overcrowding, pollution, social deprivation,
      crime, and stress-related illness. In less developed countries, urbanisation also
      opens the door to 'western' diseases, including hypertension, heart disease,
      obesity, diabetes and asthma. Here we review some of the health-related aspects
      of urbanisation, and comment on strategies designed to improve urban health.
      Because there is such a clear divide between the long process of urbanisation in
      industrialised western nations and the relatively recent explosive expansion in
      resource-poor countries, they are discussed separately.

PMID- 15847006
TI  - Tissue-specific Cushing's syndrome uncovers a new target in treating the
      metabolic syndrome--11beta-hydroxysteroid dehydrogenase type 1.

PMID- 15847007
TI  - Gut feeling--the secret of satiety?
AB  - The worsening global epidemic of obesity has increased the urgency of research
      aimed at understanding the mechanisms of appetite regulation. An important aspect
      of the complex pathways involved in modulating energy intake is the interaction
      between hormonal signals of energy status released from the gut in response to a
      meal, and appetite centres in the brain and brainstem. In particular, the gut
      peptides cholecystokinin, peptide YY, glucagon-like peptide 1, oxyntomodulin and
      pancreatic polypeptide have been implicated in signaling satiety post-prandially.
      The ultimate goal of work in this field is the development of effective
      treatments for obesity, and manipulation of these gut-brain axes offers
      potentially useful strategies for the conquest of this significant cause of
      morbidity and mortality and future burden on healthcare systems worldwide.

PMID- 15847008
TI  - The mummy state.

PMID- 15847009
TI  - Alcohol-related harm--a growing crisis: time for action.

PMID- 15847010
TI  - Diagnosis and management of vertigo.
AB  - Vertigo is an illusion of rotation due to a disorder of the vestibular system,
      almost always peripheral. In the history it must be distinguished from pre
      syncope, seizures and panic attacks. A single attack of acute, isolated
      spontaneous vertigo lasting a day or more is due either to vestibular neuritis or
      cerebellar infarction; distinguishing between the two requires mastery of the
      head impulse test. Recurrent vertigo is mostly due to benign paroxysmal
      positioning vertigo (BPPV), Meniere's disease or migraine. With a good history, a
      positional test, an audiogram and a caloric test, it is usually possible to
      distinguish between these. BPPV is the single most common cause of recurrent
      vertigo and can usually be cured immediately with a particle repositioning
      manoeuvre. Posterior circulation ischaemia very rarely causes isolated vertigo
      attacks and when it does the attacks are brief and frequent and the history is
      short.

PMID- 15847011
TI  - Results of investigations on Gulf War veterans.
AB  - Investigations were undertaken on veterans of the Gulf conflict of 1990/91 at the
      Gulf Veterans' Medical Assessment Programme (GVMAP), to determine whether routine
      investigations should be carried out on these veterans. Blood investigations were
      analysed of a 10% random sample of veterans and also of two veteran groups--one
      group was well (asymptomatic) and the other unwell (post-traumatic stress
      disorder). Neurological investigations were carried out as well as 1,000
      ultrasound studies and 3,000 ECGs. Almost all blood tests proved normal. The only
      significant differences found between the two groups were for the
      alanine/aspartate transaminase and gamma glutamyl transaminase values, where
      there were more abnormal findings in the unwell group. Abnormal, but expected,
      neurological investigations were found in those referred for these tests.
      Ultrasound abnormalities were related to known established clinical diagnoses,
      apart from three cases. ECG abnormalities were only present in those with known
      clinical diagnoses. It was concluded that reducing the number of investigations
      would not only be cost effective but should help to lessen veterans' anxieties.

PMID- 15847012
TI  - Emergency medicine.

PMID- 15847013
TI  - Prophylaxis and treatment of infective endocarditis in adults: a concise guide.

PMID- 15847014
TI  - Prophylaxis and treatment of infective endocarditis in adults: a concise guide.

PMID- 15847015
TI  - CME on infection--management of meningitis.

PMID- 15847016
TI  - The Assisted Dying for the Terminally Ill Bill 2004.

PMID- 15847017
TI  - The Assisted Dying for the Terminally Ill Bill 2004.

PMID- 15847019
TI  - Hippocratic oaths: medicine and its discontents.

PMID- 15847018
TI  - The Assisted Dying for the Terminally Ill Bill 2004.

PMID- 15847020
TI  - Chasing ideas: clinical research in the NHS.

PMID- 15847021
TI  - European Residents Exchange Scheme--new centres needed.

PMID- 15847022
TI  - Survey of flexible working amongst specialist registrars and consultants in
      respiratory medicine in the UK.

PMID- 15847023
TI  - Habilitation in practice.

PMID- 15847024
TI  - Tsunami--an Indian perspective: tidal wave health issues from India.

PMID- 15847025
TI  - Association of small dense LDL with coronary artery disease and diabetes in urban
      Asian Indians - the Chennai Urban Rural Epidemiology Study (CURES-8).
AB  - OBJECTIVE: Earlier studies in Europeans have identified small dense LDL to be
      associated with coronary artery disease and diabetes. In this study we assessed
      the association of small dense LDL with diabetes and CAD in Asian Indians.
      METHODS: Study subjects were selected from the Chennai Urban Rural Epidemiology
      Study (CURES), a population based study on representative sample of Chennai city
      in southern India. Group 1:non-diabetic subjects (n = 30); Group 2: diabetic
      subjects without CAD (n = 30); Group 3:diabetic subjects with CAD (n = 30). LDL
      subfractions were estimated using LipoPrint LDL system. LDL subfractions 3 and
      above, defined as small dense LDL was summed up to determine the overall small
      LDL. 75th percentile of the overall small dense LDL in non-diabetic subjects was
      used as a cut-off for defining elevated levels of small dense LDL. RESULTS: The
      mean age of the study subjects was not significantly different among groups.
      Overall small dense LDL was significantly higher in diabetic subjects with CAD
      (16.7 +/- 11.1 mg/dl, p < 0.05) and without CAD (11.1 +/- 8.0 mg/dl, p < 0.05)
      compared to non-diabetic subjects without CAD (7.2 +/- 6.8 mg/dl). Small dense
      LDL showed a positive correlation with fasting plasma glucose (r = 0.252, p =
      0.023), HbA1c (r = 0.281, p = 0.012), total cholesterol (r = 0.443, p < 0.001),
      triglycerides(r = 0.685, p < 0.001), LDL(r = 0.342, p = 0.002), total
      cholesterol/HDL ratio (r = 0.660, p = < 0.001) and triglycerides/HDL ratio(r =
      0.728, p < 0.001) and a negative correlation with HDL cholesterol (r = -0.341, p
      = 0.002) and QUICKI values (r = -0.260, p = 0.019). ROC curves constructed to
      predict elevated small dense LDL ((9.0 mg/dl) revealed that triglycerides/HDL
      ratio and total cholesterol/HDL ratio had higher AUC values compared to other
      parameters. A triglycerides/HDL ratio of 3.0 had the optimum sensitivity (80.0%)
      and specificity (78.0%) for detecting elevated small dense LDL. CONCLUSION: This
      data suggests that in Asian Indians, small dense LDL is associated with both
      diabetes and CAD and that a triglycerides/HDL ratio (3.0 could serve a surrogate
      marker of small dense LDL.

PMID- 15847026
TI  - Acute Intermittent Porphyria in a Kumhar community of Western Rajasthan.
AB  - OBJECTIVE: To know the current magnitude of the occurrence of Acute Intermittent
      Porphyria in Kumhar community of a part of Western Rajasthan. MATERIAL AND
      METHODS: This is a cross sectional study of rural community of Kumhars of Bikaner
      district of Western Rajasthan. The households of kumhar community were
      approached. Besides recording other information and examination details, their
      urine samples were subjected to Watson-Schwartz Test. RESULT: 1237 subjects out
      of a total of 2385 kumhar population distributed among 20 randomly selected
      villages of Bikaner district could be studied. The prevalence of AIP was
      estimated to be 1.16%. (CI=0.012 +/- 0.0005), showing higher prevalence than the
      earlier reported studies. The cases exhibited varied symptomatology. Overall
      preponderance was in favor of females (2:1) and majority of cases (38.9%) were
      found in the age group of 20-29 years. Average age of manifestation was 24.5 +/-
      4.8 years. A follow up was also done to know the disease consequences, if any.
      CONCLUSIONS: The study finds higher prevalence of the disease and as such
      warrants a need for generating awareness among the families of cases in the
      specific caste group in the study area for early detection and better management
      of the disease.

PMID- 15847027
TI  - Study of bone marrow abnormalities in patients with HIV disease.
AB  - AIM: Present work was carried out to study the bone marrow abnormalities in
      patients with HIV/AIDS and to find their association with peripheral
      hematological abnormalities. METHODS: Seventy four patients of HIV/AIDS were
      included in the study. The patients had anemia, leucopenia, thrombocytopenia or
      pyrexia of unknown origin (PUO) as indications for bone marrow examination. A
      complete blood count, relevant biochemical investigations, HIV RNA load and CD4
      positive lymphocyte counts were done, besides a thorough history and clinical
      examination. HIV positive patients were classified as those having AIDS and those
      without AIDS according to NACO criteria. RESULTS: Majority of patients (72.9%)
      had AIDS. Bone marrow was normocellular in 78.95% of non-AIDS and 74.55% of AIDS,
      hypocellular in 5.26% of non-AIDS and 7.27% of AIDS, hypercellular in 15.79% of
      non-AIDS and 18.18 % of AIDS patients. Myelodysplasia was present in 21.05% of
      non AIDS and 36.46% of AIDS and the most common series affected was granulocytic
      (15.79% of total in non-AIDS and 30.9% in AIDS). Dysplasia was statistically
      significantly associated with lower CD4 count (p = 0.031) and anemia (p = 0.013).
      Myelodysplasia was apparent even before patients developed anemia (16.67%).
      Increased plasma cells in bone marrow were observed in 57.89% of non-AIDS and
      65.45% of AIDS, whereas decreased lymphoid cells were seen in 36.84% of non AIDS
      and 60.00% of AIDS patients. CONCLUSIONS: Myelodysplasia is found in 32.43% of
      cases of HIV/AIDS and is more common in AIDS than in non AIDS patients.
      Granulocytic series is most commonly associated with evidence of dysplasia.
      Myelodysplasia is more common in patients with CD4 count < 200/microl and in
      patients with anemia. 54.05% of patients had decreased lymphoid cells in bone
      marrow and it was more commonly seen in AIDS than in non AIDS.

PMID- 15847028
TI  - Clinical profile of migraineurs in a referral centre in India.
AB  - BACKGROUND: Migraine is one of the commonest of headache disorders presenting to
      neurologists the world over. Though the precise etiopathogenesis of migraine is
      still not completely understood, there are various studies speculating on the
      role of different genetic loci and various patterns of inheritance. OBJECTIVE:
      The present study was conducted to characterize the migraineurs presenting to a
      referral hospital in India and understand their possible modes of inheritance by
      clinical evaluation of family pedigree. METHODS: A questionnaire based,
      prospective study including consecutive patients was conducted in the department
      of Neurology at a tertiary referral center in India. All patients fulfilling the
      diagnostic criteria for migraine were enrolled and their characteristics noted.
      Other family members of those with a positive history of headache were also
      interviewed. RESULTS: A total of 198 migraineurs were interviewed from March 2001
      to July 2002. The proportion of female migraineurs was higher, comprising 72% of
      the study group, with an average age of onset of symptoms of 23.3 years. The
      characteristics of migraine noted revealed certain rare factors aggravating
      headache. A positive family history of headache was observed in 24.7% of probands
      with a possible maternal inheritance on clinical grounds in 29 of 41 families
      (70.7%). CONCLUSIONS: This is an observational study from an Indian centre on the
      clinical characteristics of migraineurs in India. It revealed that migraineurs
      presented a relatively low frequency of family history of headache. Though a
      definite pattern of inheritance can't be commented on, majority with a positive
      family history of headache had a trend to possible maternal inheritance.

PMID- 15847030
TI  - Systemic cutaneous amyloidosis.

PMID- 15847029
TI  - Troponins: current status in coronary artery disease.
AB  - The acute coronary syndromes (ACS) represent a pathological, diagnostic and risk
      continuum from unstable angina (UA) through myocardial infarction (MI) with or
      without ST segment elevation. The past 12 years have seen extensive
      investigations into the use of various cardiac markers to establish the diagnosis
      and prognosis in ACS and to evaluate perfusion after thrombolysis. The Troponins
      comprise a group of three proteins (C, I and T) which interact with tropomyosin
      to form a troponin-tropomyosin complex. Troponin-T is a structural component of
      the troponin complex and is known to exist in three isoforms. Troponins have both
      diagnostic, post-event risk stratification and prognostic significance. Apart
      from myocardial infarction however they are raised in several conditions like
      Myocarditis, dilated Cardiomyopathy, Severe congestive cardiac failure, severe
      pulmonary embolism with right ventricular strain and Preterm infants with
      respiratory distress. False positives have been reported with Angioplasty,
      cardiac surgery, RF ablation, Allograft rejection following cardiac transplant
      and seropositive rheumatoid arthritis. False negatives have been reported with
      early sampling, early reading, use of wrong anticoagulant, clotted blood,
      careless storage of kits. Significantly, lower troponin values have been reported
      in heparinised plasma than in serum.

PMID- 15847031
TI  - Reverse Madelung deformity.

PMID- 15847032
TI  - Medical philately (medical personalities on stamps)--George Nicholas
      Papanicolaou.

PMID- 15847033
TI  - Neural tube defects: pathogenesis and folate metabolism.
AB  - Neural tube defects (NTDs) are a group of congenital malformations with worldwide
      distribution and complex aetio-pathogenesis. Animal studies indicate that there
      may be four sites of initiation of neural tube closure (NTC). Selective
      involvement of these sites may lead to defects varying from anencephaly to spina
      bifida. The NTC involves formation of medial and dorsolateral hinge points,
      convergent extension and a zipper release process. Proliferation and migration of
      neuroectodermal cells and its morphological changes brought about by
      microfilaments and other cytoskeletal proteins mediate NTC. Genetic, nutritional
      and teratogenic mechanisms have been implicated in the pathogenesis of NTDs.
      Folate is an important component in one carbon metabolism that provides active
      moieties for synthesis of nucleic acids and proteins. Several gene defects
      affecting enzymes and proteins involved in transport and metabolism of folate
      have been associated with NTDs. It may be possible in future, to identify
      individuals at higher risk of NTDs by genetic studies. Epidemiological and
      clinical studies have shown that dietary supplementation or food fortification
      with folic acid would reduce the incidence of NTDs. The protective effect of
      folic acid may be by overcoming these metabolic blocks through unidentified
      mechanisms. Genetic and biochemical studies on foetal cells may supplement
      currently available prenatal tests to diagnose NTDs. Antiepileptic drugs (AEDs),
      particularly valproate and carbamazepine have been shown to increase the risk of
      NTDs by possibly increasing the oxidative stress and deranging the folate
      metabolism. Accordingly, it is recommended that all women taking AEDs may use 1-5
      mg folic acid daily in the pre conception period and through pregnancy.

PMID- 15847034
TI  - Visceral manifestations of von Hippel-Lindau disease: value of ultrasound and CT
      imaging.
AB  - Visceral manifestations of von Hippel-Lindau disease (VHLD) are generally
      asymptomatic and their early detection is of considerable help in the management.
      This communication documents the usefulness of imaging studies in detecting
      visceral manifestations in two cases of VHLD.

PMID- 15847035
TI  - Zolpidem at supratherapeutic doses can cause drug abuse, dependence and
      withdrawal seizure.
AB  - Zolpidem is a non-benzodiazepine hypnotic drug, acts selectively through omega 1
      receptors of GABAA. It is thought to be safer than benzodiazepines but we report
      a case of zolpidem drug abuse, dependence and withdrawal seizure.

PMID- 15847036
TI  - Involuntary jerking of lower half of the body (spinal myoclonus).
AB  - A 55 years old, hypertensive, diabetic lady presented with sudden onset jerky
      movement of lower trunk and legs. It was present both in awake and sleep and got
      aggravated by mental stress as well as sensory stimulation. Examination revealed
      rhythmic jerks affecting muscles of lower abdomen and legs. The lower limbs had
      normal muscle bulk and power, increased tone, exaggerated deep tendon reflexes,
      bilateral flexor plantar response with normal sensory autonomic and cerebellar
      function. Investigations including CSF study, MRI of dorsal spine and NCV were
      normal. A combination therapy with tizanidine, baclofen and clonazepam induced
      gradual improvement within 6 weeks.

PMID- 15847037
TI  - Bilateral intracerebral haemorrhages: an atypical presentation of Japanese
      encephalitis.
AB  - Japanese encephalitis is common human endemic encephalitis seen over various
      parts of the world. Usual presenting features include an encephalitic syndrome,
      symptoms of frontal lobe, basal ganglia and thalamic involvement. Characteristic
      radiological picture is bilateral thalamic and basal ganglia hypo density in the
      CT scan and hypo-intensity in T1 and hyperintensity in T2 weighted image in MRI.
      Very rarely occurrence of bilateral hemorrhage may be seen in these regions. This
      radiological change may be early indicator of the disease before serological
      confirmation by the available diagnostic modalities. In this communication, we
      have reported a case of Japanese encephalitis presented with bilateral basal
      ganglia hemorrhages.

PMID- 15847038
TI  - Refractory thrombocytopenia in antiphospholipid syndrome.
AB  - Thrombocytopenia is the second most common manifestation of antiphospholipid
      syndrome (APS). It is found in approximately 22% of the patients with this
      disease. Often it is not severe, platelet counts usually range between 50 x
      10(9)/L and 150 x 10(9)/L without bleeding problems. Yet, it does not protect
      patients against thrombotic events. It rarely requires treatment and, due to
      similarities to idiopathic thrombocytopenic purpura (ITP), similar treatment
      rules usually apply. In this report two patients with APS are described who
      presented with severe thrombocytopenia that did not respond to standard treatment
      regimen namely glucocorticoids (GC) followed by intravenous immunoglobulin
      therapy (IVIG). Splenectomy had to be resorted to relieve the condition.

PMID- 15847039
TI  - Percutaneous closure of iatrogenic femoral arteriovenous fistula using
      endovascular covered stent.
AB  - Local complications after femoral arterial catheterization, such as hematomas,
      pseudoaneurysms, arteriovenous fistulas (AV fistulas), and arterial occlusions,
      are becoming more common, with the growing number of complex invasive procedures
      being undertaken, especially in older and sicker patients. Newer percutaneous
      techniques are being developed to treat these. Covered stents are an effective,
      safe, and less invasive way to deal with pseudoaneurysms and AV fistulas. This
      case report highlights the application of this technique to treat an iatrogenic
      femoral AV fistula in a 69 years male.

PMID- 15847040
TI  - Sjogren's syndrome presenting with interstitial lung disease.
AB  - We report a patient of primary Sjogren's syndrome presenting with interstitial
      lung disease. The clinical picture was dominated by respiratory symptoms leading
      to a delay in diagnosis.

PMID- 15847041
TI  - Chemotherapy-induced palmer planter erythrodysesthesia.
AB  - We report a case of palmar plantar erythrodysesthesia (PPE) in a case of acute
      lymphoblastic leukemia treated with VALP regime. The treating physician must be
      aware of this uncommon complication of chemotherapeutic agents to avoid
      unnecessary investigations.

PMID- 15847042
TI  - Use of metformin in pregnancies with diabetes: a case series from India.

PMID- 15847043
TI  - Valproate-induced hyperammonemic encephalopathy.

PMID- 15847044
TI  - Hyperkalemia--an uncommon cause for flaccid quadriparesis.

PMID- 15847045
TI  - Leptospirosis with transverse myelitis.

PMID- 15847046
TI  - Conjunctival mass: rare site of extramedually relapse in childhood acute
      lymphoblastic leukemia.

PMID- 15847047
TI  - Three year study of antibiotic resistance in acinetobacter species isolated from
      clinical specimens.

PMID- 15847048
TI  - Bilateral ptosis following wasp sting.

PMID- 15847049
TI  - New global perspectives on eating disorders.

PMID- 15847050
TI  - The meaning of 'self-starvation' in impoverished black adolescents in South
      Africa.
AB  - Recent surveys in South Africa have demonstrated that disordered eating is
      equally common among black and white female students. Self-report measures have
      been used in these surveys to establish levels of disordered eating. One study in
      Tanzania, where a two-stage design was implemented, showed that upon interview
      the majority of participants did not present with disordered eating. The absence
      of two-stage studies in South Africa brings into question some of the findings
      from these surveys. In the present study, we surveyed a sample of black and white
      high school students in South Africa to establish the prevalence of disordered
      eating. In the second phase of this study, we attempted to interview those black
      students from one particular school who scored high on the eating disorder
      measures. This process proved both challenging and elucidating. While a
      significant number of young black females endorsed eating disorder symptoms on
      self-report, interviews with some participants showed that self-starvation and
      related symptoms had a different meaning from what we would typically expect from
      someone with an eating disorder. Consequently, this study highlights the need to
      revisit the methods typically employed in cross-cultural research in eating
      disorders. Careful consideration of a variety of cultural factors that may alter
      the meaning of standard measures is called for.

PMID- 15847051
TI  - Not your "typical island woman": anorexia nervosa is reported only in subcultures
      in Curacao.
AB  - Anorexia nervosa (AN), once thought to be a problem of wealthier, Western
      countries has now been documented in survey studies and case reports across
      geographic and economic groups; however, few epidemiological studies including
      interview have been done on these populations. We report on a comprehensive study
      on Curacao, a Caribbean island in economic transition, where the majority of the
      population is of predominantly black African origin. As part of an
      epidemiological study on the island of Curacao indigenous cases of AN were
      identified. Participants were interviewed and asked to complete standardized
      measures of eating behaviors and cultural attitudes. In addition, matched
      controls completed the same measures and were seen in a focus group to assess
      their knowledge of eating disorders and perceived current and future challenges
      to young Curacao women. Six of the nine indigenous cases of AN were successfully
      traced; all were of mixed race. No cases of anorexia were found among the
      majority black population. The women with AN were from the high-education and
      high-income sectors of the society and the majority had spent time overseas. The
      women with a history of anorexia reported higher levels of perfectionism and
      anxiety than the matched controls. All of the women reported challenges to
      maintaining an active professional and personal life and viewed themselves as
      different from the norm. Women who presented with AN evidenced vulnerability to a
      triple threat to identity formation: (1) they were of mixed race, aspiring to fit
      into the mobile elite (and mostly white) subgroup while distancing themselves
      from the black majority; (2) they had the means for education and travel that
      left them caught between modern and traditional constructs of femininity; and (3)
      they had lived overseas, and therefore struggled upon reentry with the
      frustrations of what was possible within the island culture. The race, class and
      overseas exposures of the women with anorexia were anything but typical on the
      island. Cases of anorexia in other developing countries may similarly be limited
      to specific subgroups, which require specialized treatment and planning efforts.

PMID- 15847052
TI  - The rise of eating disorders in Japan: issues of culture and limitations of the
      model of "westernization".
AB  - As the first non-Western nation in contemporary history to become a major
      industrialized economic power, Japan is central to the debate on cultural
      relativism in psychiatric nosologies, and the study of eating disorders in Japan
      contributes to the complex discussion of the impact of culture and history on the
      experience, diagnosis and treatment of such disorders (R. Gordon 2001; Palmer
      2001). Without question, the rise in eating disorders in Japan correlated with
      increasing industrialization, urbanization, and the fraying of traditional family
      forms following World War II. While the case of Japan confirms that the existence
      of eating disorders appears to be linked with these broader social
      transformations, it also points to the importance of specific cultural and
      historical factors in shaping the experience of eating disorders. In this
      article, we explore two particular dimensions of culture in contemporary Japan:
      (1) gender development and gender role expectations for females coming of age;
      and (2) beauty ideals and the role of weight and shape concerns in the etiology
      of eating disorders. Our analysis of these dimensions of culture, and the data
      accruing from empirical and qualitative research, reveal limitations to the model
      of "Westernization" and call for a more culturally sensitive search for meaning
      in both describing and explaining eating disorders in Japan today.

PMID- 15847053
TI  - Television, disordered eating, and young women in Fiji: negotiating body image
      and identity during rapid social change.
AB  - Although the relationship between media exposure and risk behavior among youth is
      established at a population level, the specific psychological and social
      mechanisms mediating the adverse effects of media on youth remain poorly
      understood. This study reports on an investigation of the impact of the
      introduction of television to a rural community in Western Fiji on adolescent
      ethnic Fijian girls in a setting of rapid social and economic change. Narrative
      data were collected from 30 purposively selected ethnic Fijian secondary school
      girls via semi-structured, open-ended interviews. Interviews were conducted in
      1998, 3 years after television was first broadcast to this region of Fiji.
      Narrative data were analyzed for content relating to response to television and
      mechanisms that mediate self and body image in Fijian adolescents. Data in this
      sample suggest that media imagery is used in both creative and destructive ways
      by adolescent Fijian girls to navigate opportunities and conflicts posed by the
      rapidly changing social environment. Study respondents indicated their explicit
      modeling of the perceived positive attributes of characters presented in
      television dramas, but also the beginnings of weight and body shape
      preoccupation, purging behavior to control weight, and body disparagement.
      Response to television appeared to be shaped by a desire for competitive social
      positioning during a period of rapid social transition. Understanding
      vulnerability to images and values imported with media will be critical to
      preventing disordered eating and, potentially, other youth risk behaviors in this
      population, as well as other populations at risk.

PMID- 15847054
TI  - A "coca-cola" shape: cultural change, body image, and eating disorders in San
      Andres, Belize.
AB  - Eating disorders have been associated with developing nations undergoing rapid
      social transition, including participation in a global market economy and heavy
      media exposure. San Andres, Belize, a community with many risk factors associated
      with the cross-cultural development of eating disorders, has shown remarkable
      resistance to previously documented patterns, despite a local focus on female
      beauty. Drawing on longitudinal person-centered ethnography with adolescent
      girls, this article examines why this community appears exceptional in light of
      the literature. First, community beauty and body image ideals and practices are
      explicated. Then, a protective ethnopsychology is proposed as a key mediating
      factor of the rapid socio-cultural change among young women. Finally, possible
      nascent cases of eating disordered behavior are discussed in light of their
      unique phenomenology: that is, having to do more with economic opportunity in the
      tourism industry and less with personal distress or desire for thinness. Close,
      meaning-centered examination of eating and body image practices may aid
      understanding and prevention of eating disorders among adolescents undergoing
      rapid social change in situations of globalization and immigration.

PMID- 15847055
TI  - Commentary: Globalization, culture, body image, and eating disorders.

PMID- 15847056
TI  - Commentary: Towards a clinical ethnography.

PMID- 15847057
TI  - Commentary: Eating disorders and the problem of "culture" in acculturation.

PMID- 15847058
TI  - Engaging culture: an overdue task for eating disorders research.

PMID- 15847059
TI  - Intracellular cytokine patterns of peripheral blood T cells as a useful indicator
      of activeness of Crohn's disease.
AB  - Recently, the alteration of peripheral T cells has become a focus of attention in
      research on Crohn's disease (CD). To examine the characteristics of peripheral T
      cells in CD patients, we analyzed the expression of a memory T cell marker
      (CD45RO(Bright)CD3+) and the cytokine production by peripheral helper and
      cytotoxic T cells in patients with CD. With the use of monensin to prevent the
      secretion of cytokines under stimulation, we measured the count of intracellular
      cytokine-positive cells for production of interferon (IFN)-gamma, tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-6, IL-10, and granulocyte
      macrophage colony stimulating factor (GM-CSF) in the peripheral T cell population
      using flow-cytometry. The counts of lymphocytes, T cells, and helper T cells in
      patients with CD were significantly lower than in normal volunteers. Although no
      difference in the counts of lymphocytes, total T cells, helper and cytotoxic T
      cells was observed, the counts of intracellular cytokine producing helper T cells
      in IFN-gamma, TNF-alpha or GM-CSF were significantly higher in active cases than
      in quiescent cases. These results suggest that stable CD patients are
      immunosuppressive, and activation of some kinds of T-cells, especially Th1
      associated cytokine producing T-cells, correlate with disease progression. Th1
      associated cytokine analysis of peripheral T cells may be one of the useful
      markers to evaluate the activeness of Crohn's disease.

PMID- 15847060
TI  - Multi-target models and their application to data analysis of cellular mortality
      due to radiation exposure.
AB  - We consider multi-target models for use in analyzing data of the dose-response
      relationship. The target sizes we are concerned with here are both homogeneous,
      as assumed in the classical model, and heterogeneous, as simplified using
      geometric progression. We apply two models for establishing the multi-target
      models: a Poisson regression model constructed by assuming that the response
      variable Y follows Poisson distribution, and a gamma-frailty model as a Poisson
      mixture model derived by adding random common risks having a gamma distribution.
      Applying these models to experimental data relating the effects of miso
      fermentation-stages on the survival rate of cells of intestinal crypts of mice
      exposed to radiation yielded the result that there were substantial frailties
      associated with all miso fermentation-stages. Short-term and medium-term
      fermented miso provided similar effects, whereas long-term fermentation had the
      lowest-relative risk value, indicating a significant protection of the crypts
      against exposure effects. A gamma-frailty model based on heterogeneous target
      size was more suitably applied when there were at least 3 dead stem cells having
      10 target genes.

PMID- 15847061
TI  - Attenuation of telomerase activity by hammerhead ribozymes targeting human
      telomerase RNA and telomerase reverse transcriptase in pancreatic carcinoma
      cells.
AB  - In cancer gene therapies, it is ideal to target tumor-specific genes. Since
      telomerase is activated in almost all cancer cells but not most somatic cells, it
      is considered as one of the favorite targets for cancer gene therapies. Ribozymes
      are catalytic RNA molecules with site-specific endoribonuclease activity. In the
      present study, we designed hammerhead ribozymes against human telomerase RNA
      (hTR) and human reverse transcriptase subunit (hTERT) to evaluate their effect on
      the attenuation of telomerase in the pancreas cancer cell line, PK-8. Hammerhead
      ribozyme targeting hTR depressed the level of telomerase activity in PK-8 cells.
      pRc-hTR vector with ribozyme targeting hTR and pRc-hTERT vector with ribozyme
      targeting hTERT mRNA were transfected into PK-8 cells and depressed telomerase
      activity and target RNA, but in pRc-hTR transfectant, hTERT mRNA expression was
      slightly upregulated and in pRc-hTERT transfectant hTR expression was also
      slightly upregulated. These findings indicate the co-regulation of hTR and hTERT
      mRNA expression in cancer cells. Extrachromosomal replicational vector, pCEP4,
      containing ribozyme targeting hTERT mRNA showed the most effective inhibition of
      telomerase activity, suggesting that the continuous effect of ribozyme is
      necessary to inhibit telomerase activity. Since the level of hTERT mRNA
      expression is less than that of hTR expression in cancer cells, ribozyme
      targeting hTERT mRNA might be a more useful therapeutic strategy for cancer gene
      therapy. Moreover, the co-regulation of hTR and hTERT mRNA expression in cancer
      cells to maintain the levels of telomerase activity suggested that the strategy
      of inhibiting hTERT mRNA and hTR simultaneously has a powerful potential as a
      gene therapy for targeting human telomerase.

PMID- 15847062
TI  - Echo-guided identification of key lumbar arteries for the spinal cord:
      preliminary study in the canine model.
AB  - Although identification of the key artery that perfuses the spinal cord is
      essential to avoid occurrence of paraplegia after surgery on the thoracoabdominal
      aorta, reliable and noncomplicated measures are not yet available. A new method
      of determining it by using echocardiography with a saline injection into the
      lumbar artery was evaluated for feasibility and adequacy in a canine model. In
      two mongrel dogs, the abdominal aorta was opened and saline was directly injected
      into the lumbar arteries while the spinal cord was visualized by echocardiography
      through the intervertebral disc. When the echogenic or Doppler signal was
      detected in the spinal cord, the particular lumbar artery was determined as
      "positive", or as "negative" when the signal was not detected. After the dog was
      sacrificed, red resin was injected into the "positive" arteries and blue resin
      into the "negative" arteries. In the extracted spinal cord, the anterior and
      posterior spinal arteries were filled with red resin, rather than with blue
      resin, to indicate that the key arteries were correctly identified. There were
      multiple "positive" arteries, which were mainly located on the left side and
      accounted for approximately one-third of the entire lumbar arteries. The
      "negative" arteries mainly perfused the muscles around the vertebra. Injected
      resin came out of the adjacent lumbar arteries of the same category, suggesting
      that communication is present among the positive arteries, but independently of
      that among the negative arteries. Echo-guided identification of key arteries is
      technically feasible and correctly determines the key arteries in this
      preliminary canine model.

PMID- 15847063
TI  - Progressive central nervous system metastases in responder patients for outside
      central nervous system metastases on trastuzumab-based therapy--report of two
      cases of refractory breast cancer.
AB  - We report two cases of central nervous system (CNS) metastases during systemic
      response to trastuzumab in combination with chemotherapy for refractory breast
      cancer. The patients responded to trastuzumab in combination with chemotherapy.
      During combination treatment, the patients developed cerebellar metastases. A
      follow-up computed tomography scan revealed that their diseases continued to
      respond outside the CNS. These cases suggest that the failure of trastuzumab to
      cross the blood-brain barrier may compromise its overall effectiveness and raises
      the possibility that CNS metastasis may become clinically more significant in
      patients receiving antibody-based therapies, including patients responding to
      therapy outside the CNS. Additionally, repeated stereotactic radiosurgery as
      gammaknife combination therapy synchronously with systematic trastuzumab-based
      therapy was useful for the treatment of metastatic breast carcinoma.

PMID- 15847064
TI  - European position paper on rhinosinusitis and nasal polyps.

PMID- 15847065
TI  - [Assessment of furnished cages for laying hens--development for small aviaries].
AB  - Observations on six farms keeping laying hens in furnished cages showed that hens
      accepted the installations of this new housing type. Behaviours indicating that
      the adaptations of hens were problematic have not been observed. Locomotion and
      dust bathing in some groups occured as not sufficient. Lighting was too low and
      affected expressions of behaviour patterns. For further developments are proposed
      more usable space per bird and a different placement of perches. Dust bathes
      should be utilized permanently and should contain sufficient amount of litter.

PMID- 15847066
TI  - [A procedure to test and approve standard farm equipment in respect to animal
      welfare].
AB  - Since several years, there are claims from various sides to introduce and
      establish test methods and approval procedures concerning mass-producted standard
      farm equipment and husbandry systems in Germany. Such a procedure should be
      closely related to practical conditions, feasible and promoting innovation. The
      aim is to improve animal welfare, to relieve the authorities of single case
      testing and to create legal confidence for both, manufacturers and livestock
      owners.

PMID- 15847067
TI  - [Animal welfare aspects regarding the raising of breeding ostriches in Germany].
AB  - The commercial housing of African Ostriches in Germany for the breed and meat
      production still represents a disputed topic under the criterion of the animal's
      welfare. Above all critics state that the frequently wet-cold weather in Germany
      impairs the well-being and health of the animals. So far however there are just a
      few scientifically documented data about requirements for housing conditions of
      ostriches in Central Europe and thus hardly answers whether housing in Germany is
      possible under the criteria of the animal's welfare. This study tried to evaluate
      ostrich housing under South German climatic conditions (Rhine level), on the
      basis of behavioral observations of breeding ostriches. The use of the stable and
      the influence of different climatic parameters on the behavior were considered.
      In addition the behavior of 18 adult animals in 5 breeding groups from January to
      December 2002 was observed. Parallel various climatic data were raised. The
      housing of the animals took place in open stables with unrestricted pasture
      possibility. The ostriches reacted in their behavior to different climatic
      conditions. Particularly at cold weather and adverse soil conditions they used
      the open stable increasingly as weather protection. In addition, with increased
      wind velocities the animals spent more time in the stables. The daily amount of
      precipitation showed no influence on the frequency or duration of the stable use.
      Rainfall did not animate the animals to look for protection within the stable,
      but more to set itself on the ground in the external enclosure. The locomotion
      activity of the animals was strongly in dependence to the reproduction time and
      the territorial behavior and therefore highest in spring. On cold days the
      animals performed their reproduction behavior mainly in the stable. For the
      comfort behaviour distinct weather dependence was seen particularly for sand
      bathing. Warm temperatures and dry sand were the preconditions for it. Regarding
      the results it seems, that with the conditions existing on the examined farm,
      housing of ostriches under respect of animal welfare in Germany is possible. New
      regulations are to be demanded, adjusted to the newest level of knowledge about
      ostrich husbandry, with requirements for care, support, accommodation and
      nutrition of the animals as well as about the qualification of the owners. An
      occasional hobby animal husbandry limited to few single ostriches is to be
      rejected. Further scientific investigations at other farms, possibly also under
      variable climatic conditions are however necessary.

PMID- 15847068
TI  - [Animal welfare legal aspects of rodeo events].
AB  - Rodeo events have been criticised by animal welfare organisations as being
      adverse to animal protection, for years. This was the motive for TVT to put
      several of these criticised disciplines to evaluation in terms of animal
      protection aspects. For that purpose, various rodeo events were visited, and
      videotaped material of almost all events, which had taken place in Germany in
      2003 and 2004, was evaluated. Rodeo events are subject to and 11, sec.1, No. 3d,
      German Animal Protection Act, which implies compulsory accreditation. In the
      scope of such events, causing any sort of pain and suffering (and 3 No. 6 German
      Animal Protection Act) is prohibited. A proof of the severity of the pain caused,
      is therefore no necessity. For the "critical" disciplines "Bare Back Riding" and
      "Saddle Bronc Riding" a so called "flank" is used. A flank is a leather strap,
      fastened to the sensitive parts of the horse skin, (around the flanks,) which is
      tightened to a maximum as soon as the horse is released from the starting box.
      Analysis show, that the strap has to be seen as the trigger for the wanted kow
      tow. The different coping strategies shown by the animals prove that the leather
      strap is an apt instrument to cause pain and/or suffering (anxiety/fear/stress)
      in horses. Bull riding, instead, showed that the rider has to be seen primarily
      as the trigger for defence behaviour, here. In consideration of the current legal
      position and taking ethic principles into account, it seems appropriate to only
      authorise rodeo events under the condition of a flank strap ban. Bull riding
      should be banned in general.

PMID- 15847069
TI  - [Euthanasia of small rodents. Reasons, methods and assessment of animal welfare].
AB  - Euthanasia of vertebrates requires a high extend of responsibility and specified
      knowledge, according to the regulations of the German Animal Welfare Act. Every
      day innumerable vertebrates, including small rodents, were euthanized from
      various reasons. Only part of these cases are supervised by official authorities.
      In this paper the available methods of euthanasia, especially of small rodents,
      are explained and an assessment under the aspects of animal welfare is
      undertaken.

PMID- 15847070
TI  - [Consequences of the judgment of the Federal Constitutional Court on the fighting
      dog problem].
AB  - The Federal Constitutional Court decided with its "Dangerous dog-judgment" about
      the constitutional complaint of 53 dog breeders on the federal act combating
      dangerous dogs. This judgment was a so-called Pyrrhic Victory for the appellants.
      The Court declared the legislative competence of the federal level in this issue
      for null and void. But the statutory prohibition for breeding Pitbull-Terrier-,
      American Staffordshire-Terrier-, Staffordshire-Bullterrier-, Bullterrier-races
      and cross breeding out of this dogs will be governed in police laws by the
      Laender finally. The Standing Conference of the Ministers for Internal Affairs
      declared an appropriate recommendation. The use of the category "race" was
      refused by experts in discussions as completely wrong and not acceptable. But the
      Federal Constitutional Court reasons that the legislator can use the category
      "race" within his scope of evaluation and prognostication in accordance with the
      Constitution for the ban of import of dangerous dogs. The Court demands--because
      of the weak data background - that the legislator monitors the legislation, to
      adjust it according to current developments. The Constitutional Court creates
      with the judgment "dangerous dogs" legal certainty. The jurisprudence of the
      administrative courts of the Laender and of the Federal Administrative Court
      based on the category "race" was approved as well as the police laws of the
      Laender dealing with dangerous dogs.

PMID- 15847071
TI  - [Aspects of animal welfare with regard to the production of farmed fish in
      aquaculture systems].
AB  - The most important aspects on animal welfare with reference to fish are presented
      in this paper. World-wide a fast growing trend with regard to the production of
      aquatic organisms in aquaculture systems is observed. For the future an increase
      of the number of basic questions with relevance to animal welfare in this area is
      to be expected. The main precondition for the creation of appropriate welfare
      conditions with regard to the farmed fish species is the optimisation of the
      environmental quality. Careful handling in the course of necessary farming
      activities minimises the appearance of distrees and damages in live fish.

PMID- 15847072
TI  - [The ethics of animal welfare and the ethics of animal protection].
AB  - An argumentational analysis of the German legislation for animal welfare suggests
      that the concept "Ethischer Tierschutz", declared as a state objective in 2002,
      allows the legislative body greater scope than that utilized so far. The
      legislator would, in principle, be able to regulate some problem areas which have
      been repeatedly addressed by the public as well as the ethics. A comparison with
      Switzerland and the EU-member Austria shows that both countries' animal welfare
      legislations already reach beyond a strictly suffering-based protection framework
      by employing additional anthropocentric arguments. The concept "Ethischer
      Tierschutz" would make this approach likewise feasible in Germany.

PMID- 15847073
TI  - [Legal view of treating ownerless, confiscated and lost animals].
AB  - Year after year over 300,000 animals are being brought into the more than 500
      German animal shelters. The majority of these (70%) are lost or confiscated
      animals which will be kept there for a short time. The animal shelter takes care
      of animals which are not their own property. Legally, the communities are
      responsible for the accommodation of lost and confiscated animals. For lack of
      sufficient public animal shelters, the communities regularly assign private
      animal shelters with the accommodation of these animals. In this matter, problems
      arise when it comes to realising the reimbursement of expenditures because
      specific regulations concerning the duration of such duties and the amount of
      refunding do not exist. Even the differentiation between lost animals and
      ownerless animals does not go undisputed. Recently many communities have begun
      refusing the payment of costs for accommodating cats because they are of the
      opinion that these animals were neither lost nor are in a state of emergency. As
      regards feral or ownerless animals, communities are responsible for these in
      order to maintain public security if such animals endanger individual persons or
      the public at large. The accommodation of confiscated animals, especially dogs
      which are dangerous, is very demanding on private animal shelters in terms of
      personal and financial resources. Often the owner of the confiscated animal
      cannot pay the reimbursement of costs or the animal shelter has no chance to
      rehome the animal, because it is sick, old or dangerous. Saving costs by killing
      such animals is forbidden by ethical and legal provisions.

PMID- 15847074
TI  - [Legal action instituted by an association to protect animals--a pleading].
AB  - Initiated by the development of the European Law inside Germany a debate has
      started to implement legal actions instituted by associations. In this connection
      Schleswig-Holstein drafted a legislative initiative for voting at the Federal
      Council. This initiative contains a brought legal action instituted by accepted
      associations, the participation of these associations in specific administrative
      proceedings, and a wide title to disclose. This legal suggestion includes a
      determination of the mandate given by the constitution (para. 20a GG) to protect
      animals.

PMID- 15847075
TI  - [Detection methods of diurnal changes in plasma leptin concentrations].
AB  - OBJECTIVES: The authors evaluated the usefulness of the three mathematical
      methods used to identify pulses in the diurnal rhythm of leptin concentration
      variations in blood serum. DESIGN: In order to perform the evaluation 160 cases
      of computer-aided pulse simulation were used. Also the evaluation of leptin
      concentration variations in 2 healthy women (lean and obese) was made. MATERIALS
      AND METHODS: The following were the parameters used as the basis for defining the
      simulated courses: the average concentration of leptin in 24 hours, the amplitude
      of the diurnal cycle, the number and amplitude of pulses, the error of leptin
      concentration in one sample. In 2 healthy women blood samples (0.5 ml) from
      cubital vein were taken every 10 minutes in 24 hour period. The pulse detection
      was carried out by means of three methods: threshold with auto-correlation,
      cluster method and spectral analysis using the Fourier transform. RESULTS AND
      CONCLUSIONS: According to the results of the simulation it can be suggested that
      the threshold with auto-correlation method is the least sensitive to measurement
      error of leptin concentration. Threshold and cluster method confirmed the pulse
      way of leptin release to circulation in clinical study, but the number of pulse
      occurrences, observed in 24 hour period by means of these methods, was different
      in the same patients (in obese ranged from 8 to 22 and in lean from 12 to 20). It
      was observed that after a meal there was a well-marked pulse of insulin release,
      however, the leptin release pulses were marked in both lean and overweight women
      at random (had no correspondence with insulin pulses).

PMID- 15847076
TI  - [Analysis of treatment outcome in patients with endometrial cancer limited to the
      uterus].
AB  - OBJECTIVES: The aim of study was to analyse results of treatment patients with
      uterine-confined endometrial cancer which underwent surgery and postoperative
      radiotherapy in Center of Oncology in Krakow between 1985 and 1997. MATERIAL AND
      METHODS: The research included a group of 650 women. All patients undergo total
      abdominal hysterectomy with bilateral salpingo-oophorectomy and postoperative
      radiotherapy. 155 patients with intermediate-risk of recurrence (IA-G3, IB-G1,
      G2) received postoperative whole pelvic irradiation only. In the group of 495
      patients with high-risk of recurrence (IB-G3, IC, II) 210 patients received
      brachytherapy vaginal cuff only and 285 patients whole pelvic and vaginal cuff
      irradiation. RESULTS: In the group of patients with intermediate-risk of
      recurrence five NED survival was 93.5%. In the group of patients with high-risk
      of recurrence five NED survival was statistically lower in patients treated with
      brachytherapy vaginal cuff only (83.2% vs. 71.9%). CONCLUSION: In uterine
      confined endometrial cancer patients, with intermediate-risk of recurrence
      treated with surgery and postoperative whole pelvis irradiation, 5-year NED
      survival is above of 90%. In the group of patients with high-risk of recurrence
      the adjuvant treatment of choice is whole pelvic and vaginal cuff irradiation.

PMID- 15847077
TI  - [Recurrence of endometrial cancer after surgical treatment].
AB  - OBJECTIVES: The purpose of the research was to analyze the frequency and location
      of endometrial cancer recurrence in a group of women who underwent surgery due to
      neoplasm and frequency of relaparotomy because of the neoplasm recurrence.
      MATERIALS AND METHODS: 292 women underwent operation in Dept. of Gynecology at
      Medical University of Gdansk due to endometrial cancer in clinical stage IA-IV by
      FIGO 1988 in the years of 1981-1996. All materials were analyzed using Microsoft
      Excel 97. The information was gathered from the following sources: case histories
      Dept.of Gynecology and Dept. of Oncology and Radiotherapy Medical University of
      Gdansk, case histories from Dept.of Radiotherapy Marine Hospital in Gdynia
      Redlowo and questionnaires sent to patients. RESULTS: The mentioned above group
      of 292 women underwent surgery. As far as 233 instances (79.8%) are concerned,
      only hysterectomy with bilateral oophorectomy was used, in 23 situations (7.9%)-
      also the lymph nodes biopsy was performed whereas in 10 cases (3.4%)-
      appendectomy and/or omentectomy. 24 women (8.2%) underwent Wertheim-Meigs
      operation and only 2 patients (0.7%)--with vaginal hysterectomy. 138 women were
      chosen to take part in the next stage of treatment. The regression of neoplasm
      illness was discovered among 13 patients (4.5%) with the apex of vagina being the
      most common place. The result comprised of 6 women--46.1% of all recurrences. All
      regressions happened 1-2 years after surgery. 5-year-survival for patients with
      regression was 23.1% which is 3 women. Relaparotomy due to neoplasm illness took
      part in 9 situations (3.1%). The danger of fatality grew up to 16 month after
      first surgical treatment; after this period of time the risk of dying went down.
      CONCLUSIONS: The recurrence of endometrial cancer can be observed among small
      group of patients (4.5%). When we concentrate the patients with regression of
      neoplasm disease, we can observe a high rate of fatality.

PMID- 15847078
TI  - [Comparative analysis of patients with multiple pregnancy hospitalized at the
      Gynecology and Obstetrics Department of the Medical University of Gdansk in 1981
      1990 and 1991-2000].
AB  - OBJECTIVE: The purpose of this study was to present twinning rates and to compare
      patients with multiple pregnancy delivered at Gynaecology and Obstetrics
      Department of Medical University of Gdansk in 1981-1990 and 1991-2000. MATERIAL
      AND METHODS: A retrospective study of 523 twin births was performed. The analysis
      concerned: maternal age, place of living, education, parity, using of assisted
      reproductive techniques. RESULTS: The incidence of twin pregnancy was 1.0%. The
      percentage of twin deliveries in 1981-1990 was 0.84% and in 1991-2000: 1.28%. The
      number of twin pregnancies depending on maternal age in two periods was analysed.
      The statistically significant differences were observed in maternal age interval
      21-25 years (32.4% in 1981-1990 versus 20.8% in 1991-2000, p=0.01) and in age
      interval < 20 years (3.5% in 1981-1990 versus 8.8% in 1991-2000, p=0.009). There
      were 3.2% patients with multiple pregnancy treated due to infertility in 1981
      1990 and 7.4% in 1991-2000 (p=0.04). CONCLUSIONS: We observed the increase in
      twinning rates in our department. The mean age of patients with multiple
      pregnancy increased. We noticed the increase in number of iatrogenic multiple
      pregnancies.

PMID- 15847079
TI  - [Myasthenia gravis and pregnancy].
AB  - We retrospectively analyzed the course and outcome of pregnancy in a group of 26
      women with myasthenia gravis. Premature births were noted in 7.9% of pregnancies,
      the rate of cesarean section was 15.8%. Neonatal myasthenia was observed in 10
      children born by 5 women (16% of the mothers). There were three neonatal deaths:
      two due to neonatal myasthenia, one in a child born with multiple congenital
      anomalies. Transient exacerbation of MG symptoms was observed during four
      pregnancies (10.5%). MG is not associated with increased risk for MG patient and
      the newborn. Giving birth to one child with transient MG increases the risk of
      transient MG in consecutive pregnancies.

PMID- 15847080
TI  - [The significance of -174G/C polymorphism of the gene coding for interleukin-6 in
      neonatal infections].
AB  - OBJECTIVE: Interleukin-6 (IL-6) is a specific marker of early onset infections in
      the newborns. In recent years it has been suggested that in regulations of IL-6
      activity could play a role the genetic polymorphism (-174G/C) in the promoter
      region of the gene coding for IL-6. The aim of our study was to analyse the
      frequency of -174G/C polymorphism of interleukin-6 gene as a genomic marker for
      individuals at an increased risk of early onset neonatal infection as result of
      intra-amniotic infection (IAI). MATERIAL AND METHOD: A prospective study was
      conducted in 62 newborns treated in University Hospital tertiary neonatal
      intensive care unit. Intrauterine infection was diagnosed in 21 children and 41
      neonates comprised control group. In the both groups we have analysed -174G/C
      polymorphism in the gene coding IL-6 using PCR/RFLP (polymerase chain
      reaction/restriction fragment length polymorphism) assays. RESULTS: We have
      observed the overrepresentation of homozygous genotypes -174C/C in the
      investigated group (9.5% vs. 7.3% in the controls). The frequency of heterozygous
      genotypes -174G/C was higher in investigated group 61.9% than in controls 56.1%.
      Homozygous wild type genotypes for -174G/G were detected in 28.6% and 36.6% in
      investigated group and controls, respectively. These proportions were consistent
      with the Hardy-Weinberg equilibrium. Analysing allelic frequency we have noticed
      overrepresentation of -174C alleles in the investigated group (40.5% vs. 35.4% in
      the controls, O.R. = 1.24, n.s.). CONCLUSION: The presence of the C allele in the
      -174 position in the gene coding for IL-6 could play a role in the pathology of
      neonatal infection following IAI in the mother and probably is connected with
      decreased of immunological reaction.

PMID- 15847081
TI  - [Non Hodgkin lymphoma during pregnancy].
AB  - The coexistence of Non Hodgkin Lymphoma and pregnancy has been rarely reported.
      We are describing the case of 26-year-old pregnant woman, to whom two
      chemotherapy courses were administered because of the lymphoma. In 32 week of
      pregnancy cesarean section was performed due to patient general state worsening.
      Despite of chemotherapy children have been developing well. In the course of
      treatment autologous STEM cell transplant was performed. Since 13 months patient
      has been in remission.

PMID- 15847082
TI  - [Preterm delivery by cesarean section in patient with polycythemia vera].
AB  - Polycythemia vera is a myeloproliferative disease most commonly diagnosed in male
      60-70 years old patients. It is associated with a higher risk of thrombosis and
      bleeding. It is very rarely diagnosed in young patients, and thus only few cases
      of pregnant women have been reported in the literature. These reports show that
      polycythemia vera may have a detrimental effect on outcome of the pregnancy (PIH,
      spontaneous miscarriages, preterm delivery, and stillbirth). We report a 33-year
      old woman with polycythemia vera who underwent caesarean delivery in 34 weeks
      gestation. This case demonstrates fully successful result of our intensive
      perinatal care.

PMID- 15847083
TI  - [Microphthalmos and hypertelorism as diagnostic index in ultrasound diagnosis of
      Fraser syndrome].
AB  - Fraser syndrome is a rare genetic syndrome with abnormalities of the head, lungs,
      kidneys, and limbs. A prenatal diagnosis of FS can be done in families with risk,
      using foetal ultrasonography. However, a wide qualitative and quantitative
      variability of possible abnormalities makes the diagnosis in utero notably
      questionable. We present the results of foetal ultrasonography in a tertigravida,
      had delivered two children with FS. Signs of foetal hypertelorism and
      microphthalmia, both traits typical for FS, were detected based on outer and
      inner orbital diameters and ocular diameters in 28 and 32 weeks of pregnancy. The
      clinical and pathological examinations after birth confirmed the diagnosis of FS.
      Our observation suggests that eye anomalies may prompt the diagnosis of FS even
      if characteristic lung and kidney abnormalities are absent. Therefore, we propose
      to regularly assess eye dimensions and distance, when performing any foetal
      ultrasonography in families with of FS.

PMID- 15847084
TI  - [Gonadotropins and ovarian cancer].
AB  - The ovary is a tissue, which is sensitive to gonadotropins. Gonadotropins
      receptors are present in the epithelium and stroma of the ovary. Data from
      epidemiological study clearly shows, that development of tumor is correlated with
      morphological and biochemical processes taking place in the gonad. The role of
      gonadotropins, as well as the role of their receptors in the proliferation of the
      ovarian tissue was shown. Further research is needed to explain the molecular
      mechanism of gonadotropin activity in ovarian tissue, however the important role
      of gonadotropins in the pathology of ovarian tissue is already well established.

PMID- 15847085
TI  - [Changes to the periodontium in postmenopausal women].
AB  - Few up to date studies on the influence of hormonal replacement therapy (HRT) on
      periodontium has been conducted on small groups of patients and the conclusions
      made may require further investigation on a larger population. It has been widely
      accepted that decreased estrogen levels in postmenopausal women are associated
      with a gradual loss of a bone density and increased risk of a dental loss. Much
      less stress is put however on the fact that the same phenomenon, especially
      suboptimal levels of estradiol, may deteriorate periodontal tissue condition. The
      authors made a literature search on the influence of HRT on periodontium.

PMID- 15847086
TI  - [Role of mycoplasmas in urogenital tract infections and their complications].
AB  - In the literature from recent years it is stressed the significant
      epidemiological and clinical role of the sexually transmitted infections caused
      by so called "new generation" pathogens including mycoplasmas. The paper gives a
      review of the current literature concerning the epidemiology, clinical
      presentation, diagnosis and therapy of the infections of urogenital tract caused
      by mycoplasmas.

PMID- 15847087
TI  - [Economic evaluation of hospital patients].

PMID- 15847088
TI  - [Alcohol sclerotherapy of biliary cysts. Our experience].
AB  - AIM OF THE STUDY: To evaluate if percutaneous ethanol injection treatment,
      introduced twelve years ago as palliative therapy for inoperable hepatocellular
      carcinoma, can be used with curative intent to treat biliary cysts with good
      results. MATERIALS AND METHODS: For the study were observed 13 symptomatic
      patients (M 4; F 9 - age 38-71, medium 54 years). All the patients were treated
      by percutaneous alcoholization under ultrasonographic control. RESULTS: Better
      technique and protocol standardisation give us the possibility to utilise
      percutaneous ethanol injection like a good treatment for symptomatic patients.
      CONCLUSIONS: Easy technique, low cost and very small number of complications
      gives to percutaneous ethanol injection the possibility to become the gold
      standard for the treatment of biliary cysts.

PMID- 15847089
TI  - [Surgical treatment of carotid chemodectoma: our experience].
AB  - Carotid chemodectoma is a tumor that affects the bifurcation of the carotids. It
      is not a frequent event, but it has great importance for surgical and diagnostic
      problems involved. In this article three cases of chemodectoma observed and
      surgically treated are reported.

PMID- 15847090
TI  - [Acute abdomen from ruptured adrenal pheochromocytoma: case report].
AB  - The pheochromocytoma is a very rare neoplasm, which originates in 98% of cases in
      the adrenal medulla; it is often bilateral in familial syndromes. It is more
      frequent in syndromes like MEN2, von Hippel-Lindau disease, and neuofribromatosis
      type 1. In this article the Authors report a case of a young woman with a large
      adrenal pheochromocytoma, that presented by an acute abdomen; the treatment was
      explorative laparotomy with unilateral adrenalectomy. Therapy of this tumour is
      founded on surgery, plus chemiotherapy radiotherapy or treatment with 131I-MIBG
      (iodine-131-metaiodobenzylguanidine in malignant cases (10%). According with the
      absence of a correlation between pathological findings and clinical behaviour, a
      long-term follow up is indispensable.

PMID- 15847091
TI  - [Atheroembolic syndrome due to isolated infrarenal abdominal aorta stenosis and
      endovascular treatment: case report and review of literature].
AB  - One of the most common source of lower extremity atheroembolization is the aorta
      and particularly the infrarenal segment. Complex atherosclerotic plaque can lead
      the patient to gangrene and major amputation. When the origin of embolization is
      a focal lesion, endoluminal methods could be an alternative to surgical
      treatment. Although the experience with aortic stent is limited, the results
      obtained so far seem to be encouraging. The case of a mid-age heavy smoker woman
      with a history of the abrupt onset of painfull cyanotic toes in the left foot and
      subsequent complete gangrene of the first digit in the same foot is herein
      reported. Angiography and CT scan revealed an high-grade calcified aortic
      infrarenal plaque. Because of the discrete characteristic of the lesion, an
      endovascular approach with a Palmaz stent was elected. The stenosis was
      successfully treated: the patient experienced the complete resolution of the toe
      painfull cyanosis within 3 months, the stent remained patent through a 24 months
      follow-up and no subsequent embolic episodes were observed.

PMID- 15847092
TI  - [Uncommon etiology of acute abdomen in pediatric age: the torsion of spleen].
AB  - The torsion of spleen on its vascular shank represents an uncommon problem,
      responsible of acute and chronic pain. The mobile spleen is fixed only through
      hilus vessels the gastrosplenic ligament. The incidence is unknow, greater in the
      male with an M:F ratio 6.1 in the first ten years of life, even if an episode of
      intrauterine torsion has been reported. The diagnosis can be performed with
      ultrasonography, angiography, scintigraphy and CT scan. There are reported two
      cases: male of 2.5 years female of 14 years who presented with recurrent pain to
      the left side, vomit diarrhoea and fever. Objectively a palpable mass was
      present. Ultrasonography and angio-CT scan of abdomen revealed splenomegaly,
      ptosis of the spleen and malrotation with signs of obstruction of the vessels.
      The treatment in both cases was splenectomy. The spleen appeared rotated on its
      shank and increased of volume, deprived of anatomical structures of fixation. The
      histological report confirmed the haemorrhagic infarction. The excessive mobility
      of the spleen, from insufficiency or absence of the ligamentous attachments is
      case of abdominal pain or acute abdomen, that can complicate with the infarction
      of the spleen. Angio-CT scan, in the cases here reported, has shown to greater
      sensibility in comparison to the ultrasonography. The Authors believe that the
      video-laparoscopic splenopexy, when the diagnosis is made of "wandering spleen"
      with painful repeated episodes, can be finalized, to the preservation of organ.

PMID- 15847093
TI  - [The colecistectomy in primary sclerosing cholangitis: case report and review of
      literature].
AB  - Primary sclerosing cholangitis (PSC) is an idiopathic chronic inflammatory
      condition affecting intra- and extra-hepatic biliary system. The aim of this
      study is to stress the importance of cholecystectomy in patients with PSC.
      Consideration should be given to performing a cholecystectomy in PSC patients
      with gallbladder adenomyomas or calculi, even asymptomatic; this happens in
      approximately 15% of cases.

PMID- 15847094
TI  - [Laparoscopic cholecystectomy in uremic patients].
AB  - The aim of this study was to evaluate the effectiveness of the laparoscopic
      cholecystectomy performed in two uremic patients with gallstones. From January to
      July 2004, 15 patients with gallstones underwent to laparoscopic cholecystectomy
      (LC). Two patients had chronic renal failure on haemodyalisis: a symptomatic
      fourty-two old woman, which had primitive hyperparathyroidism and primitive
      hyperaldosteronism, and asymptomatic transplant candidate fifty-five old man. No
      minor and major complications occurred and both patients were discharged 4 days
      after LC. Even in uremic patients the L. C. must be the gold standard for the
      treatment of gallstones both symptomatic and asymptomatic.

PMID- 15847095
TI  - Malignant fibrous histiocytoma of the mesentery: report of two cases and review
      of the literature.
AB  - Malignant Fibrous Histiocytoma (MFH) rarely affects the abdomen and only a few
      cases arising in the mesentery have to date been discovered. In this paper, two
      cases of MFH of the mesentery are described and a review of the literature is
      reported.

PMID- 15847096
TI  - [Hepatic haemorrhage in pregnancy: a case report].
AB  - Spontaneous hepatic haemorrhage in pregnancy (SHHP) is a rare event (1 woman out
      of 15,000). It is generally considered as an advanced state of the
      microangiopathic hemolytic anemia (HELLP, Hemolysis, Elevated Liver enzyme
      levels, Low Platelet count). Furthermore, the HELLP is considered as a different
      form of preeclampsia. The patient, a 33-year-old-woman at 30 weeks' gestation,
      was admitted to hospital for preeclampsia, underwent an emergency Stark caesarean
      section with the extraction of an alive foetus and evidence of massive
      intraperitonal haemorrhage from a large hepatic haematoma. A haemostasis with
      gauzes of Surgicel was performed, with consequent arrest of the haemorrhage.
      After approximately 6 hours, a recurrence of the intraperitonal haemorrhage led
      to a new surgical intervention with hepatic packing with gauzes. After 4 days the
      patient died. The etiopathogenesis of disease is uncertain, both foetal and
      maternal mortality are high, and the slight number of reported cases (27) of SPPH
      from HELLP in international literature offer elements for debate. The following
      points have been put forward: 1. the monitoring of the counts of the platelets
      represent the only valid predictive test of HELLP. These concerned women in the
      third trimester of pregnancy, especially those with a history of preeclampsia; 2.
      the treatment must be immediate, intensive and multidisciplinary, the
      plasmapheresis has remarkably improved the prognosis; 3. surgical treatment
      performed in order to control the SPPH makes use of packing, embolization and/or
      fastening of the common hepatic artery and, in extreme cases, total hepatectomy
      with transplantation. The Authors believe it is useful to suggest a national
      epidemiological research in order to estimate the real incidence of the syndrome
      in Italy and to establish the guidelines for the medico-surgical treatment.

PMID- 15847097
TI  - [Organizational model and clinical evaluation in Day Surgery: our experience].
AB  - Surgical treatments in Day Surgery (DS) are characterised by limited
      hospitalisation during daytime on the base of an organizational model established
      by appropriate protocols. According to it, the patient at low operational risk
      and the patient whose post-operative management is easy is admitted to the
      programme. The Authors report their experience of DS focusing on the surgical and
      anaesthesiological qualifications that help to control the risk factors reducing
      the complications and thus guaranteeing the safety and effectiveness of the
      service.

PMID- 15847098
TI  - [Benign hepatic neoplasms: diagnostic problems and therapeutic approach].
AB  - The liver is one of the main targets of metastases arising from other districts,
      owing to its function to filter the systemic blood circulation and to its being
      the location of primary malignant processes. What is worth pointing out is the
      fact that the prevalence and contemporary prognostic severity of malignant
      tumours of the liver indirectly contributes to the study of benign neoplasms.
      This is due to the urgency of a differential diagnosis, the therapeutic planning
      and the prognosis prediction being rather different. The aim of this study is to
      offer a concise view about clinical arising, diagnostic procedures and
      therapeutic strategy of benign tumours of the liver, areas where surgery plays a
      central role.

PMID- 15847099
TI  - Chondroitin sulphates A, B and C, collagen types I-IV and fibronectin in venous
      sinus of the red pulp in human spleen.
AB  - The morphological relationship of chondroitin sulphates A, B, and C, collagen
      types I-IV and fibronectin in the wall of venous sinuses of the red pulp in human
      spleen has not been a focus of interest among morphologists. Regarding the
      hypothesis that the structure of the spleen lends it the function of a blood
      filter the substances described in our study might play a significant role in the
      functional morphology. Of 146 human spleen surgical specimens, groups of 12
      specimens each were examined under a light microscope using the method of
      antibodies against fibronectin, against collagen types I-IV and against
      chondroitin sulphates A, B, and C. The sections of the red pulp of human spleen
      stained with hematoxylin and eosin provided limited information about the wall of
      the sinuses. Chondroitin sulphates A and B were observed on the surface of sinus
      lining cells (SLC), and fibronectin was detected on the surface of the annular
      fibers. Collagen type 11 was observed almost in the same places as chondroitin
      sulphates A and B. Collagen type IV was present in annular fibers of the wall of
      the sinus and in the basement membrane, like fibronectin. Chondroitin sulphate
      was not present in the walls of sinuses. Binding of antibodies against
      chondroitin sulphate A and against chondroitin sulphate B indicates the presence
      of chondroitin sulfates on the surface of SLC, where they probably play a role in
      helping the human organism to recognize alien and self substances. The presence
      of chondroitin,sulphates A and B probably affects inhibition of binding of cells
      with collagen type I, but not with fibronectin.

PMID- 15847100
TI  - Rheumatic symptoms in patients with human immunodeficiency virus are related to
      levels of tumor necrosis factor-alpha but not to viral load.
AB  - Infection with human immunodeficiency virus (HIV) can lead to osteoarticular
      involvement, usually in the late stages. The pathogenesis of these symptoms has
      usually been attributed to viral load or to dysregulated cytokine production. We
      evaluated the presence of rheumatic symptoms and levels of tumor necrosis factor
      (TNF)-alpha viral load and CD4 count in 46 patients with HIV from southern Italy.
      The prevalence of rheumatic symptoms was 23.9%; CD4 count and viral load
      presented no statistically significant differences between patients with
      rheumatic symptoms and patients without osteoarticular involvement, whereas TNF
      alpha levels were increased in HIV patients with arthralgias compared with those
      in patients without arthralgias (p = 0.02). Evidence that TNF-alpha is increased
      in patients with osteoarticular or soft tissue involvement is a clear index of
      the pivotal role this cytokine plays in the pathogenesis of these manifestations.

PMID- 15847101
TI  - A randomized, open-label, comparative, 6-month trial of oral ultra-low doses of
      antibodies to tumor necrosis factor-alpha and diclofenac in rheumatoid arthritis.
AB  - Artrofoon (oral ultra-low doses of antibodies to TNF-alpha is a novel drug
      approved by the Russian Ministry of Health for the treatment of rheumatoid
      arthritis (RA). The aim of this study was to assess clinical efficacy and safety
      of artrofoon in RA compared with diclofenac. In a 6-month, randomized, open
      label, comparative trial, 60 patients with active RA (eight men and 52 women aged
      23 to 62, mean disease duration 10 years) received artrofoon (8 tablets daily, n
      = 30) or diclofenac (100 mg daily, n = 30). RA signs and symptoms as well as
      serum levels of inflammatory markers were evaluated before treatment and at
      months 1, 3 and 6. Most patients in the artrofoon group showed a 20% improvement
      in major RA symptoms by the end of the study. The clinical effect rose gradually
      reaching maximum at month 6. In the artrofoon group, 57% of the patients achieved
      an American College of Rheumatology (ACR) 20% criteria (ACR20) by month 6 versus
      20% of those receiving diclofenac. In some patients in the artrofoon arm, serum
      proinflammatory cytokine levels significantly decreased (> or = 25% reduction).
      Diclofenac produced a less pronounced clinical effect, and no changes in cytokine
      profile. Unlike conventional nonsteroidal anti-inflammatory drugs, artrofoon
      produced no adverse effects and the overall tolerability and safety were
      excellent. A half-dose treatment with artrofoon (4 tablets daily) was able to
      sustain clinical improvements over a 6-month follow-up period. To conclude,
      artrofoon is a safe and effective treatment for rheumatoid arthritis that acts by
      influencing the inflammatory process.

PMID- 15847102
TI  - Clinical and immunohistochemical study of the effect of a cosmetic product in
      patients with asteatotic eczema.
AB  - Cutaneous xerosis is a common clinical condition associated with an altered
      barrier function of the stratum corneum. Xerotic skin appears dry, rough and
      slightly scaling. Patients complain of pruritus and stinging. Our aim was to
      investigate the clinical effects of a cosmetic ointment (Scherilan) in patients
      with circumscribed senile xerosis (also called asteatotic eczema). Moreover,
      variations in expression of epidermal proteins such as keratin (K)-5 and
      involucrin, detected by immunohistochemistry, were also evaluated before and
      after topical treatment. We enrolled 30 patients (11 males, 19 females) with
      asteatotic eczema. We examined dryness, roughness and desquamation and symptoms
      such as itching and dryness. A score of 0 to 3 was assigned to each of these
      parameters. A biopsy was performed in seven patients before and after a 21-day
      topical treatment. All skin specimens were then immunostained with antibodies to
      K5 and involucrin. At day 7 or 21 of treatment all signs of xerosis and pruritus
      were significantly reduced; furthermore, the reduction increased with the
      duration of therapy. Before treatment K5 was strongly expressed in stratum basale
      (SB) and stratum spinosum (SS), while involucrin was strongly expressed in
      stratum granulosum (SG) and the upper portion of SS. In contrast, after treatment
      immunostaining for K5 was restricted to SB and the lower part of SS, while
      involucrin showed intense staining in SG. We highlight the importance of treating
      cutaneous xerosis with an ointment such as this one, which probably induces an
      increase of lipid content of the SC intercellular matrix.

PMID- 15847103
TI  - Imiquimod 5% cream: a new treatment for Bowen's disease.
AB  - Bowen's disease (BD) is a squamous cell carcinoma in situ. Recent studies suggest
      that human papilloma virus plays an important role in the development of BD. We
      investigated whether imiquimod 5%, a topical immune response modifier, is an
      effective treatment for BD in five immunocompetent patients. The lesions were one
      genital and four extragenital. The frequency of application varied from three
      times weekly up to twice daily, and treatment duration ranged from 8-24 weeks.
      Four patients achieved clinical and histological cure. The patient with the
      genital lesion gained an important reduction in size and infiltration, which
      enabled surgical removal of the remaining lesion with good functional and
      cosmetic result. Our results suggest that topical imiquimod 5% is an effective
      treatment for BD through its viral and antitumor effects.

PMID- 15847104
TI  - [Mesothelioma: the aetiological role of ultrathin fibres and repercussions on
      prevention and medical legal evaluation].
AB  - BACKGROUND: Mesothelioma has until now been considered to be a manifestation,
      occurring in the pleura and/or peritoneum, of the carcinogenic action of the
      total burden of inhaled asbestos fibres, in the same way as lung cancer. Because
      of the pathogenic potential of very low exposure levels, the fact that the onset
      of the neoplasm always occurs in the parietal pleura, and the absence of any
      synergism with smoking, which is typical in the case of carcinoma, it was
      suspected that aetiopathogenetic differences existed but the reasons for such
      differences still could not be explained. In the past experimental results
      indicated the oncogenicity of very thin fibres but mesothelioma in practice was
      not exclusively linked to this specific dimensional size class. OBJECTIVES: The
      paper proposes to take full advantage of the significant knowledge that must
      emerged from research carried out in recent years and use this knowledge to
      reconstruct the mosaic of the aetiopathogenesis of mesothelioma. Due
      consideration will also be given to the consequent new approach required in the
      field of medical-legal evaluation of cases and in the field of prevention.
      RESULTS: The most important knowledge that must today be taken as certain is the
      fact that mesothelioma is not caused, as is the case for asbestosis, by all the
      fibres that are inhaled but only by the ultrathin fraction of these fibres,
      having diameter of 0.2 microm and length of only a few microm. Only fibres of
      this class of size can cross the pulmonary-pleural barrier and are, therefore,
      the causal agent of mesothelioma and other benign pleural manifestations
      (plaques). Moreover the ultrathin fibres that translocate from the lung to the
      pleura are not distributed casually on the parietal and visceral surfaces but
      move over the surfaces, to concentrate around the lymphatic reabsorption stomata
      situated on the parietal pleura. Due to their shape, the fibres cannot easily be
      absorbed into the stoma via the lymphatic flow and so remain clustered for an
      indefinite period of time among the mesothelial cells that surround the stoma.
      The concentration of ultrathin fibres in punctiform areas of the parietal pleura
      and the extremely long biopersistence of the amphiboles now finally explain how
      very low exposures can cause mesothelioma in susceptible subjects and why the
      neoplasm always occurs on the parietal pleura. CONCLUSIONS: In medical-legal
      assessments of cases of mesothelioma the etiological importance of the ultrathin
      fraction of fibres means that any assumption of the disease being avoidable must
      be discarded, at least up to the second half of the 1980s because until then this
      class of fibres, which today must be considered as the true causal agent of the
      neoplasm, was not visible under the optical microscope, nor could such fibres be
      measured or eliminated from the atmosphere of working environments. The filter
      materials available both for fixed ventilation systems and for individual
      protective masks were not able to block the ultrathin fibres and were therefore
      only efficacious for the prevention of asbestosis and probably pulmonary
      carcinoma. It was only with the use of highly efficient HEPA filters and
      "absolute" filters towards the end of the 1980s that efficacious protection
      against all size classes of respirable fibres became possible in industrial
      plants. Preventive measures in the public hygiene area must also take account of
      the aetiological role of ultrathin fibres by making full use of electron
      microscope investigations and by using "absolute" filters for domestic purposes,
      in ventilation systems and above all in the filter systems of the mechanical
      devices used in town street cleaning operations.

PMID- 15847105
TI  - [Prevalence of respiratory symptoms, reduction in lung function and allergic
      sensitization in a group of traffic police officers exposed to urban pollution].
AB  - BACKGROUND: Environmental factors are believed to play a critical role in the
      development of allergic respiratory diseases, such as asthma and rhinitis.
      Particularly, the role of urban pollution in the pathogenesis of these diseases
      is debated. OBJECTIVES: The aim of the study was to investigate whether subjects
      with a well-defined occupational history of exposure to road traffic fumes
      presented an increased prevalence of respiratory symptoms of chronic bronchitis
      (cough), asthma (wheeze), and allergic sensitisation to the most common allergens
      and reduced lung function compared with an unexposed control group. METHODS: The
      study was conducted on 484 traffic police in Catania (465 men and 19 women), with
      a mean age of 45 +/- 7.9 years, who were subdivided into three groups. The first
      group included traffic police assigned to traffic direction, the second group
      included traffic police working in administrative offices, the third group
      included all traffic police who did not fall into the previous groups. In the
      first group, "truly exposed" subjects were identifed as police officers assigned
      to traffic direction in the last 8 years. Similarly, in the second group, "truly
      non-exposed" subjects were identified as police officers working in offices in
      the last 8 years. RESULTS: Statistical analysis showed a significant difference
      in mean age between the truly exposed group and the truly non-exposed group (p <
      0.01). The truly exposed group showed a greater prevalence of symptoms (cough,
      wheeze and dyspnoea), and positive reaction to skin allergy tests compared with
      the "truly non-exposed group", but this increase did not reach statistical
      significance. Alterations of the respiratory function tests were more frequent in
      the non-exposed (14.3%) compared to the exposed group (9.6%). The highest
      prevalence of cough, dyspnoea and wheezing was detected in smokers compared to
      non-smokers and to ex-smokers within each group. CONCLUSIONS: Our results show a
      major prevalence of respiratory symptoms and allergic sensitisation in exposed
      traffic police compared with non-exposed police, although this did not reach
      statistical significance. Further epidemiological studies conducted on larger
      samples are required to better understand the role of road traffic pollution in
      inducing allergic respiratory diseases.

PMID- 15847106
TI  - [A monitoring system for occupational cancer].
AB  - INTRODUCTION: The Italian Occupation and Safety Act (d.lgs 626/94) provided for
      the establishment of a nationwide occupational cancer registry, under the
      National Institute for Occupational Health and Safety (ISPESL), with the aim of
      detecting cancer cases of occupational origin and estimating the influence of
      occupation in cancer causation. METHODS: Information on cancer cases, drawn from
      six Italian population-based cancer registries (CRs of Friuli Venezia Giulia
      Region, Genoa Town and Genoa Province, Macerata Town, Umbria Region, Varese Town,
      Veneto Region), and on a random sample of population controls selected in each
      CRs area were linked with data on subjects employed in private enterprises that
      have been available in electronic form since 1974 at the National Institute for
      Social Security (INPS). In this way, both for cases and controls, the
      occupational histories of past employment were collected. A population-based case
      control study covering the period 1990-1998 was carried out with the aim of
      estimating occupational cancer risk in the private sector by site and economic
      category in each area. Since one of the major drawbacks of this approach is the
      difficulty in distinguishing true occupational hazards from incidental findings
      derived from multiple comparisons, an extensive research of occupational
      literature was carried out, independently of the study results, to compare our
      results with existing knowledge on occupational risks. RESULTS: Pooled analysis
      of the most recent incidence data based on 36,379 cases and 29,572 controls was
      performed; 34 "statistically significant" associations were found for 11 economic
      categories. Using our literature review, 10 associations were supported by more
      than 5 publishedpapers, 14 by a number of papers between 1 and 5, and 10
      associations had not been previously reported. CONCLUSIONS: This system appears
      suitable for assessing existing occupational cancer risks and can eventually lead
      to detecting occupational hazards in many areas of Italy. The system can also
      provide a list of cases suitable for in-depth search for past occupational
      exposures.

PMID- 15847107
TI  - [Epithelial naso-sinusal cancer incidence and the role of work in 100 cases
      diagnosed in the Province of Brescia (northern Italy), in the period 1978-2002].
AB  - BACKGROUND: Naso-sinusal cancers (NSC) cover a group of rare tumours in Italy for
      which the role of occupational risk has been established. The systematic survey
      of NSC in the province of Brescia made it possible to analyse the jobs of the
      cases occurring in the area. OBJECTIVES: The aims of the research were:
      estimation of epithelial NSC incidence both in the general population and among
      wood and leather workers, description of the frequency and type of occupational
      exposure to substances or manufacturing processes. METHODS: The epithelial type
      cases were obtained from the Naso-sinusal Cancer Register (population-based)
      operating in the Province of Brescia since 1994. Work histories were obtained via
      a standardized questionnaire. RESULTS: The annual incidence ofepithelial NSC (for
      100,000) in the entire population (1,090,000 inhabitants, ISTAT census 1991) from
      1993 to 1997 and from 1998 to 2002 was nearly the same, 0.82 and 0.90 for men,
      0.37 and 0.37 for women, respectively. The nasal cavity was the most affected
      anatomic site (45%) and squamous cell carcinoma was the most frequent histotype
      (44%) among the first 100 cases whose case histories were appropriate; in the
      ethmoidal sinus adenocarcinoma represented 62% of the cases; 25% of all cases
      were exposed to occupational carcinogens (list A) and particularly to wood dust
      (17%), even if only of softwood species (30%), and leather dusts (7%) especially
      in the shoe repair. The average latency period was 47 years (SD 7.4) and 44 years
      (SD 5.6) respectively; 71% of these epithelial NSC cases involved the ethmoid and
      85% were adenocarcinomas. Only 1% of the cases was exposed to chromium and nickel
      and occurred in galvanization processes. Among the exposures to occupational
      risks with limited epidemiological evidence (list B) there was one case exposed
      to formaldehyde and 42 cases occurring in the building, agricultural, metallurgic
      and textile sectors. Thus all the exposures to occupational risks, both certain
      and probable (lists A and B) reached 84% among men and 17% among women.
      Epithelial NSC annual incidence rates (for 100,000) estimated among the wood and
      leather workers for the period 1985-2002 were 13 and 6.5 respectively.
      CONCLUSION: The results confirm the meaning of sentinel event for these tumours
      in occupational health and justify maintaining an active surveillance programme
      for the cases occurring in the area.

PMID- 15847108
TI  - [Guidelines for health surveillance of health care workers exposed to biological
      risks set up by the Italian Society for Occupational Health and Industrial
      Hygiene: application in health facilities of the Regional Health Administration-
      District No. 7, Ancona].
AB  - BACKGROUND: Evidence Based Medicine and the need to achieve better management of
      health budgets call for verification and, if necessary, revision of the criteria
      used in Occupational Health, in order to ensure appropriate measures as regards
      protection of health at the workplace. In December 2003, the Marche Region
      initiated a process of reform of the regional health service, which will be
      completed in two years, and will provide a new regional health organization that
      will improve the quality and appropriateness of health services available to the
      population. The reform also involves the Occupational Health Services responsible
      for prevention activities for 20,000 health care workers employed in regional
      public health facilities. The need was strongly felt to set up a network that
      would meet the health needs of health care workers, by adopting a common language
      among occupational health physicians, by eliminating reported criticism, which is
      due not only to lack of communication between different structures and profiles,
      but also to the different methods of approach, evaluation and management of
      occupational risks. OBJECTIVES AND METHODS: From a historical point of view, the
      health sector has the biggest as regards prevention of biological risk.
      Therefore, with a view to harmonizing actions and approach among occupational
      health physicians in the evaluation of this risk, the publication by the Italian
      Society for Occupational of Health and Industrial Hygiene of Guidelines for
      health surveillance of health care workers exposed to biological risks, produced
      by the working group under the leadership of Prof. Lorenzo Alessio, was
      considered to offer an interesting opportunity to verify the reproducibility of
      methods and the quality of results, as applied to health facilities under the
      Regional Health Administration in Ancona (District No. 7). RESULTS AND
      CONCLUSION: The Guidelines fully confirmed the need to plan activities, starting
      from analysis of epidemiological and occupational data, thus assuring good
      results both in terms of efficacy and efficiency of the health surveillance
      programme used. This method also assures a high level of appropriateness of
      medical measures as regards the "safety" target, at the same time avoiding waste
      and poor management of human and economic resources, which were till now caused
      by differences in methods used in assessment of biological risk.

PMID- 15847109
TI  - [Judicial and medical/legal aspects of the responsibility of workers appointed to
      carry out first aid].
AB  - BACKGROUND: One of the innovations introduced by law 626/94 [the Italian law on
      occupational health and safety of workers] is the obligation of the employer to
      designate workers responsible for first aid. OBJECTIVES: To identify and discuss
      the duties, the role and the medical and legal responsibility of workers
      appointed to carry out first aid measures. METHODS: Analysis of legislation and
      current practice concerning medical and legal responsibility in first aid
      procedures. RESULTS: The worker appointed to carry out first aid measures is, by
      virtue of his appointment, obliged to take action. Therefore, he could commit an
      illegitimate act both by "acting" and by "omitting" to carry out a duty that is
      his responsibility. In the first case the worker could be accused of committing
      an unpremeditated criminal offence when his actions involve negligence,
      imprudence, inexperience or violation of regulations concerning his duties. A
      "serious criminal offence" is committed when the most elementary rules of
      diligence, prudence and skill are violated; the offence is "slight" when
      negligence, imprudence or inexperience are involved in particularly complex
      situations. The reference parameter for inexperience is not a first aid
      volunteer, nor a member of the public, but a worker designated to carry out first
      aid possessing "average" attitudes, training and ability. Briefly, a guilty error
      by the appointed worker consists of the following: i) the professional conduct of
      the operator was clearly wrong, serious and unjustifiable; ii) the operator
      clearly omitted doing his/her duty; iii) the consequence of the error is physical
      personal damage. CONCLUSIONS: The observations made clearly illustrate the
      delicacy of the tasks of the worker appointed to carry out first aid measures.
      Essential elements for minimizing wrong and/or negligent conduct are appropriate
      choice of the designated workers and their adequate training.

PMID- 15847110
TI  - [Occupational Medicine Programme in the university degree on prevention
      techniques in living and working environments].
AB  - This document has been prepared by a working group of University Professors
      belonging to the Italian Society of Occupational Medicine and Industrial Hygiene,
      with the aim of defining the role of this discipline in the university course on
      Prevention Techniques in Working and Living Environments. The course trains
      health professionals to apply risk assessment techniques, preventive measures and
      legislative tools for safety and health in working and living environments, food
      and beverages hygiene, and Public Health. The document describes the organization
      and the structure of the course, general and specific learning objectives,
      occupational medicine teaching and other organization aspects. Also, training of
      non-graduate technicians working for local health authorities is discussed.

PMID- 15847111
TI  - Vaccination against hepatitis B virus in workers of a general hospital in Athens.
AB  - BACKGROUND: Protection against hepatitis B virus infection by vaccination is
      considered to be an important preventive measure for health care workers.
      OBJECTIVES: Investigation of vaccination coverage against hepatitis B virus in
      health care workers of a regional general hospital in Athens and assessment of
      predictive factors possibly associated with the likelihood of vaccination.
      METHODS: In a cross-sectional study, a questionnaire survey was carried out on
      175 health care workers of a regional general hospital in Athens. The
      questionnaire included questions concerning socio-demographic factors, HBV
      vaccination status and reasons for non-vaccination, as well as questions about
      knowledge of routes of transmission and the complications of HBV infection.
      Compliance with preventive practices against HBV infection was also assessed.
      RESULTS: Overall vaccination coverage was 57.1%. Logistic regression analysis
      revealed that occupation and use of gloves were independently associated with the
      likelihood of vaccination against HBV Doctors recorded an odds ratio (OR) for
      vaccination of 4.45 in comparison with nurses/paramedics. Health care workers who
      wore gloves always/most times demonstrated an odds ratio of 2.79 for vaccination
      against HBV in comparison with those who never/rarely used them. CONCLUSIONS: Our
      study illustrates the characteristics of health care workers with lower
      prevalence of vaccination against HBV in a representative sample of these workers
      in a regional general hospital in Athens: nurses/paramedics, those with low level
      of compliance with use of gloves, and those in non surgical departments.
      Educational interventions as part of a vaccination programme and continuing
      education on universal precautions could help increase HBV vaccination coverage
      among health care workers of the hospital under study.

PMID- 15847112
TI  - [Health surveillance of workers exposed to carcinogens].

PMID- 15847113
TI  - [Complaints on diseases caused by exposure to specific risks during military
      service].

PMID- 15847114
TI  - [Experience with surveillance of individuals formerly exposed to asbestos].

PMID- 15847115
TI  - Mitochondrial respiratory chain in brain homogenates: activities in different
      brain areas in patients with Alzheimer's disease.
AB  - BACKGROUND AND AIMS: The potential influence of impaired oxidative metabolism in
      the modulation of manifestations in sporadic Alzheimer's disease (AD) has
      attracted much attention in the last 50 years. Unfortunately, many clinical and
      experimental results aiming at proving this hypothesis are still controversial.
      The aim was to study the enzymatic activities of respiratory chain (RC) complexes
      I through V in three brain areas of a group of patients with definite AD, and to
      compare the results with a group of normal brains. We simultaneously assessed the
      lipid peroxidation of the samples as a measure of free radical damage. METHODS:
      The specific activity of the individual complexes of the RC was measured
      spectrophotometrically, and the loss of cis-parinaric acid fluorescence was used
      to determine the chemical process of lipid peroxidation. RESULTS: We were not
      able to detect differences in any of the analyzed RC enzymatic activities, or in
      the level of lipid peroxidation between patients with AD and controls. Instead,
      differences were found in the number of mitochondria and in the intrinsic
      enzymatic activities of complexes III and IV in various brain areas. CONCLUSIONS:
      Spectrophotometric enzymatic analyses of respiratory complexes in brain
      homogenates do not support the primary contribution of mitochondrial RC
      dysfunction in the pathogenesis of AD.

PMID- 15847116
TI  - Visual assessment of medial temporal atrophy on MR films in Alzheimer's disease:
      comparison with volumetry.
AB  - BACKGROUND AND AIMS: To test the agreement of a visual rating scale of medial
      temporal lobe atrophy (MTA) with linear and volumetric assessments, and to test
      its accuracy in discriminating between Alzheimer's disease (AD) patients and
      controls. METHODS: Participants were 28 patients with AD and 29 healthy controls.
      MTA was evaluated according to Scheltens' five-point scale. Its accuracy in
      distinguishing AD patients from controls was evaluated as a stand-alone measure
      and in association with linear [width of the temporal horn (WTH)] and volumetric
      [hippocampal volume (HV)] measures. RESULTS: The agreement of this visual rating
      scale with the other MTA measures was statistically significant (vs WTH and vs
      HV, p for trend < 0.00005). The visual rating scale showed a good accuracy in
      distinguishing AD patients from controls [area under the curve (AUC) 0.89, 95%
      confidence interval (CI) 0.79-0.98]. Although the accuracy of the visual rating
      scale improved in association with linear WTH (AUC 0.91, 95% CI 0.82-0.99) and in
      association with HV (AUC 0.93, 95% CI 0.86-1.00), the improvement was not
      significant. CONCLUSIONS: The visual rating scale of MTA, easily applicable in
      clinical practice, shows good agreement with more demanding quantitative methods,
      and can discriminate AD patients from controls with good accuracy.

PMID- 15847117
TI  - Prescription and choice of diagnostic imaging by physician specialty in
      Alzheimer's Centers (Unita di Valutazione Alzheimer - UVA) in Northern Italy.
AB  - BACKGROUND AND AIMS: Physician's specialty has been shown to have an effect on
      health outcomes and financial expenditure in a number of conditions. This is
      particularly true in the differential diagnosis of cognitive deterioration, in
      which technological procedures are needed. The aim of this study is to assess the
      effect of physician specialty on the prescription of diagnostic imaging (CT and
      MR) in patients with cognitive impairment, referred to Alzheimer Evaluation Units
      (Unita di Valutazione Alzheimer) in Northern Italy. METHODS: An ad-hoc
      questionnaire was sent to UVA referents in northern Italy (Lombardy, Piedmont,
      Trentino, Emilia-Romagna and Veneto), requesting information on the frequency of
      prescriptions for CT and MR and reasons for the choice, on a 0 to 7 scale.
      RESULTS: The physician-in-charge was a neurologist in 22 and a geriatrician in 22
      Alzheimer's centers. Intensive use of CT was similar in neurologists and
      geriatricians (64 vs 68%), whereas intensive use of MR was more frequent in
      neurologists (41 vs 10%; p = 0.03). Overall, organizational factors (availability
      of the scanner on-site and waiting list for imaging, mean weight = 1.6 +/- 1.4)
      were as important as patient-related factors (age, severity of cognitive
      impairment, and clinical suspicion of cerebrovascular disease, mean weight 1.7 +/
      1.4; p = 0.84). Sixty-five percent of neurologists based their choices between
      CT and MR on patient-related and 35% on organizational factors, whereas the
      opposite proportion was found for geriatricians (29 vs 71%, p = 0.04).
      CONCLUSIONS: The high weight of organizational factors on the prescription of
      diagnostic imaging is not consistent with an evidence-based diagnostic system.

PMID- 15847118
TI  - Association of cognitive status with functional limitation and disability in
      older adults.
AB  - BACKGROUND AND AIMS: Although cognitive status is known to be associated with
      physical function in older people, the role it plays in the disability process is
      not well established. This study aimed at determining whether cognitive ability
      predicts functional limitations, as well as disability, and whether it is
      associated with the rate of change in physical functions. METHODS: A community
      based longitudinal study was conducted, involving 977 older persons aged 65 and
      older living in an urban community. Physical functions were assessed by tests
      scoring functional limitations (upper and lower body) and disability (activities
      of daily living). Cognitive function was evaluated using the Mini-Mental State
      Examination. Linear regression analyses with generalized estimating equations
      modeled the two physical function scores separately, as functions of cognitive
      status and time, in a one-year follow-up, controlling for sociodemographic and
      health-related characteristics. RESULTS: Cognitive status independently predicted
      functional limitations as well as disability in older people. In addition, the
      strength of the association of cognitive status with physical functions increased
      over time, as revealed by the significant interaction between cognitive ability
      and time. Cognitive status influenced the rate of change in disability scores,
      more among women and in those aged 75 or older. The relationship was unaffected
      by baseline physical functional status, but was significant only among those with
      no cognitive impairment at baseline. CONCLUSIONS: Cognitive status appears to be
      a useful indicator of the disablement process in older people. It may play an
      important role in the development of disability, implying that strategies for
      early intervention to prevent the progression of disability may need to take
      cognitive functions into account. The increasing strength of the relationship
      between cognitive and physical functions over time further attests to its value
      in monitoring functional change.

PMID- 15847119
TI  - Italian Project on Epidemiology of Alzheimer's disease (I.PR.E.A.): study design
      and methodology of cross-sectional survey.
AB  - BACKGROUND AND AIMS: The purpose of this paper is to describe the design and
      diagnostic procedures of the multicenter community-based prospective Italian
      Project on the Epidemiology of Alzheimer's disease (I.PR.E.A.). The study is
      aimed at estimating the prevalence and incidence of Alzheimer's disease (AD) in
      the preclinical phase, examining the natural history of cognitive decline without
      dementia (mainly AD) in the Italian population, and identifying risk factors or
      health determinants related or associated with various health outcomes. METHODS:
      Both cross-sectional and longitudinal phases will be performed in 4800 elderly
      subjects aged 65-84 years. The sample will be selected from the registries of 12
      Italian rural and urban municipalities, with an interval of one year between
      examinations. The study population will undergo several screening examinations,
      including personal and informant interviews by means of a structured ad hoc
      questionnaire, physical and neurological examination, laboratory tests, genetic
      markers and a neuropsychological battery. Neuroimaging screening will also be
      carried out in a subgroup of subjects positive for cognitive impairment without
      dementia. The longitudinal phase will include all subjects who, during the cross
      sectional survey, are identified as affected by cognitive impairment without
      dementia, and will aim at assessing the incidence and natural history of
      cognitive impairment without dementia and the degree of disease progression from
      the earliest stage. This is the first systematic prospective study on the
      preclinical phase of AD in Italy.

PMID- 15847120
TI  - Functional status and satisfaction with community participation in persons with
      stroke following medical rehabilitation.
AB  - BACKGROUND AND AIMS: Researchers and policy-makers have recognized that quality
      of life assessments are essential to better understand the benefits of
      rehabilitation intervention. The purpose of the study was to examine associations
      between functional status and satisfaction with community participation for
      persons with stroke at 80-180 days after discharge from medical rehabilitation.
      METHODS: The study was retrospective, using data from the Information Technology
      (IT) Health-Track database for patients discharged from medical rehabilitation
      facilities in 2001/2002. The study population included 1870 persons with stroke
      aged 40 or older who had complete information at admission and follow-up (mean
      age at admission 68.3 yr, SD 14.5). The sample was 49.3% female and 72.6% were
      non-Hispanic white. RESULTS: Results showed a significant positive association
      between change in functional status (admission to follow-up) and satisfaction
      with community participation. Positive change ratings in functional status were
      associated with increased satisfaction with community participation (b = 0.02, SE
      = 0.001, p = 0.0001), after adjustment for age, gender, marital status,
      race/ethnicity, insurance source and functional status score at admission.
      Similarly, positive associations were observed for changes in motor and cognitive
      subscale ratings and satisfaction with community participation. The strongest
      association among six functional status domains and satisfaction with community
      participation was for communication (beta = 0.60) and social cognition (beta =
      0.58). CONCLUSIONS: This study showed a statistically significant association
      between a modifiable factor (functional status) and a quality of life indicator
      (satisfaction with community participation). Results add to emerging literature
      on patient-centered outcomes and extend measures of recovery beyond functional
      status to include consumer satisfaction with a community outcome.

PMID- 15847121
TI  - Deep venous thrombosis in elderly hospitalized patients: prevalence and clinical
      features.
AB  - BACKGROUND AND AIMS: It is not known whether old age influences the clinical
      outcome of deep venous thrombosis (DVT) in patients admitted to acute internal
      medicine wards. This study aimed at evaluating the effect of age on the
      prevalence and clinical features of DVT in patients admitted to acute medical
      wards in a general hospital. METHODS: All patients with a discharge diagnosis of
      DVT during a 4-year period from 1999 to 2002 were identified. Age, gender, main
      and secondary diagnoses, diagnostic procedures, and length of stay (LOS) were
      recorded. The severity index was calculated by the All Patients Refined
      Diagnostic Related Groups (APR-DRG) grouper and graded as mild, moderate, severe
      or extreme. RESULTS: 310 patients with DVT were identified: 163 males and 147
      females. Mean age was 62 +/- 16 years, with a range of 17-94 years. 174 patients
      (56%) were over 65 years old (mean age = 74.2 +/- 6.2, range 65-94 years) and 136
      (44%) were young or adults (mean age = 48.3 +/- 12.9, range 17-64 years). The
      overall prevalence of DVT was 1.51%, with no differences between males and
      females (1.46 vs 1.56%, p = NS). In elderly subjects, the prevalence of DVT was
      significantly higher than in young or adult patients (1.7 vs 1.2%, p = 0.005) and
      was more frequently associated with pulmonary embolism (12 vs 7%, p < 0.05) and
      less with neoplasms (10 vs 30%, p < 0.05) than in young patients. Diagnostic
      procedures performed during the hospital stay were similar for elderly and young
      patients whereas LOS was significantly longer in elderly than young patients
      (14.1 +/-11.5 vs 11.7 +/- 9 days, p < 0.05). The APR-DRG severity index was
      significantly higher in elderly than in young patients (p < 0.05). CONCLUSIONS:
      Elderly patients with DVT reveal higher prevalence and have different clinical
      features than young or adult patients. Further studies are needed to better
      evaluate predisposing conditions and clinical outcomes of DVT in old age.

PMID- 15847122
TI  - The Caregiver Burden Inventory in evaluating the burden of caregivers of elderly
      demented patients: results from a multicenter study.
AB  - BACKGROUND AND AIMS: The burden perceived by caregivers of patients with dementia
      is a fundamental prognostic aspect in the history of the disease. The aim of this
      study was to demonstrate the internal consistency of the Caregiver Burden
      Inventory (CBI), a scale used to quantify burdens in different aspects of a
      caregiver's life, and the influence of patients' and caregivers' characteristics
      on its different dimensions. METHODS: In this cross-sectional study, 419 demented
      patients and their caregivers were evaluated in 16 geriatric centers in Italy.
      Cognitive status and behavioral disturbances were assessed by the Mini Mental
      State Examination (MMSE) and Neuropsychiatric Inventory (NPI), respectively.
      Activities of Daily Living (ADL) and Instrumental Activities of Daily Living
      (IADL) were also evaluated. Comorbidity was assessed by the Cumulative Illness
      Rating Scale (CIRS). The severity of dementia was evaluated by the Clinical
      Dementia Rating (CDR) score. Caregiver distress due to the behavioral problems of
      the patient was assessed by the Neuropsychiatric Inventory-Distress, a subscale
      of the NPI which evaluates stress caused by each behavioral disturbance of the
      patient, and by the Brief Symptom Inventory which evaluates anxiety and
      depression. Burden was evaluated by the CBI. RESULTS: The CBI showed very high
      internal consistency (Cronbach's alpha value > 0.80). Factor analysis showed that
      the items clustered into four dimensions, and not five as originally proposed.
      Multiple regression analysis revealed that patients' behavioral disturbances and
      disability were the major predictors of the time-dependent burden; the
      psychophysical burden was explained mainly by caregiver anxiety and depression.
      CONCLUSIONS: The CBI proved to be an effective multidimensional tool for
      evaluating the impact of burden on many aspects of caregivers' lives.

PMID- 15847123
TI  - Results of a multi-level therapeutic approach for Alzheimer's disease subjects in
      the "real world" (CRONOS project): a 36-week follow-up study.
AB  - BACKGROUND AND AIMS: Recently, the Italian Ministry of Health started a national
      project (CRONOS project), aiming at assessing how a multi-level therapeutic
      approach--including 2-year free-of-charge treatment with cholinesterase
      inhibitors (ChE-I), pharmacologic and non-pharmacologic management of behavioral
      disorders, periodic multi-dimensional assessment, and informal caregivers'
      counseling-performs in subjects with mild-to-moderate Alzheimer's disease (AD).
      Five hundred and three Alzheimer Evaluation Units (AEUs) were instituted for this
      purpose all over Italy. In this paper we present the results of this approach in
      a large population of AD subjects followed for 36 weeks by 14 AEUs in Eastern
      Lombardy, Italy. METHODS: The project lasted for two years (September 2000
      September 2002). Subjects eligible for the CRONOS project had a diagnosis of
      probable AD, a Mini Mental State Examination (MMSE) score at baseline ranging
      from 10 to 26, and onset of cognitive disorders between 40 and 90 years of age.
      Periodic clinical and multi-dimensional assessments, including MMSE, Activities
      of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) were
      made at 12 and 36 weeks; ChE-I doses, psychotropic and antidepressant drugs were
      also re-assessed at all clinical examinations. Caregivers were instructed about
      dementia and drug-related problems. RESULTS: Of the 808 subjects who completed
      the 36-week follow-up, 441 were naives (i.e., never previously treated with ChE-I
      drugs) and 367 non-naives. At 12 weeks, both naives (mean variation from baseline
      = 0.8 points) and non-naives (mean variation from baseline = 0.5 points) improved
      their MMSE scores, while at 36 weeks only naives improved (mean variation from
      baseline = 0.1) and non-naives decreased (mean variation from baseline = -1.2).
      The IADL and ADL scores progressively and mildly declined from baseline to the
      36th week (ADL, mean variation from baseline = -0.5 for naives, -0.3 for non
      naives; IADL = -0.7 for naives, mean variation from baseline = -0.4). However,
      when the MMSE, ADL and IADL variations were controlled for age, sex and
      education, no significant time effect was found (MMSE, Wilks' lambda p = 0.34;
      ADL, Wilks' lambda p = 0.25; IADL, Wilks' lambda p = 0.3, respectively). These
      patterns were apparently unrelated to ChE-I doses. Neuroleptic use doubled in
      naives and antidepressants increased in both groups. CONCLUSIONS: This multi
      level therapeutic approach seems to slow down progression in cognitive and
      functional performance, in both naive and non-naive subjects. The possibility of
      recurrent examinations by specialized physicians, accurate, lose management of
      psychotropic drugs, and informal counseling to caregivers probably aid in
      achieving such results in a "real world" population of AD elderly subjects living
      at home. Future studies are needed to assess whether a multi-level therapeutic
      approach including higher ChE-I dose may perform better in these subjects.

PMID- 15847124
TI  - Ruffled hair and fever in an old woman with Alzheimer's disease.
AB  - In patients with dementia, the clinical presentation of unrelated medical
      conditions may be concealed or atypical, and symptoms difficult to interpret, or
      confounded by existing cognitive deterioration or by medications. These
      difficulties pose an extraordinary challenge to clinicians, and may contribute to
      the disturbing evidence of inadequate assessment and treatment of medical
      conditions in patients with dementia. Here, we report the case of an 82-year old
      woman diagnosed with Alzheimer's disease, whose MMSE score started to deteriorate
      rapidly after six years of steady decline as a result of a temporal arteritis.
      Temporal arteritis, a diagnosis which is often made several months after the
      onset of symptoms even in the general population, can be difficult to identify in
      patients with pre-existing dementia.

PMID- 15847125
TI  - Primary hyperparathyroidism and neuropsychiatric alterations in a nonagenarian
      woman.
AB  - Whether elderly patients with asymptomatic or minimally symptomatic primary
      hyperparathyroidism (PHPT) should be treated or not is still under debate.
      Several literature reports have shown improvements in terms of bone density and
      physical and mental well-being after surgical resolution of PHPT. Here, we
      present the case of a 93-year-old hypertensive woman, who had suffered for one
      year from cognitive impairment, accompanied during the last month by behavioral
      alterations (and polyuria and polydipsia), which resulted in sopor leading to
      hospitalization. A CT brain scan evidenced cortical atrophy and cerebrovascular
      disease, and biochemical analyses were remarkable for hypercalcemia (11.4-12.6
      mg/dL, corrected for albumin levels) associated with increased parathormone
      levels (95.4-100.6 pg/mL). A diagnosis of PHPT was established. Densitometry
      evaluation of radius showed osteopenia. Withdrawal of psycho-therapy drugs and
      thiazidic, together with i.v. saline hydration and loop diuretics, significantly
      improved the patient's mental state and resolved behavioral alterations. As the
      patient and her relatives refused the surgical option, and the clinical situation
      improved after medical normalization of calcium levels, PHPT was managed
      conservatively, and calcium levels were maintained within the normal range
      through i.v. administration of zoledronate at 8-week intervals. Our case
      highlights the importance of considering hypercalcemia as the cause of onset of
      behavioral alterations and worsening of mental condition in elderly patients with
      cognitive decline. Therapy with bisphosphonates in patients with PHPT who are
      unfit for or refuse surgery seems advisable, but needs further study.

PMID- 15847126
TI  - Molecular genetics: is it making an impact in the management of inherited
      arrhythmogenic syndromes?

PMID- 15847127
TI  - Cardiac surgery in adults with congenital heart disease: an emerging challenge.

PMID- 15847128
TI  - Electrocardiographic changes resulting from peripheral edema: theoretical
      considerations and clinical implications.

PMID- 15847129
TI  - Anti-cytokine therapies in chronic heart failure: is this concept still alive?

PMID- 15847130
TI  - Magnetic resonance imaging in the detection of myocardial viability: the role of
      delayed contrast hyperenhancement.

PMID- 15847131
TI  - Medium-term results from the clinical and angiographic follow-up of patients
      after angioplasty and implantation of sirolimus-eluting stents.
AB  - INTRODUCTION: The aim of this study was to evaluate the medium-term clinical and
      angiographic results, as well as the occurrence and treatment of restenosis,
      following the implantation of sirolimus-eluting stents (SES) in patients
      undergoing coronary angioplasty. METHODS: All patients who have an SES implanted
      in our department are entered into a database, with a view to evaluating the use
      of such stents in everyday clinical practice. This study included patients who
      consented to repeat angiography 8+/-2.4 months after stent implantation. The
      study population consisted of 91 patients (63 men, mean age 58+/-8.1 years) with
      116 stenoses in all. This represented 17.4% of all patients who had an SES
      implanted during the study period. All the angiographic examinations were
      analysed independently using quantitative coronary analysis in order to determine
      the relationship between clinical and angiographic data and restenosis and late
      lumen loss. RESULTS: The mean vessel diameter was 2.5+/-0.48 mm and the mean
      lesion length was 12.61+/-1.54 mm. The late lumen loss was 0.04+/-0.49 mm.
      Restenosis was seen in 10 patients (12 vessels), of whom 4 were diabetics. The
      restenosis was in-stent in 7 vessels, in-segment in 5, and was localised (length
      of restenosis <10 mm) in all patients. After repeat angioplasty and SES
      implantation all the patients with restenosis remained free of symptoms 8+/-1.5
      months later. Diabetes mellitus was the only factor to be correlated with
      restenosis. CONCLUSIONS: Restenosis following implantation of SES is mainly
      localised and occurs with about the same frequency within and outside the stent.
      The incidence of major cardiac events and restenosis following SES implantation
      is low. However, their long term efficacy in everyday clinical practice must be
      proved in large randomised studies in order to confirm the results presented
      here.

PMID- 15847132
TI  - The use of drug-eluting stents in everyday clinical practice: can the results of
      randomised trials be achieved in the "real world"?

PMID- 15847133
TI  - Successful surgical correction of congenital heart disease in adults: seven
      years' experience.
AB  - INTRODUCTION: The long term consequences of untreated or residual/recurrent
      lesions pose unique challenges in the growing population of adults with
      congenital heart disease (CHD). This study summarizes the results of the surgical
      treatment of these patients. METHODS: From October 1997 to October 2004, 289
      patients with CHD, aged 18-72 (35+/-13.6) years, 143 men and 146 women, presented
      for surgery to our unit. Thirty eight patients (13.15%) had 1 to 3 prior surgical
      procedures. Although 137 patients (47%) were asymptomatic (NYHA I), 117 (40.5%)
      had mild (NYHA II), 34 (11.7%) moderate (NYHA III) and 1 (0.3%) severe (NYHA IV)
      symptoms. Thirty four patients had an established arrhythmia, requiring treatment
      in 25 (8.6%). Chromosomal anomalies were identified in 10 (3.4%) and diagnostic
      catheterization was required in 178 (61.5%) patients. All patients underwent
      complete surgical correction and in 275 (95%) of them this was performed with
      cardiopulmonary bypass of 107+/-74 min mean duration. RESULTS: There was 1 early
      death (0.34%) due to embolic stroke related to atrial fibrillation (AF).
      Complications occurred in 50 patients (17%) and included re-operation for
      bleeding (5), stroke (3), pneumothorax (12), AF (22), complete heart block
      requiring permanent pacemaker implantation (2), wound dehiscence (1), pericardial
      (7) or pleural (3) effusion requiring drainage and peripheral neuropathy (1).
      Median intensive care unit and hospital stay was 1 (range 1-10) and 8 (range 5
      42) days respectively. Two late deaths (0.7%) occurred in patients with AF and
      pulmonary hypertension. At mean follow-up of 45+/-24 (range 1-82) months all
      other patients are well with resolution or significant improvement in their
      symptoms. CONCLUSION: Despite the long term deleterious effects of CHD in adult
      patients, surgical correction can be achieved with low mortality and acceptable
      morbidity. All deaths and most significant complications are related to
      arrhythmias.

PMID- 15847134
TI  - Congenital heart disease in adult patients.

PMID- 15847135
TI  - Prognosis and management of diabetic patients with acute coronary syndrome.

PMID- 15847136
TI  - Pulmonary valve replacement with aortic homograft.

PMID- 15847137
TI  - Idiopathic right ventricular outflow tract tachycardia induced during acute
      episode of atrial fibrillation.
AB  - Tachycardia-induced tachycardia is a rare condition. We report a case in which an
      episode of paroxysmal atrial fibrillation led to right ventricular outflow tract
      tachycardia. We also analyse all potential mechanisms that might contribute to
      the coexistence of these two different arrhythmias in the same patient.

PMID- 15847138
TI  - Electrocardiographic picture of acute anterior infarction due to proximal
      obstruction of the right coronary artery.
AB  - Proximal occlusion of the right coronary artery may, in certain circumstances,
      cause elevation on the anterior wall leads. This can occur more easily when the
      size of the lesion in the inferior wall is small compared to that in the right
      ventricle. The size distribution of the elevations in the above leads is
      different from that seen when the anterior descending branch is occluded. More
      rarely, isolated right ventricular infarctions on a substrate of a non-dominant
      right coronary artery can cause elevations exclusively on the anterior wall
      leads, with no ECG changes in the inferior leads. We describe the case of an
      acute myocardial infarction with isolated elevations on the anterior wall leads,
      with no accompanying changes in the inferior leads, where the lesion responsible
      was acute proximal occlusion of the right coronary artery.

PMID- 15847139
TI  - Ventricular special defect in the elderly: an uncommon clinical entity.
AB  - Ventricular septal defect (VSD) is the most frequent congenital heart disease in
      adults, with equal distribution in both sexes, and has an incidence of about 20%
      in children. In adults congenital VSDs represent about 10% of all cases and the
      mortality at age 60 is around 75%. For elderly patients >80 years old only one
      living case has been reported previously. Here we describe an 86-year-old
      patient, totally asymptomatic, with a muscular type of VSD that showed
      interesting, canal-like echocardiographic images.

PMID- 15847140
TI  - Meritocracy, motivation and centres of excellence: what Greek cardiology needs.

PMID- 15847141
TI  - Greece: one of the thirty top-performing countries in all scientific fields?

PMID- 15847142
TI  - [Transcendental historical events of Mexican gynecology and obstetrics].

PMID- 15847143
TI  - [Dietary intake and nutritional status of pregnant women enrolled in the Mexican
      Institute of Social Security, living in a peri-urban area of Mexico City].
AB  - OBJECTIVE: To identify the combinations and type of foods consumed, energy
      intake, nutrients and nutritional status in pregnant women. METHODOLOGY: One
      hundred and twelve primiparous women, who attended prenatal care at a primary
      care clinic located in the metropolitan area of Mexico City were included.
      Information about dietary intake was collected through a 24-hour recall
      questionnaire. Energy intake, nutritional intake and appropriateness of
      nutritional intake were assessed. Nutritional status was evaluated through
      expected weight for height according to gestational age. RESULTS: Average age was
      of 22 +/- 4.1 years and mean duration of pregnancy of 28 weeks. There was an
      adequate intake of energy, thiamine, riboflavin and calcium; whereas a low intake
      of iron, folate and zinc was observed, 47% of pregnant women were overweighted.
      CONCLUSIONS: A poor variety in dietary intake was identified, as well as
      inadequacies in mineral and vitamin intake; additionally, an inadequate
      nutritional status was found in more than 50% of pregnant women.

PMID- 15847144
TI  - [Occurrence of preterm and term low birth weight deliveries and presence of the
      Sydney crease].
AB  - OBJECTIVE: To determine whether simian and Sydney creases are associated to
      preterm delivery or to term low birth weight. PATIENTS AND METHODS: We performed
      a cross-sectional study of 490 live newborns without apparent malformations from
      the Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Guadalajara, Mexico).
      Patients were categorized in three groups: group I: 175 infants with preterm
      delivery; group II: 140 term low birth weight infants; group III: 175 at term
      newborns with adequate weight for gestational age. On all groups, perinatal
      history was registered and palm creases were studied by direct inspection and
      classified as normal, simian crease (single palmar flexion crease) or Sydney
      crease (continuation of the proximal palmar crease until the ulnar border of the
      palm). We used the odds ratio as an association measurement, with 95% confidence
      intervals. RESULTS: The simian crease frequency did not show significant
      differences between groups. Sydney crease frequencies on groups I, II and lll
      were 29.7, 34.2 and 18.2%, respectively (p = 0.0037). Sydney crease presence was
      associated with near to two-fold frequency to preterm birth (OR: 1.89, 95% CI:
      1.11-3.23) and more than double with low birth weight (OR: 2.33, 95% Cl: 1.07
      5.23). CONCLUSIONS: Sydney crease was associated with occurrence of the preterm
      and term low birth weight deliveries.

PMID- 15847145
TI  - [Intrafollicular levels of sexual steroids and their relation with the
      antioxidant enzymes on the oocyte quality in an in vitro fertilization program].
AB  - OBJECTIVE: To establish a correlation between intrafollicular superoxide
      dismutase enzyme concentrations, activity with oestradiol levels, and the effects
      on oocyte quality and maturity. STUDY: Prospective, descriptive and
      observational. MATERIAL AND METHODS: Forty-one patients underwent IVF-ET program.
      The ovarian stimulation protocol was made with recombinant FSH and GnRH
      antagonists. All follicles were aspirated one by one, and the follicular fluid
      was stored at a -20 degrees C room temperature. We retrieved 120 follicular
      fluids and performed the measurement of oestradiol and superoxide dismutase
      enzyme on each follicular fluid and its correlation with fertilization and
      cleavage rates. Statistical analysis was carried out with ANOVA, t Student, chi2
      and P Pearson tests. RESULTS: Patients' mean age was of 33.74 +/- 5.04 years, the
      mean of enzyme activity was of 76.89%, and the mean concentration of superoxide
      dismutase enzyme was of 68.71 UI/L. According to oocyte quality or maturity, no
      statistical differences were observed when comparing oestradiol levels with
      superoxide dismutase enzyme concentrations. But when we analized both variables,
      we observed a positive correlation in metaphase 2 oocytes (p = 0.236). When we
      correlated the superoxide dismutase enzyme activity with oestradiol
      concentrations in relation to oocyte quality, a positive correlation in good
      quality oocytes was observed too (p = 0.218). We perceived a strong correlation
      between SOD concentrations and oestradiol intrafollicular measurements in good
      quality oocytes. COMMENTS: Oocyte maturity and development are conditionated by a
      close relationship between SOD and intrafollicular oestradiol.

PMID- 15847146
TI  - [Usefulness of luteinizant hormone levels to determine the oocyte quality].
AB  - OBJECTIVE: To evaluate the luteinizing hormone serum preovulatory levels and
      correlate them with the embryo number and quality, and with the fertilization and
      clavage rates. STUDY: Prospective, descriptive and observational. MATERIAL AND
      METHODS: We included 286 patients that underwent to IVF-ET program, we excluded
      patients with no mesurement of LH preovulatory levels, or patients that in the
      oocyte retrieval we do not found oocytes. The protocols for pituitary inhibition
      were: stop Lupron, long luteal phase and GnRH antagonist, the ovarian stimulation
      was realized with recombinant FSH. The studied variables were: LH preovulatory
      levels, number and quality of oocytes, fertilization and clevage rates and embryo
      quality. Statistical analysis was done with p Pearson and ANOVA tests. RESULTS:
      The mean age for patients was 34 +/- 3.96 years, the principal factor of
      infertility was tubal and pelvis pathology. The mean LH preovulatory levels were
      2.19 +/- 1.83 UI/L by patient, we observed a negative correlation between LH
      levels and number of oocytes retrieved (p = -0.157, IC 99%), and the correlation
      between LH levels and number of metaphase 2 oocyte was negative too (p = 0.113,
      IC 95%). We observed greater levels of LH (3.15 UI/L) in the degenerated oocytes
      during oocyte retrieval. We did not found a statistical correlation between
      fertilization and cleavage rates with LH levels. LH preovulatory levels of 0.85
      UI/L could predict good quality oocytes with a sensitivity of 72% and specificity
      of 25%. CONCLUSIONS: Normogonadotrophic patients without deep suppression of
      gonadotrophins by the use of GnRH analogues, high LH preovulatory levels
      correlates with a less number of oocytes, and with degenerated oocytes.
      Preovulatory LH levels of 0.85 UI/L could predict good quality oocytes.

PMID- 15847147
TI  - [Prevalence of sexually transmitted infections and associated risk factors among
      female commercial sex workers in Cuautla, Morelos].
AB  - OBJECTIVE: To determine the prevalence of sexually transmitted infections (STI)
      among female commercial sex workers in Cuautla, Morelos, Mexico. MATERIAL AND
      METHODS: A cross-sectional survey was conducted in 1998, in the red-light
      district of Cuautla, Morelos, Mexico. It included 100 female commercial sex
      workers who labored permanently in bars and night clubs. Data were collected
      using two questionnaires, one on socio-demographic characteristics, and the other
      on commercial sex, risk perception, and knowledge on preventive measures and
      contagion of sexually transmitted diseases/AIDS. Blood and cervicovaginal
      specimens were also collected to assess the prevalence of sexually transmitted
      and reproductive system infections (RSI). Outcome variables were STI (syphilis
      and chlamydiasis) and RSI (vaginosis and candidiasis). RESULTS: Sexually
      transmitted prevalence was of 11%, reproductive system infections prevalence was
      of 39%. When candidiasis was included in the sexually transmitted infections
      group, prevalence was of 31%. The main factors associated with sexually
      transmitted infections were: who instructed on condom use, time having
      intercourse with partner, and years of commercial sex work. Factors related to
      reproductive system infections were: illiteracy, use of condom with partner, who
      instructed on condom use, and years of commercial sex work. Multivariate analysis
      showed an increased likelihood of acquiring a sexually transmitted infection
      and/or reproductive system infection with illiteracy, instruction on condom use
      by a person other than a healthcare worker, and lack of condom use. CONCLUSIONS:
      Regular use of condoms during intercourse is the most important preventive
      measure to avoid and control STI and RSI. Study findings pinpoint spatial and
      temporal factors that contribute to infection. Intervention measures directed at
      these factors should strengthen preventive and educational programs to improve
      medical care for these infections.

PMID- 15847148
TI  - [Differences and similarities of preeclampsia and gestational hypertension].
AB  - Current criteria regarding hypertension in pregnancy consider two distinct types:
      gestational hypertension (pure type) and preeclampsia-eclampsia syndrome, the
      latter with albuminuria as a mandatory clinical fact. However, reports of lasts
      years show that a 15 to 46% of cases classified as pure type gestational
      hypertension evolve to a preeclamptic state, underlying the possibility that both
      clinical conditions represent diferent stages of the same disease. On the other
      hand, albuminuria may not be present in severe cases of pregnancy-related
      hypertensive disorders such as HELLP syndrome or eclampsia. It follows that if
      albuminuria is not necessary to establish the most severe forms of the disease,
      must the non-albuminuric hypertensive-type still be considered as a diferent
      diagnosis? This report reviews the medical literature on the subject, stressing
      similarities and diferences of both conditions in order to reflect about the need
      to change the classification concepts pregnancy-related hypertensive entities.

PMID- 15847149
TI  - [Uterine leiomyosarcoma. A report of a case].
AB  - A 33 years old male patient was admitted at the Ginecology/Obstetric emergency
      room with acute pain abdomen. The patient underwent an exploratory laparotomy
      where it was found 1,400 cc of blood in the peritoneal cavity. It was also found
      a 10 cm diameter tumor on the right lateral uterus side involving the uterine
      tube, the ovary and the ipsilateral parametrium. In the omentum there were found
      two 3 cm diameter tumors like the one found in the uterus. The bleeding was under
      control so it was made a hysterectomy, bilateral salpingooophorectomy and
      omentectomy. Histopathologic diagnosis was reported two weeks after. The final
      diagnosis was serosa infiltration, uterine leiomyosarcoma and implant on
      peritoneum.

PMID- 15847150
TI  - [Medium forceps technique. 1949. Ginecologia y Obstetricia de Mexico
      1949;IV(Nums.18-19):124-5 ].

PMID- 15847151
TI  - [Preliminary research on bacterial diversity of Parece Vela Basin, Pacific Ocean
      by culture-independent method].
AB  - The environmental DNA was directly extracted from the sediment in Parece Vela
      Basin, Pacific Ocean, at a depth of 5010 m. Bacterial 16S rRNA gene library of 32
      clones was generated using bacterial universal primers and 16S rDNA sequences
      were analyzed phylogenetically. 17 phylotypes were obtained. The library was
      dominated by gamma-Proteobacteria, alpha-Proteobacteria and marine uncultured
      bacteria. Sixty-two percent of the cloned sequences was highly related to the
      known bacteria in the genus Halomonas, Alcanivorax, Pseudomonas, Acinetobacter,
      Pseudoalteromonas (> 96% sequence similarity), while some of the cloned sequences
      showed less affiliation with known taxa (< 94% sequence similarity) and may
      represent novel taxa.

PMID- 15847152
TI  - [Screening and identification of a strain for hydroxylation of nicotinic acid].
AB  - Strain screening was conducted on a large scale in order to develop a
      biotransforming process for 6-hydroxynicotinic acid production. A strain named as
      NA-1 was isolated from soil which could transform nicotinic acid into a new
      product showed by HPLC. The new product was identified as 6-hydroxynicotinic acid
      by MS and 1H-NMR. The morphology, physiological and biochemical characteristics
      of strain NA-1 were studied and showed that characteristics of strain NA-1 were
      essentially consistent with Pseudomonas putida. The analysis of 16S rDNA sequence
      from strain NA-1 suggested that strain NA-1 was clustered together with P. putida
      in phylogenetic tree and the sequence identity between stain NA-1 and Pseudomonas
      putida was 99%. So strain NA-1 was identified to P. putida.

PMID- 15847153
TI  - [Preliminary study on autoregulation of samR involved in development and
      differentiation of Streptomyces ansochromogenes].
AB  - The previous result showed that samR plays an important role in the development
      progress of Streptomyces ansochromogenes. It was reported that the
      differentiation progress of S. ansochromogenes was accelerated by a recombinant
      plasmid containing an extra copy of samR gene. However, the differentiation
      progress of S. ansochromogenes was not further accelerated by a multicopy plasmid
      containing samR gene. Electrophoresis mobility shift assay (EMSA) demonstrated
      that SamR binds to its own promoter region specifically. All these results hint
      that samR is an autoregulatory gene in Streptomyces ansochromogenes.

PMID- 15847154
TI  - [Study on genes involved in biosynthesis and regulation of pigments in
      Pseudomonas aeruginosa].
AB  - Mu transposition recombination technique was firstly used as a mutagenesis tool
      to explore a cluster of genes involved in biosynthesis and regulation of pigments
      in P. aeruginosa. Eight pigment mutants were screened and identified. Gene
      cloning and sequencing of the region flanking the insertion revealed that the
      genes hmgA, ptsP, sucC, phzS, phzF1 were disrupted with mini-Mu respectively.
      Among them, gene hmgA is involved in the degradation of tyrosine, others affect
      the metabolism of pyocyanin which is the most important pigment of P. aeruginosa.
      Both gene phzS and gene phzF1 have been experimentally demonstrated to
      participate in pyocyanin synthesis. Gene ptsP belongs to a phosphotransferase
      system and gene sucC encodes succinyl-CoA synthetase beta chain. This is the
      first report that gene ptsP and sucC may be involved in the regulation of the
      biosynthesis of pyocyanin.

PMID- 15847155
TI  - [Study on AHL-like quorum signals in Mesorhizobium huakuii].
AB  - Quorum sensing is a mechanism used by single-cell bacteria to monitor their
      population density and control a variety of physiological functions in a cell
      density-dependent manner. An ultrasensitive quorum signal acyl-homoserine lactone
      (AHL) detecting Agrobacterium tumefaciens strain, which strongly overproduces
      quorum-sensing regulator TraR and was proved to be able to detect AHLs at nano
      molar concentration, was used to detect the production of AHLs in three
      Mesorhizobium huakuii strains. We showed that AHLs were produced in these strains
      with some variations. We also found that elevating of medium pH during cell
      growth greatly affected the stability of AHL signals. This study paved the way of
      further studying the relationship between quorum sensing and symbiotic nitrogen
      fixation of the M. huakuii strains.

PMID- 15847156
TI  - [Construction of fused osmoregulation proBA gene from a salt-tolerant mutant of
      Bacillus subtilis and its influence on the osmotolerance of Escherichia coli].
AB  - The osmoregulation proB and proA genes from Bacillus subtilis 93151 are
      overlapping genes, which encode two proteins ProB and ProA. A restriction enzyme
      site was inserted in the overlapping region of proB and proA genes from a salt
      tolerant mutant of B. subtilis 93151, and a fusion gene was constructed by
      cloning proB and proA genes respectively. SDS-PAGE analysis showed that a novel
      protein with molecular mass of 85 kD was observed. When expressed in E. coli,
      enhanced intracellular concentrations of free proline and osmotolerance of the
      strain carrying the fusion gene were observed, compared with the control host
      cell harbouring a plasmid encoding the separate ProB and ProA.

PMID- 15847157
TI  - [Detection of Mobiluncus species by special primer amplification and 16S DNA
      sequence analysis].
AB  - Bacterial Vaginosis (BV), a microecological disease leaded by overgrowth of the
      vaginal bacteria, is one of the Polymicrobial Diseases. The close relationship
      between BV and Mobiluncus ssp. was recognized gradually. But it is difficult to
      get the pure culture of this anaerobic bacterium because of its rigorous
      requirement for growth conditions. The vaginal discharge came from the BV animal
      model--Rhesus monkey was cultured in anaerobic environment. The 16S rRNA gene was
      amplified and sequenced using mobiluncus-specific primers. Mobiluncus ssp,
      closely related to Mobiluncus mulieris, were detected, by comparing with the 16S
      rRNA genes in the GenBank.

PMID- 15847158
TI  - [Effect of recombinant plasmid of Helicobacter pylori ureB gene on gastric
      epithelial cell].
AB  - To investigate the effect of recombinant plasmid of Helicobacter pylori ureB gene
      on gastric epithelial cell. The full length sequence of ureB gene from NCTC11637
      was amplified by PCR. The recombinant plasmid was constructed by cloning the open
      reading frame (ORF) of ureB into the eukaryotic expression vector pcDNA3.1, and
      was transfected SGC-7901 cells, then the clones resisting Hygromycin were
      screened. mRNA expression of ureB of transfected cells was detected by RT-PCR.
      The effect of recombinant plasmid of Hp ureB gene on cell phenotype was observed
      by fluorescence strain, on proliferation by MTT, on apoptosis and cell cycles by
      flow cytometry, respectively. The positive clones of ureB (SureB) appeared cell
      membrane budding and cell shrinkage. MTT assay showed there was no statistic
      significance between the SureB and SpcDNA3.1 which were transfected only by
      pcDNA3.1 (P > 0.05), suggesting that the growth of SureB were not inhibited. The
      apoptosis rate of SureB was higher than that of SpcDNA3.1 (P = 0.007). Analysis
      for cell cycle showed that in SureB cells the proportion of S phase increased,
      the proportion of both G2/M and G0/G1 phase decreased. Positive transfection of
      ureB gene into SGC-7901 can change cell phenotype and induce cell apoptosis.

PMID- 15847159
TI  - [Construction of a multi-copy Pichia expression vector and expression of human
      brain-derived neurotrophic factor in Pichia pastoris].
AB  - A pPICZ alpha1 vector was reconstructed with pPICZ alpha vector and PCR product
      of His4-Kan sequence from pPIC9K vector. The sequence encoding human brain
      derived neurotrophic factor (hBDNF) was inserted into pPICZ alpha1. The
      expression vectors carrying 1, 2, 3, 6 copies of expression cassettes were
      constructed and transformed into Pichia pastoris GS115 respectively. The
      transformants were screened with G418/Zeocin and induced by 0.5% methanol, and
      the results of SDS-PAGE confirmed that the expression protein was about 14 kD and
      the percentage of the protein was about 20% of the total secreted protein. ELISA
      and Western blot analysis demonstrated that the protein could be specifically
      combined with chicken antibodies to human-BDNF.

PMID- 15847160
TI  - [Transformation of Volvariella volvacea with a thermal hysteresis protein gene by
      particle bombardment].
AB  - A cDNA encoding a thermal hysteresis protein was isolated from the Swedish Arctic
      insect spruce budworm by RT-PCR amplification. Volvariella volvacea strain V34
      was transformed with this cDNA through particle bombardment. PCR detection and
      Southern blotting analysis show that the thermal hysteresis protein gene is
      integrated into Volvariella volvacea genome. Cold stress assay reveals that
      transgenic Volvariella volvacea lines exhibit stronger cold tolerance than host
      strain. The morphological observation of transgenic Volvariella volvacea lines
      shows that growth rates of most Volvariella volvacea transformants are
      significantly slower than that of negative control strain. And hypha of most
      Volvariella volvacea tansformants is thinner than host strain's hypha.
      Transformant screening result indicates that three-round of selection procedure
      with first selection on PDSA solid selective medium followed by second and third
      selection in PDSB liquid selective medium is favorable to get genuine
      transformants and to eliminate false transformants. Cold tolerance assay of
      transgenic Volvariella volvacea F1 generation demonstrates that the progeny of
      transgenic Volvariella volvacea still possesses stronger cold tolerance than non
      transformed host strain. This suggests that the cold tolerant characteristic of
      transgenic Volvariella volvacea is meiotically stable between generations.

PMID- 15847161
TI  - [Cloning, expression of the gene of dehydrochlorination of BHC from enrichment
      and its degradation experiment].
AB  - A high effective enrichment that could degrade four isomers of BHC completely was
      got from the soil polluted by gamma-BHC, but the pure culture was not obtained
      yet. The 471 bp sequence of linN was amplified from the total DNA of enrichment
      by polymerase chain reaction (PCR). The nucleotide sequence analysis showed that
      the linN gene had high homology with reported linA up to 99%. Then the amplified
      fragment linN was cloned in the proper orientation into the site between Nde I
      and Hind III of pET-29alpha via restriction endonuclease Nde I and Hind III. The
      recombinant was transformed into its host E. coli strain BL21 and a recombinant
      protein of about 17 kD was highly expressed and showed high ability of degrading
      gamma-BHC after induced by IPTG. The expressed protein occupied about 30% of the
      total bacterial protein. The cell extracts also showed some ability of
      degradation of gamma-BHC. It offered basic theory for the isolation of pure
      culture and the construction of genetic engineering microorganisms.

PMID- 15847162
TI  - [Molecular characteristics of DNA-A of tomato leaf curl Guangdong virus isolate
      G2].
AB  - Virus isolate G2 was isolated from tomato plants showing leaf curl symptoms in
      Guangdong. The complete nucleotide sequence of G2 DNA-A was determined to be 2744
      nucleotides encoding six potential ORFs, with two (AV1 and AV2) in virus sense
      and four (AC1, AC2, AC3 and AC4) in complementary sense. G2 DNA-A has a typical
      characteristics of Begomovirus genome organization. BLAST results showed that G2
      DNA-A belonged to the Begomovirus of Geminiviridae. Pairwise comparisons of G2
      DNA-A with those of other 41 begomoviruses indicated that G2 DNA-A was most
      closely related to that of Papaya leaf curl China virus isolate G10 (PaLCuCNV
      [G10]) (82.8% sequence identity). The intergenic region (IR) of G2 differed to
      great extent with other begomoviruses (30.9%-81.8% nucleotide sequence identity);
      when individual encoded proteins were compared, the CP of G2 had relatively high
      amino acid sequence identity (77.6%-99.2%) with other begomoviruses whereas the
      AC4 of G2 had less amino acid sequence identity (43.5%-78.8%). Phylogenetic
      analysis based on the DNA-A sequences also showed that G2 was less related to the
      reported begomoviruses. These results revealed that G2 infecting Guangdong tomato
      might be a previously unreported species of Begomovirus, for which the name
      Tomato leaf curl Guangdong Virus (ToLCGDV) is proposed.

PMID- 15847163
TI  - [Generation of attenuated H5N1 and H5N2 subtypes of influenza virus recombinants
      by reverse genetics system].
AB  - The HA connecting peptide at cleavage site, PQRERRKKR / GL, of an H5N1 subtype
      avian influenza virus (AIV) was replaced with PQRESR / GL, and then the modified
      HA gene was cloned into the transcription/expression vector, pHW2000,
      constructing a plasmid named pHW524-HA. The NA (N1) gene from the H5N1 virus and
      the NA (N2) gene from an H9N2 AIV were also cloned into pHW2000 separately,
      resulting in plasmids pHW506-NA and pHW206-NA. With the organization of pHW524
      HA, pHW506-NA or pHW206-NA, and six plasmids containing internal genes from
      A/WSN/33 backbone virus, two transfectants, H5N1/WSN and H5N2/WSN, were
      subsequently generated by eight-plasmid system. After 15 consecutive passages in
      embryonated eggs, the two recombinants grew up to high titers of 1:2(9) in
      hemagglutination test with no changes in nucleotide sequences of the surface
      genes detected. Both the recombinant viruses belonged to mildly pathogen when
      evaluated by the pathogenicity test in six-week-old SPF chickens. H5N2/WSN
      recombinant virus was obviously less pathogenic than H5N1/WSN virus for
      embryonated chicken eggs. This presentation showed that the reverse genetics
      system is a very useful tool for studying the construction and function of
      individual genes and for the generation of virus as vaccine candidate.

PMID- 15847164
TI  - [The prokaryotic expression and the establishment of the putative indirect ELISA
      assay for the HA gene for avian influenza virus (AIV) H5N1 subtype].
AB  - Using a pair of specific primers designed according to the relevant nucleotide
      sequence from GenBank, the HA1 gene of H5N1 subtype AIV was amplified with PCR
      method. The PCR product was cloned into pET-32a(+) to get a prokaryotic
      recombinant plasmid pET-HA1. The target gene was successfully expressed in the
      host cell BL21 (DE3) when induced with IPTG. The expression was optimized with
      proper inducing conditions of 0.8 mmol/L IPTG and 3 hours induction. The highest
      expression of the target protein added up to 32.7% of the total bacterial
      protein. Western blot analysis proved the recombinant protein has good reactive
      ability against H5N1 subtype AIV positive serum. The optional working
      circumstances for the iHA-ELISA assay (antigenicity concentration: 4 microg/mL;
      serum dilution: 1:200) was tried out with chess titration. The positive criterion
      of this ELISA assay is OD(the tested serum) > 0.5 and OD(the tested serum)/OD(the
      negative serum) > 2.0.

PMID- 15847165
TI  - [Study on the self-assembly ability of expressed capsid protein of rabbit
      haemorrhagic disease virus that fused with foreign epitope at the N-terminus].
AB  - The RHDV capsid protein (VP60) gene was first subcloned into the transfer plasmid
      pBLUEBACHIS2B located downstream of a 6 * HIS tag, then the recombinant transfer
      plasmid DNA were cotransfected Sf 9 cells with Bac-N-Blue DNA and purified for
      cloned recombinant baculovirus by plaque assay. The expression of fused-VP60 gene
      was analyzed by SDS-PAGE and Western blot. A specific 69 kD protein band was
      obtained. Observed under electron micrography, the recombinant baculovirus
      expressed VP60 protein assembled into viruslike particles which were
      morphologically and antigenically similar to native RHD virus but did not package
      RNA. The close-to-native conformation of the VLPs was also supported by the
      haemagglutination test, in which recombinant VLPs, like RHDV, agglutinated human
      blood type O erythrocytes.

PMID- 15847166
TI  - [Identification and comparison of neutralizing epitopes of glycoprotein E(rns) of
      classical swine fever virus].
AB  - Structural and envelope glycoprotein E(rns) (gp48) of classical swine fever virus
      (CSFV) is the second antigenic protein being responsible for eliciting
      neutralizing antibodies and conferring protective immunity. Infection of cells
      with CSFV is mediated by the interaction of glycoprotein E(rns) and E2 with the
      cell surface receptors. The glycoprotein E(rns) has been shown to contain RNase
      activity, which plays a role in the viral life cycle and is also involved in
      virus neutralization. Neutralizing epitopes of glycoprotein E(rns) had been
      mapped by screening a 12-mer random peptide phage display library using the
      neutralizing monoclonal antibodies (MAbs) 1B5, b4-22 and 24/16, raised against
      CSFV strain alfort T bingen and reacted with glycoprotein E(rns). Three major
      epitope (mimotope) motifs, WxNxxP, DKNR (Q) G and A (T) CxYxKN (around amino acid
      position aa351-aa356 or aa348-aa350, aa384-aa386 and aa322-aa323, aa380-aa386 of
      glycoprotein E(rns) of CSFV) were identified respectively and characterized
      immunologically by the MAbs, 1b5, b4-22 and 24/16. MAbs b4-22 and 24/16 shared a
      part of binding motif sequence KN, and recognized the similar antigenic domain on
      the glycoprotein E(rns) but showed a distinct pattern of flank sequence and
      reactivities with the mimotopes by Western blot and inhibition of
      immunofluorescent antibody analysis.

PMID- 15847167
TI  - [Construction of minigenome of Newcastle disease virus of goose origin and its
      preliminary application].
AB  - On the base of obtaining the full length genome sequence of a Newcastle disease
      virus (NDV) isolated from goose, the minigenome was constructed by replacing all
      the encoding region with the reporter gene of enhanced green fluorescent protein
      (eGFP), except the virus regulating sequences relating to replication,
      transcription and packing of virus genome. The reporter gene could be expressed
      after it was transfected into the HEp-2 cells infected with helper virus of NDV.
      This result indicated that the minigenome could be translated by the NDV NP, P
      and L proteins provided by helper virus. Furthermore, the support plasmids
      expressing NDV NP, P and L protein were constructed respectively and the function
      of these plasmids was identified using the minigenome. Additionally, the virus
      rescue system was optimized by changing the infection dose of the recombinant
      vaccinia virus expressing T7 RNA polymerase. The work mentioned above will
      accelerate greatly the rescue of NDV and other relative research.

PMID- 15847168
TI  - [Application of a metabolic-pathway-analysis based breeding strategy enhances the
      production of pyruvate by Torulopsis glabrata].
AB  - To further enhance the pyruvate productivity by multi-vitamin auxotrophic yeast
      Torulopsis glabrata, a breeding strategy aiming at decreasing the activity of
      pyruvate decarboxylase but increasing the activity of acetyl-CoA synthetase was
      developed based on analysis of pyruvate-related metabolic pathways.
      Nitrosoguanidine mutagenized cells of T. glabrata WSH-IP303 were screened for
      mutants that require acetate for complete growth on glucose minimum medium. A
      mutant, T. glabrata CCTCC M202019, produced pyruvate 21% higher than that of the
      parent strain and was genetically stable in flask cultures, was selected as a
      working strain. To elucidate the metabolic changes that led to the increase of
      pyruvate production, the activities of enzymes that involved in pyruvate-related
      metabolic pathways of the mutant and the parent strain were determined. Enzymatic
      analysis revealed that, compared with the parent strain WSH-IP303, the activity
      of pyruvate decarboxylase of the mutant strain CCTCC M202019 decreased by roughly
      40%, while the activity of acetyl-CoA synthetase of the latter increased by
      103.5% or 57.4%, respectively, in the presence or absence of acetate. When 6 g/L
      sodium acetate was added to the medium, pyruvate production by the mutant strain
      CCTCC M202019 reached 68.7 g/L at 62 h (yield on glucose, 0.651 g/g) in
      fermentations performed in a 7-L jar fermentor, indicating the shortage of
      cytosolic acetyl-CoA resulted from the disruption of pyruvate decarboxylase was
      properly compensated by the increase of the activity of acetyl-CoA synthetase.

PMID- 15847169
TI  - [Influence of Mn2+ on the biotechmycin fermentation].
AB  - The effect of Mn2+ on the biotechmycin fermentation by Bioengineered strain WSJ-l
      195 was studied. In the fermentation process, Mn2+ could improve the biological
      potency significantly, especially when Mn2+ concentration was 5 mmol/L added at
      24 h. The pH profile of fermentation broth decreased gradually after 5 mmol/L
      Mn2+ supplemented at 24 h, and PMV was lower than that of the control sample.
      Further research about the influence of Mn2+ on the biosynthesis of biotechmycin
      was carried out in the aspect of organic acids. The results showed that
      concentrations of organic acids in a fermentation with 5 mmol/L Mn2+ supplemented
      at 24 h had been changed greatly, especially the concentration of propionic acid,
      of which the highest value was about 6 times as that in the control sample at 84
      h. In addition, it was found that the yield of biotechmycin could be improved
      significantly with tiny amount of propionic acid added. Therefore, it can be
      concluded that Mn2+ has profound influence on the biosynthesis of biotechmycin:
      it enriches the biotechmycin precursor pool such as propionic acid and thus
      improves the yield of biotechmycin.

PMID- 15847170
TI  - [Involvement of MAPKs and NF-kappaB pathways in Pseudomonas pyocyanin-induced
      interleukin-8 expression by human airway epithelial cells].
AB  - To investigate the molecular mechanisms of signaling transduction by which
      Pseudomonas pyocyanin induces IL-8 expression in human airway epithelial cells,
      A549 and SPC-A-1 cells were challenged with P. aeruginosa conditioned medium or
      pyocyanin. Chemokine interleukin-8 (IL-8) release from the challenged cells was
      measured by ELISA, and Western blot was performed to analyze the degradation of
      IkappaB-alpha and the phosphorylation of MAPKs (mitogen-activated protein
      kinases) in the extracts from cells stimulated with pyocyanin. Both of P.
      aeruginosa conditioned medium and pyocyanin remarkably increased IL-8 expression
      by human airway epithelial cells. Degradation of IkappaB-alpha was found shortly
      after A549 cells were stimulated with pyocyanin. Western hybridization analysis
      also demonstrated that pyocyanin caused phosphorylation of MAPKs including
      ERK1/2, p38 and JNK in A549 cells. Pretreatment of A549 cells with U0126 (10
      micromol/L), a selective inhibitor of MEK1/2 (ERK1/2 kinase) or with SB203580 (10
      micromol/L), a specific inhibitor of p38 MAPK, diminished the pyocyanin-induced
      IL-8 production. These findings suggest that Pseudomonas pyocyanin can increase
      IL-8 expression by human airway epithelial cells through MAPKs signaling pathways
      and the activation of NF-kappaB is also involved in this process.

PMID- 15847171
TI  - Survey of coastal mangrove fungi for xylanase production and optimized culture
      and assay conditions.
AB  - Xylanase activity was detected among 34 of 77 fungal isolates derived from
      decaying wood, debris and soil samples collected in coastal mangrove environment
      of Hong Kong. Of those, three isolates CY2809 (Staganospora sp.), CY4786 and
      CY5040 were chosen for comparison of xylanase production in parallel to HU5048
      (Aspergillus awamori), a terrestrial, highly productive isolate. Based on the
      assessment of mycelial biomass, xylanase activity and content of xylose
      equivalent reducing sugars in their liquid cultures, the isolate CY4786 was best
      for xylanase production in a basal medium containing birchwood xylan (10.0 g/L)
      as a sole carbon source, yeast extract (2.5 g/L) and sea salts (15.0 g/L) with
      initial pH 7.8. When assayed at the optimized regime of 50 degrees C and pH 4.6,
      the activity of xylanase produced by CY4786 in 7d liquid culture at 25 degrees C
      reached 1.07 x 10(4) unit/mL. The results indicate that the mangrove fungi act as
      hemicellulose decomposers in the mangrove environment where highly xylanase
      productive isolates can be searched for exploitation. A discussion is given on
      the possible use of the content of xylose-equivalent reducing sugars as an index
      to simplify conventional xylanase activity assay method for fungal isolate
      survey.

PMID- 15847172
TI  - [Breeding, optimized fermentation and enzymatic properties of a Bacillus
      licheniformis mutant producing cyclomaltodextrin glucanotransferase].
AB  - A bacterial strain 403 selected from various soil was found to produce
      cyclomaltodextrin glucanotransferase (CGTase) with an activity of 0.95 U/mL after
      96 h submerged incubation. A mutant, Bacillus licheniformis CLS403, obtained by
      means of ultraviolet radiation and diethyl sulfate, enhanced CGTase production by
      43% (1.36 U/mL). The optimized conditions for CGTase production of mutant were
      soluble starch as carbon source, ammonium nitrate as nitrogen source, 35 degrees
      C and pH 6.5 for incubation. Under these conditions, the production of CGTase by
      the mutant in submerged peaked at the period of 96 h incubation, two days later
      than bacterial biomass peak. The resultant CGTase reacted best at 55 degrees C
      and pH 6.0, and had activities > 90% after 1 h maintenance at 50 degrees C with
      pH 6.0-7.5. Addition of Ca2+ in the reaction largely enhanced stability of the
      CGTase activity at 55 degrees C. Based on HPLC analysis, the products of starch
      hydrolyzed by the CGTase of B. licheniformis CLS403 included much more alpha
      cyclodextrin than beta-cyclodextrin but no gamma-cyclodextrin. The total yield of
      cyclodextrin from starch reached 29.8% with the ratio of the two cyclodextrins
      2.47:1.

PMID- 15847173
TI  - [Effects of carnitine acetyltransferase gene knockout on long chain dicarboxylic
      acid production and metabolism of Candida tropicalis].
AB  - Candida tropicalis can assimilate n-alkane as a sole carbon source and produce
      dicarboxylic acids (DCAs). The synthesis of DCAs is thought to be reduced by beta
      oxidation. Carnitine acetyltransferase (CAT) is the major enzyme to transfer DCAs
      into beta-oxidative pathway, then DCAs would be catalyzed to generate ATP to
      supply cells with energy. A homologous recombination plasmid was constructed, in
      which CAT gene was disrupted by inserting hygromycin B resistance gene. This
      plasmid was used to transform Candida tropicalis wild type strain F10-1, and one
      single CAT gene knockout strain was obtained. Comparing with the wild type, the
      recombinant increased DCA13 yield and molar conversion of alkane by 13.0% and
      11.8%, respectively, and decreased unnecessary consumption of DCAs in beta
      oxidation.

PMID- 15847174
TI  - [Impact of water content and temperature on the shelf-life of Beauveria bassiana
      conidia stored in dark].
AB  - Batches of Beauveria bassiana SG8702 conidia as powder with water content (Cw) of
      1.12, 4.73, 7.23, 9.84 and 14.11% were stored in dark at 4 and 25 degrees C
      during an 18-mon period and monitored at 15-day intervals for viability in order
      to determine their shelf-lives under controlled conditions. The Cw was found
      significantly affecting the viability at each temperature. Stored at 4 degrees C,
      conidial viability always fluctuated above 91% during the first 16 months among
      the Cw treatments of 1.12%-9.84% with no significant difference from one to
      another until at the end of 18 months, when the 9.84% Cw treatment had a
      significantly lower viability than other treatments with lower Cw. The viability
      in the high Cw treatment (14.11%) was significantly smaller than those in the Cw
      treatments of 1.12%-9.84% from month 6 onwards and dropped to only 24.2% at the
      end of 12 months. Stored at 25 degrees C, however, the viabilities differed
      significantly among the Cw treatments of 1.12%-9.84% on months 3 and 6,
      respectively, with a remaining viability of only 17.6% in the 9.84% treatment at
      the end of 6 months. The observed viabilities (Vc) depending on the (Cw) over the
      time of storage (Ts, months) at each temperature were well fitted to a modified
      survival model with the coefficients of determination exceeding 0.85. When a
      viability of 90% was expected on a basis of the fitted model, the shelf-life of
      B. bassiana conidia stored at 4 degrees C was estimated as 7.3 months at Cw =
      12%, 11.2 at Cw = 10%, 14.9 at Cw = 9%, 21.0 at Cw = 8%, 33.0 at Cw = 7%, and
      65.5 at Cw = 6%, respectively. Thus, the Cw for long-term storage at 4 degrees C
      could be controlled at < or = 8%. In contrast, for an expected viability of 80%
      at 25 degrees C, the shelf-life was estimated as only 1.7 months at Cw = 10%, 2.3
      at Cw = 8%, 3.0 at Cw = 6%, and 3.8 at Cw = 4%. Obviously, an expected 3-month
      shelf-life required Cw < or = 5%.

PMID- 15847175
TI  - [Capsid-targeted viral inactivation for dengue virus infection].
AB  - To explore the feasibility of capsid-targeted viral inactivation for dengue virus
      infection, a newly-discovered antiviral strategy, a mammalian cell line stably
      expressing staphylococcal nuclease fused to the capsid protein of dengue 2 virus
      was established and the effects on the production of infectious virus particles
      were examined. The results presented evidence that the enzymatically active
      staphylococcal nuclease fused to capsid protein could be incorporated into the
      nascent virions during wild virus assembly, resulting in degradation of viral
      genomic RNA and decrease in infectivity. Comparing the effects of incorporated SN
      and SN*, an enzymatically inactive missense mutant form of SN, on the infectivity
      of progeny virions, nucleolytic activity of incorporated SN was responsible for
      the major antiviral effects. These results paved the road of developing capsid
      targeted viral inactivation as a new antiviral strategy against dengue.

PMID- 15847176
TI  - [Monoclonal antibodies prepared and used for detection of acute virus necrobiotic
      disease virus in scallop Chlamys farreri by indirect ELISA].
AB  - For developing monoclonal antibodies against acute virus necrobiotic disease
      (AVND) virus, mice of Balb/c strain were immunized with AVND virions which were
      isolated from the infected scallop Chlamys farreri. The spleen cells from
      immunized mice were then fused with NS-1 myeloma cells and the hybridomas were
      screened by means of enzyme-linked immunosorbent assay (ELISA) and
      immunofluorescence assay (IFA). Finally, 4 stable MAbs of IgG isotype were
      obtained. Moreover, the combined position of these 4 MAbs to this virus was
      examined by immunogold electron microscopy (IEM). The results demonstrate that
      all 4 MAbs recognized epitopes on the envelope of the virions. Subsequently, a
      MAb-based ELISA was developed and used for detection of the infection rate and
      densities of the scallops which were sampled during different seasons from mid
      April to mid-October, 2003. The result exhibited that both of the infection rate
      and infection densities sharply rose in mid-July and reached to the spikes, which
      right corresponds with their mortality during this period.

PMID- 15847177
TI  - [Archaeal diversity associated with sponge Pachychalina sp. analyzed by culture
      independent approach].
AB  - With culture-independent approach, microbial total DNA was directly extracted
      from Pachychalina sp. Using the total microbial DNA as template, archaeal 16S
      rDNAs were amplified by PCR with universal primers. Amplified products were
      cloned into T-vector and secondarily amplified by PCR. Then the secondarily
      amplified products were purified to be further characterized by termed ARDRA
      (amplified rDNA restriction analysis). According to the enzyme restriction
      mapping, the apparent difference among them were disclosed. Furthermore eight
      archaeal cloned partial sequences were acquired and built up a phylogenetic tree.
      In the phylogenetic tree, the eight archaea belonged to Methanogenium
      organophilum and Methanoplanus petrolearius, but the 16S rDNAs similarities among
      them and those archaea registered in RDP Database didn't excess to 90%. It means
      that they maybe represent some novel archaeal groups.

PMID- 15847178
TI  - [A simple and visible assay for cre recombinase activity in Escherichia coli by
      using two incompatible plasmids].
AB  - The Cre/loxP system derived from bacteriophage P1 is widely used to carry out
      complex manipulations of DNA molecules both in vitro and in vivo. In order to
      further characterize and modify the Cre/loxP system, a convenient method for
      assaying the recombination efficiency is needed. A simple and visible assay is
      described, in which two incompatible plasmids, separately carrying the cre gene
      and loxP-flanked gfp gene, were co-transferred into E. coli. The cre gene was
      inserted into a kanamycin-resistant bacterial expression vector, designated
      pET30a-Cre. The gfp gene, flanked by directly repeated loxP sites, was cloned
      into an ampicillin-resistant expression vector to generate pET23b-loxGFP. E. coli
      BL21 (DE3) was cotransformed with pET30a-Cre and pET23b-loxGFP, and cultured in
      the presence of both ampicillin and kanamycin. Under UV illumination, the Cre
      mediated recombination events can be easily detected. The fidelity of
      recombination was verified by SDS-PAGE analysis and restriction analysis followed
      by DNA sequencing. Thus, this cotransformation method provides a straightforward
      assay that can be used to modify the Cre/loxP system.

PMID- 15847179
TI  - [Agrobacterium tumefaciens-mediated transformation of Chaetomium globosum and its
      T-DNA insertional mutagenesis].
AB  - Agrobacterium tumefaciens-mediated transformation is a routine method in the
      genetic transformation of a wide range of plant species, and so far, its
      application has been extended to the transformation of yeasts, fungi and even
      human cells. By using this transformation system, filamentous fungus Chaetomium
      globosum was successfully transformed with an efficiency of 60-180 transformants
      per 10(7) spores. PCR and Southern analysis showed that the T-DNA was integrated
      into the genome. Among of the examined transformants contained a single copy, and
      was stable through mitotic cell division. The transformation system mediated by
      Agrobacterium tumefaciens may prove to be a powerful tool for the filamentous
      fungi transformation and functional genomic study with its high transformation
      frequency, simplicity of T-DNA integration, and genetic stability of
      transformants.

PMID- 15847180
TI  - [Cloning, expression of the CP gene and antiserum preparation of zucchini yellow
      mosaic virus infecting Benincasa hispida Cogn. var. chieh-qua How].
AB  - A Guangzhou isolate of ZYMV infecting Benincasa hispida Cogn. var. chieh-qua How
      was identified by indicator tests and partial sequence amplification. The coat
      protein (CP) gene of this virus was amplified by RT-PCR, and ligated to the
      expression vector pET-22b(+). The recombinant plasmid pET-ZCP was transformed
      into E. coli BL21 (DE3) and then induced to express by IPTG. It was shown that
      the CP gene was highly expressed by SDS-PAGE and Western blot analysis. The
      molecular weight of the recombinant protein was about 33.0 kD. Antiserum with
      high specificity was produced after the rabbit was immunized with purified
      recombinant protein, and the titer was determined to be 1/4096 by antigen coating
      plate-ELISA (ACP-ELISA).

PMID- 15847181
TI  - [Integrative expression of XynB of Aspergillus niger UV-11 in industrial yeast].
AB  - The cDNA sequence of beta-xylanase gene (xynB) was cloned from Aspergillus niger
      UV-11. It was inserted into the yeast expression vector and the recombinant
      plasmid pAX2 was obtained. The plasmid pAX2 was introduced into an industrial S.
      cerevisiae 2.346 and integrated into yeast genome by co-transformation of a
      YEPtype plasmid pBEJ16 carrying G418 resistance. The stable engineered yeast
      strain XY2 was obtained. It could express and secret extracellular xylanase, and
      enhance the alcohol production in wheat flour fermentation compared with the host
      strain S. cerevisiae 2.346.

PMID- 15847182
TI  - [Integration and expression of sdh gene in Escherichia coli].
AB  - The chloramphenicol-resistant cassette with short shared sequences of ptsG gene
      on both ends was PCR-generated from plasmid pKF3 and ligated to pMD18-T to
      construct pMD18-PC. The sdh gene for sorbose dehydrogenase was generated from
      plasmid pQE60-SDH and inserted into pMD18-PC, then pMD18-PC-SDH was constructed.
      It was digested with Pvu II and the target fragment ptsG1-cat-sdh-ptsG2 was
      recovered and electroporated into Escherichia coli JM109/pKD46. Homologous
      recombination between linear DNA cassettes and Escherichia coli chromosomes took
      place by Red recombination. The detection result showed that the integron JM109s
      was of sorbose dehydrogenase activity. The PCR products assay using the upstream
      and downstream sequences of ptsG gene as primers and JM109s genomic DNA as
      template, indicated that sdh gene had been integrated at the ptsG gene site in
      Escherichia coli.

PMID- 15847183
TI  - [Cloning and expression of endoglucanase of marine cold-adapted bacteria
      Pseudoalteromonas sp. MB-1].
AB  - The cold-adapted gram-negative rod bacterium MB-1 which could secret cellulase
      was screened from mud of the bottom of the Huanghai. According to the sequence of
      16S rDNA, this bacterium screened was identified as one species of
      Pseudoalteromonas and was named as Pseudoalteromonas sp. MB-1. The gene celA
      encoding cold-adapted endogluanase was cloned and then jointed to pGEX-4T-1 to
      construct expression plasmid pGEX-celA which was expressed in E. coli BL21.
      Analysis to the supernatant of E. coli sonicate revealed that the concentration
      of GST-CelA was about 78.5 mg/L. Properties of the fusion enzyme of GST-CelA
      including the optimum temperature at 35 degrees C and the optimum pH about 7.2,
      showed that this fusion enzyme still belonged to cold-adapted enzyme and neutral
      enzyme. The result lays solid base for the fundamental theory and application
      research on cold-adapted cellulase from Pseudoalteromonas sp. MB-1.

PMID- 15847184
TI  - [Methanogens and manipulation of methane production in the rumen].
AB  - Methanogens belong to the kingdom of Euryarchaeota in the domain of Archaea. They
      are characterized by their ability to produce methane under anaerobic conditions.
      Methane production in the rumen represents a loss of energy for the host animal,
      and, in addition, methane eructated by ruminants may contribute to a greenhouse
      effect or global warming. Reduction or elimination of methanogenesis in the rumen
      has been touted as a way of improving animal production and may marginally
      benefit to control of anthropogenic release of methane. More and more scientists
      focus on ruminal methanogens and methanogenesis recently. Authors summarized the
      manipulation of methanogenesis in the rumen, including defaunation, feed
      formulation, adding electron acceptors and stimulation of acetogens. The
      characteristics of methanogenic Archaea and the recent knowledge of the
      methanogenesis in the rumen were also reviewed in this article.

PMID- 15847185
TI  - [Progress on the vaccine for anthrax].
AB  - Bacillus anthracis is the causative organism of the potentially fatal disease
      anthrax, and the used vaccines have some disadvantages. There are new
      developments appeared for the Bacillus anthracis in recent years, such as anti-PA
      antibody kills the spore of Bacillus anthracis, mucosal immunization induces
      immune responses in both systemic and secretory immune compartments, Poly (gamma
      D-PGA) protein induce IgG antibodies to the vegetative bacteria, new pathogens
      were found by genomic analysis. The DNA vaccine and live vector vaccine will be
      the next generation vaccines for anthrax. It will have a shorter immunization
      schedule and will be greater protective efficacy than before.

PMID- 15847186
TI  - [Progress on microbial glyceride biosynthesis and metabolic regulation in
      oleaginous microorganisms].
AB  - Oleaginous microorganisms are small portion of organisms that have ability to
      accumulate lipids over 20% of their biomass. These species can transform
      renewable material into microbial oil with similar fatty acid composition to that
      of plant-based oil. Some organisms may also produce glycerides with high content
      of poly-unsaturated fatty acids. Therefore, microbial lipids are considered as
      potential oil resource. Summarized here are some features of oleaginous species
      and recent developments on their biosynthetic machinery and metabolic regulation
      mechanism.

PMID- 15847187
TI  - Perspectives. The bad news: unless medical practice is reengineered, I.T. won't
      help.

PMID- 15847188
TI  - [Austrian Society for Internal Medicine and Viennese Clinical Weekly/Acta Medica
      Austriaca: a fortunate symbiosis].

PMID- 15847189
TI  - The painful bone marrow edema syndrome of the hip joint.
AB  - In this issue of the WKW, Aigner et al have published that, for the first time, a
      conservative approach with iloprost has shown to be equally successful as the
      well-documented core decompression surgical approach in patients with BMES of the
      hip joint. The BME pattern on MR-imaging of the hip joint represents a common but
      unspecific finding, which may be associated with several diseases requiring
      different therapeutic strategies (Table 1). It is still controversial, whether
      BMES of the hip represents a distinct self-limiting disease also known as
      transient osteoporosis, transient marrow edema, or algodystrophy, or merely
      reflects a subtype of ON. Since prognosis and therapeutic consequences vary
      significantly, differential diagnosis between BMES, CRPS and ON is of clinical
      interest (Table 2). Both, BMES and ON show similar ON risk factors and a male
      prevalence, while classical CRPS has a history of trauma and a prevalence among
      females. Clinical presentation of BMES and ON is similar with typical mechanical
      pain and prevalence of the hip joint. In contrast, classical CRPS shows a diffuse
      and burning pain in combination with trophic and vasomotor signs, mainly in the
      hands and feet. Imaging patterns of BMES are more diffuse, across the entire
      femoral head, while focal and subchondral in ON. In both, the patterns are
      limited to the femoral head. In contrast to classical CRPS, the imaging changes
      are located in all periarticular bones, and the soft tissues are always affected.
      The histological bone marrow changes are similar in all three diseases, but with
      abundant new bone formation in BMES and CRPS, whereas in ON only limited new bone
      formation surrounds the focal necrosis with a sclerotic rim. Protected weight
      bearing and treatment with iloprost for BMES, but operative treatment for ON, and
      a sophisticated physiotherapy for CRPS in combination with iloprost are the
      preferred treatment strategies in our institution.

PMID- 15847190
TI  - [Sentinel node biopsy in breast cancer: techniques and indications].
AB  - Sentinel node biopsy (SNB) has proved to be a useful and accurate procedure for
      lymph node staging in breast cancer and melanoma and should be standard of care
      in the treatment of these tumors. In other malignancies (colon, rectum, stomach,
      esophagus, head and neck and thyroid, cervix uteri) it is still under
      investigation. SNB in breast cancer was accepted as a sole and reliable
      diagnostic method in breast cancer from the panel of distinguished experts at the
      8th international conference of primary therapy of early breast cancer 2003 in
      St. Gallen. Combination of the current techniques with radiocolloids and blue
      dye, applicated superficially (intradermal, subdermal, peri- and subareolar) and
      deeply (peritumoral, intratumoral, subtumoral) enables high identification rates
      and negative predictive values. It should be performed by teams consisting of
      surgeons, pathologists and nuclear medicine specialists with appropriate training
      and experience. Accepted indications are uni- and multifocal tumors smaller than
      3 cm without suspicious findings in the axilla, furthermore SNB is indicated in
      patients with large ductal carcinoma in situ (>2cm) and/or with assumed
      microinvasion. Albeit SNB could be shown to be safe after preoperative
      chemotherapy and in multicentric breast cancer, due to lack of sufficient data it
      is still under discussion in these cases. Expedience of this procedure in other
      lymph node basins, along the mammaria interna vessels or in the infra- and
      supraclavicular region is considered to be at an investigative stage as well. SNB
      allows the pathologist to focus on a small number of nodes most likely to contain
      metastases. Application of serial sectioning and immunhistochemistry results in a
      more accurate staging than routine examination. Detection of additional
      micrometastases that are found in 10-15% leads to an upgrading from N0 to N1.
      Broad application and refurbishment led to scientific discussion of prognostic
      importance of micrometastases and its relevance according axillary dissection and
      adjuvant systemic treatment. Although many unicentric and multicentric
      observational studies validated by complete axillary dissection could demonstrate
      that SNB is accurate and suitable for all operable clinically node-negative
      breast cancers, longterm results and especially the incidence of axillary
      recurrence and its sequelae are outstanding. Findings of ongoing large
      prospective randomized trials like NSABP 32, Z0010 and Z0011 of the American
      College of Surgeons (ACOSOG), the AMAROS-Trial of the European Organisation of
      Research and Treatment of Cancer (EORTC) and the ALMANAC-Trial of the British
      Association of Surgical Oncology (BASO) will give a conclusive answer.
      Significant improvement in morbidity and quality of life measurements could be
      revealed several times in unicentric and even in muticentric studies like
      ALMANAC. Sentinel node biopsy is a team approach, requirements are good
      cooperation and well-defined stuctures of quality indicators and documentation.
      Participation in national clinical studies is recommended.

PMID- 15847191
TI  - Whole body bone scintigraphy after parachute accident.

PMID- 15847192
TI  - Bone marrow edema syndrome of the femoral head: treatment with the prostacyclin
      analogue iloprost vs. core decompression: an MRI-controlled study.
AB  - BACKGROUND: The purpose of this study was to assess the efficacy of the
      vasoactive drug iloprost in Bone Marrow Edema Syndrome (BMES) and to compare it
      to the results of a control group treated by core decompression. PATIENTS AND
      METHODS: 38 hips (36 patients) with BMES in the femoral head were investigated.
      In group A, 18 hips (17 patients; mean age 49 years) were treated with iloprost,
      a vasoactive drug that dilates arterioles and venules, reduces capillary
      permeability and suppresses platelet aggregation. The therapy comprised a series
      of five infusions with 20 microg iloprost over 6 hours on 5 consecutive days.
      Weight bearing was reduced for up to 3 weeks, depending on the severity of
      symptoms. In group B, 20 hips (19 patients; mean age 41 years) underwent surgical
      core decompression of the femoral head followed by 6 weeks of partial weight
      bearing. Both groups were evaluated clinically, radiographically and by MRI.
      RESULTS: In group A, one patient had to discontinue therapy on the first day
      because of severe headache. In the remaining patients the Harris Hip Score (HHS)
      improved from a mean of 64.7 points (range 44-89) before therapy to 97.0 points
      (83-100) after 3 months. MRI controls showed complete remission in all hips. In
      group B, the preoperative HHS improved from 53.7 points (31-82) to 95.1 points
      (39-100) after 3 months. MRI controls showed complete remission of BMES in 14
      hips, residual focal bone marrow edema in four hips and a small osteonecrotic
      area in two hips. In both groups the high level of clinical recovery was
      maintained at the last examination after a mean follow up of 11 months in group A
      and 12 months in group B. CONCLUSION: The parenteral application of iloprost can
      achieve equal or better results in the treatment of bone marrow edema syndrome of
      the hip compared to core decompression.

PMID- 15847193
TI  - Changes in Mcl-1 expression in rectal cancer in relation to neo-adjuvant
      radiotherapy.
AB  - BACKGROUND: Expression of the antiapoptotic protein myeloid cell leukemia-1 (Mcl
      1) may be disordered in malignancies of the rectum. High levels of Mcl-1 may
      correlate with unfavourable clinical outcome. AIM OF THE STUDY: The aim of the
      study was to determine the biologic significance and the prognostic value of the
      protein Mcl-1 in a group of patients with rectal cancer using immunohistochemical
      staining in archival specimens. PATIENTS AND METHODS: Expression of the Bcl-2
      family member Mcl-1 was determined in 23 rectal malignancies. Half of the
      patients with rectal cancer were treated with preoperative short-term radiation
      therapy of 25 Gy followed by radical surgery; the other patients were treated
      just with radical surgery. Differences in Mcl-1 expression between irradiated and
      non-irradiated rectal cancer cells were analysed immunohistochemically, and Mcl-1
      expression was correlated with overall survival. Induction of Mcl-1 expression by
      irradiation versus control in colorectal cancer cells was detected using Western
      blot. RESULTS: Mcl-1 was expressed at high levels in 35% of all specimens.
      Significantly stronger expression was detected in specimens of irradiated rectal
      cancer compared with non-irradiated tissues (p-value: 0.005). No association was
      seen between marker expression patterns and clinicopathological data of the
      respective patients. CONCLUSION: Our findings indicate that irradiated rectal
      cancer produces significantly higher levels of the antiapoptotic protein Mcl-1
      than non-irradiated rectal carcinoma. The data also suggest that the high level
      of Mcl-1 was induced by the radiotherapy. As Mcl-1 is an antiapoptotic regulator,
      its over-expression in irradiated rectal cancer could constitute a detrimental
      development antagonizing the potential benefit of adjuvant radiotherapy. Further
      evaluation of the correlation between Mcl-1 expression and overall survival seems
      warranted.

PMID- 15847194
TI  - Skin plugs in phlebotomy puncture for blood donation.
AB  - Contamination at the site of the donor's skin may occur despite proper
      disinfection, because pathogens in deeper regions (such as pores) may not be
      eliminated by skin disinfection. It is suspected that the cannula detaches
      fragments of tissue when it penetrates the skin; the tissue fragments may reach
      blood products and release pathogens there. In the present study we punctured
      piglet skin with cannulas commonly used for blood donation and performed
      histological as well as cytological investigations of the lavage fluid in the
      cannula to identify superficial skin cells and skin plugs. Histological specimens
      of the pierced skin showed frayed puncture sites with loosely attached tissue
      fragments. In the lavage fluid of the cannula, a collection of epidermal cells
      was found in one of 150 punctures. Our results confirm that the phlebotomy
      cannula may cause superficial tissue fragments to be punched out of the donor's
      skin during blood donation. This fact should be taken into account when devising
      methods to reduce bacterial contamination in blood products.

PMID- 15847195
TI  - Geriatric polytrauma.
AB  - BACKGROUND: compared to a younger population, the treatment of geriatric trauma
      victims is known to be associated with a higher mortality and morbidity. The
      objectives of this study are to assess the clinical course and outcome of
      multitrauma patients aged 65 years and over. In addition, a direct comparison
      between the geriatric trauma patients and the younger collective is performed.
      METHOD: our study includes all multitrauma patients treated between 1992 and 2001
      at a major urban trauma center. The major issues of this analysis are: injury
      severity, injury pattern, preclinical hemodynamics and intubation rate, operative
      treatment, ventilation time, outcome as well as incidence of multiorgan failure
      (MOF) and adult respiratory distress syndrome (ARDS). Out of these results,
      adults over 65 years of age (group B, n = 45) are compared to the younger group,
      ranging from 16 to 64 years of age (group A, n = 369). RESULTS: The preclinical
      intubation rate was comparable in both groups (A: 73.2%, B: 68.9%). Significantly
      more cases of group B were primarily shocked (A: 29.0%, B: 48.9%). The mean ISS
      was comparable in both groups (A: 34.0; B: 32.1). The younger group showed a
      significantly higher incidence of spine injuries (A: 21.1%; B: 6.7%). The number
      of emergency procedures (A: 24.2%; B: 24.4%) and operations during the first 24
      hours (A: 70.2%; B: 60.0%) was comparable in both groups. The older group showed
      a lower number of reconstructive operations (A: 57.6%; B: 35.6%). Geriatric
      trauma patients had a longer ventilation time compared to their younger
      counterparts (A: 13.0 days, B: 20.0 days). During ICU-therapy, the ARDS rate was
      comparable (A: 16.0%, B: 15.6%). In contrast, the incidence of MOF was
      significantly higher in group B (A: 7.1%; B: 17.8%). The older group showed a
      significantly higher mortality rate (A: 26.8%; B: 53.3%) as well as early
      mortality during the first 24 hours after admission (A: 16.3%, B: 31.11%).
      CONCLUSION: Despite similarity in injury severity and a comparable injury
      pattern, elderly multitrauma patients initially presented a higher rate of
      hemodynamic instability, had to be ventilated longer and had a higher mortality.

PMID- 15847196
TI  - Pneumonitis and pneumatoceles following accidental hydrocarbon aspiration in
      children.
AB  - Accidental ingestion and aspiration of hydrocarbons in children are common. Among
      the various clinical and pathological manifestations of hydrocarbon (HC)
      poisoning, pneumonitis is the most significant and occurs in up to 40% of
      children, whereas formation of pneumatoceles is believed to be a rare event. We
      report two children with HC pneumonitis and pneumatoceles as a reversible
      complication after ingestion and aspiration of lamp oil with very low viscosity.
      Patient 1, a 21-month-old boy, started to cough and developed tachypnea, sternal
      retractions and mild cyanosis immediately after aspiration. Patient 2, a 24-month
      old girl, was asymptomatic during the first days after the accident;
      subsequently, she started to cough and developed fever, dyspnea and chest pain.
      Chest x-ray and computed tomography revealed multiple patchy infiltrates in both
      cases; after several days, these confluent infiltrates developed into
      pneumatoceles. Both children were treated with antibiotics and steroids. They
      recovered within three and four weeks, respectively, with complete remission of
      the radiologic abnormalities and had an uneventful follow-up after discharge.

PMID- 15847197
TI  - [Recommendations on the diagnosis and multimodal primary therapy of rectal
      carcinomas 2004].

PMID- 15847198
TI  - Medical technology management: bridging the gap between theory and practice.
AB  - New medical technologies that offer to improve upon or completely replace
      existing ones are continuously appearing. These technologies are forcing
      healthcare policymakers to consistently evaluate new treatment options. However,
      emerging medical technology has been viewed as a significant factor in increasing
      the cost of healthcare. The abundance of new medical alternatives, combined with
      scarcity of resources, has led to priority setting, rationing, and the need for
      further technology management and assessment. Economic evaluation of medical
      technologies is a system of analysis within the framework of health technology
      assessment to formally compare the costs and consequences of alternative
      healthcare interventions. EEMT can be used by many healthcare entities, including
      national policymakers, manufacturers, payers and providers, as a tool to aid in
      resource allocation decisions. In this paper we discuss the historical evolution
      and potential of EEMT, the practical limitations hindering more extensive
      implementation of these types of studies, current efforts at improvement, and the
      ethical issues influencing ongoing development. The Medical Technologies
      Administration in Israel's Ministry of Health is given as an example of an entity
      that has succeeded in practically implementing EEMT to optimize healthcare
      resource allocation.

PMID- 15847199
TI  - Crohn's disease diagnosed by wireless capsule endoscopy in adolescents with
      abdominal pain, protein-losing enteropathy, anemia and negative endoscopic and
      radiologic findings.
AB  - BACKGROUND: Approximately one-fourth of new Crohn's disease diagnoses are made in
      individuals under the age of 20 years, in whom proximal Crohn's disease tends to
      be more common. OBJECTIVES: To describe the role of wireless capsule endoscopy in
      diagnosing isolated small intestinal Crohn's disease in two adolescents. METHODS:
      Wireless capsule endoscopy was performed in two adolescents with severe protein
      losing enteropathy and negative standard diagnostic workup. RESULTS: Wireless
      capsule endoscopy successfully diagnosed Crohn's disease with uncharacteristic
      presentations and negative radiographic and endoscopic findings in both patients.
      CONCLUSIONS: The non-invasiveness and ease in performance of capsule endoscopy on
      an ambulatory basis make this diagnostic modality especially advantageous for
      children.

PMID- 15847200
TI  - Overweight and obesity prevalence in Israel: findings of the first national
      health and nutrition survey (MABAT).
AB  - BACKGROUND: The prevalence of obesity has increased considerably in many
      countries in recent decades. OBJECTIVE: To describe the prevalence of overweight
      and obesity in the Israeli population, based on findings of the first national
      health and nutrition survey (MABAT). METHODS: This cross-sectional survey was
      carried out during 1999-2000. MABAT is based on a representative sample (n =
      3,246) of the general Israeli population aged 25-64 years. The current study
      population comprised those with complete data on measured weight and height (n =
      2,781). Participants were interviewed in person and had their weight and height
      measured by the interviewer. RESULTS: Over 50% of the study participants were
      women (n = 1,410); 76% were Jews and 24% Arabs. Most participants had an
      education of at least 12 years (72%). Body mass index > or = 30.0 was more
      prevalent in women compared to men (P < 0.001) in both population groups (Jews
      and Arabs). Obesity rates increased with age and reached 22.4% for men and 40.4%
      for women aged 55-64 years. Lower education was associated with higher obesity
      rates, with lowest rates observed for Jewish women with an academic education
      (13.6%) and highest rates observed for Arab women with a basic education (57.3%).
      Multiple logistic regression analyses showed age to be a significant risk factor
      in men. Age, education and origin (Arab, and the former Soviet Union for Jews)
      were significant risk factors for obesity in women. CONCLUSIONS: Obesity rates in
      Israel are high and comparable to those in the United States. Of special concern
      is the subgroup of older Arab women (55-64 years), whose obesity rates reached
      70%.

PMID- 15847201
TI  - No gender difference in the clinical management and outcome of unstable angina.
AB  - BACKGROUND: Women with myocardial infarction have a less favorable prognosis than
      men. Many studies have indicated gender bias in the evaluation and treatment of
      myocardial infarction, but few data exist concerning these aspects in the
      management of unstable angina. OBJECTIVE: To investigate gender differences in
      the baseline characteristics, clinical presentation, treatment and prognosis of
      women with unstable angina. METHOD: Data were collected prospectively as part of
      the Acute Coronary Syndromes Israeli Survey in 2000 at Soroka University Medical
      Center. In-hospital management and 2 year follow-up were monitored for 226
      consecutive patients with unstable angina admitted to our medical center during
      February and March 2000. RESULTS: Women were older (71 +/- 12 vs. 66 +/- 12, P =
      0.006), more diabetic (41.3% vs. 34.5%, not significant) and hypertensive (76.3%
      vs. 64.6%, P = 0.07). Women presented more often with atypical chest pain (18.8%
      vs. 7.5%, P = 0.038). Heparin, aspirin and angiotensin-converting enzyme
      inhibitor were delivered equally, but more beta-blockers were administered to
      women (88.5% vs. 75.7%, P = 0.02) and more statins to men (48.1% vs. 35.4%, P =
      0.07). Angiography rates were similar (17.7% vs. 19.6%). Similar management was
      documented during the 2 year follow-up. Re-hospitalization rates were similar
      (53.3% of women and 63.7% of men, NS). Men had a tendency to develop acute
      myocardial infarction more often (9.6% vs. 2.7%, P = 0.06) and to develop
      peripheral vascular disease (3.7% vs. 0%, P = 0.09), and they had a non
      significant higher rate of coronary artery bypass graft (6.7% vs. 1.3%, P =
      0.08). No gender difference was found in angiography (14.7% of women vs. 16.3% of
      men) or percutaneous intervention (13% vs. 16.7%). At 2 years there was no gender
      related difference in mortality (13.3% of women vs. 16.3% of , NS). Kaplan-Meier
      analysis for event-free survival after 2 years showed no gender difference in
      survival. Multi-regression analysis showed that gender was not a prognostic
      factor for survival. CONCLUSIONS: We found no major difference in the management
      of men and women with unstable angina. Although men showed a tendency to suffer
      more major cardiac events, their 2 year prognosis was the same as for women.

PMID- 15847202
TI  - Small artery compliance in cirrhotic patients during total paracentes.
AB  - BACKGROUND: Hemodynamic changes, including systemic vascular resistance, in
      cirrhotic patients during massive paracentesis have been reported, but large and
      small artery compliance has not yet been investigated. OBJECTIVE: To investigate
      hemodynamic variables, including small and large artery compliance, in cirrhotic
      patients during total paracentesis. METHODS: The study included 15 cirrhotic
      patients admitted for an episode of tense diuretic-resistant ascites. Hemodynamic
      variables including vascular compliance were measured using an HDI pulse wave
      cardiovascular profiling instrument CR-2000. The variables were measured in these
      patients before, immediately after, and 24 hours following large volume (mean 5.6
      L) paracentesis. RESULTS: Cardiac output increased immediately after paracentesis
      due to increment in stroke volume, with no change in heart rate. However, 24
      hours later the cardiac output decreased to below the basal level. The
      fluctuation was statistically significant (P < 0.05). There was no change in
      large artery compliance, but small artery compliance increased after paracentesis
      (P < 0.05) and partially retumed to the basal level after 24 hours. Systemic
      vascular resistance measurement showed the same pattern of change: vasodilatation
      occurred during paracentesis and was attenuated 24 hours later. CONCLUSIONS:
      Large volume paracentesis with albumin replacement caused an accentuation of the
      vasodilatation (small but not large artery) already present in these patients.
      This may be the first sign of enhanced vasodilatation due to large volume
      paracentesis before the clinical expression of impaired hemodynamics and
      deterioration of renal function.

PMID- 15847203
TI  - Congenital cytomegalovirus infection in Israel: screening in different
      subpopulations.
AB  - BACKGROUND: The incidence of congenital cytomegalovirus in Israel has never been
      determined, either in general or in relation to various population subgroups. We
      recently proved the utility of newborn urine polymerase chain reaction as a
      screening tool for congenital CMV. OBJECTIVES: To define the incidence of
      congenital CMV infection in two different subpopulations, as a model for the
      entire population of Israel. METHODS: Urine specimens were randomly collected
      from 2,000 newborns in Shaare Zedek Medical Center, Jerusalem, and HaEmek Medical
      Center, Afula (1,000 specimens each). These hospitals have many characteristic
      differences, presumably representing the diverse population of Israel. Urine
      specimens were subjected to a CMV PCR reaction and positive specimens were
      validated by urine viral culture. Maternal seroprevalence was determined in a
      representative sample of the mothers in each hospital. Epidemiologic
      characteristics of the mothers were extracted from hospital records and compared.
      RESULTS: The population in Shaare Zedek Medical Center was mostly Jewish (97.7%)
      and urban (87.0%), as compared to that of HaEmek Medical Center (49.2% and 61.0%,
      respectively, P < 0.01). Nevertheless, CMV seroprevalence was similar: 81.5% and
      85%, respectively. Ten (1.0%) and 4 (0.4%) newborns, respectively, were found to
      have congenital CMV infection (not significant). CONCLUSIONS: The combined
      incidence of congenital CMV infection in the study population was 0.7% (95%
      confidence interval 0.3-1.0%). If this rate is extrapolated to the entire
      population of Israel, then a total of 945 cases of congenital CMV can be expected
      among the 135,000 annual deliveries. A nationwide screening program for
      congenital CMV should be considered.

PMID- 15847204
TI  - Pharyngotonsillitis due to Arcanobacterium haemolyticum in northern Israel.
AB  - BACKGROUND: Arcanobacterium haemolyticum is a well-recognized but uncommon cause
      of pharyngitis and skin rash in adolescents and young adults. To date, no data
      regarding its frequency in Israel have been published. OBJECTIVE: To establish
      the frequency of A. haemolyticum in throat cultures in a northern Israeli
      population and to estimate the clinical significance of this pathogen in patients
      with sore throat. METHODS: We examined suspected colonies for A haemolyticum by
      gram stain, catalase test and reverse CAMP test in 518 throat cultures sent to
      the microbiologic laboratory of HaEmek Medical Center. RESULTS: Of the throat
      cultures tested, A. haemolyticum was recovered from one patient (0.2%). In
      contrast, group A Streptococcus (Streptococcus pyogenes) was recovered from 135
      patients (26%). CONCLUSION: A hemolyticum is an uncommon pathogen implicated in
      acute pharyngitis, therefore routine screening in throat swabs is not required.

PMID- 15847205
TI  - The use of complementary and alternative therapies by cancer patients in northern
      Israel.
AB  - BACKGROUND: The use of complementary and alternative medicine has increased over
      the last decade in the western world. OBJECTIVES: To evaluate the extent and
      characteristics of CAM use among cancer patients in northern Israel. METHODS:
      Telephone interviews were conducted with 2,176 newly registered cancer patients
      or their family members, at least 1 year following referral. RESULTS: The rates
      of CAM use varied significantly according to demographic characteristics and
      chemotherapy treatment, from 3% in the basically educated elderly group up to 69%
      of educated Israeli-born Jews younger than 70 years receiving chemotherapy. The
      overall rate of CAM use was 17%. The most influential factors determining CAM use
      were academic or high school education, chemotherapy treatment, Israel as country
      of birth, and age 41-50 years. All patients used CAM in addition to conventional
      therapies. Less than half of them reported it to their physicians. The most
      frequently used treatments were various chemical, biological, botanic and
      homeopathy remedies. Friends and relatives were the main recommenders of CAM.
      Most CAM users reported that they used CAM because they believed it "strengthens
      the immune system," alleviates side effects of chemotherapy, improves quality of
      life, and helps to overcome pain and stress; 62% of them reported subjective
      beneficial effects. CONCLUSIONS: A predicting module of CAM user patients was
      built that may help physicians initiate conversations with their patients on CAM
      use. Expanding physicians' knowledge on CAM methods will encourage them to
      provide additional advice, promote the use of beneficial therapies, and inform
      patients about potentially harmful methods.

PMID- 15847206
TI  - Strategy for colorectal cancer screening.
AB  - Colorectal cancer is a leading cause of cancer death in Israel. Our current
      understanding of the colorectal adenoma-carcinoma sequence has led to the use of
      screening for timely detection of polyps and cancer. Digital examination of the
      rectum is a test that can be performed by all doctors. Fecal occult blood
      testing, flexible sigmoidoscopy and colonoscopy are the standard screening
      techniques for patients. Computerized tomography colonography is now entering
      this field. This review discusses the merits and uncertainties of these
      strategies as related to the risk of colorectal cancer in selected populations.

PMID- 15847207
TI  - Cardiovascular disease prevention and treatment in patients with human
      immunodeficiency virus.
AB  - Highly active antiretroviral therapy has dramatically improved the quality of
      life and life expectancy of patients with human immunodeficiency virus. However,
      the prolonged use of HAART leads to severe metabolic adverse events. Both HIV
      infection and HAART can cause changes in lipid and glucose metabolism as well as
      elevation of blood pressure, promoting the development of atherosclerosis.
      Cardiovascular diseases have become a major cause of mortality among HIV-infected
      subjects who respond well to antiretroviral therapy. Nevertheless, a proper
      lifestyle and pharmacologic intervention can improve cardiovascular risk factors
      in the HIV-treated population and significantly reduce healthcare investments in
      the treatment of future cardiovascular complications in this population. In this
      review we summarize the current knowledge of CVD prevention and treatment in HIV
      patients.

PMID- 15847208
TI  - The emerging role of the new aromatase inhibitors in the treatment of breast
      cancer.
AB  - The clinical development of aromatase inhibitors in recent years represents a
      significant addition to our armamentarium for the treatment of postmenopausal
      patients with hormone receptor-positive breast cancer--both for metastatic
      disease and in the adjuvant setting. In patients with metastatic disease, third
      generation aromatase inhibitors have shown significantly superior efficacy over
      tamoxifen as first-line hormone therapy. In the adjuvant setting, preliminary
      results with the use of aromatase inhibitors in ongoing large clinical trials
      indicate significant gains in disease-free survival rates and in the occurrence
      of contralateral breast cancer, either alone for 5 years or sequentially after
      tamoxifen for 2-3 or 5 years. While tamoxifen monotherapy continues to be
      standard adjuvant therapy for patients with low risk primary breast cancer,
      postmenopausal patients with higher risk hormone-positive primary breast cancer
      should also be offered an aromatase inhibitor. Aromatase inhibitors are also
      prescribed for patients with contraindications to tamoxifen. The optimal sequence
      and duration of aromatase inhibitor adjuvant therapy as well as its long-term
      impact on overall survival remain to be established. In general, aromatase
      inhibitors have a good toxicity profile. Long-term effects such as the risk of
      osteoporosis need to be better defined.

PMID- 15847209
TI  - Capsule endoscopy in Crohn's disease.

PMID- 15847210
TI  - Autoimmune hepatitis: a part of the antiphospholipid syndrome?

PMID- 15847211
TI  - Cyclophosphamide restores heart function in a patient with lupus myocarditis.

PMID- 15847212
TI  - Antiphospholipid antibody syndrome in autoimmune hepatitis.

PMID- 15847213
TI  - Medial rectus muscle injury complicating functional endoscopic sinus surgery.

PMID- 15847214
TI  - Congenital isolated pleural effusion associated with obstructive uropathy.

PMID- 15847215
TI  - LEMD3: the gene responsible for bone density disorders (osteopoikilosis).

PMID- 15847216
TI  - Assessment of coronary artery bypass grafts by cardiac computed tomography
      angiography.

PMID- 15847217
TI  - Successful percutaneous embolization of a renal arteriovenous fistula following
      renal biopsy.

PMID- 15847218
TI  - Emphysematous complications in dentistry.

PMID- 15847219
TI  - Are fleet enemas safe?

PMID- 15847220
TI  - [Susceptibility of ESBL-producing Escherichia coli and Klebsiella pneumoniae to
      various antibacterial agents].
AB  - With the increasing use of broad-spectrum antibacterial agents, the increase in
      various drug-resistant bacterial strains has become a concern in recent years.
      Especially, the development of drug-resistance by Enterobacteriaceae which
      significantly affects therapy and prognosis in sepsis and lower gastrointestinal
      post-operative infection. The extended spectrum beta-lactamase (ESBL)-producing
      Enterobacteriaceae strains isolated in the Surveillance Program of Bacterial
      Resistance in Kinki region of Japan (SBRK) were supplied between November 2000
      and March 2003. The susceptibilities of them to 16 kinds of antimicrobial agents
      were investigated. The number of them was 48 strains consisting of 36 Escherichia
      coli strains (75%) and 12 Klebsiella pneumoniae strains (25%). Our focus was on
      carbapenem and the new quinolone antibacterial agents. Among the 16 major
      antibacterial agents examined, carbapenem had low MIC50/90 values. Meropenem had
      a MIC50/90 of 0.03/0.06microg/ml, followed by biapenem (0.12/0.5), imipenem
      (0.25/0.5) and panipenem (0.25/0.5). Among cephem, ceftazidime had the lowest
      MIC50 at 4 microg/ml. All four of the cephem agents had a MIC90 of greater than
      128microg/ml. Among beta-lactamase inhibitors, tazobactam/piperacillin had the
      lowest MIC50 at 4 microg/ml, and sulbactam/cefoperazone had a MIC50 of 32
      microg/ml. Among the new quinolones, prulifloxacin had the lowest MIC50 at 1
      microg/ml, and the other drugs had a MIC50 of 2 microg/ml. The resistance rate of
      ciprofloxacin was 61.1% in E. coli and 16.6% in K. pneumoniae. Comparison of drug
      sensitivity to cephem by ESBL-gene type revealed that cefpirome, cefepime and
      cefozopran had higher MIC50/90 values against the CTX-M group with a MIC50 of
      greater than 128microg/ml. Ceftazidime and aztreonam had higher MIC50/90 values
      against the TEM/SHV group than those against the CTX-M group. In the CTX-M group,
      the MIC50 was 4 and 16microg/ml, respectively.

PMID- 15847221
TI  - [Combination effect of pazufloxacin and anti-mrsa drugs against beta-lactam
      antibiotic induced vancomycin-resistant MRSA (BIVR)].
AB  - The in vitro combination effects of pazufloxacin (PZFX) with an anti-MRSA drug
      such as vancomycin (VCM), teicoplanin (TEIC), arbekacin (ABK), minocycline
      (MINO), rifampicin (RFP) and sulfamethoxazole-trimethoprim (ST) were investigated
      against 26 strains of beta-lactam antibiotic induced vancomycin-resistant MRSA
      (BIVR) by the checkerboard method. The additive and synergistic effects were
      observed with the combination of PZFX and VCM (50%, 13/26 strains), PZFX and TEIC
      (96%, 25/26 strains), PZFX and ABK (65%, 17/26 strains), PZFX and MINO (46%,
      12/26 strains), PZFX and ST (54%, 14/26 strains). The synergistic effects were
      observed with the combination of PZFX and TEIC (4%, 1/26 strains), PZFX and ABK
      or MINO (15%, 4/26 strains). The antagonistic effects were observed with only
      PZFX and MINO (12%, 3/26 strains), others were all indifference.

PMID- 15847222
TI  - [Antimicrobial susceptibility surveillance of recent isolates from
      ophthalmological infections to gatifloxacin and other antimicrobial drugs].
AB  - The antimicrobial susceptibility of 240 isolates from the ophthalmological
      infections during July 2003 to March 2004 was determined to gatifloxacin (GFLX),
      levofloxacin, lomefloxacin and cefmenoxime applicable for ophthalmological
      infections. The in vitro activities of these drugs against the fresh isolates
      were compared. The quinolones including GFLX were potently active against Gram
      positive bacteria, except for MRSA, a major causative pathogens for
      ophthalmological infection. When MIC ranges, MIC50 and MIC90 of three quinolones
      were compared, it was considered that the activity of GFLX was the most active of
      them. GFLX showed to be more active against opportunistic pathogens including
      Pseudomonas aeruginosa than other antimicrobial agents, and GFLX was especially
      potent against Streptococcus pneumoniae and Enterococcus faecalis. In conclusion,
      GFLX exhibits a potently active against fresh isolates from ophthalmological
      infections, and has an effective potential in the treatment of ophthalmological
      infections with the drug to administer eye drops.

PMID- 15847223
TI  - [Studies on biosynthetic genes and enzymes of isoprenoids produced by
      actinomycetes].

PMID- 15847224
TI  - [HIV-1 polymorphism and development of resistance mutations against non
      nucleoside reverse transcriptase inhibitor, efavirenz].

PMID- 15847225
TI  - Calendar and reverse calendar effects: time peaks in memory as a function of
      temporal cues.
AB  - Prior research on autobiographical memory revealed that students typically report
      more memories from semester boundaries than from other times. Explanations for
      these calendar effects were examined in two experiments. In Experiment 1,
      temporal cues were eliminated from the memory cueing task, and an opposite
      outcome obtained: a greater amount of memories per week in the middle of
      semesters than at the boundaries (a reverse calendar effect). Experiment 2
      replicated and extended this finding by including conditions with temporal cues
      at different points in the instructions: pre-retrieval or post-retrieval. In the
      no-cue condition, the reverse calendar effect was replicated. The calendar effect
      was evident in both cue conditions, but to a greater degree in the pre-retrieval
      group. These findings contradict encoding explanations of the calendar effect and
      are best explained by a combination of anchoring bias and temporal landmarks.

PMID- 15847226
TI  - The mental representation of living and nonliving things: differential weighting
      and interactivity of sensorial and non-sensorial features.
AB  - Warrington and colleagues (Warrington & McCarthy, 1983, 1987; Warrington &
      Shallice, 1984) claimed that sensorial and functional-associative (FA) features
      are differentially important in determining the meaning of living things (LT) and
      nonliving things (NLT). The first aim of the present study was to evaluate this
      hypothesis through two different access tasks: feature generation (Experiment 1)
      and cued recall (Experiment 2). The results of both experiments provided
      consistent empirical support for Warrington and colleagues' assumption. The
      second aim of the present study was to test a new differential interactivity
      hypothesis that combines Warrington and colleagueS' assumption with the notion of
      a higher number of intercorrelations and hence of a stronger connectivity between
      sensorial and non-sensorial features for LTs than for NLTs. This hypothesis was
      motivated by previoUs reports of an uncrossed interaction between domain (LTs vs
      NLTs) and attribute type (sensorial vs FA) in, for example, a feature
      verification task (Laws, Humber, Ramsey, & McCarthy, 1995): while FA attributes
      are verified faster than sensorial attributes for NLTs, no difference is observed
      for LTs. We replicated and generalised this finding using several feature
      verification tasks on both written words and pictures (Experiment 3), including
      in conditions aimed at minimising the intervention of priming biases and
      strategic or mnemonic processes (Experiment 4). The whole set of results suggests
      that both privileged relations between features and categories, and the
      differential importance of intercorrelations between features as a function of
      category, modulate access to semantic features.

PMID- 15847227
TI  - Selective effects of emotion on the phenomenal characteristics of
      autobiographical memories.
AB  - The present study investigates the emotional determinants of the phenomenal
      characteristics of autobiographical memories. A total of 84 participants
      completed the Memory Characteristics Questionnaire (MCQ, Johnson, Foley, Suengas,
      & Raye, 1988) after retrieving and orally describing a negative, a positive, and
      a neutral autobiographical memory. In addition, self-report and physiological
      measures of emotional state at retrieval were recorded. Results suggest that
      recall of perceptual, sensory, and semantic elements is better for emotional
      memories than for neutral ones. This difference is not significant for contextual
      and temporal aspects, suggesting that emotional memories are more vivid but no
      more specific than are neutral ones. In addition, positive memories yielded
      higher MCQ ratings than did negative memories for sensory, temporal, and
      contextual aspects. Finally, correlations suggest a positive relation between
      emotional state at retrieval and level of phenomenal detail of retrieved
      memories. Results are interpreted in terms of multilevel models of emotion and of
      Conway and Pleydell-Pearce's (2000) model.

PMID- 15847228
TI  - The wane of childhood amnesia for autobiographical and public event memories.
AB  - We modified Bruce, Dolan, and Phillips-Grant's (2000) threshold procedure for
      determining the wane of childhood amnesia. In two experiments, undergraduates
      labelled childhood events (e.g., your first permanent tooth came in) as know or
      recollect memories and estimated their age at the event's occurrence. In both
      studies the estimated transition from mostly know memories to mostly recollect
      memories was roughly 4.7 years. This transition estimate was replicated in a
      sample of adults (ages 24-65 years) with both Bruce et al.'s event-generation
      task and the Experiment 1a questionnaire. By contrast, in two experiments a
      transition estimate of roughly 6 years was found for undergraduates' memories of
      public events (e.g., the Challenger explosion). The wane of childhood amnesia
      appears to occur around 4.7 years.

PMID- 15847229
TI  - Representation of plans: activation in memory.
AB  - The purpose of this study is to examine the temporal representation of plans in
      memory. Two experiments using a priming paradigm were conducted to investigate
      which plans would be activated in memory when participants processed a particular
      plan. The 64 undergraduates who participated in Experiment 1 were asked to
      memorise a 1-month schedule of plans. Results showed that when participants were
      presented with a particular plan as a prime, the preceding plan in the schedule
      was immediately activated. After the activation of the preceding plan, the plan
      following the prime plan in the schedule was activated. Experiment 2 was
      conducted to examine whether the sequential effect found in Experiment 1 might be
      based on day order (e.g., plans for day 1, plans for day 2, etc.) or simple
      ordering of plans (e.g., plan 1, plan 2, etc.). However, in the results of
      Experiment 2, with 48 undergraduate participants, the dynamic transition in the
      activation of plans along the time course, seen in Experiment 1, was not
      observed.

PMID- 15847230
TI  - Using cumulative-recall curves to assess the extent of relational and item
      specific processing.
AB  - Although distinguishing between item-specific and relational information has
      proved to be a useful approach for understanding a variety of important memory
      phenomena, finding measurement tools for assessing the amount and type of
      information processed has proven difficult. Using the repeated-testing procedure,
      Burns (1993) demonstrated that item gains (the recall of items on a later test
      that were not recalled on earlier tests) and item losses (the forgetting of items
      on a later test that were recalled on earlier tests) reflected differences in
      amount of item-specific and relational information processed, respectively.
      Although several researchers have begun to use the measures with apparent
      success, the present research demonstrates that the accuracy of the item-gain
      measure is largely dependent on the rather arbitrary choice of recall-test
      length. We also show that a related but alternative measure, analysis of
      cumulative-recall curves, avoids some of the shortcomings of the item gain and
      loss measures. Moreover, we provide evidence for the generality of the cumulative
      recall approach by demonstrating its effectiveness in mixed-list designs.

PMID- 15847231
TI  - Another look at retroactive and proactive interference: a quantitative analysis
      of conversion processes.
AB  - Traditionally, the causes of interference phenomena were sought in "real" or
      "hard" memory processes such as unlearning, response competition, or inhibition,
      which serve to reduce the accessibility of target items. I propose an alternative
      approach which does not deny the influence of such processes but highlights a
      second, equally important, source of interference-the conversion (Tulving, 1983)
      of accessible memory information into memory performance. Conversion is conceived
      as a problem-solving-like activity in which the rememberer tries to find
      solutions to a memory task. Conversion-based interference effects are traced to
      different conversion processes in the experimental and control conditions of
      interference designs. I present a simple theoretical model that quantitatively
      predicts the resulting amount of interference. In two paired-associate learning
      experiments using two different types of memory tests, these predictions were
      corroborated. Relations of the present approach to traditional accounts of
      interference phenomena and implications for eyewitness testimony are discussed.

PMID- 15847232
TI  - The uninsured: a forgotten population.

PMID- 15847233
TI  - Stability of health care coverage among low-income working women.
AB  - This article examines health insurance stability patterns and the factors
      associated with stable coverage in a sample of 453 low-income working women.
      Using data from the National Longitudinal Survey of Youth (NLSY), the authors
      found that only 51 percent of these women had stable coverage during 1995-1997.
      Logistic regression results indicate that, controlling for other factors, health
      insurance stability is significantly higher for those who have higher levels of
      welfare receipt, have more work hours, have fewer job changes, have higher
      education levels, are African American or Hispanic, and who live outside central
      cities. The findings suggest that point-in-time health coverage estimates
      substantially underestimate the health coverage problems of low-income working
      women. Health policies need to be more sensitive to transitional problems
      resulting from job changes, marital disruptions, and other changes in
      circumstances. Recommendations for revising health care policies and for
      improving existing health care programs are presented.

PMID- 15847234
TI  - Transgender health: findings from two needs assessment studies in Philadelphia.
AB  - HIV/AIDS, suicide, violence, and barriers to health care access among transgender
      people were explored using two needs assessment surveys conducted in Philadelphia
      in 1997. A total of 182 people responded to a face-to-face interview or self
      administered mail survey: 113 male-to-female individuals and 69 female-to-male
      individuals. About three-fifths of respondents had engaged in unprotected sexual
      activity during the past 12 months. The risk for HIV infection from unprotected
      sex was significantly higher among respondents of color than among white
      respondents. About one-third (30.1 percent) of respondents had attempted suicide.
      More than half of respondents had been forced to have sex, 56.3 percent had
      experienced violence in their homes, and 51.3 percent had been physically abused.
      Twenty-six percent of respondents had been denied medical care because they were
      transgender. These findings suggest that prevention services that specifically
      address HIV/AIDS, suicide, and violence among transgender people are urgently
      needed.

PMID- 15847235
TI  - Assessment and the ubiquity of culture: threats to validity in measures of health
      related quality of life.
AB  - Social workers in health care settings are increasingly using patient-based
      assessments (PBAs) of health-related quality of life such as the SF-36. However,
      the validity of many PBAs for use with cultural minority groups is limited. To
      ensure that cultural minority groups are not misrepresented by standardized
      measures, social workers--as effective patient advocates--must be familiar with
      the underlying conceptual assumptions of measurement theory to articulate the
      strengths and limitations of measures used to investigate populations with which
      they have not been tested and advocate for cultural minority groups using
      language and terminology that measurement practitioners can understand and
      embrace.

PMID- 15847236
TI  - High-risk pregnancy and hospitalization: the women's voices.
AB  - The study is a phenomenological analysis of 10 focus groups with Israeli women
      who were hospitalized because of high-risk pregnancy. The goal of this study was
      to understand the lived experience of hospitalization due to high-risk pregnancy.
      Five themes were recognized: (1) the desire to nurture and the social pressure to
      do so; (2) the personal and social meaning of a family; (3) loss of normal
      experiences of life and childbearing; (4) the woman's needs versus the fetus's
      well-being; and (5) sources of strength and stress. Conflicting relationships
      recognized within and between the themes pointed to ambivalence as the core
      characteristic of the experience. Practical implications and further research are
      recommended to better inform health care personnel and social workers assisting
      these women.

PMID- 15847237
TI  - Challenges in the new prospective payment system: action steps for social work in
      home health care.
AB  - The Balanced Budget Act of 1997 changed the reimbursement rules for Medicare home
      health benefits from a fee-for-service system to a prospective payment system
      (PPS). As with Medicare's hospital reimbursement system, home health agencies
      have to provide appropriate and adequate care for a flat rate reimbursement for
      each patient. As a result coordination and collaboration among all members of the
      home health care team (that is, nurses, social workers, physical therapist,
      occupational therapist, speech therapist, and home health aides) is critical to
      provide home care for frail and chronically ill populations. The authors provide
      background on the PPS, home health care, and social work roles in home health
      care and propose policy and research action steps for the social work profession.

PMID- 15847238
TI  - Women, mental health, and the psychiatric enterprise: a review.
AB  - This article raises questions about how social workers can be more responsive to
      the needs and wants of women who struggle with mental, emotional, and behavioral
      disorders. Specifically, the article examines the history and theoretical context
      of mental health services for women, reviews lessons learned from women's own
      descriptions of their lived experiences with mental illness, and summarizes
      needed responses to the treatment needs of women. Recommendations are offered in
      areas of the general structure of the service delivery system, psychosocial and
      psychotherapeutic interventions, and psychopharmacology.

PMID- 15847239
TI  - The lion at the gate: an HIV-affected caregiver resists stigma.
AB  - This article examines two bounded stories of HIV stigma told by an older woman
      who took care of her adult son as he died of AIDS. Her self-definition as a
      protector of her dying son was challenged when she encountered ostracism and
      prejudice. Her words and expressions illuminate her confrontation and resistance
      to associative stigma. An expansion of Goffman's view of stigma management is
      necessary to understand this caregiver's experiences in the face of the larger
      cultural narrative of HIV stigma:This caregiver did not manage stigma, she
      actively fought it.

PMID- 15847240
TI  - Let's not gamble with social security.

PMID- 15847241
TI  - The use of traditional Chinese culture and values in social work health care
      related interventions in Hong Kong.

PMID- 15847242
TI  - The association between weight fluctuation and mortality: results from a
      population-based cohort study.
AB  - Previous studies evaluating the association between weight fluctuation and
      mortality are limited and have conflicting results. This study will further
      evaluate the association between weight fluctuation and mortality in a nationally
      representative cohort by performing survival analysis of NHANES I and NHANES I
      Epidemiologic Follow-up Study (n = 8479; weighted sample = 68,200,905). This
      cohort was followed from 1971 to 1992 and categorized using weight change over
      five time points into stable non-obese, stable obese, weight gain, weight loss
      and weight fluctuation groups. All-cause mortality (ACM) and cardiovascular
      mortality (CM) were evaluated. Respondents with weight fluctuation had higher ACM
      (HR: 1.83, 95% CI: 1.25-2.69) and CM hazards ratios (HR: 1.86, 95% CI: 1.10-3.15)
      than the stable non-obese group, even after controlling for pre-existing disease,
      initial BMI and excluding those in poor health or incapacitated. Increased
      mortality was also seen in the weight loss group (ACM HR: 3.36, 95% CI: 2.47
      4.55), (CM HR 4.22, 95% CI: 2.60-6.84). The stable obese group did not have
      increased ACM, but did have increased CM prior to the exclusion of those in poor
      health or incapacitated. (HR: 2.17, 95% CI: 1.10-4.28). Weight fluctuation is
      associated with a higher risk of all-cause and cardiovascular disease mortality
      in the US population, even after adjustment for pre-existing disease, initial BMI
      and the exclusion of those in poor health or incapacitated. Thus, health care
      providers should promote a commitment to maintaining weight loss to avoid weight
      fluctuation and consider patients' weight histories when assessing their risk
      status.

PMID- 15847243
TI  - Strategies to recruit and retain older Filipino-American immigrants for a cancer
      screening study.
AB  - Recruitment and retention of subjects in cancer prevention, screening, and
      treatment trials is challenging, especially if subjects are low-income, from
      minority groups or immigrants with limited English fluency. This article
      describes our experiences in recruiting 530 female Filipino-American immigrants
      at community based organizations and churches for a randomized trial that
      assessed the effect of a small group educational session on breast and cervical
      cancer screening. We found that a personal invitation from either a female
      project liaison, a friend, or the Filipino project director were all successful
      strategies that resulted in over 80% attendance at an educational session that
      was offered as part of the study. Although non-attendees did not differ from
      attendees in demographic characteristics, they expressed significantly more
      barriers to participating in a health study. Attendance at the group session was
      a significant predictor of retention in the study. We were able to conduct
      telephone follow-up surveys among 88% of enrollees at 12 month follow-up and 76%
      at 24 month follow-up. Results and implications are discussed in the hope that
      they may facilitate future participation of Filipinos and other Asian immigrants
      in research.

PMID- 15847244
TI  - Employment and health insurance coverage for rural Latino populations.
AB  - Rural Latino populations continue to grow in part due to relocation of food
      processing industries to rural America along with other manufacturing and large
      retail stores. We use data from the Current Population Survey to examine the
      labor force participation of rural Latino population and the role rural employers
      play in providing health insurance coverage. We found that while rural Latinos
      are more likely to be uninsured, the meat packing industry has higher health
      insurance coverage rates than other rural employers such as construction and
      retail. Local communities recruiting new businesses to their rural communities
      need to explore the role that employers will play in providing health insurance
      coverage. Lack of adequate coverage will have an impact on the income, resources,
      and day-to-day activities of physicians, hospitals and traditional safety net
      providers.

PMID- 15847245
TI  - Needs assessment of rural communities: a focus on older adults.
AB  - High-quality community needs assessments can help focus limited resources on the
      needs of a rapidly expanding population-older Americans. Based on such
      assessments, organizations and communities can effectively plan and deliver cost
      effective, appropriate health promotion/wellness programs and health/social
      services to targeted populations. This article, which describes the Arkansas
      Aging Initiative's (AAI) use of a community needs assessment to identify its
      constituents' top health needs, provides specific background information for
      communities with demographics similar to those in Arkansas and offers assessment
      strategies for communities throughout the US. The AAI used two complementary
      methodologies to obtain critical input from Arkansas providers and their
      communities: focus groups of healthcare providers and community members and
      surveys administered to older adults. The assessment confirmed that health
      problems in the communities were consistent with leading causes of morbidity and
      mortality at state and national levels. It indicated that respondents' top three
      health needs related to affordability, including affordability of prescription
      medications, medical care, and health insurance, and that needs varied inversely
      with age. In other findings, married individuals rated their own health as better
      than their single counterparts; whites rated their health better than non-whites;
      and more than half of respondents reported leaving their counties to receive
      healthcare. This community needs assessment has enabled the AAI to address
      respondents' needs by developing specific educational and interdisciplinary
      healthcare initiatives, such as increasing access to a prescription drug
      assistance program.

PMID- 15847246
TI  - Evaluation of literacy level of patient education pages in health-related
      journals.
AB  - The purpose of this study was to evaluate the reading level of patient education
      material from selected current health care journals. Ten patient education pages
      from a variety of health care journals were entered into a Microsoft Word
      program. Applying the Flesch-Kincaid readability formula available from Microsoft
      Word, a reading level for each page was established and compared to recommended
      standards. Only 2 of 10 patient education pages fell within the recommended
      reading levels for health-related materials, and 5 of 10 were above the estimated
      mean U.S. reading level of 8th grade. A 5th to 6th grade level is recommended for
      patient education materials. This study suggests that although it is known that
      low health literacy is a widespread problem, it is not always considered when
      patient-targeted materials are developed. Health care professionals need to
      become more active in addressing the literacy needs of the intended receiver of
      written health-related information.

PMID- 15847247
TI  - How do we determine whether community health workers are cost-effective? Some
      core methodological issues.
AB  - Since the Alma-Ata Conference in 1978 reiterated the goal of "Health for All by
      the Year 2000", health service delivery programs promoting the primary health
      care approach using community health workers (CHWs) have been established in many
      developing countries. These programs are expected to improve the cost
      effectiveness of health care systems by reaching large numbers of previously
      underserved people with high-impact basic services at low cost. However, there is
      a dearth of data on the cost-effectiveness of CHW programs to confirm these
      views. This may be because conventional approaches to economic evaluation,
      particularly cost-effectiveness, tend not to capture the institutional features
      of CHW programs. Therefore, this paper aims to examine the means by which
      economic methods can be extended to provide evidence regarding the cost
      effectiveness of CHWs in developing countries.

PMID- 15847248
TI  - Progress towards poliomyelitis eradication in Afghanistan and Pakistan, January
      2004 to February 2005.

PMID- 15847249
TI  - Acute inflammation in peritoneal dialysis: experimental studies in rats.
      Characterization of regulatory mechanisms.
AB  - The predominant problems associated with peritoneal dialysis (PD) are
      ultrafiltration failure and peritonitis. PD maintains a state of intraperitoneal
      inflammation that affects the structure and function of the peritoneal membrane,
      potentially impairing ultrafiltration efficiency. Paradoxically, some PD fluids
      also have anti-inflammatory properties that may compromise the immune defense
      against peritonitis. This anti-inflammatory feature is mostly due to the glucose
      degradation products (GDPs), formed during heat-sterilization and storage of PD
      fluids. The main purpose of the present thesis was to study regulatory mechanisms
      behind the acute intraperitoneal inflammatory response in PD in the presence and
      absence of experimental peritonitis. Rats were exposed to a single dose of heat-
      or filter sterilized PD fluids either as an i.p. injection or as an infusion
      through an indwelling catheter, with or without supplementations, or pretreatment
      of the animals. The dwell fluid was analyzed zero, two and four hours later
      concerning activation of the complement and coagulation cascades, neutrophil
      recruitment and respiratory burst, ultrafiltration volumes, cytokine-induced
      neutrophil chemoattractant (CINC-1), rat mast cell protease 2 (RMCP-2), glucose,
      urea and histamine concentrations and ex vivo/in vitro intraperitoneal
      chemotactic activity. Exposure to filter sterilized PD fluid alone induced
      intraperitoneal complement activation and coagulation, neutrophil recruitment and
      increased the levels of CINC-1 during the dwell. Intraperitoneal concentrations
      of the mast cell markers histamine and RMCP-2 changed little during the dwells
      and did not indicate mast cell activation. Low molecular weight heparin (LMWH)
      and C5 blockade improved ultrafiltration. Pretreatment with cobra venom factor,
      known decomplementing agent, blocked the CINC-1 release and the neutrophil
      recruitment and improved ultrafiltration. In combination with experimental
      peritonitis, heat sterilized PD fluid compared to filter sterilized, inhibited
      the CINC-1 release and the recruitment of neutrophils to the peritoneal cavity
      without affecting the intraperitoneal complement activation. The results of the
      present thesis indicate that addition of LMWH to the PD fluid improves
      ultrafiltration, probably by blocking C5a activity. C5 blockade seems to improve
      ultrafiltration by a mechanism that involves a reduction in glucose transport,
      possibly by reducing C5 induced vasodilatation. Complement activation is an early
      step in the acute reaction to PD and probably mediates the downstream events that
      lead to the recruitment of inflammatory cells to the peritoneal cavity. The cells
      involved in the release of CINC-1 later in this sequence are probably the
      mesothelial cells. During experimental peritonitis, heat sterilized PD fluids
      inhibited the neutrophil respiratory burst response of intraperitoneal
      neutrophils. Heat sterilized PD fluids also inhibit the recruitment of
      neutrophils to the peritoneal cavity by a mechanism independent of complement
      activation but probably depending on cytokine CINC-1 release during peritonitis.

PMID- 15847250
TI  - The acute effect of atorvastatin on proteinuria in patients with chronic
      glomerulonephritis.
AB  - BACKGROUND: Hyperlipidemia may develop early in the course of renal disease, and
      statin treatment to lower lipid levels in these patients is effective. In
      addition, it has been suggested that proteinuria may decrease after prolonged
      periods of statin treatment. In the present study, we set out to evaluate the
      short-term effect of atorvastatin after only six weeks of therapy. MATERIAL AND
      METHODS: Plasma albumin, creatinine, creatinine clearance, proteinuria and lipid
      profiles were assessed in 31 consecutive patients with glomerulonephritis and
      proteinuria > 0.3 g/24 h. All patients were treated with ACE inhibition for more
      than three months. Twenty patients consented to receive additional treatment with
      atorvastatin 10 mg daily in conjunction with a cholesterol-reducing diet, while
      11 patients received standard care. Analyses were performed at baseline and after
      six weeks. RESULTS: After six weeks of treatment with atorvastatin urinary
      protein excretion was reduced from 1.80 g/24 h to 1.42 g/24 h (22%, p = 0.005),
      while no change was observed in this parameter in the untreated patients over the
      same period. Plasma albumin did not change in treated or in untreated patients.
      Lipid and lipoprotein parameters improved in all treated patients (all p <
      0.001). No correlation was observed between the percentual changes in lipids and
      proteinuria. Plasma creatinine and creatinine clearance did not change (p >
      0.05). CONCLUSIONS: Six weeks of therapy with low-dose atorvastatin, added to ACE
      inhibition, resulted in a 22% decrease of proteinuria compared to untreated
      patients.

PMID- 15847251
TI  - Telmisartan in patients with mild/moderate hypertension and chronic kidney
      disease.
AB  - AIMS: This study assessed the clinical efficacy and safety of telmisartan, an
      angiotensin II receptor blocker with a long terminal elimination half-life and
      almost exclusively excreted in bile, in patients with varying severity of chronic
      kidney disease (CKD). PATIENTS AND METHODS: Adults with diastolic blood pressure
      (DBP) 90 - 109 mmHg and stable CKD were enrolled: mild/moderate (creatinine
      clearance (CrCl) 30 - 74 ml/ min/1.73 m2), severe (CrCl < 30 ml/min/1.73 m2) or
      requiring maintenance hemodialysis. A two- to four-week single-blind, placebo run
      in period preceded once-daily telmisartan 40 mg administration for four weeks.
      Telmisartan 80 mg was given after four- or eight-week treatment ifDBP > or = 85
      mmHg. After 12-week treatment, trough DBP/systolic blood pressure (SBP), DBP and
      SBP control rates, renal function and tolerability were recorded. RESULTS: Mean
      changes in DBP/SBP were 10.5/-10.7 mmHg for mild/moderate CKD (n = 27), -11.2/
      14.9 mmHg for severe CKD (n = 27) and -15.0/-21.1 mmHg for hemodialysis patients
      (n = 28). DBP control rates (< 90 mmHg)/SBP responses (< 140 mmHg or > 10 mmHg
      reduction) occurred in 59.3%/66.7%, 63.0%/70.4% and 71.4%/92.9% of mild/moderate
      CKD, severe CKD and hemodialysis patients, respectively. Incidences of drug
      related adverse events were low, and all were known adverse events of telmisartan
      and common to other angiotensin II receptor blockers. At the end of treatment, a
      decrease in 24-h urine creatinine occurred in 5/53 (9.4%) patients. Two patients
      discontinued treatment prematurely due to the worsening of CKD and one due to
      aggravated proteinuria. CONCLUSION: Once-daily telmisartan provided effective and
      well-tolerated treatment of mild/moderate hypertension in CKD patients, with no
      worsening of renal function.

PMID- 15847252
TI  - Characteristics of population with normal serum creatinine impaired renal
      function and: the validation of a MDRD formula in a healthy general population.
AB  - BACKGROUND AND AIMS: Glomerular filtration rate (GFR) provides the most accurate
      estimation of renal function. This study investigated the clinical
      characteristics of patients with impaired renal function having a normal serum
      creatinine level. We also validated whether the new Modification of Diet in Renal
      Disease (MDRD) formula can be applied in a healthy general population. MATERIAL
      AND METHODS: A total 393 participants who had serum creatinine concentration
      below 132.6 micromol/L without underlying diseases were randomly selected on an
      address basis in Ansan City. According to the level of GFR, they were divided
      into 3 groups and we analyzed their clinical characteristics. In 75 subjects, who
      were randomly selected 25 cases in each group based on GFR estimated by Cockcroft
      Gault (C-G) formula, true GFR was measured using the 99mTc-DTPA renal clearance
      method. RESULTS: A total 393 (male: 106, female: 287) participants were as
      follows: GFR < 60 ml/min/1.73 m2; 4% (n = 25); 60 < or = GFR < 90 ml/min/1.73 m2;
      26.2% (n = 103); GFR > or = 90 ml/min/1.73 m2; 67.4% (n = 265). In the group of
      decreased GFR, the mean age was older (67.4+/-10.7 vs. 48.7+/-12.8 vs. 39.4+/-8.2
      years, p < 0.001), the gender was male (90.33+/-28.77 vs. 110.55+/-31.64, p <
      0.001), and amount of proteinuria more increased (0.61 (0.56) vs. 0.33 (0.34) vs.
      0.38 (0.33) gm/day, p = 0.007). The accuracy and precision of each formula were
      assessed by the difference in GFR measured by the 99mTc-DTPA renal clearance
      method--estimated GFR by each formula (deltaGFR), and the coefficient of
      determination (r2) of different predictive equations. The results were as
      follows: deltaGFR = -14.78+/-46.03, r2 = 0.79 (24-hour urinary creatinine
      clearance), deltaGFR=-16.79+/-57.32, r2 = 0.66 (100/serum creatinine), deltaGFR =
      9.54+/-39.18, r2 = 0.87 (C-G formula), deltaGFR = -12.30+/-54.31, r2 = 0.66 (AASK
      formula), deltaGFR = 8.70+/-37.62, r2 = 0.79 (MDRD formula). Multiple linear
      regression analysis and logistic regression analysis showed that age, serum
      creatinine, total cholesterol and 24-hour urinary protein excretion were
      independently related to GFR and associated with a significant increase in the
      risk of decrement of GFR. CONCLUSIONS: From these results, a more accurate
      assessment of renal function should be required in a population characterized by
      older age, male gender and more proteinuria. The MDRD study formula and Cockcroft
      Gault formula have greater accuracy and precision with true GFR, and this
      equation can be applied in subjects with healthy general population.

PMID- 15847253
TI  - Benefit of continuous renal replacement therapy in subgroups of acutely ill
      patients: a retrospective analysis.
AB  - AIMS: Acute renal failure in the intensive care setting is common and impacts on
      patient's outcome. Continuous hemodialysis or hemofiltration offers theoretical
      benefit for patients with acute renal failure, but the clinical benefit has not
      been demonstrated in randomized trials. ICU patients with acute renal failure are
      a heterogeneous population and we hypothesize that patients with increased
      illness severity would benefit from continuous renal replacement therapy.
      METHODS: From a comprehensive ICU database, we identified patients with acute
      renal failure exposed to continuous or intermittent renal replacement therapy. We
      a priori identified a subgroup of patients with multiple organ dysfunction
      syndrome, then used survival analysis to assess the effect of dialysis modality
      in the overall acute renal failure population and in the subgroup with increased
      illness severity. RESULTS: We identified 66 patients treated with intermittent
      and 36 patients treated with continuous renal replacement therapy. Patients with
      severe illness were preferentially selected for treatment with continuous
      dialysis (p = 0.01). Overall, there was no significant difference in survival
      between patients treated with intermittent or continuous dialysis. The relative
      risk of in-hospital mortality was significantly decreased in patients with
      multiple organ dysfunction syndrome (relative risk = 0.42+/-0.22, p = 0.027)
      treated with continuous therapy as compared with intermittent therapy. Among the
      survivors, continuous dialysis did not appear to hasten the return of renal
      function. CONCLUSIONS: This retrospective study suggests that continuous dialysis
      may be beneficial in a subgroup of ICU patients with multiple organ dysfunction
      syndrome or severe sepsis. Further randomized trials of dialysis modality should,
      if possible, concentrate on this population.

PMID- 15847254
TI  - Hypotension during hemodialysis results from an impairment of arteriolar tone and
      left ventricular function.
AB  - AIMS: Hypotensive episodes are a major complication of hemodialysis. Hypotension
      during dialysis could be directly related to a reduction in blood volume or to a
      decrease in cardiovascular activation as a response to decreased cardiac filling.
      A decreased cardiovascular activation could be due to patient-related or to
      dialysis-related factors. In order to study the isolated effect of a reduction in
      filling pressure, lower body negative pressure (LBNP) causes activation of the
      cardiovascular reactivity with a decrease in cardiac filling, but without the
      influence of the dialysis procedure that could affect cardiovascular reactivity.
      METHODS: We studied the relationship between relative blood volume (RBV), central
      venous pressure (CVP), systolic arterial pressure, heart rate, stroke volume
      index (SI), and total peripheral resistance index (TPRI) during a combined
      dialysis/ultrafiltration and during LBNP to -40 mmHg in 21 hemodialysis patients
      with a high incidence of hypotension. Systolic arterial pressure, heart rate, SI
      and TPRI were measured by Finapres. CVP was measured after cannulation of the
      jugular vein. During dialysis RBV was measured by a blood volume monitor (BVM).
      In order to study the conditions in which hypotension occurred after dialysis, we
      divided the patients into 2 groups: hypotensive (H) and non-hypotensive (NH)
      during dialysis. RESULTS: Baseline levels did not show any significant
      differences. During dialysis systolic arterial pressure declined gradually in the
      H group from 30 minutes before the onset of hypotension. There was a similar
      decrease of RBV and increase of heart rate in both groups with a large
      interindividual variation. At hypotension, H patients showed a significantly
      smaller increase in TPRI as compared to NH patients. The reduction in SI tended
      to be greater at hypotension, while CVP decreased to a similar extent in both
      groups. Moreover, during LBNP, a similar reduction in CVP resulted in a much
      smaller decrease in SI. Systolic arterial pressure was only slightly lowered due
      to a much greater increase in TPRI. CONCLUSION: We conclude that dialysis-related
      hypotension in our patient group did not result from an inability to maintain
      blood volume or from decreased cardiac filling. Hypotension appeared to result
      from the inability to adequately increase arteriolar tone and a reduction in left
      ventricular function. Both vascular tone and left ventricular function appeared
      to be impaired by the dialysis procedure.

PMID- 15847255
TI  - New worldwide trends in presentation of renal osteodystrophy and its relationship
      to parathyroid hormone levels.
AB  - AIMS: Abnormal mineral metabolism in chronic renal disease is associated with
      bone disease and extraskeletal calcifications. High turnover, hyperparathyroid
      bone disease, the most common form of renal osteodystrophy, has been the target
      for aggressive therapy. More recently, an increasing occurrence of low turnover
      bone disease has been reported. The present study was undertaken to evaluate the
      current prevalence of different forms of bone disease in a large population on
      chronic hemodialysis and its relationship to parathyroid hormone (PTH) levels.
      METHODS: Ninety-six chronic hemodialysis patients underwent double tetracycline
      labeled bone biopsy. Serum PTH levels were obtained in 52 patients at the time of
      biopsy. Bone formation rate (BFR/BS) was plotted vs. PTH levels in all patients
      and in subgroups with PTH ranges between 0-150, 150-500 and 500 - 1,200 pg/ml.
      RESULTS: The histomorphometric data showed that 40% of all patients were affected
      by osteitis fibrosa cystica (OFC). In the remaining 60%, various forms of low
      turnover bone disease were observed. There was no correlation between PTH and
      BFR/BS in all patients (r = 0.28) and in subgroups whose PTH levels ranged
      between 150 - 500 and 500 - 1,200 pg/ml (r = 0.027, r = 0.21), respectively. A
      close correlation between PTH and BFR/BS (r = 0.84, p < 0.05) was found only in
      the subgroup with a PTH level ranging low-turnover bone disease. The predictive
      between 0 - 150 pg/ml. CONCLUSIONS: The histomorphometric findings present a wide
      spectrum of renal osteodystrophy with a shift towardsvalue of PTH is limited as
      high-turnover osteodystrophy may present with low PTH levels and that with low
      turnover may occur with high PTH levels. In the latter parathyroidectomy should
      be avoided. We share the view that bone biopsy remains the "gold standard"
      diagnostic tool for renal osteodystrophy.

PMID- 15847256
TI  - Predictive factors of low HCO3- levels in peritoneal dialysis patients.
AB  - BACKGROUND: Metabolic acidosis is a major metabolic abnormality in end-stage
      renal disease (ESRD) and alkali is provided with dialysis treatment to patients
      on chronic peritoneal dialysis (CPD) to keep their acid-base balance within
      normal serum HCO3- levels. METHODS AND RESULTS: We examined the levels of venous
      serum HCO3- in 163 patients on CPD and the predictive factors for HCO3- levels
      low enough to indicate metabolic acidosis. The mean value for HCO3- was 26+/-2.4
      mmol/l and for anion gap was 13.1+/-3.1 mEq/l. A serum bicarbonate concentration
      of less than 24 mmol/l, compatible with metabolic acidosis, was observed in 13.5%
      of the patients. In a multivariate analysis HCO3- levels were directly correlated
      with older age and use of CaCO3- as phosphate binders, and inversely associated
      with serum potassium, the use of sevelamer and low lactate dialysis solutions.
      Higher serum urea levels, the use of low lactate solutions and sevelamer instead
      of CaCO3 were significantly predictive factors for HCO3- levels < 24 mmol/l.
      CONCLUSIONS: Venous HCO3- and anion gap values were within the normal ranges in
      stable CPD patients. In 13.5% of them, however, chronic metabolic acidosis was
      observed based on venous HCO3- levels < 24 mmol/l. Dietary protein intake, the
      use of sevelamer and low (35 mmol/l) concentration of lactate in dialysis
      solutions are important predictive factors for chronic metabolic acidosis in
      these patients.

PMID- 15847257
TI  - Thrombotic thrombocytopenic purpura associated with rapidly progressive lupus
      nephritis: report of two cases.
AB  - There are a few reported cases in the literature of thrombotic thrombocytopenic
      purpura (TTP), associated with systemic lupus erythematosus (SLE). We describe
      two cases of TTP which have been presented during rapidly progressive lupus
      nephritis, with grand-mal seizures, thrombocytopenia and microangiopathic
      hemolytic anemia. Both cases were treated with hemodialysis, plasma exchange,
      corticosteroids, cyclophosphamide and intravenous gamma-globulin. In both cases
      the TTP was improved but not the renal function. Further experience is needed to
      determine whether intensive and prompt treatment with plasma exchange,
      corticosteroids and chemotherapy leads to a favorable outcome, in cases of TTP
      associated with SLE.

PMID- 15847258
TI  - Henoch-schonlein purpura associated with esophagus carcinoma and adenocarcinoma
      of the lung.
AB  - Henoch-Schonlein purpura (HSP) is known to exist in association with a variety of
      malignant diseases including squamous and small cell lung cancer and
      hematological malignancies. We report the first cases of HSP associated with
      carcinoma of the esophagus and adenocarcinoma of the lung, respectively. We
      compare the main features of our patients with 23 previously published cases. We
      recommend that patients with HSP, especially men over 40 years of age, should
      undergo screening for occult neoplasia.

PMID- 15847259
TI  - Cryptosporidium infection in renal transplant patients.
AB  - Cryptosporidium parvum, an intracellular protozoan parasite, is a significant
      cause of gastrointestinal disease worldwide. Transmission can occur from an
      infected person, animal or fecally contaminated environment. The clinical
      manifestations of cryptosporidiosis are dependent on the immunologic state of the
      host. Infection among immunocompetent hosts results in diarrhea that is typically
      self-limited. In immunocompromised hosts, however, the infection may be
      protracted and life-threatening with no reliable antimicrobial therapy. In
      transplant patients, a course of antimicrobial therapy along with concurrent
      reduction in immunosuppression optimize immunologic status and may potentially
      lead to resolution of the infection.

PMID- 15847260
TI  - Hepatic portal venous gas associated with nonocclusive mesenteric ischemia in a
      hemodialysis patient.
AB  - Hepatic portal venous gas (HPVG) has been rarely described in chronic
      hemodialysis patients. We report a case of HPVG in a 59-year-old female patient
      with hemodialysis-dependent chronic renal failure due to diabetes who presented
      with acute onset of abdominal pain. Abdominal CT demonstrated the presence of gas
      in the portal veins. However, on laparotomy, no evidence of bowel necrosis or
      perforation could be found. HPVG seemed to be caused by nonocclusive mesenteric
      ischemia (NOMI), an increasingly recognized complication in hemodialysis
      patients. The patient responded favorably to intravenous hyperalimentation and
      antibiotics.

PMID- 15847261
TI  - Serious cardiac and pulmonary calcification in a young peritoneal dialysis
      patient: potential role of continuous correction of acidosis.
AB  - We describe a 40-month-old male infant with renal failure, treated with
      peritoneal dialysis, who developed massive calcification of soft tissues
      including the heart and lungs with subsequent cardiopulmonary insufficiency. A
      diagnosis of Jeune syndrome was made. After starting peritoneal dialysis, the
      patient exhibited an intractable metabolic acidosis of unknown etiology
      necessitating treatment with intravenous or oral sodium bicarbonate. Myocardial
      calcification was first detected by 2-dimensional echocardiography performed 3
      months after starting dialysis. The patient was not suitable for renal
      transplantation because of his cardiac dysfunction and died of cardiac and
      respiratory failure at the age of 6 years. Although the patient exhibited a
      variety of risk factors for ectopic calcification including hyperphosphatemia,
      hyperparathyroidism, high calcium-phosphate product and treatment with vitamin D,
      the early and massive soft tissue calcification may have been accelerated by
      correction of the metabolic acidosis. Therefore, the use of sodium bicarbonate
      may be involved in the etiology of the myocardial calcification.

PMID- 15847262
TI  - Perineal-onset Fournier's gangrene in a patient undergoing hemodialysis-
      importance of perineal-onset manifestation.
AB  - We present a rare case of perineal-onset Fournier's gangrene in a patient
      undergoing hemodialysis. A 51-year-old Japanese man manifested an acute-onset
      perineal pain with perirectal abscess; subsequently, the pain extended to the
      abdomen, chest, and loin despite quick treatment. His consciousness deteriorated
      to delirium and he died of septic shock on the third day of admission. Computed
      tomography (CT) revealed soft-tissue air along the right rectal wall, moreover,
      the infection extended to the anterior wall of the bladder and the right
      peripsoas muscle. On the basis of the clinical course and CT findings, the
      patient was diagnosed as having the complications of Fournier's gangrene,
      however, no scrotal lesions were detected. Fournier's gangrene is considered to
      be easily diagnosed on the basis of skin lesions, such as scrotal erythema and
      swelling. However, in the early stage, the diagnosis of Fournier's gangrene is
      difficult in a patient with perineal pain before the detection of skin lesions.
      In conclusion, definitely the key to improving the prognosis of this fulminant
      infection is the prompt recognition of the pathological process. Therefore,
      Fournier's gangrene should always be considered when patients undergoing
      hemodialysis manifest perirectal disorders, even when no scrotal lesions are
      detected, because there is the possibility of intra-abdominal and intra
      retroperitoneal infections resulting in septic shock.

PMID- 15847263
TI  - Mycobacterium chelonae exit site infection in a patient on peritoneal dialysis.
AB  - Atypical mycobacterial infe tion of the Tenckhoff catheter exit site is rare.
      Eradication of the infection is often difficult without the removal of the
      Tenckhoff cath ter. We report here a case of Mycobacterium chelonae exit site
      infection in a peritoneal dialysis patient. He was treated with a combination
      regimen of prolonged antibiotics, local heat therapy, deroofing and shaving of
      the Tenckhoff catheter outer cuff. This resulted in the successful treatment of
      the infection without the need for removal of the Tenckhoff catheter. We
      recommend that this therapeutic approach could be considered in similar cases and
      that removal of Tenckhoff catheter is not mandatory.

PMID- 15847265
TI  - [Let me remain the same].

PMID- 15847264
TI  - Laparoscopic cholecystectomy and inguinal hernia repair in a patient on
      continuous ambulatory peritoneal dialysis.

PMID- 15847266
TI  - [Historical flashes on prostatic symptoms and urinary retention].
AB  - OBJECTIVES: To perform a chronological search about symptoms of bladder outlet
      obstruction of prostatic origin and some of its treatments. METHODS/RESULTS: Over
      the years we have been collecting data about the topic from books and journals;
      we present them in such a way that they can be consulted chronologically. From
      more than 100 references we have selected the 60 most relevant to our judgment.
      CONCLUSIONS: Many ideas about the syndrome and the way to solve it have arisen,
      which vary from one time to another. For most urologists, the main operative
      complication has always been bleeding, leading to the development of a great
      number of techniques to avoid it. Infection, the other great complication,
      prompted that initially surgical maneuvers were performed very fastly and with
      the small incisions. In addition, big drainages were necessary.

PMID- 15847267
TI  - [Relationship between LUTS (lower urinary tract symptoms) and quality of life].
AB  - OBJECTIVES: To evaluate the impact of the lower urinary tract symptoms (LUTS)
      included in the IPSS on the quality of life and to determine the relationship
      between quality of life or total IPSS score and treatment. METHODS: Retrospective
      review of the IPSS questionnaire in 125 male patients who had consulted for LUTS
      between January 2001 and December 2003. Results were included in an Access
      database. Statistical analyses were done with the SPSS 11.0 software. RESULTS:
      17% of the patients showed severe symptoms in accordance to the IPSS score. In
      the quality of life evaluation grouped into two categories, 88% referred good or
      indifferent quality of life. In the evaluation of the association between IPSS
      individual questions and quality of life there was a significant association for
      all questions. Patients reporting worse quality of life had a 6 times higher risk
      of receiving treatment. With a mean follow-up of two years, 91% of patients who
      were not on treatment continued without it. CONCLUSIONS: The most severe symptoms
      are, the worse the quality of life. The independent parameters that most
      influenced decision to start treatment were quality of life and total IPSS.
      Frequency, weak stream and hesitation may explain quality of life on each
      patient.

PMID- 15847268
TI  - [Adrenal carcinoma: 7 year disease free survival after complete primary tumor
      resection and repeated resection of local-regional and distant recurrences.
      Review after one case with poor initial life expectancy].
AB  - OBJECTIVES: We report the case of a female patient with adrenal carcinoma who had
      undergone surgery and presented with local-regional and distant recurrences,
      emphasizing the importance of the aggressive surgical treatment to achieve long
      term survival which is unexpected sometimes. Currently, it represents the gold
      standard and all cases should be reported to stimulate other groups to work in
      this line. METHODS/RESULTS: We report the case of a 29-year-old female patient
      who consulted for left flank pain, being diagnosed of an adrenal tumor by
      radiological tests; she underwent surgical excision of a left adrenal carcinoma
      (stage II). Later on she presented with local-regional recurrences (2 times) and
      distant metastases (liver) undergoing excision in three procedures. Currently,
      the patient is alive and free of disease 7 years after diagnosis. CONCLUSIONS:
      Adrenal cancer recurrences have been considered lethal in the short-term.
      Nevertheless, an aggressive surgical approach of local recurrences and metastasic
      disease may significantly prolong patient's survival and, sometimes, leave the
      patient disease free several years after the diagnosis of the primary tumor.

PMID- 15847269
TI  - [Surgical details and complications from retransplantation into the iliac fossa
      for third and fourth kidney transplants].
AB  - OBJECTIVES: To analyze the surgical aspects and complications from
      retransplantation into the iliac fossa for third and fourth kidney transplants.
      METHODS: Retrospective study of the 34 third and 5 fourth transplants performed
      in our department. We analyze patient's characteristics, surgical aspects and
      complications, and graft outcomes. RESULTS: Mean patient age was 41.6 years. 67%
      of the first and second transplants had been lost to vascular problems (19%) or
      chronic rejection (48%). Average time from last transplant in the retransplanted
      iliac fossa was 9 years (3 days-17 years). There were not significant differences
      between the groups of first and second transplant and third and fourth in cold
      ischemia time, number of mismatches, and number of days on hemodialysis after
      transplantation; there were significant differences in receptor age, number of
      transfusions, maximum and current antibodies and donor age, all of which were
      higher in third and fourth transplants. The graft was basically implanted in the
      right iliac fossa (71%) through a lumbar-iliac iterative incision; vascular
      anastomosis were equally made to the common and external iliac vessels; ureteral
      reimplant was performed following an extravesical technique; simultaneous
      transplant nephrectomy of the previous graft was performed in 33% of the cases.
      59% of the cases had immediate diuresis and 49% did not require dialysis within
      the first 7 postransplant days. Surgical complications were mainly vascular: 4
      cases of hemorrhage, 3 venous thrombosis and 2 arterial thrombosis. There were
      also 4 cases of lymphocele, 1 perirenal hematoma, and 1 enterocutaneous fistula
      with an abscess of the surgical bed. There were no urologic complications in the
      series. Globally, there was 1 death (2.5%) secondary to hemorrhage and another 6
      grafts (15%) were lost to complications, 5 vascular thrombosis and 1 after
      surgical bed abscess. 1, 3, 5, and ten-year actuarial graft survival were 65%,
      52%, 40% and 28% respectively. CONCLUSIONS: Retransplantation into the iliac
      fossa for third and fourth transplants is associated with a small increase in the
      number of surgical complications, mainly vascular complications.

PMID- 15847270
TI  - [Prevalence of overactive bladder in Spain: a population-based study].
AB  - OBJECTIVES: The aim of this study was to assess the prevalence of the urinary
      symptoms suggestive of overactive bladder (OAB) in Spain based on the
      International Continence Society (ICS) 2002 consensus criteria as urinary
      urgency, with or without urge incontinence, usually with frequency and nocturia.
      METHODS: 1,669 real telephone interviews were conducted to adults aged > or = 40
      years. The sample size estimation was made according to the prevalence for OAB
      described in the Milsom paper stratified by age and gender due to the high
      variability observed between ranges. Appearance and prevalence of main OAB
      symptoms, medical diagnostic and therapy due to these symptoms data were
      collected. RESULTS: the sample population was 1669 aged > or = 40 years, 50.6%
      women and 49.4% men. The overall prevalence of symptoms suggestive of OAB
      according to the OAB definition from ICS report 2002 was 21.5%, significantly
      higher in women (25.6%) than men (17.4%)(p<0.05). Adjusting these data to Spanish
      National Census of year 2000, the prevalence was 19.9%, being higher as well in
      women (23.6%) than men (115.4%). Urge urinary incontinence and stress urinary
      incontinence were superior in women (16.7% vs 10.4% and 33.1% vs 7.9%
      respectively)(p<0.01). Urinary frequency > 8 voids/day was referred by 9.8% of
      women and 7.9% of men interviewed. 62% of men and 52.4% of women reported they
      get up at night to void. A total of 52.1% of patients with urinary symptoms
      suggestive of overactive bladder reported they had consulted a doctor anytime
      before the interview due to urinary disorders and 16.7% was currently receiving
      treatment for some of these symptoms. CONCLUSIONS: Prevalence of urinary symptoms
      suggestive of Overactive Bladder is high in this study, in accordance with data
      from international studies. Urinary urgency, symptom which defines the pathology,
      is more prevalent in Spanish women than men. Further studies are needed to better
      assess OAB impact in the Spanish general population.

PMID- 15847271
TI  - [Diagnostic antegrade ureteroscopy of the upper urinary tract in the orthotopic
      neobladder].
AB  - OBJECTIVES: To demonstrate the usefulness of antegrade endoscopical examination
      in the evaluation of the upper urinary tract pathology in patients with
      orthotopic neobladder. METHODS/RESULTS: We present the technique of percutaneous
      antegrade ureteroscopy and the indications for treatment of the upper urinary
      tract urothelial tumor (radical or conservative) depending on multiple pyelo
      calyceal biopsies and tumor lesions. CONCLUSIONS: Endoscopical evaluation of the
      upper urinary tract in patients with orthotopic neobladder offers safer
      information than urine analysis, urine cytology, and the various radiological
      tests. The difficulty for retrograde examination is on the identification of the
      ureteral neomeatus, so that in case of failure, antegrade percutaneous approach
      allows complete ureteral and pyelocalyceal examination and biopsies thanks to the
      development of flexible endoscopes. The information supplied by these
      endoscopical examinations of upper urinary tract urothelial tumors (grade, stage,
      multifocality) allows the choice of radical or conservative (open surgery or
      endoscopical) treatment.

PMID- 15847272
TI  - [Percutaneous renal surgery with minimal access: miniperc].
AB  - OBJECTIVES: To describe the technique of the minimal access percutaneous
      nephrolithectomy, miniperc, and to analyze the results obtained with this
      treatment in adult patients. METHODS: We performed 42 minipercs between august
      2002 and December 2003. Mean patient age was 48 years (19-62). The procedure was
      undertaken using a 14Fr Amplatz sheath. Stone size varied from 1.5-3.5 cm in
      longest diameter (1.5-7 cm2). Lithofragmentation was performed by pneumatic
      lithotripsy. RESULTS: Average procedure time was 75.2 min. (range from 60 to
      120). All patients were discharged within 24 hours. Only three patients (7.1%)
      have a hematocrit descent over 2 points. No nephrostomy tube was left for the
      postoperative time. 95.2% of the patients were stone free 1 month after surgery.
      CONCLUSIONS: Our results make us consider the minimal access percutaneous
      nephrolithectomy (Miniperc) a minimal option for the elimination of renal stones,
      with low morbidity, diminishment of the hospital stays, very low analgesic
      demand, and no transfusion requirements.

PMID- 15847273
TI  - [Localization of prostate cancer within the central gland by endorectal MR
      spectroscopic imaging].
AB  - OBJECTIVES: The endorectal MR spectroscopic imaging is a new imaging test which
      allows more accurate and reliable localization and staging of prostate cancer
      than simple endorectal MRI. The combination of spectroscopic MR and MRI has
      recently achieved technical improvements that increased reliability in the
      detection of prostate cancer. Our group is now working in the detection of
      prostate cancer with the spectroscopic MR, in co-operation with the Agency for
      the Evaluation of Technology for Medical Research (Agencia de Evaluacion de
      Tecnologia para la Investigacion Medica-AATRM); although we are waiting for
      definitive results, we can advance that this technique may be used as a good
      alternative for localization of prostate cancer in patients with previous
      negative biopsies in whom the suspicion of prostate cancer persists. METHODS: We
      present a series of 5 patients under control for permanent elevation of PSA with
      previous negative biopsies. We were performing ultrasound guided sextant biopsies
      every 6 months, after blood test for PSA. Endorectal MRI and spectroscopic MRI
      were performed to try to localize the prostate cancer so diminishing the number
      of biopsies. RESULTS: All patients in the series had a low intensity lesion
      within the normal low intensity of the central gland, with an obvious
      spectroscopic metabolic abnormality suggesting the existence of prostate cancer,
      as it was then demonstrated by biopsy. CONCLUSIONS: The endorectal MR
      spectroscopic imaging is a non invasive method which offers the ability to detect
      prostate cancer within the central gland with a higher reliability in selected
      patients. The central gland is an area in which prostate cancer is less commonly
      localized, but it often shows the same signal intensity than hyperplastic tissue,
      so that it is difficult to be detected by purely morphological methods.
      Endorectal MR spectroscopic imaging allows evaluating the metabolic disturbances
      in the whole gland, increasing the reliability of detection of prostate cancer
      both in the central and peripherical glands.

PMID- 15847274
TI  - [Paratesticular rabdomyosarcoma: report of one case in an adult patient].
AB  - OBJECTIVES: To report one case of right paratesticular rabdomyosarcoma in a 21
      year-old young adult. METHODS: After treatment with right radical orchiectomy
      through an inguinal incision it was classified as clinical group I A following
      the IRS-III (localized disease completely excised) and received adjuvant
      treatment with Vincristine and actinomicin D. RESULTS/CONCLUSIONS: The patient is
      disease free 18 months after surgery. We emphasize the importance of adjuvant
      treatment in the posterior evolution of the tumoral disease.

PMID- 15847275
TI  - [Old schwannoma: a rare type of schwannoma].
AB  - OBJECTIVES: We report one case of retroperitoneal schwannoma with unfrequent
      histological characteristics evaluating its clinical significance and therapeutic
      options. METHODS: We report the case of a benign retroperitoneal schwannoma as an
      incidental MRI finding in a 70 year-old female patient with symptoms of
      lumbosciatic pain for 6 months. We perform a bibliographic review. RESULTS: After
      surgical excision the diagnosis was retroperitoneal old schwannoma. No additional
      treatment was given. There is no evidence of recurrence on follow-up. The
      histological changes apparent in the cases of old schwannoma have been
      interpreted as degenerative, indicating a long evolution, which has motivated its
      denomination as old. Some cases have been diagnosed as malignant. CONCLUSIONS:
      The old schwannoma is a rare variety of the benign common schwannoma.
      Microscopically its shows areas of hypocellular tissue and pleomorphic nuclei
      suggestive of malignancy. Therapeutic management is similar to other benign
      retroperitoneal processes, surgical excision and follow-up.

PMID- 15847276
TI  - [Fournier's gangrene secondary to urethral catheterization].
AB  - OBJECTIVES: We report one case of Fournier's gangrene secondary to urethral
      catheterization. METHODS: We describe the clinical case, in which the initial
      cause was identified, and perform a short bibliographic review. RESULTS: Although
      Fournier's gangrene was initially considered as idiopathic in etiology, currently
      it is possible to identify the entrance site of the infection. In the present
      case the insertion of a urethral catheter was the starting mechanism, associated
      with factors such as diabetes and alcoholism which favour its development. The
      patient was treated by surgical debridement and partial urethrectomy but finally
      died. CONCLUSIONS: We want to point out that urethral instrumentation should be
      done by expert hands due to the severity of possible complications. We should
      insist in the need of precocious treatment with wide spectrum antibiotics,
      radical debridement and complete urologic evaluation.

PMID- 15847277
TI  - [Report of two cases of bladder and prostate oat cell tumors].
AB  - OBJECTIVES: To report two cases of bladder and prostate oat cell tumors with bad
      outcome, in accordance to the bibliographic review. METHODS: The case in the
      bladder was associated with squamous differentiation and adenocarcinoma. Radical
      treatment followed by adjuvant chemotherapy did not stop the fatal outcome which
      ended 13 months later in acute septicemia having developed multiple metastases.
      The case in the prostate presented as oliguria-anuria and bilateral
      hydronephrosis which required the placement of a nephrostomy tube in an emergency
      basis. Once diagnosis was achieved the extemal urinary diversion was converted to
      intemal to improve patient's comfort. There was no response to systemic
      chemotherapy and the patient died 4 months after diagnosis. CONCLUSIONS: These
      cases add to the rare presence of this pathology in the bibliography. In our
      country, 15 cases have been confirmed in the bladder and 5 in the prostate;
      around the world, 150 and 59 respectively. Although there is a certain tendency
      to think that radical treatment and chemotherapy is the least bad of the options,
      some consequences of conservative attitudes offer similar results, mainly when
      preserving the bladder.

PMID- 15847278
TI  - [Renal cell carcinoma associated with contralateral metacronous renal
      oncocytoma].
AB  - OBJECTIVES: To report one case of renal cell carcinoma and contralateral
      metacronous oncocytoma, and to perform a bibliographic review on the topic.
      METHODS: 52-year-old male patient with history of right radical nephrectomy for
      renal cell carcinoma. On his ten-year follow-up multiple lesions appeared in the
      left kidney. Partial nephrectomy was performed. Pathological study showed three
      oncocytomas. CONCLUSIONS: The presence of metacronous lesions in the
      contralateral kidney of a patient with history of renal cell carcinoma is rare.
      The presence of the same histological type of tumor should always be suspected
      and the management should follow this suspicion. Contralateral metacronous
      oncocytoma is a rare pathology which has not been reported in the literature so
      far.

PMID- 15847279
TI  - [D. Luis Cifuentes Delatte].

PMID- 15847280
TI  - RN fraudulently practicing nurse midwifery suspended.

PMID- 15847281
TI  - RN's testimony admissible re nursing negligence-not medical malpractice. Case on
      point: Broehm v. Rochester, 690 N.W.2d 721-MN (2005).

PMID- 15847282
TI  - Termination for poor work does not ipso facto disqualify one for benefits. Case
      on point: Hoover v. Community Blood Center, 153 S.W.3d 9-MO (2005).

PMID- 15847283
TI  - CMS is on the case as physician spending, part B premiums rise.

PMID- 15847284
TI  - Big changes coming in Medicare payments, cost sharing methods.

PMID- 15847285
TI  - Judge: bridge to Medicare is a bridge too far.

PMID- 15847286
TI  - [Glial fibrillary acidic protein in astrocytes of the human neocortex].
AB  - Glial fibrillary acidic protein (GFAP) is a brain astrocyte-expressed protein
      that is recognized as one of the main immunohistochemical markers of these cells.
      The aim of the present study was to investigate the structure of GFAP-positive
      astrocytes of human neocortex. Main types of GFAP-immunoreactive astrocytes in
      the human neocortex were characterized using immunohistochemistry and confocal
      laser microscopy. These are astrocytes of the layer I forming the surface border
      glial membrane, translaminar astrocytes of the layer I with very long processes
      penetrating several cortical layers, astrocytes of middle layers of the neocortex
      with a general organization of protoplasmic-type astrocytes which are involved in
      formation of perivascular border membrane, and typical fibrous astrocytes of the
      white matter. The data obtained will contribute to unification of evaluation of
      histopathologic processes observed in various kinds of gliosis in the CNS.

PMID- 15847287
TI  - [Structural organization of pedunculopontine tegmental nucleus in the dog's
      midbrain].
AB  - The aim of this study was to determine the borders of pedunculopontine tegmental
      nucleus (PPN) in the dog's brain and to describe its individual substructures on
      the basis of the cytoarchitectonic study of this nucleus. Using the methods of
      Nissl, Kluver-Barrera and histochemical demonstration of NADPH-diaphorase, which
      is a selective marker of cholinergic neurones of tegmental area, the analysis of
      fiber organization, morphological types of neurons and density of their
      distribution in PPN was carried out. As a result, mapping this nucleus in dog's
      brain was performed and the borders of its parts including a compact and a
      diffuse one were described. It was not possible to distinguish mesencephalic
      extrapyramidal area from the general composition of PPN.

PMID- 15847288
TI  - [Paleoamygdala: cytoarchitectonics, organization and cytological characteristics
      of neurons].
AB  - This investigation was aimed at the comparative analysis of cytoarchitectonics,
      neuronal organization and cytological peculiarities of dorsomedial, posterior
      medial and posterior cortical nuclei of rat amygdala. The series of brain frontal
      sections stained with cresyl violet and impregnated with silver nitrate using
      Golgi method were studied. It was shown that within the territory of the nuclear
      complex studied, the organization of the centers of the nervous system gray
      matter evolved from the nuclear-type into the screen-type. This formation belongs
      to a sparcely-dendritic neuronal system and it contains the neuroendocrine cells.
      As a result, it is suggested that on the basis of its structural organization and
      developmental mechanisms, the nuclear complex studied comprises a unified area of
      amygdala, which was formed at the earliest stages of its evolution, therefore it
      should be named a "paleoamygdala".

PMID- 15847289
TI  - [Peculiarities of cytochrome oxidase activity in the visual cortex neurons of
      kittens reared under the conditions of flickering illumination].
AB  - The objective of this study was to analyze the influence of the light flickering
      with the frequency of 15 Hz, on the neuronal metabolic activity in kittens reared
      under the conditions of mesopic illumination. The method for demonstration of a
      respiratory enzyme cytochrome oxidase was used to study the visual cortex areas
      17 and 18 and the lateral geniculate nucleus. It was shown that in kittens that
      were subjected to this stimulation as opposed to intact animals and to kittens
      reared under the conditions of mesopic illumination, specific changes in pattern
      of cytochrome oxidase distribution in area 17 took place. This change was
      manifested by the appearance of alternating zones of increased and decreased
      enzyme activity in layers III and IV. Within the cortical area 18 and lateral
      geniculate nucleus, no changes in the pattern of cytochrome oxidase activity
      distribution were detected in experimental kittens. It is suggested that
      flickering illumination results in disequilibrium of Y- and X-visual pathway
      activity.

PMID- 15847290
TI  - [Neurotransmitter stage in the development of peripheral part of autonomic
      nervous system].
AB  - The dynamics of neurotransmitter stage in the development of autonomic nervous
      system (ANS) was studied in rats starting from the moment of initial appearance
      of neurotransmitters acetylcholine and adrenalin in ANS peripheral part main
      nervous plexuses. Cryostat sections of embryos on developmental days 13.5, 16.5
      and 18.5 and of neonatal rats aged 0.5 and 1.5 days were treated with glyoxilic
      acid, using Karnovsky-Roots method and impregnated with silver nitrate according
      to Bielschowsky-Gross method. Acetylcholinesterase in vagus and in spinal ganglia
      was found on day 13.5, while catecholamine in sympathetic trunc was detected in
      animals immediately after the birth. Periods of the beginning of neurotransmitter
      stage in ANS development in rat and man were compared and it was established that
      it was delayed in rat as in immature-born animal.

PMID- 15847291
TI  - [Lens histamine-containing structures of the rat's eye].
AB  - The objective of this study was to analyze the distribution, localization and
      morphological features of lens histamine-containing structures. Studies were
      performed using the lenses of 37 intact outbred male rats sacrificed at the same
      time of the day. The methods of light and luminescent microscopy and
      cytospectofluorometry were applied to obtain the quantitative characteristics and
      detailed morphological description of histamine-containing structures in the
      different parts of lens. It was shown that all the epithelial cells and cells
      fibers of the lens contain histamine. Depending upon the degree of condensation
      of nuclear chromatin and their histamine content, the nuclei of lens cells could
      be subdivided into two types: type A nuclei with high histamine content and high
      degree of chromatin condensation; type B nuclei with low histamine concentration
      and slight chromatin condensation.

PMID- 15847292
TI  - [Histogenesis and structural organization of the walls of rat venae cavae and
      pulmonary veins].
AB  - Using light and electron microscopic methods, the histogenesis and structural
      organization of the walls of rat venae cavae and pulmonary veins were studied in
      prenatal and postnatal periods of development. The special attention was paid to
      the appearance of the striated myocytes in the walls of these vessels during the
      process of ontogenesis. The time of initial divergent development of myoblastic
      differon was established, the stages of differentiation of striated myoblasts and
      the peculiarities of intercellular junctions were characterized, as well as the
      innervation and vascularization of the walls of venae cavae and pulmonary veins.

PMID- 15847293
TI  - [Some microcirculatory and metabolic changes of rat myocardium following coronary
      artery occlusion].
AB  - The experiments conducted on 50 albino male rats have shown that the increase of
      capillary metabolic surface area and capillary bed capacity detected 1-15 days
      after the coronary artery occlusion in the zones distant from necrotic focus, and
      resulting mainly from capillary dilation, correlated with the progressive
      reduction of lipid peroxidation intensity, decline in the necrotic focus area and
      in the activity of necrotic marker enzymes in blood serum. These changes were
      accompanied by a gradual increase in the activity of some enzymes and substrate
      content that characterize the myocardial energy supply. The changes detected
      could be regarded as a result of improvement of microcirculatory blood supply to
      the myocardium. while a prolonged (lasting for 15 days) increase of myocardial
      lipid peroxide content could reflect the natural reoxygenation arising from a
      collateral circulation development.

PMID- 15847294
TI  - [Loss of the myofibrils as the manifestation of relative dedifferentiation of
      hypertrophied cardiomyocytes].
AB  - The material of intraoperational biopsies of right ventricle obtained from 54
      patients aged 9-40 years with Fallot's tetrad was studied to analyze the changes
      of cardiomyocyte (CMC) ultrastructure and dimensions in the process of their
      hypertrophy. The results of the present investigation and the analysis of the
      literature indicate, that CMC ultrastructural remodeling in course of their
      hypertrophy follows the pattern of progressive dedefferentiation. Therefore, the
      loss of the myofibrils at the advanced stages of hypertrophy is not the
      manifestation of CMC degeneration, but is the result of their relative
      dedifferentiation. Relative dedifferentiation combines the processes of
      remodeling of hypertrophied CMC and CMC in a state of chronic hibernation. CMC
      dedifferentiation in the course of these processes may have a common nature and
      may reflect the variants of a single general biological phenomenon.

PMID- 15847295
TI  - [Structural-functional organization of dark and light smooth myocytes in the
      musculature of visceral organs].
AB  - Using electron microscopy, the smooth musculature of human and laboratory animal
      bronchi, intestine and ureters was found to contain smooth myocytes of light and
      dark types, which had the cytoplasm of different electron density. Both types of
      myocytes are characterized by a high degree of differentiation. The significant
      differences between light and dark myocytes were detected in the ultrastructural
      organization of their contractile elements. On the basis of data obtained, light
      and dark myocytes should be considered as mature cells in different phases of
      their functional activity. Some part of them, light myocytes, are in the state of
      "passive" contraction and may serve as a tissue functional reserve. Mutual
      transformation of light and dark myocytes seems to be possible and may be caused
      by functional requirements, which are realized at the level of tissue regulation.

PMID- 15847296
TI  - [Changes of structure and function of spleen macrophages induced by malignant
      neoplasia].
AB  - Spleen macrophages, as most active elements of the mononuclear phagocyte system,
      were studied using light and electron microscopy in experimental rats and mice
      with differenet types of malignant neoplasia, including chemically induced
      carcinogenesis, transplantable tumor growth and in leukosis. In chemically
      induced carcinogenesis macrophage phagocytic activity was reduced,
      morphologically, the cellular surface smoothing, cytoplasm organell reduction and
      nuclear pyknotic changes were found. In animals with transplanted tumors, high
      activity of spleen macrophages was detected. In animals with leukosis,
      macrophages are characterized by reduced phagocytic activity, smoothed cellular
      surface and a variable number of lysosomes. The results obtained support the
      concept of high reactivity of the cells of mononuclear phagocyte system in
      neoplasia.

PMID- 15847297
TI  - [Erythrocyte ultrastructure in norm and pathology: morphological phenomena and
      clinical correlations].
AB  - Using transmission electron microscopy, erythrocyte ultrastructure in norm and
      pathology was described. Among the morphological phenomena, most common were
      local and extensive erythrocyte plasmalemmal defects in the form of its
      loosening, thinning, consolidation and thickening, rupture, fragmentation,
      exfoliation from stroma with the formation of cavities. Plasmalemmal destruction
      may be accompanied with the formation of micro- and macroexovesicles, some of
      which lose the connection with the erythrocyte. Morphological signs of
      erythrocyte stromal disorganization included irregular distribution of hemoglobin
      granules with the formation of the regions of increased and decreased electron
      density, loosening of the internal structure up to the formation of cavities, as
      well as endovesicles, partially containing small or large osmiophilic particles.
      It was shown that in pathological processes of different genesis (malignant
      tumors, chronic bronchitis, burn trauma, schizophrenia) ultrastructural changes
      of erythrocytes have typical character.

PMID- 15847298
TI  - [Histotopography and density of distribution of the endocrine cells in mucosal
      epithelium of the large intestine of human fetus].
AB  - Histotopography and density of distribution (DD) of the endocrine cells in the
      mucosal epithelium of the large intestine of human fetus was studied using light
      microscopy. Endocrinocyte DD in the mucosal epithelium of the large intestine was
      found to increase progressively after their first appearance on the 9th week till
      the 12th week (average DD (164 cells per 1m m2 of mucosal section area-
      cells/mm2). Subsequently, in the 4th month, the tendency to a reduction of
      endocrinocyte DD (to 123 cells/mm2) was observed. In the 5th month, a sharp
      increase of this parameter was detected (reaching 205 cells/mm2), which
      represented the maximal value during all the periods of intrauterine development
      studied. In the 6th month cell DD decreased (164 cells/mm2). Dynamics of the
      changes of EC-cells, with the exception of those ones in the appendix and the
      rectum, was similar to that observed in the general population of endocrinocytes.
      In the rectum, EC-cell DD was stable during the 3rd, the 4th and the 5th months,
      while in the 6th months the tendency to its reduction was observed. In the
      appendix, the increase of EC-cell DD took place during all periods investigated.
      The maximal endocrinocyte DD in the epithelium of appendix in prenatal period of
      ontogenesis points to an essential role of endocrine apparatus function
      particularly in the intrauterine development.

PMID- 15847299
TI  - [Morphogenetic aspect of the influence of purified birch tar on skin].
AB  - Changes of the histological structure of rat's skin were studied two weeks
      following the daily applications of native birch tar and of purified birch tar,
      devoid of the components that could be potentially dangerous for humans. The
      morphometric investigations were performed with the use of computer technologies
      on the apparatus-programme complex (DiaMorph, Russia). It has been established
      that the main morphological manifestations of specific dermatotropic activity of
      birch tar in the present experiment included: epidermal hypertrophy,
      hyperkeratosis, stimulation of the activity of all dermal cellular elements,
      intensification of blood supply, reduction of sebaceous glands. Analysis of
      morphological findings indicates the bioequivalence of the native and purified
      birch tar in terms of its specific dermatotropic activity.

PMID- 15847300
TI  - [Interrelation of matrix vesicles with spatial distribution of mineral component
      in fibrous and hyaline cartilages].
AB  - Mineral components of the human fibrous and hyaline cartilages were studied by
      the methods of light, scanning, transmission electron microscopy and
      cryofractography. The interterritorial matrix of the fibrous cartilage was found
      to contain not only the local deposits of mineral in matrix vesicles, but also
      the calcified collagen fibrils and interfibrillar spaces forming the collagen
      fibers and occupying its major part. In the hyaline cartilage and in the
      territorial matrix of fibrous cartilage, mineral deposits were located in
      mineralized conglomerates, the basis of which was formed by matrix vesicles,
      surrounded by collagen fibrils and interfibrillar space substance. Such
      conglomerates participate in the formation of calcospherites.

PMID- 15847301
TI  - [Nitric oxide synthase and apoptosis activity in chondrocytes of articular
      cartilage in posttraumatic knee instability].
AB  - The dynamics of nitric oxide synthase (NOS) and apoptosis activity was studied in
      the in chondrocytes of articular cartilage of the patients with posttraumatic
      knee instability. Statistically significant increase of chondrocyte NOS activity
      was detected in the earliest period after the trauma (1.5 months). This was
      accompanied by the appearance of a great number of apoptotic cells in the zones
      of the cartilage with high NOS activity. Remarkably, these changes developed at
      the same time with statistically significant decrease of total matrix
      glycosaminoglycan content. These results suggest that there is a NOS-dependent
      signaling way of apoptosis that could participate in the development of early
      dystrophic changes in the cartilage.

PMID- 15847302
TI  - [NADPH-diaphorase topochemistry in human and rat knee joint structures and its
      changes in experimental arthritis].
AB  - Using the histochemical demonstration of NADPH-diaphorase (NADPH-d) activity, the
      distribution of constitutive nitric oxide synthase (NOS) activity was studied in
      the cartilage and synovium of healthy man and rats and in experimental arthritis.
      Arthritis was induced in rats by the injection of complete Freund's adjuvant; the
      material was studied at days 7, 14, 30 and 60 of inflammation. NADPH-d activity
      was different in man and rat. In human cartilage NADPH-d-positive chondrocytes
      were absent, whereas in synovium synovial lining cells and endothelial cells of
      microvessels were marked. In rats of control group and in those treated with
      adjuvant, high activity of the enzyme was demonstrated in the cytoplasm of
      proliferating chondroblasts situated in the marginal zone of the cartilage, and
      in chondrocytes, that formed the isogenous groups in its deep portions. In rat
      synovium, besides synovial lining and endothelial cells, fibroblasts were also
      stained. At experimental days 7 and 14 the number of the marked cells with
      predominantly high enzyme activity increased on the average by approximately
      30.4%. This parameter decreased significantly, approaching the control level at
      day 30, while at day 60 of adjuvant arthritis NADPH-d positive cells were not
      detected. Heterotopic localization of constitutive NOS indicates that NO is
      unequally involved in arthritis development in man and rat. The dynamics of
      enzyme activity depends on the stage of inflammation and determines the specific
      effect of NO on target cells.

PMID- 15847303
TI  - [Structural organization of human yolk sac epithelium during first three months
      of intrauterine development].
AB  - Epithelium of the endodermal origin in the human yolk sac was studied at prenatal
      weeks 5-12. In the beginning of the period studied the epithelium was
      characterized by high volume density, distribution in the different zones of the
      organ and polymorphism. The highest secretory activity of epitheliocytes was
      observed at weeks 7-8 of intrauterine development. After this period, epithelium
      total volume density decreased, while the fraction of inner epithelial lining
      layer increased. The epithelium-lined cavities in the yolk sac wall shrinked and
      disappeared, and the volumes of the cells and nuclei decreased. These
      morphological changes of the epithelium are indicative of the loss of the organ
      basic functions already by the end of embryonic period of human development.

PMID- 15847304
TI  - [Rating system of knowlege and skills control as a factor of direction of
      students' self-dependent studies in the Department of Histology of Medical
      University].

PMID- 15847305
TI  - [Mikhail Andreyevich Sreseli (to centenary of birthday)].

PMID- 15847306
TI  - [Pyotr Yakolevich Gerke (to centenary of birthday)].

PMID- 15847307
TI  - [On the work of Coordinating Council of International Association of
      Morphologists (Moscow, February, 2004)].

PMID- 15847308
TI  - [Scientific conference "Fundamental and applied problems of histology.
      Histogenesis and tissue regeneration" (St. Petersburg, April, 2004)].

PMID- 15847309
TI  - [Third Babukhin's reading in Oryol (Oryol, June, 2004)].

PMID- 15847310
TI  - [6th International Scientific Symposium "Application of Modern Analytical Methods
      to the Study of Cell Structure and Function" (Arkhangelsk, June, 2004)].

PMID- 15847311
TI  - Use of silicone oil in the management of complex retinal detachment--an Indian
      experience.
AB  - BACKGROUND AND OBJECTIVE: In the management of complicated retinal detachments
      (RD), temporary silicone oil tamponade has been increasingly used. This study
      reports results and complications of temporary silicone oil tamponade that was
      used to treat complicated RD associated with multiple etiologies. MATERIALS AND
      METHODS: Between 1988 and 1998, a total of four thousand four hundred and eighty
      eight (4488) eyes underwent vitreous surgery and silicone oil tamponade. Outcome
      measures were: anatomic and functional success and postoperative complications
      such as cataract, corneal changes, hypotony, and glaucoma. An eye was considered
      an anatomic success if there was a complete retinal reattachment or macular
      attachment. Functional success was defined as attainment of visual acuity of
      5/200 or better. Multiple logistic regression analysis was performed to elucidate
      the relationship between various pre- and postoperative variables and outcome
      measures. Mean follow-up was 17 months, and median, 8 months. RESULTS: Overall,
      anatomic success was achieved in 73% of the eyes, and functional success, in 47%.
      After removal of silicone oil, recurrence of retinal detachment was observed in
      9% of the eyes; a high percentage (70%) of eyes attained functional success.
      Postoperative cataract was observed in 65.3%, abnormal corneas in 21.3%, hypotony
      in 16.9%, and glaucoma in 16.4% of the eyes. CONCLUSIONS: Despite the onset of
      complications related to silicone oil usage, a high rate of reattachment of the
      retina was observed following vitrectomy and silicone oil tamponade in the
      management of complex RD associated with multiple etiologies.

PMID- 15847312
TI  - Vitreoretinal surgery for optic pit associated serous macular detachment: a
      discussion of two cases.
AB  - PURPOSE: To report the successful surgical outcome of two patients with a serous
      macular detachment and cystoid macular edema associated with a congenital optic
      nerve pit. METHOD: Case reports. Two patients with a serous macular detachment
      associated with a congenital optic nerve pit were treated with 360 degrees
      peripapillary endophotocoagulation during vitrectomy, attempted internal
      subretinal fluid drainage, and fluid-gas exchange. RESULTS: In both cases, the
      retina remained attached during a follow-up period of 6 months, and the patient's
      vision improved dramatically. One patient improved from the counting finger level
      to 20/70, and the other improved from 20/200 to 20/70. CONCLUSION: The use of 360
      degrees peripapillary endophotocoagulation after pars plana vitrectomy for the
      treatment of optic nerve pit associated retinal detachment resulted in excellent
      visual acuity and anatomic reattachment. Attempted internal subretinal fluid
      drainage was unsuccessful and did not contribute to the success of the case.

PMID- 15847313
TI  - Efficacy and safety of 1% rimexolone versus 1% prednisolone acetate in the
      treatment of anterior uveitis--a randomized triple masked study.
AB  - PURPOSE: To evaluate the efficacy and safety of 1% rimexolone versus 1%
      prednisolone acetate ophthalmic suspension in the treatment of anterior uveitis.
      METHODS: A randomised triple masked, parallel comparison of rimexolone and
      prednisolone acetate ophthalmic suspensions was carried out on 78 patients with
      acute, chronic and recurrent anterior uveitis. Treatment regimen included
      instillation of one or two drops of drug one hourly through the waking hours
      during the first week, two hourly in the second week, four times a day in the
      third week, two times a day for the first 4 days and once a day for the 3 days in
      the last week. The patient was clinically evaluated on the 3-4th, 7-10th, 14th,
      21st and 28th days. The patient was also reviewed on the 30th day. Anterior
      chamber cells and flare reactions were compared for evaluating the efficacy of
      the drugs. RESULT: Rimexolone is as effective as prednisolone acetate ophthalmic
      suspension in the treatment of anterior uveitis. The largest difference found was
      0.1 in the flare reaction (statistically insignificant; p = 0.3) and 0.2 score
      units (statistically significant; p = 0.01) in the cells. Overall, comparison of
      the drugs shows no clinical significance in the treatment of anterior uveitis by
      either drug. Difference in intraocular pressure (IOP) was also statistically
      insignificant (p > 0.05). However, three patients in the prednisolone acetate
      group and 1 patient from the rimexolone group showed a rise in IOP. CONCLUSION:
      Rimexolone 1% ophthalmic suspension is as effective as and safer than
      prednisolone acetate 1% ophthalmic suspension in the treatment of anterior
      uveitis.

PMID- 15847314
TI  - Causes of blindness and the results of cataract surgical intervention in the
      Micronesian islands: a retrospective study.
AB  - Since 1983, we have delivered eye care to inhabitants of the Micronesia islands a
      total of 18 times over an 18-year period. Approximately 14,000 islanders were
      examined. We diagnosed a total of 1226 blind eyes and 1231 eyes with low vision.
      Unoperated cataract (n = 765, 62.4%) was the leading cause of blindness in our
      data, and 611 cataract operations were performed. The preoperative visual acuity
      of the patients who underwent cataract surgery was less than 20/200. Visual
      acuity improved in 588 cases (96.2%) after the surgery. Sight-threatening
      complications occurred in 1.1% (7) of the eyes after the surgery, which is
      comparable to the rate in developed countries. Corneal opacity secondary to
      infection (11.2%) was the second leading cause of blindness in our data. Diabetic
      retinopathy (9.9%) was a cause of low vision in our data, and the number of eyes
      diagnosed with diabetic retinopathy in each district increased over the years.
      Glaucoma was the cause of blindness in 1.9% of the blind eyes, although the
      percentage may actually have been higher because visual loss was assessed only by
      reduced visual acuity. The demand for correcting refractive errors that caused a
      visual acuity of less than 20/60, was evident throughout the region. The majority
      of blind individuals in this study were suffering from operable cataract and good
      results were obtained with cataract surgery in this region. Further training of
      local medical staff would significantly improve eye care services in Micronesia.

PMID- 15847315
TI  - Age-related modifications of the corneal endothelium in adults.
AB  - PURPOSE: To obtain the topographical distribution of the corneal endothelial cell
      density, in different age ranges. METHODS: Three hundred eyes of 204 healthy
      subjects (110 males (M) and 94 females (F)) aged from 20 to 83 years were
      evaluated. Participants were divided into three groups according to age. First
      group (120 eyes) comprised patients aged from 20 to 44 years (mean 32.27 +/-
      7.5), the second group (110 eyes) comprised patients aged from 45 to 70 years
      (mean 54.13 +/- 7.1) and the third group (70 eyes), comprised participants older
      than 70 years (mean 79.28 +/- 5.9). Specular microscopy was performed in the
      central zone and in four peripheral points. RESULTS: Central and peripheral cell
      densities decrease with age (p < 0.05). In young adults the endothelial cell
      density did not show any significant variation in the central area with respect
      to the periphery (p > 0.05). In older adults the difference between central and
      peripheral endothelial cell densities showed the significance level of p = 0.05.
      CONCLUSIONS: Topographical distribution of the corneal endotheliul cell density
      is maintained lifelong. Age-related changes involve both center and periphery.
      The higher peripheral decrement observed in the ancient subjects could be
      considered as a major finding and in elderly a topographical disparity might
      occur.

PMID- 15847316
TI  - Serious eye and adnexal injuries from fireworks in Northern Ireland before and
      after lifting of the firework ban--an ophthalmology unit's experience.
AB  - BACKGROUND/AIMS: To report serious fireworks-related eye and adnexal injuries
      presenting to the Department of Ophthalmology in the Royal Victoria Hospital,
      Belfast. To assess the effect of lifting of the legislative ban on fireworks in
      Northern Ireland in 1996. METHOD: Twelve year retrospective review from 1990 to
      2001 inclusive of all ocular and adnexal injuries from fireworks requiring
      hospitalisation to the ophthalmology department. RESULTS: Twenty three patients
      with 23 injured eyes were reported. Six were female. The mean age was 18 years
      (+/- 13 SD). Six patients presented between the years 1990 and 1995. The
      remaining 17 patients presented between 1996 and 2001. Nearly half of the
      patients required ophthalmic surgical procedures. Thirty-six percent of patients
      had a final visual acuity of 6/60 or less. Superficial trauma not requiring
      hospitalisation was not included. CONCLUSION: Removal of the legislative ban on
      fireworks in 1996 has had a significant effect on the incidence of eye injuries.
      These injuries are potentially preventable with stricter control on the
      availability of fireworks and a greater awareness of the ocular risks they pose.

PMID- 15847317
TI  - A review of the use of olopatadine in allergic conjunctivitis.
AB  - Ocular allergies are very common and range in intensity from mild, self
      resolving, acute conditions to serious, chronic disease that can severely affect
      vision. The vast majority of sufferers experience relatively mild symptoms, which
      are often seasonal in nature. Treatments should be simple, comfortable and very
      safe. They should be able to respond to an ongoing attack but also provide long
      term relief from symptoms. Mast cell degranulation is central to all forms of
      ocular allergic disease and so treatment has concentrated on preventing this
      process or antagonizing the effects of the primary mediator, histamine.
      Olopatadine is a relatively new selective H1 antagonist that has mast cell
      stabilizing properties and has been shown to affect release of TNFalpha and
      various cytokines from conjunctival epithelial cells. This paper reviews the
      local ocular use of olopatadine and discusses the place of the drug in the
      treatment of allergic eye disease.

PMID- 15847318
TI  - The contribution to ophthalmic literature from different regions of the world.
AB  - PURPOSE: To compare the volume of ophthalmic literature from the developed and
      developing countries. METHODS: We performed a retrospective review of the five
      highest scoring impact factor journals in ophthalmology within the 3 year period
      1998-2000 inclusive. Europe, North America, Australia, New Zealand and Japan were
      categorised as developed countries, all others were categorised as developing
      market economies. Correspondence, news articles and book reviews were excluded
      from our study. RESULTS: The developing world contributed to only 5.47% of the
      literature compared to the 92.19% from the developed world. The majority of the
      contribution to ophthalmic literature from the developing countries originated
      from Israel, S. America, China, Saudi Arabia, India, Singapore and Korea. 2.33%
      of literature was the result of collaborative research from the two groups.
      CONCLUSION: The developing countries account for 90.8% of world blindness,
      compared to 9.2% from the developed countries, there is therefore, an inverse
      relationship between the burden of world blindness and the contribution to the
      highest impact factor ophthalmic journals with the developed countries only
      contributing to 5% of this research.

PMID- 15847319
TI  - Effectiveness of octreotide, an antiproliferative agent, on wound healing
      reaction after glaucoma surgery in an experimental rabbit model.

PMID- 15847320
TI  - [Personality disorders in postoperative period of coronary artery bypass graft
      surgery].
AB  - Personality disorders (PD) are recognized among key maladaptive factors in
      postoperative period of coronary artery bypass surgery (CABS). However studies on
      PD among CABS patients are predominantly under psychological approach and
      information on clinical features is very limited. A present investigation aimed
      at assessing clinical features and prognostic value of PD in late post operative
      period of CABS (from 1 to 3 years). Using psychiatric, cardiological and
      psychological methods, 48 patients (42 male, mean age 61.3 +/- 8.2 years) with
      diagnosis of PD and favorable cardiological status after CABS have been assessed.
      PD in post operative period is an important predictor of unfavorable social and
      occupational outcome of CABS. Three types of clinical course of PD were singled
      out: 1) hypohondric personality development; 2) "second life" personality
      development; 3) "denial of illness" reactions. Pronounced maladaptation was
      observed in type 1, most severe one--in type 2 and minimal maladaptation or its
      absence--in type 3. These types were differentiated by different repertoires of
      psychological defense mechanisms (PMD): type 1 was characterized by a limited
      number of them with a drift to mature mechanisms; PD of type 2 are featured by a
      narrow and rigid repertoire of defenses with predomination of immature mechanisms
      and in type 3 a maximum number of PMD with balanced involvement of mature and
      immature mechanisms was observed.

PMID- 15847321
TI  - [Neurological and mental disorders in combatants].
AB  - Four hundred and twenty patients admitted to the veteran's hospital with neuro-
      and psychopathology have been examined. Along with clinical, neurological,
      psychiatric and psychological methods, electroencephalography, computed
      tomography, electrocardiography, ultrasonic and X-ray methods for nervous system
      investigation as well as biochemical and immunological blood examination were
      used. The following disorders were singled out: (1) mental disorders--neurosis,
      personality pathology, post-traumatic stress disorder and different types of
      addictions (alcoholism, drug dependence): (2) consequences of craniocerebral and
      other injuries; (3) psychosomatic pathology. The prevalence, clinical
      manifestations and dynamics of each group of disorders are studied and their
      patho- and sanogenesis in terms of theory of functional systems are regarded.

PMID- 15847322
TI  - [Use of tremonorm in treatment of Parkinson's disease: outpatient experience of
      Moscow Municipal Health Care Service].
AB  - The efficacy of domestic drug tremonorm (levadopa-carbidopa) for Parkinson's
      disease (PD) treatment was studied. The treatment was conducted in neurological
      outpatient departments in several Moscow administrative regions and was
      administered to 142 PD patients, 15 being assigned to this drug for the first
      time and 127 being previously treated with other medications containing
      levadopa/carbidopa. A minimal effective dose (up to 500 mg) was selected for each
      patient and was not changed during 2 months. For patients previously switched to
      levadopa, the change for tremonorm has been done during 1 day if the dose of
      levadopa did not exceed 500 mg, and during 2 months in case a patient received
      over 500 mg per day. Modified Hoehn&Yahr scale, UPDRS, MMSE, PDQ-39 and other
      scales were used in complex evaluation of the disease stage. Positive effect of
      tremonorm was detected for 94 patients (66.2%), all of them continued tremonorm
      therapy after the end of the study. The most frequent side-effects proved to be
      dyspeptic symptoms. Tremonorm caused statistically significant positive changes
      in patient's movement scaled by UPDRS and the QL indexes in all PDQ-39 subscales.
      Positive changes in movement activity were accompanied by decrease of
      bradykinesia, tremor, better walking, writing and every day activity of PD
      patients. A change of nacom for tremonorm did not result in significant
      alteration of symptoms and Quality of Life indexes that suggest similar influence
      of these drugs on PD symptomatology. At the same time, a substantially lower
      price of tremonorm allows reducing of treatment costs.

PMID- 15847323
TI  - [Use of movalis in treatment of dorsopathy].
AB  - In regard to therapeutic effect of different medications used in dorsopathy
      treatment, non-steroid anti-inflammatory drugs rank first. Compounds selectively
      blocking COX-2 received special attention due to their minimal impact on COX-1
      that provides good anti-inflammatory and analgesic effect with simultaneous
      dramatic reduction of ulcerogenic activity. One of the first drugs with such an
      action is Movalis (meloxicam). Thirty patients were divided into 2 groups, the
      first including 22 patients with vertebral diseases and musculotonic syndromes;
      patients of the second group (8) had a pain syndrome caused by disk herniation.
      During the first 3 days Movalis was administered in the form of injections (15
      mg/day) and in the same doses in tablets for the following 20 days. After the
      treatment course, complete arrest of pain syndrome was observed in 33.3%
      patients, significant improvement--in 53.3% and insignificant effect--in 13.3%.
      Patients with reflex pain and musculotonic syndromes had a good analgesic effect
      after 3-day course of intramuscular injections, with the effect being mostly
      expressed in 8-10 days. Patients with diskogenic compressive radicular syndrome
      demonstrated a stable analgesic effect after a week of Movalis intake in tablet
      form. Movalis is well tolerated; side effects have occurred in 10 patients but
      they were minimal and did not lead to the change of medication dose or additional
      therapy.

PMID- 15847324
TI  - [Clinical efficacy of a novel hemorheological drug ascovertin in patients with
      vascular encephalopathy].
AB  - Patients with stages I and II of vascular encephalopathy developing on the
      background of atherosclerosis were treated with ascovertin during 21 days.
      Ascovertin is a complex of flavonoid dihydroquercetin and ascorbic acid. The
      study group included 21 patients aged 45-65 years and a comparison group
      consisted of 10 age-matched patients un treated with ascovertin. The ascovertin
      treatment relieved headache, reduced vertigo and fatigability, improved cognitive
      functions. The reliable diminishing of whole blood viscosity due to improvement
      of cellular rheology indices (decrease of aggregation and increase of erythrocyte
      deformability as well as decrease of indices of lipid peroxidation in erythrocyte
      membrane and blood plasma) was observed in the stydy group but not in the
      comparison one.

PMID- 15847325
TI  - [Cerebral hemodynamics and statokinetic functions in patients with vertebral
      basilar vascular insufficiency].
AB  - One hundred and forty-eight patients, aged 29-59 years, with vertebral basilar
      vascular insufficiency were studied before, during and after betaserc treatment
      in a dose 48 mg/day during 3 weeks. Along with neurological examination, cerebral
      dopplerography and computer stabilography methods were used. The main clinical
      appearances of cerebrovascular pathology of vertebrobasilar system were as
      follows: vertigo (93.2%), asthenia syndrome (91.2%), autonomic vascular disorders
      (63.5%) and stato-coordinative disturbances, the latter were represented
      primarily by disturbances of equilibrium system functions (83.8%). Cerebral
      dopplerography and computer stabilography were found to be reliable methods for
      patients with chronic insufficiency of cerebral blood circulation in vertebral
      basilar area. Drug betaserc (betahystine hydrochloride) effectively stops
      statokinetic disturbances in patients with discirculatory encelopathy in
      vertebral basilar area.

PMID- 15847326
TI  - [Correction of acute psychotic states in schizophrenia by rispolept solution per
      os].
AB  - To stop acute psychotic states during the first episode or relapses of
      schizophrenia, 37 patients were treated with rispolept solution per os during 2
      weeks. A procedure of a fast transition to optimal daily doses of the drug after
      1 day of treatment (searching period) with a following stabilization of mean
      daily doses (5.02-5.7 mg) at the stage of 14 day treatment course was used.
      Positive therapeutic effect by PANSS total score reduction, along with minor side
      effects, were found in 91.9% patients. Stopping effect of rispolept on acute
      psychotic states, emerging from day 1 of the treatment, and general antipsychotic
      and therapeutic action, beginning from day 2-3 and increasing to day 14, were
      stated out. Efficacy of the drug in syndromes differing by psychopathological
      structure is emphasized.

PMID- 15847327
TI  - [Topamax in treatment of resistant forms of epilepsy in adults and children].

PMID- 15847328
TI  - [Use of cavinton in neuropaediatrics].

PMID- 15847329
TI  - [Psychophysical development of children exposed antenatally to narcotic drugs].

PMID- 15847330
TI  - First ovarian maturity and recovery response in common carp, Cyprinus carpio
      after exposure to carbofuran.
AB  - The present study embodies the observations on duration (45, 75 and 105 days)
      dependent effects of toxicologically low concentration (16 ppm) of a carbamate
      pesticide, carbofuran, on first ovarian maturity with correlative recovery
      response by withdrawal of treatment for 30 days in virgin yearlings of common
      carp, Cyprinus carpio var. Communis. In control fish histological organization of
      ovary and changes in gonado-somatic index (GSI) revealed the initiation of oocyte
      differentiation and development at the commencement of experiment in December
      January and peak of maturation with fully grown yolky oocytes was attained by the
      time of termination of experiment in the end of March. In carbofuran exposed
      groups ovaries exhibited retardation of development and growth evident by
      significantly decreased GSI and predominace of immature oocytes passing through
      nuclear-cytoplasmic degeneration of variable magnitude. Severity of degenerative
      changes was more pronounced with prolonged duration. In recovery group ovaries
      had experienced regeneration as clued by the presence of oocytes of differential
      stages including vitellogenic and fully grown oocytes. In liver histopathological
      changes coupled with significant decrease in hepato-somatic index (HSI)
      attributed hepatic inactivation in all exposure groups whereas in recovery group
      an increase in HSI value with marked sign of hepatic reactivation was evidenced.
      No significant change in values of condition (CF) and somatic condition (SCF)
      factors substantiated the over all normal health of fish. Lipid and water content
      of ovary, liver and muscle registered the significant decrease at 105th day of
      exposure with concomitant augmented value for recovery group. These observations
      suggest that the commercial formulation of carbofuran, even at this
      toxicologically low concentration, is equally capable of affecting the first
      ovarian maturity with associated physiological implications but with
      reversibility in toxicity by withdrawal of pesticide exposure attributing
      regeneration in affected organs in due course time.

PMID- 15847331
TI  - Testicular cellular toxicity of cadmium : transmission electron microscopy
      examination.
AB  - It is clear that environmental heavy metals influence life systems and
      reproductive system. In the present study histological investigation revealed
      that cadmium was testicular toxicant in mice. Here we compared the fine-structure
      of spermatogenesis in two groups of mice (SWR), experimental and control. The
      experimental group underwent cadmium ingestion at 1 mg/kg daily for 4 weeks. The
      control group underwent ingestion of distilled water with equal dosages, using
      the same type of injectors, for 4-weeks. After cadmium exposure period both
      control and experimental groups were killed and samples of the testes were
      processed for microscopic examination. Ultra sections were examined and
      photographed by Transmission Electron Microscope (JEOL- 100SX) at 80KV.
      Ultrastructure examination revealed, vascular endothelial, interstitial, and
      sertoli cells damages. Early impairments of germinal cellular differentiation
      resulted in deformations in all parts of late spermatid. There were dislocation
      of accrosomal granules, nuclear damage associated with chromatin heterogeneity,
      detached spermatid from the apical process of sertoli cell, disarrangement of the
      mitochondria, abnormal oriented tail piece, and abnormal microtubules complex.
      These ultra morphological abnormalities relate to cell injury and to the
      resulting physiological abnormality, necrobiosis. Based on the results of this
      investigation it can be concluded that cadmium ingestion at 1000 microg/kg caused
      testicular toxicity and abnormalities in early sperm development.

PMID- 15847332
TI  - Reduced viability of F1 egg ropes in Chironomus riparius exposed to di-2
      ethylhexyl phthalate (DEHP).
AB  - The midge (Chironomus riparius), an aquatic invertebrate, was exposed to di-2
      ethylhexyl phthalate (DEHP) to evaluate the effects on reproductive processes via
      sediment toxicity. The test endpoints included emergence, sex ratio, fecundity
      and viability of F1 offspring egg ropes. After exposures of C. riparius to DEHP
      in this study, a significant result was observed only in the viability test of F1
      egg ropes. That is, hatching rates of F1 egg ropes from DEHP exposed adults were
      decreased significantly. This result provides the evidence that DEHP could lead
      abnormal egg ropes development by DEHP exposure during larval period. This means
      that DEHP could effect to Chironomus population density through reduced F1
      offspring.

PMID- 15847333
TI  - Level of heavy metals in some edible and poisonous macrofungi from Batman of
      South East Anatolia, Turkey.
AB  - The macrofungi specimens were collected and identified from locations around
      Batman province of Turkey. A group of 21 macrofungi were collected from 29
      different locations and analysed for the heavy metal contents. The highest Pb and
      Cu levels were found in Russula rubroalba while the highest Cd level was
      determined for the species Agaricus xanthodermus. Fe level was maximum for the
      species Funalia trogii; Mn for Mycena personsii; Zn level was for Morchella
      esculenta and Co level was for the species Agaricus xanthodermus. The lowest Cd,
      Cu, Mn and Zn contents were found in Inotus hispidus.

PMID- 15847334
TI  - Role of water hyacinth in the health of a tropical urban lake.
AB  - The paper assesses health of the tropical urban Robertson Lake, Jabalpur which
      receives domestic sewage from neighboring human inhabitation and is infested with
      water hyacinth. Peak density of this macrophyte was 12.5 t dw ha(-1). The water
      column was anaerobic (0.6 to 1.9 mg O2 L(-1)), neutral in pH, and enriched with
      inorganic carbon (23.5 to 37.1 mg L(-1)), NH4-N (0.48 to 2.96 mg L(-1)), and
      organic nitrogen and phosphorus. Density of heterotrophic bacteria was high (6.8
      to 15x10(5) cfu ml(-1)) along with that of total coliforms and fecal bacteria.
      Species diversity of phytoplankton and submerged macrophytes was very low.
      Growing stands of water hyacinth could store up to 613 g C m(-2), 23.5 g N m(-2)
      and 5.5 g P m(-2) and released them during decomposition. The release of
      nutrients was 3-4 times faster than the uptake. Water hyacinth stabilized water
      quality and provided substantial support to bacterial density, which in turn
      contributed significantly to its growth and nutrient dynamics. Turnover of water
      hyacinth was only 70-80%, adding approximately 175 t humus in the lake. The
      results denote poor health of the lake, characterized by low species diversity,
      fast shallowing, dominance of detritus food--webs, and the water unsuitable for
      human consumption.

PMID- 15847335
TI  - Assessment of deposition of MEMC (seed dressing fungicide) in exposed rice grain
      through study of seedling growth parameters.
AB  - Rice seed grains exposed to 240 ppm of seed dressing fungicide, MEMC showed
      increase in deposition of mercury with increase in period of observation (0h to
      48h) in 765+/-5 mg of intact endosperm. The gradual increase in mercury
      deposition in intact endosperm caused simultaneous decrease in mercury content of
      the seed coat. Exposure periods of 5 to 20 min with 240 ppm of MEMC showed 5.5 to
      8.72 microg of mercury deposition in 765+/-5 mg of intact endosperm. Increase in
      period of exposure (3 to 20 min) to 240 ppm of MEMC and also increase in chronic
      treatment to lower concentrations (1.5 ppm to 24 ppm) to seed grains have shown
      similar results in seedling growth parameters. Lower period of exposure or
      exposure to lower concentrations, both showed a significant inhibition of root
      growth, however the shoot growth showed stimulation. But higher exposure period
      or exposure to higher concentrations brought inhibition of both root and shoot
      growth. The exposure period showing 50% of root growth inhibition of 72h old
      seedling was calculated to be 10 min So also the chronic treatment showing the
      50% of root growth inhibition was calculated to be 9 ppm. Ten min exposure of
      rice grain to 240 ppm of MEMC showed deposition of 7.11 microg of mercury in
      765+/-5 mg of intact endosperm at 48h of observation (optimal phase of
      germinating process). Regression analysis indicated that by the time of 72h the
      intact endosperm and developing seedling might have acquired with a minimum
      amount of 10.23 microg of mercury from the seed coat. Finally it can be said that
      10.23 microg of MEMC might be bringing 50% root growth inhibition in 72h old
      seedlings and 16.71 microg of mercury causing 50% inhibition of both root and
      shoot growth of 120h old seedlings.

PMID- 15847336
TI  - Metabolic responses of tropical trees to ozone pollution.
AB  - Plants fumigated with 40ppbv, 80ppbv and 120ppbv concentrations of O3 exhibited
      significant reduction in total chlorophyll content, RuBP carboxylase activity and
      net photosynthesis. The reduction in total chlorophyll activity ranged from 12 to
      36% in Bauhinia variegata, 11 to 35% in Ficus infectoria and 3 to 26% in Pongamia
      pinnata on fumigation with O3, while the RuBP carboxylase activity was reduced by
      10 to 32% in Bauhinia variegata, 10 to 23% in Ficus infectoria and 9 to 15% in
      Pongamia pinnata. The net photosynthesis was also reduced by 6 to 26% in B.
      variegata, 16 to 39% in F. infectoria and 7 to 31% in P. pinnata on fumigation
      with 03. The relative higher sensitivity of tropical trees to O3 suggests that
      the ambient air quality standards in tropical tree areas need to be stringent to
      prevent vegetation from air pollution.

PMID- 15847337
TI  - Impact of air pollution on floral morphology of Cassia siamea Lamk.
AB  - Cassia siamea plants growing at two different sites (polluted and non-polluted)
      on two important roads of Agra city exhibited significant differences in their
      flowering phenology and floral morphology. The flowering in plants growing at
      polluted site is delayed and there was a marked reduction in flowering density,
      flowering period, size of floral parts, pollen fertility, fruit and seed-set. SEM
      observations revealed the presence of well developed glandular structures and
      reduction in the number and size of large stomata on the anther surface at
      polluted site. These changes were found to be closely associated with the extent
      of air pollution caused mainly by significant in the number of automobiles.

PMID- 15847338
TI  - Vegetation pattern related tc grazing pressure in alpine meadows of Nanda Devi
      Biosphere Reserve.
AB  - The present study aims to analyze the interaction of prevailing biotic pressure
      on plant species diversity in Nanda Devi Biosphere Reserve (NDBR) which lies in
      northern part of Uttaranchal hills between 79 degrees 40'E to 80 degrees 05'E
      longitude and 30 degrees 17' N to 30 degrees 41'N latitude and covers an area of
      2236.7 km2. A total of 75 species has been found which included the herbaceous
      plants viz., grasses, sedges and forbs. Generally, the plants have a short life
      span of 3-4 months. However, few species persist throughout the growth period
      i.e. May-October. Phytosociological study performed in plots of varying slope and
      grazing pressure intensity revealed that the dominant grasses were Danthonia
      cachemyriana and Poa annua and dominant forbs were Trachydium roylei and Geum
      elatum in all the plots. Grasses were abundant on west facing slopes while forbs
      preferred the even topography of east facing meadows. The grasses and sedges
      together had optimum density during July and August. In general, short lived
      species exhibited more diversity for one or two months whilst the long lived
      species exhibited optimum diversity althrough the snow free period. The species
      diversity is maximum (100%) in moderately grazed bughiyals i.e. Pacchu and
      minimum in intensively grazed bughiyals i.e. Martoli. The species distribution
      among the plots was 60-90% contagious and 11.2-38.0% randomirrespective of
      grazing pressure, thus highlighting the significance of grazing pressure in
      management of alpine meadows.

PMID- 15847339
TI  - Inhibitory effect of the plant Boerhavia diffusa l. against the dermatophytic
      fungus Microsporum fulvum.
AB  - Antifungal activity (reduction in colony diameter) of various extracts (pt.
      ether, chloroform, ethyl acetate, ethyl alcohol and aqueous) of aerial and root
      parts of Boerhavia diffusa (Nictaginaceae) was screened against dermatophytic
      fungi Microsporum fulvum. Statistically significant increase has been recorded in
      the % inhibition of the target fungal species with increasing test concentrations
      (1000-5000 ppm) of chloroform, ethyl acetate and ethyl alcohol extracts of the
      root. The maximum % inhibition observed in various solvent extracts of root was
      about 26% (chloroform), 46% (ethyl alcohol) and 57% (ethyl acetate) at 5000 ppm
      concentration with time exposure of 10 days. The colony diameter of the target
      mycelial colony decreased with increasing supplementation of the phytoextract,
      showing the presence of significant amount of some antifungal phytochemical
      moiety.

PMID- 15847340
TI  - Isolation and characterisation of antibiotic producing microorganisms in
      composted Nigerian soil.
AB  - Compost samples obtained from different locations within the premises of the
      university of Lagos were analysed to determine the presence and types of
      antibiotic-producing bacteria, fungi and actinomycetes using nutrient agar,
      potato Dextrose agar and starch casein nitrate agar respectively as culture
      media. A variety of bacteria were isolated and these included Staphylococcus
      aureus, B. subtilis, B. pumilis, B. lactesporus, B. megaterium, B. pulvifaciens,
      B. licheniformis, Streptococus spp., Corynebacterium spp. and E. coli. The fungal
      isolates encountered were Aspergillus niger, A. flarus, T. viridae, P.
      chrysogenum, P. pinofylum and Absida spp., while the following actinomycetes were
      identified: Norcadia spp., Micromonospora spp., Streptomyces scabies, S. reticuli
      and S. hygroscopicus. When these organisms were screened for antibiosis, the
      following species were found to be antibiotic producers: B. licheniformis, B.
      subtilis, Penicillium chrysogenum, Streptomyces reticuli, S. hygroscopicus and
      Micromonospora spp. The fungus Penicillium chrysogenum had the highest rate of
      antibiotic production with an inhibitory zone width of 17mm while Trichoderma
      viridae produced toxins lytic to other fungal hyphae.

PMID- 15847341
TI  - Root biomass and carbon storage in oriental spruce and beech stands in Artvin,
      Turkey.
AB  - In this study, influence of slope position (south-facing vs. north-facing),
      species type and sampling time on fine (0-2 mm), small (2-5 mm) and coarse (5-10
      mm) root biomass and carbon storage of oriental spruce (Picea orientalis) and
      oriental beech (Fagus orientalis) were investigated. Mean total root biomass of
      oriental spruce was 20160 kg ha(-1) in south-facing slopes and 17140 kg ha(-1) in
      north-facing slopes. Mean total belowground C storage of oriental spruce was 7861
      kg ha(-1) in south-facing slopes and 6840 kg ha(-1) in north-facing slopes.
      Similarly, biomass and C storage of oriental beech were 17190 and 6690 kg ha(-1)
      in south-facing slopes, and 13260 and 5200 kg ha(-1) in north-facing slopes,
      respectively. Oriental spruce had significantly higher fine root biomass than did
      oriental beech in south-facing slopes. Fine root biomass was significantly higher
      in fall than in spring in south-facing slopes.

PMID- 15847342
TI  - Effect of sulphur dioxide inhalation on serum Na and K+ ion concentration in
      albino rat.
AB  - A study was carried out to assess the effect of 60 ppm and 120 ppm exposure of
      sulphur dioxide gas for one hour daily for 2 and 4 week on serum sodium(Na+) and
      potassium (K+) ion concentration in albino rat, Rattus norvegicus (Berkenhout).
      The present findings reveal that serum sodium (Na+) ion concentration increased
      significantly after 4 week exposure to 120 ppm of sulphur dioxide, while serum
      potassium ion (K+) concentration decreased significantly after 4 week exposure to
      120 ppm of sulphur dioxide.

PMID- 15847343
TI  - Observations on life cycle of certain spiders from Western Ghats of Tamil Nadu.
AB  - Survey was conducted, in the different forests ecosystems of Western Ghats of
      Tamil Nadu in Nilgris, Coimbatore, Erode, Virudhunagar and Tirunelveli districts
      to collect the adult spiders and study them taxonomically. Fifty-six species of
      spider collections were made. From the fifty six, biology was studied for six
      spider species, such as Micrommata virescens n.sp., Oxyopes javanus, Peucetia
      virridana, Agelena kariansholensis n.sp., Heteropoda venatoria and Olios
      hampsoni. Biology studies with Peucetia virridana and Micrommata virescens showed
      that both species took more than 350 days to complete their life cycles.
      Heteropoda venetoria and Oxyopes javanus took more than 250 days to complete
      their life cycle. Agelena kariansholensis took 381 days and Olios hampsoni took
      345 days to complete their life cycles. 30% of Peucetia virridana and more than
      20% of Heteropoda venatoria and Micrommata virescens and 7% of Oxyopes javanus
      developed into adults in captivity.

PMID- 15847344
TI  - A preliminary report on effect of pulsed magnetic fields on fresh water fish
      (Labeo rohita) chromosomes.
AB  - Marine-life scientists around the world are already carrying out investigative
      trials to obtain higher yields under in-captive breeding conditions, on both
      edible varieties and ornamental fishes with optimal inputs. However, for such
      trials to succeed there is a need for genetic improvement. The idea that fish
      production can be enhanced by genetic manipulation is gaining acceptance, as
      there is a strong possibility that qualitative improvement of economically
      important traits can be achieved by identifying and utilizing more effective
      genotypes. In the present communication a tentative plan for genetic manipulation
      of fresh water fish using controlled, pulsed magnetic fields, is being discussed.
      Chromosome preparations of Labeo rohita were made using Colchicine-Methanol
      Acetic acid air drying technique, using tissue from gills. The fish were exposed
      to Pulsed Magnetic Field (PMF)with intensity 0.2 Gauss, pulsing at 50 Hz
      frequency (sine wave) for 6 hours / day for a total period of 30 days inside
      specially designed magnetic field enclosures. The karyological investigations
      revealed no distinct difference between "test" and "control" groups.

PMID- 15847345
TI  - Gill lesions in the major carp, Labeo rohita exposed to lethal and sublethal
      concentrations of tannery effluent.
AB  - The major carp, Labeo rohita were exposed to (0.873%) lethal and sublethal
      (0.073%) concentrations of tannery effluent for 24h and 40 days respectively
      under static bioassay condition. The surface architecture of gill revealed severe
      damages such as : fusion and clumping in the middle and distal parts of the
      primary lamellae, swelling and deterioration of the cells. The interlamellar
      space was filled either with hyperplastic epithelial or mucous cells. Secondary
      lamellae lost their identity and appeared finger like in structure in the lethal
      concentration and necrosis was observed in the primary and secondary epithelium.
      Swelling of primary and secondary epithelial cells was evident in sublethal
      concentration.

PMID- 15847346
TI  - A comparative study of Cu (II) biosorption on Ca-alginate and immobilized live
      and inactivated Cladosporium sp.
AB  - Spores of Cladosporium sp. were immobilized into Ca-alginate beads via
      entrapment. The alginate beads and both entrapped live and inactivated spores of
      Cladosporium sp. were used for comparison of biosorptive capacity from aqueous
      solutions. The factors affecting the adsorption ability on Cu (II), such as the
      contact time, initial pH, temperature were investigated. The results showed that
      the Ca-alginate beads containing live spores of Cladosporium sp. had the maximum
      biosorptive capacity. The biosorption equilibrium was established in about 3 h.
      The maximum biosorption of Cu (II) on Ca-alginate entrapping spores and no spores
      were obtained between pH 4.0 and 3.5. Temperature over the range of 15-45 degrees
      C had no significant effect on the biosorption capacity. The biosorptive capacity
      increased with initial concentrations in the concentration range of 30-800mg/l.
      The equilibrium was well described by Langmuir biosorption isotherms. The Ca
      alginate beads could be regenerated using 0.1M HCl, The biosorbents were reused
      in three biosorption-desorption cycles with negligible decrease in biosorptive
      capacity.

PMID- 15847347
TI  - Influence of sea salts on drainage water and soil chemistry of two different soil
      types: soil leaching experiments under laboratory conditions.
AB  - The effects of sea-salt on drainage water and soil chemistry was studied using
      two different soil types and setting up five soil-leaching experiments under
      controlled laboratory conditions. The objectives of the soil-leaching experiments
      were to provide information of the variability of soils and their drainage water
      chemistry following the input of different sea-salt solutions with different
      times which was similar to the precipitation input experienced during the storms
      in fields. Analyses were presented of major ions (Na+, Ca2+, Mg2+, Cl-, NO3-,
      SO4(2-) and NH4+) and pH for drainage water. At the end of the experiment, CEC
      (cation exchange capacity), %BS (percent base saturation), exchangeable capacity
      of Na, Ca and Mg and pH were also analysed for soil horizon chemistry. The
      results showed an increase in concentration of most of the major ions in the
      drainage water, though some adsorption of Na, Ca and Mg had taken place; so the
      result being a significant decrease in soil water pH. The chemical
      characteristics of each soil horizons also showed significant changes with the
      sea-salt applications compared to initial chemical characteristics. However,
      comparison of data from the four different sea-salt applications under different
      soil type or land-use didn't indicate the additional role that different land
      management could play in drainage water or soil chemistry.

PMID- 15847348
TI  - Response of tomato (Lycopersicon esculentum Mill.) to salinity in the early
      growth stages for agricultural cultivation in saline environments.
AB  - Salinity is a serious environmental problem. Growing of plants like tomato can be
      solution for coping with soil salinity. For this purpose, response of tomato to
      salinity has been tested in the early growth stages. Characteristics of
      germination (percentage and period; length and fresh-dry weight of radicle and
      hypcotyl) and seedling (length and fresh-dry weight of root, shoot and whole
      plant; leaf number and area based on Relative Growth Rate); Na+ and K+ content of
      leaf; K+/Na+ rate of leaf has been studied at the 0, 50, 100 and 150 mM NaCl
      levels. Thus, it determined that tomato can be indicator for agricultural
      cultivation at the salinity environments at the early growth stages.

PMID- 15847349
TI  - Influence of the organophosphorus insecticide phosphamidon on lentic water.
AB  - The inland freshwater resources are being increasingly subjected to heavy stress
      as a result of indiscriminate dumping of industrial wastes, domestic sewage and
      agricultural run-off causing deterioration of the water quality and adverse
      impact on aquatic biota. Pesticides drained to the aquatic environment are
      primarily of agricultural origin. Phosphamidon (widely used organophosphate
      pesticide in paddy field) significantly reduced dissolved oxygen (DO) at 1.8 mg/l
      exposure and reduced alkalinity at 0.9 and 1.8 mg/l. Hardness also reduced
      gradually but not significantly. Free carbondioxide was increased significantly
      at 1.8 mg/l of the insecticide compared to control. The insecticide had no
      influence on pH and temperature. There was maximum reduction of phytoplankton and
      zooplankton population at 1.8 mg/l of phosphamidon. Though gradual reduction of
      plankton community was also noticed at different lower concentrations of
      pesticides but in case of phytoplankton an abrupt reduction (about 50% of the
      control) was observed. The normal behaviour and feeding rate of air breathing
      teleost, Channa punctatus was also hampered. Therefore, phosphamidon even at low
      concentrations may create disorders in the aquatic ecosystem.

PMID- 15847350
TI  - Gonadosomatic and hepatosomatic indices of the freshwater fish Notopterus
      notopterus (Pallas) in response to some heavy metal exposure.
AB  - Area wise, the measurement of LC50 for pollutants is of great value in predicting
      the safe concentration dose of the contaminant in the environment on different
      aquatic species. The lethality of toxic substances including heavy metals to the
      aquatic organisms are usually assessed by following static bio-assay or
      continuous flow methods. The toxicity tests for mercuric chloride (HgCl2),
      cadmium chloride (CdCl2) and their mixture on Notopterus notopterus was
      determined by using 96h LC50 concentration on fish N. notopterus which indicated
      that cadmium chloride (CdCl2) was less toxic and mercuric chloride (HgCl2) was
      most highly toxic. The order of toxicity is mercuric chloride > mixture > cadmium
      chloride. On the basis of gonadosomatic index the reproductive cycle of N.
      notopterus can be categorised into immature, developing, maturing, mature, ripe
      and spent stages. Liver forms important organ of the body, which has a role in
      the ovarian development. On exposure to heavy metals at sublethal concentration
      both GSI (gonadosomatic index) and HSI (hepatosomatic index) are reduced.

PMID- 15847351
TI  - Euglenoid blooms in the floodplain wetlands of Barak Valley, Assam, North eastern
      India.
AB  - Red blooms of Euglena sp. in the floodplain wetland ecosystems of Barak Valley,
      Assam, India, were found to be induced by high concentrations of NH3-N, NO3, Fe,
      Mg and to some extent, PO4, Cu and Zn in their water. The trace elements were
      rapidly accumulated by the bloom organisms to high levels, whereby their
      concentrations in the water declined, leading to a collapse of the bloom, which
      tended to reappear as decomposition again led to the release of the nutrients.
      The bloom also harboured fairly high density of certain other algae and
      zooplankton, thereby acting as a sub-system within the wetland ecosystem. The
      bloom is non-toxic and is exploited as a fish food by the fish-farmers who
      artificially induce a bloom for augmenting the growth of surface-feeding species
      of fishes.

PMID- 15847352
TI  - Malarial hematopathy.

PMID- 15847353
TI  - Thrombocytopenia in malaria--correlation with type and severity of malaria.
AB  - AIM OF THE STUDY: Malaria is a major health problem in the tropics with increased
      morbidity and mortality. Thrombocytopenia is a common finding in malaria.
      Although a reliable diagnostic marker, prognostic implications could vary in the
      two types of malaria. This study was undertaken to correlate the presence and
      severity of thrombocytopenia with the type of malaria. DESIGN: A total of 1565
      subjects were included in the study and identified positive for malaria parasites
      on peripheral smear examination with conventional microscopy. Platelet count was
      done on a fully automated, quantitative, hematology Coulter analyser. RESULTS:
      Normal platelet count was noted in 21.6% cases. The mean platelet count in vivax
      malaria (n=973) was 1,15,390/microl (SD 64,580) with a range of 8000
      5,73,000/microl, as against falciparum malaria (n=590) where the mean platelet
      count was 100,900/microl (SD 75,437) with a range of 2000-497,000/microl (Pearson
      coefficient 8.825, p < 0.0001). Platelet count < 20,000/microl was noted in only
      1.5% cases in vivax malaria as against 8.5% cases of falciparum malaria, and none
      of the subjects with vivax malaria had a platelet count less than 5000/microl.
      CONCLUSION: Although absence of thrombocytopenia is uncommon in malaria, its
      presence is not a distinguishing feature between the two types. Thrombocytopenia
      less than 20,000/microl can occur in P. vivax malaria although statistically more
      common with P. falciparum malaria. The above findings can have therapeutic
      implications in context of avoiding unnecessary platelet infusions with the
      relatively more benign course in P. vivax malaria.

PMID- 15847354
TI  - Epidemic of leptospirosis: an ICU experience.
AB  - AIMS: To study the clinical profile and outcome of critically ill patients
      suffering from leptospirosis with organ dysfunction and correlate mortality with
      individual risk factors. METHODS: A study of critically ill patients suffering
      from leptospirosis was carried out in the Medical Intensive Care Unit of a
      tertiary centre of a metropolitan city between 1st June 2002 and 31st May 2003.
      All the patients in whom diagnosis was confirmed by ELISA IgM antibody testing
      underwent thorough clinical examination and necessary biochemical investigations.
      They received standard antimicrobial therapy and extensive supportive therapy as
      required. Mortality was correlated with individual risk factors. RESULTS: Out of
      834 total admissions in this period, 60 (7.2%) patients suffered from
      leptospirosis. There were 48 males and 12 females with age ranging from 12 to 60
      years, mean age being 40 years. The clinical manifestations varied from fever (58
      patients), jaundice (38), subconjunctival haemorrhages (24), to altered sensorium
      (22). All the patients had evidence of severe sepsis. Forty six patients had
      multiple organ dysfunction syndrome (MODS) and 26 required ventilatory support.
      The total mortality in leptospirosis patients was 52% which was much higher
      compared to the total MICU mortality (31.4%) in the same period. CONCLUSION:
      Leptospirosis is an important infection associated with high mortality when
      associated with organ dysfunction. The poor prognostic factors are preponderance
      of male sex, alcohol dependence, age group > 50 years, MODS, acute respiratory
      distress syndrome (ARDS), presence of acidosis and need for mechanical
      ventilation. However, timelyintervention and intensive therapy can save many
      young lives.

PMID- 15847355
TI  - Frequency of leptospirosis in patients of acute febrile illness in Uttar Pradesh.
AB  - OBJECTIVE: This study was performed to asses the disease burden of leptospirosis
      in and around Lucknow among patients presenting with acute febrile illness and
      conforming to the case definition of leptospirosis. METHODS: A total of 346 serum
      samples (mostly paired) and an equal number of urine samples were collected from
      patients presenting with acute febrile illness and fulfilling the criteria of
      clinical diagnosis of leptospirosis from January 2001 to December 2001. Patients
      attending a tertiary care hospital as well as from various communities in and
      around Lucknow were included in this study. All sera and urine samples were
      tested for the presence of IgM antibody by Leptodipstick test and by dark-field
      microscopy (DFM) respectively. All positive and 10% negative sera were tested at
      national leptospirosis reference centre at Andaman and Nicobar Islands for
      microagglutination test (MAT). RESULTS: IgM antibody was detected in 25/346 (7%)
      patients ranging in age from 9-65 years. DFM was positive in only in one case.
      MAT was positive in 4/17 cases tested and the prevalent serogroups were L.
      grippotyphosa and L. pomona in two each. Common presenting features in these
      patients were fever (25/25) and jaundice (17/25). History of contact with animal
      or water contaminated with animal urine was present in 96% cases. CONCLUSION:
      Leptospirosis is not uncommon in Uttar Pradesh. However larger epidemiological
      studies are required to know the actual disease burden. Dark-field microscopy is
      an insensitive method for the diagnosis of leptospirosis and is not suitable for
      surveillance.

PMID- 15847356
TI  - Comparative evaluation of the efficacy and tolerability of itopride hydrochloride
      and domperidone in patients with non-ulcer dyspepsia.
AB  - BACKGROUND: Prokinetic drugs are widely used for treatment of non-ulcer dyspepsia
      (NUD). AIMS AND OBJECTIVES: To assess the efficacy and tolerability of a new
      prokinetic agent, itopride hydrochloride in patients of NUD and compare it with
      domperidone. METHODS: Fifty-six patients who fulfilled the inclusion and
      exclusion criteria were enrolled in the study. Patients underwent upper
      gastrointestinal endoscopy to rule out organic pathology as a cause for their
      symptoms. The patient's symptoms were graded on a 4-point scale (0 to 3) at the
      beginning of treatment and at the end of Week-one and Week-two Patients were
      randomly allocated to receive either one tablet of itopride hydrochloride 50mg
      three times daily or one tablet of domperidone 10mg three times daily for two
      weeks. Pre-treatment and post-treatment hemogram, liver function and renal
      function tests, prolactin level and ECG were done in all patients. The response
      to therapy was evaluated by assessing the relief of symptoms at the end of two
      weeks on a 5-point scale. Statistical analysis was done using two-tailed paired t
      test; Wilcoxon matched pairs ranks sum test, Mann-Whitney-U test and chi-square
      test as applicable. RESULTS: Of the fifty-five patients enrolled in the study
      (age range of 18-60 yrs, median age of 35yrs), 26 were males and twenty nine were
      females. They had a median duration of symptoms for 4 weeks. Twenty-seven
      patients received itopride and 28 received domperidone. One patient did not
      follow up in the domperidone group, thus 54 patients were evaluable for analysis.
      Moderate to complete symptomatic relief was observed in 22 (81%) patients in the
      itopride group and 19 patients (70%) in the domperidone group (p > 0.05, NS).
      Both the drugs were well tolerated and neither caused prolongation of QT interval
      nor any abnormality in any serum biochemistry values. CONCLUSION: Therapy with
      itopride resulted in good symptomatic relief, was safe, well tolerated and
      comparable in efficacy to domperidone in relieving the symptoms of NUD. By virtue
      of its efficacy and tolerability, it could be an ideal choice for providing
      symptomatic relief to patients suffering from non-ulcer dyspepsia.

PMID- 15847357
TI  - Short stature. Congenital panhypopituitarism.

PMID- 15847358
TI  - Type VI Ehler Danlos Syndrome.

PMID- 15847359
TI  - NSAIDs and kidney.
AB  - NSAIDs are commonly used drugs. Even with the advent of selective COX-2
      inhibitors, nephrotoxicity still remains a concern. The adverse effects of NSAIDs
      are mediated via inhibition of prostaglandin synthesis from arachidonic acid by
      non-specific blocking of the enzyme cyclooxygenase leading to vasoconstriction
      and reversible mild renal impairment in volume contracted states. When unopposed,
      this may lead to acute tubular necrosis and acute renal failure. NSAIDs also
      produce interstitial nephritis with or without nephrotic syndrome secondary to
      minimal change disease. Although this presents as acute renal failure, it can
      progress in some cases to chronic renal failure. Papillary necrosis has been
      incriminated in the development of chronic renal failure secondary to NSAIDs. In
      patients on long term NSAIDs without acute or chronic renal failure, subclinical
      renal dysfunction such as reduced creatinine clearance and impaired urine
      concentrating ability has been shown to be present. Although this sub-clinical
      dysfunction is reversible on withdrawal of NSAIDs, some reports have suggested a
      persistent residual dysfunction. Even with a wide range of NSAIDs at our
      disposal, a renal safe NSAID is yet to be discovered.

PMID- 15847360
TI  - Vasculitis syndrome: an approach.
AB  - Vasculitides are clinical syndromes characterized by vessel wall inflammation and
      resultant organ damage. Pathogenesis involves autoimmune reactions from type I to
      type IV. Vasculitis may be primary or secondary to infective and connective
      tissue disorders. The extent of damage may involve multiple organ systems or may
      remain limited to skin only. As the vasculitic syndromes display a multitude of
      variable presentations, there can be no uniform laid out guidelines or evaluation
      scale for the diagnosis of these conditions. High degree of suspicion, a detailed
      history regarding onset of disease and course of illness, meticulous physical
      examination, and appropriate laboratory tests to determine organ systems involved
      and the extent of involvement, lead to the diagnosis of specific syndrome. Anti
      neutrophil cytoplasmic antibodies (ANCA), urinalysis, organ-specific biopsy and
      arteriography are the main diagnostic modalities for the diagnosis of vasculitis.

PMID- 15847361
TI  - Low birth weight and its implication in renal disease.
AB  - It has been demonstrated that intrauterine growth retardation, defined as birth
      weight below the 10th percentile, gives rise to a reduction in nephron number.
      Oligonephropathy has been suggested to increase the risk for systemic and
      glomerular hypertension in adult life as well as enhance risk for expression of
      renal disease after exposure to potentially injurious renal stimuli. Diseases,
      such as diabetes, that damage the kidney, may enhance this risk. In addition, it
      has been hypothesized that the same factors affecting kidneys in utero also
      impact on pancreatic tissue development, thus predisposing infants of low birth
      weight to an increased risk for the subsequent development of diabetes and
      diabetic nephropathy, consistent with the so-called "thrifty phenotype"
      hypothesis. Impact of low birth weight on nondiabetic renal disease has also been
      shown in some studies. In the current scenario, chronic kidney disease is
      increasing all over the world and the major two causes are diabetes and
      hypertension. Once the issues are shifting from management of end-stage renal
      disease to prevention of chronic kidney disease, prevention of low birth weight
      is likely to be an issue for the nephrologists in future.

PMID- 15847362
TI  - Dobutamine stress echocardiography--methodology, clinical applications and
      current perspectives.
AB  - Dobutamine stress echocardiography is often used as a non-invasive diagnostic
      modality for detection of coronary artery disease. In terms of accuracy it rivals
      SPECT scintigraphy. Application of non-coronary artery disease has made it an
      attractive diagnostic tool. However, like all diagnostic modalities it has its
      inherent limitations. Quantitation of stress echocardiography can resolve most of
      the problems surrounding its use.

PMID- 15847363
TI  - Pseudoaneurysm following lateral wall myocardial infarction.
AB  - Pseudoaneursym (PA) formation of left ventricle (LV) following acute myocardial
      infarction (AMI) is uncommon and is usually believed to be associated with a
      grave prognosis. We describe a case of 55 year old male patient presented with
      AMI and heart failure with a systolic murmur later diagnosed to have PA of the
      lateral wall of LV on echocardiography (transthoracic and transesophageal, TTE
      andTEE). Cardiac MRI and coronary angiogram (CAG) were performed. CAG showed 60%
      lesion at origin of major obtuse marginal artery (OM1). The patientwas advised
      surgical treatment, but he refused and took discharge against medical advice on
      27th dayof admission on stable condition.

PMID- 15847364
TI  - Right myocardial bridge on CT coronary angiography.
AB  - Myocardial bridging is a condition where the coronary artery traverses through
      the myocardium. Although it is not an uncommon finding in left anterior
      descending coronary artery (LAD), recently we came across a very rare case of
      right coronary artery (RCA) traversing through the right myocardium on CT
      coronary angiography.

PMID- 15847365
TI  - Neurocysticercosis presenting with psychosis.
AB  - Cysticercosis consists of infection with the small bladder-like larvae of the
      pork tapeworm Taenia solium. The life cycle of parasite is maintained between man
      and pig infected with cysticerci. Epilepsy is the most common presentation of
      neurocysticercosis; focal signs, headache, involuntary movements and global
      mental deterioration are other symptoms. Psychosis is a rare presentation and may
      be seen in up to 5% of patients. We present a 25 years old male, who had been
      under treatment from psychiatry OPD for psychosis for one year, developed
      generalized tonic-clonic seizures. CT scan of brain revealed multiple calcified
      and hypodense lesions with surrounding oedema. Histopathological examination of
      subcutaneous nodule confirmed the diagnosis of neurocysticercosis.

PMID- 15847366
TI  - Lactic acidosis in HIV-I infected patients receiving antiretroviral therapy.
AB  - Highly active antiretroviral therapy (HAART) has resulted in dramatic declines in
      morbidity and mortality in HIV-I infected patients in the developed world.
      However, with the availability of generic antiretroviral treatments (ART) in
      India, a large number of patients now receive ART. Increase in experience with
      ART has led to the detection of drug-related toxicities. We report herein
      potentially fatal side effects associated with the use of nucleoside analogues in
      HIV treatment--hyperlactatemia and lactic acidosis/hepatic steatosis.

PMID- 15847367
TI  - Oral Sildenafil in the management of primary pulmonary hypertension.
AB  - We report a case of primary pulmonary hypertension who benefited from oral
      Sildenafil therapy. Sildenafil, a selective phosphodiesterase type 5 inhibitor
      which acts as a pulmonary vasodilator, led to an improved clinical condition,
      exercise performance and haemodynamic parameters which were maintained at 6
      months of follow up. Larger trials are warranted.

PMID- 15847368
TI  - Myocarditis as an initial manifestation of systemic lupus erythematosus.
AB  - We report a case of systemic lupus erythematosus (SLE) whose initial presentation
      was in the form of myocarditis. The patient did not have arthritis, fever or
      butterfly rash. Presence of LE cell phenomenon, positive ANA, anti-DS DNA
      antibodies, leucopenia and high ESR with polyserositis indicated the diagnosis to
      be SLE. Therapy with steroid resulted in complete recovery. The patient developed
      atrial fibrillation during her course of acute illness which is being reported
      for the first time.

PMID- 15847369
TI  - Wilhelm Konrad Roentgen (1845-1923).

PMID- 15847370
TI  - Food-borne botulism.

PMID- 15847371
TI  - Diagnosis of leptospirosis utilizing modified Faine's criteria.

PMID- 15847372
TI  - Utility of intrapleural streptokinase in the management of chronic empyemas.

PMID- 15847373
TI  - Polyglandular autoimmune syndrome Type-I.

PMID- 15847374
TI  - From telepathology to virtual pathology institution: the new world of digital
      pathology.
AB  - Telepathology has left its childhood. Its technical development is mature, and
      its use for primary (frozen section) and secondary (expert consultation)
      diagnosis has been expanded to a great amount. This is in contrast to a virtual
      pathology laboratory, which is still under technical constraints. Similar to
      telepathology, which can also be used for e-learning and e-training in pathology,
      as exemplarily is demonstrated on Digital Lung Pathology
      (Klaus.Kayser@charite.de) at least two kinds of virtual pathology laboratories
      will be implemented in the near future: a) those with distributed pathologists
      and distributed (> or = 1) laboratories associated to individual biopsy
      stations/surgical theatres, and b) distributed pathologists (usually situated in
      one institution) and a centralized laboratory, which digitizes complete
      histological slides. Both scenarios are under intensive technical investigations.
      The features of virtual pathology comprise a virtual pathology institution (mode
      a) that accepts a complete case with the patient's history, clinical findings,
      and (pre-selected) images for first diagnosis. The diagnostic responsibility is
      that of a conventional institution. The Internet serves as platform for
      information transfer, and an open server such as the iPATH
      (http://telepath.patho.unibas.ch) for coordination and performance of the
      diagnostic procedure. The size and number of transferred images have to be
      limited, and usual different magnifications have to be used. The sender needs to
      possess experiences in image sampling techniques, which present with the most
      significant information. A group of pathologists is "on duty", or selects one
      member for a predefined duty period. The diagnostic statement of the
      pathologist(s) on duty is retransmitted to the sender with full responsibility.
      The first experiences of a virtual pathology institution group working with the
      iPATH server working with a small hospital of the Salomon islands are promising.
      A centralized virtual pathology institution (mode b) depends upon the
      digitalization of a complete slide, and the transfer of large sized images to
      different pathologists working in one institution. The technical performance of
      complete slide digitalization is still under development. Virtual pathology can
      be combined with e-learning and e-training, that will serve for a powerful daily
      work-integrated pathology system. At present, e-learning systems are "stand
      alone" solutions distributed on CD or via Internet. A characteristic example is
      the Digital Lung Pathology CD, which includes about 60 different rare and common
      lung diseases with some features of electronic communication. These features
      include access to scientific library systems (PubMed), distant measurement
      servers (EuroQuant), automated immunohisto-chemistry measurements, or electronic
      journals (Elec J Pathol Histol, www.pathology-online.org). It combines e-learning
      and e-training with some acoustic support. A new and complete database based upon
      this CD will combine e-learning and e-teaching with the actual workflow in a
      virtual pathology institution (mode a). The technological problems are solved and
      do not depend upon technical constraints such as slide scanning systems. At
      present, telepathology serves as promoter for a complete new landscape in
      diagnostic pathology, the so-called virtual pathology institution. Industrial and
      scientific efforts will probably allow an implementation of this technique within
      the next two years with exciting diagnostic and scientific perspectives.

PMID- 15847375
TI  - Thymus and thymoma: what's new?
AB  - The thymus is the prototype of lymphoid and epithelial organ that consists of
      lymphoid and epithelial cells. In spite of remarkable progresses made in the
      field of the immunohistochemical characterisation of the thymus parenchyma, the
      diagnosis of thymoma largely depends on the interpretation of conventional
      morphologic aspects. Histogenesis of this organ is a multi-step process, and many
      stages reproduce lesions and changes found in the adult thymus. The normal
      structure and its variants are extremely helpful to differentiate normal from
      pathologic aspects. Particular aspects of the thymus structures were shown in
      myasthenia gravis, despite the behaviour of thymoma in these patients is not
      clearly understood. Authors performed a detailed description of the conventional
      pathology of the thymoma, based on the new classifications, recently adopted. The
      immunohistochemical profile could be helpful in the diagnosis of many cases, and
      also seems to be useful in prediction of invasion that is the most important
      criterion in prognosis.

PMID- 15847376
TI  - Assessment of Gleason system use on different types of prostatic tissue samples.
AB  - One of the well-known and accepted methods of prostatic adenocarcinoma grading is
      Gleason system. The authors made a retrospective analysis of 221 prostatic
      adenocarcinomas divided into three groups (transvesical prostatectomies,
      transurethral resections and needle biopsies) following the type of surgical
      procedure used for drawing the tissue. Gleason scores and comparison between odd
      and even Gleason scores were assessed in the entire group and in each subgroup.
      High scores prevailed, meaning a tendency towards a low grade of differentiation.
      Even scores also prevailed meaning, on one hand, that, often, the examined
      specimen reveals only one pattern and, on the other hand, that surgical
      procedures as transurethral resections and unique needle biopsies cannot offer a
      sufficient material for examination, the multicentricity of prostatic carcinoma
      being well known.

PMID- 15847377
TI  - HOPE--a novel tool for the pathologist.
AB  - The growing demand for the detection of prognostic and diagnostic biomarkers by
      application of molecular-biological techniques has been slowed down to a large
      degree by the use of formalin and its influence onto antigenic structures and
      nucleic acids, although other reasons also exist. With regard to morphology a
      limitation in the possibilities, compared to frozen sections, takes place. With
      the introduction of the HOPE (Hepes glutamic acid buffer mediated Organic solvent
      Protection Effect) -fixation to date both have become possible; substantially
      enlarged possibilities concerning the detection of DNA, RNA and proteins in
      combination with excellent morphological results comparable to formalin-fixed
      tissues. We also highlight some aspects from our lung specific work during the
      last years. Immunohistochemical markers for differential diagnostics of
      malignancies in the lungs are discussed; their enhanced detectability using the
      HOPE-technique is pathbreaking for the future. The same holds true for the
      substantially enhanced detectability of germs (e.g. mycobacteria) in HOPE-fixed
      tissues.

PMID- 15847378
TI  - Hermaphroditism pathology.
AB  - Hermaphroditism is a more general term for the discrepancy between the phenotype
      and the genotype of sex development than sexual ambiguity, which refers mainly to
      external genitalia anomalies. Hermaphroditism is studied on an historical and
      pathogenetical perspective. Short embryological summaries are integrated. The
      defects of sexual differentiation due to a hormonal deficiency are first studied:
      androgen insensitivity, steroid 5 alpha-reductase 2 deficiency, defects of
      testosterone synthesis, persistent mullerian ducts syndrome. Sexual determinism
      deficiencies come after: Turner syndrome, XX males, pure gonadal dysgenesis, and
      true hermaphroditism, mixed gonadal dysgenesis, Drash and Frasier syndrome.
      Tumors of dysgenetic gonads followed. Mixed tumors developed in dysgenetic gonads
      are gonadoblastoma and dysgerminoma. Sex cord tumors are androgen insensitivity
      associated tumors, Leydig cells tumors and adrenal cell inclusion tumors. New
      perspectives open by sex reversion genes are open.

PMID- 15847379
TI  - The C-cells: current concepts on normal histology and hyperplasia.
AB  - We describe the current concepts on the embryology, normal morphology and
      immunohistochemistry of a minor cell population of the thyroid, the C-cells. We
      also try to make delineation between the normal number of the C-cells and C-cell
      hyperplasia. The two types of C-cell hyperplasia, physiologic and neoplastic are
      defined and characterized from morphologic and genetic point of view. Their
      relation with thyroid pathology, especially with medullary thyroid carcinoma is
      discussed.

PMID- 15847380
TI  - Cellular immune response in atypical tuberculosis diagnosed by PCR in paraffin
      embedded material.
AB  - The aim was to evaluate the cellular immune response in atypical tuberculosis and
      granulomatous inflammation consistent with tuberculosis (TBC), negative
      histochemically for acid-fast bacilli and analysed by PCR for Mycobacterium
      tuberculosis (MT) detection in paraffin-embedded tissue. Thirty six samples of
      differently localized atypical tuberculous lesions and granulomatous tuberculoid
      lesions negative for acid fast bacilli and 4 positive cases on Ziehl-Nielsen
      stain were analysed by PCR for MT detection and were tested immunohistochemically
      (IHC) for the cellular immune response in the granulomas and perigranulomatous
      tissue. The samples selected were: 7 pulmonary and 33 extrapulmonary specimens,
      especially lymph nodes. Histologically, the atypical tuberculous lesions
      contained supurative necrosis, defective granulomas and cellular polymorphism.
      The epithelioid cells showed frequent mitoses. The immunoprofile of cells was
      polymorphous. L26 positive small lymphocytes were found in nodular lymphoid
      aggregates surrounding granulomas. A significantly increased number of positive
      UCHL1 cells were found in 33 out of the 40 analysed cases, with a larger
      percentage of CD4 positive T cells (81.8% of cases). CD44 was positive in
      multinucleated giant cells (17.5% of cases), epithelioid cells (60% of cases) and
      lymphocytes (30% of cases). CD68 was localized in multinucleated giant cells and
      epithelioid cells, in a 4%, respectively 62.5% of cases. The PCR was performed in
      all 40 cases; the tissue samples were heterogeneous (lung, lymph nodes, lever,
      nasopharynx, etc.) and needed a good quality extraction of DNA. Performing a
      control PCR for Beta Globin tested the extraction; a good result was obtained in
      31 cases (77.5%); from these, 19 cases had amplification for IS 6110. The
      cellular immune response in the atypical tuberculous lesions was similar in cases
      with and without acid-fast bacilli, but positive for PCR. In the most cases with
      negative PCR reaction, it was due to a deficient fixation of the material. The T
      lymphocytes were numerous in all types of tuberculous granulomas, with the
      prominence of CD4 positive subtype. The immunoprofile of the epithelioid cells,
      positive for CD44 and CD68, presenting frequently mitoses suggests an activate
      state in a possible relationship to the T-cell-mediated immune response in
      tuberculosis.

PMID- 15847381
TI  - Variation of cephalometric parameters in peri-puberty cephalometric aspects of
      sexual dymorphism.
AB  - The data regarding the global and segmental growth and development of the child
      are useful in pluri-disciplinary studies which view the human body as an entity
      where the biological aspects (both the normal and the pathological ones)
      interlace with the socio-cultural ones, thus offering the possibility to any
      specialist in the field of humanities and morphological studies to cover a wide
      range in contemporary anthropological research. The development of the skull
      takes place in two active stages separated by a stage of relative quiet during
      the age of seven and puberty when the skull has a dolicocephalic aspect. During
      the second stage of active growth (which starts with puberty) there is a
      transversal growth of the basis of the cranium followed by an anteroposterior
      growth. The degree of gender-related differences as far as the dimensions and
      proportions of the skull are concerned vary greatly according to race, therefore
      we may say that general ethnic differences are more pronounced than gender
      related ones.

PMID- 15847382
TI  - Morphologic evaluation of radiotherapy in cervical carcinoma--a computerized
      morphometric approach.
AB  - Our work analyses the effects of radiotherapy in cervical carcinoma by
      computerized morphometry techniques that evaluate the morphologic changes in the
      specimens taken from pre and post-irradiation biopsies of 8 cases. These cases
      were diagnosed as squamous cell carcinoma, undifferentiated (1 case), moderately
      (5 cases) and well differentiated (2 cases). For each case, 40 relevant
      microscopic fields were chosen, reflecting the morphologic aspects before (20
      fields) and after irradiation (20 fields). The digitised images of these fields
      were used for measuring the tumoral and stromal areas by a program we implemented
      in the Zeiss KS400 environment. The program provides a mean tumoral/stromal area
      for each case, computed by averaging the results of the 20 measurements performed
      on the pre and post-irradiation images. In terms of a stereological
      interpretation, each mean tumoral area expresses the percentage of the tumoral
      volume and can be used as an index for quantifying the efficiency of the
      radiotherapy. Such an index allows developing comparative discussions on cases
      that belong either to the same diagnosis entity, or to different diagnosis
      entities. These discussions yield the idea that the morphologic classification of
      a case is not sufficient to accurately predict the efficiency of irradiation, and
      a systematic approach to the morphometric features, before and after irradiation,
      may contribute to the refinement of the prediction.

PMID- 15847383
TI  - The histopathological and immunohistochemical diagnosis in small cell lung
      carcinoma.
AB  - The small cells lung carcinoma (SCLC) represents 10-25% of the bronchogenical
      carcinomas, prevails at middle ages and is closely associated with tobacco smoke.
      It belongs to the group of carcinomas with neuroendocrine differentiation, the
      patients presenting various paraneoplastic syndromes. The study was performed on
      491 patients with a clinical and radiological suspicion of bronchopulmonary
      cancer. In this study, the histopathological examination gives results similar to
      those mentioned in the medical literature for the small cells lung carcinoma,
      prevailing in the case of young patients. The immunohistochemical examinations
      are particularly precious in confirming the diagnosis, especially in the
      diagnosis of the lymphonodular micrometastases.

PMID- 15847384
TI  - The immunohistochemical profile of luminal epithelial neoplastic component from
      pleomorphic adenomas of salivary glands.
AB  - The immunohistochemistry study made on 30 cases of salivary glands pleomorphic
      adenomas aims to establish the antigen profile of luminal epithelial neoplastic
      component proliferates into these tumors. We ascertain that luminal epithelial
      neoplastic cell were almost exclusively positive to antibody peculiar to
      epithelial differentiation (AE1/AE3, MNF 116, CK 8, CK 19, CK20, EMA) and
      occasional to S-100 protein and negative to vimentin, alpha-smooth muscle actin,
      calponin, Glial Fibrillary Acidic Protein (GFAP). This kind of immunoreactivity
      was similar to ductal cells from striated channels of salivary glands, suggesting
      the origin of such pleomorphic adenomas from this place.

PMID- 15847385
TI  - Evaluation of T-lymphocyte subtypes in the diagnosis of celiac disease.
AB  - The objectives of this study were to verify comparatively clinical age reported
      antecedents and the morphological aspect of the intestinal mucosa in patients
      sensitive to gluten, hospitalised at IOMC ("Alfred Russescu" Hospital) in the
      last 7 years. Celiac disease is an inflammation most frequently affecting the
      proximal small intestine, depending on the presence of gluten in the diet, whose
      pathogenesis seems to be immunological in nature. 107 cases were divided in three
      groups following clinical manifestations types at hospitalisation time: typical
      digestive, untypical digestive and extra digestive manifestations. Intestinal
      biopsies, made with Crosby probe, in children aged between 1.3 and 8 years (one
      single case was diagnosed as late as at the age of 15), regardless of gender.
      Then we analysed morphologically (HE usual and PAS histochemical staining) and
      immunohistochemically (lymphocytes B, T with possible subtypes). The lesions were
      counted at the first biopsy according to the Marsh score. The immunohistochemical
      tests have indicated the prevalence of T lymphocytes (UCHL1, CD3, CD4, CD8, gamma
      delta) both in the luminal epithelium with various degrees of aggression in
      lamina propria and also spread in stroma. B-lymphocytes (L26) are distributed
      prevalently nodular in stroma. In conclusion, it is CD4 T cells that are present
      in particular in the control of the gluten immune response in patients with Marsh
      I and Marsh III lesions.

PMID- 15847386
TI  - Histological study [correction of styudy] of the femural head and neck
      microscopic architecture in persons with senile osteoporosis.
AB  - For our study were available fragments of bony tissue from 24 patients (15
      females and 9 males) aged between 55-82 which needed hip arthroplasty after they
      had undergone femural neck fractures. Biologic pieces have been fixed, then
      decalcified and processed by wax embedding. We noted that the spongious osseous
      tissue appeared as rarefied after the remoulding processes; osseous traveas grew
      unplainly thinner, with their large areolar cavities filled of bony yellow
      marrow. The osseous cortex presented deformed osteomas with large irregular
      Havers ducts. The osteocytes appeared rarefied, of small size with a picnotic and
      hyperchrome nucleus.

PMID- 15847387
TI  - Value of immunohistochemistry in confirming undifferentiated ovarian carcinomas.
AB  - The present immunohistochemical study was carried out on ten cases of ovarian
      tumours diagnosed with usual staining as undifferentiated ovarian carcinomas. A
      panel of antibodies was chosen in order to confirm the epithelial origin of these
      tumours and to eliminate some possible ovarian metastasis. The cytokeratin
      AE1/AE3, EMA and BerEP4 positivity supported their epithelial origin even if
      thirty per cent of the cases co-expressed cytokeratin and vimentin. Even if there
      is not a specific marker to confirm the ovarian origin of the tumours, the CA125
      and CEA positivity suggested that these carcinomas might represent a serous or a
      mucinous dedifferentiation. Associated with these antibodies, the calretinin, CK7
      and CK20 stainings allowed the separation of these tumours from peritoneal
      mesotheliomas with ovarian extension and from ovarian metastasis originating in
      the gastrointestinal tract. The evaluation of the PCNA labelling index confirms
      the high degree of cell proliferation and the aggressiveness of these tumours.

PMID- 15847388
TI  - Histological and histochemical alteration in certain Black Sea bivalves submitted
      to accidental pollution.
AB  - Due to their microphage capacity, two-valve shells have great biologic
      importance: they clean the environment of harmful microorganisms and decaying
      organic compounds which result in water purification, water filtering by means of
      adaptive structures of digestive system and, indirectly, by those of respiratory,
      circulatory and excretive system is of major significance. Waste materials
      derived from animal metabolism coalesce in larger aggregates which sink and
      deposit onto the bottom, thus enabling the bivalvular shells to contribute to
      developing and securing adequate conditions for the productive cycle of marine
      environment and even twining themselves into food for animals. Our study makes a
      histological, histochemical and histometric survey of branchia (ctenidia) of
      Mytilus galloprovinciallis so as to enlarge the scant body of knowledge on the
      topic in reference literature.

PMID- 15847389
TI  - Overexpression of cytokeratin 34beta E12 in thymoma: could it be a poor prognosis
      factor?
AB  - We included in our study nine normal human thymuses and sixteen thymomas (1 type
      A, 2 type AB, 3 type B1, 3 type B2, 5 type B3 and 2 type C). The 25 patients were
      between 7 days and 75 years old, and were submitted to open surgery for
      correction of congenital heart defects or for mediastinal tumor mass. Biopsies
      were formalin fixed for 24 hours and then embedded in paraffin using routine
      procedure. Five micrometers step sections were mounted on silanized slides.
      Slides from each case were stained with haematoxylin and eosin method for
      morphological diagnosis. Additional sections were immunostained using monoclonal
      antibodies against high molecular weight cytokeratin clone 34beta E12. We found a
      very strong positive reaction for this type of cytokeratin in thymomas type B2,
      B3 and inconstant in type C comparative with normal thymus. Also, the number and
      distribution of positive epithelial cells in normal thymus versus thymomas were
      different. We found positive cells into capsular vessels of thymomas. This could
      be an invasion marker for apparent encapsulated thymomas. Strong positive
      reaction in almost all epithelial cells of thymomas types mentioned above was
      correlated in part with invasion. We concluded that expression of 34beta E12
      cytokeratin is a useful marker for thymomas with high grade of malignacy,
      correlated with vascular and capsular invasion.

PMID- 15847390
TI  - Histopathologic and immunohistochemical study in one case of cystadenoma of
      parotid gland becoming malignant.
AB  - Cystadenoma and cystadenocarcinoma of the salivary glands are rare tumors,
      approximately half of cases being diagnosed at the level of parotid. The studied
      tumor associated both benign and malign zones, with deep infiltrating character
      in the adjacent structures. In both areas the growing pattern was predominantly
      cystic and papillary, and the proliferated neoplastic cells were majority cubical
      or columnar, with low grade of nuclear pleomorphism in the becoming malign areas,
      discordant with the infiltrative character of the neoplasm.
      Immunohistochemically, we investigated the tumor with AE1-AE3, CEA, SMA, S-100
      and PCNA.

PMID- 15847391
TI  - Histologic and immunohistochemical study of the vascular and perivascular
      structures in patients with chronic obstructive bronchopneumopathy (COBP).
AB  - Histologic and immunohistochemical changes of the lung vascular and perivascular
      structures in 37 clinical and paraclinical COBP diagnosed were studied. We noted
      the deterioration of an important part of the pulmonary capillary network because
      of the destruction of interalveolar septae, with an intense vascular congestion
      within restant capillaries. The venules and arterioles have had a fibrosis wall
      by the replacing of the elastic and muscular fibers with inextensible fibers of
      collagen. The perivascular stroma was infiltrated by fibroblasts, macrophages,
      lymphocytes and plasma cells.

PMID- 15847392
TI  - Aspects of the cell population in the skin of the guinea pig exposed to
      hyperbaric-hyperoxic environment.
AB  - Knowing that in hyperbaric-hyperoxic environment, the production of free oxygen
      radicals is increased, with the direct implications on cellular metabolism, our
      study follows the influence of the hyperbaric environment, a very complex organ
      that is exposed to directly to this environment. We used a group of 10 guinea
      pigs split into to lots (test and control lots). The test lot was exposed for
      consecutive days to an ambient pressure of 6 ATM for a period of 30 min. After 50
      days both groups was given lethal doses of pentobarbital, afterwards skin was
      harvested and fixed into Bouin's fluid and formaline, than paraffin embedded. The
      slides stained with Haematoxylin-Eosin and trichromic Van Gieson. The epidermal
      fields examined by us revealed no significant variations of nuclear number,
      though the mean saturation of nuclei was significantly greater in test animals
      than in the control group, while the nuclear area fraction was higher in the
      control group. The melanin load of the epidermal cells was increased in the
      control animals. The presence of intraepidermal vacuoles was identified, their
      amount being almost double in test animals than in the control group.

PMID- 15847393
TI  - Histopathologic aspects in microglandular hyperplasia of endocervix.
AB  - In this study we analysed 373 cases of microglandular hyperplasia of endocervix
      belonging to patients from the III-VII decades of life. Most of the lesions had
      the typic aspect of proliferation of small glandular lumen lined by endocervix
      type epithelium, with or without areas of basal proliferation or immature
      squamous metaplasia. In 8 cases the growing patterns were peculiar, with mucinous
      or florid aspects, three of the cases rising differential diagnosis problems with
      cervical carcinoma.

PMID- 15847394
TI  - Comparative study between prostatic carcinoma G1-G3 and Gleason grading systems.
AB  - The need of an accurate and prognostically valuable method for grading the
      prostatic carcinoma resulted in, in the last decades, a large number of systems,
      none of them succeeding in being unanimously accepted by the pathologists family.
      The authors selected and reassessed using Gleason system a group of 221 cases
      with prostatic adenocarcinoma previously diagnosed using a combined G1-G3 system.
      The results were converted from Gleason system to G1-G3 system and then compared
      with the initial diagnostics. The group was divided, following the type of
      surgical procedure used for drawing the tissue, into three groups: transvesical
      prostatectomies (TVP), transurethral resections (TUR) and needle biopsies (B).
      The concordance between the two systems was good, even the number of TUR and B
      specimens was significant (85% of the studied group) showing that any of them can
      be successfully used in current practice, depending only on pathologist's
      experience.

PMID- 15847395
TI  - [Zn7{(2-C5H4N)CH(OH)PO3}6 (H2O)6]SO4 x 4H2O: a zinc phosphonate cluster with a
      drum-like cage structure.
AB  - Direct reaction of hydroxy(2-pyridyl)methylphosphonic acid with zinc sulfate
      under hydrothermal conditions results in the formation of the novel heptanuclear
      cluster compound [Zn7{(2-C5H4N)CH(OH)PO3}6 (H2O)6]SO4 x 4H2O (1). The inorganic
      core of the cluster can be described as a cylindrical drum made up of six Zn
      atoms bridged by six {CPO3} units that is centered by a seventh Zn atom. Crystal
      data: monoclinic, C2/c, a = 22.690(2) A, b = 16.675(2) A, c = 18.151(2) A, beta =
      93.390(2) degrees.

PMID- 15847396
TI  - Mica surfaces stabilize pentavalent uranium.
AB  - High-resolution X-ray photoelectron spectroscopy was used to demonstrate that
      reduction of aqueous U6+ at ferrous mica surfaces at 25 degrees C preserves U5+
      as the dominant sorbed species over a broad range of solution compositions.
      Polymerization of sorbed U5+ with sorbed U6+ and U4+ is identified as a possible
      mechanism for how mineral surfaces circumvent the rapid disproportionation of
      aqueous U5+. The general nature of this mechanism suggests that U5+ could play an
      important, but previously unidentified, role in the low-temperature chemistry of
      uranium in reducing, heterogeneous aqueous systems.

PMID- 15847397
TI  - Supramolecular recognition forces: an examination of weak metal-metal
      interactions in host-guest formation.
AB  - Molecular receptors consisting of two parallel-disposed terpy-M-Cl units (M =
      Pd2+, Pt2+) are used to form host-guest adducts with aromatic molecules and with
      neutral square-planar Pt2+ complexes. Host-guest formation is controlled by
      several factors including pi-pi interactions and, in some cases, weak Pt-Pt
      interactions between the host and the guest. This latter interaction was examined
      by comparing the host-guest stability of adducts formed by isoelectronic Pt2+ and
      Au3+ complexes with the Pt2+ receptor. Consistently, the former is more stable.

PMID- 15847398
TI  - Rb3In(H2O)Si5O13: a novel indium silicate with a CdSO4-topological-type
      structure.
AB  - A novel indium silicate, Rb3In(H2O)Si5O13, has been synthesized using a high
      temperature, high-pressure hydrothermal method and characterized by single
      crystal X-ray diffraction. The structure consists of five-membered rings of
      corner-sharing SiO4 tetrahedra connected via corner sharing to four adjacent five
      membered rings to form a 3D silicate framework that belongs to the CdSO4
      topological type. The InO6 octahedron shares five of its corners with five
      different SiO4 tetrahedra to form a 3D frame-work that delimits two types of
      channels to accommodate the rubidium cations. The sixth corner of InO6 is
      coordinated H2O. The structure is related to that of the titanium silicate ETS
      10, and these are the only two metal silicates that have the CdSO4-topological
      type structure. In addition, the crystal of Rb3In(H2O)Si5O13 shows an intense
      second harmonic generation signal. Crystal data: H2Rb3InSi5O14, monoclinic, space
      group Cc (No. 9), a = 9.0697(5) A, b = 11.5456(6) A, c = 13.9266(8) A, beta =
      102.300(1) degrees, V = 1424.8(1) A3, and Z = 4.

PMID- 15847399
TI  - An unprecedented coordination mode of the tris(pyrazolyl)methane donor set in
      {[Ph2(O)POCH2C(pz)3 Ag]2 (THF)2}(BF4)2: kappa2-kappa1 bimetallic, N(sigma)/N(pi)
      chelating.
AB  - The structure of the compound {[Ph2(O)POCH2C(pz)3 Ag]2 (THF)2}(BF4)2 (pz =
      pyrazolyl ring) revealed a new coordination mode for the tris(pyrazolyl)methane
      donor set: two pyrazolyl rings bridging the same two silvers atoms using normal
      sigma-type orbitals on the nitrogen donor atoms while the third pyrazolyl ring
      coordinates side-on to one of the silver atoms with a nitrogen-based pi-type
      orbital. The dimeric arrangement is also supported by a weak silver-silver
      interaction. This bonding description is supported by Fenske-Hall molecular
      orbital calculations.

PMID- 15847400
TI  - Metal-organic frameworks based on trigonal prismatic building blocks and the new
      "acs" topology.
AB  - Cationic and mixed-valent forms of Fe3O(CO2)6 trigonal prismatic clusters have
      been linked by ditopic links, namely, 1,4-benzenedicarboxylate (1,4-BDC) and 1,3
      benzenedicarboxylate (1,3-BDC), to produce two 3-periodic metal-organic
      frameworks (MOFs), [Fe3O(1,4-BDC)3 (DMF)3][FeCl4] x (DMF)3 (MOF-235) and Fe3O(1,3
      BDC)3 (py)3 x (py)0.5(H2O)1.5 (MOF-236) (DMF = N,N-dimethylformamide, py =
      pyridine), respectively. These MOFs exemplify a new, high-symmetry topology
      termed acs which we identify here as the default arrangement for linking trigonal
      prisms together.

PMID- 15847401
TI  - Synthesis, crystal structure, and properties of MnNCN, the first carbodiimide of
      a magnetic transition metal.
AB  - Synthesis, single-crystal structure determination, and magnetic properties are
      reported for manganese carbodiimide, MnNCN. The presumably unstable but inert
      phase adopts the trigonal system (R3m) with a = 3.3583(4) A, c = 14.347(2) A, V =
      140.13(3) A3, and Z = 3. Divalent manganese is octahedrally coordinated by
      nitrogen atoms at 2.26 A, and the NCN(2-) unit adopts the linear [N=C=N](2-)
      carbodiimide shape with two C=N double bonds of 1.23 A. MnNCN contains high-spin
      Mn(II) with five unpaired electrons and behaves like an antiferromagnet with an
      ordering temperature below 30 K.

PMID- 15847402
TI  - A surprisingly stable macrochelate formed from the reaction of cis dinuclear
      platinum antitumor compounds with reduced glutathione.
AB  - The structurally unique macrochelate [{Pt(en)}2-mu-{H2N(CH2)6 NH2}-mu-(SG)] (I)
      is the principal product of the reaction of the dinuclear compound [{PtCl(en)}2
      mu-{H2N(CH2)6 NH2}]Cl2 (1) with reduced glutathione (GSH) in a stoichiometric 1:1
      ratio in phosphate buffered saline (PBS) (pH 7.35). The macrochelate is formed
      through simultaneous bridging of the hexanediamine linker and glutathione
      thiolate. This represents a novel structure for glutathione adducts of platinum.
      At higher (1:4) ratios of Pt complex to GSH, an interesting interchange between
      bridged Pt-(SG)-Pt and terminal Pt-SG species is observed with the diamine linker
      still remaining intact in all cases. The integrity of I is further evident when
      reaction ratios are increased to 1:4 (Pt complex/GSH), and additional minor
      products are identified as [{Pt(en)SG}2-mu-{NH2(CH2)6 NH2}] (II), which
      transforms to [{Pt{NH2(CH2)2 NH2}(SG)}2-mu-{H2N(CH2)6 NH2}-mu-(SG)] (III), where
      the chelate ring is broken to produce a dangling monodentate ethylenediamine. The
      chemical shifts of the Pt-NH2 linker in all compounds are explained by
      consideration of the enhanced rigidity of the macrochelate (I) leading to
      shielding in comparison to the "open" monodentate structures (II, III). The
      remarkable stability of I is discussed in terms of possible biological
      implications.

PMID- 15847403
TI  - On the existence and stability of branched selenium chains: isomers of Me2Se3 and
      Et2Se3.
AB  - According to ab initio MO calculations at the G2(MP2) level of theory, branched
      isomers of dialkyl triselenides, R-Se(=Se)-Se-R (1; R = Me, Et), are less stable
      by more than 60 kJ mol(-1) than the isomeric unbranched chains R-Se-Se-Se-R (2).
      Therefore, species 1 cannot be generated in substantial concentrations under
      equilibrium conditions at moderate temperatures, as has recently been claimed by
      Meja and Caruso (Inorg. Chem. 2004, 43, 7486). Alternatively, the isomeric CH3-Se
      CH2-Se-Se-Et (3) can be considered to explain the reported gas chromatograms and
      mass spectra previously assigned to Et-Se(=Se)-Se-Et (1b). However, the
      isomerization 2b --> 3 is also endothermic, by deltaG(o)298 = 63 kJ mol(-1). The
      isomeric selenols HSe-C2H4-Se-Se-Et (4) and CH3-CH(SeH)-Se-Se-Et (5) are also
      less stable than 2b (by ca. 56 kJ mol(-1)), but 4 is another candidate to explain
      the mass spectrum formerly assigned to 1b. The calculated structures of 1-5 are
      reported.

PMID- 15847404
TI  - The first beta-diketiminate-Ag(I) complexes. Macrocyclic dinuclear and
      tetranuclear Ag(I)-complexes and linear coordination polymer Ag(I)-complex.
AB  - Reactions of Ag(I) and a series of beta-diketiminate ligands have been
      investigated to demonstrate that unique macrocyclic dinuclear and tetranuclear
      Ag(I)-complexes and a linear coordination polymer Ag(I)-complex as well as
      oxidative C-C coupling dimer products of the ligands were obtained depending on
      the substituents on the carbon framework of beta-diketiminate ligands.

PMID- 15847405
TI  - Ni-Pt multilayered nanowire arrays with enhanced coercivity and high remanence
      ratio.
AB  - Highly ordered Ni-Pt multilayered nanowire arrays have been fabricated using a
      porous anodic aluminum oxide (AAO) template by pulse electrodeposition. The
      cylindrical Ni nanoparticles with different lengths and diameters in these arrays
      were characterized by transmission electron microscope (TEM) and alternating
      gradient magnetometer (AGM) measurements. Magnetization measurements revealed
      that an array of such nanowires with 20-nm diameters has an enhanced coercivity
      (ca. 1169 Oe) and a high remanence ratio (ca. 0.96).

PMID- 15847406
TI  - Reduction pathway of end-on terminally coordinated dinitrogen. IV. Geometric,
      electronic, and vibrational structure of a W(IV) dialkylhydrazido complex and its
      two-electron-reduced derivative undergoing N-N cleavage upon protonation.
AB  - The molybdenum and tungsten dialkylhydrazido complexes [M(dppe)2 (NNC5H10)]2+ (M
      = Mo, W; compounds A(Mo) and A(W)) and their two-electron-reduced counterparts
      [M(dppe)2 (NNC5H10)] (compounds B(Mo) and B(W)) are characterized structurally
      and spectroscopically. The crystal structure of B(W) indicates a geometry between
      square pyramidal and trigonal bipyramidal with the NNC5H10 group in the apical
      position and in the trigonal plane of the complex, respectively. Temperature
      dependent 31P NMR spectra of B(Mo) show that this geometry is present in solution
      as well. At room temperature, rapid Berry pseudorotation between the "axial" and
      "equatorial" ligand positions gives rise to a singlet in the 31P NMR spectrum.
      This exchange process is slowed at low temperature, leading to a doublet. The N-N
      distance of B(W) is 1.388 A, and the W-N distance is 1.781 A. Infrared and Raman
      spectroscopy applied to A(W), B(W), and their 15N isotopomers reveals extensive
      mixing between the N-N and W-N vibrations of the metal-N-N core with the modes of
      the piperidine ring. The N-N force constant of A(W) is determined to be 6.95
      mdyn/A, which is close to the values of the Mo and W NNH2 complexes. In B(W), the
      N-N force constant decreases to 6.4 mdyn/A, which is between the values found for
      the Mo/W NNH3 and NNH2 complexes. This allows us to attribute N-N double bond
      character to A(W) and intermediate character between the double and single bonds
      for the N-N bond of B(W). These findings are supported by DFT calculations. More
      importantly, the HOMO of B(W) corresponds to a linear combination of the metal
      d(sigma) orbital with a ligand orbital having N-N sigma* character, inducing a
      weakening of the N-N bond. This contributes to the cleavage of the N-N bond
      taking place upon protonation of B(W) at the Nbeta atom of the NNC5H10 group.

PMID- 15847407
TI  - Reduction pathway of end-on terminally coordinated dinitrogen. V. N-N bond
      cleavage in Mo/W hydrazidium complexes with diphosphine coligands. Comparison
      with triamidoamine systems.
AB  - N-N cleavage of the dialkylhydrazido complex [W(dppe)2(NNC5H10)] (B(W)) upon
      treatment with acid, leading to the nitrido/imido complex and piperidine, is
      investigated experimentally and theoretically. In acetonitrile and at room
      temperature, B(W) reacts orders of magnitude more rapidly with HNEt3BPh4 than its
      Mo analogue, [Mo(dppe)2(NNC5H10)] (B(Mo)). A stopped-flow experiment performed
      for the reaction of B(W) with HNEt3BPh4 in propionitrile at -70 degrees C
      indicates that protonation of B(W) is completed within the dead time of the
      stopped-flow apparatus, leading to the primary protonated intermediate B(W)H+.
      Propionitrile coordination to this species proceeds with a rate constant
      k(obs(1)) of 1.5 +/- 0.4 s(-1), generating intermediate RCN-B(W)H+ (R = Et) that
      rapidly adds a further proton at Nbeta and then mediates N-N bond splitting in a
      slower reaction (k(obs(2)) = 0.35 +/- 0.08 s(-1), 6 equiv of acid). k(obs(1)) and
      k(obs(2)) are found to be independent of the acid concentration. The
      experimentally observed reactivities of B(Mo) or B(W) with acids in nitrile
      solvents are reproduced by DFT calculations. In particular, geometry optimization
      of models of solvent-coordinated, Nbeta-protonated intermediates is found to lead
      spontaneously to separation into the nitrido/imido complexes and
      piperidine/piperidinium, corresponding to activationless heterolytic N-N bond
      cleavage processes. Moreover, DFT indicates a spontaneous cleavage of nonsolvated
      B(W) protonated at Nbeta. In the second part of this article, a theoretical
      analysis of the N-N cleavage reaction in the Mo(III) triamidoamine complex
      [HIPTN3N]Mo(N2) is presented (HIPTN3N = hexaisopropylterphenyltriamidoamine). To
      this end, DFT calculations of the Mo(III)N2)triamidoamine complex and its
      protonated and reduced derivatives are performed. Calculated structural and
      spectroscopic parameters are compared to available experimental data. N-N
      cleavage most likely proceeds by one-electron reduction of the Mo(V) hydrazidium
      intermediate [HIPTN3N]Mo(NNH3)+, which is predicted to have an extremely
      elongated N-N bond. From an electronic-structure point of view, this reaction is
      analogous to that of Mo/W hydrazidium complexes with diphos coligands. The
      general implications of these results with respect to synthetic N2 fixation are
      discussed.

PMID- 15847408
TI  - Concentration of carbon dioxide by electrochemically modulated complexation with
      a binuclear copper complex.
AB  - The reactions of bicarbonate ion with a series of binuclear Cu(II) complexes in
      buffered aqueous solution have been studied, and effective binding constants for
      bicarbonate have been determined at pH 7.4 for the complexes [Cu2(taec)]4+ (taec
      = N,N',N'',N'''-tetrakis(2-aminoethyl)-1,4,8,11-tetraazacyclotetradecane) and
      [Cu2(tpmc)(OH)]3+ (tpmc = N, N',N'',N'''-tetrakis(2-pyridylmethyl)-1,4,8,11
      tetraazacyclotetradecane). [Cu2(o-xyl-DMC2)]4+ (o-xyl-DMC2 = alpha,alpha'-bis(5,7
      dimethyl-1,4,8,11-tetraazacyclotetradecan-6-yl)-o-xylene) did not react with
      bicarbonate ion in an aqueous solution buffered at this pH. The complexes were
      reduced by controlled-potential electrolysis, and the stability of the Cu(I)
      derivatives in aqueous solution and their affinity for bicarbonate/carbonate ion
      were investigated. On the basis of these fundamental studies, [Cu2(tpmc)(mu
      OH)]3+ has been identified as an air-stable, water-soluble carrier for the
      capture and concentration of CO2 by electrochemically modulated complexation. The
      carrier binds to the carbonate ion strongly in its oxidized, Cu(II) form and
      releases the ion rapidly when reduced to the Cu(I) complex. In small-scale
      electrochemical pumping experiments designed to demonstrate the feasibility of
      this approach, CO2 has been pumped from an initial 10% CO2/N2 mixture up to a
      final concentration of 75%.

PMID- 15847409
TI  - Metal-rich chalcogenides. Synthesis, structure, and bonding of the layered
      Lu11Te4. Comparison with the similar Sc8Te3 and Ti11Se4.
AB  - The high-yield synthesis of Lu11Te4 by reaction of the components and annealing
      at 1200 degrees C is described. The structure determined by single-crystal
      diffraction means is monoclinic C2/m, Z = 6, a = 30.412(3) A, b = 3.9504(4) A, c
      = 21.073(2) A, beta = 102.96 degrees and consists of two independent condensed
      puckered sheets of Lu separated by individual Te atoms. Notwithstanding, the
      geometric structure is closely related to but distinctly different from those of
      both Sc8Te3 and Ti11Se4 (also C2/m), principally through displacements of pairs
      of atoms (the structure of the last was determined by electron diffraction).
      Further, close electronic similarities among the three structures are
      demonstrated by EHTB results in terms of both effective atom charge and bond
      overlap population trends between equivalent positions or functions.

PMID- 15847410
TI  - New Materials Derived from Ybco: CrSr2RECu2O8 (RE = La, Pr, Nd, Eu, Gd, Tb, Dy,
      Y, Ho, Er, Lu).
AB  - Eleven new oxides, derived from yttrium barium copper oxide by replacing the
      square-planar copper [Cu-O4] of the basal plane of the triple perovskite-based
      structure with octahedral Cr(IV), have been prepared at high pressure and
      temperature. Their crystal structures have been determined, and their complex
      microstructure has been established by means of high-resolution electron
      microscopy and electron diffraction. The materials have a general formula of
      CrSr2RECu2O8 (RE = La, Pr, Nd, Eu, Gd, Tb, Dy, Y, Ho, Er, and Lu); they are
      tetragonal, show the symmetry of space group P4/mmm, and do not appear to be
      superconducting.

PMID- 15847411
TI  - A phenolate-induced trans influence: crystallographic evidence for unusual
      asymmetric coordination of an alpha-diimine in ternary complexes of iron(III)
      possessing biologically relevant hetero-donor N-centered tripodal ligands.
AB  - Three mononuclear ternary complexes of iron(III) with an alpha-diimine (bipy or
      phen) and a derivative of N,N-bis(2-hydroxybenzyl)glycinate (L3-) have been
      synthesized and characterized by magnetic susceptibility measurements, electron
      paramagnetic resonance (EPR) spectroscopy, vibrational spectroscopy, and
      electronic absorption spectroscopy. Single-crystal X-ray structure determinations
      of the pseudo-octahedral complexes [Fe(bipy)L] x MeCN [L = (3,5-Br2)-L3- or (5,3
      Cl,Me)-L3-] revealed a considerable and consistent distortion in the coordination
      of bipy to iron(III) attributable largely to electronic effects. In both crystal
      structures, the Fe-N(pyridyl) bond trans to the phenolate oxygen is 0.133 A
      longer than the other one positioned trans to the tertiary amine nitrogen, a
      relatively weaker donor. This coordination behavior of bipy is of structural
      interest and has not been observed previously for iron(III). The electronic and
      EPR spectra of the compounds [Fe(L'-L')L] x MeCN (L'-L' = bipy or phen) are
      consistent with the spin state of the central metal atom (S = 5/2). The charge
      transfer transitions arising from the strong interactions of the phenolate
      moieties with the ferric ion have been identified as phenolate (p(pi)) -->
      iron(III) (d(pi*)) (lambda(max) approximately 500 nm, epsilon approximately 3000
      M(-1) cm(-1)) and phenolate (p(pi)) --> iron(III) (d(sigma*) (lambda(max)
      approximately 320 nm, epsilon approximately 5200 M(-1) cm(-1)). The presence of
      the phenolate moieties in the quadridentate hetero-donor tripodal ligands, H3L,
      lends these iron(III) ternary complexes the potential to model the specific metal
      coordination, metal-substrate interactions, and physicochemical behaviors of
      several iron-tyrosinate proteins.

PMID- 15847412
TI  - Synthesis and structure of K+ [iPrN=C=P]-, a 1-aza-3lambda3-phospha-3-allenide.
AB  - 2-Isopropyl(trimethylsilyl)amino-1lambda3-phosphaalkyne 1 reacts with potassium
      tert-butoxide to form potassium 1-isopropyl-1-aza-3lambda3-phospha-3-allenide
      (2). This compound was structurally characterized as the corresponding 18-crown-6
      ether complex 3. The molecular structure of 1 was also determined in order to
      compare the bonding situation in the anion and the neutral lambda3-phosphaalkyne.
      Compound 3 contains a nitrogen-carbon-phosphorus group for which the parameters
      were shown by X-ray structural analysis and quantum chemical calculations to lie
      between the extrema N-C[triple bond]P and N=C=P, suggesting reactivity typical of
      an ambident anion. This is indeed the case, as subsequent reaction of 2 with
      chlorotrimethylsilane at nitrogen regenerates the lambda3-phosphaalkyne 1; with
      chlorotriphenylsilane the new derivative 4 is formed. In contrast,
      chlorotrimethylstannane reacts at phosphorus, giving the 1-aza-3lambda3
      phosphaallene isopropyliminomethylidene(trimethylstannyl)phosphane 5.

PMID- 15847413
TI  - Synthesis, crystal structure, magnetic properties, and electronic structure of
      the new ternary vanadate CuMnVO4.
AB  - A new magnetic oxide, CuMnVO4, was prepared, and its crystal structure was
      determined by single-crystal X-ray diffraction. The magnetic properties of
      CuMnVO4 were characterized by magnetic susceptibility and specific heat
      measurements, and the spin exchange interactions of CuMnVO4 were analyzed on the
      basis of spin-polarized electronic band structure calculations. CuMnVO4 contains
      MnO4 chains made up of edge-sharing MnO6 octahedra containing high-spin Mn2+
      cations. Our work shows that CuMnVO4 undergoes a three-dimensional
      antiferromagnetic transition at approximately 20 K. Both the intrachain and
      interchain spin exchanges are antiferromagnetic, and the interchain spin exchange
      is not negligible compared to the intrachain spin exchange.

PMID- 15847414
TI  - Synthesis and spectroscopic and X-ray structural characterization of R2Sn(IV)
      oxydiacetate and -iminodiacetate complexes.
AB  - Seven novel R2Sn(IV)-oxydiacetate (oda) and -iminodiacetate (ida) compounds of
      the form [R2Sn(oda)(H2O)]2 (R = Me, nBu, and Ph) (1-3), [(R2SnCl)2(oda)(H2O)2]n
      (R = Et, iBu, and tBu) (4-6), and [Me2Sn(ida)(MeOH)]2 (7) have been synthesized
      and characterized by IR, 1H, 13C, and 119Sn NMR (solution), solid-state 119Sn
      CPMAS NMR, and (119m)Sn Mossbauer spectroscopy. The crystal structure of
      [Me2Sn(oda)(H2O)]2, 1, shows it to be dinuclear (centrosymmetric), with two seven
      coordinated tin atoms, bridged by one arm of the carboxylate group from each oda.
      By contrast, the crystal structure of [(Et2SnCl)2(oda)(H2O)2]n, 4, comprises a
      zigzag polymeric assembly containing a pair of different alternating subunits,
      {Et2SnCl(H2O)} and {Et2SnCl(H2O)(oda)}, which are connected by way of bridging
      oda carboxylates, thus giving seven-coordinate tin centers in both components.
      Finally, the structure of [Me2Sn(ida)(MeOH)]2, 7, also centrosymmetric dinuclear,
      is comprised of a pair of mononuclear units with seven-coordinate tin. The 119Sn
      solid-state CPMAS NMR and (119m)Sn Mossbauer suggest the presence of seven
      coordinate Sn metal atoms in some derivatives and the existence of two different
      tin sites in the [(R2SnCl)2(oda)(H2O)2]n compounds.

PMID- 15847415
TI  - Square planar vs tetrahedral geometry in four coordinate iron(II) complexes.
AB  - The geometric preferences of a family of four coordinate, iron(II) d6 complexes
      of the general form L2FeX2 have been systematically evaluated. Treatment of
      Fe2(Mes)4 (Mes = 2,4,6-Me3C6H2) with monodentate phosphine and phosphite ligands
      furnished square planar trans-P2Fe(Mes)2 derivatives. Identification of the
      geometry has been accomplished by a combination of solution and solid-state
      magnetometry and, in two cases (P = PMe3, PEt2Ph), X-ray diffraction. In
      contrast, both tetrahedral and square planar coordination has been observed upon
      complexation of chelating phosphine ligands. A combination of crystallographic
      and magnetic susceptibility data for (depe)Fe(Mes)2 (depe = 1,2
      bis(diethylphosphino)ethane) established a tetrahedral molecular geometry whereas
      SQUID magnetometry and Mossbauer spectroscopy on samples of (dppe)Fe(Mes)2 (dppe
      = 1,2-bis(diphenylphosphino)ethane) indicated a planar molecule. When dissolved
      in chlorinated solvents, the latter compound promotes chlorine atom abstraction,
      forming tetrahedral (dppe)Fe(Mes)Cl and (dppe)FeCl2. Ligand substitution
      reactions have been studied for both structural types and are rapid on the NMR
      time scale at ambient temperature.

PMID- 15847416
TI  - Esterase-activated two-fluorophore system for ratiometric sensing of biological
      zinc(II).
AB  - Intracellular ester hydrolysis by cytosolic esterases is a common strategy used
      to trap fluorescent sensors within the cell. We have prepared analogues of Zinpyr
      1 (ZP1), an intensity-based fluorescent sensor for Zn2+, that are linked via an
      amido-ester or diester moiety to a calibrating fluorophore, coumarin 343. These
      compounds, designated Coumazin-1 and -2, are nonpolar and are quenched by
      intramolecular interactions between the two fluorophores. Esterase-catalyzed
      hydrolysis generates a Zn2+-sensitive ZP1-like fluorophore and a Zn2+-insensitive
      coumarin as a calibrating fluorophore. Upon excitation of the fluorophores,
      coumarin 343 emission relays information concerning sensor concentration whereas
      ZP1 emission indicates the relative concentration of Zn2+-bound sensor. This
      approach enables intracellular monitoring of total sensor concentration and
      provides a ratiometric system for sensing biological zinc ion.

PMID- 15847417
TI  - Salt-inclusion synthesis of two new polar solids, Ba6Mn4Si12O34Cl3 and
      Ba6Fe5Si11O34Cl3.
AB  - A new family of salt-containing, mixed-metal silicates (CU-14), Ba6Mn4Si12O34Cl3
      (1) and Ba6Fe5Si11O34Cl3 (2), was synthesized via the BaCl2 salt-inclusion
      reaction. These compounds crystallize in the noncentrosymmetric (NCS) space group
      Pmc2(1) (No. 26), adopting 1 of the 10 NCS polar, nonchiral crystal classes, mm2
      (C2v). The cell dimensions are a = 6.821(1) A, b = 9.620(2) A, c = 13.172(3) A,
      and V = 864.4(3) A3 for 1 and a = 6.878(1) A, b = 9.664(2) A, c = 13.098(3) A,
      and V = 870.6(3) A3 for 2. The structures form a composite framework made of the
      (M(4+x)Si(12-x)O34)9- (M = Mn, x = 0; M = Fe, x = 1) covalent oxide and
      (Ba6Cl3)9+ ionic chloride sublattices. The covalent framework exhibits a pseudo
      one-dimensional channel where the extended barium chloride lattice
      (Ba3Cl1.5)(infinity) resides, and it consists of fused eight-membered meta
      silicate rings propagating along [100] via sharing two opposite [Si2O7]6- units
      to form an acentric lattice. Single-crystal structure studies also reveal the
      ClBa4 unit adopting an interesting seesaw configuration, in which the lone pair
      electrons of chlorine preferentially face the oxide anions of the transition
      metal silicate channel, thus forming the observed polar frameworks. Similar to
      the synthesis of organic-inorganic hybrid materials, the salt-inclusion method
      facilitates a promising approach for the directed synthesis of special framework
      solids, including NCS compounds, via composite lattices.

PMID- 15847418
TI  - Solution calorimetric and stopped-flow kinetic studies of the reaction of
      *Cr(CO)3C5Me5 with PhSe-SePh and PhTe-TePh. Experimental and theoretical
      estimates of the Se-Se, Te-Te, H-Se, and H-Te bond strengths.
AB  - The kinetics of the oxidative addition of PhSeSePh and PhTeTePh to the stable 17
      electron complex *Cr(CO)3C5Me5 have been studied utilizing stopped-flow
      techniques. The rates of reaction are first-order in each reactant, and the
      enthalpy of activation decreases in going from Se (deltaH(double dagger) = 7.0 +/
      0.5 kcal/mol, deltaS(double dagger) = -22 +/- 3 eu) to Te (deltaH(double dagger)
      = 4.0 +/- 0.5 kcal/mol, deltaS(double dagger) = -26 +/- 3 eu). The kinetics of
      the oxidative addition of PhSeH and *Cr(CO)3C5Me5 show a change in mechanism in
      going from low (overall third-order) to high (overall second-order) temperatures.
      The enthalpies of the oxidative addition of PhE-EPh to *Cr(CO)3C5Me5 in toluene
      solution have been measured and found to be -29.6, -30.8, and -28.9 kcal/mol for
      S, Se, and Te, respectively. These data are combined with enthalpies of
      activation from kinetic studies to yield estimates for the solution-phase PhE-EPh
      bond strengths of 46, 41, and 33 kcal/mol for E = S, Se, and Te, respectively.
      The corresponding Cr-EPh bond strengths are 38, 36, and 31 kcal/mol. Two methods
      have been used to determine the enthalpy of hydrogenation of PhSeSePh in toluene
      on the basis of reactions of HSPh and HSePh with either *Cr(CO)3C5Me5 or 2
      pyridine thione. These data lead to a thermochemical estimate of 72 kcal/mol for
      the PhSe-H bond strength in toluene solution, which is in good agreement with
      kinetic studies of H atom transfer from HSePh at higher temperatures. The
      reaction of H-Cr(CO)3C5Me5 with PhSe-SePh is accelerated by the addition of a Cr
      radical and occurs via a rapid radical chain reaction. In contrast, the reaction
      of PhTe-TePh and H-Cr(CO)3C5Me5 does not occur at any appreciable rate at room
      temperature, even in the presence of added Cr radicals. This is in keeping with a
      low PhTe-H bond strength blocking the chain and implies that H-TePh < or = 63
      kcal/mol. Structural data are reported for PhSe-Cr(CO)3C5Me5 and PhS
      Cr(CO)3C5Me5. The two isostructural complexes do not show signs of an increase in
      steric strain in terms of metal-ligand bonds or angles as the Cr-EPh bond is
      shortened in going from Se to S. Bond strength estimates of the PhE-H and PhE-EPh
      derived from density functional theory calculations are in reasonable agreement
      with experimental data for E = Se but not for E = Te. The nature of the singly
      occupied molecular orbital of the *EPh radicals is calculated to show increasing
      localization on the chalcogenide atom in going from S to Se to Te.

PMID- 15847419
TI  - The gas phase structure of ethynylferrocene using microwave spectroscopy.
AB  - Gas phase structural parameters for ethynylferrocene have been determined using
      microwave spectroscopy. Rotational transitions due to a- and b-type dipole
      moments were measured. Twenty four rotational constants have been determined by
      fitting the measured transitions of various isotopomers using a rigid rotor
      Hamiltonian with centrifugal distortion constants. Least-squares fits to
      determine structural parameters and Kraitchman analyses have been used to
      determine the gas phase structural parameters and the atomic coordinates from the
      rotational constants. The distance between the Fe atom and the C atoms of the
      cyclopentadienyl rings is r(Fe-C1) = 2.049(5) A, and the distance between the
      carbon atoms of the cyclopentadienyl ring is r(C-C) = 1.432(2) A. The ethynyl
      group is bent away from the Fe atom and out of the plane of the carbon atoms in
      the adjacent cyclopentadienyl ring by 2.75(6) degrees. Structural parameters were
      also obtained from DFT calculations and Kraitchman analyses, and the results are
      compared. Analysis of fit results for 13C isotopic substitution data indicates
      that the carbon atoms of the two cyclopentadienyl rings are in an eclipsed
      conformation in the ground vibrational state. Trends in microwave experimental
      values for the distance from the Fe atom to the center of the cyclopentadienyl
      ring for a series of substituted ferrocenes have been analyzed. This analysis
      provides an estimate of the gas phase distance from the Fe atom to the centers of
      the cyclopentadienyl rings for ferrocene of 1.65(1) A.

PMID- 15847420
TI  - Well-resolved, new water morphologies obtained by modification of the
      hydrophilic/hydrophobic character and shapes of the supporting layers.
AB  - The planar coordination complexes [Ag2L2] (L = ophen or obpy, where Hophen = 1H
      [1,10]phenanthrolin-2-one and Hobpy = 1H-[2,2']bipyridinyl-6-one) contain both
      hydrophilic and hydrophobic functional groups. Crystallization of these
      structurally related complexes in an aqueous medium gives [Ag2(ophen)2]2 x 6H2O
      (1), [Ag2(obpy)2]3 x 18H2O (2), and [Ag2(obpy)2]2 x 14.5H2O (3). Novel water
      morphologies are observed in these crystalline hydrates, similar 2D metal-organic
      layers in which the planar [Ag2L2] complexes as building blocks are stacked
      alternately together and provide hydrogen bond acceptor sites (O atoms) for
      anchoring 1D water chains or 2D water layers on their surfaces. In the wavelike
      metal-organic framework of 1, the wide hydrophobic region renders the formation
      of 1D water tapes containing four- and six-membered water rings, whereas more
      complex 2D water layers are sandwiched in 2 and 3, owing to the fact that the
      surfaces of the supporting layers are more hydrophilic than 1.

PMID- 15847421
TI  - Relationship between the ratio of ligand to metal and the coordinating ability of
      anions. Synthesis and structural properties of AgX-bearing bis(4
      pyridyl)dimethylsilane (X- = NO2-, NO3-, CF3SO3-, and PF6-).
AB  - Studies of the anion effects on the molecular construction of a series of AgX
      complexes with bis(4-pyridyl)dimethylsilane (L) (X- = NO2-, NO3-, CF3SO3-, and
      PF6-) have been carried out. Formation of the skeletal bonds appears to be
      primarily associated with a suitable combination of bidentate N-donors of L and a
      variety of coordination geometries of Ag(I) ions. The L:Ag(I) ratios of the
      products are dependent on the nature of the polyatomic anions. The 1:1 adduct
      Ag(I)-L for NO2-, 3:4 adduct for NO3-, 2:3 adduct for CF3SO3-, and 1:2 adduct for
      PF6- have been obtained. A linear relationship between the ratio of ligand to
      metal and the coordinating ability of anions was observed. [Ag(NO2)(L)] has a
      unique sheet structure consisting of double helices, and [Ag3(L)4](NO3)3 is a 2
      nm thick interwoven sheet structure consisting of nanotubes. The compound
      [Ag2(L)3](CF3SO3)2 affords a characteristic ladder-type channel structure, and
      [Ag(L)2](PF6) is a simple 2D grid structure.

PMID- 15847422
TI  - Coordination polymers of La(III) as bunched infinite nanotubes and their
      conversion into an open-framework structure.
AB  - Pyridine-2,6-dicarboxylic acid (pdcH2) reacts with LaCl3 x 7H2O under
      hydrothermal conditions followed by evaporation at room temperature to give a
      metal-organic framework structure of the empirical formula, [La(pdc)(H2O)4] x Cl
      (1), in the form of infinitely long bunched nanotubes. The chloride ions and
      water molecules occupy the tubular as well as the inter-tubular spaces. When
      La(NO3)3 x 7H2O is used in place of LaCl3 x 6H2O, a similar structure is formed
      with the empirical formula, [La(pdc)(H2O)4] x NO3 (2), where water molecules and
      the nitrate anions occupy the voids as in the case of 1. When an aqueous solution
      of AgNO3 is added to an aqueous solution of 1, the Cl- ions are replaced
      completely by NO3- ions to form 2; thus, the tubular structure is conserved.
      However, when AgBF4 is used in place of AgNO3, the tubular structure breaks down,
      and a new 3-D MOF structure, [La(pdc)(pdcH)(H2O)2] x 4H2O (3), is formed where
      the cavities are occupied by hexameric and dimeric water clusters. Structure 3 is
      also formed as the sole product when La(OAc)3 x xH2O is treated with pyridine-2,6
      dicarboxylic acid following the method adopted for 1 and 2. Formation of the
      tubular structure depends on the molar ratio of the ligand and the metal. When
      higher than 1 equiv of the metal is taken, a linear coordination polymer,
      [La2(pdc)3(H2O)6] x 2H2O (4), is formed. This study provides the first
      nanotubular structure of a pure lanthanide metal.

PMID- 15847423
TI  - Dihydrogen complexes of rhodium: [RhH2(H2)x (PR3)2]+ (R = Cy, iPr; x = 1, 2).
AB  - Addition of H2 (4 atm at 298 K) to [Rh(nbd)(PR3)2][BAr(F)4] [R = Cy, iPr] affords
      Rh(III) dihydride/dihydrogen complexes. For R = Cy, complex 1a results, which has
      been shown by low-temperature NMR experiments to be the bis-dihydrogen/bis
      hydride complex [Rh(H)2(eta2-H2)2(PCy3)2][BAr(F)4]. An X-ray diffraction study on
      1a confirmed the {Rh(PCy3)2} core structure, but due to a poor data set, the
      hydrogen ligands were not located. DFT calculations at the B3LYP/DZVP level
      support the formulation as a Rh(III) dihydride/dihydrogen complex with cis
      hydride ligands. For R = iPr, the equivalent species, [Rh(H)2(eta2-H2)2(P
      iPr3)2][BAr(F)4] 2a, is formed, along with another complex that was
      spectroscopically identified as the mono-dihydrogen, bis-hydride solvent complex
      [Rh(H)2(eta2-H2)(CD2Cl2)(P iPr3)2][BAr(F)4] 2b. The analogous complex with PCy3
      ligands, [Rh(H)2(eta2-H2)(CD2Cl2)(PCy3)2][BAr(F)4] 1b, can be observed by
      reducing the H2 pressure to 2 atm (at 298 K). Under vacuum, the dihydrogen
      ligands are lost in these complexes to form the spectroscopically characterized
      species, tentatively identified as the bis hydrides [Rh(H)2(L)2(PR3)2][BAr(F)4]
      (1c R = Cy; 2c R = iPr; L = CD2Cl2 or agostic interaction). Exposure of 1c or 2c
      to a H2 atmosphere regenerates the dihydrogen/bis-hydride complexes, while adding
      acetonitrile affords the bis-hydride MeCN adduct complexes
      [Rh(H)2(NCMe)2(PR3)2][BAr(F)4]. The dihydrogen complexes lose [HPR3][BAr(F)4] at
      or just above ambient temperature, suggested to be by heterolytic splitting of
      coordinated H2, to ultimately afford the dicationic cluster compounds of the type
      [Rh6(PR3)6(mu-H)12][BAr(F)4]2 in moderate yield.

PMID- 15847424
TI  - Rhenium(V) and technetium(V) complexes with phosphoraneimine and
      phosphoraneiminato ligands.
AB  - Air-stable rhenium(V) nitrido complexes are formed when [ReOCl3(PPh3)2],
      [NBu4][ReOCl4], or [NBu4][ReNCl4] are treated with an excess of silylated
      phosphoraneiminates of the composition Me3SiNPPh3 or Ph2P(NSiMe3)CH2PPh2 in
      CH2Cl2. Complexes of the compositions [ReNCl(Ph2PCH2PPh2NH)2]Cl (1),
      [ReN(OSiMe3)(Ph2PCH2PPh2NH)2]Cl (2) or [ReNCl2(PPh3)2] (3) were isolated and
      structurally characterized. The latter compound was also produced during a
      reaction of the rhenium(III) precursor [ReCl3(PPh3)2(CH3CN)] and Me3SiNPPh3.
      Nitrogen transfer from the phosphorus to the rhenium atoms and the formation of
      nitrido ligands were observed in all examples. All products of reactions with an
      excess of the potentially chelating phosphoraneiminate Me3SiNP(Ph2)CH2PPh2
      contain neutral Ph2PCH2PPh2NH ligands. The required protons are supplied by a
      metal-induced decomposition of the solvent dichloromethane. The Re-N(imine) bond
      lengths (2.055-2.110 A) indicate single bonds, whereas the N-P bond with lengths
      between 1.596 A and 1.611 A reflect considerable double bond character. An
      oxorhenium(V) phosphoraneiminato complex, the dimeric compound [ReOCl2(mu-N
      Ph2PCH2PPh2N)]2 (4), is formed during the reaction of [NBu4][ReOCl4] with an
      equivalent amount of Ph2P(NSiMe3)CH2PPh in dry acetonitrile. The blue neutral
      complex with two bridging phosphoraneiminato units is stable as a solid and in
      dry solvents. It decomposes in solution, when traces of water are present. The
      rhenium-nitrogen distances of 2.028(3) and 2.082(3) A are in the typical range of
      bridging phosphoraneiminates and an almost symmetric bonding mode. Technetium
      complexes with phosphoraneimine ligands were isolated from reactions of
      [NBu4][TcOCl4] with Me3SiNPPh3, and [NBu4][TcNCl4] with Me3SiNP(Ph2)CH2PPh2.
      Nitrogen transfer and the formation of a five-coordinate nitrido species,
      [TcNCl2(HNPPh3)2] (5), was observed in the case of the oxo precursor, whereas
      reduction of the technetium(VI) starting material and the formation of the
      neutral technetium(V) complex [TcNCl2(Ph2PCH2PPh2NH)] (6) or
      [TcNCl(Ph2PCH2PPh2NH)2]Cl (7) was observed in the latter case. Both technetium
      complexes are air stable and X-ray structure determinations show bonding modes of
      the phosphoraneimines similar to those in the rhenium complexes.

PMID- 15847425
TI  - High-nuclearity mixed-chelate ferric complexes from a new family of polynuclear
      precursors.
AB  - The syntheses, structures, and magnetochemical characterization of two novel
      mixed-chelate undeca- and dodecanuclear ferric complexes are reported. Preformed
      tri- and pentanuclear ferric complexes that possess tridentate Schiff base (L2-
      and (L'2-) and acetate ligands were reacted with 1,1,1-tris(hydroxymethyl)ethane
      (H3thme) to afford [Fe11O3(OH)(O2CMe)8(thme)2(L)6] (1) and
      [Fe12O4(O2CMe)8(thme)2(NH2(CH2)2O)2(L')6] (2), respectively, following structural
      agglomeration and rearrangement associated with ligand substitution. The
      incorporation of more than one type of ligand that can both chelate and bridge
      the Fe centers gives rise to the complicated molecular structures displayed by 1
      and 2. As a result of the tripodal conformation of thme3-, the cores of both
      molecules incorporate several face-shared defect {Fe3O4}+ cuboidal subunits.
      Variable-temperature dc and ac magnetic susceptibility studies, together with low
      temperature magnetization measurements, are consistent with S = 5/2 and S = 0
      ground-state spins for 1 and 2, respectively, and suggest that excited states
      with higher spin values lie relatively close in energy to the ground state for
      both species. Low-temperature micro-SQUID measurements on oriented single
      crystals of 1 confirm the easy-axis type magnetic anisotropy suggested by
      conventional SQUID magnetometry. However magnetization hysteresis is not observed
      down to 0.04 K, which is ascribed to rapid quantum tunneling of the magnetization
      associated with transverse interactions.

PMID- 15847426
TI  - Influence of Pt nanocrystallinity on electrochromism of TiO2.
AB  - The Pt nanocrystals as nanonetwork conductors improved electrochromic properties
      of TiO2 such as increased optical modulation and fast response time, compared to
      pure TiO2 as well as TiO2 incorporated by amorphous Pt nanophases. It is likely
      that an enhancement of cathodic electrochromism in TiO2-Pt is due to an improved
      injection or extraction of electron/proton caused by Pt nanocrystals.

PMID- 15847427
TI  - Structural and magnetic diversity in tetraalkylammonium salts of anionic
      M[N(CN)2]3(-) (M = Mn and Ni) three-dimensional coordination polymers.
AB  - Tetraalkylammonium cations, (NR4)+ (R = C3H7, C4H9, and C5H11), have been used as
      templates to form a new family of [M(dca)3]- [M = Mn and Ni; dca = dicyanamide or
      N(CN)2(-)] salts. The tetrapropylammonium (TPrA) salts possess a perovskite-type
      anion structure. (TPrA)[Mn(dca)3] (1) crystallizes in the tetragonal space group
      P42(1)c, with a = 16.2945(8) A, c = 17.4321(8) A, and V = 4628.4(6) A(3) at T =
      298 K. At room temperature, (TPrA)[Ni(dca)3] (2) crystallizes in the orthorhombic
      space group Pnna, with a = 17.171(2) A, b = 22.992(2) A, c = 22.750(2) A, and V =
      8981(2) A3, but undergoes a first-order phase transition within the temperature
      range 150-220 K to the tetragonal space group P42(1)c, with a = 16.0985(7) A, c =
      17.0287(8) A, and V = 4413.2(5) A3 at T = 160 K. At 110 K, 2 returns to the Pnna
      space group with a = 17.116(2) A, b = 22.800(3) A, c = 22.641(3) A, and V =
      8835(3) A3. The tetrabutylammonium (TBA) salts possess a triple rutile structure.
      (TBA)[Mn(dca)3] (3) crystallizes in the orthorhombic space group P2(1)2(1)2, with
      a = 16.0107(6) A, b = 16.0114(6), c = 21.5577(8) A, and V = 5526.4(5) A3.
      (TBA)[Ni(dca)3] (4) also crystallizes in the orthorhombic space group P2(1)2(1)2,
      with a = 15.6842(5) A, b = 15.6841(6) A, c = 21.1551(8) A, and V = 5204.0(5) A3.
      The tetrapentylammonium (TPnA) salts crystallize with a LiSbO3 structure type,
      space group Pnna. Lattice parameters for (TPnA)[Mn(dca)3] (5) are a = 13.2236(6)
      A, b = 11.6300(6) A, c = 20.3176(9) A, and V = 3124.6(4) A3, and for
      (TPnA)[Ni(dca)3] (6), a = 12.9380(4) A, b = 11.6233(4) A, c = 19.8038(7) A, and V
      = 2978.1(2) A3. Long-range antiferromagnetic ordering has been observed in the
      manganese salts below 2.1 K, as indicated by alternating current susceptibility
      measurements. Magnetic susceptibility data for the nickel salts do not show
      evidence for long-range magnetic ordering but can be described using an S = 1
      zero-field splitting model with the exchange Hamiltonian H = -J sigma(S(i)S(i+1))
      + D sigma((S(i)z)2) + g mu(beta)B sigma(S(i)), giving absolute value(D)/kB values
      that range between 1.98(1) K and 3.20(2) K.

PMID- 15847428
TI  - Nanophase iron phosphate, iron arsenate, iron vanadate, and iron molybdate
      minerals synthesized within the protein cage of ferritin.
AB  - Nanoparticles of iron phosphate, iron arsenate, iron molybdate, and iron vanadate
      were synthesized within the 8 nm interior of ferritin. The synthesis involved
      reacting Fe(II) with ferritin in a buffered solution at pH 7.4 in the presence of
      phosphate, arsenate, vanadate, or molybdate. O2 was used as the oxidant to
      deposit the Fe(III) mineral inside ferritin. The rate of iron incorporation into
      ferritin was stimulated when oxo-anions were present. The simultaneous deposition
      of both iron and the oxo-anion was confirmed by elemental analysis and energy
      dispersive X-ray analysis. The ferritin samples containing iron and one of the
      oxo-anions possessed different UV/vis spectra depending on the anion used during
      mineral formation. TEM analysis showed mineral cores with approximately 8 nm
      mineral particles consistent with the formation of mineral phases inside
      ferritin.

PMID- 15847429
TI  - Sensitive oxidation state ambivalence in unsymmetrical three-center (M/Q/M)
      systems [(acac)2 Ru(mu-Q)Ru(acac)2](n), Q = 1,10-phenanthroline-5,6-dione or 1,10
      phenanthroline-5,6-diimine (n = +, 0, -, 2-).
AB  - The new redox systems [(acac)2 Ru(mu-Q1)Ru(acac)2](n) (1(n)) and [(acac)2 Ru(mu
      Q2)Ru(acac)2](n) (2(n)) with Q1 = 1,10-phenanthroline-5,6-dione and Q2 = 1,10
      phenanthroline-5,6-diimine were studied for n = +, 0, -, and 2- using UV-Vis-NIR
      spectroelectrochemistry and, in part, EPR and susceptometry. The ligands can bind
      the first metal (left) through the phenanthroline nitrogen atoms and the second
      metal (right) at the o-quinonoid chelate site. The neutral compounds are already
      different: Compound 1 is formulated as a Ru(II)(mu-Q1)*- Ru(III) species with
      partially coupled semiquinone and ruthenium(III) centers. In contrast, a
      Ru(III)(mu-Q2)2- Ru(III) structure is assigned to 2, which shows a weak
      antiferromagnetic spin-spin interaction (J = -1.14 cm(-1)) and displays an
      intense half-field signal in the EPR spectrum. The one-electron reduced forms are
      also differently formulated as Ru(II)(mu-Q1)2- Ru(III) for 1(-) with a Ru(III)
      typical EPR response and as Ru(II)(mu-Q2)*- Ru(II) for 2(-) with a radical-type
      EPR signal at g = 2.0020. In contrast, both 1(2-) and 2(2-) can only be described
      as Ru(II)(mu-Q)2- Ru(II) species. The monooxidized forms 1(+) and 2(+) show very
      similar spectroscopy, including a Ru(III)-type EPR signal. Although no
      unambiguous assignment was possible here for the alternatives Ru(II)(mu
      Q)0Ru(III), Ru(III)(mu-Q)2- Ru(IV) or Ru(III)(mu-Q)*- Ru(III), the last
      description is favored. The reasons for identical or different oxidation state
      combinations are discussed.

PMID- 15847430
TI  - A new strategy for the improvement of photophysical properties in ruthenium(II)
      polypyridyl complexes. Synthesis and photophysical and electrochemical
      characterization of six mononuclear ruthenium(II) bisterpyridine-type complexes.
AB  - The synthesis and characterization of six ruthenium(II) bistridentate polypyridyl
      complexes is described. These were designed on the basis of a new approach to
      increase the excited-state lifetime of ruthenium(II) bisterpyridine-type
      complexes. By the use of a bipyridylpyridyl methane ligand in place of
      terpyridine, the coordination environment of the metal ion becomes nearly
      octahedral and the rate of deactivation via ligand-field (i.e., metal-centered)
      states was reduced as shown by temperature-dependent emission lifetime studies.
      Still, the possibility to make quasi-linear donor-ruthenium-acceptor triads is
      maintained in the complexes. The most promising complex shows an excited-state
      lifetime of tau = 15 ns in alcohol solutions at room temperature, which should be
      compared to a lifetime of tau = 0.25 ns for [Ru(tpy)2]2+. The X-ray structure of
      the new complex indeed shows a more octahedral geometry than that of
      [Ru(tpy)2]2+. Most importantly, the high excited-state energy was retained, and
      thus, so was the potential high reactivity of the excited complex, which has not
      been the case with previously published strategies based on bistridentate
      complexes.

PMID- 15847431
TI  - Homodinuclear iron thiolate nitrosyl compounds [(ON)Fe(S,S-C6H4)2 Fe(NO)2]- and
      [(ON)Fe(SO2,S-C6H4)(S,S-C6H4)Fe(NO)2]- with {Fe(NO)}7-{Fe(NO)2}9 electronic
      coupling: new members of a class of dinitrosyl iron complexes.
AB  - Reaction of Fe(CO)2(NO)2 and [(ON)Fe(S,S-C6H3R)2]- (R = H (1), CH3 (1
      Me))/[(ON)Fe(SO2,S-C6H4)(S,S-C6H4)]- (4) in THF afforded the diiron
      thiolate/sulfinate nitrosyl complexes [(ON)Fe(S,S-C6H3R)2 Fe(NO)2]- (R = H (2),
      CH3 (2-Me)) and [(ON)Fe(S,SO2-C6H4)(S,S-C6H4)Fe(NO)2]- (3), respectively. The
      average N-O bond lengths ([Fe(NO)2] unit) of 1.167(3) and 1.162(4) A in complexes
      2 and 3 are consistent with the average N-O bond length of 1.165 A observed in
      the other structurally characterized dinitrosyl iron complexes with an {Fe(NO)2}9
      core. The lower nu(15NO) value (1682 cm(-1) (KBr)) of the [(15NO)FeS4] fragment
      of [(15NO)Fe(S,S-C6H3CH3)2 Fe(NO)2]- (2-Me-15N), compared to that of
      [(15NO)Fe(S,S-C6H3CH3)2]- (1-Me-15N) (1727 cm(-1) (KBr)), implicates the electron
      transfer from {Fe(NO)2}10 Fe(CO)2(NO)2 to complex 1-Me/1 may occur in the process
      of formation of complex 2-Me/2. Then, the electronic structures of the [(NO)FeS4]
      and [S2Fe(NO)2] cores of complexes 2, 2-Me, and 3 were best assigned according to
      the Feltham-Enemark notation as the {Fe(NO)}7-{Fe(NO)2}9 coupling
      (antiferromagnetic interaction with a J value of -182 cm(-1) for complex 2) to
      account for the absence of paramagnetism (SQUID) and the EPR signal. On the basis
      of Fe-N(O) and N-O bond distances, the dinitrosyliron {L2Fe(NO)2} derivatives
      having an Fe-N(O) distance of approximately 1.670 A and a N-O distance of
      approximately 1.165 A are best assigned as {Fe(NO)2}9 electronic structures,
      whereas the Fe-N(O) distance of approximately 1.650 A and N-O distance of
      approximately 1.190 A probably imply an {Fe(NO)2}10 electronic structure.

PMID- 15847432
TI  - Structural variability and dynamics in carboxylato- and carbamatomagnesium
      bromides. Relationship to the carboxylate shift.
AB  - Two new carbamatomagnesium bromide complexes 1 (=[Mg(O2CN(Me)Ph)(THF)2Br]2) and 2
      (=[Mg3(O2CNPh2)4(THF)5Br][(THF)MgBr3]) were prepared and crystallographically
      characterized. Complex 1 consists of a dinuclear core with two syn-syn-mu(1,3)
      bridging carbamato ligands. In solution, the 1H and 13C NMR spectra revealed a
      two-site fluxional behavior for the carbamato ligands between 0 degrees C and 25
      degrees C that is consistent with a bridge-mode isomerization relating the syn
      syn-mu(1,3) form and an alternative syn-anti-mu(1,1) form. At temperatures below
      0 degrees C, a more complex NMR signal is observed that is ascribed to further
      resolution of C-N rotational isomers, which has the effect of increasing the
      number of molecular isomers that can be resolved on the NMR time scale. New
      temperature-dependent NMR spectra of the previously known diethylcarbamato- and
      benzoato-bridged complexes [Mg(O2CNEt2)(THF)2Br]2, 3, and [Mg(O2CPh)(THF)2Br]2,
      5, revealed fluxional behavior that was also interpreted in terms of bridge-mode
      isomerization. Kinetic activation parameters for 1, 3, and 5 are consistent with
      an intramolecular motion relating the syn-syn-mu(1,3) and syn-anti-mu(1,1)
      isomers. These results provide new insight into bridge-mode isomerism that is
      closely related to the carboxylate shift concept. Complex 2 is compositionally
      related to 1 but exists as a salt consisting of a trinuclear cationic unit
      [Mg3(O2CNPh2)4(THF)5Br]+ and a solvated tribromomagnesiate anion [(THF)MgBr3]-.
      This shows that changing the hydrocarbon substituents on the carbamato ligand
      changes the structure and dynamics of multinuclear carbamatomagnesium complexes
      in ways that limit our ability to predict structural topologies in this system.

PMID- 15847433
TI  - New members of an old family: isolation of IC(O)Cl and IC(O)Br and evidence for
      the formation of weakly bound Br*...CO.
AB  - The photochemically induced reactions of a dihalogen, XY, with CO isolated
      together in an Ar matrix at about 15 K lead to the formation of carbonyl dihalide
      molecules XC(O)Y, where X and Y may be the same or different halogen atoms, Cl,
      Br, or I. In addition to the known compounds OCCl2, OCBr2, and BrC(O)Cl, the
      carbonyl iodide chloride, IC(O)Cl, and carbonyl iodide bromide, IC(O)Br,
      compounds have thus been identified for the first time as products of the
      reactions involving ICl and IBr, respectively. The first product to be formed in
      reactions with Cl2, BrCl, or ICl is the ClCO* radical, which reacts subsequently
      with a second halogen atom to give the corresponding carbonyl dihalide [OCCl2,
      BrC(O)Cl, or IC(O)Cl]. The analogous reaction with Br2 affords, in low yield, the
      unusually weakly bound BrCO* radical, better described as a van der Waals
      complex, Br*...CO. The changes have been followed and the products characterized
      experimentally by their infrared spectra, and the spectra have been analyzed in
      light of the results afforded by ab initio (Hartree-Fock and Moeller-Plesset
      second-order) and density functional theory calculations.

PMID- 15847434
TI  - Coordination behavior toward copper(II) and zinc(II) ions of three ligands
      joining 3-hydroxy-2-pyridinone and polyaza fragments.
AB  - The synthesis and characterization of new polydentate ligand 2-(N),2'-(N')-bis[2
      (3-hydroxy-2-oxo-2H-pyridin-1-yl)acetamido]-1(N'),2(N),2'(N')-trimethyl-2,2'
      diaminodiethylamine (L3) is reported. The coordination properties of L3 and of
      two analogous macrocyclic ligands (L1 and L2) toward Cu(II) and Zn(II) metal ions
      are reported. All three ligands show the 3-hydroxy-2(1H)-pyridinone (HPO) groups
      attached as sidearms to a polyaza fragment, which is a macrocyclic framework in
      the case of L1 and L2 while it is an open chain in the case of L3. The role of
      the polyaza fragments in preorganizing the two sidearms was investigated. The
      basicity of L3 and the binding properties of L1-L3 were determined by means of
      potentiometric measurements in aqueous solution (298.1 +/- 0.1 K, I = 0.15 mol
      dm(-3)). UV-vis spectra as well 1H and 13C NMR experiments were used to
      understand the role of the HPO and of the polyaza fragments in the stabilization
      of the cations. While L1 forms stable mono- and dinuclear complexes, L2 and L3
      can form only mononuclear species with each of the metal ions investigated. In
      the main mononuclear species of L2 and L3, the two HPO moieties stabilize the
      M(II) in a square planar geometry due to the two oxygen atoms of each HPO. The
      coordination sphere of the metal is completed by adding a secondary ligand such
      as water molecules in the case of Cu(II) systems or OH- in the Zn(II) systems.
      These results are confirmed by the crystal structures of the [CuH(-1)L2]+ and
      [CuH(-1)L3]+ species reported herein. Two conformations of L1 can be hypothesized
      in the formation of the dinuclear species, as suggested by NMR experiments on the
      [ZnH(-2)L1] species, which shows two conformers slowly interchanging on the NMR
      time scale, one of which was found to be more insoluble.

PMID- 15847435
TI  - Mixed-metal cluster chemistry. 28. Core enlargement of tungsten-iridium clusters
      with alkynyl, ethyndiyl, and butadiyndiyl reagents.
AB  - Reaction of [WIr3(mu-CO)3(CO)8(eta-C5Me5)] (1c) with [W(C[triple
      bond]CPh)(CO)3(eta-C5H5)] afforded the edge-bridged tetrahedral cluster
      [W2Ir3(mu4-eta2-C2Ph)(mu-CO)(CO)9(eta-C5H5)(eta-C5Me5)] (3) and the edge-bridged
      trigonal-bipyramidal cluster [W3Ir3(mu4-eta2-C2Ph)(mu-eta2-C=CHPh)(Cl)(CO)8(eta
      C5Me5)(eta-C5H5)2] (4) in poor to fair yield. Cluster 3 forms by insertion of
      [W(C[triple bond]CPh)(CO)3(eta-C5H5)] into Ir-Ir and W-Ir bonds, accompanied by a
      change in coordination mode from a terminally bonded alkynyl to a mu4-eta2
      alkynyl ligand. Cluster 4 contains an alkynyl ligand interacting with two iridium
      atoms and two tungsten atoms in a mu4-eta2 fashion, as well as a vinylidene
      ligand bridging a W-W bond. Reaction of [WIr3(CO)11(eta-C5H5)] (1a) or 1c with
      [(eta-C5H5)(CO)2 Ru(C[triple bond]C)Ru(CO)2(eta-C5H5)] afforded [Ru2WIr3(mu5-eta2
      C2)(mu-CO)3(CO)7(eta-C5H5)2(eta-C5R5)] [R = H (5a), Me (5c)] in low yield, a
      structural study of 5a revealing a WIr3 butterfly core capped and spiked by Ru
      atoms; the diruthenium ethyndiyl precursor has undergone Ru-C scission, with
      insertion of the C2 unit into a W-Ir bond of the cluster precursor. Reaction of
      [W2Ir2(CO)10(eta-C5H5)2] with the diruthenium ethyndiyl reagent gave [RuW2Ir2{mu4
      eta2-(C2C[triple bond]C)Ru(CO)2(eta-C5H5)}(mu-CO)2(CO)6(eta-C5H5)3] (6) in low
      yield, a structural study of 6 revealing a butterfly W2Ir2 unit capped by a
      Ru(eta-C5H5) group resulting from Ru-C scission; the terminal C2 of a new
      ruthenium-bound butadiyndiyl ligand has been inserted into the W-Ir bond.
      Reaction between 1a, [WIr3(CO)11(eta-C5H4Me)] (1b), or 1c and [(eta
      C5H5)(CO)3W(C[triple bond]CC[triple bond]C)W(CO)3(eta-C5H5)] afforded [W2Ir3{mu4
      eta2-(C2C[triple bond]C)W(CO)3(eta-C5H5)}(mu-CO)2(CO)2(eta-C5H5)(eta-C5R5)] [R =
      H (7a), Me (7c); R5 = H4Me (7b)] in good yield, a structural study of 7c
      revealing it to be a metallaethynyl analogue of 3.

PMID- 15847436
TI  - Synthesis, structures, and magnetic properties of tri- and dinuclear copper(II)
      gadolinium(III) complexes of linear oligooxime ligands.
AB  - We have designed and synthesized a new Cu2Gd heterotrinuclear complex,
      [LCu2Gd(OAc)3] (1), where H4L is a bis(salen)-type tetraoxime ligand useful in
      the synthesis of discrete (3d)2(4f) complexes. Complex 1 crystallizes in the
      triclinic system, space group P1, with unit cell parameters a = 12.442(4) A, b =
      13.397(3) A, c = 13.966(4) A, alpha = 77.052(8) degrees, beta = 88.656(10)
      degrees, gamma = 77.761(8) degrees, and Z = 2. In the crystal structure of 1, Cu
      Gd distances are 3.3-3.5 A, whereas the two Cu atoms are separated by 6.08 A. The
      corresponding dinuclear CuGd complexes, 2 and 3, with mono(salen)-type chelate 3
      MeOsalamo were also synthesized. Complex 2 crystallizes in the monoclinic system,
      space group P2(1)/c, with unit cell parameters a = 13.869(8) A, b = 13.688(7) A,
      c = 18.728(10) A, beta = 92.861(8) degrees, and Z = 4, and complex 3 crystallizes
      in the triclinic system, space group P1, with unit cell parameters a = 12.319(4)
      A, b = 13.989(4) A, c = 16.774(5) A, alpha = 64.699(14) degrees, beta =
      66.672(13) degrees, gamma = 76.891(17) degrees, and Z = 4. Interaction between
      Cu(II) and Gd(III) in the dinuclear complexes 2 and 3 is ferromagnetic (J = 4.5
      and 7.6 cm(-1), respectively, using spin Hamiltonian H = -JS(Cu) x S(Gd)) as
      observed in the previously prepared [LCuGdX3] complexes, where L is a salen-type
      chelate. Magnetic data for the Cu2Gd trinuclear complex can be reasonably
      interpreted with the use of a spin Hamiltonian H = -J(CuGd)S(Cu1) x S(Gd) -
      J(CuGd)S(Cu2) x S(Gd) - J(CuCu)S(Cu1) x S(Cu2) with J(CuGd) = 5.0 cm(-1) and
      J(CuCu) = 0 cm(-1). The S = 9/2 ground state resulted from the ferromagnetic
      interaction among the Cu(II)-Gd(III)-Cu(II) triad was also supported by the
      saturation magnetization at 1.8 K.

PMID- 15847437
TI  - Auration, argentation, and mercuration reactions of an iridaphosphirene.
AB  - The reactions of the iridaphosphirene complex [Ir{=C(tBu)P(Cy)}(CO)(PPh3)2] (Cy =
      cyclohexyl) with either [AuCl(tht)] (tht = tetrahydrothiophene) or AgCl result in
      the products [Ir{=C(tBu)P[M(Cl)](Cy)}(CO)(PPh3)2], M = Au or Ag. The aurated
      product can additionally be obtained on reaction of the iridaphosphirene with
      [AuCl(CNtBu)], via loss of the isocyanide ligand. Treatment of
      [Ir{=C(tBu)P(Cy)}(CO)(PPh3)2] with [AuCl(PPh3)] in the presence of silver
      triflate leads to the isolation of the salt,
      [Ir{=C(tBu)P[Au(PPh3)](Cy)}(CO)(PPh3)2][SO3CF3]. Reaction of the iridaphosphirene
      with PhHgCl in the absence or presence of silver triflate affords the mercurated
      species [Ir{=C(tBu)P[Hg(Ph)](Cy)}(CO)(PPh3)2]X, X = Cl or CF3SO3, respectively.
      The former exhibits a weakly mercury-coordinated chloride ion. The X-ray crystal
      structures of all of the complexes are described.

PMID- 15847438
TI  - Characterization of the low-energy electronic excited states of benzoyl
      substituted ruthenocenes.
AB  - Electronic absorption and resonance Raman spectral studies of benzoylruthenocene
      (BRc) and 1,1'-dibenzoylruthenocene (DRc) indicate that the low-energy electronic
      excited states of these 4d(6) metallocenes possess metal-to-ligand charge
      transfer (MLCT) character. While this MLCT contribution should weaken the metal
      ring bonding in the excited state, neither compound is photosensitive in
      nonhalogenated solvents such as methanol, acetonitrile, and cyclohexane. In
      contrast, irradiating BRc and DRc in the good electron-accepting solvent, carbon
      tetrachloride, results in ring loss via a pathway that appears to originate from
      a charge-transfer-to-solvent excited state. Both metallocenes function as
      photoinitiators for the anionic polymerization of ethyl 2-cyanoacrylate, and the
      kinetics and mechanism of this process have been investigated. Comparing the
      present results on BRc and DRc with those reported earlier for the corresponding
      benzoyl-substituted ferrocene compounds reveals some interesting commonalities
      and differences between the excited-state properties of these 3d and 4d
      metallocenes.

PMID- 15847439
TI  - Platinum(II) and palladium(II) complexes of bisphosphine ligands bearing o-N,N
      dimethylanilinyl substituents: a hint of catalytic olefin hydration.
AB  - Platinum(II) and palladium(II) complexes of the potentially hexadentate P,N-donor
      ligand family Ar2P-X-PAr2 (X = (CH2)2 [dmape], cyclic-C5H8 [dmapcp]; Ar = o-N,N
      dimethylanilinyl) are described. In CH2Cl2, the dmape complexes exist as
      equilibrium mixtures of MCl2(P,P'-dmape) and [MCl(P,P',N-dmape)]Cl isomers (M =
      Pd, Pt), governed by deltaH(o) = -19 +/- 4 kJ mol(-1) and deltaS(o) = -100 +/- 30
      J mol(-1) K(-1) for M = Pt, and deltaH(o) = -11 +/- 7 kJ mol(-1) and deltaS(o) = 
      60 +/- 20 J mol(-1) K(-1) for M = Pd. The water-soluble dmapcp complexes exist
      solely in the [MCl(P,P',N-dmapcp)]Cl form, but the free and coordinated anilinyl
      rings in these complexes are in slow diastereoselective exchange. X-ray crystal
      structures for MCl2(P,P'-dmape) (M = Pd, Pt), and the [PdCl(P,P',N-dmape)]+ and
      [PtCl(P,P',N-dmapcp)]+ cations, are presented. Some of the complexes show
      marginal activity in water for the catalyzed hydration of maleic to malic acid,
      giving about 6-7% conversion in 24 h at 100 degrees C and substrate:catalyst
      loadings of 100:1. Attempts to synthesize a PdCl(P,P',N-dmapm)+ species led
      instead to isolation of [Pd(mu-Cl)(P,P'-dmapm)]2[PF6]2 (dmapm = Ar2PCH2Ar2).

PMID- 15847440
TI  - Sparkle model for the calculation of lanthanide complexes: AM1 parameters for
      Eu(III), Gd(III), and Tb(III).
AB  - Our previously defined Sparkle model (Inorg. Chem. 2004, 43, 2346) has been
      reparameterized for Eu(III) as well as newly parameterized for Gd(III) and
      Tb(III). The parameterizations have been carried out in a much more extensive
      manner, aimed at producing a new, more accurate model called Sparkle/AM1, mainly
      for the vast majority of all Eu(III), Gd(III), and Tb(III) complexes, which
      possess oxygen or nitrogen as coordinating atoms. All such complexes, which
      comprise 80% of all geometries present in the Cambridge Structural Database for
      each of the three ions, were classified into seven groups. These were regarded as
      a "basis" of chemical ambiance around a lanthanide, which could span the various
      types of ligand environments the lanthanide ion could be subjected to in any
      arbitrary complex where the lanthanide ion is coordinated to nitrogen or oxygen
      atoms. From these seven groups, 15 complexes were selected, which were defined as
      the parameterization set and then were used with a numerical multidimensional
      nonlinear optimization to find the best parameter set for reproducing chemical
      properties. The new parameterizations yielded an unsigned mean error for all
      interatomic distances between the Eu(III) ion and the ligand atoms of the first
      sphere of coordination (for the 96 complexes considered in the present paper) of
      0.09 A, an improvement over the value of 0.28 A for the previous model and the
      value of 0.68 A for the first model (Chem. Phys. Lett. 1994, 227, 349). Similar
      accuracies have been achieved for Gd(III) (0.07 A, 70 complexes) and Tb(III)
      (0.07 A, 42 complexes). Qualitative improvements have been obtained as well;
      nitrates now coordinate correctly as bidentate ligands. The results, therefore,
      indicate that Eu(III), Gd(III), and Tb(III) Sparkle/AM1 calculations possess
      geometry prediction accuracies for lanthanide complexes with oxygen or nitrogen
      atoms in the coordination polyhedron that are competitive with present day ab
      initio/effective core potential calculations, while being hundreds of times
      faster.

PMID- 15847441
TI  - Copper-zinc superoxide dismutase: theoretical insights into the catalytic
      mechanism.
AB  - The mechanism for the toxic superoxide radical disproportionation to molecular
      oxygen and hydrogen peroxide by copper-zinc superoxide dismutase (CuZnSOD) has
      been studied using the B3LYP hybrid density functional. On the basis of the X-ray
      structure of the enzyme, the molecular system investigated includes the first
      shell protein ligands of the two metal centers as well as the second-shell ligand
      Asp122. The substrates of the model reaction are two superoxide radical anions,
      approaching the copper center at the beginning of two half-reactions: the first
      part of the catalytic cycle involving Cu+ oxidation and the second part reducing
      Cu2+ back to its initial state. The quantitative free energy profile of the
      reaction is obtained and discussed in connection with the experimental data on
      the reduction potentials and CuZnSOD kinetics. The optimized structures are
      analyzed and compared to the experimental ones. The two transition states
      alternate the protonation state of His61 and correspond to histidine Cu-His61-Zn
      bridge rupture/reformation. Modifications applied to the initial model allow the
      importance of Asp122 for catalysis to be estimated.

PMID- 15847442
TI  - Zinc complex chemistry of N,N,O ligands providing a hydrophobic cavity.
AB  - Three new highly substituted bis(2-picolyl)(2-hydroxybenzyl)amine ligands were
      synthesized, and their biomimetic zinc complex chemistry was explored. They have
      tert-butyl substituents at the 3-and 5-positions of their phenyl rings, and they
      bear one phenyl group (HL2), two methyl groups (HL3), or two phenyl groups (HL4)
      at the 6-positions of their pyridyl rings. Their reactions with hydrated zinc
      perchlorate yield three distinctively different complex types. L2 forms a
      trigonal-bipyramidal aqua complex, and L3, a square-pyramidal aqua complex. The
      substituents on L4 leave no room for a water ligand, and the resulting zinc
      complex is trigonal-monopyramidal with a vacant coordination site. The water
      ligands on the L2Zn and L3Zn units can be replaced by anionic halide,
      thiocyanate, p-nitrophenolate, benzoate, and organophosphate as well as uncharged
      pyridine ligands. The L4Zn unit forms labile halide, p-nitrophenolate, and
      pyridine complexes. Triethylamine converts the aqua complexes to the labile
      hydroxides L2Zn-OH and L3Zn-OH, and in polar media [L3Zn-OH2]+ seems to be in
      equilibrium with L3Zn-OH. The hydroxides, but not the water complexes, effect the
      hydrolytic cleavage of tris(p-nitrophenyl) phosphate to bis(p-nitrophenyl)
      phosphate. The kinetic investigation of the cleavage reactions has shown them to
      be second-order reactions, thereby supporting the proposed four-center mechanism.

PMID- 15847443
TI  - Syntheses, crystal structures, and magnetic properties of novel manganese(II)
      complexes with flexible tripodal ligand 1,3,5-tris(imidazol-1-ylmethyl)-2,4,6
      trimethylbenzene.
AB  - Two novel metal-organic frameworks (MOFs)--[Mn(titmb)(N3)2] x 1.5H2O (1) and
      [Mn3(titmb)2(C2O4)3(H2O)] x 10H2O (2)--were obtained by reactions of the flexible
      tripodal ligand 1,3,5-tris(imidazol-1-ylmethyl)-2,4,6-trimethylbenzene (titmb)
      with Mn(OAc)2 x 4H2O, together with NaN3 and K2C2O4, respectively. The structures
      of these MOFs were established by single-crystal X-ray diffraction analysis. The
      crystal data for 1 were as follows: monoclinic, C2/c, a = 20.956(13) A, b =
      9.884(6) A, c = 24.318(14) A, beta = 95.87(5) degrees, Z = 8. The crystal data
      for 2 were as follows: triclinic, P1, a = 12.400(9) A, b = 16.827(12) A, c =
      17.196(11) A, alpha = 66.35(5), beta = 95.87(5) degrees, gamma = 71.03(6), Z = 2.
      Complex 1 is a novel noninterpenetrating three-dimensional (3D) framework, in
      which the azide ligand connects Mn(II) atoms in an end-to-end (EE) mode to give
      [Mn-N-N-N-]n infinite one-dimensional (1D) chains, and complex 2 has a two
      dimensional (2D) network structure in which the Mn(II) ions are linked by the
      oxalate anions to form 1D [Mn(C2O4)]n chains. Each titmb in these two complexes
      connects three metal atoms and serves as a three-connecting ligand. The magnetic
      properties of 1 and 2 were investigated. The results showed that the
      antiferromagnetic interactions occurred between the Mn(II) ions linked by the
      azide ligands in complex 1, and those linked by the oxalate anions and the
      carboxylate in syn-anti coordination mode in complex 2. The entirely different
      structures of complexes 1 and 2, on one hand, indicate that the azide and the
      oxalate ligands affected the structures of MOFs greatly, and on the other hand,
      reveals the potential applications of MOFs with the azide and oxalate ligands,
      which are efficient magnetic couplers.

PMID- 15847444
TI  - Synthesis, structural characterization, and magnetic studies of polynuclear iron
      complexes with a new disubstituted pyridine ligand.
AB  - A series of novel polyiron species have been prepared from the reaction of iron
      chloride with the 2,5-disubstituted pyridines H2L(n) (H2L1) = N,N'-bis(n
      butylcarbamoyl)pyridine-2,6-dicarboxamide; H2L2 = N,N'-bis(n
      ethylcarbamoyl)pyridine-2,6-dicarboxamide). By small modifications of the
      experimental conditions under which the reactions are carried out, it has been
      possible to prepare the quadruply stranded diiron(II) complex [Fe2(mu-H2L1)4(mu
      Cl)2][FeCl4]2 (1), the metallamacrocycle [Fe2(mu-H2L1)2(THF)4Cl2][FeCl4]2 (2),
      the hexairon(III) compound [Fe6(L1)2(mu-OMe)6(mu4-O)2Cl4] (3), and the mixed
      valence trinuclear iron complexes [Fe3(L(n))3(mu3-O)] (n = 1, 4; n = 2, 5). The X
      ray crystal structures of 3 and 5 and magnetic studies for all the compounds are
      herein presented. Interestingly, the structural analysis of 5 at room temperature
      indicates that one of the iron centers is Fe(III) while the other two have an
      average valence state between Fe(II) and Fe(III). The five complexes herein
      presented demonstrate the great versatility that the new ligand has as a building
      block for the formation of supramolecular coordination assemblies.

PMID- 15847445
TI  - Redox-active dithiafulvenyldiphenylphosphine as a mono- or bidentate ligand:
      intramolecular coupling reaction in the coordination sphere of a metal carbonyl
      fragment.
AB  - The coordinating ability of dithiafulvenyldiphenylphosphine (P-DTF) has been
      investigated with cis-W(CO)4(piperi-dine)2. As shown by the metal carbonyl
      complexes obtained, this redox-active vinylphosphine can act as a monodentate (P)
      and as a bidentate (P,S) ligand. Oxidation of cis-M(CO)4(P-DTF)2, M = Mo and W,
      leads to the carbon-carbon bond formation between the two coordinated
      dithiafulvenyldiphenylphosphines. This chemical coupling of the dithiafulvenyl
      cores in the coordination sphere of M(CO)4 (M = Mo, W) fragment has been studied
      in the presence of various oxidizing agents. The use of (BrC6H4)3NSbCl6 or AgBF4
      induces the formation of a five-membered metallacycle with a vinylogous TTF
      backbone while DDQ leads to a six-membered metallacycle. The syntheses, crystal
      structures, and electrochemical properties of the complexes obtained are
      described.

PMID- 15847446
TI  - Gas-phase reactivity of heterobinuclear oxometalate anions [CrMoO6(OR)]-,
      [CrWO6(OR)]-, and [MoWO6(OR)]- (R = H, nBu).
AB  - Heterobinuclear oxometalate anions based upon [CrMoO7]2-, [CrWO7]2-, and [MoWO7]2
      were generated and transferred to the gas phase by the electrospray process from
      acetonitrile solutions containing two of the salts (Bu4N)2[MO4] (M = Cr, Mo, W).
      Their reactivities were examined and compared with those of the related
      homobinuclear anions based upon [M2O7]2- (M = Cr, Mo, W). Particular emphasis was
      placed upon reactions relevant to gas-phase catalytic cycles described previously
      for oxidation of alcohols by [Mo2O6(OH)]- (Waters, T.; O'Hair, R. A. J.; Wedd, A.
      G. J. Am. Chem. Soc. 2003, 125, 3384-3396). The protonated anions [MM'O6(OH)]-
      each reacted with methanol with loss of water to form [MM'O6(OCH3)]- at a rate
      that was intermediate between those of [M2O6(OH)]- and [M'2O6(OH)]-. The
      butylated anions [MM'O6(OBu)]- were generated by collisional activation of the
      ion-pairs {Bu4N+ [MM'O7]2-}-. Collisional activation of [MM'O6(OBu)]- resulted in
      either the loss of butanal (redox reaction) or the loss of butene (elimination
      reaction), with the detailed nature of the observations depending on the nature
      of both M and M'. Selective 18O labeling indicated that the butoxo ligands of
      [CrMoO6(OBu)]- and [CrWO6(OBu)]- were located on molybdenum and tungsten,
      respectively. This structural insight allowed a more detailed comparison of
      reactivity with the homobinuclear species, and highlighted the importance of the
      neighboring metal center in these reactions.

PMID- 15847447
TI  - Observation of bound-free transitions of the linear Ar...I2(X,v"=0) complex in
      and above the I2 B-X spectral region.
AB  - Laser-induced fluorescence and action spectroscopy experiments were performed to
      identify the origin of the Ar...I(2) continuum signals observed in and above the
      I(2) B-X spectral region. We have verified that these signals arise from
      transitions of the linear Ar...I(2) (X,v"=0) complex. The data provides no
      evidence that the excited state complexes undergo a one-atom caging mechanism
      when prepared above the I(2)(B) dissociation limit, Ar...I(2) (B)*-->Ar+I+I*-
      >Ar+I(2)(B,v'). Instead, our results indicate that the continuum signals result
      from bound-free transitions of the linear Ar...I(2) X,v(")=0) complex to the
      inner repulsive walls of numerous Ar+I(2)(B,v') intermolecular potentials. The
      bound-free continuum signal associated with transitions to each Ar+I(2)(B,v')
      potential spans an energy region >700 cm(-1). We have found that the continuum
      signals turn-on 250(2)cm(-1) above the corresponding I(2) B-X,v'-0 band origin,
      and this energy represents the binding energy of the linear Ar...I(2) (X,v"=0)
      conformer, D(0) (")(L)=250(2)cm(-1).

PMID- 15847448
TI  - Mode correlation of product pairs in the reaction OH+CD4-->HOD+CD3.
AB  - The hydrogen abstraction reaction from methane by a hydroxyl radical produces two
      polyatomic molecules. Each product has several vibrational modes that
      characterize distinct, concerted motions of the constituent atoms of the
      molecule. This communication describes the first measurement that maps out the
      coincident information on how the mode of excitation of one product varies with
      that of the other co-product. Such information on mode correlation of product
      pairs is particularly appealing in that it provides intuitively a glimpse of the
      reaction paths by which the chemical transformation occurs.

PMID- 15847449
TI  - How to choose one-dimensional basis functions so that a very efficient
      multidimensional basis may be extracted from a direct product of the one
      dimensional functions: energy levels of coupled systems with as many as 16
      coordinates.
AB  - In this paper we propose a scheme for choosing basis functions for quantum
      dynamics calculations. Direct product bases are frequently used. The number of
      direct product functions required to converge a spectrum, compute a rate
      constant, etc., is so large that direct product calculations are impossible for
      molecules or reacting systems with more than four atoms. It is common to extract
      a smaller working basis from a huge direct product basis by removing some of the
      product functions. We advocate a build and prune strategy of this type. The one
      dimensional (1D) functions from which we build the direct product basis are
      chosen to satisfy two conditions: (1) they nearly diagonalize the full
      Hamiltonian matrix; (2) they minimize off-diagonal matrix elements that couple
      basis functions with diagonal elements close to those of the energy levels we
      wish to compute. By imposing these conditions we increase the number of product
      functions that can be removed from the multidimensional basis without degrading
      the accuracy of computed energy levels. Two basic types of 1D basis functions are
      in common use: eigenfunctions of 1D Hamiltonians and discrete variable
      representation (DVR) functions. Both have advantages and disadvantages. The 1D
      functions we propose are intermediate between the 1D eigenfunction functions and
      the DVR functions. If the coupling is very weak, they are very nearly 1D
      eigenfunction functions. As the strength of the coupling is increased they
      resemble more closely DVR functions. We assess the usefulness of our basis by
      applying it to model 6D, 8D, and 16D Hamiltonians with various coupling
      strengths. We find approximately linear scaling.

PMID- 15847450
TI  - Linear scaling computation of the Fock matrix. VII. Periodic density functional
      theory at the Gamma point.
AB  - Linear scaling quantum chemical methods for density functional theory are
      extended to the condensed phase at the Gamma point. For the two-electron Coulomb
      matrix, this is achieved with a tree-code algorithm for fast Coulomb summation
      [M. Challacombe and E. Schwegler, J. Chem. Phys. 106, 5526 (1997)], together with
      multipole representation of the crystal field [M. Challacombe, C. White, and M.
      Head-Gordon, J. Chem. Phys. 107, 10131 (1997)]. A periodic version of the
      hierarchical cubature algorithm [M. Challacombe, J. Chem. Phys. 113, 10037
      (2000)], which builds a telescoping adaptive grid for numerical integration of
      the exchange-correlation matrix, is shown to be efficient when the problem is
      posed as integration over the unit cell. Commonalities between the Coulomb and
      exchange-correlation algorithms are discussed, with an emphasis on achieving
      linear scaling through the use of modern data structures. With these
      developments, convergence of the Gamma-point supercell approximation to the k
      space integration limit is demonstrated for MgO and NaCl. Linear scaling
      construction of the Fockian and control of error is demonstrated for RBLYP6-21G*
      diamond up to 512 atoms.

PMID- 15847451
TI  - Vibronic energies and spectra of molecular dimers.
AB  - We consider three distinct methods of calculating the vibronic levels and
      absorption spectra of molecular dimers coupled by dipole-dipole interactions. The
      first method is direct diagonalization of the vibronic Hamiltonian in a basis of
      monomer eigenstates. The second method is to use creation and annihilation
      operators leading in harmonic approximation to the Jaynes-Cummings Hamiltonian.
      The adiabatic approximation to this problem provides insight into spectral
      behavior in the weak and strong coupling limits. The third method, which serves
      as a check on the accuracy of the previous methods, is a numerically exact
      solution of the time-dependent Schrodinger equation. Using these methods, dimer
      spectra are calculated for three separate dye molecules and show good agreement
      with measured spectra.

PMID- 15847452
TI  - Charge transfer driven by electron correlation: a non-Dyson propagator approach.
AB  - A hole charge created in a molecular system, for instance, by ionization, can
      migrate through the system solely driven by electron correlation. This charge
      transfer due to electron correlation is referred to as charge migration. We
      introduce in this work a new ab initio method analyzing charge migration due to
      electron correlation in molecules. This method, a third-order "non-Dyson"
      propagator approach, aims in the long run, in particular, at the calculation of
      charge migration in relatively large molecules such as oligopeptides. First
      results of the new non-Dyson method are compared with a previously used
      propagator approach.

PMID- 15847453
TI  - Comparison of low-order multireference many-body perturbation theories.
AB  - Tests have been made to benchmark and assess the relative accuracies of low-order
      multireference perturbation theories as compared to coupled cluster (CC) and full
      configuration interaction (FCI) methods. Test calculations include the ground and
      some excited states of the Be, H(2), BeH(2), CH(2), and SiH(2) systems.
      Comparisons with FCI and CC calculations show that in most cases the effective
      valence shell Hamiltonian (H(v)) method is more accurate than other low-order
      multireference perturbation theories, although none of the perturbative methods
      is as accurate as the CC approximations. We also briefly discuss some of the
      basic differences among the multireference perturbation theories considered in
      this work.

PMID- 15847454
TI  - Truncation of the correlation consistent basis sets: extension to third-row (Ga
      Kr) molecules.
AB  - The systematic reduction of the commonly used correlation consistent basis sets
      [cc-pVnZ where n=D(2), T(3), Q(4), and 5] as a means to reduce computational cost
      has been extended to hydrogen-containing third-row (Ga-Kr) molecules of the G2
      test suite. Coupled cluster with singles, doubles, and quasiperturbative triple
      excitations [CCSD(T)] calculations were performed using both the full correlation
      consistent basis sets and a series of truncated basis sets in order to assess the
      impact of basis set reduction upon the structures and energies of the species.
      The impact that truncation of the basis sets for hydrogen has upon extrapolation
      of energies to the complete basis set limit also has been examined, and the cost
      savings that can be achieved are discussed. Overall, basis set reduction can be
      accomplished which preserves the systematic convergence behavior of the full
      correlation consistent basis sets.

PMID- 15847455
TI  - Generalized density functional theory for degenerate states.
AB  - An extension of density functional theory is proposed for degenerate states.
      There are suitably selected basic variables beyond the subspace density.
      Generalized Kohn-Sham equations are derived. A direct method is proposed to
      ensure the fixed value of ensemble quantities. Then the Kohn-Sham equations are
      similar to the conventional Kohn-Sham equations. But the Kohn-Sham potential is
      different for different ensembles. A simple local expression is proposed for the
      correlation energy.

PMID- 15847456
TI  - Relations between coordinate and potential scaling in the high-density limit.
AB  - Exact relations are derived between scaling to the high-density limit of density
      functional theory and taking Z to infinity for nondegenerate atoms. Gorling-Levy
      perturbation results are deduced for hydrogenic densities. The kinetic
      contribution to the correlation energy is also studied, and estimates given for
      its value for neutral atoms. Popular approximate functionals are tested against
      these benchmarks.

PMID- 15847457
TI  - Assigning signs to the electronic nonadiabatic coupling terms: the H2,O system as
      a case study.
AB  - This paper is devoted to a specific difficulty related to the electronic
      nonadiabatic coupling terms (NACT), namely, how to determine correctly their
      signs. It is well known that correct NACTs, including their signs, are crucial
      for any numerical treatment of the nuclear Schrodinger equation [see, i.e., A.
      Kuppermaan and R. Abrol, Adv. Chem. Phys. 124, 283 (2003)]. In most cases the
      derivation of the correct sign of the nonadiabatic coupling matrix (NACM) is done
      employing various continuity procedures. However, there are cases where these
      procedures do not suffice and for these cases we suggest to apply an additional
      procedure based on a mathematical lemma which asserts that the exponentiated line
      integral which yields the D matrix is invariant with respect to the initial point
      of the integration [M. Baer, J. Phys. Chem. A 104, 3181 (2000)]. In the numerical
      study we apply this lemma to determine the signs of the 3x3 NACM elements for the
      three excited states of the {H(2),O} system (some of these NACTs are presented
      here for the first time). It turns out that the ab initio treatment yields
      results from which one can form eight different 3x3 NACMs. However the
      application of this lemma (which does not require any significant additional
      numerical effort) reduces this number to two. The final selection is done by an
      enhanced numerical study which requires more accurate calculations.

PMID- 15847458
TI  - Using non-Gaussian density functional fits to improve relative free energy
      calculations.
AB  - The accurate and reliable computation of relative free energy differences remains
      an important long-term goal. Major stumbling blocks for achieving this goal
      reflect the difficulty of sampling in a known fashion along the reaction
      coordinate and of maximally combining information that has been collected from
      the simulation along the reaction coordinate. In this paper we examine the
      utility of a probability density functional type fit to the distribution of work
      events collected during a nonequilibrium sample along the reaction coordinate.
      This approach can readily be generalized to equilibrium sampling and has the
      potential to estimate the quality of a relative free energy estimate as data are
      being collected. The method may have the greatest utility for nonequilibrium
      sampling where non-Gaussian work distributions are generally present that are
      strongly dominated by rare event sampling in the tail region. We believe that the
      approach can be used to augment the design and the error analysis of relative
      free energy computations thus improving the ability to reliably and with known
      accuracy compute a relative free energy.

PMID- 15847459
TI  - Ionization potentials of large sodium doped ammonia clusters.
AB  - In a continuous neat supersonic expansion ammonia clusters are generated and
      doped with sodium atoms in a pickup cell. Thus clusters of the form Na(NH(3))(n)
      are produced that are photoionized by a tunable dye laser system. The ions are
      mass analyzed in a reflectron time-of-flight mass spectrometer, and the
      wavelength dependent ion signals serve for the determination of the ionization
      potentials (IP) of the different clusters in the size range 10< or =n< or =1500.
      Aside from a plateau for 10< or =n< or =17 and smaller steps at n=24, 35, and 59
      on the average a continuous decrease of the IP with cluster size is observed. The
      IPs in this size range are linear with (n+1)(-13) and extrapolate to
      IP(n=infinity)=1.66+/-0.01 eV. The slope is consistent with a dielectric
      continuum model of the solvated electron and the dielectric constant of the
      solid. The extrapolated IPs are compared with results obtained for negative
      ammonia cluster ions and metallic solutions in liquid ammonia. Differences are
      explained by the presence of counterions and their various distances from the
      solvated electron.

PMID- 15847460
TI  - Millimeter wave spectrum of bromomethyl radical, CH2Br.
AB  - The rotational spectra of the two isotopic species of the bromomethyl radical,
      CH2 79Br and CH2 81Br, have been observed in their ground electronic state 2B1 in
      the 180-470 GHz frequency region, corresponding to a-type transitions from N=8-7
      to N=21-20. The radical was produced by hydrogen abstraction of methylbromide
      (CH3Br) either by chlorine or by fluorine atoms in a free space cell. Hyperfine
      structure due to the bromine nucleus has been resolved in the observed spectra,
      and the rotational constants as well as the fine and hyperfine interaction
      constants were accurately determined for both isotopomers. The inertial defect
      was determined to be 0.028 96(20) and 0.028 95(20) amu A(2), for CH2 79Br and CH2
      81Br, respectively, suggesting a planar structure. By fixing the [angle]HCH bond
      angle at 124.5 degrees , an effective molecular structure can be derived as
      r0(CBr)=1.848 A and r0(CH)=1.084 A. A comparison of the molecular structure of
      various halogen-substituted methyl radicals with respect to the planarity of
      these radicals is discussed.

PMID- 15847461
TI  - Geometry and spin-multiplicity of half-sandwich type transition-metal-benzene
      complexes.
AB  - The low lying electronic states of 3d transition-metal-benzene complexes MBz
      (with M=Sc, V, and Ni) have been investigated by performing complete active space
      self-consistent field and multireference configuration interaction calculations.
      Geometries, energetics, and electronic structure are presented and discussed. The
      results concerning both the geometry and the spin multiplicity of the ground
      state contrast with those obtained from previous calculations based on density
      functional theory. The disagreements between single-reference-based approaches
      and multireference methods in the characterization of neutral 3d-metal complexes
      are discussed.

PMID- 15847462
TI  - High-level ab initio calculations for the four low-lying families of minima of
      (H2O)20. II. Spectroscopic signatures of the dodecahedron, fused cubes, face
      sharing pentagonal prisms, and edge-sharing pentagonal prisms hydrogen bonding
      networks.
AB  - We report the first harmonic vibrational spectra for each of the lowest lying
      isomers within the four major families of minima of (H2O)20, namely, the
      dodecahedron, fused cubes, face-sharing pentagonal prisms, and edge-sharing
      pentagonal prisms. These were obtained at the second-order Moller-Plesset
      perturbation level of theory (MP2) with the augmented correlation consistent
      basis set of double zeta quality (aug-cc-pVDZ) at the corresponding minimum
      energy geometries. The computed infrared (IR) spectra are the first ones obtained
      from first principles for these clusters. They were found to contain spectral
      features, which can be directly mapped onto the distinctive spectroscopic
      signatures of their constituent tetramer, pentamer, and octamer fragments. The
      dodecahedron spectra show the richest structure in the OH stretching region and
      are associated with the most redshifted OH vibrations with respect to the
      monomer. The lowest lying edge-sharing pentagonal prism isomer displays intense
      IR active vibrations that are redshifted by approximately 600 cm(-1) with respect
      to the water monomer. Furthermore the most redshifted, IR-active OH stretching
      vibrations for all four networks correspond to hydrogen bonded OH groups, which
      exhibit the following two common characteristics: (i) they belong to fragments
      which have a "free" OH stretch and (ii) they act as donors to a neighboring water
      molecule along a "dimerlike" (strong) hydrogen bond. The zero-point energy
      corrected MP2/CBS (complete basis set) limit binding energies D(0) for the four
      isomers are -163.1 kcal/mol (edge-sharing pentagonal prism), -160.1 kcal/mol
      (face-sharing pentagonal prism), -157.5 kcal/mol (fused cubes), and -148.1
      kcal/mol (dodecahedron).

PMID- 15847463
TI  - Coherent third-order spectroscopic probes of molecular chirality.
AB  - The third-order optical response of a system of coupled localized anharmonic
      vibrations is studied using a Green's function solution of the nonlinear exciton
      equations for bosonized excitons, which are treated as interacting
      quasiparticles. The explicit calculation of two-exciton states is avoided and the
      scattering of quasiparticles provides the mechanism of optical nonlinearities. To
      first-order in the optical wave vector we find several rotationally invariant
      tensor components for isotropic ensembles which are induced by chirality. The
      nonlocal nonlinear susceptibility tensor is calculated for infinitely large
      periodic structures in momentum space, where the problem size reduces to the
      exciton interaction radius. Applications are made to alpha and 3(10) helical
      infinite peptides.

PMID- 15847464
TI  - Protonated water clusters described by an empirical valence bond potential.
AB  - The properties of low-lying stationary points on the potential energy surfaces of
      singly protonated water clusters (H(2)O)(n)H(+), are investigated using an
      empirical valence bond potential. Candidate global minima are reported for n=2-4,
      8, and 20-22. For n=8, the variation in the energies and structures of low-lying
      minima with the number of valence bond states included in the model is studied.
      For n=4 and 8, disconnectivity graphs are also reported and are compared to
      results for the equivalent neutral water clusters as described by the rigid TIP3P
      potential. For the larger clusters, n=20-22, the structural properties of the low
      energy minima are compared with recently published spectroscopic data on these
      systems. The observed differences between the n=20 and n=21 systems are
      qualitatively reproduced by the model potential, but the similarities between the
      n=21 and n=22 systems are not.

PMID- 15847465
TI  - Ground-state properties and static dipole polarizabilities of the alkali dimers
      from K2 n to Fr2 n(n=0,+1) from scalar relativistic pseudopotential coupled
      cluster and density functional studies.
AB  - The newly adjusted energy-consistent nine-valence-electron pseudopotentials for K
      to Fr are used to calculate spectroscopic properties for the neutral and
      positively charged alkali dimers using coupled cluster and density functional
      theory. For the neutral dimers the static dipole polarizability was calculated.
      The coupled cluster results are all in excellent agreement with experimental
      values. The density functionals used can give quite different spectroscopic
      properties especially for the dipole polarizability, with the Perdew-Wang PW91
      functional performing best.

PMID- 15847466
TI  - A combined zero electronic kinetic energy spectroscopy and ion-pair dissociation
      imaging study of the F2 + (X 2Pi g) structure.
AB  - Rotationally resolved pulsed field ionization and zero electronic kinetic energy
      photoelectron spectra for the transition F(2) (+)(X (2)Pi(g))<--F(2)(X
      (1)Sigma(g) (+)) have been recorded using the extreme ultraviolet coherence
      radiation. The vibrational energy spacings, rotational constants, and spin orbit
      coupling constants for the first three vibrational states of F(2) (+)(X (2)Pi(g))
      have been determined accurately. The first adiabatic ionization potential (IP) of
      F(2) is determined as IP(F(2))=126 585.7+/-0.5 cm(-1). To determine the threshold
      E(tipp) for ion-pair production of F(2), the images of F(-)((1)S(0)) in the
      velocity mapping conditions have also been recorded at the photon energy of 126
      751 cm(-1). Taking the Stark effect into account, the E(tipp) is determined as
      E(tipp)(F(2))=126 045+/-8 cm(-1) (15.628+/-0.001 eV). By combing the IP(F(2)) and
      the E(tipp)(F(2)) determined in this work and together with the reported
      ionization potential and electronic affinity of the F atom, the bond dissociation
      energies of F(2) and F(2) (+) are determined as D(0)(F(2))=1.606+/-0.001 eV and
      D(0)(F(2) (+))=3.334+/-0.001 eV, respectively.

PMID- 15847467
TI  - Tunneling dynamics of double proton transfer in formic acid and benzoic acid
      dimers.
AB  - Direct dynamics calculations based on instanton techniques are reported of
      tunneling splittings due to double proton transfer in formic and benzoic acid
      dimers. The results are used to assign the observed splittings to levels for
      which the authors of the high-resolution spectra could not provide a definitive
      assignment. In both cases the splitting is shown to be due mainly to the zero
      point level rather than to the vibrationally or electronically excited level
      whose spectrum was investigated. This leads to zero-point splittings of 375 MHz
      for (DCOOH)(2) and 1107 MHz for the benzoic acid dimer. Thus, contrary to earlier
      calculations, it is found that the splitting is considerably larger in the
      benzoic than in the formic acid dimer. The calculations are extended to solid
      benzoic acid where the asymmetry of the proton-transfer potential induced by the
      crystal can be overcome by suitable doping. This has allowed direct measurement
      of the interactions responsible for double proton transfer, which were found to
      be much larger than those in the isolated dimer. To account for this observation
      both static and dynamic effects of the crystal forces on the intradimer hydrogen
      bonds are included in the calculations. The same methodology, extended to higher
      temperatures, is used to calculate rate constants for HH, HD, and DD transfers in
      neat benzoic acid crystals. The results are in good agreement with reported
      experimental rate constants measured by NMR relaxometry and, if allowance is made
      for small structural changes induced by doping, with the transfer matrix elements
      observed in doped crystals. Hence the method used allows a unified description of
      tunneling splittings in the gas phase and in doped crystals as well as of
      transfer rates in neat crystals.

PMID- 15847468
TI  - Internal dynamics features in the free jet rotational spectrum of the
      acetaldehyde-Kr molecular complex.
AB  - The structure and the dynamics of internal motions in the complex formed between
      acetaldehyde and Kr are studied by free jet absorption microwave spectroscopy
      performed in the range 60-78 GHz. The fourfold structure of each rotational line
      is evidence of the vibration-rotation coupling between the overall rotation of
      the complex, a tunneling motion of the Kr atom between two equivalent positions
      and the internal rotation of the methyl group in the acetaldehyde moiety. The
      four sets of transitions could be fitted with a coupled Hamiltonian which allows
      for the Coriolis interaction obtaining the energy separation between the
      vibrational energy levels related to the tunneling motion, while the observed
      splittings due to the methyl group internal rotation were analyzed independently
      with an appropriate model. The potential energy barriers for the tunneling motion
      and the internal rotation of the methyl group have been calculated and the
      interaction of the rare gas atom with the acetaldehyde moiety is reflected in the
      change of the V(3) barrier to internal rotation in going from the molecule to the
      weakly bound complex.

PMID- 15847469
TI  - Rotational spectrum, inversion, and geometry of 2,5-dihydrofuran...ethyne and a
      generalization about Z...H-C hydrogen bonds.
AB  - The ground-state rotational spectra of nine isotopomers of a complex formed
      between 2,5-dihydrofuran and ethyne were recorded with a pulsed-jet, Fourier
      transform microwave spectrometer. Rotational and centrifugal distortion constants
      were obtained for C4H6O...HCCH, C4H6O...DCCH, C4H6O...HCCD, C4H6O...DCCD, [3,4
      D2]-C4H6O...HCCH, C4H6O...H13CCH, C4H6O...HC13CH, , and [3(13C]-C4H6O...HCCH. The
      substituted species were studied in their natural abundances. For the more
      abundant isotopomers, weak c-type transitions as well as strong a-type
      transitions were observed. The primary intermolecular binding was shown to
      consist of a hydrogen bond formed by the ethyne subunit acting as the proton
      donor and the O atom of 2,5-dihydrofuran as the proton acceptor. The complex has
      a plane of symmetry that includes the O atom and the ethyne subunit, with a
      pyramidal configuration at oxygen. A fit of the principal moments of inertia of
      all nine isotopomers under the assumption of unperturbed 2,5-dihydrofuran and
      ethyne geometries yielded the values r(O...H)=2.127(8) A, phi=57.8(18) degrees ,
      and theta=16.2(32) degrees, where phi is the angle made by the HCCH subunit at O
      and theta is the angular deviation of the O...H-C nuclei from collinearity. This
      geometry is compared with those obtained by ab initio calculations conducted with
      a range of basis sets and with electron correlation taken into account at the MP2
      (Moller-Plesset second order) level of theory. A small inversion doubling
      (approximately equal to 20-30 kHz) of c-type transitions, well resolved only for
      the parent isotopomer and [3HCCH, was attributed to a vibrational motion that
      inverts the configuration at oxygen. A one-dimensional model for this motion was
      used with a double minimum potential energy function of the type
      V(phi)=alphaphi(4)+betaphi(2) to estimate the observed separation DeltaE(01) of
      the lowest pair (v=0 and v=1) of associated energy levels. The predicted
      DeltaE(01) had the same magnitude as that deduced from the inversion doubling of
      the c-type transitions. The geometry of C4H6O...HCCH is compared with those other
      B...HCCH, where B is vinyl fluoride, oxirane, and thiirane. A rationalization of
      the angular geometries of various B...HX, where X=F, Cl, Br, or CCH, is
      presented.

PMID- 15847470
TI  - Internal rotation in peroxynitrous acid (ONOOH).
AB  - Using higher levels of wave-function-based electronic structure theory than
      previously applied, as well as density functional theory (B-LYP and B3-LYP
      functionals), all theoretical models conclude that three ONOOH conformers are
      stationary point minima, in disagreement with some of the previous studies that
      we survey. In order of increasing energy, these are the cis-cis, cis-perp, and
      trans-perp conformers. Basis sets including diffuse functions seem to be needed
      to obtain a qualitatively correct representation of the internal rotation
      potential energy surface at higher levels of theory. Internal rotation about the
      peroxide bond involving the cis-cis, cis-gauche transition structure (TS), cis
      perp, and cis-trans TS conformers is studied in detail. To help ascertain the
      relative stability of the cis-perp conformer, multireference configuration
      interaction energy calculations are carried out, and rule of thumb estimates of
      multireference character in the ground-state wave functions of the ONOOH
      conformers are considered. CCSD(T)/aug-cc-pVTZ physical properties (geometries,
      rotational constants, electric dipole moments, harmonic vibrational frequencies,
      and infrared intensities) are compared with the analogous experimental data
      wherever possible, and also with density functional theory. Where such
      experimental data are nonexistent, the CCSD(T) and B3-LYP results are useful
      representations. For example, the electric dipole moment |mu(e)| of the cis-cis
      conformer is predicted to be 0.97+/-0.03 D. CCSD(T) energies, extrapolated to the
      aug-cc-pVNZ limit, are employed in isodesmic reaction schemes to derive zero
      Kelvin heats of formation and bond dissociation energies of the ONOOH stationary
      point minima. In agreement with recent gas-phase experiments, the peroxide bond
      dissociation energies of the cis-cis and trans-perp conformers are calculated as
      19.3+/-0.4 and 16.0+/-0.4 kcalmol, respectively. The lowest energy cis-cis
      conformer is less stable than nitric acid by 28.1+/-0.4 kcalmol at 0 K.

PMID- 15847471
TI  - Systematic ab initio studies of the conformers and conformational distribution of
      gas-phase tyrosine.
AB  - A full structural assignment of the conformers of gaseous tyrosine is presented.
      A total of 1296 unique trial structures were generated by allowing for all
      combinations of internal single-bond rotamers and optimized at the B3LYP6-311G*
      level of theory and then subjected to further optimization at the B3LYP6-311++G**
      level. A total of 76 conformers are found and their dipole moments, rotational
      constants, and harmonic frequencies are determined. Accurate relative energies
      are given at the MP26-311G(2df,p)B3LYP6-311++G** level of theory. Characteristic
      H-bonding types are classified and listed for all the conformers. The four most
      stable conformers display an intramolecular H bond, COOH...NH(2), and an
      additional H-bonding interaction between the amino group and pi electron of the
      aromatic ring. The results further confirm that the global minimum conformations
      of the aromatic amino acids have the same H-bonding type. Combined with
      statistical mechanics principles, conformational distributions at various
      temperatures are computed and the temperatures with which the theoretical results
      match that of experiments are indicated.

PMID- 15847472
TI  - Comparison of experimental time-of-flight spectra of the HF products from the
      F+H2 reaction with exact quantum mechanical calculations.
AB  - High resolution HF product time-of-flight spectra measured for the reactive
      scattering of F atoms from n-H2(p-H2) molecules at collision energies between 69
      and 81 meV are compared with exact coupled-channel quantum mechanical
      calculations based on the Stark-Werner ab initio ground state potential energy
      surface. Excellent agreement between the experimental and computed rotational
      distributions is found for the HF product vibrational states v'=1 and v'=2. For
      the v'=3 vibrational state the agreement, however, is less satisfactory,
      especially for the reaction with p-H2. The results for v'=1 and v'=2 confirm that
      the reaction dynamics for these product states is accurately described by the
      ground electronic state 1 (2)A' potential energy surface. The deviations for
      HF(v'=3, j' > or =2) are attributed to an enhancement of the reaction resulting
      from the 25% fraction of excited ((2)P(12)) fluorine atoms in the reactant beam.

PMID- 15847473
TI  - Potential energy surface for the CCl4 + H --> CCl3 + ClH reaction: kinetics and
      dynamics study.
AB  - An analytical potential energy surface for the gas-phase CCl4 + H --> CCl3 + ClH
      reaction was constructed with suitable functional forms to represent vibrational
      modes. This surface is completely symmetric with respect to the permutation of
      the four chlorine atoms and is calibrated with respect to experimental thermal
      rate constants available over the temperature range 297-904 K. On this surface,
      the thermal rate constants were calculated using variational transition-state
      theory with semiclassical transmission coefficients over a wider temperature
      range 300-2500 K, therefore obtaining kinetics information at higher temperatures
      than are experimentally available. This surface was also used to analyze
      dynamical features, such as tunneling and reaction-path curvature. In the first
      case, the influence of the tunneling factor is very small since a heavy chlorine
      atom has to pass through the barrier. In the second, it was found that
      vibrational excitation of the Cl-H stretching mode can be expected in the exit
      channel.

PMID- 15847474
TI  - Density functional calculations of molecular parity-violating effects within the
      zeroth-order regular approximation.
AB  - A (quasirelativistic) two-component density functional theory (DFT) approach to
      the computation of parity-violating energy differences between enantiomers is
      presented which is based on the zeroth-order regular approximation (ZORA). This
      approach is employed herein to compute parity-violating energy differences
      between several P and M conformations of dihydrogen dichalcogenides (H2X2 with
      X=O, S, Se, Te, Po), of which some compounds have recently been suggested as
      potential molecular candidates for the first experimental measurement of parity
      violating effects in chiral molecules. The DFT ZORA results obtained in this work
      with "pure" density functionals are anticipated to deviate by well less than 1%
      from data that would be computed within related (relativistic) four-component
      Dirac-Kohn-Sham-Coulomb schemes. In our implementation of the ZORA slightly
      larger relative deviations are expected for hybrid functionals, depending on the
      amount of "exact" exchange. For B3LYP (20% exact exchange) differences are
      estimated to amount to at most 3% in hydrogen peroxide, 2% in disulfane, and 1%
      or less for the heavier homologs. Thus, the present two-component approach is
      expected to perform excellently when compared to four-component density
      functional schemes while being at the same time computationally more efficient.
      The ZORA approach will therefore be of particular interest for the prediction of
      parity-violating vibrational frequency shifts, for instance, in isotopomers of
      H(2)Se(2) and H(2)Te(2).

PMID- 15847475
TI  - Evolution of the structure of amorphous ice: from low-density amorphous through
      high-density amorphous to very high-density amorphous ice.
AB  - We report results of molecular dynamics simulations of amorphous ice for
      pressures up to 22.5 kbar. The high-density amorphous ice (HDA) as prepared by
      pressure-induced amorphization of I(h) ice at T=80 K is annealed to T=170 K at
      various pressures to allow for relaxation. Upon increase of pressure, relaxed
      amorphous ice undergoes a pronounced change of structure, ranging from the low
      density amorphous ice at p=0, through a continuum of HDA states to the limiting
      very high-density amorphous ice (VHDA) regime above 10 kbar. The main part of the
      overall structural change takes place within the HDA megabasin, which includes a
      variety of structures with quite different local and medium-range order as well
      as network topology and spans a broad range of densities. The VHDA represents the
      limit to densification by adapting the hydrogen-bonded network topology, without
      creating interpenetrating networks. The connection between structure and
      metastability of various forms upon decompression and heating is studied and
      discussed. We also discuss the analogy with amorphous and crystalline silica.
      Finally, some conclusions concerning the relation between amorphous ice and
      supercooled water are drawn.

PMID- 15847476
TI  - A new lattice-based theory for hydrogen-bonding liquids in uniform electric
      fields.
AB  - We propose a new lattice-based, mean-field theory for predicting alignment of
      molecular dipoles and hydrogen bonds in liquids subject to uniform electric
      fields. The theory is presently restricted to liquids whose molecules possess one
      (proton) donor and one acceptor sites each, and wherein the H-bond axis is
      collinear with the dipole moments of the bonded molecules. The final expressions
      for hydrogen bond stoichiometry and polarization are free of lattice parameters,
      are interpretable using simple phenomenological arguments, and reduce to known
      limiting forms. The theory is applied to understand the internal structure of
      hydrogen cyanide in the liquid state at different electric fields.

PMID- 15847477
TI  - Photostimulated electron detrapping and the two-state model for electron
      transport in nonpolar liquids.
AB  - In common nonpolar liquids, such as saturated hydrocarbons, there is a dynamic
      equilibrium between trapped (localized) and quasifree (extended) states of the
      excess electron (the two-state model). Using time-resolved dc conductivity, the
      effect of 1064 nm laser photoexcitation of trapped electrons on the charge
      transport has been observed in liquid n-hexane and methylcyclohexane. The light
      promotes the electron from the trap into the conduction band of the liquid. From
      the analysis of the two-pulse, two-color photoconductivity data, the residence
      time of the electrons in traps has been estimated as ca. 8.3 ps for n-hexane and
      ca. 13 ps for methylcyclohexane (at 295 K). The rate of detrapping decreases at
      lower temperature with an activation energy of ca. 200 meV (280-320 K); the
      lifetime-mobility product for quasifree electrons scales linearly with the
      temperature. We suggest that the properties of trapped electrons in hydrocarbon
      liquids can be well accounted for using the simple spherical cavity model. The
      estimated localization time of the quasifree electron is 20-50 fs; both time
      estimates are in agreement with the "quasiballistic" model. This localization
      time is significantly lower than the value of 310+/-100 fs obtained using time
      domain terahertz (THz) spectroscopy for the same system [E. Knoesel, M. Bonn, J.
      Shan, F. Wang, and T. F. Heinz, J. Chem. Phys. 121, 394 (2004)]. We suggest that
      the THz signal originates from the oscillations of electron bubbles rather than
      the free-electron plasma; vibrations of these bubbles may be responsible for the
      deviations from the Drude behavior observed below 0.4 THz. Various implications
      of these results are discussed.

PMID- 15847478
TI  - Time- and frequency-resolved fluorescence spectra of nonadiabatic dissipative
      systems: what photons can tell us.
AB  - The monitoring of the excited-state dynamics by time- and frequency-resolved
      spontaneous emission spectroscopy has been studied in detail for a model
      exhibiting an excited-state curve crossing. The model represents characteristic
      aspects of the photoinduced ultrafast dynamics in large molecules in the gas or
      condensed phases and accounts for strong nonadiabatic and electron-vibrational
      coupling effects, as well as for vibrational relaxation and optical dephasing. A
      comprehensive overview of the dependence of spontaneous emission spectra on the
      characteristics of the excitation and detection processes (such as carrier
      frequencies, pump/gate pulse durations, as well as optical dephasing) is
      presented. A systematic comparison of ideal spectra, which provide simultaneously
      perfect time and frequency resolution and thus contain maximal information on the
      system dynamics, with actually measurable time- and frequency-gated spectra has
      been carried out. The calculations of real time- and frequency-gated spectra
      demonstrate that complementary information on the excited-state dynamics can be
      extracted when the duration of the gate pulse is varied.

PMID- 15847479
TI  - Effect of chemical structure on the isobaric and isochoric fragility in
      polychlorinated biphenyls.
AB  - Pressure-volume-temperature data, along with dielectric relaxation measurements,
      are reported for a series of polychlorinated biphenyls (PCB), differing in the
      number of chlorine atoms on their phenyl rings. Analysis of the results reveals
      that with increasing chlorine content, the relaxation times of the PCB become
      governed to a greater degree by density rho relative to the effect of temperature
      T. This result is consistent with the respective magnitudes of the scaling
      exponent gamma yielding superpositioning of the relaxation times measured at
      various temperatures and pressures, when plotted versus rho(gamma)/T. While at
      constant (atmospheric) pressure, fragilities for the various PCB are equivalent,
      the fragility at constant volume varies inversely with chlorine content.
      Evidently, the presence of bulkier chlorine atoms on the phenyl rings magnifies
      the effect which the density has on the relaxation dynamics.

PMID- 15847480
TI  - The role of solvent structure in the absorption spectrum of solvated electrons:
      mixed quantum/classical simulations in tetrahydrofuran.
AB  - In polar fluids such as water and methanol, the peak of the solvated electron's
      absorption spectrum in the red has been assigned as a sum of transitions between
      an s-like ground state and three nearly degenerate p-like excited states bound in
      a quasispherical cavity. In contrast, in weakly polar solvents such as
      tetrahydrofuran (THF), the solvated electron has an absorption spectrum that
      peaks in the mid-infrared, but no definitive assignment has been offered about
      the origins of the spectrum or the underlying structure. In this paper, we
      present the results of adiabatic mixed quantum/classical molecular dynamic
      simulations of the solvated electron in THF, and provide a detailed explanation
      of the THF-solvated electron's absorption spectrum and electronic structure.
      Using a classical solvent model and a fully quantum mechanical excess electron,
      our simulations show that although the ground and first excited states are bound
      in a quasispherical cavity, a multitude of other, nearby solvent cavities support
      numerous, nearly degenerate, bound excited states that have little Franck-Condon
      overlap with the ground state. We show that these solvent cavities, which are
      partially polarized so that they act as electron trapping sites, are an inherent
      property of the way THF molecules pack in the liquid. The absorption spectrum is
      thus assigned to a sum of bound-to-bound transitions between a localized ground
      state and multiple disjoint excited states scattered throughout the fluid.
      Furthermore, we find that the usual spherical harmonic labels (e.g., s-like, p
      like) are not good descriptors of the excited-state wave functions of the
      solvated electron in THF. Our observation of multiple disjoint excited states is
      consistent with femtosecond pump-probe experiments in the literature that suggest
      that photoexcitation of solvated electrons in THF causes them to relocalize into
      solvent cavities far from where they originated.

PMID- 15847481
TI  - Determination of photophysical parameters from photon arrival time trajectories
      in single molecule fluorescence spectroscopy.
AB  - Triplet blinking is a phenomenon observed commonly in single molecule
      fluorescence spectroscopy. At high to moderate excitation intensities one can
      distinguish bright (on) and dark (off) periods in the fluorescence intensity
      trajectory caused by sojourns into the nonemissive triplet state. In this work,
      we focus on triplet blinking of an immobilized molecule in the low excitation
      regime, where a threshold between on and off intensity levels cannot be set, and,
      therefore, a standard on/off analysis of fluorescence intensity trajectories is
      not possible. In the low excitation regime triplet blinking parameters can be
      recovered from photon arrival time trajectories, i.e., records of individual
      photon arrival time. We use computer-generated data to compare the recovery of
      the triplet blinking parameters from the intensity correlation function (ICF) and
      the histogram of interarrival time. We have found that the ICF offers a better
      statistics for the recovery of the triplet blinking parameters.

PMID- 15847483
TI  - Dynamics of propene adsorption on Ag001.
AB  - The interaction of propene with Ag(001) is investigated by high resolution
      electron energy loss spectroscopy and supersonic molecular beam methods under
      ultra high vacuum conditions. Propene adsorbs molecularly at 110 K and desorbs
      intact leaving a clean surface after annealing to 160 K. Two adsorption sites,
      characterized by slightly different vibrational modes, exist. The low frequency
      species is observed already at low coverage for molecules impinging at strongly
      hyperthermal energies while at lower translational energy it appears only at high
      coverage. The initial sticking probability S(0) decreases with increasing
      translational energy, as appropriate for nonactivated adsorption systems. The
      angle and energy dependence of S(0) indicate that scaling is intermediate between
      total and normal energy. From the coverage dependence of the sticking probability
      we infer that both a nonthermal intrinsic and a thermal extrinsic precursor
      exist.

PMID- 15847482
TI  - Solvation free energies of amino acid side chain analogs for common molecular
      mechanics water models.
AB  - Quantitative free energy computation involves both using a model that is
      sufficiently faithful to the experimental system under study (accuracy) and
      establishing statistically meaningful measures of the uncertainties resulting
      from finite sampling (precision). In order to examine the accuracy of a range of
      common water models used for protein simulation for their solute/solvent
      properties, we calculate the free energy of hydration of 15 amino acid side chain
      analogs derived from the OPLS-AA parameter set with the TIP3P, TIP4P, SPC, SPC/E,
      TIP3P-MOD, and TIP4P-Ew water models. We achieve a high degree of statistical
      precision in our simulations, obtaining uncertainties for the free energy of
      hydration of 0.02-0.06 kcal/mol, equivalent to that obtained in experimental
      hydration free energy measurements of the same molecules. We find that TIP3P-MOD,
      a model designed to give improved free energy of hydration for methane, gives
      uniformly the closest match to experiment; we also find that the ability to
      accurately model pure water properties does not necessarily predict ability to
      predict solute/solvent behavior. We also evaluate the free energies of a number
      of novel modifications of TIP3P designed as a proof of concept that it is
      possible to obtain much better solute/solvent free energetic behavior without
      substantially negatively affecting pure water properties. We decrease the average
      error to zero while reducing the root mean square error below that of any of the
      published water models, with measured liquid water properties remaining almost
      constant with respect to our perturbations. This demonstrates there is still both
      room for improvement within current fixed-charge biomolecular force fields and
      significant parameter flexibility to make these improvements. Recent research in
      computational efficiency of free energy methods allows us to perform simulations
      on a local cluster that previously required large scale distributed computing,
      performing four times as much computational work in approximately a tenth of the
      computer time as a similar study a year ago.

PMID- 15847484
TI  - The importance of tunneling in the first hydrogenation step in ammonia synthesis
      over a Ru(0001) surface.
AB  - The hydrogenation of nitrogen (N(ads)+H(ads)-->NH(ads)) on metal surfaces is an
      important step in ammonia catalysis. We investigate the reaction dynamics of this
      hydrogenation step by time independent scattering theory and variational
      transition state theory (VTST) including tunneling corrections. The potential
      energy surface is derived by hybrid density functional theory on a model cluster
      composed of 12 ruthenium atoms resembling a Ru(0001) surface. The scattering
      calculations are performed on a reduced dimensionality potential energy
      hypersurface, where two dimensions are treated explicitly and all others are
      included implicitly by the zero-point correction. The VTST calculations include
      quantum effects along the reaction coordinate by applying the small curvature
      tunneling scheme. Even at room temperature (where ruthenium already shows
      catalytic activity) we find rate enhancement by tunneling by a factor of
      approximately 70. Inspection of the reaction probabilities shows that the major
      contribution to reactivity comes from the vibrational ground state of the
      reactants into vibrationally excited product states. The reaction rates are
      higher than determined in previous studies, and are compatible with experimental
      overall rates for ammonia synthesis.

PMID- 15847485
TI  - Structure of concentrated nanoemulsions.
AB  - We use extreme shear to create a dispersion of nanoscale droplets of silicone oil
      in an immiscible water phase containing an anionic surfactant sodium
      dodecylsulfate. Using centrifugal size fractionation, we obtain nanoemulsions
      having a well-defined average radius of a=75 nm. We measure the structure of
      concentrated nanoemulsions over a wide range of volume fractions, 0<phi<0.6,
      using small angle neutron scattering, and we determine the structure factor S(q)
      of disordered glassy dispersions of uniform deformable droplets interacting
      through screened surface charge repulsions. Although the low-q behavior of
      S(q,phi) resembles that predicted for hard spheres, the height of the primary
      peak does not. Instead, it exhibits a maximum as phi is increased. This
      difference cannot be explained solely by the droplet size polydispersity and is
      likely related to the deformability of the droplets that have been locked into a
      glassy structure.

PMID- 15847486
TI  - Selective internal manipulation of a single molecule by scanning tunneling
      microscopy.
AB  - We have studied the adsorption of the polyaromatic molecule 1,4"
      paratriphenyldimethylacetone, which we have nicknamed Trima. The originality of
      this linear molecule is that it was designed and synthesized to have two
      functionalities. First, chemisorb itself to the surface by its two ends rather
      like a bridge. Second, the central part of the molecule could then be rotated by
      injecting electrons with the tip of the scanning tunneling microscope (STM). The
      length of the molecule corresponds exactly to the spacing between five dimers in
      a row on the Si(100)-2 x 1 surface. We found that the molecule adsorbs as
      expected on the clean silicon surface by using complementary STM and synchrotron
      radiation studies. Manipulation of individual molecules with the STM tip showed
      selective internal modifications that were highly voltage dependent. These
      manipulations were found to be compatible with an electronic excitation of the pi
      pi* transition of the molecule.

PMID- 15847487
TI  - Reentrant onset of chaos in tubular image states.
AB  - We investigate the reentrant onset of chaos in "tubular image states," which are
      loosely bound states of electrons formed in the vicinity (20-40 nm) of conducting
      nanotubes. Chaos is shown to arise when an electron is placed in the vicinity of
      two metallic nanotubess with a magnetic field applied along the tubes. At
      stronger magnetic fields B approximately 10 T, we observe the formation of Landau
      like states encircling the two-tube system, which wipe out the chaos. We can
      reinstall the chaos by charging oppositely the nanotubes, thus breaking the
      symmetry of the system and correspondingly the shape of the Landau-like states.
      Detailed analysis of the onset of chaos is done by studying the statistical
      properties of the eigenvalues spectrum and by investigating the spatial
      autocorrelation functions of individual eigenstates.

PMID- 15847488
TI  - Quantitative measure of nanoscale adhesion hysteresis by ultrasonic force
      microscopy.
AB  - Adhesion hysteresis is the difference between the work used on separating two
      surfaces and the work gained on bringing them back together. Although much effort
      has been invested into adhesion hysteresis investigations at macroscales and
      microscales, its measurements at the nanolengths or even molecular lengths are
      still not easy. In this paper we demonstrate how to obtain quantitative measures
      of local adhesion hysteresis from ultrasonic force microscopy investigations. We
      derive analytical models fitting all the experimental cases and apply them to
      experimental data.

PMID- 15847489
TI  - Targeted molecular dynamics of an open-state KcsA channel.
AB  - Pore opening of KcsA channel is studied using targeted molecular dynamics
      simulations. Conformational changes of the protein are determined, starting from
      the crystallized refined 2.0 A structure (pdb 1K4C) determined in x-ray
      experiments and arriving to the open-state structure constructed on the basis of
      electron paramagnetic resonance spectroscopic data (pdb 1JQ1). Our results
      corroborate the essential role played by the terminal residues located on the
      transmembrane helices M2 which were not taken into account at that time. The
      aperture mechanism of the channel appears to be ziplike. A small constraint
      (approximately equal to 5 x 10(-2) kcal mol(-1) A(-2) per C(alpha)) applied to
      the terminal residues located on the intracellular side is sufficient to
      initialize the pore opening at the innermost part of the gate, but additional
      constraint must be applied to definitely complete the pore aperture. The open
      structure is proved to be a metastable state since releasing the constraint leads
      to another relaxed open conformation which seems to reach stability.

PMID- 15847490
TI  - Effects of internal noise for rate oscillations during CO oxidation on platinum
      surfaces.
AB  - We have studied the influence of internal noise on the reaction rate oscillation
      during carbon-monoxide oxidation on single crystal platinum surfaces using
      chemical Langevin equations. Considering that the surface is divided into small
      well-mixed cells, we have focused on the dynamic behavior inside a single cell.
      Internal noise can induce rate oscillations and the performance of the stochastic
      rate oscillations shows double maxima with the variation of the internal noise
      intensity, demonstrating the occurrence of internal noise coherent biresonance.
      The relationship between such a phenomenon with the deterministic bifurcation
      features of the system is also discussed.

PMID- 15847491
TI  - Mechanism of the CO oxidation reaction on O-precovered Pt(111) surfaces studied
      with near-edge x-ray absorption fine structure spectroscopy.
AB  - The mechanism of CO oxidation reaction on oxygen-precovered Pt(111) surfaces has
      been studied by using time-resolved near-edge x-ray absorption fine structure
      spectroscopy. The whole reaction process is composed of two distinct paths: (1) a
      reaction of isolated oxygen atoms with adsorbed CO, and (2) a reaction of island
      periphery oxygen atoms after the CO saturation. CO coadsorption plays a role to
      induce the dynamic change in spatial distribution of O atoms, which switches over
      the two reaction paths. These mechanisms were confirmed by kinetic Monte Carlo
      simulations. The effect of coadsorbed water in the reaction mechanism was also
      examined.

PMID- 15847492
TI  - Phase coexistence in heterogeneous porous media: a new extension to Gibbs
      ensemble Monte Carlo simulation method.
AB  - The effect of confinement on phase behavior of simple fluids is still an area of
      intensive research. In between experiment and theory, molecular simulation is a
      powerful tool to study the effect of confinement in realistic porous materials,
      containing some disorder. Previous simulation works aiming at establishing the
      phase diagram of a confined Lennard-Jones-type fluid, concentrated on simple pore
      geometries (slits or cylinders). The development of the Gibbs ensemble Monte
      Carlo technique by Panagiotopoulos [Mol. Phys. 61, 813 (1987)], greatly favored
      the study of such simple geometries for two reasons. First, the technique is very
      efficient to calculate the phase diagram, since each run (at a given temperature)
      converges directly to an equilibrium between a gaslike and a liquidlike phase.
      Second, due to volume exchange procedure between the two phases, at least one
      invariant direction of space is required for applicability of this method, which
      is the case for slits or cylinders. Generally, the introduction of some disorder
      in such simple pores breaks the initial invariance in one of the space directions
      and prevents to work in the Gibbs ensemble. The simulation techniques for such
      disordered systems are numerous (grand canonical Monte Carlo, molecular dynamics,
      histogram reweighting, N-P-T+test method, Gibbs-Duhem integration procedure,
      etc.). However, the Gibbs ensemble technique, which gives directly the
      coexistence between phases, was never generalized to such systems. In this work,
      we focus on two weakly disordered pores for which a modified Gibbs ensemble Monte
      Carlo technique can be applied. One of the pores is geometrically undulated,
      whereas the second is cylindrical but presents a chemical variation which gives
      rise to a modulation of the wall potential. In the first case almost no change in
      the phase diagram is observed, whereas in the second strong modifications are
      reported.

PMID- 15847493
TI  - A temperature-programmed time-of-flight secondary ion mass spectroscopy study of
      intermixing of amorphous ethanol and heavy-water films at 15-200 K.
AB  - On the basis of time-of-flight secondary ion mass spectrometry, the
      intermolecular interactions of amorphous ethanol and heavy-water films have been
      investigated in terms of the translational molecular diffusion, hydrogen-bond
      reorganization, and isotope scrambling. The morphology of the ethanol film (heavy
      water film) changes at 120 K (165 K), and the isotope scrambling takes place
      between the ethanol and heavy-water molecules above 140 K. The intermixing of the
      layered binary films of ethanol and heavy water is induced at 120 K as a
      consequence of the increased mobility of the ethanol molecules but the mixing is
      incomplete at the molecular level. The complete mixing occurs above 140-150 K
      provided that the highly mobile water molecules emerge. It is concluded that the
      viscous liquid phase evolves above the conventional glass-transition temperatures
      (97 and 136 K for ethanol and heavy water, respectively), which is followed by
      the drastic morphological change (120 and 165 K) as a consequence of the
      increased fluidity of the films.

PMID- 15847494
TI  - Enhancement of nitrogen physisorption in coadsorption with oxygen on free,
      positively charged silver clusters.
AB  - The coadsorption of molecular nitrogen and oxygen on small cationic silver
      clusters in the gas phase is experimentally studied. The presence of oxygen
      enhances the adsorption probabilities of N2. This indicates a partial charge
      transfer out of the finite free electron reservoir of the small silver particles
      into the chemisorbed oxygen molecule.

PMID- 15847495
TI  - Spectrally- and time-resolved vibrational surface spectroscopy: ultrafast
      hydrogen-bonding dynamics at D2O/CaF2 interface.
AB  - Time- and frequency-domain three-wave mixing spectroscopy (IR+visible sum
      frequency generation) is developed as the lowest-order nonlinear technique that
      is both surface selective and capable of measuring spectral evolution of
      vibrational coherences. Using 70 fs infrared and 40 fs visible pulses, we observe
      ultrafast spectral dynamics of the OD stretch of D2O at the CaF2 surface.
      Spectral shifts indicative of the hydrogen-bond network rearrangement occur on
      the 100 fs time scale, within the observation time window determined by the
      vibrational dephasing. By tuning the IR pulse wavelength to the blue or red side
      of the OD-stretch transition, we selectively monitor the dynamics of different
      subensembles in the distribution of the H-bond structures. The blue-side
      excitation (weaker H-bonding structures) shows monotonic decay and nu(OD)
      frequency shift to the red on a 100 fs time scale, which is better described by a
      Gaussian than an exponential frequency correlation function. In contrast, the red
      side excitation (stronger H-bonding structures) results in a blue spectral shift
      and a recursion in the signal at 125+/-10 fs, indicating the presence of an
      underdamped intermolecular mode of interfacial water.

PMID- 15847496
TI  - Structure and stability of chiral beta-tapes: a computational coarse-grained
      approach.
AB  - We present two coarse-grained models of different levels of detail for the
      description of beta-sheet tapes obtained from equilibrium self-assembly of short
      rationally designed oligopeptides in solution. Here we only consider the case of
      the homopolymer oligopeptides with the identical sidegroups attached, in which
      the tapes have a helicoid surface with two equivalent sides. The influence of the
      chirality parameter on the geometrical characteristics, namely the diameter,
      interstrand distance, and pitch, of the tapes has been investigated. The two
      models are found to produce equivalent results suggesting a considerable degree
      of universality in conformations of the tapes.

PMID- 15847497
TI  - Molecular simulation of surfactant-assisted protein refolding.
AB  - Protein refolding to its native state in vitro is a challenging problem in
      biotechnology, i.e., in the biomedical, pharmaceutical, and food industry.
      Protein aggregation and misfolding usually inhibit the recovery of proteins with
      their native states. These problems can be partially solved by adding a
      surfactant into a suitable solution environment. However, the process of this
      surfactant-assisted protein refolding is not well understood. In this paper, we
      wish to report on the first-ever simulations of surfactant-assisted protein
      refolding. For these studies, we defined a simple model for the protein and the
      surfactant and investigated how a surfactant affected the folding behavior of a
      two-dimensional lattice protein molecule. The model protein and model surfactant
      were chosen such that we could capture the important features of the folding
      process and the interaction between the protein and the surfactant, namely, the
      hydrophobic interaction. It was shown that, in the absence of surfactants, a
      protein in an "energy trap" conformation, i.e., a local energy minima, could not
      fold into the native form, which was characterized by a global energy minimum.
      The addition of surfactants created folding pathways via the formation of protein
      surfactant complexes and thus enabled the conformations that fell into energy
      trap states to escape from these traps and to form the native proteins. The
      simulation results also showed that it was necessary to match the hydrophobicity
      of surfactant to the concentration of denaturant, which was added to control the
      folding or unfolding of a protein. The surfactants with different hydrophobicity
      had their own concentration range on assisting protein refolding. All of these
      simulations agreed well with experimental results reported elsewhere, indicating
      both the validity of the simulations presented here and the potential application
      of the simulations for the design of a surfactant on assisting protein refolding.

PMID- 15847498
TI  - Dynamical scaling of single chains on adsorbing substrates: diffusion processes.
AB  - We study the dynamics of tethered chains of length N on adsorbing surfaces,
      considering the dilute case; for this we use the bond fluctuation model and
      scaling concepts. In particular, we focus on the mean-square displacement of
      single monomers and of the center of mass of the chains. The characteristic time
      tau of the fluctuations of a free chain in a good solvent grows as tau
      approximately N(a), where the coefficient a obeys a=2nu+1. We show that the same
      coefficient also holds at the critical point of adsorption. At intermediate time
      scales single monomers show subdiffusive behavior; this concurs with the behavior
      calculated from scaling arguments based on the dynamical exponent a. In the
      adsorbed state tau(perpendicular), the time scale for the relaxation in the
      direction perpendicular to the surface, becomes independent of N;
      tau(perpendicular) is then the relaxation time of an adsorption blob. In the
      direction parallel to the surface the motion is similar to that of a two
      dimensional chain and is controlled by a time scale given by tau(parallel)
      approximately N(2nu(2)+1)L(-2Delta(nu/nu)), where nu(2) is the Flory exponent in
      two dimensions, nu is the Flory exponent in three dimensions, and Deltanu=nu(2)
      nu. For the motion parallel to the surface we find dynamical scaling over a range
      of about four decades in time.

PMID- 15847499
TI  - Corrections to scaling and crossover from good- to theta-solvent regimes of
      interacting polymers.
AB  - We exploit known properties of universal ratios, involving the radius of gyration
      R(g), the second and third virial coefficients B(2) and B(3), and the effective
      pair potential between the centers of mass of self-avoiding polymer chains with
      nearest-neighbor attraction, as well as Monte Carlo simulations, to investigate
      the crossover from good- to theta-solvent regimes of polymers of finite length L.
      The scaling limit and finite-L corrections to scaling are investigated in the
      good-solvent case and close to the theta temperature. Detailed interpolation
      formulas are derived from Monte Carlo data and results for the Edwards two
      parameter model, providing estimates of universal ratios as functions of the
      observable ratio A(2)=B(2)/R(g) (3) over the whole temperature range, from the
      theta point to the good-solvent regime. The convergence with L (L< or =8000) is
      found to be satisfactory under good-solvent conditions, but longer chains would
      be required to match theoretical predictions near the theta point, due to
      logarithmic corrections. A quantitative estimate of the universal ratio
      A(3)=B(3)/R(g) (6) as a function of temperature shows that the third virial
      coefficient remains positive throughout, and goes through a pronounced minimum at
      the theta temperature, which goes to zero as 1/ln L in the scaling limit.

PMID- 15847500
TI  - Capillary waves in a colloid-polymer interface.
AB  - The structure and the statistical fluctuations of interfaces between coexisting
      phases in the Asakura-Oosawa model [J. Chem. Phys. 22, 1255 (1954)] for a colloid
      polymer mixture are analyzed by extensive Monte Carlo simulations. We make use of
      a recently developed grand canonical cluster move with an additional constraint
      stabilizing the existence of two interfaces in the (rectangular) box that is
      simulated. Choosing very large systems, of size L x L x D with L=60 and D=120,
      measured in units of the colloid radius, the spectrum of capillary wave-type
      interfacial excitations is analyzed in detail. The local position of the
      interface is defined in terms of a (local) Gibbs surface concept. For small wave
      vectors capillary wave theory is verified quantitatively, while for larger wave
      vectors pronounced deviations show up. When one analyzes the data in terms of the
      concept of a wave vector-dependent interfacial tension, a monotonous decrease of
      this quantity with increasing wave vector is found. Limitations of our analysis
      are critically discussed.

PMID- 15847501
TI  - An in situ study of the t-butyllithium initiated polymerization of butadiene in d
      heptane via small angle neutron scattering and 1H-NMR.
AB  - We present a combined 1H-NMR and small angle neutron scattering in situ study of
      the anionic polymerization of butadiene using t-butyllithium as the initiator.
      Both initiation and propagation phases were explored. This combined approach
      allows the structural and kinetic characteristics to be accessed and cross
      compared. The use of the D22 instrument (ILL Grenoble) permits the attainment of
      Q approximately equal to 2 x 10(-3) A. This, in turn, led to the identification
      of coexisting large-scale and smaller aggregates during all stages of the
      polymerization. The smaller aggregates contain most of the reacted monomers.
      Their structure changes from high functionality wormlike chains at early stages
      of the reaction to starlike aggregates where the crossover occurs at a degree of
      polymerization of approximately equal to 40. The initiation event involved these
      small, high functionality (approximately equal to 120) aggregates that apparently
      consisted of cross-associated t-butyllithium with the newly formed allylic
      lithium head groups. As the initiation event progressed the initiation rate
      increased while the functionality of these small aggregates decreased and their
      size increased. Propagation, in the absence of initiation, was found to have a
      rate constant that was molecular weight dependent. At approximately 11 kg/mol the
      measured polymerization rate was found to increase while no further structural
      changes were seen.

PMID- 15847502
TI  - Longitudinal polarizability of long polymeric chains: quasi-one-dimensional
      electrostatics as the origin of slow convergence.
AB  - The longitudinal linear polarizability alpha(N) of a stereoregular oligomer of
      size N is proportional to N in the large-N limit, provided the system is
      nonconducting in that limit. It has long been known that the convergence of
      alpha(N)/N to the asymptotic alpha(infinity) value is slow. We show that the
      leading term in the difference between alpha(N)/N and alpha(infinity) is of the
      order of 1/N. The difference [alpha(N)-alpha(N-1)], as well as alpha(center)(N)
      (when computationally accessible), also converge to alpha(infinity), but faster,
      the leading term being of the order of 1/N(2). We also present evidence that in
      these cases the power law convergence behavior is due to quasi-one-dimensional
      electrostatics, with one exception. Specifically, in molecular systems the
      difference between alpha(N)/N and alpha(infinity) has not just one but two
      sources of the O(1/N) term, with one being due to the aforementioned Coulomb
      interactions, and the second due to the short ranged exponentially decaying
      perturbations on chain ends. The major role of electrostatics in the convergence
      of the remainders is demonstrated by means of a Clausius-Mossotti-type classical
      model. The conclusions derived from the model are also shown to be applicable in
      molecular systems, by means of test-case ab initio calculations on linear stacks
      of H(2) molecules, and on polyacetylene chains. The implications of the modern
      theory of polarization for extended systems are also discussed.

PMID- 15847503
TI  - Lattice Monte Carlo simulations of a charged polymer chain: effect of valence and
      concentration of the added salt.
AB  - The configurational properties of a single polyelectrolyte chain accompanied by
      counterions and added salt are simulated using the cooperative motion algorithm
      on the face-centered cubic lattice. In particular, a greater emphasis is put on
      the effect of valence z(s) and concentration of the added positive (negative)
      salt ions n(s) on the polymer behavior. This is achieved by inspecting two
      families of systems with widely varying numbers n(s) of monovalent (z(s)=1) or
      multivalent (z(s)=4) salt ions at two fixed reduced temperatures T*=0.5, 1. The
      calculations indicate that especially at the lower temperature the addition of
      some amount of multivalent salt has a tremendous impact on chain conformations
      compared to the situation with monovalent salt. Even for relatively low
      concentrations of the former, the mean radius of gyration <s2>(1/2) and the mean
      end-to-end distance <R2>(1/2) decrease sharply, i.e., the polymer exists in
      strongly collapsed forms. This reduction of polymer size is also accompanied by a
      drop in the system inner energy e* and the effective mean charge per monomer q*.
      The analysis of various pair-correlation functions g(ab)(r) indicates that the
      latter effect-caused by condensation of ions onto the chain-is dominated by the
      multivalent ones. Furthermore, it is found that for z(s)=4, the uncondensed salt
      ions tend to group themselves into small clusters.

PMID- 15847504
TI  - Molecular dynamics simulations of grafted polyelectrolytes on two apposing walls.
AB  - Molecular dynamics simulations of polyelectrolytes grafted to two apposing
      surfaces were performed. Bead-spring polymer models are used to treat flexible
      chains [e.g., sodium poly(styrene sulfonate)] and stiff chains (double-stranded
      DNA). The counterions are explicitly treated. The effect of the surface density
      of the grafted polymer, the chain length, and the gap width on the structure and
      the pressure were studied. Results are compared to experimental measurements and
      to simulations of polyelectrolyte brushes on a single surface. The density
      profiles exhibit a maximum not found in single surface data. The maximum is due
      to the brushes shrinking to avoid interpenetration.

PMID- 15847505
TI  - Molecular dynamics simulations of polymer transport in nanocomposites.
AB  - Molecular dynamics simulations on the Kremer-Grest bead-spring model of polymer
      melts are used to study the effect of spherical nanoparticles on chain diffusion.
      We find that chain diffusivity is enhanced relative to its bulk value when
      polymer-particle interactions are repulsive and is reduced when polymer-particle
      interactions are strongly attractive. In both cases chain diffusivity assumes its
      bulk value when the chain center of mass is about one radius of gyration R(g)
      away from the particle surface. This behavior echoes the behavior of polymer
      melts confined between two flat surfaces, except in the limit of severe
      confinement where the surface influence on polymer mobility is more pronounced
      for flat surfaces. A particularly interesting fact is that, even though chain
      motion is strongly speeded up in the presence of repulsive boundaries, this
      effect can be reversed by pinning one isolated monomer onto the surface. This
      result strongly stresses the importance of properly specifying boundary
      conditions when the near surface dynamics of chains are studied.

PMID- 15847506
TI  - Intermolecular self-interaction energies of magic clusters MAu4 (M=Ti and Zr).

PMID- 15847507
TI  - A new action photoelectron spectroscopy for anions.
AB  - We present a new experimental approach, in which anion photodetachment
      spectroscopy is recorded with electrons of fixed kinetic energy. This approach
      circumvents some shortcomings of the zero electron kinetic energy method. Our
      method is based on a modified magnetic bottle photoelectron spectrometer (MBPES).
      A tunable laser is used to detach electrons from mass selected anions, drifting
      collinearly with the 40 cm MBPES drift tube. To avoid Doppler broadening, a low
      voltage pulse removes the velocity component of anions from the detached
      electrons. Spectra are recorded by collecting the wavelength dependence of
      electron-signal at a predetermined TOF window, corresponding to a specific
      electron-kinetic energy. We call this approach PEACE, denoting photoelectron
      action spectroscopy at constant kinetic energy. Our best resolution is 0.65 meV
      for 1.5 meV electrons. We present a PEACE spectrum of HgCl(-) together with the
      corresponding simulated theoretical spectrum. The method is similar in resolution
      and data collection rates to the slow electron velocity map imaging technique
      recently introduced by Neumark and co-workers.

PMID- 15847508
TI  - An elementary derivation of the hard/soft-acid/base principle.
AB  - The hard/soft-acid/base (HSAB) principle indicates that hard acids prefer binding
      to hard bases (often forming bonds with substantial ionic character) while soft
      acids prefer binding to soft bases (often forming bonds with substantial covalent
      character). Though the HSAB principle is a foundational concept of the modern
      theory of acids and bases, the theoretical underpinnings of the HSAB principle
      remain murky. This paper examines the exchange reaction, wherein two molecules,
      one the product of reacting a hard acid and a soft base and the other the product
      of reacting a soft acid with a hard base, exchange substituents to form the
      preferred hard-hard and soft-soft product. A simple derivation shows that this
      reaction is exothermic, proving the validity of the HSAB principle. The analysis
      leads to the simple and conceptually appealing conclusion that the HSAB principle
      is a driven by simple electron transfer effects.

PMID- 15847509
TI  - Photo-induced chirality switching in a cobaloxime complex crystal.
AB  - Switching of molecular chirality under photo-irradiation was studied in a
      cobaloxime complex crystal. Excitation of the d-d transition of the Co(III) ion
      appeared to be much more effective in inducing the chirality change than
      excitation of the ligand-metal charge transfer band although the latter is more
      effective in breaking the Co-C bond that initiates the chirality switching. The
      chirality change versus irradiation time showed a steplike behavior suggesting
      that chirality switching of molecules occurred in correlation with their nearest
      neighbors.

PMID- 15847510
TI  - Plane wave/pseudopotential implementation of excited state gradients in density
      functional linear response theory: a new route via implicit differentiation.
AB  - This work presents the formalism and implementation of excited state nuclear
      forces within density functional linear response theory using a plane wave basis
      set. An implicit differentiation technique is developed for computing
      nonadiabatic coupling between Kohn-Sham molecular orbital wave functions as well
      as gradients of orbital energies which are then used to calculate excited state
      nuclear forces. The algorithm has been implemented in a plane
      wave/pseudopotential code taking into account only a reduced active subspace of
      molecular orbitals. It is demonstrated for the H(2) and N(2) molecules that the
      analytical gradients rapidly converge to the exact forces when the active
      subspace of molecular orbitals approaches completeness.

PMID- 15847511
TI  - Application of numerical basis sets to hydrogen bonded systems: a density
      functional theory study.
AB  - We have investigated and compared the ability of numerical and Gaussian-type
      basis sets to accurately describe the geometries and binding energies of a
      selection of hydrogen bonded systems that are well studied theoretically and
      experimentally. The numerical basis sets produced accurate results for geometric
      parameters but tended to overestimate binding energies. However, a comparison of
      the time taken to optimize phosphinic acid dimer, the largest complex considered
      in this study, shows that calculations using numerical basis sets offer a
      definitive advantage where geometry optimization of large systems is required.

PMID- 15847512
TI  - Continuum states from time-dependent density functional theory.
AB  - Linear response time-dependent density functional theory is used to study low
      lying electronic continuum states of targets that can bind an extra electron.
      Exact formulas to extract scattering amplitudes from the susceptibility are
      derived in one dimension. A single-pole approximation for scattering phase shifts
      in three dimensions is shown to be more accurate than static exchange for singlet
      electron-He(+) scattering.

PMID- 15847513
TI  - Electron density distribution in stacked benzene dimers: a new approach towards
      the estimation of stacking interaction energies.
AB  - The potential energy surface for the benzene dimer in stacked conformations (84
      points calculated) was computed at the MP2(FC)6-31+G(2d,2p) level of theory.
      Electron density (ED) distribution computed using the MP2(FC), B3LYP, and Hartree
      Fock methods with the same basis set is studied in the frame of topological
      analysis. It is found that ED topology does not depend on the method of
      calculation. The values of the ED and its Laplacian in the cage critical point
      calculated using different methods are determined to be linearly dependent with
      the slope depending on basis set. Correlation equations based on these properties
      allow the interaction energy between benzene rings to be predicted with 8% mean
      relative error in the energy for the given region of the potential energy
      surface. This provides a new method for the estimation of stacking interaction
      energy using ED properties calculated with low level quantum-chemical methods.

PMID- 15847514
TI  - A linear-scaling self-consistent generalization of the multistate empirical
      valence bond method for multiple excess protons in aqueous systems.
AB  - An extension to the multistate empirical valence bond (MS-EVB) method is
      presented in this paper that is capable of treating multiple excess protons
      within the context of molecular-dynamics simulation. The computational cost of
      the method scales linearly with respect to the number of excess protons.
      Calculations for a 0.44 M HCl systems are carried out to illustrate the
      multiproton extension of the MS-EVB method. A significant decrease in the Eigen
      type H(9)O(4)(+) cation is observed in the contact ion-pair configuration formed
      between Cl(-) and hydronium ions.

PMID- 15847515
TI  - An approximate but fast method to impose flexible distance constraints in
      molecular dynamics simulations.
AB  - A fast but approximative method to apply flexible constraints to bond lengths in
      molecular dynamics simulations is presented and the effects of the approximation
      are investigated. The method is not energy conserving, but coupling to a
      temperature bath results in stable simulations. The high frequencies from bond
      length vibrations are successfully removed from the system while maintaining the
      flexibility of the bonds. As a test liquid neopentane is simulated at different
      pressures. Energetic and dynamic properties are not affected by the new flexible
      constraint simulation method.

PMID- 15847516
TI  - Comparison of efficiency and bias of free energies computed by exponential
      averaging, the Bennett acceptance ratio, and thermodynamic integration.
AB  - Recent work has demonstrated the Bennett acceptance ratio method is the best
      asymptotically unbiased method for determining the equilibrium free energy
      between two end states given work distributions collected from either equilibrium
      and nonequilibrium data. However, it is still not clear what the practical
      advantage of this acceptance ratio method is over other common methods in
      atomistic simulations. In this study, we first review theoretical estimates of
      the bias and variance of exponential averaging (EXP), thermodynamic integration
      (TI), and the Bennett acceptance ratio (BAR). In the process, we present a new
      simple scheme for computing the variance and bias of many estimators, and
      demonstrate the connections between BAR and the weighted histogram analysis
      method. Next, a series of analytically solvable toy problems is examined to shed
      more light on the relative performance in terms of the bias and efficiency of
      these three methods. Interestingly, it is impossible to conclusively identify a
      "best" method for calculating the free energy, as each of the three methods
      performs more efficiently than the others in at least one situation examined in
      these toy problems. Finally, sample problems of the insertion/deletion of both a
      Lennard-Jones particle and a much larger molecule in TIP3P water are examined by
      these three methods. In all tests of atomistic systems, free energies obtained
      with BAR have significantly lower bias and smaller variance than when using EXP
      or TI, especially when the overlap in phase space between end states is small.
      For example, BAR can extract as much information from multiple fast, far-from
      equilibrium simulations as from fewer simulations near equilibrium, which EXP
      cannot. Although TI and sometimes even EXP can be somewhat more efficient in
      idealized toy problems, in the realistic atomistic situations tested in this
      paper, BAR is significantly more efficient than all other methods.

PMID- 15847517
TI  - Isotopic variation of experimental lifetimes for the lowest 1 Pi u states of N2.
AB  - Lifetimes of several (1)Pi(u) states of the three natural isotopomers of
      molecular nitrogen, (14)N(2), (14)N(15)N, and (15)N(2), are determined via
      linewidth measurements in the frequency domain. Extreme ultraviolet (XUV)+UV two
      photon ionization spectra of the b (1)Pi(u)(v=0-1,5-7) and c(3) (1)Pi(u)(v=0)
      states of (14)N(2), b (1)Pi(u)(v=0-1,5-6) and c(3) (1)Pi(u)(v=0) states of
      (14)N(15)N, and b (1)Pi(u)(v=0-7), c(3) (1)Pi(u)(v=0), and o (1)Pi(u)(v=0) states
      of (15)N(2) are recorded at ultrahigh resolution, using a narrow band tunable XUV
      laser source. Lifetimes are derived from the linewidths of single rotationally
      resolved spectral lines after deconvolution of the instrument function. The
      observed lifetimes depend on the vibrational quantum number and are found to be
      strongly isotope dependent.

PMID- 15847519
TI  - Vibrational dependence of the H2-H2 C6 dispersion coefficients.
AB  - We use the sum-over-states formalism to compute the imaginary-frequency dipole
      polarizabilities for H2, as a function of the H-H bond length, at the full
      configuration interaction level of theory using atom-centered d-aug-cc-pVQZ basis
      sets. From these polarizabilities, we obtain isotropic and anisotropic C6
      dispersion coefficients for a pair of H2 molecules as functions of the two
      molecules' bond lengths.

PMID- 15847518
TI  - Predissociation mechanism for the lowest 1 Pi u states of N2.
AB  - Separate coupled-channel Schrodinger-equation (CSE) models of the interacting
      (1)Pi(u) (b,c,o) and (3)Pi(u) (C,C(')) states of N(2) are combined, through the
      inclusion of spin-orbit interactions, to produce a five-channel CSE model of the
      N(2) predissociation. Comparison of the model calculations with an experimental
      database, consisting principally of detailed new measurements of the vibrational
      and isotopic dependence of the (1)Pi(u) linewidths and lifetimes, provides
      convincing evidence that the predissociation of the lowest (1)Pi(u) levels in
      N(2) is primarily an indirect process, involving spin-orbit coupling between the
      b (1)Pi(u)- and C (3)Pi(u)-state levels, the latter levels themselves heavily
      predissociated electrostatically by the C(') (3)Pi(u) continuum. The well-known
      large width of the b(v=3) level in (14)N(2) is caused by an accidental degeneracy
      with C(v=9). This CSE model provides the first quantitative explanation of the
      predissociation mechanism for the dipole-accessible (1)Pi(u) states of N(2), and
      is thus likely to prove useful in the construction of realistic radiative
      transfer and photochemical models for nitrogen-rich planetary atmospheres.

PMID- 15847520
TI  - Charge transport in metal oxides: a theoretical study of hematite alpha-Fe2O3.
AB  - Transport of conduction electrons and holes through the lattice of alpha
      Fe(2)O(3) (hematite) is modeled as a valence alternation of iron cations using ab
      initio electronic structure calculations and electron transfer theory.
      Experimental studies have shown that the conductivity along the (001) basal plane
      is four orders of magnitude larger than the conductivity along the [001]
      direction. In the context of the small polaron model, a cluster approach was used
      to compute quantities controlling the mobility of localized electrons and holes,
      i.e., the reorganization energy and the electronic coupling matrix element that
      enter Marcus' theory. The calculation of the electronic coupling followed the
      generalized Mulliken-Hush approach using the complete active space self
      consistent field method. Our findings demonstrate an approximately three orders
      of magnitude anisotropy in both electron and hole mobility between directions
      perpendicular and parallel to the c axis, in good accord with experimental data.
      The anisotropy arises from the slowness of both electron and hole mobilities
      across basal oxygen planes relative to that within iron bilayers between basal
      oxygen planes. Interestingly, for elementary reaction steps along either of the
      directions considered, there is only less than one order of magnitude difference
      in mobility between electrons and holes, in contrast to accepted classical
      arguments. Our findings indicate that the most important quantity underlying
      mobility differences is the electronic coupling, albeit the reorganization energy
      contributes as well. The large values computed for the electronic coupling
      suggest that charge transport reactions in hematite are adiabatic in nature. The
      electronic coupling is found to depend on both the superexchange interaction
      through the bridging oxygen atoms and the d-shell electron spin coupling within
      the Fe-Fe donor-acceptor pair, while the reorganization energy is essentially
      independent of the electron spin coupling.

PMID- 15847521
TI  - An ab initio study of the vibronic, spin-orbit, and magnetic hyperfine structure
      in the X2Pi electronic state of NCO.
AB  - In the present study we give the results of the ab initio calculations on the
      vibronic, spin-orbit, and magnetic hyperfine structure in the X (2)Pi electronic
      state of the NCO radical. The calculations of the potential surfaces and the
      electronic mean values of the hyperfine coupling constants are carried out by
      means of the density functional theory approach (B3LYP functional combined with
      an atomic orbital basis set suitable for calculations of the hyperfine
      structure). The vibronic levels, spin-orbit splitting, and the vibronic mean
      values of the components of the hyperfine tensor in the vibronic species are
      calculated using a variational method. The results of the calculations are in
      good agreement with the available experimental data.

PMID- 15847522
TI  - Vibrational energies for the X1A1, A1B1, and B1A1 states of SiH2/SiD2 and related
      transition probabilities based on global potential energy surfaces.
AB  - Transition probabilities were evaluated for the X(1)A(1)-A(1)B(1) and A(1)B(1)
      B(1)A(1) systems of SiH(2) and SiD(2) to analyze the X-->A-->B photoexcitation.
      The Franck-Condon factors (FCFs) and Einstein's B coefficients were computed by
      quantum vibrational calculations using the three-dimensional potential energy
      surfaces (PESs) of the SiH(2)(X(1)A(1),A(1)B(1),B(1)A(1)) electronic states and
      the electronic transition moments for the X-A, X-B, and A-B system. The global
      PESs were determined by the multireference configuration interaction calculations
      with the Davidson correction and the interpolant moving least-squares method
      combined with the Shepard interpolation. The obtained FCFs for the X-A and A-B
      systems exhibit that the bending mode is strongly enhanced in the excitation
      since the equilibrium bond angle greatly varies with the three states; the
      barrier to linearity is evaluated to be 21,900 cm(-1) for the X state, 6400 cm(
      1) for the A state, and 230-240 cm(-1) for the B state. The theoretical lifetimes
      for the pure bending levels of the A and B states were calculated from the
      fluorescence decay rates for the A-X, B-A, and B-X emissions.

PMID- 15847523
TI  - Valence double ionization of O2 at photon energies below and above the molecular
      double ionization threshold.
AB  - A recently developed time-of-flight photoelectron-photoelectron coincidence
      spectroscopy technique, which gives complete two-dimensional e(-)-e(-) spectra in
      single photon double ionization, is applied to molecular oxygen at photon
      energies below and above the adiabatic double ionization threshold of O(2).
      Analysis of the two-dimensional coincidence maps reveals specific indirect
      pathways for the double ionization process. Dissociative ionization paths with
      subsequent autoionization of atomic oxygen are found to be the dominant processes
      for all chosen photon energies. Spectra of the photoelectrons coincident with the
      autoionization electrons show that intermediate O(2)(+) states are involved which
      do not autoionize to molecular O(2)(2+). In particular, the ground state of
      O(2)(2+) is vibrationally resolved and shows a regular progression which can be
      well described by direct Franck-Condon transitions at an internuclear distance
      R(e)(X (1)Sigma(g)(+))=1.054 A. Quantum yields of double ionization for O(2), of
      a form discussed in this paper, are determined.

PMID- 15847524
TI  - Complete valence double photoionization of SF6.
AB  - Single photon double ionization of SF(6) has been investigated at the photon
      energies 38.71, 40.814, and 48.372 eV by using a recently developed time-of
      flight photoelectron-photoelectron coincidence spectroscopy technique which gives
      complete two-dimensional e(-)-e(-) spectra. The first complete single photon
      double ionization electron spectrum of SF(6) up to a binding energy of
      approximately 48 eV is presented and accurately interpreted with the aid of
      Green's function ADC(2) calculations. Spectra which reflect either mainly direct
      or mainly indirect (via interatomic coulombic decay of F 2s holes) double
      ionization of SF(6) are extracted from the coincidence map and discussed. A
      previous, very low value for the onset of double ionization of SF(6) is found to
      energetically coincide with a peak structure related to secondary inelastic
      scattering events.

PMID- 15847525
TI  - Ab initio dipole polarizability surfaces of water molecule: static and dynamic at
      514.5 nm.
AB  - Coupled cluster calculations with a carefully designed basis set have been
      performed to obtain both static, alpha, and dynamic at 514.5 nm, alpha(514.5 nm),
      dipole polarizability surfaces of water. We employed a medium size basis set
      (13s10p6d3f9s6p2d1f)[9s7p6d3f6s5p2d1f] consisting of 157 contracted Gaussian-type
      functions that yields values near the Hartree-Fock limit for alpha [G. Maroulis,
      J. Chem. Phys. 94, 1182 (1991)]. The alpha and alpha(514.5 nm) surfaces were able
      to reproduce all the experimentally available information about the dipole
      polarizability of water, especially the Raman spectra of gaseous H(2)O, D(2)O,
      and HDO. Vibrational averages for the dipole polarizability of water molecule are
      also reported.

PMID- 15847526
TI  - Isomerization and dissociation dynamics of HCN in a picosecond infrared laser
      field: a full-dimensional classical study.
AB  - We report a full-dimensional study of the classical dynamics of HCN-->HNC
      isomerization and of HCN rovibrational dissociation driven by a strong but
      nonionizing picosecond infrared laser field. The dynamics of the isolated
      molecule and of the molecule in liquid Ar have both been studied. Our theoretical
      and numerical results show that when all degrees of freedom are accounted for the
      field induced molecular dynamics can be totally different from what was found in
      previous studies, where the HCN molecule is restricted to a plane containing the
      external field. It is shown that as HCN is driven by an infrared laser field, the
      rotation of the H atom around the C-N bond provides an important and highly
      efficient energy absorption mechanism. In the presence of a monochromatic
      picosecond infrared laser field with an intensity of 10(13) W/cm(2), this energy
      absorption mechanism generates considerable HCN-->HNC isomerization yield or high
      rovibrational dissociation yield without molecular preorientation or
      prealignment. Our study of the field induced isomerization and dissociation
      dynamics of the same system in liquid Ar shows that the picosecond isomerization
      dynamics is insignificantly affected by the surrounding atomic liquid whereas the
      dissociation yield may be greatly suppressed in a high density liquid. The
      implications of this study for full-dimensional quantum dynamics of multiphoton
      rovibrational excitation and dissociation of triatomics are briefly discussed.

PMID- 15847527
TI  - Photophysics of aromatic molecules with low-lying pi sigma* states: fluorinated
      benzenes.
AB  - Unlike fluorinated benzenes with four or less fluorine atoms, pentafluorobenzene
      (PFB) and hexafluorobenzene (HFB) exhibit very small fluorescence yields and
      short fluorescence lifetimes. These emission anomalies suggest that the nature of
      the first excited singlet (S(1)) state may be different for the two classes of
      fluorobenzenes. Consistent with this conjecture, the time-dependent density
      functional theory calculations yield S(1) state of pi pi(*) character for
      fluorinated benzenes with four or less F atoms, and S(1) state of pi sigma(*)
      character for PFB and HFB. The pi sigma(*) character of the S(1) state of PFB and
      HFB has been confirmed by laser-induced fluorescence, which reveal the presence
      of a new electronic transition to the red of the (1)pi pi(*) (L(b))<--S(0)
      transition, which can be identified with the predicted low-energy (1)pi sigma(*)<
      -S(0) absorption. The low fluorescence yields and the short fluorescence
      lifetimes of PFB and HFB are consistent with the small radiative decay rate of
      the (1)pi sigma(*) state and efficient S(1) (pi sigma(*))-->S(0) internal
      conversion between two electronic states of very different geometries.

PMID- 15847528
TI  - Experimental study of the NaK 3 3Pi double minimum state.
AB  - We have used the Doppler-free, perturbation-facilitated optical-optical double
      resonance technique to investigate the vibrational, rotational, and hyperfine
      structure of the 3 (3)Pi double minimum state of NaK. Since this electronic state
      arises from an avoided crossing with the nearby 4 (3)Pi state, we observe
      striking patterns in the data that provide a sensitive probe of the electronic
      wave function in the various regions of the double well potential. A single-mode
      cw dye laser excites 2(A) (1)Sigma(+)(v(A),J) approximately 1(b)
      (3)Pi(Omega=0)(v(b),J) mixed singlet-triplet "window" levels from thermally
      populated rovibrational ground state levels, 1(X) (1)Sigma(+)(v(X),J+/-1).
      Further excitation by a single-mode cw Ti:sapphire laser selects various 3
      (3)Pi(0)(v(Pi),J(Pi)) rovibrational levels, which are detected by observing
      direct 3 (3)Pi(0)-->1(a) (3)Sigma(+) fluorescence in the green spectral region.
      Using the inverse perturbation approximation method, we have determined a 3
      (3)Pi(0) potential curve that reproduces the measured energies to approximately
      0.24 cm(-1). In addition, the hyperfine and spin-orbit constants, b(F) and A(v),
      have been determined for each region of the potential curve.

PMID- 15847529
TI  - A reliable ab initio potential energy surface and vibrational states for the
      ground electronic state of HgH2(X1Sigma+g).
AB  - A three-dimensional global potential energy surface for the ground (X
      (1)Sigma(+)(g))electronic state of HgH(2) is constructed from more than 13,00 ab
      initio points. These points are generated using an internally contracted
      multireference configuration interaction method with the Davidson correction and
      a large basis set. Low-lying vibrational energy levels of HgH(2), HHgD, and
      HgD(2) calculated using the Lanczos algorithm are found to be in good agreement
      with the available experimental band origins. The majority of the vibrational
      energy levels up to 9000 cm(-1) are assigned with normal mode quantum numbers.
      Our results indicate a gradual transition for the stretching vibrations from the
      normal mode regime at low energies to the local mode regime near 9000 and 8000
      cm(-1) for HgH(2) and HgD(2), respectively, as evidenced by a decreasing energy
      gap between the (0,0,n(3)) and (1,0,n(3)-1) vibrational states and bifurcation of
      the corresponding wave functions.

PMID- 15847530
TI  - Assignment in the near-threshold absorption spectrum of N2.
AB  - The absorption spectrum of N(2), just above the first ionization limit, in the
      region between 125,750 and 126,600 cm(-1), is dominated by two broad features
      which have the appearance of the towers of a "cathedral." Recently, this energy
      region has been measured by Sommavilla et al. [J. Phys. B 35, 3901 (2002)] with a
      resolution of 0.04 cm(-1) and an assignment for one of these two bands has been
      suggested. In order to discuss this assignment, we have solved the coupled
      channel Schrodinger equation with the parameters of Spelsberg and Meyer above the
      v=28 level of the b(') (1)Sigma(u)(+) state for determining the high levels of
      b('). Furthermore, we evaluate the autoionization widths and the rotational
      structure of the different possible assignments. Finally, we propose as
      assignment for the second tower of the cathedral the Rydberg state (A
      (2)Pi(u)v(+)=1)3(')d(')sigma(g) (1)Pi(u).

PMID- 15847531
TI  - Decoherence effects in reactive scattering.
AB  - Decoherence effects on quantum and classical dynamics in reactive scattering are
      examined using a Caldeira-Leggett type model. Through a study of the dynamics of
      the collinear H + H2 reaction and the transmission over simple one-dimensional
      barrier potentials, we show that decoherence leads to improved agreement between
      quantum and classical reactions and transmission probabilities, primarily by
      increasing the energy dispersion in a well-defined way. Increased potential
      nonlinearity is seen to require larger decoherence in order to attain comparable
      quantum-classical agreement.

PMID- 15847532
TI  - A theoretical study of the gas-phase chemi-ionization reaction between uranium
      and oxygen atoms.
AB  - The U+O chemi-ionization reaction has been investigated by quantum chemical
      methods. Potential-energy curves have been calculated for several electronic
      states of UO and UO(+). Comparison with the available spectroscopic and
      thermodynamic values for these species is reported and a mechanism for the chemi
      ionization reaction U+O-->UO(+)+e(-) is proposed. The U+O and Sm+O chemi
      ionization reactions are the first two metal-plus-oxidant chemi-ionization
      reactions to be studied theoretically in this way.

PMID- 15847533
TI  - Experimental detection and theoretical characterization of the H2-NHX van der
      Waals complex.
AB  - The H2-NH(X) van der Waals complex has been examined using ab initio theory and
      detected via fluorescence excitation spectroscopy of the A(3)Pi-X(3)Sigma(-)
      transition. Electronic structure calculations show that the minimum energy
      geometry corresponds to collinear H2-NH(X), with a well depth of D(e)=116 cm(-1).
      The potential-energy surface supports a secondary minimum for a T-shaped
      geometry, where the H atom of NH points towards the middle of the H2 bond (C(2v)
      point group). For this geometry the well depth is 73 cm(-1). The laser excitation
      spectra for the complex show transitions to the H2+NH(A) dissociative continuum.
      The onset of the continuum establishes a binding energy of D(0)=32+/-2 cm(-1) for
      H2-NH(X). The fluorescence from bound levels of H2-NH(A) was not detected, most
      probably due to the rapid reactive decay [H2-NH(A)-->H+NH2]. The complex appears
      to be a promising candidate for studies of the photoinitiated H2+NH abstraction
      reaction under conditions were the reactants are prealigned by the van der Waals
      forces.

PMID- 15847534
TI  - Bound-state energies in argon trimers via a variational expansion: the effects
      from many-body corrections.
AB  - In this paper we study the bound-state energies and geometries of Ar(3) for J=0,
      using the distributed Gaussian functions method that provides a configurational
      description of the different structures contributing to these states. Atom-atom
      potentials are employed and three-body long-range effects are also included in
      the computational treatment by adding to the sum of potentials the Axilrod-Teller
      triple-dipole correction for the whole rotationless energy spectrum. An estimate
      of the total number of bound states for the Ar trimer is given. With respect to
      previous calculations, limited to the lower-lying states, our results show
      slightly larger nonadditive effects and are further able to predict the full
      range of the bound spectrum. Changes on the geometries of a large part of the
      vibrationally excited states of Ar(3) when the Axilrod-Teller term is included in
      the molecular potential are found by the present study.

PMID- 15847535
TI  - Allene and pentatetraene cations as models for intramolecular charge transfer:
      vibronic coupling Hamiltonian and conical intersections.
AB  - We consider the vibronic coupling effects involving cationic states with
      degenerate components that can be represented as charge localized at either end
      of the short cumulene molecules allene and pentatetraene. Our aim is to simulate
      dynamically the charge transfer process when one component is artificially
      depopulated. We model the Jahn-Teller vibronic interaction within these states as
      well as their pseudo-Jahn-Teller coupling with some neighboring states. For the
      manifold of these states, we have calculated cross sections of the ab initio
      adiabatic potential energy surfaces along all nuclear degrees of freedom,
      including points at large distances from the equilibrium to increase the physical
      significance of our model. Ab initio calculations for the cationic states of
      allene and pentatetraene were based on the fourth-order Moller-Plesset method and
      the outer valence Green's function method. In some cases we had to go beyond this
      method and use the more involved third-order algebraic diagrammatic construction
      method to include intersections with satellite states. The parameters for a five
      state, all-mode diabatic vibronic coupling model Hamiltonian were least-square
      fitted to these potentials. The coupling parameters for the diabatic model
      Hamiltonian are such that, in comparison to allene, an enhanced preference for
      indirect charge transfer is predicted for pentatetraene.

PMID- 15847536
TI  - Single-photon spectroscopy of singlet sulfur atoms and the autoionization
      lifetime measurements of the superexcited singlet states.
AB  - Single-photon excitation spectra from the lowest singlet (1)D(2) level of sulfur
      atoms were recorded with a tunable vacuum ultraviolet (VUV) radiation source
      generated by frequency tripling in noble gases. The photolysis of CS(2) at 193 nm
      was used to produce the singlet S((1)D(2)) sulfur atoms that were then excited to
      neutral superexcited states with the tunable VUV radiation. These superexcited
      states undergo autoionization into the first ionization continuum state of
      S(+)((4)S(3/2) (o))+e(-), which is not directly accessible from the S((1)D(2))
      state via an allowed transition. The excitation spectra were recorded by
      monitoring the S(+) signal in a velocity imaging apparatus while scanning the VUV
      excitation wavelength. Three new lines were observed in the spectra which have
      not been previously reported. The full widths at half maximum (FWHM) of each of
      the observed transitions were determined by fitting the profiles of each
      absorption resonances with the Fano formula. Autoionization lifetimes tau of
      these singlet superexcited states were obtained from FWHM using the Uncertainty
      Principle. Abnormal autoionization lifetimes were found for the
      3s(2)3p(3)((2)D(o))nd((1)D(2)) and the 3s(2)3p(3)((2)D(o))ns((1)D(2)) Rydberg
      series, in which tau(5d) and tau(7s) are shorter than tau(4d) and tau(6s),
      respectively. This is contrary to the well-known scaling law of tau(n*)
      proportional, variantn(*3), which should be followed within a series unless there
      exist perturbations from other series or new channels open up to which some
      members of the series can decay. Possible perturbations from the nearby triplet
      series are suspected for causing the broadening of the 5d and 7s levels.

PMID- 15847537
TI  - Appraisal of the performance of nonhybrid density functional methods in
      characterization of the Al4C molecule.
AB  - In three recent publications it was predicted that an Al(4)C molecule is planar
      on the basis of nonhybrid density functional calculations. These conclusions
      contradict our earlier predictions that Al(4)C is tetrahedral. In order to
      resolve the controversy we probed in this paper a potential energy surface of
      Al(4)C using a large variety of theoretical methods including
      multiconfigurational methods and a variety of one-electron basis sets. We
      confirmed that the nonhybrid Becke's exchange with Perdew-Wang 1991 correlation
      functional density functional method predicts that Al(4)C has a planar structure
      in agreement with the reports of the other three groups. However, in this paper
      we have shown that high level ab initio calculations at the coupled cluster with
      singles, doubles, and noniterative triples and at the complete active space self
      consistent field followed by multireference configurational interaction levels of
      theory confirm our earlier prediction that Al(4)C is indeed tetrahedral. The
      failure of nonhybrid density functional methods to correctly characterize the
      global minimum structure of Al(4)C demonstrates that it is dangerous to rely
      solely on these density functional methods in characterization of new molecules
      and clusters, where experimental structure is not known.

PMID- 15847538
TI  - Ab initio calculations of structures and interaction energies of toluene dimers
      including CCSD(T) level electron correlation correction.
AB  - The intermolecular interaction energy of the toluene dimer has been calculated
      with the ARS-F model (a model chemistry for the evaluation of intermolecular
      interaction energy between ARomatic Systems using Feller's method), which was
      formerly called as the AIMI model III. The CCSD(T) (coupled cluster calculations
      with single and double substitutions with noniterative triple excitations)
      interaction energy at the basis set limit has been estimated from the second
      order Moller-Plesset perturbation interaction energy at the basis set limit
      obtained by Feller's method and the CCSD(T) correction term obtained using a
      medium-size basis set. The cross (C(2)) dimer has the largest (most negative)
      interaction energy (-4.08 kcal/mol). The antiparallel (C(2h)) and parallel (C(S))
      dimers (-3.77 and -3.41 kcal/mol, respectively) are slightly less stable. The
      dispersion interaction is found to be the major source of attraction in the
      toluene dimer. The dispersion interaction mainly determines the relative
      stability of the stacked three dimers. The electrostatic interaction of the
      stacked three dimers is repulsive. Although the T-shaped and slipped-parallel
      benzene dimers are nearly isoenergetic, the stacked toluene dimers are
      substantially more stable than the T-shaped toluene dimer (-2.62 kcal/mol). The
      large dispersion interaction in the stacked toluene dimers is the cause of their
      enhanced stability.

PMID- 15847539
TI  - Empirical solvent correction for multiple amide group vibrational modes.
AB  - Previously proposed solvent correction to the amide I peptide vibration was
      extended so that it can be applied to a general solvated chromophore. The
      combined molecular and quantum mechanics (MMQM) method is based on a linear
      dependence of harmonic force field and intensity tensor components of the solute
      on solvent electrostatic field. For N-methylacetamide, realistic solvent
      frequency and intensity changes as well as inhomogeneous band widths were
      obtained for amide A, I, II , and III modes. A rather anomalous basis set size
      dependence was observed for the amide A and I vibrations, when bigger basis lead
      to narrowing of spectral bands and lesser molecular sensibility to the
      environment. For a model alpha-helical peptide, a W-shape of the vibrational
      circular dichroism signal observed in deuterated solvent for the amide I band was
      reproduced correctly, unlike with previous vacuum models.

PMID- 15847540
TI  - Superdipole liquid scenario for the dielectric primary relaxation in supercooled
      polar liquids.
AB  - We propose a dynamic structure of coupled dynamic molecular strings for
      supercooled small polar molecule liquids and accordingly we obtain the
      Hamiltonian of the rotational degrees of freedom of the system. From the
      Hamiltonian, the strongly correlated supercooled polar liquid state is
      renormalized to a normal superdipole liquid state. This scenario describes the
      following main features of the primary or alpha-relaxation dynamics in
      supercooled polar liquids: (1) the average relaxation time evolves from a high
      temperature Arrhenius to a low temperature non-Arrhenius or super-Arrhenius
      behavior; (2) the relaxation function crosses over from the high temperature
      exponential to low temperature nonexponential form; and (3) the temperature
      dependence of the relaxation strength shows non-Curie features. According to the
      present model, the crossover phenomena of the first two characteristics arise
      from the transition between the superdipole gas and the superdipole liquid. The
      model predictions are quantitatively compared with the experimental results of
      glycerol, a typical glass former.

PMID- 15847541
TI  - Phase transition in single crystal Cs2Nb4O11.
AB  - We studied temperature dependence of complex capacitance, impedance, and
      polarized Raman spectra of single crystal Cs2Nb4O11. First, we observed a sharp
      lambda-shaped peak at 165 degrees C in the complex capacitance, then found
      drastic changes in the Raman spectra in the same temperature range. Utilizing the
      pseudosymmetry search of structure space group, we attributed the observed
      anomalies to a structural change from the room temperature orthorhombic Pnn2 to
      another orthorhombic Imm2. We also measured room temperature polarized Raman
      spectra in different symmetries of normal vibrations and assigned high wavenumber
      Raman bands to the internal vibrations of NbO6 octahedra and NbO4 tetrahedra.

PMID- 15847542
TI  - A theoretical study on anomalous temperature dependence of pKw of water.
AB  - pH, with its well-known value of 7 at ambient condition, is a most basic property
      of water, with wide implications in chemistry and biology. The pH value is
      determined by the tendency of autoionization of water molecules into ion pairs,
      H(+) and OH(-), and is expected to vary extensively with the water condition,
      which determines the stability of the ion pairs. When temperature rises from the
      normal to the supercritical region, the pH of water experimentally exhibits
      complex, nonmonotonic temperature dependence, that is, it first decreases from 7
      and then increases rapidly. Accurate theoretical evaluation of pH and microscopic
      understanding of this anomalous behavior have proven to be a challenging task
      because the hydration of these ions, especially for OH(-), is very difficult to
      reproduce. In the present study a molecular simulation is performed to understand
      this peculiar temperature dependence. The imbalance between the ion-water and the
      water-water molecular interaction strengths and the concomitant water density
      enhancement in the hydration shell, observed in the supercritical liquids, serve
      to put a subtle balance to produce this temperature dependence of the pH value.
      It is found that the large charge transfers from H(+) and OH(-) to the
      surrounding water molecules take place. In these transfers, not only water
      molecules in the neighboring hydration shell but also those in the outer
      hydration shell play a significant role. The coordination number of water
      molecules around OH(-) is found to be 4.5 at 300 K, which decreases slowly with
      temperature, for example, 4 at 800 K, in the present calculation.

PMID- 15847543
TI  - Levitation effect: size-dependent maximum in rotational diffusion in confined
      systems.
AB  - Molecular dynamics of a model guest tetrahedral molecule AX(4) with differing
      bond lengths l(AX) for A-X bonds have been carried out in a sphere with different
      surface roughness. The rotational-diffusion coefficient D(R) shows a maximum for
      a particular value of l(AX). We show that this corresponds to the distance at
      which the interaction of the guest with the atoms of the host is most favorable.
      Although, the intensity of the maximum decreases with increase in the roughness
      of the confining surface, it is seen that the maximum exists even for a
      reasonably high degree of roughness. The observed maximum arises from the minimum
      in the torque on the tetrahedral molecule from its interaction with the confining
      medium due to mutual cancellation of forces. Activation energy for rotation is
      seen to be also a minimum for the bond length for which D(R) is a maximum. These
      results suggest that there is a maximum in the rotational-diffusion coefficient
      when the rotating molecule is confined to a sphere of comparable size similar to
      the maximum in translational diffusion coefficient seen in porous solids (the
      levitation effect) [Yashonath and Santikary J. Phys. Chem. 98, 6368 (1994)]. On
      increase in the roughness of the sphere surface, the value of l(AX) at which the
      maximum in D(R) is seen decreases.

PMID- 15847544
TI  - Thermal properties of the metastable supersaturated vapor of the Lennard-Jones
      fluid.
AB  - p, rho, T data of the supersaturated vapor of the Lennard-Jones fluid are
      obtained by molecular dynamics simulations. The metastable state points are
      identified before a phase separation takes place. An estimation of the location
      of the spinodal is given. The results are compared to two theoretically based
      equations of state and one empirical equation of state which was parametrized
      also taking into account metastable state points. The pressure obtained by
      simulation is found to be lower than that from both theoretically based equations
      of state, which do not account for the inhomogeneous density distribution of the
      supersaturated vapor.

PMID- 15847545
TI  - Nonmonotonic composition dependence of vibrational phase relaxation rate in
      binary mixtures.
AB  - We present here isothermal-isobaric N-P-T ensemble molecular dynamics simulations
      of vibrational phase relaxation in a model system to explore the unusual features
      arising due to concentration fluctuations which are absent in one component
      systems. The model studied consider strong attractive interaction between the
      dissimilar species to discourage phase separation. The model reproduces the
      experimentally observed nonmonotonic, nearly symmetric, composition dependence of
      the dephasing rate. In addition, several other experimentally observed features,
      such as the maximum of the frequency modulation correlation time tau(c) at mole
      fraction near 0.5 and the maximum rate enhancement by a factor of about 3 above
      the pure component value, are also reproduced. The product of mean square
      frequency modulation [<Delta omega(2)(0)>] with tau(c) indicates that the present
      model is in the intermediate regime of inhomogeneous broadening. The nonmonotonic
      composition chi(A) dependence of the dephasing time tau(v) is found to be
      primarily due to the nonmonotonic chi dependence of tau(c), rather than due to a
      similar dependence in the amplitude of Delta omega(2)(0). The probability
      distribution of Delta omega shows a markedly non-Gaussian behavior at
      intermediate composition (chi(A) approximately =0.5). We have also calculated the
      composition dependence of the viscosity in order to explore the correlation
      between the composition dependence of viscosity eta(*) with that of tau(v) and
      tau(c). It is found that both the correlation time essentially follow the
      composition dependence of the viscosity. A mode coupling theory is presented to
      include the effects of composition fluctuations in binary mixture.

PMID- 15847546
TI  - Dielectric relaxation time of bulk water at 136-140 K, background loss and
      crystallization effects.
AB  - Dielectric relaxation time, tau, of ultraviscous bulk water has been determined
      by analyzing its loss tangent, tan delta, data, which had been measured on
      heating the vapor-deposited amorphous solid water and hyperquenched glassy water
      in our earlier studies. [Johari, Hallbrucker, and Mayer, J. Chem. Phys. 95, 2955
      (1991); 97, 5851 (1992)]. As for glasses and liquids generally, the measured tan
      delta of water is the sum of a frequency-independent background loss and a
      frequency-dependent relaxational loss. A two-frequency method is provided for
      determining the background loss and used for obtaining the relaxational part of
      tan delta. After considering the structural relaxation and crystal-nuclei growth
      effects, tau for water has been determined. At 136+/-1 K, it is 2.5+/-0.6 s when
      a single relaxation time is (untenably) assumed, and 42+/-14 s when a
      distribution of relaxation times, a characteristic of viscous liquids, is
      assumed, with Davidson-Cole distribution parameter of 0.75. Structural relaxation
      time of approximately 70 s for water at 136 K, which was originally estimated
      from the DSC endotherm [Johari, Hallbrucker, and Mayer, Nature (London) 330, 552
      (1987)], has been revised to approximately 33 s. Temperature dependence of tau
      could not be determined because ultraviscous water crystallizes too rapidly to
      cubic ice containing stacking faults and intergranular water. The study
      demonstrates that water is a liquid over the 136-155 K range, thus removing the
      basis for a recent contention on its state.

PMID- 15847547
TI  - Density functional study of the interaction of chlorine atom with small neutral
      and charged silver clusters.
AB  - Chlorine adsorption on small neutral, anionic, and cationic silver clusters Ag(n)
      (n=2-7) has been studied using the PW91PW91 density functional method. It was
      found that the adsorption of chlorine on the lowest-energy bare clusters does not
      always produce the lowest-energy complexes. In addition, the binding of chlorine
      can greatly change the geometries of the silver clusters in some cases. Among
      various possible adsorption sites, bridge site is energetically preferred for the
      neutral Ag(n) while top site is energetically more preferred for the anionic
      Ag(n) with n< or =6. For cationic clusters, adsorptions on bridge and face sites
      have similar binding energies, which are much larger than those on top sites.
      Natural bond orbital analyses show that irrespective of charge state, electrons
      always transfer from silver atoms to adsorbate and silver acts like alkali metals
      in the interaction with chlorine atom. Significant odd-even alternation patterns
      in the properties of the complexes have been observed: Even-electron clusters
      often have higher ionization energies, lower electron affinities, and higher
      dissociation energies than their odd-electron neighbors. It was also found that
      chlorine atoms bind more strongly with odd-electron bare clusters than with even
      electron bare clusters. These patterns reveal that even-electron clusters are
      more stable than odd-electron clusters.

PMID- 15847548
TI  - Counterion condensation and release in micellar solutions.
AB  - Counterion condensation and release in micellar solutions are investigated by
      direct measurement of counterion concentration with ion-selective electrode.
      Monte Carlo simulations based on the cell model are also performed to analyze the
      experimental results. The degree of counterion condensation is indicated by the
      concentration ratio of counterions in the bulk to the total ionic surfactant
      added, alpha< or =1. The ionic surfactant is completely dissociated below the
      critical micelle concentration (cmc). However, as cmc is exceeded, the free
      counterion ratio alpha declines with increasing the surfactant concentration and
      approaches an asymptotic value owing to counterion condensation to the surface of
      the highly charged micelles. Micelle formation leads to much stronger
      electrostatic attraction between the counterion and the highly charged sphere in
      comparison to the attraction of single surfactant ion with its counterion. A
      simple model is developed to obtain the true degree of ionization, which agrees
      with our Monte Carlo results. Upon addition of neutral polymer or monovalent
      salts, some of the surfactant counterions are released to the bulk. The former is
      due to the decrease of the intrinsic charge (smaller aggregation number) and the
      degree of ionization is increased. The latter is attributed to competitive
      counterion condensation, which follows the Hefmeister series. This consequence
      indicates that the specific ion effect plays an important role next to the
      electrostatic attraction.

PMID- 15847549
TI  - Current and noise in a model of an alternating current scanning tunneling
      microscope molecule-metal junction.
AB  - The transport properties of a simple model for a finite level structure (a
      molecule or a dot) connected to metal electrodes in an alternating current
      scanning tunneling microscope (ac-STM) configuration is studied. The finite level
      structure is assumed to have strong binding properties with the metallic
      substrate, and the bias between the STM tip and the hybrid metal-molecule
      interface has both an ac and a dc component. The finite frequency current
      response and the zero-frequency photoassisted shot noise are computed using the
      Keldysh technique, and examples for a single-site molecule (a quantum dot) and
      for a two-site molecule are examined. The model may be useful for the
      interpretation of recent experiments using an ac-STM for the study of both
      conducting and insulating surfaces, where the third harmonic component of the
      current is measured. The zero-frequency photoassisted shot noise serves as a
      useful diagnosis for analyzing the energy level structure of the molecule. The
      present work motivates the need for further analysis of current fluctuations in
      electronic molecular transport.

PMID- 15847550
TI  - Hole localization in [AlO4]0 defects in silica materials.
AB  - First-principles calculations based on cluster models have been performed to
      investigate the ground state and the optically excited states of the [AlO(4)](0)
      hole in alpha-quartz and in the siliceous zeolite ZSM-5. The structure and
      spectroscopic properties of this defect have been studied using the recently
      developed Becke88-Becke95 one-parameter model for kinetics (BB1K) functional of
      Zhao et al., [J. Phys. Chem. A 108, 2715 (2004)]. Our results show that the BB1K
      method is significantly more reliable and more accurate than the standard density
      functional theory (DFT) functionals at reproducing the localized spin density on
      one oxygen atom and the hyperfine coupling constants associated with the hole.
      Furthermore, we find that the BB1K results are in close agreement with
      experiments, and with the self-interaction-free unrestricted Hartree-Fock (UHF)
      and unrestricted second-order Moller-Plesset perturbation theory (UMP2)
      calculations. For the first time, we present results of the ground-state
      paramagnetic properties of the Al defect in ZSM-5. Similar to the theoretical
      work for defective alpha-quartz, we find that the BB1K, UHF, UHFLee-Yang-Parr,
      and UMP2 calculations show a localized hole on one oxygen neighboring the Al,
      while even the best to date thermochemically derived hybrid generalized gradient
      approximation density-functional, B97-2, predicts a different model where the
      hole is distributed over two oxygen. We have further considered the optical
      transitions of the [AlO(4)](0) center in alpha-quartz and ZSM-5. In both systems,
      our BB1K time-dependent density-functional theory (TDDFT) and configuration
      interaction singles (CIS) calculations predict that the most likely transition
      involves electron transfer from the hole-bearing oxygen to other neighboring
      oxygen ions. This reinforces the experimental conclusions obtained for defective
      alpha-quartz. Notably, the two lowest, most dominant excitation energies
      calculated by BB1K-TDDFT (1.99 and 3.03 eV) show excellent agreement with
      experiment (1.96 and 2.85 eV [B. K. Meyer, J.M. Spaeth, and J.A. Weil, J. Phys.
      C: Solid State Phys. 17, L31 (1987)]) clearly outperforming the CIS method and
      other DFT calculations available in the literature.

PMID- 15847551
TI  - Kinetic oscillations in the NO+CO reaction on the Pt(100) surface: an alternative
      reaction mechanism.
AB  - Kinetic oscillations in the catalytic reduction of NO by CO on a reconstructing
      Pt(100) surface are simulated by using a dynamic Monte Carlo method. The
      simulation is based on the HS model and takes into account an alternative
      reaction mechanism arising from recent experimental findings for the catalytic
      reduction of No on Rh(111), which replaces the classical N+N recombination step
      by the formation of a (N-NO)(*) intermediary species for the production of
      molecular nitrogen. A synchronized mechanism and spatiotemporal patterns are
      observed during the oscillations. Oscillations are analyzed in terms of the
      controlling parameters involved in the reaction mechanism. Different values of
      these parameters lead to sustained, attenuated, and modulated oscillations.

PMID- 15847552
TI  - Molecular modeling of freezing of simple fluids confined within carbon nanotubes.
AB  - We report Monte Carlo simulation results for freezing of Lennard-Jones carbon
      tetrachloride confined within model multiwalled carbon nanotubes of different
      diameters. The structure and thermodynamic stability of the confined phases, as
      well as the transition temperatures, were determined from parallel tempering
      grand canonical Monte Carlo simulations and free-energy calculations. The
      simulations show that the adsorbate forms concentric molecular layers that
      solidify into defective quasi-two-dimensional hexagonal crystals. Freezing in
      such concentric layers occurs via intermediate phases that show remnants of
      hexatic behavior, similar to the freezing mechanism observed for slit pores in
      previous works. The adsorbate molecules in the inner regions of the pore also
      exhibit changes in their properties upon reduction of temperature. The structural
      changes in the different regions of adsorbate occur at temperatures above or
      below the bulk freezing point, depending on pore diameter and distance of the
      adsorbate molecules from the pore wall. The simulations show evidence of a rich
      phase behavior in confinement; a number of phases, some of them inhomogeneous,
      were observed for the pore sizes considered. The multiple transition temperatures
      obtained from the simulations were found to be in good agreement with recent
      dielectric relaxation spectroscopy experiments for CCl(4) confined within
      multiwalled carbon nanotubes.

PMID- 15847553
TI  - Phase behavior of the restricted primitive model of ionic fluids with association
      in slitlike pores. Density-functional approach.
AB  - We present results of investigations of condensation of restricted primitive
      model of electrolyte solutions with association between oppositely charged ions
      confined to slitlike pores. The associative interaction leads to the formation of
      ionic pairs. It is accounted for by incorporating the first-order thermodynamic
      perturbation theory into the free energy functional. In order to elucidate the
      role of association, the phase diagrams are compared with those obtained by us
      recently [O. Pizio et al., J. Chem. Phys. 121, 11957 (2004)] for the restricted
      primitive model. The inclusion of the association into the theory leads to
      lowering the critical temperature for the fluid confined to pores with uncharged
      and with charged walls. We have observed that the average fraction of bonded ions
      is high along the coexistence envelope.

PMID- 15847554
TI  - Correlations between adhesion hysteresis and friction at molecular scales.
AB  - Correlations between adhesion hysteresis and local friction are theoretically and
      experimentally investigated. The model is based on the classical theory of
      adhesional friction, contact mechanics, capillary hysteresis, and nanoscale
      roughness. Adhesion hysteresis was found to scale with friction through the
      scaling factor containing a varying ratio of adhesion energy over the reduced
      Young's modulus. Capillary forces can offset the relationship between adhesion
      hysteresis and friction. Measurements on a wide range of engineering samples with
      varying adhesive and elastic properties confirm the model. Adhesion hysteresis is
      investigated under controlled, low humidity atmosphere via ultrasonic force
      microscopy. Friction is measured by the friction force microscopy.

PMID- 15847555
TI  - Reactions and clustering of water with silica surface.
AB  - The interaction between silica surface and water is an important topic in
      geophysics and materials science, yet little is known about the reaction process.
      In this study we use first-principles molecular dynamics to simulate the
      hydrolysis process of silica surface using large cluster models. We find that a
      single water molecule is stable near the surface but can easily dissociate at
      three-coordinated silicon atom defect sites in the presence of other water
      molecules. These extra molecules provide a mechanism for hydrogen transfer from
      the original water molecule, hence catalyzing the reaction. The two-coordinated
      silicon atom is inert to the water molecule, and water clusters up to pentamer
      could be stably adsorbed at this site at room temperature.

PMID- 15847556
TI  - Structural and kinetic effects on a simple catalytic reaction: oxygen reduction
      on Ni(110).
AB  - Oxygen hydrogenation at 100 K by gas phase atomic hydrogen on Ni(110) has been
      studied under ultrahigh vacuum conditions by temperature programmed desorption
      (TPD) and x-ray photoelectron spectroscopy (XPS). Formation of adsorbed water and
      hydroxyl species was observed and characterized. The coverage of the reaction
      products was monitored as a function of both temperature and initial oxygen
      precoverage. On the contrary, when high coverage oxygen overlayers were exposed
      to gas phase molecular hydrogen, no hydrogenation reaction took place. The
      results are compared to the inverse process, exposing the hydrogen covered
      surface to molecular oxygen. In this case, at 100 K, simple Langmuir-Hinshelwood
      modeling yields an initial sticking coefficient for oxygen adsorption equal to
      0.26, considerably lower than for the clean surface. Moreover, formation of
      hydroxyl groups is found to be twice as fast as the final hydrogenation of OH
      groups to water. Assuming a preexponential factor of 10(13) s(-1), an activation
      barrier of 6.7 kcal/mol is obtained for OH formation, thus confirming the high
      hydrogenating activity of nickel with respect to other transition metals, for
      which higher activation energies are reported. However, oxygen is hardly removed
      by hydrogen on nickel: this is explained on the basis of the strong Ni-O chemical
      bond. The hydrogen residual coverage is well described including a contribution
      from the adsorption-induced H desorption process which takes place during the
      oxygen uptake and which is clearly visible from the TPD data.

PMID- 15847557
TI  - Comparison of classical and quantum dynamics for collinear cluster scattering.
AB  - The collinear dynamics of a cluster of four particles colliding with a fixed
      particle representing a surface is investigated using a four-dimensional wave
      packet approach. The properties of the system are chosen to resemble a water
      cluster interacting with graphite, but a deeper surface-particle potential is
      also considered causing significant dissociation of the cluster. Having four
      different product arrangement channels the system is quantum mechanically
      demanding but still manageable. The dynamical richness makes it a suitable
      benchmark system for evaluation of classical and quantum/classical schemes. The
      average energy transferred to the cluster and the three dissociation
      probabilities are presented as function of the initial state of the cluster. In
      addition to wave packet data, results obtained using quasiclassical as well as
      Wigner sampled classical trajectories are presented. The main conclusion is that
      classical mechanics can describe the dynamics of the system in a very
      satisfactory way. Including zero-point energy in the classical simulations is
      particularly important for a good description of dissociation but less important
      for energy transfer.

PMID- 15847558
TI  - Local dynamic mechanical properties in model free-standing polymer thin films.
AB  - High-frequency sinusoidal oscillations of a coarse-grained polymer model are used
      to calculate the local dynamic mechanical properties (DMPs) of free-standing
      polymer thin films. The storage modulus G(') and loss modulus G(") are examined
      as a function of position normal to the free surfaces. It is found that
      mechanically soft layers arise near the free surfaces of glassy thin films, and
      that their thickness becomes comparable to the entire film thickness as the
      temperature approaches the glass transition T(g). As a result, the overall
      stiffness of glassy thin films decreases with film thickness. It is also shown
      that two regions coexist in thin films just at the bulk T(g); a melt-like region
      (G(')<G(")) near the free surfaces and a glass-like region (G(')>G(")) in the
      middle of the film. Our findings on the existence of a heterogeneous distribution
      of DMPs in free-standing polymer thin films provide insights into recent
      experimental measurements of the mechanical properties of glassy polymer thin
      films.

PMID- 15847559
TI  - Crystallization in charged two-component suspensions.
AB  - We report on the crystallization of colloidal crystals comprising of charged
      particles with different size ratio dispersed in thoroughly deionized water.
      Single components were characterized carefully and their nucleation behavior was
      investigated before the preparation of mixtures. Mixtures investigated at
      constant particle number densities showed body centred cubic structure,
      conductivity, and shear moduli comply with the assumption of a randomly
      substituted crystal. Most importantly, for the first time we obtain the
      dependence of the nucleation rate densities in dependence on the composition and
      (for one fixed composition) the particle number density. The process of
      nucleation in random substitutional crystals is found to be similar to the one
      component case.

PMID- 15847560
TI  - A dissipative particle dynamics description of liquid-crystalline phases. I.
      Methodology and applications.
AB  - Simulations of nematic and smectic mesophases based on a dissipative particle
      dynamics approach are discussed. Mesogenic units are built in the form of
      standard semirigid bead-spring chains. It is shown that nematic phases can be
      formed for chains containing at least eight beads, provided that the conservative
      soft-repulsive potential between nonconnected beads is sufficiently strong.
      Smectic phases are observed only by modifying the repulsive interaction between
      the main-chain and terminal beads. The simulations indicate that the smectic
      nematic and smectic-isotropic phase transitions take place through the buckling
      of the smectic layering in the system.

PMID- 15847561
TI  - A novel method for static equation-of state-development: equation of state of a
      cross-linked poly(dimethylsiloxane) (PDMS) network to 10 GPa.
AB  - Pressure-volume-temperature (PVT) equation-of-state (EOS) information for
      polymers and polymeric composites is valuable for predicting their response to
      extreme conditions. An obstacle in determining equations of state for polymeric
      materials is the lack of a simple, static experimental method for acquiring PVT
      data for solid networks and liquids at pressures greater than several kilobars.
      Here, we report a novel approach in determining static EOS for polymers using
      high-pressure diamond-anvil cells coupled with optical microscopy and image
      analysis. Results are presented for a cross-linked poly(dimethylsiloxane)
      polymer, Sylgard 184. Static isothermal results were fitted to empirical and
      semiempirical equations of state, including the Tait, Birch-Murnaghan, and Vinet
      forms. Static PV data were also converted to pseudoshock velocity-pseudoparticle
      velocity (U(s)-u(p)) for comparison to dynamic Hugoniot data. A linear Rankine
      Hugoniot fit U(s)=s(T)u(p)+c(T) gives c(T)=1.572 km/s and s(T)=1.703. s(T) is
      related to the pressure derivative of the bulk modulus B(0) (') by s(T)=(B(0)
      (')+1)/4 and B(0) (')=5.8. A comparison of the static and shock data is given,
      along with an estimate of the Gruneisen parameter, and a discussion of the free
      volume content in the polymer network, and limitations of this novel method.

PMID- 15847562
TI  - Scaling behavior of a brush-homopolymer interface in the limit of high grafting
      density.
AB  - The interface between a polymer brush and a chemically equivalent homopolymer is
      examined using self-consistent field theory (SCFT). Focusing on ultrahigh
      grafting densities, we extract how the properties scale with the brush thickness,
      L, and compare with predictions based on strong-stretching theory (SST). Although
      the scaling exponents are consistent, the overall agreement is poor. We attribute
      this to the inaccurate way the SST-based calculation treats chain fluctuations at
      the extremity of the brush. This accounts for a previous disagreement between
      SCFT and SST in regards to autophobic dewetting, and brings into question a
      number of other SST predictions. Our conclusion is that SST requires a more
      sophisticated treatment of finite-stretching corrections, along the lines of that
      proposed by Likhtman and Semenov [Europhys. Lett. 51, 307 (2000)].

PMID- 15847563
TI  - Dynamics of deuterated polystyrene-protonated butadiene diblock copolymer
      micelles by neutron spin echo.
AB  - We report on neutron spin-echo (NSE) measurements on deuterated styrene
      protonated butadiene diblock copolymer micelles in deuterated n-decane to
      investigate the dynamics of butadiene blocks in the corona. Before the NSE
      measurements, we performed small-angle neutron-scattering (SANS) measurements on
      the micelles to evaluate the structure to give a basis for the discussion of the
      dynamics. In the SANS study, we have estimated the form factor P(Q) in terms of a
      hard-core-shell model from the direct evaluation without curve-fitting procedure
      while a more flexible core-shell model with the structure factor S(Q) gives a
      better fit to the observed data. The observed normalized intermediate scattering
      function I(Q,t)/I(Q,0) by NSE does not show the collective motions corresponding
      to the so-called breathing mode but rather single chain motion (Zimm modes) for
      both the 2 and 20 wt % micelle solutions. The Zimm decay rate Gamma(z) in the
      micelle solution is slow compared with that in the homopolymer solution. This
      slowing down is assigned to the effective high concentration in the corona. The
      differences in Gamma(z) between concentrated solutions and the 20% micellar
      solution are attributed to end-tethering effect of the corona chains on the core
      surface. The possible reasons why the breathing mode was not observed in the
      present micelle system are discussed on the basis of chain density in the corona.

PMID- 15847564
TI  - Generation of frustrated liquid crystal phases by mixing an achiral nematic
      smectic-C mesogen with an antiferroelectric chiral smectic liquid crystal.
AB  - By mixing the achiral liquid crystal HOAB, exhibiting a nematic (N)-smectic-C
      (SmC) mesophase sequence, with the chiral antiferroelectric liquid crystal (AFLC)
      (S,S)-M7BBM7, forming the antiferroelectric SmC(a)(*) phase, at least seven
      different mesophases have been induced which neither component forms on its own:
      a twist-grain-boundary (TGB(*)) phase, two or three blue phases, the untilted
      SmA(*) phase, as well as all three chiral smectic-C-type "subphases,"
      SmC(alpha)(*), SmC(beta)(*), and SmC(gamma)(*). The nature of the induced phases
      and the transitions between them were determined by means of optical and electro
      optical investigations, dielectric spectroscopy, and differential scanning
      calorimetry. The induced phases can to a large extent be understood as a result
      of frustration, TGB(*) at the border between nematic and smectic, the subphases
      between syn and anticlinic tilted smectic organization. X ray scattering
      experiments reveal that the smectic layer spacing as well as the degree of
      smectic order is relatively constant in the whole mixture composition range in
      which AFLC behavior prevails, whereas both these parameters rapidly decrease as
      the amount of HOAB is increased to such an extent that no other smectic-C-type
      phase than SmC/SmC(*) exists. By tailoring the composition we are able to produce
      liquid crystal mixtures exhibiting unusual phase sequences, e.g., with a direct
      isotropic-SmC(a)(*) transition or a temperature range of the SmC(beta)(*)
      subphase of about 50 K.

PMID- 15847565
TI  - A lattice Boltzmann algorithm for electro-osmotic flows in microfluidic devices.
AB  - In this paper, a finite-difference-based lattice Boltzmann (LB) algorithm is
      proposed to simulate electro-osmotic flows (EOF) with the effect of Joule
      heating. This new algorithm enables a nonuniform mesh to be adapted, which is
      desirable for handling the extremely thin electrical double layer in EOF. The LB
      algorithm has been validated by simulating a problem with an available analytical
      solution and it is found that the numerical results predicted by the algorithm
      are in good agreement with the analytical solution. The LB algorithm is also
      applied to modeling a mixed electro-osmotic/pressure driven flow in a channel.
      The numerical results show that Joule heating plays an important role in EOF.

PMID- 15847566
TI  - Cavity resonators of metal-coated dielectric nanorods.
AB  - Metallic nanoparticles bridge the length scale between atoms and crystals,
      exhibiting mesoscopic properties unique to their size. Thus, they have generated
      much interest for their potential applications as chemical or biological sensors
      and particularly as waveguides for light in nanoscale structures. [Y. W. C. Cao,
      R. C. Jin, and C. A. Mirkin, Science 297, 1536 (2002); H. J. Lezec et al.,
      Science 297, 820 (2002); S. A. Maier, P. G. Kik, and H. A. Atwater, Appl. Phys.
      Lett. 81, 1714 (2002); J. M. Oliva and S. K. Gray, Chem. Phys. Lett. 379, 325
      (2003)]. One important direction of research into the properties of individual
      metal nanoparticles involves the controlled variation of their geometry, which
      can yield new and tunable optical properties that simple spherical configurations
      do not possess. [T. S. Ahmadi, Z. L. Wang, T. C. Green, A. Henglein, and M. A. Ei
      Sayed, Science 272, 1924 (1996)]. A prime example of this is the core-shell
      nanostructure that has a central material surrounded by differing cladding layer.

PMID- 15847568
TI  - Optical single-channel recording: imaging Ca2+ flux through individual ion
      channels with high temporal and spatial resolution.
AB  - Developments in imaging technology now enable visualization of the functioning of
      individual ion channels in living cells: something previously possible only by
      the electrophysiological patch-clamp technique. We review techniques that track
      channel gating via changes in intracellular [Ca2+] resulting from openings of
      Ca(2+)-permeable channels. Spatial and temporal resolution are optimized by
      monitoring Ca2+ close to the channel mouth, and we describe the use of two
      imaging modalities: confocal laser scan microscopy (linescan CLSM) and total
      internal reflection fluorescence microscopy (TIRFM). Both currently achieve a
      kinetic resolution of <10 ms, provide a simultaneous and independent readout from
      many channels, and enable their locations to be mapped with submicrometer
      resolution. TIRFM provides 2-D images from a very thin (approximately 100 nm)
      optical section, but it is restricted to channels in the plasma membrane of cells
      adhering close to a cover glass. In contrast, CLSM can image channels in
      intracellular membranes but, to achieve good temporal resolution, has been
      utilized only in a linescan mode with limited spatial information. We anticipate
      that imaging techniques will develop as a useful adjunct to patch-clamping for
      single-channel studies, with capabilities including simultaneous readout from
      multiple channels, high-resolution mapping of channel location, and mobility that
      is inaccessible by electrophysiological means. Optical single-channel recording
      is applicable to diverse voltage- and ligand-gated Ca(2+)-permeable channels and
      has potential for high-throughput functional analysis.

PMID- 15847569
TI  - Optical release of caged glutamate for stimulation of neurons in the in vitro
      slice preparation.
AB  - Optical stimulation techniques prove useful to map functional inputs in the in
      vitro brain slice preparation: Glutamate released by a focused beam of UV light
      induces action potentials, which can be detected in postsynaptic neurons. The
      direct activation effect is influenced by factors such as compound concentration,
      focus depth, light absorption in the tissue, and sensitivity of different
      neuronal domains. We analyze information derived from direct stimulation
      experiments in slices from rat barrel cortex and construct a computational model
      of a layer V pyramidal neuron that reproduces the experimental findings. The
      model predictions concerning the influence of focus depth on input maps and
      action potential generation are investigated further in subsequent experiments
      where the focus depth of a high-numerical-aperture lens is systematically varied.
      With our setup flashes from a xenon light source can activate neuronal
      compartments to a depth of 200 mum below the surface of the slice. The response
      amplitude is influenced both by tissue depth and focus plane. Specific
      somatodendritic structures can be targeted as the probability of action potential
      induction falls off exponentially with distance. Somata and primary apical
      dendrites are most sensitive to uncaged glutamate with locally increased
      sensitivity on proximal apical dendrites. We conclude that optical stimulation
      can be targeted with high precision.

PMID- 15847570
TI  - Cortical spreading depression produces long-term disruption of activity-related
      changes in cerebral blood volume and neurovascular coupling.
AB  - Cortical spreading depression (CSD) is a pronounced depolarization of neurons and
      glia that spreads slowly across the cortex followed by a period of depressed
      electrophysiological activity. The vascular changes associated with CSD are a
      large transient increase in blood flow followed by a prolonged decrease lasting
      greater than 1 h. Currently, the profile of functional vascular activity during
      this hypovolemic period has not been well characterized. Perfusion-based imaging
      techniques such as functional magnetic resonance imaging (fMRI) assume a tight
      coupling between changes in neuronal and vascular activity. Under normal
      conditions, these variables are well correlated. Characterizing the effect of CSD
      on this relationship is an important step to understand the impact acute
      pathophysiological events may have on neurovascular coupling. We examine the
      effect of CSD on functional changes in cerebral blood volume (CBV) evoked by
      cortical electrophysiological activity for 1 h following CSD induction. CBV
      signal amplitude, duration, and time to peak show little recovery at 60 min post
      induction. Analysis of spontaneous vasomotor activity suggests a decrease in
      vascular reactivity may play a significant role in the disruption of normal
      functional CBV responses. Electrophysiological activity is also attenuated but to
      a lesser degree. CBV and evoked potentials are not well correlated following CSD,
      suggesting a breakdown of the neurovascular coupling relationship.

PMID- 15847571
TI  - Interpretation of principal components of the reflectance spectra obtained from
      multispectral images of exposed pig brain.
AB  - The spatial variation in reflectance such as the blood-vessel pattern can be
      observed in the image of cerebral cortex. This spatial variation is mainly caused
      by the difference in concentrations of oxy- and deoxyhemoglobin in the tissue. We
      analyze the reflectance spectra obtained from multispectral images of pig cortex
      by principal component analysis to extract information that relates to
      physiological parameters such as the concentrations of oxy- and deoxyhemoglobin
      and physical parameters such as mean optical path length. The light propagation
      in a model of exposed pig cortex is predicted by Monte Carlo simulation to
      estimate the interpretation of physiological and physical meanings of the
      principal components. The spatial variance of reflectance spectra of the pig
      cortex can be approximately described by the first principal component. The first
      principal component reflects the spectrum of hemoglobin in the cortical tissue
      multiplied by the mean optical path length. These results imply that the
      wavelength dependence of mean optical path length can be experimentally estimated
      from the first principal component of the reflectance spectra obtained from
      multispectral image of cortical tissue.

PMID- 15847572
TI  - Imaging ex vivo healthy and pathological human brain tissue with ultra-high
      resolution optical coherence tomography.
AB  - The ability of ultra-high-resolution optical coherence tomography (UHR OCT) to
      discriminate between healthy and pathological human brain tissue is examined by
      imaging ex vivo tissue morphology of various brain biopsies. Micrometer-scale OCT
      resolution (0.9x2 microm, axialxlateral) is achieved in biological tissue by
      interfacing a state-of-the-art Ti:Al2O3 laser (lambda(c)=800 nm, delta lambda=260
      nm, and P(out)=120 mW exfiber) to a free-space OCT system utilizing dynamic
      focusing. UHR OCT images are acquired from both healthy brain tissue and various
      types of brain tumors including fibrous, athypical, and transitional meningioma
      and ganglioglioma. A comparison of the tomograms with standard hematoxylin and
      eosin (H&E) stained histological sections of the imaged biopsies demonstrates the
      ability of UHR OCT to visualize and identify morphological features such as
      microcalcifications (>20 microm), enlarged nuclei of tumor cells (approximately 8
      to 15 microm), small cysts, and blood vessels, which are characteristic of
      neuropathologies and normally absent in healthy brain tissue.

PMID- 15847573
TI  - Development of an optical approach for noninvasive imaging of Alzheimer's disease
      pathology.
AB  - Alzheimer's disease (AD) is characterized by the presence of aggregates of the
      amyloid-beta (A beta) peptide in the brain. These aggregates manifest themselves
      as senile plaques and cerebrovascular amyloid angiopathy (CAA). While traditional
      histochemical approaches can easily identify these deposits in postmortem tissue,
      only recently have specific ligands been developed to target A beta in living
      patients using positron emission tomography (PET). Successful detection of A beta
      pathology in patients will enable definitive preclinical diagnosis of AD, and
      enable quantitative evaluation of the efficacy of anti-A beta therapeutics
      developed to treat the disease. PET scanning, however, has several disadvantages
      including high cost, low availability, and the requirement for radioactive
      tracers. We describe recent progress in the development of techniques for imaging
      A beta deposits noninvasively using optical approaches. Successful development of
      an optical detection platform would enable inexpensive, accessible,
      nonradioactive detection of the A beta deposits found in AD.

PMID- 15847574
TI  - Measurement of brain activity by near-infrared light.
AB  - We review our most recent results on near-IR studies of human brain activity,
      which have been evolving in two directions: detection of neuronal signals and
      measurements of functional hemodynamics. We discuss results obtained so far,
      describing in detail the techniques we developed for detecting neuronal activity,
      and presenting results of a study that, as we believe, confirms the feasibility
      of neuronal signal detection. We review our results on near-IR measurements of
      cerebral hemodynamics, which are performed simultaneously with functional
      magnetic resonance imaging (MRI) These results confirm the cerebral origin of
      hemodynamic signals measured by optical techniques on the surface of the head. We
      also show how near-IR methods can be used to study the underlying physiology of
      functional MRI signals.

PMID- 15847575
TI  - Near-infrared spectroscopy for functional studies of brain activity in human
      infants: promise, prospects, and challenges.
AB  - A recent workshop brought together a mix of researchers with expertise in optical
      physics, cerebral hemodynamics, cognitive neuroscience, and developmental
      psychology to review the potential utility of near-IR spectroscopy (NIRS) for
      studies of brain activity underlying cognitive processing in human infants. We
      summarize the key findings that emerged from this workshop and outline the pros
      and cons of NIRS for studying the brain correlates of perceptual, cognitive, and
      language development in human infants.

PMID- 15847576
TI  - Using near-infrared spectroscopy to assess neural activation during object
      processing in infants.
AB  - The capacity to represent the world in terms of numerically distinct objects
      (i.e., object individuation) is a milestone in early cognitive development and
      forms the foundation for more complex thought and behavior. Over the past 10 to
      15 yr, infant researchers have expended a great deal of effort to identify the
      origins and development of this capacity. In contrast, relatively little is known
      about the neural mechanisms that underlie the ability to individuate objects, in
      large part because there are a limited number of noninvasive techniques available
      to measure brain functioning in human infants. Recent research suggests that near
      IR spectroscopy (NIRS), an optical imaging technique that uses relative changes
      in total hemoglobin concentration and oxygenation as an indicator of neural
      activation, may be a viable procedure for assessing the relation between object
      processing and brain function in human infants. We examine the extent to which
      increased neural activation, as measured by NIRS, could be observed in two neural
      areas known to be involved in object processing, the primary visual cortex and
      the inferior temporal cortex, during an object processing task. Infants aged 6.5
      months are presented with a visual event in which two featurally distinct objects
      emerge successively to opposite sides of an occluder and neuroimaging data are
      collected. As predicted, increased neural activation is observed in both the
      primary visual and inferior cortex during the visual event, suggesting that these
      neural areas support object processing in the young infant. The outcome has
      important implications for research in cognitive development, developmental
      neuroscience, and optical imaging.

PMID- 15847578
TI  - Bilateral prefrontal cortex oxygenation responses to a verbal fluency task: a
      multichannel time-resolved near-infrared topography study.
AB  - The letter-fluency task-induced response over the prefrontal cortex is
      investigated bilaterally on eight subjects using a recently developed compact,
      eight-channel, time-resolved, near-IR system. The cross-subject mean values of
      prefrontal cortex oxygen saturation (SO2) were 68.8+/-3.2% (right) and 71.0+/
      3.6% (left), and of total hemoglobin concentration (tHb) were 69.6+/-9.6 microM
      (right) and 69.5+/-9.9 microM (left). The typical cortical activation response to
      the cognitive task [characterized by an increase in oxyhemoglobin (O2Hb) with a
      concurrent decrease in deoxyhemoglobin (HHb)] at each measurement point is
      observed in only four subjects. In this subset, the amplitude of the O2Hb
      increase and HHb decrease is uniform over each prefrontal cortex area and
      comparable between the two hemispheres. These findings agree with previous
      studies using continuous wave functional near-IR spectroscopy and functional
      magnetic resonance imaging, therefore demonstrating the potential of a time
      resolved spectroscopy approach. In addition, a significant increase in SO2 levels
      was observed in the right (1.1+/-0.5%) compared to left side of the prefrontal
      cortex (0.9+/-0.5%) (P=0.005). A different pattern of cortical activation
      (characterized by the lack of HHb decrease or even increased HHb) was observed in
      the remaining subjects.

PMID- 15847577
TI  - Near-infrared frequency-domain optical spectroscopy and magnetic resonance
      imaging: a combined approach to studying cerebral maturation in neonatal rabbits.
AB  - The neonatal rabbit brain shows prolonged postnatal development both structurally
      and physiologically. We use noninvasive near-IR frequency-domain optical
      spectroscopy (NIRS) and magnetic resonance imaging (MRI) to follow early
      developmental changes in cerebral oxygenation and anatomy, respectively. Four
      groups of animals are measured: NIRS in normals, MRI in normals, and both NIRS
      and MRI with hypoxia-ischemia (HI) (diffusion MRI staging). NIRS and/or MRI are
      performed from P3 (postnatal day=P) up to P76. NIRS is performed on awake animals
      with a frequency-domain tissue photometer. Absolute values of oxyhemoglobin
      concentration ([HbO2]), deoxyhemoglobin concentration ([HbR]), total hemoglobin
      concentration (HbT), and hemoglobin saturation (StO2) are calculated. The brains
      of all animals appeared to be maturing as shown in the diffusion tensor MRI. Mean
      optical coefficients (reduced scattering) remained unchanged in all animals
      throughout. StO2 increased in all animals (40% at P9 to 65% at P43) and there are
      no differences between normal, HI controls, and HI brains. The measured increase
      in StO2 is in agreement with the reported increase in blood flow during the first
      2 months of life in rabbits. HbT, which reflects blood volume, peaked at
      postnatal day P17, as expected since the capillary density increases up to P17
      when the microvasculature matures.

PMID- 15847579
TI  - Improved sensitivity to cerebral hemodynamics during brain activation with a time
      gated optical system: analytical model and experimental validation.
AB  - Time domain (TD) diffuse optical measurement systems are being applied to
      neuroimaging, where they can detect hemodynamics changes associated with cerebral
      activity. We show that TD systems can provide better depth sensitivity than the
      more traditional continuous wave (CW) systems by gating late photons, which carry
      information about deep layers of the brain, and rejecting early light, which is
      sensitive to the superficial physiological signal clutter. We use an analytical
      model to estimate the contrast due to an activated region of the brain, the
      instrumental noise of the systems, and the background signal resulting from
      superficial physiological signal clutter. We study the contrast-to-noise ratio
      and the contrast-to-background ratio as a function of the activation depth and of
      the source-detector separation. We then present experimental results obtained
      with a time-gated instrument on the motor cortex during finger-tapping exercises.
      Both the model and the experimental results show a similar contrast-to-noise
      ratio for CW and TD, but that estimation of the contrast is experimentally
      limited by background fluctuations and that a better contrast-to-background ratio
      is obtained in the TD case. Finally, we use the time-gated measurements to
      resolve in depth the brain activation during the motor stimulus.

PMID- 15847580
TI  - Eigenvector-based spatial filtering for reduction of physiological interference
      in diffuse optical imaging.
AB  - Diffuse optical imaging is an effective technique for noninvasive functional
      brain imaging. However, the measurements respond to systemic hemodynamic
      fluctuations caused by the cardiac cycle, respiration, and blood pressure, which
      may obscure or overwhelm the desired stimulus-evoked response. Previous work on
      this problem employed temporal filtering, estimation of systemic effects from
      background pixels, or modeling of interference signals with predefined basis
      functions, with some success. However, weak signals are still lost in the
      interference, and other complementary methods are desirable. We use the spatial
      behavior of measured baseline signals to identify the interference subspaces. We
      then project signals components in this subspace out of the stimulation data. In
      doing so, we assume that systemic interference components will be more global
      spatially, with higher energy, than the stimulus-evoked signals of interest.
      Thus, the eigenvectors corresponding to the largest eigenvalues of an appropriate
      correlation matrix form the basis for an interference subspace. By projecting the
      data onto the orthogonal nullspace of these eigenvectors, we can obtain more
      localized response, as reflected in improved contrast-to-noise ratio and
      correlation coefficient maps.

PMID- 15847581
TI  - Wavelength dependence of crosstalk in dual-wavelength measurement of oxy- and
      deoxy-hemoglobin.
AB  - In near-IR spectroscopy, the concentration change in oxy- and deoxyhemoglobin in
      tissue is calculated from the change in the detected intensity of light at two
      wavelengths by solving the simultaneous equation based on the modified Lambert
      Beer law. The wavelength-independent constant or mean optical path length is
      usually assigned to the term of partial optical path length in the simultaneous
      equation. This insufficient optical path length in the calculation causes
      crosstalk between the concentration change in oxy- and deoxyhemoglobin. We
      investigate the crosstalk in the dual-wavelength measurement of oxy- and
      deoxyhemoglobin theoretically by Monte Carlo simulation to discuss the optimal
      wavelength pair to minimize the crosstalk. The longer wavelength of the dual
      wavelength measurement is fixed at 830 nm and the shorter wavelength is varied
      from 650 to 780 nm. The optimal wavelength range for pairing with 830 nm for the
      dual-wavelength measurement of oxy- and deoxyhemoglobin is from 690 to 750 nm.
      The mean optical path length, which can be obtained by time- and phase-resolved
      measurement, is effective to reduce the crosstalk in the results of dual
      wavelength measurement.

PMID- 15847582
TI  - Selective removal of composite sealants with near-ultraviolet laser pulses of
      nanosecond duration.
AB  - It is often necessary to replace pit and fissure sealants and composite
      restorations. This task is complicated by the necessity for complete removal of
      the remaining composite to enable suitable adhesion of new composite. Previous
      studies have shown that 355-nm laser pulses from a frequency-tripled Nd:YAG laser
      can selectively remove residual composite after orthodontic bracket removal on
      enamel surfaces. Our objective is to determine if such laser pulses are suitable
      for selective removal of composite pit and fissure sealants and restorations.
      Optical coherence tomography is used to acquire optical cross sections of the
      occlusal topography nondestructively before sealant application, after sealant
      application, and after sealant removal. Thermocouples are used to monitor the
      temperature in the pulp chamber during composite removal under clinically
      relevant ablation rates, i.e., 30 Hz and 30 mJ/pulse. At an irradiation intensity
      of 1.3 J/cm2, pit and fissure sealants are completely removed without visible
      damage to the underlying enamel. At intensities above 1.5 J/cm2, incident laser
      pulses remove the resin layer while at the same time preferentially etching the
      surface of the enamel. Temperature excursions in the pulp chamber of extracted
      teeth are limited to less than 5 degrees C if air-cooling is used during the
      rapid removal (1 to 2 min) of sealants, water-cooling is not necessary. Selective
      removal of composite restorative materials is possible without damage to the
      underlying sound tooth structure.

PMID- 15847583
TI  - Combined intracellular three-dimensional imaging and selective nanosurgery by a
      nonlinear microscope.
AB  - We use near-IR femtosecond laser pulses for a combination of microscopy and
      nanosurgery on fluorescently labeled structures within living cells. Three
      dimensional reconstructions of microtubule structures tagged with green
      fluorescent protein (GFP) are made during different phases of the cell cycle.
      Further, the microtubules are dissected using the same laser beam but with a
      higher laser power than for microscopy. We establish the viability of this
      technique for the cells of a fission yeast, which is a common model to study the
      mechanics of cell division. We show that nanosurgery can be performed with
      submicrometer precision and without visible collateral damage to the cell. The
      energy is primarily absorbed by the GFP molecules, and not by other native
      structures in the cell. GFP is particularly suitable for multiphoton excitation,
      as its excitation wavelength near 900 nm is benign for most cellular structures.
      The ability to use GFP to label structures for destruction by multiphoton
      excitation may be a valuable tool in cell biology.

PMID- 15847584
TI  - Red fluorescent protein eqFP611 and its genetically engineered dimeric variants.
AB  - The red fluorescent protein (FP) eqFP611 from the sea anemone Entacmaea
      quadricolor shows favorable properties for applications as a molecular marker.
      Like other anthozoan FPs, it forms tetramers at physiological concentrations. The
      interactions among the monomers, however, are comparatively weak, as inferred
      from the dissociation into monomers in the presence of sodium dodecyl sulfate
      (SDS) or at high dilution. Analysis at the single-molecule level revealed that
      the monomers are highly fluorescent. For application as fusion markers, monomeric
      FPs are highly desirable. Therefore, we examine the monomer interfaces in the x
      ray structure of eqFP611 to provide a basis for the rational design of monomeric
      variants. The arrangement of the four beta cans is very similar to that of other
      green fluorescent protein (GFP-like) proteins such as DsRed and RTMS5. A variety
      of structural features of the tetrameric interfaces explain the weak subunit
      interactions in eqFP611. We produce functional dimeric variants by introducing
      single point mutations in the A/B interface (Thr122Arg, Val124Thr). By contrast,
      structural manipulations in the A/C interface result in essentially complete loss
      of fluorescence, suggesting that A/C interfacial interactions play a crucial role
      in the folding of eqFP611 into its functional form.

PMID- 15847585
TI  - Broadband reflectance measurements of light penetration, blood oxygenation,
      hemoglobin concentration, and drug concentration in human intraperitoneal tissues
      before and after photodynamic therapy.
AB  - We evaluate Photofrin-mediated photodynamic therapy (PDT) in a phase 2 clinical
      trial as an adjuvant to surgery to treat peritoneal carcinomatosis. We extract
      tissue optical [reduced scattering (mu(s)'), absorption (mu(a)), and attenuation
      coefficients (mu(eff))] and physiological [blood oxygen saturation (%S(t)O2),
      total hemoglobin concentration (THC), and photosensitizer concentration
      (c(Photofrin))] properties in 12 patients using a diffuse reflectance instrument
      and algorithms based on the diffusion equation. Before PDT, in normal
      intraperitoneal tissues %S(t)O2 and THC ranged between 32 to 100% and 19 to 263
      microM, respectively; corresponding data from tumor tissues ranged between 11 to
      44% and 61 to 224 microM. Tumor %S(t)O2 is significantly lower than oxygenation
      of normal intraperitoneal tissues in the same patients. The mean (+/-standard
      error of mean) penetration depth (delta) in millimeters at 630 nm is 4.8(+/-0.6)
      for small bowel, 5.2 (+/-0.67) for large bowel, 3.39(+/-0.29) for peritoneum,
      5.19(+/-1.4) for skin, 1.0(+/-0.1) for liver, and 3.02(+/-0.66) for tumor.
      c(Photofrin) in micromolars is 4.9(+/-2.3) for small bowel, 4.8(+/-2.3) for large
      bowel, 3.0 (+/-1.0) for peritoneum, 2.5(+/-0.9) for skin, and 7.4(+/-2.8) for
      tumor. In all tissues examined, mean c(Photofrin) tends to decrease after PDT,
      perhaps due to photobleaching. These results provide benchmark in-vivo tissue
      optical property data, and demonstrate the feasibility of in-situ measurements
      during clinical PDT treatments.

PMID- 15847586
TI  - Raman microspectroscopy and imaging provides insights into heme aggregation and
      denaturation within human erythrocytes.
AB  - The oxygenation process of a human erythrocyte is monitored using a Raman
      microimaging technique. Raman images of the 1638 cm(-1) band are recorded in the
      oxygenated and deoxygenated state using only 120 s of laser exposure and
      approximately 1 mW of defocused laser power. The images show hemoglobin
      oxygenating and deoxygenating within the cell. Prolonged laser imaging exposure
      (<180 s) at low temperatures results in photoinduced and/or thermal degradation.
      The effect of thermal degradation is investigated by recording spectra of
      erythrocytes as a function of temperature between 4 and 52 degrees C. Five bands
      at 1396, 1365, 1248, 972, and 662 cm(-1) are identified as markers for heme
      aggregation. Raman images recorded of cells after prolonged laser exposure appear
      to show heme aggregation commencing in the middle and moving toward the periphery
      of the cell. UV-visible spectra of erythrocytes show the Soret band to be broader
      and red shifted (approximately 3 nm) at temperatures between 45 and 55 degrees
      indicative of excitonic interactions. It is postulated that the enhancement of
      the aggregation marker bands observed at 632.8-nm excitation results primarily
      from excitonic interactions between the aggregated hemes in response to protein
      denaturation. The results have important medical implications in detecting and
      monitoring heme aggregation associated with hemopathies such as sickle cell
      disease.

PMID- 15847587
TI  - Photothermal responses of individual cells.
AB  - Photothermal (PT) responses of individual intact cells are studied with a thermal
      lens dual-laser scheme. A multiparameter model for analysis of PT responses as a
      function of cell size, structure, and optical properties is suggested and
      verified experimentally for living cells, red blood cells, lymphocytes, tumor
      cells (K 562), hepatocytes, and miocytes, by applying pulsed laser radiation at
      532 nm for 10-ns duration. PT responses for noninvasive and damaging modes of
      laser-cell interaction are investigated. It is shown theoretically and
      experimentally that specific optical and structural features of cells influence
      the polarity, shape, front, and tail lengths of their PT responses. Common for
      different cells, features of PT responses are evaluated. It is found that in
      cells with a highly heterogeneous light-absorbing structure, the PT response of a
      whole cell differs from that of the local absorbing area. The model suggested
      allows us to interpret PT responses from single cells and to compare cells in
      terms of their diameter, degree of spatial heterogeneity of light absorbance, and
      laser-induced damage thresholds.

PMID- 15847588
TI  - 3-D simulation of light scattering from biological cells and cell
      differentiation.
AB  - A 3-D code for solving the set of Maxwell equations with the finite-difference
      time-domain method is developed for simulating the propagation and scattering of
      light in biological cells under realistic conditions. The numerical techniques
      employed in this code include the Yee algorithm, absorbing boundary conditions,
      the total field/scattered field formulation, the discrete Fourier transformation,
      and the near-to-far field transform using the equivalent electric and magnetic
      currents. The code is capable of simulating light scattering from any real cells
      with complex internal structure at all angles, including backward scattering. The
      features of the scattered light patterns in different situations are studied in
      detail with the objective of optimizing the performance of cell diagnostics
      employing cytometry. A strategy for determining the optimal angle for measuring
      side scattered light is suggested. It is shown that cells with slight differences
      in their intrastructure can be distinguished with two-parameter cytometry by
      measuring the side scattered light at optimal angles.

PMID- 15847589
TI  - Synergy effects between organic and inorganic UV filters in sunscreens.
AB  - The influence of the synergy effects between organic and inorganic UV filter
      substances on the sun protection factor (SPF) of topically applied sunscreen
      formulations is investigated. The medium is considered to have reflection,
      absorption, and scattering properties. The distribution of photons in this medium
      is investigated by Monte Carlo calculation. Typical optical parameters of the
      skin and substances are used to characterize the synergy effect. The results of
      the model calculation are checked by in vitro and in vivo measurements
      investigating the influence of different types of scattering microparticles on
      the absorption efficacy of topically applied formulations. It is found that the
      inorganic filter substances act as scattering microparticles in the upper skin
      layers. They increase the optical pathway of the photons in the topically applied
      absorbing formulation also localized there. In this way, more photons are
      absorbed, increasing the SPF. The results obtained are important for the
      optimization of the SPF of sunscreen formulation containing organic and inorganic
      UV-filter components.

PMID- 15847590
TI  - Determination of penetration profiles of topically applied substances by means of
      tape stripping and optical spectroscopy: UV filter substance in sunscreens.
AB  - Penetration profiles of topically applied drugs and cosmetic products provide
      important information on their efficacy. The application of tape stripping in
      combination with UV/VIS spectroscopy is checked to determine the local position
      of topically applied substances inside the stratum corneum, the penetration
      profile. The amount of corneocytes removed with each tape strip is quantified via
      the particle-dependent absorption, the pseudoabsorption, in the visible spectral
      range. The concentration of a typical UV filter substance, 4-methylbenzylidene
      camphor, is determined by optical spectroscopy using the tape strips removed
      originally. In this case, a time-dependent increase in the absorbance must be
      taken into account. Laser scanning microscopic investigations confirm that the
      nonhomogeneous distribution of the filter substance, on the strips, can explain
      this spectroscopic behavior. When reaching a homogeneous distribution, the UV
      spectroscopic signal reflects the correct concentration. These spectroscopic
      values are compared with high performance liquid chromatography (HPLC) data. The
      values obtained with both methods for the concentrations of 4-methylbenzylidene
      camphor are in good agreement. The data obtained are used to illustrate the
      determination of a penetration profile of a UV filter substance. The results
      demonstrate that the described protocol is well suited to characterize, in a
      simple manner, topically applied substances that have a characteristic UV/VIS
      absorption band.

PMID- 15847591
TI  - Polarization visualization and selection of biotissue image two-layer scattering
      medium.
AB  - We analyze and experimentally test the concept of laser polarization biotissue
      probing. The methods of increasing the SNR in coherent images of the optically
      anisotropic architectonics of the morphological biotissue structure are
      considered. The possibilities of polarization selection and contrasting of such
      images screened by other biotissues are examined. The influence of the
      depolarization degree of the scattered background on the SNR is investigated. The
      possibilities of polarization correction of the probing beam for contrasting
      biotissue images are analyzed.

PMID- 15847592
TI  - Combining multispectral polarized light imaging and confocal microscopy for
      localization of nonmelanoma skin cancer.
AB  - Multispectral polarized light imaging (MSPLI) enables rapid inspection of a
      superficial tissue layer over large surfaces, but does not provide information on
      cellular microstructure. Confocal microscopy (CM) allows imaging within turbid
      media with resolution comparable to that of histology, but suffers from a small
      field of view. In practice, pathologists use microscopes at low and high power to
      view tumor margins and cell features, respectively. Therefore, we study the
      combination of CM and MSPLI for demarcation of nonmelanoma skin cancers. Freshly
      excised thick skin samples with nonmelanoma cancers are rapidly stained with
      either toluidine or methylene blue dyes, rinsed in acetic acid, and imaged using
      MSPLI and CM. MSPLI is performed at 630, 660, and 750 nm. The same specimens are
      imaged by reflectance CM at 630, 660, and 830 nm. Results indicate that CM and
      MSPLI images are in good correlation with histopathology. Cytological features
      are identified by CM, and tumor margins are delineated by MSPLI. A combination of
      MSPLI and CM appears to be complementary. This combined in situ technique has
      potential to guide cancer surgery more rapidly and at lower cost than
      conventional histopathology.

PMID- 15847593
TI  - Intensity profiles of linearly polarized light backscattered from skin and tissue
      like phantoms.
AB  - Anisotropy of mouse and human skin is investigated in vivo using polarized
      videoreflectometry. An incident beam (linearly polarized, wavelength 650 nm) is
      focused at the sample surface. Two types of tissuelike media are used as controls
      to verify the technique: isotropic delrin and highly anisotropic demineralized
      bone with a priori knowledge of preferential orientation of collagen fibers. Equi
      intensity profiles of light, backscattered from the sample, are fitted with
      ellipses that appear to follow the orientation of the collagen fibers. The ratio
      of the ellipse semiaxes is well correlated with the ratio of reduced scattering
      coefficients obtained from radial intensity distributions. Variation of equi
      intensity profiles with distance from the incident beam is analyzed for different
      initial polarization states of the light and the relative orientation of
      polarization filters for incident and backscattered light. For the anisotropic
      media (demineralized bone and human and mouse skin), a qualitative difference
      between intensity distributions for cross- and co-polarized orientations of the
      polarization analyzer is observed up to a distance of 1.5 to 2.5 mm from the
      entry point. The polarized videoreflectometry of the skin may be a useful tool to
      assess skin fibrosis resulting from radiation treatment.

PMID- 15847594
TI  - Fiber optic near-infrared Raman spectroscopy for clinical noninvasive
      determination of water content in diseased skin and assessment of cutaneous
      edema.
AB  - Currently, measuring Raman spectra of tissues of living patients online and in
      real time, collecting the spectra in a very short measurement time, and allowing
      diagnosis immediately after the spectrum is recorded from any body region, are
      specific advantages that fiber optic near-infrared Raman spectroscopy (NIR RS)
      might represent for in vivo clinical applications in dermatology. We discuss
      various methodological aspects and state of the art of fiber optic NIR RS in
      clinical and experimental dermatology to outline its present advantages and
      disadvantages for measuring skin in vivo, particularly its water content. Fiber
      optic NIR Fourier transform (FT) RS has been introduced to dermatological
      diagnostics to obtain information regarding the molecular composition of the skin
      up to several hundred micrometers below the skin surface in a relatively fast
      nondestructive manner. This has been especially important for probing for in vivo
      assessment of cutaneous (intradermal) edema in patients patch test reactions.
      Fiber optic NIR FT Raman spectrometers still require further technological
      developments and optimization, extremely accurate water concentration
      determination and its intensity calculation in skin tissue, and for clinical
      applications, a reduction of measurement time and their size. Another promising
      option could be the possibility of applying mobile and compact fiber optic charge
      coupled device (CCD)-based equipment in clinical dermatology.

PMID- 15847595
TI  - Kerr-gated time-resolved Raman spectroscopy of equine cortical bone tissue.
AB  - Picosecond time-resolved Raman spectroscopy in equine cortical bone tissue is
      demonstrated. Using 400-nm pulsed laser excitation (1 ps at 1 kHz) it is shown
      that Kerr cell gating with a 4-ps window provides simultaneously time-resolved
      rejection of fluorescence and time-resolved Raman scatter enabling depth
      profiling through tissue. The Raman shifts are the same as those observed by
      conventional cw Raman spectroscopy using deep-red or near-infrared lasers. The
      time decay of Raman photons is shown to fit an inverse square root of time
      function, suggesting propagation by a diffusive mechanism. Using polystyrene
      behind a bone specimen, it is shown that the 400-nm laser light penetrates at
      least 0.31 mm below the surface of a fully mineralized bone tissue specimen and
      generates observable bone Raman scatter (approximately 415 to 430 nm) through
      most of this depth. These novel results demonstrate great promise for in vivo
      applications for studying diseased bone tissue, and ways to optimize the setup
      are discussed.

PMID- 15847596
TI  - Fourier transform infrared imaging spectroscopy analysis of collagenase-induced
      cartilage degradation.
AB  - Collagenase treatment of cartilage serves as an in vitro model of the
      pathological collagen degradation that occurs in the disease osteoarthritis (OA).
      Fourier transform infrared imaging spectroscopic (FT-IRIS) analysis of
      collagenase-treated cartilage is performed to elucidate the molecular origin of
      the spectral changes previously found at the articular surface of human OA
      cartilage. Bovine cartilage explants are treated with 0.1% collagenase for 0, 15,
      or 30 min. In situ collagen cleavage is assessed using immunofluorescent staining
      with an antibody specific for broken type II collagen. The FT-IRIS analysis of
      the control and treated specimens mirrors the differences previously found
      between normal and OA cartilage using an infrared fiber optic probe (IFOP). With
      collagenase treatment, the amide II/1338 cm(-1) area ratio increases while the
      1238 cm(-1)/1227 cm(-1) peak ratio decreases. In addition, polarized FT-IRIS
      demonstrates a more random orientation of the collagen fibrils that correlate
      spatially with the immunofluorescent-determined regions of broken type II
      collagen. We can therefore conclude that the spectral changes observed in the
      collagenase-treated cartilage, and similarly in OA cartilage, arise from changes
      in collagen structure. These findings support the use of mid-infrared spectral
      analysis, in particular the minimally invasive IFOP, as potential techniques for
      the diagnosis and management of degenerative joint diseases such as
      osteoarthritis.

PMID- 15847597
TI  - Simple peak shift analysis of time-of-flight data with a slow instrumental
      response function.
AB  - Analysis of time-of-flight (TOF) data is sometimes limited by the instrumental
      response function, and optical parameters are extracted from the observed
      response curve by several mathematical methods, such as deconvolution. In
      contrast to this, we demonstrate that a method using shifts of the peak time of
      the response curve with different source-detector separations can yield the
      average path length of the light traveling in a tissue-like sample without
      deconvolution. In addition, combining the intensity information allows us to
      separate the scattering and absorption coefficients. This simple method is more
      robust in signal-to-noise ratio than the moment analysis, which also does not
      require the deconvolution procedure, because the peak position is not
      significantly dependent on the baseline fluctuation and the contamination of the
      scattering. The analysis is demonstrated by TOF measurements of an Intralipid
      solution at 800 nm, and is applied to the measurements at 1.29 microm, where the
      temporal response of photomultiplier tubes is not sufficiently good.

PMID- 15847602
TI  - Yersinia outer proteins: role in modulation of host cell signaling responses and
      pathogenesis.
AB  - A type III secretion system (TTSS) is encoded on a virulence plasmid that is
      common to three pathogenic Yersinia species: Y. enterocolitica, Y.
      pseudotuberculosis, and Y. pestis. Pathogenic Yersinia species require this TTSS
      to survive and replicate within lymphoid tissues of their animal or human hosts.
      A set of pathogenicity factors, including those known as Yersinia outer proteins
      (Yops), is exported by this system upon bacterial infection of host cells. Two
      translocator Yops (YopB and YopD) insert into the host plasma membrane and
      function to transport six effector Yops (YopO, YopH, YopM, YopT, YopJ, and YopE)
      into the cytosol of the host cell. Effector Yops function to counteract multiple
      signaling responses in the infected host cell. The signaling responses
      counteracted by Yops are initiated by phagocytic receptors, Toll-like receptors,
      translocator Yops, and additional mechanisms. Innate and adaptive immune
      responses are thwarted as a consequence of Yop activities. A biochemical function
      for each effector Yop has been established, and the importance of these proteins
      for the pathogenesis process is being elucidated. This review focuses on the
      biochemical functions of Yops, the signaling pathways they modulate, and the role
      of these proteins in Yersinia virulence.

PMID- 15847604
TI  - Ca2+ accumulation into acidic organelles mediated by Ca2+- and vacuolar H+
      ATPases in human platelets.
AB  - Most physiological agonists increase cytosolic free [Ca2+]c (cytosolic free Ca2+
      concentration) to regulate a variety of cellular processes. How different stimuli
      evoke distinct spatiotemporal Ca2+ responses remains unclear, and the presence of
      separate intracellular Ca2+ stores might be of great functional relevance. Ca2+
      accumulation into intracellular compartments mainly depends on the activity of
      Ca2+- and H+-ATPases. Platelets present two separate Ca2+ stores differentiated
      by the distinct sensitivity to thapsigargin and TBHQ [2,5-di-(t-butyl)-1,4
      hydroquinone]. Although one store has long been identified as the dense tubular
      system, the nature of the TBHQ-sensitive store remains uncertain. Treatment of
      platelets with GPN (glycylphenylalanine-2-naphthylamide) impaired Ca2+ release by
      TBHQ and reduced that evoked by thrombin. In contrast, GPN did not modify Ca2+
      mobilization stimulated by ADP or AVP ([arginine]vasopressin). Treatment with
      nigericin, a proton carrier, and bafilomycin A1, an inhibitor of the vacuolar H+
      ATPase, to dissipate the proton gradient into acidic organelles induces a
      transient increase in [Ca2+]c that was abolished by previous treatment with the
      SERCA (sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase) 3 inhibitor TBHQ. Depleted
      acidic stores after nigericin or bafilomycin A1 were refilled by SERCA 3.
      Thrombin, but not ADP or AVP, reduces the rise in [Ca2+]c evoked by nigericin and
      bafilomycin A1. Our results indicate that the TBHQ-sensitive store in human
      platelets is an acidic organelle whose Ca2+ accumulation is regulated by both
      Ca2+- and vacuolar H+-ATPases.

PMID- 15847605
TI  - Evidence for mitochondrial localization of a novel human sialidase (NEU4).
AB  - Based on the human cDNA sequence predicted to represent the NEU4 sialidase gene
      in public databases, a cDNA covering the entire coding sequence was isolated from
      human brain and expressed in mammalian cells. The cDNA encodes two isoforms: one
      possessing an N-terminal 12-amino-acid sequence that is predicted to be a
      mitochondrial targeting sequence, and the other lacking these amino acids.
      Expression of the isoforms is tissue specific, as assessed by reverse
      transcription-PCR. Brain, muscle and kidney contained both isoforms; liver showed
      the highest expression, and the short form was predominant in this organ. In
      transiently transfected COS-1 cells, enzyme activity was markedly increased with
      gangliosides as well as with glycoproteins and oligosaccharides as substrates
      compared with the control levels. This differs from findings with other human
      sialidases. Although the isoforms were not distinguishable with regard to
      substrate specificity, they exhibited differential subcellular localizations.
      Immunofluorescence microscopy and biochemical fractionation demonstrated that an
      exogenously expressed haemagglutinin-tagged long form of NEU4 was concentrated in
      mitochondria in several human culture cell types, whereas the short form was
      present in intracellular membranes, indicating that the sequence comprising the N
      terminal 12 amino acid residues acts as a targeting signal for mitochondria. Co
      localization of the long form to mitochondria was further supported by efficient
      targeting of the N-terminal region fused to enhanced green fluorescent protein,
      and by the targeting failure of a mutant with an amino acid substitution in this
      region. NEU4 is possibly involved in regulation of apoptosis by modulation of
      ganglioside G(D3), which accumulates in mitochondria during apoptosis and is the
      best substrate for the sialidase.

PMID- 15847606
TI  - Quantitative genotyping of single-nucleotide polymorphisms by allele-specific
      oligonucleotide hybridization on DNA microarrays.
AB  - Genotyping of SNPs (single-nucleotide polymorphisms) has challenged the
      development of several novel techniques. Most of these methods have been
      introduced to discriminate binary SNPs in diploid species. In the present study,
      the quantitative genotyping of SNPs in natural DNA pools of a polyploid organism
      via DNA microarrays was analysed. Three randomly selected SNP loci were genotyped
      in the tetraploid species potato (Solanum tuberosum). For each SNP, 24 oligomers
      were designed, 12 with forward and 12 with reverse orientation. They contained
      the polymorphic site at one of the positions 11, 14 and 17. Several steps of
      optimizations were performed, including the 'materials' used and the
      establishment of hybridization conditions. Glass surfaces were either epoxy- or
      aldehyde-modified, and allele-specific oligonucleotides contained either SH or
      NH2 groups. Hybridization stringency conditions were established by varying the
      concentration of formamide in the hybridization buffer. For SNP BA213c14t7/403,
      the quantitative discrimination between all four different naturally occurring
      genotypes could be demonstrated.

PMID- 15847607
TI  - Cancer cell injury by cytotoxins from cobra venom is mediated through lysosomal
      damage.
AB  - Cytotoxins from cobra venom are known to manifest cytotoxicity in various cell
      types. It is widely accepted that the plasma membrane is a target of cytotoxins,
      but the mechanism of their action remains obscure. Using the confocal spectral
      imaging technique, we show for the first time that cytotoxins from cobra venom
      penetrate readily into living cancer cells and accumulate markedly in lysosomes.
      Cytotoxins CT1 and CT2 from Naja oxiana, CT3 from Naja kaouthia and CT1 from Naja
      haje are demonstrated to possess this property with respect to human lung
      adenocarcinoma A549 and promyelocytic leukaemia HL60 cells. Immobilized plasma
      membrane binding accompanies the internalization of CT3 from Naja kaouthia in the
      HL60 cells, but it is very weak for other cytotoxins. Detectable membrane binding
      is not a property of any of the cytotoxins tested in A549 cells. The kinetics and
      concentration-dependence of cytotoxin accumulation in lysosomes correlate well
      with their cytotoxic effects. On the basis of the results obtained, we propose
      that lysosomes are a primary target of the lytic action of cytotoxins. Plasma
      membrane permeabilization seems to be a downstream event relative to lysosome
      rupture. Direct damage to the plasma membrane may be a complementary mechanism,
      but its relative contribution to the cytotoxic action depends on the cytotoxin
      structure and cell type.

PMID- 15847609
TI  - A cold-active pectin lyase from the psychrophilic and basidiomycetous yeast
      Cystofilobasidium capitatum strain PPY-1.
AB  - In the present study we purified a cold-active PNL (pectin lyase) from the
      extracellular fraction of the PPY (pectinolytic and psychrophilic yeast)
      Cystofilobasidium capitatum strain PPY-1. The purified PNL has a molecular mass
      of approx. 42 kDa, and its N-terminal amino acid sequence is
      ATGVTGSAYGFATGTTGGGSATPAY, which exhibits 72% identity with that of PNL F from
      Aspergillus niger. The purified PNL exhibited high activity at 10 degrees C,
      although its optimum temperature was 40 degrees C. Moreover, Km and Vmax for
      pectin as a substrate were found to have values 36.6 mg/ml and 3000 units/mg
      respectively. These findings may indicate that this enzyme from strain PPY-1 is a
      cold-active PNL that is able to degrade pectin compounds at low temperature.

PMID- 15847608
TI  - HIV-1 Nef regulates the release of superoxide anions from human macrophages.
AB  - The NADPH oxidase enzymatic complex participates in the oxidative burst by
      producing ROS (reactive oxygen species). Altered levels of ROS production may
      have pathogenetic implications due to the loss of some innate immune functions
      such as oxidative burst and phagocytosis. Considering that HIV-1 Nef protein
      plays a primary role in AIDS pathogenesis, by affecting the immune system, we
      sought to dissect possible effects of Nef on the release of superoxide anions. We
      show here that the inducible expression of Nef in human phagocytic cells
      modulates the superoxide release in a biphasic manner. In particular, an early
      Nef-induced increase of the superoxide release was followed by a dramatic
      decrease starting from 10 h after the Nef induction. This was observed whatever
      the presence of cell activators such as GM-CSF (granulocyte/macrophage colony
      stimulating factor) or fMLP (N-formyl-L-methionyl-L-leucyl-L-phenylalanine).
      Whereas the early increase in superoxide release is probably the result of the
      already described Nef-dependent activation of PAK-2 (p21-activated kinase 2)
      Rac2, we were interested in investigating the mechanisms underlying the late
      inhibition of superoxide release observed originally. In this regard, we
      individuated at least three independent requirements for the Nef-induced blockade
      of superoxide release: (i) the active protein synthesis; (ii) both the membrane
      localization and the interaction with endocytotic machinery of Nef; and (iii) the
      release of soluble factor(s). Moreover, we observed that IL-10 (interleukin-10)
      inhibits superoxide release, whereas its depletion restored NADPH oxidase
      activity. We propose that the cell membrane-to-lysosome Nef transit leads to the
      synthesis and release of soluble factor(s) and, among them, IL-10 might
      significantly contribute to the inhibition of NAPDH oxidase activity.

PMID- 15847610
TI  - A factorial experiment for optimizing the PCR conditions in routine genotyping.
AB  - Although most PCRs would produce proper PCR products when first tried, a general
      optimization is required to yield the best results. This optimization is often
      achieved by changing one factor at a time. However, this may lead to suboptimal
      results, since interactions between conditions are difficult to detect with this
      approach. In the present study, we describe the factorial optimization of PCR
      conditions for microsatellite genotyping, by introducing small systematic
      variations in conditions during the genotyping process. The hypothesis was that
      small changes will not affect genotyping results, but will provide information
      about the optimality of current conditions. The conditions to vary were the
      concentrations of buffer, MgCl(2), dNTPs, primers, Taq polymerase and DNA, the
      annealing temperature (T(a)) and the number of cycles. We show that, by a 2(8)
      factorial experiment, it is possible to identify not only the factors responsible
      for obtaining good results, but also those responsible for bad results. However,
      the condition leading to the highest signals is not necessarily the best
      operational condition. The best operational condition is minimally sensitive to
      random pipetting fluctuations and yields reliable genotypes as well.

PMID- 15847611
TI  - Time to change attitudes to tobacco: product regulation over five years?

PMID- 15847612
TI  - Marijuana use and driver risks: the role of epidemiology and experimentation.

PMID- 15847613
TI  - World Health Organization's global action on alcohol: resources required to match
      the rhetoric.

PMID- 15847615
TI  - Conversation with Harold Holder.

PMID- 15847614
TI  - The integrity of the science base: a test case.

PMID- 15847616
TI  - Iatrogenic effects of psychosocial interventions for substance use disorders:
      prevalence, predictors, prevention.
AB  - AIMS: To examine the prevalence and personal and intervention-related predictors
      of potential iatrogenic effects associated with psychosocial interventions for
      substance use disorders and provide a conceptual framework to guide further
      research on such effects. METHOD: A review of relevant studies focuses on the
      prevalence and predictors of potential iatrogenic effects of psychosocial
      treatment and prevention programs for substance use disorders. RESULTS: Between
      7% and 15% of patients who participate in psychosocial treatment for substance
      use disorders may be worse off subsequent to treatment than before. In addition,
      several controlled trials of substance use prevention have shown some apparent
      iatrogenic effects, including more positive expectations about substance use and
      a rise in alcohol use and alcohol-related problems. Probable person-related
      predictors of deterioration associated with treatment include younger age and
      unmarried status, more serious current diagnoses and substance use problems and
      more psychiatric and interpersonal problems. Probable intervention-related
      predictors of deterioration include lack of bonding; lack of monitoring;
      confrontation, criticism and high emotional arousal; deviancy modeling; and
      stigma, low or inappropriate expectations and lack of challenge. CONCLUSION: A
      significant minority of individuals with substance use problems appear to
      deteriorate during or shortly after participation in treatment or prevention
      programs. Safety standards and monitoring procedures are needed to routinely
      identify potential adverse consequences of intervention programs; research is
      needed to clarify whether deterioration is due to iatrogenic effects of
      interventions and to identify new approaches to counteract any such effects.

PMID- 15847617
TI  - Marijuana use and car crash injury.
AB  - AIMS: To investigate the relationship between marijuana use prior to driving,
      habitual marijuana use and car crash injury. DESIGN AND SETTING: Population based
      case-control study in Auckland, New Zealand. PARTICIPANTS: Case vehicles were all
      cars involved in crashes in which at least one occupant was hospitalized or
      killed anywhere in the Auckland region, and control vehicles were a random sample
      of cars driving on Auckland roads. The drivers of 571 case and 588 control
      vehicles completed a structured interview. MEASUREMENTS: Self reported marijuana
      use in the 3 hours prior to the crash/survey and habitual marijuana use over the
      previous 12 months were recorded, along with a range of other variables
      potentially related to crash risk. The main outcome measure was hospitalization
      or death of a vehicle occupant due to car crash injury. FINDINGS: Acute marijuana
      use was significantly associated with car crash injury, after controlling for the
      confounders age, gender, ethnicity, education level, passenger carriage, driving
      exposure and time of day (OR 3.9, 95% CI 1.2-12.9). However, after adjustment for
      these confounders plus other risky driving at the time of the crash (blood
      alcohol concentration, seat-belt use, travelling speed and sleepiness score), the
      effect of acute marijuana intake was no longer significant (OR 0.8, 95% CI 0.2
      3.3). There was a strong significant association between habitual use and car
      crash injury after adjustment for all the above confounders plus acute use prior
      to driving (OR 9.5, 95% CI 2.8-32.3). CONCLUSIONS: This population-based case
      control study indicates that habitual use of marijuana is strongly associated
      with car crash injury. The nature of the relationship between marijuana use and
      risk-taking is unclear and needs further research. The prevalence of marijuana
      use in this driving population was low, and acute use was associated with
      habitual marijuana use, suggesting that intervention strategies may be more
      effective if they are targeted towards high use groups.

PMID- 15847618
TI  - Cannabis use predicts future psychotic symptoms, and vice versa.
AB  - AIMS: To assess if cannabis use is a risk factor for future psychotic symptoms,
      and vice versa, in adolescents and young adults from the general population.
      DESIGN: Cohort study. SETTING/PARTICIPANTS: 'Zuid Holland' study, a 14-year
      follow-up study of 1580 initially 4-16-year-olds who were drawn randomly from the
      Dutch general population. Because cannabis use is generally condoned in the
      Netherlands, false-negative reports of cannabis use may occur less frequently
      than in countries with stricter drug policies, which supports the value of the
      present study. MEASUREMENTS: Life-time cannabis use and psychotic symptoms,
      assessed with the Composite International Diagnostic Interview (CIDI). FINDINGS:
      Cannabis use, in individuals who did not have psychotic symptoms before they
      began using cannabis, predicted future psychotic symptoms (hazard ratio = 2.81;
      95% confidence interval = 1.79-4.43). However, psychotic symptoms in those who
      had never used cannabis before the onset of psychotic symptoms also predicted
      future cannabis use (hazard ratio = 1.70; 95% confidence interval = 1.13-2.57).
      CONCLUSIONS: The results imply either a common vulnerability with varying order
      of onset or a bi-directional causal relationship between cannabis use and
      psychosis. More research on patterns and timings of these relationships is needed
      to narrow down the possibilities.

PMID- 15847619
TI  - Drug use among female sex workers in Hanoi, Vietnam.
AB  - AIMS: To describe the drug use practices among female sex workers (FSWs) in Hanoi
      and to identify factors associated with their drug injecting. DESIGN, SETTING AND
      PARTICIPANTS: A two-stage cluster survey of 400 FSWs was conducted from June to
      September, 2002. Participating FSWs were both establishment- (160) and street
      based (240), who were practising in seven urban and one suburban districts of
      Hanoi. MEASUREMENTS: Subjects were interviewed face to face using a structured
      questionnaire. FINDINGS: Among the middle-class FSWs, 27% used drugs, of whom 79%
      injected. Among low-class FSWs, 46% used drugs and 85% injected. Among drug-using
      FSWs, 86% had started using drugs within the past 6 years. Among drug-injecting
      FSWs, 81% had started injecting within the past 4 years. Cleaning of injecting
      equipment was not common among those who shared. Having drug-injecting 'love
      mates', drug-using clients, longer residence in Hanoi, more clients and not
      currently cohabiting were found to be independently associated with drug
      injecting among FSWs. CONCLUSIONS: The high prevalence of injecting drug use
      among FSWs makes them susceptible to HIV infection, and is a threat to their
      clients. There is a strong relationship between drug-using FSWs and male drug
      using clients and non-client partners. Intervention to prevent drug use
      initiation among non-drug-using FSWs and harm reduction among drug-using FSWs are
      urgently needed.

PMID- 15847620
TI  - HCV viremia is associated with drug use in young HIV-1 and HCV coinfected
      pregnant and non-pregnant women.
AB  - AIMS: Vertical transmission of HCV is increased among HIV-1/HCV coinfected women
      and is related to HCV viral load. In this study we assessed clinical and
      demographic factors associated with HCV viremia in a cohort of young pregnant and
      non-pregnant mothers coinfected with HIV-1. DESIGN: A cross-sectional clinic
      based study nested within a prospective cohort study. METHODS: From 1988 to 2000,
      HIV-1 + pregnant and non-pregnant women with children followed in a large
      maternal, child and adolescent HIV-1 clinic were evaluated for HCV infection
      using EIA 3.0. HCV RNA levels were determined for HCV antibody + women using
      polymerase chain reaction. Demographic and clinical characteristics between HCV
      RNA(+) and HCV-RNA(-) women and between pregnant and non-pregnant HIV-1/HCV
      coinfected women were compared using univariate and multivariate analyses.
      FINDINGS: Among 359 HIV-1(+) women, 84 (23%) were HCV-ab + and 49/84 (58%) had
      detectable HCV-RNA in plasma. Median age was 31. CD4 counts, HIV-1 RNA levels and
      demographic characteristics were similar for viremic and non-viremic women and
      pregnant and non-pregnant women. However, viremic women were more likely to
      report a history of (88% versus 43%; P < 0.001) or active injection drug use
      (AIDU) (83% versus 29%; P < 0.001). Logistic regression analysis showed that HCV
      viremia was associated significantly with AIDU (adjusted OR: 15.17; 95% CI: 3.56,
      64.56) after adjusting for age, race, number of sexual partners, pregnancy
      status, CD4 counts and HIV-1 viral load. CONCLUSION: In this cohort of young HIV
      1 and HCV coinfected women, HCV viremia was associated strongly with active
      injection drug use, perhaps due to reinfection or reactivation of HCV. Thus,
      careful evaluation for HCV infection and counseling related to drug use may be
      necessary.

PMID- 15847621
TI  - Transient changes in behaviour lead to heroin overdose: results from a case
      crossover study of non-fatal overdose.
AB  - BACKGROUND AND AIMS: Heroin overdose is a serious consequence of heroin use and
      one of the leading causes of premature death and illness in Australia. Despite
      considerable research effort little is known about the effects of transient
      changes in heroin user behaviour and the links to overdose. This research is the
      first to use a suitable methodology to allow such ephemeral changes and their
      effects on non-fatal heroin overdose to be examined. METHODS: A case-crossover
      design was used in which non-fatal heroin overdose survivors' recall of risk
      behaviours in the 12 hours prior to overdose (hazard period) was compared to
      their recall of risk behaviours in the 12 hours prior to a selected non-overdose
      heroin injection (control period). RESULTS: A total of 155 participants were able
      to provide valid details of hazard and control periods. A dose-response
      relationship was observed between the self-reported amount of heroin used and
      likelihood of overdose (e.g. > AUD50, OR 12.97, 95% CI 2.54-66.31). The use of
      benzodiazepines (OR 28, 95% CI 3.81-205.79) or alcohol (OR 2.88, 95% CI 1.29
      6.43), during the hazard period was related to overdose risk, but the effect of
      alcohol was attenuated by the effect of benzodiazepines. Shifting from private to
      public locations between control and hazard periods was also related to increased
      risk of overdose (OR 3.63, 95% CI 1.66-7.93). CONCLUSIONS: We demonstrate the
      value of a new methodology to explore heroin overdose, as well as discussing its
      limitations and ways to overcome them in future. In terms of our findings,
      overdose prevention messages need to highlight the impact of these transient
      changes in behaviour and to emphasize the risks of using higher doses of heroin
      as well as continuing to emphasize the risks of combining heroin with other
      central nervous system (CNS) depressants. Safer environments for heroin use, such
      as injecting rooms, may also reduce the chances of overdose.

PMID- 15847622
TI  - Is there really a 'J-shaped' curve in the association between alcohol consumption
      and symptoms of depression and anxiety? Findings from the Mater-University Study
      of Pregnancy and its outcomes.
AB  - AIMS: To determine the nature of the association between alcohol consumption and
      symptoms of anxiety and depression in women. DESIGN: Prospective cohort study of
      women (n = 4527) who received antenatal care at a major public hospital (Mater
      Misericordiae Hospital) in South Brisbane between 1981 and 1984 and who have
      follow-up data on alcohol use, depressive and anxiety symptoms over a 14-year
      period. FINDINGS: At the 5-year follow-up there was a 'J-shaped' association
      between alcohol consumption and both symptoms of depression and of anxiety.
      However, at the baseline assessment and the 14-year follow-up alcohol consumption
      was linearly and positively associated with depressive symptoms with increasing
      prevalence of symptoms with greater consumption. At the 5-year follow-up the
      prevalence of depressive and anxiety symptoms among those who were abstainers at
      both baseline and 5-year follow-up was similar to that among those who had been
      previous drinkers and then become abstainers (P = 0.67). Similarly, the
      prevalence of these symptoms was the same at the 14-year follow-up comparing
      those who had been abstainers at baseline, 5-year and 14-year follow-up to those
      who had previously consumed alcohol but were then abstainers. CONCLUSIONS: The
      nature of the association between alcohol consumption and symptoms of depression
      and anxiety may vary across their life course in women. Previous drinkers who
      become abstainers do not appear to be at any higher risk of symptoms of
      depression or anxiety compared to those who always abstained, suggesting that
      increased symptoms in abstainers at age 30 is not due to 'sick quitters'. The
      association of high alcohol consumption with symptoms of depression and anxiety
      may be confounded by low income and smoking.

PMID- 15847623
TI  - Age of onset of drinking and the use of alcohol in adulthood: a follow-up study
      from age 8-42 for females and males.
AB  - AIM: To investigate longitudinally for both genders the relation between the age
      of onset of drinking and several indicators of alcohol use. DESIGN AND SETTING:
      In the Finnish Jyvaskyla Longitudinal Study of Personality and Social
      Development, data have been collected by interviews, inventories, and
      questionnaires. Data on alcohol consumption was gathered at ages 14, 20, 27, 36
      and 42 years; behavioural data at age 8. PARTICIPANTS: A total of 155 women and
      176 men; 90.4% of the original sample consisting of 12 complete school classes in
      1968. MEASUREMENTS: The age of onset of drinking was determined based on
      participants' responses that were closest to the actual age of onset of drinking.
      Four indicators of the adult use of alcohol were used: frequency of drinking,
      binge drinking, Cut-down, Annoyed, Guilt, Eye-opener (CAGE) and Malmo modified
      Michigan Alcoholism Screening Test (Mm-MAST). Socio-emotional behaviour at age 8
      was assessed using teacher ratings and peer nominations. FINDINGS: Early onset of
      drinking was related to the four indicators of the use of alcohol in adulthood
      both in men and women. The level of adult alcohol use and alcohol problems was
      significantly higher in men. The risk for heavy drinking was highest in men and
      women if drinking was started at less than age 16 years. Socio-emotional
      behaviour and school success at age 8 did not predict the age of onset of
      drinking. CONCLUSIONS: Delaying the initiation of drinking from early adolescence
      to late adolescence is an important goal for prevention efforts. No clear risk
      group for early initiators of drinking could be identified on the basis of
      preceding behaviour among 8-year-olds.

PMID- 15847624
TI  - An investigation of the effect of privatization of retail sales of alcohol on
      consumption and traffic accidents in Alberta, Canada.
AB  - AIMS: Privatization of the retail sale of alcohol in Alberta took place primarily
      between the end of the 1980s and the beginning of the 1990s. The aim of this
      study was to evaluate the effects of this privatization on alcohol sales and on
      the incidence of fatal motor vehicle traffic accidents in the province. DATA AND
      METHOD: Interrupted time-series analysis (ARIMA) with a quasi-experimental
      control area design was used, and all series were differenced to remove long-term
      trends. Canada, with the exception of Alberta, was the control area. The effects
      of privatization were measured by means of created privatization variables. In
      the analyses of the effects of privatization on alcohol sales, the inhabitants'
      disposable income and alcohol prices were used as control variables. The study
      period was 1950-2000. When effects on the number of fatal motor vehicle traffic
      accidents were analysed the number of road motor vehicle registrations was used
      as a control variable, and the study period was 1950-98. FINDINGS: Privatization
      had a significant permanent effect on the sale of spirits, but the effect was not
      large enough to affect total sales. The effect on wine and beer sales was not
      significant. There was no significant effect on the number of fatal motor vehicle
      traffic accidents. CONCLUSION: The fact that sales on the wholesale level
      continued to be monopolized, along with the fact that alcohol sales were never
      allowed in ordinary grocery stores, may explain the lack of any larger effects of
      privatization on alcohol sales in Alberta.

PMID- 15847625
TI  - Automatic effects of alcohol cues on sexual attraction.
AB  - AIMS: The present study tested whether suboptimal priming (which may be defined
      as 'under viewing conditions rendering conscious identification highly
      improbable') with alcohol-related stimuli would activate existing expectancies
      about alcohol's effects on sexual desire. It was predicted that alcohol cues,
      relative to non-alcohol cues, would activate expectancies of alcohol's
      aphrodisiac properties. We hypothesized that for men, stronger expectancies in
      this regard would predict an increased tendency to judge women as sexually
      attractive following the alcohol primes. DESIGN: Two experimental studies
      manipulated cue (alcohol versus control) and rating dimension (attractiveness
      versus intelligence). Self-reported alcohol expectancies of sexual desire were
      assessed approximately 1 month prior to the study. Study 2 assessed additional
      expectancy content domains. SETTING AND PARTICIPANTS: Study 1 comprised 82
      undergraduate males and study 2 78 undergraduate males. Studies were conducted at
      the University of Missouri-Columbia, Columbia, Missouri, USA. INTERVENTIONS: In
      both experiments, male participants were suboptimally primed with either alcohol
      related or control words. Following this priming, they were presented with a
      series of photographs of young women and asked to either rate their
      attractiveness or their intelligence. FINDINGS AND CONCLUSIONS: In both studies,
      a three-way interaction between cue, rating dimension and alcohol expectancies
      was found. Within the attractiveness rating condition a two-way interaction was
      found, indicating that in this condition, stronger expectancies that alcohol
      increases sexual desire predicted higher attractiveness ratings after suboptimal
      exposure to alcohol primes. No effects emerged in the intelligence rating
      condition. Discussion centers on implications for sexual risk-taking as well as a
      range of other non-consumptive behaviors.

PMID- 15847626
TI  - Randomized controlled trial of a web-based computer-tailored smoking cessation
      program as a supplement to nicotine patch therapy.
AB  - AIM: To assess the efficacy of World Wide Web-based tailored behavioral smoking
      cessation materials among nicotine patch users. DESIGN: Two-group randomized
      controlled trial. SETTING: World Wide Web in England and Republic of Ireland.
      PARTICIPANTS: A total of 3971 subjects who purchased a particular brand of
      nicotine patch and logged-on to use a free web-based behavioral support program.
      INTERVENTION: Web-based tailored behavioral smoking cessation materials or web
      based non-tailored materials. MEASUREMENTS: Twenty-eight-day continuous
      abstinence rates were assessed by internet-based survey at 6-week follow-up and
      10-week continuous rates at 12-week follow-up. FINDINGS: Using three approaches
      to the analyses of 6- and 12-week outcomes, participants in the tailored
      condition reported clinically and statistically significantly higher continuous
      abstinence rates than participants in the non-tailored condition. In our primary
      analyses using as a denominator all subjects who logged-on to the treatment site
      at least once, continuous abstinence rates at 6 weeks were 29.0% in the tailored
      condition versus 23.9% in the non-tailored condition (OR = 1.30; P = 0.0006); at
      12 weeks continuous abstinence rates were 22.8% versus 18.1%, respectively (OR =
      1.34; P = 0.0006). Moreover, satisfaction with the program was significantly
      higher in the tailored than in the non-tailored condition. CONCLUSIONS: The
      results of this study demonstrate a benefit of the web-based tailored behavioral
      support materials used in conjunction with nicotine replacement therapy. A web
      based program that collects relevant information from users and tailors the
      intervention to their specific needs had significant advantages over a web-based
      non-tailored cessation program.

PMID- 15847627
TI  - A school-based harm minimization smoking intervention trial: outcome results.
AB  - AIMS: To determine the impact of a school-based harm minimization smoking
      intervention compared to traditional abstinence-based approaches. DESIGN, SETTING
      AND PARTICIPANTS: A school-based cluster randomized trial was conducted in Perth,
      Western Australia in 30 government high schools from 1999 to 2000. Over 4000
      students were recruited to participate and schools were assigned randomly to
      either the harm minimization intervention or a standard abstinence-based
      programme. INTERVENTION: The harm minimization intervention comprised eight 1
      hour lessons over 2 years, quitting support from school nurses and enactment of
      policies to support programme components. Comparison schools implemented standard
      abstinence-based programmes and policies. MEASURES: Cigarette smoking was
      categorized at two levels: regular smoking, defined as smoking on 4 or more days
      in the previous week; and 30-day smoking as any smoking within the previous
      month. FINDINGS: At immediate post-test (20 months post-baseline), after
      accounting for baseline differences, school-level clustering effects, socio
      economic status, gender and family smoking, intervention students were less
      likely to smoke regularly [OR = 0.51, 95% confidence interval (CI) = 0.36, 0.71]
      or to have smoked within the previous 30 days (OR = 0.69, 95% CI = 0.53, 0.91).
      CONCLUSION: The school-based adolescent harm minimization intervention appears to
      have been more effective than the abstinence-based social influences programme at
      reducing regular smoking.

PMID- 15847628
TI  - Nicotine analogues: a review of tobacco industry research interests.
AB  - AIMS: To explore the tobacco industry's interest and intentions driving its
      nicotine analogue research. METHODS: Review of internal tobacco industry
      documents regarding nicotine analogues released as part of the Master Settlement
      Agreement between the tobacco industry and US state governments in 1998.
      FINDINGS: The tobacco industry investigated nicotine analogues extensively. Four
      principal areas of interest are evident. First, research on tobacco products was
      directed towards greater understanding of nicotine pharmacology, how to screen
      for potential analogues and how to separate the central and peripheral effects of
      nicotine. Secondly, interest lay in the potential for analogues to replace
      nicotine in order to create more 'desirable' products and to circumvent
      anticipated nicotine regulation. Thirdly, interest lay in potential
      pharmaceutical applications for analogues such as treatments for neurological
      disorders. Finally, there was interest in the public relations potential of the
      therapeutic potential of analogues to reduce the demonization of nicotine, by
      allowing the industry to point to its beneficial uses. CONCLUSIONS: With tobacco
      product and nicotine regulation being increasingly advocated in tobacco control
      it is important to understand the industry's interests in the potential role of
      nicotine analogues. Initial interest included using analogues as a means to
      circumvent regulation, but evidence suggests these plans were discarded due to
      fear that this may have instigated regulation of tobacco products. Nicotine
      analogue research has led to potential therapeutic uses for Alzheimer's and
      Parkinson's diseases and alarmingly for the industry, to a potential vaccine to
      prevent nicotine addiction. RECOMMENDATIONS: Tobacco manufacturers should be
      obliged to declare all additives being used in tobacco products. Regulatory
      bodies should be aware that that there is a distinct possibility that the
      industry has discovered ways to circumvent future regulation of nicotine through
      the utilization of nicotine analogues. Any regulatory drafting should broaden the
      definition of nicotine in order to incorporate analogues into the scope of
      pharmacologically active substances being regulated.

PMID- 15847629
TI  - Do university students drink more hazardously than their non-student peers?

PMID- 15847630
TI  - The cannabis and psychosis connection questioned: a comment on Fergusson et al.
      2005.

PMID- 15847632
TI  - Establishment of a Moo Joose archive.

PMID- 15847639
TI  - The mitotic clock in skeletal muscle regeneration, disease and cell mediated gene
      therapy.
AB  - The regenerative capacity of skeletal muscle will depend on the number of
      available satellite cells and their proliferative capacity. We have measured both
      parameters in ageing, and have shown that although the proliferative capacity of
      satellite cells is decreasing during muscle growth, it then stabilizes in the
      adult, whereas the number of satellite cells decreases during ageing. We have
      also developed a model to evaluate the regenerative capacity of human satellite
      cells by implantation into regenerating muscles of immunodeficient mice. Using
      telomere measurements, we have shown that the proliferative capacity of satellite
      cells is dramatically decreased in muscle dystrophies, thus hampering the
      possibilities of autologous cell therapy. Immortalization by telomerase was
      unsuccessful, and we currently investigate the factors involved in cell cycle
      exits in human myoblasts. We have also observed that insulin-like growth factor-1
      (IGF-1), a factor known to provoke hypertrophy, does not increase the
      proliferative potential of satellite cells, which suggests that hypertrophy is
      provoked by increasing the number of satellite cells engaged in differentiation,
      thus possibly decreasing the compartment of reserve cells. We conclude that
      autologous cell therapy can be applied to specific targets when there is a source
      of satellite cells which is not yet exhausted. This is the case of Oculo
      Pharyngeal Muscular Dystrophy (OPMD), a late onset muscular dystrophy, and we
      participate to a clinical trial using autologous satellite cells isolated from
      muscles spared by the disease.

PMID- 15847640
TI  - Effects of spaceflight on postnatal development of arterial baroreceptor reflex
      in rats.
AB  - AIM: It has been reported that spaceflight attenuates the arterial baroreceptor
      reflex. As this reflex function changes dramatically during postnatal
      development, we hypothesized that space flight depresses the developmental
      changes of the reflex system. To test this hypothesis, we evaluated the
      baroreceptor reflex function in rats, which were exposed to a microgravity
      environment on a space shuttle 9-25 days after birth. METHODS: Baroreceptor
      reflex sensitivity and the afferent sensitivity were evaluated by measuring heart
      rate (HR) and aortic nerve activity (ANA) changes in response to an increase in
      mean arterial pressure (MBP) derived by phenylephrine injection (20-50 microg kg(
      1)) under urethane-anaesthesia. RESULTS: Baroreceptor reflex sensitivity (%
      change of HR/% change of MBP) was lower in the flight group (FLT: -0.19 +/- 0.04,
      n = 4) than either the asynchronous ground control group (AGC: -0.47 +/- 0.06, n
      = 6, P < 0.01) or the vivarium group (VIV: -0.41 +/- 0.07, n = 6, P < 0.05). This
      was similar to the differences of the afferent sensitivity (% change of ANA/%
      change of MBP) between FLT (2.07 +/- 0.30) and the control groups (AGC: 2.71 +/-
      0.22, n.s.; VIV: 3.00 +/- 0.32, P < 0.05). At the end of 30 days of recovery
      under normal gravity conditions, however, there were no significant group
      differences in these parameters. conclusion: These results suggest that the space
      environment attenuates the postnatal development of the arterial baroreceptor
      reflex function in rats, which may be partially because of a depression of the
      postnatal development of the baroreceptor afferents. These functional
      alterations, however, recover to their normal level on re-exposure to the Earth's
      gravity.

PMID- 15847641
TI  - Induction of myocardial connective tissue growth factor in pacing-induced heart
      failure in pigs.
AB  - AIMS: Connective tissue growth factor (CTGF) is a secreted, heparin-binding, and
      extracellular matrix associated protein shown to stimulate many of the cellular
      events underlying fibrosis. Previous investigations have revealed that myocardial
      CTGF is substantially induced in ischaemic heart failure, particularly in the
      ischaemic and peri-ischaemic region. The purpose of the present study was to
      investigate to what extent myocardial induction of CTGF is a general response to
      congestive heart failure (CHF) and to what extent CTGF is a decisive effector of
      fibrosis. METHODS: Experimental heart failure in pigs was induced by rapid pacing
      at 220-240 beats min(-1) for 3 weeks (CHF pigs; n = 12). RESULTS: The CHF pigs
      exhibited significant left ventricular (LV) dilatation, reduced contractility,
      and increased cardiac filling pressures. Northern blot analysis demonstrated that
      myocardial CTGF mRNA levels in CHF pigs were fivefold higher (P < 0.05) than
      those in control pigs (n = 10). Similar elevations of immunoreactive CTGF
      (sixfold; P < 0.05) were observed in myocardial tissue samples prepared for
      Western blot analysis. Immunohistochemical analysis of myocardial tissue sections
      revealed predominant expression in interstitial and perivascular fibroblasts and
      endothelial cells. Myocardial procollagen alpha1(I) mRNA levels were also
      significantly elevated (sixfold; P < 0.05) in CHF pigs compared with controls,
      whereas myocardial tissue contents of collagen were not statistically different
      between the groups. CONCLUSION: Induction of myocardial CTGF in heart failure is
      not just a response to ischaemia, but rather a general response to evolving heart
      failure. Yet, induction of myocardial CTGF was clearly not a sufficient effector
      of fibrosis.

PMID- 15847642
TI  - HSP20 phosphorylation and interstitial metabolites in hypoxia-induced dilation of
      swine coronary arteries.
AB  - OBJECTIVE: Hypoxia induces coronary artery dilation, but the responsible
      mechanism is largely unknown. Many stimuli induce arterial smooth muscle
      relaxation by reducing ser19-myosin regulatory light chain (MLC) phosphorylation.
      Other stimuli can induce smooth muscle relaxation without reductions in ser19-MLC
      phosphorylation. This form of relaxation has been termed force suppression and
      appears to be associated with heat shock protein 20 (HSP20) phosphorylation on
      ser16. We investigated whether hypoxia-induced sustained dilation in swine
      coronary arteries was promoted without ser19-MLC dephosphorylation and associated
      with ser16-HSP20 phosphorylation. Nitroglycerin vasodilation served as control.
      METHODS: In a pressure myograph, the tunica media of intact pre-contracted
      (PGF(2alpha); 10(-5) m) porcine coronary artery segments were cannulated using a
      microdialysis catheter. Diameter responses and interstitial lactate/pyruvate
      ratios were studied during 90 min hypoxia, hypoxia + reoxygenation (60 min),
      nitroglycerin (100 microm, 90 min), and nitroglycerin + wash-out (60 min). The
      arterial segments were snap-frozen and analysed for ser16-HSP20 phosphorylation
      and ser19-MLC phosphorylation. RESULTS: The normalized diameter responses to
      hypoxia (6.1 +/- 4.3%) and nitroglycerin (12.6 +/- 1.6%) were both significantly
      greater than normoxic control arteries (-10.5 +/- 1.8%, anova, P < 0.05). Ser16
      HSP20 phosphorylation was increased with hypoxia and nitroglycerin treatment and
      ser16-HSP20 phosphorylation correlated with changes in diameters (n = 29, r2 =
      0.64, P < 0.001). Ser19-MLC phosphorylation was not significantly altered by
      hypoxia. The lactate/pyruvate ratio was significantly increased in hypoxic
      arteries but did not correlate with diameters or ser16-HSP20 phosphorylation.
      CONCLUSION: Ser16-HSP20 phosphorylation is a potential regulator of hypoxia
      induced dilation in coronary arteries.

PMID- 15847643
TI  - Defective excitation-contraction coupling in hearts of rats with congestive heart
      failure.
AB  - AIM: We examined the cellular basis for depressed cardiac contractility in rats
      with congestive heart failure (CHF) secondary to myocardial infarction. METHODS:
      Six weeks after ligation of the left coronary artery, CHF was confirmed by
      haemodynamic measures and echocardiographic demonstration of reduced myocardial
      contractility in vivo. Papillary muscles from CHF animals developed less force
      than those from sham operated (SHAM) animals. Cell shortening was measured in
      isolated ventricular myocytes voltage-clamped with high resistance electrodes.
      Ca2+ transients were measured in fluo-4 loaded myocytes. RESULTS: Contractions
      triggered by depolarizing test steps from a post conditioning potential of -70 mV
      were significantly smaller and had significantly reduced velocity of shortening
      in CHF compared with SHAM myocytes. However, contractions initiated from -40 mV,
      were similar in amplitude and velocity of shortening in CHF and SHAM cells. L
      type Ca2+ current was not significantly different between CHF and SHAM cells,
      whether activated from -70 or -40 mV. Therefore, in SHAM cells, excitation
      contraction coupling exhibited higher gain when contractions were initiated from
      negative (-70 mV), as compared with depolarized potentials (-40 mV). However, in
      CHF myocytes, excitation-contraction coupling gain was selectively depressed with
      steps from -70 mV. This depression of gain in CHF was not accompanied by a
      significant reduction in sarcoplasmic reticulum Ca2+ content. Isoproterenol
      increased Ca2+ transients less in CHF than SHAM myocytes. CONCLUSION: In this
      post-infarction model of CHF, the contractile deficit was voltage dependent and
      the gain of excitation-contraction coupling was selectively depressed for
      contractions initiated negative to -40 mV.

PMID- 15847644
TI  - Effects of high-intensity intermittent swimming on PGC-1alpha protein expression
      in rat skeletal muscle.
AB  - AIM: The aim of the present investigation was to elucidate the effects of
      exercise intensity on exercise-induced expression of peroxisome proliferator
      activated receptor gamma coactivator-1alpha (PGC-1alpha) protein in rat skeletal
      muscle. METHODS: We measured PGC-1alpha content in the skeletal muscles of male
      Sprague-Dawley rats (age: 5-6 weeks old; body weight: 150-170 g) after a single
      session of high-intensity intermittent exercise (HIE) or low-intensity prolonged
      swimming exercise (LIE). During HIE, the rats swam for fourteen 20-s periods
      carrying a weight (14% of body weight), and the periods of swimming were
      separated by a 10-s pause. LIE rats swam with no load for 6 h in two 3-h
      sessions, separated by 45 min of rest. RESULTS: After HIE, the PGC-1alpha protein
      content in rat epitrochlearis muscle had increased by 126, 140 and 126% at 2, 6
      and 18 h, respectively, compared with that of the age-matched sedentary control
      rats' muscle. Immediately, 6 and 18-h after LIE, the PGC-1alpha protein content
      in the muscle was significantly elevated by 84, 95 and 67% respectively. The PGC
      1alpha protein content observed 6 h after HIE tended to be higher than that
      observed after LIE. However, there was no statistically significant difference
      between the two values (P = 0.12). CONCLUSION: The present investigation suggests
      that irrespective of the intensity of the exercise, PGC-1alpha protein content in
      rat skeletal muscle increases to a comparable level when stimuli induced by
      different protocols are saturated. Further, HIE is a potent stimulus for
      enhancing the expression of PGC-1alpha protein, which may induce mitochondrial
      biogenesis in exercise-activated skeletal muscle.

PMID- 15847645
TI  - Oestrogen influence on myogenic satellite cells following downhill running in
      male rats: a preliminary study.
AB  - AIM: This study examined the effect of oestrogen supplementation in rats on
      myogenic satellite cell quantities in type I and II muscles following eccentric
      exercise. METHODS: Gonad intact adult male rats divided into four groups,
      oestrogen supplemented (25 mg oestrogen pellet) control (EC), oestrogen
      supplemented, exercised (EE), sham (no oestrogen) control (SC) and sham,
      exercised (SE). After 1 week of oestrogen exposure the EE and SE animals
      performed 90 min of intermittent downhill running (5 min running/2 min rest @
      13.5 degrees incline and 17 m min(-1) speed). Seventy-two hours later exercised
      (EE and SE) and control (EC and SC) animals were killed and blood samples taken
      and soleus and white (superficial) vastus muscles surgically removed.
      Histochemical sections of soleus and white vastus muscles were examined for
      myogenic satellite cell content by use of Pax7 antibody and for neutrophil
      content by use of haematoxylin and eosin (H and E) staining procedures. RESULTS:
      Downhill running resulted in significant elevations in satellite cells and
      neutrophils detected in both soleus and white vastus muscle samples (P < 0.01).
      Interestingly, oestrogen supplementation resulted in significantly greater (P <
      0.01) post-exercise elevations in satellite cells detected in both soleus and
      white vastus muscle samples compared with sham (no oestrogen) rats. Increases in
      neutrophils were significantly (P < 0.05) attenuated in oestrogen supplemented
      rats relative to sham in soleus but not in white vastus muscles. CONCLUSIONS:
      Oestrogen supplementation in male rats may have accentuated the 72 h post
      downhill running increase in Pax7 detected myogenic satellite cell number in both
      soleus and white vastus muscles relative to unsupplemented rats. The mechanisms
      and physiological consequences of this effect are yet to be determined.

PMID- 15847646
TI  - Abnormal renal structural alterations during the development of diabetes mellitus
      in Otsuka Long-Evans Tokushima Fatty rats.
AB  - AIM: The aim of this study was to investigate the renal structural properties in
      diabetic nephropathy. METHODS: Flow-pressure and pressure-glomerular filtration
      rate (GFR) relationships were determined for maximally vasodilated kidneys at 10
      (pre-diabetic stage) and 42 weeks of age (diabetic stage) in Otsuka Long-Evans
      Tokushima Fatty rats (OLETF), an animal model of type 2 diabetes mellitus, using
      age-matched Long-Evans Tokushima Otsuka rats (LETO) as non-diabetic controls (n =
      9 of each age for each strain). Kidneys were then perfusion-fixed for
      histological analysis. RESULTS: At 10 weeks of age, the slope of flow-pressure
      relationship (minimal renal vascular resistance, reflecting overall luminal
      dimensions of preglomerular and postglomerular vasculature) was steeper in OLETF
      than in LETO. In contrast, the threshold pressure for beginning filtration
      (preglomerular-to-postglomerular vascular resistance ratio) at pressure-GFR
      relationship did not differ between the two strains; however, the slope of the
      relationship (glomerular filtration capacity) was lower in OLETF than in LETO.
      Thus, in the kidneys of 10-week-old OLETF rats, vascular narrowing and impaired
      glomerular filtration capacity already existed with no abnormalities in
      preglomerular-to-postglomerular vascular resistance ratio. From the age of 10-42
      weeks, the following results were obtained: (1) Minimal renal vascular resistance
      decreased in both strains, but it diminished markedly in OLETF. (2) The pressure
      for beginning filtration increased in LETO, but remained unchanged in OLETF. (3)
      Glomerular filtration capacity decreased to the similar extent in both strains.
      (4) Histologically, the vascular lumen and wall thickness increased in the
      interlobular arteries of both strains. However, vascular luminal widening was
      more pronounced in OLETF, resulting in the reduction in wall to lumen ratio. (5)
      Glomerular injuries and increased blood pressure occurred only in OLETF.
      CONCLUSION: In conclusion, during progression from the prediabetic to diabetic
      stage of OLETF, the pre-existing vascular narrowing was markedly attenuated
      without the concomitant increase in preglomerular-to-postglomerular vascular
      resistance ratio. Combined with increased blood pressure, these renal structural
      alterations could lead to the elevation of intraglomerular pressure in OLETF.

PMID- 15847647
TI  - Diastolic performance in the aged heart.

PMID- 15847649
TI  - Transfusion medicine illustrated. Volume-reduced apheresis platelets.

PMID- 15847650
TI  - Goodbye to agglutination and all that?

PMID- 15847651
TI  - Microarray-based genotyping for blood groups: comparison of gene array and 5'
      nuclease assay techniques with human platelet antigen as a model.
AB  - BACKGROUND: Most blood group alloantigens specific for red cells and platelets
      (PLTs) are based on single-nucleotide polymorphisms (SNPs) in genes encoding
      relevant membrane proteins. STUDY DESIGN AND METHODS: By use of five human PLT
      antigen (HPA) systems as a model, the suitability of a fourth-generation
      microarray technique for SNP typing was investigated. The results of the former
      were compared with those of a parallel developed third-generation technique
      (TaqMan assay, Applied Biosystems). Both techniques were validated by use of a
      unique panel of 71 blinded DNA samples containing at least 15 aa, bb, and ab
      genotypes for the HPA-1, -2, -3, -5, and-15 systems. RESULTS: Unambiguous and
      concordant results were obtained with both techniques for all samples.
      CONCLUSION: The data presented here validate the use of microarray for large
      scale SNP typing for clinically relevant blood group alloantigens.

PMID- 15847652
TI  - High-throughput multiplex single-nucleotide polymorphism analysis for red cell
      and platelet antigen genotypes.
AB  - BACKGROUND: Transfusion recipients who become alloimmunized to red cell or
      platelet (PLT) antigens require antigen-negative blood to limit adverse
      transfusion reactions. Blood collection facilities use regulated and unregulated
      antibodies to phenotype blood, the cost of which can be prohibitive depending on
      the antisera and demand. An alternative strategy is to screen blood for these
      antigens with genomic DNA and the associated single-nucleotide polymorphisms
      (SNPs). STUDY DESIGN AND METHODS: A multiplex polymerase chain reaction (PCR)
      oligonucleotide extension assay was developed with genomic DNA and a SNP
      genotyping platform (GenomeLab SNPstream, Beckman Coulter) to identify SNPs
      related to D, C/c, E, S/s, K/k, Kp(a/b), Fy(a/b), FY0 (-33 promoter silencing
      polymorphism), Jk(a/b), Di(a/b), and human PLT antigen (HPA)-1a/1b. A total of
      372 samples were analyzed for 12 SNPs. The genotypes were compared to the blood
      group and PLT antigen phenotypes. RESULTS: Individual sample results varied from
      98 to 100 percent for 11 of 12 SNPs. D was correctly identified in 292 of 296
      (98.6%) D+ donors. The RHCE exon 5 E/e SNP analysis had the lowest concordance
      (89.5%). Thirty-three R(1)R(1) and 1 r"r were correctly identified. PCR
      restriction fragment length polymorphism (RFLP) on selected samples confirmed the
      presence of the FY0 silencing polymorphism in nine donors. Homozygous HPA-1b/1b
      was identified in four donors, which was confirmed by PCR-RFLP (n = 4) and anti
      HPA-1a serology (n = 2). The two HPA-1a-negative donors were recruited into the
      plateletpheresis program. CONCLUSION: The platform has the capacity to genotype
      thousands of samples per day. The suite of SNPs provides genotype data for all
      blood donors within 36 hours of the start of testing.

PMID- 15847653
TI  - Rapid genotyping of blood group antigens by multiplex polymerase chain reaction
      and DNA microarray hybridization.
AB  - BACKGROUND: In the Netherlands, 500,000 blood donors are active. Blood of all
      donors is currently typed serologically for ABO, the Rh phenotype, and K. Only a
      subset of donors is typed twice for a larger set of red cell (RBC) and/or
      platelet (PLT) antigens. To increase the direct availability of typed RBCs and
      PLTs, a high-throughput technique is being developed to genotype the whole donor
      cohort for all clinically relevant RBC and PLT antigens. STUDY DESIGN AND
      METHODS: A multiplex polymerase chain reaction was developed to both amplify and
      fluorescently label 19 gene fragments of RBC and PLT antigens in one reaction. To
      test the setup of the genotyping method by microarray, a pilot study with human
      PLT antigen (HPA)-typed donor samples was performed. On each slide, 12 arrays are
      present containing 20 probes per PLT antigen system (28 for HPA-3). The allele
      specific oligohybridization method was used to discriminate between two different
      alleles. RESULTS: Two blinded panels encompassing 94 donors were genotyped for
      HPA-1 through -5 and -15; no discrepancies were found compared to their serologic
      typing (HPA-1, -2, -3, -4, and -5) and genotyping (HPA-15; TaqMan, Applied
      Biosystems). CONCLUSION: This study shows that the HPA microarray provides a
      reliable and fast genotyping procedure. With further development an automated
      throughput for complete typing of large donor cohorts can be obtained.

PMID- 15847654
TI  - A flexible array format for large-scale, rapid blood group DNA typing.
AB  - BACKGROUND: Typing for blood group antigens is currently performed by
      hemagglutination. The necessary reagents are becoming costly and limited in
      availability, and the methods are labor-intensive. The purpose of this study was
      to determine the feasibility of the use of large-scale DNA analysis in a
      microarray as a substitute for blood group typing. STUDY DESIGN AND METHODS: DNA,
      extracted from blood samples that had been phenotyped for some of the red blood
      cell antigens, was analyzed for selected blood group alleles by bead array
      (BeadChip, (BioArray Solutions Ltd., Warren, NJ) Illumina) [corrected] and by
      manual polymerase chain reaction (PCR)-based assays. Selected alleles were
      identified by enzyme-mediated elongation of probes, which were on color-encoded
      beads assembled into arrays on silicon chips. The performance of a prototype
      BeadChip (BioArray Solutions Ltd., Warren, NJ) [corrected] (BLOOD-1) containing
      single-nucleotide polymorphisms (SNPs) for FYA/B, FY-GATA, DOA/B, COA/B, LWA/B,
      DIA/B, and SC1/SC2 was verified with DNA from serologically characterized donors.
      It was then used to analyze more than 400 samples of partially defined phenotype.
      Samples from Chinese, Ashkenazi, and Thai donors (total n = 227) were tested with
      BLOOD-1. An expanded BeadChip (BioArray Solutions Ltd., Warren, NJ) [corrected]
      with a total of 18 SNPs (36 alleles; SNPs in BLOOD-1 and M/N, S/s, Lu(a)/Lu(b),
      K/k, FY265[for the Fy(X) polymorphism], Jk(a)/Jk(b), DO323[for Hy], DO350[for
      Jo(a)], and HgbS) was then evaluated with a subset of previously tested samples
      from Chinese, Ashkenazi, and New York blood donors (127) and an additional set of
      samples from Israeli donors (total n = 188). RESULTS: Results obtained by
      BeadChip (BioArray Solutions Ltd., Warren, NJ) [corrected] analysis were
      concordant with those obtained with the manual PCR-restriction fragment length
      polymorphism, allele-specific PCR, and hemagglutination assays. The frequencies
      of the alleles in the samples from different ethnic panels were within the
      expected ranges; however, two new DO alleles were discovered. CONCLUSION: It has
      been shown that microarray technology can be used to type DNA and detect new
      alleles in donor cohorts.

PMID- 15847655
TI  - Detection of weak D with a fully automated solid-phase red cell adherence system.
AB  - BACKGROUND: Microplate agglutination methods (MAMs) and column agglutination
      technology are widely employed for red cell typing and can be automated. Some
      tests, however, such as detection of weak D, require manual testing. The
      possibility of detecting weak D by a solid-phase RBC adherence (SPRCA) test was
      studied in a fully automated system. STUDY DESIGN AND METHODS: The results of
      2609 blood samples, characterized as being D- or with a incomplete agglutination
      reaction, were analyzed for the presence of the weak D phenotype. The 2609
      samples were tested by a weak D tube test (antiglobulin method) and a weak D-test
      with the new SPRCA method. When weak D was detected, which D epitope was involved
      and whether it was associated with a partial D phenotype were determined.
      RESULTS: Weak D was detected in 60 (2.3%) of the 2609 samples. The 60 samples
      that were weak D by the tube test were also weak D+ with the new automated SPRCA
      test. The sensitivity and specificity for the new weak D typing method were 100
      percent, when compared with the standard weak D manual test. CONCLUSIONS: These
      results support the possibility of performing weak D detection with a SPRCA fully
      automated system. These preliminary results are encouraging, showing good
      sensitivity and specificity of the test. Detection of weak D will permit full
      automation of blood typing.

PMID- 15847656
TI  - Use of polyethylene glycol for performing autologous adsorptions.
AB  - BACKGROUND: Our reference adsorption procedure is to autoadsorb serum with ZZAP
      pretreated patients' red cells (RBCs), although it is time-consuming. The aim of
      this study was to evaluate the use of polyethylene glycol (PEG) for performing
      autologous adsorption procedures without pretreatment of patients' RBCs. STUDY
      DESIGN AND METHODS: Equal volumes of patient's plasma, patient's RBCs, and PEG
      were mixed. This mixture was incubated for 15 minutes at 37 degrees C, and the
      adsorbed plasma-PEG mixture was immediately harvested to proceed to the
      antiglobulin test with anti-immunoglobulin G. The ZZAP-adsorption procedure was
      performed in our reference laboratory. RESULTS: Thirty-one samples were detected
      with warm autoantibodies in pretransfusion testing. A total number of 58
      autologous adsorption procedures were performed with PEG in 870 minutes (mean, 28
      min) and alloantibodies were detected in 4 (13%) cases (anti-E in 2 cases and
      anti-E + K in 2 cases). Our reference laboratory performed a total number of 61
      adsorption procedures with ZZAP in 3660 minutes (mean, 118 min) and detected the
      same alloantibodies specificities. CONCLUSION: The PEG autologous adsorption
      procedure is an efficient method of enhancing autoantibody adsorption and
      alloantibody detection and decreasing the labor-intensive testing required by the
      presence of serum warm autoantibodies in pretransfusion samples.

PMID- 15847657
TI  - Tetragametic chimerism detected in a healthy woman with mixed-field agglutination
      reactions in ABO blood grouping.
AB  - BACKGROUND: The case of a healthy woman with serologic blood group AB and her
      biologic father showing blood group O was investigated. Further analysis,
      including blood, buccal swabs, and nail clippings, revealed a tetragametic
      chimerism. STUDY DESIGN AND METHODS: Blood grouping was performed with standard
      gel centrifugation test cards, ABO genotyping by sequence-specific primers (SSPs)
      and sequence-based typing, and HLA Class I and II typing by standard NIH
      cytotoxicity testing and SSP. Additionally, short-tandem-repeat (STR) and
      variable-number tandem-repeat (VNTR) typing was performed on blood, nail
      clippings, and buccal swab samples. The karyotype was analyzed by G-banded
      chromosomes. RESULTS: The proposita's RBCs were typed AB with a mixed-field
      agglutination whereas in molecular typing A, B, and O alleles were found. One
      paternal and two maternal haplotypes were determined by use of HLA typing.
      Interestingly, both paternal alleles were detected in 4 of 23 tested STR and VNTR
      loci only, with whole blood, nail clippings, and buccal swabs. The karyotype was
      identified as 46XX. The family members including the proposita's healthy twin
      children displayed no abnormal findings in tests performed. CONCLUSION: By
      investigation of DNA polymorphisms, it was possible to determine a rare case of
      tetragametic chimerism being the result of double parental contribution of
      nuclei.

PMID- 15847658
TI  - Oxaliplatin-induced immune pancytopenia.
AB  - BACKGROUND: Oxaliplatin, a third-generation platinum compound, has been
      implicated in isolated cases of immune hemolytic anemia and/or immune
      thrombocytopenia. The first case of severe immune pancytopenia related to
      oxaliplatin is described. PATIENT AND METHODS: A 79-year-old woman with
      colorectal cancer was initially treated with 5-fluorouracil and she later
      received oxaliplatin and leucovorin every 2 to 4 weeks. During the 15th and 17th
      cycles of chemotherapy she developed thrombocytopenia, hemolysis, and
      neutropenia. No problems occurred during the 16th cycle without oxaliplatin.
      Serologic testing including detection of drug-dependent antibodies and
      autoantibodies was performed with standard techniques. RESULTS: Serologic
      findings included a positive immunoglobulin G direct antiglobulin test;
      nonreactive red blood cell (RBC) eluates; platelet (PLT)-bound antibodies to
      glycophorin (GP) IIb-IIIa, GPIb-IX, and GPIa-IIa; and oxaliplatin-dependent
      antibodies to PLTs, RBCs, and neutrophils. CONCLUSION: Oxaliplatin may lead to
      the production of ddabs to RBCs, PLTs, and neutrophils. Thus the risk of immune
      cytopenias should always be considered in patients treated with oxaliplatin.

PMID- 15847659
TI  - Monoclonal antibody B2, a marker of neuroendocrine sympathoadrenal precursors,
      recognizes the Luke (LKE) antigen.
AB  - BACKGROUND: Blood group antigens are physiologically important differentiation
      markers in embryogenesis and development. Monoclonal antibody (MoAb) B2
      recognizes a transient antigen expressed on late sympathoadrenal neuroendocrine
      precursors and early sympathetic neuroblasts. It has been suggested that MoAb B2
      may recognize a globo-series glycosphingolipid (GSL) related to the P blood group
      family. STUDY DESIGN AND METHODS: MoAb B2 and two anti-LKE MoAbs, MC813-70 and
      RM1, were screened against a panel of GSL standards and isolated red blood cell
      (RBC) GSLs by high-performance thin layer chromatography (HPTLC) immunostaining.
      The ability of all three MoAbs to bind intact RBCs and two LKE+ renal cell
      carcinoma cell lines (A498, ACHN) were examined by flow cytometry and
      hemagglutination. RESULTS: MoAbs B2, MC813-70, and RM1 all specifically
      recognized monosialogalactosylgloboside (MSGG) on HPTLC immunostaining. Only MoAb
      MC813-70 bound intact RBC by flow cytometry and hemagglutination. Differential
      staining was observed between the three antibodies and two renal cell carcinoma
      cell lines. CONCLUSION: MoAb B2 recognizes MSGG or LKE antigen, suggesting that
      LKE may play a role in neuroendocrine differentiation from neural crest cells.
      Although MoAb B2 is not suitable for RBC phenotyping, it may be a useful
      immunologic reagent for the identification of human embryonic stem cells and
      renal cell and embryonic carcinoma.

PMID- 15847660
TI  - The development of a quantitative enzyme-linked immunosorbent assay to detect
      human platelet factor 4.
AB  - BACKGROUND: Platelet factor 4 (PF4) is a marker for in vitro and in vivo tests of
      platelet (PLT) activation and alpha-granule secretion. PF4 is also a major CXC
      cytokine released during storage. Cytokines released during PLT storage are a
      potential cause of nonhemolytic transfusion reactions. Quantitative measurement
      of PF4 requires an assay that is both reliable and sensitive. To achieve this
      goal, a sensitive, cost-effective, sandwich enzyme-linked immunosorbent assay
      (ELISA) was developed with commercially available antibodies to human PF4. STUDY
      DESIGN AND METHODS: An ELISA was developed for measuring PF4 from whole human
      PLTs or secreted from activated PLTs. Optimal concentrations of capture antibody,
      detection antibody, and enzyme-conjugate were determined with serial twofold
      dilutions of recombinant PF4. This assay was used to determine the ideal sample
      dilutions needed for reliable quantitation of PF4 in releasates or from whole PLT
      extracts. RESULTS: Serial dilutions of recombinant PF4 resulted in a sigmoid
      titration curve with a maximal sensitivity of 10 pg and a dynamic quantitative
      range from 100 to 2500 pg. This ELISA was used to measure secretion from
      permeabilized PLTs stimulated with free calcium. In a secretion experiment with
      2.5 x 10|*bsup*|8|*esup*| PLTs per mL, samples required a 1:10-fold dilution to
      reliably evaluate alpha-granule release. CONCLUSION: The parameters described
      yield an ELISA method with low background and high sensitivity over a range of
      PF4 concentrations. Using the commercial reagents described makes this assay cost
      effective and therefore suitable for analyzing multiple samples in the research
      setting.

PMID- 15847661
TI  - Molecular basis for para-Bombay phenotypes in Chinese persons, including a novel
      nonfunctional FUT1 allele.
AB  - BACKGROUND: The para-Bombay phenotype is characterized by H-deficient or H
      partially deficient red blood cells (RBCs) in persons who secrete ABH antigens in
      their saliva. The studies that determined the genotypes for two Chinese
      individuals with the para-Bombay phenotype are described. STUDY DESIGN AND
      METHODS: RBC phenotypes were characterized by conventional serologic methods.
      Exons 6 and 7 of the ABO gene were amplified, as well as the entire coding region
      for FUT1 and FUT2, with four independence polymerase chain reactions (PCRs) from
      genomic DNA. PCR products were excised, purified from agarose gels, and sequenced
      directly. Mutations of FUT1 were identified by TOPO cloning sequencing. RESULTS:
      For both individuals, RBC ABO genotypes correlated with ABH substances in their
      saliva. One individual (a patient) had two heterozygous mutations of FUT1 by
      direct DNA sequencing, namely, a C-->T heterozygous mutation at position
      293(C293T) and AG heterozygous deletion (CAGAGAG-->CAGAG) at position 547 to 552.
      These two mutations were confirmed to be compound heterozygotes; that is, each
      mutation was determined to be on a separate homologous chromosome by TOPO cloning
      sequencing. The FUT2 genotype was Se(357)Se(357). The other individual (a blood
      donor) had an AG deletion at position 547 to 552 homozygous allele in FUT1. The
      FUT2 genotype was Se(357)Se(357,385). C293T mutation can cause Thr/Met at amino
      acid position 98. AG deletion at position 547 to 552 caused a reading frameshift
      and a premature stop codon. CONCLUSION: A novel nonfunctional FUT1 allele C293T
      was identified in a person with the para-Bombay phenotype. This rare H-deficient
      phenotype may result from different nonfunctional alleles.

PMID- 15847662
TI  - Detection of bacteria in platelet concentrates: comparison of broad-range real
      time 16S rDNA polymerase chain reaction and automated culturing.
AB  - BACKGROUND: Based on real-time polymerase chain reaction (PCR) technology, a
      broad-range 16S rDNA assay was validated and its performance was compared to that
      of an automated culture system to determine its usefulness for rapid routine
      screening of platelet concentrates (PCs). STUDY DESIGN AND METHODS: The presence
      of bacteria in pooled PCs was routinely assessed in an automated culturing system
      (BacT/ALERT, bioMerieux). The PCR assay was performed with DNA extracted from the
      same samples as used for culturing. DNA extraction was performed with a automated
      extraction system (MagNA Pure, Roche Diagnostics). PCR amplification was
      performed with a set of universal primers and probe targeting eubacterial 16S
      rDNA. RESULTS: A total of 2146 PCs were tested. Eighteen (0.83%) samples were
      found to be contaminated. These samples were positive for the presence of
      bacteria by both methods. All contaminants were identified as bacteria belonging
      to the common human skin flora. These included Propionibacterium spp. (n = 7),
      Staphylococcus spp. (n = 6), Bacillus spp. (n = 2), Micrococcus spp. (n = 2), and
      Peptostreptococcus spp. (n = 1). Estimation of the bacterial load in PCs by real
      time PCR showed that the initial levels of contamination varied between 13.6 and
      9 x 10(4) colony-forming unit equivalents per PCR procedure. CONCLUSIONS:
      Compared to culture in the BacT/ALERT system, the PCR assay had a sensitivity of
      100 percent and a specificity of 100 percent. This real-time PCR assay has a much
      shorter turnaround time of 4 hours, which offers the possibility to test and
      obtain results on PCs before release or the day they are transfused. This would
      permit the withdrawal of contaminated PCs before transfusion.

PMID- 15847663
TI  - Clinical experience with the delivery of thawed and washed autologous blood
      cells, with an automated closed fluid management device: CytoMate.
AB  - BACKGROUND: Washing out of thawed autologous grafts, before reinfusion in poor
      prognosis cancer patients who undergo high-dose chemotherapy, is desirable. The
      procedure allows for the reduction of infused dimethyl sulfoxide (DMSO)
      quantities and the performance of biologic controls on the infused cell product.
      STUDY DESIGN AND METHODS: Three-hundred four patients were treated with
      intensified chemotherapy and autologous transplantation at a single institution.
      Fifty-four of them received washed cell products, because three or more bags were
      to be reinfused. The recently available, closed, automated, and current good
      manufacturing practice-compliant device (CytoMate, Baxter Oncology) was used for
      this purpose. RESULTS: The performances of the device were similar to previously
      reported results, with greater than 75 percent CD34+ cell recovery. Neutrophil
      and platelet (PLT) recoveries were similar in the group of patients receiving
      washed cells and in the group of patients for whom cell products were
      extemporaneously thawed at the bedside. Adverse events that are typically
      reported after DMSO infusion were significantly less frequent and less severe in
      patients who received washed cells. Finally, the nurse staff on the transplant
      ward reported a decreased workload and more satisfactory procedure when infusing
      washed cell products. CONCLUSION: The CytoMate device allows for a significant
      reduction in DMSO infusion, with a diminished frequency and severity of immediate
      side effects and does not compromise neutrophil or PLT engraftment.

PMID- 15847664
TI  - Automated preparation of platelet concentrates from pooled buffy coats: in vitro
      studies and experiences with the OrbiSac system.
AB  - BACKGROUND: The aim was to evaluate platelet concentrates (PCs) prepared by the
      automated OrbiSac system, from pooled buffy coats (BCs) stored in a platelet
      (PLT) additive solution. STUDY DESIGN AND METHODS: Experiment 1 was a paired in
      vitro study of PCs (from six BCs), prepared by automated and manual procedures.
      Experiments 2 and 3 evaluated PCs from OrbiSac (from six BCs); Experiment 3
      included selection of BCs based on donor data. Experiment 4 was a paired in vitro
      study of PCs (from six BCs) with an integrated white blood cell (WBC) filter and
      two different storage containers. Experiment 5 evaluated PCs (from six BCs) from
      the OrbiSac with an integrated WBC filter. Experiment 6 was similar to Experiment
      5 with computer-selected pools of 5 BCs. The in vitro studies evaluated the
      effects of 7-day storage of PLTs regarding PLT metabolism and disintegration.
      RESULTS: Experiments 1 and 4 had similar in vitro results. In Experiment 2, PLT
      content was 370 x 10(9) +/- 70 x 10(9) per PC and recovery from BCs was 76 +/- 6
      percent. In Experiment 3, the PLT content was 380 x 10(9) +/- 50 x 10(9) per PC
      and variation was reduced compared with randomly pooled BCs. In Experiment 5,
      increased PLT content was found (420 x 10(9) +/- 70 x 10(9) per PC and recovery
      from BCs of 80 +/- 5%). In Experiment 6, five rather than six BCs gave 340 x
      10(9) +/- 60 x 10(9) PLTs per PC and recovery was 79 +/- 5 percent. CONCLUSION:
      These in vitro studies suggest that the OrbiSac technique is equivalent to the
      standard manual method regarding the PLT in vitro characteristics during storage
      for 7 days. The results of standardizing the PLT count in PCs by selecting the
      BCs pools on the basis of the blood donor PLT concentration were encouraging.

PMID- 15847665
TI  - Use of a flexible thiopyrylium photosensitizer and competitive inhibitor for
      pathogen reduction of viruses and bacteria with retention of red cell storage
      properties.
AB  - BACKGROUND: Progress in developing photochemical methods for pathogen reduction
      of red blood cells (RBCs) has been hampered by hemolysis. A flexible, nucleic
      acid-intercalating thiopyrylium (TP) dye that is only photochemically active in
      the bound state and a competitive inhibitor of RBC membrane binding, dipyridamole
      (DP), was used to reduce photoinduced hemolysis stemming from free- and membrane
      bound dye. STUDY DESIGN AND METHODS: Oxygenated leukodepleted 20% hct RBC
      suspensions were deliberately inoculated with virus or bacteria, incubated with
      200 micromol per L DP and less than or equal to 100 micromol per L TP,
      illuminated with 1.1 J/cm(2) of red light, and titered. RBC suspensions
      containing 200 micromol per L DP and 160 micromol per L TP were identically
      phototreated, concentrated to 45% hct, and assayed for RBC storage properties.
      RESULTS: In RBC suspensions containing DP, TP photoinactivated vesicular
      stomatitis virus, pseudorabies virus, duck hepatitis B virus, bovine virus
      diarrhea virus, extracellular human immunodeficiency virus (HIV) to the limit of
      detection and 6.2 log intracellular HIV. More than 5 log inactivation of 6
      bacterial species was demonstrated. DP prevented approximately 30% of TP binding
      to RBCs. Phototreated RBCs that were subsequently stored for 42 days exhibited
      acceptable levels of hemolysis, morphology scores, extracellular pH, ATP, glucose
      utilization rates, and lactate production. Treated samples exhibited
      substantially increased potassium efflux compared to controls. CONCLUSION: Use of
      TP photosensitizer and DP enables significant levels of pathogen reduction while
      retaining most, but not all RBC properties during 42 day storage.

PMID- 15847666
TI  - Platelet alloimmunization after long-term red cell transfusion in transfusion
      dependent thalassemia patients.
AB  - BACKGROUND: The platelet (PLT) alloimminization status after long-term red cell
      (RBC) transfusion in thalassemia patients was investigated, including antibodies
      against HLA antigens and PLT-specific glycoprotein antigens. STUDY DESIGN AND
      METHODS: Blood samples from a total of 60 thalassemia patients who routinely
      received washed RBCs were tested for the presence of HLA antibodies and PLT
      specific glycoprotein antibodies with a commercial enzyme immunoassay kit. All
      patients were rescreened at a follow-up period of 12 to 15 months. RESULTS: At
      the first year of study, 19 (31%) patients had HLA antibodies, 13 (22%) had HLA
      antibodies and PLT-specific antibodies, and 1 (2%) had PLT-specific antibodies.
      One patient showed weak reactive PLT autoantibody. The follow-up study showed
      that 7 patients developed HLA antibodies, whereas 1 patient lost HLA antibody
      activity. Nine patients developed new PLT-specific antibodies, yet 12 patients
      lost at least one of their PLT-specific antibodies. CONCLUSION: Long-term RBC
      transfusions can induce PLT alloimmunization, both to HLA antigens and to PLT
      specific antigens. The residual PLTs and white blood cells in RBC components
      could be the sources of immunization. In our thalassemia patients, HLA antibodies
      likely sustain longer than PLT-specific antibodies.

PMID- 15847667
TI  - Reticulated platelets: a reliable measure to reduce prophylactic platelet
      transfusions after intensive chemotherapy.
AB  - BACKGROUND: Reticulated platelets (RPs) are the youngest circulating platelets
      (PLTs). The aim of our study was to predict PLT recovery with RP percentage (RP%)
      and therefore to identify PLT transfusions that could be avoided after autologous
      peripheral blood progenitor cell (PBPC) transplantation. STUDY DESIGN AND
      METHODS: With a whole-blood dual-labeling flow cytometric method, RP% was
      prospectively assessed in 47 patients who received myeloablative chemotherapy
      followed by autologous PBPC transplantation. Retrospective analysis of RP
      evolution identified three time points: nadir of the RP% (NRP), imminent PLT
      recovery (IPR) corresponding to an RP% of greater than 7 percent, and PLT
      transfusion autonomy (PTA). RESULTS: Median occurrences of NRP, IPR, and PTA were
      on Days +5, +8, and +12 after transplantation, respectively. The RP% value at NRP
      (4%) was significantly lower compared to the IPR (15%) and PTA (14%). Thirty
      patients (64%) achieved PTA within 4 days after IPR. On Day +8, if RP% was
      greater than 7 percent, positive and negative predictive values for PTA within 4
      days, specificity, and sensitivity were 79, 63, 66, and 76 percent, respectively.
      Fever between IPR and PTA was the only factor found to negatively influence PLT
      recovery (p = 0.02). All patients required at least one PLT transfusion. Among
      patients with rapid PLT recovery (IPR-PTA interval < 4 days; n = 30), half of
      them received one PLT transfusion after RP increase, which could be avoided.
      CONCLUSION: These encouraging results may allow us to reduce the prophylactic PLT
      transfusion according to patients RP% increase.

PMID- 15847668
TI  - The value of pH as a quality control indicator for apheresis platelets.
AB  - BACKGROUND: Standards and regulations require measurement of pH as an apheresis
      platelet (PLT) component quality monitor. The usefulness of this quality control
      (QC) measure was investigated. STUDY DESIGN AND METHODS: QC data were
      retrospectively reviewed for apheresis PLTs collected over 4.5 years. Three
      collection devices were used, the Amicus (Baxter), the CS-3000 Plus (Baxter), and
      the MCS+ LN9000 (Haemonetics). Each month, four components from each instrument
      were sampled. PLT counts and component volume were measured immediately after
      collection, and pH, after 5 days of storage. RESULTS: A total of 668 products
      were studied. pH decreased as PLT concentration increased (r(2) = 0.129, p <
      0.001) and as component volume decreased (r(2) = 0.086, p = 0.02). PLT
      concentration and volume, however, were poor predictors of a low pH. Apheresis
      instrument type affected pH. The 216 components collected with use of the CS-3000
      device had a lower pH than components from the other two instruments. Only 13
      components had a pH value less than the acceptable level of 6.2, 12 of which were
      collected with the CS-3000. CONCLUSIONS: For newer-model blood cell separators,
      pH measurements do not provide information that might identify a manufacturing
      problem. Because factors that influence pH are controlled or monitored for each
      component, evaluation of pH on a sample group provides an indication of the
      quality of specific component only, rather than an effective monitor of the
      quality of the manufacturing process.

PMID- 15847669
TI  - After major ABO-mismatched allogeneic hematopoietic progenitor cell
      transplantation, erythroid engraftment occurs later in patients with donor blood
      group A than donor blood group B.
AB  - BACKGROUND: Isohemagglutinins directed against the donor blood group frequently
      delay erythroid engraftment after major ABO-mismatched allogeneic hematopoietic
      progenitor cell transplantation (HPCT). Graft-versus-host reactions are capable
      of accelerating the clearance of isohemagglutinins. Whether immunogenicity of the
      A- and B-antigen is important in this process is unknown. PATIENTS AND METHODS:
      Data of 807 patients from three centers were screened for patients with major or
      bidirectionally ABO-mismatched donors. Clinical data and red blood cell (RBC)
      transfusion support were analyzed retrospectively. RESULTS: A total of 158
      patients with major or bidirectionally mismatched donors were identified. After
      major mismatched HPCT, patients with anti-A directed against the donor blood
      group required RBC transfusion support for a median of 109 days (range, 0-324
      days) compared to 21 days (range, 2-98 days) for patients with anti-B directed
      against donor blood group (log-rank test, p = 0.0001). Other risk factors
      associated with prolonged RBC transfusion support in univariate analysis were age
      (p = 0.024), cytomegalovirus infection (p = 0.016), hemolytic anemia (p = 0.027),
      and chronic bleeding disorders (p = 0.038). The independent influence of donor
      blood group and recipient age were confirmed in a multivariate analysis.
      CONCLUSION: These results indicate that the immunogenicity of the ABO antigen
      plays an important role for the kinetics of erythroid engraftment after ABO
      mismatched HPCT.

PMID- 15847670
TI  - Frequently used plateletpheresis techniques result in variable target yields and
      platelet recruitment of donors.
AB  - BACKGROUND: Standard plateletpheresis techniques and effects on platelet (PLT)
      donors were investigated to provide an informative basis for advancement of
      apheresis software. STUDY DESIGN AND METHODS: Three paired groups with 33 male
      and 22 female blood donors were prospectively investigated by analyzing blood
      counts of donors and products. Four apheresis platforms, the COBE Spectra LRS and
      the Trima v4 (Gambro BCT) and the AS.TEC204 and the COM.TEC (Fresenius Hemocare),
      were compared. Deviations of the collected from programmed PLT targets and donor
      PLT recruitment were calculated for single-unit PLT concentrates (SU-PCs; 3 x
      10(11) PLTs) and double-unit PLT concentrates (DU-PCs; 6 x 10(11) PLTs). RESULTS:
      Regarding SU-PCs, the productivity of the COM.TEC machine was superior to the
      AS.TEC204 machine, because of shorter processing time (54 min vs. 67 min) and
      higher yields (2.90 x 10(11) PLTs vs. 2.75 x 10(11) PLTs). Compared to the
      Spectra machine, the Trima v4 machine showed higher collection efficiencies (CEs)
      and shorter processing time and complied better with the programmed target (SU
      PCs, 3.24 x 10(11) PLTs vs. 3.70 x 10(11) PLTs; DU-PCs, 6.87 x 10(11) PLTs vs.
      7.56 x 10(11) PLTs). Harvests of the Spectra machine (DU-PCs) exceeded the target
      by 40 percent, which resulted in high PLT loss for donors. A longer processing
      time resulted in some higher CEs (SU-PCs, 53%; DU-PCs, 58%), which could
      contribute to this result. PLT recruitment compensated PLT loss to some extent.
      CONCLUSION: The major finding was that the newer devices (COM.TEC and Trima) gave
      more predictable yields than the older devices (AS.TEC204 and Spectra) and
      resulted in lower PLT deficit. PLT software should be improved to minimize
      relevant variations of collected yields regarding the programmed target.

PMID- 15847671
TI  - Transfusion-related exposure to the plasticizer di(2-ethylhexyl)phthalate in
      patients receiving plateletpheresis concentrates.
AB  - BACKGROUND: Di(2-ethylhexyl)phthalate (DEHP) is a plasticizer that can leach from
      medical devices including storage bags for plateletpheresis concentrates (PCs).
      In this study, the DEHP exposure to patients receiving PCs was determined and
      several variables were evaluated to reduce DEHP load to PC recipients. STUDY
      DESIGN AND METHODS: In 12 patients, serum DEHP was assessed before and after PC
      transfusion. For in vitro investigations, PCs were produced either with donor
      plasma or with 65 percent additive solution (AS; T-Sol) and stored for 5 days.
      Washing of PCs was performed according to AABB standards. DEHP levels were
      determined by gas chromatography-mass spectrometry. RESULTS: Transfusion of PCs
      led to a significant increase in serum DEHP. DEHP levels in the PCs continuously
      increased during storage, although the accumulation of DEHP was less in PCs
      stored in the AS, T-Sol, than when stored in plasma. Storage-related accumulation
      of DEHP contributed to a major part of the total DEHP load in PCs stored for 5
      days. Washing of PCs led to a reduction of DEHP load. CONCLUSION: Recipients of
      PCs are exposed to DEHP, although the total amount represents only a small
      percentage of the defined tolerable intake. Reduction of storage time, the
      storage of PC in T-Sol, or the exchange of the storage medium before transfusion
      are practicable means to reduce the DEHP load in PC.

PMID- 15847672
TI  - Life-threatening adverse reaction followed by thrombocytopenia after passive
      transfusion of fresh frozen plasma containing anti-CD36 (Nak) isoantibody.
AB  - BACKGROUND: Anti-CD36 isoantibody in blood recipients is reported to cause
      refractoriness to platelet (PLT) transfusions and posttransfusion purpura-like
      syndrome. There are few reports, however, about the effects of passively
      transfused blood products containing this isoantibody on recipients. CASE REPORT:
      A 67-year-old Japanese woman underwent brain surgery. On the 6th postoperative
      day, the patient experienced tightness of the chest and nausea after receiving a
      transfusion of fresh frozen plasma (FFP). When she manifested hypotension, the
      transfusion was discontinued. No cutaneous manifestation was observed. The
      patient's condition gradually improved soon after the administration of steroids.
      RESULTS: Her pretransfusion PLT count was 17.1 x 10(4) per microL. It decreased
      to 1.9 x 10(4) per microL 12 hours after transfusion and recovered to 15.4 x
      10(4) per microL 8 days after transfusion. The donor of the FFP had a Type I CD36
      deficiency. Flow cytometric analysis identified anti-CD36 isoantibody in the FFP.
      The cross-match between the patient's PLTs and the FFP was positive. The FFP
      induced the aggregation of PLTs derived from healthy adults. CONCLUSION: This is
      the first reported case of life-threatening adverse effects and thrombocytopenia
      caused by passively transfused anti-CD36 isoantibody. The possibility of passive
      infusion of this antibody should be considered in the evaluation of life
      threatening transfusion reactions followed by thrombocytopenia.

PMID- 15847673
TI  - The significance of transfusion in the past as a risk for current hepatitis B and
      hepatitis C infection: a study in endoscopy patients.
AB  - BACKGROUND: The objective was to determine the contribution of transfusion in the
      past to the risk of current infection with hepatitis B or C among patients
      attending a large hospital for endoscopic procedures. STUDY DESIGN AND METHODS:
      Blood samples had been tested for hepatitis markers by routine methods. Patients
      completed a comprehensive risk factor questionnaire and results were analyzed
      using computer software. RESULTS: Twenty-seven percent of the 2120 participants
      in the study received transfusions in the past. There was no increase in
      prevalence of hepatitis B among those transfused. Compared with nontransfused
      participants, recipients of blood before the implementation of hepatitis C virus
      (HCV) screening in 1990 had a 4.6-fold increased risk of HCV infection, whereas
      those transfused with screened blood had a 3-fold increased risk. The difference
      between the odds ratios for patients before and after screening was not
      significant. CONCLUSIONS: Because screening has almost completely eliminated HCV
      from the blood supply, our finding of a continuing association of HCV infection
      with transfusion was unexpected. It implies that there are significant other
      nosocomial risks for hepatitis C transmission associated with the clinical
      situations where patients received blood. These should be actively investigated.

PMID- 15847674
TI  - Fatal Yersinia enterocolitica biotype 4 serovar O:3 sepsis after red blood cell
      transfusion.
AB  - BACKGROUND: Although posttransfusion bacterial sepsis is rare, this complication
      is associated with a high mortality rate. CASE REPORT: A fatal case of septic
      shock was observed in a 71-year-old patient following transfusion of contaminated
      red blood cells (RBCs) for refractory anemia. Yersinia enterocolitica was
      isolated from the patient's blood sample and the transfused RBCs. Both strains
      were of bioserotype 4/O:3 and had the same NotI pulsotype. High titers of
      antibodies against Y. enterocolitica were detected in the donor's plasma sample 1
      month after blood donation. The donor reported abdominal discomfort 3.5 months
      before blood collection but had no clinical signs of intestinal infection at the
      time of donation. CONCLUSION: Y. enterocolitica has been identified with
      increased frequency as a causative agent of posttransfusion septic shock. This
      nationwide investigation of these cases led to an estimated incidence of one case
      per 6.5 million RBC units distributed in France. Although rare, this often fatal
      complication remains nonpreventable worldwide owing to the lack of practical
      means for screening RBCs before transfusion.

PMID- 15847675
TI  - Hematopoietic progenitor cell transplantation from a donor with indeterminate
      human immunodeficiency virus antibody status.

PMID- 15847676
TI  - Recombinant human erythropoietin facilitates autologous blood donation in
      children undergoing corrective spinal surgery.

PMID- 15847678
TI  - Breakage rate for red blood cells frozen with 40 percent (wt/vol) glycerol in 800
      mL polyvinylchloride plastic bags stored in rigid cardboard boxes at -80 degrees
      C.

PMID- 15847680
TI  - Human physiologically based pharmacokinetic model for propofol.
AB  - BACKGROUND: Propofol is widely used for both short-term anesthesia and long-term
      sedation. It has unusual pharmacokinetics because of its high lipid solubility.
      The standard approach to describing the pharmacokinetics is by a multi
      compartmental model. This paper presents the first detailed human physiologically
      based pharmacokinetic (PBPK) model for propofol. METHODS: PKQuest, a freely
      distributed software routine http://www.pkquest.com, was used for all the
      calculations. The "standard human" PBPK parameters developed in previous
      applications is used. It is assumed that the blood and tissue binding is
      determined by simple partition into the tissue lipid, which is characterized by
      two previously determined set of parameters: 1) the value of the propofol
      oil/water partition coefficient; 2) the lipid fraction in the blood and tissues.
      The model was fit to the individual experimental data of Schnider et. al.,
      Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60
      minutes later by a one hour constant infusion. RESULTS: The PBPK model provides a
      good description of the experimental data over a large range of input dosage,
      subject age and fat fraction. Only one adjustable parameter (the liver clearance)
      is required to describe the constant infusion phase for each individual subject.
      In order to fit the bolus injection phase, for 10 or the 24 subjects it was
      necessary to assume that a fraction of the bolus dose was sequestered and then
      slowly released from the lungs (characterized by two additional parameters). The
      average weighted residual error (WRE) of the PBPK model fit to the both the bolus
      and infusion phases was 15%; similar to the WRE for just the constant infusion
      phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental
      model. CONCLUSION: A PBPK model using standard human parameters and a simple
      description of tissue binding provides a good description of human propofol
      kinetics. The major advantage of a PBPK model is that it can be used to predict
      the changes in kinetics produced by variations in physiological parameters. As
      one example, the model simulation of the changes in pharmacokinetics for morbidly
      obese subjects is discussed.

PMID- 15847682
TI  - Using co-occurrence network structure to extract synonymous gene and protein
      names from MEDLINE abstracts.
AB  - BACKGROUND: Text-mining can assist biomedical researchers in reducing information
      overload by extracting useful knowledge from large collections of text. We
      developed a novel text-mining method based on analyzing the network structure
      created by symbol co-occurrences as a way to extend the capabilities of knowledge
      extraction. The method was applied to the task of automatic gene and protein name
      synonym extraction. RESULTS: Performance was measured on a test set consisting of
      about 50,000 abstracts from one year of MEDLINE. Synonyms retrieved from curated
      genomics databases were used as a gold standard. The system obtained a maximum F
      score of 22.21% (23.18% precision and 21.36% recall), with high efficiency in the
      use of seed pairs. CONCLUSION: The method performs comparably with other studied
      methods, does not rely on sophisticated named-entity recognition, and requires
      little initial seed knowledge.

PMID- 15847681
TI  - A method for the prediction of GPCRs coupling specificity to G-proteins using
      refined profile Hidden Markov Models.
AB  - BACKGROUND: G- Protein coupled receptors (GPCRs) comprise the largest group of
      eukaryotic cell surface receptors with great pharmacological interest. A broad
      range of native ligands interact and activate GPCRs, leading to signal
      transduction within cells. Most of these responses are mediated through the
      interaction of GPCRs with heterotrimeric GTP-binding proteins (G-proteins). Due
      to the information explosion in biological sequence databases, the development of
      software algorithms that could predict properties of GPCRs is important.
      Experimental data reported in the literature suggest that heterotrimeric G
      proteins interact with parts of the activated receptor at the transmembrane helix
      intracellular loop interface. Utilizing this information and membrane topology
      information, we have developed an intensive exploratory approach to generate a
      refined library of statistical models (Hidden Markov Models) that predict the
      coupling preference of GPCRs to heterotrimeric G-proteins. The method predicts
      the coupling preferences of GPCRs to Gs, Gi/o and Gq/11, but not G12/13
      subfamilies. RESULTS: Using a dataset of 282 GPCR sequences of known coupling
      preference to G-proteins and adopting a five-fold cross-validation procedure, the
      method yielded an 89.7% correct classification rate. In a validation set
      comprised of all receptor sequences that are species homologues to GPCRs with
      known coupling preferences, excluding the sequences used to train the models, our
      method yields a correct classification rate of 91.0%. Furthermore, promiscuous
      coupling properties were correctly predicted for 6 of the 24 GPCRs that are known
      to interact with more than one subfamily of G-proteins. CONCLUSION: Our method
      demonstrates high correct classification rate. Unlike previously published
      methods performing the same task, it does not require any transmembrane topology
      prediction in a preceding step. A web-server for the prediction of GPCRs coupling
      specificity to G-proteins available for non-commercial users is located at
      http://bioinformatics.biol.uoa.gr/PRED-COUPLE.

PMID- 15847684
TI  - Trade related infections: farther, faster, quieter.
AB  - Modern global trading traffics large volumes of diverse products rapidly to a
      broad geographic area of the world. When emergent infections enter this system in
      traded products their transmission is amplified. With truly novel emergent
      infections with long incubation periods, such as Human Immunodeficiency Virus
      (HIV) or variant Creutzfeld Jacob Disease (vCJD), this transmission may silently
      disseminate infection to far distant populations prior to detection. We describe
      the chronology of two such "stealth infections," vCJD and HIV, and the
      production, processing, and distribution changes that coincided with their
      emergence. The concept of "vector products" is introduced. A brief case study of
      HIV incursion in Japan is presented in illustration. Careful "multisectoral"
      analysis of such events can suggest ecologically critical pathways of emergence
      for further research. Such analyses emphasize the urgency of implementing safety
      measures when pathogens enter globally traded products.

PMID- 15847683
TI  - Reactions to treatment debriefing among the participants of a placebo controlled
      trial.
AB  - BACKGROUND: A significant proportion of trial participants respond to placebos
      for a variety of conditions. Despite the common conduct of these trials and the
      strong emphasis placed on informed consent, very little is known about informing
      participants about their individual treatment allocation at trial closure. This
      study aims to address this gap in the literature by exploring treatment beliefs
      and reactions to feedback about treatment allocation in the participants of a
      placebo-controlled randomized clinical trial (RCT). METHODS: Survey of trial
      participants using a semi-structured questionnaire including close and open-ended
      questions administered as telephone interviews and postal questionnaires. Trial
      participants were enrolled in a double-blind placebo-controlled RCT evaluating
      the effectiveness of corticosteroid for heel pain (ISRCTN36539116). The trial had
      closed and participants remained blind to treatment allocation. We assessed
      treatment expectations, the percentage of participants who wanted to be informed
      about their treatment allocation, their ability to guess and reactions to
      debriefing. RESULTS: Forty-six (73%) contactable participants responded to our
      survey. Forty-two were eligible (four participants with bilateral disease were
      excluded as they had received both treatments). Most (79%) participants did not
      have any expectations prior to receiving treatment, but many 'hoped' that
      something would help. Reasons for not having high expectations included the
      experimental nature of their care and possibility that they may get a placebo.
      Participants were hopeful because their pain was so severe and because they
      trusted the staff and services. Most (83%) wanted to be informed about their
      treatment allocation and study results. Over half (55%) said they could not guess
      which treatment they had been randomized to, and many of those who attempted a
      guess were incorrect. Reactions to treatment debriefing were generally positive,
      including in placebo responders. CONCLUSION: Our study suggests that most trial
      participants want to be informed about their treatment allocation and trial
      results. Further research is required to develop measure of hope and expectancy
      and to rigorously evaluate the effects of debriefing prospectively.

PMID- 15847685
TI  - Global health priorities - priorities of the wealthy?
AB  - Health has gained importance on the global agenda. It has become recognized in
      forums where it was once not addressed. In this article three issues are
      considered: global health policy actors, global health priorities and the means
      of addressing the identified health priorities. I argue that the arenas for
      global health policy-making have shifted from the public spheres towards arenas
      that include the transnational for-profit sector. Global health policy has become
      increasingly fragmented and verticalized. Infectious diseases have gained ground
      as global health priorities, while non-communicable diseases and the broader
      issues of health systems development have been neglected. Approaches to tackling
      the health problems are increasingly influenced by trade and industrial interests
      with the emphasis on technological solutions.

PMID- 15847686
TI  - Behavioral and neuroendocrine consequences of social subjugation across
      adolescence and adulthood.
AB  - BACKGROUND: Social subjugation is a very significant and natural stressor in the
      animal kingdom. Adult animals defeated and subjugated during establishment of
      dominance hierarchies or territorial encounters can be highly submissive in
      future agonistic interactions. While much is know about the biological and
      behavioral consequences of winning and losing fights in adulthood, little is
      known about adolescence; a developmental period noted for impulsivity and
      heightened agonistic behavior. The present studies were undertaken to determine
      if the behavioral and neuroendocrine consequences of social subjugation are
      comparable in adolescent versus adult Syrian golden hamsters (Mesocricetus
      auratus). Male siblings were studied from adolescence into adulthood following
      exposure to counterbalanced episodes of either a benign stressor, i.e., isolation
      in a novel cage, or the more severe stressor of social subjugation. RESULTS: As
      adults, hamsters with a history of social subjugation in adolescence show high
      levels of aggression toward intruders as compared to siblings subjugated in
      adulthood. Sibling controls subjugated in adulthood are highly submissive with
      little or no aggressive behavior. However, when subjugated in adulthood, hamsters
      with the earlier history of subjugation are no different than their sibling
      controls, i.e., adult subjugation promotes submissive behavior. Sexual motivation
      is high in adult hamsters with adolescent subjugation and testosterone levels
      remained stable over adulthood. In contrast, sibling controls subjugated in
      adulthood show lower levels of sexual motivation and reduced levels of
      testosterone. Release of cortisol during agonistic encounters is blunted in
      animals subjugated in adolescence but not adulthood. Measures of anxiety are
      reduced in hamsters with adolescent subjugation as compared to their sibling
      controls. CONCLUSION: These data demonstrate a pronounced difference in behavior
      and neuroendocrinology between adolescent and adult hamsters in their response to
      social subjugation and suggest adolescence is a resilient period in development.

PMID- 15847687
TI  - International nurse recruitment and NHS vacancies: a cross-sectional analysis.
AB  - BACKGROUND: Foreign-trained nurse recruits exceeded the number of new British
      trained recruits on the UK nurse register for the first time in 2001. As the
      nursing shortage continues, health care service providers rely increasingly on
      overseas nurses to fill the void. Which areas benefit the most? And where would
      the NHS be without them? METHODS: Using cross-sectional data from the 2004
      Nursing and Midwifery Council register, nurse resident postcodes are mapped to
      Strategic Health Authorities to see where foreign recruits locate and how they
      affect nurse shortages throughout the UK. RESULTS: Areas with the highest vacancy
      rates also have the highest representation of foreign recruits, with 24% of
      foreign-trained nurses in the UK residing in the London area and another 16% in
      the SouthEast (comparable numbers for British-trained nurses are 11% and 13%,
      respectively). Without foreign recruitment, vacancy rates could be up to five
      times higher (three times higher if only Filipino recruits remained). CONCLUSION:
      The UK heavily relies on foreign recruitment to fill vacancies, without which the
      staffing crisis would be far worse, particularly in high vacancy areas.

PMID- 15847688
TI  - Crosstalk regulation among group 2-sigma factors in Synechocystis PCC6803.
AB  - BACKGROUND: The cyanobacterium Synechocystis PCC6803 contains one group 1 (sigA)
      and four group 2 (sigB, sigC, sigD and sigE) sigma factors. The activity of these
      multiple sigma factors determines the transcriptional program of this bacterium.
      We wanted to study the role of the group 2 sigma factors in Synechocystis. We
      have therefore constructed mutants of each of the group 2 sigma factors and
      investigated their crosstalk. RESULTS: We used quantitative RT-PCR analysis to
      measure the relative abundance of the sig mRNAs in the four sigma mutants. Our
      data indicate that a network of mutual transcriptional regulation links the
      expression of the sigma genes. Accordingly, an environmental stress acting on
      only one of the sigma factors will indirectly modify the expression of most of
      the other sigma factors. This was confirmed by the transcriptional analysis of
      the sig mRNAs as a function of nitrogen starvation. CONCLUSION: Taken together,
      our observations suggest that the crosstalk regulation between all group 1 and
      group 2 genes could be important for the adaptation of the bacterium to different
      environmental and physiological conditions.

PMID- 15847689
TI  - The effectiveness of extra corporeal shock wave therapy for plantar heel pain: a
      systematic review and meta-analysis.
AB  - BACKGROUND: There is considerable controversy regarding the effectiveness of
      extracorporeal shock wave therapy in the management of plantar heel pain. Our aim
      was to conduct a systematic review of randomised controlled trials to investigate
      the effectiveness of extracorporeal shock wave therapy and to produce a precise
      estimate of the likely benefits of this therapy. METHODS: We conducted a
      systematic review of all randomised controlled trials (RCTs) identified from the
      Cochrane Controlled trials register, MEDLINE, EMBASE and CINAHL from 1966 until
      September 2004. We included randomised trials which evaluated extracorporeal
      shock wave therapy used to treat plantar heel pain. Trials comparing extra
      corporeal shock wave therapy with placebo or different doses of extra corporeal
      shock wave therapy were considered for inclusion in the review. We independently
      applied the inclusion and exclusion criteria to each identified randomised
      controlled trial, extracted data and assessed the methodological quality of each
      trial. RESULTS: Six RCTs (n = 897) permitted a pooled estimate of effectiveness
      based on pain scores collected using 10 cm visual analogue scales for morning
      pain. The estimated weighted mean difference was 0.42 (95% confidence interval
      0.02 to 0.83) representing less than 0.5 cm on a visual analogue scale. There was
      no evidence of heterogeneity and a fixed effects model was used. CONCLUSION: A
      meta-analysis of data from six randomised-controlled trials that included a total
      of 897 patients was statistically significant in favour of extracorporeal shock
      wave therapy for the treatment of plantar heel pain but the effect size was very
      small. A sensitivity analysis including only high quality trials did not detect a
      statistically significant effect.

PMID- 15847690
TI  - The evolution of the Global Burden of Disease framework for disease, injury and
      risk factor quantification: developing the evidence base for national, regional
      and global public health action.
AB  - Reliable, comparable information about the main causes of disease and injury in
      populations, and how these are changing, is a critical input for debates about
      priorities in the health sector. Traditional sources of information about the
      descriptive epidemiology of diseases, injuries and risk factors are generally
      incomplete, fragmented and of uncertain reliability and comparability. Lack of a
      standardized measurement framework to permit comparisons across diseases and
      injuries, as well as risk factors, and failure to systematically evaluate data
      quality have impeded comparative analyses of the true public health importance of
      various conditions and risk factors. As a consequence the impact of major
      conditions and hazards on population health has been poorly appreciated, often
      leading to a lack of public health investment. Global disease and risk factor
      quantification improved dramatically in the early 1990s with the completion of
      the first Global Burden of Disease Study. For the first time, the comparative
      importance of over 100 diseases and injuries, and ten major risk factors, for
      global and regional health status could be assessed using a common metric
      (Disability-Adjusted Life Years) which simultaneously accounted for both
      premature mortality and the prevalence, duration and severity of the non-fatal
      consequences of disease and injury. As a consequence, mental health conditions
      and injuries, for which non-fatal outcomes are of particular significance, were
      identified as being among the leading causes of disease/injury burden worldwide,
      with clear implications for policy, particularly prevention. A major achievement
      of the Study was the complete global descriptive epidemiology, including
      incidence, prevalence and mortality, by age, sex and Region, of over 100 diseases
      and injuries. National applications, further methodological research and an
      increase in data availability have led to improved national, regional and global
      estimates for 2000, but substantial uncertainty around the disease burden caused
      by major conditions, including, HIV, remains. The rapid implementation of cost
      effective data collection systems in developing countries is a key priority if
      global public policy to promote health is to be more effectively informed.

PMID- 15847691
TI  - The global diet: trade and novel infections.
AB  - Practices designed to meet the demands of global trade can amplify food safety
      problems. Ever-increasing pressure to churn out more product and better sides of
      beef has generated processes that compromise existing safety measures. Among the
      concerns are intensified food production, use of antimicrobials and hormones as
      growth promoters, and poor sanitary infrastructure in some food producing
      countries. Accompanying the innovations designed to serve the diversifying global
      palate are emerging and re-emerging infectious diseases, or "trade-related
      infections." The joint efforts of international public health and industry are
      required to effectively address these growing health challenges.

PMID- 15847692
TI  - Increased DNA microarray hybridization specificity using sscDNA targets.
AB  - BACKGROUND: The most widely used amplification method for microarray analysis of
      gene expression uses T7 RNA polymerase-driven in vitro transcription (IVT) to
      produce complementary RNA (cRNA) that can be hybridized to arrays. However,
      multiple rounds of amplification are required when assaying very small amounts of
      starting RNA. Moreover, certain cRNA-DNA mismatches are more stable than the
      analogous cDNA-DNA mismatches and this might increase non-specific hybridization.
      We sought to determine whether a recently developed linear isothermal
      amplification method (ribo-SPIA) that produces single stranded cDNA would offer
      advantages over traditional IVT-based methods for microarray-based analyses of
      transcript expression. RESULTS: A single round of ribo-SPIA amplification
      produced sufficient sscDNA for hybridizations when as little as 5 ng of starting
      total RNA was used. Comparisons of probe set signal intensities obtained from
      replicate amplifications showed consistently high correlations (r = 0.99). We
      compared gene expression in two different human RNA samples using ribo-SPIA.
      Compared with one round IVT, ribo-SPIA had a larger dynamic range and correlated
      better with quantitative PCR results even though we used 1000-fold less starting
      RNA. The improved dynamic range was associated with decreases in hybridization to
      mismatch control probes. CONCLUSION: The use of amplified sscDNA may offer
      substantial advantages over IVT-based amplification methods, especially when very
      limited amounts of starting RNA are available. The use of sscDNA targets instead
      of cRNA targets appears to improve hybridization specificity.

PMID- 15847693
TI  - Response of SI cortex to ipsilateral, contralateral and bilateral flutter
      stimulation in the cat.
AB  - BACKGROUND: While SII cortex is considered to be the first cortical stage of the
      pathway that integrates tactile information arising from both sides of the body,
      SI cortex is generally not considered as a region in which neuronal response is
      modulated by simultaneous stimulation of bilateral (and mirror-image) skin sites.
      RESULTS: Optical intrinsic signal imaging was used to evaluate the response of SI
      and SII in the same hemisphere to 25 Hz sinusoidal vertical skin displacement
      stimulation ("skin flutter") applied contralaterally, ipsilaterally, and
      bilaterally (simultaneously) to the central pads of the forepaws. A localized
      increase in absorbance in both SI and SII occurred in response to both
      contralateral and bilateral flutter stimulation. Ipsilateral flutter stimulation
      evoked a localized increase in absorbance in SII, but little or no change in SI
      absorbance. In the forepaw representational region of SI, however, bilateral
      stimulation of the central pads evoked a response substantially smaller
      (approximately 30-35% smaller) than the response to flutter stimulation of the
      contralateral central pad. CONCLUSION: The finding that the response of SI cortex
      to bilateral central pad flutter stimulation is substantially smaller than the
      response evoked by a contralateral flutter stimulus, together with the recently
      published observation that a region located posteriorly in SII responds with a
      substantially larger response to a bilateral flutter stimulus than the response
      evoked from the contralateral central pad, lead us to propose that the SI
      activity evoked by contralateral skin stimulation is suppressed/inhibited (via
      corticocortical connections between SII and SI in the same hemisphere) by the
      activity a simultaneous ipsilateral skin stimulus evokes in posterior SII.

PMID- 15847695
TI  - Rationale, design and conduct of a comprehensive evaluation of a school-based
      peer-led anti-smoking intervention in the UK: the ASSIST cluster randomised trial
      [ISRCTN55572965].
AB  - BACKGROUND: To date, no school-based intervention has been proven to be effective
      in preventing adolescent smoking, despite continuing concern about smoking levels
      amongst young people in the United Kingdom. Although formal teacher-led smoking
      prevention interventions are considered unlikely to be effective, peer-led
      approaches to reducing smoking have been proposed as potentially valuable.
      METHODS/DESIGN: ASSIST (A Stop Smoking in Schools Trial) is a comprehensive,
      large-scale evaluation to rigorously test whether peer supporters in Year 8 (age
      11-12) can be recruited and trained to effect a reduction in smoking uptake among
      their fellow students. The evaluation is employing a cluster randomised
      controlled trial (RCT) design with secondary school as the unit of randomisation,
      and is being undertaken in 59 schools in South East Wales and the West of
      England. Embedded within the trial are an economic evaluation of the intervention
      costs, a process evaluation to provide detailed information on how the
      intervention was delivered and received, and an analysis of social networks to
      consider whether such a peer group intervention could work amongst schoolchildren
      in this age group. Schools were randomised to either continue with normal smoking
      education (n = 29 schools, 5562 students), or to do so and additionally receive
      the ASSIST intervention (n = 30 schools, 5481 students). No schools withdrew once
      the trial had started, and the intervention was successfully implemented in all
      30 schools, with excellent participation rates from the peer supporters. The
      primary outcome is regular (weekly) smoking, validated by salivary cotinine, and
      this outcome has been obtained for 94.4%, 91.0% and 95.6% of eligible students at
      baseline, immediate post-intervention, and one-year follow-up respectively.
      DISCUSSION: Comprehensive evaluations of complex public health interventions of
      this scale and nature are rare in the United Kingdom. This paper demonstrates the
      feasibility of conducting cluster RCTs of complex public health interventions in
      schools, and how the rigour of such designs can be maximised both by thorough
      implementation of the protocol and by broadening the scope of questions addressed
      in the trial by including additional evaluative components.

PMID- 15847694
TI  - Sequence determinants of protein aggregation: tools to increase protein
      solubility.
AB  - Escherichia coli is one of the most widely used hosts for the production of
      recombinant proteins. However, very often the target protein accumulates into
      insoluble aggregates in a misfolded and biologically inactive form. Bacterial
      inclusion bodies are major bottlenecks in protein production and are hampering
      the development of top priority research areas such structural genomics.
      Inclusion body formation was formerly considered to occur via non-specific
      association of hydrophobic surfaces in folding intermediates. Increasing
      evidence, however, indicates that protein aggregation in bacteria resembles to
      the well-studied process of amyloid fibril formation. Both processes appear to
      rely on the formation of specific, sequence-dependent, intermolecular
      interactions driving the formation of structured protein aggregates. This
      similarity in the mechanisms of aggregation will probably allow applying anti
      aggregational strategies already tested in the amyloid context to the less
      explored area of protein aggregation inside bacteria. Specifically, new sequence
      based approaches appear as promising tools to tune protein aggregation in
      biotechnological processes.

PMID- 15847696
TI  - How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation.
AB  - Recognition of temperature is a critical element of sensory perception and allows
      us to evaluate both our external and internal environments. In vertebrates, the
      somatosensory system can discriminate discrete changes in ambient temperature,
      which activate nerve endings of primary afferent fibers. These thermosensitive
      nerves can be further segregated into those that detect either innocuous or
      noxious (painful) temperatures; the latter neurons being nociceptors. We now know
      that thermosensitive afferents express ion channels of the transient receptor
      potential (TRP) family that respond at distinct temperature thresholds, thus
      establishing the molecular basis for thermosensation. Much is known of those
      channels mediating the perception of noxious heat; however, those proposed to be
      involved in cool to noxious cold sensation, TRPM8 and TRPA1, have only recently
      been described. The former channel is a receptor for menthol, and links the
      sensations provided by this and other cooling compounds to temperature
      perception. While TRPM8 almost certainly performs a critical role in cold
      signaling, its part in nociception is still at issue. The latter channel, TRPA1,
      is activated by the pungent ingredients in mustard and cinnamon, but has also
      been postulated to mediate our perception of noxious cold temperatures. However,
      a number of conflicting reports have suggested that the role of this channel in
      cold sensation needs to be confirmed. Thus, the molecular logic for the
      perception of cold-evoked pain remains enigmatic. This review is intended to
      summarize our current understanding of these cold thermoreceptors, as well as
      address the current controversy regarding TRPA1 and cold signaling.

PMID- 15847698
TI  - GIDEON: a comprehensive Web-based resource for geographic medicine.
AB  - GIDEON (Global Infectious Diseases and Epidemiology Network) is a web-based
      computer program designed for decision support and informatics in the field of
      Geographic Medicine. The first of four interactive modules generates a ranked
      differential diagnosis based on patient signs, symptoms, exposure history and
      country of disease acquisition. Additional options include syndromic disease
      surveillance capability and simulation of bioterrorism scenarios. The second
      module accesses detailed and current information regarding the status of 338
      individual diseases in each of 220 countries. Over 50,000 disease images, maps
      and user-designed graphs may be downloaded for use in teaching and preparation of
      written materials. The third module is a comprehensive source on the use of 328
      anti-infective drugs and vaccines, including a listing of over 9,500
      international trade names. The fourth module can be used to characterize or
      identify any bacterium or yeast, based on laboratory phenotype. GIDEON is an up
      to-date and comprehensive resource for Geographic Medicine.

PMID- 15847697
TI  - Comparison of amplification enzymes for Hepatitis C Virus quasispecies analysis.
AB  - BACKGROUND: Hepatitis C virus (HCV) circulates as quasispecies (QS), whose
      evolution is associated with pathogenesis. Previous studies have suggested that
      the use of thermostable polymerases without proofreading function may contribute
      to inaccurate assessment of HCV QS. In this report, we compared non-proofreading
      (Taq) with proofreading (Advantage High Fidelity-2; HF-2) polymerases in the
      sensitivity, robustness, and HCV QS diversity and complexity in the second
      envelope glycoprotein gene hypervariable region 1 (E2-HVR1) on baseline specimens
      from 20 patients in the HALT-C trial and in a small cohort of 12 HCV/HIV co
      infected patients. QS diversity and complexity were quantified using heteroduplex
      mobility assays (HMA). RESULTS: The sensitivities of both enzymes were comparable
      at 50 IU/ml, although HF-2 was more robust and slightly more sensitive than Taq.
      Both enzymes generated QS diversity and complexity scores that were correlated (r
      = 0.68; p < 0.0001, and r = 0.47; p < 0.01; Spearman's rank correlation). QS
      diversity was similar for both Taq and HF-2 enzymes, although there was a trend
      for higher diversity in samples amplified by Taq (p = 0.126). Taq amplified
      samples yielded complexity scores that were significantly higher than HF-2
      samples (p = 0.033). HALT-C patients who were HCV positive or negative following
      20 weeks of pegylated IFN plus ribavirin therapy had similar QS diversity scores
      for Taq and HF-2 samples, and there was a trend for higher complexity scores from
      Taq as compared with HF-2 samples. Among patients with HCV and HIV co-infection,
      HAART increased HCV QS diversity and complexity as compared with patients not
      receiving therapy, suggesting that immune reconstitution drives HCV QS evolution.
      However, diversity and complexity scores were similar for both HF-2 and Taq
      amplified specimens. CONCLUSION: The data suggest that while Taq may overestimate
      HCV QS complexity, its use does not significantly affect results in cohort-based
      studies of HCV QS analyzed by HMA. However, the use of proofreading enzymes such
      as HF-2 is recommended for more accurate characterization of HCV QS in vivo.

PMID- 15847699
TI  - Globalization and Health.
AB  - This debut editorial of Globalization and Health introduces the journal, briefly
      delineating its goals and objectives and outlines its scope of subject matter.
      'Open Access' publishing is expected to become an increasingly important format
      for peer reviewed academic journals and that Globalization and Health is 'Open
      Access' is appropriate. The rationale behind starting a journal dedicated to
      globalization and health is three fold:Firstly: Globalization is reshaping the
      social geography within which we might strive to create health or prevent
      disease. The determinants of health - be they a SARS virus or a predilection for
      fatty foods - have joined us in our global mobility. Driven by economic
      liberalization and changing technologies, the phenomenon of 'access' is likely to
      dominate to an increasing extent the unfolding experience of human disease and
      wellbeing.Secondly: Understanding globalization as a subject matter itself needs
      certain benchmarks and barometers of its successes and failings. Health is one
      such barometer. It is a marker of social infrastructure and social welfare and as
      such can be used to either sound an alarm or give a victory cheer as our
      interconnectedness hurts and heals the populations we serve.And lastly: In as
      much as globalization can have an effect on health, it is also true that health
      and disease has an effect on globalization as exemplified by the existence of
      quarantine laws and the devastating economic effects of the AIDS pandemic.A
      balanced view would propose that the effects of globalization on health (and
      health systems) are neither universally good nor bad, but rather context
      specific. If the dialogue pertaining to globalization is to be directed or biased
      in any direction, then it must be this: that we consider the poor first.

PMID- 15847700
TI  - Globalization and Health: Exploring the opportunities and constraints for health
      arising from globalization.
AB  - The tremendous benefits which have been conferred to almost 5 billion people
      through improved technologies and knowledge highlights the concomitant challenge
      of bringing these changes to the 1 billion people living mostly in sub-Saharan
      Africa and South Asia who are yet to benefit. There is a growing awareness of the
      need to reduce human suffering and of the necessary participation of governments,
      non-government organizations and industry within this process. This awareness has
      recently translated into new funding mechanisms to address HIV/Aids and vaccines,
      a global push for debt relief and better trade opportunities for the poorest
      countries, and recognition of how global norms that address food safety,
      infectious diseases and tobacco benefit all. 'Globalization and Health' will
      encourage an exchange of views on how the global architecture for health
      governance needs to changes in the light of global threats and opportunities.

PMID- 15847701
TI  - Identification of a novel Rev-interacting cellular protein.
AB  - BACKGROUND: Human cell types respond differently to infection by human
      immunodeficiency virus (HIV). Defining specific interactions between host cells
      and viral proteins is essential in understanding how viruses exploit cellular
      functions and the innate strategies underlying cellular control of HIV
      replication. The HIV Rev protein is a post-transcriptional inducer of HIV gene
      expression and an important target for interaction with cellular proteins.
      Identification of Rev-modulating cellular factors may eventually contribute to
      the design of novel antiviral therapies. RESULTS: Yeast-two hybrid screening of a
      T-cell cDNA library with Rev as bait led to isolation of a novel human cDNA
      product (16.4.1). 16.4.1-containing fusion proteins showed predominant
      cytoplasmic localization, which was dependent on CRM1-mediated export from the
      nucleus. Nuclear export activity of 16.4.1 was mapped to a 60 amino acid region
      and a novel transport signal identified. Interaction of 16.4.1 with Rev in human
      cells was shown in a mammalian two-hybrid assay and by colocalization of Rev and
      16.4.1 in nucleoli, indicating that Rev can recruit 16.4.1 to the
      nucleus/nucleoli. Rev-dependent reporter expression was inhibited by
      overexpressing 16.4.1 and stimulated by siRNAs targeted to 16.4.1 sequences,
      demonstrating that 16.4.1 expression influences the transactivation function of
      Rev. CONCLUSION: These results suggest that 16.4.1 may act as a modulator of Rev
      activity. The experimental strategies outlined in this study are applicable to
      the identification and biological characterization of further novel Rev
      interacting cellular factors.

PMID- 15847702
TI  - The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines
      VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy +/
      chemotherapy.
AB  - BACKGROUND: Several parameters of the tumor microenvironment, such as hypoxia,
      inflammation and angiogenesis, play a critical role in tumor aggressiveness and
      treatment response. A major question remains if these markers can be used to
      stratify patients to certain treatment protocols. The purpose of this study was
      to investigate the inter-relationship and the prognostic significance of several
      biological and clinicopathological parameters in patients with head and neck
      squamous cell carcinoma (HNSCC) treated by radiotherapy +/- chemotherapy.
      METHODS: We used two subgroups of a retrospective series for which CT-determined
      tumoral perfusion correlated with local control. In the first subgroup (n = 67),
      immunohistochemistry for carbonic anhydrase IX (CA IX) and glucose transporter-1
      (GLUT-1) was performed on the pretreatment tumor biopsy. In the second subgroup
      (n = 34), enzyme linked immunosorbent assay (ELISA) was used to determine
      pretreatment levels of the cytokines vascular endothelial growth factor (VEGF)
      and interleukin-6 (IL-6) in serum. Correlation was investigated between tumoral
      perfusion and each of these biological markers, as well as between the markers
      mutually. The prognostic value of these microenvironmental parameters was also
      evaluated. RESULTS: For CA IX and GLUT-1, the combined assessment of patients
      with both markers expressed above the median showed an independent correlation
      with local control (p = 0.02) and disease-free survival (p = 0.04) with a trend
      for regional control (p = 0.06). In the second subgroup, IL-6 pretreatment serum
      level above the median was the only independent predictor of local control (p =
      0.009), disease-free survival (p = 0.02) and overall survival (p = 0.005).
      CONCLUSION: To our knowledge, we are the first to report a link in HNSCC between
      IL-6 pretreatment serum levels and radioresistance in vivo. This link is
      supported by the strong prognostic association of pretreatment IL-6 with local
      control, known to be the most important parameter to judge radiotherapy
      responses. Furthermore, the combined assessment of CA IX and GLUT-1 correlated
      independently with prognosis. This is a valuable indication that a combined
      approach is important in the investigation of prognostic markers.

PMID- 15847703
TI  - Prevalence and burden of self-reported blindness and low vision for individuals
      living in institutions: a nationwide survey.
AB  - BACKGROUND: The prevalence of self-reported low vision (LV) and blindness, and
      their associated disabilities, handicaps and socio-economic consequences for
      individuals living in institutions are poorly documented. METHODS: 2,075
      institutions were selected at random and eight individuals were picked at random
      from the list of residents. Three groups of individuals were defined: blind, LV,
      and a control group (CG). These were compared after adjustment for age and co
      morbidities. Of the 15,403 individuals, 14,603 interviews (94.9%) were completed.
      RESULTS: The prevalence of blindness was 1.6% and the LV 13.4%. Blind individuals
      needed assistance more often (OR: 2.65 to 11.35) than CG members while the
      assistance required by LV individuals was similar to that for the CG. Blind
      individuals required institution adaptation (building and furniture changes) more
      often than the CG. Blind (57.9%) and LV individuals (35.4%) were more often
      registered for social allowances. Monthly social allowances were EUR 86 higher
      for blind than LV individuals. Monthly family incomes were found to be similar
      between the three groups (from EUR 782 to 797). Social and demographic data,
      institution description, income, handicaps, disabilities, social allowances and
      details of daily activities were collected interviews. CONCLUSION: The results
      demonstrate the impact of self-reported blindness and LV on daily life for
      patients living in institutions.

PMID- 15847704
TI  - Endemic malaria: an 'indoor' disease in northern Europe. Historical data
      analysed.
AB  - BACKGROUND: Endemic northern malaria reached 68 degrees N latitude in Europe
      during the 19th century, where the summer mean temperature only irregularly
      exceeded 16 degrees C, the lower limit needed for sporogony of Plasmodium vivax.
      Because of the available historical material and little use of quinine, Finland
      was suitable for an analysis of endemic malaria and temperature. METHODS: Annual
      malaria death frequencies during 1800-1870 extracted from parish records were
      analysed against long-term temperature records in Finland, Russia and Sweden.
      Supporting data from 1750-1799 were used in the interpretation of the results.
      The life cycle and behaviour of the anopheline mosquitoes were interpreted
      according to the literature. RESULTS: Malaria frequencies correlated strongly
      with the mean temperature of June and July of the preceding summer, corresponding
      to larval development of the vector. Hatching of imagoes peaks in the middle of
      August, when the temperature most years is too low for the sporogony of
      Plasmodium. After mating some of the females hibernate in human dwellings. If the
      female gets gametocytes from infective humans, the development of Plasmodium can
      only continue indoors, in heated buildings. CONCLUSION: Northern malaria existed
      in a cold climate by means of summer dormancy of hypnozoites in humans and indoor
      transmission of sporozoites throughout the winter by semiactive hibernating
      mosquitoes. Variable climatic conditions did not affect this relationship. The
      epidemics, however, were regulated by the population size of the mosquitoes
      which, in turn, ultimately was controlled by the temperatures of the preceding
      summer.

PMID- 15847705
TI  - Chemotherapy-induced peripheral neuropathy: an increasing concern for
      oncologists.

PMID- 15847706
TI  - First-line therapy for advanced colorectal cancer.
AB  - First-line therapy for advanced colorectal cancer is rapidly moving from
      modulation and infusional administration of fluoropyrimidines in the past decades
      to more complex and more active regimens, with new chemotherapy drugs,
      oxaliplatin and irinotecan, and modulated targeted drugs inhibiting angiogenesis
      or the epidermal growth factor receptor (EGFR). The choice of first-line therapy
      is becoming more complex and is part of a global strategy also integrating
      individual prognostic factors, salvage surgery, and second-line therapy.
      Furthermore, we fear that limited financial resources will also influence the
      management of this disease.

PMID- 15847707
TI  - Second-line therapy for advanced colorectal carcinoma.
AB  - The past decade has witnessed considerable advances in the treatment of
      colorectal cancer (CRC). The emergence and integration into clinical practice of
      new cytotoxic agents, such as irinotecan and oxaliplatin, has had a significant
      impact on outcomes from advanced CRC with median survivals of 18 to 21 months now
      achievable. Improvements in survival as a consequence of using these drugs as
      salvage therapies ultimately led to demonstration of efficacy for both in the
      first-line treatment of CRC. As the importance of second-line therapy is
      increasingly recognized, key issues, such as optimal schedules, chemotherapy
      combinations, and sequential therapy, need to be addressed. The integration of
      newer biologic agents, such as cetuximab and bevacizumab, for which recent data
      have emerged, has further added to the complexities of delivering therapy to
      patients with advanced CRC, heralding a new treatment era for this disease.

PMID- 15847708
TI  - Adjuvant therapy for colon cancer.
AB  - As there have been advances in the treatment of metastatic colorectal cancer,
      exciting developments have also been achieved in the adjuvant treatment of colon
      cancer. At the same time, more questions have been raised, and some controversies
      remain. The results of the MOSAIC trial demonstrated the benefit of adding
      oxaliplatin to 5-fluorouracil (5-FU) and leucovorin (FOLFOX) in adjuvant therapy
      for stage II and III disease, but the optimal duration of therapy and the
      management of toxicities remain to be resolved. Capecitabine is at least
      equivalent to the Mayo Clinic bolus 5-FU and leucovorin regimen in the adjuvant
      treatment of stage III colon cancer with a lower incidence profile of adverse
      events, allowing additional options for patients and physicians. Routine adjuvant
      systemic therapy in all patients with stage II colon cancer is still debatable.
      Although a statistically significant advantage for adjuvant treatment in stage II
      disease was shown for the first time from a large randomized study (QUASAR), the
      subsets of patients who truly benefit from therapy need to be identified. The
      application of pharmacogenetics and pharmacogenomics in adjuvant therapy for
      colorectal cancer will help to distinguish those patients with risk factors and
      to guide individualized therapy.

PMID- 15847709
TI  - Chemotherapy for advanced pancreatic cancer: past, present, and future.
AB  - Advanced pancreatic cancer is a devastating illness characterized by significant
      morbidity and a brief median survival. Although standard chemotherapy with
      gemcitabine achieves only modest improvements in survival and quality of life,
      classic cytotoxic agents, such as 5-fluorouracil, pemetrexed, irinotecan,
      exatecan, cisplatin, or oxaliplatin, given alone or in combination with
      gemcitabine, have not proved superior. Thus, more recent trials have focused on
      targeting the biologic characteristics of pancreatic cancer. Although phase III
      trials of farnesyl transferase and matrix metalloproteinase inhibitors have not
      improved survival, encouraging preliminary results have been observed in phase II
      studies of inhibitors of the vascular endothelial growth factor and the epidermal
      growth factor receptor.

PMID- 15847710
TI  - Chemoradiotherapy for gastrointestinal cancers.
AB  - New combinations of chemotherapy with radiotherapy for gastrointestinal cancers
      are showing evidence that improved outcomes may result from toxicity profiles
      associated with "targeted" systemic radiosensitizing agents. These new agents are
      also clinically attractive owing to such factors as oral bioavailability and
      patient dosing schedules, making them practical and convenient compared with
      older intravenous administration requirements. Several new classes of
      radiosensitizing agents are discussed here and underscore aspects of molecular
      activation in tumors rather than normal tissues because of differences in
      pathways of metabolism or based on the process of tumor-associated angiogenesis.

PMID- 15847711
TI  - Docetaxel-based chemotherapy trials in androgen-independent prostate cancer:
      first demonstration of a survival benefit.

PMID- 15847712
TI  - Adjuvant chemotherapy for transitional cell carcinoma of the bladder: paradigms
      for the design of clinical trials.
AB  - Optimal treatment of high-risk, muscle-invasive bladder cancer involves local and
      systemic therapy. Published trials of adjuvant chemotherapy in bladder cancer are
      limited, but the evidence suggests that the combination of chemotherapy and
      surgery in high-risk patients improves survival. The identification of biologic
      markers with prognostic significance will allow clinicians to better determine
      which patients are at high risk for relapse. The development of newer, less toxic
      drugs with activity in bladder cancer has set the stage for the next generation
      of trials. Several multicenter randomized controlled trials are evaluating new
      chemotherapy regimens in the adjuvant setting. These new trials represent an
      important step forward in improving the treatment of bladder cancer.

PMID- 15847713
TI  - Angiogenesis and prostate cancer: important laboratory and clinical findings.
AB  - Prostate cancer is the leading cause of cancer diagnosis in men and the second
      leading cause of cancer-related death. Androgen ablation is effective initially,
      and progression of disease often occurs in many patients. Although recent reports
      have noted a survival benefit when patients with androgen-independent prostate
      cancer are treated with docetaxel, patients still have disease progression.
      Angiogenesis plays a pivotal role for the growth, invasion, and metastasis of
      prostate cancer. Therefore, antiangiogenesis is a promising new therapeutic
      modality. More than 20 antiangiogenic agents are now in various stages of
      clinical trials. We discuss current knowledge on controlling tumor angiogenesis
      and advances in the development of antiangiogenic agents with promising antitumor
      activity in prostate cancer.

PMID- 15847714
TI  - Chemotherapy for advanced prostate cancer: results of new clinical trials and
      future studies.
AB  - Our understanding of the role of chemotherapy for advanced prostate cancer has
      improved considerably in 2004 with the publication of two large randomized phase
      III trials and the approval by the US Food and Drug Administration of docetaxel
      and prednisone for metastatic hormone-refractory disease. Although treatment is
      still considered palliative in nature, studies of chemotherapy for metastatic
      hormone-refractory prostate cancer (HRPC) have demonstrated improved overall
      survival compared with older regimens as well as clinically significant
      improvements in important endpoints, such as quality of life and time to
      progression. In particular, docetaxel has emerged as first-line therapy on an
      every-3-week schedule for metastatic HRPC, replacing mitoxantrone, as recently
      reported in the TAX327 trial. Docetaxel and estramustine combinations have the
      disadvantage of significant cardiovascular and gastrointestinal toxicity, and
      further use of estramustine is likely unwarranted as first-line therapy. Future
      trials examining novel biologic agents and combination therapies should use
      single-agent docetaxel as the reference standard. The role of chemotherapy for
      advanced disease in the neoadjuvant or adjuvant setting, in biochemically (PSA)
      relapsed patients, and as second-line therapy for relapsed disease, remains a
      subject of active clinical investigation.

PMID- 15847716
TI  - Gatifloxacin Therapy in Otitis Media in Children.

PMID- 15847715
TI  - Secondary hormonal manipulations in prostate cancer.
AB  - Virtually all patients treated with androgen deprivation eventually develop
      progressive clinical or biochemical disease despite this therapy. Despite low
      levels of androgen, the androgen receptor remains active, making secondary
      hormonal therapies a reasonable clinical approach. Considerations for such
      patients include antiandrogen withdrawal, sequential use of antiandrogens,
      adrenal cortex inhibitors, and estrogenic compounds. Collectively, the modest
      activity of these therapies challenges the notion that advancing prostate cancer
      will uniformly become "hormone refractory."

PMID- 15847717
TI  - Sinusitis in HIV: Microbiology and Therapy.
AB  - Rhinosinusitis in the HIV-infected population is an increasingly common finding
      as HIV infection has transitioned toward becoming a chronic medical condition. In
      this patient population, rhinosinusitis may be challenging to diagnose and
      effectively treat. However, adequate diagnostic tools are available, microbial
      identity can be reasonably anticipated based on the CD4 count, and effective
      management strategies can be implemented. This article discusses the diagnostic
      and therapeutic options for HIV-infected patients with rhinosinusitis.

PMID- 15847718
TI  - Cervicofacial Actinomycosis: Diagnosis and Management.
AB  - Cervicofacial actinomycosis is an uncommon but fascinating infection of the head
      and neck. Most cases are odontogenic in origin and occur predominantly in
      immunocompetent individuals. Causative microorganisms are generally of low
      pathogenicity and cause disease only in the setting of antecedent tissue injury.
      The disease process is characterized by the formation of abscesses, fibrosis and
      woody induration of tissues, and draining sinuses that discharge "sulfur
      granules." Cultural isolation of Actinomyces species from clinical specimens, or
      microscopic visualization of gram-positive, non-acid-fast, thin, branching
      filaments in cytologic aspirates or histopathologic sections are the best methods
      of diagnosis of cervicofacial actinomycosis. Penicillin is the drug of choice and
      is usually administered for 2 to 12 months, although short-course treatment may
      cure uncomplicated infection. Surgical therapy is often indicated for curettage
      of bone, resection of necrotic tissue, excision of sinus tracts, and drainage of
      soft tissue abscesses. The prognosis for treated infection is excellent.

PMID- 15847719
TI  - The Use of Macrolides in Treatment of Upper Respiratory Tract Infections.
AB  - Antimicrobial resistance is a growing problem among upper respiratory tract
      pathogens. Resistance to beta-lactam drugs among Streptococcus pneumoniae,
      Haemophilus influenzae, and Streptococcus pyogenes is increasing. As safe and
      well-tolerated antibiotics, macrolides play a key role in the treatment of
      community-acquired upper respiratory tract infections (RTIs). Their broad
      spectrum of activity against gram-positive cocci, such as S. pneumoniae and S.
      pyogenes, atypical pathogens, H. influenzae (azithromycin and clarithromycin),
      and Moraxella catarrhalis, has led to the widespread use of macrolides for
      empiric treatment of upper RTIs and as alternatives for patients allergic to b
      lactams. Macrolide resistance is increasing among pneumococci and recently among
      S. pyogenes, and is associated with increasing use of the newer macrolides, such
      as azithromycin. Ribosomal target modification mediated by erm(A) and erm(B)
      genes and active efflux due to mef(A) and mef(E) are the principal mechanisms of
      resistance in S. pneumoniae and S. pyogenes. Recently, ribosomal protein and RNA
      mutations have been found responsible for acquired resistance to macrolides in S.
      pneumoniae, S. pyogenes, and H. influenzae. Although macrolides are only weakly
      active against macrolide-resistant streptococci species producing an efflux pump
      (mef) and are inactive against pathogens with ribosomal target modification
      (erm), treatment failures are uncommon. Therefore, macrolide therapy, for now,
      remains a good alternative for treatment of upper RTIs; however, continuous
      monitoring of the local resistance patterns is essential.

PMID- 15847720
TI  - Rapid Tests for Influenza.
AB  - A variety of antigen-capture assays are commercially available for the detection
      of influenza. In addition, real-time multiplex polymerase chain reaction (PCR)
      has been used to detect influenza A and B in clinical specimens. The commercial
      assays can be completed in less than 30 minutes and have a sensitivity of at
      least 70% and a specificity of 90%, compared with viral isolation. They are
      useful not only in the diagnosis and treatment of individual patients with
      influenza-like illness but also in surveillance for influenza, decreasing the
      time of nosocomial outbreaks, decreasing the use of laboratory tests, and
      decreasing antibiotic use in patients with influenza. Some of the rapid antigen
      assays, and PCR, can detect the H5N1 and H9N1 viruses. Real-time multiplex PCR
      also detects a variety of respiratory viruses within 6 hours, with only 1 hour of
      hands-on technician time. The widespread use of the rapid tests for influenza is
      changing the practice pattern of physicians who care for patients with influenza.

PMID- 15847721
TI  - Avian Influenza.
AB  - The current epidemic of H5N1 highly pathogenic avian influenza in Southeast Asia
      raises serious concerns that genetic reassortment will result in the next
      influenza pandemic. There have been 164 confirmed cases of human infection with
      avian influenza since 1996. In 2004, there were 45 cases of human H5N1 in Vietnam
      and Thailand, with a mortality rate more than 70%. In addition to the potential
      public health hazard, the current zoonotic epidemic has caused severe economic
      losses. Efforts must be concentrated on early detection of bird outbreaks with
      aggressive culling, quarantining, and disinfection. To prepare for and prevent an
      increase in human cases, it is essential to improve detection methods and
      stockpile effective antivirals. Novel therapeutic modalities, including short
      interfering RNAs and new vaccine strategies that use plasmid-based genetic
      systems, offer promise should a pandemic occur.

PMID- 15847722
TI  - Influenza Vaccine in the Elderly and Chronic Obstructive Pulmonary Disease.
AB  - Influenza viruses are RNA viruses that are a major determinant of morbidity and
      mortality caused by respiratory disease. Influenza is highly contagious and has
      caused epidemics and pandemics for centuries. Most influenza infections are self-
      limited, but lower respiratory tract and cardiac complications can result in
      increases in hospitalizations and deaths. The recommended composition of
      influenza vaccine is updated annually in order to provide a vaccine that is
      antigenically well matched with the new influenza virus strains that are expected
      to cause epidemics. Influenza vaccination significantly reduces mortality;
      however, approximately one third of elderly Americans are not immunized annually.
      The nation's goal is to increase the influenza vaccination rate among the elderly
      to 90%. Vaccination is the most effective measure for reducing the impact of
      influenza and is a cost-effective preventive health intervention for the elderly
      and individuals with chronic obstructive pulmonary disease.

PMID- 15847723
TI  - Human Metapneumovirus: An Important Cause of Respiratory Disease in Children and
      Adults.
AB  - Human metapneumovirus is a paramyxovirus that was discovered in 2001 in the
      Netherlands. Epidemiologic studies have shown it to be a major cause of acute
      respiratory tract disease in normal infants and children worldwide, with a
      seasonal occurrence and spectrum of clinical illness most similar to the closely
      related respiratory syncytial virus. The greatest prevalence of severe disease
      requiring hospitalization in otherwise healthy children appears to be in those
      aged between 6 and 12 months, older than the peak age of hospitalizations for
      respiratory syncytial virus. Human metapneumovirus is also a significant cause of
      acute respiratory disease in adults, particularly the elderly and those with
      comorbid conditions such as chronic obstructive pulmonary disease, asthma, and
      cancer. Because there is no rapid diagnostic assay, reverse transcriptase
      polymerase chain reaction is most widely used. Animal models have been developed,
      and candidate live-attenuated vaccines are in preclinical trials, offering the
      potential for future interventions in high-risk groups.

PMID- 15847724
TI  - Pneumococcal Vaccination in Adults.
AB  - Pneumococci remain the most common etiology of community-acquired pneumonia in
      adults, with significant attendant mortality in the elderly. With the recognition
      of increasing rates of drug-resistant Streptococcus pneumoniae in recent years,
      efforts to prevent disease through vaccination have gained greater impetus. The
      23-valent pneumococcal vaccine is used widely in the United States and provides
      effective protection against bacteremic pneumococcal disease, particularly in the
      immunocompetent host. The 7-valent pneumococcal conjugate vaccine, licensed in
      the United States in 2000, has had a dramatic impact on pneumococcal disease in
      the pediatric population, and its use in children has had effects on incidence
      rates in nonimmunized adults as well. Future directions include efforts to
      improve vaccination coverage in targeted populations and the development of more
      immunogenic and efficacious vaccines for high-risk groups.

PMID- 15847725
TI  - New HIV Drugs in Development, 2005.
AB  - Since the introduction of zidovudine 18 years ago, the treatment of HIV has been
      rapidly evolving. Current therapies target the HIV retrovirus successfully but
      contain their own perils. Active therapies with reduced adverse effects and long
      term activity in the presence of, or reduced susceptibility to, antiviral
      resistance continue to be needed. Furthermore, more convenient agents that may
      facilitate adherence to therapy are a goal of new drug development. This review
      addresses these clinical needs, with a discussion of several new drugs currently
      in the clinical trial pipeline.

PMID- 15847726
TI  - Non-AIDS-Defining Cancers and HIV Infection.
AB  - With fewer patients now succumbing to infectious complications of AIDS, other HIV
      related morbidities such as malignancies have become increasingly important.
      Apart from Kaposi's sarcoma, non-Hodgkin's lymphoma, and cervical cancer, which
      are considered as AIDS-defining, several additional cancers, referred to as non
      AIDS-defining cancers, are also statistically increased in HIV-infected persons.
      These include Hodgkin's disease, anal carcinoma, lung cancer, nonmelanomatous
      skin cancer, and testicular germ cell tumors, among others. However, the types of
      cancer observed at an increased frequency and the relative risks reported vary
      widely among studies. Although immunosuppression is consistently associated with
      an increased risk of AIDS-related malignancies, the role of immunosuppression in
      the pathogenesis of non-AIDS- defining cancers is controversial. Although data
      regarding the optimal management of these cancers are lacking, current studies
      suggest that patients with HIV-associated malignancies should be treated with
      similar approaches to those of their counterparts in the general population.

PMID- 15847727
TI  - [Functional ischemic mitral regurgitation: an open debate].
AB  - Functional ischemic mitral regurgitation is a complex disorder with a poor
      prognosis. Although the underlying anatomical and pathophysiological mechanisms
      are not entirely clear, it is known that postinfarction left ventricular
      remodeling is the most significant factor in the development of this mitral valve
      lesion. Echocardiography and magnetic resonance imaging have made significant
      contributions to clarifying the many mechanisms that progressively worsen mitral
      regurgitation. There is still controversy about the best surgical approach,
      particularly with regard to whether to replace or repair the valve, the type and
      size of prosthesis to be used in mitral annuloplasty, the durability of repair,
      valve-related complications, and medium-term survival. The early recurrence (< or
      =6 months) of mitral regurgitation after surgery has been reported in 17%-29% of
      patients. Better understanding of the origin and evolution of functional ischemic
      mitral regurgitation is necessary to enable the adoption of a more effective
      surgical approach to this enigmatic valvular disease.

PMID- 15847728
TI  - [Reperfusion treatment in an acute myocardial infarction in patients older than
      75 years. Do we need a randomized controlled trial?].

PMID- 15847729
TI  - [Hypertension in primary care. Are we aware of the magnitude of the problem and
      are we managing it properly?].

PMID- 15847730
TI  - [Characteristics and mortality following primary percutaneous coronary
      intervention for acute myocardial infarction in Spain. Results from the TRIANA 1
      (TRatamiento del Infarto Agudo de miocardio eN Ancianos) Registry].
AB  - INTRODUCTION AND OBJECTIVES: Although more elderly patients will experience acute
      myocardial infarction (AMI) in coming years, the best reperfusion strategy in
      these patients remains unknown. PATIENTS AND METHOD: The Spanish TRIANA
      (TRatamiento del Infarto Agudo de miocardio eN Ancianos) registry was set up to
      determine the feasibility of performing a randomized study of percutaneous
      coronary intervention (PCI) versus thrombolysis in AMI patients aged > or =75
      years. The TRIANA 1 subregistry included consecutive patients of all ages with ST
      segment-elevation AMI (< or =12 h from onset) who underwent PCI in selected
      hospitals. RESULTS: In total, 459 TRIANA-1 patients were included at 25 hospitals
      over 3 months. Some 11% had cardiogenic shock. PCI was performed as rescue
      therapy in 24% and, in 15% because thrombolysis was contraindicated. After PCI,
      83% had TIMI grade-3 flow without significant residual stenosis. Mortality at 1
      month was 10.8%. Independent predictors of mortality identified by multivariate
      analysis were: cardiogenic shock at admission (OR, 7.2, 95% CI, 2.2-23.3), age
      (OR, 1.05 per year, 95% CI, 1.005-1.100), maximum creatine kinase MB fraction
      (OR, 1.01, 95% CI, 1.004-1.270) and post-PCI TIMI grade <3 (OR, 2.8, 95% CI, 1.0
      8.3). Of 104 participants aged > or =75 years (mortality, 24%), 58 (55.7%)
      fulfilled criteria for inclusion in a randomized study. CONCLUSIONS: 1) The
      TRIANA 1 subregistry probably reflects the reality of PCI for AMI in Spain. 2)
      Mortality at 1 month was associated with classic predictive factors. 3) Some 50%
      of patients > or =75 years old who underwent PCI could be included in a
      randomized study. These findings indicate that randomized study to determine the
      best reperfusion strategy in elderly AMI patients is feasible.

PMID- 15847731
TI  - [Type of treatment and short-term outcome in elderly patients with acute
      myocardial infarction admitted to hospitals with a primary coronary angioplasty
      facility. The TRIANA (TRatamiento del Infarto Agudo de miocardio eN Ancianos)
      Registry].
AB  - INTRODUCTION AND OBJECTIVES: The nature and outcome of treatment for acute
      myocardial infarction in elderly patients admitted to Spanish hospitals with
      primary angioplasty facilities are not well documented. PATIENTS AND METHOD:
      Prospective analysis of registry data on patients > or =75 years old with ST
      segment-elevation acute myocardial infarction admitted between April and July
      2002 to Spanish hospitals with an active primary angioplasty program. RESULTS: We
      followed up 410 consecutive patients for 1 month. Their mean age was 80 (4.3)
      years and 46% were female. The median delay between symptom onset and arrival at
      hospital was 190 minutes. Around 42% of patients received no reperfusion therapy,
      35% were treated by thrombolysis, and 22% by primary angioplasty. Patients who
      underwent reperfusion therapy were younger, were more frequently male, had a
      shorter delay from symptom onset to hospital arrival, and had a better initial
      hemodynamic status (Killip Class). However, they were more likely to have
      extensive anterior infarctions. Overall, 30-day mortality was 24.9%. Independent
      predictors of death were age, systolic blood pressure, and Killip class >1, but
      not use of thrombolysis or primary angioplasty. CONCLUSIONS: Over 42% of elderly
      patients with myocardial infarction admitted to Spanish hospitals with
      angioplasty facilities did not receive reperfusion therapy. Thrombolysis was the
      most frequently used reperfusion therapy. However, neither thrombolysis nor
      primary angioplasty improved 30-day mortality.

PMID- 15847732
TI  - [Control of hypertension in elderly patients receiving primary care in Spain].
AB  - INTRODUCTION AND OBJECTIVES: Little information is available about the control of
      arterial hypertension in the elderly population. The aim of this study was to
      investigate hypertension control, factors associated with poor control, and
      general practitioners' responses to poor control in a large sample of
      hypertensive patients aged 65 years or older receiving primary care in Spain.
      PATIENTS AND METHOD: A cross-sectional study of elderly hypertensive patients
      taking antihypertensives was carried out. Blood pressure was measured in the
      standard manner. Blood pressure control was regarded as optimum if pressure
      averaged less than 140/90 mm Hg or, in diabetics, less than 130/85 mm Hg.
      RESULTS: The study included 5970 patients (mean age, 72.4 years; 62.8% women).
      Both systolic and diastolic blood pressures were well controlled in 33.5% of
      patients, systolic blood pressure alone in 35.5%, and diastolic blood pressure
      alone in 76.2%. Blood pressure control was found to be good more frequently when
      it was assessed in the evening (39.8%; P<.001), and when patients had taken
      treatment on the day of assessment (35.1%; P <.001). Some 12.9% of diabetics had
      pressures less than 130/85 mmHg and 9.7% had pressures less than 130/80 mmHg.
      General practitioners modified their therapeutic approach with only 17.2% of
      poorly controlled patients. CONCLUSIONS: Arterial blood pressure control was
      optimum in only three out of 10 Spanish hypertensive patients aged 65 years or
      older. Blood pressure control assessment was significantly influenced by surgery
      hours and by the timing of antihypertensive intake. General practitioners'
      therapeutic responses to poor control were too conservative.

PMID- 15847733
TI  - [Cardiovascular disease epidemiology and risk factors in primary care].
AB  - INTRODUCTION AND OBJECTIVES: To study the prevalence of and risk factors for
      cardiovascular disease in primary care. PATIENTS AND METHOD: A cross-sectional
      study was carried out at an urban health center in Barcelona, Spain. In total,
      2248 patients > or =15 years old were selected randomly from medical records. The
      study investigated cardiovascular diseases such as ischemic heart disease,
      cerebrovascular disease and peripheral arterial disease, and cardiovascular risk
      factors such as age, sex, smoking, high blood pressure, hypercholesterolemia,
      hypertriglyceridemia, and diabetes mellitus. RESULTS: The patients' mean age was
      49.1 (18.9) years and 53.5% were male. Cardiovascular risk factor prevalences
      were: smoking, 35.2%; high blood pressure, 33.7%; hypercholesterolemia, 21.9%;
      hypertriglyceridemia,12.7%; and diabetes mellitus, 15.8%. Overall, 57.9% of
      patients had at least 1 cardiovascular risk factor. Significantly more males
      presented with each risk factor (P<.05), apart from high blood pressure. The
      prevalence of all risk factors, except smoking, increased with age until 74 years
      and then stabilized, except high blood pressure, which continued to increase.
      Around 10% had cardiovascular disease, with myocardial ischemia in 5.5%,
      cerebrovascular disease in 3.7%, and peripheral arterial disease in 2.4%. All
      except cerebrovascular disease were significantly more common in males (P<.05).
      The prevalence of cardiovascular disease was low in individuals <55 years old,
      particularly women, and increased with age for all forms of disease. Some 68.3%
      were > or =65 years old. CONCLUSIONS: The high prevalence of cardiovascular risk
      factors was confirmed. Cardiovascular disease was more common in males and the
      elderly.

PMID- 15847734
TI  - [Reduction in heart failure hospitalization rate during the first year of follow
      up at a multidisciplinary unit].
AB  - INTRODUCTION AND OBJECTIVES: Heart failure leads to frequent hospital
      readmissions. The aim of this study was to assess how receiving attention at our
      multidisciplinary unit influenced hospitalization for heart failure. We compared
      the number of admissions in the year preceding attendance with that in the first
      year of follow-up. PATIENTS AND METHOD: In total, 366 patients were admitted
      between August 2001 and June 2003. Of these, 332 were still alive and could be
      assessed clinically 1 year later. The most common etiologies were ischemic heart
      disease in 60%, and dilated cardiomyopathy in 10%. RESULTS: The number of
      admissions in the year preceding attendance was 246, while that during the first
      year of follow-up was 125, which corresponds to a statistically significant
      reduction of 49% (P<.001). The reduction was even greater (54%, P<.001), when
      only patients who were hospitalized more than once in the preceding year were
      analyzed. Moreover, in addition to the improvements noted during follow-up in
      patients' understanding of the disease and in several aspects of self-care, the
      increase in treatment use was also remarkable: beta-blocker use increased from
      53% to 70%, spironolactone use from 20% to 30%, and statin use from 36% to 58%.
      CONCLUSIONS: The number of hospital admissions for heart failure among patients
      who received attention at our multidisciplinary unit was significantly less in
      the first year of follow-up than in the year preceding attendance. This reduction
      was probably due to educational and pharmacologic interventions and to closer
      follow-up.

PMID- 15847735
TI  - [Long-term trends in drug prescription for hospitalized patients with congestive
      heart failure. Influence of type of dysfunction].
AB  - INTRODUCTION AND OBJECTIVES: To evaluate changes in drug prescription during 1991
      2002 in patients hospitalized for congestive heart failure (CHF) with preserved
      or depressed left ventricular (LV) systolic function. PATIENTS AND METHOD: A
      total of 1252 CHF patients (mean age, 69.4 (11.7) years; 61.3% male) hospitalized
      in a cardiology department were studied. Ischemic heart disease was present in
      616 (49.2%), hypertension in 693 (55.4%), and diabetes in 335 (26.8%). Some 498
      (39.8%) had preserved LV systolic function, defined as an echocardiographically
      determined ejection fraction > or =50% at admission. Pharmacotherapy at hospital
      discharge was recorded for all patients. RESULTS: The changes in drug
      prescription observed in CHF patients with preserved LV systolic function
      paralleled those in patients with depressed LV systolic function. Change was
      influenced by the publication of major clinical trials on CHF and depressed LV
      systolic function. Consequently, the use of angiotensin-converting enzyme
      inhibitors, angiotensin-receptor blockers, beta-blockers, and spironolactone
      progressively increased during follow-up for both types of CHF. Diuretics were
      prescribed for more than 70% of patients, with the rate being higher in those
      with depressed LV systolic function. Digoxin use decreased markedly in patients
      with preserved LV systolic function. CONCLUSIONS: An increase in the prescription
      of drugs with proven effects on mortality and morbidity in patients with CHF was
      observed. Nevertheless, beta-blocker and spironolactone use remains suboptimal.
      The trend seen after hospitalization in CHF patients with preserved LV systolic
      function was similar, though slightly less marked.

PMID- 15847736
TI  - [Executive summary of the guidelines on the diagnosis and treatment of acute
      heart failure].

PMID- 15847737
TI  - [Influence of clinical and anatomical factors on the outcome of percutaneous
      coronary interventions].
AB  - The outcome of percutaneous coronary interventions depends on several factors.
      Some relate to the patient's clinical characteristics, in particular, to the
      presence of diabetes, renal failure, or unstable syndromes, the number of
      diseased vessels, and the level of left ventricular function. Others are linked
      to the anatomical characteristics of the lesion. Firstly, whether it is located
      in the left main coronary artery or in a coronary ostium, whether there is a
      saphenous vein graft, and whether the lesion is bifurcated or involves small
      diameter arteries. Secondly, whether lesion morphology is characterized by heavy
      calcification or severe occlusion. Therapy using coronary stents has become the
      standard approach. Angiographically, results are good but some problems occur
      over the long term, such as restenosis. The recent introduction of stents coated
      in drugs that inhibit intimal proliferation, which have been shown to reduce the
      restenosis rate dramatically, is certain to increase and alter the range of
      applications of percutaneous coronary interventions.

PMID- 15847738
TI  - [Reflex transient atrioventricular block during atrial fibrillation ablation].

PMID- 15847739
TI  - [Cardiac involvement in Kearns-Sayre syndrome].
AB  - The mitochondrial cytopathies or oxidative-phosphorylation diseases are a diverse
      group of disorders that result from the structural, biochemical, or genetic
      derangement of mitochondria. Because mitochondrial dysfunction can affect the
      most highly energy-dependent organs, cardiac involvement is frequent in these
      diseases. To identify the clinical features of Kearns-Sayre syndrome, an entity
      associated with this group of diseases, we evaluated cardiac structure and
      function in 5 patients with Kearns-Sayre syndrome and followed the clinical
      course of these patients for 5 years.

PMID- 15847740
TI  - [Multiple pulmonary nodules and amiodarone. KL-6 as a new diagnostic tool].
AB  - Pulmonary toxicity is an infrequent but serious adverse event in patients treated
      with amiodarone. The main problem at present is that we lack the necessary tools
      to detect this event or predict which patients will develop pulmonary toxicity.
      Serum Krebs von den Lungen-6 (KL-6) has been previously recognized as a marker
      for the activity of diffuse interstitial lung disease. We describe a patient with
      pulmonary toxicity due to amiodarone with increased blood levels of this new
      marker, and discuss the clinical usefulness of this new diagnostic tool.

PMID- 15847741
TI  - [Cardiac hamartoma. Case report and literature review].
AB  - Primary cardiac tumors are infrequent and usually benign. They can manifest as
      dyspnea, chest pain, palpitations, sudden death, peripheral embolism, cyanosis,
      or general symptoms. They are sometimes an incidental finding in an asymptomatic
      patient. We describe a 33-year-old man who was seen because of dyspnea and
      palpitations. Transthoracic echocardiography revealed, on the lateral wall of the
      left ventricle, an intramyocardial mass that was successfully resected
      surgically. The pathologic diagnosis was hamartoma of mature cardiac myocytes. We
      discuss the usefulness of imaging techniques for identifying cardiac masses.

PMID- 15847742
TI  - [Pulmonary hemorrhage after abciximab. Risk factors and the role of protamine].
AB  - Large clinical trials have demonstrated the clinical effectiveness of therapy
      with inhibitors of the platelet surface-membrane glycoprotein IIb-IIIa receptor
      in a broad range of patients with ischemic heart disease. Abciximab, a platelet
      glycoprotein IIb-IIIa receptor blocker, is associated with improved long-term
      prognosis in patients who require angioplasty and stent placement. Severe
      bleeding from abciximab use is an uncommon event. We describe a patient with
      severe pulmonary hemorrhage after treatment with abciximab, and discuss
      predisposing factors and protamine infusion in this potentially fatal
      complication.

PMID- 15847743
TI  - [Intracardiac sewing needle in a women with autoaggressive behavior].

PMID- 15847744
TI  - [Invasive treatment of non-ST-segment elevation acute coronary syndrome: is there
      more than one real world?].

PMID- 15847745
TI  - [Vacuum-assisted therapy for mediastinitis after heart transplantation].

PMID- 15847747
TI  - [Hyperhomocysteinemia and treatment with antiepileptic drugs. Effects of
      different doses of folic acid].
AB  - BACKGROUND AND OBJECTIVE: An increase homocysteine values, which is an
      independent risk factor for atherotrombotic disease, can be produced with
      antiepileptic treatment. The aims of this study were: 1) to assess the frequency
      and determinant factors of hyperhomocysteinemia in adult patients receiving
      antiepileptic drugs, and 2) to know the effect of different doses of folic acid.
      PATIENTS AND METHOD: Ninety eight patients and 100 healthy controls similar in
      age and gender were studied. Eighty six patients were treated with hepatic enzyme
      inductors (diphenylhydantoine and/or phenobarbital and/or primidone and/or
      carbamazepine), 5 received non inductors (valproate) and 7 were treated with both
      in combination. Thirty eight patients were randomized to receive in an open and
      concurrent way folic acid, 0.2 mg (n = 18) or 5.2 mg (n = 20) daily for 3 months.
      RESULTS: Homocysteine values were increased in patients in relation with controls
      (mean [SD]12.2 [6.7] 95% confidence interval [CI],10.0-13.5 vs 8.8[2.2] 95% CI,
      8.3-9.2 micromol/l; p < 0.001). Hyperhomocysteinemia was found in 28 patients and
      4 controls (28.6% vs 4.0%; p < 0.001). In a multivariate analysis
      hyperhomocysteinemia was positively associated with treatment with antiepileptic
      inductors and negatively with folate values and female gender. Homocysteine
      values decreased after treatment with folic acid at high and low doses (p < 0.001
      for both groups), and the values observed in the latter group were similar to
      those in healthy controls. CONCLUSIONS: Hyperhomocysteinemia is frequent in
      patients treated with antiepileptic drugs. Treatment with hepatic enzyme
      inductors and low folate values are predictors of hyperhomocysteinemia.
      Administration of folic acid, even at very low doses, produces a significant
      decrease of homocysteinemia in these patients.

PMID- 15847748
TI  - [Clinical-epidemiological characteristics and antiretroviral treatment trends in
      a cohort of HIV infected patients. The PISCIS Project].
AB  - BACKGROUND AND OBJECTIVE: The aims of this study were to describe the process of
      implementation of the PISCIS cohort, and to describe the clinical and
      epidemiological characteristics and trends of antiretroviral treatment (ART)
      among patients enrolled from 1998 through 2003. PATIENTS AND METHOD: Prospective
      cohort study of HIV-infected patients aged > or = 16 years newly attended in 10
      Catalonian hospitals and one Balearic Islands hospital. Analysis were done using
      the Mantel's chi2 test for trend. RESULTS: A total of 5,968 patients (mean age 39
      yrs; 75% men) were recruited with a mean follow-up of 26.4 months (13,130 person
      years). A total of 2,763 patients were newly diagnosed and among these, the most
      frequent transmission route was the heterosexual one (43%), followed by
      homosexual (31%). We observed an increasing trend in the proportion of persons <
      35 years and immigrants. Among newly diagnosed, 43% had < 200 CD4 T cells/microl
      in the nearest determination from HIV diagnosis. In the year 2003, 83% of
      patients were on ART. A decrease of the protease inhibitor-based regimen (from
      85% in 1998 to 25% in 2003; p < 0.001) and an increase of nucleoside and non
      nucleoside analogue reverse transcriptase inhibitors-containing regimens were
      observed over time among naive patients who started ART with three or more drugs.
      CONCLUSIONS: HIV infected patients' cohorts are feasible in our setting and are
      an important tool in clinical and public health. The heterosexual route of
      transmission was the most frequent among newly diagnosed patients. The diagnosis
      delay is high and, on the other hand, ARV regimens have been changing according
      to the recommended guidelines.

PMID- 15847749
TI  - [Effect of hyperhomocysteinemia and methylenetetrahydrofolate reductase 677C -->
      T mutation in venous thromboembolism risk of young adults].
AB  - BACKGROUND AND OBJECTIVE: To investigate whether hyperhomocysteinemia and
      methylenetetrahydrofolate reductase (MTHFR) 677C --> T mutation are associated
      with venous thromboembolism in young Spanish adults. PATIENTS AND METHOD: One
      hundred adult patients younger than 50 years and 177 controls with similar age
      and gender. RESULTS: Hyperhomocysteinemia was present in 21% of the patients and
      3.3% of the controls (p < 0.001), and MTHFR 677C --> T mutation was found in 25
      and 14.7%, respectively (p = 0.03). Odds ratio (OR) for thromboembolism in
      hyperhomocysteinemic patients was 7.5 (95% CI, 2.9-19.2; p < 0.001), and in
      patients with MTHFR 677C --> T mutation the OR was 1.9 (95% CI, 1.1-3.5; p =
      0.03). In a subgroup of 76 patients without other thrombogenic factors,
      thromboembolism persisted associated with hyperhomocysteinemia, yet an
      association with MTHFR 677C --> T mutation was not confirmed. CONCLUSIONS:
      Hyperhomocysteinemia, but not MTHFR 677C --> T mutation, is a risk factor for
      venous thromboembolism in young adults without other thrombogenic factors.

PMID- 15847750
TI  - [Predisposing factors of delirium in hip fractured patients older than 84 years].
AB  - BACKGROUND AND OBJECTIVE: Our objective was to analyze those factors predisposing
      to delirium in patients older than 84 years who were admitted because of hip
      fracture. We also compared the prevalence of delirium in this population with a
      younger group. PATIENTS AND METHOD: One hundred and thirty patients (mean age
      91.8 years) and 50 controls aged 65 to 84 years were included. RESULTS: Forty
      three patients (33%) developed delirium. A poor previous functional capacity was
      the best marker identifying those at risk for developing delirium. Although the
      prevalence of delirium was higher in those older than 84 years, statistically
      significant differences were not reached. CONCLUSIONS: Disability prior to
      admission is the main risk factor predisposing to delirium during hospitalization
      in patients older than 84 years who are admitted because of hip fracture.

PMID- 15847751
TI  - [Delirium in hospitalized elderly patients].

PMID- 15847752
TI  - [Homocysteine and low dietary intake: two complementary forms of impairment
      (correction of improvement)].

PMID- 15847753
TI  - [Determination and utilisation of the plasmatic concentration of homocysteine in
      clinical practice].
AB  - Homocysteine is a methionine-derived amino acid and its metabolism depends on
      B12, B6 and B2 vitamins and folic acid. The total homocysteine plasmatic
      concentration can be measured in most laboratories by means of
      enzymeimmunoassays. Hyperhomocysteinemia may be caused by genetic defects of the
      enzymes involved in its metabolism, nutritional deficiencies or absorption
      deficiencies of the vitamin cofactors of these enzymes, chronic diseases or
      administration of some drugs. An increase in the total plasmatic concentration of
      homocysteine represents a sensitive marker of folate and cobalamin deficiencies
      as well as an independent risk factor of cardiovascular disease. Furthermore,
      total plasmatic concentrations of homocysteine are related to the development of
      congenital malformations, pregnancy complications, psychiatric diseases and to
      cognitive impairment in the elderly. Therefore, the measurement of the
      concentration of homocysteine has a notable clinical interest, which may increase
      in future if it is confirmed that the association with these disorders is causal
      and that they can be prevented by treating hyperhomocysteinemia.

PMID- 15847754
TI  - [Burnout in professionals belonging to palliative, intensive care and emergency
      services in a general hospital].

PMID- 15847755
TI  - [Should patients and/or their representatives be involved in the design and
      fulfillment of informed consent documents in the ICU].

PMID- 15847756
TI  - [Unusual increment of congenital hypothyroidism cases in Cantabria (Spain): a
      case-control study].

PMID- 15847757
TI  - [Influence of the proximity of death on the priority of the factors that can help
      people to have a good death].

PMID- 15847758
TI  - [High percentage of influenza vaccination in nonagenarian patients after an
      educational programme].

PMID- 15847759
TI  - [Acute pancreatitis due to salmonella enteritidis infection].

PMID- 15847760
TI  - [Left ventricular dysfunction associated with Behcet disease].

PMID- 15847761
TI  - [Applicability of the clinical trials outcomes in heart failure to older people].

PMID- 15847762
TI  - [Intestinal tuberculosis in a patient with idiopathic CD4+ T-lymphocytopenia].

PMID- 15847764
TI  - Safety, effectiveness, and patterns of use of olanzapine in acute schizophrenia:
      a multivariate analysis of a large naturalistic study in the hospital setting.
AB  - BACKGROUND AND OBJECTIVE: This study assessed the safety and effectiveness of the
      atypical antipsychotic olanzapine for the treatment of inpatients with acute
      schizophrenia. Furthermore, we evaluated patterns of use of olanzapine and their
      relationship to safety and effectiveness. PATIENTS AND METHOD: This was a
      prospective, comparative, nonrandomized, open-label, observational study of 848
      patients with schizophrenia (International Classification of Diseases, 10th
      edition) hospitalized due to an acute psychotic episode. Data were collected
      during patients' entire hospital stay. Safety of antipsychotic therapy was
      assessed with an extrapyramidal symptoms questionnaire (based on the Udvalg for
      Kliniske Undersogelser scale) and the report of spontaneous adverse events.
      Clinical status was assessed with the Brief Psychiatric Rating Scale (BPRS) and
      the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate
      statistical approach was employed. RESULTS: Patients treated with olanzapine in
      monotherapy had the lowest risk of developing extrapyramidal symptoms (11.2%),
      whereas patients treated with conventional antipsychotics had a higher risk
      (39.0%; p < 0.001). Patients treated with olanzapine in monotherapy (even
      patients with prominent positive symptoms) displayed a higher rate of response
      compared with conventional antipsychotics-treated patients (p = .007).
      CONCLUSIONS: Olanzapine is a safe and effective treatment for patients with acute
      schizophrenia in the hospital setting, even for patients with prominent positive
      or agitation symptoms.

PMID- 15847765
TI  - [The application of the SCORE charts to advanced age males triple the number of
      high-risk subjects compared to the Framingham function].
AB  - BACKGROUND AND OBJECTIVE: The Framingham function, recommended by the National
      Cholesterol Education Program in its document Adult Treatment Panel III (ATP
      III), and the risk charts of the Systematic Coronary Risk Evaluation (SCORE)
      program are the most used functions for risk stratification. In both, intensive
      hygienic and therapeutic measures are recommended for high risk individuals. The
      objective of the present study was to compare the risk stratification obtained
      with both functions in a population of subjects older than 60 years. SUBJECTS AND
      METHOD: 1001 non-diabetic subjects between 60 and 79 years old (mean: 69 years,
      67% female) with no evidence of cardiovascular disease were included in the
      study. Participants were classified as low, moderate or high risk by ATP-III (<
      10%, 10-20% y > 20% of risk at 10 years, respectively) and by SCORE (< 3%, 3-4% y
      > or = 5% of risk at 10 years respectively). RESULTS: 11.7% of the population was
      classified as high risk by Framingham and 17.6% by SCORE. Only 5% of the females
      were classified as high risk with either function. In males, 16.7% and a 44.4%
      were classified as high risk by Framingham and SCORE respectively. The results
      did not differ by age group. A 39% of males and a 20% of females were candidates
      to hypolipidemic treatment as recommended by SCORE guidelines. CONCLUSIONS:
      Compared to Framingham function, the application of SCORE charts to spanish males
      over 60 years triplicate the number of high risk individuals and candidates to
      intensive risk factor treatment.

PMID- 15847766
TI  - [Prognostic factors of clinical outcome of the tuberculous pleural effusion].
AB  - BACKGROUND AND OBJECTIVE: To date, no studies have been reported analyzing the
      prognosis factors related to severe clinical complications in tuberculous pleural
      effusion (TPE). We studied clinical, biochemical, radiological, and
      microbiological factors that could help establish the clinical outcome of TPE.
      PATIENTS AND METHOD: Retrospective study of > or = 15 years old patients
      diagnosed of TPE along 9 years. Patients were classified in two groups: a group
      without complications (NCG), and a group with complications (CG) on the basis of
      residual pleural thickening (RPT) > or = 10 mm, need of surgery or death.
      RESULTS: Sixty six patients were included, mean age 35.3 years, 53% male, 47 in
      the NCG group and 19 in the CG (1 died, 4 needed surgery, 14 had RPT). The
      evolution of clinical symptoms was 20.7 days in the NCG and 45.6 in the CG. 94.7%
      of the CG patients had loculations (23.4% in the NCG). We observed significant
      differences in the pH (7.34 vs 7.11), glucose (78 vs 30 mg/dl) and lactic
      dehydrogenase (925 vs 3,235 U/l). CONCLUSIONS: Severe TPE has similar
      characteristics to complicated parapneumonic pleural effusion. Loculations, pH <
      7.25 and glucose < 50 mg/dl were indicative of a poorly outcome in our study.

PMID- 15847767
TI  - [Sequelae of tuberculous pleural effusion].

PMID- 15847768
TI  - [Asthma: control as therapeutic goal].

PMID- 15847769
TI  - [University of Health Sciences: legal aspects of a new option].

PMID- 15847770
TI  - [Therapeutic applications of stem-cells].
AB  - In the last years stem cells (SC) have generated huge expectations and have
      become a new hope for the development of novel cell therapies in the context of
      regenerative medicine. So far, the hypothetic therapeutic effects of SC, both of
      embryonic and adult origin, have been demonstrated only in a very few cases.
      Embryonic SC are pluripotential and have, in theory, more plasticity to
      differentiate into a wide range of cell or tissue types. However, the society
      still has to decide on the ethics of its use. Regarding adult SC, they are
      readily available and are fully matched. However, whether their potential will
      translate into therapeutic benefits in humans needs to be determined as yet. This
      article is intended to give a general overview on this field, based on the
      current scientific knowledge.

PMID- 15847771
TI  - [Efficacy of pediculicidal drugs in pediculosis capitis].

PMID- 15847772
TI  - [Breast angiosarcoma after conservative treatment for breast carcinoma].

PMID- 15847773
TI  - [Antihypertensive therapy and congestive heart failure].

PMID- 15847775
TI  - [Complete resolution of chronic hydrocephalus of adult with acetazolamide].

PMID- 15847776
TI  - [Efficacy of therapy with anti-CD20 antibody (rituximab) in a patient with
      autoimmune hemolytic anemia associated].

PMID- 15847777
TI  - [Acute pericarditis].

PMID- 15847779
TI  - [Antiphospholipid antibodies induced by Chlamydia pneumoniae infections].

PMID- 15847781
TI  - [We continue with continuing education].

PMID- 15847782
TI  - [Application of recombinant human TSH in the diagnostic protocol of
      differentiated thyroid carcinoma].
AB  - OBJECTIVES: To describe the preliminary results of the application of this new
      technique in the diagnostic protocol in the management of differentiated thyroid
      cancer (DTC). MATERIAL AND METHODS: 131I Whole body scan (WBS) was made under
      rhTSH stimulation in a group of 102 patients with DTC in follow-up, all treated
      by means of total thyroidectomy. The administration guideline was a dose of 0.9
      mg of rhTSH (intramuscular) for two consecutive days, followed by oral activity
      of 185 MBq of 131I 24 hours after the last rhTSH injection, and later
      scintigraphic scan after 48 hours of the administration of 131I. Serum samples
      for TSH, thyroglobulin and antithyroglobulin antibodies determination were
      collected at 24 and 72 hours of the last administration of the rhTSH. Measures
      were made by means of immunometric assays. RESULTS: TSH values at 24 hours after
      exogenous stimulation were 147.54 +/- 46.46 mIU/l. In 62 patients values of
      negative Tg were obtained (< 1 ng/ml), 50 of which presented negative WBS and 12
      positive. 37 patients had positive Tg, 17 of whom presented negative WBS
      (confirming presence of disease in 7 patient by means of other imaging
      techniques) and 20 positive. CONCLUSIONS: In every case, administration of rhTSH
      produced a significant increase of the TSH, making it possible to perform the
      usual controls of patient management (determination of serum Tg and WBS),
      similarly to the hormone withdrawal situation. There is no evidence of
      significant side effects, and its use makes it possible to avoid disadvantages
      derived from the hormonal withdrawal, maintaining a good quality of life in
      patients.

PMID- 15847783
TI  - [Meta-analysis of the diagnostic efficacy of FDG-PET in patients with suspected
      ovarian cancer recurrence].
AB  - AIM: The aim of this paper was to perform a meta-analysis of the literature to
      evaluate the accuracy of FDG-PET in recurrence detection in patients with ovarian
      cancer. METHODS: The search strategy consisted in identifying papers published
      between November 1972 and October 2003 indexed in MEDLINE and CANCERLITE.
      Inclusion criteria were publications that evaluated recurrence with FDG-PET in
      patients with ovarian carcinoma. Exclusion criteria were duplicated papers or
      those outdated by subsequent ones. The statistical analysis included 95 %
      confidence intervals (CI) of sensitivity (S), specificity (Sp) and natural
      logarithm of the odds ratio (Ln OR). RESULTS: Seventeen publications fulfilled
      the inclusion criteria and were analyzed. The S and Sp were 0.94 (95% CI, 0.93
      0.96) and 0.65 (95% CI, 0.46-0.85), respectively. The Ln OR presented global
      homogeneity and significant values in > 75% of the studies. CONCLUSION: According
      to our meta-analysis, FDG-PET has high S and intermediate Sp, with few false
      negative results. These preliminary findings suggest that FDG-PET may be an
      effective means of identifying patients with recurrent ovarian cancer.

PMID- 15847784
TI  - [Positive exercise test and normal exercise myocardial perfusion SPECT. Clinical
      significance].
AB  - OBJECTIVE: To establish, in our area, the clinical significance of a normal
      exercise myocardial perfusion study, in patients with an ischemic response of the
      exercise test. MATERIAL AND METHODS: A retrospective study was carried out in our
      Service for the last four years. We studied 45 patients (41 women and 4 men) with
      an ischemic response of the exercise test and normal myocardial perfusion SPECT,
      during a mean follow-up of 13,2 months. We considered the final clinical
      diagnosis according to clinical evolution, therapy outcome and coronary
      angiography results. RESULTS: The presence of positive exercise test and normal
      SPECT was predominant in women (93.3%). In 35 patients (77.8%), the final
      diagnosis was chest pain of probable non-coronary origin (not secondary to
      coronary artery disease): 18 patients were diagnosed of hypertensive
      cardiomyopathy, 3 of valvulopathy, 2 of vasospastic angina, 1 of hypertrophic
      obstructive cardiomyopathy, 1 of microvascular angina, 1 of angina due to
      arrhythmia, and 9 patients diagnosed of atypical chest pain due to functional or
      non-cardiac origin. In 10 patients (22.2%), the final diagnosis was chest pain of
      probable coronary origin. We did not observe any major cardiac events (cardiac
      death and nonfatal myocardial infarction) during the follow-up period.
      CONCLUSIONS: Patients with chest pain, positive exercise test and normal SPECT
      have an excellent prognosis within an intermediate follow-up period. 77.8% of
      patients were diagnosed of chest pain of non-coronary origin. The most common
      cause of non-coronary chest pain was hypertensive cardiomyopathy (51.4%),
      followed by functional or non-cardiac chest pain (28.6%).

PMID- 15847785
TI  - [Cytosolic pS2 levels and cellular proliferation in ER-positive and PgR-positive
      infiltrating ductal carcinomas of the breast].
AB  - OBJECTIVE: The trefoil factor 1 (TFF1/pS2) is an estrogen-induced molecule in
      breast tumours. We wanted to study its expression in ER+ and PgR+ infiltrating
      ductal carcinomas of the breast (IDCs), and to correlate it with other clinical
      biological parameters and the outcome. MATERIAL AND METHODS: Cytosolic pS2 levels
      were measured using an IRMA (CIS. Biointernational. France) in 170 tumors.
      Likewise we determined the cytosolic levels of cathepsin D and tissue-type
      plasminogen activator (t-PA), as well as the concentrations of the epidermal
      growth factor receptor (EGFR), erbB2 oncoprotein, CD44v5 and CD44v6 on cell
      surfaces. Also the tumour size, histological grade (HG), axillary lymph node
      involvement, distant metastasis, ploidy, DNA index and of cellular synthesis
      phase (SP) was taken in account. RESULTS: The pS2-positive (> 5 ng/mg prot.)
      tumours showed higher concentrations of cathepsin D (p: 0.0043) and t-PA (p:
      0.0089) than the pS2-negative ones. Likewise, they were less frequently HG3 (p:
      0.0231), SP > 7 % (p: 0.0005) and SP > 14% (p:0.0014). During the follow-up time
      (r: 1-147; 50,1+/-31,7; median 37 months) the pS2-positive tumors showed a less
      number of recurrences (5/101 vs 6/69; p: 0.059) but not of deaths by the tumor
      (1/101 vs 2/69). CONCLUSIONS: These results support an inverse relationship
      between pS2 positivity and cellular proliferation in IDCs and suggest a new role
      of this protein (different of the hormone dependence) in the biology of these
      breast carcinomas, while further studies will be required to establish the impact
      of this finding on their outcome.

PMID- 15847786
TI  - [Uptake of 123I-MIBG in a hepatic hemangioma in the scintigraphic study of an
      adrenal gland lesion].
AB  - A 60 year old symptom free female in whom a lesion in left adrenal gland was
      found by chance in a CT scan is presented. She also had increased serum and urine
      catecholamines levels. 123I-MIBG scintigraphy showed a non-physiological uptake
      in right adrenal gland that is still seen in the delayed image, with normal left
      gland. MRI confirmed the presence of a mass in the left adrenal gland suggestive
      of an adenoma and found a lesion in the right hepatic area at the level of the
      previously seen MIBG image. This lesion was labelled as a hemangioma and would
      explain the findings of the isotopic study with MIBG. It must be considered as a
      false positive for phaechromocytoma. The increased catecholamine serum and urine
      levels were due to drug interactions.

PMID- 15847787
TI  - [Progressive myositis ossificans. Utility of bone scintigraphy].
AB  - 47 year old woman affected by myositis ossificans, with muscular calcifications
      in her evolution. Bone scintigraphy showed increased polyfocal activity as well
      as uptake of different intensity in soft tissues. The bone scintigraphy allows
      for early identification of ossification areas in soft tissues, as it can even
      detect injuries earlier than that observed with other image techniques. It is
      considered to be very useful in the diagnosis and establishment of the extension
      of the process, as well as follow-up.

PMID- 15847788
TI  - [99mTc-HMPAO brain SPECT in a case of HSV encephalitis].
AB  - We present a case of encephalitis caused by Herpes Simplex Virus in a 57 year old
      woman. The acute picture was suggestive of viral infection without associated
      neurological symptoms. Due to the posterior appearance of neurological focality,
      cerebral spinal fluid (CSF) was analyzed. It showed pleocytosis and
      lymphocytosis, inflammatory process data, and serological test with positivity
      for Simple Herpes Virus (SHV) subtypes I and II. During admission, other
      complementary tests were performed: EEG, CT, MRI, cerebral perfusion SPECT; the
      later supplied significant data regarding anatomical neuroimaging (CT, MRI) in
      regards to bihemispheral extension of the encephalic condition. Furthermore,
      after clinical discharge, persistent metabolic abnormality was demonstrated in
      temporal cortex, responsible for concomitant mixed aphasia.

PMID- 15847789
TI  - [Scrotal defect on bone scintigraphy].

PMID- 15847790
TI  - [PET-FDG study in a patient with history of uterine leiomyosarcoma during
      menstruation and a false positive result].

PMID- 15847791
TI  - [Controversies in the follow-up and management of well-differentiated thyroid
      cancer. New answers to old questions].

PMID- 15847792
TI  - Identification of naturally secreted soluble form of TL1A, a TNF-like cytokine.
AB  - TL1A, a TNF-like ligand, mediates signaling via its cognate receptor DR3, a death
      receptor whose activation was known to induce both death and survival factors.
      TL1A, like TNF, is also presumed to circulate as a homotrimeric soluble form. To
      identify soluble TL1A in the immune system, we have developed a quantitative
      ELISA by pairing a monoclonal antibody (MAb) with a biotinylated anti-TL1A
      polyclonal antibody (PAb) as capture and detection antibodies, respectively. The
      assay had a detection limit of 32 pg/ml. Overnight culture of human umbilical
      vein endothelial cells (HUVEC) expressed up to 160 pg/ml of TL1A, and that
      proinflammatory cytokines, IL-1 and TNF, significantly increased TL1A mRNA and
      soluble protein up to several folds in contrast to IL-6 and IL-11, which induced
      neither protein nor mRNA in the cells. IL-1 appeared to be a better stimulator of
      TL1A than TNF-alpha, and the induction of soluble TL1A in HUVEC in response to IL
      1 was dose and time-dependent. We have also purified soluble TL1A from a large
      volume of IL-1 stimulated HUVEC conditioned medium using an anti-TL1A PAb-coupled
      affinity column. The protein eluted from the column was further reacted with anti
      TL1A MAbs in Western blot: 30-kDa and 32-kDa under non-reducing and reducing
      conditions, respectively. Taken together, our results indicated that ELISA might
      be useful in studying soluble TL1A regulation in certain inflammatory conditions.

PMID- 15847793
TI  - Production of recombinant Ig molecules from antigen-selected single B cells and
      restricted usage of Ig-gene segments by anti-D antibodies.
AB  - The Ig-genes of the heavy chains in anti-D-specific hybridomas and Fab/scFv
      fragments selected from phage-display libraries are restricted to a group of
      closely related genes (IGHV3s genes). We analyzed the Ig-gene repertoire in anti
      D-specific B cells of two hyperimmunized donors using a completely different
      method. Single B cells were cultured for 10 days in an EL4.B5 culture system.
      mRNA from anti-D-producing B cells was reverse transcribed into cDNA. Heavy- and
      light-chain gene rearrangements were amplified by PCR reactions, sequenced and
      cloned into a pNUT-vector system, thereby allowing the production of complete IgG
      and IgM. Eleven anti-D-specific B-cell clones were isolated and analyzed. Eight
      of these clones (including IgM-producing clones) had IGHV3s genes. We
      demonstrated that functional anti-D-specific IgM (4 clones) and IgG (2 clones)
      was produced. Using a new method, we analyzed the IGHV gene repertoire of anti-D
      specific B cells of hyperimmunized donors and showed that it is indeed
      restricted. Moreover, we found a high frequency (1:100 and 1:500) of anti-D
      specific B cells in the peripheral B cells of hyperimmunized donors. We suggest
      that this approach could be applied for the selection of human mAbs from
      immunized donors and for the analysis of Ig-gene repertoires at the single-B cell
      level.

PMID- 15847794
TI  - Expression mapping using a retroviral vector for CD8+ T cell epitopes: definition
      of a Mycobacterium tuberculosis peptide presented by H2-Dd.
AB  - Identification of CD8+ T cell epitopes is important because detection of specific
      CD8+ T cells after infection or immunization requires prior knowledge of epitope
      specificity. Furthermore, identification of CD8+ T cell epitopes permits the
      development of specific preventive and therapeutic approaches to both infections
      and tumors. Thus far, CD8+ T cell epitopes have been identified either using an
      overlapping peptide library covering an entire protein, or using algorithms
      designed to identify likely peptides that bind to major histocompatibility
      complex (MHC) class I molecules. The synthesis of overlapping peptides can be
      prohibitively expensive, and the algorithm programs used to predict CD8+ T cell
      epitopes are not always accurate. Here we describe a retroviral expression system
      that specifically allows longer polypeptides and shorter peptides to be expressed
      in the cytoplasm, and thereby to be processed onto class I MHC molecules. T cells
      from mice that were immunized with a DNA vaccine encoding MPT-51 were probed
      against MHC-compatible cell lines retrovirally transduced with overlapping gene
      fragments encoding 120-140 amino acids of the MPT-51 molecule. After further
      testing of shorter peptide sequences, we identified a CD8+ T cell epitope using
      cell lines expressing a relatively small number of algorithm-predicted candidate
      epitopes. We found that one of the requirements for cell surface display of the
      20-mer peptide was the need for cotranslational ubiquitination. The restriction
      molecule was identified as Dd following transduction with MHC class I genes
      followed by transduction with the oligonucleotide encoding the epitope. The
      retroviral expression system described here is cost-effective, particularly if
      the target molecule is large, and could be adapted to identifying T cell epitopes
      recognized in infectious disease and against tumor cell antigens.

PMID- 15847795
TI  - Complexes between C1q and C3 or C4: novel and specific markers for classical
      complement pathway activation.
AB  - Classical pathway activation is often assessed by measuring circulating levels of
      activated C4. However, this parameter does not discriminate between activation
      through the classical or the lectin pathway. We hypothesized that during
      classical pathway activation, complexes are formed between C1q and activated C4
      or C3. Using ELISA, we investigated whether such complexes constitute specific
      markers for classical pathway activation. In vitro, C1q-C3d/C4d complexes were
      generated upon incubation of normal recalcified plasma with aggregated IgG or an
      anti-C1q mAb that activates C1 (mAb anti-C1q-130). In contrast, during incubation
      with C1s or trypsin, C1q-C3d/C4d complexes were not generated, which excludes an
      innocent bystander effect. Additionally, C1q-C3d/C4d complexes were not generated
      during activation of the alternative or the lectin pathway. Repeated freezing and
      thawing did not influence levels of C1q-C3d/C4d complexes in recalcified plasma.
      To measure C1q-complement complexes in plasma samples, we separated unbound
      complement proteins from C1q-C3d/C4d complexes in the samples prior to testing
      with ELISA. In samples from patients undergoing cardiopulmonary bypass surgery or
      suffering from rheumatoid arthritis, we found higher levels of C1q-C4 complexes
      than in samples from healthy individuals. We conclude that complexes between C1q
      and C4 or C3 are specific markers of classical complement pathway activation.

PMID- 15847796
TI  - Development of an edema factor-mediated cAMP-induction bioassay for detecting
      antibody-mediated neutralization of anthrax protective antigen.
AB  - Intoxication of mammalian cells by Bacillus anthracis requires the coordinate
      activity of three distinct bacterial proteins: protective antigen (PA), edema
      factor (EF), and lethal factor (LF). Among these proteins, PA has become the
      major focus of work on monoclonal antibodies and vaccines designed to treat or
      prevent anthrax infection since neither EF nor LF is capable of inducing cellular
      toxicity in its absence. Here, we present the development of a sensitive,
      precise, and biologically relevant bioassay platform capable of quantifying
      antibody-mediated PA neutralization. This bioassay is based on the ability of PA
      to bind and shuttle EF, a bacterial adenylate cyclase, into mammalian cells
      leading to an increase in cAMP that can be quantified using a sensitive
      chemiluminescent ELISA. The results of this study indicate that the cAMP
      induction assay possesses the necessary performance characteristics for use as
      both a potency-indicating release assay in a quality control setting and as a
      surrogate pharmacodynamic marker for ensuring the continued bioactivity of
      therapeutic antibodies against PA during clinical trials.

PMID- 15847797
TI  - Efficient elutriation of monocytes within a closed system (Elutra) for clinical
      scale generation of dendritic cells.
AB  - Dendritic cells (DC) are promising tools for the immunotherapy of cancer. The
      induction of tumor-specific T cells and clinical regressions have already been
      observed in early phase I/II vaccination trials. As DC vaccination is now facing
      trials with larger patient collectives it becomes increasingly important to
      obtain large numbers of cells suitable for therapeutic applications under labor-
      and cost-effective conditions. We describe here a procedure that uses a novel
      cell separator (Elutra, Gambro BCT) to enrich monocytes from an entire apheresis
      product within one hour. Cells are separated on the basis of size and to a lesser
      extent density, by elutriation in a 40-ml conical chamber. The total monocyte
      recovery following elutriation (n = 6) was 98.53% (+/-8.07%), the recovery in the
      monocyte-rich fraction 75.45% (+/-11.31%), and the mean purity 82.95% (+/-6.01%).
      These monocytes can be cultured either in conventional culture dishes or in
      closed cell culture bags and differentiated, by using GM-CSF+IL-4 followed by a
      maturation cocktail composed of IL-1beta+IL-6+TNF-alpha+PGE2, into fully mature
      DC. The Elutra separator allows for fast and easy enrichment of monocytes within
      a closed system. Subsequently, elutriated monocytes can be successfully cultured
      into phenotypically and functionally mature DC for immunotherapeutic approaches.
      The method neither requires a density gradient step to enrich PBMC from
      leucapheresis products nor does it apply (xenogeneic) antibodies to target
      monocytes. Isolation of monocytes with Elutra may greatly facilitate future DC
      based vaccination approaches.

PMID- 15847798
TI  - Lipopolysaccharide microarrays for the detection of antibodies.
AB  - Lipopolysaccharide (LPS) is the major component of Gram-negative bacterial outer
      membrane. LPS are immunogenic and show species/strain specificity. The
      demonstration of anti-LPS antibodies in clinical samples is of diagnostic value
      in certain Gram-negative bacterial infections. In the present study we explored
      the possibility of immobilizing LPS isolated from different bacteria in a
      microarray format for the detection of anti-LPS antibodies. LPS was successfully
      immobilized on nitrocellulose-coated glass slides, preserving the accessibility
      of epitopes for antibody binding. Specificity of the LPS arrays was established
      using four different monoclonal antibodies specific for Escherichia coli O111, E.
      coli O157, Francisella tularensis and Salmonella typhimurium O-antigens and a
      panel of LPS preparations. The detection limit of antibodies was found to be 10
      ng/ml, which is about a 100-fold greater sensitivity compared to conventional
      immunofluorescence assays. Furthermore, using LPS arrays, tularemia positive
      canine serum samples could be differentiated from negative samples based on the
      presence of significantly higher levels of anti-F. tularensis LPS antibodies in
      positive samples. LPS arrays will facilitate simultaneous screening of samples
      against multiple antigens and are expected to find applications in diagnostics
      and seroepidemiology.

PMID- 15847799
TI  - An efficient method for cloning human autoantigen-specific T cells.
AB  - T-cell clones are valuable tools for investigating T-cell specificity in
      infectious, autoimmune and malignant diseases. T cells specific for clinically
      relevant autoantigens are difficult to clone using traditional methods. Here we
      describe an efficient method for cloning human autoantigen-specific CD4+ T cells
      pre-labelled with CFSE. Proliferating, antigen-responsive CD4+ cells were
      identified flow cytometrically by their reduction in CFSE staining and single
      cells were sorted into separate wells. The conditions (cytokines, mitogens and
      tissue culture plates) for raising T-cell clones were optimised. Media
      supplemented with IL-2+IL-4 supported growth of the largest number of antigen
      specific clones. Three mitogens, PHA, anti-CD3 and anti-CD3+anti-CD28, each
      stimulated the growth of similar numbers of antigen-specific clones. Cloning
      efficiency was similar in flat- and round-bottom plates. Based on these findings,
      IL-2+IL-4, anti-CD3 and round-bottom plates were used to clone FACS-sorted
      autoantigen-specific CFSE-labelled CD4+ T cells. Sixty proinsulin- and 47
      glutamic acid decarboxylase-specific clones were obtained from six and two
      donors, respectively. In conclusion, the CFSE-based method is ideal for cloning
      rare, autoantigen-specific, human CD4+ T cells.

PMID- 15847800
TI  - Prolonged and increased expression of soluble Fc receptors, IgG and a TCR-Ig
      fusion protein by transiently transfected adherent 293E cells.
AB  - In studies of the relation between structure and function of proteins of the
      immune system, there is a continuous need for screening of a large number of
      protein variants. To optimise the yield following transient gene expression in
      small or medium culture volumes, several parameters were investigated. First,
      secretion levels of a soluble form of human Fcgamma receptor IIA (FcgammaRIIA)
      were measured after transfection of 293, 293E, 293T as well as COS-7 cell lines.
      The transgene was under cytomegalovirus (CMV) promoter control on the expression
      vector pcDNA3, which also contains an SV40 origin of replication (SV40 ori). All
      293 cell lines secreted more protein than COS-7 cells. Introduction of the
      Epstein Barr virus (EBV) origin of replication (oriP) greatly increased the
      protein expression from the 293E cells, both the amount of protein produced per
      day and the duration of production. At best, 293E cells secreted fully functional
      protein for 3-4 weeks provided supernatant was harvested every 2-3 days followed
      by medium replacement. This method was then used for expression of soluble forms
      of human FcgammaRI, FcgammaRIIB, the human neonatal Fc receptor (FcRn), a T cell
      receptor (TCR)-immunoglobulin (Ig) fusion protein, and human IgG3. With an
      initial culture volume of 5 ml, the yield was approximately 200 microg for
      FcgammaRIIA, 1.5 microg for FcgammaRI, 5 microg for FcRn, 20 microg for
      FcgammaRIIB, 40 microg for the TCR-Ig fusion protein and 850 microg for IgG3.
      Culture expansion during the 3 weeks of culture further increased the yield.
      Protein yield was also improved by scaling up the initial volume. This approach
      can provide sufficient amounts of protein for screening experiments, and in the
      case of antibody, milligrams of recombinant protein for extensive structural
      analysis can be obtained from one single transient transfection. The approach
      should be of interest to laboratories that do not have access to a bioreactor but
      still have a requirement for reasonable amounts of protein to be produced in an
      easy and cost-effective manner.

PMID- 15847801
TI  - A vaccinia-based elispot assay for detection of CD8+ T cells from HIV-1 infected
      children.
AB  - HIV-specific CD8+ T lymphocytes participate in the control of viral replication
      in infected patients. These responses are of low intensity in young infants and
      are decreased by antiretroviral therapy. In the present study, we report on a
      recombinant Vaccinia virus (rVV)-based Elispot assay for the detection of HIV
      specific CD8+ T cells immediately after isolation of peripheral blood mononuclear
      cells (PBMC). The rVV-based assay was highly sensitive; 48 out of 50 children had
      a positive response against the rVV encoding HIV Env-Gag-Pol antigen. Interferon
      gamma was produced by CD8+ T cells, and CD14+/15+ cells were the main cell subset
      presenting antigens expressed by rVV. We observed that the cell input per well
      had a critical influence on the sensitivity of the assay. Results from the ex
      vivo Elispot assay correlated poorly with those of the 51Cr release assay
      performed after expansion of PBMC in vitro; thus, both assays gave information on
      different subsets and/or functions of the HIV-specific T cell response.

PMID- 15847802
TI  - Use of a new immunoassay to measure PrP Sc levels in scrapie-infected sheep
      brains reveals PrP genotype-specific differences.
AB  - The diagnosis of prion diseases, such as scrapie and BSE, has traditionally
      relied upon the identification of the disease-associated form of the prion
      protein, PrP(Sc), based on its resistance to digestion by proteinase K (PK). A
      more recent development is the conformation-dependent immunoassay (CDI), which
      distinguishes between PrP Sc and normal PrP (PrP C) based on their differing
      solubility in guanidine hydrochloride rather than resistance or sensitivity to
      PK. We have developed a CDI-formatted sandwich immunoassay for the measurement of
      PrP Sc in sheep brain, which discriminates between clinically affected scrapie
      cases (natural or experimental) and uninfected controls of the same PrP genotype.
      Using this method, we have shown for the first time that, in sheep, the PrP
      genotype has a significant influence on the amount of PrP Sc deposited in the
      brains of animals experimentally infected with scrapie.

PMID- 15847803
TI  - Effect of sample handling on analysis of cytokine responses to Mycobacterium
      tuberculosis in clinical samples using ELISA, ELISPOT and quantitative PCR.
AB  - Measuring cytokine responses to infection has proven to be invaluable for the
      understanding of immunity to tuberculosis in the laboratory. However, far less
      data are available from studies in humans and these have often produced
      conflicting results. Here we describe a comprehensive multi-center comparison of
      the most commonly used protocols for cytokine analysis: ELISA, ELISPOT and RT
      PCR, in cohorts of TB patients, their household contacts and community controls.
      In particular, we have studied the effect on these protocols of conditions that
      commonly prevail in field studies, such as delays between sample collection and
      analysis, or different source material, such as whole blood or frozen PBMC. The
      results clearly show that while there is good correlation between the methods
      under optimal conditions, each method has strengths and weaknesses that render
      them more or less suitable for particular types of analyses. Researchers should
      carefully consider these factors when planning human field studies.

PMID- 15847804
TI  - A new method to measure air-borne pyrogens based on human whole blood cytokine
      response.
AB  - Air-borne microorganisms, as well as their fragments and components, are
      increasingly recognized to be associated with pulmonary diseases, e.g. organic
      dust toxic syndrome, humidifier lung, building-related illness, "Monday
      sickness." We have previously described and validated a new method for the
      detection of pyrogenic (fever-inducing) microbial contaminations in injectable
      drugs, based on the inflammatory reaction of human blood to pyrogens. We have now
      adapted this test to evaluate the total inflammatory capacity of air samples. Air
      was drawn onto PTFE membrane filters, which were incubated with human whole blood
      from healthy volunteers inside the collection device. Cytokine release was
      measured by ELISA. The test detects endotoxins and non-endotoxins, such as fungal
      spores, Gram-positive bacteria and their lipoteichoic acid moiety and pyrogenic
      dust particles with high sensitivity, thus reflecting the total inflammatory
      capacity of a sample. When air from different surroundings such as working
      environments and animal housing was assayed, the method yielded reproducible data
      which correlated with other parameters of microbial burden tested. We further
      developed a standard material for quantification and showed that this assay can
      be performed with cryopreserved as well as fresh blood. The method offers a test
      to measure the integral inflammatory capacity of air-borne microbial
      contaminations relevant to humans. It could thus be employed to assess air
      quality in different living and work environments.

PMID- 15847805
TI  - Effect of fixation protocols on in situ detection of L-selectin ligands.
AB  - In situ binding of (chimeric) proteins to tissue sections is a widely used method
      to identify ligands and their localization. Many different protocols for the
      fixation of frozen tissue sections are used for in situ binding studies. We
      report the effects of different fixation protocols on the binding pattern
      observed using in situ binding of an L-selectin-IgM chimeric protein to both rat
      lymph node and kidney tissue sections. L-selectin is a C-type lectin, expressed
      on leukocytes and is involved in both lymphocyte homing and migration upon
      inflammation. We show that different in situ binding patterns in rat kidney are
      observed using different fixation protocols, including glutaraldehyde, methanol,
      formaldehyde and acetone fixation. The observed staining is specific, as it can
      be blocked in the presence of EGTA, an L-selectin blocking antibody or by ligand
      competition. Enzymatic pre-treatment of the tissue sections using sialidase,
      heparitinase I or chondroitinase ABC has differential effects on in situ binding
      depending on tissue type and fixation protocol. These data indicate that special
      attention should be paid in choosing a fixation protocol for in situ binding
      studies, especially when using lectins. This could prevent biologically relevant
      ligands remaining undetected or wrong conclusions being drawn based on the
      localization of observed binding.

PMID- 15847806
TI  - International validation of novel pyrogen tests based on human monocytoid cells.
AB  - It is a requirement that parenteral medicines be tested for pyrogens (fever
      causing agents) using one of two animal-based tests: the rabbit pyrogen test and
      the bacterial endotoxin test. Understanding the human fever reaction has led to
      novel non-animal alternative tests based on in vitro activation of human
      monocytoid cells in response to pyrogens. Using 13 prototypic drugs, clean or
      contaminated with pyrogens, we have validated blindly six novel pyrogen tests in
      ten laboratories. Compared with the rabbit test, the new tests have a lower limit
      of detection and are more accurate as well as cost and time efficient. In
      contrast to the bacterial endotoxin test, all tests are able to detect Gram
      positive pyrogens. The validation process showed that at least four of the tests
      meet quality criteria for pyrogen detection. These validated in vitro pyrogen
      tests overcome several shortcomings of animal-based pyrogen tests. Our data
      suggest that animal testing could be completely replaced by these evidence-based
      pyrogen tests and highlight their potential to further improve drug safety.

PMID- 15847807
TI  - Functional canine dendritic cells can be generated in vitro from peripheral blood
      mononuclear cells and contain a cytoplasmic ultrastructural marker.
AB  - For physiological and practical reasons the dog is a large animal model used
      increasingly to study the pathogenesis of human diseases and new therapeutic
      approaches, in particular for immune disorders. However, some immunological
      resources are lacking in this model, especially concerning dendritic cells. The
      aim of our study was to develop an efficient method to generate dendritic cells
      (DC) in vitro from dog peripheral blood mononuclear cells (PBMC) and to
      characterize their functional, structural and ultrastructural properties. PBMC
      were cultured in vitro with IL-4 and GM-CSF. After 1 week of culture, a great
      proportion of non-adherent cells displayed typical cytoplasmic processes, as
      evidenced both by optical and electron microscopy. Cytometric analysis revealed
      the presence of 41.7+/-24.6% CD14+ cells expressing both CD11c and MHC class II
      molecules. Allogeneic mixed lymphocyte reactions confirmed the ability of these
      cultures to stimulate the proliferation of allogeneic lymphocytes as already
      reported as a characteristic of DC in other species. In addition, we describe for
      the first time the presence in canine DC of cytoplasmic periodic microstructures
      (PMS) that could represent ultrastructural markers of canine DC. In conclusion,
      our study provides an easy method to generate DC from PBMC in sufficient numbers
      for immunological in vitro investigations in dogs, a pre-clinical model for many
      human diseases.

PMID- 15847808
TI  - Quantifying cell turnover using CFSE data.
AB  - The CFSE dye dilution assay is widely used to determine the number of divisions a
      given CFSE labelled cell has undergone in vitro and in vivo. In this paper, we
      consider how the data obtained with the use of CFSE (CFSE data) can be used to
      estimate the parameters determining cell division and death. For a homogeneous
      cell population (i.e., a population with the parameters for cell division and
      death being independent of time and the number of divisions cells have
      undergone), we consider a specific biologically based "Smith-Martin" model of
      cell turnover and analyze three different techniques for estimation of its
      parameters: direct fitting, indirect fitting and rescaling method. We find that
      using only CFSE data, the duration of the division phase (i.e., approximately the
      S+G2+M phase of the cell cycle) can be estimated with the use of either
      technique. In some cases, the average division or cell cycle time can be
      estimated using the direct fitting of the model solution to the data or by using
      the Gett-Hodgkin method [Gett A. and Hodgkin, P. 2000. A cellular calculus for
      signal integration by T cells. Nat. Immunol. 1:239-244]. Estimation of the death
      rates during commitment to division (i.e., approximately the G1 phase of the cell
      cycle) and during the division phase may not be feasible with the use of only
      CFSE data. We propose that measuring an additional parameter, the fraction of
      cells in division, may allow estimation of all model parameters including the
      death rates during different stages of the cell cycle.

PMID- 15847810
TI  - Radiologic evaluation of the solitary pulmonary nodule.
AB  - The solitary pulmonary nodule (SPN) is a common radiologic finding. There are
      different management approaches and the work-up often requires evaluation over a
      long period of time to establish a benign or malignant diagnosis. Comparison with
      old examinations and morphologic evaluation of the size, margins, and internal
      characteristics of an (SPN) should be the first step in the evaluation of these
      lesions. It is often necessary to proceed to additional imaging techniques and in
      some situations invasive tests or surgical biopsy may be required.

PMID- 15847811
TI  - Imaging of non-small cell lung cancer.
AB  - Radiologic evaluation is an important component of the clinical staging
      evaluation of lung cancer and can greatly influence whether the patient is
      treated with surgical resection, radiation therapy, chemotherapy, or a
      combination of these modalities. In addition to staging, the radiologic
      evaluation of the patient undergoing treatment and subsequent follow-up is
      important to the clinician for assessing treatment effects and complications.
      This article discusses the imaging of patients with non-small cell lung cancer
      and its use in management of these patients.

PMID- 15847812
TI  - Imaging of metastatic disease to the thorax.
AB  - Tumor imaging is at the forefront of radiology technology and is the focus of
      most cutting edge research. Radiologic applications for imaging of metastases are
      applied to initial staging, restaging after neoadjuvant therapy, and follow-up
      surveillance after therapy for tumor recurrence. CT is the routine imaging choice
      in staging, restaging, and detection of recurrence. Fluorodeoxyglucose-positron
      emission tomography has evolved as an imaging modality that further improves
      staging as well as the detection of recurrent and metastatic disease.

PMID- 15847813
TI  - Radiology of community-acquired pneumonia.
AB  - This article reviews the radiographic appearance of common community-acquired
      pneumonia. Included are the common bacterial pneumonias, tuberculosis, fungal
      pneumonia, pneumocystis pneumonia, and viral pneumonias. The various radiographic
      appearances and the clues for differentiating the pneumonias are discussed.
      Images enhance the discussion.

PMID- 15847814
TI  - High-resolution CT of the lung: patterns of disease and differential diagnoses.
AB  - High-resolution CT (HRCT) of the lung is a powerful tool for the investigation of
      patients with acute or chronic respiratory symptoms or diffuse parenchymal lung
      disease. Detailed knowledge of normal pulmonary anatomy and an understanding of
      how normal anatomy is altered in disease states are required to appreciate fully
      HRCT findings in patients with pulmonary disease. Detailed knowledge of the
      technical aspects of HRCT examinations is required for optimal image quality.
      With the proper foundation, a pattern approach to HRCT interpretation may then be
      used successfully to provide accurate and reproducible interpretation.

PMID- 15847815
TI  - Vascular diseases of the thorax: evaluation with multidetector CT.
AB  - The list of vascular diseases in the thorax has been narrowed to three, which are
      considered essential information for radiologists interpreting CT scans of the
      thorax: (1) aortic dissection and its variants, intramural hematoma and
      penetrating atherosclerotic ulcer; (2) acute pulmonary embolism; and (3) coronary
      artery disease. The spatial resolution of multidetector CT is such that CT has
      become the imaging modality of choice for aortic dissection and pulmonary
      embolism. This move away from angiography has transpired over the last decade;
      perhaps the next decade will see the same occur for evaluation of coronary artery
      disease.

PMID- 15847820
TI  - Possible factors contributing to the postmortem lung weight in fire fatalities.
AB  - The aim of the present study was to examine the factors that contribute to the
      postmortem lung weight in acute fire fatalities (n=149) including those with
      lower (<60%) and higher (>60%) blood carboxyhemoglobin (COHb) levels (n=94 and
      55, respectively). The control groups consisted of acute myocardial
      infarction/ischemia (AMI, n=99) and mechanical asphyxiation (n=85). For all cases
      (n=333), the lung and heart weights were independent of the postmortem time (4.5
      72 h) and charring of the body. The combined weight of both lobes of the lung
      showed a significant gender difference (males>females, P<0.001), negative
      regression with respect to age (R=0.167, P<0.01) and positive regression with
      respect to heart weight (R=0.316, P<0.001). The gender difference was also
      significant for each cause of death even after being corrected using body height
      measurements. When the lung-heart weight ratio was estimated to diminish the
      influence of possible cardiogenic factors, the gender difference was
      insignificant for each cause of death among the non-elderly (<60 years of age).
      However, for elderly fire fatalities (>60 years of age), there was a gender
      difference (males>females) for the lower COHb group (P<0.05) and higher COHb
      group (P<0.001). A significant age-dependent difference (non-elderly>elderly) in
      the lung-heart weight ratio was observed for fire fatalities with a lower COHb
      and AMI among males and for fire fatalities with a higher COHb among females.
      Such gender- and/or age-dependent influences were not significant for fatal
      mechanical asphyxiation. These findings suggest that a person's heart weight may
      be a possible contributory factor to an increase in the lung weight in acute
      death, and that gender- and/or age-dependent susceptibilities may be additional
      factors that contribute to fire fatalities and AMI. In addition, elderly females
      appear to be most susceptible among fire casualties, and extreme cardiomegaly may
      also be a potential fatal risk factor.

PMID- 15847821
TI  - Ubiquitin-immunoreactive structures in the midbrain of methamphetamine abusers.
AB  - Ubiquitin (Ub) is involved in neurodegeneration and various stress responses in
      the brain. The present study investigated the Ub-immunoreactive structures in the
      midbrain of methamphetamine (MA) abusers as a marker of drug-induced
      neurodegeneration. Medico-legal autopsy cases were examined: fatal MA
      intoxication (n=14), other fatalities of MA abusers (n=23) including those due to
      injuries, asphyxiation, drowning, fire and natural diseases, and control groups
      (n=260). In the motor nervous systems, MA abusers showed a mild increase in the
      diffuse-type nuclear Ub-positivity in the pigmented neurons of the substantia
      nigra, depending on the blood MA level and irrespectively of the immediate causes
      of death. The intranuclear inclusion-type Ub-positivity of the nigral neurons and
      the granular 'dot-like' Ub-immunoreactivity area in the crus cerebri (cortico
      spinal tracts) were usually low in MA abusers, and any increases were related to
      the immediate causes of death and the age of subjects. Acute MA fatality showed a
      higher neuronal Ub-positivity in the midbrain periaqueductal gray matter (PGM),
      which is involved in processing pain, fear and anxiety, and regulation of
      respiration and circulation. These findings suggest dysfunction of the nigral
      dopaminergic neurons and PGM neurons in the midbrain in MA abuse, which may
      account for the clinical symptoms.

PMID- 15847822
TI  - Quantitative analysis of ubiquitin-immunoreactivity in the midbrain
      periaqueductal gray matter with regard to the causes of death in forensic
      autopsy.
AB  - The aim of the present study was to examine Ub-immunoreactivity in the midbrain
      periaqueductal gray matter (PGM), which is involved in pain processing and
      modulation, in forensic autopsy cases (n=273) in relation to the causes of death:
      acute deaths from blunt injuries (n=75), sharp weapon injuries (n=36), fatal
      asphyxiation (n=22), drownings (n=16: freshwater, n=9; saltwater, n=7), fire
      fatalities (n=64), poisoning (n=12), hyperthermia (n=5), hypothermia (n=5),
      delayed deaths from blunt head injury (n=8), acute cardiac deaths (n=24), and
      acute cerebrovascular strokes (n=6). The Ub-immunoreactivity was clearly observed
      in the nuclei of the PGM neurons, showing no postmortem interference or age
      dependency. A higher value was observed in blunt injuries, fire fatalities and
      also in saltwater drowning, hyperthermia and delayed head injury deaths. These
      findings suggest a complicated mechanism for the ubiquitination of PGM neurons,
      to which multiple factors including the intensity and duration of pains possibly
      under alert consciousness, traumatic and metabolic neurodegeneration may
      contribute.

PMID- 15847823
TI  - Ubiquitin immunoreactivity in the midbrain as a marker of stress to motor nervous
      systems in fatal injury.
AB  - Previous studies showed an increase in the ubiquitin (Ub)-immunoreactive
      structures in the midbrain in acute deaths from asphyxiation and in fires in
      adult subjects. The present study examined the Ub-immunoreactivity in the
      midbrain as a marker of stress to motor nervous systems in fatal injury cases
      (over 35 years of age, n=140: blunt injuries, n=82; sharp injuries, n=58),
      compared with that in control groups (n=61) including death by strangulation,
      acute cardiac and cerebrovascular diseases. The intranuclear Ub-immunopositive
      inclusion of the pigmented dopaminergic neurons of the substantia nigra
      (inclusion Ub-index) and the granular 'dot-like' Ub-immunoreactivity area ('dot
      like' Ub-area) in the crus cerebri were analyzed. In blunt injuries, those
      markers were high in abdomen and back injuries and low in head and chest
      injuries. The inclusion Ub-index was higher in the crush/pressure injury group
      than in those with injuries due to impact traffic accidents and falls. 'Dot-like'
      Ub-area was also low in falls. In sharp injury cases, cardiac injury with
      hemopericardium showed a higher inclusion Ub-index. These findings suggested that
      the stress to the motor nervous system may be very intense in crush/pressure
      injury and hemopericardium than in impact injury and fatal hemorrhages,
      respectively, and in abdomen and back injuries than in head and chest injuries.

PMID- 15847824
TI  - Application of the BioRobot EZ1 in a forensic laboratory.
AB  - In a forensic laboratory, the routine application of an automated DNA extraction
      and purification robot has to fulfil several conditions, like producing
      reproducible DNA's of sufficient quantity and quality from all the different
      forensic biological stains relevant to various carrier materials. In this study,
      the suitability of the BioRobot EZ1 system from QIAGEN (Hilden, Germany), which
      offers fully automated extraction and purification of nucleic acids using
      magnetic bead technology, was tested. In summary, the DNA's obtained from the
      BioRobot EZ1 for different forensic relevant biological materials showed a
      quantity and quality comparable to those of the forensic standard protocols
      normally used in our laboratory. The system saves time, because there is no need
      of any further purification or concentration step after the automated DNA
      extraction. It can also be used as a replacement for time consuming organic
      extractions. A disadvantage of the system was the unsteady quality of the
      chemical regencies used by the robot. Nineteen different lots were tested with a
      self designed test system.

PMID- 15847825
TI  - The relationship of a high level of serum beta-hydroxybutyrate to cause of death.
AB  - To examine the state of ketoacidosis in relation to the cause of death, three
      kinds of ketone bodies (acetoacetate, beta-hydroxybutyrate and acetone) were
      measured in postmortem serum. Of 100 autopsy cases, 22 had ketone body increasing
      pathophysiological conditions, overlapped in some cases, namely a poorly
      nourished state (10 cases), alcoholic fatty liver damage (10), diabetes (5) and
      infectious disease (5). Of the 3, 11, 7 and 15 cases in which the beta
      hydroxybutyrate concentration was greater than 10,000, 1000-10,000, 500-1000 and
      200-500 micromol/l, 3 (100%), 8 (73%), 3 (43%) and 5 (33%), respectively, had one
      or more pathophysiological conditions that usually produce ketone bodies. Of the
      64 cases in which the beta-hydroxybutyrate concentrations were less than 200
      micromol/l, only 3 (5%) had some of these conditions. Cases showing high levels
      of ketone bodies tended to have pathophysiological states that can produce them,
      although the level of beta-hydroxybutyrate and these states did not show parallel
      relationships. When autopsy findings fail to explain the cause of death, a
      diagnosis as death caused by ketoacidosis would be reasonable if the serum beta
      hydroxybutyrate level is over 1000 micromol/l and the body has pathophysiological
      conditions that tend to increase ketone bodies.

PMID- 15847826
TI  - Species identification of the forensically important flies in Iwate prefecture,
      Japan based on mitochondrial cytochrome oxidase gene subunit I (COI) sequences.
AB  - Molecular biological species identification of forensically important flies
      distributed in Iwate prefecture, Japan, was carried out, and the utility of this
      method was evaluated. The dipteran nymphs that were early colonizers on the
      corpse were reared to adult and morphologically identified. Meanwhile they were
      sequenced over a 304 base pair region of the mitochondrial cytochrome oxidase
      gene subunit I (COI). Six species belonging three genera of Calliphoridae
      (Calliphora lata, C. vicina, Lucilia cuprina, L. illustris, L. sericata,
      Chrysomya pinguis) and two species of Sarcophagidae (Parasarcophaga crassipalpis,
      P. similis) were collected and identified. Each fly had somewhat different
      ecological features such as seasonal dominance and habitat. The COI sequences of
      each species were unique and distinguishable from each other, although they
      showed high homology. Species identification from immature diptera by the DNA
      sequences was simple and time-saving because there was no need to wait for adult
      emergence or knowledge of morphological keys, and it provided information about
      not only postmortem interval but also seasonal and environmental conditions
      surrounding the corpse.

PMID- 15847827
TI  - Applicability of the parentally imprinted allele (PIA) typing of a VNTR upstream
      the H19 gene to forensic samples of different tissues.
AB  - The parentally imprinted allele (PIA) typing that we have recently developed
      determines parental alleles at a VNTR locus in the differentially methylated
      region upstream of the human H19 gene. The usefulness of this typing was
      demonstrated by its application to blood samples in paternity cases. However, its
      applicability to other tissue DNA remains to be tested. DNA samples from fifteen
      different postmortem tissues such as cerebrum, skeletal muscle and skin were
      examined, all of which were obtained from three autopsy cases 2-11h after death.
      DNA was digested with a methylation-sensitive HhaI enzyme and diluted solutions
      of the digests were subjected to the first PCR amplification, providing
      amplification of only the paternal H19 methylated allele. Subsequent VNTR typing
      was carried out for the amplified products to determine which allele was of
      paternal origin. No tissue-dependent difference was observed and all the samples
      examined, though degraded, were successfully used for determining the paternal
      allele. These results substantiate the usefulness of PIA typing in forensic
      examinations. Its application to two identity cases, a burned male body and a
      male body with adipocere formation, was also shown.

PMID- 15847828
TI  - Improvement of a multiplex PCR system for DYS441, DYS442, DYS443, DYS444 and
      DYS445, and a population study in 340 Japanese males.
AB  - A multiplex PCR system for five Y-STRs (DYS441, DYS442, DYS443, DYS444 and
      DYS445) has been improved to increase the probability of obtaining a DNA typing
      result from aged samples. Newly designed PCR primers for amplification of the
      DYS441 and DYS442 loci and optimization of PCR conditions enabled successful
      typing from blood and semen stains that had been stored for more than seven years
      at room temperature. Analysis of 340 Japanese males revealed 7, 5, 6, 5 and 4
      alleles at the DYS441, DYS442, DYS443, DYS444 and DYS445 loci, respectively,
      yielding 122 haplotypes with a cumulative haplotype diversity of 0.97.

PMID- 15847829
TI  - Gender-specific amplification of Japanese macaque genes using primers for the
      human DYS391 and DYS438 loci.
AB  - The species specificity of 10 human Y chromosomal short tandem repeat loci,
      DYS19, DYS385, DYS389, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439,
      was examined in the Japanese macaque, Macaca fuscata. Primers for loci DYS391 and
      DYS438 only yielded an amplification product from male samples. The PCR products
      amplified with the DYS391 primers showed no inter-individual differences in
      migration rate in electrophoretic experiments. Sequence analysis revealed that
      these PCR products consisted of 287 bases containing tandem repeats of TC and
      TATC. The numbers of TC and the TATC repeats varied between individuals. The TC
      repeat does not exist in human and chimpanzee sequences. The PCR products
      amplified by the DYS438 primers provided no evidence of inter-individual
      variation between the six male Japanese macaque samples. In the Japanese macaque,
      PCR gives a 184 base pair product, in contrast to human sample from which the
      products are 203-233 bases in size. The primers for four loci, DYS19, DYS385,
      DYS389 and DYS437 produced PCR products from both male and female Japanese
      macaques. The primers for the other loci, DYS390, DYS392, DYS393 and DYS439, did
      not yield PCR products.

PMID- 15847830
TI  - Demonstration of A antigen and A allele of ABO histo-blood group in nail in a
      case with the absence of A antigen and anti-A antibody in blood.
AB  - We report a case with the inconsistency that the red blood cells lacked both A-
      and B-antigens while the serum showed reactivity with control B-red cells but not
      with A-red cells. A- and B-antigens were examined by serological blood typing and
      immunohistochemical staining, and DNA analyses were performed using polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP), DNA
      sequencing, and hot-stop PCR. A-antigens were demonstrable in the nail of the
      subject by serological study and immunostaining. DNA analyses showed that the
      nail retained a small amount of A-allele comparing to that of O-allele. Those
      genomic analyses of ABO genes were useful for demonstration of A allele in the
      nail of an individual with the absence of A antigen on red blood cells and the
      corresponding antibody in serum.

PMID- 15847831
TI  - Simple colorimetric semiquantitation method of hippuric acid in urine for
      demonstration of toluene abuse.
AB  - A semiquantitative method for hippuric acid in toluene sniffers' urine was
      explored by modifying the method by Tomokuni and Ogata. The color of sample urine
      mixed with pyridine and benzenesulfonyl chloride was yellow, and became reddish
      by addition of distilled water. Using the color chart, the concentration of
      hippuric acid could be semiquantitated in a few minutes. The values determined by
      this method were compared with those obtained by high performance liquid
      chromatography, showing a coefficient of determination (r2) of 0.8594. This
      colorimetric method is thus useful for rapid screening for hippuric acid in
      urine, or toluene sniffing.

PMID- 15847832
TI  - Genetic data on 13 STR loci in the Andalusian (South Spain) population.
AB  - The aim of this paper was to obtain allelic frequencies for the 13 CODIS core STR
      loci (D3S1358, VWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D16S539, TH01,
      TPOX, CSF1PO, and D7S820) from autochthonous individuals from Andalusia, Spain.
      In addition, a number of forensically useful genetic parameters are reported.

PMID- 15847833
TI  - Prednisone for Duchenne muscular dystrophy.

PMID- 15847834
TI  - Cardiac pacing: atrial fibrillation may go unrecognised.

PMID- 15847835
TI  - Antioxidant treatment for amyotrophic lateral sclerosis.

PMID- 15847836
TI  - Results from the FOOD trial.

PMID- 15847837
TI  - Infectious causes of multiple sclerosis.

PMID- 15847838
TI  - Infectious causes of multiple sclerosis.

PMID- 15847840
TI  - Treatment of pseudobulbar affect in ALS.

PMID- 15847841
TI  - Clinically isolated syndromes suggestive of multiple sclerosis, part I: natural
      history, pathogenesis, diagnosis, and prognosis.
AB  - In 85% of young adults with multiple sclerosis (MS), onset is a subacute
      clinically isolated syndrome (CIS) of the optic nerves, brainstem, or spinal
      cord. Methods of assessing the prognosis for patients who present with a CIS have
      been sought, because only 30-70% of patients with a CIS develop MS. When
      clinically silent brain lesions are seen on MRI, the likelihood of developing MS
      is high. MS can be diagnosed within 3 months of CIS presentation with certain MRI
      and CSF criteria. Disability from MS is less likely in patients with a CIS of
      optic neuritis or sensory symptoms only, few or no MRI lesions, a long period to
      the first relapse, and no disability after the first 5 years. Development of more
      reliable prognostic markers will enable new treatments to be targeted for those
      who are most likely to benefit. We encourage continued clinical and laboratory
      assessment of patients with a CIS.

PMID- 15847842
TI  - Therapeutic management of brain metastasis.
AB  - This review focuses on the management of brain metastases. The four main modes of
      therapy are discussed: whole brain radiation therapy (WBRT), surgery,
      radiosurgery, and chemotherapy. Young patients with limited extracranial disease
      may benefit from surgical resection of a single brain metastasis, and from
      radiosurgery (or stereotactic radiotherapy) if two to four brain metastases are
      present. Whether WBRT after surgery or radiosurgery is beneficial is uncertain.
      Therefore, two approaches can be justified in patients with a good prognosis:
      WBRT after surgery or radiosurgery, or alternatively, observation with MRI follow
      up after surgery or radiosurgery. A hyperfractionated radiation scheme is then to
      be preferred to limit late toxicity of WBRT. Patients with extensive extracranial
      tumour activity or impaired quality of life may benefit from radiosurgery (one to
      four brain metastases), or from shorter WBRT schedules. We propose a decision
      tree on the various ways to treat brain metastasis.

PMID- 15847843
TI  - Brain arteriovenous malformations in adults.
AB  - Arteriovenous malformations of the brain (AMB) can cause stroke when they
      rupture. Epidemiological and imaging research has found that about 50% of
      patients with AMB present with haemorrhage, and the other 50% either present with
      non-focal symptoms, such as headache, seizure, or focal neurological deficit, or
      have no symptoms and the lesion is found during unrelated investigations.
      Treatment for arteriovenous malformations aims to prevent and resolve haemorrhage
      and is a growing interdisciplinary challenge. Although treatment uses enormous
      resources, there have been few studies on the risk-benefit ratios for treatment
      of unruptured AMB and the best approaches.

PMID- 15847844
TI  - Multifocal motor neuropathy.
AB  - Multifocal motor neuropathy (MMN) is an immune-mediated disorder characterised by
      slowly progressive, asymmetrical weakness of limbs without sensory loss. The
      clinical presentation of MMN mimics that of lower-motor-neuron disease, but in
      nerve-conduction studies of patients with MMN motor-conduction block has been
      found. By contrast with chronic inflammatory demyelinating polyneuropathy,
      treatment with prednisolone and plasma exchange is generally ineffective in MMN
      and even associated with clinical worsening in some patients. Of the
      immunosuppressants, cyclophosphamide has been reported as effective but only
      anecdotally. Various open trials and four placebo-controlled trials have shown
      that treatment with high-dose intravenous immunoglobulin leads to improvement of
      muscle strength in patients with MMN. Although clinical, pathological, imaging,
      immunological, and electrophysiological studies have improved our understanding
      of MMN over the past 15 years, further research is needed to elucidate
      pathogenetic disease mechanisms in the disorder.

PMID- 15847845
TI  - Anthropological contributions to the understanding of age-related cognitive
      impairment.
AB  - Medical anthropology has not only helped us to understand the social, political,
      and ethical foundations of modern biomedicine, but also improved the
      identification and treatment of patients in various geographic, sociological, and
      medical contexts. In this article, we present an anthropological perspective on
      the understanding, diagnosis, and treatment of age-related cognitive impairment.
      The ubiquity of cognitive changes in the growing number of elderly people around
      the world, and the many diverse responses that human communities have taken to
      such challenges, require biocultural approaches. Anthropology can serve as an
      ally in accomplishing the goal of improving the quality of life of those with
      cognitive impairment by highlighting the role of sociocultural processes that
      influence the development, meaning, and experience of dementia. So too can it
      serve as a framework for criticism of biomedical research, theory, and practice.

PMID- 15847846
TI  - Intensity of malaria transmission and the evolution of drug resistance.
AB  - The intensity of malaria transmission varies both naturally and as a consequence
      of human public health intervention. The relationship between transmission
      intensity and the rate at which antimalarial drug resistance evolves affects the
      design of surveillance programmes, and the likely impact of malaria control
      programmes. Several theoretical studies have investigated this relationship and
      their key results are summarised and interpreted. The most important result is
      that transmission intensity does not directly affect the evolution of resistance.
      It exerts its influence through three clinical/epidemiological "mediators"
      (clonal multiplicity, the threat of infection, level of human immunity) which
      ultimately determine the dynamics of resistance via five "effector" variables:
      sexual recombination, intrahost dynamics, community drug use, proportion of
      malaria infections treated, and the number of parasites per host. We argue that
      the evolution of resistance is likely to be a two-stage process: mutations
      encoding drug tolerance preceding those encoding resistance. The evolution of
      drug tolerance is determined solely by the level of drug use in the community
      which is likely to have an extremely weak relationship with transmission
      intensity. The evolution of resistance is more complex and affected by all five
      effectors. The most likely scenarios are that resistance evolves faster in areas
      of high transmission if encoded by a single gene but if encoded by two or more
      genes it evolves fastest in areas of high or low transmission, with a minimum at
      intermediate levels of transmission.

PMID- 15847847
TI  - beta-Minor globin gene expression is preferentially reduced in EKLF Knock-Out
      mice.
AB  - The CACCC box is duplicated in the beta-globin gene promoter of humans and other
      mammals. While the function of the proximal element as a binding site for EKLF
      has already been well established, the role of the distal element remains
      unclear. Mice present two adult beta-globin genes, beta-major and beta-minor,
      bearing a single CACCC box, the consensus sequence of which is identical to that
      of the proximal or distal human element, respectively. In the present study we
      analyzed the mRNA expression of beta-minor and beta-major in EKLF Knock-Out (KO)
      mice in comparison to wild-type (wt) littermates. The murine early fetal liver up
      to day 13/14 post coitum (pc) expresses mainly beta-minor globin chains.
      Nevertheless, expression of the beta-minor globin gene in EKLF KO mice has not
      been assessed to date. We provide evidence that expression of the beta-minor
      globin gene is dependent upon EKLF and is more affected by EKLF deprivation than
      the beta-major gene. The results obtained support a general role of EKLF in beta
      globin gene activation and are in agreement with models involving an advantage of
      the LCR proximal respect to distal gene.

PMID- 15847848
TI  - Zonisamide for absence seizures.
AB  - This chart review investigated the efficacy and safety of zonisamide in 45
      patients aged < or = 18 years with absence seizures. Of these patients, 23
      (51.1%) achieved freedom from absence seizures. Two patients discontinued
      zonisamide, 1 for increased seizures and 1 for sleepiness and inefficacy. These
      data support the efficacy of zonisamide in treating absence seizures.

PMID- 15847849
TI  - Neuropsychological correlates of electroencephalograms in children with epilepsy.
AB  - INTRODUCTION: This study examined the degree to which neurophysiological activity
      on routine clinical EEG is associated with neuropsychological deficiencies in
      children with epilepsy. METHODS: Ninety-five children with epilepsy (58 chronic,
      37 recent-onset; mean age = 10.41 years, S.D. = 2.87 years; mean age at onset =
      5.86 years, S.D. = 3.46 years) completed a neuropsychological battery.
      Neurophysiological data were collected from the most recent EEG. RESULTS: In the
      recent-onset sample, no neuropsychological scores were related to any EEG
      variable. In the chronic sample, however, presence of slow-wave activity was
      related to memory impairment (p < 0.01). Post-hoc analyses on other
      neuropsychological measures showed localization of epileptiform activity (EA)
      might be related to verbal learning. DISCUSSION: Children with slow-wave activity
      on EEG might be at increased risk for developing neuropsychological deficits.
      When these abnormalities are observed on a child's EEG, closer monitoring of
      cognitive and academic functioning seems warranted. Differences between these
      findings and past research suggest that conclusions drawn from adult surgical
      studies cannot be generalized to pediatric patients, especially recent-onset
      samples, without qualification. Differences between the recent-onset and chronic
      samples in this cross-sectional study raise the possibility that
      neurophysiological abnormalities have a cumulative effect on cognitive
      development.

PMID- 15847851
TI  - Hyponatremia in congestive heart failure.
AB  - Hyponatremia has been identified as a risk factor for increased morbidity and
      mortality in patients with congestive heart failure (CHF) and other edematous
      disorders and can lead to severe neurologic derangements. Low cardiac output and
      blood pressure associated with CHF triggers a compensatory response by the body
      that activates several neurohormonal systems designed to preserve arterial blood
      volume and pressure. Hyponatremia in patients with CHF is primarily caused by
      increased activity of arginine vasopressin (AVP). AVP increases free-water
      reabsorption in the renal collecting ducts, increasing blood volume and diluting
      plasma sodium concentrations. Hyponatremia may also be triggered by diuretic
      therapy used in the management of symptoms of CHF. Hyponatremic disorders occur
      when the normal ratio of solutes to body water content is altered by parallel
      changes in serum sodium and osmolality. Hyponatremia is generally defined as a
      serum sodium ion concentration <135 to 136 mmol/L and can be broadly categorized
      into 2 types, dilutional or depletional. Dilutional hyponatremia is the most
      common form of hyponatremia and is caused by excess water retention. Depletional
      hyponatremia is usually hypovolemic, with an absolute deficiency of water but a
      relative excess of body water compared with sodium concentration.

PMID- 15847852
TI  - Neurohormonal activation in congestive heart failure and the role of vasopressin.
AB  - Vasoactive neurohormonal systems (eg, sympathetic nervous system [SNS], renin
      angiotensin-aldosterone system, and arginine vasopressin [AVP]) are defense
      mechanisms designed to preserve arterial volume and circulatory homeostasis
      during periods of low cardiac output. Neurohormonal systems, which are normally
      stimulated under conditions of acute volume depletion, are activated by the low
      cardiac output and arterial pressure. However, sustained and chronic activation
      of these systems, as occurs in congestive heart failure (CHF), can cause
      progressive ventricular remodeling and worsening heart failure. Vasoconstriction,
      water retention, and increased blood volume are results of the activation of the
      SNS, the renin-angiotensin pathway, and AVP secretion. These effects can
      accelerate progression of CHF, contributing to increased morbidity and mortality.
      AVP regulates vascular tone and free-water reabsorption, respectively, through
      the vasopressin V(1a) and V(2) receptor subtypes and therefore is a potential
      neurohormonal target in the treatment of CHF.

PMID- 15847853
TI  - Current treatments and novel pharmacologic treatments for hyponatremia in
      congestive heart failure.
AB  - Hyponatremia in congestive heart failure (CHF) is associated with increased
      morbidity and mortality, underlining the importance of adequate assessment and
      treatment of this electrolyte imbalance in patients with CHF. Current treatment
      options for hyponatremia in CHF include hypertonic saline solution, loop
      diuretics, fluid restriction, and other pharmacologic agents, such as
      demeclocycline, lithium carbonate, and urea. Hypertonic saline solution must be
      administered with extreme caution because excessively slow or rapid sodium
      correction can lead to severe neurologic adverse effects. Loop diuretics are
      useful for reducing the water retention caused by CHF. However, the potent
      diuresis induced by agents such as furosemide results in loss of sodium and other
      essential electrolytes, which may exacerbate hyponatremia. Fluid restriction is
      only moderately effective and often difficult to implement in the hospital
      setting. Agents such as demeclocycline and lithium have potentially serious renal
      and cardiovascular side effects. The arginine vasopressin (AVP) receptor
      antagonists are a promising new class of aquaretic agents that increase free
      water excretion while maintaining levels of sodium and other essential
      electrolytes. Tolvaptan (OPC-41061), lixivaptan (VPA-985), and conivaptan (YM
      087) are currently under development for the treatment of hyponatremia. Although
      tolvaptan and lixivaptan are selective for the vasopressin-2 (V(2)) receptor
      responsible for the antidiuretic actions of AVP, conivaptan demonstrates activity
      at both the V(2) receptor and the V(1a) receptor responsible for the
      vasoconstricting properties of AVP. This dual receptor activity may be
      particularly useful in patients with CHF. These patients may benefit from the
      increased cardiac output, reduced total peripheral resistance, and reduced mean
      arterial blood pressure that results from V(1a) receptor blockade as well as the
      reduced congestion, reduced cardiac preload, and increased sodium concentrations
      induced by V(2) receptor antagonism.

PMID- 15847854
TI  - [Repair of iatrogenic common bile duct laparoscopic injuries: when and how? To be
      careful of the dogma!].

PMID- 15847855
TI  - [Autopsies and surgical service].
AB  - The aim of autopsy is to define the causes of a patient's death by studying the
      gross and microscopic visceral lesions. It is in actual decline but nevertheless
      the post-mortem examination remains one of the basic tools for the assessment of
      medical care in hospital. The aim of this paper is to finalize the present French
      legislation of autopsy and to show its importance in surgical practice.

PMID- 15847856
TI  - [Bile duct injuries at laparoscopic cholecystectomy: early repair results].
AB  - STUDY AIM: To compare the early repair results in bile duct injuries at
      laparoscopic cholecystectomy to a later repair and so the early reconstruction by
      an end-to-end anastomosis to a Roux-en-Y bypass. PATIENTS AND METHOD: From 1990
      to 2003, twelve patients were treated for bile duct injury, not diagnosed at the
      time of cholecystectomy and had an early repair within 30 days after the
      cholecystectomy. They had either a duct to duct anastomosis or a Roux-en-Y bypass
      at the time of the reconstruction. RESULTS: The level of the injury was Bismuth
      II (N=7), III (N=1), IV (N=2) and V (N=1) referral to Bismuth classification and
      one isolated right sectoral duct injury. Four patients had an duct to duct
      anastomosis and eight an hepaticojejunostomy at a median of 15.3 days after
      cholecystectomy. With one patient lost to follow up, the overall success rate in
      this series was 81.8% after reconstruction with a mean 40 months follow up. The
      reconstruction by an end to end anastomosis was successful in 100% of patients
      (with a mean 31.2 months follow up) and in 71.4% of patients after a Roux-en-Y
      biliary reconstruction (with a mean 45 months follow up). CONCLUSION: Good
      results may be performed, by an early repair in bile duct injuries at
      laparoscopic cholecystectomy, either by an duct to duct anastomosis or a Roux-en
      Y bypass.

PMID- 15847857
TI  - [Laparoscopic rectal excision for cancer using total mesorectaol excision (TME).
      Long term outcome of a series of 179 patients].
AB  - BACKGROUND: The purpose of this study was to evaluate the outcomes and the five
      year survival of 179 consecutive patients with rectal carcinoma operated with a
      laparoscopic procedure between April 1992 and April 2003. METHODS: Patients with
      obstructing, bulky cancers were excluded from this study. Tumor stage was defined
      according to the TNM classification. Preoperative radiation therapy was offered
      to T(3) N(0) or N(+) patients (45 Gy). The laparoscopic-assisted technique
      included total mesorectal excision (TME), primary high vascular ligation,
      centrifugal dissection of the mesentery, and "no touch" technique. All the N+
      patients received adjuvant chemotherapy. The outcomes were defined as five-years
      recurrence (local recurrence and distant metastasis) and the diseases-free
      survival. The survival rates were calculated with the Kaplan-Meier test. RESULTS:
      There were 108 males and 71 females, median age was 67 (range 39-88). There were
      61 upper rectum localizations (34%), 68 middle rectum (38%) and 50 low rectum
      (28%). Twenty-nine patients required open conversion (16%). Surgical operative
      morbidity was 24% and medical morbidity was 4%. There were 60 stage I (40%), 25
      stage II (16%), 49 stage III (32%), and 16 stage IV (10%). Ninety patients (71%)
      are alive and disease free, ten (5%) are alive with disease recurrence, and 37
      patients (20%) are deceased. Only one case of trocar site implantation occurred
      after curative resection during an average follow up of 76 months. Five-year
      observed survival rate were 85% for stage I, 70% for stage II, and 63% for stage
      III. CONCLUSION: In our experience laparoscopic rectal resection could be done
      safely. The oncologic outcome was similar to that of open surgery. Further
      randomized trials will be necessary to confirm the value of this technique.

PMID- 15847858
TI  - [Bone integration and apposition of porous and non porous metallic orthopaedic
      biomaterials].
AB  - The objective of this study was to evaluate the functionality of two
      intervertebral fusion implants, a porous nickel-titanium and a conventional
      titanium cage system in a sheep model. Eighteen sheep each received the two
      implant devices at L2-L3 and L4-L5 lumbar levels. The sheep were sacrificed at
      three different postsurgical periods: three, six and 12 months. Lumbar segments
      were harvested. Qualitative (macroscopic and microscopic) and quantitative
      (histomorphometric) histological analysis were carried out on histological
      slides. The results indicated that a porous nickel-titanium had obtained a better
      osseointegration than the titanium implant. The functionality of two implants
      seemed to be influenced by the implant structure and shape. However,
      biocompatibility of two implants seemed comparable.

PMID- 15847859
TI  - [Reinterventions for complication and defect of coloesophagoplasty].
AB  - AIM OF THE STUDY: To report a series of 17 patients operated for a complication
      oesophagocoloplasty, with evaluation of therapeutic modalities, and both early
      and distant results. MATERIALS AND METHOD: From 1985 to 2003, 17 patients with a
      mean age of 50 years (range: 23-76) were reoperated after coloplasty pediculated
      on left superior colic vessels. Initial diseases were caustic ingestion (N=7),
      cancer (N=6), oesophageal perforation (N=2), gastric lymphoma (N=1) and
      oesotracheal fistula (N=1). Coloplasty has been performed as a first-intent
      procedure in 13 cases and as a second-intent procedure after failure of a
      previous operation in 4 cases. Nine patients were initially operated in another
      center and were subsequently referred in our unit. Complications needing
      reoperation were graft necrosis in 8 cases (47%) and stricture in 9 cases (53%).
      All patients with necrosis were reoperated within the 10 first postoperative
      days. RESULTS: Necroses were treated by complete (N=5) or partial (N=3) resection
      of the coloplasty. Strictures were treated by resection-reanastomosis (N=3),
      right ileocoloplasty (N=2), colic stricturoplasty (N=2), a free antebrachial flap
      (N=1) and a tubulized latissimus dorsi myocutaneous pedicled flap (N=1). The 30
      day mortality rate was 12% (N=2) and the overall morbidity rate was 66%. All
      deaths occurred after reoperation for necrosis. Eleven patients (65%) kept or
      recovered digestive continuity (including the 9 with stenosis) and 8 (73%) eat
      normally. Four patients with transplant necrosis died before reestablishment.
      Four patients operated for necrosis died before restoration of digestive
      continuity and 2 patients are still awaiting restoration. CONCLUSION: Use of
      colon as an oesophageal substitute is risky. Reoperations for stenosis allows
      satisfactory oral feeding, while reoperation for necrosis is associated with both
      high early mortality and a low rate of restoration or digestive continuity. This
      later requires a range of complex surgical procedures.

PMID- 15847860
TI  - [How to treat an uncomplicated hydatid liver cyst?].

PMID- 15847861
TI  - [Gallbladder volvulus: two cases report].
AB  - The authors report two cases of gallbladder volvulus. The diagnosis of this rare
      pathology is mainly identified preoperatively. Ultrasonographic findings include
      a "floating gallbladder" with thickened hypoechoic walls. The treatment is
      emergency cholecystectomy.

PMID- 15847862
TI  - [Primary hepatic localization of the PPNET (primitive peripheral neuroectodermal
      tumors). Case report].
AB  - Our purpose is to study, through the case of a patient operated for right hepatic
      tumour, the clinical, radiological, anatomopathologic and therapeutic aspects of
      the peripheral primitive neuroectodermal tumours (PPNET). This tumour (PPNET) is
      a neoplasm belonging to the Ewing's family tumours, whose histology is similar.
      Its diagnosis requires the contribution of histopathology, immunohistochimy and
      cytogenetic studies. The primary hepatic localization of this rare tumour (our
      case), has never been reported. The treatment, in theory copied on that of the
      Ewing's sarcoma, is complex and not yet codified, which makes it another
      disappointing aspect of this disease whose prognosis remains dark.

PMID- 15847863
TI  - [Arterio-ureteral fistula, report of three cases].
AB  - On connection with four cases of arterio-uro-enteric fistula in three patients
      and after a review of the literature, the authors propose to make light on this
      extremely rare complication describing aetiologies factors and the diagnostic
      means and therapeutics. Two patients had had a pelvic exenteration with
      respectively Bricker and Kock pouch. The third patient had had an anterior
      resection in block with the right deferent duct and right seminal gland. All
      three received high doses of radiotherapy. These fistulas had appeared by
      abundant haemorrhages. The surgical operation in urgency had made it possible to
      treat these fistulas with success in two patients. The other patient had deceased
      of cataclysmic haemorrhage.

PMID- 15847864
TI  - [Peroperative rescue procedure after failure of oesophagojejunostomy following
      total gastrectomy].
AB  - Leakage of oesophagojejunostomy is a severe complication of total gastrectomy. We
      present a technique allowing preoperative preservation of a defective
      oesophagojejunostomy: this technique involves closure of the cervical esophagus
      with stapler, double-lumen transanastomotic tube, mediastinal drainage and
      feeding jejunostomy.

PMID- 15847865
TI  - [Preparation of the perioperative environment in surgery for pheochromocytoma].

PMID- 15847866
TI  - [Problems in pheochromocytoma diagnosis].

PMID- 15847867
TI  - [Bilateral pheochromocytoma. Genetics and treatment].

PMID- 15847868
TI  - Myomectomy during cesarean section.
AB  - OBJECTIVE: To evaluate the outcome of myomectomy during cesarean section and to
      compare it with a control group. MATERIALS AND METHODS: Using a retrospective
      case-control design; 40 patients who underwent myomectomy at time of cesarean
      delivery were compared with the control group consisted of 80 patients with
      myomas who underwent cesarean delivery alone. RESULTS: The mean size of fibroids
      removed was 8.1+/-4.7 cm (range, 3-25 cm). In control group it was 5.7+/-2.7 cm
      (range, 2-14 cm). The incidence of hemorrhage in the study group was 12.5% as
      compared with 11.3% in the control group (p>0.05). There was also no significant
      differences in the incidence of postoperative fewer and frequency of blood
      transfusion between myomectomy and control groups (p>0.05). CONCLUSION:
      Myomectomy during cesarean section is not always a hazardous procedure and it can
      be performed without significant complications by experienced obstetricians.

PMID- 15847869
TI  - A predictive model for cesarean section in low risk pregnancies.
AB  - OBJECTIVE: A small number of women with low risk pregnancies undergo cesarean
      section. A model that can predict this risk and therefore identify these women
      will be of help in several hospitals where personnel and resources are limited.
      METHODS: The study consisted of 2 parts. All charts of women with low risk
      singleton pregnancies admitted to labor room over a 5-month period were analyzed.
      Adjusted odds ratios were calculated to find out relative importance of each risk
      factor and likelihood ratios were obtained. These were prospectively applied to
      1010 consecutive low risk women and the post test probability calculated. Finally
      the actual incidence of cesarean section was compared with posttest probability
      derived from predictors. RESULTS: A combination of maternal age >24 years,
      primiparity and height <150 cm or a combination of any 2 of the 3 variables is
      significantly associated with increased cesarean section rate. Individually,
      primiparity, height <150 cm or age >24 years also significantly increased the
      chances of cesarean section. CONCLUSIONS: A predictive model consisting of
      maternal age, parity and height can be used to identify low risk pregnant women
      who are likely to require cesarean section.

PMID- 15847870
TI  - Outcome of congenital cystic adenomatoid malformation of the lung after antenatal
      diagnosis.
AB  - OBJECTIVE: We evaluated the outcome of fetuses diagnosed with having congenital
      cystic adenomatoid malformation (CCAM) on ultrasonographic examination and
      managed conservatively. METHODS: A retrospective study of 19 cases of CCAM
      diagnosed antenatally in our hospital was conducted between 1990 and 2001.
      Complete clinical information was available for all patients, with a mean follow
      up of 62 months. RESULTS: The median gestational age at which CCAM was diagnosed
      was 23 weeks and there were eight live births. With conservative postnatal
      management, seven neonates had no major complications and one developed
      bronchopneumonia. CONCLUSION: Taken together, the findings of the present study
      and a review of the literature strongly support the conservative management of
      selected neonates with CCAM.

PMID- 15847871
TI  - Expression of endothelial nitric oxide synthase traffic inducer in the placentas
      of women with pre-eclampsia.
AB  - OBJECTIVE: To investigate the expression of endothelial nitric oxide synthase
      traffic inducer (NOSTRIN) in the placenta of women with pre-eclampsia (PE) and
      discuss its role in the pathogenesis of PE. METHODS: Western blot analysis was
      used to detect the expression of NOSTRIN and endothelial nitric oxide synthase
      (eNOS). The activity of eNOS in placental tissue was assayed by
      spectrophotometry. Serum and placental NO(2)/NO(3), the stable metabolic end
      product of NO, was measured using nitrate reductase. RESULTS: Western blot
      analysis showed that the protein level of NOSTRIN was significantly higher in
      women with PE than in the control group (P<0.01). However, no significant
      difference between groups was observed in the expression of placental eNOS
      (P>0.05). The activity of eNOS was significantly decreased in women with PE
      (13.727+/-3.58 U/mg) compared with the control group (21.69+/-3.84 U/mg)
      (P<0.01). The placental levels of NO(2)/NO(3) were significantly lower in women
      with PE (27.53+/-8.51 micromol/mg) than in the control group (44.38+/-9.59
      micromol/mg) (P<0.01). The levels of serum NO(2)/NO(3) were significantly lower
      in women with PE (48.56+/-8.49 micromol/L) than in the control group (65.37+/
      9.61 micromol/L) (P<0.01). A significant negative correlation existed between the
      expression of NOSTRIN protein and the activity of eNOS in the placental tissues
      of women with PE (r=-0.57, P<0.01). CONCLUSION: The level of NOSTRIN expression
      in the placental tissues of women with PE is increased and is negatively
      correlated with the activity of eNOS-which may play an important role in the
      pathogenesis of PE.

PMID- 15847872
TI  - Artificial neural network computer prediction of ovarian malignancy in women with
      adnexal masses.
AB  - OBJECTIVE: Assessment of the usefulness of a neural model to predict which
      ovarian tumors are malignant. METHOD: Age, menopausal status, body mass index,
      grayscale and Doppler ultrasonographic features, as well as levels of specific
      markers (CA 125, tissue polypeptide specific antigen) were examined in 686 women
      with adnexal masses. The probability of malignancy was calculated using an
      artificial neural network software and the diagnostic efficiency of the received
      model was estimated using a receiver-operating characteristics (ROC) curve.
      RESULT: Of the 686 women, 431 (62.8%) had a benign and 255 (37.2%) had a
      malignant ovarian tumor. The significant malignancy predictors are age,
      menopausal status, maximum tumor diameter, internal wall structure of tumor,
      presence of septa and/or solid elements, tumor location, location of vessels, and
      blood flow indexes. The best network provided 96.0% sensitivity and 97.7%
      specificity. The area under the curve for the received model was 0.9716.
      CONCLUSIONS: An artificial neural network model based on clinical and
      ultrasonographic data allows to calculate the probability of tumor malignancy.

PMID- 15847873
TI  - Diagnosis and management of uterine arteriovenous fistulas with massive vaginal
      bleeding.
AB  - OBJECTIVE: To study the clinical manifestations, diagnosis, management, and
      prognosis of uterine arteriovenous fistulas with massive vaginal bleeding.
      METHODS: The clinical records of 15 patients who satisfied the diagnostic
      criteria were retrospectively analyzed. RESULTS: All patients had massive vaginal
      bleeding and a history of cesarean section, curettage, or gynecologic carcinoma.
      The disease was diagnosed by angiography or color Doppler ultrasonography.
      Vaginal bleeding can be aggravated by dilation and curettage. No complications
      occurred in the 14 patients who were treated with uterine artery embolization. Of
      the 11 patients who underwent successful embolizations, all returned to a normal
      menstrual cycle and 5 later became pregnant. CONCLUSION: Uterine arteriovenous
      fistula is a rare and potentially life-threatening condition. Uterine artery
      embolization is a safe and effective choice of treatment for this condition, and
      it can preserve both uterus and ovary function.

PMID- 15847874
TI  - Comparison of pap smear, visual inspection with acetic acid, human papillomavirus
      DNA-PCR testing and cervicography.
AB  - OBJECTIVE: To assess the test qualities of four screening methods to detect
      cervical intra-epithelial neoplasia in an urban African setting. METHOD: Six
      hundred fifty-three women, attending a family planning clinic in Nairobi (Kenya),
      underwent four concurrent screening methods: pap smear, visual inspection with
      acetic acid (VIA), PCR for high risk human papillomavirus (HR HPV) and
      cervicography. The presence of cervical intra-epithelial neoplasia (CIN) was
      verified by colposcopy or biopsy. RESULT: Sensitivity (for CIN2 or higher) and
      specificity (to exclude any CIN or cancer) were 83.3% (95% CI [73.6, 93.0]) and
      94.6% (95% CI [92.6, 96.5]), respectively, for pap smear; 73.3% (95% CI [61.8,
      84.9]) and 80.0% (95% CI [76.6, 83.4]) for VIA; 94.4% (95% CI [84.6, 98.8]) and
      73.9% (95% CI [69.7, 78.2]) for HR HPV; and 72.3% (95% CI [59.1, 85.6]) and 93.2%
      (95% CI [90.8, 95.7]) for cervicography. CONCLUSION: The pap smear had the
      highest specificity (94.6%) and HPV testing the highest sensitivity (94.4%). The
      visual methods, VIA and cervicography, were similar and showed an accuracy in
      between the former two tests.

PMID- 15847876
TI  - Pregnancy outcomes in in vitro fertilization cycles with serum estradiol drop
      prior to human chorionic gonadotropin.
AB  - OBJECTIVE: To study the effect of an unpredictable drop in serum estradiol prior
      to hCG administration on pregnancy outcomes in in vitro fertilization cycles.
      METHODS: 3653 consecutive IVF cycles from January 1, 1998 to December 31, 2000 at
      Brigham and Women's Hospital were reviewed, and 65 cycles in which oocyte
      retrieval (ER) was performed following a drop in serum estradiol (E(2)) not
      associated with intentional withdrawal of gonadotropins were identified. Daily
      gonadotropin dose was decreased at some time in 25 of these cycles, while the
      remaining 40 cycles did not have a reduction in gonadotropin dose. A
      retrospective case-control study of the respective live birth rates and pregnancy
      loss rates of patients with unpredictable E(2) drops in the 65 study cycles were
      compared to 65 age matched controls. RESULTS: Live birth rates (32% vs. 35%,
      p=0.72) and pregnancy loss rates (28% vs. 30%, p=0.76) were similar for all study
      and control groups respectively. There were no differences in live birth and
      pregnancy loss rates in cycles undergoing gonadotropin dose reduction (40% vs.
      44%, p=0.78 and 29% vs. 39%, p=0.70) and cycles without gonadotropin dose
      reduction (28% vs. 30%, p=0.81 and 27% vs. 20%, p=0.72). CONCLUSIONS: In the
      absence of coasting, a drop in serum estradiol levels during GnRH-agonist
      downregulated controlled ovarian hyperstimulation for IVF prior to hCG is not
      associated with a decrease in live birth rates or pregnancy loss rates.

PMID- 15847875
TI  - Propolis solution for the treatment of chronic vaginitis.
AB  - OBJECTIVE: To evaluate the efficacy of 5% propolis solution in recurrent
      vaginitis. METHOD: Fifty-four patients with recurrent vaginal infections having
      undergone at least one cycle of antibiotic treatment were instructed to apply a
      5% aqueous propolis solution as a vaginal douche for seven days. Vaginal smears
      and specific symptoms were evaluated at baseline and 14 days after treatment.
      Long-term well-being was assessed by telephone interview six months after follow
      up. RESULT: At the follow-up, the vaginal smears of 41 patients (75.9%) had
      improved. Forty-seven patients (87%) reported reliefs concerning at least one
      complaint. Associated improvement of smear and well-being was observed in 36
      women (66.7%). After 6 months, 33 patients (61.1%) were satisfied with their
      condition without having undergone further treatment. CONCLUSION: Propolis may
      have a role as an alternative treatment for chronic vaginal infection.

PMID- 15847877
TI  - Urinary levels of nuclear matrix protein-22 in pregnant and non-pregnant women.

PMID- 15847878
TI  - Twin gestation after ovulation induction in a woman with a non-communicating
      rudimentary horn attached to a unicornuate uterus.

PMID- 15847879
TI  - Oral misoprostol vs. vaginal misoprostol for cervical ripening and labor
      induction.

PMID- 15847880
TI  - Post-cesarean section acute colonic pseudo-obstruction with spontaneous
      perforation.

PMID- 15847881
TI  - Management of prolapsed pedunculated myomas.

PMID- 15847882
TI  - Pyramidalis muscle endometriosis in absence of previous surgery.

PMID- 15847883
TI  - Lateral distribution of benign ovarian cysts.

PMID- 15847884
TI  - Human vaginal myiasis caused by Cochliomyia hominivorax.

PMID- 15847885
TI  - Management of massive uterine bleeding in a cesarean scar pregnancy.

PMID- 15847886
TI  - Treatment of abnormal uterine bleeding with micronized flavonoids.

PMID- 15847887
TI  - Evaluation of mastodynia in postmenopausal women taking hormone therapy.

PMID- 15847888
TI  - Activin A levels in serum and cyst fluid in epithelial tumors of the ovary.

PMID- 15847889
TI  - Treatment of viable cesarean scar ectopic pregnancy with suction curettage.
AB  - OBJECTIVE: Pregnancy in previous cesarean scar is the rarest form of ectopic
      pregnancy. All reported cases in the literature that were treated with uterine
      curettage either become unsuccessful or complicated. We aimed to present a case
      of cesarean scar ectopic pregnancy that was successfully treated with suction
      curettage without any additional therapy. CASE: A 32-year-old asymptomatic woman,
      gravida 2, para 1 was referred to our hospital with the possible diagnosis of
      cervical ectopic pregnancy. Transvaginal and transabdominal sonographic
      examination revealed the diagnosis of viable ectopic pregnancy in a previous
      cesarean scar. Suction curettage with carman canulles was performed under
      transabdominal ultrasonographic guidance. beta-hCG decreased progressively
      postoperatively. CONCLUSION: Suction curettage under ultrasonography guidance can
      be used in termination of selected cases (early diagnosed, without symptoms that
      necessitates emergency intervention) of cesarean scar pregnancy.

PMID- 15847890
TI  - Visual inspection with acetic acid and cytology as screening methods for cervical
      lesions in Cameroon.
AB  - OBJECTIVES: To assess the accuracy of visual inspection with acetic acid (VIA) as
      a screening method for cervical lesions. METHODS: VIA and cytological smears were
      carried out on the cervices of non-pregnant women aged 30-60 years with no
      previous history of cervical cancer. Cervices with aceto white lesions or
      positive Pap smears, and one in ten negative cervices (control), were biopsied.
      RESULTS: 5010 women were enrolled, 4813 (96.1%) were screened. 4767 (99.%) had
      adequate cytology smears. 574 (11.9%) had colposcopy. 1743 biopsies were obtained
      of which 528 were controls. The sensitivity of VIA was 70.4% versus 47.7% for Pap
      smear. VIA specificity was 77.6% versus 94.2% for Pap smear; PPV for VIA was
      44.0% versus 67.2% for Pap smear; and NPV for VIA was 91.3% versus 87.8% for Pap
      smear. CONCLUSIONS: VIA has acceptable test qualities and may in low resource
      settings be implemented as a large scale screening method.

PMID- 15847891
TI  - Childbirth in Palestine.
AB  - OBJECTIVE: This study describes staffing, caseloads and reported routine
      practices for normal childbirth in Palestinian West Bank (WB) governmental
      maternity facilities and compares these practices with evidence-based care.
      METHODS: Data on routine childbirth practices in all eight governmental hospitals
      were obtained through interviews with head obstetricians and midwives. Data on
      staffing and monthly number of births were collected by phone or personal
      interview from all 37 WB hospitals. RESULTS: Forty-eight percent of WB deliveries
      took place in crowded and understaffed governmental hospitals. Reported practices
      were not consistently in line with evidence-based care. Lack of knowledge and
      structural barriers were reasons for this gap. CONCLUSION: The implications of
      limiting unnecessary interventions in the normal birth process are particularly
      important in a context of limited access and scarce resources. More skilled birth
      attendants and a universal commitment to effective care are needed.

PMID- 15847892
TI  - Adolescents and consent to treatment.
AB  - Adolescents, defined by WHO as 10 to 19 years old, can give independent consent
      for reproductive health services if their capacities for understanding have
      sufficiently evolved. The international Convention on the Rights of the Child,
      almost universally ratified, limits parental powers, and duties, by adolescents'
      "evolving capacities" for self-determination. Legal systems may recognize "mature
      minors" as enjoying adult rights of medical consent, even when consent to sexual
      relations does not absolve partners of criminal liability; their consent does not
      make the adolescents offenders. There is usually no chronological "age of
      consent" for medical care, but a condition of consent, meaning capacity for
      understanding. Like adults, mature minors enjoy confidentiality and the right to
      treatment according to their wishes rather than their best interests. Minors
      incapable of self-determination may grant or deny assent to treatment for which
      guardians provide consent. Emancipated minors' self-determination may also be
      recognized, for instance on marriage or default of adults' guardianship.

PMID- 15847893
TI  - Averting maternal death and disability.

PMID- 15847894
TI  - A tool for assessing 'readiness' in emergency obstetric care: the room-by-room
      'walk-through'.
AB  - This article presents a tool that can be used to assess the readiness of a health
      facility to provide emergency obstetric care. The 'walk-through' tool is a
      checklist that follows the physical path that a woman and her caregivers might
      follow. The items on the checklist are critical to an enabling environment in
      which skilled providers can save lives. The article explains how the tool can be
      used and by whom, and it describes several experiences in the field.

PMID- 15847895
TI  - Skilled birth attendance: what does it mean and how can it be measured? A
      clinical skills assessment of maternal and child health workers in Nepal.
AB  - The presence of a skilled birth attendant at delivery is important in averting
      maternal and neonatal mortality and morbidity. It has now shown that even trained
      traditional birth attendants (TBAs) cannot, in most cases, save women's lives
      effectively because they are unable to treat complications, and are often unable
      to refer. Qualified midwives and doctors are often not available in the rural
      areas and community settings where most women in developing countries deliver.
      Defining the minimum competency level necessary to meet the definition of skilled
      birth attendant is important, particularly in countries such as Nepal with
      limited availability of facility-based emergency obstetric care. Maternal and
      child health workers are local women aged 18-35 who completed a 15-week course in
      maternal and child health. As the role of MCHWs has expanded to meet the
      country's needs for skilled attendance, a 6-week "refresher" course in midwifery
      skills is offered. The results of this clinical skills assessment of 104 randomly
      selected MCHWs from 15 districts across Nepal supports the premise that MCHWs
      with appropriate training have an acceptable level of knowledge and skill,
      demonstrated in a practice situation, to meet the definition of community level
      skilled birth attendants. Yet, competency alone will not necessarily improve the
      situation. To affect maternal mortality in Nepal, MCHWs must be widely available,
      they must be allowed to do what they are trained to do, and they must have
      logistical and policy support.

PMID- 15847896
TI  - Monitoring utilization and need for obstetric care in the highlands of Guatemala.
AB  - OBJECTIVE: To monitor changes in the utilization and need for obstetric care
      between 1995 and 1998 at three hospitals in the highlands of Guatemala. METHODS:
      We collected data on 5300 obstetric admissions from maternity registries and
      selected 10 indicators to measure intermediate outcomes. RESULTS: Utilization of
      services increased at some or all hospitals as measured by the number of
      obstetric admissions, proportion of births in facilities, and cesarean deliveries
      as a proportion of all births. We observed increases in the proportion of women
      expected to have obstetric complications who were treated at each hospital and in
      the proportion of women with obstetric complications who were referrals. The
      changes in patient profile reflect increased service utilization and
      accessibility among women who traditionally used the health system the least.
      CONCLUSIONS: Positive changes in these indicators are likely to be associated
      with a reduction in maternal mortality. Without a control area, we cannot be sure
      of a cause and effect relationship between outcomes and interventions,
      nevertheless, maternity registry data offer an inexpensive source of information
      for facilities to monitor changes.

PMID- 15847897
TI  - Research note: Estimating maternal deaths averted: A field-based methodology.

PMID- 15847898
TI  - Program note: Using UN process indicators to assess needs in emergency obstetric
      services: Bolivia, El Salvador and Honduras.
AB  - The UN process indicators are used to assess the availability, utilization and
      quality of emergency obstetric care (EmOC). Needs assessments for EmOC in
      Bolivia, El Salvador and Honduras show reasonable availability of comprehensive
      EmOC facilities for their population sizes, but a scarcity of basic facilities.
      Utilization rates among women with obstetric complications are high in El
      Salvador and Honduras. Case fatality rates tend to be below 1% in all three
      countries, but the more rural areas in each have poorer indicators.

PMID- 15847899
TI  - Science and art in reviewing literature.

PMID- 15847900
TI  - The experience of fatigue, other symptoms and global quality of life during
      radiotherapy for uterine cancer.
AB  - This paper reports on how patients with uterine cancer, receiving radiotherapy,
      experience fatigue, other symptoms and global quality of life. The results showed
      that fatigue increased significantly during the therapy. Also the other symptoms;
      loss of appetite, nausea/vomiting and diarrhoea increased significantly and were
      significantly correlated to general fatigue. Global quality of life decreased
      significantly during treatment compared to baseline. The variation of the level
      in general fatigue after completed therapy was only explained by the level of
      general fatigue experienced at baseline. The result can lead to a better
      understanding of the severity of symptoms experienced by patients with uterine
      cancer treated with radiotherapy.

PMID- 15847901
TI  - The effect of type of hip protector and resident characteristics on adherence to
      use of hip protectors in nursing and residential homes--an exploratory study.
AB  - OBJECTIVES: To investigate the factors influencing the acceptability of hip
      protectors to residents of nursing and residential homes, especially the effect
      of hip protector type, and resident characteristics. DESIGN: A randomised
      controlled trial with 12 weeks follow-up. Participants were randomised to receive
      either Safehip or HipSaver hip protectors. SETTING/PARTICIPANTS: 109 residents
      aged 61 to 98 years from seven residential homes and two nursing homes in
      Northern Ireland. MAIN OUTCOME MEASURES: Percentage day-time use of the hip
      protectors over 12 weeks and ongoing use at 12 weeks. RESULTS: 42% (119/285) of
      residents invited to enter the study agreed to take part, and 109 started to wear
      the hip protectors. 43.1% (47/109) were still using them at 12 weeks. Mean
      percentage day-time use for all residents during 12 weeks was 48.6%. There was no
      significant difference in percentage day-time use (p=0.40), or use at 12 weeks
      (p=0.56) between the residents wearing Safehip and HipSaver protectors. Greater
      percentage daytime use of hip protectors was associated with being resident in a
      home for the elderly mentally infirm (75.1%, p<or=0.0005), having a low (12 or
      less) Barthel score (61.1%, p<or=0.0005), and having been injured in a fall in
      the last 12 months (57.3%, p=0.012). CONCLUSIONS: The type of hip protector
      appeared to make no difference to their continued use by residents. Residents
      with a history of a fall and those who are physically and mentally incapacitated
      appear to be more likely to wear hip protectors. These residents, who are at high
      risk of falling, are also highly dependent on nursing staff. Efforts to increase
      hip protector use in residential and nursing home should focus on staff, who are
      in the best position to advise and influence residents and their relatives.

PMID- 15847902
TI  - Characteristics of the grieving process: a pilot study of 10 Korean spouses of
      patients who passed away from cancer.
AB  - The purpose of this descriptive study was to identify the characteristics of the
      grieving process of Korean spouses who lost their partner to cancer. Five women
      and five men were recruited by convenience sampling from surviving spouses
      attending a follow up program at a hospice center in Seoul, Korea. In-depth
      interviews, observation, and instruments on grief stage and grief responses were
      used to collect data. Interviews were tape recorded, transcribed, and analyzed
      line by line to discover recurrent patterns and themes. Gender differences were
      noted for grief responses (physical, cognitive, emotional, social and spiritual)
      and factors influencing grief.

PMID- 15847903
TI  - Evaluation of the breastfeeding intervention program in a Korean community health
      center.
AB  - A new model for the breastfeeding intervention program was implemented in a
      Korean community health center and the effectiveness of the program was
      evaluated. Thirty health care personnel from 29 smaller community health centers
      and 23 breastfeeding helpers were trained in four workshops. They then gave
      information on breastfeeding to pregnant and lactating women, living in each
      community in groups or individually. The breastfeeding rate after intervention
      has significantly increased at 1 week and 9 months of age. These results indicate
      that the community-based breastfeeding intervention program by training both the
      health care professionals and peer helpers is effective in promoting
      breastfeeding.

PMID- 15847904
TI  - The role of community nurses for people with learning disabilities: working with
      people who challenge.
AB  - The locus of care for people with learning disabilities has transferred from
      institutional to community-based services. Increasingly people who have learning
      disabilities and additional challenging behaviours live in community settings.
      Spearheading the care for these people are community nurses for people with
      learning disabilities. This study aimed to explicate the role of these nurses in
      their day-to-day work with people who challenge. Using grounded theory
      methodology, 22 nurses were selected by theoretical sampling and interviewed. An
      analytical story and theoretical framework that emerged from the grounded data is
      presented. It is suggested that this framework has utility for practice.

PMID- 15847905
TI  - Physician-nurse attitudes toward collaboration in Istanbul's public hospitals.
AB  - The need for greater collaboration between nurses and physicians in clinical
      practice is essential to improve patient care and worker satisfaction. This study
      used t-tests and logistic regression to test four research hypotheses concerning
      attitudes toward physician-nurse collaboration in Istanbul, Turkey. The study
      found that nurses express more positive attitudes toward collaboration than
      physicians. Noteworthy was the finding that male physicians expressed more
      positive attitudes toward collaboration than female physicians. Residents and
      those employed in secondary institutions were also more likely to express more
      positive attitudes toward collaboration than permanent physicians and those
      employed in tertiary hospitals.

PMID- 15847906
TI  - Perinatal grief and emotional labour: a study of nurses' experiences in gynae
      wards.
AB  - Death through pregnancy loss is a tragedy which touches nursing staff as well as
      parents. Exposed to the intense emotions of parents, nurses must simultaneously
      manage their own emotions. This paper explores how nurses, through the use of
      personal narratives, develop and construct meanings around the professionally
      defined, but personally experienced, event of pregnancy loss. The methodology was
      based on in-depth interviews with fourteen nurses working in gynaecological units
      in Northern Ireland. The author, through the exploration of the nurse's
      perspective, concludes that emotion can be conceived of as a valid resource for
      professionals when integrated into a nurse's matrix of professional
      understandings. In addition, the study also demonstrates that value should be
      attached to emotional work which may not be fully visible, particularly for
      nurses working in gynaecological units. The emotional needs of nurses need to be
      fully acknowledged through recognition of the importance of managed emotion in
      the construction of professional knowledge. There is, therefore, strong
      justification for supporting the recognition of the importance of emotion in the
      development of nurse education policies and in valuing aspects of nursing
      practice that may have been marginalized.

PMID- 15847907
TI  - Feeding back survey research findings within palliative care. Findings from
      qualitative research.
AB  - The feedback of research findings to practitioners and policy makers is an
      important component of palliative care research. Little is, however, understood
      about professionals' views on the ways research findings should be fed back. This
      study used semi-structured telephone interviews with a vignette to understand
      professionals' views on the feedback of survey research findings within
      palliative care. Content analysis of data uncovered a range of issues
      professionals emphasised as important to consider. These issues are discussed
      within the context of existing literature in order to raise the profile of
      research feedback within palliative care.

PMID- 15847908
TI  - Development and psychometric properties of the Chinese language version of the
      TAPQOL: a health-related quality of life instrument for preschool children.
AB  - The objectives of this study were to assess psychometric properties of the
      Mandarin version of the TZO-AZL Preschool Children Quality of Life (TAPQOL)
      questionnaire in Taiwanese preschool children. Two groups of children, a very low
      birthweight group (n=118) and a not-very low birthweight group (n=170), were
      recruited. The internal consistency was acceptable and the correlation
      coefficients between the 12 subscales were low. Confirmatory factor analysis
      supported the 12-factor structure. Children with very low birthweight had
      significantly lower quality of life scores. This instrument may be used in
      clinical and research applications to investigate quality of life among preschool
      children.

PMID- 15847909
TI  - An international comparative study on the reliability and validity of the
      attitudes towards aggression scale.
AB  - One of the factors known to be associated with the management of patient
      aggression is the attitude of staff members towards the aggressive behaviour of
      patients. The construct validity of an instrument measuring the attitudes of
      staff towards inpatient aggression in psychiatry was evaluated in this
      international multi-centre study. Factor analysis and simultaneous component
      analysis were performed with data from a convenience sample of 1769 psychiatric
      nurses working in psychiatric hospitals and student nurses from nursing schools.
      The samples were recruited by fellow researchers in their home country. The
      original 32-item version (POAS) was reduced to 18 items comprising five attitude
      scales with solid psychometric properties. The types of attitudes were labelled
      offensive, communicative, destructive, protective and intrusive. The format of
      the correlations between the types of attitudes suggested the existence of two
      basic underlying divergent domains in the scale. The 'communication' and
      'protection' scale components on the one hand, and the 'offence', 'destruction'
      and 'intrusion' components on the other. The five types of attitude proved to be
      invariant across samples from five European countries. The Aggression Scale
      (ATAS) is a reliable and valid measure that will enable researchers to perform
      international comparative research on attitudes and aggression.

PMID- 15847910
TI  - The role of the nurse in community continence care: a systematic review.
AB  - Urinary incontinence (UI) is a condition that is associated with decreased
      quality of life. Apart from this impact on quality of life, UI is also a very
      costly problem. It is recognised that 'usual care' for patients suffering from UI
      is not optimal. Specialised nurses can play an important role in the care for
      community-dwelling incontinent patients, as they have the appropriate
      interpersonal and technical skills to provide patient-tailored care. This
      systematic review analyses the effect of treatment by nurses on clinical and
      economic outcomes. A total of 12 randomised controlled trials (RCTs) were found,
      varying in terms of population, setting, outcome measurement and
      control/intervention. There is limited evidence that treatment by nurses results
      in a decrease in incontinence. No evidence was found for cost reduction.
      Recommendations are made for future studies.

PMID- 15847911
TI  - Assessing the quality of life--reality or impossible dream? A discussion paper.
AB  - Many now claim that maintaining or improving the quality of life is the essence
      of healthcare (i.e. care and/or treatment that improves the patients' quality of
      life). Interest in QL, however, stems from increasing recognition that
      individuals are an integrated whole rather than a series of disconnected parts or
      disease states. Though this represents a significant change from the past--when
      the emphasis lay solely on physical or medical condition--it is not, in itself,
      meaningful unless reliable and valid ways of evaluating the human aspects of the
      experience can be identified (i.e. quality of life). As quality of life (QL) is
      seen as a positive state, a desirable outcome of healthcare interventions, it has
      gained credence as an appropriate outcome measure and has intuitive appeal.
      Indeed, it is suggested that, because of its close relationship to mortality,
      self-perceived QL may be the most important outcome of both acute and,
      particularly, chronic disease. Lack of consensus about its meaning has, however,
      resulted in ambiguity and, therefore, difficulties in its measurement reflecting,
      in turn, the difficulty in identifying the components of this multifaceted
      concept. This paper explores these issues and questions whether we are, in fact,
      attempting to measure something that cannot truly be measured.

PMID- 15847912
TI  - Diurnal biting periodicity of parous Simulium (Diptera: Simuliidae) vectors in
      the onchocerciasis Amazonian focus.
AB  - We describe the hourly patterns of parous biting activity of the three main
      simuliid vectors of human onchocerciasis in the Amazonian focus straddling
      between Venezuela and Brazil, namely, Simulium guianense s.l. Wise; S.
      incrustatum Lutz, and S. oyapockense s.l. Floch and Abonnenc. Time series of the
      hourly numbers of host-seeking parous flies caught in five Yanomami villages
      during dry, rainy, and their transition periods from 1995 to 2001 were
      investigated using harmonic analysis (assuming an underlying circadian rhythm)
      and periodic correlation (based on Spearman's r). Parous S guianense s.l. showed
      a bimodal activity pattern, with a minor peak in mid-morning and a major peak at
      16:00 h. S. incrustatum exhibited mainly unimodal activity during either early
      morning or midday according to locality. S. oyapockense s.l. bit humans
      throughout the day mainly between 10:00 and 16:00 h but also showed bimodal
      periodicity in some localities. Superimposed on the endogenous, species-specific
      daily cycles, parous activity showed variation according to locality, season, air
      temperature and relative humidity, with biting being promoted by warmer and drier
      hours during wet seasons/periods and reduced during hotter times in dry seasons
      or transitions. The results are discussed in terms of their implications for
      blackfly biology and ecology as well as onchocerciasis epidemiology and control.

PMID- 15847913
TI  - Development and evaluation of a multiplex PCR for differentiation of foot-and
      mouth disease virus strains native to India.
AB  - A multiplex PCR (mPCR) for the differentiation of Indian FMDV serotypes, O, A,
      Asia 1 and C was developed and evaluated on 142 clinical and 39 cell culture
      samples. On the latter samples both the tests worked well with 100% efficiency,
      whereas on clinical samples mPCR had better efficiency than ELISA. The test was
      found to be specific for FMDV. The detection limit of the assay was varied among
      the serotypes; it was most sensitive on types A and Asia 1 and least sensitive on
      type C. The mPCR clearly identified the serotype and in some cases detected dual
      infections. The test is sensitive and reliable and can be used for serotyping of
      ELISA negative samples.

PMID- 15847914
TI  - Virus-inducible reporter genes as a tool for detecting and quantifying influenza
      A virus replication.
AB  - The use of influenza A virus-inducible reporter gene segments in detecting
      influenza A virus replication was investigated. The RNA polymerase I
      promoter/terminator cassette was used to express RNA transcripts encoding green
      fluorescence protein or firefly luciferase flanked by the untranslated regions of
      the influenza A/WSN/33 nucleoprotein (NP) segment. Reporter gene activity was
      detected after reconstitution of the influenza A virus polymerase complex from
      cDNA or after virus infection, and was influenza A virus-specific. Reporter gene
      activity could be detected as early as 6 h post-infection and was virus dose
      dependent. Inhibitory effects of antibodies or amantadine could be detected and
      quantified rapidly, providing a means of not only identifying influenza A virus
      specific replication, but also of determining the antigenic subtype as well as
      antiviral drug susceptibility. Induction of virus-specific reporter genes
      provides a rapid, sensitive method for detecting virus replication, quantifying
      virus titers and assessing antiviral sensitivity as well as antigenic subtype.

PMID- 15847915
TI  - The use of endogenous and exogenous reference RNAs for qualitative and
      quantitative detection of PRRSV in porcine semen.
AB  - Semen is known to be a route of porcine reproductive and respiratory syndrome
      virus (PRRSV) transmission. A method was developed for qualitative and
      quantitative detection of the seminal cell-associated PRRSV RNA in relation to
      endogenous and exogenous reference RNAs. As endogenous control for one-step real
      time reverse transcription (RT)-PCR UBE2D2 mRNA was selected. Particularly for
      the analysis of persistent infections associated with low copy numbers of PRRSV
      RNA, UBE2D2 mRNA is an ideal control due to its low expression in seminal cells
      and its detection in all samples analysed (n = 36). However, the amount of UBE2D2
      mRNA in porcine semen varied (up to 106-fold), thus its use is limited to
      qualitative detection of PRRSV RNA. For quantitation, a synthetic, non-metazoan
      RNA was added to the RNA isolation reaction at an exact copy number. The
      photosynthesis gene ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit
      (rbcL) from Arabidopsis thaliana was used as an exogenous spike. Unexpectedly,
      PRRSV RNA was detected in a herd of specific pathogen-free (SPF) boars which were
      tested ELISA-negative for anti-PRRSV antibodies. Therefore, RT-PCR for seminal
      cell-associated PRRSV is a powerful tool for managing the SPF status during
      quarantine programs and for routine outbreak investigations.

PMID- 15847916
TI  - Modification of liposomal concentration in liposome/adenoviral complexes allows
      significant protection of adenoviral vectors from neutralising antibody, in
      vitro.
AB  - Adenoviral vectors have been commonly used in gene therapy protocols, however the
      success of their use is often limited by the induction of host immunity to the
      vector. Following exposure to the adenoviral vector, adenoviral-specific
      neutralising antibodies are produced which limits further administration. This
      study examines the efficacy of complexing liposomes to adenovirus for the
      protection of the adenovirus from neutralising antibodies in an in vitro setting.
      Dimethyldioctadecylammonium bromide (DDAB)-dioleoyl-l-phosphatidylethanolamine
      (DOPE) liposomes were bound at varying concentrations to adenovirus to form AL
      complexes and tested these complexes' ability to prevent adenoviral
      neutralisation. It is shown that by increasing the concentration of liposomes in
      the adenoviral-liposome (AL) complexes we can increase the level of immuno
      shielding afforded the adenovirus. It is also shown that the increase in
      liposomal concentration may lead to drawbacks such as increased cytotoxicity and
      reductions in expression levels.

PMID- 15847917
TI  - JC virus genotyping using formalin-fixed, paraffin-embedded renal tissues.
AB  - Recently genotyping of JC virus (JCV) DNA in renal tissue was reported to be
      useful to identify the geographic origin of unidentified cadavers. In the above
      study, autopsied tissue samples without storage or stored in a frozen state were
      used. This study examined JCV DNA sequence modifications caused by formalin
      fixation, in an attempt to elucidate whether formalin-fixed, paraffin-embedded
      tissue samples can also be used to determine the genotypes of JCV DNA in the
      kidney. In four cases, a 610 bp typing region of the JCV genome was PCR-amplified
      from renal tissues stored for 1 year in three different states: frozen at -80
      degrees C [Amaker, B.H., Chandler, F.W., Huey, L.O., Colwell, R.M., 1997.
      Molecular detection of JC virus in embalmed, formalin-fixed, paraffin-embedded
      brain tissue. J. Forensic Sci., 1157-1159], formalin-fixed, paraffin-embedded
      [Ault, G.S., Stoner, G.L., 1992. Two major types of JC virus defined in
      progressive multifocal leukoencephalopathy brain by early and late coding region
      DNA sequences. J. Gen. Virol. 73, 2669-2678], and soaked in 5% formalin [Baksh,
      F.K., Finkelstein, S.D., Swalskey, P.A., Stoner, G.L., Ryschkewitsch, C.F.,
      Randhawa, P.R., 2001. Molecular genotyping of BK and JC virus in human
      polyomavirus-associated interstitial nephritis after renal transplantation. Am.
      J. Kidney Dis. 38 (2), 354-365]. The amplified fragments were cloned, and the
      resultant clones were sequenced. In frozen samples, single sequences ('original'
      sequences) were detected in all cases. In formalin-fixed, paraffin-embedded
      samples, not only the original sequences but also those with 1-6 base
      substitutions were detected. From formalin-soaked samples, the original sequences
      and those with 1-5 and 10-13 substitutions were detected. The genotyping of JCV
      DNA was not hampered by the presence of 1-6 substitutions, but a shift in JCV
      genotypes was observed in sequences with 10-13 substitutions. Thus, it was
      concluded that the genotypes of JCV DNA in the kidney can be determined only with
      specimens stored in a frozen state or formalin-fixed for a short time.

PMID- 15847918
TI  - Determination of poliovirus-specific IgA in saliva by ELISA tests.
AB  - This study describes three ELISA methods for detection of immunoglobulin A (IgA)
      specific to three types of Sabin strains of poliovirus in saliva taken from 70
      children aged 6-7 years vaccinated with a full course of oral poliovirus vaccine
      (OPV). Of the three ELISA methods (conventional IgA ELISA and two new methods
      described in this communication, the alpha-capture ELISA and Inhibition ELISA),
      alpha-capture ELISA demonstrated the highest sensitivity, with all saliva samples
      testing positive for Sabin poliovirus strains specific IgA antibodies of 1-3
      types. Of 62 available alpha-capture ELISA positive saliva samples, all were also
      positive by the inhibition ELISA, and a significant correlation was found between
      the results. Fifty-two available saliva samples were screened by the three ELISA
      tests with positive results, and a significant correlation was found between the
      alpha-capture ELISA and the IgA ELISA; the correlation between the IgA ELISA and
      inhibition ELISA was not significant. The results of this study suggest that
      determination of Sabin poliovirus-specific IgA in human saliva by the ELISA
      techniques (especially by the novel alpha-capture ELISA) can be used reliably for
      evaluation of mucosal immunity in large groups of people immunized with
      poliovirus vaccines and for epidemiological studies.

PMID- 15847919
TI  - Development of three multiplex RT-PCR assays for the detection of 12 respiratory
      RNA viruses.
AB  - Three multiplex hemi-nested RT-PCR assays were developed to detect simultaneously
      12 RNA respiratory viruses: influenza viruses A, B and C, human respiratory
      syncytial virus (hRSV), human metapneumovirus (hMPV), parainfluenza virus types 1
      4 (PIV-1, -2, -3 and -4), human coronavirus OC43 and 229E (HCoV) and rhinovirus
      (hRV). An internal amplification control was included in one of the RT-PCR
      assays. The RT-PCR multiplex 1 and the hemi-nested multiplex 1 detected 1 and 0.1
      TCID50 of RSV A, respectively, and 0.01 and 0.001 TCID50 of influenza virus
      A/H3N2, respectively. Two hundred and three nasal aspirates from hospitalised
      children were retrospectively tested in comparison with two conventional methods:
      direct immunofluorescence assay and viral isolation technique. Almost all samples
      (89/91) that were positive by immunofluorescence assay and/or viral isolation
      technique were detected by the multiplex assay. This method also detected an
      additional 85 viruses and 33 co-infections. The overall sensitivity (98%),
      rapidity and enhanced efficiency of these multiplex hemi-nested RT-PCR assays
      suggest that they would be a significant improvement over conventional methods
      for the detection of a broad spectrum of respiratory viruses.

PMID- 15847920
TI  - Expression and spectroscopic analysis of a mutant hepatitis B virus onco-protein
      HBx without cysteine residues.
AB  - Chronic infection of the hepatitis B virus (HBV) is one of the causes leading to
      liver cancer. The 3.2kb genome of HBV encodes four proteins: core antigen,
      surface antigen, a DNA polymerase and the X protein (HBx). The biological
      functions of HBx are not fully understood. It has been shown that HBx is a potent
      trans-activator, which activates transcription of many cellular and viral
      promoters indirectly via protein-protein interactions. These transactivating
      activities of HBx may contribute to the development of hepatocellular carcinoma.
      In this paper a truncated mini-HBx(-Cys) (18-142) protein, where the cysteines
      had been either deleted or substituted by serines, was constructed by site
      directed mutagenesis and overexpressed as a 6xHis fusion protein in Escherichia
      coli. The 6xHis-mini-HBx(-Cys) protein was isolated from inclusion bodies,
      purified by Ni-affinity chromatography under denaturing conditions and refolded
      by sequential dialysis. The structure of the 6xHis-mini-HBx(-Cys) protein was
      analyzed by circular dichroism, fluorescence and one-dimensional NMR
      spectroscopic assays. The data presented here suggest that HBx is unstructured
      but has a propensity to gain secondary structure under specific experimental
      conditions. Its conformational flexibility might partially explain its functional
      complexity, namely its capacity to interact with a wide array of signaling
      proteins, transcriptional regulators and nucleic acids.

PMID- 15847921
TI  - Evaluation of rapid HIV testing strategies in under equipped laboratories in the
      Central African Republic.
AB  - Voluntary testing is described as being cornerstone to impact the spread of human
      immunodeficiency virus (HIV) infection if the person who tests positive is
      counseled. Therefore, simple, accurate and affordable diagnostic tests are
      required. The immunoblot test used in developed countries is too expensive for
      large-scale use in developing countries. Therefore, alternative strategies must
      be developed. A strategy based on two consecutive rapid tests was tested. This
      strategy used the Determine HIV-1/2 (Abbott Laboratories, Tokyo, Japan) rapid
      immunochromatographic test as a screening test and the Uni-Gold HIV test (Trinity
      Biotech, Dublin, Ireland), SDHO HIV 1/2 test (SDHO laboratories, Saint-Sauveur
      des Monts, Canada), HIV 1/2 Quick test (Cypress Diagnostics, Langdorp, Belgium)
      or Retrocheck HIV test (Qualpro Diagnostics, Goa, India) as a confirmatory test.
      Reference serum samples (HIV-positive and HIV-negative) were first used to
      evaluate the four confirmatory tests. Secondly, 159 serum samples were used to
      compare the "consecutive" testing strategy used in our laboratory with the two
      test strategy. Thirdly, we tested the feasibility of using this two-test strategy
      in a under equipped laboratory. The sensitivity and negative predictive value of
      both test strategies were 100%. The specificity and positive predictive value of
      the four confirmatory tests were similar (>98%). The strategy used in our
      laboratory and the two-test strategy always gave identical results, regardless of
      where this strategy was performed (Institut Pasteur de Bangui or M'baiki
      hospital). This new strategy appears to be reliable, simple, feasible and rapid
      in under equipped laboratories. It allows counseling and results to be given on
      the same day, which should improve post-test counseling.

PMID- 15847922
TI  - Development of a ssRNA internal control template reagent for a multiplex RT-PCR
      to detect turkey astroviruses.
AB  - Turkey astrovirus (TAstV), a positive sense single-stranded RNA (ssRNA) virus, is
      an important causative agent of enteritis of poults. The detection and diagnosis
      of astroviruses have been mainly dependent on electron microscopy (EM). However,
      EM is not very sensitive. Reverse transcription-polymerase chain reaction (RT
      PCR) has high specificity and sensitivity. Thus, monoplex RT-PCR and multiplex RT
      PCR for detection of TAstVs were developed in our laboratory. RT-PCR could be
      adversely affected by many factors, which would result in lowering the
      sensitivity of the reaction. To minimize this pitfall of RT-PCR, a ssRNA internal
      control (IC) template reagent containing two sets of primer sequences (SRV and
      AFCP) specific to the capsid region of TAstV genomes was developed, and applied
      to the multiplex RT-PCR. Sixty-four fecal specimens from 2-week-old poults with
      enteritis were tested using the multiplex RT-PCR with the IC serving as a co
      amplification template. An overall test inhibition rate of 12.5% was found for
      the RT-PCR, which can be used to decrease the false-negative rate. The approach
      to the generation of the IC developed in this study is simple, convenient and
      productive, and can be used as a universal protocol to generate a ssRNA IC
      template reagent for RT-PCR.

PMID- 15847923
TI  - Effects of cold storage on detection of avian infectious bronchitis virus in
      chicken carcasses and local antibodies in tracheal washes.
AB  - In order to test the survivability of infectious bronchitis virus (IBV) in dead
      chicken carcasses during 24 h of cold storage, 7 week-old specific-pathogen-free
      chickens were infected with virulent IBV Massachusetts strain M41, and were
      killed humanely 10 days later. Carcasses were stored in a cold room at 4 degrees
      C. After 1, 3, 6, 9, 12 or 24 h of storage, necropsies were carried out. Trachea,
      lung, kidney and rectum were collected for virus isolation by tracheal organ
      culture (TOC) or embryonated chicken eggs (ECE), and detection by nested reverse
      transcriptase polymerase chain reaction (RT-PCR). IBV was detected by RT-PCR at
      all sampling times, except for 1 and 6 h of storage in kidney and 9 h of storage
      in kidney and rectum. For ECE, isolation was obtained at all sampling points,
      except at 1 and 24 h of storage in lungs. Isolation by tracheal organ cultures
      was less successful, except from rectum. In addition to sampling for virus,
      tracheal washes were collected from each carcass to measure the ability to detect
      local antibodies after storage. Levels of IgA in tracheal washes remained high
      for up to 9 h of storage, suggesting that accurate sampling for research purposes
      when required must be carried out within this time.

PMID- 15847924
TI  - Phenotypic and genotypic characteristics of new euploid-diploid lymphoblastoid B
      cell lines EBV+, normal human bone marrow derived, spontaneously overgrown in
      vitro.
AB  - The present study describes the phenotypic and genotypic features of seven
      individual growth transformed, euploid-diploid EBV+ human B cell lines arisen
      spontaneously in vitro. The lines, obtained under general and standard culture
      conditions (un-manipulated), from seven individual bone marrow samples of 18
      healthy young adults, Caucasian, of both sexes, display many traits of normal B
      cells and represent a mixture of EBV infected latently (latency type III) and
      producer cells (5-16% VCA+ by immunofluorescence) releasing seven individual
      different viral strains [Fruscalzo et al., 2001. DNA sequence heterogeneity
      within the Epstein-Barr virus family of repeats in the latent origin of
      replication. Gene 265, 165-173] similar to the B95-8 genotype as shown by results
      of Southern blot of BamHI-digested DNA fragment. These tests were planned to
      characterize more fully this panel of new bone marrow cell lines sharing normal B
      cell traits.

PMID- 15847925
TI  - Generic RT-nested-PCR for detection of flaviviruses using degenerated primers and
      internal control followed by sequencing for specific identification.
AB  - Flaviviruses are a widespread and numerous group of arboviruses that can cause
      serious illness in humans. The continuous and slow spread of certain
      flaviviruses, such as Dengue viruses, and the recent entry and spread of West
      Nile virus to the American continent, point to the need to control these
      infections. This control requires the use of suitable techniques for diagnostic
      and surveillance programmes. A generic RT-nested-PCR that is, theoretically, able
      to detect each member of the group has been designed. The identification of the
      detected virus is carried out by sequencing. The introduction of an internal
      control would reduce the number of false negative results and could be used to
      quantify the viral load in clinical samples where the method works well.

PMID- 15847926
TI  - Novel single-round PCR and cloning of full-length envelope genes of HIV-1 may
      yield new insight into biomolecular antibacterial drug development.
AB  - Nested or semi-nested polymerase chain reaction (PCR) with a 'hot start' is the
      preferred amplification method for full-length, in-frame envelope genes (gp160)
      of the human immunodeficiency virus type 1 (HIV-1). This generally follows an
      extensive screening process. This paper describes an effective single-round PCR
      method and cloning process for HIV-1 gp160 from clinical samples, and cell and
      tissue cultures developed during the early stages of construction of a molecular
      HIV-1 vaccine. The amplification method and cloning process are adaptable to full
      length HIV-1, HIV-2, and other viral production processes. Also described within,
      is one solution to the most-often extensive screening process for inserts
      containing full-length, in-frame gp160. Of note, was a perceived toxicity of
      gp160 to bacteria during the culturing and the scaling-up process that created
      the extensive screening process. The toxicity association was not found with the
      individual gp160 genes, the gp120 or the gp41 gene, with other viral regions
      similar or larger in molecular weight to gp160, or with other non-gp160 full
      length genes of HIV-1 such as pol and gag genes. The HIV-1 gp160 toxicity issue
      may provide insight towards the development of the next generation of novel
      biomolecular drugs against bacterial infections.

PMID- 15847927
TI  - Detection of West Nile virus and Japanese encephalitis virus using real-time PCR
      with a probe common to both viruses.
AB  - A diagnostic method to distinguish between West Nile virus (WNV) and Japanese
      encephalitis virus (JEV) based on fluorogenic real-time polymerase chain reaction
      (TaqMan) assays was developed. To detect WNV and JEV with a single probe, a probe
      was designed to correspond to sequences in the core protein region that are
      shared by both viruses. The specificity of this assay depended on the primer sets
      used, which were specific to the target virus sequences: the primer set for WNV
      could detect only WNV strains and the primer set for JEV could detect only JEV
      strains. The assays were tested by detection of viruses from experimentally
      infected animal tissues. The method described in this study will be useful for
      the simultaneous discrimination of WNV and JEV in areas where JEV is endemic,
      such as East Asia.

PMID- 15847928
TI  - Environmental surveillance of wild poliovirus circulation in Egypt--balancing
      between detection sensitivity and workload.
AB  - Examination of sewage specimens for poliovirus (environmental surveillance) was
      adopted as a supplementary tool in the surveillance of poliomyelitis in Egypt.
      Sewage samples were concentrated about 50-fold using a simple two-phase
      separation technique, and inoculated in cell cultures in two collaborating
      laboratories in parallel. All but 9 of the 293 (97%) samples collected from
      January 2001 to December 2002 contained poliovirus and/or other enteroviruses,
      with polioviruses being detected in 84% of the samples. The proportion of
      specimens containing type 1 wild poliovirus (PV1W, the North-East African (NEAF)
      genotype) was less in 2002 (16%) than in 2001 (57%), and further decreased in
      2003. While the overall sensitivity to detect PV1W was similar in the two
      collaborating laboratories, the specimens scored positive were not identical.
      Parallel cultures inoculated with aliquots of a given specimen very frequently
      resulted in isolation of different viruses. Moreover, partial sequence analysis
      occasionally revealed representatives of different genetic lineages of PV1W in a
      given specimen. These results emphasize the need to use intensive laboratory
      analysis to optimise sample sensitivity in environmental poliovirus surveillance,
      and the difficulties in reproducing the isolation results by simple re
      inoculation of samples containing a mixture of different viruses.

PMID- 15847929
TI  - Adenovirus detection in shellfish and urban sewage in Morocco (Casablanca region)
      by the polymerase chain reaction.
AB  - Human enteric viruses are largely excreted in faeces. These resistance of these
      viruses in the environment makes their faecal-oral transmission easier. Filter
      feeder organisms such as the mussels are bio-accumulators of viruses
      contaminating their aquatic environment. Thus, undercooked shellfish consumption
      involves sanitary risks. Thirty samples of mussels (Mytilus sp.), were tested,
      half were from an aquaculture origin, the others were from an area more exposed
      to faecal pollution. Fifteen sewage samples from this last area were also
      examined. Viruses were extracted from the digestive tissue by direct elution
      method in a glycine/NaCl pH 9.5 buffer followed by PEG 8000 precipitation. The
      PEG pellets were used for DNA extraction by proteinase K and phenol/chloroform.
      The molecular characterization, by PCR using specific adenovirus primers revealed
      that shellfish growing on Mohammedia (a town in the Casablanca outskirts)
      littoral are contaminated whereas those chosen from aquaculture and bought in the
      central market were not contaminated.

PMID- 15847930
TI  - A refined long RT-PCR technique to amplify complete viral RNA genome sequences
      from clinical samples: application to a novel hepatitis C virus variant of
      genotype 6.
AB  - The goal of this study was to adapt a long RT-PCR technique to amplify large PCR
      fragments from the genome of hepatitis C virus (HCV) isolates using clinical
      samples. This was done by using a reverse transcriptase devoid of RNase H
      activity and a mixture of two antibody-bound thermostable polymerases to combine
      the high processivity of Taq and the high fidelity of Pwo with its 3'-->5'
      exonuclease activity. Other modifications included gentle handling during RNA
      extraction, the absence of tRNA and random primers, a two-step reverse
      transcription procedure to optimize cDNA synthesis, and increasing the annealing
      temperature for primers. With this approach, the HCV-1 genome (nucleotides 35
      9282) was amplified consistently as two overlapping fragments of 5344 and 4675 bp
      from a pooled chimpanzee plasma sample containing approximately 10(6) genome
      copies of HCV RNA/ml. Using the conditions that we identified, 96% of the
      complete genomic sequence of a distinct HCV genotype 6 variant (km45) was
      determined from less than 300 microl of serum. This method should prove useful
      for molecular, epidemiological and clinical studies of hepatitis C where samples
      are limited but complete virus sequence is required, for example, identifying
      mutational hot spots of HCV under specific clinical conditions.

PMID- 15847931
TI  - Assessment of mumps virus growth on various continuous cell lines by virological,
      immunological, molecular and morphological investigations.
AB  - Vero cells have been used as a convenient laboratory substrate for the isolation
      of mumps virus but may not be very sensitive and may select for particular
      adapted variants from clinical specimens. Continuous cell lines were evaluated
      for their ability to support the replication of mumps virus. Criteria included
      the production of infectious virus, detection of intracellular mumps proteins by
      immunofluorescence and electron microscopy and detection of specific nucleic acid
      by RT-PCR. Of the cells tested, CaCo-2, PLC/PRF/5, and Vero cells produced
      infectious virus, with Vero and CaCo-2 being the most permissive. The other
      substrates tested included cells of murine, canine and human origin showed signs
      of intracellular proteins and RNA but the amounts produced were much lower, and
      no infectious virus was detected in some cases. The virus use was a low passage
      of a Vero derived wild type strain, and it will ultimately be necessary to
      continue the studies with an unpassaged clinical specimen to identify a cell line
      able to isolate mumps virus at high efficiency and in unmodified form.

PMID- 15847932
TI  - Use of armored RNA as a standard to construct a calibration curve for real-time
      RT-PCR.
AB  - Armored Enterovirus RNA was used to standardize a real-time reverse transcription
      (RT)-PCR for environmental testing. Armored technology is a system to produce a
      robust and stable RNA standard, trapped into phage proteins, to be used as
      internal control. The Armored Enterovirus RNA protected sequence includes 263 bp
      of highly conserved sequences in 5' UTR region. During these tests, Armored RNA
      has been used to produce a calibration curve, comparing three different
      fluorogenic chemistry: TaqMan system, Syber Green I and Lux-primers. The
      effective evaluation of three amplifying commercial reagent kits, in use to carry
      out real-time RT-PCR, and several extraction procedures of protected viral RNA
      have been carried out. The highest Armored RNA recovery was obtained by heat
      treatment while chemical extraction may decrease the quantity of RNA. The best
      sensitivity and specificity was obtained using the Syber Green I technique since
      it is a reproducible test, easy to use and the cheapest one. TaqMan and Lux
      primer assays provide good RT-PCR efficiency in relationship to the several
      extraction methods used, since labelled probe or primer request in these
      chemistry strategies, increases the cost of testing.

PMID- 15847933
TI  - Complete nucleotide sequences of two RNA segments of human picobirnavirus.
AB  - Picobirnaviruses are unclassified, non-enveloped, spherical, small viruses with a
      genome comprising two double-stranded RNA segments. Only incomplete sequence data
      on picobirnaviruses are available so far. By cloning involving single primer
      amplification, full-length cDNAs were prepared corresponding to RNA segments 1
      and 2 of a picobirnavirus (strain Hy005102) isolated from a stool specimen from
      an infant with acute non-bacterial gastroenteritis in Thailand, and the complete
      nucleotide sequences were determined. RNA segments 1 and 2 are 2,525 and 1,745
      base pairs in length, respectively. RNA segment 1 encodes two open reading frames
      (ORFs) of 224 and 552 amino acids, and RNA segment 2 codes for a single ORF of
      534 amino acids. On comparison with a part of the nucleotide sequences of the RNA
      segment, 2 of the other published picobirnavirus strains, the Thai strain was
      found to be related most closely to one of the US strains.

PMID- 15847934
TI  - Study on the resistance of severe acute respiratory syndrome-associated
      coronavirus.
AB  - In this study, the persistence of severe acute respiratory syndrome-associated
      coronavirus (SARS-CoV) was observed in feces, urine and water. In addition, the
      inactivation of SARS-CoV in wastewater with sodium hypochlorite and chlorine
      dioxide was also studied. In vitro experiments demonstrated that the virus could
      only persist for 2 days in hospital wastewater, domestic sewage and dechlorinated
      tap water, while 3 days in feces, 14 days in PBS and 17 days in urine at 20
      degrees C. However, at 4 degrees C, the SARS-CoV could persist for 14 days in
      wastewater and at least 17 days in feces or urine. SARS-CoV is more susceptible
      to disinfectants than Escherichia coli and f2 phage. Free chlorine was found to
      inactivate SARS-CoV better than chlorine dioxide. Free residue chlorine over 0.5
      mg/L for chlorine or 2.19 mg/L for chlorine dioxide in wastewater ensures
      complete inactivation of SARS-CoV while it does not inactivate completely E. coli
      and f2 phage.

PMID- 15847935
TI  - Canine parvovirus infection: which diagnostic test for virus?
AB  - Five laboratory tests for diagnosis of canine parvovirus type 2 (CPV-2) infection
      were employed to test 89 faecal samples collected from dogs with diarrhoea. The
      tests analysed were immunochromatography (IC), haemagglutination (HA), virus
      isolation (VI), conventional and real-time PCR. IC, HA, VI and conventional or
      real-time PCR were able, respectively, to detect CPV-2 antigen or nucleic acid in
      41, 50, 54, 68 and 73 of the samples. The best correlation was found between
      conventional and real-time PCR, with an overall agreement of 94.38%. Sixty-eight
      samples that tested positive by HA, VI or conventional PCR were subjected to
      antigenic and/or genetic analyses of the CPV-2 strains by monoclonal antibody
      (MAb), restriction fragment-length polymorphism (RFLP) and/or sequence analyses.
      In sum, out of the 68 strains analysed, 26 were characterised as CPV-2a, 18 as
      CPV-2b and 24 as a CPV-2 Glu-426 mutant recently identified in Italy.

PMID- 15847936
TI  - Detection of vaccinia virus DNA on the LightCycler by fluorescence melting curve
      analysis.
AB  - After eradication of variola virus the worldwide vaccination program was stopped
      to avoid the severe complications observed in a small fraction of vaccinees.
      Hence, there is at least one non-vaccinated generation in the human population
      that is immunologically naive with respect to variola virus infections. The
      possibility of a deliberate release of variola virus by bioterrorist attacks has
      led to the resumption of vaccination of hospital employees and military personnel
      with vaccinia virus in certain parts of the world. However, the appearance of a
      single confirmed smallpox case worldwide would result in vaccination of possible
      contact persons with vaccinia virus. Therefore, reliable confirmation of vaccinia
      virus in patients presenting with smallpox-like syndromes is required. A vaccinia
      virus-specific single nucleotide polymorphism was identified in the gene B8R
      coding for a vaccinia virus IFNgamma receptor. Based on this polymorphism, the
      LightCycler real-time PCR assay detects vaccinia virus DNA in a linear range from
      10(6) to 10 genome equivalents and discriminates vaccinia virus from other
      orthopoxviruses by fluorescence melting curve analysis (DeltaT = 9 degrees C).
      While the assay amplifies generically DNA of all orthopoxviruses tested,
      amplification curves are only displayed for vaccinia virus strains including
      strains formerly used for vaccination. In addition, an internal amplification
      control is described that allows reliable interpretation of results.

PMID- 15847937
TI  - DNA recovery from Hybrid Capture II samples stored in specimen transport medium
      with denaturing reagent, for the detection of human papillomavirus by PCR.
AB  - The purpose of this study was to examine the quality of DNA recovered for human
      papillomavirus (HPV) detection using polymerase chain reaction (PCR) in samples
      that had been collected for Hybrid Capture II (HCII), testing and stored in
      specimen transport medium (STM) with denaturing reagent at -20 degrees C for 18
      months. Endocervical tissue was collected from 92 women for HCII assay using the
      Digene STM, and a Papanicolaou smear was carried out in all cases. Seven women
      had normal colposcopy results. The remaining 85 patients underwent colposcopy
      directed biopsy or cervical conization for histological investigation. Of the 92
      samples tested, 84 were HCII-positive and 8 were negative. Quality control for
      amplification was carried out with beta-globin primers G73 and G74, and HPV was
      tested using PGMY09 and PGMY11. DNA was recovered from 83 of the 92 samples
      (90%). Among the 84 samples HCII-positive initially, HPV was detected by PCR in
      56 (67%). PCR did not detect HPV DNA in the eight samples that were HCII
      negative, although five of them were positive for beta-globin. This paper
      describes a novel DNA extraction technique that may permit exact HPV typing in
      stored samples collected originally for HCII testing, making it possible to carry
      out retrospective investigations to retrieve information on specific HPV types in
      large HCII series.

PMID- 15847938
TI  - Detection and typing of herpes simplex DNA in genital swabs by real-time
      polymerase chain reaction.
AB  - The LightCycler polymerase chain reaction (PCR) is a sensitive assay for the
      detection of Herpes simplex virus (HSV) DNA in muco-cutaneous swabs. Software
      based analysis of the probe melting temperature (Tm) can be used to discriminate
      between HSV types (HSV-1 and HSV-2). Among 76 HSV DNA positive genital swabs,
      atypical Tms were observed in 14 (18%). The 14 samples were all typed as HSV-2 by
      sequence alignment. In 4/14 samples, the atypical Tm was associated with sequence
      variation at the probe-binding site. Among 10 samples with conserved sequences,
      Tms were influenced by the specimen preparation method prior to PCR. These
      findings indicate that multiple factors including, but not limited to sequence
      variation complicate melting curve analysis following real-time PCR. Alternative
      typing methods are recommended for specimens with atypical melting curves.

PMID- 15847939
TI  - Real-time PCR quantitation of hepatitis B virus DNA using automated sample
      preparation and murine cytomegalovirus internal control.
AB  - Quantitation of circulating hepatitis B virus (HBV) DNA is important for
      monitoring disease progression and for assessing the response to antiviral
      therapy. Several commercial and 'in house' assays for HBV DNA quantitation have
      been described but many of these have limitations of relatively low sensitivity
      and limited dynamic range. This study describes the development and evaluation of
      a FRET-based real-time PCR assay designed to overcome these limitations and to
      provide accurate quantitation of DNA from all eight genotypes of HBV (A-H). The
      assay employs a fully automated nucleic acid extraction system permitting high
      sample throughput with minimal 'hands-on' time and incorporates a murine
      cytomegalovirus (mCMV) internal control to prevent false negative results and
      under-reporting due to unrecognised problems with viral lysis, DNA purification
      or PCR amplification. Sensitivity, assessed by Probit analysis at the 95%
      detection level, was 24.4 IU/ml, associated with an extremely wide dynamic range
      (approximately 9 log10). Coefficients of variation were low for both intra-assay
      and inter-assay variability (CV%, 7-11%) and quantitative data correlated well
      (R2 = 0.97) with the Digene hybrid capture assay. This assay provides an ideal
      system for therapeutic monitoring and for studying the relationship between HBV
      viral load and stage of disease.

PMID- 15847940
TI  - Semi-nested PCR for detection and typing of bovine Papillomavirus type 2 in
      urinary bladder and whole blood from cattle with enzootic haematuria.
AB  - Bovine Papillomavirus type 2 (BPV-2) and chronic intoxication by bracken fern
      ingestion were associated with urinary bladder lesions and the clinical signs of
      enzootic haematuria in adult cattle. Clinically enzootic haematuria is
      characterized by intermittent haematuria followed by animal death. Enzootic
      haematuria causes considerable economical impact on extensive cattle breeding
      worldwide. The demonstration of BPV-2 participation in the etiology of bovine
      urinary bladder carcinoma by conventional virological methods is not easy and the
      integrity of epidemiological studies relies on methods that are sensitive and
      specific for BPV-2 detection and typing. A multiplex-PCR was evaluated for BPV-2
      L1 gene and bovine mitochondrial genome ND5 gene (internal control) detection
      followed by a second round of BPV-2 amplification by a semi-nested PCR (SN-PCR).
      Six skin papilloma samples were used for PCR technique development. Twenty-two
      urinary bladder samples from symptomatic (n = 12) and asymptomatic (n = 10,
      control group) cows and 25 blood samples from cows grazed on enzootic haematuria
      endemic (n = 14) and enzootic haematuria-free (n = 11, control group)
      geographical regions of Parana State, Brazil were analyzed. The SN-PCR detected
      BPV-2 in seven urinary bladder and 10 whole blood samples collected from cows
      with enzootic haematuria and in one urinary bladder and one whole blood samples
      of asymptomatic cows. The specificity of the amplicon was performed by
      restriction fragment length polymorphism and sequence analysis. The SN-PCR
      technique developed in this study will make possible the realization of diagnosis
      and comparative epidemiological studies to evaluate BPV-2 infection rates in
      cattle, and the association of this infection with bracken fern chronic
      intoxication in the etiology of enzootic haematuria and opens the possibility of
      ante mortem studies by lymphocytes analysis.

PMID- 15847941
TI  - Morphological recovery in the reattached retina of the toad Bufo marinus: a new
      experimental model of retinal detachment.
AB  - BACKGROUND: The retinal pigment epithelium (RPE) of the toad (Bufo marinus) has
      been used in many studies as a model for understanding its role and interaction
      with the neural retina. The toad's retina has been used to establish a new in
      vitro model of experimental retinal detachment (RD) and replacement . It has been
      shown that the electrophysiological measures of retinal function recovered
      following complete RD. The toad was chosen because its RPE is similar to the
      mammalian RPE . In this report, light microscopy was used to characterize the
      morphologic changes that occur in the RPE and neural retina following
      RD/replacement and to correlate these findings with recovery of
      electrophysiologic function. METHODS: Retinas from Bufo marinus were studied in
      vitro. The neural retina completely detached from the RPE and then replaced. At
      various times after replacement, neural retina-RPE tissues were processed for
      light microscopy. RESULTS: At 30 min after replacement, the subretinal space was
      greatly expanded, and the apical processes that normally ensheath the rod outer
      segments were short and no longer contacted the rod outer segments. The RPE was
      swollen, contained many vacuoles and the apical surface was rounded. By 2 h after
      replacement, the subretinal space was significantly resorbed and contained many
      shredded rod outer segments; RPE cells were still swollen, although less. During
      the next 5-10 h, the number of phagosomes in the RPE cytoplasm increased and the
      number of shredded rod outer segments in the subretinal space decreased. RPE
      cells regained their normal size and interdigitation of apical processes and rod
      outer segments were observed. CONCLUSIONS: These results demonstrate the re
      establishment of morphological interactions between the RPE and neural retina
      within hours following RD/replacement. Morphological recovery coincides with
      recovery of electrophysiologic parameters. This is a good model to investigate
      the retinal pigment epithelium (RPE) and neural retina mechanisms involved in
      retinal adhesion and recovery from retinal detachment.

PMID- 15847942
TI  - In vitro and in vivo study of octacosanol metabolism.
AB  - BACKGROUND: Policosanol is a mixture of very-long-chain aliphatic alcohols
      purified from sugar cane wax with cholesterol-lowering effects, whose main
      component is octacosanol. Scarce data about the metabolism of octacosanol and the
      other fatty alcohols composing policosanol have been published. METHODS: Human
      fibroblasts were cultured in presence of (3)H-octacosanol during 0.5, 2 and 4 h.
      Lipid extracts were analyzed by thin layer chromatography, and the spots
      corresponding to octacosanol and octacosanoic acid were identified comparing with
      authentic standards. Spots were scraped, transferred to vials and radioactivity
      was measured. For corroborating the presence of octacosanol and octacosanoic
      acid, samples were analyzed by gas chromatography-mass spectrometry (GC-MS). The
      in vivo study of octacosanol metabolism was conducted in rats and Macaca
      arctoides monkeys. Rats were orally administered with policosanol (60 mg/kg) and
      free octacosanol and octacosanoic acid were identified in liver and plasma by GC
      MS at various time intervals. Monkeys were orally and endovenously treated with
      policosanol (10 mg/kg) and the presence of free octacosanol, octacosanoic acid
      and some chain-shortened FA was investigated. RESULTS: When fibroblasts were
      cultured in presence of (3)H-octacosanol, three spots were found: a first one
      corresponded to octacosanoic acid, a second to octacosanol and a third one
      remained unidentified. The radioactivity on the spot of octacosanoic acid
      slightly decreased throughout the incubation but increased in the third spot.
      Octacosanol and free octacosanoic acids were also identified in plasma of monkeys
      orally administered with policosanol. In addition, plasma samples showed free
      saturated acids, palmitic acid being the most abundant, followed by oleic and
      mystiric acids. Unsaturated acids (oleic and palmitoleic) were also observed.
      CONCLUSIONS: The present study demonstrates that octacosanoic acid is formed
      after incubation of fibroblast cultures with (3)H-octacosanol and after oral
      dosing with policosanol to rats. In addition, we demonstrated that shortened
      saturated (myristic, palmitic and stearic) and unsaturated (oleic, palmitoleic)
      FA are also formed after oral dosing with policosanol to monkeys. The present
      results are consistent with the fact that octacosanol metabolism is linked to FA
      metabolism via beta-oxidation, but further studies need to explore the occurrence
      of more metabolites proving such hypothesis.

PMID- 15847943
TI  - Lack of effect of extremely low frequency electromagnetic fields on cyclin
      dependent kinase 4 inhibitor gene p18(INK4C) in electric energy workers.
AB  - BACKGROUND: Long-term exposure to extremely low frequency magnetic fields (ELF
      MFs) may be a risk factor for human cancer. One mechanism through which ELF-MFs
      could influence neoplastic development is the deletion/mutation of cancer-related
      genes. Cellular proliferation follows an orderly progression through the cell
      cycle, which is governed by different cyclins and cyclin-dependent kinase
      inhibitors (CDKIs). The putative tumor suppressor gene p18(INK4C) encodes a
      specific inhibitor of cyclin D-cyclin-dependent kinase 4 inhibitor complexes
      having an important role in cell-cyclin regulation. It has been found to be
      deleted/mutated in a variety of human cancers. Therefore, this study is to
      investigate whether or not long-term extremely low frequency electromagnetic
      field exposure may be a risk factor for human cancer due to the gene p18(INK4C)
      deletion/mutation. METHODS: The study was carried out on 31 male electric workers
      and 30 healthy males between 30 and 40 years of age from the same geographic area
      and with similar lifestyles. We studied both groups by polymerase chain reaction
      single strand conformation polymorphism (PCR-SSCP). RESULTS: In comparison to the
      controls, band migration of exon 1 was found to be indifferent in all the
      subjects tested. However, only exon 2 of two electric workers was slow in
      migration with respect to both control and other subjects in the same class. This
      slow migration suggests that point mutations or polymorphisms may exist in this
      region of the p18(INK4C) gene. The relative risk (RR) for the unmatched analysis
      was 1,069 (95% confidence interval [CI] 0.975-1.172). CONCLUSIONS: The results
      suggest that long-term ELF-MFs exposure does not significantly increase the risk
      of cancer.

PMID- 15847944
TI  - Thrombopoietin and interleukin-6 in children with pneumonia-associated
      thrombocytosis.
AB  - BACKGROUND: The aim of this study was to investigate why some, but not all,
      children develop thrombocytosis during the course of pneumonia. METHODS: The
      retrospective study included 40 healthy children and 75 children with pneumonia:
      17 patients with platelet count within the reference values, i.e., platelet count
      </=450 x 10(9)/L, and 58 with thrombocytosis >450 x 10(9)/L. Erythrocyte
      sedimentation rate, leukocyte and platelet counts, and concentrations of
      hemoglobin, C-reactive protein, interleukin-6 and thrombopoietin were determined
      in the blood of patients and control groups of children. RESULTS: Patients with
      thrombocytosis were slightly younger (3.0 +/- 1.8 years and median 2.5 years,
      respectively) than patients with normal platelet count (3.8 +/- 2.4 years and
      median 4 years, respectively). Additionally, according to clinical and
      radiological findings, pneumonia in children with thrombocytosis had a more
      severe and protracted course. Serum thrombopoietin concentrations were found to
      be 91.2 +/- 41.7 ng/L (range: 14.3-166.7 ng/L) in patients with normal platelet
      count (313 +/- 70 x 10(9)/L, range: 206-428 x 10(9)/L). In patients with
      thrombocytosis (581 +/- 131 x 10(9)/L, range: 450-830 x 10(9)/L) serum
      thrombopoietin ranged from 63.6 to 1115.9 ng/L (526.6 +/- 268.4 ng/L). In these
      patients both concentration of hemoglobin (114 +/- 12 g/L) and iron (4.3 +/- 1.3
      micromol/L) significantly decreased as compared with the control group.
      CONCLUSIONS: Study results suggested the possible development of reactive
      thrombocytosis in children with pneumonia. As platelets are involved in
      inflammatory reaction, reactive thrombocytosis might be part of the mechanism of
      defense. Reactive thrombocytosis may develop as a sequel of either anemia or
      inflammatory reaction (or both).

PMID- 15847945
TI  - Multimodal treatment of locally advanced cervical cancer.
AB  - BACKGROUND: Radiation therapy with concomitant chemotherapy is the standard
      treatment for locally advanced cervical cancer. In Mexico, most patients are
      still treated with radiation therapy alone. The aim of this work was to
      demonstrate that results obtained with combined treatments in the Mexican
      population are similar to those reported in the literature. METHODS: Survival was
      analyzed in three sequential phase II studies of combined treatment: neoadjuvant
      chemotherapy followed by surgery (NEOCT+Sx) -February to July 1999; concomitant
      chemoradiotherapy (CT/RT) -August to December 1999; and neoadjuvant chemotherapy
      followed by surgery plus adjuvant chemoradiotherapy (NEOCT+Sx+CT/RT) -December
      2000 to June 2001. These results were compared with a historical control group
      treated with radiation therapy alone between September and December 1998. The
      Kaplan-Meier product-limit method, log-rank test and Cox proportional hazards
      model were used for analysis. RESULTS: Results showed that the three combined
      modalities significantly reduced the risk of death. Treatment with NEOCT+Sx
      reduced the risk to 0.452 (95% CI 0.246-0.830), p=0.010. The risk reduction with
      CT/RT was 0.408 (95% CI 0.218-0.762), p=0.005, and for the group of patients
      receiving NEOCT+Sx+CT/RT risk was reduced to 0.365 (95% CI 0.169-0.787), p=0.010.
      The corresponding absolute survival benefit was 14% for patients in stages IB2
      IIA, 24% for IIB, and 21% for stage IIIB. CONCLUSIONS: Within the limitations of
      a non-randomized study, our results are in agreement with those obtained from
      published randomized phase III trials which state that radiation therapy alone is
      a suboptimal treatment for locally advanced cervical cancer; hence, patients
      should receive cisplatin-based chemoradiotherapy as a standard treatment.

PMID- 15847946
TI  - The impact of co-morbid conditions on the SF-36: a primary-care-based study among
      hypertensives.
AB  - BACKGROUND: Comorbidities in hypertension complicate the course causing more
      symptoms and deterioration in a patient's daily life. The aim of this present
      study is to describe the effect of comorbid conditions on health-related quality
      of life (HRQL) in hypertensive patients. METHODS: The study was carried out in
      four different regions of Turkey by 156 general practitioners between October
      1999 and April 2000. In addition to cardiological evaluation, SF-36 health survey
      questionnaire was used for quality of life measurement. Diagnosis of comorbid
      conditions were anamnesis based. RESULTS: The mean age of the group (n=938) was
      58.1 +/- 11.2, and 58.6% (n=550) of the group was female. Total scores of the
      eight domains of SF-36 were lower than the normal population scores. Age and
      gender affected every domain of SF-36 scale negatively. Heart failure affected
      four of the domains, primarily physical domains. Previous transient ischemic
      attack was responsible for low HRQL in emotional role difficulties, vitality, and
      mental health, but previous stroke had an impact on physical functioning and
      emotional role. Previous myocardial infarction affected emotional role
      difficulties negatively whereas previous CABG surgery had a positive impact on
      the same domain. Obesity and angina pectoris affected physical functioning
      negatively, whereas peripheral arterial disease caused low general health
      perception. Nephropathy, retinopathy and diabetes had no impact on HRQL in
      hypertension. CONCLUSIONS: When the contribution of comorbid conditions is taken
      into consideration, it can be noticed that the impact of every other condition is
      similar to the same condition when it is pure. Hypertension per se seems to cause
      less impairment than expected in HRQL.

PMID- 15847947
TI  - Evaluation of iron overload in healthy adult residents of Mexico City.
AB  - BACKGROUND: We described the effects of age, gender and body mass index (BMI) on
      the prevalence of iron overload (IO) in blood donors from Mexico City. METHODS: A
      cross-sectional study of clinically healthy adults was performed. We evaluated
      serum ferritin (SF) concentration to allow us to establish groups with normal
      iron stores (SF >30 microg/L) and with IO (SF >200 microg/L and >300 microg/L for
      women and men), in the following ages groups: 18-29 years, 30-49 years, and 50-64
      years, divided by gender. RESULTS: The study included 1757 subjects. Prevalence
      of IO was 12% in men and 4.8% in women, and prevalence increased in parallel with
      increasing age (15.6, 25.0 and 29.9% and 3.5, 5.2 and 9.6%, for men and women,
      respectively). Regression analysis showed that in men there was a significant
      association of SF and IO with age, BMI and recent blood donation (p <0.01). In
      women, no differences were seen for BMI and recent blood donation. CONCLUSIONS:
      IO is highly prevalent in blood donors residing in Mexico City, more so in men
      than in women. Age, gender and BMI had a positive association with iron stores.
      This report is the initial contribution towards the study of IO in the Mexican
      population.

PMID- 15847948
TI  - Impaired synthesis is not the reason for decreased activity of extracellular
      superoxide dismutase in patients with diabetes.
AB  - BACKGROUND: The aim of the study was to find the cause of decreased activity of
      extracellular superoxide dismutase (EC SOD) in patients with diabetes-is it the
      decreased synthesis or increased glycation? METHODS: Total EC SOD activity, the
      activity of its fractions (A, B, and C) and its glycated form were determined in
      basal state and 30 min after intravenous (i.v.) administration of 50 mg of
      heparin. Patients were given i.v. heparin at a dose of 10,000 IU (100 mg) each 6
      h for at least 3 days, and the activity of EC SOD was determined before the first
      heparin administration, just before each subsequent administration, and 30 min
      after heparin administration. RESULTS: Pre- and postheparinic activities of EC
      SOD and its fraction C in the group of patients with diabetes were significantly
      lower (p <0.001) than in control group. Preheparinic activities of EC SOD did not
      differ between the examined groups of patients. The postheparinic activities were
      different during the first 18 h of treatment. They were significantly lower in
      the group of patients with diabetes. During the following hours, after
      subsequently administered doses, there were no differences in the activity of EC
      SOD between the examined groups. Decline of EC SOD activity was observed after
      administration of repeated doses of heparin both in the examined and in the
      control groups. CONCLUSIONS: The decrease of extracellular superoxide dismutase
      activity in diabetes develops due to excessive glycation but not due to impaired
      synthesis. Therefore, appropriate glycemic control can lead to normalization of
      EC SOD activity.

PMID- 15847949
TI  - Role of glucocorticoids in ototopical antibiotic-steroid preparations in the
      treatment of chronic suppurative otitis media.
AB  - BACKGROUND: It is conventional to use antibiotic-steroid combination eardrops,
      although the advantage of steroid combination has not been substantiated. The
      present prospective randomized comparative study is designed to assess the role
      of glucocorticoids in ototopical antibiotic-steroid preparations in the treatment
      of chronic suppurative otitis media (CSOM). METHODS: Pre-treatment clinical
      assessment, bacteriology of the middle ear discharge and pure tone audiogram were
      done. CSOM with organisms sensitive to gentamicin were treated either with plain
      gentamycin (GM) or gentamycin steroid combination (GM-S) eardrops for a period of
      3 weeks. Post-treatment clinical, bacteriological and audiogram response was
      recorded 1 week after discontinuing the eardrops. The post-treatment clinical
      improvement, bacteriologic improvement and changes in hearing threshold at speech
      frequencies were analyzed by using unpaired Student's t test and chi(2) tests.
      RESULTS: The most common organism associated with CSOM was Pseudomonas aeruginosa
      (33.92%). Clinical improvement was seen in 87.7 and 86.5% cases but
      bacteriological improvement in only 82.5 and 75% of cases treated with GM and GM
      S (p >0.05), respectively. On comparing the pre- and post-treatment pure tone
      audiograms in 95 patients, 28.9% treated with GM and 30% with GM-S showed
      deterioration in bone conduction threshold above 5 dB (p >0.05) at speech
      frequencies. The mean increase in bone conduction in the two groups was 7.7 and
      8.57 dB (p >0.05), respectively. CONCLUSIONS: Our results indicate that there is
      no difference in the clinical and bacteriological improvement or ototoxicity
      either with topical GM or GM-S. Hence, we conclude that it is unnecessary to
      combine steroids with topical antibiotic preparations for the management of CSOM.

PMID- 15847950
TI  - Comparison of fluoxetine and paroxetine in type II diabetes mellitus patients.
AB  - BACKGROUND: This study aims to investigate the efficacy of fluoxetine and
      paroxetine on the levels of depression-anxiety, quality of life, disability, and
      metabolic control in type II diabetes mellitus (DM) patients. METHODS: The
      patients were first applied the Hospital Anxiety-Depression Scale (HADS). After a
      psychiatric interview with patients who had scores above the cut-off point, those
      who were diagnosed as having a major depressive disorder according to DSM-IV
      criteria were applied the Hamilton Depression Rating Scale (HDRS) and the
      Hamilton Anxiety Rating Scale (HARS). Twenty three patients who scored 16 or
      above on the HDRS were included in the study and given the Short Form-36 (SF-36),
      and the Brief Disability Questionnaire (BDQ) and HbA1c levels were measured.
      Patients were randomized on 20 mg/day fluoxetine or 20 mg/day paroxetine
      treatment. The patients were evaluated with the same scales at the 2(nd), 4(th),
      6(th), and the 12(th) weeks. RESULTS: Both groups showed a statistically
      significant decrease in HDRS, HARS, and BDQ scores with comparison to the index
      assessment. At the end of treatment, though not statistically significant, a
      decrease was observed in HbA1c values of the fluoxetine-administered group.
      CONCLUSIONS: Fluoxetine and paroxetine effectively reduce the severity of major
      depressive disorder in type II DM patients. There is need for further and longer
      lasting monitoring studies with more patients in order to determine whether there
      is any difference in terms of their effects on glycemic control.

PMID- 15847951
TI  - The roles of HRCT and clinical parameters in assessing activity of suspected
      smear negative pulmonary tuberculosis.
AB  - BACKGROUND: Smear-negative pulmonary tuberculosis (SNPTB) constitutes a major
      problem in countries with a moderate or high TB prevalence. The value of high
      resolution computed tomography (HRCT), chest x-ray and other clinical findings in
      determining activity of SNPTB were investigated. METHODS: The study population
      consisted of 85 patients with suspected SNPTB, of whom 52 were confirmed as
      active pulmonary TB according to either culture positivity for Mycobacteriun
      tuberculosis or demonstration of caseous granulomatous inflammation. The
      remaining 33 patients accepted inactive TB sequel. RESULTS: Cough and
      expectoration were significantly frequent in inactive group whereas chest pain
      was detected higher in active patients. Sensitivity, specificity, positive
      predictive value, negative predictive value and diagnostic accuracy of HRCT in
      detecting disease activity were 88, 88, 92, 83 and 88%, respectively.
      Centrilobular nodules, other non-calcified nodules, consolidation and cavity were
      significantly higher on HRCT in active group. Chest x-ray scores that were graded
      1 to 3 showed a linear trend for the disease activity. CONCLUSIONS: HRCT has good
      diagnostic value in detecting activity of SNPTB, and some clinical findings may
      help in predicting the activity.

PMID- 15847952
TI  - Peak expiratory flow and respiratory morbidity: a study among silica-exposed
      workers in India.
AB  - BACKGROUND: The present cross-sectional study was carried out among 136 quartz
      stone grinders with the objective of studying the peak expiratory flow (PEF) and
      the associated epidemiological factors. METHODS: Interview technique was used to
      record demographic characteristics and occupational history on a predesigned
      proforma, which included questionnaires regarding demographic, occupational and
      clinical characteristics. This was followed by complete medical examination and
      measurement of PEF using Spirovit SP-10. The study included 75 (55.1%) male and
      61 (44.9%) female silica-exposed workers. The mean age of the subjects was 31.77
      +/- 9.99 years whereas the mean duration of exposure was 2.74 +/- 1.65 years. The
      mean PEF was found to be 5.16 +/- 2.1 L/min. RESULTS: In the present study the
      PEF was significantly reduced in those having respiratory morbidity on both
      unadjusted and adjusted analyses. CONCLUSIONS: This suggests that along with the
      restrictive pathology caused by free silica dust, obstructive changes are also
      encountered in silica-exposed workers.

PMID- 15847953
TI  - The T1128C polymorphism of neuropeptide Y gene in a chinese population.
AB  - BACKGROUND: Several papers have shown that the T1128C polymorphism of the
      neuropeptide Y (NPY) gene was related to certain diseases and disorders. However,
      the allele frequency of the 1128C showed significant differences among some
      populations with different genetic backgrounds, being absent in Japanese and
      Korean populations. Therefore, this present study was aimed to explore whether
      the T1128C polymorphism of the NPY gene exists in a Chinese population. METHODS:
      A total of 304 newly diagnosed inpatients with coronary heart disease (CHD) were
      selected as the subjects in the present study. Polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis was performed to
      detect the T1128C polymorphism. RESULTS: Of the 304 CHD patients, only one
      patient showed the T1128/C1128 genotype in the NPY gene, the others were all the
      T1128/T1128 genotype. CONCLUSIONS: The T1128C polymorphism of the NPY gene is
      population specific and extremely low in a Chinese population.

PMID- 15847954
TI  - Seasonal variations of cerebral palsy births in northeastern Poland.
AB  - BACKGROUND: The objective of this report was to examine the seasonal variations
      on the incidence of cerebral palsy (CP) in Podlasie province, Poland in a
      retrospective case-control study. METHODS: Data were obtained from the Department
      of Pediatric Neurology and Rehabilitation. Selected babies were all born between
      January 1, 1990 and December 31, 1999; 212 children (116 boys, 96 girls) with CP
      were included in the study. We applied Cosinor analysis to examine the
      seasonality of CP births. RESULTS: The highest number of CP births occurred in
      spring and the lowest in winter, with intermediate values in summer and autumn.
      This seasonal pattern was significant for spring vs. winter. The peaks in CP
      births occurred in May and August. The lowest number of CP births occurred in
      February and December. We also demonstrated seasonal variation in CP births in
      girls and boys and Apgar score. Peaks in CP births in boys were noted in May and
      October and Apgar score in May and December, respectively. No significant
      relationship between mean temperature and Apgar score, low birthweight and
      asphyxia was found. CONCLUSIONS: These data suggest the seasonal patterns of CP
      births. Further studies should be performed with larger numbers of patients.

PMID- 15847955
TI  - Down syndrome.

PMID- 15847957
TI  - Does work really cause distress? The contribution of occupational structure and
      work organization to the experience of psychological distress.
AB  - This research examines the specific contribution of occupation and work
      organization conditions on psychological distress, based on a representative
      sample of 9501 workers in 419 occupations in Quebec, Canada. Multilevel
      regression models show that occupational structure accounts for 0.8% of variation
      in psychological distress. Among the constraints and resources related to work
      organization condition, physical and psychological demands, irregular schedules,
      and workplace harassment emerge as important determinants of psychological
      distress. The effects of work organization conditions do not vary across
      occupations. Family situation, support available from social networks outside
      work, and personal characteristics of individuals are also associated with
      psychological distress, but these factors do not moderate the effects of work
      organization conditions. Overall, the findings support the hypothesis that
      occupation and, to an even greater extent, "pathogenic" work organization
      conditions contribute independently to the experience of psychological distress.
      They also support the theoretical model conceptualizing psychological distress as
      the product of stress caused by constraints and resources brought to bear
      simultaneously by the agent's personality, structures of daily life, and
      macrosocial structures.

PMID- 15847958
TI  - Dealing with it: Black Caribbean women's response to adversity and psychological
      distress associated with pregnancy, childbirth, and early motherhood.
AB  - This paper focuses on Black Caribbean women's ideas about perinatal depression
      and the ways in which these are linked to coping with personal adversity. An
      epidemiological survey found that despite higher levels of social risk among
      Black Caribbean women living in the UK, they were no more likely than White
      British women to record above-threshold depression scores postnatally and were
      significantly less likely to have done so during pregnancy. In-depth interviews
      were undertaken to illuminate the models, experiences, and meaning of perinatal
      depression held by Black Caribbean women. Women's narratives suggested that they
      rejected 'postnatal depression' as a central construct for understanding
      responses to psychological distress associated childbirth and early motherhood.
      Rejection of depression as illness was associated with imperatives to normalise
      distress and a self-concept which stressed the importance of being 'Strong-Black
      Women' for maintaining psychological well-being. This identity served to
      reinforce notions of resilience, empowerment, and coping strategies characterised
      by the need to problem-solve practically, assertively, and materially. The study
      questions the utility of attaching psychiatric labels to the emotional and
      psychological distress experienced by Black Caribbean women around the perinatal
      period.

PMID- 15847959
TI  - Job strain, iso-strain, and the incidence of low back and neck injuries. A 7.5
      year prospective study of San Francisco transit operators.
AB  - Work-related musculoskeletal disorders account for the largest single category of
      lost-time occupational injury or disease episodes in industrialized countries. In
      this study we analyzed the impact of the psychosocial work environment,
      conceptualized by the demand-control-support model, on the incidence of low back
      and neck injury in a cohort of 1221 public transit operators followed for 7 years
      and 6 months. The two main exposure variables were "job strain" (mismatch of high
      psychological demands and low decision latitude) and "iso-strain" (job strain
      plus exposure to low social support at work). Analyses controlled for demographic
      factors, physical workload, and pain at baseline. For low back injuries,
      increased hazard rates were found for job strain and iso-strain based on
      tertiles, with hazard ratios (HR) of 1.30 (95% CI=0.96-1.75) and 1.41 (95%
      CI=0.98-2.01), respectively. Job strain and iso-strain based on median split or
      analyzed as continuous variables were not associated with low back injuries. For
      neck injuries, job strain and iso-strain based on median split showed HRs of 1.27
      (95% CI=0.99-1.63) and 1.33 (95% CI=1.01-1.77), respectively. Job strain and iso
      strain based on tertiles had HRs of 1.52 (95% CI=1.13-2.05) and 1.73 (95% CI=1.21
      2.45), respectively. When analyzed as continuous variables, a one-point increase
      on the job strain and iso-strain scales led to an 8% (95% CI=0.98-1.19) and 14%
      (95% CI=1.02-1.27) increased hazard of neck injuries, respectively. This study
      shows the importance of the psychosocial work environment in the etiology of
      musculoskeletal injuries among transit operators. Since reviews have shown that
      psychosocial workplace conditions in this occupational group can be changed,
      these findings indicate a potential for prevention at the workplace.

PMID- 15847960
TI  - Job insecurity and its association with health among employees in the Taiwanese
      general population.
AB  - As employers respond to intensive global competition through the deregulation of
      labor, job insecurity has become a widespread problem. It has been shown to have
      significant health impacts in a growing number of workers, but less is known
      about its social distribution, the mechanisms through which it may act, and the
      moderating effects of gender, socioeconomic position, and company size. Utilizing
      data from a national survey of a representative sample of paid employees in
      Taiwan, we examined the prevalence of job insecurity and its associations with
      psychosocial work characteristics and health status. A total of 8705 men and 5986
      women aged between 25 and 65 years old were studied. Information on perceived job
      insecurity, industrial and occupational types, psychosocial work characteristics
      as assessed by the Job Strain model, and various measures of health status were
      obtained by a self-administered questionnaire. The overall prevalence of job
      insecurity was high (50%). Job insecurity was more prevalent among employees with
      lower education attainment, in blue-collar and construction workers, those
      employed in smaller companies, and in older women. Insecure employees also
      reported lower job control, higher job demands, and poor workplace social
      support, as compared with those who held secure positions. Regression analyses
      showed that job insecurity was strongly associated with poor health, even with
      adjustment of age, job control, job demands, and work place social support. The
      deleterious effects of job insecurity appeared to be stronger in men than women,
      in women who held managerial or professional jobs than women in other employment
      grades, and in those working in larger companies than smaller ones. The findings
      of this study suggest that perceived job insecurity is an important source of
      stress, and it is accompanied with adverse psychosocial work conditions and poor
      health. High-risk groups were identified for further investigation.

PMID- 15847961
TI  - Ethnic variation in health and the determinants of health among Latinos.
AB  - The purpose of this research is to document and explain ethnic variation in
      health among Latino adults in the United States. Results of analyses of data
      pooled from the 1997-2001 National Health Interview surveys reveal that health
      patterns are clearly different among Latino ethnic groups. Mexicans have health
      advantages, whereas Puerto Ricans experience health disparities. Cubans and
      Dominicans reveal a mix of health disparities and advantages, depending on the
      health outcome. The effects of social determinants of health are also contingent
      upon ethnicity. For example, worse health is associated with higher levels of
      socioeconomic status (SES) and acculturation among Mexicans, but with lower
      levels of SES and acculturation among Latinos whose origins are from Caribbean
      islands. We conclude that racial/ethnic comparative health research should avoid
      pan-ethnic groupings, and explicitly acknowledge ethnic group distinctiveness.

PMID- 15847962
TI  - Primary care, race, and mortality in US states.
AB  - This study used US state-level data from 1985 to 1995 to examine the relationship
      of primary care resources and income inequality with all-cause mortality within
      the entire population, and in black and white populations. The study is a pooled
      ecological design with repeated measures using 11 years of state-level data
      (n=549). Analyses controlled for socioeconomic and demographic characteristics.
      Contemporaneous and time-lagged covariates were modeled, and all analyses were
      stratified by race/ethnicity. In all models, primary care was associated with
      lower mortality. An increase of one primary care doctor per 10,000 population was
      associated with a reduction of 14.4 deaths per 100,000. The magnitude of primary
      care coefficients was higher for black mortality than for white mortality. Income
      inequality was not associated with mortality after controlling for state-level
      sociodemographic covariates. The study provides evidence that primary care
      resources are associated with population health and could aid in reducing
      socioeconomic disparities in health.

PMID- 15847963
TI  - Arab immigrants: a new case for ethnicity and health?
AB  - Community-based studies of Arab Americans point to significant health problems
      among the immigrants, a finding that runs contrary to theories of immigrant
      selectivity. This study is the first to use nationally representative data to
      test this question. Using new questions that identify region of birth in the 2000
      and 2001 National Health Interview Surveys, we compare the self-rated health and
      activity limitation of Arab immigrants to US-born white Americans and test the
      extent to which social, demographic, and immigrant characteristics account for
      observed disparities. The results find that Arab immigrants do not significantly
      differ from US-born whites in their self-rated health and are less likely to
      report limitations in activity. Length of time in the US has no composite effect
      on health; however, US citizenship does. Compared to the most recent immigrant
      arrivals, Arab immigrants who are citizens report worse health while their peers
      who are not officially American (non-citizens) do not, regardless of their
      duration of US residency. Contrary to prior studies on Arab health, we find that
      Arab immigrants are not uniformly disadvantaged in their health outcomes and that
      their health profile is more diverse than currently documented. The results also
      suggest that controlling for years of US residency may be insufficient for
      capturing the cumulative effects of acculturation on immigrant health. We
      conclude by suggesting avenues of future research for capturing heterogeneity
      among emergent ethnic populations such as Arab Americans.

PMID- 15847964
TI  - Income inequality and weight status in US metropolitan areas.
AB  - Prior empirical studies have demonstrated an association between income
      inequality and general health endpoints such as mortality and self-rated health,
      and findings have been taken as support for the hypothesis that inequality is
      detrimental to individual health. Unhealthy weight statuses may function as an
      intermediary link between inequality and more general heath endpoints. Using
      individual-level data from the 1996-98 Behavioral Risk Factor Surveillance
      System, we examine the relationship between individual weight status and income
      inequality in US metropolitan areas. Income inequality is calculated with data
      from the 1990 US Census 5% Public Use Microsample. In analyses stratified by race
      sex groups, we do not find a positive association between income inequality and
      weight outcomes such as body mass index, the odds of being overweight, and the
      odds of being obese. Among white women, however, we do find a statistically
      significant inverse association between inequality and each of these weight
      outcomes, despite adjustments for individual-level covariates, metropolitan-level
      covariates, and census region. We also find that greater inequality is associated
      with higher odds for trying to lose weight among white women, even adjusting for
      current weight status. Although our findings are suggestive of a contextual
      effect of metropolitan area income inequality, we do not find an increased risk
      for unhealthy weight outcomes, adding to recent debates surrounding this topic.

PMID- 15847965
TI  - Access, utilization, quality, and effective coverage: an integrated conceptual
      framework and measurement strategy.
AB  - Health systems can primarily improve the health of individuals and populations by
      delivering high-quality interventions to those who may benefit from them. We
      propose a concept of effective coverage as the probability that individuals will
      receive health gain from an intervention if they need it. Understanding the
      extent to which health systems are delivering key interventions to those who will
      benefit from them and the factors that explain gaps in delivery are a critical
      input to decision-making at the local, national and global levels. We develop an
      integrated conceptual framework for monitoring and analyzing the delivery of high
      quality interventions to those who need them. This framework can help clarify the
      inter-relationships between notions of access, demand for care, utilization, and
      coverage on the one hand and highlight the requirements for health information
      systems that can sustain this type of analysis. We discuss measurement strategies
      and demonstrate the concept by means of a simple simulation model.

PMID- 15847966
TI  - Psychosocial work characteristics and incidence of newly diagnosed depression: a
      prospective cohort study of three different models.
AB  - This study explored the association between psychosocial work characteristics and
      incidence of depression as indicated in three complementary models (the Job
      Strain Model, the Team Climate Model, and the Procedural Justice Model).
      Participants were 4815 Finnish hospital personnel (4278 women and 537 men) free
      from diagnosed depression at entry into the study. A baseline survey in 1998
      measured psychosocial work characteristics, health-related behaviours,
      psychological distress, and doctor-diagnosed depression. The factor analysis of
      pooled questionnaire items on psychosocial work characteristics supported a five
      factor solution with the following distinct dimensions: team climate, relational
      justice, procedural justice, job control, and job demands. Items in these
      dimensions were used as scales and job strain was modelled as a combination of
      job demands and job control. A follow-up survey in 2000 identified 225 incident
      cases of depression. After adjustment for age, sex and income, poor team climate,
      low procedural justice, and low relational justice were associated with a higher
      risk of new depression, the odds ratios (ORs) 1.58 (95% confidence interval (CI)
      1.11-2.24), 1.45 (95% CI 1.03-2.04), and 1.39 (95% CI 1.00-1.96), respectively.
      After additional adjustment for lifestyle factors and exclusion of those with
      psychological distress at baseline, there was still an association between poor
      team climate and risk of depression (ORs 1.55 and 1.75, respectively). Job
      control, work demands, and job strain did not predict the 2-year incidence of
      depression, and the effects of all psychosocial work characteristics were
      attenuated when entered simultaneously in the model. In conclusion, work unit
      social factors seem to be predictive of subsequent doctor-diagnosed depression,
      but other aspects of psychosocial work environment may also be important.

PMID- 15847967
TI  - The role of psychosocial factors in explaining socio-economic differences in
      mobility decline in a chronically ill population: results from the GLOBE study.
AB  - In chronically ill patients, mobility develops more unfavorably in persons with
      low socio-economic status (SES) than in their better-off counterparts. Using
      longitudinal data from the Dutch GLOBE study (a study of health and living
      conditions in Eindhoven and its surroundings), the present study examines whether
      psychosocial factors can explain socio-economic differences in mobility decline,
      independent of disease severity, co-morbidity, and health-related behavior in a
      chronically ill population. Data were from 1384 men and woman, aged 15-74 years,
      suffering from at least one of the four chronic diseases: asthma/COPD, heart
      disease, diabetes mellitus, and low back pain. Three indicators of SES were used:
      education, occupational class, and income. Change in physical mobility between
      1991 and 1997 was measured with the Nottingham Health Profile (NHP). Psychosocial
      factors were measured extensively and included life events, long-term
      difficulties, coping styles, social support, and personality characteristics. Low
      occupational level and low income predicted an increased risk of mobility decline
      in comparison to people with a higher occupational level and income, even after
      controlling for sociodemographics, disease severity, co-morbidity, and health
      related behavior. Additional adjustment for psychosocial factors hardly reduced
      the SES-related odds ratios of mobility decline. We conclude that psychosocial
      factors (and also health-related behaviors, disease severity and co-morbidity)
      cannot explain socio-economic differences in mobility decline in a chronically
      ill population. Our findings will not give us new tools for prevention and
      intervention strategies in order to reduce physical disability and particularly
      the SES differences therein.

PMID- 15847968
TI  - Resisting medicines: a synthesis of qualitative studies of medicine taking.
AB  - The study aimed to synthesise qualitative studies of lay experiences of medicine
      taking. Most studies focused on the experience of those not taking their medicine
      as prescribed, with few considering those who reject their medicines or accept
      them uncritically. Most were concerned with medicines for chronic illnesses. The
      synthesis revealed widespread caution about taking medicines and highlighted the
      lay practice of testing medicines, mainly for adverse effects. Some concerns
      about medicines cannot be resolved by lay evaluation, however, including worries
      about dependence, tolerance and addiction, the potential harm from taking
      medicines on a long-term basis and the possibility of medicines masking other
      symptoms. Additionally, in some cases medicines had a significant impact on
      identity, presenting problems of disclosure and stigma. People were found to
      accept their medicines either passively or actively, or to reject them. Some were
      coerced into taking medicines. Active accepters might modify their regimens by
      taking medicines symptomatically or strategically, or by adjusting doses to
      minimise unwanted consequences, or to make the regimen more acceptable. Many
      modifications appeared to reflect a desire to minimise the intake of medicines
      and this was echoed in some peoples' use of non-pharmacological treatments to
      either supplant or supplement their medicines. Few discussed regimen changes with
      their doctors. We conclude that the main reason why people do not take their
      medicines as prescribed is not because of failings in patients, doctors or
      systems, but because of concerns about the medicines themselves. On the whole,
      the findings point to considerable reluctance to take medicine and a preference
      to take as little as possible. We argue that peoples' resistance to medicine
      taking needs to be recognised and that the focus should be on developing ways of
      making medicines safe, as well as identifying and evaluating the treatments that
      people often choose in preference to medicines.

PMID- 15847969
TI  - Conceptualizing mainstream health care providers' behaviours in relation to
      complementary and alternative medicine.
AB  - There has been an explosion of literature on the attitudes of a variety of health
      care providers, particularly physicians, to the growing utilization of
      complementary and alternative medicines and modalities (CAM). What is most
      seriously lacking is a conceptual framework that helps to distill this mountain
      of literature into a manageable and more understandable amount. In this paper, we
      address these important issues by examining the literature that surveys the
      attitudes and behaviour of providers regarding CAM comparatively across the
      professions of medicine and nursing and across settings. We do so by drawing upon
      existing, more general theoretical contributions to the area of CAM in order to
      propose a comparative conceptual framework with which to interpret the diverse
      and at times discrepant results of this body of research.

PMID- 15847970
TI  - HIV and intimate partner violence among methadone-maintained women in New York
      City.
AB  - Intimate partner violence (IPV) has been recognized as a risk factor for HIV and
      sexually transmitted infections (STIs) among women, particularly among those who
      are drug involved. This study examines the temporal relationships between sexual
      and/or physical partner violence (IPV) and sexual risk of HIV/STI transmission in
      a longitudinal study with a random sample of 416 women enrolled in methadone
      maintenance treatment programs in New York City. Two hypotheses are tested:
      whether sexual risk-related factors or risk reduction behavior leads to
      subsequent IPV (H1); and whether IPV decreases likelihood of subsequent risk
      reduction behavior (i.e., requesting to use condoms) or increases likelihood of
      certain sexual risk-related factors (i.e., inconsistent condom use, having
      unprotected anal sex, having more than one partner, exchanging sex for drugs or
      money, having had an STI, being HIV positive, having a partner who engaged in HIV
      risk) (H2). Participants were interviewed at three waves: baseline, six months
      and twelve months. Hypotheses were examined using propensity score matching and
      multiple logistic regression analyses. The prevalence rate of any physical or
      sexual IPV was 46% at baseline. Findings for H1 indicate that women who reported
      always using condoms at wave 2 were significantly less likely than women who
      reported inconsistent or no condom use to experience subsequent IPV at wave 3.
      Similarly, increased risk of IPV at wave 3 was associated with self-reported STIs
      (OR=2.0, p=.03), and unprotected anal sex (OR= 2.0, p<.01); always requesting
      that partners use condoms was associated with a significant decrease in
      subsequent IPV (OR=.18, p<.01). Findings for H2 suggest that IPV at wave 2
      decreased the subsequent likelihood of always using condoms at wave 3 (OR=.41,
      p<.01) and always requesting that a partner use condoms (OR=.42, p=.02). The
      implications of the findings for HIV prevention interventions for women on
      methadone are discussed.

PMID- 15847971
TI  - Social capital and young adolescents' perceived health in different sociocultural
      settings.
AB  - We conducted a cross-national study to examine the association between
      neighbourhood socioeconomic deprivation, social capital and child health in two
      countries and multiple ethnic groups. For our analysis we used data from (1) the
      Project on Human Development in Chicago Neighborhoods (PHDCN), USA and (2) the
      Maastricht Quality of Life study (MQoL), the Netherlands. Both the PHDCN and the
      MQoL collected data on objective neighbourhood socioeconomic deprivation,
      subjective neighbourhood social capital (i.e. informal social control, ISC,
      social cohesion and trust, SC&T), and children's perceived health. For the
      present analyses, 11- and 12-year olds were selected. Multilevel analyses were
      conducted using both neighbourhood level and individual-level data. Lower
      socioeconomic deprivation scores and higher levels of ISC as well as SC&T were
      associated with higher levels of children's perceived health, in both Maastricht
      and the Chicago Hispanic subsample, but not in the Chicago non-Hispanic samples.
      The results suggest that associations between the wider social environment and
      health outcomes vary across different populations and cross-national contexts.

PMID- 15847972
TI  - The importance of eating rice: changing food habits among pregnant Indonesian
      women during the economic crisis.
AB  - This article presents qualitative and quantitative research findings on food
      habits of pregnant Indonesian women in relation to the economic crisis that arose
      in 1997. Between 1996 and 1998, dietary intakes were estimated for 450 pregnant
      women in Central Java. Between January and June 1999, four focus group
      discussions, 16 in-depth interviews and four non-participant observations were
      held with women, two in-depth interviews were held with traditional birth
      attendants, and four with midwives. Women were categorized as urban or rural,
      rich or poor, and according to rice field ownership. The women reported that
      before the crisis they bought more foods and cooked more meals and snacks. During
      the crisis, cooking methods became simpler and cooking tasty foods was more
      important than cooking nutritious foods. This involved using plenty of spices and
      cooking oil, but reducing the use of expensive nutritious foods. The herbal drink
      jamu was drunk by 15% of pregnant women; its consumption was lower during than
      before the economic crisis. Twenty-six percent of the women avoided certain foods
      due to food taboos, and most of these women avoided beneficial foods; this
      phenomenon decreased during the crisis among the rich and the rural, poor,
      landless women. In spite of increased prices for rice, women did not decrease
      their rice consumption during the crisis because rice was believed to have the
      highest value for survival, to provide strength during pregnancy and delivery,
      and to be easier to store and cook. Finally, children and husbands had highest
      priority in being served food, and women were the last to eat.

PMID- 15847973
TI  - The contribution of lone parenthood and economic difficulties to smoking.
AB  - Smoking is more prevalent among lower socioeconomic status groups, among those
      who perceive economic difficulties and among lone mothers. Less is known of how
      these factors contribute to smoking independently. The aim of this study was
      first to examine the association between smoking and both economic difficulties
      and lone parenthood. We then also studied to what extent smoking among people
      experiencing economic difficulties and lone parenthood is due to other factors
      such as socioeconomic status and social relations. The data derive from surveys
      conducted among the employees of the City of Helsinki, Finland, in 2000 and 2001
      including 6243 respondents aged 40-60 yr (response rate 68%). The measures were
      daily smoking, economic difficulties and family type, as well as socioeconomic
      status (education, occupational social class, household income, housing tenure)
      and social relations. The more had respondents experienced economic difficulties,
      the more prevalent was their smoking. Smoking among lone parents was more common
      than among parents living together; this was true for both men and women. After
      controlling for socioeconomic status and housing tenure, the association between
      smoking and economic difficulties, as well as that between smoking and lone
      parenthood, attenuated but remained statistically significant. However, after
      controlling for social relations the associations became stronger. Both economic
      difficulties and lone parenthood were associated with smoking independent of
      education, occupational social class, household disposable income, housing tenure
      or social relations for both men and women.

PMID- 15847974
TI  - Fertility history and health in later life: a record linkage study in England and
      Wales.
AB  - Women born at different periods within the 20th century in England and Wales have
      followed varying fertility pathways with large changes in, for example,
      proportions having no children or only one child. Among the consequences of these
      changes may be effects on women's health later in life. Links between fertility
      histories and later health and mortality have been investigated in several
      studies, but in many of these socio-economic characteristics have not been
      allowed for, even though there are socio-economic differences in both fertility
      and mortality patterns and results are conflicting. Here we analyse associations
      between the fertility histories of women born 1911-1940 in England and Wales and
      their mortality and health status after age 50. We used data from the Office for
      National Statistics Longitudinal Study; a record linkage study of approximately
      1% of the population initially based on those enumerated in the 1971 Census of
      England and Wales. We used survival analysis to investigate the effects of
      parity, short birth intervals, and timing of fertility on mortality from age 50
      to the end of 2000, controlling for a range of relevant socio-demographic
      characteristics. For survivors to 1991, we additionally used logistic regression
      to model probability of having a limiting long-term illness in 1991. We found
      that nulliparous women and women with five or more children had significantly
      higher mortality than other women, and that in the oldest groups women with just
      one child also had raised mortality. Women who had been teenage mothers had
      higher mortality and higher odds of poor health than other parous women. Mothers
      with short birth intervals, including mothers of twins, also had elevated risks
      in some cohorts. Late childbearing (after age 39) was associated with lower
      mortality. Personal demographic history is an important factor to consider in
      analyses of health and mortality variations in later life. More research is
      needed to further elucidate causal pathways.

PMID- 15847975
TI  - Where there is no state: household strategies for the management of illness in
      Chad.
AB  - The current structure of the health care system in Chad, which is characterized
      by a weak public health system and a nascent and largely unaffordable private
      sector, raises questions about how low-income households manage illnesses. These
      questions are also compelling because of claims about the potential of oil
      related investments to restructure the current landscape of care over the next 25
      30 years. This paper focuses on household strategies for treating episodes of
      malaria reported in an on-going, longitudinal study of household health and
      access to care in Chad. Treatment of malaria outside the health care system is
      widespread in endemic areas, therefore it is not surprising that low-income
      households in this study rely heavily on unregulated drug markets for care.
      However, the paper shows how self-medication and the use of these drug markets
      are shaped by the current organization and delivery of care, and are not simply
      the outcome of a lack of information about the dangers associated with such
      practices. The paper also shows the consequences of this particular constellation
      of services for health in low-income households. We see, for example, the
      emergence of regimes for managing illness that consist of keeping debilitating
      symptoms at bay through the use of intermittent, sub-optimal therapies that
      provide a temporary reprieve but not a 'cure.' We also see that households ignore
      health problems--absorbing them into the experience of everyday life--that might
      elsewhere demand attention. When illnesses appear as crises it is often because
      cash-strapped households are unable to sustain this type of management regime,
      and easily treatable problems spiral out of control. Whether and how the
      experiences of the low-income households described in this paper will be impacted
      by the public investment of oil revenues in the health sector is the question our
      longitudinal study is designed to address.

PMID- 15847976
TI  - Biases in internet sexual health samples: comparison of an internet sexuality
      survey and a national sexual health survey in Sweden.
AB  - The internet is becoming a favored technology for carrying out survey research,
      and particularly sexual health research. However, its utility is limited by
      unresolved sampling questions such as how biased internet samples may be. This
      paper addresses this issue through comparison of a 'gold standard' random
      selection population-based sexual survey (The Swedish Sexual Life Survey) with an
      internet-based survey in Sweden which used identical demographic, sexual and
      relationship questions, to ascertain the biases and degree of comparability
      between the recruitment methods. On the internet questionnaire, there were
      significant differences between males and females on all the measured indices.
      There were no significant differences in proportions of males and females, or
      nationality, between the two samples. However, the internet samples for both
      males and females were significantly more likely to be younger, originally from
      and currently living in a major city, better educated, and more likely to be
      students and less likely to be retired. Relationship variables were less likely
      to be significantly different between samples: there were no differences for
      males or females between the SSS and the internet samples on having been in a
      committed relationship, and how they met their present partner, nor for males in
      having discussed separation in the past year. However, there was a higher
      proportion of people attracted to the same sex, and higher numbers of sex
      partners (as well as a higher proportion of people reporting no sex) in the past
      year, in the internet sample. These data suggest that apart from the demographics
      of age, location, and education, currently being in a committed relationship, and
      the number of sex partners in the past year, internet samples are comparable for
      relationship characteristics and history with a national sexual life survey.
      Comparison of internet data with random survey data in other western countries
      should occur to determine if these patterns are replicated.

PMID- 15847977
TI  - Adjuvant anthracycline-based chemotherapy for early breast cancer: do the dose
      and schedule matter?
AB  - The rationale to justify the use of anthracyclines as adjuvant therapy for breast
      cancer is their proven superiority over CMF. Indeed, this has been demonstrated
      by a number of randomised clinical trials and recently confirmed by the Oxford
      meta-analysis. Nevertheless, the absolute benefit is modest (on average 4%), and
      with the cost of increased toxicity. Interestingly, many individual trials were
      unable to confirm the role of anthracyclines in early breast cancer, though most
      of these were either underpowered to show such small differences, or had
      inappropriate experimental arms. On the other hand, several trials included in
      the meta-analysis also had inadequate control arms. So far, probably only three
      trials were able to individually confirm this benefit: the American INT 0102, the
      Canadian MA5 and more recently, the British NEAT/NCTBG. Numerous different
      anthracycline schedules have been used as adjuvant therapy, many of these having
      never been compared to CMF. Unfortunately, as research is moving towards other
      more important questions, many of these uncertainties may never be clarified. In
      this paper, we review the current evidence behind some of the most commonly used
      anthracycline schedules.

PMID- 15847978
TI  - Adjuvant chemotherapy in the treatment of high grade gliomas.
AB  - Standard treatment of high-grade glioma (HGG) is based on surgery followed by
      limited field radiotherapy, while the role of chemotherapy is still
      controversial. Many randomized trials addressing the role of post-radiation or
      "adjuvant" chemotherapy have been conducted in the last three decades, yielding
      negative or inconclusive results. A statistically significant survival benefit
      with adjuvant chemotherapy has been demonstrated in two meta-analyses. The
      estimated absolute increase in survival is modest (10% at 1 year) but
      significant, and it appears independent of age, Performance Status and histology.
      Nitrosourea-based regimens were long considered the standard chemotherapy options
      for HGG, but their toxicity is not negligible. Temozolomide (TMZ) is a promising
      new drug that seems to be effective in patients with recurrent disease.
      Clinically and statistically significant survival benefit with the administration
      of TMZ concomitant and after radiotherapy has been recently demonstrated,
      establishing a new standard in HGG adjuvant treatment. Randomized comparisons
      with nitrosoureas are lacking and represent a major issue to be studied in future
      phase III trials.

PMID- 15847979
TI  - Pharmacology of oxaliplatin and the use of pharmacogenomics to individualize
      therapy.
AB  - Oxaliplatin is a relatively new platinum analogue that is currently used in
      pharmacotherapy of metastatic colorectal cancer. Its dose-limiting toxicity is
      sensory neuropathy, which can be modulated by infusion of calcium and magnesium.
      Oxaliplatin exerts its anti-tumour effects by platinum-adduct formation, binding
      to cellular proteins and possibly interfering with RNA synthesis as well. If they
      are not removed from DNA, oxaliplatin adducts are lethal. Cellular defense
      mechanisms prevent adduct formation (e.g., glutathione-S-transferase) or remove
      DNA adducts (e.g., nucleotide excision repair). Depending on the activity of
      necessary enzymes in these cellular defense pathways, oxaliplatin induced damage
      varies from one individual to another. There is growing evidence that
      polymorphisms in genes coding for DNA repair enzymes and metabolic inactivation
      routes contribute to the interindividual differences in anti-tumour efficacy and
      toxicity of oxaliplatin. Single nucleotide polymorphisms (SNPs) may yield
      inactive enzymes, or increased gene transcription and hence increased enzyme
      production. This review covers findings of recent investigations on the
      associations of SNPs and clinical outcome after oxaliplatin chemotherapy in
      metastatic colorectal cancer.

PMID- 15847980
TI  - Branchiogenic carcinoma--conceptual or true clinico-pathological entity?
AB  - The existence of branchiogenic carcinoma remains controversial. According to some
      authors, this malignancy is more conceptual than a true clinicopathologic entity.
      The originally proposed diagnostic criteria of branchiogenic carcinoma have been
      subsequently challenged. Many reports regarding primary branchiogenic carcinoma
      have failed to provide sufficient evidence to distinguish this entity from nodal
      metastases arising from unrecognized primary tumours. There is growing evidence
      that the majority of branchiogenic carcinomas are in fact cystic metastases from
      oropharyngeal carcinoma, most commonly originating in the tonsils, and not true
      carcinomas arising in a branchial cleft cyst. The missing link between branchial
      cyst and branchiogenic squamous cell carcinoma could be fulfilled by the
      occurrence of in situ branchial cyst carcinomas, yet such cases are extremely
      rare. Isolated cystic neck lesions, necessitate a thorough search for a primary
      tumour, similarly to other occult primaries presenting with cervical metastases.
      The treatment of cervical cyst with dysplasia or carcinoma in situ includes
      complete surgical excision. The true branchiogenic carcinomas should be
      approached with postoperative irradiation to the half neck. A cervical metastatic
      cystic squamous carcinoma of unknown origin should be treated as for other cases
      of occult primaries, i.e. with surgery and radiotherapy. The data on the
      prognosis of branchiogenic carcinoma are scarce, though long-term survival has
      been reported. Further histopathologic and clinical studies are warranted in
      order to better understand the biology and natural history of cervical cystic
      lesions. The existence of true branchiogenic carcinoma remains to be verified
      with new clinical and molecular criteria.

PMID- 15847981
TI  - The causes and treatment of bone loss associated with carcinoma of the breast.
AB  - Despite an increasing incidence, the outlook for women with early breast cancer
      has improved considerably over recent years with a steady fall in the death rate
      in most western countries. This is due, at least in part, to the widespread use
      of adjuvant systemic therapy. However, some of these treatments have adverse
      effects on bone metabolism with increased bone loss which may result in
      osteoporosis and associated fractures. Most of the effects on bone are mediated
      by endocrine changes, either induction of an early menopause by chemotherapy and
      ovarian ablation, or further suppression of postmenopausal circulating oestrogens
      by aromatase inhibitors. There may also be direct effects of chemotherapy on bone
      cell function. The pathophysiology of osteoporosis in breast cancer patients, the
      methods of assessment and treatment options are reviewed. Bone health is a highly
      topical issue in breast cancer with the emergence of data supporting the use of
      several years of treatment with aromatase inhibitors. Guidelines on who and how
      to screen for bone loss, and simple, safe strategies for treatment to prevent
      osteoporosis are presented.

PMID- 15847982
TI  - Little evidence available on treatments for basal cell carcinoma of the skin.

PMID- 15847983
TI  - No clear evidence for adjuvant therapy in people with stage II colon cancer.

PMID- 15847984
TI  - Assay directed chemotherapy: clinical benefit remains unclear.

PMID- 15847985
TI  - High-quality evidence in oncology from 1st September to 14th October 2004: a
      summary.

PMID- 15847986
TI  - In vivo behaviour of vesicular urokinase.
AB  - Thromboembolic diseases including deep vein thrombus (DVT) are major causes of
      morbidity and mortality. Detection of DVT in low extremities is difficult. There
      are some accepted imaging techniques in clinic but most of them have several
      disadvantages limiting their effective use. Because of this, researchers are
      still performed to develop a rapid, specific means of detecting and/or imaging
      venous thrombi-based on the changing composition of the thrombus. Urokinase,
      fibrinolytic enzyme isolated form human urine, is a direct activator of
      plasminogen. In thrombus formation, plasminogen seems to be trapped in or
      absorbed onto fibrin matrix thus leading to a localised concentration of
      plasminogen. This suggests that radiolabelled urokinase would be a suitable
      compound for the detection of thrombi. The most important disadvantage of this
      enzyme is short plasma half life. To overcome this problem, it was decided to
      encapsulate the enzyme in drug delivery systems such as liposomes, niosomes or
      sphingosomes. In this study, we prepared, characterized and monitored the
      biodistribution of three types of vesicular systems containing urokinase. All
      types of prepared vesicles show in vitro an acceptable encapsulation, stability
      and release profile. Thrombus uptake was increased by encapsulation of urokinase
      into vesicles.

PMID- 15847987
TI  - A novel water-soluble cyclosporine A prodrug: ocular tolerance and in vivo
      kinetics.
AB  - The purpose of this study is to demonstrate that a novel water-soluble prodrug of
      cyclosporine A (CsA) intended for topical ocular administration, does not induce
      eye irritation in a rabbit model and is able to generate therapeutic
      concentrations of CsA in the precorneal area immediately after administration.
      The eye irritancy of the prodrug and CsA control solution was assessed by the
      Draize test and by confocal laser ophthalmoscopy (CLSO). Residence time and tear
      concentrations of prodrug and CsA in the rabbit eye were assessed by HPLC. The
      Draize test showed an excellent tolerance for the prodrug solution while the
      reference CsA oil solution induced lachrymation and irritation. The CLSO-measured
      corneal lesions, subsequent to treatment with the prodrug and reference
      solutions, were 3% and 9%, respectively. The prodrug transformed rapidly, leading
      to relatively stable CsA concentrations in tears with a maximal concentration of
      94 microg ml(-1) over the observation period. This study demonstrated that the
      prodrug solution was well tolerated and that clinically significant CsA tear
      concentrations were achieved. UNIL088 is a promising molecule in the treatment of
      immune-related disorders of the eye.

PMID- 15847988
TI  - Continuous variation data: 1:1 or 2:2 weak complexes?
AB  - An attempt to distinguish between 1:1 and 2: 2 weak complexes from continuous
      variation data is given. A modification of the Heller and Schwarzenbach's method
      which involves the use of the absorbance ratio y=A/A(lim) (once the limiting
      absorbance, A(lim) is known) may be applied to 1:1 weak complexes. This allows
      checking if the slope obtained is close to the theoretical value of -0.25. A
      curvature appears and the residuals have a pattern when a wrong 1:1 model is
      selected for a true 2:2 stoichiometry.

PMID- 15847989
TI  - Polycations enhance emulsion-mediated in vitro and in vivo transfection.
AB  - To enhance the in vitro and in vivo transfection activity of the cationic lipid
      emulsion (LE), three natural polycations, protamine sulfate (PS), poly-L-lysine
      and spermine, were selected as DNA condensing active agents. Formation of the
      LE/polycation/DNA ternary complexes was identified by using agarose gel
      retardation study. The structure of these complexes was characterized by
      measuring the complex size and the decrease of the DNA fluorescence in the
      presence of ethidium bromide (EtBr). By adding a polycation, the particle size of
      the complex decreased, and DNA in the complex became highly condensed and
      resistant to intercalation of EtBr. Among the polycations, PS yielded the most
      highly compacted ternary complex. In vitro and in vivo transfection activities of
      the complexes were determined using various cell lines and Balb/c mouse
      intravenously and intranasally, respectively. The transfection activity of the
      ternary complex increases by at least 2.5-5-fold in vitro cell culture system in
      the presence of 80% serum as well as in vivo mouse system, as compared with
      LE/DNA binary complexes. More importantly, after intravenous and intranasal
      administrations, the in vivo transfection efficiency of the LE/PS/DNA complex was
      ca. 30 and 50 times higher than that of the liposome (LP)/DNA complex in spleen
      and lung, respectively. On the other hand, cell toxicity of the ternary complex
      is lower than that of binary complex. Thus, we conclude that the pre-condensation
      of DNA with polycations can be a promising approach to further increase in vitro
      and in vivo transfection efficiency of cationic lipid emulsion.

PMID- 15847990
TI  - Intercalation of the radical scavenger ferulic acid in hydrotalcite-like anionic
      clays.
AB  - Hydrotalcite is a biocompatible lamellar anionic clay formed by double hydroxide
      layers with a metal cation coordinating four OH groups. The different layers are
      held together by anionic hosts that can be replaced by a simple ion-exchange
      process. The synthetic Mg-Al-hydrotalcite was used to intercalate ferulic acid, a
      compound that shows antioxidant properties due to its free radical scavenger
      capacity. Analysis of the intercalated compound showed a good intercalation
      percentage (35.53%) accompanied by an increase of the interlayer space from 7.8A
      (chloride form) to 17.1A due to the presence of the ferulate. The intercalation
      product was stable in water, did not show any significant degradation after UV
      irradiation, had a higher capacity of UV absorption in comparison to both the
      pure ferulic acid and ferulic acid-hydrotalcite chloride physical mixture. The
      intercalated compound was formulated in a siliconic cream and the ferulate in
      vitro release profiles determined.

PMID- 15847991
TI  - Surfactant solubility and aggregate orientation in hydrofluoroalkanes.
AB  - PURPOSE: To find surfactants soluble in the two hydrofluoroalkane (HFA)
      propellants, HFA-134a and HFA-227ea; to compare surfactant solubility in the two
      propellants with those in 2H,3H-decafluoropentane (DFP) in order to assess
      latter's suitability as a liquid model propellant and to investigate surfactant
      aggregation and aggregate orientation in HFAs. METHODS: To assess surfactant
      solubility, HFA was added to a known amount of surfactant until dissolution was
      visibly apparent. An iodine solubilization method was used to determine
      surfactant aggregation behaviour in DFP. Fluorescence spectroscopic
      investigations on the surfactant orientation in aggregates were carried out in
      HFAs using a microviscosity sensitive fluorescent probe (1,3-dipyrenylpropane).
      The aim was to assess viscosity changes in the microenvironment of this
      lipophilic probe upon incorporation into surfactant aggregates. RESULTS: Soluble
      surfactants could be found among the polyoxyethylene-ethers and POE-PPO-block
      copolymer surfactants. Solubility in DFP appears to correlate with solubility in
      HFA-134a, but not HFA-227ea. Iodine solubilization indicates micellization of
      Brij 30 in DFP at a cmc (type II association behaviour). L-44 in DFP, on the
      other hand, does not exhibit a well defined cmc, but shows continuous surfactant
      aggregation (type I association behaviour). The fluorescence spectroscopic
      studies showed evidence for probe incorporation into surfactant aggregates in
      HFAs. CONCLUSIONS: DFP proved to be a good model for HFA-134a only. An L1
      aggregate orientation was shown for surfactants in HFAs and is in marked contrast
      to the chlorofluorocarbon propellant where a L2-aggregate orientation exists.

PMID- 15847992
TI  - In vitro and in vivo studies of cyclosporin A-loaded microspheres based on
      copolymers of lactide and epsilon-caprolactone: comparison with conventional PLGA
      microspheres.
AB  - A hydrophobic peptide, cyclosporin A (CyA), was incorporated in microspheres
      based on poly(lactide-b-epsilon-caprolactone) (P(LA-b-CL), LA/CL (in molar
      ratio): 78.7/21.3 and 48.1/51.9) and poly(lactide-co-glycolide) (PLGA, LA/GA:
      80/20) using oil-in-water (O/W) emulsion solvent evaporation method. The
      microspheres were characterized by SEM, DSC and X-ray diffraction, and CyA
      release rate was determined by HPLC. It was revealed that CyA can be efficiently
      loaded into all the microspheres (exceed 96%). Compared to PLGA microspheres,
      P(LA-b-CL) microspheres liberated CyA more rapidly. Within the first day, about
      75, 50 and 12% of CyA released from P(LA-b-CL) (48.1/51.9), P(LA-b-CL)
      (78.7/21.3) and PLGA microspheres, respectively, which can be attributed to the
      partial crystallization occurring in P(LA-b-CL) microspheres. CyA levels in whole
      blood were also tested. In comparison with PLGA microspheres, P(LA-b-CL)
      microspheres provided a higher blood level of CyA. The maximum CyA concentration
      in whole blood (approximately 520, 450 and 400 ng ml(-1) for P(LA-b-CL)
      (48.1/51.9) P(LA-b-CL) (78.7/21.3) and PLGA microspheres, respectively) was
      reached at the second day post administration. And then P(LA-b-CL) microspheres
      showed a constant CyA level (about 100-200 ng ml(-1)) for extended periods of
      time (several weeks). Such CyA-loaded P(LA-b-CL) microspheres displaying higher
      CyA concentration during the first few days and similar constant blood CyA level
      thereafter showed more advantages than those prepared with PLGA and could meet
      clinical needs more efficiently.

PMID- 15847993
TI  - Grafted thermo- and pH responsive co-polymers: surface-properties and bacterial
      adsorption.
AB  - A series of responsive polymers displaying pH and temperature-mediated phase
      changes were prepared from N-isopropylacrylamide and omega-carboxylic acid
      functionalised acrylamides. These polymers were grafted to surfaces and their
      characteristics probed by atomic force microscopy in aqueous solutions. The
      effects of pH and temperature induced phase transitions on the short-term
      adsorption of the bacteria Salmonella typhimurium and Bacillus cereus from pure
      cultures were assessed. Contact angle studies indicated that pH and temperature
      dependent surface properties were exhibited by the graft polymer surfaces.
      Temperature-dependent surface morphology changes occurred through polymer graft
      phase transitions as observed in AFM and accompanying changes in adhesion forces
      underwater were found to correlate with surface properties obtained from contact
      angle measurements. Adsorption of S. typhimurium and B. cereus was not
      significantly altered as a function of pH, but attachment of both bacterial
      strains increased at temperatures above the polymer coil-globule transition
      indicating the importance of switching surface hydrophobicity in controlling
      short-term bacterial adsorption.

PMID- 15847994
TI  - In vitro characterization of some biopharmaceutical properties of praziquantel.
AB  - In several studies of patients with neurocysticercosis under treatment with
      praziquantel (PZQ), the pharmacokinetic data were difficult to interpret probably
      because of the low solubility as well as its variable oral bioavailability.
      Because there is limited information available regarding the biopharmaceutical
      properties of PZQ, the aim of this work was to evaluate the absorption
      characteristics of the drug and its dissolution behaviour in simulated media.
      Additionally, its in vitro protein binding and displacement by highly bound drugs
      was evaluated. Permeability evaluation was carried out by using Caco-2 cells.
      Dissolution release profiles were evaluated using the USP apparatus and the
      following dissolution media: HCl containing 2mg of sodium laurylsulfate per
      milliliter, milk, FeSSIF and FaSSIF. Protein binding of PZQ was carried out by
      equilibrium dialysis. Results showed that praziquantel was absorbed by passive
      diffusion. The apparent permeability constant value was 4.4x10(-5) cm/s. Binding
      was not influenced by the addition of highly bound drugs. Dissolution from a
      tablet formulation showed that the rate of praziquantel was dependent on the
      components of the media. Although the simulated media could explain the influence
      of the lipids on praziquantel absorption, they were not able to forecast the
      influence of carbohydrates. Further refinements are required to explain the in
      vivo data.

PMID- 15847995
TI  - Topical drug classification.
AB  - Current definitions of lotions, gels, creams and ointments vary depending on
      literature source, market history or traditional use. This often leads to
      confusion when deciding which dosage form to prescribe and/or purchase. The
      existing classification of topical dosage forms needs to be re-examined to ensure
      that definitions for different dosage forms are based on consistent scientific
      principles and that dosage forms can be distinguished from one another. The
      purpose of this study is to obtain a scientifically based, systematic
      classification of dosage forms for topical drugs. A variety of prescription and
      over-the-counter topical products currently marketed as lotions, gels, creams,
      and ointments are evaluated using different techniques including rheology
      (viscosity and shear rate versus shear stress), loss on drying (LOD), specific
      gravity, surface tension, thermogravimetric analysis (TGA), water absorption,
      dilution properties, microscopic evaluation, transmittance of visible light,
      appearance and composition. Rheology is the most discriminating property
      separating creams and lotions. Water plus volatiles (as measured by LOD) and
      composition separate ointments and creams. Composition and thermal behavior
      separate gels from the other dosage forms. Based on these findings, new
      definitions and a decision tree are presented to assist in the determination of
      the appropriate nomenclature for a topical dosage form.

PMID- 15847996
TI  - Nebulised gentamicin-suitable for childhood bronchiectasis.
AB  - Nebulised antibiotic therapy is an established, safe and effective therapy for
      cystic fibrosis with chronic pseudomonas infection resulting in improved
      pulmonary function and reduced hospitalisation. Despite similar respiratory
      disease, this therapy has not been evaluated in children with non cystic fibrosis
      bronchiectasis. This study evaluates the suitability of a gentamicin solution and
      nebuliser combination for use in this population. MATERIALS AND METHODS: Four
      millilitres of gentamicin (80 mg) in saline delivered by a PARI LC plus nebuliser
      and PARI Turboboy N compressor was used. The pH, osmolarity, chloride
      concentration and aerosol particle size was determined. Ten children with non
      cystic fibrosis bronchiectasis received nebulised antibiotic and had peak
      gentamicin concentrations measured in sputum and serum. Pulmonary function was
      measured pre and post nebulisation. RESULTS: The solution had an osmolarity of
      199 mOsm/l, pH of 4.1, chloride concentration of 75 mmol/l and the aerosol a mass
      median aerodynamic diameter of 3.3 microm. Nebulisation was well tolerated, with
      no significant change in FEV1. Peak serum levels were at the threshold of
      detectability (0.3 mg/l). Sputum concentrations had a mean of 624 mg/g and lower
      95th confidence interval 25 times the minimum inhibitory concentration for the
      predominant infecting organism, Haemophilus influenzae. CONCLUSION: Nebulisation
      of 80 mg of gentamicin in saline achieved bactericidal concentrations in sputum,
      was well tolerated and had negligible systemic absorption making it a suitable
      choice for this population.

PMID- 15847997
TI  - Synthesis, hydrolysis, and intraocular pressure lowering effects of fadolmidine
      prodrugs.
AB  - The objective of this study was to synthesize and evaluate various esters of
      fadolmidine, a novel alpha2-adrenergic agonist, as potential ophthalmic prodrugs.
      All studied prodrugs released the parent drug (i.e., fadolmidine) quantitatively
      via enzymatic hydrolysis in 80% human serum. The pivalyl ester was considered to
      be the most promising prodrug in this series, due to its good chemical stability
      (pH 5.0; 37 degrees C; t(1/2)=310 days) and optimal lipophilicity (logP(app)=1.8;
      1-octanol/phosphate buffer, pH 5.0), and was selected for further evaluation of
      its intraocular pressure (IOP) lowering effects in normotensive rabbits. The
      pivalyl ester showed increased IOP lowering ability when compared to an equimolar
      dose of fadolmidine, which was probably due to its increased lipophilicity and
      subsequent enhanced corneal penetration. The duration of action for the pivalyl
      ester was also longer than that of fadolmidine.

PMID- 15847998
TI  - Pharmacokinetic profiles of two tablet formulations of piroxicam.
AB  - There is considerable interest in developing new non-steroidal anti-inflammatory
      drugs (NSAIDs) formulations with faster onset of analgesic action like fast
      dissolving tablets. An open-label, randomized, single dose, crossover study with
      a 18 days washout period was conducted in 16 healthy volunteers to compare the
      pharmacokinetic profile of 20 mg piroxicam freeze-dried tablet (Proxalyoc,
      Cephalon) with that of 20 mg piroxicam capsule (Feldene, Pfizer). T(lag) with
      freeze-dried tablet was three times shorter than with capsule (21.6 min versus
      59.4 min). Mean AUC(0-30 min), mean AUC(0-1 h), mean plasma concentrations at 15
      min, 30 min and 1 h post-dose were significantly higher with the freeze-dried
      tablet than with the capsule, indicating that piroxicam was more rapidly absorbed
      from the freeze-dried tablet with higher plasma concentrations achieved at
      shorter intervals after dosing. The 90% confidence intervals of the ratios of
      means C(max), AUC(0-t), AUC(0-infinity) and T(1/2) all fell within the acceptance
      range of 0.8-1.25, demonstrating the bioequivalence of the two formulations.
      Although the bioavailability of the two formulations was similar, the
      administration of piroxicam as a freeze-dried tablet gave a much faster
      absorption rate during the first hour after dosing than the capsule formulation.
      This faster absorption is an obvious advantage for the treatment of acute
      episodes of pain.

PMID- 15847999
TI  - QSPR modeling of pseudoternary microemulsions formulated employing lecithin
      surfactants: application of data mining, molecular and statistical modeling.
AB  - Data mining, computer aided molecular modeling, descriptor calculation, genetic
      algorithm and multiple linear regression analysis techniques were combined
      together to generate predictive quantitative structure property relationship
      (QSPR) models explaining the formation of lecithin-based W/O microemulsions.
      Ninety-four microemulsion phase diagrams were collected from five different
      references published over the past few years. Computer-based molecular modeling
      techniques were then applied on the components of the collected microemulsion
      systems to generate corresponding plausible three-dimensional (3D) structures.
      The resulting 3D models were utilized to calculate a group of molecular
      physicochemical descriptors. Thereafter, genetic algorithm and backward stepwise
      regression analysis were separately assessed as means for selecting optimal
      descriptor sets for statistical modeling. The selected descriptors were
      correlated with microemulsion existence areas employing multiple linear
      regression analysis. The resulting W/O models were statistically validated and
      found to be of significant predictive power. The models allowed better
      understanding of the process of microemulsion formation. Unfortunately, all QSPR
      modeling efforts directed towards O/W microemulsions failed completely.

PMID- 15848000
TI  - Improvement of antischistosomal activity of praziquantel by incorporation into
      phosphatidylcholine-containing liposomes.
AB  - Praziquantel (PZQ) is effective against all known species of Schistosomes that
      infect humans. The failure of mass treatment of schistosomiasis has been
      attributed to the fact that therapy is not sufficiently long-lasting. This effect
      may be due to the low bioavailability of PZQ that has a low hydrosolubility and
      fast metabolism. Liposomes have been used to prolong drug levels, reduce the side
      effects, direct drugs to specific sites and increase bioavailability after
      administration. The aim of this work was to study the effect of
      phosphatidylcholine (PC)-containing liposomes to vehiculate PZQ to improve the
      treatment of schistosomiasis. The in vitro study was carried out using
      Schistosoma mansoni parasites recovered by perfusion from the hepatic portal
      system of infected mice. Suspensions of liposomes with PZQ and free PZQ were
      administered p.o. in mice after 14 days of infection. The effect of both
      preparations in vitro on S. mansoni culture was similar. In the in vivo test, PZQ
      liposomes caused a decrease in amounts of eggs and parasites. Liposomes improve
      the antischistosomal activity of praziquantel. This can be used as a starting
      point to investigate alternative administration routes or dosage forms and to
      examine the mechanism of intestinal absorption of PRZ.

PMID- 15848001
TI  - A rapid screening tool for estimating the potential of 2-hydroxypropyl-beta
      cyclodextrin complexation for solubilization purposes.
AB  - Quantitative structure-property relationships (QSPRs) were developed for
      predicting the solubility enhancement (expressed as logS/S0) of compounds in 45%
      (w/v) aqueous solution of HP-beta-CD. A set of 25 structurally different drugs,
      whose logS/S0 values were taken from literature, was used as a training set for
      building the computational models. Thirteen molecular descriptors, including
      parameters for size, lipophilicity, cohesive energy density and hydrogen-bonding
      capacity, were calculated and together with the experimental melting point (MP),
      used in multivariate analysis. Eight pertinent variables were detected after
      looking at the results of principal component analysis (PCA) and cluster
      analysis, and two reliable four-descriptor models generated by multiple linear
      regression (MLR) and by the partial least squares-projection to latent structures
      (PLS) methods. In both cases, satisfactory coefficients of determination values
      were obtained (i.e., R2 equal to 0.793 or 0.763 for MLR and PLS, respectively).
      The models were validated using a test set of six compounds. The equations
      generated can predict the aqueous solubility increase of poorly soluble compounds
      by complexation in 45% (w/v) aqueous solution of HP-beta-CD with a reasonable
      accuracy. These equations can allow formulation scientists to rapidly estimate,
      at the early stage of drug development, the potential of HP-beta-CD in increasing
      solubility of poorly water-soluble drugs.

PMID- 15848002
TI  - On the mechanism of solubilization of drugs in the presence of poorly soluble
      additives.
AB  - A model is proposed which describes the solubilization of a poorly soluble drug
      in the presence of an insoluble excipient which forms an easily soluble compound
      with the drug. For sulfathiazole-calcium carbonate system as an example, it is
      demonstrated using sulfathiazole single crystals and powdered samples that the
      presence of insoluble additive causes an increase in dissolution rate and
      solubility of the drug.

PMID- 15848003
TI  - Controlled delivery of testosterone from smart polymer solution based systems: in
      vitro evaluation.
AB  - The objective of this research is to develop injectable polymers solution based
      controlled release delivery systems for testosterone (TSN), using phase sensitive
      and thermosensitive polymers. A combination of poly(lactide) (PLA) and solvents
      mixture of benzyl benzoate (BB) and benzyl alcohol (BA) was used in the phase
      sensitive polymer delivery system. The effects of solvents system and drug
      loading on the in vitro TSN release were evaluated. In the case of
      thermosensitive polymer delivery systems, a series of low-molecular-weight
      poly(lactide-co-glycolide)-poly(ethylene glycol)-poly(lactide-co-glycolide) (PLGA
      PEG-PLGA) triblock copolymers with varying ratio of lactide/glycolide (LA/GA, 2.0
      3.5) were studied to control the release of TSN. The effects of varying block
      length of copolymers 1-4 on the in vitro TSN release were evaluated. Phosphate
      buffer saline (pH 7.4) containing 0.5% (w/v) Tween-80 was used as in vitro
      release medium. The amount of the released TSN was determined by an HPLC method.
      A controlled (zero-order) in vitro release of TSN was observed from both the
      phase sensitive and thermosensitive polymer delivery systems. Addition of BA
      (15%, v/v) in solvents system significantly (p<0.05) increased the release rate
      of TSN (0.33+/-0.01 mg/ml) from phase sensitive delivery system in comparison to
      solvent without BA (0.27+/-0.00 mg/day). Increasing drug loading also increased
      release rate. In the case of thermosensitive polymer delivery system, increasing
      the hydrophobic PLGA block length of copolymers significantly (p<0.05) decreased
      the release rate of TSN. It is evident from this study that the phase sensitive
      and thermosensitive polymers are suitable for developing prolong-release
      injectable implant delivery systems for TSN.

PMID- 15848004
TI  - An improved thermoanalytical approach to quantifying trace levels of polymorphic
      impurity in drug powders.
AB  - Accurate quantification of impurities existing as separate crystalline phases at
      trace levels in drug materials is an important issue in the pharmaceutical
      industry. In the present study, a thermoanalytical approach previously developed
      for quantifying trace levels of polymorphic impurity (form II metastable nuclei)
      in commercial salmeterol xinafoate powders has been successfully applied with
      slight modifications to ribavirin, an antiviral drug exhibiting roughly similar
      polymorph-dependent crystallization kinetics in melts to that of salmeterol
      xinafoate. Essentially, the approach involved modeling of the crystallization
      kinetics of both tested and reference drug materials in melts using the Avrami
      Erofe'ev (AE) rate expression, derivation of a mathematical equation for relating
      the AE kinetic constant to the composition of reference polymorph mixtures, and
      the use of this derived equation (in the form of a calibration curve) to
      calculate the impurity contents of the tested samples from their computed AE
      constants. For ribavirin, modification of the latter equation by incorporation of
      an empirical exponent was found necessary to account for the composition
      dependent changes in crystallization kinetics of the reference mixtures. Such
      modification has made possible the determination of polymorphic impurity content
      of as low as 0.004% (w/w) in ribavirin samples induced by different forms of
      grinding treatment.

PMID- 15848005
TI  - Nimesulide PLA microspheres as a potential sustained release system for the
      treatment of inflammatory diseases.
AB  - Polylactic acid (PLA-L) microspheres were prepared as a biodegradable polymeric
      carrier for a non-steroidal anti-inflammatory drug, nimesulide. The preparation
      of this system was performed by the classical emulsion solvent-evaporation
      method. Size analysis of the microparticulate system showed that unloaded and
      loaded nimesulide-PLA microspheres had average diameters of about 42.9 nm and 2.1
      microm, respectively. Scanning electron microscopy (SEM) of loaded and unloaded
      microsphere samples showed that the particles shape were perfectly spherical, the
      loading efficiency of nimesulide in PLA microspheres was 70%; Thus, the
      microparticle system evaluated in this work showed the potential to act as a
      sustained release system for nimesulide: in vitro dissolution profiles showed the
      PLA-L microparticles were able to sustain the release of the drug for a
      considerable period of time (28.7% within 108 h).

PMID- 15848006
TI  - Quantitation of active pharmaceutical ingredients and excipients in powder blends
      using designed multivariate calibration models by near-infrared spectroscopy.
AB  - This research note demonstrates the simultaneous quantitation of a pharmaceutical
      active ingredient and three excipients in a simulated powder blend containing
      acetaminophen, Prosolv and Crospovidone. An experimental design approach was used
      in generating a 5-level (%, w/w) calibration sample set that included 125
      samples. The samples were prepared by weighing suitable amount of powders into
      separate 20-mL scintillation vials and were mixed manually. Partial least squares
      (PLS) regression was used in calibration model development. The models generated
      accurate results for quantitation of Crospovidone (at 5%, w/w) and magnesium
      stearate (at 0.5%, w/w). Further testing of the models demonstrated that the 2
      level models were as effective as the 5-level ones, which reduced the calibration
      sample number to 50. The models had a small bias for quantitation of
      acetaminophen (at 30%, w/w) and Prosolv (at 64.5%, w/w) in the blend. The
      implication of the bias is discussed.

PMID- 15848007
TI  - Glycodendrimeric nanoparticulate carriers of primaquine phosphate for liver
      targeting.
AB  - In the present study it was intended to deliver primaquine phosphate (PP), a
      liver schizonticide directly to liver cells using polypropyleneimine (PPI)
      dendrimers-coated peripherally with galactose. PPI dendrimers were synthesized by
      consecutive Michael double addition reaction (using ethyelenediamine as core),
      followed by hydrogenation reaction. Galactose conjugation was carried out by ring
      opening reactions, followed by Schiff's reaction and reduction to secondary amine
      in sodium acetate buffer (pH 4.0). IR, NMR, MASS spectroscopy were used for the
      confirmation of synthesis of uncoated and coated dendrimers. The formulations
      were made by equilibrium dialysis of dendrimers with the solution of PP. Then the
      formulations were characterized by TEM for size and shape. Release rate,
      hemolytic toxicity; bio-distribution and blood level studies were also performed
      on lyophilized formulations. The results obtained indicated that galactose
      coating of PPI systems increases the drug entrapment efficiency by 5-15 times
      depending upon generations. Galactose coating prolonged release up to 5-6 days as
      compared to 1-2 days for uncoated PPI systems. The hemolytic toxicity, blood
      level and hematological studies proved these systems to be safer and suitable for
      sustained drug delivery. Blood level studies proved the suitability of the
      systems for the prolonged circulations and delivery of PP to liver. The galactose
      coating of PPI dendrimers can therefore make the PPI systems more effective and
      suitable for targeted delivery of Primaquine phosphate to liver.

PMID- 15848008
TI  - Chitosan nanoparticles as a novel delivery system for ammonium glycyrrhizinate.
AB  - The ammonium glycyrrhizinate-loaded chitosan nanoparticles were prepared by ionic
      gelation of chitosan with tripolyphosphate anions (TPP). The particle size and
      zeta potential of nanoparticles were determined, respectively, by dynamic light
      scattering (DLS) and a zeta potential analyzer. The effects, including chitosan
      molecular weight, chitosan concentration, ammonium glycyrrhizinate concentration
      and polyethylene glycol (PEG) on the physicochemical properties of the
      nanoparticles were studied. These nanoparticles have ammonium glycyrrhizinate
      loading efficiency. The encapsulation efficiency decreased with the increase of
      ammonium glycyrrhizinate concentration and chitosan concentration. The
      introduction of PEG can decrease significantly the positive charge of particle
      surface. These studies showed that chitosan can complex TPP to form stable
      cationic nanoparticles for subsequent ammonium glycyrrhizinate loading.

PMID- 15848009
TI  - Cationic albumin conjugated pegylated nanoparticle with its transcytosis ability
      and little toxicity against blood-brain barrier.
AB  - Our newly developed drug delivery carrier, cationic bovine serum albumin (CBSA)
      conjugated with poly(ethyleneglycol)-poly(lactide) (PEG-PLA) nanoparticle (CBSA
      NP), was designed for brain drug delivery. CBSA, as a brain specific targetor,
      was covalently conjugated with the maleimide function group at the distal of
      poly(ethyleneglycol) (PEG) surrounding the nanoparticles. To evaluate its blood
      brain barrier (BBB) transcytosis and toxicity against the BBB endothelial tight
      junction, we have explored a method of coculture with brain capillary endothelial
      cells (BCECs) on the top of micro-porous membrane of cell culture insert and
      astrocytes on the bottom side. The permeability of 14C-labeled sucrose was
      determined. For the CBSA-NP transcytosis study, a lipophilic fluorescent probe, 6
      coumarin, was incorporated into nanoparticles. The BBB permeability of CBSA-NP in
      vitro was calculated and compared with native bovine serum albumin (BSA)
      conjugated pegylated nanoparticles (BSA-NP). As the coculture model, the
      transendothelial electrical resistance reached up to 313+/-23 ohms cm2. The tight
      junction between BCECs in the coculture could be visualized by scanning electron
      microscopy and transmission electron microscopy. The unchanged permeability of
      14C-labeled sucrose comparing to that in the appearance of 200 microg/ml of CBSA
      NP proved that CBSA-NP did not impact the integrity of BBB endothelial tight
      junctions. CBSA-NP also showed little toxicity against BCECs. The permeability of
      CBSA-NP was about 7.76 times higher than that of BSA-NP, while the transcytosis
      was inhibited in the excess of free CBSA. It was concluded that CBSA-NP
      preferentially transported across BBB with little toxicity, which offered the
      possibility to deliver therapeutic agents to CNS.

PMID- 15848010
TI  - Preparation and characterization of n-dodecyl-ferulate-loaded solid lipid
      nanoparticles (SLN).
AB  - Solid lipid nanoparticles (SLN) containing a novel potential sunscreen n-dodecyl
      ferulate (ester of ferulic acid) were developed. The preparation and stability
      parameters of n-dodecyl-ferulate-loaded SLN have been investigated concerning
      particle size, surface electrical charge (zeta potential) and matrix
      crystallinity. The chemical stability of n-dodecyl-ferulate at high temperatures
      was also assessed by thermal gravimetry analysis. For the selection of the
      appropriated lipid matrix, chemically different lipids were melted with 4% (m/m)
      of active and lipid nanoparticles were prepared by the so-called high pressure
      homogenization technique. n-Dodecyl-ferulate-loaded SLN prepared with cetyl
      palmitate showed the lowest mean particle size and polydispersity index, as well
      as the highest physical stability during storage time of 21 days at 4, 20 and 40
      degrees C. These colloidal dispersions containing the sunscreen also exhibited
      the common melting behaviour of aqueous SLN dispersions.

PMID- 15848011
TI  - Effect of nanoprecipitation on the physicochemical properties of low molecular
      weight poly(L-lactic acid) nanoparticles loaded with salbutamol sulphate and
      beclomethasone dipropionate.
AB  - A modified nanoprecipitation (interfacial polymer deposition following solvent
      displacement) method was used to produce nanoparticles from low molecular weight
      poly(L-lactic acid). Model drugs, either salbutamol sulphate or beclomethasone
      dipropionate, were encapsulated in the particles. The influence of the
      preparation method on the physicochemical state of the polymer and the drugs as
      well as on the drug-polymer interactions were studied by electron microscopy, X
      ray diffractometry, thermal analysis and infrared spectroscopy. Nanoprecipitation
      lowered the crystallinity of the PLA polymer. The crystallinity of the polymer
      was higher in the particles containing salbutamol sulphate then those containing
      beclomethasone dipropionate. The crystal form of beclomethasone dipropionate was
      changed from an anhydrate to a monohydrate as a result of nanoprecipitation.
      Although changes in the crystallinity of the polymer and the model drugs were
      seen, no clear interactions between the polymer and the drug were detected.

PMID- 15848012
TI  - An ethnobotanical survey of Bauchi State herbal plants and their antimicrobial
      activity.
AB  - A survey of medicinal plants used locally in the treatment of various diseases
      was carried out in Bauchi State-Nigeria. A total of 84 medicinal plants were
      listed. Preliminary antimicrobial activity of the aqueous extracts of the plants
      was investigated. The results indicated that out of 84 plants, 75 exhibited
      antimicrobial activity against one or more of the test organisms at a
      concentration of 200 mg/ml. The extracts were found to show potentially
      interesting activity against Proteus mirabilis, Pseudomonas aeruginosa,
      Staphylococcus aureus and Escherichia coli.

PMID- 15848013
TI  - Effects of propolis on cell growth and gene expression in HL-60 cells.
AB  - Brazilian propolis obtained from honeybee hives was extracted with water or
      ethanol. Cell growth-inhibitory activities of these propolis extracts were found
      in HL-60 human myeloid leukemia cells. The extracts-induced apoptosis in the
      cells, which was characterized by morphological and nucleosomal DNA fragmentation
      analysis. The apoptosis was mainly attributed to the induction of granulocytic
      differentiation, which was evaluated by nitro blue tetrazolium (NBT) reducing
      assays and cytofluorometric analysis for the expression of cell surface marker
      CD11b. DNA microarray analysis was performed to examine the gene expression
      profiles in the propolis-treated HL-60 cells accompanied with granulocytic
      differentiation, which were compared with those in all-trans retinoic acid
      treated cells. Several genes were up- or down-regulated. Two genes encoding S100
      calcium binding protein A9 and ferritin, heavy polypeptide 1 were up-regulated,
      which were also confirmed by semi-quantitative reverse transcriptase-PCR (RT
      PCR). Propolis-induced growth inhibition in HL-60 cells was, at least in part,
      due to differentiation with gene expression profiles, which are similar to those
      induced by all-trans retinoic acid.

PMID- 15848014
TI  - Antinociceptive, anti-inflammatory and antidiabetic effects of Bryophyllum
      pinnatum (Crassulaceae) leaf aqueous extract.
AB  - In order to scientifically appraise some of the ethnomedical uses of Bryophyllum
      pinnatum leaves, the present study was undertaken to investigate the
      antinociceptive, anti-inflammatory and antidiabetic properties of the plant's
      leaf aqueous extract in experimental animal models. The antinociceptive effect of
      the herb's leaf extract was evaluated by the 'hot-plate' and 'acetic acid' test
      models of pain in mice. The anti-inflammatory and antidiabetic effects of the
      plant's extract were investigated in rats, using fresh egg albumin-induced pedal
      (paw) oedema, and streptozotocin (STZ)-induced diabetes mellitus. Diclofenac
      (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used respectively as
      reference drugs for comparison. Bryophyllum pinnatum leaf aqueous extract (BPE,
      25-800 mg/kg i.p.) produced significant (P<0.05-0.001) antinociceptive effects
      against thermally- and chemically-induced nociceptive pain stimuli in mice. The
      plant extract (BPE, 25-800 mg/kg p.o. or i.p.) also significantly (P<0.05-0.001)
      inhibited fresh egg albumin-induced acute inflammation and caused significant
      (P<0.05-0.001) hypoglycaemia in rats. The results of this experimental animal
      study suggest that Bryophyllum pinnatum leaf aqueous extract possesses
      antinociceptive, anti-inflammatory and hypoglycaemic properties. The different
      flavonoids, polyphenols, triterpenoids and other chemical constituents of the
      herb are speculated to account for the observed antinociceptive, anti
      inflammatory and antidiabetic properties of the plant.

PMID- 15848015
TI  - Studies of the anticancer potential of plants used in Bangladeshi folk medicine.
AB  - The present study evaluated the anticancer potential of 11 plants used in
      Bangladeshi folk medicine. The extracts were tested for cytotoxicity using the
      brine shrimp lethality assay, sea urchin eggs assay, hemolysis assay and MTT
      assay using tumor cell lines. The extract of Oroxylum indicum showed the highest
      toxicity on all tumor cell lines tested, with an IC(50) of 19.6 microg/ml for
      CEM, 14.2 microg/ml for HL-60, 17.2 microg/ml for B-16 and 32.5 microg/ml for HCT
      8. On the sea urchin eggs, it inhibited the progression of cell cycle since the
      frist cleavage (IC(50)=13.5 microg/ml). The extract of Aegle marmelos exhibited
      toxicity on all used assays, but in a lower potency than Oroxylum indicum. In
      conclusion, among all tested extracts, only the extracts of Oroxylum indicum,
      Moringa oleifera and Aegles marmelos could be considered as potential sources of
      anticancer compounds. Further studies are necessary for chemical characterization
      of the active principles and more extensive biological evaluations.

PMID- 15848016
TI  - Acute diuretic effect of aqueous extract of Retama raetam in normal rats.
AB  - The purpose of this study was to examine the acute diuretic effect of the water
      extract of the aerial parts of Retama raetam (RR) at a dose of 5 mg/kg/h in
      normal rats. The aqueous extract was administered intravenously and the diuresis
      was followed within 4 h after starting the treatment. Intravenous administration
      of the aqueous RR extract produced a significant increment on diuresis from the
      second hour (p<0.01) to the fourth hour (p<0.001). Furosemide at a dose of 0.1
      mg/kg/h had a similar effect when compared to RR administration. Parallel, the
      noticed increase of diuresis was associated with an elevation of glomerular
      filtration rate (p<0.05) and a significant decrease of urinary osmolarity
      (p<0.001). However, RR extract did not affect plasma urea levels, urine pH,
      plasma osmolarity and hematocrite. It is then concluded that the water extract of
      the aerial parts of RR exhibited a significant diuretic effect in normal rat.

PMID- 15848017
TI  - Down-modulation of nitric oxide production in murine macrophages treated with
      crude plant extracts from the Brazilian Cerrado.
AB  - Several plant species from the Cerrado biome in Brazil are popularly used as
      herbal medicines for its reputed analgesic, anti-acid, anti-microbial, anti
      inflammatory and anti-tumoral properties, among others. It has been reported that
      some plant extracts interfere in the production of nitric oxide (NO), an
      important inflammatory mediator. In the present study, we investigated the effect
      of hexanic and ethanolic extracts from three plant species on NO production by
      LPS/IFN-gamma-activated J774 macrophages based on traditional use. The cytotoxic
      effect of the crude extracts was determined by the thiazolyl blue test (MTT) to
      measure cell viability. Serjania lethalis stem extracts and Cupania vernalis leaf
      extracts significantly inhibited NO production, while extracts from Casearia
      sylvestris var. lingua were inactive or showed low activity on NO production, or
      were very cytotoxic. The ethanolic stem bark and leaf extracts of Serjania
      lethalis and Cupania vernalis, respectively, almost completely inhibited the
      production of NO by J774 macrophages. It can be concluded that the selected
      extracts are potential sources of active compounds that might be used as anti
      inflammatory agents.

PMID- 15848018
TI  - Antioxidant activity and cytotoxicity of eight plants used in traditional Arab
      medicine in Israel.
AB  - Ethnopharmacological surveys conducted among herbal practitioners of traditional
      Arab medicine in Israel and the Palestinian area have revealed a large number of
      indigenous plant species are used as sources of their herbal therapies. Some of
      these herbal therapies are used to treat liver disease, jaundice or diabetes,
      conditions in which oxidative stress is prominent. No laboratory data on the
      bioactivity of herbal medicines in these settings exist in traditional Arab
      medicine. We hypothesized that the beneficial effect of these plants might be due
      to their antioxidant properties. Accordingly, we selected eight plants used to
      treat these two conditions and assessed their antioxidant potential by measuring
      their ability to suppress the extent of iron-induced lipid peroxidation in rat
      liver homogenates and their potential toxicity by evaluating their effects on
      mitochondrial respiration and cell membrane integrity in cultured PC12 and HepG2
      cells. We found that all the extracts can suppress iron-induced lipid
      peroxidation and are not toxic. Of these extracts, those prepared from Teucrium
      polium and Pistacia lentiscus were the most effective in suppressing iron-induced
      lipid peroxidation. Further investigations are now needed to establish the exact
      mechanism of action and identify the active bio-ingredient(s) of each extract in
      order to explain their therapeutic efficacy.

PMID- 15848019
TI  - Fraxinus excelsior L. evokes a hypotensive action in normal and spontaneously
      hypertensive rats.
AB  - The hypotensive effect of an aqueous extract of Fraxinus excelsior L. was
      investigated in both normotensive (WKY) and spontaneously hypertensive rats
      (SHR). Daily oral administration of Fraxinus excelsior (20 mg/kg) aqueous extract
      for 3 weeks produced a significant decrease in systolic blood pressure (SBP) with
      variation coefficient (Delta%) of 13.5% in SHR (p<0.01) and 9% in WKY rats
      (p<0.05). The aqueous extract of Fraxinus excelsior significantly enhanced the
      urination in both SHR (p<0.05 compared to control) and WKY (p<0.05 compared to
      control). Irbesartan (Avapro), an angiotensin II antagonist, was used as
      reference drug. Furthermore, oral administration of aqueous Fraxinus excelsior
      extract at a dose of 20 mg/kg produced a significant increase in urinary
      excretion of sodium (p<0.01 compared to control), potassium (p<0.001 compared to
      control) and chlorides (p<0.01) in SHR rats. In normal rats, the aqueous Fraxinus
      excelsior extract administration induced a significant increase of the urinary
      elimination of sodium (p<0.05 compared to control), chlorides (p<0.01 compared to
      control) and potassium (p<0.01 versus control). While there were no significant
      changes in heart rate (HR) after Fraxinus excelsior treatment in both SHR and WKY
      rats, glomerular filtration rate (GFR) showed a significant increase in SH rats
      (p<0.001) after Fraxinus excelsior treatment. These results suggest that oral
      administration of aqueous extract of Fraxinus excelsior exhibited hypotensive and
      diuretic actions.

PMID- 15848020
TI  - Preventive effect of Abelmoschus manihot (L.) Medik. on bone loss in the
      ovariectomised rats.
AB  - Because the biggest culprit in pathogenesis of osteoporosis is oestrogen
      deficiency, hormone replacement therapy remained the mainstay for prevention.
      However most of postmenopausal women are more inclined to use natural
      alternative. We thus investigated the ability of Abelmoschus manihot, a herbal
      medicine to prevent bone loss in ovariectomised rats. Female Wistar rats were
      sham operated (SH: 8) or ovariectomised (OVX: 24). On day 0, OVX rats were
      randomly assigned to groups as follows: eight received 10% Abelmoschus manihot
      leaves in their diet, eight were given 15% Abelmoschus manihot leaves and eight
      were untreated (OVX). Compounds were mixed with a soy protein-free diet and given
      orally for 3 months. At necropsy, bone mineral density (BMD) in the femur and in
      its metaphyseal zone was lower in OVX than SH (p<0.05). This osteopenia was
      prevented by consumption of the highest dose of Abelmoschus manihot leaves. Bone
      mineral content (BMC) in the total femur and its metaphyseal and diaphyseal
      subregions was improved, as well (p<0.05). This could be explained by a trend
      towards decreased bone resorption. The lowest dose did not elicit any significant
      effect. In conclusion, Abelmoschus manihot consumption, at the dose of 15% in the
      diet, provided bone-sparing effects by improving both BMD and BMC.

PMID- 15848021
TI  - Influence of co-administrated sinomenine on pharmacokinetic fate of paeoniflorin
      in unrestrained conscious rats.
AB  - Paeonia lactiflora Pall. (Ranunculaceae) root and Sinomenium acutum Rehder and
      Wilson (Menispermaceae) stem are two herbs widely used in Chinese medicine to
      treat rheumatoid arthritis. While, in theory, either herb could be used alone, in
      practice, Chinese medicine practitioners prescribe them together. Studies on
      pharmacokinetic interaction between the active constituents of these two herbs
      (paeoniflorin and sinomenine, respectively) provide empirical evidence to support
      their clinical practice. A single dose of paeoniflorin (150 mg/kg) alone and with
      sinomenine hydrochloride (90 mg/kg) was administered by gastric gavage to
      unrestrained conscious male Sprague-Dawley rats (n=5 or 6, 240-270 [corrected]
      g). Blood samples were collected periodically via a jugular vein before and after
      dosing from 10 min to 12 h. A high-performance liquid chromatographic (HPLC)
      assay was developed to determine the plasma concentrations of paeoniflorin. Non
      compartmental pharmacokinetic profiles were constructed by using the software PK
      Solutions 2.0. The pharmacokinetic parameters were compared using unpaired
      Student t-test. After co-administration of sinomenine, the peak plasma
      concentration of paeoniflorin was elevated (P<0.01), the peak time was delayed
      (P<0.01), the AUC(0-t) was increased (P<0.001), the mean residence time (MRT) was
      prolonged (P<0.01), the C(L) was decreased (P<0.01) and the V(d) was reduced
      (P<0.05). These results indicate that sinomenine hydrochloride at 90 mg/kg
      significantly improved the bioavailability of paeoniflorin in rats.

PMID- 15848022
TI  - Chemical composition and antibacterial activity of propolis collected by three
      different races of honeybees in the same region.
AB  - The chemical analysis and antibacterial activity of three types of propolis
      collected three different races of Apis mellifera bee in the same apiary were
      investigated. Propolis samples were investigated by GC/MS, 48 compounds were
      identified 32 being new for propolis. The compounds identified indicated that the
      main plant sources of propolis were Populus alba, Populus tremuloides and Salix
      alba. The antimicrobial activity against Staphylococcus aureus, Escherichia coli,
      Pseudomonas aeruginosa and Candida albicans was evaluated. Ethanolic extracts of
      propolis samples showed high antibacterial activity against Gram-positive cocci
      (Staphylococcus aureus), but had a weak activity against Gram-negative bacteria
      (Escherichia coli and Pseudomonas aeruginosa) and yeast (Candida albicans).
      Propolis sample collected by Apis mellifera caucasica showed a higher
      antibacterial activity than collected by Apis mellifera anatolica and Apis
      mellifera carnica.

PMID- 15848023
TI  - Hypoglycemic and antidiabetic effect of ethanolic extract of leaves of Annona
      squamosa L. in experimental animals.
AB  - The ethanolic extract of Annona squamosa L. (Annonaceae) leaves was administered
      orally at different doses to normal as well as streptozotocin (STZ)-induced
      diabetic rats and alloxan-induced diabetic rabbits. The dose of 350 mg/kg body
      weight (bw) reduced the fasting blood glucose (FBG) level by 6.0% within 1 h,
      whereas, the peak blood glucose at 1 h during glucose tolerance test (GTT) was
      reduced by 17.1% in normal rats. The same dose of ethanolic extract reduced FBG
      by 26.8% and improved glucose tolerance by 38.5 and 40.6% at 1 and 2 h,
      respectively, during GTT in alloxan-induced diabetic rabbits. In STZ-diabetic
      rats, a fall of 13.0% in FBG and an improvement in glucose tolerance by 37.2 and
      60.6% at 1 and 2 h, respectively, was observed during GTT. The dose of 350 mg/kg
      bw of ethanolic extract in 10-day treatment of a group of STZ-diabetic rats
      produced 73.3% fall in FBG level and no sugar was observed in fasting urine.
      Treatment of severely-diabetic rabbits for 15 days with a dose of 350 mg/kg of
      extract reduce FBG by 52.7% and urine sugar by 75%. It brought about fall in the
      level of total cholesterol (TC) by 49.3% with increase of 30.3% in high-density
      lipoprotein (HDL) and decrease of 71.9 and 28.7% in low-density lipoprotein (LDL)
      and triglycerides (TG) levels, respectively.

PMID- 15848024
TI  - Evaluation of selected South African medicinal plants for inhibitory properties
      against human immunodeficiency virus type 1 reverse transcriptase and integrase.
AB  - Seventeen aqueous and methanol extracts from nine South African medicinal plants,
      ethnobotanically selected, were screened for inhibitory properties against HIV-1
      reverse transcriptase (RT). Isolated compounds were additionally evaluated on HIV
      1 integrase (IN). The strongest inhibition against the RNA-dependent-DNA
      polymerase (RDDP) activity of RT was observed with the methanol extract of the
      stem-bark of Peltophorum africanum Sond. (Fabaceae) (IC(50) 3.5 microg/ml), while
      the methanol extract of the roots of Combretum molle R.Br. ex G. Don
      (Combretaceae) was the most inhibitory on the ribonuclease H (RNase H) activity
      (IC(50) 9.7 microg/ml). The known compounds bergenin and catechin, and a red
      coloured gallotannin composed of meta-depside chains of gallic and protocatechuic
      acids esterified to a 1-O-isobutyroly-beta-D-glucopyranose core, were isolated
      from the methanol extract of the roots and stem-bark of Peltophorum africanum.
      The gallotannin inhibited the RDDP and RNase H functions of RT with IC(50) values
      of 6.0 and 5.0 microM, respectively, and abolished the 3'-end processing activity
      of IN at 100 microM. Catechin showed no effect on RT but had a moderate activity
      on HIV-1 IN. Bergenin was inactive on both enzymes. The aqueous and methanol
      extracts were non-toxic in a HeLaP4 cell line at a concentration of 400
      microg/ml.

PMID- 15848025
TI  - Tanshinone: an inhibitor of proliferation of vascular smooth muscle cells.
AB  - Tanshinone (Tan) is one of the active components of Radix Salvia miltiorrhiza
      (Lamiaceae), which is clinically used to treat cardiovascular diseases in China.
      The aim of this study was to estimate the effect of Tan on the proliferation of
      cultured vascular smooth muscle cells (VSMCs) induced by fatal bovine serum
      (FBS). It was shown that various concentrations of Tan inhibited the VSMCs
      proliferation in a dose-dependent manner. Tan significantly blocked VSMCs cell
      cycle in G(0)/G(1) phase. The anti-proliferative effect of Tan was associated
      with the inhibition of the extracellular signal-regulated kinase1/2 (ERK1/2). On
      the other hand, the decrement of Tan on the cyclin D1 protein may be related to
      the high expression of p21(waf/cip1). The data suggest that the anti
      proliferative effect of Tan on VSMCs proliferation was associated with ERK1/2
      signaling pathway.

PMID- 15848026
TI  - Adjuvant effect of ethanol extract of Semen Cuscutae on the immune responses to
      ovalbumin in mice.
AB  - An ethanol extract of Semen Cuscutae (EESC) was evaluated for its adjuvant
      potentials on the cellular and humoral immune responses of ICR mice against
      ovalbumin (OVA). ICR mice were immunized subcutaneously with OVA 100 microg alone
      or with OVA 100 microg dissolved in saline containing aluminum hydroxide gel
      (Alum) (200 microg), Quil A (10 or 50 microg) or EESC (100, 200 or 400 microg) on
      Days 1 and 15. Two weeks later (Day 28), concanavalin A (Con A)-, pokeweed (PWM)-
      and OVA-stimulated splenocyte proliferation and OVA-specific antibody in serum
      were investigated. EESC significantly enhanced the Con A-, PWM-, and OVA-induced
      splenocyte proliferation in OVA-immunized mice at a dose of 200 microg (P<0.05 or
      P<0.025). OVA-specific IgG, IgG1 and IgG2b antibody levels in serum were
      significantly enhanced by EESC compared with OVA control group (P<0.025).
      Moreover, enhancing effects of EESC on these OVA-specific antibody responses to
      OVA in mice were more significant than those of Alum and Quil A (P<0.025). In
      conclusion, the results suggest that EESC is effective on Th1 and Th2 cell
      functions, and could be safely used as adjuvant.

PMID- 15848027
TI  - The sequences of the plastid gene rpl16 and the rpl16-rpl14 spacer region allow
      discrimination among six species of Scutellaria.
AB  - Dried aerial parts of Scutellaria galericulata L. (Labiatae; marsh skullcap) and
      Scutellaria lateriflora L. (Labiatae; mad dog skullcap) are mainly used as
      skullcap, a medicinal herb, in Europe and the United States. The respective dried
      aerial parts of the two species are difficult to distinguish morphologically from
      each other. We attempted to discriminate among six species (Scutellaria altissima
      L. (Labiatae), Scutellaria baicalensis Georgi (Labiatae), Scutellaria
      galericulata, Scutellaria incana Spreng. (Labiatae), Scutellaria indica L.
      (Labiatae) and Scutellaria lateriflora) of Scutellaria, which include three
      medicinal species (Scutellaria galericulata, Scutellaria lateriflora and
      Scutellaria baicalensis), by comparing the respective nucleotide sequences of the
      plastid rpl16 gene and the rpl16-rpl14 spacer region. Comparisons of these
      sequences allowed us to identify each of the six species unequivocally.

PMID- 15848028
TI  - Antioxidant activity of Siamese neem tree (VP1209).
AB  - Leaves, fruits, flowers and stem bark extracts from the Siamese neem tree
      (Azadirachta indica A. Juss var. siamensis Valeton, Meliaceae) were assessed for
      antioxidant activity in vitro using the 1,1-diphenyl-2-picryl hydrazyl (DPPH)
      scavenging assay, total antioxidant activity and inhibition of lipid peroxidation
      in Chago K1 cancer cell culture by the thiobarbituric acid reactive substances
      (TBARS) method. The results showed that leaf aqueous extract, flower and stem
      bark ethanol extracts exhibited higher free radical scavenging effect on the DPPH
      assay with 50% scavenging activity at 26.5, 27.9 and 30.6 microg/ml,
      respectively. The total antioxidant activity of these extracts was found to be
      0.959, 0.988 and 1.064 mM of standard trolox, respectively. At 100 microg/ml, the
      flower ethanol and leaf aqueous extracts significantly decreased malondialdehyde
      (MDA) levels (46.0 and 50.6%, respectively) by the TBARS method. The results
      suggest that extracts from leaf, flower and stem bark of the Siamese neem tree
      have strong antioxidant potential. This report supports the ethnomedical use of
      young leaves and flowers of this plant as a vegetable bitter tonic to promote
      good health.

PMID- 15848029
TI  - Screening of vasorelaxant activity of some medicinal plants used in Oriental
      medicines.
AB  - Hexane, ethylacetate (EtOAC), and n-butanol (n-BuOH) extracts of medicinal plants
      traditionally used in the East Asia, such as China, Korea, and Japan were
      screened for their vasorelaxant activity using isolated rat aorta. Among the 60
      solvent-extracts from 20 medicinal plants, hexane and n-BuOH extracts of
      Diospyros kaki and Polygonum aviculare, hexane, EtOAC, and n-BuOH extracts of
      Magnolia liliflora, n-BuOH extract of Sorbus commixta, and EtOAC and n-BuOH
      extracts of Selaginella tamariscina were found to exhibit distinctive
      vasorelaxant activity. The activity disappeared by removal of functional
      endothelium or pre-treatment of the aortic tissues with N(G)-nitro-L-arginine
      methyl ester (L-NAME), which is an inhibitor of nitric oxide synthase. These
      findings suggest that the medicinal plants relax vascular smooth muscle via
      endothelium-dependent nitric oxide. These results will be useful to further
      analyze those medicinal plants that contain the vasorelaxant activity in order to
      identify the active principles.

PMID- 15848030
TI  - Analgesic-antiinflammatory properties of Proustia pyrifolia.
AB  - The antiinflammatory (per os and topic) and analgesic (per os) properties of the
      aerial part of Proustia pyrifolia a species in danger of extinction were
      investigated, and the major compounds of two of its active extracts were
      isolated. In addition, the evaluation of cytotoxicity in three tumoral cell lines
      and the acute toxicity of the crude methanol extract were also assayed, together
      with the antioxidant activity for the different extracts of this species. The
      results of the evaluation of the topic antiinflammatory activities induced by
      arachidonic acid, and phorbol 12-myristate 13-acetate of the different extracts
      showed that this species possesses active constituents that could diminish cyclo
      oxygenase and lipoxygenases activities, the enzymes that allow the synthesis of
      proinflammatory endogenous substances as prostaglandin E(2) and leukotrienes,
      respectively. Our results corroborate the antiinflammatory and analgesic effects
      of Proustia pyrifolia, and could justify its use in folk medicine for the
      treatment of rheumatic and gout illnesses. From bio-active extracts beta
      sitosterol, quercetin and dihydroquercetin were obtained, and these compounds
      could explain in part the antiinflammatory, analgesic and antioxidant activities
      of this species. The crude methanol extract did not present acute toxicity or
      cytotoxic activity, however only this extract exhibited antioxidant activity.

PMID- 15848031
TI  - Antinociceptive activity of Calotropis procera latex in mice.
AB  - This work evaluated the antinociceptive effect of proteins from the Calotropis
      procera (Asclepiadaceae) latex using three different experimental models of
      nociception in mice. The latex protein fraction administered intraperitoneally in
      male mice at the doses of 12.5, 25 and 50 mg/kg showed the antinociceptive effect
      in a dose dependent manner compared to the respective controls in all assays.
      Inhibitions of the acetic acid-induced abdominal constrictions were observed at
      the doses of 12.5 (67.9%), 25 (85%) and 50 (99.5%) mg/kg compared to controls.
      Latex protein at the doses of 25 (39.8%; 42%) and 50 mg/kg (66.6%; 99.3%) reduced
      the nociception produced by formalin in the 1st and 2nd phases, respectively, and
      this effect was not reversed by pretreatment with naloxone (1 mg/kg). In the hot
      plate test, an increase of the reaction time was observed only at 60 min after
      the treatment with latex at the doses of 25 (79.5%) and 50 (76.9%) mg/kg,
      compared to controls and naloxone was ineffective to reverse the effect. It was
      concluded that the protein fraction derived from the whole latex of Calotropis
      procera possesses antinociceptive activity, which is independent of the opioid
      system.

PMID- 15848032
TI  - Effects of Nigella unguicularis fixed oil on blood biochemistry and
      oxidant/antioxidant balance in rats.
AB  - In the present study, Nigella unguicularis (Lam.) Spenner (Ranunculaceae) (Nu)
      fixed oil was administered orally to Wistar Kyoto rats for 4 weeks. The effects
      of the oil on serum lipid profile, haematological parameters and
      oxidant/antioxidant balance were investigated. The study showed that daily
      administration of the oil (1 ml/kg orally for 4 weeks) caused a significant
      decrease in serum total cholesterol, VLDL-cholesterol, triglycerides, glucose
      levels and a significant elevation of serum high-density lipoprotein level. The
      serum transaminases ( aspartate transaminase (AST), alanine transaminase (ALT)),
      alkaline phosphatase, bilirubin, blood urea nitrogen, urea, mean corpuscular
      haemoglobin concentration decreased significantly while albumin, mean corpuscular
      volume and fibrinogen levels increased significantly compared to control values.
      The administration of the oil (1 ml/kg orally for 4 weeks) caused a significant
      increase total antioxidant status in rats. Treatment with Nigella unguicularis
      oil did not effect malondialdehyde (MDA) concentrations. It is concluded that
      Nigella unguicularis oil possesses favourable metabolic effects on blood
      biochemistry and oxidant/antioxidant balance in rats.

PMID- 15848033
TI  - The in vitro and in vivo antimalarial activity of Cardiospermum halicacabum L.
      and Momordica foetida Schumch. Et Thonn.
AB  - Two plants Cardiospermum halicacabum L. and Momordica foetida Schumch. Et Thonn
      traditionally used to treat symptoms of malaria in parts of East and Central
      Africa were screened for in vitro and in vivo antimalarial activity. Using the
      nitro tetrazolium blue-based parasite lactate dehydrogenase assay as used by
      [Makler, M.T., Ries, J.M., Williams, J.A., Bancroft, J.E., Piper, R.C., Gibbins,
      B.L., Hinrichs, D.J., 1993. Parasite lactate dehydrogenase as an assay for
      Plasmodium falciparum drug sensitivity. American Journal of Tropical Medicine and
      Hygiene 48, 739-741], water extracts from the two plants were found to have weak
      in vitro antiplasmodial activity with 50% inhibitory concentrations (IC50s)
      greater than 28.00 microg/ml. In vivo studies of water extracts from the two
      plants showed that Momordica foetida given orally in the dose range 10, 100, 200
      and 500 mg/kg twice daily prolonged survival of Plasmodium berghei (Anka)
      infected mice from 7.0+/-1.8 to 17.9+/-1.8 days. The water extract of
      Cardiospermum halicacabum L was toxic to mice, none surviving beyond day 4 of
      oral administration, with no evidence of protection against Plasmodium berghei
      malaria. The study emphasizes the discrepancy that might be found between in
      vitro and in vivo testing of plant-derived antimalarial extracts and the need to
      consider in vitro antiplasmodial data with this in mind. Further studies on
      Momordica foetida as a source of an antimalarial remedy are indicated on the
      basis of these results.

PMID- 15848034
TI  - Two flavonoids from Artemisia herba-alba Asso with in vitro GABAA-benzodiazepine
      receptor activity.
AB  - An ethyl acetate extract of Artemisia herba-alba was partitioned by HPLC in 10
      fractions that were tested in the [(3)H]-flumazenil radioligand assay, for
      affinity to the GABA(A)-benzodiazepine receptor. Two fractions showed activity
      from which hispidulin and cirsilineol were isolated. The structures were
      confirmed by (1)H NMR. The IC(50) values were 8 microM for hispidulin and 100
      microM for cirsilineol.

PMID- 15848035
TI  - Antimicrobial activity of Curcuma zedoaria and Curcuma malabarica tubers.
AB  - The antimicrobial activity of extracts of Curcuma zedoaria and Curcuma malabarica
      tubers was tested against six bacterial and two fungal strains using the agar
      well diffusion and broth dilution methods. Petroleum ether, hexane, chloroform,
      acetone and ethanol extracts exhibited antibacterial as well as antifungal
      activity. Acetone and hexane extracts of both tubers showed comparable
      antimicrobial activity as indicated by minimum inhibitory concentration (MIC)
      values, but other extracts of Curcuma malabarica showed significantly lower
      activity than those of Curcuma zedoaria. The MIC values for different strains and
      extracts ranged from 0.01 to 0.15 mg/ml in Curcuma zedoaria and from 0.01 to 0.94
      mg/ml in Curcuma malabarica. Staphylococcus aureus (Gram positive) was inhibited
      by Curcuma malabarica but not by Curcuma zedoaria. This study is the first report
      of the antimicrobial properties of Curcuma malabarica. The findings also support
      the use of Curcuma zedoaria tubers in traditional medicine for the treatment of
      bacterial and fungal infections.

PMID- 15848036
TI  - Analgesic and anti-inflammatory properties of Nelsonia canescens leaf extract.
AB  - An ethanolic extract of the dried leaves of Nelsonia canescens was investigated
      for anti-inflammatory and analgesic activities in rat. In the test for anti
      inflammatory activity, the extract at the doses of 50-200 mg/kg significantly
      (P<0.05) inhibited carrageenan-induced paw oedema and cotton pellet granuloma.
      Likewise, at the same doses the extract exhibited analgesic activity in both the
      hot plate latency assay (hot plate maintained at 55 degrees C) and on the early
      and late phases of formalin-induced paw licking in rats. The result of the
      present study confirm that Nelsonia canescens has analgesic and anti-inflammatory
      activities. These findings also justify the traditional use of the plant for
      treating pain.

PMID- 15848037
TI  - Effects of bee venom on the pro-inflammatory responses in RAW264.7 macrophage
      cell line.
AB  - The purpose of this study is to elucidate the molecular mechanism of anti
      inflammatory effect of bee venom (BV), which has been used for the treatment of
      various inflammatory diseases in oriental medicine. With this aim, we examined
      the effects of BV on the nitric oxide (NO) production by lipopolysaccharide (LPS)
      or sodium nitroprusside in RAW264.7 macrophages. We further investigated the
      effects of BV on the expression of inducible nitric oxide synthase (iNOS),
      cyclooxygenase-2 (COX-2), nuclear factor-kappaB (NF-kappaB) and mitogen-activated
      protein kinase (MAPK) with RT-PCR in LPS-stimulated RAW264.7 cells. BV suppressed
      the NO production and decreased the levels of iNOS, COX-2, NF-kappaB and MAPK
      mRNA in a dose-dependent manner. These results suggest that BV has an anti
      inflammatory effect by inhibiting iNOS and COX-2 expression, possibly through
      suppression of NF-kappaB and MAPK expression.

PMID- 15848038
TI  - Structural features of thermozymes.
AB  - Enzymes synthesized by thermophiles and hyperthermophiles are known as
      thermozymes. These enzymes are typically thermostable, or resistant to
      irreversible inactivation at high temperatures, and thermophilic, i.e. optimally
      active at elevated temperatures between 60 and 125 degrees C. Enzyme
      thermostability encompasses thermodynamic stability and kinetic stability.
      Thermodynamic stability is defined by the enzyme's free energy of stabilization
      (deltaG(stab)) and by its melting temperature (Tm). An enzyme's kinetic stability
      is often expressed as its halflife (t1/2) at defined temperature. DeltaG(stab) of
      thermophilic proteins is 5-20 kcal/mol higher than that of mesophilic proteins.
      The thermostability mechanisms for thermozymes are varied and depend on the
      enzyme; nevertheless, some common features can be identified as contributing to
      stability. These features include more interactions (i.e. hydrogen bonds,
      electrostatic interactions, hydrophobic interactions, disulfide bonds, metal
      binding) than in less stable enzymes and superior conformational structure (i.e.
      more rigid, higher packing efficiency, reduced entropy of unfolding,
      conformational strain release and stability of alpha-helix). Understanding of the
      stabilizing features will greatly facilitate reengineering of some of the
      mesozymes to more stable thermozymes.

PMID- 15848039
TI  - Elicitor signal transduction leading to production of plant secondary
      metabolites.
AB  - Plant secondary metabolites are unique sources for pharmaceuticals, food
      additives, flavors, and other industrial materials. Accumulation of such
      metabolites often occurs in plants subjected to stresses including various
      elicitors or signal molecules. Understanding signal transduction paths underlying
      elicitor-induced production of secondary metabolites is important for optimizing
      their commercial production. This paper summarizes progress made on several
      aspects of elicitor signal transduction leading to production of plant secondary
      metabolites, including: elicitor signal perception by various receptors of
      plants; avirulence determinants and corresponding plant R proteins;
      heterotrimeric and small GTP binding proteins; ion fluxes, especially Ca2+
      influx, and Ca2+ signaling; medium alkalinization and cytoplasmic acidification;
      oxidative burst and reactive oxygen species; inositol trisphosphates and cyclic
      nucleotides (cAMP and cGMP); salicylic acid and nitric oxide; jasmonate,
      ethylene, and abscisic acid signaling; oxylipin signals such as allene oxide
      synthase-dependent jasmonate and hydroperoxide lyase-dependent C12 and C6
      volatiles; as well as other lipid messengers such as lysophosphatidylcholine,
      phosphatidic acid, and diacylglycerol. All these signal components are employed
      directly or indirectly by elicitors for induction of plant secondary metabolite
      accumulation. Cross-talk between different signaling pathways is very common in
      plant defense response, thus the cross-talk amongst these signaling pathways,
      such as elicitor and jasmonate, jasmonate and ethylene, and each of these with
      reactive oxygen species, is discussed separately. This review also highlights the
      integration of multiple signaling pathways into or by transcription factors, as
      well as the linkage of the above signal components in elicitor signaling network
      through protein phosphorylation and dephosphorylation. Some perspectives on
      elicitor signal transduction and plant secondary metabolism at the transcriptome
      and metabolome levels are also presented.

PMID- 15848040
TI  - Therapeutic effect of CpG-enriched plasmid administration on the tight-skin mouse
      model of scleroderma.
AB  - Immunostimulatory CpG motifs can preferentially induce Th1 immune responses and
      have been applied to treat Th2-dominant disease. In this study, we investigated
      whether a plasmid with the addition of 20 copies of an immunostimulatory CpG
      motif (pB-CpG20) might prevent the development of scleroderma-like syndrome in
      tight-skin (Tsk/+) mice. Administration of pB-CpG20 to Tsk/+mice every 3 weeks
      starting at the age of 1 week reduced skin thickness and collagen content
      compared to that of pB or saline. The reduction was long lasting even after
      halting the treatment. Furthermore, this treatment partially reduced the
      production of anti-nuclear antibodies although it did not decrease the incidence
      of lung emphysema. pB-CpG20 increased the number of spleen cells secreting IFN
      gamma and reduced that of the cells secreting IL-4 in vivo and in vitro compared
      to saline. These results suggest that repeated administration of a CpG-enriched
      plasmid can ameliorate scleroderma-like syndrome by biasing Th1 immunity in young
      Tsk/+mice.

PMID- 15848041
TI  - Anti-ergotypic T cells in naive rats.
AB  - T regulatory cells play an important role in regulating T cell responses. Anti
      ergotypic T cells are a subset of regulatory T cells that proliferate in response
      to activation markers, ergotopes, expressed on activated, and not on resting
      syngeneic T cells. Here we report the presence of anti-ergotypic T cells in lymph
      nodes, spleens and thymuses of naive rats. The development of anti-ergotypic T
      cells appeared to be independent of antigen priming, as thymocytes from one-day
      old rats exhibited significant anti-ergotypic proliferative responses. The anti
      ergotypic T cells were found to be of the CD8+ phenotype, and included both
      TCRalpha/beta+ and TCRgamma/delta+ T cells. The TCRgamma/delta+ anti-ergotypic T
      cells secreted IFNgamma and TNFalpha in response to activated T cells; the
      TCRalpha/beta+ T cells proliferated but did not secret detectable cytokines. We
      found that the interaction between the anti-ergotypic T cells and stimulator T
      cells required cell-to-cell contact between the T cells. Professional APCs were
      not needed. The response of the TCRalpha/beta+CD8+ anti-ergotypic T cells was MHC
      I restricted and B7-CD28 dependent; the response of the TCRgamma/delta+ anti
      ergotypic T cells was B7-CD28 dependent, but was not inhibited by antibodies to
      classical MHC-I or MHC-II molecules. The existence of anti-ergotypic T cells in
      naive animals suggests that these cells might have a role in the regulation and
      maintenance of the immune system.

PMID- 15848042
TI  - Induction of humoral responses specific for paraneoplastic cerebellar
      degeneration-associated antigen by whole recombinant yeast immunization.
AB  - Paraneoplastic cerebellar degeneration (PCD) is a potent autoimmune disorder in
      which antigen-driven responses toward the onconeural antigen are assumed to occur
      in patients. Yeast cell wall has adjuvant capacity and provides immunostimulatory
      effects of the antigen expressing in viable cells. The recombinant yeast
      expressing the PCD-associated antigen may become an immunogen for inducing PCD
      associated autoimmunity in mice. We attempted to induce autoimmune responses with
      whole recombinant yeast expressing PCD-associated antigen. SJL/J strain of mouse
      is found to be a responder to the major epitope on the antigen for anti-Purkinje
      cell antibodies, and whole recombinant yeast could induce cellular and humoral
      autoimmune responses in vivo ion SJL/J mice. The immunization technique based on
      the recombinant yeast expressing a PCD-associated antigen provides a new tool for
      analyzing the underlying immunological pathomechanisms of PCD.

PMID- 15848043
TI  - Phylogenetic and immunological definition of four lipoylated proteins from
      Novosphingobium aromaticivorans, implications for primary biliary cirrhosis.
AB  - Novosphingobium aromaticivorans, a unique ubiquitous bacterium that metabolizes
      xenobiotics and activates environmental estrogens, has been suggested as a
      pathogenic factor in the development of primary biliary cirrhosis (PBC). To
      define the molecular basis of PBC sera reactivity, we investigated the
      characteristic of the bacterial antigens involved. We cloned and sequenced four
      genes from N. aromaticivorans coding for immunoreactive proteins, arbitrarily
      named Novo 1 through Novo 4. We subsequently analyzed these proteins for their
      homology to known mitochondrial proteins and defined their reactivity using
      monoclonal antibodies (mAbs), rabbit anti-lipoic acid antibody, and PBC/control
      sera. Moreover, we studied their phylogenetic relation with the known PBC
      autoantigens. Novo proteins have an extraordinary degree of amino acid homology
      with all of the major human mitochondrial autoantigens PDC-E2 (Novo 1 and 2),
      OGDC-E2 (Novo 3), and BCOADC-E2 (Novo 4). Moreover, Novo 1-4 contain a lipoylated
      domain, are recognized by AMA-positive sera, and react with specific mAbs to
      mitochondrial antigens. Interestingly, the phylogenetic relation of the proteins
      emphasizes the conservation of the lipoylated domain. In conclusion, our data
      provide a high degree of confidence that N. aromaticivorans may potentiate the
      breakdown of self tolerance in genetically susceptible individuals.

PMID- 15848044
TI  - Anticardiolipin antibodies in children with atopic dermatitis.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease with a
      multifactorial etiology. Immunological abnormalities (cell-mediated immune
      hyperactivity, elevated IgE serum levels and eosinophil-derived mediators) have
      been observed. In a recent issue, Szakos et al. describe, in children with
      extrinsic type of AD, an association between the occurrence of anticardiolipin
      (ACL) IgM and specific IgE against mite, and also in relation to the severity of
      the disease. We studied 51 children (35 males and 16 females, mean age 44 months)
      with AD, whose diagnosis was made on the basis of Hanifin and Rajka's criteria.
      The evaluation of the severity of the disease was made using the SCORAD index.
      Eleven children had intrinsic type AD (group A); 40 children had extrinsic type
      AD, 14 of them had specific IgE only against food allergens (group B); 26
      children had specific IgE also against inhalant allergens (group C). Twelve
      children without allergy were designated as the control group. Specific IgEs were
      determined using the CAP-System (Pharmacia, Uppsala, Sweden) for food and
      inhalant allergens. The measurement of ACL IgG and IgM was carried out by ELISA
      (Orgentec Diagnostika, Mainz, Germany). An increase in serum levels of ACL was
      observed in 13 children (25.5%): 1 child (9%) from group A, 7 children (50%) from
      group B and 5 children (19.2%) from group C with a statistically significant
      difference (P=0.038). Our study shows the presence of ACL-IgG above all in
      extrinsic AD, but no association was found between high levels of ACL and
      increased severity scoring of AD. Increased levels of ACL were observed in
      younger children (mean age 26.5 months; P=0.025) especially if sensitized against
      food allergens.

PMID- 15848045
TI  - Immunogenetic association in patients with antineutrophil cytoplasmic antibodies
      (ANCA) from Mumbai, Maharashtra, India.
AB  - Considerable genetic evidence exit for ANCA-associated vasculitis and
      pathogenesis. HLA A and B alleles identified serologically from 84 ANCA-positive
      patients were compared with 101 controls. Further subtyping were done in the 27
      "pauci-immune" vasculitis patients using the polymerase chain reaction based PCR
      SSOP technique and compared with controls (67). The results revealed that HLA A1
      (OR=4.00; p value 2.72E-05), B17 (OR=3.38; p value 0.0008) and HLA B40 (OR=2.74;
      p value 0.001) were significantly increased among ANCA-positive patients when
      compared with the controls. Further, the molecular subtypes A*0101 (OR=5.04; p
      value 0.0005), B*5801 (OR=4.47; p value 0.0002) and haplotype A*0101-B*5801
      (OR=4.47; p value 0.0001) were significantly increased among the autoimmune
      patients. The study revealed that HLA A1, B17 and B40 alleles are associated in
      production of antineutrophil autoantibodies and A*0101-B*5801 haplotype is
      significantly associated with autoimmune diseases and they may be invariably
      involved in disease pathogenesis in India.

PMID- 15848046
TI  - CD4 CD25high regulatory T cells are not impaired in patients with primary
      Sjogren's syndrome.
AB  - In animal models of autoimmunity, CD4 CD25high T cells play a key role in the
      control of the autoimmune process. Few studies have investigated the role of
      these cells in human autoimmune diseases. We aimed to investigate CD4 CD25high T
      cells in the peripheral blood of patients with primary Sjogren's syndrome (pSS).
      The proportion of blood CD4 CD25high T cells was determined by flow cytometry in
      21 patients with pSS as determined by the American-European consensus group
      criteria and two groups of controls (18 patients with lumbar back pain of
      mechanical origin and 15 healthy blood donors). The suppressive function of CD4
      CD25 cells was assessed using co-culture assays. The Vbeta repertoire of CD4 CD25
      T cells was examined by flow cytometry. The proportion of CD4 CD25 T cells
      depended on age in patients and controls. In an age-matched comparison, no
      significant difference was observed in the proportion of total CD4 CD25low T
      cells between patients with pSS and controls (P=0.36). In contrast, the pool of
      CD4 CD25high was significantly increased in patients with pSS (8.5% vs 4.1% in
      controls, P=0.04). There was a slight but not significant higher proportion of
      CD4 CD25high cells in patients with a more active disease. CD4 CD25 T cells in
      patients with pSS effectively suppressed the proliferation of CD4 CD25-
      autologous responder T cells. The Vbeta repertoire of regulatory T cells from
      patients with pSS was polyclonal and was not significantly restricted as compared
      with that in controls. Functional CD4 CD25high regulatory cells are increased in
      patients with established pSS, through a reactive feedback, despite ongoing
      autoimmunity. These results suggest that pSS does not occur as a result of
      reduced level of CD4 CD25high regulatory T cells, nor as a defect of inhibition
      of proliferation of responder cells.

PMID- 15848047
TI  - Evaluation of IDDM8 susceptibility locus in a Russian simplex family data set.
AB  - Type 1 diabetes (T1D) susceptibility locus, IDDM8, has been accurately mapped to
      200 kilobases at the terminal end of chromosome 6q27. This is within the region
      which harbours a cluster of three genes encoding proteasome subunit beta 1
      (PMSB1), TATA-box binding protein (TBP) and a homologue of mouse programming cell
      death activator 2 (PDCD2). In this study, we evaluated whether these genes
      contribute to T1D susceptibility using the transmission disequilibrium test of
      the data set from 114 affected Russian simplex families. The A allele of the
      G/A1180 single nucleotide polymorphism (SNP) at the PDCD2 gene, which was
      significant in its preferential transfer from parents to diabetic children (75
      transmissions vs. 47 non-transmissions, chi2=12.85, P corrected=0.0038), was
      found to be associated with T1D. G/A1180 dimorphism and two other SNPs, C/T771
      TBP and G/T(-271) PDCD2, were shown to share three common haplotypes, two of
      which (A-T-G and A-T-T) have been associated with higher development risk of T1D.
      The third haplotype (G-T-G) was related to having a lower risk of disease. These
      findings suggest that the PDCD2 gene is a likely susceptibility gene for T1D
      within IDDM8. However, it was not possible to exclude the TBP gene from being
      another putative susceptibility gene in this region.

PMID- 15848048
TI  - Prevalence and clinical significance of anticardiolipin antibodies in patients
      with type 1 autoimmune hepatitis.
AB  - There are few case reports on the association between autoimmune hepatitis (AIH)
      and anticardiolipin antibodies (anti-CLAbs) and/or antiphospholipid syndrome
      (APLS). We studied the anti-CLAbs prevalence in AIH and other hepatic diseases.
      We also investigated whether anti-CLAbs are co-factor dependent and which is
      their avidity since co-factor dependency or increased resistance is associated
      with APLS. Fifty-nine AIH patients, 228 HCV, 50 HBV, 123 with other non-viral and
      non-autoimmune liver disorders (nV-nALD) and 267 healthy people were investigated
      for anti-CLAbs and antibodies against beta-2-glycoprotein I (anti-beta2-GPI).
      Resistance of IgG anti-CLAbs was evaluated using 2 M urea. IgG anti-CLAbs
      detected in 39% of AIH, 19.7% of HCV (p=0.006), 14% of HBV (p=0.01), 8.1% of nV
      nALD (p=0.000) and 1.1% of healthy (p=0.000). IgG anti-CLAbs were associated with
      the presence of cirrhosis and active AIH while their resistance to urea was high.
      Anti-beta2-GPI was detected in two AIH patients. We demonstrated a significantly
      higher prevalence of anti-CLAbs in patients with AIH compared to other diseases
      and healthy people. Anti-CLAbs were associated with AIH stage but no association
      was found with APLS clinical manifestations (thrombosis, pregnancy morbidity,
      thrombocytopenia). However, their avidity was comparable with that of APLS
      indicating the need for prospective studies in order to address whether anti
      CLAbs in AIH may contribute to the progression of liver disease or APLS
      development.

PMID- 15848049
TI  - Myasthenia gravis patients with low plasma IL-6 and IFN-gamma benefit from
      etanercept treatment.
AB  - Steroid-dependent myasthenia gravis patients improved following treatment with
      etanercept (recombinant human TNF receptor:Fc) in a prospective pilot trial.
      While the plasma anti-acetylcholine receptor antibody levels remained unaffected,
      etanercept treatment increased plasma levels of C3, circulating immune complexes,
      IL-10 and IFN-gamma. There was a direct correlation between plasma IL-6, TNF
      alpha and IFN-gamma levels and the post-treatment clinical scores of patients.
      Moreover, patients with lower pre-treatment plasma IL-6 and IFN-gamma levels
      attained better clinical improvement following etanercept treatment.

PMID- 15848050
TI  - Mucoadhesives in the gastrointestinal tract: revisiting the literature for novel
      applications.
AB  - This article investigates applying mucoadhesives to manipulate friction and to
      achieve locomotion of an alternative colonoscopic device through the large
      intestine. Considering that such an application of mucoadhesives is new, the
      authors recognised the need to revisit the different aspects of mucoadhesion in
      the gastrointestinal tract on the basis of the literature and to re-evaluate them
      according to the requirements for intestinal locomotion. First, the material
      properties, which are critical for the locomotion mechanism and specific
      categories of mucoadhesives characterised by those critical properties were
      identified. The next step was to examine the structural characteristics of those
      categories to specify which of the already synthesised mucoadhesives are
      promising candidates for friction manipulation. Then, the response of those
      mucoadhesives to a number of environmental stimuli was examined. At the end, two
      in vitro experiments were carried out to study the potential of mucoadhesives for
      intestinal locomotion. A comparative analysis of the role of mucoadhesives in
      drug delivery and in intestinal locomotion leads to the conclusion that the two
      applications can be approached to one extent with common principles, but crucial
      differences are present as well.

PMID- 15848051
TI  - Pharmacokinetics of an immediate release, a controlled release and a two pulse
      dosage form in dogs.
AB  - Clinical studies have shown that circadian patterns influence the
      pharmacokinetics of certain drugs used in the treatment of different diseases.
      For such drugs, the bioavailability is influenced by the time of administration.
      The objective of this study was to investigate differences in the pharmacokinetic
      patterns between a pulsatile drug delivery system using a pulsatile capsule, an
      immediate release tablet and a controlled release tablet. Metoprolol was chosen
      as a model drug because of its high solubility and high permeability pattern
      throughout the GI tract. The dosage forms were administered to four dogs and the
      plasma levels were measured using LC-MS/MS. Pharmacokinetic parameters were
      determined for each dosage form. Fluctuations in the plasma time curves over the
      observation period indicated that physiological factors like motility have an
      influence on the drug absorption. The comparison of the plasma time curves of the
      dosage forms showed that each dosage form caused significant differences in the
      drug plasma levels. The pulsatile drug delivery capsule caused two defined C(max)
      values for each dose between 1-1.75 and 2.5-3.5h. Implications for the use of a
      pulsatile drug delivery device for chronopharmacotherapy are discussed. Pulsatile
      drug delivery offers a promising way for chronopharmacotherapy if the time of
      administration and pulse time are adjusted to the circadian pattern.

PMID- 15848052
TI  - Topical delivery of cyclosporin A: an in vitro study using monoolein as a
      penetration enhancer.
AB  - Topical delivery of cyclosporin A (CysA) is of great interest for the treatment
      of autoimmune skin disorders, but it is frequently ineffective due to poor drug
      penetration in the skin. The present study was aimed at investigating whether the
      presence of monoolein (a lipidic penetration enhancer) in a preparation of
      propylene glycol can improve CysA delivery to the skin. CysA was incorporated in
      a propylene glycol preparation containing 5-70% (w/w) of monoolein. The topical
      (to the skin) and transdermal (across the skin) delivery of CysA were evaluated
      in vitro using porcine ear skin mounted in a Franz diffusion cell. CysA was
      quantified by UV-HPLC. At 5%, monoolein increased only the transdermal delivery
      of CysA. At 10%, it increased both topical and transdermal delivery. When the
      concentration of monoolein was further increased (20-70% w/w), an interesting
      phenomenon was observed: the topical delivery of CysA was still elevated but its
      transdermal delivery was substantially reduced. It was concluded that monoolein
      (in propylene glycol formulations) can promote the topical delivery of CysA, with
      reduced transdermal delivery.

PMID- 15848053
TI  - In vitro availability of kaempferol glycosides from cream formulations of
      methanolic extract of the leaves of Melilotus elegans.
AB  - In Ethiopian traditional medicine, Melilotus elegans Salzm. ex Ser. (Leguminosae)
      is used for the treatment of haemorrhoids and lacerated wounds. In view of its
      wide spread use and proven anti-inflammatory activity, 80% methanolic extract of
      the leaves was formulated into creams. HPLC/UV and MS studies revealed the
      presence of flavonoids, of which kaempferol was the major aglycone. Quantitative
      estimation of kaempferol in the hydrolyzed extract as determined by HPLC/UV was
      found to be 16.3+/-0.93 microg/mg (n=6, range) of extract. The in vitro release
      profiles of kaempferol glycosides (quantified as kaempferol equivalent) from the
      cream formulations in a multilayer membrane system indicated that a lipophilic
      cream of the extract provides higher release of kaempferol glycosides than
      hydrophilic and amphiphilic ones. Over a study period of 4h, the lipophilic cream
      released 66+/-5.70% of kaempferol glycosides, while the hydrophilic and
      amphiphilic creams resulted in 55+/-2.77 and 38+/-2.30% release, respectively.

PMID- 15848054
TI  - Cyclodextrin complexes of valdecoxib: properties and anti-inflammatory activity
      in rat.
AB  - The influence of natural beta-cyclodextrin and its hydrophilic derivatives
      (HPbetaCd and SBE7betaCd) on the in vitro dissolution rate, in vivo absorption
      and oral bioavailability of a poorly water soluble anti-inflammatory agent,
      valdecoxib (VALD) was studied. Equimolar drug-cyclodextrin solid complexes were
      prepared by kneading and coevaporation methods and characterized by infrared
      spectroscopy, differential scanning calorimetry, X-ray diffraction. In the liquid
      state, the cyclodextrin complexes were studied using phase solubility analysis,
      (1)H nuclear magnetic resonance and circular dichroism spectroscopy. Drug
      solubility and dissolution rate in distilled water were notably improved by
      employing the betaCds. The DP(15) (i.e. percent of dissolved VALD at 15 min) was
      10.5% for the pure drug and 50, 91 and 93% for VALD-betaCd, VALD-HPbetaCd and
      VALD-SBE7betaCd complexes, respectively. Moreover, it was found that in the, the
      cyclodextrin complexes of drug showed significant improvement in the anti
      inflammatory activity.

PMID- 15848055
TI  - The effect of liposomes with superoxide dismutase on A2182 cells.
AB  - Differently charged liposomes were examined for the efficiency of delivery of
      Cu/Zn superoxide dismutase (CuZnSOD) to human lung epithelial cells, A2182, and
      their prospects of cell protection from oxidative agents. A2182 cells were
      treated with cationic, neutral and anionic liposomes with encapsulated CuZnSOD.
      Untreated cells and cells pre-treated with liposome-encapsulated CuZnSOD were
      exposed to oxidative stress caused by xanthine/xanthine oxidase. Cellular
      antioxidant response was monitored for 4 or 24h after the beginning of oxidative
      stress induced by the activity of superoxide dismutase (SOD) and total
      glutathione concentration. CuZnSOD-loaded liposomes increased the SOD activity of
      A2182 cells 24h after treatment. The highest increase of cellular SOD, by 108%,
      was achieved using anionic liposomes. Neutral and cationic liposomes increased
      cellular SOD by 83 and 85%, respectively. Cationic liposomes were the most
      cytotoxic. Exposure of untreated cells to oxidative stress increased the cellular
      glutathione level after 24h. Cells pre-treated with liposome-encapsulated CuZnSOD
      were protected from oxidative stress, as shown by the unchanged concentration of
      cellular glutathione.

PMID- 15848056
TI  - Carboxymethyl high amylose starch (CM-HAS) as excipient for Escherichia coli oral
      formulations.
AB  - Carboxymethyl high amylose starch (CM-HAS) is proposed as a novel excipient for
      oral tablet formulation of bioactive agents ensuring their protection in the
      stomach and delivery in the intestine. Three variants of CM-HAS, with different
      degrees of substitution, were synthesized by starch treatment with various
      amounts of monochloroacetic acid. The products were dried in powder form and
      tablets were obtained by direct compression of mixed powders of polymeric
      excipient and lyophilized Escherichia coli (E. coli) bacteria. Dosage forms of CM
      HAS are unswollen and compact in acidic medium, ensuring protection of active
      agents against acidity. Release of bacteria from CM-HAS tablets is based on the
      fast swelling of the tablets during the passage from gastric acidity to alkaline
      intestinal medium, enzymatic hydrolysis triggering their rapid, almost total
      dissolution. The bacteria thus formulated displayed higher survival rates in
      acidic gastric conditions and for longer periods than the free bacteria or than
      the bacteria formulated with the non-derivatized starch. The CM-HAS selected
      matrix also assured a good viability of bacteria after 6 months under
      refrigeration.

PMID- 15848057
TI  - Polymethacrylates as crystallization inhibitors in monolayer transdermal patches
      containing ibuprofen.
AB  - The feasibility of a monolayer patch based on polydimethylsiloxane pressure
      sensitive adhesive containing ibuprofen (IB) in supersaturated condition was
      studied. The efficacy of three low molecular weight excipients (propylene glycol,
      PG, Cremophor EL and Cremophor RH) and of two copolymers of methacrylic acid
      (Eudragit((R)) E, EuE, and Eudragit((R)) RL, EuRL) as IB crystallization
      inhibitors was tested. The performances of the patches were evaluated in terms of
      drug release and human stratum corneum and epidermis (SCE) permeation profile.
      The interactions between IB and the other excipients were investigated by ATR-FT
      IR spectroscopy. The stability of the patches, prepared without adding
      crystallization inhibitors, was unsatisfactory because crystals grew in less than
      1 month. Among the low molecular weight molecules, only PG inhibited the IB
      crystallization up to 50 days without affecting the IB skin permeation profile.
      The addition of EuE or EuRL in the matrices prevented drug crystallization for
      more than 12 months. EuE significantly reduced the IB in vitro release rate and
      the IB permeated amount through the SCE compared to other formulations. These
      phenomena are attributed to a stronger association between IB and EuE than IB and
      EuRL.

PMID- 15848058
TI  - Development of tretinoin gels for enhanced transdermal delivery.
AB  - To develop the new gel formulations that show sustained release for a period of
      time, the bioadhesive carbopol gels containing tretinoin were prepared. The
      release characteristics of drug from the carbopol gel were studied according to
      temperature, receptor medium and drug concentration. For the enhancement of its
      percutaneous absorption, some kinds of penetration enhancer were used. As the
      concentration of drug increased, the release of drug from the gel increased,
      showing concentration dependency. The increase of temperature showed the
      increased drug release, depending on the activation energy of permeation. Among
      the enhancers used such as the glycols and the non-ionic surfactants,
      polyoxyethylene 2-oleyl ether showed the best enhancing effect. The carbopol gels
      of tretinoin containing an enhancer could be developed for the enhanced
      transdermal delivery of drug.

PMID- 15848059
TI  - Effect of SBE7-beta-cyclodextrin complexation on carbamazepine release from
      sustained release beads.
AB  - The effect of SBE7-beta-cyclodextrin together with hydroxypropylmethyl cellulose
      (HPMC) or polyvinylpyrrolidone (PVP) on the saturated solubility and delivery of
      carbamazepine (a poorly soluble drug) from sustained release (SR) beads was
      investigated. Carbamazepine solubility at room temperature increased from 0.1 to
      5.4mg/ml by forming an inclusion complex with SBE7-beta-cyclodextrin (15%w/v).
      HPMC (0.1%w/v) also increased the aqueous solubility of carbamazepine, acting
      both alone and synergistically with SBE7-beta-cyclodextrin, to produce solubility
      values of 0.26 and 8.1mg/ml respectively. PVP (0.1-0.5%w/v) had no effect on
      carbamazepine solubility, either alone or in combination with SBE7-beta
      cyclodextrin. The addition of SBE7-beta-cyclodextrin to SR beads increased the
      rate of carbamazepine release. In addition, comparable release rates where
      obtained when lower ratios of SBE7-beta-cyclodextrin together HPMC were
      incorporated in the SR bead. Therefore this ternary drug cyclodextrin polymer
      system was considered preferable over the binary drug cyclodextrin system for SR
      beads, as less cyclodextrin was required. However, both binary and ternary
      approaches were considered suitable techniques to improve the release rate and
      potentially the in vivo bioavailability of poorly soluble drugs that had
      previously exhibited slow or incomplete release from SR beads.

PMID- 15848060
TI  - Comparison of powder produced by evaporative precipitation into aqueous solution
      (EPAS) and spray freezing into liquid (SFL) technologies using novel Z-contrast
      STEM and complimentary techniques.
AB  - The objective of this study was to compare the properties of particles formed by
      nucleation and polymer stabilization (e.g. evaporative precipitation into aqueous
      solution (EPAS)) versus rapid freezing (e.g. spray freezing into liquid (SFL)).
      Powders formed by EPAS and SFL, composed of danazol and PVP K-15 in a 1:1 ratio,
      were characterized using X-ray powder diffraction, modulated differential
      scanning calorimetry (MDSC), contact angle determination, dissolution, scanning
      electron microscopy (SEM), environmental scanning electron microscopy (ESEM), BET
      specific surface area, and Z-contrast scanning transmission electron microscopy
      (STEM). Large differences in particle morphologies and properties were observed
      and explained in terms of the particle formation mechanisms. Both techniques
      produced amorphous powders with high T(g) and low contact angle values. However,
      STEM analysis showed highly porous bicontinuous nanostructured 30nm particles
      connected by narrow bridges for SFL versus aggregated 500 nm primary particles
      for EPAS. The combination of STEM and other characterization techniques indicates
      solid solutions were formed for the SFL powders consistent with rapid freezing.
      In contrast, the EPAS particle cores are enriched in hydrophobic API and the
      outer surface is enriched in the hydrophilic polymer, with less miscibility than
      in the SFL powders. Consequently, dissolution rates are faster for the SFL
      particles, although both techniques enhanced dissolution rates of the API.

PMID- 15848061
TI  - Design of a phytosphingosine-containing, positively-charged nanoemulsion as a
      colloidal carrier system for dermal application of ceramides.
AB  - Positively charged oil/water (o/w) nanoemulsions (PN) are effective vehicles to
      change the permeability of the skin. This study focused on the preparation and
      characterisation of phytosphingosine (PS) containing PN (PPN) which serve as
      colloidal carriers for the dermal application of ceramide IIIB (CIIIB) and the
      stratum corneum (SC) lipids (PPNSC) such as ceramide III (CIII), cholesterol, and
      palmitic acid. The investigations were conducted using appropriate emulsification
      and homogenisation processing conditions to optimise PPNSC with regard to droplet
      size, physical stability, and solubility of PS, CIII and CIIIB. A decrease in
      droplet size was observed through eight homogenisation cycles at a pressure of
      500 bar and a temperature of 50 degrees C. Above these optimal values, an
      increase in droplet size was observed. PS and ceramides have low solubilities in
      oil and water. When Lipoid E-80 (LE80) was added to the oil phase, the solubility
      of PS and ceramides increased, indicating some interactions shown by DSC
      measurements. SC lipids and CIIIB could be successfully incorporated in PPN
      without producing any physical instability. The high stability of PPNSC is
      probably due to the presence of a hydrophilic (Tween 80) and a lipophilic
      surfactant (LE80), supported by the lipophilic cosurfactant PS, at the o/w
      interface. It was shown that PS was responsible for the positive charge and thus
      supported the high physical stability of PPNSC. This optimised emulsion was
      selected for further skin absorption evaluation.

PMID- 15848062
TI  - Diclofenac salts, II. Solid dispersions in PEG6000 and Gelucire 50/13.
AB  - A number of systems were prepared at five compositions (5, 10, 20, 30 and 40%
      w/w) of diclofenac/N-(2-hydroxyethyl) pyrrolidine salt and acidic diclofenac in
      PEG6000 and Gelucire 50/13, as physical mixtures and as solid dispersions. Powder
      X-ray diffractograms for the systems examined show shifted and normal peaks,
      suggesting that the drug is present inside the samples in different physical
      states. Differential scanning calorimetry does not offer important information,
      since drug solubility into the carriers increases with temperature and
      thermograms show only the melting point peak of the carriers. Hot-stage
      microscopy examination explains that, in high concentration samples, the drug is
      present either dissolved into the carriers, or precipitated as microcrystals, or
      undissolved crystals of larger size. Gelucire 50/13 allows the formation of
      larger crystals than PEG, using both the chemical forms of the drug. The release
      percentage of the drug from PEG6000/acidic diclofenac reaches 50% after few
      minutes in the most favourable case and appears to be dependent on the
      composition of the samples: the more diclofenac is present as dissolved in the
      pre-treated samples, the higher is the release. The optimum composition was found
      in the range of 5-10% w/w.

PMID- 15848063
TI  - Novel nanoparticulate carrier system based on carnauba wax and decyl oleate for
      the dispersion of inorganic sunscreens in aqueous media.
AB  - The purpose of this study was to characterize carrier systems for inorganic
      sunscreens based on a matrix composed of carnauba wax and decyl oleate.
      Ultraviolet radiation attenuators like barium sulfate, strontium carbonate and
      titanium dioxide were tested. The lipid matrices were used either as capsules or
      as accompanying vehicles for the pigments in aqueous dispersions. Manufacturing
      was performed using high pressure homogenization at 300bar and a temperature of
      75 degrees C. To evaluate the effect of the pigments on the crystalline structure
      of the wax-oil mixture, X-ray diffraction and differential scanning calorimetry
      were used. Further parameters determined were particle size, polydispersity
      index, z-potential, viscosity and sun protection factor (SPF). Transmission
      electron microscopy was also applied for visualization of nanoparticles. The X
      ray diffraction patterns and the melting points of the lipid mixtures remained
      unchanged after the pigments were added. The particle sizes of the encapsulated
      species ranged from 239 to 749.9nm showing polydispersity values between 0.100
      and 0.425. Surface charge measurements comprising values up to -40.8mV denoted
      the presence of stable dispersions. The formulations could be described as ideal
      viscous presenting viscosities in a range of 1.40-20.5mPas. Significant increases
      in SPF up to about 50 were reported after the encapsulation of titanium dioxide.
      Freeze fracture micrographs confirmed the presence of encapsulated inorganic
      crystals.

PMID- 15848064
TI  - Synthesis and characterisation of novel nanospheres made from amphiphilic
      perfluoroalkylthio-beta-cyclodextrins.
AB  - This work describes the synthesis of new amphiphilic perfluorohexyl- and
      perfluorooctyl-propanethio-beta-cyclodextrins and the comparison of the ability
      of these molecules and alkyl analogue, nonanethio-beta-cyclodextrin to form
      nanospheres. Nanospheres were prepared using nanoprecipitation method
      (perfluoroalkylthio-beta-cyclodextrin in THF [0.11 x 10(-3)M], stirring rate
      700rpm, addition of aqueous phase at 64 degrees C into organic phase at 50
      degrees C). They were characterised by Photon Correlation Spectroscopy (PCS) and
      by electron microscopy (SEM and cryo-TEM). The nanospheres prepared from these
      new beta-cyclodextrin derivatives have an average size of 260nm, and appear to be
      spherical in cryo-TEM images. Whereas alkyl analogue forms polydisperse
      aggregates with sizes in the range 60-350nm.

PMID- 15848065
TI  - The difficulty in the assessment of the compression behaviour of powder mixtures:
      Double layer tablets versus arithmetic additivity rule.
AB  - The weighted arithmetic mean from values of a feature derived from the individual
      components is often used to calculate the theoretically expected compression
      behaviour of powder mixtures if no interparticulate interactions between the
      components occur. Alternatively, simulated and experimental double layer tablets
      are presented. The suitability of the various methods to serve as a reference for
      the assessment of the compression behaviour of powder mixtures shall be compared.
      Narrow and similar sieve fractions of maltitol and metamizol were mixed in
      various ratios of true volumes. Constant total true volumes of the single
      substances, powder mixtures, and layered powders of the same composition were
      compressed on an eccentric tabletting machine to a constant maximum geometric
      mean punch force. In addition, the compression of double layer tablets was
      mathematically simulated from the dynamic relative density-force data of the pure
      materials. At a given momentary force, the relative density of a simulated double
      layered powder bed is given by the harmonic mean of the relative density values
      of the pure materials weighted by their true volume fractions. The results show
      that the total, the net, and the expansion work change indeed almost linearly
      with the true volume fraction of the components in the double layer tablets, with
      the consequence that the plasticity index (=net work/total workx100) proceeds non
      linearly. The slope of the Heckel plot 'at pressure' and the apparent mean yield
      pressure obtained from these Heckel data are non-linearly related to the true
      volume fraction. If the weighted arithmetic mean is used to analyse the
      compression behaviour of the powder mixtures, results are obtained which are
      incompatible or even contradictory between interrelated features. On the other
      hand, the double layer model provides a consistent evaluation. A good agreement
      between the results of the experimental and the simulated double layer tablets is
      found.

PMID- 15848066
TI  - The influence of bile salts and mixed micelles on the pharmacokinetics of quinine
      in rabbits.
AB  - The bioavailability of orally administered drugs can be influenced by
      interactions with food components and by physico-chemical conditions in the upper
      gastrointestinal tract. Normally, bile salts enhance the transport of lipophilic
      drugs across mucosal membranes. Bile salts are able to form stable mixed micelles
      consisting of fatty acids and phospholipids. Conventional micellar systems are
      known to solubilize lipophilic drugs having a low bioavailability. The influence
      of bile salts and mixed micelles on the pharmacokinetics of the lipophilic drug
      quinine was investigated in rabbits. Female rabbits were given intraduadenally
      quinine (5 mg/kg body weight) without and with incorporation into the micellar or
      mixed micellar systems. Blood was collected every 30 min for 6 h. In plasma,
      concentration of quinine was measured using HPLC. The plasma concentration-time
      profiles of quinine were significantly lower within the first 2 h after
      administration in presence of both the sodium salt of glycodeoxycholic acid
      (above the critical micellar concentration) as well as of mixed micellar systems
      consisting of glycodeoxycholic acid and palmitic acid and/or lecithin. The
      pharmacokinetic parameters AUC (relative bioavailability) and c(max) of quinine
      were significantly decreased by micellar systems in rabbits. These mixed micellar
      systems lower and not as expected, increase the absorption of quinine in vivo.
      Therefore, quinine should be orally administered at least 1h before food intake,
      particularly before fat intake.

PMID- 15848067
TI  - Compressibility of floating pellets with verapamil hydrochloride coated with
      dispersion Kollicoat SR 30 D.
AB  - The purpose of this study was to work out a method of compression of floating
      pellets with verapamil hydrochloride (VH) in a dose of 40 mg. It was assumed that
      this form should reside in the stomach floating for several hours and gradually
      release the drug in a controlled way. Compression of pellets into tablets, being
      a modern technological process, is much more perfect than enclosing them in a
      hard gelatin capsule. Kollicoat SR 30 D was selected for coating. In experiments
      three plasticizers were examined-propylene glycol, triethyl citrate and dibuthyl
      sebecate (all at concentration of 10%). It was found that VH release from pellets
      coated by the films of the same thickness (70 microm), however, containing
      plasticizers is considerably different. Pellets were prepared by wet granulation
      of powder mixture, spheronization of the granulated mass and coating of the cores
      with a sustained release film. Two kinds of cellulose, microcrystalline and
      powdered, and sodium hydrocarbonate were the main components of pellet core.
      Proper pellet coating film thickness, ensuring obtaining desirable VH release
      profile and flotation effect, was defined. X compositions of tablets with pellets
      were examined in order to obtain formulation, from which VH release would mostly
      approximate pellets before compressing. The best formulation was evaluated taking
      into account the effect of compression force an tablet hardness and friability,
      and pellet agglomeration and flotation. Tablet cross-section photographs were
      taken confirming necessary coating film thickness preventing their deformation
      caused by compressing into tablets.

PMID- 15848068
TI  - Quantification of the leaching of triethyl citrate/polysorbate 80 mixtures from
      Eudragit RS films by differential scanning calorimetry.
AB  - The influence of triethyl citrate and polysorbate 80 (Tween 80) on the glass
      transition temperature (T(G)) of Eudragit RS membranes was investigated using
      differential scanning calorimetry (DSC). The T(G)-decreasing effect of TEC and
      Tween 80 displayed an almost identical performance in extent at a linear
      relationship between weight proportion and T(G) resulting in a specific T(G)
      decrease (T(G,spec.)) of -1.98(K/%TEC) and -1.86(K/%Tween), respectively. Thus,
      the proportion of each adjuvant could be summarized as the plasticizer complex
      weight proportion (PC) with T(G,spec.)=1.96(K/%PC). Vice versa this linear
      relationship could be used to determine the proportion of plasticizer complex
      within the polymer membrane after swelling and diffusion processes, i.e.
      plasticizer leaching. For membranes containing 20% (w/w) TEC and 8% (w/w) Tween
      80 as plasticizer complex a fast leaching resulted during the dissolution test
      reaching an equilibrium at 6.08% (+/-0.5) PC after 30 min in demineralised water.
      The DSC method proved to be a simple method to determine plasticizer leaching via
      T(G), however, without respect on the film forming properties of the two
      different excipients. Plasticizing with TEC or TEC/Tween 80 mixtures led to
      smooth and continuous films, while plasticizing with Tween 80 only resulted in
      mosaic like fissured films.

PMID- 15848069
TI  - Humanized antibodies and their applications.

PMID- 15848070
TI  - Immunogenicity of engineered antibodies.
AB  - Administration of a therapeutic antibody can lead to an anti-antibody response
      (AAR). Much effort has been applied to engineering antibodies with as little as
      possible non-human structure to minimize such responses. Here, we review reported
      AAR to murine, mouse-human chimeric, and humanized antibodies. Replacement of
      mouse immunoglobulin constant regions with human ones effects the largest
      immunogenicity reduction. Humanization of variable domains effects a further
      decrease.

PMID- 15848071
TI  - Tailor-made antibody therapeutics.
AB  - Therapeutic antibodies represent one of the fastest growing areas of the
      pharmaceutical industry. There are currently 18 monoclonal antibodies in the
      market that have been approved by the FDA and over 150 in clinical developments.
      Driven by innovation and technological developments, scientists have gone beyond
      the traditional antibody molecules. Antibodies have been engineered in a variety
      of ways to meet the challenges posed by different biological settings. Described
      in this review is an abridged account of the different ways antibodies have been
      tailored to make them efficient drug molecules.

PMID- 15848072
TI  - SDR grafting--a new approach to antibody humanization.
AB  - A major impediment to the clinical utility of the murine monoclonal antibodies is
      their potential to elicit human anti-murine antibody (HAMA) response in patients.
      To circumvent this problem, murine antibodies have been genetically manipulated
      to progressively replace their murine content with the amino acid residues
      present in their human counterparts. To that end, murine antibodies have been
      humanized by grafting their complementarity determining regions (CDRs) onto the
      variable light (V(L)) and variable heavy (V(H)) frameworks of human
      immunoglobulin molecules, while retaining those murine framework residues deemed
      essential for the integrity of the antigen-combining site. However, the
      xenogeneic CDRs of the humanized antibodies may evoke anti-idiotypic (anti-Id)
      response in patients. To minimize the anti-Id response, a procedure to humanize
      xenogeneic antibodies has been described that is based on grafting, onto the
      human frameworks, only the specificity determining residues (SDRs), the CDR
      residues that are most crucial in the antibody-ligand interaction. The SDRs are
      identified through the help of the database of the three-dimensional structures
      of the antigen-antibody complexes of known structures or by mutational analysis
      of the antibody-combining site. An alternative approach to humanization, which
      involves retention of more CDR residues, is based on grafting of the
      'abbreviated' CDRs, the stretches of CDR residues that include all the SDRs. A
      procedure to assess the reactivity of the humanized antibody to sera from
      patients who had been administered the murine antibody has also been described.

PMID- 15848073
TI  - Use of human germline genes in a CDR homology-based approach to antibody
      humanization.
AB  - We report a new method of humanizing antibodies by complementarity determining
      region (CDR) grafting. Our method differs from others in that we choose human
      framework sequences from the set of human germline genes based on the structural
      similarity of the human CDRs to those of the mouse antibody to be humanized. The
      structural similarity is evaluated by scoring residue-to-residue homology of the
      mouse CDRs to human candidates with the same Chothia canonical structures. The
      method is illustrated with the humanization of the anti-lysozyme antibody D1.3.

PMID- 15848074
TI  - Antibody humanization by framework shuffling.
AB  - We report here the humanization of a mouse monoclonal antibody (mAb B233) using a
      new technique which we call framework shuffling. mAb B233 was raised against the
      human receptor tyrosine kinase EphA2 which is selectively up-regulated in many
      cancer cell lines and as such constitutes an attractive target for cancer
      therapy. The six CDRs of B233 were fused in-frame to pools of corresponding
      individual human frameworks. These human frameworks encompassed all known heavy
      and light (kappa) chain human germline genes. The resulting Fab combinatorial
      libraries were then screened for binding to the antigen. A two-step selection
      process, in which the light and heavy chains of the parental mAb were
      successively humanized, resulted in the identification of several humanized
      variants that retained binding to EphA2. More precisely, after conversion to
      human IgG1, the dissociation constants of three select fully humanized variants
      ranged from 3 to 48 nM. This brings the best framework-shuffled, humanized binder
      within 5-fold of the avidity of parental mAb B233. Importantly, these humanized
      IgGs also possessed biochemical activities similar to those of parental mAb B233
      as judged by induction of EphA2 phosphorylation. Thus, without requiring any
      rational design or structural information, this new humanization approach allows
      to rapidly identify various human framework combinations able to support the
      structural feature(s) of the CDRs which are essential for binding and functional
      activity.

PMID- 15848075
TI  - From rodent reagents to human therapeutics using antibody guided selection.
AB  - Guided selection is a method of producing a human version of a rodent or any
      other non-human antibody. The process is a serial transition from rodent to human
      via rodent-human chimaerics, through to a panel of human antibodies with similar
      characteristics to those of the starting rodent antibody. The guided selection
      process can be undertaken using either phage display or ribosome display, and
      chimaeric antibodies can be made either in series or parallel, with or without
      the retention of the original rodent CDR3s. Guided selection has successfully
      been used for the generation of a number of human versions of rodent antibodies,
      including HUMIRA, an inhibitor of tumour necrosis factor-alpha which is approved
      for the treatment of moderate to severe rheumatoid arthritis in over 40
      countries.

PMID- 15848076
TI  - Design of humanized antibodies: from anti-Tac to Zenapax.
AB  - Since the introduction of hybridoma technology, monoclonal antibodies have become
      one of the most important tools in the biosciences, finding diverse applications
      including their use in the therapy of human disease. Initial attempts to use
      monoclonal antibodies as therapeutics were hampered, however, by the potent
      immunogenicity of mouse (and other rodent) antibodies in humans. Humanization
      technology has made it possible to remove the immunogenicity associated with the
      use of rodent antibodies, or at least to reduce it to an acceptable level for
      clinical use in humans, thus facilitating the application of monoclonal
      antibodies to the treatment of human disease. To date, nine humanized monoclonal
      antibodies have been approved for use as human therapeutics in the United States.
      In this paper, we describe procedures for antibody humanization with an emphasis
      on strategies for designing humanized antibodies with the aid of computer-guided
      modeling of antibody variable domains, using as an example the humanized anti
      CD25 monoclonal antibody, Zenapax.

PMID- 15848077
TI  - Development of humanized antibodies as cancer therapeutics.
AB  - Recent success in the development of monoclonal antibody-based anti-cancer drugs
      has largely benefitted from the advancements made in recombinant technologies and
      cell culture production. These reagents, derived from the antibodies of mouse
      origin, while maintaining the exquisite specificity and affinity to the tumor
      antigens, have low immunogenicity and toxicity in human. High-level expressing
      cell clones are generated and used to produce large quantities of the recombinant
      antibodies in bioreactors in order to meet the clinical demand for therapeutic
      applications. In this report, the systems and general methodologies developed by
      us to construct and produce humanized antibodies from the parent mouse antibodies
      are described. Once the humanized antibodies are available, they can be applied
      in three principal forms for cancer therapy: (1) naked antibodies, (2) drug- or
      toxin conjugates, and (3) radioconjugates. Using the humanized anti-CD22
      (epratuzumab) and anti-carcinoembryonic antigen (ant-CEA; labetuzumab) antibody
      prototypes, clinical applications of naked and radiolabeled humanized monoclonal
      antibodies are described.

PMID- 15848078
TI  - [IVF failure: is it really unexplained or undiagnosed?].

PMID- 15848079
TI  - [Sperm DNA integrity as diagnosis and prognosis element of male fertility].
AB  - Recent progress in reproductive biology has improved comprehension physiology of
      the spermatozoa and on the fertilization mechanisms. This new knowledge has
      carried out the elaboration of tests on male fertility based on sperm genomic
      integrity. This review presents some of these techniques and brings a reflexion
      element on the application and use of sperm DNA integrity in the investigation of
      male fertility. The single cell gel electrophoresis (COMET assay), Sperm
      Chromatin Structure Assay (SCSA), In Situ Nick Translation (NT: Nick Translation)
      and Terminal Uridine Nick-End Labelling (TUNEL assay) are actually the most
      currently used techniques for the measure of sperm DNA integrity in research
      clinic. From a certain point of view, TUNEL assay, SCSA, COMET assay and NT assay
      are complementary. The TUNEL and COMET can measure single and double strand
      breaks of DNA, the SCSA can detect the abnormalities in the chromatin compaction
      and the NT assay can detect the single strand breaks of DNA. The exact origin of
      sperm DNA fragmentation is not established yet. However, several mechanisms have
      been proposed: defect in the chromatin compaction during spermiogenesis; reactive
      oxygen species production by immature spermatozoa; apoptosis during
      spermatogenesis. It becomes important to consider the possible consequences of
      the oocyte fertilization by a spermatozoon having a high degree of DNA
      fragmentation. The use in routine of some of these tests must however pass by a
      standardization of the inter laboratory protocols and obviously, by the
      establishment of both in vivo and in vitro discriminating threshold values in
      order for these tests to present a good predictive value for pregnancy outcome.

PMID- 15848080
TI  - [Diagnosis of adnexal torsion and predictive factors of adnexal necrosis].
AB  - OBJECTIVE: To determine the most relevant findings for diagnosis of adnexal
      torsion and predictive factors of adnexal necrosis. PATIENTS AND METHODS:
      Clinical, biological, ultrasound, pathologic and surgical findings in surgically
      confirmed cases of adnexal torsion treated over a five-year period in a
      gynaecologic emergency department were retrospectively reviewed. RESULTS: A total
      of 52 cases of adnexal torsion were studied. Abdominal pain was present in 80.8%,
      vomiting in 13.5% and fever only in 9.6%. Leukocytosis was noted in 19 (36.5%).
      The most frequent ultrasound findings were ovarian enlargement in 22 patients
      (42.3%), ovarian cysts in 26 (50%), and hyperechogenic parenchyma with follicles
      along the periphery of the ovary in 13 (25%). Age over 40 years and a delay to
      surgery longer than 10 hours were significantly associated with diagnosis of
      adnexal necrosis. DISCUSSION AND CONCLUSION: Prompt diagnosis of adnexal torsion
      requires a combination of clinical, biological and radiological evidence. No
      predictive factors of necrosis are found. Risk of adnexal torsion is potentially
      increased by waiting period for surgery and patient's age.

PMID- 15848081
TI  - [Value of fetal scalp lactate sampling during labour: a comparative study with
      scalp pH].
AB  - OBJECTIVE: To evaluate the validity and the feasibility of fetal scalp lactate
      sampling during labour in the assessment of non reassuring fetal status. PATIENTS
      AND METHOD: A prospective observational study was conducted on 129 fetal scalp
      blood samplings. Scalp lactate measurements were compared to scalp pH (gold
      standard procedure), neonatal cord blood gas (pH and lactates) and Apgar score.
      Pathological values taken were for scalp lactates>5 mmol/l, scalp pH<7.20, cord
      arterial pH<7.10, cord arterial lactates>6,35 mmol/l, and Apgar score<7 at one
      and five minutes. All measurements were performed using the Rapid Lab 860 device
      from Bayer. RESULTS: Scalp lactate correlated significantly with scalp pH (R=
      0.54, P=0.001), with umbilical artery pH (R=-0.46, P=0,01), with umbilical artery
      lactate (P=0.49, P=0.01), but with neither Apgar score at one minute (R=-0.21,
      ns) nor at 5 minutes (R=-0.11, ns). Scalp lactate at a cut-off value of 5 mmol/l
      had the same predictive values than scalp pH at 7.20 to predict neonatal
      acidosis. Sampling failure with scalp lactate was inferior to 1 vs 18% for scalp
      pH. DISCUSSION AND CONCLUSION: The measurement of lactate in fetal blood scalp
      seems correlated to the fetal scalp pH. It may be an attractive alternative to pH
      analysis and a useful tool for monitoring fetal asphyxia, especially with the
      advent of handheld devices requiring small sample volumes.

PMID- 15848082
TI  - [Side effects of induced abortion: results from a population-based survey].
AB  - OBJECTIVES: This study compares the gynaecological symptoms of women who have
      undergone an induced abortion to those who have not. We also compare the
      gynaecological side effects, in particular the infectious symptoms, following an
      induced abortion, according to the abortion technique, medical and surgical, in
      the year after the abortion. PATIENTS AND METHODS: A representative sample of
      2863 women, aged 18 to 44, was interviewed by telephone between September 2000
      and January 2001. Of these women, 401 declared an abortion in the last 5 years.
      Analysis of the gynaecological side effects according to the abortion technique
      was performed among the 199 women who terminated their pregnancy before the 8th
      week of amenorrhoea. RESULTS: Women with a history of induced abortion had a
      higher sexual risk profile than those with no such history. They also more
      frequently reported genital infectious symptoms. The comparison between medical
      and surgical abortions shows that women who had a medical abortion were more
      likely to report heavy and prolonged bleeding. On the contrary, we found no
      difference of infectious symptoms between the two techniques. DISCUSSION AND
      CONCLUSION: Our study does not support the idea of a reduction of infectious
      complications related to medical as opposed to surgical abortions. However, given
      the rapid diffusion of medical abortion, it seems important to carry on the
      investigations on the side effects related to medical abortions, in order to
      prevent them if necessary.

PMID- 15848083
TI  - [Age fifty and menopause. Complaints expressed and unexpressed by women.
      Practitioners' perception and therapeutic impact].
AB  - OBJECTIVE: Identification of symptoms appearing at the time of menopause, and
      evaluation of their spontaneous expression level, connection with menopause and
      therapeutic impact. POPULATION AND METHOD: Opinion survey carried out with 1229
      French gynaecologists. RESULTS: The classical symptoms of menopause (hot flushes,
      night sweats, dry vagina) are spontaneously expressed by women. Atypical symptoms
      of menopause (sexual, relational and neuropsychological disorders) are less
      expressed. They are considered by practitioners as related to menopause, but less
      than classical symptoms. The ageing symptoms (muscle loss, joint pain, skin
      ageing, and disappearance of phantasms...) are scarcely expressed by women and
      connected with menopause by a minority of gynaecologists. The stronger the
      connection with menopause is, the more the symptom justifies a hormonal treatment
      of menopause. Thus, when classical symptoms are present, the hormonal treatment
      is almost always justified but it is less justified in case of atypical symptoms,
      and more disputable for the ageing symptoms. DISCUSSION AND CONCLUSION: Beyond
      the most evident signs of menopause, several other symptoms scarcely expressed by
      women can justify a hormonal treatment of menopause even when the connection with
      menopause is not demonstrated. Improvement of menopause treatment strategy
      requires taking into account all these symptoms, and a hormonal substitution that
      might be sometimes broader than the estrogenic therapy (androgenic, for example).

PMID- 15848084
TI  - [Vaginal evisceration. Report of a new case].
AB  - Vaginal evisceration is rare and most commonly found in postmenopausal women. We
      report the case of a postmenopausal woman due to ruptured enterocele. Surgical
      treatment was done through a midline laparotomy and consisted of bowel resection
      with primary anastomosis and vaginal vault suture repair. Risk factors for this
      rare clinical entity are discussed along with the different therapeutic options.

PMID- 15848085
TI  - [Psychological adjustment of stereotactic breast biopsy instrumentation
      procedures: about 73 cases].
AB  - OBJECTIVE: The aim of the study was to investigate patients' perceptions after
      stereotactic breast biopsy instrumentation, after both procedure and results.
      PATIENTS AND METHOD: From 1 March 2002 to 31 March 2003, a questionnaire (Likert
      response type) on stress was given to 73 patients who had breast biopsies
      procedures, the first time at the end of the procedure (T1) and then after the
      histological diagnosis (T2). RESULTS: The questionnaire was validated through
      analysis of principal component with Varimax rotation. Three factors were
      identified: procedure, quality of life, information and perception after biopsy.
      Responses were analysed with Chi-square. Two groups of women were identified, the
      first group (G1) corresponding to patients with a benign diagnosis (N=32) and the
      second group (G2) to patients with malignant diagnosis (N=32). Only the
      "procedure" factor was different at T1 and T2 (P=0.022). Compression was found to
      be painful: 11% at T1 versus 21% at T2. Women were disturbed by local anesthesia:
      26% at T1 versus 21% at T2. Biopsy was painful: 6% at T1 versus 13% at T2.
      Examination was too long: 24% at T1 versus 35% at T2. The procedure was
      discomfortable: 52% at T1 versus 54% at T2. Information satisfied patients in 90%
      cases. There was no statistically significant difference according to procedures
      and histological disease (P=0.357). DISCUSSION AND CONCLUSION: Information and
      medical empathy conditioned patients' perceptions. Patients tolerated the
      procedures well.

PMID- 15848086
TI  - [Angiogenesis and breast neoplasms. The pathologist's point of view].
AB  - Angiogenesis is an essential step of the tumoral growth and of the metastatic
      dissemination. It provides the nutriments necessary to the tumor and by the
      direct contact of the lumen vessels, facilitates its metastatic extension. The
      activation implies a large number of different agents which closely interact with
      the extracellular matrix. The intra tumoral vessels constitute an irregular
      network with numerous shunts. Their wall is also abnormal, incompletely covered
      by pericytes, and their basal membrane is thin and fragmented, sometimes absent.
      These features are responsible for an increased permeability and despite the
      large number of vessels, deserve a less effective oxygenation. The hypoxia
      induced secondarily activates the synthesis of angiogenic factors. The
      pathologist receives today help from immunohistochemistry for the evaluation of
      angiogenesis. This means facilitates the detection of vessels by use of specific
      antibodies directed against the endothelial cells (CD31, CD34, fVIIIrag...). It
      also allows the quantification of vessels or "microvascular density". Its
      importance varies from one patient to another and for different areas of a same
      tumour, the "hot-spot" generally located at its periphery. Despite its
      heterogeneity and the complexity of mechanisms involved in the regulation, the
      microvascular density appears to be an independent prognostic factor for tumour
      of different histological types. Immunohistochemistry also permits the evaluation
      of different characteristics of vessels and the tumour such as the activators
      (VEGF, FGF...) or their specific receptors (VEGF-R). Such analysis is also
      important for the determination of the prognosis but appears more interesting for
      the selection of the antiangiogenic treatment. However, this step will require
      the standardization of the immunohistochemistry techniques and the implementation
      of an external quality control.

PMID- 15848087
TI  - [MRI of the pituitary gland: indications and results in gynaecology and in
      obstetrics].
AB  - MRI is the sole radiological examination to be obtained if abnormal menses,
      galactorrhea or anovulation evokes the diagnosis of prolactinoma. Nevertheless,
      iatrogenic hyperprolactinemia or presence of big prolactin has to be ruled out
      before MRI is asked for. MRI of the pituitary gland must be technically optimal;
      analysis of the images has to be directed by clinical and biological data.

PMID- 15848088
TI  - [How I perform...an embryo transfer].

PMID- 15848089
TI  - [How I perform...an amniocentesis].

PMID- 15848090
TI  - [How to install an implantable site for chemotherapy through the cephalic vein].

PMID- 15848091
TI  - [For or against continuing oral contraceptives up to age 50].

PMID- 15848092
TI  - [For continuing to prescribe oral contraceptives up to age 50].

PMID- 15848093
TI  - [Against continuing oral contraceptives up to age 50].

PMID- 15848094
TI  - [The Anaes recommendations for good practice: early discharge after delivery.
      Conditions for proposing early homecoming (May 2004)].

PMID- 15848095
TI  - [Experts? Reflections on the decision of the Anaes recommendations to refuse
      breast cancer screening of women at the age of 50].

PMID- 15848100
TI  - Synthesis of dinitrochalcones by using ultrasonic irradiation in the presence of
      potassium carbonate.
AB  - The synthesis of dinitrochalcones was studied by using ultrasonic irradiation in
      the presence of potassium carbonate as a catalyst, which provided a conventional
      procedure with the advantages of a short reaction period and as high as 90%
      product yield.

PMID- 15848101
TI  - Ultrasonic cavitation in thin liquid layers.
AB  - The generation of ultrasonic cavitation in a thin liquid layer trapped between a
      large radiating surface and a hard reflector and bounded laterally by a gas
      liquid interface is investigated. The theoretical analysis predicts that a large
      amplification of the acoustical pressure is obtained with this configuration.
      Experiments are conducted by driving the layer with horn-type transducers having
      a large emitting surface. Ultrasonic cavitation is obtained in a broad frequency
      range at low input intensity due to the amplification effect. Erosion tests on
      metallic foils demonstrate the existence of a region of intense cavitation
      activity which can be localised by controlling the input intensity.

PMID- 15848102
TI  - Electroreduction of N-methylphthalimide in room temperature ionic liquids under
      insonated and silent conditions.
AB  - The selective electroreduction N-methylphthalimide to 3-hydroxy-2-methyl
      isoindolin-1-one has been performed in ionic liquids using phenol as a proton
      donor under silent and ultrasonic conditions. A significant increase in the rate
      of electroreduction is shown using ultrasonic activation and in addition high
      current efficiencies were observed. Some decomposition of the ionic liquid was
      found to have occurred under exposure to ultrasound.

PMID- 15848103
TI  - Ultrasonic activated efficient method for the cleavage of epoxides with aromatic
      amines.
AB  - An improved protocol for the cleavage of epoxides with aromatic amines in the
      presence of FeCl3 promoted by ultrasonic irradiation. This new methodology
      provides excellent yields in short reaction times (15-25 min) at room
      temperature.

PMID- 15848104
TI  - Reduction of arylnitro compounds to azoarenes and/or arylamines by Al/NaOH in
      methanol under ultrasonic conditions.
AB  - Arylnitro compounds are reduced to the corresponding azoarenes and/or arylamines
      by aluminium metal in the presence of sodium hydroxide in methanol in high yields
      under influence of power ultrasound (35 kHz) at 25 degrees C.

PMID- 15848105
TI  - Ultrasound promoted regioselective synthesis of beta-iodoethers from olefin-I2
      alcohol.
AB  - Regioselective synthesis of beta-iodoethers in high yields by sonicating alkene
      and alcohol in the presence of iodine in a bath at 35 kHz is reported.

PMID- 15848106
TI  - Dynamics of cavitational bubbles and design of a hydrodynamic cavitational
      reactor: cluster approach.
AB  - In the present work, a cavity cluster of predetermined size has been considered
      to study the bubble dynamics in the hydrodynamic cavitation reactor. The effect
      of different operating and system parameters on the cavitational intensity has
      been numerically investigated. The yield of any cavitationally induced
      physical/chemical transformations depends not only on the collapse pressure of
      the cavities but also on the active volume of cavitation within the reactor.
      Empirical correlations have been developed to predict the collapse pressure and
      the active volume of cavitation as a function of different operating parameters
      based on the bubble dynamics studies. Recommendations are made for designing a
      cavitational reactor on the basis of the proposed empirical correlations. This
      work is a first step towards the designing and optimization of hydrodynamic
      cavitational reactor with cluster approach.

PMID- 15848107
TI  - Investigation of induction of air due to ultrasound source in the sonochemical
      reactors.
AB  - A detailed investigation into the phenomena of induction of air using a novel
      arrangement of the ultrasonic horn (tip is located just above the liquid surface)
      has been made with the quantification of the extent of induction in terms of the
      air entrainment rate and the gas-liquid mass transfer coefficient for the
      transfer of air into the system. The measurement of air entrainment rate was
      found to be quite difficult and hence focus was kept on the quantification in
      terms of the gas-liquid mass transfer coefficient. The effect of ultrasonic power
      dissipation and type of the liquid medium (water, sodium chloride and sodium
      laruyl sulphate [surfactant] solution) on the mass transfer coefficient has been
      studied and correlations have been developed for the prediction of the same.
      Comparison with the mechanically agitated surface aerators has enabled us to
      understand the controlling mechanism in the induction and subsequent distribution
      of the air i.e. turbulence or convective motion. The present work should open an
      entirely new field of research in the area of design of sonochemical gas-liquid
      reactors operating possibly as a combination of gas-inducing reactors and
      cavitational reactors.

PMID- 15848108
TI  - Effect of various sono-oxidation parameters on the removal of aqueous 2,4
      dinitrophenol.
AB  - The influences of ultrasonic output intensity, solution pH, H2O2 concentration
      and the addition of Fenton reagent on the degradation of 2,4-dinitrophenol (DNP)
      under ultrasonic irradiation were investigated. It was observed that the
      degradation of DNP fitted pseudo-first-order dynamics under our experimental
      conditions. Increasing the ultrasonic output intensity increased the degradation
      efficiency of DNP and low pH favored the ultrasonic degradation of DNP. The
      addition of H2O2 enhanced the ultrasonic degradation efficiency of DNP. The
      further addition of Cu2+, however, hindered the degradation of DNP. In contrast,
      sono-oxidation treatment in combination with FeSO4/H2O2 showed a synergistic
      effect for DNP degradation.

PMID- 15848109
TI  - Influence of ultrasound treatment on accessibility and regioselective oxidation
      reactivity of cellulose.
AB  - Cellulose fibers were treated with ultrasound in order to improve the
      accessibility and the reactivity of cellulose. The influence of ultrasound
      treatment on changes of morphology structure, accessibility and oxidation
      reactivity of cellulose with sodium periodate were discussed. The results
      revealed an increase in cellulose's accessibility in terms of water retention
      value (WRV) with increasing ultrasound treatment time, corresponding to 73.0%,
      75.6%, 80.8%, 98.7% and 119.0% after treated for 0, 90, 180, 360 and 720 s,
      respectively. Furthermore, the regioselective oxidation reactivity of cellulose
      with sodium periodate was also successfully improved by the ultrasound treatment.
      However, no significant changes in crystallinity of cellulose were noted after
      ultrasound treatment. The oxidized products dialdehyde cellulose (DAC) was
      further characterized by means of FTIR, X-ray diffraction and SEM.

PMID- 15848110
TI  - Synthesis of 1,1-disubstituted-2,6-diarylcyclohexane-4-ones catalyzed by KF/basic
      Al2O3 under ultrasound.
AB  - 1,1-Disubstituted-2,6-diarylcyclohexane-4-ones have been synthesized via double
      Michael addition of 1,5-diaryl-1,4-pentadien-3-one with various active methylene
      compounds such as dimethyl malonate, diethyl malonate, methyl cyanoacetate and
      ethyl cyanoacetate catalyzed by KF/basic alumina under ultrasound irradiation to
      give good yields within a short time.

PMID- 15848111
TI  - Determination of pesticides in honey by ultrasonic solvent extraction and thin
      layer chromatography.
AB  - A rapid method for quantitative determination of atrazine and simazine in honey
      samples was investigated. The procedure was based on the extraction of pesticides
      by sonication with benzene:water = 1:1 (v/v) mixture, thin-layer chromatographic
      separation and quantification by CAMAG Video Documentation system in conjunction
      with the Reprostar 3. The extraction procedure was optimized with regard to the
      amount of solvent, duration of sonication and the number of extraction steps. The
      apparent recovery of pesticides from honey was 92.3 +/- 2.4 for atrazine and 94.2
      +/- 2.8 for simazine, when they were extracted in three steps for 20 min using 20
      ml of solvent. Ultrasonic solvent extraction was compared with traditional shake
      flask extraction method.

PMID- 15848112
TI  - Enrichment of surfactant from its aqueous solution using ultrasonic atomization.
AB  - Dilute aqueous solutions of dodecyl-benzenesulfonic acid sodium salt (DBS-Na) and
      polyoxyethylenenonylphenyl ethers (PONPEs) were ultrasonically atomized. The
      surfactants were concentrated in collected mist droplets. The enrichment ratio
      increased with decreasing surfactant concentration. Depending on the surfactant's
      molecular weight and affinity to water, different enrichment ratio was observed
      in the range of low feed concentrations. For anionic surfactant, DBS-Na, the
      enrichment ratio was significantly improved by KCl addition and a peak appeared
      on the plot of the ratio against KCl concentration. Addition of NaCl or CaCl2 .
      2H2O to the surfactant solution also enhanced the enrichment ratio; however, the
      effect was relatively small. Such behaviors of the ratio were interpreted as
      enhanced interfacial adsorption of the surfactant and a lack of supply of
      surfactant monomers from liquid bulk because of slow breaking of surfactant
      micelles. Time required for collecting an amount of mist was also observed. Among
      the three salt systems, the time for KCl system was twice as long as others. This
      fact suggested that the formation of smaller droplets in KCl system.

PMID- 15848113
TI  - Ultrasound enhances liposome-mediated gene transfection.
AB  - Previous studies have shown that some series of liposomes, usually containing
      cationic lipids, are useful tools for gene introduction into cells. To
      investigate the effect of ultrasound (US) on liposome-mediated transfection,
      three types of liposomes (designated L1, L2 and L3, in the order of increasing
      transfection efficiency) containing O,O'-ditetradecanoyl-N-(alpha
      trimethylammonioacetyl) diethanolamine chloride,
      dioleoylphosphatidylethanolamine, and/or cholesterol at varying ratios, were used
      in this study. HeLa cells were treated with liposome-DNA complexes containing
      luciferase genes for 2 h before sonication. Optimal US condition for the
      enhancement was determined to be 0.5 W/cm2, 1 MHz continuous wave for 1 min and
      was above threshold for inertial cavitation based on EPR detection of free
      radicals. Luciferase expressions 24 h after the treatments were significantly
      increased by sonication to 2.4 fold with L1, and 1.7 fold with L2. However, with
      L3, which showed the highest level of expression among the liposomes, significant
      but minimal enhancement was observed when sonication was done 15 min after the
      DNA-L3 treatment, suggesting that efficiency of the liposome also determines the
      proper timing for sonication. The 2 h pre-sonication incubation with liposome-DNA
      complexes for L1 and L2 (30 min for L3) required to attain enhancement, suggests
      that US works to enhance transfection only after cells had enough DNA uptake.

PMID- 15848114
TI  - Sonochemical removal of trihalomethanes from aqueous solutions.
AB  - In this research, ultrasound irradiation was employed to degrade the
      trihalomethanes, THMs: CHCl3, CHBrCl2, CHBr2Cl, CHBr3, and CHI3. The kinetics
      reaction rates and removal efficiencies of the THMs compounds, as a sole
      component in the aqueous solutions, were studied. Batch experiments were
      conducted at an ultrasonic frequency of 20 kHz and acoustic intensity of 3.75
      W/cm2. The first-order degradation rate constants and the sonolysis efficiencies
      followed the decreasing order of CHCl3 > CHBrCl2 > CHBr2Cl > CHBr3 > CHI3. Up to
      100% of the CHCl3 was removed, while only 60% of the CHI3 was sonodegraded, after
      180 min sonication. The THMs vapor pressure was found to be the most important
      parameter affecting the sonodegradation kinetics and efficiency, while the bond
      dissociation energy and hydrophilic/hydrophobic characteristics of the THMs
      compounds were found to be of secondary importance.

PMID- 15848115
TI  - The two-component cell lysis genes holWMY and lysWMY of the Staphylococcus
      warneri M phage varphiWMY: cloning, sequencing, expression, and mutational
      analysis in Escherichia coli.
AB  - From the genome library of Staphylococcus warneri M, the two successive cell
      lysis genes (holWMY and lytWMY) were cloned and characterized. The lytWMY gene
      encoded a protein (LysWMY), whose calculated molecular mass and pI were 54 kDa
      and 8.95, respectively. When overproduced in Escherichia coli, lysWMY directed a
      protein of 45 kDa (smaller than the predicted molecular mass), having N-terminal
      13 residues identical with those predicted from DNA. Comparative analysis
      revealed that LysWMY significantly resembles the putative N-acetylmuramoyl-L
      alanine amidases encoded by the staphylococcal phages phi11, 80 alpha, and Twort.
      Examination of modular organization of LysWMY identified three putative domains
      CHAP (for D-alanyl-glycyl endopeptidase), amidase (L-muramoyl-L-alanine amidase),
      and SH3 (cell wall recognition). Gene knockout analysis revealed that each of the
      two domains of CHAP and amidase was responsible for cell-lytic activity on a
      zymogram gel. Site-directed mutation of Cys29Ala, His92Ala, or Asn114Ala in the
      CHAP domain substantially reduced cell-lytic activity, suggesting that this Cys
      His-Asn triad is crucial for the enzymatic function. On the other hand, the
      holWMY gene encoded a protein (HolWMY) with molecular mass and pI of 16 kDa and
      4.36; this protein contained two potential transmembrane helices, resembling
      other predicted holins (a cytoplasmic membrane-disrupting protein) encoded by the
      S. aureus phage, phi11, 80 alpha, and Twort. Upon mitomycin C exposure of S.
      warneri M, a prophage (phiWMY) was induced and the virion was examined under
      electron microscopy. PCR amplification and sequencing revealed the presence of
      the holWMY-lysWMY genes in the phage genome.

PMID- 15848116
TI  - Molecular evolution of growth hormone gene family in old world monkeys and
      hominoids.
AB  - Growth hormone is a classic molecule in the study of the molecular clock
      hypothesis as it exhibits a relatively constant rate of evolution in most
      mammalian orders except primates and artiodactyls, where dramatically enhanced
      rate of evolution (25-50-fold) has been reported. The rapid evolution of primate
      growth hormone occurred after the divergence of tarsiers and simians, but before
      the separation of old world monkeys (OWM) from new world monkeys (NWM).
      Interestingly, this event of rapid sequence evolution coincided with multiple
      duplications of the growth hormone gene, suggesting gene duplication as a
      possible cause of the accelerated sequence evolution. Here we determined 21
      different GH-like sequences from four species of OWM and hominoids. Combining
      with published sequences from OWM and hominoids, our analysis demonstrates that
      multiple gene duplications and several gene conversion events both occurred in
      the evolutionary history of this gene family in OWM/hominoids. The episode of
      recent duplications of CSH-like genes in gibbon is accompanied with rapid
      sequence evolution likely resulting from relaxation of purifying selection. GHN
      genes in both hominoids and OWM are under strong purifying selection. In
      contrast, CSH genes in both lineages are probably not. GHV genes in OWM and
      hominoids evolved at different evolutionary rates and underwent different
      selective constraints. Our results disclosed the complex history of the primate
      growth hormone gene family and raised intriguing questions on the consequences of
      these evolutionary events.

PMID- 15848117
TI  - Prognostic indicators estimated by (99m)Tc-GSA in acute liver damage.
AB  - A prognostic estimation formula of acute liver damage was evaluated by using
      clinical data and technetium-99m-diethylenetriaminepentaacetic acid-galactosyl
      human serum albumin ((99m)Tc-GSA) scintigraphy in order to determine operability
      for orthotopic liver transplantation (OLT). Forty-six patients hospitalized for
      acute liver damage were divided into survival (n=35) and non-survival (n=11)
      groups. Univariate and multivariate analyses were used to identify significant
      factors that affected prognosis. Logistic regression analysis was performed to
      predict prognosis with effective factors. Ten independent factors with
      significant differences were identified and further analyzed for significance by
      logistic regression analysis. Among the 10 factors, age and LHL15/HH15 were
      identified as having meaningful differences for predicting convalescence. The
      following formula was developed: A negative value for R indicates non-survivals,
      and a positive value indicates survivals. The mortality rate was calculated
      as=1/(1+e(R)). The sensitivity was 0.909, specificity was 1.000, and accuracy was
      0.978. The reliability of this formula was as good as that of another formula
      presented previously by the Intractable Liver Diseases Study Group of Japan. The
      use of (99m)Tc-GSA for estimating the prognosis of acute liver damage is useful,
      especially before the onset of hepatic encephalopathy.

PMID- 15848118
TI  - Doxapram stimulates the carotid body via a different mechanism than hypoxic
      chemotransduction.
AB  - To determine if doxapram stimulates the carotid body through the same mechanism
      as hypoxia, we compared the effects of doxapram and hypoxia on isolated-perfused
      carotid bodies in rabbits. Doxapram stimulated the carotid body in a dose
      dependent manner. In Ca(2+)-free solution, neither doxapram nor hypoxia
      stimulated the carotid body. Although, doxapram had an additive effect on the
      carotid body chemosensory response to hypercapnia, a synergistic effect was not
      observed. Also, we investigated the various K(+) channel activators on the
      response to doxapram and hypoxia: pinacidil and levcromakalim as ATP-sensitive
      K(+) channel activators; NS-1619 as a Ca(2+)-sensitive K(+) channel activator;
      and halothane as a TASK-like background K(+) channel activator. The hypoxic
      response was partially reduced by halothane only, while pinacidil, levcromakalim
      and NS-1619 had no effect. Interestingly, the effect of doxapram was partially
      inhibited by NS-1619. Neither pinacidil nor levcromakalim affected the
      stimulatory effect of doxapram. We conclude that doxapram stimulates the carotid
      body via a different mechanism than hypoxic chemotransduction.

PMID- 15848119
TI  - L-arginine's effect on the hypoxia-induced release of acetylcholine from the in
      vitro cat carotid body.
AB  - NO is known to reduce the hypoxia-induced increase in carotid body neural
      activity (CBNA). Acetylcholine (ACh), a known excitatory transmitter in the cat
      carotid body (CB), is released during hypoxia. This study addressed the impact of
      an NO precursor on ACh release during hypoxia. Both CBs from nine cats were
      prepared for incubation, then inserted into a medium and bubbled with three
      consecutive gas mixtures, hyperoxic, hypoxic, and a final hyperoxic mixture. This
      series of exposures was performed in the absence of L-arginine, followed by the
      three exposures in a 1mM L-arginine medium, and followed, thirdly, in a 10mM L
      arginine medium. L-Arginine significantly attenuated the hypoxia-induced release
      of ACh. Two post-arginine procedures suggested strongly that the reduction in the
      ACh release was not due to a gradual exhaustion of carotid body ACh stores over
      the course of the experiment. The data are consistent with those reports showing
      that NO donors and precursors reduce the hypoxia-induced increase in CBNA, and
      further support a role for ACh in the hypoxia-induced increase in CBNA.

PMID- 15848120
TI  - An astrocyte toxin influences the pattern of breathing and the ventilatory
      response to hypercapnia in neonatal rats.
AB  - Recent in vitro data suggest that astrocytes may modulate respiration. To examine
      this question in vivo, we treated 5-day-old rat pups with methionine sulfoximine
      (MS), a compound that alters carbohydrate and glutamate metabolism in astrocytes,
      but not neurons. MS-treated pups displayed a reduced breathing frequency (f) in
      baseline conditions relative to saline-treated pups. Hypercapnia (5% CO(2))
      increased f in both groups, but f still remained significantly lower in the MS
      treated group. No differences between treatment groups in the responses to
      hypoxia (8% O(2)) were observed. Also, MS-treated rats showed an enhanced
      accumulation of glycogen in neurons of the facial nucleus, the nucleus ambiguus,
      and the hypoglossal nucleus, structures that regulate respiratory activity and
      airway patency. An altered transfer of nutrient molecules from astrocytes to
      neurons may underlie these effects of MS, although direct effects of MS upon
      neurons or upon peripheral structures that regulate respiration cannot be
      completely ruled out as an explanation.

PMID- 15848121
TI  - Oxygen and life span: chronic hypoxia as a model for studying HIF-1alpha, VEGF
      and NOS during aging.
AB  - To test if oxygen sensitive mechanisms are affected by hypoxia, we studied
      hypoxia inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor
      (VEGF) and inducible nitric oxide synthase (iNOS) expression by
      immunohistochemical analysis in young and old rat carotid bodies (CBs) using
      hypoxia as a model for modulating aging. Four groups of male age-matched Wistar
      rats (3 and 24 months) were used. Two groups were kept in room air, and two
      groups were kept under chronic intermittent hypoxia for 12 days. In aged carotid
      body and in hypoxia the increased expression of HIF-1alpha, VEGF, iNOS is less
      evident as compared to the young one. Electron microscopy sections showed a
      reduced mitochondrial number and area in the aged CBs and during hypoxia. Less
      responsiveness to hypoxia could be evidenced in the aged rats as compared to the
      young rats, suggesting an age dependency of the oxygen sensitive mechanisms.

PMID- 15848122
TI  - The Valsalva manoeuvre--cardiovascular effects and performance technique: a
      critical review.
AB  - Variations in the technique of the Valsalva manoeuvre (VM) have been shown to
      greatly influence the pattern of cardiovascular response (CVR) to the test. Intra
      strain tachycardia, post-strain bradycardia, Valsalva ratio, and baroreflex
      sensitivity decrease in proportion to an increase in lung volume and a decrease
      in strain pressure at VM. In conditions of completely expanded lungs and low
      strain pressure many subjects reveal an intra-strain bradycardic response to VM
      instead of the usual tachycardic one. Intra-strain arterial hypotension and post
      strain hypertension decrease with decrease in strain pressure. The changes in
      heart rate and blood pressure during an expiratory VM are greater than the
      responses observed during completition of an inspiratory VM. The rate of the deep
      inspiration prior to strain has an impact particularly on phase I of the VM. The
      magnitude of the CVR correlates with the strain duration, particularly at high
      levels of strain pressure, and depends on the baseline level of the
      cardiovascular parameters and their variations. The paper discusses the possible
      mechanisms of different CVRs to variations in the technique of the VM. Some
      practical recommendations are suggested.

PMID- 15848123
TI  - Localized morphometric deformations of small airways and alveoli in intact mouse
      lungs under quasi-static inflation.
AB  - Localized morphometric deformations of small airways and alveoli during
      respiration have several biomechanical and physiological implications. We
      developed fast synchrotron radiation CT system to visualize the small airways and
      alveoli of an intact mouse lung without fixation and dehydration, and analyzed
      their localized morphometric deformations between functional residual capacity
      (FRC) and total lung capacity (TLC). The maximum resolution of 32.6lp/mm at the
      5% modulation transfer function level can be achieved with 11.8-microm voxels and
      7-min scanning. Compared with the values at FRC, the diameter and length for
      smaller airways (diameter at FRC <200 microm) increased by 68.8% and 29.5%
      (averaged value), and those for larger airways (diameter at FRC >400 microm)
      increased by 45.2 and 22.9% (averaged value), at TLC. Moreover we defined the
      volume behavior as the percentage of airway volume at FRC for TLC. The volume
      behavior for the small airways was not similar to that of the lung volume. These
      results indicated that all airways did not behave homogenously.

PMID- 15848124
TI  - Monitoring pulse oximetry via radiotelemetry in freely-moving lambs.
AB  - This study was aimed at validating the use of a custom-made wireless pulse
      oximeter in freely moving lambs, using radiotelemetry transmission. First,
      measurements obtained simultaneously using the new, wireless oximeter and a
      standard commercially-available pulse oximeter (Nonin 8500) were compared in five
      lambs during 5min episodes of normoxia, hypoxia and hyperoxia. Correlation
      between the two oximeters for both SpO(2) and heart rate was very good,
      regardless of oxygenation conditions. Secondly, the capabilities of our device
      were assessed during more than 45h of polysomnographic recordings in seven lambs.
      According to the plethysmographic pulse waveform, reliable SpO(2) values were
      obtained in more than 85% of recording time. Multiple decreases in SpO(2) were
      readily observed after spontaneous apneas in preterm lambs. It is concluded that
      our wireless pulse oximeter performs as reliably as a standard pulse oximeter for
      monitoring SpO(2) variations in lambs, and offers new perspectives for
      researchers interested in continuous monitoring of oxygenation throughout sleep
      stages and wakefulness.

PMID- 15848125
TI  - A discussion regarding the contribution of intrapulmonary gas mixing to O2
      isotope fractionation by respiration using experimental data for 36Ar and 40Ar.
AB  - We determined the argon (Ar) isotope ratio in samples of expired alveolar gas
      gathered during Ar washout from residual gas relative to this ratio in samples of
      expired alveolar gas gathered just before the beginning of this washout in 13
      young, healthy human subjects at rest. These data were determined for a limited
      number of breaths in early washout and were used to calculate the relative
      difference between the alveolar ventilations of (36)Ar and (40)Ar (Delta(rel)V
      (A)((36)Ar,(40)Ar)). Mean Delta(rel)V (A)((36)Ar,(40)Ar) amounted to 1.6 per
      thousand (S.D.=1.3 per thousand). This result was then used to discuss the
      contribution of intrapulmonary gas mixing by diffusion to oxygen isotope
      fractionation of alveolar gas by respiration. On the basis of our finding for
      Delta(rel)V (A)((36)Ar,(40)Ar) and further theoretical considerations we arrived
      at the conclusion that this contribution for subjects at rest is small (about 1
      per thousand) and that this contribution is negative irrespective of the level of
      exercise.

PMID- 15848126
TI  - Prolonged exposure to NT-3 attenuates cholinergic nerve-mediated contractions in
      cultured murine airways.
AB  - Chronic airway inflammation may induce subsequent airway hyper-responsiveness
      (AHR) including pathological alteration of neural activity. Asthmatic airways
      contain elevated levels of neurotrophin-3 (NT-3) and brain-derived neurotrophic
      factor (BDNF) albeit, their effect on neural activity is unclear. This study
      evaluates the effects of NT-3 and BDNF on nerve mediated airway contractions in
      vitro. Tracheal segments from BALB/c J mice were cultured for 4 days with NT-3 or
      BDNF. Responsiveness to electric field stimulation (EFS) was evaluated in organ
      bath and innervation patterns were examined by quantitative immunohistochemistry.
      In cultured segments the EFS-induced contractions were inhibited by tetrodotoxin
      or atropine. NT-3 reduced the EFS contractions in a concentration-dependent
      manner whereas BDNF had no effect. The amount of nerve fibers, found in
      conjunction with the tracheal smooth muscle, was similar in NT-3 treated and
      control segments. In conclusion, NT-3 attenuates cholinergic nerve-mediated
      contractions of airway in vitro. Considering the elevated levels of NT-3 found in
      asthmatic airways, the findings imply a protective role of NT-3 in AHR.

PMID- 15848127
TI  - Muscle blood flow-O2 uptake interaction and their relation to on-exercise
      dynamics of O2 exchange.
AB  - A computer model was developed to provide a theoretical framework for
      interpreting the dynamics of muscle capillary O(2) exchange in health and
      disease. We examined the effects of different muscle oxygen uptake (V O(2m)) and
      CvO(2) profiles on muscle blood flow (Q (m)) kinetics (Q (m)=V O(2m)/[CaO(2)
      CvO(2)]). Further, we simulated V O(2m) and Q (m) responses to predict the CvO(2)
      profile and the underlying dynamics of capillary O(2) exchange (CvO(2)=CaO(2)-V
      O(2m)/Q (m)). Exponential equations describing V O(2m), CvO(2) and Q (m)
      responses in vivo were used in the simulations. The results indicated that Q (m)
      kinetics were relatively insensitive to CvO(2) parameters, but directly
      associated with V O(2m) kinetics. The biphasic Q (m) response produced a
      substantial fall in CvO(2) within the first 15-20s of the exercise transition
      (phase 1 of Q (m)). These results revealed that the main determinant of CvO(2)
      (or O(2) extraction) kinetics was the dynamic interaction of Q (m) and V O(2m)
      kinetics during phase 1 of Q (m).

PMID- 15848128
TI  - Enhanced alveolar growth and remodeling in Guinea pigs raised at high altitude.
AB  - To examine the effects of chronic high altitude (HA) exposure on lung structure
      during somatic maturation, we raised male weanling guinea pigs at HA (3800m) for
      1, 3, or 6 months, while their respective male littermates were simultaneously
      raised at low altitude (LA, 1200m). Under anaesthesia, airway pressure was
      measured at different lung volumes. The right lung was fixed at a constant airway
      pressure for morphometric analysis under light and electron microscopy. In
      animals raised at HA for 1 month, lung volume, alveolar surface area and alveolar
      capillary blood volume (V(c)) were elevated above LA control values. Following 3
      6 months of HA exposure, increases in lung volume and alveolar surface area
      persisted while the initial increase in V(c) normalized. Additional adaptation
      occurred, including a higher epithelial cell volume, septal tissue volume and
      capillary surface area, a lower alveolar duct volume and lower harmonic mean
      diffusion barrier resulting in higher membrane and lung diffusing capacities.
      These data demonstrate enhanced alveolar septal growth and progressive acinar
      remodeling during chronic HA exposure with long-term augmentation of alveolar
      dimensions as well as functional compensation in lung compliance and diffusive
      gas transport.

PMID- 15848129
TI  - Heterogeneity of brainstem blood flow response to hypoxia in the anesthetized
      rat.
AB  - Cerebral blood flow is strictly regulated during hypoxic stress. Because of the
      preponderant role of the brainstem in cardiorespiratory controls, blood flow
      response to hypoxia is stronger in this region than in the cortex. However, the
      brainstem is made up of various regions which differ in their responsiveness to
      chemical stimuli. The objective of this study was to evaluate the distribution of
      blood flow during hypoxia using microsphere deposition methods in three brainstem
      regions containing key structures in cardiorespiratory controls: the nucleus
      tractus solitarus (NTS), the ventral respiratory groups (VRG) and the pontine
      respiratory groups (PRG). Microsphere injections were made during normoxia
      (FIO2=0.21) and after 15 min of hypoxia (FIO2=0.21). Based on this index, blood
      flow increase during hypoxia was higher in the VRG than in the dorsal part of the
      brainstem, containing the NTS and the PRG (P=0.002, n=10). These results suggest
      that blood flow response to hypoxia favours O(2) delivery in brainstem regions
      involved in respiratory rhythm generation.

PMID- 15848130
TI  - A new insight into mercurized hemoglobin aggregation mechanism.
AB  - Coagulation of bovine oxyhemoglobin in the presence of mercuric acetate in
      concentrations within a range including concentrations exceeding those required
      to block the single pair of thiol groups of the protein has been investigated in
      Tris-acetate buffer. The values of initial coagulation rate plotted against
      mercury-to-hemoglobin molar ratio give curves exhibiting a clear break points at
      ratios corresponding to full blocking of the mentioned thiol groups. Larger
      amounts of mercury reagents producing enhanced protein coagulation effect depend
      approximately quadratically on the mercury concentration. Interaction of the
      excess mercuric ions with some mercury-binding sites located on or near the dimer
      dimer contact surfaces of the protein producing stronger coagulation effect is
      suggested.

PMID- 15848131
TI  - Biochemical characterization of recombinant acetyl xylan esterase from
      Aspergillus awamori expressed in Pichia pastoris: mutational analysis of
      catalytic residues.
AB  - We engineered an acetyl xylan esterase (AwaxeA) gene from Aspergillus awamori
      into a heterologous expression system in Pichia pastoris. Purified recombinant
      AwAXEA (rAwAXEA) displayed the greatest hydrolytic activity toward alpha
      naphthylacetate (C2), lower activity toward alpha-naphthylpropionate (C3) and no
      detectable activity toward acyl-chain substrates containing four or more carbon
      atoms. Putative catalytic residues, Ser(119), Ser(146), Asp(168) and Asp(202),
      were substituted for alanine by site-directed mutagenesis. The biochemical
      properties and kinetic parameters of the four mutant enzymes were examined. The
      S119A and D202A mutant enzymes were catalytically inactive, whereas S146A and
      D168A mutants displayed significant hydrolytic activity. These observations
      indicate that Ser(119) and Asp(202) are important for catalysis. The S146A mutant
      enzyme showed lower specific activity toward the C2 substrate and higher thermal
      stability than wild-type enzyme. The lower activity of S146A was due to a
      combination of increased K(m) and decreased k(cat). The catalytic efficiency of
      S146A was 41% lower than that of wild-type enzyme. The synthesis of ethyl acetate
      was >10-fold than that of ethyl n-hexanoate synthesis for the wild-type, S146A
      and D168A mutant enzymes. However, the D202A showed greater synthetic activity of
      ethyl n-hexanoate as compared with the wild-type and other mutants.

PMID- 15848132
TI  - The role of tryptophan residues in the autoprocessing of prosubtilisin E.
AB  - Subtilisin E, a serine protease from Bacillus subtilis, requires an N-terminal
      propeptide for its correct folding. The propeptide is autocleaved and digested by
      the subtilisin domain upon proper folding. Here we investigated the individual
      roles of the three Trp residues within the subtilisin domain (Trp106, Trp113 and
      Trp241) on propeptide processing, enzymatic activity and stability of subtilisin.
      When the propeptide processing was examined by SDS-PAGE after refolding by rapid
      dilution, the mutation at either position Trp106 or Trp113 was found to
      significantly delay the propeptide processing, while the mutation at Trp241 had
      no effect. Far-UV circular dichroism (CD) spectra of the mutants revealed that
      the mutations at the three positions did not affect appreciably the alpha-helix
      content of subtilisin. Secondary structure thermal unfolding monitored by CD
      spectroscopy revealed that none of the tryptophan residues had any significant
      effect on the stability of mature subtilisin. The enzymatic activity measurements
      showed that only Trp106 plays a major role in the enzymatic activity of
      subtilisin E. These results demonstrate that both Trp106 and Trp113 play a
      specific role in propeptide processing and enzymatic activity, while Trp241 plays
      no considerable role on any of these activities.

PMID- 15848133
TI  - Proteome analysis of rat pancreas induced by pancreatectomy.
AB  - The previous study demonstrated that the streptozotocin (STZ)-induced diabetic
      mice can be cured by injecting the regenerating pancreatic extract (RPE) of the
      partially pancreatectomized Wistar-Kyoto rats. In this study, to characterize the
      complex pattern of protein expression in RPE, the proteins of altered expression
      level after the pancreatectomy were identified by 2-dimensional electrophoresis
      (2-DE) and mass spectrometry. Of 76 significantly up- or down-regulated protein
      spots, 61 were identified by MALDI-TOF/MS. Moreover, the whole RPE was
      fractionated into 4 groups using an anion-exchange chromatography and each
      fraction's cell proliferating activity was measured by MTT assay. Compared to the
      normal pancreatic extract, fraction 3 and 4 of RPE showed the maximal cell
      proliferating activity. On 2-DE of 3 and 4 fractions, a total of 10 spots, which
      are differentially expressed after the pancreatectomy, were identified by MS/MS.
      Of these identified proteins, Reg III which might be functionally associated with
      well known regenerating factor (Reg I) was found. Taken together, our results
      demonstrated that the differential protein expression associated with pancreas
      regeneration could be sought by 2-DE and mass spectroscopy and suggested that the
      pre-fractionation method combined with in vitro cell proliferation assay is
      effectively used to pinpoint the active components for pancreas regeneration.

PMID- 15848134
TI  - Ionisations within a subtilisin-glyoxal inhibitor complex.
AB  - Z-Ala-Pro-Phe-glyoxal (where Z is benzyloxycarbonyl) has been shown to be a
      competitive inhibitor of subtilisin with a K(i)=2.3+/-0.2 microM at pH 7.0 and 25
      degrees C. Using Z-Ala-Pro-[2-(13)C]Phe-glyoxal we have detected a signal at
      107.3 ppm by (13)C NMR, which we assign to the tetrahedral adduct formed between
      the hydroxy group of serine-195 and the (13)C-enriched keto-carbon of the
      inhibitor. The chemical shift of this signal is pH independent from pH 4.2 to 7.0
      and we conclude that the oxyanion pK(a)<3. This is the first observation of
      oxyanion formation in a reversible subtilisin-inhibitor complex. The inhibitor is
      bound as a hemiketal which is in slow exchange with the free inhibitor. Inhibitor
      binding depends on a pK(a) of approximately 6.5 in the free enzyme and on a
      pK(a)<3.0 when the inhibitor is bound to subtilisin. Protonation of the oxyanion
      promotes the disassociation of the inhibitor. We show that oxyanion formation
      cannot be rate limiting during catalysis and that subtilisin stabilises the
      oxyanion by at least 45.1 kJ mol(-1). We conclude that if the energy required for
      oxyanion stabilisation is utilised as binding energy in drug design it should
      make a significant contribution to inhibitor potency.

PMID- 15848135
TI  - An electrochemical investigation of hemoglobin and catalase incorporated in
      collagen films.
AB  - Collagen, an electrochemically inert protein, formed films on pyrolytic graphite
      (PG) electrodes, which provided a suitable microenvironment for heme proteins to
      transfer electron directly with the underlying electrodes. Hemoglobin (Hb) and
      catalase (Cat) incorporated in collagen films exhibited a pair of well-defined
      and quasi-reversible cyclic voltammetric peaks at around -0.35 V and -0.47 V (vs.
      SCE) in pH 7.0 buffers, respectively, characteristic of the protein heme
      Fe(III)/Fe(II) redox couples. UV-vis spectra showed that the heme proteins in
      collagen films retained their near-native conformations in the medium pH range.
      The results of scanning electron microscopy (SEM) demonstrated that the
      interaction between heme proteins and collagen made the morphology of dry protein
      collagen films different from the collagen films alone. The electrochemical
      parameters such as apparent heterogeneous electron transfer rate constant (k(s))
      and formal potential (E degrees ') of the films were estimated by using square
      wave voltammograms (SWV) and nonlinear regression analysis. The heme protein
      collagen film electrodes were also used to catalyze the reduction of nitrite,
      oxygen and hydrogen peroxide, indicating potential applications of the films for
      the fabrication of a new type of biosensor that does not use mediators.

PMID- 15848136
TI  - Action pattern of Fusarium moniliforme endopolygalacturonase towards pectin
      fragments: Comprehension and prediction.
AB  - The structures of complexes of Fusarium moniliforme endopolygalacturonase
      (endoPG) with non-methylated or partly methylated homogalacturonan fragments were
      modeled to identify the residues involved in substrate binding and to correlate
      the cleavage pattern with the experimental productive modes. The conformational
      space of the complex was extensively explored and malto- to hexo
      oligogalacturonates were modeled in the active cleft. To select the most highly
      probable productive complex for each oligomer between DP2 and 6, four energetic
      criteria were defined. Noteworthingly, the results were in accordance with the
      experimental results showing the mode of action of this enzyme towards un-methyl
      esterified oligogalacturonates. Furthermore, the amino-acid residues involved in
      the binding were confirmed by similar studies performed on other endoPGs. Then,
      the oligomers were gradually methyl-esterified at one or more positions and
      similar docking experiments were carried out. Markedly, the docking energies were
      not significantly modified by the methyl-esterification of the substrate and it
      is likely that the methyl-esterification of the substrate does not alter the mode
      of action of the enzyme. Finally, 1D sequence and 3D structure of the
      endopolygalacturonase of Aspergillus niger II, known to be strictly non-tolerant
      to methylesters, were compared with the sequence and structure of the tolerant F.
      moniliforme endopolygalacturonase to get to a structural comprehension of the
      tolerant-or not-behaviour of endoPGs with methyl-esterified pectins.

PMID- 15848137
TI  - Stochastic boundary molecular dynamics simulation of L-ribose in the active site
      of Actinoplanes missouriensis xylose isomerase and its Val135Asn mutant with
      improved reaction rate.
AB  - We used molecular dynamics simulations to study how a non-natural substrate, L
      ribose, interacts with the active site of Actinoplanes missouriensis xylose
      isomerase. The simulations showed that L-ribose does not stay liganded in the
      active site in the same way as D-xylose, in which the oxygens O2 and O4 are
      liganded to the metal M1. The oxygen O4 of L-ribose moved away from the metal M1
      to an upside down position. Furthermore, the distances of the carbons C1 and C2
      of L-ribose to the catalytic metal M2 were higher than in the case of D-xylose.
      These findings explain the extremely low reaction rate of xylose isomerase with L
      ribose. The mutation V135N close to the C5-OH of the substrate increased the
      reaction efficiency 2- to 4-fold with L-ribose. V135N did not affect the reaction
      with D-xylose and L-arabinose, whereas the reaction with D-glucose was impaired,
      probably due to a hydrogen bond between Asn-135 and the substrate. When L-ribose
      was the substrate, Asn-135 formed a hydrogen bond to Glu-181. As a consequence,
      O4 of L-ribose stayed liganded to the metal M1 in the V135N mutant in molecular
      dynamics simulations. This explains the decreased K(m) of the V135N mutant with L
      ribose.

PMID- 15848138
TI  - Characterization and study of a kappa-casein-like chymosin-sensitive linkage.
AB  - The present report is dealing with the identification, in various unrelated
      proteins, of protein fragments sharing local sequence and structure similarities
      with the chymosin-sensitive linkage surrounding the Phe-Met/Ile bond of kappa
      caseins. In all these proteins, this linkage is observed within an exposed beta
      strand-like structure, as also predicted for kappa-caseins. The structure of one
      of these fragments, included in glutamine synthetase, particularly superimposes
      well with the conformation observed for a chymosin inhibitor (CP-113972) within
      the complex it forms with chymosin and can be similarly accommodated by
      specificity pockets within the enzyme substrate binding cleft. The effect of the
      enzyme activity of chymosin was thus tested on glutamine synthetase. Chymosin cut
      the latter at the Phe-Met linkage, suggesting that this system may locally
      resemble the kappa-casein/chymosin complex.

PMID- 15848139
TI  - Apolipoprotein AI could be a significant determinant of epithelial integrity in
      rainbow trout gill cell cultures: a study in functional proteomics.
AB  - The freshwater fish gill forms a barrier against an external hypotonic
      environment. By culturing rainbow trout gill cells on permeable supports, as
      intact epithelia, this study investigates barrier property mechanisms. Under
      symmetrical conditions the apical and basolateral epithelial surfaces contact
      cell culture media. Replacing apical media with water, to generate asymmetrical
      conditions (i.e. the situation encountered by the freshwater gill), rapidly
      increases transepithelial resistance (TER). Proteomic analysis revealed that this
      is associated with enhanced expression of pre-apolipoprotein AI (pre-apoAI). To
      test the physiological relevance, gill cells were treated with a dose of 50
      microg ml(-1) human apolipoprotein (apoAI). This was found to elevate TER in
      those epithelia which displayed a lower TER prior to apoAI treatment. These
      results demonstrate the action of apoAI and provide evidence that the rainbow
      trout gill may be a site of apoAI synthesis. TER does not differentiate between
      the trans-cellular (via the cell membrane) and para-cellular (via intercellular
      tight junctions) pathways. However, despite the apoAI-induced changes in TER,
      para-cellular permeability (measured by polyethylene glycol efflux) remained
      unaltered suggesting apoAI specifically reduces trans-cellular permeability. This
      investigation combines proteomics with functional measurements to show how a
      proteome change may be associated with freshwater gill function.

PMID- 15848140
TI  - Detection of activity and mass spectrometric identification of mouse liver
      carboxylesterase and aldehyde dehydrogenase separated by non-denaturing two
      dimensional electrophoresis after extraction with detergents.
AB  - To examine the activities and identity of enzymes associated with organelles such
      as microsomes and mitochondria, proteins from mouse liver were extracted using
      the non-ionic detergents Nonidet P-40 (NP-40), polyoxyethylene sorbitan
      monooleate (Tween 80), polyoxyethylene isooctylphenyl ester (Triton X), n-octyl
      beta-D-glucoside (octyl glycoside) or anionic detergent sodium dodecylsulfate
      (SDS) after the removal of cytosolic proteins. The proteins extracted by
      detergents were separated by non-denaturing two-dimensional electrophoresis (2
      DE). The activities of esterase and aldehyde dehydrogenase were retained by non
      denaturing 2-DE after treatment with each non-ionic detergent, but the activities
      were reduced or lost when the proteins were extracted with more than 0.5% SDS.
      For proteomic analysis of the organelle-associated proteins in mouse liver,
      proteins were separated by non-denaturing 2-DE and were identified using
      electrospray ionization tandem mass spectrometry (ESI-MS/MS) after the proteins
      were solubilized by octyl glycoside, NP-40 and 0.1% SDS. Several organelle
      associated proteins such as carboxylesterase, aldehyde dehydrogenase, glucose
      regulated protein and HSP60 were identified. These results indicate that the
      activities and identity of detergent-soluble enzymes can be examined by this non
      denaturing 2-DE and mass spectrometry.

PMID- 15848141
TI  - Two consecutive aspartic acid residues conferring herbicide resistance in tobacco
      acetohydroxy acid synthase.
AB  - Acetohydroxy acid synthase (AHAS) catalyzes the first common step in the
      biosynthesis pathway of the branch chain amino acids in plants and
      microorganisms. A great deal of interest has been focused on AHAS since it was
      identified as the target of several classes of potent herbicides. In an effort to
      produce a mutant usable in the development of an herbicide-resistant transgenic
      plant, two consecutive aspartic acid residues, which are very likely positioned
      next to the enzyme-bound herbicide sulfonylurea as the homologous residues in
      AHAS from yeast, were selected for this study. Four single-point mutants and two
      double mutants were constructed, and designated D374A, D374E, D375A, D375E,
      D374A/D375A, and D374E/D375E. All mutants were active, but the D374A mutant
      exhibited substrate inhibition at high concentrations. The D374E mutant also
      evidenced a profound reduction with regard to catalytic efficiency. The mutation
      of D375A increased the K(m) value for pyruvate nearly 10-fold. In contrast, the
      D375E mutant reduced this value by more than 3-fold. The double mutants exhibited
      synergistic reduction in catalytic efficiencies. All mutants constructed in this
      study proved to be strongly resistant to the herbicide sulfonylurea Londax. The
      double mutants and the mutants with the D375 residue were also strongly cross
      resistant to the herbicide triazolopyrimidine TP. However, only the D374A mutant
      proved to be strongly resistant to imidazolinone Cadre. The data presented here
      indicate that the two residues, D374 and D375, are located at a common binding
      site for the herbicides sulfonylurea and triazolopyrimidine. D375E may be a
      valuable mutant for the development of herbicide-resistant transgenic plants.

PMID- 15848142
TI  - Analysis of ligation and DNA binding by Escherichia coli DNA ligase (LigA).
AB  - NAD(+)-dependent DNA ligases are essential enzymes in bacteria, with the most
      widely studied of this class of enzymes being LigA from Escherichia coli. NAD(+)
      dependent DNA ligases comprise several discrete structural domains, including a
      BRCT domain at the C-terminus that is highly-conserved in this group of proteins.
      The over-expression and purification of various fragments of E. coli LigA allowed
      the investigation of the different domains in DNA-binding and ligation by this
      enzyme. Compared to the full-length protein, the deletion of the BRCT domain from
      LigA reduced in vitro ligation activity by 3-fold and also reduced DNA binding.
      Using an E. coli strain harbouring a temperature-sensitive mutation of ligA, the
      over-expression of protein with its BRCT domain deleted enabled growth at the non
      permissive temperature. In gel-mobility shift experiments, the isolated BRCT
      domain bound DNA in a stable manner and to a wider range of DNA molecules
      compared to full LigA. Thus, the BRCT domain of E. coli LigA can bind DNA, but it
      is not essential for DNA nick-joining activity in vitro or in vivo.

PMID- 15848143
TI  - Mutation analysis of the human 5-lipoxygenase C-terminus: support for a
      stabilizing C-terminal loop.
AB  - Lipoxygenases contain prosthetic iron, in human 5-lipoxygenase (5LO) the C
      terminal isoleucine carboxylate constitutes one of five identified ligands. ATP
      is one of several factors determining 5LO activity. We compared properties of a
      series of 5LO C-terminal deletion mutants (one to six amino acid residues
      deleted). All mutants were enzymatically inactive (expected due to loss of iron),
      but expression yield (in E. coli) and affinity to ATP-agarose was markedly
      different. Deletion of up to four C-terminal residues was compatible with good
      expression and retained affinity to the ATP-column, as for wild-type 5LO. However
      when also the fifth residue was deleted (Asn-669) expression yield decreased and
      the affinity to ATP was markedly diminished. This was interpreted as a result of
      deranged structure and stability, due to loss of a hydrogen bond between Asn-669
      and His-399. Mutagenesis of these residues supported this conclusion. In the
      structure of soybean lipoxygenase-1, a C-terminal loop was pointed out as
      important for correct orientation of the C-terminus. Accordingly, a hydrogen bond
      appears to stabilize such a C-terminal loop also in 5LO.

PMID- 15848144
TI  - Proteomic analysis of complexes formed by human topoisomerase I.
AB  - Human topoisomerase I is a nuclear enzyme that catalyses DNA relaxation and
      phosphorylation of SR proteins. Topoisomerase I participates in several protein
      protein interactions. We performed a proteomic analysis of protein partners of
      topoisomerase I. Two methods were applied to proteins of the nuclear extract of
      HeLa cells: a co-immunoprecipitation and an affinity chromatography combined with
      mass spectrometry. Complexes formed by topoisomerase I with its protein partners
      were immunoprecipitated by scleroderma anti-topoisomerase I antibodies. To
      identify binding sites for the protein partners, baits corresponding to fragments
      of topoisomerase I were constructed and used in the affinity chromatography. The
      N-terminal domain and the cap region of the core domain appeared to be the main
      regions that bound proteins. We identified 36 nuclear proteins that were
      associated with topoisomerase I. The proteins were mainly involved in RNA
      metabolism. We found 29 new and confirmed 7 previously identified protein
      partners of topoisomerase I. More than 40% proteins that associate with the cap
      region contain two closely spaced RRM domains. Docking calculations identified
      the RRM domains as a possible site for the interaction of these proteins with the
      cap region.

PMID- 15848145
TI  - Crystallization of halorhodopsin from Halobacterium sp. shark.
AB  - The chloride-ion-pumping channel, halorhodopsin from Halobacterium sp. shark was
      detergent-solubilized and 3-D crystallized. Proteins were solubilized using the
      nonionic detergent n-octyl-beta-D-glucoside and were crystallized as thin-plate
      crystals with polyethylene glycol 4000 as a precipitant. The crystals belong to
      the space group P4(1)2(1)2 with unit-cell dimensions a=b=74.5 A and c=138.6 A.
      The diffraction pattern was slightly anisotropic. The best ordered crystal
      diffracted up to 3.3 A resolution along c axis with synchrotron radiation.

PMID- 15848146
TI  - P2Y2 nucleotide receptor up-regulation in submandibular gland cells from the
      NOD.B10 mouse model of Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is an autoimmune disease that specifically targets
      exocrine glands, including salivary glands, and results in an impairment of
      secretory function. P2Y(2) nucleotide receptors for extracellular ATP and UTP are
      up-regulated in response to stress or injury in a variety of tissues including
      submandibular glands (SMGs) [Ahn JS, Camden JM, Schrader AM, Redman RS, Turner
      JT. Reversible regulation of P2Y(2) nucleotide receptor expression in the duct
      ligated rat submandibular gland. Am J Physiol Cell Physiol 2000;279:C286-94; Hou
      M, Malmsjo M, Moller S, Pantev E, Bergdahl A, Zhai X-H, et al. Increase in
      cardiac P2X(1)- and P2Y(2)-receptor mRNA levels in congestive heart failure. Life
      Sci 1999;65:1195-206; Kishore BK, Wang Z, Rab H, Haq M, Soleimani M. Upregulation
      of P2Y(2) purinoceptor during ischemic reperfusion injury (IRI): possible
      relevance to diuresis of IRI. J Am Soc Nephrol 1998;9:581 (abstract); Koshiba M,
      Apasov S, Sverdlov V, Chen P, Erb L, Turner JT, et al. Transient up-regulation of
      P2Y(2) nucleotide receptor mRNA expression is an immediate early gene response in
      activated thymocytes. Proc Natl Acad Sci U S A 1997;94:831-6; Turner JT, Landon
      LA, Gibbons SJ, Talamo BR. Salivary gland P2 nucleotide receptors. Crit Rev Oral
      Biol Med 1999;10:210-24; Seye CI, Gadeau AP, Daret D, Dupuch F, Alzieu P, Capron
      L, et al. Overexpression of the P2Y(2) purinoceptor in intimal lesions of the rat
      aorta. Arterioscler Thromb Vasc Biol 1997;17:3602-10; Seye C, Kong Q, Erb L,
      Garrad RC, Krugh B, Wang M, et al. Functional P2Y(2) nucleotide receptors mediate
      uridine 5'-triphosphate-induced intimal hyperplasia in collared rabbit carotid
      arteries. Circulation 2002;106:2720-6]. OBJECTIVE: To assess whether P2Y(2)
      receptor expression is up-regulated in SMGs of the NOD.B10 mouse model of primary
      SS as compared to SMGs of normal C57BL/6 mice. DESIGN: SMG cells were isolated
      from normal C57BL/6 and diseased NOD.B10 mice. P2Y(2) receptor mRNA expression
      was determined by reverse transcription-polymerase chain reaction (RT-PCR) and in
      situ hybridization, whereas functional P2Y(2) receptor activity was analyzed by
      measuring UTP-induced increases in [Ca(2+)](i). RESULTS: In contrast to SMG cells
      from C57BL/6 mice, SMG cells from 4- to 19-week-old NOD.B10 mice exhibited
      increased P2Y(2) receptor mRNA localized to both ductal and acinar cell types.
      The levels of mRNA for other uridine nucleotide receptors, i.e., P2Y(4) and
      P2Y(6) receptors, showed no significant differences between SMG cells of C57BL/6
      and NOD.B10 mice, suggesting that only the P2Y(2) receptor was up-regulated in
      NOD.B10 mice. Moreover, P2Y(2) receptor activity in SMG cells from NOD.B10 mice
      increased with age (i.e., disease progression). CONCLUSION: P2Y(2) receptor up
      regulation in SMGs is associated with the SS phenotype in NOD.B10 mice, which
      encourages further attempts to determine the role of this pathway in the
      development of SS.

PMID- 15848147
TI  - Erosive effects of different acids on bovine enamel: release of calcium and
      phosphate in vitro.
AB  - The present study intended to investigate minimal erosive effects of different
      acids on enamel during short time incubation via determination of calcium and
      phosphate dissolution. Bovine enamel specimens were eroded for 1-5 min with eight
      different acids of pH 2, 2.3 and 3 (citric (CA), maleic (MA), lactic (LA),
      tartaric (TA), phosphoric (PA), oxalic (OA), acetic (AA) and hydrochloric acid
      (HCl)). Calcium (Ca) and phosphate (P) release were determined photometrically
      using arsenazo III (calcium) and malachite green (phosphate) as substrates. Each
      subgroup contained eight enamel specimens. Amount of titratable acid was
      determined for all acidic solutions. MA, LA, TA, AA and HCl caused linear release
      of Ca and P, PA of Ca, CA of P. For CA, MA, LA, TA, AA, PA and HCl mineral loss
      was shown to be pH-dependent. Ca dissolution varied between 28.6+/-4.4 (LA, pH 2)
      and 2.4+/-0.7 nmol mm(-2)min(-1) (HCl, pH 3), P dissolution ranged between 17.2+/
      2.6 (LA, pH 2) and 1.4+/-0.4 nmol mm(-2)min(-1) (HCl, pH 3). LA was one of the
      most erosive acids. AA was very erosive at pH 3. HCl and MA were shown to have
      the lowest erosive effects. There was only a weak correlation (r=0.28) between P
      and Ca release and the amount of titratable acid. The method of the present study
      allows investigation of minimal erosive effects via direct determination of P and
      Ca dissolution. During short time exposition at constant pH level, erosive
      effects mainly depend on pH and type of acid but not on amount of titratable
      acid.

PMID- 15848148
TI  - Influence of the time of measurement of unstimulated human whole saliva on the
      diagnosis of hyposalivation.
AB  - OBJECTIVE: An unstimulated whole saliva flow rate (UWSFR) of less than 0.1 mL/min
      is often related to symptoms of dry mouth. It is also used as a diagnostic
      criterion for Sjogren's syndrome, and for assessment of hyposalivation as a
      caries risk factor. The main hypothesis was that the circadian rhythm of salivary
      flow affects this diagnosis if saliva is collected at different morning time
      points. DESIGN: UWSFR was tested at 7:30 and 11:30 a.m. in 108 individuals, age
      15-46 years (mean 33+/-9). The participants were allocated to one of three groups
      (very low< or =0. 1/min, low 0.1-0.2 mL/min and normal>0.2 mL/min) based on the
      UWSFR at 7:30 a.m. Different aspects of the perception of oral dryness were rated
      using Visual Analog Scales. RESULTS: All three groups displayed a statistically
      significant increase in UWSFR at 11:30 a.m. compared with 7:30 a.m., all of
      similar magnitude (0.08-0.09 mL/min). In the group with very low UWSFR, 70% at
      11:30 a.m. exceeded the 0.1 mL/min limit. There were significant difference in
      perception of oral dryness between the normal group and both the low and the very
      low groups. Only the subjects in the groups with a low or very low UWSFR
      perceived an increase in oral wetness at 11:30 a.m. CONCLUSIONS: It was concluded
      that the time of measurement strongly influences the diagnosis of hyposalivation.
      To control the influence of variations in the time of saliva collection, we
      suggest that unstimulated whole saliva tests are performed at a fixed time-point
      or in a limited time interval early in the morning.

PMID- 15848149
TI  - The unstimulated salivary flow rate after prolonged gum chewing.
AB  - OBJECTIVE: To determine whether, after a prolonged period of gum chewing, the
      unstimulated salivary flow rate falls below the unstimulated flow rate before gum
      chewing. DESIGN: Six males and six females each collected whole saliva at
      intervals for up to 105 min on two separate days. On one control day they
      collected unstimulated saliva over the -10 to 0 and 90 to 105 min periods. On the
      other day, they made the same collections of unstimulated saliva but, in
      addition, chewed two tablets of Wrigley's peppermint-flavoured gum over the 0-90
      min period. The data on flow rates were subjected to repeated-measures ANOVA and
      Duncan tests. RESULTS: The unstimulated flow rates in the -10 to 0 and 90 to 105
      min periods were not significantly different on the same day or between days and
      the values were all significantly less (P<0.05) than the stimulated flow rates,
      while gum was being chewed. CONCLUSION: This study provided no evidence that the
      unstimulated salivary flow rate is reduced after prolonged gum chewing. Patients
      who complain of mouth dryness after prolonged gum chewing may have become
      accustomed to the larger volume of saliva present in the mouth during the gum
      chewing.

PMID- 15848150
TI  - Age-related changes in human sublingual glands: a post mortem study.
AB  - OBJECTIVES: To analyse age- and gender-related microscopic changes in sublingual
      glands obtained from human cadavers. STUDY DESIGN: One hundred eighty six human
      sublingual glands were obtained from 93 autopsies. Approximately five individuals
      of each gender per decade of life were allocated to three age groups: group I (0
      30 years, n=26); group II (31-60 years, n=32) and group III (61-90 years, n=35).
      The specimens were fixed in 10% formalin and submitted to routine histological
      processing, and sections were stained with hematoxylin and eosin. RESULTS:
      Significant differences with increasing age were observed for the following
      microscopic aspects: acinar atrophy (r=0.26, p=0.0115); replacement of parenchyma
      by fibrous tissue (r=0.79, p<0.0001) and/or adipose tissue (r=0.63, p<0.0001);
      oncocytosis (r=0.61, p<0.0001); duct-like structures (chi(2)=14.68, p=0.0006) and
      congested blood vessels (chi(2)=7.18, p=0.0276). The mononuclear infiltrate
      changed from focal to diffuse with age (H=8.47, p=0.0144). No significant
      differences were observed between genders. CONCLUSIONS: The aging process starts
      with acinar atrophy, followed by the presence of duct-like structures and ends
      with the replacement of the parenchyma by fibrous and/or adipose tissue. The
      mononuclear infiltrate changes from focal to diffuse. No difference in the aging
      of the sublingual glands is observed between men and women.

PMID- 15848151
TI  - Quantitative real-time PCR detection of oral Enterococcus faecalis in humans.
AB  - OBJECTIVE: Enterococcus faecalis is consistently associated with recurrent root
      canal infections. Only low concentrations of E. faecalis in the human mouth have
      been demonstrated by culture techniques. Quantitative detection strategies more
      sensitive than culturing, such as quantitative PCR (qPCR), could provide more
      illuminating data. DESIGN: Thirty outpatients attending the University of
      Michigan Graduate Endodontic Clinic for endodontic treatment provided oral rinse
      samples that were analysed for E. faecalis using qPCR and microbiological
      culturing. A SYBR Green I qPCR protocol was developed for the quantifiable
      detection of E. faecalis and total bacteria in oral rinse samples using primers
      designed to target the 16S rRNA gene. Annealing temperature and primer, magnesium
      ion, and dimethyl sulfoxide concentrations were investigated for optimisation of
      the protocol; a minimum sensitivity limit of 23 rRNA copies (an estimated six E.
      faecalis cells) was established for E. faecalis in pure culture, and 104 rRNA
      copies (an estimated 26 E. faecalis cells) in mixed culture. RESULTS: In qPCR
      assays, based on extrapolation from estimated rRNA gene copy numbers, E. faecalis
      comprised 0.0006-0.0047% of a total bacteria load that ranged from 5.92 x 10(5)
      to 5.69 x 10(7) cells/ml of oral rinse. E. faecalis was detected in five (17%)
      samples in concentrations from 114 to 490 cells/ml. In parallel culture assays E.
      faecalis were detected in only two samples (7%) of the five identified by qPCR
      and in concentrations 30 and 240 CFU/ml. CONCLUSIONS: qPCR reported a higher
      incidence of E. faecalis in oral rinse samples than culture techniques and
      afforded greater sensitivity.

PMID- 15848152
TI  - Comparison of agonist-induced Ca2+ responses in rat submandibular acini and
      ducts.
AB  - Changes in intracellular Ca(2+) concentration ([Ca(2+)]i) induced by agonists
      were simultaneously monitored in rat submandibular acini and ducts using a Ca(2+)
      imaging system. Substance P (SP) elicited marked increases in [Ca(2+)]i in acini
      but not in ducts. Carbachol (CCh) increased [Ca(2+)]i in both acini and ducts,
      but the maximal level was higher in acini than in ducts. In contrast, epinephrine
      (Epi) also induced an increase in [Ca(2+)]i in acini and ducts, but to a greater
      extent in ducts than in acini. Isoproterenol (ISO) caused a small but significant
      increase in [Ca(2+)]i in ducts but not acini. Reverse transcriptase-polymerase
      chain reaction (RT-PCR) analysis using total RNA extracted from highly purified
      acinar and ductal cells showed that substance P receptor mRNA was present in
      acini at higher levels than in ducts. In contrast, alpha(1a)-adrenoceptor mRNA
      was more strongly expressed in ducts than in acini. The muscarinic receptors
      (M(3) and M(5)) and beta-adrenoceptors (beta(1) and beta(2)) were expressed at
      equivalent levels in both cell types. These results confirm that acini and ducts
      exhibit significant differences in agonist-induced Ca(2+) responses. Furthermore,
      substance P- and epinephrine-induced Ca(2+) responses were consistent with
      receptor mRNA expression in acini and ducts, but carbachol- and isoproterenol
      induced [Ca(2+)]i increases were not.

PMID- 15848153
TI  - Survivin expression is regulated by an epigenetic mechanism for DMBA-induced
      hamster buccal-pouch squamous-cell carcinomas.
AB  - Apoptosis, also known as programmed cell death, is regulated by a number of
      inhibitory or stimulatory factors. In addition to the pro- and anti-apoptotic Bcl
      2 family proteins, there is also a family of inhibitors of apoptosis protein
      (IAP). Survivin, a member of this IAP family, is selectively upregulated in most
      tumours. The objective of the present study was, therefore, to investigate the
      protein and mRNA expression of survivin, as well as the methylation status of the
      CpG sites in exon 1 of the survivin gene for 7,12-dimethylbenz[a]anthracene
      (DMBA)-induced hamster buccal-pouch squamous-cell carcinomas. Immunohistochemical
      analysis for protein expression, RT-PCR for mRNA expression, and a PCR-based
      methylation assay were performed on 26 samples of hamster buccal pouches. The
      total study population was assigned into either one experimental group (15-week
      DMBA treatment; n=13) or two control groups (untreated: n=6; mineral-oil treated
      n=7). Cytoplasmic staining of survivin protein and mRNA were detected in all of
      the hamster buccal-pouch tissue specimens treated with DMBA, whereas neither
      survivin protein nor survivin mRNA were noted for all of the untreated and
      mineral oil-treated hamster buccal-pouch tissue specimens. Furthermore, all the
      untreated and mineral-oil treated samples had a survivin-methylated allele,
      whereas the DMBA-treated cancerous tissues showed no evidence of survivin
      methylation. The results suggest that survivin may play an important role in DMBA
      induced hamster buccal-pouch carcinomas, and that the gene expression may be
      modulated by an epigenetic mechanism.

PMID- 15848154
TI  - Water and molecular chaperones act as weak links of protein folding networks:
      energy landscape and punctuated equilibrium changes point towards a game theory
      of proteins.
AB  - Water molecules and molecular chaperones efficiently help the protein folding
      process. Here we describe their action in the context of the energy and
      topological networks of proteins. In energy terms water and chaperones were
      suggested to decrease the activation energy between various local energy minima
      smoothing the energy landscape, rescuing misfolded proteins from conformational
      traps and stabilizing their native structure. In kinetic terms water and
      chaperones may make the punctuated equilibrium of conformational changes less
      punctuated and help protein relaxation. Finally, water and chaperones may help
      the convergence of multiple energy landscapes during protein-macromolecule
      interactions. We also discuss the possibility of the introduction of protein
      games to narrow the multitude of the energy landscapes when a protein binds to
      another macromolecule. Both water and chaperones provide a diffuse set of rapidly
      fluctuating weak links (low affinity and low probability interactions), which
      allow the generalization of all these statements to a multitude of networks.

PMID- 15848155
TI  - Molecular mimicry may contribute to pathogenesis of ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic inflammatory bowel disease with mucosal
      inflammation and ulceration of the colon. There seems to be no single etiological
      factor responsible for the onset of the disease. Autoimmunity has been emphasized
      in the pathogenesis of UC. Perinuclear anti-neutrophil cytoplasmic antibodies
      (pANCA) are common in UC, and recently two major species of proteins
      immunoreactive to pANCA were detected in bacteria from the anaerobic libraries.
      This implicates colonic bacterial protein as a possible trigger for the disease
      associated immune response. Autoantibodies and T-cell response against human
      tropomyosin isoform 5 (hTM5), an isoform predominantly expressed in colon
      epithelial cells, were demonstrated in patients with UC but not in Crohn's
      colitis. We identified two bacterial protein sequences in NCBI database that have
      regions of significant sequence homology with hTM5. Our hypothesis is that
      molecular mimicry may be responsible for the pathogenesis of UC.

PMID- 15848156
TI  - RNA silencing: a remarkable parallel to protein-based immune systems in
      vertebrates?
AB  - Sequence-specific gene silencing by double-strand RNA has been observed in many
      eukaryotes. Accumulating data suggest that it is the major antiviral defense
      mechanism in plants and invertebrates. The discovery that this cellular mechanism
      is also highly conserved though somewhat impaired in mammals has stimulated
      debate about the evolution of antiviral systems. Here we suggest that the
      existence of the interferon response as an evolutionary intermediate could
      account for both the relative decline of RNA silencing and the development of
      protein-based immune systems in vertebrates. In addition, we emphasize the
      opportunities presented by RNA silencing and the deeper understanding of
      vertebrate antiviral systems that is needed.

PMID- 15848157
TI  - Significant species-dependence of P700 redox potential as verified by
      spectroelectrochemistry: comparison of spinach and Theromosynechococcus
      elongatus.
AB  - The redox potentials of P700, the primary electron donor of photosystem (PS) I,
      of spinach and Thermosynechococcus elongatus were determined by means of
      spectroelectrochemistry with an error range of +/-2-3 mV, to find that the redox
      potential of P700 in T. elongatus is lower by ca. 50 mV as compared with spinach.
      The shift in the P700 redox potential of PS I core particles prepared by harsh
      detergent treatments remained to within 10 mV for both organisms. These results
      show that the 50 mV difference in the P700 redox potential between the two
      organisms is not a detergent-induced artifact but reflects an intrinsic property
      of each PS I.

PMID- 15848158
TI  - Effect of EPS1 gene deletion in Saccharomyces cerevisiae on the secretion of
      foreign proteins which have disulfide bridges.
AB  - Both amyloid-prone cystatin and unstable mutant C94A lysozyme were secreted in
      wild-type and Deltaeps1 Saccharomyces cerevisiae cells. Amyloid-prone cystatin
      secreted at much higher level in Deltaeps1 cells than that in wild-type yeast. In
      parallel, the secretion amount of disulfide bond disrupted mutant C94A lysozyme
      greatly increased in Deltaeps1 cells although that was apparently low in wild
      type yeast cells compared with the secretion amount of wild-type lysozyme. It is
      interesting that neither the unstable mutant C94A lysozyme nor amyloid-prone
      cystatin secreted in Deltaeps1 cells maintained their specific activities. These
      observations lead to the supposition that yeast cells deficient for the protein
      disulfide isomerase-family-member EPS1 locus secrete more of labile disulfide
      containing model proteins.

PMID- 15848159
TI  - Pancreatic islet response to hyperglycemia is dependent on peroxisome
      proliferator-activated receptor alpha (PPARalpha).
AB  - This study tests the hypothesis that islet peroxisome proliferator-activated
      receptor alpha (PPARalpha) influences insulin secretion. Freshly isolated islets
      of normoglycemic PPARalpha-null mice display no major alteration of glucose
      stimulated insulin release. However, after 24 h of culture in high glucose,
      PPARalpha-null islets exhibit elevated basal insulin secretion and fail to
      increase insulin mRNA. 24-h culture with palmitate replicates this phenotype in
      wild-type islets. The data suggest that PPARalpha is needed to ensure appropriate
      insulin secretory response in situation of short-term hyperglycemia, likely by
      maintaining islet lipid homeostasis. As such, islet PPARalpha could contribute to
      delay the progression of type 2 diabetes.

PMID- 15848160
TI  - The chlorophyll-binding protein IsiA is inducible by high light and protects the
      cyanobacterium Synechocystis PCC6803 from photooxidative stress.
AB  - The products of the isiAB operon are a chlorophyll antenna protein (IsiA) and
      flavodoxin (IsiB), which accumulate in cyanobacteria grown under iron starvation
      conditions. Here we show that strong light triggers de-repression of isiAB
      transcription and leads to IsiA and flavodoxin accumulation under iron replete
      conditions. Genetic deletion of isiAB resulted in a photosensitive phenotype,
      with accumulation of reactive oxygen species and cell bleaching in high light,
      while the flavodoxin-deficient isiB null mutant expressing isiA was
      phototolerant. We conclude that IsiA protects cyanobacteria from photooxidative
      stress. IsiA is the first example of a chlorophyll antenna protein outside the
      extended LHC family that is induced transiently by high light and that fulfills a
      photoprotective role.

PMID- 15848161
TI  - The N137 and P140 amino acids in the p51 and the P95 amino acid in the p66
      subunit of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase are
      instrumental to maintain catalytic activity and to design new classes of anti-HIV
      1 drugs.
AB  - Amino acids N137 and P140 in the p51 subunit of HIV-1 reverse transcriptase (RT)
      are part of the beta7-beta8-loop that contributes to the formation of the base of
      the non-nucleoside RT inhibitor (NNRTI)-binding pocket and makes up a substantial
      part of the dimerization interface. Amino acid P95 in p66 also markedly
      contributes to the dimerization binding energy. Nine RT mutants at amino acid 137
      were constructed bearing the mutations Y, K, T, D, A, Q, S, H or E. The prolines
      at amino acid positions 95 and 140 were replaced by alanine in separate enzymes.
      We found that all mutant RT enzymes showed a dramatically decreased RNA-dependent
      DNA polymerase activity. None of the mutant RT enzymes showed marked resistance
      against any of the clinically used NNRTIs but they surprisingly lost significant
      sensitivity for NRTIs such as ddGTP. The denaturation analyses of the mutant RTs
      by urea are suggestive for a relevant role of N137 in the stability of the RT
      heterodimer and support the view that the beta7-beta8 loop in p51 is a hot spot
      for RT dimerization and instrumental for efficient polymerase catalytic activity.
      Consequently, N137 and P140 in p51 and P95 in p66 should be attractive targets in
      the design of new structural classes of RT inhibitors aimed at compromising the
      optimal interaction of the beta7-beta8 loop in p51 at the p66/p51 dimerization
      interface.

PMID- 15848162
TI  - Crystal structure of alpha-hordothionin at 1.9 Angstrom resolution.
AB  - Crystal structure of ubiquitous toxin from barley alpha-hordothionin (alpha-HT)
      has been determined at 1.9A resolution by X-ray crystallography. The primary
      sequence as well as the NMR solution structure of alpha-HT firmly established
      that alpha-HT belongs to a family of membrane active plant toxins-thionins. Since
      alpha-HT crystallized in a space group (P4(1)2(1)2) that is different from the
      space group (I422) of previously determined alpha(1)- and beta-purothionins, and
      visocotoxin A3, therefore, it provided independent information on protein-protein
      interactions that may be relevant to the toxin mechanism. The structure of alpha
      HT not only confirms overall architectural features (crambin fold) but also
      provides an additional confirmation of the role for crucial solute molecules,
      that were postulated to be directly involved in the mechanism of toxicity for
      thionins.

PMID- 15848163
TI  - AtCCS is a functional homolog of the yeast copper chaperone Ccs1/Lys7.
AB  - In plant chloroplasts two superoxide dismutase (SOD) activities occur, FeSOD and
      Cu/ZnSOD, with reciprocal regulation in response to copper availability. This
      system presents a unique model to study the regulation of metal-cofactor delivery
      to an organelle. The Arabidopsis thaliana gene AtCCS encodes a functional homolog
      to yeast Ccs1p/Lys7p, a copper chaperone for SOD. The AtCCS protein was localized
      to chloroplasts where it may supply copper to the stromal Cu/ZnSOD. AtCCS mRNA
      expression levels are upregulated in response to Cu-feeding and senescence. We
      propose that AtCCS expression is regulated to allow the most optimal use of Cu
      for photosynthesis.

PMID- 15848164
TI  - Role of Cys-295 on subunit interactions and allosteric regulation of
      phosphofructokinase-2 from Escherichia coli.
AB  - In a previous work, chemical modification of Cys-238 of Escherichia coli Pfk-2
      raised concerns on the importance of the dimeric state of Pfk-2 for enzyme
      activity, whereas modification of Cys-295 impaired the enzymatic activity and the
      MgATP-induced tetramerization of the enzyme. The results presented here
      demonstrate that the dimeric state of Pfk-2 is critical for the stability and the
      activity of the enzyme. The replacement of Cys-238 by either Ala or Phe shows no
      effect on the kinetic parameters, allosteric inhibition, dimer stability and
      oligomeric structure of Pfk-2. However, the mutation of Cys-295 by either Ala or
      Phe provokes a decrease in the k(cat) value and an increment in the K(m) values
      for both substrates. We suggest that the Cys-295 residue participates in
      intersubunit interactions in the tetramer since the Cys-295-Phe mutant exhibits
      higher tetramer stability, which in turn results in an increase in the fructose-6
      P concentration required for the reversal of the MgATP inhibition relative to the
      wild type enzyme.

PMID- 15848165
TI  - Gene expression and characterization of two 2-oxoacid:ferredoxin oxidoreductases
      from Aeropyrum pernix K1.
AB  - A hyperthermophilic and aerobic crenarchaeon, Aeropyrum pernix K1, has two sets
      of genes possibly encoding 2-oxoacid:ferredoxin oxidoreductases. One is encoded
      in open reading frames (ORFs) ape2126 and ape2128, and the other in ORFs ape1473
      and ape1472. The two sets of genes were expressed. The product enzymes,
      Ape2126/2128 and Ape1473/1472, showed optimal temperatures of 105 and over 110
      degrees C, and optimal pHs of 8.5 and 9.0, respectively, using pyruvate as a
      substrate. Pyruvate, 2-oxobutyrate, and glyoxylate were the best substrates for
      both enzymes, and additionally Ape1473/1472 was able to act on 2-oxoglutarate,
      suggesting the enzyme operates in the TCA cycle.

PMID- 15848166
TI  - RB18A enhances expression of mutant p53 protein in human cells.
AB  - RB18A (TRAP220/DRIP205) is a cofactor of transcription. We herein demonstrated
      that RB18A downregulated p53 and upregulated MDM2 promoters. These RB18A
      regulations, not modified by p53wt expression, were inhibited by mutant p53
      (p53mut) expression, which directly interacts with RB18A D5 domain. In addition,
      RB18A via its D4 domain, also interacts directly and specifically with MDM2
      protein inhibiting p53mut degradation. Altogether, these mechanisms contribute to
      maintain a high level of p53mut expression in tumor proliferating cells.
      Therefore, RB18A plays a central role to control p53wt and p53mut protein content
      and functions in cells through a loop of regulation, which involves MDM2.

PMID- 15848167
TI  - Human mitochondrial peroxiredoxin 5 protects from mitochondrial DNA damages
      induced by hydrogen peroxide.
AB  - Peroxiredoxin 5 is a thioredoxin peroxidase ubiquitously expressed in mammalian
      tissues. Peroxiredoxin 5 can be addressed intracellularly to mitochondria,
      peroxisomes, the cytosol and the nucleus. Here, we show that mitochondrial human
      peroxiredoxin 5 protects mitochondrial DNA (mtDNA) from oxidative attacks. In an
      acellular assay, recombinant peroxiredoxin 5 was shown to protect plasmid DNA
      from damages induced by metal-catalyzed generation of reactive oxygen species. In
      Chinese hamster ovary cells, overexpression of mitochondrial peroxiredoxin 5
      significantly decreased mtDNA damages caused by exogenously added hydrogen
      peroxide. Altogether our results suggest that mitochondrial peroxiredoxin 5 may
      play an important role in mitochondrial genome stability.

PMID- 15848168
TI  - Heparanase processing by lysosomal/endosomal protein preparation.
AB  - Heparanase is an endo-beta-glucuronodase involved in cleavage of heparan sulfate
      side chains, activity that is strongly implicated in cell dissemination
      associated with tumor metastasis and inflammation. Heparanase is first
      synthesized as a latent 65 kDa precursor that is converted into an active enzyme
      upon proteolytic processing. Previously, we have reported that elevation of the
      lysosomal pH results in complete inhibition of heparanase processing, suggesting
      that lysosomal protease(s) and acidic pH conditions are required for heparanase
      processing. Here, we adopted a cell fractionation approach and provide evidence
      that incubation of the pro-enzyme with lysosome/endosome, but not with
      cytoplasmic fractions resulted in processing and activation of the 65 kDa latent
      heparanase. Moreover, while the water soluble lysosome/endosome fraction
      exhibited no apparent processing activity, heparanase processing by the water
      insoluble lysosome/endosome membrane fraction was readily detected and exhibited
      the expected pH dependency.

PMID- 15848169
TI  - Fyn binding protein, Fyb, interacts with mammalian actin binding protein, mAbp1.
AB  - The immune cell specific protein Fyn-T binding protein (Fyb) has been identified
      as a target of the Yersinia antiphagocytic effector Yersinia outer protein H
      (YopH), but its role in macrophages is unknown. By using Fyb domains as bait to
      screen a mouse lymphoma cDNA library, we identified a novel interaction partner,
      mammalian actin binding protein 1 (mAbp1). We show that mAbp1 binds the Fyb N
      terminal via its C-terminally located src homology 3 domain. The interaction
      between Fyb and mAbp1 is detected in macrophage lysates and the proteins co
      localize with F-actin in the leading edge. Hence, mAbp1 is likely to constitute a
      downstream effector of Fyb involved in F-actin dynamics.

PMID- 15848170
TI  - Unrip is a component of SMN complexes active in snRNP assembly.
AB  - A macromolecular complex containing survival of motor neurons (SMN), the spinal
      muscular atrophy protein, and Gemin2-7 interacts with Sm proteins and snRNAs to
      carry out the assembly of these components into spliceosomal small nuclear
      ribonucleoproteins (snRNPs). Here we report the characterization of unr
      interacting protein (unrip), a GH-WD protein of unknown function, as a component
      of the SMN complex that interacts directly with Gemin6 and Gemin7. Unrip also
      binds a subset of Sm proteins, and unrip-containing SMN complexes are necessary
      and sufficient to mediate the assembly of spliceosomal snRNPs. These results
      demonstrate that unrip functions in the pathway of snRNP biogenesis and is a
      marker of cellular SMN complexes active in snRNP assembly.

PMID- 15848171
TI  - The cell surface receptor G6b, a member of the immunoglobulin superfamily, binds
      heparin.
AB  - The G6b gene, located in the human Major Histocompatibility Complex, encodes a
      receptor of the immunoglobulin (Ig) superfamily. In this study, we show using a
      variety of techniques that the extracellular domain of the G6b protein,
      containing a single Ig-like domain, binds to heparin with high affinity. In an
      ELISA assay, this binding was displaceable with soluble heparin with an IC50
      value of approximately 0.5 microg/ml. Other sulfated glycans showed weaker or no
      competition. The observed interaction between G6b and heparin is strongly salt
      dependent suggesting a mainly electrostatic interaction. Heparin might modulate
      the interaction of G6b with its as yet unidentified protein ligand.

PMID- 15848172
TI  - Aberrant glycosylation of alpha-dystroglycan causes defective binding of laminin
      in the muscle of chicken muscular dystrophy.
AB  - Dystroglycan is a central component of dystrophin-glycoprotein complex that links
      extracellular matrix and cytoskeleton in skeletal muscle. Although dystrophic
      chicken is well established as an animal model of human muscular dystrophy, the
      pathomechanism leading to muscular degeneration remains unknown. We show here
      that glycosylation and laminin-binding activity of alpha-dystroglycan (alpha-DG)
      are defective in dystrophic chicken. Extensive glycan structural analysis reveals
      that Galbeta1-3GalNAc and GalNAc residues are increased while Siaalpha2-3Gal
      structure is reduced in alpha-DG of dystrophic chicken. These results implicate
      aberrant glycosylation of alpha-DG in the pathogenesis of muscular degeneration
      in this model animal of muscular dystrophy.

PMID- 15848173
TI  - Caspase-3 can be pseudo-activated by a Ca2+-dependent proteolysis at a non
      canonical site.
AB  - We have shown previously that calcium could trigger nuclear fragmentation, which
      was associated with a caspase 3 (C3)-like activity [Juin, P., Pelletier, M.,
      Oliver, L., Tremblais, K., Gregoire, M., Meflah, K. and Vallette, F.M. (1998)
      Induction of a caspase-3-like activity by calcium in normal cytosolic extracts
      triggers nuclear apoptosis in a cell-free system. J. Biol. Chem. 273, 17559].
      Here, we report that this activation is associated with a non-canonical
      truncation of C3, which induces a weak DEVDase activity. The cleavage of C3 via
      calcium-dependent proteolysis is independent of caspase 9; lysate exposure to
      calcium prevents further cleavage and activation by the cytochrome c and dATP
      pathway. Altogether, our data suggest that calcium could favour a necrotic
      mechanism by inducing the generation of a form of C3 insensitive to mitochondrial
      activation.

PMID- 15848174
TI  - Involvement of matrix metalloproteinase-9 in platelet-activating factor-induced
      angiogenesis.
AB  - Platelet-activating factor (PAF) augments angiogenesis by promoting the synthesis
      of various angiogenic factors, via the activation of NF-kappaB. In this study, we
      investigated the role of the matrix metalloproteinase (MMP)-9, in PAF-induced
      angiogenesis. PAF increased mRNA expression, protein synthesis, and MMP-9
      activity in ECV304 cells, in a NF-kappaB-dependent manner. PAF increased MMP-9
      promoter activity in ECV304, which was inhibited by WEB2107, and NF-kappaB
      inhibitors. Transfected NF-kappaB subunits, p65 or/and p50, increased luciferase
      activity in the reporter plasmid MMP-9, resulting in an increase not only of MMP
      9 luciferase activity, but also of mRNA expression in MMP-9. MMP-9 or NF-kappaB
      inhibitors significantly inhibited PAF-induced angiogenesis, in a dose-dependent
      manner, in an in vivo mouse Matrigel implantation model. In a parallel to the
      Matrigel implantation study, MMP-9 or NF-kappaB inhibitors inhibited PAF-induced
      sprouting of porcine pulmonary arterial endothelial cells. These data indicate
      that NF-kappaB-dependent MMP-9 plays a key role in PAF-induced angiogenesis.

PMID- 15848175
TI  - PTEN expression in ovine granulosa cells increases during terminal follicular
      growth.
AB  - In the present paper, we have studied the expression of the Phosphatase and
      TENsin homolog deleted on chromosome 10 (PTEN) and its putative biological role
      in the sheep ovary. We found by Northern-blot, immunohistochemistry and
      immunoblot that PTEN is highly expressed in granulosa cells from large
      differentiated follicles (LF) in comparison with small proliferating follicles
      (SF) (P < 0.001), with no clear effect of follicle quality. Moreover, the PTEN
      lipid phosphatase activity is also higher in LF than in SF (P < 0.01). In
      contrast, levels of the phosphorylated form of AKT (pAKT) are lower in LF than in
      SF (P < 0.0001). IGF-I and insulin but not FSH, LH or forskolin are able to
      stimulate the expression of PTEN mRNA (P < 0.001) and protein by ovine granulosa
      cells after 48 h of culture in vitro. An IGF-1 time course analysis showed that
      expression of PTEN protein appeared after 12h of culture, concomitant with the
      fall of the pAKT levels, which peaked after 6h of stimulation with IGF-I.
      Moreover, transfection experiments showed that overexpression of PTEN in ovine
      granulosa cells induced a decrease and an increase in E2F and p27 promoter
      activity, respectively (P < 0.05). Overall, our present data show for the first
      time that the expression of PTEN increases during terminal follicular growth.
      This increase, that might be induced by IGF-I but not FSH, would participate in
      the proliferation/differentiation transition of ovine granulosa cells in
      differentiating follicles.

PMID- 15848176
TI  - Mutations in the "lid" region affect chain length specificity and thermostability
      of a Pseudomonas fragi lipase.
AB  - The cold-adapted Pseudomonas fragi lipase (PFL) displays highest activity on
      short-chain triglyceride substrates and is rapidly inactivated at moderate
      temperature. Sequence and structure comparison with homologous lipases endowed
      with different substrate specificity and stability, pointed to three polar
      residues in the lid region, that were replaced with the amino acids conserved at
      equivalent positions in the reference lipases. Substitutions at residues T137 and
      T138 modified the lipase chain-length preference profile, increasing the relative
      activity towards C8 substrates. Moreover, mutations conferred to PFL higher
      temperature stability. On the other hand, replacement of the serine at position
      141 by glycine destabilized the protein.

PMID- 15848177
TI  - Sumoylation of the nucleocapsid protein of severe acute respiratory syndrome
      coronavirus.
AB  - Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes a highly basic
      nucleocapsid (N) protein of 422 amino acids. Similar to other coronavirus N
      proteins, SARS-CoV N protein is predicted to be phosphorylated and may contain
      nuclear localization signals, serine/arginine-rich motif, RNA binding domain and
      regions responsible for self-association and homo-oligomerization. In this study,
      we demonstrate that the protein is posttranslationally modified by covalent
      attachment to the small ubiquitin-like modifier. The major sumoylation site was
      mapped to the (62)lysine residue of the N protein. Further expression and
      characterization of wild type N protein and K62A mutant reveal that sumoylation
      of the N protein drastically promotes its homo-oligomerization, and plays certain
      roles in the N protein-mediated interference of host cell division. This is the
      first report showing that a coronavirus N protein undergoes posttranslational
      modification by sumoylation, and the functional implication of this modification
      in the formation of coronavirus ribouncleoprotein complex, virion assembly and
      virus-host interactions.

PMID- 15848178
TI  - The characterization of plasma membrane Ca2+-ATPase in rich sphingomyelin
      cholesterol domains.
AB  - According to the raft hypothesis, sphingolipid-cholesterol (CHOL) microdomains
      are involved in numerous cellular functions. Here, we have prepared liposomes to
      simulate the lipid composition of rafts/caveolae using phosphatidylchone,
      sphingomyelin (SPM)-CHOL in vitro. Experiments of both 1,6-diphenyl-1,3,5
      hexatriene and merocyanine-540 fluorescence showed that a phase transition from
      l(d) to l(o) can be observed clearly. In particular, we investigated the behavior
      of a membrane protein, plasma membrane Ca(2+)-ATPase (PMCA), in lipid rafts (l(o)
      phase). Three complementary approaches to characterize the physical appearance of
      PMCA were employed in the present study. Tryptophan intrinsic fluorescence
      increase, fluorescence quenching by both acrylamid and hypocrellin B decrease,
      and MIANS fluorescence decrease, indicate that the conformation of PMCA embedded
      in lipid l(o) phase is more compact than in lipid l(d) phase. Also, our results
      showed that PMCA activity decreased with the increase of SPM-CHOL content, in
      other words, with the increase of l(o) phase. This suggests that the specific
      domains containing high SPM-CHOL concentration are not a favorable place for PMCA
      activity. Finally, a possible explanation about PMCA molecules concentrated in
      caveolae/rafts was discussed.

PMID- 15848179
TI  - Small interfering RNA inhibits SARS-CoV nucleocapsid gene expression in cultured
      cells and mouse muscles.
AB  - SARS-CoV is a newly identified coronavirus that causes severe acute respiratory
      syndrome (SARS). Currently, there is no effective method available for
      prophylaxis and treatment of SARS-CoV infections. In the present study, the
      influence of small interfering RNA (siRNA) on SARS-CoV nucleocapsid (N) protein
      expression was detected in cultured cells and mouse muscles. Four siRNA
      expression cassettes driven by mouse U6 promoter targeting SARS-CoV N gene were
      prepared, and their inhibitory effects on expression of N and enhanced green
      fluorescence protein (EGFP) fusion protein were observed. A candidate siRNA was
      proved to down-regulate N and EGFP expression actively in a sequence-specific
      manner. The expression vector of this siRNA was constructed and confirmed to
      reduce N and EGFP expression efficiently in both cultured cells and adult mouse
      muscles. Our findings suggest that the siRNA should provide the basis for
      prophylaxis and therapy of SARS-CoV infection in human.

PMID- 15848180
TI  - Apoptosis repressor with caspase recruitment domain (ARC) is expressed in cancer
      cells and localizes to nuclei.
AB  - Apoptosis repressor with caspase recruitment domain is expressed at high levels
      in brain and myogenic tissues, consistent with a role to inhibit apoptosis in the
      terminally differentiated cells. Expression of ARC in cancers is not known. In
      this study, we reported that ARC was highly expressed in various non-myogenic and
      non-neurogenic human and rat cancer cell lines. Unexpectedly, ARC was localized
      almost exclusively to the nuclei of cancer cells, which was unlike the
      cytoplasmic localization of ARC in non-cancer cells. Furthermore, nuclear ARC in
      cancer cells did not co-localize with nucleolus protein of 30 kDa, an
      alternatively spliced ARC isoform. These findings indicate that ARC is
      distributed differently in cancer cells than non-cancer cells and thus might play
      a role in neoplastic transformation.

PMID- 15848181
TI  - Perchloric acid-soluble protein regulates cell proliferation and differentiation
      in the spinal cord of chick embryos.
AB  - The role of perchloric acid-soluble protein (PSP) was investigated in chick
      embryos. Fluorescently labeled anti-chick liver (CL)-PSP IgG was injected into
      the yolk sac in ovo at embryonic day 3, and became localized in neuroepithelial
      cells. Within 12 h, morphological changes were observed in 37.5% of anti-CL-PSP
      IgG-injected embryos, and the neuroepithelial cells formed a wavy line. No
      significant changes were observed in embryos injected with non-immune IgG or PBS.
      Increased expression of PCNA and decreased expression of neuronal class III beta
      tubulin were observed in the spinal cord after anti-CL-PSP IgG injection. These
      results suggest that PSP controls the proliferation and differentiation of
      neuroepithelial cells in chick embryos.

PMID- 15848182
TI  - Nitration and oligomerization of tau induced by peroxynitrite inhibit its
      microtubule-binding activity.
AB  - Abnormally nitrated tau has been found recently in the neurofibrillary tangles of
      Alzheimer's disease (AD). However, whether and how nitration of tau is involved
      in AD pathology is not known. Herein, we found that in vitro incubation of
      peroxynitrite with recombinant tau resulted in nitration and oligomerization of
      tau in a dosage-dependent manner. Moreover, the nitrated tau showed a
      significantly decreased binding activity to taxol-stabilized microtubulesin in
      vitro. Further study demonstrated that peroxynitrite also induced tau nitration
      in neuroblastoma N2a cell line, and the nitrated tau was accumulated in the
      cells. We conclude that abnormal nitration of tau contributes to the impaired
      biological activity of tau in binding to the microtubules and the aggregation of
      tau, implying a novel mechanism responsible for the neurodegeneration seen in AD
      brain.

PMID- 15848183
TI  - The subcellular compartmentation of fatty acid transporters is regulated
      differently by insulin and by AICAR.
AB  - Cellular fatty acid uptake is facilitated by a number of fatty acid transporters,
      FAT/CD36, FABPpm and FATP1. It had been presumed that FABPpm, was confined to the
      plasma membrane and was not regulated. Here, we demonstrate for the first time
      that FABPpm and FATP1 are also present in intracellular depots in cardiac
      myocytes. While we confirmed previous work that insulin and AICAR each induced
      the translocation of FAT/CD36 from an intracellular depot to the PM, only AICAR,
      but not insulin, induced the translocation of FABPpm. Moreover, neither insulin
      nor AICAR induced the translocation of FATP1. Importantly, the increased
      plasmalemmal content of these LCFA transporters was associated with a concomitant
      increase in the initial rate of palmitate uptake into cardiac myocytes.
      Specifically, the insulin-stimulated increase in the rate of palmitate uptake
      (+60%) paralleled the insulin-stimulated increase in plasmalemmal FAT/CD36
      (+34%). Similarly, the greater AICAR-stimulated increase in the rate of palmitate
      uptake (+90%) paralleled the AICAR-induced increase in both plasmalemmal proteins
      (FAT/CD36 (+40%)+FABPpm (+36%)). Inhibition of palmitate uptake with the specific
      FAT/CD36 inhibitor SSO indicated that FABPpm interacts with FAT/CD36 at the
      plasma membrane to facilitate the uptake of palmitate. In conclusion, (1) there
      appears to be tissue-specific sensitivity to insulin-induced FATP1 translocation,
      as it has been shown elsewhere that insulin induces FATP1 translocation in 3T3-L1
      adipocytes, and (2) clearly, the subcellular distribution of FABPpm, as well as
      FAT/CD36, is acutely regulated in cardiac myocytes, although FABPpm and FAT/CD36
      do not necessarily respond identically to the same stimuli.

PMID- 15848184
TI  - The yeast eIF4E-associated protein Eap1p attenuates GCN4 translation upon TOR
      inactivation.
AB  - Amino acid-starved yeast activates the eIF2alpha kinase Gcn2p to suppress general
      translation and to selectively derepress the transcription factor Gcn4p, which
      induces various biosynthetic genes to elicit general amino acid control (GAAC).
      Well-fed yeast activates the target of rapamycin (TOR) to stimulate translation
      via the eIF4F complex. A crosstalk was demonstrated between the pathways for GAAC
      and TOR signaling: the TOR-specific inhibitor rapamycin activates Gcn2p. Here we
      demonstrate that, upon TOR-inactivation, the putative TOR-regulated eIF4E
      associated protein Eap1p likely functions downstream of Gcn2p to attenuate GCN4
      translation via a mechanism independent of eIF4E-binding, thereby constituting
      another interface between the two pathways.

PMID- 15848185
TI  - Reversible PEGylation of peptide YY3-36 prolongs its inhibition of food intake in
      mice.
AB  - Administration of peptide YY(3-36) (PYY(3-36)) to fasting humans or mice shortly
      before re-feeding effectively reduced their food intake, but PYY(3-36) exhibited
      a functional half-life of only approximately 3 h. Attachment of poly(ethylene
      glycol) to proteins and peptides (PEGylation) prolongs their half-life in vivo,
      but completely inactivated PYY(3-36). We developed a reversibly PEGylated PYY(3
      36) derivative by coupling it to a 40 kDa PEG through a spontaneously cleavable
      linker. The resulting conjugate (PEG(40)-FMS-PYY(3-36)) gradually released
      unmodified PYY(3-36) in vivo, exhibiting an eightfold increase in its functional
      half-life, to approximately 24h. This long-acting PYY(3-36) pro-drug may serve as
      an effective means for controlling food intake in humans.

PMID- 15848186
TI  - The hydrophobic surface of PaAMP from pokeweed seeds is essential to its
      interaction with fungal membrane lipids and the antifungal activity.
AB  - PaAMP is a small seed-specific antimicrobial protein from pokeweeds. It has a
      cysteine-knot fold with a positive patch and a hydrophobic surface. Site-specific
      mutagenesis was performed to study the roles of these two domains in
      antimicrobial activity and we found that the mutations in the hydrophobic surface
      had a more profound effect than that in the positive patch. A protein-membrane
      interaction was observed with the green fluorescence protein-PaAMP (GFP-AMP)
      fusion protein. The mutations that replace the amino acid residues forming
      hydrophobic surface with neutral residues abolished the interaction of PaAMP with
      the membrane and the binding of PaAMP to fungal sphingolipids while ergosterol
      enhanced the binding, suggesting that the hydrophobic surface was required for
      the interaction between PaAMP and fungal plasma membrane lipid raft.

PMID- 15848187
TI  - Origin, distribution and 3D-modeling of Gr-EXPB1, an expansin from the potato
      cyst nematode Globodera rostochiensis.
AB  - Southern analysis showed that Gr-EXPB1, a functional expansin from the potato
      cyst nematode Globodera rostochiensis, is member of a multigene family, and EST
      data suggest expansins to be present in other plant parasitic nematodes as well.
      Homology modeling predicted that Gr-EXPB1 domain 1 (D1) has a flat beta-barrel
      structure with surface-exposed aromatic rings, whereas the 3D structure of Gr
      EXPB1-D2 was remarkably similar to plant expansins. Gr-EXPB1 shows highest
      sequence similarity to two extracellular proteins from saprophytic soil
      inhabiting Actinobacteria, and includes a bacterial type II carbohydrate-binding
      module. These results support the hypothesis that a number of pathogenicity
      factors of cyst nematodes is of procaryotic origin and were acquired by
      horizontal gene transfer.

PMID- 15848188
TI  - Structure of ACC synthase inactivated by the mechanism-based inhibitor L
      vinylglycine.
AB  - L-Vinylglycine (L-VG) is both a substrate for and a mechanism-based inhibitor of
      1-aminocyclopropane-1-carboxylate (ACC) synthase. The ratio of the rate constants
      for catalytic conversion to alpha-ketobutyrate and ammonia to inactivation is
      500/1. The crystal structure of the covalent adduct of the inactivated enzyme was
      determined at 2.25 Angstroms resolution. The active site contains an external
      aldimine of the adduct of L-VG with the pyridoxal 5'-phosphate cofactor. The side
      chain gamma-carbon of L-VG is covalently bound to the epsilon-amino group of
      Lys273. This species corresponds to one of the two alternatives proposed by Feng
      and Kirsch [Feng, L. and Kirsch, J.F. (2000) L-Vinylglycine is an alternative
      substrate as well as a mechanism-based inhibitor of 1-aminocyclopropane-1
      carboxylate synthase. Biochemistry 39, 2436-2444] and presumably results from
      Michael addition to a vinylglycine ketimine intermediate.

PMID- 15848189
TI  - Phoslactomycin targets cysteine-269 of the protein phosphatase 2A catalytic
      subunit in cells.
AB  - According to the chemical genetic approach, small molecules that bind directly to
      proteins are used to analyze protein function, thereby enabling the elucidation
      of complex mechanisms in mammal cells. Thus, it is very important to identify the
      molecular targets of compounds that induce a unique phenotype in a target cell.
      Phoslactomycin A (PLMA) is known to be a potent inhibitor of protein Ser/Thr
      phosphatase 2A (PP2A); however, the inhibitory mechanism of PP2A by PLMA has not
      yet been elucidated. Here, we demonstrated that PLMA directly binds to the PP2A
      catalytic subunit (PP2Ac) in cells by using biotinylated PLMA, and the PLMA
      binding site was identified as the Cys-269 residue of PP2Ac. Moreover, we
      revealed that the Cys-269 contributes to the potent inhibition of PP2Ac activity
      by PLMA. These results suggest that PLMA is a PP2A-selective inhibitor and is
      therefore expected to be useful for future investigation of PP2A function in
      cells.

PMID- 15848190
TI  - ATP potentiates the formation of AChR aggregate in the co-culture of NG108-15
      cells with C2C12 myotubes.
AB  - The role of adenosine 5'-triphosphate (ATP) and P2Y(1) nucleotide receptor in
      potentiating agrin-induced acetylcholine receptor (AChR) aggregation is being
      demonstrated in a co-culture system of NG108-15 cell, a mouse neuroblastoma X rat
      glioma hybrid cell line that resembles spinal motor neuron, with C2C12 myotube.
      In the co-cultures, antagonized P2Y(1) receptors showed a reduction in NG108-15
      cell-induced AChR aggregation. Parallel to this observation, cultured NG108-15
      cell secreted ATP into the conditioned medium in a time-dependent manner.
      Enhancement of ATP release from the cultured NG108-15 cells by overexpression of
      active mutants of small GTPases increased the aggregation of AChRs in co
      culturing with C2C12 myotubes. In addition, ecto-nucleotidase was revealed in the
      co-culture, which rapidly degraded the applied ATP. These results support the
      notion that ATP has a role in directing the formation of post-synaptic apparatus
      in vertebrate neuromuscular junctions.

PMID- 15848191
TI  - Histamine elevates the expression of Ets-1, a protooncogen in human melanoma cell
      lines through H2 receptor.
AB  - Histamine is known to act, at least in part, as a growth factor for several cell
      types, and as production of this biogen amine has been found to accelerate the
      rate of tissue proliferation in wound repair, embryogenesis and malignant growth.
      Abundant experimental and clinical data suggest that histamine augments in vivo
      tumour cell proliferation via histamine H2 receptors (H2R). Here, we report that
      exogenously added histamine stimulates Ets-1 (v-ets erythroblastosis virus E26
      oncogene homolog 1) synthesis in human melanoma cells. Involvement of histamine
      receptors in the histamine induced ets-1 expression has been also studied. Our
      data show that these newly recognized actions of histamine are mediated by the
      H2R. Modification of local protooncogen Ets-1 level is likely being involved in
      the regulation of melanoma growth.

PMID- 15848192
TI  - Modified nicotine metabolism in transgenic tobacco plants expressing the human
      cytochrome P450 2A6 cDNA.
AB  - In this study, the human cytochrome P450 (CYP) 2A6 was used in order to modify
      the alkaloid production of tobacco plants. The cDNA for human CYP2A6 was placed
      under the control of the constitutive 35S promoter and transferred into Nicotiana
      tabacum via Agrobacterium-mediated transformation. Transgenic plants showed
      formation of the recombinant CYP2A6 enzyme but no obvious phenotypic changes.
      Unlike wild-type tobacco, the transgenic plants accumulated cotinine, a
      metabolite which is usually formed from nicotine in humans. This result
      substantiates that metabolic engineering of the plant secondary metabolism via
      mammalian P450 enzymes is possible in vivo.

PMID- 15848193
TI  - Mass spectrometric identification of a novel phosphorylation site in subunit
      NDUFA10 of bovine mitochondrial complex I.
AB  - Mitochondrial Complex I (NADH:ubiquinone oxidoreductase) consists of at least 46
      subunits. Phosphorylation of the 42-kDa subunit NDUFA10 was recently reported
      using a novel phosphoprotein stain [Schulenberg et al. (2003) Analysis of steady
      state protein phosphorylation in mitochondria using a novel fluorescent
      phosphosensor dye. J. Biol. Chem. 278, 27251]. Two smaller Complex I
      phosphoproteins, ESSS and MWFE, and their sites of modification, have since been
      determined [Chen et al. (2004) The phosphorylation of subunits of complex I from
      bovine heart mitochondria. J. Biol. Chem. 279, 26036]. Here we identify the site
      of phosphorylation in NDUFA10 from bovine heart mitochondria by tandem mass
      spectrometry. A single phosphopeptide spanning residues 47-60 was identified and
      confirmed by synthesis to be (47)LITVDGNICSGKpSK(60), establishing serine-59 as
      the site of phosphorylation.

PMID- 15848194
TI  - A recombinant diheme SoxAX cytochrome - implications for the relationship between
      EPR signals and modified heme-ligands.
AB  - The multiheme SoxAX proteins are notable for their unusual heme ligation (His/Cys
      persulfide in the SoxA subunit) and the complexity of their EPR spectra. The
      diheme SoxAX protein from Starkeya novella has been expressed using Rhodobacter
      capsulatus as a host expression system. rSoxAX was correctly formed in the
      periplasm of the host and contained heme c in similar amounts as the native
      SoxAX. ESI-MS showed that the full length rSoxA, in spite of never having
      undergone catalytic turnover, existed in several forms, with the two major forms
      having masses of 28687 +/- 4 and 28718 +/- 4 Da. The latter form exceeds the
      expected mass of rSoxA by 31 +/- 4 Da, a mass close to that of a sulfur atom and
      indicating that a fraction of the recombinant protein contains a cysteine
      persulfide modification. EPR spectra of rSoxAX contained all four heme-dependent
      EPR signals (LS1a, LS1b, LS2, LS3) found in the native SoxAX proteins isolated
      from bacteria grown under sulfur chemolithotrophic conditions. Exposure of the
      recombinant SoxAX to different sulfur compounds lead to changes in the SoxA mass
      profile as determined by ESI while maintaining a fully oxidized SoxAX visible
      spectrum. Thiosulfate, the proposed SoxAX substrate, did not cause any mass
      changes while after exposure to dimethylsulfoxide a +112 +/- 4 Da form of SoxA
      became dominant in the mass spectrum.

PMID- 15848195
TI  - Functional regulation of Na+-dependent neutral amino acid transporter ASCT2 by S
      nitrosothiols and nitric oxide in Caco-2 cells.
AB  - We describe the regulation mechanisms of the Na(+)-dependent neutral amino acid
      transporter ASCT2 via nitric oxide (NO) in the human intestinal cell line, Caco
      2. Exposure of Caco-2 cells to S-nitrosothiol, such as S-nitroso-N-acetyl-DL
      penicillamine (SNAP) and S-nitrosoglutathione, and the NO-donor, NOC12,
      concentration- and time-dependently increased Na(+)-dependent alanine uptake.
      Kinetic analyses indicated that SNAP increases the maximal velocity (V(max)) of
      Na(+)-dependent alanine uptake in Caco-2 cells without affecting the Michaelis
      Menten constant (K(t)). The stimulatory effect was partially eliminated by
      actinomycin D and cycloheximide. Increased Na(+)-dependent alanine uptake by SNAP
      was partially abolished by the NO scavengers, 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl 3-oxide sodium salt (carboxy-PTIO) and N
      (dithiocarboxy)sarcosine disodium salts (DTCS), as well as the NADPH oxidase
      inhibitor, diphenyleneiodonium. RT-PCR revealed that Caco-2 cells expressed the
      Na(+)-dependent neutral amino acid transporter ASCT2, but not the other Na(+)
      dependent neutral amino acid transporters ATB(0,+) and B(0)AT1. These results
      suggested that functional up-regulation of ASCT2 by SNAP might be partially
      associated with an increase in the density of transporter protein via de novo
      synthesis.

PMID- 15848196
TI  - The FAXWXXT motif in the carboxyl terminus of Vibrio mimicus metalloprotease is
      involved in binding to collagen.
AB  - We have shown previously that the C-terminal region of the extracellular
      metalloprotease of Vibrio mimicus (VMC) is essential for collagenase activity.
      Here, we demonstrate that deletion of 100 amino acids, but not 67 amino acids,
      from the C-terminus of the intact VMC protein (VMC61) abolished the collagenase
      activity. The intervening 33-amino acid region contains a repeated FAXWXXT motif
      that is essential for insoluble type I collagen binding; the isolated 33-amino
      acid peptide bound to insoluble type I collagen, while a peptide containing only
      the first FAXWXXT motif did not. Compared to the VMC61, the 33-amino acid peptide
      corresponding to the C-terminus exhibited a similar binding affinity and a lower
      binding capacity.

PMID- 15848197
TI  - Gene expression and characterization of isoprene synthase from Populus alba.
AB  - Isoprene synthase cDNA from Populus alba (PaIspS) was isolated by RT-PCR. This
      PaIspS mRNA, which was predominantly observed in the leaves, was strongly induced
      by heat stress and continuous light irradiation, and was substantially decreased
      in the dark, suggesting that isoprene emission was regulated at the
      transcriptional level. The subcellular localization of PaIspS protein with green
      fluorescent protein fusion was shown to be in plastids. PaIspS expressed in
      Escherichia coli was characterized enzymatically: it had an optimum pH of
      approximately 8.0, and an optimum temperature 40 degrees C. Its preference for
      divalent cations for its activity was also studied.

PMID- 15848198
TI  - Molecular characterization of the first satellite DNA with CENP-B and CDEIII
      motifs in the bat Pipistrellus kuhli.
AB  - The centromere is an essential structure in the chromosomes of all eukariotes and
      is central to the mechanism that ensures proper segregation during mitosis and
      meiosis. The comparison of DNA sequence motifs, organization and kinetocore
      components from yeast to man is beginning to indicate that, although centromeres
      are highly variable DNA elements, a conserved pattern of sequence arrangement and
      function is emerging. We have identified and characterized the first satellite
      DNA (P.k.SAT) from microbat species Pipistrellus kuhli. The presence of mammalian
      CENP-B box and yeast CDEIII box could indicate the participation of P.k.SAT in
      centromere organization.

PMID- 15848199
TI  - Nitric oxide, cytochrome c oxidase and myoglobin: competition and reaction
      pathways.
AB  - It is relevant to cell physiology that nitric oxide (NO) reacts with both
      cytochrome oxidase (CcOX) and oxygenated myoglobin (MbO(2)). In this respect, it
      has been proposed [Pearce, L.L., et al. (2002) J. Biol. Chem. 277, 13556-13562]
      that (i) CcOX in turnover out-competes MbO(2) for NO, and (ii) NO bound to
      reduced CcOX is "metabolized" in the active site to nitrite by reacting with
      O(2). In contrast, rapid kinetics experiments reported in this study show that
      (i) upon mixing NO with MbO(2) and CcOX in turnover, MbO(2) out-competes the
      oxidase for NO and (ii) after mixing nitrosylated CcOX with O(2) in the presence
      of MbO(2), NO (and not nitrite) dissociates from the enzyme causing myoglobin
      oxidation.

PMID- 15848200
TI  - H2O2 activates Nox4 through PLA2-dependent arachidonic acid production in adult
      cardiac fibroblasts.
AB  - Stimulated production of reactive oxygen species (ROS) by plasma membrane
      associated nicotinamide adenine dinucleotide phosphate oxidases (Nox) in non
      phagocytic cells regulates a number of biological processes including growth,
      vessel tone, and oxygen sensing. The purpose of this study was to investigate
      H(2)O(2)-stimulated ROS production in primary adult cardiac fibroblasts (CF).
      Results demonstrate that CF express an H(2)O(2)-inducible oxidant generating
      system that is inhibitable by diphenylene iodonium (DPI) and sensitive to
      antioxidants. In addition to H(2)O(2), generation of ROS was stimulated potently
      by 1-oleoyl-2-acetyl-sn-glycerol (OAG) and arachidonic acid (AA) in a protein
      kinase C-independent manner. Pretreatment with arachidonyl trifluoromethyl ketone
      was nearly as effective as DPI at reducing H(2)O(2)- and OAG-stimulated oxidant
      generation indicating a central role for phospholipase A(2) (PLA(2)) in this
      signaling pathway. Co-stimulation with H(2)O(2) and OAG did not increase ROS
      generation as compared to OAG alone suggesting both agonists signal through a
      shared, rate-limited enzymatic pathway involving PLA(2). Co-stimulation with
      H(2)O(2) and AA had additive effects indicating these two agonists stimulate
      oxidant production through a parallel activation pathway. Reverse transcriptase
      coupled polymerase chain reaction and Western blotting demonstrate primary
      cardiac fibroblasts express transcripts and protein for Nox4, p22, p47, and p67
      phox. Transfections with Nox4 small inhibitory ribonucleic acid oligonucleotides
      or p22 phox antisense oligonucleotides significantly downregulated stimulated Nox
      activity. Inhibitors of nitric oxide synthases were without effect. We conclude
      adult CF express Nox4/p22 phox-containing oxidant generating complex activated by
      H(2)O(2), OAG, and AA through a pathway that requires activation of PLA(2).

PMID- 15848201
TI  - Microwave-assisted synthesis and anti-bacterial activity of some 2-amino-6-aryl-4
      (2-thienyl)pyrimidines.
AB  - Some novel 2-amino-6-aryl-4-(2-thienyl)pyrimidines were synthesized from 3-aryl-1
      thien-2-ylprop-2-en-1-ones and guanidine hydrochloride in presence of alkali by
      conventional heating in alcoholic medium and microwave heating in solvent-free
      conditions. The compounds were evaluated for in vitro anti-bacterial activity.
      The anti-bacterial data revealed that compounds 5a-e had better activity against
      tested gram-positive organisms than the reference ciprofloxacin and norfloxacin.
      However, the compounds were nearly inactive against gram-negative bacteria.
      Compounds 5c and e were the most active compounds against gram-positive bacteria.

PMID- 15848202
TI  - Synthesis and study of some new N-substituted imide derivatives as potential
      anticancer agents.
AB  - A new series of N-substituted imide derivatives have been synthesized by treating
      phthalic anhydride, naphthalic anhydride and their substituted derivatives with 2
      hydrazino-1-imidazoline hydrobromide, various para-substituted aryl amines,
      aminoglutethimide and 2,4-dinitrophenyl hydrazine. Compounds 9, 10, 12, 18, 19,
      23, 24 and 34-36 have been selected and screened for antineoplastic activity by
      National Cancer Institute, Bethesda, USA. Some newer aminoglutethimide
      derivatives 37-39 have also been prepared in order to study the effect of N
      substitution on its pharmacological profile for the treatment of carcinoma. These
      compounds (37-39) have exhibited weak inhibition of human placental aromatase as
      compared to aminoglutethimide.

PMID- 15848203
TI  - Structural modifications and antimicrobial activity of N-cycloalkenyl-2
      acylalkylidene-2,3-dihydro-1,3-benzothiazoles.
AB  - A series of N-cycloalkenyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles 5a-j,
      N-cycloalkyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles 8a-e, and N-alkyl-2
      acylalkylidene-2,3-dihydro-1,3-benzothiazoles 8f-h, were synthesized and tested
      for in vitro antibacterial and antifungal activities against four gram-positive
      and five gram-negative bacteria (Bacillus subtilis 6633, Enterococcus faecalis
      29212, Staphylococcus aureus 6538, Staphylococcus aureus 25923, Escherichia coli
      25922, Acinetobacter calcoaceticus a1, A. calcoaceticus a2, Pseudomonas
      aeruginosa 27835, Klebsiella oxytoca 49131), four yeast-like fungi and one fungus
      (Candida tropicalis 750, C. albicans 14053, C. albicans 10231, Cryptococcus
      laurentii 18803, and Saccharomyces cerevisiae). Microdilution broth and agar
      dilution methods were used for antimicrobial tests. The findings obtained showed
      that some of the tested compounds 5 and 8 were effective against some of the
      bacterial strains used, whereas, only compounds 8b-g exhibited a moderate
      antifungal activity against the yeast strains evaluated.

PMID- 15848204
TI  - Synthesis, biological studies and molecular modeling investigation of 1,3
      dimethyl-2,4-dioxo-6-methyl-8-(substituted) 1,2,3,4-tetrahydro [1,2,4]-triazolo
      [3,4-f]-purines as potential adenosine receptor antagonists.
AB  - A new series of potential adenosine receptor antagonists with a [1,2,4]-triazolo
      [3,4-f]-purine structure have been synthesized, and their affinities at the four
      adenosine receptor subtypes (A1, A2A, A2B and A3) have been evaluated. The design
      was based on the demonstrated approach to novel A3 adenosine receptor antagonists
      of adding a third ring to the xanthine structure. Unfortunately, all the
      synthesized compounds were completely inactive at all four adenosine receptor
      subtypes independently of their substitutions. Preliminary molecular modeling
      investigation has demonstrated that only a low degree of steric and electrostatic
      complementarity has been observed for all the new synthesized triazolo-purines
      with respect to other structurally related A3 receptor antagonists. This analysis
      yielded valuable information about structure-activity relationships and further
      design of potential adenosine receptor antagonists.

PMID- 15848205
TI  - Synthesis and antimalarial activity of sulfonamide chalcone derivatives.
AB  - A series of sulfonamide chalcone derivatives were synthesized and investigated
      for their abilities to inhibit beta-hematin formation in vitro and their activity
      against cultured Plasmodium falciparum parasites. Inhibition of beta-hematin
      formation was minimal in the aromatic ring of the chalcone moiety as it appeared
      for compounds 4b, 4d-f, and greatest with compounds 4g (IC50 0.48 microM) and 4k
      (IC50 0.50 microM) with a substitution of 3,4,5-trimethoxyl and 3-pyridinyl,
      respectively. In this study, the most active compound resulted 1[4'-N(2'',5''
      dichlorophenyl) sulfonyl-amidephenyl]-3-(4-methylphenyl)-2-propen-1-one 4i,
      effective as antimalarial by the inhibition of cultured P. falciparum parasites
      (1 microM). These studies open up the novel possibility of development of
      sulfonamide derivatives as antimalarials that target beta-hematin formation and
      the inhibition of the development of cultured P. falciparum parasites, which
      should help delay the rapid onset of resistance to drugs acting at only a single
      site. Results with these assays suggest that chalcones exert their antimalarial
      activity via multiple mechanisms.

PMID- 15848206
TI  - Docking of 6-chloropyridazin-3-yl derivatives active on nicotinic acetylcholine
      receptors into molluscan acetylcholine binding protein (AChBP).
AB  - The crystal structure of Acetylcholine Binding Protein (AChBP), homolog of the
      ligand binding domain of nAChR, has been used as model for computational
      investigations on the ligand-receptor interactions of derivatives of 6
      chloropyridazine substituted at C3 with 3,8-diazabicyclo[3.2.1]octane, 2,5
      diazabicyclo[2.2.1]heptane and with piperazine and homopiperazine, substituted or
      not at N4. The ligand-receptor complexes have been analyzed by docking techniques
      using the binding site of HEPES complexed with AChBP as template. The good
      relationship between the observed binding affinity and the calculated docking
      energy confirms that this model provides a good starting point for understanding
      the binding domain of neuronal nicotinic receptors. An analysis of the possible
      factors significant for the ligand recognition has evidenced, besides the cation
      pi interaction, the distance between the chlorine atom of the pyridazinyl group
      and the carbonylic oxygen of Leu B112 as an important parameter in the modulation
      of the binding energy.

PMID- 15848207
TI  - Analgesic potential of marrubiin derivatives, a bioactive diterpene present in
      Marrubium vulgare (Lamiaceae).
AB  - Marrubiin, a furane labdane diterpene, is the main analgesic compound present in
      Marrubium vulgare, a medicinal plant used in Brazil and other countries to treat
      several ailments. Considering its important pharmacological action, as well as
      its high yield, some structural modifications were performed in order to obtain
      more active compounds. Success was obtained in reducing the lactonic function, in
      the formation of marrubiinic acid and two esterified derivatives, which exhibited
      significant analgesic effect against the writhing test in mice. Marrubiinic acid
      showed better activity and excellent yield, and its analgesic effect was
      confirmed in other experimental models of pain in mice, suggesting its possible
      use as a model to obtain new and potent analgesic agents.

PMID- 15848208
TI  - Synthesis and biological evaluation of a new class of acyl derivatives of 3-amino
      1-phenyl-4,5-dihydro-1H-pyrazol-5-one as potential dual cyclooxygenase (COX-1 and
      COX-2) and human lipoxygenase (5-LOX) inhibitors.
AB  - A series of acyl derivatives of 3-amino-1-phenyl-4,5-dihydro-1H-pyrazol-5-one as
      potential human 5-LOX and COX 1 and COX-2 inhibitors structurally related to the
      1-phenyl-3-pyrazolidinone (phenidone, 1) have been synthesized and the activity
      against COX-1, COX-2 and human 5-LOX enzymes has been evaluated. All the
      derivatives showed poor activity against enzymes. These data, together with our
      previous studies, indicated that phenidone and related compounds are not suitable
      as human 5-LOX inhibitors and that pyrazoline nucleus should not be considered a
      good scaffold for inhibitors of human 5-LOX enzyme, suggesting the necessity to
      revisit the proposed mechanism of action of phenidone (1) in human models.

PMID- 15848209
TI  - Ratio spectra derivative spectrophotometry for the determination of furosemide
      and spironolactone in a capsule formulation.
AB  - The determination of furosemide and spironolactone in a capsule formulation has
      been investigated using techniques such as Vierordt's method and derivative
      spectroscopy dA/d lambda and d2A/d lambda2 applying the zero-crossing technique
      following reported methods. In our hands, using standard mixtures, these methods
      gave unreliable results. We have therefore investigated the use of ratio spectra
      derivative spectrophotometry for this determination. The technique of ratio
      spectra derivative spectrophotometry was developed in 1990, and has recently been
      used for a number of analyses of co-formulated products. The method was applied
      to the analysis of standard mixtures of the two drugs and the combined contents
      of 20 capsules resulting in values (mean +/- standard deviation) of 102.1 +/-
      1.9% and 101.4 +/- 4.0% of the stated content for furosemide and spironolactone,
      respectively. Similarly, the analysis of individual capsules resulted in values
      of 101.5 +/- 1.6% and 102.2 +/- 1.4% of the stated content for furosemide and
      spironolactone, respectively.

PMID- 15848210
TI  - Formulation and in vitro evaluation of prednisolone buccoadhesive tablets.
AB  - In this research, the effect of mucoadhesive polymers such as hydroxyl propyl
      methyl cellulose (HPMC) with viscosity grade 60 and 500 mPas, sodium carboxy
      methyl cellulose (NaCMC) and carbopol 934 (Cp 934) alone or in combination with
      each other on the release profile of prednisolone was studied and mucoadhesion
      strength of these buccoadhesive formulations was evaluated. The results showed
      that the release of prednisolone from HPMC with viscosity grade 60 mPas and Cp
      934 alone was fast and their mucoadhesion strengths was low. On the other hand,
      the release rates of prednisolone from the HPMC viscosity grade 500 mPas and
      NaCMC and mucoadhesion strengths were moderate and suitable. The results showed
      that with different blends of HPMC viscosity grade 500 mPas or NaCMC and Cp 934
      with increasing in HPMC or NaCMC/Cp 934 ratio a remarkable decrease in the rate
      of drug release and an appreciable increase in the mucoadhesion strength was
      observed. Except from the formulations prepared with HPMC viscosity grade 60 and
      500 mPas, other formulation had more fluctuations in release profiles and their
      kinetics of release were not fitted to zero order model.

PMID- 15848211
TI  - Liquid chromatographic-mass spectrometric method for the determination of
      fluoxetine and norfluoxetine in human plasma: application to clinical study.
AB  - A selective, sensitive, simple, and rapid method for the simultaneous
      determination of fluoxetine (FL) and norfluoxetine (nor-FL) was developed and
      validated, and further applied to analyze plasma samples obtained from FL-treated
      patients with Parkinson disease (n = 18). After one step liquid-liquid extraction
      with ethyl acetate, plasma samples were chromatographed on a C8 column. The
      mobile phase was acetate buffer and acetonitrile (40:60 v/v). Determination of FL
      and nor-FL was performed with MS detection in selective ion monitoring (SIM)
      mode, so the other components did not interfere with this assay. FL, nor-FL and
      flumazenil as internal standard were eluted in 6 min. Recoveries ranged from 89.7
      to 96.6% and from 80.2 to 85.3% for FL and nor-FL, respectively. The limit of
      quantitation under described conditions was 2.5 microg/l for FL and 10 microg/l
      for nor-FL. The method was found to be reproducible with coefficient of variation
      less than 9%. The parameters of the method were found to be acceptable to enable
      its routine use for clinical studies. The method was employed to analyze the
      Parkinsonian patients' plasma samples. A great deviation in plasma concentrations
      of FL and nor-FL found among 18 studied patients indicates high pharmacokinetic
      variability of the drug. Obtained results also indicate absence of the influence
      of Parkinson disease on the drug disposition.

PMID- 15848212
TI  - Application of stability-indicating HPTLC method for quantitative determination
      of metadoxine in pharmaceutical dosage form.
AB  - A sensitive, selective, precise and stability-indicating high-performance thin
      layer chromatographic method for analysis of metadoxine both as a bulk drug and
      in formulations was developed and validated. The method employed TLC aluminium
      plates precoated with silica gel 60F-254 as the stationary phase. The solvent
      system consisted of acetone-chloroform-methanol-ammonia (7.0:4.0:3.0:1.2,
      v/v/v/v). Densitometric analysis of metadoxine was carried out in the absorbance
      mode at 315 nm. This system was found to give compact spots for metadoxine (Rf
      value of 0.45+/-0.02, for six replicates). Metadoxine was subjected to acid,
      alkali and neutral hydrolysis, oxidation, dry and wet heat treatment and photo
      and UV degradation. The drug undergoes degradation under all stress conditions.
      Also, the degraded products were well resolved from the pure drug with
      significantly different Rf values. The method was validated for linearity,
      precision, robustness, LOD, LOQ, specificity and accuracy. Linearity was found to
      be in the range of 100-1500 ng/spot with significantly high value of correlation
      coefficient r2=0.9997+/-1.02. The linear regression analysis data for the
      calibration plots showed good linear relationship with r2=0.9999+/-0.58 in the
      working concentration range of 200-700 ng/spot. The mean value of slope and
      intercept were 0.11+/-0.04 and 18.73+/-1.89, respectively. The limits of
      detection and quantitation were 50 and 100 ng/spot, respectively. Statistical
      analysis proves that the method is repeatable and specific for the estimation of
      the said drug. As the method could effectively separate the drug from its
      degradation products, it can be employed as a stability-indicating one. Moreover,
      the proposed HPTLC method was utilized to investigate the kinetics of acid and
      base degradation process. Arrhenius plot was constructed and activation energy
      was calculated respectively for acid and base degradation process.

PMID- 15848213
TI  - Enhancement of dissolution rate of piroxicam using liquisolid compacts.
AB  - Piroxicam is a poorly soluble, highly permeable drug and the rate of its oral
      absorption is often controlled by the dissolution rate in the gastrointestinal.
      The poor dissolution rate of water-insoluble drugs is still a major problem
      confronting the pharmaceutical industry. There are several techniques to enhance
      the dissolution of poorly soluble drugs. Among them, the technique of liquisolid
      compacts is a promising technique towards such a novel aim. In this study, the
      dissolution behaviour of piroxicam from liquisolid compacts was investigated in
      simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH
      7.2). To this end, several liquisolid tablets formulations containing various
      ratios of drug:Tween 80 (ranging from 10% to 50% w/w) were prepared. The ratio of
      microcrystalline cellulose (carrier) to silica (coating powder material) was kept
      constant in all formulations. The results showed that liquisolid compacts
      demonstrated significantly higher drug release rates than those of conventionally
      made (capsules and directly compressed tablets containing micronized piroxicam).
      This was due to an increase in wetting properties and surface of drug available
      for dissolution.

PMID- 15848214
TI  - Effect of donepezil and lercanidipine on memory impairment induced by
      intracerebroventricular streptozotocin in rats.
AB  - Intracerebroventricular (ICV) injection of streptozotocin (STZ) causes cognitive
      impairment in rats. ICV STZ is known to impair cholinergic neurotransmission by
      decreasing choline acetyltransferase (ChAT) levels, glucose and energy metabolism
      in brain and synthesis of acetyl CoA. However, no reports are available regarding
      the cholinesterase inhibitors in this model. In aging brain, reduced energy
      metabolism increases glutamate release, which is blocked by L-type calcium
      channel blockers. These calcium channel blockers have shown beneficial effects on
      learning and memory in various models of cognitive impairment. The present study
      was designed to investigate the influence of chronic administration of donepezil
      (cholinesterase inhibitor, 1 and 3 mg/kg) and lercanidipine (L-type calcium
      channel blocker, 0.3 and 1 mg/kg) on cognitive impairment in male Sprague-Dawley
      rats injected twice with ICV STZ (3 mg/kg) bilaterally on days 1 and 3. ICV STZ
      injected rats developed a severe deficit in learning and memory indicated by
      deficits in passive avoidance paradigm and elevated plus maze as compared to
      control rats. Cholinesterase activity in brain was significantly increased in ICV
      STZ injected rats. Donepezil dose-dependently inhibited cholinesterase activity
      and improved performance in memory tests at both the doses. Lercanidipine (0.3
      mg/kg) showed significant improvement in memory. When administered together, the
      effect of combination of these two drugs on memory and cholinesterase activity
      was higher than that obtained with either of the drugs when used alone.

PMID- 15848215
TI  - Effect of endothelin antagonist (TAK-044) on cerebral ischemic volume, oxidative
      stress markers and neurobehavioral parameters in the middle cerebral artery
      occlusion model of stroke in rats.
AB  - Stroke causes brain injury in millions of people world wide each year. Despite
      the enormity of problem, currently there is no established therapy, which can
      restore the blood flow at infracted area and also improve the neurological
      deficit. The present study was carried out to investigate the effect of an
      endothelin antagonist (TAK-044) in middle cerebral artery (MCA) occlusion model
      of acute ischemic stroke in rats. Male Wistar rats were pretreated with TAK-044
      (5 mg/kg, i.p.) for 7 days and thereafter subjected to focal ischemia by
      occlusion of MCA using intraluminal thread for two hours. 30 min after
      reperfusion the animals were subjected to diffusion-weighted imaging (DWI) for
      assessment of protective effect. Twenty-four hours later the motor performance
      was tested and subsequently the animals were sacrificed for estimation of markers
      of oxidative stress; malondialdehyde (MDA), glutathione (GSH) and superoxide
      dismutase (SOD). Control group received vehicle (saline) and similar experimental
      protocol was followed. In the TAK-044 pretreated group, percent hemispheric
      lesion area (% HLA) in DWI was significantly attenuated 17.5 +/- 0.5% as compared
      to control group 61.2 +/- 5.9%. Significant motor impairment, with significant
      elevated levels of MDA, decrease in GSH and SOD were observed in the vehicle
      treated MCA occluded rats. Pretreatment with TAK-044 prevented the motor
      impairment and significantly reversed the changes in markers of oxidative stress
      (MDA, GSH and SOD). In addition to well-known vasodilatory effect, TAK-044 has
      recently been documented to have antioxidant and anti-inflammatory properties.
      These effects can contribute to the protection afforded by TAK-044 in the present
      study.

PMID- 15848216
TI  - Inhibition of hypoxia-induced proliferation and collagen synthesis by vasonatrin
      peptide in cultured rat pulmonary artery smooth muscle cells.
AB  - The aim of the present research is to investigate the effects of vasonatrin
      peptide (VNP) on hypoxia-induced proliferation and collagen synthesis in
      pulmonary artery smooth muscle cells (PASMCs). Smooth muscle cells isolated from
      rat pulmonary artery were cultured and used at passages 3-5. Cell proliferation
      and collagen synthesis were evaluated by cell counts, [(3)H] thymidine and [(3)H]
      proline incorporation. The results showed that cells exposed to hypoxia for 24 h
      exhibited a significant increase in [(3)H] thymidine (93%) and [(3)H] proline
      (52%) incorporation followed by a significant increase in cell number (47%) at 48
      h in comparison with the respective normoxic controls. VNP reduced hypoxia
      stimulated increase in cell proliferation in a concentration-dependent manner
      from 10(-8) to 10(-6) mol/L and attenuated hypoxia-induced collagen synthesis
      ranging from 10(-6) to 10(-5) mol/L, which is similar to but more potent than
      both ANP and CNP. The action of VNP on PASMCs was mimicked by 8-bromo-cGMP (10(
      4) mol/L, the membrane-permeable cGMP analog), and blocked by HS-142-1 (2 x 10(
      5) mol/L), the particulate guanylyl cyclase-coupled natriuretic peptide receptor
      antagonist, or KT-5823 (10(-6) mol/L), the cGMP-dependent protein kinase (PKG)
      inhibitor. The results suggest that VNP inhibits hypoxia-stimulated proliferation
      and collagen synthesis in cultured rat PASMCs via particulate guanylyl cyclase
      coupled receptors through cGMP/PKG dependent mechanisms.

PMID- 15848217
TI  - The plant polyphenol butein inhibits testosterone-induced proliferation in breast
      cancer cells expressing aromatase.
AB  - Chalcones are precursor compounds for flavonoid synthesis in plants, and they can
      also be synthesized in laboratory. Previous study has documented some of the
      pharmacological applications of these compounds. Estrogen has long been
      associated with the initiation and promotion of breast cancer. Inhibiting
      estrogen synthesis can be effective in the prevention and treatment of the
      disease. Since most breast cancers received estrogen supplied from local tissues,
      we employed a breast cancer cell line expressing aromatase to screen for the
      inhibitory potentials of five hydroxychalcones, i.e. 2-hydroxychalcone, 2'
      hydroxychalcone, 4-hydroxychalcone, 4,2',4'-trihydroxy-chalcone
      (isoquiritigenin), 3,4,2',4'-tetrahydroxychalcone (butein). In the preliminary
      results, butein was found to be the strongest inhibitor among the tested
      compounds, and its IC(50) value was 3.75 microM. Subsequent enzyme kinetic study
      revealed that butein acted on aromatase with a mixed type of inhibition and the
      K(i) value was determined to be 0.32 microM. Cell proliferation assay indicated
      that the cell number increased by 10 nM-testosterone treatment was significantly
      reduced by 5 microM butein, and the administration of flutamide could not reverse
      the effect. The present study illustrated that butein was an aromatase inhibitor
      and a potential natural alternative for the chemoprevention or therapy of breast
      cancer.

PMID- 15848218
TI  - Heterogeneous expression of connexin 43 in the myocardium of rabbit right
      ventricular outflow tract.
AB  - The right ventricular outflow tract (RVOT) has been demonstrated as an important
      focus in idiopathic ventricular arrhythmias. However, the role of the gap
      junction in this region in arrhythmic events has not been fully investigated. The
      purpose of this study was to evaluate the expression and distribution of the gap
      junction protein connexin 43 (Cx43) in the myocardium of the RVOT area of normal
      adult rabbits. Tissue samples were obtained from 6 regions of normal rabbit
      heart, i.e. the left ventricle (LV) free wall, the LV papillary muscle, the RVOT
      free wall, and the RVOT septum which was subdivided into the RV side, the central
      layer, and the LV side. Immunohistochemical analysis was performed to investigate
      the characteristics of Cx43 distribution in the RVOT area. In the LV free wall
      and papillary muscle, Cx43 was abundantly, homogeneously, and approximately
      equally expressed in end-to-end- and side-to-side intercellular connections. In
      the free wall of the RVOT, Cx43 expression was poor compared to both these LV
      regions and side-to-side cell connections were predominant. Cx43 was as richly
      and homogeneously distributed in the central layer and LV side of the RVOT septum
      as in the two LV regions. However, in the RV side of the RVOT septum, its
      distribution was scant and an unstained area was noted. The heterogeneous
      expression of Cx43 in the RVOT area may serve as substrate for idiopathic
      ventricular arrhythmia.

PMID- 15848219
TI  - Role of p38 in nitric oxide synthase and cyclooxygenase expression, and nitric
      oxide and PGE2 synthesis in human gingival fibroblasts stimulated with
      lipopolysaccharides.
AB  - Periodontal disease, a gingival inflammatory disease caused by gram-negative
      bacteria, is the main cause of tooth loss. Lipopolysaccharides (LPS) present in
      bacterial cell walls induce human gingival fibroblasts' production of pro
      inflammatory cytotoxins such as IL-1beta and TNFalpha. The goal of this study was
      to determine p38 role in the expression of inducible nitric oxide synthase enzyme
      (i-NOS) and cyclooxygenase (COX-2), as well as in PGE(2) and nitric oxide
      synthesis in human gingival fibroblasts challenged with LPS. We found that
      lipopolysaccharides induced a rapid and significant increase in p38
      phosphorylation. After interruption of p38 transduction pathway by pre-treatment
      with inhibitor SB203580, no response to stimulation with LPS was observed; i-NOS
      expression and nitric oxide synthesis was completely blocked. However, p38
      inhibition only partially blocked COX-2 expression and PGE2 synthesis. We
      conclude that p38 is critically involved in i-NOS induction, and that it
      participates in COX-2 expression and in PGE2 synthesis.

PMID- 15848220
TI  - Relaxation of canine corporal smooth muscle relaxation by ginsenoside saponin Rg3
      is independent from eNOS activation.
AB  - It has been reported that nitric oxide (NO) is involved in the relaxation
      mechanism of ginsenoside saponin in various smooth muscle in experimental
      animals. Although ginsenoside Rg(3) showed both endothelium-dependent and 
      independent component relaxation in vascular smooth muscle, the action mechanism
      of the relaxation of corporal muscle is not clear. We, thus, investigated the
      relaxation mechanism of ginsenoside Rg(3) using isolated canine corpus
      cavernosum. Ginsenoside Rg(3) concentration-dependently relaxed the canine corpus
      cavernosum that had been contracted by phenylephrine (PE), in which IC(50) was
      1.68 x 10(-5) g/ml. Ginsenoside Rg(3) significantly (P < 0.05) potentiated
      acetylcholine (ACh)-induced relaxation in endothelium intact corpus cavernosum.
      Methylene blue (MB) but not N(omega)-nitro-L-arginine methylester (L-NAME) or ODQ
      (1H-[1,2,4]oxadiazol-[4,3-]quinoxsalin-1-one) modified the dose-response curve of
      ginsenoside Rg(3). Ginsenoside Rg(3) also significantly potentiated relaxation
      response to UV light in the presence of streptozotocin (STZ), which was almost
      completely (P < 0.01) blocked by ODQ. Ginsenoside Rg(3) concentration-dependently
      inhibited corporal phosphodiesterases (PDE), which resulted in increase of cyclic
      adenosine monophosphate (cAMP) as well as cyclic guanosine monophosphate (cGMP)
      contents in corporal smooth muscles. MB inhibited the accumulation of cGMP but
      not cAMP by ginsenoside Rg(3). These results indicate that mechanism responsible
      for the relaxation by ginsenoside Rg(3) is not by stimulating endothelial nitric
      oxide synthase (eNOS) of the canine corporal smooth muscle but by increasing
      cyclic nucleotide levels through PDE inhibition.

PMID- 15848221
TI  - Enhancement of fentanyl antinociception by subeffective doses of nitroparacetamol
      (NCX-701) in acute nociception and in carrageenan-induced monoarthritis.
AB  - We have reported that subanalgesic doses of new generation non-steroidal anti
      inflammatory drugs (NSAIDs) enhance the antinociceptive activity of the mu-opiate
      fentanyl, and the duration of its effect, in acute nociception. Since this
      therapy is intended for situations of hyperalgesia, we have compared the
      antinociceptive activity of fentanyl in the absence and in the presence of
      subeffective doses of NCX-701 (nitroparacetamol) in normal animals and in animals
      with carrageenan-induced monoarthritis. Subanalgesic dose of NCX-701 did not
      modify any of the nociceptive responses on its own but reduced the ID50 of
      fentanyl more than two-fold in both the normal and sensitized states. When
      administered alone, full recovery from fentanyl was always observed within 15 to
      20 minutes, however, full recovery was not observed in the presence of NCX-701.
      Naloxone was unable to reverse the effect, suggesting a possible reduction of
      other opiate-mediated secondary effects. We therefore studied the possibility
      that combining administration of fentanyl and nitroparacetamol (NCX-701) would
      reduce the development of acute tolerance to fentanyl in behavioral experiments.
      Acute tolerance to fentanyl in behavioral nociceptive reflexes was developed
      within 72 h after the constant infusion of the drug, whereas in animals treated
      with small doses of NCX-701 tolerance was not observed. In summary, our results,
      both in normal animals and in animals with hyperalgesia, show that fentanyl
      antinociception can be strongly potentiated with subanalgesic doses of the NSAID
      NCX-701 and that the development of acute tolerance to fentanyl in normal animals
      is prevented by this combination of drugs.

PMID- 15848222
TI  - Akt regulates thrombin-induced HSP27 phosphorylation in aortic smooth muscle
      cells: function at a point downstream from p38 MAP kinase.
AB  - We previously reported that p38 MAP kinase takes part in thrombin-induced HSP27
      phosphorylation in aortic smooth muscle A10 cells. In the present study, we
      investigated whether Akt is involved in the phosphorylation of HSP27 and the role
      of adenylyl cyclase-cAMP system. Thrombin time-dependently induced the
      phosphorylation of heat shock protein 27 (HSP27) and Akt in aortic smooth muscle
      A10 cells. SB203580, a p38 MAP kinase inhibitor, significantly suppressed the
      thrombin-induced phosphorylation of Akt and the Akt inhibitor suppressed the
      phosphorylation of HSP27. Furthermore, the thrombin-induced phosphorylation of
      HSP27, p38 MAP kinase and Akt were decreased by dibutyryl-cAMP (DBcAMP). These
      results strongly suggest that Akt functions the thrombin-induced phosphorylation
      of HSP27 at a point downstream from p38 MAP kinase in aortic smooth muscle cells
      and the adenylyl cyclase-cAMP system is upstream regulator of the HSP27
      phosphorylation in these cells.

PMID- 15848223
TI  - Apolipoprotein A-I-dependent cholesterol esterification in patients with
      rheumatoid arthritis.
AB  - Growing evidence suggests that atherogenesis is associated with inflammation or
      defective removal of cholesterol excess from peripheral cells. Apolipoprotein A-I
      [ApoA-I] activates the enzyme Lecithin-Cholesterol Acyl-Transferase to esterify
      cell cholesterol for transport to liver. Haptoglobin [Hpt] was previously found
      able to bind ApoA-I, and suggested to reduce the enzyme activation. The aim of
      this study was to demonstrate that enhanced levels of Hpt, as present during
      inflammation, are associated with low enzyme activity and increased thickness of
      the arterial wall. Enzyme activity and Hpt concentration were analysed in
      patients with rheumatoid arthritis having the same plasma levels of antioxidants
      (ascorbate, urate, alpha-tocopherol, retinol) or oxidation markers
      (nitrotyrosine, lipoperoxide) of healthy subjects. Cholesterol esterification,
      determined as ratio of cholesteryl esters with cholesterol in high-density
      lipoproteins, was lower in patients than in controls, and negatively correlated
      with the intima-media wall thickness of the common carotid. The ratio of Hpt with
      ApoA-I was negatively correlated with the enzyme activity, while positively
      correlated with intima-media wall thickness. The results suggest that high Hpt
      levels might severely impair the enzyme activity, thus contributing to
      cholesterol accumulation in vascular cells, and lesion formation in the
      endothelium.

PMID- 15848224
TI  - Plasmid vectors for protein production, gene expression and molecular
      manipulations in Aspergillus niger.
AB  - We constructed three sets of plasmids for use in Aspergillus niger. These
      plasmids were assembled using various combinations of a series of modular DNA
      cassettes that included a selectable marker, pyrG, derived from Aspergillus
      nidulans; two promoter regions for directing protein expression; a cassette
      derived from the AMA1 replicator sequence to support autonomous replication; and
      a reporter gene based on the A. niger lacA gene. One set included integrating and
      autonomously replicating plasmids for the expression of homologous and
      heterologous proteins. The second was a set of autonomously replicating plasmids,
      with a secreted beta-galactosidase encoding reporter gene, for studying gene
      regulation events. The third set included pyrG-derived gene-blaster cassettes
      suitable for genome manipulation by targeted gene replacement.

PMID- 15848225
TI  - Distribution of Bacillus megaterium QM B1551 plasmids among other B. megaterium
      strains and Bacillus species.
AB  - Bacillus megaterium QM B1551 contains seven plasmids. Two are small rolling
      circle plasmids and five are theta-replicating plasmids with cross-hybridizing
      replicons that define a new family of very homologous yet compatible theta
      replicons. Previous sequencing of several of the plasmids has shown genes with
      high similarity to those on the genomes and plasmids of other Gram-positive
      bacteria. To test the possible distribution of these plasmids, nine other B.
      megaterium strains and 20 other Bacillus or related species were tested for the
      presence of similar replicons, and specific flanking DNA by both hybridization
      and PCR. The theta replicons were widespread among the B. megaterium strains, and
      two had one or more of the rolling circle plasmids, but none of the plasmid
      replicon regions were observed in the other Bacillus or related species. It
      appears from the data that even though some plasmids carry genes suggesting
      horizontal transfer, their replicons seem to be unique to B. megaterium, or
      rarely present in related species.

PMID- 15848226
TI  - Sequence of the 68,869 bp IncP-1alpha plasmid pTB11 from a waste-water treatment
      plant reveals a highly conserved backbone, a Tn402-like integron and other
      transposable elements.
AB  - To analyse the significance of conjugative broad-host-range IncP-1alpha plasmids
      for the spread of antibiotic resistance determinants in waste-water treatment
      plants we isolated and characterised five different IncP-1alpha plasmids from
      bacteria of activated sludge and the final effluents of a municipal waste-water
      treatment plant. These plasmids mediate resistance to ampicillin, cefaclor,
      cefuroxime, gentamicin, kanamycin, spectinomycin, streptomycin, tetracycline,
      tobramycin, and trimethoprim. The complete 68,869 bp DNA-sequence of the IncP
      1alpha plasmid pTB11 was determined. The pTB11 backbone modules for replication
      (Rep), mating pair formation (Trb), multimer resolution (Mrs), post-segregational
      killing (Psk), conjugative DNA-transfer (Tra), plasmid control (Ctl), and stable
      maintenance and inheritance (KilA, KilE, and KilC) are highly conserved as
      compared to the 'Birmingham' IncP-1alpha plasmids. In contrast to the
      'Birmingham' plasmids pTB11 carries an insert of a Tn402-derivative integrating a
      class 1 integron in the intergenic region between the multimer resolution operon
      parCBA and the post-segregational killing operon parDE. The integron comprises
      the resistance gene cassettes oxa2 (beta-lactamase), aacA4 (aminoglycoside-6'N
      acetyltransferase), and aadA1 (aminoglycoside-3'-adenylyltransferase) and a
      complete tniABQR transposition module. Integron-specific sequences were also
      identified on other IncP-1alpha plasmids analysed in this work. In contrast to
      the 'Birmingham' plasmids the pTB11 tetracycline resistance module carries a pecM
      and a pncA-like gene downstream of the tetracycline resistance gene tetA and
      contains an insertion of the new insertion sequence element ISTB11. The
      transposable elements IS21 and Tn1 which disrupted, respectively, orf7 and klcB
      on the 'Birmingham' plasmids are not present on pTB11. Identification of IncP
      1alpha plasmids in bacteria of the waste-water treatment plant's final effluents
      indicates that bacteria carrying these kind of plasmids are released into the
      environment.

PMID- 15848227
TI  - Cloning and characterization of a region responsible for the maintenance of
      megaplasmid pTAV3 of Paracoccus versutus UW1.
AB  - Using cointegrate formation, we constructed a basic replicon of the
      megaplasmid/mini-chromosome pTAV3 of Paracoccus versutus UW1. It is composed of
      two adjacent modules, responsible for plasmid replication (rep) and partitioning
      (par). Functional analysis of the par region identified a determinant of
      incompatibility (inc2), whose presence is crucial for proper partitioning (the
      partitioning site). Database searches revealed that the only known replicon with
      significant homology to that of pTAV3 is encoded by the chromosome cII of
      Rhodobacter sphaeroides 2.4.1. Incompatibility studies showed that closely
      related basic replicons are also encoded by megaplasmids (above 400 kb) harbored
      by four strains of P. pantotrophus. Basic replicons of the pTAV3-type are able to
      maintain large bacterial genomes, therefore they appear to be good candidates for
      the construction of vectors specific for Alphaproteobacteria.

PMID- 15848228
TI  - TnXO1, a germination-associated class II transposon from Bacillus anthracis.
AB  - Bacillus anthracis harbours two virulence plasmids, pXO1 (182 kb) and pXO2 (95
      kb). Whereas pXO2 harbours the cap operon coding for the capsule, pXO1 contains
      the pag, lef, and cya genes coding for protective antigen, lethal, and oedema
      factors, respectively, as well as the atxA regulatory gene. These genes are
      located within a 44.8 kb long pathogenicity island flanked by insertion
      sequences. Here, we describe the presence in the same plasmid region of an 8679
      bp genetic element displaying the structural features of a class II cointegrative
      transposon. This element, named TnXO1, bears a transposase and a site-specific
      recombinase and is delineated by 38 bp terminal inverted repeats sequences
      similar to those of other members of this group of transposons. A putative res
      site has been identified in the 200 bp region between these genes. Interestingly,
      TnXO1 also contains the gerX operon involved in the germination of B. anthracis
      spores within phagocytic cells. Such close association of a mobile DNA structure
      with known virulence determinants in a pathogen further prompted us to look for
      the presence of this transposable element in other members of the Bacillus cereus
      sensu lato group. No instance of TnXO1 was detected outside of B. anthracis in
      PCR experiments, although it was found to be present in the genome sequence draft
      of one strain of B. cereus which has recently been shown to harbour a plasmid
      almost identical to pXO1.

PMID- 15848229
TI  - Molecular characterization of a DNA fragment carrying the basic replicon of
      pTUC100, the natural plasmid encoding the peptide antibiotic microcin J25 system.
AB  - The Escherichia coli plasmid pTUC100 encodes production of, and immunity to, the
      peptide antibiotic microcin J25. In the present study, an approximately 8-kb
      fragment immediately adjacent to the previously sequenced microcin region was
      isolated and its DNA sequence was determined. The main features of the newly
      characterized region are: (i) a basic replicon which is almost identical to that
      of the RepFIIA plasmid R100; (ii) two ORFs with 96% identity to two ORFs of
      unknown function on pO157, a large plasmid harbored by enterohemorragic E. coli,
      and a large ORF which does not show significant homology to any other reported
      nucleotide or protein sequence; and (iii) two intact insertion sequences, IS1294
      and IS1. Sequence analysis, as well as that of the G+C content of both the 8-kb
      fragment and the previously sequenced microcin locus, lead us to propose that
      plasmid pTUC100 is a composite structure assembled from DNA elements from various
      sources.

PMID- 15848230
TI  - A novel plasmid (pEMCJH03) isolated from moraxella catarrhalis possibly useful as
      a cloning and expression vector within this species.
AB  - A preliminary screening study of six Moraxella catarrhalis isolates from primary
      school children in the Netherlands identified a small 3.5 kb plasmid (pEMCJH03),
      containing four open reading frames, which encoded three mobilizing and one
      replicase protein. Insertion of a kanamycin containing transposon (yielding
      pEMCJH04) allowed selection and isolation of the plasmid in Escherichia coli.
      Natural transformation of pEMCJH04 into M. catarrhalis was successful for 25%
      (3/12) of non-isogenic isolates, with no link between (lack of) transformability
      and genetic lineage or (lack of) transformability and complement phenotype,
      though the transformation efficiency was found to be rather low at approximately
      615CFU/microg (range=60-1040CFU/microg ). This is only the second publication
      detailing a plasmid isolated from this important respiratory pathogen, and the
      ability to clone and express foreign proteins in M. catarrhalis using pEMCJH04
      could help in the development of a vaccine expression vector, as well as
      providing a useful tool for studying promoter activity and in complementation
      studies of gene knockout mutants.

PMID- 15848231
TI  - Epitope-tagging vectors for the expression and detection of recombinant proteins
      in mycobacteria.
AB  - New tools are required to study the growing number of uncharacterised genes
      derived from genome sequence projects that are specific to bacterial pathogens
      such as Mycobacterium tuberculosis. We have developed a series of vectors that
      permit the specific detection of recombinant proteins expressed in mycobacterial
      species. Gene expression in these vectors is driven by the strong hsp60 promoter
      of Mycobacterium bovis BCG and detection of expressed products is facilitated by
      C-terminal fusion of residues 409-419 of the human c-myc proto-oncogene. Using
      the M. tuberculosis Ag85B as a reporter of gene expression, we demonstrate that
      the vectors permit the specific detection of recombinant products expressed in
      the host species M. bovis BCG. BCG over-expressing Ag85B was a potent inducer of
      Ag85B-specific T cells in immunised mice, indicating that the C-terminal c-myc
      tag did not alter the characteristics of the recombinant protein. The versatility
      of the epitope-tagging vectors was demonstrated by the efficient secretion and
      detection of recombinant products in BCG. The vectors described in this study
      will facilitate the expression of foreign proteins in mycobacterial host systems.

PMID- 15848232
TI  - Highly efficient protein expression and purification using bacterial hemoglobin
      fusion vector.
AB  - Recently developed bacterial hemoglobin (VHb) fusion expression vector has been
      widely used for the production of many target proteins due to its distinctive
      properties of expressing fusion protein with red color which facilitates
      visualization of the steps in purification, and increasing solubility of the
      target proteins. However, after intensive use of the vector, several defects have
      been found. In this report, we present a modified VHb fusion vector (pPosKJ) with
      higher efficiency, in which most of the defects were eliminated. First, it was
      found that thrombin protease often digests target protein as well as inserted
      thrombin cleavage site, so it was replaced by a TEV cleavage site for more
      specific cleavage of VHb from target protein. Second, a glycine-rich linker
      sequence was inserted between 6x his-tag and VHb to improve the affinity of 6x
      his-tag to Ni-NTA resin, resulting in higher purity of eluted fusion protein.
      Third, EcoRI and XhoI restriction sites located elsewhere in the vector were
      removed to make these restriction sites available for the cloning of target
      protein coding genes. A pPosKJ vector was fully examined with an anti-apoptotic
      BCL-2 family member of Caenorhabditis elegans, CED-9. A C-terminal VHb fusion
      expression vector (pPosKJC) was also constructed for stable expression of target
      proteins that may be difficult to express with an N-terminal fusion. Vaccinia
      related kinase 1 (VRK1) was also successfully expressed and purified using the
      vector with high yield. Taken together, we suggest that the VHb fusion vector may
      be well suited for high-throughput protein expression and purification.

PMID- 15848233
TI  - Acoustic sensor for monitoring adhesion of Neuro-2A cells in real-time.
AB  - Neuronal adhesion plays a fundamental role in growth, migration, regeneration and
      plasticity of neurons. However, current methods for studying neuronal adhesion
      cannot monitor this phenomenon quantitatively in real-time. In this work, we
      demonstrate the use of an acoustic sensor to measure adhesion of neuro-blastoma
      cells (Neuro-2A) in real-time. An acoustic sensor consisting of a quartz crystal
      sandwiched between gold electrodes was placed in a flow cell and filled with 600
      microl of phosphate buffered saline (PBS). Two sets of in vitro experiments were
      performed using sensors that had uncoated gold electrodes and sensors that were
      coated with a known neuronal adhesion promoter (poly-l-lysine or PLL). The
      instantaneous resonant frequency and the equivalent motional resistance of the
      acoustic sensor were monitored every second. Cell Tracker was used to confirm
      neuronal adhesion to the surface. Addition of 10 microl of media and Neuro-2A
      cells into the above set-up elicited exponential changes in the resonant
      frequency and motional resistance of the quartz crystal with time to reach steady
      state in the range of 2-11 h. The steady-state change in resonant frequency in
      response to addition of neurons was linearly related to the number of Neuro-2A
      cells added (R2=0.94). Acoustic sensors coated with the adhesion promoter, PLL
      showed a much higher change in resonant frequency for approximately the same
      number of neurons. We conclude that the acoustic sensor has sufficient
      sensitivity to monitor neuronal adhesion in real-time. This has potential
      applications in the study of mechanisms of neuron-substrate interactions and the
      effect of molecular modulators in the extra cellular matrix.

PMID- 15848234
TI  - Verification of somatic CAG repeat expansion by pre-PCR fractionation.
AB  - The inheritance of a long CAG repeat causes several late onset neurological
      disorders including Huntington's disease (HD). Longer CAG repeats correlate with
      earlier onset of HD suggesting an increased toxicity for the products of long
      repeat alleles. PCR based data has been used to show that HD CAG repeat expansion
      beyond the inherited length occurs in affected tissues indicating a possible role
      for somatic instability in the disease process. PCR, however, is prone to
      artifacts resulting from expansion of repeat sequences during amplification. We
      describe a method to distinguish between CAG repeat expansions that exist in vivo
      and those that potentially occur during PCR. The method involves size
      fractionation of genomic restriction fragments containing the expanded repeats
      followed by PCR amplification. The application of this method confirms the
      presence of somatic expansions in the brains of a knock-in mouse model of HD.

PMID- 15848235
TI  - Unsupervised clustering algorithm for N-dimensional data.
AB  - Cluster analysis is an important tool for classifying data. Established
      techniques include k-means and k-median cluster analysis. However, these methods
      require the user to provide a priori estimations of the number of clusters and
      their approximate location in the parameter space. Often these estimations can be
      made based on some prior understanding about the nature of the data.
      Alternatively, the user makes these estimations based on visualization of the
      data. However, the latter is problematic in data sets with large numbers of
      dimensions. Presented here is an algorithm that can automatically provide these
      estimates without human intervention based on the inherent structure of the data
      set. The number of dimensions does not limit it.

PMID- 15848236
TI  - Development of a simultaneous PET/microdialysis method to identify the optimal
      dose of 11C-raclopride for small animal imaging.
AB  - In the field of small animal positron emission tomography (PET), the assumptions
      underlying human and primate kinetic models may not be sustained in rodents. That
      is, the threshold dose at which a pharmacologic response occurs may be lower in
      small animals. In order to define this relationship, we combined microPET imaging
      using 11C-raclopride with microdialysis measures of extracellular fluid (ECF)
      dopamine (DA). In addition, we performed a series of studies in which a known
      mass of raclopride was microinfused into one striatum prior to a high specific
      activity (SA) systemic injection of 11C-raclopride. This single-injection
      approach provided a high and low SA region of radiotracer binding in the same
      animal during the same scanning session. Our data demonstrate that the binding
      potential (BP) declines above 3.5 pmol/ml (0.35 microg), with an ED50 of 8.55+/
      5.62 pmol/ml. These data also provide evidence that BP may be compromised by
      masses of raclopride below 2.0 pmol/ml (0.326 microg). Increases in ECF DA were
      produced by mass doses of raclopride over 3.9 pmol/ml (0.329 microg) with an ED50
      of 8.53+/-2.48 pmol/ml. Taken together, it appears that an optimal range of
      raclopride mass exists between 2.0 and 3.5 pmol/ml, around which the measured BP
      can be compromised by system sensitivity, endogenous DA, or excessive competition
      with unlabeled compound.

PMID- 15848238
TI  - Quantifying drug-induced dyskinesias in the arms using digitised spiral-drawing
      tasks.
AB  - In this study, we quantify the severity of drug-induced dyskinesias in the arms
      of Parkinson's disease (PD) patients using digitised spiral-drawing tasks. Two
      spiral drawings, namely a circular and a square spiral, are designed to,
      respectively, represent the continuous and discrete arm motions, and the size of
      the spiral is decided so that both the distal and proximal arm joints are
      involved. Fifteen PD patients, average disease duration 14.4+/-7.4 years, were
      assessed 30 min after a levodopa challenge whilst performing circular and square
      spiral-drawing tasks. The velocity of drawing movements was computed and the
      amplitude of the involuntary dyskinetic movements was measured as the standard
      deviation of the drawing velocity (SD-DV). The mean amplitude of dyskinetic
      movements was compared between arms and tasks and was correlated with clinical
      measures including the Bain dyskinesia scale and the total unified Parkinson's
      disease rating scale (UPDRS) score. The results showed that there was no
      statistically significant difference in the amplitude of dyskinesias either
      between the arms or between the continuous (circular) and discrete (square)
      spiral drawings in this group of PD patients, but interestingly the interaction
      between arm and drawing pattern was significant. Significant correlations were
      found between the magnitude of dyskinesia measured from the spiral-drawing tasks
      and both the 'on' or 'off' UPDRS and also the Bain dyskinesia scale. We conclude
      that the drawing tasks may be used to provide an objective method of quantifying
      the severity of drug-induced dyskinesias in the arm in PD patients.

PMID- 15848237
TI  - Histological, behavioural and neurochemical evaluation of medial forebrain bundle
      and striatal 6-OHDA lesions as rat models of Parkinson's disease.
AB  - We compared the effect of an injection of 6-hydroxydopamine (6-OHDA) into the
      medial forebrain bundle (MFB) and into the striatum on different parameters for
      evaluation of motor dysfunction and dopamine denervation in rats, as a function
      of time. A combination of behavioural, neurochemical and histological techniques
      was employed. Amphetamine-induced rotation is shown to provide a first rough
      estimation of motor impairment. Indeed, the number of rotations observed after
      amphetamine administration can distinguish between a partial and a near complete
      (>90%) denervation in the substantia nigra. However, lesion sizes of 50-80%
      resulted in similar rotational behaviour. Similarly, the elevated body swing test
      (EBST) can determine severe lesions, but is not sensitive enough in the partial
      model. In both models, determination of the dopamine tissue content with HPLC is
      a more precise measure of striatal dopamine innervation than striatal TH
      immunostaining. The number of cells estimated by TH- and Nissl-staining
      correlated well in the striatal model, but there was a discrepancy between both
      measures in the MFB-lesioned animals. Therefore, additional Nissl-staining is
      necessary for better estimation of the size of the lesion at the level of the
      substantia nigra or ventral tegmental area in the severely lesioned animals. The
      MFB lesion model mimics end-stage Parkinson's disease. The striatal injection of
      6-OHDA described here cannot be considered a progressive model, since there was
      no change in the number of TH-immunoreactive cells in the substantia nigra up to
      8 weeks post-lesioning. However, the partial denervation renders its quite
      suitable for mimicking early stage Parkinson's disease, and is thus suitable for
      testing possible neuroprotective and neurotrophic drugs.

PMID- 15848239
TI  - Spectral representation--analyzing single-unit activity in extracellularly
      recorded neuronal data without spike sorting.
AB  - One step in the conventional analysis of extracellularly recorded neuronal data
      is spike sorting, which separates electrical signal into action potentials from
      different neurons. Because spike sorting involves human judgment, it can be
      subjective and time intensive, particularly for large sets of neurons. Here we
      propose a simple, automated way to construct alternative representations of
      neuronal activity, called spectral representation (SR). In this approach,
      neuronal spikes are mapped to a discrete space of spike waveform features and
      time. Spectral representation enables us to find single-unit stimulus-related
      changes in neuronal activity without spike sorting. We tested the ability of this
      method to predict stimuli using both simulated data and experimental data from an
      auditory mapping study in anesthetized marmoset monkeys. We find that our
      approach produces more accurate classification of stimuli than spike-sorted data
      for both simulated and experimental conditions. Furthermore, this method lends
      itself to automated analysis of extracellularly recorded neuronal ensembles.
      Additionally, we suggest ways in which these representations can be readily
      extended to assist in spike sorting and the evaluation of single-neuron peri
      stimulus time histograms.

PMID- 15848240
TI  - Determination of amino acids associated with cerebral ischaemia in rat brain
      microdialysates using narrowbore liquid chromatography and fluorescence
      detection.
AB  - Microdialysis coupled to liquid chromatography (LC) has proven to be a valuable
      in vivo sampling technique for studying neurotransmitter changes in normal and
      ischaemic brain. However, few analytical methods have described the simultaneous
      determination of amino acids, relevant in stroke research, together with the
      nitric-oxide-related compound citrulline. Therefore, we developed a gradient LC
      method for the quantitative simultaneous determination of aspartate, glutamate,
      serine, glutamine, arginine, taurine, alanine and citrulline in dialysates of rat
      brain using narrowbore LC with o-phthalaldehyde-2-mercaptoethanol pre-column
      derivatisation and fluorescence detection. The proposed method is a thoroughly
      validated, fully automated and robust LC method for the determination of amino
      acids in a wide concentration range. The method was applied for the determination
      of amino acids and the citrulline/arginine ratio in the Et-1 model for focal
      cerebral ischaemia.

PMID- 15848241
TI  - Single cell glutamate analysis in Aplysia sensory neurons.
AB  - Glutamate is the major excitatory neurotransmitter in the central nervous system.
      However, techniques and assays available for the determination and detection of
      glutamate are limited. Here we have applied an effective glutamate assay toward
      the high-throughput analysis of single neurons. Initial physiological studies and
      recent immunohistochemical data strongly suggested that mechanosensory neurons
      could use L-glutamate as a co-transmitter (in addition to sensorin) in the
      sensory-motor synapse of Aplysia californica. We have evaluated the levels of
      glutamate in these cells and compared them to other non-sensory Aplysia neurons.
      Since this is the first report of this assay in single cellular analysis, a
      series of chemical and cellular controls were also done. Based on our results, we
      were able to determine the concentration levels inside single Aplysia sensory
      neurons to be 29 mM, with significant heterogeneity between individual cells. In
      comparison to the pleural mechanosensory neurons, non-sensory abdominal neurons
      contained approximately 3 mM glutamate. These elevated levels in the sensory
      neurons confirm the earlier findings [Dale N, Kandel ER. L-glutamate may be the
      fast excitatory transmitter of Aplysia sensory neurons. Proc Natl Acad Sci USA
      1993;90:7163-7.], suggesting that glutamate plays a role as neurotransmitter in
      these cells.

PMID- 15848242
TI  - A reusable microfluidic plate with alternate-choice architecture for assessing
      growth preference in tissue culture.
AB  - We present the design of a chamber to evaluate in vitro how species and
      concentrations of soluble molecules control features of cell growth-potentially
      including cell proliferation, cell motility, process extension, and process
      termination. We have created a reusable cell culture plate that integrates a
      microfluidic media delivery network with standard cell culture environment. The
      microfluidic network delivers a stream of cell culture media with a step-like
      concentration gradient down a 50-100 microm wide microchannel called the
      presentation region. Migrating cells or growing cell processes freely choose
      between the two distinct chemical environments in the presentation region, but
      they are forced to exclusively choose either one environment or the other when
      they grow past a physical barrier acting as a decision point. Our fabrication
      technique requires little specialized equipment, and can be carried out in
      approximately 4 days per plate. We demonstrate the effectiveness of our plates as
      neurites from spiral ganglion explants preferentially grow in media containing
      neurotrophin-3 (NT-3) as opposed to media without NT-3. Our design could be used
      without modification to study dissociated cell responses to soluble growth cues,
      and for behavioral screening of small motile organisms.

PMID- 15848243
TI  - Application of a non-linear image registration algorithm to quantitative analysis
      of T2 relaxation time in transgenic mouse models of AD pathology.
AB  - Transgenic mouse models have been essential for understanding the pathogenesis of
      Alzheimer's disease (AD) including those that model the deposition process of
      beta-amyloid (Abeta). Several laboratories have focused on research related to
      the non-invasive detection of early changes in brains of transgenic mouse models
      of Alzheimer's pathology. Most of this work has been performed using regional
      image analysis of individual mouse brains and pooling the results for statistical
      assessment. Here we report the implementation of a non-linear image registration
      algorithm to register anatomical and transverse relaxation time (T2) maps
      estimated from MR images of transgenic mice. The algorithm successfully
      registered mouse brain magnetic resonance imaging (MRI) volumes and T2 maps,
      allowing reliable estimates of T2 values for different regions of interest from
      the resultant combined images. This approach significantly reduced the data
      processing and analysis time, and improved the ability to statistically
      discriminate between groups. Additionally, 3D visualization of intra-regional
      distributions of T2 of the resultant registered images provided the ability to
      detect small changes between groups that otherwise would not be possible to
      detect.

PMID- 15848244
TI  - Immunocytochemical and stereological studies of the rat vestibular nucleus:
      optimal research methods using glucocorticoid receptors as an example.
AB  - Many anatomists agree that stereological procedures for counting neurons are
      superior to simple density measurements because the latter are biased by the way
      that sections are sampled and the likelihood of selectively sampling neurons of
      particular sizes and orientations. Despite this, few stereological studies of the
      vestibular nucleus complex (VNC) have been conducted and all of the published
      immunocytochemical studies have used densitometry to quantify receptor numbers.
      One possible reason for this is the difficulty of combining stereological methods
      with immunocytochemical techniques required to label specific types of receptors.
      In this paper we detail the optimal methods for combining stereological and
      immunocytochemical techniques for the unbiased quantification of neuronal number,
      using glucocorticoid receptors as an example. We report that the cryofixation
      method is more effective than perfusion with paraformaldehyde, in order to obtain
      sections to estimate neuronal number using the Cavalieri and physical disector
      methods. Thionin proved to be the optimal counterstain for identifying both
      neurons and the boundaries of the VNC. The combination of stereological and
      immunocytochemical techniques offers an effective means to ensure accurate
      estimates of the number of neurons expressing a receptor.

PMID- 15848245
TI  - Methods for isolating extracellular action potentials and removing stimulus
      artifacts from microelectrode recordings of neurons requiring minimal operator
      intervention.
AB  - Recent successes in treating neurological disorders with electrical stimulation
      of the brain have spurred interest in studying the neuronal mechanisms by which
      such therapies work. However, microelectrode recordings can be confounded by
      stimulation artifact. Also, large microelectrode arrays now allow recording
      amounts of data that would otherwise overwhelm current analytic methods that
      depend heavily on human intervention and interpretation. A set of algorithms is
      described for automatically removing stimulus artifacts that minimize signal loss
      with minimum human involvement. Other algorithms automatically differentiate
      between the extracellular action potentials of individual neurons.

PMID- 15848246
TI  - Lipid peroxidation measurement by thiobarbituric acid assay in rat cerebellar
      slices.
AB  - Lipid peroxidation by reactive oxygen species (ROS) is known to be involved in
      the damaging mechanism of several acute and chronic brain disorders. The most
      prominent and currently used assay as an index for lipid peroxidation products is
      the thiobarbituric acid assay (TBA test). It is based on the reactivity of an end
      product of lipid peroxidation, malondialdehyde (MDA) with TBA to produce a red
      adduct. However, it is known that the MDA levels are frequently overestimated,
      that the reaction lacks specificity and mainly reflects the susceptibility of
      brain tissue to the generation and degradation of newly formed lipid
      hydroperoxides under the TBA test conditions. The present paper shows that
      artifactual lipid peroxidation by TBA test conditions can be prevented and that
      the MDA level overestimation can be minimized in cerebellar slices. This can be
      done by incubating the slices in a continuous tissue perfusion system, by adding
      butylated hydroxytoluene (BHT) to the homogenization solutions and by carrying
      out the assay anaerobically on deproteinizated supernatants of cerebellar slice
      homogenates. The present research also showed that lipid peroxidation products
      generated during incubation of the slices by hydrogen peroxide (H2O2) could be
      measured without artifactual interference by the TBA test conditions.

PMID- 15848247
TI  - A refined HPLC method to measure catecholamine-o-methyltransferase activity in
      selected brain regions.
AB  - An improved HPLC method, with fluorogenic detection, for the determination of
      catecholamine-o-methyltransferase (COMT) activity in the brain has been
      developed. A catechol compound, 3,4-dihydroxybenzoic acid (3,4DOBA), was used as
      a highly fluorogenic substrate for COMT. The meta- and para-methylated products
      formed enzymatically from the substrate, after incubation with a brain region
      homogenate, were separated and measured using HPLC with fluorescence detection.
      This described method resulted in a more definitive enzyme product quantification
      with shorter analysis time than that previously described in the literature. This
      approach was used successfully to study COMT activity in vitro from small
      discreet brain regions of individual rats.

PMID- 15848248
TI  - A container for transporting small laboratory animals for magnetic resonance
      imaging.
AB  - We have constructed a simple container, consisting of a propylene tube, a High
      Efficiency Particulate Aerosol (HEPA) filter and a rubber glove, for transporting
      small animals to magnetic resonance imaging (MRI) facilities that are located
      outside a pathogen-free environment. Results of pathogens analysis indicate that
      the container is able to prevent infection by several microorganisms. The quality
      of the MR images of mice and rats transported in, and imaged while in the
      container was satisfactory. This container can be useful for examinations that
      required the use of instruments located outside clean animal units, ensuring
      safety for both humans and animals.

PMID- 15848249
TI  - Estrogenicity of butylparaben in rainbow trout Oncorhynchus mykiss exposed via
      food and water.
AB  - The estrogenic effect of butylparaben was investigated in a rainbow trout
      Oncorhynchus mykiss test system. Butylparaben was administered orally to sexually
      immature rainbow trout every second day for up to 10 days in doses between 4 and
      74 mgkg(-1)2d(-1) and in the water at 35 and 201 microgl(-1) for 12 days. Plasma
      vitellogenin was measured before and during the exposures and the concentrations
      of butylparaben in liver and muscle were determined at the end of experiments.
      Increases in average plasma vitellogenin levels were seen at oral exposure to 9
      mg butylparaben kg(-1)2d(-1). The ED50 values for increase in vitellogenin
      synthesis were 46, 29 and 10.5 mg butylparaben kg(-1)2d(-1), respectively, at day
      3, 6 and 12. Exposure to 201 microg butylparaben l(-1) increased vitellogenin
      synthesis, but exposure to 35 microgl(-1) did not. Butylparaben showed little
      tendency to bioaccumulation in rainbow trout; less than 1 per thousand of the
      total amount of butylparaben administered orally at 51 mgkg(-1)2d(-1) over the 12
      days experimental period was retained in liver at the end of the experiment.
      After 12 days exposure to 35 and 201 microg butylparaben l(-1), plasma
      concentrations were 9 and 183 microgl(-1), respectively, and for the fish exposed
      to 201 microgl(-1) there was a positive correlation between concentrations of
      vitellogenin and butylparaben in the plasma. On the assumption that butylparaben
      removed from the water phase during water exposure were taken up into the fish,
      butylparaben uptake rates in the fish exposed to 35 and 201 microg butylparaben
      l(-1) were 13 and 78 mgkg(-1)day(-1), respectively.

PMID- 15848250
TI  - Aqueous exposure to Aroclor 1254 modulates the mitogenic response of Atlantic
      salmon anterior kidney T-cells: indications of short- and long-term
      immunomodulation.
AB  - Polychlorinated biphenyls (PCBs) exist as persistent organic pollutants in
      numerous river systems in the United States. Unfortunately, some of these rivers
      are sites of active Atlantic salmon restoration programs, and polychlorinated
      biphenyls have been implicated as ancillary factors contributing to failed salmon
      restoration. Here, we investigate the immediate and chronic effects of
      intermediate duration aqueous PCB exposure (1 or 10 microgL-1 Aroclor 1254) on
      the mitogen-stimulated lymphoproliferative response of Atlantic salmon anterior
      kidney leukocytes (AKLs). A short-term study was designed to examine
      immunomodulation in Atlantic salmon smolts immediately following 21 days of
      aqueous exposure, while a long-term study evaluated chronic impacts in the
      mitogen response in parr 15 months post-exposure as larvae. The proliferative
      response of AKLs to the mitogens concanavalin A (CON A), phytohemaglutinnin-P
      (PHA-P), pokeweed mitogen (PWM), and lipopolysaccharide were used as an indice of
      immunomodulation. The proliferative response to the T-cell mitogens CON A and PHA
      P was significantly increased in the 10 microgL-1 group (n=10; P=0.043 and 0.002,
      respectively) immediately following exposure of smolts. Additionally, The PHA-P
      response was significantly increased in the 1 microgL-1 exposure group (n=10,
      P=0.036). In fish treated as larvae and tested 15 months later, the PHA-P
      sensitive populations exhibited elevated proliferation in the 1 and 10 microgL-1
      groups (n=12, P<0.04) relative to the vehicle control while the PWM response was
      significantly increased (n=12, P=0.036) only in the 10 microgL-1 treated groups.
      These results demonstrate an immunomodulatory effect of PCBs on T-cell mitogen
      sensitive populations of lymphocytes in Atlantic salmon as well as long-term
      immunomodulation in PHA-P and PWM sensitive populations.

PMID- 15848251
TI  - The selection of a model microalgal species as biomaterial for a novel aquatic
      phytotoxicity assay.
AB  - A phytotoxicity assay based on the ToxY-PAM dual-channel yield analyser has been
      developed and successfully incorporated into field assessments for the detection
      of phytotoxicants in water. As a means of further exploring the scope of the
      assay application and of selecting a model biomaterial to complement the
      instrument design, nine algal species were exposed to four chemical substances
      deemed of priority for water quality monitoring purposes (chlorpyrifos, copper,
      diuron and nonylphenol ethoxylate). Inter-species differences in sensitivity to
      the four toxicants varied by a factor of 1.9-100. Measurements of photosystem-II
      quantum yield using these nine single-celled microalgae as biomaterial
      corroborated previous studies which have shown that the ToxY-PAM dual-channel
      yield analyser is a highly sensitive method for the detection of PS-II impacting
      herbicides. Besides Phaeodactylum tricornutum, the previously applied
      biomaterial, three other species consistently performed well (Nitzschia
      closterium, Chlorella vulgaris and Dunaliella tertiolecta) and will be used in
      further test optimisation experiments. In addition to sensitivity, response time
      was evaluated and revealed a high degree of variation between species and
      toxicants. While most species displayed relatively weak and slow responses to
      copper, C. vulgaris demonstrated an IC10 of 51 microgL-1, with maximum response
      measured within 25 minutes and inhibition being accompanied by a large decrease
      in fluorescence yield. The potential for this C. vulgaris-based bioassay to be
      used for the detection of copper is discussed. There was no evidence that the
      standard ToxY-PAM protocol, using these unicellular algae species, could be used
      for the detection of chlorpyrifos or nonylphenol ethoxylate at environmentally
      relevant levels.

PMID- 15848252
TI  - Impact of bioavailability on the correlation between in vitro cytotoxic and in
      vivo acute fish toxic concentrations of chemicals.
AB  - The lower sensitivity of in vitro cytotoxicity assays currently restricts their
      use as alternative to the fish acute toxicity assays for hazard assessment of
      chemicals in the aquatic environment. In vitro cytotoxic potencies mostly refer
      to nominal concentrations. The main objective of the present study was to
      investigate, whether a reduced availability of chemicals in vitro can account for
      the lower sensitivity of in vitro toxicity test systems. For this purpose, the
      bioavailable free fractions of the nominal cytotoxic concentrations (EC50) of
      chemicals determined with a cytotoxicity test system using Balb/c 3T3 cells and
      the corresponding free cytotoxic concentrations (ECu50) were calculated. The
      algorithm applied is based on a previously developed simple equilibrium
      distribution model for chemicals in cell cultures with serum-supplemented culture
      media. This model considers the distribution of chemicals between water, lipids
      and serum albumin. The algorithm requires the relative lipid volume of the test
      system, the octanol-water partition coefficient (K(ow)) and the in vitro albumin
      bound fraction of the chemicals. The latter was determined from EC50-measurements
      in the presence of different albumin concentrations with the Balb/c 3T3 test
      system. Organic chemicals covering a wide range of cytotoxic potency (EC50: 0.16
      527000 microM) and lipophilicity (logK(ow): -5.0-6.96) were selected, for which
      fish acute toxicity data (LC50-values) from at least one of the three fish
      species, medaka, rainbow trout and fathead minnow, respectively, were available.
      The availability of several chemicals was shown to be extensively reduced either
      by partitioning into lipids or by serum albumin binding, or due to both
      mechanisms. Reduction of bioavailability became more important with increasing
      cytotoxic potency. The sensitivity of the Balb/c 3T3 cytotoxicity assay and the
      correspondence between in vivo and in vitro toxic potencies were increased when
      the free cytotoxic concentrations instead of the nominal cytotoxic concentrations
      were used as measure of cytotoxic potency. The few remaining prominent
      differences between cytotoxic and acute toxic concentrations can be explained by
      a more specific mechanism of acute toxic action than basal cytotoxicity. It is
      concluded that the frequently observed low sensitivity of in vitro cytotoxicity
      test systems, compared to fish acute toxicity assays, at least in part, can be
      explained by differences in the availability of chemicals in vitro and in vivo.
      Moreover, neglecting these differences systematically causes a bias of the
      correlation between in vivo and in vitro toxic potencies of chemicals. Taking
      them into account, however, increases the predictivity of the in vitro assays.

PMID- 15848253
TI  - Silver accumulation in Daphnia magna in the presence of reactive sulfide.
AB  - Previously, we demonstrated a higher silver body burden when Daphnia magna were
      exposed to silver in the presence of environmentally relevant concentrations (25
      nM) of reactive sulfide, but the explanation was unclear. In the present study,
      D. magna were exposed to AgNO3 (0.93 microg Ag/L=8.6 nM as a mixture of cold Ag
      and (110m)Ag) in synthetic water in either the presence or absence of 25 nM
      sulfide as zinc sulfide clusters. After 1-h exposure, daphnids were transferred
      to clean water for up to 5-h depuration. At different times of Ag exposure and
      depuration, daphnids were randomly sampled for whole body silver burden. Also,
      after 1 h, daphnids were sampled for silver accumulation in "gills" (small organs
      on the thoracic appendages), digestive tract, and carcass. Other groups were
      exposed to the same silver and sulfide concentrations for 1 h and then sampled
      for whole-body autoradiography. Silver body burden was about two-fold higher in
      the presence of sulfide. A two-fold increase in silver burden in "gills" and
      digestive tract, but not in carcass, was also observed in the presence of
      sulfide. Absolute differences due to sulfide were greatest in digestive tract and
      explained most of the difference in whole body burden. Transfer to clean water
      caused a significant drop in silver concentration in whole body and all
      compartments to similar levels in the two groups after 5-h depuration. These
      results indicate that the higher silver body burden observed in the presence of
      sulfide is mainly due to sulfide-bound silver in the digestive tract of the
      daphnids. This conclusion is supported by autoradiography, which showed a high
      concentration of silver in the digestive tract of daphnids exposed to Ag/sulfide.

PMID- 15848254
TI  - Hydrogen peroxide is not the cause of fish kills associated with Chattonella
      marina: cytological and physiological evidence.
AB  - Chattonella marina, a harmful algal bloom (HAB) causative species, was used to
      study the mortality, physiology, and pathology of a marine stenohaline fish,
      goldlined seabream exposed to the toxic alga. The median lethal time (LT50) was 3
      h upon exposure to 8000 cells/ml of C. marina. Significant induction of
      filamental chloride cells (CCs) [i.e. increases in CC fractional area and in the
      volume density of CCs], concomitant with significant reduction of blood
      osmolality, were found in C. marina treated fish. To verify whether the toxicity
      of C. marina was mediated through oxidative stress, a hydrogen peroxide exposure
      experiment was carried out and the toxicity as well as cytological and
      physiological changes were compared with the C. marina treatment. Hydrogen
      peroxide at a concentration of 500 microM H2O2, (i.e. 25 times higher than that
      produced by 8000 cells/ml of C. marina (20 microM H2O2)) was unable to induce
      similar CC alterations and osmoregulatory impairment in fish as observed in the
      C. marina treatment. Non-specific membrane damage such as severe loss of
      microvilli projections on the CC apical opening and rupture of epithelial
      membranes in the lamellae were observed. The LT50 was 6 h, two times longer than
      that with 8000 cells/ml of C. marina. Based on the cytological and physiological
      evidence and toxicity data, the mechanism by which C. marina kills fish appears
      to be very different from that caused by H2O2/ROS. Osmoregulatory distress is the
      major cause of fish death upon exposure to C. marina.

PMID- 15848255
TI  - Properties and regional expression of a CYP3A-like protein in channel catfish
      intestine.
AB  - Biotransformation in the intestine may influence the bioavailability and toxicity
      of ingested xenobiotics. The objective of this study was to examine the
      expression and catalytic properties of a constitutive cytochrome P450 (CYP) 3A
      like protein along the intestine of channel catfish, Ictalurus punctatus. Fish
      were maintained on commercial chow or nutritionally complete semi-purified diets.
      Polyclonal antibodies generated against rainbow trout CYP3A proteins reacted
      strongly with catfish washed intestinal microsomes on Western blots showing a
      major protein band with MW of 59 kDa. In catfish maintained on a standard chow
      diet, the expression of this protein was higher in the proximal segment (0.101 +/
      0.031 units/mg protein, mean +/- S.D., n = 4) than in the distal part (0.032 +/-
      0.023 units/mg protein). Microsomal testosterone 6beta-hydroxylation activity was
      monitored as the catalytic indicator of CYP3A, and was higher in proximal than
      distal catfish intestine (263 +/- 80.3 and 88.6 +/- 15.6 pmol/min/mg protein for
      proximal and distal, respectively, mean +/- S.D., n = 4). CYP3A protein levels
      and testosterone 6beta-hydroxylation activities were lower in microsomes from the
      proximal segment of intestine from catfish maintained on a semi-purified diet,
      compared with commercial chow, but again the proximal intestine had higher CYP3A
      and 6beta-hydroxylase activities than distal intestine. Testosterone 6beta
      hydroxylase activities in all samples correlated with the CYP3A protein levels,
      r2 = 0.8. Testosterone 6beta-hydroxylation was inhibited by specific CYP3A
      inhibitors, ketoconazole (IC50 = 0.02 microM) and erythromycin (IC50 = 41
      microM), as well as general CYP inhibitors, metyrapone (IC50 = 2.8 microM) and
      SKF-525A (IC50 = 25 microM). There was evidence for the involvement of CYP3A in
      the mono-oxygenation of benzo(a)pyrene and of (-)-benzo(a)pyrene-7,8-dihydrodiol
      in intestinal microsomes from catfish maintained on the semi-purified diet. Mono
      oxygenation of both substrates was increased in a concentration-dependent manner
      by in vitro addition of alpha-naphthoflavone. Benzo(a)pyrene hydroxylase
      activities were higher in proximal than in distal intestine; 3.72 +/- 0.77
      pmol/min/mg protein, mean +/- S.D., n = 5 and 1.45 +/- 0.42 in these respective
      segments. The results of this study strongly suggest that CYP3A is important in
      the first pass metabolism of dietary xenobiotics in untreated fish.

PMID- 15848256
TI  - Impact of pesticide application on zooplankton communities with different
      densities of invertebrate predators: an experimental analysis using small-scale
      mesocosms.
AB  - We assessed the responses of zooplankton communities with different population
      densities of an invertebrate predator, Mesocyclops pehpeiensis, to insecticide
      (carbaryl, 0.5 mgL(-1)) in small-scale mesocosm tanks (20 L). Cladocerans were
      eliminated by carbaryl application at both high and low predator densities. The
      density of rotifers increased after the elimination of the cladocerans by
      carbaryl application at low-predator density but not at high-predator density.
      Carbaryl application increased the relative importance of predatory interactions
      in the zooplankton community. The results suggest that predator abundance can
      affect the response of a zooplankton community to carbaryl application through
      predation on surviving zooplankton.

PMID- 15848257
TI  - Plasma concentrations of estradiol and testosterone, gonadal aromatase activity
      and ultrastructure of the testis in Xenopus laevis exposed to estradiol or
      atrazine.
AB  - The ultrastructure of testicular cells of adult male African clawed frogs
      (Xenopus laevis) exposed to either estradiol (0.1 microg/L) or 2-chloro-4
      ethylamino-6-isopropyl-amino-s-triazine (atrazine; 10 or 100 microg/L) was
      examined by electron microscopy and compared to plasma concentrations of the
      steroid hormones, testosterone (T) and estradiol (E2), testicular aromatase
      activity and gonad growth expressed as the gonado-somatic index (GSI). Exposure
      to E2 caused significant changes both at the sub-cellular and biochemical levels.
      Exposure to E2 resulted in significantly fewer sperm cells, inhibition of meiotic
      division of germ cells, more lipid droplets that are storage compartments for the
      sex steroid hormone precursor cholesterol, and lesser plasma T concentrations.
      Although not statistically significant, frogs exposed to E2 had slightly smaller
      GSI values. These results may be indicative of an inhibition of gonad growth and
      disrupted germ cell development by E2. Concentrations of E2 in plasma were
      greater in frogs exposed to E2 in water. Exposure to neither concentration of
      atrazine caused effects on germ cell development, testicular aromatase activity
      or plasma hormone concentrations. These results suggest that atrazine does not
      affect testicular function. In contrast, exposure of male X. laevis to E2 led to
      sub-cellular events that are indicative of disruption of testicular development,
      and demasculinization processes (decrease of androgen hormone titers). These
      results indicate that atrazine does not cause responses that are similar to those
      caused by exposure to E2.

PMID- 15848258
TI  - [Home postural evaluation in the elderly: comparison between fallers and non
      fallers].
AB  - OBJECTIVES: To determine the main clinical and posturographic factors correlated
      with falls in elderly individuals and to specify the role of static posturography
      in this appraisal. MATERIALS AND METHODS: The study involved 38 people living in
      an residential center who were autonomously ambulatory and had a Mini Mental Test
      score> or =24. Fallers (N = 15) had fallen within 1 month, and nonfallers (N =
      23) had not fallen for at least a year. Assessment consisted of a series of
      questions, a complete clinical appraisal, specific independently validated tests,
      and static posturographic analysis different parameters of the stabilogram with
      the eyes first open and then closed, all carried out in the center. RESULTS: From
      the clinical standpoint, spinal pathologic features and the scores on the
      Functional Reach Test were significantly different between the fallers and
      nonfallers. In static posturography, fallers' equilibrium was more precarious
      than that of nonfallers with eyes are closed: significant differences were
      observed in surface, X length and overall fast Fourier transform score. The
      comparison between results with open and closed eyes showed that the fallers had
      a pronounced tendency to retropulsion in the absence of visual participation: a
      significant difference as regards overall length, Y length, minimum Y and FFT Y
      (0.5-2 Hz). CONCLUSIONS: To complement a satisfactorily conducted clinical
      examination, static posturography allows for rapid assessment of equilibrium and
      posture in elderly patients who fall? Performed at the place where an individual
      resides, this appraisal constitutes an original and pragmatic element. As an
      evaluation strategy, it can reveal nonnegligible information within the framework
      of an appraisal of such, and thereby allows for adjustment of the rehabilitation
      or compensatory strategy.

PMID- 15848259
TI  - [Botulinum toxin injections and hypertonic upper limbs. Which functional
      results?].
AB  - OBJECTIVES: To assess the efficacy of botulinum toxin injections for hypertonic
      upper limbs in patients with residual motricity that allows a functional use of
      the hand. METHODS: Patients were seen between February 2000 and November 2002,
      before and after botulinum toxin injections for hypertonic upper limbs due to
      upper motor neuron syndrome. All patients had voluntary motricity in fingers and
      wrist extensors. Impairment (range of motion, spasticity [Ashworth's scale]),
      pain (10 centimeters visual analog scale) prehension (400-point measure) and
      patients' satisfaction were recorded. Two or three functional goals were
      predefined. Patients were injected after locating the target area with
      neurostimulation. The aim of the injections was functional improvement. RESULTS:
      Eight patients were included. After injections, mean pain score decreased by 3.4
      points; mean spasticity decreased by 1.0; and prehension improved, especially for
      bimanual functions. Three-quarters of the functional goals were reached. Optimal
      efficacy required repeated injections, with modification of muscle targets and
      doses. CONCLUSION: Botulinum toxin injection is efficient for impairment, pain
      and prehension in hypertonic upper limbs, even if the hypertonic hand is still
      the "nondominant" hand. Motricity in antagonist muscles is essential for
      functional improvement, and the assessment must include bimanual tasks. Intrinsic
      as well as extrinsic muscles must be injected and a neurostimulator used for
      forearm muscles. Comparative studies are required to define more clearly the
      place of this treatment among medical and surgical treatments of spasticity.

PMID- 15848260
TI  - [Hemiplegia and a hiking tour of Mont Blanc: from hope to reality].
AB  - INTRODUCTION: At the end of an endurance training program for stroke patients
      with hemiplegia, we offered a hiking tour around the Mont Blanc Pedestrian Tour.
      We found no publication describing a similar experience and no scientific data in
      the literature to determine the physiological characteristics required for this
      performance, particularly regarding cardiac and vascular capacities, level of
      impairment, and functional abilities. OBJECTIVE: To complete a part of the Mont
      Blanc Pedestrian Tour over six days, with a group of adults with hemiparesis and
      aphasia due to stroke. POPULATION: Seven of 20 subjects with right hemiparesis
      and aphasia were selected on the basis of results of physiological tests, after
      an endurance training program and two tests hikes at medium altitude. Mean age
      was 51.71 +/- 7.13 years, mean VO(2max) 19.76 +/- 3.46 ml.g(-1).mm(-1), mean
      P(max) 90 +/- 22.68 and mean walking speed 3.60 +/- 1.30 km/hour. ORGANIZATION:
      Organization involved setting up the itinerary, recruiting accompanying personnel
      (9 people), and arranging security. No specific adaptations for accessibility
      were available, and no specific equipment was used, except for standard walking
      sticks. RESULTS: During this pedestrian tour, the subjects demonstrated strong
      motivation, as well as exceptional physical and functional performance, despite
      significant changes in elevation (up to 1500 m per day) and long walking times
      (from 5 to 9 hours per day). DISCUSSION: This experience has enriched our
      reflection about the medical, functional, and psychological conditions required
      for this type of physical effort, both from patients and accompanying personnel.
      In the absence of reports on similar experiences with this patient population, we
      thought it interesting, six months after this challenge, to present our
      observations as well as the patients' point of view. This may encourage other
      rehabilitation teams to offer intensive walking activities for stroke patients.

PMID- 15848261
TI  - [Postural biofeedback and locomotion reeducation in stroke patients].
AB  - AIMS: To compare, in post-acute hemiparetic patients, gait improvement after
      conventional physical therapy alone or with a specialised balance retraining
      program. PATIENTS: Twenty-six patients within 3 months of onset of stroke were
      randomised to receive physical therapy (control group) or therapy and retraining
      (experimental group), most of the patients in both groups with left hemiplegia.
      The experimental group was significantly older than the control group. METHOD:
      Thirteen patients received early conventional therapy, and 13 received therapy
      combined with standing balance training by biofeedback (BPM Monitor). Clinical
      measures were collected at entry (J0), once when subjects began to walk (JM) and
      30 days later (JM + 30). Gait spatiotemporal parameters were collected by use of
      the Vicon system at JM and JM + 30. RESULTS: Whatever the method of
      rehabilitation, the clinical scores improved significantly between J0 and JM +
      30, except for spasticity. The time between stroke and the beginning of walking
      was not significantly different between both groups. Gait velocity increased
      significantly between JM and JM + 30 in both groups, with no difference between
      groups. The walking pattern was improved for both groups, with a significant
      increase of the duration of the paretic limb single stance. The experimental
      group significantly improved the duration of the reception double stance on the
      paretic limb between JM and JM + 30 compared with the control group (P = 0.03).
      CONCLUSION: Both groups demonstrated improvement in the rehabilitation unit. The
      benefits of visual biofeedback by forceplate system training suggest particular
      improvement of anticipation equilibrium with conventional therapy.

PMID- 15848262
TI  - [Reeducation of gait in stroke patients: is there something new?].

PMID- 15848263
TI  - [Towards a better understanding and quantitative assessment of pushing, a
      postural behaviour caused by some strokes].
AB  - INTRODUCTION: Postural control aims to build up and align the body orientation
      (posture) and stabilize body segments. The existence of two separate mechanisms,
      one for the control of body orientation with respect to gravity and one for its
      stabilisation, is an emerging concept that allows a better understanding of
      postural disorders, including pushing, after stroke. Objectives. - Literature
      review concerning pushing, one of the most puzzling postural behaviours after
      stroke. METHODS: Critical review of papers indexed in Medline and book chapters
      dealing with pushing. RESULTS: There is no agreement about the definition of
      pushing: some authors consider that pushers push himself toward the paretic side
      using the healthy arm or leg; others consider that pushers lean (list) toward the
      side opposite the lesion and resist any attempt to become more upright.
      Surprisingly, the push itself has never been measured. Some ordinal scales have
      been recently proposed, but their psychometric properties have not been analysed.
      These methodological insufficiencies explain in part the disagreements about
      frequency (from 5% to 50% of patients with stroke) and cause(s) of pushing.
      CONCLUSION: Pushing may be the most dramatic clinical manifestations of an
      extreme bias in the construction of the biological vertical. We argue for a
      better assessment of vertical perception/representation after stroke involving
      the three modalities of the biological (subjective) vertical: the visual
      vertical, the haptic or tactile vertical, and especially the postural vertical.

PMID- 15848264
TI  - [Value of intensive rehabilitation in fixed dropped head syndrome].
AB  - OBJECTIVES: To point out the diagnostic and etiologic context of neck extensor
      weakness and to consider orthopedic and rehabilitation treatment of dropped head
      syndrome. METHODS: We report a case of a 68-year-old hospitalized woman with
      atypical and serious idiopathic neck extensor weakness who was treated by
      orthopedic measurements and intensive rehabilitation. RESULTS: Our patient had
      progressive neck extensor weakness and total inflection of the cervico-cephalic
      axis over two years. Fixed and permanent contact of the chin and the sternum
      severely affected her ability to eat, and mandibular and sternal pressure ulcers
      developed. Cervical spine radiography revealed degenerative lesions. Other
      clinical and biological parameters were normal. Atypical idiopathic head drop was
      diagnosed because of painful and fixed head position. Rehabilitation consisted of
      cervical traction with a halo apparatus during eight weeks and an exercise
      programme based on cervical proprioception and muscular work. Orthopedic
      management consisted of cervical collar immobilization after cutaneous
      cicatrization. After ten weeks of treatment, the patient was able to raise her
      head and maintain it horizontally. Two years later, clinical results were stable.
      DISCUSSION: Neck extensor weakness may be the presenting feature of several
      neuromuscular disorders. Generally, idiopathic dropped head syndrome appears to
      be the most likely diagnosis in patients with isolated neck extensor involvement.
      For our patient, clinical findings and cervical computed tomography showed
      important muscular weakness. However, painful passive extension and progressive
      stiffness of the neck do not represent the typical clinical course of idiopathic
      head drop. Neither degenerative lesions of the cervical spine nor other joint
      diseases can cause head drop. This case may result from the combined effects of
      idiopathic dropped head syndrome and cervical arthrosis. Orthopedic treatment and
      intensive rehabilitation had spectacular effects. Clinical management of head
      drop syndrome should always consist of orthopedic and rehabilitation treatment.

PMID- 15848265
TI  - Classification of EEG signals using neural network and logistic regression.
AB  - Epileptic seizures are manifestations of epilepsy. Careful analyses of the
      electroencephalograph (EEG) records can provide valuable insight and improved
      understanding of the mechanisms causing epileptic disorders. The detection of
      epileptiform discharges in the EEG is an important component in the diagnosis of
      epilepsy. As EEG signals are non-stationary, the conventional method of frequency
      analysis is not highly successful in diagnostic classification. This paper deals
      with a novel method of analysis of EEG signals using wavelet transform and
      classification using artificial neural network (ANN) and logistic regression
      (LR). Wavelet transform is particularly effective for representing various
      aspects of non-stationary signals such as trends, discontinuities and repeated
      patterns where other signal processing approaches fail or are not as effective.
      Through wavelet decomposition of the EEG records, transient features are
      accurately captured and localized in both time and frequency context. In
      epileptic seizure classification we used lifting-based discrete wavelet transform
      (LBDWT) as a preprocessing method to increase the computational speed. The
      proposed algorithm reduces the computational load of those algorithms that were
      based on classical wavelet transform (CWT). In this study, we introduce two
      fundamentally different approaches for designing classification models
      (classifiers) the traditional statistical method based on logistic regression and
      the emerging computationally powerful techniques based on ANN. Logistic
      regression as well as multilayer perceptron neural network (MLPNN) based
      classifiers were developed and compared in relation to their accuracy in
      classification of EEG signals. In these methods we used LBDWT coefficients of EEG
      signals as an input to classification system with two discrete outputs: epileptic
      seizure or non-epileptic seizure. By identifying features in the signal we want
      to provide an automatic system that will support a physician in the diagnosing
      process. By applying LBDWT in connection with MLPNN, we obtained novel and
      reliable classifier architecture. The comparisons between the developed
      classifiers were primarily based on analysis of the receiver operating
      characteristic (ROC) curves as well as a number of scalar performance measures
      pertaining to the classification. The MLPNN based classifier outperformed the LR
      based counterpart. Within the same group, the MLPNN based classifier was more
      accurate than the LR based classifier.

PMID- 15848266
TI  - Registration of MR and CT images of the liver: comparison of voxel similarity and
      surface based registration algorithms.
AB  - The purpose of this work was to determine the feasibility and efficacy of
      retrospective registration of MR and CT images of the liver. The open-source ITK
      Insight Software package developed by the National Library of Medicine (USA)
      contains a multi-resolution, voxel-similarity-based registration algorithm which
      we selected as our baseline registration method. For comparison we implemented a
      multi-scale surface fitting technique based on the head-and-hat algorithm.
      Registration accuracy was assessed using the mean displacement of automatically
      selected point landmarks. The ITK voxel-similarity-based registration algorithm
      performed better than the surface-based approach with mean misregistration in the
      range of 7.7-8.4 mm for CT-CT registration, 8.2 mm for MR-MR registration, and
      14.0-18.9 mm for MR-CT registration compared to mean misregistration from the
      surface-based technique in the range of 9.6-11.1 mm for CT-CT registration, 9.2
      12.4 mm for MR-MR registration, and 15.2-19.0 mm for MR-CT registration.

PMID- 15848267
TI  - On line extraction of temporal episodes from ICU high-frequency data: a visual
      support for signal interpretation.
AB  - This paper presents a method to extract on line temporal episodes from high
      frequency physiological parameters monitored in ICU, as a visual support for
      signal interpretation. Temporal episodes are expressions such as: "systolic blood
      pressure is steady at 120 mmHg from time t(0) until time t(1); it increases from
      120 to 160 mmHg from time t(1) to time t(2) ...". Three words are used to
      describe the data evolution: {steady, increasing, decreasing}. The method deals
      with noisy data and missing values. It uses a segmentation algorithm that was
      developed previously and a classification of the segments into temporal patterns.
      The results obtained on simulated data are quite satisfactory. They show that the
      method is able to detect rapid variations as well as slow trends. Episodes
      extracted from real S(p)o(2) data recorded over a period of 44 h from 10
      different adult patients are analysed. The visual representation of the temporal
      episodes is a powerful tool to help the physicians analyse in a glance the
      evolution in time of the variables monitored. It can help carer personnel to make
      quicker decisions in alarm situations.

PMID- 15848268
TI  - Correlation dimension analysis of heart rate variability in patients with dilated
      cardiomyopathy.
AB  - A correlation dimension analysis of heart rate variability (HRV) was applied to a
      group of 55 patients with dilated cardiomyopathy (DCM) and 55 healthy subjects as
      controls. The 24-h RR time series for each subject was divided into segments of
      10,000 beats to determine the correlation dimension (CD) per segment. A study of
      the influence of the time delay (lag) in the calculation of CD was performed.
      Good discrimination between both groups (p<0.005) was obtained with lag values of
      5 or greater. CD values of DCM patients (8.4+/-1.9) were significantly lower than
      CD values for controls (9.5+/-1.9). An analysis of CD values of HRV showed that
      for healthy people, CD night values (10.6+/-1.8) were significant greater than CD
      day values (9.2+/-1.9), revealing a circadian rhythm. In DCM patients, this
      circadian rhythm was lost and there were no differences between CD values in day
      (8.8+/-2.4) and night (8.9+/-2.1).

PMID- 15848269
TI  - Mapping the dimensionality, density and topology of data: the growing adaptive
      neural gas.
AB  - Self-organized maps are commonly applied for tasks of cluster analysis, vector
      quantization or interpolation. The artificial neural network model introduced in
      this paper is a hybrid model of the growing neural gas model introduced by
      Fritzke (Fritzke, in Advances in Neural Information Processing Systems 7, MIT
      Press, Cambridge MA, 1995) and the adaptive resolution clustering modification
      for self-organized maps proposed by Firenze (Firenze et al., in International
      Conference on Artificial Neural Networks, Springer-Verlag, London, 1994). The
      hybrid model is capable of mapping the distribution, dimensionality and topology
      of the input data. It has a local performance measure that enables the network to
      terminate growing in areas of the input space that is mapped by units reaching a
      performance goal. Therefore the network can accurately map clusters of data
      appearing on different scales of density. The capabilities of the algorithm are
      tested using simulated datasets with similar spatial spread but different local
      density distributions, and a simulated multivariate MR dataset of an anatomical
      human brain phantom with mild multiple sclerosis lesions. These tests demonstrate
      the advantages of the model compared to the growing neural gas algorithm when
      adaptive mapping of areas with low sample density is desirable.

PMID- 15848270
TI  - Development and applications of a software for Functional Image Registration
      (FIRE).
AB  - Image registration with anatomical modalities, such as CT and MRI, facilitates
      the anatomical identification and localization in the interpretation of nuclear
      medicine images that lack anatomical information. The implementation of
      Functional Image Registration (FIRE), an operating system (OS) and platform
      independent multimodal image registration software is reported. In order to
      register the images without an operator's interaction, several automatic
      algorithms were implemented. These include principal axes matching and
      maximization of the mutual information methods. The user interface was designed
      to support the manual registration of the images. Fused images were composed by
      overlaying one image with the other one transparently, in which the opacity of
      the overlaid image was interactively controlled. FIRE was successfully applied to
      many clinical cases for which automatic and/or manual registration was required.
      An OS and platform independent program for image registration developed in this
      study will be useful for the clinical application of image registration
      techniques.

PMID- 15848271
TI  - Estimation of linear mixed models with a mixture of distribution for the random
      effects.
AB  - The aim of this paper is to propose an algorithm to estimate linear mixed model
      when random effect distribution is a mixture of Gaussians. This heterogeneous
      linear mixed model relaxes the classical Gaussian assumption for the random
      effects and, when used for longitudinal data, can highlight distinct patterns of
      evolution. The observed likelihood is maximized using a Marquardt algorithm
      instead of the EM algorithm which is frequently used for mixture models. Indeed,
      the EM algorithm is computationally expensive and does not provide good
      convergence criteria nor direct estimates of the variance of the parameters. The
      proposed method also allows to classify subjects according to the estimated
      profiles by computing posterior probabilities of belonging to each component. The
      use of heterogeneous linear mixed model is illustrated through a study of the
      different patterns of cognitive evolution in the elderly. HETMIXLIN is a free
      Fortran90 program available on the web site: http://www.isped.u-bordeaux2.fr.

PMID- 15848272
TI  - RSURV: a function to perform relative survival analysis with S-PLUS or R.
AB  - Relative survival is a method used to estimate net survival using the expected
      mortality in the general population. This method is frequently used in cancer
      registries, more particularly with the Esteve et al. regressive proportional
      hazards model. Recently, extensions of this model have been developed to account
      for time-dependent covariate and for time-dependent hazards using B-spline
      functions. We propose a function, RSurv, to take into account these extensions.
      Written in the R/S language this function has the same structure of the standard
      Cox function coxph of R and S-PLUS software with the goal to homogenise survival
      functions and to take advantages of the power of R and S-PLUS software. We also
      propose a function, plot.RSurv, for plotting relative survival curves and time
      dependent hazards ratio. The usage of these functions is exemplified by a study
      of a breast cancer hospital-based data set.

PMID- 15848273
TI  - Pathogenic significance of alpha-N-acetylgalactosaminidase activity found in the
      hemagglutinin of influenza virus.
AB  - Serum vitamin D3-binding protein (Gc protein) is the precursor for the principal
      macrophage activating factor (MAF). The precursor activity of serum Gc protein
      was reduced in all influenza virus-infected patients. These patient sera
      contained alpha-N-acetylgalactosaminidase (Nagalase) that deglycosylates Gc
      protein. Deglycosylated Gc protein cannot be converted to MAF, thus it loses the
      MAF precursor activity, leading to immunosuppression. An influenza virus stock
      contained a large amount of Nagalase activity. A sucrose gradient centrifugation
      analysis of the virus stock showed that the profile of Nagalase activity
      corresponds to that of hemagglutinating activity. When these gradient fractions
      were treated with 0.01% trypsin for 30 min, the Nagalase activity of each
      fraction increased significantly, suggesting that the Nagalase activity resides
      on an outer envelope protein of the influenza virion and is enhanced by the
      proteolytic process. After disruption of influenza virions with sodium
      deoxycholate, fractionation of the envelope proteins with mannose-specific lectin
      affinity column along with electrophoretic analysis of the Nagalase peak fraction
      revealed that Nagalase is the intrinsic component of the hemagglutinin (HA).
      Cloned HA protein exhibited Nagalase activity only if treated with trypsin. Since
      both fusion capacity and Nagalase activity of HA protein are expressed by
      proteolytic cleavage, Nagalase activity appears to be an enzymatic basis for the
      fusion process. Thus, Nagalase plays dual roles in regulating both infectivity
      and immunosuppression.

PMID- 15848274
TI  - Activity of vaccinia virus-neutralizing antibody in the sera of smallpox
      vaccinees.
AB  - Individuals vaccinated against smallpox maintain substantial antiviral antibody
      responses for many years after vaccination. In this study, we examined the
      ability of antiviral antibodies from 104 unique serum samples to neutralize the
      two infectious forms of vaccinia virus, intracellular mature virus (IMV) and
      extracellular enveloped virus (EEV). While we found direct correlations between
      antiviral antibody titers and the ability to neutralize IMV and EEV, correlation
      with EEV neutralization was weaker. To determine factors that may influence more
      varied EEV neutralization within a vaccinated population, we asked the following
      questions. (1) Does vaccinia virus-neutralizing ability remain constant over
      time? (2) Do multiple vaccinations boost IMV and EEV neutralization activity? We
      found that serum from vaccinated individuals retained ability to neutralize EEV
      for a relatively long time, but there was a significant drop in EEV
      neutralization ability in the third decade after vaccination. While all vaccinees
      maintained some ability to neutralize IMV, a number of individuals lost the
      capacity to neutralize EEV. Interestingly, the ability to neutralize either virus
      form was not altered by the number of vaccinations received. Since it is likely
      that neutralizing antibodies against both IMV and EEV are required for maximal
      protective immunity, a loss of anti-EEV-neutralizing ability may warrant the
      revaccination of individuals who have been vaccinated >20 years ago, should
      widespread pre-event smallpox vaccination be instituted.

PMID- 15848275
TI  - Differential antibody responses to Plasmodium falciparum
      glycosylphosphatidylinositol anchors in patients with cerebral and mild malaria.
AB  - Glycosylphosphatidylinositol (GPI) membrane anchors of Plasmodium falciparum
      surface proteins are thought to be important factors contributing to malaria
      pathogenesis, and anti-GPI antibodies have been suggested to provide protection
      by neutralizing the toxic activity of GPIs. In this study, IgG responses against
      P. falciparum GPIs and a baculovirus recombinant MSP1p19 antigen were evaluated
      in two distinct groups of 70 patients each, who were hospitalized with malaria.
      Anti-GPI IgGs were significantly lower in patients hospitalized with confirmed
      cerebral malaria compared to those with mild malaria (P < 0.01) but did not
      discriminate for fatal outcome. In contrast, a specific marker of the anti
      parasite immunity, as monitored by the anti-MSP1p19 IgG response, was similar in
      both cerebral and mild malaria individuals, although it was significantly lower
      in a subgroup with fatal outcomes. These results are consistent with a potential
      anti-toxin role for anti-GPI antibodies associated with protection against
      cerebral malaria.

PMID- 15848276
TI  - Identification of multiple HLA-A*0201-restricted cruzipain and FL-160 CD8+
      epitopes recognized by T cells from chronically Trypanosoma cruzi-infected
      patients.
AB  - Chronic Chagas disease occurs in 16 million individuals chronically infected by
      the protozoan Trypanosoma cruzi in Latin America, and may lead to a dilated
      cardiomyopathy in 10-30% of patients. A vigorous cellular immune response holds
      parasitism in check. However, up to now, few T. cruzi proteins have been shown to
      be recognized by CD8+ T cells from Chagas disease patients. In this study, we
      designed 94 peptides derived from T. cruzi proteins cruzipain and FL-160,
      predicted to bind to HLA-A2 molcules. After in vitro binding assays to HLA
      A*0201, 26 peptides were selected, and their recognition by PBMC from Chagas
      disease patients was tested with the IFN-gamma ELISPOT assay. All 26 peptides
      were recognized by PBMC from at least one patient. Furthermore, a tetrameric HLA
      A*0201 complex built with the cruzipain 60-68 peptide that was frequently
      recognized in the periphery also bound to CD8+ T cells from a heart-infiltrating
      T cell line obtained from a single patient with Chagas disease cardiomyopathy.
      Thus, our results suggest that the recognition of CD8+ T cell epitopes in
      cruzipain and FL-160 may have a pathogenic or protective role in chronic Chagas
      disease.

PMID- 15848277
TI  - Cytokines and lymphocyte proliferation in patients with different clinical forms
      of chromoblastomycosis.
AB  - Chromoblastomycosis is a chronic, often debilitating, suppurative, granulomatus
      mycosis of the skin and subcutaneous tissues beginning after inoculation trauma.
      It occurs world-wide, but is more frequently observed in tropical countries such
      as Brazil. The disease is usually insidious, and the lesions increase slowly but
      progressively, not responding to the usual treatments and quite often
      reappearing. The host defense mechanism in chromoblastomycosis has not been
      extensively investigated. Some studies have focused on fungus-host interaction,
      showing a predominantly cellular immune response, with the activation of
      macrophages involved in fungus phagocytosis. Although phagocytosis did occur,
      death of fungal cells was rarely observed. The ability of Fonsecaea pedrosoi to
      produce secreted or cell wall-associated melanin-like components, protects
      against destruction by host immune cells in vitro. Until now, the T cell immune
      response in chromoblastomycosis is undefined. In the present work, it was shown
      that, in patients with the severe form of the disease, predominant production of
      IL-10 cytokine, low levels of IFN-gamma and inefficient T cell proliferation were
      induced. In contrast, in patients with a mild form of the disease, predominant
      production of IFN-gamma cytokine, low levels of IL-10 and efficient T cell
      proliferation were observed.

PMID- 15848278
TI  - A three-dimensional structure of Plasmodium falciparum serine
      hydroxymethyltransferase in complex with glycine and 5-formyl-tetrahydrofolate.
      Homology modeling and molecular dynamics.
AB  - Cytosolic Plasmodium falciparum serine hydroxymethyltransferase (pfSHMT) is a
      potential target for antimalarial chemotherapy. Contrasting with the other
      enzymes involved in the parasite folate cycle, little information is available
      about this enzyme, and its crystallographic structure is unknown yet. In this
      paper, we propose a theoretical low-resolution 3D model for pfSHMT in complex
      with glycine and 5-formyl tetrahydrofolate (5-FTHF) based on homology modeling by
      multiple alignment followed by intensive optimization, validation and dynamics
      simulations in water. Comparison between the active sites of our model and that
      of crystallographic Human SHMT (hSHMT) revealed key differences that could be
      useful for the design of new selective inhibitors of pfSHMT.

PMID- 15848279
TI  - Differential effects of uncharged aminoamide local anesthetics on phospholipid
      bilayers, as monitored by 1H-NMR measurements.
AB  - We have collected evidences of a "transient site" for the local anesthetics (LA)
      lidocaine, etidocaine, bupivacaine and mepivacaine in sonicated egg
      phosphatidylcholine (EPC) vesicles. The effects of the uncharged anesthetic
      species at a fixed LA/EPC ratio inside the bilayer were measured by chemical
      shifts (C.S.) and longitudinal relaxation times (T(1)) of the lipid hydrogens.
      Two sort of changes were detected: (I) decrease, indicating specific orientation
      of the LA aromatic ring (measured as up-field C.S. changes by the short-range
      ring-current effect) and less rotational freedom (smaller T(1) values) for EPC
      hydrogens such as the two glycerol-CH(2) and the choline-CH(2) bound to the PO(4
      ) group, probably due to the nearby presence of the LA; (II) increase, indicating
      the aromatic ring is now perpendicular to the orientation observed before
      (causing down-field changes in C.S.) and larger T(1) values for all the choline
      and glycerol hydrogens, as a result of LA insertion behind these well-organized
      bilayer regions. The less hydrophobic, linear and nonlinear (lidocaine and
      mepivacaine, respectively) aminoamide analogs provide similar effects-described
      in I; their hydrophobic counterparts (etidocaine and bupivacaine) also produced
      comparable effects (depicted in II). The preferential positioning and orientation
      of each LA inside the bilayer is then determined by its hydrophobic and steric
      properties. We propose that this "transient site" in the lipid milieu exists also
      in biological membranes, where it can modulates the access of the uncharged LA
      species to its site(s) of action in the voltage-gated sodium channel.

PMID- 15848280
TI  - Effect of phosphatidylglycerol on molecular organization of photosystem I.
AB  - Phosphatidylglycerol (PG) is the only anionic phospholipid in photosynthetic
      membrane. In this study, photosystem I (PSI) particles obtained from plant
      spinach were reconstituted into PG liposomes at a relatively high concentration.
      The results from visible absorption, fluorescence emission, and circular
      dichroism (CD) spectra reveal an existence of the interactions of PSI with PG. PG
      effect causes blue-shift and intensity decrease of Chl a peak bands in the
      absorption and 77 K fluorescence emission. The visible CD spectra indicate that
      the excitonic interactions for Chl a and Chl b molecules were enhanced upon
      reconstitution. Furthermore, more or less blue- or red-shift of the peaks
      characterized by Chl a, Chl b, and carotenoid molecules are also occurred.
      Simultaneously, an increase in alpha-helix and a decrease particularly in the
      disordered conformations of protein secondary structures are observed. In
      addition, the same effect also leads to somewhat more tryptophan (Trp) residues
      exposed to the polar environment. These results demonstrate that some alteration
      of molecular organization occurs within both the external antenna LHCI and PSI
      core complex after PSI reconstitution.

PMID- 15848281
TI  - Brief exposure to high magnetic fields determines microtubule self-organisation
      by reaction-diffusion processes.
AB  - A frequent feature of microtubule organisation in living systems is that it can
      be triggered by a variety of biochemical or physical factors. Under appropriate
      conditions, in vitro microtubule preparations self-organise by a reaction
      diffusion process in which self-organisation depends upon, and can be triggered
      by, weak external physical factors such as gravity. Here, we show that self
      organisation is also strongly dependent upon the presence of a high magnetic
      field, for a brief critical period early in the process, and before any self
      organised pattern is visible. These results provide evidence that external
      physical factors trigger self-organisation by way of an orientational bias that
      breaks the symmetry of the reaction-diffusion process. As microtubule
      organisation is central to many cell functions, this behaviour provides a
      mechanism by which strong magnetic fields can intervene in biological processes.

PMID- 15848282
TI  - Phase synchronization and coherence resonance of stochastic calcium oscillations
      in coupled hepatocytes.
AB  - The frequency of free cytosolic calcium concentration ([Ca(2+)]) oscillations
      elicited by a given agonist concentration differs between individual hepatocytes.
      However, in multicellular systems of rat hepatocytes and even in the intact
      liver, [Ca(2+)] oscillations are synchronized and highly coordinated. In this
      paper, we have investigated theoretically the effects of gap junction permeable
      to calcium and of the total Ca(2+) channel number located on endoplasmic
      reticulum on intercellular synchronization. Figures of ratio between mean
      oscillating frequency of coupled cells describe visually the process of phase
      locking. By virtue of a set of phase analysis, we can observe a gradual
      transition from synchronous behavior to nonsynchronous behavior. Furthermore, a
      signal-to-noise ratio in two dimensional parameter space (coupling strength-total
      Ca(2+) channel number) has suggested that, coherence resonance will occur for
      appropriate noise and coupling.

PMID- 15848283
TI  - A conformational alpha-helix to beta-sheet transition accompanies racemic self
      assembly of polylysine: an FT-IR spectroscopic study.
AB  - The self-assembly of polylysine chains with opposite chiral senses is an
      intriguing phenomenon, suggesting that subtle hydrational effects may be a
      driving force of protein aggregation. We have used FT-IR spectroscopy to
      characterize the alpha-helix-to-beta-sheet conformational transition that
      accompanies the aggregation of single and mixed enantiomers of polylysine. The
      preferential racemic self-assembly not only takes place at a lower temperature,
      but is also less prone to repulsive electrostatic interactions between lysine
      charged side chains, caused by decreasing pH (pD). While the process is generally
      irreversible, it yet appears to proceed in a stepwise manner through a sequence
      of thermodynamically, rather than kinetically controlled events involving gradual
      destabilization of alpha-helices. Interestingly, although the alpha/beta
      transition is in either case (single or mixed enantiomers) an endothermic
      process, it may also be induced by freezing of water, which leads to markedly
      more complete (and irreversible) aggregation of the mixed enantiomers. Relevance
      of these findings has been discussed in the context of protein aggregation
      studies.

PMID- 15848284
TI  - Proton translocation coupled to formate oxidation in anaerobically grown
      fermenting Escherichia coli.
AB  - Proton translocation, coupled to formate oxidation and hydrogen evolution, was
      studied in anaerobically grown fermenting Escherichia coli JW136 carrying
      hydrogenase 1 (hya) and hydrogenase 2 (hyb) double deletions. Rapid acidification
      of the medium by EDTA-treated anaerobic suspension of the whole cells or its
      alkalization by inverted membranes was observed in response to application of
      formate. The formate-dependent proton translocation and 2H(+)-K(+) exchange
      coupled to H(2) evolution were sensitive to the uncoupler, carbonylcyanide-m
      chlorophenylhydrazone, and to copper ions, inhibitors of hydrogenases. No pH
      changes were observed in a suspension of formate-pulsed aerobically grown
      ("respiring") cells. The apparent H(+)/formate ratio of 1.3 was obtained in cells
      oxidizing formate. The 2H(+)-K(+) exchange of the ATP synthase inhibitor N,N'
      dicyclohexylcarbodiimide-sensitive ion fluxes does take place in JW136 cell
      suspension. Hydrogen formation from formate by cell suspensions of E. coli JW136
      resulted in the formation of a membrane potential (Deltapsi) across the
      cytoplasmic membrane of -130 mV (inside negative). This was abolished in the
      presence of copper ions, although they had little effect on the value of Deltapsi
      generated by E. coli under respiration. We conclude that the hydrogen production
      by hydrogenase 3 is coupled to formate-dependent proton pumping that regulates
      2H(+)-K(+) exchange in fermenting bacteria.

PMID- 15848285
TI  - Polymerase chain reaction of nanoparticle-bound primers.
AB  - Using one or two primers respectively bound to the surface of Au nanoparticles
      (AuNPs) or magnetic nanoparticles (MNPs), polymerase chain reaction (PCR) based
      on nanoparticles was systemically studied, agarose gel electrophoresis and atomic
      force microscopy (AFM) were respectively used to detect and observe the PCR
      product. The results obtained indicated that with either one or two primers
      respectively bound to the nanoparticle surface, PCR can proceed successfully
      under optimized condition and is subject to certain rules, consequently a
      symmetric PCR technique and an asymmetric PCR technique based on nanoparticles
      have been developed. A kind of nanostructured aggregates can be constructed by a
      symmetric PCR using two nanoparticle-bound primers.

PMID- 15848286
TI  - Stopped-flow studies of guanine binding by calf spleen purine nucleoside
      phosphorylase.
AB  - The binding of guanine to calf spleen purine nucleoside phosphorylase at 20
      degrees C, in 20 mM Hepes-NaOH buffer, pH 7.0, at several ionic strength between
      5 and 150 mM was investigated using a stopped-flow spectrofluorimeter. The
      kinetic transients registered after mixing a protein solution with ligand
      solutions of different concentrations were simultaneously fitted by several
      association reaction models using nonlinear least-squares procedure based on
      numerical integration of the chemical kinetic equations appropriate for given
      model. It is concluded that binding of a guanine molecule by each of the binding
      sites is a two-step process and that symmetrical trimeric calf spleen purine
      nucleoside phosphorylase represents a system of (identical) interacting binding
      sites. The interaction is visible through relations between the rate constants
      and non-additivity of changes in "molar" fluorescence for different forms of PNP
      guanine complexes. It is also probable that electrostatic effects in guanine
      binding are weak, which indicates that it is the neutral form of the ligand which
      is bound and dissociated by PNP molecule.

PMID- 15848287
TI  - Molecular dynamics simulations of evolved collective motions of atoms in the
      myosin motor domain upon perturbation of the ATPase pocket.
AB  - A crucial point for mechanical force generation in actomyosin systems is how the
      energy released by ATP hydrolysis in the myosin motor domain gives rise to the
      movement of the myosin head along the actin filament. We assumed the signal of
      the ATP hydrolysis to be transmitted as modulated atomic vibrations from the
      nucleotide-binding site throughout the myosin head, and carried out 1-ns all-atom
      molecular dynamics simulations for that signal transmission. We distributed the
      released energy to atoms located around the ATPase pocket as kinetic energies and
      examined how the effect of disturbance extended throughout the motor domain. The
      result showed that the disturbance signal extended over the motor domain in 150
      ps and induced slowly varying collective motions of atoms at the actin-binding
      site and the junction with the neck, both of which are relevant to the movement
      of the myosin head along the actin filament. We also performed a principal
      component analysis of thermal atomic motions for the motor domain, and the first
      principal component was consistent with the response to the disturbance given to
      the ATPase pocket.

PMID- 15848289
TI  - Mechanisms of quinolone resistance in Escherichia coli and Salmonella: recent
      developments.
AB  - Fluoroquinolones are broad-spectrum antimicrobials highly effective for treatment
      of a variety of clinical and veterinary infections. Their antibacterial activity
      is due to inhibition of DNA replication. Usually resistance arises spontaneously
      due to point mutations that result in amino acid substitutions within the
      topoisomerase subunits GyrA, GyrB, ParC or ParE, decreased expression of outer
      membrane porins, or overexpression of multidrug efflux pumps. In addition, the
      recent discovery of plasmid-mediated quinolone resistance could result in
      horizontal transfer of fluoroquinolone resistance between strains. Acquisition of
      high-level resistance appears to be a multifactorial process. Care needs to taken
      to avoid overuse of this important class of antimicrobial in both human and
      veterinary medicine to prevent an increase in the occurrence of resistant
      zoonotic and non-zoonotic bacterial pathogens that could subsequently cause human
      or animal infections.

PMID- 15848290
TI  - Susceptibility and resistance genes to fluoroquinolones in methicillin-resistant
      Staphylococcus aureus isolated in 2002.
AB  - The activity of six fluoroquinolones (FQs) was determined against 100 methicillin
      resistant Staphylococcus aureus (MRSA) isolated in 2002 along with mutations in
      the grlA and gyrA genes and in the norA promoter of these isolates. Of the
      isolates tested, 97% had mutations in grlA and gyrA. A single mutation in grlA
      and gyrA resulted in a decrease of susceptibility to old generation FQs
      (norfloxacin, enoxacin, ciprofloxacin, fleroxacin, sparfloxacin and levofloxacin)
      but not to new generation FQs (gatifloxacin and moxifloxacin). Double mutations
      of both grlA and gyrA resulted in high-level resistance to all FQs tested. All
      norA mutants (15%) contained double mutations in grlA and gyrA and showed no
      decrease of MIC in the presence of reserpine, which is known to inhibit the drug
      efflux pump. Our results showed that double mutations in grlA and gyrA were
      necessary for the expression of high-level resistance to new generation FQs. As
      different FQ-resistant mutants occur in the same PFGE type, FQ-resistant MRSA may
      well develop individually.

PMID- 15848291
TI  - Comprehensive in vitro evaluation of cefepime combined with aztreonam or
      ampicillin/sulbactam against multi-drug resistant Pseudomonas aeruginosa and
      Acinetobacter spp.
AB  - Pseudomonas aeruginosa and Acinetobacter spp. are becoming increasingly resistant
      to antimicrobial agents, and serious infections caused by these organisms often
      require combination therapy. Interactions of cefepime with either aztreonam (P.
      aeruginosa; n=46) or ampicillin/sulbactam (Acinetobacter spp.; n=34) were
      investigated by the chequerboard synergy method against isolates with various
      resistance phenotypes, including resistance to imipenem (36 P. aeruginosa and 19
      Acinetobacter spp.). Synergy or partial synergy interactions occurred with 56.5%
      of P. aeruginosa and 88.2% of Acinetobacter spp. strains examined. Among the
      imipenem-resistant strains, synergy or partial synergy interactions were observed
      in 47.2% of P. aeruginosa and 84.2% of Acinetobacter spp. strains. In addition,
      the vast majority of impenem-resistant strains showed MIC values within
      achievable concentrations in plasma for at least one of the antimicrobials
      evaluated in the combination. The role of combination antimicrobial therapy in
      the treatment of severe infections caused by multidrug-resistant P. aeruginosa
      and Acinetobacter spp. should be further evaluated to maximize favourable
      clinical outcomes.

PMID- 15848292
TI  - Antimicrobial peptides are among the antagonistic metabolites produced by
      Bifidobacterium against Helicobacter pylori.
AB  - Sixty acid-resistant Bifidobacterium isolates were recovered from human faeces
      and identified by genus-specific PCR and RAPD-PCR. Helicobacter pylori strains
      were isolated from gastric biopsies and identified by species-specific PCR.
      Twenty-four of the 60 Bifidobacterium isolates were considered to be different
      strains by RAPD-PCR. Six of the twenty-four different strains were shown to
      inhibit H. pylori. These antagonistic effects were related to heat-stable
      proteinaceous compounds, resistant to heating at 100 degrees C for 10 min, but
      sensitive to proteases. H. pylori stains showed variable resistance to
      therapeutic antibiotics (metronidazole and clarithromycin), while all the
      selected bifidobacteria showed intrinsic resistance to metronidazole. These
      potentially probiotic bifidobacteria were able to inhibit the growth of both
      antibiotic sensitive and resistant H. pylori strains. Thus, the synthesis of
      antimicrobial peptides could be one of the mechanisms of bifidobacteria to combat
      H. pylori infections.

PMID- 15848293
TI  - The effect of surface charge on the disposition of liposome-encapsulated
      gentamicin to the rat liver, brain, lungs and kidneys after intraperitoneal
      administration.
AB  - The disposition of gentamicin to the normal rat brain, lung, kidney and liver was
      studied at intervals of 1, 2, 4, 6 and 8h after intraperitoneal injection of
      gentamicin encapsulated in positive, negative and neutral liposomes. Compared
      with the control, which was treated with free gentamicin, liposomes were
      associated with higher concentrations of gentamicin in the brain and liver, while
      concentrations were lower in the kidney. The average concentrations of gentamicin
      in the liver and the brain were highest with positive liposomes, while,
      gentamicin concentrations in the kidneys and lungs were not influenced by surface
      charge of the liposomes. These observations have important implications on the
      selective delivery of gentamicin to tissues and on the intraperitoneal route of
      administration.

PMID- 15848294
TI  - Optimization of empirical antibiotic selection for suspected Gram-negative
      bacteraemia in the emergency department.
AB  - A 1-year prospective study of patients with a positive blood culture and admitted
      through the emergency department (ED), was conducted to detect incidence and risk
      factors for resistance of Enterobacteriaceae to gentamicin and ciprofloxacin. A
      total of 245 emergency department-admitted patients had positive blood cultures,
      of which 131 (54%) grew Enterobacteriaceae. Of these 131 isolates, 32 (24%) were
      resistant to gentamicin and 37 (28%) to ciprofloxacin. Risk factors, by
      multivariate analysis, for gentamicin and ciprofloxacin resistance were: male
      gender (P<0.05 and P<0.01, respectively), nursing home residence (P<0.001),
      diabetes mellitus (P<0.05) and presence of a foreign body (P<0.05 and P<0.005).
      An additional risk factor for ciprofloxacin resistance was recent hospitalisation
      (P<0.05). These data facilitate optimal selection of empirical antibiotic
      treatment of suspected Gram-negative infections, and may contribute to improved
      patient outcome and optimal use of antibiotics.

PMID- 15848295
TI  - Antimicrobial and healing activity of kefir and kefiran extract.
AB  - Kefir and its insoluble polysaccharide, kefiran, were both tested for
      antimicrobial and cicatrizing activities against several bacterial species and
      Candida albicans using an agar diffusion method. Comparator antimicrobials were
      also tested. Cicatrizing experiments were carried out on Wistar rats with induced
      skin lesions and Staphylococcus aureus inoculation, using a topical application
      of a 70% kefir gel. Both kefir and kefiran showed some activity against all
      organisms tested; the highest activity was against Streptococcus pyogenes.
      Cicatrizing experiments using 70% kefir gel had a protective effect on skin
      connective tissue and 7 days treatment enhanced wound healing compared with 5
      mg/kg of neomycin-clostebol emulsion.

PMID- 15848296
TI  - Comparative pharmacodynamics of the new fluoroquinolone ABT492 and levofloxacin
      with Streptococcus pneumoniae in an in vitro dynamic model.
AB  - The kinetics of killing of Streptococcus pneumoniae exposed to ABT492 or
      levofloxacin were compared. S. pneumoniae ATCC 49619 and four ciprofloxacin
      resistant clinical isolates, S. pneumoniae 1149, 391, 79 and 804, were exposed to
      ABT492 and levofloxacin as a single dose in a dynamic model that simulates human
      pharmacokinetics of the quinolones. With S. pneumoniae ATCC 49619 eight-fold
      ranging AUC/MIC ratios (60-500 h) were simulated for each quinolone. In addition,
      two larger AUC/MICs, i.e., 1080 and 2150 h for ABT492 and 1460 and 3660 h for
      levofloxacin which correspond to 100 and 200 mg doses of ABT492 and 200 and 500
      mg doses of levofloxacin, respectively, were mimicked. Each ciprofloxacin
      resistant organism was exposed to the clinical doses of ABT492 (400 mg) and
      levofloxacin (500 mg); the respective AUC/MIC ratios were from 580 to 3470 h and
      from 28 to 110 h. At comparable AUC/MICs (from 60 to 500 h), regrowth of S.
      pneumoniae ATCC 49619 followed initial killing, and the times to regrowth were
      longer with levofloxacin than ABT492. However, no regrowth of S. pneumoniae ATCC
      49619 occurred at the higher AUC/MICs of ABT492 (1080 and 2150 h) and
      levofloxacin (1460 and 3660 h). Killing of S. pneumoniae 1149, 391 and 79 without
      bacterial regrowth, was provided by ABT492 (AUC/MIC 3470, 2310 and 1160 h,
      respectively) but not levofloxacin (AUC/MIC 55, 110 and 28 h, respectively).
      Regrowth of S. pneumoniae 804 was observed with both ABT492 and levofloxacin
      (AUC/MIC 580 and 55 h, respectively). Areas between the control growth curve and
      the time-kill curve (ABBCs) for ABT492 against S. pneumoniae 1149, 391 and 79
      were 2.6-4.2 times larger than the respective ABBCs for levofloxacin, whereas
      similar ABBCs were found with S. pneumoniae 804 exposed to both quinolones. These
      findings predict significantly greater efficacy of ABT492 than levofloxacin at
      clinically achievable AUC/MIC ratios against ciprofloxacin-resistant S.
      pneumoniae and similar efficacies of the two quinolones against susceptible
      organisms.

PMID- 15848297
TI  - Meningitis due to methicillin-resistant Staphylococcus aureus (MRSA): review of
      10 cases.
AB  - We evaluated retrospectively, 10 MRSA meningitis cases in our hospital that
      occurred between January 1999 and June 2004. All were post-neurosurgical and were
      considered to have hospital-acquired meningitis. Fever, leukocytosis, variable
      conscious levels were the most common findings. Six patients were treated with
      regimens including teicoplanin, and four with vancomycin. Mean duration of
      treatment was 23.5+/-18.8 days (range, 3-60 days). One patient died. In cases of
      MRSA meningitis, intravenous vancomycin is the mainstay of therapy. However, six
      of these 10 patients were successfully treated with regimens including
      teicoplanin, suggesting that this agent may be an alternative to vancomycin in
      the therapy of these cases.

PMID- 15848298
TI  - Spectrum of antiviral activity of o-(acetoxyphenyl)hept-2-ynyl sulphide (APHS).
AB  - Since some antiviral drugs have a broad spectrum of action, the aim of this study
      was to assess whether o-(acetoxyphenyl)hept-2-ynyl sulphide (APHS), a recently
      described inhibitor of human immunodeficiency virus type 1 (HIV-1) replication,
      has an effect on the replication of other retroviruses, (-) and (+) RNA viruses
      and DNA viruses. APHS did not affect the replication of feline immunodeficiency
      virus, HIV-2 and a HIV-1 strain resistant to non-nucleoside reverse transcriptase
      inhibitors (NNRTI). APHS could also not inhibit the replication of the RNA
      viruses, respiratory syncytium virus or mouse hepatitis virus. In contrast, APHS
      did inhibit the replication of wild-type herpes simplex virus type 1 (HSV-1) as
      well as acyclovir-resistant HSV-1 and HSV-2 mutant. These results suggest that
      APHS is a NNRTI of HIV-1 replication, but not HIV-2 replication, and that APHS is
      an inhibitor of both HSV-1 and HSV-2 replication.

PMID- 15848299
TI  - Dynamics of the antiviral activity of N-methanocarbathymidine against herpes
      simplex virus type 1 in cell culture.
AB  - N-Methanocarbathymidine [(N)-MCT], a thymidine analogue, exhibits potent activity
      in cell culture against herpes simplex virus1 (HSV-1). (N)-MCT showed higher
      antiviral activity than ganciclovir (GCV). Continuous treatment of Vero cells
      with (N)-MCT immediately or 10 h post-infection (p.i.) fully prevented the
      development of viral infection. However, when infected cells were treated with
      (N)-MCT at 12 h p.i., there was only a partial inhibition (ca. 50%).
      Additionally, continuous treatment of infected cells with (N)-MCT for about 48 h
      was sufficient to achieve full prevention of viral infection without further
      treatment. These findings suggest the complete loss of herpes simplex thymidine
      kinase (HSV-tk) activity occurs after 48 h of treatment with (N)-MCT. This study
      helps to understand the mechanism and dynamics of antiHSV activity of (N)-MCT,
      which is necessary for its future development as an antiviral drug.

PMID- 15848300
TI  - Inhibitory activity of bovine lactoferrin against echovirus induced programmed
      cell death in vitro.
AB  - Lactoferrin is a glycoprotein and plays an important role in defence against
      pathogens. Although the antiviral activity of lactoferrin is one of the major
      biological functions of such protein, the mechanism of action is still under
      debate. The effect of lactoferrin on echovirus 6 infection in vitro was analysed
      and results showed that (i) cells infected with echovirus 6, died as a result of
      apoptosis and that (ii) programmed cell death was inhibited by lactoferrin
      treatment. In this report, we demonstrate that lactoferrin can exert its anti
      enteroviral activity by preventing viral-induced apoptosis.

PMID- 15848301
TI  - Patterns of antibiotic use among adults and parents in the community: a
      questionnaire-based survey in a Greek urban population.
AB  - The purpose of this study was to look for factors that affect attitudes to
      antibiotic use in Greek urban settings. By using a questionnaire-based survey, we
      conducted 323 face-to-face interviews (173 adults, 150 carers of children). In
      the adult group, 74.6% admitted using non-prescribed antibiotics, while only
      22.7% of parents had administered non-prescribed antibiotics to their children.
      Around 50% of adults discontinued therapy earlier, more than 10% did not follow
      the correct dosage instructions and about 55% admitted using leftover
      antibiotics. Of the parents, 18.7% discontinued therapy earlier and 7.3% admitted
      keeping leftover antibiotics. Our results showed that adults were likely to show
      unsatisfactory compliance and to use non-prescribed antibiotics, while parents
      were less likely to use non-prescribed antibiotics for their children and were
      more compliant.

PMID- 15848302
TI  - Reversible dilated cardiomyopathy associated with amphotericin B treatment.
AB  - We report two patients, who developed dilated cardiomyopathy and subsequent
      congestive heart failure after treatment with amphotericin B (AmB). The
      echocardiographic findings and the symptoms of heart failure resolved after the
      discontinuation of the drug. The clinical data from our cases and two similar
      cases reported in the literature suggest that the presence of other factors
      predisposing to cardiac dysfunction may facilitate the occurrence of this rare
      side effect.

PMID- 15848303
TI  - Clinical development of antimicrobial peptides.

PMID- 15848304
TI  - Antibiotic resistance of Helicobacter pylori isolated in Split, Southern Croatia.

PMID- 15848305
TI  - Low macrolide resistance in Streptococcus pyogenes in Southern Argentina.

PMID- 15848306
TI  - Complex pulmonary aspergilloma treated with single stage cavernostomy and
      myoplasty.
AB  - OBJECTIVE: Complex pulmonary aspergilloma (CPA) following pulmonary tuberculosis
      may lead to massive and fatal hemoptysis. Pulmonary resection, as initial
      therapy, carries high morbidity and mortality. Resection is contraindicated in
      patients with compromised lung function (FEV1<40%) and in those with bilateral
      disease. We reviewed the results of patients undergoing single stage cavernostomy
      and myoplasty as an alternative therapy in patients with normal and compromised
      lung function. METHODS: Patients suffering from recurrent massive hemoptysis
      (600ml/24h or >150ml/h) due to CPA were selected for single stage cavernostomy
      and myoplasty. We performed rib resection, cavernostomy, closure of the bronchial
      openings and total/partial obliteration of the cavity with a muscle flap as a
      single stage technique in patients with CPA regardless of pulmonary function or
      bilateral disease. Patients began oral Itracanozole two weeks prior to surgery
      and continued for 3 months post-operatively. RESULTS: Three women and four men
      (median age 38 years; range 24-59 years) with CPA were evaluated. Four patients
      had either bilateral disease or compromised lung function. Pectoralis major
      muscle was used for the myoplasty in five and trapezius or latissimus dorsi in
      the other two patients. The median number of bronchial fistulae closed during the
      surgery was six (range 2-12). Blood loss was minimal (median 227ml). Two patients
      underwent successful re-exploration for significant air leak. The median hospital
      stay was 9 days (6-27days). Six patients are alive and hemoptysis free (median
      follow-up 57.2 months). CONCLUSIONS: Cavernostomy and myoplasty as a single stage
      technique is safe and reliable in the management of patients with complex
      pulmonary aspergilloma. Morbidity is low even in patients with compromised lung
      function or bilateral disease.

PMID- 15848307
TI  - Video assisted thoracoscopic re-sympathetic surgery in the treatment of re
      sweating hyperhidrosis.
AB  - OBJECTIVE: The characteristics and causes of re-sweating after sympathetic
      surgery in hyperhidrosis patients have yet to be clearly documented due primarily
      to low incidence of re-sympathetic surgery. The purpose of this study is to
      identify the causes of re-sweating following sympathetic surgery, and to assess
      the outcomes of re-sympathetic surgery. METHODS: From February 1997 to July 2003,
      36 patients underwent re-sympathetic surgery in order to treat re-sweating.
      Patients originally underwent sympathetic surgery due to facial (14 cases),
      palmar (21 cases), and axillary (1 case) hyperhidrosis. RESULTS: Sympathectomy
      was performed as a primary surgical intervention in 7 cases (19.4%),
      sympathicotomy in 12 cases (33.3%), and sympathetic clipping in 17 cases (47.3%).
      Thirteen patients complained of re-sweating on both sides, and 23 patients
      exhibited unilateral re-sweating. The onset of re-sweating occurred after an
      average of 3.1+/-3.4 months (range, 1-12 months) after the operation. The causes
      of re-sweating after sympathetic surgery included an intact sympathetic chain in
      4 cases (11.1%), incomplete resection in 6 cases (16.7%), partial reattachment in
      6 cases (16.7%), improper ganglion location in 4 cases (11.1%), clip slipping out
      in 11 cases (30.5%), and unknown in 5 cases (13.9%). Twenty-seven patients
      (75.0%) exhibited re-sweating within 3 months, and 9 patients (25.0%) experienced
      re-sweating after 6 months. During the second operation, sympathicotomy was
      performed in 20 cases (55.6%) and sympathetic clipping in 16 cases (44.4%) in
      which 32 patients (88.9%) reported decreased sweating. CONCLUSIONS: Surgical
      errors during the initial operation constituted the main cause of re-sweating
      following sympathetic surgery. Re-sympathetic surgery was necessary in order to
      treat re-sweating, and was associated with favorable outcomes.

PMID- 15848308
TI  - Assessment of node dissection for clinical stage I primary lung cancer by VATS.
AB  - OBJECTIVE: The feasibility of systematic node dissection (SND) for stage I
      primary lung cancer by video-assisted thoracic surgery (VATS) remains
      controversial. The aim of this study was to assess the feasibility of SND by
      VATS. METHODS: Four hundred and eleven patients with clinical stage I primary
      lung cancer were enrolled in this study. Two hundred and twenty-one patients,
      VATS group, underwent a major pulmonary resection with SND by VATS through a
      minithoracotomy (30-70mm) and two access ports; 190 patients, open thoracotomy
      (OT) group, did so through anterolateral thoracotomy. The two groups were
      compared regarding clinical data including number of dissected nodes in each
      nodal station for evaluating the feasibility of SND by VATS. RESULTS: In the
      right side, the total number (N) of nodes dissected (VATS 31 vs OT 31, P=0.899),
      N of mediastinal nodes dissected (20 vs 21, P=0.553), and N of dissected nodes in
      each nodal station were similar between the two groups. In the left side, total N
      of nodes dissected (28 vs 27, P=0.714), N of mediastinal nodes dissected (16 vs
      17, P=0.333), and N of dissected nodes in each nodal station were similar between
      the two groups. There were three (1.4%) and five (2.6%) operation related deaths
      in the VATS group and OT group, respectively (P=0.48). Chest tube duration was
      shorter in the VATS group than the OT group (5.8 vs 7.6 days, P=0.001). The
      incidences of chylothorax, recurrent laryngeal nerve injury and pleural effusion
      requiring thoracentesis after surgery were similar between the two groups (3 vs
      4, P=0.709; 5 vs 3, P=0.480, 3 vs 8, P=0.122). The 5-year actuarial recurrence
      free survival rate and cumulative survival rate of pathological stage IA cases
      were similar between the two groups (88.6 vs 92.4%, P=0.698; 92.9 vs 86.5%,
      P=0.358). CONCLUSIONS: The SND by VATS was as technically feasible as SND through
      OT regarding number of dissected nodes and morbidity. It seems acceptable as an
      oncological treatment for clinical stage I lung cancer.

PMID- 15848309
TI  - Metachronous adrenal masses in resected non-small cell lung cancer patients:
      therapeutic implications of laparoscopic adrenalectomy.
AB  - OBJECTIVE: In literature only few reports focused on the resection of solitary
      adrenal gland metastasis in patients operated on for non-small cell lung cancer
      (NSCLC). We report our experience on laparoscopic adrenalectomy for suspected or
      confirmed metachronous solitary adrenal metastasis from NSCLC and discuss its
      therapeutic role. METHODS: From June 1993 to March 2003, 14 patients (pts), who
      had been undergone lung resection for NSCLC, with suspected or confirmed solitary
      adrenal gland metastasis at the follow-up, underwent 15 laparoscopic
      adrenalectomy (in 1 patient it was bilateral). All the patients had enlarged
      adrenal glands at the abdominal ultrasound or CT. All but 2 pts underwent at
      least 1 adrenal fine needle aspiration. All the patients underwent a careful
      staging to exclude other sites of metastasis. The adrenal gland was in 6 cases
      the right, in 9 cases the left. RESULTS: In 7 cases we had a preoperative
      cytological diagnosis of metastasis. In 1 case adrenalectomy was not performed
      because of infiltration of vena cava and in 1 case it was necessary to perform a
      small laparotomy because of bleeding. The pathologic examination confirmed in 11
      cases a NSCLC metastasis while in 4 cases it was a cortical adenoma. Regarding
      the 10 patients with NSCLC metastases, 3 are still alive and well at 37-80 months
      from the lung resection. One patient (who underwent bilateral adrenalectomy) is
      still alive at 44 months with local relapse. Two patients died 5 and 6 months
      after the adrenalectomy for other causes, 1 died at 14 months for local and
      systemic relapse and the remaining 3 patients died at 12 to 38 months for
      systemic relapse. CONCLUSIONS: Laparoscopic adrenalectomy in patients resected
      for NSCLC is a safe mini-invasive procedure. Even though this series is still too
      small, laparoscopic adrenalectomy should be considered an effective therapeutic
      tool in case of progressive adrenal gland enlargement, also with negative
      cytological examinations. A bigger series and other institution experiences will
      clarify its oncological value.

PMID- 15848310
TI  - Extended donor criteria for lung transplantation--a clinical reality.
AB  - OBJECTIVE: Standard lung donor criteria have been established on opinions and
      individual experiences rather than on existing evidence. Since the scarcity of
      donor organs is one of the major limitations to lung transplantation, extension
      of donor lung criteria might considerably increase the donor pool. This study
      therefore evaluates the outcome, achieved with the use of extended donors versus
      standard donors and aims to redefine lung donor criteria. METHODS: We performed a
      retrospective analysis of 98 consecutive primary lung transplantations from 94
      donors from 1/2001 to 12/2002. Donors were classified as extended if they
      fulfilled at least one criteria: age >55 years, PaO(2) at FiO(2)/PEEP 5 <300mmHg,
      tobacco history >20 pack years, inhalative drug abuse, presence of infiltration
      on chest X-ray or purulent secretions at bronchoscopy. Recipients were stratified
      in two groups according to whether they received a 'standard' or 'extended'
      organ. Postoperative complications, extubation time, ICU and hospital stay and
      survival were compared. RESULTS: Twenty-three (24.5%) donors were extended.
      Twenty-six recipients (26.55%) received organs from extended donors. Differences
      in intubation times (12+/-2 days standard vs. 14+/-5 days extended, P=0.70), ICU
      stay (16+/-2 days standard vs. 18+/-5 days extended, P=0.74) and hospital stay
      (38+/-4 days standard vs. 40+/-6 days extended, P=0.71) were not statistically
      significant. Postoperative bleeding rates were comparable (n=14 standard vs. n=3
      extended) as well as bronchial anastomotic complications (n=7 standard vs. n=3
      extended). Three months survival was 88.89% in the standard group vs. 92.31% in
      the extended group. One year survival is comparable as well with 81.94 vs.
      84.62%, respectively. CONCLUSIONS: The use of lung donors who fail to meet
      standard criteria does not impair short and medium term results compared to
      standard lung donors. The impact on long term development of BOS has yet to be
      evaluated. The strict application of standard lung donor criteria excludes a
      considerable number of lungs potentially suitable for transplantation, thus
      liberalisation of donor criteria might help to overcome donor shortage.

PMID- 15848311
TI  - Extended donor lungs: eleven years experience in a consecutive series.
AB  - OBJECTIVE: The aim of this study was to delineate the profile of extended donor
      lungs in comparison to ideal donor lungs and to analyse their outcome. Particular
      attention was given to donor lungs with a low PaO(2) (<250mmHg) before harvesting
      or with multiple extended criteria. METHODS: Between 1993 and 2003, 148 patients
      (79 women, 69 men, mean age 39.9 years) underwent lung transplantation.
      Indications were cystic fibrosis in 35.8%, emphysema in 26.4%, pulmonary fibrosis
      in 12.2%, pulmonary hypertension in 9.5%, and others in 16.1%. Donor data and
      recipients medical files were reviewed. Criteria for donor lungs were considered
      extended if one or more of the following criteria were met: age >55 years,
      smoking >20 pack-years, PaO(2) before harvesting <300mmHg, pathologic chest X
      ray, and purulent secretion at bronchoscopy. A comparison between recipients from
      ideal and from extended donor lungs was performed with respect to the median
      duration of mechanical ventilation, the median length of stay at the intensive
      care unit, postoperative complications, the 30-day and the 1-year survival, and
      the 6-month follow-up spirometry. RESULTS: Sixty-three (42.6%) donor lungs were
      considered extended and 20 (31.7%) met more than one criteria. Outcome comparison
      between recipients from ideal (I) and extended (II) donor lungs did not
      statistically differ in postoperative complications (18.8% (I) vs. 26.9% (II),
      P=0.32), mean duration of mechanical ventilation (d) (4.4+/-2.7 (I) vs. 2.6+/-2.1
      (II), P=0.2), mean length of stay at the ICU (d) (11.5+/-8.8 (I) vs. 9.2+/-6.9
      (II), P=0.4), 6-month pulmonary function (FEV1=83+/-23% of the predicted value
      (I) vs. 82+/-18% (II), P=0.81), 30-day survival (90.6% (I) vs. 93.7% (II),
      P=0.56), 1-year survival (83.5% (I) vs. 81% (II), P=0.83). Thirty-day survival
      was also comparable even in recipients from donor lungs with PaO(2)<250mmHg (n=8)
      (90.6% (I) vs. 87.5%, P=0.57). The number of extended criteria had no impact on
      the outcome. The combination of PaO(2)<300mmHg with purulent secretion at
      bronchoscopy seemed to influence the early outcome of recipients from extended
      donor lungs negatively. CONCLUSIONS: Our results suggest that the use of selected
      extended donor lungs does not compromise the outcome after transplantation.
      PaO(2) <250mmHg before harvesting of the lungs is not an absolute contra
      indication for transplantation.

PMID- 15848312
TI  - Application of HVJ-liposome mediated gene transfer in lung transplantation
      distribution and transfection efficiency in the lung.
AB  - OBJECTIVE: A novel hemagglutinating virus of Japan (HVJ)-liposome-mediated gene
      transfer system has been shown to have benefits of a high efficiency of
      transfection and low immunogenicity. The aims of this study were to determine the
      effect of re-transfection of the HVJ-liposome system via the airway, and to
      quantify the distribution of gene expression between transtracheal and
      transplantation approaches. METHODS: Beta-galactosidase (beta-gal) plasmid DNA
      was introduced into lung tissues using the HVJ-liposome method. Two groups of
      Sprague-Dawley (SD) rats received intratracheal instillation of 10 microg of the
      beta-gal gene, once on Day 0 in 1 group (Group Tb-1, n=4) and 3 times on Days 0-2
      in another (Group Tb-3, n=4). In a third group of SD rats (Group Tx, n=5), an
      orthotopic left lung transplantation was performed after the donor lung was
      flushed with an HVJ-liposome complex solution and preserved for 1h. Gene
      expression and distribution in lung tissue was then quantified by counting the X
      gal stained cells. RESULTS: Both the transtracheal and transplantation approaches
      resulted in low levels of transfection in the vascular endothelial cells (0.2+/
      0.1 and 4.0+/-1.8%), respectively, but a moderate degree of transfection to the
      airway (11.0+/-7.1 and 28.0+/-20.7%) and alveolar cells (3.0+/-1.8 and 6.0+/
      3.6%). Three repetitive injections via the airway increased gene expression in
      airway epithelial cells of 41.0+/-12.0% compared with the single administration
      of 11.0+/-4.3%. CONCLUSIONS: Our results suggest that the repeated transtracheal
      gene transfection using HVJ-liposome may have benefits for treatment of problems
      after lung transplantation. In addition, gene transfer using a flushing solution
      during harvest may provide an opportunity for gene manipulation in the setting of
      lung transplantation.

PMID- 15848313
TI  - Surfactant pretreatment ameliorates ischemia-reperfusion injury of the lung.
AB  - OBJECTIVE: To investigate whether surfactant pretreatment provides lung
      protection in an animal model of lung ischemia-reperfusion injury (LIRI).
      METHODS: Male Sprague-Dawley rats (n=100) were randomised to receive
      intratracheally administered surfactant or no pretreatment. One hour thereafter,
      animals underwent 120min of warm ischemia of the left lung, or were sham
      operated. A third group served as healthy untreated controls. Animals were killed
      on day 1, 3 or 7. Blood gas values were measured and lung compliance was
      recorded. Broncho-alveolar lavage fluid (BALf) was obtained to assess the amount
      of alveolar protein, the ratio of small to large aggregate surfactant
      phospholipids (SA/LA ratio), and leukocyte infiltration (granulocytes,
      macrophages and lymphocytes, measured by Flow Cytometry). RESULTS: LIRI resulted
      in a mortality rate of 17% and significantly decreased lung compliance and PaO(2)
      (day 1 and 3 P<0.001, day 7 P<0.05) as compared to sham-operated and healthy
      controls. On day 1 more protein was present in the alveoli of ischemic lungs
      (P<0.001) than in sham-operated and healthy controls. Furthermore, LIRI resulted
      in an increased SA/LA ratio in the left lung on day 1 (P<0.05) and caused
      infiltration of granulocytes (day 1, 3 and 7 (P<0.01)), macrophages (day 3
      (P<0.05) and 7 (P<0.01) and lymphocytes (day 3 and 7 (P<0.01)) in the BALf as
      compared to sham-operated and healthy controls. Surfactant pretreatment improved
      survival, lung compliance (day 3 P<0.001) and PaO(2) (day 1, 3 (P<0.01 and 7
      (P<0.05)). It also reduced protein leakage (P<0.05) and prevented an increase in
      the SA/LA ratio (P<0.01). Although the number of macrophages and granulocytes in
      the BALF was increased on day 1 and 3 (P<0.01) after surfactant pretreatment as
      compared to all other groups, the number of lymphocytes was reduced on day 3
      (P<0.05). CONCLUSIONS: The present study shows that surfactant pretreatment
      enhances recovery of lung function and lung mechanics after LIRI, resulting in
      normal parameters from day 3 onwards. Surfactant pretreatment in this LIRI model
      may provide useful information to improve donor lung function after lung
      transplantation.

PMID- 15848314
TI  - Impaired circulating dendritic cell reconstitution identifies rejecting
      recipients after clinical heart transplantation independent of rejection therapy.
AB  - OBJECTIVE: Dendritic cell (DC) mediated allo-antigen presentation to host antigen
      specific T-lymphocytes initiates acute allograft rejection. We investigated
      peripheral blood DC (PBDC) incidence and DC subset reconstitution in relation to
      histological diagnosis of acute cellular rejection (AR) and administration of
      rejection therapy after clinical heart transplantation (post-HTx). METHODS:
      Venous blood from 20 HTx recipients under standard immunosuppression was
      collected during serial endomyocardial biopsy (EMB) prior to administration of
      rejection therapy in a 9-month follow-up post-HTx. Echocardiographic assessment
      of allograft function during EMB was performed to distinguish clinical necessity
      for rejection therapy within histologically rejecting patients (R). Myeloid (mDC)
      and plasmacytoid (pDC) subsets identified by flow-cytometry were analysed for
      different ISHLT rejection grades. Circulating PBDC incidence and mDC/pDC ratio
      were compared sequentially between non-rejecting (NR) recipients and R patients
      treated (3A(+)) or not-treated (3A(-)) with rejection therapy during follow-up.
      RESULTS: Eleven samples from biopsy-proven AR episodes (AR(+): ISHLT>or=3) were
      compared to 89 samples from non-rejection episodes (AR(-): ISHLT grade 0, n=52;
      grade 1, n=29; grade 2, n=8). We observed an inverse correlation of mDCs (P<0.05)
      but not pDCs with increasing rejection grade. PBDC incidence and mDC/pDC ratio
      were low in blood samples obtained during AR (P<0.05 and P<0.01, respectively).
      Both PBDCs and mDC/pDC ratio decreased during each AR episode (P<0.05).
      Comparison of 3A(+) and 3A(-) rejectors with NR patients after 12 weeks post-HTx
      revealed lower PBDC incidence (P<0.01) and mDC/pDC ratio (P<0.05) for R patients,
      independent of rejection therapy. CONCLUSIONS: Defective DC subset reconstitution
      by dendritic cell profiling identifies patients at risk for AR after 3 months
      post-HTx. This finding may contribute to further optimization of
      immunosuppressive treatment strategies after clinical heart transplantation.

PMID- 15848315
TI  - Ten year survival after paediatric heart transplantation: a single centre
      experience.
AB  - OBJECTIVE: To report 10 years survival in children under the age of 16 years
      undergoing heart transplantation in a single institution. METHODS: One hundred
      and thirty nine/one hundred and ninety three patients (73%) survived more than 1
      year after transplant. Seventy four (53%) of these survived more than 10 (10.0
      20.1) years. Age at operation was 10 days-15.5 (mean 8.1) years. Patients were
      maintained on ciclosporin and azathiaprine alone. Routine steroids only given to
      4 patients for either persistent rejection or deteriorating renal function.
      Rejection diagnosed on clinical or echocardiographic grounds. No routine biopsies
      were performed. Bi-annual coronary angiography was used to diagnose graft
      coronary disease. RESULTS: Graft coronary disease was found in 8 patients (11%),
      2 were re-transplanted and have survived 4.3-7.2 years since. Two patients are
      alive without intervention 2.0-13.0 years from initial diagnosis. Two patients
      have undergone interventional procedures 11 and 16 years after transplantation
      and are alive 3 and 4 years, respectively, later. Seven patients have had post
      transplant lymphoproliferative disease (PTLD) and 6 have had no recurrence for 3
      13 years after treatment. Impaired renal function with abnormal serum creatinine
      levels is increasingly common-11 patients have developed end stage renal failure,
      7 requiring renal transplantation, hypertension occurred in only 3 patients other
      than those in renal failure. Late rejection episodes associated with probable non
      adherence occurred in 7 patients. There were 10 late deaths; 2 from graft
      coronary disease; 1 from PTLD; 3 from renal failure; 3 from acute rejection and 1
      from infection. Conditional actuarial survival from 1 year post transplant was 76
      and 67% at 10 and 15 years, respectively. CONCLUSIONS: Survival for more than 10
      years is increasingly realistic. In this age group adherence and deteriorating
      renal function are major challenges.

PMID- 15848316
TI  - Living patches engineered from human umbilical cord derived fibroblasts and
      endothelial progenitor cells.
AB  - OBJECTIVE: A major shortcoming in contemporary congenital heart surgery is the
      lack of viable replacement materials with the capacity of growth and
      regeneration. Here we focused on living autologous patches engineered from human
      umbilical cord derived fibroblasts and endothelial progenitor cells (EPCs) as a
      ready-to-use cell source for paediatric cardiovascular tissue engineering.
      METHODS: EPCs were isolated from 20 ml fresh umbilical cord blood by density
      gradient centrifugation and myofibroblasts were harvested from umbilical cord
      tissue. Cells were differentiated and expanded in vitro using nutrient media
      containing growth factors. Before seeding, cell-phenotypes were assessed by
      immuno-histochemistry. Biodegradable patches fabricated from synthetic polymers
      (PGA/P4HB) were seeded with myofibroblasts followed by endothelialization with
      EPCs. All patches were cultured in a perfusion bioreactor. A subgroup of patches
      was additionally stimulated by cyclic strain. Analysis of the neo-tissues
      comprised histology, immuno-histochemistry, extracellular matrix (ECM) analysis
      and biomechanical testing. RESULTS: Endothelial phenotypes of EPCs before seeding
      were confirmed by Ac-Dil-LDL, CD 31, von-Willebrand-Factor and eNOS staining.
      Histology of the seeded patches demonstrated layered viable tissue formation in
      all samples. The cells in the newly formed tissues expressed myofibroblast
      markers, such as desmin and alpha-SMA. The EPCs derived neo-endothelia showed
      constant endothelial phenotypes (CD 31, vWF). major constituents of ECM such as
      collagen and proteoglycans were biochemically detected. Stress-strain properties
      of the patches showed features of native-analogous tissues. CONCLUSIONS: Living
      tissue engineered patches can be successfully generated from human umbilical cord
      derived myofibroblasts and EPCs. This new cell source may enable the tissue
      engineering of versatile, living, autologous replacement materials for congenital
      cardiac interventions.

PMID- 15848317
TI  - The RV-PA conduit stimulates better growth of the pulmonary arteries in
      hypoplastic left heart syndrome.
AB  - OBJECTIVE: This retrospective study compared the size of the central pulmonary
      arteries in patients with hypoplastic left heart syndrome (HLHS) following either
      a classical Norwood or Norwood procedure with a right ventricle to pulmonary
      artery (RV-PA) conduit. METHODS: Between May 2001 and May 2003, 30 patients with
      HLHS underwent cardiac catheterization prior to stage II palliation. Patients
      were initially palliated with a classical Norwood (Classical group, n=18) or
      Norwood procedure with RV-PA conduit (RV-PA group; n=12). Indexed maximum and
      minimum diameters of the LPA and RPA were measured using the McGoon ratio.
      Cardiac catheterisation was performed at a median age of 4.0 months. There was no
      difference in the time interval to catheterisation (P=0.13), Qp:Qs (P=0.41) or
      median haemoglobin (P=0.42) between the groups. RESULTS: The combined PA diameter
      was larger in the RV-PA group (B) than the classical group (A) (1.99+/-0.38
      versus 1.63+/-0.29, P<0.05). There were marked differences in the relative size
      of the pulmonary arteries between the two groups. In RV-PA patients, the LPA and
      RPA sizes were comparable (0.99+/-0.22 versus 1.00+/-0.31, P=1.00) whereas, in
      the classical group, the LPA was smaller than the RPA (0.75+/-0.15 versus 0.88+/
      0.17, P<0.05). Both techniques were also associated with discrete PA stenoses at
      the site of shunt insertion. Stenoses were more severe in RV-PA group (RV-PA),
      causing a 42+/-16% reduction in the combined PA diameter compared with a 28+/-18%
      reduction in Classical group (classical) (P<0.05). CONCLUSIONS: The Norwood
      procedure with RV-PA conduit is associated with better and more evenly
      distributed central pulmonary artery growth. Nevertheless, it is also associated
      with central PA stenoses, which may require subsequent reconstruction.

PMID- 15848318
TI  - Long-term outcome of right ventricular outflow tract reconstruction using a
      handmade tri-leaflet conduit.
AB  - OBJECTIVE: Since 1985, we have implanted handmade tri-leaflet conduits made of
      heterologous pericardium or expanded polytetrafluoroethylene (ePTFE), as an
      alternative to homograft for right ventricular outflow tract reconstruction. This
      report assesses the long-term outcome of these prostheses. METHODS: From 1985 to
      2003, 216 handmade tri-leaflet conduits were implanted in 191 patients. Forty-two
      patients had previous conduit repairs. The mean age at operation was 8.1+/-7.7
      years (range: 15 days-44 years). The underlying diagnoses were pulmonary atresia
      with ventricular septal defect in 83 patients, atrioventricular discordance in
      36, transposition of the great arteries in 26, double outlet right ventricle in
      14, and truncus arteriosus in 17. Whole heterologous pericardial tri-leaflet
      conduits were implanted in 169 patients, in the early series (porcine: 85;
      equine: 58; bovine: 26); bovine pericardial conduits containing ePTFE leaflets
      were implanted in 26 patients since 1996; whole ePTFE tri-leaflet rolls were
      employed in the most recent 21 patients. The conduit size was 21.1+/-3.1mm
      (range: 12-27 mm), 147.4+/-21.4% (range: 82.6-202.6%) of the anticipated diameter
      of the pulmonary valve. Follow-up was complete. RESULTS: There were 28 early
      deaths and 24 late deaths. The indication for conduit replacement was a peak
      instantaneous pressure gradient of greater than 50 mmHg. Sixty-five conduits
      required reoperation for conduit obstruction at 8.6+/-3.3 years after
      implantation. The freedom from reoperation at 5, 10, and 15 years was 93.9+/-1.9,
      61.4+/-4.5, and 35.5+/-5.6%, respectively. Patients with smaller conduit size and
      young age at operation were predisposed to reoperation. None of the 47 ePTFE tri
      leaflet conduits developed significant obstruction. The freedom from important
      pulmonary valve regurgitation (PR) as assessed by echocardiography was 68.3+/
      3.7% at 5 years, 33.0+/-4.5% at 10 years, and 21.6+/-4.9% at 15 years. No patient
      required reoperation due to PR or right ventricular dysfunction. CONCLUSIONS:
      Handmade tri-leaflet conduits provide a reliable alternative for RVOT
      reconstruction in children, yielding as good a long-term outcome as do
      homografts. Longer follow-up is needed to determine how well ePTFE leaflets will
      fare.

PMID- 15848319
TI  - Ascending-to-descending aortic bypass via right thoracotomy for complex (re-)
      coarctation and hypoplastic aortic arch.
AB  - OBJECTIVE: Operation for aortic recoarctation and/or residual hypoplastic arch
      represents a surgical challenge because of surrounding scar tissue in the
      coarctation area, hazard of spinal cord ischemia due to aortic cross-clamping,
      laceration of the recurrent nerve, and the choice of the best approach. We
      demonstrate the results of 52 operations of an extra anatomically bypass
      technique via right thoracotomy approach without establishment of cardiopulmonary
      bypass. METHODS: Since 1987, 52 patients underwent extra anatomically positioned
      ascending-descending bypass grafting. Indication was aortic recoarctation with
      concomitant hypoplastic aortic arch (45 patients), atypical coarctation of aortic
      arch (2 patients), congenital anomalies of aortic arch (2 patients) and
      concomitant aortic coarctation and associated cardiac problems that required
      surgical repair (2 patient), infected stent-graft of descending aorta (1
      patient). Mean age was 19.3 years. Systolic pressure gradients at rest ranged
      from 35 to 90mmHg; upper extremity hypertension was present in all patients.
      Operative technique consisted of performing aorta ascending-descending bypass
      graft size 16 or 18mm in diameter, via right thoracotomy (in 51 patient) or
      sternotomy (in 1 patient). RESULTS: The mortality rate was 1.9% (1/52). Five
      patients returned to the operating room (in 3-5 days after operation) for a
      lymphorrhea complication. An arterial pressure gradient in the limbs was totally
      corrected. During a follow-up period of actually 79+/-54 months, no adverse event
      was noticed and antihypertensive medication was stopped in all patients.
      CONCLUSIONS: Ascending-to-descending aortic bypass via right thoracotomy is a
      safe and effective method for management complex (re-) coarctation and
      hypoplastic aortic arch.

PMID- 15848320
TI  - Arch-first technique performed under hypothermic circulatory arrest with
      retrograde cerebral perfusion improves neurological outcomes for total arch
      replacement.
AB  - OBJECTIVE: From 1998, we have adopted the arch first technique (reconstruction of
      arch vessels first and distal anastomosis second) instead of the distal
      anastomosis first technique for total arch replacement. The aim is to reduce the
      period of deep hypothermic circulatory arrest and the retrograde cerebral
      perfusion time. We evaluate the surgical results of the arch first technique.
      METHODS: The arch first technique was used in 50 cases (38 male and 12 female),
      of average age 68 years, from 1998 to 2003. There were 33 true aneurysms and 10
      chronic and seven acute type A dissections. Clinical results were evaluated and
      compared with the distal first technique used in 24 cases operated on between
      1992 and 1998. These were 14 males and 10 females, with an average age of 68
      years. There were 16 true aneurysms, and three chronic and five acute aortic
      dissections. RESULTS: For the arch first technique there is a significantly
      shorter circulatory arrest time (32 vs. 72min, P<0.0001), but similar body
      ischemic times (76 vs. 72min, N.S.). With the arch first technique, all but two
      patients awoke within 24h, with an average delay of 9.3h. In the distal first
      technique, two patients did not awaken and three patients showed delayed
      awakening, with an average awakening time of 24h. The arch first technique led to
      one hospital death (2%), due to residual aneurysm rupture. Reversible ischemic
      neurological deficit (RIND) was complicated in three cases (6%), but no stroke
      occurred during operation. In the distal first technique there were four strokes,
      one RIND and three hospital deaths (12.5%). The arch first technique gave a
      significantly lower intra-operative stroke rate (P=0.0030) and smaller hospital
      mortality (P=0.0615). The arch first technique led to five late deaths, with an
      84.5% 3 year survival rate, and the distal first technique led to six late deaths
      with a 59.1% 3-year survival rate. CONCLUSIONS: The arch first technique is
      clearly superior to the conventional distal first technique in surgical mortality
      and morbidity regarding neurological outcome, and provides a higher survival rate
      and better quality of life. The arch first technique is an excellent method for
      total arch replacement.

PMID- 15848321
TI  - Treatment of type B aortic dissection: endoluminal repair or conventional medical
      therapy?
AB  - OBJECTIVE: To evaluate the mid-term results of endovascular stent-grafting for
      type B aortic dissection, in comparison with those of standard medical therapy in
      uncomplicated cases. METHODS: Between January 1999 and 2004, among 56 patients
      (mean age 59.5+/-11.5 years) with type B aortic dissection, hypotensive medical
      therapy was the only treatment in 28 uncomplicated cases, (group A), while stent
      graft implantation was performed in 28 patients with uncontrolled hypertension,
      persistent pain or evidence of dissection progression or complication (group B).
      In 14 cases (50%) the procedure was performed in an acute setting. Stent-grafting
      procedures were monitored with intraoperative trans-esophageal echocardiography
      and cine-angiography. CT scan and trans-esophageal echocardiography were
      performed before hospital discharge, at 6 and 12 months and then yearly. RESULTS:
      Follow-up (range 1-61 months, average 18.1+/-16.9 months) was 100% complete. In
      hospital mortality was 10.7% (three patients, all belonging to Group B; P=0.24).
      No spinal cord injuries were observed. Early endoleak occurred in one patient
      (3.5%). Mid-term mortality was lower in Group B, although the difference was not
      significant (10.7 versus 14.3% in Group A, P=0.71). Follow-up CT scans evidenced
      complete thrombosis of the false lumen in 75% cases in Group B, 10.7% in Group A
      (P=0.0001), and an aneurismal dilatation of the descending aorta in 3.5% cases in
      Group B, 28.5% in Group A (P=0.02). CONCLUSIONS: Although with still considerable
      early mortality, endovascular stent-graft implantation is an effective option for
      the treatment of complicated type B aortic dissection. Endovascular treatment
      achieved a better mid-term fate of the descending thoracic aorta than medical
      therapy alone, even in patients with worse preoperative conditions.

PMID- 15848322
TI  - A normogram to anticipate dimension of neo-sinuses of valsalva in valve-sparing
      aortic operations.
AB  - OBJECTIVE: The aim of the present study was to define a method to pre-determine
      the correct size of neo-sinuses of Valsalva in the reimplantation type of valve
      sparing aortic operation. METHODS: The objective was achieved in three steps: (1)
      evaluation in the healthy population, of the normal size of sinuses of Valsalva
      expressed as the area surrounding fully opened aortic cusps, the so-called beyond
      leaflets area; (2) elaboration of a normogram by which, given a known annular
      diameter, it is possible to select the appropriate graft size to obtain a normal
      beyond leaflets area; (3) validation of the normogram by comparing, in a
      population of 20 patients undergoing a valve-sparing procedure, the predicted and
      observed beyond leaflets area. RESULTS: The following values for beyond leaflets
      area were observed: mean normal 320.6+/-120.6mm(2), mean predicted 355+/
      63.2mm(2), mean observed 364.7+/-72.8mm(2).No significant differences were
      obtained for predicted versus observed values. Regression analysis showed a
      linear distribution with an r value of 0.95. CONCLUSIONS: We proposed a
      simplified approach for sizing of the neo-aortic root in the reimplantation type
      of valve-sparing aortic operation focussed on the size of sinuses of Valsalva.
      Our normogram showed to be reliable in anticipating beyond leaflets area. It can
      be helpful in avoiding the selection of an undersized or excessively oversized
      graft.

PMID- 15848323
TI  - Percutaneous aortic valve replacement: resection before implantation.
AB  - OBJECTIVE: After transluminal endovascular implantation of a new valved stent,
      the aim of this study was to evaluate the feasibility of using a high-pressure
      water stream to endovascularly resect human calcified aortic valves. METHODS:
      First, human calcified aortic valves were excised and then resected in vitro to
      determine optimal water jet parameters. Second, healthy porcine aortic valves
      were ablated in vitro to evaluate possible destruction to the surrounding
      anatomy. Third, resection was performed endoluminally by introducing
      microsystemic tools into the descending aorta, passing them through the arch and
      ascending aorta to the aortic valve in an in vitro porcine model. Macro- and
      micropathology of specimens were analyzed. RESULTS: First, resection of human
      calcified valves took a mean of 6.0+/-2.4min per three leaflets at 150bar (n=17).
      The maximum size of the cut leaflets was 7.1+/-1.7mm. Second, resection of
      healthy porcine aortic valves at 60bar took 2.3+/-0.3min per three leaflets
      (n=10). Only the aortic annulus was moderately affected in six cases. Third,
      endoluminal resection via the descending aorta took 12.2+/-0.8min per three
      leaflets at 60bar (n=10). The aortic wall was affected in four cases, the aortic
      annulus and the coronary ostia only once. Microscopic analysis also revealed
      superficial lesions with a maximum lesion depth of 1200microm in one case, and an
      average of 580+/-145microm in subsequent lesions. The mitral valve and the left
      ventricular outflow tract were not affected. CONCLUSIONS: Percutaneous resection
      of heart valves is emerging as a promising auxiliary method for the resection of
      calcified aortic heart valves because they can be cut endoscopically.
      Nonetheless, before this resection tool can be clinically applied by surgeons to
      perform a true percutaneous valve replacement, an additional aortic valve
      resection chamber (already at the prototype stage) designed for capturing all
      debris, has to be established.

PMID- 15848324
TI  - Concomitant anti-arrhythmic procedures to treat permanent atrial fibrillation in
      CABG and AVR patients are as effective as in mitral valve patients.
AB  - OBJECTIVE: Concomitant anti-arrhythmic procedures, to treat permanent atrial
      fibrillation, are not routinely performed in non-mitral valve surgery, such as
      coronary artery bypass grafting (CABG) and aortic valve (AVR) procedures. This
      study evaluated the sinus rhythm (SR) conversion rate of a concomitant anti
      arrhythmia procedure in non-mitral valve surgery compared to mitral valve
      surgery. METHODS: Between 1997 and 2003, 128 patients with a documented permanent
      atrial fibrillation had a concomitant anti-arrhythmic procedure using unipolar
      endocardial radiofrequency ablation; 65 mitral valve surgery (group I) and 63
      aortic valve surgery or CABG (group II). Follow-up was complete and included
      standard ECG and echocardiogram at 3, 6, 12 months and each consecutive year.
      Stability of SR was confirmed with a 24-h ECG registration. RESULTS: Type of
      procedures was MVR 42 (32.8%), MVP 23 (18.0%), CABG 40 (31.2), AVR 21 (16.4%),
      other 2 (1.6%). Thirty-day mortality for groups I and II were 4.6% (3/65) and
      3.2% (2/63). Group II patients were distinctly older (69.3 versus 64.8 years;
      P=0.04), but the size of the left atrium was smaller (45.9 versus 52.4mm;
      P=0.0001) and the aortic cross-clamp time was shorter (91 versus 99min; P=0.05).
      The cumulative postoperative SR percentages for the groups I and II patients at
      12 months were 71 versus 79%. A bi-atrial contraction was observed in 65.6%
      (21/32) and 68.3% (28/41) of the groups I and II patients, who had a stable SR.
      The mean (SD) follow-up for groups I and II was 24.4 (19.4) and 21.0 (17.2)
      months. The cumulative survival rate at 1, 2 and 3 years for groups I and II were
      85 versus 88%, 83 versus 85%, 79 versus 85% (log-rank test P=0.60). CONCLUSION: A
      concomitant anti-arrhythmic procedure in CABG and AVR patients is as effective as
      in mitral valve patients, although these patients tend to be older, but with a
      smaller left atrial size.

PMID- 15848325
TI  - Preoperative left ventricular dimensions predict reverse remodeling following
      restrictive mitral annuloplasty in ischemic mitral regurgitation.
AB  - OBJECTIVE: Ischemic mitral regurgitation can be treated with a restrictive mitral
      annuloplasty, with or without coronary revascularization. In this study, the
      extent of reverse remodeling of the left ventricle following this strategy is
      assessed, as well as the factors that influence it. METHODS: Eighty-seven
      consecutive patients with ischemic mitral regurgitation and a mean ejection
      fraction of 32+/-10% underwent restrictive mitral annuloplasty (downsizing by two
      ring sizes, median ring size 26), with additional coronary revascularization in
      75 patients. All underwent transthoracic echocardiography 18 months after surgery
      to assess residual mitral regurgitation, mitral valve gradient and left
      ventricular end-systolic and end-diastolic dimensions. Univariate and
      multivariate analysis was performed to identify predictors for reverse
      remodeling, defined as a 10% reduction in left ventricular dimension. Receiver
      operating characteristic analysis was used to identify cut-off values for
      preoperative left ventricular dimensions in predicting reverse remodeling.
      RESULTS: Early mortality was 8.0% (seven patients, three non-cardiac), late
      mortality was 7.5% (six patients, four non-cardiac). There were two reoperations
      (redo annuloplasty), and four readmissions for heart failure. At 29 months follow
      up, NYHA class improved from 3.0+/-0.9 to 1.3+/-0.5 (P<0.01). Mitral
      regurgitation grade decreased from 3.1+/-0.5 to 0.6+/-0.6 at 18 months, left
      ventricular end-systolic dimension decreased from 52+/-8 to 44+/-11 mm (P<0.01),
      and end-diastolic dimension from 64+/-8 to 58+/-10mm (P<0.01). Multivariate
      analysis identified preoperative left ventricular end-diastolic dimension as the
      single best factor in predicting occurrence of reverse remodeling. For end
      systolic dimension, 51mm was the optimal cut-off value to predict reverse
      remodeling (specificity and sensitivity 81%, area under curve 0.85); for end
      diastolic dimension, the cut-off value was 65mm (specificity and sensitivity 89%,
      area under curve 0.92). CONCLUSIONS: Stringent restrictive mitral annuloplasty
      with or without revascularization provides excellent clinical results with
      acceptable mortality. At 18 months follow-up, there is no significant residual
      mitral regurgitation. Reverse remodeling occurs in the majority of patients, but
      is limited by preoperative left ventricular dimensions. In patients with a left
      ventricular end-diastolic dimension exceeding 65mm, additional surgical
      procedures are necessary to try and obtain reverse remodeling in this subgroup.

PMID- 15848326
TI  - Triflusal versus oral anticoagulation for primary prevention of thromboembolism
      after bioprosthetic valve replacement (trac): prospective, randomized, co
      operative trial.
AB  - OBJECTIVE: Antiplatelet agents are used for prevention of thromboembolism in
      surgical patients and in patients with chronic atrial fibrillation. Up to date,
      however, results of randomized studies comparing antiplatelet agents and oral
      anticoagulation have not been reported. The aim of this study was to compare the
      efficacy and safety of triflusal (an antiplatelet agent) versus acenocoumarol for
      primary prevention of thromboembolism in the early postoperative period after
      implantation of a bioprosthesis. METHODS: In this prospective, multicentric,
      randomized, open pilot trial, patients were assigned to treatment with triflusal
      (600mg/d) or acenocoumarol (target INR 2.0-3.0). Study medication was started 24
      48h after valve replacement with a bioprosthesis, and continued for 3 months.
      Four follow-up visits were scheduled: baseline, and at 1, 3 and 6 months
      thereafter. The primary end-point was a composite of the rate of thromboembolism,
      severe hemorrhage and valve-related mortality. RESULTS: A total of 193 patients
      were included (97 received triflusal and 96 acenocoumarol), with a mean age of
      72.5 years. Half were men. Aortic valve replacement was performed in 181 patients
      (93.8%), mitral valve replacement in 10 patients (5.2%) and double valve
      replacement in 2 (1.0%). Hospital mortality was 11 (5.7%). Primary outcome was
      recorded in 9 patients with triflusal (9.4%) and in 10 patients with
      acenocoumarol (11%). There were nine episodes (4.7%) of thromboembolism, six in
      the triflusal group and three in the acenocoumarol group, and three episodes of
      permanent neurological deficits, one in the triflusal group and two in the
      acenocoumarol group. Severe hemorrhage: nine episodes, six in the acenocoumarol
      group and three in the triflusal group. None of the observed differences in
      efficacy were statistically significant. Regarding safety, three patients in
      triflusal group reported at least one hemorrhage, compared to 10 in acenocoumarol
      group (P=0.048). CONCLUSIONS: There were no significant differences in efficacy
      between both groups, however, triflusal showed a significantly lower incidence of
      bleeding episodes.

PMID- 15848327
TI  - Risk stratification with cardiac troponin I in patients undergoing elective
      coronary artery bypass surgery.
AB  - OBJECTIVE: Cardiac troponin I (cTnI) is a highly sensitive and specific marker
      for postoperative prediction of patients outcome after coronary artery bypass
      surgery (CABG). Whether preoperatively elevated cTnI levels similarly predict the
      outcome in patients scheduled for elective CABG is currently unknown. METHODS:
      Therefore, a possible correlation between preoperative cTnI levels and
      perioperative major adverse events and in-hospital mortality after CABG was
      investigated. CTnI was measured within 24h before surgery in 1405 out of 3124
      consecutive elective CABG patients. Out of these patients, 1178 had a
      preoperative cTnI level below 0.1ng/ml (group 1), 163 patients had a cTnI level
      between 0.11 and 1.5ng/ml (group 2), and 64 patients had a cTnI level above
      1.5ng/ml (group 3). CTnI levels, electrocardiograms, clinical data, adverse
      events and in-hospital mortality were recorded prospectively. Patients with ST
      elevation myocardial infarction less than 7 days before surgery were excluded
      from the study. RESULTS: Perioperative myocardial infarction (PMI) occurred in
      69/1178 patients (5.9%) in group 1, 14/163 patients (8.6%; odds ratio (OR) 1.5,
      95% confidence interval (CI): 0.8-2.8) in group 2, and 11/64 patients (17.2%; OR
      3.3, CI: 1.6-7.0) in group 3 (overall: P<0.001, Cochran-Armitage trend test). Low
      cardiac output syndrome (LCOS) occurred in 19/1178 patients (1.6%), 9/163 (5.5%;
      OR 3.6, CI: 1.5-8.5), and 7/64 patients (10.9%; OR 7.5, CI: 2.7-19.8) (overall:
      P<0.001, group 1 vs. group 2: P<0.002), respectively. In-hospital mortality was
      1.7% in group 1 and 3.1% in group 2, but 6.3% (OR 3.9, CI: 1.1-12.5) in group 3
      (overall: P<0.01, group 1 vs. group 2: P=NS). Intensive care and hospital stay
      were significantly longer in group 3 compared to groups 1 and 2. Univariate and
      multivariate logistic regression analysis confirmed the statistically significant
      relationship between cTnI and PMI, LCOS and in-hospital mortality, respectively
      (P<0.001). CONCLUSIONS: Risk stratification by measurement of cTnI levels within
      24h before elective CABG clearly identifies a subgroup of patients with increased
      risk for postoperative adverse outcome and in-hospital mortality.

PMID- 15848328
TI  - Has the in situ right internal thoracic artery been overlooked? An angiographic
      study of the radial artery, internal thoracic arteries and saphenous vein graft
      patencies in symptomatic patients.
AB  - OBJECTIVE: The right internal thoracic artery is being used infrequently despite
      favorable observational angiographic data. Conversely, the radial artery
      utilization has increased with only limited data available. The purpose of this
      paper is to re-evaluate the roles of the right internal thoracic artery and the
      radial artery grafts. METHODS: We reviewed all ischemia-directed coronary
      angiographic procedures from January 1996 to December 2003. A total of 219
      patients had primary coronary artery bypass grafting with an internal thoracic
      artery and a radial artery as two of the bypass grafts. Six hundred and seventy
      nine (679) graft angiograms (45 saphenous vein, 363 radial artery, 54 right
      internal thoracic artery and 217 left internal thoracic artery) were studied. The
      mean period from operation to re-angiogram was 1104+/-761 days. Angiographic
      outcomes were divided into groups as: (1) patent (<50% stenosis) or (2) failed
      (>or=50% stenosis, string sign or occluded). A generalized linear mixed model was
      used to analyze predictors of graft patency. Turnbull's estimates of cumulative
      patency were used to compare graft failure rates over time. RESULTS: A total of
      632/679 (93%) grafts were patent and 47/679 (7%) grafts had failed. Empirical
      saphenous vein graft patency was 40/45 (89%), radial artery patency 329/363
      (91%), right internal thoracic artery patency 51/54 (94%) and left internal
      thoracic artery patency 212/217 (98%). Pairwise comparisons of patency from the
      generalized linear mixed model were: LITA>RITA, OR=1.5 (P=0.5); LITA>RA, OR=5.7
      (P<0.001); LITA>SV, OR=6.5 (P<0.001); RITA>RA, OR=3.9 (P=0.01); RITA>SV, OR=4.4
      (P=0.01); RA>SV, OR=1.1 (P=0.7). Five-year patency estimates from the Turnbull's
      model were the left internal thoracic artery (95.9%), right internal thoracic
      artery (91.2%), the radial artery (90.6%) and the saphenous vein (81.8%).
      CONCLUSIONS: Consideration should be given to the routine use of both internal
      thoracic arteries for coronary artery bypass grafting. When additional grafts are
      required, there is no evidence to suggest that either the radial artery or
      saphenous vein is superior.

PMID- 15848329
TI  - First clinical results with a 30 degrees end-to-side coronary anastomosis
      coupler.
AB  - OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of a
      novel 30 degrees end-to-side coronary anastomotic coupler (Converge Medical,
      Inc., Sunnyvale, CA) that facilitates a non-penetrating, sutureless vein graft to
      coronary artery anastomosis. MATERIAL AND METHODS: The Coupler utilizes a set of
      concentric mating frames approximating adjacent vessel tissue allowing for
      biological healing of the anastomosis. The frames are manufactured from Nitinol,
      a nickel titanium super-elastic metal alloy. The Nitinol frames attach the bypass
      graft to the coronary artery in a 30 degrees end-to-side configuration. Between
      November 2002 and March 2003 a total of 46 patients (44 male) with a mean age of
      63.6+/-7.5 years were admitted for coronary artery revascularization and included
      in the study. The mean LVEF was 60.6+/-12.4%. RESULTS: Thirty-three patients were
      successfully treated with the Coupler. Nine patients did not meet the
      intraoperative inclusion criteria, and were excluded from the study due to small
      (<or=2.0mm) or severely calcified coronary vessels, or small vein grafts.
      Hemostasis could not be achieved with the Coupler in 3 patients, and in one
      patient the graft flow measured intraoperative was low. In these instances the
      Coupler was removed and the anastomosis was sutured without complication. Average
      mean flow rate using transit time method through the Coupler attached bypasses
      was 54+/-26ml/min. In a control angiography 2 months after surgery, 29 (96.7%) of
      the 30 connector grafts were patent. One stenosis of 50% occurred on the site of
      a connector anastomosis. Angiographic patency assessments for 81 hand sewn grafts
      revealed 73 (90.1%) patent grafts. CONCLUSION: Initial results indicate that the
      Converge Coupler can be used to create a safe and effective 30 degrees vein graft
      to coronary artery anastomosis under suitable conditions.

PMID- 15848330
TI  - Health related quality of life after percutaneous coronary intervention versus
      coronary artery bypass graft surgery in patients with acute coronary syndromes
      without ST-segment elevation. 12-month follow up.
AB  - OBJECTIVE: The efficacy of percutaneous and surgical revascularization in acute
      coronary syndromes without ST-segment elevation is similar. Therefore, other
      factors, like health-related quality of life, should play an important role in
      choosing the revascularization method. METHODS: We compared 12-month health
      related quality of life for high-risk patients with acute coronary syndromes
      without ST-segment elevation assigned to percutaneous coronary intervention
      (group A) versus coronary artery bypass graft surgery (group B). Patients had an
      episode of rest angina within 24h prior to admission and had to fulfil at least
      one of the criteria: (1) ST-segment depression (>or=0.05mV), (2) transient
      (<20min) ST-segment elevation or T-wave inversion (>or=0.1mV), (3) positive serum
      cardiac markers. Four hundred and ninety-six (91.34%) of 543 patients alive 12
      months after index hospitalization completed a Short Form-36 (SF-36) health
      status survey. Group A comprised 392 patients and group B comprised 104 patients.
      We compared mental component summary (MCS) and physical component summary (PCS)
      scores from the SF-36 survey between analyzed groups. RESULTS: There were no
      significant differences in MCS scores (47.21+/-12.30 vs. 46.60+/-11.3 in group A
      and group B, respectively, NS). PCS scores were lower in group A (38.30+/-11.10
      vs. 42.64+/-9.76; p=0.003). Patients of group A had a higher rate of unstable
      angina (22.45 vs. 5.77%, p=0.0002) and repeated revascularization (12.76 vs.
      1.92%, p=0.001) at 1 year. Patients of group A also had higher systolic and
      diastolic blood pressure during follow-up (138.17+/-20.41 vs. 133.47+/-19.21,
      p=0.04 and 82.48+/-11.32 vs. 77.25+/-16.17, p=0.0003, respectively). Systolic
      blood pressure was inversely associated with PCS scores in group A (Spearman's R=
      -0.18 p=0.0007). CONCLUSIONS: This study has shown that there is a significant
      difference in health-related quality of life 12-months after percutaneous
      coronary intervention and coronary artery bypass graft surgery. This difference
      arises from better physical function (physical component summary) for coronary
      artery bypass graft surgery patients compared with percutaneous coronary
      intervention patients. Despite impairment of the physical health status (physical
      component summary), the mental health status (mental component summary) remained
      similar in both groups.

PMID- 15848331
TI  - Timing of intra-aortic balloon pump support and 1-year survival.
AB  - OBJECTIVE: The relationship between the timing of intra-aortic balloon pump
      (IABP) support and surgical outcome remains a subject of debate. Peri-operative
      mechanical circulatory support is commenced either prophylactically or after
      increasing inotropic support has proved inadequate. This study evaluates the
      effect timing of IABP support on the 1-year survival of patients undergoing
      cardiac surgery. METHODS: From April 1997 to September 2002, 7698 consecutive
      cardiac surgical procedures were performed. This included 5678 isolated coronary
      artery bypasses (CABGs), 1245 isolated valve procedures and 775 simultaneous CABG
      and valve procedures. IABP support was required in 237 patients (3.1%). Twenty
      seven patients (0.35%) were classed as high-risk and received preoperative IABP
      support, 25 patients (0.32%) were haemodynamically compromised and required
      preoperative IABP support, 120 patients (1.56%) required intra-operative IABP
      support, and 65 patients (0.84%) required post-operative IABP support. Multiple
      variables were offered to a Cox proportional hazards model and significant
      predictors of 1-year survival were identified. These were used to risk adjust
      Kaplan-Meier survival curves. RESULTS: 1-year follow-up was complete and 450
      deaths (5.8%) were recorded. The significant independent predictors of increased
      mortality at 1-year (P<0.05, HR=hazard ratio) were post-operative renal failure
      (HR=3.5), increasing EuroSCORE (HR=1.2), post-operative myocardial infarction
      (HR=3.7), post-operative IABP (HR=4.1) intra-operative IABP (HR=2.8), post
      operative stroke (HR=2.5), increasing number of valves (HR=1.6), ejection
      fraction <30% (HR=1.3) and triple-vessel disease (HR=1.3). After risk-adjustment,
      1-year survival for patients who required intra-operative IABP support was
      significantly greater than for those patients who required IABP support in the
      post-operative period. CONCLUSIONS: Patients who warrant IABP support in the post
      operative setting have a significantly increased mortality at 1-year when
      compared to any other group. Therefore, earlier IABP support as part of surgical
      strategy may help to improve the outcome.

PMID- 15848332
TI  - Evaluation of Cystatin C as a marker of renal injury following on-pump and off
      pump coronary surgery.
AB  - OBJECTIVE: Cardiopulmonary bypass is regarded as an important contributor to
      renal injury, whereas off-pump surgery is considered less damaging. Cystatin C, a
      cystine protease inhibitor, is more sensitive and specific than creatinine in the
      assessment of renal function. We assessed the value of Cystatin C in quantifying
      clinical and subclinical renal injury following on-pump and off-pump cardiac
      surgery. METHODS: Sixty consecutive patients were recruited: 30 patients
      undergoing on-pump CABG and 30 patients undergoing off-pump CABG. Blood samples
      were collected pre-operatively and on days 1, 2 and 4 postoperatively to measure
      serum creatinine and serum Cystatin C. Urinary samples were collected
      concurrently to measure microalbumin and N-acetyl-beta-glucosaminidase, denoting
      changes in renal glomerular and tubular function respectively. RESULTS: The off
      pump group were older (65+/-11 vs. 61+/-8 years; P=0.046), had a higher mean
      Parsonnet score (9.4+/-6.2 vs. 5.4+/-3.6, P<0.01) and received fewer grafts
      (2.4+/-0.9 vs. 3.1+/-0.7; P<0.01) compared to the on-pump group. The groups were
      otherwise matched with respect to preoperative renal function and left
      ventricular function. Patients undergoing on-pump CABG had greater increases in
      all four parameters of renal injury. Adjustment for preoperative differences
      increased the size and significance of the effect of off-pump vs. on-pump surgery
      (percent difference 13%; 95% CI 2-26 for creatinine, and 16%; 95% CI 4-29 for
      Cystatin C). Cystatin and creatinine were strongly correlated with each other.
      CONCLUSIONS: Avoidance of cardiopulmonary bypass may reduce renal injury
      particularly in higher risk patients. Cystatin C proved to be a simple and
      sensitive measure of overall renal function and can be used in the routine
      assessment of renoprotective strategies.

PMID- 15848333
TI  - Natriuretic peptides and E-selectin as predictors of acute deterioration in
      patients with inotrope-dependent heart failure.
AB  - OBJECTIVE: In patients with inotrope-dependent end-stage heart failure the timely
      application of the most suitable treatment, i.e. heart transplantation,
      implantation of a ventricular assist device or conservative treatment, is a key
      issue for therapeutic success. METHODS: Seventy-six inotrope-dependent patients
      with end-stage heart failure were enrolled. Measurements of hemodynamics, routine
      laboratory parameters, and clinical examination were performed daily.
      Additionally, natriuretic peptides (BNP and NT-proBNP) and E-selectin were
      measured at the end of the study. The patients were retrospectively divided into
      groups with regard to the following end-points: Group I-deterioration into
      cardiogenic shock after an initially stable clinical course (n=26); Group II
      stable clinical course without deterioration into cardiogenic (n=41); Group III
      weaning from inotropic support (n=9). RESULTS: One day before cardiogenic shock
      occurred, BNP, NT-proBNP and E-selectin were significantly elevated in group I
      compared with group II. A logistic regression model showed that only BNP and E
      selectin were independent predictors of clinical deterioration on the following
      day. The odds ratio (OR) for E-selectin using a cut-off point of 65ng/ml was 8.7
      and for BNP using a cut-off of 500pg/ml it was 4.8. In combination, the OR
      increased to 11.1. Continuous decrease of NT-proBNP predicted patients in whom
      weaning from inotropes was possible. CONCLUSIONS: While routine parameters did
      not predict the clinical course, elevated BNP and E-selectin independently
      predicted cardiogenic shock on admission and 1 day before its occurrence. The
      combination showed increased predictive value.

PMID- 15848335
TI  - A high fidelity tissue-based cardiac surgical simulator.
AB  - OBJECTIVE: Issues concerning the training and certification of surgical
      specialists have taken on great significance in the last decade. A realistic
      computer-assisted, tissue-based simulator developed for use in the training of
      cardiac surgical residents in the conduct of a variety of cardiac surgical
      procedures in a low-volume cardiothoracic surgery unit of a typical developing
      country is described. The simulator can also be used to demonstrate the function
      of technology specific to cardiac surgical procedures in a way that previously
      has only been possible via the conduct of a procedure on a live animal or human
      being. METHODS: A porcine heart in a novel simulated operating theatre
      environment with real-time simulated haemodynamic monitoring and coronary blood
      flow, in arrested and beating-heart modes, is used as a training tool for
      surgical residents. RESULTS: Standard and beating-heart coronary arterial bypass,
      aortic valve replacement, aortic homograft replacement and pulmonary autograft
      procedures can be simulated with high degrees of realism and with the
      superimposition of adverse clinical scenarios requiring valid decision making and
      clinical judgments to be made by the trainees. CONCLUSIONS: The cardiac surgical
      simulation preparation described here would appear to be able to contribute
      positively to the training of residents in low-volume centres, as well as having
      the potential for application in other settings as a training tool or clinical
      skills assessment or accreditation device. Collaboration with larger centres is
      recommended in order to accurately assess the utility of this preparation as an
      adjunctive cardiothoracic surgical training aid.

PMID- 15848334
TI  - Long and short-term outcomes in patients requiring continuous renal replacement
      therapy post cardiopulmonary bypass.
AB  - OBJECTIVE: The development of acute renal failure following cardiac surgery is a
      rare but devastating complication with high morbidity and mortality. This study
      aimed to assess the incidence of acute renal failure necessitating continuous
      renal replacement therapy (CRRT) in patients who required cardiopulmonary bypass,
      to determine the factors associated with mortality and to evaluate long-term
      outcome. METHODS: Patients who underwent cardiac surgery between October 1997 and
      2003 and treated with CRRT were included (n=98). Six patients were then excluded
      (already in established renal failure pre-operatively) and one patient lost to
      follow-up. A retrospective analysis was carried out. RESULTS: Overall CRRT was
      used in 2.9% (92/3172). The mean (SD) age of patients was 68 (10) years. Their
      mean pre-operative creatinine level and duration of cardiopulmonary bypass were
      154 (87)micromol/l and 160 (84)min, respectively. Mean duration from surgery to
      establishment of CRRT was 50 (42)h. Mean creatinine level prior to hospital
      discharge was 168 (93)micromol/l. Thirty-day mortality was 42%. Significant risk
      factors for death were complex procedures (odds ratio=9.9), gastro-intestinal
      complications (OR=7.2), cross-clamp time over 88min (OR=5.9), re-exploration
      (OR=4.0) and patients age over 75 years (OR=3.3). Actuarial 1 and 5-year
      survivals (95% CI) were 53 (43, 63) % and 52 (42, 62) %, respectively. Only 2
      (2.2%) patients required long term renal support. CONCLUSIONS: Acute renal
      failure necessitating the use of CRRT is a rare but serious complication post
      cardiopulmonary bypass. In the long-term, surviving patients are not likely to
      require further renal support.

PMID- 15848336
TI  - Virtual angioscopy from multi-detector row computed tomography for an anastomotic
      aneurysm.

PMID- 15848337
TI  - Diagnosis of anomalous origin of the circumflex artery by multidetector CT.

PMID- 15848338
TI  - Intimal sarcoma of pulmonary artery: multi-slice ECG-gated computed tomography
      findings with 3D reconstruction.

PMID- 15848339
TI  - Simultaneous double video mediastinoscopy and video mediastinotomy--a step
      forward.
AB  - Mediastinal lymph node biopsy plays a fundamental role in diagnosis, staging and
      management of lung cancer. We describe a novel method of using the video
      mediastinoscope for concurrent cervical mediastinotomy and anterior
      mediastinoscopy. We have performed five concurrent procedures using this system
      in the last 14 months. In four cases, we assessed the aorto-pulmonary (A-P)
      window lymph nodes. In the fifth case, we performed a cervical mediastinoscopy
      for para-tracheal and sub-carinal lymphadenopathy followed by an anterior
      videomediastinotomy, video assisted intrapericardial assessment, direct tumour
      sampling and A-P window lymph nodal biopsies. Due to the excellent visualisation
      afforded by the Videomediastinoscope, we were able to avoid an open procedure in
      all cases. We believe that this represents a major benefit of the
      videomediastinoscope in select cases.

PMID- 15848340
TI  - Reversed-J inferior sternotomy for awake coronary bypass.
AB  - Many approaches for minimally invasive coronary bypass surgery are available and
      to further decrease the invasiveness, coronary artery bypass grafting has been
      performed under high thoracic epidural anesthesia without endotracheal intubation
      in the last years. Less invasive approach to coronary artery bypass graft
      operations is possible through combination of the high thoracic epidural
      anesthesia and a reversed-J sternotomy, and coronary revascularization can be
      accomplished without any additional technical difficulties and with a good
      exposure of both the left anterior descending artery and the left internal
      thoracic artery. This technique is less traumatic for patients and provides
      practical better oxygenation and shorter hospital stay.

PMID- 15848341
TI  - A simple method to adapt the height of the sinotubular junction of the De Paulis
      Valsalva graft to the height of the patient's sinuses in David reimplantation
      procedure.
AB  - De Paulis and associated introduced a new aortic root conduit for valve-sparing
      operation. The use of this prosthesis for David I (reimplantation) procedure
      occasionally may be problematic when the top of the commissures, do not match the
      new sinotubular junction of the graft. We propose a simple method that allows to
      create a new sinotubular junction at the desired level in the skirt portion of
      the Valsalva prosthesis.

PMID- 15848342
TI  - Reconstruction of left main coronary artery with subclavian artery free graft in
      an infant.
AB  - We report the case of a 3-month-old infant with anomalous origin of the left
      coronary artery from the pulmonary artery (ALCAPA) with absent left main coronary
      artery (LMCA). She underwent repair by reimplantation technique with the
      construction of a short LMCA using two opposite flaps. Two months later she was
      re-admitted in cardiac failure. Occlusion of the reconstructed LMCA was found by
      angiogram. At reoperation the right subclavian artery was used as a free
      interposition graft to reconstruct the LMCA. The post-operative course was
      uneventful. At 8 months she was asymptomatic and LMCA patency was demonstrated by
      angiogram.

PMID- 15848344
TI  - OPCAB and the incidence of atrial fibrillation: ignoring the current best
      available evidence.

PMID- 15848345
TI  - Choice of mechanical support for fulminant myocarditis: ECMO vs. VAD?

PMID- 15848346
TI  - Clinical and morphologic evidence points to closure of the zone of apposition in
      atrioventricular septal defects.

PMID- 15848348
TI  - Edge-to-edge technique for correction of tricuspid valve regurgitation due to
      complex lesions.

PMID- 15848351
TI  - An alternative to drain clamping for blood pleurodesis.

PMID- 15848353
TI  - Intraabdominal and postoperative peritoneal adhesions.

PMID- 15848354
TI  - Etiology and treatment of varicose ulcer of the leg.

PMID- 15848355
TI  - Changes in the management of injuries to the liver and spleen.

PMID- 15848356
TI  - Impact of work-hour restrictions on residents' operative volume on a subspecialty
      surgical service.
AB  - BACKGROUND: Whether the 80 hours per week limit on surgical residents' work hours
      has reduced the number or variety of cases performed by residents is unknown.
      STUDY DESIGN: We quantified residents' operative experience, by case category, on
      a pediatric surgical service. The number of senior and junior residents' cases
      were compared between residents from the year before (n = 47) and after (n = 44)
      the 80-hour limit. Residents also completed a questionnaire about their operative
      and educational experience. As an additional dimension of the educational
      experience, resident participation in clinic was assessed. Student's t-test was
      used. RESULTS: Total number of cases performed either by senior (before, 1.58 +/-
      0.42 versus after, 1.84 +/- 0.82 cases/day) or junior (before, 0.70 +/- 0.21
      versus after, 0.71 +/- 0.15) residents has not changed (p = NS). Senior
      residents' vascular access and endoscopy rate increased; other categories
      remained stable. Residents' perception of their experience was unchanged. But
      residents' participation in outpatient clinic was significantly decreased
      (before, 66.0% +/- 14.7% versus after, 17.0% +/- 19.9% of clinics covered, p <
      0.005). CONCLUSIONS: The 80-hour limit has had minimal impact on residents'
      operative experience, in case number and variety, and residents' perceptions of
      their educational experience. Residents' reduction in duty hours may have been
      achieved at the expense of outpatient clinic experiences.

PMID- 15848358
TI  - Perceptions and predictors of surgeon satisfaction: a survey of spouses of
      academic surgeons.
AB  - BACKGROUND: Although several studies have addressed the role of spouses in
      physicians' career choices, there is limited data about spousal perception of
      surgeons' careers after training. This study examined satisfaction with surgeons'
      careers and potential contributing factors from a spousal standpoint. STUDY
      DESIGN: A survey of spouses of academic surgeons in 38 participating departments
      was conducted. Questions included demographic information and perceptions of
      career satisfaction and contributing factors. Data were analyzed using
      descriptive statistics, Student's t-test or Mann-Whitney U test, and chi-square
      or Fisher's exact test. RESULTS: Three hundred seventy-nine surveys (27%) were
      returned, with the majority (81%) perceiving their surgeon spouses to be
      satisfied. Contributing factors to surgeon dissatisfaction included: work
      hours/call (42%); practice limitations (18%); reimbursement/income (12%); and
      malpractice/insurance (7%). Dissatisfied surgeons, as perceived by their spouses,
      did not differ from satisfied surgeons in terms of work hours, income
      expectations, geographic desirability, or home involvement. On the other hand,
      predictors of dissatisfied spouses included lack of input into career decisions,
      less satisfaction with location, and lack of their surgeon spouses' participation
      in household and child-care activities. CONCLUSIONS: There are many positive and
      negative aspects to being an academic surgeon. Yet, despite the time commitment,
      work hours per se do not appear to contribute to either surgeon or spousal
      satisfaction. Spousal satisfaction is dependent on surgeon contribution to
      household and childcare activities. Despite the multiple potential detractors
      from an academic surgical career, most surgeons, as perceived by their spouses,
      would not have chosen differently and are satisfied with their career choices.

PMID- 15848357
TI  - Does surgeon frustration and satisfaction with the operation predict outcomes of
      open or laparoscopic inguinal hernia repair?
AB  - BACKGROUND: A surgeon's level of frustration when performing an operation and
      level of satisfaction at completion may be correlated with patients' outcomes. We
      evaluated the relationship between the attending surgeons' frustration and
      satisfaction and recurrence and complications of open and laparoscopic inguinal
      hernia repair. STUDY DESIGN: Men with detectable inguinal hernias were randomized
      to undergo open or laparoscopic herniorrhaphy at 14 Veterans Affairs hospitals.
      After completion of the procedure, surgeons were asked to assess their level of
      frustration during the operation and their overall satisfaction with the
      operative result. Two subjective scales ranging from 1 (not frustrated/not
      satisfied) to 5 (very frustrated/very satisfied) were used to independently
      assess both parameters. Reasons for surgeon frustration were evaluated. Patients
      were followed for 2 years for recurrence and complications. RESULTS: Of 1,983
      patients who underwent hernia repair, 1,622 were available for analysis; 808 had
      open repair and 813 had laparoscopic repair. Surgeons reported less frustration
      and more satisfaction with open than with laparoscopic repair (p = 0.0001 and
      0.0001, respectively). Frustration was associated with a higher rate of hernia
      recurrence at 2 years (adjusted odds ratio, 2.01, 95% CI, 1.15-3.51) in open
      repair, and a higher overall rate of postoperative complications (adjusted odds
      ratio, 1.27, 95% CI, 1.03-1.56) in both open and laparoscopic hernia repair.
      Satisfaction was not correlated with recurrence or complications. CONCLUSIONS:
      The level of a surgeon's frustration during performance of an inguinal
      herniorrhaphy was a better predictor of outcomes of the operation than was
      satisfaction with the procedure. Sources of intraoperative frustration should be
      controlled to improve outcomes.

PMID- 15848359
TI  - Characterization of human nasal septal chondrocytes cultured in alginate.
AB  - BACKGROUND: After serial passages in monolayer, chondrocytes dedifferentiate into
      a fibroblast-like phenotype. Our objective was to determine if culture in
      alginate affects the phenotype of dedifferentiated human nasal septal
      chondrocytes. STUDY DESIGN: Human nasal septal chondrocytes were seeded at low
      density and passaged in monolayer culture. At passages (P) 1, 2, and 3 a portion
      of cells were cultured in alginate. Collagen, glycosaminoglycan (GAG), and DNA
      production were assessed. RESULTS: Chondrocytes in alginate proliferated less yet
      produced higher levels of GAG and collagen than those in monolayer culture.
      Alginate encapsulated P1 chondrocytes stained strongly for GAG and collagen type
      II, and minimally for collagen type I. Monolayer cells at P0 and P1 stained
      positively for collagen type II. All monolayer passages stained positive for
      collagen type I with minimal GAG staining. CONCLUSIONS: Compared with monolayer
      culture, alginate stimulates deposition of GAG and collagen type II, and supports
      the chondrocyte phenotype through P1, but does not promote redifferentiation.

PMID- 15848360
TI  - GATA-3 expression as a predictor of hormone response in breast cancer.
AB  - BACKGROUND: Expression of estrogen receptor-alpha (ERalpha) as determined by
      immunohistochemistry of tumor tissue is currently the most clinically useful test
      to predict hormone responsiveness of breast cancer. Thirty percent of ERalpha
      positive breast cancers do not respond to hormonal therapy. GATA-3 is a
      transcription factor that is expressed in association with ERalpha and there is
      evidence that GATA factors influence response to estrogen. In this pilot study,
      we investigated whether GATA-3 expression is associated with hormone response in
      breast cancer. STUDY DESIGN: Breast cancer tissue was stained for GATA-3
      expression by immunohistochemistry in ERalpha-positive cancers from 28 patients,
      14 of whom were defined as hormone unresponsive (cases) and 14 of whom were age
      matched controls with hormone-responsive, ERalpha-positive cancers (controls).
      RESULTS: Comparing cases and controls, there were no differences in expression of
      ERalpha; progesterone receptor, ErbB2; or tumor grade. Using 20% nuclear staining
      to characterize tumors as GATA-3 positive or GATA-3 negative, 6 of 14 (43%)
      cancers in the hormone-unresponsive group and none of the controls were
      classified as GATA-3 negative (odds ratio, 8.2; 95% confidence interval, 1.2
      infinity; p = 0.031). Using different cut points to characterize GATA-3
      positivity yielded very similar results, indicating a positive association
      between lack of GATA-3 expression and lack of response to hormonal therapy.
      CONCLUSIONS: The study suggests that analyzing ERalpha-positive breast tumors for
      GATA-3 using immunohistochemistry might improve prediction of hormone
      responsiveness. The association between GATA-3 expression and hormone response
      suggests that GATA-3 may play a role in mechanisms controlling response to
      estrogen.

PMID- 15848361
TI  - Fusion of the planes of the liver: an anatomic entity merging the midplane and
      the left intersectional plane.
AB  - BACKGROUND: Alignment of the gallbladder fossa and the round ligament may be
      associated with an almost unknown portal vein branching anomaly. STUDY DESIGN:
      Ultrasonographic imaging allowed detection of this anomaly, which we
      characterized as fusion of the planes of the liver. When appropriate, additional
      specific radiologic examinations were performed (CT scanner supplemented with a
      three-dimensional reconstruction, a biliary cartography, or an angiography).
      Surgical consequences were studied from this series and from the literature.
      RESULTS: Seven patients (0.5%) had the following criteria: 1) round ligament,
      gallbladder fossa, and termination of the portal vein occurring in the same
      plane; 2) typical portal vein branching, including a right posterior branch, left
      branches, and a main medial branch terminated by the Rex's recessus; 3) two main
      hepatic veins without a significant middle hepatic vein; and 4) absence of the
      horizontal part of the left hepatic duct. Fusion of the planes may have been
      involved in two cases of iatrogenic bile duct injury and contraindicated a tumor
      resection and a right-liver donation. A review of the literature revealed that
      lack of recognition of the fusion of the planes led to a high proportion of
      surgical iatrogenic injury. Fusion of the planes could result from incomplete
      development of the central part of the liver, in agreement with embryologic
      knowledge. CONCLUSIONS: Knowledge of the fusion of the planes by hepato-biliary
      surgeons is important. This anomaly may lead to serious complications if it
      remains undetected during liver resection or bile duct surgery.

PMID- 15848362
TI  - Do bone marrow micrometastases correlate with sentinel lymph node metastases in
      breast cancer patients?
AB  - BACKGROUND: Sentinel lymph node biopsies (SLNB) are used to detect axillary
      metastases as an important prognostic indicator for breast cancer patients. Bone
      marrow micrometastases (BMM) have also been shown to predict prognosis. This
      study examines whether SLNB and BMM are associated. STUDY DESIGN: A retrospective
      analysis was performed on 124 stages I to III breast cancer patients treated with
      mastectomy or lumpectomy, SLNB, and bone marrow aspiration between 1997 and 2003.
      SLNB were examined for the presence of metastases by hematoxylin and eosin (H&E)
      stains and also by immunohistochemistry (IHC) for lymph nodes negative by H&E.
      The kappa statistic was used to evaluate the association (agreement) between SLNB
      and BMM. RESULTS: In this study population, 36 patients (29%) had micrometastases
      detected in their bone marrow, and 51 patients (41%) had positive sentinel lymph
      nodes. Of the patients with positive BMM (n = 36), 53% (19 of 36) had positive
      SLNB (14 of 19 by H&E and 5 of 19 by IHC). In patients with negative BMM (n =
      88), 36% (32 of 88) had a positive SLNB (27 of 32 by H&E and 5 of 32 by IHC). The
      kappa statistic and associated 95% confidence interval indicated poor agreement
      between SLNB and BMM (kappa = 0.15; 95% CI = -0.03, 0.32). CONCLUSIONS: There was
      poor agreement between axillary metastases and micrometastases detected in the
      bone marrow. This study suggests that BMM and axillary metastases are not
      concordant findings in most patients.

PMID- 15848365
TI  - Cystadenoma and cystadenocarcinoma of the liver: a single center experience.
AB  - BACKGROUND: Biliary cystadenomas and cystadenocarcinomas comprise 5% of cystic
      lesions in the liver. Cystadenomas are often incorrectly diagnosed as simple
      cysts, which results in inadequate therapy. Recurrence and possible malignant
      transformation are consequences of incomplete excision. Cystadenocarcinomas are
      very rare tumors that are felt to be biologically indolent. STUDY DESIGN: A
      retrospective review of 18 cystadenomas and 4 cystadenocarcinomas treated at the
      Cleveland Clinic from July 1985 to November 2002. RESULTS: All 18 patients with
      cystadenomas were women; mean age was 48 years. The majority (16 of 18) were
      symptomatic. Preoperative CT scans demonstrated cyst(s) with septations in all
      patients. Fifty-five percent had undergone prior intervention(s) to treat the
      cyst. Thirteen patients had complete excision of the cystadenoma, either by
      enucleation or liver resection. None of the patients developed recurrent
      cystadenomas (mean followup 37 months). Of 4 patients with cystadenocarcinoma, 3
      were women; mean age was 60 years. All were symptomatic. Preoperative CT scans
      demonstrated masses with both cystic and solid components. No patient had
      undergone prior intervention. All had a liver resection. Two patients died of
      metastatic disease at 6 and 12 months, respectively. One patient is alive and
      disease-free at 16 years; 1 is alive with metastatic disease 10 years after the
      liver resection. CONCLUSIONS: Cystadenomas are uncommon tumors that are often
      incorrectly diagnosed as simple cysts. Preoperative imaging that demonstrates the
      presence of internal septations highly suggests the diagnosis of cystadenoma.
      Intraoperative biopsy and frozen section(s) are essential, although they are not
      100% accurate. Cystadenomas require complete excision to prevent recurrence and
      the possibility of malignant transformation. Cystadenocarcinomas are very rare.
      Despite complete resection, cystadenocarcinomas can recur in a short period of
      time. The biologic behavior of these tumors can vary widely.

PMID- 15848366
TI  - Safety of carotid endarterectomy in 2,443 elderly patients: lessons from
      nonagenarians--are we pushing the limit?
AB  - BACKGROUND: Elderly patients are a rapidly expanding segment of the population.
      Recent studies suggest that octogenarians have mortality and morbidity after
      carotid endarterectomy (CEA) similar to that in their younger cohort. Outcomes of
      CEA performed in nonagenarians have not been commonly reported; this study seeks
      to determine the safety of CEA in nonagenarians in general practice. STUDY
      DESIGN: All patients in nonfederal Connecticut hospitals undergoing CEA between
      1990 and 2002 were identified using the state discharge database (Chime Inc; ).
      RESULTS: A total of 14,679 procedures were performed during the 12 study years.
      Sixty-four patients were nonagenarians (0.4%). Perioperative mortality was higher
      among nonagenarians (3.1%) compared with younger patients, including the 2,379
      octogenarians (0.6%; p = 0.008, chi-square; odds ratio = 9.1, p = 0.006). No
      statistically significant difference was noted in perioperative stroke rates
      between nonagenarians (3.1%) and octogenarians (1.2%; p = 0.35, chi-square; odds
      ratio 2.3, p = 0.28). Nonagenarians had longer hospital lengths of stay (7.3
      days, p < 0.0001), intensive care unit lengths of stay (1.2 days, p = 0.0013),
      and greater hospital charges ($17,967 +/- $1,907, p < 0.0001) than younger
      patients. Nonagenarians underwent operative procedures more frequently in an
      emergent setting (22%) compared with octogenarians (11%, p < 0.001) and had a
      greater percentage of symptomatic presentations (stroke: 14% versus 11%, p =
      0.04; transient ischemic attack: 8% versus 5%, p = 0.04, respectively). All
      perioperative deaths and strokes occurred in symptomatic nonagenarians (15%
      versus 0%, p = 0.038; 15% versus 0%, p = 0.038; respectively). CONCLUSIONS:
      Carotid endarterectomy is performed in nonagenarians, as a group, with greater
      rates of perioperative mortality and morbidity than in younger patients,
      including octogenarians. But nonagenarians have a greater rate of symptomatic and
      emergent presentations than younger patients, which may account for their
      increased mortality, morbidity, length of stay, and incurred charges.
      Asymptomatic nonagenarians have similar outcomes after carotid endarterectomy
      compared with younger patients, including octogenarians, with low rates of
      mortality and morbidity.

PMID- 15848367
TI  - Use of magnetic resonance imaging in breast oncology.

PMID- 15848368
TI  - What's new in cardiac surgery.

PMID- 15848369
TI  - What's new in general surgery: critical care and trauma.

PMID- 15848370
TI  - Introduction: Symposium on surgery in the elderly patient, part 2.

PMID- 15848371
TI  - Postoperative delirium in the older patient.

PMID- 15848372
TI  - Common orthopaedic problems in the elderly patient.

PMID- 15848373
TI  - Anesthetic pitfalls in the elderly patient.

PMID- 15848374
TI  - Schistosomal portal hypertension.

PMID- 15848375
TI  - Fibromuscular dysplasia of the carotid artery.

PMID- 15848376
TI  - Solitary arteriovenous malformation of the small intestine.

PMID- 15848377
TI  - Percutaneous cephalic vein cannulation (in the Deltopectoral Groove), with
      ultrasound guidance.

PMID- 15848379
TI  - Complete esophageal diversion: a simplified, easily reversible technique.

PMID- 15848380
TI  - Voice changes after thyroidectomy without recurrent laryngeal nerve injury.

PMID- 15848381
TI  - Centennial perspective on burn treatment.

PMID- 15848383
TI  - The role of Claude Bernard and others in the discovery of Horner's Syndrome.

PMID- 15848385
TI  - Characterization of the uterine phenotype during the peri-implantation period for
      LIF-null, MF1 strain mice.
AB  - Leukemia inhibitory factor plays a major role in the uterus and in its absence
      embryos fail to implant. Our knowledge of the targets for LIF and the
      consequences of its absence is still very incomplete. In this study, we have
      examined the ultrastructure of the potential implantation site in LIF-null MF1
      female mice compared to that of wild type animals. We also compared expression of
      proteins associated with implantation in luminal epithelium and stroma. Luminal
      epithelial cells (LE) of null animals failed to develop apical pinopods, had
      increased glycocalyx, and retained a columnar shape during the peri-implantation
      period. Stromal cells of LIF-null animals showed no evidence of decidual giant
      cell formation even by day 6 of pregnancy. A number of proteins normally
      expressed in decidualizing stroma did not increase in abundance in the LIF-null
      animals including desmin, tenascin, Cox-2, bone morphogenetic protein (BMP)-2 and
      -7, and Hoxa-10. In wild type animals, the IL-6 family member Oncostatin M (OSM)
      was found to be transiently expressed in the luminal epithelium on late day 4 and
      then in the stroma at the attachment site on days 5-6 of pregnancy, with a
      similar but not identical pattern to that of Cox-2. In the LIF-null animals, no
      OSM protein was detected in either LE or stroma adjacent to the embryo,
      indicating that expression requires uterine LIF in addition to a blastocyst
      signal. Fucosylated epitopes: the H-type-1 antigen and those recognized by
      lectins from Ulex europaeus-1 and Tetragonolobus purpureus were enhanced on
      apical LE on day 4 of pregnancy. H-type-1 antigen remained higher on day 5, and
      was not reduced even by day 6 in contrast to wild type uterus. These data point
      to a profound disturbance of normal luminal epithelial and stromal
      differentiation during early pregnancy in LIF-nulls. On this background, we also
      obtained less than a Mendelian ratio of null offspring suggesting developmental
      failure.

PMID- 15848386
TI  - Dlx2 over-expression regulates cell adhesion and mesenchymal condensation in
      ectomesenchyme.
AB  - The Dlx family of homeodomain transcription factors have diverse roles in
      development including craniofacial morphogenesis and consists of 6 members with
      overlapping expression patterns. Dlx2 is expressed within the developing
      branchial arches in both the epithelium and mesenchyme and targeted deletion in
      mice has revealed roles in patterning and development of the craniofacial
      skeleton. Defects in Dlx2 null mice include skeletal anomalies of proximal
      branchial arch 1 derivatives while distal elements are largely spared indicating
      redundancy within the Dlx family. We have investigated the function of Dlx2 using
      in ovo electroporation and cell culture. Ectopic expression of Dlx2 within the
      neural tube beginning prior to emigration of neural crest cells at E1.25
      drastically inhibits the migration of transfected cells and induces aggregation
      of transfected neuroepithelial cells within the neural tube at 24 h post
      electroporation. By 48 h post-electroporation, the majority of transfected cells
      formed multicellular aggregates that were found adjacent to the basal side of the
      neural tube and very few Dlx2 expressing cells migrated to the level of the
      branchial arches. Similar results were obtained for Dlx5, suggesting these
      effects may be common to Dlx genes. Electroporation of the Dlx2 expression
      construct into branchial arch mesenchyme induced N-cadherin and NCAM, a dramatic
      increase in cell-cell adhesion relative to controls, and resulted in an increase
      in mesenchymal condensation. These results suggest a role for Dlx genes in
      regulating ectomesenchymal cell adhesion and supports the possibility that the
      skeletal dysmorphology seen in Dlx null mice may derive from abnormalities at the
      condensation stage.

PMID- 15848387
TI  - A molecular link between FGF and Dpp signaling in branch-specific migration of
      the Drosophila trachea.
AB  - The tracheal system of Drosophila embryos achieves its archetypal branching
      pattern through a series of cell migration events requiring the FGF, Dpp, and
      Wg/WNT signaling pathways. To gain insight into tracheal cell migration, we
      performed an F4 EMS mutagenesis screen to generate and characterize new mutations
      resulting in tracheal defects. From 2591 mutagenized third chromosome lines, we
      identified 33 mutations with defects in tracheal development, corresponding to 12
      distinct complementation groups. The new mutations included novel hypomorphic
      alleles of the FGF receptor gene, breathless, and the ETS-domain transcription
      factor gene, pointed. We show that reduced function of either breathless or
      pointed specifically affects migration of the dorsal and ventral tracheal
      branches, more specific functions than previously described for these genes. Our
      analysis reveals that breathless and pointed control dorsal branch migration
      through transcriptional regulation of the Dpp pathway effectors, Knirps and
      Knirps-related, which are necessary for migration of this branch. We further show
      that expression of knirps or knirps-related rescues dorsal but not ventral branch
      migration in the breathless hypomorph. These studies support a model in which
      both the Dpp- and the FGF-signaling pathways control expression of knirps and
      knirps-related, thereby regulating cell migration during dorsal branch formation.

PMID- 15848388
TI  - Genetic dissection of the zebrafish retinal stem-cell compartment.
AB  - In a large-scale forward-genetic screen, we discovered that a limited number of
      genes are required for the regulation of retinal stem cells after embryogenesis
      in zebrafish. In 18 mutants out of almost 2000 F2 families screened, the eye
      undergoes normal embryonic development, but fails to continue growth from the
      ciliary marginal zone (CMZ), the post-embryonic stem-cell niche. Class I-A
      mutants (5 loci) display lower amounts of proliferation in the CMZ, while nearly
      all cells in the retina appear differentiated. Class I-B mutants (2 loci) have a
      reduced CMZ with a concomitant expansion in the retinal pigmented epithelium
      (RPE), suggesting a common post-embryonic stem cell is the source for these
      neighboring cell types. Class II encompasses three distinct types of mutants (11
      loci) with expanded CMZ, in which the progenitor population is arrested in the
      cell cycle. We also show that in at least one combination, the reduced CMZ
      phenotype is genetically epistatic to the expanded CMZ phenotype, suggesting that
      Class I genes are more likely to affect the stem cells and Class II the
      progenitor cells. Finally, a comparative mapping analysis demonstrates that the
      new genes isolated do not correspond to genes previously implicated in stem-cell
      regulation. Our study suggests that embryonic and post-embryonic stem cells
      utilize separable genetic programs in the zebrafish retina.

PMID- 15848389
TI  - Cardiac neural crest is necessary for normal addition of the myocardium to the
      arterial pole from the secondary heart field.
AB  - In cardiac neural-crest-ablated embryos, the secondary heart field fails to add
      myocardial cells to the outflow tract and elongation of the tube is deficient.
      Since that study, we have shown that the secondary heart field provides both
      myocardium and smooth muscle to the arterial pole. The present study was
      undertaken to determine whether addition of both cell types is disrupted after
      neural crest ablation. Marking experiments confirm that the myocardial component
      fails to be added to the outflow tract after neural crest ablation. The cells
      destined to go into the outflow myocardium fail to migrate and are left at the
      junction of the outflow myocardium with the nascent smooth muscle at the base of
      the arterial pole. In contrast, the vascular smooth muscle component is added to
      the arterial pole normally after neural crest ablation. When the myocardium is
      not added to the outflow tract, the point where the outflow joins the pharynx
      does not move caudally as it normally should, the aortic sac is smaller and fails
      to elongate resulting in abnormal connections of the outflow tract with the
      caudal aortic arch arteries.

PMID- 15848390
TI  - Secondary heart field contributes myocardium and smooth muscle to the arterial
      pole of the developing heart.
AB  - The arterial pole of the heart is the region where the ventricular myocardium
      continues as the vascular smooth muscle tunics of the aorta and pulmonary trunk.
      It has been shown that the arterial pole myocardium derives from the secondary
      heart field and the smooth muscle tunic of the aorta and pulmonary trunk derives
      from neural crest. However, this neural crest-derived smooth muscle does not
      extend to the arterial pole myocardium leaving a region at the base of the aorta
      and pulmonary trunk that is invested by vascular smooth muscle of unknown origin.
      Using tissue marking and vascular smooth muscle markers, we show that the
      secondary heart field, in addition to providing myocardium to the cardiac outflow
      tract, also generates prospective smooth muscle that forms the proximal walls of
      the aorta and pulmonary trunk. As a result, there are two seams in the arterial
      pole: first, the myocardial junction with secondary heart field-derived smooth
      muscle; second, the secondary heart field-derived smooth muscle with the neural
      crest-derived smooth muscle. Both of these seams are points where aortic
      dissection frequently occurs in Marfan's and other syndromes.

PMID- 15848391
TI  - Oogenesis in Hydra: nurse cells transfer cytoplasm directly to the growing
      oocyte.
AB  - Oogenesis in Hydra occurs in so-called egg patches containing several thousand
      germ cells. Only one oocyte is formed per egg patch; the remaining germ cells
      differentiate as nurse cells. Whether and how nurse cells contribute cytoplasm to
      the developing oocyte has been unclear. We have used tissue maceration to
      characterize the differentiation of oocytes and nurse cells in developing egg
      patches. We show that nurse cells decrease in size at the same time that
      developing oocytes increase dramatically in volume. Nurse cells are also tightly
      attached to oocytes at this stage and confocal images of egg patches stained with
      the fluorescent membrane dye FM 4-64 clearly show large gaps (10 microm) in the
      cell membranes separating nurse cells from the developing oocyte. We conclude
      that nurse cells directly transfer cytoplasm to the developing oocyte. Following
      this transfer of cytoplasm, nurse cells undergo apoptosis and are phagocytosed by
      the oocyte. These results demonstrate that basic mechanisms of alimentary
      oogenesis typical of Caenorhabditis and Drosophila are already present in the
      early metazoan Hydra.

PMID- 15848392
TI  - The ERRalpha orphan nuclear receptor controls morphogenetic movements during
      zebrafish gastrulation.
AB  - Gastrulation is a process involving cellular commitment and movements whereby the
      three fundamental germ layers are established in vertebrates embryos. Estrogen
      Receptor-Related (ERR) alpha is a nuclear receptor displaying high sequence
      identity to the Estrogen Receptors (ERs). However, ERRalpha is unable to bind and
      to be regulated by estrogens or any natural ligand to date. Whereas recent
      studies have suggested roles for ERRalpha in bone and adipose tissue metabolism
      in the mouse, little is known about its roles during embryonic development. In
      zebrafish embryos, ERRalpha is expressed from the beginning of gastrulation at
      the margin of the blastoderm that represents the presumptive mesendoderm. Using
      loss of function (morpholinos or a dominant-negative version of the protein) and
      gain of function (mRNA injection) strategies, we show here that ERRalpha is
      involved in epiboly and convergent-extension (CE) processes in the zebrafish.
      Altogether, these results propose ERRalpha as a new regulator of morphogenetic
      movement during gastrulation, independently of cell fate determination.

PMID- 15848393
TI  - Retinoic acid-dependent attraction of adult spinal cord axons towards
      regenerating newt limb blastemas in vitro.
AB  - Adult urodele amphibians possess the unique ability to regenerate amputated limbs
      and to re-innervate these regenerating structures; however, the factors involved
      in mediating this re-innervation are largely unknown. Here, we investigated the
      role of retinoic acid (RA) and one of its receptors, RARbeta, in the reciprocal
      neurotropic interactions between regenerating limb blastemas and spinal cord
      explants from the adult newt Notophthalmus viridescens. First, we showed that
      retinoic acid induced directed axonal outgrowth from cultured spinal cord tissue.
      This RA-induced outgrowth was significantly reduced when spinal cord explants
      were pre-treated with either the synthetic RAR pan antagonist, LE540, or the
      specific RARbeta antagonist, LE135. The role of RARbeta was also investigated
      using co-cultured regenerating limb blastemas and spinal cord explants. Blastemas
      induced significantly more axonal outgrowth from the near side of co-cultured
      explants, than from the far side (when cultured less than 1 mm apart). This
      blastema-induced directed outgrowth from co-cultured spinal cord explants was
      also abolished in the presence of the RARbeta antagonist, LE135. These data
      strongly suggest that endogenous retinoic acid is one of the tropic factors
      produced by the blastema and that it may be capable of guiding re-innervating
      axons to their targets. Moreover, this interaction is likely mediated by the
      retinoic acid beta nuclear receptor.

PMID- 15848394
TI  - The slender lobes gene, identified by retarded mushroom body development, is
      required for proper nucleolar organization in Drosophila.
AB  - The nucleolus dynamically alters its shape through the assembly and disassembly
      of a variety of nucleolar components in proliferating cells. While the nucleolus
      is known to function in vital cellular events, little is known about how its
      components are correctly assembled. Through the analysis of a Drosophila mutant
      that exhibits a reduced number of mushroom body (MB) neurons in the brain, we
      reveal that the slender lobes (sle) gene encodes a novel nuclear protein that
      affects nucleolar organization during development. In sle mutant neuroblasts, the
      nucleolus was packed more tightly, forming a dense sphere, and the nucleolar
      proteins fibrillarin and Nop60B were abnormally distributed in the interphase
      nucleolus. Moreover, another nucleolar marker, Aj1 antigen, was localized to the
      center of the nucleolus in a manner complementary to the Nop60B distribution, and
      also formed a large aggregate in the cytoplasm. While developmental defects were
      limited to a few tissues in sle mutants, including MBs and nurse cells, the
      altered organization of the nucleolar components were evident in most developing
      tissues. Therefore, we conclude that Sle is a general factor of nuclear
      architecture in Drosophila that is required for the correct organization of the
      nucleolus during development.

PMID- 15848395
TI  - Expression of epithin in mouse preimplantation development: its functional role
      in compaction.
AB  - The preimplantation development of mammalian embryo after fertilization
      encompasses a series of events including cleavage, compaction, and
      differentiation into blastocyst. These events are likely to be associated with
      substantial changes in embryonic gene expression. In the present study, we
      explored the expression patterns and function of epithin, a mouse type II
      transmembrane serine protease, during preimplantation embryo development. RT-PCR
      analysis showed that epithin mRNAs were detectable during the cleavage stages
      from a 1-cell zygote to the blastocyst. Immunocytochemical studies revealed that
      epithin protein was expressed at blastomere contacts of the compacted 8-cell and
      later embryonic stages. Epithin colocalized with E-cadherin at the membrane
      contacts of the compacted morula-stage embryo as revealed by double-staining
      immunocytochemistry and confocal microscopy, respectively. Post-transcriptional
      epithin gene silencing by RNA interference (RNAi) resulted in the blockade of 8
      cell in vitro-stage embryo compaction and subsequent embryonic deaths after
      several rounds of cell division. These results strongly suggest that epithin
      plays an important role in the compaction processes that elicit the signal for
      the differentiation into trophectoderm and inner cell mass.

PMID- 15848396
TI  - n-Heptyl xanthate adsorption on a ZnS layer synthesized on germanium: an in situ
      attenuated total reflection IR study.
AB  - Adsorption of n-heptyl xanthate on synthesized zinc sulfide was followed in situ
      by monitoring the methylene absorption band at 2925 cm(-1). The zinc sulfide
      surface used in the adsorption experiments was synthesized on a germanium
      internal reflection element using the chemical bath deposition method.
      Characterization of the adsorbent surface was performed by X-ray photoelectron
      spectroscopy. The time needed to reach adsorption equilibrium varied with the
      initial concentration of the aqueous potassium heptyl xanthate solution. The
      amount of adsorbed xanthate ions increased with the concentration of the solution
      within the range studied (10 microM-50 mM). The experimental data are reasonably
      well described by the Langmuir adsorption isotherm. Polarized infrared attenuated
      total reflection (ATR) was used to determine the average orientation of the
      heptyl chains by measuring the absorbance of the infrared beam polarized
      perpendicularly and parallely to the plane of incidence. Measured absorbances
      were corrected for contribution from heptyl xanthate in bulk solution.

PMID- 15848397
TI  - An improved predictive correlation for the induction time of CaCO3 scale
      formation during flow in porous media.
AB  - The induction time, tind, of calcium carbonate precipitation in porous rocks was
      experimentally measured under dynamic conditions at temperatures from 25 to 120
      degrees C with the use of a radiotracer technique, where the gamma-emitting
      nuclide 47Ca was used as a tracer in order to monitor the scale deposition at
      real time. Based upon nucleation theory and experimental observations, the
      following improved correlation is proposed: This equation predicts satisfactorily
      the induction time of calcium carbonate scale formation under specific dynamic
      (flow) conditions in the near-well region (T is the absolute temperature in K,
      and SI is the saturation index, SI=logSR, where SR is the saturation ratio).

PMID- 15848398
TI  - Modeling of adsorption dynamics at air-liquid interfaces using statistical rate
      theory (SRT).
AB  - A large number of natural and technological processes involve mass transfer at
      interfaces. Interfacial properties, e.g., adsorption, play a key role in such
      applications as wetting, foaming, coating, and stabilizing of liquid films. The
      mechanistic understanding of surface adsorption often assumes molecular diffusion
      in the bulk liquid and subsequent adsorption at the interface. Diffusion is well
      described by Fick's law, while adsorption kinetics is less understood and is
      commonly described using Langmuir-type empirical equations. In this study, a
      general theoretical model for adsorption kinetics/dynamics at the air-liquid
      interface is developed; in particular, a new kinetic equation based on the
      statistical rate theory (SRT) is derived. Similar to many reported kinetic
      equations, the new kinetic equation also involves a number of parameters, but all
      these parameters are theoretically obtainable. In the present model, the
      adsorption dynamics is governed by three dimensionless numbers: psi (ratio of
      adsorption thickness to diffusion length), lambda (ratio of square of the
      adsorption thickness to the ratio of adsorption to desorption rate constant), and
      Nk (ratio of the adsorption rate constant to the product of diffusion coefficient
      and bulk concentration). Numerical simulations for surface adsorption using the
      proposed model are carried out and verified. The difference in surface adsorption
      between the general and the diffusion controlled model is estimated and presented
      graphically as contours of deviation. Three different regions of adsorption
      dynamics are identified: diffusion controlled (deviation less than 10%), mixed
      diffusion and transfer controlled (deviation in the range of 10-90%), and
      transfer controlled (deviation more than 90%). These three different modes
      predominantly depend on the value of Nk. The corresponding ranges of Nk for the
      studied values of psi (10(-2)<psi<10(4)) and lambda (10(-12)<lambda<10(8)) are
      10(1)<Nk<10(4) for the diffusion controlled, 10(-3)<Nk<10(1) for the mixed
      diffusion and transfer controlled, and 10(-4)<Nk<10(-3) for the transfer
      controlled, respectively. The study also shows that lower values of psi and
      lambda are favorable for maximum surface adsorption and consequently surface
      tension reduction.

PMID- 15848399
TI  - Adsorption of human insulin and AspB28 insulin on a PTFE-like surface.
AB  - The interactions of human insulin, Zn-free human insulin, and AspB28 insulin with
      a hydrophobic surface were studied by ellipsometry. All three insulin types
      investigated adsorbed with high affinity onto the hydrophobic surface, as the
      plateau of the adsorption isotherm, represented by the irreversible bound
      fraction, was reached at concentrations >10(-3) mg/ml. The plateau values for
      human insulin and Zn-free human insulin could not be distinguished with
      statistical significance, whereas the plateau value for AspB28 insulin was lower
      than those for the two others, with an adsorbed amount corresponding to a
      monolayer of insulin monomers. The results observed may be explained by
      differences in self-association patterns of the insulin types or by enhanced
      charge repulsion between the AspB28 analog and the negatively charged surface.

PMID- 15848400
TI  - Adsorption mechanism of synthetic reactive dye wastewater by chitosan.
AB  - Chitosan was able to remove the color from synthetic reactive dye wastewater
      (SRDW) under acidic and caustic conditions. The effect of the initial pH on SRDW
      indicated that electrostatic interaction occurred between the effective
      functional groups (amino groups) and the dye under acidic conditions. Moreover,
      SRDW adsorption under caustic conditions was also affected by the covalent
      bonding of dye and hydroxyl groups of chitosan. In addition, elution tests
      confirmed that chemical adsorption occurred under acidic conditions, while both
      physical and chemical adsorption appeared under caustic conditions. The spectra
      of attenuated total reflectance Fourier transform infrared spectrometry confirmed
      the functional groups of chitosan that affected the SRDW adsorption. However, the
      maximum adsorption capacities of chitosan increased when the temperature
      increased. The maximum adsorption capacity of chitosan obtained from the Langmuir
      model was 68, 110, and 156 mg g(-1) under a system pH of 11.0 at 20, 40, and 60
      degrees C, respectively. The negative values of enthalpy change (DeltaH), free
      energy change (DeltaG), and entropy change (DeltaS) indicated an exothermic,
      spontaneous process and decreasing disorder of the system, respectively.
      Therefore, the mechanism of SRDW adsorption by chitosan was probably by chemical
      adsorption for a wide range of pH's and at high temperatures.

PMID- 15848401
TI  - Thermodynamics of Pb2+ and Ni2+ adsorption onto natural bentonite from aqueous
      solutions.
AB  - Removal of Pb2+ and Ni2+ from aqueous solutions by sorption onto natural
      bentonite was investigated. Experiments were carried out as a function of
      particle size, the amount of bentonite, pH, concentration of metals, contact
      time, and temperature. The adsorption patterns of metal ions onto followed the
      Langmuir, Freundlich, and Dubinin-Radushkevich isotherms. This included
      adsorption isotherms of single-metal solutions at 303 K by batch experiments. The
      thermodynamic parameters (DeltaH,DeltaS,DeltaG) for Pb2+ and Ni2+ sorption onto
      bentonite were also determined from the temperature dependence. The adsorptions
      were endothermic reactions. The results suggested that natural bentonite is
      suitable as a sorbent material for recovery and adsorption of metal ions from
      aqueous solutions.

PMID- 15848402
TI  - Adsorption and kinetic studies of cationic and anionic dyes on pyrophyllite from
      aqueous solutions.
AB  - The adsorption of cationic Methylene Blue (MB) and anionic Procion Crimson H-EXL
      (PC) dyes from aqueous medium on pyrophyllite was studied. Changes in the
      electrokinetics of pyrophyllite as a function of pH were investigated in the
      absence and presence of multivalent cations. The results show that pyrophyllite
      in water exhibits a negative surface charge within the range pH 2-12.
      Pyrophyllite is found to be a novel adsorbent for versatile removal of cationic
      and anionic dyes. The negative hydrophilic surface sites of pyrophyllite are
      responsible for the adsorption of cationic MB molecules. The adsorption of
      anionic PC dye is possible after a charge reversal by the addition of trivalent
      cation of Al. Nearly 2 min of contact time are found to be sufficient for the
      adsorption of both dyes to reach equilibrium. The experimental data follow a
      Langmuir isotherm with adsorption capacities of 70.42 and 71.43 mg dye per gram
      of pyrophyllite for MB and PC, respectively. For the adsorption of both MB and PC
      dyes, the pseudo-second-order chemical reaction kinetics provides the best
      correlation of the experimental data.

PMID- 15848403
TI  - Electrolyte and pH effects on Pb(II)-calcite sorption processes: the role of the
      PbCO0 (3aq) complex.
AB  - Batch sorption experiments were conducted under conditions of ambient temperature
      and atmospheric PCO2g to determine the effects of electrolyte type, ionic
      strength, and pH on Pb(II) interactions with calcite. For 0.15 M nitrate and
      chloride solutions at pH 8.2, no significant effect of electrolyte type on Pb
      sorption was observed. Varying ionic strength from 0.15 to 0.5 M produced little
      effect on Pb sorption in nitrate compared to chloride solutions in which Pb
      uptake decreased with increasing ionic strength. For a pH range of 7.3-9.4 in
      0.15-0.2 M nitrate solutions, Pb sorption increased from pH 7.3 to 8.5 with a
      subsequent decrease in uptake out to pH 9.4. The trends in electrolyte and pH
      experiments correlate well with those for PbCO0(3aq) speciation, indicating that
      this metal-ligand complex in solution dictates Pb sorption in the system under
      investigation.

PMID- 15848404
TI  - Passivation of the calcite surface with phenylmalonate and benzylmalonate ions.
AB  - We explored the affinity of calcite to adsorbed organic molecules as an approach
      to the conservation of cultural heritage built of marble and limestone. The
      utilization of phenylmalonic and benzylmalonic acids provided a hydrophobic
      adsorptive interface, adequate to prevent processes of aqueous weathering.
      Samples of marble powder (polycrystalline calcite) were impregnated with
      solutions of phenylmalonic and benzylmalonic acid at three concentrations (5 x
      10(-2), 5 x 10(-3), and 5 x 10(-4) M) and different pH values (6.00, 7.00, and
      8.00). The surface charge of the calcite suspensions was determined by
      potentiometric measurements under equilibrium conditions at room temperature in
      aqueous solution of the dicarboxylic acids, in order to understand the influence
      of the electrokinetic potential in the surface association. The adsorbed amounts
      were determined by calculation of the thermodynamic equilibria of solutions. The
      presence of the organic interface on the mineral surface was corroborated by
      Raman spectroscopy and small-angle X-ray scattering (SAXS). The results indicate
      effective adsorption of both dicarboxylic acids as a function of the
      concentration and pH, and several other conditions that favors coulombic
      interaction, an absence of electrophoretic mobility or surface electroneutrality
      related to the solid surface potentials. The coverage of pores by dicarboxylic
      adsorbate modified the geometrical pore shape and the pore size distribution,
      filling all the pores of larger than 80 A diameter, giving as a result a
      mesoporous structure. This change in the surface morphology by organic adsorbates
      constitutes a modification in the diffusional processes of the environment on the
      mineral surface.

PMID- 15848405
TI  - EXAFS study of Zn sorption mechanisms on hydrous ferric oxide over extended
      reaction time.
AB  - The sorption species and coordination environment of zinc sorbed on to hydrous
      ferric oxide (HFO) did not change for aging times up to six months. At an initial
      concentration of 10(4-) M, Zn formed innersphere surface complexes on the surface
      of HFO. Zn was tetrahedrally coordinated with oxygen atoms at ZnO bond distance
      of approximately 1.94-1.97 A with coordination number of approximately 3.8-4.7.
      In the second shell Zn appeared to be coordinated with Fe with a bond distance of
      approximately 3.42-3.49 A. At an initial concentration of 10(3-) M, both
      innersphere and polynuclear complexes were feasible sorption products. The first
      shell was tetrahedrally coordinated with about four oxygen atoms at a bond
      distance of 1.96 A. The second shell could be attributed to either ZnFe or ZnZn
      correlations with almost the same bond distance of 3.42-3.44 A.

PMID- 15848406
TI  - Equilibrium, kinetics, mechanism, and process design for the sorption of
      methylene blue onto rice husk.
AB  - Batch experiments were carried out for the sorption of methylene blue onto rice
      husk particles. The operating variables studied were initial solution pH, initial
      dye concentration, adsorbent concentration, and contact time. Equilibrium data
      were fitted to the Freundlich and Langmuir isotherm equations and the equilibrium
      data were found to be well represented by the Langmuir isotherm equation. The
      monolayer sorption capacity of rice husks for methylene blue sorption was found
      to be 40.5833 mg/g at room temperature (32 degrees C). The sorption was analyzed
      using pseudo-first-order and pseudo-second-order kinetic models and the sorption
      kinetics was found to follow a pseudo-second-order kinetic model. Also the
      applicability of pseudo second order in modeling the kinetic data was also
      discussed. The sorption process was found to be controlled by both surface and
      pore diffusion with surface diffusion at the earlier stages followed by pore
      diffusion at the later stages. The average external mass transfer coefficient and
      intraparticle diffusion coefficient was found to be 0.01133 min(-1) and 0.695358
      mg/g min0.5. Analysis of sorption data using a Boyd plot confirms that external
      mass transfer is the rate limiting step in the sorption process. The effective
      diffusion coefficient, Di was calculated using the Boyd constant and was found to
      be 5.05 x 10(-04) cm2/s for an initial dye concentration of 50 mg/L. A single
      stage batch-adsorber design of the adsorption of methylene blue onto rice husk
      has been studied based on the Langmuir isotherm equation.

PMID- 15848407
TI  - Kinetic modeling of the adsorption of basic dyes by kudzu.
AB  - The use of kudzu, a rapidly growing, high-climbing perennial leguminous vine, for
      the adsorption of basic dyes from aqueous solution has been investigated at
      various initial dye concentrations, masses of kudzu, and agitation rates. The
      extent and rate of adsorption of the three basic dyes (Basic Red 22, Basic Yellow
      21, and Basic Blue 3) were analyzed using a pseudo-first-order and a pseudo
      second-order kinetic model. While both rate mechanisms provided an acceptable
      degree of correlation with the experimental sorption rate data, the pseudo-second
      order model gave a much higher degree of correlation, suggesting that this model
      could be used in design and simulation applications.

PMID- 15848408
TI  - The impact of ionic strength on the adsorption of protons, Pb, Cd, and Sr onto
      the surfaces of Gram negative bacteria: testing non-electrostatic, diffuse, and
      triple-layer models.
AB  - Bacterial surface adsorption reactions are influenced by electric field effects
      caused by changes in ionic strength; however, existing datasets are too sparse to
      definitively constrain these differences or to determine the best way to account
      for them using thermodynamic models. In this study, we examine the ionic strength
      dependence of proton and metal adsorption onto the surfaces of Pseudomonas
      mendocina and Pseudomonas putida by conducting proton, Cd(II), Pb(II), and Sr(II)
      adsorption experiments over the ionic strength range of 0.001 to 0.6 M. Chosen
      experimental results are thermodynamically modeled using a non-electrostatic
      approach, a diffuse layer model (DLM), and a triple-layer model (TLM). The
      results demonstrate that bacterial surface electric field effects are negligible
      for proton, Cd, and Pb adsorption onto P. putida and P. mendocina, and that the
      discrete site non-electrostatic model developed in this study is adequate for
      describing these reactions. The extent of Sr adsorption is influenced by changes
      in the bacterial surface electric field; however, the non-electrostatic model
      better describes Sr adsorption behavior than the DLM or TLM. The DLM and TLM
      greatly overpredict the effect of the electric field for all adsorption reactions
      at all ionic strengths tested.

PMID- 15848409
TI  - The influences of solid-phase organic constituents on the partition of aliphatic
      and aromatic organic contaminants.
AB  - The influence of natural organic matter (NOM) constituents on contaminant
      distribution coefficients was evaluated by determining the Koc values of aromatic
      and aliphatic organic compounds (solutes) with clays modified with both aromatic-
      and aliphatic-rich organic constituents. The studied compounds consisted of
      naphthalene, phenanthrene, n-pentane, and 2,3,4-trimethylmethane; the solid
      samples comprised two clays with little organic content, kaolinite and Ca
      montmorillonite. Two aliphatic surfactants and three aromatic dyes, sorbed to the
      clays, served as reference NOM constituents. For solutes of comparable water
      solubilities, the organic-carbon normalized distribution coefficients (Koc) of
      the aliphatic solutes between sorbed aliphatic organic matter and aqueous
      solution slightly exceed those of the aromatic solutes. By contrast, the aromatic
      solutes exhibited higher Koc values than did the aliphatic compounds with sorbed
      aromatic-rich organic matter. The difference in Koc values could be attributed to
      either comparable solubility parameters or the difference in the chemical
      structure between nonionic organic solutes and specific components of the
      simulated NOM. The much higher Koc values observed for the aromatic solutes
      indicate that the NOM composition is a major factor determining the NOC
      environmental distribution.

PMID- 15848410
TI  - Selective crystallization of calcium salts by poly(acrylate)-grafted chitosan.
AB  - The biopolymer chitosan was chemically modified by grafting polyacrylamide or
      polyacrylic acid in a homogeneous aqueous phase using potassium persulfate (KPS)
      as redox initiator system in the presence of N,N-methylene-bis-acrylamide as a
      crosslinking agent. The influence of the grafted chitosan on calcium salts
      crystallization in vitro was studied using the sitting-drop method. By using
      polyacrylamide grafted chitosan as substrate, rosette-like CaSO4 crystals were
      observed. This was originated by the presence of sulfate coming from the
      initiator KPS. By comparing crystallization on pure chitosan and on grafted
      chitosan, a dramatic influence of the grafted polymer on the crystalline habit of
      both salts was observed. Substrates prepared by combining sulfate with chitosan
      or sulfate with polyacrylamide did not produce similar CaSO4 morphologies.
      Moreover, small spheres or donut-shaped CaCO3 crystals on polyacrylic acid
      grafted chitosan were generated. The particular morphology of CaCO3 crystals
      depends also on other synthetic parameters such as the molecular weight of the
      chitosan sample and the KPS concentration.

PMID- 15848411
TI  - Rheological behavior in water of complexes formed from poly(sodium 2-(acrylamido)
      2-methylpropanesulfonate) and positively charged rodlike micelles.
AB  - The viscoelastic behavior of aqueous solutions of an ionic complex formed from
      poly(sodium 2-(acrylamido)-2-methylpropanesulfonate) and rodlike mixed micelles
      of dimethyloleylamine oxide (DMOAO) and hexadecyltrimethylammonium chloride
      (CTAC) was investigated under oscillatory conditions. The DMOAO/CTAC mixed
      micelles exhibited high zero-shear viscosities (eta0) depending on the mole
      fraction of CTAC in the mixed micelle (Y) in the range 0Y0.25. The addition of
      the polyanion had no effect on the rheological behavior of the mixed micelles
      when Y<0.02 at an ionic strength (mu) of 0.2. However, when Y was increased to a
      certain level (Yc), eta0 decreased drastically; Yc depended on mu but not on the
      polymer concentration. These observations indicate the formation of an ionic
      complex between the polymer and micelle when YYc. The reciprocal of steady-state
      compliance (Je(-1)) began to decrease gradually at Y approximately Yc and then
      leveled off at Y>0.06. The relaxation time (tau) was found to be more strongly
      dependent on Y. Thus, the large decrease in eta0 was attributed mainly to a
      decrease in tau while the number density of junctions decreased only slightly.
      Therefore, it is concluded that polymer-micelle complex maintains a rodlike
      structure with some entanglements remaining at Y<0.12.

PMID- 15848412
TI  - Polymer-surfactant and protein-surfactant interactions.
AB  - The phase behavior and some physicochemical properties of homopolymers (HP) and
      hydrophobically modified (HMP) polymers, as well as of polyelectrolytes (PE) and
      proteins (PR), in the presence of aqueous surfactants, or their mixtures, are
      discussed. Mixing the above components gives rise to the formation of organized
      phases, whose properties are controlled by polymer and/or surfactant content,
      temperature, pH, and ionic strength. Depending on the nature, concentration, and
      net charge of both solutes, molecular solutions, polymer-surfactant complexes,
      adsorption onto micelles and vesicles, gels, liquid crystalline phases, and
      precipitates are observed. Such rich polymorphic behavior is the result of a
      complex balance between electrostatic, excluded volume, van der Waals, and other
      contributions to overall system stability. It is also modulated by the molecular
      details and architecture of both the polymer and the surfactant. Different
      experimental methods allow investigation of the above systems and getting
      information on the nature of polymer-surfactant interactions (PSI). Surface
      adsorption and thermodynamic methods, together with investigation of the phase
      diagrams, give information on the forces controlling PSI and on the existence of
      different phases. Conductivity, QELS and viscosity allow estimating the size and
      shape of polymer-surfactant (protein-surfactant) complexes. Optical microscopy,
      cryo-TEM, AFM, NMR, fluorescence, and relaxation methods give more information on
      the above systems. Use of the above mixtures in controlling gelation, surface
      covering, preparing dielectric layers, and drug release is suggested.

PMID- 15848413
TI  - Interfacial stabilization of organic-aqueous two-phase microflows for a
      miniaturized DNA extraction module.
AB  - Organic-aqueous liquid (phenol) extraction is one of many standard techniques to
      efficiently purify DNA directly from cells. The cell components naturally
      distribute themselves into the two fluid phases in order to minimize interaction
      energies of the biological components with the surrounding solvents. The membrane
      components and protein partition to the interface between the organic and aqueous
      phases while the DNA stays in the aqueous phase. The aqueous phase is then
      removed with a purified DNA sample. This work studies the first steps towards
      miniaturizing this liquid extraction technique in a microfluidic device. The
      first step is to understand how the two liquid phases behave in microchannels.
      Due to the interfacial tension between the two liquid phases, novel approaches
      must be examined in order to obtain interfacial stability under flow conditions.
      The stability of the organic-aqueous interface is improved by reducing the
      interfacial tension between the two phases by incorporating a surfactant into the
      aqueous phase. The variation of the interfacial tension as a function of
      surfactant concentration is also quantified in this work. This has led to the
      ability to create stable stratified microflows in both a dual inlet and three
      inlet microfluidic systems. Also, the first step in understanding biological
      interactions at the organic-aqueous interface is investigated using a
      fluorescently labeled bovine serum albumin protein.

PMID- 15848415
TI  - Sedimentation in bidisperse and polydisperse colloids.
AB  - We introduce a simple force and flux balance model for sedimentation and creaming
      in high volume fraction, polydisperse colloidal suspensions. The model is set
      alongside monodisperse and bidisperse sedimentation data for latex spheres, and
      we suggest that the broadening of the larger species sedimentation profile
      observed in the bidisperse case is linked to the particle pressure gradient
      arising from the smaller species. The model gives a satisfactory qualitative
      description of real emulsion creaming data, but implies either that the effective
      droplet radius is larger than the measured droplet radius, or that the effective
      background viscosity is reduced. Increasing the particle pressure gradient
      results in interface broadening at short times. We propose that the smallest
      emulsion droplets contribute to this broadening.

PMID- 15848414
TI  - The interaction between DNA and cationic lipid films at the air-water interface.
AB  - The interaction between DNA and positively charged dioctadecyldimethylammonium
      bromide (DODAB) and DODAB/disteroylphosphatidylcholine (DSPC) monolayers at the
      air-aqueous interface was studied by a combination of the surface film balance
      and Brewster angle microscopy. In presence of DNA, the Pi-A isotherm of the
      cationic monolayer shifts to larger mean molecular areas due to the electrostatic
      interaction with DNA while the typical liquid expanded-liquid condensed phase
      transition for DODAB monolayers disappear and the monolayer remains to be in the
      liquid expanded phase. Furthermore, the morphology of the film dramatically
      changes, where the large dendritic-like condensed aggregates observed for DODAB
      monolayers vanish. The charge density of the monolayer was varied by using mixed
      monolayers with the zwitterionic DSPC and no large effect was observed on the
      interaction with DNA. By modeling the electrostatic interactions with the
      linearized Poisson-Boltzmann equation using the finite-element method and taking
      into account the assumption in the dielectric constants of the system, it was
      possible to corroborate the expansion of the cationic monolayer upon interaction
      with DNA as well as the fact that DNA does not seem to penetrate into the
      monolayer.

PMID- 15848416
TI  - Magnetite nanoparticles with tunable gold or silver shell.
AB  - Fe3O4 nanoparticles with size approximately 13 nm have been prepared successfully
      in aqueous micellar medium at approximately 80 degrees C. To make Fe3O4
      nanoparticles resistant to surface poisoning a new route is developed for coating
      Fe3O4 nanoparticles with noble metals such as gold or silver as shell. The shell
      thickness of the core-shell particles becomes tunable through the adjustment of
      the ratio of the constituents. Thus, the route yields well-defined core-shell
      structures of size from 18 to 30 nm with varying proportion of Fe3O4 to the noble
      metal precursor salts. These magnetic nanoparticles were characterized by X-ray
      diffraction (XRD), transmission electron microscopy (TEM), FTIR, differential
      scanning calorimetry (DSC), Raman and temperature-dependent magnetic studies.

PMID- 15848417
TI  - Multi-Monte Carlo method for coagulation and condensation/evaporation in
      dispersed systems.
AB  - A new multi-Monte Carlo (MMC) method is promoted to consider general dynamic
      equation (GDE) for particle coagulation and condensation/evaporation. MMC method
      introduces the concept of a "weighted fictitious particle" and is based on time
      driven Monte Carlo technique, constant number of fictitious particles technique,
      and constant volume technique. MMC method for independent coagulation, for
      independent condensation/evaporation, and for simultaneous coagulation and
      condensation/evaporation are validated by some special cases in which analytical
      solutions exist, in which numerical results agree with corresponding analytical
      solutions well. Furthermore, the computation cost of MMC method is low enough to
      be applied in engineering computation and general scientific quantitative
      analysis.

PMID- 15848418
TI  - Dispersion of TiN in aqueous media.
AB  - The dispersion of TiN powders in aqueous media was studied through XPS, zeta
      potential, adsorption, sedimentation, and rheology measurements. XPS showed that
      there are TiO2, TiN, and TiOxNy sites on the TiN particle surface. In the absence
      of dispersant, the isoelectric point (pH(IEP)) of the TiN particles was at pH
      2.2. Based on the surface properties of TiN particles, a cationic polymer,
      polyethylene imine (PEI), was selected as a dispersant. In the presence of PEI,
      the pH(IEP) shifted from pH 2.2 to pH 11.10. It was evidenced that TiN slurries
      could be stabilized around pH 9.50 with 1-2 wt% PEI as dispersant. Subsequently,
      TiN slurries with solid content as high as 57 vol% were developed and exhibited
      dilatant rheological behavior at high shear rate. The results showed that PEI is
      an effective dispersant for TiN in aqueous media.

PMID- 15848419
TI  - An explanation of dispersion states of single-walled carbon nanotubes in solvents
      and aqueous surfactant solutions using solubility parameters.
AB  - Dispersions of single-walled carbon nanotubes in various solvents and aqueous
      surfactant emulsions were investigated to correlate the degree of dispersion
      state with Hansen solubility parameters (deltat2=deltad2+deltap2+deltah2). It was
      found that the nanotubes were dispersed or suspended very well in the solvents
      with certain dispersive component (deltad) values. They were precipitated in the
      solvents with high polar component (deltap) values or hydrogen-bonding component
      (deltah) values. The solvents in the dispersed group occupied a certain region in
      a 3-dimensional space of three components. The surfactants with a lipophilic
      group equal to and longer than decyl, containing 9 methylene groups and 1 methyl
      group, contributed to the dispersion of nanotubes in water. The surfactants in
      the dispersed group had a lower limit in the dispersive component (deltad) of the
      Hansen parameter.

PMID- 15848420
TI  - Aging mechanisms of perfluorocarbon emulsions using image analysis.
AB  - The aging mechanisms of perfluorocarbon emulsions were investigated using image
      analysis. Oil-in-water emulsions of two perfluorocarbons, n-perfluorohexane and
      perfluorodecalin, were prepared with three emulsifiers, Lecithin, Span 20, and
      Pluronic F-68. The effect of the temperature and the replacement of water by an
      aqueous phase consisting of a microbial culture medium were also studied. The
      emulsions were prepared by sonication and their stability was followed through
      analysis of the evolution of mean droplet size. The results indicate that the
      stability of perfluorocarbon in water emulsions depends on all the parameters
      investigated and that two aging mechanisms, coalescence and molecular diffusion,
      may take place. Analysis of the evolution of the mean droplet size during long
      time periods indicate that coalescence is more common than previously reported
      for these systems and seems to be favored by a temperature increase.

PMID- 15848421
TI  - Preparation and characterization of polymer composite multilayers on SiO2.
AB  - Poly(diallyldimethylammonium chloride) (PDADMAC) and poly(sodium 4
      styrenesulfonate) (PSS) have been consecutively adsorbed onto 1.5-microm charged
      silica (SiO2) particles. Time-dependent adsorption studies indicate that, due to
      the strong ionic charge of the dissociated polycation in water, adsorption is
      complete in less than 30 min. Indications of the maximum adsorption density,
      changes in surface charge, and stability of the layered particles are
      demonstrated through adsorption isotherms and electrophoretic mobility (EPM)
      measurements. Further stability of the PDADMAC layer is demonstrated through
      multiwashing with ultra pure deionized water. Preliminary desorption studies of
      the PSS layer also illustrate a stabilized two-layer system. Due to the nature of
      the electrostatic charges on the surface of the SiO2 core particles and both
      polyelectrolytes in aqueous media, the use of polyelectrolytes as layering
      elements serves as a model for the assembly of time-released drug delivery
      particle systems.

PMID- 15848422
TI  - Characterization of organic phases in the interlayer of montmorillonite using
      FTIR and 13C NMR.
AB  - The molecular conformation and mobility of the intercalated surfactant molecules
      cetyltrimethylammonium bromide (CTMAB) have been studied using Fourier transform
      infrared spectroscopy (FTIR) and high-resolution single-pulse 13C magic angle
      spinning nuclear magnetic resonance (13C SP MAS NMR) spectroscopy. The
      conformation and mobility of alkyl chains were found to be a function of the
      surfactant concentration. The splitting of the methylene scissoring mode at 1473
      1463 cm(-1) and the rocking mode at 730-720 cm(-1) in FTIR are considered to be
      diagnostic of the packing density increase of the intercalated surfactants within
      the clay gallery. Compared with the 13C SP MAS NMR spectrum of CTMAB in the bulk
      state, 1-3 ppm upfield chemical shifts for end-methyl (deltaC16) and methylene
      (deltaC15, deltaC2-14) of the intercalated surfactant molecules in the hybrids
      indicate a freer conformational situation. For these hybrids, the conformational
      freedom decreases with increased of surfactant concentration. In addition, on
      approximately 2 ppm downfield shift for the C1 carbon atom in the hybrids with
      higher surfactant content suggests a special local environment. This study
      demonstrates the different mobility of carbon atoms in the intercalated alkyl
      chain.

PMID- 15848423
TI  - Distribution of amines in water/AOT/n-hexane reverse micelles: influence of the
      amine chemical structure.
AB  - The distribution of different aliphatic and aromatic amines: n-butylamine (n-BA),
      isobutylamine (i-BA), tert-butylamine (t-BA), piperidine (PIP), N,N
      dimethylaniline (DMA) and N-methylaniline (MA) in water/sodium 1,4-bis(2
      ethylhexyl)sulfosuccinate(AOT)/n-hexane reverse micelles was investigated by
      steady-state fluorescence measurements. The partition constants were measured by
      an indirect method based on the effect that amine partitioning exert on the
      bimolecular rate of the reaction between a microphase incorporated fluorophore
      (Ru(bpy)2+(3)) and the quencher, (Fe(CN)3-(6)). For MA, that can act as a
      quencher of the fluorophore a direct method was used. The results show that
      primary amines have larger partition constants than the secondary ones. For
      tertiary amines the distribution constants were practically negligible. Laser
      flash photolysis experiments confirmed that tertiary amines, both aliphatic and
      aromatic, are not incorporated to the micellar pseudophase. The effect of the
      amine structure on the partition constant was analyzed through linear solvation
      free energy relationships (LSER) using solute parameters and compared with those
      obtained for alcohols. Hydrogen bond interactions with the AOT polar heads appear
      to be the main driving force for the distribution of amines between the organic
      and micellar pseudophases, whereas the size of the alkyl or aromatic group tends
      to hinder it.

PMID- 15848424
TI  - A surface adsorption/reaction mechanism for gold oxidation by copper(II) in
      ammoniacal thiosulfate solutions.
AB  - Literature data for gold dissolution in ammoniacal copper(II) thiosulfate
      solutions is reinterpreted on the basis of adsorption and mixed potential theory.
      The dissolution reaction appears to take place via the adsorption of copper(II)
      ammonia-thiosulfate onto the gold surface, forming the adsorbed species
      perpendicular to Au(S2O3)nCu(NH3)-(2n-2)p. Equilibrium constants for the
      formation of these species from Cu(NH3)(2+)m are in the range Kads=172-510 (molar
      units) for m=4, n=1 or 2, and p=2 or 3. These complexes decompose with a rate
      constant of kAu=1.7 x 10(-4)molm(-2)s(-1), to produce Au(S2O3)(3-)2 and
      Cu(NH3)+(3) or Cu(NH3)+(2), where the copper(I) complexes in solution are re
      equilibrated to the more stable species Cu(S2O3)3-(2) and Cu(S2O2)5-(3).

PMID- 15848425
TI  - Calorimetric study of the reactions of n-alkylphosphonic acids with metal oxide
      surfaces.
AB  - The reaction enthalpies for the solution-phase self-assembly of n-alkylphosphonic
      acids on the surfaces of TiO2 and ZrO2 have been determined using isothermal
      titration calorimetry at 298 K. The reaction enthalpies were negative
      (exothermic) for methyl- and n-octylphosphonic acids and positive (endothermic)
      for n-octadecylphosphonic acid with both metal oxides. The enthalpy/energy
      analysis showed that the net enthalpy of the formation of self-assembled
      monolayers (SAMs) at solid-liquid interface can be presented as follows: DeltaHr=
      D-(DeltaHsol+DeltaHdil)-(ES-ESAM), where D is the binding energy of the SAM
      molecules with the solid; DeltaHsol and DeltaHdil are the enthalpies of
      dissolution and dilution; ES and ESAM are the surface energies of bare solid and
      SAM, respectively. This equation predicted an increase (and the sign change) of
      the reaction enthalpy as the alkyl group in n-alkylphosphonic acid increased,
      which explained the experimental data. Using this equation, the binding energy
      (D) in the SAMs of n-octyl- and n-octadecylphosphonic acids were estimated: 55+/
      5 kJ/mol (for ZrO2) and 58+/-7 kJ/mol (for TiO2).

PMID- 15848426
TI  - Preparation and characterization of LiMn2-yCoyO4 spinels by low heating solid
      state coordination method.
AB  - Cathode material LiMn2-yCoyO4 spinels were prepared by annealing the mixed
      precursors, which were synthesized by a low heating solid state coordination
      method using lithium acetate, manganese acetate, cobalt acetate, and oxalic acid
      as original materials. The structures and morphologies of the LiMn2-yCoyO4
      spinels were investigated as a function of annealing temperature and time. The
      results showed that all samples in different annealing temperature and time had
      the same spinel structure. There were some growth and agglomeration in the
      particles when annealing temperature increased from 450 to 650 degrees C. And the
      crystal structure was more perfect at the upper temperature. In addition, the
      electrochemical properties of LiMn2-yCoyO4 spinels used as cathode material for
      lithium-ion batteries were studied in detail in this paper.

PMID- 15848427
TI  - Beta zeolite colloidal nanocrystals supported on mesoporous MCM-41.
AB  - Zeolite-based composite materials prepared by the embedding of the beta zeolite
      nanophase from aqueous colloidal solution into matrices of preformed Si(Al)MCM-41
      mesoporous molecular sieves have been characterized by different methods (XRD,
      SEM, FTIR, N2 adsorption, and TPD of NH3). Their potential as catalysts for
      toluene disproportionation has been compared to mechanical mixtures of freeze
      dried nanobeta crystallites with Si(Al)MCM-41 mesoporous materials. It is found
      that the zeolite catalyst efficiency is not substantially changed by the presence
      of mesopores belonging to the matrix. It is suggested that formation of
      intergrown aggregates from the colloidal nanobeta particles provides own highly
      developed textural mesoporosity that makes the contribution of the diffusional
      alleviation of the support negligible.

PMID- 15848428
TI  - High dispersion and electrocatalytic properties of palladium nanoparticles on
      single-walled carbon nanotubes.
AB  - Palladium (Pd) nanoparticles were electrochemically dispersed on single-walled
      carbon nanotubes (SWNTs) by electroreduction of octahedral Pd(IV) complex formed
      on the SWNT surface. The structure and nature of the resulting Pd-SWNT composites
      were characterized by transmission electron microscopy and X-ray diffraction. The
      electrocatalytic properties of the Pd/SWNT electrode for hydrazine oxidation have
      been investigated by cyclic voltammetry; high electrocatalytic activity of the
      Pd/SWNT electrode can be observed. This may be attributed to the high dispersion
      of palladium catalysts and the particular properties of SWNT supports. The
      results imply that the Pd-SWNT composite has good potential applications in fuel
      cells.

PMID- 15848429
TI  - Spectroscopic and optical characterization of porphyrin chromophores incorporated
      into ultrathin polyimide films.
AB  - Polyamic acid (PAA) containing free-base porphyrin and zinc(II) porphyrin
      chromophores was synthesized by copolymerization of diphenylether-type
      tetracarboxylic dianhydride and diamines. The monolayer of the alkylamine salts
      of PAA (PAASs) at the air/water interface was deposited on solid substrates by
      the Langmuir-Blodgett (LB) technique. The PAAS LB films thus obtained were
      converted to polyimide (PI) LB films by chemical treatment. The fluorescence of
      porphyrin moieties in the PI LB film was observed, because of the weak electron
      accepting properties of the diphenylether unit. Therefore, the photophysically
      important processes, such as photoinduced electron transfer, excitation energy
      transfer, and excitation energy migration could be investigated in relation to
      the layered nanostructures of the ultrathin PI films. The fluorescence spectrum
      suggested that the aggregation of porphyrin moieties in the PI LB films was
      effectively prevented by the use of polymeric films. The surface plasmon (SP)
      measurement showed that the thickness of the monolayers was 0.9-1.0 nm for PAAS
      films and 0.32-0.40 nm on average for PI LB films. The absorption dichroism of
      the Soret band of porphyrin indicated that porphyrin moieties in the PAAS and PI
      LB films are oriented in parallel with the substrate. These results showed that
      the orientation and the spatial distribution of porphyrin units can be
      efficiently regulated in the PI LB films in a nanometer dimension.

PMID- 15848430
TI  - Membrane potential across anion-exchange membranes in acidic solution system.
AB  - The membrane potential across anion-exchange membranes in H2SO4 and Na2SO4
      solutions was measured, and the experimental results were fitted to the theory in
      the 2-1 electrolyte system based on the Donnan equilibrium and the Nernst-Planck
      flux equations. For the Na2SO4 solution, the Donnan potential makes a significant
      contribution to the membrane potential, but for the H2SO4 solution, the diffusion
      potential significantly contributes to the membrane potential. The diffusion
      potential has a greater contribution to the membrane potential across AEM-2 with
      a high water content than that across AEM-1. These results suggest that a proton
      with a high mobility can move without substantial influence of electrostatic
      interaction in a positively charged membrane.

PMID- 15848431
TI  - Quantifying the effect of membrane potential in chemical osmosis across bentonite
      membranes by virtual short-circuiting.
AB  - Clay liners are charged membranes and show semipermeable behavior regarding the
      flow of fluids, electrical charge, chemicals and heat. At zero gradients of
      temperature and hydrostatic pressure, a salt concentration gradient across a
      compacted clay sample induces not only an osmotic flux of water and diffusion of
      salt across the membrane but also an electrical potential gradient, defined as
      membrane potential. Laboratory experiments were performed on commercially
      available bentonite samples in a rigid-wall permeameter connected to two
      electrically insulated fluid reservoirs filled with NaCl solutions of different
      concentrations and equipped with Ag/AgCl electrodes to measure the electrical
      potential gradient. The effect of membrane potential could be cancelled out by
      short-circuiting the clay with the so-called virtual shortcut. The potential
      gradient across the sample is brought to zero with a negative feedback circuit.
      It was observed that the water flux and the diffusion of Cl- were hindered by the
      occurrence of a membrane potential, indicating that an electroosmotic counterflow
      is induced. Flow parameters were calculated with modified coupled flow equations
      of irreversible thermodynamics. They were in excellent agreement with values
      reported in the literature. Comparing the method of short-circuiting with a study
      elsewhere, where the electrodes were physically short-circuited, it was shown
      that the virtual shortcut is more appropriate because physically short-circuiting
      induces additional effects that are attributed to the fluxes.

PMID- 15848432
TI  - Adsorption of silanes bearing nitrogenated Lewis bases on SiO2/Si (100) model
      surfaces.
AB  - The present paper describes the one-pot procedure for the formation of self
      assembled thin films of two silanes on the model oxidized silicon wafer, SiO2/Si.
      SiO2/Si is a model system for other surfaces, such as glass, quartz, aerosol, and
      silica gel. MALDI-TOF MS with and without a matrix, XPS, and AFM have confirmed
      the formation of self-assembled thin films of both 3
      imidazolylpropyltrimethoxysilane (3-IPTS) and 4-(N-propyltriethoxysilane
      imino)pyridine (4-PTSIP) on the SiO2/Si surface after 30 min. Longer adsorption
      times lead to the deposition of nonreacted 3-IPTS precursors and the formation of
      agglomerates on the 3-IPTS monolayer. The formation of 4-PTSIP self-assembled
      layers on SiO2/Si is also demonstrated. The present results for the flat SiO2/Si
      surface can lead to a better understanding of the formation of a stationary phase
      for affinity chromatography as well as transition-metal-supported catalysts on
      silica and their relationship with surface roughness and ordering. The 3-IPTS and
      4-PTSIP modified SiO2/Si wafers can also be envisaged as possible built-on
      silicon thin-layer chromatography (TLC) extraction devices for metal
      determination or N-heterocycle analytes, such as histidine and histamine, with
      "on-spot" MALDI-TOF MS detection.

PMID- 15848433
TI  - A refractive tilting-plate technique for measurement of dynamic contact angles.
AB  - The contact angle is a critical parameter in liquid interface dynamics ranging
      from liquid spreading on a solid surface on earth to liquid motion in partially
      filled containers in space. A refractive tilting-plate technique employing a
      scanning laser beam is developed to conduct an experimental study of a moving
      contact line, with the intention of making accurate measurements of the contact
      angle. The technique shows promise as an accurate and potentially fully automated
      means to determine the velocity dependence of the contact angle at the
      intersection of the interface between two transparent fluids with a transparent
      solid surface. Ray tracing calculations are included to reinforce the measurement
      concept. The principal experiments were conducted at speeds ranging from 0.05 to
      1.00 mm/s, both advancing and receding, using an immiscible liquid pair
      (nonane/formamide) in contact with glass. The contact angle was found to depend
      for practical purposes only on the sign of the velocity and not on its magnitude
      for the range of velocities studied. Other observations revealed a bimodal
      behavior of the contact line that depends on which liquid first contacts the
      glass, with resulting drift in the dynamic contact angle with time.

PMID- 15848434
TI  - Nonlinear evolution of thin liquid films dewetting near soft elastomeric layers.
AB  - The nonlinear evolution of thin liquid films dewetting near soft elastomeric
      layers is examined in this work. Evolution equations are derived by applying the
      lubrication approximation and assuming that van der Waals forces in the liquid
      cause the dewetting and that the solid can be described as a linear viscoelastic
      material. Two cases are examined: (i) a liquid layer resting on an elastomer
      bounded from below by a rigid substrate, and (ii) an elastomer overlying a thin
      liquid film bounded from below by a rigid substrate. Linear stability analysis is
      carried out to obtain asymptotic relations which are then compared against
      solutions of the full characteristic equations. In the liquid-on-solid case,
      numerical solutions of the evolution equations show that van der Waals forces
      cause thinning of the liquid film and thickening of the elastomeric solid beneath
      film depressions. Inclusion of a short-range repulsive force suggests that
      regular patterns may form in which ridges of fluid rest on depressions in the
      solid. In the solid-on-liquid case, the van der Waals forces cause the solid
      layer to break up before the liquid film can dewet. The results presented here
      support the idea that the dewetting of thin liquid films might be exploited to
      create topographically patterned surfaces on soft polymeric solids.

PMID- 15848435
TI  - The influence of flotation agent concentration on the wettability and flotability
      of polystyrene.
AB  - The fundamental flotation process is the formation of a flocculant by air bubbles
      and solid particles in an aqueous solution. The behavior of plastic particles is
      significantly influenced by the wettability of the plastics. In this article the
      reciprocal relationship between the flotability and wettability of polystyrene
      was studied at different concentrations of flotation agents, particularly
      terpineol, polyethylene glycol dodecyl ether, tannic acid, and calcium
      lignosulfonate. The conclusions obtained demonstrate the dissimilar action of
      flotation depressants, what means different adhesion mechanisms on a plastic
      surface.

PMID- 15848436
TI  - Surface thermodynamic properties of polyelectrolyte multilayers.
AB  - Multilayer architectures of polyelectrolytes fabricated by the layer-by-layer
      technique (LbL) on pretreated polymeric and inorganic substrates were studied by
      contact angle measurements. Poly(diallyldimethylammonium chloride), PDADMAC, and
      poly(sodium 4-styrenesulfonate), PSS, were used as polyelectrolytes. Contact
      angle data were used to calculate the van der Waals and Lewis acid-base
      components of the surface tension of the investigated surfaces. Knowledge of
      these quantities provides valuable information on surface composition, coating
      density, and possible interactions of the surface with other substances. Unusual
      wetting behavior of PDADMAC layers upon prewetting of the multilayer surfaces was
      found and described in terms of surface tension changes. A model of polymer chain
      rearrangement upon wetting was proposed to explain this behavior.

PMID- 15848437
TI  - Surface thermodynamic functions of dilute solutions of methylcyclohexanols in
      ethylene glycol.
AB  - Surface thermodynamic functions (surface entropy, surface enthalpy, and surface
      composition) of dilute solutions of 2-, 3-, and 4-methylcyclohexanol in ethylene
      glycol were obtained using surface tension measurements at various temperatures.
      Surface excess values and surface mole fractions were obtained from Gibbs
      equation and extended Langmuir model respectively. The results show that all
      methylcyclohexanols are surface active in ethylene glycol. The lyophobicity of
      solutes decreases with increasing temperature. The presence of a maximum point in
      the surface entropy diagram in all systems is explained by the formation of
      clathrate-like solvates at the surface of these systems.

PMID- 15848438
TI  - Solubilization by different-sized surfactant mixtures.
AB  - The solubilization phenomenon was investigated in mixed surfactant systems. The
      solubilization power of a mixed surfactant reaches its maximum at a particular
      temperature at each mixing ratio of surfactants. When the mole fraction of C4E1
      in the total surfactant (w1 value) was varied in a water/C12E5/C4E1/decane
      system, the minimum mole fraction of total surfactant in the system necessary to
      obtain a single microemulsion phase (xi value) was almost unchanged for w1<0.3,
      whereas it increased remarkably for w1>0.8. The molar solubilization capacity
      (Cs=(1-xi)/xi) of the mixed surfactant decreased remarkably for w1<0.3, whereas
      it decreased gradually for w1>0.8. The result [Formula: see text] is due largely
      to the characteristic of the function xi(Cs)=1/(1+Cs), specifically, [Formula:
      see text] , where dxi/dw1=(dxi/dCs)(dCs/dw1). The partial molar solubilization
      capacity (Cs) of C4E1 was negative at almost all w1, but the Cs value of C12E5
      went through a maximum on the addition of C4E1. Propanol (a cosurfactant) has the
      same effect on the solubilization phenomenon in the water/C12E6/propanol/heptane
      system. In the water/C12E5/C12E7/decane system, the Cs value of each surfactant
      did not vary greatly as the mixing ratio of surfactants was varied. The Cs and xi
      values were close to molar additivity for each mixing ratio.

PMID- 15848439
TI  - PFGSE-NMR study of the self-diffusion of sucrose fatty acid monoesters in water.
AB  - The micellization of pure monosubstituted sucrose fatty acid esters in water,
      namely sucrose octanoate, sucrose decanoate, sucrose laurate, sucrose dodec-5-cis
      enoate, sucrose myristate, and sucrose palmitate, has been investigated by means
      of two NMR methods, pulsed field gradient spin-echo NMR (PFGSE-NMR), giving
      access to the self-diffusion coefficients of free molecules and micelles in
      solution, and the ERETIC method (electronic reference to access in vivo
      concentrations) for the measurement of concentrations by external calibration of
      a synthetic NMR signal. The early micellar regions and, when possible, the
      premicellar regions were investigated. By this method, we obtained the
      hydrodynamic radii of micelles, displaying a linear progression in relation to
      the chain length and an accurate determination of critical micellar concentration
      (CMC) for each sucrose ester. The effect of the regiochemistry of fatty chain
      grafting has been investigated, showing special behavior for 1'-O-sucrose
      palmitate.

PMID- 15848440
TI  - Mixed micelle behavior of Pluronic L64 and Triton X-100 with conventional and
      dimeric cationic surfactants.
AB  - The mixed micellar properties of a triblock copolymer, Pluronic L64,
      (EO)13(PO)30(EO)13, and a nonionic surfactant, Triton X-100, in aqueous solution
      with conventional alkyl ammonium bromides and their dimeric homologues were
      investigated with the help of fluorescence and cloud point measurements. The
      composition of mixed micelles and the interaction parameter, beta, evaluated from
      the critical micelle concentration (cmc) data for different mixtures using
      Rubingh's and Motomura's theories are discussed. It has been observed that the
      mixed micelle formation between monomeric/dimeric alkyl ammonium bromides and L64
      was due to synergistic interactions which increase with the increase in
      hydrophobicity of the cationic component. On the other hand, synergistic mixing
      was observed in the mixed micelles of Triton X-100 and monomeric cationic
      surfactants, the magnitude of which decreases slightly with the increase in
      hydrophobicity of the cationic component. Antagonistic interactions were observed
      in the case of Triton X-100 and dimeric cationic surfactants.

PMID- 15848441
TI  - Drop deformation dynamics and gel kinetics in a co-flowing water-in-oil system.
AB  - Drop deformation and superimposed gel kinetics were studied in a fast continuous
      flow process for a water-in-oil system. Highly monodisperse drops were generated
      in a double capillary and then deformed passing through a narrowing rectangular
      channel geometry. Nongelling deformation experiments were used to establish the
      process and compare it with existing theories. Thereafter, temperature induced
      drop gelation was included to study its effect on deformation and gel kinetics on
      short timescales and at high temperature gradients. The disperse phase was a
      kappa-carrageenan solution with additional sodium and potassium ions for gelation
      experiments. Sunflower oil was used for the continuous phases. Nongelling
      experiments showed that shear forces are able to deform drops into ellipsoids. A
      comparison with the small deformation theory by Taylor was surprisingly good even
      when drop deformation and flow conditions were not in steady state. Superimposed
      gelation on the deformation process showed clearly the impact of the altered
      rheological properties of the dispersed and continuous phase. Deformation first
      increased on cooling the continuous phase until the onset of gel formation, where
      a pronounced decrease in deformation due to increasing droplet
      viscosity/viscoelasticity was observed. Drop deformation analyses were then used
      to detect differences in gelation kinetics at high cooling rate within process
      times as short as 1.8 s.

PMID- 15848442
TI  - A study of the interaction of dodecyl sulfobetaine with cationic and anionic
      surfactant in mixed micelles and monolayers at the air/water interface.
AB  - The miscibility and interactions between components in mixed adsorbed films and
      micelles containing zwitterionic (dodecyl sulfobetaine--DSB) and cationic
      (dodecyltrimethylammonium bromide) or anionic (sodium dodecyl sulfonate)
      surfactant, respectively, have been investigated. The molecular interactions have
      been quantified by the values of the excess free energy of adsorption
      (DeltaGS,Exc) and micelle formation (DeltaGM,Exc). The obtained results indicate
      nonideal behavior of the investigated mixtures since the values of DeltaGS,Exc
      and DeltaGM,Exc) are negative. Moreover, it has been found that DSB interact more
      strongly with anionic surfactant as compared to cationic surfactant owing to
      different structure of mixed monolayers and micelles.

PMID- 15848443
TI  - Sedimentation of a cylindrical particle in a Carreau fluid.
AB  - The drag coefficient of an isolated, rigid cylindrical particle in a Carreau
      fluid is evaluated. The result of numerical simulation reveals that, in general,
      the shear-thinning nature of a Carreau fluid yields a drag coefficient smaller
      than that for the corresponding Newtonian fluid. Also, the smaller the Reynolds
      number, the more appreciable the decrease of the drag coefficient as the
      relaxation time constant of the Carreau fluid increases. The influence of the
      index parameter of a Carreau fluid on the drag coefficient depends largely on the
      magnitude of the relaxation time constant and is insensitive to the Reynolds
      number. Only if the relaxation time constant is sufficiently large is the
      influence of the index parameter on the drag coefficient significant. If the
      Reynolds number and/or the relaxation time constant is sufficiently large, the
      flow field upstream of a particle becomes asymmetric to that downstream. In
      general, the influence of the index parameter, the relaxation time constant, and
      the Reynolds number on the flow field follows the order index
      parameter<relaxation time constant<Reynolds number.

PMID- 15848444
TI  - Analysis of the response of suspended colloidal soft particles to a constant
      electric field.
AB  - A network model, originally designed for an electrokinetic study of soft particle
      suspensions, has been used for an in-depth analysis of the physical behavior of
      these systems under the action of an externally applied DC electric field. The
      versatility of the network simulation method used makes it possible to obtain
      information readily not only about the electrophoretic mobility, but also about
      any physical variable of interest at all points around the suspended particle:
      electric potential, ion concentrations, fluid velocity. The field-induced
      polarization of the double layer is described in terms of the dependence of these
      and other derived variables (volume charge density, electric field components,
      ion flux components) on the distance to the membrane-solution interface. In
      contrast to colloidal suspensions of hard particles, which basically depend on
      just two parameters (the reciprocal Debye length multiplied by the particle
      radius, kappaa, and the zeta potential, zeta), soft particle suspensions require
      a wider parameter set. First, there are two characteristic diffusion lengths in
      the system (one inside the membrane and the other in the solution) and two
      geometrical lengths (the core radius a and the membrane thickness (b-a)).
      Furthermore, there is the fixed charge density inside the membrane (and possibly
      a surface charge density over the core) that cannot be represented by a zeta
      potential. Finally, the parameter that characterizes the interaction between the
      fluid and the permeable membrane, gamma, strongly influences the behavior of the
      system. Dependences on all these parameters (except the geometrical ones) are
      included in this study.

PMID- 15848445
TI  - A theory on bubble-size dependence of the critical electrolyte concentration for
      inhibition of coalescence.
AB  - The interaction of pairs of bubbles with equal diameters grown on adjacent
      capillaries in aqueous magnesium sulfate solutions is studied by varying
      electrolyte concentration and bubble diameter by Tsang, Koh and Koch [Y.H. Tsang,
      Y.-H. Koh, D.L. Koch, J. Colloid Interface Sci. 275 (2004) 290] (referred to as
      TKK hereafter). They find that the critical concentration to prevent coalescence,
      Ct, increases as the equivalent diameter, deq, decreases. In fact, Ct is found to
      scale as deq(-1.2). This dependence is stronger than that predicted by Prince and
      Blanch (Ct approximately deq(-0.5)) (referred to as PB [M.J. Prince, H.W. Blanch,
      AIChE J. 36 (1990) 1425] hereafter) on the basis of a postulation that
      lubrication pressure due to Marangoni stresses inhibit coalescence. TKK postulate
      instead that bubbles are stabilized by hydration structures. We further
      illustrate here that when hydration force term is added to the equation of motion
      of the film thinning process, predicted values of critical concentration are
      found to scale as deq(-1). The current prediction shows a much better agreement
      with the experimental results than that proposed by PB. This suggests previous
      assumption that immobility of the interface by Marangoni effect as the dominant
      mechanism of inhibition of coalescence in an electrolytic solution is inaccurate
      [M.J. Prince, H.W. Blanch, AIChE J. 36 (1990) 1425, G. Marrucci, Chem. Eng. Sci.
      24 (1969) 975].

PMID- 15848446
TI  - Organic/inorganic hybrid nano-microstructured coatings on insulated substrates by
      electrospray deposition.
AB  - Organic/inorganic hybrid nano-microstructured coatings on insulated polymer films
      were prepared by electrospray deposition (ESD) from an acrylic resin/silica sol
      blend solution. The surface morphologies of the coated films were observed using
      scanning electron microscopy (SEM). The SEM images showed that a nano-microscaled
      fibrous structure was formed on the film. The fiber diameter decreased from 4.4
      microm to 600 nm with the increase in the silica sol content. Energy-dispersive X
      ray analysis also revealed that silica atoms were homogeneously distributed in
      the fibrous structure on the polymer film. These results indicated that the ESD
      method is potentially a useful option for producing nano-microstructured coatings
      on not only conductive, but also insulating surfaces.

PMID- 15848447
TI  - Effect of ozone treatment on ammonia removal of activated carbons.
AB  - In this work, activated carbons (ACs) were modified by ozone treatment to enhance
      the efficiency of removal of ammonia gas over the ACs. Surface properties of the
      ACs were confirmed by X-ray photoelectron spectroscopy (XPS) analysis and N2
      adsorption isotherms at 77 K were investigated by BET and D-A methods to
      characterize the specific surface area, total pore volume, and micropore volume.
      The ammonia removal efficiency was confirmed by the gas-detecting tube technique.
      The results showed that the specific surface area and micropore volume of ACs
      were slightly destroyed as the ozone treatment time increased. However, the ozone
      treatment led to an increase in ammonia removal efficiency of ACs, mainly due to
      an increase of acid functional groups, such as carbonyl and ether groups, on
      carbon surfaces. It was revealed that the improvement of ammonia removal
      efficiency of ACs was greatly affected by the interfacial acid-base interactions
      between modified ACs and basic ammonia adsorbate.

PMID- 15848448
TI  - A new method for bidimensional analysis of interferometric patterns of liquid
      films.
AB  - A new method for bidimensional analysis of interferometric patterns of wetting
      liquid films obtained with the captive bubble technique is described. This method
      replaces one-dimensional analysis along various intensity profiles with analysis
      of one average intensity profile. The advantage is to concentrate the surface
      characteristics of the whole film image into a single intensity profile.

PMID- 15848449
TI  - Influence of socioeconomic and ethical factors on people's behaviour regarding
      the use of cadaveric organs.
AB  - An organ donation is based on feelings of human solidarity and altruism. This
      approach, however, has not improved the organ shortage problem. The following
      suggestions might help to dismantle the persistent barrier linked to organ
      donation. (1) Society should be aware that during our lifetime we might be as
      much potential organ recipients as organ donors. (2) Educational campaigns should
      integrate the notion that cadaver organs are an irreplaceable source of health
      for every member of society. (3) Communication campaigns should illustrate that
      in allowing the use of our organs after death, we are, in fact, sharing a chance
      to prolong health for everybody, including perhaps ourselves. Furthermore, people
      need to acknowledge that using body parts is acceptable, and part of a tacit
      agreement between all members of society. Making a live organ donation to which
      the donor is emotionally related is a pressure-free decision. On the contrary,
      the donation of cadaver organs is influenced by negative factors. Conversely,
      self-interest and resistance to offering the body of a loved one to a stranger
      may make donation much more difficult if the current message is not modified. In
      an international survey of 242 transplantation professionals, with a 57% response
      rate, 70% to 83% agreed with this proposal. An international public survey has
      recently been finished, showing some results about the public's knowledge about
      religious opinions concerning transplantation, suggesting that religious
      institutions should assume a leadership role to give information about their
      positions. On the other hand, partial results concerning public attitudes
      regarding economic support to organ donation indicate that final data may be of
      interest. The creation of a Task Force with representatives from the World Health
      Organization, UNESCO, churches, and leaders of the global transplantation
      community may be key to joint efforts as a means to modify negative attitudes, to
      develop a new philosophy, and to deliver a new message to society.

PMID- 15848450
TI  - Organ donation: key factors influencing families' decision-making.
AB  - AIM: To clarify the decision-making and bereavement needs of family members who
      had organ donation discussed with them; to provide a rationale for further
      preparation of professionals involved in this sensitive work. METHODS: This work
      used a 3-year longitudinal design. A sample of 49 family members who had donation
      discussed with them, were recruited. At 3 to 5, 13 to 15, and 18 to 26 months
      postbereavement, face-to-face interviews and two, self-completed; psychometric
      measures, the Beck Depression Inventory II and the Grief Experience Inventory,
      were used with participants who chose to donate. Single interviews were carried
      out with participants who declined donation. Data were analyzed using a
      comparative, thematic approach and multivariate statistics, focusing on detection
      of important similarities and differences between cases. FINDINGS: Four main
      categories were identified that illustrated the issues that influenced families'
      ability to agree or decline donation and their perception of the decision-making
      process. The categories were concerns about knowledge of the deceased's donation
      wish, views held by the extended family about donation, giving meaning to the
      death and events that occurred in the hospital that were perceived as positive or
      negative. The role of children in the decision-making about organ donation was
      highlighted. In conclusion, hospital care affected participants' donation
      decision-making and appeared to impact on subsequent grief. To facilitate
      decision-making and bereavement that is uncomplicated by questions about brain
      injury and subsequent death, families needed time to understand the information
      given, care in the way and context that information was shared and attention to
      their emotional needs.

PMID- 15848451
TI  - Changing attitude to organ donation and transplantation in university students
      during the years of medical school in Italy.
AB  - The shortage of organ donations is a major limiting factor in transplant
      programs. Since a favorable attitude of health professionals to organ donation
      can positively influence the decision of families of potential donors, educating
      physicians early in their careers may become crucial in this setting. The aim of
      this study was to compare medical student opinions on organ donation and
      transplantation at different stages in their undergraduate career. METHODS:
      Medical students were prospectively surveyed in their first and fourth years by
      an anonymous 10-item questionnaire. RESULTS: The 100 of 195 (51.3%) students
      completed both questionnaires including 29 men, of an overall cohort mean age
      23.7 (range, 22-32 years). 91% of the students had attended classical or
      scientific high school and 83% were Catholic. Their attitude to transplantation
      remained strongly positive (96% vs 92%, fourth vs first year). 96% of the fourth
      year students would accept an human donor organ or an artificial organ (vs 95% of
      first year) and 91% would accept an animal organ (vs 84%). The students showed a
      positive attitude to organ donation (96% vs 91%, fourth vs first year). Most of
      them were prepared to donate their organs after death (88% vs 87%). 63% of the
      fourth year students signed a donor card. In conclusion, medical student
      attitudes to organ donation and transplantation are highly positive, but do not
      improve during the first 3 years of Medical School. An educational program is
      therefore needed.

PMID- 15848452
TI  - Impact of a "direct approach" to live kidney donation in the British Indo-Asian
      community.
AB  - Although a general imbalance exists between the demand for renal transplants and
      the supply of suitable organs, the shortfall is particularly severe for patients
      from the Indo-Asian (I-A) community. It seems unlikely that this will be remedied
      by any increase in cadaveric donation. Our aim was to increase the rate of live
      donor transplantation (LDT) in the I-A population through a direct approach to
      patients and their families, in a culturally acceptable environment by an Asian
      transplant coordinator. Whereas an increase in LDT was seen in the I-A population
      over the period of review, 1997 to 2003, 15 compared with none prior to 1997,
      significant attrition was seen within the program, with only 10% of the original
      cohort coming to donation. There are multiple reasons for this including medical,
      social and psychological.

PMID- 15848453
TI  - Transplantation activity in the Organizzazione Centro-Sud Trapianti: a
      retrospective study from 1999 to March 2004.
AB  - BACKGROUND: The Organizzazione Centro-Sud Trapianti (OCST) was set up in 1998 to
      coordinate the organ procurement and transplantation activity of 9 italian
      regions (Abruzzo, Basilicata, Calabria, Campania, Lazio, Molise, Sardinia,
      Sicily, and Umbria), each referring to a local Regional Transplant Center. The
      aim of the present study was to estimate organ donation and transplantation rates
      in the OCST from 1999 to March 2004. MATERIALS AND METHODS: A retrospective study
      of organ donors and transplantation activity in the OCST during the study period
      was performed, pointing out donor epidemiological data, such as age and sex
      ratio, causes of death, reasons for discarding, and transplantation rates. Donors
      reported to the OCST were divided into 6 groups: A (October 1998-December 1999),
      B (2000), C (2001), D (2002), E (2003), and F (January-March 2004). RESULTS: From
      1999 to March 2004, 2272 potential donors were reported to the OCST. The
      nonharvested donors rate increased up to 52% (Group F), which was lower than the
      previous period (Group E, 64%), but higher than in 1999 (Group A, 43%). The major
      contributing factor was family opposition, which was 38% in 2002 and 41% in 2003.
      CONCLUSIONS: The introduction of the OCST into the field of organ transplantation
      has yielded an increase in organ donation and transplantation activity within the
      regions that set it up from 1999-2003. This trend is a consequence of the growth
      of reported donors from the intensive care unit, which grew 12.7% from 2002 to
      2003. From the data analysis of the first months of 2004, we expect confirmation
      of this trend.

PMID- 15848454
TI  - Prospective audit of deaths at a teaching hospital.
AB  - We undertook a prospective audit of all the deaths in the trauma unit, the
      emergency unit, and the intensive care units to estimate the number of potential
      organ donors in the hospital and identify the reasons for nonreferral of
      potential donors. The transplant coordinators undertook daily visits to the above
      units and documented all of the deaths occurring in the previous 24 hours. The
      patient records were reviewed, and the medical and nursing staff interviewed to
      determine the precise circumstances surrounding the death. Seven of the 14 deaths
      in the neurosurgical intensive care unit were related to the head injury, and
      five were certified brain dead and referred as an organ donor. Fifty-eight of 83
      deaths in the trauma unit were head injury related; however, only eight were
      eventually certified brain dead and referred. In the emergency unit, only one of
      76 patients who died was certified brain dead and referred as an organ donor.
      Although many of the deaths in the above units are related to a head injury or
      cerebral event, very few are actually certified brain dead. All potential donors
      who were certified brain dead were referred to the transplant team.

PMID- 15848455
TI  - The Dutch donor registry: registration rate of hospital personnel, living kidney
      donors, and patients.
AB  - INTRODUCTION: In the Netherlands 13.3 million citizens were contacted by the
      Dutch donor registry to indicate whether they consented or objected to become an
      organ/tissue donor after death. Nearly 4.7 million individuals are now
      registered, which is a 35.1% response rate. We wondered whether kidney patients,
      living kidney donors, and health personnel would have comparable response rates.
      METHODS AND RESULTS: A total of 239 individuals were interviewed, of whom 52%
      indicated to be registered. The highest registration rate was found for hospital
      personnel (66%) followed by living kidney donors (51%) and patients (38%). In
      general, more women than men (57% vs 47%) had returned their registration form.
      CONCLUSION: In the Dutch general public the willingness to make their decision
      known during life to donate organs/tissue after death is rather low. Presumably
      motivated individuals (eg, hospital personnel and living kidney donors) scored
      significantly better, but even in these subgroups 34% and 49%, respectively, were
      nonresponders.

PMID- 15848456
TI  - Living paid organ transplantation results in unacceptably high recipient
      morbidity and mortality.
AB  - The ethical debate surrounding the payment of living unrelated donors continues
      despite very little evidence regarding the outcome. The aim of this audit was to
      identify the scale of the problem and assess the results of patients undergoing
      these procedures. The large Indo-Asian population within our region has a high
      demand for renal replacement therapy and transplantation. These patients have a
      limited chance of receiving a transplant for several reasons and some resort to
      traveling abroad, against medical advice, to procure an unrelated donor kidney
      transplant. Following an initial audit in our region, a national audit was
      conducted within the UK. A total of 23 patients were identified, all of whom had
      done so against medical advice. Mortality from causes directly related to
      transplantation was high in this group (35%), as was graft loss. The overall rate
      of successful transplants was only 44% (overall graft loss was 56%) in the short
      term. The information regarding both donor and recipient, provided from the
      transplanting center, was inadequate in all cases. These results, which almost
      certainly represent an underestimate of an ongoing situation, reinforce the
      standpoint that organ trading is associated with unacceptable risks and poor
      outcomes. The basis of this trade in organs is based on monetary rather than
      clinical criteria and such exploitation of both donor and recipient lead us to
      conclude that this practice cannot be endorsed and even the most desperate
      dialysis patients should be reminded of the unacceptable risks involved in this
      practice.

PMID- 15848457
TI  - Living-unrelated (paid) renal transplantation--ten years later.
AB  - Due to the increase of organ shortage and still inadequate development of cadaver
      transplantation, many end-stage patients from the Balkan region travel mostly to
      India to buy a kidney. Despite all the ethical dilemmas and discussions, organ
      sales is present nowdays in Third-World countries. Sixteen patients (13 from
      Macedonia and 3 from Kosovo, SCG) were observed clinically during a period of 10
      years. Recipients of mean age 36.5 years (range 10 to 58) displayed the following
      underlying diseases: chronic glomerulonephritis (n = 5), urethral valves with
      reflux (n = 2), ADPKD (n = 1), hypertensive nephropathy (n = 4), lithiasis (n =
      1), and unknown cause of ESRD (n = 3). The donor population was young (22 to 29
      years). Most patient records did not include data on HLA, cross-match, MLC, kind
      of surgery, or usual pretransplant workup. The immunosuppressive protocol
      included CyA, PRED, and AZA or MMF. All transplanted patients were followed on an
      outpatient basis in our department; patients with complications were
      hospitalized. The 1, 3, 5, and 10 year Kaplan Meier graft survival rates were
      78.6%, 50.2%, 33.3%, and 18.8%, respectively. Seven patients were lost (43.7%),
      two during the first month after transplantation, two at the end of the first
      year, and three at 5, 6, and 8 years thereafter. The main reasons for death were
      severe pulmonary infections with sepsis, hepatitis B with liver cirrhosis, Kala
      Azar, CMV, and cancer of the colon. Five grafts were lost due to repeated
      rejection episodes and chronic graft nephropathy. The last three cases remained
      with good renal function and actual serum creatinine values of 135 +/- 9. In view
      of this experience, the authors cannot recommend this type of transplantation,
      not only from the ethical point of view, but also from frequent medical and
      surgical complications which are sometimes life threatening.

PMID- 15848458
TI  - Afghan refugees in Iran model renal transplantation program: ethical
      considerations.
AB  - During 23 years of civil war in Afghanistan, there has been a continuous flow of
      more than 5 million refugees out of the country. Iran has hosted about 40% of all
      refugees. The majority have resided outside of camps with opportunities to
      integrate locally, having access to the Iranian labor market and government
      services, such as dialysis and transplantation. Iran also has adopted a
      compensated living unrelated donor renal transplantation program in which
      foreigners can receive transplants from living related donors or volunteer living
      unrelated donors of the same nationality. In June 2004, among 241 refugees with
      end-stage kidney disease in Iran, 179 were on hemodialysis and 62 underwent renal
      transplantation. Nine patients received kidneys from living related donors, 1
      from a spouse, 50 from Afghani living unrelated donors, and 1 from a cadaveric
      donor. No refugee had been used as a kidney donor to an Iranian patient.
      Transplantation of all Afghan refugees in need and the absence of their use as
      kidney donors to Iranian patients proffer strong evidence against commercialism
      and a reason to believe that the Iran Model transplantation is practiced with
      ethical standards. In the last 2 years since the civil war has ended, returning
      these patients to Afghanistan has raised important ethical concerns. Repatriation
      of dialysis patients and transplant recipients may be tantamount to their deaths.
      It is expected that The Transplantation Society and the World Health Organization
      will establish links with the United Nations High Commissioner for Refugee
      Offices to provide humanitarian assistance to these patients.

PMID- 15848459
TI  - The UK National Potential Donor Audit.
AB  - As part of a series of measures designed to improve organ donation rates in the
      United Kingdom, a potential donor audit has been established by UK Transplant.
      The audit will identify the number of patients who could be solid organ donors
      and will establish the obstacles to donation. Results from the first full year of
      the audit indicate that the overall relative refusal rate for heart-beating solid
      organ donation is 41.5%. The age and gender of the potential heart-beating donor
      has little impact on the relative refusal rate, but relatives of ethnic minority
      groups are more than twice as likely to deny consent than those of white
      potential heart-beating donors.

PMID- 15848460
TI  - Changes in notification and demographics of deceased donors during the past
      decade in the state of Michigan, USA.
AB  - From 1993 to 2003 there have been significant changes in the number and
      demographics of deceased donors referred to the organ procurement organization
      (OPO) in the state of Michigan (USA). It was the aim of this study to document
      the magnitude of these changes and attempt to explain them. There has been a 26
      fold increase in the number of reported in-hospital deaths from 1993 to 2003.
      Most of these calls (96%) concerned patients who were already dead and thus not
      suitable for organ donation. There has also been a 72% increase in the number of
      antemortem calls, but there has been only a 30% increase in the number of organ
      donors, primarily because the majority of the deceased individuals referred for
      donation (57% in 2003) do not meet the criteria for brain death. The median age
      of donors over the past 10 years has increased from 31 to 45. The proportion of
      African-American donors increased from 9.8% in 1993 to 21.3% in 2003. An increase
      in the age of donors and the increased frequency of cerebrovascular accidents as
      the cause of death of donors may be a reflection of changes in criteria for
      donation. Mandatory reporting of hospital deaths has resulted in an increase in
      notification to the OPO but has not had a major impact on the number of organ
      donors. On the other hand, increased donation from African-Americans indicates
      that public information programs may be contributing to the increased donation
      from this segment of the population.

PMID- 15848461
TI  - Ethical and legal issues in non-heart-beating organ donation.
AB  - Procurement of kidneys and livers from non-heart-beating donors (NHBDs) raises
      ethical and legal issues that need to be considered carefully before wider use of
      these donors. Although NHBDs were used in kidney transplantation as early as the
      1960s, retrieval of these organs is by no means universally accepted today. From
      a medical point of view, these organs have long been considered "marginal"
      because the majority show delayed or impaired graft function. Legal problems
      include determination of death by cardiopulmonary criteria, the issue of proper
      consent, and the use of organ preservation measures. Among ethical issues raised
      are the observance of the Dead-donor Rule, the decision-making surrounding
      resuscitation, the withdrawal of life-support, the respect for a dying patient
      and the dead body, as well as proper information to and guidance for the family.
      In the Netherlands NHB donation was pioneered in the Maastricht Medical Center in
      1980s. Today, all seven transplant centers retrieve and transplant organs from
      these donors, and NHBDs have become an important source of transplantable kidneys
      and livers. Recent legislation in the Netherlands also supports the use of NHBDs
      by making possible the use of organ preservation measures after circulatory
      arrest, even in the absence of family consent. As a result, one of every three
      kidneys transplanted in the Netherlands in 2004 was obtained from a NHBD. In this
      study, Dutch NHBD protocols, practice, and results are analyzed and compared with
      international practices.

PMID- 15848462
TI  - Kidney transplantation from donors aged 65 years or more as single or dual
      grafts.
AB  - AIM: The organ shortage and aging donor population force transplant centers to
      accept donors previously considered unusable for kidney transplantation. We
      report the experience of two Italian transplant centers with single (SKTx) and
      dual (DKTx) kidney transplantation from donors aged 65 years or more. METHODS:
      The study population comprised 75 SKTx (mean donor age 70.5 years) and 28 DKTx
      (mean donor age 75.0 years). Kidneys from donors with a calculated admission
      creatinine clearance <50 mL/min, a Karpinski's score on kidney biopsy between 5
      and 7, or both were allocated to DKTx. Grafts with better function or lower
      biopsy scores were employed for SKTx. RESULTS: Delayed graft function occurred in
      45.3% of SKTx and in 39.3% of DKTx. After a mean follow-up period of 30.0 +/-
      19.5 months, the acute rejection rate was 24.0% in SKTx and 7.1% in DKTx. Mean
      serum creatinine was 1.8 +/- 0.9 and 1.8 +/- 1.3 mg/dL in SKTx, and 1.8 +/- 1.6
      mg/dL and 1.3 +/- 0.2 mg/dL in DKTx at 1 and 5 years, respectively. Patient
      survival was 93.3% and 91.2% in SKTx, and 92.9% and 92.9% in DKTx at 1 and 5
      years, respectively. Graft survival was 92.0% and 88.3% in SKTx, and 89.3% and
      89.3% in DKTx at the same time intervals. Keeping preservation time below 16
      hours and avoiding calcineurin inhibitors were both associated with improved
      graft survival and function. CONCLUSION: Careful donor selection, short
      preservation time, and tailored immunosuppression allow safe and efficient use of
      elderly donor kidneys.

PMID- 15848463
TI  - Donor kidneys with small renal cell cancers: can they be transplanted?
AB  - INTRODUCTION: The purpose of this study was to determine whether incidentally
      discovered, small renal cell cancers (RCC) in donor kidneys can be excised and
      safely transplanted. METHODS: The Israel Penn International Transplant Tumor
      Registry database was searched and all small RCC that were identified and
      resected prior to transplantation of deceased and living donor kidneys were
      reviewed. Patient demographics, tumor characteristics, recurrence, and survival
      were examined. RESULTS: Fourteen kidneys were identified in which small RCC were
      noted at the time of procurement and where the tumors were excised ex vivo and
      then transplanted. Eleven kidneys were obtained from living related donors and
      three were from deceased donors. Median tumor size was 2 cm (range 0.5 to 4 cm).
      All 14 tumors were of histological Furhman grade II/VI (n = 8) or Furhman grade
      I/VI (n = 6). All kidneys had pathologically confirmed negative margins. The mean
      age of the recipients was 40.8 +/- 9.2 years, with the majority being men (11
      men; 3 women). Median follow-up for this group was 69 months (range 14 to 200
      months). There have been no recurrences of tumor in these recipients and the 1-,
      3-, and 5-year patient and graft survivals are 100%, 100%, and 93%. CONCLUSIONS:
      These data represent the only data available (to our knowledge) on this issue.
      This experience indicates that donor kidneys with small, incidental RCC and low
      histological grade (Furhman grade I and II/IV) can be managed with excision and
      transplantation, with a low risk of tumor recurrence in the recipient.

PMID- 15848464
TI  - Central nervous system tumors in donors: misdiagnosis carries a high morbidity
      and mortality.
AB  - INTRODUCTION: The cost of misdiagnosis of central nervous system (CNS) tumors in
      donors has not been previously described. The purpose of this study was to
      examine the Israel Penn International Transplant Tumor Registry experience with
      these donors. METHODS: All cases where an error in diagnosis was made due to
      intracranial hemorrhage from undiagnosed CNS tumors and where CNS metastases were
      misdiagnosed as primary brain tumor were examined. RESULTS: Forty-two organ
      recipients with misdiagnosed primary brain deaths from 29 donors were examined.
      After transplantation these donors were identified with: melanoma (23%), renal
      cell carcinoma (19%), choriocarcinoma (12%), sarcoma (10%), Kaposi's sarcoma
      (7%), and variable tumors (22%). The majority of patients were renal allograft
      recipients (84%) followed by liver (n = 4) and lung recipients (n = 1). The most
      commonly diagnostic error was with intracranial hemorrhage (ICH) (62%). A donor
      related transmission rate of 74% (31/42) was identified among those patients with
      a misdiagnosed brain death. The majority of donor-transmitted cancers were
      identified in the recipient allograft (71%). Sixty-four percent of recipients
      suffered diffuse metastatic disease. Overall survival was poor, with a 5-year
      survival rate of 32% (10/31). Explantation was performed in 17 patients with
      confirmed donor-transmitted cancer, and in these patients a survival benefit was
      noted (10/17, 59%, vs 0/14, 0%; P < .01). CONCLUSIONS: Error in the diagnosis of
      donor brain death due to CNS tumors has significant and often fatal consequences.
      Allograft explantation for kidney recipients or retransplantation for extrarenal
      recipients may provide a survival benefit. Potential donors with unclear
      etiologies for brain death, particularly ICH, should be considered for a limited
      brain autopsy after donation.

PMID- 15848465
TI  - Excellent liver transplant survival rates under the MELD/PELD system.
AB  - The MELD/PELD (M/P) system for liver allocation was implemented on February 27,
      2002, in the United States. Since then sufficient time has elapsed to allow for
      assessment of posttransplant survival rates under this system. We analyzed 4163
      deceased donor liver transplants performed between February 27, 2002, and
      December 31, 2003, for whom follow-up reporting was 95% and 67% complete at 6 and
      12 months, respectively. Kaplan-Meier survival analysis revealed 1-year patient
      and graft survival rates for status 1 of 76.9% and 70.4%, respectively, and 87.3%
      and 82.9% for patients prioritized by M/P (P < .0001 for status 1 vs M/P). When
      adult candidates were stratified by MELD score quartile at transplant, 1-year
      survival rates were 89.5%, 88.3%, 86.6%, and 78.1% for lowest to highest quartile
      (P = .0002) and graft survival rates were similarly distributed (85.0%, 84.5%,
      82.7%, 73.0%, P < .0001). Candidates with hepatocellular cancer (89.6%) and other
      MELD score exceptions (88.8%) had slightly higher 1-year survival rates compared
      with standard MELD recipients (86.0%), which did not reach statistical
      significance (P = .089). Pediatric recipients had slightly better patient (88.7%)
      and graft (86.5%) survival rates at 1 year than adults but there were no
      significant differences among the PELD strata due to small numbers of patients in
      each PELD quartile. We conclude that patient and graft survival have remained
      excellent since implementation of the MELD/PELD system. Although recipients with
      MELD scores in the highest quartile have reduced survival compared with other
      quartiles, their 1-year survival rate is acceptable when their extreme risk of
      dying without a transplant is taken into consideration.

PMID- 15848466
TI  - The Dutch algorithm for allocation in living donor kidney exchange.
AB  - The shortage of kidneys from brain-dead donors for transplantation has made it
      necessary to look for alternatives. Living kidney donation is one possibility.
      However, because of ABO blood group incompatibility or immunological reasons,
      transplantation of kidneys from a living donor is not always possible. The seven
      Dutch kidney transplantation centers have developed a joint protocol for
      crossover, or paired donor exchange, kidney transplantation. To ensure a fair
      chance for all participating donor-recipient pairs, the Dutch Transplantation
      Foundation has developed an allocation algorithm to match compatible donor
      recipient pairs. A crossover match is performed every 3 months. The computer
      program developed by the Dutch Transplantation Foundation to match compatible
      donor-recipient pairs calculates the match probability (MP) of every potential
      recipient. The MP takes into account the peak panel-reactive antibodies (%PRA) of
      the recipient, the incidence within the crossover donor population of
      (compatible) ABO blood group, and HLA unacceptables of the recipient. The
      potential recipient with the lowest MP, in other words, the recipient with the
      smallest chance of finding a compatible donor in the pool, is ranked first. Until
      now, three matches have been performed in the Netherlands. A total of 53 pairs
      from all seven Dutch transplantation centers have participated. For 22 of the
      pairs a compatible donor-recipient pair was found.

PMID- 15848467
TI  - Gender imbalance in living kidney donation in Switzerland.
AB  - Gender characteristics were analyzed in 631 living kidney donors followed by the
      Swiss Organ Living Donor Health Registry (SOL-DHR) from 1993 to 2003; 65% of
      kidney donors were women and 64% of recipients were men. The proportion remained
      stable over the years and in different donor age classes from 25 to 74 years. The
      observed rate of female life partners giving their kidneys to male life partners
      was significantly higher than expected (P < .005). After exclusion of spousal
      pairs, the observed rate of gender pairing in all 4 possible directions differed
      significantly from the expected rate (P < .0001). Men were always behind the
      expected rate for kidney donation and women ahead. The main 3 reasons for gender
      imbalance in living kidney donors in Switzerland are the higher risk of men to
      acquire end-stage renal failure, financial risks for main breadwinners and the
      traditional female role in family life. Measures are proposed to narrow the gap
      between expected and observed gender balance in living organ donation.

PMID- 15848468
TI  - Efficiency is a legitimate consideration in equitable distribution of cadaveric
      transplants: development of an efficiency-equality model of equity.
AB  - It is proposed that equity is a trade-off, or compromise, between equality and
      efficiency. The kidney transplant allocation algorithm currently used in the
      United Kingdom (NAT) was tested in the efficiency-equity model. In an exercise of
      2000 past UK donors and a dynamic waiting list of 5000 potential recipients, 4000
      transplants were allocated according either by NAT, by equal allocation (EQ) (a
      lottery), or by efficiency (EF). Diabetic recipients received 7.4% of transplants
      in NAT, 8.6% in EQ, and 0% in EF; paediatric recipients received 6.8% in NAT,
      0.6% in EQ, and 0.7% in EF model. For HLA matching, there were 77.9% favourable
      or 000 matches in NAT, 3.0% in EQ, and 53.1% in EF. Predicted survival showed
      better outcomes in EF versus NAT (P < .0001) and in NAT versus EQ (P = .05). The
      NAT allocation system favours paediatric recipients and does not deny diabetics
      the chance of a transplant, broadly in line with published public and
      professional opinions. The NAT scheme achieves better HLA matching than the EF
      model, and this suggests that the rationale for allocation based primarily on HLA
      matching could be reexamined.

PMID- 15848469
TI  - Nonresident living kidney donors.
AB  - INTRODUCTION: The increasing number of immigrant residents has resulted in more
      foreign patients on the kidney transplant waiting list. While the willingness of
      their relatives to participate in a living kidney donation program is not
      different from that of relatives of autochthonous patients, many extra logistic
      and financial problems have to be solved, when the potential donor has to travel
      to Rotterdam. The fear of the authorities that the donor might stay in the
      Netherlands after donation is another hurdle. METHODS AND RESULTS: We analysed
      395 living kidney transplantations performed in Rotterdam from 1981 to 2003. In
      32 instances the donor came from abroad. Another 14 potential foreign donors came
      to Rotterdam but did not donate for various reasons. We calculated the costs for
      visa, travel, insurance, and loss of income. Total financial impact for the 46
      (potential) donors, amounted to capital JE, Ukrainian 56,604.09, which is capital
      JE, Ukrainian 1768.88 per actual performed donation. One kidney donor remained
      illegally in the Netherlands. CONCLUSION: We conclude that the efforts and
      support for foreign kidney donors to come to the Netherlands is justified and
      cost-effective. No evidence was found for a kidney donation immigration route.

PMID- 15848470
TI  - Kidney exchange programs: attitudes of transplant team members toward living
      donation and kidney exchanges.
AB  - INTRODUCTION: Several living donor kidney exchange programs (LDKEPs) have been
      established throughout the world; however, none have yet achieved the perceived
      substantial potential for increasing the number of living donor kidney
      transplants. Over the past 2 years, the Ohio Solid Organ Transplant Consortium
      (OSOTC) has developed and implemented an LDKEP with a complementary, robust web
      based computerized matching program for living donor/recipient pairs. Prior to
      implementation of the OSOTC LDKEP, attitudes of transplant professionals from
      each of eight participating kidney transplant programs were surveyed to
      determined attitudes toward living donation and LDKEP and to identify potential
      barriers to LDKEP. The state of decision making toward LDKEP was also examined.
      METHODS: Transplant professionals were surveyed using an instrument designed to
      assess attitudes toward living donation and LDKEPs. Most questions were answered
      on a Likert scale (1 = strongly agree, 5 = strongly disagree). RESULTS:
      Respondents agreed that living donor transplantation should be encouraged (mean
      1.17 +/- 0.6) and that the laparoscopic donor procedure was preferred (1.36 +/-
      0.82). Respondents had largely read about KEPs (2.02 +/- 1.02) but had "thought
      about participating in KEPs" (2.57 +/- 1.26), or actively sought information
      (2.87 +/- 1.3) to lesser degrees. Despite this, significant indecisiveness
      existed regarding participation in LDKEPs (2.73 +/- 1.39). CONCLUSIONS:
      Transplant professionals are highly aware of LDKEPs. However, they remain
      indecisive about LDKEP participation. These results indicate that barriers exist
      in the transplant community toward LDKEP, and these must be defined to increase
      LDKEP acceptance and participation.

PMID- 15848471
TI  - Influence of educational programs on perceived barriers toward living donor
      kidney exchange programs.
AB  - Living donor kidney exchange programs (LDKEPs) provide significant advantages
      toward addressing ABO and crossmatch incompatibility in living donor kidney
      transplantation, however, they have not yet realized their potential. The aim of
      this study was to examine the effect of an educational conference on perceived
      barriers toward living donor kidney transplantation and LDKEPs. METHODS: Between
      2002 and 2004, a state-wide living donor/living donor kidney exchange program was
      established by the Ohio Solid Organ Transplant Consortium (OSOTC). Prior to
      initiating the OSOTC LDKEP, an educational conference was held and its effect on
      transplant professional attitudes toward LDKEP barriers were assessed prior to
      and following the conference using a questionnaire. Questions were answered using
      a Likert scale (LS) (1 = strongly agree, 5 = strongly disagree). RESULTS: Forty
      eight participants completed questionnaires prior to and following the
      conference. The conference was judged to increase understanding of KEPs. The
      complementary web-based computer matching program was also felt to be an
      important component for the LDKEP. The conference did not affect the state of
      decision making regarding KEPs, however. Perceived barriers to LDKEPs not
      influenced by the educational conference included (1) concerns about donor travel
      costs, (2) concern about potential medical legal problems, (3) lack of perceived
      superiority of LDKEPs over desensitization protocols, and (4) concern about
      donation to strangers. Although numeric trends existed for each of these
      barriers, none were statistically significantly influenced by the education
      conference. CONCLUSIONS: These results suggest that interventions other than
      large scale educational conferences will be needed to address the barriers to
      LDKEP.

PMID- 15848472
TI  - Outcome of assessment of potential donors for live donor kidney transplants.
AB  - The critical shortage of cadaver donor organs for renal transplantation has
      resulted in the increased use of living donors. We reviewed the outcomes of the
      assessments of potential living kidney donors. One hundred seventeen potential
      donors evaluated over a 39-month period were included in the study. The work-up
      of the potential donors consisted of a step-wise progression of clinical, blood,
      and radiological tests. Of the 117 potential donors, only 20 were ultimately
      used. Five percent of the donors were found to be unsuitable because of medical
      problems at the initial visit. A further 25% were blood group incompatible, 13%
      were excluded following the investigations, 9% had psychosocial problems, and in
      4% there were recipient problems. Twenty-two percent of suitable donors were not
      used either because another live donor was used or because a cadaver donor kidney
      was available. In conclusion, although the assessment of potential donors
      requires much time and effort, only a small minority of donors assessed are
      ultimately used.

PMID- 15848473
TI  - Retroperitoneoscopic living donor nephrectomy: a comparison with the open
      approach in respect of early postoperative pain management.
AB  - INTRODUCTION: We retrospectively compared perioperative donor outcomes and early
      postoperative pain control after retroperitoneoscopic (RLDN) and standard open
      (OLDN) living donor nephrectomy. METHODS: One hundred donors included fifty after
      RLDN (37 women/13 men) and 50 after OLDN (35 women/15 men) were retrospectively
      analyzed for basic analgesics, for opioid consumption, and for visual analog
      scale (VAS) to verify the experienced pain. The donors were questioned in the
      morning and evening of the first through fifth postoperative days. RESULTS: The
      mean age of both groups was equal. The mean operating time was 149.7 +/- 48.2
      minutes (60 to 270) for RLDN and 164.1 +/- 30.3 minutes (60 to 240) for OLDN (P =
      NS). The mean warm ischemia time was 120 +/- 36 seconds (50 to 240) and 114 +/-
      31 seconds (60 to 190) for the RLDN and OLDN groups, respectively (P = NS). The
      mean evening VAS for RLDN versus OLDN on postoperative days 1 to 5 was: 2.1
      versus 2.2 (P = NS), 0.9 versus 1.8 (P = .009), 0.5 versus 1.3 (P = .016), 0.1
      versus 0.7 (P = .013), and 0.1 versus 0.7 (P = .013), respectively. In both
      groups there was a tendency toward a higher VAS score in the morning than in the
      evening. RLDN donors showed significantly earlier period free of pain (VAS = 0)
      than those after OLDN. There was a significant difference of being free from any
      opiate between both groups after surgery. CONCLUSIONS: After RLDN donors
      experienced less postoperative pain than after OLDN over the early postoperative
      days. Therefore, postoperative regional anesthesia is not necessary for donors
      operated by a retroperitoneoscopic approach.

PMID- 15848474
TI  - Telementoring facilitates independent hand-assisted laparoscopic living donor
      nephrectomy.
AB  - Laparoscopic living donor nephrectomy is a major advance but a challenging
      procedure to learn even after laparoscopic training. It requires significant
      previous training in both laparoscopic and transplant surgery. Telementoring has
      been shown to reduce the laparoscopic learning curve in other fields. Of six
      cases of hand-assisted laparoscopic (HAL) living donor nephrectomy at our
      institution, an on-site mentor supervised the initial two. We present the
      subsequent four cases as the first documented examples of telementored HAL live
      donor nephrectomy. Telelink was established with a Comstation (Zydacron, UK)
      incorporating a Z360 telementoring codec and four ISDN lines (512 kb/s) with time
      delay of 500 ms for both audio and video. The remote surgeon in Minnesota (USA)
      could change independently between the laparoscopic and external views. The
      operating surgeons were able to look at the mentor and converse with him
      throughout. There were no adverse events in recipients and graft function was
      excellent. With regards to the telementored group the mean operative time was 240
      minutes, the mean warm ischemic time 189 seconds, the mean estimated blood loss
      171 mL, and the mean length of hospital stay 3 days. Telementoring for
      laparoscopic donor nephrectomy is feasible, effective, and likely to aid
      independent practice by providing continued supervision and reducing the learning
      period.

PMID- 15848475
TI  - Retroperitoneoscopic living donor nephrectomy: a safe and minimally invasive
      procedure for the donor.
AB  - A living kidney donor surgery must be safe and minimally invasive. In addition
      the removed kidney must be in good condition. Retroperitoneoscopic nephrectomy
      has the advantage that it does not risk intra-abdominal organ injuries and
      provides direct access to the renal artery/vein despite the small working space.
      An abdominal wall-lifting method combined with the pneumoretroperitoneum provides
      sufficient space to use a hand skillfully in retroperitoneoscopic surgery.
      Introduction of hand-assisted retroperitoneoscopic living donor nephrectomy with
      the abdominal wall-lifting method yielded safer and easier operations as well as
      shorter warm ischemia (mean: 3 minutes; 7 seconds) and operative times (mean: 3
      hours; 28 minutes) in the current 10 cases. The procedure is a useful alternative
      to procure a kidney graft.

PMID- 15848476
TI  - Warm ischemic time during laparoscopic live donor nephrectomy: effects on graft
      function.
AB  - BACKGROUND: Laparoscopic live donor nephrectomy (LDN) has become established as a
      safe and effective alternative to the open procedure. However, the effect of
      prolonged warm ischemia time (WIT) during retrieval of the kidney remains
      unclear. The aim of this study was to analyze the effects of WIT on short-term
      and long-term graft outcomes after LDN. METHOD: In this retrospective analysis of
      LDN the effects of WIT on delayed graft function, rate of decline in serum
      creatinine concentration (SCr) in the first 10 days, changes in SCr at 3 months,
      acute rejection rate changes in Delta creatinine, biopsy-proved chronic allograft
      rejection and graft survival were assessed according to duration of WIT. Analysis
      was made by comparing WIT < or =3 versus >3 minutes and WIT <5, 5-10, and >10
      minutes. RESULTS: The WIT, which ranged from 1 to 15 minutes, appeared to be
      related to the learning curve and to technical difficulties. Prolonged WIT did
      not appear to have an effect on early graft function or the rate of decline in
      SCr during the first 3 months posttransplantation, but may be associated with an
      increased rate of acute rejection. Changes in Delta creatinine over time were not
      affected by the length of WIT during LDN. CONCLUSION: WIT encountered during LDN
      has no effect on either short-term or long-term graft outcome.

PMID- 15848477
TI  - Alterations in the practice of open and laparoscopic live donor nephrectomy at
      renal transplant centers in the UK and Ireland.
AB  - Live kidney donor (LKD) activity has increased over recent years. In response,
      the British Transplantation Society (BTS) has issued guidelines for best
      practice. This study involved two questionnaires sent to all renal transplant
      centers in the UK and Ireland to examine practice for the years 2000 and 2002.
      Findings were compared to BTS guidelines. There was a 100% response rate from 28
      centers for both years. Twenty-seven centers performed LKD in the year 2000,
      falling to 24 in 2002. Consultants reported 356 procedures in 2000, representing
      19% of all kidney transplants, and 403 in 2002, representing 23% of all kidney
      transplants. Three centers offered laparoscopic donor nephrectomy in 2000, and
      five did so in 2002. The majority of centers organize donor and recipient
      operations synchronously, and most have a consultant anaesthetist present for the
      donor procedure. There were variations in the use of thromboprophylaxis, and in
      donor follow-up. There is widespread practice of live kidney donation in the UK
      and Ireland, but BTS guidelines are not closely adhered to. Laparoscopic donor
      nephrectomy is offered at a small number of centers, but many have plans to
      introduce it.

PMID- 15848478
TI  - Laparoscopic donor nephrectomy yields kidneys with structure and function
      equivalent to those retrieved by open surgery.
AB  - The technical challenges of laparosopcic transperitoneal donor nephrectomy
      (LapDN) have raised concerns over the quality of the procured allografts. This
      study reports the anatomical and functional outcomes of kidneys retrieved from 60
      live donors entered into a randomized controlled trial of open versus
      laparoscopic procurement. Open and laparoscopic donors were well matched for age
      (P = .18) and body mass index (P = .49). Operating time (P = .0001) and first
      warm ischaemic time (P < .001) were longer for the laparoscopic donors but total
      warm time was not different (P = .52). Left renal vein length (P = .14) and left
      renal artery length (P = .38) were similar. No differences in right vessel length
      were observed. Rates of acute rejection did not differ, and recipient renal
      function was similar in the two groups. This study demonstrates that LapDN yields
      kidneys that are structurally and functionally equivalent to those acquired by
      the open operation. This data may go some way towards allaying concerns over the
      effect of laparoscopic procurement on live donor kidneys.

PMID- 15848479
TI  - A consecutive series of 70 laparoscopic donor nephrectomies demonstrates the
      safety of this new operation.
AB  - Laparoscopic donor nephrectomy (LDN) has the potential to overcome some of the
      disincentives to living kidney donation. This study presents the results of a
      consecutive series of 70 LDN from a single center with an emphasis on
      postoperative complication rates and donor recovery times. There was no selection
      bias based on donor body mass index or because of difficult vascular anatomy. All
      donors received postoperative analgesia using a patient-controlled system and
      returned to activities and employment at their discretion. There was no donor
      mortality and no episode of thromboembolic disease. One operation was converted
      from open to LDN because of renal artery bleeding. Postoperative complications
      encompassed chest infection (6%), unilateral pulmonary edema (3%), ileus (3%),
      wound infection (3%), paraesthesia of L1 (4%), testicular pain (3%), persistent
      wound pain (1.4%), and reoperation for division of adhesions (3%). In conclusion,
      LDN is a safe procedure with low postoperative morbidity. There were some
      unexpected complications, but recovery time was short.

PMID- 15848480
TI  - Laparoscopic living donor nephrectomy for kidneys with multiple arteries.
AB  - INTRODUCTION: Laparoscopic donor nephrectomy (LDN) involving kidneys with
      multiple arterial vessels is limited to a small number of reports, with all but
      two series reporting fewer than 25 patients. Moreover, outside of the pioneering
      centers at the University of Maryland and Johns Hopkins, no series of at least 25
      patients has been published confirming these experience. The present study
      presents the largest series of LDN of donor kidneys with multiple arterial
      vessels outside of these two pioneering programs. METHODS: All LDN performed at
      the University of Cincinnati from 2000 to 2004 were reviewed. Results between LDN
      kidneys with a single vessel and those with multiple vessels were compared.
      Statistical analysis included chi-square and Student t test. RESULTS: Of 240 LDN,
      37 were performed for kidneys with multiple vessels (15%): nine right kidneys
      (25%) and 28 left kidneys (75%). Cold ischemia time was longer for the multiple
      vessel organs (46 +/- 24 minutes) than for single vessel organs (35 +/- 13
      minutes; P = .001), and warm ischemia time was longer for the multiple vessel
      kidneys (4:20 +/- 2:05 minutes) than single vessel kidneys (3:13 +/- 0:47
      minutes; P = .001). Recipient renal function (serum creatinine) was similar for
      multiple and single artery donors at postoperative day 7 (1.76 +/- 1.38 and 1.7
      +/- 1.47) and at postoperative day 365 (1.06 +/- 0.3 and 1.34 +/- 0.44).
      CONCLUSIONS: This experience confirms results from other series in documenting
      the safety and reproducibility of LDN for kidneys with multiple arterial vessels.

PMID- 15848481
TI  - Laparoscopic right living donor nephrectomy.
AB  - INTRODUCTION: Left laparoscopic donor nephrectomy (LDN) is preferred over right
      LDN due to technical ease. The purpose of this study was to compare results
      between right and left LDN and thereby determine whether substantial experience
      with right LDN can provide results equivalent to left LDN. METHODS: All LDN from
      2000 to 2004 were reviewed, and right LDN data compared to left LDN data.
      Statistical analyses included chi-square and Student t tests. RESULTS: Two
      hundred thirteen left LDN (84%) were compared to 40 right LDN (16%). Donor age,
      gender, race, and body mass index, and multiple arteries were similar in right
      and left LDN groups. Operative and cold ischemia times were similar, but warm
      ischemia was longer for right LDN (3:55 +/- 1:22 minutes) than left LDN (3.18 +/-
      1:06 minutes; P = .004). Despite this, renal allograft function was similar on
      postoperative day 7 (creatinine 1.77 +/- 1.21 for right LDN, 1.7 +/- 1.5 for left
      LDN) and at 1 year (right LDN 1.5 +/- 0.4, left LDN 1.23 +/- 0.28). Graft
      survival rate in the right LDN at 1 year was 97.5%. CONCLUSIONS: This large
      experience with right LDN indicates that results comparable to left LDN can be
      obtained. This observation increases the options for LDN in patients with
      multiple left renal arteries, or with right renal cysts, or with right kidneys
      that are smaller in size compared to the contralateral left kidney.

PMID- 15848482
TI  - A controlled sequential evaluation of laparoscopic donor nephrectomy versus open
      donor nephrectomy: an update.
AB  - INTRODUCTION: In this study, we compared laparoscopic (lap Nx) to open donor
      nephrectomy (open Nx) with specific emphasis on outcomes in the donor and
      recipient. METHODS: This single-center sequential analysis recruited 100
      consecutive donor-recipient pairs operated on from 1997 until 2003. The open Nx
      (n = 30), were performed between 1997 and 2000; the lap Nx (n = 70) were
      performed between 2000 and 2003. Prospective records included operative data,
      anatomic details of the graft, hospital stay, and donor recovery. RESULTS: Donor
      characteristics and renal function were similar for open Nx and lap Nx. Operative
      parameters were similar except for the longer warm ischemia time in lap Nx versus
      open Nx (3.14 +/- 2.10 vs 1.5 +/- 0.5 minute, P < .001). Donor complications were
      equivalent in number, but differed in spectrum with a trend toward more
      intraoperative complications with lap Nx versus more postoperative complications
      for open Nx. Donor recovery, hospital stay, and return to work were improved in
      lap Nx versus open Nx (P < .001). Renal function of grafts after lap Nx were
      similar to open Nx: 2-year serum creatinine values of 1.26 +/- 0.21 versus 1.31
      +/- 0.40, respectively. Graft survivals were similar. CONCLUSION: Compared to
      open Nx lap Nx offers major advantages to the donor, and yields similarly
      favorable results in graft outcomes. However, it is more surgically demanding.
      Consequently, lap Nx should be adopted as the procedure of choice for living
      kidney retrieval.

PMID- 15848483
TI  - Technical modifications of laparoscopic donor nephrectomy: improved results with
      refinements in technique that mimic open nephrectomy.
AB  - INTRODUCTION: We have performed laparoscopic donor nephrectomy (lap Nx) since
      2000. In June 2002, we modified the technique to minimize the known disadvantages
      of ATN and delayed graft function. We review our series of lap Nx before and
      after introduction of these modifications, respectively. METHODS: Four technical
      modifications of lap Nx were introduced following the initial previously
      described 28 cases (Group I) and applied to the consecutive 42 cases described
      herein (Group II): (1) decreasing the intra-abdominal pressure from 15 mm Hg to 8
      mm Hg; (2) early dissection of the ureter and gonadal vein followed by vascular
      dissection (sharp and blunt using hydrodissection); (3) leaving the left gonadal
      vein in continuity with the left renal vein; and (4) early introduction of the
      Endocatch bag. RESULTS: Operative time was 276.6 +/- 67.1 min vs 210.0 +/- 38.0
      min for groups I and II, respectively (P = .04). Warm ischemia was 4.9 +/- 1.9
      min vs 1.5 +/- 0.9, min for groups I and II, respectively (P < .01). ATN occurred
      in 3/28 (10.7%) in group I vs 2/42 (4.8%) in-group II. There was one-vascular
      insult in the initial 5 Rt lap Nx, namely, transection of a segmental artery,
      that was reconstructed by bench repair without an impact on the outcome.
      Conversion was needed in 3/28 (10.7%) group I, but none of group II donors.
      CONCLUSION: The outcome of lap Nx can be significantly improved by applying
      technical modifications that simulate open Nx.

PMID- 15848484
TI  - Routine use of renal-dose dopamine during living donor nephrectomy has no
      beneficial effect to either donor or recipient.
AB  - BACKGROUND: The use of dopamine as a renoprotective agent in kidney
      transplantation remains unclear. Some reports suggest that dopamine improves
      initial graft function and survival, while others have failed to demonstrate a
      beneficial effect. Our live-donor nephrectomy program is serviced by 2 senior
      anesthetists, one who routinely uses dopamine and the other who considers that
      current evidence does not support a renoprotective effect of dopamine in
      laparoscopic donor nephrectomy. PURPOSE: We aimed to study the renoprotective
      effect on donor and recipient renal function of renal-dose dopamine during
      laparoscopic live-donor nephrectomy (LDN). METHODS: A retrospective analysis was
      performed of 59 live donor and recipient pairs between 1999 and 2004. Donors were
      grouped according to whether they received dopamine infusion during LDN. All
      donors received Hartmann solution to maintain the central venous pressure at 12
      mm Hg. The percentage change in serum creatinine (SCr) in both donors and
      recipients was compared at day 1, day 7, and week 6. RESULTS: In the donors,
      dopamine infusion had no effect on the mean percentage rise in SCr at day 1 or
      the mean percentage decrease in SCr at week 6. At day 7, however, patients who
      received dopamine had a significantly greater decrease in SCr compared with those
      who did not. In the recipients, there was no significant difference in the mean
      percentage decrease in SCr at days 1 or 7 or at week 6. Analysis at 1 year
      revealed no significant difference in sCr among the groups of donors and
      recipients. CONCLUSIONS: The intraoperative use of renal-dose dopamine during LDN
      seems to have no beneficial effect for either donor or recipient.

PMID- 15848485
TI  - New crossmatch technique eliminates interference by humanized and chimeric
      monoclonal antibodies.
AB  - Humanized and chimeric antilymphocyte antibodies (Ab) are used to prevent and
      treat rejection and for treatment of human disease. Rituximab (RIT, anti-CD20),
      daclizumab (DAC; anti-CD25), alemtuzumab (ALE; anti-CD52), or infliximab (IFX)
      may interfere with Ab detection methods such as complement-dependent cytotoxicity
      (CDC) and flow cytometric crossmatch (FCXM). These agents are recognized as anti
      human Ab or fix complement and are not differentiated from anti-allo-Ab. A new
      enzyme-linked immunosorbent assay crossmatch (XM) utilizing class I and II HLA
      antigens from donor cells called Transplant Monitoring System (TMS; GTI,
      Waukesha, Wisc) potentially precludes interference by eliminating non-major
      histocompatability complex antigens. To test this, normal sera (nonsensitized
      volunteers) were supplemented with 0.1 or 10 microg/mL of RIT, DAC, IFX or ALE,
      and were tested using three methods: the TMS T-cell CDCXM with antihuman globulin
      (AHG); and B-cell CDCXM without AHG; and FCXM with mean channel shifts of 45 and
      150 indicating positive T-cell and B-cell crossmatch, respectively. No reactivity
      occurred with normal sera using any crossmatch technique. At 0.1 and 10
      microg/mL, RIT interfered with CDC B-cell, but not T-cell crossmatch. RIT at 10,
      but not 0.1 microg/mL interfered with B-cell FCXM. No interference occurred with
      RIT in T-cell FCXM or TMS. ALE interfered with B-cell and T-cell CDC and FCXM but
      neither class I nor II TMS. DAC did not interfere with CDC or FCXM at 0.1
      microg/mL, but gave false positive B-cell FCXM and CDCXM with some samples. No
      interference by DAC occurred using TMS. TMS may be useful to differentiate de
      novo donor-specific Ab after treatment with humanized or chimeric Ab.

PMID- 15848486
TI  - Highly successful living donor kidney transplantation after conversion to
      negative of a previously positive flow-cytometry cross-match by pretransplant
      plasmapheresis.
AB  - Between July 2001 and November 2003, 16 patients with a positive flow-cytometry
      crossmatch to their potential living donor for kidney transplant were treated
      with desensitization protocol based on plasmapheresis and low-dose IVIg starting
      1 week before the scheduled transplant. Twelve patients (75%) converted to
      negative crossmatch and were successfully transplanted. Immunosuppression
      consisted of induction with thymoglobulin, tacrolimus, mycophenolate mofetil, and
      steroids. Plasmapheresis and IVIg were continued on alternate days for the first
      postoperative week. The 1-year patient and graft survival was 100%. The rate of
      acute rejection was 41% (16% cellular and 25% humoral). All of the rejection
      episodes resolved with treatment. Combination of plasmapheresis and IVIg allows
      successful conversion from positive to negative flow-cytometry crossmatch in 75%
      of cases; after conversion, kidney transplant can be carried out with a high rate
      of success.

PMID- 15848487
TI  - Are autoimmune diseases or glomerulonephritis affecting the development of panel
      reactive antibodies in candidates for renal transplantation?
AB  - Panel-reactive antibodies (PRA) are a major obstacle to kidney transplantation
      (KTx). It is not completely clear why only some patients develop PRA, whereas
      others do not. We hypothesized that other factors, such as autoimmune diseases
      involving the kidney, might be a trigger for PRA development. We reviewed the
      original diseases that led to renal failure and their possible role in PRA
      development. Charts of 270 patients on the active waiting list for KTx were
      reviewed for complete demographics, presence of PRA, peak PRA level, first KTx or
      retransplantation, original disease, blood transfusions, pregnancy and rejection.
      Patients were divided into group 1 (PRA >10%) and group 2 (PRA <10%). There was a
      significantly higher proportion of patients in group 1 with autoimmune diseases
      than in group 2. The same proportion was found significant for all of the
      patients as well as for the patients listed for the first KTx (new patients).
      Previous KTx has significant impact on both class I and II peak PRA levels when
      compared with new patients who are already sensitized. A subanalysis of
      retransplantation showed patients with autoimmune disease (54%) have more graft
      loss due to rejection compared with nonautoimmune disease (43%). There is an
      association between high PRA level and autoimmune diseases causing renal failure
      regardless of the previous KTx status. Besides the risk of recurrence, autoimmune
      disease seems to affect the risk of graft loss due to rejection.

PMID- 15848488
TI  - Synthesis of new and memory HLA antibodies from acute and chronic rejections
      versus pregnancies and blood transfusions.
AB  - BACKGROUND: This study compared HLA antibody (abs) production following acute
      (AR) and chronic (CR) rejection with HLA abs production following blood
      transfusions (TF) or pregnancies (P) among kidney and kidney pancreas transplant
      candidates. METHODS: Serum samples from 145 patients were screened for anti-HLA
      abs by flow cytometry using beads coated with purified HLA molecules. Among these
      patients, nine had lost their graft due to AR; 13, CR; six had been immunized by
      a single P; 20 by no more than two TF; 28 had no documented immunization; and 69
      had multiple immunizations. A Fisher exact test was used for the statistical
      analysis. RESULTS: Neither a single P nor a couple of TF by themselves immunized
      primary transplant recipients (P = .17, and P = .42, respectively). However,
      multiple P and TF together provided a potent immunogenic stimulus (P = .00001).
      In contrast, a single allograft loss induced a strong anti-HLA response (P = 1.03
      x 10(-8)). Following AR, anti-class I and II abs (P = .001), and following CR,
      anti-class II abs developed (P = .03). Waitlisted female candidates had
      significantly high PRA values than men (P = .00005), possibly because women had
      received significantly more immunizations than men (P = 4.0 x 10(-10)). SUMMARY:
      Patients are likely to produce both class I and II HLA abs following AR and only
      class II abs following CR. A couple of TF or a P may not be immunogenic; however,
      together they have great potential to sensitize female candidates. Perhaps that
      is why waitlisted women are far more immunized than waitlisted men.

PMID- 15848489
TI  - Management of end-stage renal disease patients with antiphospholipid antibody
      syndrome.
AB  - AIMS: End-stage renal disease (ESRD) patients with antiphospholipid antibody
      syndrome (APAS) remain at high risk for the development of posttransplant renal
      thrombosis without the benefit of anticoagulation therapy. This study describes
      the clinical management of these high-risk patients on anticoagulation therapy.
      METHODS: In this study period, 802 patients awaiting renal transplantation were
      screened for APAS. Twenty-seven of these patients (3%) had APAS. Of these 27,
      nine patients received cadaveric kidney transplants along with 409 patients who
      did not have APAS. Of the nine patients, seven were treated with coumadin and the
      remaining two were treated with heparin. RESULTS: Of the seven patients treated
      with coumadin, five did not have thrombotic complications posttransplant.
      However, three of these patients were taken off coumadin due to bleeding
      complications at 6 months to 1 year posttransplant. They all returned to dialysis
      shortly thereafter. The remaining two patients have maintained their allografts
      on coumadin therapy for 3 and 5 years posttransplants. The other two patients had
      posttransplant renal thrombosis within 24 hours of their transplant despite
      coumadin therapy. Of the two patients treated with heparin, one is doing well at
      6 years posttransplant while the other had early allograft loss due to
      thrombosis. CONCLUSIONS: ESRD patients with APAS may benefit from anticoagulation
      therapy; however, early allograft loss and bleeding complication are two serious
      side effects of this therapy.

PMID- 15848490
TI  - HCV core protein augments cyclosporine immunosuppression.
AB  - Hepatitis C viremia occurs universally after liver transplantation. It is
      speculated that soluble HCV proteins may be immunomodulatory. We measured the
      effects of HCV core upon human T-cell proliferation, expression of activation
      markers, and interaction with cyclosporine. Cells were activated with anti-CD3
      for 2-6 days. Cultivation with 1, 2, 4, and 8 microg/mL core reduced tritiated
      thymidine uptake by 7% (P = ns), 63% (P < .001), 69% (P < .001) and 92% (P <
      .001). Direct cell counting (10(4)) showed proliferative inhibition in treated
      cultures after 2 days (84%, P < .05), 4 days (93%, P < .05), and 6 days (88%, P <
      .05). Viability remained greater than 90%. Expression of activation markers was
      reduced with core treatment. Treatment with 4 microg/mL core for 2, 4, and 6 days
      reduced CD2+CD25+ by 67% (P < .05), 67% (P < .05), and 51% (P < .05) and CD2+DR+
      expression by 54% (P < .05), 46% (P < .05), and 54% (P < .05). Interaction
      between core and cyclosporine was determined by isobologram analysis which
      determines whether interactions are synergistic, additive or antagonistic.
      Combining core with cyclosporine resulted in an additive effect upon
      proliferative suppression. Linear regression confirmed an additive interaction
      with an r2 value of 0.98. The data shows that soluble core causes dose dependent
      suppression of T-cell proliferation and may potentiate suppression by
      cyclosporine.

PMID- 15848491
TI  - Vimentin antibodies: a non-HLA antibody as a potential risk factor in renal
      transplantation.
AB  - Chronic allograft rejection is the major problem encountered in solid organ
      transplantation and is the end point of several complex processes. A number of
      recent studies show both alloimmune and autoimmune responses may have roles to
      play. The importance of HLA antibodies in transplantation is well documented, but
      despite the introduction of very sensitive HLA screening assays, antibody
      mediated allograft rejection still occurs without detectable HLA antibodies. The
      target for antibody-mediated allograft rejection in these circumstances remains
      elusive, perhaps due to the variety of potential targets presented on endothelial
      cells. Recent studies identifying C4d and immunoglobulin deposits in patients
      undergoing late allograft loss provide evidence that chronic rejection involves
      humoral as well as cellular components. Several endothelial cell antigens that
      might be important in chronic rejection have been suggested, including MHC class
      I chain-related genes; Lewis; and the intermediate filament protein, vimentin.
      Vimentin is an ideal candidate antigen for antibody-mediated rejection as it is
      found in endothelial cells and is exposed to the immune system following surgery
      or by chronic allograft rejection due to endothelial cell breakdown, where the
      development of antibodies may cause further damage. We have developed a flow
      cytometric assay for the detection of antibodies to vimentin and have
      investigated whether HLA or vimentin antibodies are present in renal transplant
      recipients undergoing chronic rejection.

PMID- 15848492
TI  - Significant HLA matching effect in a large urban transplant center composed
      primarily of minorities.
AB  - In more than 1300 deceased donor transplants, including 75% Hispanics, African
      Americans, and Asians, a significant effect of mismatching (MM) was observed for
      zero to three MM compared to more than three MM (P < .02). There was a
      significantly better patient survival (P < .002), shorter hospital stay (P <
      .001), and a trend toward lowered immunosuppression. Zero to three MM were
      present in 48% of the recipient population in part due to the pre-UNOS algorithm
      that assigns points for zero MM and other MM grades. However, recently only zero
      MM receive points, therefore fewer zero to three MM recipients would be expected.
      The largest minority population is Hispanic. We postulated that at least part of
      the effect was associated with socioeconomic status and English as a second
      language parameters of our Hispanic population. Zero to three MM was found to
      decrease risk and should be used prospectively in minority donor/recipient
      combinations.

PMID- 15848493
TI  - An evaluation of HLA cross-reactive group matching on graft survival in deceased
      donor kidney recipients.
AB  - Since September 20, 1999, our organ procurement organization (OPO) serving an
      ethnically diverse local distribution area has allocated kidneys using a cross
      reactive group (CREG)-based variance. This variance awards 7 points for 0-CREG,0
      DR mismatches and 6 points for 0-A,B mismatches in addition to points given for
      waiting time (3) and panel-reactive antibodies (PRA) > or = 80% (3). Previously,
      we have shown that awarding points for 0-CREG,0-DR mismatches in kidney
      allocation improves the access to HLA-matched transplants for racial groups,
      especially for the black race. In this study, we evaluated if there are outcome
      benefits as well. One- and 3-year uncensored graft survival data and analyses for
      the influence of HLA mismatching on graft outcome in black and nonblack
      recipients were provided by Scientific Registry of Transplant Recipients (SRTR).
      Overall, 1-year graft survival was 87.4% and not significantly different for
      blacks (86.1%, n = 467) vs nonblacks (88.8%, n = 730); 3-year graft survival was
      74.6% and significantly lower P = .0001 for blacks (68.5%, n = 480) vs nonblacks
      (78.4%, n = 765). No significant advantage was observed for either the black or
      nonblack recipients in any of the HLA-mismatched categories, including the 0
      CREG,0-DR mismatch group. An HLA matching effect also was not seen when data were
      stratified for patients nonsensitized (PRA < or = 10%) and sensitized (PRA > 10%)
      at the time of transplantation, except for the improved graft survival in
      sensitized nonblack recipients of 0- A,B,DR-mismatched grafts. Of the patients
      who lost their grafts and returned to the waiting list for retransplantation, the
      0-A,B,DR mismatched were the least sensitized group (6%, n = 16), and there was a
      trend for less sensitization in the 0-CREG,0-DR-mismatched group (33%, n = 9),
      compared to those with other HLA mismatches (68%, n = 137). Thus, based on 1-year
      and 3-year follow-up data, there are no apparent graft outcome benefits for
      either CREG matching or conventional HLA matching in our service area, except for
      sensitized nonblack recipients receiving 0-A,B,DR-mismatched grafts. Such
      benefits may become more apparent with longer follow-up.

PMID- 15848494
TI  - The effect of renal transplantation on pulmonary function and respiratory muscle
      strength in patients with end-stage renal disease.
AB  - Pulmonary function and respiratory muscle strength was assessed in 29
      hemodialysis patients who underwent successful renal transplantation. These tests
      were performed 7 days prior to transplantation, 30 days following
      transplantation, and 90 days posttransplantation. Patients with end-stage renal
      disease showed dyspnea, a restrictive defect in pulmonary function, respiratory
      muscle weakness, and hypoxia. Following transplantation the dyspnea improved and
      mechanical indices of respiratory muscle function and lung volume improved. In
      conclusion transplantation resulted in a significant improvement in lung and
      respiratory muscle function.

PMID- 15848495
TI  - Pretransplant nephrectomy in patients with autosomal dominant polycystic kidney
      disease.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most
      common inherited kidney disease and a frequent cause of end-stage renal failure.
      Transplantation in patients with ADPKD is associated with specific cyst-related
      problems, especially urinary tract infections (UTI). Although pretransplant
      nephrectomy has been applied in this group of patients, evidence of the benefits
      of this strategy is lacking. Therefore, we compared the outcomes and
      posttransplant complications among patients with or without pretransplant
      nephrectomy. PATIENTS AND METHODS: ADPKD patients (73) transplanted from
      cadaveric donors were reviewed retrospectively with regard to posttransplant
      complications and outcomes. The groups either underwent pretransplant unilateral
      nephrectomy (n = 30) or were transplanted with native kidneys intact (n = 43).
      RESULTS: Two patients underwent simultaneous bilateral nephrectomy due to a large
      size of the polycystic kidneys interfering with the transplant operation. Overall
      postransplant complications were more frequent in the group without nephrectomy
      (34% vs 20%); however, the difference was not statistically significant. Most
      complications were related to cyst infections with 3 deaths (12%) due to lethal
      septicemia in the group without nephrectomy. No infection-related deaths were
      noted in the group with pretransplant nephrectomy. CONCLUSIONS: Graft and patient
      outcomes as well postransplant complications were similar in both groups,
      independent of previous nephrectomy. It seems that pretransplant unilateral
      nephrectomy should not be routine and has no advantage over transplantation with
      both native kidneys intact, although this conclusion is limited by the small
      number of patients. An Individualized approach should be applied especially when
      there has been a history of cyst-related infection.

PMID- 15848496
TI  - Standardized psychological evaluation pre- and posttransplantation: a new option.
AB  - A multicenter study was undertaken involving three teams in Italy to obtain a
      homogeneous psychological evaluation of patients needing organ transplantations.
      After a preliminary formulation of a common questionnaire individualizing 22
      items, yielding a final score from 0 to 44, 294 forms were analyzed for
      correlations between variables. The sample responses were related to individual
      variables as well as by cluster analysis to aggregate typical profiles.
      Clustering of variables was observed in three areas that showed two variables
      (no. 6, "ongoing psychotic disturbances" and no. 10 "drugs") to be separate. Area
      1 ("psychopathology") highlights psychic disturbances, cognitive disorders, and
      unhealthy behavioral styles; area 2 ("anxia") correlates anxious symptoms to
      pretransplant examinations and waiting time; area 3 ("depression") ties personal
      emotional resources and affective factors. Cluster analysis of the sample
      identified four groups: Group 1 (16.6%) "at risk;" mean score 25.2 (range 16-31);
      Group 2 (21.7%) "intermediate-at risk," mean score 32 (range 25-38); Group 3
      (29.6%) "intermediate-ideal," mean score 35.3 (range 26-40); and Group 4 (31.9%)
      "ideal candidate," mean score 40.7 (range 36-44). The two "intermediate" groups
      were studied for mean values for area 1; namely, a cut-off value of 1.78
      constituted a better or worse prognostic factor to assign the patient to either
      Group 2 or 3. Using a uniform method of psychological evaluation before
      transplantation reduced single operator subjectivity, obtaining comparable
      results in different transplant centers and allowing planning interventions for
      at-risk patients.

PMID- 15848497
TI  - Open-label, multicenter study on the safety, tolerability, and efficacy of
      Simulect in pediatric renal transplant recipients receiving triple therapy with
      cyclosporin, mycophenolate, and corticosteroids.
AB  - INTRODUCTION: Basiliximab is a monoclonal antibody directed to the interleukin-2
      receptor. Several studies have demonstrated both its efficacy and safety. Even
      with the use of polyclonal antibodies in renal pediatric transplant recipients,
      the local incidence of steroid-resistant rejections has been close to 10% of the
      total incidence of acute rejection episodes (AREs). An open, multicenter
      prospective study was performed to assess the safety tolerability, and efficacy
      of induction with basiliximab in renal pediatric transplant patients receiving
      cyclosporine, mycophenolate, and steroids. MATERIALS AND METHODS: Eighteen
      patients (8 boys) of mean age 11.9 +/- 4.5 years and body weight 32 +/- 15 kg
      received cadaveric (n = 7) or living (n = 11) donor grafts. Simulect was
      administered on days 0 and 4. Efficacy was assessed by the incidence of biopsy
      proven acute rejection (BPAR). Safety assessment consisted of a description of
      the adverse events (AEs). RESULTS: Six BPAR (Banff I and II) occurred in 5,
      (27.7%) children all of which were steroid responsive. Creatinine levels at day 7
      and months 3, 6, and 12 were 1.6 +/- 1.5 mg/dL, 1.0 +/- 0.4 mg/dL, 1.0 +/- 0.5
      mg/dL, and 1.0 +/- 0.4 mg/dL, respectively. Schwartz calculation at 12 months was
      71 +/- 15 mL/1.73 m2 AEs were hypertension (12), anemia (9), abdominal pain (8),
      metabolic acidosis (8), nausea (7), diarrhea (2), gingival hypertrophy (2),
      hirsutism (2), lymphocele (2), and infections (15). No deaths, graft losses,
      PTLDs, or malignancies were observed. CONCLUSIONS: No steroid-resistant AREs,
      were observed in this pediatric group using basiliximab. The Schwartz calculation
      at 12 months was 71 +/- 15 mL/min/1.73 m2.

PMID- 15848498
TI  - Long-term results of pediatric renal transplantation at one center in Turkey.
AB  - Kidney transplantation is more frequently indicated in children than in adults
      because growth retardation is an additional problem associated with chronic
      kidney disease in the pediatric age group. This study retrospectively analyzed
      the data from 75 kidney transplantations performed on 73 children (38 male and 35
      female) at a center in Turkey from late 1975 through 2003. The aim of the study
      was to investigate the case characteristics and the long-term outcomes in this
      patient group. Patient ages ranged from 8 to 16 years (mean, 14.9 +/- 2.2 years).
      Sixty (82.1%) children were on hemodialysis, and 12 (16.4%) on peritoneal
      dialysis prior to transplantation. Pre-emptive transplantation was performed for
      one (1.4%) patient. Fifty-nine transplantations used organs from live donors
      (78.7%) and 16 cadaver transplants (21.3%). The mean cold ischemia time for the
      cadaveric transplantations was 38.6 hours (range, 23-56 hours). All recipients
      were placed on a low-dose immunosuppressive regimen. One graft was lost due to
      hyperacute rejection. Twenty-one patients (28.8%) experienced a total of 24 acute
      rejection episodes. The follow-up period ranged from 1 to 190 months (mean, 44.1
      +/- 31.8 months). Concerning postoperative complications, four patients (5.5%)
      developed a lymphocele; there were two cases each (2.7% each) of distal ureteral
      stricture, perirenal hematoma, or renovascular stenosis; and one patient (1.4%)
      developed a urine leakage. Two patients (2.7%) developed Kaposi's sarcoma at 17
      and 3 months after transplantation. Six recipients died (mortality 8%), four of
      whom had a functioning graft. Two patients (2.7%) underwent retransplantation at
      4 and 2 years after the initial operation. The 1-, 3-, and 5-year graft survival
      rates for living-related transplantations were 92%, 81%, and 70%, and the
      corresponding patient survival rates were 98%, 93%, and 92%, respectively. The 1
      , 3-, and 5-year graft survival rates for cadaveric transplantations were 90%,
      78%, and 68%, and patient survival rates 98%, 91%, and 90%, respectively. These
      results indicate that kidney transplantation is successful in pediatric end-stage
      renal disease patients particularly from living-related donors.

PMID- 15848499
TI  - Predictive value of pretransplant inflammatory markers in renal allograft
      survival and rejection in children.
AB  - Pretransplant (pre-Tx) inflammation has been associated with acute rejection (AR)
      in adult Tx recipients. Our study was performed to determine whether a single pre
      Tx serum C-reactive protein (CRP), Neopterin (Neo), and IL-12 determination could
      predict outcome in pediatric renal Tx recipients. Pre-Tx sera from 51 children
      transplanted between 1985 and 2000 were analyzed for serum CRP, Neo, and IL-12
      for correlation with Tx-related variables. Endpoints were graft loss and AR.
      Kaplan-Meier and log-rank statistics were used to compare rejection-free and
      overall graft survival at different quartiles for each marker. Cox regression
      analysis was performed to determine the independent effects of various pre-Tx
      variables on the endpoints. The mean age of the children at Tx was 11 years. The
      mean CRP, Neo, and IL-12 were 1.3 mg/L, 1.78 ng/mL and 123 pg/mL, respectively.
      At last-follow-up (mean 4.9 years after Tx), 50% of the children had experienced
      AR and 29% had lost their grafts. The mean CRP, Neo, and IL-12 were not different
      between the patients with versus without AR or graft loss (P > .4 for all).
      Neither rejection-free survival nor graft survival was affected by CRP, Neo, or
      IL-12 quartiles (log-rank test). Cox regression analysis demonstrated no
      predictive value of any marker on the outcomes. Unlike adults, a single pre-Tx
      determination of inflammatory markers was not predictive of AR or graft loss in
      children. The pathogenesis of AR may be different in children with a lesser
      contribution of alloantigen-independent factors such as chronic infections.

PMID- 15848500
TI  - Sirolimus in pediatric renal transplantation.
AB  - Side effects of calcineurin inhibitors (CNIs) include nephrotoxicity and
      hypertension. Moreover, children have a higher risk of infections and
      posttransplantation lymphoproliferative disorders. We retrospectively evaluated
      the efficacy and safety of Sirolimus (SRL) in 18 patients, who were 10.52 +/-
      5.03 years at time of transplantation and received a CNI as the core
      immunosuppression. The most common indications for starting SRL therapy were
      chronic allograft nephropathy, Epstein-Barr virus-associated neoplasia, and
      thrombotic microangiopathy. The patients were converted to SRL at 49.14 +/- 45.9
      months posttransplantation. Mean follow-up after the switch to SRL was 13.83 +/-
      7.24 months. All patients who began SRL therapy remained on that medication. We
      observed a significant improvement (P < .05) in glomerular filtration rate
      assessed using the Schwartz formula at 3 months, which was sustained thereafter.
      There were no changes in proteinuria, plasma lipids, and platelet number.
      Although the prevalence of hypertensive patients decreased during follow-up, it
      was not significant. There was one steroid-sensitive, acute rejection episode.
      Serious adverse events included 1 death due to a relapse of B lymphoma, 1 sepsis,
      and 1 pancreatic pseudo-cyst. Adverse events were present in 17% of patients: 3
      Herpes Simplex infections, and 1 dose-related lymphedema. Further studies are
      necessary to assess the impact of adverse events in the pediatric transplant
      population receiving SRL as immunosuppression.

PMID- 15848501
TI  - Cadaveric kidney transplantation in children < or =20 kg in weight: long-term
      single-center experience.
AB  - BACKGROUND: We report long-term follow-up data on cadaveric kidney
      transplantation in children < or =20 kg in weight. METHODS: Between January 1990
      and October 2003, we performed 19 cadaveric renal transplants in 19 children < or
      =20 kg in weight. Mean age at transplantation was 4.7 years (range 18 months to 9
      years). Mean weight at transplantation was 14.4 kg (range 9 to 20 kg). Nine
      patients had preemptive kidney transplantation, whereas 10 were maintained on
      renal replacement therapy before the transplant operation. RESULTS: Actuarial 1-,
      3-, 5-, and 10-year patient survival rates were 89.5%, 89.5%, 89.5%, and 82%,
      respectively. Actuarial 1-, 3-, 5-, and 10-year graft survival rates were 79%,
      73%, 73%, 65%, respectively. Three patients died. Eight grafts failed. Cause of
      graft failure was death with a functioning graft in 3 patients, chronic rejection
      in 1, acute cellular rejection in 1, vascular rejection in 1, hemolytic-uremic
      syndrome in 1, and unknown in 1. CONCLUSIONS: Our results indicate the success of
      cadaveric kidney transplantation in the very small child with results comparable
      to living related donor transplantation.

PMID- 15848502
TI  - Twenty-five-year survival of living related kidney transplants: thirty-five
      years' experience.
AB  - AIM: Although better graft survival in patients treated with CsA has been
      obtained, chronic rejection continues to be a common complication in renal
      transplantation. In this study, we examined the graft survivals and complications
      among renal transplant patients followed for more than 25 years. METHODS: Between
      April 1970 and April 1979, 110 consecutive renal transplantations from living
      donors were performed in 110 patients. There were 83 men and 27 women of mean age
      of 27 +/- 7.0 years. A combination of azathioprine (AZ) and prednisolone (PSL)
      was used for the initial immunosuppressive therapy in all patients. RESULTS: Over
      25 years postoperatively, 41 patients died with or without a functioning graft
      due to complications including infections and malignancies. Therefore, the 25
      year patient survival was 62.5% and 34 patients returned to hemodialysis,
      yielding an actual 25-year graft survival of 36/110 (32.1%). The longest
      surviving graft is 30 years and 2 months. The main causes of death were
      infectious disease and malignancy; 73% of graft loss was due to chronic
      rejection. Mean serum creatinine of the patient with functioning grafts over 25
      years is 1.2 mg/dL; 75% of patients displayed a value under 1.5 mg/dL. The mean
      dosage of Az was 52.3 mg/d and PSL was 5.6 mg/d.

PMID- 15848503
TI  - Long-term graft outcome of living donor renal transplantation: single center
      experience.
AB  - The number of potential renal transplant recipients far exceeds the number of
      cadaveric donors. For this reason, living-related donors (LRD) and living
      unrelated donors (LURD) have been used to decrease the cadaveric donor shortage.
      We analyzed 571 living donor transplants for 25 years in our center. MATERIALS
      AND METHODS: From 1978 to 2003, 571 patients underwent LRD (n = 253), or LURD (n
      = 318) kidney transplantation. The patients were divided into precyclosporine era
      (from 1978 to 1987, n = 44; era I), cyclosporine era (from 1988 to 1997, n = 367,
      era II), and cyclosporine plus mycophenolate-mofetil era (from 1998 to 2003, n =
      160, era III). We compared the graft survival rate of the recipients according to
      the immunosuppressants, analyzing the variables of donor and recipient age, sex,
      HLA matching, and acute rejection rate. We also compared long-term survival rates
      between LRD and LURD. RESULTS: The 1- and 10-year graft survival rates of all
      patients were 93.4% and 77.4%, respectively. The 1- and 10- year graft survival
      rates were 75.0% and 36.3% in era I; and 94.8 % and 80.2% in era II. The 1- and 5
      year graft survival rates were 96.6% and 93.3% in era III (P < .001). The
      occurrence rate of an acute rejection episode was 11.4% (era I), 21.8% (era II),
      and 14.4% (era III) (P = .056). The 1- and 5-year graft survival rates were 92.3%
      and 81.7% among LRD transplants, and 94.2% and 86.9% among LURD transplants,
      respectively (P = .122). DISCUSSION: The graft survival rates of living-donor
      transplants are improving due to advances in patient care and new
      immunosuppressive agents.

PMID- 15848504
TI  - Sirolimus-based therapy with or without cyclosporine: long-term follow-up in
      renal transplant patients.
AB  - This open-label, phase 3b, extension trial in renal transplant recipients
      (Sirolimus Study 311) assessed the long-term safety of sirolimus (SRL)
      administered with cyclosporine (CsA) (SRL + CsA group, n = 98) or without CsA
      (SRL group, n = 69). Renal transplant recipients who had either completed one of
      seven previous SRL studies sponsored by Wyeth Research or had participated for >
      or =3 months and reached a protocol-designated endpoint were eligible for
      enrollment. Data were available for 167 patients, all of whom initially received
      steroids. Mean total SRL exposure was 1526 days, including previous study
      participation. After enrollment in the extension study, there were significantly
      more acute rejections in the SRL + CsA group (6.1% vs 0%, P < .05). Differences
      in rates of graft loss (3.1% vs 1.4%) and death (6.1% vs 1.4%) were not
      significantly different between SRL + CsA and SRL groups, respectively. At 48
      months after transplantation, calculated GFR (53.4 vs 70.9 mL/min) and hemoglobin
      (124.9 vs 136.6 g/L) were significantly better in the SRL group. Lipid values
      were not significantly different between groups at 48 months. The incidence of
      treatment-emergent increased creatinine, anemia, hypertension, headache,
      epistaxis, abnormal kidney function, and upper respiratory infection were
      significantly higher in the SRL + CsA group, whereas no adverse events were
      significantly higher in the SRL group. Malignancies were reported more frequently
      (11.2% vs 0%) with SRL + CsA. Results from this extension study indicate that SRL
      based therapy without CsA is a safe alternative to combination therapy with CsA,
      offering long-term improvement in renal function with no increased risk of late
      acute rejection.

PMID- 15848505
TI  - Transplantation of single pediatric kidneys into adult recipients.
AB  - AIM: To evaluate the outcome of single pediatric kidneys transplanted into adult
      recipients. METHODS: A retrospective single-center review was performed of
      transplants from donors less than 5 years of age. Outcomes were compared with
      recipients of grafts from donors 18 to 45 years transplanted during the same time
      period. RESULTS: Thirty single renal transplants from pediatric donors and 117
      transplants from adult donors between 18 and 45 years of age were performed
      during the study period. The mean age of the pediatric donors was 2.9 +/- 0.8
      years versus 31.5 +/- 8.9 years for adult donors (P < .001). The mean age of the
      recipients of pediatric donors was 41.9 +/- 13 years versus 48 +/- 12.6 years for
      recipients of adult grafts (P = .020). The mean recipient weight of pediatric
      donors was 55.9 +/- 7.8 kg versus 78.0 +/- 17.7 kg for recipients of adult donors
      (P < .001). Sixty-six percent of pediatric donor recipients were of female gender
      compared to only 36% of adult donor recipients (P = .005). Death-censored
      actuarial graft survivals at 1 and 4 years for recipients of pediatric donor
      grafts were 90% and 85% compared to 93% and 85% for recipients of adult donor
      grafts (P = NS). The mean calculated creatinine clearances of adult donor graft
      recipients at 1 and 4 years posttransplantation were 70.8 +/- 26.5 and 73.7 +/-
      27.2 mL/min, respectively, compared to 50.3 +/- 20.1 and 56.3 +/- 21.4 mL/min for
      pediatric donor grafts (P < .01 at 1 and 4 years). CONCLUSION: The use of single
      pediatric donor kidneys provides an excellent opportunity to safely expand the
      donor pool.

PMID- 15848506
TI  - Kidney transplants in African Americans and non-African Americans: equivalent
      outcomes with living but not deceased donors.
AB  - BACKGROUND: The outcome differences between ethnic groups after kidney
      transplantation have led to the characterization of African Americans (AA) as
      having high immune risk. Several multicenter clinical trials have reported better
      outcomes when AA receive higher doses of immunosuppression (I/S), suggesting
      pharmacokinetic (PK) and pharmacodynamic (PD) differences. However, the donor
      source has not been cited as an risk factor for outcome. METHODS: Patient and
      graft survival rates of 469 AA were compared with 308 non-African Americans (nAA)
      who received kidney transplants between January 1, 1995 and December 31, 2002,
      and were followed-up through December 31, 2003. Gender, age, and I/S protocol
      were not different between the groups. Based on outcomes, open and laparoscopic
      donor groups were combined for analysis. Deceased donor kidneys comprised 49% of
      the AA kidneys but only 32% of the nAA kidneys (P < .000). Kaplan-Meier survival
      statistics were used for both patient and graft survival. RESULTS: Patient
      survival rates for AA compared with nAA at 1, 3, 5, and 7 years were not
      statistically different for living (log rank statistic, 1 df, P = .56) versus
      deceased donor kidneys (log rank statistic, 1 df, P = .15). Kidney graft survival
      rates for AA compared with nAA at 1, 3, 5, and 7 years for living donor were
      similar (log rank statistic, 1 df, P = .493), but significantly different for
      deceased donor kidneys (log rank statistic, 1 df, P = .026). CONCLUSIONS: The
      majority of living donation occurred between ethnically similar donor-recipient
      pairs, whereas deceased donors tended to be nAA. The difference demonstrated by
      donor source suggests that antigens may be more dissimilar or uniquely different
      between ethnic groups.

PMID- 15848507
TI  - Reversibility from delayed hyperacute rejection in ABO-incompatible renal
      transplantation: histopathological findings of renal allograft biopsy.
AB  - ABO-incompatible renal transplantation (ABOIRTx) tend to lead to blood type
      antibody-mediated rejection, the so-called delayed hyperacute rejection (DHAR),
      which results in short-term graft loss. To clarify the accurate incidence and
      prognostic value of DHAR among ABOIRTx, we reviewed biopsy specimens obtained
      from ABOKTx allografts with abrupt dysfunction during the early period after
      transplantation. Among 74 ABOIRTx patients, 34 patients displayed allograft
      dysfunction within 14 days following transplantation. The biopsy specimens were
      classified based on the Banff schema. The pathological diagnosis of ABO blood
      type antibody-mediated humoral rejection (ABO-AMHR) was made by the following 3
      findings: Specimens with all of above-mentioned findings were categorized as
      severe ABO-AMHR; those with at least one findings, were categorized as mild ABO
      AMHR. All patients were treated with steroid pulse therapy and/or modification of
      other immunosuppressants. Group 1 consisted of severe ABO-AMHR (n = 6); group 2
      consisted of mild ABO-AMHR (n = 5); group 3 consisted of acute cellular rejection
      (n = 3); group 4 consisted of recovery phase of ATN (n = 11); group 5 consisted
      of calcineurin inhibitor toxicity (n = 2); and group 6 consisted of normal
      histology (n = 5). One of 6 patients (16%) in group 1 lost the graft because of
      DHAR irreversible by antirejection and anticoagulation therapy. However, there
      has been no clear definition of histpathological criteria for DHAR after ABO
      incompatible kidney transplantation. The definition must prognosticate whether
      the rejection process is reversible.

PMID- 15848508
TI  - Protocol biopsies in kidney transplant recipients: histologic findings as
      prognostic markers for graft function and outcome.
AB  - The aim of the present study was to identify subclinical and borderline
      rejections as well as histological markers of chronic allograft nephropathy (CAN)
      among protocol biopsies performed at 1 and 6 months after living related kidney
      transplantation to assess their possible implications for graft function. Twenty
      paired allograft biopsies performed at 1 and 6 months were reviewed according to
      the Banff scoring scheme. The mean ages of donors and recipients were 59.6 +/-
      13.8 and 34.4 +/- 8.7 years, respectively. Among all biopsies only 10% (4/40)
      showed no histopathological lesions. At the first month borderline rejection was
      shown in 35% and subclinical rejection in 10% of patients. At 6 months the
      proportion of findings was even higher, namely, 40% and 30%, respectively. When
      divided according to donor age, donors above 55 years showed a mean CAN score of
      2.33 +/- 1.56 which increased to 5.0 +/- 2.26 on the 6 month biopsy (214.3%).
      Unexpectedly, the proportion of these changes in the younger donor group also
      increased by 173.3%, which might have been explained by the greater number of
      borderline and subclinical rejections in the younger donor group at the 1 month
      biopsy. In conclusion, 1 month biopsy may be valuable to determine borderline and
      subclinical rejection and to prognosticate the outcome of renal allograft
      function. Our findings suggest a greater susceptibility of histological
      deterioration among the older donor population. However, the presence of an
      untreated rejection in the younger donor pool leads to a rapid impairment of the
      graft function accelerating the process of chronic allograft nephropathy.

PMID- 15848509
TI  - Baseline glomerular sclerosis influences morphological changes, but not level of
      serum creatinine.
AB  - The aim of this study was to investigate whether glomerular sclerosis (GS) at the
      time of engraftment affects subsequent morphology and clinical course of renal
      allografts. Eighty-one renal transplant recipients were recruited for this study.
      Protocol biopsies of the renal allografts were performed at engraftment, as well
      as at 1, 3, 5, and 7 years after transplantation. All cases were divided into 2
      groups based on the presence of GS at engraftment, namely, non-GS and GS groups.
      Morphological changes in the renal allografts were graded from 0 to 3+ based on
      the severity of chronic allograft nephropathy (CAN) of the Banff classification
      based on 5 factors: percentage of GS, extent of interstitial fibrosis, tubular
      atrophy, arterial intimal thickening, and arteriolar hyalinosis. Furthermore, the
      level of serum creatinine (s-Cr) at each year was examined by recipient age and
      gender, donor age and gender, type of donor (living/cadaver), delayed graft
      function, acute rejection within 1 year after transplantation, mean blood
      pressure, and use of calcineurin inhibitors as well as the presence of GS at
      engraftment. The extent of GS at engraftment significantly correlated with donor
      age (P = .0038) but with a weak correlation coefficient. Although the severity of
      CAN developed gradually in both non-GS and GS groups, differences in
      morphological changes at engraftment between the 2 groups persisted throughout 7
      years. Donor age and recipient gender influenced s-Cr significantly. In
      conclusion, the presence of GS at engraftment aggravates subsequent morphological
      changes and affects short-term but not long-term allograft prognosis.

PMID- 15848510
TI  - Renal biopsy donor group: the influence of glomerulosclerosis on transplant
      outcomes.
AB  - The UNOS donor population was examined from 1999 to 2002, and approximately 25%
      of the over 23,000 donors were biopsied (Bx). There was a significant trend (P <
      .001) of older donors, cardiovascular accident, and hypertension in the Bx group
      versus the non-Bx group. The percent GS was directly correlated (P < .001) to
      graft survival, delayed graft function, and primary nonfunction. Cox regression
      showed significant relative risk (RR) for >10% GS, hypertension, donors over the
      age of 50, and African American recipients. RR in donors with >10% GS could be
      ameliorated (P < .001) by choosing donors with <5 HLA-A, -B, or -DR mismatches
      (MM), or recipients who were nonsensitized, and/or first transplant. Risk should
      be managed in donors by choosing appropriate recipients and high-risk
      immunosuppresion protocols.

PMID- 15848511
TI  - Allograft glomerulitis: histologic characteristics to detect chronic humoral
      rejection.
AB  - The aim of this study was to clarify the histopathologic significance of
      allograft glomerulitis in chronic allograft nephropathy (CAN). Review of our
      renal allograft biopsy files revealed 140 specimens with CAN among 115 selected
      patients. They were classified into two groups: one had CAN with glomerulitis
      (group G), and the other was free of this finding (group NG). We evaluated the
      clinicopathologic parameters as follows: levels of serum creatinine and
      proteinuria in the biopsy; presence of circulating anti-donor antibodies;
      allograft failure rate; history of biopsy-proven acute cellular rejection (ACR)
      and acute humoral rejection (AHR); complications of ACR and chronic rejection
      (CR); and results of immunofluorescence studies for C4d and HLA-DR. The
      glomerulitis group showed a significantly greater incidence of CR complications,
      the presence of circulating anti-donor antibodies, and C4d deposition in
      peritubular and glomerular capillaries. This group also showed higher levels of
      serum creatinine and proteinuria, higher graft loss rate, and increased AHR
      incidence, although the differences were not significant. There was also no
      statistical significance in the HLA-DR expression on tubular epithelial cells.
      The present results strongly suggest that humoral factors may play an important
      role in the progression of glomerulitis in CAN. Therefore, we suspect that
      glomerulitis in CAN is one of the main histologic markers for CR. The presence of
      glomerulitis may represent humoral factor-dependent inflammation. It should be
      considered an important diagnostic criterion for CR in addition to double-contour
      formation and elastica disruptions with or without subendothelial inflammation
      (Banff '97).

PMID- 15848512
TI  - Does pretransplant obesity affect the outcome in kidney transplant recipients?
AB  - The effect of obesity on renal transplant outcome remains unclear due to
      conflicting published studies. The purpose of this study was to assess whether
      obesity affects the outcome in renal transplant patients. METHODS: We
      retrospectively analyzed 33 obese (BMI >30; mean = 34.1 +/- 3.68; group I) and 35
      nonobese (BMI < or = 30; mean = 23.6 +/- 3.18; group II) renal transplants
      performed at our center between March 1999 to December 2002. These two groups
      were well matched with respect to age, sex, donor source, hypertension, diabetes,
      ischemic heart disease, hyperlipidemia, native kidney disease (PCKD, 6 vs 4;
      diabetic, 5 vs 4; glomerulonephritis, 6 vs 7; FSGS, 2 vs 2 and IgA, 2 vs 7), HLA
      mismatch and immunosuppressants medications (Neoral, 21 vs 25; tacrolimus, 11 vs
      10; Cellcept, 28 vs 31; Prednisone, 33 vs 35; ATG, 7 vs 8; Basiliximab, 14 vs 13
      and Rapamycin, 5 vs 2, groups I and II, respectively). Follow-up was from 7
      months to 4.4 years. RESULTS: Significant differences were noted in operating
      time, wound infection, perinephric hematoma, lymphocele, and number of hospital
      days. There were no significant differences between the two groups in the
      incidence of wound dehiscence, deep vein thrombosis, pulmonary embolism,
      atelectasis, urine leak, delayed graft function, acute rejection rate, and the
      following posttransplant variables: diabetes mellitus, myocardial infarction,
      hyperlipidemia, hypertension, and incisional hernia. We conclude that obesity
      significantly increases operating time, wound complications, and
      hospitalizations.

PMID- 15848513
TI  - Renal transplantation in patients over 65 years of age: no more a
      contraindication but a growing indication.
AB  - INTRODUCTION: Worldwide organ shortage and the increasing age of end-stage renal
      disease patients demanding a graft have prompted extensive use of marginal
      donors. The "old-for-old" allocation has been proposed for the elderly. The aim
      of this study was to evaluate the results of a policy of free acceptance into the
      waiting list of recipients older than 65 years. METHODS: From 1987 to 2004 70
      patients whose mean age was 67.4 +/- 2.8 years, underwent an extensive
      pretransplant evaluation including cardiac studies. Immunosuppression was based
      upon low-dose steroids, and cyclosporine (50%) or tacrolimus (44%). RESULTS:
      Patient and graft survival at 1, 3, 5, and 10 years were 85%, 78.5%, 75%, 50%,
      and 80%, 74%, 70%, 36%, respectively. Death occurred in 17/70 (24%), 14 of whom
      had a functioning graft. The causes of death were 30% cancer, 23% cardiovascular,
      23% sepsis, 12% cerebrovascular hemorrhage, 12% meningitis. The acute rejection
      (AR) rate was 18.6%. The causes of graft loss were: 71% patient death, 4%
      irreversible AR, 4% vascular thrombosis, and 21% chronic allograft dysfunction.
      The main complications were: 52% prostatic hypertrophy, 40% urinary tract
      infections, 8.6% diabetes, 11% pneumonia, 10% cardiovascular diseases, 7%
      urological complications, 8% abdominal pathology, 6% acute pyelonephritis, 8% non
      skin cancer. CONCLUSIONS: Despite the increased vulnerability of the elderly,
      they should not be excluded a priori from renal transplantation. Extensive
      pretransplant screening, mainly cardiovascular, and a tailored immunosuppression
      are two crucial issues. The moderate rate of AR suggests that these patients do
      not have an impaired immunocompetence as far as acute rejection is concerned.

PMID- 15848514
TI  - The impact of gender and age matching for long-term graft survival in living
      donor renal transplantation.
AB  - In renal transplantation, donor age and allograft size are known to have an
      important influence on the outcome of the graft reflecting functional renal mass.
      Women tend to have smaller kidneys with 17% fewer nephrons than male kidneys. The
      number of glomeruli per kidney as well as the mean glomerular volume closely
      correlate with kidney weight and negatively correlate with subject age. We
      evaluated the impact of gender and age matching in living-donor renal
      transplantation on long-term graft survival. MATERIALS AND METHODS: Four groups
      were discerned among 614 renal transplants, according to donor and recipient
      gender: Group 1 was male donor to male recipient; Group 2 was male donor to
      female recipient; Group 3 was female donor to male recipient; and Group 4 was
      female donor to female recipient. We analyzed long-term graft survival and risk
      factors between the four groups as well as according to age matching. Statistical
      significance was determined by the Kaplan-Meier method and log rank test (P <
      .05). RESULT: The graft survival rates at 1, 3, 5, and 10 years were 92.62%,
      88.13%, 82.37%, and 76.07%, respectively. The risk factors affecting long-term
      graft survival were donor age, donor gender, acute rejection rate, and HLA-DR
      matching. Among the four groups, the graft survival rates of Group 3 (female
      donor to male recipient) were significantly different from the other groups (P =
      .0165). Also, the long-term graft survival rates according to age differences
      were significantly different between older donors than recipients and younger
      donors than recipients in each group (P = .0213). CONCLUSION: The importance of
      inadequate renal mass is magnified in high-risk recipients. Age matching could
      perhaps improve the results of transplantation, particularly when kidneys from
      older donors are used. Consideration of age and gender as criteria for the choice
      of donors and recipients may be considered in organ allocation.

PMID- 15848515
TI  - Significant differences in the efficacy of kidney transplantation between
      Hungarian Caucasians and Gypsies.
AB  - In a retrospective study we examined the differences between Caucasian (Group A)
      and Gypsy (Group B) renal allograft recipients transplanted in Hungary. From 1983
      to 2001, 1918 transplants were performed in Budapest (1825 Caucasian and 93 Gypsy
      recipients). Group B patients were younger (34 +/- 12 vs 42 +/- 14 years of age;
      P < .01) and Group A had more polycystic kidney disease (12% vs 3%; P < .025).
      Blood group B was more common in Group B (27% vs 19%; P = NS) than in Group A
      patients, and Group A had seemingly more diabetes (5% vs 1%; P = NS) than did
      Group B. There were no differences in HLA mismatches or panel reactive antibodies
      (PRA). No differences were seen in Group A vs Group B patient survivals at 1, 3,
      5, or 10 years' posttransplant (98% vs 95%; 90% vs 93%; 85% vs 88%; and 74% vs
      82%, respectively). However, Group A graft survivals were significantly better
      than Group B at 1, 3, 5, and 10 years' posttransplant (89% vs 77%; 82% vs 66%;
      76% vs 54%; and 57% vs 34%; each comparison P < .01). Group B recipients
      experienced a greater number of acute rejection episodes (66% vs 49%; P < .01),
      irreversible acute rejections (15% vs 6%; P < .001), chronic rejections (34% vs
      18%; P < .001), and graft loss due to immunosuppression noncompliance (5% vs 1%;
      P < .05) than did Group A recipients. As has been previously described for other
      non-Caucasian ethnic groups (eg, African-Americans), Hungarian Gypsies appear to
      be at a greater immunological risk for rejection and poorer long-term graft
      survival.

PMID- 15848516
TI  - Accurate prediction of kidney allograft outcome based on creatinine course in the
      first 6 months posttransplant.
AB  - Most attempts to predict early kidney allograft loss are based on the patient and
      donor characteristics at baseline. We investigated how the early posttransplant
      creatinine course compares to baseline information in the prediction of kidney
      graft failure within the first 4 years after transplantation. Two approaches to
      create a prediction rule for early graft failure were evaluated. First, the whole
      data set was analysed using a decision-tree building software. The software,
      rpart, builds classification or regression models; the resulting models can be
      represented as binary trees. In the second approach, a Hill-Climbing algorithm
      was applied to define cut-off values for the median creatinine level and
      creatinine slope in the period between day 60 and 180 after transplantation. Of
      the 497 patients available for analysis, 52 (10.5%) experienced an early graft
      loss (graft loss within the first 4 years after transplantation). From the rpart
      algorithm, a single decision criterion emerged: Median creatinine value on days
      60 to 180 higher than 3.1 mg/dL predicts early graft failure (accuracy 95.2% but
      sensitivity = 42.3%). In contrast, the Hill-Climbing algorithm delivered a cut
      off of 1.8 mg/dL for the median creatinine level and a cut-off of 0.3 mg/dL per
      month for the creatinine slope (sensitivity = 69.5% and specificity 79.0%).
      Prediction rules based on median and slope of creatinine levels in the first half
      year after transplantation allow early identification of patients who are at risk
      of loosing their graft early after transplantation. These patients may benefit
      from therapeutic measures tailored for this high-risk setting.

PMID- 15848517
TI  - Conversion of azathioprine to mycophenolate mofetil and chronic graft failure
      progression.
AB  - The purpose of the study was to evaluate the impact of conversion from
      azathioprine (AZA) to mycophenolate mofetil (MMF) on graft function in 35 renal
      transplant recipients with chronic allograft nephropathy (CAN). The
      immunosuppressive regimen originally consisted of AZA, cyclosporine (CsA), and
      prednisone (Pr). At the onset of the study (mean period = 39 posttransplant
      months), a graft biopsy was performed on all patients who were randomly divided
      into group 1 (n = 17) in whom MMF was introduced instead of AZA. The remaining 18
      subjects (group 2) were maintained on the previous regimen. Two periods were
      analyzed: period I: 12 months before, and period II: 12 months after biopsy and
      therapy conversion. Graft function was assessed monthly by measurements of the 24
      hour creatinine clearance (CCr). Analysis of variance (ANOVA) was used to compare
      the differences in CCr and proteinuria between the two groups. No difference was
      observed in the baseline characteristics, in the incidence of delayed graft
      function and acute rejection, or in the mean CsA dose. Pathohistological analysis
      revealed advanced CAN in the majority of patients in both groups. The
      morphological changes negatively correlated with graft function. The graft
      function showed parallel deterioration in the two groups; no significant
      difference was observed in the mean CCr values in the periods studied.
      Proteinuria was similar for both groups throughout the study. Conversion of AZA
      to MMF in recipients with CAN, albeit safe, was without significant benefit on
      the progression of chronic graft failure over the period of a year.

PMID- 15848518
TI  - Allogeneic hematopoietic stem-cell transplantation, mixed chimerism, and
      tolerance in living related donor renal allograft recipients.
AB  - OBJECTIVE: We designed a prospective, randomized, and controlled clinical trial
      to evaluate the efficacy and safety of achieving a mixed chimerism-associated
      tolerance protocol for recipients of living related donor (LRD) renal allografts.
      PATIENTS AND METHODS: Sixty-six consecutive patients were divided into two equal
      groups of 33 patients with end-stage renal disease. They were enrolled for
      transplantation after negative lymphocytotoxicity cross-matching (LCM). Both
      groups (treated [Tn] and control [Cn]) showed similar clinical and laboratory
      parameters and donor HLA match profiles. The Tn group underwent thymic
      transplantation of donor renal tissue, two donor-specific transfusions, low
      intensity conditioning, and high-dose hematopoietic stem-cell transplantation
      (HSCT) before renal transplantation. The conditioning regimen included low-dose,
      target-specific irradiation (to abdominal and inguinal lymph nodes, bone marrow
      [BM] from thoracolumbar vertebrae and part of the pelvis on alternate days, 100
      rad x 4), anti-T-cell antibodies (1.5 mg/kg body weight [BW]), cyclophosphamide
      (10 mg/kg BW x 2 consecutive days), and cyclosporine (CyA; >3 mg/kg BW/d).
      Unfractionated HSCT procured from the donor marrow was administered into the BM,
      portal and peripheral circulations, within 24 hours of achieving CD 4+/CD 8+ T
      cell count less than 10% of normal. This infusion was supplemented with a dose of
      peripherally mobilized stem cells (mean total dose of 20 x 10(8) cells/kg
      recipient BW) administered peripherally. Renal transplantation was performed
      after negative LCM. Donor-specific cytotoxic antibodies were eliminated with
      intravenous immunoglobulins and plasmapheresis before renal transplantation.
      Mixed chimerism was evaluated before and after transplantation at monthly
      intervals in patients with donors of opposite gender by the FISH technique. Both
      groups received CyA and prednisolone for immunosuppression; Cn subjects also
      received mycophenolate mofetil/azathioprine. Rejection was treated with standard
      treatment. Immunosuppression was withdrawn 6 months after renal transplantation
      for patients with consistently positive chimerism. Clinical tolerance was defined
      as stable allograft function for more than 100 days without immunosuppression and
      confirmed by allograft biopsy. RESULTS: Over a mean follow-up of 210 days, all Tn
      patients showed stable allograft function with mean serum creatinines (SCr) of
      1.20 mg/dL, no rejection/CMV infections/graft or patient loss. A low-level donor
      specific cytotoxic antibody was observed in all Tn patients. The CyA toxicity was
      noted in 10 (30.3%) patients. Persistent mixed hematopoietic chimerism was seen
      in all 21 patients irrespective of donor-recipient HLA matching (mean 0.5% before
      and 1 +/- 0.3% after transplantation). All four patients on drug withdrawal have
      shown donor-specific tolerance at a mean follow-up of 129.8 days. Other Tn
      patients are in the process of being weaned off immunosuppression. Mean SCr of
      controls was 1.45 mg/dL over a mean follow-up of 216 days. Acute rejection was
      observed in 17 (51.5%) patients; no CMV infection/patient loss was noted and one
      (3.03%) graft was lost in controls. No patient was lost in controls. No graft
      versus-host disease was observed in Tn patients. CONCLUSION: We have achieved
      mixed hematopoietic chimerism-associated tolerance with high-dose HSCT,
      intrathymic donor renal tissue transplantation, and minimal conditioning without
      any adverse effects.

PMID- 15848519
TI  - Demographic analysis and outcome features in a transplant outpatient clinic.
AB  - AIM: This retrospective report analyzed the demographic features of kidney
      transplant outpatients grafted in Turkey and in different regions of the world.
      METHODS: The patients were divided into 4 groups: Every cohort was subgrouped as
      either receiving a cadaveric (CT) or a live donor transplant (LT) performed in
      our institute (ICT, n = 147, ILT, n = 304), other institutions in Turkey (TCT, n
      = 16, TLT, n = 86), or in a foreign country (FCT, n = 66, FLT, n = 154). RESULTS:
      Among the patients with functional grafts, FLT transplantations, of which the
      vast majority were paid transplantations, constituted the second largest group (n
      = 105) following ILT (n = 214). In the ILT group, 5- and 10-year graft survival
      rates were 76% and 50%, respectively, and patient survival rates were 88% and
      78%, respectively. Considering the FLT group, 5- and 10-year graft survival
      figures were 70% and 42%, respectively, while patient survival rates in these
      periods were 81% and 69%, respectively. Patients with paid donor transplantations
      were characterized by a high risk of unconventional infectious complications in
      the early period, while midterm patient and graft survival was somewhat better
      than expected considering the high rate of complications in the early period.
      CONCLUSIONS: Paid organ transplantation should be discouraged. Organ donation
      should be stimulated by every means to avoid potentially fatal unconventional
      infections after transplantation from paid donors. If patients receive a paid
      transplant, however, they should be closely followed for these complications,
      since, if they survive the early period the midterm and long-term outcomes are
      quite reasonable.

PMID- 15848520
TI  - Immunomonitoring of renal transplant recipients in the early posttransplant
      period by sequential analysis of chemokine and chemokine receptor gene expression
      in peripheral blood mononuclear cells.
AB  - INTRODUCTION: We sought to determine whether sequential changes in chemokine
      ligand/receptor gene expression in the early posttransplant period of human renal
      allografts can be detected in peripheral blood mononuclear cells (PBMCs) and
      whether any such changes are predictive of clinical events. METHODS: Blood
      samples from 106 renal transplant recipients and 29 donor nephrectomy patients
      were taken preoperatively and daily for 14 days. Within the study period 22
      patients had biopsy-proven acute rejection. From each blood sample PBMCs were
      separated and gene expression levels for chemokines CCL3, CCL4, CCL5, CXCL10, and
      their receptors CCR1, CCR5, and CXCR3, were determined using real-time
      quantitative PCR. RESULTS: Different gene expression patterns were seen between
      the rejector and nonrejector groups with decreases in CCL4 and CCR5 expression on
      days 6 to 8 and increases in CCR1 expression on days 9 and 10 posttransplant.
      With CXCL10, decreases in expression were seen in the nonrejector group but
      increases were seen in the rejector group posttransplant. With data aligned to
      time of rejection diagnosis, statistically significant increases, that preceded
      the clinical detection of acute rejection were seen in CCR1 and CXCL10
      expression. Both their expression levels returned to pretransplant baseline
      values after successful antirejection therapy. CONCLUSION: We have demonstrated
      that changes in chemokine receptor/ligand gene expression by sequential
      monitoring in PBMCs can be detected in the early posttransplant period. In
      particular, CCR1 and CXCL10, which showed increased expression prior to rejection
      and returned to baseline levels with antirejection therapy, may have potential
      use in immunomonitoring and as predictive factors of rejection prior to its
      clinical manifestation.

PMID- 15848521
TI  - Granzyme B ELISPOT assay determines the cytotoxic T lymphocyte precursor
      frequency after HLA-identical living-related kidney transplantation.
AB  - A major goal in organ transplantation is to define the optimal immunosuppressive
      dose. Recently, we demonstrated that the frequency of cytotoxic T lymphocytes
      (CTLpf) identifies patients in whom the immunosuppressive load can be safely
      reduced. However, in peripheral blood mononuclear cells (PBMC) from HLA-identical
      living-related kidney transplant patients, no donor-specific CTLpf can be
      measured. The determination of the functional activity of cytotoxic T lymphocytes
      (CTLs) could be an alternative method for the CTLpf. Granzyme B (GrB) is present
      in the granules of CTLs and is involved in the direct lethal hit of donor target
      cells. Therefore, we wondered whether the GrB ELISPOT assay is an alternative
      method to determine the activity of CTLs after HLA-identical living-related
      kidney transplantation. We measured the number of GrB producing cells (pc)
      against donor PBMC and third-party PBMC in PBMC from HLA-identical patients who
      were reduced in their immunosuppression from 100% to 50% azathioprine with 5 to
      10 mg/day prednisone. We found low numbers of GrB pc before reduction of
      immunosuppression, as only 20% of the patients' PBMC responded to donor cells,
      whereas 57% of the patients' PBMC responded to donor cells after reduction of
      immunosuppression. After third-party stimulation, the number of GrB pc increased
      after tapering the immunosuppressive load (P = .03). Our results demonstrate that
      the GrB ELISPOT assay might be used as an alternative for the CTLpf after HLA
      identical living-related kidney transplantation.

PMID- 15848522
TI  - The influence of angiotensin-converting enzyme gene of donor and recipient on the
      function of transplanted kidney.
AB  - One of the genes that is supposed to influence renal graft function is the one
      encoding angiotensin I-converting enzyme (ACE). It shows polymorphism in the
      presence (I allele) or absence (D allele) of a 287-base pair fragment. The
      question arises whether ACE gene polymorphism of the recipient and donor
      influences renal graft survival. This prospective study included 94 recipients
      who underwent ACE genotyping (DD, DI, II) and measured their creatinine clearance
      after cimetidine administration. These factors were correlated with the
      occurrence of acute or chronic rejection and of pharmacologic treatment of
      hypertension. In 27 recipients it was possible to obtain the ACE genotype of the
      donor. Among the recipients, 36 proved to be DD genotype, 38 ID, and 20 II. Among
      the donors, 10 proved to be DD genotype, 10 ID, and 7 II. The changes in
      creatinine clearance after cimetidine administration were not significantly
      different among any of the genotype subgroups. Significantly higher creatinine
      concentrations were found among recipients with II genotype compared to the
      combined group of ID and DD among patients not treated with ACE inhibitors, but
      not among those receiving ACE I after kidney transplantation. No differences were
      found in the frequency of rejection episodes among the subgroups with different
      ACE genotypes. No significant influence of donor ACE genotype on renal graft
      function was observed. In summary, the I/D genotype was not an independent
      prognostic factor for renal graft survival in the first 4 years after
      transplantation. Possibly the use of ACE I alters the influence of genotype on
      some parameters.

PMID- 15848523
TI  - Cytokines and chemokine gene expression in human kidney transplantation.
AB  - Despite advances in immunosuppression in past decades, allograft rejection
      remains the main reason for kidney graft failure. Recently, despite great
      improvements in understanding of molecular basis of allograft rejections, renal
      histology remains the primary method to monitor the onset of graft rejection. The
      aim of the present study was to ascertain whether cytokine and chemokine
      expression profiles in kidney allografts contributed to the diagnosis of graft
      dysfunction. We analyzed mRNA expression in 174 kidney graft biopsies for the
      following cytokines: TGF-beta1, TNF-alpha, IL-10, and chemokine RANTES. Based on
      the expression levels obtained by real-time RT-PCR, we correlated data with the
      results of morphologic examinations. All tested cytokines and chemokines were
      upregulated (P < .001) during acute rejection compared to nonrejecting controls.
      Upregulation was also found in chronic allograft nephropathy (CAN) group for TGF
      beta1, IL-10 (P < .001), TNF-alpha, and RANTES (P < .01). Upregulated expression
      of IL-10 (P < .001), TGF-beta1, (P < .01) and RANTES (P < .05) showed borderline
      changes. Higher expression levels (P < .001) of TGF-beta1 and IL-10 were also
      found during ATN. IL-10 was upregulated (P < .01) in specimens with recurrent
      glomerulonephritis. Weakly increased (P < .05) expressions of TGF-beta1 were
      found during CsA toxicity. Distinctive expression levels between acute rejection
      and CAN were only found for IL-10 (P < .01). TNF-alpha showed a different
      expression profile in acute rejection versus ATN (P < .001). These findings
      suggest that distinct cytokine and chemokine expression profiles in grafts may
      contribute to the diagnosis for and elucidation of the immunopathologic process
      during graft dysfunction.

PMID- 15848524
TI  - Effect of cytokines and chemokines (TGF-beta, TNF-alpha, IL-6, IL-10, MCP-1,
      RANTES) gene polymorphisms in kidney recipients on posttransplantation outcome:
      influence of donor-recipient match.
AB  - Posttransplantation alloantigen-dependent and alloantigen-independent processes
      are both mediated by cytokines and chemokines. Recently cytokines and chemokines,
      as well as their receptors, have been shown to be highly polymorphic. The
      cytokine and chemokine gene polymorphisms are associated with variable
      production, activity, expression, or ligand-receptor affinity. The aim of our
      study was to analyze the relation between selected cytokine and chemokine gene
      polymorphisms in kidney donors and recipients as a function of donor-recipient
      match and posttransplantation outcome. Polymorphisms transforming growth factor
      beta (TGF-beta); tumor necrosis factor-alpha (TNF-alpha); interleukin (IL)-6, and
      IL-10; monocyte chemoattractant protein-1 (MCP-1); and RANTES (regulated upon
      activation, normal T-cell expressed and secreted) genes were determined using DNA
      polymerase chain reaction technology in 268 healthy volunteers, 345 kidney
      transplant recipients (1997 to 1999), and 298 cadaveric donors. Patients were
      followed up for 4 to 6 years. The distribution of alleles of selected genes was
      identical in control subjects, cadaveric donors, and recipients. Low TGF-beta
      production in both the donor and recipient genotypes was associated with risk for
      early rejection (6 months) and worse graft function at 4 years. The only tendency
      for worse graft outcome was observed among donor-recipient combinations
      mismatched for TGF-beta genotype. Genetic determination of TNF-alpha and IL-10
      production was associated with delayed graft function and rejection. IL-6 gene
      polymorphisms had no effect on the incidence of early acute rejections, but was
      associated with worse 5-year outcomes. Determinations of MCP-1 overproduction and
      RANTES-109 TT allele were associated with significant deterioration of graft
      function. Our data support the hypothesis that the strength of the alloimmune
      response after transplantation is in part genetically determined. Donor-recipient
      matching of cytokine gene polymorphisms has a marginal effect.

PMID- 15848525
TI  - Intragraft mRNA expression of cytokines and growth factors in human kidney
      allograft biopsies by in situ RT-PCR analysis.
AB  - The aim of our study was to correlate intragraft mRNA expression of cytokines and
      growth factors with histopathologic features in renal allograft biopsies. Fifty
      six core biopsies performed in 51 kidney transplant recipients were assessed by
      the Banff '97 classification. Tubular and glomerular expressions of IFN-gamma,
      TGF-beta1, and PDGF-B as well as IL-2, IL-6, and IL-10 mRNA were assessed using
      semiquantitative RT-PCR in situ. No significant differences were noted between
      acute cellular and vascular rejection with regard to the glomerular and tubular
      mRNA expression of cytokines examined. We observed a positive correlation between
      tubular and glomerular IL-10 and IFN-gamma mRNAs during acute rejection. In
      chronic rejection the mRNA expression levels of IFN-gamma and IL-2, IL-6, and IL
      10 did not differ from those of acute rejection; moreover, the glomerular
      expression of mRNA for TGF-beta1 (P < .05) and PDGF-B (P < .1) was even lower
      than during acute rejection episodes. Both tubular and glomerular IL-2, TGF
      beta1, and PDGF-B mRNA expression levels in biopsies with acute rejection were
      significantly higher than in acute tubular necrosis (ATN). Biopsy samples with
      borderline changes exhibited the lowest levels of cytokine gene expression and
      were close to the intensity of control specimens obtained from living donor
      kidney biopsies taken during organ harvest. Our data failed to show a dichotomy
      between Th1 and Th2 cytokine activation in biopsy specimens from kidney allograft
      recipients; both Th1- and Th2-derived cytokines were involved to similar extents
      in rejection processes.

PMID- 15848526
TI  - Mycophenolate mofetil but not the type of calcineurin inhibitor (cyclosporine vs
      tacrolimus) influences the intragraft mRNA expression of cytokines in human
      kidney allograft biopsies by in situ RT-PCR analysis.
AB  - The aim of the study was to assess the molecular background of the alloimmune
      response by the detection of low-abundance mRNA of cytokines in 34 core needle
      biopsies from kidney allografts with histopathological findings of acute
      rejection (AR). Recipients were immunosuppressed with a calcineurin inhibitor
      (CNI), cyclosporine or tacrolimus, and prednisone and azathioprine or
      mycophenolate mofetil (MMF). Tubular and glomerular expression of IL-2, IL-6, IL
      10, IFN-gamma, TGF-beta1, and PDGF-B mRNA were assessed using semiquantitative
      evaluations of RT-PCR in situ on paraffin tissue sections. This procedure
      resulted in light microscopy visualization of granular precipitates at the sites
      of the corresponding mRNA chains. The tubular expression of mRNA for IL-6 and TGF
      beta1 was significantly lower in biopsies with AR (n = 34) obtained from patients
      treated with MMF (n = 12) than in biopsies obtained from patients treated with
      azathioprine (n = 22) (P < .02). Responsiveness to corticosteroids tended to be
      more frequent among the MMF group (11 of 12 recipients vs 15 of 22 recipients, P
      = ns). Moreover, 8 of 12 recipients in the MMF-treated group displayed serum
      creatinine levels equal or less than 167 mmol/L 1 year after biopsy compared to 7
      of 22 recipients in the azathioprine-treated group. There was no significant
      difference between the groups that had or had not received corticosteroids or
      between those treated with each type of CNI. These results suggest stronger
      inhibition of humoral responses and down-regulation of fibrosis by MMF among
      recipients with AR.

PMID- 15848527
TI  - Serum TGF-beta1 correlates with chronic histopathological lesions in protocol
      biopsies of kidney allograft recipients.
AB  - INTRODUCTION: Transforming growth factor-beta (TGF-beta) is a well-known
      profibrotic factor playing a role in chronic kidney allograft nephropathy.
      Cyclosporine (CsA)-sparing immunosuppressive regimens may improve long-term graft
      function. Our aim was to study the influence of immunosuppressive treatment with
      versus without calcineurin inhibitors on serum TGF-beta levels and histological
      changes in protocol biopsies of kidney allograft recipients. PATIENTS AND
      METHODS: In this prospective, randomized study of 42 low-rejection risk patients
      we randomized two groups: group A: mycophenolate mofetil (MMF), prednisone,
      daclizumab, and reduced CsA dose for 7 months (5 mg per kg per day) followed by
      complete withdrawal (n = 21); and group B: normal CsA dose (10 mg per kg per day
      adjusted according to C2 levels), MMF, prednisone, and no daclizumab (n = 21).
      METHODS: In both groups we performed histological assessments (Banff 97) and
      measured serum TFG-beta levels before as well as, at 3 and 12 months after
      transplantation. RESULTS: We found a relationship between immunosuppressive
      regimen and the TGF-beta concentration over 1 year of observation. Before
      transplant the TGF-beta1 levels did not differ between the groups (P = .29); at 3
      months they were 33 +/- 9 vs 49 +/- 15 pg per mL, respectively, in groups A and B
      (P = .08), and at 12 months they were 39.5 +/- 4 versus 55.5 +/- 11 pg per mL,
      respectively, in groups A and B (P = .03). Protocol biopsies at 12 months in
      group B showed chronic tubular lesions more pronounced than in group A. TGF-beta1
      concentrations were significantly higher among group B than A. We conclude that
      TGF-beta1 concentration may predict the development of kidney graft fibrosis;
      early CsA withdrawal may achieve a reduction in chronic tubular and interstitial
      injury of cadaveric kidney allografts.

PMID- 15848528
TI  - Endothelial nitric oxide synthase and angiotensin II type 1 receptor gene
      polymorphisms can influence chronic inflammatory state in renal transplant
      patients.
AB  - Serum C-reactive protein (CRP) is a sensitive indicator of inflammation. Because
      increasing evidence shows the effect of endothelial nitric oxide synthase (eNOS)
      and the renin-angiotensin system on inflammation, we studied the association
      among chronic inflammation, chronic rejection, and gene polymorphisms of
      angiotensin II type 1 receptor (ATR1) and eNOS in renal transplant patients.
      METHODS: Data from 80 male and 35 female renal transplant patients (mean follow
      up, 60.6 +/- 22.2 months) were analyzed. Patients were grouped according to
      posttransplant CRP levels: group 1 patients (n = 46) had normal CRP levels (CRP
      <10 mg/L); group 2 had intermittent (n = 26), and group 3 had persistently
      elevated (n = 43) CRP levels. eNOS and ATR1 gene polymorphisms of the groups and
      the impact of posttransplant CRP response on development of chronic rejection and
      graft failure were analyzed. The bb allele of the eNOS gene was found in 74% of
      the patients, whereas 62% had AA allele of ATR1. RESULTS: Patients in group 1 had
      a significantly lower incidence of chronic rejection and graft failure when
      compared with patients in groups 2 and 3 (P = .05 and P = .02 respectively). The
      bb allele of the eNOS gene predominated in group 1 (P = .02); presence of non-AA
      allele of ATR1 1166 gene was found less frequently in group 3 (P = .01).
      CONCLUSIONS: The presence of the bb allele of the eNOS and non-AA allele of ATR1
      1166 gene is associated with an anti-inflammatory state and may predict renal
      outcome in transplant patients.

PMID- 15848529
TI  - Reduction of immunosuppressive load in renal transplant recipients with a low
      donor-specific cytotoxic T-lymphocyte precursor frequency is safe.
AB  - BACKGROUND: Tapering of immunosuppressive medication is indicated to prevent long
      term side effects. Recently, we have shown that renal transplant recipients can
      safely be converted from calcineurin inhibitors to MMF or AZA when their donor
      specific cytotoxic T-lymphocyte precursor frequencies (CTLpf) are below 10/10(6)
      PBMC. We wondered whether a low CTLpf also had predictive value when
      immunosuppressive medication was reduced in patients only on MMF or AZA and
      steroid medication. METHODS: Renal transplant recipients with stable renal
      function at least 2 years after transplantation and with low (<10/10(6) PBMC)
      CTLpf were included. Their MMF or AZA dose was reduced to 75% and to 50% of the
      original dose at 4 months and 8 months after inclusion. Endpoint of the study was
      12 months after inclusion or developing acute rejection. RESULTS: Forty-five
      patients have reached the 1-year follow up endpoint. Their median time after
      transplantation was 4.2 years (range 2.0-15.5 years). Acute rejection was seen in
      one patient only (who had discontinued all his medication). CONCLUSION: In
      patients with low CTLpf long after kidney transplantation, a 50% reduction of
      immunosuppression is safe and further decreasing their immunosuppressive load is
      the obvious next step.

PMID- 15848530
TI  - Expression of CD158b on peripheral blood lymphocytic cell after kidney
      transplantation.
AB  - OBJECTIVE: To investigate the expression of CD158b on peripheral blood
      lymphocytes after kidney transplantation. METHODS: Sixty two kidney transplant
      patients were divided into two groups (normal group and rejection group)
      according to pathologic results and clinical situation. Blood samples were
      assessed for percentage of CD3+; CD19+; CD3-CD16/56+; CD3+CD158b+; CD19+CD158b+,
      and CD3-CD16/56+CD158b+ subsets. RESULTS: The percentages of CD3+ cells preop as
      well as at 1 and 7 postoperative and the day acute rejection happened were 60.06
      +/- 4.67, 40.43 +/- 4.11, 31.67 +/- 4.04, and 39.21 +/- 5.20, respectively. The
      percentages of CD3-CD16/56+ were 21.65 +/- 1.79, 33.84 +/- 5.45, 38.10 +/- 4.86,
      and 39.53 +/- 4.80, respectively. The percentages of CD3+CD158b+ were 1.46 +/-
      0.31, 1.88 +/- 0.70, 2.03 +/- 1.04, and 0.65 +/- 0.12, respectively. The
      percentages of CD3-CD16/56+CD158b+ were 5.87 +/- 1.24, 3.57 +/- 0.57, 2.82 +/-
      0.45, and 1.60 +/- 0.33, respectively. CONCLUSIONS: The percentage of CD3+ cells
      in the normal and the rejection groups decreased significantly. The percentages
      of CD158b+T cells decreased significantly after acute rejection. The percentage
      of CD158b+NK cells decreased significantly after kidney transplantation,
      decreasing gradually after acute rejection. The percentage of CD158b+ total T
      cells decreased significantly following acute rejection. The percentage of CD3
      CD16/56+CD158b+ of total NK cells decreased significantly after kidney
      transplantation and after acute rejection. Because few factors interfere with the
      expression of CD158b on NK cells, monitoring of this marker may be accurate and
      sensitive.

PMID- 15848531
TI  - Long-term evolution of lymphocytes subsets after induction therapy based on
      continuous versus discontinuous administration of anti-thymocyte globulins in
      renal-transplant patients.
AB  - The aim of our retrospective study was to assess the long-term evolution of
      lymphocyte subsets after two modes of administration of anti-thymocyte globulin
      (ATG) after renal transplantation. METHODS: Before 1993, patients (group I, n =
      93) received fixed doses of RATG (1 mg/kg per day) for 8 consecutive days.
      Thereafter, RATG was either continued at the same dose for 15 days, in cases of
      delayed graft function, or was infused every other day at the same dose until the
      serum creatinine level became <150 micromol/L. After 1993, patients (group II, n
      = 66) received RATG at full dose (1 mg/kg per day) during the first 3 days and,
      thereafter, doses were adapted to target a CD2 T-cell count <50/mm3. RATG
      cumulative dose was significantly higher among group I than group II (9.7 +/- 4.5
      versus 7.4 +/- 3.2 mg/kg, P = .0002). RESULTS: In both groups, total lymphocyte
      and T lymphocyte subset (CD4, CD8, CD2, CD3) counts decreased significantly
      during the first month after transplantation, increasing slowly between the first
      month and the third year posttransplantation. Thereafter it rose rapidly, which
      was greater in group II. At last follow up, total lymphocyte, T lymphocyte
      subsets and NK cell counts were similar to those observed before transplantation.
      At all monitoring times, T lymphocyte, B lymphocyte, and NK cell counts were
      similar in both group, except for the total lymphocyte count at 6 months and CD4
      T lymphocyte count at 1 year, which were significantly higher in group II
      compared to group I. CONCLUSION: Induction therapy based on continuous or
      discontinuous administration of ATG is associated with profound depletion of T,
      B, and NK cells during the first 3 years, followed by a progressive
      reconstitution of the lymphocyte pool after 5 years.

PMID- 15848532
TI  - A randomized trial of steroid avoidance in renal transplant patients treated with
      everolimus and cyclosporine.
AB  - In this randomized trial renal transplant recipients were treated with
      basiliximab, everolimus 3 mg/day, low-dose CsA. At transplantation, patients were
      randomized to stop steroids at the seventh day (group A) or to continue oral
      steroids in low doses (group B). Of the 113 patients enrolled, 65 were randomized
      to group A and 68 to group B. All patients were followed for 2 years. During the
      study 28 (43%) group A patients required reintroduced corticosteroids. One
      patient died, in group B. The Graft survival rate was 97% in group A and 90% in
      group B. There were more biopsy-proven rejections in group A (32% vs 16%; P =
      .044). The mean creatinine clearance was 54 +/- 21 mL/min in group A vs 56 +/- 22
      mL/min in group B. Mean levels of serum cholesterol tended to be lower in group
      A, but the difference was of borderline significance (191 +/- 91 vs 251 +/- 188
      mg/dL; P = .07). Vascular thrombosis (0 vs 5) and pneumonia requiring
      hospitalization (2 vs 7) tended to be more frequent in group B. Only three cases
      of CMV infection (1 vs 2) occurred. An immunosuppressive therapy with everolimus
      and low-dose CsA allows one to obtain excellent renal graft survival and stable
      graft function at 2 years. Early interruption of steroids in patients treated
      with this regimen may increase the risk of acute rejection, but neither affects
      graft survival nor graft function, while possibly reducing the risk of
      hyperlipemia and vascular thrombosis. About 60% of patients given everolimus and
      low-dose CsA can definitively stop steroids after 1 week.

PMID- 15848533
TI  - Comparative study of clinical outcome in kidney transplantation between early
      steroid withdrawal protocol using basiliximab, calcineurin inhibitor, and
      mycophenolate mofetil and triple regimen consisting of calcineurin inhibitor,
      mycophenolate mofetil, and steroid.
AB  - AIMS: Effect of early steroid withdrawal protocol using basiliximab in kidney
      transplantation (KTx) on the clinical outcomes was investigated as compared with
      triple regimen. METHODS: Kidney transplant patients in group 1 (n = 62) were
      treated with 8 mg/kg of cyclosporine (CsA), 2000 mg of MMF, two bolus IV
      injections of 20 mg of basiliximab and 500 mg of methylprednisolone (MP) rapidly
      tapered and withdrawn at 14 postoperative days (POD). Group 2 (n = 56) was
      treated with same dose of CsA and MMF, and 250 mg of MP tapered and continued.
      Acute rejection (AR) episodes were treated with MP pulse therapy followed by
      muromonab CD3 (OKT3) in case of steroid-resistant rejection. RESULTS: In 46 of 62
      cases (74.2%) in group 1, steroid was successfully withdrawn at 13.7 +/- 1.7 POD.
      Graft survival at 3, 6, and 12 months in group 1 was 100%, 100%, and 98.4% (one
      death with functioning graft), and 100%, 98.2%, and 96.4% in group 2,
      respectively. The incidence of AR was 12.9% for group 1 and 42.9% for group 2,
      among which 21 cases in group 2 were treated with ALG or OKT3; no patient needed
      ALG or OKT3 in group 1. Fifteen cases in group 1 and 13 cases in group 2
      developed CMV antigenemia, among which febrile episode was exhibited in 3 cases
      (4.8%) in group 1 and 5 cases (8.9%) in group 2. CONCLUSIONS: Early steroid
      withdrawal protocol using basiliximab is promising for reducing the incidence of
      AR (especially steroid-resistant rejection), CMV diseases, and steroid-related
      complications.

PMID- 15848534
TI  - Corticosteroid avoidance ameliorates lymphocele formation and wound healing
      complications associated with sirolimus therapy.
AB  - INTRODUCTION: Sirolimus (RAPA) and corticosteroids (CS) both inhibit wound
      healing. To evaluate the possibility that RAPA and CS have additive effects on
      wound healing, we evaluated the effects of corticosteroid avoidance (CSAV) on
      wound healing complications in patients treated with RAPA. METHODS: One hundred
      nine patients treated with a CSAV regimen (no pretransplantation or
      posttransplantation CS) were compared with a historical control group (n = 72)
      that received cyclosporine (CsA), mycophenolate mofetil (MMF), and CS. The CSAV
      group received low-dose CsA, MMF, RAPA, and thymoglobulin induction.
      Complications were classified as follows: wound healing complications (WHC) or
      infectious wound complications (IWC). WHC included lymphocele, hernia,
      dehiscence, diastasis, and skin edge separation. IWC included wound abscess and
      empiric antibiotic therapy for wound erythema. RESULTS: The CSAV group was
      largely CS-free: 11% of patients received CS for rejection, 12% of patients
      received CS for recurrent disease, and 85% of patients are currently off CS. The
      CSAV group had a significantly lower incidence of WHC (13.7% vs 28%; P = .03) and
      lymphoceles (5.5% vs 16%; P = .02) than the control group. There was no
      difference in the incidence of IWC between the 2 groups. Patients who received
      CSAV were 18% less likely (P = .57) to develop any type of complication, 41% less
      likely (P = .20) to develop a WHC, and 71% less likely (P = .018) to develop a
      lymphocele. CONCLUSIONS: CSAV in a RAPA-based regimen results in a marked
      reduction in WHC and lymphoceles. Therefore, CSAV provides a promising approach
      for addressing WHC associated with RAPA therapy.

PMID- 15848535
TI  - Early corticosteroid withdrawal under modern immunosuppression in renal
      transplantation: multivariate analysis of risk factors for acute rejection.
AB  - Early corticosteroid withdrawal has been shown to be effective in low-risk
      patient populations in a number of US and European multicenter trials. However,
      patient populations traditionally considered to be at high risk for acute
      rejection (eg, African Americans, repeat transplant recipients, sensitized
      patients) are usually excluded from these trials. Since our initial experience
      with early withdrawal almost 10 years ago, we have included high-immunologic-risk
      patients. We have accumulated enough high-risk patients with early withdrawal to
      allow the first multivariate analysis of risk factors for acute rejection in
      early withdrawal under modern immunosuppression. METHODS: Early withdrawal was
      performed under prospective IRB-approved protocols. Statistical analysis included
      chi square test and logistic regression. All rejection episodes were biopsy
      proven and graded by Banff 1997 criteria. RESULTS: A total of 164 patients
      underwent early withdrawal: 82% had at least one mismatched DR antigen, 17% had
      delayed graft function, 33% were African American, and 18% were repeat transplant
      recipients. Multivariate analysis of risk factors for acute rejection indicated
      that two factors induced a statistically significant alteration in acute
      rejection risk: repeat transplant recipients (4.3-fold increased risk) and
      thymoglobulin induction (0.30 risk (ie, 70% reduction in risk compared to
      patients not receiving thymoglobulin induction). Sensitized recipients and
      African Americans were also at increased risk but did not quite reach statistical
      significance. These data strongly support the use of T-cell depleting antibody
      induction therapy in high-risk patients undergoing early withdrawal under modern
      immunosuppression.

PMID- 15848536
TI  - Body weight alterations under early corticosteroid withdrawal and chronic
      corticosteroid therapy with modern immunosuppression.
AB  - Weight gain is a well-known complication of corticosteroid maintenance therapy.
      The purpose of our study was to compare patterns of weight gain under chronic
      corticosteroid therapy (CCST) to those observed under early corticosteroid
      withdrawal (CSWD) in renal transplant recipients. METHODS: Renal transplant
      recipients who underwent early CSWD in IRB-approved prospective trials were
      compared to a historical control group of patients receiving CCST who were
      matched for age, sex, and race. RESULTS: One hundred sixty-nine patients with
      early CSWD were compared to 132 patients who received CCST. Mean population
      weight gain was significantly higher in CCST patients at 12 months (5.52 kg vs
      3.05 kg, P < .05) posttransplant. Caucasian CSWD patients demonstrated a greater
      reduction in weight gain with CSWD than African Americans (mean weight decrease
      2.9 vs 1.9 kg/patient, P < .05). Patients who were overweight (body mass index
      [BMI] 25-30) or obese (BMI > 30) demonstrated a greater reduction in weight gain
      with CSWD at 1 year (mean reduction in weight gain with CSWD 5.3 kg/patient and
      4.4 kg/patient) than did patients of normal weight (BMI < 25; 0.1 kg/patient, P <
      .01 and <.05 versus BMI < 25). CONCLUSIONS: Early CSWD patients gain
      significantly less weight than CCST patients following transplantation. Marked
      variations in the effect of early CSWD on weight gain may be observed due to race
      and pretransplant BMI. Caucasians and overweight patients demonstrate greater
      benefits from CSWD than African Americans and patients with normal BMI.

PMID- 15848537
TI  - A prospective, pilot study of early corticosteroid cessation in high-immunologic
      risk patients: the Cincinnati experience.
AB  - BACKGROUND: The first prospective trial of steroid withdrawal dedicated to high
      immunologic-risk patients is reported herein. METHODS: Twenty-five patients were
      enrolled prospectively in an IRB-approved HIPAA-compliant protocol.
      Immunosuppression included corticosteroid withdrawal (CSWD) at 7 days, tacrolimus
      (target trough level 4 to 8 ng/mL), sirolimus (target trough level 8 to 12
      ng/mL), and Mycophenolate Mofetil (2 g/d). Induction with daclizumab (2 mg/kg) on
      posttransplant days (PTD) 0 and 14 was administered to the first 10 patients. The
      protocol for the next 15 patients was modified because of high acute rejection
      rates to include received T-cell-depleting antibody induction therapy with
      thymoglobulin (1.5 mg/kg) on PTDs 0 and 2 followed by daclizumab on Postoperative
      day (POD) 14. Recipient inclusion criteria included: (1) repeat transplant
      recipients; or (2) patients with a peak PRA > or =25%. All rejection episodes
      were diagnosed by biopsy and graded using Banff '97 criteria. RESULTS: Twenty
      five patients were enrolled and median follow-up was 402 days. Forty percent of
      recipients were black, 68% of patients were repeat transplant recipients, 68%
      received deceased donor kidneys, and 36% had a peak flow PRA >25%. Overall acute
      rejection, graft survival, and patient survival rates of 40%, 88%, and 96%,
      respectively, were observed for the duration of the study. Acute rejection
      occurred in 6 of 10 patients (60%) with daclizumab induction; however, acute
      rejection rates fell to 27% when thymoglobulin was introduced (P = .1).
      CONCLUSIONS: This study supports our previous observations in a multivariate
      analysis of early CSWD patients, wherein polyclonal antibody induction therapy
      reduced acute rejection. High-immunologic-risk patients may be able to undergo
      early CSWD with acceptable rates of acute rejection.

PMID- 15848538
TI  - A prospective, randomized, multicenter, double-blind study of early
      corticosteroid cessation versus long-term maintenance of corticosteroid therapy
      with tacrolimus and mycophenolate mofetil in primary renal transplant recipients:
      one year report.
AB  - This report summarizes year 1 blinded data from a 5-year prospective, randomized
      (1:1, stratified by race and donor type), multicenter, double-blind study
      comparing treatment failure rates between early cessation of corticosteroid
      therapy and long-term corticosteroid maintenance therapy in 397 primary renal
      transplant recipients receiving tacrolimus and mycophenolate mofetil with
      antibody induction. Sixteen (4.1%) patients died or experienced graft loss during
      year 1 (9 deaths, 6 graft losses, and 1 death with a graft loss). Fifty-nine
      (15.3%) patients experienced rejection; 40 (10.4%) of these cases were biopsy
      confirmed. Values for 10-year predictive risk of coronary heart disease (CHD)
      estimated from the Framingham Heart Study scores showed a shift from baseline
      toward a more favorable risk profile. Renal transplant recipients treated with a
      tacrolimus-based immunosuppressive regimen and either early cessation or
      maintenance of corticosteroid therapy experienced excellent patient and graft
      survival, low acute rejection rates, low rate of posttransplantation diabetes
      mellitus (9.0%), and improved CHD risk profile at 1 year posttransplantation.

PMID- 15848539
TI  - Histocompatibility testing predicts acute rejection risk in early corticosteroid
      withdrawal regimens.
AB  - Histocompatibility testing has been shown to predict acute rejection risk in
      steroid-based immunosuppression. However, little evidence exists of its ability
      to predict acute rejection risk in corticosteroid-free patients, with no evidence
      in early corticosteroid withdrawal (CSWD) under modern immunosuppression. The
      purpose of this study was to evaluate the ability of histocompatibility testing
      to identify patients at high risk for acute rejection after early CSWD. METHODS:
      One hundred eighty-one patients were entered into six IRB-approved early CSWD
      regimens. Histocompatibility testing included serologic PRA, flow cytometric PRA
      testing by Class I and Class II MHC beads, and B cell crossmatching with pronase
      treatment. All rejection episodes were biopsy proven, and grading was assigned
      using Banff criteria. Influence of individual tests was examined using Chi square
      univariate and multivariate logistic regression analysis. RESULTS: Median follow
      up was 23.5 months (range 7-48 months). Of 181 patients, 16% were repeat
      transplant recipients, 36% received deceased donor renal transplants, 48%
      received living related donor renal transplants, and 16% received living
      unrelated transplants. Overall patient survival was 97%, and death-censored graft
      survival was 96.5%. Acute rejection rates in the entire follow-up period were
      17.7%. 12.4% in primary transplant recipients and 37% in repeat transplant
      recipients. Multivariate analysis revealed that HLA AB and DR locus mismatching
      were associated with increased acute rejection risk. Similarly, serologic PRA
      analysis predicted acute rejection risk; however, flow cytometry crossmatching
      did not predict acute rejection risk. The greatest single influence on acute
      rejection risk appeared to be a flow cytometric B cell crossmatch (7.94-fold
      increased risk). In conclusion, histocompatibility testing can identify patients
      at high risk for acute rejection following early CSWD. HLA matching, serologic
      PRA testing, and flow cytometry-based B cell crossmatching can all be used to
      predict acute rejection risk.

PMID- 15848540
TI  - Global cardiovascular risk under early corticosteroid cessation decreases
      progressively in the first year following renal transplantation.
AB  - A primary reason to eliminate corticosteroids from immunosuppressive regimens in
      solid organ transplant recipients is improved cardiovascular risk profiles.
      Although a number of studies have documented that corticosteroid withdrawal
      (CSWD) regimens reduce hypertension, hyperlipidemia, diabetes, and weight gain,
      global assessments of cardiovascular risk under CSWD have not been reported. The
      purpose of this study was to document cardiovascular risk under CSWD using a
      global risk assessment by Framingham risk assessment. METHODS: Framingham global
      cardiovascular risk assessments were performed at baseline and 3, 6, and 12
      months posttransplant on patients enrolled in prospective, IRB-approved early (<7
      days of corticosteroids) CSWD trials. Framingham score was based on age, sex,
      presence of diabetes, HDL and total cholesterol, and systolic blood pressure. All
      patients were nonsmokers. Left ventricular hypertrophy assessment by EKG criteria
      was not available at all time points and therefore were not included. RESULTS:
      One hundred eighty-three patients were included in the analysis. Fourteen percent
      of patients had evidence of coronary heart disease (prior MI, CABG, PTCA, or
      significant cardiovascular disease as evidenced by angiography) prior to
      transplant. Complete information was available for 160 patients at baseline, 132
      at 1, 3, and 6 months, and 93 at 12 months posttransplant. Mean 10-year risk
      (expressed as percent) for developing coronary heart disease decreased over time:
      8.03 at baseline, 8.31 at 3 months, 7.40 at 6 months, and 7.20 at 12 months,
      indicating that global cardiovascular risk fell at 1 year posttransplant by about
      10% in renal transplant recipients undergoing early CSWD. CONCLUSIONS: Estimation
      of cardiovascular risk by Framingham risk factor assessment allows incorporation
      of several cardiovascular risk factors into a single estimate, thereby accounting
      for differential effects of each individual factor on global cardiovascular risk.
      This experience indicates that global cardiovascular risk decreases by
      approximately 10% at 1 year posttransplant in renal transplant recipients who
      undergo early corticosteroid withdrawal (CSWD).

PMID- 15848541
TI  - African American renal transplant recipients benefit from early corticosteroid
      withdrawal under modern immunosuppression.
AB  - African Americans have historically been considered high-risk renal transplant
      recipients due to increased rejection rates and reduced long-term graft survival.
      Modern immunosuppression has reduced rejections and improved graft survival in
      African Americans and may allow successful corticosteroid withdrawal. Outcomes in
      56 African Americans were compared to 56 non-African Americans enrolled in early
      withdrawal protocols. Results are reported as African American versus non-African
      American. Acute rejection at 1 year was 23% and 18% (P = NS), while patient and
      graft survival was 96% versus 98% and 91% versus 91% (P = NS), respectively. In
      conclusion, early withdrawal in African Americans is associated with acceptable
      rejection rates and excellent patient and graft survival, indicating that the
      risks and benefits of early withdrawal are similar between African Americans and
      non-African Americans. Additional followup is needed to determine long-term renal
      function, graft survival, and cardiovascular risk in African Americans with early
      steroid withdrawal.

PMID- 15848542
TI  - Early steroid withdrawal does not increase risk for recurrent focal segmental
      glomerulosclerosis.
AB  - Experience with early corticosteroid withdrawal (CSWD) in renal transplant
      recipients with focal segmental glomerulosclerosis (FSGS) has not been previously
      reported. Since corticosteroids are used to treat primary FSGS, concern exists as
      to whether early CSWD regimens will be associated with an increased risk of FSGS
      recurrence posttransplant. The purpose of the present study was to evaluate the
      results of early CSWD in FSGS recipients and compare these results to a historic
      control group of FSGS patients who underwent renal transplantation under
      corticosteroid-based immunosuppression. METHODS: Forty-three patients with FSGS
      underwent renal transplantation with early CSWD. Results in these patients were
      compared to FSGS patients that underwent renal transplantation with chronic
      corticosteroid therapy. All rejection episodes were biopsy proven with grading by
      Banff criteria. Statistical analyses included Student's t test and chi square
      tests. RESULTS: Results in 43 patients with a median follow-up of 569 days were
      analyzed and compared to control patients. There was no significant difference in
      recurrent FSGS, time to recurrence, or graft loss. CONCLUSION: CSWD does not
      increase risk for recurrence of FSGS. These observations indicate that ECSW can
      be achieved in FSGS patients, thereby affording them the benefits of steroid
      elimination.

PMID- 15848543
TI  - Effect of race on the occurrence of posttransplant diabetes in kidney transplant
      recipients treated with early steroid discontinuation.
AB  - INTRODUCTION: Early steroid discontinuation (within 5 days after transplant) has
      been associated with a lower incidence of posttransplant diabetes mellitus
      (PTDM). A retrospective study was done to assess the incidence of PDTM in
      relation to racial groups in kidney transplant recipients who received early
      steroid discontinuation. METHODS: Between January 2002 and January 2004, 125
      consecutive, primary adult kidney transplant recipients (51 cadaveric donor, 74
      living donor) were performed at the University of Illinois at Chicago. The first
      34 recipients were treated with steroid maintenance therapy, while the remaining
      91 underwent early steroid discontinuation. Group A (n = 91) had steroids
      discontinued on postoperative day 6 and maintenance immunosuppression consisting
      of tacrolimus and mycophenolate mofetil. Group B (n = 34) received the same
      immunosuppression but was maintained on steroids indefinitely. Induction
      consisted of Thymoglobulin in African-Americans; all others received Simulect.
      RESULTS: At 1 year, patient and graft survivals were similar in both groups;
      there was a trend for reduction of acute rejection rates in group A (4% vs 12%).
      The incidence of PTDM was significantly lower in group A (7%) compared to group B
      (26%; P = .0209). The incidence of PTDM in group A was limited to Hispanic
      patients. African-Americans and Caucasians in group A did not experience PTDM (P
      = .005 compared to African-Americans in group B). CONCLUSION: A steroid-free
      protocol virtually eliminated the incidence of PTDM in African-Americans and
      Caucasians but had no effect on the development of PTDM in Hispanic recipients.
      Alternative immunosuppression may benefit this population.

PMID- 15848544
TI  - Rabbit antithymocyte globulin: a postoperative risk factor for sirolimus-treated
      renal transplant patients?
AB  - AIMS: Randomized controlled studies suggest an increased incidence of
      perioperative wound complications among sirolimus-treated renal transplant
      patients. The present study analyzed the effect of rabbit antithymocyte globulin
      (rATG) on these postoperative complications. METHODS: Four hundred and twelve
      renal transplants were performed and managed postoperatively at two University
      affiliated hospitals between January 1, 2001, and December 31, 2003. The patients
      received corticosteroids and Sirolimus, with delayed introduction of cyclosporine
      when the serum creatinine had decreased below 2.5 mg/dL. Two groups of patients
      were discriminated: group 1 received Basiliximab 20 mg on day 0 and day 4 (n =
      283); group 2 recipients with a high panel of reactive antibody (PRA > 20%) and
      retransplant patients received rATG for induction (n = 129) for a maximum of 2
      weeks postoperatively. The incidence of rejection was 14.5% for group 1 vs. 8.5%
      for group 2 patients. To avoid confounding variable associated with the rejection
      treatment, any patient with rejection was excluded for statistical analysis, as
      were patients with follow- up less than 30 days. The final study group for
      analysis included 350 patients: 235 with Basiliximab induction (group 1) and 115
      rATG induction (group 2). The mean follow-up was 21.8 +/- 11 months. Differences
      in the incidences of postoperative hernia, wound infections, or lymphoceles
      requiring any form of drainage were analyzed for statistical significance using
      the chi-square test. RESULTS: The percentage of patients with wound complications
      was 26.0% versus 39.1% (P < .025) for group 1 versus group 2, respectively.
      Incisional hernias occurred in 10.6% versus 18.3% patients (P < .05), wound
      infections in 11.1% versus 16.5% (P = NS), and lymphoceles in 10.6% versus 15.9%
      (P = NS) for the two groups, respectively. CONCLUSIONS: rATG-induced renal
      transplants recipients treated with sirolimus, cyclosporine, and steroids show a
      significantly increased incidence of postoperative incisional hernias and a trend
      toward a greater number of lymphocele and wound infection complications.

PMID- 15848545
TI  - Addition of sirolimus to cyclosporine in long-term kidney transplant recipients
      to withdraw steroid.
AB  - The aim of this study was to evaluate the feasibility of a steroid-free
      maintenance immunosuppression regimen in long-term renal transplant (KTx)
      recipients after addition of sirolimus (SRL) to cyclosporine (CsA)-based
      immunosuppression. A multicenter, prospective pilot study of steroid withdrawal
      (SW) was initiated for KTx patients. SW was divided into three phases: (A)
      conversion to a SRL + CsA + steroid regimen; (B) steroid tapering and withdrawal;
      and (C) maintenance with SRL + CsA. Primary endpoints of the study were incidence
      of acute biopsy-proven rejection (AR) and safety. In the A and B phases of the
      study 42 KTx patients (132 +/- 75 months post-Tx) were entered into the study, 18
      of 42 (43%) with severe, acute side effects due to the CsA + SRL combination.
      These side effects were reversible with reduction of CsA or with suspension of
      the SRL/CsA combination. An amendment was introduced in the protocol to
      drastically reduce the CsA exposure to <50 ng/mL (trough) at the time of SRL
      addition. After this amendment, 39 other KTx patients entered the study and only
      3 of 39 (8%) were discontinued because of toxic side effects. In the overall
      cohort of 81 KTx patients, the incidence of AR after SW was low (n = 5, 6.1%),
      all occurring within the first 3 months after SW. These findings indicate: (1)
      addition of SRL to very low-maintenance CyA exposure allows safe SW in KTx; (2)
      with the SRL + CsA combination, the incidence of AR after SW is low in long-term
      KTx patients; and (3) in the first 3 months after SW strict monitoring for early
      diagnosis and treatment of AR is mandatory.

PMID- 15848546
TI  - The effect of rapamycin on the healing of the ureteric anastomosis and wound
      healing.
AB  - Rapamycin is a potent immunosuppressive agent that also inhibits fibroblastic
      activity and therefore may affect the healing of various tissues. The aim of this
      study was to investigate the effect of rapamycin on wound healing and the healing
      of the ureteric anastomosis. Large White/Landrace pigs were subjected to a
      laparotomy and division and immediate anastomosis of the ureter. The animals were
      randomly allocated to receive either rapamycin or placebo. The animals were
      sacrificed on postoperative day 5, and strips of the skin and fascia closure and
      the ureteric anastomosis excised and used to determine the tensile strength,
      hydroxyproline levels, and histological changes. The tensile strength and the
      hydroxyproline levels in the ureter and fascia were lower in the rapamycin
      treated animals. There was no difference in the tensile strength in the skin,
      although the hydroxyproline levels were lower. This study shows that healing of
      the ureteric anastomosis and fascia and skin closure may be impaired by
      rapamycin.

PMID- 15848547
TI  - Effect of rapamycin on the healing of the bile duct.
AB  - Besides its potent immunosuppressive properties, rapamycin also has antitumor and
      antifungal effects. Rapamycin also inhibits the proliferation of fibroblasts and
      therefore may impair the healing of various tissues. We investigated the effect
      of rapamycin on the healing of the bile duct anastomosis. The study was
      undertaken in pigs that were subjected to a laparotomy under general anesthesia.
      The bile duct was mobilized and divided and immediately reanastomosed. The
      animals were randomly allocated to receive either rapamycin or placebo. The
      animals were sacrificed on the postoperative day 5, then the biliary anastomosis
      was excised and used to determine the tensile strength, hydroxyproline levels,
      and the histological changes. The tensile strength and the hydroxyproline levels
      in the biliary anastomosis were lower in the animals treated with rapamycin. The
      liver function tests were normal. These studies show that rapamycin may impair
      the healing of the biliary anastomosis.

PMID- 15848548
TI  - Severe limb lymphedema in sirolimus-treated patients.
AB  - We report two kidney transplant recipients who developed severe limb lymphedema
      under sirolimus (SRL) immunosuppression. The patients received SRL 10 and 2 mg/d
      to achieve target levels of 10 to 20 ng/mL with tapering doses of prednisone.
      Renal function and drug levels were monitored monthly. Patient 1 developed
      lymphedema of the left upper limb 3 years posttransplantation, after having been
      exposed to high SRL doses in the preceding 2 years (mean SRL dose-9.5 mg/d, mean
      trough level-26.3 ng/mL, mean serum creatinine-1.63 mg/dL). In patient 2
      lymphedema of both upper and lower right limbs occurred 18 months
      posttransplantation (mean SRL dose-3.2 mg/d, mean trough level-8.8 ng/mL, mean
      serum creatinine-2.9 mg/dL). Hypercholesterolemia and hypertriglyceridemia were
      also observed in both patients before SRL reduction/conversion. No signs of
      hematopoietic toxicity were observed. In both patients magnetic resonance (MR)
      angiography of the limb was negative for vascular obstruction, and
      lymphoscintigraphy revealed lymphatic obstruction. In patient 1 lymphedema
      improved significantly following SRL reduction and lymphatic drainage massage
      therapy. Patient 2 was converted to cyclosporine (CsA) improving markedly after
      conversion. Hypercholesterolemia and hypertriglyceridemia also improved
      significantly in both patients after reduction/conversion. We conclude that SRL
      may facilitate the occurrence of lymphatic obstruction by mechanisms that are
      presently unexplained. Lymphedema of the limbs in renal transplant recipients
      under SRL treatment, especially if on the same side as the hemodialysis access,
      should warn the transplant physician to rapidly reduce or withdraw SRL before the
      occurrence of complete obstruction.

PMID- 15848549
TI  - Cyclosporine and rapamycin act in a synergistic and dose-dependent manner in a
      model of immunosuppressant-induced kidney damage.
AB  - The combination of cyclosporine (CSA) and rapamycin (RAPA) is a potent and
      commonly used approach to immunosuppression following solid-organ
      transplantation. By applying varying doses of CSA and RAPA to the rat salt
      depleted model, we aimed to find a dose combination that favored
      antiproliferation/antifibrosis rather than toxicity. Male Sprague-Dawley rats
      (350 to 500 g) were salt-depleted for 7 days prior to commencing CSA and RAPA
      treatment. Serum creatinine and urinary protein/creatinine ratios were measured.
      Fibrosis was estimated with Sirius red staining of extracellular collagen. mRNA
      expression of TGF-beta, MMP-2, MMP-9, TIMP-1, and collagen III was assessed with
      reverse transcriptase PCR. A rise in serum creatinine at 7 and 28 days was
      observed for CSA 15 mg/kg/d (P = .002) but not CSA 7.5 mg (P = .06) or RAPA 1 mg
      (P = .69) compared to controls. Twenty-four-hour urinary protein excretion was
      unchanged compared to controls for all drug doses and combinations. Of the dose
      combinations, CSA 7.5 mg/d + RAPA 0.5 mg/d produced the lowest serum creatinine
      for all time points, and inhibited profibrotic TIMP-1 (P = .017), while
      increasing antifibrotic MMP-2 (P = .009) mRNA expression, compared to CSA
      treatment alone. Expression of TGF-beta and collagen III was unaltered between
      groups. CSA treatment produced molecular and biochemical changes indicating renal
      damage. Addition of RAPA can attenuate this damage, but only with a dose
      reduction of both agents. The most favorable results were for the dose
      combination CSA 7.5 mg/kg/d plus RAPA 0.5 mg/kg/d.

PMID- 15848550
TI  - Sirolimus delays recovery from posttransplant renal failure in kidney graft
      recipients.
AB  - The aim of this study was to evaluate the impact of sirolimus and cyclosporine
      (CsA) combined therapy on the incidence and duration of delayed graft function
      (DGF), and the impact of the latter on 1-year graft function. The study entailed
      23 cadaveric renal recipients treated with sirolimus-CsA-prednisone regimen
      (sirolimus group). The reference group entailed 23 patients treated with CsA
      azathioprine-prednisone. In the sirolimus group the frequency of DGF was 39% and
      was essentially the same as in reference group (34.8%). The duration of DGF was
      significantly longer in SRL group and lasted 21.2 +/- 12.2 days versus 6.8 +/-
      2.5 in reference group (P = .004). Serum creatinine level decreased below 3.0
      mg/dL after 36 +/- 22 days in sirolimus group versus 16.8 +/- 6 days in reference
      group (P < .04). Cold ischemia was slightly longer and donors were older in DGF
      patients in both groups. Sirolimus dose during first month was higher in DGF
      patients (3.5 versus 2.6 mg), whereas level of CsA was lower (230 versus 310
      ng/mL). Biopsy-proven acute rejection (AR) occurred in most of DGF patients and
      during the DGF period. Serum creatinine level at the 12th month posttransplant
      was higher in DGF versus non-DGF patients (2.0 +/- 0.5 versus 1.5 +/- 0.4 mg/dL).
      One-year patient and graft survival was 100% in sirolimus group and 100% and 95%
      in reference group. In conclusion, sirolimus significantly retards the recovery
      from posttransplant renal failure; however, it does not increase the incidence of
      DGF. Patients who suffered from posttransplant acute renal failure had worse
      renal function at 1 year after transplantation, independent of the treatment
      protocol.

PMID- 15848551
TI  - Mizoribine in combination therapy with tacrolimus for living donor renal
      transplantation: analysis of a nationwide study in Japan.

PMID- 15848552
TI  - Gastrointestinal-specific patient-reported outcome instruments differentiate
      between renal transplant patients with or without GI complications.
AB  - BACKGROUND: Gastrointestinal (GI) complications are frequently reported postrenal
      transplant and are often associated with immunosuppressant regimens including
      mycophenolate mofetil (MMF). This study evaluated the ability of two GI-specific
      patient-reported outcome (PRO) instruments to differentiate between patients with
      and without GI complaints. METHODS: Discriminant validity of the Gastrointestinal
      Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI),
      as well as two generic instruments (Psychological General Well-Being Index (PGWB)
      and EQ-5D, was assessed in a multinational study of renal transplant recipients.
      Patients received therapy that included a calcineurin inhibitor and MMF. Both t
      tests and ANOVAs were used to examine differences between patients with and
      without GI complaints, among levels of severity, and between patients reporting
      presence/absence of specific GI side effects. RESULTS: Of 96 patients recruited
      (56% male), 43% had none, 39% mild, 13% moderate, and 6% severe GI symptoms. All
      GSRS subscales and the GIQLI total and four of the five subscale scores
      significantly differentiated between patients with/without GI complications (P <
      .05). The PGWB total score and three subscales, the EQ-5D significantly
      differentiated between the two groups (P < .05). Only GI-specific instruments
      discriminated between some severity levels; for example, the GSRS abdominal pain
      subscale discriminated between patients at all levels of severity (P < .05). The
      GIQLI total score and symptoms subscale differentiated between patients with no
      symptoms and those with mild or moderate or severe symptoms (P < .05).
      CONCLUSIONS: The GSRS and GIQLI differentiated between patients with/without GI
      side effects and by symptom severity better than did generic instruments,
      demonstrating excellent discriminant ability in this population.

PMID- 15848553
TI  - Does mycophenolate mofetil increase the incidence of cytomegalovirus disease
      compared with azathioprine after cadaveric kidney transplantation?
AB  - Although most of the published papers had not found increase in the incidence of
      CMV disease in kidney transplant recipients treated with mycophenolate mofetil
      (MMF), we had feeling from everyday practice that after its introduction number
      of patients with CMV disease has increased. To test this hypothesis, we performed
      retrospective analysis of our database, comparing the incidence of CMV disease in
      patients treated with azathioprine (AZA) and patients treated with MMF. CMV
      disease was defined as CMV antigenemia (positive CMV pp65 determined by ELISA
      test) plus any of the following: decrease leucocytes or platelets, increased
      transaminases, increase in serum creatinine. The azathioprine treated group (AZA
      group) included 280 patients (132 female) treated for 17,672 months with AZA +
      Cyclosporine A (CyA) + steroid, or AZA + steroid, while the MMF group included
      219 patients (112 female) treated for 5079 months with MMF + CyA + steroid, or
      MMF + steroid. There was no difference in acute rejection episodes between the
      AZA and the MMF group. The AZA group had 51 CMV disease episodes (1 episode per
      346.5 treatment months), and the MMF group experienced 43 episodes (1 per 118.1
      months) (P < .01). Mean onset of CMV disease was 32.65 +/- 47.69 (SD) months
      after transplantation in the AZA group, and 3.72 +/- 4.43 in the MMF group. There
      was no difference between two treatment groups regarding the donor-recipient CMV
      status mismatch. Despite having the increased incidence of CMV disease, MMF group
      had less severe disease compared to AZA group with decrease in leukocyte count in
      11.6% vs 15.7% of episodes, decrease in platelet count in 20.9% vs 21.6%,
      elevation of transaminases in 18.6% vs 29.4% respectively, and finally increase
      in serum creatinine greater than 20% in 51.2% in MMF vs 74.5% in AZA group. Five
      patients from the AZA group experienced CMV pneumonitis with the mortality rate
      of 80%. Only one patient from the MMF group had CMV pneumonitis, and he survived.
      According to our results, patients treated with MMF have increased risk for
      development of CMV disease. However, the disease course is less severe, and less
      frequently accompanied with deterioration of renal function in comparison to the
      AZA group.

PMID- 15848554
TI  - Mycophenolic acid metabolite profile in renal transplant patients receiving
      enteric-coated mycophenolate sodium or mycophenolate mofetil.
AB  - Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is an
      effective immunosuppressive treatment in renal transplant recipients but is known
      to have gastrointestinal side effects. Enteric-coated mycophenolate sodium (EC
      MPS; myfortic) is a new formulation for delivering MPA. This open-label, two
      period, cross-over study was carried out to characterize the time course of MPA
      and its metabolites, mycophenolic acid glucuronide (MPAG) and acyl mycophenolic
      acid glucuronide (AcMPAG) in stable renal transplant patients (n = 40) after 28
      day chronic dosing with EC-MPS (720 mg bid) or MMF (1000 mg bid). The relative
      abundance and exposure of all three compounds was also assessed. EC-MPS
      demonstrated the typical pharmacokinetic profile of an enteric-coated formulation
      with a delayed release of MPA compared with MMF (Tmax 2.5 versus 1.0 hours,
      respectively). Consistent with a similar disposition of MPA, both EC-MPS and MMF
      treatments resulted in the same ratio of MPAG to MPA exposure, 23:1. Furthermore,
      comparison of the AUC of MPAG and AcMPAG for both treatments indicated that
      steady state MPAG exposure was 75 to 90 times that of AcMPAG, confirming MPAG as
      the predominant metabolite of MPA. AcMPAG has been identified as a possible
      active metabolite of MPA; the present study indicates that AcMPAG may contribute
      around 14% of the exposure to active drug after administration of MPA. Both EC
      MPS and MMF treatments were well tolerated over the 1-month period of chronic
      treatment. In summary, consistent with its enteric-coated design, EC-MPS delays
      delivery of MPA, but results in similar exposure to that provided by MMF.

PMID- 15848555
TI  - Mycophenolate mofetil pharmacokinetic monitoring in pediatric kidney transplant
      recipients.
AB  - This open-label, longitudinal, long-term study of de novo pediatric renal
      transplant recipients was designed to investigate the pharmacokinetics (PK) of
      mycophenolic acid (MPA) and its possible interaction with cyclosporine (CsA).
      Thirty-four children on an immunosuppressive regimen of CsA, prednisone, and
      mycophenolate mofetil (MMF, 300-400 mg/m2 twice daily) were investigated at 6,
      30, 180, and 360 days after transplantation. Considerable interindividual
      variability in the areas under the concentration curve (AUC(0-12)) of MPA was
      observed during the follow-up, although the dose of MMF remained the same over
      the same time. Predose levels (C0) increased significantly during the first 6
      months after transplantation: C0 at 6 and 180 days after transplantation was 0.8
      +/- 0.6 and 1.9 +/- 1.1 microg/mL (P < .0001). A significant time-dependent
      increase in the AUC of MPA was also observed during the first 6 posttransplant
      months: AUC(0-12) at 6 and 180 days after transplantation was 23.3 +/- 10.8 and
      40 +/- 11.6 mg*h/L (P = .003). MPA concentrations 3 and 4 hours after MMF intake
      were the individual time points that best correlated with the full MPA AUC (r =
      0.8 and 0.79; P < .001). The abbreviated MPA AUC (0-4 hours) correlated
      reasonably with the full AUC (r = 0.87; P < .001). Finally, a significant
      reduction in CsA dose during the first 6 posttransplant months (P < .001) matched
      the significant increases in both MPA C0 and full MPA AUC, thus demonstrating the
      interaction of the 2 immunosuppressive drugs. These observations suggest the need
      for therapeutic drug monitoring when adjusting the dose of MMF in children.

PMID- 15848556
TI  - Therapeutic drug monitoring of mycophenolic acid in renal transplant recipients.
AB  - Immunosuppressive regimens including mycophenolate mofetil (MMF, Cellcept) were
      used in a renal transplant transplant program since May 2000 including 67
      patients in whom it was the primary drug. Acute rejection (AR) occurred in 9
      cases (13%) with 1-year graft survival rate of 96.8%. Pharmacokinetic (PK)
      studies of mycophenolic acid (MPA) were performed in 46 recent patients (total,
      127 times). There was no correlation between dose (mg/kg) and blood concentration
      (AUC0-9: r2= 0.27). AUC0-9 was well correlated with AUC0-4 (r2= 0.91), but not
      with a single timepoint concentration. MPA AUC0-9 level was significantly higher
      among the AR-negative group (n = 33; 34.2 +/- 16.8 ng.hr/mL) compared with AR
      positive group (n = 3; 28.2 +/- 1.9 ng.hr/mL; P = .04085) over the 2 weeks after
      transplantation. MPA AUC0-9 level was higher among the adverse event (AE
      positive) group (n = 15; 39.2 +/- 22.8 ng.hr/mL) compared with the negative group
      (n = 21; 30.1 +/- 8.0 ng.hr/mL; P = .08772) within 2 weeks after transplantation.
      These results suggest the necessity of measuring AUC for therapeutic drug
      monitoring (TDM) of MMF-containing immunosuppressive therapy. The possible target
      level of MPA AUC0-9 would be approximately 30 ng.hr/mL using the present
      immunosuppressive regimen.

PMID- 15848557
TI  - Standard dose enteric-coated mycophenolate sodium (myfortic) delivers rapid
      therapeutic mycophenolic acid exposure in kidney transplant recipients.
AB  - Previous studies have shown poor absorption of enteric-coated mycophenolate
      sodium (E-MPS) during the initial post-kidney transplantation (KT) period. The
      percentage of patients with adequate therapeutic exposure (target AUC 30-60
      microg.h/mL) of mycophenolic acid is 55%, 86%, and 100% at days 14, 90, and 180
      postgrafting. To assess the adequacy of mycophenolic acid (MPA) delivery during
      the initial period, we prospectively studied the pharmacokinetics (AUC0-12 h of
      MPA (measured by high-performance liquid chromatography) in 12 patients after
      their first single dose of 720 mg of oral E-MPS and 3 to 8 months after 720 mg
      twice a day prescribed daily. Concomitant immunosuppression included CsA and
      prednisolone. Evaluation of the pharmacokinetic profiles was repeated at 2 weeks.
      The patients' mean +/- SD body weight was 48.1 +/- 8.8 kg; their mean (range)
      values of AUC0-12 h for MPA were 73.9 +/- 49.5 microg.h/ml (31.9-190) on day 1
      and 74.3 +/- 44.3 (30.5-178) microg.h/ml on day 14. The mean nadir serum
      creatinine was 1.1 +/- 0.4 mg/dL. The patient and graft survival rates were 100%.
      Two patients (15%) developed significant diarrhea requiring E-MPS dose reduction.
      Other complications included urinary tract infections (n = 2), CMV syndrome (n =
      1), borderline acute rejection (n = 1), and reversible CsA nephrotoxicity (n =
      3). We conclude that the use of a standard dose of E-MPS results in immediate
      delivery of adequate therapeutic systemic MPA exposure in all patients. The
      absorption profile was better than that described previously.

PMID- 15848558
TI  - Pharmacokinetics of mycophenolic acid in kidney transplant patients receiving
      sirolimus versus cyclosporine.
AB  - INTRODUCTION: Mycophenolic acid (MPA) pharmacokinetics exhibit large variability
      in transplant recipients and may be altered due to concurrent immunosuppressants.
      Little is known about the influence of sirolimus (SRL) on MPA pharmacokinetics in
      kidney transplant patients. METHODS: We studied the areas under concentration
      time curves (AUC) for MPA in 15 patients receiving immunosuppression combining
      SRL with mycophenolate mofetil (MMF). The pharmacokinetic measurements were
      performed in all patients using three MMF dosing regimens (0.5 g twice a day,
      0.75 g twice a day, 1 g twice a day). Similar blood AUC profiles were also
      sampled from 12 patients treated with a fixed dose of MMF 1 g twice a day and
      cyclosporine (CsA). MPA was measured using HPLC; the AUC0-12 of MPA was
      determined by the trapezoidal method using four sampling time points: C0, C1, C3,
      C5. RESULTS: While patients on SRL were receiving 0.75 g MMF twice a day, mean
      AUC0-12 and C0 values of MPA were comparable to those of patients receiving CsA
      and 1 g MMF twice a day (54.1 +/- 17.6 and 3 +/- 1.87 vs 51.7 +/- 16.7 mg.h/L and
      2.76 +/- 1.57 mg/L, respectively). On the other hand, 0.5 g MMF twice a day with
      SRL therapy resulted in AUC0-12 and C0 values of MPA of 32.3 +/- 12.6 mg.h/L and
      2.32 +/- 1.72 mg/L, respectively, whereas, 1 g MMF twice a day with SRL resulted
      in AUC0-12 and C0 values of MPA of 70.9 +/- 19.3 mg.h/L and 4.7 +/- 2.44 mg/L,
      respectively. CONCLUSIONS: These findings demonstrate that MPA exposure in the
      presence of SRL is higher than that with CsA. It appears that the MMF dose should
      be reduced to 0.75 g twice a day in patients receiving SRL to obtain AUC0-12 of
      MPA levels comparable to that in patients treated with CsA and MMF 1 g twice a
      day.

PMID- 15848559
TI  - Conversion of stable kidney transplant recipients from a twice daily Prograf
      based regimen to a once daily modified release tacrolimus-based regimen.
AB  - Modified release (MR) tacrolimus is an extended release formulation administered
      once daily (qD). The purpose of this pharmacokinetic (PK) study was to evaluate
      tacrolimus exposure in stable kidney transplant recipients converted from Prograf
      twice a day to MR tacrolimus qD. METHODS: This was an open-label, multicenter
      study with a crossover design. Eligible patients were 18 to 65 years of age, more
      than 6 months posttransplant with stable renal function, and received stable
      Prograf doses more than 2 weeks prior to enrollment. Patients received Prograf
      twice a day through day 7; 24-hour PK profiles were obtained on days 1 and 7.
      Patients were converted to the same milligram-for-milligram daily dose of MR
      tacrolimus qD in the morning on day 8; 24-hour PK profiles were obtained for MR
      tacrolimus on days 8, 14, and 21. Laboratory and safety parameters were also
      evaluated. RESULTS: Most patients (67 of 70) completed all 5 PK profiles. The 90%
      confidence intervals (CI) for the MR tacrolimus vs Prograf comparison at steady
      state (days 14 and 21 vs days 1 and 7) were 90.7 and 99.4 for AUC0-24 and 82.7
      and 91.9 for Cmin. MR tacrolimus was well tolerated with a safety profile
      comparable to that of Prograf. AUC0-24 was highly correlated to Cmin for Prograf
      (day 1, r = 0.80; day 7, r = 0.84) and MR tacrolimus (day 14, r = 0.92; day 21, r
      = 0.86). Renal function remained stable after conversion to MR tacrolimus.
      CONCLUSION: The steady state PK of MR tacrolimus are equivalent to Prograf after
      a milligram-for-milligram conversion in stable kidney transplant recipients. The
      results provide evidence to support a safe 1:1 conversion from Prograf twice a
      day to MR tacrolimus.

PMID- 15848560
TI  - Two-hour post-dose cyclosporine levels in renal transplantation in Argentina: a
      cost-effective strategy for reducing acute rejection.
AB  - Monitoring of cyclosporine (microemulsion CsA) at 2 hours post-dose (C2), a
      measure of absorption and exposure, appears superior to trough (C0) monitoring
      for prediction of rejection risk. The purpose of this study was to determine
      whether C2 was cost-effective compared to C0 in Argentina. METHODS: A predictive
      decision model was adapted to Argentina to predict costs associated with C0 and
      C2 measurements in the first year after transplantation. Patients were treated
      with microemulsion CsA, steroids and azathioprine or MMF. Parameter estimates for
      the C0 strategy were based on event rates observed in published clinical trials.
      The model was adapted to Argentinean health system through local protocols and
      expert opinions; costs were valued in Argentinean pesos and converted to US
      dollars (1 USD = 2.85 ARS). RESULTS: Incidence of acute rejection was predicted
      to be 25.0% at 1-year among patients monitored by C0 and 18.0% by C2. Graft
      survival was predicted to be 1.4% lower in the C0 group. No important differences
      were identified in co-morbidity, C0 and C2 monitoring costs, and in ambulatory
      based adverse events between C0 and C2 cohorts. The model predicted an average
      cost per patient of $16,269 for C0 and $16,343 for C2 testing (year 1).
      Sensitivity analyses indicated that the average daily dose of microemulsion CsA
      was the most important parameter leading to the incremental cost per patient.
      CONCLUSIONS: C2 is expected to provide a potentially important reduction in the
      risk of acute rejection without increasing the estimated cost of care in the
      first year post-transplant.

PMID- 15848561
TI  - Sequential blood level monitoring of basiliximab during multisession
      plasmapheresis in a kidney transplant recipient.
AB  - Basiliximab, a chimeric monoclonal antibody against the alpha chain of the
      interleukin-2 receptor (IL-2R) has been used in renal transplant patients. We
      monitored sequential blood concentrations of basiliximab in a patient who
      received a kidney transplant with basiliximab-based immunosuppression together
      with multiple sessions of plasmapheresis. A 34-year-old man received a living
      related kidney transplant with induction immunosuppression including tacrolimus,
      mycophenolate, methylprednisolone, and basiliximab. Severe antibody-mediated
      acute rejection lead to a requirement for hemodialysis. Deoxyspergualin was
      administered for 10 days at a daily dose of 5 mg/kg combined with eight sessions
      of double filtration plasmapheresis (DFPP). After treatment, the serum creatinine
      returned to 0.95 mg/dL, and there were no major complications or infections.
      Sequential basiliximab blood levels of the patient were monitored following
      transplantation. The serum basiliximab concentration decreased by 72.4% after
      five consecutive DFPPs, and by 87.6% after eight DFPP sessions. The elimination
      rate of basiliximab (DeltaBLX) was 6.1% before DFPP, but increased over eight
      DFPPs to 20.5%. Serum basiliximab concentrations declined to 0.16 microg/mL on
      day 33, which is below the IL-2R saturation concentration (0.2 microg/mL).
      Multiple sessions of plasmapheresis using DFPP enhanced the elimination of serum
      basiliximab at an average elimination rate of 19.1%. In the patient reported on
      here, the serum basiliximab concentration fell to below the IL-2R saturation
      level (0.2 microg/mL) within 1 month of living-related kidney transplantation. We
      recommend that additional basiliximab infusions be considered for cases
      undergoing more than three plasmapheresis sessions.

PMID- 15848562
TI  - The effect of urinary protein excretion in post-renal transplant recurrent
      nephrotic syndrome on basiliximab pharmacokinetics and pharmacodynamics in a
      pediatric patient.
AB  - A pharmacokinetic and pharmacodynamic study of Basiliximab therapy has not been
      reported in recurrent post-renal transplant nephrotic syndrome. We assessed the
      effect of urinary protein in a focal segmental glomerulosclerosis patient. We
      measured the serum concentrations of basiliximab as well as the rate of activated
      CD25-positive T lymphocytes at fixed intervals in nephrotic versus eight
      nonnephrotic pediatric post-renal transplant patients. A significant reduction in
      the antibody concentrations was observed in focal segmental glomerulosclerosis.
      The CD25 expression rate showed a similar trend to the pharmacokinetic data. We
      conclude that cases of massive urinary protein excretion need special care to
      maintain immunosuppression in renal transplant using Basiliximab.

PMID- 15848563
TI  - Excellent results with calcineurin inhibitor-free initial immunosuppression in
      old recipients of old kidneys.
AB  - The ever increasing demand for donor organs has forced transplant surgeons to
      liberalize selection criteria. To avoid initial nephrotoxicity to kidneys from
      donors over 65 years of age, immunosuppression was begun with an IL-2 receptor
      antibody, mycophenolate mofetil, and steroids in a total of 38 recipients over 65
      years. Calcineurin inhibitors (CI) were added after sufficient graft function was
      reached. After a mean cold ischemia time of 14:01 hours and a delayed function
      rate of 31%, patient survival, graft survival, and serum creatinine were 97.4%,
      94.7%, and 1.5 mg/dL at 1 and 92.1%, 92.1%, and 1.7 mg/dL at 2 years,
      respectively. Thus, excellent results can be achieved in old recipients of old
      donor kidneys with CI-free initial immunosuppression.

PMID- 15848564
TI  - The safety and efficacy of early withdrawal of calcineurin inhibitors in kidney
      transplant recipients 6 months' posttransplant.
AB  - INTRODUCTION: The introduction of calcineurin inhibitors (CNIs) in clinical
      transplantation has resulted in dramatic reduction in acute rejection rate and
      improvements in short-term allograft survival. However, CNI-induced chronic
      nephrotoxicity is a clinical concern since it is a major cause of chronic
      allograft failure. Recent studies suggest that withdrawal or reduction of CNI
      dosage results in improvement in graft function and survival. The aim of this
      study was to evaluate the safety and efficacy of substituting CNIs with
      mycophenolate mofetil (MMF) at 6 months' postkidney transplant. METHODS: Kidney
      transplant recipients of first or second grafts (n = 20) maintained on CNI-based
      therapy and with no history of irreversible acute or vascular rejection were
      included in the study. Primary end points were the incidence of biopsy-proven
      acute rejection or treatment failure. Secondary end points included changes in
      mean serum creatinine and estimated GFR (Cockroft and Gault, CG) over time,
      incidence of infection, cardiovascular risk factors (blood pressure,
      cholesterol), graft and patient survival rates, as well as incidence of biopsy
      proven chronic allograft nephropathy (CAN). Study patients were compared to a
      matched control group (n = 20) who remained on CNI-based therapy at equivalent
      time points. RESULTS: Incidence of acute rejection following CNI withdrawal was
      15%. All episodes reversed with steroid pulses. There was no significant
      difference in mean serum creatinine or estimated GFR during the follow-up period.
      No significant change occurred in blood pressure or antihypertensive agents
      between the groups; however, there was a trend toward lower cholesterol levels
      after CNI withdrawal. No graft or patient loss was seen during the study period.
      Biopsy-proven CAN was diagnosed in 2 control patients (10%) at 6 to 8 months'
      posttransplant. CONCLUSIONS: Withdrawal of CNI at 6 months following kidney
      transplantation is associated with an increased risk of rejection and a trend
      toward lower serum creatinine and cholesterol levels. Further follow-up is needed
      to establish the long-term results of CNI-sparing regimens on the development of
      CAN.

PMID- 15848565
TI  - Multivariate analysis of the effectiveness of using antibody induction therapy
      according to the degree of HLA mismatches.
AB  - OBJECTIVE: HLA mismatches have a strong impact on acute rejection and renal
      allograft survival. The objective of this study was to evaluate the effectiveness
      of antibody induction according to the degree of HLA mismatches. METHODS: Of
      20,429 deceased donor (DD) transplantations and 12,859 living donor (LD)
      transplantations reported to the United Network for Organ Sharing (UNOS) between
      1999 and 2001, 51% of DD and 45% of LD transplant recipients received induction
      therapy. Propensity scores (PS) were calculated to indicate independent factors
      associated with the use of induction. Levels of HLA match examined for DD
      transplant recipients were 0 ABDR (n = 3239), 0 DR (n = 4210), and DR mismatched
      transplants (n = 12,980), and 0 (n = 1133), 1 (n = 3836), and 2 (n = 7890)
      haplotype mismatches for LD transplant recipients. Outcome parameters were
      reported as hazard ratios (HR) for graft loss and odds ratios (OR) for first-year
      acute rejection. RESULTS: Recipients with HLA mismatches were more likely to
      receive induction antibody for DR mismatch in DDs (PS = 1.11, 95% confidence
      interval [CI] 1.04-1.19) and for haplotype mismatch in LDs (PS = 1.36, 95% CI
      1.22-1.52). Induction reduced the likelihood of acute rejection for DD transplant
      recipients regardless of the level of HLA mismatch (OR = 0.70; 95% CI 0.57-0.85
      in 0 ABDR MM; OR = 0.76, 95% CI 0.64-0.89 in 0 DR MM; and OR = 0.69, 95% CI 0.62
      0.77 in DR MM), and for 2 haplotype mismatched LD transplant recipients (OR =
      0.82, 95% CI 0.70-0.96); in other LD transplant recipients, reductions in acute
      rejection rates were observed but not statistically significant. Induction
      reduced the risk of graft loss for DR mismatched DD transplant recipients by
      about 12% (HR = 0.88; 95% CI 0.80-0.97). CONCLUSIONS: Antibody induction resulted
      in a significant reduction of acute rejection and graft loss for patients with
      HLA mismatch.

PMID- 15848566
TI  - Multivariate analysis of antibody induction therapy and their associated outcomes
      in deceased donor transplants.
AB  - AIMS: The aims of this study were to describe factors associated with the use of
      overall induction, classes of induction agents, and to evaluate the incidence of
      acute rejection, short-term graft survival, and patient survival. METHODS: Of
      24,901 transplants reported to the United Network for Organ Sharing (UNOS)
      between 1999 and 2001, 51% received induction therapy including Thymoglobulin (T;
      n = 3090), Simulect (S; n = 6063), or Zenapax (Z; n = 3755). Propensity scores
      (PS) were calculated to indicate factors associated with use of induction and for
      each induction agent. Outcome parameters included graft survival (GS), hazard
      ratio (HR) for graft loss (GL), and odds ratio (OR) for first-year acute
      rejection (AR). RESULTS: Pediatric (PS = 1.29; 95% confidence interval [CI] 1.12
      1.49, vs adults) and retransplanted recipients (PS = 1.36; 1.23-1.49, vs first)
      were more likely to receive induction. One-year GS (90.1 vs 88.0%; P < .001), GL
      = 0.92% (0.86-0.98; P = .01), and AR free = 0.74 (P < .001) were superior in
      patients receiving induction. Using multivariate analysis, the odds of rejection
      0.73 (0.68-0.78), GL 0.91 (0.85-0.97), and death 0.90 (0.82-0.98) were lower in
      those receiving induction. Among patients given induction, those receiving T were
      more likely sensitized (PS = 1.50%; 1.31-1.71), retransplanted (PS = 1.51; 1.31
      1.75), or had delayed graft function (PS = 1.75; 1.58-1.93). T decreased the odds
      of rejection compared with S or Z (OR = 0.74; 0.69-0.79), but the type of
      induction agent did not have an impact on graft outcome HR for T = 1.07 (0.96
      1.19). CONCLUSIONS: The use of antibody induction was associated with lower risk
      of rejection and better GS. There were no differences in GS among individual
      regimens. Comparative safety data were not analyzed but should be taken into
      consideration when choosing antibody preparations.

PMID- 15848567
TI  - Comparison of induction based on continuous vs discontinuous administration of
      antithymocyte globulins in renal transplant patients: efficacy and long-term
      safety.
AB  - This retrospective study sought to compare two modes of administration of
      antithymocyte globulin (RATG) after renal transplantation. METHODS: Before 1993,
      group I patients (n = 93) received fixed doses of RATG (1 mg/kg per day) for 8
      consecutive days. Thereafter, RATG was either continued at the same dose for 15
      days, in cases of delayed graft function, or was infused every other day at the
      same dose until serum creatinine level became <150 micromol/L. After 1993, group
      II patients (n = 66) received RATG at full dose (1 mg/kg per day) during the
      first 3 days and thereafter the doses were adjusted to target a CD2 T-cell count
      <50/mm3. Both groups received steroids, azathioprine, and cyclosporine. The mean
      follow-up after transplantation was 117 +/- 31 months in group I and 93 +/- 19
      months in group II. RESULTS: The RATG cumulative dose and consequently cost were
      significantly higher among group I than group II patients. Long-term patient and
      graft survival were similar in both groups. The rate of acute graft-rejection
      episodes was significantly higher among group I than group II patients. At 7
      years posttransplantation, the serum creatinine level and creatinine clearance
      were similar in the two groups. The rate of cytomegalovirus infection, as well as
      the cumulative incidence of severe infections and cancers were also similar in
      both groups. Among the cancers, skin neoplasms represented 30% in group I and 26%
      in group II (P = ns). CONCLUSION: Adjusting RATG doses according to the CD2
      lymphocyte count is safe, and a less expensive than using full doses.

PMID- 15848568
TI  - Cyclosporine-sparing effect of basiliximab in renal transplant recipients with
      mycophenolate mofetil.
AB  - Basiliximab added to a maintenance regimen consisting of cyclosporine
      microemulsion and mycophenolate mofetil was studied for its effectiveness in
      allowing early steroid withdrawal in renal transplantation. Furthermore, the
      cyclosporine-sparing effects between groups with and without basiliximab
      induction therapy were compared. PATIENTS: Between September 2001 and June 2003,
      90 patients underwent renal transplants with cyclosporine-based
      immunosuppression, namely, cyclosporine, mycophenolate mofetil, and
      methylprednisolone, (group 1; n = 25). During the latter half of the study
      basiliximab was administered during the induction phase (group 2; n = 65). In
      group 2, steroids were completely withdrawn on postoperative day 14 in 57
      patients. RESULTS: The incidence of acute rejection was significantly higher
      among group 1 patients (P = .005). The incidence of steroid-resistant rejection
      in group 1 patients was significantly higher (P = .025). At each time point
      cyclosporine levels in group 1 patients were significantly higher (P < .01). The
      incidence of infection was comparable between the groups. Patient and graft
      survival rates in group 1 were 100% and 100%; in group 2, they were 99% and 99%,
      respectively. In group 2, steroids were discontinued in 57 patients with
      permanent withdrawal achieved in 32 patients (56%). CONCLUSION: The use of
      basiliximab, together with mycophenolate mofetil allowed for a significant
      reduction in the cyclosporine dose without increasing the risk of acute
      rejection. Although further follow-up is necessary to confirm the effect, this
      regimen may attenuate cyclosporine nephrotoxicity thereby affecting the long-term
      outcomes of renal transplantation.

PMID- 15848569
TI  - Limited-dose Daclizumab versus Basiliximab: a comparison of cost and efficacy in
      preventing acute rejection.
AB  - The purpose of this study was to compare the efficacy and cost of the limited
      dose Daclizumab regimen to that of the standard-dose Basiliximab regimen. Two
      antibody induction regimens were compared in patients aged 18 years and older who
      received renal transplants from January 2002 to September 2003 and completed
      interleukin (IL)-2R antibody induction with standard-dose Basiliximab (20 mg x 2
      doses) or limited-dose Daclizumab (1 mg/kg x 2 doses). The primary outcome
      measure was the incidence of acute rejection. Secondary outcomes included cost,
      changes in serum creatinine level, and delayed graft function. Of the 46 patients
      randomized, 42 patients completed the 6-month follow-up. Mean serum creatinine
      level at time of discharge was originally higher in the limited-dose Daclizumab
      group than the standard-dose Basiliximab group (1.89 vs 1.57, respectively). By
      1, 3, and 6 months, mean serum creatinine values were similar between both
      groups, with a trend toward lower mean serum creatinine values in the limited
      dose Daclizumab group. The incidence of acute rejection was also similar between
      the groups (6% vs 7%). The average cost difference between the 2 regimens was
      approximately $715. This study suggests that a limited-dose Daclizumab regimen
      may be an efficacious and less costly alternative to the standard-dose
      Basiliximab regimen for antibody induction therapy following renal
      transplantation.

PMID- 15848570
TI  - Basiliximab (Simulect) reduces acute rejection among sensitized kidney allograft
      recipients.
AB  - AIMS: Our goal was to evaluate the efficacy and safety of basiliximab (Simulect)
      as immunosuppressive induction therapy for the prevention of acute allograft
      rejection among sensitized kidney recipients. METHODS: Fifty-six adult recipients
      receiving cadaveric kidney transplant with panel reactive antibody class I
      ranging from 30% to 50% and or class II 30% to 80% were randomized at about a 2:1
      ratio to the Simulect group (36 patients) or matching control group (20
      patients). All patients received baseline triple immunosuppressive therapy with
      cyclosporine (Neoral), mycophenolate mofetil, and steroids. Simulect was given in
      two doses of 20 mg each on day 0 (2 hours before operation) and day 4 after
      transplantation. RESULTS: There was no hyperacute rejection in either group and
      delayed graft function occurred in three control patients. The incidence of acute
      rejection during the first 3 months was 11.1% in the Simulect group compared with
      50% in the placebo group (77.8% reduction, P < .01). No apparent adverse and
      toxic events were recorded in the Simulect group. The mean daily dose of steroids
      was significantly higher in the control group 2 to 4 weeks posttransplantation.
      No clinically meaningful differences in the mean dose of cyclosporine were
      observed between the two groups; in addition, there were no statistically
      significant differences in the rate of patient or graft survival. CONCLUSIONS: On
      the basis of appropriate selection of the donor and recipient, Simulect is
      effective and safety for the sensitized recipients as immunosuppressive induction
      therapy.

PMID- 15848571
TI  - No-load sirolimus with tacrolimus and steroids is safe and effective in renal
      transplantation.
AB  - AIM: Basiliximab (BX) induction, tacrolimus (TAC), and steroids have sharply
      reduced acute cellular rejection at our institution. However, late graft loss has
      continued, for which sirolimus (SL) was introduced into the protocol. METHODS:
      From July 1, 2001 to December 31, 2003, 152 live donor (LD) renal transplant
      recipients received TAC (level 15 to 20 ng/mL) and steroids, with BX induction.
      One hundred twenty-two patients (Group 1) received SL (3 mg/d African-americans;
      2 mg/d for others) starting on days 2 and 3. The SL level was adjusted to 8 to 10
      ng/d, usually by weeks 3 to 4 posttransplant. The TAC doses were then
      progressively reduced. Records were reviewed for demographics, immunosuppressive
      drug levels, serum cholesterol and blood pressure, and complications. Graft and
      patient survival rates were calculated. Comparison was made to 53 LD recipients
      transplanted from July 1, 1998, to June 30, 2001 (Group 2) receiving BX, steroids
      and TAC, without SL. Recipients of deceased donor kidneys were excluded because
      of variability in kidney quality, ischemic time, and patient management. RESULTS:
      Demographics were similar between groups: African Americans, 25% to 35%; mean age
      36 years; mean HLA mismatch 3.7. Wound problems and infection were minimal in
      both groups. Mean serum creatinine and cholesterol and systolic and diastolic
      blood pressure measured periodically up to 1 year were similar, as was the
      incidence of rejection. In 25% of patients, SL was discontinued. CONCLUSIONS:
      Gradual introduction of SL appears to be associated with minimal wound problems.
      With more aggressive reduction in TAC, better renal function, and better long
      term graft survival may be attainable. We currently lower TAC levels to 5 ng/mL
      by 3 months.

PMID- 15848572
TI  - Long-term administration of enteric-coated mycophenolate sodium in kidney
      transplant patients.
AB  - A large-scale, controlled clinical study has shown that enteric-coated
      mycophenolate sodium (EC-MPS) is therapeutically equivalent to mycophenolate
      mofetil (MMF) in de novo renal transplant patients. Safety and efficacy outcomes
      from an open-label extension of this core study (n = 122) were compared to those
      of the MMF arm of two well-controlled randomized studies (RAD B251, n = 141, and
      RAD B201, n = 150) for the 12- to 36-month posttransplant period. During this
      period, 33 (27%) EC-MPS patients experienced one or more drug-related adverse
      event. Sixteen patients (13%) discontinued the extension study due to adverse
      events. The incidence of all safety parameters was similar in the EC-MPS patients
      and the MMF-treated patients in the RAD B201 and RAD B251 studies during the 12-
      to 36-month posttransplant period, as was the frequency of adverse events,
      infections, malignancies, and hematological abnormalities. During the 24 months
      of the EC-MPS extension study, four patients died and two lost their graft.
      Biopsy-proven acute rejection (BPAR) occurred in four patients (3.3%). BPAR,
      graft loss, and death occurred in a similar proportion of MMF-treated patients in
      the RAD B201 and RAD B251 studies during months 12 to 36 posttransplant. These
      findings confirm the safety and efficacy of EC-MPS in maintenance transplant
      patients at least 1 year posttransplant and suggest that outcomes with EC-MPS are
      comparable to MMF in this population when used in combination with CsA-ME and
      steroids.

PMID- 15848573
TI  - Safety and efficacy after conversion from mycophenolate mofetil to enteric-coated
      mycophenolate sodium: results of a 1-year extension study.
AB  - Enteric-coated mycophenolate sodium (EC-MPS) is an enteric-coated formulation of
      mycophenolic acid. A 12-month, multicenter, double-blind, randomized clinical
      study demonstrated that converting maintenance renal transplant patients from
      mycophenolate mofetil (MMF) to EC-MPS is safe and does not affect efficacy. In an
      open-label study extension, 130 patients initially randomized to MMF were
      converted to EC-MPS (newly exposed); 130 initially randomized to EC-MPS continued
      on EC-MPS (EC-MPS long-term). A composite endpoint of biopsy-proven acute
      rejection (BPAR), graft loss, or death occurred in 3 (2.3%) newly exposed and 2
      (1.5%) EC-MPS long-term patients during the extension phase. One patient died and
      one lost his graft. BPAR occurred in 3 (2.3%) newly exposed patients and 1 (0.8%)
      EC-MPS long-term patient. During the first 12 months of the extension phase,
      incidence and type of adverse events was similar in both groups and comparable to
      that seen in the core study. Nine cases of malignancy were reported, mainly
      nonmelanoma skin cancers. EC-MPS dose adjustments for adverse events were
      required in <12% of patients. At the end of the 12-month extension, 58 (44.6%)
      and 64 (49.2%) newly exposed and EC-MPS long-term patients, respectively, had
      reported at least one gastrointestinal adverse event. Mean serum creatinine
      remained stable at the 12-month visit of the extension study (137 micromol/L in
      the newly exposed and 142 micromol/L in the EC-MPS long-term groups). The results
      of this study demonstrate the long-term safety of EC-MPS and reconfirm the safety
      of converting MMF maintenance renal transplant patients to EC-MPS.

PMID- 15848574
TI  - Safety assessment of the conversion from mycophenolate mofetil to enteric-coated
      mycophenolate sodium in stable renal transplant recipients.
AB  - The immunosuppressant mycophenolate mofetil (MMF; CellCept) has greatly improved
      transplant recipients' clinical outcomes, but its efficacy may be limited by dose
      adjustments due to adverse events (AEs). An enteric-coated formulation of
      mycophenolate sodium (EC-MPS; myfortic), designed to improve gastrointestinal
      tolerability is now available. This Latin-American, prospective, multicenter,
      open-label, 6-month trial assessed the safety and tolerability of converting
      renal transplant recipients from MMF to EC-MPS. In total, 237 renal transplant
      recipients (stable > or = 3 months' posttransplant) receiving MMF (< or =1000 mg
      b.i.d.) were enrolled. Adults (n = 218) were converted to EC-MPS 720 mg b.i.d.
      (equimolar to MMF 1000 mg b.i.d.) even if they were initially receiving <1000 mg
      MMF b.i.d. (ie, 47 adults received a higher than equimolar dose of EC-MPS).
      Children (n = 19) were converted to EC-MPS 450 or 432 mg/m2 b.i.d. Patients also
      received cyclosporine microemulsion (Neoral) and corticosteroids. There were
      three acute rejections and no graft failures. The incidence of AEs was 59.9% (in
      those receiving a higher than equimolar EC-MPS dose it was 57.4%). In all, 22% of
      patients had gastrointestinal AEs, 37% had infections, and 4.8% had hematological
      AEs. Only 24 patients (10%) had an AE-related dose reduction. Seven of these
      patients had received higher than equimolar doses of EC-MPS. Patients can be
      safely converted from different doses of MMF to a standard dose of EC-MPS. The
      requirement for EC-MPS dose reduction to manage AEs was relatively low. Use of EC
      MPS is a valid alternative for renal transplant recipients receiving maintenance
      MMF treatment.

PMID- 15848575
TI  - Assessment of two strategies of neoral administration, early versus delayed, on
      renal function and efficacy in de novo renal transplant patients receiving
      myfortic, steroids, and anti-IL2R antibodies: 12-month results of a randomized,
      multicentre, open, prospective controlled study.
AB  - The optimal immunosuppressive strategy and benefit of delaying Neoral to prevent
      delayed graft function (DGF) have not been clearly established. Renal function
      was assessed by estimated creatinine clearance (Cockcroft-Gault) at 3 months, and
      efficacy by treatment failure and BPAR at 6 and 12 months after renal
      transplantation. Two hundred three patients were enrolled after stratification
      according to DGF risk (USRDS criteria). One hundred ninety-seven were randomized
      to receive either early (E; day 0; n = 97) or delayed (D; day 6; n = 100) Neoral
      in combination with myfortic, steroids, and anti-IL2R antibodies. Neoral was
      adjusted using C2. Six patients who were not randomized have been excluded from
      the intention-to-treat (ITT) analysis. RESULTS: There was no significant
      difference in the demographic or baseline parameters between the two groups. The
      risk of DGF(score > or = 5) was similar in both groups: 32 of 97 in E-Neoral
      versus 33 of 100 in D-Neoral. In the group at high risk for DGF, the incidence of
      DGF was 13 of 32 pts in E-Neoral versus 14 of 33 in D-Neoral. Renal function was
      not statistically different between the two groups in both the ITT and per
      protocol (PP) populations at 3, 6, or 12 months. Over 12 months, the evidence of
      treatment failure and BPAR were not statistically different: 24 of 97 (24.7%)
      versus 27 of 100 (27%) and 18 of 97 (18.6%) versus 24 of 100 (24%) for E-Neoral
      and D-Neoral, respectively. The severity of acute rejection was mild in 83%
      patients. CONCLUSION: These data suggest that there is no significant impact on
      renal function and immunosuppressing efficacy of early versus delayed
      introduction of Neoral, in combination with myfortic and steroids among renal
      transplant patients with or without a risk of DGF.

PMID- 15848576
TI  - Reversal of acute cellular rejection after renal transplantation with Campath-1H.
AB  - Between September 2002 and February 2004, 40 kidney transplant (27 from deceased
      and 13 from living donors) recipients (25 male and 15 female, aged 50.3 +/- 15.1
      years) were treated with Campath 1H (C 1H; 30 mg/dose IV) for biopsy-proven
      steroid-resistant rejection (SRR) or rejections equal to or worse than Banff 1B.
      All transplantations occurred between August 2001 and May 2003. All patients had
      received antibody preconditioning (RATG 5 mg/kg, n = 34; C 1H 60 mg, n = 4; C 1H
      30 mg, n = 2) preoperatively and were treated with Tacrolimus monotherapy (target
      level 10 ng/ml) postoperatively and subsequent spaced weaning. Elevated
      creatinine levels at follow-up were evaluated by renal transplant biopsy.
      Rejection was treated with steroids, reversal of weaning, addition of sirolimus,
      and/or antibody treatment, depending on grade of rejection. The mean duration of
      follow-up was 453 +/- 163 days after C 1H administration. Twenty-nine patients
      received C 1H for SRR and 11 patients for Banff 1B or worse rejections; 26
      patients received more than 1 dose of C 1H. Graft survival was 62.5% (25
      patients); 6 of the 15 allografts (40%) that failed had presented with rejections
      because of noncompliance. Graft survival in compliant patients with SRR or
      rejections equal to or worse than Banff 1B was 73.5% (25 of 34). Fourteen
      patients (35%) had infectious complications, of whom 2 patients (5%) died. C 1H
      is an effective agent for SRR and Banff 1B or worse rejections, with 95% patient
      survival and 73.5% graft survival (in compliant patients). The number of doses of
      30 mg C 1H should be restricted to two, as there is a high incidence of
      potentially fatal infectious complications.

PMID- 15848577
TI  - Deoxyspergualin prophylaxis with tacrolimus further improves long-term graft
      survival in living-related renal-transplant recipients transfused with donor
      specific blood.
AB  - BACKGROUND: We examined whether deoxyspergualin (DSG) prophylaxis in combination
      with cyclosporine (CsA)- or tacrolimus (Tac)-based immunosuppression augments the
      effect of donor-specific blood transfusions (DSTs) to improve long-term survival
      of living-related renal-transplants. METHODS: From May 1985 to January 1998, 176
      patients received DST from one-haplotype-identical donors prior to kidney
      transplantation. Group A (n = 64, 1985 to 1989) received CsA, prednisolone (PSL),
      antilymphocyte globulin (ALG), and azathioprine (AZA). Group B (n = 89, 1989 to
      1996) received CsA, PSL, ALG, and DSG. Group C (n = 23, 1996 to 1998) received
      Tac, PSL, ALG, and DSG, with DSG followed by AZA. Rejection episodes were
      classified as acute rejection (AR, within the first 3 months) or late acute
      rejection (LAR, from 4 months to 1 year). RESULTS: Five-year graft survivals were
      73.4%, 88.8%, and 91.3% for groups A, B, and C, respectively. The incidence of AR
      was 34%, 30%, and 13%, and that of LAR was 23%, 26%, and 30% for groups A, B, and
      C, respectively. There was no significant difference in the incidence of AR or
      LAR among the three groups. However, an elevated serum creatinine (sCr) > or =1
      mg/dL was observed in 73%, 15%, and 0% of patients during AR, and in 53%, 30%,
      and 14% during LAR for groups A, B, and C, respectively. These results suggest
      that the severity of AR or LAR was lowest among group C, contributing to the
      improved long-term graft survival in these patients. CONCLUSIONS: DSG prophylaxis
      with Tac-based immunosuppression further improves long-term graft survival among
      living-related renal-transplant recipients treated with DST by decreasing the
      severity of acute rejection episodes.

PMID- 15848578
TI  - Combined therapy of deoxyspergualin and plasmapheresis: a useful treatment for
      antibody-mediated acute rejection after kidney transplantation.
AB  - Antibody-mediated acute rejection (AbAR) is one of the primary causes of graft
      impairment in kidney transplant recipients. Deoxyspergualin (DSG), which displays
      an antiproliferative action against antigen-stimulated B cells inhibiting
      antibody production, may be effective to rescue AbAR in combination with
      plasmapheresis by suppressing antibody production and elimination. In the present
      study, we report our experience with DSG/plasmapheresis therapy for the treatment
      of AbAR. Five kidney transplant patients experienced a steroid-resistant acute
      rejection requiring dialysis followed by an AbAR that was confirmed by biopsy and
      flow cytometry crossmatch (FCXM) results. DSG was administration at 3 mg/kg per
      day for 10 days with plasmapheresis reduce antidonor antibody. Treatment outcome,
      effectiveness, and adverse events were examined; in two cases sequential FCXM
      examinations were performed to evaluate antibody status. All five patients
      received DSG/plasmapheresis therapy. The number of plasmapheresis treatments
      ranged from 1 to 9 according to treatment outcomes. Four patients recovered graft
      function following treatment; whereas one showed no response to the treatment,
      and the graft was lost. No serious side effects or infections were observed
      during or after treatment. Monitoring of sequential FCXM correlated with the
      clinical course. AbAR shows a worse prognosis than cellular rejection. It is
      refractory to conventional antirejection therapy. In the present study,
      DSG/plasmapheresis therapy was effective in four of five patients (80%) with
      AbAR. It may be considered the first choice of treatment for cases of acute
      humoral rejection.

PMID- 15848579
TI  - Fungal infections in transplant recipients receiving alemtuzumab.
AB  - Recently, we have used an anti-T-cell agent, alemtuzumab, as induction or
      conversion therapy to achieve a calcineurin (CNI) and steroid-free
      immunosuppressive regimen. We identified recipients who developed systemic fungal
      infections after the initiation of alemtuzumab and looked at their outcomes. The
      study population consisted of all pancreas transplant recipients who received
      alemtuzumab. Only invasive fungal infections were included in the analysis (eg,
      fungemia, meningitis, or pneumonia; fungal urinary tract infections were
      excluded). The organism was confirmed by culture, histopathology, or latex
      antigen test. Between February 2003 and February 2004, a total of 121 pancreas
      transplant recipients received alemtuzumab-56 as part of induction, and 65 as
      part of conversion. Of these, 8 (6.6%) developed an invasive fungal infection; 2
      (3.6%) recipients as part of induction therapy and 6 (9.2%) as part of conversion
      therapy. Mean recipient age was 42.1 years. The mean length of time from
      alemtuzumab administration (first dose) to the diagnosis of the fungal infection
      was 115.9 days (range 5 to 318). The organisms identified initially were:
      Cryptococcus, Histoplasma, Aspergillus, and Candida. Overall, 3 (38%) of the
      eight patients died during ongoing treatment of their fungal infection: two from
      sepsis, one due to myocardial infarction. The other five recipients were treated
      successfully and have functioning grafts. The initial therapeutic agents used
      included: amphotericin B/liposomal AMB (n = 6), voriconazole (n = 3), capsofungin
      (n = 2), and fluconazole (n = 1). The use of alemtuzumab as induction or
      conversion therapy in pancreas transplant recipients may predispose patients to
      the development of systemic fungal infections. It would be important to determine
      what the most appropriate prophylaxis regimen would be for these patients.

PMID- 15848580
TI  - Mycobacterial infections after kidney transplant.
AB  - We looked at mycobacterial infections occurring after a kidney transplant to
      determine incidence, risk factors, and outcomes. Of 3921 kidney transplants
      performed between 1984 and 2002, 18 (0.45%) (10 men, eight women; 11 cadaveric
      donor, seven living donor graft) were identified as having mycobacterial
      infection at some time posttransplant. Mean age at transplant was 38.3 years.
      Racial background was: Caucasian (n = 12), African-American (n = 2), Native
      Indian (n = 2), Hispanic (n = 1), and Middle Eastern (n = 1). The majority had a
      kidney alone (n = 14). Four recipients had simultaneous transplant of a second
      organ: pancreas (n = 2), islets (n = 1), and liver (n = 1). None of the 18
      recipients had documented mycobacterial infection pretransplant. One recipient
      had a positive Mantoux test at the time of transplant and then developed
      pulmonary tuberculosis 4 months posttransplant; the remaining 17 patients had
      either negative (n = 10) or unavailable (n = 7) pretransplant Mantoux results.
      Mean time to infection was 3.2 years (range 1 week to 12 years). The most common
      site of infection was respiratory (n = 8). Other sites included musculoskeletal
      (n = 4), skin (n = 3), gyn (n = 1), and other (n = 2). Only three of the
      infections were with mycobacterial tuberculi; the others were with avium (n = 5),
      chelonae (n = 2), or other nontuberculous mycobacteria. Risk factors included
      previous TB exposure, occupational exposure, or accidental soft tissue injury.
      Soft tissue infections often presented as chronic unhealed wounds and required
      extensive surgical debridements. With mean follow-up of 12.5 years since
      transplant and 9.2 years since infection, 13 of the recipients are alive and
      well; causes of death included cardiovascular (n = 3) and sepsis (n = 2).

PMID- 15848581
TI  - Natural history of hepatitis C virus infection in adult renal graft recipients.
AB  - AIM: To study the natural history of hepatitis C virus infection in renal
      transplantation, 464 HbsAg negative patients were prospectively studied from
      1989. METHODS: AntiHCV was tested by ELISA II and HCVRNA by Amplicor HCV RNA
      tests. RESULTS: Two hundred nine patients were antiHCV positive (C+). HCVRNA was
      confirmed in 89% of C+ patients. Compared with the 255 anti-HCV negative (C-), C+
      had undergone longer periods of dialysis (P = .0001), were more transfused (P =
      .01), and included more retransplants (P = .002). Immunosuppression was
      azathioprine (AZA) plus steroids in 133 and cyclosporine (CsA) in 331 patients.
      Liver biopsy showed chronic active hepatitis in 50, cirrhosis in 8, and fibrosing
      cholestatic hepatitis in 2 patients. Histologic progression of liver disease was
      confirmed in 18 of 26 patients. The causes of death in 84 patients (51 C+ vs 33 C
      ) were cardiovascular disease in 49%, sepsis in 13%, liver failure in 14%,
      neoplasia in 21%, and hepatocarcinoma in 2%. The 14-year patient survival was 75%
      in C+ and 86% in C- (P = .002). By multivariate analysis, age (>40) (P = .001)
      and C+ (P = .019) correlated with a worse patient survival. If patients were
      stratified according to age (<40 vs > or =40), younger C+ patients had a lower
      survival probability (P = .03). The 14-year graft survival was 44% in C+ vs 60%
      in C- patients (P = .001) but pure graft survival was similar (68% in C+ vs 72%
      in C-) (P = .13). CONCLUSION: The presence of C+ significantly reduced both
      patient and graft survival in the long-term with liver failure being the second
      most frequent cause of death.

PMID- 15848582
TI  - Outcomes of patients with rejection post-polyomavirus nephropathy.
AB  - INTRODUCTION: We sought to determine the effects of rejection in renal transplant
      recipients with polyomavirus nephropathy (PVN). METHODS: SCr, biopsy findings,
      BKV serum and urine loads (Taqman PCR), and BKV antibody titers (HA inhibition
      assay) were analyzed by two-sample median tests and z tests in 11 patients with
      median follow-up of 7.3 (2.0 to 31.5) months post-PVN. All patients underwent
      immunosuppression reduction (ISR) as PVN treatment. RESULTS: Post-PVN, 3 (27%)
      patients had five rejection episodes, with 80% being mild. Median time to
      rejection was 18 (2 to 60) weeks. One hundred percent of patients who experienced
      post-PVN rejection also experienced rejection pre-PVN. Rejection episode
      treatments consisted of: none in one, increased tacrolimus in two, IVIG in one,
      IVIG and increased tacrolimus in one. Median viral loads in patients with post
      PVN rejection versus those without rejection were not different in serum (2.01 x
      10(4) vs 9.00 x 10(4) BKV copies/mL; P = .22) or urine (5.37 x 10(5) vs 8.93 x
      10(6) BKV copies/mL; P = .28). Median BKV antibody titers were slightly lower
      (16384 vs 32768 HA units; P = .02) and median SCr values were significantly
      higher (2.7 vs 1.9 mg/dL, P = .0003) in patients who had experienced post-PVN
      rejection. Graft losses occurred in one rejection-free patient (chronic allograft
      nephropathy) and in one patient who experienced multiple acute rejection
      episodes, humoral rejection, and worsening PVN. CONCLUSIONS: Patients who
      experience rejection prior to PVN are at high risk of developing rejection post
      ISR and post-PVN; however, low graft loss rates may still be achieved.

PMID- 15848583
TI  - Human polyoma virus in kidney transplants: SV40 T-antigen demonstration in the
      urine.
AB  - We wanted to develop an immunostaining method of urine cytopreparations to detect
      polyoma virus infection by using fresh urine samples and staining with the
      monoclonal SV40 antibody and to compare the findings to the demonstration of
      decoy cells in the urine or to kidney histology. Routine urine samples from
      pediatric kidney transplant patients were collected either early after
      transplantation or later, cytocentrifuged, and immunostained with SV40-T
      antibody. The number of SV40-T-antigen-positive epithelial cells was counted in
      the cytopreparations and compared to the findings in routine urine cytology and
      transplant histology. Immunostaining of urine cytology with SV40-T-ab
      demonstrated clearly that the infected epithelial cells and the rate of infection
      could be estimated by semiquantitative counting. There was strong correlation
      between the findings in the urine and in the biopsies, but in the urine
      preparations the number of infected cells was much higher than in the biopsies.
      The high number of SV40-positive cells in the urine also correlated to the
      severity of clinical infection and to the state of transplant. Immunostaining of
      urine cytology with SV40-T-antibody seems to be useful in the diagnosis and
      follow-up of polyoma virus reactivation disease in transplant patients,
      especially in children with renal transplants.

PMID- 15848584
TI  - Polyoma BK virus reactivation in kidney and pancreas-kidney recipients.
AB  - BK virus infection has become important factor affecting graft function in renal
      transplant recipients. One of the most important complication of BK infection is
      nephropathy in patients after renal transplantation. The aim of this study was to
      evaluate incidence of BK reactivation and nephropathy in our population of renal
      allograft recipients. One hundred twelve renal or pancreas-kidney allograft
      recipients were included for the 24 months follow-up. The incidence of BK
      nephropathy was 7.85% and viremia 27.96%. In the second study group there were 28
      patients with graft function deterioration evaluated at the time of biopsy. In
      this group incidence of BK nephropathy was 7.1% and viral reactivation was
      diagnosed in 10.7% of patients. In our center, the incidence of BK nephropathy is
      the same as worldwide. The risk of BK virus replication is highest during first
      15 months after the surgical procedure.

PMID- 15848585
TI  - Treatment of cytomegalovirus infection or disease in solid organ transplant
      recipients with valganciclovir.
AB  - Valganciclovir (VGC) has proved efficacious and safe for the prophylaxis against
      cytomegalovirus (CMV) in high-risk transplant recipients and for the treatment of
      CMV retinitis in AIDS patients. We used VGC for the treatment of CMV infection
      (viremia without symptoms) or disease (CMV syndrome or tissue-invasive disease)
      in kidney, heart, and lung transplant recipients. Fourteen transplant recipients
      were treated: five for asymptomatic CMV infection and nine for CMV disease. VGC
      was administered in doses adjusted to renal function for 4 to 12 weeks (induction
      and maintenance therapy). Clinically, all nine patients with CMV disease
      responded to treatment. Microbiologically, treatment with VGC turned blood
      culture negative for CMV within 2 weeks in all patients and was associated with a
      > or =2 log decrease in blood CMV DNA within 3 weeks in 8 of 8 tested patients.
      With a follow-up of 6 months (n = 12 patients), asymptomatic recurrent CMV
      viremia was noted in five cases, and CMV syndrome noted in one case (all cases in
      the first 2 months after the end of treatment). VGC was clinically well tolerated
      in all patients; however, laboratory abnormalities occurred in three cases (mild
      increase in transaminases, thrombocytopenia, and pancytopenia). This preliminary
      experience strongly suggests that therapy with VGC is effective against CMV in
      organ transplant recipients; however, the exact duration of therapy remains to be
      determined: a longer course may be necessary to prevent early recurrence.

PMID- 15848586
TI  - Successful vaccination against varicella zoster virus prior to kidney
      transplantation.
AB  - BACKGROUND: In recent years we have observed a number of severe complications of
      primary varicella-zoster virus (VZV) infections after adult kidney
      transplantation. We questioned how many patients on the waiting list for kidney
      transplantation had not been protected against VZV and whether patients with
      renal insufficiency would be able to develop a specific immune response upon VZV
      vaccination. METHODS: We examined the VZV antibody titer of 280 patients on the
      kidney transplant waiting list. Seronegative kidney transplant candidates were
      vaccinated twice with a live attenuated varicella vaccine at an interval of 6
      weeks. CONCLUSIONS: Approximately 3% of patients on the waiting list were
      seronegative for VZV. Vaccination induced no side effects and resulted in a
      positive serologic response in most patients.

PMID- 15848587
TI  - Posttransplant lymphoproliferative disorder: significance of central nervous
      system involvement.
AB  - BACKGROUND: Few data exist regarding central nervous system (CNS) involvement in
      patients with posttransplant lymphoproliferative disorder (PTLD). The purpose of
      this study was to review the Israel Penn International Transplant Tumor Registry
      (IPITTR) experience with CNS involvement by PTLD. METHODS: Nine hundred ten PTLD
      cases from the United States were reported to the IPITTR and reviewed for CNS
      involvement. RESULTS: One hundred thirty-six transplant recipients with PTLD
      (15%) had CNS involvement. The highest incidence of CNS involvement occurred in
      pancreas (3 of 11; 27%) and kidney transplant recipients (76 of 429; 18%).
      Fifteen cases occurred in children and 121 cases in adults. For both children and
      adults, isolated CNS disease was associated with better survival when compared
      with multiple-site involvement (children: 29% vs 0%; adults: 12% vs 6%; P < .05).
      Three-year survival in PTLD patients with CNS involvement was 9.4% and without
      CNS involvement was 49.4% (P < .01). Radiation therapy alone appeared to provide
      the best survival rates (25%). CONCLUSIONS: CNS involvement in transplant
      recipients with PTLD carries an ominous prognosis; however, isolated CNS
      involvement has a better prognosis than CNS plus extracranial involvement.
      Radiation therapy alone provides the best results, but this may be a reflection
      of isolated CNS disease.

PMID- 15848588
TI  - Chemotherapy for posttransplant lymphoproliferative disorder: the Israel Penn
      International Transplant Tumor Registry experience.
AB  - INTRODUCTION: Very little published data exist regarding the results of
      chemotherapy treatment of posttransplant lymphoproliferative disorder (PTLD). The
      purpose of the study was to review the Israel Penn International Transplant Tumor
      Registry experience with PTLD treated with chemotherapy. METHODS: Patients with
      PTLD who received chemotherapy were identified and data collected regarding
      demographics, tumor characteristics, recurrence rates, and survival. RESULTS: One
      hundred ninety three solid organ transplant recipients with PTLD who received
      chemotherapy were identified. Most patients were male (142:51) and Caucasian
      (148; 16 AA, 29 unspecified). Most PTLD were B-cell predominant (81%), monoclonal
      (71), and CD 20+ (60% of patients tested). Organ transplanted included: kidney,
      92 (48%); heart, 54 (28%); liver, 30 (16%); pancreas, 8 (4%); and lung, 9 (5%).
      Median time to presentation posttransplant was 24.5 months (range 0.8 to 226.5
      months). Ninety patients received CHOP, 12 ProMACE, 65 other multidrug regimens,
      and 23 patients received single-agent chemotherapy. Five-year survival for these
      four regimens were: 24%, 25%, 32%, and 5%. PTLD-specific death rates were 34%,
      34%, 40%, and 48%. CONCLUSIONS: Single-agent chemotherapy appears to be inferior
      to other chemotherapy regimens for PTLD as it is associated with lower survival.

PMID- 15848589
TI  - Prostate cancer prior to solid organ transplantation: the Israel Penn
      International Transplant Tumor Registry experience.
AB  - INTRODUCTION: Prostate adenocarcinoma (PCA) is the second leading cause of cancer
      related deaths in men, and with routine prostrate specific antigen (PSA)
      screening, is being diagnosed with increasing frequency. To date, reported
      experiences with transplantation in men with a history of PCA are limited to only
      a few patients. This study presents the first series of transplant recipients
      with a history of PCA. METHODS: Analysis of transplant recipients with a history
      of pretransplant PCA was performed on the Israel Penn International Transplant
      Tumor Registry database. PCA were staged using American Joint Committee on Cancer
      criteria. Statistics analysis was performed by chi-square and Student t tests.
      RESULTS: Ninety patients with preexisting PCA were identified: 77 renal, 10
      heart, and three liver transplant recipients. Mean age at PCA diagnosis was 61.3
      +/- 6.3 years. Median interval between diagnosis and transplantation was 19.3
      months, and median follow-up after transplantation was 20.5 months. Median time
      to PCA recurrence was 10.6 months after transplantation and median survival time
      with recurrent PCA was 49.2 months after transplant. Patient mortality was 28.8%,
      and PCA-related death rate was 7.8%. PCA recurrence rate was 17.7%. Tumor
      recurrence rates in stage I and II disease (14 and 16%) were lower than in stage
      III disease (36%). CONCLUSIONS: In conclusion, death rate to disease other than
      PCA is three times that due to PCA. PCA recurrence rates are relatively low in
      patients who initially presented with stage I and II disease, and are half that
      of patients with stage III disease.

PMID- 15848590
TI  - De novo colorectal cancer: five-year survival is markedly lower in transplant
      recipients compared with the general population.
AB  - INTRODUCTION: The biological behavior of most solid tumors in transplant
      recipients has not been adequately compared to the general population. The
      purpose of the present study was to compare outcomes in de novo colorectal cancer
      (CRC) following solid organ transplantation to those observed in the general
      population (SEER) database. METHODS: All transplant recipients with de novo CRC
      in the Israel Penn International Transplant Tumor Registry were identified and
      analyzed and the data were compared to CRC patients in the SEER National Cancer
      Institute (NCI) database. RESULTS: One hundred and fifty transplant recipients
      with de novo CRC were identified, among which were 93 (62%) kidney, 29 (19.3%)
      heart, 27 (18%) liver, and 1 (0.7%) lung recipients. Median age of transplant
      recipients was 54 years, compared to a median age of 72 years for patients in the
      SEER NCI database. However, compared to patients from the SEER NCI database,
      recipients with Duke's A through C stage disease were noted to experience a
      significant decrease in 5-year survival. The results in Duke's C patients were
      particularly dismal. CONCLUSIONS: The early age at presentation of CRC in
      transplant recipients suggests that the development of de novo CRC may be
      effected by immunosuppression. Decreased 5-year survival rates in transplant
      recipients compared to the general population suggest that CRC in transplant
      patients is biologically more aggressive. These data cannot distinguish whether
      the lower survival rates are because the CRC are inherently biologically more
      aggressive or whether immunosuppression allows for more aggressive clinical
      behavior of CRC.

PMID- 15848591
TI  - Skin cancer following transplantation: the Israel Penn International Transplant
      Tumor Registry experience.
AB  - The purpose of this study was to analyze a large series of skin cancers in solid
      organ transplant recipients to determine their biologic behavior. METHODS: A
      retrospective review of all US transplant recipients with skin cancer reported to
      the Israel Penn International Transplant Tumor Registry was performed. RESULTS:
      Transplant recipients from the United States with skin malignancies were
      identified (n = 2018) and assigned to 1 of 3 groups: squamous cell cancer (SCC),
      basal cell cancer (BCC), or combined malignancies (BCC/SCC). Squamous cell to
      basal cell cancer ratio was found to be 1.9 to 1. The ratio of extrarenal to
      renal allograft recipients was identical for all 3 groups (3:1). The median
      interval from transplant to skin cancer diagnosis was greater than 4 years in
      each group and longest in those with isolated SCC lesions. In the SCC group,
      there was a 9% incidence of nodal or secondary site involvement affecting the
      cervix, perineum, or lung. The highest recurrence rate was demonstrated in the
      combined malignancy group. Cancer-specific deaths were significantly higher in
      the SCC (8%) and BCC/SCC (6.8%) groups compared to the BCC (3.6%) group.
      CONCLUSIONS: This large experience indicates that SCC is more common than BCC in
      transplant recipients. SCC alone or in combination with BCC appears aggressive
      and is associated with significant mortality.

PMID- 15848592
TI  - Regression of Kaposi's sarcoma in renal graft recipients after conversion to
      sirolimus treatment.
AB  - Kaposi's sarcoma (KS) is a rare complication of renal transplantation in Poland
      (in our center 2 of 1000 patients). Neovascularization (typical for KS) is
      promoted by KS-related vascular endothelial growth factor (t-r-VEGF). Sirolimus
      may reduce t-r-VEGF synthesis and inhibit PI3K-p70S6 kinase of endothelial cells.
      Two men, 58 and 51 years old, were transplanted in 2002. Initial
      immunosuppression consisted of cyclosporine, azathioprine, and prednisone. In the
      second patient, at the week 8 the immunosuppression was switched to tacrolimus
      and mycophenolate mophetil. KS symptoms appeared on hard palate and skin in month
      7 in both patients. In the first patient, the X-ray showed enlargement of
      mediastinal lymph nodes and diffuse interstitial infiltrates with nodular changes
      in both lungs. Serum creatinine of the first patient was increased from 1.6 to
      1.9 mg/dL, while in the second it remained stable (approximately 2.0 mg/dL).
      Since confirmation of KS immunosuppression has been minimized in both patients;
      all drugs except prednisone were withdrawn, and sirolimus was introduced (1-2
      mg/24 hours blood level 5-8 ng/mL). Within a month the progression of lung and
      skin disease ceased, and patients' conditions began to improve with lung
      opacities regressing, the biggest skin lesions diminishing and smaller ones
      disappearing. Within 1 year renal function improved. Our observation suggests
      that sirolimus-based immunosuppression proffers the possibility of KS regression
      with concomitant renal function preservation among renal graft recipients. It is
      difficult to ascertain whether KS regression may be attributed to sirolimus
      treatment or to the reduced overall immunosuppression.

PMID- 15848593
TI  - Kaposi's sarcoma in renal transplant patients: predisposing factors and
      prognosis.
AB  - Among 772 kidney transplant recipients in two centers 25 patients developed
      Kaposi's sarcoma (KS) (3.2%). The twenty-two of 25 recipients with regular follow
      up records were compared for predisposing factors with another group of 22 renal
      transplant recipients. All patients received cyclosporine (CsA), azathioprine, or
      mycophenolate mofetil and steroids; patients who received cadaver donor organs
      additionally received antilymphocyte globulin for induction. KS was diagnosed at
      a mean of 25.8 months after transplantation. The male to female ratio; mean age;
      mean follow-up period; hepatitis B, hepatitis C, cytomegalovirus status; and
      other infection rates were similar in the two groups. Some HLA-DR antigens were
      detected only in patients with KS. All patients had mucocutaneous involvement,
      which was multiple in 54.5%. Visceral involvement, and lymph node involvement, or
      both was detected in seven patients. First-line treatment was to stop CsA and
      reduce the doses of the other drugs. Three patients underwent additional surgical
      excision. Fourteen (63.6%) patients experienced complete remissions, including
      six who required additional chemotherapy or radiotherapy after incomplete or lack
      of responses to first-line treatment. Two patients died with functioning grafts
      due to generalized KS. Seven patients returned to hemodialysis at a mean of 36
      months after the diagnosis of KS. No significant predisposing factor was observed
      other than the prevalence of specific HLA-DR antigens. Chemotherapy or
      radiotherapy should be initiated for patients with multiple, diffuse, and rapidly
      progressive lesions or organ dysfunction in addition to withdrawal of CsA and
      tapering of other drugs. Generalized KS displays the poorest prognosis.

PMID- 15848594
TI  - Mutation scanning of the p53 tumor suppressor gene in renal and liver transplant
      patients in Hungary.
AB  - INTRODUCTION: The increased incidence of malignancies among transplanted patients
      is well known. Abnormal function of the p53 tumor suppressor gene has been
      reported in more than half of all tumors. The aim of our study was to detect
      point mutations of p53 gene in transplanted patients because the presence of
      mutations may be a predictive factor for tumor development. An earlier diagnosis
      can help to develop new strategies for immunosuppressive therapies. METHODS:
      Three point mutations were chosen based on the literature: exon5-codon175, exon7
      codon248, exon8-codon273. Genomic DNA from the plasma of 60 liver, 362 renal
      transplants, and 45 nontransplanted patients with different tumors and 20
      suspected healthy patients were analyzed with a real-time PCR method using the
      Roche LightCycler. The mutations were evaluated by melting curve analysis.
      RESULTS: We elaborated a special protocol for scanning the above mentioned p53
      point mutations, which were proved by sequencing as well. Among 487 patients, 486
      showed a wild-type genotype. The only patient carrying a mutation at codon 273
      (heterozygous) was a liver transplant patient, who developed pancreas carcinoma
      and had already died. CONCLUSION: Our data suggest that mutations of the targeted
      codons in leukocyte DNA seem to be rare, but a mutation could be lethal. The
      evaluated three point mutations of p53 gene were not predictive for tumor
      development.

PMID- 15848595
TI  - Parathyroidectomy for parathyroid carcinoma in renal transplantation.
AB  - INTRODUCTION: Hyperparathyroidism (HPT) is a highly prevalent pathology in the
      chronic renal disease population, which is associated with considerable
      morbidity, and mortality. The histopathological findings most often reported are
      solitary adenoma, diffuse hyperplasia, and autonomous hyperplasia. Carcinoma is
      an unusual cause of primary parathyroid hyperfunction (0.5% to 4% according to
      data); in renal transplanted patients it is exceptional. We sought to analyze
      parathyroid gland histology from renal transplant patients in comparison with
      nontransplanted patients and to report a parathyroid carcinoma case in a renal
      transplant patient. METHODS: We retrospectively analyzed parathyroidectomies
      (PTX) and histopathological reports between March 1989 and December 2003.
      RESULTS: Among 72 PTXs 41 were performed because of primary HPT; 26, secondary
      HPT; and five, tertiary HPT. Among the 41 primary HPT cases there were two
      carcinomas (4.88% primary HPT operated patients), one of whom was in a kidney
      transplant recipient. Among the total number of surgeries, seven were performed
      in six renal transplant patients, including five diffuse hyperplasia cases; one,
      nodular hyperplasia with an adenoma focus; and one, parathyroid carcinoma.
      CONCLUSIONS: Parathyroidectomy indications in the renal transplant population are
      usually associated with the clinical picture of tertiary HPT, which does not
      resolve after a functional renal transplant. In spite of this, diffuse
      hyperplasia, which is associated with secondary HPT, was the most frequent
      hystological finding. Two carcinomas were observed: one in a renal transplant
      patient (16.6% parathyroidectomies) and the other in a patient who did not show
      renal failure. These data coincide with international records.

PMID- 15848596
TI  - Hypothesis: epithelial-to-mesenchymal transition is a common cause of chronic
      allograft failure.
AB  - Renal, hepatic, and lung allografts are compromised by aggressively deteriorating
      function. This chronic process is produced by an overall burden of organ damage,
      but the pathophysiology remains poorly understood. Rates of chronic rejection in
      the lung, for example, have not substantially improved over the last decade,
      despite new immunosuppressive drugs and improvements in surgical procedure. We
      present a hypothesis that epithelial-to-mesenchymal transition is a common cause
      of chronic allograft failure. Research in this area may provide insights into
      chronic rejection of kidney, liver, and lung allografts that impact on future
      therapeutic strategies.

PMID- 15848597
TI  - Loss of peritubular capillaries in the development of chronic allograft
      nephropathy.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) remains the most important cause
      of late renal graft loss. In this study, we examined the role of peritubular
      capillary (PTC) injury in the development of CAN. METHODS: We studied renal
      biopsies (n = 79) obtained from grafts with CAN. PTC injury was examined
      morphologically by immunohistochemistry for CD34. These findings were correlated
      with interstitial fibrosis and graft dysfunction. Humoral immunity involved in
      CAN was studied by C4d staining. RESULTS: The CAN cases in the present study
      included chronic rejection (CR) (n = 14, 17.8%) and C4d-positive chronic humoral
      rejection (CHR; n = 6, 42.9% in CR cases). Irrespective of CR, CHR, or other CAN,
      the development of CAN was characterized by injury to and loss of identifiable
      PTCs, accompanied with the development of interstitial fibrosis. In CR and CHR
      cases, the loss of PTCs was prominent and seemed to progress within a relatively
      short period after transplantation. A decrease in the number of PTCs
      significantly correlated with the development of interstitial fibrosis (r = 
      0.75, P < .001) and impairment of graft function (r = -0.69, P < .001).
      CONCLUSIONS: Irrespective of whether CR, CHR, or other factors contribute to CAN,
      the processes involved in its development appear similar and are characterized by
      progressive injury and loss of PTCs, with the development of renal scarring.
      Immunohistochemistry for CD34 in human renal biopsies is a useful method for the
      detection of microvascular injury.

PMID- 15848598
TI  - Analysis of allograft biopsy specimens in renal transplants with proteinuria: is
      proteinuria a culprit of graft loss?
AB  - It has been proposed that proteinuria occurring after renal transplantation may
      be not only a marker but also a culprit of allograft dysfunction. We
      retrospectively analyzed the data from 55 patients who underwent transplant renal
      biopsy for proteinuria and/or azotemia occurring beyond 1 year after
      transplantation. Proteinuria was considered as significant when > or = 30 mg/dL,
      and the results of transplant biopsy were categorized according to the Banff 97
      classification. Logistic regression was used to estimate odds ratios (OR) for
      graft loss associated with proteinuria and transplant pathology. The patients
      were followed for 86.0 +/- 32.8 months after transplantation, and transplant
      biopsy was performed at 54.1 +/- 31.0 months. Proteinuria at 1 year after
      transplantation noted in 29.1% of patients was not significantly associated with
      graft loss (OR = 1.94, 95% CI from 0.59 to 6.41). In addition, proteinuria at the
      time of transplant biopsy was not significantly associated with graft loss.
      Chronic allograft nephropathy was the most frequent transplant pathology. Only
      glomerulonephritis was significantly associated with proteinuria at the time of
      the transplant biopsy. On the other hand, graft loss was significantly associated
      with the presence of proteinuria both at 1 year after transplant biopsy and at
      the final follow-up. These results suggest that posttransplantation proteinuria
      is an important marker of graft dysfunction, but is not predictive of graft loss
      in biopsy-proven cases. Appropriate management guided by the results of a
      transplant biopsy may improve the outcome.

PMID- 15848599
TI  - Tubular and glomerular proteinuria in diagnosing chronic allograft nephropathy
      with relevance to the degree of urinary albumin excretion.
AB  - The diagnosis of chronic allograft nephropathy (CAN) is based on pathological
      examination according to Banff 97 schema. The aim of the study was to evaluate
      the usefulness of tubular and glomerular proteinuria for noninvasive recognition
      of CAN. One hundred and thirty renal allograft recipients (at least 90 days after
      transplantation) who had undergone diagnostic allograft biopsy were included in
      the study. Beta2-microglobulin, alpha1-microglobulin, albumin, immunoglobulin G,
      total protein, and creatinine concentrations were obtained from the second
      morning urine specimen. Raw data and values calculated per 1 g of creatinine
      excreted in urine along with time after transplantation, serum creatinine, and
      its change over a period of 2 months prior to biopsy were taken for analysis.
      Urine proteins were measured using a nephelometric method. Statistical
      calculations were performed using MANOVA and stepwise discriminant analysis
      (SDA). Statistical diagnosis and staging of CAN matched the pathological method
      in 68% of a preliminary SDA. Therefore patients were divided into
      normoalbuminuric, microalbuminuric, and macroalbuminuric groups. There was no
      significant differences between protein excretion, except alpha1
      microglobulinuria (CAN 0 vs 2, P = .018; CAN 1 vs 2, P = .041), beta2
      microglobulinuria (CAN 0 vs 2, P = .026; CAN 1 vs 2, P = .0033), and total
      proteinuria (CAN 0 vs 2, P = .042) in the normoalbuminuric group. Nevertheless,
      diagnoses obtained using SDA were 89%, 91%, and 92% identical to the results of
      pathological examinations, for normoalbuminuric, microalbuminuric, and
      macroalbuminuric groups, respectively. In conclusion, tubular and glomerular
      proteinuria measurements may be useful for a noninvasive CAN diagnosis and
      staging only with regard to degree of urinary albumin excretion.

PMID- 15848600
TI  - Renoprotective effect of early inhibition of the renin-angiotensin system in
      renal transplant recipients.
AB  - The aim of this work was to study the effect of early administration of
      angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II type-I
      receptors blockers (ARB) on renal function and proteinuria in renal transplant
      recipients with good, stable renal function and mild proteinuria. Twenty four
      patients started ACEI/ARB therapy within 14 months after surgery (RAS-). Before
      (T0) and every month for 2 years after the initiation of ACEI/ARB we evaluated
      creatinine clearance (CrCl), proteinuria/day (UP), UP/CrCl (FUP), arterial blood
      pressure, and serum lipid levels. Twenty-eight patients who never received
      ACEI/ARB (RAS+) were studied in the same fashion. In the RAS+ CrCl was reduced
      after 2 years compared with T0 (64.5 +/- 2.6 vs 75.0 +/- 3.2 mL/min, P < .003);
      UP and FUP were both significantly increased (666 +/- 65 vs 132 +/- 20 mg/day 8.8
      +/- 1.2 vs 2.6 +/- 0.6 mg/mL x 10(3); P < .001 and .002) compared with T0.
      Moreover, UP (P < .04), FUP (P < .03), and the percentage reduction of CrCl
      (11.4% +/- 5% vs 4.6% +/- 1.8%; P < .05) were greater in RAS+ than RAS- subjects
      at 2 years of the study. The values of other parameters did not show significant
      differences between the two groups. In conclusion, this study suggested that
      ACEI/ARB have renoprotective effects, when used in patients with good stable
      renal function and mild proteinuria. These drugs may play a role to prevent
      chronic allograft nephropathy.

PMID- 15848601
TI  - Inhibition of plasminogen activator inhibitor-1 by angiotensin II receptor
      blockers on cyclosporine-treated renal allograft recipients.
AB  - INTRODUCTION: We previously showed that proteinuria from a renal graft was
      significantly decreased by administration of losartan potassium, an angiotensin
      II receptor blockers (ARB). To further evaluate the mechanism, we performed
      another clinical study focusing on the change in plasma plasminogen activator
      inhibitor-1 (PAI-1) levels among cyclosporine (CyA)-treated renal allograft
      recipients. METHODS: Among 12 hypertensive CyA-treated kidney transplant
      patients, four received 25 to 50 mg/day of losartan; four, 4 to 8 mg/day of
      candesartan cilexetil; and another four, 20 to 40 mg/day of nifedipine. Four CyA
      treated kidney-transplanted patients without hypertension were selected as a
      control group. Informed consent was obtained from all participants. PAI-1 and
      serum creatinine (S-Cr) levels were monitored every 3 months for 1 year. RESULTS:
      Considering the pretreatment of PAI-1 as 100%, the mean percent of PAI-1 at 1
      year after the onset of study for losartan, candesartan, nifedipine, and control
      groups were 78.6 +/- 6.7%, 81.4 +/- 8.0%, 96.7 +/- 7.6%, and 110.4 +/- 9.2%,
      respectively. The ARB groups demonstrated significant differences from the
      control group (P < .01), while the nifedipine group did not. S-Cr levels among
      ARB-administered groups were increased slightly but temporarily. As for S-Cr
      levels, no significant differences were seen among the four groups. CONCLUSIONS:
      Control of hypertension itself is important for all renal graft recipients;
      however, PAI-1 reduction by ARBs was thought to be a key for renal preservation.
      We expect that ARBs will contribute to prolonged renal allograft survival.

PMID- 15848602
TI  - Blood pressure and graft outcome in renal transplantation.
AB  - To investigate the effects of blood pressure (BP) on kidney function, we reviewed
      116 patients who had a median follow-up of 40.5 months. Systolic and diastolic
      hypertension (HTN) at month 6 resulted in significantly higher serum creatinine
      (SCr) levels at 1 year, compared with patients with normal BP, namely, 2.2 versus
      1.4 mg/dL (P = .0001) and 1.87 versus 1.5 mg/dL (P = .04), respectively. Mean
      systolic and diastolic BP at the end of 1 and 6 months were significantly higher
      among patients who had returned to hemodialysis or who had an SCr > or =2 mg/dL
      at their last follow-up. Mean age, mean donor age, donor type, and sex had no
      significant effect on graft function. Patients receiving Rapamune-based treatment
      (n = 9) had no graft failure; graft outcomes were similar between cyclosporine
      based and tacrolimus-based immunosuppression therapy. Patients with biopsy-proved
      acute rejection showed significantly lower graft survival. By multivariate
      analysis, systolic HTN at the end of 1 month (P = .006) and 6 months (P = .01),
      and diastolic HTN at the end of 6 months (P = .04) were independent risk factors
      for graft outcome. Actuarial 5-year graft survival was 95%, versus 76% in
      patients with normal BP versus systolic HTN at 1 month, respectively (P = .02). A
      significant difference in 5-year graft survival was observed between patients
      with normal diastolic BP and diastolic HTN at 6 months (95% versus 67%,
      respectively; P = .001). Since systolic and diastolic BP at different times
      before and after transplantation correlate with graft function, more attention
      should be paid to maintain normal BP in patients with renal transplants.

PMID- 15848603
TI  - Immediate conversion from tacrolimus to cyclosporine in the treatment of
      posttransplantation diabetes mellitus.
AB  - Posttransplantation diabetes (PTDM) is a frequent complication of tacrolimus
      (TAC)-based immunosuppressive therapy after kidney transplantation. We
      investigated whether immediate conversion from TAC to Cyclosporine (CSA) could
      reverse or at least improve new-onset PTDM. Between February 2002 and February
      2004, 28 adult kidney transplant recipients maintained on TAC were diagnosed with
      new-onset PTDM. Eight adult patients with new-onset PTDM were enrolled in the
      study and converted from TAC to CSA, the remaining 20 patients served as controls
      and were continued on the TAC-based immunosuppression. The conversion to CSA was
      performed immediately after establishing the diagnosis of PTDM at an average of
      11 months posttransplantation. We did not document any episodes of acute
      rejection or worsening renal function after conversion. After conversion to CSA,
      among the 3 patients started on insulin, 1 has come completely off antidiabetic
      medications, whereas 1 required decreased doses of insulin, and the third has
      been converted to oral medications. Of the 5 patients originally on oral
      medications, 3 completely discontinued therapy, whereas the other 2 were well
      controlled on single-drug therapy at reduced doses. After a mean follow-up of 17
      months, in the control group 9 of the 16 patients started on oral antidiabetics
      ultimately required insulin treatment and no patient could stop antidiabetic or
      insulin therapy. These findings indicate that conversion from TAC to CSA is a
      simple, safe, and efficacious way to reverse or at least improve PTDM.

PMID- 15848604
TI  - Prospective, multicenter, randomized trial to compare incidence of new-onset
      diabetes mellitus and glucose metabolism in patients receiving cyclosporine
      microemulsion versus tacrolimus after de novo kidney transplantation.
AB  - New-onset diabetes mellitus (NODM) is associated with increased risk of graft
      failure and death in renal transplant recipients. Some clinical studies have
      indicated that NODM risk is higher with tacrolimus than cyclosporine, but no
      comparative trial has used American Diabetic Association (ADA)/World Health
      Organization (WHO) criteria for diagnosis of diabetes mellitus. The Diabetes
      Incidence After Renal Transplantation, Neoral C2 Monitoring Versus Tacrolimus
      (DIRECT) study is a 6-month open-label, multicenter trial comparing the impact of
      tacrolimus and Neoral (cyclosporine microemulsion) on glucose metabolism in 700
      de novo kidney transplant recipients, based on ADA/WHO criteria. Patients are
      randomized to tacrolimus (C0 monitoring) or Neoral (C2 monitoring), stratified by
      baseline diabetic status and ethnicity. All patients receive basiliximab,
      corticosteroids, and mycophenolate mofetil or enteric-coated mycophenolate acid
      (myfortic). Pooled interim 3-month results from a subset of 115 patients
      receiving either tacrolimus or Neoral showed that the primary efficacy end-point
      (biopsy-proven acute rejection [BPAR], graft loss or death) occurred in 11
      patients (10%). There were four graft losses and only one death, which occurred
      after graft loss. Eight patients experienced BPAR (7.3%). Among 99 patients who
      were nondiabetic at baseline, 14 developed NODM by month 3, 17 developed impaired
      fasting glucose or impaired glucose tolerance, and another 5 patients received
      hypoglycemic treatment for at least 14 consecutive days or at the month 3 visit,
      resulting in a 36% incidence of impaired glucose metabolism. At 3 months, median
      GFR (Nankivell) was 63.7 mL/min; median serum creatinine was 137 micromol/L. Full
      complete results are expected in December 2005.

PMID- 15848605
TI  - Are anemic patients more sensitive to calcineurin inhibitors?
AB  - A calcineurin inhibitor (CNI) is characterized by high affinity binding to red
      blood cells. There is a possibility that hematocrit levels might affect the
      immunosuppressive effects of cyclosporine (CsA). The purpose of this study was to
      examine whether the treatment with CNI was more effective in preventing acute
      rejection in anemic compared with nonanemic patients and to find a suitable
      method to monitoring immunosuppression. Ninety-five living donor renal transplant
      recipients who were treated with CsA were divided into five groups depending on
      their Ht levels. The incidences of biopsy-proven acute rejection were 1/8
      (12.5%), 8/31 (25.8%), 6/28 (21.4%), 10/22 (45.5%), and 2/6 (33.3%) for Ht < or =
      25%, 25% < Ht < or = 30%, 30% < Ht < or = 35%, 35% < Ht < or = 40%, and 40% < Ht,
      respectively. In vitro IL-2 mRNA inhibition tests were performed to evaluate
      lymphocyte function after stimulation of whole-blood with phorbol myristate
      acetate and Ca-ionophore in the presence of various concentrations of CsA. Whole
      blood CsA levels causing 50% inhibition of IL-2 mRNA (IC50) were 256, 310, 175,
      and 55 ng/mL for Ht 50%, 40%, 30%, and 20%, respectively. It is speculated that
      plasma concentrations of CsA may increase at low Ht levels, because lower
      incidences of acute rejection and lower IC50 values of CsA were observed in the
      anemic state. When the dosage of CsA was adjusted to its whole-blood
      concentration, the anemic state is likely to enhance the immunosuppressive effect
      of CsA. A pharmacodynamic study, such as the IL-2 mRNA inhibition test, is
      preferable for CsA monitoring.

PMID- 15848606
TI  - Iron deficiency--an underrecognized problem in nonanemic and erythrocytic kidney
      transplant recipients: risks and effects of ACEI and of iron treatment.
AB  - The state of iron deposits in long-term kidney graft recipients is not well
      known. Angiotensin enzyme inhibitors (ACEIs) reduce hematocrit levels in patients
      with posttransplant erythrocytosis (PTE), but their action on iron deposits has
      not been sufficiently evaluated. We designed this study to investigate the
      prevalence of iron deficiency among patients without anemia, the efficacy of ACEI
      treatment and its influence on iron deposits, and the risks of iron treatment in
      patients with symptomatic iron deficiency but no anemia. One hundred thirty eight
      patients were included if they had a kidney transplant for more than a year, with
      good renal function, with no anemia, and with neither iron nor rHuEpo, ARA, or
      ACEI treatment. One hundred seventeen had a normal Ht (group 1) and 21 had PTE
      (group 2). Iron deficiency was found in 73 (62.4%) group 1 patients and in 10
      (47%) group 2 patients. Two group 1 patients with symptoms of iron deficiency
      were treated with oral iron. Their symptoms disappeared, but one developed PTE.
      Enalapril treatment decreased Ht levels in PTE but not in control patients.
      Furthermore, this drug increased iron deposits in PTE and controls with a
      baseline iron deficiency. We conclude that there is a high prevalence of iron
      deficiency in long-term transplanted patients without anemia. Furthermore, iron
      treatment must be carefully administered because of the risk of PTE. Enalapril
      treatment decreased Ht levels in PTE but not in control patients and increased
      iron deposits in patients with baseline iron deficiency.

PMID- 15848607
TI  - Predictive factors of postrenal transplant anemia.
AB  - OBJECTIVE: The aim of our study was to identify independent factors that might
      predict anemia at 6 months' (M6) and 12 (M12) months' posttransplantation.
      Postrenal transplant anemia was defined as a hemoglobin (Hb) level below 13 g/dL
      for men, and below 12 g/dL for women. We included 99 renal transplants performed
      in our department in 2001, for whom the graft was still functioning at 1 year.
      RESULTS: Anemia was observed in 78%, 35.5%, and 25% on day (D) 0, and at M6, and
      M12, respectively. Iron deficiency was observed in 14% of patients at D0, and 13%
      at M12. During the postoperative period, 59.8% of patients received at least one
      blood transfusion, whereas 37% of patients were prescribed recombinant
      erythropoietin (rEpo) therapy within the first few months posttransplantation. By
      multivariate analysis the independent predictive factors for anemia at M6 were
      rEpo therapy at D0, initial nephropathy, posttransplantation rEpo therapy,
      hematocrit at M3, platelets at D7 and sirolimus therapy. The independent
      predictive factors for anemia at M12 were rEpo therapy at D0 and platelets at D7,
      delayed graft function (DGF), serum creatinine, and creatinine clearance at M12,
      and Hb level at M6 were also checked. CONCLUSION: The prevalence of anemia is 25%
      at M12; DGF, renal function at M12, and anemia at M6 were independent risk
      factors of anemia at M12.

PMID- 15848608
TI  - Influence of angiotensin-converting enzyme polymorphism gene, IGF-1, and other
      factors in the response rate of hematocrit to enalapril treatment in patients
      with posttransplant erythrocytosis.
AB  - A significant relationship between hematocrit values and serum parameters such as
      the insulin like growth factor (IGF-1) and calcium was observed in patients with
      posttransplant erythrocytosis (PTE). Since angiotensin-converting enzyme
      inhibitors (ACEI) decrease hematocrit (Ht) levels in these patients, ACE genotype
      should play an important role. We designed this study to investigate whether ACE
      genotype or baseline concentrations of IGF-1, IGF-blood binding protein 3 (BP3),
      growth hormone (GH), or Ca influenced the response of Ht to ACEI treatment.
      Twenty-one kidney graft recipients with PTE were treated with enalapril (2.5 to 5
      mg/d) for 1 year. IGF-1, BP3, GH, Ca, and Ht were determined before as well as
      15, 30, 90, 180, and 365 days after enalapril treatment. ACE polymorphism was
      also determined. Enalapril treatment significantly decreased Ht levels. Only IGF
      1 baseline levels showed a positive correlation to the decreased Ht (P < .025).
      ACE genotype as determined in 18 patients, showed no correlation with the
      response to enalapril. Patients with ACE genotype II showed a tendency to an
      earlier display of PTE. We conclude that low doses of enalapril decrease Ht
      levels in PTE patients; that PTE begins earlier in patients with II ACE genotype;
      and that only IGF-1 baseline levels influence the Ht decrease after treatment.
      These observations suggest that ACEI decrease the Ht via an inhibitory effect on
      IGF-1, which has a stimulary effect on erythropoiesis.

PMID- 15848609
TI  - Changes in bone mineral density and selected metabolic parameters over 24 months
      following renal transplantation.
AB  - Our aim was to evaluate changes in serum levels of selected bone metabolism
      indicators and bone density over 24 months following renal transplant. A partial
      objective was assessment of the effectiveness of prophylactic administration of
      vitamin D and calcium preparations to prevent progression of osteopathy after
      kidney transplantation. Forty patients after kidney transplantation were
      prophylactically given vitamins A and D (800 IU) and calcium (1000 mg) a day.
      During monitoring, the serum creatinine in all recipients was <200 micromol/L
      (subgroup A with creatinine concentration < 120 micromol/L versus subgroup B with
      creatinine 120 to 200 micromol/L). The concentration of serum parathormone, serum
      level of bone fraction of alkaline phosphatase, serum concentrations of
      phosphorus and calcium urinary 24-hour excretion of phosphorus and calcium were
      examined at 2 weeks and 2 years after transplantation. In the same time period,
      radiographs of thoracic, lumbar spine, and hip joints were obtained. Bone density
      (BMD) of the lumbar (L) spine and the hip was determined by dual-energy X ray
      (Lunar Prodigy). Two years after transplantation in subgroup A, the BMD showed
      decrease in 80% of recipients in the L spine area but hip showed a 15% BMD
      increase. In subgroup B, the BMD decreased in 95% recipients in L and hip and
      only 25% showed a BMD increase. No clinical or radiographic sign of fracture was
      detected in this group. We conclude that prophylactic administration of vitamin D
      and calcium is not sufficient to prevent the progression of osteopathy after
      renal transplantation. Changes in bone density evaluated after the kidney
      transplantation are affected by graft function.

PMID- 15848610
TI  - Evaluation of cortical bone by peripheral quantitative computed tomography in
      renal transplant recipients.
AB  - BACKGROUND: The absolute risk of fractures in renal transplant patients is 3
      times that of matched controls. Most of the symptomatic fractures are peripheral,
      suggesting a greater compromise of cortical bone. Peripheral quantitative
      computed tomography (pQCT) is a new imaging technique that allows separate
      noninvasive evaluations of cortical and trabecular bones. We investigated
      cortical bone by pQCT in 12 renal transplant patients (seven men and five women)
      for comparison with 27 normal controls. METHODS: pQCT (XCT 960, Stratec,
      Pforheim, Germany) was performed upon the distal radius of the nondominant
      forearm (15% the length of the ulna, proximal from the radius end plate). We
      evaluated total and cortical bone mineral density (TBMD, cBMD), total (cross
      sectional) and cortical area (TA, cA), cortical thickness (cThk), endosteal and
      periosteal circumferences, and the buckling ratio (r/cThK). RESULTS: Compared
      with normal controls transplant patients as a whole showed a significant increase
      in TA, in endosteal circumference (P < .001), and in the buckling ratio (P <
      .001) with a significant reduction in cThK (P < .001). Female patients had a
      marked decrease in cA (51.4 vs 69.3 [pixel n]; P < .0001) and cThK (2.08 vs 2.78
      mm; P < .0001). Male patients also had a decrease in cThK (2.54 vs 3.30 mm; P =
      .0001) and an increase in endosteal perimeter (31.2 vs 26.4 mm; P < .0001). Total
      time on dialysis prior to renal graft correlated negatively with cortical
      thickness (r = .62; P < .01). CONCLUSIONS: Our results suggest that a marked
      thinning of cortical bone may explain the increased incidence of peripheral
      fractures among renal transplant patients.

PMID- 15848611
TI  - Influence of vitamin D receptor gene polymorphisms on secondary
      hyperparathyroidism and bone density after kidney transplantation.
AB  - Secondary hyperparathyroidism and immunosuppressive treatments are the most
      important pathogenetic factors for bone disease after kidney transplantation. The
      aim of study was to compare the influence of vitamin D receptor (VDR) genotype on
      the PTH level and bone mineral density (BMD) in 67 patients, including 45
      immunosuppressed with cyclosporine (CsA) and 22 with tacrolimus (Tac) versus 147
      healthy volunteers. Two VDR polymorphisms: BsmI and FokI were assayed with RFLP
      PCR. Scantibodies were utilized to evaluate 1-84 PTH. BMD was measured by DEXA.
      Hormone levels were measured on the third day and sixth month after
      transplantation. BMD was examined at the third and ninth month. The distribution
      of FokI genotype differed, but the BsmI genotypes did not differ between the
      transplant patients and the control group. All transplanted patients showed an
      elevated tPTH at the first examination. The highest PTH values, which were
      observed in bb genotype, significantly decreased after the transplant procedure.
      Patients with the FF genotype who were treated with CsA showed higher levels of
      tPTH than those with the Ff genotype. At 6 months, a decrease in tPTH occurred in
      both the CsA and the Tac patients. A low BMD at the third month was more frequent
      among patients of the BB genotype treated with CsA. The Z-score remained low at
      the third month and at the ninth month. In conclusion, kidney graft recipients
      show overrepresentation of the Ff genotype. Our preliminary data suggest that the
      bb genotype exhibits a protective effect on bone loss after renal
      transplantation.

PMID- 15848612
TI  - Increased risk of hemorrhagic complications in renal allograft recipients
      receiving systemic heparin early posttransplantation.
AB  - The aim of this paper is to document the risk of hemorrhagic complications in
      renal allograft recipients requiring systemic heparinisation within the first 2
      weeks posttransplantation. METHODS: A retrospective chart review of 326 RA
      recipients from January 1998 to July 2003 was subjected to statistics by SPIDA
      with P values <.05 considered significant. RESULTS: 16/326 (4.9%) recipients were
      initiated on intravenous (IV) heparin within the study period. Enoxaparin was
      subsequently used in 10/16 (62.5%) of these recipients. Intravenous heparin was
      instituted at a median 8 (1-14) days posttransplantation. Hemorrhagic
      complications occurred in 10/16 (62.5%) recipients on IV heparin versus 11/310
      (3.5%) nonanticoagulated RA recipients (P = .0001). Hemorrhage occurred at a mean
      9.75 (2-43) days into the course of IV heparin. The median peak APTT 24 hours
      prior to hemorrhage in RA recipients on heparin was 68.5 (58-180) versus a median
      peak APTT of 70 (50-140) among recipients on heparin who did not sustain a
      hemorrhagic complication (P = .30). A major intervention (predominantly surgery)
      was required in 6/16 (37%) recipients on IV heparin versus 7/310 (2.2%)
      nonheparinised RA recipients (P < .0001). Enoxaparin was instituted at a mean
      22.5 (4-55) days posttransplantation. Delayed hemorrhage subsequently occurred in
      4/10 (40%) recipients on enoxaparin. In conclusion, major and minor hemorrhagic
      complications occur more commonly among recipients requiring early post
      transplant IV heparin. Hemorrhage occurred despite APTT monitoring with APTT
      levels tending to be similar in RA recipients with versus without complications.
      Delayed hemorrhage was also seen with the subsequent use of enoxaparin.

PMID- 15848613
TI  - Weight gain after living-related renal transplantation affects long-term graft
      function.
AB  - Weight gain is a common problem in renal transplant recipients. This study
      investigated whether weight gain after living-related renal transplantation
      affects long-term graft function. The cohort included 93 patients (28 females, 65
      males of mean age, 33.78 +/- 9.78 years who were recipients of kidneys from
      living-related donors. The data set related risk factors to occurrence of chronic
      allograft nephropathy (CAN): namely, number of HLA mismatches, PRA levels,
      delayed graft function, acute rejection, suboptimal immunosuppression,
      hypertension, hyperlipidemia, and size mismatch. Patients with a 10% increase in
      body mass index sustained throughout at least 2 years posttransplantation were
      categorized as group 1 (abnormal weight gain; n = 65) and the others were
      categorized as group 2 (no or normal weight gain; n = 28). Chronic allograft
      nephropathy was more frequent among group 1 (P < .03). The mean times to CAN
      diagnosis in groups 1 and 2 were 1053.41 +/- 461.86 days and 1128.57 +/- 416.09
      days, respectively (P > .05). Of all the risk factors for CAN, occurrence of
      acute rejection was the most important (OR = 5.39, 95% CI: 2.07 to 14.03, P <
      .001). When this factor was excluded, weight gain emerged as the most important
      risk factor (OR = 3.04, 95% CI: 1.01 to 9.69, P < .04). There were no significant
      differences between the groups with respect to the frequencies of immunologic and
      nonimmunologic risk factors (P > .05 for all). The results suggest that excessive
      weight gain after living-related renal transplantation may be an additional risk
      factor for development of CAN. Patients should pay attention to diet and control
      weight gain after transplantation.

PMID- 15848614
TI  - Treatment of hypercholesterolemia with ezetimibe in the kidney transplant
      population.
AB  - BACKGROUND: Given the high incidence of lipid abnormalities, high burden of
      cardiovascular disease, and high proportion who do not achieve target levels
      despite therapy in the kidney transplant population, additional lipid lowering
      strategies are needed. METHODS: This was a nonrandomized, open-label, single
      cohort evaluation of ezetimibe, a novel cholesterol absorption inhibitor, in 40
      stable kidney transplant recipients with hypercholesterolemia. RESULTS: After 4
      weeks of therapy total and LDL cholesterol were reduced by 23 +/- 13% (P < .0001)
      and 33 +/- 15% (P < .0001), respectively. The drug was equally effective in
      patients on cyclosporine (19), tacrolimus (13), or sirolimus (8), but more
      effective (P = .0006) when used in combination with a statin (41 +/- 13%
      reduction in LDL, n = 22) compared with monotherapy (24% +/- 13%, n = 18). There
      were no significant effects on serum creatinine, drug levels, body weight, or
      liver function tests. CONCLUSIONS: Ezetimibe is an effective LDL cholesterol
      lowering agent in the kidney transplant population. Further studies are warranted
      in a larger population not only to examine the extent of cardiovascular risk
      reduction but also to detect unwarranted toxicity.

PMID- 15848615
TI  - Cyclosporine and tacrolimus: influence on cardiovascular risk factors.
AB  - After allogenic transplantations, a dramatic increase in the development of
      arteriosclerotic plaques can be observed, which might be due to metabolic
      alterations, changes in the transplant organ, or the immunosuppression regimen.
      Many studies have demonstrated beneficial effects of tacrolimus compared with
      cyclosporine with regard to these conditions. These results have suggested that
      conversion to tacrolimus from cyclosporine is advantageous. Our study
      investigated whether patients with deteriorating renal function profit from this
      conversion. Thirty renal transplant patients were studied retrospectively, using
      data recorded from 3 years before to 3 years after conversion from cyclosporine
      to tacrolimus. While renal function (GFR) deteriorated progressively under
      cyclosporine, it stabilized and even improved under tacrolimus (creatinine:
      DeltaCyc = +1.4 mg/d; DeltaTac = -0.7 mg/dL; GFR: DeltaCyc = -35 mL/min; DeltaTac
      = 14 mL/min). In addition, uric acid levels (7.0 mg/dL vs 6.4 mg/dL, P < .05) and
      cholesterol levels (258 mg/dL vs 225 mg/dL, P < .05) were both significantly
      lower under tacrolimus. Conversion from cyclosporine to tacrolimus is recommended
      for kidney transplant patients in whom there has been a progressive fall in renal
      function. It leads to stabilization or even improvement of transplant function
      and a reduction in cardiovascular risk factors.

PMID- 15848616
TI  - Cardiovascular effects of successful renal transplantation: a 30-month study on
      left ventricular morphology, systolic and diastolic functions.
AB  - The purpose of this study was to determine the effects of a successful renal
      transplantation on left ventricular (LV) morphology, systolic and diastolic
      function. Forty-three renal transplant patients prospectively studied by
      echocardiography (30 months follow-up) were divided into two groups. The first
      echocardiographic examination was performed 3.0 +/- 2.8 months after renal
      transplantation in group I (11 men, 12 women); and 34.4 +/- 29.1 months after
      transplant in group two (9 men, 11 women). We noticed the following changes in
      blood pressure (BP): group 1 systolic BP reduction (from 140.5 +/- 23.6 to 126 +/
      6.8 mmHg; P < .01), and pulse pressure reduction (from 59.5 +/- 14.9 to 47.5 +/-
      9.8 P < .05); group 2, diastolic BP acceleration (from 78.4 +/- 8.7 to 84 +/- 6.9
      mmHg, P < .05). LV mass index decreased in group 1 (from 126.4 +/- 18.0 g/m2 to
      104.6 +/- 15.9 g/m2, P < .05). The incidence of LV hypertrophy (LVH) decreased in
      group 1 from 70% to 40% (P < .05). Only one parameter of systolic function-end
      systolic stress-significantly decreased in both groups: group 1 from 78 +/- 11 to
      61 +/- 12 g/cm2; group 2 from 63.8 +/- 9.0 to 55.1 +/- 9.0 g/cm2, P < .05). The
      pattern of mitral inflow changed: in group 1, the normal pattern decreased from
      30% to 20% and the restrictive pattern increased from 0% to 10%; in group 2, the
      normal mitral inflow pattern decreased from 60% to 20% and abnormal relaxation
      type increased from 40% to 80%. Regression of LVH after renal transplant improved
      LV geometry and systolic function. Despite better systolic function a progression
      of LV diastolic dysfunction was noticed, which might be explained by cyclosporine
      treatment. Renal transplantation exerted a beneficial impact on cardiomyopathy
      manifested by LVH and systolic dysfunction.

PMID- 15848617
TI  - A simple cardiovascular risk score can predict poor outcome in non-heart-beating
      donor renal transplantation.
AB  - A simple cardiovascular risk score used in our centre to plan cardiovascular work
      up for renal transplantation can predict outcome in non-heart-beating donor
      (NHBD) renal transplantation. Patients in the higher-risk group, with a score of
      >12 of a maximum of 36 are likely to have a longer duration of delayed graft
      function, poorer glomerular filtration rate at 6 months, and inferior graft and
      patient survival, together with a relative rate of graft loss within 60 days of
      4.514 (P = .019) and within 1 year of 3.511 (P = .036). Although a high
      cardiovascular risk score should not be regarded as a contraindication to NHBD
      transplantation, the score can be used to facilitate recipient selection.

PMID- 15848618
TI  - Efficacy and safety of Palmaz stent implantation in the treatment of renal artery
      stenosis in renal transplantation.
AB  - To verify the long-term efficacy and safety of Palmaz stent implantation in the
      treatment of transplant renal artery stenosis (TRAS), we reviewed the charts of
      26 patients affected by TRAS and treated by percutaneous transluminal angioplasty
      (PTA) followed by permanent insertion of a Palmaz stent. The mean follow-up
      period was 43.31 +/- 33.6 months. The mean blood pressure fell significantly at 1
      month after stenting (118 +/- 8.1 vs 101 +/- 7.8 mmHg; P < .0001); then remained
      stable. Renal artery blood flow, as determined by Doppler ultrasonography, was
      reduced from 352.5 +/- 56.5 to 157.3 +/- 53.7 cm/sec at 1 month after stenting (P
      < .0001). Renal function improved after stenting (serum creatinine 2.2 +/- 1.4
      mg/dL preinsertion versus 1.72 +/- 1.05 at 3 years). In conclusion, in cases of
      severe or recurrent TRAS, stenting of the renal artery has proved to be an
      effective therapeutic tool. This method, which has low procedure costs and an
      extremely low complication rate has proved to be safe and to offer the potential
      of preserving luminal patency, improving the long-term efficacy of percutaneous
      angioplasty.

PMID- 15848619
TI  - Renovascular reconstruction of grafts with renal artery variations in living
      kidney transplantation.
AB  - INTRODUCTION: The shortage of grafts in living kidney transplantation has forced
      the use of marginal grafts with arterial disease or grafts with multiple renal
      arteries (MRA). We reviewed the outcomes of transplants using allografts with MRA
      procured by open donor nephrectomy and report two cases requiring vascular
      reconstruction. PATIENTS AND METHODS: We reviewed 31 cases where renovascular
      reconstruction of an MRA graft was performed. A ex vivo pantaloon (side-to-side)
      anastomosis to create a common channel was performed in 24 cases including two
      cases of renal artery aneurysms in the grafts, where vascular reconstruction was
      performed in the same fashion after resection of the aneurysm. In four cases, an
      accessory artery was anastomosed sequentially after revasculization of the main
      artery. In three cases of grafts with multiple renal arteries, multiple
      anastomoses were done in situ after various ex vivo renovascular reconstructions.
      RESULTS: Twenty one MRA grafts including grafts with a renal aneurysm are
      functioning well for a mean follow-up 135 months. The graft survival rate was
      71.0% at 5 years after transplantation and 67.7% at 10 years. The donors whose
      grafts had a renal aneurysm were also well and normotensive with normal renal
      function at present. Ten grafts failed mainly due to chronic allograft
      nephropathy. CONCLUSION: MRA grafts procured by open nephrectomy, including those
      with renal artery aneurysms, were engrafted successfully by applying appropriate
      renovascular surgery. The use of those grafts was safe for both the recipient and
      the donor.

PMID- 15848620
TI  - Effect of routine insertion of a double-J stent after living related renal
      transplantation.
AB  - It is still not clear whether double-J stents (DJS) are of benefit. We sought to
      determine whether routine prophylactic use of DJS reduced postoperative
      complications after renal transplantation. We prospectively evaluated 42 living
      donor renal transplantations performed between September 2001 and September 2003.
      The patients were randomly assigned to one of two groups: 21 operations (group
      1), included a DJS placed during Lich-Gregoir ureterocystotomy and 21 cases
      (group 2), a Lich-Gregoir ureterostomy without DJS insertion. Among group 1, the
      DJS were removed within the first month after transplantation. One patient in
      group 1 (5%) developed a urinary leakage. In group 2, there was one case of
      delayed graft function (5%) and one patient developed a hematoma (5%) at the
      operative site. The group rates for urinary tract infection were not
      significantly different (P > .05). In the early postoperative period, a renal
      biopsy was performed if a patient's creatinine level was elevated or remained
      elevated during 3 days after transplantation. Four patients in group 1 and 10
      patients in group 2 required a renal biopsy (P = .04). All four of the group 1
      biopsies and three of the group 2 specimens revealed acute rejection. The other
      seven group 2 biopsies showed tubuloepithelial injury. We suggest that ureteral
      stasis may cause tubuloepithelial injury and slow down the decrease in creatinine
      levels. In our model, the DJS did not increase urinary tract infections but
      provided a smooth decline in creatinine levels, which may reduce the question of
      acute rejection.

PMID- 15848621
TI  - Ureteric complications of renal transplantation: the impact of the double J stent
      and the anterior extravesical ureteroneocystostomy.
AB  - The urological complications of renal transplantation are well documented. In
      1990, our experience of 507 consecutive renal transplants using the Leadbetter
      Politano technique, which was unsplinted in the vast majority of patients, had a
      ureteric complication rate of 7.7%. Here, we report the long-term incidence and
      management of our ureteric complications in 1186 consecutive renal transplants
      done over the following 11 years using an extravesical onlay stented
      ureteroneocystostomy. We report a considerable reduction in the urological
      complications of renal transplantation to 3.8%. Furthermore, we were able to use
      percutaneous radiological techniques to salvage the majority (84.7%) of ureteric
      complications. Recourse to surgery was required rarely but enabled salvage of all
      treatment failures.

PMID- 15848622
TI  - Computerized CT-based 3D visualization technique in living related liver
      transplantation.
AB  - INTRODUCTION: For living donor liver transplantation (LDLT) accurate diagnostic
      workup is essential. Multiple imaging approaches are currently used. Problems
      arise in the assessment of vascular and bile duct anatomy, liver graft volume,
      and vascular territories involved. A 3D visualization system that improves
      anatomic assessment, allows interactive surgery planning, and acts as an
      intraoperative guide with enhanced precision is required. Refinements in computed
      tomography (CT) technology with the introduction of multidetector-row CT scanners
      and implementation of mathematical methods on computerized digital data has
      enabled CT-based 3D visualizations. MATERIALS AND METHODS: Sixteen LDLT
      candidates and three LDLT recipients were assessed by multislice CT examination.
      Image processing of the digital raw data for 3D visualization included
      segmentation and calculation of center lines. A hierarchical mathematical model
      representing the vascular and biliary tree was created. This allowed calculation
      of individual vascular territories. RESULTS: 3D CT-based visualization in LDLT
      facilitates diagnostic workup with high accuracy for analyses of vascular and
      bile duct variants, volumetry, and assessment of the optimal surgical splitting
      line of the living donor liver. Resultant areas of either arterial
      devascularization or venous congestion can be displayed and quantified
      preoperatively. The diagnostic method is of major impact on patient selection and
      directly influences intraoperative surgical guidance. The currently practiced
      "multiple imaging approach" approach, especially with regard to invasive
      diagnostics, can be avoided in the future.

PMID- 15848623
TI  - The main hepatic anatomic variations for the purpose of split-liver
      transplantation.
AB  - BACKGROUND/AIMS: Variant hepatic anatomy must be recognized and appropriately
      managed during split-liver transplantation to ensure complete vascular and
      biliary supply to both grafts. The aim of this study was to demonstrate the
      importance of an assessment of the hepatic anatomical structures for the purpose
      of split-liver transplantation. MATERIAL AND METHODS: Human cadaveric livers (n =
      60) were obtained during routine autopsies. The cadavers and the livers had to
      comply with the following requirements: (1) minimum age 18 years, (2) no liver
      pathology expected from medical history, and (3) no liver pathology noted at
      autopsy. Resections were carried out en bloc with liver, celiac trunk, left
      gastric artery, lesser omentum, superior mesenteric artery, and head of the
      pancreas. The main anatomical structures of the liver as hepatic artery, portal
      vein, biliary tree, and hepatic veins were dissected and correlated hepatic
      segments for the application of liver splitting. RESULTS: The right the median,
      and the left hepatic veins were unique, with in 59 (98.3%), 53 (88.3%) and 46
      (76.3%) cases, respectively. The portal vein trunk divided into right and left
      branches in 59 (98.3%) cases. A median branch appeared in 9 (15.2%) cases and no
      bifurcation of the portal vein occurred in 1 (1.6%) case. The right and left
      hepatic ducts were multiple in 47 (78.3%) and 57 (95%) cases, respectively,
      however, the median, hepatic duct was unique in 16 (26.6%) cases. Examining the
      intrahepatic distribution of the right hepatic duct, we found 4 branches in 28
      (59%) cases (segments V, VI, VII, and VIII) 2 branches in 11 (23%) cases,
      (segments V and VI) and 2 branches in 8 (17%) cases (segments VII and VIII).
      Fifty-seven cadavers had multiple left hepatic ducts. The intrahepatic dissection
      showed that the distribution of the major branches were toward hepatic segments
      II and III. Three separate branches of the left hepatic duct were found in 11
      (19%) cases (segments II, III, and IV). Two intrahepatic ducts coming from
      hepatic segments V and VI drained separately into the left intrahepatic biliary
      tree in 1 (2%) case. The arterial supply of the liver was by right and left
      hepatic artery with only 9 (15%) cases there being median hepatic artery. The
      right hepatic artery, coming from the superior mesenteric artery, was present in
      15 (25%) cases and a left hepatic artery originating from the left gastric artery
      in only 2 (3.3%) cases. The left hepatic artery had 2 exceptional origins, in 1
      (1.6%) case coming directly from the abdominal aorta and in the other from the
      superior mesenteric artery. The right and left hepatic artery was accessory, in
      11 (18.3%) and 2 (3.3%) cases, respectively. The right hepatic artery was
      dominant in 4 (6.6%) cases. The median hepatic artery was directed to segment IV
      in 6 (10%) cases and to segment II and III in 3 (4.9%) cases. CONCLUSION: The
      study showed that the technique of controlled liver splitting for transplantation
      in 2 recipients is an acceptable method to increase the number of liver
      allografts. The anatomical and technical details of the splitting procedure are
      critical for the success of this technique. Good graft function and avoidance of
      complications depend on each graft having an intact arterial and portal blood
      supply as well as biliary and venous drainage from all retained liver segments.
      The absence of a bifurcation of the portal vein is a rare anomaly and would
      certainly contraindicate a partition.

PMID- 15848624
TI  - Anatomic variation of the right hepatic artery and its reconstruction for living
      donor liver transplantation using right lobe graft.
AB  - We analyzed the anatomy and reconstruction of the right hepatic artery (RHA) in
      96 cases of adult-to-adult living donor right liver transplantations, during
      2002. Most right livers had a single orifice (n = 185, 96%). Seven right livers
      (4%) showed multiple arteries, namely a replaced artery in five cases and
      accessory arteries in two cases. Three liver grafts had two separate orifices:
      both arterial stumps were reconstructed in one case, and accessory arteries were
      ligated in two cases because of sufficient back bleeding. The mean diameter of
      the graft RHA was 2.4 mm (1-4). More than 60% (59 of 96) of graft arteries were
      anastomosed with distal branches of recipient RHA for size matching. Eleven graft
      arteries were anastomosed to vessels other than the RHA, namely the left hepatic
      artery [LHA] in eight right gastroepiploic artery in three: for size matching in
      five and due to previous injury of RHA in six. Five cases showed significant size
      mismatches of more than twofold. The median follow-up period was 270 days. In one
      patient, an intramural thrombus developed on postoperative day 3 requiring a
      revision of the anastomosis. In another patient, arterial stenosis occurred on
      postoperative day 16 a time when collateral arteries had developed. The overall
      complication rate related to arterial reconstruction was 2%. In conclusion, with
      precise knowledge of the anatomy, an adequate selection of recipient arterial
      stump, and an experienced technique, a desirable result may be achieved in right
      lobe transplantation.

PMID- 15848625
TI  - Imaging of hepatic arterial anatomy for depicting vascular variations in living
      related liver transplant donor candidates with multidetector computed tomography:
      comparison with conventional angiography.
AB  - AIMS: The aim of this study was to evaluate liver arteries to depict variations
      by using multidetector computed tomography (CT) in donor candidates for living
      related liver transplantation. METHODS: Computed tomographic hepatic angiography
      was carried out using a multidetector 16-row CT scanner (Sensation 16; Siemens)
      in 48 candidates between April 2003 and August 2004. Multidetector CT was
      performed after intravenous injection of 150 mL of contrast material at a rate of
      4 mL/s. Arterial phase images were acquired after contrast injection. Afterward,
      maximum intensity projections and volume-rendered images were produced from the
      axial image data. Twenty-eight of these patients underwent conventional catheter
      angiography. RESULTS: Excellent arterial opacification was shown on multidetector
      CT scans in all patients; arteries up to tertiary branches were identified with
      CT. Of 28 patients who had both multidetector CT angiography and conventional
      angiography, only a branch of hepatic artery originating from superior mesenteric
      artery that supplied the posterior segment of the right lobe was not identified
      on multidetector CT angiography. In 27 donors, hepatic arterial anatomy depicted
      at multidetector CT angiography was identical to that at conventional
      angiography. We identified hepatic vascular variants in 22 of 48 patients with
      multidetector CT. The most common arterial variant was an accessory hepatic
      artery arising from the left gastric artery. CONCLUSIONS: Preoperative imaging
      evaluation of hepatic vascular anatomy is crucial for surgical planning in living
      related transplant donors. Multidetector CT is useful to depict hepatic arterial
      anatomy with high accuracy.

PMID- 15848626
TI  - Changes in serum levels of growth factors in healthy individuals after living
      related liver donation.
AB  - INTRODUCTION: To obtain better insight into the kinetics of hepatic growth
      factors following partial hepatectomy for living related liver donation, we
      investigated the postoperative changes in serum levels of hepatocyte growth
      factor (HGF), epidermal growth factor (EGF), vascular epidermal growth factor
      (VEGF), and transforming growth factor-alpha (TGF-alpha). PATIENTS AND METHODS:
      Eighteen healthy donors undergoing right hepatectomy for living related donation
      were enrolled in this study. Serum levels of HGF, EGF, VEGF, and TGF-alpha were
      measured using enzyme-linked immunosorbent assay kits before surgery, at 2 hours
      after resection, and daily during 5 days postoperatively. RESULTS: Mean
      preoperative HGF serum levels in healthy adults were 778 +/- 64 pg/mL. Within 2
      hours after operation, they significantly increased to 9608 +/- 3111 pg/mL
      afterward decreasing to 2726 +/- 241 at day 1 and 2283 +/- 250 pg/mL at day 2.
      Hereafter HGF serum levels stabilized at increased levels until day 5 (2109 +/-
      138, 2047 +/- 219, 2283 +/- 336 pg/mL, respectively). At all time points, the
      differences between pre- and postoperative HGF levels were significant (P < .01).
      In contrast, VEGF and EGF serum levels showed no significant differences between
      pre- and postoperative levels at all time points. TGF-alpha was not detected
      using a commercially available test with a detection limit of 10 ng/mL,
      suggesting only low TGF-alpha serum levels following liver resection. CONCLUSION:
      Significantly increased HGF serum levels after hepatectomy demonstrate its
      crucial role among the other investigated growth factors in regeneration of the
      remnant liver tissue during the early period after the operation.

PMID- 15848627
TI  - Domino liver transplantation in living donors.
AB  - Domino liver transplantation (DLT) has been developed as a method to expand the
      donor pool. In living donors DLT, the prime concern is to avoid any disadvantage
      to the donor and the first recipient. Seven DLTs were performed among 211
      patients who underwent living donor liver transplantation. The domino recipients
      included six with hepatocellular carcinoma and one with citrullinemia. The domino
      grafts were obtained from patients with familial amyloid polyneuropathy (FAP)
      including the left liver in three cases and the right liver in four. Among the
      seven domino recipients, a 64-year-old woman with advanced hepatocellular
      carcinoma died of lung metastasis. The other six domino recipients are alive
      without FAP symptoms. In living donor liver transplantation, because the vessels
      of the graft from the first donor are not long enough for anastomosis, the
      hepatic vessels must be left as long as possible when removing the liver from the
      FAP patients in order to ensure sufficient safety for vascular reconstruction.
      With careful decision making during the procedure, such as where to divide the
      vessels in the FAP patients, DLT may help address the shortage of liver grafts.

PMID- 15848628
TI  - Results of 132 hepatectomies for living donor liver transplantation: report of
      one death.
AB  - AIMS: Liver transplant is the primary therapy for patients with end-stage liver
      disease. Its high success rates have lead to a broadening of the indications for
      liver transplantation, resulting in an increasing shortage of donors. Living
      donor liver transplantation has become an option to overcome waiting list
      mortality. We describe our experience with hepatectomy for living donor liver
      transplantation and report a case of death. METHODS: Patients (n = 132) underwent
      hepatectomy for living donor liver transplantation from June 2000 through June
      2004. A 4-phase preoperative evaluation was performed on all patients, whose ages
      ranged from 13 to 54 years (mean = 29.7 +/- 8.1 years). Of the 132 patients, 76
      patients (57.5%) underwent left lateral segmentectomy, 33 patients (25%)
      underwent left lobectomy, and 23 patients (16%) underwent right hepatectomy. In 2
      other patients (1.5%), a monosegment (segment II) was obtained after left lateral
      segmentectomy. RESULTS: Twenty patients (15%) experienced a complication, the
      most common being incisional hernia, pneumonia, and biliary fistulae. On the
      seventh postoperative day, 1 patient developed a fatal cerebral hemorrhage while
      recovering from mild liver dysfunction. CONCLUSIONS: Although living donor liver
      transplantation is generally safe, serious and fatal complications may occur.

PMID- 15848629
TI  - Decision-related factors and attitudes toward donation in living related liver
      transplantation: ten-year experience.
AB  - INTRODUCTION: Living related liver transplantation (LRLT) has been performed
      since 1994 in Korea; more than 600 donors have contributed to our successful LRLT
      program for 10 years. Although the decision to donate is difficult and the donors
      need a formal psychosocial assessment, no system has been available to us for the
      assessment. This survey was performed as a presurveillance for the development of
      a psychosocial assessment protocol. METHODS: A survey questionnaire included 31
      questions on general and medical characteristics, factors, and processes related
      to the decision for donation. Donors of partial livers at least 6 months ago
      during the period from December 1994 to August 2003 and whose address could be
      confirmed by telephone were enrolled in the study. RESULTS: A questionnaire was
      sent by mail to 441 contactable donors of whom 209 (47.4%) responded. Male-to
      female ratio was 2:1 and mean age was 32.8 years (range: 16 to 60 years). The
      number of spousal donors was 120 (57.4%) and 164 (78.5%) donors were employed at
      the time of donation. Protestants, Buddhists, and Catholics were 29.2%, 19.1%,
      and 14.8%, respectively. Parents were the most common recipients (33.0%),
      followed by siblings (17.2%), extended family members (17.2%), and children
      (15.8%); one hundred eighty nine (90.4%) donors had decided by themselves, the
      major reason for donation in 192 (91.9%) donors was "to save the lives of family
      members and relatives." The first person who suggested donation was the donor
      (64.1%), followed by family members (23.9%) or the attending physicians (8.6%).
      Although 70.8% of donors answered that they were not hesitant to donate at the
      time of decision, 44.5% were uneasy at the possibility of being unable to sustain
      a normal life after donation, at their lack of knowledge on organ donation, and
      about the pain and fear of surgery. Family members and relatives (53.3%), medical
      personnel (46.7%), and previous donors (35.4%) were the preferable counselors
      compared to transplantation institutions and clergymen. The large majority
      (80.8%) of donors would encourage others to donate. CONCLUSIONS: Although the
      decision to donate was made by the donors themselves in most cases and they
      appeared firm and determined about their decision, a significant number of donors
      felt uneasy about possible complications of organ donation and effects on their
      lives after donation. A precise and formal psychosocial assessment protocol is
      needed to support and secure their decision before and after donation.

PMID- 15848630
TI  - Liver transplantation in fulminant hepatic failure: experience with 40 adult
      patients over a 17-year period.
AB  - INTRODUCTION: To evaluate the influence of pretransplantation recipient and donor
      prognostic factors on graft-patient survival. MATERIALS AND METHODS: Between
      April 1986 and June 2003, 40 liver transplantation (LT) procedures to treat
      fulminant hepatic failure were performed (5.7%). Twenty-one pre-LT recipient and
      donor variables were retrospectively considered for analysis. RESULTS: The
      indications for LT were hyperacute (62.5%), acute (35%), and subacute hepatic
      failure (2.5%). Glasgow Coma Scale scores ranged from <5 in 22 patients to > or
      =5 in 18 patients. The causes were hepatitis B (n = 21), unknown (n = 10),
      Amanita phalloides (n = 5), and other (n = 4). The 1-year graft and patient
      survival rates were 48.3% and 61.3%, respectively. Perioperative and late
      mortality was 27.5% and 22.5%. The only variable statistically significant for
      graft survival was waiting list time for LT <48 hours (P = .05). DISCUSSION:
      Liver transplantation is the best treatment for fulminant hepatic failure, with a
      1-year patient survival rate of 61.3%. The short waiting list time has an
      important role in outcome.

PMID- 15848631
TI  - The effect of albumin dialysis on cytokine levels in acute liver failure and need
      for liver transplantation.
AB  - In acute liver failure (ALF), detoxification capacity of liver cells is reduced
      and a variety of cytokines, immune modulators, and toxic substances are
      accumulating. Multiple organ failure in ALF has been associated with increased
      blood cytokine levels. We have used a blood purification system, molecular
      adsorbent recirculating system (MARS), which is based on removal of both protein
      bound and water-soluble substances and toxins in liver failure. In this study, we
      measured the effect of MARS therapy on plasma cytokine levels in 49 patients with
      ALF. Interleukin 6 (IL-6), IL-8, IL-10 and tumor necrosis factor (TNF)alfa were
      determined immediately before and after the first MARS therapy and after the last
      session using enzyme-linked immunosorbent assays. The overall survival of these
      ALF patients was 82% at 6 months; the native liver recovered in 26 cases, and 14
      were successfully transplanted. All three interleukins were increased before the
      MARS treatment but only anti-inflammatory IL-10 was reduced significantly during
      therapy, which in this setting could be interpreted as a positive effect. We were
      not able to show constant decreases in proinflammatory cytokines, but only
      transient effects on IL-8 and IL-6. Surprisingly TNFalfa level was normal and did
      not change during therapy. In theory, MARS albumin dialysis may remove toxic
      substances from the blood circulation and thereby improve the possibilities of
      the liver to recover; however, of the measured cytokines only IL-10 decreased
      significantly.

PMID- 15848632
TI  - Use of recombinant factor VIIa in pediatric patients with liver failure and
      severe coagulopathy.
AB  - BACKGROUND: Several reports have suggested a benefit for recombinant Factor VIIa
      (rFVIIa) in nonhematological conditions, including liver disease and
      transplantation. However, there are few reports of its use in children with liver
      failure. Recently, we used rFVIIa in four patients with liver failure and severe
      coagulopathy with bleeding who demonstrated significant laboratory and clinical
      improvement following its use with no side effects. PATIENTS AND METHODS: All
      four patients were hospitalized with liver failure, coagulopathy, and bleeding
      that was controlled with fresh frozen plasma, platelets, and other therapies, as
      indicated. Their international normalization ratios (INR) ranged from 1.7 to 5.8
      (normal 0.9-1.1). All four patients received rFVIIa for bleeding episodes that
      were not responding to their usual therapy, for procedures with a high risk of
      bleeding, or both. The dose of rFVIIa ranged from 0.067 to 0.3 mg/kg. The INR
      improved to normal or near normal in all four patients. In all cases, bleeding
      stopped within 10 minutes of receiving the rFVIIa, and there were no
      complications observed. CONCLUSIONS: rFVIIa provided significant benefit in these
      children with liver failure and severe coagulopathy, in terms of clinical and
      laboratory improvement in their bleeding and coagulation profiles. There were no
      obvious side effects from the rFVIIa. This drug may be an important tool in the
      treatment of children with liver failure and more study is needed to define the
      optimal dosing for children.

PMID- 15848633
TI  - Comparison of two different percutaneous splenic artery interventions in the
      treatment of hypersplenism: preliminary report.
AB  - BACKGROUND: Splenomegaly and hypersplenism occur in patients with chronic liver
      disease and liver transplant recipients. The traditional treatment for
      hypersplenism is surgical removal. Percutaneous interventional methods, such as
      partial splenic embolization, are alternatives to surgery for hypersplenism. This
      article gives preliminary findings for a new percutaneous technique in which a
      narrowed stent is placed in the splenic artery. METHODS: The study focused on 10
      patients (eight males and two females) who were treated for hypersplenism.
      Partial splenic embolization was performed in six patients (age range, 1-43
      years) who were waiting for liver transplantation, and narrowed stents were
      placed in four patients (age range, 12-47 years) who had undergone either
      orthotopic two patients) or heterotopic two patients) liver transplantation. For
      embolization, the splenic artery was catheterized and polyvinyl alcohol particles
      were infused to the distal branches, reducing blood flow in the spleen by 40% to
      50%. In the other cases, a narrowed stent was deployed to the middle portion of
      the splenic artery. RESULTS: Hypersplenism was successfully treated in all 10
      cases. Compared with partial splenic embolization, placement of narrowed stents
      was associated with lower frequencies of postintervention fever and pain, shorter
      hospital stay, and decreased need for antibiotics. In addition to treating
      hypersplenism, narrowed-stent placement also completely resolved splenic artery
      steal syndrome in the two patients (orthotopic liver transplant recipients) with
      this condition. CONCLUSION: Percutaneous placement of a narrowed stent in the
      splenic artery is a promising new technique for treating hypersplenism and
      splenic arterial steal syndrome.

PMID- 15848634
TI  - DR antigens influence graft outcome and HCV recurrence after liver
      transplantation.
AB  - Hepatitis C (HCV) recurrence following liver transplantation is universal.
      However, the severity of recurrence is highly variable between patients. We
      speculated that recipient DR antigens or the level of DR mismatching between the
      recipient and the donor might affect the severity of HCV recurrence and allograft
      survival. Clinical outcome was compared between HCV+ recipients with DR2, DR3, or
      DR5 versus HCV+ recipients with all other DR antigens. Recipients with DR3 had
      reduced allograft survival (P < .02), a higher rate of HCV recurrence (P < .05),
      and more severe liver disease (P < .05). Recipients with DR5 had superior
      allograft survival (P < .05), low rates of HCV recurrence (P < .05), and benign
      liver disease (P < .05). Clinical outcome of recipients with DR2 was equivalent
      (P = Ns) to the non-DR2, -3, -5 recipients. The incidence of acute rejection was
      equivalent (P = Ns) in all groups. The level of DR mismatching between donor and
      recipient did not affect HCV recurrence or severity. However, allograft survival
      was better (P < .05) in recipients with zero DR mismatches. The data show that
      host genetic factors play an important role in HCV recurrence and allograft
      outcome after liver transplantation. In addition, identification of DR antigens
      may help predict an HCV+ patient's relative risk for severe HCV recurrence.

PMID- 15848635
TI  - Multiple organ failure caused by end-stage liver disease successfully treated
      with living donor liver transplantation using perioperative percutaneous
      cardiopulmonary support: a case report.
AB  - A 54-year-old female diagnosed with primary biliary cirrhosis (PBC) 10 years
      earlier was referred for a living donor liver transplant (LDLT). During her
      workup, she developed pulmonary edema and respiratory failure due to aspiration
      pneumonia, which required artificial ventilation. The PaO2/FiO2 (P/F) ratio at
      that time was 60. Although continuous hemodiafiltration (CHDF) and plasma
      exchange (PE) were initiated, improvement in the P/F ratio was limited to 133. As
      transplantation was the only approach to save this patient, we performed LDLT
      using a right lobe graft aided by percutaneous cardiopulmonary support (PCPS).
      The graft weight was 650 g and the graft weight/recipient weight ratio was 1.6%.
      During LDLT, the patient's cardiopulmonary function was stable with PCPS, and the
      surgical procedure was completed without complications. Following the surgery,
      she continued to have high-end inspiratory pressure and progressed to the chronic
      phase of adult respiratory distress syndrome (ARDS). We treated her with low-dose
      steroid therapy and she improved gradually. The patient was weaned off mechanical
      ventilation and was discharged approximately 25 weeks after LDLT. In the
      condition of cardiac or respiratory failure, cadaveric liver transplantation
      using plasmapheresis is contraindicated because of the associated high mortality
      rate. Our case suggests that if infections are controlled, a patient with
      multiple organ failure (MOF) due to end-stage liver disease might be successfully
      treated with LDLT aided by plasmapheresis and PCPS.

PMID- 15848636
TI  - Neuropsychological and neurophysiological evaluation in cirrhotic patients with
      minimal hepatic encephalopathy undergoing liver transplantation.
AB  - BACKGROUND: Cirrhotic patients without overt hepatic encephalopathy may have
      cerebral function alterations called minimal hepatic encephalopathy (MHE). Our
      goal was to evaluate the role of partial pressure of ammonia (pNH3),
      neuropsychological, and neurophysiological assessment in detecting cognitive
      changes in cirrhotic patients awaiting liver transplantation. MATERIALS AND
      METHODS: Fourteen cirrhotic patients listed for liver transplant were studied.
      All patients underwent the neuropsychological battery called PSE.
      Neurophysiological assessment including spectral EEG (sEEG), evoked potential
      P300 and pNH3 and venous and arterial ammonia levels was performed in all
      patients. Four patients were transplanted. RESULTS: Liver disease etiology was
      alcoholic in four patients, viral in six mixed in two, and cryptogenic in two.
      PSE scores revealed MHE in 8 patients; sEEG was altered in 6, and P300 in 1. No
      correlations were detected between P300, sEEG, and PSE. pNH3 and arterial ammonia
      levels were significantly higher in the subgroup of patients with altered sEEG
      and were correlated with theta band increase in sEEG but not with pathological
      PSE scores or P300 wave abnormalities. CONCLUSIONS: The combination of sEEG and
      PSE, and possibly also pNH3 and arterial ammonia, is useful in detecting cerebral
      function alterations in cirrhotic patients with no apparent encephalopathy,
      whereas P300 is not. The diagnosis of MHE obtained using the multimodal approach
      adopted in this study may enable the adequate treatment of these patients prior
      to surgery, which includes advising them not to drive and adjusting their
      priority on the waiting list for OLTx in the light of a condition that cannot be
      evaluated by Child Pugh score and MELD score.

PMID- 15848637
TI  - Surgical procedures for decompression of excessive shear stress in small-for-size
      living donor liver transplantation--new hepatic vein reconstruction.
AB  - We have reported that acute elevation of portal pressure, reflecting wall shear
      stress of sinusoidal endothelial cells, triggers liver regeneration after partial
      hepatectomy and that excessive portal hypertension induces liver failure. For
      prevention of excessive shear stress in small-for-size living donor liver
      transplantation (LDLT), we developed a new hepatic vein reconstruction to expand
      the anastomotic site. Fourteen adult patients, who underwent LDLT, were divided
      into two groups: previous end-to-end hepatic vein reconstruction in nine patients
      (group P) and the new method in five patients (group N). The outside middle and
      left hepatic veins of the graft were incised and enlarged to 40 mm. The vena cava
      was cut 40 mm longitudinally. The graft was positioned a quarter turn
      counterclockwise with the hepatic vein of the graft anastomosed end-to-side to
      the vena cava longitudinally. Postoperative portal pressures and serum total
      bilirubin levels of these two groups showed portal pressure in group N to rapidly
      decrease below 25 cm H2O following LDLT. No cases showed posttransplanted
      hyperbilirubinemia above 10 mg/dL in group N; however, all cases were small-for
      size grafts. Moreover, serum total bilirubin levels in group N were significantly
      lower than those in group P. This procedure is simple despite not using a venous
      patch. If the hepatic vein is narrow or obstructed, such as in Budd-Chiari
      syndrome, the procedure is applicable. Even in small-for-size grafts, excessive
      tension did not occurred at the portal vein or hepatic artery anastomoses.
      Moreover, it is possible to avoid outflow block and posttransplanted
      hyperbilirubinemia.

PMID- 15848638
TI  - Liver transplantation using cavoportal transposition: an effective treatment in
      patients with complete splanchnic venous thrombosis.
AB  - Complete venous thrombosis of the splanchnic system remains a major challenge in
      liver transplantation surgery. Some of these patients have been treated
      successfully by multivisceral transplantation. Cavoportal transposition is
      another alternative to treat these patients. We reviewed our single-center
      experience with this technique. Five patients with operatively confirmed complete
      splanchnic thrombosis were transplanted with the cava portal transposition
      technique. All survived the procedure; 60% survived long term. This technique is
      a useful salvage procedure in moribund patients with diffuse portal thrombosis
      who would otherwise rapidly succumb.

PMID- 15848639
TI  - The significance of hepatic vein outflow volume in hepatic outflow insufficiency
      of living right liver graft evaluated by Doppler ultrasound.
AB  - The color Doppler ultrasound has been used to evaluate hepatic vein (HV) outflow
      insufficiency based on flow velocity and waveforms. In our experience, some cases
      with flat waveforms are clinically asymptomatic. The parameters of HV flow
      velocity and waveforms are not always correlated with clinical problems. So, we
      proposed that total HV flow volume (HVFV) may be a more reliable index. From
      August 2001 to July 2003, 31 cases among 48 adult-to-adult living related
      transplants of a right liver graft had one HV anastomosis. HV velocity,
      waveforms, and HVFV were compared both before and after transplantation. We set
      the minimal HVFV ratio at 80% based on the original HVFV before graft retrieval.
      There was no significant difference in HVFV before liver graft retrieval between
      the 2 groups, but there was a significant change after transplantation. There
      were no cases of HV insufficiency among group A patients (>80%), whose HVFV
      ranged from 397 to 1181 mL/min with ratios from 75% to 180% (mean 115%). In group
      B, there were 4 complicated cases with prolonged severe ascites (<80%) with HVFV
      ratios from 56% to 76% (mean 66%). Fisher exact test showed a great significance
      (P < .001). Thus the preliminary criteria of 80% minimal HVFV ratio allows
      detection of HV insufficiency for further interventional management.

PMID- 15848640
TI  - A new venous conduit utilizing the recipient portal vein branches for segment V
      in adult partial liver transplantation.
AB  - Right anterior-medial lobe congestion due to temporary clamping of segment V
      and/or VIII is common in the operative theater during adult donor right lobe
      liver transplantation, the most common procedure in our institute. We have used
      an autogenous saphenous vein conduit to recipient portal vein tributaries in 15
      cases, as a "Y-to-I venoplasty" since January 2004. The recipient portal vein is
      transected 5 mm proximal to its bifurcation and extended to both sides with
      partial hepatic dissection. The "Y-to-I venoplasty" is made by suture closure of
      the portal vein transversely to form a tube. The average length is 7.5 cm with a
      1.3 cm width. One end of "Y-to-I venoplasty" conduit is anastomosed to the donor
      segment V branch on the back table. And the other end is anastomosed directly to
      the IVC via a new window or the middle hepatic vein stump in recipient. The phase
      distension of the conduit with respiration is noted in the operative field. A
      6/15 (40%) patency rate, was observed by CT angiography at the second
      postoperative week. All-patient conduits showed good flow on serial examinations
      at the 60th postoperative day. This new venous graft, made of recipient portal
      vein is a good conduit for segment V decongestion in adult right lobe partial
      liver transplantation.

PMID- 15848641
TI  - Liver transplantation in recipients with portal vein thrombosis: experience of a
      single transplant center.
AB  - INTRODUCTION: Although portal vein thrombosis (PVT) is no longer considered a
      contraindication for liver transplantation (OLT), it is still considered a high
      risk because of the complexity of the surgical procedure. The aim of this study
      was to evaluate the impact of PVT in the recipient during OLT on intra- and
      perioperative management and outcome. PATIENTS AND METHODS: Between April 1986
      and October 2003, 721 primary OLT included 64 patients (8.8%) with PVT. The
      underlying liver disease was postnecrotic cirrhosis in most cases (n = 37).
      Intraoperative (length of surgery, packed red blood cells (PRBC) transfusion
      requirements, ischemia time, complications) and postoperative parameters (ICU
      stay and hospitalization time, complications, actuarial graft and patient
      survival at 1 month and 1 and 5 years) were compared with a control group of
      patients submitted to OLT without PVT (n = 657). RESULTS: Portal flow was
      reestablished in 56 patients with thromboendovenectomy, in seven patients with a
      venous graft from the superior mesenteric vein, and with cavoportal
      hemitransposition in one case. The average ICU and hospital stay as well as the 1
      month and 1- and 5-year patient survivals were not significantly different in the
      PVT versus the control group. We observed slightly more PRBC transfusions and
      longer surgery procedures in the PVT group. CONCLUSIONS: Our experience suggests
      that thromboendovenectomy is the procedure of choice for PVT. The results are
      good in terms of survival rates and postoperative complications, although the
      presence of PVT may lead to more technical problems during surgery.

PMID- 15848642
TI  - Biliary reconstruction and complications of left lobe living donor liver
      transplantation.
AB  - Postoperative biliary tract complications remain one of the most serious problems
      facing patients who undergo living donor liver transplantation. The aim of this
      study was to analyze the clinical implications of three methods of biliary
      reconstruction in left lobe adult living donor liver transplantation. We
      retrospectively compared three groups of patients who underwent various biliary
      reconstructions: those who had Roux-en-Y hepaticojejunostomy (HJ) (n = 11); duct
      to duct hepaticohepaticostomy (HH) with an external stent (n = 11); or HH with T
      tube (n = 6). The median follow-up for each group was 29, 28, and 8 months,
      respectively. Bile leaks were observed in 45.5% of both the HJ and the HH with
      external stent groups. Biliary anastomotic strictures occurred in 9.1% of the
      Roux-en-Y HJ patients and in 27.2% of those who had HH with an external stent. No
      biliary complications were observed in the HH over a T-tube group (P = .049).
      Biliary reconstruction using HH with a T-tube may decrease the incidence of
      biliary complications. Despite the relatively short follow-up, these encouraging
      preliminary results warrant further studies of this biliary reconstruction
      technique for left lobe adult living donor liver transplantations.

PMID- 15848643
TI  - Transhepatic biliary catheterization before graft implant in living donor liver
      transplantation.
AB  - AIM: Despite the evolution in surgical technique, the biliary anastomosis remains
      the technical Achilles' heel of liver transplantation, especially in living donor
      liver transplantation. Interventional radiology or endoscopic procedures
      constitute the most common options to treat complications from the biliary
      anastomosis. We report a novel technique to prevent biliary complications
      following the transplant. METHODS: During the donor procedure a wire guide was
      introduced in the severed duct, left or right, in retrograde fashion. The liver
      surface was then perforated and the wire guide exposed. A 4F catheter was then
      attached to the wire guide and pulled into the bile duct passing through the end
      to-end duct-to-duct anastomosis or hepaticojejunostomy. RESULTS: This technique
      was performed in six living donor grafts: one right lobe, two left lobes, and
      three left lateral segments. All patients had no complications from the stent
      placement, biliary strictures, or leaks. One developed a hepatic artery
      thrombosis on the posttransplant day 14 with no major biliary complications.

PMID- 15848644
TI  - Role of choledochojejunostomy in liver transplantation.
AB  - AIM: This study analyzes the efficacy and rate of complications related to Roux
      en-Y choledochojejunostomy need either as the primary biliary reconstruction
      during orthotopic liver transplantation (OLT) or to treat biliary complications.
      METHODS: One hundred seventy-seven transplantation procedures were performed from
      September 1991 to December 2003 in recipients of mean age 51.9 years. Patients
      were reviewed for the type of biliary reconstruction, the prevalence of biliary
      complications, and the choice of treatment for these complications. Duct-to-duct
      anastomosis (group CDC) was performed in 153 patients (85.6%), and
      choledochojejunostomy (group CDJ) in 24 patients (14.4%). Biliary complications,
      including stenosis, bile leakage, calculosis, and extensive biliary necrosis,
      required hospitalization, surgical interventions or endoscopic approaches.
      Biliary complications in the CDC group first were addressed by endoscopic
      treatments. When endoscopic therapy failed, they were approached by surgical
      reintervention. All biliary complications in group CDJ were surgically treated,
      namely, revision of the Roux-en-Y choledochojejunostomy. The chi square test was
      used to compare frequencies, with Yates correction when necessary; P values were
      considered significant at <.05. The Mann-Whitney U test was used to evaluate
      survival. RESULTS: Fifty-eight (32.8%) biliary complications in 47 patients
      required endoscopic or surgical approaches. In group CDJ, 1 patient had bile
      leakage requiring surgical treatment. The prevalence of biliary complications was
      lower in the CDJ group than the CDC group (P < .05). Endoscopic treatment applied
      in 23 patients, failed in 11. Surgical approaches were performed in 11 patients
      after endoscopic failure, and in 13 patients as the first option to treat biliary
      complications. No failure was observed with surgical treatment. Cholangitis
      occurred in 3 patients who received surgical treatment and 4 patients who
      received endoscopic treatment. There was no statistically significant difference
      when comparing the mortality rates of the 3 types of treatment for biliary
      complications: endoscopy, surgery, and endoscopy followed by surgery. Survival
      rates were similar for the 3 types of treatment of biliary complications.
      CONCLUSION: Roux-en-Y choledochojejunostomy is a useful tool to treat biliary
      complications after OLT, especially when endoscopic treatment fails. In our
      experience, the rate of complications directly related to this technique is
      significantly lower than common duct anestomosis, whether used for biliary
      reconstruction during OLT or for posttransplantation biliary complications.

PMID- 15848645
TI  - Cost/efficacy clinical trial about the use of T-tube in cadaveric donor liver
      transplant: preliminary results.
AB  - Biliary reconstruction is the most common cause of morbidity associated with
      orthotopic liver transplantation. Our objective was to assess the complications
      and hospital resources related to the use of a T-tube. MATERIAL AND METHODS:
      Among 95 liver transplants performed from October 2002 to November 2003, 84
      patients were randomized to receive a T-tube or no T-tube. We analyzed all
      patients with a follow-up of at least of 3 months. RESULTS: Fifty-five
      transplants were analyzed with 8 months mean follow-up, including twenty eight
      with T-tube and twenty seven without a T-tube. No patient died during the follow
      up. The overall rate of biliary complications was 45.4% (25/55) including 21/28
      (75%) in the T-tube group and 4/27(14.8%) in the non-T-tube group (P < .0001).
      Complications related to T-tube extraction occurred in 48.2% (13/27), including 3
      cholangitis and 10 leaks. The costs of hospital resources due to radiological
      studies were 5329 capital JE, Ukrainian for the T-tube group vs 5785 capital JE,
      Ukrainian for the non-T-tube group. The costs of hospital resources due to
      treatment were 28,280 capital JE, Ukrainian for the T-tube group vs 10,088
      capital JE, Ukrainian for the non-T-tube group. CONCLUSIONS: Use of a T-tube
      during orthotopic liver transplantation does not seem justified. Biliary
      anastomosis stenting is followed by an increased incidence of complications, most
      of which are related to its use. Hospital stay, radiological studies, and cost of
      hospital resources are higher among the T-tube patients. Therefore its systematic
      use is not advisable.

PMID- 15848646
TI  - Efficacy of auxiliary partial orthotopic liver transplantation for cure of
      hemophilia in a canine hemophilia A model.
AB  - Metabolic liver disease can be cured by orthotopic liver transplantation. Some
      successful cases of whole or partial liver transplantation have been reported.
      Because liver function in these recipients is normal save for the production of
      the responsive metabolic factor, auxiliary partial orthotopic liver
      transplantation (APOLT) may produce a benefit. However, no experimental model of
      APOLT for metabolic liver diseases has been reported. We established a canine
      APOLT model to evaluate the clinical feasibility and efficacy of APOLT to cure
      hemophilia. The donor normal beagle dog was used to establish an APOLT model. A
      left lobe partial liver graft taken from the donor was orthotopically
      transplanted to the recipient after resection of the native left lobe preserving
      the native right lobe. Recipients showed no atrophy and comparable blood flow in
      both the graft and the native liver at the time of exploration after APOLT. Thus,
      APOLT was performed from a normal donor to a recipient with hemophilia A. In this
      recipient, blood factor VIII activity markedly increased after APOLT and was
      maintained for 7 weeks. No episode of bleeding was seen during the observation.
      In conclusion, a canine APOLT model was successfully established as evidenced by
      sustained production of factor VIII in a hemophilia recipient. These findings
      suggest the clinical feasibility and efficacy of APOLT for metabolic liver
      diseases.

PMID- 15848647
TI  - Liver transplantation for children: Red Cross Children's Hospital experience.
AB  - BACKGROUND: The liver transplant program for infants and children at the Red
      Cross Children's Memorial Hospital is the only established pediatric service in
      sub-Saharan Africa. Since 1985, 250 infants and children have been assessed and
      155 accepted for transplantation. METHODS: Since 1987, 76 children (range 6
      months to 14 years) have had 79 liver transplants, with biliary atresia being the
      most frequent diagnosis. The indications for transplantation include biliary
      atresia (n = 44), metabolic (n = 7), fulminant hepatic failure (n = 10), redo
      transplants (n = 3), and other (n = 15). Three combined liver/kidney transplants
      have been performed. Forty-nine were reduced-size transplants with donor:
      recipient weight ratios ranging from 2:1 to 11:1, and 29 children weighed < 10
      kg. RESULTS: Fifty-six (74%) patients survived 3 months to 12 years
      posttransplant. Cumulative 1- and 5-year patient survival data are 79% and 70%,
      respectively. However, with the introduction of prophylactic intravenous
      gancyclovir and the exclusion of hepatitis B virus (HBV) IgG core Ab-positive
      donors, the projected 5-year pediatric survival has been >80%. Early (<1 month)
      post-liver-transplant mortality was low, but included: primary malfunction (n =
      1); inferior vena cava thrombosis (n = 1); bleeding esophageal ulcer (n = 1); and
      sepsis (n = 1). Late morbidity and mortality was mainly due to infections: de
      novo hepatitis B (5 patients, 2 deaths); Epstein-Barr virus (EBV)-related
      posttransplantation lymphoproliferative disease (12 patients, 7 deaths); and
      cytomegalovirus disease (10 patients, 5 deaths). Tuberculosis (TB) treatment in
      three patients was complicated by chronic rejection (n = 1) and TB drug-induced
      subfulminant liver failure (n = 1). CONCLUSIONS: Despite limited resources, a
      successful pediatric program has been established with good patient and graft
      survival figures and excellent quality of life. Shortage of donors due to HBV and
      human immunodeficiency virus (HIV) leads to significant waiting list mortality
      and infrequent transplantation.

PMID- 15848648
TI  - Portal vein complications in the long-term course after pediatric living donor
      liver transplantation.
AB  - The frequency and the outcome of patients with portal vein (PV) complications in
      the long-term course after pediatric living donor liver transplantation (LDLT)
      have rarely been reported. Between June 1990 and September 2003, 527 pediatric
      patients underwent primary LDLT with left lobe grafts, among which 479 patients
      with functioning grafts at 3 months after LDLT were included in this analysis.
      The ages ranged from 29 days to 17 years, 3 months (median: 1 year, 9 months) and
      body weight from 3.1 kg to 62.4 kg (median: 9.6 kg). Biliary cirrhosis was the
      most common cause for LDLT (81%). The PV was anastomosed with or without a vein
      graft. Thirty-nine patients (8%) showed a PV complication (stenosis: 16;
      obstruction: 17; thrombus: 2; twist: 3). Their ages ranged from 4 months to 17
      years, 3 months (median: 1 year) and their body weight from 3.8 kg to 44.8 kg
      (median: 8.5 kg) at operation. PV complications were detected between 4 and 116
      months (median: 14 months) after the transplant. Splenomegaly and decreased
      platelet counts were observed in more than 90% of the patients with a PV
      complication. In 27 patients (71%), interventional venoplasty was successful.
      Eleven patients had obstruction of the PV (2.3%) including three who showed
      cirrhosis; one with severe pulmonary hypertension; one death after
      retransplantation; and one alive after retransplantation. Moderate fibrosis was
      found in two patients at 3 and 2 years after the procedure, one of whom had the
      complication of a moderate intrapulmonary shunt. Early detection of PV stenosis
      with these two markers can lead to successful angioplasty and avoid graft loss.

PMID- 15848649
TI  - Early portal vein thrombosis after pediatric split liver transplantation with
      left lateral segment graft.
AB  - Early portal vein thrombosis (PVT) represents a serious complication after liver
      transplantation (OLTx). From October 1997 through July 2004, 260 OLTx were
      performed in 231 children, including 189 of left lateral segments (LLS). We
      retrospectively analyzed the incidence and the outcome of early PVT in this
      group. A daily doppler US scan was performed during the first week after
      transplantation. Early PVT occurred in 14 patients (8%), 10 males and four
      females of median age 0.77 years. The main indication for primary transplantation
      was biliary atresia (10), followed by Byler's disease (2), acute liver failure on
      cryptogenetic cirrhosis (1), and Alagille syndrome (1). Four children underwent
      retransplantation; three cases of thrombectomy and revision of the anastomosis,
      two children were treated with beta blockers, one of whom had a later failed
      attempt at percutaneous revascularization and eventually a meso-caval shunt. Five
      patients were followed with observation and no treatment. Among the four patients
      who died, three were in the retransplantation group and one in the thrombectomy
      and revision of the anastomosis group; the overall mortality was 28%. With a
      median follow up of 399 days, 10 patients are alive with an actuarial survival at
      1 and 5 years of 72%, and graft survival rates at 1 and 5 years of 64%. PVT
      represents a serious complication after pediatric OLTx with LLS grafts. Prompt
      detection and aggressive surgical treatment in selected cases are required to
      reduce the mortality and graft loss.

PMID- 15848650
TI  - Liver transplantation in children weighting less than 6 kg: the Bergamo
      experience.
AB  - Liver transplantation (OLT) remains a major medical and surgical challenge in
      small patients. From October 1997 through July 2004, 17 babies less than 6 kg
      underwent 18 OLTs. Median age and weight were 3 months (range = 1 to 9) and 4.7
      kg (range = 2.2 to 5.8). Two whole, one reduced, and 15 split-liver grafts (left
      lateral segments) were obtained from donors of median age and weight of 11.6
      years (range = 0.5 to 62) and 50 kg (range = 7 to 63). Donor-to-recipient median
      weight ratio (D/R) was 9.1 kg (range = 1.3 to 17.6) and median graft-to-recipient
      weight ratio (GRWR) was 5% (range = 3.1 to 10). The incidence of biliary
      complications was 23%. The only vascular complication was a portal vein
      thrombosis (6%). Fourteen patients (79%) are alive with good graft function at a
      median follow-up of 39 months (range = 0.5 to 74). Three patients (all status 1)
      died on postoperative day 285 (brain death), 17 (multiorgan failure), and 229
      (cardiovascular failure during retransplantation). Actuarial patient survivals at
      6 months and 6 years are 94% and 78% while graft survivals are 89% and 74%,
      respectively. Currently all the patients listed as UNOS status 2 and 3 (73%) at
      the time of transplant are alive. During the same period one premature neonate
      (1.8 kg) who presented with fulminant hepatic failure died on the waiting list
      after 12 days. Our data confirm that the extensive use of a split-liver technique
      from small adult or pediatric cadaveric donors can offer the benefits of liver
      transplantation to small pediatric candidates with excellent results.

PMID- 15848651
TI  - Transplantation for acute liver failure in children.
AB  - We reviewed the clinical data of 30 children-hospitalized for acute liver failure
      in the last 6 years. Ten patients were not listed for liver transplantation OLTX.
      Their clinical conditions gradually improved and they are all alive without
      deficit. Among 20 patients listed, 15 underwent urgent OLTX. Two children died on
      the waiting list and three were suspended from waiting list after few days
      because of improvement. Survival according to age class was analyzed dividing the
      patients into two groups: A, age 1 year or less versus B, age between 1 and 16
      years. The patient survival was 86% at 6 months and 61% both at 1 and 2 years.
      Survival at 6 months and 1 and 2 years was 88%, 67%, and 45% for the patients in
      group A and 83%, 83%, and 83% for the patients in group B (P = NS). Observing
      graft-to-recipient weight ratio and donor-to-recipient weight ratio most patients
      received an optimal sized graft. The split-liver technique is considered the
      preferred method of liver transplantation even in the pediatric patients with
      acute liver failure; especially in the setting of a cooperative system in which
      all livers that are suitable for split-liver transplantation are shared between
      centers. In order to have the best chance for survival, children with acute liver
      failure should be referred as soon as possible to an highly specialized pediatric
      liver transplantation center that can offer all the treatment modalities that are
      currently available.

PMID- 15848652
TI  - Orthotopic liver transplantation for Byler's disease.
AB  - In this study we analyzed the features of 12 patients who underwent liver
      transplantation for progressive familial intrahepatic cholestasis (Byler's
      disease [BD]) in view of the technical features of the OLTx, incidence and type
      of complications, need for retransplantation, as well as patient and graft
      survivals. BD was the indication in 12 patients of median age 1.32 years and
      median weight 10 kg. Median follow-up was 670 days. Major surgical complications
      requiring reintervention occurred in three patients. No thrombosis of the hepatic
      artery was observed. Infections with positive blood cultures were diagnosed in
      four patients. One patient had a biliary anastomotic stenosis successfully
      treated by percutaneous techniques. Four patients had episodes of acute rejection
      treated with steroids. Two patients were retransplanted, both of whom died in the
      early postoperative period due to hepatic vein thrombosis and venoenteric
      fistula. The actuarial patient and graft survival was 83% at 1 year and 83% at 5
      years. Split-liver grafts represent an excellent organ supply for these patients,
      achieving good results with no mortality on the waiting list.

PMID- 15848653
TI  - Daclizumab induction therapy associated with tacrolimus-MMF has better outcome
      compared with tacrolimus-MMF alone in pediatric living donor liver
      transplantation.
AB  - AIMS: Immunosuppression therapy for the control of immunologic rejection is a key
      aspect in liver transplantation. The objective of this study was to evaluate
      induction therapy with daclizumab (DAC) in living donor liver transplantation
      (LDLT) in children. METHODS: We compared 2 different immunosuppression protocols
      in 30 children undergoing LDLT. The patients were divided into 2 groups: 12
      patients received tacrolimus with mycophenolate mofetil (TAC-MMF), and 18
      patients received tacrolimus with MMF and DAC induction therapy at days 0 and 14
      after LDLT (DAC-TAC-MMF). Both groups were similar with regard to age, sex,
      weight, and indication for liver transplantation. The incidence of biopsy-proved
      rejection episodes, posttransplantation lymphoproliferative disease (PTLD), and
      renal dysfunction were evaluated. Tacrolimus levels at posttransplantation day 14
      and at 2 months after transplantation were compared in the 2 groups. RESULTS:
      Acute rejection episodes were observed in 8 patients in the TAC-MMF group (66%),
      and none in the DAC-TAC-MMF group (0%; P < .05). Neither PTLD nor renal
      dysfunction was seen in any patient. Mean Tacrolimus level on posttransplantation
      day 14 was 10.67 +/- 5.4 ng/mL in the TAC-MMF group and 5.65 +/- 3.6 ng/mL in the
      DAC-TAC-MMF group (P < .05). After the second month the mean tacrolimus levels
      were 7.2 +/- 2.9 ng/mL and 6.8 +/- 3.5 ng/mL in the TAC-MMF and DAC-TAC-MMF
      groups, respectively. (P = NS). CONCLUSION: Induction therapy with DAC is safe
      and associated with a lower incidence of rejection episodes among children
      undergoing LDLT.

PMID- 15848654
TI  - Orthotopic liver transplantation for biliary atresia.
AB  - Biliary atresia (BA) represents the most frequent indication for liver
      transplantation (OLTX) in the pediatric population. The aim of this paper was to
      present a series collected over the last 7 years from October 1997 through July
      2004, including 260 pediatric OLTX in 231 patients. BA was the indication in 137
      patients. There were 69 boys and 68 girls of mean weight 10.68 kg and median age
      0.9 years. As a primary transplant, 99 patients received a LLS graft; 27 a whole
      graft; four a I+IV-VIII segment, and two a I-IV segment. Mean follow up was 1047
      days (range, 1-2496 day). Infections were diagnosed in 45 patients, vascular
      complications in 27 patients. Surgical complications that required reintervention
      occurred in 25 patients. In 41 cases biliary complications occurred, 11 requiring
      reintervention. 16 patients were retransplanted. In two cases another re-OLTx was
      performed. Currently 126 patients are alive, showing an actuarial 1 year survival
      of 92% and 5 year 91%, with actuarial graft survivals of 85% at 1 year and 82% at
      3 and 5 years. Our results confirm the effectiveness of OLTx for the treatment of
      children with BA and a failed Kasai procedure. Split liver grafts represent an
      excellent organ supply for these patients, achieving optimal results with no
      mortality on the waiting list.

PMID- 15848655
TI  - Risk factors predicting survival of liver transplantation.
AB  - Prognostic models were developed for analyzing graft survival in a single-center
      study consisting of all 388 adult liver transplantations performed during 20
      years. Proportional hazard models and generalized linear models were used to
      assess which risk factors, related to donor and recipient characteristics as well
      as graft preservation and operation, had an effect on graft survival. The
      prognostic modeling evidenced favorable trends in graft survival time during the
      successive quinquennials 1982-1987, 1988-1992, and 1993-1997, in comparison to
      the referent time period 1998-2002. Significant predictors of graft survival time
      were donor's age, recipient-donor gender compatibility, recipient's blood group,
      intraoperative blood transfusion, size of the transplanted organ, and indication
      for transplantation. Conventional histocompatibility matching did not correlate
      with graft outcome.

PMID- 15848656
TI  - Liver retransplantation: a single-center outcome and financial analysis.
AB  - Retransplantation of the liver (re-OLTx) accounts for approximately 10% of all
      liver transplants in the United States. The decision to offer a patient a second
      liver transplant has significant financial, ethical, and outcome implications.
      This large, single-center experience describes some outcome and financial data to
      consider when making this decision. One thousand three liver transplants were
      performed in 921 patients at our center. Patients were divided into adult and
      pediatric groups, and further by whether they received a single transplant or
      more than one. Overall survival, variation in survival by timing of re-OLTx, and
      survival in adults with hepatitis C were investigated, as were hospital charges
      and cost of re-OLTx. Adults, but not children, had a significant decrement in
      survival following a second transplant. Second transplants more than double the
      cost of the initial transplant, but there is a significantly higher cost
      associated with early retransplantation compared to the cost associated with late
      retransplantation (costs of first and second transplants included in both cases).
      This difference is due to a longer length of stay and associated cost in the ICU.
      Adult patients retransplanted early have the same overall survival compared to
      those done late. The sample size of the adult HCV re-OLTx population was too
      small to reach statistical significance despite their observed poorer outcome.

PMID- 15848657
TI  - Use of extended right grafts from in situ split livers in adult liver
      transplantation: a comparison with whole-liver transplants.
AB  - INTRODUCTION: We report our experience of in situ split-liver transplantation
      (SLT) for adult patients and compare the results with those achieved with whole
      liver transplantation (WLT). METHOD: From November 1997 to December 2003, 109
      liver transplantation were performed in 104 adult patients including 90 WLT (83%)
      and 19 SLT (17%) grafts. Fifteen extended right grafts (ERG, segments I + IV to
      VIII) were obtained with in situ split-liver procedures, generating also left
      lateral segment grafts, which were transplanted at our institution or elsewhere.
      Four left lobe (LL, segments I to IV) and right lobe (segments V to VIII) grafts
      were obtained by a modified in situ procedure for adult recipients. UNOS status,
      percentage of primary or secondary transplantation, and underlying liver disease
      were similar among patients receiving whole versus split grafts. Donors were
      older in whole than ERG cohorts (53 vs 26 years, P < .001). Procurement
      parameters and intraoperative profiles of transplant procedure were comparable
      among the groups. RESULTS: Median follow-up was 18 months (range: 1 to 73). Four
      patients with whole (4%) and no patient with ERG underwent retransplantation (P =
      NS). One- and 3-year patient survivals were 86% and 79% with WLT versus 93% and
      93% with ERG (P = NS). One- and 3-year graft survivals were 84% and 75% with WLT
      versus 93%, and 93% with ERG (P = NS). Incidence of vascular complications was 8%
      with WLT, 13% with ERG (P = NS). The incidence of biliary complications was 13%
      in WLT, 27% in ERG (P = NS). CONCLUSIONS: The use of ERG from in situ split
      livers for adult transplantation allowed us to obtain results comparable or even
      better than those obtained with WLT. Split-liver transplantation is an effective,
      safe mechanism to expand the cadaveric donor pool.

PMID- 15848658
TI  - Right hemiliver transplant: results from living and cadaveric donors.
AB  - Although right hemiliver transplant from living donors (LD) is gaining acceptance
      as a way to overcome the critical organ shortage, splitting a liver for two
      adults from cadaveric donor (CD) is still controversial. METHODS: From May 1999
      to August 2004 we performed nine right hemiliver transplants using segments 5-6-7
      8 from CD and 18 from LD. RESULTS: We compared the two procedures to evaluate
      both the technical aspects and the patients' outcomes. In the CD group, three
      recipients died (33%), two of whom were UNOS Status 2A. Patient and graft
      survivals were 67% (median follow-up: 23 months). Among the LD group, three
      recipients died (17%) and two were retransplanted; one because of arterial
      thrombosis and the other as a consequence of small-for-size syndrome. Patient and
      graft survivals were 83% and 72%, respectively (median follow-up: 8 months).
      There were five early complications in the CD group (55%) and five (27%) in the
      LD group. Two patients in the LD group experienced a late stenosis of the biliary
      anastomosis. DISCUSSION: Data from our early experience show that better results
      are achieved by right hemiliver transplants from LD; the morbidity and mortality
      are higher among the CD group. We believe that this finding is probably a
      consequence of better preoperative donor evaluation, shorter ischemia time,
      better logistics, and learning curve. Recipient selection is crucial; this kind
      of graft is at high risk of poor function, technical complications, and
      infections. Further experience will help to clarify the reliability of right
      hemiliver transplants from CD.

PMID- 15848659
TI  - Long-term outcome of right split in situ grafts in adults.
AB  - In situ split liver transplants represent a technical progression from ex situ
      split procedures conceived to retrieve grafts for pediatric recipients. The
      transection line runs along the falciform ligament, so the main artery to the
      right graft is the right proper artery, whereas the left graft retains the main
      arterial axis with the celiac trunk. Although the major advantages are for
      pediatric recipients, due to the expanded pool of grafts available, for adult
      recipients the results of right split in situ grafts must be compared with whole
      grafts. We considered two groups of consecutive grafts transplanted since 1993 as
      first grafts: 20 of the former and 261 of the latter. Groups were comparable for
      donor gender, recipient age and gender, perfusion solution, ischemia time, and
      follow-up time, but not for donor age and for the number of arterial anastomoses.
      Although there were more major surgical complications in the former compared with
      the latter group (40% vs 25%), the only statistically significant difference was
      found in retransplantation rate for arterial complications (15% vs 2.2%). No
      statistical difference was observed in graft or patient actuarial survival rates
      at 1, 3, or 6 years after transplantation; for right split grafts these were 85%,
      69%, and 69% and 95%, 79%, and 79%, respectively.

PMID- 15848660
TI  - Orthotopic liver transplantation for alagille syndrome.
AB  - Alagille syndrome (AS) is a dominantly inherited, multisystem disorder involving
      the liver, heart, eyes, face, and skeleton. From October 1997 through July 2004,
      260 pediatric orthotopic liver transplantations (OLTx) were performed in 231
      patients. This report describes 21 patients of median age 1.95 years (range, 0.7
      16.7) who had alagille syndrome. We present the technical features of the OLTx,
      incidence and type of complications, medical conditions related to the syndrome,
      need for retransplantation, as well as patient and graft survival rates. A split
      liver technique was used in 16 patients (76%) who received a left lateral segment
      (LLS) graft whereas 7 patients (33%) received a whole liver. Only cadaveric
      donors were used. The major surgical complications requiring reintervention in 11
      patients (52%) included biliary problems (19%) and vascular complications (17%).
      One case of hepatic artery thrombosis required retransplantation. Three
      recipients (14%) died. All other patients are alive with an actuarial survival
      rate of 90% at 1 year and 80% at 5 years. The actuarial graft survival rate is
      85% at 1 year and 75% at 5 years. Patients with AS, despite the associated
      cardiovascular anomalies, can be treated successfully by a combined approach
      between cardiologist, radiologist, cardiothoracic, and liver transplant surgeons.
      With careful planning and operative management, the results are comparable with
      those obtained with other more common cholestatic diseases.

PMID- 15848661
TI  - Living donor liver transplantation for hepatocellular carcinoma: a special
      reference to a preoperative des-gamma-carboxy prothrombin value.
AB  - BACKGROUND: Des-gamma-carboxy prothrombin (DCP) is a sensitive marker related to
      vascular invasion of hepatocellular carcinoma (HCC). The aim of this study was to
      clarify the risk factors of HCC recurrence in living donor liver transplantation
      (LDLT) with special reference to preoperative DCP values. METHODS: Forty
      consecutive adult HCC patients who underwent LDLT were examined for a correlation
      between the DCP value and vascular invasion. Risk factors for recurrence were
      also investigated using clinicopathological variables including preoperative DCP
      levels. RESULTS: The incidence of positive histological vascular invasion in
      patients with DCP values above 300 mAU/mL was higher than that with those with
      DCP value below 300 mAU/mL. Other significant risk factors for recurrence were
      over 5 cm tumor diameter, not meeting the Milan criteria, AFP value >400 ng/mL,
      histological vascular invasion, poorly differentiated histology, and male gender.
      Among the patients who did not meet the Milan criteria, those with both no more
      than 5 cm of tumor diameter and no more than 300 mAU/mL DCP exhibited a good
      prognosis. CONCLUSIONS: A high DCP value, namely >300 mAU/mL correlated with
      histological vascular invasion and was one of the strongest prognostic variables.
      Therefore, special attention should be paid to HCC patients with high DCP values.
      No correlation between the number of tumor nodules and recurrence was found;
      therefore, the Milan criteria may require revision regarding the number of tumor
      nodules.

PMID- 15848662
TI  - Liver transplantation using livers from septuagenarian and octogenarian donors:
      an underused strategy to reduce mortality on the waiting list.
AB  - Shortage of liver grafts is the only limiting factor for application of liver
      transplantation and causes an increasing mortality on the waiting list. Very old
      donors (>70 to 80 years old) are rarely referred to transplant centers because of
      the assumption that these livers will not work properly. Alternatively,
      transplant teams may be reluctant to use these very old livers due to the risk of
      poor posttransplant outcome. We reviewed our experience with seven liver
      transplantations using very old donor livers. We found that the results in terms
      of graft function and patient survival are adequate. Interestingly, the majority
      of these donors originated from a single referring donor unit (of more than 20
      units who belong to our donor network) that systematically refers all brain-dead
      donors to the transplant center, independent of the age of the potential donor.
      This implies that many of these donors are left undetected in other units. In
      conclusion, very old donors should be referred to transplant centers since
      results of transplantation with these grafts are favorable.

PMID- 15848663
TI  - Does the liver ever age? Results of liver transplantation with donors above 80
      years of age.
AB  - INTRODUCTION: Facing an increasing shortage of donor organs, donor criteria
      become more extended and so-called marginal organs are accepted for
      transplantation. For liver donation donor age above 70 years is accepted as a
      risk factor concerning primary dysfunction or nonfunction. Therefore, the aim of
      this study was to compare the early outcome of grafts older versus younger than
      80 years of age. PATIENTS AND METHOD: Between August 2002 and February 2004, 40
      adult liver transplants were performed using triple immunosuppression with
      tacrolimus, MMF, and low-dose corticosteroids. Recipients with HCC received low
      dose rapamycin after postoperative day 14. The outcome of grafts from donors
      under 80 years of age (n=35) was compared with those from donors 80 years old or
      more (n=5). For statistical analysis Mann-Whitney-U-Test and Fisher's Exact Test
      were used with P < .05 considered statistically significant. RESULTS: The average
      donor age of our population was 54.4 +/- 17.3 years with five donors older than
      80 years (80-83 years). These donors all had additional risk factors. The
      recipients of the latter grafts suffered from HCC and liver cirrhosis Child A
      (n=2) or from viral hepatitis (n=3). One recipient had advanced cirrhosis with
      severe complications. The outcomes of both groups were comparable concerning
      intraoperative and postoperative courses. All recipients of old liver grafts left
      the hospital with stable graft function. CONCLUSION: Liver grafts over 80 years
      can be transplanted with good results, especially if given to recipients with
      malignancy and otherwise stable liver function.

PMID- 15848664
TI  - Adult liver transplantation using liver grafts from donors over 70 years of age.
AB  - The increasing organ shortage calls for widening the selection criteria for liver
      transplant donors. However, concern exists about the use of grafts from donors
      older than 70 years. We report our clinical experience with graft-age related
      outcomes, presenting data on 41 patients transplanted with grafts from older
      donors. PATIENTS/METHODS: Between January 1995 and October 2003, 41 liver grafts
      were transplanted from donors older than 70 years. We analyzed patient and graft
      survival, incidence of retransplantation, initial nonfunction (INF), rejection,
      intra- and postoperative requirement for red blood cells. We also recorded
      cholestasis, protein synthesis and urinary retention. RESULTS: The mean donor age
      was 73.4 +/- 0.37 years. After one year, the patient survival was 91% and the
      graft survival 86%. The retransplantation rate was 9.75%; only one graft was lost
      due to INF. We observed an incidence of 11 rejection episodes. Of these, five
      patients needed OKT3 therapy for steroid-resistent rejection. The intra- and
      postoperative requirement for red blood cells was 4.0 +/- 0.65 and 1.4 +/- 0.25
      units. Cholestasis, protein synthesis, and urinary retention parameters were
      within normal limits. CONCLUSIONS: Among donors of mean age 73.4 years, patient
      and graft survivals were excellent. One organ was lost due to INF. The intra- and
      postoperative need for red blood cells was within acceptable ranges. Liver
      function tests, cholestasis, and retention parameters were normal after 1 year
      follow up. Thus, we recommend to accept liver grafts from donors older than 70
      years to expand the organ pool.

PMID- 15848665
TI  - Livers transplanted from donors after cardiac death occurring in the ICU or the
      operating room have excellent outcomes.
AB  - BACKGROUND: Increasing donor hospital cooperation with donation after cardiac
      death (DCD) requires the organ procurement organization (OPO) to use current
      withdrawal of life support (WLS) protocols. Hospital ICU nurses/physicians are
      comfortable performing the emotionally draining procedure of WLS in the ICU while
      OPOs are reluctant to accept these donors due to increased warm ischemia (WI). In
      our area, several hospitals will only allow WLS to occur in the ICU. This study
      compares liver outcomes from DCD donors where death occurred in the ICU (DCDICU)
      vs the OR (DCDOR). METHODS: From March 2003 to June 2004, 34 DCD donors were
      recovered by our OPO. WLS occurred in the ICU for 26 donors (76%) and in the OR
      for 8 donors (24%). Thirteen of 26 DCDICU and 5 of 8 DCDOR livers were
      transplanted. Donor demographics, warm ischemic time, cold ischemic time,
      distance shipped, and recipient functions were analyzed. RESULTS: Eighteen livers
      were transplanted both locally and at distant transplant centers. Results are
      outlined in the . CONCLUSIONS: Although DCDICU donors averaged approximately 4
      minutes longer WI than DCDOR donors, short-term results for both groups were
      equivalent. These findings support using DCDICU livers. DCDICU donors have the
      potential to significantly improve donor hospital cooperation.

PMID- 15848666
TI  - Decrease of CD4+CD25+ T cells in peripheral blood after liver transplantation:
      association with immunosuppression.
AB  - CD25 (IL-2 receptor alpha-chain) marks a population of CD4-positive T cells with
      a suppressor phenotype. These CD4+CD25+ regulatory T cells can suppress both
      effector T cells and antigen-presenting cells and have been identified as a
      principle regulator of tolerance in experimental transplantation models. In the
      setting of human liver transplantation, however, little is known about the
      dynamics of these cells in relation to rejection, tolerance, and
      immunosuppression. In the current study we determined CD4+CD25+ T cell in blood
      of liver transplant recipients using flow cytometry and investigated a possible
      link with immunosuppressive therapies. Peripheral blood mononuclear cells (PBMC)
      of 27 liver transplant patients (pretransplantation and 12 months
      posttransplantation) and 16 healthy controls were included. We found that the
      percentages of CD25+ cells within the CD4 T-cell population was significantly
      reduced in more than two-thirds of patients 1 year after transplantation. Also
      the total percentage of CD4-positive T cells declined significantly within this
      period, making the absolute reduction of regulatory T cells after transplantation
      even more profound. Comparing PBMC samples of patients and healthy controls
      revealed an increased percentage of CD4+ T cells in the patients before
      transplantation, probably related to the chronic liver illness. The reduction in
      CD4+CD25+ T cells after transplantation was similar for different
      immunosuppression regiments. All patients, however, received calcineurin
      inhibitors, suggesting a possible suppressive effect of this therapy on
      regulatory T-cell levels in peripheral blood. Currently, assays for regulatory T
      cell activity are used to further support this hypothesis.

PMID- 15848667
TI  - Pregnancy and delivery after liver transplantation.
AB  - AIM: According to statistics, women constitute one-third of all liver recipients
      and approximately 75% of female recipients are of reproductive age. Successful
      liver transplantation in these patients results in the restoration of menstrual
      function and fertility. The aim of this study was to assess the course of
      pregnancy and delivery in liver-transplanted women. MATERIALS AND METHODS: We
      retrospectively analyzed data of 138 liver-transplanted women, aged from 18 to 63
      years, who underwent regular gynecological evaluations. Among 77 patients of
      reproductive age, 11 women conceived and delivered babies. RESULTS: All patients
      have successfully delivered. The mean gestation age at delivery was 36.5 weeks.
      All neonates were delivered in a good state with no congenital abnormalities.
      Common pregnancy complications were preterm birth, anemia, intrahepatic
      cholestasis, and infection. In 1 case, graft rejection was observed due to
      willful discontinuation of immunosuppressive therapy. Two spontaneous vaginal
      deliveries and 9 caesarean sections were performed. All caesarean sections were
      performed for obstetrical indications: fetal intrauterine asphyxia (n = 4),
      breech presentation (n = 2), threatening intrauterine infection (n = 2), and
      preterm twin delivery (n = 1). CONCLUSION: High-risk pregnancies in liver
      transplanted women are generally associated with good outcomes, although an
      increased rate of preterm labor, intrauterine infections, anemia, and cholestasis
      were observed. Pregnancy did not seem to impair graft function or accelerate
      rejection in patients receiving immunosuppressive therapy.

PMID- 15848668
TI  - Experience of a successful pediatric liver transplant program in Mexico.
AB  - Orthotopic liver transplantation (OLT) has been very difficult to develop in
      Mexico and for many years its occurrence was anecdotal. This report presents the
      results of a pediatric liver transplant program, analyzing the variables that
      affect outcomes. Between June 1998 and March 2004, 35 OLT were performed in 34
      recipients including 80% cadaveric whole-organ grafts and 20% segmental grafts,
      with 11% from cadaveric and 9% from living donors. Most of the recipients were
      infants or toddlers weighing less than 15 kg. There was only 1 case of arterial
      thrombosis (2.8%); the graft was saved with a Kasai procedure. Biliary
      complications were present in 22% of cases, all resolved with reoperations.
      Posttransplant cytomegalovirus infection or reactivation (28%), acute rejection
      (25%), or posttransplant lymphoproliferative disorders (5.7%) were not a cause of
      graft or patient loss. Overall, 1- and 5-year patient survival rates are 77.1%
      and 74.2%, respectively; however, when the 1998-2000 cohort was compared with the
      2001-2004 cohort, there was a significant difference in survival (P = .004). The
      1-year patient survival for the later group is 91.6%. We performed the first
      successful living donor liver transplantation and the first simultaneous liver
      kidney transplantation in a child in our country. Our results demonstrate that
      pediatric liver transplantation is a feasible undertaking in Mexico, with
      survival rates comparable to those of foreign centers.

PMID- 15848669
TI  - The impact of Campath 1H induction in adult liver allotransplantation.
AB  - BACKGROUND: We report our experience with Campath 1H in adult liver
      allotransplantation. METHODS: Between December 2001 and February 2004, 77
      patients underwent liver transplantation using Campath 1H induction and low-dose
      maintenance tacrolimus immunosuppression. The control group consisted of 50
      patients with similar baseline characteristics and the same eligibility criteria,
      transplanted under our standard Tacrolimus/steroids regimen. Hepatitis C patients
      were excluded from the study. RESULTS: Patient and graft survival were similar
      for both groups. The incidence of rejection was significantly lower in the
      Campath vs the control group (51% vs 65% at 12 months, P = .009). Tacrolimus
      trough levels and conversion from Tacrolimus or the addition of other
      immunosuppressive drugs due to nephrotoxicity were also significantly lower in
      the Campath 1H group. CONCLUSION: Campath 1H induction with low-dose Tacrolimus
      maintenance immunosuppression is an effective regimen in reducing acute rejection
      in adult liver transplantation, while maintaining lower tacrolimus levels and
      less nephrotoxicity than our conventional immunosuppressive regimen.

PMID- 15848670
TI  - New strategy for ABO-incompatible living donor liver transplantation with anti
      CD20 antibody (rituximab) and plasma exchange.
AB  - It is more difficult to control humoral rejection in living donor liver
      transplantations (LDLT) across the ABO blood group barrier than in matched or
      compatible combinations. We achieved excellent results in ABO-incompatible
      transplantation with novel immunosuppressive regimens and plasma exchange (PE).
      Among 82 LDLT were 10 cases of ABO-incompatible recipients, including three who
      were administered rituximab for rescue or prophylactic therapy.
      Pretransplantation PE was performed as necessary to maintain hemagglutinin titers
      below 1:16 and posttransplantation PE was performed when there were signs of
      hyperacute rejection associated with high titers. Induction immunosuppression
      consisted of FK506, steroid, mycophenolate mofetil (MMF), and rituximab. The
      first patient was administered rituximab with deoxyspergualin (DSG), steroid
      pulse therapy, and PE on postoperative day (POD) 7, because of biopsy-proven
      humoral acute rejection. The titers and LFTs improved drastically. The second and
      third patients were administered rituximab just after the operation with other
      routine immunosuppressants for prophylaxis of hyperacute rejection. The second
      patient showed a slight deterioration in LFTs with an elevated titer, which
      normalized after steroid pulse therapy and PE. The third patient had no episodes
      of rejection. At present, that is 27, 17, and 6 months after the operations
      respectively, the 3 transplant recipients are in stable condition.

PMID- 15848671
TI  - Tacrolimus for primary liver transplantation: 12 to 15 years actual follow-up
      with safety profile.
AB  - BACKGROUND: Tacrolimus has been increasingly used for liver transplantation
      during the last decade. The drug has immunological advantages in short- to medium
      term follow-up. However, data on longitudinal follow-up are lacking. AIM: The aim
      of the present report was to examine the impact of tacrolimus in primary adult
      and pediatric liver transplantation (LTx) patients. MATERIAL AND METHOD: One
      thousand consecutive primary LTx patients were performed under tacrolimus between
      August 1989 and December 1992 were followed up until August 2004. Mean follow-up
      was 13.4 +/- 0.92 (range, 11.7-15) years. There were 600 males and 400 females
      with a mean age of 42.6 +/- 20.2 years. There were 166 children (age 18 years or
      younger) and 834 adults, of whom 204 were older than 60 years (seniors). RESULTS:
      Four hundred ninety-seven (49.7%) patients died in the follow-up period. The
      overall 15-year actuarial patient survival rate was 51.4%. The survival rate for
      children was significantly better (81.3%) compared with adults (47.5%) and
      seniors (36.4%) (P = .0001). One hundred fifty-one patients received a second
      LTx, 22 patients received a third LTx, and 4 patients received a fourth LTx. Over
      all 15 years the actuarial graft survival rate was 46.1%. At last follow-up,
      69.1% of patients were off steroids. The majority of late deaths were due to age
      related complications, recurrence of disease, and De novo cancers. CONCLUSION:
      The data on longitudinal follow-up have shown actuarial survival for children to
      be significantly better than in adults and seniors. Graft loss from immunological
      causes are rare even with long-term follow-up.

PMID- 15848672
TI  - Conversion of stable liver transplant recipients from a twice-daily Prograf-based
      regimen to a once-daily modified release tacrolimus-based regimen.
AB  - INTRODUCTION: Modified release (MR) tacrolimus is an extended release formulation
      administered once daily. The purpose of this pharmacokinetic (PK) study was to
      evaluate tacrolimus exposure in stable liver transplant recipients converted from
      Prograf twice a day to MR tacrolimus once daily. METHODS: This was an open-label,
      multicenter study with a single sequence, four-period crossover design. Eligible
      patients were 18 to 65 years of age, >6 months posttransplant with stable renal
      and hepatic function and receiving stable doses of Prograf twice a day for >2
      weeks prior to enrollment. Patients received Prograf twice a day on days 1 to 14
      and 29 to 42. Patients were converted to the same milligram-for-milligram daily
      dose of MR once daily on days 15 to 28 and 43 to 56. Twenty-four-hour PK profiles
      were obtained on days 14, 28, 42, and 56. Laboratory and safety parameters were
      also evaluated. RESULTS: Of 70 patients, 62 completed all four PK profiles. The
      AUC0-24 of tacrolimus was comparable for Prograf twice a day (days 14 and 42) and
      MR tacrolimus once daily (days 28 and 56). The 90% confidence intervals for MR
      tacrolimus versus Prograf at steady state (days 28 and 56 vs days 14 and 42) was
      0.85 to 0.92 for AUC0-24. MR tacrolimus was well tolerated with a safety profile
      comparable to that of Prograf. AUC0-24 was highly correlated to Cmin for Prograf
      (day 14, r = .93; Day 42, r = .89) and for MR tacrolimus (day 28, r = .93; day
      56, r = .92). Renal and liver function remained stable. One patient experienced
      acute rejection. CONCLUSION: The steady-state tacrolimus exposure of MR
      tacrolimus once daily is equivalent to Prograf twice a day after a milligram-for
      milligram conversion in stable liver transplant recipients.

PMID- 15848673
TI  - Preliminary analysis of early outcomes of a prospective, randomized trial of
      complete steroid avoidance in liver transplantation.
AB  - Steroids are a mainstay in liver transplantation for induction and maintenance
      immunosuppression but are associated with significant adverse effects. While
      prior studies have successfully limited the use of steroids, whether complete
      steroid avoidance will improve outcomes remains unclear. To further evaluate the
      need for steroids, consenting patients who underwent liver transplantation
      between June 2002 and May 2004 were entered into a prospective, randomized trial
      to receive either standard therapy (tacrolimus, mycophenolate mofetil, steroid
      induction/maintenance) or complete steroid avoidance (standard therapy without
      steroid induction/maintenance). Clinically suspected rejection was confirmed by
      biopsy and treated with pulse steroid therapy. Outcomes were compared on an
      intention to treat basis. Of the 72 patients enrolled, 36 (50%) were randomized
      to the steroid avoidance group with a mean follow up of 412 +/- 41 days. Donor
      and recipient characteristics were similar between groups. The steroid avoidance
      group was more likely to have significant infections (52% vs 28%, P = .03). There
      was a trend toward an increased rate of acute rejection (25% vs 14%, P = .23).
      Twelve of 36 recipients (33%) enrolled in the steroid avoidance group later
      received steroids. The incidence of recurrent hepatitis C was similar between
      groups. The 1-year patient (90% vs 83%, P = .44) and graft survivals (90% vs 81%,
      P = .27) were similar between groups. These data suggest complete steroid
      avoidance in liver transplantation results in acceptable patient and graft
      survival. However, the potential long-term benefits of steroid avoidance,
      including a decrease in severity of recurrent hepatitis C, remain under
      investigation.

PMID- 15848674
TI  - Steroid-free induction and preemptive antiviral therapy for liver transplant
      recipients with hepatitis C: a preliminary report from a prospective randomized
      study.
AB  - Recurrence of hepatitis C (HepC) has been a most difficult dilemma in liver
      transplantation (OLT) because the effects of immunosuppression with steroid,
      mycophenolate mofetil (MMF) calcineurin antagonists, and anti-interleukin-2
      antibody as well as the role of preemptive antiviral therapy are uncertain. In
      this study, we randomized OLT recipients with HepC into two treatment arms:
      tacrolimus+daclizumab+MMF (study arm) versus tacrolimus+steroids+MMF (control
      arm). The study arm only received steroids for the treatment of biopsy-proven
      rejection episodes. Both arms received preemptive anti-viral therapy with Pegasys
      and ribavirin. The 39 enrolled patients (among 50 to be enrolled) have median
      follow-up of 458 days with 23 patients (8 in study arm, 15 in control arm) having
      reached 1 year. The incidences of rejection episodes within 0 to 3 months, 3 to 6
      months, and 6 to 12 months were (study vs control): 0% vs 28%; 0% vs 6%; and 13%
      vs 20%; respectively (P = NS). The 1-year protocol biopsies showed advanced
      fibrosis (stage 3 or greater) in 20% (3 of 15) of the control arm, but none (0 of
      7) of the study arm (P = NS). We compared anticipated side effects of steroids in
      the first 3 months (study vs control): hypertension (36% vs 58%, P = NS), PTDM
      (7% vs 43%, P = .02), and wound infections (14% vs 37%, P = NS). In conclusion,
      liver transplant recipients with HepC tolerate a steroid-free protocol. There was
      a trend toward reduced steroid side effects and a lower incidence of advanced
      fibrosis in 1-year biopsy samples among patients receiving the steroid-free
      protocol.

PMID- 15848675
TI  - Nephrotoxic effects of immunosuppressant therapy in pediatric liver transplant
      recipients.
AB  - Drugs used for immunosuppression have been implicated in causing numerous long
      term side effects including nephrotoxicity, glucose intolerance, and
      hyperlipidemia. In this study, we reviewed our pediatric liver transplant
      recipients in terms of glomerular filtration rate (GFR) as well as fasting
      glucose and lipid profiles. To date, 79 pediatric liver transplantations have
      been performed at our center: 24 transplantations of at least 5 months to a
      maximum of 7.3 years posttransplant are reviewed herein. The mean time
      posttransplantation was 2.1 years. Nine boys and 15 girls showed a distribution
      of 19 mixed race, 3 black, and 2 white patients. The mean age at the time of
      transplantation was 6.6 years (0.8-13.3 years) with 8 cases under the age of 3
      years. All recipients started with Cyclosporine Neoral (CSA) as first line, but,
      at the time of testing, immunosuppression included 5 children on CSA and 19 on
      Tacrolimus. Radionuclide 51 Cr-EDTA Glomerular Filtration Rates (GFR) showed a
      range from 21 to 220 mL/min/1.73 m2 (mean 96.1, median 89.8). Seven cases had a
      GFR less than 75 mL/min/1.73 m2. Twenty-one children were on antihypertensives
      agents: 15 children on 1 agent and 6 children on 2 agents. On full fasting lipid
      profiles, the total cholesterol ranged from 2 to 7.9 mmol/L (mean 4.4). Only 1
      child is currently on statin therapy. Fasting glucose ranged from 3.2 to 5.9
      mmol/L (mean 4.1) No difference was observed in glucose values between CsA and
      Tacrolimus. Thus, immunosuppressive therapies, such as the calcineurin
      inhibitors, are known to cause nephrotoxicity, which is of concern in pediatric
      liver transplant recipients. Almost all our patients currently require
      antihypertensive therapy. At present, the renal function is adequate in the
      majority of the group, but this study needs to be extended to other pediatric
      liver transplant recipients with particular emphasis on those who are more than 5
      years posttransplantation.

PMID- 15848676
TI  - Infectious complications limit the outcome of liver transplantation in medical
      urgency code 2 patients.
AB  - The Organ shortage has caused an accumulation of acutely decompensated patients
      listed as medical urgency code 2 (MUC 2) (United network for Organ Sharing 2)
      while awaiting liver transplantation. Between June 1997 and June 2003, 22 of 360
      liver transplantation patients (6%) were listed as MUC 2. Prophylactic
      immunosuppression consisted of calcineurin inhibitor-based drug therapy, using
      antithymocyte globulin or interleukin-2 receptor antagonist induction in 64%. The
      overall perioperative infection rate was 50%, and the rejection rate was 23%. We
      observed 7 episodes of oral or genital herpes simplex virus lesions; 2 patients
      (both with cytomegalovirus-mismatched transplants) developed cytomegalovirus
      disease, and another 5 patients received ganciclovir for preemptive therapy or
      prophylaxis. Two patients developed pneumonia: 5, sepsis that originated in 4
      cases from a contaminated central venous line; and 1 methicillin-resistant
      endocarditis, which resulted in Staphylococcus aureus lethal outcome. After a
      median follow up of 3 years, 1 patient underwent a repeat transplantation
      procedure and 6 patients had died, 4 of them from infectious complications. Liver
      transplantation of MUC 2-listed patients may result in acceptable results similar
      to those of MUC 3 and MUC 4 categories.

PMID- 15848677
TI  - DNA microarray-based gene expression profiles of cytomegalovirus infection and
      acute rejection in liver transplants.
AB  - An association between cytomegalovirus (CMV) infection and alloresponse has been
      suggested. CMV increases inflammation and adhesion molecule expression in graft,
      and induces cytokines and growth factors, linked with transplant vasculopathy and
      chronic rejection. We have investigated the gene expression of various
      inflammatory factors in the CMV-associated immune response and compared this with
      the immune response of acute rejection in liver transplants by using DNA
      microarray technology. Gene expression was studied at mRNA level in biopsies from
      liver transplant patients experiencing CMV infection or acute rejection. RNA
      extracted from liver grafts after reperfusion was used as control material. Among
      the strongly upregulated genes in the specimens obtained from liver transplants
      during CMV infection were IFN-gamma, caspases 1 and 3, granzymes A and B, TGF
      beta receptors II and III, IL-10 receptor alpha, VCAM-1, TNF receptor, IL-4, TNF
      alpha, IL-10, IL-2 receptor beta, IL-1beta, PDGF-receptor beta, vascular adhesion
      protein-1, TGF-beta2, and ICAM-1. In biopsies with acute liver allograft
      rejection, the most significantly upregulated genes were MHC class II, IFN-gamma,
      caspases 1 and 3, IL-2R beta and gamma, granzymes A and B, VLA-4, L-selectin, E
      selectin, VCAM-1, and IL-1beta. Upregulated genes common for CMV and alloresponse
      were granzyme A and B, E-selection, IFN-gamma, VCAM-1, VLA-4, TNF, caspases 1, 3,
      and 8, and PDGF. Microarray analysis defined different entities in the immune
      responses of CMV infection and acute rejection. The differences and similarities
      of the gene expression profiles related to those in CMV infection and rejection
      may help to understand the intragraft immunologic events.

PMID- 15848678
TI  - HHV-6-DNAemia related to CMV-DNAemia after liver transplantation.
AB  - In addition to cytomegalovirus (CMV), activation of other betaherpesviruses,
      especially human herpesvirus 6 (HHV-6), has been reported in liver transplant
      patients. The purpose of this study was to investigate the posttransplant HHV-6
      DNAemia in relation to CMV-DNAemia in liver transplant patients. Thirty-one adult
      liver allograft recipients were regularly monitored for CMV and HHV-6 during the
      first 3 months after transplantation. For the diagnosis of CMV infections, pp65
      antigenemia assay and quantitative DNA-PCR were used. HHV-6 was demonstrated by
      using quantitative DNA-PCR and HHV-6 antigenemia test. Altogether 253 blood
      specimens of 31 recipients were analyzed. In addition, CMV and HHV-6 specific
      antigens were demonstrated by immunohistochemistry in liver biopsy specimens in
      the case of graft dysfunction. Thirteen patients (40%) developed a clinically
      significant CMV infection, at a mean of 33 days (range 5 to 62 days) after
      transplantation and were treated with intravenous ganciclovir. The peak viral
      loads of these symptomatic CMV infections were high (CMV-DNA 34210 +/- 37557
      copies/mL plasma). Six additional asymptomatic patients demonstrated
      significantly lower CMV-DNAemia levels (1020 +/- 1008 copies/mL, P < .05), and
      were not treated. Concurrently with CMV, HHV-6 DNAemia and antigenemia were
      detected in 17 of 19 patients, mean 11 days (range 6 to 24 days) after
      transplantation. HHV-6 appeared prior to CMV in most cases (12 of 17). However,
      the peak viral loads were low (HHV-6-DNA <1500 copies/mL blood), even in the five
      patients who demonstrated HHV-6 antigens on liver biopsy. All CMV infections were
      successfully treated with ganciclovir and the CMV DNAemia/antigenemia subsided.
      HHV-6 also responded to the antiviral treatment, but more slowly and less
      clearly. In conclusion, HHV-6 activations were common and usually associated with
      CMV infection in liver transplant patients. Further investigation of the clinical
      significance of HHV-6 DNAemia/antigenemia is necessary.

PMID- 15848679
TI  - Interferon combined with cyclosporine treatment as an effective countermeasure
      against hepatitis C virus recurrence in liver transplant patients with end-stage
      hepatitis C virus related disease.
AB  - Hepatitis C virus (HCV) is the most common cause of end-stage liver disease in
      transplant recipients. Progression of recurrent HCV infection is accelerated.
      Cyclosporine is not only an immunosuppressive drug, but also an anti-HCV drug. We
      reported here the beneficial effect of combined interferon and cyclosporine
      treatment for chronic hepatitis C. We recommend this protocol for established HCV
      related graft disease.

PMID- 15848680
TI  - Genotypic resistance of hepatitis B virus to lamivudine in renal transplant
      recipients.
AB  - Renal recipients with hepatitis B virus (HBV) should be treated with prolonged
      lamivudine. However, lamivudine resistance usually results after YMDD mutation
      within the HBV polymerase gene. Thereupon, the aim of this study was to
      investigate the genotypic resistance to lamivudine among renal transplant
      recipients to identify its effect on the clinical course of HBV in these
      patients. Between March 1997 and September 2003, eight of 17 renal transplant
      patients with hepatitis B virus were enrolled into this study and treated with
      100 mg of lamivudine once each day. We amplified a selected region of the
      polymerase gene of HBV in order to confirm mutations in the YMDD motif. Mutations
      of YMDD region were observed in five of eight patients (62.5%). Out of five
      patients positive for HBV DNA, three (60%) showed genotypic resistance (YMDD
      mutation) with a normal ALT level. Two patients converted to HBV DNA negative.
      But, they were not associated with HBeAg seroconversion. Out of three patients
      who were pretransplant HBV DNA negative, genotypic resistance was observed in two
      patients (67%) revealing both positivity of HBe antibody and negativity of HBV
      DNA. In conclusion, although a normal ALT level and HBV DNA negative are
      maintained, the mutation of the YMDD locus may develop. Accordingly, we suggest
      that if the YMDD mutation is not involved in the progression of hepatitis B,
      lamivudine therapy should be continued despite genotypic resistance.

PMID- 15848681
TI  - Risk of transmission of hepatitis B virus from anti-HBC positive cadaveric organ
      donors: a collaborative study.
AB  - Organ donors with a serologic profile of recovered (HBsAg negative and/or anti
      HBc IgG positive) hepatitis B virus infection (HBV) have been reported to
      transmit HBV to recipients. In Italy, up until 2002, anti-HBc determination was
      not mandatory. We retrospectively evaluated the incidence of HBV transmission
      among recipients transplanted with organs from anti-HBc positive donors from 1997
      to 1999. Anti-HBc was screened in 886 available sera among 964 HBsAg and anti-HCV
      negative donors. HBV transmission was evaluated in 325 kidney, liver, and heart
      recipients according to their pretransplant HBV serum profile. Of 210 anti-HBc
      positive donors, 185 were anti-HBc positive/anti-HBs positive and 25 anti-HBc
      positive/anti-HBs negative with a prevalence of 20.8% and 2.8%, respectively. One
      hundred seven sera (51%) were collected from donors after transfusion of blood
      components, the remainder were either before transfusion or from nontransfused
      donors. The 210 anti-HBc positive subjects donated 356 kidneys, 117 livers and
      117 hearts, among whom follow-up is presently available for 251 kidney, 61 liver,
      and 25 heart recipients. No HBV transmission was observed independent of the
      recipient immunological profile among the kidney or heart recipients. In liver
      recipients, no transmission was reported in recovered or vaccinated patients,
      while a high incidence (43%) of de novo hepatitis was observed among naive
      patients. In conclusion, there does not seem to be a risk of transmitting HBV
      through anti-HBc positive transplants in heart and kidney recipients; only naive
      liver recipients are at high risk of HBV infection.

PMID- 15848682
TI  - Review of 31 cases of morphologic hepatitis in liver transplant patients not
      related to disease recurrence.
AB  - AIMS: We examined the clinical and pathologic features of morphologic hepatitis
      occurring after liver transplantation (LT) that is unrelated to disease
      recurrence. METHODS: Between February 1998 and December 2003, 704 primary LTs
      were performed at our center. Patients transplanted for diagnoses with low risk
      of disease recurrence were considered for our study (n = 282). Those with
      hepatitis C (HCV), hepatitis B (HBV), primary biliary cirrhosis (PBC), primary
      sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) were excluded. Those
      with morphologic hepatitis comprised our case series and had medical records
      reviewed for clinical associations, duration, and outcome. RESULTS: Thirty-one
      cases were identified. They were transplanted for cryptogenic cirrhosis (n = 13),
      steatohepatitis (n = 12), alpha-1-antitrypsin deficiency (n = 3), tumor (n = 2),
      and acetaminophen toxicity (n = 1); 22 cases (67%) presented within the first 8
      months post-LT (range, 0.5-72 months). Histological activity was mild in 19 and
      moderate in 12. Associated conditions were identified in 19 patients (57%) with 3
      categories being identified: probable drug toxicity (n = 7), systemic infection
      (n = 4), and mechanical or hemodynamic abnormalities (n = 8). Of the 25 cases
      that underwent follow-up biopsy 2 to 32 months (mean, 15.5 months) after the
      index biopsy, 10 cases had resolution and 15 cases had persistence of the
      infiltrate. One patient had evidence of de novo HBV infection. CONCLUSIONS:
      Morphologic hepatitis occurred in 11% of patients at low risk for disease
      recurrence. Associated conditions could be grouped into three categories: drug
      toxicity, systemic infection, and mechanical or hemodynamic factors. Most cases
      did not appear to progress or improved over time, with no allograft loss
      occurring as a result of chronic hepatitis.

PMID- 15848683
TI  - Methicillin-resistant Staphylococcus aureus infection in liver transplantation: a
      matched controlled study.
AB  - The purpose of this study was to evaluate the clinical impact of methicillin
      resistant Staphylococcus aureus (MRSA) infections on transplant recipients.
      METHODS: Liver and kidney recipients with MRSA infections were retrospectively
      identified and compared to an age, gender, UNOS status, organ transplanted, and
      transplant date matched (2:1) non-MRSA-infected recipient control group. All MRSA
      infections were initially treated with vancomycin, and four (33%) liver
      recipients were converted to linezolid therapy after failing to improve with
      vancomycin. RESULTS: The overall MRSA infection incidence was 1.4% (24/1770) with
      MRSA more common in liver (3.75%; 12/320) than kidney transplants (0.8%; 12/1450)
      (P < .001). The most common sites of MRSA infection were blood (42%), lung (38%),
      and abdomen (29%). The MRSA group had a greater percentage of prior antibiotic
      usage (79% vs 40%; P < .0015). The MRSA group experienced more posttransplant
      complications (52% vs 19%; P < .011)), and exhibited a trend toward greater
      length of stay in the intensive care unit (7.8 vs 4.6 days; P = .09), but not
      overall length of stay. Survival was similar in MRSA and non-MRSA groups (75% vs
      88%; P = .17). No significant differences in mortality were noted between liver
      and kidney recipients infected with MRSA (P = .6). CONCLUSION: MRSA infection is
      associated with a higher incidence of posttransplant complications and antibiotic
      usage in both liver and kidney recipients compared to patients with MRSA
      infection.

PMID- 15848684
TI  - Comparison between nifedipine and carvedilol in the treatment of de novo arterial
      hypertension after liver transplantation: preliminary results of a controlled
      clinical trial.
AB  - There is no controlled clinical trial on the treatment of de novo arterial
      hypertension after liver transplantation (LT) a common complication using
      calcineurin inhibitors (CNI) for immunosuppressive therapy. The aim of this study
      was to compare the efficacy and safety of nifedipine, a calcium channel blocker,
      and carvedilol, an alpha1- and beta-blocker. The study included 50 patients who
      developed arterial hypertension after LT. The data on the first 30 patients who
      have completed 12-month follow-up are reported herein. Eighteen patients received
      nifedipine, and 12 patients received carvedilol. Patients were evaluated monthly
      at the outpatient clinic for 1 year. If patients developed severe adverse effects
      to nifedipine, they were switched to carvedilol and vice versa (therapy failure).
      The two groups were similar for clinical features, indications for LT,
      immunosuppressive therapy, and baseline blood pressures. A failure of treatment
      was observed in 9 of 18 patients treated with nifedipine (50.0%) and one of 12
      patients treated with carvedilol (8%, P < .025). Nifedipine was effective in 4 of
      18 patients, carvedilol, in 4 of 12 patients (22.21% vs 33.3%, P = NS). Two of
      the nine nonresponders to nifedipine responded to carvedilol. The efficacy of
      monotherapy was observed in 11 of 40 randomized patients (27.5%). Carvedilol
      monotherapy is as effective as nifedipine but far better tolerated.

PMID- 15848685
TI  - Transjugular intrahepatic portosystemic shunts for refractory ascites after liver
      transplantation.
AB  - PURPOSE: To study the efficacy of transjugular intrahepatic portosystemic shunts
      (TIPS) in the management of refractory ascites after liver transplantation.
      PATIENTS AND METHODS: Between January 1995 and December 2003, 309 primary adult
      liver transplants were performed. Refractory ascites was defined as active
      interventions (salt restriction, diuretic use, repeated paracentesis) needed
      beyond 30 days after transplantation. These patients were managed with TIPS
      placement. RESULTS: Eight TIPS were placed in 8 patients at a mean of 11.5 months
      after transplantation (range, 2-36 months). There were 5 males and 3 females, age
      54 +/- 8.2 years. Hepatitis C was the primary diagnosis in 7 patients and primary
      biliary cirrhosis in 1. Indications for TIPS included refractory ascites (8),
      associated variceal bleeding (2), and various degrees of hepatic vein outflow
      stenosis (3). Seven patients had resolution of ascites and associated findings of
      portal hypertension, and 1 patient with persistent ascites had severe hepatic
      vein outflow stenosis and associated hepatitis C in the allograft. Two patients
      required retransplantation for recurrent hepatitis C. There were 3 deaths: liver
      failure (1), organ failure after retransplantation (1), and lung cancer 5 months
      after TIPS (1). Currently, 5 patients are alive without clinical evidence of
      ascites 9, 13, 15, 24, and 70 months after TIPS. CONCLUSIONS: The TIPS device can
      be used safely and effectively to control refractory ascites after liver
      transplantation. In the setting of organ dysfunction, these patients should be
      considered sooner for retransplantation.

PMID- 15848686
TI  - Microvascular tumor embolism: independent prognostic factor after liver
      transplantation in hepatocellular carcinoma.
AB  - Microscopic tumor cell dissemination may be a more important factor in the
      recurrence of hepatocellular carcinoma (HCC) after liver transplantation,
      probably because of posttransplant immunosuppression. The presence of
      microvascular tumor embolism was undetermined as a factor for HCC recurrence
      after orthotopic liver transplantation (OLT). This study evaluated whether
      microvascular tumor embolism affects recurrence-free survival and correlates with
      other clinicopathologic factors after OLT among patients with HCC. From September
      1996 to June 2003, 72 OLTs for HCC were enrolled in this study. Median follow-up
      was 22.8 months. Among 41 patients without microvascular tumor embolism, 1-year,
      2-year, and 5-year recurrence-free survival rates were all 97.6%, while these
      rates were 77.3%, 68.2%, and 59.7%, respectively, for 31 patients (43.1%) with
      microvascular tumor embolism (P = .0006). The 5-year recurrence-free survival
      rate showed significant differences for a pT2 tumor (P = .0073), for maximal
      tumor size <3 cm (P = .0328), for > or =5 cm solitary tumor (P = .0095), and for
      the presence of a tumor capsule (P = .0012), within the Milan criteria (P =
      .0376). At multivariate analysis, significant independent predictors for HCC
      recurrence were microvascular tumor embolism and histopathologic grade. In
      conclusion, microvascular tumor embolism is an independent predictor of HCC
      recurrence after liver transplantation. Although OLT is a safe and effective
      treatment for HCC within the Milan criteria, the presence of microvascular tumor
      embolism at pathologic examination can predict its recurrence. In these cases,
      the feasibility of immunosuppressive therapy or adjuvant chemotherapy must be
      considered to prevent tumor recurrence.

PMID- 15848687
TI  - Recurrence rate and transplantability after liver resection in patients with
      hepatocellular carcinoma who initially met transplantation criteria.
AB  - To understand the recurrence rate and transplantability after liver resection
      (LR), which are essential factors to predict the prognosis of initial resection
      and salvage transplantation for hepatocellular carcinoma (HCC), we reviewed the
      clinical records of 279 consecutive HCC patients who met the Milan criteria and
      underwent LR between 1990 and 2000. Recurrence-free survival rates after 1, 2, 3,
      5, and 10 years following LR were 84%, 62%, 49%, 29%, and 17%, respectively.
      Multivariate analysis using clinical factors such as age, sex, histological
      differentiation, serum levels of alpha-fetoprotein and 7S domain of type IV
      collagen (7S collagen), platelet counts, indocyanin green retention test after 15
      minutes, and type of LR (resection of one or more segments, or less than one
      segment) revealed 7S collagen to be a independent factor that significantly
      affects recurrence-free survival. Yearly recurrence rates up to 5 years after
      resection ranged from 14% to 27%, averaging 20%. Concerning 169 patients who
      underwent tests for 7S collagen, the average yearly recurrence rate (27%) in
      patients with 7S collagen levels 8.0 ng/mL or higher was remarkably greater than
      that in the patients with levels less than 8.0 ng/mL (16%). The transplantability
      rate at the time of recurrence meeting the Milan criteria was roughly 60%. There
      were no pre-LR factors that significantly predicted transplantability. This
      result indicates that patients with lower 7S collagen levels are more eligible
      for initial LR and then salvage LT rather than primary LT.

PMID- 15848688
TI  - Acceptance criteria of pancreas grafts: how do surgeons decide in Europe?
AB  - OBJECTIVES: Some donor factors, such as age, cause of death, and obesity, affect
      the outcomes of pancreas transplantation. Donors with a high-risk profile are
      usually not declined for pancreas donation. The purpose of our study was to
      investigate differences between accepted and refused pancreata after being
      procured and offered. METHODS: In a retrospective study we analyzed all offered
      pancreata (n = 1360) in the "Eurotransplant Area" between May 25, 2002 and
      September 18, 2003. Included in this study were 525 pancreata transplanted
      (38.6%) and 608 pancreata refused for medical reasons (44.7%). A total of 227
      pancreata (16.7%) refused for other than medical reasons were excluded from this
      analysis. RESULTS: The significant differences in the donor profiles between
      transplanted and refused pancreata were cause of death (P < .001), donor age (P <
      .001), body mass index (BMI, P < .001), serum lipase and amylase (P < .05) at the
      time of procurement, and a history of smoking (P = .001) or alcohol abuse (P <
      .001). No differences were found for serum sodium (P = .188), blood leukocytes (P
      = .349), serum glucose at the time of procurement (P = .155), amylase and lipase
      at the time of admission (P = .34; P = .758), and vasopressor use at the time of
      admission or at the procedure (P = .802; P = .982). CONCLUSION: Even after
      procuring and offering potentially good pancreata, nearly half the organs are
      refused for medical reasons. Acceptance criteria in the Eurotransplant region
      reveal a conservative attitude toward pancreas acceptance.

PMID- 15848689
TI  - University of Wisconsin solution versus Celsior solution in clinical pancreas
      transplantation.
AB  - INTRODUCTION: This study compared the safety and efficacy of University of
      Wisconsin solution (UW) and Celsior solution (C) in pancreas transplantation
      (PTx). METHODS: A retrospective review of 154 PTx performed over a 61-month
      period included 77 grafts preserved with UW and 77 with C. The two groups were
      comparable for both donor and recipient characteristics. RESULTS: After a mean
      cold ischemia time of 624 minutes (range 360 to 945 minutes) for UW versus 672
      minutes (range 415 to 1005 minutes) for C (P = NS), no primary endocrine
      nonfunction occurred. Delayed endocrine function was diagnosed in two grafts in
      the UW group (2.6%) versus none in the C group (P = NS). After a minimum follow
      up of 4 months (mean 26.5 +/- 15.2 months), 22 recipients (UW = 11 vs C = 11; P =
      NS) required relaparotomy. Overall, 18 pancreata were lost due to either patient
      death with functioning graft (UW = 4 vs C = 1; P = NS) or graft loss due to other
      reasons (UW = 8 vs C = 5; P = NS). Actuarial 1- and 5-year patient survival rates
      were 93.5% and 86.8% for UW compared with 98.7% and 98.7% for C (P = .04).
      Actuarial graft survival rates at the same times were 88.3% and 75.0% for UW
      compared with 90.4% and 90.4% for C (P = NS). CONCLUSIONS: Within the range of
      cold ischemia times reported in this study, UW and C show similar safety and
      efficacy profiles for PTx.

PMID- 15848690
TI  - Pancreas transplants from donors aged 45 years or older.
AB  - AIMS: Since donor age of 45 years or more is considered a relative
      contraindication for pancreas transplantation (PTx), we herein report our
      experience with these donors. METHODS: Pancreases from donors aged 45 years or
      older were used in 16 of 147 PTx procedures (11%). The final decision to accept a
      graft for PTx was based mainly on the quality of visceral perfusion and the gross
      appearance of the pancreas and the vessels. There were 9 men and 7 women, ranging
      in age from 45 to 55 years (average, 48.9 years) who were donors, due to
      cerebrovascular accidents (n = 11; 68.7%). Among the donor group, 5 patients were
      receiving multiple vasopressor agents (31.2%), and 2 had a history of cardiac
      arrest (12.5%). Pancreases were transplanted either simultaneously with a
      cadaveric kidney (n = 6) or as solitary grafts (n = 10). RESULTS: After a mean
      period of cold preservation of 616 minutes (range, 475 to 844 min), delayed
      endocrine function occurred in 1 recipient (6%), who subsequently achieved
      insulin independence. Two recipients died suddenly, with functioning grafts. Two
      further grafts were lost due to portal vein thrombosis (6%) or late arterial
      thrombosis (6%). Three patients required repeat surgery (18.7%). After a mean
      follow-up period of 26.6 months, actuarial 1-year and 5-year patient survival
      rates were 87.5%, with insulin independence in 81.2% and 67.7%, respectively.
      CONCLUSIONS: Meticulous donor selection and short preservation times allow the
      safe use of pancreases procured from donors aged 45 years or older, thus
      expanding the donor pool for PTx procedures.

PMID- 15848691
TI  - Donors with a maximum body weight of 50 kg for simultaneous pancreas-kidney
      transplantation.
AB  - INTRODUCTION: Pediatric donors are rarely used for simultaneous pancreas-kidney
      transplantation (SPK). But the age of the donors may be less important than the
      body weight (BW). Therefore we retrospectively analyzed our data on SPK donors
      with a maximum BW of 50 kg. METHODS: Between June 1994 and December 2003, 22
      patients received SPK transplants from cadaveric donors with a maximum BW of 50
      kg (range, 25-50 kg; median, 42.4 kg). The median donor-recipient weight ratio
      was 0.61 (range, 0.47-0.91). RESULTS: Two kidney grafts (9.1%) displayed delayed
      graft function (2 and 9 dialyses). One patient needed insulin for 2 days (<20
      IU/d), and the other patient for 1 month at a maximum of 7 IU/d. Four pancreas
      grafts (18.2%) were lost owing to graft thrombosis. One-year survival for
      patients was 95.5%; for kidneys, 86.4%; and for the pancreas, 72.7%. After a
      median observation period of 78 months, 6 acute rejection episodes were observed
      in 5 patients (22.7%). Five acute rejections were treated successfully, but 1
      patient lost both organs. Two patients died of severe infections, at 3 months and
      3 years, respectively, after SPK. Four kidney and 3 pancreas grafts developed
      chronic allograft dysfunction. CONCLUSIONS: Our results show that 1-year graft
      function in this series was less than the results reported to the International
      Pancreas Transplant Registry. The Main reason for early pancreas loss was graft
      thrombosis (18.2%). After a median observation period of 78 months, pancreas
      graft survival was 59.1%.

PMID- 15848692
TI  - Multivariate analysis of the influence of donor and recipient cytomegalovirus
      sero-pairing on outcomes in simultaneous kidney-pancreas transplantation: the
      South-Eastern Organ Procurement Foundation Experience.
AB  - The purpose of this study was to determine if donor (D) and recipient (R) CMV
      sero-pairing at the time of simultaneous kidney-pancreas transplantation (SKPT)
      subsequently influenced outcomes in a large cohort of patients with long-term
      follow-up. Between January 1, 1997 and December 31, 1999 complete data were
      available on 723 primary SKPTs performed at South-Eastern Organ Procurement
      Foundation member institutions. For purposes of this study, four groups were
      defined: D+/R-, n = 203 (28%); D+/R+, n = 206 (28%); D-/R+, n = 156 (22%); and D
      /R-, n = 158 (22%). Patient and graft survival rates for the study groups were
      computed by Kaplan-Meier estimates and tests of equality of survival curves were
      performed utilizing both the log-rank and Wilcoxon test statistics. A
      multivariate analysis was performed using a Cox proportional hazards model and
      logistic regression. A total of 56% of Ds were CMV+ and 50% of Rs were CMV-. D
      serostatus was not, but R serostatus was, a significant independent risk factor
      for patient and kidney, but not pancreas, graft survival rates in the uncensored
      analysis. When examining the CMV D/R groups in both univariate and multivariate
      fashion, CMV sero-pairing was not an independent risk factor for death, graft
      loss, or rejection. However, when considering CMV sero-pairing as a binary
      variable (D-/R- versus all other D/R groups), 6-year patient, kidney, and
      pancreas graft survival rates were significantly higher in the D-/R- group (P <
      .05). In conclusion, CMV seronegativity is present in half of diabetic patients
      at the time of SKPT, and protective CMV seronegative matching confers a long-term
      survival advantage.

PMID- 15848693
TI  - Ninety-five percent insulin independence rate 3 years after pancreas
      transplantation alone with portal-enteric drainage.
AB  - AIMS: Portal-enteric drainage (PED) might be particularly suitable for pancreas
      transplantation alone (PTA), since it has been associated with an immunologic
      advantage and achieves excellent metabolic results. We describe our experience
      with a consecutive series of 40 PTAs with PED. METHODS: Between April 2001 and
      March 2004, 40 consecutive PTAs were performed with PED. Recipients were selected
      according to the American Diabetic Association recommendations. Donors were
      selected according to standard criteria irrespective of HLA match, although
      matching for A and B loci was considered at the time of graft allocation.
      Immunosuppression consisted of induction treatment with basiliximab (n = 34) or
      thymoglobulin (n = 6), and maintenance therapy with steroids, mycophenolate
      mofetil, and tacrolimus. RESULTS: After a mean cold ischemia time of 690 minutes
      (range, 517-965 min) all pancreases functioned immediately. Three grafts were
      lost due to hyperacute or accelerated rejection. No graft was lost to vascular
      thrombosis, although 5 (12.5%) nonocclusive thromboses were identified and the
      grafts were rescued with intravenous heparin infusion. A repeat laparotomy was
      required in 7 recipients (17.5%) No patient required multiple repeat
      laparotomies, and none died. After a mean follow-up of 16.4 months (range, 1-36
      mo), 2 recipients were diagnosed with rejection episodes, which were reversed
      with steroid boluses. Actuarial 3-year patient, and graft survival rates were
      100% and 94.9%, respectively. The following parameters showed significant
      improvement compared with pretransplantation evaluation: hemoglobin A1C
      concentration, total and high-density lipoprotein cholesterol levels, arterial
      blood pressure, cardiac performance, retinopathy, proteinuria, and neuropathy.
      CONCLUSIONS: Pancreas transplantation alone with PED provides high rates of long
      term insulin-independence.

PMID- 15848694
TI  - Successful solitary pancreas transplantation with portal-enteric drainage
      following unsuccessful islet cell transplantation.
AB  - BACKGROUND: There are no data regarding the outcome of solitary pancreas
      transplantation (SPT) with portal venous drainage (PVD) following unsuccessful
      islet transplantation (ITx) after multiple islet injections into the portal vein.
      We herein describe the outcome of three SPTs with PVD performed after failed ITx.
      METHODS: Between October 2002 and December 2003, three SPTs with PVD were
      performed following unsuccessful ITx with multiple intraportal islet injections
      (mean 2.3 injections: range 2 to 3 injections) in two women and one man, aged 26,
      49, and 60 years. Panel reactive antibody titer was 0% in all recipients.
      Immunosuppression was based on induction with either basiliximab (n = 2) or
      thymoglobulin (n = 1); maintenance therapy included steroids, mycophenolate
      mofetil, and tacrolimus. During the recipient operation, the absence of venous
      hypertension was established by direct measurement of portal pressure, before
      making the final decision to drain the pancreas into the portal vein. RESULTS:
      Portal pressures were 16 cm H2O, 14 cm H2O, and 13 cm H2O. Pancreas grafts were
      reperfused after a period of cold preservation of 638, 695, and 835 minutes,
      respectively. All grafts showed immediate endocrine function, maintaining their
      recipients insulin-independent for longest follow-ups of 8, 21, and 23 months,
      respectively. One recipient developed a nonocclusive venous thrombus that
      resolved with intravenous heparin infusion. CONCLUSIONS: Our experience showed
      that unsuccessful ITx with multiple intraportal injections does not necessarily
      preclude the possibility of subsequent successful SPT with PVD. Further
      experience is needed to define contraindications and possible complications of
      SPT with PVD following ITx.

PMID- 15848695
TI  - Graft survival and immune regulation of pancreas allograft recipients induced
      with thymoglobulin, sirolimus, and cyclosporine.
AB  - BACKGROUND: Our objective was to determine the impact of thymoglobulin-sirolimus
      cyclosporine immunosuppression on the alloimmune response of pancreas-kidney
      transplant recipients. METHODS: Thirty-six pancreas transplant recipients
      received an induction protocol of thymoglobulin, sirolimus, reduced-dose
      cyclosporine, and corticosteroids. A subset of 10 recipients were also enrolled
      in a study to measure immune responsiveness. Flow PRA-determined HLA antibody,
      donor-specific flow cytometry crossmatching (FCXM), T-cell subset, and suppressor
      cell assays were performed at various timepoints during the first posttransplant
      year. RESULTS: One-year patient, kidney, and pancreas survivals were 97%, 94%,
      and 92%, respectively. There was 1 death due to sepsis, and 1 kidney and 2
      pancreas graft losses. There were no acute rejection episodes. Recipients in the
      immune-monitoring study displayed depression of CD3, CD4, and CD8 counts (<80%)
      until 3 months posttransplant. At transplantation, 9 of 10 patients displayed
      <10% class I HLA antibody. By 3 months, 7 of 10 showed a transient elevation in
      class I HLA antibodies, with 2 patients expressing >80% flow PRA. At transplant 1
      patient was FCXM-positive, whereas, by 3 months posttransplant, 2 of 10 patients
      demonstrated a positive FCXM. There were no clinical consequences to either the
      presence of HLA antibody or the positive FCXMs. By 6 months, 7 of 9 patients
      expressed immunoregulatory suppressor cell activity. CONCLUSIONS: The absence of
      acute rejection events was likely due to inhibition of donor-specific immunity.
      Seventy percent of patients demonstrated an early non-donor-directed HLA antibody
      response that had no adverse effect on graft function and 78% of the patients
      displayed immunoregulatory suppressor cell function, probably contributing to the
      successful clinical outcome.

PMID- 15848696
TI  - Simultaneous pancreas-kidney transplants in type I and type II diabetic patients
      with end-stage renal disease: similar 10-year outcomes.
AB  - INTRODUCTION: Herein we report 10- to 15-year results of simultaneous pancreas
      kidney (SPK) transplants in 135 type I and type II insulin-dependent diabetes
      mellitus (IDDM) patients. METHODS: Diabetes type was defined by the absence (type
      I) or presence (type II) of C-peptide. The freedom from dialysis and need for
      insulin defined graft survival. Patient survival was verified by record review
      and the Social Security Death Registry. The mean follow-up exceeded 100 months.
      RESULTS: Type II IDDM present in 28% of the 135 cohort, predominately among
      African-Americans (AA). The type II group was two-thirds AA (43% of the total AA
      patients) and 17% of the non-African-American (nAA) group. The difference between
      the two groups by C-peptide level was significant (P = .001). Type II patients
      had a higher body mass index, were slightly older at the onset of DM, but had
      similar duration of IDDM before ESRD. At 5 and 10 years, pancreas survival for
      type 1 DM was 71% and 49%; for type II DM it was 67% and 56% (P = .52). Kidney
      survival for type I DM was 77% and 50%; for type II it was 72% and 56% (P = .65).
      Patient survival for type I DM was 85% and 63%; for type II DM it was 73% and 70%
      (P = .98). CONCLUSIONS: We conclude that the outcomes of SPK transplants are
      equivalent regardless of diabetes type. Accordingly, the decision whether to
      perform pancreas transplants in diabetic recipients of kidney allografts should
      be based on general acceptance criteria not diabetes type.

PMID- 15848697
TI  - Comparable kidney graft survival of type 1 diabetics treated with simultaneous
      pancreas-kidney transplantation and nondiabetic patients treated with cadaveric
      renal transplantation.
AB  - Simultaneous pancreas-kidney transplantation (SPK) is now a common treatment for
      insulin-dependent diabetic patients with end-stage renal disease. This study
      analyzed the patient and graft survival rates of 231 kidney transplantations
      (KTX) in nondiabetic patients and of 95 SPK in diabetic patients between January
      1, 1998 and December 31, 2001. The SPK group showed significantly better patient
      and graft survival rates after 5 years than the KTX group (96% and 90% vs 85% and
      75%, respectively; P < .05). Even the serum creatinine level during the first 2
      years showed significantly lower levels in the SPK group (P < .01). The patients
      in the SPK group were significantly younger. They received organs from younger
      donors than the patients in the KTX group (P < .01). The cold ischemia time and
      the time on previous dialysis were also shorter in the SPK group (P < .01).
      However, the number of HLA mismatches was higher in the SPK patients (P < .01).
      Limiting the analysis to recipients younger than 60 years, donors younger than 58
      years, and cold ischemia time to <19 hours, there was no difference in graft or
      patient survival. These data suggest that donor and recipient age as well cold
      ischemic time have a greater impact on early outcome and postoperative
      complications of renal transplants than HLA matching.

PMID- 15848698
TI  - Pilot study of early corticosteroid elimination after pancreas transplantation.
AB  - Early corticosteroid withdrawal has recently been shown to be possible in
      recipients of simultaneous pancreas kidney transplants; however, its feasibility
      in solitary pancreas recipients has not been documented. In the present study, we
      provide evidence that early withdrawal can be achieved in pancreas as well as
      pancreas-kidney recipients. METHODS: Twenty type I diabetics underwent 13
      pancreas-kidney transplants and 7 pancreas-only transplants with early withdrawal
      (methylprednisone 6-day taper). Additional immunosuppression consisted of
      tacrolimus, mycophenolate mofetil, and thymoglobulin induction (five doses).
      RESULTS: Transplants included 13 pancreas-kidney, 6 pancreas after kidney
      transplant, and 1 pancreas after islet transplant. Overall mean follow-up was 7.3
      months. One episode of pancreas transplant rejection after pancreas-only
      transplant was detected on protocol biopsy without biochemical abnormalities. One
      renal allograft rejection occurred 65 days posttransplant in a pancreas-kidney
      recipient and was graded as a Banff IA rejection. A single pancreas graft loss
      occurred due to thrombosis 6 days after pancreas-kidney transplantation.
      CONCLUSIONS: These results indicate that relatively short thymoglobulin induction
      (five doses) with tacrolimus and mycophenolate mofetil can allow early withdrawal
      in both pancreas-kidney and pancreas-only transplant recipients.

PMID- 15848699
TI  - A multicenter analysis of the significance of HLA matching on outcomes after
      kidney-pancreas transplantation.
AB  - The purpose of this study was to determine the influence of HLA matching on
      outcomes in simultaneous kidney-pancreas transplant (SKPT) recipients in a
      multicenter trial. From March 1999 to May 2001, a total of 297 SKPT recipients
      were enrolled in a prospective randomized trial of 2 daclizumab dosing strategies
      versus no antibody induction in combination with tacrolimus, mycophenolate
      mofetil, and steroids in SKPT recipients. Subanalyses using both univariate and
      multivariate models were performed at 1 year to identify factors associated with
      acute rejection, graft loss, or death. Potential risk factors evaluated were
      treatment group, African American ethnicity, HLA-A mismatches (MM), HLA-B MM, HLA
      DR MM, total HLA MM, surgical technique, cytomegalovirus status of donor and
      recipient, and delayed graft function (DGF). Univariate analyses revealed that
      treatment group, HLA-A MM, HLA-B MM, total HLA MM >3, and DGF were significantly
      associated with acute rejection. These variables were then entered into logistic
      and Cox regression analyses. HLA-A MM and DGF were the only variables that
      remained significantly associated with acute rejection in the multivariate model.
      The relative risk for acute rejection in recipients with HLA-A MM was 1.56 (P =
      .02). In conclusion, despite contemporary immunosuppression, the degree of HLA
      MM, particularly HLA-A, and DGF are associated with an increased risk for acute
      rejection in SKPT recipients at 1 year. Less rejection was noted in patients with
      0 MM at all 3 HLA loci and in patients with total HLA-MM <3. However, none of
      these factors affected short-term patient or graft survival rates.

PMID- 15848700
TI  - Surgical nuances in pancreas transplantation.
AB  - The modern surgical era of vascularized pancreas transplantation (PTX) began with
      the systemic-bladder drainage technique. According to International Pancreas
      Transplant Registry (IPTR) data, most PTX procedures are performed with systemic
      venous delivery of insulin and either bladder (systemic bladder) or enteric
      (systemic-enteric) drainage of the exocrine secretions. Since 1995 the number of
      PTX procedures performed with primary enteric drainage has increased
      dramatically, accounting for more than 70% of cases since 2001. Despite an
      evolution in exocrine drainage, the proportion of enteric drained PTXs with
      portal venous delivery of insulin (portal enteric drainage) has remained low,
      representing about 20% of cases. In recent IPTR analyses no differences were
      reported in short-term outcomes according to surgical technique. Coincident with
      more physiologic implantation techniques, the surgical complication rate has
      decreased to 10% to 20%. Experience with donor and recipient selection can reduce
      morbidity, inasmuch as risk factors for surgical complications include prolonged
      pre-transplantation peritoneal dialysis, donor or recipient BMI body mass index
      >28 kg/m2, donor or recipient age older than 45 years, cerebrovascular cause of
      donor brain death, prolonged preservation, and prior abdominal surgery in the
      recipient. New techniques include simultaneous living donor kidney and deceased
      donor PTX, gastroduodenal artery revascularization, laparoscopic living donor
      nephrectomy and distal pancreatectomy, en bloc kidney and pancreas
      transplantation, P-E drainage with venting jejunostomy, retroperitoneal PTX with
      P-E drainage, and unusual vascular grafts. In the future the emphasis will shift
      from short-term surgical to long-term medical outcomes as the ultimate measure of
      success.

PMID- 15848701
TI  - Pilot study of rapid steroid elimination with alemtuzumab induction therapy in
      kidney and pancreas transplantation.
AB  - This study evaluates our initial experience using alemtuzumab induction with
      rapid corticosteroid elimination in kidney (KTX) and pancreas transplant (PTX)
      patients. Data were collected retrospectively for all patients who received
      single-dose alemtuzumab (30 mg IV intraoperatively) with steroid pretreatment and
      a control group who received alternate day rabbit antithymocyte globulin (rATG)
      induction with a steroid-based regimen. Patients in both groups received
      tacrolimus (TAC) and mycophenolate mofetil (MMF). There were 16 patients in each
      group, including 9 deceased donor KTXs, 5 living donor KTXs, 1 simultaneous K
      PTX, and 1 sequential PTX after KTX. Demographic, immunologic, and transplant
      characteristics were similar between groups. Nine patients (56%) in the
      alemtuzumab group compared to five (25%) in the control group developed
      neutropenia requiring MMF or valganciclovir dose reduction (or both). Absolute
      lymphocyte counts at 3 months were 340 +/- 200/mm3 and 890 +/- 544/ mm3 in the
      alemtuzumab and control groups, respectively (P = .001). There were two biopsy
      proven acute rejection episodes (12.5%) in each group, and no difference in the
      incidence of infection. Creatinine clearance at 6 months was 58 mL/min in each
      group. Patient and kidney graft survival rates were both 94% in the alemtuzumab
      group (one death from cardiac arrest), compared with 100% patient and kidney
      graft survival rates in the control group (P = NS), with a mean follow-up of 9
      and 11 months, respectively. The results of this pilot study suggest that similar
      short-term outcomes can be achieved using a rapid steroid elimination protocol
      with alemtuzumab induction therapy compared to rATG with steroids in patients
      receiving TAC and MMF maintenance therapy.

PMID- 15848702
TI  - Incidence of coronary heart disease and cardiac events in patients undergoing
      kidney and pancreatic transplantation.
AB  - One major cause of graft loss after kidney transplantation or simultaneous kidney
      and pancreas transplantation is death of the recipient due to cardiac events.
      Records of 261 patients who underwent sole kidney (group A) or combined kidney
      pancreas transplantation (group B) were retrospectively analyzed. Patients were
      divided into groups with basic cardiac evaluation (chest X-ray,
      electrocardiogram) and patients with additional diagnostics [echocardiography,
      exercise stress test, myocardial perfusion test, and coronary angiography (CAG)].
      The results of the performed CAGs were as follows: proven coronary artery disease
      (CAD) in 22 patients (12.43%) in group A and 37 patients (44.05%) in group B;
      stenosis of one main coronary artery of 70% or greater in 8.47% (group A) and
      16.67% (group B) of the patients. Subsequent revascularization procedures were
      performed in 15 candidates (8.47%) of group A and 11 (13.10%) of group B. The
      incidence of posttransplant cardiac events (PCE) was lower in recipients in both
      groups who underwent additional cardiac evaluation. Late postoperative deaths
      were reported in 3.45% of kidney recipients with no additional evaluation (group
      A), in 2.06% of patients with further diagnostics (group A), and in only 1.19% of
      patients with invasive pretransplant evaluation (group B). Patients with known
      CAD and no further invasive diagnostics or subsequent revascularization are at
      great risk. PCE were observed in three of seven patients in this subgroup.
      Careful cardiac evaluation including echocardiography, exercise stress test,
      myocardial perfusion test, and CAG is associated with a low incidence of PCE.

PMID- 15848703
TI  - Single-shot antithymocyte globulin (ATG) induction for pancreas/kidney
      transplantation: ATG-Fresenius versus Thymoglobulin.
AB  - Single-shot antithymocyte globulin (ATG) prior to reperfusion followed by
      tacrolimus (TAC), mycophenolate mofetil (MMF), and prednisolone (PRD) is an
      established induction therapy in simultaneous pancreas kidney transplant (SPK)
      recipients. We retrospectively analyzed 6-month data from 105 patients who
      received their first SPK. From January 1996 to December 2000, ATG-Fresenius was
      used. Since January 2001, Thymoglobulin has been administered. In the first
      group, 58 patients were treated with ATG-Fresenius (4-6 mg/kg body weight). In
      the second group, 47 patients received Thymoglobulin (1.5-2.5 mg/kg body weight).
      HLA-mismatch was comparable. After an observation period of 6 months, patients,
      kidney, and pancreas graft survival is 98.3%, 96.6%, and 93.1% in group I and
      97.9%, 97.9%, and 85.1% in group II, respectively. In each group, one death with
      functioning graft (DWFG) was observed. Twenty (34.5%) acute rejection episodes
      (AR) were observed (18 patients) in group I. They were treated with steroids (n =
      16) or steroids/OKT3 (n = 4). One kidney graft failure was observed due to
      rejection and one due to DWFG. Four pancreas grafts were lost (thrombosis, n = 2;
      AR, n = 1; DWFG, n = 1). In group II, 15 AR (31.9%) were seen in 12 patients and
      were treated with steroids (n = 12), steroids/ATG (n = 1), or steroids/OKT3 (n =
      2). Seven pancreas (thrombosis, n = 5; rejection, n = 1; DWFG, n = 1) and one
      kidney (DWFG, n = 1) graft losses occurred. These data clearly establish that
      single-shot ATG prior to reperfusion, followed by TAC, MMF, and PRD results in a
      low incidence of AR (34.5% in group I and 31.9% in group II) after SPK. Only 6.9%
      (group I) and 6.4% (group II) of the patients received antibodies for rejection
      treatment.

PMID- 15848704
TI  - Results from the inaugural year of the Collaborative Islet Transplant Registry.
AB  - The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
      established the Collaborative Islet Transplant Registry (CITR) in September 2001.
      In its inaugural year, CITR represents the efforts of 12 collaborating North
      American islet transplant centers reporting 86 islet transplant recipients' data
      (1999-2003) and 173 processed pancreata leading to 158 infusion procedures.
      Recipient median age was 42.2 years, duration of diabetes was 30 years, and over
      66% of the recipients were female. Twenty-eight patients received a total of 1
      islet infusion, 44 patients received 2 islet infusions, and 14 patients received
      3 islet infusions. The median age of the deceased donor was 44 years and body
      mass index was 28.2. Median time from cross clamp to pancreas recovery was 27
      minutes, while duration of cold ischemia was 7 hours. Over 77% of the processing
      facilities used a density gradient for islet purification. For recipients of only
      1 infusion, approximately 8665 total islet equivalents/kg were infused;
      recipients of 2 infusions received 14,102 islet equivalents/kg, and recipients of
      3 infusions received 22,922 islet equivalents/kg. At 6 months after the last
      infusion, 61.1% of the recipients were reported to be insulin independent; at 12
      months, 57.9% were reported to be insulin independent. There have been no deaths
      reported to CITR; 45 serious adverse events were reported. Through its
      collaboration with the islet transplant community and its interaction with
      professional societies and federal agencies, CITR is positioned to provide
      current and comprehensive information on clinically significant outcome measures
      in islet transplantation.

PMID- 15848705
TI  - The standardization of pancreatic donors for islet isolation.
AB  - INTRODUCTION: Islet transplantation has proven to be a successful treatment for
      insulin-dependent diabetes mellitus (IDDM). The aim of this study was to
      establish an algorithm by which the combination of the donor quality and pancreas
      quality was given a numerical score from 0 to 100 for use in determining the
      quality of a pancreas for islet isolation. METHODS: In this study we
      retrospectively analyzed 326 pancreata and the outcomes of their respective
      isolations. Specific donor variables and physical characteristics were identified
      and weighted according to their influence on the success of the isolation. For
      each variable, ranges and point weightings were established based on our
      laboratory experience and literature review. RESULTS: Analysis of the data showed
      a strong association of the donor point with isolation outcome. Pancreata with
      lower donor point scores had lower transplant success rates, while higher donor
      point scores in turn produced higher transplant rates. CONCLUSION: This scoring
      system has proven to be effective in assessing the potential of pancreata for a
      favorable isolation outcome. By analyzing the final score of the pancreas, a
      standardized decision can be made on whether to accept or decline the pancreas.
      Another benefit of the scoring system is that it is a quick and efficient way to
      trend the quality of donor organs.

PMID- 15848706
TI  - Examination of the molecular signature associated with islet dysfunction.
AB  - The aim of this study was to identify the molecular signatures that are
      predictive of nonfunctional islet preparations. We examined functional outcomes
      of six islet preparations accepted for research purposes from human donors. Islet
      were maintained on culture in M-SFM media for 7 to 14 days then transplanted into
      NOD-SCID mice. At the time of transplant, RNA was extracted from a second aliquot
      of cultured islets for expression analysis. We also performed gene expression
      analysis using high-density Affymetrix U133A GeneChips on these preparations.
      Among 1833 genes selected, hierarchical clustering was performed using the
      GeneSpring software package (Silicon Genetics, Inc.), where 754 genes (higher in
      nonfunctional) and 177 genes (lower in nonfunctional) were differentially
      expressed with tight pattern of expression. Islets with low functionality showed
      high relative levels of expression of hypoxia-induced genes and increased
      frequency of expression of proinflammatory and proangiogenic genes, such as
      vascular endothelial growth factor. Conversely, nonfunctional islets had low
      levels of insulin-processing message. The general profile of these low
      functionality islets shows attempted recovery from hypoxic assault and little
      effort directed toward insulin production and secretion. Further identification
      of the molecular signature of nonfunctional islets could allow the development of
      a potency assay for human transplantation.

PMID- 15848707
TI  - Technical improvement of human pancreatic islet isolation.
AB  - INTRODUCTION: A key factor for successful islet isolation is to place the optimal
      amount of enzyme into the pancreatic ducts prior to starting digestion of
      pancreatic glands. To improve this procedure, we introduced novel techniques to
      identify and repair tissue damage resulting in leakage of collagenase solution.
      MATERIALS AND METHODS: One hundred twelve standardized consecutive islet
      isolations were for the effects of dye and glue on islet yield, islet function
      using a perifusion assay, and the possibility of clinical transplantation. One
      group of pancreata (n = 26) obtained en bloc together with duodenum were
      carefully detached with ligation of accessory ducts in an isolation unit (WPD
      group), whereas the pancreata were dissected from the duodenum in the operating
      room in the other 86 isolations. In 28 of 86 isolations, whole glands were used
      (WP group), while only the body and tail area were applied in the remaining 58
      isolations (PP group). RESULTS: Both dye and glue effectively prevented leakage
      of collagenase from the gland. Both islet yield and success rate were higher with
      these tools without adverse effects on islet function or collagenase activity.
      The success rate of isolations and islet yield were significantly higher in the
      WPD group (P = .02 and .001, respectively). CONCLUSIONS: Dye and glue may be
      useful tools to improve human islet isolation procedures. In addition, the use of
      the whole pancreas further improves the outcome.

PMID- 15848708
TI  - Key factors for human islet isolation and clinical transplantation.
AB  - BACKGROUND: To further improve the outcome of clinical islet transplantation
      analysis of the impact of donor- and process-related factors could be of great
      importance. MATERIALS AND METHODS: Thirty-eight consecutive clinical islet
      transplantations were performed with consecutive islet isolations. Univariate
      analysis for donor- and isolation-related variables were correlated with
      recipient C-peptide levels at 2 and 4 weeks after transplantation. "Warm ischemia
      time" was defined as the time from start of University of Wisconsin solution
      perfusion in the donor until the pancreas was removed to the back table. RESULTS:
      Short "warm ischemia time" (WIT), low expression of tissue factor (TF) in
      pancreatic tissue, and high creatinine levels in the donor were variables related
      to high C-peptide values after islet transplantation. Furthermore,
      hospitalization length longer than 4 days was associated with low C-peptide
      levels. The number of islet equivalents (IEQ) did not correlate with the clinical
      outcome, possibly due to the fact that IEQ number was included in the release
      criteria for clinical islet transplantation CONCLUSIONS: Successful clinical
      islet transplantation is strongly correlated with donor and pancreas procurement
      factors rather than isolation process-related variables. "WIT" may induce TF
      expression in the pancreatic tissues. TF has been identified as the main trigger
      of the instant blood-mediated-inflammatory reaction in clinical islet
      transplantation. Therefore, assay of TF expression in pancreatic tissues could be
      applied as useful screening tool to identify "good" pancreata for clinical
      transplantation.

PMID- 15848709
TI  - Analysis of large-scale nonhuman primate islet isolations.
AB  - AIMS: It is important to have clinically relevant large animal models, especially
      nonhuman primates, to improve the efficacy of islet isolation and transplantation
      prior to clinical trials. The aim of this study was to improve the efficacy of
      islet isolation by analyzing large-scale nonhuman primate islet isolations.
      METHODS: Sixty-one islet isolations were evaluated using nonhuman primates. An
      automated isolation method was scaled down for islet isolation. Islet yields of
      prepurification, postpurification, and postculture, purity of islets, viability
      of islets, and functionality with glucose stimulation test were assessed.
      Initially, we analyzed relationships between endpoints then analyzed additional
      factors for successful islet isolation. Those factors included donor
      characteristics, the two-layer method (TLM) of pancreas preservation, trypsin
      inhibition during digestion, and digestion and collection time. RESULTS:
      Prepurification islet yields were strongly correlated with postpurification
      yields and postculture yields. It weakly but significantly correlated with
      purity, viability, and functionality. The average prepurification yield was
      16,267 IE/g with each case divided into either above-average (high-yield group)
      or below-average groups (low-yield group). In 8 cases, TLM and trypsin inhibition
      were used and all cases belonged to the high-yield group. There were no
      significant differences between high- and low-yield groups in terms of donor age,
      body weight, pancreas weight, and cold ischemic time. The high-yield group had
      significantly longer digestion times and shorter collection times. CONCLUSIONS:
      TLM, trypsin inhibition, complete digestion, and quick collections were key for
      successful islet isolation. Analysis of nonhuman primate islet isolation
      techniques provided useful information, which should help to improve clinical
      islet transplantation.

PMID- 15848710
TI  - In the search of potential human islet stem cells: is tetranectin showing us the
      way?
AB  - Pancreatic islet cell transplantation is a promising approach to restore the
      required mass of functional beta cells in diabetic patients as a means to achieve
      long-term normoglycemia. This therapy is, however, not yet widely used, in part
      because of the shortage of human islet cells. Gaining detailed knowledge of the
      physiological basis governing the processes of differentiation of pancreatic stem
      or progenitor cells and the mechanisms and molecules necessary for a successful
      engraftment of the transplanted cells into the liver is instrumental for the
      ambitious goal of engineering new pancreatic islets to cure type I diabetes. We
      describe the in vivo and in vitro localisation of tetranectin (TN) in human and
      murine islet cells. Similar to human islets, murine islets stain positive for
      tetranectin. The amount and localization of TN is influenced by different culture
      conditions. The ability of TN to bind plasminogen indicates that it may have a
      role in regulating pericellular proteolysis and proteolytic activation of latent
      forms of metalloproteinases and growth factors. Tetranectin may thereby play an
      important role in the survival of islets in the liver after islet
      transplantation. TN-positive cells can be isolated and maintained in culture
      after human islet isolation, thereby providing the possibility to further clarify
      its role and function in vivo as well as in the course of islet transplantation.

PMID- 15848711
TI  - Impact of a sirolimus/tacrolimus-based immunosuppressive regimen on kidney
      function after islet transplantation.
AB  - AIM: Islet transplantation is gaining recognition as a therapeutic option for
      selected diabetic patients. The immunosuppressive regimen based on sirolimus/low
      dose tacrolimus is considered a major breakthrough that allowed considerable
      improvement in graft survival. A high incidence of side effects associated with
      such a regimen has been reported in the literature, but this immunosuppressive
      protocol is generally considered safe or even protective to the kidney. Herein,
      we analyze the impact of the sirolimus/low-dose tacrolimus-based protocol on
      kidney function. PATIENTS AND METHODS: Five islet-after-kidney and 5 islet
      transplant-alone patients were enrolled and followed up. Renal function was
      assessed by the periodic measurement of serum creatinine and by the presence of
      albuminuria. Metabolic control markers and graft function were followed, as well
      as immunosuppressive whole blood trough levels. RESULTS: Kidney function
      significantly decreased in 6 of 10 patients. Neither metabolic markers nor
      immunosuppressive drugs levels were significantly associated with the decreased
      kidney function. CONCLUSION: Although a specific etiology was not identified,
      subsets of patients presented a higher risk for decrease of kidney function. The
      presence of low creatinine clearance, albuminuria, and long-established kidney
      graft were associated with poorer outcomes.

PMID- 15848712
TI  - Donor heart selection: Wythenshawe experience.
AB  - BACKGROUND: The decline in the number of suitable donor hearts has led to an
      increasing interest in the use of previously unacceptable donors. This study
      aimed to evaluate the outcome of recipients of donor hearts considered medically
      unsuitable for transplantation at this center that were used in other centers in
      the United Kingdom. METHODS: Forty donor hearts (group 1) were declined by
      Wythenshawe Hospital and used in other units in the United Kingdom in the period
      extending from April 1998 to March 2003. One hundred four hearts (group 2) were
      transplanted at Wythenshawe Hospital during the same period. Donors and recipient
      data were obtained from the United Kingdom Cardiothoracic Transplant Audit
      database. Mortality in both groups was analyzed using SPSS software. RESULTS:
      Mortality in patients receiving grafts from group 1 donors was significantly
      higher than in group 2 (P < .0009). Of the early deaths in this group 50% (6 of
      12) were the result of graft failure. These donors were receiving high doses of
      inotropes, had ischemic time exceeding 3.5 hours, and the grafts were
      transplanted into high-risk patients. CONCLUSION: Hearts declined on medical
      grounds by one center should be evaluated with caution before being considered
      suitable for transplantation, especially when more than one adverse factor is
      present.

PMID- 15848713
TI  - Daclizumab is associated with decreased rejection and no increased mortality in
      cardiac transplant patients receiving MMF, cyclosporine, and corticosteroids.
AB  - BACKGROUND: Sparse published data exist on outcomes in daclizumab-treated cardiac
      transplant patients. One trial observed an increased mortality risk 6 and 12
      months posttransplant in patients receiving daclizumab plus mycophenolate mofetil
      (MMF), cyclosporine, and steroids. This study further investigates the safety
      profile of daclizumab with this same immunosuppressive regimen from a large
      registry. METHODS: Data obtained at hospital discharge on all adult cardiac
      transplants performed in the USA between January 1998 and October 2003 for
      patients receiving MMF plus cyclosporine and steroids were accessed from the
      Scientific Registry of Transplant Recipients. Patients were selected based on
      induction treatment: daclizumab (n = 684) or no induction (n = 2525). Outcomes
      were evaluated at 6 months, 12 months, and 3 years posttransplant. Univariate
      Kaplan-Meier and multivariate Cox models were used to evaluate the effect of
      treatment on outcomes. Patient survival and infectious death were the primary
      endpoints. Secondary endpoints included rejection within the first year
      posttransplant (acute rejection; AR) and total rejection episodes over time. The
      two treatment groups shared similar demographics and transplant procedure
      details. RESULTS: Daclizumab (vs no induction) patients had no increased risk of
      patient death nor infectious death. Daclizumab patients had a lower incidence of
      AR at 6 months (P = .005) and 12 months (P < .001); the adjusted risk for AR at
      12 months (hazards ratio [HR] = 0.77; P = .89) and over 3 years (HR 0.83, P =
      .006) was also lower in daclizumab-treated patients. CONCLUSIONS: In cardiac
      transplant patients, daclizumab (vs no induction) does not result in increased
      mortality or infectious death, and is associated with a lower incidence of AR.

PMID- 15848714
TI  - Phenylethanolamine N-methyltransferase gene expression in transplanted human
      heart.
AB  - BACKGROUND: Phenylethanolamine N-methyltransferase (PNMT) is an enzyme involved
      in the epinephrine synthesis. The aim of this study was to investigate PNMT gene
      expression in the transplanted human heart in relation to the time elapsed from
      heart transplantation (HTx) and selected clinical characteristics. PATIENTS AND
      METHODS: The messenger RNA (mRNA) levels of PNMT in myocardial tissue were
      determined in 22 (21 males) patients at 0-12 years after HTx. Relative
      quantification of mRNA levels was performed using reverse transcription and
      polymerase chain reaction (RT-PCR) for correlation with heart rate (HR), blood
      pressure (BP), parameters of heart rate variability, and graft systolic and
      diastolic functions. RESULTS: During the first 3 years after HTx, PNMT mRNA
      levels were higher (mean +/- SEM) (0.75 +/- 0.06; n = 12) compared with later
      years (0.33 +/- 0.06; n = 10); (P < .01). HR variability in the low frequency
      band of the power spectrum (LF) was lower among patients during the first 3 years
      after HTx (2.73 +/- 0.31 vs 5.67 +/- 0.69 ms; P < .01). A significant negative
      linear correlation was observed between PNMT mRNA and LF (P = .05; r = -0.47). No
      association was noted between HR, BP, parameters of systolic or diastolic
      function, standard deviation of all RR intervals, or high frequency (0.15-0.40
      Hz) bands of the 24-hour RR interval power spectrum. CONCLUSION: This work
      provides the first evidence of the presence of local PNMT transcription in human
      heart after HTx. Appearance of PNMT transcription in the myocardium after HTx may
      reflect autonomous "sympathicotrophy." Decreased PNMT expression with time
      elapsed after HTx suggests graft reinervation.

PMID- 15848715
TI  - Usefulness of stanford scale of intimal hyperplasia assessed by intravascular
      ultrasound to predict time of onset and severity of cardiac allograft
      vasculopathy.
AB  - BACKGROUND: The purpose of this study was to assess the prognostic value of a
      single IVUS result described by the Stanford scale to predict CAV development.
      METHODS: Inclusion criteria were heart transplantation (OHT) before 1997 and at
      least one IVUS performed before 1998. IVUS studies were performed in 37 patients
      at 37 +/- 26 months after OHT. Based on the Stanford scale, were divided patients
      into Four groups: group I (grade 0 or 1): n = 4, 42 +/- 19 years, 2 men/2 women;
      group II (grade 2): n = 10, 44 +/- 15 years, 9 men/1 woman; group III (grade 3):
      n = 11, 48 +/- 11 years, 11 men; and group IV (grade 4): n = 12, 46 +/- 8 years,
      12 men. We compared the incidence and time of onset of clinically significant
      CAV, namely significant coronary lesions, myocardial infarction and death caused
      by CAV. RESULTS: There was no CAV diagnosed in group I. The rates of CAV in
      coronary angiograms in groups II, III and IV were: 80%, 36%, and 75%,
      respectively. Significant CAV was found in 30%, 9%, and 50% of patients,
      respectively. Average times of onset of any CAV in groups II, III and IV were
      4.9, 5.6, and 3.3 years, and for significant CAV were 4.1, 3.6, and 5.5 years,
      respectively. Deaths in groups I to IV were 1, 4, 2, and 5, respectively. CAV was
      the reason for death in 1 patient from group III, and 3 patients from group IV.
      CONCLUSIONS: Extreme grades on the Stanford scale (0, 1, and 4) describing a
      single IVUS study in OHT recipients appear useful to stratify patients with the
      lowest versus the highest risk of CAV development.

PMID- 15848716
TI  - Usefulness of pulmonary hypertension reversibility test with sodium nitroprusside
      in stratification of early death risk after orthotopic heart transplantation.
AB  - AIM: To assess the prognostic value of a PH reversibility test with NPS to
      predict early death risk after orthotopic heart transplantation (OHT). MATERIALS
      AND METHODS: We analyzed the results of 94 consecutive OHT procedures performed
      from 2002 to 2003. Pulmonary vascular resistance (PVR) and transpulmonary
      gradient (TPG) were assessed as part of the routine pre-OHT evaluation. PH was
      excluded in 57 patients (61%, group A); TPG > or = 12 mmHg and/or PVR > 2.5 Wood
      units were observed in 37 patients (39%). Sixteen patients underwent a PH
      reversibility test with NPS: 9 patients (group B) achieved normal TPG and PVR
      without a drop in systolic arterial pressure (BP(s) > 85 mmHg), while a marked
      decrease of BP(s) (< 85 mmHg) during NPS infusion was observed in 7 patients
      (group C). Then, 21 patients were selected for OHT despite PH without any
      reversibility test. We compared the number of early deaths after OHT among groups
      (chi-square test). RESULTS: The 30-day death rate was 7% in group A, 11% in group
      B, 71% in group C, and 29% in group D. (A vs C, P = .0001 and A vs D, P = .03).
      Right ventricle or biventricular failure was the cause of death in 1 patient in
      group A, 1 patient in group B, 5 patients in group C, and 6 patients in group D
      (A vs C, P < .0001 and A vs D, P = .0012). CONCLUSION: PH reversibility revealed
      with NPS does not increase the risk of early death after OHT unless there is an
      absence of marked fall in systemic pressure.

PMID- 15848717
TI  - Early and late rejection and HLA sensitization at the time of heart
      transplantation in patients bridged with left ventricular assist devices.
AB  - Over the years, the frequency of heart transplant candidates with HLA
      sensitization has increased as a result of the number of patients bridged to
      transplant using left ventricular assist devices (LVAD). Here we have examined
      119 patients who were bridged to transplant with LVAD for a relationship between
      HLA antibodies and early (30 days) and late (2 years or more) rejection, as
      evidenced by endomyocardial biopsies. Both cytotoxic panel-reactive antibody
      reactions against a panel of T lymphocytes (T-PRA) and the percentage of
      transplants that occurred across a positive class I flow cross-match were
      examined. Biopsies were scored using ISHLT criteria. At 30 days, patients who had
      a biopsy grade of 0 had a mean T-PRA at transplant of 2.2%, while the mean PRAs
      of the other biopsy grades were significantly higher (P < .001). A similar
      pattern was seen with the highest biopsy results at 2 years or later (P < .001).
      None of the patients who had a grade 0 biopsy at 30 days posttransplant had a
      positive flow cytometry class I cross-match (P = .02), although the same pattern
      did not occur later due to a small number of patients (n = 3) who had negative
      biopsies. Thus, when biopsy results were examined early or late posttransplant,
      patients with negative biopsy results tended to have less HLA sensitization.
      While the methods of HLA sensitization involve humoral responses, more aggressive
      immunosuppression might be warranted to attempt to reduce cellular rejection
      posttransplant if HLA class I antibodies are present at the time of transplant.

PMID- 15848718
TI  - Chronic renal failure and end-stage renal disease are associated with a high rate
      of mortality after heart transplantation.
AB  - The aim of the study was to analyze the etiology, the factors for progression of
      chronic renal failure to end-stage-renal disease (ESRD), and the influence of
      ESRD on the survival rate among a cohort of 59 heart transplant patients (HTP)
      referred for the management of chronic renal failure (CRF). At the time of the
      first nephrology consultation (6 +/- 4.25 years after cardiac transplantation)
      the mean creatininemia was 261.5 +/- 99 micromol/L and mean creatinine clearance
      (Cockcroft formula) was 32 +/- 15 mL/min. The cause of CRF were calcineurin
      inhibitor toxicity in 38.9% of patients, vascular events in 15.2%, hemolytic
      uremic syndrome in 5%, membranous glomerulopathy in 3.3%, diabetes in two
      patients, focal/segmental glomerulosclerosis in 3.3%, renal hypoplasia in 1.7%,
      and unknown in 27%. Evolution to ESRD occurred in 38.9% of patients: 17 patients
      started hemodialysis, three peritoneal dialysis, and two received a preemptive
      kidney transplantation. Creatininemia (micromol/L) at the time of nephrology
      referral was 229.2 +/- 72.6 versus 315.8 +/- 113.4 (P < .001) and creatinine
      clearance (mL/min) was 34.9 +/- 15.1 versus 27.3 +/- 13.7 (P = .049) for patients
      with CRF versus ESRD, respectively. Both proteinuria (g/24 hours) of 1 +/- 2.2
      versus 2.3 +/- 1.8 (P = .02) and tobacco use in 35.1% versus 54.4% (P = .045)
      were significantly associated with progression of CRF, while age at the time of
      heart transplantation, cause of cardiac failure and renal failure, high blood
      pressure, type 2 diabetes, dyslipidemia, alcoholism, cirrhosis, and cerebral
      vascular accident were not. Death occurred in 18 HTP: 50% of patients with ESRD
      and 18.5% of patients with CRF-a 2.6 relative risk of of death in HTP patients
      with ESRD compared with HTP with CRF only (P < .01).

PMID- 15848719
TI  - C2 and C0 values for monitoring cyclosporine therapy in stable heart transplant
      recipients.
AB  - INTRODUCTION: We sought to evaluate the behavior of C2 values and their
      correlation with acute rejection episodes and cyclosporine (CyA) side effects in
      heart transplant patients whose immunosuppressive therapy, was monitored with C0
      trough levels. METHODS: Sixty stable patients who had received heart transplants
      from 3 months to 60 months prior were randomly observed from September 2001 to
      June 2004. Four area under the concentration-time curves (AUC) were performed on
      each patient, a total of 240 AUC curves. RESULTS: Regarding the variability of
      CyA absorption, two groups of patients were distinguished: group A, "constant
      absorbers," namely, low variability (<15%) of CyA absorption; group B,
      "inconstant absorbers" patients with higher (>15%) variability of absorption.
      Group B patients showed more acute rejection episodes (41%) than group A (19%).
      CyA side effects were more serious in patients with higher variability of
      absorption: systemic hypertension, neurological disorders, hyperlipidemia, and
      gum hyperplasia; Group B patients who developed CyA side effects showed higher
      maximum and mean C2 levels (P < .05) than group A patients. No differences were
      found with regard to renal dysfunction between the two groups: all patients
      showed a mean increase of serum creatinine by at least 50% compared to the
      baseline value. CONCLUSION: Higher C2 levels were not sufficient to predict acute
      rejection compared to lower but constants, C2 levels. Patients with inconstant
      absorption were more often overexposed to CyA than underexposed, developing more
      side effects than patients with lower variability of absorption. Monitoring CyA
      therapy with C0 and C2 may prevent over- or underexposure to the drug.

PMID- 15848720
TI  - C0h/C2h monitoring of the pharmacodynamics of cyclosporin plus mycophenolate
      mofetil in human heart transplant recipients.
AB  - Pharmacokinetic (PK) parameters like C2h have improved efficacy of
      immunosuppressive therapy. However, drug interactions, toxicities, and individual
      differences to drug effects still remain challenging. Therefore, this study was
      designed to assess pharmacodynamic (PD) effects of the combination cyclosporin
      (CsA) plus mycophenolate mofetil (MMF) on lymphocyte functions in peripheral
      blood of stable heart transplant recipients (HTx) using our established FACS
      assays. METHODS: Blood from 25 HTx patients was drawn before (C0h) and 2 hours
      after dosing (C2h). CsA and mycophenolic acid (MPA) concentrations were measured
      by EMIT. FACS assessed expression of cytokine production (IL-2, TNF-alpha),
      lymphocyte proliferation (PCNA), and T-cell activation (CD25, CD95). RESULTS:
      Evening doses of CsA (25/50/75 or 100 mg) and MMF (250/500 or 1000 mg) produced
      C0h levels as follows: CsA, 162 +/- 12 ng/mL; MPA, 1.7 +/- 0.2 mg/L. Morning
      doses of CsA (50/75 or 100 mg) and MMF (250/500/1000 or 1500 mg) produced C2h
      levels as follows: CsA, 589 +/- 56 ng/mL and MPA, 7.4 +/- 1.3 mg/L. PD effects at
      C0h/C2h (% expression +/- SEM, all P < .05) were IL-2, 18 +/- 3/10 +/- 2; TNF
      alpha, 12 +/- 2/7 +/- 1; PCNA, 8 +/- 1/5 +/- 1; CD25, 26 +/- 4/13 +/- 2; CD95, 23
      +/- 4/11 +/- 2). Correlations (r2) at time point C2h between inhibition of
      lymphocyte functions (PD) with drug concentrations (PK) and with drug doses were
      CsA-PK, 0.71 to 0.91; MMF-PK, 0.55 to 0.76; CsA-dose, 0.73 to 0.87; MMF-dose,
      0.61 to 0.80. CONCLUSION: For the first time, the immunosuppressive effects of
      the combination CsA plus MMF were quantified in whole blood of human HTx at
      different time points. PD assays may offer the opportunity to optimize clinical
      immunosuppressive drug therapy.

PMID- 15848721
TI  - Primary cardiac lymphoma in a heart transplant recipient.
AB  - Posttransplantation lymphoproliferative disease (PTLD) is one of the most serious
      complications of chronic immunosuppression in transplant recipients. Involvement
      of the cardiac allograft or development of lymphoma in the heart is extremely
      rare. We report a primary cardiac lymphoma that developed about 14 months after
      the operation in a cardiac recipient. The patient presented with vague abdominal
      complaints. Multiorgan failure developed within a short period of time, and the
      patient died. The diagnosis of "diffuse large cell lymphoma of B cell type" was
      made on postmortem examination.

PMID- 15848722
TI  - Posttraumatic stress disorder after implantation of a mechanical assist device
      followed by heart transplantation: evaluation of patients and partners.
AB  - AIM: We sought to investigate the prevalence of posttraumatic stress disorder,
      anxiety, and depression in patients and their partners after implantation of a
      mechanical assist device as a bridge to heart transplantation. METHODS: This was
      a retrospective assessment of 41 patients (age 46.3 +/- 12.0 years; male-female
      ratio, 38:3; time since transplantation, 55.3 +/- 34.2 months [range, 7-122
      months) and 27 partners (male-female ratio 2:25) by standardized instruments
      (Impact of Event Scale, Hospital Anxiety and Depression Scale), in 2 University
      Heart Transplant Centers (Vienna, Austria, Munster, Germany). The duration of the
      support systems (MicroMed DeBakey-VAD in 17 patients, Novacor in 10, Thoratec in
      8, TCI HeartMate in 5, and Berlin Heart Incor in 1 patient) ranged from 28 to 711
      (176 +/- 146) days. RESULTS: None of the patients, but 23% of the partners (n =
      6), met the criteria for posttraumatic stress disorder (Maercker cutoff >0). The
      Impact of Event Scale (IES) sum scales differed significantly between the 2
      groups (21.2 +/- 15.1, mean +/- SD) for the patients versus 38.1 +/- 27.8 for the
      partners, respectively; P = .001). Two percent of the patients, but 19% of the
      partners, showed mild to moderate depression; 4% of patients, but 23% of their
      partners, reported mild to moderate anxiety. None of the results were
      significantly influenced by the time since transplantation, patient age,
      diagnoses, type of assist device, or indication for heart transplantation.
      CONCLUSIONS: Despite patients being much closer to a life threat, their partners
      experience significantly more psychologic distress even in the long run. Our
      findings highlight the need for attention to the supporting persons.

PMID- 15848723
TI  - Outcome following single vs bilateral lung transplantation in recipients 60 years
      of age and older.
AB  - AIMS: The significant shortage of donor organs in lung transplantation
      necessitates a careful selection of lung transplant recipients. The outcome of
      lung transplant recipients aged 60 years and older has not been analyzed
      systematically. METHODS: We retrospectively reviewed our experience with older
      recipients. Between January 1999 and July 2003, 248 patients underwent lung
      transplantation at our institution, of which 18 were aged 60 years and older
      (7.3%, range 60-66, mean 62 +/- 1.1). RESULTS: Eleven (61%) of the recipients 60
      years and older received a single (SLTx) and seven (39%), a bilateral lung
      transplant. Donor age in the single transplant cohort was 30 +/- 4 years. It was
      33 +/- 3 years in bilateral patients. Posttransplant ventilation time was
      significantly different among groups, with 282 +/- 32 hours after bilateral and
      56 +/- 13 hours after transplant (P < .05). Also significantly longer was the
      length of the ICU stay in the bilateral group. First PaO2 in the ICU was not
      different among the two groups. The 1-year survival in the single transplant
      group was significantly better compared to the bilateral group with 73% versus
      43%, respectively. CONCLUSIONS: The 1-year survival following lung
      transplantation in patients older than 60 years is markedly reduced compared to
      recipients under 60 years of age. If a lung transplant is considered in a
      recipient above the age of 60 years, a single transplant should be favoured. If
      that is not indicated, patients over 60 should be very carefully selected for
      bilateral transplant.

PMID- 15848724
TI  - Relationship between anti-ABO antibody production and hemolytic anemia after
      minor ABO-mismatched living-donor lobar lung transplantation.
AB  - With the shortage of lung donors, we have performed 28 living donor lobar lung
      transplantations (LDLLTs) since October 1998. Although lungs from ABO-identical
      donors were used if available, lungs were transplanted from donors showing minor
      ABO mismatches when suitable ABO-identical donors were not found. The aim of this
      study was to evaluate the relationship between anti-ABO antibody (Ab) production
      and the outcomes of lung transplantation with ABO-mismatched living donor lungs.
      We reviewed 28 patients (28 recipients with 55 donors) who underwent LDLLT
      between October 1998 and March 2004. In this patient population, 13 patients
      (46.4%) received minor ABO-mismatched transplants. Anti-A or B-IgG or IgM
      antibodies (Abs) in the serum and red cell elutes were examined. All 28 patients
      are alive and well at a mean observation period of 28.0 months (ranging from 5 to
      70 months). Anti-A or B-IgG or IgM Abs were detected in 5 out of 13 minor ABO
      mismatched patients (38.5%) after transplantation, but only one of them showed
      evidence of severe hemolytic anemia due to donor-derived antibodies. The titer of
      that patient's Abs was higher than that of the other recipients. Anti-ABO
      antibody production and anemia were not associated with gender, age, relationship
      between donors and recipients, and HLA matching. We conclude that LDLLT across
      ABO mismatches is an acceptable treatment for end-stage lung disease.

PMID- 15848725
TI  - Abrogation of the alloreactive responses of cadaveric donor intestinal
      lymphocytes by intraoperative Campath-1H exposure.
AB  - A number of recent reports in clinical and experimental intestinal
      transplantation have suggested that the donor lymphocytes present in and around
      the gastrointestinal system are potent mediators of graft-versus-host (GvH)
      reactivity and that GvH responses may contribute to posttransplant morbidity.
      Therefore, we have tested the proliferative and cytotoxic capabilities of gut
      associated lymphocytes from cadaveric donors obtained prerevascularization (pre
      r) and about 6 hours postrevascularization (post-r) in recipients pretreated with
      Campath-1H antibody (alemtuzumab). Mixed lymphocyte reactions (MLR) were
      performed with lymphoid cells isolated from intestinal epithelial mucosa, lamina
      propria, and lymph nodes. The pre-r lymphocytes responded strongly to both the
      recipient and third-party alloantigenic stimulating cells. However, similar
      preparations from the post-r samples responded in MLR at significantly lower
      levels (P < .01). This post-r decrease in responsiveness was not observed in
      similar lymphocyte samples obtained from donors of recipients not treated with
      Campath-1H. Both the pre-r and post-r samples had similar flow cytometric
      profiles, suggesting that there was no receptor loss in these lymphoid tissues by
      the short-term 6-hour exposure to Campath-1H given to the recipient. Conversely,
      in preliminary experiments where the donor were treated with Campath-1H, it was
      observed that very few lymphocytes could be obtained from intestinal tissues (n =
      3). These results suggested that Campath-1H treatment of the recipient could
      bring about a drastic reduction in an otherwise strong GvH reactivity by the
      donor intestinal immune cells.

PMID- 15848726
TI  - Transplantation for the treatment of intra-abdominal fibromatosis.
AB  - MATERIALS AND METHODS: During the last 9 years we treated 14 patients with a
      diagnosis of intra-abdominal fibromatosis. The 11 patients who received an
      intestinal allograft included isolated intestine (n = 6), liver-intestine (n =
      1), intestine-kidney (n = 1), multivisceral (n = 1), multivisceral-kidney (n =
      1), multivisceral-no liver (n = 1). Three patients received an intestinal
      autograft after partial abdominal evisceration and ex vivo tumor resection. Three
      patients additionally underwent an abdominal wall allograft. RESULTS: At follow
      up until August 2004, all autotransplant patients are alive. Four intestinal
      transplant patients died within the first postoperative month. There were three
      graft losses. A patient who lost his graft early postoperatively was
      retransplanted but died of sepsis shortly there after. Two more patients lost
      their graft due to severe rejection and were retransplanted successfully. Two
      patients developed desmoid tumor recurrence in their abdominal or thoracic wall.
      Ten patients are alive 1 to 9 years posttransplantation. Nine have fully
      functioning grafts and one patient requires TPN supplementation at night due to
      dysmotility of her autograft. CONCLUSION: Intestinal allo-, or
      autotransplantation combined with transplantation of the abdominal wall can be
      lifesaving for patients suffering from extensive intra-abdominal fibromatosis.

PMID- 15848727
TI  - Living-related small bowel transplantation: two cases experiences.
AB  - We have recently performed living-related small bowel transplantation for 2
      patients. The first patient was a 14-year-old boy with total parenteral nutrition
      (TPN)-dependent short-bowel syndrome associated with hypoganglionosis of the
      entire intestine. He received a bowel graft from his 43-year-old mother. The
      second patient was a 27-year-old woman, who had massive enterectomy due to
      volvulus and developed vitamin deficiencies and severe metabolic disorders as a
      result of long-term TPN. She underwent living-related bowel transplantation from
      her 57-year-old mother. Blood types were ABO identical, cytotoxic cross matches
      were negative, and cytomegalovirus statuses were positive-to-positive in both
      cases. Up to one third of the donor bowel was harvested from the donor distal
      ileum more than 30 cm away from the ileocecal valve. The graft vessels were
      connected to infrarenal aorta, and inferior vena cava. The immunosuppressive
      regimen consisted of daclizumab, tacrolimus, and steroid. The graft surveillance
      was accomplished using zoom endoscopy and mucosal biopsy. The first patient
      developed progressive acute cellular rejection (ACR) on the 9th postoperative day
      (POD)-9 requiring OKT-3 therapy, which was effective. Two months after
      transplantation, he was weaned from TPN, tolerating oral intake with a fully
      functioning graft. The second patient experienced no episode of ACR and was
      weaned off TPN on POD-29 with a functioning graft. Her metabolic disorder
      dramatically improved after bowel transplantation. Both donors had no
      complication and were discharged from the hospital on POD-10. Living-related
      bowel transplantation is an extreme option of treatment for patients with short
      bowel syndrome.

PMID- 15848728
TI  - Levels of anti-A/B antibodies after ABO-incompatible hematopoietic stem cell
      transplantation.
AB  - In contrast to solid organ transplantation, ABO incompatibility is generally not
      associated with survival differences in hematopoietic stem cell transplantation.
      Therefore, patients receiving ABO-incompatible stem cell transplantation can be
      analyzed to study the mechanism of tolerance induction after antigen-mismatched
      transplantation. The goal of this study was to analyze the levels of anti-A/B
      antibodies after ABO-incompatible transplantation. Host-derived antidonor
      antibodies disappeared rapidly after transplantation and did not reappear in the
      further posttransplant course. Donor-derived antihost antibodies did not
      significantly increase and compatible anti-A/B antibodies remained positive after
      hematopoietic stem cell transplantation. Thus, there is no evidence for
      stimulation of donor B lymphocytes to produce antirecipient antibodies suggesting
      a potential B cell tolerance.

PMID- 15848729
TI  - Evaluation of mixed chimerism in bone marrow transplantation program in Croatia.
AB  - In this study we monitored mixed chimerism in 36 patients with various
      hematologic disorders. All of them underwent a classic conditioning regimen, 31
      patients for related bone marrow transplantation (BMT) and 5 patients for
      unrelated BMT. DNA was isolated from peripheral blood, and samples were
      polymerase chain reaction (PCR) amplified for 5 short tandem repeat (STR) loci
      (TH01, VWA31, FES/FPS, F13A01, and SE33) and for one variable number of tandem
      repeats locus (D1S80). Samples were run on a 6% polyacrylamide gel in an
      automated ALFexpress sequencer. In all 36 donor-recipient pairs we found
      differences for at least two STR loci. In most cases the difference was observed
      for SE33 and D1S80 loci. Mixed chimerism (MC) was detected in 18 patients: 4 with
      unrelated BMT and 14 with related sibling donors. In 11 patients MC was detected
      in the early period after BMT, but was soon followed by full donor chimerism
      (FDC) in peripheral blood. In 5 cases patients MC appearing after FDC was
      established, and was predictive for the relapse. One patient showed alternating
      MC and FDC, but at the end showed only recipient cells and graft rejection. In
      conclusion, the PCR-STR analysis is a highly informative, fast, and simple
      screening method for monitoring chimerism in a BMT program.

PMID- 15848730
TI  - Ethical considerations in the early composite tissue allograft experience: a
      review of the Louisville Ethics Program.
AB  - This paper reviews the formulation and evolution of the ethical component in one
      of the earliest clinical composite tissue allograft (CTA) programs, the hand
      transplantation program in Louisville, Kentucky, USA. The purpose was to derive
      lessons and define principles to give guidance for future programs and
      introduction of new CTA. We reviewed the initial ethical considerations,
      including input from respected ethical scholars, guidelines for innovative
      procedures transparency in public and professional scrutiny, and compliance with
      human studies regulations (IRB approval). We found the initial focus on ethics,
      scholarly input, guidelines for innovative procedures, and human studies
      protection regulations to be valid. Moreover, we noted the effect of autonomy in
      subjective, quality-of-life benefits on equipoise and effective risk-benefit
      analysis in effective informed consent. We found that psychiatric screening and
      support to be exceptionally valuable in protecting autonomy, suitability for
      participation, assessing personality organization, and determining compliance
      ability. We conclude that the program ethical principles were validated. For
      future CTA programs and procedures, we recommend an ethical emphasis with
      adherence to high standards and transpire to independence to scrutiny and
      oversight. We recommend protection of autonomy judgments in equipoise judgment
      and informed consent. We recommend skilled psychiatric screening and support. We
      endorse scholarship, scientific accuracy, and data sharing.

PMID- 15848731
TI  - Ovarian transplant: a new frontier.
AB  - Two cases of orthotopic ovarian transplantations were performed on patients
      diagnosed to have Turner's syndrome (ovarian dysgenesis) with primary amenorrhea,
      short stature, and absent secondary sexual characters. Chromosomal analysis
      showed 45XO pattern. Both transplants were living related from a sister and from
      a mother. In both the cases the donor and the recipient were immunologically
      matched by blood group, histocompatibility antigens (HLA), and lymphocyte cross
      match done twice. The donor ovaries were dissected extraperitoneally to have long
      vascular pedicles. In the first case the donor ovarian vein was sutured end-to
      side to external iliac vein and the ovarian artery was sutured to the inferior
      epigastric artery end-to-end using an operative microscope. The ovary was placed
      in the orthotopic position transperitoneally. Follow-up for 2.5 years has shown
      regular menstruations, documented ovulations, rise in hormonal levels, and
      development of secondary sexual characters. In the second case there was no large
      vein available for anastomosis so that an avascular orthotopic transplantation
      was performed. The ovarian cortex was dissected in a fan-shaped manner of 0.5-cm
      strips. Two grafts sutured onto surgicel were placed orthotopically in the
      ovarian fossa and the remaining ones were placed into the broad ligament. One
      month follow-up shows good take-up and follicular development on USG, power
      angio, and MRI. Hormonal rise has indicated functioning graft. Immunosuppression
      was achieved in both cases using cyclosporine (4 mg/kg) and prednisolone (2
      mg/kg).

PMID- 15848732
TI  - A national study of burnout among American transplant surgeons.
AB  - This study examines burnout in a national sample of transplant surgeons. Data
      analyses were conducted on a sample of 209 actively practicing transplant
      surgeons. Measures included the Maslach Burnout Inventory, a demographic survey,
      and the Surgeon Coping Inventory. Burnout was reflected in 38% of surgeons
      scoring high on the Emotional Exhaustion dimension, whereas 27% showed high
      levels of Depersonalization, and 16% had low levels of Personal Accomplishment.
      Several significant predictors of emotional exhaustion were identified and
      included questioning one's career choice, giving up activities, and perceiving
      oneself as having limited control over the delivery of medical services (R2=
      0.43). Those who perceived themselves as having a higher ability to control
      delivery of medical services and who felt more appreciated by patients had lower
      levels of depersonalization and were less likely to question their career choice
      (R2= 0.16). Surgeons with high personal accomplishment experienced greater
      professional growth opportunities, perceived their institution as supportive,
      felt more appreciated by patients, and were less likely to question their career
      (R2= 0.24). The prioritization of goals to reflect both professional and personal
      values accounted for a significant amount of the variance in predicting both
      emotional exhaustion and personal accomplishment in separate regression
      equations. Recommendations to decrease burnout would include greater
      institutional support, increased opportunities for professional growth, and
      greater surgeon control over important services to facilitate efficient work.
      Coping strategies to moderate stress and burnout are also beneficial and should
      include prioritizing goals to reflect both professional and personal values.

PMID- 15848734
TI  - History of the development of the classification of renal cell neoplasia.
AB  - This article reviews the history of the development of the classification of
      renal cell neoplasia.

PMID- 15848735
TI  - The usefulness of immunohistochemical markers in the differential diagnosis of
      renal neoplasms.
AB  - Histologic subtyping of RCC has been shown to be of prognostic value; therefore,
      it is important to classify malignant epithelial tumors of the kidney correctly
      and also to differentiate them from benign ones. Overlapping morphologic features
      of renal tumors sometimes make histologic subtyping difficult. The accurate
      diagnosis and classification of RCC are based on cytoarchitectural features and
      require correlation with immunophenotype and cytogenetic characteristics. RCC Ma
      and CD10, two markers with relative renal specificity, have been used to confirm
      a diagnosis of suspected RCC and can facilitate the accurate diagnosis of
      metastatic RCC, in particular, in FNA. Although CCRCC and PRCC share most
      immunomarkers, CK7 and AMACR expression can be helpful in the differential
      diagnosis of challenging histologic variants of the two. In addition, E-cadherin
      aids in the distinction between types 1 and 2 PRCC. Useful markers in the
      differential diagnosis between ChRCC and CCRCCare CK7, RCC Ma, CD10, VIM, CD117,
      parvalbumin, and E-cadherin. We propose CK7/CK20/CD15 as a useful primary
      immunopanel to differentiate ChRCC from ONC reliably.

PMID- 15848736
TI  - Molecular genetics of familial renal cell carcinoma syndromes.
AB  - RCC represents a group of clinically and genetically diverse diseases. Familial
      RCC syndromes, although rare, provide an invaluable model to study the molecular
      mechanisms of renal carcinogenesis. Many causative oncogenes and tumor suppressor
      genes have been identified and it is now possible to identify the affected
      individuals and carriers by genetic testing. Understanding of the molecular
      pathways of these genes will have a significant impact on the diagnosis and
      treatment of familial and sporadic RCC.

PMID- 15848737
TI  - Application of molecular diagnostic techniques to renal epithelial neoplasms.
AB  - The application of molecular and cytogenetic techniques to the study of renal
      neoplasia has resulted in improved understanding of the biologic mechanisms that
      are responsible for tumor development and progression. It also revealed that
      several different and specific genetic events are responsible for tumorigenesis
      in the various categories and subcategories of renal tumors. The ultimate goal of
      research on the molecular pathology of renal neoplasms is a complete
      understanding of the genetics of these tumors, which will, in turn, aid in making
      the correct diagnosis, accurately assessing prognosis, and selecting appropriate
      and targeted therapeutic options.

PMID- 15848738
TI  - Clear cell renal cell carcinoma.
AB  - Clear cell RCC is the most common type of RCC that occurs in adults. It has the
      worst prognosis among the common epithelial tumors of the kidney. Histologically,
      a wide range of morphologic patterns can be encountered. Those cases with a multi
      locular cystic architecture are considered to be a distinct subtype because of
      the clinicopathologic features.

PMID- 15848739
TI  - Oncocytic renal neoplasms: diagnostic considerations.
AB  - Advances in our understanding of renal neoplasia have resulted in recognition of
      numerous tumors that are composed predominantly of cells with abundant
      eosinophilic cytoplasm. This article discusses the features of renal oncocytoma
      (including oncocytosis), chromophobe renal cell carcinoma (RCC), and clear cell
      RCC; explores the relationship between renal oncocytoma and chromophobe RCC;
      briefly discusses other tumors with abundant eosinophilic cytoplasm; and
      emphasizes the differential diagnosis of such tumors.

PMID- 15848740
TI  - Nephroblastic neoplasms.
AB  - Nephroblastoma, or Wilms tumor, is a malignant embryonal neoplasm that is derived
      from nephrogenic blastemal cells, with variable recapitulation of renal
      embryogenesis. The pathogenesis of nephroblastoma is complex and has been linked
      to alterations of several genomic loci, including WT1, WT2, FWT1, and FWT2.
      Generally, nephroblastoma is composed of variable proportions of blastema,
      epithelium, and stroma, each of which may exhibit a wide spectrum of morphologic
      variations. Distinguishing nephroblastoma with favorable histology from tumors
      that exhibit anaplasia is an integral component of histologic assessment because
      of its prognostic and therapeutic implications. Nephrogenic rests and a special
      variant of nephroblastoma, cystic partially differentiated nephroblastoma, also
      are discussed.

PMID- 15848741
TI  - Translocation carcinomas of the kidney.
AB  - A significant proportion of RCCs of children and young adults bear specific
      chromosome translocations that result in gene fusions that involve members of the
      MiTF/TFE transcription factor family. These include the Xp11-translocation
      carcinomas, which bear TFE3 gene fusions, and the renal carcinomas with the
      t(6;11)(p21;q12), which bear an Alpha-TFEB gene fusion. Both types of
      translocation result in overexpression of the fusion gene products, such that
      nuclear labeling for TFE3 or TFEB by immunohistochemistry is a sensitive and
      specific marker of these respective tumor types. The clinical behavior of these
      neoplasms relative to conventional, adult-type renal carcinomas remains to be
      determined, and will be an important area of future investigation.

PMID- 15848742
TI  - Metanephric neoplasms: the hyperdifferentiated, benign end of the Wilms tumor
      spectrum?
AB  - Metanephric neoplasms represent a spectrum of differentiated lesions that seem
      most likely to be related to Wilms tumor. These neoplasms include a pure stromal
      lesion, a pure epithelial lesion (MA), and a mixed epithelial-stromal lesion
      (MAF). The continuity of these lesions with Wilms tumor has been demonstrated
      best in the epithelial lesions. The relationship of Wilms tumor, MAF with mitoses
      or combined MA/Wilms tumor lesions, and usual MAF or usual MA may be viewed as
      analogous to that of neuroblastoma, differentiating neuroblastoma, and
      ganglioneuroma, in which progressively more mature or differentiated counterparts
      of malignant embryonal lesions are associated with a greater probability of
      benign clinical behavior. Such a spectrum already is recognized for cystic ILNR
      derived nephroblastic lesions, ranging from cystic Wilms tumor, cystic partially
      differentiated nephroblastoma, and cystic nephroma. Although this concept implies
      that the more active lesions (Wilms tumor) mature with time into inactive ones
      (usual MAFs or MA), the converse (that an active Wilms tumor can arise within an
      inactive usual MAF or MA) remains possible.

PMID- 15848743
TI  - Tubulocystic carcinoma, mucinous tubular and spindle cell carcinoma, and other
      recently described rare renal tumors.
AB  - In the past 10 years, several new renal tumors have been identified. Some have
      been reviewed in this article, and others have been reviewed elsewhere in this
      issue. Most have been included in the 2004 edition of the WHO classification of
      tumors of the urinary system and male genital organs. Tubulocystic carcinoma
      needs to be studied and characterized more fully.

PMID- 15848744
TI  - Handling and reporting of tumor-containing kidney specimens.
AB  - The pathologic features of RCC are the most valuable factors in predicting the
      prognosis and for planning surveillance and treatment protocols. Urologists and
      pathologists should optimize approaches in handling tumor-containing kidney
      specimens to allow for the best evaluation and reporting of such specimens. A
      pathologic report of a tumor-containing kidney specimen should include all
      established or potential prognostic factors, especially tumor types, size, grade,
      information for pathologic staging, and status of the surgical margin.

PMID- 15848745
TI  - A review of prognostic pathologic features and algorithms for patients treated
      surgically for renal cell carcinoma.
AB  - Accurate subtyping of RCC is critically important and should be considered in
      algorithms that are developed as prognostic tools for the patient and clinician.
      The TNM classification, already a powerful prognostic factor, will continue to
      evolve. The authors recommend that each component of the classification be
      assessed and reported during pathologic examination. This article also
      highlighted the importance of assigning a nuclear grade that is based on
      standardized and reproducible criteria that reflect the heterogeneity of nuclear
      and nucleolar features within RCC. Lastly, it is increasingly evident that
      coagulative tumor necrosis and sarcomatoid differentiation are compelling
      prognostic factors, on par with nuclear grade, and should be assessed routinely.
      To conclude, the complete list of pathologic features that are evaluated as part
      of the Mayo Clinic Nephrectomy Registry is presented. The features that are
      reported routinely in clinical practice also are indicated; this can serve as a
      guide for the reporting of results from the pathologic examination of RCC.

PMID- 15848746
TI  - Volsurf analysis of carbapenem antibiotics.
AB  - Classical Volsurf approach was applied to a set of 70 carbapenem compounds acting
      as antibiotics. Antibacterial activity of Staphylococcus aureus SG 511 and
      Escherichia coli 078 representing Gram positive and Gram negative bacteria,
      respectively, was used for the analysis. The score plots obtained from principal
      component analysis showed clustering of compounds according to the activity and
      their loading plots explained the Volsurf descriptors responsible for the
      separation or peculiar behaviour of these compounds. Partial Least Square
      analysis yielded a seven component model for S. aureus with a cross-validated r2
      (q2) value of 0.684 and conventional r2 value of 0.883 and for E. coli it is a
      six component model with cross-validated r2 (q2) value of 0.514 and conventional
      r2 value of 0.756. Both the PCA and PLS models were validated by an external test
      set of 15 compounds. All the compounds of the test set were fairly predicted with
      residual values less than one log unit. Comparatively activity data of S. aureus
      (Gram positive) was better explained than E. coli (Gram negative) by these
      models.

PMID- 15848747
TI  - Biotin-labeled abscisic acid as a probe for investigating abscisic acid binding
      sites on plasma membranes of barley aleurone protoplasts.
AB  - Plant hormone abscisic acid (ABA) plays important roles in dormancy and stress
      responses, but its binding sites have not yet been fully elucidated. In this
      report, we suggest the utility of biotin-labeled abscisic acid (bioABA) as a
      probe to investigate ABA-binding sites on the plasma membrane of barley aleurone
      protoplasts. BioABA was approximately 100 times less effective than ABA in
      inhibiting expression of gibberellin-inducible alpha-amylase and in inducing
      expression of a reporter gene fused to the dehydrin promoter. To ascertain that
      bioABA could bind to ABA-binding sites on the plasma membrane, we used
      fluorescence flow cytometry to measure the fluorescence intensity of aleurone
      protoplasts treated with a combination of bioABA and fluorescence-labeled
      streptavidin. Addition of bioABA increased the fluorescence of aleurone
      protoplasts in a concentration-dependent manner, but addition of non-active
      bioABA derivatives did not. Furthermore, the increase in fluorescence intensity
      observed upon addition of bioABA was eliminated by co-treatment with excess ABA,
      but it was not eliminated by co-treatment with other plant hormones. These
      results suggest that bioABA binds to ABA-binding sites, and that bioABA should be
      a valuable probe for investigating ABA-binding sites on the plasma membrane.

PMID- 15848748
TI  - Differences between the structural requirements for ABA 8'-hydroxylase inhibition
      and for ABA activity.
AB  - A major catabolic enzyme of the plant hormone abscisic acid (ABA) is the
      cytochrome P450 monooxygenase ABA 8'-hydroxylase. For designing a specific
      inhibitor of this enzyme, the substrate specificity and inhibition of CYP707A3,
      an ABA 8'-hydroxylase from Arabidopsis thaliana, was investigated using 45
      structural analogues of ABA and compared to the structural requirements for ABA
      activity. Substrate recognition by the enzyme strictly required the 6'-methyl
      groups (C-8' and C-9'), which were unnecessary for ABA activity, whereas
      elimination of the 3-methyl (C-6) and 1'-hydroxyl groups, which significantly
      affected ABA activity, had little effect on the ability of analogues to
      competitively inhibit the enzyme. Fluorination at C-8' and C-9' resulted in
      resistance to 8'-hydroxylation and competitive inhibition of the enzyme. In
      particular, 8',8'-difluoro-ABA and 9',9'-difluoro-ABA yielded no enzyme reaction
      products and strongly inhibited the enzyme (K(I) = 0.16 and 0.25 microM,
      respectively).

PMID- 15848749
TI  - Biocatalysed synthesis of beta-O-glucosides from 9-fluorenon-2
      carbohydroxyesters. Part 3: IFN-inducing and anti-HSV-2 properties.
AB  - In pursuing research on the antiviral, interferon (IFN)-inducing tilorone
      congeners, a new series of fluoren-carboxyhydroxyesters has been prepared and
      biologically explored. These esters have subsequently been used as sugar
      acceptors in the enzymatic transglycosylation reaction using the 'retaining' beta
      glycosidase from the archaeon Sulfolobus solfataricus (Ssbeta-Gly). Both
      aglycones (1-6) and corresponding beta-glucosides (beta-glu 1-beta-glu 6) have
      been screened for cytotoxicity, interferon-stimulating and antiviral properties
      against HSV-2. It was found that the addition of compounds beta-glu 5, beta-glu 6
      and beta-glu 4 to HSV-2 infected U937 cells downregulates viral replication and
      triggers cells to release IFN-alpha/beta. Taken together, the results showed
      improved pharmacological profiles as a consequence of glycosylation. A molecular
      modelling study carried out on this series of compounds completed the structural
      characterisation of the novel compounds.

PMID- 15848750
TI  - Position-specific incorporation of a highly photodurable and blue-laser excitable
      fluorescent amino acid into proteins for fluorescence sensing.
AB  - A new fluorescent amino acid, L-2-acridonylalanine, was incorporated into
      proteins at specific positions using 4-base codon/anticodon strategy. The
      efficiency of the incorporation was high enough to obtain enough quantities of
      the mutants. The acridonyl group was highly fluorescent when it was excited at
      the wavelengths of blue-lasers and was highly photodurable compared with
      conventional fluorophores often used for biological analyses. The fluorescence
      intensity was sensitive to small changes in the polarity of the environment. When
      the nonnatural amino acid was incorporated into specific positions of
      streptavidin, the mutant protein worked as a fluorescent sensor to biotin.
      Similarly, when the amino acid was incorporated into camel single-chain antibody,
      the mutant protein sensitively responded to the antigen molecule. The high
      incorporation efficiency, the high photodurability, the excitability with blue
      lasers, and high sensitivity to the environment make the acridonylalanine as the
      promising fluorescent amino acid for sensing small molecules when incorporated
      into specific positions of various antibodies, receptors, and enzymes.

PMID- 15848751
TI  - Linear indices of the 'macromolecular graph's nucleotides adjacency matrix' as a
      promising approach for bioinformatics studies. Part 1: prediction of
      paromomycin's affinity constant with HIV-1 psi-RNA packaging region.
AB  - The design of novel anti-HIV compounds has now become a crucial area for
      scientists around the world. In this paper a new set of macromolecular
      descriptors (that are calculated from the macromolecular graph's nucleotide
      adjacency matrix) of relevance to nucleic acid QSAR/QSPR studies, nucleic acids'
      linear indices. A study of the interaction of the antibiotic Paromomycin with the
      packaging region of the HIV-1 psi-RNA has been performed as example of this
      approach. A multiple linear regression model predicted the local binding affinity
      constants [Log K (10(-4) M(-1))] between a specific nucleotide and the
      aforementioned antibiotic. The linear model explains more than 87% of the
      variance of the experimental Log K (R = 0.93 and s = 0.102 x 10(-4) M(-1)) and
      leave-one-out press statistics evidenced its predictive ability (q2 = 0.82 and
      s(cv) = 0.108 x 10(-4) M(-1)). The comparison with other approaches
      (macromolecular quadratic indices, Markovian Negentropies and 'stochastic'
      spectral moments) reveals a good behavior of our method.

PMID- 15848752
TI  - Electrophilicity as a possible descriptor for toxicity prediction.
AB  - Electrophilicity is one of the cardinal chemical reactivity descriptors
      successfully employed in various molecular reactivity studies within a structure
      activity relationship parlance. The applications of this quantity in the modeling
      of toxicological properties have inspired us to perform a more exhaustive study
      in order to test and/or to validate the application of electrophilicity in
      assessing its chemical and toxicological potential. For this reason the toxicity
      of a large data set of molecules comprising 252 aliphatic compounds on the
      Tetrahymena pyriformis is studied. A quantitative structure-activity relationship
      analysis enabled us to model toxicity in terms of global and local
      electrophilicities, which provide a reasonably good prediction of aliphatic
      toxicity. It is heartening to note that the global and local electrophilicity
      values together can explain the toxicity of a large variety of aliphatic
      compounds nicely without resorting to any other descriptor or other
      microscopic/macroscopic physicochemical properties as is the situation in all
      other QSAR studies.

PMID- 15848753
TI  - Synthesis and antiprotozoan evaluation of new alkyl-linked bis(2-thioxo
      [1,3,5]thiadiazinan-3-yl) carboxylic acids.
AB  - Two new series of several alkyl-linked bis(2-thioxo-[1,3,5]thiadiazinan-3-yl)
      carboxylic acids were synthesized in a two step procedure from the corresponding
      alkyl bis-dithiocarbamic salt intermediary. The novel compounds were evaluated
      for their activity in vitro against Trypanosoma cruzi strain CL (clone CL B5) and
      Trichomonas vaginalis strain JH 31A.

PMID- 15848754
TI  - 1,4-Dihydropyridine derivatives as calcium channel modulators: the role of 3
      methoxy-flavone moiety.
AB  - It was earlier recognized that calcium antagonists, and in particular 1,4
      dihydropyridines, exhibited distinct cardiovascular profiles. In addition two
      different splice variants of the L-type calcium channel were found in vascular
      and cardiac tissues. In this study, novel substituted 1,4-dihydropyridines with a
      3-methoxy-flavone moiety were synthesized and structural modifications of the
      substituents in the dihydropyridine ring of nifedipine were carried out in order
      to find tissue specific compounds. The negative inotropic, chronotropic and
      vasorelaxant effects were investigated on guinea-pig left, right atria and aortic
      strips, respectively. The introduction of an heteroaromatic ring in 4-position of
      the 1,4-dihydropyridine nucleus led to compounds selective for cardiac tissues.
      Moreover, different residues in the 1,4-dihydropyridine ring could modulate the
      chronotropic versus inotropic activity.

PMID- 15848755
TI  - Synthesis and vasodilatory activity of new N-acylhydrazone derivatives, designed
      as LASSBio-294 analogues.
AB  - Conventional therapy to treat hypertension often involves arterial vasodilation.
      Decrease of blood pressure by vasodilators is normally associated with adverse
      effects because of their low vascular selectivity. This is of interest to develop
      new molecules with potential for clinical use and fewer side effects. Recently, a
      new bioactive compound of the N-acylhydrazone class, LASSBio-294, was shown to
      produce a cardioinotropic effect and vasodilation. In this report, new
      derivatives of LASSBio-294 were designed and tested on the contractile response
      of vascular smooth muscle from Wistar rats. Phenylephrine-induced contracture in
      the aorta was inhibited by the derivatives LASSBio-785 and LASSBio-788. The
      concentrations necessary to cause 50% reduction of the maximal vascular response
      (IC50) were 10.2 +/- 0.5 and 67.9 +/- 6.5 microM. Vasodilation induced by both
      derivatives is likely to be mediated by a direct effect on smooth muscle because
      it was not dependent on the integrity of vascular endothelium. LASSBio-785 was
      seven times more potent than the reference compound LASSBio-294 (IC50 = 74
      microM) in producing an endothelium-independent vasodilator effect.

PMID- 15848756
TI  - Design, synthesis and cytotoxic effect of hydroxy- and 3-alkylaminopropoxy-9,10
      anthraquinone derivatives.
AB  - In previous paper, we have reported the synthesis and the cytotoxic effect of 1,3
      dihydroxy-9,10-anthraquinone derivatives. For further design of more potent
      compounds, a new series of 1-hydroxy-3-(3-alkylaminopropoxy)-9,10-anthraquinones
      and 3-(3-alkylaminopropoxy)-9,10-anthraquinones have been synthesized. The
      cytotoxicity of synthetic compounds were evaluated against human Hep G2, Hep 3B
      and HT-29 cells. Almost all compounds indicated significant inhibitory activity
      against Hep G2, Hep 3B and HT-29 cell lines in vitro. Compound 5 exhibited
      selective cytotoxicity against Hep G2 in a concentration-dependent manner with
      ED50 value of 1.23 +/- 0.05 microM. Structure-activity analysis revealed that
      most of the 1-hydroxy-3-(3-alkylamino-2-hydroxypropoxy)-9,10-anthraquinone showed
      stronger cytotoxic effects than those of 1-hydroxy-3- or 3-(3-alkylaminopropoxy)
      9,10-anthraquinones against Hep 3B cell line in vitro. A sub-G1 cell stage and
      DNA fragmentation in MCF-7 cells were significantly observed after 72 h
      incubation with selective compound 16. The results show that 16 causes cell death
      by apoptosis.

PMID- 15848757
TI  - Synthesis of phthalates of betulinic acid and betulin with cytotoxic activity.
AB  - Synthesis of 3beta-O-phthalic esters from betulinic acid and its esters and
      synthesis of phthalic esters from betulin and its monoacetates using classical
      acylation procedure with phthalic anhydride. The evaluation of cytotoxicity of
      the prepared compounds was using numbers of tumor cell lines in MTT test. It was
      discovered that hemiphthalic esters had better cytotoxicity than starting
      compounds as betulinic acid or quite inactive betulin.

PMID- 15848758
TI  - Structure-affinity relationship studies on arylpiperazine derivatives related to
      quipazine as serotonin transporter ligands. Molecular basis of the selectivity
      SERT/5HT3 receptor.
AB  - A series of quipazine derivatives, previously synthesized to probe the 5-HT(3)
      receptor, was evaluated for its potential interaction with serotonin transporter
      (SERT). Some of them show nanomolar affinity for the rodent SERT comparable to or
      slightly higher than quipazine or N-methylquipazine. Subsequently a candidate was
      selected on the basis of its SERT affinity and submitted to a molecular
      manipulation of the basic moiety. The structure-affinity relationships obtained
      provided information on the role of the fused benzene ring of quipazine in the
      interaction with the SERT binding site and on the stereoelectronic requirements
      for the interaction of both the heteroaromatic component and the basic moiety.
      Moreover, the comparison of the structure-affinity relationships obtained in the
      present work with those concerning the interaction of these heteroarylpiperazine
      derivatives with 5-HT3 receptor suggested some molecular determinants of the
      selectivity SERT/5HT3 receptor.

PMID- 15848759
TI  - Synthesis of DEHP metabolites as biomarkers for GC-MS evaluation of phthalates as
      endocrine disrupters.
AB  - Phthalates are used primarily as plasticizers to make polyvinyl chloride (PVC)
      soft and flexible. In recent years the phthalate esters have attracted increasing
      attention as environmental and biomedical pollutants and, because of their
      toxicological characteristics. In particular, they are more and more recognized
      as endocrine disrupters. In this context, we describe herein an efficient
      synthetic pathway leading to a series of metabolites of di(2-ethylhexyl)
      phthalate (DEHP). Mono(2-ethylhexenyl) phthalate was used as starting material to
      obtain these products in good yield, large scale and GC-MS purity. The
      metabolites of DEHP were synthesized, for the first time, as biomarkers to verify
      their quantitative determination in human urine and serum by GC-MS analysis for
      studying the exposure to phthalates and establishing reference values.

PMID- 15848760
TI  - An efficient preparation of polyanionic affinity agent and its evaluation for the
      measurement of glycated hemoglobin.
AB  - An efficient method was developed for the preparation of polyanionic affinity
      agent (3), a key component in the measurement of glycated hemoglobin (GHb).
      Glycated hemoglobin is an important clinical marker for diagnosis of patients
      with diabetes and useful to monitor the management of disease. The affinity agent
      (3) was prepared based on coupling reaction between poly(acrylic acid) (1) and 3
      aminophenylboronic acid (2) in water. The critical features of this polymeric
      affinity agent (3), such as size, boronic acid incorporation ratio and
      concentration, on the measurement of glycated hemoglobin were evaluated. It was
      found that the agent (3) prepared using poly(acrylic acid) (1) with 225 kDa
      molecular weight gave optimal GHb measurement. The performance test results
      demonstrated that the boronic acid incorporation ratio and concentration of
      affinity agent (3) play a critical role in the assay and determines the precision
      of glycated hemoglobin measurement.

PMID- 15848761
TI  - Synthesis and evaluation of sphingoid analogs as inhibitors of sphingosine
      kinases.
AB  - Sphingosine 1-phosphate (S1P), a product of sphingosine kinases (SphK), mediates
      diverse biological processes such as cell differentiation, proliferation,
      motility, and apoptosis. In an effort to search and identify specific inhibitors
      of human SphK, the inhibitory effects of synthetic sphingoid analogs on kinase
      activity were examined. Among the analogs tested, we found two, SG12 and SG14,
      that have specific inhibitory effects on hSphK2. N,N-Dimethylsphingosine (DMS), a
      well-known SphK inhibitor, displayed inhibitory effects for both SphK1 and SphK2,
      as well as protein kinase C. In contrast, SG12 and SG14 exhibited selective
      inhibitory effects on hSphK2. Furthermore, SG14 did not affect PKC. In isolated
      platelets, SG14 blocked the conversion of sphingosine into sphingosine 1
      phosphate significantly. This is the first report on the identification of a
      hSphK2-specific inhibitor, which may provide a useful tool for studying the
      biological functions of hSphK2.

PMID- 15848762
TI  - Mutation of surface cysteine 374 to alanine in monoamine oxidase A alters
      substrate turnover and inactivation by cyclopropylamines.
AB  - Modification of cysteine (Cys) residues inactivates monoamine oxidases (MAO) yet
      the crystal structure shows no conserved cysteines in the active site of MAO A
      (Ma, J. et al. J. Mol. Biol.2004, 338, 103-114). MAO A cysteine 374 was mutated
      to alanine and the purified enzyme characterized kinetically. The mutant was
      active but had decreased k(cat)/K(m) values compared to the wild-type enzyme.
      Cyclopropylamine-containing mechanism-based inactivators similarly showed lower
      turnover rates. Spectral studies and measurement of free thiols established that
      1-phenylcyclopropylamine (1-PCPA) formed an irreversible flavin adduct whereas 2
      phenylcyclopropylamine (2-PCPA) and N-cyclo-alpha-methylbenzylamine (N-CalphaMBA)
      formed adducts that allowed reoxidation of the flavin on denaturation and
      decreased cysteine in both wild-type and mutant MAO A. In the 1-PCPA and N
      CalphaMBA inactivations, the partition ratio was decreased by more than 50% in
      the mutant. The data suggest that mutation of Cys374 influences MAO A catalysis,
      which has implications for MAO susceptibility to redox damage. These results are
      compared with previous work on the equivalent residue in MAO B, namely, cysteine
      365.

PMID- 15848763
TI  - Two novel series of allocolchicinoids with modified seven membered B-rings:
      design, synthesis, inhibition of tubulin assembly and cytotoxicity.
AB  - Two new attractive series of allocolchicinoids were designed as inhibitors of
      tubulin assembly using the potent ketone 4 and the tetracyclic, pyrazole
      annulated NCME variant 7 (NCME = N-acetyl colchinol-O-methylether (2)) as lead
      structures. The first group of inhibitors of type 6 with novel oxepine and
      azepine B-ring structures belongs to the NCME-series and was synthesized via a
      multistep total synthesis starting from simple and cheap 3-methoxybenzaldehyde
      (12) and 3,4,5-trimethoxybenzaldehyde (13). Biaryl-coupling of the starting
      materials 12 and 13 was accomplished via Ziegler-Ullmann-reaction to furnish the
      biphenyl 11 equipped with two carbaldehyde functions. The subsequent Cannizzaro
      reaction of this dicarbaldehyde 11 proceeded with high regioselectivity to yield
      almost exclusively the key compound, the hydroxymethyl carboxylic acid 9. Ring
      closure to the o,o'-bridged biphenyls was accomplished by two routes: on the one
      hand, treatment of 9 with aqueous hydrochloric acid yielded the lactone 15. On
      the other hand, a four step sequence starting from the isomeric mixture 9/10
      furnished the constitutionally isomeric lactams 23 and 24; these could be
      converted to the corresponding thiolactams 25 and 26 and to the tetrazole
      annulated NCME-type derivatives 27 and 28. The second series of bioactive
      compounds are congeners of allocolchicine (3). The well known desacetyl
      allocolchicine (29) was easily oxidized to the oxime 30, which was further
      transformed to the corresponding ketone 31. This served as key precursor for the
      syntheses of various tetracyclic allocolchicine modifications 33-36 annulated
      with a pyrazole, isoxazole, pyrimidine or 2-aminopyrimidine heterocycle,
      respectively. Unexpectedly, all the NCME-variants with a substituent in position
      7 like in NCME (2) inhibited the tubulin assembly only moderately. In contrast,
      the new series of allocolchicine modifications proved to be highly potent
      antimicrotubule agents. Inhibition of tubulin assembly occurred at lower
      concentrations compared to those measured for the reference colchicine (1).
      Surprisingly, these promising results could not be confirmed in the cytotoxicity
      tests against the human MCF-7 breast cancer cell line, where an unexpected loss
      of effectiveness compared to the corresponding NCME-derivatives was observed.

PMID- 15848764
TI  - Syntheses of novel heterocycles as anticancer agents.
AB  - Several pteridine analogues 4-13, 23-26 have been synthesized and tested in vitro
      against three cancer cell lines, MCF7 (breast), NCI-H460 (lung) and SF-268 (CNS).
      All tested pteridines can serve as novel templates for the anticancer
      chemotherapy and can serve as new leads in cancer chemotherapy.

PMID- 15848765
TI  - Biphenylquinuclidines as inhibitors of squalene synthase and growth of parasitic
      protozoa.
AB  - In this paper we describe the preparation of some biphenylquinuclidine
      derivatives and their evaluation as inhibitors of squalene synthase in order to
      explore their potential in the treatment of the parasitic diseases leishmaniasis
      and Chagas disease. The compounds were screened against recombinant Leishmania
      major squalene synthase and against Leishmania mexicana promastigotes, Leishmania
      donovani intracellular amastigotes and Trypanosoma cruzi intracellular
      amastigotes. Compounds that inhibited the enzyme, also reduced the levels of
      steroids and caused growth inhibition of L. mexicana promastigotes. However there
      was a lower correlation between inhibition of the enzyme and growth inhibition of
      the intracellular parasites, possibly due to delivery problems. Some compounds
      also showed growth inhibition of T. brucei rhodesiense trypomastigotes, although
      in this case alternative modes of action other than inhibition of SQS are
      probably involved.

PMID- 15848766
TI  - Novel anellated pyrazoloquinolin-3-ones: synthesis and in vitro BZR activity.
AB  - A series of pyrazolo[4,3-c]pyrrolo[3,2-f]quinolin-3-one derivatives 6, 7a-c,
      8a,b, 9a,b and 10-12 were synthesized as modified pyrazoloquinolinone analogs
      (PQs) and evaluated for their ability to inhibit radioligand to central and
      peripheral benzodiazepine receptors (BZRs) and their effect on GABA(A)
      alpha1beta2gamma2L receptors expressed in Xenopus laevis oocytes. Multistep
      synthesis starting from 5-nitroindole, via the Gould-Jacobs reaction to the
      quinoline nucleus, yielded key intermediates 9-chloro-3H-pyrrolo[3,2-f]quinoline
      8-carboxylates. The reaction of the latter with methyl-hydrazine and various
      phenyl-hydrazines furnished the final compounds. In order to confirm the expected
      tetracyclic 2-substituted-2H-pyrazolopyrroloquinolin-3-one structure, IR
      spectrophotometric, mono-1H and 13C and bi-dimensional spectrometric and HRMS
      analyses were carried out: all compounds were found to be 2-substituted 3-keto
      tautomers; compound 6 only differed because it turned out to be 1-methyl-2H
      pyrazolo[4,3-c]pyrrolo[3,2-f]quinolin-3-olo. The results of this work are
      consistent with those previously reported for PQs: 7-9 show high potency in
      displacing specific [3H]flunitrazepam from its receptor site; no compound was
      active in inhibiting the binding of [3H]PK 11195. They all act as antagonists at
      central BZR.

PMID- 15848767
TI  - Horseradish peroxidase-mediated aerobic and anaerobic oxidations of 3
      alkylindoles.
AB  - Little is known about the HRP-mediated oxidations of 3-alkylindoles. Whereas 3
      methylindole and 3-ethylindole were found to be turned over smoothly by HRP,
      reactions of tryptophol and N-acetyltryptamine were inefficient. Oxidations of
      the former two indoles by HRP under aerobic conditions led to the corresponding
      ring-opened o-acylformanilides and oxindoles, whereas anaerobic oxidations
      resulted in oxidative dimerization. The major products of anaerobic oxidation of
      3-methylindole were shown to be two hydrated dimers, while anhydrodimers were
      obtained in the 3-ethyl case. The proposed mechanism involves HRP-mediated one
      electron oxidation to give an indole radical that either dimerizes (anaerobic
      conditions) or reacts with O2 (aerobic conditions). Measured kinetics of indole
      oxidation by HRP compounds I and II mirrored their relative reactivities under
      turnover conditions. The observed comparable binding affinities for all four
      indole substrates investigated suggest that the low reactivity of tryptophol and
      N-acetyltryptamine reflect binding to HRP in an orientation that is
      disadvantageous to electron transfer oxidation of the indole ring.

PMID- 15848768
TI  - Synthesis and antibody-binding studies of a series of parasite fuco
      oligosaccharides.
AB  - Complex multifucosylated oligosaccharides are structural elements of glycoprotein
      and glycolipid subsets of larval, egg, and adult stages of Schistosoma, the
      parasitic worms that cause schistosomiasis, a serious disease affecting more than
      200 million people in the tropics. The fucosylated structures are thought to play
      an important role in the immunology of schistosomiasis. Defined schistosomal
      oligosaccharides that enable immunological studies are difficult to obtain from
      natural sources. Therefore, we have chemically synthesized spacer-linked GlcNAc,
      Fucalpha1-3GlcNAc, Fucalpha1-2Fucalpha1-3GlcNAc, and Fucalpha1-2Fucalpha1
      2Fucalpha1-3GlcNAc. This series of linear oligosaccharides was used to screen a
      library of anti-schistosome monoclonal antibodies by surface plasmon resonance
      spectroscopy. Interestingly, the reactive antibodies could be grouped according
      to their specificity for the different oligosaccharides tested, showing that
      these oligosaccharides form different immunological entities based on the number
      and linkage of the fucose residues. Subsequently, the thus defined monoclonal
      antibodies were used to visualize the expression of the corresponding
      oligosaccharide epitopes by adult Schistosoma mansoni worms.

PMID- 15848769
TI  - Cytotoxicities, cell cycle and caspase evaluations of 1,6-diaryl-3(Z)-hexen-1,5
      diynes, 2-(6-aryl-3(Z)-hexen-1,5-diynyl)anilines and their derivatives.
AB  - Compounds 3, 6-7, 9-10, 15-17, and 20-21 showed growth inhibition effects on a
      full panel of 60 human cancer cell lines, and most of the average IC50 values of
      the indicated analogues were from < 0.01 to 96.6 microM, in which analogues 16
      and 17 revealed the highest cytotoxic activity with the cancer cell lines at 10(
      7) M concentration range. During the cell cycle analysis, a moderate to high
      apoptotic progress induction was shown by 3, 9, 16-17, and 20 compared with the
      control, which 2-(6-(2-thienyl)-3(Z)-hexen-1,5-diynyl)aniline 16 showed the
      highest apoptotic effect. Structures 16-17 displayed a significant G2/M phase
      arrest in the cell growth cycle compared with other derivatives, which the
      proportions of the G2/M phase cells were accumulated to 71.5% and 82.6%,
      respectively. Moreover, the colorimetric assay of 16-17 also provided advanced
      evidence to the relationship between the compounds and the caspase-3 enzyme,
      which was one of the major promoters of apoptotic effect.

PMID- 15848770
TI  - Design, synthesis, and biological evaluation of 10-methanesulfonyl-DDACTHF, 10
      methanesulfonyl-5-DACTHF, and 10-methylthio-DDACTHF as potent inhibitors of GAR
      Tfase and the de novo purine biosynthetic pathway.
AB  - The synthesis and evaluation of 10-methanesulfonyl-DDACTHF (1), 10
      methanesulfonyl-5-DACTHF (2), and 10-methylthio-DDACTHF (3) as potential
      inhibitors of glycinamide ribonucleotide transformylase (GAR Tfase) and
      aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase) are
      reported. The compounds 10-methanesulfonyl-DDACTHF (1, K(i) = 0.23 microM), 10
      methanesulfonyl-5-DACTHF (2, K(i) = 0.58 microM), and 10-methylthio-DDACTHF (3,
      K(i) = 0.25 microM) were found to be selective and potent inhibitors of
      recombinant human GAR Tfase. Of these, 3 exhibited exceptionally potent, purine
      sensitive growth inhibition activity (3, IC50 = 100 nM) against the CCRF-CEM cell
      line being 3-fold more potent than Lometrexol and 30-fold more potent than the
      parent, unsubstituted DDACTHF, whereas 1 and 2 exhibited more modest growth
      inhibition activity (1, IC50 = 1.0 microM and 2, IC50 = 2.0 microM).

PMID- 15848771
TI  - Synthesis and biological evaluation of alpha- and gamma-carboxamide derivatives
      of 10-CF3CO-DDACTHF.
AB  - Structurally-related, but non-polyglutamylatable, derivatives of 10-CF3CO-DDACTHF
      (1), which incorporate L-glutamine (2) and L-isoglutamine (3) in place of L
      glutamate, were prepared and evaluated as inhibitors of recombinant human (rh)
      GAR Tfase. While the L-glutamate alpha-carboxamide derivative 3 was much less
      effective as a rhGAR Tfase inhibitor (K(i) = 4.8 microM) and inactive in cellular
      functional assays, the gamma-carboxamide derivative 2 was found to be a potent
      and selective rhGAR Tfase inhibitor (K(i) = 0.056 microM) being only 4-fold less
      potent than 1 (K(i) = 0.015 microM). Moreover, 2 was effective in cellular
      functional assays exhibiting purine sensitive cytotoxic activity (IC50 = 300 nM,
      CCRF-CEM) only 20-fold less potent than 1 (IC50 = 16 nM), consistent with
      inhibition of de novo purine biosynthesis via selective inhibition of GAR Tfase.
      Like 1, 2 is transported into the cell by the reduced folate carrier. Unlike 1,
      the functional activity of 2 is not dependent upon FPGS polyglutamylation.

PMID- 15848772
TI  - Synthesis and biological evaluation of N-[4-[5-(2,4-diamino-6-oxo-1,6
      dihydropyrimidin-5-yl)-2-(2,2,2-trifluoroacetyl)pentyl]benzoyl]-L-glutamic acid
      as a potential inhibitor of GAR Tfase and the de novo purine biosynthetic
      pathway.
AB  - The synthesis and evaluation of N-[4-[5-(2,4-diamino-6-oxo-1,6-dihydropyrimidin-5
      yl)-2-(2,2,2-trifluoroacetyl)pentyl]benzoyl]-L-glutamic acid (2) as an inhibitor
      of glycinamide ribonucleotide transformylase (GAR Tfase) and aminoimidazole
      carboxamide ribonucleotide transformylase (AICAR Tfase) are reported. The
      inhibitor 2 was prepared in a convergent synthesis involving C-alkylation of
      methyl 4-(4,4,4-trifluoro-3-dimethylhydrazonobutyl)benzoate with 1-chloro-3
      iodopropane followed by construction of the pyrimidinone ring. Compound 2 was
      found to be an effective inhibitor of recombinant human GAR Tfase (K(i) = 0.50
      microM), whereas it was inactive (K(i) > 100 microM) against E. coli GAR Tfase as
      well as recombinant human AICAR Tfase. Compound 2 exhibited modest, purine
      sensitive growth inhibitory activity against the CCRF-CEM cell line (IC50 = 6.0
      microM).

PMID- 15848773
TI  - The creation of a new monster: MRSA and MRSI--important emerging veterinary and
      zoonotic diseases.

PMID- 15848774
TI  - The multifactorial nature of cattle lameness: a few more pieces of the jigsaw.

PMID- 15848775
TI  - Further insights into the susceptibility of broilers to ascites.

PMID- 15848776
TI  - A review of porcine circovirus 2-associated syndromes and diseases.
AB  - Clinical expression of porcine circovirus 2 (PCV2) infection in swine may result
      in several distinct syndromes and diseases including post-weaning multisystemic
      wasting syndrome (PMWS), porcine dermatitis and nephropathy syndrome (PDNS),
      reproductive failure, porcine respiratory disease complex, granulomatous
      enteritis, necrotizing lymphadenitis, and possibly exudative epidermitis.
      Association of PCV2 with congenital tremor in piglets is still controversial. The
      extent of the involvement of PCV2 in swine disease other than PMWS is currently
      poorly understood. This review concentrates on PCV-2-associated syndromes and
      diseases other than PMWS.

PMID- 15848777
TI  - Dehorning and disbudding distress and its alleviation in calves.
AB  - Dehorning and disbudding are routine painful procedures carried out on cattle to
      facilitate management. The pain caused by these procedures and its alleviation
      may be evaluated by monitoring behaviour and physiological responses, and by
      measuring their effects on weight gain. The cortisol response to cautery
      disbudding is significantly smaller than that to amputation dehorning which
      infers that the latter is more painful. Amputation dehorning stimulates a defined
      cortisol response with a rapid rise to a peak value within 30 min followed by a
      decline to a plateau which then declines to pre-treatment values after about 8 h.
      A cornual nerve blockade using lignocaine virtually eliminates the escape
      behaviour seen during disbudding and dehorning and reduces the plasma cortisol
      response to dehorning for about 2 h. Thereafter there is an increase in the
      plasma cortisol concentration, a delayed response, which lasts for about 6 h. A
      cornual nerve blockade, using lignocaine combined with cauterizing the wound
      caused by amputation dehorning, virtually eliminates the cortisol response as
      does combining a lignocaine blockade with the non-steroidal anti-inflammatory
      drug (NSAID) ketoprofen. When xylazine is combined with a cornual nerve blockade
      using lignocaine before dehorning, the cortisol response is virtually eliminated
      for about 3 h. When this regime is used before cautery disbudding and includes a
      NSAID given before and after disbudding the behaviour of calves so treated
      suggests that pain may be alleviated for 24 h. Cautery disbudding is preferable
      to amputation dehorning, but for optimal pain relief xylazine sedation, local
      anaesthesia and a NSAID should be used with both procedures.

PMID- 15848778
TI  - Production and growth related disorders and other metabolic diseases of poultry-
      a review.
AB  - In humans, metabolic complaints may be associated with a failure in one of the
      body hormone or enzyme systems, a storage disease related to lack of metabolism
      of secretory products because of the lack of production of a specific enzyme, or
      the breakdown or reduced activity of some metabolic function. Some of these
      disorders also occur in poultry, as do other important conditions such as those
      associated with increased metabolism, rapid growth or high egg production that
      result in the failure of a body system because of the increased work-load on an
      organ or system. These make up the largest group of poultry diseases classified
      as metabolic disorders and cause more economic loss than infectious agents.
      Poultry metabolic diseases occur primarily in two body systems: (1)
      cardiovascular ailments, which in broiler chickens and turkeys are responsible
      for a major portion of the flock mortality; (2) musculoskeletal disorders, which
      account for less mortality, but in broilers and turkeys slow down growth (thereby
      reducing profit), and cause lameness, which remains a major welfare concern. In
      addition, conditions such as osteoporosis and hypocalcaemia in table-egg chickens
      reduce egg production and can kill.

PMID- 15848779
TI  - New surgical approach to the plantar fetlock joint through the digital flexor
      tendon sheath wall and suspensory ligament apparatus in cases of concurrent
      septic synovitis in two cattle.
AB  - A new surgical approach to the infected fetlock joint is described in two cattle
      suffering from septic tenosynovitis of the lateral digital flexor tendon sheaths
      of the right lateral hind-digits with concurrent septic serofibrinous arthritis
      of the adjoining fetlock joints, caused by penetrating wounds. In both patients,
      the infected sheaths were opened and the superficial and deep digital flexor
      tendons were removed. Intraoperatively, a small entry through the fetlock joint
      capsule was detected, directly distal to the lateral proximal sesamoid bone. The
      tract was surgically enlarged and a second approach into the plantar fetlock
      joint pouch was created proximally by making a 3 cm long and 0.5 cm wide incision
      between the two lateral suspensory ligament branches. This allowed easy access to
      the plantar joint pouch, removal of fibrin clots and an effective joint lavage
      using 5L of sterile saline solution. The incisions of the fetlock joint capsules
      remained unsutured and were drained using soft polyurethane foam to preclude
      premature closure. The tendon sheath wounds remained unsutured. In both patients,
      the digital flexor tendon sheath and the fetlock joint were lavaged daily for the
      following three days. The infection was eliminated in both cattle and both fully
      recovered without residual lameness.

PMID- 15848780
TI  - Effects of feeding intensity during the dry period on leukocyte and lymphocyte
      sub-populations, neutrophil function and health in periparturient dairy cows.
AB  - The objective of this investigation was to study (1) the numbers of leukocytes,
      (2) the proportions of lymphocytes expressing CD4, CD8, WC1, B or IL2R and (3)
      neutrophil phagocytosis and oxidative burst activity in blood around parturition
      in three groups of dairy cows fed different levels of a total mixed ration during
      the last eight weeks before calving. All cows were fed ad libitum during the
      first eight weeks of lactation. Serum concentration of the acute phase protein
      serum amyloid A (SAA), the milk somatic cell count (SCC) and disease incidence
      were also recorded. Special emphasis was given to the weeks just before and just
      after calving as dairy cows are known to be immune suppressed during this period.
      Dry period diet had only minor effects on leukocyte numbers, and did not
      influence neutrophil phagocytosis and oxidative burst. In addition, no effect was
      observed on disease incidence or SAA concentrations. However, an increase in the
      proportion of B-lymphocytes and a decrease in the proportion of WC1+ T
      lymphocytes were observed after calving in cows fed high or low energy rations
      during the dry period, but not in cows fed a medium energy ration. The weeks just
      before and after parturition were characterised by neutrophilia, eosinopenia,
      lymphopenia and monocytosis, but time had no effect on neutrophil phagocytosis
      and oxidative burst. The proportions of CD4+, CD8+, B+ and IL-2R+ lymphocytes
      increased in early lactation relative to the mid dry period. In addition, the
      concentration of SAA increased dramatically at calving. The results emphasise the
      need for more studies to clarify the complex interactions between nutrition and
      immunity during the peripartum period in dairy cattle.

PMID- 15848781
TI  - Collection of exhaled breath condensate and analysis of hydrogen peroxide as a
      potential marker of lower airway inflammation in cats.
AB  - The objective of this study was to describe a standardised and non-invasive
      method for exhaled breath condensate (EBC) collection in cats and to test whether
      determination of hydrogen peroxide (H(2)O(2)) in EBC might be used as marker of
      lower airway inflammation. The technique of barometric whole body plethysmography
      for cats was combined with a system to condense the effluent air from the
      plethysmograph, allowing simultaneous EBC collection and respiratory pattern
      measurement. H(2)O(2) was determined spectrophotometrically. Eighteen
      experimental cats were used to investigate the impact on EBC volume and EBC
      H(2)O(2) of plethysmograph ventilation rate, collection duration, sample
      stability, within-day and day-to-day variability. After determination of a
      standardised EBC collection procedure, correlation analyses between EBC H(2)O(2)
      and bronchoalveolar lavage (BAL) cytology of healthy and allergen-challenged
      Ascaris suum (AS)-sensitised cats were performed. A significant and positive
      correlation between EBC H(2)O(2) and bronchoalveolar lavage (BAL) neutrophil% was
      found in healthy cats (P < 0.001, r = 0.55), whereas in AS-sensitised cats,
      correlation with BAL eosinophil% was significant (P < 0.005, r = 0.61). H(2)O(2)
      was increased after an allergen challenge in AS-sensitised cats (n = 6, 0.56+/
      0.12 versus 1.08+/-0.35 micromol/L, P < 0.05). This study proposes a non
      invasive, well tolerated and repeatable method of EBC collection for cats and
      suggests that EBC H(2)O(2) might be used as non-invasive biomarker for monitoring
      lower airway inflammation.

PMID- 15848782
TI  - Age-related changes in metabolic properties of equine skeletal muscle associated
      with muscle plasticity.
AB  - The purpose of the present study was to determine the age-related changes in
      myosin heavy chain (MHC) composition and muscle oxidative and glycolytic capacity
      in 18 horses ranging in age from two to 30 years. Muscle samples were collected
      by excisional biopsy of the semimebranosus muscle. MHC expression and the key
      enzymatic activities were measured. There was no significant correlation between
      horse age and the proportions of type-IIA and type-IIX MHC isoforms. The
      percentage of type-I MHC isoforms decreased with advancing age. Muscle citrate
      synthase activity decreased, whereas lactate dehydrogenase activity increased
      with increasing age. Muscle 3-OH acyl CoA dehydrogenase activity did not change
      with ageing. The results suggest that, similar to humans, the oxidative capacity
      of equine skeletal muscle decreases with age. The age-related changes in muscle
      metabolic properties appear to be consistent with an age-related transition in
      MHC isoforms of equine skeletal muscle that shifts toward more glycolytic
      isoforms with age.

PMID- 15848783
TI  - Characteristics of live bovine herpesvirus-1 vaccines.
AB  - The common disease caused by bovine herpes virus 1 infection is febrile
      rhinotracheitis (FRT) and under certain conditions the virus is strongly
      implicated in pre-disposing cattle to pneumonic pasteurellosis. These illnesses
      account for a significant economic loss in the cattle industry worldwide and
      vaccination is widely applied. In naive cattle, and for a short period of time,
      old and new vaccines significantly reduce clinical signs of FRT and also virus
      shedding. A single intranasal vaccination affords significant protection in face
      of maternally derived antibodies, and the protection can be significantly
      prolonged by a booster intramuscular vaccination. Current data recommend
      vaccination in face of an outbreak and vaccines appear safe for pregnant cattle.

PMID- 15848784
TI  - Synergistic action of E. coli endotoxin and Pasteurella multocida type A for the
      induction of bronchopneumonia in pigs.
AB  - This study aimed to investigate whether Escherichia coli endotoxin (LPS) may
      predispose the lung to an infection with Pasteurella multocida type A (Pma) and
      to determine the LPS concentration needed to reproduce clinical signs of
      bronchopneumonia. Twenty-four hours before inoculating Pma or sterile growth
      medium, piglets were tracheally instilled with 10, 100 or 400 microg/kg LPS.
      Cough, body temperature, daily weight gain (DWG) bronchoalveolar lavage fluid
      (BALF) cells and volume of pneumonic lung were measured. Changes in breathing
      pattern (Penh) were assessed by whole body barometric plethysmography. No
      significant changes were observed in Pma-treated or in control animals. Each LPS
      doses induced DWG reduction while the higher generated a severe subacute
      interstitial pneumonia causing hyperthermia and an increase in Penh. The
      combination of the lower LPS doses with Pma produced an asymptomatic
      bronchopneumonia leading to DWG reduction, rise in Penh and an increase in BALF
      macrophages and neutrophils. With 400 microg/kg LPS, Pma worsened the
      inflammatory process as illustrated by cough, hyperthermia, major DWG reduction
      and by a greater Penh response. Lung lesions consisted of severe exudative
      bronchopneumonia. We concluded that LPS may negatively influence growth,
      predispose to persisting lung inflammatory process and promote Pma infection
      depending on the dose previously administered.

PMID- 15848785
TI  - Effects of type of forage fed to dairy heifers: associations between claw
      characteristics, clinical lameness, environment and behaviour.
AB  - Heifers were reared separately on wet fermented (WF) (grass silage based) or dry
      unfermented (DU) (straw based) diets. Clinical lameness was recorded and physical
      claw attributes were measured regularly, up to six months after calving at
      approximately two years of age. Two months before calving, some aspects of animal
      behaviour and the properties of slurry were studied. The incidence of lameness
      due to claw horn lesions was significantly higher (P < 0.01) in WF than in DU. WF
      suffered more serious heel erosion prior to calving (P < 0.05) and had softer
      claw horn at two (heel and axial sole) out of five sites throughout (P < 0.01 and
      P < 0.05). The slurry produced by WF had lower total solids content (P < 0.05)
      and viscosity (P < 0.001). WF spent longer standing and feeding (P < 0.001). It
      is proposed that standing for longer in less viscous slurry contributed to softer
      claw horn and more severe heel erosion, predisposing WF to claw horn lesions
      causing lameness. Reducing contact with low dry matter slurry is recommended for
      improving claw health.

PMID- 15848786
TI  - Pharmacokinetics of an ampicillin-sulbactam combination after intravenous and
      intramuscular administration to neonatal calves.
AB  - The pharmacokinetics of a 2:1 ampicillin-sulbactam combination after intravenous
      (i.v.) and intramuscular (i.m.) injection at a single dose rate of 20 mg/kg
      bodyweight (13.33 mg/kg of sodium ampicillin and 6.67 mg/kg of sodium sulbactam)
      were studied in 10-day-old neonatal calves (n = 10). The plasma concentration
      time data of both antibiotics were best fitted to an open two-compartment model
      after i.v. administration. After i.m. administration, an open two-compartment
      model demonstrated first order absorption. The apparent volumes of distribution
      of ampicillin and sulbactam, calculated by the area method, were 0.20+/-0.01 and
      0.18+/-0.01 L/kg, respectively, and the total body clearances were 0.51+/-0.03
      and 0.21+/-0.01 L/kg h. The elimination half-lives of ampicillin after i.v. and
      i.m. administration were 0.99+/-0.03 and 1.01+/-0.02 h, respectively, whereas for
      sulbactam the half-lives were 2.24+/-0.02 and 3.44+/-0.94 h. The bioavailability
      after i.m. injection was high and similar for both drugs (70.31+/-0.2% for
      ampicillin and 68.62+/-4.44% for sulbactam). The mean peak plasma concentrations
      of ampicillin and sulbactam were reached at similar times (0.47+/-0.02 and 0.72+/
      0.01 h, respectively) and peak concentrations were also similar but not
      proportional to the dose administered (17.88+/-0.91 mg/L of ampicillin and
      12.92+/-0.79 mg/L of sulbactam). Both drugs had similar pharmacokinetic behaviour
      after i.m. administration. Since the plasma concentrations of sulbactam were
      consistently higher during the elimination phase of their disposition,
      consideration could be given to formulating the ampicillin-sulbactam combination
      in a ratio higher than 2:1.

PMID- 15848787
TI  - Studies on rickets and osteomalacia in Bactrian camels (Camelus bactrianus).
AB  - Epidemiological studies have indicated incidences of 32.9% and 27.8% for rickets
      and osteomalacia, respectively, in Bactrian camels (Camelus bactrianus), but
      there is an increased incidence under drought conditions, sometimes reaching 75%.
      We have found that concentrations of phosphorus and copper in forage and soil
      samples in a drought affected area were significantly lower than in a control
      area or normal reference values (P < 0.01) ; the mean Ca:P ratio in the forages
      was 50:1. The phosphorus content of blood and hair from affected camels was
      significantly less than that in controls (P < 0.01) and concentrations of copper
      in the liver and kidney were significantly lower in affected camels than control
      animals (P < 0.01); the concentrations of triiodothyronine (T(3)), thyroxine
      (T(4)) and parathyroid hormone (PTH) in the serum from affected animals were
      significantly higher than those from healthy controls (P < 0.01); serum inorganic
      phosphorus and ceruloplasmin levels were lower than those in the controls (P <
      0.01 or P < 0.05); the concentrations of serum alpha-globulin and beta-globulin
      were significantly higher in the affected camels than in the healthy controls (P
      < 0.01). The pathological changes seen in camels affected with rickets included
      porous, brittle, light, osteoporotic bones that were susceptible to fractures and
      had less resistance to cutting and sawing. Wrist joints were enlarged with an
      apparent bowing of the long bones in forelimb and with typical broadening of the
      epiphyses. In adult female camels, many enlarged scars were often seen in ribs
      indicating earlier fractures. The disease could be cured with supplementary bone
      meal, phosphate or mineral mixtures and in field investigations clinical signs
      disappeared within 15 days. Over the same period, the concentrations of
      phosphorus and alkaline phosphatase in blood returned to normal. The disease may
      be effectively prevented by use of mineral blocks (block salt licks) or dosing
      orally with copper, selenium and cobalt soluble glass boluses. We conclude that
      rickets and osteomalacia are mainly caused by phosphorus and copper deficiencies
      in the pasture.

PMID- 15848788
TI  - Identification of viral pathogens in aborted fetuses and stillborn piglets from
      cases of swine reproductive failure in Spain.
AB  - The objective of the present study was to determine the presence of recognised
      abortifacient viruses such as porcine reproductive and respiratory virus (PRRSV),
      Aujeszky's disease virus (ADV), porcine parvovirus (PPV) and porcine circovirus
      type 2 (PCV2), in tissues from aborted fetuses and stillborn neonates in cases of
      late reproductive failure in swine. A total of 293 specimens (fetuses aborted in
      the last third of gestation and stillborn piglets) from 100 different cases of
      late-term abortions and premature farrowing from 15 different Spanish provinces
      were studied. PRRSV was detected in 9/100 cases by RT-PCR. Only 1/100 cases
      analysed (corresponding to a late-term aborted fetus with a negative PRRSV RT-PCR
      result) was positive for PCV2 by PCR. Neither ADV (monitored by viral isolation
      plus antigen detection) nor PPV (monitored by ELISA antigen capture test)
      infection was identified. The results suggest that PRRSV is one of the most
      important infectious agents, if not the most relevant one, associated with fetal
      infection leading to abortion or premature farrowing in Spain. Moreover, other
      viral pathogens such as ADV, PPV and PCV2 seem to have a minor impact on
      reproductive disease.

PMID- 15848789
TI  - Fungal isolation and identification in 21 cases of guttural pouch mycosis in
      horses (1998-2002).
AB  - This aetiological study of guttural pouch mycosis (GPM) in the horse was based on
      the retrospective study of 21 horses brought into the National Veterinary School
      of Lyon (France) between 1998 and 2002. Biopsies were taken from the lesions
      caused by GPM during endoscopic examination. In 87% of the cases, direct
      examination gave positive results, whereas 43% of the cultures were found to be
      negative. The main fungi observed were Aspergillus fumigatus (in three cases), A.
      versicolor (in two cases, together with other fungi), and A. nidulans and A.
      niger (one case each). In six cases, the Aspergillus species could not be
      identified. In two cases, cleistothecia and/or Hulle cells were observed. In
      three cases, fungi other than Aspergillus were seen, mixed or not with
      Aspergillus. These results underline the importance of Aspergillus fumigatus in
      the development of GPM in horses.

PMID- 15848790
TI  - Leptospiral antibodies in captive lion tamarins (Leontopithecus sp) in Brazil.
AB  - Serum samples from 73 lion tamarins of three species living at the Centro de
      Primatologia do Rio de Janeiro were tested for antibodies against serovars of
      Leptospira interrogans by microscopic agglutination test. Antibodies were
      detected in serum samples of 15% of tested samples. Seroreactivity prevalence was
      lower than that described in other non-human primates and could be explained by
      the arboreal behaviour of these animals. Icterohaemorrhagiae was the most common
      serogroup.

PMID- 15848791
TI  - Altered platelet aggregation and coagulation disorders related to clinical
      findings in 30 dogs naturally infected by Leishmania infantum.

PMID- 15848792
TI  - Variation in immunogenicity of ruminant pestiviruses as determined by the
      neutralisation assay.
AB  - Immunogenicity in naive three-month-old Friesian bull calves of nine ruminant
      pestiviruses, three each of type 1 bovine virus diarrhoea virus (BVDV), type 2
      BVDV and border disease virus (BDV) was directly compared in reciprocal cross
      neutralisation tests using sera obtained eight weeks after intranasal and
      intravenous inoculation with live virus. Cytopathic (CP) type 1 BVDV strain C86,
      non-cytopathic (NCP) type 2 BVDV strain 890 and NCP BDV strain V2536/2 were found
      to elicit significantly broad cross-neutralising antibodies against viruses in
      other species whereas other virus strains in all three species produced a much
      more pronounced homologous and/or species specific response. Results are clearly
      relevant in the selection of strains for vaccines against diseases caused by
      these successful, economically important ubiquitous viruses.

PMID- 15848793
TI  - New exchanges in eph-dependent growth cone dynamics.
AB  - The Eph receptor tyrosine kinases and their ephrin ligands play a pivotal role
      during axon pathfinding and neural circuitry formation. A prominent way in which
      Eph receptors sculpt cellular morphology is by remodeling the actin cytoskeleton
      and the surrounding plasma membrane through the regulation of Rho family GTPases.
      Two articles in this issue of Neuron (Sahin et al. and Cowan et al.) shed light
      on how Eph receptors recruit guanine nucleotide exchange factors for Rho family
      GTPases to modulate growth cone dynamics.

PMID- 15848794
TI  - Surprising twists to exocyst function.
AB  - What do neurons use the exocyst complex for? In this issue of Neuron, using
      mutations in one exocyst component, Mehta et al. reach the surprising conclusion
      that exocyst function is divisible: different components play distinct roles.
      These studies also suggest that the exocyst may regulate membrane insertion of
      cell adhesion molecules required for synaptic partner choice.

PMID- 15848795
TI  - Perception without a thalamus how does olfaction do it?
AB  - The olfactory system has generated considerable interest in recent years, mainly
      focused on receptor genes and early olfactory processing. In this issue of
      Neuron, Mori et al. focus centrally, providing evidence for slow- and fast-wave
      states in olfactory cortex that appear to gate the inflow of information
      underlying conscious smell perception.

PMID- 15848796
TI  - Sugar codes for axons?
AB  - Proteoglycans are complex macromolecules with the potential for extraordinary
      diversity. Several recent studies have demonstrated important roles for heparan
      sulfate and chondroitin sulfate proteoglycans (HSPGs and CSPGs) in axon
      pathfinding and have linked HSPGs to specific signaling pathways. More
      speculatively, there are hints of a "sugar code," in which specific sugar
      modifications might act instructively in guidance decisions. This raises the
      intriguing possibility that the complexity of neuronal wiring may in part reflect
      the complexity of proteoglycan modifications.

PMID- 15848797
TI  - The basal forebrain cholinergic system is essential for cortical plasticity and
      functional recovery following brain injury.
AB  - A reorganization of cortical representations is postulated as the basis for
      functional recovery following many types of nervous system injury. Neuronal
      mechanisms underlying this form of cortical plasticity are poorly understood. The
      present study investigated the hypothesis that the basal forebrain cholinergic
      system plays an essential role in enabling the cortical reorganization required
      for functional recovery following brain injury. The results demonstrate that
      functional recovery following cortical injury requires basal forebrain
      cholinergic mechanisms and suggest that the basis for this recovery is the
      cholinergic-dependent reorganization of motor representations. These findings
      raise the intriguing possibility that deficits in cholinergic function may limit
      functional outcomes following nervous system injury.

PMID- 15848798
TI  - Development of long-term dendritic spine stability in diverse regions of cerebral
      cortex.
AB  - Synapse formation and elimination occur throughout life, but the magnitude of
      such changes at distinct developmental stages remains unclear. Using transgenic
      mice overexpressing yellow fluorescent protein and transcranial two-photon
      microscopy, we repeatedly imaged dendritic spines on the apical dendrites of
      layer 5 pyramidal neurons. In young adolescent mice (1-month-old), 13%-20% of
      spines were eliminated and 5%-8% formed over 2 weeks in barrel, motor, and
      frontal cortices, indicating a cortical-wide spine loss during this developmental
      period. As animals mature, there is also a substantial loss of dendritic
      filopodia involved in spinogenesis. In adult mice (4-6 months old), 3%-5% of
      spines were eliminated and formed over 2 weeks in various cortical regions. Over
      18 months, only 26% of spines were eliminated and 19% formed in adult barrel
      cortex. Thus, after a concurrent loss of spines and spine precursors in diverse
      regions of young adolescent cortex, spines become stable and a majority of them
      can last throughout life.

PMID- 15848799
TI  - Eph-dependent tyrosine phosphorylation of ephexin1 modulates growth cone
      collapse.
AB  - Ephs regulate growth cone repulsion, a process controlled by the actin
      cytoskeleton. The guanine nucleotide exchange factor (GEF) ephexin1 interacts
      with EphA4 and has been suggested to mediate the effect of EphA on the activity
      of Rho GTPases, key regulators of the cytoskeleton and axon guidance. Using
      cultured ephexin1-/- mouse neurons and RNA interference in the chick, we report
      that ephexin1 is required for normal axon outgrowth and ephrin-dependent axon
      repulsion. Ephexin1 becomes tyrosine phosphorylated in response to EphA signaling
      in neurons, and this phosphorylation event is required for growth cone collapse.
      Tyrosine phosphorylation of ephexin1 enhances ephexin1's GEF activity toward RhoA
      while not altering its activity toward Rac1 or Cdc42, thus changing the balance
      of GTPase activities. These findings reveal that ephexin1 plays a role in axon
      guidance and is regulated by a switch mechanism that is specifically tailored to
      control Eph-mediated growth cone collapse.

PMID- 15848800
TI  - Vav family GEFs link activated Ephs to endocytosis and axon guidance.
AB  - Ephrin signaling through Eph receptor tyrosine kinases can promote attraction or
      repulsion of axonal growth cones during development. However, the mechanisms that
      determine whether Eph signaling promotes attraction or repulsion are not known.
      We show here that the Rho family GEF Vav2 plays a key role in this process. We
      find that, during axon guidance, ephrin binding to Ephs triggers Vav-dependent
      endocytosis of the ligand-receptor complex, thus converting an initially adhesive
      interaction into a repulsive event. In the absence of Vav proteins, ephrin-Eph
      endocytosis is blocked, leading to defects in growth cone collapse in vitro and
      significant defects in the ipsilateral retinogeniculate projections in vivo.
      These findings suggest an important role for Vav family GEFs as regulators of
      ligand-receptor endocytosis and determinants of repulsive signaling during axon
      guidance.

PMID- 15848801
TI  - Mutations in Drosophila sec15 reveal a function in neuronal targeting for a
      subset of exocyst components.
AB  - The exocyst is a complex of proteins originally identified in yeast that has been
      implicated in polarized secretion. Components of the exocyst have been implicated
      in neurite outgrowth, cell polarity, and cell viability. We have isolated an
      exocyst component, sec15, in a screen for genes required for synaptic
      specificity. Loss of sec15 causes a targeting defect of photoreceptors that
      coincides with mislocalization of specific cell adhesion and signaling molecules.
      Additionally, sec15 mutant neurons fail to localize other exocyst members like
      Sec5 and Sec8, but not Sec6, to neuronal terminals. However, loss of sec15 does
      not cause cell lethality in contrast to loss of sec5 or sec6. Our data suggest a
      role of Sec15 in an exocyst-like subcomplex for the targeting and subcellular
      distribution of specific proteins. The data also show that functions of other
      exocyst components persist in the absence of sec15, suggesting that different
      exocyst components have separable functions.

PMID- 15848802
TI  - Impaired synapse function during postnatal development in the absence of CALEB,
      an EGF-like protein processed by neuronal activity.
AB  - In an attempt to characterize the molecular components by which electric activity
      influences the development of synapses, we searched for cell surface proteins
      modulated by calcium influx and glutamate receptor activity. Here, we report that
      neuronal depolarization facilitates the conversion of CALEB, which results in a
      truncated transmembrane form with an exposed EGF domain. To characterize the role
      of CALEB in synapse development, synaptic features were investigated in slices of
      the colliculus superior from CALEB-deficient mice. In the absence of CALEB, the
      number of synapses and their morphological characteristics remained unchanged.
      However, in CALEB-deficient mice, synapses displayed higher paired-pulse ratios,
      less depression during prolonged repetitive activation, a lower rate of
      spontaneous postsynaptic currents, and a lower release probability at early but
      not mature postnatal stages. Our findings indicate that CALEB provides a
      molecular basis for maintaining normal release probability at early developmental
      stages.

PMID- 15848803
TI  - Tyramine Functions independently of octopamine in the Caenorhabditis elegans
      nervous system.
AB  - Octopamine biosynthesis requires tyrosine decarboxylase to convert tyrosine into
      tyramine and tyramine beta-hydroxylase to convert tyramine into octopamine. We
      identified and characterized a Caenorhabditis elegans tyrosine decarboxylase
      gene, tdc-1, and a tyramine beta-hydroxylase gene, tbh-1. The TBH-1 protein is
      expressed in a subset of TDC-1-expressing cells, indicating that C. elegans has
      tyraminergic cells that are distinct from its octopaminergic cells. tdc-1 mutants
      have behavioral defects not shared by tbh-1 mutants. We show that tyramine plays
      a specific role in the inhibition of egg laying, the modulation of reversal
      behavior, and the suppression of head oscillations in response to anterior touch.
      We propose a model for the neural circuit that coordinates locomotion and head
      oscillations in response to anterior touch. Our findings establish tyramine as a
      neurotransmitter in C. elegans, and we suggest that tyramine is a genuine
      neurotransmitter in other invertebrates and possibly in vertebrates as well.

PMID- 15848804
TI  - Modulation of triheteromeric NMDA receptors by N-terminal domain ligands.
AB  - NMDA receptors (NMDARs) are heteromeric assemblies of NR1 and NR2(A-D) subunits
      with properties heavily influenced by the type of NR2 subunit incorporated. While
      NMDARs with only one type of NR2 subunit have been extensively characterized,
      little is known about receptors containing two different NR2 subunits, despite
      compelling evidence that such triheteromeric receptors exist in vivo. We used a
      point-mutation approach that allows isolation of recombinant triheteromeric
      NMDARs possessing two different NR2 N-terminal domains (NTDs). We show that in
      receptors associating the NR2A-NTD (sensing nanomolar Zn) and the NR2B-NTD
      (sensing ifenprodil), each NTD binding site retains selective high affinity for
      its ligand. However, each ligand produces only partial inhibition, and maximal
      inhibition requires occupancy of both NR2-NTDs by their respective ligands.
      Similarly, NR1/2A/2C receptors are inhibited by zinc with high potency but low
      efficacy. Therefore, interactions between homologous N-terminal domains determine
      the unique pharmacological properties of triheteromeric NMDARs.

PMID- 15848805
TI  - Adenosine mediation of presynaptic feedback inhibition of glutamate release.
AB  - Conditions of increased metabolic demand relative to metabolite availability are
      associated with increased extracellular adenosine in CNS tissue. Synaptic
      activation of postsynaptic NMDA receptors on neurons of the cholinergic brainstem
      arousal center can increase sufficient extracellular adenosine to act on
      presynaptic A1 adenosine receptors (A1ADRs) of glutamate terminals, reducing
      release from the readily releasable pool. The time course of the adenosine
      response to an increase in glutamate release is slow (tau > 10 min), consistent
      with the role of adenosine as a fatigue factor that inhibits the activity of
      cholinergic arousal centers to reduce arousal.

PMID- 15848806
TI  - State-dependent sensory gating in olfactory cortex.
AB  - Sensory systems show behavioral state-dependent gating of information flow that
      largely depends on the thalamus. Here we examined whether the state-dependent
      gating occurs in the central olfactory pathway that lacks a thalamic relay. In
      urethane-anesthetized rats, neocortical EEG showed a periodical alternation
      between two states: a slow-wave state (SWS) characterized by large and slow waves
      and a fast-wave state (FWS) characterized by faster waves. Single-unit recordings
      from olfactory cortex neurons showed robust spike responses to adequate odorants
      during FWS, whereas they showed only weak responses during SWS. The state
      dependent change in odorant-evoked responses was observed in a majority of
      olfactory cortex neurons, but in only a small percentage of olfactory bulb
      neurons. These findings demonstrate a powerful state-dependent gating of odor
      information in the olfactory cortex that works in synchrony with the gating of
      other sensory systems. They suggest a state-dependent switchover of signal
      processing modes in the olfactory cortex.

PMID- 15848807
TI  - Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in
      mice.
AB  - The finding of orexin/hypocretin deficiency in narcolepsy patients suggests that
      this hypothalamic neuropeptide plays a crucial role in regulating
      sleep/wakefulness states. However, very little is known about the synaptic input
      of orexin/hypocretin-producing neurons (orexin neurons). We applied a transgenic
      method to map upstream neuronal populations that have synaptic connections to
      orexin neurons and revealed that orexin neurons receive input from several brain
      areas. These include the amygdala, basal forebrain cholinergic neurons, GABAergic
      neurons in the preoptic area, and serotonergic neurons in the median/paramedian
      raphe nuclei. Monoamine-containing groups that are innervated by orexin neurons
      do not receive reciprocal connections, while cholinergic neurons in the basal
      forebrain have reciprocal connections, which might be important for consolidating
      wakefulness. Electrophysiological study showed that carbachol excites almost one
      third of orexin neurons and inhibits a small population of orexin neurons. These
      neuroanatomical findings provide important insights into the neural pathways that
      regulate sleep/wakefulness states.

PMID- 15848808
TI  - Distinct neural signatures for safety and danger in the amygdala and striatum of
      the mouse.
AB  - The ability to identify, develop, and exploit conditions of safety and security
      is central to survival and mental health, but little is known of the neurobiology
      of these processes or associated positive modulations of affective state. We
      studied electrophysiological and affective correlates of learned safety by
      negatively correlating an auditory conditioned stimulus (CS) with aversive events
      (US). This CS came to signify a period of protection, reducing fear responses to
      predictors of the US and increasing adventurous exploration of a novel
      environment. In nonaversive conditions, mice turn on the CS when given the
      opportunity. Thus, conditioned safety involves a reduction of learned and
      instinctive fear, as well as positive affective responses. Concurrent
      electrophysiological measurements identified a safety learning-induced long
      lasting depression of CS-evoked activity in the lateral nucleus of the amygdala,
      consistent with fear reduction, and an increase of CS-evoked activity in a region
      of the striatum involved in positive affect, euphoric responses, and reward.

PMID- 15848809
TI  - Rapid associative encoding in basolateral amygdala depends on connections with
      orbitofrontal cortex.
AB  - Certain goal-directed behaviors depend upon interactions between basolateral
      amygdala (ABL) and orbitofrontal cortex (OFC). Here we describe
      neurophysiological evidence of this cooperative function. We recorded from ABL in
      intact and OFC-lesioned rats during learning of odor discrimination problems and
      reversals. During learning, rats with ipsilateral OFC lesions exhibited a marked
      decline in the proportion of ABL neurons that fired differentially during cue
      sampling both before and after reversal and in the proportion of neurons that
      reversed odor preference when the odor-outcome associations were reversed. This
      decline appeared to reflect a loss of rapid flexibility in cue selectivity that
      characterized activity in intact rats. In addition, lesioned rats had fewer
      neurons that fired in anticipation of the predicted outcome during a delay period
      after responding but before outcome delivery. These findings support a role for
      OFC in facilitating the encoding of information about expected outcomes in ABL.

PMID- 15848810
TI  - Does neuronal synchrony underlie visual feature grouping?
AB  - Previous research suggests that synchronous neural activity underlies perceptual
      grouping of visual image features. The generality of this mechanism is unclear,
      however, as previous studies have focused on pairs of neurons with overlapping or
      collinear receptive fields. By sampling more broadly and employing stimuli that
      contain partially occluded objects, we have conducted a more incisive test of the
      binding by synchrony hypothesis in area MT. We find that synchrony in spiking
      activity shows little dependence on feature grouping, whereas gamma band
      synchrony in field potentials can be significantly stronger when features are
      grouped. However, these changes in gamma band synchrony are small relative to the
      variability of synchrony across recording sites and do not provide a robust
      population signal for feature grouping. Moreover, these effects are reduced when
      stimulus differences nearby the receptive fields are eliminated using partial
      occlusion. Our findings suggest that synchrony does not constitute a general
      mechanism of visual feature binding.

PMID- 15848811
TI  - Cortical local field potential encodes movement intentions in the posterior
      parietal cortex.
AB  - The cortical local field potential (LFP) is a summation signal of excitatory and
      inhibitory dendritic potentials that has recently become of increasing interest.
      We report that LFP signals in the parietal reach region (PRR) of the posterior
      parietal cortex of macaque monkeys have temporal structure that varies with the
      type of planned or executed motor behavior. LFP signals from PRR provide better
      decode performance for reaches compared to saccades and have stronger coherency
      with simultaneously recorded spiking activity during the planning of reach
      movements than during saccade planning. LFP signals predict the animal's
      behavioral state (e.g., planning a reach or saccade) and the direction of the
      currently planned movement from single-trial information. This new evidence
      provides further support for a role of the parietal cortex in movement planning
      and the potential application of LFP signals for a brain-machine interface.

PMID- 15848815
TI  - Students' perceptions of educational environment: a comparison of academic
      achievers and under-achievers at kasturba medical college, India.
AB  - CONTEXT: No country, least of all poorly resourced countries such as India, can
      afford to lose too many medical students in their undergraduate years. It would
      be useful to have an instrument to identify those students who are vulnerable to
      academic failure at this level of training and to identify the features of the
      educational environment that they perceive differently from students who are
      succeeding academically in order to design intervention strategies. Gender
      differences in perceptions of the educational environment might well emerge in
      particular academic or cultural contexts, with particular curricula. The present
      study was motivated by this concern and focused on comparisons between academic
      achievers and under-achievers and male and female students of Kasturba Medical
      College, India. OBJECTIVES: (1) To compare the perceptions of the educational
      environment of academic achievers and under-achievers and to identify problem
      areas that should be remediated. (2) To identify whether there is any gender
      difference in the perceptions. METHODS: The Dundee Ready Educational Environment
      Measure (DREEM) was administered to 508 medical students studying in the clinical
      years at the Kasturba Medical College in India. Item as well as scale scores were
      compared between academic achievers and under-achievers. FINDINGS: Overall sample
      of the present study rated educational environment in this institution as
      average. The overall mean DREEM score was significantly higher for academic
      achievers. Compared to under-achievers, academic achievers scored significantly
      higher on perceptions regarding teachers, academic atmosphere and social self
      perceptions. In addition to this, the overall rating (total DREEM score) of
      female students was significantly less compared to males in the academically
      vulnerable group. CONCLUSIONS: Perceptions of poor performers are significantly
      different from those of better performers in the same institution. More
      importance should be given to the perceptions of students to improve the
      educational environment, as perceptions are associated positively with learning
      outcome, learning approach and attitude toward studying. Use of the DREEM as a
      monitoring tool might permit timely interventions to remediate problematic
      educational environments.

PMID- 15848816
TI  - Core curriculum and special study modules at the Faculty of Medicine and Health
      Sciences, Universiti Malaysia Sarawak.
AB  - INTRODUCTION: The Faculty of Medicine and Health Sciences (FMHS), follows a
      problem-based learning, integrated and community-based curriculum which reflects
      the specific needs of doctors working in Sarawak. Using paediatrics as an
      example, this paper describes the process of development of core content
      (knowledge, procedural and communication skills, attitudes), additional knowledge
      and special study modules at the FMHS. OBJECTIVES: In 2003, the Department of
      Paediatrics and Child Health conducted a workshop to evaluate and update its 5
      year-old curriculum. METHODS: The wise-men approach was adopted. Local and guest
      academicians (including members of the Department of Community Medicine and Basic
      Health Sciences), consultants, registrar, house officer and nursing staff of the
      Paediatric Department of Sarawak General Hospital (SGH), paediatric nursing
      lecturer and members of Medical Education Unit were involved. The review was
      based on three approaches: Problem/Task-based learning; Spiral curriculum;
      Outcome-based education. RESULTS: Core content and additional knowledge topics
      were modified. The special study modules were retained, but their duration was
      reduced. It was recommended that the curriculum should be reviewed at regular
      intervals. DISCUSSION: To select the core content and additional knowledge
      topics, clear and specific criteria were developed. Some topics were dropped,
      others were added, and some were moved from core to the additional knowledge
      section. CONCLUSION: It was a rewarding activity. The reviewed curriculum was
      received well by both the students and faculty. The enthusiasm and cooperation
      extended, especially by the faculty at SGH in the implementation of this
      curriculum, was remarkable.

PMID- 15848817
TI  - The school, a viable educational site for interdisciplinary health promotion.
AB  - BACKGROUND: An interdisciplinary health promotion module, using the community
      based teaching approach, is offered by the University of the Western Cape (UWC).
      Schools in Delft, a poor socio-economic area with high unemployment, crime and a
      range of social problems, are used as the teaching site. AIM: To assess the
      status of the health promotion initiatives in schools where students were placed.
      METHOD: A self-administered structured questionnaire for teachers and principals.
      Variables included were demographic data, views of health promotion, health
      promotion activities at the school, barriers and opportunities to implement
      health promotion activities. RESULTS: A response rate of 68.75 % (n = 55) for
      teachers and 100 % (n = 4) for principals was obtained. Most (87%) teachers felt
      that health promotion has a place within the curriculum. They reportedly focused
      on topics related to health within the school curriculum. Partners, such as
      public health nurses, university students, and a pharmaceutical company, offer
      additional health promotion initiatives. These include general health checks,
      HIV/AIDS information, adolescent health and dental health. Barriers to initiate
      and sustain programmes include lack of resources, insufficient staff training,
      lack of commitment by both teaching staff and the community, insufficient time,
      the heavy workload of teachers, and communication problems as a result of
      language barriers. Only 36% of teachers felt the school environment was conducive
      to learning. CONCLUSION: Health promotion initiatives in the schools concerned
      are uncoordinated, erratic, based on the resources that the school has access to
      at a given time and the demands of the curriculum.

PMID- 15848818
TI  - Applying service-learning through a community-academic partnership: depression
      screening at a federally funded community health center.
AB  - CONTEXT: Increasingly, health care facilities worldwide, particularly those that
      comprise the safety-net, are finding themselves understaffed and challenged to
      meet patients' needs. Identifying additional sources of support and resources is
      critical for facilities to be able to sustain current and develop new initiatives
      to improve patients' health. APPROACH: We present one community health center's
      reliance on a partnership with an academic medical/nursing institution to develop
      and initiate a depression screening and treatment project. Incorporating students
      to help implement or pilot a needed clinical service for a high prevalence
      condition presents significant rewards as well as challenges. Nevertheless, an
      academic-community partnership has the potential to initiate systems change at
      the clinical level. RESULTS: Using a service-learning modality, medical and
      nursing students worked with health center providers to initiate a pilot
      depression screening and treatment program based on the chronic disease model.
      Implementation of this initiative succeeded in poising the health center for
      participation in a large, federally supported collaborative on depression in
      primary care. While students gained insight into some of the challenges faced by
      safety net providers and their patients, discontinuity in student availability
      led to uneven pacing in project implementation. CONCLUSION: Curricula that employ
      a service-learning framework can enable health care facilities world-wide to gain
      additional resources for needed initiatives. Students' learning experiences can
      provide an excellent mutually beneficial opportunity as a "jumpstart" for new
      evidence-based clinical initiatives and demonstration projects. Such programs can
      help meet the needs of patients while enhancing students' education. However,
      students can neither make up for staffing shortages nor be expected to maintain
      programs. In order to be successful for the long term, service-learning projects
      must skirt the pitfalls of the inherent logistical incompatibilities e.g.
      schedules and length of commitment, between academic institutions and health care
      facilities.

PMID- 15848819
TI  - Junior doctors' opinions about the transition from medical school to clinical
      practice: a change of environment.
AB  - INTRODUCTION: Concerns have been growing about the effects of the working
      environment on junior doctors and the learning opportunities available to them.
      In order to identify problems and opportunities for improvement, we explored
      junior doctors' opinions about the transition from student to practitioner.
      METHOD: Seventeen recent graduates in four focus groups discussed the transition.
      DATA ANALYSIS: Related comments were combined in the report of the discussions,
      which was approved by the participants. RESULTS: The transition was perceived as
      a major change, particularly the increased responsibility and workload and
      contacts with other health care workers and patients. Preparation during
      undergraduate training was adequate as regards knowledge, communication, history
      taking and physical examination skills but not for pharmacological knowledge and
      patient management skills. Problems were connected with practical procedures and
      feelings of uncertainty. There was little formal education. Proposals to ease the
      transition were earlier patient contacts, more involvement in patient management
      and growing responsibility during clerkships. DISCUSSION: Although the sample was
      small, the uniform opinion in all groups supports the validity of the findings.
      Junior doctors felt confident with regard to knowledge and skills, but
      experienced difficulties with patient management, practical matters and their
      role on the team. Contrary to the idea of an educational continuum, formal
      learning appeared to be very limited in the hospital environment. CONCLUSIONS:
      Preparation for medical practice may benefit from active involvement of clerks in
      patient management decisions and a gradual increase in responsibilities. An
      effective medical education continuum would require more attention for house
      officers' learning.

PMID- 15848820
TI  - Need for strengthening of internship (rotatory housemanship) training in India.
AB  - INTRODUCTION: Internship is a problematic phase in the training of doctors in
      India. At the end of their one-year Internship, students are not formally
      examined for proficiency, rarely a student is not given a satisfactory completion
      certificate and training is sometimes not supervised. Students are required to
      spend three months of this Internship in Primary Health Centres at rural
      postings. During this period the students often prepare for the written exams
      that would allow them to pursue post-graduate studies. METHOD: In a personal
      reflection, this situation is described in the current article. The author
      suggests several approaches to improve this unwanted situation, so that the rural
      postings could be taken more seriously by the students. OUTCOMES: Suggestions
      range from a post-internship examination, via the introduction of compulsory
      rural postings after graduation to an increase of the avenues for post-graduate
      training to include a course in family medicine and general practice.
      CONCLUSIONS: The objective of providing excellent training during internship
      periods cannot be achieved unless interns actively participate. If the current
      situation does not change, for example according to the suggested solutions, this
      valuable component of medical training will remain problematic, thereby hindering
      the optimal preparation of doctors for the entire spectrum of necessary health
      care in India.

PMID- 15848821
TI  - The self-perceived role and educational needs of pharmaceutical representatives:
      a survey.
AB  - INTRODUCTION: Despite considerable debate in the medical literature about the
      educational utility of pharmaceutical representatives (PR), little is known about
      their attitudes towards their role as marketers and/or educators, their ability
      to provide comprehensive information about products and their learning needs.
      DESIGN: A survey. SUBJECTS AND METHOD: Questionnaires were mailed to 606 PRs from
      five Canadian pharmaceutical companies. RESULTS: Of 309 (51%) respondents, 98%
      strongly agreed or agreed they had a role in educating doctors, while 52%
      strongly disagreed or disagreed their main goal was marketing. Overall, 92%
      agreed they had received adequate training to perform a well-informed detail, and
      96% reported the information they provide is accurate. The majority (66%) felt a
      university-accredited program would improve the quality of their detailing.
      CONCLUSION: Most PRs believe their main goal is education. Despite most reporting
      that they had received adequate training, they felt that a university-accredited
      educational program would improve the quality of detailing. The number of years
      that a PR spent in the industry appears to have an effect on how they perceive
      their role.

PMID- 15848822
TI  - Students, stress and coping strategies: a case of Pakistani medical school.
AB  - OBJECTIVE: Assess the perception of stress amongst medical students and their
      coping strategies. METHODOLOGY/STUDY DESIGN: A cross sectional study using a semi
      structured self administered questionnaire was carried out over four weeks, using
      a small sample of students of all categories and classes of a medical college.
      RESULTS: A total of 264 students out of 300 (88%) filled in the questionnaire.
      Inability to cope, helplessness, increased psychological pressure, mental tension
      and too much workload are 'stress factors' for students. A considerable majority
      (> 90%) think that they have been stressed at one time or another. Ninety-four
      per cent of males have experienced stress. The senior students of the fourth and
      final year feel more stressed (95% and 98% respectively). Low moods, inability to
      concentrate, loss of temper are most common symptoms. Females report more
      symptoms. Academics and exams are the most powerful stressors. Sports, music,
      hanging out with friends, sleeping or going into isolation are various coping
      mechanisms. Stress can affect the academic performance. If needed, students
      prefer to talk to a peer. They demand more recreational activities on campus,
      revised schedule of academics and exams, better counselling facilities and
      improvement in student-teacher relationship. CONCLUSION: The prevalence of
      perceived stress seems to be high among medical students, which tends to affect
      not only their academic performances but also all aspects of health. Review of
      academics and exam schedules, more leisure time activities, better interaction
      with the faculty and proper guidance, advisory services and peer counselling at
      the campus could do a lot to reduce the stress.

PMID- 15848823
TI  - Medical and nursing students' knowledge and attitudes toward violence against
      women in India.
AB  - OBJECTIVE: The purpose of this study was to explore the knowledge and attitudes
      towards violence against women among fourth (final) year baccalaureate nursing
      students and fifth (final) year medical students from two distinct educational
      institutions in India. METHODS: Data were collected from 440 students using two
      questionnaires: the Student Exposure to Woman Abuse Questionnaire (SEWAQ), and
      the Inventory of Beliefs about Wife Beating (IBWB). Results were analysed based
      on gender, profession, and educational institution. FINDINGS: Nursing students
      believed that they had received more classroom preparation and practical skills
      to better prepare them to assist abused clients than male and female medical
      students. Only 38% of the participants believed that they had acquired classroom
      knowledge on woman abuse through their respective educational programs, whereas
      43% thought they had practical skills to care for victims. All participants were
      sympathetic toward abuse victims, but demonstrated varying attitudes about the
      justification for abuse against women, help given to victims, punishment of the
      offender and the effect of woman abuse. Female medical students believed more
      strongly than males and nursing students that wives do not gain from being
      beaten. CONCLUSIONS: Congruent with existing literature, the study demonstrated
      that health care students in India do not receive sufficient training, practical
      skills and classroom knowledge to effectively manage abuse against women.

PMID- 15848824
TI  - Problem-based learning in public health instruction: a pilot study of an online
      simulation as a problem-based learning approach.
AB  - Although increasingly used as a modality in medical education, Problem-Based
      Learning (PBL) remains somewhat overlooked in the training of public health
      students (Pham & Blumberg, 2000). This project involved a pilot test of a web
      based community simulation as a PBL platform in an undergraduate health behavior
      course. PURPOSE: To develop and pilot test a web-based computer simulation as an
      implementation of problem-based learning in an undergraduate public health
      behavior course. METHOD: Using a web-based simulation platform, a virtual
      community was designed in which the effects of a mock infectious disease outbreak
      could be studied and various interventions could be tested. Upon completion of
      the semester course, 14 undergraduate public health education students completed
      a survey and participated in a focus group to determine issues related to the
      simulation. Research focused on whether the simulation was perceived as
      motivating and which aspects were found to be confusing, ineffective or
      unrealistic. FINDINGS: Results of the study suggested that a PBL experience based
      on a community simulation may be effective in providing a motivating and
      interesting PBL tool for instructing undergraduate public health students. A
      majority of students agreed that the experience was more motivating and
      interesting than a more traditional assignment. Design recommendations include an
      emphasis on incorporating a rich multimedia background, realistic communication
      and project management tools and the capability for students to submit formatted
      documents. Further study of attitudinal differences and attainment of learning
      objectives is recommended between students participating in the simulation
      experience and those engaging in a traditional assignment.

PMID- 15848825
TI  - Making medical research clinically friendly: a communication-based conceptual
      framework.
AB  - CONTEXT: It often takes a long time before the results of medical research are
      actually used by health care practitioners in day-to-day clinical settings. This
      problem, referred to as "the evidence-to-practice gap", has significant
      implications for patient health care. Practitioners have difficulty keeping up
      with the latest information in part because it is reported in hundreds of
      journals that may not be easily accessed and understood. APPROACH: This essay
      conceptualizes the evidence-to-practice gap as a communication problem and
      suggests how academic research can be translated into messages that are easier
      for practitioners to access, comprehend and incorporate into their medical
      practice. A "translation framework" shows the importance of targeting messages to
      specific audiences and provides a communication-based conceptual approach for
      summarizing research for clinicians. PRACTICAL IMPLICATIONS: Targeting the
      results of academic research to practitioners will decrease the time it takes for
      patients to benefit from the latest medical evidence. Translation guidelines can
      help health researchers write more effectively for both academic and practitioner
      audiences. Since the evidence-to-practice gap is a systemic problem that begins
      with how we train our health researchers, educators should consider addressing
      this topic in the health professions classroom. The framework presented here can
      serve as the basis for an instructional unit on interpreting and reporting
      research findings. Finally, information technology can play a much larger role in
      the communication process because of the enormous advantages of quick access and
      data organization that computers and the Internet provide. Practitioner-targeted
      research summaries could be made available on government or not-for-profit
      sponsored websites as well as by journals themselves. Funding opportunities exist
      for research that focuses on how technology can help improve health care, and so
      the time is right for health researchers to investigate ways of making their
      studies more accessible and quickly usable via web-based distribution. The
      potential of medical science should not be limited by an information delivery
      system that we have the knowledge, expertise and resources to improve.

PMID- 15848826
TI  - Experiencing service learning: students of a new medical school as vaccinators
      and independent monitors.

PMID- 15848827
TI  - An interview of Maria Elena Ceballos Velasquez.

PMID- 15848828
TI  - An interview of Thelma John.

PMID- 15848830
TI  - Position paper on multiprofessional education.

PMID- 15848831
TI  - Clinical teaching.

PMID- 15848901
TI  - First things first.

PMID- 15848902
TI  - The pathology of ionizing radiation as defined by morphologic patterns.
AB  - This article presents a brief description of the effects of ionizing radiation in
      human tissues, as seen by the Pathologist. The lesions that occur in multiple
      organ/tissues will be discussed, dividing them into those that affect (a) the
      parenchyma or epithelia, (b) the stromal elements, and (c) the blood vessels.
      Since not all lesions fit into these patterns, the exceptions will be described
      as characteristic organ lesions. Unless specified otherwise the alterations
      presented are those that result from electromagnetic radiation (x-rays and gamma
      rays) as used for clinical radiation therapy. Most of the material presented will
      be delayed injury (i.e. months-to-years after exposure). The
      epithelial/parenchymal lesions include atrophy, necrosis, metaplasia, cellular
      atypia, dysplasia, and neoplasia. The common stromal lesions--the best recognized
      by pathologists--include fibrosis, fibrinous exudates, necrosis (with a paucity
      of cellular inflammatory exudates), and atypical fibroblasts. The vascular
      lesions are quite consistent: most often they affect the microvessels
      (capillaries, sinusoids) producing lethal and sublethal damage to the endothelial
      cells, with capillary rupture or thrombosis. Medium-size vessels show neointimal
      proliferation, fibrinoid necrosis, thrombosis, or acute arteritis. Damage in
      large vessels is less common; it occurs more in arteries than in veins and
      includes neointimal proliferation, atheromatosis, thrombosis and rupture (a
      dramatic complication). Some of the characteristic organ lesions are veno
      occlusive liver disease, acute radiation pneumonitis, permanent bone marrow
      hypoplasia or aplasia, and colitis cystica profunda. Neoplasms are a well
      recognized delayed complication of radiation and will not be described in detail.
      It is important to remember that there are no pathognomonic features of injuries
      produced by ionizing radiation. Nonetheless, although not specific individually,
      the combined features are characteristic enough to be recognized.

PMID- 15848903
TI  - Aromatase inhibitors in the treatment of early and advanced breast cancer.
AB  - The third generation aromatase inhibitors anastrozole, exemestane, and letrozole
      have been compared with tamoxifen and other endocrine therapies in several
      studies in early and advanced breast cancer. These studies are reviewed in this
      report. Based on the available evidence, the panel recommends that adjuvant
      treatment with tamoxifen for 5 years should no longer be considered as the sole
      standard but that a third-generation aromatase inhibitor should be used either
      alone or in a sequence with tamoxifen in the adjuvant treatment of postmenopausal
      women with hormone-receptor-positive breast cancer. Third generation aromatase
      inhibitors may be considered as the first line therapy of hormone-receptor
      positive advanced breast cancer in postmenopausal women, and they may also be
      used for preoperative therapy of breast cancer.

PMID- 15848904
TI  - Gene expression in midgut carcinoid tumors: potential targets for immunotherapy.
AB  - Classical midgut carcinoids are serotonin-secreting tumors derived from
      enterochromaffin cells in the gut. Metastatic disease represents a therapeutic
      challenge and immunotherapy implies a novel approach for treatment. In order to
      define antigens suitable for T-cell therapy with a preferential expression in
      midgut carcinoid tissue a broad screening of genes with preferential
      neuroendocrine restriction, genes described as over-expressed in various
      malignancies, and genes encoding cancer-testis associated antigens was performed.
      The expression of 32 genes was analyzed by reverse transcription polymerase chain
      reaction (RT-PCR) in 28 midgut carcinoid specimens, in the cell line BON and in
      normal tissues. Immunohistochemistry (IHC) was used to evaluate protein
      expression. Expression is shown of genes that have previously not been observed
      in midgut carcinoid tumors, such as Survivin and GAGEs. Also the expression is
      confirmed of genes that encode pivotal proteins in enterochromaffin cells, such
      as TPH1 and VMAT1, and their tissue-restricted expression is indicated. In
      addition, gene expression of IA-2 and CDX-2 in normal gastrointestinal (GI) tract
      and in tumor is shown. Protein expression of TPH, VMAT1, and Survivin was
      detected in tumor tissue. This study elucidates that TPH1, VMAT1, and Survivin
      should be further investigated as potential target antigens for T cell-mediated
      immunotherapy of midgut carcinoids.

PMID- 15848905
TI  - Ductal carcinoma in situ of the breast with different histopathological grades
      and corresponding new breast tumour events: analysis of loss of heterozygosity.
AB  - To compare chromosomal alterations in ductal carcinoma in situ (DCIS) of
      different histopathological grades and to study aberrations between primary DCIS
      and corresponding ipsi- or contralateral new in situ or invasive tumours, a study
      was undertaken of the pattern of loss of heterozygosity (LOH) at chromosomal
      regions in which LOH has previously been described in invasive breast cancer. LOH
      was analysed using 19 microsatellite markers located on chromosomes 3p, 6q, 8p,
      8q, 9p, 11p, 11q, 16q, 17p, and 17q in 30 women with a primary DCIS. Eleven women
      with DCIS of grade 1 and 19 with grade 3 according to the EORTC classification
      system were included. In six patients LOH was also analysed in a subsequent new
      breast cancer. Fractional allelic loss (FAL, the ratio of chromosomal arms where
      allelic loss was detected divided by the total number of chromosomal arms with
      informative markers) was statistically significantly higher in grade 1 DCIS
      compared with grade 3 (p=0.02) for the 19 loci, indicating that the amount of
      allelic loss does not correlate with increasing aggressiveness of the studied
      tumours. Also observed was a complete heterogeneity of LOH in the primary DCIS
      and their corresponding new events, suggesting that these events probably
      developed from genetically divergent clones.

PMID- 15848906
TI  - The role of epidermal growth factor receptor and E-cadherin for the outcome of
      reduction in the overall treatment time of radiotherapy of supraglottic larynx
      squamous cell carcinoma.
AB  - Reduction of the overall treatment time (OTT) of radiotherapy results in
      increased T-site control in squamous cell carcinomas of the head and neck
      (HNSCC). However, the response is heterogeneous and accelerated repopulation of
      clonogenic tumour cells during therapy may be one of the factors determining this
      response. The aim of the present study was to identify the influence of the
      epidermal growth factor receptor (EGFr) and E-cadherin for T-site control when
      the OTT was reduced and whether the markers add information to the
      histopathological grading in selecting patients for accelerated radiotherapy. A
      total of 209 patients from randomized DAHANCA-trials with supraglottic larynx
      squamous cell carcinomas treated with primary radiotherapy with different OTT of
      9(1/2), 6(1/2), and 5(1/2) weeks. Available formalin-fixed paraffin embedded
      tumour tissues were re-evaluated for histopathological characteristics and
      stained for EGFr and E-cadherin. Data were correlated with patient and tumour
      characteristics and 5-year T-site control. EGFr and E-cadherin were not
      associated with patient or tumour characteristics except that EGFr correlated to
      carcinomas with a well to moderate histopathological feature. Tumours with high
      EGFr or low E-cadherin did benefit from reduced OTT, and the combination of the
      two (high EGFr and low E-cadherin) had the most significant acceleration of
      treatment effect, compared with tumours with other combinations of EGFr and E
      cadherin expression. Tumours with high expression of EGFr and low expression of E
      cadherin showed the most significant increase in T-site control when the overall
      treatment time of radiotherapy was reduced, and the markers may be useful for
      selecting patients who will benefit from accelerated radiotherapy.

PMID- 15848907
TI  - Head and neck cancer in the elderly: a cohort study in 40 patients.
AB  - INTRODUCTION: In the industrialized nations of the Western hemisphere the age
      group beyond 75 years will grow steadily, requiring special attention by medical
      professionals in the future. With regard to these expectations 40 patients,
      beyond the age of 75 and who were first diagnosed to suffer from squamous cell
      carcinoma of the upper aerodigestive tract, were analysed. MATERIAL AND METHODS:
      Forty patients diagnosed and treated between 1998 and 2003 for head and neck
      squamous cell carcinoma (HNSCC) were analysed. RESULTS: Laryngeal carcinoma was
      noted in 80% of the patients. All types of treatment were tolerated well. Patient
      compliance was generally good and the rate of complications was low. CONCLUSION:
      The results of the present study show that HNSCC in elderly patients should be
      treated with curative intention. Age itself should never be a sole factor in
      deciding which curative therapy should be undertaken. Exceptions could be made in
      patients with severe general comorbidity.

PMID- 15848908
TI  - Quality of treatment in routine care in a population sample of rectal cancer
      patients.
AB  - Variations in compliance with rectal cancer treatment guidelines and the effect
      of quality indicators on long-term outcomes were investigated with data from the
      Munich Cancer Registry. Patients diagnosed between 1996 and 1998 with an invasive
      primary rectal tumor which was resected were included in these analyses (n=884).
      Median follow up was 5.7 years. Relative and overall survival was examined.
      Adjusted survival was predicted by UICC stage, grade, age, local recurrence, and
      residual tumor status. UICC III patients receiving the recommended adjuvant
      therapy had a significant survival advantage in the multivariate model; UICC II
      patients did not. Even if there were no significant survival differences there
      were significant treatment and outcome (regarding local recurrence) variations
      between hospitals. The variations between hospitals refer to different quality
      indicators in the individual hospitals. The outcome (regarding survival) appears
      good in Munich and is comparable with other population studies. Fewer local
      recurrences, better reporting of the TME technique, greater use of combined
      therapy and fewer stomas, however, may improve the quality of care in Munich.
      Variations in care between hospitals should therefore be monitored and
      controlled. Detailed and frequent feedback to the clinicians is vital to improve
      quality of care and is possible with cancer registries.

PMID- 15848909
TI  - Absence of prognostic significance of p21(WAF1/CIP1) protein expression in non
      small cell lung cancer.
AB  - Prognostic value of p21WAF1/CIP1 expression in non-small-cell lung cancer
      patients (NSCLC) remains unclear. In this study the authors investigated the
      clinical significance of p21WAF1/CIP1 expression in a group of 117 NSCLC
      patients, who underwent curative pulmonary resection. Expression of p21WAF1/CIP1
      protein was assessed immunohistochemically and samples showing>5% of positive
      tumor cells were considered positive. Seventy-six samples (65%) showed positive
      nuclear p21WAF1/CIP1 protein expression. There was no relationship between the
      expression of p21WAF1/CIP1 protein and major clinico-pathological factors, and
      neither there was an impact of p21WAF1/CIP1 protein expression on disease-free
      and overall survival. p21WAF1/CIP1 protein occurrence was not correlated with
      previously determined p53 protein expression and there was also no relationship
      between all possible p21WAF1/CIP1/p53 phenotypes and survival. In uni- and
      multivariate analysis only stage of disease was independent prognostic factors.
      These results suggest the lack of prognostic relevance of p21WAF1/CIP1 expression
      (analyzed separately or jointly with p53 protein) in surgically treated NSCLC
      patients.

PMID- 15848910
TI  - Adjuvant clodronate in breast cancer.

PMID- 15848912
TI  - Toxicity and compliance with a chemoradiotherapy schedule for advanced
      nasopharyngeal carcinoma: a single institution experience using the Intergroup
      0099 study regimen.

PMID- 15848915
TI  - Access to vision care in an urban low-income multiethnic population.
AB  - OBJECTIVE: This study applied a well-known, recently revised theoretical model of
      healthcare access and utilization, the Behavioral Model for Vulnerable
      Populations, to examine the relationship between access to care and utilization
      of eye care services among a multiethnic, predominately minority sample of
      residents from low-income public housing. DESIGN: Population-based, cross
      sectional survey of community sample. SETTING: Urban Public Housing Communities
      in Los Angeles County, California. PARTICIPANTS: A geographically defined
      stratified random sample of 152 residents (86% Latino or African American) 40
      years of age and older from three urban public housing communities. RESULTS: Only
      62% of our sample of persons 40 years and older had received an eye examination
      within the past 2 years. Sixty-one percent of participants reported having vision
      care coverage. Yet, one out of four respondents claimed that no health care
      provider had ever told them that they needed an eye-examination. Applying
      multiple logistic regression and controlling for a number of predisposing,
      enabling, and need-for-care characteristics, the variables 1) receiving advice
      from health care providers for eye examination (OR = 3.9, p < 0.01), 2)
      possessing coverage for eye-care (OR = 3.2, p < 0.01), and 3) having regular and
      continuity of medical care (OR = 2.4, p < 0.01) remained significant predictors
      of eye-examination within the past 2 years. CONCLUSION: This study documents
      significantly diminished utilization of eye care services relative to recommended
      guidelines for a low-income, predominately minority sample of residents from
      public housing communities. We documented no association between presence of
      diabetes or hypertension and recency of eye examination. Affordability,
      continuity, and regular sources of care, as well as receiving physician advice,
      remain the core factors significantly associated with receiving vision care.
      These results underscore the need for continued efforts to ensure that the
      medically underserved minority have access to vision care services. These
      findings also point toward the urgent need for educational and motivational
      interventions that encourage health care providers serving underserved
      communities to promote eye examination, particularly among diabetic patients,
      hypertensive patients, and other individuals at risk for eye-related disease and
      complications.

PMID- 15848916
TI  - Visual impairment and morbidity in community-residing adults: the national health
      interview survey 1986-1996.
AB  - PURPOSE: To examine the association between visual impairment (VI) and morbidity.
      METHODS: Using pooled, annual population-based household interview survey data (n
      = 140,366) from the 1986-1996 National Health Interview Survey, covariate
      adjusted, gender and age group specific logistic regression analyses were used to
      examine associations between VI and five morbidity indicators: restricted
      activity days, bed rest days, doctor visits, hospitalizations, and self-rated
      health. RESULTS: After controlling for educational status, race and the number of
      reported non-ocular health conditions, fair or poor health status (compared to
      excellent, very good, or good health status) was generally more strongly
      associated with severe, bilateral VI (range of odds ratios [OR's]: 2.14-7.24)
      than with some VI (OR's: 1.45-2.21). Severe, bilateral VI was also associated
      with more frequent doctor and hospital visits among adults 18-64 years of age
      (range of OR's: 1.69-3.34), and restricted activity and bed rest days among males
      45 years and older (range of OR's: 1.95-3.69). CONCLUSIONS: The present findings,
      in conjunction with other studies documenting the impact of VI on morbidity
      outcomes, indicate that an increased focus on the provision of eye care services
      will be necessary to address the growing burden of VI in aging societies.

PMID- 15848917
TI  - Prevalence and causes of blindness and low vision in a rural setting in Pakistan.
AB  - PURPOSE: To determine the prevalence and causes of blindness and visual
      impairment in people 40 years of age and older in Budni, Peshawar, Pakistan.
      METHODS: A population-based cross-sectional study was carried out involving 1,106
      men and women 40 years of age and older in a rural area in Pakistan's North West
      Frontier Province (NWFP). All subjects with a presenting visual acuity < 6/18 in
      either eye were referred to a centralized clinic for a standardized eye
      examination that included refraction and dilated fundal examination. The main
      outcome was blindness (presenting visual acuity < 3/60 in the better eye) and low
      vision (presenting VA < 6/18-3/60 in the better eye). RESULTS: Of 1,106 people
      examined, 21 (1.9%; 95% CI: 1.1-2.7%) were blind, while another 27 (2.4%) and 62
      (5.5%) subjects had severe visual impairment (< 6/60-3/60) and visual impairment
      (< 6/18-6/60), respectively. Women, as compared to men, had a higher prevalence
      of visual impairment and severe visual impairment; but they had a lower
      prevalence of blindness (1.6 vs. 2.2%); however, the difference was not
      statistically significant (0.6%; 95% CI: -0.9-2.1%). Similarly farmers had the
      highest prevalence of blindness. The leading cause of blindness and low vision
      was cataract, which accounted for 14 of 21 (66.6%) cases of blindness and 49 of
      89 (55.5%) cases of low vision. The second leading cause of blindness was
      uncorrected aphakia. CONCLUSION: Much of the blindness was due to unoperated
      cataract and uncorrected aphakia. Thus, there is an urgent need to develop ways
      in which cataract surgical output could be increased, and glasses provided to
      those who need them.

PMID- 15848918
TI  - The prevalence of strabismus and amblyopia in Japanese elementary school
      children.
AB  - BACKGROUND: The purpose of this study is to elucidate the prevalence of
      strabismus and amblyopia in a large population of Japanese elementary school
      children, from Grade 1 to Grade 6, ages ranging from 6 to 12 years. The School
      Health Law requires that all pupils in Grade 1 to Grade 6 be examined for vision
      and eye problems. Visual acuity testing is done by school teachers and eye
      disease screening by school ophthalmologists. Pupils with suspected ocular
      diseases are further examined by extramural ophthalmologists and the results
      reported back to the schools. The schools then summarize and send uncorrected
      visual acuity and ocular disease incidence, together with other health
      statistics, to the municipal education committees. The data are forwarded to the
      Prefecture Governments and finally submitted to the Education Ministry of the
      Central Government. Both the Prefecture Governments and the Education Ministry
      publicize the school health statistics on their websites. The prevalence of
      strabismus and amblyopia remains unknown from these data because both diagnoses
      are included under the heading, eye diseases. METHODS: Questionnaires asking
      about the numbers of children with different types of strabismus and amblyopia
      were sent to all elementary schools in Okayama Prefecture and the results were
      summarized. RESULTS: The number of children covered by the return of
      questionnaires was 86,531 (76.4%) of 113,254 total pupils in Grade 1 to Grade 6
      in Okayama Prefecture in the year 2003. The total numbers of children with
      strabismus and amblyopia were 1,112 (1.28%) and 125 (0.14%), respectively. The
      numbers of children with any type of exotropia and any type of esotropia were 602
      (0.69%) and 245 (0.28%), respectively. The major types of strabismus and
      amblyopia were intermittent exotropia in 109 children (0.12%), accommodative
      esotropia in 19 children (0.02%), anisometropic amblyopia in 23 children (0.03%),
      and ametropic amblyopia in 12 children (0.01%). The number of children with
      strabismus of unknown type was 245 (0.28%) while the number of children with
      amblyopia of unknown type was 81 (0.09%). CONCLUSIONS: The prevalence rates of
      strabismus and amblyopia in this population of Japanese elementary school
      children were lower than those reported in Western countries. The
      exotropia/esotropia ratio were increased in comparison with past studies in
      Japan. The school eye doctors need to be more diligent in identifying and
      diagnosing various types of strabismus and amblyopia in order to contribute to
      the school vision screening program already in place in Japan

PMID- 15848919
TI  - Hormone replacement therapy, reproductive factors, and age-related macular
      degeneration: the Salisbury Eye Evaluation Project.
AB  - PURPOSE: To evaluate a potential relationship between hormone replacement therapy
      (HRT), reproductive factors and age-related macular degeneration (AMD). METHODS:
      1,458 female participants (age 65-84) from the Salisbury Eye Evaluation study
      were available for this cross-sectional analysis. AMD outcomes were identified by
      reading center assessment of fundus photographs. RESULTS: Women who currently
      used HRT had a lower adjusted odds of large drusen (> 125 microm) (OR = 0.5, 95%
      CI 0.2-1.0). Use of HRT was not statistically significantly associated with the
      prevalence of early AMD or advanced AMD, although the odds ratios were all much
      less than 1. Women who had had an increased number of births had a greater
      prevalence of large drusen (test of linear trend, p = 0.03). CONCLUSIONS: Current
      use of HRT was associated with a lower odds of large drusen, which may be
      predictive of advanced AMD. No statistically significant correlations were found
      between HRT or reproductive factors and early or advanced AMD.

PMID- 15848920
TI  - Evaluation of the traveling vision examiner program in the submacular surgery
      trials pilot study.
AB  - PURPOSE: To describe methods and results and to assess the value of a Traveling
      Vision Examiner (TVE) Program designed to provide masked vision measurements by
      expert vision examiners who were independent of, and traveled to, local clinical
      centers. METHODS: The Submacular Surgery Trials (SST) Pilot Study was conducted
      to refine the design and methods for a set of multicenter, randomized clinical
      trials to evaluate submacular surgery in patients with subfoveal choroidal
      neovascularization (CNV) due to age-related macular degeneration (AMD) or ocular
      histoplasmosis (OHS), or idiopathic CNV in which the primary study outcome would
      be change in 2-year best-corrected vision from baseline. As part of the SST Pilot
      Study, the feasibility and value of a TVE Program was assessed. The goal of the
      program was to obtain unbiased vision measurements, according to a standard
      protocol, of best-corrected visual acuity, reading speed, and contrast threshold,
      of each patient at 2 and 4 years after enrollment. RESULTS: Eighty-three visits
      by TVEs were made to 16 centers participating in the SST Pilot Study; 239
      patients had at least one masked vision examination. Comparison of pairs of
      vision measurements of the traveling vision examiners and local vision examiners
      for 71 patients made on the same day showed good agreement overall (intraclass
      correlation coefficient > or = 0.81). CONCLUSIONS: The proposed TVE Program was
      judged to be a feasible and useful method of providing standardized, unbiased,
      masked vision measurements. This approach was incorporated into the larger
      clinical trials conducted by the SST Research Group.

PMID- 15848921
TI  - Methods for a population-based study of myopia and other eye conditions in school
      children: the Sydney Myopia Study.
AB  - PURPOSE: The Sydney Myopia Study will establish the prevalence of myopia and
      other eye diseases in a large representative sample of Sydney school children. It
      will also examine the relationship between myopia and potential modifiable risk
      factors and will assess potential gene-environment interactions by examining
      parents and siblings. METHODS: The target population is a stratified random
      cluster sample of 1750 Year 1 (age 6 years) and 1500 Year 7 (age 12 years)
      students from Sydney metropolitan schools. Procedures (comprehensive parent
      administered questionnaire and examination) involve standardized protocols to
      allow for comparison with international population-based data. Examinations
      include a detailed assessment of visual acuity, cover testing for strabismus,
      identification of amblyopia, slit-lamp examination, non-contact ocular biometry
      and cycloplegia (cyclopentolate) followed by autorefraction, optical coherence
      tomography, retinal thickness measurement, digital mydriatic retinal photography
      and aberrometry. CONCLUSIONS: The Sydney Myopia Study design and methodology will
      ensure valid findings on ocular development and health in a large representative
      sample of Sydney school children, for comparison with other population-based
      refraction data.

PMID- 15848949
TI  - Antibiotic exposure does not influence MRP2 functional expression in Caco-2
      cells.
AB  - Multidrug resistance-associated protein 2 (MRP2) is associated with active drug
      efflux and may influence oral bioavailability of common classes of drugs. MRP2
      expression demonstrates plasticity. Caco-2 cells, a routine in vitro model for
      predicting oral bioavailability, are often cultured in media containing
      antibiotics. We have investigated whether exposure of Caco-2 cells to two common
      antibiotic regimes alters MRP2 functional expression. Caco-2 cells were grown in
      the presence or absence of either gentamicin or penicillin-streptomycin for up to
      9 weeks. MRP2 functional activity was assessed by calcein efflux across the
      apical membrane. MRP2 protein expression was determined by immunoblots. Neither
      antibiotic regime resulted in consistent changes in calcein efflux across the
      apical membrane (reflecting MRP2 activity) or basolateral membrane (reflecting
      MRP3 and possibly MRP6 activity) of Caco-2 cells. MRP2 protein expression also
      showed no change in response to antibiotic exposure. Routine exposure of Caco-2
      cells to penicillin-streptomycin or gentamicin does not affect apical MRP2
      functional activity in intestinal enterocytic Caco-2 cells. Extrapolating these
      results to the situation in vivo suggests that the oral bioavailability of MRP
      substrates is not predicted to be influenced by recent courses of antibiotics.

PMID- 15848950
TI  - Phage display selection for cell-specific ligands: development of a screening
      procedure suitable for small tumor specimens.
AB  - Phage display technology has been widely used for developing tumor-targeting
      agents. Most of the efforts were directed towards identifying phage-displayed
      ligands against cancer-relevant purified targets and cancer cell lines. Whole
      cell screening procedures typically use a relatively large sample size and are
      not ideally suited for complex tumor tissues. We describe here a screening
      protocol that is suitable for non-adherent tumor cells from biopsy specimens. It
      requires only approximately 20,000 cells/round for biopanning and approximately
      10,000 cells/well for subsequent clone binding assessment by ELISA. We
      standardized the newly developed protocol using erbB2-overexpressing SKBR3 breast
      cancer cells and compared the results with conventional protocols employing about
      10-times more plate-adhered fixed or live cells. The selection rate of SKBR3
      binding clones from biopanning approximately 20,000 non-adherent SKBR3 cells by
      our filter cup protocol was comparable to that obtained from using approximately
      200,000 plate-adhered cells. Assessment of clones selected from different phage
      libraries showed that clones from fixed or live cells, adherent or non-adherent
      cells, either biopanned in filter cup or plate share specific motifs and binding
      properties. Some of the clones from each biopanning protocol bound to purified
      erbB2 and shared motifs with erbB family of receptors and their known ligands.
      These results demonstrated that the protocol developed in this study was capable
      of selecting cell-specific ligands using relatively small numbers of cells.
      Screening cells from a fresh human breast cancer specimen using our protocol
      showed enrichment of tumor binding clones at successive rounds of selection and
      some of the selected clones were tumor-specific in comparison to normal breast
      cells. These protocols have direct application to screen for tumor-binding
      ligands with small tumor tissue specimens.

PMID- 15848951
TI  - Physicochemical characteristics and in vivo deposition of liposome-encapsulated
      tea catechins by topical and intratumor administrations.
AB  - Tea polyphenols, including (+)-catechin, (-)-epicatechin, and (-)
      epigallocatechin-3-gallate (EGCG), have been shown to possess potent antioxidant
      and anticancer activities. The aim of this study was to evaluate the possibility
      of using liposomes for the local delivery, including skin and tumor deposition,
      of these polyphenols. Liposomes containing egg phosphatidylcholine, cholesterol,
      or anionic species were prepared by a solvent evaporation method and then were
      subjected to a probe sonicator. The size, zeta potential and entrapment
      efficiency of these liposomal formulations were determined to provide
      correlations with results from a subsequent in vivo study. The release rate study
      showed that inclusion of an anionic species, such as deoxycholic acid (DA) or
      dicetyl phosphate (DP), increased the permeability of the lipid bilayers, leading
      to the rapid release of these formulations. No significant increase in skin
      deposition of catechins was observed after topical application of liposomes. On
      the other hand, a greater amount of catechins were delivered into the solid tumor
      by liposomes than by the aqueous solution. The drug release rate and vesicle size
      of liposomes may influence drug deposition in tumor tissues. The isomers, (+)
      catechin and (-)-epicatechin, showed different physicochemical properties in
      liposomes and for local deposition in the skin and tumor. Finally, the presence
      of gallic acid ester in the structure of EGCG significantly increased the tissue
      uptake of catechins.

PMID- 15848952
TI  - Tetradecylmaltoside (TDM) enhances in vitro and in vivo intestinal absorption of
      enoxaparin, a low molecular weight heparin.
AB  - Tetradecylmaltoside (TDM) was evaluated as a potential gastrointestinal
      absorption enhancer for low molecular weight heparin (LMWH), enoxaparin. The in
      vitro efficacy of TDM (0.0625, 0.125 and 0.25% w/v) in enhancing transport of 3H
      enoxaparin or 14C-mannitol was investigated in human colonic epithelial cells
      (C2BBel). Metabolic stability of the drug was determined in C2BBel cell extracts.
      Transepithelial electrical resistance (TEER) was measured before and after
      exposure of the cells to TDM. Enoxaparin was further administered to anesthetized
      Sprague-Dawley rats in oral formulations in the absence or presence of increasing
      concentrations of TDM and drug absorption was monitored by measuring anti-factor
      Xa activity in rat blood. In vitro permeability study shows that apparent
      permeability (Papp) of 3H-enoxaparin across C2BBe1 cells was increased by 8-fold
      in the presence of 0.0625% TDM compared to untreated cells. The movement of 14C
      mannitol across the cell monolayer followed a similar pattern in the presence of
      increasing concentrations of TDM. No degradation or depolymerization of
      enoxaparin was observed when the drug was incubated in C2BBel cell extract. TEER
      was reversible after 60 min exposure of the cells to 0.0625% (w/v) TDM. Oral
      formulations of enoxaparin containing TDM administered to anesthetized rats
      significantly and rapidly increased gastrointestinal absorption as compared to
      those animals which received enoxaparin plus saline (p < 0.05). In the presence
      of 0.125% TDM in the formulation, enoxaparin oral bioavailability was increased
      by 2.5-fold compared to the saline control group. Overall, the data on the effect
      of TDM on the in vitro and in vivo intestinal permeation of enoxaparin suggest
      that TDM may represent a promising excipient for use in oral LMWH formulations.

PMID- 15848953
TI  - Enhanced gene transfer activity of peptide-targeted gene-delivery vectors.
AB  - We have evaluated the capacity of the cell-binding heptapeptide SIGYPLP to
      enhance transgene expression using non-viral and viral gene delivery vectors.
      Targeted polyplex based vectors showed good levels of DNA uptake in freshly
      isolated human umbilical vein endothelial cells (HUVECs) compared to untargeted
      controls, whilst displaying only modest increases in reporter gene activity. The
      targeted polyplexes showed reduced levels of DNA uptake in cells of a none
      endothelial origin although they mediated higher levels of transgene expression.
      The enhanced efficiency of transgene expression may relate to the more rapid rate
      of cell division. However, since in vivo application of polyplexes is compromised
      by instability to serum proteins, serum-resistant polyplexes (surface modified
      with multivalent reactive hydrophilic polymers based on poly[N-(2
      hydroxypropyl)methacrylamide] (pHPMA)) were also evaluated for their ability to
      mediate transgene expression. Surface modification of polyplexes with pHPMA
      ablates non-specific cell entry, reducing levels of transgene expression, whilst
      the incorporation of the SIGYPLP peptide into the hydrophilic polymer resulted in
      restored transgene expression in all formulations tested. The technology of
      surface modification using pHPMA can also be applied in the context of viruses,
      masking receptor-binding epitopes and enabling the linkage of novel cell
      targeting ligands, enabling construction of a virus with receptor-specific
      infectivity. Retargeting of adenovirus based vectors using the same polymer
      peptide construct enhanced levels of transgene expression in HUVECs to greater
      than 15 times that observed using parental (unmodified) virus, whilst restoring
      levels of transgene expression in non-endothelial cell lines tested. The use of
      constructs based on conjugates between hydrophilic polymers and small receptor
      binding oligopeptides as agents for retargeting viral or non-viral vectors to
      cellular receptors represents a simple alternative to the use of antibodies as
      targeting ligands for cell specific gene delivery.

PMID- 15848954
TI  - In vivo evidence for the efflux transport of pentazocine from the brain across
      the blood-brain barrier using the brain efflux index method.
AB  - The efflux transport of pentazocine (PTZ) from the brain across the blood-brain
      barrier (BBB) was investigated using the Brain Efflux Index method. PTZ was
      eliminated with the apparent elimination half-life of 13.0 min after
      microinjection into the parietal cortex area 2 region of the rat brain. The
      apparent efflux clearance of PTZ across the BBB was 137 microl/min/g brain, which
      was calculated from the elimination rate constant (5.35 x 10(-2) min(-1) and the
      distribution volume in the brain (2.56 ml/g brain). The efflux transport of PTZ
      was decreased in the presence of unlabeled PTZ, suggesting that PTZ is eliminated
      by a carrier-mediated transport system across the BBB. To characterize the efflux
      transport of PTZ from the brain in vivo, the effects of several compounds on the
      efflux transport of PTZ were investigated. P-glycoprotein (P-gp) inhibitors
      (verapamil and quinidine) reduced the PTZ efflux transport. In addition, the
      efflux transport of PTZ was inhibited by organic cations such as l-carnitine and
      tetraethylammonium (TEA), whereas organic anions such as p-aminohippuric acid,
      probenecid and taurocholate did not affect the PTZ efflux transport. The present
      results suggest that PTZ is transported from the brain across the BBB via l
      carnitine/TEA-sensitive carrier-mediated efflux transport system(s) in addition
      to P-gp.

PMID- 15848955
TI  - Structural rearrangements in RNA on the binding of an antisense oligonucleotide:
      implications for the study of intra-molecular RNA interactions and the design of
      cooperatively acting antisense reagents with enhanced efficacy.
AB  - We show that binding of an antisense oligonucleotide can lead to considerable
      changes in the target mRNA structure. The approaches described here are not only
      useful in the study of intra-molecular interactions in RNAs but can also be used
      to design oligonucleotides that facilitate binding of other antisense reagents.
      Such "cooperatively acting" antisense reagents have the potential to overcome
      several problems faced in their use, for example, low efficacy and non
      specificity. To provide proof-of-principle, radiolabelled cyclin B5 transcript, a
      model mRNA, was hybridised with an antisense oligonucleotide array. An
      oligonucleotide sequence was selected from the array hybridisation data and was
      used in an RNase H/oligonucleotide library (dN12) assay to assess its ability to
      enhance cleavage of target RNA. This oligonucleotide ("facilitator") greatly
      enhanced cleavage of B5 RNA at a neighbouring site. The precise position and
      sequence of this "new" site was determined by further hybridisation of RNA
      facilitator mixture to the B5 antisense array. Antisense oligonucleotides
      designed from the new region were used in combination with the facilitator in a
      cell-free system. The presence of the facilitator considerably enhanced cleavage
      of B5 RNA with these oligonucleotides. These approaches may be useful in
      designing antisense reagents against sequences of specific interest, such as,
      gene fusion sites, splice variants, mutant alleles and tightly structured RNA
      sites.

PMID- 15848957
TI  - Polymeric micelles for delivery of poorly soluble drugs: preparation and
      anticancer activity in vitro of paclitaxel incorporated into mixed micelles based
      on poly(ethylene glycol)-lipid conjugate and positively charged lipids.
AB  - Paclitaxel-loaded mixed polymeric micelles consisting of poly(ethylene glycol)
      distearoyl phosphoethanolamine conjugates (PEG-PE), solid triglycerides (ST), and
      cationic Lipofectin lipids (LL) have been prepared. Micelles with the optimized
      composition (PEG-PE/ST/LL/paclitaxel = 12/12/2/1 by weight) had an average
      micelle size of about 100 nm, and zeta-potential of about -6 mV. Micelles were
      stable and did not release paclitaxel when stored at 4 degree C in the darkness
      (just 2.9% of paclitaxel have been lost after 4 months with the particle size
      remaining unchanged). The release of paclitaxel from such micelles at room
      temperature was also insignificant. However, at 37 degree C, approx. 16% of
      paclitaxel was released from PEG-PE/ST/LL/paclitaxel micelles in 72 h, probably,
      because of phase transition in the ST-containing micelle core. In vitro
      anticancer effects of PEG-PE/ST/LL/paclitaxel and control micelles were evaluated
      using human mammary adenocarcinoma (BT-20) and human ovarian carcinoma (A2780)
      cell lines. Paclitaxel in PEG-PE/ST/LL micelles demonstrated the maximum anti
      cancer activity. Cellular uptake of fluorescently-labeled paclitaxel-containing
      micelles by BT-20 cells was investigated using a fluorescence microscopy. It
      seems that PEG-PE/ST/LL micelles, unlike micelles without the LL component, could
      escape from endosomes and enter the cytoplasm of BT-20 cancer cells thus
      increasing the anticancer efficiency of the micellar paclitaxel.

PMID- 15848958
TI  - Graft repair of a peripheral nerve without the sacrifice of a healthy donor nerve
      by the use of acutely dissociated autologous Schwann cells.
AB  - We hypothesised that pieces of nerve that are normally trimmed away during graft
      repair could be a source of Schwann cells and used to create an autologous cell
      containing nerve graft. To test the idea a transsection injury was made on the
      rat sciatic nerve. Seven days later, pieces from the proximal and distal stumps
      were used for immediate isolation of its non-neuronal cells. These cells, of
      which 80% were Schwann cells, were injected into a silicone tube bridging a 10 mm
      gap on the same nerve. Tubes containing cells showed superior regeneration of
      nerve fibres across the gap compared with tubes with no cells. This new repair
      technique is rapid, does not require the sacrifice of a healthy donor nerve, or
      the time-consuming culturing and expansion of Schwann cells. The method has the
      potential to replace current methods for repair of extended nerve injuries.

PMID- 15848959
TI  - Effects of clopidogrel and high dose aspirin on survival of skin flaps in rats.
AB  - Clopidogrel is a new antiplatelet agent with a different mechanism of action from
      aspirin. It is thienopyridine derivative that is chemically related to
      ticlopidine, which irreversibly inhibits platelet aggregation by selectively
      binding to adenylate-cyclase-coupled adenosine diphosphate receptors on the
      platelet's surface. Aspirin is an antiplatelet agent that acetylates cyclo
      oxygenase and decreases the products of arachidonic acid metabolism, including
      thromboxane and prostacyclin. Necrosis of a flap is still an important
      complication in reconstructive surgery. To investigate the effects of clopidogrel
      or high dose aspirin on the survival of skin flaps, 30 rats were divided into
      three groups of 10 animals each: a control group, a clopidogrel group, and a high
      dose aspirin group. No pharmacological agents were used in the control group. Of
      the two treated groups, the first was given clopidogrel 50 mg/kg/day and the
      second aspirin 200 mg/kg/day for three days before the operation. After seven
      days the viable areas of each flap were evaluated and the mean (SD) percentage in
      the control group was 47 (6), in the clopidogrel group 63 (4), and in the aspirin
      group 65 (5). Although the mean area of flaps that survived in the aspirin group
      was slightly higher than in the clopidogrel group, the difference was not
      significant (p = 0.54).

PMID- 15848960
TI  - Computed tomography of alveolar bone grafts 20 years after repair of unilateral
      cleft lip and palate.
AB  - The aim of this study was to estimate the clinical condition and amount of
      remaining grafted bone 20 years after final repair of unilateral cleft lip and
      palate. Eighteen consecutive patients had computed tomograms (CT) and clinical
      examination 20 years or more after secondary bone grafting which had been done at
      ages of 7-11 years. The images were obtained with a spiral CT with 1 mm
      collimation, and reconstructed as three-dimensional volumes with reformatted cut
      planes. The area of grafted bone was measured in a plane perpendicular to the
      curved axis of the alveolar arch and compared with the area corresponding section
      through the non-cleft side. The clinical examination showed satisfactory results
      in all. CT indicated a mean cross sectional area of 97 mm2 on the cleft side
      compared with 157 mm2 on the non-cleft side. The bone mass was significantly less
      on the grafted cleft side (p < 0.001), but the functional results were
      satisfactory.

PMID- 15848961
TI  - Comparison of intraoral radiography and computed tomography in evaluation of
      formation of bone after grafting for repair of residual alveolar defects in
      patients with cleft lip and palate.
AB  - For one year we studied postoperative computed tomograms (CT) and intraoral
      radiographs for 29 patients with unilateral alveolar clefts. Interdental bone
      height and the bony boundary on the nasal side were assessed on intraoral films
      and compared with the evaluation by CT. Twenty-four cases had adequate
      interdental bone height as assessed by intraoral films. However, 10 of these 24
      cases showed insufficient anteroposterior depth on CT. Two of the remaining five
      cases were also overestimated by the intraoral radiograph. All cases had
      sufficient bony boundary on the nasal side on intraoral radiography. However, CT
      showed that bone formation on the nasal side off two cases was significantly
      worse than that on the non-cleft side. Consequently, about 40% of surgical
      outcomes may be overestimated by intraoral radiographs. CT therefore seems to
      give a better assessment of the clinical outcome than intraoral radiographs and
      should be considered as an adjunct in difficult clinical cases.

PMID- 15848962
TI  - Three-year evaluation of late breast reconstruction with a free transverse rectus
      abdominis musculocutaneous flap in a county hospital in Sweden: a retrospective
      study.
AB  - We present our three-year experience of late breast reconstruction with
      conventional free TRAM flaps in 16 consecutive patients in a Swedish county
      hospital. The breast reconstruction was done unilaterally in 14 and bilaterally
      in two, giving a total of 18 free TRAM flaps in 16 patients. Six patients
      developed anastomotic or systemic thromboembolic events during or after the
      operation' three developed during the operation, and one required reoperation for
      postoperative thrombosis. No flaps were lost. Three patients developed deep
      venous thrombosis (DVT) or pulmonary embolism (PE) postoperatively; the two
      patients with DVT were later found to be resistant to activated protein C. The
      patient with a PE had developed multiple metastases by one year postoperatively.
      We compared the six patients who developed anastomotic and systemic
      thromboembolic events with those whose operations were uncomplicated and no
      significant differences were found either in their characteristics or overall
      events during operation.

PMID- 15848963
TI  - Blepharoplasty with aponeurotic fixation corrects asymmetry of the eyebrows
      caused by paralysis of the unilateral frontalis muscle in Orientals.
AB  - Paralysis of the frontalis muscle causes ipsilateral brow ptosis and
      contralateral hypermotility of the non-paralytic frontalis muscle in Oriental
      patients. In this paper, we describe an effective way of correcting such
      asymmetry by using blepharoplasty with aponeurotic fixation, and three case
      reports were presented. This procedure makes it possible to reduce the
      hypermotility of the non-paralytic frontalis muscle, and symmetry of the brows
      can be achieved easily with minimal brow lift. All three patients had symmetrical
      brows six months postoperatively. Although we think that brow ptosis may recur
      eventually, if symmetry is obtained as a result of minimal brow lift, we think
      that our method can delay recurrence.

PMID- 15848964
TI  - Total reconstruction of the upper lip after resection of a malignant melanoma.
AB  - The upper lip was totally reconstructed with a radial forearm sensory flap and
      vermilionplasty using medical tattooing after resection of a malignant melanoma.
      Three courses of chemotherapy (dacarbazine, nimustine, and vincristine) were
      given postoperatively. The reconstructed lip had good contour, colour, and
      sensory recovery.

PMID- 15848965
TI  - Merkel cell carcinoma in the orbitopalpebral region.
AB  - Trabecular carcinoma is a rare cutaneous neuroendocrine carcinoma that probably
      originates from the Merkel cells that are usually found in the basal layer of the
      epidermis. The treatment of Merkel cell carcinoma is controversial and there is
      no specific therapeutic protocol because of the small number of cases that have
      been published. The procedures used to treat Merkel cell carcinoma must be
      tailored to minimise morbidity while maximising survival. Because the condition
      is so rare and difficult to diagnose and treat, we report three cases of
      orbitopalpebral tumours that confirm the local and regional aggressiveness and
      the high metastatic potential of this tumour.

PMID- 15848966
TI  - Successful management of a small infant born with a large meningomyelocele using
      a temporary artificial dermis.
AB  - A boy with a large meningomyelocele was born at 29 weeks' gestation. An
      artificial dermis was applied to the meningomyelocele six hours after birth. Four
      months later he had grown well, and the meningocele was reconstructed with a
      bilateral latissimus dorsi musculocutaneous flap.

PMID- 15848967
TI  - Dermoid cyst at the suprasternal notch: an adult case.
AB  - We present a case of a 39-year-old Japanese man with a two-year history of a mass
      in his suprasternal notch. Histopathologically the diagnosis was confirmed as a
      dermoid cyst; the cyst wall was almost normal with an epidermal structure
      consisting of sebaceous and apocrine glands and on the inside there were keratin
      materials and hair shafts. A dermoid cyst at the suprasternal notch is rare, and
      in an adult is the first as far as we know.

PMID- 15848968
TI  - Treatment of Kienbock disease in an 11-year-old girl with temporary fixation of
      the scaphotrapeziotrapezoidal joint.
AB  - An 11-year-old girl with Kienbock disease (stage IIIA) was treated by temporary
      scaphotrapeziotrapezoidal fixation. It was fixed in a cast for four weeks and
      wires removed after eight weeks. Follow up examinations showed that movement of
      the wrist and grip strength were improved, and she had no pain while
      revascularisation of the lunate could be seen on magnetic resonance imaging.

PMID- 15848970
TI  - Monitoring human exposures to upper-room germicidal ultraviolet irradiation.
AB  - After decades of neglect, the resurgence of tuberculosis in the United States
      between 1985 and 1992 renewed interest in the use of upper room ultraviolet
      germicidal irradiation to interrupt the transmission of airborne infections. More
      recently the bioterrorism threat and the appearance of new pathogens with the
      potential for airborne spread, such as severe acute respiratory syndrome (SARS),
      have stimulated installations of upper-room irradiation systems. The objective is
      to flood the entire volume of a room above 6.5 ft with high intensity ultraviolet
      germicidal irradiation, while minimizing unintentional irradiance below 6.5 ft to
      avoid eye and skin irritation. Air exchanges between the upper and lower room
      result in air disinfection of the occupied space. Designers of these systems have
      adopted the practice of limiting the maximum lower room irradiance at every point
      to less than the continuous 8-hour time-weighted average threshold limit value,
      severely limiting the irradiation intensity in the upper room and thereby
      reducing one of the two major factors determining germicidal effectiveness, the
      other being room air mixing. The hypothesis of this study is that eye and skin
      exposure will be well below the recommended safe dose even when maximum eye-level
      irradiance levels in the room exceed the 8-hour continuous exposure threshold
      limit. The method employed was to have subjects wear a small photometer that
      recorded total ultraviolet dose over the period of exposure while subjects went
      about their normal routine, and comparing this value with a hypothetical dose
      calculated from the highest measured eye-level irradiance. The results of the
      study, based on a limited number of observations, confirmed the hypothesis.
      Observed doses were one-third to a factor of a hundred or more lower than the
      doses calculated from maximum eye-level irradiances measurements in the
      occupants' spaces.

PMID- 15848971
TI  - Chronic myofascial pain, disk displacement with reduction and psychosocial
      factors in Finnish non-patients.
AB  - This study aimed to determine chronic groups of myofascial pain and chronic disk
      displacement with reduction over a 1-year period, and to study the relationship
      between psychological status and these chronic subgroups of temporomandibular
      disorders (TMD) in non-patients. A total of 211 subjects (males 47%, mean age 46
      years; standard deviation 6) attended examinations in 1999 and 2000 performed
      according to the Research Diagnostic Criteria for Temporomandibular Disorders
      (RDC/TMD). Chronic myofascial pain was found in 7% and chronic disk displacement
      with reduction in 11% of subjects; new diagnoses were made in only 4% and 1% of
      the subjects, respectively. An increase in the level of somatization by 1 step
      increased the probability of having chronic myofascial pain by over 3 times (P =
      0.006). Myofascial pain and disk displacement with reduction seem to be
      relatively common and fluctuating in nature in non-patients. As somatization
      associated significantly with myofascial pain, this should be borne in mind in
      the management of TMD. The results strengthen the rationale of the
      biopsychosocial orientation in health care.

PMID- 15848972
TI  - Association of photoactivation methods and low modulus liners on marginal
      adaptation of composite restorations.
AB  - The aim of this study was to evaluate the effect of photoactivation methods,
      resin liners, and the association of these techniques on the marginal adaptation
      of composite restorations. One-hundred-and-twenty bovine incisors were selected.
      A circular cavity was prepared in a flat dentin area on the buccal surface and
      the Scotchbond Multi Purpose system was applied. These teeth were assigned to
      four groups in accordance with lining technique: control (one adhesive layer),
      three adhesive layers individually photoactivated, Filtek Flow, and Protect Liner
      F. Each group was subdivided depending on the photoactivation method: continuous
      light, soft-start, or intermittent light. All cavities were restored with Filtek
      Z250 and then polished. Caries detector was applied on each specimen for 5 s in
      order to verify marginal adaptation through dye-staining of the gaps formed on
      the outer margins. Images of the stained gaps were observed under the
      stereomicroscope, and transferred to a computer measurement program in order to
      determine gap length. Data were submitted to ANOVA and Tukey's test (P < 0.05).
      Significant differences among the lining techniques were only observed using the
      photoactivation method with continuous light. In this case, the lining technique
      with Filtek Flow significantly increased marginal adaptation of the composite to
      the outer dentin margins compared with the results of the control group. The
      other lining techniques showed intermediate values and no statistical difference
      from the other groups. For the photoactivation methods, intermittent light showed
      the best marginal quality of all the methods. This was statistically significant
      only for the control lining technique.

PMID- 15848973
TI  - Effect of electrical tooth stimulation on blood flow and immunocompetent cells in
      rat dental pulp after sympathectomy.
AB  - Previous experiments show that nerves have effect on the emigration of
      immunocompetent cells during acute neurogenic inflammation. The present study
      aims to determine whether the sympathetic or sensory nerves are responsible for
      emigration of CD43+ and I-A antigen-expressing cells in the dental pulp after
      electrical tooth stimulation. Wistar rats were used. Experimental rats (n = 6)
      had the right superior cervical ganglion removed (SCGx), whereas control rats (n
      = 6) had sham surgery. Fourteen days later, electrical stimulation of the right
      maxillary 1st molar was performed in both groups for 20-25 s every 5th min for a
      total period of 4 h. Changes in pulpal blood flow (PBF) were recorded with a
      laser Doppler flowmeter. All rats were transcardiacally perfused and processed
      for immunohistochemistry using antibodies against neuropeptides and immune cells.
      Intermittent electrical stimulation consistently increased PBF and depleted
      sympathetic and sensory neuropeptides in the dental pulp. The increase in PBF
      gradually decreased and approached control values at the end of the 4 h
      stimulation period. A significant increase in the number of I-A antigen
      expressing dendritic cells was found in both the SCGx (P < 0.001) and control
      rats (P < 0.007). In contrast, tooth stimulation did not increase the number of
      CD43+ cells in the SCGx rats compared to the unstimulated contralateral control
      molar. Significantly more CD43+ PMN cells (P < 0.01) were found in the control
      rats after stimulation. It is concluded that stimulation of sympathetic nerves
      causes recruitment of CD43+ PMN cells, whereas stimulation of sensory nerves
      causes emigration of I-A antigen-expressing dendritic cells in the dental pulp.

PMID- 15848974
TI  - In vitro quantification of white spot enamel lesions adjacent to fixed
      orthodontic appliances using quantitative light-induced fluorescence and
      DIAGNOdent.
AB  - The aims of this in vitro study were 2-fold: 1) to evaluate two fluorescence
      methods (DIAGNOdent and QLF (quantitative light-induced fluorescence)) for
      quantification of white spot lesions adjacent to fixed orthodontic appliances;
      and 2) to determine the inter-observer agreement of the DIAGNOdent and QLF
      methods for quantification of incipient enamel lesions adjacent to fixed
      orthodontic appliances. Forty-one premolar teeth with visually sound smooth
      surfaces or visually white spot enamel lesions were included in the study.
      Orthodontic brackets were fixed adjacent to the lesions, thus simulating the
      position of fixed appliances during orthodontic treatment. All teeth were
      measured using both the DIAGNOdent and QLF methods. Of the 41 teeth, 20 smooth
      surfaces were randomly selected and analyzed by 4 operators using both DIAGNOdent
      and QLF. The teeth were sectioned into 300-microm-thick slices using a water
      cooled diamond saw and the slices manually ground to 80-100 microm thickness.
      Histopathology and transverse microradiography were performed to provide the gold
      standards for verification of lesion depth and mineral loss, respectively. The
      Spearman rank correlation coefficients between lesion depth determined by
      histopathology and the DIAGNOdent and QLF were 0.76 and 0.82, respectively,
      whereas the Pearson correlation coefficients between mineral loss and the two
      methods were 0.64 and 0.84, respectively. Inter-observer agreement was found to
      be 0.80 and 0.93 for DIAGNOdent and QLF, respectively. In conclusion, QLF may be
      a suitable method for quantifying incipient carious lesions adjacent to fixed
      orthodontic appliances.

PMID- 15848975
TI  - Dental health professionals' treatment of children with disabilities: a
      qualitative study.
AB  - As children and adolescents with disabilities may be difficult to treat, there is
      a risk that the disability may constitute a barrier preventing these children
      from receiving good odontological treatment in the same conditions as other
      children. OBJECTIVES: To describe Swedish dental care professionals'
      understanding and knowledge of orofacial problems and treatment needs in children
      with disabilities. METHODS: In-depth interviews focusing on orofacial function,
      and carried out with 18 informants (dentists, dental hygienists, dental
      assistants), were transcribed verbatim and analysed in open and focused
      (selective) coding processes in accordance with grounded theory. RESULTS: A core
      category labelled variability in treatment with the dimensions professional
      uncertainty and professional commitment emerged from the data in the analysis.
      Variability in treatment could be described as forming a continuum between two
      end-points captured in the dimensions. The dental teams' treatment of children
      with disabilities and their families could be placed anywhere along this
      continuum depending on contributing individual strategies and/or organizational
      conditions. CONCLUSIONS: The dental treatment for children with disabilities
      varied greatly, implying a risk for inequalities in treatment as well as in oral
      health. There is a need for more educational opportunities, better financing, and
      more support on the organizational level in order to improve odontological care
      for young special care patients.

PMID- 15848976
TI  - Can school-based oral health education and a sugar-free chewing gum program
      improve oral health? Results from a two-year study in PR China.
AB  - The purpose of the study was to assess the outcome of school-based oral health
      education (OHE) and a sugar-free chewing gum program on the oral health status of
      children in terms of reduced caries increment and gingival bleeding over a period
      of 2 years. Nine primary schools randomly chosen from one district were divided
      into three groups: OHE group (Group E), sugar-free chewing gum in addition to OHE
      group (Group G), and the control group (Group C). All children of grade 1 (aged 6
      7 years) were recruited (n = 1342). After 2 years, 1143 children remained in the
      study group at follow-up. The overall drop-out rate was about 15%. Data on dental
      caries and gingival bleeding were collected by clinical examination. The results
      showed that the mean increment of DMFS in Group G was 42% lower than in groups E
      and C (P < 0.05). The mean increments in F-S were higher in Groups G and E than
      in Group C (P < 0.01). The gingival bleeding scores were statistically
      significant among the three groups. Compared to Group C, the mean increment in
      bleeding scores of Group G was 71% lower (P < 0.01) and in Group E 42% lower (P <
      0.05). The school-based OHE programs had some positive effect improving
      children's oral hygiene; in certain circumstances children may benefit from using
      polyol-containing chewing gum in terms of reduced dental caries.

PMID- 15848977
TI  - Periodontal disease in a group of Swedish adult snuff and cigarette users.
AB  - The aim of this study was to compare the prevalence of periodontal disease in
      different groups of tobacco users. Participants (n = 1674) were selected from an
      initial random sample of residents in the Stockholm region. Socio-demographic
      characteristics and life-time history of tobacco use were registered in a self
      completed questionnaire, followed by a clinical examination. Cumulative life-time
      tobacco use was analyzed in pack-years and can-years as the exposure of interest.
      Among participants, 50.8% were females and 49.2% were males. Life-time tobacco
      use was categorized into four mutually exclusive categories. Approximately, two
      thirds of snuff users had combined snuff use with cigarette smoking during their
      life. Tobacco users had a higher prevalence of periodontal disease compared to
      never users. Exclusive smokers and mixed users presented the less favorable
      situation. Unhealthy periodontal conditions increased with increasing exposure to
      smoking, most evidently at the level of 15 or more pack-years. There was a
      significant positive association between current or former smoking and
      periodontal disease (OR = 2.7, CI = 1.7-4.3 and OR = 2.0, CI = 1.2-3.3,
      respectively) even after adjustment for plaque level. An indication of
      association was also apparent with former snuff use. Plaque was independently
      associated with periodontal disease, with a dose gradient. Smoking is associated
      with periodontal disease independently of plaque. Combining cigarette smoking and
      snuff use during life does not convey a decreased probability of being diagnosed
      with periodontal disease compared to smoking exclusively.

PMID- 15848978
TI  - Effect of topical applications of a chlorhexidine/thymol-containing varnish on
      fissure caries assessed by laser fluorescence.
AB  - The aim of this study was to monitor the effect of an antibacterial varnish using
      the readings of a caries-detecting device (DIAGNOdent) in fissures of young
      permanent molars. The material consisted of 32 healthy patients with a mean age
      of 14.1 years undergoing orthodontic treatment with fixed appliances. The
      inclusion criteria were presence of one homologous pair of 2nd upper or lower
      molars with clinically intact occlusal surfaces. A split-mouth study design was
      used in which the fissures were treated with either an antibacterial
      chlorhexidine/thymol-containing varnish or a placebo varnish every 6th week. The
      follow-up period was 42 weeks and laser fluorescence (LF) readings were carried
      out every 12th week. The mean LF values increased significantly (P < 0.05) after
      24, 36, and 48 weeks compared to baseline following the placebo treatments but
      not after treatment with the active antibacterial varnish. During the study
      period, micro-cavities were diagnosed in two test-treated and five placebo
      treated teeth. In conclusion, the results reinforce previous findings that
      frequent applications of a chlorhexidine/thymol-containing dental varnish might
      have a protective role in fissures of young permanent molars and that this could
      be monitored with a chair-side caries detecting LF device.

PMID- 15848979
TI  - Treatment outcome of appliance therapy in temporomandibular disorder patients
      with myofascial pain after 6 and 12 months.
AB  - AIM: To compare the long-term effect of treatment with a stabilization appliance
      (group T) and treatment with a control appliance (group C) in temporomandibular
      disorder (TMD) patients with myofascial pain. METHODS: In this controlled trial,
      60 patients (mean age 29 years) with myofascial pain were evaluated after 10
      weeks of treatment with either a stabilization appliance or a control appliance.
      All 60 patients were then assigned to 1 of 3 groups according to demand for
      treatment. Seventeen patients from group C requested another appliance and were
      given a stabilization appliance, thus creating a mixed group (group M). RESULTS:
      A significant difference in improvement of overall subjective symptoms in an
      intent-to-treat analysis between groups T and C was found at the follow-ups. In a
      survival analysis of treatment compliance, a significant difference was found
      between groups T and C. At the 6- and 12-month follow-ups, a significant
      reduction in myofascial pain, as measured on a visual analog scale, was found in
      all three groups. A significant decrease in frequency and intensity of myofascial
      pain was found in group T at the follow-ups. A significant decrease in number of
      tender sites on the masticatory muscles was found in group T at the follow-ups.
      CONCLUSION: The results support the conclusion that the positive treatment
      outcome obtained by use of a stabilization appliance to alleviate the signs and
      symptoms in patients with myofascial pain persisted after 6 and 12 months. Most
      patients in groups T and M reported positive changes in overall subjective
      symptoms in this trial. We therefore recommend use of the stabilization appliance
      in the treatment of TMD patients with myofascial pain.

PMID- 15848980
TI  - Clinical evaluation of the plaque-removing ability of three different
      toothbrushes in a mentally disabled group.
AB  - The aim of the study was to evaluate the efficacy of plaque removal of three
      different toothbrushes on mentally disabled children in two different age groups.
      A manual triple-headed brush (SuperBrush; Dento Co. AS [junior, regular])
      compared with a new manual toothbrush (CrossAction; Oral-B [35 compact, 40
      regular]) and an electric toothbrush with an oscillating rotating head (Braun
      Plaque Control 3D [Braun 3D]; Oral-B [D15525]). Fifteen children aged 6-12 (Group
      A) and 15 children aged 13-18 (Group B) with mild mental disabilities
      participated in the single-blind clinical study. To obtain a plaque-free
      condition at baseline, professional tooth-cleaning was performed on each
      participant. After instructions on how to use the toothbrushes, each group
      started the experiment. After 1 week of application, the Quikley Hein (QH) plaque
      index and the approximal plaque index (API) were used to assess the oral hygiene
      status of each participant. This was followed by a week of recess before each
      group switched to the next type of toothbrush. The study lasted for 5 weeks.
      Compared to the two other brushes, the Braun 3D was more effective in removing
      plaque (means of QHI: 1.54 (Braun 3D), 1.77 (SuperBrush), and 2.15 (CrossAction)
      in total; means of API 1.37 (Braun 3D), 1.52 (SuperBrush), 1.94 (CrossAction).
      The study indicated that the electric toothbrush is the most effective for
      removing dental plaque in mentally disabled children, whereas the SuperBrush is a
      good alternative.

PMID- 15848982
TI  - HLA-Cw*0602 associates more strongly to psoriasis in the Swedish population than
      variants of the novel 6p21.3 gene PSORS1C3.
AB  - The PSORS1 locus in the major histocompatibility complex region on chromosome
      6p21.3 contains a major predisposing factor for psoriasis for which several
      candidate genes have been tested. The analyses are complicated by strong linkage
      disequilibrium in the region and the complex genetic background of psoriasis. In
      the search for an alternative to HLA-C we have identified a novel gene, PSORS1C3,
      and characterized it with regard to psoriasis. PSORS1C3 is located approximately
      7 kb centromeric to POU5F1. A putative protein of 58 amino acids was predicted
      and expression was detected in both normal and psoriasis skin. Sequencing of the
      coding region revealed a total of 11 single nucleotide polymorphisms. When
      comparing the frequencies of PSORS1C3 variants in a case-control material in the
      Swedish population, three single nucleotide polymorphisms displayed significant
      association with psoriasis. This association appeared to be HLA-Cw*0602-dependent
      due to linkage disequilibrium, thus HLA-C remains the strongest associating
      factor in the region.

PMID- 15848983
TI  - Effects of pretreatment with a urea-containing emollient on nickel allergic skin
      reactions.
AB  - The aim of this study was to evaluate the effect of a moisturizer containing urea
      on allergic contact dermatitis. Twenty-five nickel-sensitized patients and five
      controls (non-sensitized volunteers) applied such a moisturizer on the volar side
      of one forearm twice daily for 20 days, while the other forearm served as the
      control. After treatment with the moisturizer, patch tests with 0%, 0.5% and 2%
      NiSO4 in petrolatum were applied in a randomized manner on each arm. After 72 h,
      the skin reactions were blindly evaluated by clinical scoring and by measuring
      transepidermal water loss and electrical impedance. After treatment, the baseline
      transepidermal water loss values were lower and the baseline magnitude impedance
      index values were higher on the pretreated forearm. According to clinical scoring
      and measurements with the two physical measurement techniques, the degree of the
      patch test reactions was equal. All control subjects had negative nickel tests.
      We concluded that the skin reactivity to nickel in nickel-sensitized patients is
      not significantly affected by use of the urea-containing moisturizer.

PMID- 15848984
TI  - Evaluation of phototoxic properties of antimicrobials used in topical
      preparations by a photohaemolysis test.
AB  - Antimicrobials are widely used in topical formulations as preservatives or as
      therapeutically active agents. Photosensitization by such compounds has not yet
      been studied systematically. To identify possible phototoxic properties,
      antimicrobials (benzyl alcohol, bronopol, chloracetamide, clioquinol,
      diazolidinyl urea, ethylenediamine dihydrochloride, formaldehyde, glutaraldehyde,
      imidazolidinyl urea, sodium benzoate, propylene glycol) were evaluated in vitro
      by means of a photohaemolysis test using suspensions of human erythrocytes.
      Irradiations were performed with UVA- and UVB-rich light sources. In the presence
      of bronopol or clioquinol, there was photohaemolysis up to 78.1% or 48.5% with
      UVA and up to 100% or 34.3% with UVB, respectively. The phototoxic effect
      depended on the concentration of the compounds and the UV doses administered.
      None of the other substances tested caused significant photohaemolysis. It is
      concluded that bronopol and clioquinol exert phototoxic effects in vitro and thus
      might also cause photosensitization when used on the skin. The clinical
      significance of this has to be established by further work.

PMID- 15848985
TI  - The prevalence of Malassezia yeasts in patients with atopic dermatitis,
      seborrhoeic dermatitis and healthy controls.
AB  - Cultures for Malassezia yeasts were taken from both normal-looking skin and
      lesional skin in 124 patients with atopic dermatitis, 16 patients with
      seborrhoeic dermatitis and from normal skin of 31 healthy controls. Positive
      Malassezia growth was found in fewer patients with atopic dermatitis (56%) than
      in patients with seborrhoeic dermatitis (88%) or in healthy controls (84%,
      p<0.01). In the patients with atopic dermatitis, fewer positive cultures were
      found in lesional (28%) than in non-lesional skin (44%, p<0.05), while positive
      cultures were found in 75% of both lesional and non-lesional skin of patients
      with seborrhoeic dermatitis (not significant). M. sympodialis dominated in
      patients with atopic dermatitis (46%) and in healthy controls (69%). In patients
      with seborrhoeic dermatitis both M. sympodialis and M. obtusa were cultured in
      43%. A Malassezia species extract mixture would increase the possibility of
      detecting IgE sensitization to Malassezia in patients with atopic dermatitis.

PMID- 15848986
TI  - UVB 311 nm tolerance of vitiligo skin increases with skin photo type.
AB  - It is assumed that skin is protected against sunburn by melanin. In patients with
      vitiligo, there are white patches in the normal pigmented skin. We noticed that
      there is a difference in burning capacity of these white patches between people
      with different skin types. With UVB 311 nm lamps, we irradiated both lesional and
      non-lesional skin with increasing doses in 33 patients with vitiligo, divided
      into 5 groups according to skin type (II-VI). Twenty-four hours later we assessed
      the minimal erythema dose and found a correlation between skin type and UV
      sensitivity in both lesional skin and normal skin. We suggest that there must be
      a protection mechanism, other than that offered by melanin pigmentation. The
      antioxidant status may play a role in this phenomenon.

PMID- 15848987
TI  - Significance of the stigmatization experience of psoriasis patients: a 1-year
      follow-up of the illness and its psychosocial consequences in men and women.
AB  - Feelings of stigmatization are an important somatopsychic consequence of
      psoriasis, affecting the quality of life. It is thus relevant to supplement
      reliable statements about the detailed changes of stigmatization experience and
      psoriasis over time. In this study we compared the Psoriasis Area and Severity
      Index (PASI), the 'self-administered PASI' (SPASI) and the 'Questionnaire on
      Experience with Skin Complaints' of 166 psoriasis patients (64 women, 102 men) in
      a 1-year follow-up to assess the relation between these factors over time. The
      results suggest a more pronounced feeling of discrimination in women with no
      significant somatic differences between gender at the first measurement. In a
      prospective evaluation we found a clear proportion of 'discordant' courses of
      these parameters, mainly in women, indicating a contradictory relation of somatic
      improvement or deterioration vs subjective experience with skin complaints. All
      in all, these results show a moderate but significant relevance of skin state for
      feeling of stigmatization over time only in men, thus suggesting a considerable
      influence of other psychic variables, probably coping skills, especially in
      women.

PMID- 15848988
TI  - The prevalence of fibromyalgia among patients with psoriasis.
AB  - The aim of the present study was to investigate the prevalence of fibromyalgia
      and allied symptoms in patients with psoriasis. During a 3-year period from 1997
      until 2000, 1269 patients were consecutively diagnosed with psoriasis. All
      patients were questioned about musculoskeletal symptoms and those with such
      symptoms were further examined according to a standardized protocol. In total 335
      of 1269 patients had musculoskeletal symptoms. More women than men had such
      complaints, 33% versus 18.5%, respectively. As many as 13% of the women fulfilled
      the American College of Rheumatology 1990 (ACR-90) criteria for fibromyalgia,
      while 14.1% had symptoms compatible with chronic widespread pain without meeting
      the fibromyalgia criteria. In total, 8.3% suffered from fibromyalgia and 9% from
      chronic widespread pain. The results indicate that fibromyalgia and allied
      symptoms are frequent in female patients with psoriasis and constitute important
      problems with regard to disability and health-related quality of life. Only 35 of
      105 patients with fibromyalgia had previously been diagnosed with psoriasis and
      the diagnostic label of fibromyalgia was new to 51 of them. Female patients with
      symptoms of psoriasis and pain seem to constitute a subgroup which deserves
      further studies.

PMID- 15848989
TI  - Does long-lasting hand dermatosis have an influence on everyday living among
      teenagers?
AB  - The purpose of this longitudinal study was to examine a cohort of secondary
      school pupils, aged 16-19 years (47 females and 18 males) with a 1-year
      prevalence of hand dermatosis. The study deals with the pupils' history of atopy,
      self-reported symptoms, exacerbating factors, protection habits, choice of
      education programme, self-rated health and impact on everyday life. The results
      showed that 61.5% of the pupils had a history of atopic dermatitis; 78% did not
      use protective gloves. Females reported use of corticosteroids more often than
      males. In all, 60% had not been given information at school about future
      occupational risks, when choosing education. The cohort changed education
      programme significantly more often than pupils reporting not having hand
      dermatosis. However, the cohort estimated their health as being as good as that
      of adolescents in the general population. The neglect of risks in choosing a
      future profession may cause not only suffering for the individual, but also costs
      for society.

PMID- 15848990
TI  - A double-blind treatment study of bacterial vaginosis with normal vaginal
      lactobacilli after an open treatment with vaginal clindamycin ovules.
AB  - The expected 4-week cure rate after conventional treatment of bacterial vaginosis
      are only 65-70%. In an attempt to improve the cure rate by adding probiotic
      lactobacilli we performed a double-blind placebo-controlled study of adjuvant
      lactobacilli treatment after an open treatment with vaginal clindamycin ovules.
      Women with bacterial vaginosis as defined by Amsel's criteria were treated with
      clindamycin ovules. Vaginal smears were collected and analysed according to
      Nugent's criteria. During the following menstruation period the women used, as an
      adjuvant treatment, either lactobacilli-prepared tampons or placebo tampons. The
      lactobacilli tampons were loaded with a mixture of freeze-dried L. fermentum, L.
      casei var. rhamnosus and L. gasseri. The cure rate was recorded after the second
      menstruation period. There was no improvement in the cure rate after treatment
      with lactobacilli-containing tampons compared to placebo tampons; the cure rates
      as defined by Amsel's criteria were 56% and 62%, respectively, and 55% and 63%,
      as defined by Nugent's criteria. This is the first study to report cure rates for
      women with 'intermediate' wet smear ratings according to Nugent's classification
      and this group had an overall cure rate of 44%. The cure rate of treatment of
      bacterial vaginosis was not improved by using lactobacilli-prepared tampons for
      one menstruation.

PMID- 15848991
TI  - Drug-induced hypersensitivity syndrome associated with cytomegalovirus
      reactivation: immunological characterization of pathogenic T cells.
AB  - We report a case of tribenoside-induced hypersensitivity syndrome associated with
      cytomegalovirus reactivation and investigation of the immunological
      characteristics of the circulating and skin-infiltrating lymphocytes. Activated
      CD8+ T cells outnumbered CD4+ cells in both the circulation and the skin lesions.
      Upon in vitro stimulation with the drug, CD4+ cells proliferated and produced
      interferon-gamma. The circulating CD8+ cells used limited T-cell receptor Vbetas,
      some of which are restricted to cytomegalovirus-derived peptide in the context of
      the HLA-A2 haplotype. CD8+ cells and cytomegalovirus-containing cells closely co
      localized in the skin lesions. These results suggested that CD4+ cells were drug
      reactive, whereas cytomegalovirus activated CD8+ cells in the present case. These
      two cell types seemed to play a distinct role in drug-induced hypersensitivity
      syndrome.

PMID- 15848992
TI  - Ichthyosis follicularis with alopecia and photophobia in a girl with cataract:
      histological and electron microscopy findings.
AB  - A rare congenital ectodermal disorder characterized by ichthyosis follicularis,
      alopecia and photophobia has been designated the acronym IFAP. An X-linked
      recessive mode of inheritance was initially proposed but a few recent reports in
      girls suggested genetic heterogeneity of this syndrome. We herein describe a 3
      year-old girl with clinical and histological features typical of IFAP. In
      addition to the already known features of the syndrome the patient also developed
      bilateral cataract. Electron microscopy examination of the skin showed partial
      disruption of the intercellular bridges, spongiotic changes and decrease in the
      number and size of desmosomes supporting the notion that IFAP may be a cell-to
      cell adhesion disorder.

PMID- 15848993
TI  - Digital skin necrosis in congenital afibrinogenaemia associated with hepatitis C
      virus infection, mixed cryoglobulinaemia and anticardiolipin antibodies.
AB  - Congenital afibrinogenaemia is a rare genetic disorder transmitted as an
      autosomal recessive trait and characterized by the complete absence of fibrinogen
      in the plasma. We report a 41-year-old woman who suffered from congenital
      afibrinogenaemia and hepatitis C viral infection and presented with ischaemic
      necrosis and livedo of the toes. Laboratory investigations showed the presence of
      mixed cryoglobulinaemia and anticardiolipin antibodies. Resolution occurred with
      plasmapheresis. We discuss the pathophysiology of this unusual condition and
      review the literature for skin manifestations associated with this rare
      haemostasis disorder.

PMID- 15848994
TI  - Metastatic Crohn's disease mimicking genital pyoderma gangrenosum in an HIV
      patient.
AB  - The differential diagnosis of ulcerative genital lesions in patients with high
      risk sexual habits can be a challenge even for dermatologists. We present the
      case of a 27-year-old HIV-positive male with a history of recalcitrant genital
      ulcers. Microbiology studies were negative. A skin biopsy and a sample from a
      perineal fistula showed granulomatous infiltrates. The patient was treated with
      prednisone, metronidazole and aminosalicylates, showing complete resolution of
      the lesions in a few weeks. The clinical picture and histological findings are
      consistent with the diagnosis of cutaneous metastatic Crohn's disease. Although
      infrequent, metastatic Crohn's disease should be suspected in cases of
      recalcitrant ulcerative conditions, even in the absence of intestinal disease.

PMID- 15848995
TI  - Daclizumab: a novel therapeutic option in severe bullous pemphigoid.

PMID- 15848996
TI  - Serum levels of vitamin B12 and folate in Korean patients with vitiligo.

PMID- 15848997
TI  - Psychiatric tests in seborrhoeic dermatitis.

PMID- 15848998
TI  - Doubtful value of patch testing for suspected contact allergy to ophthalmic
      products.

PMID- 15848999
TI  - Perineurial and vascular calcification in a patient with chronic renal failure.

PMID- 15849000
TI  - Prognosis of acute urticaria in children.

PMID- 15849001
TI  - Exaggerated insect bite-like reaction in patients affected by oncohaematological
      diseases.

PMID- 15849002
TI  - Telogen effluvium caused by magnesium valproate and lamotrigine.

PMID- 15849003
TI  - Merkel-cell carcinoma in Behcet's disease.

PMID- 15849004
TI  - Breast cancer of the axillary extension.

PMID- 15849005
TI  - Generalized vitiligo after allogeneic bone marrow transplantation.

PMID- 15849006
TI  - Pemphigus improving with gluten-free diet.

PMID- 15849007
TI  - Extensive basal cell carcinoma and disseminated lesions in Hand-Schuller
      Christian disease.

PMID- 15849008
TI  - Giant molluscum contagiosum: does it affect truly immunocompetent individuals?

PMID- 15849009
TI  - Multiple autoimmune syndrome in a patient with pemphigus vulgaris.

PMID- 15849010
TI  - Fulminant papulopustular tinea corporis caused by Trichophyton mentagrophytes.

PMID- 15849013
TI  - DNA microarrays and expression profiling in drug abuse research.

PMID- 15849014
TI  - Microarrays--the challenge of preparing brain tissue samples.
AB  - Microarray experiments allow researchers to collect an amazing amount of gene
      expression data that have the potential to provide unique information to help
      interpretation of the biological functions of the central nervous system. These
      experiments are, however, technically demanding and present unique difficulties
      when used in the context of neuroscience research, in particular. Success or
      failure of microarray experiments are highly dependent on reproducible target
      preparations. This involves a relatively long chain of preparation steps, such as
      removal of tissue from experimental animals or from post-mortem human brains,
      storage, selection, and excision of brain regions. This is followed by RNA
      extraction, reverse transcription, and labeling of target cDNAs or cRNAs.
      Additionally, it is emphasized that the quality of microarray data largely relies
      on the proper handling of animals throughout experiments and the time of the day
      when experiments are stopped. This article tries to provide hints for some basic
      rules to be observed in preparation of samples for expression profiling studies.

PMID- 15849015
TI  - Issues for consideration in the analysis of microarray data in behavioural
      studies.
AB  - Microarrays are one of several technologies that allow for measurement the
      expression of thousands of genes simultaneously. This technological advance
      provides a challenge for the analysis of these data. In this review we discuss
      these analytical issues from the initial quality control to normalization,
      differential expression, clustering and finally functional pathway analysis. We
      focus on Affymetrix data but many of the issues are the same for other array
      platforms.

PMID- 15849016
TI  - Statistical analysis of microarray data.
AB  - Microarrays promise dynamic snapshots of cell activity, but microarray results
      are unfortunately not straightforward to interpret. This article aims to distill
      the most useful practical results from the vast body of literature available on
      microarray data analysis. Topics covered include: experimental design issues,
      normalization, quality control, exploratory analysis, and tests for differential
      expression. Special attention is paid to the peculiarities of low-level analysis
      of Affymetrix chips, and the multiple testing problem in determining differential
      expression. The aim of this article is to provide useful answers to the most
      common practical issues in microarray data analysis. The main topics are pre
      processing (normalization), and detecting differential expression. Subsidiary
      topics include experimental design, and exploratory analysis. Further discussion
      is found at the author's web page (http://discover.nci.nih.gov --> Notes on
      Microarray Data Analysis).

PMID- 15849017
TI  - Expression profiling methods used in drug abuse research.
AB  - A variety of analytical methodologies to investigate gene expression patterns in
      cells or tissues have been developed. For screening purposes, a large number of
      target mRNAs have to be interrogated simultaneously. These requirements have been
      met more or less comprehensively by Differential Display (DD) RT-PCR, Suppression
      Subtractive Hybridization (SSH), Serial Analysis of Gene Expression (SAGE), and
      DNA chips. The ultimate goal to cover any gene transcript potentially expressed
      by a given cell is on the way to be achieved by microbead arrays and by
      Affymetrix gene chips. Once targets of interest are identified, techniques
      employing low degrees of multiplexing, such as RNAse protection assays or some
      bead-based techniques (Luminex) eventually provide extremely fast results on the
      diagnostic level. With the aid of powerful computer programs, expression
      profiling technologies have opened intriguing new insights into the complex world
      of gene regulation. These new techniques have also been applied in drug abuse
      research recently and some examples of such approaches are described.

PMID- 15849018
TI  - Expression profiling and QTL analysis: a powerful complementary strategy in drug
      abuse research.
AB  - Alcoholism is a complex disease exhibiting a multifactorial mode of transmission.
      To simplify the genetic and phenotypic complexity of the alcoholic phenotype,
      alcohol-preferring (P) and -non-preferring (NP) rats were developed on the basis
      of alcohol preference and consumption as an animal model of alcoholism. Total
      gene expression analysis (TOGA) and quantitative trait loci (QTL) analysis were
      applied to selectively bred, inbred P and NP rats as complementary studies to
      identify genetic factors that contribute to alcohol preference and consumption.
      TOGA analysis was utilized to screen for differential expression in several brain
      regions involved in the mesocorticolimbic dopamine (DA) system. Genes exhibiting
      differences in expression were then screened for an association to the alcohol
      preference phenotype, the quantitative trait of a previously identified QTL. By
      evaluating differences in gene expression for linkage to a quantitative trait,
      this combined approach was implemented to identify alpha-synuclein, a candidate
      gene for alcohol preference.

PMID- 15849019
TI  - Using in vitro models for expression profiling studies on ethanol and drugs of
      abuse.
AB  - The use of expression profiling with microarrays offers great potential for
      studying the mechanisms of action of drugs of abuse. Studies with the intact
      nervous system seem likely to be most relevant to understanding the mechanisms of
      drug abuse-related behaviours. However, the use of expression profiling with in
      vitro culture models offers significant advantages for identifying details of
      cellular signalling actions and toxicity for drugs of abuse. This study discusses
      general issues of the use of microarrays and cell culture models for studies on
      drugs of abuse. Specific results from existing studies are also discussed,
      providing clear examples of relevance for in vitro studies on ethanol, nicotine,
      opiates, cannabinoids and hallucinogens such as LSD. In addition to providing
      details on signalling mechanisms relevant to the neurobiology of drugs of abuse,
      microarray studies on a variety of cell culture systems have also provided
      important information on mechanisms of cellular/organ toxicity with drugs of
      abuse. Efforts to integrate genomic studies on drugs of abuse with both in vivo
      and in vitro models offer the potential for novel mechanistic rigor and
      physiological relevance.

PMID- 15849020
TI  - Gene expression in animals with different acute responses to ethanol.
AB  - The genetic and environmental contributions to differences in response to ethanol
      have been examined widely using inbred strains, selected lines and genetically
      engineered (transgenic and 'knock-out') animals. In addition, recombinant inbred
      strains have been used to identify QTLs (chromosomal regions) associated with
      particular responses to ethanol. If the polymorphism that underlies such a QTL is
      localized within the regulatory region of a gene, it could alter the level or
      stability of the gene product (transcript). This possibility can be addressed by
      measuring mRNA levels in brains (or other tissue) of inbred or selected lines of
      animals using DNA microarray technology. In this paper, we review microarray
      studies conducted in animals that differ in their responses to ethanol. The
      results of these studies point out the critical nature of the experimental
      design, statistical analyses and 'filtering' procedures for producing
      interpretable data and identifying candidate genes. In particular, the
      determination of differentially expressed genes between selected lines of
      animals, and the localization of the differentially expressed genes within QTLs
      for the selected phenotype, dramatically increases the probability of identifying
      genes that contribute to that phenotype through differential expression.
      Microarray analysis can also be used to assess changes in gene expression that
      accompany transgene introduction and/or gene 'knock-out', which may modulate the
      influence of the targeted gene on behaviour.

PMID- 15849021
TI  - The search for candidate genes of alcoholism: evidence from expression profiling
      studies.
AB  - Alcoholism is the outcome of complex interactions between the environment and
      multiple gene loci, which may encode pre-existing susceptibility, or contribute
      to the neuroadaptations underlying the process of developing dependence. Because
      of this, the prospect of simultaneous, genome wide, high-throughput analysis of
      gene expression allowed by microarray technology has met with great expectations.
      The hope has been that new insights into pathogenesis of substance disorders will
      rapidly be gained, leading to identification of novel treatment targets. The
      usefulness of this approach as a discovery tool in addiction research will be
      critically reviewed here. In this article, we describe the evolution of our
      experimental approaches, from first generation Affymetrix expression arrays to
      present high-density arrays, and from the use of original Affymetrix software to
      more advanced analysis of the probe signal, and different statistical approaches
      to creating candidate gene lists. Further, we address some methodological issues
      critical to the study of brain samples by microarray technology. We also
      summarize findings from several expression profiling experiments involving
      different animal models of alcoholism. The accumulation of expression data from
      different animal models allows mining the database for patterns of overlap. Such
      second level analysis depends on the generation of uniform and reliable datasets.

PMID- 15849022
TI  - Morphine-induced changes of gene expression in the brain.
AB  - Repeated opiate administration alters gene expression in different brain regions
      of rodents, an effect which may contribute to plastic changes associated with
      addictive behaviour. There is increasing evidence that multiple transcription
      factors are induced in morphine tolerance, sensitization and during morphine
      withdrawal. Whereas morphine treatment does not lead to major alterations in the
      expression of mu-opioid receptors (MOR), there is transcriptional regulation of
      proteins involved in MOR trafficking such as GRK2 or beta arrestin 2 as well as
      altered expression of other receptors such as dopamine receptors, NMDA receptors,
      GABA(A) receptor and alpha(2A) adrenoceptor. Recent gene expression profiling
      studies reveal additional clusters of morphine-responsive genes: whereas single
      dose administration has been shown to predominantly reduce expression of genes
      involved in metabolic function, ascending morphine doses leading to morphine
      tolerance revealed induction of genes which alter patterns of synaptic
      connectivity such as arc or ania-3. These genes remained elevated after
      precipitated withdrawal, which also triggered the expression of several
      transcriptional activators and repressors. In addition, morphine has been shown
      to be a strong inducer of heat shock protein 70, a cell protective protein which
      might counter-regulate opiate-induced neurotoxicity. Temporal expression profiles
      during a chronic morphine application schedule revealed discrete and fluctuating
      expression of gene clusters such as transcription factors, G-protein-coupled
      receptors and neuropeptides. Prolonged abstinence seems to be characterized by up
      regulation of several transcription factors and persistent down-regulation of
      ligand gated ion channels such as glutamatergic and GABA-ergic receptor subunits.
      These long-term changes in receptor expression suggest a persistent alteration of
      synaptic signalling after morphine treatment.

PMID- 15849023
TI  - Long-term gene expression in the nucleus accumbens following heroin
      administration is subregion-specific and depends on the nature of drug
      administration.
AB  - Repeated exposure to addictive drugs results in long-lasting neuroadaptations in
      the brain, especially in the mesocorticolimbic system. Within this system, the
      nucleus accumbens (NAc) plays a major integrative role. As such, the NAc has been
      shown to be a target of short- and long-lasting drug-induced neuroadaptations at
      the levels of neurotransmission and cellular morphology. The long-lasting
      neuroadaptations might depend critically on alterations in gene expression.
      Recently, we obtained a set of transcripts by means of subtractive hybridization,
      of which the expression was decreased in the rat NAc shell after long-term
      extinction of intravenous heroin self-administration. Interestingly, the majority
      of these transcripts were also down-regulated upon long-term extinction of
      cocaine self-administration. Using the yoked-control operant paradigm, it was
      shown that non-contingent administration of these drugs resulted in a totally
      different gene expression profile. However, in the rat NAc core, both self
      administration and non-contingent heroin administration induced a qualitatively
      similar expression profile. Hence, cognitive processes associated with drug self
      administration seem to direct the long-term genomic responses in the NAc shell,
      whereas the NAc core might primarily mediate the persistent pharmacological
      effects of addictive drugs (including Pavlovian conditioning).

PMID- 15849024
TI  - Microarray studies of psychostimulant-induced changes in gene expression.
AB  - Alterations in the expression of multiple genes in many brain regions are likely
      to contribute to psychostimulant-induced behaviours. Microarray technology
      provides a powerful tool for the simultaneous interrogation of gene expression
      levels of a large number of genes. Several recent experimental studies, reviewed
      here, demonstrate the power, limitations and progress of microarray technology in
      the field of psychostimulant addiction. These studies vary in the paradigms of
      cocaine or amphetamine administration, drug doses, route and also mode of
      administration, duration of treatment, animal species, brain regions studied and
      time of tissue collection after final drug administration. The studies also
      utilize different microarray platforms and statistical techniques for analysis of
      differentially expressed genes. These variables influence substantially the
      results of these studies. It is clear that current microarray techniques cannot
      detect small changes reliably in gene expression of genes with low expression
      levels, including functionally significant changes in components of major
      neurotransmission systems such as glutamate, dopamine, opioid and GABA receptors,
      especially those that may occur after chronic drug administration or drug
      withdrawal. However, the microarray studies reviewed here showed cocaine- or
      amphetamine-induced alterations in the expression of numerous genes involved in
      the modulation of neuronal growth, cytoskeletal structures, synaptogenesis,
      signal transduction, apoptosis and cell metabolism. Application of laser capture
      microdissection and single-cell cDNA amplification may greatly enhance microarray
      studies of gene expression profiling. The combination of rapidly evolving
      microarray technology with established methods of neuroscience, molecular biology
      and genetics, as well as appropriate behavioural models of drug reinforcement,
      may provide a productive approach for delineating the neurobiological
      underpinnings of drug responses that lead to addiction.

PMID- 15849025
TI  - Gene expression profiling in the brains of human cocaine abusers.
AB  - Chronic cocaine abuse induces long-term neurochemical, structural and behavioural
      changes thought to result from altered gene expression within the nucleus
      accumbens and other brain regions playing a critical role in addiction. Recent
      methodological advances now allow the profiling of gene expression in human
      postmortem brain. In this article, we review studies in which we have used
      Affymetrix oligonucleotide microarrays to identify transcripts that are
      differentially expressed in the nucleus accumbens of cocaine abusers in
      comparison to well-matched control subjects. Of the approximately 39,000 gene
      transcripts interrogated, the expression of only a fraction of 1% is
      significantly modified in cocaine abusers. Found within this list are equivalent
      incidences of increased and decreased transcript abundance, including known gene
      transcripts clustered into several functional categories. A striking exception is
      a group of myelin-related genes, consisting of multiple transcripts representing
      myelin basic protein (MBP), proteolipid protein (PLP) and myelin-associated
      oligodendrocyte basic protein (MOBP), which as a group are substantially
      decreased in cocaine abusers compared to controls. These data, suggesting a
      possible dysregulation of myelin in cocaine abusers, are discussed in the context
      of myelin-related changes in other human brain disorders. Finally, the effects of
      cocaine abuse on the profile of gene expression in some other brain regions
      critical for addiction (the prefrontal cortex and ventral midbrain) are briefly
      reviewed.

PMID- 15849026
TI  - Left-handers have a lower prevalence of arthritis and ulcer.
AB  - In a very large study (N = 1,247,344), left-handedness showed no association with
      allergies overall (and an inconsistent association with individual allergies),
      but there was strong evidence that left-handers had lower rates of arthritis and
      ulcer--Arthritis: Odds-ratio (OR) = 0.942, 95% CI 0.922-0.962; Ulcer: OR = 0.920,
      95% CI 0.896-0.944.

PMID- 15849027
TI  - Nostril dominance: differences in nasal airflow and preferred handedness.
AB  - Because there appears to be a general propensity among many people to have a
      consistency in the sidedness of their lateral preferences, the purpose of the
      present study was to determine if this consistency extends to the airflow through
      the individual nostrils as well. To test for this, hot wire anemometers measured
      the airflow in each nostril at 15-minute intervals for 6 continuous hours in 11
      right-handed and 9 left-handed adult males. Participants also provided self
      reports of which nostril appeared to have the greater airflow. The airflow
      measurements supported the hypothesis of a handedness by nostril interaction, in
      that left-handers more often experienced greater airflow in their left nostrils
      whereas right-handers showed the opposite pattern. Self-reports were not an
      especially reliable measure of nasal patency. In most subjects the same nostril
      was not always the more open one. This left/right shifting of the more patent
      nostril is termed the nasal cycle. This study also provides the first data
      comparing the nasal cycle patterns of left-handers and right-handers.

PMID- 15849028
TI  - Semantic activation within and across the cerebral hemispheres: what's left isn't
      right.
AB  - This study examined differences in the spread of semantic activation within and
      between the cerebral hemispheres. A lateralised lexical decision task using
      indirect priming was presented to 58 undergraduates with primes and targets
      separated by 215 or 750 milliseconds (ms). Prime and target words were presented
      to the same or opposite visual fields and were either directly related (book
      read), indirectly related (lion-[tiger]-stripes), or unrelated (cup-street). At
      215 ms participants exhibited significant priming effects to directly related
      words in all conditions except when primes and targets were both presented to the
      right hemisphere (RH). In contrast, priming to indirectly related words was
      effective only when primes and targets were presented to opposite hemispheres. At
      750 ms, significant priming occurred for directly related words in all
      conditions, and for indirectly related words when primes were presented to the
      RH. Results suggest that priming for directly and indirectly related concepts
      occurs unilaterally in each hemisphere before 215 ms. Both prime types activate
      semantic networks in the RH within 750 ms, whereas the LH processes information
      in a more focused manner. This suggests that activation spreads contralaterally
      from each hemisphere first to directly and then to indirectly related concepts,
      indicating the importance of incorporating contralateral priming contrasts in
      lexical decision tasks.

PMID- 15849029
TI  - Hemispheric asymmetry and deception detection.
AB  - Previous research has indicated a possible right hemisphere advantage in
      deception detection including a possible left ear advantage in decoding deceptive
      statements. In this study, 32 undergraduate students listened to 112 true and
      false statements presented unilaterally to both the left and right ears. The
      participants responded using their left or right hand, indicating whether the
      statements they heard were true or false. It was found that there was a
      significant (p < .004) advantage for the left ear in detecting whether a
      statement was true or false. These findings replicate and extend previous
      research indicating a left ear/right hemisphere advantage in deception detection.

PMID- 15849030
TI  - Chimpanzees are right-handed when recording bouts of hand use.
AB  - Whether nonhuman primates exhibit population-level handedness remains a topic of
      considerable debate. Previous research has shown that chimpanzees are right
      handed when frequencies of hand use are recorded but some have questioned the
      validity of this approach. In this study, we evaluated handedness in 180 captive
      chimpanzees for a task measuring bimanual actions. Bouts rather than frequency of
      hand use were recorded in each subject. Population-level right-handedness was
      found using both continuous and nominal scales of measurement. Neither sex nor
      rearing history had a significant effect on hand use. These results indicate that
      chimpanzees are right-handed, even when using a more conservative measure of
      handedness. Limitations in the use of bouts in handedness assessment are also
      discussed.

PMID- 15849031
TI  - Emotion words are remembered better in the left ear.
AB  - In dichotic listening studies, numerous investigators have shown a left ear
      advantage (i.e., right hemisphere superiority), when judging emotional tone of
      speech. In the present study, dichotic word-pairs of emotion and non-emotion
      words were presented to participants who were instructed to recall the entire
      list in each block. Unlike other studies in which participants responded to
      emotional intonations, participants in the present investigation listened to
      stimuli that were spoken in a neutral intonation. A total of 62 participants
      listened to emotion (e.g., loving) and non-emotion (e.g., combine) words that
      were dichotically presented. The results showed a left ear advantage for emotion
      words. This finding provides strong support for the right-hemisphere hypothesis
      in the form of a stronger memory for emotion words presented to the left ear. The
      findings are consistent with the role of the right hemisphere in the perception
      of emotional information.

PMID- 15849032
TI  - Manual skill, hand skill asymmetry, and neuropsychological test performance in
      schoolchildren with spastic cerebral palsy.
AB  - Bilateral hand skill assessment with a computerised version of the Peg Moving
      Task, and neuropsychological testing, were performed in 30 children aged 7 to 8
      years with spastic cerebral palsy (CP) and without mental retardation, diplegia
      (n = 10), right hemiplegia (n = 10), or left hemiplegia (n = 10), and in 30
      controls. Compared to controls: (i) 30% of the hemiplegic children showed
      impairment of the unaffected hand and 70% of the diplegic children showed
      impairment in both hands; (ii) children with CP were impaired only in oral
      repetition and in visual-motor tasks. Results of neuropsychological testing were
      not significantly different between the three groups of children with CP. Right
      minus left asymmetry in hand skill was not related to neuropsychological testing;
      however, degree of impairment of the right hand was associated with phonological
      and metaphonological skills, and of the left hand with visuospatial and counting
      performance. Hand skill was related to the ability to perform many daily living
      manual activities. It is concluded that impairment of hand function, rather than
      the side of the more affected hand, is related to neuropsychological deficits in
      children with cerebral palsy.

PMID- 15849033
TI  - Hand preference, magical thinking and left-right confusion.
AB  - Several reports suggest a significant correlation between hand preference
      quotients and Magical Ideation Scale (MIS) scores, such that individuals with
      mixed preferences have higher MIS scores. In a sample of 156 male and 257 female
      undergraduate university students no significant correlation was found between
      MIS scores and hand preference; hand preference being defined in numerous ways,
      and using short and long hand preference questionnaires to assess handedness. An
      index of left-right confusion was significantly related to MIS score, but only in
      females. We suggest that the role of subjects' response style and general
      approach to filling out questionnaires should be fully explored before
      "neurological" causes of links between hand preference and other questionnaire
      assessed behavioural variables are invoked.

PMID- 15849047
TI  - Successful management of severe group A streptococcal soft tissue infections
      using an aggressive medical regimen including intravenous polyspecific
      immunoglobulin together with a conservative surgical approach.
AB  - Intravenous polyspecific immunoglobulin G (IVIG) has been reported to be
      efficacious as adjunctive therapy in patients with toxic shock syndrome caused by
      a group A streptococci (GAS). GAS is also an important cause of necrotizing
      fasciitis, for which an early and extensive surgical intervention is currently
      advocated. Here we report on the use of an aggressive medical regimen including
      high-dose IVIG together with a conservative surgical approach in severe GAS soft
      tissue infection. We describe 7 patients with severe soft tissue infection caused
      by GAS, who all were treated with effective antimicrobials and high-dose IVIG.
      Surgery was either not performed or only limited exploration was carried out. Six
      of the patients had toxic shock syndrome. All patients survived. Immunostaining
      of tissue biopsies from 2 of the patients revealed high levels of GAS,
      superantigen and pro-inflammatory cytokines initially, which were dramatically
      reduced in a repeat biopsy of the initial operative site collected from 1 of the
      patients 66 h post-IVIG administration. The study suggests that the use of a
      medical regimen including IVIG in patients with severe GAS soft tissue infections
      may allow an initial non-operative or minimally invasive approach, which can
      limit the need to perform immediate wide debridements and amputations in unstable
      patients.

PMID- 15849048
TI  - Successful treatment of Staphylococcus epidermidis prosthetic valve endocarditis
      with linezolid after failure of treatment with oxacillin, gentamicin, rifampicin,
      vancomycin, and fusidic acid regimens.
AB  - We present a 49-y-old male, with a history of Marfan's disease and aortic and
      mitral valve replacement surgery, who was operated for a type III
      thoracoabdominal aneurysm. The postoperative course was compromised by a
      Staphylococcus epidermidis mitral valve endocarditis, which was successfully
      treated only after intravenous linezolid was included in the therapy.

PMID- 15849049
TI  - Nosocomial bloodstream infections in children and adolescents in southern Israel:
      a 10-year prospective study (1992-2001).
AB  - We studied the epidemiology, microbiology, clinical presentation and outcome of
      nosocomial bloodstream infections (NBI) in children and adolescents in southern
      Israel during 1992-2001. Information on NBI was collected prospectively by active
      surveillance. NBI was diagnosed when a clinically significant positive blood
      culture was drawn in a patient during >48 h after admission. 469 episodes
      occurred in 370 children and adolescents aged 1 m-18 y. The overall incidence of
      NBI was 5.3/1000 patients, with no increase during the study period. A
      significant decrease in NBI incidence was recorded at the neonatal intensive care
      unit (NICU) during 1997-2001 vs 1992-1996. The incidences of NBI at the
      paediatric ICU (PICU), paediatric wards and paediatric surgery departments (PSD)
      were 24.1, 2.8 and 2.5/1000 patients, with an increase in NBI cases at PICU and
      PSD during 1997-2001 vs 1992-1996. Of 661 pathogens, Gram-negative, Gram-positive
      and fungal organisms were isolated in 54.3%, 36.6% and 9.1% of cases,
      respectively. Enterobacteriaceae (34.6% of all isolates) were the most frequently
      isolated Gram-negative organisms. Enterococcus spp., coagulase-negative
      staphylococci and Staphylococcus aureus (9.5% of all isolates each) were the most
      frequently isolated in Gram-positive organisms. A significant increase was
      recorded in the incidence of NBI caused by Streptococcus pneumoniae and
      Pseudomonas spp. A significant decrease in the susceptibility of
      Enterobacteriaceae spp. to piperacillin, ceftazidime, gentamicin and ceftriaxone
      was recorded during the study period. 33 (8.9%) patients with NBI died.

PMID- 15849050
TI  - Endogenous endophthalmitis: a 13-year review at a tertiary hospital in South
      Australia.
AB  - This retrospective report presents a series of patients with endogenous
      endophthalmitis treated over a 13-y period in a tertiary care centre in South
      Australia. 16 eyes of 13 patients (8 M, 5 F) with a mean age 62 y were included.
      Systemic predisposing risk factors were mainly diabetes mellitus (30.7%), chronic
      obstructive airway disease (23.1%) and end-stage renal disease (15.4%). Isolated
      organisms included fungal species in 11 eyes (7 eyes with Candida albicans and 4
      with Aspergillus fumigatus), Gram-positive isolates in 4 eyes, and Pseudomonas
      aeruginosa in 1 eyes. Presenting visual acuity was 20/200 or lower in 8 patients
      (61.5%). Final visual improvement of more than 2 lines was noted in 5 patients,
      it was stable or worse in 6 patients and in 2 patients the eye was either
      enucleated or eviscerated. Systemic aspergillosis resulted in death of both
      patients. In conclusion, the clinical course and microbiological profile of
      pathogens in patients with endogenous endophthalmitis in our series are similar
      to other recent western reports. Candida species are the leading isolates, with
      an overall poor visual prognosis, especially in Aspergillus infections. Close
      monitoring of immune-compromised patients with systemic infections may enable
      early diagnosis and treatment and improve prognosis.

PMID- 15849051
TI  - Brain stem encephalitis in listeriosis.
AB  - Serious infection with the bacterium L. monocytogenes mainly manifests as sepsis
      and/or meningitis. A particular entity is Listeria brain stem encephalitis, which
      is characterized by progressive brain stem deficits. The condition is fatal
      unless early treated. The purpose of the present study was to assess the
      incidence of brain stem encephalitis in a population-based listeriosis material.
      Medical records from 212 of the 240 patients with serious listeriosis reported in
      Norway from 1977 to 2000, as well as autopsy material from 8 of these patients,
      were available. This material was searched for clinical and neuropathological
      evidence of brain stem infection. Findings indicating brain stem encephalitis
      were present in 19 of the 172 patients with adult listeriosis (11%) but none of
      the 40 pregnancy-related listeriosis cases. None of the 19 patients had been
      diagnosed with Listeria brain stem infection originally. We conclude that brain
      stem encephalitis is relatively common in this Norwegian listeriosis material.

PMID- 15849052
TI  - Treatment of pan-drug resistant Acinetobacter baumannii.
AB  - The objective of this study was to investigate the role of sulbactam in the
      treatment of pan-drug resistant Acinetobacter baumannii (PDRAB). We studied 89
      patients with PDRAB infection treated with different antibiotic regimens. Group A
      (n = 39) were treated with carbapenem with sulbactam and group B (n = 30) with
      second and third generation cephalosporins, antipseudomonas penicillins, or
      fluoroquinolones with aminoglycosides. We also studied the MICs for 48 PDRAB
      strains by using antimicrobial agents with and without sulbactam. The clinical
      outcomes of the 2 groups did not differ significantly, either in terms of
      resolution of infection (25/59, 42% in group A vs 12/30, 40% in group B) or
      survival (35/59, 59% vs 17/30, 57%). However, the MICs indicated that 16 of the
      48 strains were sensitive to imipenem/sulbactam, compared with only 2 of the 48
      to imipenem alone. The addition of sulbactam thus reversed the response in 30%
      (14/46) of strains initially resistant or only intermediate sensitive to
      imipenem. The MICs for meropenem/sulbactam were in the sensitive range for 8 of
      48 strains compared to only 3 of the meropenem alone, indicating an 11% (5/45)
      reversal rate when sulbactam was added to meropenem. For the 38 isolates
      initially resistant to both carbapenems alone, imipenem/sulbactam reversed the
      resistance in 16% (6/38), while meropenem/sulbactam did so in only 3% (1/38).
      Thus, the carbapenem-sulbactam combinations did not clearly improve clinical
      outcome, but they did demonstrate lower MICs for the PDRAB strains tested. It may
      be that aggressive, early treatment of A. baumannii infections with these agents
      might prevent the emergence of PDRAB strains.

PMID- 15849053
TI  - A nosocomial sapovirus-associated outbreak of gastroenteritis in adults.
AB  - The human caliciviruses norovirus and sapovirus are leading causes of acute, non
      bacterial gastroenteritis. In contrast to norovirus, sapovirus is known to give
      infections mainly in infants and young children. We describe a nosocomial
      outbreak of gastroenteritis associated with sapovirus involving 23 adult patients
      and medical staff. The mean age of the patients and medical staff was 52 y and
      the major signs and symptoms were nausea, diarrhoea, vomiting, abdominal cramp,
      headache, myalgia and fever. More patients had diarrhoea (72%) than vomiting
      (56%) and the mean duration of symptoms was 6 d. A secondary attack rate of 45%
      was seen affecting in all 10 persons with a mean age of 29 y. Sequences of the
      capsid gene revealed a 97% nucleotide homology to the sapovirus genogroup IV
      reference strain Chiba/000671T/1999. This is one of the first reported nosocomial
      outbreaks of sapovirus infection among adults and shows that a diagnostic test
      for sapovirus should be included in investigation of gastroenteritis among
      adults.

PMID- 15849054
TI  - Protozoal forms in the sputum of immunocompromized patients.
AB  - The aim of this study is to determine whether, in situations of marked
      immunological deficit, principally among patients with AIDS, there is a greater
      frequency of protozoal forms. Comparative study was of 2 group of patients, 1 an
      immunocompromized group, main HIV+, and the other a non-immunocompromized group
      with different respiratory disorders (control group). A cytological study was
      carried out using 295 sputum smears, obtained between 1994 and 2003, from
      patients at the Central University Hospital of Asturias, Spain. Smears were valid
      for 106 patients, 83 of whom presented HIV infection. Protozoa were detected in
      72 of this group. Our findings indicate a greater number of protozoal forms in
      the sputa of patients with AIDS than among the other 2 groups analysed (patients
      without AIDS and control group).

PMID- 15849055
TI  - Intestinal parasitic infections in HIV/AIDS patients: experience at a teaching
      hospital in central Brazil.
AB  - In order to verify the occurrence of intestinal parasitic infections in human
      immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients,
      100 HIV/AIDS patients (Group 1) and 85 clinically healthy individuals (Group 2)
      were submitted to coproparasitological examination. Intestinal parasites were
      detected in 27% of patients from Group 1 and in 17.6% from Group 2. In Group 1
      the most frequent parasites were Strongyloides stercoralis (12%), with 2 cases of
      hyperinfection; Isospora belli, 7%; Cryptosporidium sp., 4%; with 1 asymptomatic
      case and hookworm, 4%. Of the infected patients from Group 1 who reported to be
      chronic alcoholics, 64.3% had strongyloidiasis. Only 6 of the 27 infected
      patients from Group 1 were on highly antiretroviral therapy (HAART). In Group 2
      the most frequent parasites were S. stercoralis, 7.1%; hookworm, 7.1% and Giardia
      lamblia, 3.5%. In conclusion, diagnosing intestinal parasites in HIV/AIDS
      patients is necessary especially in those who report to be chronic alcoholics or
      are not on antiretroviral treatment.

PMID- 15849056
TI  - Comparison of intuitive versus systematic strategies for aetiological diagnosis
      of pericardial effusion.
AB  - In an attempt to elucidate better the various aetiologies of pericardial
      effusion, we developed a diagnostic protocol that incorporated a battery of
      systematic tests including blood cultures, throat swab cultures and serological
      tests for various infectious agents and estimation of serum antinuclear
      antibodies and serum thyroid-stimulating hormone. Over a 2-y period ending May
      2000, we evaluated prospectively and diagnostic usefulness of our strategy in a
      cohort (n = 136) of patients with pericardial effusion treated at Hospital Timone
      (HT), Marseille. We compared our findings with those observed in a
      retrospectively (May 1998-May 2000) drawn cohort (n = 127) of patients treated at
      Hospital Louis Pradel (HLP), Lyon and in which the laboratory investigation
      towards establishing an aetiological diagnosis was undertaken intuitively.
      Overall, the aetiologies were obvious clinically in 18% of cases. In other cases,
      specific aetiologies (27.3% vs 3.9%; p < 0.001), including treatable conditions
      (11.1% vs 2.4%; p < 0.001) were identified significantly more frequently in the
      HT cohort compared to the HLP cohort. The diagnosis strategy we propose may be
      helpful in elucidating the aetiological diagnosis of pericardial effusion when a
      cause is not obvious clinically.

PMID- 15849057
TI  - A fourth dose of DTPa-IPV vaccine given to 4-6 year old children in Italy and
      Sweden following primary vaccination at 3, 5 and 11-12 months of age.
AB  - Healthy 4-6 y old children from Italy and Sweden immunized with DTPa and
      inactivated or oral polio vaccines at 3, 5 and 11-12 months of age, received 1
      dose of combined DTPa-IPV (n = 211) or DTPa + IPV as separate doses (n = 205) in
      a randomized trial. The pre-booster seroprotection rates were similar in each
      group and were above 60% against all antigens except diphtheria (31.3% and 37.0%)
      and PT (21.5% and 25.9%) in the DTPa-IPV and DTPa + IPV groups, respectively. At
      least 99.5% of subjects had seroprotective antibody levels against diphtheria,
      tetanus and polioviruses and > or = 96% showed a vaccine response to each
      pertussis antigen after vaccination. Post-booster antibody levels increased at
      least 51-fold for anti-diphtheria and anti-tetanus, at least 18-fold for anti
      pertussis antibodies and at least 32-fold for antibodies against all 3 poliovirus
      types, compared to prior levels. DTPa-IPV was comparable to DTPa + IPV in terms
      of seroprotection rates and mean antibody levels against each vaccine antigen.
      Similar reactogenicity profiles were observed between groups including swelling >
      50 mm [13% (9.1, 18.7) vs 17% (12.4, 23.4)] or involving an adjacent joint [0% (
      ,-) vs 1.5% (0.3, 4.3)] and were consistent with previous reports. The combined
      DTPa-IPV vaccine could be used to add DTP valences to the IPV vaccine currently
      given to children in Scandinavia and Italy at 4-6 y of age and reinforce
      protection against 4 diseases.

PMID- 15849058
TI  - Clostridium tertium: 3 case reports.
AB  - Clostridium tertium is infrequently isolated from blood in patients with
      underlying diseases. Laboratory diagnosis is often delayed because Clostridium
      tertium is aerotolerant and resistant to metronidazole. Clinically it is a
      problem because it is commonly resistant to metronidazole, clindamycin and
      cephalosporins. We present 3 cases illustrating these characteristics.

PMID- 15849059
TI  - Salmonella diskitis in a 2-year old immunocompetent child.
AB  - Spine infections are uncommon in paediatrics and are generally caused by
      Staphylococcus aureus. Salmonella spp. are a rare cause of spine infections,
      usually affecting children with sickle-cell anaemia. We present a case of group
      C1 Salmonella diskitis in a previously healty 2-y-old child, and review the
      relevant literature.

PMID- 15849060
TI  - Septic arthritis due to Mycobacterium szulgai in a patient with human
      immunodeficiency virus: case report.
AB  - Mycobacterium szulgai is a rare human pathogen that mainly causes pulmonary
      diseases. We report the first case of M. szulgai causing septic arthritis in a
      patient with human immunodeficiency virus. A culture from the joint aspiration
      was needed to isolate and identify this organism. The patient was treated
      successfully with ciprofloxacin, clarithromycin, and ethambutol.

PMID- 15849061
TI  - Fusarium osteomyelitis: case report and review of the literature.
AB  - We present a case of Fusarium osteomyelitis attributed to innocuous trauma in a
      patient with significant peripheral vascular disease and diabetes mellitus type
      2. Fusarium species have been reported to cause an increasing number of
      infections, particularly in severely immunocompromized patients. Colonization of
      normal skin has also been reported. To the best of the author's knowledge, there
      are 5 cases of Fusarium osteomyelitis described in English-language literature.
      There is also a report with little detail of Fusarium infection involving bone in
      3 patients with hematologic malignancy. We tabulated the pertinent facts of the 5
      detailed cases and compared them to ours. Early diagnosis requires some suspicion
      of invasive fungal infection. Tissue culture and pathologic examination are
      necessary for definitive diagnosis and to distinguish infection from
      colonization. Therapy includes antifungal drugs and aggressive surgical
      debridement, and even when these modalities are readily implemented the outcome
      may not be optimal because of the angioinvasive character of the organism.

PMID- 15849062
TI  - Development of a competitive immunoassay for the determination of N-(2
      hydroxyethyl)valine adducts in human haemoglobin and its application in
      biological monitoring.
AB  - Ethylene oxide (EO) is an important industrial compound and a directly acting
      mutagen. Human exposure to it can be monitored by the determination of
      haemoglobin (Hb) adducts. An immunoassay that quantifies the N-terminal adduct N
      (2-hydroxyethyl)valine in whole blood was developed, and its potential usefulness
      as a tool for biologically monitoring occupational exposure demonstrated.
      Analytical reliability was confirmed in a comparative study with gas
      chromatography-mass spectrometry (range 0.040-589 nmol g(-1) Hb, correlation
      coefficient 0.98, n=10). The assay was configured as a competitive enzyme-linked
      immunosorbent assay to facilitate the rapid throughput of samples. The assay uses
      a whole blood matrix and has a working range of 10-10000 pmol N-(2
      hydroxyethyl)valine g(-1) hB. The assay does not appear to be affected by
      structurally similar metabolites and has been used to determine adducts in human
      blood samples. The first results from potentially exposed workers indicate the
      assay might be a powerful tool for the routine occupational biomonitoring of EO
      exposure.

PMID- 15849063
TI  - Chromosome aberration and lipid peroxidation in chromium-exposed workers.
AB  - Chromosome aberration frequency and lipid peroxidation levels were analyzed to
      investigate their efficacy as biological markers for monitoring the genotoxicity
      and oxidative damage in Korean chromium (Cr)-exposed workers. Fifty-one Cr
      exposed workers and 31 age-matched controls in ten chrome-plating plants were
      sampled. The Cr level was measured in the workers' blood and urine, and in the
      ambient air at the workplaces. The conventional Giemsa staining method and
      fluorescence in situ hybridization (FISH) technique were used for chromosome
      aberration analysis. Spectrum green whole chromosome paint specific for
      chromosome 4 was used in the FISH procedure. As for lipid peroxidation,
      malondialdehyde (MDA) was measured in the blood plasma as thiobarbituric acid
      reactive substances (TBARS). The blood Cr concentration was statistically
      correlated with both the frequency of chromatid exchange and the total frequency
      of chromosome/chromatid breaks and exchanges, as detected by the Giemsa staining.
      Meanwhile, the frequency of translocation, as detected by the FISH technique, was
      significantly higher in the Cr-exposed workers than in the controls and it
      correlated with the blood Cr concentration. Although the concentration of MDA,
      the metabolite of lipid peroxidation, in the exposed workers was higher than that
      of the controls, no statistically significant correlation between the MDA level
      and the blood or urine Cr levels was observed. Accordingly, the genotoxicity and
      oxidative damage (plasma lipid peroxidation) in the Korean Cr-exposed workers
      were consequential at quite low exposure levels, plus chromosome rearrangement,
      especially translocation, was clearly evident as a biological response marker for
      Cr exposure based on a significant positive correlation between the
      translocations detected by FISH and the Cr in the blood.

PMID- 15849064
TI  - Evaluation of chromosomal damage by flow cytometry in turbot (Scophthalmus
      maximus L.) exposed to fuel oil.
AB  - Flatfishes, turbots (Scophthalmus maximus), were injected intraperitoneally with
      two doses of fuel oil number 2. Biliary metabolites were evaluated by fixed
      fluorescence to verify the efficiency of intoxication. Ethoxyresorufin-O
      deethylase (EROD) activity was compared with chromosomal damage measured by flow
      cytometry. The analysis of biliary metabolites showed a good dose-response
      relation and constitutes a clear reference for the subsequent measurements.
      Comparing flow cytometry and EROD results, a shorter delay of response for EROD
      activity was obtained, but chromosomal damage was significant only after one
      week. The persistence of the EROD response was shorter, while the genotoxic
      signal still persisted after one month. The measurement of chromosomal damage
      allowed a good differentiation between the two tested doses. In the case of EROD
      activity, the results were less clear. The results suggest that within a few
      weeks after exposure to fuel oil number 2, the measurements of chromosomal damage
      by flow cytometry can be used to detect a dose-dependent genotoxic response in
      fish.

PMID- 15849065
TI  - Identification of transcriptional biomarkers induced by SERMS in human
      endometrial cells using multivariate analysis of DNA microarrays.
AB  - Functional genomic tools such as DNA microarrays are having a major impact on the
      drug-discovery process. Potentially, compounds with toxic responses can be
      identified and removed at a relatively early stage in the drug-development
      process before tests on animals or humans, solely on the gene expression profiles
      produced in cell culture. The study examined the expression profiles of primary
      cultured human endometrial cells treated with 17beta-oestradiol and the SERMs
      (selective oestrogen receptor modulators) tamoxifen and raloxifene. Primary
      cultures from three individuals were split into glandular epithelial cells and
      stromal cell types. Principal components and partial least-squares-discriminate
      analyses were employed to examine the transcript profile as a whole, identifying
      genes responsible for patient separation and those that might have an important
      role in tamoxifen-associated carcinogenesis. Using multivariate data analysis,
      transcriptional responses were identified in epithelial cells but not in stromal
      cells for the three SERMs examined. However, it was demonstrated that a major
      problem associated with using primary cultures derived from human patients is the
      large transcriptional differences that might exist between the different
      cultures.

PMID- 15849066
TI  - Systemic markers of the redox balance in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is highly prevalent and its
      pathogenesis is still not completely clarified. Clinically stable patients (n=21)
      and healthy subjects (n=24) were studied for blood markers of oxidative injury
      and antioxidant status. The plasma concentration of protein carbonyls was
      significantly increased in COPD patients, both ex-smokers (0.76 +/- 0.28 nmol mg(
      1)) and smokers (0.99 +/- 020 nmol mg(-1)) versus controls (0.49 +/- 0.14 nmol
      mg(-1)) . The concentration of total thiols was slightly enhanced in plasma of
      the COPD patients (ex-smokers 492 +/- 23 micromol 1(-1) and smokers 505 +/- 36
      micromol 1(-1) versus controls 450 +/- 67 micromol 1(-1); p < 0.05). The activity
      of the antioxidant enzyme superoxide dismutase was increased in erythrocytes
      (activity in U g(-1) haemoglobin; ex-smokers 4460 +/- 763 and smokers 4114+/-
      1060 versus 3015 +/- 851 in controls; p > 0.01), while glutathione peroxidase
      activity was decreased in total blood (activity in U g(-1) haemoglobin: ex
      smokers 27 +/- 9 and smokers 23 +/- 9 versus 47 +/- 25; p < 0.01). Lower levels
      of selenium in plasma were also found for COPD patients (concentration in mg 1(
      1): ex-smokers 0.030 +/- 0.019 and smokers 0.032 +/- 0.024 versus 0.058 +/- 0.023
      in controls; p < 0.01), being more evident in those with very low levels of
      arterial oxygen pressure. In addition, the levels of potassium and rubidium were
      increased in blood cells of the patient group. All these changes might reflect
      oxidant damage and an altered electrolytic homeostasis, and can be interpreted as
      markers of COPD rather than as indicators of smoking habits.

PMID- 15849067
TI  - Genetic polymorphisms of cytokine genes and risk for trichloroethylene-induced
      severe generalized dermatitis: a case-control study.
AB  - Trichloroethylene (TCE)-induced severe generalized dermatitis (SGD) is considered
      to be a contact allergic disease and is dependent on a cell-mediated immune
      response. Little is known about its pathogenesis. Several lines of evidence
      suggest that tumour necrosis factor (TNF) and interleukin 4 (IL-4) are involved
      in the immunological and inflammatory reactions. To investigate the relation
      between polymorphisms of TNF and the IL-4 gene and the risk of TCE-induced SGD, a
      case-control study was conducted consisting of 111 patients diagnosed with SGD
      and 152 TCE-exposed workers without SGD. Polymerase chain reaction-restriction
      fragment length polymorphism was used to detect the polymorphisms of TNF-alpha (G
      238A, G-308A), TNF-beta (intron 1) and IL-4 (C-590T). Logistic regression was
      applied to calculate the odds ratios (OR) and 95% confidence intervals. The
      results reveal that the frequency of TNF alpha-308 wild allele in cases was
      significantly higher than that in control subjects (p=0.049). Individuals with a
      heterozygous genotype of TNF alpha-308 were associated with the decreased risk of
      TCE-induced SGD relative to the homozygous genotype (OR=0.398, 95% CI=0.164
      0.967). No significant differences in the allele and genotype frequencies could
      be demonstrated at any other polymorphic loci among both groups. The finding of a
      possible contribution of a TNF-alpha genetic polymorphism is a primary result
      because the pathogenesis of TCE-induced SGD is complex and likely to involve the
      interaction of a number of genes. A further study should be conducted to
      illustrate the influence of a link between certain relevant alleles in the
      assessment of genetic susceptibility

PMID- 15849068
TI  - Vitamin K in combination with other biochemical markers to diagnose osteoporosis.
AB  - The significance of a multiparametric classification approach of vitamin K is
      analysed to differentiate premenopausal (CTRL), postmenopausal non-osteoporotic
      (nOSP) and osteoporotic (OSP) women. Data records of women between 28 and 74
      years of age were used for evaluation. Bone mineral density was determined by
      quantitative computed tomography of the lumbar spine using the T-score to
      diagnose osteoporosis. Vitamin K and biochemical markers of bone formation and
      resorption--alkaline phosphatase (AP), bone alkaline phosphatase (bAP),
      osteocalcin (OC), undercarboxylated osteocalcin (ucOC), procollagen type I
      carboxyterminal propeptide (PICP), pyridinoline (PYD), deoxypyridinoline (DPD), N
      terminal cross-linked telopeptide of type I collagen (NTx) and bone sialo protein
      (BSP)--were analysed in all women on days 1 and 42. Vitamin K was significantly
      lower in the OSP group versus nOSP and CTRL. The odds ratio results revealed the
      following: vitamin K, 16.7; PYD, 7.5; NTx, 6.0; DPD, 2.7; and ucOC, 2.7. Vitamin
      K represented a sensitivity rate of 64% and a specificity rate of 82%. In the
      receiver operating curve analysis, vitamin K reached the highest area under curve
      (AUC) score. The combination of vitamin K and AP, bAP and PYD resulted in
      increased AUC scores (>0.9). The parameter combination of vitamin K/PYD and
      vitamin K/bAP demonstrated a sensitivity rate of 75-88%, with a specificity rate
      of more than 82%. The data suggests that a combination of vitamin K with other
      biochemical bone indices might be a useful tool for assessing bone metabolism,
      especially in metabolic bone diseases such as osteoporosis.

PMID- 15849095
TI  - Improving the quality of nursing homes. Introduction to a symposium on the role
      of regulation.

PMID- 15849097
TI  - The nursing home quality initiative. Shift in policy, shift in paradigm.

PMID- 15849096
TI  - LTC regulation and enforcement. An overview from the perspective of residents and
      their families.

PMID- 15849098
TI  - Driving improvement in long-term care. Enforcement and quality initiatives.

PMID- 15849099
TI  - The American Geri-wars. Moving beyond our encampments.

PMID- 15849100
TI  - Discharge planning in acute care and long-term facilities.

PMID- 15849101
TI  - Protecting the objectivity, fairness, and integrity of neuropsychological
      evaluations in litigation. A privilege second to none?

PMID- 15849155
TI  - Primary progressive aphasia: a review.
AB  - This review summarizes clinical and imaging features associated with primary
      progressive aphasia (PPA). We investigate the hypothesis that these patients can
      be divided into subgroups of progressive non-fluent aphasia (PNFA) and semantic
      dementia (SD), based on their linguistic profiles and related imaging studies,
      and examine whether each of these major subgroups can be further subdivided. We
      focus on several critical features within each progressive aphasic subgroup. In
      PNFA, we examine agrammatism, phonologic disorder, and impaired verb processing
      to determine whether this syndrome is related to a modality-specific impairment
      in word formation and articulation, or a conceptual deficit that interferes with
      grammatical processing. In SD, we examine impaired semantic memory, limited
      remote memory, and anomia to assess whether this syndrome is due to a modality
      neutral interruption of semantic memory, or the degradation of various material
      specific representations of object features and words. We conclude that there is
      sufficiently consistent and converging evidence from clinical and imaging studies
      to support the claim that PNFA and SD are distinct subgroups of PPA. However,
      there does not appear to be sufficient evidence at this point to support further
      discrimination within these progressive aphasic subgroups. Testing hypotheses
      about finer-grained syndromes such as progressive dysarthria or progressive
      anomia has important consequences for improving our understanding of language
      organization and the neural basis for language.

PMID- 15849156
TI  - Disordered knowledge of action order in action disorganisation syndrome.
AB  - We report data on stored knowledge of everyday tasks in a patient, FK, with
      'action disorganisation syndrome'. In section 1, we analysed his explicit
      knowledge of the component actions, and their temporal order. FK showed generally
      impaired knowledge of everyday tasks relative to controls, and, when knowledge of
      the temporal order of the actions was probed, he showed particular impairments
      for the actions making up the final steps in tasks. In section 2 we assessed FK's
      implicit knowledge of the tasks, by evaluating how knowledge of the tasks
      influenced his ability to act out sets of instructions. We demonstrate that FK
      had some implicit knowledge of the tasks, but also, when actions had to be
      performed in the order as instructed, there was better knowledge of order for
      actions performed early rather than late in the task. We suggest that disordered
      task schema contributed to FK's deficits, with impairments on 'end' actions being
      vulnerable when task order was important for performance.

PMID- 15849157
TI  - Just thinking about targets can aggravate neglect on cancellation tests.
AB  - While many studies investigate how the visual features of targets influence
      cancellation performance in neglect, few, if any, even consider that thought
      processes, such as the use of an algorithm to identify targets, might similarly
      aggravate neglect. This single-case study of a patient with chronic neglect
      compared cancellation performance after manipulating (1) ease of visual target
      identification, (2) the use of an algorithm to identify targets, and (3) the
      material-specific nature of target cancellation. Neglect severity was defined by
      the number and location of target omissions. While each manipulation had a
      differential impact on neglect severity, the novel and interesting finding
      occurred during the second condition, when a math algorithm was used to identify
      targets. In this condition, target omissions increased relative to other tests
      and target cancellations were confined to the right half of the page. This is the
      first report, to our knowledge, that neglect on cancellation tests can be
      aggravated by an internal thought process, a math algorithm, as opposed to
      external manipulations of visual stimuli and procedural characteristics of
      cancellation tests. An important characteristic of the algorithm used in this
      study is that it appeared to activate the intact left cerebral hemisphere.

PMID- 15849158
TI  - Sub-types of deep dyslexia: a case study of central deep dyslexia.
AB  - A case study is reported of a female patient (JAH), who following a left middle
      cerebral artery infarct, presented with the cardinal symptoms of deep dyslexia
      and deep dysphasia (semantic errors when reading and repeating words aloud,
      respectively). Detailed assessment revealed impaired performance across
      modalities for many tasks, but particularly those tasks that depend on an intact
      store of semantic knowledge. Her acquired dyslexia is best characterised as deep
      dyslexia of a central sub-type.

PMID- 15849159
TI  - Cortical sensory loss in a patient with posterior cortical atrophy: a case
      report.
AB  - Patients with posterior cortical atrophy (PCA) who present with initial symptoms
      of higher visual function deficits eventually develop alexia, aphasia, and
      components of Balint's syndrome or Gerstmann's syndrome. Recently, pathological
      findings were reported for these patients that are generally suggestive of
      Alzheimer's disease even though Creutzfeldt-Jakob disease (CJD) was presumed as
      an alternative cause of some autopsy-diagnosed PCA cases. Here, we report a case
      with a four-year progression of cognitive and higher visual function
      deterioration, and with features not described in previously reported PCA cases
      (i.e., a distinct sensory complaint and early frontal lobe involvement). To
      summarize, this case belongs to perceptual-motor syndrome of asymmetric cortical
      degeneration and the underlying neuropathology is more suggestive of Alzheimer's
      disease than of Creutzfeldt-Jakob disease.

PMID- 15849160
TI  - Disorganised memory after right dorsolateral prefrontal damage.
AB  - Neurophysiological and functional brain imaging studies suggest the importance of
      dorsolateral area 9/46 for modality-independent working memory. However, the
      behavioural manifestations following isolated damage to this area have not been
      clearly outlined. Here, we describe the dramatic derangement of pragmatic memory
      after circumscribed lesion of the right area 9/46. A 52 year-old woman had
      suffered a traumatic brain injury 13 years ago and sought help for what she
      thought was a severe memory disorder. She regularly missed appointments and had
      gradually lost all her friends. She had tried different strategies to compensate
      for her memory problem, such as writing notes on her wrist or using electronic
      organizers. Intelligence, attention, verbal long-term memory, and executive
      functions were normal. Furthermore, experimental exploration demonstrated intact
      time estimation, attribution of memories to ongoing reality, and anticipation of
      outcomes. However, she failed to rehearse and manipulate information in working
      memory (n-back task), confirming the findings of functional imaging studies that
      the mid-dorsolateral prefrontal cortex is involved in mental manipulation of
      information. This case exemplifies that an isolated lesion of the right area 9/46
      may induce severe failure to schedule actions and memory retrieval, a disorder
      leading to severely disorganised behaviour and disability.

PMID- 15849161
TI  - Children with autism adapt normally during a catching task requiring the
      cerebellum.
AB  - The cerebellum, which has been found to be abnormal in histopathological studies
      of autism, is important for motor adaptation. We studied controls and children
      with high functioning autism (HFA) performing a catching adaptation test that is
      known to be impaired following cerebellar damage. Results showed no differences
      in adaptation rates or after-effects for HFA subjects versus controls. The
      findings indicate normal motor adaptation in HFA, suggesting normal or
      compensated cerebellar function for this task.

PMID- 15849162
TI  - The purpose of lexical/sublexical interaction during spelling: further evidence
      from dysgraphia and articulatory suppression.
AB  - We investigated how the lexical and sublexical processes interact in spelling
      using an articulatory suppression task to disrupt the sublexical process in a
      dysgraphic patient (JDO). Using a similar task, Folk et al. (2002) found evidence
      that the sublexical process interacts with the lexical process by strengthening a
      target word's graphemes. We replicated the findings of Folk et al. in a patient
      with a more severe deficit to the lexical process. We compared the error patterns
      produced under normal spelling conditions versus spelling during articulatory
      suppression and found an increase in lexical substitution errors ("thaw"-->T-H-O
      U-G-H) under articulatory suppression. These findings indicate that by
      strengthening a target word's graphemes, the sublexical process helps to create
      an advantage for a target word over form-related word neighbours that compete
      with it for output.

PMID- 15849163
TI  - Reappraising contemporary theories of subcortical participation in language:
      proposing an interhemispheric regulatory function for the subthalamic nucleus
      (STN) in the mediation of high-level linguistic processes.
AB  - Apropos the basal ganglia, the dominant striatum and globus pallidus internus
      (GPi) have been hypothesised to represent integral components of subcortical
      language circuitry. Working subcortical language theories, however, have failed
      thus far to consider a role for the STN in the mediation of linguistic processes,
      a structure recently defined as the driving force of basal ganglia output. The
      aim of this research was to investigate the impact of surgically induced
      functional inhibition of the STN upon linguistic abilities, within the context of
      established models of basal ganglia participation in language. Two males with
      surgically induced 'lesions' of the dominant and non-dominant dorsolateral STN,
      aimed at relieving Parkinsonian motor symptoms, served as experimental subjects.
      General and high-level language profiles were compiled for each subject up to 1
      month prior to and 3 months following neurosurgery, within the drug-on state
      (i.e., when optimally medicated). Comparable post-operative alterations in
      linguistic performance were observed subsequent to surgically induced functional
      inhibition of the left and right STN. More specifically, higher proportions of
      reliable decline as opposed to improvement in post-operative performance were
      demonstrated by both subjects on complex language tasks, hypothesised to entail
      the interplay of cognitive-linguistic processes. The outcomes of the current
      research challenge unilateralised models of functional basal ganglia organisation
      with the proposal of a potential interhemispheric regulatory function for the STN
      in the mediation of high-level linguistic processes.

PMID- 15849164
TI  - Heterogeneity is a fact of category-specific semantic deficits. so? comments on
      Rosazza, Imbornone, Zorzi, Farina, Chiavari, And Cappa (2003).
AB  - The Sensory/Functional Theory, until recently the received explanation of
      category-specific semantic deficits, has been shown to be at variance with
      various facts that have emerged about the nature of these deficits. In this
      context, Rosazza, Imbornone, Zorzi, Farina, Chiavari, and Cappa (2003: The
      Heterogeneity of Category-Specific Semantic Disorders: Evidence from a New Case.
      Neurocase, 9, 189-202.) report the case study of a patient, MA, with a purported
      category-specific semantic deficit for living things compared to nonliving
      things, and an associated modality-specific impairment that differentially
      affected visual/perceptual compared to functional/associative knowledge. While
      acknowledging that the Sensory/Functional Theory cannot account for the existence
      of category-specific semantic deficits, Rosazza and colleagues (2003) contend
      that "...the presence of a more severe loss of specific visual rather than
      functional knowledge could support an interpretation according to the
      Sensory/Functional Theory" [sic] (p. 200). Our comments are divided into two
      parts. First, we point out that there is an asymmetry between evidence and
      theory: if there is clear evidence that "disconfirms" a given theory, evidence
      that is consistent with the theory cannot be argued to support the theory.
      Second, we argue that the performance profile of MA could potentially be relevant
      to other interpretations of category-specific deficits but that theoretical
      interpretations of the performance profile of patient MA are undermined by a lack
      of methodological rigor, as well as the generally weak data associated with the
      case.

PMID- 15849167
TI  - Methods for expansion of human embryonic stem cells.
AB  - The manipulation of human embryonic stem cells (hESCs) requires refined skills.
      Here we introduce both mechanical and enzymatic transfer methods for hESCs
      depending on experimental purpose. We use the mechanical transfer method for
      maintenance of hESC lines. Although the method is laborious and time-consuming,
      the technique permits efficient transfer of undifferentiated hESCs and results in
      similar clump sizes. We implement the enzymatic transfer method when we need the
      bulk production of cells for various experiments. The enzyme-treated expansion
      rapidly produces greater amounts of hESCs within a limited time frame. However,
      the cell clumps vary in size, and there is a probability that both the
      differentiated and undifferentiated cells will be transferred. In cases in which
      there are differentiated colonies, the combination of two methods allows mass
      production of hESCs by excluding differentiated colonies from passage by manual
      selection before enzyme treatment.

PMID- 15849166
TI  - Ghrelin treatment reverses the reduction in weight gain and body fat in
      gastrectomised mice.
AB  - BACKGROUND AND AIMS: The gastric hormone ghrelin has been reported to stimulate
      food intake, increase weight gain, and cause obesity but its precise
      physiological role remains unclear. We investigated the long term effects of
      gastrectomy evoked ghrelin deficiency and of daily ghrelin injections on daily
      food intake, body weight, fat mass, lean body mass, and bone mass in mice.
      METHODS: Ghrelin was given by subcutaneous injections (12 nmol/mouse once daily)
      for eight weeks to young female mice subjected to gastrectomy or sham operation
      one week previously. RESULTS: Gastrectomy reduced plasma concentrations of total
      ghrelin (octanoylated and des-octanoylated) and active (octanoylated) ghrelin by
      approximately 80%. Immediately after injection of ghrelin, the plasma
      concentration was supraphysiological and was still elevated 16 hours later. Daily
      food intake was not affected by either gastrectomy or ghrelin treatment. The
      effect of ghrelin on meal initiation was not studied. At the end point of the
      study, mean body weight was 15% lower in gastrectomised mice than in sham
      operated mice (p<0.001); daily ghrelin injections for eight weeks partially
      prevented this weight loss. In sham operated mice, ghrelin had no effect on body
      weight. The weight of fat was reduced in gastrectomised mice (-30%; p<0.01). This
      effect was reversed by ghrelin, enhancing the weight of fat in sham operated mice
      also (+20%; p<0.05). Gastrectomy reduced lean body mass (-10%; p<0.01) and bone
      mass (-20%; p<0.001) compared with sham operated mice. Ghrelin replacement
      prevented the gastrectomy induced decrease in lean body mass but did not affect
      bone. In sham operated mice, ghrelin affected neither of these two parameters.
      CONCLUSIONS: Ghrelin replacement partially reversed the gastrectomy induced
      reduction in body weight, lean body mass, and body fat but not in bone mass. In
      sham operated mice, ghrelin only increased fat mass. Our results suggest that
      ghrelin is mainly concerned with the control of fat metabolism and that ghrelin
      replacement therapy may alleviate the weight loss associated with gastrectomy.

PMID- 15849168
TI  - Two different roles of purified CD45+c-Kit+Sca-1+Lin- cells after transplantation
      in muscles.
AB  - Recent studies have indicated that bone marrow cells can regenerate damaged
      muscles and that they can adopt phenotypes of other cells by cell fusion. Our
      direct visualization system gave evidence of massive muscle regeneration by green
      fluorescent protein (GFP)-labeled CD45+c-Kit+Sca-1+Lin- cells (KSL cells), and we
      investigated the role of KSL cells in muscle regeneration after transplantation
      with or without lethal irradiation. In the early phase, GFP signals were clearly
      observed in all the muscles of only irradiated mice. Transverse cryostat sections
      showed GFP+myosin+ muscle fibers, along with numerous GFP+ hematopoietic cells in
      damaged muscle. These phenomena were temporary, and GFP signals had dramatically
      reduced 30 days after transplantation. After 6 months, GFP+ fibers could hardly
      be detected, but GFP+c-Met+ mononuclear cells were located beneath the basal
      lamina where satellite cells usually exist in both conditioned mice.
      Immunostaining of isolated single fibers revealed GFP+PAX7+, GFP+MyoD+, and
      GFP+Myf5+ satellite-like cells on the fibers. Single-fiber cultures from these
      mice showed proliferation of GFP+ fibers. These results indicate two different
      roles of KSL cells: one leading to regeneration of damaged muscles in the early
      phase and the other to conversion into satellite cells in the late phase.

PMID- 15849169
TI  - Identification and hematopoietic potential of CD45- clonal cells with very
      immature phenotype (CD45-CD34-CD38-Lin-) in patients with myelodysplastic
      syndromes.
AB  - CD45 is a hematopoietic lineage-restricted antigen that is expressed on all
      hematopoietic cells except for some mature cell types. Cells expressing CD45 and
      CD34 but lacking CD38 and lineage antigens (CD45+CD34+CD38-Lin- cells) are well
      documented hematopoietic stem cells (HSCs), and CD45+CD34-CD38-Lin- cells are
      probably less mature HSCs. In myelodysplastic syndromes (MDS), the malignant
      transformation site is a matter of debate, and CD45+CD34+CD38-Lin- HSCs were
      recently reported to be clonal. In the study reported here, we detected CD45-CD34
      CD38-Lin- cells in the peripheral blood and bone marrow of patients with MDS and
      isolated them by successive application of density centrifugation, magnetic cell
      sorting, and fluorescence-activated cell sorting. Fluorescence in situ
      hybridization showed that CD45-CD34-CD38-Lin- cells had the same chromosomal
      aberration as the myeloblasts. In addition to CD45- and CD34-, they lacked CD117
      and CD133 expression. Generally, MDS cells have extremely reduced hematopoietic
      potential compared with normal hematopoietic cells, but we documented the
      following in some patients. Freshly isolated CD45-CD34-CD38-Lin- cells did not
      form any hematopoietic colonies but had long-term culture-initiating cell
      activity. When cocultured with stroma cells, CD45-CD34-CD38-Lin- cells showed
      only weak potential for proliferation and differentiation, yet they
      differentiated into CD34+ cells and then mature myeloid cells. This newly
      identified cell population represents the most immature immunophenotype so far
      identified in the hematopoietic lineage and is involved in the malignant clone in
      MDS.

PMID- 15849170
TI  - Detection of aberrant gene expression in CD34+ hematopoietic stem cells from
      patients with agnogenic myeloid metaplasia using oligonucleotide microarrays.
AB  - Agnogenic myeloid metaplasia (AMM) is a clonal stem cell disorder that leads to
      ineffective hematopoiesis, bone marrow fibrosis, and extramedullary
      hematopoiesis. The molecular mechanisms underlying the development of this
      syndrome are currently unknown. Therefore, the aim of this study was to
      characterize aberrant gene expression in CD34+ hematopoietic stem cells from
      patients with AMM. We used oligonucleotide microarrays to analyze gene expression
      profiles in CD34+ hematopoietic stem cells from patients with AMM compared with
      expression in CD34+ cells from healthy individuals. We identified 95 highly
      differentially expressed genes (48 upregulated and 47 down-regulated) that are
      potentially involved in regulating abnormal hematopoietic proliferation and
      differentiation and confirmed many of them by quantitative polymerase chain
      reaction. Using class membership prediction analysis, we identified 75 genes
      whose expression profiles can accurately differentiate AMM samples from the
      controls. Using these 75 genes, we were able to discriminate patients with AMM
      from the controls by hierarchical clustering (Spearman's confidence correlation).
      The predictive power of these genes was verified by applying the algorithm to an
      unknown test set containing expression data from eight additional CD34+ samples
      (four AMM, four control). Our results indicate that a subset of genes may be used
      to differentiate patients with AMM from healthy individuals. Furthermore, we
      identify 95 genes whose aberrant expression may be involved in AMM.

PMID- 15849171
TI  - Donor marker infidelity in transgenic hematopoietic stem cells.
AB  - Transgenic marking approaches are increasingly used to evaluate the developmental
      potential of stem cells. However, cell fate mapping studies using different
      transgenic marking systems have produced conflicting results. These disparate
      findings may be due in part to the infidelity of donor marker gene expression.
      Analysis of hematopoietic stem cells (c-Kit+, Sca-1+, lineage marker- [KSL]) from
      a transgenic mouse (1Osb) engineered to ubiquitously express the enhanced green
      fluorescent protein (EGFP) reveals two distinct populations. Forty percent of KSL
      cells demonstrate intermediate levels of EGFP fluorescence and differentiate into
      subpopulations of B cells, T cells, and myeloid cells that do not express EGFP.
      By contrast, progeny of the remaining 60% of KSL cells are almost exclusively
      EGFP bright. Long-term multilineage hematopoietic reconstitution and serial
      transplantation experiments show that these differences in EGFP are a property of
      self-renewing stem cells. Furthermore, both the transgene integration site and
      the activation status of a cell are important determinants of EGFP expression.
      These results indicate that a combination of donor cell markers is required to
      reliably track the full differentiation potential of transgenic stem cells.

PMID- 15849172
TI  - Activation of stem-cell specific genes by HOXA9 and HOXA10 homeodomain proteins
      in CD34+ human cord blood cells.
AB  - There is growing evidence for a role of HOX homeodomain proteins in normal
      hematopoiesis. Several HOX genes, including HOXA9 and HOXA10, are expressed in
      primitive hematopoietic cells, implying a role in early hematopoietic
      differentiation. To identify potential target genes of these two closely related
      transcription factors, human CD34+ umbilical cord blood cells were transduced
      with vectors expressing either HOXA9 or HOXA10 and analyzed with cDNA micro
      arrays. Statistical analysis using significance analysis of microarrays revealed
      a common signature of several hundred genes, demonstrating that the
      transcriptomes of HOXA9 and HOXA10 largely overlap in this cellular context.
      Seven genes that were upregulated by both HOX proteins were validated by real
      time reverse transcription polymerase chain reaction. HOXA9 and HOXA10 showed
      positive regulation of genes in the Wnt pathway, including Wnt10B and two Wnt
      receptors Frizzled 1 and Frizzled 5, an important pathway for hematopoietic stem
      cell (HSC) self-renewal. Other validated genes included v-ets-related gene (ERG),
      Iroquois 3 (IRX3), aldehyde dehydrogenase 1 (ALDH1), and very long-chain acyl-CoA
      synthetase homolog 1 (VLCS-H1). GenMAPP (Gene Micro Array Pathway Profiler)
      analysis indicated that HOXA10 repressed expression of several genes involved in
      heme biosynthesis and three globin genes, indicating a general suppression of
      erythroid differentiation. A number of genes regulated by HOXA9 and HOXA10 are
      expressed in normal HSC populations.

PMID- 15849173
TI  - Inducing embryonic stem cells to differentiate into pancreatic beta cells by a
      novel three-step approach with activin A and all-trans retinoic acid.
AB  - Experimental induction of embryonic stem cells (ESCs) to become pancreatic beta
      cells can potentially provide ample resource for cell transplantation therapy of
      type I diabetes mellitus. Most of the previously reported induction strategies
      were long and complicated, and some required genetic manipulation. Moreover, it
      has been indicated that the insulin staining of ESC progeny was insulin uptake
      from the culture medium. Here we show that a simple three-step experimental
      approach based on the combination induction by activin A, all-trans retinoic
      acid, and other mature factors is able to induce murine ESCs to differentiate
      into insulin-producing cells in 2 weeks, and that insulin release of these
      induced cells is regulated by the glucose concentration. Our insulin-enhanced
      green fluorescent green protein reporter system excludes the possibility of
      insulin uptake. Transplantation of these ESC-derived insulin-positive cells can
      normalize blood glucose levels and rescue the survival of streptozocin-induced
      diabetic mice. The findings reported here offer a novel in vitro model to study
      the differentiation mechanism of pancreatic beta cells and a potential source of
      insulin-producing cells for transplantation therapy of type I diabetes mellitus.

PMID- 15849174
TI  - Correlation of murine embryonic stem cell gene expression profiles with
      functional measures of pluripotency.
AB  - Global gene expression profiling was performed on murine embryonic stem cells
      (ESCs) induced to differentiate by removal of leukemia inhibitory factor (LIF) to
      identify genes whose change in expression correlates with loss of pluripotency.
      To identify appropriate time points for the gene expression analysis, the
      dynamics of loss of pluripotency were investigated using three functional assays:
      chimeric mouse formation, embryoid body generation, and colony-forming ability. A
      rapid loss of pluripotency was detected within 24 hours, with very low residual
      activity in all assays by 72 hours. Gene expression profiles of undifferentiated
      ESCs and ESCs cultured for 18 and 72 hours in the absence of LIF were determined
      using the Affymetrix GeneChip U74v2. In total, 473 genes were identified as
      significantly differentially expressed, with approximately one third having
      unknown biological function. Among the 275 genes whose expression decreased with
      ESC differentiation were several factors previously identified as important for,
      or markers of, ESC pluripotency, including Stat3, Rex1, Sox2, Gbx2, and Bmp4. A
      significant number of the decreased genes also overlap with previously published
      mouse and human ESC data. Furthermore, several membrane proteins were among the
      48 decreased genes correlating most closely with the functional assays, including
      the stem cell factor receptor c-Kit. Through identification of genes whose
      expression closely follows functional properties of ESCs during early
      differentiation, this study lays the foundation for further elucidating the
      molecular mechanisms regulating the maintenance of ESC pluripotency and
      facilitates the identification of more reliable molecular markers of the
      undifferentiated state.

PMID- 15849175
TI  - Cryopreservation does not affect proliferation and multipotency of murine neural
      precursor cells.
AB  - Stem cell research offers unique opportunities for developing new medical
      therapies for devastating diseases and a new way to explore fundamental questions
      of biology. Establishing an efficient freezing protocol for neural precursor
      cells (NPCs) is of great importance for advances in cell-based therapies. We used
      fluorescence-activated cell sorter-based cell death/survival analysis and Western
      blot analysis of proliferation markers (proliferating cell nuclear antigen) and
      prosurvival proteins (Bcl-2) to study the effect of a variety of cryoprotective
      agents on fetal mouse forebrain NPCs. Neurospheres frozen at -70 degrees C or in
      liquid nitrogen in a rate-controlled manner and thawed after 5 days retained
      viability of 60%-70% measured 24 hours after thawing. However, 1 week after
      thawing, viability dropped to 50%-60%. Using a clonogenic sphere formation assay,
      we showed that recovery rate of frozen NPCs was approximately 26% and did not
      significantly differ between dimethyl sulfoxide (DMSO)- and glycerol-supplemented
      samples. Application of the caspase inhibitor zVAD-fmk during freezing or in the
      first week after thawing resulted in protection of cryopreserved neurospheres
      after thawing but not during the freezing process, indicating that apoptosis
      limits recovery of NPCs. Cell survival was not reduced in cells that were
      enzymatically separated before cryopreservation. Optimal protection of NPCs was
      achieved when 10% DMSO alone or in a combination with 10% fetal calf serum (FCS)
      was used. However, 10% glycerol alone was equally effective. Using these
      protocols, NPCs retained their multipotency and differentiated into both glial
      (GFAP-positive) and neuronal (Tuj1-positive) cells. Percentage of Tuj1-positive
      cells in 5% and 10% DMSO, in 10% DMSO + 10% FCS, and in 10% glycerol remained at
      the same level as before freezing and varied from 5%-7%. We conclude that
      cryopreservation (up to 1 month at -70 degrees C and up to 1 year in liquid
      nitrogen) does not markedly alter the rate of proliferation and multipotency of
      murine neural precursor cells.

PMID- 15849176
TI  - Development of novel markers for the characterization of chicken primordial germ
      cells.
AB  - This study was undertaken to develop novel markers for chicken primordial germ
      cells (PGCs), which are of potentially enormous value in transgenic research.
      Gonadal cells collected from 5.5-day-old chicken embryos were cultured in a
      Dulbecco's minimal essential medium and the PGC colonies formed during the
      primary culture period were subcultured three times. Characterization of the PGCs
      with the candidate marker reagents was performed on the mixed cell population 2
      hours after seeding, after the primary culture period (day 10), and after the
      third passage (day 40). Mouse embryonic stem (ES) cells were used as controls.
      The cytochemical reagents investigated included periodic acid-Schiff (PAS) stain,
      antibodies to stage-specific embryonic antigens (SSEA-1, SSEA-3, and SSEA-4),
      antibody to epithelial membrane antigen (EMA)-1, antibodies to integrins alpha6
      and beta1, several lectins (Solanum tuberosum agglutinin [STA], Dolichos biflorus
      agglutinin [DBA], concanavalin A agglutinin [ConA], and wheat germ agglutinin
      [WGA]), and double staining with antibodies to SSEA-1, SSEA-3, SSEA-4, integrin
      alpha6, or integrin beta1 and then with the lectin STA. Densitometric
      quantification was used to identify PGC-specific markers. The results showed that
      chicken PGCs were stained selectively by PAS and by antibodies to SSEA-1, SSEA-3,
      SSEA-4, EMA-1, integrin alpha6, and integrin beta1. The control mouse ES cells
      reacted with PAS, anti-SSEA-1, and anti-EMA-1 antibodies, as well as with
      antibodies to integrins alpha6 and beta1, but not with antibodies to SSEA-3 and
      SSEA-4. Chicken PGCs reacted with the lectins STA and DBA, but mouse ES cells
      reacted with STA and WGA. The results of double staining of PGC colonies
      subcultured three times showed that the intensity of staining was not altered by
      concomitant use of the marker reagents. This study demonstrated that, in addition
      to PAS and antibodies to SSEA-1 and EMA-1, new specific markers of chicken PGCs
      are recognized by the lectins STA and DBA and by antibodies to SSEA-3 and SSEA-4
      and integrins alpha6 and beta1. Double staining using these newly developed
      markers might be the method of choice for rapid characterization of chicken PGCs.

PMID- 15849177
TI  - In vivo characterization of bone marrow-derived fibroblasts recruited into
      fibrotic lesions.
AB  - Fibroblasts, which are widely distributed and play a key part in tissue fibrosis,
      are phenotypically and functionally heterogeneous. Recent studies reported that
      bone marrow can be a source of tissue fibroblast. In the study reported here, we
      investigated in vivo characterization of bone marrow-derived fibroblasts
      recruited into various fibrotic lesions. Mice were engrafted with bone marrow
      isolated from transgenic mice expressing green fluorescent protein (GFP), and
      fibrotic lesions were induced by cancer implantation (skin), excisional wounding
      (skin), and bleomycin administration (lung). A small population of GFP+
      fibroblast was found even in nonfibrotic skin (8.7% +/- 4.6%) and lung (8.9% +/-
      2.5%). The proportion of GFP+ fibroblasts was significantly increased after
      cancer implantation(59.7% +/- 16.3%) and excisional wounding (32.2% +/- 4.8%),
      whereas it was not elevated after bleomycin administration (7.1% +/- 2.4%).
      Almost all GFP+ fibroblasts in fibrotic lesions expressed type I collagen,
      suggesting that bone marrow-derived fibroblasts would contribute to tissue
      fibrosis. GFP+ fibroblasts expressed CD45, Thy-1, and alpha-smooth muscle actin
      at various proportions. Our results suggested that bone marrow-derived
      fibroblasts expressed several fibroblastic markers in vivo and could be
      efficiently recruited into fibrotic lesions in response to injurious stimuli;
      however, the degree of recruitment frequency might depend on the tissue
      microenvironment.

PMID- 15849178
TI  - The Promises and Challenges of Regenerative Medicine, October 20-22, 2004, Kobe,
      Japan.
AB  - This report provides a brief summary of information presented at a workshop on
      regenerative medicine held in Kobe, Japan, on October 20-22, 2004. A major focus
      of the workshop was the identification and characterization of adult and
      embryonic stem cells, including approaches to manipulate these--in terms both of
      maintaining stemness and of driving differentiation toward a desired phenotype-
      and current developments toward their therapeutic use in regenerative medicine.

PMID- 15849179
TI  - The molecular perspective: l-asparaginase.

PMID- 15849180
TI  - The C-terminal (331-376) sequence of Escherichia coli DnaJ is essential for
      dimerization and chaperone activity: a small angle X-ray scattering study in
      solution.
AB  - DnaJ, an Escherichia coli Hsp40 protein composed of 376 amino acid residues, is a
      chaperone with thioldisulfide oxidoreductase activity. We present here for the
      first time a small angle x-ray scattering study of intact DnaJ and a truncated
      version, DnaJ (1-330), in solution. The molecular weight of DnaJ and DnaJ (1-330)
      determined by both small angle x-ray scattering and size-exclusion chromatography
      provide direct evidence that DnaJ is a homodimer and DnaJ (1-330) is a monomer.
      The restored models show that DnaJ is a distorted omega-shaped dimeric molecule
      with the C terminus of each subunit forming the central part of the omega,
      whereas DnaJ (1-330) exists as a monomer. This indicates that the deletion of the
      C-terminal 46 residues of DnaJ impairs the association sites, although it does
      not cause significant conformational changes. Biochemical studies reveal that
      DnaJ (1-330), while fully retaining its thiol-disulfide oxidoreductase activity,
      is structurally less stable, and its peptide binding capacity is severely
      impaired relative to that of the intact molecule. Together, our results reveal
      that the C-terminal (331-376) residues are directly involved in dimerization, and
      the dimeric structure of DnaJ is necessary for its chaperone activity but not
      required for the thiol-disulfide oxidoreductase activity.

PMID- 15849181
TI  - Recombinant severe acute respiratory syndrome (SARS) coronavirus nucleocapsid
      protein forms a dimer through its C-terminal domain.
AB  - The causative agent of severe acute respiratory syndrome (SARS) is the SARS
      associated coronavirus, SARS-CoV. The viral nucleocapsid (N) protein plays an
      essential role in viral RNA packaging. In this study, recombinant SARS-CoV N
      protein was shown to be dimeric by analytical ultracentrifugation, size exclusion
      chromatography coupled with light scattering, and chemical cross-linking. Dimeric
      N proteins self-associate into tetramers and higher molecular weight oligomers at
      high concentrations. The dimerization domain of N was mapped through studies of
      the oligomeric states of several truncated mutants. Although mutants consisting
      of residues 1-210 and 1-284 fold as monomers, constructs consisting of residues
      211-422 and 285-422 efficiently form dimers. When in excess, the truncated
      construct 285-422 inhibits the homodimerization of full-length N protein by
      forming a heterodimer with the full-length N protein. These results suggest that
      the N protein oligomerization involves the C-terminal residues 285-422, and this
      region is a good target for mutagenic studies to disrupt N protein self
      association and virion assembly.

PMID- 15849182
TI  - Annexin A2-S100A10 heterotetramer, a novel substrate of thioredoxin.
AB  - The binding of plasminogen activators and plasminogen to the cell surface results
      in the rapid generation of the serine protease plasmin. Plasmin is further
      degraded by an autoproteolytic reaction, resulting in the release of an
      angiostatin, A61 (Lys78-Lys468). Previously, we demonstrated that the annexin A2
      S100A10 heterotetramer (AIIt) stimulates the release of A61 from plasmin by
      promoting the autoproteolytic cleavage of the Lys468-Gly469 bond and reduction of
      the plasmin Cys462-Cys541 disulfide (Kwon, M., Caplan, J. F., Filipenko, N. R.,
      Choi, K. S., Fitzpatrick, S. L., Zhang, L., and Waisman, D. M. (2002) J. Biol.
      Chem. 277, 10903-10911). Mechanistically, it was unclear if AIIt promoted a
      conformational change in plasmin, resulting in contortion of the plasmin
      disulfide, or directly reduced the plasmin disulfide. In the present study, we
      show that AIIt thiols are oxidized during the reduction of plasmin disulfides,
      establishing that AIIt directly participates in the reduction reaction.
      Incubation of HT1080 cells with plasminogen resulted in the rapid loss of thiol
      specific labeling of AIIt by 3-(N-maleimidopropionyl)biocytin. The plasminogen
      dependent oxidation of AIIt could be attenuated by thioredoxin. Thioredoxin
      reductase catalyzed the transfer of electrons from NADPH to the oxidized
      thioredoxin, thus completing the flow of electrons from NADPH to AIIt. Therefore,
      we identify AIIt as a substrate of the thioredoxin system and propose a new model
      for the role of AIIt in the redox-dependent processing of plasminogen and
      generation of an angiostatin at the cell surface.

PMID- 15849183
TI  - High resolution structures of highly bulged viral epitopes bound to major
      histocompatibility complex class I. Implications for T-cell receptor engagement
      and T-cell immunodominance.
AB  - Although HLA class I alleles can bind epitopes up to 14 amino acids in length,
      little is known about the immunogenicity or the responding T-cell repertoire
      against such determinants. Here, we describe an HLA-B*3508-restricted cytotoxic T
      lymphocyte response to a 13-mer viral epitope (LPEPLPQGQLTAY). The rigid,
      centrally bulged epitope generated a biased T-cell response. Only the N-terminal
      face of the peptide bulge was critical for recognition by the dominant clonotype
      SB27. The SB27 public T-cell receptor (TcR) associated slowly onto the complex
      between the bulged peptide and the major histocompatibility complex, suggesting
      significant remodeling upon engagement. The broad antigen-binding cleft of HLA
      B*3508 represents a critical feature for engagement of the public TcR, as the
      narrower binding cleft of HLA-B*3501(LPEPLPQGQLTAY), which differs from HLA
      B*3508 by a single amino acid polymorphism (Arg156 --> Leu), interacted poorly
      with the dominant TcR. Biased TcR usage in this cytotoxic T lymphocyte response
      appears to reflect a dominant role of the prominent peptide x major
      histocompatibility complex class I surface.

PMID- 15849184
TI  - A functional dermatan sulfate epitope containing iduronate(2-O-sulfate)alpha1
      3GalNAc(6-O-sulfate) disaccharide in the mouse brain: demonstration using a novel
      monoclonal antibody raised against dermatan sulfate of ascidian Ascidia nigra.
AB  - Oversulfated chondroitin sulfate (CS), dermatan sulfate (DS), and CS/DS hybrid
      structures bind growth factors, promote the neurite outgrowth of hippocampal
      neurons in vitro, and have been implicated in the development of the brain. To
      investigate the expression of functional oversulfated DS structures in the brain,
      a novel monoclonal antibody (mAb), 2A12, was generated against DS (An-DS) from
      ascidian Ascidia nigra, which contains a unique iD disaccharide unit, iduronic
      acid (2-O-sulfate)alpha1-->3GalNAc(6-O-sulfate), as a predominant disaccharide.
      mAb 2A12 specifically reacted with the immunogen, and recognized iD-enriched
      decasaccharides as minimal structures. The 2A12 epitope was specifically observed
      in the hippocampus and cerebellum of the mouse brain on postnatal day 7, and the
      expression in the cerebellum disappeared in the adult brain, suggesting a
      spatiotemporally regulated expression of this epitope. Embryonic hippocampal
      neurons were immunopositive for 2A12, and the addition of the antibody to the
      culture medium significantly reduced the neurite growth of hippocampal neurons.
      In addition, two minimum 2A12-reactive decasaccharide sequences with multiple
      consecutive iD units were isolated from the An-DS chains, which exhibited
      stronger inhibitory activity against the binding of various growth factors and
      neurotrophic factors to immobilized embryonic pig brain CS/DS chains (E-CS/DS)
      than the intact E-CS/DS, suggesting that the 2A12 epitope at the neuronal surface
      acts as a receptor or co-receptor for these molecules. Thus, we have selected a
      unique antibody that recognizes iD-enriched oversulfated DS structures, which are
      implicated in the development of the hippocampus and cerebellum in the central
      nervous system. The antibody will also be applicable for investigating structural
      alterations in CS/DS in aging and pathological conditions.

PMID- 15849185
TI  - ATP-dependent rotation of mutant ATP synthases defective in proton transport.
AB  - During ATP hydrolysis, the gammaepsilon c10 complex (gamma and epsilon subunits
      and a c subunit ring formed from 10 monomers) of F0F1 ATPase (ATP synthase)
      rotates relative to the alpha3beta3delta ab2 complex, leading to proton transport
      through the interface between the a subunit and the c subunit ring. In this
      study, we replaced the two pertinent residues for proton transport, cAsp-61 and
      aArg-210 of the c and a subunits, respectively. The mutant enzymes exhibited
      lower ATPase activities than that of the wild type but exhibited ATP-dependent
      rotation in planar membranes, in which their original assemblies are maintained.
      The mutant enzymes were defective in proton transport, as shown previously. These
      results suggest that proton transport can be separated from rotation in ATP
      hydrolysis, although rotation ensures continuous proton transport by bringing the
      cAsp-61 and aArg-210 residues into the correct interacting positions.

PMID- 15849186
TI  - IpgB1 is a novel Shigella effector protein involved in bacterial invasion of host
      cells. Its activity to promote membrane ruffling via Rac1 and Cdc42 activation.
AB  - Shigella, the causative agent of bacillary dysentery, is capable of inducing the
      large scale membrane ruffling required for the bacterial invasion of host cells.
      Shigella secrete a subset of effectors via the type III secretion system (TTSS)
      into the host cells to induce membrane ruffling. Here, we show that IpgB1 is
      secreted via the TTSS into epithelial cells and plays a major role in producing
      membrane ruffles via stimulation of Rac1 and Cdc42 activities, thus promoting
      bacterial invasion of epithelial cells. The invasiveness of the ipgB1 mutant was
      decreased to less than 50% of the wild-type level (100%) in a gentamicin
      protection or plaque forming assay. HeLa cells infected with the wild-type or a
      IpgB1-hyperproducing strain developed membrane ruffles, with the invasiveness and
      the scale of membrane ruffles being comparable with the level of IpgB1 production
      in bacteria. Upon expression of EGFP-IpgB1 in HeLa cells, large membrane ruffles
      are extended, where the EGFP-IpgB1 was predominantly associated with the
      cytoplasmic membrane. The IpgB1-mediated formation of ruffles was significantly
      diminished by expressing Rac1 small interfering RNA and Cdc42 small interfering
      RNA or by treatment with GGTI-298, an inhibitor of the geranylgeranylation of Rho
      GTPases. When IpgB1 was expressed in host cells or wild-type Shigella-infected
      host cells, Rac1 and Cdc42 were activated. The results thus indicate that IpgB1
      is a novel Shigella effector involved in bacterial invasion of epithelial cells
      via the activation of Rho GTPases.

PMID- 15849187
TI  - Requirements for catalysis in mammalian glycogenin.
AB  - Glycogenin is a glycosyltransferase that functions as the autocatalytic initiator
      for the synthesis of glycogen in eukaryotic organisms. Prior structural work
      identified the determinants responsible for the recognition and binding of UDP
      glucose and the catalytic manganese ion and implicated two aspartic acid residues
      in the reaction mechanism for self-glucosylation. We examined the effects of
      substituting asparagine and serine for the aspartic acid residues at positions
      159 and 162. We also examined whether the truncation of the protein at residue
      270 (delta270) was compatible with its structural integrity and its functional
      role as the initiator for glycogen synthesis. The truncated form of the enzyme
      was indistinguishable from the wild-type enzyme by all measures of activity and
      could support glycogen accumulation in a glycogenin-deficient yeast strain.
      Substitution of aspartate 159 by either serine or asparagine eliminated self
      glucosylation and reduced trans-glucosylation activity by at least 260-fold but
      only reduced UDP-glucose hydrolytic activity by 4-14-fold. Substitution of
      aspartate 162 by either serine or asparagine eliminated self-glucosylation
      activity and reduced UDP-glucose hydrolytic activity by at least 190-fold. The
      trans-glucosylation of maltose was reduced to undetectable levels in the
      asparagine 162 mutant, whereas the serine 162 enzyme showed only an 18-30-fold
      reduction in its ability to trans-glucosylate maltose. These data support a role
      for aspartate 162 in the chemical step for the glucosyltransferase reaction and a
      role for aspartate 159 in binding and activating the acceptor molecule.

PMID- 15849189
TI  - Phosphatidylinositol phosphate kinase type Igamma directly associates with and
      regulates Shp-1 tyrosine phosphatase.
AB  - Tyrosine phosphorylation plays a critical role in many regulatory aspects of
      cellular signaling, and dephosphorylation of phosphotyrosine residues is crucial
      for termination of signals initiated by tyrosine kinases. Previous work has shown
      that the tyrosine kinase Src phosphorylates Tyr644 on phosphatidylinositol
      phosphate kinase type I (PIPKI) gamma661 in a focal adhesion kinase-dependent
      manner. Phosphorylation of this residue is essential for high affinity binding of
      PIPKI gamma661 to the focal adhesion protein talin and for targeting of PIPKI
      gamma661 to focal adhesions. A yeast two-hybrid screen performed with the C
      terminal 178-amino acid tail of PIPKI gamma661 identified an interaction with the
      phosphatase domain of the tyrosine phosphatase Shp-1. The interaction between
      PIPKI gamma661 and Shp-1 was confirmed via co-immunoprecipitation from HEK293
      cell lysates. In addition, Src-phosphorylated PIPKI gamma661 is a substrate for
      Shp-1, and Shp-1 modulates both the association between PIPKI gamma661 and talin
      and the targeting of PIPKI gamma661 to focal adhesions in mammalian cells.
      Finally, we showed that Shp-1 phosphatase activity is inhibited by the product of
      PIPKI gamma661, phosphatidylinositol 4,5-bisphosphate, in vitro. These combined
      results suggest a model in which the reciprocal actions of Src tyrosine kinase
      and Shp-1 tyrosine phosphatase dynamically regulate the association between PIPKI
      gamma661 and talin.

PMID- 15849190
TI  - Targeting the NAD7 subunit to mitochondria restores a functional complex I and a
      wild type phenotype in the Nicotiana sylvestris CMS II mutant lacking nad7.
AB  - The mitochondrial DNA of the Nicotiana sylvestris CMSII mutant carries a 72-kb
      deletion comprising the single copy nad7 gene that encodes the NAD7 subunit of
      the respiratory complex I (NADH-ubiquinone oxidoreductase). CMSII plants lack
      rotenone-sensitive complex I activity and are impaired in physiological and
      phenotypical traits. To check whether these changes directly result from the
      deletion of nad7, we constructed CMS transgenic plants (termed as CMSnad7)
      carrying an edited nad7 cDNA fused to the CAMV 35S promoter and to a
      mitochondrial targeting sequence. The nad7 sequence was transcribed and
      translated and the NAD7 protein directed to mitochondria in CMSnad7 transgenic
      plants, which recovered both wild type morphology and growth features. Blue
      native/SDS gel electrophoresis and enzymatic assays showed that, whereas fully
      assembled complex I was absent from CMSII mitochondria, a functional complex was
      present in CMSnad7 mitochondria. Furthermore, a supercomplex involving complex I
      and complex III was present in CMSnad7 as in the wild type. Taken together, these
      data demonstrate that lack of complex I in CMSII was indeed the direct
      consequence of the absence of nad7. Hence, NAD7 is a key element for complex
      assembly in plants. These results also show that allotopic expression from the
      nucleus can fully complement the lack of a mitochondrial-encoded complex I gene.

PMID- 15849192
TI  - Human telomerase reverse transcriptase immortalizes bovine lens epithelial cells
      and suppresses differentiation through regulation of the ERK signaling pathway.
AB  - Telomerase is a specialized reverse transcriptase that extends telomeres of
      eukaryotic chromosomes. The functional telomerase complex contains a telomerase
      reverse transcriptase catalytic subunit and a telomerase template RNA. We have
      previously demonstrated that human telomerase reverse transcriptase (hTERT)
      catalytic subunit is functionally compatible with a telomerase template RNA from
      rabbit. In this study, we show that hTERT is also functionally compatible with a
      telomerase template RNA from bovine. Introduction of hTERT into bovine lens
      epithelial cells (BLECs) provides the transfected cells telomerase activity. The
      expressed hTERT in BLECs supports normal growth of the transfected cells for 108
      population doublings so far, and these cells are still extremely healthy in both
      morphology and growth. In contrast, the vector-transfected cells display growth
      crisis after 20 population doublings. These cells run into cellular senescence
      due to shortening of the telomeres and also commit differentiation as indicated
      by the accumulation of the differentiation markers, beta-crystallin and filensin.
      hTERT prevents the occurrence of both events. By synthesizing new telomere, hTERT
      prevents replicative senescence, and through regulation of MEK/ERK, protein
      kinase C, and protein kinase A and eventual suppression of the MEK/ERK signaling
      pathway, hTERT inhibits differentiation of BLECs. Our finding that hTERT can
      suppress RAS/RAF/MEK/ERK signaling pathway to prevent differentiation provides a
      novel mechanism to explain how hTERT regulates cell differentiation.

PMID- 15849191
TI  - Keratocan, a cornea-specific keratan sulfate proteoglycan, is regulated by
      lumican.
AB  - Lumican is an extracellular matrix glycoprotein widely distributed in mammalian
      connective tissues. Corneal lumican modified with keratan sulfate constitutes one
      of the major proteoglycans of the stroma. Lumican-null mice exhibit altered
      collagen fibril organization and loss of corneal transparency. A closely related
      protein, keratocan, carries the remaining keratan sulfate of the cornea, but
      keratocan-null mice exhibit a less severe corneal phenotype. In the current
      study, we examined the effect of lumican overexpression in corneas of wild type
      mice. These mice showed no alteration in collagen organization or transparency
      but had increased keratocan expression at both protein and mRNA levels. Corneas
      of lumican-null mice showed decreased keratocan. This coupling of keratocan
      expression with lumican also was observed after intrastromal injection of a
      lumican expression minigene into the corneal stroma of Lum-/- mice. Small
      interfering RNA knockdown of lumican in vitro reduced keratocan expression,
      whereas co-injection of a lumican-expressing minigene with a beta-galactosidase
      reporter driven by the keratocan promoter demonstrated an increase of keratocan
      transcriptional activity in response to lumican expression in Lum-/- corneas in
      vivo. These observations demonstrate that lumican has a novel regulatory role in
      keratocan expression at the transcriptional level. Such results help provide an
      explanation for the differences in severity of corneal manifestation found in Lum
      /- and Kera-/- mice. The results also suggest a critical level of small
      proteoglycans to be essential for collagen organization but that overabundance is
      not detrimental to extracellular matrix morphogenesis.

PMID- 15849194
TI  - p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its
      mitochondrial localization, phosphorylation of BAD, and Bcl-2 association.
AB  - Raf-1 protects cells from apoptosis, independently of its signals to MEK and ERK,
      by translocating to the mitochondria where it binds Bcl-2 and displaces BAD.
      However, the answer to the question of how Raf-1 is normally lured to the
      mitochondria and becomes activated remains elusive. p21-activated protein kinases
      (Paks) are serine/threonine protein kinases that phosphorylate Raf-1 at Ser-338
      and Ser-339. Here we elucidate the molecular mechanism through which Pak1 signals
      to BAD through a Raf-1-activated pathway. Upon phosphorylation by Pak1, Raf-1
      translocates to mitochondria and phosphorylates BAD at Ser-112. Moreover, the
      mitochondrial translocation of Raf-1 and the interaction between Raf-1 and Bcl-2
      are regulated by Raf-1 phosphorylation at Ser-338/Ser-339. Notably, we show that
      formation of a Raf-1-Bcl-2 complex coincides with loss of an interaction between
      Bcl-2 and BAD. These signals are specific for Pak1, because Src-activated Raf-1
      only stimulates the MAP kinase cascade. Thus, our data identify the molecular
      connections of a Pak1-Raf-1-BAD pathway that is involved in cell survival
      signaling.

PMID- 15849195
TI  - Deficiency of ADAP/Fyb/SLAP-130 destabilizes SKAP55 in Jurkat T cells.
AB  - ADAP (adhesion and degranulation-promoting adaptor protein) and SKAP55 (Src
      kinase-associated phosphoprotein of 55 kDa) are T cell adaptors that mediate
      inside-out signaling from the T cell antigen receptor to integrins, giving rise
      to increased integrin affinity/avidity and formation of the immunological synapse
      between the T cell and the antigen-presenting cell. These two proteins are
      tightly and constitutively associated with one another, and their ability to
      interact is required for inside-out signaling. Here we show in an ADAP-deficient
      Jurkat T cell line that the co-dependence of ADAP and SKAP55 extends beyond their
      functional and physical interactions and show that SKAP55 protein is unstable in
      the absence of ADAP. Restoration of ADAP to the ADAP-deficient Jurkat T cell line
      restores SKAP55 expression by causing a 5-fold decrease in the rate of SKAP55
      proteolysis. Inactivation of the Src homology 3 domain of SKAP55, which mediates
      the association between SKAP55 with ADAP, blocks the protective effect of ADAP.
      The half-life of SKAP55, in the absence of ADAP, is approximately 15-20 min,
      increasing to 90 min in the presence of ADAP. This is a remarkably rapid rate of
      turnover for a signaling protein and suggests the possibility that stimuli that
      signal for the stabilization of SKAP55 may play an important role in T cell
      adhesion and conjugate formation.

PMID- 15849193
TI  - Repression of bone morphogenetic protein and activin-inducible transcription by
      Evi-1.
AB  - Smads, key effectors of transforming growth factor (TGF)-beta, activin, and bone
      morphogenetic protein (BMP) signaling, regulate gene expression and interact with
      coactivators and corepressors that modulate Smad activity. The corepressor Evi-1
      exerts its oncogenic effects by repressing TGF-beta/Smad3-mediated transcription,
      thereby blocking TGF-beta-induced growth arrest. Because Evi-1 interacts with the
      highly conserved MH2 domain of Smad3, we investigated the physical and functional
      interaction of Evi-1 with Smad1 and Smad2, downstream targets of BMP and activin
      signaling, respectively. Evi-1 interacted with and repressed the receptor
      activated transcription through Smad1 and Smad2, similarly to Smad3. In addition,
      Evi-1 repressed BMP/Smad1- and activin/Smad2-mediated induction of endogenous
      Xenopus gene expression, suggesting a role of repression of BMP and activin
      signals by Evi-1 in vertebrate embryogenesis. Evi-1 also repressed the induction
      of endogenous Smad7 expression by TGF-beta family ligands. In the course of these
      studies, we observed Evi-1 repression of Smad transactivation even when Smad
      binding to DNA was kept constant. We therefore explored the mechanism of Evi-1
      repression of TGF-beta family-inducible transcription. Evi-1 repression did not
      result from displacement of Smad binding to DNA or to CREB-binding protein but
      from the recruitment of Evi-1 by Smad3 and CREB-binding protein to DNA. Following
      TGF-beta stimulation, Evi-1 and the associated corepressor CtBP were recruited to
      the endogenous Smad7 promoter. Evi-1 recruitment to the promoter decreased TGF
      beta-induced histone acetylation, coincident with its repression of Smad7 gene
      expression. In this way, Evi-1 acts as a general Smad corepressor to inhibit TGF
      beta-, activin-, and BMP-inducible transcription.

PMID- 15849188
TI  - Transcriptional profiles of the human pathogenic fungus Paracoccidioides
      brasiliensis in mycelium and yeast cells.
AB  - Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis, a
      disease that affects 10 million individuals in Latin America. This report depicts
      the results of the analysis of 6,022 assembled groups from mycelium and yeast
      phase expressed sequence tags, covering about 80% of the estimated genome of this
      dimorphic, thermo-regulated fungus. The data provide a comprehensive view of the
      fungal metabolism, including overexpressed transcripts, stage-specific genes, and
      also those that are up- or down-regulated as assessed by in silico electronic
      subtraction and cDNA microarrays. Also, a significant differential expression
      pattern in mycelium and yeast cells was detected, which was confirmed by Northern
      blot analysis, providing insights into differential metabolic adaptations. The
      overall transcriptome analysis provided information about sequences related to
      the cell cycle, stress response, drug resistance, and signal transduction
      pathways of the pathogen. Novel P. brasiliensis genes have been identified,
      probably corresponding to proteins that should be addressed as virulence factor
      candidates and potential new drug targets.

PMID- 15849196
TI  - SP3/SP1 transcription activity regulates specific expression of collagen type X
      in hypertrophic chondrocytes.
AB  - Previously, we have shown that two non-canonical specificity protein (SP)-binding
      sites within the proximal promoter (nucleotide (nt) -139 to +5) of the chicken
      Col10a1 gene are involved in conferring tissue-specific expression of type X
      collagen to hypertrophic chondrocytes. In the present study, we examined the role
      of SP3/SP1 transcription factors in the regulation of the Col10a1 promoter. The
      SP3/SP1 ratio is higher in hypertrophic versus non-hypertrophic chondrocytes, due
      to the significant decrease in SP1 in hypertrophic cells detected by real-time
      PCR and Western blot analyses. Functional analyses by transfection-mediated
      overexpression of SP1 and SP3 suggest that SP1 inhibits the Col10a1 promoter.
      This effect is negated by an interaction with SP3 in hypertrophic chondrocytes.
      Additionally, mutation analysis showed that the 40-bp intervening sequence (nt 
      115 to -75) is required for expression of the Col10a1 gene. In this sequence, a
      binding site for Dlx5/6 transcription factors (nt -99 to -87) retards a protein
      specific for hypertrophic chondrocytes in electrophoretic mobility shift assay.
      Endogenous levels of Dlx5 are 3-fold higher in hypertrophic versus non
      hypertrophic cells by real-time PCR analysis, and overexpression of Dlx5 in non
      hypertrophic chondrocytes activates the proximal Col10a1 promoter 3-fold. These
      results indicate that the SP3/SP1 ratio and Dlx5 are important regulators of the
      proximal Col10a1 promoter in hypertrophic cartilage and suggest that interactions
      between SP3 and SP1 regulate expression of different types of collagen during
      chondrocyte differentiation.

PMID- 15849197
TI  - N-linked keratan sulfate in the aggrecan interglobular domain potentiates
      aggrecanase activity.
AB  - Keratan sulfate is thought to influence the cleavage of aggrecan by
      metalloenzymes. We have therefore produced a recombinant substrate, substituted
      with keratan sulfate, suitable for the study of aggrecanolysis in vitro.
      Recombinant human G1-G2 was produced in primary bovine keratocytes using a
      vaccinia virus expression system. Following purification and digestion with
      specific hydrolases, fluorophore-assisted carbohydrate electrophoresis was used
      to confirm the presence of the monosulfated Gal-GlcNAc6S and GlcNAc6s-Gal
      disaccharides and the disulfated Gal6S-GlcNAc6S disaccharides of keratan sulfate.
      Negligible amounts of fucose or sialic acid were detected, and the level of
      unsulfated disaccharides was minimal. Treatment with keratanases reduced the size
      of the recombinant G1-G2 by approximately 5 kDa on SDS-PAGE. Treatment with N
      glycosidase F also reduced the size of G1-G2 by approximately 5 kDa and
      substantially reduced G1-G2 immunoreactivity with monoclonal antibody 5-D-4,
      indicating that keratan sulfate on the recombinant protein is N-linked. Cleavage
      of G1-G2 by aggrecanase was markedly reduced when keratan sulfate chains were
      removed by treatment with keratanase, keratanase II, endo-beta-galactosidase, or
      N-glycosidase F. These results indicate that modification of oligosaccharides in
      the aggrecan interglobular domain with keratan sulfate, most likely at asparagine
      residue 368, potentiates aggrecanase activity in this part of the core protein.

PMID- 15849198
TI  - Bruton's tyrosine kinase is involved in p65-mediated transactivation and
      phosphorylation of p65 on serine 536 during NFkappaB activation by
      lipopolysaccharide.
AB  - Bruton's tyrosine kinase (Btk) has recently been shown to participate in the
      induction of nuclear factor kappaB (NFkappaB)-dependent gene expression by the
      lipopolysaccharide (LPS) receptor Toll-like receptor-4 (TLR4). In this study we
      have examined the mechanism whereby Btk participates in this response. Treatment
      of the murine monocytic cell line Raw264.7 with LFM-A13, a specific Btk
      inhibitor, blocked LPS-induced NFkappaB-dependent reporter gene expression but
      not IkappaB alpha degradation. Transient transfection of HEK293 cells with Btk
      had no effect on NFkappaB-dependent reporter gene expression but strongly
      promoted transactivation of a reporter gene by a p65-Gal4 fusion protein. IkappaB
      alpha degradation activated by LPS was intact in macrophages from X-linked
      immunodeficiency (Xid) mice, which contain inactive Btk. Transfection of cells
      with a dominant negative form of Btk (BtkK430R) inhibited LPS-driven p65 mediated
      transactivation. Additionally LFM-A13 impaired phosphorylation of serine 536 on
      p65 induced by LPS in HEK293-TLR4 cells, and in Xid macrophages this response was
      impaired. This study therefore reveals a novel function for Btk. It is required
      for the signaling pathway activated by TLR4, which culminates in phosphorylation
      of p65 on serine 536 promoting transactivation by NFkappaB.

PMID- 15849199
TI  - Calibration of the channel that determines the omega-hydroxylation
      regiospecificity of cytochrome P4504A1: catalytic oxidation of 12-HALODOdecanoic
      acids.
AB  - The fatty acid omega-hydroxylation regiospecificity of CYP4 enzymes may result
      from presentation of the terminal carbon to the oxidizing species via a narrow
      channel that restricts access to the other carbon atoms. To test this hypothesis,
      the oxidation of 12-iodo-, 12-bromo-, and 12-chlorododecanoic acids by
      recombinant CYP4A1 has been examined. Although all three 12-halododecanoic acids
      bind to CYP4A1 with similar dissociation constants, the 12-chloro and 12-bromo
      fatty acids are oxidized to 12-hydroxydodecanoic acid and 12-oxododecanoic acid,
      whereas the 12-iodo analogue is very poorly oxidized. Incubations in H(2)(18)(2)O
      show that the 12-hydroxydodecanoic acid oxygen derives from water, whereas that
      in the aldehyde derives from O(2). The alcohol thus arises from oxidation of the
      halide to an oxohalonium species that is hydrolyzed by water, whereas the
      aldehyde arises by a conventional carbon hydroxylation-elimination mechanism. No
      irreversible inactivation of CYP4A1 is observed during 12-halododecanoic acid
      oxidation. Control experiments show that CYP2E1, which has an omega-1
      regiospecificity, primarily oxidizes 12-halododecanoic acids to the omega
      aldehyde rather than alcohol product. Incubation of CYP4A1 with 12,12-[(2)H](2)
      12-chlorododecanoic acid causes a 2-3-fold increase in halogen versus carbon
      oxidation. The fact that the order of substrate oxidation (Br > Cl >> I)
      approximates the inverse of the intrinsic oxidizability of the halogen atoms is
      consistent with presentation of the halide terminus via a channel that
      accommodates the chloride and bromide but not iodide atoms, which implies an
      effective channel diameter greater than 3.90 Angstroms but smaller than 4.30
      Angstroms.

PMID- 15849200
TI  - Role of the GYVG pore motif of HslU ATPase in protein unfolding and translocation
      for degradation by HslV peptidase.
AB  - HslVU is an ATP-dependent protease consisting of HslU ATPase and HslV peptidase.
      In an HslVU complex, the central pores of HslU hexamer and HslV dodecamer are
      aligned and the proteolytic active sites are sequestered in the inner chamber of
      HslV. Thus, the degradation of natively folded proteins requires unfolding and
      translocation processes for their access into the proteolytic chamber of HslV. A
      highly conserved GYVG(93) sequence constitutes the central pore of HslU ATPase.
      To determine the role of the pore motif on protein unfolding and translocation,
      we generated various mutations in the motif and examined their effects on the
      ability of HslU in supporting the proteolytic activity of HslV against three
      different substrates: SulA as a natively folded protein, casein as an unfolded
      polypeptide, and a small peptide. Flexibility provided by Gly residues and
      aromatic ring structures of the 91st amino acid were essential for degradation of
      SulA. The same structural features of the GYVG motif were highly preferred,
      although not essential, for degradation of casein. In contrast, none of the
      features were required for peptide hydrolysis. Mutations in the GYVG motif of
      HslU also showed marked influence on its ATPase activity, affinity to ADP, and
      interaction with HslV. These results suggest that the GYVG motif of HslU plays
      important roles in unfolding of natively folded proteins as well as in
      translocation of unfolded proteins for degradation by HslV. These results also
      implicate a role of the pore motif in ATP cleavage and in the assembly of HslVU
      complex.

PMID- 15849201
TI  - Caspase-dependent and -independent activation of acid sphingomyelinase signaling.
AB  - Recent evidence suggests clustering of plasma membrane rafts into ceramide
      enriched platforms serves as a transmembrane signaling mechanism for a subset of
      cell surface receptors and environmental stresses (Grassme, H., Jekle, A.,
      Riehle, A., Schwarz, H., Berger, J., Sandhoff, K., Kolesnick, R., and Gulbins, E.
      (2001) J. Biol. Chem. 276, 20589-20596; Cremesti, A., Paris, F., Grassme, H.,
      Holler, N., Tschopp, J., Fuks, Z., Gulbins, E., and Kolesnick, R. (2001) J. Biol.
      Chem. 276, 23954-23961). Translocation of the secretory form of acid
      sphingomyelinase (ASMase) into microscopic rafts generates therein the ceramide
      that drives raft coalescence. This process serves to feed forward Fas activation,
      with approximately 2% of full caspase 8 activation sufficient for maximal ASMase
      translocation, leading to death-inducing signaling complex formation within
      ceramide-rich platforms, and apoptosis. Here we report that treatment of Jurkat T
      cells with UV-C also induces ASMase translocation into rafts within 1 min,
      catalyzing sphingomyelin hydrolysis to ceramide and raft clustering. In contrast
      to Fas, UV-induced ASMase translocation and activation were caspase-independent.
      Nonetheless, ceramide-rich platforms promoted UV-C-induced death signaling,
      because ASMase inhibition or raft disruption inhibited apoptosis, improving
      clonogenic cell survival. These studies thus define two distinct mechanisms for
      biologically relevant ASMase activation within rafts; a Fas-mediated mechanism
      dependent upon caspase 8 and FADD, and a UV-induced mechanism independent of
      caspase activation. Consistent with this notion, genetic depletion or
      pharmacologic inhibition of caspase 8 or FADD, which render Jurkat cells
      incapable of sphingolipid signaling and apoptosis upon Fas ligation, did not
      impair these events upon UV-C stimulation.

PMID- 15849202
TI  - Nuclear phospholipase C beta1 (PLCbeta1) affects CD24 expression in murine
      erythroleukemia cells.
AB  - Inositide-specific phospholipase C (PLC) beta1 is a key enzyme in nuclear lipid
      signal transduction affecting cell cycle progression and may be directly involved
      in regulation of gene expression and hematopoiesis. By microarrays, we compared
      the effect of nuclear PLCbeta1 overexpression with that of PLC M2b cytoplasmatic
      mutant, which is exclusively located in the cytoplasm, in murine erythroleukemia
      cells. Out of 9000 genes analyzed, the CD24 gene, coding for an antigen involved
      in differentiation and hematopoiesis as well, was up-regulated in cells
      overexpressing nuclear PLCbeta1 as compared with both cells overexpressing the
      M2b cytoplasmatic mutant and the wild type cells. Here we show that nuclear
      PLCbeta1 up-regulated the expression of CD24. The correlation was strengthened by
      the observation that when PLCbeta1 expression was silenced by means of small
      interfering RNA, CD24 expression was down-regulated. We also demonstrated that
      PLCbeta1-dependent up-modulation of CD24 was mediated, at least in part, at the
      transcriptional level, in that PLCbeta1 affected the CD24 promoter activity.
      Moreover, the up-regulation of CD24 was higher during erythroid differentiation
      of murine erythroleukemia cells. Altogether our findings, obtained by combining
      microarrays, phenotypic analysis, and small interfering RNA technology, identify
      CD24 as an molecular effector of nuclear PLCbeta1 signaling pathway in murine
      erythroleukemia cells and strengthen the contention that nuclear PLCbeta1
      constitutes a key step in erythroid differentiation in vitro.

PMID- 15849204
TI  - Trends in prevalence of asthma and allergy in Finnish young men: nationwide
      study, 1966-2003.

PMID- 15849205
TI  - Day care in infancy and risk of childhood acute lymphoblastic leukaemia: findings
      from UK case-control study.
AB  - OBJECTIVE: To test the hypothesis that reduced exposure to common infections in
      the first year of life increases the risk of developing acute lymphoblastic
      leukaemia. Design and setting The United Kingdom childhood cancer study (UKCCS)
      is a large population based case-control study of childhood cancer across 10
      regions of the UK. PARTICIPANTS: 6305 children (aged 2-14 years) without cancer;
      3140 children with cancer (diagnosed 1991-6), of whom 1286 had acute
      lymphoblastic leukaemia (ALL). MAIN OUTCOME MEASURE: Day care and social activity
      during the first year of life were used as proxies for potential exposure to
      infection in infancy. RESULTS: Increasing levels of social activity were
      associated with consistent reductions in risk of ALL; a dose-response trend was
      seen. When children whose mothers reported no regular activity outside the family
      were used as the reference group, odds ratios for increasing levels of activity
      were 0.73 (95% confidence interval 0.62 to 0.87) for any social activity, 0.62
      (0.51 to 0.75) for regular day care outside the home, and 0.48 (0.37 to 0.62) for
      formal day care (attendance at facility with at least four children at least
      twice a week) (P value for trend < 0.001). Although not as striking, results for
      non-ALL malignancies showed a similar pattern (P value for trend < 0.001). When
      children with non-ALL malignancies were taken as the reference group, a
      significant protective effect for ALL was seen only for formal day care (odds
      ratio = 0.69, 0.51 to 0.93; P = 0.02). Similar results were obtained for B cell
      precursor common ALL and other subgroups, as well as for cases diagnosed above
      and below age 5 years. CONCLUSION: These results support the hypothesis that
      reduced exposure to infection in the first few months of life increases the risk
      of developing acute lymphoblastic leukaemia.

PMID- 15849206
TI  - Metformin and reduced risk of cancer in diabetic patients.

PMID- 15849207
TI  - Efficacy of prophylactic ketamine in preventing postoperative shivering.
AB  - BACKGROUND: Treatment with ketamine and pethidine is effective in postoperative
      shivering. The aim of this study was to compare the efficacy of low-dose
      prophylactic ketamine with that of pethidine or placebo in preventing
      postoperative shivering. METHODS: A prospective randomized double-blind study
      involved 90 ASA I and II patients undergoing general anaesthesia. Patients were
      randomly allocated to receive normal saline (Group S, n=30), pethidine 20 mg
      (Group P, n=30) or ketamine 0.5 mg kg(-1) (Group K, n=30) intravenously 20 min
      before completion of surgery. The anaesthesia was induced with propofol 2 mg kg(
      1), fentanyl 1 microg kg(-1) and vecuronium 0.1 mg kg(-1). It was maintained with
      sevoflurane 2-4% and nitrous oxide 60% in oxygen. Tympanic temperature was
      measured immediately after induction of anaesthesia, 30 min after induction and
      before administration of the study drug. An investigator, blinded to the
      treatment group, graded postoperative shivering using a four-point scale and
      postoperative pain using a visual analogue scale (VAS) ranging between 0 and 10.
      RESULTS: The three groups did not differ significantly regarding patient
      characteristics. The number of patients shivering on arrival in the recovery
      room, and at 10 and 20 min after operation were significantly less in Groups P
      and K than in Group S. The time to first analgesic requirement in Group S was
      shorter than in either Group K or Group P (P<0.005). There was no difference
      between the three groups regarding VAS pain scores. CONCLUSION: Prophylactic low
      dose ketamine was found to be effective in preventing postoperative shivering.

PMID- 15849208
TI  - Procalcitonin, interleukin 6 and systemic inflammatory response syndrome (SIRS):
      early markers of postoperative sepsis after major surgery.
AB  - BACKGROUND: Patients who undergo major surgery for cancer are at high risk of
      postoperative sepsis. Early markers of septic complications would be useful for
      diagnosis and therapeutic management in patients with postoperative sepsis. The
      aim of this study was to investigate the association between early (first
      postoperative day) changes in interleukin 6 (IL-6), procalcitonin (PCT) and C
      reactive protein (CRP) serum concentrations and the occurrence of subsequent
      septic complications after major surgery. METHODS: Serial blood samples were
      collected from 50 consecutive patients for determination of IL-6, PCT and CRP
      serum levels. Blood samples were obtained on the morning of surgery and on the
      morning of the first postoperative day. RESULTS: Sixteen patients developed
      septic complications during the first five postoperative days (group 1), and 34
      patients developed no septic complications (group 2). On day 1, PCT and IL-6
      levels were significantly higher in group 1 (P-values of 0.003 and 0.006,
      respectively) but CRP levels were similar. An IL-6 cut-off point set at 310 pg
      ml(-1) yielded a sensitivity of 90% and a specificity of 58% to differentiate
      group 1 patients from group 2 patients. When associated with the occurrence of
      SIRS on day 1 these values reached 100% and 79%, respectively. A PCT cut-off
      point set at 1.1 ng ml(-1) yielded a sensitivity of 81% and a specificity of 72%.
      When associated with the occurrence of SIRS on day 1, these values reached 100%
      and 86%, respectively. CONCLUSIONS: PCT and IL-6 appear to be early markers of
      subsequent postoperative sepsis in patients undergoing major surgery for cancer.
      These findings could allow identification of postoperative septic complications.

PMID- 15849209
TI  - Effect of intrathecal diamorphine on block height during spinal anaesthesia for
      Caesarean section with bupivacaine.
AB  - BACKGROUND: Opioid analgesics are commonly added to intrathecal bupivacaine to
      improve patient comfort during Caesarean section under spinal anaesthesia, and
      provide post-operative pain relief. We sought to discover if the addition of
      diamorphine influenced block height when given with 0.5% w/v hyperbaric
      bupivacaine. METHOD: Eighty ASA I and II women of at least 37 weeks gestation and
      planned for elective Caesarean section under combined spinal-epidural anaesthesia
      were recruited. They were randomized into two groups to receive intrathecal
      hyperbaric bupivacaine 0.5% at an initial dose of 13 mg, with the next dose
      determined by the response of the previous patient (dose interval 1 mg). One
      group also received diamorphine 400 microg intrathecally. If a block height of T5
      to blunt light touch had been achieved after 20 min, the block was deemed
      effective. A difference in the ED50 for hyperbaric bupivacaine between the groups
      would indicate that diamorphine influenced block height. Intraoperative patient
      discomfort and need for analgesic supplementation was noted. RESULTS: The median
      effective dose (ED50) to achieve a T5 block to light touch for Caesarean section
      using hyperbaric bupivacaine 0.5% was 9.95 mg [95% confidence interval (CI) 9.0
      10.90] and with the addition of diamorphine it was 9.3 mg (95% CI 8.15-10.40),
      while the ED95 was 13.55 mg (95% CI 10.10-17.0) and 13.6 mg (95% CI 9.15-18.05),
      respectively. Five women who had received intrathecal diamorphine and 13 who had
      not received diamorphine needed intraoperative supplementation (not significant).
      CONCLUSION: The addition of intrathecal diamorphine does not appear to influence
      block height.

PMID- 15849210
TI  - Severe hypertension after stellate ganglion block.
AB  - Haemodynamic effects may occur after stellate ganglion block (SGB) arising from
      autonomic imbalance and local anaesthetic infiltration to barosensitive areas. We
      report seven patients who developed severe hypertension (systolic arterial
      pressure >200 mm Hg) after SGB in our pain clinic service. We postulate that
      diffusion of the local anaesthetic along the carotid sheath may produce vagal
      blockade causing unopposed sympathetic activity as a result of attenuation of the
      baroreceptor reflex. We recommend close monitoring of arterial pressure
      measurement in patients who received SGB.

PMID- 15849211
TI  - Coexpression of RTI40 with alveolar epithelial type II cell proteins in lungs
      following injury: identification of alveolar intermediate cell types.
AB  - Injured alveolar epithelial type (AT) I cells are replaced following the
      proliferation and transformation of ATII cells to new ATI cells. RTI(40) is an
      ATI cell-specific protein required for normal lung development. We hypothesized
      that intermediate cell types in the ATII-to-ATI cell transformation would
      coexpress RTI(40) and ATII cell-selective proteins. To test this hypothesis, we
      used a rat model of Staphylococcus aureus-induced acute lung injury and a panel
      of ATI and ATII cell-specific and -selective antibodies. S. aureus induced an
      acute inflammatory reaction that was resolving by day 3 postinoculation. At day 3
      postinoculation, the alveolar wall was thickened secondary to ATII cell
      hyperplasia. With the use of confocal microscopy, there was a fivefold increase
      in the fractional surface area of alveolar walls stained with ATII cell membrane
      proteins (RTII(70) and MMC4) and a decrease in the fractional surface area
      associated with RTI(40)-expressing cells. S. aureus-treated lungs also contained
      unique cell types that coexpressed the RTI(40) and ATII markers
      RTI(40)/MMC4/RTII(70)- and RTI(40)/MMC4-positive cells. These cells were not
      observed in control lungs. RTI(40)/MMC4-positive cells were also found in
      cultured ATII cells before they transformed to an ATI-like phenotype. Our data
      suggest that RTI(40)/MMC4/RTII(70)- and RTI(40)/MMC4-positive cells are
      intermediates in the ATII-to-ATI cell transformation. These data also suggest
      that the coexpression of RTI(40) with ATII cell proteins may be used to identify
      and investigate ATII cell transdifferentiation to ATI cells following injury.

PMID- 15849212
TI  - Scavenger receptor class A type I/II (CD204) null mice fail to develop fibrosis
      following silica exposure.
AB  - Alveolar macrophages express the class A scavenger receptor (CD204) (Babaev VR,
      Gleaves LA, Carter KJ, Suzuki H, Kodama T, Fazio S, and Linton MF. Arterioscler
      Thromb Vasc Biol 20: 2593-2599, 2000); yet its role in vivo in lung defense
      against environmental particles has not been clearly defined. In the current
      study, CD204 null mice (129Sv background) were used to investigate the link
      between CD204 and downstream events of inflammation and fibrosis following silica
      exposure in vivo. CD204-/- macrophages were shown to recognize and uptake silica
      in vitro, although this response was attenuated compared with 129Sv wild-type
      mice. The production of tumor necrosis factor-alpha in lavage fluid was
      significantly enhanced in CD204 null mice compared with wild-type mice following
      silica exposure. Moreover, after exposure to environmental particles, CD204-/-
      macrophages exhibited improved cell viability in a dose-dependent manner compared
      with wild-type macrophages. Finally, histopathology from a murine model of
      chronic silicosis in 129Sv wild-type mice displayed typical focal lesions,
      interstitial thickening with increased connective tissue matrix, and cellular
      infiltrate into air space. In contrast, CD204-/- mice exhibited little to no
      deposition of collagen, yet they demonstrated enhanced accumulation of
      inflammatory cells largely composed of neutrophils. Our findings point to an
      important role of CD204 in mounting an efficient and appropriately regulated
      immune response against inhaled particles. Furthermore, these results indicate
      that the functions of CD204 are critical to the development of fibrosis and the
      resolution of inflammation.

PMID- 15849213
TI  - PKA delivery to the distal lung air spaces increases alveolar liquid clearance
      after isoproterenol-induced alveolar epithelial PKA desensitization.
AB  - Isoproterenol (Iso) infusion for 48 h in rats decreases the ability of beta
      adrenoceptor (beta-AR) agonists to increase alveolar liquid clearance (ALC). An
      impairment in protein kinase A (PKA) function appears to be critical in producing
      the desensitized ALC response. To test this hypothesis, we used a novel protein
      delivery reagent (Chariot, Active Motif) to deliver either the PKA catalytic
      subunit or the PKA holoenzyme to the distal lung epithelium of Iso-infused rats
      (400 microg.kg(-1).h(-1), 48 h). After this infusion, ALC was measured by mass
      balance over 2 h. ALC in Iso-infused rats was 27.9% (SD 5.8) of instilled volume
      absorbed. Delivery of the catalytic PKA subunit to Iso-infused rats increased ALC
      to 47.7% (SD 8.9) (P < 0.05). ALC in Iso-infused rats delivered the inactive PKA
      holoenzyme [29.6% (SD 2.5)] was not increased above baseline values. Subsequent
      holoenzyme activation by intravenous infusion of the stable cAMP analog Sp-8
      Bromo-cAMPS increased ALC to 41.7% (SD 8.8) (P < 0.05). Immunohistochemical
      localization of Chariot-delivered PKA revealed staining in the alveolar and
      distal airway epithelium. These data indicate that protein delivery reagents can
      be used to rapidly deliver biologically active proteins to the distal lung
      epithelium and that PKA desensitization may be an important rate-limiting event
      in the development of Iso-induced desensitization of the alveolar epithelial beta
      AR signaling pathway.

PMID- 15849214
TI  - Neutrophil elastase stimulates MUC1 gene expression through increased Sp1 binding
      to the MUC1 promoter.
AB  - We previously reported MUC1 was a cell surface receptor for Pseudomonas
      aeruginosa, and binding of bacteria to cells was significantly reduced by
      pretreatment with neutrophil elastase (NE) (Lillehoj EP, Hyun SW, Kim BT, Zhang
      XG, Lee DI, Rowland S, and Kim KC. Am J Physiol Lung Cell Mol Physiol 280: L181
      L187, 2001). The current study was conducted to ascertain NE effects on MUC1 gene
      transcription, and MUC1 protein synthesis and degradation. A549 human lung
      carcinoma cells treated with NE exhibited significantly higher MUC1 protein
      levels in detergent lysates compared with cells treated with vehicle alone. Also,
      MUC1 protein shed into cell-conditioned medium was rapidly and completely
      degraded by NE. Actinomycin D blocked NE-stimulated increase in MUC1 protein
      expression, suggesting a mechanism of increased gene transcription that was
      confirmed by measurement of quantitatively greater MUC1 mRNA levels in NE-treated
      cells compared with controls. However, NE did not alter MUC1 mRNA stability,
      implying increased de novo transcription induced by the protease. NE increased
      promoter activity in A549 cells transfected with MUC1 gene promoter-luciferase
      reporter plasmid. This effect of NE was completely blocked by mithramycin A, an
      inhibitor of Sp1, as well as mutation of one of the putative Sp1 binding sites in
      MUC1 promoter located at -99/-90 relative to transcription initiation site. EMSA
      revealed NE enhanced binding of Sp1 to this 10-bp segment in a time-dependent
      manner. These results indicate the increase in MUC1 gene transcription by NE is
      mediated through increase in Sp1 binding to -99/-90 segment of MUC1 promoter.

PMID- 15849215
TI  - A theoretical model of restriction endonuclease NlaIV in complex with DNA,
      predicted by fold recognition and validated by site-directed mutagenesis and
      circular dichroism spectroscopy.
AB  - Restriction enzymes (REases) are commercial reagents commonly used in DNA
      manipulations and mapping. They are regarded as very attractive models for
      studying protein-DNA interactions and valuable targets for protein engineering.
      Their amino acid sequences usually show no similarities to other proteins, with
      rare exceptions of other REases that recognize identical or very similar
      sequences. Hence, they are extremely hard targets for structure prediction and
      modeling. NlaIV is a Type II REase, which recognizes the interrupted palindromic
      sequence GGNNCC (where N indicates any base) and cleaves it in the middle,
      leaving blunt ends. NlaIV shows no sequence similarity to other proteins and
      virtually nothing is known about its sequence-structure-function relationships.
      Using protein fold recognition, we identified a remote relationship between NlaIV
      and EcoRV, an extensively studied REase, which recognizes the GATATC sequence and
      whose crystal structure has been determined. Using the 'FRankenstein's monster'
      approach we constructed a comparative model of NlaIV based on the EcoRV template
      and used it to predict the catalytic and DNA-binding residues. The model was
      validated by site-directed mutagenesis and analysis of the activity of the
      mutants in vivo and in vitro as well as structural characterization of the wild
      type enzyme and two mutants by circular dichroism spectroscopy. The structural
      model of the NlaIV-DNA complex suggests regions of the protein sequence that may
      interact with the 'non-specific' bases of the target and thus it provides insight
      into the evolution of sequence specificity in restriction enzymes and may help
      engineer REases with novel specificities. Before this analysis was carried out,
      neither the three-dimensional fold of NlaIV, its evolutionary relationships or
      its catalytic or DNA-binding residues were known. Hence our analysis may be
      regarded as a paradigm for studies aiming at reducing 'white spaces' on the
      evolutionary landscape of sequence-function relationships by combining
      bioinformatics with simple experimental assays.

PMID- 15849216
TI  - Understanding the relationship between the primary structure of proteins and
      their amyloidogenic propensity: clues from inclusion body formation.
AB  - Amyloid formation is dependent to a considerable extent on the amino acid
      sequence of the protein. The present study delineates certain sequence-dependent
      features that are correlated with amyloidogenic propensity. The analyses indicate
      that amyloid formation is favored by lower thermostability and increased half
      life of the protein. There seems to be a certain degree of bias in the
      composition of order-promoting amino acids in the case of amyloidogenic proteins.
      Based on these parameters, a prediction function for the amyloidogenic propensity
      of proteins has been created. The prediction function has been found to
      rationalize the reported effect of certain mutations on amyloid formation. It
      seems that a higher sheet propensity of residues that constitute the first seven
      residues of a helical structure in a protein might increase the propensity for a
      helix to sheet transition in that region under denaturing conditions.

PMID- 15849217
TI  - An intein-based genetic selection allows the construction of a high-quality
      library of binary patterned de novo protein sequences.
AB  - Combinatorial libraries of synthetic DNA are increasingly being used to identify
      and evolve proteins with novel folds and functions. An effective strategy for
      maximizing the diversity of these libraries relies on the assembly of large genes
      from smaller fragments of synthetic DNA. To optimize library assembly and
      screening, it is desirable to remove from the synthetic libraries any sequences
      that contain unintended frameshifts or stop codons. Although genetic selection
      systems can be used to accomplish this task, the tendency of individual segments
      to yield misfolded or aggregated products can decrease the effectiveness of these
      selections. Furthermore, individual protein domains may misfold when removed from
      their native context. We report the development and characterization of an in
      vivo system to preselect sequences that encode uninterrupted gene segments
      regardless of the foldedness of the encoded polypeptide. In this system, the
      inserted synthetic gene segment is separated from an intein/thymidylate synthase
      (TS) reporter domain by a polyasparagine linker, thereby permitting the TS
      reporter to fold and function independently of the folding and function of the
      segment-encoded polypeptide. TS-deficient Escherichia coli host cells survive on
      selective medium only if the insert is uninterrupted and in-frame, thereby
      allowing selection and amplification of desired sequences. We demonstrate that
      this system can be used as a highly effective preselection tool for the
      production of large, diverse and high-quality libraries of de novo protein
      sequences.

PMID- 15849218
TI  - Anxiety, depression, and quality of life in caregivers of patients with cancer in
      late palliative phase.
AB  - BACKGROUND: Limited research has been done on mental health and health-related
      quality of life (QOL) of primary caregivers (PCs) to patients staying at home
      with advanced cancer. This study examines anxiety, depression, and QOL in PCs of
      patients with cancer in the late palliative phase. PATIENTS AND METHODS: The
      sample consisted of 49 PCs of women with breast cancer and 47 PCs of men with
      prostate cancer. QOL was rated with the Medical Outcome Study Short Form (SF-36),
      and mental health with the Hospital Anxiety and Depression Scale (HADS). The
      findings were compared with age-adjusted norm data (norm). RESULTS: Physical QOL
      was significantly higher than norm in both genders, while mental QOL was
      significantly lower in male PCs. The level of anxiety was significantly higher
      than norm in both genders. No significant difference for level of depression was
      found in either gender, while caseness of HADS-defined depression was
      significantly more prevalent in female PCs compared with norm. CONCLUSION: PCs of
      both genders had significantly more anxiety than norm samples. Health care
      personnel in contact with PCs should consider screening them for mental symptoms
      and QOL and, if necessary, recommend further evaluation by their doctors.

PMID- 15849219
TI  - Phase I trial of liposomal encapsulated doxorubicin (Myocet; D-99) and weekly
      docetaxel in advanced breast cancer patients.
AB  - BACKGROUND: We conducted a phase I trial to determine the safety and maximum
      tolerated dose (MTD) of non-pegylated liposome-encapsulated doxorubicin (Myocet;
      D-99) administered with weekly docetaxel in metastatic breast cancer (MBC)
      patients. PATIENTS AND METHODS: Twenty-one patients with no prior chemotherapy
      for MBC received D-99 (60 or 50 mg/m2) intravenously (i.v.) on day 1 and
      escalating doses of docetaxel (25, 30 and 35 mg/m2 i.v. on days 1 and 8 in
      cohorts of three to six patients. Treatment cycles were repeated every 21 days
      for a maximum of six cycles. RESULTS: The maximum tolerated dose (MTD) was 50
      mg/m2 of D-99 in combination with 25 mg/m2 of weekly docetaxel. The most common
      grade 4 toxicity was neutropenia that occurred in 42 (41%) of treatment cycles,
      with 10 hospitalizations for febrile neutropenia. Serious protocol-defined
      cardiac events occurred in three (14%) patients, with two (10%; 95% confidence
      interval [CI] 1% to 30%) developing congestive heart failure (CHF) after a total
      cumulative anthracycline dose (adjuvant doxorubicin + D-99) of 540 mg/m2.
      CONCLUSIONS: D-99 in combination with weekly docetaxel, at the doses and schedule
      as administered in this trial, is not recommended for phase II testing.
      Additional trials, using different doses and schedules, are required to evaluate
      the potential side-effects and efficacy of D-99 and docetaxel.

PMID- 15849220
TI  - Jaw avascular bone necrosis associated with long-term use of biphosphonates.

PMID- 15849221
TI  - Long-term survival of cancer patients in Germany achieved by the beginning of the
      third millenium.
AB  - BACKGROUND: Over the last decades, long-term survival rates have substantially
      increased for many forms of cancer. However, these improvements have often been
      detected with substantial delay by traditional methods of survival analyses.
      PATIENTS AND METHODS: Using data of the population-based Saarland Cancer
      Registry, 5- and 10-year relative survival rates were derived for patients with
      24 common forms of cancer in Saarland/Germany for the years 2000-2002 by period
      analysis and compared with conventional cohort estimates of 5- and 10-year
      relative survival rates pertaining to patients diagnosed in 1990-1992. RESULTS:
      For many forms of cancer, the 2000-2002 period survival estimates were
      substantially higher than the corresponding estimates for the cohorts of patients
      diagnosed in 1990-1992. For example, 10-year relative survival rates achieved in
      2000-2002 were close to 100% for patients with testis and thyroid cancer, >85%
      for patients with melanomas of the skin, approximately 80% for patients with
      endometrial cancer and prostate cancer, close to 70% for patients with breast
      cancer and kidney cancer, and close to 60% for patients with colon cancer and
      lymphomas. CONCLUSIONS: Survival expectations of patients diagnosed with cancer
      at the beginning of the third millenium are substantially higher than previously
      available survival statistics have suggested.

PMID- 15849222
TI  - A monoclonal antibody against HER-2 (trastuzumab) for metastatic breast cancer: a
      model-based cost-effectiveness analysis.
AB  - BACKGROUND: The aim of this study was to evaluate the cost-effectiveness of
      trastuzumab in patients with metastatic breast cancer (MBC) in a model-based cost
      effectiveness analysis (CEA). Trastuzumab has shown considerable activity in
      patients with MBC that overexpress HER2. However, significant resources have been
      allocated to finance this new therapy. Due to ever increasing pressures on health
      care budgets, economic evaluations are requested in order to compare health
      effects with costs. METHODS: All available data on trastuzumab in MBC presented
      at the San Antonio breast cancer conference in late 2003 and all data on Medline
      in December 2003 were analysed for life years (LY) gained and quality of life
      (QoL) with regard to the use of this new monoclonal antibody. Randomised studies
      comparing standard chemotherapy, with or without trastuzumab, were focused. The
      costs were calculated according to Norwegian prices as of January 2003. RESULTS:
      The LY gained ranged between 0.3 and 0.7 years. The median cost per patient
      treated was 44 196 yielding costs per life year saved in the range 63 137-162 417
      depending on survival gain and discount rate employed. A sensitivity analysis
      documented the price of trastuzumab and the survival benefit the two major
      factors influencing the cost-effectiveness ratio. CONCLUSION: The economic
      evaluation indicates that trastuzumab is not cost effective in metastatic breast
      cancer. Reduced drug costs and/or improved survival may alter the conclusion.

PMID- 15849223
TI  - Feasibility of high-dose interleukin-2 in heavily pretreated pediatric cancer
      patients.
AB  - BACKGROUND: The administration of high-dose interleukin-2 (IL-2) seems to be a
      therapeutic option for children with refractory and metastatic solid
      malignancies. METHODS: We prospectively studied treatment-related toxicities,
      quality of life and laboratory parameters in 10 children with progressive or
      metastatic solid tumors (metastatic osteosarcoma, n=4; neuroblastoma stage IV,
      n=3; metastatic Ewing's sarcoma, n=2; metastatic Wilms' tumor, n=1) during IL-2
      therapy. Patients were scheduled to receive five cycles of high-dose IL-2 by
      continuous infusion for 5 days every 3 weeks. RESULTS: All patients developed
      fever >39 degrees C and influenza-like symptoms, with a significant decrease in
      Karnofsky score. In two patients treatment had to be stopped after three cycles
      because of severe side-effects. During IL-2 therapy a statistical significant
      increase in white blood cells (WBC), creatinine, gamma-glutamyltransferase, C
      reactive protein, glucose and body weight was observed. In contrast, red blood
      cells, platelets, protein, albumin and cholinesterase significantly decreased.
      When results from day 1 of the first and of the fifth cycle were compared, an
      increase of WBC and a decrease of alkaline phosphatase was shown. No constant
      quantitative changes in total lymphocytes and subsets were observed during IL-2
      therapy. CONCLUSIONS: IL-2 treatment in children with refractory and relapsed
      solid malignancies is associated with severe, but reversible, side-effects.
      However, five of the 10 patients with diseases of worst prognosis could be
      rescued by this treatment.

PMID- 15849224
TI  - High activity and reduced neurotoxicity of bi-fractionated oxaliplatin plus 5
      fluorouracil/leucovorin for elderly patients with advanced colorectal cancer.
AB  - BACKGROUND: The proportion of elderly within the general population is increasing
      and the incidence of colorectal cancer increases with age. Oxaliplatin and 5
      fluorouracil (FU) combination is active in this disease. PATIENTS AND METHODS:
      This multicenter phase II study was designed to investigate feasibility,
      efficacy, activity of daily living (ADL) and instrumental activity of daily
      living (IADL) in elderly patients with metastatic colorectal cancer treated, as
      first-line chemotherapy, with a bi-fractionated oxaliplatin/5-FU based regimen.
      Treatment was oxaliplatin 45 mg/m2, leucovorin 200 mg/m2, 5-FU 400 mg/m2 and 22 h
      continuous infusion of 5-FU 600 mg/m2, all given intravenously on days 1 and 2,
      every 2 weeks. RESULTS: Seventy-eight patients were enrolled; median age was 75
      years (range 70-85). Among 77 evaluable patients, we observed seven complete
      responses and 32 partial responses, for an overall response rate of 51% (95%
      confidence interval 40% to 62%). A stabilization of disease was observed in 25%
      of patients while 19 patients progressed. Canadian NCI grade 3/4 toxicities were:
      neutropenia in 32% of patients (febrile in two), diarrhea in 10%, mucositis in
      4%, and fatigue in 4%. Sensory neuropathy was mild and occurred as grade 3 in 6%
      of patients. ADL and IADL scores did not change significantly during treatment.
      CONCLUSIONS: The bi-fractionated delivery of oxaliplatin plus 5-FU/leucovorin
      demonstrated high antitumor activity in elderly patients with advanced colorectal
      cancer. Splitting oxaliplatin administration might reduce incidence of severe
      neuropathy, although this has to be confirmed by further studies.

PMID- 15849225
TI  - Caffeine intake, CYP1A2 polymorphism and the risk of recurrent pregnancy loss.
AB  - Some case-control studies have demonstrated that caffeine intake and high CYP1A2
      activity increase risks of recurrent pregnancy loss (RPL) but the multifactorial
      effect is obscure. To investigate whether susceptible women who have more
      caffeine intake are at high risk of RPL, a case-control study of 58 cases with
      two or more RPL and fertile 147 controls was performed. The association between
      daily caffeine intake together with CYP1A21F (AA versus CA and CC) genotype and
      RPL was assessed. Without consideration of the genotype, there were no
      significant differences of the RPL risk in proportion to daily caffeine intake
      [less than 100 mg (reference); 100-299 mg: odds ratio (OR), 1.29; 95% confidence
      interval (CI), 0.66-2.50; 300 mg or more: OR, 1.82; 95% CI, 0.72-4.58; P for
      trend, 0.20]. However, the RPL risk significantly increased only among women who
      had homozygous CYP1A21F alleles with a dosage effect of daily caffeine intake
      [less than 100 mg (reference); 100-299 mg: OR, 1.94; 95% CI, 0.57-6.66; 300 mg or
      more: OR, 5.23; 95% CI, 1.05-25.9; P for trend, 0.03]. It was demonstrated for
      the first time that an increase in caffeine intake deteriorates the fecundity
      among susceptible women.

PMID- 15849226
TI  - Meiotic studies in an azoospermic human translocation (Y;1) carrier.
AB  - A reciprocal translocation between the long arm of the Y chromosome and the long
      arm of chromosome 1 was observed in an infertile man with non-obstructive
      azoospermia. The study was performed using a combination of techniques:
      immunocytogenetic analysis, which allows the detection of synaptonemal complexes
      (SCs) and recombination sites (MLH1) simultaneously, and fluorescence in-situ
      hybridization analysis. Meiotic pairing analysis on 100 pachytene spreads showed
      the presence of a quadrivalent containing chromosomes 1 and Y. There were many
      abnormalities in chromosome pairing and recombination. These abnormalities
      included a great reduction of recombination events (as many as one fifth of the
      SCs had no MLH1 foci), and high proportions of unpaired regions and
      discontinuities in the SCs. We discuss the possibility that infertility in this
      patient may be due to transcriptional repression of part of chromosome 1 involved
      in the translocation, silencing some genes necessary for the progression of
      meiosis and causing defective meiotic pairing and recombination.

PMID- 15849227
TI  - Cellular expression of protamine 1 and 2 transcripts in testicular spermatids
      from azoospermic men submitted to TESE-ICSI.
AB  - Testicular sperm extraction (TESE) combined with ICSI is used to treat
      azoospermia. However, the factors that influence the outcome of ICSI in this
      situation are ill-defined. We sought to investigate the expression of protamine 1
      (PRM1) and protamine 2 (PRM2) transcripts in testicular spermatids from
      obstructive and non-obstructive azoospermic men with impaired spermatogenesis.
      The relationship between PRM1 and PRM2 transcript levels and the TESE-ICSI
      outcome was evaluated. The cellular expression of PRM1 and PRM2 mRNAs in single
      testicular spermatids from 41 azoospermic patients (in whom testicular
      spermatozoa were subsequently recovered and submitted for TESE-ICSI) was
      determined by radioactive in situ hybridization. Group I contained seven men with
      congenital, obstructive azoospermia and whose testicular biopsies indicated
      quantitatively normal spermatogenesis. Group II consisted of 18 azoospermic men
      with moderately impaired spermatogenesis. Sixteen men with non-obstructive
      azoospermia and severely deranged spermatogenesis (i.e. mixed atrophy with small
      foci of spermatids and spermatozoa) constituted group III. The spermatids of men
      with severely deranged spermatogenesis exhibited significant lower PRM1 mRNA
      expression than in the other patient groups. There were no significant inter
      group differences in PRM2 mRNA expression. Spermatid PRM1 expression was lower in
      non-pregnant couples than in pregnant couples. The low number of spermatids in
      cases of mixed atrophy with small spermatogenic foci is associated with
      significantly lower PRM1 expression and a lower pregnancy rate. These results
      emphasize the role of PRM1 as a potentially critical factor in post-ICSI
      embryonic development.

PMID- 15849228
TI  - Detrimental effects after dobutamine infusion on rat left ventricular function:
      mechanical work and energetics.
AB  - We have previously reported that continuous infusion of dobutamine into the
      coronary artery induces positive inotropic effects but induces no detrimental
      effects in cross-circulated, excised normal rat hearts and even in Ca2+ overload
      induced contractile failing rat hearts. However, we hypothesized that some
      detrimental effects on left ventricular (LV) function are induced after
      continuous dobutamine infusion and the following clearance of blood dobutamine,
      as is the case after beta-adrenergic receptor stimulation. To test this
      hypothesis, we investigated LV mechanical work and energetics in the same type of
      preparations that underwent continuous dobutamine infusion and clearance of blood
      dobutamine. We found that both mean end-systolic pressure and systolic pressure
      volume area (PVA; a measure of total mechanical energy per beat) at midrange LV
      volume were significantly (P < 0.01) decreased. The mean myocardial oxygen
      consumption per beat intercept, which is composed of for the total Ca2+ handling
      in excitation-contraction coupling and basal metabolism, of the and PVA linear
      relation was also significantly (P < 0.05) decreased (n=8). The mean slope of the
      linear relation was unchanged in such hearts. Post-dobutamine basal metabolism
      was unchanged (n = 5 of the 8 hearts). The moderate proteolysis of a cytoskeleton
      protein, alpha-fodrin was identified (n = 7 of the 8 hearts with the decreased
      intercept), after clearance of blood dobutamine. In agreement with our
      hypothesis, the detrimental effect of the post-beta-adrenergic receptor
      stimulation was induced by a moderate concentration of dobutamine; we found
      systolic dysfunction due to the impairment of Ca2+ handling in excitation
      contraction coupling in the rat LV and proteolysis of a cytoskeleton protein,
      alpha-fodrin.

PMID- 15849229
TI  - Effect of acute body positional changes on the haemodynamics of rats with and
      without myocardial infarction.
AB  - In humans, the lateral recumbent position has a beneficial effect on
      haemodynamics. If this effect is substantial in small animals too, there is a
      risk of misinterpretation in preclinical investigations. Therefore, the aim of
      this study was to analyse the impact of acute changes in body position on
      haemodynamics in rats. Healthy rats (n=21) and rats post myocardial infarction
      (n=20) were randomly positioned supine, prone, or on the right or left side. In
      each position, we measured haemodynamic parameters by pressure-tip catheter and
      thermodilution. We found that left ventricular contractility (dP/dtmax) was
      significantly elevated in both lateral positions as compared to the supine
      position in healthy rats. In healthy rats and following infarction, cardiac index
      (CI) and stroke volume index (SVI) were significantly higher in both lateral
      positions as compared to the supine or prone position. Of importance, if SVI
      values in the supine position in healthy rats (0.095 +/- 0.003 ml (100 g)(-1))
      are compared to SVI values measured in different positions after myocardial
      infarction, the SVI can be either significantly lower in the supine (0.084 +/-
      0.003 ml (100 g)(-1)) or significantly higher in the left lateral position (0.105
      +/- 0.003 ml (100 g)(-1)). We conclude that post myocardial infarction and in
      healthy control rats, important haemodynamic values are increased in lateral
      positions as compared to prone or supine positions. Analysing haemodynamic data
      in rats may therefore result in misinterpretation if the body position is
      inconsistent.

PMID- 15849230
TI  - Effect of whole body resistance training on arterial compliance in young men.
AB  - The effect of resistance training on arterial stiffening is controversial. We
      tested the hypothesis that resistance training would not alter central arterial
      compliance. Young healthy men (age, 23 +/- 3.9 (mean +/- s.e.m.) years; n = 28,)
      were whole-body resistance trained five times a week for 12 weeks, using a
      rotating 3-day split-body routine. Resting brachial blood pressure (BP), carotid
      pulse pressure, carotid cross-sectional compliance (CSC), carotid initima-media
      thickness (IMT) and left ventricular dimensions were evaluated before beginning
      exercise (PRE), after 6 weeks of exercise (MID) and at the end of 12 weeks of
      exercise (POST). CSC was measured using the pressure-sonography method. Results
      indicate reductions in brachial (61.1 +/- 1.4 versus 57.6 +/- 1.2 mmHg; P < 0.01)
      and carotid pulse pressure (52.2 +/- 1.9 versus 46.8 +/- 2.0 mmHg; P < 0.01) PRE
      to POST. In contrast, carotid CSC, beta-stiffness index, IMT and cardiac
      dimensions were unchanged. In young men, central arterial compliance is unaltered
      with 12 weeks of resistance training and the mechanisms responsible for cardiac
      hypertrophy and reduced arterial compliance are either not inherent to all
      resistance-training programmes or may require a prolonged stimulus.

PMID- 15849231
TI  - Selective impairment of hand mental rotation in patients with focal hand
      dystonia.

PMID- 15849232
TI  - Transport of extracellular l-arginine via cationic amino acid transporter is
      required during in vivo endothelial nitric oxide production.
AB  - In cultured endothelial cells, 70-95% of extracellular l-arginine uptake has been
      attributed to the cationic amino acid transporter-1 protein (CAT-1). We tested
      the hypothesis that extracellular l-arginine entry into endothelial cells via CAT
      1 plays a crucial role in endothelial nitric oxide (NO) production during in vivo
      conditions. Using l-lysine, the preferred amino acid transported by CAT-1, we
      competitively inhibited extracellular l-arginine transport into endothelial cells
      during conditions of NaCl hyperosmolarity, low oxygen, and flow increase. Our
      prior studies indicate that each of these perturbations causes NO-dependent
      vasodilation. The perivascular NO concentration ([NO]) and blood flow were
      determined in the in vivo rat intestinal microvasculature. Suppression of
      extracellular l-arginine transport significantly and strongly inhibited increases
      in vascular [NO] and intestinal blood flow during NaCl hyperosmolarity, lowered
      oxygen tension, and increased flow. These results suggest that l-arginine from
      the extracellular space is accumulated by CAT-1. When CAT-1-mediated transport of
      extracellular l-arginine into endothelial cells was suppressed, the endothelial
      cell NO response to a wide range of physiological stimuli was strongly depressed.

PMID- 15849233
TI  - Interaction between left ventricular wall motion and intraventricular flow
      propagation in acute and chronic ischemia.
AB  - Myocardial ischemia has been associated with left ventricular (LV) postsystolic
      shortening. The combination of tissue Doppler imaging and high frame-rate
      acquisition of two-dimensional color flow makes it possible to study the
      interaction between LV wall motion and intraventricular flow propagation. The aim
      of this study was to examine in a clinical model the impact that acute myocardial
      ischemia and prior myocardial infarct might have on LV flow patterns and to
      explain the underlying mechanisms from the tissue Doppler data. LV flow
      propagation and tissue velocities during early diastole were studied in 18
      healthy individuals, 17 patients with prior anterior myocardial infarct, and 16
      patients before and during percutaneous coronary intervention (PCI) of the left
      anterior descending artery. Normal individuals had intraventricular flow
      propagation toward the apex during isovolumic relaxation. During this early
      diastolic time phase, myocardial velocities measured at mid- and apical septal
      segment were directed away from the apex. Before PCI, patients without myocardial
      infarction had similar findings as in normal individuals. In contrast, each
      patient with either prior myocardial infarction or PCI-induced acute ischemia had
      flow propagation opposite to normal individuals, and tissue velocities reversed
      toward the apex during early diastole. Reversal of early diastolic LV flow
      propagation in acute and chronic anterior myocardial ischemia reflects
      postsystolic shortening in the dyskinetic apical and septal myocardial segments.

PMID- 15849234
TI  - Substrate size as a determinant of fibrillatory activity maintenance in a
      mathematical model of canine atrium.
AB  - Tissue size has been considered an important determinant of atrial fibrillation
      (AF), but recent work has questioned the critical size hypothesis. Here, we use a
      previously developed mathematical model of the two-dimensional canine atrium with
      realistic action potential, ionic, and conduction properties to address substrate
      size effects on the maintenance of fibrillatory activity. Cholinergic AF was
      simulated at different acetylcholine (ACh) concentrations ([ACh]) and
      distributions, with substrate area varied 11.1-fold. Automated phase singularity
      detection was used to facilitate the analysis of arrhythmic activity. The
      duration of activity induced by a single extrastimulus increased with increasing
      substrate dimensions. Two general mechanisms underlying activity were observed
      and were differentially affected by substrate size. For large mean [ACh], single
      primary rotors anchored in low-[ACh] zones maintained activity and substrate
      dimensions were not critical. At lower mean [ACh], extensive spiral wave meander
      prevented the emergence of single stable rotors. Prolonged activity was favored
      when substrate size permitted a sufficiently large number of simultaneous longer
      lasting rotors that extinction of all was unlikely. Thus either single dominant
      rotor or multiple reentrant spiral generator mechanisms could maintain
      fibrillatory activity in this model and were differentially dependent on
      substrate size. These results speak to recent debates about the role in AF of
      single driver rotors versus multiple reentrant circuit mechanisms by suggesting
      that either may maintain fibrillatory atrial activity depending on atrial size
      and electrophysiological properties.

PMID- 15849235
TI  - Enhanced expression of fibrillin-1, a constituent of the myocardial extracellular
      matrix in fibrosis.
AB  - Fibrillin-1 localization in the myocardium and the modulation of its expression
      in cardiac fibrosis were examined. In normal rat hearts, fibrillin-1 was abundant
      throughout the myocardium as thin fibers that crossed over the perimysium and
      around arteries. After cardiac fibrosis was induced in rats by either 14-day ANG
      II infusion or 21-day DOCA-salt treatment [a high endothelin-1 (ET-1) model],
      fibrillin-1 immunostaining was stronger in the interstitium (2.8-fold and 4.4
      fold increases, respectively, in each model), extended between myocytes, and
      accumulated in microscopic scars and in the perivascular area of both ventricles.
      mRNA analysis confirmed its enhanced ventricular expression in both groups of
      rats (2.5-fold and 6.6-fold increments, respectively, in each model). In 1B
      normotensive and 2C hypertensive transgenic mice, two lines expressing an ANG II
      fusion protein in cardiac myocytes, strong fibrillin-1 immunoreactivity was
      observed in the interstitium and around arteries (3.7-fold and 7-fold increases,
      respectively). ANG II and transforming growth factor-beta1 enhanced fibrillin-1
      synthesis by cardiac fibroblasts. Some fibrillin-1 fragments interacted with RGD
      dependent integrins, including alpha(8)beta(1)-integrin, of cardiac fibroblasts
      but not necessarily through the RGD motif. Our findings illustrate that fibrillin
      1 is an important constituent of the myocardium. In vitro and in vivo evidence
      suggests that ANG II can directly induce fibrillin-1 expression in cardiac
      fibroblasts. This protein can thus contribute to reactive and reparative
      processes.

PMID- 15849236
TI  - Adrenergic catecholamine trophic activity contributes to flow-mediated arterial
      remodeling.
AB  - Stimulation of alpha1-adrenoceptors (ARs) induces proliferation, hypertrophy, and
      migration of vascular smooth muscle cells and adventitial fibroblasts in cell and
      organ culture. In vivo studies have confirmed this direct trophic action and
      found that endogenous catecholamines contribute to neointimal formation and wall
      hypertrophy induced by mechanical injury. In murine carotid artery, these effects
      are mediated by alpha 1B-ARs, whereas alpha 1D-ARs mediate contraction and alpha
      1A-ARs are not expressed. Herein, we examined whether catecholamines also
      contribute to arterial wall growth in a noninjury model, i.e., flow-mediated
      remodeling. In wild-type mice or mice deficient in norepinephrine and epinephrine
      synthesis [dopamine beta-hydroxylase knockout (DBH-KO)], all distal branches of
      the left carotid artery (LC) except the thyroid artery were ligated to reduce
      flow in the LC and increase flow in the right carotid artery (RC). Twenty-one
      days later, negative hypertrophic remodeling of the LC [i.e., -20% (decrease) in
      lumen area, -2% in circumference of the external elastic lamina (CEEL), +98%
      (increase) in thickness of the intima media, and +71% in thickness for
      adventitia; P < 0.01 vs. sham ligation] and positive eutrophic remodeling of the
      RC [+23% in lumen area, +11% in CEEL; P < 0.01 vs. sham ligation] were inhibited
      in DBH-KO mice [LC: +10% intima media and +3% adventitia; RC: +9% lumen area and
      +3% CEEL]. This inhibition was associated with reduced proliferation in the RC
      and reduced apoptosis and leukocyte accumulation in the RC and LC when examined 5
      days after ligation. Carotid remodeling in alpha 1D-AR-knockout mice evidenced
      little or no inhibition, which suggests dependence on alpha 1B-ARs. These
      findings suggest that catecholamine-induced trophic activity contributes to both
      flow-mediated negative remodeling and adaptive positive arterial remodeling.

PMID- 15849237
TI  - Abnormal cardiac inflow patterns during postnatal development in a mouse model of
      Holt-Oram syndrome.
AB  - Tbx5(del/+) mice provide a model of human Holt-Oram syndrome. In this study, the
      cardiac functional phenotypes of this mouse model were investigated with 30-MHz
      ultrasound by comparing 12 Tbx5(del/+) mice with 12 wild-type littermates at 1,
      2, 4, and 8 wk of age. Cardiac dimensions were measured with two-dimensional and
      M-mode imaging. The flow patterns in the left and right ventricular inflow
      channels were evaluated with Doppler flow sampling. Compared with wild-type
      littermates, Tbx5(del/+) mice showed significant changes in the mitral flow
      pattern, including decreased peak velocity of the left ventricular (LV) early
      filling wave (E wave), increased peak velocity of the late filling wave (A wave),
      and decreased or even reversed peak E-to-A ratio. The prolongation of LV
      isovolumic relaxation time was detected in Tbx5(del/+) neonates as early as 1 wk
      of age. In Tbx5(del/+) mice, LV wall thickness appeared normal but LV chamber
      dimension was significantly reduced. LV systolic function did not differ from
      that in wild-type littermates. In contrast, the Doppler flow spectrum in the
      enlarged tricuspid orifice of Tbx5(del/+) mice demonstrated increased peak
      velocities of both E and A waves and increased total time-velocity integral but
      unchanged peak E/A. In another 13 mice (7 Tbx5(del/+), 6 wild-type) at 2 wk of
      age, significant correlation was found between Tbx5 gene expression level in
      ventricular myocardium and LV filling parameters. In conclusion, the LV diastolic
      function of Tbx5(del/+) mice is significantly deteriorated, whereas the systolic
      function remains normal.

PMID- 15849238
TI  - Second harmonic imaging of exocytosis at fertilization.
AB  - Second harmonic generation offers an important alternative and complement to
      fluorescence for the imaging of cellular structure and function. Staining the
      eggs of the sea urchin, Lytechinus pictus, with the styryl dye di-8-ANEPPS, we
      have observed large changes in both second harmonic generation and two-photon
      fluorescence after fertilization, consistent with the dynamics of exocytosis of
      cortical granules. With nonlinear imaging on a scanning microscope, we are able
      to visualize the wave of exocytosis in real time.

PMID- 15849239
TI  - Glioma expansion in collagen I matrices: analyzing collagen concentration
      dependent growth and motility patterns.
AB  - We study the growth and invasion of glioblastoma multiforme (GBM) in three
      dimensional collagen I matrices of varying collagen concentration. Phase-contrast
      microscopy studies of the entire GBM system show that invasiveness at early times
      is limited by available collagen fibers. At early times, high collagen
      concentration correlates with more effective invasion. Conversely, high collagen
      concentration correlates with inhibition in the growth of the central portion of
      GBM, the multicellular tumor spheroid. Analysis of confocal reflectance images of
      the collagen matrices quantifies how the collagen matrices differ as a function
      of concentration. Studying invasion on the length scale of individual invading
      cells with a combination of confocal and coherent anti-Stokes Raman scattering
      microscopy reveals that the invasive GBM cells rely heavily on cell-matrix
      interactions during invasion and remodeling.

PMID- 15849240
TI  - The effect of branching on the critical concentration and average filament length
      of actin.
AB  - The dependences of the steady-state critical concentration and average filament
      length of actin solutions, on the filament branching and capping rates, are
      calculated using a rate methodology based on the total number of actin filaments.
      The methodology generalizes calculations of the "treadmilling" actin
      concentration at which an average filament has net zero growth rate. The
      predictions of the rate methodology are validated by comparison with stochastic
      growth simulations that track the positions of all filament subunits over time.
      For side branching, the critical concentration drops proportionally to the square
      root of the branching rate; for end branching the drop is linear. The
      polymerization response to branching has a maximum as a function of the capping
      protein concentration. The average filament length drops with increasing
      branching, because the critical concentration drops. Even small rates of filament
      uncapping have a large impact on the average filament length in vitro. The
      potential significance of these phenomena for cell behavior is evaluated.

PMID- 15849241
TI  - Kinetic stability of intermolecular DNA quadruplexes.
AB  - Fluorescently labeled oligodeoxyribonucleotides containing a single tract of four
      successive guanines have been used to study the thermodynamic and kinetic
      properties of short intermolecular DNA quadruplexes. When these assemble to form
      intermolecular quadruplexes the fluorophores are in close proximity and the
      fluorescence is quenched. On raising the temperature these complexes dissociate
      and there is a large increase in fluorescence. These complexes are exceptionally
      stable in potassium-containing buffers, and possess Tm values that are too high
      to measure. Tm values were determined in sodium-containing buffers for which the
      rate of reannealing is extremely slow; the melting profiles are effectively
      irreversible, and the apparent melting temperatures are dependent on the rates of
      heating. The dissociation kinetics of these complexes was estimated by rapidly
      increasing the temperature and following the time-dependent changes in
      fluorescence. From these data we have estimated the half-lives of these
      quadruplexes at 37 degrees C. Addition of a T to the unlabeled end of the
      oligonucleotide increases quadruplex stability. In contrast, addition of a T
      between the fluorophore and the oligonucleotide leads to a decrease in stability.

PMID- 15849242
TI  - Rapid substrate-induced charge movements of the GABA transporter GAT1.
AB  - The GABA transporter GAT1 removes the neurotransmitter GABA from the synaptic
      cleft by coupling of GABA uptake to the co-transport of two sodium ions and one
      chloride ion. The aim of this work was to investigate the individual reaction
      steps of GAT1 after a GABA concentration jump. GAT1 was transiently expressed in
      HEK293 cells and its pre-steady-state kinetics were studied by combining the
      patch-clamp technique with the laser-pulse photolysis of caged GABA, which
      allowed us to generate GABA concentration jumps within <100 micros. Recordings of
      transport currents generated by GAT1, both in forward and exchange transport
      modes, showed multiple charge movements that can be separated along the time
      axis. The individual reactions associated with these charge movements differ from
      the well-characterized electrogenic "sodium-occlusion" reaction by GAT1. One of
      the observed electrogenic reactions is shown to be associated with the GABA
      translocating half-cycle of the transporter, in contradiction to previous studies
      that showed no charge movements associated with these reactions. Interestingly,
      reactions of the GABA-bound transporter were not affected by the absence of
      extracellular chloride, suggesting that Cl- may not be co-translocated with GABA.
      Based on the results, a new alternating access sequential-binding model is
      proposed for GAT1's transport cycle that describes the results presented here and
      those by others.

PMID- 15849243
TI  - Rapid analysis of Forster resonance energy transfer by two-color global
      fluorescence correlation spectroscopy: trypsin proteinase reaction.
AB  - In this study we introduce the combination of two-color global fluorescence
      correlation spectroscopy (2CG-FCS) and Forster resonance energy transfer (FRET)
      as a very powerful combination for monitoring biochemical reactions on the basis
      of single molecule events. 2CG-FCS, which is a new variation emerging from the
      family of fluorescence correlation spectroscopy, globally analyzes the
      simultaneously recorded auto- and cross-correlation data from two photon
      detectors monitoring the fluorescence emission of different colors. Overcoming
      the limitations inherent in mere auto- and cross-correlation analysis, 2CG-FCS is
      sensitive in resolving and quantifying fluorescent species that differ in their
      diffusion characteristics and/or their molecular brightness either in one or both
      detection channels. It is able to account for effects that have often been
      considered as sources of severe artifacts in two-color and FRET measurements, the
      most prominent artifacts comprising photobleaching, cross talk, or concentration
      variations in sample preparation. Because of its very high statistical accuracy,
      the combination of FRET and 2CG-FCS is suited for high-throughput applications
      such as drug screening. Employing beam scanning during data acquisition even
      further enhances this capability and allows measurement times of <2 s. The
      improved performance in monitoring a FRET sample was verified by following the
      protease cleavage reaction of a FRET-active peptide. The FRET-inactive
      subpopulation of uncleaved substrate could be correctly assigned, revealing a
      substantial portion of inactive or missing acceptor label. The results were
      compared to those obtained by two-dimensional fluorescence intensity distribution
      analysis.

PMID- 15849244
TI  - Relating surfactant properties to activity and solubilization of the human
      adenosine a3 receptor.
AB  - The effects of various surfactants on the activity and stability of the human
      adenosine A3 receptor (A3) were investigated. The receptor was expressed using
      stably transfected HEK293 cells at a concentration of 44 pmol functional receptor
      per milligram membrane protein and purified using over 50 different nonionic
      surfactants. A strong correlation was observed between a surfactant's ability to
      remove A3 from the membrane and the ability of the surfactant to remove A3
      selectively relative to other membrane proteins. The activity of A3 once purified
      also correlates well with the selectivity of the surfactant used. The effects of
      varying the surfactant were much stronger than those achieved by including A3
      ligands in the purification scheme. Notably, all surfactants that gave high
      efficiency, selectivity and activity fall within a narrow range of hydrophile
      lipophile balance values. This effect may reflect the ability of the surfactant
      to pack effectively at the hydrophobic transmembrane interface. These findings
      emphasize the importance of identifying appropriate surfactants for a particular
      membrane protein, and offer promise for the development of rapid, efficient, and
      systematic methods to facilitate membrane protein purification.

PMID- 15849245
TI  - Theory of force regulation by nascent adhesion sites.
AB  - The mechanical coupling of a cell with the extracellular matrix relies on
      adhesion sites, clusters of membrane-associated proteins that communicate forces
      generated along the F-Actin filaments of the cytoskeleton to connecting tissue.
      Nascent adhesion sites have been shown to regulate these forces in response to
      tissue rigidity. Force-regulation by substrate rigidity of adhesion sites with
      fixed area is not possible for stationary adhesion sites, according to elasticity
      theory. A simple model is presented to describe force regulation by dynamical
      adhesion sites.

PMID- 15849246
TI  - Interaction of human apolipoprotein A-I with model membranes exhibiting lipid
      domains.
AB  - Several mechanisms for cell cholesterol efflux have been proposed, including
      membrane microsolubilization, suggesting that the existence of specific domains
      could enhance the transfer of lipids to apolipoproteins. In this work isothermal
      titration calorimetry, circular dichroism spectroscopy, and two-photon microscopy
      are used to study the interaction of lipid-free apolipoprotein A-I (apoA-I) with
      small unilamellar vesicles (SUVs) of 1-palmitoyl, 2-oleoyl phosphatidylcholine
      (POPC) and sphingomyelin (SM), with and without cholesterol. Below 30 degrees C
      the calorimetric results show that apoA-I interaction with POPC/SM SUVs produces
      an exothermic reaction, characterized as nonclassical hydrophobic binding. The
      heat capacity change (DeltaCp degrees ) is small and positive, whereas it was
      larger and negative for pure POPC bilayers, in the absence of SM. Inclusion of
      cholesterol in the membranes induces changes in the observed thermodynamic
      pattern of binding and counteracts the formation of alpha-helices in the protein.
      Above 30 degrees C the reactions are endothermic. Giant unilamellar vesicles
      (GUVs) of identical composition to the SUVs, and two-photon fluorescence
      microscopy techniques, were utilized to further characterize the interaction.
      Fluorescence imaging of the GUVs indicates coexistence of lipid domains under 30
      degrees C. Binding experiments and Laurdan generalized-polarization measurements
      suggest that there is no preferential binding of the labeled apoA-I to any
      particular domain. Changes in the content of alpha-helix, binding, and fluidity
      data are discussed in the framework of the thermodynamic parameters.

PMID- 15849247
TI  - Multiple loops of the dihydropyridine receptor pore subunit are required for full
      scale excitation-contraction coupling in skeletal muscle.
AB  - Understanding which cytosolic domains of the dihydropyridine receptor participate
      in excitation-contraction (EC) coupling is critical to validate current
      structural models. Here we quantified the contribution to skeletal-type EC
      coupling of the alpha1S (CaV1.1) II-III loop when alone or in combination with
      the rest of the cytosolic domains of alpha1S. Chimeras consisting of alpha1C
      (CaV1.2) with alpha1S substitutions at each of the interrepeat loops (I-II, II
      III, and III-IV loops) and N- and C-terminal domains were evaluated in dysgenic
      (alpha1S-null) myotubes for phenotypic expression of skeletal-type EC coupling.
      Myotubes were voltage-clamped, and Ca2+ transients were measured by confocal line
      scan imaging of fluo-4 fluorescence. In agreement with previous results, the
      alpha1C/alpha1S II-III loop chimera, but none of the other single-loop chimeras,
      recovered a sigmoidal fluorescence-voltage curve indicative of skeletal-type EC
      coupling. To quantify Ca2+ transients in the absence of inward Ca2+ current, but
      without changing the external solution, a mutation, E736K, was introduced into
      the P-loop of repeat II of alpha1C. The Ca2+ transients expressed by the
      alpha1C(E736K)/alpha1S II-III loop chimera were approximately 70% smaller than
      those expressed by the Ca2+-conducting alpha1C/alpha1S II-III variant. The low
      skeletal-type EC coupling expressed by the alpha1C/alpha1S II-III loop chimera
      was confirmed in the Ca2+-conducting alpha1C/alpha1S II-III loop variant using
      Cd2+ (10(-4) M) as the Ca2+ current blocker. In contrast to the behavior of the
      II-III loop chimera, Ca2+ transients expressed by an alpha1C/alpha1S chimera
      carrying all tested skeletal alpha1S domains (all alpha1S interrepeat loops, N-
      and C-terminus) were similar in shape and amplitude to wild-type alpha1S, and did
      not change in the presence of the E736K mutation or in the presence of 10(-4) M
      Cd2+. Controls indicated that similar dihydropyridine receptor charge movements
      were expressed by the non-Ca2+ permeant alpha1S(E1014K) variant, the
      alpha1C(E736K)/alpha1S II-III loop chimera, and the alpha1C(E736K)/alpha1S
      chimera carrying all tested alpha1S domains. The data indicate that the
      functional recovery produced by the alpha1S II-III loop is incomplete and that
      multiple cytosolic domains of alpha1S are necessary for a quantitative recovery
      of the EC-coupling phenotype of skeletal myotubes. Thus, despite the importance
      of the II-III loop there may be other critical determinants in alpha1S that
      influence the efficiency of EC coupling.

PMID- 15849248
TI  - Molecular dynamics simulation of sperm whale myoglobin: effects of mutations and
      trapped CO on the structure and dynamics of cavities.
AB  - The results of extended (80-ns) molecular dynamics simulations of wild-type and
      YQR triple mutant of sperm whale deoxy myoglobin in water are reported and
      compared with the results of the simulation of the intermediate(s) obtained by
      photodissociation of CO in the wild-type protein. The opening/closure of pathways
      between preexistent cavities is different in the three systems. For the
      photodissociated state, we previously reported a clear-cut correlation between
      the opening probability and the presence of the photolyzed CO in the proximity of
      the passage; here we show that in wild-type deoxy myoglobin, opening is almost
      random. In wild-type deoxy myoglobin, the passage between the distal pocket and
      the solvent is strictly correlated to the presence/absence of a water molecule
      that simultaneously interacts with the distal histidine side chain and the heme
      iron; conversely, in the photodissociated myoglobin, the connection with the bulk
      solvent is always open when CO is in the vicinity of the A pyrrole ring. In YQR
      deoxy myoglobin, the mutated Gln(E7)64 is stably H-bonded with the mutated
      Tyr(B10)29. The essential dynamics analysis unveils a different behavior for the
      three systems. The motion amplitude is progressively restricted in going from
      wild-type to YQR deoxy myoglobin and to wild-type myoglobin photoproduct. In all
      cases, the principal motions involve mainly the same regions, but their
      directions are different. Analysis of the dynamics of the preexisting cavities
      indicates large fluctuations and frequent connections with the solvent, in
      agreement with the earlier hypothesis that some of the ligand may escape from the
      protein through these pathways.

PMID- 15849249
TI  - A new muscle contractile system composed of a thick filament lattice and a single
      actin filament.
AB  - To bridge the gap between the contractile system in muscle and in vitro motility
      assay, we have devised an A-band motility assay system. A glycerinated skeletal
      myofibril was treated with gelsolin to selectively remove the thin filaments and
      expose a single A-band. A single bead-tailed actin filament trapped by optical
      tweezers was made to interact with the inside or the outer surface of the A-band,
      and the displacement of the bead-tailed filament was measured in a physiological
      ionic condition by phase-contrast and fluorescence microscopy. We observed large
      back-and-forth displacement of the filament accompanied by a large change in
      developed force. Despite this large tension fluctuation, we found that the
      average force was proportional to the overlap inside and outside the A-band up to
      approximately 150 nm and 300 nm from the end of the A-band, respectively.
      Consistent with the difference in the density of myosin molecules, the average
      force per unit length of the overlap inside the A-band (the time-averaged
      force/myosin head was approximately 1 pN) was approximately twice as large as
      that outside. Thus, we conclude that the A-band motility assay system described
      here is suitable for studying force generation on a single actin filament, and
      its sliding movement within a regular three-dimensional thick filament lattice.

PMID- 15849250
TI  - The dynamics and mechanics of endothelial cell spreading.
AB  - Cell adhesion to extracellular matrix is mediated by receptor-ligand
      interactions. When a cell first contacts a surface, it spreads, exerting traction
      forces against the surface and forming new bonds as its contact area expands.
      Here, we examined the changes in shape, actin polymerization, focal adhesion
      formation, and traction stress generation that accompany spreading of endothelial
      cells over a period of several hours. Bovine aortic endothelial cells were plated
      on polyacrylamide gels derivatized with a peptide containing the integrin binding
      sequence RGD, and changes in shape and traction force generation were measured.
      Notably, both the rate and extent of spreading increase with the density of
      substrate ligand. There are two prominent modes of spreading: at higher surface
      ligand densities cells tend to spread isotropically, whereas at lower densities
      of ligand the cells tend to spread anisotropically, by extending pseudopodia
      randomly distributed along the cell membrane. The extension of pseudopodia is
      followed by periods of growth in the cell body to interconnect these extensions.
      These cycles occur at very regular intervals and, furthermore, the extent of
      pseudopodial extension can be diminished by increasing the ligand density.
      Measurement of the traction forces exerted by the cell reveals that a cell is
      capable of exerting significant forces before either notable focal adhesion or
      stress fiber formation. Moreover, the total magnitude of force exerted by the
      cell is linearly related to the area of the cell during spreading. This study is
      the first to monitor the dynamic changes in the cell shape, spreading rate, and
      forces exerted during the early stages (first several hours) of endothelial cell
      adhesion.

PMID- 15849251
TI  - Inferring the diameter of a biopolymer from its stretching response.
AB  - We investigate the stretching response of a thick polymer model by means of
      extensive stochastic simulations. The computational results are synthesized in an
      analytic expression that characterizes how the force versus elongation curve
      depends on the polymer structural parameters: its thickness and granularity
      (spacing of the monomers). The expression is used to analyze experimental data
      for the stretching of various different types of biopolymers: polypeptides,
      polysaccharides, and nucleic acids. Besides recovering elastic parameters (such
      as the persistence length) that are consistent with those obtained from standard
      entropic models, the approach allows us to extract viable estimates for the
      polymers diameter and granularity. This shows that the basic structural polymer
      features have such a profound impact on the elastic behavior that they can be
      recovered with the sole input of stretching measurements.

PMID- 15849252
TI  - Hierarchical extensibility in the PEVK domain of skeletal-muscle titin.
AB  - Titin is the main determinant of passive muscle force. Physiological extension of
      titin derives largely from its PEVK (Pro-Glu-Val-Lys) domain, which has a
      different length in different muscle types. Here we characterized the elasticity
      of the full-length, human soleus PEVK domain by mechanically manipulating its
      contiguous, recombinant subdomain segments: an N-terminal (PEVKI), a middle
      (PEVKII), and a C-terminal (PEVKIII) one third. Measurement of the apparent
      persistence lengths revealed a hierarchical arrangement according to local
      flexibility: the N-terminal PEVKI is the most rigid and the C-terminal PEVKIII is
      the most flexible segment within the domain. Immunoelectron microscopy supported
      the hierarchical extensibility within the PEVK domain. The effective persistence
      lengths decreased as a function of ionic strength, as predicted by the Odijk
      Skolnick-Fixman model of polyelectrolyte chains. The ionic strength dependence of
      persistence length was similar in all segments, indicating that the residual
      differences in the elasticity of the segments derive from nonelectrostatic
      mechanisms.

PMID- 15849253
TI  - Gradient of rigidity in the lamellipodia of migrating cells revealed by atomic
      force microscopy.
AB  - Changes in mechanical properties of the cytoplasm have been implicated in cell
      motility, but there is little information about these properties in specific
      regions of the cell at specific stages of the cell migration process. Fish
      epidermal keratocytes with their stable shape and steady motion represent an
      ideal system to elucidate temporal and spatial dynamics of the mechanical state
      of the cytoplasm. As the shape of the cell does not change during motion and
      actin network in the lamellipodia is nearly stationary with respect to the
      substrate, the spatial changes in the direction from the front to the rear of the
      cell reflect temporal changes in the actin network after its assembly at the
      leading edge. We have utilized atomic force microscopy to determine the rigidity
      of fish keratocyte lamellipodia as a function of time/distance from the leading
      edge. Although vertical thickness remained nearly constant throughout the
      lamellipodia, the rigidity exhibited a gradual but significant decrease from the
      front to the rear of the lamellipodia. The rigidity profile resembled closely the
      actin density profile, suggesting that the dynamics of rigidity are due to actin
      depolymerization. The decrease of rigidity may play a role in facilitating the
      contraction of the actin-myosin network at the lamellipodium/cell body transition
      zone.

PMID- 15849254
TI  - The pore, not cytoplasmic domains, underlies inactivation in a prokaryotic sodium
      channel.
AB  - Kinetics and voltage dependence of inactivation of a prokaryotic voltage-gated
      sodium channel (NaChBac) were investigated in an effort to understand its
      molecular mechanism. NaChBac inactivation kinetics show strong, bell-shaped
      voltage dependence with characteristic time constants ranging from approximately
      50 ms at depolarized voltages to a maximum of approximately 100 s at the
      inactivation midpoint. Activation and inactivation parameters for four different
      covalently linked tandem dimer or tandem tetramer constructs were
      indistinguishable from those of the wild-type channel. Point mutations in the
      outer part of the pore revealed an important influence of the S195 residue on the
      process of inactivation. For two mutants (S195D and S195E), the maximal and
      minimal rates of inactivation observed were increased by approximately 2.5-fold,
      and the midpoint of the steady-state inactivation curve was shifted approximately
      20 mV in the hyperpolarizing direction, compared to the wild-type channel. Our
      data suggest that pore vestibule structure is an important determinant of NaChBac
      inactivation, whereas the inactivation mechanism is independent of the number of
      free cytoplasmic N- and C-termini in the functional channel. In these respects,
      NaChBac inactivation resembles C-type or slow inactivation modes observed in
      other voltage-gated K and Na channels.

PMID- 15849255
TI  - Fast, triangular voltage clamp for recording and kinetic analysis of an ion
      transporter expressed in Xenopus oocytes.
AB  - We present a procedure for determination of 11 system parameters of an ion
      transporter expressed in Xenopus oocytes. The experiments consist of fast
      triangular voltage-clamp experiments in the presence and absence of external
      substrate. A four-state enzymatic cycle operating between an external and an
      internal section of electrodiffusion is used for analysis. The explicit example
      treats experiments with the fungal 2H+-NO3- symporter EnNRT, a member of the
      major superfamily transporters. The results comprise a density of approximately
      150 fmol functional transporter molecules per oocyte, a gross charge number z(E)
      approximately -0.3 of the empty binding site of the enzyme, individual rate
      constants for reorientation of the empty and occupied binding site in the range
      of 5-500 s(-1), electrical access sections between bulk solutions and reaction
      cycle of approximately 3% inside and 15% outside, an increase of internal NO3- at
      the plasma membrane from approximately 0.5 to approximately 2 mM during exposure
      to external NO3-, and K(D) approximately 0.3 microM3 inside and K(D)
      approximately 3 microM3 outside in binding the triplicate substrate (2H+ +NO3-).
      The results compare well with the known structure of the lactose permease,
      another major superfamily transporter.

PMID- 15849256
TI  - Muscle contraction: actin filaments enter the fray.

PMID- 15849257
TI  - Structural elements in IGP synthase exclude water to optimize ammonia transfer.
AB  - In the complex pathway of histidine biosynthesis, a key branch point linking
      amino acid and purine biosynthesis is catalyzed by the bifunctional enzyme
      imidazole glycerol phosphate (IGP) synthase. The first domain of IGP synthase, a
      triad glutamine amidotransferase, hydrolyzes glutamine to form glutamate and
      ammonia. Its activity is tightly regulated by the binding of the substrate PRFAR
      to its partner synthase domain. Recent crystal structures and molecular dynamics
      simulations strongly suggest that the synthase domain, a (beta/alpha)(8) barrel
      protein, mediates the insertion of ammonia and ring formation in IGP by
      channeling ammonia from one remote active site to the other. Here, we combine
      both mutagenesis experiments and computational investigations to gain insight
      into the transfer of ammonia and the mechanism of conduction. We discover an
      alternate route for the entrance of ammonia into the (beta/alpha)(8) barrel and
      argue that water acts as both agonist and antagonist to the enzymatic function.
      Our results indicate that the architecture of the two subdomains, most notably
      the strict conservation of key residues at the interface and within the
      (beta/alpha)(8) barrel, has been optimized to allow the efficient passage of
      ammonia, and not water, between the two remote active sites.

PMID- 15849258
TI  - Spontaneous synchronization of coupled circadian oscillators.
AB  - In mammals, the circadian pacemaker, which controls daily rhythms, is located in
      the suprachiasmatic nucleus (SCN). Circadian oscillations are generated in
      individual SCN neurons by a molecular regulatory network. Cells oscillate with
      periods ranging from 20 to 28 h, but at the tissue level, SCN neurons display
      significant synchrony, suggesting a robust intercellular coupling in which
      neurotransmitters are assumed to play a crucial role. We present a dynamical
      model for the coupling of a population of circadian oscillators in the SCN. The
      cellular oscillator, a three-variable model, describes the core negative feedback
      loop of the circadian clock. The coupling mechanism is incorporated through the
      global level of neurotransmitter concentration. Global coupling is efficient to
      synchronize a population of 10,000 cells. Synchronized cells can be entrained by
      a 24-h light-dark cycle. Simulations of the interaction between two populations
      representing two regions of the SCN show that the driven population can be phase
      leading. Experimentally testable predictions are: 1), phases of individual cells
      are governed by their intrinsic periods; and 2), efficient synchronization is
      achieved when the average neurotransmitter concentration would dampen individual
      oscillators. However, due to the global neurotransmitter oscillation, cells are
      effectively synchronized.

PMID- 15849260
TI  - New aac(6')-I genes in Enterococcus hirae and Enterococcus durans: effect on
      {beta}-lactam/aminoglycoside synergy.

PMID- 15849259
TI  - Electrochemical and PM-IRRAS studies of the effect of cholesterol on the
      structure of a DMPC bilayer supported at an Au (111) electrode surface, part 1:
      properties of the acyl chains.
AB  - Charge density measurements and polarization modulation infrared reflection
      absorption spectroscopy were employed to investigate the spreading of small
      unilamellar vesicles of a dimyristoylphosphatidylcholine (DMPC)/cholesterol (7:3
      molar ratio) mixture onto an Au (111) electrode surface. The electrochemical
      experiments demonstrated that vesicles fuse and spread onto the Au (111)
      electrode surface, forming a bilayer, at rational potentials -0.4 V < (E - Epzc)
      < 0.4 V or field strength <6 x 10(7) V m(-1). Polarization modulation infrared
      reflection absorption spectroscopy experiments provided information concerning
      the conformation and orientation of the acyl chains of DMPC molecules. Deuterated
      DMPC was used to subtract the contribution of C-H stretching bands of cholesterol
      and of the polar head region of DMPC from spectra in the C-H stretching region.
      The absorption spectra of the C-H stretch bands in the acyl chains were
      determined in this way. The properties of the DMPC/cholesterol bilayer have been
      compared with the properties of a pure DMPC bilayer. The presence of 30%
      cholesterol gives a thicker and more fluid bilayer characterized by a lower
      capacity and lower tilt angle of the acyl chains.

PMID- 15849261
TI  - Switch strategies in patients on effective HAART.
AB  - To provide the best possible long-term outcomes for patients, a number of
      strategies have been proposed based on the possibility to switch from a
      successful protease inhibitor (PI)-based highly active antiretroviral therapy
      (HAART) to another antiretroviral regimen. The available evidence from clinical
      trials in virologically controlled patients demonstrates that switching the PI
      based HAART to a simplified regimen is safe. However, abacavir-based simplified
      therapies should be limited to patients with a known drug history who have not
      undergone prior mono or dual nucleoside/nucleotide reverse transcriptase
      inhibitor (NRTI) therapy. Triple NRTI regimens that do not include a thymidine
      analogue have not been adequately tested so far and are not recommended. The
      switch strategy may enhance long-term adherence and induce a moderate reduction
      in cholesterol or amelioration of the total/high-density lipoprotein (HDL)
      cholesterol ratio that might be particularly relevant for patients presenting
      other risks for coronary heart disease. Simplified regimens are not associated
      with a clinically relevant improvement in the redistribution of body fat. Thus,
      if such a therapeutic strategy is considered, it should be preferably implemented
      to prevent or delay lipodystrophy. As the therapeutic scenario is significantly
      changing, in the future, convenience and metabolic alterations will be less of an
      issue in the decision to use a PI-switch strategy. Future switch strategies may
      involve NRTIs. Among NRTIs, thymidine analogues and particularly stavudine appear
      to be most associated with lipoatrophy. NRTI switches may also be beneficial in
      reducing the risk of lactate level elevation, mitochondrial toxicity,
      insufficient immunological response to HAART and of selecting class-inducing
      resistance mutations.

PMID- 15849262
TI  - In vitro susceptibilities of aerobic and facultative Gram-negative bacilli
      isolated from patients with intra-abdominal infections worldwide: the 2003 Study
      for Monitoring Antimicrobial Resistance Trends (SMART).
AB  - OBJECTIVES: The SMART (Study for Monitoring Antimicrobial Resistance Trends)
      surveillance programme was begun in 2002 to monitor antimicrobial resistance
      trends among aerobic and facultative Gram-negative bacilli (GNB) isolated from
      intra-abdominal infections worldwide. METHODS: In 2003, 74 medical centres from
      23 countries collected isolates for testing. Antimicrobial susceptibility testing
      was performed using broth microdilution according to the NCCLS guidelines for MIC
      testing. RESULTS: A total of 5658 aerobic and facultative GNB were isolated from
      intra-abdominal infections. Enterobacteriaceae composed 84% of the total
      isolates. Among the agents tested, the carbapenems were the most consistently
      active against the Enterobacteriaceae. E. coli was the most common isolate (46%),
      and the susceptibility rate to the quinolone (70-90% susceptible), cephalosporin
      (80-97% susceptible), aminoglycoside (77-100% susceptible) and carbapenem (99
      100% susceptible) agents tested varied among geographic regions, with isolates
      from the Asia/Pacific region generally being the most resistant. Extended
      spectrum beta-lactamases (ESBLs) were detected phenotypically in 9% of E. coli,
      14% of Klebsiella spp., and 14% of Enterobacter spp. worldwide. ESBL producers
      generally had a more antibiotic-resistant profile than non-ESBL producers.
      CONCLUSIONS: Antimicrobial resistance among GNB isolated from intra-abdominal
      infections is a problem worldwide, especially in the Asia/Pacific region. The
      carbapenems ertapenem, meropenem and imipenem are highly active in vitro against
      Enterobacteriaceae isolated from intra-abdominal sites, including organisms that
      produce ESBLs.

PMID- 15849263
TI  - Lamivudine prophylaxis in HBV carriers with haemato-oncological malignancies who
      receive chemotherapy.
AB  - Reactivation of hepatitis B virus (HBV) is a well-recognized complication of
      chemo/immunosuppressive therapy in individuals who are HBV surface antigen
      positive inactive carriers and in individuals with chronic HBV infection.
      Although it is well established that chemo/immunosuppressive therapy enhances HBV
      replication with a resultant increase in the viral load and disease activation,
      the role of prophylactic lamivudine therapy to prevent chemo/immunosuppressive
      therapy-induced HBV activation in HBV-positive individuals who are to receive
      chemo/immunosuppressive therapy remains controversial. The aims of the present
      article are: (i) to determine the effect of lamivudine prophylaxis in HBV
      carriers with haemato-oncological malignancies who require chemotherapy; (ii) to
      define the duration and safety of lamivudine in such individuals; and (iii) to
      identify the effect of lamivudine prophylaxis on the outcome of chemotherapy
      administered for the primary disease. The data currently available suggest that
      lamivudine prophylaxis prevents chemotherapy-induced HBV reactivation in HBV
      carriers with haemato-oncological malignancies who receive chemotherapy.
      Lamivudine is safe and tolerable in such individuals. The duration of lamivudine
      prophylaxis is not yet known; however, it would appear prudent to begin
      lamivudine at the time of the initiation of the chemotherapy and to continue it
      throughout the period of chemotherapy administration and for at least 1 and
      possibly 2 years following the discontinuation of the chemotherapy. Finally, the
      prophylactic use of lamivudine in inactive HBV carriers with haemato-oncological
      malignancy prevents interruptions in their treatment for primary disease as a
      result of HBV reactivation.

PMID- 15849264
TI  - Functional analysis of the pseudoknot structure in human telomerase RNA.
AB  - Telomerase is essential for maintaining telomere length and chromosome stability
      in stem cells, germline cells, and cancer cells. The telomerase ribonucleoprotein
      complex consists of two essential components, a catalytic protein component and
      an RNA molecule that provides the template for telomeric repeat synthesis. A
      pseudoknot structure in the human telomerase RNA is conserved in all vertebrates
      and is essential for telomerase activity. It has been proposed that this highly
      conserved structure functions as a dynamic structure with conformational
      interchange between the pseudoknot and a hairpin with intraloop base pairings. To
      examine the structural and functional requirements of the pseudoknot structure,
      we made mutations in the proposed base-paired regions in the pseudoknot. Although
      mutations that disrupted the pseudoknot P3 helix abolished activity as predicted,
      mutations that disrupted the intraloop hairpin base pairings did not reduce
      telomerase activity, indicating that the intraloop hairpin is not required for
      telomerase function. This functional study thus provides evidence against the
      previous proposed molecular-switch model of telomerase pseudoknot function and
      supports a static pseudoknot structure. The mutational analysis further suggests
      that telomerase RNA can function independent of the proposed intermolecular
      pairings between pseudoknot regions on two RNA molecules.

PMID- 15849265
TI  - Capturing protein interactions in the secretory pathway of living cells.
AB  - The secretory pathway is composed of membrane compartments specialized in protein
      folding, modification, transport, and sorting. Numerous transient protein-protein
      interactions guide the transport-competent proteins through the secretory
      pathway. Here we have adapted the yellow fluorescent protein (YFP)-based protein
      fragment complementation assay (PCA) to detect protein-protein interactions in
      the secretory pathway of living cells. Fragments of YFP were fused to the
      homooligomeric cargo-receptor lectin endoplasmic reticulum Golgi intermediate
      compartment (ERGIC)-53, to the ERGIC-53-interacting multi-coagulation factor
      deficiency protein MCFD2, and to ERGIC-53's cargo glycoprotein cathepsin Z. YFP
      PCA analysis revealed the oligomerization of ERGIC-53 and its interaction with
      MCFD2, as well as its lectin-mediated interaction with cathepsin Z. Mutation of
      the lectin domain of ERGIC-53 selectively decreased YFP complementation with
      cathepsin Z. Using YFP PCA, we discovered a carbohydrate-mediated interaction
      between ERGIC-53 and cathepsin C. We conclude that YFP PCA can detect weak and
      transient protein interactions in the secretory pathway and hence is a powerful
      approach to study luminal processes involved in protein secretion. The study
      extends the application of PCA to carbohydrate-mediated protein-protein
      interactions of low affinity.

PMID- 15849266
TI  - E1A and a nuclear receptor corepressor splice variant (N-CoRI) are thyroid
      hormone receptor coactivators that bind in the corepressor mode.
AB  - Unliganded thyroid hormone (TH) receptors (TRs) and other nuclear receptors (NRs)
      repress transcription of hormone-activated genes by recruiting corepressors
      (CoRs), such as NR CoR (N-CoR) and SMRT. Unliganded TRs also activate
      transcription of TH-repressed genes. Some evidence suggests that these effects
      also involve TR/CoR contacts; however, the precise reasons that CoRs activate
      transcription in these contexts are obscure. Unraveling these mechanisms is
      complicated by the fact that it is difficult to decipher direct vs. indirect
      effects of TR-coregulator contacts in mammalian cells. In this study, we used
      yeast, Saccharomyces cerevisiae, which lack endogenous NRs and NR coregulators,
      to determine how unliganded TRs can activate transcription. We previously showed
      that adenovirus 5 early-region 1A coactivates unliganded TRs in yeast, and that
      these effects are blocked by TH. We show here that human adenovirus type 5 early
      region 1A (E1A) contains a short peptide (LDQLIEEVL amino acids 20-28) that
      resembles CoR-NR interaction motifs (CoRNR boxes), and that this motif is
      required for TR binding and coactivation. Although full-length N-CoR does not
      coactivate TR in yeast, a naturally occurring N-CoR variant (N-CoR(I)) and an
      artificial N-CoR truncation (N-CoR(C)) that retain CoRNR boxes but lack N
      terminal repressor domains behave as potent and direct TH-repressed coactivators
      for unliganded TRs. We conclude that E1A and N-CoR(I) are naturally occurring TR
      coactivators that bind in the typical CoR mode and suggest that similar factors
      could mediate transcriptional activation by unliganded TRs in mammals.

PMID- 15849267
TI  - Invasion success of vertebrates in Europe and North America.
AB  - Species become invasive if they (i) are introduced to a new range, (ii) establish
      themselves, and (iii) spread. To address the global problems caused by invasive
      species, several studies investigated steps ii and iii of this invasion process.
      However, only one previous study looked at step i and examined the proportion of
      species that have been introduced beyond their native range. We extend this
      research by investigating all three steps for all freshwater fish, mammals, and
      birds native to Europe or North America. A higher proportion of European species
      entered North America than vice versa. However, the introduction rate from Europe
      to North America peaked in the late 19th century, whereas it is still rising in
      the other direction. There is no clear difference in invasion success between the
      two directions, so neither the imperialism dogma (that Eurasian species are
      exceptionally successful invaders) is supported, nor is the contradictory
      hypothesis that North America offers more biotic resistance to invaders than
      Europe because of its less disturbed and richer biota. Our results do not support
      the tens rule either: that approximately 10% of all introduced species establish
      themselves and that approximately 10% of established species spread. We find a
      success of approximately 50% at each step. In comparison, only approximately 5%
      of native vertebrates were introduced in either direction. These figures show
      that, once a vertebrate is introduced, it has a high potential to become
      invasive. Thus, it is crucial to minimize the number of species introductions to
      effectively control invasive vertebrates.

PMID- 15849268
TI  - A point mutation in the groove of HLA-DO allows egress from the endoplasmic
      reticulum independent of HLA-DM.
AB  - B lymphocytes express the nonclassical class II molecule HLA-DO, which modulates
      the peptide loading activity of HLA-DM in the endocytic pathway. Binding to HLA
      DM is required for HLA-DO to egress from the endoplasmic reticulum (ER). To gain
      insights into the mode of action of DO and on the role of DM in ER release, we
      sought to identify DM-binding residues on DO. Our results show that DOalpha
      encompasses the binding site for HLA-DM. More specifically, mutation of residue
      DOalpha41 on an exposed lateral loop of the alpha1 domain affects the binding to
      DM, ER egress, and activity of DO. Using a series of chimeric DR/DO molecules, we
      confirmed the role of the alpha chain and established that a second DM-binding
      region is located C-terminal to the DOalpha80 residue, most probably in the
      alpha2 domain. Interestingly, after mutation of a buried proline (alpha11) on the
      floor of the putative peptide-binding groove, HLA-DO remained functional but
      became independent of HLA-DM for ER egress and intracellular trafficking.
      Collectively, these results suggest that the binding of HLA-DM to DOalpha allows
      the complex to egress from the ER by stabilizing intramolecular contacts between
      the N-terminal antiparallel beta-strands of the DOalphabeta heterodimer.

PMID- 15849269
TI  - Quantum corrections in vibrational and electronic condensed phase spectroscopy:
      line shapes and echoes.
AB  - Various linear and nonlinear vibrational and electronic spectroscopy experiments
      in liquids are usually analyzed within the second-cumulant approximation, and
      therefore the fundamental quantity of interest is the equilibrium time
      correlation function of the fluctuating transition frequency. In the usual
      approach the "bath" variables responsible for the fluctuating frequency are
      treated classically, leading to a classical time-correlation function.
      Alternatively, sometimes a quantum correction appropriate for relatively high
      temperatures is included, which adds an imaginary part to the classical time
      correlation function. This approach, although appealing, does not satisfy
      detailed balance. One can consider a similar correction, but where detailed
      balance is satisfied, by using the harmonic quantum correction factor. In this
      article, we compare these approaches for a model system and two realistic
      examples. Our conclusion is that for linear spectroscopy the classical result is
      usually adequate, whereas for nonlinear spectroscopy it can be more important to
      include quantum corrections.

PMID- 15849271
TI  - Quantitative proteomic analysis using isobaric protein tags enables rapid
      comparison of changes in transcript and protein levels in transformed cells.
AB  - Isobaric tags for relative and absolute quantitation, an approach to concurrent,
      relative quantification of proteins present in four cell preparations, have
      recently been described. To validate this approach using complex mammalian cell
      samples that show subtle differences in protein levels, a model stem cell-like
      cell line (FDCP-mix) in the presence or absence of the leukemogenic oncogene
      TEL/PDGFRbeta has been studied. Cell lysates were proteolytically digested, and
      peptides within each sample were labeled with one of four isobaric, isotope-coded
      tags via their N-terminal and/or lysine side chains. The four labeled samples are
      mixed and peptides separated by two-dimensional liquid chromatography online to a
      mass spectrometer (LC-MS). Upon peptide fragmentation, each tag releases a
      distinct mass reporter ion; the ratio of the four reporters therefore gives
      relative abundances of the given peptide. Relative quantification of proteins is
      derived using summed data from a number of peptides. TEL/PDGFRbeta leukemic
      oncogene-mediated changes in protein levels were compared with those seen in
      microarray analysis of control and transfected FDCP-mix cells. Changes at the
      protein level in most cases reflected those seen at the transcriptome level.
      Nonetheless, novel differences in protein expression were found that indicate
      potential mechanisms for effects of this oncogene.

PMID- 15849270
TI  - roundabout4 is essential for angiogenesis in vivo.
AB  - Stereotypical patterns of vascular and neuronal networks suggest that specific
      genetic programs tightly control path determination and, consequently,
      angiogenesis and axon-guidance mechanisms. Our study focuses on one member of the
      roundabout family of receptors, which traditionally mediate repulsion from the
      midline. Here, we characterize a fourth member of this family, roundabout4
      (robo4), which is the predominant roundabout (robo) that is expressed in
      embryonic zebrafish vasculature. Gene knockdown and overexpression approaches
      show that robo4 is essential for coordinated symmetric and directed sprouting of
      intersomitic vessels and provide mechanistic insights into this process. Also,
      human robo4 gene functionally compensates for loss of robo4 gene function,
      suggesting evolutionary conservation. This article reports an endothelial
      specific function for a robo gene in vertebrates in vivo.

PMID- 15849272
TI  - Metabolic labeling of proteins for proteomics.
AB  - Realization of the advantages of stable isotope labeling for proteomics has
      emerged gradually. However, many stable isotope label approaches rely on labeling
      in vitro using complex and sometimes expensive reagents. This review discusses
      strategies for labeling protein in vivo through metabolic incorporation of label
      into protein. This approach has many advantages, is particularly suited to single
      cells grown in culture (prokaryotic or eukaryotic), but is nonetheless subject to
      a number of complicating factors that must be controlled so that meaningful
      experiments can be conducted. Confounding issues include the metabolic lability
      of the amino acid precursor, incomplete labeling, and the role of protein
      turnover in labeling kinetics. All of these are controllable, provided that
      appropriate precautions are adopted.

PMID- 15849273
TI  - Antiquity of microRNAs and their targets in land plants.
AB  - MicroRNAs (miRNAs) affect the morphology of flowering plants by the
      posttranscriptional regulation of genes involved in critical developmental
      events. Understanding the spatial and temporal dynamics of miRNA activity during
      development is therefore central for understanding miRNA functions. We describe a
      microarray suitable for detection of plant miRNAs. Profiling of Arabidopsis
      thaliana miRNAs during normal development extends previous expression analyses,
      highlighting differential expression of miRNA families within specific organs and
      tissue types. Comparison of our miRNA expression data with existing mRNA
      microarray data provided a global intersection of plant miRNA and mRNA expression
      profiles and revealed that tissues in which a given miRNA is highly expressed are
      unlikely to also show high expression of the corresponding targets. Expression
      profiling was also used in a phylogenetic survey to test the depth of plant miRNA
      conservation. Of the 23 families of miRNAs tested, expression of 11 was detected
      in a gymnosperm and eight in a fern, directly demonstrating that many plant
      miRNAs have remained essentially unchanged since before the emergence of
      flowering plants. We also describe an empirical strategy for detecting miRNA
      target genes from unsequenced transcriptomes and show that targets in
      nonflowering plants as deeply branching as ferns and mosses are homologous to the
      targets in Arabidopsis. Therefore, several individual miRNA regulatory circuits
      have ancient origins and have remained intact throughout the evolution and
      diversification of plants.

PMID- 15849274
TI  - COBRA, an Arabidopsis extracellular glycosyl-phosphatidyl inositol-anchored
      protein, specifically controls highly anisotropic expansion through its
      involvement in cellulose microfibril orientation.
AB  - The orientation of cell expansion is a process at the heart of plant
      morphogenesis. Cellulose microfibrils are the primary anisotropic material in the
      cell wall and thus are likely to be the main determinant of the orientation of
      cell expansion. COBRA (COB) has been identified previously as a potential
      regulator of cellulose biogenesis. In this study, characterization of a null
      allele, cob-4, establishes the key role of COB in controlling anisotropic
      expansion in most developing organs. Quantitative polarized-light and field
      emission scanning electron microscopy reveal that loss of anisotropic expansion
      in cob mutants is accompanied by disorganization of the orientation of cellulose
      microfibrils and subsequent reduction of crystalline cellulose. Analyses of the
      conditional cob-1 allele suggested that COB is primarily implicated in
      microfibril deposition during rapid elongation. Immunodetection analysis in
      elongating root cells revealed that, in agreement with its substitution by a
      glycosylphosphatidylinositol anchor, COB was polarly targeted to both the plasma
      membrane and the longitudinal cell walls and was distributed in a banding pattern
      perpendicular to the longitudinal axis via a microtubule-dependent mechanism. Our
      observations suggest that COB, through its involvement in cellulose microfibril
      orientation, is an essential factor in highly anisotropic expansion during plant
      morphogenesis.

PMID- 15849275
TI  - Mechanisms of derived unitegmy among Impatiens species.
AB  - Morphological transitions associated with ovule diversification provide unique
      opportunities for studies of developmental evolution. Here, we investigate the
      underlying mechanisms of one such transition, reduction in integument number,
      which has occurred several times among diverse angiosperms. In particular,
      reduction in integument number occurred early in the history of the asterids, a
      large clade comprising approximately one-third of all flowering plants. Unlike
      the vast majority of other eudicots, nearly all asterids have a single
      integument, with the only exceptions in the Ericales, a sister group to the other
      asterids. Impatiens, a genus of the Ericales, includes species with one
      integument, two integuments, or an apparently intermediate bifid integument. A
      comparison of the development of representative Impatiens species and analysis of
      the expression patterns of putative orthologs of the Arabidopsis thaliana ovule
      development gene INNER NO OUTER (INO) has enabled us to propose a mechanism
      responsible for morphological transitions between integument types in this group.
      We attribute transitions between each of the three integument morphologies to
      congenital fusion via a combination of variation in the location of subdermal
      growth beneath primordia and the merging of primordia. Evidence of multiple
      transitions in integument morphology among Impatiens species suggests that
      control of underlying developmental programs is relatively plastic and that
      changes in a small number of genes may have been responsible for the transitions.
      Our expression data also indicate that the role of INO in the outgrowth and
      abaxial-adaxial polarity of the outer integument has been conserved between two
      divergent angiosperms, the rosid Arabidopsis and the asterid Impatiens.

PMID- 15849276
TI  - Development and initial validation of the Brunel lifestyle physical activity
      questionnaire.
AB  - OBJECTIVES: To develop a valid and reliable internet based lifestyle physical
      activity questionnaire suitable for use among the United Kingdom population.
      METHODS: After a detailed content analysis and item generation using a panel of
      experts, an internet based measure of lifestyle physical activity behaviour was
      developed. Data were collected from 1369 subjects in total. Confirmatory factor
      analysis was used to examine the two subscales of the Brunel lifestyle physical
      activity questionnaire among independent samples and by use of multisample
      analyses. RESULTS: The confirmatory factor analysis showed the psychometric
      integrity of two subscales: planned physical activity and unplanned physical
      activity. CONCLUSION: The questionnaire is a valid and reliable instrument
      designed to provide an online behavioural assessment to be used in conjunction
      with a 12 week personalised fitness programme delivered through the internet.

PMID- 15849277
TI  - Acute effects of a single open sea air dive and post-dive posture on cardiac
      output and pulmonary gas exchange in recreational divers.
AB  - OBJECTIVE: To evaluate the cardiopulmonary effects of open sea scuba air diving
      to 39 m (30 minutes bottom time) with standard decompression. To account for
      possible gravity dependent effects of venous gas bubbles, the variables were
      measured in different post-dive body postures and compared with the baseline
      values before the dive in the same posture. METHODS: Eight male divers conducted
      two similar dives on successive days. Their posture before and after the dive was
      either sitting or supine, in random order. The divers were evaluated before and
      30, 60, and 90 minutes after the dive. Venous bubbles were detected by precordial
      Doppler after the dive in four divers in the supine posture and two divers in the
      sitting posture. RESULTS: Arterialised oxygen tension had decreased at all times
      after the dive (-11.3 mm Hg, p = 0.00006), due to decreased alveolar oxygen
      tension, irrespective of posture. Apart from an increase in the sitting posture
      30 minutes after the dive, pulmonary capacity for carbon monoxide diffusion and
      cardiac index decreased, mostly 60 minutes after the dive (-9%, p = 0.0003 and 
      20%, p = 0.0002 respectively). The decrease in cardiac index was greater in the
      supine posture (p = 0.0004), and the physiological dead space/tidal volume ratio
      increased more in the sitting position (p = 0.006). CONCLUSIONS: Field dives are
      associated with moderate impairments in cardiac output and gas exchange. Some of
      these impairments appear to depend on the posture of the diver after the dive.

PMID- 15849278
TI  - High strain mechanical loading rapidly induces tendon apoptosis: an ex vivo rat
      tibialis anterior model.
AB  - BACKGROUND: The role of apoptosis, or programmed cell death, has only recently
      been explored in tendon. OBJECTIVE: To investigate the development of apoptosis
      after high strain loading of rat tendon. METHODS: The right tibialis anterior
      tendons of three rats were prepared for mechanical loading, and left tendons were
      prepared identically as non-loaded controls. Tendon was loaded with 20% strain
      for six hours using a 1 Hz longitudinal sine wave signal. The following were used
      to assess apoptosis: (a) a monoclonal mouse antibody (F7-26) to label single
      stranded DNA breaks; (b) a rabbit polyclonal antibody that specifically
      recognises the cleaved form of caspase-3. RESULTS: Light microscopy confirmed
      that the high strain protocol induced a stretch overload injury. Control tendons
      showed little or no staining with the F7-26 antibody, but the loaded tendons
      displayed numerous apoptotic cells. The percentage of apoptotic cells (20%) in
      the loaded tendon was significantly greater than in the control tendon (1%) (p =
      0.000). The labelled cells colocalised with abnormal nuclear morphology,
      including nuclear fragmentation. The staining against cleaved caspase-3 was
      positive in loaded tendons only, and localised both to nucleus and cytoplasm.
      CONCLUSION: This experiment extends knowledge of human tendon apoptosis by
      showing that apoptosis can occur in response to short term, high strain
      mechanical loading. This is the first report of mechanical loading of intact
      tendon causing excessive apoptosis.

PMID- 15849279
TI  - The kick with the kite: an analysis of kite surfing related off shore rescue
      missions in Cape Town, South Africa.
AB  - BACKGROUND: This study analyses kite surfing related off shore rescue missions in
      Cape Town, South Africa with the aim of providing more information on the
      frequency, pattern, and severity of kite surfing related injuries. METHODS: The
      observation period for this study started on October 1, 2003 and ended on May 1,
      2004 and included 30 air rescue missions. Data and information were collected
      prospectively. RESULTS: The Air Mercy Service in Cape Town Province responded to
      30 requests for help. Twenty five accidents were attributed to inability to
      detach the kite from the harness. Injuries occurred in five incidents and
      included fractures of the upper arm, ribs and ankle, and lacerations and
      contusions to the head and neck. Two patients suffered from hypothermia and one
      experienced severe exhaustion. All surfers were rescued successfully and there
      were no fatal accidents. DISCUSSION: The risk potential of this new sport is
      unclear. Dangerous situations can occur despite proper training and safety
      precautions due to unpredictable conditions and difficulties with equipment.
      Safety should be stressed. Surfers should sailing with a fellow kiter and should
      wear a life vest. More efforts must be taken to make this booming new water sport
      safer.

PMID- 15849280
TI  - Hepatocellular adenomas associated with anabolic androgenic steroid abuse in
      bodybuilders: a report of two cases and a review of the literature.
AB  - Anabolic androgenic steroids (AAS) are used illicitly at high doses by
      bodybuilders. The misuse of these drugs is associated with serious adverse
      effects to the liver, including cellular adenomas and adenocarcinomas. We report
      two very different cases of adult male bodybuilders who developed hepatocellular
      adenomas following AAS abuse. The first patient was asymptomatic but had two
      large liver lesions which were detected by ultrasound studies after routine
      medical examination. The second patient was admitted to our hospital with acute
      renal failure and ultrasound (US) studies showed mild hepatomegaly with several
      very close hyperecogenic nodules in liver, concordant with adenomas at first
      diagnosis. In both cases the patients have evolved favourably and the tumours
      have shown a tendency to regress after the withdrawal of AAS. The cases presented
      here are rare but may well be suggestive of the natural course of AAS induced
      hepatocellular adenomas. In conclusion, sportsmen taking AAS should be considered
      as a group at risk of developing hepatic sex hormone related tumours.
      Consequently, they should be carefully and periodically monitored with US
      studies. In any case, despite the size of the tumours detected in these two
      cases, the possibility of spontaneous tumour regression must also be taken in
      account.

PMID- 15849281
TI  - Posterior sternoclavicular dislocation in a rugby player as a cause of silent
      vascular compromise: a case report.
AB  - BACKGROUND: Approximately 120 cases of posterior sternoclavicular joint (SCJ)
      dislocation have been documented in the medical literature since it was first
      described in 1824 by Sir Astley Cooper, a statistic which underlies its relative
      rarity. It is associated with high energy trauma, and although it may present
      innocently enough, it is a potentially life threatening injury. CASE AND RESULTS:
      We describe a case in which there was no clinical evidence of complication,
      although CT imaging revealed complete obstruction of the brachiocephalic vein and
      impingement of the aorta. This required open reduction and a novel fixation
      technique was employed. The reduction was stable at 8 month follow up appointment
      as evidenced by CT scan. CONCLUSIONS: We acknowledge that this type of
      complication is well recognised but emphasise that it should not be managed
      complacently. A high index of suspicion is required to determine the presence of
      serious complications in this type of injury, which may manifest insidiously.

PMID- 15849282
TI  - A cause for concern?

PMID- 15849283
TI  - Sport and exercise medicine in the United Kingdom comes of age.

PMID- 15849284
TI  - Can oestrogen influence skeletal muscle damage, inflammation, and repair?

PMID- 15849286
TI  - Craniomaxillofacial injury in sport: a review of prevention research.
AB  - Current decision making in prevention of sport related craniomaxillofacial injury
      is based on available data derived from surveillance and attitude based studies.
      The literature on this type of injury prevention lacks the high quality
      scientific design and evidence on which mandatory interventions can be based.
      Currently available prevention methodology can provide a better understanding of
      injury mechanisms and produce valid interventions.

PMID- 15849287
TI  - Physiological profile in relation to playing position of elite college Gaelic
      footballers.
AB  - OBJECTIVE: To examine the physiological profile, and its relation to playing
      position, of elite college Gaelic footballers. METHOD: The subjects were 28 elite
      Gaelic footballers (12 backs, 12 forwards, and four midfielders; mean (SD) age 21
      (1.67) years), who won a major intervarsity tournament (Sigerson Cup) three times
      in succession. RESULTS: There was general similarity among the members of the
      team, probably the result of a typical, common training programme. The team means
      for stature (1.81 (0.05) m), body mass index (81.6 (6.5)) and percentage body fat
      (14.5 (3.1)%), power output by Wingate test (absolute power 912 (152) W or 10.72
      (1.6) W/kg) and sit and reach test (22.3 (5.5) cm) displayed no significant
      differences when analysed according to playing position. However, midfielders did
      have significantly larger body mass than backs (p<0.05) and greater maximal
      oxygen consumption (p<0.01) and greater vertical jumping ability than backs and
      forwards (vertical jump power output, p<0.01; vertical jump, p<0.01). Midfielders
      also had greater absolute handgrip strength (p<0.01). CONCLUSION: The differences
      exhibited by midfielders despite identical training suggests that they stem from
      physiological adaptation to competition rather than training.

PMID- 15849289
TI  - Cadence selection affects metabolic responses during cycling and subsequent
      running time to fatigue.
AB  - OBJECTIVES: To investigate the effect of cadence selection during the final
      minutes of cycling on metabolic responses, stride pattern, and subsequent running
      time to fatigue. METHODS: Eight triathletes performed, in a laboratory setting,
      two incremental tests (running and cycling) to determine peak oxygen uptake
      (VO2PEAK) and the lactate threshold (LT), and three cycle-run combinations.
      During the cycle-run sessions, subjects completed a 30 minute cycling bout (90%
      of LT) at (a) the freely chosen cadence (FCC, 94 (5) rpm), (b) the FCC during the
      first 20 minutes and FCC-20% during the last 10 minutes (FCC-20%, 74 (3) rpm), or
      (c) the FCC during the first 20 minutes and FCC+20% during the last 10 minutes
      (FCC+20%, 109 (5) rpm). After each cycling bout, running time to fatigue (Tmax)
      was determined at 85% of maximal velocity. RESULTS: A significant increase in
      Tmax was found after FCC-20% (894 (199) seconds) compared with FCC and FCC+20%
      (651 (212) and 624 (214) seconds respectively). VO2, ventilation, heart rate, and
      blood lactate concentrations were significantly reduced after 30 minutes of
      cycling at FCC-20% compared with FCC+20%. A significant increase in VO2 was
      reported between the 3rd and 10th minute of all Tmax sessions, without any
      significant differences between sessions. Stride pattern and metabolic variables
      were not significantly different between Tmax sessions. CONCLUSIONS: The increase
      in Tmax after FCC-20% may be associated with the lower metabolic load during the
      final minutes of cycling compared with the other sessions. However, the lack of
      significant differences in metabolic responses and stride pattern between the run
      sessions suggests that other mechanisms, such as changes in muscular activity,
      probably contribute to the effects of cadence variation on Tmax

PMID- 15849290
TI  - Physiological adaptations to soccer specific endurance training in professional
      youth soccer players.
AB  - BACKGROUND: Improved oxygen uptake improves soccer performance as regards
      distance covered, involvements with the ball, and number of sprints. Large
      improvements in oxygen uptake have been shown using interval running. A similar
      physiological load arising from interval running could be obtained using the
      soccer ball in training. OBJECTIVES: The main aim was to study physiological
      adaptations to a 10 week high intensity aerobic interval training program
      performed by professional youth soccer players, using a soccer specific ball
      dribbling track. METHODS: Eleven youth soccer players with a mean (SD) age of
      16.9 (0.4) years performed high intensity aerobic interval training sessions
      twice per week for 10 weeks in addition to normal soccer training. The specific
      aerobic training consisted of four sets of 4 min work periods dribbling a soccer
      ball around a specially designed track at 90-95% of maximal heart frequency, with
      a 3 min recovery jog at 70% of maximal heart frequency between intervals.
      RESULTS: Mean VO2max improved significantly from 63.4 (5.6) to 69.8 (6.6) ml kg(
      1) min(-1), or 183.3 (13.2) to 201.5 (16.2) ml kg(-0.75) min(-1) (p<0.001). Squat
      jump and counter movement jump height increased significantly from 37.7 (6.2) to
      40.3 (6.1) cm and 52.0 (4.0) to 53.4 (4.2) cm, respectively (p<0.05). No
      significant changes in body mass, running economy, rate of force development, or
      10 m sprint times occurred. CONCLUSION: Performing high intensity 4 min intervals
      dribbling a soccer ball around a specially designed track together with regular
      soccer training is effective for improving the VO2max of soccer players, with no
      negative interference effects on strength, jumping ability, and sprinting
      performance.

PMID- 15849291
TI  - Scale of protection and the various types of sports mouthguard.
AB  - OBJECTIVES: To present a grading system of the protection offered by various
      types of mouthguard, together with an indication of associated risks, in order to
      make athletes aware of the consequences of improper or no mouth protection.
      METHODS: A review of the literature on mouthguards, mouthguard materials, and
      novel laminates for mouthguards was carried out as it was apparent that
      information on mouthguards was lacking. Studies on stock (or unfitted)
      mouthguards, mouth formed (boil and bite) mouthguards, and custom mouthguards are
      reviewed. RESULTS: A scale of protection offered by various mouthguards and novel
      laminates has been produced, where 0 indicates no mouthguard and 10 indicates a
      custom made mouthguard offering excellent protection. CONCLUSIONS: From work
      carried out on laminates and the manufacturing processes of mouthguards, it
      became apparent that information was lacking to enable athletes make informed
      decisions about the best oral protection for their chosen sport.

PMID- 15849292
TI  - Low bone mineral density is two to three times more prevalent in non-athletic
      premenopausal women than in elite athletes: a comprehensive controlled study.
AB  - OBJECTIVE: To compare bone mineral density (BMD), investigate factors associated
      with BMD, and examine the prevalence of low BMD in athletes and non-athletic
      controls. METHODS: The study included a questionnaire (part I), measurement of
      BMD (part II), and a clinical interview (part III). All Norwegian female athletes
      on national teams (n = 938) and an aged matched random sample of non-athletic
      controls (n = 900) were invited to participate. The questionnaire was completed
      by 88% of athletes and 70% of controls. A random sample of these athletes (n =
      300) and controls (n = 300) was invited to participate in parts II and III. All
      parts were completed by 186 athletes (62%) and 145 controls (48%). RESULTS: Mean
      (standard deviation) total body (TB) BMD was higher (p<0.001) in athletes (1.21
      (0.09) g/cm2) than in controls (1.18 (0.08) g/cm2), and higher (p<0.001) in high
      impact (HI) sports athletes than in medium impact (MI) and low impact (LI) sports
      athletes. In athletes, body weight and impact loading sports were positively
      associated, and percent body fat and eating disorders were negatively associated
      with TB BMD. Body weight and weight bearing activities were positively associated
      and menstrual dysfunction was negatively associated with TB BMD in controls. A
      higher percentage of controls (28.3%) than athletes (10.7%) had low BMD
      (p<0.001). CONCLUSION: Female elite athletes have 3-20% higher BMD than non
      athletic controls and HI sports athletes have 3-22% higher BMD compared with MI
      and LI sports athletes. Low BMD is two to three times more common in non-athletic
      premenopausal women than in elite athletes.

PMID- 15849293
TI  - A prospective study of injuries and training amongst the England 2003 Rugby World
      Cup squad.
AB  - OBJECTIVES: To assess the aetiology, incidence, severity, and causes of injuries
      to England rugby union players during preparation for and participation in the
      2003 Rugby World Cup. METHOD: A 63 week prospective design was employed to study
      the training practices and injuries of England rugby players. The team physician
      reported all training and match injuries and provided details of the location,
      diagnosis, severity, and mechanism of each injury. The team fitness coach
      reported details of the number and duration of training sessions and the time
      dedicated to rugby and conditioning training. Players' stature, body mass, and
      skinfolds were measured at the beginning and end of the study period. RESULTS:
      The overall incidence of injury was 17 injuries/1000 h of exposure (match: 218
      injuries/1000 h; training: 6.1 injuries/1000 h). The major locations of injuries
      were the lower (60%) and upper (17%) limbs and the most common diagnoses were
      muscle and tendon (50%) and joint (non-bone) and ligament (41%) injuries. The
      highest incidences of match injuries occurred whilst being tackled (50
      injuries/1000 h) and in a ruck or maul (35 injuries/1000 h), whilst the greatest
      incidences of training injuries occurred during endurance running (24
      injuries/1000 h) and contact activities (20 injuries/1000 h). Players' average
      body mass increased and skinfold measurement decreased significantly over the
      study period. CONCLUSIONS: The incidence of match injuries at international level
      was found to be higher than previously reported. The tackle, ruck, and maul
      elements of match play and the endurance running and contact elements of training
      presented the highest risk of injury for all players.

PMID- 15849294
TI  - Reliability and validity of a brief physical activity assessment for use by
      family doctors.
AB  - OBJECTIVE: To evaluate the reliability and validity of a brief physical activity
      assessment tool suitable for doctors to use to identify inactive patients in the
      primary care setting. METHODS: Volunteer family doctors (n = 8) screened
      consenting patients (n = 75) for physical activity participation using a brief
      physical activity assessment tool. Inter-rater reliability was assessed within
      one week (n = 71). Validity was assessed against an objective physical activity
      monitor (computer science and applications accelerometer; n = 42). RESULTS: The
      brief physical activity assessment tool produced repeatable estimates of
      "sufficient total physical activity", correctly classifying over 76% of cases
      (kappa 0.53, 95% confidence interval (CI) 0.33 to 0.72). The validity coefficient
      was reasonable (kappa 0.40, 95% CI 0.12 to 0.69), with good percentage agreement
      (71%). CONCLUSIONS: The brief physical activity assessment tool is a reliable
      instrument, with validity similar to that of more detailed self report measures
      of physical activity. It is a tool that can be used efficiently in routine
      primary healthcare services to identify insufficiently active patients who may
      need physical activity advice.

PMID- 15849296
TI  - High prevalence of jumper's knee and sonographic changes in Swedish elite junior
      volleyball players compared to matched controls.
AB  - BACKGROUND: Jumper's knee is a common and troublesome condition among senior
      volleyball players, but its prevalence among elite junior players compared to
      matched non-sports active controls is not known. OBJECTIVE: To clinically, and by
      sonography, examine the patellar tendons in elite junior volleyball players (15
      19 years) at the Swedish National Centre for volleyball and in matched controls.
      METHODS: The patellar tendons in the 57 students at the Swedish National Centre
      for high school volleyball and in 55 age, height, and weight matched not
      regularly sports active controls were evaluated clinically and by grey scale
      ultrasonography (US) and power Doppler (PD) sonography. RESULTS: There were no
      significant differences in mean age, height, and weight between the volleyball
      players and the controls. In the volleyball group, jumper's knee was diagnosed
      clinically and by US in 12 patellar tendons (10 male and two female). In 12/12
      tendons, PD sonography demonstrated a neovascularisation in the area with
      structural tendon changes. In another 10 pain free tendons, there were structural
      tendon changes and neovessels. In the control group, no individual had a clinical
      diagnosis of jumper's knee. US demonstrated structural tendon changes in 11
      tendons, but there was no neovascularisation on PD sonography. CONCLUSIONS: A
      clinical diagnosis of jumper's knee, together with structural tendon changes and
      neovascularisation visualised with sonography, was seen among Swedish elite
      junior volleyball players but not in matched not regularly sports active
      controls. Structural tendon change alone was seen in 10% of the control tendons.

PMID- 15849297
TI  - Exercise over-stress and maximal muscle oxidative metabolism: a 31P magnetic
      resonance spectroscopy case report.
AB  - OBJECTIVE: 31P magnetic resonance spectroscopy (MRS) was used to document long
      lasting losses in muscle oxidative capacity after bouts of intense endurance
      exercise. METHODS: The subject was a 34 year old highly fit female cyclist
      (VO2MAX = 53.3 ml/kg/min). Over a five month period, she participated in three
      separate intense bouts of acute unaccustomed exercise. 31P MRS measurements were
      performed seven weeks after the first bout and every two weeks for 14 more weeks.
      In all cases, 31P MRS measurements followed three days after each bout. RESULTS:
      The subject showed a decreased ability to generate ATP from oxidative
      phosphorylation and an increased reliance on anaerobic ATP production during the
      70% and 100% maximal voluntary contractions after the exercise bouts. Increased
      rates of fatigue and increased indicators of exercise difficulty also accompanied
      these reductions in muscle oxidative capacity. Increased oxidative and anaerobic
      ATP production were needed to maintain the work level during a submaximal 45%
      maximal voluntary contraction exercise. CONCLUSIONS: Acute increases in intensity
      accompanied by a change in exercise mode can influence the ability of muscle to
      generate ATP. The muscles were less economical and required more ATP to generate
      force during the submaximal exercises. During the maximal exercises, the muscle's
      mitochondria showed a reduced oxidative capacity. However, these reductions in
      oxidative capacity at the muscle level were not associated with changes in whole
      body maximal oxygen uptake. Finally, these reductions in muscular oxidative
      capacity were accompanied by increased rates of anaerobic ATP production,
      fatigue, and indicators of exercise difficulty.

PMID- 15849298
TI  - Functional characterization and expression analysis of a gene, OsENT2, encoding
      an equilibrative nucleoside transporter in rice suggest a function in cytokinin
      transport.
AB  - We identified four genes for potential equilibrative nucleoside transporters
      (ENTs) from rice (Oryza sativa; designated OsENT1 through OsENT4). Growth
      analysis of budding yeast (Saccharomyces cerevisiae) cells expressing OsENTs
      showed that OsENT2 transported adenosine and uridine with high affinity
      (adenosine, K(m) = 3.0 microm; uridine, K(m) = 0.7 microm). Purine or pyrimidine
      nucleosides and 2'-deoxynucleosides strongly inhibited adenosine transport via
      OsENT2, suggesting that OsENT2 possesses broad substrate specificity. OsENT2
      mediated adenosine transport was resistant to the typical inhibitors of mammalian
      ENTs, nitrobenzylmercaptopurine ribonucleoside, dilazep, and dipyridamole. The
      transport activity was maximal at pH 5.0 and decreased slightly at lower as well
      as higher pH. In competition experiments with various cytokinins, adenosine
      transport by OsENT2 was inhibited by isopentenyladenine riboside (iPR). Direct
      measurements with radiolabeled cytokinins demonstrated that OsENT2 mediated
      uptake of iPR (K(m) = 32 microm) and trans-zeatin riboside (K(m) = 660 microm),
      suggesting that OsENT2 participates in iPR transport in planta. In mature plants,
      OsENT2 was predominantly expressed in roots. The OsENT2 promoter drove the
      expression of the beta-glucuronidase reporter gene in the scutellum during
      germination and in vascular tissues in germinated plants, suggesting a
      participation of OsENT2 in the retrieval of endosperm-derived nucleosides by the
      germinating embryo and in the long-distance transport of nucleosides in growing
      plants, respectively.

PMID- 15849299
TI  - Identification and characterization of endoplasmic reticulum-associated
      degradation proteins differentially affected by endoplasmic reticulum stress.
AB  - The disposal of misfolded proteins from the lumen of the endoplasmic reticulum
      (ER) is one of the quality control mechanisms present in the protein secretory
      pathway. Through ER-associated degradation, misfolded substrates are targeted to
      the cytosol where they are degraded by the proteasome. We have identified four
      maize (Zea mays) Der1-like genes (Zm Derlins) that encode homologs of Der1p, a
      yeast (Saccharomyces cerevisiae) protein implicated in ER-associated degradation.
      Zm Derlins are capable of functionally complementing a yeast Der1 deletion
      mutant. Such complementation indicates that the Der1p function is conserved among
      species. Zm Derlin genes are expressed at low levels throughout the plant, but
      appear prevalent in tissues with high activity of secretory protein accumulation,
      including developing endosperm cells. Expression of three of the four Zm Derlin
      genes increases during ER stress, with Zm Derlin1-1 showing the strongest
      induction. Subcellular fractionation experiments localized Zm Derlin proteins to
      the membrane fraction of microsomes. In maize endosperm, Zm Derlin proteins were
      found primarily associated with ER-derived protein bodies regardless of the
      presence of an ER stress response.

PMID- 15849300
TI  - The LPB1 gene is important for acclimation of Chlamydomonas reinhardtii to
      phosphorus and sulfur deprivation.
AB  - Organisms exhibit a diverse set of responses when exposed to low-phosphate
      conditions. Some of these responses are specific for phosphorus limitation,
      including responses that enable cells to efficiently scavenge phosphate from
      internal and external stores via the production of high-affinity phosphate
      transporters and the synthesis of intracellular and extracellular phosphatases.
      Other responses are general and occur under a number of different environmental
      stresses, helping coordinate cellular metabolism and cell division with the
      growth potential of the cell. In this article, we describe the isolation and
      characterization of a mutant of Chlamydomonas reinhardtii, low-phosphate
      bleaching (lpb1), which dies more rapidly than wild-type cells during phosphorus
      limitation. The responses of this mutant to nitrogen limitation appear normal,
      although the strain is also somewhat more sensitive than wild-type cells to
      sulfur deprivation. Interestingly, depriving the cells of both nutrients
      simultaneously allows for sustained survival that is similar to that observed
      with wild-type cells. Furthermore, upon phosphorus deprivation, the lpb1 mutant,
      like wild-type cells, exhibits increased levels of mRNA encoding the PHOX
      alkaline phosphatase, the PTB2 phosphate transporter, and the regulatory element
      PSR1. The mutant strain is also able to synthesize the extracellular alkaline
      phosphatase activity upon phosphorus deprivation and the arylsulfatase upon
      sulfur deprivation, suggesting that the specific responses to phosphorus and
      sulfur deprivation are normal. The LPB1 gene was tagged by insertion of the ARG7
      gene, which facilitated its isolation and characterization. This gene encodes a
      protein with strong similarity to expressed proteins in Arabidopsis (Arabidopsis
      thaliana) and predicted proteins in Oryza sativa and Parachlamydia. A domain in
      the protein contains some similarity to the superfamily of nucleotide-diphospho
      sugar transferases, and it is likely to be localized to the chloroplast or
      mitochondrion based on programs that predict subcellular localization. While the
      precise catalytic role and physiological function of the putative protein is not
      known, it may function in some aspect of polysaccharide metabolism and/or
      influence phosphorus metabolism (either structural or regulatory) in a way that
      is critical for allowing the cells to acclimate to nutrient limitation
      conditions.

PMID- 15849301
TI  - Mutants of Arabidopsis lacking a chloroplastic isoamylase accumulate
      phytoglycogen and an abnormal form of amylopectin.
AB  - Mutant lines defective for each of the four starch debranching enzyme (DBE) genes
      (AtISA1, AtISA2, AtISA3, and AtPU1) detected in the nuclear genome of Arabidopsis
      (Arabidopsis thaliana) were produced and analyzed. Our results indicate that both
      AtISA1 and AtISA2 are required for the production of a functional isoamylase-type
      of DBE named Iso1, the major isoamylase activity found in leaves. The absence of
      Iso1 leads to an 80% decrease in the starch content in both lines and to the
      accumulation of water-soluble polysaccharides whose structure is similar to
      glycogen. In addition, the residual amylopectin structure in the corresponding
      mutant lines displays a strong modification when compared to the wild type,
      suggesting a direct, rather than an indirect, function of Iso1 during the
      synthesis of amylopectin. Mutant lines carrying a defect in AtISA3 display a
      strong starch-excess phenotype at the end of both the light and the dark phases
      accompanied by a small modification of the amylopectin structure. This result
      suggests that this isoamylase-type of DBE plays a major role during starch
      mobilization. The analysis of the Atpu1 single-mutant lines did not lead to a
      distinctive phenotype. However, Atisa2/Atpu1 double-mutant lines display a 92%
      decrease in starch content. This suggests that the function of pullulanase partly
      overlaps that of Iso1, although its implication remains negligible when Iso1 is
      present within the cell.

PMID- 15849302
TI  - Sanguinarine biosynthesis is associated with the endoplasmic reticulum in
      cultured opium poppy cells after elicitor treatment.
AB  - Three key benzylisoquinoline alkaloid biosynthetic enzymes, (S)-N
      methylcoclaurine-3'-hydroxylase (CYP80B1), berberine bridge enzyme (BBE), and
      codeinone reductase (COR), were localized in cultured opium poppy (Papaver
      somniferum) cells by sucrose density gradient fractionation and immunogold
      labeling. CYP80B1 catalyzes the second to last step in the formation of (S)
      reticuline, the last common intermediate in sanguinarine and morphine
      biosynthesis. BBE converts (S)-reticuline to (S)-scoulerine as the first
      committed step in sanguinarine biosynthesis, and COR catalyzes the penultimate
      step in the branch pathway leading to morphine. Sanguinarine is an antimicrobial
      alkaloid that accumulates in the vacuoles of cultured opium poppy cells in
      response to elicitor treatment, whereas the narcotic analgesic morphine, which is
      abundant in opium poppy plants, is not produced in cultured cells. CYP80B1 and
      BBE were rapidly induced to high levels in response to elicitor treatment. By
      contrast, COR levels were constitutive in the cell cultures, but remained low and
      were not induced by addition of the elicitor. Western blots performed on protein
      homogenates from elicitor-treated cells fractionated on a sucrose density
      gradient showed the cosedimentation of CYP80B1, BBE, and sanguinarine with
      calreticulin, and COR with glutathione S-transferase. Calreticulin and
      glutathione S-transferase are markers for the endoplasmic reticulum (ER) and the
      cytosol, respectively. In response to elicitor treatment, large dilated vesicles
      rapidly developed from the lamellar ER of control cells and fused with the
      central vacuole. Immunogold localization supported the association of CYP80B1 and
      BBE with ER vesicles, and COR with the cytosol in elicitor-treated cells. Our
      results show that benzylisoquinoline biosynthesis and transport to the vacuole
      are associated with the ER, which undergoes major ultrastructural modification in
      response to the elicitor treatment of cultured opium poppy cells.

PMID- 15849303
TI  - Localization of soluble beta-carbonic anhydrase in the marine diatom
      Phaeodactylum tricornutum. Sorting to the chloroplast and cluster formation on
      the girdle lamellae.
AB  - A beta-carbonic anhydrase (CA) in the marine diatom Phaeodactylum tricornutum
      (PtCA1) is encoded by the nuclear genome. This enzyme was previously found to be
      important for the operation of photosynthesis with a high affinity for dissolved
      inorganic carbon. A cDNA sequence that encodes PtCA1 (ptca1) was shown to possess
      a presequence of 138 bp (pre138), which encodes an N-terminal sequence of 46
      amino acids (Pre46AA) that does not exist in the mature PtCA1. In this study,
      pre138 was ligated with the enhanced green fluorescent protein (GFP) gene (egfp),
      and introduced into P. tricornutum by microprojectile bombardment. Subsequently,
      the expressed Pre46AA-GFP fusion was shown to be localized in the chloroplast
      stroma, whereas the expressed GFP without Pre46AA was localized in the cytoplasm.
      Insertion of the DNA sequence, encoding a mature region of ptca1 (mptca1) between
      pre138 and egfp, resulted in the formation of particles with concentrated GFP
      fluorescence in the stroma of P. tricornutum. These particles, 0.3 to 3.0 mum in
      size, were shown to be distinct from the mitochondria and localized on the
      surface of the putative girdle lamella. The attachment of the initial one-half of
      the pre138 to the mptca1-egfp fusion caused the expressed GFP fusion to
      accumulate in areas surrounding the chloroplast, presumably due to the presence
      of the endoplasmic reticulum signal encoded by the initial half-sequence and to
      the absence of the chloroplast transit sequence. These results indicate that
      PtCA1 is targeted to the stroma by the bipartite sequences of Pre46AA and that
      the observed GFP particles are formed specifically in the stroma due to the
      function of the mptca1.

PMID- 15849304
TI  - Nematode infection triggers the de novo formation of unloading phloem that allows
      macromolecular trafficking of green fluorescent protein into syncytia.
AB  - Syncytial feeding complexes induced by the cyst nematode Heterodera schachtii
      represent strong metabolic sinks for photoassimilates. These newly formed
      structures were described to be symplastically isolated from the surrounding root
      tissue and their mechanism of carbohydrate import has repeatedly been under
      investigation. Here, we present analyses of the symplastic connectivity between
      the root phloem and these syncytia in nematode-infected Arabidopsis (Arabidopsis
      thaliana) plants expressing the gene of the green fluorescent protein (GFP) or of
      different GFP fusions under the control of the companion cell (CC)-specific
      AtSUC2 promoter. In the same plants, phloem differentiation during syncytium
      formation was monitored using cell-specific antibodies for CCs or sieve elements
      (SEs). Our results demonstrate that free, CC-derived GFP moved freely from the
      phloem into the syncytial domain. No or only marginal cell-to-cell passage of GFP
      was observed into other root cells adjacent to these syncytia. In contrast,
      membrane-anchored GFP variants as well as soluble GFP fusions with increased
      molecular masses were restricted to the SE-CC complex. The presented data also
      show that nematode infection triggers the de novo formation of phloem containing
      an approximately 3-fold excess of SEs over CCs. This newly formed phloem exhibits
      typical properties of unloading phloem previously described in other sink
      tissues. Our results reveal the existence of a symplastic pathway between phloem
      CCs and nematode-induced syncytia. The plasmodesmata responsible for this
      symplastic connectivity allow the cell-to-cell movement of macromolecules up to
      30 kD and are likely to represent the major or exclusive path for the supply of
      assimilates from the phloem into the syncytial complex.

PMID- 15849305
TI  - A novel short-root gene encodes a glucosamine-6-phosphate acetyltransferase
      required for maintaining normal root cell shape in rice.
AB  - Glycosylation is a posttranslational modification occurring in many secreted and
      membrane-associated proteins in eukaryotes. It plays important roles in both
      physiological and pathological processes. Most of these protein modifications
      depend on UDP-N-acetylglucosamine. In this study, a T-DNA insertional rice (Oryza
      sativa) mutant exhibiting a temperature-sensitive defect in root elongation was
      isolated. Genetic and molecular analysis indicated that the mutated phenotype was
      caused by loss of function of a gene encoding a glucosamine-6-P acetyltransferase
      (designated OsGNA1), which is involved in de novo UDP-N-acetylglucosamine
      biosynthesis. The aberrant root morphology of the gna1 mutant includes shortening
      of roots, disruption of microtubules, and shrinkage of cells in the root
      elongation zone. Our observations support the idea that protein glycosylation
      plays a key role in cell metabolism, microtubule stabilization, and cell shape in
      rice roots.

PMID- 15849306
TI  - Cloning and characterization of GLOSSY1, a maize gene involved in cuticle
      membrane and wax production.
AB  - The cuticle covering the aerial organs of land plants plays a protective role
      against several biotic and abiotic stresses and, in addition, participates in a
      variety of plant-insect interactions. Here, we describe the molecular cloning and
      characterization of the maize (Zea mays) GLOSSY1 (GL1) gene, a component of the
      pathway leading to cuticular wax biosynthesis in seedling leaves. The genomic and
      cDNA sequences we isolated differ significantly in length and in most of the
      coding region from those previously identified. The predicted GL1 protein
      includes three histidine-rich domains, the landmark of a family of membrane-bound
      desaturases/hydroxylases, including fatty acid-modifying enzymes. GL1 expression
      is not restricted to the juvenile developmental stage of the maize plant,
      pointing to a broader function of the gene product than anticipated on the basis
      of the mutant phenotype. Indeed, in addition to affecting cuticular wax
      biosynthesis, gl1 mutations have a pleiotropic effect on epidermis development,
      altering trichome size and impairing cutin structure. Of the many wax
      biosynthetic genes identified so far, only a few from Arabidopsis (Arabidopsis
      thaliana) were found to be essential for normal cutin formation. Among these is
      WAX2, which shares 62% identity with GL1 at the protein level. In wax2-defective
      plants, cutin alterations induce postgenital organ fusion. This trait is not
      displayed by gl1 mutants, suggesting a different role of the maize and
      Arabidopsis cuticle in plant development.

PMID- 15849307
TI  - Characterization and expression patterns of UDP-D-glucuronate decarboxylase genes
      in barley.
AB  - UDP-D-glucuronate decarboxylase (EC 4.1.1.35) catalyzes the synthesis of UDP-D
      xylose from UDP-D-glucuronate in an essentially irreversible reaction that is
      believed to commit glycosyl residues to heteroxylan and xyloglucan biosynthesis.
      Four members of the barley (Hordeum vulgare) UDP-D-glucuronate decarboxylase gene
      family, designated HvUXS1 to HvUXS4, have been cloned and characterized. Barley
      HvUXS1 appears to be a cytosolic enzyme, while the others are predicted to be
      membrane-bound proteins with single transmembrane helices. Heterologous
      expression of a barley HvUXS1 cDNA in Escherichia coli yields a soluble enzyme
      that converts UDP-d-glucuronate to UDP-D-xylose, is associated with a single
      molecule of bound NAD+, and is subject to feedback inhibition by UDP-D-xylose.
      Quantitative PCR shows that the HvUXS1 mRNA is most abundant among the 4 HvUXS
      genes, accounting for more than 80% of total HvUXS transcripts in most of the
      tissues examined. The abundance of HvUXS1 mRNA is 10-fold higher in mature roots
      and stems than in leaves, developing grains, or floral tissues. Transcriptional
      activities of HvUXS2 and HvUXS4 genes are relatively high in mature roots,
      coleoptiles, and stems compared with root tips, leaves, and floral tissues, while
      HvUXS3 mRNA is low in all tissues. In barley leaf sections, levels of the most
      abundant mRNA, encoding HvUXS1, reflect the amount of soluble enzymic protein and
      activity. In selected tissues where HvUXS1 transcript levels are high, cell walls
      have higher arabinoxylan contents.

PMID- 15849308
TI  - Genome-based examination of chlorophyll and carotenoid biosynthesis in
      Chlamydomonas reinhardtii.
AB  - The unicellular green alga Chlamydomonas reinhardtii is a particularly important
      model organism for the study of photosynthesis since this alga can grow
      heterotrophically, and mutants in photosynthesis are therefore conditional rather
      than lethal. The recently developed tools for genomic analyses of this organism
      have allowed us to identify most of the genes required for chlorophyll and
      carotenoid biosynthesis and to examine their phylogenetic relationships with
      homologous genes from vascular plants, other algae, and cyanobacteria.
      Comparative genome analyses revealed some intriguing features associated with
      pigment biosynthesis in C. reinhardtii; in some cases, there are additional
      conserved domains in the algal and plant but not the cyanobacterial proteins that
      may directly influence their activity, assembly, or regulation. For some steps in
      the chlorophyll biosynthetic pathway, we found multiple gene copies encoding
      putative isozymes. Phylogenetic studies, theoretical evaluation of gene
      expression through analysis of expressed sequence tag data and codon bias of each
      gene, enabled us to generate hypotheses concerning the function and regulation of
      the individual genes, and to propose targets for future research. We have also
      used quantitative polymerase chain reaction to examine the effect of low fluence
      light on the level of mRNA accumulation encoding key proteins of the biosynthetic
      pathways and examined differential expression of those genes encoding isozymes
      that function in the pathways. This work is directing us toward the exploration
      of the role of specific photoreceptors in the biosynthesis of pigments and the
      coordination of pigment biosynthesis with the synthesis of proteins of the
      photosynthetic apparatus.

PMID- 15849309
TI  - Antisense suppression of a (+)-delta-cadinene synthase gene in cotton prevents
      the induction of this defense response gene during bacterial blight infection but
      not its constitutive expression.
AB  - In cotton (Gossypium hirsutum) the enzyme (+)-delta-cadinene synthase (CDNS)
      catalyzes the first committed step in the biosynthesis of cadinane-type
      sesquiterpenes, such as gossypol, that provide constitutive and inducible
      protection against pests and diseases. A cotton cDNA clone encoding CDNS (cdn1
      C4) was isolated from developing embryos and functionally characterized. Southern
      analysis showed that CDNS genes belong to a large multigene family, of which five
      genomic clones were studied, including three pseudogenes and one gene that may
      represent another subfamily of CDNS. CDNS expression was shown to be induced in
      cotton infected with either the bacterial blight or verticillium wilt pathogens.
      Constructs for the constitutive or seed-specific antisense suppression of cdn1-C4
      were introduced into cotton by Agrobacterium-mediated transformation. Gossypol
      levels were not reduced in the seeds of transformants with either construct, nor
      was the induction of CDNS expression affected in stems of the constitutive
      antisense plants infected with Verticillium dahliae Kleb. However, the induction
      of CDNS mRNA and protein in response to bacterial blight infection of cotyledons
      was completely blocked in the constitutive antisense plants. These results
      suggest that cdn1-C4 may be involved specifically in the bacterial blight
      response and that the CDNS multigene family comprises a complex set of genes
      differing in their temporal and spatial regulation and responsible for different
      branches of the cotton sesquiterpene pathway.

PMID- 15849310
TI  - Spatial and temporal distribution of polyamine levels and polyamine anabolism in
      different organs/tissues of the tobacco plant. Correlations with age, cell
      division/expansion, and differentiation.
AB  - Polyamine (PA) titers and biosynthesis follow a basipetal decrease along the
      tobacco (Nicotiana tabacum) plant axis, and they also correlate negatively with
      cell size. On the contrary, the titers of arginine (Arg), ornithine (Orn), and
      arginase activity increase with age. The free (soluble)/total-PA ratios gradually
      increase basipetally, but the soluble conjugated decrease, with spermidine (Spd)
      mainly to determine these changes. The shoot apical meristems are the main site
      of Spd and spermine biosynthesis, and the hypogeous tissues synthesize mostly
      putrescine (Put). High and low Spd syntheses are correlated with cell division
      and expansion, respectively. Put biosynthetic pathways are differently regulated
      in hyper- and hypogeous tobacco tissues: Only Arg decarboxylase is responsible
      for Put synthesis in old hypergeous vascular tissues, whereas, in hypogeous
      tissues, arginase-catalyzed Orn produces Put via Orn decarboxylase. Furthermore,
      Orn decarboxylase expression coincides with early cell divisions in marginal
      sectors of the lamina, and Spd synthase strongly correlates with later cell
      divisions in the vascular regions. This detailed spatial and temporal profile of
      the free, soluble-conjugated, and insoluble-conjugated fractions of Put, Spd, and
      spermine in nearly all tobacco plant organs and the profile of enzymes of PA
      biosynthesis at the transcript, protein, and specific activity levels, along with
      the endogenous concentrations of the precursor amino acids Arg and Orn, offer new
      insight for further understanding the physiological role(s) of PAs. The results
      are discussed in the light of age dependence, cell division/expansion,
      differentiation, phytohormone gradients, senescence, and sink-source
      relationships.

PMID- 15849311
TI  - Ethylene-regulated floral volatile synthesis in petunia corollas.
AB  - In many flowering plants, such as petunia (Petunia x hybrida), ethylene produced
      in floral organs after pollination elicits a series of physiological and
      biochemical events, ultimately leading to senescence of petals and successful
      fertilization. Here, we demonstrate, using transgenic ethylene insensitive
      (44568) and Mitchell Diploid petunias, that multiple components of emission of
      volatile organic compounds (VOCs) are regulated by ethylene. Expression of
      benzoic acid/salicylic acid carboxyl methyltransferase (PhBSMT1 and 2) mRNA is
      temporally and spatially down-regulated in floral organs in a manner consistent
      with current models for post-pollination ethylene synthesis in petunia corollas.
      Emission of methylbenzoate and other VOCs after pollination and exogenous
      ethylene treatment parallels a reduction in PhBSMT1 and 2 mRNA levels. Under
      cyclic light conditions (day/night), PhBSMT mRNA levels are rhythmic and precede
      emission of methylbenzoate by approximately 6 h. When shifted into constant dark
      or light conditions, PhBSMT mRNA levels and subsequent methylbenzoate emission
      correspondingly decrease or increase to minimum or maximum levels observed during
      normal conditions, thus suggesting that light may be a more critical influence on
      cyclic emission of methylbenzoate than a circadian clock. Transgenic PhBSMT RNAi
      flowers with reduced PhBSMT mRNA levels show a 75% to 99% decrease in
      methylbenzoate emission, with minimal changes in other petunia VOCs. These
      results implicate PhBSMT1 and 2 as genes responsible for synthesis of
      methylbenzoate in petunia.

PMID- 15849312
TI  - Surface plasmon field-enhanced fluorescence spectroscopy studies of primer
      extension reactions.
AB  - Surface plasmon field-enhanced fluorescence spectroscopy (SPFS) utilizes the
      evanescent electromagnetic field of a surface plasmon to excite chromophors in
      close proximity to the surface. While conventional surface plasmon resonance
      spectroscopy allows the observation of surface reactions by means of refractive
      index changes, SPFS additionally provides a channel for the read-out of
      fluorescence changes. Thus, the detection limit for low mass compounds, whose
      adsorption is only accompanied by small refractive index changes, can be
      substantially improved by fluorescent labeling. In this study, we present the
      first example that utilizes SPFS to follow the dynamics of an enzymatic reaction.
      The elongation of surface-tethered DNA has been observed by the incorporation of
      Cy5-labeled nucleotides into the nascent strand by the action of DNA polymerase I
      (Klenow fragment). The technique offers a rapid way to determine the binding
      constant and the catalytic activity of a DNA processing enzyme, here exemplified
      by the Klenow fragment. Furthermore, the effect of mispaired bases in the
      primer/template duplex and the influence of different label densities have been
      studied. The resulting sensitivity for nucleotide incorporation, being in the
      femtomolar regime, combined with the specificity of the enzyme for fully
      complementary DNA duplexes suggest the application of this assay as a powerful
      tool for DNA detection.

PMID- 15849313
TI  - The repressor DREAM acts as a transcriptional activator on Vitamin D and retinoic
      acid response elements.
AB  - DREAM (downstream regulatory element antagonist modulator) is a transcriptional
      repressor, which binds DREs (downstream response elements) in a Ca2+-regulated
      manner. The DREs consist of core GTCA motifs, very similar to binding motifs for
      non-steroid nuclear receptors. In this work, we find that DREAM stimulates basal
      and ligand-dependent activation of promoters containing vitamin D and retinoic
      acid response elements (VDREs and RAREs), consisting of direct repeats of the
      sequence AGT/GTCA spaced by 3 or 5 nt, respectively. Stimulation occurs when the
      element is located upstream, but not downstream, the transcription initiation
      site. Activation requires both Ca2+ binding to the EF-hands and the leucine
      charged domains (LCDs), analogous to those responsible for the interaction of the
      nuclear receptors with coregulators. Further more, DREAM can bind both 'in vitro'
      and in chromatin immunoprecipitation assays to these elements. Importantly, 'in
      vivo' binding is only observed in vitamin D- or RA-treated cells. These results
      show that DREAM can function as an activator of transcription on certain
      promoters and demonstrate a novel role for DREAM acting as a potential modulator
      of genes containing binding sites for nuclear receptors.

PMID- 15849314
TI  - Influence of RNA structural stability on the RNA chaperone activity of the
      Escherichia coli protein StpA.
AB  - Proteins with RNA chaperone activity are able to promote folding of RNA molecules
      by loosening their structure. This RNA unfolding activity is beneficial when
      resolving misfolded RNA conformations, but could be detrimental to RNAs with low
      thermodynamic stability. In order to test this idea, we constructed various RNAs
      with different structural stabilities derived from the thymidylate synthase (td)
      group I intron and measured the effect of StpA, an Escherichia coli protein with
      RNA chaperone activity, on their splicing activity in vivo and in vitro. While
      StpA promotes splicing of the wild-type td intron and of mutants with wild-type
      like stability, splicing of mutants with a lower structural stability is reduced
      in the presence of StpA. In contrast, splicing of an intron mutant, which is not
      destabilized but which displays a reduced population of correctly folded RNAs, is
      promoted by StpA. The sensitivity of an RNA towards StpA correlates with its
      structural stability. By lowering the temperature to 25 degrees C, a temperature
      at which the structure of these mutants becomes more stable, StpA is again able
      to stimulate splicing. These observations clearly suggest that the structural
      stability of an RNA determines whether the RNA chaperone activity of StpA is
      beneficial to folding.

PMID- 15849315
TI  - Computational technique for improvement of the position-weight matrices for the
      DNA/protein binding sites.
AB  - Position-weight matrices (PWMs) are broadly used to locate transcription factor
      binding sites in DNA sequences. The majority of existing PWMs provide a low level
      of both sensitivity and specificity. We present a new computational algorithm, a
      modification of the Staden-Bucher approach, that improves the PWM. We applied the
      proposed technique on the PWM of the GC-box, binding site for Sp1. The comparison
      of old and new PWMs shows that the latter increase both sensitivity and
      specificity. The statistical parameters of GC-box distribution in promoter
      regions and in the human genome, as well as in each chromosome, are presented.
      The majority of commonly used PWMs are the 4-row mononucleotide matrices,
      although 16-row dinucleotide matrices are known to be more informative. The
      algorithm efficiently determines the 16-row matrices and preliminary results show
      that such matrices provide better results than 4-row matrices.

PMID- 15849316
TI  - TM-align: a protein structure alignment algorithm based on the TM-score.
AB  - We have developed TM-align, a new algorithm to identify the best structural
      alignment between protein pairs that combines the TM-score rotation matrix and
      Dynamic Programming (DP). The algorithm is approximately 4 times faster than CE
      and 20 times faster than DALI and SAL. On average, the resulting structure
      alignments have higher accuracy and coverage than those provided by these most
      often-used methods. TM-align is applied to an all-against-all structure
      comparison of 10 515 representative protein chains from the Protein Data Bank
      (PDB) with a sequence identity cutoff <95%: 1996 distinct folds are found when a
      TM-score threshold of 0.5 is used. We also use TM-align to match the models
      predicted by TASSER for solved non-homologous proteins in PDB. For both folded
      and misfolded models, TM-align can almost always find close structural analogs,
      with an average root mean square deviation, RMSD, of 3 A and 87% alignment
      coverage. Nevertheless, there exists a significant correlation between the
      correctness of the predicted structure and the structural similarity of the model
      to the other proteins in the PDB. This correlation could be used to assist in
      model selection in blind protein structure predictions. The TM-align program is
      freely downloadable at http://bioinformatics.buffalo.edu/TM-align.

PMID- 15849317
TI  - Inhibition of archaeal growth and DNA topoisomerase VI activities by the Hsp90
      inhibitor radicicol.
AB  - Type II DNA topoisomerases have been classified into two families, Topo IIA and
      Topo IIB, based on structural and mechanistic dissimilarities. Topo IIA is the
      target of many important antibiotics and antitumoural drugs, most of them being
      inactive on Topo IIB. The effects and mode of action of Topo IIA inhibitors in
      vitro and in vivo have been extensively studied for the last twenty-five years.
      In contrast, studies of Topo IIB inhibitors were lacking. To document this field,
      we have studied two Hsp90 inhibitors (radicicol and geldanamycin), known to
      interact with the ATP-binding site of Hsp90 (the Bergerat fold), which is also
      present in Topo IIB. Here, we report that radicicol inhibits the decatenation and
      relaxation activities of Sulfolobus shibatae DNA topoisomerase VI (a Topo IIB)
      while geldanamycin does not. In addition, radicicol has no effect on the Topo IIA
      Escherichia coli DNA gyrase. In agreement with their different effects on DNA
      topoisomerase VI, we found that radicicol can theoretically fit in the ATP
      binding pocket of the DNA topoisomerase VI 'Bergerat fold', whereas geldanamycin
      cannot. Radicicol inhibited growths of Sulfolobus acidocaldarius (a crenarchaeon)
      and of Haloferax volcanii (a euryarchaeon) at the same doses that inhibited DNA
      topoisomerase VI in vitro. In contrast, the bacteria E.coli was resistant to this
      drug. Radicicol thus appears to be a very promising compound to study the
      mechanism of Topo IIB in vitro, as well as the biological roles of these enzymes
      in vivo.

PMID- 15849319
TI  - High frequency trans-splicing in a cell line producing spliced and polyadenylated
      RNA polymerase I transcripts from an rDNA-myc chimeric gene.
AB  - The 2G1MycP2Tu1 cell line was obtained following transfection of human colon
      carcinoma cells from the SW613-S cell line with a plasmid carrying a genomic copy
      of the human MYC gene. 2G1MycP2Tu1 cells produce MYC mRNAs and proteins of
      abnormal size. In order to analyze the structure of these abnormal products, a
      cDNA library constructed using RNA isolated from these cells was screened with a
      MYC probe. Fifty clones were studied by DNA sequencing. The results indicated
      that a truncated copy of the MYC gene had integrated into an rDNA transcription
      unit in 2G1MycP2Tu1 cells. This was confirmed by northern blot analysis, PCR
      amplification on genomic DNA and fluorescent in situ hybridization (FISH)
      experiments on metaphase chromosomes. 2G1MycP2Tu1 cells produce hybrid rRNA-MYC
      RNA molecules that are polyadenylated and processed by splicing reactions
      involving natural and cryptic splice sites. These transcripts are synthesized by
      RNA polymerase I, as confirmed by actinomycin D sensitivity experiments,
      suggesting that 3' end processing and splicing are uncoupled from transcription
      in this case. 2G1MycP2Tu1 cells also produce another type of chimeric mRNAs
      consisting of correctly spliced exons 2 and 3 of the MYC gene fused to one or
      more extraneous 5' exons by proper splicing to the acceptor sites of MYC exon 2.
      These foreign exons belong to 33 different genes, which are located on 14
      different chromosomes. These observations and the results of FISH and Southern
      blotting experiments lead us to conclude that trans-splicing events occur at high
      frequency in 2G1MycP2Tu1 cells.

PMID- 15849320
TI  - Bacillus subtilis RecN binds and protects 3'-single-stranded DNA extensions in
      the presence of ATP.
AB  - Bacillus subtilis RecN appears to be an early detector of breaks in double
      stranded DNA. In vivo, RecN forms discrete nucleoid-associated structures and in
      vitro exhibits Mg2+-dependent single-stranded (ss) DNA binding and ssDNA
      dependent ATPase activities. In the presence of ATP or ADP, RecN assembles to
      form large networks with ssDNA molecules (designated complexes CII and CIII) that
      involve ATP binding and requires a 3'-OH at the end of ssDNA molecule. Addition
      of dATP-RecA complexes dissociates RecN from these networks, but this is not
      observed following addition of an ssDNA binding protein. Apparently, ATP
      modulates the RecN-ssDNA complex for binding to ssDNA extensions and, in vivo,
      RecN-ATP bound to 3'-ssDNA might sequester ssDNA ends within complexes that
      protect the ssDNA while the RecA accessory proteins recruit RecA. With the
      association of RecA to ssDNA, RecN would dissociate from the DNA end facilitating
      the subsequent steps in DNA repair.

PMID- 15849318
TI  - COUP-TF interacting protein 2 represses the initial phase of HIV-1 gene
      transcription in human microglial cells.
AB  - Human immunodeficiency virus type 1 (HIV-1) gene transcription is characterized
      by two temporally distinct phases. While the initial phase relies solely on
      cellular transcription factors, the subsequent phase is activated by the viral
      Tat transactivator. We have previously reported that the subsequent phase of
      viral gene transcription can be repressed by the chicken ovalbumin upstream
      promoter transcription factor (COUP-TF)-interacting protein 2 (CTIP2) in human
      microglial cells [O. Rohr, D. Lecestre, S. Chasserot-Golaz, C. Marban, D. Avram,
      D. Aunis, M. Leid and E. Schaeffer (2003), J. Virol., 77, 5415-5427]. Here, we
      demonstrate that CTIP proteins also repress the initial phase of HIV-1 gene
      transcription, mainly supported by the cellular transcription factors Sp1 and
      COUP-TF in microglial cells. We report that CTIP2 represses Sp1- and COUP-TF
      mediated activation of HIV-1 gene transcription and viral replication as a result
      of physical interactions with COUP-TF and Sp1 in microglial nuclei. Using laser
      confocal microscopy CTIP2 was found to colocalize with Sp1, COUP-TF and the
      heterochromatin-associated protein Hp1alpha, which is mainly detected in
      transcriptionally repressed heterochromatic region. Moreover, we describe that
      CTIP2 can be recruited to the HIV-1 promoter via its association with Sp1 bound
      to the GC-box sequences of the long terminal repeat (LTR). Since our findings
      demonstrate that CTIP2 interacts with the HIV-1 proximal promoter, it is likely
      that CTIP2 promotes HIV-1 gene silencing by forcing transcriptionally repressed
      heterochromatic environment to the viral LTR region.

PMID- 15849323
TI  - Severe asthma in adults.
AB  - Severe asthma remains poorly understood and frustrating to care for, partly
      because it is a heterogeneous disease. Patients with severe asthma
      disproportionately consume health care resources related to asthma. Severe asthma
      may develop over time, or shortly after onset of the disease. The genetic and
      environmental elements that may be most important in the development of severe
      disease are poorly understood, but likely include both allergic and nonallergic
      elements. Physiologically, these patients often have air trapping, airway
      collapsibility, and a high degree of methacholine hyperresponsiveness. Specific
      phenotypes of severe asthma are only beginning to be defined. However, describing
      severe asthma by age at onset (early- vs. late-onset) appears to describe two
      phenotypes that differ at immunologic, physiologic, epidemiologic, and pathologic
      levels. In particular, early-onset severe asthma is a more allergic-associated
      disease than late-onset severe asthma. In addition, patients with severe asthma
      can be defined on the basis of presence and type of inflammation. Severe asthma
      with persistent eosinophilia (of either early or late onset) is more symptomatic
      and has more near-fatal events. However, at least 50% of patients with severe
      asthma have very little identifiable inflammation. Thus, "steroid resistance" may
      occur at numerous levels, not all of which are caused by a lack of effect of
      steroids on inflammation. Treatment remains problematic, with corticosteroids
      remaining the most effective therapy. However, 5-lipoxygenase inhibitors, anti
      IgE, and immunomodulatory drugs are also likely to have a place in treatment.
      Improving therapy in this disease will require a better understanding of the
      phenotypes involved.

PMID- 15849325
TI  - Requirement for leukotriene B4 receptor 1 in allergen-induced airway
      hyperresponsiveness.
AB  - RATIONALE: Leukotriene B4 (LTB4) is a rapidly synthesized, early leukocyte
      chemoattractant that signals via its cell surface receptor, leukotriene B4
      receptor 1 (BLT1), to attract and activate leukocytes during inflammation. A role
      for the LTB4-BLT1 pathway in allergen-induced airway hyperresponsiveness and
      inflammation is not well defined. OBJECTIVES: To define the role of the LTB4
      receptor (BLT1) in the development of airway inflammation and altered airway
      function. METHODS: BLT1-deficient (BLT1 -/-) mice and wild-type mice were
      sensitized to ovalbumin by intraperitoneal injection and then challenged with
      ovalbumin via the airways. Airway responsiveness to inhaled methacholine,
      bronchoalveolar lavage fluid cell composition and cytokine levels, and lung
      inflammation and goblet cell hyperplasia were assessed. RESULTS: Compared with
      wild-type mice, BLT1 -/- mice developed significantly lower airway responsiveness
      to inhaled methacholine, lower goblet cell hyperplasia in the airways, and
      decreased interleukin (IL)-13 production both in vivo, in the bronchoalveolar
      lavage fluid, and in vitro, after antigen stimulation of lung cells in culture.
      Intracellular cytokine staining of lung cells revealed that bronchoalveolar
      lavage IL-13 levels and numbers of IL-13(+)/CD4+ and IL-13(+)/CD8+ T cells were
      also reduced in BLT1 -/- mice. Reconstitution of sensitized and challenged BLT1 
      /- mice with allergen-sensitized BLT1 +/+ T cells fully restored the development
      of airway hyperresponsiveness. In contrast, transfer of naive T cells failed to
      do so. CONCLUSION: These data suggest that BLT1 expression on primed T cells is
      required for the full development of airway hyperresponsiveness, which appears to
      be associated with IL-13 production in these cells.

PMID- 15849324
TI  - Diaphragm dysfunction in chronic obstructive pulmonary disease.
AB  - RATIONALE: Hypercapnic respiratory failure because of inspiratory muscle weakness
      is the most important cause of death in chronic obstructive pulmonary disease
      (COPD). However, the pathophysiology of failure of the diaphragm to generate
      force in COPD is in part unclear. OBJECTIVES: The present study investigated
      contractile function and myosin heavy chain content of diaphragm muscle single
      fibers from patients with COPD. METHODS: Skinned muscle fibers were isolated from
      muscle biopsies from the diaphragm of eight patients with mild to moderate COPD
      and five patients without COPD (mean FEV(1) % predicted, 70 and 100%,
      respectively). Contractile function of single fibers was assessed, and
      afterwards, myosin heavy chain content was determined in these fibers. In
      diaphragm muscle homogenates, the level of ubiquitin-protein conjugation was
      determined. RESULTS: Diaphragm muscle fibers from patients with COPD showed
      reduced force generation per cross-sectional area, and reduced myosin heavy chain
      content per half sarcomere. In addition, these fibers had decreased Ca2+
      sensitivity of force generation, and slower cross-bridge cycling kinetics. Our
      observations were present in fibers expressing slow and 2A isoforms of myosin
      heavy chain. Ubiquitin-protein conjugation was increased in diaphragm muscle
      homogenates of patients with mild to moderate COPD. CONCLUSIONS: Early in the
      development of COPD, diaphragm fiber contractile function is impaired. Our data
      suggest that enhanced diaphragm protein degradation through the ubiquitin
      proteasome pathway plays a role in loss of contractile protein and, consequently,
      failure of the diaphragm to generate force.

PMID- 15849326
TI  - Primum non nocere: does the current research publication system (or the lay
      press) harm our patients?

PMID- 15849327
TI  - Charting (and publishing) the boundaries of critical illness.

PMID- 15849328
TI  - Is idiopathic pulmonary fibrosis now treatable?

PMID- 15849329
TI  - One hundred years of chronic obstructive pulmonary disease.

PMID- 15849330
TI  - The GOAL study: designed to favor a long-acting beta2-agonist?

PMID- 15849339
TI  - Seeking the truth: the evidence-based approach to veterinary medicine.

PMID- 15849331
TI  - An own GOAL or a real breakthrough?

PMID- 15849342
TI  - Comparison of the efficacy of a synthetic dog-appeasing pheromone with
      clomipramine for the treatment of separation-related disorders in dogs.
AB  - Sixty-seven dogs that showed signs of distress when separated from their owners
      (destructiveness, excessive vocalisation and house soiling) and hyperattachment
      were used in a randomised, blind trial to assess the potential value of a dog
      appeasing pheromone in reducing the unacceptable behaviours. For ethical reasons,
      there was no placebo group and the effects of the pheromone were compared with
      the effects of clomipramine which is regularly used to treat this type of
      problem. The undesirable behaviours decreased in both groups, but the overall
      assessment by the owners indicated that there was no significant difference
      between the two treatments, although there were fewer undesirable events in the
      dogs treated with the pheromone, and the administration of the pheromone appeared
      to be more convenient.

PMID- 15849343
TI  - Effects of surgery on the acute phase response in clinically normal and diseased
      horses.
AB  - The serum concentrations of serum amyloid A, haptoglobin and fibrinogen were
      measured in a group of horses before and at intervals after elective and non
      elective surgery, and in a control group of normal horses. There was a
      significant, rapid and repeatable increase in the concentration of serum amyloid
      A in response to both elective and non-elective surgery. In the control horses
      its serum concentration was within the normal range, from 0 to 0.2 microg/ml.
      Twenty-four hours after elective surgery its mean peak concentration was 16.4
      microg/ml, and after non-elective surgery it was 27.3 microg/ml. In contrast, the
      serum concentrations of haptoglobin and fibrinogen increased more slowly after
      surgery and had not decreased by 72 hours after surgery.

PMID- 15849344
TI  - Two cases of feline leishmaniosis in Switzerland.
AB  - Two cats with Leishmania species infections were investigated. The first had been
      imported from Spain with a non-healing, ulcerated nodule on a hindleg. The
      presence of Leishmania species was detected by histopathology and pcr on samples
      of skin. The lesion was unresponsive to treatment with allopurinol for three
      months but the cat was treated successfully by removing the lesion surgically.
      The second cat had lived in both Spain and Switzerland, and had a history of
      recurrent skin lesions on its head and neck. A diagnosis of pemphigus foliaceus
      was made on the basis of histopathology, but Leishmania species serology (elisa)
      and pcr of skin were positive, leading to a diagnosis of a Leishmania species
      infection combined with pemphigus foliaceus.

PMID- 15849345
TI  - Resistance of immature bovine oocytes to non-cytopathogenic bovine viral
      diarrhoea virus in vitro.

PMID- 15849346
TI  - Progression of Q fever and Coxiella burnetii shedding in milk after an outbreak
      of enzootic abortion in a goat herd.

PMID- 15849347
TI  - Nucleotide and amino acid sequence analysis of a birnavirus isolated from
      penguins.

PMID- 15849348
TI  - Malignant, solitary, nasopharyngeal schwannoma in a cow.

PMID- 15849349
TI  - Phenylbutazone and equine research.

PMID- 15849350
TI  - Bovine TB and badgers.

PMID- 15849351
TI  - Society of Women Veterinary Surgeons' Trust.

PMID- 15849352
TI  - Logos for the RCVS Practice Standards Scheme.

PMID- 15849353
TI  - Bovine TB and badgers.

PMID- 15849354
TI  - Distinct structural features of phospholipids differentially determine ethanol
      sensitivity and basal function of BK channels.
AB  - Large conductance Ca2+ -activated K+ (BK) channel activity and its potentiation
      by ethanol are both critically modulated by bilayer phosphatidylserine (PS), a
      phospholipid involved in membrane-bound signaling. Whether PS is uniquely
      required for ethanol to modify channel activity is unknown. Furthermore, the
      structural determinants in membrane phospholipid molecules that control alcohol
      action remain to be elucidated. We addressed these questions by reconstituting BK
      channels from human brain (hslo) into bilayers that contained phospholipids
      differing in headgroup size, charge, and acyl chain saturation. Data demonstrate
      that ethanol potentiation of hslo channels is blunted by conical phospholipids
      but favored by cylindrical phospholipids, independently of phospholipid charge.
      As found with ethanol action, basal channel activity is higher in bilayers
      containing cylindrical phospholipids. Basal activity and its ethanol potentiation
      in bilayers containing phosphatidylcholine, however, are not as robust as in
      those containing PS. These results are best interpreted as resulting from the
      relief of bilayer stress caused by inclusion of cylindrical phospholipids, with
      this relief being synergistically evoked by molecular shape and negative
      headgroup charge. Present findings suggest that hslo gating structures targeted
      by ethanol are accessible to sense changes in bilayer stress. In contrast, hslo
      unitary conductance is significantly higher in bilayers that contain negatively
      charged phospholipids independently of molecular shape, a result that is likely
      to be dependent on an interaction between anionic phospholipids and deep channel
      residues coupled to the selectivity filter.

PMID- 15849355
TI  - Resveratrol inhibits angiotensin II- and epidermal growth factor-mediated Akt
      activation: role of Gab1 and Shp2.
AB  - trans-Resveratrol (RV), a polyphenolic stilbene derivative found in grape skin
      and other food products, has been proposed to exert beneficial effects in
      cardiovascular disease. Our group has shown previously that RV inhibits
      angiotensin II (Ang II)-induced Akt activation and, consequently, vascular smooth
      muscle cell (VSMC) hypertrophy. In this work, to identify the molecular target of
      RV, we investigated the impact of RV on early signaling cascades in rat aortic
      VSMCs triggered by Ang II and epidermal growth factor (EGF). We show that RV does
      not influence Ang II-mediated transactivation of EGF-receptor but potently
      inhibits EGF-induced phosphorylation of Akt kinase, suggesting that RV acts
      downstream of EGF-receptor transactivation in VSMCs. Recent evidence indicates
      that the adapter molecule Gab1, together with the protein tyrosine phosphatase
      Shp2, is critically involved in regulating the strength and duration of
      phosphatidylinositol-3-kinase (PI3K) and Akt activation upon EGF stimulation in
      fibroblasts. Our results show that stimulation of VSMCs with EGF as well as Ang
      II leads to a rapid tyrosine phosphorylation of Gab1 and its association with the
      p85 subunit of PI3K. RV attenuates these processes. Experiments performed in Shp2
      deficient fibroblasts revealed that RV does not inhibit EGF-stimulated Akt
      activation in these cells, suggesting that Shp2 is necessary for the inhibitory
      effect of RV on the PI3K/Akt pathway. Furthermore, RV treatment activates Shp2.
      We therefore propose that RV blocks Akt activation in Ang II- and EGF-stimulated
      VSMCs by activating Shp2, thus preventing interaction between Gab1 and PI3K that
      is necessary for further signal transduction.

PMID- 15849356
TI  - Identification of a novel recognition sequence for fibronectin within the NH2
      terminal beta-sandwich domain of tissue transglutaminase.
AB  - Tissue transglutaminase belongs to the multigene transglutaminase family of Ca2+
      dependent protein cross-linking enzymes. Unlike other transglutaminases, it is
      involved in cell-matrix interactions and serves as an adhesion co-receptor for
      fibronectin. Previous work established that the fibronectin-binding motif(s) is
      located within the NH2-terminal proteolytic fragment of the protein consisting of
      residues 1-272. Here we identify a novel fibronectin recognition site within this
      sequence of tissue transglutaminase. Substitution of individual domains of tissue
      transglutaminase with those from homologous factor XIIIA showed that the major
      fibronectin-binding site is present within the first beta-sandwich domain of the
      protein. Experiments with deletion mutants of the first domain revealed that
      amino acids 81-140 of tissue transglutaminase are involved in fibronectin
      binding. Using synthetic peptides encompassing this region, we found that the
      peptide 88WTATVVDQQDCTLSLQLTT106 inhibited the interaction of tissue
      transglutaminase with fibronectin and decreased transglutaminase-dependent cell
      adhesion and spreading. In the three-dimensional structure of the first domain,
      amino acids 88-106 comprise an extended hairpin formed by antiparallel beta
      strands 5 and 6. Mutations of Asp94 and Asp97 within the beta5/beta6 hairpin to
      Ala significantly reduced the affinity of tissue transglutaminase for
      fibronectin, indicating that these residues are critical for fibronectin binding.
      Identification of the fibronectin-binding site on tissue transglutaminase will
      help to dissect the role of this protein in cell-matrix interactions.

PMID- 15849357
TI  - Interactive sites in the MyD88 Toll/interleukin (IL) 1 receptor domain
      responsible for coupling to the IL1beta signaling pathway.
AB  - Myeloid differentiation factor MyD88 is the essential adaptor protein that
      integrates and transduces intracellular signals generated by multiple Toll-like
      receptors including receptor complex for interleukin (IL) 1beta, a key
      inflammatory cytokine. IL1beta receptor complex interacts with MyD88 via the
      Toll/IL1 receptor (TIR) domain. Here we report structure-function studies that
      help define the MyD88 TIR domain binding sites involved in IL1beta-induced
      protein-protein interactions. The MyD88 TIR domain, employed as a dominant
      negative inhibitor of IL1beta signaling to screen MyD88 TIR mutants, lost its
      suppressing activity upon truncation of its Box 3. Accordingly, mutations of Box
      3 residues 285-286 reversed the dominant negative effect of the MyD88 TIR domain
      on IL1beta-induced and NFkappaB-dependent reporter gene activity and IL6
      production. Moreover, mutations of residues 171 in helix alphaA, 195-197 in Box
      2, and 275 in betaE-strand had similar functional effects. Strikingly, only
      mutations of residues 195-197 eliminated the TIR-TIR interaction of MyD88 and IL1
      receptor accessory protein (IL1RAcP), whereas substitution of neighboring
      canonical Pro200 by His was without effect. Mutations in Box 2 and 3 prevented
      homotypic MyD88 oligomerization via TIR domain. Based on this structure-function
      analysis, a three-dimensional docking model of TIR-TIR interaction between MyD88
      and IL1RAcP was developed.

PMID- 15849358
TI  - Oxygen tolerance of the H2-sensing [NiFe] hydrogenase from Ralstonia eutropha H16
      is based on limited access of oxygen to the active site.
AB  - Hydrogenases, abundant proteins in the microbial world, catalyze cleavage of H2
      into protons and electrons or the evolution of H2 by proton reduction. Hydrogen
      metabolism predominantly occurs in anoxic environments mediated by hydrogenases,
      which are sensitive to inhibition by oxygen. Those microorganisms, which thrive
      in oxic habitats, contain hydrogenases that operate in the presence of oxygen. We
      have selected the H2-sensing regulatory [NiFe] hydrogenase of Ralstonia eutropha
      H16 to investigate the molecular background of its oxygen tolerance. Evidence is
      presented that the shape and size of the intramolecular hydrophobic cavities
      leading to the [NiFe] active site of the regulatory hydrogenase are crucial for
      oxygen insensitivity. Expansion of the putative gas channel by site-directed
      mutagenesis yielded mutant derivatives that are sensitive to inhibition by
      oxygen, presumably because the active site has become accessible for oxygen. The
      mutant proteins revealed characteristics typical of standard [NiFe] hydrogenases
      as described for Desulfovibrio gigas and Allochromatium vinosum. The data offer a
      new strategy how to engineer oxygen-tolerant hydrogenases for biotechnological
      application.

PMID- 15849359
TI  - Phosphorylation of Ser24 in the pleckstrin homology domain of insulin receptor
      substrate-1 by Mouse Pelle-like kinase/interleukin-1 receptor-associated kinase:
      cross-talk between inflammatory signaling and insulin signaling that may
      contribute to insulin resistance.
AB  - Inflammation contributes to insulin resistance in diabetes and obesity. Mouse
      Pelle-like kinase (mPLK, homolog of human IL-1 receptor-associated kinase (IRAK))
      participates in inflammatory signaling. We evaluated IRS-1 as a novel substrate
      for mPLK that may contribute to linking inflammation with insulin resistance.
      Wild-type mPLK, but not a kinase-inactive mutant (mPLK-KD), directly
      phosphorylated full-length IRS-1 in vitro. This in vitro phosphorylation was
      increased when mPLK was immunoprecipitated from tumor necrosis factor (TNF)-alpha
      treated cells. In NIH-3T3(IR) cells, wild-type mPLK (but not mPLK-KD) co
      immunoprecipitated with IRS-1. This association was increased by treatment of
      cells with TNF-alpha. Using mass spectrometry, we identified Ser(24) in the
      pleckstrin homology (PH) domain of IRS-1 as a specific phosphorylation site for
      mPLK. IRS-1 mutants S24D or S24E (mimicking phosphorylation at Ser(24)) had
      impaired ability to associate with insulin receptors resulting in diminished
      tyrosine phosphorylation of IRS-1 and impaired ability of IRS-1 to bind and
      activate PI-3 kinase in response to insulin. IRS-1-S24D also had an impaired
      ability to mediate insulin-stimulated translocation of GLUT4 in rat adipose
      cells. Importantly, endogenous mPLK/IRAK was activated in response to TNF-alpha
      or interleukin 1 treatment of primary adipose cells. In addition, using a phospho
      specific antibody against IRS-1 phosphorylated at Ser(24), we found that
      interleukin-1 or TNF-alpha treatment of Fao cells stimulated increased
      phosphorylation of endogenous IRS-1 at Ser(24). We conclude that IRS-1 is a novel
      physiological substrate for mPLK. TNF-alpha-regulated phosphorylation at Ser(24)
      in the pleckstrin homology domain of IRS-1 by mPLK/IRAK represents an additional
      mechanism for cross-talk between inflammatory signaling and insulin signaling
      that may contribute to metabolic insulin resistance.

PMID- 15849360
TI  - Wnt signaling inhibits adipogenesis through beta-catenin-dependent and 
      independent mechanisms.
AB  - Wnt signaling has been reported to block apoptosis and regulate differentiation
      of mesenchymal progenitors through inhibition of glycogen synthase kinase 3 and
      stabilization of beta-catenin. The effects of Wnt in preadipocytes may be
      mediated through Frizzled (Fz) 1 and/or Fz2 as these Wnt receptors are expressed
      in preadipocytes and their expression declines upon induction of differentiation.
      We ectopically expressed constitutively active chimeras between Wnt8 and Fz1 or
      Fz2 in preadipocytes and mesenchymal precursor cells. Our results indicated that
      activated Fz1 increases stability of beta-catenin, inhibits apoptosis, induces
      osteoblastogenesis, and inhibits adipogenesis. Although activated Fz2 does not
      influence apoptosis or osteoblastogenesis, it inhibits adipogenesis through a
      mechanism independent of beta-catenin. An important mediator of the beta-catenin
      independent pathway appears to be calcineurin because inhibitors of this
      serine/threonine phosphatase partially rescue the block to adipogenesis caused by
      Wnt3a or activated Fz2. These data supported a model in which Wnt signaling
      inhibits adipogenesis through both beta-catenin-dependent and beta-catenin
      independent mechanisms.

PMID- 15849361
TI  - Direct DNA binding activity of the Fanconi anemia D2 protein.
AB  - It is known that the Fanconi anemia D2 protein is vital for protecting the genome
      from DNA damage, but what activities this protein has are unknown. In these
      experiments we purified full-length Fanconi anemia protein D2 (FANCD2), and we
      found that FANCD2 bound to DNA with specificity for certain structures: double
      strand DNA ends and Holliday junctions. Proteins containing patient-derived
      mutations or artificial variants of the FANCD2 protein were similarly expressed
      and purified, and each variant bound to the Holliday junction DNA with similar
      affinity as did the wild-type protein. There was no single discrete domain of
      FANCD2 protein that bound to DNA, but rather the full-length protein was required
      for structure-specific DNA binding. This finding of DNA binding is the first
      biochemical activity identified for this key protein in the Fanconi anemia
      pathway.

PMID- 15849362
TI  - Fluoride induces endoplasmic reticulum stress in ameloblasts responsible for
      dental enamel formation.
AB  - The mechanism of how fluoride causes fluorosis remains unknown. Exposure to
      fluoride can inhibit protein synthesis, and this may also occur by agents that
      cause endoplasmic reticulum (ER) stress. When translated proteins fail to fold
      properly or become misfolded, ER stress response genes are induced that together
      comprise the unfolded protein response. Because ameloblasts are responsible for
      dental enamel formation, we used an ameloblast-derived cell line (LS8) to
      characterize specific responses to fluoride treatment. LS8 cells were growth
      inhibited by as little as 1.9-3.8 ppm fluoride, whereas higher doses induced ER
      stress and caspase-mediated DNA fragmentation. Growth arrest and DNA damage
      inducible proteins (GADD153/CHOP, GADD45alpha), binding protein (BiP/glucose
      responsive protein 78 (GRP78), the non-secreted form of carbonic anhydrase VI (CA
      VI), and active X-box-binding protein-1 (Xbp-1) were all induced significantly
      after exposure to 38 ppm fluoride. Unexpectedly, DNA fragmentation increased when
      GADD153 expression was inhibited by short interfering RNA treatment but remained
      unaffected by transient GADD153 overexpression. Analysis of control and GADD153(
      /-) embryonic fibroblasts demonstrated that caspase-3 mediated the increased DNA
      fragmentation observed in the GADD153 null cells. We also demonstrate that mouse
      incisor ameloblasts are sensitive to the toxic effects of high dose fluoride in
      drinking water. Activated Ire1 initiates an ER stress response pathway, and mouse
      ameloblasts were shown to express activated Ire1. Ire1 levels appeared induced by
      fluoride treatment, indicating that ER stress may play a role in dental
      fluorosis. Low dose fluoride, such as that present in fluoridated drinking water,
      did not induce ER stress.

PMID- 15849363
TI  - Evolution of matrix and bone gamma-carboxyglutamic acid proteins in vertebrates.
AB  - The evolution of calcified tissues is a defining feature in vertebrate evolution.
      Investigating the evolution of proteins involved in tissue calcification should
      help elucidate how calcified tissues have evolved. The purpose of this study was
      to collect and compare sequences of matrix and bone gamma-carboxyglutamic acid
      proteins (MGP and BGP, respectively) to identify common features and determine
      the evolutionary relationship between MGP and BGP. Thirteen cDNAs and genes were
      cloned using standard methods or reconstructed through the use of comparative
      genomics and data mining. These sequences were compared with available annotated
      sequences (a total of 48 complete or nearly complete sequences, 28 BGPs and 20
      MGPs) have been identified across 32 different species (representing most classes
      of vertebrates), and evolutionarily conserved features in both MGP and BGP were
      analyzed using bioinformatic tools and the Tree-Puzzle software. We propose that:
      1) MGP and BGP genes originated from two genome duplications that occurred around
      500 and 400 million years ago before jawless and jawed fish evolved,
      respectively; 2) MGP appeared first concomitantly with the emergence of
      cartilaginous structures, and BGP appeared thereafter along with bony structures;
      and 3) BGP derives from MGP. We also propose a highly specific pattern definition
      for the Gla domain of BGP and MGP.

PMID- 15849364
TI  - Activation of HIF-prolyl hydroxylases by R59949, an inhibitor of the
      diacylglycerol kinase.
AB  - Hypoxia-inducible factors (HIF) are heterodimeric (alpha/beta) transcription
      factors that play a fundamental role in cellular adaptation to low oxygen
      tension. In the presence of oxygen, the HIF-alpha subunit becomes hydroxylated at
      specific prolyl residues by prolyl hydroxylases. This post-translational
      modification is recognized by the von Hippel-Lindau (VHL) protein, which targets
      HIF-alpha for degradation. In the absence of oxygen, HIF-alpha hydroxylation is
      compromised and this subunit is stabilized. We have previously shown that the
      hypoxia-induced accumulation of HIF-alpha protein is strongly impaired by the
      inhibitor of diacylglycerol kinase, R59949. Here, we have investigated the
      mechanisms through which this inhibitor exerts its effect. We found that R59949
      inhibits the accumulation of HIF-1/2alpha protein without affecting the
      expression of their mRNAs. We also determined that R59949 could only block the
      accumulation of HIF-alpha in the presence of VHL protein. In agreement with this,
      the binding of VHL to endogenous HIF-alpha was significantly enhanced after
      R59949 treatment, even under hypoxic conditions. In addition, we found that
      R59949 could stimulate prolyl hydroxylase both at 21% O2 as well as at 1% O2.
      Taken together, these results reveal that R59949 is an activator of HIF prolyl
      hydroxylases. This is of particular interest when we consider that, to date,
      mainly inhibitors of these enzymes have been described.

PMID- 15849367
TI  - Developments in basic science research.
AB  - Basic science research constitutes a steadily increasing part of the Conference
      on Retroviruses and Opportunistic Infections, and the 12th conference arguably
      had the strongest showing of basic science research. Presentations on cellular
      defense factors dominated the basic science category, and some of the
      presentations provided a few surprises with regard to the mechanism by which the
      cellular defense factor APOBEC counteracts HIV-1 infection. A second cellular
      defense factor has been identified in the past year and a number of presentations
      focused on its mode of action. Similarly, evidence for new cellular factors that
      positively promote viral replication were presented. Novel findings relating to
      viral pathogenesis were featured at the meeting and some clarity was brought to
      the issue of the underlying role of viral pathogenicity and immune activation in
      lymphocyte depletion. The crystal structure of an unliganded SIV envelope was
      presented and has broad significance in terms of understanding viral infection
      and generating better immunogens for vaccines.

PMID- 15849365
TI  - Cooperation of the metalloprotease, disintegrin, and cysteine-rich domains of
      ADAM12 during inhibition of myogenic differentiation.
AB  - The extracellular domain of the mature form of ADAM12 consists of the
      metalloprotease, disintegrin, cysteine-rich, and epidermal growth factor (EGF)
      like domains. The disintegrin, cysteine-rich, and EGF-like fragments have been
      shown previously to support cell adhesion via activated integrins or
      proteoglycans. In this study, we report that the entire extracellular domain of
      mouse ADAM12 produced in Drosophila S2 cells supported efficient adhesion and
      spreading of C2C12 myoblasts even in the absence of exogenous integrin
      activators. This adhesion was not mediated by beta1 integrins or proteoglycans,
      was myoblast-specific, and required the presence of both the metalloprotease and
      disintegrin/cysteine-rich domains of ADAM12. Analysis of the recombinant proteins
      by far-UV circular dichroism suggested that the secondary structures of the
      autonomously expressed metalloprotease domain and the disintegrin/cysteine
      rich/EGF-like domains differ from the structures present in the intact
      extracellular domain. Furthermore, the intact extracellular domain (but not the
      metalloprotease domain or the disintegrin/cysteine-rich/EGF-like fragment alone)
      decreased the expression of the cell cycle inhibitor p21 and myogenin, two
      markers of differentiation, and inhibited C2C12 myoblast fusion. Thus, the novel
      protein-protein interaction reported here involving the extracellular domain of
      ADAM12 may have important biological consequences during myoblast
      differentiation.

PMID- 15849368
TI  - HIV pathogenesis and vaccine development.
AB  - New information on the crystal structures of the HIV and the simian
      immunodeficiency virus (SIV) envelopes represented one of the scientific
      highlights of the 12th Annual Conference on Retroviruses and Opportunistic
      Infections. Numerous presentations also underscored the increasing recognition of
      the central role of gut-associated lymphoid tissue in AIDS pathogenesis and
      helped reveal a better understanding of the multiple mechanisms underlying CD4+ T
      lymphocyte depletion in AIDS. Progress on vaccine development was largely
      incremental but was strongly influenced by the impact of an expanding array of
      flow cytometric assays that have revealed significant functional and phenotypic
      differences in virus-specific CD8+ cells. The interplay between host cellular and
      humoral immune responses and virus evolution was another prominent theme, and it
      underscored the challenge facing host immune responses and vaccine developers in
      attempting to thwart an ever-mutating virus.

PMID- 15849369
TI  - Complications of HIV disease and antiretroviral therapy.
AB  - Metabolic, opportunistic, and other infectious complications of HIV infection and
      antiretroviral therapy continue to be major areas of active investigation. This
      year's Conference on Retroviruses and Opportunistic Infections included many
      important presentations on the clinical aspects of HIV complications. In each
      successive year, the studies reported in the area of complications have matured
      and now include more randomized trials evaluating interventions for the
      management of HIV complications and more well-designed observational studies with
      long-term follow-up. This article will review new data presented on metabolic
      complications, including cardiovascular risk, lipid disorders and lipoatrophy,
      renal complications, hepatic complications (hepatitis B and C virus infections),
      tuberculosis, and other bacterial infections.

PMID- 15849370
TI  - Advances in antiretroviral therapy.
AB  - Antiretroviral therapy was a dominant theme of the 12th Conference on
      Retroviruses and Opportunistic Infections. Key focus areas were new drug
      advances, management strategies for treatment-naive and treatment-experienced
      patients, the growing experience with antiretrovirals in the developing world,
      prevention of mother-to-child transmission of HIV, and the implications of HIV
      resistance. This review will highlight the major findings relevant to clinicians
      and clinical investigators.

PMID- 15849371
TI  - Update of the Drug Resistance Mutations in HIV-1: 2005.
AB  - Since 2000, the International AIDS Society-USA (IAS-USA) Drug Resistance
      Mutations Group has worked as an independent entity and forged a collaborative
      process to identify key HIV-1 drug resistance mutations. The goal of the group is
      to quickly deliver accurate and unbiased information to clinical practitioners on
      HIV-1 resistance. This April 2005 version of the IAS-USA Drug Resistance
      Mutations Figures replaces the version published in this journal in October 2004.
      The IAS-USA Drug Resistance Mutations Figures are designed for use in identifying
      mutations associated with viral resistance to antiretroviral drugs and in making
      therapeutic decisions. Care should be taken when using this list of mutations for
      surveillance or epidemilogic studies of transmission of drug-resistant virus. A
      number of amino acid substitutions, particularly minor mutations, represent
      polymorphisms that, in isolation, may not reflect prior drug selective pressure
      or reduced drug susceptibility.

PMID- 15849372
TI  - Genetic factors underlying differential blood platelet sensitivity to inhibitors.
AB  - Blood platelets are not only the primary defence mechanism involved in
      physiological hemostasis, but also their disorders constitute a crucial risk
      factor in arterial thrombosis. As arterial thrombi are composed of predominantly
      platelets formed under conditions of elevated shear stress at sites of
      atherosclerotic vascular injury and disturbed blood flow, the prevention of
      arterial thrombosis has been for years the main target for antiplatelet therapy.
      Individual differences in the rate of platelet activation and reactivity markedly
      influence normal hemostasis and the pathological outcome of thrombosis. Such an
      individual variability is largely determined by environmental and genetic
      factors. These are known to either hamper platelets' response to agonists, and
      thereby mimic the pharmacological modulation of platelet function or mask therapy
      effect and sensitize platelets. Some clinical studies have indicated that
      platelet glycoprotein polymorphisms are genetic factors contributing to arterial
      thrombosis. In spite of some discrepancies between different studies, there is
      substantial evidence that the integrin beta3 P1(A2) allele, the variants
      GPIbalpha Met145 and GPIbalpha (-5C) haplotype or the integrin alpha2 haplotype 1
      (807T) each contribute to the risk for and morbidity of thrombotic disease. In
      this article, we reviewed a role of the aforementioned polymorphisms in
      modulating platelet function and platelet response to inhibitors. The paper
      focuses on the association between Pl(A1/A2) polymorphism and sensitivity (or
      resistance) to aspirin and the inhibitory efficacy of GPIIb-IIIa antagonists.
      Additionally, a potential role of 807C/T polymorphism (GPIa), polymorphisms of
      GPIb and platelet purinoreceptor P2Y12 in affecting platelet sensitivity to
      blocking agents is discussed.

PMID- 15849373
TI  - L-arginine and cardiovascular system.
AB  - L-arginine is a basic endogenous amino acid. Its significant metabolic role as
      the product of ammonia detoxification, the urea cycle metabolite, the precursor
      of proteins, ornithine, urea and creatinine, and the amino acid involved in the
      formation of active enzyme centers was very well established. The current
      interest in this amino acid refers mainly to its close relation with an important
      signal molecule nitric oxide (NO). Literature review demonstrates that L
      arginine, the only substrate of the NO production, affects cardiovascular system
      (blood vessels and heart). The majority of experimental and clinical studies
      clearly show a beneficial effect of L-arginine on endothelium in conditions
      associated with its hypofunction and thus with reduced NO synthesis. Some
      clinical studies involving healthy volunteers or patients suffering from
      hypertension and diabetes indicate that it may also regulate vascular hemostasis.
      Moreover, experiments performed on animals and in vitro data also suggest that L
      arginine may have a complex antiaggregatory, anticoagulatory and profibrinolytic
      effect. Therefore, a novel therapeutic potential of L-arginine should be taken
      into consideration.

PMID- 15849374
TI  - Drug-induced myopathies. An overview of the possible mechanisms.
AB  - Myopathy is usually a non-fatal muscle disease involving skeletal muscle
      weakness, tenderness and pain with the possibility of the plasma creatinine
      kinase elevation. There are many different types of myopathies, some of which are
      genetic, inflammatory, or related to endocrine dysfunction. Also, numerous drugs
      have been reported to possess myotoxic effect. Myopathy is included among the
      potential side-effects and toxicities associated with the lipid lowering agents,
      particularly 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitors. However, the precise mechanism of statin-induced muscle toxicity
      remains unclear. The muscle-related side-effects reported with lipid-lowering
      drugs are significant but quite rare (0.1%), when used in monotherapy; while the
      incidence of steroid-induced myopathy has varied from 7 to 60%% and chronic
      alcoholic myopathy seems to be common complication of alcoholism affecting
      approximately 50% of patients, respectively. This review focuses on the
      differential pathophysiological grounds of these muscular injuries induced by
      statins, fibrates, as well as some other agents: corticosteroids or alcohol. A
      wide spectrum of possible mechanisms and hypotheses including muscle enzyme
      defects, changes in mitochondrial function and intracellular metabolism, the
      influence on the cell membrane stability and drug interactions involving P
      glycoprotein or cytochrome P 450 system have been presented.

PMID- 15849375
TI  - Role of serotonin (5-HT)2 receptors in cocaine self-administration and seeking
      behavior in rats.
AB  - Previous studies have indicated a role of serotonin (5-HT)2 receptors in
      modulation of the behavioral effects of cocaine. In the present study, the
      efficacy of SR 46349B (a 5-HT(2A) receptor antagonist) or SDZ SER-082 (a 5-HT(2C)
      receptor antagonist) in altering cocaine seeking behavior was examined in rats.
      Rats were trained to press a lever for cocaine (0.5 mg/kg/infusion, iv) paired
      with the cue (light + tone). After stabilization of self-administration response,
      the animals underwent daily extinction sessions during which responding had no
      consequences. The cocaine seeking behavior was reinstated by cocaine priming (10
      mg/kg, ip) or by presentation of the cue. Neither SR 46349B (0.25-1 mg/kg) nor
      SDZ SER-082 (0.25-1 mg/kg) altered the maintenance of cocaine self
      administration. SR 46349B (0.5-1 mg/kg) decreased responding to the cocaine
      priming dose and reduced cue-induced reinstatement, while SDZ SER-082 failed to
      alter both cue- and cocaine priming-induced reinstatement. These findings
      indicate that 5-HT(2A) and 5-HT(2C) receptors are not significant to cocaine
      rewarding effects. However, they show the importance of the 5-HT(2A) receptors
      (but not 5-HT(2C) receptors) in cocaine-priming- and cue-provoked reinstatement.
      Since drugs that reduce cocaine seeking also alleviate cocaine craving, 5-HT(2A)
      receptor antagonists may be considered to be of possible clinical application for
      the treatment of cocaine dependence.

PMID- 15849376
TI  - Effect of NMDA receptor antagonists on behavioral impairment induced by chronic
      treatment with dexamethasone.
AB  - Severe and prolonged stress but also long-term treatment with glucocorticoids
      (GCs) have been described to cause brain damage (especially hippocampal and
      striatal neurons) in humans as well as in animals. GCs potentiate stress or
      ischemia-induced accumulation of excitatory amino acids (EAA) in the
      extracellular space of the hippocampus. It was shown that EAA play a major role
      in various neurologic disorders with cognitive dysfunction. Many authors
      suggested the neuroprotective effect of N-methyl-D-aspartate (NMDA) glutamate
      receptor antagonists in some acute or chronic neurodegenerative diseases. On the
      other hand, many NMDAreceptor antagonists produce highly undesirable side-effects
      at the doses within their putative therapeutic range. The aim of the present
      study was to evaluate the behavioral effects (memory performance, motor
      coordination, lethality and body weight) of MK-801 or memantine (MEMAN, non
      competitive NMDAreceptor antagonists) (at the doses of 25 and 50 microg/kg/day or
      2.5 and 5.0 mg/kg/day, respectively) on neurotoxicity induced by dexamethasone
      (DEX) administered chronically at the doses of 40 or 80 mg/kg/day in mice. It was
      shown that prolonged treatment (for 10 days) with DEX at the dose of 80 mg/kg/day
      (but not at 40 mg/kg/day) significantly decreased the retention time in the
      memory task in mice and impaired the motor coordination in "chimney" test.
      Neither MK-801 nor MEMAN (at the both doses used) were able to counteract the
      behavioral impairment induced by DEX administration. Moreover, the potentiation
      of the body weight reduction and lethality induced by DEX were noted in mice co
      treated with MK-801 or MEMAN. The above findings suggest that MK-801 or MEMAN at
      the doses used have no neuroprotective effect. On the contrary, both NMDA
      receptor antagonists potentiate the toxicity of DEX given chronically.

PMID- 15849377
TI  - Participation of adenosine system in the ketamine-induced motor activity in mice.
AB  - The influence of adenosine receptor ligands on ketamine-induced locomotor
      activity was studied in mice. Ketamine-induced hyperactivity (10 mg/kg) was
      significantly and dose-dependently attenuated by CGS 21680 (selective A(2A)
      receptor agonist), and NECA (A1/A2 adenosine receptor agonist), but not by CPA
      (cyclopentyladenosine, selective A1 adenosine receptor agonist). Motor activity
      produced by subthreshold dose (2.5 mg/kg) of ketamine was significantly increased
      by DMPX (selective A1 receptor antagonist) and caffeine (A1/A2 adenosine receptor
      antagonist), but not by DPCPX (selective A1 adenosine receptor antagonist). These
      results suggest that adenosinergic system is involved in ketamine-induced motor
      activity and seem to indicate a predominant role of A(2A) adenosine receptor in
      this effect.

PMID- 15849378
TI  - Effect of the combined administration of ethanol and acamprosate on rabbit EEG.
AB  - Central effect of ethyl alcohol and acamprosate is based on similar mechanisms.
      It is mainly connected with their effect on GABAergic, glutamatergic,
      serotonergic and opioid transmission. Thus, the question arises whether
      acamprosate administered together with alcohol increases acute central effects of
      ethanol. We have studied the effect of joint administration of acamprosate with
      ethanol in rabbits on EEG results from: frontal cortex, hippocampus and midbrain
      reticular formation. Acamprosate was applied into the stomach at a single dose of
      400 mg kg(-1) or repeated doses of 200 mg kg(-1)/day (for 14 days). Ethanol at
      the dose of 0.8 g kg(-1) was administered iv 120 min after a single dose of
      acamprosate, or 4 h after the last dose of the drug. Ethanol caused an increase
      in the slow frequencies (0.5-4 Hz) in the recording, as well as a marked decrease
      in the fastest frequencies (13-30 and 30-45 Hz). Acamprosate administered jointly
      with ethanol increased the effect of ethanol on EEG recording; the amount of the
      fastest frequencies was decreased. When administered as repeated doses, it
      enhanced alcohol-related changes in EEG, both within slow and fast frequencies.
      Consumption of ethanol during acamprosate treatment may lead to intensification
      of central effects of ethanol.

PMID- 15849379
TI  - Protective effect of catechin on ischemia-reperfusion-induced renal injury in
      rats.
AB  - There is increasing evidence to suggest that toxic oxygen radicals play a role in
      the pathogenesis of ischemia/reperfusion (I/R) injury in the kidney. This study
      was designed to investigate the effects of catechin, a bioflavonoid, in I/R
      induced renal failure in rats. The protective effect of catechin against the
      damage inflicted by reactive oxygen species (ROS) during renal I/R was
      investigated in Sprague Dawley rats using histopathological and biochemical
      parameters. In one set of experiments, animals were unilaterally nephrectomized,
      and subjected to 45 min of left renal pedicle occlusion, and in another set both
      the renal pedicles were occluded for 45 min followed by 24 h of reperfusion.
      Catechin (40 mg/kg, po) was administered twice daily for 4 days and 2 h prior to
      ischemia. At the end of the reperfusion period, rats were sacrificed.
      Thiobarbituric acid reactive substances (TBARS), reduced glutathione levels,
      glutathione reductase, catalase, and superoxide dismutase activities were
      determined in renal tissue. Serum creatinine and blood urea nitrogen
      concentrations were measured for the evaluation of renal function. Ischemic
      control animals demonstrated severe deterioration of renal function, renal
      morphology and a significant renal oxidative stress. Pretreatment of animals with
      catechin markedly attenuated renal dysfunction, morphological alterations,
      reduced elevated TBARS levels and restored the depleted renal antioxidant
      enzymes. The findings imply that ROS play a causal role in I/R-induced renal
      injury, and catechin exerts renoprotective effects probably by the radical
      scavenging and antioxidant activities.

PMID- 15849380
TI  - Synthesis of 6-O-acyl-L-ascorbic acid-2-O-phosphates and study of their
      antioxidant effects in 95-D cells.
AB  - Reactive oxygen species (ROS) are believed to play a role in development of
      several diseases. L-ascorbic acid (AsA) is a kind of excellent antioxidant, but
      its instability in solution and hydrophilicity limits the wide use of it.
      Structural modifications of AsAby the introduction of lipophilic moieties can
      lead to derivatives with increased stability against thermal and oxidative
      degradation. In this study, a series of 6-O-acyl-L-ascorbic acid-2-O-phosphates
      (6-Acyl-AA-2Ps) were synthesized from a stable AsA derivative, L-ascorbic acid-2
      phosphate ester magnesium (AA-2P) and long-chain fatty acids, act as radical
      scavengers for ROS and free radicals. ROS scavenging ability was investigated by
      CDCFH method in 95-D cells. The effect of 6-Acyl-AA-2P series on viability of 95
      D cells was also studied by MTT method. All the synthesized compounds show
      stronger ROS scavenging ability and cytotoxicity than those of AsA. High
      performance liquid chromatography assay demonstrates that 6-Acyl-AA-2Ps are
      stable in RPMI-1640 medium and can easily permeate cell membrane and be converted
      into AsA and L-ascorbic acid-2-phosphate ester. The results also show that the
      activity of 6-Acyl-AA-2Ps increases with a decrease in the length of the alkyl
      chain but cytotoxicity decreases. The optimum length of alkyl side chain is 12
      carbons. In summary, 6-Laur-AA-2P should be one of the best candidates for the
      development of an efficient new AsA derivative and should be further investigated
      in detail.

PMID- 15849381
TI  - Effect of rutin on total antioxidant status of rats exposed to cigarette smoke.
AB  - Exposure to tobacco smoke impairs the antioxidant defense mechanisms. In female
      Wistar rats fed on regular rodent chow and supplemented with a flavonoids rutin,
      Trolox Equivalent Antioxidant Capacity (TEAC) was measured as an ABTS-radical
      cation reduction power in plasma, lungs, liver, brain and kidneys. Exposure to
      smoke reduced the TEAC values in the liver, brain and kidneys and enhanced
      antioxidant potential in lungs in comparison to control animals. In plasma no
      change of TEAC value was observed. Supplementation with rutin increased
      antioxidant status of plasma, but TEAC was reduced in kidneys, brain and liver of
      smoke-exposed animals when compared to the matched controls. In lung no change in
      TEAC was found. The results suggest a complex pattern of influence of tobacco
      smoke on blood and tissue antioxidant mechanisms. The enrichment of diet with non
      nutrient antioxidant rutin did not result in direct improvement of tissue TEAC
      with the exception of blood plasma.

PMID- 15849382
TI  - Antioxidant effect of Aloe vera gel extract in streptozotocin-induced diabetes in
      rats.
AB  - In the present study, an attempt has been made to evaluate the presence of
      antioxidant property in the alcoholic extract of Aloe vera leaf gel. Oral
      administration of Aloe vera gel extract at a concentration of 300 mg/kg to
      diabetic rats significantly decreased the levels of blood glucose, glycosylated
      hemoglobin and increased hemoglobin. The increased levels of lipid peroxidation
      and hydroperoxides in tissues of diabetic rats were reverted back to near normal
      levels after the treatment with gel extract. The extract treatment also resulted
      in a significant increase in reduced glutathione, superoxide dismutase, catalase,
      glutathione peroxidase and glutathione-S-transferase in the liver and kidney of
      diabetic rats. These results clearly show the antioxidant property of Aloe vera
      gel extract. The extract was also more effective than glibenclamide in restoring
      the values of these parameters.

PMID- 15849383
TI  - Inhibitory effect of albendazole and its metabolites on cytochromes P450
      activities in rat and mouflon in vitro.
AB  - Cytochromes P450 (CYP) belong to the most important biotransformation enzymes,
      therefore, their inhibition may lead to serious pharmacological and toxicological
      consequences. Albendazole (ABZ) is a benzimidazole anthelmintic widely used in
      human and veterinary medicine. The effects of ABZ on CYP were investigated on the
      rat (Rattus norvergicus) and mouflon (Ovis musimon) hepatic microsomes. Besides
      ABZ, its two main metabolites (albendazole sulfoxide, ABZSO, and albendazole
      sulfone, ABZSOO) were tested to clarify which compound is responsible for the
      inhibitory effect. After preincubation of microsomes with the benzimidazoles (1,
      5 and 25 microM), CYP activities, ethoxyresorufin O-deethylase (EROD) and
      benzyloxyresorufin O-dearylase activities were measured. The results showed that
      both ABZ and ABZSO, but not ABZSOO, exhibited significant potency to inhibit CYP
      activities measured in both tested species. Since ABZ as well as ABZSO are known
      inducers of EROD activity, our results clearly demonstrate that the drug can act
      as inducer and also as inhibitor of the same enzyme. In in vitro studies the CYP
      inhibition may mask the CYP induction. The extent of inhibition observed in
      mouflon was significantly higher than in rat. This finding emphasizes the
      importance of performance of inhibition studies in target animal species.
      Possible consequences of CYP inhibition should be taken into account during the
      anthelmintic therapy of mouflons with ABZ.

PMID- 15849384
TI  - Effect of kaempferol on the production and gene expression of monocyte
      chemoattractant protein-1 in J774.2 macrophages.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is produced by activated macrophages,
      and is involved in pathogenesis of cardiovascular and neurodegenerative
      disorders. There is a need to develop drugs that inhibit excessive infiltration
      of monocytes and lymphocytes to the arterial wall and central nervous system. The
      aim of this study was to evaluate the effect of kaempferol on the (MCP-1) gene
      expression and MCP-1 protein release by J774.2 macrophage cultures in vitro.
      Kaempferol given both before and after lipopolysaccharide (LPS) administration
      reduced secretion of MCP-1. Kaempferol administered before LPS stimulation
      significantly decreased the number of copies of MCP-1 mRNA. The results suggest
      that kaempferol inhibits MCP-1 production at the transcriptional level, and that
      this is an additional anti-inflammatory mechanism of action of this flavonoid.

PMID- 15849385
TI  - Nitric oxide effect on 5-hydroxytryptamine-induced vasoconstrictions of isolated
      smooth muscle.
AB  - The aim of the present study was to investigate a nitric oxide (NO) involvement
      in the mediation of a 5-HT-induced vasoconstriction response in the rat portal
      vein in vitro. Isolated rat portal vein segments were placed in organ baths for
      isometric force measurement. 5-HT (3 x 10(-8) M-3 x 10(-4) contracted portal vein
      preparations (EC50 = 7 x 10(-7) M) in a concentration-dependent manner. The
      vasoconstriction induced by 5-HT was significantly increased in endothelium
      denuded vessels. Pretreatment with Nomega-nitro-L-arginine methyl ester (L-NAME
      100 microM) enhanced the contractive response to 5-HT either in intact or
      endothelium-denuded vessels. However, ketanserin (0.1 microM) abolished 5-HT
      induced vasoconstrictions (EC50 = 4.6 x 10(-8) M). Furthermore, a non-selective 5
      HT(1B/D) receptor agonist, sumatriptan (1 x 10(-10) M-1 x 10(-5) M), induced a
      reduction of spontaneous rhythmic contractions also in endothelium-intact
      vessels. However, 5-HT- induced vasoconstriction was unaffected by propranolol
      (10 microM). The data support the hypothesis of the existence of serotonergic
      innervations modulating the contractility of vascular smooth muscle. These
      findings are consistent with the hypothesis that the vasoconstrictor activity of
      5-HT in smooth muscle was mediated by activation of 5-HT(1B/D) and 5-HT(2B)
      receptor subtypes involving the endothelium-dependent mechanism.

PMID- 15849386
TI  - Trans-4-aminocrotonic acid (TACA), a potent agonist of GABA(A) and GABA(C)
      receptors, shows a proconvulsant action in the electroconvulsive threshold test
      in mice.
AB  - In the present study, we evaluated TACA (a potent agonist of GABA(A) and GABA(C)
      receptors) in the electroconvulsive threshold test in mice. Surprisingly, TACA
      (at 15 and 25 mg/kg) significantly decreased the threshold. The highest
      ineffective dose of TACA was estimated as 10 mg/kg. The obtained results indicate
      that the drug enhancing GABAergic transmission may possess proconvulsant
      properties in the electroconvulsive test. Such effect was completely opposite to
      our primary assumption and expectance.

PMID- 15849387
TI  - Prophylactic effect of lithium in bipolar affective illness may be related to
      serotonin transporter genotype.
AB  - Serotonin transporter promoter length polymorphism (5-HTTLPR) has been implicated
      in the pathogenesis of mood disorders and in the therapeutic response to
      serotonergic drugs. In this study, the 5-HTTLPR was estimated in 67 patients with
      bipolar mood disorder, receiving lithium carbonate for prophylactic purposes for
      the period of more than 5 years (mean 15 years). The patients were divided into
      excellent responders (n = 18), partial responders (n = 35) and poor responders (n
      = 14). In lithium non-responders, the genotype s/s and the allele s was
      significantly more frequent than in excellent and partial responders. The
      obtained results are discussed in view of other studies showing an association of
      S genotype with worse response to serotonergic drugs. A supposition is made that
      prophylactic management of bipolar illness can be optimized by defining 5-HTTLPR
      genotype.

PMID- 15849388
TI  - Effects of thiopental and propofol on heart rate variability during fentanyl
      based induction of general anesthesia.
AB  - Anesthetics depress the autonomic nervous system. The effects of thiopental and
      propofol on heart rate variability (HRV) during fentanyl-based induction of
      general anesthesia were studied in one hundred patients. We observed different
      effects of fentanyl, thiopental and propofol on HRV. Fentanyl decreased total
      power of HRV and low frequency power (LF), but not high frequency power (HF),
      indicating a greater reduction of cardiac sympathetic activity. Thiopental and
      propofol caused the further reduction of HRV and decreased HF power. Thiopental
      increased LF power and LF/HF ratio, indicating that the vagolytic effect is
      associated with the increase in sympathetic activity. Propofol preserved the LF
      power, indicating that the cardiac parasympathetic activity is reduced more than
      the sympathetic activity.

PMID- 15849389
TI  - Antithrombotic effect of captopril and enalapril in old rats.
AB  - In the present study, we have shown considerably accelerated thrombosis in old
      rats in comparison with adult rats, which may be related to the impaired
      hemostatic balance in these animals. In old rats, captopril and enalapril caused
      a marked reduction of venous thrombus weight. The mechanism of antithrombotic
      action of these drugs seems to be dependent on the suppression of coagulation
      cascade and the enhancement of the fibrinolytic processes.

PMID- 15849390
TI  - [Rickets prophylaxis under current recommendations].
AB  - AIM OF THE STUDY: We analysed the compliance of current recommendations
      concerning rickets prevention in Poland. MATERIAL AND METHODS: The study group
      consisted of 65 infants hospitalised because of emergency problems. In each case,
      the medical history included prophylaxis of rickets and feeding pattern. In most
      cases (80%) we measured calcium, phosphate, and alkaline phosphatase in the
      serum. RESULTS: Vitamin D3 was overdosed in 70% of infants. 14% of children were
      diagnosed as rachitic in outpatient department before hospitalisation, but
      neither the clinical symptoms nor the laboratory test confirmed the diagnosis.
      This confirms the observation, that rickets is diagnosed too often, usually on
      the basis of isolated craniotabes in young infants. CONCLUSION: In the context of
      changing recommendations for prophylaxis of rickets, we recommend more careful
      prescribing of vitamin D3 preparations.

PMID- 15849391
TI  - [Antioxidative properties of human milk].
AB  - Human milk, despite numerous advantages, has also antioxidative properties.
      Oxidative stress is implicated in bronchopulmonary dysplasia, retinopathy of
      prematurity and necrotizing enterocolitis. Therefore, the influence of human milk
      on oxidative stress intensity in breast-fed neonates and infants is a significant
      issue. The concentration of antioxidants in milk depends on mother's diet,
      vitamins supplementation during pregnancy and lactation and geographical area of
      domicile. Breast-fed children have higher antioxidative capacity in blood and
      lower oxidative stress intensity as compared to formula-fed children. Storage
      increases the antioxidative activity of human milk. Maternal smoking augments
      oxidative damage in children and lowers the antioxidative capacity of milk.

PMID- 15849392
TI  - [Is antenatal corticosteroid administration associated with increased acid
      gastroesophageal reflux in preterm neonates?].
AB  - THE AIM OF THE STUDY: Preliminary assessment of the incidence of acid
      gastroesophageal reflux in preterm neonates with and without antenatal
      administration of steroids. MATERIAL AND METHODS: Analysis of 96 neonates born
      before 34 weeks of pregnancy was undertaken. The patients were divided into two
      groups: I - those who received antenatal corticosteroids n=22; II - those who
      received no antenatal corticosteroids n=74. All patients had 24-hour pH-metry and
      basing on the result of this examination we diagnosed or excluded acid
      gastroesophageal reflux. RESULTS: In group I gastroesophageal reflux was
      diagnosed in 9/22 neonates (40.9%), in group II in 12/72 (16.2%), odds
      ratio=3.58. CONCLUSIONS: The frequency of acid gastroesophageal reflux is higher
      in preterm infants who received antenatal corticosteroids.

PMID- 15849393
TI  - [Gastroesophageal reflux disease presenting as severe bronchial asthma in an 18
      months old child].
AB  - It is known that gastro-esophageal reflux can trigger bronchospasm among children
      with asthma and cystic fibrosis as well as in children without chronic
      respiratory tract disorders. In our practice we have met only once with the case
      of a child misdiagnosed as having severe asthma in whom surgical treatment of
      gastro-esophageal reflux disease ended with full withdrawal of respiratory
      symptoms. On the basis of this case we conclude that the diagnostic procedures
      should be performed in cases of asthma resistant to typical treatment.

PMID- 15849394
TI  - [Long-term observation of children with previously proved Helicobacter pylori
      infection].
AB  - AIM OF THE WORK: Long-term observation of children previously infected with
      Helicobacter pylori (HP) and evaluation of the reinfection rate after successful
      therapy. 29 children were included in the study: 16 girls and 13 boys, aged 9-20
      years, who in 1998 were diagnosed as having gastritis and/or duodenitis and being
      infected with Helicobacter pylori. After the treatment, Urea Breath Test (UBT)
      was performed to evaluate eradication of HP. The test was repeated after 3 and 5
      years. In 1998, UBT was negative in 24 of 29 patients, confirming eradication of
      HP. Three years after treatment, UBT revealed the presence of HP in 7 patients
      (24.1%) - 5 of them were children in whom eradicative therapy was unsuccessful;
      in the other two the result of UBT confirmed reinfection. RESULTS: Results of UBT
      performed after next 2 years remained the same. CONCLUSIONS: HP reinfection rate
      after successful therapy is low among children and adolescents even in the
      environment where the bacteria is widely spread. Elimination of HP diminishes the
      rate of recurrence of gastric symptoms; only in some patients remission is
      complete.

PMID- 15849395
TI  - [Therapeutic difficulties in a patient with ulcerative colitis and concomitant
      HBV and HCV infection].
AB  - The aim of the paper was to describe therapeutic difficulties in a patient with
      ulcerative colitis. In the long-term clinical course of the disease a concomitant
      infection with hepatotropic viruses (HBV, HCV) was diagnosed. Due to the
      different treatment of autoimmunological diseases and chronic viral hepatitis the
      necessity of further search of therapeutic schedules for this group of patients
      is still needed.

PMID- 15849396
TI  - [Autoimmunity in children with chronic hepatitis C treated with interferon alpha
      and ribavirin].
AB  - The role of interferon alpha or the virus itself in the pathogenesis and the risk
      of autoimmunological disorders in patients infected with HCV, still remain
      unknown, especially in children. The aim of the study was to evaluate the
      incidence of autoantibodies and the risk of autoimmunological disorders in
      children with chronic hepatitis C, treated with interferon alpha and ribavirin in
      the Department of Paediatrics, Paediatric Gastroenterology and Oncology in
      Gdansk. In the studied group of 12 patients, in 4 cases autoantibodies were
      present in low titers prior to the treatment and they had no prognostic value for
      the response to the therapy or the risk of autoimmunological disorders. Positive
      response for the treatment was achieved in 4 cases; in 3 cases indications for
      discontinuation of the therapy were established. During the therapy with
      interferon alpha and ribavirin, in 2 children elevation of serum titers of
      antibodies to liver-kidney microsome type 1 (anti-LKM1) (> 1:640) with normal
      gammaglobulin levels was noted. In none of the children autoimmunological
      disorders were observed.

PMID- 15849397
TI  - [Free radical reactions and activity of antioxidant barrier in children with
      chronic hepatitis B].
AB  - Recent research has shown that highly reactive oxygen species may take part in
      pathogenesis of many diseases, in particular chronic inflammatory processes. It
      was demonstrated that the activation of the inflammatory process is linked with
      generation of significant quantities of free radicals. This may lead to
      uncontrolled free radical reactions, particularly in case of antioxidant barrier
      insufficiency. THE AIM OF THE STUDY: To assess the biochemical parameters of
      oxidative stress, activation of glutathione peroxidase (GPX) and superoxide
      dismutase (SOD1) in erythrocytes of children with chronic hepatitis B (CBH).
      MATERIALS AND METHODS: Group of 47 children aged from 7 to 18 years with
      histopathologically confirmed CBH was studied. The content of carbonyl groups in
      plasma proteins and activity of SOD1 and GPX in the erythrocytes was evaluated.
      The control group consisted of 61 healthy children aged from 7 to 18 years.
      RESULTS: Verified statistically with Mann-Whitney U test. Significantly higher
      content of plasma proteins' carbonyl groups was found in the study group (1.07 +/
      0.33 nmol/mg protein) than in the control group (0.86 +/- 0.2, p < 0,001). The
      activity of GPX [U/gHb] was lower in group of children with CBH (18.7 +/- 9.7)
      than in healthy children (26.1 +/- 0.2, p =0.005). A significantly higher
      activity or SOD1 [U/gHb] was found in children with CBH (2470+/- 714) as compared
      with healthy controls (1857+/- 782, p =0.006). CONCLUSIONS: In patients with CBH
      the intensification of free radicals' reactions can be observed, which confirms
      the role of ROS in its pathogenesis. One of the reasons for this phenomenon may
      be due to the inappropriate activity of antioxidant barrier enzymes. The
      elevation of SOD activity seems to be a response to increased oxidative stress.

PMID- 15849398
TI  - [Antibiotics in lower respiratory tract infection].
AB  - THE AIM OF THE STUDY: Comparison of clinical outcome of lower respiratory tract
      infections in small children treated or not treated with antibiotics. MATERIAL
      AND METHODS: Eighty seven children aged from 2 months to 5 years admitted to
      hospital with mild to moderate bronchitis and/or pneumonia were randomly
      allocated to one of two groups: group A children were treated with antibiotics
      and group B patients were not. The children remained under close clinical
      observation. The clinical outcome was considered good if symptoms of the disease
      decreased after 72 hours. In case of no clinical improvement or worsening, the
      children from group B received antibiotics and in children from group A
      antibiotic therapy was changed. RESULTS AND CONCLUSIONS: There were no
      significant differences between the two groups in the course of the disease, the
      frequency of pulmonary complications and recurrence during one month of follow
      up.

PMID- 15849399
TI  - [Is there a link between chronic chlamydial infection and childhood asthma?].
AB  - AIM OF THE STUDY: The paper explores the possible role of chronic chlamydial
      infection in childhood bronchial asthma. MATERIAL AND METHODS: Sera of 51
      asthmatic children and 36 controls were examined by ELISA in search for specific
      IgA anti-Chlamydia pneumoniae and anti-Chlamydia trachomatis. RESULTS: Results
      were positive for Chlamydia pneumoniae in 7/51 children with asthma compared with
      1/36 controls. Specific IgA anti-Chlamydia trachomatis antibodies were detected
      in 2/51 patients with asthma and in one of the 36 controls. Infected children,
      more often than asthmatics without specific chlamydial IgA, suffered from more
      severe forms of asthma and required multiple-drug therapy, but none of the
      differences appeared statistically significant.

PMID- 15849400
TI  - [Erythema nodosum of tuberculous etiology in a 18 months old girl].
AB  - The authors report a case of an 18-months old girl with primary tuberculosis,
      where erythema nodosum was the main symptom. She received BCG vaccination on the
      first day of life according to the Polish vaccination programme. Although there
      was no postvaccinal scar when she was 12 months old, she was not revaccinated. On
      hospitalisation, the tuberculin skin test was strongly positive. The girl had a
      confirmed contact with tuberculosis. On the base of the anamnestic data and the
      clinical course, Erythema nodosum of tuberculous etiology was diagnosed and
      treatment was introduced. Erythema nodosum is not specific for tuberculosis but
      in the differential diagnosis tuberculosis should be taken into consideration.

PMID- 15849401
TI  - [Role of parvovirus B19 as a causative agent for arthritis in children --
      preliminary studies].
AB  - INTRODUCTION: Parvovirus B19 infection can be associated with arthritis in
      children and adults. The causative role of PB19 infection in arthritis and
      ulcerative synovitis would prove the etiology of juvenile idiopathic (jia) and
      reumatoid arthritis (ra). AIM: The aim of this study was the evaluation of the
      role of PB 19 infection in children's arthritis. MATERIAL AND METHODS: The group
      of 41 children with the diagnosis of jia, arthralgia, reactive arthritis and
      nodular erythema according to EULAR criteria was examined. In early stage of
      arthritis lasting less than 3 months, there were 22 and in prolonged period
      lasting more than 3 months there were 19 children. RESULTS: No evidence of PB19
      genome was detected by PCR reaction in blood of the examined patients. The
      possible reasons of the obtained negative results in this study were discussed.
      CONCLUSIONS: PB19 research should be performed in more cases of children's
      arthritis, both using PCR and by serological methods.

PMID- 15849402
TI  - [Clinical value of neopterin. Part I].
AB  - Neopterin concentration can be used to detect the activation of the cellular
      immune system. Neopterin synthesis is the sum of all positive and negative
      regulating factors on the monocyte/macrophage populations activated by interferon
      gamma, which is mainly produced by activated T lymphocytes. Neopterin can be
      determined in serum, plasma and other body fluids such as urine, cerebrospinal
      fluid, saliva, synovial fluid, ascitic fluid. The normal range of the neopterin
      concentration in serum or plasma is below 10 nmol/l. The applications for
      neopterin as a laboratory parameter for clinical diagnosis are: infections,
      autoimmune diseases, malignant diseases, posttransplant monitoring, blood
      transfusions, immunomodulatory therapy and treatment monitoring. Our own research
      results will be presented in part II of this study.

PMID- 15849403
TI  - [Undernutrition in hospitalised children. Part I].
AB  - THE AIM OF THE STUDY: Determination of the incidence of undernutrition among
      children on admission to hospital. MATERIAL AND METHODS: In 818 patients aged l
      week to 20 years admitted to Paediatric Department from January to May 2004, the
      height and body mass was recorded and body mass index (BMI) was calculated. The
      incidence of undernutrition in this population was calculated. RESULTS: Body mass
      below 10th percentile was found in 158 children (19.3%). including 96 with body
      mass <3 percentile. Undernutrition was more frequent in children below 5 year of
      age (22.16%) than in the older ones (16.74%). CONCLUSIONS: Undernutrition among
      children admitted to hospital is relatively frequent and can make treatment more
      difficult and expensive.

PMID- 15849404
TI  - An overview of the CCAAT-box binding factor in filamentous fungi: assembly,
      nuclear translocation, and transcriptional enhancement.
AB  - Filamentous fungi are frequently used for the production of industrial enzymes,
      since they produce a variety of enzymes including polysaccharide-degrading
      enzymes. Among the many filamentous fungi, Aspergillus species, such as A. oryzae
      and A. niger, are known as strong producers of amylolytic enzymes. We have been
      studying on the regulatory mechanisms underlying the expression of A. oryzae
      amylolytic genes. Based on analyses using a hybrid model system of A. nidulans
      transformed by a gene encoding A. oryzae Taka-amylase A, the major amylase
      (taaG2), we have found that three factors, CCAAT-box binding protein, CreA, and
      AmyR, are involved in taaG2 gene expression and regulation. In this review, the
      focus is on the CCAAT-box binding protein of filamentous fungi. The assembly,
      nuclear translocation, and transcriptional enhancement mechanisms of the CCAAT
      box binding protein are discussed.

PMID- 15849405
TI  - Structure and function of bacterial super-biosystem responsible for import and
      depolymerization of macromolecules.
AB  - Generally, when microbes assimilate macromolecules, they incorporate low
      molecular-weight products derived from macromolecules through the actions of
      extracellular degrading enzymes. However, a Gram-negative bacterium, Sphingomonas
      sp. A1, has a smart biosystem for the import and depolymerization of
      macromolecules. The bacterial cells directly incorporate a macromolecule,
      alginate, into the cytoplasm through a "superchannel", as we named it. The
      superchannel consists of a pit on the cell surface, alginate-binding proteins in
      the periplasm, and an ATP-binding cassette transporter in the inner membrane.
      Cytoplasmic polysaccharide lyases depolymerize alginate into the constituent
      monosaccharides. Other than the proteins characterized so far, novel proteins
      (e.g., flagellin homologs) have been found to be crucial for the import and
      depolymerization of alginate through genomics- and proteomics-based
      identification, thus indicating that the biosystem is precisely constructed and
      regulated by diverse proteins. In this review, we focus on the structure and
      function of the bacterial biosystem together with the evolution of related
      proteins.

PMID- 15849406
TI  - Myricitrin degraded by simulated digestion inhibits oxidation of human low
      density lipoprotein.
AB  - The inhibitory effects of myricitrin on the oxidation of human low-density
      lipoprotein were investigated before and after its degradation by simulated
      digestion. Myricitrin strongly inhibited the low-density lipoprotein oxidation
      induced by either 2,2'-azobis (2-amidinopropane) dihydrochloride or CuSO4 in a
      concentration-dependent manner. Myricitrin was very stable under an acidic
      condition (pH 1.8) corresponding to the gastric environment, but it was easily
      degraded under an alkaline condition (pH 8.5) corresponding to the intestinal
      environment. However, degraded myricitrin also had a strong inhibitory effect on
      the oxidative degradation of alpha-tocopherol, cholesterol and apolipoprotein B
      100 in low-density lipoprotein. Our study revealed that myricitrin was degraded
      into many components under a mildly alkaline condition, but the degraded
      myricitrin still retained the free radical-scavenging and copper-chelating
      activities toward low-density lipoprotein.

PMID- 15849407
TI  - Enhancement of linear gramicidin expression from Bacillus brevis ATCC 8185 by
      casein peptide.
AB  - Bacillus brevis (Brevibacillus parabrevis) ATCC 8185 synthesizes two kinds of
      antibiotic peptides, cyclopeptide tyrocidine and linear gramicidin. The
      production of linear gramicidin can be induced by the standard method (using a
      skim milk medium for pre-culture and beef broth for the main culture) employed
      for the induction of tyrocidine. In this study, we tried to determine the optimal
      growth medium for B. brevis ATCC 8185 for synthesizing linear gramicidin. The
      yield of linear gramicidin produced by the standard method was 3.11 microg/ml.
      When beef broth was used both as the pre-medium and the main medium, the yield of
      the antibiotic was only 0.59 microg/ml. To confirm the influence of skim milk,
      the strain was grown in a 1% skim milk medium. As a result, the amount of linear
      gramicidin produced reached 20.3 microg/ml. These findings show the importance of
      skim milk in the production of linear gramicidin. In the skim milk medium, the
      cells produced an extracellular protease 2 h before the linear gramicidin was
      expressed. The 1% skim milk medium pretreated by this protease did not allow the
      induction of linear gramicidin into the cells, and protease activity was not
      detected in the supernatant of the culture. When the cells were cultivated in a
      1% egg albumin medium, protease activity from the supernatant of the culture was
      detected, but production of linear gramicidin was not observed. Therefore, a 1%
      casein medium was used for production of linear gramicidin. As a result, the
      yield of linear gramicidin produced in the medium reached 6.69 microg/ml. We
      concluded that a digested product of the extracellular protease from casein
      enhances linear gramicidin production.

PMID- 15849408
TI  - Prodrug-oriented molecular design of neonicotinoids: preparation of imidacloprid
      related 5,5-dimethoxy-1,3-diazacyclohexane derivatives and their insecticidal
      activity.
AB  - Prodrug-oriented molecular design was attempted for the potent acyclic
      neonicotinoid insecticide, clothianidin (1-(2-chloro-5-thiazolylmethyl)-3-methyl
      2-nitroguanidine). Molecules bearing a CH2COCH2 bridge linking the 1,3-NH ends of
      clothianidin or their acetals would possibly be hydrolyzed, regenerating the
      mother compounds. This strategy was used to prepare seven acetals of clothianidin
      based molecules that combined 2-chloro-5-thiazolylmethyl, 6-chloro-3
      pyridylmethyl or 3-tetrahydrofurfuryl with a nitroimine, cyanoimine or
      nitromethylene group. The key intermediate, 1,3-diamino-2,2-dimethoxypropane, was
      prepared from the dihydroxyacetone dimer in four steps. A selected acetal showed
      a characteristic nerve-impulse pattern for neonicotinoids on an excised American
      cockroach ganglion, although the neuroblocking activity was fairly low. Some
      acetals were highly insecticidal against the pea aphid at 0.8-20 ppm 7 days after
      a spray treatment, this being in a contrast to their far weaker activity by
      injection into American cockroaches. The biological results suggest that the
      intrinsic insecticidal activities of the acetals are weak, but would exhibit
      enhanced activity if hydrolyzed in an external environment.

PMID- 15849409
TI  - Effects of the cell wall of Kluyveromyces marxianus YIT 8292 on the plasma
      cholesterol and fecal sterol excretion in rats fed on a high-cholesterol diet.
AB  - The cellular components involved in the hypocholesterolemic activity of
      Kluyveromyces marxianus YIT 8292 were examined in rats fed on a high-cholesterol
      diet. Whole cells (KM) were heated at 115 degrees C for 10 minutes and
      fractionated into water-soluble extract 1 and the insoluble residue (KM-CW).
      After mechanical disruption by glass beads, KM-CW was separated into the cell
      wall (KM-W) and water-soluble extract 2. Plasma total cholesterol was decreased
      by feeding KM-CW or KM-W, but was not changed by feeding extract 1 or extract 2.
      Feeding KM-CW and KM-W increased the fecal sterol excretion and concentration of
      short-chain fatty acids (SCFA) in the cecum. The hypocholesterolemic activity of
      KM-CW was completely abolished by the enzymatic degradation of alpha-mannan and
      beta-glucan. These results suggest that alpha-mannan and beta-glucan were the
      major active components of KM, and that its hypocholesterolemic activity may be
      attributable to the increasing fecal sterol excretion and/or production of SCFA.

PMID- 15849410
TI  - PCR method for detecting trace amounts of buckwheat (Fagopyrum spp.) in food.
AB  - Buckwheat often causes severe allergic reactions, even when its ingestion level
      is extremely low. Therefore, buckwheat is listed in several countries as a common
      food allergen. In addition to common buckwheat and Tartarian buckwheat that are
      cultivated and consumed widely, wild buckwheat may be potentially allergenic.
      Food containing undeclared buckwheat poses a risk to patients with the buckwheat
      allergy. We describe in this report a PCR method to detect buckwheat DNA by using
      primers corresponding to the internal transcribed spacer region and the 5.8S rRNA
      gene. The method is buckwheat-specific and compatible with both cultivated and
      wild buckwheat of the Fagopyrum spp. Its sensitivity was sufficient to detect 1
      ppm (w/w) of buckwheat DNA spiked in wheat DNA. This method should benefit food
      manufacturers, clinical doctors, and allergic patients by providing information
      on the presence of buckwheat contamination in food.

PMID- 15849411
TI  - Synthesis of novel heterobranched beta-cyclodextrins having beta-D-N
      acetylglucosaminyl-maltotriose on the side chain.
AB  - From a mixture of N-acetylglucosaminyl-beta-cyclodextrin (GlcNAc-betaCD) and
      lactose, beta-D-galactosyl-GlcNAc-betaCD (Gal-GlcNAc-betaCD) was synthesized by
      the transfer action of beta-galactosidase. GlcNAc-maltotriose (Glc3) and Gal
      GlcNAc-Glc3 were produced with hydrolysis of GlcNAc-betaCD by cyclodextrin
      glycosyltransferase, and Gal-GlcNAc-betaCD by bacterial saccharifying alpha
      amylase respectively. Finally, GlcNAc-Glc3-betaCD and Gal-GlcNAc-Glc3-betaCD were
      synthesized in 5.2% and 3.5% yield when Klebsiella pneumoniae pullulanase was
      incubated with the mixture of GlcNAc-Glc(3) and betaCD, or Gal-GlcNAc-Glc3 and
      betaCD respectively. The structures of GlcNAc-Glc3-betaCD and Gal-GlcNAc-Glc3
      betaCD were analyzed by FAB-MS and NMR spectroscopy and identified as 6-O-alpha
      (6(3)-O-beta-D-N-acetylglucosaminyl-maltotriosyl)-betaCD, and 6-O-alpha-(4-O-beta
      D-galactopyranosyl-6(3)-O-beta-D-N-acetylglucosaminyl-maltotriosyl)-betaCD
      respectively.

PMID- 15849412
TI  - Effect of proline and K+ on the stimulation of cellular activities in Escherichia
      coli K-12 under high salinity.
AB  - Growth of Escherichia coli K-12 in a modified Davis minimal medium was inhibited
      under high osmolarity, but it recovered remarkably with the addition of 1 mM
      proline. The co-existence of K+ with proline enhanced the recovery of growth
      under high osmolarity more than that in the presence of proline alone. The same
      was true for the activities of respiration and glucose uptake. A similar
      supplementary effect of K+ was observed for the activities of proline uptake
      under high osmolarity. These results suggest that K+ and proline support not only
      growth but respiration and uptake of the respiratory substrate glucose in the
      cell cytoplasm when exposed to high osmolarity. External K+ almost disappeared
      with 1 h of incubation at low osmolarity, indicating that active accumulation of
      K+ in the cells occurred. On the other hand, a gradual accumulation of K+ was
      recognized at high osmolarity in the presence of 1 M NaCl, especially at > 2 h of
      incubation. This study of L-[5-3H]proline uptake in the cell cytoplasm indicates
      that proline was incorporated as a substrate of protein synthesis in the absence
      of NaCl, but was efficiently utilized as a compatible solute in the presence of
      high concentrations of NaCl.

PMID- 15849413
TI  - Visualizing nuclear migration during conidiophore development in Aspergillus
      nidulans and Aspergillus oryzae: multinucleation of conidia occurs through direct
      migration of plural nuclei from phialides and confers greater viability and early
      germination in Aspergillus oryzae.
AB  - Nuclear migration is indispensable for normal growth, differentiation, and
      development, and has been studied in several fungi including Aspergillus nidulans
      and Neurospora crassa. To better characterize nuclear movement and its
      consequences during conidiophore development, conidiation, and conidial
      germination, we performed confocal microscopy and time-lapse imaging on A.
      nidulans and Aspergillus oryzae strains expressing the histone H2B-EGFP fusion
      protein. Active trafficking of nuclei from a vesicle to a phialide and
      subsequently into a conidium provided the mechanistic basis for the formation of
      multinucleate conidia in A. oryzae. In particular, the first direct visual
      evidence on multinucleate conidium formation by the migration of nuclei from a
      phialide into the conidium, rather than by mitotic division in a newly formed
      conidium, was obtained. Interestingly, a statistical analysis on conidial
      germination revealed that conidia with more nuclei germinated earlier than those
      with fewer nuclei. Moreover, multinucleation of conidia conferred greater
      viability and resistance to UV-irradiation and freeze-thaw treatment.

PMID- 15849414
TI  - Structural characteristics of hen egg ovalbumin expressed in yeast Pichia
      pastoris.
AB  - The recombinant ovalbumin (OVA) produced in yeast Pichia pastoris was purified
      from the culture medium by anion exchange chromatography, and its structural
      characteristics were compared with those of hen egg OVA, mainly from the point of
      view of posttranslational modification. The expressed OVA consisted of two
      molecular species immmunoreactive with antibody for hen egg OVA. The two
      molecular species, 45 and 47 kDa in molecular size, were thought to correspond to
      mono-glycosylated form and di-glycosylated form respectively. The non
      glycosylated form was not produced in the system. The other posttranslational
      modifications (N-terminal acetylation and phosphorylation) observed in hen egg
      OVA were not detected in either of the molecular species. The two recombinant
      proteins displayed almost exactly the same circular dichroism and intrinsic
      tryptophan fluorescence spectra as hen egg OVA. The melting temperature, Tm,
      which was determined from the thermal unfolding curve, was almost identical in
      the two recombinant proteins, despite the difference in glycosylation levels,
      while it decreased by about 2.5 degrees C as compared with that of hen egg OVA
      (77.3 degrees C). These data indicate that the additional glycosylation to Asn
      311 in the recombinant protein does not affect protein conformation or
      thermostability.

PMID- 15849415
TI  - Purification and cDNA cloning of chloroplastic monodehydroascorbate reductase
      from spinach.
AB  - The chloroplastic isoform of monodehydroascorbate (MDA) radical reductase was
      purified from spinach chloroplasts and leaves. The cDNA of chloroplastic MDA
      reductase was cloned, and its deduced amino acid sequence, consisting of 497
      residues, showed high homology with those of putative organellar MDA reductases
      deduced from cDNAs of several plants. The amino acid sequence of the amino
      terminal of the purified enzyme suggested that the chloroplastic enzyme has a
      transit peptide consisting of 53 residues. A southern blot analysis suggested the
      occurrence of a gene encoding another isoform homologous to the chloroplastic
      isoform in spinach. The recombinant enzyme was highly expressed in Eschericia
      coli using the cDNA, and purified to a homogeneous state with high specific
      activity. The enzyme properties of the chloroplastic isoform are presented in
      comparison with those of the cytosolic form.

PMID- 15849416
TI  - Emission mechanism of floral scent in Petunia axillaris.
AB  - The mechanism of floral scent emission was studied in Petunia axillaris, a plant
      with a diurnal rhythm of scent output. The emission rate of each volatile
      compound oscillated in synchrony with its endogenous concentration, so that the
      intensity of the floral scent appeared to be determined by the endogenous
      concentrations. The composition of major volatiles in the flower tissue and the
      flower headspace showed characteristic differences. A negative correlation was
      found between the boiling points of the volatile compounds and the ratio of their
      emitted and endogenous concentrations, indicating that the composition of the
      floral scent depends directly on the endogenous composition of the volatile
      compounds. We conclude that in P. axillaris, the physiological regulation of
      floral scent emission operates not in the vaporization process but in the control
      of the endogenous concentrations of volatiles through biosynthesis and metabolic
      conversion.

PMID- 15849417
TI  - Quantification of indole-3-acetic acid and amino acid conjugates in rice by
      liquid chromatography-electrospray ionization-tandem mass spectrometry.
AB  - A method for quantifying indole-3-acetic acid (IAA) and its conjugates with the
      six amino acids, Ala, -Asp, -Ile, -Glu, -Phe and -Val, in rice (Oryza sativa) by
      using high-performance liquid chromatography coupled with electrospray ionization
      and tandem mass spectrometry (HPLC-ESI-MS/MS) is described. Samples from the rice
      plant or callus were treated with 80% acetone in water containing 2.5 mM diethyl
      dithiocarbamate. Each extract was partially purified in C18 cartridge column for
      solid-phase extraction (SPE) and subjected to HPLC-ESI-MS/MS without converting
      the product. The detection limit was 3.8 fmol for IAA, and 0.4-2.9 fmol for the
      IAA amino acid conjugates. The method was applied to the analysis of IAA and its
      conjugates in rice seedlings, dehulled rice and calli, using 20-100 mg tissue
      samples.

PMID- 15849418
TI  - Theanine production by coupled fermentation with energy transfer employing
      Pseudomonas taetrolens Y-30 glutamine synthetase and baker's yeast cells.
AB  - Theanine was formed from glutamic acid and ethylamine by coupling the reaction of
      glutamine synthetase (GS) of Pseudomonas taetrolens Y-30 with sugar fermentation
      of baker's yeast cells as an ATP-regeneration system. Theanine formation was
      stimulated by the addition of Mn2+ to the mixture for the coupling. The addition
      of Mg2+ was less effective. In a mixture containing a larger amount of yeast
      cells with a fixed level of GS, glucose (the energy source) was consumed rapidly,
      resulting in a decrease in the final yield of theanine. On the other hand, an
      increase in GS amounts increased theanine formation in a mixture with a fixed
      amount of yeast cells. High concentrations of ethylamine enhanced theanine
      formation whereas inhibited yeast fermentation of sugar and the two contrary
      effects of ethylamine caused a high yield of theanine based on glucose consumed.
      In an improved reaction mixture containing 200 mM sodium glutamate, 1,200 mM
      ethylamine, 300 mM glucose, 50 mM potassium phosphate buffer (pH 7.0), 5 mM
      MnCl2, 5 mM AMP, 100 units/ml GS, and 60 mg/ml yeast cells, approximately 170 mM
      theanine was formed in 48 h.

PMID- 15849419
TI  - DNA-binding protein involved in the regulation of chitinase production in
      Streptomyces lividans.
AB  - A protein that binds specifically to the promoter region of chiA was purified
      from the cell lysate of Streptomyces lividans by using an affinity purification
      method. Determining the amino-terminal amino acid sequence of the purified
      protein led to cloning of a gene (cpb1) encoding the chitinase promoter-binding
      protein, Cpb1. The deduced amino acid sequence of Cpb1 showed significant
      similarity to the sequences of a group of hypothetical proteins of S. coelicolor
      that have been revealed by the genome project, and the amino-terminal region of
      Cpb1 showed similarity to the DNA-binding domains of several transcription
      factors. The Cpb1 proteins expressed in S. lividans or Escherichia coli showed
      specific binding activity to the chiA promoter. The disruption of cpb1 resulted
      in partial relief of the glucose repression of chitinase production, indicating
      that cpb1 took part in the regulation of chitinase expression in S. lividans.

PMID- 15849420
TI  - Oral administration of royal jelly facilitates mRNA expression of glial cell line
      derived neurotrophic factor and neurofilament H in the hippocampus of the adult
      mouse brain.
AB  - Royal jelly (RJ) is known to have a variety of biological activities toward
      various types of cells and tissues of animal models, but nothing is known about
      its effect on brain functions. Hence, we examined the effect of oral
      administration of RJ on the mRNA expression of various neurotrophic factors,
      their receptors, and neural cell markers in the mouse brain. Our results revealed
      that RJ selectively facilitates the mRNA expression of glial cell line-derived
      neurotrophic factor (GDNF), a potent neurotrophic factor acting in the brain, and
      neurofilament H, a specific marker predominantly found in neuronal axons, in the
      adult mouse hippocampus. These observations suggest that RJ shows neurotrophic
      effects on the mature brain via stimulation of GDNF production, and that enhanced
      expression of neurofilament H mRNA is involved in events subsequently caused by
      GDNF. RJ may play neurotrophic and/or neuroprotective roles in the adult brain
      through GDNF.

PMID- 15849421
TI  - Cloning of cDNAs encoding isopropylmalate dehydrogenase from Arabidopsis thaliana
      and accumulation patterns of their transcripts.
AB  - Isopropylmalate dehydrogenase (IPMDH) is an enzyme in the leucine biosynthetic
      pathway. We isolated three IPMDH ORF sequences from Arabidopsis thaliana, and
      genes corresponding to these ORF sequences were designated AtIMD1, AtIMD2, and
      AtIMD3. Deduced amino acid sequences of the three genes contain a putative
      transit-peptide for plastidic localization. AtIMD1, AtIMD2, and AtIMD3 were able
      to complement a leu2 mutant of yeast, suggesting that these genes encode
      functional IPMDH. RT-PCR analysis revealed different tissue specificity of
      transcript accumulation for the three genes.

PMID- 15849422
TI  - Characterization and antifungal activity of gazyumaru (Ficus microcarpa) latex
      chitinases: both the chitin-binding and the antifungal activities of class I
      chitinase are reinforced with increasing ionic strength.
AB  - Three chitinases, designated gazyumaru latex chitinase (GLx Chi)-A, -B, and -C,
      were purified from the latex of gazyumaru (Ficus microcarpa). GLx Chi-A,-B, and 
      C are an acidic class III (33 kDa, pI 4.0), a basic class I (32 kDa, pI 9.3), and
      a basic class II chitinase (27 kDa, pI > 10) respectively. GLx Chi-A did not
      exhibit any antifungal activity. At low ionic strength, GLx Chi-C exhibited
      strong antifungal activity, to a similar extent as GLx Chi-B. The antifungal
      activity of GLx Chi-C became weaker with increasing ionic strength, whereas that
      of GLx Chi-B became slightly stronger. GLx Chi-B and -C bound to the fungal cell
      walls at low ionic strength, and then GLx Chi-C was dissociated from them by an
      escalation of ionic strength, but this was not the case for GLx Chi-B. The chitin
      binding activity of GLx Chi-B was enhanced by increasing ionic strength. These
      results suggest that the chitin-binding domain of basic class I chitinase binds
      to the chitin in fungal cell walls by hydrophobic interaction and assists the
      antifungal action of the chitinase.

PMID- 15849423
TI  - Enzymatic and genetic characterization of firefly luciferase and Drosophila
      CG6178 as a fatty acyl-CoA synthetase.
AB  - Recently we found that firefly luciferase is a bifunctional enzyme, catalyzing
      not only the luminescence reaction but also long-chain fatty acyl-CoA synthesis.
      Further, the gene product of CG6178 (CG6178), an ortholog of firefly luciferase
      in Drosophila melanogaster, was found to be a long-chain fatty acyl-CoA
      synthetase and dose not function as a luciferase. We investigated the substrate
      specificities of firefly luciferase and CG6178 as an acyl-CoA synthetase
      utilizing a series of carboxylic acids. The results indicate that these enzymes
      synthesize acyl-CoA efficiently from various saturated medium-chain fatty acids.
      Lauric acid is the most suitable substrate for these enzymes, and the product of
      lauroyl CoA was identified with matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry (MALDI-TOF-MS). Phylogenetic analysis indicated that
      firefly luciferase and CG6178 genes belong to the group of plant 4-coumarate:CoA
      ligases, and not to the group of medium- and long-chain fatty acyl-CoA
      synthetases in mammals. These results suggest that insects have a novel type of
      fatty acyl-CoA synthetase.

PMID- 15849424
TI  - Clinical efficacy of apple polyphenol for treating cedar pollinosis.
AB  - A double-blind comparative study was conducted on cedar pollinosis patients in
      order to evaluate the treatment efficacy of apple polyphenol (Ap). Ap was
      administered (500 mg) once daily for 12 weeks, starting about 2 weeks prior to
      cedar pollen dispersion. Pollinosis symptoms during the study were evaluated
      according to the classification in the guidelines for allergic rhinitis diagnosis
      and treatment. The results show that the sneezing score was significantly lower
      for the Ap group than with the placebo group during the early period of pollen
      dispersion and during the main dispersion period. In addition, no adverse
      reactions were induced by Ap during the study. These results suggest that Ap may
      alleviate the symptoms of cedar pollinosis.

PMID- 15849425
TI  - Synthesis of D-allose fatty acid esters via lipase-catalyzed regioselective
      transesterification.
AB  - The acylation of the rare sugar, D-allose (the C-3 epimer of D-glucose), with
      fatty acid vinyl esters was successfully carried out using Candida antarctica
      lipase in acetonitrile at 45 degrees C to give D-allose 6-alkanoates with high
      regioselectivity in good yields.

PMID- 15849426
TI  - Synthesis of a methylene analog of 5-amino-1-beta-D-ribofuranosylimidazole-4
      carboxamide monophosphate (ZMP).
AB  - A novel ZMP analog 3 was synthesized from inosine in 10 steps, and exhibited
      small but significant inhibitory activity toward protein kinase C.

PMID- 15849427
TI  - Difructose anhydrides III and IV equally promote calcium absorption from the
      luminally perfused rat small intestine.
AB  - We examined the effects of di-D-fructose anhydride (DFA) III and IV on Ca
      absorption in luminally perfused segments of the small intestine in anesthetized
      rats. The calcium absorption rate with perfusion of 10 mmol/l CaCl2 was similarly
      increased by addition of 100 mmol/l DFAIII or IV, and these promotive effects of
      both DFAs were pronounced at perfusion rate of 0.15 ml/min than at 0.3 ml/min.
      The promotive effects were higher in the duodenojejunum than in the ileum.

PMID- 15849428
TI  - Purification and characterization of chitinase B from moderately thermophilic
      bacterium Ralstonia sp. A-471.
AB  - Chitinase B was purified from a culture medium of Ralstonia sp. A-471 by
      precipitation with (NH4)2SO4 and column chromatography with DEAE-Toyopearl 650 M
      and Sephacryl S-200. The purified enzyme was homogeneous on SDS-PAGE. The
      molecular weight was 45,000 by SDS-PAGE. The optimum pH was 5.0 and stable pH was
      from 5.0 to 10.0. In the early stage of the reaction, chitinase B produced beta
      anomer of (GlcNAc)2 from the substrate (GlcNAc)6, whereas (GlcNAc)4 produced
      almost at equilibrium, indicating that the enzyme predominantly hydrolyzes the
      second glycosidic linkage from the nonreducing end of (GlcNAc)6.

PMID- 15849429
TI  - Preparation of elastic silk sericin hydrogel.
AB  - This paper reports a preparation method for silk sericin hydrogel using the
      Sericin-hope silkworm, whose cocoons consist almost exclusively of sericin.
      Sericin solution, prepared from Sericin-hope cocoons, contains intact sericin and
      forms elastic hydrogels with the addition of ethanol. The sericin hydrogel can be
      prepared without crosslinking by chemicals or irradiation and might be usable as
      a naturally occurring biomaterial.

PMID- 15849430
TI  - Immunological properties of sedoheptulose-1,7-bisphosphatase from Chlamydomonas
      sp. W80.
AB  - Here we report on the production of functional recombinant SBPase of
      Chlamydomonas sp. W80 in Escherichia coli and the one-step purification of a
      polyhistidine-tagged fusion protein. The polyclonal antibody was raised against
      purified recombinant enzyme and cross-reacted with crude SBPase from
      Chlamydomonas, spinach, tobacco, and Arabidopsis leaves. Further, we investigated
      the levels of protein and activity of SBPase in different tissues of Arabidopsis
      plants.

PMID- 15849431
TI  - Tissue distribution, synthesis stage, and ethylene induction of pineapple (Ananas
      comosus) chitinases.
AB  - We examined the tissue distribution, synthesis stage, and ethylene induction of
      three types of pineapple chitinase using chitinase activity gel and immunoblot
      analysis. Type A (acidic class III) exists in all tissues, while type B (weakly
      basic class I, which has strong antifungal activity) and type C (acidic class I)
      are localized mainly in the leaf and stem. In a pericarp, type A exists at all
      stages during fruit development, while type B and type C exist only at the early
      stage. Synthesis of type A is induced by ethylene, while that of types B and C is
      not affected by it. These results suggest that the physiological roles of these
      three types of chitinase in pineapple are different.

PMID- 15849432
TI  - Time-course characteristics for the digestion of endogenous as well as exogenous
      protein in the small intestine: a case study with rats fed a [15N]-soy protein
      isolate.
AB  - A study was conducted to evaluate a net value of exogenous (dietary) protein
      nutrition in rats fed a [15N]-labeled soy protein isolate (SPI). Although [15N]
      SPI-derived nitrogen reached a plateau 2 hr after feeding, it accounted for only
      a half of the total nitrogen in the small intestine. 15N was confirmed that was
      normally transported to liver, kidney, spleen, and brain. The present study
      reveals the large degree of participation of endogenous proteins in dietary SPI
      during small-intestinal digestion.

PMID- 15849433
TI  - Involvement of Saccharomyces cerevisiae Pdr5p ATP-binding cassette transporter in
      calcium homeostasis.
AB  - Deletion of PDR5 gene (Deltapdr5) in Saccharomyces cerevisiae led to increased
      resistance to calcium. The cellular Ca2+ level in the presence of high calcium as
      estimated by reporter assay in Deltapdr5 cells was significantly lower than that
      in wild-type cells. Membrane Pdr5p levels diminished rapidly during incubation
      with high calcium in a manner dependent on calcineurin and Pep4p, suggesting a
      feedback regulatory mechanism for Pdr5p abundance.

PMID- 15849434
TI  - Identification of Rab GTPase-activating protein-like protein (RabGAPLP) as a
      novel Alix/AIP1-interacting protein.
AB  - Alix/AIP1 is a multifunctional adaptor protein involved in endocytosis, cell
      adhesion, and cell death. By yeast two-hybrid screening we identified a novel
      Alix/AIP1-interacting protein named Rab GTPase-activating protein-like protein
      (RabGAPLP). Interaction between Alix and RabGAPLP was confirmed by pull-down
      assays using fusion proteins of either glutathione-S-transferase (GST) or chitin
      binding domain (CBD) and lysates of cultured mammalian cells expressing the
      respective proteins. Partial colocalization of FLAG-tagged RabGAPLP and green
      fluorescent protein (GFP)-fused Alix was observed at cell edges and filopodia
      like structures by fluorescence confocal laser scanning microscopic analysis. The
      identity of RabGAPLP to merlin-associated protein (MAP), one of the interacting
      partners of neurofibromatosis type 2 (NF2) tumor suppressor gene product
      (merlin), implies cross-talk of membrane traffic and cell adhesion.

PMID- 15849435
TI  - Efficacy of colestimide coadministered with atorvastatin in japanese patients
      with heterozygous familial hypercholesterolemia (FH).
AB  - BACKGROUND: Colestimide, a 2-methylimidazole-epichlorohydrin polymer, is a new
      bile-acid-sequestering resin, that is 4-fold as powerful at lowering low-density
      lipoprotein cholesterol (LDL-C) as the conventional resin (cholestyramine).
      Moreover, colestimide has excellent patient compliance because it is available in
      tablet form. METHODS AND RESULTS: The clinical efficacy of colestimide
      coadministered with atorvastatin on lipid and apolipoprotein concentrations was
      examined in 15 patients (M/F=10/5, mean+/-SE age=54+/-9 years) with heterozygous
      familial hypercholesterolemia (FH). After a period of wash-out of any lipid
      lowering drugs, atorvastatin (20-40 mg) was administered to patients for at least
      8 weeks, and then 3 g of colestimide was administered for a further 8 weeks.
      Total and LDL-C significantly (<0.0001) decreased by 35% from 361 to 233 mg/dl
      and 41% from 274 to 161 mg/dl, respectively. Addition of colestimide caused a
      further significant 12% and 20% reduction, respectively, from the initial values
      to 205 and 129 mg/dl, respectively. Colestimide was also effective in reducing
      serum LDL-C concentrations in heterozygous FH patients with hypertriglyceridemia
      (triglycerides>or=150 mg/dl). CONCLUSIONS: When monotherapy with atorvastatin is
      insufficient to treat severely hypercholesterolemic patients, such as those with
      heterozygous FH, colestimide acts to reinforce the action of statins.

PMID- 15849436
TI  - Relationship between serum lipoprotein(a) concentrations and coronary vasomotion
      in coronary spastic angina.
AB  - BACKGROUND: Elevated lipoprotein(a) (Lp(a)) concentrations are reported to impair
      endothelium-dependent vasodilatation of the epicardial coronary artery. However,
      the effects on vasomotor abnormalities in coronary spastic angina (CSA) have not
      been thoroughly investigated. METHODS AND RESULTS: In the present study 80 sites
      of spasm (spastic sites) without significant organic stenosis (% diameter
      stenosis <50%) were assessed in 80 patients with CSA diagnosed by intracoronary
      ergonovine (EM) test. Spastic sites were divided into 2 groups: Group 1 included
      30 sites provoked by the full dose (=50 microg) of EM, and Group 2 included 50
      sites provoked with less than 50 microg (34.7+/-8.2 microg). Control subjects
      (n=22) did not show coronary spasm with the EM test. Serum Lp(a) concentrations
      were measured in all patients. Group 2 had a significantly greater basal coronary
      artery tone in the spastic sites than Group 1 (p<0.001). Lp(a) level in Group 2
      was significantly higher compared with both the control group and Group 1 (p<0.05
      by analysis of variance). Multivariate analysis confirmed that only serum Lp(a)
      concentration was associated with low-dose EM spasm provocation. CONCLUSIONS:
      Serum Lp(a) concentration could be a marker for high disease activity in CSA.

PMID- 15849437
TI  - Significance of neutrophil counts after reperfusion therapy in patients with a
      first anterior wall acute myocardial infarction.
AB  - BACKGROUND: Previous studies have demonstrated that an elevated neutrophil count
      on admission is associated with a higher risk of adverse events after acute
      myocardial infarction (AMI). However, the significance of the neutrophil count
      after reperfusion therapy has not been elucidated. METHODS AND RESULTS: The
      association of the neutrophil count on admission and days 2 and 3 with peak
      creatine kinase (CK) concentration, ST-segment resolution (a marker of myocardial
      tissue-level reperfusion), and left ventricular (LV) function at predischarge
      were examined in 122 patients (102 men, 20 women, mean age 61+/-11 years) with a
      first anterior wall AMI. Neutrophil counts were increased on day 2 and decreased
      on day 3 compared with admission (8,768+/-3,005 mm3, 6,617+/-2,424 mm3, and
      7,725+/-3,388 mm3, respectively). Patients with ST-segment resolution (n=52) had
      lower neutrophil counts on days 2 and 3 than those without it (n=70), but
      neutrophil counts on admission did not differ significantly between patients with
      and without ST-segment resolution. Neutrophil counts on admission and days 2 and
      3 were weakly but significantly correlated with peak CK concentration (r=0.31,
      p=0.0004; r=0.43, p<0.0001; r=0.32, p=0.003, respectively) and with LV ejection
      fraction at predischarge (r=-0.18, p=0.04; r=-0.26, p=0.003; r=-0.27, p=0.003;
      respectively). CONCLUSION: The neutrophil count after reperfusion is weakly but
      significantly correlated with infarct size, myocardial tissue-level reperfusion,
      and LV function at predischarge in a first anterior wall AMI. These correlations
      were slightly stronger than the correlations with the neutrophil count on
      admission.

PMID- 15849438
TI  - Relationship between myocardial injury and soluble P-selectin in non-ST elevation
      acute coronary syndromes.
AB  - BACKGROUND: The relationships among troponin concentration, early phase
      coagulation activation and soluble P-selectin concentration was evaluated in this
      study. METHODS AND RESULTS: Troponin-l, soluble P-selectin, von Willebrand factor
      (vWF), fibrinogen, plasminogen, plasminogen activator inhibitor 1 (PAI-1) and
      tissue plasminogen activator (t-PA) concentrations of 202 consecutive patients
      with non-ST elevation acute coronary syndrome (NSTE-ACS) were measured at the
      time of admission. Patients were classified into 2 groups as troponin-negative
      (<0.2 ng/ml, n=129) or positive (>or=0.2 ng/ml, n=73). Soluble P-selectin
      concentrations were found to be higher (p<0.001) and correlated with troponin
      concentrations (r=0.313, p<0.005) in troponin-positive patients with NSTE-ACS. In
      these patients fibrinogen (p<0.001), plasminogen (p<0.001) and PAI-1 (p<0.026)
      concentrations were higher and t-PA concentrations were lower (p<0.013) and all
      these parameters correlated with P-selectin concentrations (p<0.001). There was
      no difference between the groups according to vWF concentrations (p=0.379).
      Soluble P-selectin concentrations were found to be an independent predictor of
      troponin positivity (beta=0.295, odds ratio =1.05, p<0.001). Analysis of
      regression revealed a significant effect of troponin on soluble P-selectin
      concentrations (r=0.52, r2=0.27, p<0.001). CONCLUSIONS: The results suggest that
      higher soluble P-selectin concentrations might be involved in increased
      coagulation activation and myocardial injury development in patients with NSTE
      ACS.

PMID- 15849439
TI  - Impact of right atrial-left ventricular dual-chamber permanent pacing in patients
      with severely symptomatic hypertrophic obstructive cardiomyopathy.
AB  - BACKGROUND: Effective alternatives to surgical myectomy for patients with
      symptomatic hypertrophic obstructive cardiomyopathy (HOCM) remain unestablished.
      Dual-chamber (DDD) pacing was evaluated in these patients using right atrial (RA)
      and epicardial left ventricular (LV) leads. METHODS AND RESULTS: In 6 patients
      with HOCM refractory to medical therapy and conventional RA-right ventricular
      (RV) DDD pacing, we implanted DDD pacemakers using RA and epicardial LV leads.
      The baseline intraventricular pressure gradient before pacemaker implantation was
      103+/-44 mmHg. The pressure gradient decreased significantly to 8+/-16 mmHg by
      temporary RA-LV DDD pacing (p=0.006), while it decreased only to 68+/-25 mmHg by
      temporary RA-RV pacing (NS). It was nearly eliminated to 1+/-2 mmHg (p=0.027) 3
      months after RA-LV DDD pacemaker implantation. LV end-diastolic pressure, cardiac
      index and systolic aortic pressure did not change significantly. New York Heart
      Association class improved in all patients (p=0.023). Brain and atrial
      natriuretic peptide concentrations, respectively 516+/-286 and 143+/-34 pg/ml at
      baseline, decreased significantly to 230+/-151 and 93+/-44 pg/ml 3 months after
      implantation (p=0.027 and 0.028). CONCLUSION: RA-LV DDD pacemaker implantation is
      a useful option for patients with symptomatic HOCM.

PMID- 15849440
TI  - In vivo quantitative tissue characterization of angiographically normal coronary
      lesions and the relation with risk factors: a study using integrated backscatter
      intravascular ultrasound.
AB  - BACKGROUND: Autopsy studies have shown atherosclerotic changes in
      angiographically normal coronary lesions (ANCL), and conventional intravascular
      ultrasound shows intimal thickening in these lesions, but cannot differentiate
      the lipid core. Accurate characterization of ANCL is essential to prevent
      progression to coronary artery disease. METHODS AND RESULTS: ANCL (n=120) were
      analyzed by integrated backscatter intravascular ultrasound (IB-IVUS) in 30
      patients with stable angina pectoris. Of the 120 arterial segments analyzed by IB
      IVUS, 78 (65%) showed lipid cores of 0.69+/-0.35 mm2 with fibrous caps of 200+/
      100 microm thick, 44 (37%) had intimal hyperplasia with a thickness of 350+/-100
      microm, and 65 (54%) showed fibrosis in the intimal wall without lipid core with
      a thickness of 450+/-150 microm. The diabetes mellitus (DM) group (n=14) had
      significantly (p<0.05) bigger lipid cores (0.62+/-0.38 mm2) and thinner intimal
      hyperplasia (100+/-100 microm) compared with the non-DM group (0.31+/-0.33 mm2,
      150+/-150 microm, respectively). The hypertension (HT) group (n=23) had
      significantly more intimal hyperplasia (150+/-150 microm) compared with the non
      HT group (50+/-100 microm). Hyperlipidemia (n=16) or smoking (n=6) did not
      significantly affect tissue characteristics. CONCLUSION: IB-IVUS showed various
      types of plaque in ANCL and the plaque characteristics were affected by DM and
      HT. The results provide new clinical insight into the early stage of human
      coronary atherosclerosis.

PMID- 15849441
TI  - Myocardial perfusion imaging using adenosine triphosphate stress multi-slice
      spiral computed tomography: alternative to stress myocardial perfusion
      scintigraphy.
AB  - BACKGROUND: The present study was designed to: (i) detect myocardial ischemia in
      contrast enhanced multi-slice spiral computed tomography (CE-MSCT) using
      adenosine triphosphate (ATP) pharmacological stress test; and (ii) evaluate the
      potential of ATP stress CE-MSCT in a clinical setting. METHODS AND RESULTS:
      Twelve patients underwent ATP stress CE-MSCT and stress thallium-201 myocardial
      perfusion scintigraphy (MPS) and 9 of the patients received conventional coronary
      angiography (CAG). Dual CE-MSCT scans were performed for stress and rest images,
      with and without intravenous infusion of ATP (0.16 mg.kg-1.min-1) at intervals of
      20 min. Myocardial perfusion and coronary artery were visually evaluated using
      MSCT and compared the results obtained from MPS and CAG. Of 36 territories,
      stress images of CE-MSCT described 26 hypo-perfusion areas and MPS described 22
      redistributions. The agreement between MSCT and MPS was 83% (30/36, p<0.05). In
      141 coronary artery segments of 9 patients undergoing CAG, rest images of CE
      MSCT, which had significantly higher assessability than stress images (89% vs
      48%, p<0.05), described 76% (13/17) of culprit coronary stenoses. CONCLUSIONS:
      Although CT-angiography should be currently assessed using rest images, ATP
      stress CE-MSCT can describe both ATP-induced myocardial ischemia and coronary
      artery stenoses in patients with coronary artery disease.

PMID- 15849442
TI  - Value of pharmacologic stress myocardial perfusion imaging for preoperative risk
      stratification for aortic surgery.
AB  - BACKGROUND: Aortic surgery is an invasive, high-risk noncardiac procedure and the
      patients who require it have a high prevalence of coronary artery disease.
      Therefore, preoperative risk stratification for this subset is essential. METHODS
      AND RESULTS: To assess the perioperative risk for aortic surgery, pharmacologic
      stress single-photon emission computed tomography (SPECT) was performed in 302
      patients: aortic dissection in 56, thoracic aortic aneurysm in 124, and abdominal
      aortic aneurysm in 122. Not only was the presence or absence of perfusion defects
      analyzed, but also the 20-segment model. Pharmacologic thallium SPECT revealed
      negative findings in 210 patients and positives in 92. Perioperative cardiac
      events occurred in 9 patients: 7 occurred in patients with positive SPECT, and in
      only 2 of those with negative SPECT (2/210 vs 7/92; p<0.05). Multivariate
      analysis using logistic regression model revealed that a summed stress
      score>or=14 was the most important factor to identify patients who subsequently
      had perioperative cardiac events. CONCLUSIONS: Pharmacologic stress SPECT has
      significant value in the risk stratification of patients before aortic surgery.
      In patients with positive SPECT, an aggressive approach to reduce the
      preoperative risk is necessary, whereas aortic surgery can be performed safely in
      patients with negative SPECT.

PMID- 15849443
TI  - Effects of exercise training on left ventricular function evaluated by the Tei
      index in patients with myocardial infarction.
AB  - BACKGROUND: This study investigated the influence of exercise training on left
      ventricular (LV) function in patients with acute myocardial infarction (AMI)
      using a new index of cardiac function, the Tei index. METHODS AND RESULTS: The
      study enrolled 53 consecutive patients (36 males, 17 females; mean age: 65+/-10
      years) with AMI. Exercise training was performed for 6 months; peak VO2 and the
      Tei index were measured at the start of the cardiac rehabilitation program and 1,
      3, and 6 months later. The peak VO2 improved from 14.3+/-3.3 to 18.5+/-5.2 ml.min
      -1.kg-1 after 6 months (p<0.01). Although there were no significant changes in LV
      ejection fraction over the 6 months, the Tei index improved from 0.50+/-0.18 to
      0.41+/-0.19 (p<0.05). When the DeltaTei index was compared among the 3 groups
      classified by the Tei index at baseline, the values improved in the groups with
      high/slightly high values compared with the normal group. CONCLUSION: Both
      cardiac function, as evaluated by the Tei index, and exercise capacity improved
      after exercise training in patients with AMI. The greater improvement was seen in
      the population with the higher value (lower cardiac function) according to this
      index.

PMID- 15849444
TI  - Link between SCN5A mutation and the Brugada syndrome ECG phenotype: simulation
      study.
AB  - BACKGROUND: The specific changes in the gating kinetics of the sodium current
      (I(Na)) responsible for its phenotype have remained to be elucidated. In the
      present study the effect of changes in the gating kinetics of I(Na) on early
      repolarization (ER) and initiation of phase 2 reentry (P2R) were evaluated in a
      theoretical epicardial ventricular fiber model. METHODS AND RESULTS: Miyoshi
      I(CaL) was incorporated into the modified Luo-Rudy dynamic (LRd) model.
      Dispersion at Ito-density was set within a theoretical fiber composed of serially
      arranged epicardial cells with gap junctions. The following changes in I(Na)
      kinetics were made: (1) a-10 mV shift in steady-state inactivation, (2) a+10 mV
      shift in steady-state activation curve, (3) a small inactivation time constant
      (DEC); P2R and ER were observed. A conduction disturbance within the fiber was
      simulated and only when the I(Na)-density was decreased did DEC, especially, show
      a marked increase in the likelihood of causing ER and P2R. Conduction disturbance
      significantly increased the likelihood causing ER or P2R. CONCLUSIONS: In this
      one-dimension model with Ito-density dispersion, DEC-I(Na) precipitates I(Na)
      blocker inducible ER. This suggests that the characteristic ST-segment elevation
      in the Brugada syndrome with SCN5A mutation can be interpreted in part by DEC
      I(Na). Concomitant conduction disturbance may be required to cause P2R at
      physiological Ito density.

PMID- 15849445
TI  - Combined effects of nifekalant and lidocaine on the spiral-type re-entry in a
      perfused 2-dimensional layer of rabbit ventricular myocardium.
AB  - BACKGROUND: Spiral re-entry plays the principal role in the genesis of
      ventricular tachycardia and ventricular fibrillation (VT/VF). The specific I(Kr)
      blocker, nifekakant (NIF) has, often in combination with lidocaine (LID),
      recently been used in Japan to prevent recurrent VT/VF, but the combined effects
      of these drugs on spiral re-entry had never been investigated. METHODS AND
      RESULTS: A ventricular epicardial sheet was obtained from 13 Langendorff-perfused
      rabbit hearts by means of a cryoprocedure, and epicardial excitations were
      analyzed with a high-resolution optical mapping system. Nifekakant (0.5
      micromol/L) caused significant prolongation of action potential duration (APD)
      and LID (3 micromol/L) attenuated the APD prolongation without affecting the
      conduction velocity. VT were induced in 6 hearts by cross-field stimulation, and
      single- or double-loop spirals circulating around variable functional block lines
      were visualized during the VT. Nifekakant reduced VT cycle length and caused
      early termination in association with destabilization of the spiral dynamics
      (prolongation of functional block line, frequent local conduction block, and
      extensive meandering). These modifications of spiral-type re-entrant VT by NIF
      were prevented by addition of LID. CONCLUSIONS: The effects of NIF on the spiral
      excitations are reversed by LID. This interaction should be taken into account
      when these drugs are used in combination to treat VT/VF.

PMID- 15849446
TI  - Cardiovascular circulation and hepatic perfusion of pigs in 4-dimensional films
      evaluated by 256-slice cone-beam computed tomography.
AB  - BACKGROUND: In both cardiac and hepatic disorders it is desirable to accurately
      visualize the direction and scale of blood flow in the whole organ in pulsating 3
      dimensional (D) images, which are known as 4-D images. METHODS AND RESULTS: The
      present study used 256-slice cone-beam computed tomography (CT) (Athena, Sony
      Toshiba) at one rotation per second and a section thickness of 0.5 mm to show the
      dynamics of cardiovascular circulation and hepatic perfusion by contrast
      injection in 4-D films of pigs. Four pigs (20 kg each) were anesthetized with
      isoflurane. The distal tips of the catheters were positioned in the inferior vena
      cava (IVC) (pigs 1-3) and in the proper hepatic artery (pig 4). Volumetric
      scanning and injection of contrast material were started simultaneously and
      continued for 25 s with image reconstruction at 1-s intervals. In pigs 1-3, 4-D
      filming revealed the dynamics of cardiovascular circulation, first in the IVC,
      followed by the right ventricle and pulmonary artery, then the left ventricle,
      left atrium, pulmonary vein, and finally, the right heart disappeared and only
      the left heart and aorta remained visible. In pig 4, the hepatic arterial trees,
      followed by the venous trees, could be easily visualized in turn on the 4-D
      images. CONCLUSIONS: This technology successfully demonstrated cardiovascular
      circulation and hepatic perfusion in 4-D and will have clinical applicability.

PMID- 15849447
TI  - Ischemia-induced norepinephrine release, but not norepinephrine-derived free
      radicals, contributes to myocardial ischemia-reperfusion injury.
AB  - BACKGROUND: Norepinephrine (NE)-derived free radicals may contribute to myocyte
      injury after ischemia -reperfusion, so the influence of sympathetic denervation
      on myocardial ischemia - reperfusion injury was investigated in the present
      study. METHODS AND RESULTS: Cardiac sympathetic denervation was produced in
      Wistar rats by a solution of 10% phenol 1 week before ischemia. Atenolol (0.5
      mg/kg) was intravenously administered 10 min before the coronary occlusion. The
      left coronary artery was occluded for 30 min and thereafter reperfused. Cardiac
      interstitial fluid was collected by a microdialysis probe and free radicals in
      dialysate were determined by electron paramagnetic resonance (EPR) spin trapping,
      using 5,5-dimethyl-1-pyrroline-N-oxide as a spin trap. The ratio of infarct size
      to the ischemic area at risk (I/R) was decreased in both the phenol and atenolol
      groups compared with control (28.5+/-11.3, 31.8+/-10.7 vs 50.6+/-14.7%, p<0.05).
      During the coronary occlusion, concentrations of interstitial NE increased
      markedly in the control and atenolol groups, but was unchanged in the phenol
      group. EPR signal intensity (relative value to internal standard) was maximal at
      1 h after reperfusion and was similar in the phenol and control groups (0.32+/
      0.15 vs 0.45+/-0.19). CONCLUSIONS: Cardiac denervation protected myocyte against
      ischemia-reperfusion injury through decreasing direct NE toxicity, but not
      through decreasing NE-derived free radicals.

PMID- 15849448
TI  - Mechanisms of combined treatment with celiprolol and candesartan for ventricular
      remodeling in experimental heart failure.
AB  - BACKGROUND: Both beta-adrenergic blockers and angiotensin-II receptor blockers
      were reported to improve the prognosis of patients with heart failure, but the
      efficacy of combination therapy with these agents has not been fully elucidated.
      Also the efficacy of celiprolol, a beta1-selective adrenoceptor antagonist with
      partial beta2-agonist properties, for heart failure treatment is still
      controversial. We examined the cardioprotective effects and mechanisms of the
      therapy with celiprolol or candesartan, an angiotensin-II receptor blockers and
      their combination in heart failure induced by isoproterenol (ISO). METHODS AND
      RESULTS: ISO 300 mg/kg was injected in rats to produce heart failure. Two months
      after the injection, the ISO-injected rats were divided into 4 groups (8 rats
      each) and treated for 4 weeks as follows: (a) vehicle; (b) celiprolol 10 mg/kg
      per day (BB); (c) candesartan 0.2 mg/kg per day (ARB); and (d) their combination
      BB+ARB. ISO significantly elevated left ventricular (LV) end-diastolic pressure,
      decreased peak-negative dP/dt and LV ejection fraction. BB and ARB similarly
      ameliorated cardiac dysfunction due to ISO, but BB+ARB were more potent than the
      individual therapies. Separately, ARB preserved the histological structure in LV
      myocardium. In contrast, BB ameliorated calcium handling, as shown by the
      increased ratio of SERCA2 to phospholamban protein, despite having little effect
      on the histology. CONCLUSION: Both celiprolol and candesartan showed
      cardioprotective effects in this heart failure model. The potential use of the
      combination treatment in heart failure might result in a synergistic effect
      through the different cardioprotective mechanisms of celiprolol and candesartan.

PMID- 15849449
TI  - Effect of L-arginine on collagen of high flow-induced pulmonary arterial
      remodeling.
AB  - BACKGROUND: Pulmonary hypertension (PH) is a common complication of congenital
      heart disease and pulmonary vascular structural remodeling due to the high
      pulmonary blood flow is considered as the key pathologic process. In the present
      study the effects of L-arginine on the collagen metabolism of pulmonary arteries
      in rats with high pulmonary blood flow-induced PH were investigated to elucidate
      its mechanism. METHODS AND RESULTS: The rat model of PH was established with an
      abdominal aorta and inferior vena cava shunt. L-arginine (1 g/kg per day) was
      given directly into the stomachs of the rats with the shunt (L-arginine+shunt
      group) and 11 weeks later, the pulmonary hemodynamics were studied. Collagen I
      and collagen III expressions were detected by immunohistochemical assay. The
      expressions of procollagen I mRNA, procollagen III mRNA, the tissue inhibitor of
      metalloproteinase-1 mRNA and the matrix metalloproteinase-1 mRNA were detected by
      in situ hybridization. The expressions of pulmonary artery collagen I, collagen
      III, procollagen I mRNA and procollagen III mRNA in the shunt rats were obviously
      elevated compared with the control rats (p<0.01). The positive signals were
      mainly located in the media and adventitia of median and small pulmonary
      arteries. The expressions of the pulmonary artery tissue inhibitor of
      metalloproteinase-1 mRNA, metalloproteinase-1 mRNA and the ratio of tissue
      inhibitor of metalloproteinase-1/metalloproteinase-1 were elevated in the shunt
      rats (p<0.01). However, the expressions of pulmonary artery collagen I, collagen
      III, procollagen I mRNA and procollagen III mRNA were significantly reduced in
      the shunt rats of the L-arginine group (p<0.01). L-arginine also downregulated
      the expressions of tissue inhibitor of metalloproteinase-1 mRNA and
      metalloproteinase-1 mRNA, as well as the ratio of tissue inhibitor of
      metalloproteinase-1/metalloproteinase-1 (p<0.05). CONCLUSIONS: L-arginine can
      reduce the synthesis of extracellular matrix-collagen and increase its
      degradation, thus having an important modulating effect on pulmonary vascular
      matrix remodeling induced by high pulmonary blood flow.

PMID- 15849450
TI  - Effort angina in a middle-aged woman with abnormally high levels of serum high
      density lipoprotein cholesterol: a case of cholesteryl-ester transfer protein
      deficiency.
AB  - A 54-year-old female was admitted to hospital complaining of oppressive anterior
      chest pain during exercise. Treadmill exercise ECG testing showed significant
      ischemic ECG changes, and electron-beam computed tomography demonstrated patchy
      calcifications in the coronary artery. Coronary angiography revealed a
      significant stenotic lesion of the right coronary artery. On routine
      investigations, no classical coronary risk factors were found, although a very
      high concentration (209 mg/dl) of high-density lipoprotein cholesterol (HDL-C)
      was detected. The serum concentration of cholesteryl-ester transfer protein
      (CETP), which plays a central role in the reverse cholesterol transport system,
      was measured and found to be less than the measurable minimum. The patient showed
      one of the typical genetic CETP mutations (intone 14 splicing defect), and her
      lipid profile was improved by administration of probucol for 3 months. A very
      high concentration of HDL-C with a defect of CETP activity may be a specific
      biochemical indicator pointing to an increased risk of premature coronary artery
      disease, and the lipid profile can be improved by use of lipid-lowering drugs.

PMID- 15849451
TI  - Temporary overdriving pacing as an adjunct to antiarrhythmic drug therapy for
      electrical storm in acute myocardial infarction.
AB  - A-55-year-old man with diabetes mellitus was admitted to hospital because of
      chest pain. He was diagnosed as anterior acute myocardial infarction and treated
      with stent placement. After 7 days, ventricular fibrillation occurred because of
      a subacute reocclusion and balloon angioplasty was performed. Despite reperfusion
      therapy, intraaortic balloon pumping, antiarrhythmic drugs and beta-blocker,
      ventricular tachycardia or fibrillation relapsed and cardioversion was performed
      29 times during 32 h. Temporary overdrive atrioventricular sequential pacing was
      initiated and the malignant arrhythmia finally disappeared. Even after stoppage
      of 25 h overdride pacing, it never recurred. Temporary overdrive pacing is an
      easy and feasible therapy for a drug-resistant electrical storm associated with
      AMI and should be performed in the early stage.

PMID- 15849452
TI  - Increased reactive oxygen species and anti-oxidative response in mitochondrial
      cardiomyopathy.
AB  - A 60-year-old woman was admitted for treatment of congestive heart failure. She
      had been diagnosed with diabetes mellitus when she was 23 years old, and she
      began to go deaf when she was 34 years old. She showed symptoms of heart failure
      at age 51 and was diagnosed with hypertrophic cardiomyopathy. Echocardiography
      showed progressive diffuse hypokinetic motion of the left ventricle and the left
      ventricular hypertrophy had gradually regressed. A mitochondrial transition
      mutation, A3243G, was detected in her peripheral leukocytes (9%) and in those of
      her 27-year-old son, who also has diabetes and deafness. Electron microscopy of
      an endomyocardial biopsy specimen showed proliferation and swelling of the
      mitochondria, and significant generation of reactive oxygen species (ROS), as
      well as marked induction of heme oxygenase-1, which is an adaptive enzyme to
      oxidative damage, were also observed in the myocardial tissue. These observations
      were more prominent than in other patients with heart failure of different
      etiology, which suggests that the increased ROS generation and anti-oxidative
      response were involved in the development of the mitochondrial cardiomyopathy.

PMID- 15849453
TI  - Left ventricular free wall rupture in transient left ventricular apical
      ballooning.
AB  - A 79-year-old woman presented with chest pain. Her symptoms, combined with the
      results of an electrocardiogram, echocardiogram and laboratory investigations
      were compatible with an extensive acute anterior myocardial infarction. However,
      emergency coronary angiography showed no stenotic lesion in any coronary artery,
      but left ventriculography revealed apical ballooning akinesis and basal
      hyperkinesis and she was diagnosed as having transient left ventricular apical
      ballooning. After 7 days, she suddenly went into cardiopulmonary arrest because
      of cardiac tamponade. The autopsy revealed a free wall rupture. Generally, the
      prognosis in transient left ventricular apical ballooning is good; left
      ventricular free wall rupture is very rare.

PMID- 15849454
TI  - Duration of cerebrospinal fluid drainage in patients with aneurysmal subarachnoid
      hemorrhage for prevention of symptomatic vasospasm and late hydrocephalus.
AB  - The optimal duration of cerebrospinal fluid (CSF) drainage after acute aneurysm
      surgery is unclear. The association between the occurrence of symptomatic
      vasospasm or late hydrocephalus and the duration of CSF drainage was investigated
      using multiple logistic analysis in 95 consecutive patients with aneurysmal
      subarachnoid hemorrhage who underwent surgery within 72 hours after onset. The
      duration of drainage was significantly related to the occurrence of symptomatic
      vasospasm and late hydrocephalus. The cut-off values of the duration of drainage
      for preventing symptomatic vasospasm and late hydrocephalus were 11 days
      (adjusted odds ratio 0.347, 95% confidence interval 0.135-0.889, p = 0.0274) and
      6 days (adjusted odds ratio 4.86, 95% confidence interval 1.46-16.2, p = 0.0099),
      respectively. Prevention of both symptomatic vasospasm and late hydrocephalus is
      not possible without additional procedures such as cisternal irrigation using
      fibrinolytic agents.

PMID- 15849455
TI  - Proposed classification of segments of the internal carotid artery: anatomical
      study with angiographical interpretation.
AB  - The nomenclature and borders of the segments of the internal carotid artery (ICA)
      remain confusing. A classification of segments of the ICA is proposed based on
      constant anatomical structures, such as the carotid foramen and canal, the
      petrous bone, the petrolingual ligament (PLL), and the proximal and distal dural
      rings. The bilateral ICAs were dissected in 15 cadaveric head specimens using
      different neurosurgical approaches. The bilateral lacerum foramina were studied
      in five dry skulls. The bilateral segments of the ICA were also examined on
      carotid angiograms of 10 normal patients and another with the ophthalmic artery
      originating from the intracavernous portion of the ICA. The present
      classification divides the ICA into five segments in the direction of the blood
      flow. The cervical segment is extradural and extracranial, the petrous segment is
      extradural and intraosseous, the cavernous segment is interdural and
      intracavernous, the clinoidal segment is interdural and paracavernous, and the
      cisternal segment is intradural and intracisternal. The ICA did not pass through
      the lacerum foramen in any specimen. In all specimens, 1/8 to 5/8 of the lacerum
      foramen was under the deep dural layer of the cavernous sinus. The term 'lacerum
      segment' as used previously and called the 'trigeminal segment' by us cannot be
      justified. The PLL is the posterolateral border of the cavernous sinus and the
      lacerum and trigeminal segments should be included in the cavernous and petrous
      segments. The ophthalmic artery may originate from the clinoidal ICA, from the
      cavernous ICA, or from the middle meningeal artery. Instead of using the term
      'ophthalmic segment,' the term 'cisternal segment' should be used for the
      anatomically distinct ICA in the subarachnoid space. This classification should
      be minimally affected by anatomical variations.

PMID- 15849456
TI  - Hemifacial spasm following a blow to the mandible causing blunt injury to the
      peripheral facial nerve.
AB  - A 40-year-old male presented with hemifacial spasm manifesting as paroxysmal
      spontaneous twitches in the left peribuccal region persisting for 3 months. The
      symptoms began 7 days after an accident, when a signboard hit his left mandibular
      angle. Physical examination showed no trauma-related change in his face, and no
      neurological abnormality except for the twitches. Magnetic resonance imaging also
      showed no abnormalities of the facial nerve and adjacent regions.
      Electrophysiological studies showed synkinesis, so hemifacial spasm caused by
      peripheral facial nerve injury was suspect- ed. The symptoms subsided 4 months
      after the injury. Blunt injury to the facial nerve branches might cause
      hemifacial spasm.

PMID- 15849457
TI  - Large paraclinoid aneurysm with a calcified neck treated by tailored
      multimodality procedures.
AB  - A 68-year-old woman presented with a large paraclinoid aneurysm with a calcified
      neck causing visual symptoms. Direct clipping was hazardous because of severe
      calcification of the neck. Endovascular internal trapping was difficult because
      of the short distance between the neck and the origin of the posterior
      communicating artery. Proximal occlusion was likely to be less effective because
      of large collateral back flow to the aneurysm via the ophthalmic artery (OphA).
      The aneurysm was successfully treated by a combination of a high-flow bypass,
      intraoperative coil embolization of the parent artery including the origin of the
      OphA, and clipping of the internal carotid artery distal to the aneurysm.
      Paraclinoid aneurysms may be difficult to treat by the simple application of
      direct clipping, endovascular coiling, or trapping. Multimodality procedures can
      be tailored to treat such aneurysms.

PMID- 15849458
TI  - Carotid rete mirabile associated with subarachnoid hemorrhage.
AB  - A 47-year-old man presented with carotid rete mirabile manifesting as
      subarachnoid hemorrhage (SAH). Computed tomography showed SAH, and angiography
      disclosed an abnormal vascular network around the petrous and cavernous portions
      of the internal carotid artery. Single photon emission computed tomography
      (SPECT) with technetium-99m methyl cysteinate dimer revealed reduced regional
      cerebral blood flow (CBF). Twelve months later, he was leading a normal life
      without neurological problems, hemorrhage, or ischemic manifestations. SPECT with
      iodine-123 N-isopropyl-p-iodoamphetamine and the acetazolamide challenge test
      showed the CBF had normalized.

PMID- 15849459
TI  - Skull metastasis from thyroid follicular carcinoma with difficult diagnosis of
      the primary lesion.
AB  - A 57-year-old male patient presented with an immobile ellipsoid mass of 6-cm
      diameter in the right occipitoparietal region. Cranial computed tomography showed
      the mass with dense contrast enhancement causing bone destruction. After
      embolization of the mass, total resection was performed. Histological examination
      showed the mass had a capsule, with no invasion of the dura mater or dermis, and
      the follicles of various sizes covered with mono-lined thyrocytes were full of
      colloid. Immunohistochemical examination showed positive staining for
      thyroglobulin. Postoperatively, levels of thyroid hormones were normal, and
      thyroid ultrasonography and technetium-99m scintigraphy showed no abnormalities.
      Fine needle aspiration biopsy performed at various locations of the thyroid gland
      revealed no atypical thyroid cells. Whole body technetium-99m scintigraphy found
      no abnormal bone involvement. The histological evidence was suggestive of
      follicular carcinoma metastasis. Surgical treatment was planned for the thyroid
      gland, but the patient did not consent. Two years later, the patient presented
      with the pain and sensitivity in the sacrum, the right iliac wing, and the right
      caput femoris. Computed tomography revealed lytic lesions in these areas. Bone
      metastases were identified. Whole body scintigraphy showed increased activity in
      these regions, but the cranium and all other tissues were normal. The patient
      underwent total thyroidectomy under a diagnosis of follicular carcinoma. The
      present case of a lytic skull lesion associated with normal thyroid tissue on
      admission but finally treated as follicular thyroid cancer emphasizes the
      difficulty in histological discrimination of follicular carcinoma from normal
      thyroid tissue.

PMID- 15849460
TI  - Sponge-induced granuloma ("gauzoma") as a complication of posterior lumbar
      surgery.
AB  - A 45-year-old woman presented with complaints of low back pain and sciatica on
      the left persisting for 2 years. She had undergone left hemilaminectomy and
      discectomy for L4-5 intervertebral disc herniation at another medical center.
      Spinal computed tomography and magnetic resonance (MR) imaging revealed a mass
      lesion in the posterior paravertebral region. The mass was hypointense with ring
      enhancement on the T(1)-weighted images and hyperintense on the T(2)-weighted
      images. Surgery found a retained sponge within the paraspinal mass cavity which
      was removed totally. Foreign-body granuloma ("gauzoma") induced by forgotten
      sponge material is not an unusual complication of posterior lumbar surgery and
      should be considered as a potential cause in cases of surgical wound infections.
      MR imaging is essential to achieve the correct differential diagnosis.

PMID- 15849461
TI  - Ligamentum flavum hematoma in the lumbar spine.
AB  - A previously healthy 45-year-old woman presented with ligamentum flavum hematoma
      manifesting as radicular leg pain. Neurological examination findings were
      consistent with L-5 root compression. An old hematoma inside the degenerated
      ligamentum flavum was drained. The cyst showed no connection to the facet joint.
      Complete resection of the mass was performed, resulting in excellent pain relief.
      The most common cystic lesion in the lumbar spine is synovial cyst associated
      with the facet joints, but ligamentum flavum hematoma should be included in the
      differential diagnosis. The preoperative diagnosis can be based on computed
      tomography and magnetic resonance imaging findings of degenerative thickening of
      the ligamentum flavum associated with a fluid component.

PMID- 15849462
TI  - Multiple epidermoid cysts located in the pineal and extracranial regions treated
      by neuroendoscopy.
AB  - A 22-year-old woman presented with a rare case of multiple epidermoid cysts
      located in the pineal and extracranial regions. Magnetic resonance (MR) imaging
      showed a lesion in the pineal region as hypointense on the T(1)-weighted image
      and hyperintense on the T(2)-weighted image, without enhancement. Neuroendoscopic
      treatment was performed under a diagnosis of pineal cyst. However, the cyst wall
      was too thick to perforate, although third ventriculostomy was performed.
      Diffusion-weighted MR imaging demonstrated the lesions in the pineal and
      extracranial regions as marked hyperintensity. The diagnosis was epidermoid cyst.
      Subsequently, neuroendoscopic treatment of the pineal epidermoid cyst was
      performed. Careful preoperative diagnosis of epidermoid cysts based on diffusion
      weighted MR imaging is required.

PMID- 15849463
TI  - Feasibility of hepatocyte transplantation-based therapies for primary
      hyperoxalurias.
AB  - Primary hyperoxalurias (PHs) are diseases caused by overproduction of oxalate by
      hepatocytes. Most patients with PHs develop nephrocalcinosis and renal failure.
      Combined liver-kidney transplantation is often used as a definitive treatment of
      PHs, but because of a large body oxalate load at the time of transplantation, the
      procedure is not always successful. Because all hepatocytes overproduce oxalate,
      partial liver replacement procedures, such as auxiliary transplantation of a
      liver lobe or hepatocyte transplantation are not expected to be useful in this
      disorder. In this paper we describe novel techniques, based on preparative
      hepatic irradiation and stimulation of hepatocyte mitosis, through loss of liver
      mass or administration of hepatic growth factor, which permit transplanted wild
      type hepatocytes to massively repopulate the liver, replacing up to 90% of the
      hepatocytes in recipient mouse livers. Application of this procedure in a
      recently developed Agxt-gene-deleted mouse model of PH1 resulted in marked
      amelioration of hyperoxaluria. We propose that further refinement of the
      different components of this procedure may permit early cell-based therapies of
      PHs, thereby preventing renal failure and its complications.

PMID- 15849464
TI  - Mitochondrial hydroxyproline metabolism: implications for primary hyperoxaluria.
AB  - BACKGROUND/AIMS: Primary hyperoxaluria results from an alteration in enzymes that
      metabolize glyoxylate. The metabolism that leads to glyoxylate synthesis is not
      well defined. The aim of this study was to investigate the production of
      glyoxylate in liver mitochondria when they metabolize hydroxyproline. METHODS:
      Mitochondria were isolated from mouse liver using Percoll gradient
      centrifugation. The metabolism of hydroxyproline was examined by a combination of
      HPLC and ion chromatography/mass spectrometry techniques. RESULTS: Glyoxylate
      production was substantially greater when mitochondria were incubated with
      hydroxyproline in comparison with proline. Inclusion of malate and glutamate with
      hydroxyproline resulted in a drop in glyoxylate and an increase in glycolate in
      the incubation mixture. This suggests an increased NAD(P)+ reduction which
      occurred with the inclusion of glutamate/malate and that the NAD(P)H production
      was required to stimulate the glyoxylate reductase-catalyzed conversion of
      glyoxylate to glycolate. The presence of glyoxylate reductase in these
      mitochondria was confirmed by measuring enzymatic activity and by Western
      blotting. CONCLUSION: These results indicate that studies on isolated
      mitochondria have the potential to help unravel the metabolism associated with
      glyoxylate and oxalate production and understand the metabolic function of
      glyoxylate reductase.

PMID- 15849465
TI  - Cellular transfection to deliver alanine-glyoxylate aminotransferase to
      hepatocytes: a rational gene therapy for primary hyperoxaluria-1 (PH-1).
AB  - BACKGROUND: Primary hyperoxaluria-type 1 (PH-1) is a rare autosomal recessive
      disorder of glyoxalate metabolism caused by deficiency in the liver-specific
      peroxisomal enzyme alanine-glyoxalate transaminase 1 (AGT) resulting in the
      increased oxidation of glyoxalate to oxalate. Accumulation of oxalate in the
      kidney and other soft tissues results in loss of renal function and significant
      morbidity. The present treatment options offer some relief in the short term, but
      they are not completely successful. In the present study, we tested the
      feasibility of corrective gene therapy for this metabolic disorder. METHODS: A
      cDNA library was made from HepG2 cells. PCR primers were designed for the AGT
      sequence with modifications to preclude mistargeting during gene delivery.
      Amplified AGT cDNA was cloned as a fusion protein with green fluorescent protein
      (GFP) using the vector EGFP-C1 (Clontech) for monitoring subcellular
      distribution. Sequence and expression of the fusion protein was verified. Fusion
      protein vectors were transfected into hepatocytes by liposomal transfection. AGT
      expression and subcellular distribution was monitored by GFP fluorescence.
      RESULTS: HepG2 cells express full-length mRNA coding for AGT as confirmed by
      insert size as well as sequence determination. Selective primers allowed us to
      generate a modified recombinant GFP-AGT fusion protein. Cellular transfections
      with Lipofectamine resulted in transfection efficiencies of 60-90%. The
      recombinant AGT did localize to peroxisomes as monitored by GFP fluorescence.
      CONCLUSIONS: The results demonstrate preliminary in vitro feasibility data for
      AGT transfection into the hepatocytes. To the best of our knowledge, this is the
      first study to attempt recombinant AGT gene therapy for treatment of primary
      hyperoxaluria-1.

PMID- 15849466
TI  - Implications of genotype and enzyme phenotype in pyridoxine response of patients
      with type I primary hyperoxaluria.
AB  - BACKGROUND: Marked hyperoxaluria due to liver-specific deficiency of
      alanine:glyoxylate aminotransferase activity (AGT) characterizes type I primary
      hyperoxaluria (PHI). Approximately half of PHI patients experience improvement in
      the degree of hyperoxaluria following pyridoxine (VB6) treatment. Recently, we
      showed an association between VB6 response and the commonest PHI mutation G170R,
      with patients possessing one or two copies showing 50% reduction or complete to
      near complete normalization of oxaluria, respectively. Two patients showed
      responses varying from this pattern. To further clarify the molecular basis of
      VB6 response in PHI, we performed additional genotyping. METHODS: 23 PHI patients
      diagnosed via hepatic enzyme analysis, hyperoxaluria and hyperglycolic aciduria
      or homozygosity for a known mutation, availability of pre- and post-VB6 24-hour
      urine oxalate and GFR >40 ml/min/1.73 m2 were included. Data was retrieved
      retrospectively, oxalate measured by oxalate oxidase, and genotyping performed by
      PCR-based methods. RESULTS: VB6 response was associated with the G170R and F152I
      mutations. Eight new sequence changes were detected. CONCLUSIONS: In PHI, two
      mutations resulting in AGT mistargeting are associated with VB6 response. Whether
      this favorable effect is specific to the peroxisomal-to-mitochondrial
      mistargeting caused by these changes or due to another mechanism remains to be
      determined.

PMID- 15849467
TI  - Serum CA19-9 measurement increases the effectiveness of staging laparoscopy in
      patients with suspected pancreatic malignancy.
AB  - BACKGROUND/AIMS: Staging laparoscopy for suspected pancreatic neoplasia is not
      widely accepted due to its low yield. The aim of this study was to determine if
      serum carbohydrate antigen (CA19-9) levels could be used to improve the selection
      of patients for staging laparoscopy. METHODS: The data from a prospectively
      collected database (1997-2004) with 159 patients who had computed tomography
      predicted resectable disease and who had undergone laparoscopic staging were
      analysed to determine if a low preoperative CA19-9 level (< or =150 kU/l, or < or
      =300 kU/l with a bilirubin >35 micromol/l) identified patients in whom
      laparoscopy was not useful. RESULTS: The CA19-9 level was >150 kU/l in 96
      patients of whom 75 (78%) were considered resectable following laparoscopic
      assessment. There were 63 patients with a CA19-9 < or =150 kU/l of whom 60 (95%)
      were considered resectable following laparoscopic assessment. The sensitivity,
      specificity, positive predictive value and negative predictive value for CA19-9 <
      or =150 kU/l in predicting that laparoscopic assessment would judge patients as
      resectable were 44, 88, 95 and 22%, respectively. A cut-off level of < or =300
      kU/l in patients with a bilirubin >35 micromol/l produced values of 30, 94, 94
      and 28%, respectively. By using CA19-9 < or =150 kU/l, laparoscopy could have
      been avoided in 40% of patients, increased to 55% of patients with adjustment for
      the presence of jaundice; concomitantly, the yield from laparoscopy would have
      been increased from 15 to 22 and 25%, respectively. CONCLUSION: Use of serum CA19
      9 levels would increase the efficiency of laparoscopic staging in patients with
      suspected pancreatic malignancy.

PMID- 15849468
TI  - The place of the posterior surgical approach for lesions of the rectum.
AB  - BACKGROUND: Although there are many advantages of a posterior approach to rectal
      disease, these procedures are not widely accepted because many surgeons fear the
      postoperative complications. METHODS: The medical records were reviewed of 57
      patients who underwent a posterior approach to the rectum between January 1980
      and December 2002. RESULTS: Twenty-eight men and 29 women with a mean age of 70.5
      (range 47-83) years underwent either a posterior transsacral (n = 52) or a
      transsphincteric (n = 5) procedure. Indications for surgery were benign lesions
      (n = 33), e.g. villous adenoma, rectal prolapse and endometriosis as well as
      invasive adenocarcinoma (n = 24). All patients with an invasive adenocarcinoma
      were classified as ASA grade III or IV. Postoperative morbidity occurred in 12
      patients (21%), consisting of temporary incontinence, anastomotic leakage, wound
      infection, and hemorrhage. There was no mortality. During a mean follow-up of 29
      (range 2-86) months, 3 patients with a villous adenoma and 2 patients who were
      treated for a malignant lesion had a locally recurrent lesion. CONCLUSION: We
      believe that a posterior approach to the rectum should be considered for various
      benign and selected malignant diseases, especially in case of elderly patients or
      patients with a compromised general condition, and has to be a part of the
      surgeon's armamentarium.

PMID- 15849469
TI  - Treatment of fistulas in ano with fibrin glue.
AB  - BACKGROUND: Recent publications show promising results using fibrin glue in the
      treatment of anal fistulas. The technique is simple, repeatable, with minor
      surgical trauma so that sphincter function is preserved and further treatment
      options are not compromised. The aim of this pilot study was to analyse if we
      could reproduce the results reported in the literature, using this simple
      technique. METHODS: Patients with a primary or recurrent anal fistula were
      included in this trial. Patients with a complex fistula were excluded. Under
      general or spinal anaesthesia, the fistulas were curetted and injected with
      fibrin glue. Follow-up visits were scheduled for 1 week, 6 weeks and 6 months.
      RESULTS: Twenty-seven patients were included. The overall success rate was 33%
      after a mean follow-up of 27 weeks. Patients with a recurrent fistula had a
      poorer outcome (success rate 14%). None of the patients suffered from
      postoperative continence problems, and no other complications were recorded.
      CONCLUSION: This study confirms the safety of fibrin glue in the treatment of
      anal fistulas. However, a high success rate could not be reproduced.

PMID- 15849470
TI  - Urgent laparoscopic cholecystectomy is the best management for biliary colic. A
      prospective randomized study of 75 cases.
AB  - BACKGROUND/AIM: Delay of laparoscopic cholecystectomy after the diagnosis of
      biliary colic may increase the probability of recurrent emergency admission while
      awaiting elective cholecystectomy. The aim of this study was to compare the
      possible advantages and safety of urgent laparoscopic cholecystectomy (ULC) with
      elective laparoscopic cholecystectomy (ELC) in patients with biliary colic.
      PATIENTS AND METHODS: Between 2001 and 2003, 75 patients with biliary colic were
      included in this study. The patients were classified into following two groups:
      patients who had ULC in 24 h were in group I (n = 28) and patients who had ELC
      (mean interval 4.22 +/- 1.42 months) were in group II (n = 35). Conversion to
      open cholecystectomy, operative time, postoperative hospital stay, costs, and
      complications were evaluated. RESULTS: In group II, 9 patients made a total of 13
      return visits to the emergency department with recurrent attacks of biliary colic
      or complications of gallstone disease. Mean operative time increased from 35.1 +/
      6.74 min for urgent laparascopic cholecystectomy to 49.9 +/- 6.12 min for ELC (p
      > 0.05) and hospital stay time increased from 1.06 +/- 0.4 to 2.31 +/- 2.36 days
      (p < 0.05). Conversion to open cholecystectomy increased from 0% in group I to
      17.2% in group II (p < 0.05). DISCUSSION: ULC for biliary colic may be the most
      medically efficacious and cost-effective treatment.

PMID- 15849471
TI  - Prognostic factors of perforated sigmoid diverticulitis in the elderly.
AB  - BACKGROUND: The Finnish population is aging fast and the prevalence of perforated
      sigmoid diverticulitis is simultaneously increasing in northern Finland. The fact
      that an increasing number of elderly patients, with their age-specific problems,
      are subjected to emergency surgery for acute diverticulitis underlines the
      importance of risk stratification. METHODS: One hundred and seventy-two patients
      admitted to Oulu University Hospital because of diverticular perforation from
      1983 to 2002 were identified from the computer database. The clinical variables
      were evaluated as prognostic indicators of postoperative complications, mortality
      and time of hospitalization. RESULTS: The resection rate was 91%; 64 primary
      anastomoses, 93 Hartmann's procedures and two covering colostomies were
      performed. The overall complication rate was 33%. In patients under 70 years, a
      stepwise logistic regression analysis showed that the Mannheim Peritonitis Index
      (MPI) score and American Society of Anesthesiologists (ASA) score were
      independent prognostic factors. None of factors predicted morbidity in patients
      over 70 years. Overall mortality rate was 8%, without any significant difference
      between the procedures. Of the clinical variables, MPI score, ASA score, Hinchey
      classes and malnutrition correlated with mortality. All patients who died
      presented with ASA scores of III-IV, and 12 out of 14 patients had an MPI score
      of II. In a stepwise logistic regression analysis, only the MPI score seemed to
      be an independent predictor of mortality. CONCLUSIONS: Mortality is related to
      age but age alone is not an independent predictor of mortality. The MPI score is
      useful in predicting the risk of death in patients with perforated
      diverticulitis.

PMID- 15849472
TI  - Esophageal adenocarcinomas in heterotopic gastric mucosa: review and report of a
      case with complete response to neoadjuvant radiochemotherapy.
AB  - Adenocarcinomas are exceedingly rare in the cervical esophagus (26 reported
      cases), where squamous cell cancer (SCC) is the predominant tumor type.
      Esophageal heterotopic gastric mucosa (HGM) - a frequent remnant of incomplete
      replacement of the original columnar epithelium during the embryonic period - is
      suspected as cellular origin of cervical esophageal adenocarcinomas. As in any
      rare tumor entity, no standard treatment strategy is available for cervical
      esophageal adenocarcinomas. We herein report about the case of a 52-year-old man
      with a locally advanced, irresectable cervical esophageal adenocarcinoma
      originating in HGM. We decided on a neoadjuvant therapy (48.6 Gy + 5
      FU/cisplatin) derived from experiences with SCC. Restaging showed an
      extraordinary good clinical response of the previously irresectable tumor.
      Subsequently the patient underwent limited cervical esophageal resection,
      lymphadenectomy and interposition of a free jejunal loop for reconstruction.
      Postoperative histopathological work-up of the specimen showed no residual tumor
      tissue, but unchanged HGM. This is the first case with complete response of a
      rare cervical esophageal adenocarcinoma to a neoadjuvant protocol. On 3-year
      follow-up the patient is doing fine with no complaints of dysphagia and no
      evidence of local or systemic recurrence.

PMID- 15849473
TI  - Ribavirin treatment in patients with chronic hepatitis C infection who had renal
      transplantation.

PMID- 15849474
TI  - A calcitonin-secreting tumor of the pancreas.

PMID- 15849475
TI  - c-Myc antisense oligonucleotides preserve smooth muscle differentiation and
      reduce negative remodelling following rat carotid arteriotomy.
AB  - OBJECTIVES: The vascular biology of restenosis is complex and not fully
      understood, thus explaining the lack of effective therapy for its prevention in
      clinical settings. The role of c-Myc in arteriotomy-induced stenosis, smooth
      muscle cell (SMC) differentiation and apoptosis was investigated in rat carotids
      applying full phosphorothioate antisense (AS) oligonucleotides (ODNs). METHODS:
      Carotid arteries from WKY rats were submitted to arteriotomy and to local
      application of ODNs through pluronic gel. Apoptosis (deoxynucleotidyl transferase
      mediated dUTP nick end-labelling), SMC differentiation (SM22 immunofluorescence)
      and vessel morphology and morphometry (image analysis) were determined 2, 5 and
      30 days after injury, respectively. RESULTS: AS ODNs induced a 60% decrease of
      target c-Myc mRNA 4 h after surgery in comparison to control sense (S) and
      scrambled ODN-treated carotids (p < 0.05). A significant 37 and 50% decrease in
      SM22 protein in the media of S ODN-treated and untreated carotids was detected
      when compared to uninjured contralateral arteries (p < 0.05). This reduction in
      SM22 expression was prevented in AS ODN-treated carotids. Stenosis was mainly due
      to adventitial constrictive remodelling. Lumen area in AS ODN-treated carotids
      was 35% greater than in control arteries 30 days after surgery (p < 0.05). TUNEL
      assay revealed increased apoptosis in AS ODN-treated carotids (p < 0.05).
      CONCLUSIONS: c-Myc AS ODNs reduce arteriotomy-induced negative remodelling. This
      is accompanied by maintained SMC differentiation and greater apoptosis. The
      combination of reduced c-Myc-induced proliferation and increased apoptosis may
      thus underlie the less severe remodelling upon treatment with c-Myc mRNA AS ODN.

PMID- 15849476
TI  - Intraperitoneal heparin ameliorates the systemic inflammatory response in PD
      patients.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) suffer from high
      mortality rates of cardiovascular diseases, conditions closely linked to the
      magnitude of their chronic low-grade inflammation. As heparins have been
      suggested to possess anti-inflammatory properties, we set out to investigate the
      impact of long-term treatment with intraperitoneal heparin on local and systemic
      inflammation in peritoneal dialysis (PD) patients. METHODS: In a double-blinded
      cross-over study, 21 PD patients with ESRD were randomised to inject either 4,500
      anti-Xa IU tinzaparin or placebo (isotonic saline) into their morning dialysis
      bags every day for two periods of 3 months separated by a 1-month wash-out
      period. Blood and dialysate samples were analysed for inflammatory markers at the
      start and end of each treatment period. In dialysate, the appearance rates of the
      inflammatory markers were calculated to adjust for ultrafiltration variations.
      RESULTS: Eleven patients completed the trial. Treatment with intraperitoneal
      tinzaparin was accompanied with a median 25.8% reduction of the plasma C-reactive
      protein concentration (p = 0.032), a 7.3% reduction of the plasma fibrinogen
      concentration (p = 0.042) and a 54.5% reduction of the dialysate interleukin 6
      appearance rate (p = 0.007) compared with placebo. CONCLUSION: Long-term
      treatment with intraperitoneal tinzaparin of ESRD patients on PD reduces local
      and systemic concentrations of inflammatory markers.

PMID- 15849477
TI  - Baseline oxysterols and other markers of oxidative stress, inflammation and
      malnutrition in the vitamin e and intima media thickness progression in end-stage
      renal disease (VIPER) cohort.
AB  - BACKGROUND AND OBJECTIVES: Oxysterols are markers of oxidative stress, levels of
      which have not yet been reported in hemodialysis (HD) patients. This study was
      designed to compare levels of the oxysterols 7-ketocholesterol (7KC) and 7beta
      hydroxycholesterol (7betaOH) between a cohort of HD patients and healthy
      controls. METHODS: This nested cross-sectional study reflects baseline (pre
      intervention) values for markers of oxidative stress, inflammation and nutrition
      status in the 160-member vitamin E and carotid intima media thickness progression
      in end-stage renal disease (VIPER) cohort (age 64.1 +/- 8.8, 33.5% female). Age-
      and sex-matched healthy volunteers served as controls. Plasma oxysterols 7KC and
      7betaOH were determined by isotope dilution gas chromatography/mass spectrometry.
      RESULTS: Despite higher plasma alpha-tocopherol levels in HD patients than
      controls (36.0 +/- 9.3 vs. 31.8 +/- 8.4 micromol/l, p = 0.007), 7KC levels (9.8
      +/- 6.9 vs. 5.9 +/- 2.8 nmol/mmol cholesterol, p < 0.0001) and 7betaOH levels
      (8.7 +/- 4.3 vs. 2.7 +/- 1.6 nmol/mmol cholesterol, p < 0.0001) were higher in HD
      patients. The oxysterol 7betaOH was significantly, inversely associated with
      prealbumin (r = -0.18, p = 0.03), though neither oxysterol was significantly
      associated with any other marker of oxidative stress, inflammation or nutrition
      status and did not discriminate for CVD in HD patients. CONCLUSIONS: Elevated
      levels of the oxysterols 7KC and 7betaOH indicate that HD patients are in a state
      of oxidative stress compared to healthy controls. However, oxysterols 7KC and
      7betaOH did not appear to contribute additional information about oxidative
      stress among HD patients.

PMID- 15849478
TI  - Bezafibrates cause moderate, reversible impairment in renal function in patients
      without prior renal disease.
AB  - BACKGROUND/AIMS: To determine whether bezafibrates have adverse effects on renal
      function. METHODS: (1) A 3-year retrospective survey of 526 patients who were on
      bezafibrate for a while and 614 controls following fluctuations of serum
      creatinine levels. (2) A prospective study on 33 patients with previous evidence
      of bezafibrate-induced elevation in serum creatinine. The patients were examined
      after 3 months on bezafibrate 400 mg/day and then after 3 months without
      bezafibrate. Eight patients repeated the tests after 3 months on bezafibrate 200
      mg/day. RESULTS: Retrospective: 295 bezafibrate-treated patients (56%) and 67
      controls (11%) demonstrated fluctuations > or = 0.2 mg/dl in serum creatinine
      levels (p < 0.001); 113 patients (21%) and 16 controls (3%) showed fluctuations >
      or = 0.3 mg/dl (p < 0.001). Prospective: bezafibrate 400 mg/dl increased serum
      creatinine from 1.16 +/- 0.19 to 1.42 +/- 0.2 mg/dl (p < 0.001) and urea from 37
      +/- 8 to 44 +/- 8 mg/dl (p < 0.001); creatinine clearance (Ccr) decreased from
      104 +/- 23 to 82 +/- 27 ml/min (p < 0.001). CPK increased from 82 +/- 32 to 130
      +/-58 mg/dl (p < 0.0001) and urinary myoglobin increased from 95.4 +/- 21 to 199
      +/- 99 mg/dl (p < 0.0001). The 8 patients given bezafibrate 200 mg/dl experienced
      similar dose-dependent changes. CONCLUSIONS: Bezafibrate causes quiet common,
      dose-dependent and reversible changes in serum creatinine in patients with normal
      renal function, associated with a significant increase in serum CPK and urine
      myoglobin, suggestive of drug-induced mild subclinical skeletal muscle injury
      compromising renal function.

PMID- 15849479
TI  - Large-scale albuminuria screen for nephropathy models in chemically induced mouse
      mutants.
AB  - BACKGROUND/AIM: Phenotype-driven screening of a great pool of randomly mutant
      mice and subsequent selection of animals showing symptoms equivalent to human
      kidney diseases may result in the generation of novel suitable models for the
      study of the pathomechanisms and the identification of genes involved in kidney
      dysfunction. METHODS: We carried out a large-scale analysis of ethylnitrosourea
      (ENU)-induced mouse mutants for albuminuria by using qualitative SDS
      polyacrylamide gel electrophoresis. RESULTS: The primary albuminuria screen
      preceded the comprehensive phenotypic mutation analysis in a part of the mice of
      the Munich ENU project to avoid loss of mutant animals as a consequence of
      prolonged suffering from severe nephropathy. The primary screen detected six
      confirmed phenotypic variants in 2,011 G1 animals screened for dominant mutations
      and no variant in 48 G3 pedigrees screened for recessive mutations. Further
      breeding experiments resulted in two lines showing a low phenotypic penetrance of
      albuminuria. The secondary albuminuria screen was carried out in mutant lines
      which were established in the Munich ENU project without preceding primary
      albuminuria analysis. Two lines showing increased plasma urea levels were chosen
      to clarify if severe kidney lesions are involved in the abnormal phenotype. This
      analysis revealed severe albuminuria in mice which are affected by a recessive
      mutation leading to increased plasma urea and cholesterol levels. CONCLUSION:
      Thus, the phenotypic selection of ENU-induced mutants according to the parameter
      proteinuria in principle demonstrates the feasibility to identify nephropathy
      phenotypes in ENU-mutagenized mice.

PMID- 15849480
TI  - Cyclooxygenase-2 inhibitor decreases extracellular matrix synthesis in stretched
      renal fibroblasts.
AB  - BACKGROUND/AIMS: Both TGF-beta and cyclooxygenase-2 have been implicated in the
      pathogenesis of interstitial fibrosis in unilateral ureteral obstruction (UUO).
      Cyclic tensile stretch has been used in vitro to mimic the changes in intrarenal
      pressure in UUO. We sought to determine the effect of meloxicam (a selective
      cyclooxygenase-2 inhibitor) on extracellular matrix and TGF-beta synthesis in
      stretched renal fibroblasts (NRK-49F). METHODS: NRK-49F cells were subject to
      cyclic stretch (6 cycles/min, 15% elongation) using a Flexcell apparatus. Cells
      were stretched in the absence or presence of meloxicam for 48 h, and then cells
      and supernatants were isolated. Collagen was quantified by the Sircol assay;
      fibronectin and laminin were visualized using immunofluorescence. TGF-beta was
      quantified by ELISA, and protease activity determined by a colorimetric assay.
      RESULTS: Both collagen and TGF-beta synthesis were increased following a 48-hour
      stretch of NRK-49F. Meloxicam significantly decreased the collagen and TGF-beta
      response to stretch. Stretch-induced fibronectin and laminin synthesis was also
      decreased by meloxicam. NRK-49F protease activity was decreased by stretch; this
      was unaffected by meloxicam. CONCLUSIONS: Stretch of NRK-49F results in
      extracellular matrix synthesis, a process which may be activated in UUO and
      contribute to interstitial fibrosis. Inhibition of cyclooxygenase-2 may reduce
      fibrosis through a TGF-beta-dependent process.

PMID- 15849481
TI  - Designing future clinical trials in acute pancreatitis.

PMID- 15849482
TI  - 'Understanding the development of pancreatic cancer will emerge from basic
      research'. An interview with Prof. Hans G. Beger. Interviewed by Martin E.
      Fernandez-Zapico.
AB  - Prof. Hans Beger is a worldwide-recognized pancreatologist in the treatment of
      pancreatic diseases. He led the way in pancreatic surgery with the development of
      a classic intervention: the Beger procedure for the treatment of chronic
      pancreatitis. In this interview for Pancreatology Prof. Beger shares his life
      experiences as a scientist in pancreatic research.

PMID- 15849483
TI  - Endocrine pancreatic insufficiency in chronic pancreatitis.
AB  - Chronic pancreatitis (CP) is considered to be a rare cause of diabetes mellitus.
      However, in both the developed and developing world, there is an increasing
      number of patients suffering from pancreatitis probably due to lifestyle changes,
      which is partially associated with both social factors and the poor health status
      of immigrants. Owing to these circumstances, CP has evolved with one of the
      possible causes of diabetes in a selected group of patients and should be
      included in the differential diagnosis of diabetes. Several studies have shown
      that the long-term rate of diabetic complications in patients with CP and insulin
      dependent diabetes is similar to that in patients with type 1 diabetes of equal
      duration. The hypothesis that early diagnosis of CP should result in better
      prognosis is not validated and may complicate the issue, since the risk of
      diabetes has been shown to increase significantly only once pancreatic
      calcification has developed. Accumulative evidence suggests that the risk of
      diabetes is not influenced by elective pancreatic surgical procedures other than
      distal pancreatectomy. The lack of contemporary data points to the urgent need
      for large prospective studies in order to accurately evaluate the special
      characteristics of disorders in glucose homeostasis in patients with CP.

PMID- 15849484
TI  - Pathophysiology of acute pancreatitis.
AB  - Acute pancreatitis is a common clinical condition. It is a disease of variable
      severity in which some patients experience mild, self-limited attacks while
      others manifest a severe, highly morbid, and frequently lethal attack. The exact
      mechanisms by which diverse etiological factors induce an attack are still
      unclear. It is generally believed that the earliest events in acute pancreatitis
      occur within acinar cells. Acinar cell injury early in acute pancreatitis leads
      to a local inflammatory reaction. If this inflammatory reaction is marked, it
      leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS
      leads to distant organ damage and multiple organ dysfunction syndrome (MODS).
      MODS associated with acute pancreatitis is the primary cause of morbidity and
      mortality in this condition. Recent studies have established the role played by
      inflammatory mediators in the pathogenesis of acute pancreatitis and the
      resultant MODS. At the same time, recent research has demonstrated the importance
      of acinar cell death in the form of apoptosis and necrosis as a determinant of
      pancreatitis severity. In this review, we will discuss about our current
      understanding of the pathophysiology of acute pancreatitis.

PMID- 15849485
TI  - Severe acute pancreatitis: case-oriented discussion of interdisciplinary
      management.
AB  - The clinical course of an episode of acute pancreatitis varies from a mild,
      transitory illness to a severe often necrotizing form with distant organ failure
      and a mortality rate of 20-40%. Patients with severe pancreatitis, representing
      about 15-20% of all patients with acute pancreatitis, need to be identified as
      early as possible after onset of symptoms allowing starting intensive care
      treatment early in the disease process. An episode of severe acute pancreatitis
      progresses in two phases. The first 10-14 days are characterized by a systemic
      inflammatory response syndrome maintained by the release of various inflammatory
      mediators. The second phase, beginning about 10-14 days after the onset of the
      disease is dominated by sepsis-related morbidity due to infected peripancreatic
      and pancreatic necrosis. This state is associated with septic multiple organ
      systemic failure. The importance of infection on the outcome of necrotizing
      pancreatitis has been clearly delineated and the pre-emptive use of broad
      spectrum antibiotics that achieve effective tissue concentrations is considered
      standard management of patients with severe necrotizing pancreatitis, especially
      if associated with organ failure or extended necrosis. Patients with infected
      necrosis should undergo a surgical intervention. The standard open technique
      consisting of an organ preserving necrosectomy followed by a postoperative
      concept of lavage and/or drainage to evacuate necrotic debris occurring during
      the further course has recently been challenged by various minimally invasive
      approaches.

PMID- 15849486
TI  - Early sequential changes in serum markers of acute pancreatitis induced by
      endoscopic retrograde cholangiopancreatography.
AB  - BACKGROUND/AIMS: Trypsinogen activation is thought to play a crucial role in the
      pathogenesis of acute pancreatitis (AP). Our aim was to characterize the very
      early sequential changes of trypsinogen-1, trypsinogen-2, the trypsin-2-alpha1
      antitrypsin complex (T2-AAT), and pancreatic secretory trypsin inhibitor (PSTI)
      in serum from patients with pancreatitis induced by endoscopic retrograde
      cholangiopancreatography (ERCP), a model for studying the early phase of the
      disease in humans. PATIENTS AND METHODS: The study population consisted of 659
      consecutive patients with 897 ERCP procedures. Blood samples were obtained before
      and at different time points after the procedure. The serum concentrations of
      trypsinogen-1 and trypsinogen-2, PSTI and T2-AAT were determined by time-resolved
      immunofluorometric assays. RESULTS: ERCP-induced pancreatitis developed after 50
      of the 897 ERCP procedures (5.6%). Sixty-one randomly selected ERCP patients
      without post-ERCP pancreatitis served as controls. Trypsinogen-1 and trypsinogen
      2 showed an equally steep increase during the two first hours after ERCP in
      patients developing AP, but trypsinogen-1 decreased more rapidly than trypsinogen
      2, which remained elevated during the 5-day study period. Serum PSTI also
      increased rapidly whereas T2-AAT increased more slowly peaking at 24 h. In
      patients developing post-ERCP pancreatitis the median concentration of
      trypsinogen-1 was markedly higher than in the controls already before the ERCP
      procedure. In the control group the concentrations of trypsinogen-1, trypsinogen
      2, PSTI and T2-AAT did not change significantly. CONCLUSIONS: The rapid increase
      of trypsinogen-1 and trypsinogen-2 and PSTI in the early phase of AP suggests
      that release of pancreatic enzymes is the initial event while the delayed
      increase of T2-AAT may reflect that the capacity of the intrapancreatic PSTI
      based inhibitory mechanism has been exhausted.

PMID- 15849487
TI  - Novel antioxidant ameliorates the fibrosis and inflammation of cerulein-induced
      chronic pancreatitis in a mouse model.
AB  - BACKGROUND/AIM: Oxygen free radicals (OFRs) mediate an important step in the
      initiation of experimental acute pancreatitis and several clinical findings
      suggested the possible contribution of OFRs to the pathogenesis of pancreatic
      fibrosis. So far, there are no studies which reporting potential role of OFRs in
      development of chronic pancreatitis with the prevention with antioxidants. This
      study was aimed to establish the mice model of chronic fibrosing pancreatitis and
      to prove the involvement of OFRs in chronic pancreatitis with fibrosis. METHODS:
      Repeated intraperitoneal cerulein injection was performed to induce chronic
      pancreatitis in mice. Histological changes in the pancreas were examined, and
      markers for oxidative stress were measured in the pancreatic tissue and serum of
      the mice. DA-9601, a phytochemical possessing anti-inflammatory and antioxidative
      action, was given together with cerulein to the mice. RESULTS: Repeated
      intraperitoneal injection of cerulein provoked significant severity of chronic
      fibrosing pancreatitis after 5 weeks. After treatment of DA-9601, the extents of
      pancreatic fibrosis were statistically significantly decreased in accordance with
      lessened pancreatic inflammations. The NF-kappaB binding activities were
      increased in chronic pancreatitis, which were significantly attenuated after DA
      9601 treatment. The levels of myeloperoxidase and iNOS activities were also
      significantly decreased in DA-9601-treated group compared to the pancreatitis
      only group. Cytoprotective proteins such as heat shock protein-70 (HSP) and
      metallothionein were significantly increased in the DA-9601-treated group. DA
      9601 decreased the expressions of alpha-SMA and type I collagen in cultured
      pancreatic stellate cells. CONCLUSIONS: Oxidative stress was principally involved
      in the pathogenesis of chronic pancreatitis with fibrosis.

PMID- 15849488
TI  - Increased central memory T cells in patients with chronic pancreatitis.
AB  - BACKGROUND/AIMS: A dysregulated immune response has been suggested to be
      important for the pathogenesis of chronic pancreatitis (CP). Formation of
      immunological memory is based on the differentiation of naive T lymphocytes to
      memory T lymphocytes after exposure to antigens and specific cytokines. The aim
      of this study was to analyze peripheral blood mononuclear cells (PBMCs) in
      patients with CP for different T lymphocyte subsets including naive and memory T
      cells. METHODS: PBMCs from 9 patients who had undergone pancreatic resection due
      to CP, 9 CP patients who had not been resected and 9 healthy controls were
      analyzed by flow cytometry. RESULTS: Patients with CP had a skewed distribution
      of T lymphocytes, with an increased level of CCR7+/CD45RA- central memory T
      lymphocytes compared to healthy controls. Nonresected CP patients and subjects
      who had undergone pancreatic resection due to CP had similar levels of central
      memory T lymphocytes. CONCLUSION: Our results indicate that the dysregulation of
      the immune system in chronic pancreatitis seems to persist even after removal of
      large parts of the local inflammatory site. We suggest that the increase of
      central memory T lymphocytes may be important for maintaining the inflammatory
      process in chronic pancreatitis.

PMID- 15849489
TI  - Comparing the urinary pancreolauryl ratio and faecal elastase-1 as indicators of
      pancreatic insufficiency in clinical practice.
AB  - BACKGROUND: The urine pancreolauryl ratio (uPLR) and, more recently, the faecal
      pancreatic elastase-1, are widely used for the noninvasive diagnosis of exocrine
      pancreatic insufficiency. Both tests have previously been validated against 'gold
      standard' tests of pancreatic function, but their use in a clinical setting has
      never been directly compared. METHODS: We performed a comparative study of the
      pancreolauryl ratio (PLR) and the faecal elastase-1 (FE-1) test in patients with
      a clinical suspicion for pancreatic insufficiency. The results were compared with
      the clinical response to pancreatic enzyme supplementation using pre-defined
      criteria. RESULTS: Forty-five patients were enrolled in the study and 33 were
      given a trial of pancreatic enzyme supplementation. Twenty-four out of these 33
      showed a positive clinical response to enzyme supplements. Of the 24 responders,
      19 had positive FE-1 (<200 microg/g faeces), but only 12 had a positive uPLR
      (<20). There was a significant correlation between the FE-1 result and clinical
      response to enzyme supplements (p = 0.01), but not between the PLR and clinical
      response (p = 0.15). CONCLUSIONS: FE-1 is a simpler test for the patient to
      perform and more accurately predicts the response to pancreatic enzyme
      supplementation in patients with chronic, unexplained diarrhoea with a clinical
      suspicion of pancreatic insufficiency than the PLR. This makes the FE-1 of
      greater use in clinical practice than the PLR.

PMID- 15849490
TI  - Osteoclast-like giant cell tumor of the pancreas associated with mucus-secreting
      adenocarcinoma. Case report and discussion of the histogenesis.
AB  - BACKGROUND/AIMS: The osteoclast-like giant cell tumor of the pancreas is a rare
      entity that closely resembles giant cell tumor of the bone, which has also been
      observed in many other organs. Some tumors also contain areas of ductal
      adenocarcinoma. Conflicting opinions exist regarding the tumor origin, whether it
      is mesenchymal or epithelial, neoplastic or reactive. METHODS: We report the case
      of a 69-year-old Brazilian man with a mass in the head of the pancreas, the
      histological examination of which revealed a predominant component of osteoclast
      like giant cells within a background of pleomorphic mononuclear cells with
      osteoid formation and other areas composed of conventional mucus-secreting
      adenocarcinoma. RESULTS: Immunohistochemistry showed that carcinoma cells of the
      usual type expressed epithelial antigens (EMA and cytokeratin) and lysozyme; the
      giant cells expressed vimentin, CD45, CD68, and lysozyme; and the mononuclear
      cells expressed macrophage marker (HAM56), vimentin, and lysozyme, and only some
      of them expressed epithelial markers, CD45, and CD68. CONCLUSION: Our
      immunohistochemical findings reveal that the giant cells in this case are of
      mesenchymal origin may be from the bone marrow cells. We believe that it is
      important to determine the histogenesis in each case to carry out the pertinent
      adjuvant therapy.

PMID- 15849491
TI  - Somatostatin-producing pancreatic endocrine carcinoma presented as relapsing
      cholangitis -- a case report.
AB  - Somatostatin-producing endocrine tumors are rare neoplasms usually arising in the
      pancreas and duodenum and they account for less than 1% of all gastrointestinal
      endocrine tumors. Besides somatostatinoma syndrome, which is characterized by
      diabetes mellitus, steatorrhea and cholelithiasis, patients with somatostatin
      producing endocrine tumors commonly complain of nonspecific symptoms such as
      vague abdominal pain, weight loss or changes in bowel habits. Tumor behavior
      cannot be predicted by histological features alone, and malignancy is determined
      by the presence of metastases. We report here a case of malignant pancreatic
      endocrine tumor producing somatostatin presented as relapsing cholangitis who was
      treated with Whipple pancreatoduodenectomy.

PMID- 15849503
TI  - Presidential address: Southern Surgical Association: surgical science in the
      Southern.

PMID- 15849504
TI  - Gastrin-releasing peptide-induced down-regulation of tumor suppressor protein
      PTEN (phosphatase and tensin homolog deleted on chromosome ten) in
      neuroblastomas.
AB  - OBJECTIVES: To evaluate whether aggressive, undifferentiated neuroblastomas
      express tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on
      chromosome ten) and to examine the effects of gastrin-releasing peptide (GRP) on
      PTEN gene and protein expression. SUMMARY BACKGROUND DATA: We have previously
      shown that neuroblastomas secrete GRP, which binds to its cell surface receptor
      (GRP-R) to stimulate cell growth in an autocrine fashion. However, the effects of
      GRP on expression of the tumor suppressor gene PTEN have not been elucidated in
      neuroblastomas. METHODS: Paraffin-embedded sections from human neuroblastomas
      were analyzed for PTEN and phospho-Akt protein expression by
      immunohistochemistry. Human neuroblastoma cell lines (SK-N-SH and SH-SY5Y) were
      stably transfected with the plasmid pEGFP-GRP-R to establish GRP-R overexpression
      cell lines, and the effects of GRP on PTEN gene and protein expression were
      determined. RESULTS: A decrease in the ratio of PTEN to phospho-Akt protein
      expression was identified in poorly differentiated neuroblastomas. An increase in
      GRP binding capacity was confirmed in GRP-R overexpressing cells, which
      demonstrated an accelerated constitutive cell growth rate. PTEN gene and protein
      expression was significantly decreased in GRP-R overexpressing cells when
      compared with controls. CONCLUSIONS: Our findings demonstrate decreased
      expression of the tumor suppressor protein PTEN in more aggressive
      undifferentiated neuroblastomas. An increase in GRP binding capacity, as a result
      of GRP-R overexpression, down-regulates PTEN expression. These findings suggest
      that an inhibition of the tumor suppressor gene PTEN may be an important
      regulatory mechanism involved in GRP-induced cell proliferation in
      neuroblastomas.

PMID- 15849505
TI  - Surgical management of hilar cholangiocarcinoma.
AB  - OBJECTIVE: To assess the surgical management of hilar cholangiocarcinoma over a
      time period when liver resection was considered standard management. SUMMARY
      BACKGROUND DATA: Hilar cholangiocarcinoma remains a difficult challenge for
      surgeons. An advance in surgical treatment is the addition of liver resection to
      the procedure. However, liver resection in the setting of liver dysfunction
      caused by biliary obstruction can be associated with increased mortality.
      METHODS: Between 1997 and 2004, 80 patients with hilar cholangiocarcinoma having
      surgery were reviewed. Fifty-three patients had attempted curative resections, 14
      patients had palliative bypasses, while 13 patients had findings that precluded
      any further intervention. Twenty-three patients required portal vein resection
      and reconstruction to achieve negative margins, 3 of which also required
      reconstruction of the hepatic artery. RESULTS: Patients undergoing resection had
      a 9% operative mortality, with morbidity of 40%. Patients who demonstrated lobar
      hypertrophy preoperatively due to tumor involvement of the contralateral liver or
      induced with portal vein embolization (PVE) had a significantly lower operative
      mortality than those patients without hypertrophy. Median overall survival in
      patients resected was 40 months, with 5-year survival of 35%. Negative margins
      were achieved in 80% of cases and were associated with improved survival. Five
      year survival in patients undergoing resection with negative margins was 45%.
      CONCLUSION: Combined liver and bile-duct resection can be performed for hilar
      cholangiocarcinoma with acceptable mortality, though higher than that for liver
      resections performed for other indications. The use of PVE in cases where
      hypertrophy of the remnant liver has not occurred preoperatively may reduce the
      risk of operative mortality.

PMID- 15849506
TI  - Papillary phenotype confers improved survival after resection of hilar
      cholangiocarcinoma.
AB  - OBJECTIVE: The current study compares outcome after resection of papillary hilar
      cholangiocarcinoma to that of the more common nodular-sclerosing subtype.
      METHODS: Clinical, radiologic, histopathologic, and survival data on all patients
      with hilar cholangiocarcinoma were analyzed. Resected tumors were reexamined and
      classified as nodular-sclerosing (no component of papillary carcinoma) or
      papillary (any component of papillary carcinoma); for papillary tumors, the
      proportion of invasive carcinoma present was determined. Differences in the
      clinical behavior and histopathologic features of nodular-sclerosing and
      papillary tumors were assessed. RESULTS: From January 1991 to November 2003, 279
      patients were evaluated, 154 men (55.2%) and 125 women (44.8%), with a mean age
      of 65.4 +/- 0.7 years (median = 68, range 23-87 years). Of the 215 patients
      explored, 106 (49.5%) underwent a complete gross resection. An en bloc partial
      hepatectomy (n = 87) and an R0 resection (n = 82) were independent predictors of
      favorable outcome. Operative mortality was 7.5% but was 2.8% over the last 4
      years of the study, and there were no operative deaths in the last 33 consecutive
      resections. Twenty-five resected tumors (23.6%) contained a papillary component:
      12 were minimally or noninvasive (<10% invasive cancer) and 13 had an invasive
      component ranging from 10% to 95% (> or =10%). Patients with papillary and
      nodular-sclerosing tumors had similar demographics, operative procedures, and
      proportion of R0 resections. By contrast, papillary tumors were significantly
      larger, more often well-differentiated, and earlier stage. Disease-specific
      survival after resection of papillary tumors (55.7 months) was greater than after
      resection of nodular-sclerosing lesions (33.5 months, P = 0.013). The papillary
      phenotype was an independent predictor of survival, although the benefit was more
      pronounced for less invasive tumors. CONCLUSIONS: The presence of a component of
      papillary carcinoma is more common than previous reports have suggested and is an
      important determinant of survival after resection of hilar cholangiocarcinoma.

PMID- 15849507
TI  - Effect of surgical margin status on survival and site of recurrence after hepatic
      resection for colorectal metastases.
AB  - OBJECTIVE: To evaluate the influence of surgical margin status on survival and
      site of recurrence in patients treated with hepatic resection for colorectal
      metastases. METHODS: Using a multicenter database, 557 patients who underwent
      hepatic resection for colorectal metastases were identified. Demographics,
      operative data, pathologic margin status, site of recurrence (margin, other
      intrahepatic site, extrahepatic), and long-term survival data were collected and
      analyzed. RESULTS: On final pathologic analysis, margin status was positive in 45
      patients, and negative by 1 to 4 mm in 129, 5 to 9 mm in 85, and > or =1 cm in
      298. At a median follow-up of 29 months, the 1-, 3-, and 5-year actuarial
      survival rates were 97%, 74%, and 58%; median survival was 74 months. Tumor size
      > or =5 cm, >3 tumor nodules, and carcinoembryonic antigen level >200 ng/mL
      predicted poor survival (all P < 0.05). Median survival was 49 months in patients
      with positive margins and not yet reached in patients with negative margins (P =
      0.01). After hepatic resection, 225 (40.4%) patients had recurrence: 21 at the
      surgical margin, 56 at another intrahepatic site, 82 at an extrahepatic site, and
      66 at both intrahepatic and extrahepatic sites. Patients with negative margins of
      1 to 4 mm, 5 to 9 mm, and > or =1 cm had similar overall recurrence rates (P >
      0.05). Patients with positive margins were more likely to have surgical margin
      recurrence (P = 0.003). Adverse preoperative biologic factors including tumor
      number greater than 3 (P = 0.01) and a preoperative CEA level greater than 200
      ng/mL (P = 0.04) were associated with an increased risk of positive surgical
      margin. CONCLUSIONS: A positive margin after resection of hepatic colorectal
      metastases is associated with adverse biologic factors and increased risk of
      surgical-margin recurrence. The width of a negative surgical margin does not
      affect survival, recurrence risk, or site of recurrence. A predicted margin of <1
      cm after resection of hepatic colorectal metastases should not be used as an
      exclusion criterion for resection.

PMID- 15849508
TI  - Laparoscopic Heller myotomy provides durable relief from achalasia and salvages
      failures after botox or dilation.
AB  - OBJECTIVE: To report outcome after laparoscopic Heller myotomy in a large number
      of patients. SUMMARY BACKGROUND DATA: Laparoscopic Heller myotomy has been
      undertaken for over a decade, but most studies involve small numbers of patients
      with limited follow-up. METHODS: Since 1992, 262 patients have undergone
      laparoscopic Heller myotomy and been prospectively followed. Concomitant
      fundoplication was undertaken for a patulous hiatus or large hiatal hernia or to
      buttress the repair of an esophagotomy until recently when it became routinely
      applied. With mean follow-up at 32 months, symptoms were scored by patients on a
      Likert scale (frequency: 0 = Never to 10 = Every time I eat/always; severity: 0 =
      Not bothersome to 10 = Very bothersome). RESULTS: Before myotomy, 79% received
      Botox or bag dilation: 52% had Botox, 59% underwent dilation, and 36% had both.
      Inadvertent esophagotomy occurred in 5%. Concomitant diverticulectomy was
      undertaken in 4%, and fundoplication was undertaken in 30%. Complications were
      infrequent. Median length of stay was 1 day. After myotomy, the frequency and
      severity of symptoms of achalasia and reflux significantly decreased. Eighty
      eight percent of patients felt their symptoms were greatly improved or resolved,
      and 90% felt their outcome was satisfying or better. Ninety-three percent felt
      they would undergo myotomy again, if necessary. CONCLUSIONS: Laparoscopic Heller
      myotomy can safely and durably relieve symptoms of dysphagia while also reducing
      symptoms of reflux. Length of stay is short and patient satisfaction is very high
      with extended follow-up. Laparoscopic Heller myotomy is strongly encouraged for
      patients with symptomatic achalasia and is efficacious even after failures of
      dilation and/or Botox therapy.

PMID- 15849509
TI  - Utilization of the delay phenomenon improves blood flow and reduces collagen
      deposition in esophagogastric anastomoses.
AB  - OBJECTIVE: Complications of anastomotic healing are a common source of morbidity
      and mortality after esophagogastrostomy. The delay phenomenon is seen when a skin
      flap is partially devascularized in a staged procedure prior to its definitive
      placement, resulting in increased blood flow at the time of grafting. This effect
      may be applied to esophagogastrectomy, potentially reducing anastomotic
      complications. SUMMARY BACKGROUND DATA: The purpose of this investigation was to
      apply the delay principle to the gastrointestinal tract, investigate mechanisms
      by which it occurs and examine the effects of delay on anastomotic healing.
      METHODS: Thirty-seven opossums were assigned to Sham (n = 5), Immediate (n = 14),
      and Delay (n = 18) groups. Each underwent laparotomy and measurement of baseline
      gastric fundus blood flow. The Delay and Immediate animals underwent ligation of
      the left, right, and short gastric vessels and subsequent measurement of gastric
      fundus blood flow. The Delay group underwent repeat measurement of blood flow,
      esophagogastrectomy, gastric tubularization, and esophagogastrostomy 28 days
      after vessel ligation. The Immediate group completed the procedure immediately
      after vessel ligation. The anastomoses in both groups were harvested 32 days
      after esophagogastrostomy. The Sham group underwent blood flow measurement on
      initial laparotomy, followed by harvesting of esophagogastric junction 60 days
      later. Sections taken through the anastomoses were examined with trichrome
      staining and immunohistochemistry (IHC) for actin. Collagen content of the
      gastric submucosa 5 mm below the anastomosis was quantified, and preservation of
      the muscularis propria and muscularis mucosa was determined histologically.
      Capillary content of the esophagogastric junction was quantified using IHC for
      vascular endothelium in the Delay and Sham groups. RESULTS: Blood flow decreased
      by 73% following vessel ligation in Delay and Immediate groups. The Delay group
      had over 3 times the gastric blood flow of the Immediate group at the time of
      anastomosis at 16 (interquartile range [IQR] 11-17) versus 5, (IQR 5-6)
      mL/min/100 g (P = 0.000003). Two Immediate animals developed anastomotic leak and
      died; the Delay group had no complications. Submucosal collagen content in Sham,
      Delay, and Immediate groups were 57% (IQR 52-62), 65% (IQR 57-72), and 71% (IQR
      60-82), respectively (P = 0.0004). The median distance of full-thickness atrophy
      of the muscularis propria was 0.10 mm (IQR 0-0.60 mm) in the Delay group and 0.53
      mm (IQR 0.03-0.80 mm) in the Immediate group (P = 0.346). Five percent of the
      Delay group had atrophy of the muscularis mucosa, whereas 19% of Immediate
      animals had atrophy of this layer (P = 0.023). Compared with the Sham group, all
      Delay animals developed dilation of the right gastroepiploic artery and vein. A
      median of 27 (IQR 23-33) capillaries per 20x field was observed in the Sham
      fundus and 38 (IQR 31-46) in the Delay fundus (P = 0.037). CONCLUSIONS: The delay
      effect is associated with both vasodilation and angiogenesis and results in
      increased blood flow to the gastric fundus prior to esophagogastric anastomosis.
      Animals undergoing delayed operations have less anastomotic collagen deposition
      and ischemic injury than those undergoing immediate resection. Clinical
      application of the delay effect in patients undergoing esophagogastrectomy may
      lead to a decreased incidence of leak and stricture formation.

PMID- 15849511
TI  - Endogenous anabolic hormones and hypermetabolism: effect of trauma and gender
      differences.
AB  - OBJECTIVE: Protein degradation, negative nitrogen balance and compromised
      structure of essential organs have been associated with resistance and decreased
      production of anabolic hormones. In turn, increased levels of anabolic hormones
      are associated with improved survival. The aims of the present study were to
      determine the pattern of anabolic hormones, resting energy expenditure and
      cytokines in severely thermally injured pediatric patients and to compare these
      parameters in female and male patients. METHODS: Sixty-five children (1 to 16
      years of age) sustaining a severe thermal injury (> or =40% TBSA) were included
      into the study. Patients were further divided into females (n = 22) and males (n
      = 43). Patient demographics, nutritional support, incidence of sepsis, inhalation
      injury, and mortality were noted. Resting energy expenditure was measured during
      hospital course by indirect calorimetry. Blood was drawn 0, 10, 20, and 40 days
      postburn and serum insulin-like growth factor-I (IGF-I), insulin-like growth
      factor binding protein-1 and -3 (IGFBP-1, and -3), growth hormone, insulin, and
      cytokines were measured. RESULTS: There were no significant differences between
      females and males for demographics, nutritional intake, or concomitant injuries.
      In both groups, endogenous anabolic agents were drastically decreased by 3- to 5
      fold up to 40 days posttrauma. Females had significantly higher levels of IGF-I,
      IGFBP-3, growth hormone, and insulin when compared with males, P < 0.05.
      Increased levels of anabolic hormones were associated with decreased stay on the
      ICU (females 36 +/- 22 days versus males 53+/- 39 days), decreased serum IL-1beta
      and TNF-alpha as well as resting energy expenditure, P < 0.05. CONCLUSION: Data
      indicate that despite adequate nutritional support, severe thermal injury leads
      to decreased anabolic hormones over a prolonged period of time. Female patients
      had significantly increased levels of anabolic hormones, which are associated
      with decreased proinflammatory mediators and hypermetabolism, leading to a
      significant shorter ICU stay compared with male patients.

PMID- 15849510
TI  - Insulinlike growth factor-I-mediated migration and invasion of human colon
      carcinoma cells requires activation of c-Met and urokinase plasminogen activator
      receptor.
AB  - OBJECTIVE: To determine whether insulinlike growth factor-I (IGF-I) and
      hepatocyte growth factor (HGF) cooperate to induce migration and invasion of
      human colorectal carcinoma (CRC) cells and whether the effects of IGF-I and/or
      HGF are mediated through activation of the urokinase plasminogen activator
      (uPA)/uPA receptor (uPAR) system, a central mediator of tumor-cell migration and
      invasion. SUMMARY BACKGROUND DATA: CRC cells must invade through the basement
      membrane of the colon and migrate to form metastases. CRC cells are known to
      overexpress IGF-I receptor (IGF-IR), c-Met, and uPAR, 3 cell-surface receptors
      known to mediate cell migration and invasion. We hypothesized that IGF-IR and c
      Met cooperate to induce migration and invasion in CRC cells and that this
      signaling is dependent on uPAR. METHODS: KM12L4 human CRC cells were treated with
      IGF-I, HGF, or IGF-I + HGF in transwell migration and invasion chambers; cells
      that had migrated or invaded were counted. To determine the role of c-Met in IGF
      I-induced migration and invasion, c-Met was inhibited by infection of cells with
      an adenovirus containing a c-Met ribozyme; transwell assays were then repeated.
      To determine the role of the uPA/uPAR system in IGF-I-induced CRC cell migration
      and invasion, transwell assays were repeated after pretreating cells with the uPA
      inhibitor amiloride or with neutralizing antibodies to uPA and uPAR. RESULTS: IGF
      I and HGF, alone or in combination, increased cell migration and invasion. The c
      Met ribozyme inhibited IGF-I- and HGF-mediated migration and invasion, indicating
      that c-Met is essential for these processes. uPA and uPAR inhibition blocked IGF
      I- and HGF-mediated migration and invasion, suggesting that uPAR is downstream of
      IGF/IGF-IR and HGF/c-Met in the signaling pathways that mediate cell migration
      and invasion. CONCLUSIONS: IGF-I and HGF cooperate to induce migration and
      invasion of CRC cells, and c-Met and uPA/uPAR are required for IGF-I-mediated
      migration and invasion. In our in vitro model of CRC migration and invasion, uPA
      and uPAR appear to be downstream of IGF-IR and c-Met and are required for
      migration and invasion. Elucidation of the pathways that contribute to tumor
      progression and metastasis should provide a foundation for the rational
      development and use of targeted therapies for CRC.

PMID- 15849512
TI  - Effective treatment of biliary cystadenoma.
AB  - OBJECTIVE: Evaluate experience over 15 years with treatment of this lesion.
      SUMMARY BACKGROUND DATA: Biliary cystadenoma, a benign hepatic tumor arising from
      Von Meyenberg complexes, usually present as septated intrahepatic cystic lesions.
      METHODS: Data were collected concurrently and retrospectively on patients
      identified from hospital medical records reviewed for pertinent International
      Classification of Diseases, Ninth Revision, Clinical Modification and CPT codes,
      pathology logs, and from operative case logs. Pathology specimens were rereviewed
      to confirm the diagnosis of biliary cystadenoma or biliary cystadenocarcinoma by
      2 GI pathologists. RESULTS: From October 1989 to April 2004 at our institution,
      19 (18F:1M) patients had pathologically confirmed biliary cystadenomas, including
      one with a biliary cystadenocarcinoma. The mean age was 48 +/- 15 years at
      initial evaluation. Complaints included abdominal pain in 74%, abdominal
      distension in 26%, and nausea/vomiting in 11%. Only 1 patient presented with an
      incidental finding. Symptoms had been present for 3 +/- 5 years, with 1 to 4
      different surgeons and many other physicians involved in the diagnosis or
      treatment prior to definitive ablation. Eight patients had undergone 20 previous
      treatments, including multiple percutaneous aspirations in 4 and 11 operative
      procedures. CT or US was diagnostic in 95%, with internal septations present in
      the hepatic cysts. Definitive operative intervention consisted of hepatic
      resection in 12 patients, enucleation in 6 patients, and fenestration and
      complete fulguration in 1 patient. There were no perioperative deaths. No
      recurrences were observed after definitive therapy, with follow-up of 4 +/- 4
      years. CONCLUSIONS: Biliary cystadenoma must be recognized and treated
      differently than most hepatic cysts. There remains a need for education about the
      imaging findings for biliary cystadenoma to reduce the demonstrated delay in
      appropriate treatment. Traditional treatment of simple cysts such as aspiration,
      drainage, and marsupialization results in near universal recurrence and
      occasional malignant degeneration. This experience demonstrates effective options
      include total ablation by standard hepatic resection and cyst enucleation.

PMID- 15849513
TI  - Neuroendocrine hepatic metastases: does aggressive management improve survival?
AB  - OBJECTIVE: The aim of this study was to determine whether aggressive management
      of neuroendocrine hepatic metastases improves survival. SUMMARY BACKGROUND DATA:
      Survival in patients with carcinoid and pancreatic neuroendocrine tumors is
      significantly better than adenocarcinomas arising from the same organs. However,
      survival and quality of life are diminished in patients with neuroendocrine
      hepatic metastases. In recent years, aggressive treatment of hepatic
      neuroendocrine tumors has been shown to relieve symptoms. Minimal data are
      available, however, to document improved survival with this approach. METHODS:
      The records of patients with carcinoid (n = 84) and pancreatic neuroendocrine
      tumors (n = 69) managed at our institution from January 1990 through July 2004
      were reviewed. Eighty-four patients had malignant tumors, and hepatic metastases
      were present in 60 of these patients. Of these 60 patients, 23 received no
      aggressive treatment of their liver metastases, 19 were treated with hepatic
      resection and/or ablation, and 18 were managed with transarterial
      chemoembolization (TACE) frequently (n = 11) in addition to resection and/or
      ablation. These groups did not differ with respect to age, gender, tumor type, or
      extent of liver involvement. RESULTS: Median and 5-year survival were 20 months
      and 25% for the Nonaggressive group, >96 months and 72% for the
      Resection/Ablation group, and 50 months and 50% for the TACE group. The survival
      for the Resection/Ablation and the TACE groups was significantly better (P <
      0.05) when compared with the Nonaggressive group. Patients with more than 50%
      liver involvement had a poor outcome (P < 0.001). CONCLUSIONS: These data suggest
      that aggressive management of neuroendocrine hepatic metastases does improve
      survival, that chemoembolization increases the patient population eligible for
      this strategy, and that patients with more than 50% liver involvement may not
      benefit from an aggressive approach.

PMID- 15849514
TI  - Surgical management of bile duct injuries sustained during laparoscopic
      cholecystectomy: perioperative results in 200 patients.
AB  - OBJECTIVE: A single institution retrospective analysis of 200 patients with major
      bile duct injuries was completed. Three patients died without surgery due to
      uncontrolled sepsis. One hundred seventy-five patients underwent surgical repair,
      with a 1.7% postoperative mortality and a complication rate of 42.9%. SUMMARY
      BACKGROUND DATA: The widespread application of laparoscopic cholecystectomy (LC)
      has led to a rise in the incidence of major bile duct injuries (BDI). Despite the
      frequency of these injuries and their complex management, the published
      literature contains few substantial reports regarding the perioperative
      management of BDI. METHODS: From January 1990 to April 2003, a prospective
      database of all patients with a BDI following LC was maintained. Patients' charts
      were retrospectively reviewed to analyze perioperative surgical management.
      RESULTS: Over 13 years, 200 patients were treated for a major BDI following LC.
      Patient demographics were notable for 150 women (75%) with a mean age of 45.5
      years (median 44 years). One hundred eighty-eight sustained their BDI at an
      outside hospital. The mean interval from the time of BDI to referral was 29.1
      weeks (median 3 weeks). One hundred nine patients (58%) were referred within 1
      month of their injury for acute complications including bile leak, biloma, or
      jaundice. Twenty-five patients did not undergo a surgical repair at our
      institution. Three patients (1.5%) died after delayed referral before an attempt
      at repair due to uncontrolled sepsis. Twenty-two patients, having intact biliary
      enteric continuity, underwent successful balloon dilatation of an anastomotic
      stricture. A total of 175 patients underwent definitive biliary reconstruction,
      including 172 hepaticojejunostomies (98%) and 3 end-to-end repairs. There were 3
      deaths in the postoperative period (1.7%). Seventy-five patients (42.9%)
      sustained at least 1 postoperative complication. The most common complications
      were wound infection (8%), cholangitis (5.7%), and intraabdominal abscess/biloma
      (2.9%). Minor biliary stent complications occurred in 5.7% of patients. Early
      postoperative cholangiography revealed an anastomotic leak in 4.6% of patients
      and extravasation at the liver dome-stent exit site in 10.3% of patients.
      Postoperative interventions included percutaneous abscess drainage in 9 patients
      (5.1%) and new percutaneous transhepatic cholangiography and stent placement in 4
      patients (2.3%). No patient required reoperation in the postoperative period. The
      mean postoperative length of stay was 9.5 days (median 9 days). The timing of
      operation (early, intermediate, delayed), presenting symptoms, and history of
      prior repair did not affect the incidence of the most common perioperative
      complications or length of postoperative hospital stay. CONCLUSIONS: This series
      represents the largest single institution experience reporting the perioperative
      management of BDI following LC. Although perioperative complications are
      frequent, nearly all can be managed nonoperatively. Early referral to a tertiary
      care center with experienced hepatobiliary surgeons and skilled interventional
      radiologists would appear to be necessary to assure optimal results.

PMID- 15849515
TI  - Perianal Crohn disease: predictors of need for permanent diversion.
AB  - OBJECTIVE: Fissures, fistulas, abscesses, and anal canal stenosis are
      manifestations of perianal Crohn disease (CD). There are no known predictors of
      which patients will fail sphincter-sparing surgical therapy and ultimately
      require fecal diversion. METHODS: Of 356 consecutive patients with CD, 24% (86)
      had perianal CD (age range, 14-83 years), and women were slightly more frequently
      affected. Clinical variables were examined for factors predictive of the need for
      permanent fecal diversion. RESULTS: CD associated with perianal CD was limited to
      the small bowel and/or ileocolic area in 23% of patients; the remainder had
      colorectal CD. Eighty-six patients underwent 344 operations. Forty-two patients
      (49%) ultimately required permanent diversion; among them were 21 of 32 patients
      (66%) with anal stricture and 12 of 20 women (60%) with rectovaginal fistula.
      Univariate analyses of clinical variables were performed with respect to need for
      permanent fecal diversion. Significant univariate predictors were the presence of
      colonic CD (P = 0.0045, odds ratio [OR] 5.4), avoidance of ileocolic resection (P
      = 0.0147, OR 0.4), and the presence of an anal stricture (P = 0.0165, OR 3.0). In
      multivariate logistic regression, the presence of colonic disease and anal canal
      stricture were predictors of permanent diversion. The OR associated with the risk
      of permanent diversion in the presence of colonic disease and in the absence of
      anal stricture was 10 (P = 0.0345). In the presence of both colonic disease and
      anal canal stenosis, the OR associated with permanent stoma was 33 (P = 0.0023).
      CONCLUSIONS: The management of perianal CD continues to be challenging. Roughly
      half of patients required permanent fecal diversion, which was even more
      frequently true for patients with colonic CD and anal stenosis. Recognizing these
      tendencies will assist both patients and surgeons in planning optimal treatment.

PMID- 15849516
TI  - Prevalence of blood-borne pathogens in an urban, university-based general
      surgical practice.
AB  - OBJECTIVE: To measure the current prevalence of blood-borne pathogens in an
      urban, university-based, general surgical practice. SUMMARY BACKGROUND DATA:
      Human immunodeficiency virus (HIV), hepatitis B, and hepatitis C represent
      significant occupational hazards to the surgeon. While the incidence of these
      blood-borne pathogens is increasing in the general population, little is known
      about the current prevalence of these exposures among patients presenting for
      surgery. METHODS: We studied 709 consecutive operative cases (July 2003 to June
      2004) in a university practice that provides all inpatient, emergency department,
      and outpatient consultative general surgical services. Trauma cases and bedside
      procedures were excluded. Data collected included HIV, hepatitis B and C test
      results, type of operation, age, sex, and history of intravenous drug use.
      RESULTS: Testing for blood-borne pathogens was performed in 53% (N = 373) of 709
      patients based on abnormal liver function tests, neutropenia, history of IV drug
      use, or patient request. Thirty-eight percent of all operations (142/373) were
      found to involve a blood-borne pathogen when tested: HIV (26%), hepatitis B (4%),
      hepatitis C (35%), and coinfection with HIV and hepatitis C (17%). Forty-seven
      percent of men tested positive for at least 1 blood-borne pathogen. Seventy-three
      different types of operations were performed, ranging from Whipple procedures to
      amputations. Soft-tissue abscess procedures 48% (34/71) and lymph node biopsies
      67% (10/15) (P < 0.01) were most often associated with blood-borne pathogens.
      Infections were more common among men (P < 0.01), patients 41 to 50 years of age
      (P < 0.01), and patients with a history of intravenous drug use (P < 0.01).
      CONCLUSIONS: HIV and hepatitis C infections are common in an urban university
      general surgical practice, while hepatitis B is less common. In addition, certain
      operations are associated with significantly increased exposure rates. Given the
      high incidence of these infections, strategies such as sharpless surgical
      techniques should be evaluated and implemented to protect surgeons from blood
      borne pathogens.

PMID- 15849517
TI  - Proposed revision of the esophageal cancer staging system to accommodate
      pathologic response (pP) following preoperative chemoradiation (CRT).
AB  - OBJECTIVE: To determine the impact of pathologic response following preoperative
      chemoradiation (CRT) on the AJCC esophageal cancer staging system. SUMMARY
      BACKGROUND DATA: Increasing numbers of locoregionally advanced esophageal cancer
      patients are treated with preoperative CRT prior to surgical resection. METHODS:
      Five hundred ninety-three pts from 1985 to 2003 with esophageal cancer who
      underwent surgery with (n = 239) or without CRT (n = 354) were reviewed. Resected
      esophageal tumors were assessed for pathologic response by determining extent of
      residual tumor following CRT (P0, 0% residual; P1, 1%-50% residual; P2, >50%
      residual). RESULTS: After CRT down-staging, pTNM specific survival was similar,
      irrespective of treatment group (P = 0.98). The pTNM stage distribution was more
      favorable in the CRT group (P < 0.001) despite a more advanced initial cTNM stage
      distribution (P < 0.001). Following CRT, the pathologic response (pP) at the
      primary tumor as defined by extent of residual tumor predicted overall survival
      (3 years: P0, 0% residual = 74%; P1, 1%-50% residual = 54%; P2, >50% residual =
      24%, P < 0.001) and stage specific survival with greater accuracy than pTNM stage
      alone. CONCLUSIONS: Our analyses demonstrate that following CRT, pTNM continues
      to predict survival. The extent of pathologic response following CRT is an
      independent risk factor for survival (pP) and should be incorporated in the pTNM
      esophageal cancer staging system to better predict patient outcome in esophageal
      cancer.

PMID- 15849518
TI  - Impact of obesity on resource utilization for general surgical procedures.
AB  - OBJECTIVE: To determine the impact of the obesity epidemic on workload for
      general surgeons. SUMMARY BACKGROUND DATA: In 2001, the prevalence of obesity in
      the United States reached 26%, more than double the rate in 1990. This study
      focuses on the impact of obesity on surgical practice and resource utilization.
      METHODS: A retrospective analysis was done on patients undergoing
      cholecystectomy, unilateral mastectomy, and colectomy from January 2000 to
      December 2003 at a tertiary care center. The main outcome variables were
      operative time (OT), length of stay (LOS), and complications. The key independent
      variable was body mass index. We analyzed the association of obesity status with
      OT, LOS, and complications for each surgery, using multivariate regression models
      controlling for surgeon time-invariant characteristics. RESULTS: There were 623
      cholecystectomies, 322 unilateral mastectomies, and 430 colectomies suitable for
      analysis from 2000 to 2003. Multivariable regression analyses indicated that
      obese patients had statistically significantly longer OT (P < 0.01) but not
      longer LOS (P > 0.05) or more complications (P > 0.05). Compared with a normal
      weight patient, an obese patient had an additional 5.19 (95% confidence interval
      [CI], 0.15-10.24), 23.67 (95% CI, 14.38-32.96), and 21.42 (95% CI, 9.54-33.30)
      minutes of OT with respect to cholecystectomy, unilateral mastectomy, and
      colectomy. These estimates were robust in sensitivity analyses. CONCLUSIONS:
      Obesity significantly increased OT for each procedure studied. These data have
      implications for health policy and surgical resource utilization. We suggest that
      a CPT modifier to appropriately reimburse surgeons caring for obese patients be
      considered.

PMID- 15849519
TI  - Long-term oncologic outcome following preoperative combined modality therapy and
      total mesorectal excision of locally advanced rectal cancer.
AB  - OBJECTIVE: Our aims were to (1) determine the long-term oncologic outcome for
      patients with rectal cancer treated with preoperative combined modality therapy
      (CMT) followed by total mesorectal excision (TME), (2) identify factors
      predictive of oncologic outcome, and (3) determine the oncologic significance of
      the extent of pathologic tumor response. SUMMARY BACKGROUND DATA: Locally
      advanced (T3-4 and/or N1) rectal adenocarcinoma is commonly treated with
      preoperative CMT and TME. However, the long-term oncologic results of this
      approach and factors predictive of a durable outcome remain largely unknown.
      METHODS: Two hundred ninety-seven consecutive patients with locally advanced
      rectal adenocarcinoma at a median distance of 6 cm from the anal verge (range 0
      15 cm) were treated with preoperative CMT (radiation: 5040 centi-Gray (cGy) and 5
      fluorouracil (5-FU)-based chemotherapy) followed by TME from 1988 to 2002. A
      prospectively collected database was queried for long-term oncologic outcome and
      predictive clinicopathologic factors. RESULTS: With a median follow-up of 44
      months, the estimated 10-year overall survival (OS) was 58% and 10 year
      recurrence-free survival (RFS) was 62%. On multivariate analysis, pathologic
      response >95%, lymphovascular invasion and/or perineural invasion (PNI), and
      positive lymph nodes were significantly associated with OS and RFS. Patients with
      a >95% pathologic response had a significantly improved OS (P = 0.003) and RFS (P
      = 0.002). CONCLUSIONS: Treatment of locally advanced rectal cancer with
      preoperative CMT followed by TME can provide for a durable 10-year OS of 58% and
      RFS of 62%. Patients who achieve a >95% response to preoperative CMT have an
      improved long-term oncologic outcome, a novel finding that deserves further
      study.

PMID- 15849520
TI  - von Willebrand factor: the new treatment paradigm--introduction.

PMID- 15849521
TI  - Shear stress and the role of high molecular weight von Willebrand factor
      multimers in thrombus formation.
AB  - High molecular weight von Willebrand factor (VWF) multimers have an important
      role in the formation of platelet thrombi under conditions of high shear stress
      resulting from rapid blood flow. Laboratory studies conducted using an
      endothelial cell system have shown that ultra-large VWF multimers (ULVWF) attach
      to the surface of histamine-stimulated endothelial cells and form large string
      like structures to which platelets adhere. Platelet attachment is mediated
      through the interaction of the glycoprotein (Gp) Ibalpha subunit of the platelet
      GpIb-IX-V complex with the A1 domain of VWF. These platelet-ULVWF strings are
      rapidly cleaved by the addition of normal human plasma or the purified plasma
      metalloprotease ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin
      type I motifs domains). Cleaving activity is absent from the plasma of patients
      with the congenital or acquired forms of thrombotic thrombocytopenic purpura
      (TTP) and from mixtures of normal plasma with plasma from patients with acquired
      TTP. The interaction of VWF with P-selectin is at least partially responsible for
      the attachment of the VWF strings to the endothelium. Increased tensile stress on
      ULVWF multimers resulting from the tethering of ULVWF strings to the endothelial
      surface by P-selectin in flowing blood may expose the cleavage site on the A2
      domain of VWF, facilitating multimer degradation by ADAMTS-13. These studies have
      important implications in bleeding and thrombotic disorders, including von
      Willebrand disease and TTP.

PMID- 15849522
TI  - Management of von Willebrand disease with factor VIII/von Willebrand factor
      concentrates: results from current studies and surveys.
AB  - Until the mid 1980s, cryoprecipitate had been the mainstay of treatment of
      patients with von Willebrand disease (VWD) who were unresponsive to desmopressin.
      The advent of virally inactivated factor VIII/von Willebrand factor (FVIII/VWF)
      concentrates, originally developed for the treatment of patients with hemophilia,
      provided improved therapy for VWD. These products were therefore introduced in
      clinical practice in most European hemophilia centers; one concentrate (Humate-P)
      was approved for management of VWD in the USA. The 1980s saw the first clinical
      studies of FVIII/VWF concentrates in patients with VWD, but a standardized
      procedure for ex vivo effects of these virus-inactivated plasma concentrates in
      VWD patients became available only in 1992. Study results have shown that the
      commercially available VWF-containing concentrates are effective in clinical
      practice (bleeding and surgery), producing responses that may differ depending on
      the patient's VWD subtype; infusion results in correction of factor VIII activity
      (FVIII:C) and ristocetin cofactor activity of VWF (VWF:RCo), whereas bleeding
      time is not consistently corrected. Several studies have demonstrated that
      FVIII/VWF concentrates have variable VWF multimer patterns relative to normal
      human plasma. New products should be validated by current methodologies before
      introduction in clinical practice. Data on several intermediate-purity and high
      purity FVIII/VWF concentrates have been reported, and a large prospective study
      of an intermediate-purity FVIII/VWF concentrate (Haemate P/Humate-P) is currently
      in progress. In the latter study, for the first time, the appropriate dosage to
      prevent bleeding during surgery is being calculated on the basis of scheduled
      pharmacokinetic assessments in each patient. Although thrombotic events are rare
      in patients with VWD receiving repeated infusions of FVIII/VWF concentrates,
      there is some concern that sustained high concentrations of FVIII:C may increase
      the risk of postoperative venous thromboembolism. On the basis of these
      observations, the dosage and timing of FVIII/VWF administration should be planned
      to keep FVIII:C concentrations between 50 U/dl and 150 U/dl in the postoperative
      period.

PMID- 15849523
TI  - Long-term prophylaxis in von Willebrand disease.
AB  - The majority of patients with von Willebrand disease (VWD) have a mild bleeding
      tendency that primarily involves mucosal bleeding. Some patients with the
      disorder, however, have severe episodes of mucosal or joint bleeding that can
      hamper daily activities and lead to significant joint impairment. Experience in
      the setting of severe hemophilia has shown the feasibility and benefits of
      prophylactic treatment to prevent bleeding and development of arthropathy. This
      approach also needs to be evaluated in patients with VWD who require repetitive
      treatment for bleeding episodes. Data from a series of 35 patients (with VWD
      types 3, 2A, 2B, and 1) who have received long-term prophylaxis at Malmo
      University Hospital and Karolinska University Hospital in Stockholm, Sweden, have
      demonstrated a substantial reduction of bleeding episodes since initiation of
      treatment. Patients who began prophylaxis at a young age (younger than 5 years)
      to prevent nose and mouth bleeds have had no joint bleeds and have no clinical
      signs of arthropathy. Treatment has been safe, with no cases of thrombosis, and
      no viral transmission among patients who received virus-attenuated von Willebrand
      factor-containing factor VIII concentrate. These data thus suggest that long-term
      prophylaxis is warranted in the majority of patients with type 3 VWD and in other
      subtypes with severe bleeding tendencies, and that such an approach may help in
      the avoidance of joint disease if started early. More clinical data and
      controlled trials are needed in order to formulate recommendations for
      prophylaxis in patients with VWD.

PMID- 15849524
TI  - Role of von Willebrand factor in immune tolerance induction.
AB  - Patients with hemophilia who develop inhibitors present a particular challenge in
      therapeutic management. Although such patients are at high risk for severe
      bleeding episodes, the optimal treatment approach--prophylaxis--is ineffective
      unless inhibitors are eliminated. Several protocols for immune tolerance
      induction have been used. Success rates may vary depending both on patient
      variables and on factors related to the therapeutic regimen, including
      concentrate purity and von Willebrand factor (VWF) content. Several in vitro
      studies testing inhibitor plasma samples against various factor VIII (FVIII)
      concentrates have shown lower FVIII inhibitor titer compared with concentrates
      with greater VWF content. Recent in vivo observations also support the importance
      of VWF content, based on evidence of reduced rates of success of immune tolerance
      induction with use of the high-purity FVIII products that became available in the
      early 1990s. Current data thus support use of FVIII concentrates containing VWF
      in immune tolerance induction; other variables may also contribute to the
      relative success of this treatment. Studies are needed to delineate these
      variables in order to improve management of this potentially devastating
      complication of hemophilia treatment.

PMID- 15849525
TI  - The evolving classification of von Willebrand disease.
AB  - The classification of von Willebrand disease (VWD) has been refined since its
      first description in the 1920s, as knowledge regarding clinical symptoms and
      tests of von Willebrand factor (VWF) activity and multimer composition have
      increased. Current molecular approaches have allowed better understanding of the
      biosynthesis and function of VWF, and made possible phenotype-genotype studies of
      VWD subtypes. Improved classification of this heterogeneous disorder based on
      reproducible correlations between specific genetic mutations and recognized
      phenotypes should aid in determining appropriate management of patients with VWD.

PMID- 15849526
TI  - Estimates of primary and secondary syphilis rates in persons with HIV in the
      United States, 2002.
AB  - BACKGROUND: In the United States, there is a high rate of HIV coinfection in
      persons with syphilis. GOAL: The goal of this study was to estimate the rate of
      primary and secondary (P&S) syphilis in persons living with HIV in the United
      States in 2002. STUDY: We approximated the number of new cases of P&S syphilis in
      HIV-infected persons and divided this by the estimated number of persons living
      with HIV. Values for the calculations were obtained from national syphilis and
      HIV/AIDS surveillance reports and other published sources. RESULTS: We estimated
      the rate of new cases of P&S syphilis at 186 per 100,000 persons living with HIV
      in 2002, 25 per 100,000 HIV-infected women, 60 per 100,000 HIV-infected men who
      have sex with women only, and 336 per 100,000 HIV-infected men who have sex with
      men. Of the 6862 reported cases of P&S syphilis in 2002, an estimated 1718 (25%)
      occurred in persons coinfected with HIV. CONCLUSIONS: The estimated rate of P&S
      syphilis in persons with HIV is considerably higher than that of the general
      population. These findings highlight the importance of providing sexually
      transmitted disease prevention and control services to HIV-infected persons.

PMID- 15849527
TI  - Heterosexual transmission of HIV in China: a systematic review of behavioral
      studies in the past two decades.
AB  - OBJECTIVE: The objective of this study was to address the role of heterosexual
      transmission of HIV in China. GOAL: The goal of this study was to explore the
      prevalence of unsafe sex and the likelihood of HIV spread heterosexually from
      core populations to others. STUDY: The authors conducted a review of behavioral
      studies. RESULTS: Drug users were more likely to be involved in higher-risk
      sexual behaviors than were those who abstained from using drugs. Most female drug
      users (52-98%) reported having engaged in commercial sex. Most female sex workers
      (FSWs) and individuals with sexually transmitted diseases (STDs) had concurrent
      sexual partners. Many continued to have unprotected sex after noticing STD
      symptoms in themselves or their sexual partners. From 5% to 26% of rural-to-urban
      migrants had multiple sexual partners and 10% of males patronized FSWs during
      migration. CONCLUSIONS: Factors such as high rates of FSW patronage, low rates of
      condom use during commercial sex, having sex with both commercial and
      noncommercial sexual partners, and high rates of STD infection may promote a
      heterosexual epidemic in China.

PMID- 15849528
TI  - Staff affirmations and client criticisms: staff and client perceptions of quality
      of care at sexually transmitted disease clinics.
AB  - OBJECTIVES: Public health sexually transmitted disease (STD) clinics play a
      central role in STD control efforts. This study addressed the perceived quality
      of client services at two STD clinics in Alabama. GOAL: The goal of this study
      was to evaluate and develop tools for assessment of client satisfaction at STD
      clinics. STUDY: Four focus groups of staff (N=16) and clients (N=15) at the
      clinics were conducted between June and November 2003. RESULTS: Staff and client
      assessments of respect, privacy protections, and friendliness at the clinics
      differed in substantial ways. Clients were concerned with visibility, being
      stigmatized or disrespected, and about a breach of confidentiality. Concerns
      about being stigmatized focused mainly on nonclinical staff. The staff did not
      perceive these concerns to be warranted. Quality of medical care was rated high
      by both groups. CONCLUSION: Staff-client interactions are an important element of
      STD care, and "front desk" actions set the tone at public STD clinics.
      Nonclinicians should receive training to improve body language and other
      behaviors to alleviate the stigma concerns of clients who are anxious, fearful,
      and sometimes distrustful of the health system.

PMID- 15849529
TI  - Characteristics and sexually transmitted diseases of male rural migrants in a
      metropolitan area of Eastern China.
AB  - GOAL: The goal of this study was to identify the correlates and determine the
      prevalence of sexually transmitted diseases (STDs) among male rural migrants in
      Shanghai, China. STUDY: The authors conducted a community-based cross-sectional
      study with an anonymous questionnaire interview and collection of blood and first
      void urine samples for STD screening. RESULTS: One thousand eighty-six (85.3%) of
      1273 male rural migrants approached were interviewed. Among the 986 sexually
      active migrants, the prevalence of chlamydia, gonorrhea, and syphilis was 3.5%,
      0.5%, and 1.0%, respectively. None were infected with HIV. The prevalence of STDs
      was 3.2% for construction workers, 5.6% for market vendors, and 5.6% for factory
      workers. Risk factors for STDs were longer duration in Shanghai, frequent
      hometown visits, having multiple sex partners, and the desire to have multiple
      sex partners. CONCLUSIONS: The prevalence of STDs among male rural migrants is
      relatively low. Maintaining the current low prevalence can reduce the risk of an
      HIV epidemic among Shanghai migrants, but prevention messages need to be tailored
      to the low level of literacy in many migrants.

PMID- 15849530
TI  - Predictors of chronic pelvic pain in an urban population of women with symptoms
      and signs of pelvic inflammatory disease.
AB  - OBJECTIVE: The objective of this study was to assess the risk profile for chronic
      pelvic pain (CPP) after pelvic inflammatory disease (PID). STUDY: Multivariate
      logistic regression was used to assess risk factors for CPP in a longitudinal
      study of 780 predominately black, urban women with clinically suspected PID:
      complaints of acute pain (<30 days); a clinical finding of pelvic tenderness; and
      leukorrhea, mucopurulent cervicitis, or untreated gonococcal or chlamydial
      cervicitis. CPP was defined as pain reported at >or=2 consecutive interviews
      conducted every 3 to 4 months for 2 to 5 years. RESULTS: Nonblack race (odds
      ratio [OR], 2.17; 95% confidence interval [CI], 1.31-3.58), being married (OR,
      2.06; 95% CI, 1.02-4.18), a low SF-36 mental health composite score (OR, 2.71;
      95% CI, 1.69-4.34), >or=2 prior PID episodes (OR, 2.84; 95% CI, 1.07-7.54), and
      smoking (OR, 1.65; 95% CI, 1.01-2.71) independently predicted CPP. Histologic
      endometritis or evidence of endometrial Neisseria gonorrhoeae or Chlamydia
      trachomatis infection was negatively associated with CPP (OR, 0.69; 95% CI, 0.44
      1.10). CONCLUSIONS: A range of demographic, clinical, historical, and behavioral
      factors predict CPP after PID.

PMID- 15849531
TI  - Use of male condoms during and after randomized, controlled trial participation
      in Cameroon.
AB  - BACKGROUND AND OBJECTIVE: This study evaluated patterns of long-term use of male
      condoms among partners of 966 Cameroonian women who received eight intensive,
      monthly counseling sessions about condoms and sexually transmitted infection
      testing and treatment. METHOD: An interrupted time-series design was used with
      study participants reporting condom use and other covariates at enrollment,
      monthly for 6 months during the randomized, controlled trial, and at
      approximately 14 months after the trial. RESULTS: Consistent condom use began
      decreasing while women were still receiving monthly condom use counseling, with
      every month in the trial associated with an odds ratio of 0.96 (95% confidence
      interval [CI], 0.94-0.99) of consistent condom use and dropped substantively
      after the trial with a 0.39 (95% CI, 0.26-0.59) odds ratio in a logistic
      regression analysis. The incidence of unprotected coital acts as each month
      passed increased by 3% (95% CI, 1-4%) with no statistically significant change
      during the condom use follow-up survey as indicated in a zero-inflated Poisson
      regression model for unprotected coital acts. Condom use in a coital act was 0.84
      (95% CI, 0.78-0.92) less likely during the follow-up survey than during the
      trial. CONCLUSION: Only a few women sustained consistent condom use throughout
      the study period and for more than 1 year after. It is important to continue
      documenting the impact of condom promotion in a rigorous manner and to identify
      content and delivery of counseling that will lead to sustained condom use beyond
      the intervention period.

PMID- 15849532
TI  - Demographic, behavioral, and knowledge factors associated with herpes simplex
      virus type 2 infection among men whose current female partner has genital herpes.
AB  - OBJECTIVE/GOAL: The objective of this study was to evaluate risk factors for
      herpes simplex virus type 2 (HSV-2) infection among men whose female partners
      have genital herpes (GH). STUDY: Between 1998 and 2001, 717 men in heterosexual
      monogamous relationships, without a history of GH, completed a cross-sectional
      questionnaire on demographic, behavioral, and knowledge factors for GH. Their
      female partners were symptomatic and HSV-2-seropositive. Risk factors for HSV-2
      seropositivity were assessed using logistic regression. RESULTS: On laboratory
      confirmation, 25% of the men were HSV-2-seropositive. Factors significantly
      (P<0.01) associated with HSV-2 infection included: never using condoms (adjusted
      odds ratio [aOR], 1.84; 95% confidence interval [CI], 1.15-2.95), prior sexually
      transmitted disease (STD) (aOR, 1.80; CI, 1.27-2.58), vaginal intercourse during
      symptomatic episodes (aOR, 1.77; CI, 1.19-2.62), longer partnership (for each
      additional year aOR, 1.07; CI, 1.03-1.09), and lower knowledge of GH (aOR, 1.14;
      CI, 1.05-1.23). CONCLUSION: Potentially modifiable risk factors for HSV-2
      infection included engaging in vaginal sex during symptomatic episodes, never
      using condoms, and lower knowledge of GH.

PMID- 15849533
TI  - Increased incidence of squamous cell anal cancer among men with AIDS in the era
      of highly active antiretroviral therapy.
AB  - OBJECTIVE: We sought to determine if the introduction of highly active
      antiretroviral therapy (HAART) corresponded with changes in anal squamous cell
      cancer rates among men with AIDS. STUDY: We linked cancer registry data from 1988
      2000 and AIDS registry data from 1981-July/2003 for San Diego County. We defined
      1991-1995 and 1996-2000 as the pre- and post-HAART periods, respectively.
      RESULTS: The annual incidence of invasive anal cancer increased from zero per
      100,000 men with AIDS aged 25 to 64 years (95% confidence interval [CI], 0-226)
      in 1991 to 224 per 100,000 (95% CI, 102-425) in the year 2000. Pre-HAART, the
      average annual incidence of invasive anal cancer was 49 per 100,000 men with AIDS
      aged 25 to 64 years (95% CI, 16-114) versus 144 per 100,000 (95% CI, 93-212) post
      HAART. The relative risk of invasive anal cancer among men with AIDS compared
      with men without known HIV/AIDS was 98 (95% CI, 36-264) pre-HAART and 352 (95%
      CI, 186-669) post-HAART. The increased incidence of anal cancer among men with
      AIDS resulted in an increase in the overall rate of anal cancer among men in San
      Diego County. CONCLUSIONS: The rising incidence of anal cancer among men with
      AIDS may be related to increased longevity with HAART and the consequent
      increased time at risk for the development of malignancy and/or the result of
      greater use of cytologic screening.

PMID- 15849534
TI  - Community planning, HIV prevention, and a needs assessment for men who have sex
      with men: the South Beach Health Survey.
AB  - OBJECTIVE: The objective of this study was to plan for a series of culturally
      competent and sexually appropriate public health interventions for a highly
      mobile population of men who have sex with men (MSM). GOAL: The goal of this
      study was to conduct a comprehensive needs assessment. STUDY: A cross-sectional
      survey with a multistage probability sample of unmarried adult MSM living in
      households was conducted. RESULTS: A total of 918 residential units were
      screened, 154 eligible men were identified, and 140 mostly white (56%) and
      Hispanic (34%) MSM (median=33.5 years old) were enrolled (90.9% response rate).
      Almost half (47%) reported engaging in unprotected anal intercourse in the
      previous 12 months. Drug use was common. Almost one third (31.0%) tested positive
      for the HIV antibody. Estimated annual incidence of HIV infection was 10.0%.
      CONCLUSIONS: Population-based HIV antibody testing revealed a remarkably high
      annual incidence of HIV infection. A community-based organization was transformed
      to implement a social marketing campaign and provide other disease prevention
      services for MSM.

PMID- 15849535
TI  - Acceptance of herpes simplex virus type 2 screening among sexually transmitted
      disease clinic clients.

PMID- 15849536
TI  - Reepithelialized orthotopic tracheal allografts expand memory cytotoxic T
      lymphocytes but show no evidence of chronic rejection.
AB  - BACKGROUND: Acute rejection of mouse tracheal allografts is characterized by
      infiltration of the lamina propria with CD4+/CD8+ T cells that leads to the
      destruction of the epithelium and luminal obliteration. The donor epithelium is
      progressively replaced by recipient-derived epithelium. Once allograft
      reepithelialization has occurred, immunosuppression can be withdrawn without
      inciting acute rejection. We hypothesize that reepithelialization will also
      prevent chronic rejection of the trachea after withdrawal of immunosuppression.
      METHODS: BALB/c tracheal grafts were transplanted orthotopically into allogeneic
      C57BL/6 recipients. Allografted mice were nonimmunosuppressed for 10 or 100 days
      or immunosuppressed with cyclosporine A continuously for 50 days and then
      withdrawn from immunosuppression for an additional 50 days. In addition, grafts
      from this group were then heterotopically retransplanted into isogenic C57BL/6 or
      allogeneic BALB/c recipients to assess their immunogenicity. RESULTS:
      Cyclosporine A-treated mice showed no signs of chronic rejection or priming of
      cellular immunity as measured by proliferation and cytokine secretion in a mixed
      leukocyte reaction. However, there was a notable expansion of memory CD8+ T cells
      specific for donor major histocompatibility complex. When these tracheal
      allografts were retransplanted heterotopically into C57BL/6 or BALB/c, they
      demonstrated reduced responses toward BALB/c and primed responses toward C57BL/6,
      respectively. These results suggest that the grafts express a chimeric phenotype
      consisting of both BALB/c and C57BL/6 antigens. CONCLUSION: These observations
      suggest that long-term withdrawal of immunosuppression does not lead to chronic
      tracheal rejection even in the presence of alloantigen specific cytotoxic T
      lymphocyte responses and that the reepithelialized grafts may contain donor
      elements that impact the generation of immunity.

PMID- 15849537
TI  - Hosts lacking fms-like tyrosine kinase 3 ligand exhibit marked reductions in
      transplant vascular sclerosis.
AB  - BACKGROUND: Mice lacking fms-like tyrosine kinase 3 ligand (Flt3L-/-) as the
      result of targeted gene disruption show severe reductions in dendritic cell (DC)
      subsets. We examined the development of vascular sclerosis and alloimmune
      reactivity in wild-type C57BL/6 (B6) and Flt3L-/- B6 (H2b) recipients of aortic
      allografts from normal BALB/c (H2d) donors. METHODS: DC deficiency was confirmed
      by flow cytometric analysis. Aortic allografts were anastomosed to the infrarenal
      portion of the recipient's abdominal aorta. No immunosuppressive therapy was
      administered. Transplant outcome was assessed 60 days postgrafting by histologic
      and immunohistochemical examination of the grafts. Host reactivity to donor
      alloantigens was determined by assaying splenic T-cell proliferation and T-cell
      infiltration within the grafts, immunoglobulin-G subclass alloantibody levels (by
      flow cytometry), and cytokine production (by enzyme-linked immunosorbent assay or
      graft immunohistochemistry). RESULTS: Sixty days posttransplant, BALB/c
      allografts in wild-type B6 recipients showed severe chronic arteriopathy (intimal
      thickening, alpha-smooth muscle actin+ cell proliferation, fibrosis, and elastic
      lamina disruption). In contrast, profound deficiency of host myeloid, "lymphoid
      related," and pre-plasmacytoid DC subsets was accompanied by marked reductions in
      each feature of chronic rejection. Improvement in graft appearance was associated
      with antigen-specific suppression of ex vivo anti-donor T-cell proliferative
      activity and reductions in interferon-gamma but with enhancement of interleukin
      10 secretion in response to donor alloantigen challenge. CONCLUSION: Permanent
      deficiency of host DC subsets resulting from targeted gene disruption markedly
      inhibits the development of transplant vascular sclerosis, associated with
      striking reductions in both anti-donor T-cell reactivity and immunoglobulin-G
      alloantibody production.

PMID- 15849538
TI  - Tetrahydrobiopterin prevents cyclosporine-induced vasomotor dysfunction.
AB  - BACKGROUND: Cyclosporine A (CsA) is associated with negative side effects such as
      endothelial injury, which may lead to transplant vasculopathy. CsA can impair
      nitric oxide (NO) homeostasis. Therefore, tetrahydrobiopterin (BH4), a NO
      synthase cofactor, may limit endothelial injury by improving NO production. Our
      study examines the effect of CsA and BH4 exposure on endothelial function.
      METHODS: Lewis rats were injected with CsA, BH4, CsA+BH4, or saline
      intraperitoneally daily for 2 weeks. With use of a small vessel myograph,
      thoracic aortic segments were assessed for endothelial-dependent (Edep) and
      independent relaxation after exposure to acetylcholine and sodium nitroprusside.
      Sensitivity to vasospasm was evaluated after exposure to endothelin (ET)-1.
      RESULTS: CsA exposure resulted in impaired Edep vasorelaxation compared with
      control (P=0.01). BH4 attenuated the deleterious effects of CsA. Compared with
      control, all treatment groups demonstrated significantly increased sensitivity to
      ET-1. Furthermore, endothelial nitric oxide synthase expression in the thoracic
      aorta was reduced after CsA treatment, and this reduction was attenuated by BH4
      therapy (P<0.01). ETA receptor expression in the aorta was increased after CsA
      treatment, but BH4 treatment prevented CsA-induced ETA over-expression (P=0.004).
      However, ETB receptor expression was increased by BH4 treatment compared with CsA
      and control (P=0.02). CONCLUSION: Our findings suggest that CsA-induced vasomotor
      dysfunction is a result of alterations in both NO and ET-1 regulation and that
      BH4 may prevent the deleterious effects of CsA. However, the beneficial effects
      of BH4 are associated with increased sensitivity to ET-1. Therefore, a
      combination of BH4 and ET-1 blockade may prove to be an ideal combination for
      preservation of endothelial function.

PMID- 15849539
TI  - Long-term transgene expression and survival of transgene-expressing grafts
      following lentivirus transduction of bone marrow side population cells.
AB  - BACKGROUND: Successful transduction of hematopoietic stem cells is essential if
      gene therapy is to be used clinically to induce immunologic tolerance. METHODS:
      Hoechst 33342 staining was used to isolate a population of bone marrow cells
      enriched for stem cells, termed side population (SP) cells. Murine bone marrow SP
      cells were transduced with HLA-A2.1-expressing VSV-G-pseudotyped lentivirus or
      retrovirus vectors under identical conditions. RESULTS: After transduction
      without prestimulating cytokines, which minimizes cell cycling and helps maintain
      stem cell pluripotency, the HLA-A2.1 gene was found in the DNA of 56% of CFU-GM
      colonies derived from lentivirus-transduced SP cells, but in only 4% of colonies
      derived from retrovirus-transduced SP cells. Lentivirus and retrovirus
      transduction including cytokine prestimulation produced the same degree of
      integration as that following lentivirus-transduction of non-prestimulated cells.
      Transplantation of 5,000 lentivirus-transduced SP cells into lethally irradiated
      mice resulted in long-term expression of the HLA-A2.1 transgene in peripheral
      blood progeny of bone marrow SP cells and prolonged skin graft survival across
      this class I MHC barrier until the time of animal sacrifice. CONCLUSIONS:
      Recombinant lentivirus, but not retrovirus vectors, effectively transduced SP
      cells that were not prestimulated with cytokines and lentivirus-transduced SP
      cells successfully repopulated lethally irradiated C57BL/6 mice, animals where
      there is no selective advantage to repopulation with transduced cells.
      Transplantation of a relatively small number of transduced SP cells led to
      prolonged transgene mRNA expression and antigen-specific survival of grafts
      expressing the foreign MHC transgene.

PMID- 15849540
TI  - Immunologic pathways in a quantitative model of immunosuppression based on
      rejection of an allogeneic or xenogeneic tumor graft.
AB  - BACKGROUND: A quantitative model of immunosuppression was previously developed
      based on the rejection of the allogeneic A/J murine tumor sarcoma 1 (Sa1) in
      immunocompetent mice. Here, the model is used to evaluate the immunologic
      mechanisms of graft rejection and to determine the potential of this model to
      detect synergistic effects of combined immunosuppressive therapies. METHODS: Wild
      type, genetically-deficient, or drug-treated mice were used. Mice were challenged
      subcutaneously with the allogeneic murine tumor cell line, Sa1, or with the
      xenogenic human tumor, MDA435. Tumor growth was monitored with time, with
      increasing tumor size reflecting greater immunosuppression. In some cases, the
      mice were presensitized with either Sa1 or with A/J splenocytes. RESULTS: In
      naive recipient mice, studies in major histocompatibility complex (MHC)-I
      deficient mice and with depleting anti-CD8 monoclonal antibody (mAb) demonstrate
      that CD8 T cells are important for Sa1 rejection. A modest role for perforin but
      not for Fas/Fas ligand could be demonstrated. Blockade of CD4 T cells was more
      effective with decreasing histocompatibility barriers. In contrast, CD4 T cells
      were critical in second-set rejections, but CD8 T cells were not. Rejection of
      xenogeneic tumors was also T-cell dependent as demonstrated by anti-CD3 mAb,
      dependent on both CD4 and CD8 T cells as demonstrated using MHC-I- and MHC-II
      deficient mice, but was more vigorous as demonstrated by the lack of
      effectiveness of immunosuppressive drugs in this model. CONCLUSIONS: This model
      can be used to define dominant and partial effects of immunologic pathways as
      well as synergistic interactions of agents to develop immunosuppressive
      strategies.

PMID- 15849541
TI  - CTLA-4 is important in maintaining long-term survival of cardiac allografts.
AB  - INTRODUCTION: CTLA-4 is a negative regulatory molecule upregulated on activated T
      cells; however, its role in induction and maintenance of transplant tolerance is
      not well understood. METHODS: The characteristics and effects of a novel mouse
      anti-rat CTLA-4 antibody (Ab) (242B58) were examined using fluorescence-activated
      cell sorter, mixed lymphocyte reaction, enzyme-linked immunospot, signaling
      studies, and a rat model of cardiac transplant tolerance induced by
      administration of anti-CD28 Ab and cyclosporine. RESULTS: The anti-CTLA4 Ab was
      shown to bind to CTLA-4 but not prevent subsequent binding of B7 to CTLA-4.
      Binding to CTLA-4 did not result in phosphorylation of early cytoplasmic tyrosine
      kinases, suggesting that this is not a signaling Ab. However, its in vitro
      function was compatible with antagonization of the effects of CTLA-4, thereby
      increasing T-cell proliferation and interferon-gamma production in mixed
      lymphocyte reaction and enzyme-linked immunospot assays, respectively.
      Administration of 242B58 to animals treated with anti-CD28 Ab and cyclosporine
      either at the time of transplantation or various time-points up to 33 days
      posttransplantation did not result in immediate rejection, but rather caused a
      delayed severe acute allograft rejection at approximately 45 days posttransplant.
      CONCLUSIONS: Our results seem to be a reflection of the unique properties of the
      242B58 Ab, which does not antagonize B7 binding to CTLA-4 and affect its ability
      to out-compete CD28 for B7 binding. It does, however, seem to interfere with CTLA
      4 signaling, suggesting that competition for B7 may be important in induction of
      tolerance, but signaling through CTLA-4 is more important in maintaining a
      tolerant phenotype.

PMID- 15849542
TI  - Effects of immunosuppressants on induction of regulatory cells after
      intratracheal delivery of alloantigen.
AB  - BACKGROUND: We previously reported that intratracheal delivery (ITD) of
      alloantigen generated regulatory cells in mice. Here, we examined the effect of
      various doses of conventional immunosuppressants (FK506, cyclosporine A,
      azathioprine, mycophenolate mofetil, and rapamycin) on inducing regulatory cells
      in our model. METHODS: CBA mice (primary recipients) were given C57BL/6
      splenocytes by ITD and either no additional treatment or various doses of an
      immunosuppressant. Seven days later, splenocytes from these mice were adoptively
      transferred into naive secondary CBA recipients that underwent C57BL/6 cardiac
      grafting the same day. RESULTS: Adoptive transfer from primary recipients given
      ITD of splenocytes alone induced prolonged allograft survival in secondary
      recipients (median survival time [MST], 50 days), suggesting that regulatory
      cells were generated. When ITD of alloantigen was combined with daily
      administration of 0.1 mg/kg FK506 or 0.2 mg/kg rapamycin, graft survival was
      similarly prolonged (MST 55 and 50 days, respectively). When combined with 20 or
      40 mg/kg MMF or 0.4 mg/kg rapamycin, the majority of recipients demonstrated
      indefinite survival (MST, >100 days in all groups). When ITD of alloantigen was
      combined with 0.3, 0.5, or 1.0 mg/kg FK506; 5, 10, or 25 mg/kg cyclosporine A; or
      1.0 or 2.0 mg/kg azathioprine, allografts were rejected acutely (MST 7-13 days).
      CONCLUSION: Generation of regulatory cells by ITD of alloantigen was facilitated
      by mycophenolate mofetil and high doses of rapamycin but abrogated by
      cyclosporine A, azathioprine, and high doses of FK506. Low doses of rapamycin and
      of FK506 did not interfere with generation of regulatory cells.

PMID- 15849543
TI  - Effect of renal transplantation on biomarkers of inflammation and oxidative
      stress in end-stage renal disease patients.
AB  - BACKGROUND: Chronic kidney disease patients have a high prevalence of
      inflammation and oxidative stress, and this has been associated with the excess
      cardiovascular morbidity and mortality observed in this population. Because
      maintenance hemodialysis is ineffective in controlling these factors, we
      hypothesized that restoration of kidney function by transplantation would be
      required to improve uremic inflammation and oxidative stress. METHODS: This was a
      prospective cohort study evaluating time-dependent changes in biomarkers of
      inflammation and oxidative stress before and after renal transplantation.
      Nineteen end-stage renal disease (ESRD) patients (age 38.3+/-13.7 years, 58%
      male, 95% white, 21% diabetic) undergoing living-donor renal transplantation were
      enrolled. C-reactive protein (CRP), interleukin (IL)-6, IL-10, tumor necrosis
      factor (TNF)-alpha, protein-associated carbonyl content, and F2-isoprostanes were
      assessed at 1 week pretransplantation and at 1 week and 2 months
      posttransplantation. RESULTS: Pretransplant levels of the pro-inflammatory
      proteins IL-6, TNF-alpha, and CRP, as well as the oxidative stress markers plasma
      protein carbonyls and F2-isoprostanes, were significantly elevated in ESRD
      patients compared with healthy control subjects. We observed rapid and
      significant declines in all of these biomarkers after transplantation that
      persisted for 2 months. CONCLUSIONS: Our findings indicate that restoration of
      renal function by transplantation improves the chronic inflammation and increased
      oxidative stress associated with uremia, which may contribute to the improved
      survival afforded to ESRD patients by renal transplantation.

PMID- 15849544
TI  - Superior vena cava graft for right liver and right lateral sector
      transplantation.
AB  - BACKGROUND: The usefulness of cryopreserved superior vena cava (SVC) grafts for
      venous reconstruction remains to be evaluated in right liver and right lateral
      sector transplantation. METHODS: Reconstruction of the hepatic vein was performed
      when the congested area in the liver graft was significant. A vein graft with a
      suitable shape and length meeting the demands for the venoplasty was selected,
      and SVC grafts were used in 20 recipients. Surgical techniques were classified
      into five types according to the necessity of middle or short hepatic vein
      reconstruction in the liver graft. Surgical outcomes and vein graft patency were
      evaluated. RESULTS: All 20 recipients survived the operation without any
      complications caused by congestion. Liver functions were well recovered in the
      early postoperative period. The 1-year primary patency rates of cryopreserved
      vein grafts used for reconstructed right hepatic veins, inferior right hepatic
      veins, and middle hepatic vein tributaries were 100%, 94%, and 42%, respectively.
      CONCLUSIONS: SVC grafts were feasible for outflow tract reconstruction in right
      liver and right lateral sector transplantation, although the long-term patency of
      the grafts for middle hepatic vein reconstruction remains to be evaluated.

PMID- 15849545
TI  - The effect of 2-gram versus 1-gram concentration controlled mycophenolate mofetil
      on renal transplant outcomes using sirolimus-based calcineurin inhibitor drug
      free immunosuppression.
AB  - BACKGROUND: We performed a sequential study to determine the efficacy and side
      effects of low-dose (1 g) mycophenolate mofetil (MMF) in a CNI drug avoidance
      regimen including sirolimus/steroids. METHODS: A total of 260 kidney-only
      recipients were given basiliximab (232) or thymoglobulin (28) induction, and
      sirolimus/steroids. In addition, 160 recipients were begun on standard MMF 1 g
      twice daily (2-g group), while 100 recipients were begun on low-dose MMF 500 mg
      twice daily (1-g group). The 1-g recipients were concentration controlled to keep
      mycophenolic acid (MPA) C0 levels at 1.8-4 microg/ml. RESULTS: There were no
      statistically significant differences in demographics between the groups. At 6
      months there were no significant differences between the 2-g and 1-g MMF groups
      in patient survival (96.8% vs. 96%), graft survival (92.5% vs. 95%), biopsy
      confirmed and treated acute rejection (8.8% vs. 13%), or mean creatinine mg/dL
      (1.41+/-0.52 vs. 1.47+/-0.67), respectively. Mean MPA C0 levels microg/ml were
      (4.7 vs. 2.3) at 1 month, (4.1 vs. 3.1) at 3 months, and (3.9 vs. 2.4) at 6
      months. There were no significant differences at 1, 3, or 6 months in mean WBC,
      HgB, or platelets, or wound complications. There were significant reductions in
      the number of patients reporting nausea-vomiting-dyspepsia (20.6% vs. 8%,
      P=0.007), diarrhea (34.3% vs. 20%, P=0.01), and abdominal pains (10.6% vs. 4%,
      P=0.05), between the 2-g and 1-g MMF groups, respectively. CONCLUSIONS: The use
      of concentration-controlled 1-g MMF results in comparable transplant outcomes
      with less GI toxicity during the first 6 months posttransplant in a CNI drug-free
      sirolimus based immunosuppressive regimen.

PMID- 15849546
TI  - Mechanisms of hypertension after liver transplantation.
AB  - Hypertension is the most common cardiovascular complication after liver
      transplantation. Systemic vasoconstriction underlies transplant hypertension, but
      the mechanisms contributing to this remain unresolved. Plasma renin, aldosterone,
      and endothelin (ET)-1 together with augmentation index, a measure of arterial
      stiffness, were determined before and at intervals of 1, 3, and 6 months after
      transplant in 32 consecutive patients accepted for liver transplantation. At 3
      months, 47% of patients were hypertensive, and at 6 months, 50% of patients were
      hypertensive. Plasma renin and aldosterone decreased after transplantation but
      were no different between hypertensive and normotensive patients. Plasma ET-1
      levels were elevated pretransplant and decreased at 1 month, but at 6 months,
      levels were elevated in hypertensive patients but not in normotensive patients
      (P=0.019). Augmentation index increased after transplant and was greater in the
      hypertensive patients compared with the normotensive patients (P=0.031). During
      the first 6 months, the renin-aldosterone system does not play a significant role
      in posttransplant hypertension. Elevation in plasma ET-1 and increases in
      arterial stiffness are potential important mechanisms underlying the development
      of hypertension after liver transplant.

PMID- 15849547
TI  - Kidney graft function determines endothelial progenitor cell number in renal
      transplant recipients.
AB  - BACKGROUND: Circulating bone marrow-derived endothelial progenitor cells (EPCs)
      promote vascular repair, and their number correlates with endothelial function
      and cardiovascular risk in humans. In uremic patients, the number of functionally
      active EPCs is reduced. Thus, we assessed EPCs in stable patients 6 months or
      more after renal transplantation. METHODS: We analyzed circulating CD34+
      hematopoietic progenitor cells (HPCs) using flow cytometry and EPCs (in vitro
      assay) in 74 renal transplant patients (51.6+/-11.5 years; 46 males), 74 age
      matched healthy subjects, and 29 patients with preterminal renal failure.
      RESULTS: EPC numbers were similar in renal transplant recipients and controls
      (232+/-92 vs. 250+/-103/high power field; n.s.), but were significantly higher
      than in uremic patients (160+/-97/high power field; P=0.004). In addition,
      transplant recipients had more HPCs than controls (2.71+/-1.65 vs. 1.99+/-1.12
      /microl; P=0.004) and uremic patients (1.64+/-0.96/microl; P=0.001). EPCs in
      renal transplant recipients correlated significantly with graft function(that is,
      Cockcroft-Gault clearance [r=0.294; P=0.012]), but not with age or HPCs.
      Moreover, in the multiple regression analysis, graft function (r=0.332; P=0.01)
      and diastolic blood pressure (r=-0.278; P=0.03) were independent predictors of
      EPCs. In vitro, sera from renal transplant recipients with poor graft function
      significantly inhibited EPC differentiation compared with sera from patients with
      a clearance above 50 mL/min (151+/-54 vs. 274+/-94 EPCs/high power field;
      P=0.02). CONCLUSIONS: EPC numbers in stable renal transplant recipients are
      comparable to those found in healthy subjects. In addition, graft function is a
      significant determinant of EPCs. Prospective studies should explore whether
      improvement of EPCs influences cardiovascular risk in renal transplant
      recipients.

PMID- 15849548
TI  - The absence of delayed graft function is predicted by the presence of manganese
      superoxide dismutase in distal tubules of renal allografts.
AB  - BACKGROUND: Acute tubular necrosis (ATN) in renal allograft biopsies correlates
      poorly with delayed graft function (DGF). Factors involved in the pathogenesis of
      DGF were evaluated in biopsies in an attempt to refine the recognition of DGF.
      METHODS: Anti-cubulin and anti-AE-1/AE-3 antibodies identified proximal and
      distal tubules, respectively. The terminal deoxynucleotide transferase-mediated
      dUTP nick-end labeling technique and active caspase-3 staining were used to
      demonstrate apoptosis. Antibodies against superoxide dismutase (SOD) were used as
      markers of the protective tubular response. Tubular regeneration was evaluated
      using anti-ki 67 and antivimentin antibodies. RESULTS: Of a total of 40 biopsies,
      9 were associated with DGF. ATN was seen in 16 biopsies; 5 were associated with
      DGF. The finding of ATN in the biopsy of a graft predicted DGF in only 56% of
      cases. Absence of distal caspase-3 staining predicted the absence of ATN in 87%
      of cases. The presence of caspase-3 predicted ATN in 54% of cases. The detection
      of manganese-SOD in distal tubules predicts the absence of DGF in 76% of the
      cases. CONCLUSIONS: The use of immunohistochemical staining on posttransplant
      renal biopsies improved its predictive value with respect to ATN and DGF: The
      absence of active caspase-3 in distal tubular epithelium predicts the absence of
      ATN in 87% of cases, whereas its presence predicts ATN in 54% of cases. The
      presence of manganese-SOD in distal tubules predicts the absence of DGF in 76% of
      cases.

PMID- 15849549
TI  - Risk factors for allograft failure in United kingdom renal transplant recipients
      treated with cyclosporine A.
AB  - BACKGROUND: After the introduction of cyclosporine A (CsA), 2-year graft survival
      of transplanted kidneys improved from less than 60% to more than 80%, but long
      term graft survival and graft half-life have shown less change. This study
      investigates the impact of a range of demographic and treatment factors on long
      term graft survival in renal recipients treated with CsA from all renal
      transplant centers in the United Kingdom. METHODS: Data were obtained from the
      Long-Term Efficacy and Safety Surveillance study of renal transplant recipients
      receiving CsA (Neoral; Novartis, Basel, Switzerland). A total of 1,757 de novo
      patients with a functioning graft at 1 year were evaluated. The endpoints
      considered were the need for regular dialysis or death. A stepwise stratified Cox
      model was used to identify the factors associated with outcome. RESULTS: Seven
      independent risk factors for allograft failure were identified: older recipient
      (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.2-2.6), male recipient (HR
      1.8, 95% CI 1.2-2.7), younger donor (HR 1.7, 95% CI 1.2-2.5), above average
      creatinine (HR 1.9, 95% CI 1.3-2.8), chronic allograft nephropathy (HR 7.0, 95%
      CI 4.7-10.4), diabetic recipient (HR 2.2, 95% CI 1.2-4.1), and neoplasm after
      transplant (HR 1.7, 95% CI 1.2-2.6). CONCLUSION: Seven independent risk factors
      were found to influence graft survival. Only two of these can be modified by
      clinical intervention, elevated serum creatinine at 1 year and the occurrence of
      chronic allograft nephropathy. To influence these two factors, the optimization
      of immunosuppressive therapy is essential.

PMID- 15849550
TI  - Thymoglobulin versus ATGAM induction therapy in pediatric kidney transplant
      recipients: a single-center report.
AB  - BACKGROUND: Induction immunosuppressive therapy with the anti-T-cell antibody
      Thymoglobulin decreases the incidence of acute rejection in adult kidney
      transplant (KTx) recipients, but limited data are available for pediatric KTx
      recipients. METHODS: We conducted a historical cohort study to compare rates of
      survival, rejection, and infection in pediatric (age <19 years) KTx recipients
      who received induction therapy with polyclonal antibody, ATGAM (n=127) or
      Thymoglobulin (n=71), from December 1, 1992, to January 31, 2003. Maintenance
      immunosuppression included cyclosporine, azathioprine or mycophenolate mofetil,
      and prednisone. Mean follow-up was 90+/-25 months for ATGAM recipients and 32+/
      15 months for Thymoglobulin recipients. RESULTS: Overall, the incidence of acute
      rejection was lower in Thymoglobulin recipients versus ATGAM recipients (33% vs.
      50%, P=0.02). Epstein-Barr virus (EBV) infection was higher in Thymoglobulin
      recipients versus ATGAM recipients (8% vs. 3%, P=0.002). But the two groups did
      not significantly differ in patient and graft survival rates, incidence of
      chronic rejection, EBV lymphoma, or other infection. CONCLUSIONS: Thus,
      Thymoglobulin induction was associated with a decreased incidence of acute
      rejection and an increased incidence of EBV infection in pediatric KTx
      recipients. EBV monitoring should be performed in EBV-naive recipients receiving
      Thymoglobulin.

PMID- 15849551
TI  - Immunosuppression with cyclosporine A and mycophenolate mofetil after penetrating
      high-risk keratoplasty: a retrospective study.
AB  - BACKGROUND: Graft-prognosis after penetrating high-risk keratoplasty has improved
      considerably with the use of systemic immunosuppressive medications. In this
      retrospective investigation we analyzed the long-term results of 417 high-risk
      keratoplasties with systemic immunosuppression (cyclosporine A [CsA] or
      mycophenolate mofetil [MMF]). METHODS: A total of 417 high-risk keratoplasties
      with postoperative systemic immunosuppression were evaluated retrospectively: CsA
      has been given in 252 keratoplasties since 1987, aiming at blood trough levels of
      120 to 150 ng/mL. Systemic MMF at a daily dose of 2 x 1 g was administered in 149
      surgical procedures. After 16 high-risk keratoplasties, combined systemic
      immunosuppression with CsA and MMF was administered. Systemic immunosuppression
      was scheduled for 6 to 12 months. All patients received fluocortolone 1 mg/kg
      body weight per day, tapered over 3 weeks, and topical prednisolone acetate 1%,
      tapered over 5 months. RESULTS: Rejection-free graft survival after 1 year was
      75% in the CsA group and 89% in the MMF group; 60% of the grafts in the CsA group
      and 72% of the grafts in the MMF group were rejection-free 3 years
      postoperatively (Kaplan-Meier log-rank test P=0.03). Clear graft survival after 1
      and 3 years was 92% and 77% (CsA) and 96% and 87% (MMF), respectively. The MMF
      treated patients showed fewer side effects than the CsA-treated patients. The
      side effects attributable to both drugs were reversible. CONCLUSIONS: We found a
      statistically significant, stronger effect of MMF compared with CsA in preventing
      immune reactions after high-risk keratoplasty, despite a shorter MMF
      administration compared with CsA. Both systemic immunosuppressants were shown to
      have comparable potency regarding clear graft survival and were well tolerated.

PMID- 15849553
TI  - Orthotopic small bowel transplantation in mice.
AB  - On the basis of our experience with rat small bowel transplantation (SBT), we
      established a model of orthotopic SBT in mice. The immediate success rate was
      approximately 50%. Indefinite survival was obtained in the syngeneic group. The
      effect of different immunosuppressive treatments was also investigated: mean
      survival was 10.2+/-1.2 days in untreated mice receiving allogeneic grafts,
      14.2+/-1.6 days with cyclosporine, 24+/-5.1 days in the rapamycin group, and
      73.6+/-29.1 days with tacrolimus-treated animals. From this study, we conclude
      that although the model is technically difficult, it may provide an excellent
      tool to further investigate the physiology and immunology of small-intestinal
      transplantation.

PMID- 15849552
TI  - Donor-specific allograft tolerance by administration of recipient-derived
      immature dendritic cells and suboptimal immunosuppression.
AB  - We recently showed that injection of recipient-type immature bone marrow-derived
      dendritic cells (iBMDCs) the day before transplantation induced a significant
      prolongation of allograft survival. This study aimed at improving the
      administration protocol to induce allograft tolerance. Various amounts of iBMDCs
      were administered to syngeneic LEW.1A rats before and after transplantation of an
      allogeneic LEW.1W heart, with or without additional suboptimal immunosuppression.
      Allograft survival was not improved by repeated injections of syngeneic iBMDCs or
      by additional treatment with low-dose rapamycin. Combining injections of iBMDCs
      and LF 15-0195 showed a striking synergistic effect and induced definitive
      allograft acceptance in 92% of recipients. Tolerant recipients accepted donor
      type, but not third-party type skin grafts, suggesting the development of
      regulatory mechanisms capable of maintaining donor-specific tolerance. The
      reported findings may contribute to the development of new therapeutic strategies
      to induce transplantation tolerance in humans.

PMID- 15849554
TI  - Augmentation of heme oxygenase-1 expression in the graft immediately after
      implantation in adult living-donor liver transplantation.
AB  - Heme oxygenase (HO)-1 is a cytoprotective protein and has recently been
      identified as a graft survival gene. However, there are little data currently
      available regarding the expression of HO-1 in human living-related liver
      transplantation. This is the first report that HO-1 expression is increased in
      small-for-size liver allografts. We performed biopsies of the graft liver and
      donor liver left in six patients at four time points during the procedure and
      studied HO-1 expression by reverse-transcriptase polymerase chain reaction and
      immunohistochemistry. HO-1 mRNA was expressed at a low level in steady-state
      liver tissue but was strongly expressed after perfusion of the graft liver. HO-1
      expression increased in nonparenchymal cells in the human graft liver. The number
      of HO-1 positive cells increased threefold by the end of liver transplantation.
      This study suggests that ischemia-reperfusion injury and excessive shear stress
      secondary to portal hypertension might augment HO-1 expression in the graft
      liver.

PMID- 15849555
TI  - Immunosuppressive therapy with everolimus can be associated with potentially life
      threatening lingual angioedema.
AB  - Everolimus has recently received approval for immunosuppressive therapy in heart
      transplant recipients in Austria and Germany. At our heart center we have treated
      114 patients with everolimus since January 2004. Here we describe 6 cases of
      lingual angioedema (corresponding to 5.3% of the patients). Symptoms occurred
      within 2 to 41 days after initiation of therapy. In 5 out of the 6 patients,
      lingual angioedema disappeared with anti-allergic treatment alone. However, in
      one patient, two severe recurrent episodes of lingual angioedema occurred so that
      therapy had to be discontinued. We conclude that the potentially life-threatening
      condition of lingual angioedema should be considered a severe drug reaction after
      initiation of everolimus therapy in heart transplant recipients.

PMID- 15849556
TI  - Monitoring for polyomavirus BK And JC in urine: comparison of quantitative
      polymerase chain reaction with urine cytology.
AB  - Clinical monitoring for polyomavirus infection is becoming common, but the
      optimal detection technique remains undefined. We compared the relative efficacy
      of exfoliative cytology and polymerase chain reaction (PCR) for detecting viruria
      in 100 urine samples. Definite decoy cells were seen in 8% and probable decoy
      cells in 5% of specimens. PCR showed BK virus (BKV) DNA in all these and in an
      additional 18% of samples. Using decoy cells as a marker of polyomavirus viruria
      cytology has a sensitivity of 41.9% and negative predictive value of 82.8%. The
      specificity and positive predictive value for viruria (not viral nephropathy) are
      100%. False-negative results occurred in samples with suboptimal cellularity,
      vaginal contamination, and a low viral load. One patient with a false-negative
      urine cytology developed BKV nephropathy on follow-up. Compared with PCR, urine
      cytology is a less sensitive technique, which requires morphologically intact
      cells, and cannot distinguish BKV from JC virus.

PMID- 15849557
TI  - Resolution of severe MMF-related gastrointestinal adverse events following
      conversion to enteric-coated mycophenolate sodium.

PMID- 15849558
TI  - Procurement of liver and pancreas allografts in donors with anomalous right
      hepatic arteries.

PMID- 15849559
TI  - Procurement of liver and pancreas allografts in donors with replaced/accessory
      right hepatic arteries.

PMID- 15849562
TI  - Impact of sirolimus on early graft function after deceased-donor kidney
      transplantation.

PMID- 15849563
TI  - Overseas aid.

PMID- 15849573
TI  - Those who can, teach, but who teaches the learners to learn?
AB  - This article was stimulated by Mike Grace's editorial Can those who do--teach? I
      have been an undergraduate and postgraduate teacher for over 30 years and I
      agreed with everything that Mike said about the difficulties of combining doing
      and teaching. The best doers may not make the best teachers and conversely the
      best teachers are not always incapable of doing, whatever some colleagues may
      think to the contrary!

PMID- 15849574
TI  - Tooth preparation for post-retained restorations.
AB  - Failure of root canal treatment and/or post crowns can be avoided in many cases
      if appropriate tooth preparation is carried out. This paper discusses the
      rationale for the timing of post placement following root canal treatment and
      appropriate methods for removal of gutta-percha prior to post space preparation.
      The basic principles of post space preparation are described, which should reduce
      the risk of weakening the root unnecessarily, causing damage to the periodontium
      and post perforation.

PMID- 15849575
TI  - Autoextraction in a child with autistic spectrum disorder.
AB  - Many children with mild/moderate autistic spectrum disorder (ASD) receive care in
      general dental practice. We report a seven year old boy with ASD presenting with
      dental pain who auto-extracted one of his deciduous canines. Children with ASD
      may have hyposensitivity to pain and can exhibit unusual forms of self-injurious
      behaviour.

PMID- 15849576
TI  - Florid cemento-osseous dysplasia in a young Indian woman. A case report.
AB  - We present a rare case of florid cemento-osseous dysplasia (FCOD) occurring in a
      27-year-old Indian woman. She presented with three lesions, two of them
      symmetrical, at the posterior region of the mandible. Another lesion appeared
      nine months later, symmetrical to the existing third lesion. This confirmed the
      diagnosis of florid cemento-osseous dysplasia as being symmetrical asymptomatic
      bone lesions occurring in the jaw. The diagnosis was made radiographically
      depending on a series of radiographs, as biopsy is contraindicated. No treatment
      was required as the lesions were asymptomatic, causing no problem to the patient.
      The patient continues to be reviewed annually. The case is rare in its unusual
      combination of the disease itself (FCOD), age (27 years) and race (Indian).
      Clinical and radiological features are presented.

PMID- 15849583
TI  - Dental priorities.

PMID- 15849584
TI  - Deciduous molars.

PMID- 15849585
TI  - Dental prescribing.

PMID- 15849586
TI  - Contradictory literature.

PMID- 15849587
TI  - Impacts of oral disorders in the United Kingdom and Australia.
AB  - BACKGROUND: Surveys of oral health have not previously compared national adult
      populations using measures of subjective oral health. AIMS: To compare subjective
      oral health of adults in the UK and Australian populations. METHODS: Cross
      sectional studies were conducted of people aged 18+ years in the 1998 UK Adult
      Dental Health Survey and the 1999 Australian National Dental Telephone Interview
      Survey. Subjective oral health was measured using the 14-item Oral Health Impact
      Profile questionnaire (OHIP-14). RESULTS: Among dentate people, the percentage
      reporting impacts 'fairly often' or 'very often' was marginally greater in
      Australia (18.2%, 95% confidence interval (CI) = 16.2-20.2) than the UK (15.9%,
      95%CI = 14.4-17.4). There were larger regional variations in prevalence within
      populations, ranging from 14.8% to 22.3% among Australian states/ territories,
      and from 13.6% to 19.8% among countries within the UK. However, the mean number
      of impacts and rated severity of impacts was significantly greater in Australia
      than the UK. CONCLUSIONS: While the percentage of adults reporting adverse
      impacts of oral health was similar, Australians reported a larger number of
      impacts and more severe impacts than dentate people in the UK. Differences in the
      number and severity of impacts between the two populations may be an artifact of
      different data collection methods or may reflect relatively subtle socio-cultural
      differences in subjective oral health between these populations.

PMID- 15849588
TI  - A retrospective study of periodontal disease severity in smokers and non-smokers.
AB  - BACKGROUND: Smoking has been associated with increased risk of periodontitis. The
      aim of the present study was to compare the periodontal disease severity of adult
      heavy smokers and never-smokers referred for assessment and treatment of chronic
      periodontitis. METHODS: A random sample of patients with at least 20 teeth,
      stratified for smoking and age (5-year blocks, 35 to 55 years), was selected from
      an original referral population of 1,221 subjects with chronic adult
      periodontitis. Adequate records for 59 never-smokers and 44 subjects who smoked
      at least 20 cigarettes per day were retrieved. The percentage of alveolar bone
      support was measured from dental panoramic radiographs with a Schei ruler at x3
      magnification with the examiner unaware of the smoking status. Probing depths at
      six sites per tooth were obtained from the initial consultation. RESULTS: There
      was no significant difference in age between groups. Smokers had fewer teeth
      (p<0.001), fewer shallow pockets (p<0.001) and more deep probing depths
      (p<0.001). The differences were greater in subjects 45 years of age and over. In
      this age group, smokers had approximately 13% more bone loss, 15% more pockets in
      the 4-6 mm category and 7% more pockets in the >/= 7 mm category than the never
      smokers. CONCLUSIONS: This study confirmed that smokers had evidence of more
      severe periodontal disease than never-smokers. The differences increased with age
      confirming an exposure-related response.

PMID- 15849589
TI  - An appraisal of options of the training and education of Professionals
      Complementary to Dentistry.
AB  - The training and education of Professionals Complementary to Dentistry (PCDs) has
      become a topic of close scrutiny and much debate in the recent past, particularly
      with the introduction of enhanced duties and compulsory registration of some
      groups. This paper will describe the background to, the conduct of and the
      findings from a workshop held to explore innovative approaches to the education
      and training of PCDs in the United Kingdom. Existing systems of training and
      education of PCDs will be reviewed through the exploration of published
      literature and through the collection of primary data from interviews with key
      personnel both in the UK and internationally. An option appraisal is described
      which identified the elements common to all training approaches, used the
      elements as the basis for innovative training options, and explored the perceived
      advantages and disadvantages of each option through focus group discussions at a
      one-day workshop. A model for the training and education of PCDs is described
      that maintains existing PCD roles, but offers a broader range of entry points to
      training, settings for training and that builds upon existing skills to
      facilitate progression through the PCD roles.

PMID- 15849590
TI  - Disaster victim identification: Tsunami.
AB  - In the aftermath of the devastating tsunami that hit South East Asia last
      December, a huge operation to try to identify thousands of victims got underway,
      with the help of many overseas medical and dental professionals. British dentist
      Gareth Pearson went to Thailand to try and help in this task and here recounts
      his experience.

PMID- 15849600
TI  - Tooth whitening: facts and fallacies.
AB  - Since the introduction of nightguard vital bleaching (tray bleaching) in 1989,
      dentistry has witnessed an astronomical rise in the interest in tooth
      whitening.(1) As a result, the most frequently asked question is, 'what bleaching
      technique works best?' Virtually all of today's whitening approaches work,
      because bleach is bleach. Whether a nightguard bleach is used with only 10%
      carbamide peroxide (which contains only 3% hydrogen peroxide), over-the-counter
      (OTC) whitening strips are applied containing 6% hydrogen peroxide, or an in
      office bleach is employed using 25-35% hydrogen peroxide, the end results can
      potentially be the same. Similarity of results is possible because the mechanism
      of action is the same: oxidation of organic pigments or chromogens in the tooth.
      Granted, some bleaching approaches are more expeditious than others, owing to
      differences in concentration or exposure time. But as just noted, the most
      important factors in the efficacy of any bleaching treatment are concentration of
      the bleaching agent and duration of the exposure time.

PMID- 15849601
TI  - Latest concepts in root canal treatment.
AB  - This paper highlights one aspect of a presentation to be given at the BDA
      Conference and is written in the context of dentistry in primary care. Careful
      oral health assessment as a foundation to good treatment planning and quality
      dentistry is not new, but there are a number of important new perspectives
      emerging across countries and healthcare systems in terms of the content and role
      of such an assessment in modern dental practice.

PMID- 15849610
TI  - Targeted and restricted complement activation on acrosome-reacted spermatozoa.
AB  - A specific hypoglycosylated isoform of the complement regulator membrane cofactor
      protein (MCP; CD46) is expressed on the inner acrosomal membrane (IAM) of
      spermatozoa. This membrane is exposed after the acrosome reaction, an exocytosis
      event that occurs upon contact with the zona pellucida. We initiated this
      investigation to assess MCP's regulatory function in situ on spermatozoa. Upon
      exposure of human spermatozoa to autologous serum or follicular fluid, we
      unexpectedly observed that acrosome-reacted spermatozoa activated the complement
      cascade efficiently through C3 but not beyond. Using FACS to simultaneously
      evaluate viability, acrosomal status, and complement deposition, we found that
      complement activation was initiated by C-reactive protein (CRP) and was C1q, C2,
      and factor B dependent. This pattern is consistent with engagement of the
      classical pathway followed by amplification through the alternative pathway. C3b
      deposition was targeted to the IAM, where it was cleaved to C3bi. Factor H, and
      not MCP, was the cofactor responsible for C3b cleavage. We propose that this
      localized deposition of complement fragments aids in the fusion process between
      the spermatozoa and egg, in a role akin to that of complement in immune
      adherence. In addition, we speculate that this "targeted and restricted" form of
      complement activation on host cells is a common strategy to handle modified self.

PMID- 15849611
TI  - Slc11a2 is required for intestinal iron absorption and erythropoiesis but
      dispensable in placenta and liver.
AB  - Solute carrier family 11, member 2 (SLC11A2) is the only transmembrane iron
      transporter known to be involved in cellular iron uptake. It is widely expressed
      and has been postulated to play important roles in intestinal iron absorption,
      erythroid iron utilization, hepatic iron accumulation, placental iron transfer,
      and other processes. Previous studies have suggested that other transporters
      might exist, but their physiological significance remained uncertain. To define
      the activities of Slc11a2 in vivo, we inactivated the murine gene that encodes it
      globally and selectively. We found that fetal Slc11a2 is not needed for materno
      fetal iron transfer but that Slc11a2 activity is essential for intestinal non
      heme iron absorption after birth. Slc11a2 is also required for normal hemoglobin
      production during the development of erythroid precursors. However, hepatocytes
      and most other cells must have an alternative, as-yet-unknown, iron uptake
      mechanism. We previously showed that Slc11a2 serves as the primary portal for
      intestinal iron entry in hemochromatosis. However, inactivation of murine Hfe
      ameliorates the phenotype of animals lacking Slc11a2.

PMID- 15849615
TI  - [Partial load after knee and hip total endoprosthesis: impossibility of observing
      their causes and remedies].

PMID- 15849618
TI  - [Is there a cervical headache?].

PMID- 15849619
TI  - [Selected results of a process study about health status of patients with knee or
      hip prosthesis after ambulatory orthopedic rehabilitation].

PMID- 15849621
TI  - [Hip joint surface replacement--a rediscovered procedure for treatment of
      coxarthrosis in a young adult].

PMID- 15849622
TI  - [Mid-term results after subacromial decompression--a comparison of clinical,
      sonographic and radiologic findings].

PMID- 15849623
TI  - [Is vacuum treatment for septic complications of the hip endoprosthesis a
      therapeutic option?].

PMID- 15849625
TI  - [Botulinum toxin A--therapy option in cases of chronic plantar fasciitis?--an
      open treatment attempt with 9 patients and a one year observation period].

PMID- 15849627
TI  - [Minimum requirements for implantation of an artificial hip joint].

PMID- 15849629
TI  - [The unstable upper jump joint after endoprosthesis implantation--revision after
      Castaing's plastic stabilization].

PMID- 15849631
TI  - [Lumiracoxib reduces ulcer complications in comparison to NSAR].

PMID- 15849634
TI  - [Osteoporosis and osteoarthritis--is there really an inverse relation?].
AB  - OBJECTIVE: Increasing bone mineral density (BMD) has been found in several
      studies in patients with osteoarthritis (OA). Therefore, the simultaneous
      occurrence of osteoporosis (OP) and OA is denied by many clinicians. Because of
      our clinical impression, however, we suggest that we have to consider a common
      occurrence. In the present study we have examined the relationship between
      osteoathritis of the knee or the hip and osteoporosis. METHOD: The BMD of the
      lumbar spine and the proximal femur of 117 OA patients (82 postmenopausal female
      patients aged 50-83 and 35 male patients aged 36-86 years) who subsequently
      required hip or knee replacements, but were otherwise healthy, was measured by
      dual-energy X-ray absorptiometry (DXA; Hologic QDR-2000). The results are given
      as required by the WHO and the new German guidelines of the DVO. The BMD was
      measured and categorised in a sex-related manner and the occurrence of disuse
      osteoporosis on the affected limb was examined. Furthermore, a comparison was
      made in the level of BMD between the OA of the involved hip or knee. RESULTS:
      There was a high occurrence of low BMD among the patients. 23.2 % of the women
      were affected by OP. This reflects the normal distribution of OP in the female
      population. 20 % of the male patients had occult OP. This is astonishingly high.
      Osteopenia was measured for 37.1 % of the male patients and 42.7 % of the female
      patients. Age proved to be a significant factor in the degree of BMD. Neither a
      disuse osteoporosis, nor a significance in the OA-affected joint to the degree of
      BMD, could be proven. CONCLUSION: We cannot support the hypotheses that OA
      prevents OP. Moreover, the occurrence of OP in our study reflected the incidence
      of OP in the average female and was astonishingly high in the male population;
      this does not support the hypothesis that the two conditions are mutually
      exclusive. Also a lower risk of fractures among OA patients cannot be concluded.
      There is current open discussion whether a known BMD should influence the
      decision for a cemented or an uncemented prosthesis.

PMID- 15849635
TI  - [Side effects and complications of injection therapy for degenerative spinal
      disorders].
AB  - AIM: The type and frequency of side effects due to treatment of vertebral pain
      syndromes with local injections were examined. Risks and complications were
      evaluated and precautions are presented in order to avoid these problems.
      METHODS: The medical records of 453 patients who had undergone injection therapy
      in hospital for spinal pain syndromes were investigated retrospectively. RESULTS:
      Paravertebral injections with cervical and lumbar spinal nerve analgesia, facet
      joint injections, lumbar epidural-perineural injections, epidural-dorsal and
      epidural-sacral injections, and injections next to the ileosacral joint were
      administered, amounting to a total of 7 963 injections. In 25 cases (0.3 %)
      unfavourable side effects were observed. Epidural-perineural injections led to
      headache in 10 cases and paravertebral lumbar nerve analgesia in 3 cases. Five
      times after epidural-perineural injections circulatory dysregulation with
      vertigo, nausea and decreased blood pressure was observed. One patient fell after
      an epidural-perineural injection, and one patient developed a sensory block up to
      the thoracic segment 6. Five patients showed local allergic reactions at the
      injection site after Mepivacain. All complications could be treated with simple
      symptomatic measures and had no severe effects. CONCLUSION: Compared to other
      studies, only few side effects were observed. The injections described above may
      thus be regarded as low-risk therapy.

PMID- 15849636
TI  - [Extracorporeal single dose and radiographic dosage in image-controlled and
      fluoroscopic navigated pedicle screw implantation].
AB  - AIM: Goal of the current study was to compare radiation dose and fluoroscopy time
      of fluoroscopic computer assisted pedicle screw implantation versus the
      conventional technique. METHOD: For each of 10 specimens two pedicle screws were
      placed using conventional technique (group 1) and two screws were inserted with
      fluoroscopic navigation system (group 2) contralateraly. RESULTS: For
      implantation of two pedicle screws the mean radiation dose was 0.041 mSv in group
      1 and 0.029 mSv in group 2. Fluoroscopy time was 34 seconds in group 1 and 25
      seconds in group 2. The differences of radiation dose and fluoroscopy time for
      group 1 and 2 were statistically significant (radiation dose p = 0.00044,
      fluoroscopy time p = 0.00039). CONCLUSION: We achieved significantly lower
      radiation dose and fluoroscopy time with fluoroscopic computer assisted pedicle
      screw implantation compared with the conventional technique. Concerning exposure
      to radiation for patients and personnel fluoroscopic navigated screw insertion is
      to favour.

PMID- 15849637
TI  - [Residual stability of different interbody fusion techniques after pedicle screw
      loosening].
AB  - INTRODUCTION: In spinal surgery, postoperative failure of pedicle screw
      instrumentation due to loosening of the implant at the bone-screw interface is a
      clinically relevant problem. While there are numerous biomechanical studies
      dealing with stability after internal fixation, little is known about the
      remaining segmental stability after pedicle screw loosening. We hypothesize that,
      in cases of implant loosening, the remaining stability is dependent on whether
      the segment received an isolated pedicle screw instrumentation or a 360 degrees
      instrumentation. METHODS: Motion analysis was performed under static, damage
      free, sagittal strain (preload 100 N) on intact (controls) and posterior
      monosegmental L5/6 destabilized lumbar spines of sheep. Spine preparations
      underwent a flectional torque. Changes of spinal profile were radiographically
      documented, digitalized and then evaluated. Primary insertion of the conical
      pedicle screws was performed with a torque of 1.4 Nm. Pedicle screw loosening was
      simulated by turning the inserted screw back either 180 degrees or 540 degrees .
      Specimens instrumented with screws of differing diameters (5.5 mm and 6.7 mm) as
      well as non-instrumented pedicles were also compared. RESULTS: Independent of the
      type of instrumentation, we found that a loosening of pedicle screws increased
      remaining segmental motion. In maximal flexion (20 degrees ) and loosening of
      pedicle screws by 540 degrees, we found a statistically significant increase of
      remaining segmental motion with sole pedicle instrumentation (- 3.1 degrees ) in
      contrast to 360 degrees instrumentation (- 1.6 degrees ). For extension, a
      significant discrepancy between the two stabilization methods could not be shown.
      In cases where screws were firmly inserted, there was no advantage of using
      pedicle screws with an increased diameter of 6.7 mm. Independent of the type of
      fixation method, 5.5 mm screws that were inserted in widened pedicles showed a
      marked decrease of primary segmental stability. CONCLUSION: This study suggests
      that, concerning the remaining stability, 360 degrees instrumentation is superior
      in cases where pedicle screw loosening has occurred. The screw diameter plays an
      only subordinate role in primary segmental stability when the pedicle screws are
      inserted firmly.

PMID- 15849638
TI  - [Surgical treatment and prognosis factors in spinal metastases of breast cancer].
AB  - AIM: The aim of this study was the evaluation of surgical therapy results and
      prognosis factors in patients with spinal metastases of breast cancer. METHODS:
      55 patients with spinal metastases of breast cancer who were treated surgically
      were retrospectively evaluated. In 11 patients the cervical, in 27 patients the
      thoracic and in 17 patients the lumbar spine was affected. RESULTS:
      Postoperatively, 45 patients (81.8 %) described a reduction in pain and 5
      patients (50 %) reported a neurological improvement. Perioperative complications
      appeared in 27 patients (49.1 %), 2 patients died. For the entire group, the mean
      postoperative survival was 27.2 +/- 28.6 months and the median survival 16.2
      months. In patients with solitary metastasis the univariate analysis did not show
      a significantly longer postoperative survival than in patients with additional
      visceral metastases (p = 0.0659), but patients with solitary metastasis showed a
      significantly longer survival than those with multiple osseous and/or visceral
      metastases (p = 0.0325). In the univariate analysis, the classification of the
      primary tumour, the duration of symptoms, the localisation of the metastases, the
      patient's age and the kind of surgical procedure (posterior stabilising
      instrumentation versus combined posterior-anterior treatment with intralesional
      resection of the affected vertebra and vertebral body replacement) did not show a
      significant influence on the postoperative survival. The multivariate analysis
      did not show a significant prognostic influence for the potentially prognostic
      factors, however, solitary and multiple metastasis showed the highest statistical
      influence for the prognosis (p = 0.1187), followed by the classification of the
      primary tumour (p = 0.1243). CONCLUSION: Pain reduction and neurological
      improvement can be reached by a stabilisation of the diseased spinal region.
      Patients with spinal metastases due to breast cancer showed a relatively long
      postoperative median and mean survival. Therefore, the preoperative evaluation of
      extent of the disease and the therapy concept should be individually adapted. The
      surgical procedure (posterior stabilising instrumentation versus combined
      posterior-anterior approach with vertebrectomy and vertebral body replacement)
      does not significantly influence the survival.

PMID- 15849639
TI  - [Minimally-invasive computer-assisted fluoroscopic navigation for kyphoplasty].
AB  - AIM: The transpedicular placement of a hollow needle into vertebral bodies for
      kyphoplasty requires utmost accuracy and thereby permanent multiplanar X-ray
      control. Facing the increasing number of vertebral compression fractures, the aim
      of this work was the implementation of computer-assistance to optimise the issue.
      Prior to clinical implementation, experimental trials were undertaken to analyse
      the quality-improving options of the technique. METHOD: The virtual image of the
      planning and the puncture were correlated with the postoperative X-ray image of
      the needle. The real canal in the bone was then correlated with the preoperative
      planning in a CT-based 3D model and differences were calculated. As a measure of
      accuracy the deviation of the needle from the ideal intruding vector and the
      distance between its top and the centre of a predefined target were scrutinised
      and related to the indications of the navigation system. Operating time,
      radiation exposure and general applicability were additionally assessed. All data
      were compared with those of a conventional control group. RESULTS: Planning and
      navigation could be executed with high accuracy. With an exactly transpedicular
      approach, neural structures were safely circumnavigated without once missing the
      target. In the control group the distance fault was up to 9 mm. The navigated
      drilling differed from the ideal trajectory by 1 degrees to max. 4 degrees.
      Conventional C-arm control led to a divergence of 4 degrees to 8 degrees .
      Radiation exposure could be reduced through computer assistance by 76 % to a
      fourth of the conventionally resulting amount and the pure operating time thereby
      decreased by 40 %. The inconvenient course of repeated positioning of the C-arm
      was overcome. CONCLUSION: In challenging cases of deteriorated anatomy and
      difficult radiomorphologic orientation, especially of the lower thoracic spine,
      the CAOS-procedure succeeds in finding the optimal pedicular approach to the
      vertebral body, helps to avoid collateral damage and minimises the overall risk
      of the procedure. High accuracy and reduced radiation exposure justify the
      clinical use of fluoroscopic navigation for transpedicular instrumentation.

PMID- 15849640
TI  - [Surgical therapy of unspecific and specific Spondylodiscitis].
AB  - AIM: The aim of this study was to evaluate the clinical and radiological results
      of surgical treatment of thoracic and lumbar vertebral osteomyelitis by means of
      one-stage extrafocal posterior stabilisation, anterior debridement, and anterior
      column reconstruction. METHOD: A retrospective analysis of the peri- and
      postoperative parameters of 62 patients with a clinical and radiographic follow
      up of 2.6 years that were available for 46 patients was performed. In 42 cases,
      the anterior column was restored with structural bone grafts, in 20 patients,
      expandable titanium cages filled with morsellised autologous bone and antibiotic
      collagen sponges were used. To assess the course of spinal alignment a
      radiometric analysis was undertaken. Furthermore, the Roland-Morris score (RMS)
      was applied to evaluate the back pain-related disability. RESULTS: The diagnosis
      was made no earlier than 2.7 months after the first symptoms. Preoperatively, 40
      % of the patients presented with neurological impairment, of these 76 % improved
      after surgery. Staphylococcus aureus was the most common pathogen isolated (32
      %), Mycobacterium tuberculosis was found in 11 % of the patients. Except for one
      patient with revision for persistent infection and consecutive failure of the
      bone graft, primary eradication of the infection was achieved in all cases. At
      follow-up, bony fusion was radiographically observed in all patients. When using
      cages, the segmental loss of correction was significantly lower than when using
      bone grafts (1.0 vs. 4.1 degrees ). At follow-up the RMS averaged 6.6.
      CONCLUSION: One-stage extrafocal posterior stabilisation combined with anterior
      debridement and anterior column reconstruction with bone grafts or titanium cages
      is a safe and effective strategy for patients with vertebral osteomyelitis in
      need of surgery. Titanium cages have proven to be biomechanically advantageous,
      especially in cases of extensive destruction and are not associated with higher
      rates of persistence or recurrence of infection compared to autologous bone
      grafts.

PMID- 15849641
TI  - [Prognosis, surgical therapy and progression in cervical and upper-thoracic tumor
      osteolysis].
AB  - INTRODUCTION: This study analyzes the early and mid-term results of our modular
      rod-screw implant system for the posterior instrumentation of the occipito
      cervical, cervical and cervico-thoracic spine (neon occipito-cervical system,
      Ulrich, Germany) in patients with tumor osteolysis. The prognosis of the patients
      was evaluated using the Tokuhashi score. METHODS: The cervical and upper thoracic
      spines of 14 patients (7 males, 7 females, mean age 61 years, range 40-77 years)
      with osteolysis due to plasmocytoma (n = 2), bronchial (n = 3), mamma (n = 4),
      thyroid (n = 2), esophageal (n = 1) and pancreatic (n = 1) carcinomas as well as
      melanoma (n = 1) were instrumentated between June 2001 and April 2004. RESULTS: A
      stable fixation without loosening or failure of the fixator system was achieved
      in all cases. No impairment of the neurological status was observed. In our
      cohort different prognosis scores failed to make a reliable estimate of the
      expected survival at the time of surgery. CONCLUSION: Posterior instrumentation
      of the cervical spine including the occipito-cervical and the cervico-thoracic
      regions with a modular angle-stable rod-screw implant system (neon) offers good
      stabilization and allows simultaneous decompression. Since tumor masses are
      predominantly located in the anterior portion of the spine, blood loss can be
      controlled well. In this patient collective appears difficult to estimate the
      time of survival by a scoring system.

PMID- 15849642
TI  - [Invasive chondrosarcoma of the thoracic spine as a rare cause of acute
      paraplegia].
AB  - We report on the case of a invasive chondrosarcoma of the thoracic spine in a 65
      year-old woman as a rare cause of acute paraplegia.

PMID- 15849643
TI  - [Results of arthrodesis of the upper ankle joint].
AB  - AIM: This study presents the results of arthrodesis of the ankle in non
      inflammatory osteoarthritic conditions. METHOD: 34 open arthrodeses (33 patients)
      were followed for 5.5 +/- 3.2 years after surgery. At follow-up clinical results
      were evaluated by the Kitaoka and Gruen scores and standing X-rays were analysed
      for the talo-calcaneal angle and the grade of arthrosis. RESULTS: Patients
      expressed high and very high satisfaction in 84 % of the cases; good results were
      higher with the Gruen score (79 %) than with the Kitaoka score (50 %). The
      patients did not complain pain but had some limitation in walking distance; gait
      was compensated in 44 % of the patients. A significant increase of arthrosis in
      adjacent joints could not be observed. A pseudoarthosis was observed in four
      cases and minor, conservatively treated complications arose in seven cases.
      CONCLUSION: We conclude that, on the basis of these results, arthrodesis of the
      ankle still has a place in therapy due to the high patient satisfaction.

PMID- 15849644
TI  - [The potential for training of proprioceptive and coordinative parameters in
      patients with chronic ankle instability].
AB  - AIM: This study was aimed at assessing the outcome of physical therapy based on
      both subjective patient's satisfaction and objective measurement of peroneal
      reaction time in patients with chronic ankle instability. METHOD: 25 patients
      with chronic ankle instability based on functional deficits were included.
      Physical therapy consisted in a 6 weeklong program with muscle strengthening and
      coordination exercises for one hour, three times a week. Before starting physical
      therapy as well as two weeks after finishing the program, patients underwent both
      a clinical exam as well as measurement of their peroneal reaction time. RESULTS:
      Following physical therapy peroneal reaction time of the long (p = 0.0001) and
      short (p = 0.0003) peroneal muscles significantly decreased. Prior to physical
      therapy the Kitaoka score was calculated to be 72.2 (+/- 18.7), the post
      treatment value was 93.3 (+/- 11.7) with a p-value of < 0.001. As for subjective
      patient's assessment on a scale of 1-10 with 1 being the least and 10 the most
      satisfied with therapeutical outcome, patients gave an average post treatment
      score of 8.3 (+/- 1.9). CONCLUSION: Measurement of PRT can be used as a helpful
      diagnostic parameter, as a parameter for quality control and for verification of
      therapy results. Specific physiotherapy leads to good clinical results and
      increased PRT.

PMID- 15849645
TI  - [Pressure distribution after scarf osteotomy for hallux valgus surgery].
AB  - AIM: This study evaluates the pressure distribution, the radiological and
      clinical results in patients before surgery and 6 months after scarf osteotomy
      for hallux valgus. METHODS: 29 patients were examined before surgery and 6 months
      after surgery for symptomatic hallux valgus. Pedographic analysis was performed
      by dividing the footprint of the patients into 8 regions of interest. For each
      region the maximum mean pressure and the peak pressure were evaluated. Moreover,
      clinicofunctional results (AOFAS score) and radiological results were evaluated.
      RESULTS: 6 months postoperatively, maximum mean pressure increased significantly
      under the medial forefoot where as the peak pressure in this region revealed
      indifferent results. Significant improvement of clinicofunctional results and a
      significant reduction of the intermetatarsal and metatarsophalangeal angle could
      be seen. CONCLUSION: These results confirm the clinical and radiological findings
      of other studies, but this study shows for the first time an increase of pressure
      under the first ray of the foot after hallux valgus surgery and an adaptation to
      the pressure distribution of normal feet.

PMID- 15849646
TI  - [Influence of local anesthesia and energy level on the clinical outcome of
      extracorporeal shock wave-treatment of chronic plantar fasciitis].
AB  - BACKGROUND: The efficacy of low energy extracorporeal shock wave treatment (ESWT)
      for chronic plantar fasciitis is discussed controversially. It is unclear whether
      the simultaneous application of local anesthesia (LA) interferes with clinical
      outcome. METHODS: 60 patients with a chronic plantar fasciitis were enrolled in a
      triple-arm (20 patients per group), prospective randomized and observer-blinded
      pilot trial. The patients were randomly assigned to receive either active ESWT
      without LA (;3 x 1 500 shocks, total energy flux density [EFD] per shock 0.09
      mJ/mm(2) [Group A]), ESWT with LA (3 x 1 500 shocks, EFD 0.18 mJ/mm(2) per shock
      [Group B]) or ESWT with LA (3 x 1 500 shocks, EFD 0.09 mJ/mm(2) [Group C]). Main
      outcome measures were: pain during first stepps in the morning (measured on a 0
      10 point visual analogue scale) and number of patients with > 50 % reduction of
      pain and no further therapy needed, measured at 6 weeks after the last ESWT.
      RESULTS: Group A improved in the VAS from 6.4 (SD: 1.7) to 2.2 (SD: 2.6) points,
      group B from 6.7 (SD: 1.5) to 4.1 (SD: 2.4) points, group C from 6.2 (SD: 1.6) to
      3.8 (SD: 2.5) points. A reduction of pain of at least 50 % was achieved in 60 %
      of group A, in 36 % of group B and in 30 % of group C. Group A without LA showed
      a significantly higher improvement in the VAS and subjective evaluation than
      groups B (p = 0.007) and C (p = 0.016). CONCLUSION: At 6 weeks success rates
      after low-energy ESWT with local anesthesia were significantly lower than after
      identical low-energy ESWT without local anesthesia. Higher energy levels could
      not balance the disadvantage of this effect. LA significantly influenced the
      clinical results after low energy ESWT in a negative way. Blinding patients by LA
      in ESWT studies must therefore be considered a systematic error in study design.

PMID- 15849647
TI  - [ How to gauge the importance of sports medicine for the medical training of
      medical students?].
AB  - AIM: Education in sports medicine is offered heterogeneously in German medical
      schools. The self-image of sports has changed from a traditional, competition
      oriented way to adventure, entertainment, wellness and health. Therefore, changes
      of our curricula to a practical-oriented way of teaching are required. In a first
      step the motivations and expectations of the students have to be evaluated.
      METHODS: 90 students enrolled in a sports medicine class were evaluated using a
      questionnaire and compared to 60 students not participating in the sports
      medicine class. RESULTS: The main motivation for the students to sign in was the
      future possibility to subspecialize in sports medicine, followed by interest in
      the subject. The main reasons not to participate were the time factor followed by
      lack of interest. 80 % of the students were regularly practising sports. 66 %
      commented on having been involved in sports trauma. 90 % of the students believe
      that practical-oriented education is absolutely necessary. CONCLUSION: Evaluation
      of the students motivation, knowledge as well as a discussion of the current
      practice to teach sports medicine at medical school confirm the need for
      modification of our curricula to a more practical-oriented education.

PMID- 15849648
TI  - [Comparative study of the treatment of pertrochanteric fractures--trochanteric
      gamma nail vs. proximal femoral nail].
AB  - AIM: We have performed a retrospective comparative study between the trochanteric
      gamma nail (TGN) and the proximal femoral nail (PFN). METHOD: During the period
      1998-2003, 97 TGN and 83 PFN were used for the treatment of pertrochanteric
      fractures. Most of the fractures were of the A3 type according to the AO/ASIF
      classification. Clinical and radiological follow-ups were available for 87 TGN
      and 65 PFN. RESULTS: The mean operative time for the TGN was shorter than that
      for the PFN. Intraoperative complications were noted in 17.5 % and 28.8 % for the
      TGN and PFN groups, respectively. Late complications occurred in 18.4 % for TGN
      compared to 27.6 % of the PFN. Union was achieved in 94.2 % and 89.3 % of the
      patients treated with the TGN and PFN, respectively. The reoperation rates were
      10.3 % and 24.6 % for the TGN and the PFN, respectively. Clinical outcomes were
      good for both groups (65 % in the TGN, 62 % in the PFN group). CONCLUSION:
      Treatment of pertrochanteric fractures using the TGN and PFN implants is quite
      reliable. The major complication was cut-out and occurred mostly in the PFN
      group, while varus deformity was more frequent in the TGN group. The PFN was
      associated with a higher rate of reoperation and longer operative time, probably
      due to a more demanding technique.

PMID- 15849649
TI  - [Diagnostics and treatment of thoracic vascular injuries].

PMID- 15849650
TI  - [Prospective multicenter trial of gastric cancer surgery--a contribution to
      clinical research on quality control].
AB  - By the mean of a prospective multicenter observational study (East German Gastric
      Cancer Study - EGGCS), 1 139 consecutive patients with gastric cancer were
      enrolled in 80 East German surgical departments from January 1 to December 31,
      2002. Out of them, 1,031 (90.5%) underwent surgical intervention. The resection
      rate was 86.4% (n = 891); the R0 resection rate (n = 726) was 81.5%. Gastrectomy
      was performed in 79.8 % (n = 649) of subjects with radical resections (n = 813).
      In approximately 70 % of the interventions with curative intention, lymph node
      resection of the D2 compartment was carried out. The postoperative hospital
      mortality was 8.3%. The results were compared with the data obtained in the
      German Gastric Cancer Study (GGCS 1992); relevant differences and aspects were
      discussed.

PMID- 15849651
TI  - [Resection and reconstruction of the retrohepatic vena cava in combination with
      liver resections].
AB  - Liver resection combined with the resection and reconstruction of the vena cava
      represents the only potential curative therapy for malignant hepatic tumors with
      invasion of the vena cava. We performed a liver resection with segmental
      replacement of the retrohepatic vena cava by synthetic grafts in 29 patients. In
      three cases, the additional presence of central involvement of all three hepatic
      veins required ex situ tumor resection. Four patients underwent a simultaneous
      exstirpation of the primary tumor (kidney or suprarenals). The remaining hepatic
      veins were reimplanted into the graft in three cases, and in two cases the renal
      veins were reimplanted. There was no perioperative mortality. A distal
      arteriovenous fistula was not applied. Five patients revealed postoperative
      transient liver insufficiency, requiring temporary dialysis in three cases. Two
      of these patients developed a transient multiorgan failure with the need of
      mechanical ventilation. 18 patients died during the course of follow-up, 17 of
      these cases due to recurrent metastases of the primary disease. Infection or
      thrombosis of the prosthetic vascular graft have not been observed. Beside tumor
      exstirpation, extended liver resection and concomitant vena cava replacement may
      prevent embolism as well as the obstruction of the vena cava with lower extremity
      swelling and the possibility of developing a Budd Chiari syndrome. We were able
      to achieve a long-term survival for surgically treated patients even in cases
      with advanced tumor stages.

PMID- 15849652
TI  - [Surgical therapy of primary hyperparathyroidism and it's complications.
      Experience with 453 patients].
AB  - 453 patients underwent surgery for primary hyperparathyreoidism between 1994 and
      2003. In all patients, biochemical parameters were monitored and X-ray with USG
      of the neck was done. Struma nodosa was concommitantly present in 48 % of treated
      patients with primary hyperparathyroidism. In such cases, MRI offers better
      resolution of soft tissues. 98.6 % of treated patients had postoperative decrease
      of blood calcium to normal level. 5.4 % of cases were reoperations for primary
      hyperparathyroidism. In 12 % of cases, pathologically changed parathyroid glands
      in dystopic localization were found. In these dystopic localizations, pathologic
      parathyroid glands were found: in 3 % intrathyroid, in 7 % mediastinal and in 2 %
      of all 453 cases in other localization. In 4 % of patients, sternotomy was
      necessary. Persistent hypocalcemia was not registered in any patient. Transient
      hypocalcemia with necessity of infusion therapy was observed in 3.5 % of
      patients. Postoperative hypercalcemia persisted in 1.2 % of patients. Recurrent
      hypercalcemia was present in 0.2 % of cases. In three cases (0.7 %), unilateral
      injury of recurrent laryngeal nerve was observed.

PMID- 15849653
TI  - [Our strategy in the therapy of myasthenia gravis].
AB  - Surgical treatment of myasthenia gravis has at the 3 (rd) Department of Surgery,
      1 (st) Medicine Faculty of Charles University in Prague a multiyear tradition
      which has originated in the 60's of the 20 (th) century. Since that time we
      carried out over 1 000 operations on the thymus, especially thymectomy for
      myasthenia gravis (MG) and with lesser frequency for thymomas. Thymectomy
      combined with exenteration of fatty tissue from the front mediastinum belongs to
      basic MG surgery. According to our experience an optimal approach to the thymus
      is given by partial sternotomy. A jugular approach is not regarded as enough
      radical. Videothoracoscopic approach and operation are possible but take more
      time, however they are the method of choice at some workplaces. The combined
      conservative and surgical treatment brings in 80 % of the cases an obvious
      improvement or deletion of the symptoms of the disease.

PMID- 15849654
TI  - [Our experiences with surgical treatment of iatrogenic colon perforation].
AB  - Coloscopy is a routine examination of high effectiveness. From the surgical point
      of view it has two main risks. The first one is the bleeding after endoluminal
      polypectomy. The other one is the perforation of the gut which is a severe and
      possibly lethal complication. We report on 6 iatrogenic colon perforations and
      its outcome.

PMID- 15849655
TI  - [Surgical therapy in right-sided diverticulitis].
AB  - INTRODUCTION: Left-sided diverticulitis is a common disease in Western countries,
      whereas right-sided diverticultitis is rare and symptoms are often similar to the
      clinical signs of an acute appendicitis. It was the aim of this study to analyse
      surgical experience in right-sided diverticulitis. METHODS: All patients who
      underwent resectional surgery for both right-sided and sigmoid diverticular
      disease were entered prospectively in a registry database (8-year observation
      period, 1996-2003). For the current study, a retrospective analysis of all
      patients who underwent ileocolic resection or right colectomy for right-sided
      colonic diverticulitis was performed, specifically focussing on incidence,
      clinical symptoms, indication for surgery, type of procedure, and
      histopathological parameters including immunohistochemistry, and outcome in right
      sided diverticulitis. RESULTS: Within eight years, 481 patients were treated
      surgically for chronically recurrent or acute complicated diverticular disease:
      468 patients with sigmoid diverticulitis, 12 patients with right-sided
      diverticulitis, and 1 patient with combined right-sided and sigmoid diverticular
      disease. This corresponds to an incidence of right-sided diverticulitis of 2.5 %
      related to the total number of resections for diverticulitis, and an incidence of
      1.3 % in relation to the appendectomies in our patients. In 4 patients, acute
      appendicitis was presumed preoperatively. Most common diagnostic tool was
      ultrasonography. Right colectomy was performed in 9 patients with complicated
      cecal diverticulitis, whereas ileocolic resection was performed in 2 patients and
      simultaneous ileocolic and sigmoid resection was carried out in one patient.
      Postoperatively, no morbidity occurred. Histopathological assessment showed local
      perforation in 75 % (9/12). Hypoganglionosis or aganglionosis was detected in 5
      of 12 resected specimen. DISCUSSION: As right-sided diverticulitis is a rare
      colonic disease in Western countries, the differentiation from acute appendicitis
      can be difficult. In general, there is no difference in the treatment of right
      sided diverticulitis compared to left-sided diverticulitis, and surgery is only
      indicated in complicated right-sided diverticulitis. Resection of the inflamed
      colon with primary anastomosis is safe and can be performed by laparoscopy in
      experienced centers. At present, it can only be speculated whether
      hypoganglionosis or aganglionosis are causative factors in the etiology of right
      sided diverticulitis.

PMID- 15849656
TI  - [The importance of measuring intraabdominal pressure in cases of severe acute
      pancreatitis].
AB  - AIM: Evaluating the importance of intraabdominal pressure measurement in cases of
      severe acute pancreatitis and its use in determining indication for surgery.
      METHODS: A retrospective evaluation of the treatment of patients with severe
      acute pancreatitis hospitalised at the Department of Surgery or the Department of
      Anaesthesiology and Resuscitation of the Charles University hospital in Pilsen
      during the last two years (from January 1 (st), 2002 to December 31 (st), 2003)
      was performed. RESULTS: During this period, 63 patients with severe acute
      pancreatitis were hospitalised at both departments, among which 18 patients
      underwent an operation (28.6 %), eight of them died (12.7 %). In four of the 18
      patients who underwent an operation the surgery was indicated due to progression
      of abdominal compartment syndrome (ACS) and all of these patients survived.
      CONCLUSIONS: At present, basic treatment of severe acute pancreatitis is
      considered to be conservative. The only generally accepted indication for surgery
      is an established infection of the necrotic tissue. In our presentation, we draw
      attention to those cases where the general condition of the patient deteriorates
      combined with a progression of ACS and where a decompressive laparotomy can
      improve the prognosis of the disease.

PMID- 15849657
TI  - [Combined pancreas kidney transplantation after isolated kidney transplantation].
AB  - Simultaneous pancreas kidney transplantation (SPK) is an established therapy for
      type 1 diabetics with end stage or preterminal renal disease. SPK is superior to
      isolated kidney transplantation (KTX) in diabetic patients. Even pancreas-re
      transplantations are more common in these patients now, mostly after SPK. But
      Experience with SPK after KTX is rare. Between 1994 and 2003 six Re-SPK 4.5 to
      8.5 years after KTX were performed in our department. Average age of the
      recipients was 40.5 years. They had been suffering from diabetes for an average
      of 29.3 years. Four recipients were on dialysis again, whereas two had
      preterminal renal insufficiency. Pancreas transplants were drained through the
      bladder (n = 1) or into the small intestine (n = 5) with systemic venous
      anastomosis. After a median observation period of 28 months (8 to 99 months) all
      six recipients are insulin free. One patient lost his kidney graft due to severe
      acute rejection. Therefore kidney graft survival is 83 %. Four acute rejections
      (66 %) were observed in 4 patients. Only one rejection was treated successfully
      by steroids. Two rejections could be stopped with antibodies. 3 patients had
      infections in the early postoperative period (sinusitis, urinary tract infection,
      wound infection). Even after KTX with graft failure, diabetic patients suffering
      from renal disease can be re-transplanted successfully with SPK.

PMID- 15849658
TI  - [Open versus laparoscopic operation for perforated appendicitis--a comparative
      study].
AB  - INTRODUCTION: Laparoscopic therapy of complicated appendicitis is still discussed
      controversially. This retrospective study compared the clinical results of open
      and laparoscopic appendectomy in a single centre. PATIENTS AND METHODS: Within a
      period of three years (1999 to 2001) 493 patients with suspected acute
      appendicitis were operated prospectively at a German district hospital (250 open
      appendectomies, 243 laparoscopic appendectomies). Twenty percent of the patients
      in every group had a complicated appendicitis (48 open, 44 laparoscopic
      appendectomies) and were analysed retrospectively considering demographic data,
      operative time, body mass index, preoperative inflammatory parameters (white
      blood cell count, C-reactive protein and body temperature) and postoperative
      complication rate. RESULTS: Both groups were comparable with regard to
      demographic data. One patient of the laparoscopic group needed an open operation
      (conversion rate 2.3 %). The body mass index of the laparoscopic group was
      significantly higher (26.3 vs. 24.1 kg/m(2)). Preoperative white blood cell
      count, C-reactive protein, body temperature as well as postoperative antibiotic
      therapy and analgesics requirement were comparable in both groups. There was no
      significant difference between the length of operative time (open 48 min,
      laparoscopic 53.5 min). The postoperative hospital stay was significantly shorter
      in the laparoscopic group (8 vs. 9 days, p = 0.032). Complication rate was
      significantly lower in the laparoscopic group (11.5 vs. 35 %, p = 0.014).
      CONCLUSION: Laparoscopic appendectomy is a safe procedure for the treatment of
      complicated appendicitis with a significantly decreased complication rate and
      shorter postoperative stay.

PMID- 15849659
TI  - [Change of daily life activity after femoral hip fracture in elderly patients].
AB  - Hospital mortality after hip fracture in elderly patients has decreased
      significantly in previous years. However, patients often show reduction of daily
      life activity. The aim of the following study was to assess clinical and
      radiological results nine months after operation of hip fracture. A total of 127
      patients (mean age 77.2 years) were stabilized by arthroplasty because of femoral
      neck fractures or by gamma locking nail because of trochanteric fractures.
      Modified Harris-Hip-Score as well as social situation at time of follow-up
      compared to pretrauma situation were evaluated. Hospital mortality was 3.2
      percent. Follow-up could be performed in 78 patients clinically and
      radiologically by examination in the hospital. At time of follow-up 19.7 percent
      of patients had already died independent of the operative procedure. Only 65
      percent of patients were able to live at home. Modified Harris-Hip-Score at
      follow-up was decreased significantly by 16 points compared to the situation
      before the trauma. The reduction of the score was caused mainly by deterioration
      of hip function and less by femoral or hip pain. In future the main scope after
      hip fracture must be an improvement of rehabilitation of elderly patients.

PMID- 15849660
TI  - [Osteosynthesis of ipsilateral hip and femoral shaft fractures with the PFN
      long].
AB  - AIM: The paper retrospectively evaluates a set of patients with ipsilateral
      fractures of the proximal femur and shaft treated with PFN-long. MATERIAL: 19
      patients (14 males and 5 females), aged 48 in average, were treated from 1998
      2003. The fractures included 2 types: combined intraarticular femoral neck and
      shaft fractures: 8 cases, and 11 cases of complex extraarticular proximal femoral
      fractures and its shaft. RESULTS: A total of 17 patients followed up for at least
      12 months was evaluated according to the Sanders and Regazzoni scoring scale.
      Bone union resulted in all patients. This was accomplished within 6 months in 10
      patients (59 %), 9 months in 16 patients (94 %), and one patient healed within 12
      months. Excellent results were achieved in 59 %, good results in 35 % and a
      satisfactory result in 6 %. We have recorded 3 cases of postoperative
      complications (16 %). These complications were all due to imperfect reduction.
      Early complications included a wound haematoma with necessary operative revision.
      Late complications, such as delayed healing, were resolved by reoperation in 1
      case. CONCLUSION: Long PFN is a quality implant which extends our options in the
      treatment of ipsilateral hip and femoral shaft fractures. It is one of the most
      beneficial implants in the category of reconstruction nails. The availability of
      only 3 nail lengths and 1 diameter presents a certain drawback.

PMID- 15849661
TI  - [Experiences with the Butler procedure for overlapping fifth toe].
AB  - Overlapping fifth toe is a finding in pediatric orthopaedics which rarely
      requires operative therapy. PATIENTS AND METHOD: Between Jan. 1, 1992 and Dec.
      31, 2002 five operations of an overlapping fifth toe using the Butler procedure
      were performed at a mean patients age of 5.5 years (min: 3, max: 9). All patients
      were clinically evaluated after a mean follow-up of 6 years (min: 2, max: 10)
      according to the score of Black. We present the technique of the Butler procedure
      and discuss the relevant literature. RESULTS: An excellent result was achieved in
      all patients. Despite the extensive soft tissue release no complications could be
      found. CONCLUSION: The Butler procedure is a simple and safe procedure without
      any need of immobilisation.

PMID- 15849662
TI  - [Reconstructive surgery using an artificial dermis (Integra): results with 19
      grafts].
AB  - BACKGROUND: Integra was initially developed for covering of acute burn wounds.
      The artificial dermis is a bilayered dermal substitute, the upper layer is a thin
      silicone layer, which acts as temporary epidermis, the under layer is a collagen
      network, which functions as the dermis. In the meantime, Integra is applicated in
      reconstructive surgery. PATIENTS AND METHODS: We present a series of 12 patients
      who underwent reconstructive surgery with Integra grafting for a total of 19
      operational sites. The average area grafted per procedure was 210 cm(2) (15-1 200
      cm(2)). The operation sites were located at the extremities, trunk and head-neck.
      The split thickness skin graft was performed, on average, after 20 days (16-29
      days). The patients were admitted for 41 days on average (24 days-3 months). The
      follow-up was after 17 months (9-30 months). RESULTS: Early complications
      included seroma, loss of Intregra, and infection. Late complications were
      instable scars. In five cases, we found slight hypertrophe scars in borderline
      between healthy skin and covering with Integra. CONCLUSION: The advantages of
      using Integra in reconstructive surgery are its immediate availability and the
      availability in large quantities. Disadvantages are the necessity of two
      operations, risks of infection, the high price and time-consuming dressing
      changes. Defect covering with Integra should be used in special cases.

PMID- 15849663
TI  - [Serious complications of injections--retrospective analysis of incidences,
      complication-management, prophylaxis and economic aspects].
AB  - The parenteral drug application is a routinely used method in all medical
      disciplines. Intramuscular, intraarticular, intravenous injections and infusions
      can cause local complications such as abscesses, articular infections or
      paravasates. These local complications can lead to bacteraemia, sepsis and may
      lead to multiple organ failure associated with high morbidity and mortality.
      Although these complications are rare, they are sometimes disastrous and result
      in life threatening clinical conditions. During a retrospective analysis (review
      period 1998-2002) 24 patients were admitted and hospitalized in our department.
      Within this report we demonstrate 7 patients with fatal complications after
      injections. In the majority of cases minor patients' complaints were proceeding
      before major complications were present. A long and expensive treatment period
      with multiple surgical interventions ends up in functional disabilities and
      unsatisfactory aesthetic results. Instead of delayed surgical treatment immediate
      radical surgical care is crucial to prevent disastrous complications. In case of
      the inability of sufficient debridement, amputations are sometimes indicated in
      the sense of "life before limb". Besides the consequences for the patient these
      disastrous complications have a high socioeconomic impact and result in reduced
      reimbursement for the hospital stay.

PMID- 15849664
TI  - [Angiographic embolization of seriously bleeding vessels as an emergency
      procedure after traumatic disruption of the symphysis].
AB  - Bleeding after instable fractures of the pelvic ring results in a mortality-rate
      of 7-21 percent. A 65-year-old male patient who fell from his horse and sustained
      an open book injury with disruption of the symphysis and iliosacral joint
      developed a dangerous haemorrhagic shock situation in the emergency room. A
      computer tomography with contrast medium was performed immediately. The outflow
      of contrast medium behind the symphysis indicated an acute arterial bleeding. An
      angiography revealed a bleeding from both Aa. obturatoriae and the right A.
      epigastrica inferior. The difficulty to stop the bleeding surgically resulted in
      the decision to embolize the vessels angiographically. This procedure terminated
      the acute bleeding and haemorrhagic shock situation immediately. The pelvic ring
      disruption was stabilized by internal fixation ten days later. The patient had an
      uncomplicated course.

PMID- 15849665
TI  - [Haemosuccus pancreaticus].
AB  - Haemosuccus pancreaticus is a rare cause of gastrointestinal bleeding. The blood
      is passing into the pancreatic duct through the route between an aneurysm of an
      artery close to the pancreas and pancreatic duct. The blood goes to the
      gastrointestinal system through Vater's papilla and the patient becomes anemic.
      The authors describe their own clinical observations. In the presented paper the
      pathogenesis of the disease as well as difficulties of diagnosis are discussed.
      The possible ways of treatment are mentioned, too. It is necessary to consider
      haemosuccus pancreaticus in patients with proved chronic pancreatitis and in
      patients with ethylic anamnesis. Duodenoscopy, ERCP and especially angiography
      help to set the diagnosis. For the treatment it is recommended to perform the
      embolization of the bleeding artery or an operation such as pancreas resection,
      artery ligation or alternatively a drainage operation.

PMID- 15849666
TI  - [Appendiceal mucocele causing pseudomyxoma peritonei].
AB  - The authors present the case of a very rare pseudomyxoma peritonei as a late
      complication of appendectomy. The definite diagnosis was established 11 years
      after appendectomy for appendiceal mucocele. In the paper the authors emphasize
      the need for correct retrospective evaluation of all data in patients with
      unusual diagnoses.

PMID- 15849670
TI  - [The knowledge, clinical control and attitudes of Primary Care physicians when
      dealing with epileptic patients. Preliminary findings].
AB  - INTRODUCTION: Epilepsy is a common disease with important social and economic
      repercussions. Patients with epilepsy have traditionally been discriminated by
      both the general population and physicians. A physician's lack of knowledge about
      epilepsy could be the cause of an incorrect clinical control (CC). AIMS: The
      purpose of this study is to examine the origins of the knowledge, the CC and the
      attitudes of physicians in Tenerife with respect to the treatment of patients
      with epilepsy. MATERIALS AND METHODS: In January 2003, all Primary Care
      physicians in Tenerife were given a questionnaire that asked them about their
      knowledge, CC and attitudes when dealing with cases of epilepsy. Of the 260
      surveys initially sent out, 182 were returned. RESULTS: The questionnaire was
      answered by 70% of doctors, of which 34 were paediatricians and 148 were general
      practitioners, with no differences between sexes. Most physicians acquire their
      knowledge, observe and treat their first seizure in the Faculty and during their
      period of hospital residency. 44% of them are barely or not at all satisfied with
      their knowledge on the subject. The most highly valued therapists are
      neurologists and neuropaediatricians. The goal that is sought is to eliminate the
      impact of the disease on the patient's quality of life. They rarely establish or
      modify antiepileptic treatment and state that they have doubts about
      neuropsychological disorders and integrating patients with epilepsy in the
      workplace. CONCLUSIONS: The physicians in Tenerife define themselves as
      professionals with scant knowledge about epilepsy and feel they are poorly
      qualified to treat patients with the disease, who are usually referred to
      specialists in Neurology.

PMID- 15849667
TI  - A genomewide exploration suggests a new candidate gene at chromosome 11q23 as the
      major determinant of plasma homocysteine levels: results from the GAIT project.
AB  - Homocysteine (Hcy) plasma level is an independent risk marker for venous
      thrombosis, myocardial infarction, stroke, congestive heart failure, osteoporotic
      fractures, and Alzheimer disease. Hcy levels are determined by the interaction of
      genetic and environmental factors. The genetic basis is still poorly understood,
      since only the MTHFR 677 C-->T polymorphism has been consistently associated with
      plasma Hcy levels. We conducted a genomewide linkage scan for genes affecting
      variation in plasma Hcy levels in 398 subjects from 21 extended Spanish families.
      A variance-components linkage method was used to analyze the data. The strongest
      linkage signal (LOD score of 3.01; genomewide P = .035) was found on chromosome
      11q23, near marker D11S908, where a candidate gene involved in the metabolism of
      Hcy (the nicotinamide N-methyltransferase gene [NNMT]) is mapped. Haplotype
      analyses of 10 single-nucleotide polymorphisms within this gene found one
      haplotype associated with plasma Hcy levels (P = .0003). Our results, to our
      knowledge, represent the first genomic scan for quantitative variation in Hcy
      plasma levels. They strongly suggest that the NNMT gene could be a major genetic
      determinant of plasma Hcy levels in Spanish families. Since this gene encodes an
      enzyme involved in Hcy synthesis, this finding would be consistent with known
      biochemical pathways. These data could be relevant in determining the
      relationships between Hcy level, cardiovascular disease, osteoporosis, and
      Alzheimer disease.

PMID- 15849671
TI  - [Seasonal variations in the outbreaks in patients with multiple sclerosis].
AB  - INTRODUCTION: It has been suggested that there is an environmental factor at play
      in the aetiology and pathogenesis of multiple sclerosis (MS) that acts as an
      essential component of the disease process, and a number of studies also point to
      a relationship between the seasons of the year and the appearance of outbreaks.
      AIMS: Our aim was to study the possible relation between seasonal variations and
      the appearance of outbreaks in patients with relapsing-remitting forms of MS.
      PATIENTS AND METHODS: We studied 31 patients over the period between 1997 and
      2002 and calculated the monthly and quarterly rate of incidence of outbreaks. The
      statistical evaluation of the results was performed by applying the Chi-squared
      test. RESULTS: We observed a higher incidence of outbreaks in the summer months
      (more in June) and a lower incidence in winter (less in December), with
      statistically significant differences. CONCLUSIONS: In our patients, outbreaks of
      MS are related to seasonal variations, with a higher number in the warmer months
      and fewer in the colder months.

PMID- 15849672
TI  - [Evaluation of the higher brain functions in 1st and 7th grade schoolchildren
      belonging to two different socioeconomic groups].
AB  - INTRODUCTION: The higher brain functions, together with the devices that sustain
      them, are essential assets belonging to human beings which are used to situate
      themselves in the world. They can be studied by conducting neuropsychological
      tests, the results of which vary according to demographic factors, such as age,
      sex, hand dominance, culture and level of schooling. The socioeconomic level
      (SEL) is another factor to be taken into account and must also be evaluated.
      AIMS: Our objective was to evaluate and analyse the influence of SEL on the
      results obtained from neuropsychological tests carried out in normal school-age
      children. SUBJECTS AND METHODS: We studied 401 normal children, of both sexes,
      taken at random, at the beginning (1st grade, 6 years old) and at the end (7th
      grade, 12 years old) of elementary school and belonging to two different SEL:
      high and low. Schools belonging to different categories were selected: public,
      private, urban and suburban. A battery of tests that is commonly used in
      Neuropsychology was utilised to evaluate laterality, spatial orientation,
      integration (Bender's test and the Rey figure test), attention, memory and the
      areas of language, gnosis and praxis. RESULTS: Significant differences were found
      in relation to the SEL in the 1st and 7th grade tests: 20/27 (74%) and 17/27
      (62%), respectively. These always meant lower results in the low SEL, except body
      scheme, ideomotor praxis and phonological coding, which in the 7th grade run in
      the opposite direction. Results were not related to the type of school (urban
      suburban, public-private), sex, laterality or teachers' characteristics.
      Differences were more striking in the area of language, basic devices (attention,
      memory) and in the tests that integrate several different functions (Bender's
      test, Rey figure test). CONCLUSIONS: SEL is linked to the results obtained in
      neuropsychological evaluation tests. There is a direct relationship with low
      results in the low level. There is also a correlation between certain family
      characteristics associated to the SEL and the scores in the cognitive evaluation
      tests.

PMID- 15849673
TI  - [The cost of cerebrovascular accident].
AB  - INTRODUCTION AND AIM: One out of three persons will die of cerebrovascular
      accident (CVA), another one will be disabled, and the third one will recover.
      This research has been taken to estimate the costs of CVA in the Basque Country.
      MATERIALS AND METHODS: The cost of illness is studied from a societal
      perspective. It is based on the prevalence of the disease. Population costs has
      been estimated from the use of resources of a randomized sample of patients
      admitted to hospital with stroke during the year 2000, and followed for 12
      months. Transitions costs (those that happen just once) and state costs (those
      remaining in patients lifetime) have been studied separately. RESULTS: The
      prevalence of CVA was 1.780 x 10(5). Average transition cost per patient was
      4,762 euros and average state cost for patient/year was 10,506 euros. The
      estimated cost for the Basque Country is 120,249,986 euros in the year 2000.
      Transition costs were 16,460,729 euros and state costs 103,789,257 euros in the
      same year. State costs were due to disability. CONCLUSIONS: The analysis of the
      costs of CVA from a societal perspective gets us to the heart of illness causing
      disability, the social costs of CVA are 74.3% of the total cost.

PMID- 15849674
TI  - [Ergotism. A case report and review of the literature].
AB  - INTRODUCTION: Ergotism is characterised by an intensive generalised
      vasoconstriction of small and large blood vessels. The symptoms derive from the
      regional ischemia caused by the vasospasm produced by ergotamine. Nowadays,
      ergotism is almost exclusively due to the excessive ingestion of ergotamine
      tartrate used in the treatment of migraine. The main treatment consists in
      withdrawing the medication. CASE REPORT: Our study involves a 53-year-old male
      with a history of migraine since his youth, who was treated with ergotaminic
      preparations up until the day before admission to hospital. He was admitted
      because of a 7-day history of symptoms including bilateral and symmetrical
      anaesthesia of the fingers and a general feeling of weakness, associated with
      intense pain and cyanosis of the right thenar eminence. On admission, it was not
      possible to measure his AT in the upper limbs and his peripheral pulses dropped
      in a generalised manner. Aetiologies involving vasculitis were ruled out. An
      angiography study showed segmented stenosis of arteries in the upper and lower
      limbs. Ergotaminic agents were withdrawn and nifedipine was indicated. The
      symptoms disappeared, the physical examination was normal and results of a
      control angiography study were also normal. CONCLUSIONS: Ergotamine intoxication
      can be detected by a thorough interview and physical examination; it should be
      suspected when faced with symptoms that are compatible with vasospasms and a
      history of ingestion of the drug, in the absence of any prothrombotic, liver,
      kidney or vasculitic pathology. This condition is treated by withdrawing the drug
      and administration of vasodilators if the symptoms are intense. In this paper, we
      review the history, pathophysiology, initial symptoms and signs, diagnosis and
      treatment of ergotamine poisoning.

PMID- 15849675
TI  - [Epilepsy, cerebral calcifications and coeliac disease. The importance of an
      early diagnosis].
AB  - INTRODUCTION: Coeliac disease (CD) has been linked to several neurological
      disorders, with a clearly higher incidence of epilepsy than in the general
      population. Since Gobbi's original description of the epilepsy with cerebral
      calcifications and coeliac disease syndrome in 1992, various reports have been
      published concerning different stages of development, although a number of
      questions remain to be answered with respect to its pathogenesis. The aim of this
      study is to describe the clinical symptoms and progression of three patients with
      the characteristic syndrome, who were diagnosed in the early stages of the
      disease. CASE REPORTS: We describe the cases of three males, of school age, who
      visited because of partial seizures with visual symptoms that were secondarily
      generalised. A tomography scan of the head revealed bilateral occipital
      calcifications in all cases. The electroencephalogram showed temporooccipital
      paroxysmal discharges with a normal background rhythm. Tests for antiendomysium
      and antigliadin antibodies, with positive results, and a small intestine biopsy
      study were requested, which confirmed the suspicion of a grade 3 severe
      enteropathy. All the patients, following a gluten-free diet and taking
      anticonvulsants, were free of seizures in the follow-up (1, 2 and 8 years).
      CONCLUSIONS: It is of vital importance to investigate CD in any patient with
      epilepsy and occipital cerebral calcifications, even in the absence of digestive
      symptoms, since early diagnosis and treatment with exclusion of gluten affect how
      the syndrome courses later on.

PMID- 15849676
TI  - [Mumps meningitis: a case mix in a Neurology Department].
AB  - INTRODUCTION: Parotiditis is a viral infection that produces a non-suppurative
      inflammation of the parotid glands, although it may affect other salivary glands,
      the testicles, meninges and the pancreas. Clinical meningitis appears in 1-10% of
      cases, normally between the 4th and the 10th day after infection of the parotid
      glands. In this study, we analyse the clinical and analytic characteristics of
      the patients admitted to our Neurology Department over the last 12 years. CASE
      REPORTS: A retrospective study was conducted by analysing the hospital discharge
      reports. The eligibility criterion was the existence of an acute meningeal
      syndrome linked to the presence of positive IgM titres for the parotiditis virus.
      In all, 13 cases were found, with a mean age of 16.5 years, and most of them were
      males (92.3%). Parotiditis preceded meningitis in all our patients with an
      average of 8.3 days, while orchiepididymitis, when it occurred, appeared at the
      same time or after meningitis. Analysis of the cerebrospinal fluid showed a
      lymphocyte profile with glycorrhachia above 40%, except in two cases that showed
      a non-persistent neutrophilic profile. There was a transient 30.7% reduction in
      prothrombin time in the patients. No sequelae were observed. CONCLUSIONS:
      Vaccination campaigns have drastically reduced the number of cases of meningitis
      due to this germ since the second half of the 90s. This virus must be borne in
      mind in cases of meningitis in young males who come from underdeveloped
      countries.

PMID- 15849677
TI  - [The evolution of sleep: birds at the crossroads between mammals and reptiles].
AB  - INTRODUCTION: The evolution of sleep is one of the mysteries surrounding the
      sleep. Since the discovery of the two phases in the mammalian sleep, NREM and
      REM, the sleep researchers have unsuccessfully tried to understand their origin
      and the causes of the sleep duality. Looking for an answer to these questions,
      the sleep of reptiles (the parental group of mammals) and birds (also descending
      from reptiles) has been studied. As a result, NREM and REM were found in birds
      but not in reptiles, and the question remains thus unresolved. DEVELOPMENT AND
      CONCLUSIONS: This review presents a critical analysis of the published sleep
      studies developed in birds and points to a possible cause of the conflict:
      considerable doubts can be cast on the existence of the two sleep phases in
      birds. If birds turn to have only one sleep phase, they would have a very similar
      sleep to that of reptiles. As a consequence, the two phases, REM and NREM, would
      be exclusive of mammals, and both would have appeared as a consequence of the
      evolutionary changes in the development of the brain from reptiles to mammals.

PMID- 15849678
TI  - [Neurodevelopmental (fragile X syndrome) and neurodegenerative (tremor/ataxia
      syndrome) disorders associated to the 'growth' of a gene].
AB  - AIM: To present the latest findings on fragile X syndrome, the first genetic
      disorder identified to be caused by a new type of mutation called trinucleotide
      repeat expansion. DEVELOPMENT: Fragile X syndrome is the most common form of
      inherited mental retardation, is caused by hyperexpansion and hypermethylation of
      a CGG repeat tract in the FMR1 gene. In the first section we will discuss the
      various aspects of the gene mutation and the gene product, its phenotypic
      consequences in mutation carriers, diagnostic methodology, epidemiology,
      prevention, treatment and situation in Costa Rica. The second section deals with
      the recent findings in relation to the very recently described fragile X
      premutation tremor/ataxia syndrome, a neurodegenerative disorder affecting
      carriers of the mutation. CONCLUSIONS: Screening for the gene premutation in aged
      individuals who have tremor and balance problems is important, especially when
      accompanied by other signs such as parkinsonism, short term memory loss and
      dementia. Family genetic counselling can help those affected as well as future
      generations which may inherit fragile X syndrome.

PMID- 15849679
TI  - [Nitric oxide in malignant astrocytes].
AB  - INTRODUCTION: One of the different molecules involved in the development of
      astrocytomas is nitric oxide (NO), a gaseous radical that, depending on the cell
      type and the experimental paradigm selected in the pathology, can play either a
      cytotoxic or a cytoprotective role. DEVELOPMENT: During the development of an
      astrocytoma NO acts as a tumouricidal agent, although it can also alter vascular
      reactivity and lead to neovascularisation, thereby contributing to the invasive
      capacity (aggressiveness) of the tumour. One of the mechanisms of tumoural
      progression consists in the protein inactivation resulting from the NO nitration
      of tyrosine from proteins coded for by tumour-suppressing genes, such as p53.
      Furthermore, in malignant astrocytes, nitrosoglutathione, a natural NO-donor, has
      been seen to play a role in the chemoresistance displayed against nitrosourea
      derivatives. The NO excreted by irradiated astrocytoma cells also appears to be
      involved in the resistance to the radiotherapy shown by non-irradiated cells.
      CONCLUSIONS: The molecular mechanisms behind the complex and paradoxical activity
      of NO in glioblastoma multiforme have still not been fully explained and its
      implications in vivo are even further from being completely understood.

PMID- 15849680
TI  - [Mercury and neurotoxicity].
AB  - INTRODUCTION AND AIMS: Mercury is a metal that is widely used in hundreds of
      applications nowadays. This metal has proved to be extremely toxic in humans,
      especially for the central nervous system, both in cases of exposure from
      everyday applications (e.g. dental fillings) and from environmental exposure.
      Unfortunately, most of the research carried out on this metal is relatively
      recent and many questions remain unanswered. The aim of this work is to review
      all the knowledge we have at the present time about the mechanisms of action of
      this metal. DEVELOPMENT: To do so, we discuss the latest scientific findings
      about the toxic processes that are activated, as well as its effects on the
      cellular cytoskeleton, its genotoxicity or the production of compounds that have
      been linked to neurodegeneration. CONCLUSIONS: Its prolonged period of latency,
      ambiguous symptoms and the activation of generalised toxic mechanisms call for
      urgent efforts to be made in basic research to help determine as clearly as
      possible the way this metal acts in the body. This knowledge will provide us not
      only with the way to obtain therapies but also with the hope of developing
      biomarkers that make it possible to carry out early and reliable diagnoses of the
      damage done and of individual susceptibility.

PMID- 15849681
TI  - [Cerebrovascular disease and temporal arteritis].

PMID- 15849682
TI  - What to do?

PMID- 15849684
TI  - Aprepitant for the control of chemotherapy induced nausea and vomiting in
      adolescents.
AB  - Nausea and vomiting are common side effects of chemotherapy in adult and
      pediatric patients. Even with standard antiemetic therapy, a significant number
      of patients continue to experience acute and delayed symptoms. When used in
      combination with standard antiemetic therapy, a new class of antiemetics, the
      neurokinin-1 (NK-1) receptor antagonists, have been shown to improve both acute
      and delayed nausea and vomiting in adults. In this report, we describe the NK-1
      receptor antagonist aprepitant in two adolescent patients receiving highly
      emetogenic chemotherapy who had experienced refractory nausea and vomiting with
      previous chemotherapy courses. The addition of aprepitant to the antiemetic
      regimen in the patients resulted in significant subjective improvement in nausea
      and vomiting as well as quality of life. These results in our adolescent patients
      are promising, but there is a need for well-designed studies to determine the
      efficacy, dosing, and safety of aprepitant in children of all ages.

PMID- 15849688
TI  - New developments in the asymmetric Stetter reaction.

PMID- 15849689
TI  - Branching out of single-molecule fluorescence spectroscopy: challenges for
      chemistry and influence on biology.
AB  - In the last decade emerging single-molecule fluorescence-spectroscopy tools have
      been developed and adapted to analyze individual molecules under various
      conditions. Single-molecule-sensitive optical techniques are now well established
      and help to increase our understanding of complex problems in different
      disciplines ranging from materials science to cell biology. Previous dreams, such
      as the monitoring of the motility and structural changes of single motor proteins
      in living cells or the detection of single-copy genes and the determination of
      their distance from polymerase molecules in transcription factories in the
      nucleus of a living cell, no longer constitute unsolvable problems. In this
      Review we demonstrate that single-molecule fluorescence spectroscopy has become
      an independent discipline capable of solving problems in molecular biology. We
      outline the challenges and future prospects for optical single-molecule
      techniques which can be used in combination with smart labeling strategies to
      yield quantitative three-dimensional information about the dynamic organization
      of living cells.

PMID- 15849690
TI  - Molecular recognition by glycoside pseudo base pairs and triples in an apramycin
      RNA complex.

PMID- 15849691
TI  - Preventing crystallization of phospholipids in monolayers: a new approach to lung
      surfactant therapy.

PMID- 15849693
TI  - Simultaneous COD, nitrogen, and phosphate removal by aerobic granular sludge.
AB  - Aerobic granular sludge technology offers a possibility to design compact
      wastewater treatment plants based on simultaneous chemical oxygen demand (COD),
      nitrogen and phosphate removal in one sequencing batch reactor. In earlier
      studies, it was shown that aerobic granules, cultivated with an aerobic pulse
      feeding pattern, were not stable at low dissolved oxygen concentrations.
      Selection for slow-growing organisms such as phosphate-accumulating organisms
      (PAO) was shown to be a measure for improved granule stability, particularly at
      low oxygen concentrations. Moreover, this allows long feeding periods needed for
      economically feasible full-scale applications. Simultaneous nutrient removal was
      possible, because of heterotrophic growth inside the granules (denitrifying PAO).
      At low oxygen saturation (20%) high removal efficiencies were obtained; 100% COD
      removal, 94% phosphate (P-) removal and 94% total nitrogen (N-) removal (with
      100% ammonium removal). Experimental results strongly suggest that P-removal
      occurs partly by (biologically induced) precipitation. Monitoring the laboratory
      scale reactors for a long period showed that N-removal efficiency highly depends
      on the diameter of the granules.

PMID- 15849694
TI  - Stabilization of glucose oxidase in alginate microspheres with photoreactive
      diazoresin nanofilm coatings.
AB  - The nanoassembly and photo-crosslinking of diazo-resin (DAR) coatings on small
      alginate microspheres for stable enzyme entrapment is described. Multilayer
      nanofilms of DAR with poly(styrene sulfonate) (PSS) were used in an effort to
      stabilize the encapsulation of glucose oxidase enzyme for biosensor applications.
      The activity and physical encapsulation of the trapped enzyme were measured over
      24 weeks to compare the effectiveness of nanofilm coatings and crosslinking for
      stabilization. Uncoated spheres exhibited rapid loss of activity, retaining only
      20% of initial activity after one week, and a dramatic reduction in effective
      activity over 24 weeks, whereas the uncrosslinked and crosslinked {DAR/PSS}
      coated spheres retained more than 50% of their initial activity after 4 weeks,
      which remained stable even after 24 weeks for the two and three bilayer films.
      Nanofilms comprising more polyelectrolyte layers maintained higher overall
      activity compared to films of the same composition but fewer layers, and
      crosslinking the films increased retention of activity over uncrosslinked films
      after 24 weeks. These findings demonstrate that enzyme immobilization and
      stabilization can be achieved by using simple modifications to the layer-by-layer
      self-assembly technique.

PMID- 15849695
TI  - Improved yield of recombinant merozoite Surface protein 3 (MSP3) from Pichia
      pastoris using chemically defined media.
AB  - Plasmodium falciparum merozoite surface protein 3 (MSP3) is a leading blood-stage
      malaria vaccine candidate. Vaccination with Pichia pastoris derived recombinant
      MSP3 protected Aotus nacymai monkeys from the parasite's lethal challenge and the
      post-challenge antibody titer against MSP3 correlated with protection. In our
      preliminary attempts to produce this vaccine in fermentors, little or no
      expression of MSP3 was observed in chemically defined media, although the same P.
      pastoris strain produced MSP3 in complex media. Our goal is to develop a Phase
      I/II clinical manufacturing process in completely chemically defined media
      because of the concern of potential prion contamination in complex media
      containing animal derived products. Here, we report our investigations into
      various factors to improve the yield of MSP3 in defined media. We found that an
      induction pH (pH(i)) 6.8 yielded MSP3 at 434 mg/L whereas there was no product at
      pH(i)< or = 5, though cell growth was the same in all pH(i) levels examined. High
      levels of NH(4) (+) consumed at pH(i) 6.8 were directly correlated to the
      enhanced MSP3 production. Furthermore, an additional 3.5-fold increase in the
      yield of MSP3 was obtained by addition of casamino acids at pH(i) 6.8. No direct
      correlation was observed between protease activity in the culture supernatants
      and lack of MSP3 expression. Neither high P. pastoris biomass generated at a high
      specific growth rate (0.04/h) nor low induction temperatures during induction
      improved yield. Nitrogen source was the most important factor affecting
      expression of MSP3 in defined media.

PMID- 15849696
TI  - Validating signals of ovulation: do women who think they know, really know?
AB  - This study was carried out to test whether women who think they know when they
      ovulate, really know. Fifty-three women of age 18.7 to 46.1 (mean age 28.4 years)
      participated in initial interviews about ovulation. Criteria for recruitment
      included perceived ovulation, regular menstrual cycles, and not using hormonal
      contraception. Women collected and refrigerated urine samples from day 5 until
      they thought they ovulated. Samples collected within 48 h of the perceived signal
      were then tested for a pre-ovulatory LH surge. Of the 53 original participants,
      36 women provided urine samples for 1-6 cycles, so that 87 cycles were tested.
      Subjective signals of ovulation varied between women and between cycles but
      included abdominal pain and changes in cervical discharge, libido, and mood. Of
      the 87 cycles tested, during which women identified one or multiple signals of
      ovulation, 37 of the 87 urine specimens tested positive for an LH surge for a
      concordance rate of 42.5%. Using the first tested cycle from the 36 women who
      provided urine specimens, 13 of those specimens demonstrated an LH surge, for a
      concordance rate of 36.1%. That rate dropped to 28% (7/25) when women who used
      basal body temperature as an ovulatory signal were excluded. Finally, the mean
      level of accuracy among the 15 women who contributed 3-6 urine specimens for
      testing was 48.9%. The results of this study demonstrate a low degree of
      concordance between LH surge and perceived ovulation among women who think they
      know when they ovulate. The most motivated study participants were right about
      half of the time. Although there is variation among women in their ability to
      know when they ovulate, this study suggests that, for most women, ovulation is
      concealed.

PMID- 15849697
TI  - Folding of a misfolding-prone beta-galactosidase in absence of DnaK.
AB  - In absence of chaperone DnaK, bacterially produced misfolding-prone proteins
      aggregate into large inclusion bodies, but still a significant part of these
      polypeptides remains in the soluble cell fraction. The functional analysis of the
      model beta-galactosidase fusion protein VP1LAC produced in DnaK(-) cells has
      revealed that the soluble version exhibits important folding defects and that it
      is less stable and less active than when produced in wild-type DnaK(+) cells. In
      addition, we have observed that the induction of gene expression at the very late
      exponential phase enhances twofold the stability of VP1LAC, a fact that in DnaK(
      ) background results in a dramatic increase of its specific activity up to
      phenotypically detectable levels. These results indicate that the chaperone DnaK
      is critical for the folding of misfolding-prone proteins and also that the
      soluble form reached in its absence by a fraction of polypeptides is not
      necessarily supportive of biological activity. In the case of E. coli beta
      galactosidase, the catalytic activity requires assembling into tetramers and the
      fine organization of the activating interfaces holding the active sites, what
      might not be properly reached in absence of DnaK.

PMID- 15849698
TI  - Body mass index and old-age survival: a comparative study between the Union Army
      Records and the NHANES-I Epidemiological Follow-Up Sample.
AB  - On the basis of a historical review of the BMI trend among white male Americans
      since the late 19th century, this paper investigates the association between BMI
      measured at age 50-59 years and survival in the subsequent 18 years of follow-up
      through a comparative study between the Union Army Records (n = 1,238) and the
      1971-1975 National Health and Nutritional Examination Survey Epidemiological
      Follow-up Sample (n = 861). A descriptive analysis of the trend in BMI suggests
      that the age-adjusted average BMI among adult white males has increased from 22.8
      in the late 19th century to 28.0 in the year of 2000. The corresponding increase
      in the age-adjusted percentage of obesity is from 2.5% to 28.2%. Given the
      significant increase in BMI, it becomes important to evaluate how the BMI
      mortality association has changed since the 19th century, and what implications
      these changes might have to mortality in the future. The results from the Cox
      proportional hazard analysis indicate that as the average BMI at population level
      increases, the optimal BMI in terms of survival increases, rather than stable.
      With the whole American population moving into a higher BMI regime, the optimal
      BMI in terms of old-age survival for white male Americans has experienced a
      substantial upward shift, from 20.6-23.6 in the late 19th century to 22.7-27.3 in
      the early 1970s. Mortality differentials across BMI quintiles have become more
      salient since the late 19th century. There is still good potential for old-age
      mortality to further decline. However, to what extent this potential can be
      developed will partially depend on the future trend in the prevalence of obesity.

PMID- 15849699
TI  - Gender and nutritional status at the household level among Gwembe Valley Tonga
      children, 0-10 years.
AB  - Gender bias usually favors males, yet among the matrilineal Gwembe Tonga of
      Zambia, females appear to receive preferential treatment. It is hypothesized that
      children in polygynous households will have increased levels of malnutrition due
      to the dilution of resources. Further, if gender bias is observed, it will favor
      females. The presence of preferential treatment during preadolescence is assessed
      by measuring physical status in the household. Monogamous or polygynous status of
      households is considered in this analysis of 188 children of age 0-10 years. The
      sample, 63 households from two rural villages, includes 47 females and 49 males
      in monogamous households and 52 females and 40 males in polygynous households.
      Comparisons of nutritional status are made with < or =-2.0 SD as indicative of
      stunting (height-for-age), wasting (weight-for-height), and chronic underweight
      (weight-for-age). Boys have better nutrition in monogamous households-40.8%
      stunted and 24.5% underweight compared to 62.5% stunted (P = 0.021), 42.5%
      underweight (P = 0.036) in polygynous households. Female stunting does not differ
      significantly by household type (40.4% monogamous, 42.3% polygynous). Low levels
      of wasting in either sex regardless of household type were observed. Girls have
      better physical status than boys in polygynous households, thereby supporting our
      combined hypotheses and demonstrating gender bias in pre-adolescents.

PMID- 15849700
TI  - The use of the terms bipolar and tetrapolar.

PMID- 15849701
TI  - Modeling the effects of health status and the educational infrastructure on the
      cognitive development of Tanzanian schoolchildren.
AB  - This paper models the proximate determinants of school attendance and scores on
      cognitive and educational achievement tests and on school examinations of over
      600 schoolchildren from the Control group of a randomized trial in Tanzania,
      where children in the Intervention group heavily infected with hookworm and
      schistosomiasis received treatment. The modeling approach used a random effects
      framework and incorporated the inter-relationships between school attendance and
      performance on various tests, controlling for children's health status,
      socioeconomic variables, grade level, and the educational infrastructure. The
      empirical results showed the importance of variables such as children's height
      and hemoglobin concentration for the scores, especially on educational
      achievement tests that are easy to implement in developing countries. Also,
      teacher experience and work assignments were significant predictors of the scores
      on educational achievement tests, and there was some evidence of multiplicative
      effects of children's heights and work assignments on the test scores. Lastly,
      some comparisons were made for changes in test scores of treated children in the
      Intervention group with the untreated children in the Control group.

PMID- 15849702
TI  - Intraobserver error associated with measurements of the hand.
AB  - Measurements of the hand are common in studies that use anthropometric data.
      However, despite widespread usage, relatively few studies have formally assessed
      the degree of measurement error associated with standard measurements of the
      hand. This is significant because high amounts of measurement error can
      invalidate statistical results. In this paper, intraobserver precision estimates
      for measures of total hand length and total 3rd-digit length were evaluated from
      repeated measures on 90 subjects (180 separate hands and fingers). From this
      replicate data, three precision estimates were calculated: the technical error of
      measurement (TEM), the relative technical error of measurement (rTEM), and the
      coefficient of reliability (R). For both measurements, all three estimates
      yielded a very high degree of precision (TEM < 2 mm, rTEM < 1%, and R > or =
      0.95). These results suggest that both total hand length and 3rd-digit length are
      sufficiently precise for anthropometric research applications.

PMID- 15849703
TI  - Postnatal salivary cortisol and sense of coherence (SOC) in Eritrean mothers.
AB  - This pilot study explores possible physiological correlates of maternal sense of
      coherence (SOC) by looking at salivary cortisol levels in Eritrean mothers during
      the immediate pre- and postnatal period. Samples of pre- and postnatal resting
      whole saliva were obtained from 19 mothers and from 31 controls in Ghinda.
      Radioimmunoassay results revealed no differences between prenatal and control
      concentrations of salivary cortisol, but postnatal levels were significantly
      lower (P < 0.014). Mothers who delivered in hospital had significantly higher SOC
      scores compared to those who opted for home birth (P < 0.045). This difference
      was particularly pronounced in the comprehensibility subscale of the SOC scores
      (P < 0.037). Moreover, mothers with higher comprehensibility scores showed
      significantly lower postnatal cortisol levels (P < 0.017). No associations were
      found between cortisol and age or parity. The implications of these findings for
      maternity health service policy and practice in Eritrea are considered.

PMID- 15849704
TI  - Age at natural menopause in Spain and the United States: results from the DAMES
      project.
AB  - Our research was undertaken to determine the median age of natural menopause and
      correlates of the timing of menopause in Spain and the United States (U.S.). A
      population-based sample of 300 women from Madrid, Spain and a random sample of
      293 women from Fallon Community Health plan (FCHP), a health maintenance
      organization (HMO) in central Massachusetts, were interviewed using a semi
      structured questionnaire. Logit analysis and logistic regression were used to
      estimate the median age at menopause and identify factors associated with it. The
      median age of natural menopause in Spain is estimated at 51.7 years, and in the
      U.S., it is 52.6 years. In Spain, women with any children (OR = 0.58, 95% CI:
      0.25, 1.36) and a lower body mass index (BMI) (OR = 0.45, 95% CI: 0.27, 0.78) had
      later ages at menopause while current smokers (OR = 5.51, 95% CI: 1.82, 16.7) had
      earlier ages of menopause in a multivariate model. A multiplicative interaction
      between smoking status and parity was identified, and an interaction term
      included in the multivariate model (OR = 0.58, 95% CI: 0.35, 0.94). In the U.S.,
      household income, marital status, and education level were statistically
      associated with age at natural menopause in bivariate models. These factors were
      no longer statistically significant after adjustments in a multivariate model.
      Oral contraceptive use, cycle length, and cycle regularity were not statistically
      associated with the age of menopause in either country. The ages of natural
      menopause in Spain and the U.S. are comparable to other industrialized nations.
      The factors associated with the timing of natural menopause, in particular
      smoking and BMI, are consistent with those identified in previous studies.

PMID- 15849705
TI  - Stature and adiposity among children in contrasting neighborhoods in the city of
      Hamilton, Ontario, Canada.
AB  - It is hypothesized in this study that body size and shape vary by local area
      within the North American urban environment. This study tests that hypothesis by
      comparing stature and adiposity among children (of age 6-10 years) attending
      elementary schools in three neighborhoods that contrast by socioeconomic status
      and recent immigrant status. While the whole sample of children (n = 266) has
      27.4% of children that can be classified as overweight/obese (> or =85th
      percentile for body mass index), analysis by socioeconomic status (SES) reveals
      that there are approximately twice as many children in the overweight/obese
      category in the two low-SES schools compared to the high-SES school. Further
      analysis by individual school indicates that the school in the poorest
      neighborhood has a statistically significantly lower mean height-for-age Z score
      relative to the most affluent school. It is concluded that the influence of
      socioeconomic, demographic, and environmental factors on stature and adiposity
      can be investigated through studies such as this one that consider local area
      variation.

PMID- 15849706
TI  - Height, weight, and body mass index among Akwesasne Mohawk youth.
AB  - Information on the growth of contemporary Native American adolescents is limited.
      A few studies have shown that Native Americans have growth patterns that may
      differ from U.S. reference values. We describe basic anthropometric
      characteristics (height and weight) of Mohawk youth between the ages of 10.0 and
      16.99 years from the Akwesasne Mohawk Nation. Body mass index (BMI) was
      calculated. Mean height of Akwesasne Mohawk youth approximates the 50th
      percentile of reference values as determined by the 2000 Center for Disease
      Control and Prevention (CDC) growth charts. At every age, weight means of males
      approximate or exceed the 90th percentile and all mean weights of females
      approximate the 85th percentile. Akwesasne males are significantly taller than
      females from age 14 on and significantly heavier at ages 14 and 16. All age
      specific BMI means for males are at or above the 90th percentile and females'
      means are at or above the 85th. The potential for long-term health effects
      associated with being overweight has implications for the future health of young
      Native Americans.

PMID- 15849707
TI  - Implication of Ariaal sexual mixing on gonorrhea.
AB  - Recent research on sexual mixing in populations of sub-Saharan Africa raises the
      question as to whether STDs can persist in these populations without the presence
      of a core group. A mathematical model is constructed for the spread of gonorrhea
      among the Ariaal population of Northern Kenya. A formula for the basic
      reproduction number R(0) (the expected number of secondary infections caused by a
      single new infective introduced into a susceptible population) is determined for
      this population in the absence of a core group. Survey data taken in 2003 on
      sexual behavior from the Ariaal population are used in the model which is
      formulated for their age-set system including four subpopulations: single and
      married, female and male. Parameters derived from the data, and other information
      from sub-Saharan Africa are used to estimate R(0). Results indicate that, even
      with the elevating effect of the age-set system, the disease should die out since
      R(0) < 1. Thus, the persistence of gonorrhea in the population must be due to
      factors not included in the model, for example, a core group of commercial sex
      workers or concurrent partnerships.

PMID- 15849708
TI  - Developmental origins of adult disease: Barker's or Dorner's hypothesis?

PMID- 15849709
TI  - Enhanced collection of fingerprints and ridge counting.

PMID- 15849710
TI  - Growth velocity standards from longitudinally measured infants of age 0-2 years
      born in Shiraz, southern Iran.
AB  - This paper presents growth velocity data for a cohort of 317 infants (164 girls
      and 153 boys) born in Shiraz, southern Iran, in 1996 and followed longitudinally
      for 2 years. The growth velocity of five anthropometric measurements (height,
      weight, arm, head, and chest circumferences) declined rapidly from 2 weeks to 7
      months of age and less steeply thereafter for both sexes. Growth velocities for
      boys were higher than girls in the first months but did not differ significantly
      later on. However, growth velocity centiles for girls lie below those for boys
      throughout the age range studied. Weight velocities in the Iranian infants were
      significantly lower than for corresponding infants in the U.K., the Middle East,
      and Africa, but height velocities were generally higher.

PMID- 15849711
TI  - Energetics of nose and mouth breathing, body size, body composition, and nose
      volume in young adult males and females.
AB  - This research tests the relative ability of body size factors and sex to explain
      variation in nose volume and to explain metabolic measures during rest and
      moderate exercise in 50 young adults. It uses standard anthropometric measures
      plus two new measures of nose morphology (nose/face angle and nose volume) and
      evaluates body composition with a device for air displacement plethysmography.
      Standard physiological measures were obtained in nose-only and mouth-only
      breathing conditions with subjects at rest and using moderate exercise. A factor
      representing linear and bulk measures of body size and a factor representing lean
      body mass explain subjects' variation in nose volume, resting volume of oxygen
      consumed (VO2), and resting ventilation volume (VV) better than subject's sex
      does. By contrast, during exercise, sex explains VO2 and VV better than do body
      size factors, probably because hormone-mediated muscularity in males produced
      greater work output. Nose breathing was found to be more energetically efficient
      in most but not all subjects, but additional research is needed to explore this
      finding further. Qualitative comparisons between modes of breathing and the
      application of this research protocol to studies of climate-related patterns of
      nasal variation are discussed.

PMID- 15849712
TI  - "Central command" and insular activation during attempted foot lifting in
      paraplegic humans.
AB  - The relationship between cardiovascular regulation and brain activation was
      investigated during attempted foot lifting in paraplegic subjects and during
      rhythmic handgrip exercise at one-third of maximum voluntary contraction force.
      Brain areas of interest were the primary sensory-motor area and the insula, a
      hypothesized center for a central nervous feed-forward mechanism involved in
      cardiovascular control ("central command"). This mechanism is complementary to
      the usual known feedback pathways such as skeletal muscle afferent signals.
      Regional cerebral blood flow (rCBF) was measured in eight normal and three
      paraplegic subjects using positron emission tomography (PET) and oxygen-15
      labeled water. Statistical parametric maps were calculated from the images
      comparing rest and handgrip. Paraplegics were also scanned during attempted foot
      lifting, a condition without sensory feedback. During activation tasks, heart
      rate and mean arterial pressure increased. PET activation responses (P < 0.05,
      corrected for multiple comparisons) were found in the contralateral primary
      sensory-motor area, the supplementary motor area, ipsilateral cerebellum, and
      bilaterally in the insula. A conjunction analysis showing responses common to
      handgrip and attempted foot lifting revealed activation in the right central
      insula (P < 0.05, corrected) in concordance with the concept of a central command
      feed-forward hypothesis.

PMID- 15849713
TI  - Processing lexical semantic and syntactic information in first and second
      language: fMRI evidence from German and Russian.
AB  - We introduce two experiments that explored syntactic and semantic processing of
      spoken sentences by native and non-native speakers. In the first experiment, the
      neural substrates corresponding to detection of syntactic and semantic violations
      were determined in native speakers of two typologically different languages using
      functional magnetic resonance imaging (fMRI). The results show that the
      underlying neural response of participants to stimuli across different native
      languages is quite similar. In the second experiment, we investigated how non
      native speakers of a language process the same stimuli presented in the first
      experiment. First, the results show a more similar pattern of increased
      activation between native and non-native speakers in response to semantic
      violations than to syntactic violations. Second, the non-native speakers were
      observed to employ specific portions of the frontotemporal language network
      differently from those employed by native speakers. These regions included the
      inferior frontal gyrus (IFG), superior temporal gyrus (STG), and subcortical
      structures of the basal ganglia.

PMID- 15849714
TI  - Ciliary behavior of a negatively phototactic Chlamydomonas reinhardtii.
AB  - With an instrument that can record the motion of both cilia of the unicellular
      alga Chlamydomonas reinhardtii for many hours, the behavioral differences of its
      two cilia have been studied to determine their specific role in phototaxis. The
      organism was held on a fixed micropipette with the plane of ciliary beating
      rotated into the imaging plane of a quadrant photodetector. The responses to
      square-wave light patterns of a wide range of temporal frequencies were used to
      characterize the responses of each cilium. Eighty-one cells were examined showing
      an unexpectedly diverse range of responses. Plausible common signals for the
      linear and nonlinear signals from the cell body are suggested. Three independent
      ciliary measures--the beat frequency, stroke velocity, and phasing of the two
      cilia--have been identified. The cell body communicates to the cilia the
      direction of phototaxis the cell desires to go, the absolute light intensity, and
      the appropriate graded transient response for tracking the light source. The
      complexity revealed by each measure of the ciliary response indicates many
      independent variables are involved in the net phototactic response. In spite of
      their morphological similarity, the two cilia of Chlamydomonas respond uniquely.
      Probably the signals from the cell body fan out to independent pathways in the
      cilia. Each cilium modifies the input in its own way. The change in the pattern
      of the effective and recovery strokes of each cilium associated with negative
      phototaxis has been demonstrated and its involvement in phototactic turning is
      described.

PMID- 15849715
TI  - Temporal resolving power of spin echo and gradient echo fMRI at 3T with apparent
      diffusion coefficient compartmentalization.
AB  - The temporal resolving power of blood oxygenation level-dependent (BOLD)
      functional magnetic resonance imaging (fMRI) at 3T was investigated in the visual
      and auditory cortices of the human brain. By using controlled temporal delays and
      selective visual hemifield stimulation, regions with similar (left vs. right
      occipital cortex) and different (occipital cortex vs. auditory cortex) vascular
      architectures were compared. Estimates of the time-to-peak (TTP) of the BOLD
      hemodynamic response function (hrf) were obtained using a spin echo (SE) sequence
      and compared to those acquired using a traditional gradient echo (GE) sequence.
      The hrf TTP in the visual cortex was found to be 4.73 s and 4.21 s for GE and SE,
      respectively. The auditory cortex response was significantly delayed, with TTPs
      of 4.95 s and 4.51 s for GE and SE, respectively. The GE response was able to
      resolve visual stimuli separated by 250 ms, whereas SE could resolve stimuli 500
      ms apart. Apparent-diffusion-coefficient (ADC) compartmentalization of the BOLD
      signal was applied to restrict the vascular sensitivity of the SE and GE
      sequences. Limiting the response to voxels with ADCs < 0.8 x 10(-3) mm(2)/s
      improved the temporal resolving power of GE and SE BOLD to 125 ms and 250 ms,
      respectively.

PMID- 15849716
TI  - Modulation of UDP-glucuronosyltransferase 1A1 in primary human hepatocytes by
      prototypical inducers.
AB  - The primary objective of this study was to evaluate the modulation of UGT1A1
      expression in human hepatocytes using prototypical CYP450 inducers. A bank of 16
      human livers was utilized to obtain an estimate of the range of UGT1A1 protein
      expression and catalytic activity. Concentration-dependent changes in UGT1A1
      response were evaluated in hepatocyte cultures after treatment with 3
      methylchloranthrene, beta-napthoflavone, rifampicin, or phenobarbital.
      Pharmacodynamic analyses of UGT1A1 expression were conducted and compared to
      those of CYP450 after treatment with inducers in 2-3 different hepatocyte
      preparations. Additionally, expression of UGT1A1 mRNA and protein was evaluated
      in human hepatocytes treated with 14 different compounds known to activate
      differentially the human pregnane-X-receptor or constitutive androstane receptor.
      Pharmacodynamic modeling revealed EC50 values statistically significant between
      UGT1A1 and CYP2B6 after treatment with PB, but not statistically distinguishable
      between UGT1A1 and CYP's 1A2 or 3A4 after treatment with 3-methylchloranthrene or
      rifampicin, respectively. UGT1A1 was most responsive to the pregnane-X-receptor
      agonists rifampicin, ritonavir, and clotrimazole at the mRNA level and, to a
      lesser extent, the constitutive androstane receptor-activators, phenobarbital and
      phenytoin. Pharmacodynamic analyses support a mechanism of coordinate regulation
      between UGT1A1 and a number of CYP450 enzymes by multiple nuclear receptors.

PMID- 15849717
TI  - Response of the antioxidant defense system to tert-butyl hydroperoxide and
      hydrogen peroxide in a human hepatoma cell line (HepG2).
AB  - The aim of this work was to investigate the response of the antioxidant defense
      system to two oxidative stressors, hydrogen peroxide and tert-butyl
      hydroperoxide, in HepG2 cells in culture. The parameters evaluated included
      enzyme activity and gene expression of superoxide dismutase, catalase,
      glutathione peroxidase, and activity of glutathione reductase. Besides, markers
      of the cell damage and oxidative stress evoked by the stressors such as cell
      viability, intracellular reactive oxygen species generation, malondialdehyde
      levels, and reduced glutathione concentration were evaluated. Both stressors,
      hydrogen peroxide and tert-butyl hydroperoxide, enhanced cell damage and reactive
      oxygen species generation at doses above 50 microM. The concentration of reduced
      glutathione decreased, and levels of malondialdehyde and activity of the
      antioxidant enzymes consistently increased only when HepG2 cells were treated
      with tert-butyl hydroperoxide but not when hydrogen peroxide was used. A slight
      increase in the gene expression of Cu/Zn superoxide dismutase and catalase with
      500 microM tert-butyl hydroperoxide and of catalase with 200 microM hydrogen
      peroxide was observed. The response of the components of the antioxidant defense
      system evaluated in this study indicates that tert-butyl hydroperoxide evokes a
      consistent cellular stress in HepG2.

PMID- 15849718
TI  - Effects of age and pregnancy on cytochrome P450 induction by
      octamethyltetracyclosiloxane in female Sprague-Dawley rats.
AB  - Dimethylcyclosiloxanes (DMCS) are components of silicone gel containing implants
      and are known inducers of human drug metabolizing enzymes. The effects of the
      major DMCS, octamethyltetracyclosiloxane (D4) on cytochrome P450 (CYP) induction
      were examined in young adult, mature, and pregnant female Sprague-Dawley rats.
      Also, the ability of D4 administered to pregnant dams to affect CYP expression in
      fetal liver was examined. Female young, mature, and pregnant Sprague-Dawley rats
      were administered 0, 5, 20, and 100 mg/kg D4 daily by gavage for 8 days. Liver
      microsomal CYP (CYP2B, CYP3A, CYP1A) concentrations were evaluated by Western
      blots using specific antisera, and CYP activities were assayed using CYP
      selective assays. D4 treatment resulted in a significant induction of CYP2B and
      CYP3A isoforms. CYP induction was dose and age dependent. A comparison of the
      inducibility of CYP3A protein by D4 in rats from different age groups showed that
      the degree of increase was the highest in the pregnant rats at doses of 20 mg/kg
      D4 or higher. The mature rats had a lesser degree of responsiveness than did the
      young rats at the dose of 100 mg/ kg D4. Significant increases in CYP2B
      immunoreactive protein concentrations were observed in young and mature rats
      given D4 at doses >5 mg/kg and in pregnant rats at doses >20 mg/kg. Maximal CYP2B
      induction detected with blotting was more than 90-fold in mature rats; however,
      no significant changes were detected in CYP1A expression. There was a 20%
      increase of liver to body weight ratio in the mature rats treated with 100 mg/kg
      D4. D4 has different inductive properties in female rats of different ages and
      reproductive status. Also, D4 administered to the pregnant dam is capable of
      inducing CYP expression in fetal liver as well as decreasing fetal body weight.

PMID- 15849719
TI  - Characterization of adjacent E-box and nuclear factor 1-like DNA binding sequence
      in the human CYP1A2 promoter.
AB  - To better understand the molecular mechanisms of cytochrome P450 1A2 (CYP1A2)
      regulation, we have characterized a region of the promoter (+3 to -176) that
      contains a single E-box and an adjacent nuclear factor 1 (NF1)-like DNA binding
      site. The E-box was shown to specifically bind nuclear proteins that were
      recognized by antibodies against upstream stimulatory factor (USF) 1 and 2.
      Comparison of NF1 binding proteins in HepG2 cells and primary cultures of rat
      hepatocytes revealed different patterns of DNA-protein complexes, all of which
      were recognized by a general NF1 antibody. Mutations of the E-box resulted in
      substantial reduction of promoter activity in either primary hepatocytes or HepG2
      cells regardless of the presence in the reporter constructs of other CYP1A2
      regulatory elements, such as the hepatic nuclear factor 1 (HNF-1) binding site.
      In contrast, reporter gene activity of the promoter construct harboring the
      mutated NF1-like binding site was affected by upstream sequences when transfected
      into HepG2 cells, but not in primary hepatocytes. We conclude that both USF
      proteins and different isoforms of NF1 contribute to the constitutive expression
      of CYP1A2.

PMID- 15849720
TI  - Toxicity of short-chain alcohols to the nematode Caenorhabditis elegans: a
      comparison of endpoints.
AB  - The toxicities of 4 short-chain alcohols--namely methanol, ethanol, iso-propanol
      and iso-butanol--were compared in the nematode Caenorhabditis elegans using
      several different ecotoxicological endpoints. Range-finding tests were conducted
      using transgenic PC161 worms carrying a double reporter construct (GFP plus lacZ)
      linked to the stress-inducible hsp16-1 promoter. These tests showed little
      response from the GFP reporter, but gave good dose-response curves for the lacZ
      reporter--showing clear induction at 0.5% v/v ethanol in an overnight assay, but
      only at 4% in a shorter 6-h assay. Comparison of the short-term dose-response
      curves shows a confusing pattern of differences between the four alcohols tested,
      although dose-dependence is evident across at least part of the concentration
      range. Feeding inhibition assays are somewhat inconclusive with regard to alcohol
      type, although iso-butanol and iso-propanol appear more toxic than ethanol, while
      methanol is least toxic. To resolve some of the remaining ambiguities, we also
      used a fecundity assay to show that iso-propanol is more toxic than ethanol, and
      a lethality assay to show that iso-butanol is more toxic than iso-propanol. Most
      of the endpoints studied are consistent with the following order of toxicity: iso
      butanol > iso-propanol > ethanol > or = methanol.

PMID- 15849721
TI  - In vivo and in vitro oxidative regulation of rat aryl sulfotransferase IV (AST
      IV).
AB  - Sulfotransferase catalyzed sulfation is important in the regulation of different
      hormones and the metabolism of hydroxyl containing xenobiotics. In the present
      investigation, we examined the effects of hyperoxia on aryl sulfotransferase IV
      in rat lungs in vivo. The enzyme activity of aryl sulfotransferase IV increased 3
      to 8-fold in >95% O2 treated rat lungs. However, hyperoxic exposure did not
      change the mRNA and protein levels of aryl sulfotransferase IV in lungs as
      revealed by Western blot and RT-PCR. This suggests that oxidative regulation
      occurs at the level of protein modification. The increase of nonprotein soluble
      thiol and reduced glutathione (GSH)/oxidized glutathione (GSSG) ratios in treated
      lung cytosols correlated well with the aryl sulfotransferase IV activity
      increase. In vitro, rat liver cytosol 2-naphthol sulfation activity was activated
      by GSH and inactivated by GSSG. Our results suggest that Cys residue chemical
      modification is responsible for the in vivo and in vitro oxidative regulation.
      The molecular modeling structure of aryl sulfotransferase IV supports this
      conclusion. Our gel filtration chromatography results demonstrated that neither
      GSH nor GSSG treatment changed the existing aryl sulfotransferase IV dimer status
      in cytosol, suggesting that oxidative regulation of aryl sulfotransferase IV is
      not caused by dimer-monomer status change.

PMID- 15849722
TI  - Actin polymerization promotes the reversal of streaming in the apex of pollen
      tubes.
AB  - Actin polymerization is important in the control of pollen tube growth. Thus,
      treatment of pollen tubes with low concentrations of latrunculin B (Lat-B), which
      inhibits actin polymerization, permits streaming but reversibly blocks
      oscillatory growth. In the current study, we employ Jasplakinolide (Jas), a
      sponge cyclodepsipeptide that stabilizes actin microfilaments and promotes
      polymerization. Uniquely, Jas (2 microM) blocks streaming in the shank of the
      tube, but induces the formation of a toroidal-shaped domain in the swollen apex,
      of which longitudinal optical sections exhibit circles of motion. The polarity of
      this rotary motion is identical to that of reverse fountain motility in control
      pollen tubes, with the forward direction occurring at the edge of the cell and
      the rearward direction in the cell interior. Support for the idea that actin
      polymerization in the apical domain contributes to the formation of this rotary
      motility activity derives from the appearance therein of aggregates and flared
      cables of F-actin, using immunofluorescence, and by the reduction in G-actin as
      indicated with fluorescent DNAse. In addition, Jas reduces the tip-focused Ca2+
      gradient. However, the alkaline band appears in the swollen apex and is spatially
      localized with the reverse fountain streaming activity. Taken together, our
      results support the idea that actin polymerization promotes reversal of streaming
      in the apex of the lily pollen tube.

PMID- 15849724
TI  - Risk factors for pancreatic cancer.
AB  - In the United States, the cumulative mortality or lifetime risk of dying from
      pancreatic cancer is about 1-2%, but although this form of cancer is rare, nearly
      all patients die from the disease within one to two years. Because of its
      lethality, pancreatic cancer now ranks fourth as a cause of death from cancer.
      There are country-specific differences in rates, perhaps explained by differences
      in life-style factors or diet. African-Americans in the USA have rates that are
      about 50% higher than Caucasians. Smoking is the major known risk factor for this
      cancer, explaining 20-30% of all cases. Another 5-10% of causes are caused by
      germline mutations, with mutations in BRCA2 being the most frequent. Two
      background diseases increase the risk of pancreatic cancer-pancreatitis, and
      diabetes. Major challenges presented by this cancer are: 1) determination of the
      molecular pathways that make this cancer so aggressive; 2) development of new
      modalities, perhaps based on proteomics, to enhance early detection.

PMID- 15849723
TI  - Low levels of arsenite activates nuclear factor-kappaB and activator protein-1 in
      immortalized mesencephalic cells.
AB  - Degeneration of dopaminergic neurons is one of the major features of Parkinson's
      disease. Many redox-active metals such as iron and manganese have been implicated
      in neuronal degeneration characterized by symptoms resembling Parkinson's
      disease. Even though, arsenic, which is another redox-active metal, has been
      shown to affect the central monoaminergic systems, but its potential in causing
      dopaminergic cell degeneration has not been fully known. Hence, the present study
      was designed to investigate arsenic signaling especially that is mediated by
      reactive oxygen species and its effect on early transcription factors in dopamine
      producing mesencephalic cell line 1RB3AN27. These mesencephalic cells were
      treated with low concentrations of sodium arsenite (0.1, 0.5, 1, 5, and 10
      microM) and incubated for different periods of time (0-4 h). Arsenite was
      cytotoxic at 5 and 10 microM concentrations only after 72-h incubation period.
      Arsenite, in a dose-dependent manner, induced generation of reactive oxygen
      species (ROS) and activation of early transcription factors such as nuclear
      factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) as shown by electro
      mobility shift assay. Incubation of antioxidants, either N-acetyl-L-cysteine (50
      microM) or alpha-tocopherol (50 microM) with 1 microM arsenite, suppressed ROS
      generation. Arsenite at 1 microM concentration was sufficient for maximal
      activation of NF-kappaB and AP-1 activation. Time kinetics studies showed maximal
      activation of NF-kappaB by 1 microM concentration of arsenite was seen at 120 min
      and correlated with complete degradation of Ikappa Balpha at 60 min. Similarly,
      maximal activation of AP-1 by 1 microM concentration of arsenite occurred at 120
      min. N-acetyl-L-cysteine at 50 microM concentration inhibited arsenite-induced NF
      kappa B and AP-1. In addition, arsenite was shown to induce phosphorylation of
      extracellular signal regulated kinase (ERK) 1/2 at concentrations of 1 microM and
      above. These results suggest that arsenite, at low and subcytoxic concentrations,
      appears to induce oxidative stress leading to activation of early transcription
      factors whereas addition of antioxidant inhibited the activation of these
      factors.

PMID- 15849725
TI  - Alkaline hemolysis fragility is dependent on cell shape: results from a
      morphology tracker.
AB  - BACKGROUND: The morphometric analysis of red blood cells (RBCs) is an important
      area of study and has been performed previously for fixed samples. We present a
      novel method for the analysis of morphologic changes of live erythrocytes as a
      function of time. We use this method to extract information on alkaline hemolysis
      fragility. Many other toxins lyse cells by membrane poration, which has been
      studied by averaging over cell populations. However, no quantitative data are
      available for changes in the morphology of individual cells during membrane
      poration-driven hemolysis or for the relation between cell shape and fragility.
      METHODS: Hydroxide, a porating agent, was generated in a microfluidic enclosure
      containing RBCs in suspension. Automatic cell recognition, tracking, and
      morphometric measurements were done by using a custom image analysis program.
      Cell area and circular shape factor (CSF) were measured over time for individual
      cells. Implementations were developed in MATLAB and on Kestrel, a parallel
      computer that affords higher speed that approaches real-time processing. RESULTS:
      The average CSF went through a first period of fast increase, corresponding to
      the conversion of discocytes to spherocytes under internal osmotic pressure,
      followed by another period of slow increase until the fast lysis event. For
      individual cells, the initial CSF was shown to be inversely correlated to cell
      lifetime (linear regression factor R=0.44), with discocytes surviving longer than
      spherocytes. The inflated cell surface area to volume ratio was also inversely
      correlated to lifetime (R=0.43) but not correlated to the CSF. Lifetime
      correlated best to the ratio of cell inflation volume (Vfinal-Vinitial) to
      surface area (R=0.65). CONCLUSIONS: RBCs inflate at a rate proportional to their
      surface area, in agreement with a constant flux model, and lyse after attaining a
      spherical morphology. Spherical RBCs display increased alkaline hemolysis
      fragility (shorter lifetimes), providing an explanation for the increased osmotic
      fragility of RBCs from patients who have spherocytosis.

PMID- 15849726
TI  - Antitumor effects of histone deacetylase inhibitor on Ewing's family tumors.
AB  - A chimeric protein, EWS-Fli1, identified in most Ewing's family tumors (EFTs) has
      been shown to be associated with the tumorigenicity of EFTs. We have previously
      reported that p21(Waf1/Cip1) expression was inhibited by EWS-Fli1 in EFTs.
      Histone deacetylase inhibitors (HDACIs) are known to up-regulate p21(Waf1/Cip1)
      expression in various cells and show promise as a cancer therapy. Here, we
      demonstrate the possible involvement of EWS-Fli1 in the activities of both
      histone acetylation and deacetylation, as well as the potential use of HDACIs as
      an antitumor agent for EFTs. A novel HDACI, FK228, strongly induced
      p21(Waf1/Cip1) expression, leading to the hypophosphorylation of retinoblastoma
      protein (Rb) in EFT cells. Results indicated that EWS-Fli1 deregulated histone
      acetylation through both the repression of histone acetyltransferase (HAT) and
      the enhancement of histone deacetylase (HDAC) activities in EFT cells. FK228
      treatment blocked both of the abnormal functions of EWS-Fli1. Expressions of EWS
      Fli1 protein and mRNA were also inhibited by HDACIs. We suggest that HDACIs might
      inhibit the expression of EWS-Fli1 via the suppression of the EWS promoter
      activity. FK228 demonstrated potent growth inhibitory effects on EFT cells at
      nanomolar concentrations, as well as an apparent distinction in the apoptotic
      effects between EFT and normal cells. Moreover, intraperitoneal administration of
      FK228 significantly inhibited tumor growth and induced apoptosis in EFTs in vivo.
      These results suggest that HDACI might be a promising reagent for use in
      molecular-based chemotherapy against EFTs.

PMID- 15849727
TI  - Overexpression of hypoxia-inducible factor HIF-1alpha predicts early relapse in
      breast cancer: retrospective study in a series of 745 patients.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that is
      involved in tumour growth and metastasis by regulating genes involved in response
      to hypoxia. HIF-1alpha protein overexpression has been shown in a variety of
      human cancers, but only 2 studies have documented the prognostic relevance of HIF
      1alpha expression in breast cancer. The aim of our study was to determine
      accurately the impact of HIF-1alpha expression on prognosis in a large series (n
      = 745) of unselected patients with invasive breast cancer in terms of overall
      survival, local recurrence and distant metastasis risk. HIF-1alpha expression was
      investigated using immunohistochemical assays on frozen sections, and correlated
      with patients' outcome (median follow-up = 13.5 years). Univariate (Kaplan-Meier)
      analysis showed that high levels of HIF-1alpha expression (cutoff = 10%)
      significantly correlated with poor overall survival (p = 0.019). HIF-1alpha
      expression correlated with high metastasis risk among the whole group of patients
      (p = 0.008). Multivariate analysis (Cox model) showed that the HIF-1alpha
      predictive value was independent of other current prognostic indicators. Moreover
      among node negative ones, HIF-1alpha expression was also significantly predictive
      of metastasis risk (p = 0.03) and of relapse (p = 0.035). All the data suggest
      that HIF-1alpha is associated with a worse prognosis in patients with invasive
      breast carcinoma. Furthermore HIF-1alpha immunodetection may be considered as a
      potential indicator for selecting patients who could benefit from specific
      therapies interfering with HIF-1alpha pathway.

PMID- 15849728
TI  - Diet and cancer: current knowledge, methodologic pitfalls and future directions.

PMID- 15849729
TI  - Polymorphisms in the DNA nucleotide excision repair genes and lung cancer risk in
      Xuan Wei, China.
AB  - The lung cancer mortality rate in Xuan Wei County is among the highest in China
      and has been attributed to exposure to indoor smoky coal emissions that contain
      very high levels of polycyclic aromatic hydrocarbons (PAHs). Nucleotide excision
      repair (NER) plays a key role in reversing DNA damage from exposure to
      environmental carcinogens, such as PAHs, that form bulky DNA adducts. We studied
      single nucleotide polymorphisms (SNPs) and their corresponding haplotypes in 6
      genes (ERCC1, ERCC2/XPD, ERCC4/XPF, ERCC5/XPG, RAD23B and XPC) involved in NER in
      a population-based case-control study of lung cancer in Xuan Wei. A total of 122
      incident primary lung cancer cases and 122 individually matched controls were
      enrolled. Three linked SNPs in ERCC2 were associated with lung cancer with
      similar ORs; e.g., persons with the Gln allele at codon 751 had a 60% reduction
      of lung cancer (OR = 0.40, 95% CI 0.18-0.89). Moreover, one haplotype in ERCC2
      was associated with a decreased risk of lung cancer (OR = 0.40, 95% CI 0.19-0.85)
      compared to the most common haplotype. In addition, subjects with one or 2 copies
      of the Val allele at codon 249 of RAD23B had a 2-fold increased risk of lung
      cancer (OR = 1.91, 95% CI 1.12-3.24). In summary, our results suggest that
      genetic variants in genes involved in the NER pathway may play a role in lung
      cancer susceptibility in Xuan Wei. However, due to the small sample size,
      additional studies are needed to evaluate these associations within Xuan Wei and
      in other populations with substantial environmental exposure to PAHs.

PMID- 15849730
TI  - Editors' comments, "Epidemiologic studies of nutrition and cancer".

PMID- 15849731
TI  - Epidemiologic studies of nutrition and cancer: let us not throw out the baby with
      the bath water.

PMID- 15849732
TI  - Potential anticancer activity of tanshinone IIA against human breast cancer.
AB  - Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a
      widely used Chinese herbal medicine. It has antioxidant properties and cytotoxic
      activity against multiple human cancer cell lines, inducing apoptosis and
      differentiation of some human cancer cell lines. Our purpose was to confirm its
      anticancer activity on human breast cancer in vitro and in vivo and to elucidate
      the mechanism of its activity. Human breast cancer cells were tested in vitro for
      cytotoxicity, colony formation inhibition, BrdU incorporation and gene expression
      profiling after treatment with tanshinone IIA. Seven nude mice bearing human
      breast infiltrating duct carcinoma orthotopically were tested for anticancer
      activity and expression of caspase-3 in vivo by s.c. injection of tanshinone IIA
      at a dose of 30 mg/kg 3 times/week for 10 weeks. Tanshinone IIA demonstrated a
      dose- and time-dependent inhibitory effect on cell growth (IC50 = 0.25
      microg/ml), and it significantly inhibited colony formation and BrdU
      incorporation of human breast cancer cells. Oligonucleotide microarray analysis
      identified 41 upregulated (1.22%) and 24 downregulated (0.71%) genes after
      tanshinone IIA treatment. Upregulated genes were involved predominantly in cycle
      regulation, cell proliferation, apoptosis, signal transduction and
      transcriptional regulation; and downregulated genes were associated mainly with
      apoptosis and extracellular matrix/adhesion molecules. A 44.91% tumor mass volume
      reduction and significant increase of casepase-3 protein expression were observed
      in vivo. Our findings suggest that tanshinone IIA might have potential anticancer
      activity on both ER-positive and -negative breast cancers, which could be
      attributed in part to its inhibition of proliferation and apoptosis induction of
      cancer cells through upregulation and downregulation of multiple genes involved
      in cell cycle regulation, cell proliferation, apoptosis, signal transduction,
      transcriptional regulation, angiogenesis, invasive potential and metastatic
      potential of cancer cells. ADPRTL1 might be the main target at which tanshinone
      IIA acted.

PMID- 15849733
TI  - Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German
      families suspected of hereditary nonpolyposis colorectal cancer.
AB  - Mutations in DNA MMR genes, mainly MSH2 and MLH1, account for the majority of
      HNPCC, an autosomal dominant predisposition to colorectal cancer and other
      malignancies. The evaluation of many questions regarding HNPCC requires
      clinically and genetically well-characterized HNPCC patient cohorts of reasonable
      size. One main focus of this multicenter study is the evaluation of the mutation
      spectrum and mutation frequencies in a large HNPCC cohort in Germany; 1,721
      unrelated patients, mainly of German descent, who met the Bethesda criteria were
      included in the study. In tumor samples of 1,377 patients, microsatellite
      analysis was successfully performed and the results were applied to select
      patients eligible for mutation analysis. In the patients meeting the strict
      Amsterdam criteria (AC) for HNPCC, 72% of the tumors exhibited high
      microsatellite instability (MSI-H) while only 37% of the tumors from patients
      fulfilling the less stringent criteria showed MSI-H; 454 index patients (406 MSI
      H and 48 meeting the AC of whom no tumor samples were available) were screened
      for small mutations. In 134 index patients, a pathogenic MSH2 mutation, and in
      118 patients, a pathogenic MLH1 mutation was identified (overall detection rate
      for pathogenic mutations 56%). One hundred sixty distinct mutations were
      detected, of which 86 are novel mutations. Noteworthy is that 2 mutations were
      over-represented in our patient series: MSH2,c.942+3A>T and MLH1,c.1489_1490insC,
      which account for 11% and 18% of the MSH2 and MLH1 mutations, respectively. A
      subset of 238 patients was screened for large genomic deletions. In 24 (10%)
      patients, a deletion was found. In 72 patients, only unspecified variants were
      found. Our findings demonstrate that preselection by microsatellite analysis
      substantially raises mutation detection rates in patients not meeting the AC. As
      a mutation detection strategy for German HNPCC patients, we recommend to start
      with screening for large genomic deletions and to continue by screening for
      common mutations in exon 5 of MSH2 and exon 13 of MLH1 before searching for small
      mutations in the remaining exons.

PMID- 15849734
TI  - Multislice CT to evaluate coronary stent patency: a case report.
AB  - This is a case report on the ability of 16-slice computed tomography in assessing
      the patency of coronary stent and diagnosing an asymptomatic stenotic lesion with
      soft plaque morphology. These findings were confirmed with a selective coronary
      angiography. Identification of lesion morphology facilitated our decision on
      prophylactic and direct stenting to the lesion.

PMID- 15849735
TI  - Enhanced gene expression in the forebrain of hatchling and juvenile male zebra
      finches.
AB  - The molecular mechanisms regulating sexual differentiation of the brain are
      largely unknown, although progress is being made, particularly in some mammalian
      systems. To uncover more of the key factors, a screen was conducted for genes
      involved in sexually dimorphic development of the neural song system in zebra
      finches. cDNA microarrays were initially used to compare gene expression in the
      telencephalons of hatchling and juvenile males and females. Then, real-time
      quantitative polymerase chain reaction (PCR) was employed to confirm sex
      differences, and the brain regions expressing the cDNAs of interest were
      localized using in situ hybridization. Several genes, including those likely to
      encode two ribosomal proteins (RPL17 and RPL37), SCAMP1, ZNF216, and a COBW
      domain containing protein, showed enhanced expression in the telencephalon of
      males compared to females. In several cases, expression in the song control
      nuclei specifically was detected only in males. Interestingly, the sequences of
      some of these cDNAs shared substantial homology with regions of the chicken Z
      chromosome (male birds are ZZ, females ZW). Thus, we have identified genes likely
      to be involved in masculinization of the structure and/or function of the song
      circuit, some of which could be initial triggers for the sexual differentiation
      process.

PMID- 15849736
TI  - A splice variant of the Drosophila vesicular monoamine transporter contains a
      conserved trafficking domain and functions in the storage of dopamine, serotonin,
      and octopamine.
AB  - Vesicular monoamine transporters (VMATs) mediate the transport of dopamine (DA),
      serotonin (5HT), and other monoamines into secretory vesicles. The regulation of
      mammalian VMAT and the related vesicular acetylcholine transporter (VAChT) has
      been proposed to involve membrane trafficking, but the mechanisms remain unclear.
      To facilitate a genetic analysis of vesicular transporter function and
      regulation, we have cloned the Drosophila homolog of the vesicular monoamine
      transporter (dVMAT). We identify two mRNA splice variants (DVMAT-A and B) that
      differ at their C-terminus, the domain responsible for endocytosis of mammalian
      VMAT and VAChT. DVMAT-A contains trafficking motifs conserved in mammals but not
      C. elegans, and internalization assays indicate that the DVMAT-A C-terminus is
      involved in endocytosis. DVMAT-B contains a divergent C-terminal domain and is
      less efficiently internalized from the cell surface. Using in vitro transport
      assays, we show that DVMAT-A recognizes DA, 5HT, octopamine, tyramine, and
      histamine as substrates, and similar to mammalian VMAT homologs, is inhibited by
      the drug reserpine and the environmental toxins 2,2,4,5,6-pentachlorobiphenyl and
      heptachlor. We have developed a specific antiserum to DVMAT-A, and find that it
      localizes to dopaminergic and serotonergic neurons as well as octopaminergic,
      type II terminals at the neuromuscular junction. Surprisingly, DVMAT-A is co
      expressed at type II terminals with the Drosophila vesicular glutamate
      transporter. Our data suggest that DVMAT-A functions as a vesicular transporter
      for DA, 5HT, and octopamine in vivo, and will provide a powerful invertebrate
      model for the study of transporter trafficking and regulation.

PMID- 15849737
TI  - Phospholipase A(2) activity of beta-bungarotoxin is essential for induction of
      cytotoxicity on cerebellar granule neurons.
AB  - The aim of this study was to investigate the mechanism of the cytotoxic effect of
      beta-bungarotoxin (beta-BuTX), a presynaptic neurotoxin, on rat cerebellar
      granule neurons (CGNs). The maturation of CGNs is characterized by the prominent
      dense neurite networks that became fragmented after treatment with beta-BuTX, and
      this cytotoxic effect of beta-BuTX on CGNs was in a dose- and time-dependant
      manner. The cytotoxic effect of beta-BuTX was found to be more potent than other
      toxins, such as alpha-BuTX, cardiotoxin, melittin, and Naja naja atra venom
      phospholipase A(2). Meanwhile, undifferentiated neuroblastoma neuronal cell
      lines, IMR-32 and SK-N-MC, and astrocytes were found to be resistant to beta
      BuTX. These results indicated that only the mature CGNs were sensitive to beta
      BuTX insults. None of the following chemicals: antioxidants, K(+)-channel
      activator, K(+)-channel antagonists, intracellular Ca(2+) chelator, Ca(2+)
      channel blockers, NMDA receptor antagonists, and nitric oxide synthase inhibitor
      tested, were able to reduce beta-BuTX-induced cytotoxicity. However, secretory
      type phospholipase A(2) inhibitors (glycyrrhizin and aristolochic acid) and a
      free radical scavenger (5,5-dimethyl pyrroline N-oxide, DMPO) could attenuate not
      only beta-BuTX-induced cytotoxicity but also ROS production and caspase-3
      activation. These data suggest that phospholipase A(2) activity of beta-BuTX may
      be responsible for free radical generation and caspase-3 activation that accounts
      for the observed cytotoxic effect. It is proposed that the CGNs can be a useful
      tool for studying interactions of the molecules on neuronal plasma membrane with
      beta-BuTX that mediates the specific cytotoxicity.

PMID- 15849738
TI  - Receptor activator of NF-kappaB ligand protein expression in UMR-106 cells is
      differentially regulated by parathyroid hormone and calcitriol.
AB  - Expression of the cytokine, receptor activator of NF-kappaB ligand (RANKL), is
      stimulated by both parathyroid hormone (PTH) and calcitriol in osteoblasts. Most
      studies have examined the effects on RANKL mRNA, and less information is
      available on the protein products. We have determined the effects of PTH, the
      adenylate cyclase stimulator forskolin, and calcitriol, alone and in combination,
      on endogenous RANKL protein expression in UMR-106 rat osteoblastic osteosarcoma
      cells by Western blotting and enzyme immunoassay (EIA). PTH and forskolin dose
      dependently increased a approximately 52 kDa band in whole cell lysates that was
      detected by both C- and N-terminal directed RANKL antibodies. Calcitriol
      treatment produced little or no expression of this approximately 52 kDa band, but
      markedly increased the expression of a approximately 32 kDa band that was only
      detected with an antibody directed to the N-terminus of RANKL. An EIA based on
      RANKL binding to OPG detected a large increase in RANKL expression following
      calcitriol treatment, and much smaller increases with PTH or forskolin. The
      combination of PTH and calcitriol or forskolin and calcitriol elicited effects
      similar to those of PTH and forskolin alone, as detected by both Western blotting
      and EIA. In contrast to the effects on protein, all agents increased RANKL mRNA
      expression, with the greatest effects seen with the co-treatments. The results
      indicate that PTH, likely through effects on cyclic AMP, has a different effect
      on RANKL processing than calcitriol. The approximately 52 and approximately 32
      kDa RANKL products appear to interact differently with OPG, which could affect
      responses to the agents in target cells.

PMID- 15849739
TI  - Risk assessment of dietary exposure to pesticides using a Bayesian method.
AB  - Risk assessment of pesticides can be a statistically difficult problem because
      pesticides occur only occasionally, but they may occur on multiple components in
      the diet. A Bayesian statistical model is presented which incorporates
      multivariate modelling of food consumption and modelling of pesticide
      measurements which are for a large part below a measurement threshold. It is
      shown that Bayesian modelling is feasible for a limited number of food
      components, and that in a data-rich situation the model compares well with an
      empirical Monte Carlo modelling.

PMID- 15849740
TI  - Initiating morphological changes associated with long-term facilitation in
      Aplysia is independent of transcription or translation in the cell body.
AB  - In Aplysia, the growth of axonal arbor and the formation of new presynaptic
      varicosities are thought to contribute to long-term facilitation (LTF) produced
      by serotonin (5-HT). While it is known that there is a requirement for both
      transcription and translation in LTF and in the accompanying morphological
      changes, the mechanisms mediating the initiation and maintenance of these changes
      are poorly understood. We used long-term labeling of the presynaptic sensory
      neuron to carry out repeated imaging of axonal morphology, coupled with
      electrophysiology, to further elucidate the macromolecular requirements of this
      process. Robust synaptic facilitation, axonal growth, and the formation of axonal
      varicosities were elicited by 5-HT even when transcription was blocked with
      actinomycin. Increases in synaptic efficacy and varicosity number were detected
      12 h after exposure to 5-HT but did not persist to 24 h. Even when sensory neuron
      cell bodies were removed, eliminating the contributions of both somal
      transcription and translation, 5-HT elicited these transient morphological and
      electrophysiological responses. New sensory varicosities contacting the
      postsynaptic neuron were filled with the neuropeptide sensorin. Under all
      conditions, global inhibition of protein synthesis completely blocked the
      formation of new axonal branches and varicosities. These results demonstrate that
      neither transcription nor somal translation is required to initiate the axonal
      growth that often accompanies long-term synaptic plasticity-protein synthesis in
      the axon is sufficient. Macromolecular synthesis in the cell body is, however,
      required to maintain the enlarged arbor.

PMID- 15849741
TI  - Sulindac corrects defective apoptosis and suppresses azoxymethane-induced colonic
      oncogenesis in p53 knockout mice.
AB  - The acute apoptotic response to genotoxic carcinogens (AARGC) might be important
      for controlling the subsequent colonic mutational load and progression through
      oncogenesis. We have found previously that AARGC is p53-dependent with a gene
      dosage effect, and that decreased AARGC in p53(+/-) and p53(-/-) mice is
      associated with increased susceptibility to carcinogen-induced oncogenesis. We
      tested the ability of sulindac to reverse these defects. The effect of sulindac
      on azoxymethane (AOM)-induced apoptosis was measured in colonic epithelium in
      wild-type, p53(+/-) and p53(-/-) mice, 8 hr after a single AOM injection.
      Sulindac supplementation (0.5 +/- 0.1 mg/day) restored defective AARGC in p53(+/
      ) but not in p53(-/-) mice. For effect on colon tumor development, sulindac
      treatment was started at age 4 weeks in wild-type, p53(+/-) and p53(-/-) mice;
      three weekly AOM injections were commenced at 6 weeks of age to induce tumors.
      Sulindac reduced significantly tumor incidence and multiplicity in wild-type mice
      (17% and 0.3 tumors/mouse compared to 36% and 0.8 respectively without drug), in
      p53(+/-)mice (38% and 0.8 compared to 64% and 1.63) and in p53(-/-) mice (63% and
      1.0 compared to 90% and 1.74). Although loss of p53 function impairs the
      apoptotic response to AOM-induced DNA damage, sulindac is capable of partly
      restoring this defect. As sulindac also reverses the increased risk of
      oncogenesis due to p53 dysfunction, its enhancement of the apoptotic response to
      initiating mutations might act to reduce mutational load driving oncogenesis.
      Sulindac is an effective chemopreventive agent in the presence of p53
      dysfunction.

PMID- 15849742
TI  - P73 functionally replaces p53 in Adriamycin-treated, p53-deficient breast cancer
      cells.
AB  - p53-Related genes, p73 and p63, encode 2 classes of proteins, TA-p73/p63 and
      DeltaN-p73/p63. TA-p73/p63 demonstrate p53-like properties including gene
      transactivation and cell death promotion, whereas DeltaN-p73/p63 lack these p53
      like functions. Although p53-deficient cancer cells are often less responsive to
      chemotherapy, they are not completely drug resistant, suggesting that other
      apoptotic pathways are at work. Here, we compared for the first time to our
      knowledge p73 and p63 activation in various breast cancer (BC) cell lines after
      Adriamycin (ADR) treatment, an agent considered as mandatory in breast cancer
      chemotherapy. Our study was carried out using 1 p53-proficient BC cell line (MCF7
      cells) and 3 BC cell lines deficient in p53 response (MCF7/ADR(IGR), MDA-MB157
      and T47D) after ADR-induced genotoxic stress. We report that in cells with no p53
      response after ADR treatment, TAp73, but not TAp63 or DeltaN-p73/p63, may replace
      p53 in triggering not only apoptosis but also cell cycle arrest or DNA repair
      effectors such as p21, GADD45, 14-3-3sigma and p53R2. We also demonstrate that
      TAp73 siRNA inhibits the accumulation of TAp73 in response to ADR treatment in
      MDA-MB157 cells and confers protection against ADR. ADR-induced downregulation of
      the DeltaNp73 isoform in the T47D cell line with nonfunctional mutant p53 further
      supports anti-apoptotic function of the isoform antagonistic to both p53 and TA
      p73/p63. Exogenous TAp73 and DeltaNp73 overexpression in p53-response-deficient
      cell lines further confirms these results. cDNA microarray techniques
      demonstrated that the cellular response induced by p73 during ADR treatment could
      involve specific genes.

PMID- 15849743
TI  - Microenvironmental influences on mutagenesis in mammary epithelial cells.
AB  - Tumor progression may be viewed as an evolutionary process at the cellular level.
      Because blood supply to solid tumors is inadequate, the cancer cells face a
      hostile microenvironment characterized by hypoxia or anoxia, acidic extracellular
      pH and nutrient deficiencies. It has been proposed that these factors result in
      increased levels of spontaneous mutagenesis and thereby contribute to tumor
      progression. We have examined spontaneous mutagenesis in vitro and in vivo, using
      previously characterized cell lines (mammary epithelial cells [ME] and mammary
      fibroblast cells [MFib]) from the mammary gland of the BigBluetrade mark rat,
      carrying a transgene construct suitable for the detection of mutations. Cells
      were exposed in vitro to control conditions, low pH, or to glucose deprivation,
      under normoxic or hypoxic culture conditions, and were also grown as xenografted
      tumors in immune-deficient mice. We examined cell survival and mutant
      frequency/spectrum at the cII locus. Significant increases in mutant frequency
      were observed in ME cells exposed to hypoxia alone or in combination with no
      glucose; the latter condition also resulted in reduced clonogenic survival. Cells
      grown as xenografts and then recovered and expanded in culture also had elevated
      frequencies of spontaneous mutations. We observed a shift in the spontaneous
      mutation spectrum between the ME cells and the MET cells (cultured in vitro or
      isolated from mouse xenograft tumors). These results support the concept that the
      tumor microenvironment contributes to tumor progression by enhancing spontaneous
      mutagenesis, that different cell types from the same organ can respond
      differently to these stresses and that differences in microenvironment may
      influence the types of mutations that arise.

PMID- 15849744
TI  - Loss of heterozygosity of 1p in uveal melanomas with monosomy 3.
AB  - Gains and losses of chromosomes 1, 3, 6 and 8 are nonrandom chromosomal
      aberrations in uveal melanoma. Monosomy 3 is the most frequent abnormality and is
      associated with poor prognosis. To identify regions of allelic loss on the short
      arm of chromosome 1 and to investigate if these alterations contribute to uveal
      melanoma progression, we performed microsatellite analysis of 10 loci in 70 uveal
      melanomas. A total of 51 tumors were obtained from patients with clinical follow
      up data, 19 tumors were from recent patients without follow-up. Loss of
      heterozygosity (LOH) of at least 1 marker was more frequent in tumors with
      monosomy 3 (40%) than in tumors with disomy 3 (10%). In particular, loss of the
      entire short arm of chromosome 1 was only observed in tumors with monosomy 3 (p =
      0.0001). By comparing the extent of 1p LOH in all tumors with monosomy 3, we were
      able to define a smallest region of overlap (SRO) of approximately 55 Mb, which
      is flanked by markers D1S507 and D1S198. On the basis of our data and published
      cytogenetic data, we propose that 1p31 harbors genes involved in the progression
      of uveal melanoma with monosomy 3.

PMID- 15849745
TI  - Alteration of AKAP220, an upstream component of the Rb pathway, in oral
      carcinogenesis.
AB  - Few genes have been implicated in the development of oral cancer. In our study,
      we identified a novel gene in the Rb pathway that is frequently altered and
      overexpressed in oral tumors. Significantly, the alteration is also associated
      with early oral premalignant lesions (OPLs). This region was identified through a
      genomewide scan using randomly amplified polymorphic DNA (RAPD) PCR of 40
      microdissected oral squamous cell carcinomas (SCCs). Recurrent gain of a
      approximately 400 bp signal was observed in multiple patients. This gain was
      localized to 13q14.11, a region frequently altered in multiple cancer types.
      Through microsatellite analysis, a 1.9 Mbp minimal region of alteration (MRA) was
      defined between D13S263 and D13S1227. Allelic imbalance (AI) in the MRA was
      present in only 28% of low-grade dysplasia, but strikingly increased with
      progression to 64% in high-grade dysplasia, plateauing at 61% in tumors, thus
      implicating this alteration in the early stages of disease development. Of the 3
      genes residing within the MRA, Receptor Activator of NK-kappa-B Ligand (RANKL)
      and Diacylglycerol Kinase (DGKH) showed no change in expression levels in tumors
      compared to normal tissue. In contrast, 12 of 16 tumors showed significant
      overexpression of A-Kinase Anchoring Protein 220 (AKAP220). Since AKAP220 plays a
      role in regulating the Rb pathway, its dysregulation may contribute significantly
      to alterations in cell cycle regulation that facilitate progression of OPLs.

PMID- 15849746
TI  - The inhibitory effect of flaxseed on the growth and metastasis of estrogen
      receptor negative human breast cancer xenograftsis attributed to both its lignan
      and oil components.
AB  - Our previous studies have shown that dietary flaxseed (FS) can reduce the growth
      and metastasis of human estrogen receptor negative (ER-) breast cancer in nude
      mice. The aims of our study were to determine (i) whether the tumor inhibitory
      effect of FS was due to its oil (FO), lignan secoisolariciresinol diglycoside
      (SDG), or both components, and (ii) whether the effect on tumor growth was
      related to increased lipid peroxidation. Athymic nude mice were orthotopically
      injected with ER- breast cancer cells (MDA-MB-435) and 8 weeks later were fed
      either the basal diet (BD) or BD supplemented with 10% FS, SDG, FO, or combined
      SDG and FO (SDG + FO) for 6 weeks. The SDG and FO levels were equivalent to the
      amounts in the 10% FS. Compared to the BD group, the tumor growth rate was
      significantly lower (p < 0.05) in the FS, FO, and SDG + FO groups, in concordance
      with decreased cell proliferation and increased apoptosis; however, these did not
      significantly relate to the lipid peroxidation, indexed as malonaldehyde (MDA),
      in the primary tumors. Lung metastasis incidence was reduced (16-70%) by all
      treatments, significantly in the FS and SDG + FO groups. The distant lymph node
      metastasis was significantly decreased (52%) only in the FO group. Although the
      total metastasis incidence was lowered (42%) significantly only in the SDG + FO
      group, all treatment groups did not differ significantly. In conclusion, FS
      reduced the growth and metastasis of established ER- human breast cancer in part
      due to its lignan and FO components, and not to lipid peroxidation.

PMID- 15849747
TI  - Geographic pathology revisited: development of an atlas of cancer in India.
AB  - Information on 217,174 microscopically diagnosed cancers diagnosed in 2001-2002
      was collected from pathology laboratories in 68 districts across India. Data
      collection took place primarily via the Internet. Average annual age-adjusted
      incidence rates for microscopically diagnosed cases (MAAR) by gender and site
      were calculated for each of the 593 districts in the country. The rates were
      compared to those from established population based cancer registries (PBCR). In
      82 districts, the MAAR for 'all cancer sites' was above a "completeness"
      threshold of 36.2/100,000 (based on results of a rural PBCR). The results
      confirmed some known features of the geography of cancer in India, and brought to
      light new ones. Cancers of the mouth and tongue are particularly frequent in both
      genders in the southern states. Very high rates of nasopharynx cancer were found
      in the northeastern states (Nagaland, Manipur). There was clear geographic
      correlation between the rates of cervical and penile cancer, and a high rate of
      stomach and lung cancer (in both genders) in many districts of Mizoram State. The
      area of high risk for gallbladder cancer seems larger than suspected previously,
      involving a wide band of northern India. There is a belt of high incidence of
      thyroid cancer in females in southwest coastal districts. Other than identifying
      possible existence of high-risk areas of specific cancers, our study has
      recognized places where PBCR could be established. The study was remarkably cost
      effective and the electronic data-capture methodology provides a model for health
      informatics in the setting of a developing country.

PMID- 15849748
TI  - Accuracy of human papillomavirus testing in primary screening of cervical
      neoplasia: results from a multicenter study in India.

PMID- 15849749
TI  - Interventional study in 1,232 young German children to prevent the development of
      melanocytic nevi failed to change sun exposure and sun protective behavior.
AB  - Sunscreens have been proposed as protective measures to inhibit the development
      of melanocytic nevi in childhood and to decrease the long term risk for cutaneous
      melanoma development. Our present study investigates the influence of sunscreen
      use and education on the number of incident melanocytic nevi. A total of 1,812
      children in 78 public nursery schools in 2 German cities were randomized to 3
      study arms: (i) parents were informed on study purpose and sun protection
      measures only at an initial educational meeting; (ii) parents received
      educational material 3 times yearly; and (iii) education and 800 ml free broad
      spectrum sunscreens with sun protection factor 25 provided on a yearly basis.
      Final assessment after 3 years follow-up included 1,232 children (68%). Changes
      of sun protection habits including sunscreen use were sparse, without any
      differences attributable to the intervention efforts. As a consequence, there
      were no significant differences between the 3 study arms for the main outcome
      measure, the number of incident melanocytic nevi. Analysis of the sunscreen use
      in the entire cohort irrespective of our study arms did not show any impact on
      incident nevus numbers in bivariate or multivariate analysis. In conclusion,
      intervention with educational letters and free sunscreens seemingly had no
      additional effect on sun-protection for German children. High prevalence of
      sunscreen use at study commencement, social desirability, and inadequate
      application of sunscreens might have partially covered their effect.

PMID- 15849750
TI  - Aberrant promoter methylation of p16(INK4a), RARB2 and SEMA3B in bronchial
      aspirates from patients with suspected lung cancer.
AB  - Aberrant promoter methylation of normally unmethylated CpG-islands offers a
      promising tool for the development of molecular biomarkers. We investigated
      bronchial aspirates of patients admitted for suspected lung cancer with regard to
      the prevalence of aberrant methylation of potential marker genes. Applying
      quantitative methylation specific PCR (QMSP) we analyzed bronchial aspirates from
      75 patients with primary lung cancer and 64 bronchial aspirates of patients
      diagnosed with benign lung disease for promoter methylation of 3 candidate marker
      genes (p16(INK4a), RARB2 and SEMA3B). Hypermethylation of p16(INK4a) detected
      18/75 (24%) cases with primary lung cancer and was present predominantly in
      squamous cell carcinomas (14/25; 56%). RARB2 QMSP at an assay threshold greater
      than 30 was found in 42/75 (56%) patients with lung cancer without relation to
      histological subtype. Patients with benign lung disease showed methylation of
      p16(INK4a) and a RARB2 QMSP at an assay threshold greater than 30 in 0/64 (0%)
      and 8/64 (13%) cases, respectively. Combining the 2 methylation markers,
      p16(INK4a) and RARB2, yielded a sensitivity of 69% and a specificity of 87% for
      the diagnosis of pulmonary malignancy. In contrast, SEMA3B displayed frequent
      promoter methylation (around 90%) both in bronchial aspirates of tumor and
      nontumor cases and thus was not suited as a biomarker. The results of this study
      indicate that QMSP analysis of p16(INK4a) and RARB2 may aid the diagnosis of
      primary lung cancer in bronchial aspirates. In particular, detection of
      p16(INK4a) methylation by QMSP may serve as a highly specific marker of pulmonary
      squamous cell carcinoma.

PMID- 15849751
TI  - MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both
      processes are stimulated by probenecid.
AB  - ATP binding cassette (ABC) multidrug transporters such as P-glycoprotein (P-gp,
      ABCB1) and BCRP (ABCG2) confer resistance against anticancer drugs and can limit
      their oral availability, thus contributing to failure of chemotherapy. Like P-gp
      and BCRP, another ABC transporter, MRP2 (ABCC2), is found in apical membranes of
      pharmacologically important epithelial barriers and in a variety of tumors. MRP2
      transports several anticancer drugs and might thus have a similar impact on
      chemotherapy as P-gp and BCRP. We here show that human MRP2 transduced into
      epithelial MDCKII cells efficiently transported the taxane anticancer drugs
      paclitaxel and docetaxel and that this transport could be substantially
      stimulated with the drug probenecid, a representative of a range of MRP2
      stimulating drugs. Transport of 2 previously identified MRP2 substrates,
      etoposide and vinblastine, was likewise stimulated by probenecid. MRP2 further
      conferred substantial resistance against paclitaxel toxicity, and this resistance
      was 2.7-fold stimulated by probenecid. Our data indicate that MRP2 function might
      affect chemotherapy with taxanes, potentially influencing both tumor resistance
      and taxane pharmacokinetics. Moreover, coadministration of probenecid and other
      MRP2-stimulating drugs might lead to unforeseen drug-drug interactions by
      stimulating MRP2 function, potentially leading to suboptimal levels of taxanes
      and other anticancer drugs in plasma and tumor.

PMID- 15849752
TI  - Association of hereditary hemorrhagic telangiectasia and hereditary nonpolyposis
      colorectal cancer in the same kindred.
AB  - Endoglin (CD105) is a proliferation-associated protein that is strongly expressed
      in endothelial tissue and has a role in tumor angiogenesis. Mutations in endoglin
      are also linked to Hereditary Hemorrhagic Telangiectasia type 1 (HHT1), an
      autosomal dominant disease associated with aberrant angiogenesis. We report an
      unusual association of HHT1 and Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
      in the same kindred. Genetic analysis indicates that these 2 syndromes are
      genetically unrelated and separately segregated within the family. The mutation
      in the endoglin gene leads to a truncated protein. The mutation in the mismatch
      repair gene MLH1 causes a splicing defect, giving synthesis to an unstable mRNA
      from this mutated allele. The potential protective role of an endoglin mutation
      in patients with HNPCC is discussed.

PMID- 15849753
TI  - 2-5A induces a conformational change in the ankyrin-repeat domain of RNase L.
AB  - RNase L is responsible for the 2-5A host defense system, an RNA degradation
      pathway present in cells of higher vertebrates that functions in both the
      antiviral and anticellular activities of interferon. The activity of RNase L is
      tightly regulated and is exerted only in the presence of 2-5A. The postulated
      mechanism of its regulation is as follows: the N-terminal half ankyrin-repeat
      domain masks the C-terminal half nuclease domain in the absence of 2-5A. On
      binding 2-5A at the ankyrin-repeat domain, RNase L forms a homodimer and removes
      the ankyrin-repeat domain from the nuclease domain to become the active form. A
      conformational change in the ankyrin-repeat domain is a key step in this
      hypothetical mechanism, but there is as yet no evidence for such a change. To
      clarify the events induced by 2-5A binding, we established procedures for
      expression and purification of the ankyrin-repeat domain of human RNase L.
      Fluorescence spectra of the protein showed clear difference in the presence and
      absence of 2-5A. The alterations in the spectra supported conformational changes
      of the protein. Time-resolved anisotropy measurements indicated that 2-5A binding
      led to a significant decrease in the rotational radius of the protein. In
      addition, 2-5A provided the domain with resistance to protease digestion as a
      result of a conformational change. These results indicated that the ankyrin
      repeat domain of RNase L constricts its structure by binding of 2-5A. This
      observation suggests a revised model of the 2-5A-induced activation of RNase L.

PMID- 15849754
TI  - Universal biases in protein composition of model prokaryotes.
AB  - The levels of cellular organization in living organisms are the results of a
      variety of selection pressures. We have investigated here the final outcome of
      this integrated selective process in proteins of the best known microbial models
      Escherichia coli, Bacillus subtilis, and Methanococcus jannaschii, supposed to
      have undergone separate evolution for more than 1 billion years. Using
      multivariate analysis methods, including correspondence analysis, we studied the
      overall amino acid composition of all proteins making a proteome. Starting from
      and further developing previous results that had pointed out some general forces
      driving the amino acid composition of the proteomes of these model bacteria, we
      explored the correlations existing between the structure and functions of the
      proteins forming a proteome and their amino acid composition. The electric charge
      of amino acids measured against hydrophobicity creates a highly homogeneous
      cluster, made exclusively of proteins that are core components of the cytoplasmic
      membrane of the cell (integral inner membrane proteins). A second bias is imposed
      by the G+C content of the genome, indicating that protein functions are so robust
      with respect to amino acid changes that they can accommodate a large shift in the
      nucleotide content of the genome. A remarkable role of aromatic amino acids was
      uncovered. Expressed orphan proteins are enriched in these residues, suggesting
      that they might participate in a process of gain of function during evolution.

PMID- 15849755
TI  - Rapid assessment of contact-dependent secondary structure propensity: relevance
      to amyloidogenic sequences.
AB  - We have previously demonstrated that calculation of contact-dependent secondary
      structure propensity (CSSP) is highly sensitive in detecting non-native beta
      strand propensities in the core sequences of known amyloidogenic proteins. Here
      we describe a CSSP method based on an artificial neural network that rapidly and
      accurately quantifies the influence of tertiary contacts (TCs) on secondary
      structure propensity in local regions of protein sequences. The present method
      exhibited 72% accuracy in predicting the alternate secondary structure adopted by
      chameleon sequences located in highly disparate TC regions. Analysis of 1930
      nonhomologous protein domains reveals that the alpha-helix and the beta-strand
      largely share the same sequence context, and that tertiary context is a major
      determinant of the native conformation. Conversely, it appears that the
      propensity of random coils for either the alpha-helix or the beta-strand is
      largely invariant to tertiary effects. The present CSSP method successfully
      reproduced the amyloidogenic character observed in local regions of the human
      islet amyloid polypeptide (hIAPP). Furthermore, CSSP profiles were strongly
      correlated (r = 0.76) with the observed mutational effects on the aggregation
      rate of acylphosphatase. Taken together, these results provide compelling
      evidence in support of the present CSSP approach as a sensitive probe useful for
      analysis of full-length proteins and for detection of core sequences that may
      trigger amyloid fibril formation. The combined speed and simplicity of the CSSP
      method lends itself to proteome-wide analysis of the amyloidogenic nature of
      common proteins.

PMID- 15849756
TI  - Geometric cooperativity and anticooperativity of three-body interactions in
      native proteins.
AB  - Characterizing multibody interactions of hydrophobic, polar, and ionizable
      residues in protein is important for understanding the stability of protein
      structures. We introduce a geometric model for quantifying 3-body interactions in
      native proteins. With this model, empirical propensity values for many types of 3
      body interactions can be reliably estimated from a database of native protein
      structures, despite the overwhelming presence of pairwise contacts. In addition,
      we define a nonadditive coefficient that characterizes cooperativity and
      anticooperativity of residue interactions in native proteins by measuring the
      deviation of 3-body interactions from 3 independent pairwise interactions. It
      compares the 3-body propensity value from what would be expected if only pairwise
      interactions were considered, and highlights the distinction of propensity and
      cooperativity of 3-body interaction. Based on the geometric model, and what can
      be inferred from statistical analysis of such a model, we find that hydrophobic
      interactions and hydrogen-bonding interactions make nonadditive contributions to
      protein stability, but the nonadditive nature depends on whether such
      interactions are located in the protein interior or on the protein surface. When
      located in the interior, many hydrophobic interactions such as those involving
      alkyl residues are anticooperative. Salt-bridge and regular hydrogen-bonding
      interactions, such as those involving ionizable residues and polar residues, are
      cooperative. When located on the protein surface, these salt-bridge and regular
      hydrogen-bonding interactions are anticooperative, and hydrophobic interactions
      involving alkyl residues become cooperative. We show with examples that
      incorporating 3-body interactions improves discrimination of protein native
      structures against decoy conformations. In addition, analysis of cooperative 3
      body interaction may reveal spatial motifs that can suggest specific protein
      functions.

PMID- 15849757
TI  - Von Willebrand factor antigen levels in Behcet disease.
AB  - High von Willebrand factor antigen (vWF:Ag) levels can be found due to vascular
      endothelial injury in Behcet disease. The aim of this study is to evaluate
      whether there is any relationship between vWF:Ag levels and vascular or other
      organ involvements and acute-phase reactants in Behcet disease. Fifteen controls
      and 17 Behcet's patients were included; 10 had oral ulcers, 5 had genital ulcers,
      3 had skin lesions, 6 had ocular involvement, 5 had arthritis, and 6 had vascular
      involvement. VWF:Ag levels were higher in Behcet's patients than controls. VWF:Ag
      levels in Behcet's patients with oral ulcers, genital ulcers, and ocular and
      vascular involvement were statistically higher than in the control group.
      Differences between vWF:Ag levels in Behcet's patients with and without organ
      involvement were not statistically significant. A linear correlation between
      serum ferritin levels and vWF:Ag levels was observed. These results demonstrate
      that elevated levels of plasma vWF:Ag are related to Behcet disease exacerbation
      rather than vascular involvement.

PMID- 15849758
TI  - Unusual extramedullary relapses under imatinib mesylate treatment in chronic
      myeloid leukemia.

PMID- 15849759
TI  - Chronic parvovirus infection and G6PD deficiency masquerading as Diamond-Blackfan
      anemia.
AB  - Bone marrow aplasia due to parvovirus B19 infections is usually mild and self
      limited. In patients with hereditary or acquired hemolytic anemias, B19 infection
      can cause a severe and life-threatening anemia due to the shortened half-life of
      red cells, but here, too, the transient nature of the infection soon remits the
      symptoms. Chronic infections with parvovirus are more characteristically
      associated with immunodeficiency states. We report here a case of B19-induced
      anemia in a patient with G6PD deficiency and hypogammaglobulinemia which was
      mislabeled as Diamond-Blackfan anemia until the use of modern laboratory
      techniques allowed a correct diagnosis to be made.

PMID- 15849760
TI  - Bone marrow embolism in sickle cell disease: a review.
AB  - The fat embolism syndrome is an important complication of patients with sickle
      cell hemoglobinopathies because of severe morbidity and mortality. Our recent
      experience with three cases that survived with intensive supportive care and
      prompt use of transfusion stimulates this review. A high index of suspicion,
      prompt use of diagnostic tools, and aggressive clinical management are the keys
      to a successful outcome.

PMID- 15849761
TI  - Prevalence and risk factors for heart disease among males with hemophilia.
AB  - There have been conflicting reports in the literature about the protective effect
      of hemophilia on the occurrence of ischemic heart disease (IHD). Circulatory
      disease has been reported as the second most common cause of death in persons
      with hemophilia in the United States. In addition to diabetes and hypertension,
      high levels of FVIII, as may occur during factor concentrate infusions, may
      increase IHD risk in this population. To estimate the prevalence of heart disease
      and examine factors associated with IHD and other heart diseases among persons
      with hemophilia, we analyzed data collected from the medical records of 3,422
      males with hemophilia living in six U.S. states from 1993 to 1998. Heart disease
      cases were ascertained from among 2,075 persons who were hospitalized at least
      once during the 6-year period. Of these, 48 were diagnosed with IHD and 106, with
      other types of heart disease. The age-specific prevalence of IHD ranged from
      0.05% in those under 30 years to 15.2% in those 60 years or older. Hospital
      discharge rates in males with hemophilia with IHD and other types of heart
      disease were lower compared to rates in age-matched U.S. males. In our cohort, as
      in the general population, IHD was independently associated with age,
      hypertension, diabetes, and hyperlipidemia. Other heart diseases were associated
      with HIV infection, hypertension, hemophilia B, and diabetes. In summary, persons
      with hemophilia have unique risk factors such as infusion of factor concentrates
      and infection with HIV that may predispose them to heart disease as their life
      expectancy increases.

PMID- 15849762
TI  - Severe pulmonary arterial hypertension as initial manifestation of intravascular
      lymphoma: case report.
AB  - Intravascular lymphoma (IVL) is a rare and usually fatal disease that belongs to
      the class of high-grade malignant lymphomas and which is characterized by
      proliferation of neoplastic lymphoid cells exclusively within the lumina of small
      blood vessels. Its polymorphic and nonspecific clinical manifestations make
      antemortem diagnosis very difficult. We report herein a case of IVL revealed by
      fatal, precapillary, pulmonary arterial hypertension and associated with long
      lasting fever. Extensive investigation of the usual causes of pulmonary arterial
      hypertension was negative. The diagnosis of intravascular lymphoma was made on
      postmortem analysis, revealing diffuse and sometimes complete obliterations of
      the lumina of small blood vessels by large B-cell lymphoma, including pulmonary
      capillaries. Thus, we propose that IVL must be added to the spectrum of
      etiologies of subacute pulmonary arterial hypertension, notably in the context of
      associated fever, both entities requiring emergency diagnosis. For this purpose,
      blood collected via pulmonary capillary-wedge aspiration for cytologic
      examination may be associated with right-sided heart catheterization when this
      latter procedure is suitable.

PMID- 15849763
TI  - Not all Noni liquid dietary supplements are created equal.

PMID- 15849764
TI  - Acquired hemophilia in a patient affected by acute myeloid leukemia.

PMID- 15849765
TI  - Granulocytic sarcoma presenting as bilateral adrenal masses.
AB  - Granulocytic sarcoma (GS) is a collection of immature myeloid cells contained
      outside the bone marrow often seen in association with acute myeloid leukemia or
      as a sign of leukemic transformation in myeloproliferative disorders. Rarely, GS
      is an isolated finding unaccompanied by another hematological disorder. GS can
      occur at a variety of sites, most commonly involving the bone, soft tissue, lymph
      nodes, or skin. We report GS presenting as bilateral adrenal masses in a patient
      without an antecedent hematologic illness.

PMID- 15849766
TI  - High-altitude trekking in the Himalayas increases the activity of circulating
      endothelial cells.
AB  - Circulating endothelial progenitor cells (EPCs) are believed to contribute to
      vascular homeostasis; unfortunately, the response of EPCs in physiological
      conditions remains largely unknown. Herein we report our observations of a 44
      year-old healthy subject after a trek in the Himalayas that support high-altitude
      hypoxia and exercise oxygen demands are strong stimuli for clonogenic endothelial
      cell activation and activity, as shown by the increase in the number of mature
      EPCs and in the endothelial colony-forming unit capacity. Both of these effects
      were completely reverted at sea level, 45 days after the subject's trek.

PMID- 15849767
TI  - Successful use of recombinant factor VIIa for emergency fasciotomy in a patient
      with hemophilia A and high-titer inhibitor unresponsive to factor VIII inhibitor
      bypassing activity.
AB  - We report a patient with hemophilia A and high-titer factor VIII inhibitor who
      developed compartment syndrome of his forearm following trauma. Emergency
      fasciotomy was performed. Initial hemostatic treatment with factor VIII inhibitor
      bypassing activity (FEIBA) was unsuccessful. Bleeding was controlled with
      recombinant factor VIIa.

PMID- 15849768
TI  - Disseminated zygomycosis post allogeneic bone marrow transplantation.

PMID- 15849769
TI  - Alteration of p73 in acute myelogenous leukemia.
AB  - The frequency of p73 mutation is low in hematologic malignancies as well as solid
      tumors. In the present study, we scanned for mutations in the exons 4, 5, 6, and
      7 of p73, as well as methylation of the CpG island in the untranslated region of
      exon 1, in 100 de novo AML patients. Four patients showed mutation in exon 5 and
      one in exon 6, and none of the patients showed mutation in exons 4 and 7. None of
      the patients showed p73 gene methylation. The expression level of p73 mRNA was
      also examined in 40 AML samples using reverse transcriptase-polymerase chain
      reaction. Only six AML patients showed p73 mRNA expression, as analyzed by RT-PCR
      analysis. However, p73 over-expression in 30% of patients was demonstrated by
      immunocytochemistry and Western blot analysis. Further, mutation of p73 has been
      correlated with p73 mRNA and p73 protein status. The results show the presence of
      over-expressed p73 mRNA and protein in the samples with mutated p73 gene. Thus,
      it is presumed that mutation of p73 might lead to production of defective p73
      protein and p73 mRNA, and this might have a role in the process of leukemogenesis
      of AML. This report is the first demonstrating the presence of mutations in p73
      gene in acute myelogenous leukemia.

PMID- 15849770
TI  - Hospital readmission for adult acute sickle cell painful episodes: frequency,
      etiology, and prognostic significance.
AB  - The acute sickle cell painful episode is the most common cause of hospitalization
      of patients with sickle cell anemia. Its detailed clinical features and peri
      discharge features are not well known. In order to determine the actual pattern
      of hospital admissions of patients with SS and the causes of frequent hospital
      readmissions and their prognostic significance, we conducted a prospective
      longitudinal and observation cohort study of all adult patients with sickle cell
      anemia admitted to Thomas Jefferson University Hospital between January 1998 and
      December 2002. Major outcome measures included the frequency, etiology, and
      prognostic significance of readmissions to the hospital within 1 week and 1 month
      after discharge. Incidence of mortality among patients during the study period
      was also determined. Analysis of the data showed that about 50% of hospital
      admissions for acute painful episodes were readmitted within 1 month after
      discharge, and about 16% of all admissions were within 1 week after discharge.
      The intensity of pain score decreased significantly during the first 4 days of
      hospital admission (P < 0.001) and then reached a plateau until discharge. The
      mean score of pain intensity was >7 throughout the hospital stay. Causes of
      hospital readmission included premature discharge, withdrawal syndrome, and
      recurrence of new acute episodes. Readmission within 1 week after discharge was
      associated with higher mortality than otherwise. This study shows that hospital
      readmission of adult patients with sickle cell anemia is common. It suggests that
      improvement is needed in the management of pain during hospitalization and at
      home after discharge. Patients who are readmitted frequently within 1 week of
      discharge have poor prognosis and require careful monitoring.

PMID- 15849771
TI  - Slow infusion of platelets: a possible alternative in the management of
      refractory thrombocytopenic patients.

PMID- 15849772
TI  - Reversible drug-induced interstitial pneumonitis following imatinib mesylate
      therapy.

PMID- 15849773
TI  - RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia
      patient.
AB  - The t(1;22)(p13;q13) is a nonrandom chromosomal abnormality in acute leukemia
      with the fusion oncogene, RBM15-MKL1 (OTT-MAL), identified recently. However,
      this abnormality has been described only in infants and young children with acute
      megakaryoblastic leukemia (AMKL). We report a 59-year-old male patient with the
      diagnosis of acute myeloid leukemia, subtype M1, who harbors an abnormal
      chromosome +der(1)t(1;22)(p13;q13). The RBM15-MKL1 (OTT-MAL) fusion transcript
      was also confirmed by the reverse transcriptase-polymerase chain reaction. This
      unusual abnormality is rare in adult cases of leukemia, and in children it is
      restricted to AMKL. This report is accompanied by a review of the literature on
      the t(1;22)(p13;q13).

PMID- 15849774
TI  - Multicentric glial brain tumors of a varying degree of differentiation in patient
      with chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia is associated with an increased incidence of
      secondary neoplasms. Primary brain tumors are rarely seen; however, an increased
      risk relative to the general population has been observed in male patients with
      chronic lymphocytic leukemia. A case report of a 62-year-old man with progressive
      chronic lymphocytic leukemia and pronounced neurologic symptoms is presented.
      Richter's syndrome or brain infiltration with leukemia cells was clinically
      suspected and suggested by computed tomography findings. Progression of the
      neurologic symptoms rapidly continued and the patient died. Neuropathologic
      examination revealed multicentric glial tumors of a varying degree of
      differentiation located throughout the brain and cerebellum.

PMID- 15849775
TI  - HLA-DRB1 alleles in Hb SS patients with avascular necrosis of the femoral head.
AB  - Strong associations have been established between various HLA alleles and
      different complications of sickle cell disease (SCD). Recently, the HLA-DRB1*03
      allele was shown to be associated with susceptibility to stroke while the HLA
      DRB1*02 allele may be protective. While stroke and silent brain infarcts (SBI)
      are unusual in Kuwaiti children with SCD, avascular necrosis of the femoral head
      (AVNFH) is quite common. The modulatory association factors must still be
      elucidated. An investigation of HLA-DRB1 alleles was carried out in a group of 68
      Kuwaiti SS patients, of age 7-44 years, of whom 20 (29.4%) had AVNFH, confirmed
      by magnetic resonance imaging. A group of 167 apparently healthy age- and sex
      matched individuals served as controls. Comparison of the HLA alleles between the
      whole SS group and the controls showed a significant over-representation of
      DRB1*01 (P < 0.01) and DRB1*10 (P < 0.05) in the patient group. No significant
      differences in the allele frequencies in the SS patients with or without AVNFH
      were observed. It therefore appears that the HLA-DRB1 locus does not play a
      significant role in the pathogenesis of AVNFH Kuwaiti patients.

PMID- 15849776
TI  - High expression of urokinase plasminogen activator receptor (UPA-R) in acute
      myeloid leukemia (AML) is associated with worse prognosis.
AB  - Urokinase-type plasminogen activator receptor (UPA-R; CD87) is a membrane protein
      responsible for plasmin expression on cells facilitating cellular extravasations
      and tissue invasions. We studied the expression of the UPA-R on bone marrow (BM)
      cells of 93 patients with acute myeloid leukemia at first diagnosis and 8 healthy
      probands as controls by FACS analysis using phycoerythrin (PE)-conjugated
      antibodies. A case was defined as UPA-R-positive (UPA-R+) if >20% of the gated
      cells expressed UPA-R. Whereas none of the 8 healthy BM samples was positive for
      the UPA-R, 32 (34%) of the 93 AML samples were UPA-R+. Expression of UPA-R was
      heterogeneous in different FAB types, however, with the highest expression rates
      in monocytic subtypes (FAB M4/M5): 18%/19%/30% of UPA-R+ cases were found in
      M1/M2 or M3, and 58%/80% of cases with M4 or M5 were UPA-R+. Proportions of UPA
      R+ cells varied between 1% and 98% of the mononuclear cell fractions, with the
      highest proportions in M4/M5 subtypes (on average 27%/40% UPA-R+ cells) and the
      lowest expression in AML M2 (11% UPA-R+ cells). The density of expressed UPA-R,
      estimated as mean channel fluorescence activity, was highest in cases with AML M1
      (mFI: 124) followed by M4 and M5 (mFI: 78/77) and lowest in AML M2 (mFI: 43). In
      sAML, higher proportions of UPA-R+ cases (8 of 18; 44%) compared to pAML (24 of
      75; 32%) were found as well as higher proportions of UPA-R+ cells (27% vs. 19%).
      Separating our patients' cohort in cytogenetic risk groups, we could not detect
      significant differences in the UPA-R expression profiles. For evaluations of the
      clinical course of AML, only patients treated by the AML-CG protocol (n = 65)
      were included. In the group of patients who did not respond to AML-CG therapy,
      significantly higher proportions of UPA-R+ cells (31% vs. 14%, P = 0.0015, t
      test) were found. By evaluating a cut-off value for the percentage of positive
      cells that allows the most significant separation and differentiation between
      cases with shorter or longer relapse-free survival times, we could show that
      patients with >26.5% UPA-R-positive cells were characterized by a significantly
      higher risk for relapse compared to cases with <26.5% positive cells (P = 0.05).
      In summary, our data show a high expression of the UPA-R in AML, especially in
      (myelo)monocytoid subtypes. Cases with higher proportions of UPA-R+ cells were
      characterized by a significant lower remission rate after AML-CG therapy and a
      higher risk for relapse. Although prospective trials are still lacking, UPA-R is
      a prognostically relevant factor independent from the karyotype. UPA-R positivity
      may identify subtypes of AML associated with a more aggressive clinical course.
      Thus due to lower remission probabilities in UPA-R+ cases, a more intensive
      induction therapy regimen could be considered.

PMID- 15849777
TI  - The aspartimide problem in Fmoc-based SPPS. Part III.
AB  - A newly developed Fmoc-Asp derivative, Fmoc-Asp beta-(2,3,4-trimethyl-pent-3-yl)
      ester, has been tried in the Fmoc-based SPPS of H-Val-Lys-Asp-Xaa-Tyr-Ile-OH, a
      well-established peptide model for studying base-catalysed aspartimide formation.
      When synthesizing the hexapeptide incorporating Gly, Arg(Pbf), Asn(Mtt),
      Asp(OtBu) or Cys(Acm) for Xaa, considerable amounts of aspartimide-related by
      products were to be expected. The Asp(3) beta-carboxy protecting group and the
      duration of exposure to bases were varied. By-product formation could be reduced
      by incorporation of the new Asp derivative more efficiently than by introducing
      the less bulky Asp(OMpe). Significant improvements were observed in cases of
      prolonged contact with piperidine or DBU. Both beta-carboxy protecting groups
      were superior to the standard Asp(OtBu) which was also included in this study,
      but the additional stabilization gained by our new protecting group was valuable
      especially in syntheses of long peptides or difficult sequences.

PMID- 15849778
TI  - Antioxidative effect of a chymotrypsin inhibitor from Momordica cochinchinensis
      (Cucurbitaceae) seeds in a primary rat hepatocyte culture.
AB  - The antioxidative activity of a chymotrypsin-specific potato type I inhibitor
      from Momordica cochinchinensis (MCoCI) (Cucurbitaceae) has been investigated
      using the primary rat hepatocyte system. tert-Butyl hydroperoxide (t-BHP) was
      used to induce oxidative stress. Pretreatment of hepatocytes with MCoCI for 24 h
      significantly reversed t-BHP-induced cell damage, and the associated glutathione
      depletion and lipid peroxidation. The activities of glutathione-S-transferase and
      superoxide dismutase were also increased. These results suggested that MCoCI
      possessed antioxidative activity which may account for some of the
      pharmacological effects of Momordica cochinchinensis seeds, the traditional
      Chinese medicine known as Mubiezhi, from which MCoCI was isolated.

PMID- 15849779
TI  - Prenatal foetal diagnosis of partial trisomy 3q and monosomy 13p due to a
      maternal balanced rearrangement.
AB  - The authors describe a case of a male foetus whose ultrasound at 20 weeks'
      gestation revealed cystic hygroma, cleft lip and ventricular septal defect.
      Amniotic fluid cytogenetics using GTG banding showed a
      46,XY,der(13)t(3;13)(q12;p11.1) rearrangement, and fluorescence in situ
      hybridization (FISH) delineated the relevant breakpoints. Familial studies
      identified a maternal balanced translocation involving chromosomes 3 and 13. The
      post-mortem examination confirmed the prenatal ultrasound findings.

PMID- 15849780
TI  - Isolation and sequence analysis of the gene URA3 encoding the orotidine-5'
      phosphate decarboxylase from Candida glycerinogenes WL2002-5, an industrial
      glycerol producer.
AB  - The URA3 gene of Candida glycerinogenes WL2002-5, an industrial glycerol producer
      encoding orotidine-5'-phosphate decarboxylase enzyme, was isolated by
      complementation cloning in Saccharomyces cerevisiae. DNA sequence analysis
      revealed the presence of an open reading frame (ORF) of 786 bp, encoding a 262
      amino acid protein, which shares 71.65% amino acid sequence similarity to the S.
      cerevisiae URA3 protein. Furthermore, the cloned ORF fully complemented the ura3
      mutation of S. cerevisiae, confirming that it encodes for the C. glycerinogenes
      Ura3 (CgUra3) protein.

PMID- 15849781
TI  - Evaluation of the Saccharomyces cerevisiae ADH2 promoter for protein synthesis.
AB  - The Saccharomyces cerevisiae ADH2 promoter (P(ADH2)) is repressed several hundred
      fold in the presence of glucose; transcription is initiated once the glucose in
      the medium is exhausted. The promoter can thus be utilized for effective
      regulation of recombinant gene expression in S. cerevisiae without the addition
      of an inducer. To evaluate this promoter in the absence of plasmid copy number
      and stability variations, the P(ADH2)-lacZ cassette was integrated into the yeast
      chromosomes. The effects of medium composition, glucose concentration and
      cultivation time on promoter derepression and expression level were investigated.
      Maximum protein activity was obtained after 48 h of growth in complex YPD medium
      containing 1% glucose. The widely used S. cerevisiae GAL1 and CUP1 promoters both
      require the addition of an inducer [galactose and copper(II) ion, respectively]
      before regulated genes will be expressed. The strengths of these three different
      promoters were compared for cells containing one copy of an integrated lacZ gene
      under their control. The ADH2 promoter was superior for all induction strategies
      investigated.

PMID- 15849782
TI  - Reproductive history of a healthy woman with mosaic duplication of chromosome 4p.
AB  - OBJECTIVES: Mosaic autosomal duplications are rare and often result in mental
      retardation and congenital anomalies. Phenotype is not predictable depending on
      the chromosomal imbalance involved and the percentage and tissues distribution of
      unbalanced cells. We report on a young woman carrying a mosaic duplication of
      chromosome 4p, evaluated because of three abortions due to IUGR and fetal
      malformation. METHODS: Mosaic dup(4p) was detected by standard and molecular
      cytogenetics. RESULTS: Unbalanced cells accounted for about 20 to 30% of nuclei
      in four examined tissues and did not cause any obvious phenotypic effect.
      CONCLUSION: It is likely that mosaic duplications are underascertained because
      they are not associated with obvious clinical effects in some individuals.
      Prenatal diagnosis is the method of choice to predict the karyotype in the
      offspring of subjects carrying mosaic chromosome imbalances.

PMID- 15849783
TI  - Population-based study of the outcome following the prenatal diagnosis of cystic
      hygroma.
AB  - OBJECTIVE: To identify the population prevalence, pregnancy outcome, and the
      pattern of associated anomalies with a prenatal diagnosis of cystic hygroma.
      DESIGN: We analysed the pregnancy outcomes from 99 cases of prenatally diagnosed
      cystic hygroma reported to the Trent Congenital Anomalies Register from 1 January
      1997 to 31 December 1999, by means of an outcome reporting form completed by the
      notifying centre. RESULTS: We identified a population prevalence of 1 in 1775
      livebirths for prenatally diagnosed cystic hygroma. There were 64 terminations of
      pregnancy, 19 spontaneous pregnancy failures, and 16 livebirths. Of the 87
      pregnancies karyotyped, 53 (61%) demonstrated aneuploidy with Turner syndrome
      being the most common, 29 (33%). There were a large variety of structural
      malformations identified, however, only 14 out of 83 terminations of pregnancy
      and spontaneous pregnancy failures had post-mortem examinations. Termination of
      pregnancy for Turner syndrome not complicated by identified structural
      malformations was the norm. Of the 16 livebirths, only 6 were normal at birth, 1
      other has had successful hygroma surgery. Four of the liveborn infants have since
      died. CONCLUSIONS: The 'normal outcome' rate from pregnancies complicated by
      prenatally diagnosed cystic hygroma is less than 10% in this study (6/99).
      Prenatal diagnosis of cystic hygroma requires careful assessment of the fetus,
      with regard to both karyotyping and ultrasound. Post-mortem examination should be
      encouraged after termination of pregnancy, or spontaneous pregnancy loss. This is
      important not just to the current pregnancy but also for future pregnancies.

PMID- 15849784
TI  - Sonographic genital ambiguity in a fetus due to a mosaic 45,X/46,X,idic(Y)(qter
      p11.32::p11.32-qter) karyotype.
AB  - Nowadays, improved ultrasound techniques enable the detection of more subtle
      congenital abnormalities at an earlier stage of fetal development. Current
      cytogenetic techniques can characterize a chromosomal abnormality in greater
      detail. These advancements in both diagnostic possibilities have helped to answer
      many questions but have also created new issues and dilemmas in counselling. This
      is illustrated by this case report of a 35-year-old woman, who presented at the
      end of the second trimester of her first pregnancy. Sonographic examination
      indicated an abnormal external genital in a male fetus. A differential diagnosis
      of hypospadia was made. During follow-up, an amniocentesis was performed, and
      this showed a 45,X/46,X,idic(Y)(qter-p11.32::p11.32-qter) karyotype as the cause
      of the sonographic findings. Cytogenetic characterization of the isodicentric Y
      chromosome and pre- and post-natal findings in the child are reported. Cases with
      a similar karyotype reported in the literature are reviewed.

PMID- 15849785
TI  - Cloning and heterologous expression of the NADPH cytochrome P450 oxidoreductase
      genes from an industrial dicarboxylic acid-producing Candida tropicalis.
AB  - NADPH cytochrome P450 oxidoreductase (CPR) catalyses the transfer of electrons
      during P450-mediated oxidation, which plays an important role in the omega
      oxidation pathway of Candida tropicalis. Two putative allelic genes, CPR-a and
      CPR-b, were cloned from the long chain dicarboxylic acid-producing Candida
      tropicalis 1230, using cassette PCR methods. Both the identified open reading
      frames predict the gene products of 679 amino acid residues. The deduced amino
      acid sequences of CPR-a and CPR-b are highly homologous to CPR genes from C.
      tropicalis ATCC 750 and Candida maltosa. Both genes were individually expressed
      in a cpr mutant of Saccharomyces cerevisiae with high CPR activities, in which
      only a small distinction was observed between recombinant CPR-a and CPR-b. Both
      CPR-a and CPR-b contain one CTG codon, which codes for serine (amino acid 50) in
      C. tropicalis rather than universal leucine. A mutated cDNA of CPR-a with a TCG
      codon instead of CTG codon was constructed and expressed, resulting in little
      increase in CPR activity. This indicates that the alteration of Ser-50 has little
      effect on functional expression of CPR. Furthermore, high ketoconazole
      sensitivity for the cpr mutant was complemented by heterologous expression of the
      cloned CPR-a or CPR-b.

PMID- 15849786
TI  - Successful in utero treatment of parvovirus B19-induced fetal hydrops in a case
      of twin pregnancy.

PMID- 15849787
TI  - TOR kinase pathway and 14-3-3 proteins regulate glucose-induced expression of
      HXT1, a yeast low-affinity glucose transporter.
AB  - Expression of HXT1, a gene encoding a Saccharomyces cerevisiae low-affinity
      glucose transporter, is regulated by glucose availability, being activated in the
      presence of glucose and inhibited when the levels of the sugar are scarce. In
      this study we show that 14-3-3 proteins are involved in the regulation of the
      expression of HXT1 by glucose. We also demonstrate that 14-3-3 proteins, in
      complex with Reg1, a regulatory subunit of Glc7 protein phosphatase, interact
      physically with Grr1 (a component of the SCF-Grr1 ubiquitination complex), a key
      player in the process of HXT1 induction by glucose. In addition, we show that the
      TOR kinase pathway participates actively in the induction of HXT1 expression by
      glucose. Inhibition of the TOR kinase pathway by rapamycin treatment abolishes
      HXT1 glucose induction. A possible involvement of PP2A protein phosphatase
      complex, through the Cdc55 B-subunit, in the glucose induction of HXT1 is also
      discussed.

PMID- 15849788
TI  - Prenatal diagnosis of de novo partial trisomy 13q (13q22 --> qter) and partial
      monosomy 8p (8p23.3 --> pter) associated with holoprosencephaly, premaxillary
      agenesis, hexadactyly, and a hypoplastic left heart.

PMID- 15849789
TI  - Risk of a Down syndrome live birth in women 45 years of age and older.
AB  - OBJECTIVES: To determine the risk of a Down syndrome (DS) live birth for women 45
      years of age and over. METHODS: A meta-analysis of data from five published
      articles, 13 EUROCAT congenital anomaly population registers and two unpublished
      sources. RESULTS: Information was available on the number of DS live births
      occurring amongst 13,745 live births to women 45 years of age and over.
      Information was also available on DS pregnancies diagnosed prenatally that were
      subsequently terminated. These pregnancies were adjusted for expected fetal loss
      to estimate the number of live births that would have occurred in the absence of
      prenatal diagnoses, when a total of 471 DS live births were estimated to have
      occurred. The risk of a DS birth did not increase for women 45 years of age and
      over. The average risk was 34 per 1000 births (95% CI: 31-37). CONCLUSION: The
      risk of a DS live birth for women 45 years of age and over is considerably lower
      than has often been previously assumed. The most likely explanation is that women
      of this age are more likely to miscarry DS pregnancies than younger mothers.

PMID- 15849790
TI  - The natural history of fetal growth restriction in women with abnormal uterine
      artery Doppler.

PMID- 15849791
TI  - First-trimester diagnosis of thrombocytopenia-absent radius (TAR) syndrome in a
      triplet pregnancy.

PMID- 15849792
TI  - Developmental outcome of children who had choroid plexus cysts detected
      prenatally.
AB  - OBJECTIVE: The purpose of this study was to evaluate cognitive, motor, language
      and adaptive behavior development in children who had isolated choroid plexus
      cysts (CPC) detected prenatally. METHODS: A retrospective double cohort design
      and standardized psychometric measures were used to compare the development of
      children who had isolated CPCs identified prenatally with a control group of
      children who had normal prenatal ultrasounds. RESULTS: Our study cohort (n = 37)
      had a mean age of 3.88 years (SD = 0.83) and the control cohort (n = 48) had a
      mean age of 4.62 years (SD = 1.03). The age difference between our cohorts was
      significant. There were no differences between cohorts in socioeconomic status,
      sex, birth weight or gestational age. Cognitive data showed no clinically
      significant difference in Full Scale IQ using the WISC-III or WPPSI-R (CPC =
      113.97, control = 116.69). Scores on standardized measures of motor and adaptive
      functioning also did not show any significant group differences. Children with
      CPCs did score significantly lower than controls on some of the measures of
      verbal functioning; however, this difference was not associated with clinically
      significant delays. CONCLUSION: We conclude that the presence of isolated CPCs on
      midtrimester ultrasound are unlikely to be associated with any significant
      neurocognitive delays in early childhood.

PMID- 15849793
TI  - A comparison of maternal age, sex ratio and associated major anomalies among
      fetal trisomy 18 cases with different cell division of error.
AB  - OBJECTIVES: To compare the maternal age, sex ratio, and associated major
      anomalies among fetal trisomy 18 cases with different cell division of error.
      METHODS: Thirty-one consecutive cases of fetal trisomy 18 detected perinatally
      during a period of 6 years were studied. Among these, 18 were 47,XY,+18, and 13
      were 47,XX,+18. The average gestational age at diagnosis was 19.7 +/- 4.6 weeks,
      and the maternal age at diagnosis was 34.5 +/- 5.8 years. DNA polymorphism
      analysis was applied to determine the parental origin, stage of non-disjunctional
      error and recombination. RESULTS: Twenty-eight cases were of maternal origin.
      Among these, 20 had major anomalies, 17 had meiosis II (MII) errors, 10 had
      meiosis I (MI) errors, and one had a postzygotic mitotic (PZM) or non-crossover
      MII error. Three cases were of paternal origin. Among these, two had major
      anomalies, two had MI errors, and one had a PZM or non-crossover MII error. For
      the 17 cases with maternal MII errors, the average maternal age was 34.5 +/- 6.6
      years. Of these cases, 12 had major anomalies, 13 were male, and 4 were female,
      giving a male:female sex ratio of 3.25:1. For the 10 cases with maternal MI
      errors, the average maternal age was 34.8 +/- 5.7 years. Of these cases, seven
      had major anomalies, three were male, and seven were female, giving a male:female
      sex ratio of 0.429:1. CONCLUSION: In trisomy 18, there is a male preponderance in
      the fetuses caused by maternal MII errors and a female preponderance in the
      fetuses caused by maternal MI errors. No significant difference was noted in
      maternal age or in associated major anomalies between the two groups of maternal
      MII errors and maternal MI errors. No significant difference was noted in
      associated major anomalies between the maternal and paternal cases.

PMID- 15849794
TI  - Molecular cloning and biochemical characterization of a 3'(2'),5'-bisphosphate
      nucleotidase from Debaryomyces hansenii.
AB  - The enzyme 3'(2'),5'-bisphosphate nucleotidase catalyses a reaction that converts
      3'-phosphoadenosine-5'-phosphate (PAP) to adenosine-5'-phosphate (AMP) and
      inorganic phosphate (Pi). The enzyme from Saccharomyces cerevisiae is highly
      sensitive to sodium and lithium and is thus considered to be the in vivo target
      of salt toxicity in yeast. In S. cerevisiae, the HAL2 gene encodes this enzyme.
      We have cloned a homologous gene, DHAL2, from the halotolerant yeast Debaryomyces
      hansenii. DNA sequencing of this clone revealed a 1260 bp open reading frame
      (ORF) that putatively encoded a protein of 420 amino acid residues. S. cerevisiae
      transformed with DHAL2 gene displayed higher halotolerance. Biochemical studies
      showed that recombinant Dhal2p could efficiently utilize PAP (K(m)17 microM) and
      PAPS (K(m)48 microM) as substrate. Moreover, we present evidence that, in
      comparison to other homologues from yeast, Dhal2p displays significantly higher
      resistance towards lithium and sodium ions.

PMID- 15849795
TI  - Two new fungal inteins.
AB  - Until recently the only intein known to be encoded by the nuclear genome of a
      eukaryote was the VMA intein in the vacuolar ATPase precursor of several species
      of saccharomycete yeast. This intein has been intensively studied and much
      information has been gained about its structure, mode of action and evolutionary
      history. We recently reported a second nuclear intein, Cne PRP8, encoded within
      the PRP8 gene of the basidiomycete Cryptococcus neoformans. Subsequent studies
      have found allelic PRP8 inteins in several species of yeast and filamentous
      ascomycetes. Here we report two further, non-allelic, inteins from ascomycete
      species. The yeast Debaryomyces hansenii (which also has a VMA intein) has an
      intein encoded within the sequence of the glutamate synthase gene (GLT1). There
      are also inteins encoded in the homologous GLT1 genes of the yeast Candida
      (Pichia) guilliermondii and the filamentous fungus Podospora anserina. These
      allelic GLT1 inteins occupy exactly the same site in the glutamate synthase and
      all contain domains that indicate the presence of a homing endonuclease (HEG).
      Podospora anserina, in addition, contains a second, non-allelic, intein encoded
      in the chitin synthase gene (CHS2); this intein also contains a HEG domain. We
      describe the phylogenetic relationships among the four eukaryote nuclear encoded
      inteins (VMA, PRP8, GLT1 and CHS2). We also consider this phylogeny in the
      broader context of eubacterial, archaeal and eukaryote viral and organelle
      inteins.

PMID- 15849796
TI  - A fragile site at 10q23 (FRA10A) in a phenytoin-exposed fetus: a case report and
      review of the literature.
AB  - OBJECTIVE: To report fragility at 10q23.3 in a fetus exposed to phenytoin during
      pregnancy. Review of the literature. METHODS: Amniocytes were cultured in A10
      (WISENT) culture medium. Molecular polymorphism studies of MTHFR gene using PCR
      were performed on fetal tissues. RESULTS: The fragile site was expressed in all
      22 amniocyte colonies analyzed. Analysis of fetal blood showed
      46,XX[98]/46,XX,fra(10)(q23.3)[3]/46,XX,del(10)(q23.3) [1]. Molecular studies of
      the MTHFR (methylenetetrahydrofolate reductase) gene identified a compound
      heterozygote genotype for two polymorphisms, 677C>T and 1298A>C. CONCLUSION: The
      fragility at 10q23.3 is unlikely to be due to culture condition-induced folic
      acid deficiency (medium contains folate). It is possible that this finding
      represents a previously undescribed folic acid-insensitive fragile site in the
      region of 10q23.3. Alternatively, the fetal cells may have had decreased folate
      metabolism, and the fragile site was the known folate-sensitive FRA10A. Since
      phenytoin has been shown to decrease MTHFR activity in mice, we postulate that
      the fragile site at 10q23.3 in this fetus may have arisen secondary to a
      combination of the polymorphisms in MTHFR and exposure to this drug, and is
      indeed FRA10A.

PMID- 15849797
TI  - Impact of ionizing radiation on the life cycle of Saccharomyces cerevisiae Ty1
      retrotransposon.
AB  - Ty1 elements, LTR-retrotransposons of Saccharomyces cerevisiae, are known to be
      activated by genetic and environmental stress. Several DNA-damaging agents have
      been shown to increase both Ty1 transcription and retrotransposition. To explore
      further the relationship between Ty1 mobility and DNA damage, we have studied the
      impact of ionizing radiation at different steps of the Ty1 life cycle. We have
      shown that Ty1 transposition is strongly activated by gamma-irradiation and we
      have analysed its effect on Ty1 transcription, TyA1 protein and Ty1 cDNA levels.
      The activation of transposition rises with increasing doses of gamma-rays and is
      stronger for Ty1 elements than for the related Ty2 elements. Ty1 RNA levels are
      markedly elevated upon irradiation; however, no significant increase of TyA1
      protein was detected as measured by TYA1-lacZ fusions and by Western blot. A
      moderate increase in Ty1 cDNA levels was also observed, indicating that ionizing
      radiation can induce the synthesis of Ty1 cDNA. In diploid cells and ste12
      mutants, where both Ty1 transcription and transposition are repressed, gamma
      irradiation is able to activate Ty1 transposition and increases Ty1 RNA levels.
      These results suggest the existence of a specific regulatory pathway involved in
      Ty1 response to the gamma-irradiation that would be independent of Ste12 and
      mating-type factors. Our findings also indicate that ionizing radiation acts on
      several steps of the Ty1 life cycle.

PMID- 15849798
TI  - Dandy-Walker syndrome and corpus callosum agenesis in 5p deletion.
AB  - 5p deletion syndrome commonly known as cri du chat is well described in affected
      neonates with catlike cry and hypotonia. Karyotyping will usually show a deletion
      of the short arm of one chromosome 5 with variable breakpoints. Only a few cases
      have been reported prenatally, and the fetal form of the syndrome has not been
      clearly individualised. We report a new case of 5p deletion syndrome diagnosed
      prenatally in association with Dandy-Walker syndrome and agenesis of the corpus
      callosum. Other brain anomalies have been reported previously, but this unusual
      association suggests the use of a specific probe in the investigation of these
      malformations.

PMID- 15849799
TI  - Fluorescent in situ hybridization (FISH) on paraffin-embedded placental tissues
      as an adjunct for understanding the etiology of early spontaneous abortion.
AB  - OBJECTIVES: An investigation of first-trimester spontaneous abortions (SAs) for
      those cases in which karyotype is not available was designed to test the
      efficiency of fluorescence in situ hybridization (FISH) on paraffin-embedded
      tissues combined with pathological examination for understanding the etiology of
      SAs. METHODS: Pathological examination of 202 placental tissues from SAs was
      performed. FISH analysis was then carried out on paraffin-embedded tissue
      sections from the same abortion products with probes specific for chromosomes 13,
      16, 18, 21, X, Y. RESULTS: FISH could be achieved in 196 cases (97%). After
      pathological analysis alone, the etiology of SAs was evoked in 40 cases. The
      suspected diagnosis was confirmed by FISH in 26 cases (13.2%). After combined
      pathological and FISH analysis, the etiology of SAs was identified in 83 from the
      196 cases (42.3%) with the probe set used. CONCLUSION: The present study
      demonstrates the value of FISH on paraffin-embedded tissues as an adjunct for
      understanding the etiology of SAs for those cases in which karyotype is not
      available. Combination of pathological and FISH analysis increases the yield of
      diagnosis by a factor of 3.2. The results also demonstrate that predictions of
      the karyotype from pathological examination should be avoided.

PMID- 15849800
TI  - The association of umbilical cord hemangioma with fetal vascular birthmarks.
AB  - OBJECTIVE: To report a rare case of umbilical cord hemangioma and to discuss its
      association with vascular birthmarks. METHODS: A case of umbilical cord
      hemangioma diagnosed by ultrasound at 28 weeks of gestation is reported. After
      labor induction at 38 weeks of gestation, a male infant was born. Examination of
      the newborn showed disseminated port wine flat skin lesions covering a
      significant part of his body. Reviewing the scientific literature revealed the
      association between umbilical cord hemangioma and fetal mortality and morbidity,
      in particular, vascular malformations. RESULTS: A total of 24 umbilical cord
      hemangioma cases were reported in detail. Of them, 37.5% were associated with
      perinatal mortality and 29.2% ended in the delivery of a normal healthy infant.
      Fetal morbidity was recognized in 33.3%. CONCLUSION: This case illustrates the
      importance of prenatal diagnosis of umbilical cord hemangioma for prenatal
      counseling.

PMID- 15849801
TI  - Y chromosome heterochromatin of differing lengths in two cell populations of the
      same individual.
AB  - OBJECTIVE: To present a prenatal diagnosis report on a case where G-banding
      analysis of fetal metaphase chromosomes showed populations of cells with two
      different Y chromosomes; one with a short block of heterochromatin (Yqh-) and one
      with a longer block of heterochromatin (Yqh+). METHODS: These two populations of
      the Y chromosome were studied using fluorescent quinacrine banding and
      fluorescent in situ hybridization (FISH). A chromosome paint corresponding to the
      euchromatic region of the Y chromosome, and probes corresponding to the SRY,
      DYZ1, and DYZ3 regions were used for this study. RESULTS: Both Y chromosomes
      appeared to be structurally normal by these analyses. Subsequent ultrasound
      examination at 20 weeks' gestation revealed normal male genitalia. Follow-up with
      a neonatal blood sample analysis confirmed the above findings. CONCLUSIONS: This
      study reports a direct prenatal diagnosis case of two populations of the Y
      chromosome in the same individual. This apparent mosaicism may be explained by a
      postzygotic simple deletion or unequal crossover event between sister chromatids
      in the DYZ region.

PMID- 15849802
TI  - Two contact-point chiral distinction: model CHFClBr dimers.
AB  - Dimers of the simple chiral molecule CHFClBr have been studied using a variety of
      computational approaches, including HF, MP2, and DFT B3LYP and the 6-31G*, 6
      31++G**, and 6-311++G** basis sets. Both heterochiral and homochiral dimers were
      studied to allow analysis of the chiral distinction in these systems. The dimers
      were arranged in edge-to-edge orientations with assorted combinations of two
      contact-points ("2:2e") between the dimers. The monomers were constrained to
      tetrahedral symmetry. We demonstrate that chiral distinction does indeed occur in
      these two contact-point models. While the stabilization energies are driven by
      the interactions of the nearest atoms (contacts) in the complexes, the degree of
      chiral distinction is driven by the profile of changing atoms, which, in the
      present systems, are often the distal atoms of the complexes. Moreover, the
      chiral distinction does not correlate with the stabilization energies. The terms
      contact-points and interactions are defined.

PMID- 15849803
TI  - Lobar holoprosencephaly: prenatal MR diagnosis with postnatal MR correlation.
AB  - Holoprosencephaly is a congenital anomaly characterized by lack of cleavage of
      the prosencephalon. Although, relatively rare, it is the most common anomaly that
      involves both the brain and the face. Prenatal diagnosis of this anomaly using
      ultrasonography, particularly of the less severe forms, is difficult. Magnetic
      resonance imaging has recently become an important complement to US in prenatal
      diagnosis of CNS anomalies. We herein report a patient in whom, at 23 weeks of
      gestation, US suggested agenesis of the corpus callosum and in whom, at 24 weeks
      of gestation, MRI correctly diagnosed lobar holoprosencephaly, which was
      confirmed by a postnatal MRI at 3 weeks of age.

PMID- 15849804
TI  - Two-dimensional vs. two- plus four-dimensional ultrasound in pregnancy and the
      effect on maternal emotional status: a randomized study.
AB  - OBJECTIVE: To assess whether the addition of four-dimensional (4D) ultrasound to
      a conventional two-dimensional (2D) scan in the second/third trimester of
      pregnancy facilitates maternal recognition of specific fetal structures and
      movements and causes an emotional impact, as subjectively perceived by the woman.
      METHODS: Fifty-two women were randomly assigned to 2D ultrasound only (Group 1),
      while 48 women underwent 2D plus 4D ultrasound (Group 2). All the women completed
      two questionnaires. One questionnaire listed the fetal structures and movements
      that the women had recognized during the 2D scan or, for those women who also
      underwent a 4D scan, during the combination of the two; the other questionnaire
      required the women to score on an analog scale whether they had seen all the
      fetal parts and movements that they wished to see, whether they were satisfied
      with the scan, and if the scan had changed for the better their perception of the
      fetus. A subgroup of 46 women completed the Maternal Antenatal Attachment Scale
      (MAAS) designed to measure antenatal emotional attachment. RESULTS: Similar
      percentages of women in the two groups visualized fetal structures and movements,
      but facial expressions and hand-to-mouth movements were twice as likely to be
      seen with 4D ultrasound, although this difference did not reach statistical
      significance. The percentage of women who reported that they had seen all the
      fetal parts and movements that they wished to see, and of those who were
      satisfied overall with the scan, were similar in the two groups. There was no
      difference in the percentage of women who felt that the scan had changed for the
      better their perception of the fetus. Although the MAAS scores were similar in
      the two groups, there were more women with positive quality, intensity and global
      attachment among those who had undergone a 4D scan. Women who had seen all the
      fetal parts and movements they wished to see (whether with 2D or 2D plus 4D)
      answered more frequently that the scan had changed for the better their
      perception of the fetus. CONCLUSION: This randomized study indicates that the
      addition of 4D ultrasound does not change significantly the perception that women
      have of their baby nor their antenatal emotional attachment compared with
      conventional 2D ultrasound.

PMID- 15849805
TI  - Studies toward the synthesis of azadirachtin, part 2: construction of fully
      functionalized ABCD ring frameworks and unusual intramolecular reactions induced
      by close-proximity effects.

PMID- 15849806
TI  - Phase I/II enzyme gene polymorphisms and esophageal cancer risk: a meta-analysis
      of the literature.
AB  - AIM: Phase I/II enzymes metabolize environmental carcin-ogens and several
      functional polymorphisms have been reported in their encoding genes. Although
      their significance with regard to esophageal carcinogenicity has been examined
      epidemiologically, it remains controversial. The present systematic review of the
      literature was performed to clarify associations. METHODS: Eligible studies were
      case-control or cohort studies published until September 2004 that were written
      in any language. From PubMed and a manual review of reference lists in relevant
      review articles, we obtained 16 studies related to the CYP1A1 Ile-Val
      substitution in exon 7, CYP1A1 MspI polymorphisms, CYP2E1 RsaI polymorphisms,
      GSTM1 null type, GSTT1 null type and GSTP1 Ile104Val. All were of case-control
      design. Summary statistics were odds ratios (ORs) comparing heterozygous-,
      homozygous-non-wild type or these two in combination with the homozygous wild
      type, or the null type with the non-null type for GSTM1 and GSTT1. A random
      effect model was used to estimate the summary ORs. A meta-regression analysis was
      applied to explore sources of heterogeneity. RESULTS: Individuals with the Ile
      Val substitution in CYP1A1 exon 7 had increased esophageal cancer risk, with ORs
      (95%CI) compared with Ile/Ile of 1.37 (1.09-1.71), 2.52 (1.62-3.91) and 1.44
      (1.17-1.78) for Ile-Val, Val/Val genotype and the combined group. No significant
      association was found between esophageal cancer risk and the other genetic
      parameters. CONCLUSION: A significant association exists between the CYP1A1 Ile
      Val polymorphism and risk of esophageal cancer. Polymorphisms that increase the
      internal exposure to activated carcinogens may increase the risk of esophageal
      cancer.

PMID- 15849807
TI  - Inducible nitric oxide synthase, nitrotyrosine and apoptosis in gastric
      adenocarcinomas and their correlation with a poor survival.
AB  - AIM: To detect the presence of inducible nitric oxide synthase (iNOS),
      nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible
      correlations with the clinicopathological characteristics and prognosis of
      gastric adenocarcinoma. METHODS: Sixty-six specimens of gastric adenocarcinoma
      and corresponding adjacent normal gastric tissues were studied.
      Immunohistochemistry was employed to localize iNOS and NT protein and an
      immunohistochemical scoring system was used. The occurrence of apoptotic cell
      death (apoptotic index (AI)) was analyzed by the terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL)
      method. RESULTS: Results showed that iNOS expression was detected at an
      intermediate or high level in 41 of 66 (62%) specimens of gastric adenocarcinoma.
      NT expression was 58%. Neither of them was found in the normal gastric tissues;
      there were significant positive correlations among iNOS expression, NT expression
      and AI. Many clinicopathologic characteristics of gastric adenocarcinoma, such as
      tumor size, depth of invasion, lymph node metastasis and TNM staging, were
      related to iNOS and NT expressions (P<0.05). In 66 surviving patients, the 5-year
      survival rate of 41 patients who had tumors with intermediate or high iNOS
      expressions and high AIs (4.09%; 19.96%) was significantly lower than that of 25
      patients who had tumors with negative or low iNOS expressions and low AIs (0.79%;
      47.14%) (P = 0.001). COX's multivariate analysis revealed that the iNOS
      expression was identified as one of the significant independent prognostic
      factors predictive of a poor survival (relative risk (RR) = 2.69). CONCLUSION: NO
      produced by iNOS may play a stronger role in promoting gastric adenocarcinoma
      growth than in suppressing its growth. iNOS and NT expressions by gastric
      adenocarcinoma may correlate with a poor survival.

PMID- 15849808
TI  - Dynamic expression of pepsinogen C in gastric cancer, precancerous lesions and
      Helicobacter pylori associated gastric diseases.
AB  - AIM: To investigate the relationship between the expression of pepsinogen C (PGC)
      and gastric cancer, precancerous diseases, and Helicobacter pylori (H pylori)
      infection. METHODS: The expression of PGC was determined by immunohistochemistry
      method in 430 cases of gastric mucosa. H pylori infection was determined by HE
      staining, PCR and ELISA in 318 specimens. RESULTS: The positive rate of PGC
      expression in 54 cases of normal gastric mucosa was 100%. The positive rates of
      PGC expression in superficial gastritis or gastric ulcer or erosion, atrophic
      gastritis or gastric dysplasia and gastric cancer decreased significantly in
      sequence (P<0.05; 100%/89.2% vs 14.3%/15.2% vs 2.4%). The over-expression rate of
      PGC in group of superficial gastritis with H pylori infection was higher than
      that in group without H pylori infection (P<0.05; chi2= 0.032 28/33 vs 15/25).
      The positive rate of PGC expression in group of atrophic gastritis with H pylori
      infection was lower than that in group without H pylori infection (P<0.01; chi2=
      0.003 4/61 vs 9/30), and in dysplasia and gastric cancer. CONCLUSION: The level
      of PGC expression has a close relationship with the degree of malignancy of
      gastric mucosa and development of gastric lesions. There is a relationship
      between H pylori infection and expression of antigen PGC in gastric mucosa, the
      positive rate of PGC expression increases in early stage of gastric lesions with
      H pylori infection such as gastric inflammation and decreases during the late
      stage such as precancerous diseases and gastric cancer. PGC-negative cases with H
      pylori-positive gastric lesions should be given special attention.

PMID- 15849809
TI  - Long-term effects of proglumide on resection of cardiac adenocarcinoma.
AB  - AIM: Patients with advanced stage cardiac adenocarcinoma have a very poor
      prognosis. Surgery is the first choice of treatment for this kind of patients.
      Peptide hormone gastrin is a recognized growth factor for gastric cancer, and
      gastrin receptor antagonist proglumide can block the effects of gastrin. The aim
      of this study was to investigate the actions of proglumide as an adjuvant
      treatment to improve the postoperative long-term survival rate of patients with
      cardiac adenocarcinoma. METHODS: We performed a randomized, controlled study of
      gastrin receptor antagonist proglumide in 301 patients with cardiac
      adenocarcinoma after proximal subtotal gastrectomy. The oral dose of 0.4 g
      proglumide thrice daily preprandially was maintained for more than 5 years in 153
      cases (proglumide treatment group). In the control group, 148 patients underwent
      operation only. In clinicopathologic features, there was no significant
      difference between the two groups (P>0.05). All patients were followed up during
      their lifetime, and the survival rates were analyzed combined with
      clinicopathologic factors by SPSS 11.5 statistical software. RESULTS: The 1, 3, 5
      and 10-year survival rate of the patients was 88.4%, 48.8%, 22.6% and 13.4%,
      respectively. The 1, 3, 5 and 10-year survival rate of the proglumide treatment
      group was 90.2%, 49.7%, 26.8% and 17.6% compared to 86.5%, 48.0%, 18.2% and 8.9%
      of the control group. There was a significant difference between the two groups
      (P = 0.0460). The patients in proglumide treatment group had no obvious side
      effects after administration of the drug, and no definite hepatic and renal
      function damage was found. According to single factor log-rank analysis, the long
      term survival rate was correlated with the primary tumor position (P = 0.0205),
      length of the tumor (P = 0.0000), property of the operation (P = 0.0000),
      histopathologic grading (P = 0.0003), infiltrating degree of the tumor (P =
      0.0000), influence of lymph node metastasis (P = 0.0000), clinicopathologic
      staging (P = 0.0000) and administration of proglumide (P = 0.0460). Cox
      regression analysis demonstrated the infiltrating degree of tumor (P = 0.000),
      influence of lymph node metastasis (P = 0.039) and the clinicopathologic staging
      (P = 0.003) were independent prognostic factors. Administration of proglumide (P
      = 0.081), length of the tumor (P = 0.304), radical status of the resection (P =
      0.224) and histopathologic types (P = 0.072) were not the independent prognostic
      factors. CONCLUSION: Proglumide is convenient to use with no obvious toxic side
      effects, and prolonged postoperative administration of proglumide as a
      postoperative adjuvant treatment can increase the survival rate of patients after
      resection of cardiac adenocarcinoma. Proglumide may provide a new effective
      approach of endocrinotherapy for patients with gastric cardiac cancer.

PMID- 15849810
TI  - Fiber-modified adenoviral vector expressing the tumor necrosis factor-related
      apoptosis-inducing ligand gene from the human telomerase reverse transcriptase
      promoter induces apoptosis in human hepatocellular carcinoma cells.
AB  - AIM: Because of a major resistance to chemotherapy, prognosis of hepatocellular
      carcinoma (HCC) is still poor. New treatments are required and gene therapy may
      be an option. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      induces apoptosis in multiple malignant tumors, and using adenoviral vectors has
      shown a targeted tumor-specific therapy. However, repeated administration of
      adenoviral vectors can lead to cell resistance, which may be caused by the
      initial coxsackie-adenovirus receptor (CAR). One technique to overcome resistance
      is the use of modified adenoviral vectors containing an Arg-Gly-Asp (RGD)
      sequence. In this study we constructed an adenoviral vector (designated Ad/TRAIL
      F/RGD) with RGD-modified fibers, expressing the TRAIL gene from the human
      telomerase reverse transcriptase (hTERT) promoter, and evaluated its antitumor
      activity in HCC cell lines. METHODS: To investigate the effects of Ad/TRAIL-F/RGD
      in human HCC cell lines Hep G2 and Hep 3b, cells were infected with Ad/CMV-GFP
      (vector control), Ad/gTRAIL (positive control), and Ad/TRAIL-F/RGD. Phosphate
      buffered saline (PBS) was used as control. Cell viability was determined by
      proliferation assay (XTT), and apoptosis induction by fluorescence activated cell
      sorting (FACS). RESULTS: Cells treated with Ad/TRAIL-F/RGD and Ad/gTRAIL showed a
      significantly reduced cell viability in comparison to PBS and Ad/CMV-GFP
      treatment in both cell lines. Whereas, treatment with PBS and Ad/CMV-GFP had no
      cell-killing effect. The reduced cell viability was caused by induction of
      apoptosis as shown by FACS analysis. The amount of apoptotic cells was similar
      after incubation with Ad/gTRAIL and Ad/TRAIL-F/RGD. CONCLUSION: The new RGD
      modified vector Ad/TRAIL-F/RGD could become a potent therapeutic agent for the
      treatment of HCC, adenovirus resistant tumors, and CAR low or negative cancer
      cells.

PMID- 15849811
TI  - Involvement of fatty acid-CoA ligase 4 in hepatocellular carcinoma growth: roles
      of cyclic AMP and p38 mitogen-activated protein kinase.
AB  - AIM: Fatty acid-CoA ligase 4 (FACL4) is an arachidonate-preferring enzyme which
      has been shown to be up-regulated in human colon cancer tissues and implicated in
      the colon tumorigenesis. The purpose of this study was to investigate the role of
      FACL4 in the human hepatocellular carcinoma (HCC) tumorigenesis and the specific
      signal pathways involved in this process. METHODS: We investigated the expression
      and regulation of FACL4 in HCC, adjacent non-tumorous liver tissues, and cell
      lines. RESULTS: In HCC patients, we demonstrated that FACL4 gene expression was
      markedly elevated in the cancerous tissues than in the adjacent non-cancerous
      liver tissues. In addition, several human hepatoma cell lines, including Hep3B
      and HepG2, expressed high levels of FACL4. Stable overexpression of FACL4
      knockdown plasmids (small interfering RNA, siRNA) to Hep3B cells significantly
      decreased FACL4 expression and subsequently limited the cell proliferation.
      Treatment of Hep3B cells with 8-bromo-cAMP and SB203508 (p38 MAPK inhibitor)
      significantly suppressed the FACL4 expression. CONCLUSION: FACL4 is involved in
      the HCC tumorigenesis and both cAMP and p38 MAPK pathways are associated with the
      regulation of FACL4 in HCC.

PMID- 15849812
TI  - Alpha-fetoprotein triggers hepatoma cells escaping from immune surveillance
      through altering the expression of Fas/FasL and tumor necrosis factor related
      apoptosis-inducing ligand and its receptor of lymphocytes and liver cancer cells.
AB  - AIM: To investigate the mechanism of alpha-fetoprotein (AFP) in escaping from the
      host immune surveillance of hepatocellular carcinoma. METHODS: AFP purified from
      human umbilical blood was administrated into the cultured human lymphoma Jurkat T
      cell line or hepatoma cell line, Bel7402 in vitro. The expression of tumor
      necrosis factor related apoptosis-inducing ligand (TRAIL) and its receptor
      (TRAILR) mRNA were analyzed by Northern blot and Western blot was used to detect
      the expression of Fas and Fas ligand (FasL) protein. RESULTS: AFP (20 mg/L) could
      promote the expression of FasL and TRAIL, and inhibit the expression of Fas and
      TRAILR of Bel7402 cells. For Jurkat cell line, AFP could suppress the expression
      of FasL and TRAIL, and stimulate the expression of Fas and TRAILR. AFP also could
      synergize with Bel7402 cells to inhibit the expression of FasL protein and TRAIL
      mRNA in Jurkat cells. The monoclonal antibody against AFP (anti-AFP) could
      abolish these functions of AFP. CONCLUSION: AFP is able to promote the expression
      of FasL and TRAIL in hepatoma cells and enhance the expression of Fas and TRAILR
      in lymphocytes. These could elicit the escape of hepatocellular carcinoma cells
      from the host's lymphocytes immune surveillance.

PMID- 15849813
TI  - Colonic J-pouch anal anastomosis after ultralow anterior resection with upper
      sphincter excision for low-lying rectal cancer.
AB  - AIM: There is some evidence of functional superiority of colonic J-pouch over
      straight coloanal anastomosis (CAA) in ultralow anterior resection (ULAR) or
      intersphincteric resection. On the assumption that colonic J-pouch anal
      anastomosis is superior to straight CAA in ULAR with upper sphincter excision
      (USE: excision of the upper part of the internal sphincter) for low-lying rectal
      cancer, we compare functional outcome of colonic J-pouch vs the straight CAA.
      METHODS: Fifty patients of one hundred and thirty-three rectal cancer patients in
      whom lower margin of the tumors were located between 3 and 5 cm from the anal
      verge received ULAR including USE from September 1998 to January 2002. Patients
      were randomized for reconstruction using either a straight (n = 26) or a colonic
      J-pouch anastomosis (n = 24) with a temporary diverting-loop ileostomy. All
      patients were followed-up prospectively by a standardized questionnaire (Fecal
      Incontinence Severity Index (FISI) scores and Fecal Incontinence Quality of Life
      (FIQL) scales). RESULTS: We found that, compared to straight anastomosis
      patients, the frequency of defecation was significantly lower in J-pouch
      anastomosis patients for 10 mo after ileostomy takedown. The FISI scores and FIQL
      scales were significantly better in J-pouch patients than in straight patients at
      both 3 and 12 mo after ileostomy takedown. Furthermore, we found that FISI scores
      highly correlated with FIQL scales. CONCLUSION: This study indicates that colonic
      J-pouch anal anastomosis decreases the severity of fecal incontinence and
      improves the quality of life for 10 mo after ileostomy takedown in patients
      undergoing ULAR with USE for low-lying rectal cancer.

PMID- 15849814
TI  - Anti-HBV activity of TRL mediated by recombinant adenovirus.
AB  - AIM: To investigate the inhibitive effect of hepatitis B virus (HBV)-TRL on HBV
      replication. METHODS: Based on previously constructed pcDNA3.1(-)/TRL, TR, TRmut,
      HBV core protein (HBVc) and hEDN, interest gene sequences TRL, TR, HBVc and hEDN
      were inserted into adenovirus shuttle plasmid pDC316 respectively and co
      transfected HEK293 cells with rescue plasmid pBHGloxdeltaE1,3Cre to acquire
      RAd/TRL, TR, HBVc and hEDN. And then RAds were identified, amplified and the
      titers in HEK293 cells were determined. RAd/TRL and TR were named as the
      experimental groups, and others were control ones. After HepG2.2.15 cells were
      infected, RAd/TRL expression was identified by indirect immunofluorescence
      staining. Supernatant HBV-DNA content was determined by fluorescent
      quantification PCR. Meanwhile, metabolism of HepG2.2.15 cells was evaluated by
      MTT colorimetry. RESULTS: RAd vectors with distinct interest gene sequence were
      successfully constructed. Effective expression of RAd/TRL in HepG2.2.15 cells
      resulted in a significant decrease of supernatant HBV-DNA content compared to
      RAd/TR (0.63+/-0.14 vs 1.60+/-0.47, P = 0.0266, <0.05) and other control groups
      (0.63+/-0.14 vs 8.50+/-2.78, 8.25+/-2.26, 8.25+/-2.29, 8.50+/-1.51, 8.57+/-1.63,
      P<0.01). MTT assay suggested that there were no significant differences in cell
      metabolic activity between groups (P>0.05). CONCLUSION: The construction and
      expression of RAd/TRL has been achieved and it could inhibit HBV replication
      successfully, which has laid the foundation for further research on anti-HBV
      activity in vivo.

PMID- 15849815
TI  - Effect of normothermic liver ischemic preconditioning on the expression of
      apoptosis-regulating genes C-jun and Bcl-XL in rats.
AB  - AIM: To explore the expression of apoptosis-regulating genes C-jun and Bcl-XL
      after normothermic liver ischemic preconditioning and its protective effect on
      hepatocytes in the rat. METHODS: Wistar rats are randomly divided into sham
      operation group (S group, n = 10), ischemic reperfusion group (IR group, n = 10)
      and ischemic preconditioning group (IP group, n = 10). After dissection of the
      hepatoduodenal ligament in S group, and after 30-min reperfusion in IR group and
      in IP group, the samples of liver tissue were taken for studying the
      hepatocellular apoptosis, the expressions of C-jun mRNA, Bcl-XL mRNA and their
      proteins, and morphologic changes at 0, 3, 6, 20 h. Meanwhile the venous blood
      samples were drawn at 3, 6 and 20 h for testing ALT, AST and LDH. RESULTS: The
      levels of ALT, AST and LDH in IR group and IP group were significantly higher
      than those in S group. Hepatocellular apoptosis was significantly increased in
      both IR group and IP group, especially in IR group. Expressions of C-jun mRNA and
      protein were significantly increased in IR group compared with those in both IP
      group and S group, but no significant difference between IP group and S group
      (P>0.05). Expressions of Bcl-XL mRNA and protein in IR group and S group were not
      significant (P>0.05), but were significantly increased in IP group compared with
      those in both S group and IR group. Patch necrosis of hepatocytes because of
      severe injury could be seen in IR group microscopically, and the ultrastructural
      changes were irreversible. Meanwhile in IP group, no hepatocellular necrosis
      occurred, and the ultrastructural changes were reversible because of mild injury.
      CONCLUSION: (1) IP can protect the rat liver from normothermic IR injury by
      modulation of the expression of apoptosis-regulating genes C-jun and Bcl-XL; (2)
      IR injury may activate the apoptosis of hepatocytes by increasing the expression
      of apoptosis-inducing gene C-jun; (3) IP may prohibit the apoptosis of
      hepatocytes by increasing the expression of apoptosis-inhibitory gene Bcl-XL.

PMID- 15849816
TI  - Efficacy of Chinese medicine Yi-gan-kang granule in prophylaxis and treatment of
      liver fibrosis in rats.
AB  - AIM: To investigate the efficacy of a Chinese medicine, Yi-gan-kang granule
      (granules for benefiting the liver), in prophylaxis and treatment of liver
      fibrosis in rats and its possible mechanism. METHODS: One hundred and forty
      Sprague-Dawley rats were randomly divided into seven groups (20 each): group 1,
      blank control group without any interference during the study; group 2, CCl4
      induced liver fibrosis group; group 3, pig serum-induced liver fibrosis group;
      group 4, prophylaxis group of CCl4-induced liver fibrosis by Yi-gan-kang; group
      5, prophylaxis group of pig serum-induced liver fibrosis by Yi-gan-kang; group 6,
      treatment group of CCl4-induced liver fibrosis by Yi-gan-kang; group 7, treatment
      group of CCl4-induced liver fibrosis by Yi-gan-kang. At wk 6, 10, 14 and 20
      (baseline for CCl4 or big serum induction), five rats in each group were
      anesthetized and their livers were removed for pathological studies including
      immunohistochemical studies for alpha-SMA, type I collagen and in situ
      hybridization of tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA of hepatic
      stellate cells (HSCs). Anti-lipid peroxidation in isolated mitochondria and 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric
      assay for proliferation and terminal deoxynucleotidyl transferase-medicated dUTP
      biotin nick end-labeling (TUNEL), flow cytometry and electron microscopy for
      apoptosis in isolated HSCs were also studied. RESULTS: The mean number of
      pseudolobuli at wk 10, 14 and 20 in the prophylaxis group was significantly less
      than that in the control group (P<0.05 or 0.01). The effect of prophylaxis at wk
      14 in CCl4 rats and at wk 10 in pig serum-induced rats was much better than that
      of treatment group (P<0.01). The thickness (in microm) of fibers both in pig
      serum-induced prophylaxis and in treatment groups at wk 14 and 20 was
      significantly less than that in control group (P<0.05). The number of fibers both
      in prophylaxis and in treatment groups from wk 10 or 14 to 20 was significantly
      less than that in control group (P<0.05 or P<0.01). The tissue HSC positive rates
      of type I collagen, alpha-SMA and TIMP-1 mRNA, which represented the active
      phenotype of HSCs in tissues, remained very high from wk 6 to the end of model
      making in control group. While in prophylaxis group, they were at a relatively
      low level. In treatment group, there was a gradual decreasing trend. Time- and
      dose-dependent effects of anti-lipid peroxidation on isolated mitochondria, cell
      proliferation and apoptosis in cultured HSCs were also observed during the study.
      CONCLUSION: Yi-gan-kang can effectively inhibit or inverse the course of liver
      fibrogenesis in CCl4- and pig serum-induced rat models.

PMID- 15849817
TI  - Effect of lactobacillus on the gut microflora and barrier function of the rats
      with abdominal infection.
AB  - AIM: To investigate the effect of probiotics supplemented by gut on the tight
      junctions of epithelial cells, barrier function and the microflora of rats with
      abdominal infection. METHODS: After the model of cecal ligation and perforation
      established, SD rats were divided into two groups: parenteral nutrition (PN)
      group and PN+probiotics (probiotics) group, PN solution was supplemented by neck
      vein and probiotics was delivered via the jejunostomy tube for five days. Vena
      cava blood and the homogenated tissue of liver, lung and mesenteric lymph nodes
      were cultured to determine the bacterial translocation rate (BTR). The ultra
      structure of epithelial tight junctions and microvilli of the gut were observed
      by electron microscopy; occluding expression was measured by indirect-immune
      fluorescence method; anaerobic bacterial growth by anaerobic culture and DNA
      fingerprint of bacterial colonies of the feces by PCR. RESULTS: The quantity of
      lactobacteria and bifydobacteria in probiotics group was higher than that of PN
      group. The profiles of DNA fingerprint expression in probiotics group were
      similar to that in the normal group, a new 16S rDNA sequence appeared in the
      profile in PN group. The occludin expression, the integrality of the gut
      epithelial tight junction and microvilli in probiotics group were improved as
      compared with PN group. The BTR and endotoxin in blood were reduced more
      significantly in probiotics group as compared with PN group. CONCLUSION: The
      probiotics could improve the gut microflora disturbance, increase occludin
      expression, maintain the gut epithelial tight junction and decrease the bacterial
      translocations rate.

PMID- 15849818
TI  - Construction, expression and characterization of human interferon alpha2b-(G4S)n
      thymosin alpha1 fusion proteins in Pichia pastoris.
AB  - AIM: Interferon alpha2b (IFNalpha2b) and thymosin alpha1 (Talpha1) exhibit
      synergic effects in the treatment of hepatitis B and hepatitis C when used
      together. For developing a fusion protein drug, fusion proteins of IFNalpha2b and
      Talpha1 linked by different lengths of (G4S)n (n = 1-3) were constructed and
      expressed in Pichia pastoris. METHODS: Using PCR and molecular clone techniques,
      the fusion genes of IFNalpha2b-(G4S)n-Talpha1 (n = 1-3) were constructed and
      subcloned into the eukaryotic expression vector pPIC9. After transformation of
      these plasmids into P. pastoris, the expressed fusion proteins IFNalpha2b-(G4S)n
      Talpha1 (n = 1-3) were obtained. These proteins were purified through
      diethylaminoethyl (DEAE) affinity chromatography and Superdex 75 gel filtration
      and analyzed by SDS-PAGE and Western blot. Antiviral and E-rosette assays were
      used to investigate the bioactivities of these fusion proteins. RESULTS: DNA
      sequencing confirmed that the fusion genes of IFNalpha2b-(G4S)n-Talpha1 (n = 1-3)
      were correctly cloned to the pPIC9 vector. The recombinant IFNalpha2b-(G4S)n
      Talpha1 (n = 1-3) fusion proteins expressed in P. pastoris were purified with
      DEAE and Superdex 75 gel filtration chromatography. The fusion proteins could be
      observed on sodium dodecylsulfate-polyacrylamide gel electrophoresis with
      molecular weight (MW) of 23.2, 22.9, and 22.6 ku, respectively, and reacted to
      the IFNalpha2b monoclonal antibody and Talpha1 polyclonal antibody. The purified
      fusion proteins exhibit antiviral activity and can enhance the percentage of E
      rosette-forming-cell in E-rosette assay. CONCLUSION: The recombinant IFNalpha2b
      (G4S)n-Talpha1 (n = 1-3) fusion proteins were successfully expressed in P.
      pastoris. Purified fusion proteins exhibit both antiviral activity of IFNalpha2b
      and immunomodulatory activity of Talpha1 in vitro. These results will be the
      basis for further evaluation of the fusion proteins' function in vivo.

PMID- 15849819
TI  - Effects of long-term ethanol consumption on jejunal lipase and disaccharidase
      activities in male and female rats.
AB  - AIM: To study the effect of long-term ethanol consumption on jejunal lipase and
      disaccharidase (sucrase, maltase, and lactase) activities in rats and its gender
      difference. METHODS: Age-matched male and female Wistar rats were fed control or
      ethanol-containing liquid diets for 12 wk following the Lieber-DeCarli model.
      According to both the plasma aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) activities, 40 rats were divided into four groups as
      follows: male control group (MC), male ethanol group (ME), female control group
      (FC), and female ethanol group (FE). RESULTS: After ethanol feeding for 12 wk,
      the results revealed that plasma AST and ALT activities of group ME were
      significantly increased by 58% and 92%, respectively, than those of group MC
      (P<0.05). Similarly, plasma AST and ALT activities of group FE were also
      significantly increased by 61% and 188%, respectively, than those of group FC
      (P<0.05). Fat accumulation was observed in both ethanol-treated groups, while
      fatty changes were more severe in group FE than those in group ME. The induction
      of hepatic microsomal cytochrome P450 2E1 (CYP2E1) was obviously seen in group ME
      and group FE, but was not detected in group MC and group FC. Jejunal lipase
      activity of group ME was significantly increased by 1.25-fold than that of group
      MC (P<0.05). In contrast to, sucrase, maltase, and lactase activities of group ME
      were significantly decreased by 63%, 62% and 67%, respectively, than those of
      group MC (P<0.05). Similarly, activities of these three enzymes of group FE were
      also significantly decreased by 43%, 46% and 52%, respectively, than those of
      group FC (P<0.05). There were no significant epithelial changes of the duodenal
      mucosa in any group. CONCLUSION: Long-term ethanol consumption significantly can
      increase jejunal lipase and decrease jejunal disaccharidase activities in both
      male and female rats.

PMID- 15849820
TI  - Construction and characterization of chimeric BHIV (BIV/HIV-1) viruses carrying
      the bovine immunodeficiency virus gag gene.
AB  - AIM: To explore the possibility of the replacement of the gag gene between human
      immunodeficiency virus and bovine immunodeficiency virus, to achieve chimeric
      virions, and thereby gain a new kind of AIDS vaccine based on BHIV chimeric
      viruses. METHODS: A series of chimeric BHIV proviral DNAs differing in the
      replacement regions in gag gene were constructed, and then were transfected into
      293T cells. The expression of chimeric viral genes was detected at the RNA and
      protein level. The supernatant of 293T cell was ultra centrifuged to detect the
      probable chimeric virion. Once the chimeric virion was detected, its biological
      activities were also assayed by infecting HIV-sensitive MT4 cells. RESULTS: Four
      chimeric BHIV proviral DNAs were constructed. Genes in chimeric viruses expressed
      correctly in transfected 293T cells. All four constructs assembled chimeric
      virions with different degrees of efficiency. These virions had complete
      structures common to retroviruses and packaged genomic RNAs, but the cleavages of
      the precursor Gag proteins were abnormal to some extent. Three of these virions
      tested could attach and enter into MT4 cells, and one of them could complete the
      course of reverse transcription. Yet none of them could replicate in MT4 cells.
      CONCLUSION: The replacement of partial gag gene of HIV with BIV gag gene is
      feasible. Genes in chimeric BHIVs are accurately expressed, and virions are
      assembled. These chimeric BHIVs (proviral DNA together with virus particles) have
      the potential to become a new kind of HIV/AIDS vaccine.

PMID- 15849822
TI  - Clinical and dosimetric factors of radiation-induced esophageal injury: radiation
      induced esophageal toxicity.
AB  - AIM: To analyze the clinical and dosimetric predictive factors for radiation
      induced esophageal injury in patients with non-small-cell lung cancer (NSCLC)
      during three-dimensional conformal radiotherapy (3D-CRT). METHODS: We
      retrospectively analyzed 208 consecutive patients (146 men and 62 women) with
      NSCLC treated with 3D-CRT. The median age of the patients was 64 years (range 35
      87 years). The clinical and treatment parameters including gender, age,
      performance status, sequential chemotherapy, concurrent chemotherapy, presence of
      carinal or subcarinal lymph nodes, pretreatment weight loss, mean dose to the
      entire esophagus, maximal point dose to the esophagus, and percentage of volume
      of esophagus receiving >55 Gy were studied. Clinical and dosimetric factors for
      radiation-induced acute and late grade 3-5 esophageal injury were analyzed
      according to Radiation Therapy Oncology Group (RTOG) criteria. RESULTS: Twenty
      five (12%) of the two hundred and eight patients developed acute or late grade 3
      5 esophageal injury. Among them, nine patients had both acute and late grade 3-5
      esophageal injury, two died of late esophageal perforation. Concurrent
      chemotherapy and maximal point dose to the esophagus > or =60 Gy were
      significantly associated with the risk of grade 3-5 esophageal injury. Fifty-four
      (26%) of the two hundred and eight patients received concurrent chemotherapy.
      Among them, 25 (46%) developed grade 3-5 esophageal injury (P = 0.0001<0.01).
      However, no grade 3-5 esophageal injury occurred in patients who received a
      maximal point dose to the esophagus <60 Gy (P = 0.0001<0.01). CONCLUSION:
      Concurrent chemotherapy and the maximal esophageal point dose > or =60 Gy are
      significantly associated with the risk of grade 3-5 esophageal injury in patients
      with NSCLC treated with 3D-CRT.

PMID- 15849821
TI  - Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic
      anhydrases IX and XII in normal and neoplastic colorectal mucosa.
AB  - AIM: To analyze possible relationships between CA IX/CA XII and pVHL expression
      in normal and neoplastic colorectal mucosa. METHODS: Immunohistochemical staining
      of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate
      the distribution and semi-quantitatively assess the levels of CA IX, CA XII and
      pVHL. VHL mRNAs from 14 fresh-frozen tumors was amplified by RT-PCR and subjected
      to sequencing. CA9 and CA12 mRNA levels were analyzed by semi-quantitative RT-PCR
      in comparison with VEGF as an indicator of hypoxia that uncouples the pVHL
      control. RESULTS: Tumor tissues were associated with a borderline increase of CA
      IX staining signal and slight but significant decrease of CA XII
      immunoreactivity, whereas no association was found for pVHL. Sequence analysis of
      RT-PCR-amplified VHL mRNAs revealed no deletions/mutations, suggesting that they
      were VHL-competent. We did not observe any correlation between pVHL and CA IX/CA
      XII proteins as well as between VEGF and CA9 mRNAs, but the tumor-associated
      changes in mRNA levels of VEGF and CA12 showed a significant inverse
      relationship. CONCLUSION: Our results indicate that CA9 and CA12 are regulated by
      different intratumoral factors and that lack of apparent relationship between the
      levels of CA IX/CA XII and pVHL cannot be fully assigned to uncoupling of
      negative regulatory function of pVHL by tumor hypoxia signified by induced VEGF
      transcription. The interplay between the functional pVHL and CA IX/CA XII in
      colorectal tumors seems rather complex and is not evident merely at the
      expression levels.

PMID- 15849823
TI  - Epidemiological characteristics of inflammatory bowel disease in North-Eastern
      Poland.
AB  - AIM: To provide the clinical and epidemiological data of inflammatory bowel
      disease (IBD) patients of North-Eastern Poland. METHODS: A total of 248 IBD
      patients diagnosed and hospitalized in the Department of Infectious Diseases in
      Bialystok between 1990 and 2003 were included in the study. We analyzed age, sex,
      education, characteristics of job, type of the environment, discontinuation of
      employment due to IBD, colitis extent, need of surgical treatment, and
      coexistence of other diseases. RESULTS: Two hundred and thirty-three IBD patients
      (94%) were diagnosed as ulcerative colitis (UC), and only 15 (6%) were diagnosed
      as Crohn's disease (CD). Patients with CD were significantly younger at the time
      of diagnosis and male predominance was observed. The mean age of the patients at
      the time UC diagnosis was 44.9+/-1.1 years. Histogram of the age of patients
      showed the characteristic biphasic distribution with two peaks between 20 and 40
      years and between 60 and 70 years. The predominant form of UC was left sided
      colitis, which affected almost 80% of the studied population. The most extensive
      form--pancolitis was present in 34 patients (15%). Only 6% of UC patients
      required surgery, whereas 36% of CD patients underwent surgery (P<0.005). Among
      coexisting disorders, cholelithiasis was the most prevalent and demonstrated in
      35 patients (14%), pulmonary disorders were diagnosed in 2%, and psoriasis in
      1.4%. Since 1998, the number of admitted IBD patients has slightly increased.
      CONCLUSION: Occurrence of UC in Poland is much higher than that of CD. The
      majority of UC cases are diagnosed in young people (20-40 years) with the
      predominance of male patients. The most common clinical form of UC is left sided
      colitis.

PMID- 15849824
TI  - Effects of interferon-alpha on expression of hepatic stellate cell and
      transforming growth factor-beta1 and alpha-smooth muscle actin in rats with
      hepatic fibrosis.
AB  - AIM: To investigate the effect of interferon-alpha (IFN-alpha) on preventing or
      reversing hepatic fibrosis in rat experimental model induced by CCl(4). METHODS:
      One hundred and ten Sprague-Dawley rats were divided into five groups: group A
      (normal controls, n=18), group B (fibrotic model controls, n = 22), group C (IFN
      alpha prevention, n=22) initially treated with intra-muscular injection of IFN
      alpha in saline daily at the doses of 1X105 U for 6 wk, group D (IFN-alpha
      treatment, n = 24) treated with intra-muscular injection of IFN-alpha in saline
      daily at the doses of 1X105 U for 6 wk after the first 6 wk, group E (0.9% sodium
      chloride treatment control, n = 24) treated with intra-muscular injection of 0.01
      mL/kg daily for 6 wk after the first 6 wk. At the end of the experiment, all rats
      of each group were killed. Samples of the liver obtained by biopsy were subjected
      to histological, immunohistochemical and electron microscopic studies for the
      expressions of transforming growth factor-beta1 (TGF-beta1) and alpha-smooth
      muscle actin (alpha-SMA). RESULTS: The expressions of TGF-beta1, the number of
      activated hepatic stellate cells and alpha-SMA in hepatic tissue of group C were
      significantly less than those of group B (P<0.01). The degree of fibrosis score
      in group B was also significantly less than that of group C under light
      microscope (P<0.01). CONCLUSION: IFN-alpha can inhibit the production of TGF
      beta1, decrease HSC activation and stimulate its apoptosis.

PMID- 15849826
TI  - Anti-hepatocarcinoma effects of 5-fluorouracil encapsulated by galactosylceramide
      liposomes in vivo and in vitro.
AB  - AIM: To study the anti-hepatocarcinoma effects of 5-fluorouracil (5-Fu)
      encapsulated by galactosylceramide liposomes (5-Fu-GCL) in vivo and in vitro.
      METHODS: Tumor-bearing animal model and HepA cell line were respectively adopted
      to evaluate the anti-tumor effects of 5-Fu-GCL in vivo and in vitro. Tumor cell
      growth inhibition effects of 5-Fu-GCL in vitro were assessed by cell viability
      assay and MTT assay. In vivo experiment, the inhibitory effects on tumor growth
      were evaluated by tumor inhibition rate and animal survival days. High
      performance liquid chromatography was used to detect the concentration-time
      course of 5-Fu-GCL in intracellular fluid in vitro and the distribution of 5-Fu
      GCL in liver tumor tissues in vivo. Apoptosis and cell cycle of tumor cells were
      demonstrated by flow cytometry. RESULTS: In vitro experiment, 5-Fu-GCL (6.25-100
      micromol/L) and free 5-Fu significantly inhibited HepA cell growth. Furthermore,
      IC50 of 5-Fu-GCL (34.5 micromol/L) was lower than that of free 5-Fu (51.2
      micromol/L). In vivo experiment, 5-Fu-GCL (20, 40, 80 mg/kg) significantly
      suppressed the tumor growth in HepA bearing mice model. Compared with free 5-Fu,
      the area under curve of 5-Fu-GCL in intracellular fluid increased 2.6 times.
      Similarly, the distribution of 5-Fu-GCL in liver tumor tissues was significantly
      higher than that of free 5-Fu. After being treated with 5-Fu-GCL, the apoptotic
      rate and the proportion of HepA cells in the S phase increased, while the
      proportion in the G0/G1 and G2/M phases decreased. CONCLUSION: 5-Fu-GCL appears
      to have anti-hepato-carcinoma effects and its drug action is better than free 5
      Fu. Its mechanism is partly related to increased drug concentrations in
      intracellular fluid and liver tumor tissues, enhanced tumor cell apoptotic rate
      and arrest of cell cycle in S phase.

PMID- 15849825
TI  - Influential factors and formation of extrahepatic collateral artery in
      unresectable hepatocellular carcinoma.
AB  - AIM: To analyze the influence factors and formation of extrahepatic collateral
      arteries (ECAs) in unresectable hepatocellular carcinoma (HCC) with or without
      chemoembolization. METHODS: Detailed histories of 35 patients with 39 ECAs of HCC
      and images including computerized tomography scan, digital subtraction
      angiography were reviewed carefully to identify ECAs of HCC, ECAs arising from,
      and anatomic location of tumors in liver. Tumor sizes were measured, and
      relations of ECAs with times of chemoembolization, tumor size, and the anatomic
      tumor location were analyzed. Complications were observed after chemoembolization
      through ECAs of HCC with different techniques. RESULTS: Influence factors of
      formation of ECAs of HCC included the times of repeated chemoembolization, the
      location of tumors in liver, the tumor size and the types of chemoembolization.
      ECAs in HCC appeared after 3-4 times of chemoembolization (17.9%), but a higher
      frequency of ECAs occurred after 5-6 times of chemoembolization (56.4%). ECAs
      presented easily in peripheral areas (71.8%) of liver abutting to the anterior,
      posterior abdominal walls, the top right of diaphragm and right kidney. ECAs also
      occurred easily after complete obstruction of the trunk arteries supplying HCCs
      or the branches of proper hepatic arteries. Extrahepatic collaterals of HCC
      originated from right internal thoracic (mammary) artery (RITA, 5.1%), right
      intercostal artery (RICA, 7.7%), left gastric artery (LGA, 12.8%), right inferior
      phrenic artery (RIPA, 38.5%), omental artery (OTA, 2.6%), superior mesenteric
      artery (SMA, 23.1%), and right adrenal and renal capsule artery (RARCA, 10.3%),
      respectively. The complications after chemoembolization attributed to no super
      selective catheterization. CONCLUSION: The formation of ECAs in unresectable HCC
      is obviously correlated with multiple chemoembolization, tumor size, types of
      chemoembolization, anatomic location of tumors. Extrahepatic collaterals in HCC
      are corresponding to the tumor locations in liver.

PMID- 15849827
TI  - Restriction fragment length polymorphism of adhesin gene hpaA from different
      Helicobacter pylori strains of Chongqing, China.
AB  - AIM: To assess the variability of adhesin gene hpaA between different
      Helicobacter pylori (H pylori) strains with PCR-restriction fragment length
      polymorphism (RFLP). METHODS: Twelve different H pylori strains were chosen to
      amplify the 710-bp segments of gene hpaA. These strains were NCTC11637, SS1;
      Chongqing clinical isolates CCS9801, CCS9802, CCS9803, CCS9806, CCS9809, CCS9810,
      CCS9813, which were gained from patients of gastritis; Mongolia gerbil adapted H
      pylori strains (abbreviation MG), which were gained from the following steps:
      gastric mucosal specimens of Mongolia gerbils infected by clinical isolate
      CCS9803 were cultured and detected, the positive H pylori strains were named as
      the first generation of Mongolia gerbil adapted H pylori strains (abbreviation
      MG1) and then were subcultured with healthy Mongolia gerbil to generate MG2, in
      turn to gain the ninth generation (abbreviation MG9). All hpaA segments, obtained
      from 12 different H pylori strains, were digested by HhaI and HaeIII individually
      and analyzed by agarose gel electrophoresis. RESULTS: In all 12 strains, the 710
      bp PCR products were successfully amplified and products were cloned to pMD18-T
      vector respectively, then the recombinant plasmids were digested simultaneously
      with NcoI and XhoI to recover the small fragments. The objective fragments from
      12 different H pylori strains digested with Hae III could be seen as 4 types of
      bands and 5 types with Hha I. According to the hpaA RFLP patterns, the 12 H
      pylori strains could be divided into 5 groups: group I, NCTC11637 and SS1; group
      II, CCS9809, which RFLP type digested with HaeIII was the same as strains of
      group I, but HhaI RFLP showed difference compared with the other groups; group
      III, CCS9810; group IV, CCS9803; group V: CCS9801, CCS9802, CCS9806, CCS9813,
      MG1, MG3 and MG9. The sequence data of 12 hpaA segments were analyzed by DNAsis
      software and it was observed that: (1) The homologies of base pair and amino acid
      sequence between strains NCTC11637, SS1, CCS9809 were 99.6% and 98.9%,
      respectively; (2) The homology of base pair and amino acid sequence between
      CCS9803 and CCS9810 was 97.7% and 99.1%; (3) That of the rest strains, CCS9801,
      CCS9802, CCS9806, CCS9813, MG1, MG3, MG9 reached 99.4% and 98.4%; (4) The base
      pair homologies between all hpaA fragments of different sources were higher than
      94.6%, therefore the correspondence of deduced amino acid sequence was higher
      than 96.8% between each other. CONCLUSION: The gene hpaA from different H pylori
      strains revealed variation, and this might provide an effective method for
      molecular epidemiological survey of H pylori.

PMID- 15849828
TI  - Transfection of apoptosis related gene Fas ligand in human hepatocellular
      carcinoma cells and its significance in apoptosis.
AB  - AIM: To evaluate the expression of apoptosis related gene Fas ligand (FasL) in
      human hepatocellular carcinoma (HCC) cells HepG2 and its significance in
      apoptosis. METHODS: Levels of soluble Fas ligand (sFasL) in a group of patients
      with hepatitis B virus (HBV)-induced chronic hepatitis, HBV-positive liver
      cirrhosis and HCC were evaluated. In a further study, the recombinant eukaryotic
      expression plasmid pcDNA3.1hisB-FasL was transfected into HCC cells HepG2 by
      lipofection, and then soluble FasL was examined in the supernatant of culture
      cells by EIA, FasL expression in HepG2 cells was detected by
      immunohistochemistry. After being stained by annexin V and propidium iodine,
      cells were passed through a flow cytometer and examined by a fluorescence
      microscope and a laser scanning microscope. RESULTS: The sFasL levels were
      significantly lower in patients with HCC when compared to the patients with
      hepatitis or liver cirrhosis. In comparison with untransfected cells, the soluble
      FasL could be detected in the supernatant of transfected cells. FasL was
      expressed on the membranes and cytoplasm of transfected cells. The apoptotic cell
      rate was 36.30% in transfected cells, and was 11.53% in untransfected cells.
      Moreover, the different stage of apoptotic cells could be distinguished by
      annexin V and propidium iodine staining. CONCLUSION: Fas ligand is an apoptotic
      pathway of HCC cells.

PMID- 15849829
TI  - Role of AFP mRNA expression in peripheral blood as a predictor for postsurgical
      recurrence of hepatocellular carcinoma: a systematic review and meta-analysis.
AB  - AIM: To identify the role of alpha-fetoprotein (AFP) mRNA expression in
      peripheral blood one week after surgery as a predictor for recurrence of
      hepatocellular carcinoma (HCC). METHODS: Published studies fulfilling the
      selection criteria were identified by searching several databases online. After a
      methodology assessment using a quality scale designed by European Lung Cancer
      Working Party, data in each research were aggregated by means of meta-analysis.
      RESULTS: Altogether 368 cases were included in the 9 selected studies, which
      fulfilled the selection criteria. The quality scores ranged from 35% to 84% with
      a median score of 55%. The 'design' subscore had the lowest median value (38%).
      By aggregating the data, a high chi2 value (77.576) was presented. The fail-safe
      number was 136 and 64 for P = 0.05 and 0.01, respectively. CONCLUSION: AFP mRNA
      expression in peripheral blood 1 wk after surgery correlated with the recurrence
      of HCC and was a good predictor for tumor recurrence.

PMID- 15849830
TI  - Dynamical changing patterns of glycogen and enzyme histochemical activities in
      rat liver graft undergoing warm ischemia injury.
AB  - AIM: To investigate the changing patterns of glycogen and enzyme histochemical
      activities in rat liver graft under a different warm ischemia time (WIT) and to
      predict the tolerant time limitation of the liver graft to warm ischemia injury.
      METHODS: The rats were randomized into five groups, WIT was 0, 15, 30, 45, 60
      min, respectively, and histochemical staining of liver graft specimens was
      observed. The recovery changes of glycogen and enzyme histochemistry activities
      were measured respectively 6 and 24 h following liver graft implantation.
      RESULTS: The activities of succinic dehydrogenase, cytochrome oxidase, apyrase
      (Mg++-ATPase) and content of glycogen were decreased gradually after different
      WIT in a time-dependent manner. The changes were significant when WIT was over 30
      min. CONCLUSION: Hepatic injury is reversible within 30 min of warm ischemia
      injury. Glycogen and enzyme histochemistry activities of liver grafts and their
      recovery potency after reperfusion may serve as criteria to evaluate the quality
      of liver grafts.

PMID- 15849831
TI  - Capability of multidetector CT to diagnose hepatocellular carcinoma-associated
      arterioportal shunt.
AB  - AIM: To investigate the capability of multidetector CT (MDCT) to diagnose HCC
      associated arterioportal shunt (APS). METHODS: Two hundred and eighty-two
      patients with HCC received both thin-slice and enhancement MDCT scanning at early
      hepatic arterial phase, late hepatic arterial phase and portal venous phase, and
      digital subtract angiography (DSA) examination. Images were analyzed jointly by
      two experienced radiologists blinded to the opposite examination results,
      including the existence or not of APS, shunt locations, types and degrees of APS,
      with or without thrombosis. RESULTS: There were 56 APS associated with HCC,
      including 48 central, seven peripheral and one mixed, or 42 severe, seven
      moderate, seven mild APS. Forty-one severe, seven moderate and central APS were
      all revealed with MDCT and DSA. Seven mild and peripheral APS were all displayed
      with MDCT; only five of them displayed DSA, two faint shunt APS associated with
      massive HCC were missed. One mixed APS was demonstrated as severe combined with
      mild shunt with both MDCT and DSA. CONCLUSION: MDCT could diagnose not only DSA
      revealed APS, but also missed mild and peripheral APS with DSA due to faint shunt
      associated with massive HCC, is a simple, effective and noninvasive new technique
      for diagnosis of HCC-associated APS.

PMID- 15849832
TI  - Effects of rhubarb on isolated gastric muscle strips of guinea pigs.
AB  - AIM: To study the effects of rhubarb (dried root of Rheum officinale Baill.) on
      contractile activity of isolated gastric muscle strips of guinea pigs and its
      possible mechanism. METHODS: A total of 48 guinea pigs were killed to remove the
      whole stomach. Then, the stomach was opened and the mucosal layer was removed.
      Parallel to the circular fibers, muscle strips were cut from the body. Each
      isolated gastric muscle strip was suspended in a tissue chamber containing 5 mL
      Krebs solution, constantly warmed by water jacket at 37 degrees and bubbled
      continuously with a mixed gas of 950 mL/L O2 and 50 mL/L CO2. After being
      incubated for 1 h with 1 g tension, rhubarb of varied concentrations (1%, 2%, 7%,
      20% and 70%) was added cumulatively into the tissue chamber at intervals of 2
      min. Atropine (10(-6) mol/L) or isoptin (5 x 10(-8) mol/L) or hexamethonium (10(
      5) mol/L) was given 2 min before the administration of rhubarb. The isometrical
      response was measured with an ink-writing recorder. RESULTS: Rhubarb dose
      dependently increased the resting tension of gastric body circular muscle (CM) (r
      = 0.726, P<0.05). Atropine (r = 0.829, P<0.05), isoptin (r = 0.764, P<0.05) and
      hexamethonium (r = 0.797, P<0.05) did not affect its action in a dose-related
      manner. Atropine apparently reduced the increasing action of 1%, 3%, 10%, 30% and
      100% rhubarb on the resting tension of gastric body CM. Isoptin inhibited the
      effect of 10%, 30% and 100% rhubarb on the resting tension of gastric body CM.
      Hexamethonium reduced the increasing action of 1%, 10%, 30% and 100% rhubarb on
      the resting tension of gastric body CM. Rhubarb increased the contractile
      frequency of CM of body. While atropine, isoptin and hexamethonium did not
      inhibit the contractile frequency of gastric body CM in comparison with rhubarb
      at the same concentration, rhubarb at the highest concentration (100%) decreased
      the mean contractile amplitude of gastric body CM. Atropine, isoptin and
      hexamethonium did not affect the mean contractile amplitude of gastric body CM
      compared to rhubarb at the same concentration. CONCLUSION: Rhubarb has exciting
      actions on isolated gastric smooth muscle strips of guinea pig. The exciting
      action of rhubarb is partly mediated via cholinergic M receptor, cholinergic N
      receptor and L-type calcium channel.

PMID- 15849833
TI  - Relationship between trefoil factor 1 expression and gastric mucosa injuries and
      gastric cancer.
AB  - AIM: To determine whether trefoil factor 1 (TFF1) is associated with mucosa
      healing and carcinoma suppression, we assess the expression of trefoil factor 1
      in normal and pathologic gastric mucosa. METHODS: TFF1 in normal and pathologic
      gastric mucosa was assessed by immunohistochemical method, and the average
      positive A was estimated by Motic Images Advanced 3.0 software. RESULTS:
      Increased TFF1 was detected in gastritis, gastric ulcer and duodenal ulcer
      compared with normal mucosa. The same result could be seen in multiple and
      compound ulcer compared with simple ulcer. There was no significant difference
      between gastric ulcer and duodenal ulcer, gastritis and simple ulcer
      respectively. Increased TFF1 was detected in the peripheral mucosa of the gastric
      adenocarcinoma compared with normal mucosa. The expression of TFF1 in gastric
      adenocarcinoma was related to the differentiation of adenocarcinoma. The lower
      the differentiation of adenocarcinoma, the weaker the expression of TFF1. There
      was no TFF1 expressed in low-differentiated adenocarcinoma. The expression of
      TFF1 in middle and highly differentiated adenocarcinoma was a little lower than
      that in normal mucosa. But there was no significant difference. No TFF1 was
      assessed in esophageal squamous carcinoma and peripheral tissue. There was no
      significant difference between male and female. CONCLUSION: The expression of
      TFF1 was higher in gastritis and peptic ulcer than that in normal mucosa, and was
      also higher in multiple and compound ulcer than in simple ulcer. It seems that
      TFF1 plays a role in gastric mucosa protection and epithelial restitution.
      Increased expression of TFF1 in peripheral tissue suggests that TFF1 is
      associated with mechanism of carcinoma suppression and differentiation. Decreased
      expression of TFF1 in carcinoma and its relativity to the differentiation
      suggests that TFF1 is related to gland and cell destruction of carcinoma.

PMID- 15849834
TI  - Endoscopic sphincterotomy in the treatment of cholangiopancreatic diseases.
AB  - AIM: To investigate the therapeutic effect of endoscopic sphincterotomy (EST) in
      the treatment of choledocholithiasis and stenosing papillitis. METHODS: A total
      of 1 026 patients undergoing EST during July 1983 to May 2003 at the institute
      were retrospectively analyzed. Chronic pancreatitis was diagnosed in 63 (6.1%),
      cholecystolithiasis and choledocholithiasis in 549 (53.5%), stones in residual
      biliary duct in 249 (24.3%), stenosing papillitis in 228 (22.2%). In patients
      with simple stenosing papillitis, most incisions were within 0.5-1 cm in length.
      As for patients with chronic pancreatitis simultaneously, selective pancreatic
      sphincterotomy was performed, and incision was within 0.5-0.8 cm in length. For
      stones less than 1 cm, incision was from 1 to 1.5 cm, and for those larger than 1
      cm, incision ranged from 1.5 to 3 cm. For stones more than 2 cm in diameter,
      detritus basket rather than simple incision was chosen. RESULTS: Of the 798
      patients with choledocholithiasis, 764 (93.5%) had successful stone clearance,
      215 (94.3%) out of 228 cases of stenosing papillitis were cured totally, while 63
      had chronic pancreatitis developed from stenosing papillitis, 57 (90.1%) had
      sound remission of symptoms, though membranous stenosis emerged in 13 of 57 which
      was treated with balloon dilatation. After the operation, only 21 cases (2.1%)
      had complications such as severe pancreatitis and incision bleeding. None of the
      patients died. CONCLUSION: EST is an ideal surgical management with mini-invasion
      in the treatment of choledocholithiasis and stenosing papillitis.

PMID- 15849835
TI  - Pseudomembranous colitis presenting as acute colonic obstruction without diarrhea
      in a patient with gastric Burkitt lymphoma.
AB  - Pseudomembranous colitis (PMC) usually manifests as fever and diarrhea in
      hospitalized patients treated with systemic antibiotics. We described a case of
      PMC with intestinal obstruction but without diarrhea. A 60-year-old man was
      hospitalized for chemotherapy for the treatment of Burkitt lymphoma of the
      stomach. The patient became febrile and complained of crampy abdominal pain
      during the post-chemotherapy nadir. Plain abdominal radiography showed some
      intestinal gas and niveau. Because stool cytotoxin assay for clostridium
      difficile was positive and colon fiberscopic examination showed a pseudomembrane
      at the left side of the colon, and a diagnosis of PMC was made. Treatment with
      intracolonic vancomycin administration by colonoscopy and nasoileus tube was
      successful. Physicians should take into account the possibility of bowel
      obstruction due to PMC occurring in patients undergoing chemotherapy and perform
      emergency colonoscopy examination of suspected cases.

PMID- 15849836
TI  - Polyvinyl alcohol and gelatin sponge particle embolization of splenic artery
      pseudoaneurysm complicating chronic alcoholic pancreatitis.
AB  - AIM: To assess the effectiveness of and complications associated with polyvinyl
      alcohol (PVA) and gelatin sponge particles embolization of splenic artery
      pseudoaneurysm complicating chronic alcoholic pancreatitis. METHODS: A 42-year
      old man with splenic artery pseudo-aneurysm formation secondary to chronic
      alcoholic pancreatitis was admitted. We used PVA and gelatin sponge particles
      embolization of splenic artery pseudoaneurysm by superselective embolization
      techniques. RESULTS: The splenic artery pseudoaneurysm was successfully
      controlled with splenic embolization. The patient was discharged in 9 d with
      complete recovery. CONCLUSION: This case confirms that superselective
      transcatheter embolization by PVA and gelatin sponge particles may represent an
      effective treatment for pseudoaneurysm caused by chronic alcoholic pancreatitis
      in the absence of other therapeutic alternatives.

PMID- 15849837
TI  - Perforation of metastatic melanoma to the small bowel with simultaneous
      gastrointestinal stromal tumor.
AB  - The gastrointestinal tract (GIT) is a common site of metastases for malignant
      melanoma. These metastatic tumors are often asymptomatic. We describe a case of a
      58-year-old male who presented with a sudden onset of generalized abdominal pain.
      The patient's past medical history was significant for lentigo melanoma of the
      right cheek. Laparotomy was performed and two segments of small bowel, one with a
      perforated tumor, the other with a non-perforated tumor, were removed. Histology
      and immunohistochemical staining revealed the perforated tumor to be a metastatic
      malignant melanoma and the non-perforated tumor was found to be a
      gastrointestinal stromal tumor (GIST). The patient was discharged 7 d
      postoperatively. To the best of our knowledge, this is the first reported case in
      the literature of a simultaneous metastatic malignant melanoma and a GIST.
      Surgical intervention is warranted in patients with symptomatic GIT metastases to
      improve the quality of life or in those patients with surgical emergencies.

PMID- 15849838
TI  - Control of bacterial pneumonia during mechanical ventilation.
AB  - Pneumonia complicates the course of 50% of patients on mechanical ventilation,
      requiring three or more days of mechanical ventilation and potentially increasing
      the relative risk of mortality by 20-40%. The predominant potentially pathogenic
      micro-organisms are Streptococcus pneumoniae, Staphylococcus aureus (sensitive to
      methicillin in the previously healthy host), Pseudomonas aeruginosa (aerobic gram
      negative bacilli), and methicillin-resistant Staphylococcus aureus in the host
      with underlying disease. Approximately 85% of pneumonias are endogenous, caused
      by bacteria present in the patient's oropharyngeal flora. Bacteria present on
      admission cause primary endogenous pneumonia (55%), whereas bacteria acquired in
      the unit lead to supercarriage or secondary carriage and subsequently secondary
      endogenous pneumonia (30%). The remaining 15% are exogenous, ie the bacteria
      causing pneumonia are not carried by the patient. The diagnosis is usually based
      on clinical, radiological, and microbiological criteria, using the non-invasive
      method of tracheal aspirate, which yields >/=10(5) micro-organisms. Seven
      randomized trials have evaluated three non-antibiotic prophylactic maneuvers:
      hygiene (1 trial), subglottic drainage (4 trials), and semirecumbent position (2
      trials). The impact on pneumonia was mixed, whereas mortality was unchanged.
      Selective digestive decontamination, using parenteral and enteral antimicrobials
      to control the three types of pneumonia, has been evaluated in 54 trials and
      showed an absolute mortality reduction of 8%. The therapy of pneumonia relies on
      six basic principles: (a) surveillance and diagnostic cultures to identify micro
      organisms; (b) immediate and adequate antibiotic treatment to sterilize the lower
      airways, (c) the source of potential pathogens requires elimination for recovery
      of the original infection and prevention of relapses and/or superinfections; (d)
      aerosolized antimicrobials; (e) removal or replacement of the endotracheal tube;
      and (f) surveillance samples are indispensable to monitor efficacy of treatment.
      The aim of our review was to evaluate up to date facts regarding control of
      bacterial pneumonias during mechanical ventilation in intensive care unit
      settings.

PMID- 15849839
TI  - Patient mobility in European Union: health spas in Ischia, Italy.
AB  - In a new case on patients seeking medical services abroad, the Leichtle case, the
      European Court of Justice (ECJ) confirmed its previous rulings on patient
      mobility. According to the Court, patients in the European Union have a
      (conditional) right to receive health care abroad, whereas the sickness fund
      should reimburse the costs of treatment and travel expenditures. As such, the
      Court has strengthened patient mobility in the European Union, based on the free
      movement principles. Now, it is up to the European Commission to develop a
      communal strategy aimed at further strengthening patients' rights in the Union.

PMID- 15849840
TI  - Antinociceptive effect of botulinum toxin type a in rat model of carrageenan and
      capsaicin induced pain.
AB  - AIM: To test antinociceptive properties of botulinum toxin type A (BTX-A) in rats
      with carrageenan- and capsaicin-induced pain and inflammation. METHODS: Pain was
      provoked with carrageenan (1%) or capsaicin (0.1%) injection into the plantar
      surface of the rat paw-pad. The effect of BTX-A 5 U/kg on carrageenan- and
      capsaicin-induced mechanical and thermal hypersensitivity, as well as the size of
      carrageenan-induced paw edema were tested 24 hours and 6 days following the toxin
      injection into the rat paw-pad. In the dose-response experiment, the effect of
      different doses of BTX-A (2, 3, 3.5, 5, and 7 U/kg) on carrageenan-induced
      mechanical hypersensitivity was investigated on day 5 after BTX-A application.
      RESULTS: Pretreatment with 5 U/kg BTX-A significantly reduced or completely
      abolished the enhanced sensitivity to mechanical and thermal stimuli provoked by
      peripheral carrageenan or capsaicin injections. This reduction was significant
      when BTX-A was applied 6 days before the induction of pain and inflammation, but
      the toxin was ineffective when applied 24 hours before the challenge. In the dose
      response experiment, the lowest effective dose was 3.5 U/kg, but apparently the
      effect was not dose-dependent. In contrast to the antinociceptive effect, 5 U/kg
      BTX-A had no effect on the carrageenan-induced paw edema. CONCLUSION: The study
      demonstrated the efficacy of peripherally applied BTX-A pretreatment on the pain
      component of inflammatory process in experimental animals.

PMID- 15849841
TI  - Exogenous surfactant administration by asymmetric high-frequency jet ventilation
      in experimental respiratory distress syndrome.
AB  - AIM: To evaluate the efficacy of surfactant administration using the instillation
      technique by means of asymmetric high-frequency jet ventilation (HFJV). METHODS:
      Experiments were carried out on tracheotomized, anaesthetized, and paralyzed
      rabbits. Animals were lung-lavaged with saline and conventionally ventilated with
      100% oxygen. After respiratory failure, they were ventilated for additional 2
      hours with conventional ventilation (f=30/min) or HFJV (f=300/min). Subgroups
      were treated with porcine surfactant (Curosurf; 80 mg/mL, dose 200 mg/kg) as a
      bolus followed by conventional ventilation or instilled into the jet of the
      ventilator during asymmetric HFJV (inspiration time Ti=30%). In controls, no
      material was instilled. RESULTS: Bolus administration of Curosurf followed by
      conventional ventilation in comparison with conventionally ventilated animals
      without surfactant improved gas exchange (at 60 minutes: PaO(2)/FiO(2), 9.8-/+3.6
      vs 22.3-/+8.5 kPa, P=0.020), reduced right-to-left pulmonary shunts (at 60
      minutes: 47.8-/+13.8 vs 23.9-/+6.7 %, P<0.006), and reduced inflammatory response
      in the lungs. Surfactant administration by HFJV in comparison with bolus
      instillation resulted in even better gas exchange (at 90 minutes: 20.7-/+8.8 vs
      39.1-/+10.9 kPa, P=0.005) and reduction of right-to-left pulmonary shunts (at 90
      minutes: 29.1-/+7.2 vs 8.0-/+2.2 %, P=0.008). High-frequency jet ventilation with
      or without surfactant treatment significantly increased pressure-volume
      recordings and reduced intraalveolar edema in comparison with conventional
      ventilation-only group. There were no significant differences in inflammatory
      response between the two tested methods. CONCLUSION: The response to surfactant
      therapy in experimental lung injury depends on the surfactant delivery method and
      may be potentiated by high-frequency jet ventilation.

PMID- 15849842
TI  - Effects of atenolol and propranolol on platelet aggregation in moderate essential
      hypertension: randomized crossover trial.
AB  - AIM: To compare the effects of a selective beta-blocker atenolol and a
      nonselective beta-blocker propranolol on platelet aggregation. METHODS: Twenty
      successive outpatients with moderate essential hypertension (6 women and 14 men,
      mean age-/+standard deviation 42.6-/+8.5 years) were randomized to either
      propranolol (40 mg three times a day) or atenolol (100 mg once a day) for the
      first two weeks, followed by a one-day washout period, and then a two-week
      administration of the alternative drug. Along with standard examinations and
      tests, circulating platelet aggregates were measured. RESULTS: There were no
      significant differences in creatinine, blood glucose, potassium, total
      cholesterol, hemoglobin, red blood cells (RBC), or platelets in three periods:
      baseline, atenolol, and propranolol period. Significant and comparable reductions
      in systolic and diastolic arterial pressure, body weight, heart rate, and HDL
      cholesterol were recorded in both patient groups. The LDL-cholesterol
      concentration increased significantly in propranolol compared with both baseline
      and atenolol period. Serum triglycerides increased significantly with both
      medications. The number of circulating platelet aggregates decreased
      significantly with propranolol (0.99-/+0.19) in comparison with both atenolol
      (1.41-/+0.70; P=0.004, Wilcoxon matched pairs test) and baseline (1.59-/+0.94;
      P=0.002, Wilcoxon matched pairs test). CONCLUSION: Propranolol inhibits platelet
      aggregation more than atenolol and may have a favorable effect on the management
      of hypertension especially in patients with increased cardiovascular risk.

PMID- 15849843
TI  - Non-insulin dependent diabetes as an independent predictor of asymptomatic left
      ventricular diastolic dysfunction.
AB  - AIM: To assess the prevalence of diastolic dysfunction of the left ventricle in
      patients with non-insulin-dependent diabetes mellitus (NIDDM) and its relation to
      patients' age and duration of diabetes. METHODS: This case-control study included
      228 subjects. The group of cases consisted of 114 patients with NIDDM. The group
      of controls included 114 subjects without diabetes, enrolled in the study at the
      same time as the group of cases. Diastolic function of the left ventricle was
      assessed by pulsed Doppler echocardiography. The ratio between the maximal early
      filling velocity (E wave) and the maximal late (atrial) filling velocity (A wave)
      less than 1 (E/A ratio<1) was considered as a criterion for left ventricle
      diastolic dysfunction. RESULTS: The E/A ratio<1 was found in 75 patients (65.8%)
      in the group with diabetes, and in 38 subjects (33.3%) in the control group
      (P=0.001). Multiple logistic regression model showed that diabetes was the
      strongest independent correlate of left ventricle diastolic dysfunction (odds
      ratio 8.92, 95% confidence interval [CI] 4.20 to 18.52, P<0.001). In the group
      with diabetes, the multivariate analysis showed that age (P=0.001), level of
      triglycerides (P=0.006), history of smoking (P=0.011), and the duration of
      diabetes (P=0.019) were independently associated with left ventricle diastolic
      dysfunction. CONCLUSIONS: Non-insulin dependent diabetes is an independent
      predictor of left ventricular diastolic dysfunction in patients without clinical
      evidence of structural heart disease. In patients with NIDDM, the age, history of
      smoking, plasma level of triglycerides, and the duration of diabetes were
      independently associated with the diastolic dysfunction of the left ventricle.

PMID- 15849844
TI  - Biochemical indicators and cardiac function tests in chronic alcohol abusers.
AB  - AIM: To determine the effect of chronic alcohol abuse on cardiac function,
      antioxidant system, trace elements, and liver function tests. METHODS: Mean
      corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl
      transferase (GGT), superoxide dismutase (SOD), malondialdehyde (MDA), as well as
      zinc, magnesium, and copper were assayed in 25 chronic alcoholic patients and
      their 25 healthy relatives matched in age and gender. Echocardiographic
      parameters were evaluated for subjects. RESULTS: Mean corpuscular volume (96.7 fL
      vs 92.4 fL) and mean corpuscular hemoglobin levels (31.4 pg vs 30.5 pg) were
      found to be significantly increased in the patient group (P=0.002 and P=0.048,
      respectively). The results of the SOD and MDA assays showed no significant
      differences between the two groups. AST (38.7 U/L vs 22.1 U/L) and GGT (104.2 U/L
      vs 34.2 U/L) levels were found to be significantly increased in the patient group
      compared with controls (P=0.005 and P<0.001, respectively). Magnesium (1.6 mmol/L
      vs 1.8 mmol/L) and zinc levels (14.9 micromol/L vs 19.2 micromol/L) were
      significantly decreased, whereas copper levels (19.3 micromol/L vs 17.9
      micromol/L) were increased in alcoholics (P=0.042, P<0.001 and P=0.003,
      respectively). Echocardiographic examination showed a significant decrease in
      mitral and tricuspid ratio of peak early and atrial flow velocity (E/A ratio) in
      alcoholics. CONCLUSION: Decrease in mitral and tricuspid E/A ratios accompanied
      with low levels of magnesium and zinc, and increased levels of copper indicate
      that alcoholics already have heart muscle disease even chronic alcohol exposure.

PMID- 15849845
TI  - Metoclopramide improves gastric but not gallbladder emptying in cardiac surgery
      patients with early intragastric enteral feeding: randomized controlled trial.
AB  - AIM: To evaluate the effect of metoclopramide on gastric emptying in coronary
      artery bypass graft (CABG) surgery patients with early enteral nutrition and to
      evaluate the effect of metoclopramide on motility of the gallbladder in these
      patients. METHODS: A prospective, randomized, placebo-controlled, double-blind
      study of 40 patients treated at cardiosurgical intensive care unit after CABG
      surgery. The patients were divided into two groups: metoclopramide group (20
      patients; age 60-/+9 years; 85% male), and control group (20 patients; age 59-/+8
      years; 70% male). In both groups, enteral feeding with isoosmotic enteral formula
      was initiated by nasogastric tube 18 hours after surgery. After 6 hours, feeding
      was stopped, and paracetamol solution (1,000 mg) and 10 mg of metoclopramide IV
      or 2 ml of saline IV were concurrently administered. Blood samples were obtained
      15 (t(+15)), 30 (t(+30)), 60 (t(+60)), and 120 (t(+120)) minutes after the
      administration of paracetamol. Paracetamol absorption was assessed from the
      plasma paracetamol concentration and the area under the curve (AUC) from 0 to 120
      minutes. Sonographic measurement of gallbladder ejection fraction was also
      performed 15 (t(+15)), 30 (t(+30)), 60 (t(+60)), and 120 (t(+120)) minutes after
      the administration of paracetamol. RESULTS: The plasma paracetamol concentrations
      15, 30, 60, and 120 minutes after the administration of paracetamol were
      significantly higher in metoclopramide group than in control group: (t(+15)) 5.4
      /+2.7 vs 3.3-/+2.5 (Mann-Whitney U test; P=0.017); (t(+30)) 6.7-/+2.4 vs 3.7
      /+2.0 (P=0.006); (t(+60)) 7.7-/+2.5 vs 5.1-/+3.2 (P=0.008); (t(+120)) 8.5-/+2.2
      vs 5.2-/+2.8 (P=0.005). The AUC value was 34% larger in the metoclopramide group
      vs control group (574-/+296 vs 429-/+309; P=0.027). There were no significant
      differences in gallbladder ejection fraction between groups (group metoclopramide
      vs control group: (t(0)-t(+15)) -2% vs -2%; (t(+15)-t(+30)) 1% vs 4%; (t(+30)
      t(+60)) 0% vs -1%; (t(+60)-t(+120)) 1% vs 3%; P=NS). CONCLUSIONS: In CABG surgery
      patients with early enteral feeding, a single dose of intravenous metoclopramide
      effectively improves gastric emptying, but does not have any prokinetic effect on
      gallbladder motility.

PMID- 15849846
TI  - Correlation of perforating vein incompetence with extent of great saphenous
      insufficiency: cross sectional study.
AB  - AIM: To explore the correlation between perforating vein incompetence and the
      extent of great saphenous vein insufficiency according to Hach. METHODS: Duplex
      ultrasound was used to determine the number of incompetent perforators and
      diameter of perforating veins, and the level of great saphenous vein reflux and
      the presence or absence of deep reflux in 118 lower limbs (59 patients). There
      were 19 limbs with no clinical evidence of venous disease (CEAP - clinical,
      etiological, anatomical, pathological grade 0), 16 limbs with telangiectasias
      only (CEAP grade 1), 36 limbs with varicose veins (CEAP 2), 26 limbs with edema
      (CEAP 3), and 21 limb affected with lipodermatosclerosis but not ulcer (CEAP 4).
      RESULTS: Both the number of incompetent perforators and the average diameter of
      duplex detectable perforators per limb correlated significantly with the extent
      of great saphenous vein insufficiency (Pearson correlation coefficients were 0.55
      and 0.44, respectively; P<0.001 for both). The number of incompetent perforators
      and the average diameter of perforators per limb were significantly higher with
      the deteriorating CEAP grade (Kruskal-Wallis H test; P<0.001). The mean number of
      incompetent perforators per limb did not differ significantly in the absence or
      presence of deep reflux (0.8-/+1.26 vs 1.3-/+1.6, t test, P=0.172), the average
      diameter of perforators per limb was higher in the presence of deep reflux (2.4
      /+2 mm vs 3.7-/+1.1 mm, t test, P=0.023). CONCLUSION: The extent of great
      saphenous vein insufficiency correlated with an increase in the number and the
      diameter of perforators. The perforators' association with deep venous reflux was
      much poorer. Clinical presentation worsened with the deteriorating duplex signs
      of perforators' incompetence.

PMID- 15849847
TI  - Gender differences in knee kinematics and its possible consequences.
AB  - AIM: To analyze anatomic and kinematic characteristics of male and female knees
      in the sagittal plane. METHODS: Ten healthy male and 10 healthy female
      participants performed extension of their right lower leg in non-weight bearing
      and weight bearing conditions. The centers of knee joint motion were obtained by
      videographic motion analysis, and radii of condylar curves were calculated from
      digitalized X-ray scan. The Knee Roll software was made for this purpose.
      RESULTS: The extension of the knee in non-weight loaded and weight loaded
      conditions is a combination of rolling and sliding joint surface motion with 6:5
      ratio, in both genders. During the last 20 degrees of the extension of weight
      loaded male knee, rolling/sliding ratio changed to 8:1 (P<0.05). Average radii of
      condylar curves were between 4.5 and 1.7 cm medially, and between 3.2 and 1.8 cm
      laterally, for 0 degrees and 90 degrees flexion contact point, respectively.
      Gender differences in the radii of condylar curves, after the adjusting to body
      height were insignificant. CONCLUSION: A higher proportion of joint surface
      sliding with consecutive anterior tibial displacement in women indicates more
      strain during knee extension, potentially making the female anterior cruciate
      ligament tend and susceptible to injury. The gender differences in the knee
      kinematics are probably the consequence of different soft tissue structure or its
      activity, because no difference in the sagittal shape of femoral condyles was
      noted.

PMID- 15849848
TI  - Stability of Endler cementless polyethylene acetabular cup: long-term follow-up.
AB  - AIM: To investigate the possible influence of demographic and biomechanical
      factors on stability of the Endler cementless polyethylene acetabular cup.
      METHODS: This was a retrospective cohort study. Seventy-two patients (25 men, 47
      women) bearing 82 Endler prostheses, all of which were implanted by the same
      surgeon in the period between 1985 and 1991, were invited for a control visit
      (final visit) in July 2003. During time between the surgery and the final visit,
      the patients were followed-up regularly and assessed for clinical and
      radiological signs of the Endler cup instability based on Krugluger and Eyb's
      criteria. The Kaplan-Meier product limit method and the Cox proportional hazard
      regression analysis were used to investigate the survival of the cup (time since
      implantation till the diagnosis of instability) and possible influence of the
      following factors: age and body mass index at the time of surgery, gender,
      achieved acetabular cup inclination angle, and acetabuloplasty and/or trochanter
      osteotomy performed during surgery. RESULTS: The median follow-up period was 15
      years (range 5-18). Cumulative survival rates at 5, 10, 15, and 18 years were
      97.6% (95% CI=94.2-100), 74.4% (95% CI=64.9-83.8), 53.7% (95% CI=42.9-64.5), and
      44.5% (95% CI=29.5-59.6), respectively. The median survival time was 18 years (13
      18). Unsatisfactory acetabular cup inclination angle (<41 or >49 degrees) was a
      negative predictor of the cup survival (P=0.026), whereas the interaction between
      the inclination angle and an unsatisfactory body mass index (>upper normal limit)
      was of borderline significance (P=0.056). The analyzed demographic and
      biomechanical factors apparently explained only a minor part of the survival
      variability (R(2)=0.173). CONCLUSION: This study further documents the impact of
      the acetabular cup inclination angle achieved at surgery on the Endler cup
      survival. However, it also suggests that the prosthesis survival might be
      influenced by other, non-biomechanical factors.

PMID- 15849849
TI  - Increased Th1 and Th2 immune reactivity with relative Th2 dominance in patients
      with acute exacerbation of schizophrenia.
AB  - AIM: To determine concentration of T helper (Th(1)) cytokines and Th(2) cytokines
      in patients with acute exacerbation of schizophrenia and compare the cytokine
      profiles between subtypes of schizophrenia. METHOD: One hundred inpatients with
      acute exacerbation of schizophrenia and 34 matched healthy subjects from the same
      population without psychiatric history were included in the study. According to
      predominant symptom complexes the patients were divided into three subgroups:
      hallucinations and delusions (n=36); disorganized behavior (n=33), and primary,
      enduring negative or deficit symptoms (n=31). In vitro IFN-gamma and IL-4
      secretion by peripheral blood mononuclear cells after stimulation with ionomycin
      and phorbol 12 myristate 13 acetate was measured by enzyme-linked immunosorbent
      assay (ELISA) tests. RESULTS: Significant increase in in vitro secretion of IFN
      gamma (21,505 vs 14,915 pg/mL; P=0.037; independent samples t test) and IL-4 (32
      vs 15 pg/mL; P<0.001) with a shift to the Th(2) (1,022 vs 1,432 pg/mL; P=0.005)
      immune response was observed in patients with schizophrenia compared to healthy
      controls. We found pronounced effects of age and age at first hospitalisation on
      the Th(1)/Th(2) immune balance (R(2)=0.068; P=0.037). There were no significant
      differences in in vitro secretion of IFN-gamma (P=0.734; one-way analysis of
      variance), IL-4 (P=0.485) and IFN-gamma/IL-4 ratio (P=0.293) between the
      subgroups of patients with schizophrenia. CONCLUSION: Our findings indicate a
      simultaneous increase of in vitro reactivity of both Th(1) and Th(2) arm of cell
      mediated immunity, with a relative predominance of Th(2) immunity in patients
      with acute exacerbation of schizophrenia.

PMID- 15849850
TI  - Psychosomatic and depressive symptoms in civilians, refugees, and soldiers: 1993
      2004 longitudinal study in Croatia.
AB  - AIM: To evaluate psychosomatic complaints and depressive symptoms among
      civilians, refugees, and soldiers in the war and post-war period in Croatia.
      METHOD: The design of the study was longitudinal, including four repeated
      assessments during the war and post-war period (1993, 1995, 2000, and 2004). The
      baseline assessment included 480 male participants who were asked to fill out the
      questionnaires about demographic data, psychosomatic complaints, and depressive
      symptoms. The final sample included 128 civilians, 88 refugees, and 70 soldiers,
      who were interviewed at all assessment time points. RESULTS: Levels of
      psychosomatic and depressive symptoms changed with time. Refugees showed the
      highest level of depressive symptoms in general (F=4.17, P=0.016). Psychosomatic
      complaints were dominant in soldiers and refugees at all assessment time points
      (F=210.30, P<0.001). Soldiers showed a significant increase in psychosomatic
      complaints with time, whereas refugees showed a decrease. Contrary to these
      findings, civilians showed relatively low level of psychosomatic complaints and
      did not show any significant changes with time. CONCLUSION: It seems that for
      refugees and soldiers, prolonged stressful situation has long-term health
      implications primary related to the psychosomatic complaints.

PMID- 15849851
TI  - Memory function in patients with obsessive compulsive disorder and the problem of
      confidence in their memories: a clinical study.
AB  - AIM: To examine obsessive-compulsive patients for memory of obsessive-compulsive
      relevant material and confidence in their memory. METHODS: Memory function was
      examined by a recognition task using neutral and obsessive-compulsive relevant
      sentences in 32 patients with obsessive-compulsive disorder and 31 control
      subjects. We also investigated the participants' confidence in the accuracy of
      their recognition. The severity of obsessive-compulsive disorder was evaluated by
      using the Yale-Brown Obsessive Compulsive Scale. The Maudsley Obsessive
      Compulsive Questionnaire, the Hamilton Depression Rating Scale, and the State
      Trait Anxiety Inventory were also administered to the two groups. RESULTS:
      Whereas obsessive-compulsive disorder patients were not significantly different
      from control subjects on measures of recognition memory for both obsessive
      compulsive relevant and neutral material, they were significantly less confident
      in the memory for obsessive-compulsive relevant and neutral sentences. Also, the
      State-Trait Anxiety Inventory (STAI) scores were negatively correlated with the
      recognition performance of obsessive-compulsive disorder relevant sentences and
      the levels of confidence in memory in the obsessive-compulsive disorder group.
      The obsessive-compulsive patients with checking compulsions were not different
      from non-checking obsessive-compulsive patients. CONCLUSION: Our results suggest
      that obsessive-compulsive patients experience difficulties in confidence in their
      memory, possibly related to anxiety rather than primary memory deficits.

PMID- 15849852
TI  - Gender differences in suicide attempters in Hungary: retrospective
      epidemiological study.
AB  - AIM: To determine gender differences in suicidal behavior and investigate the
      factors associated with suicide attempts. METHODS: In the framework of the
      WHO/Euro Multicenter Study on Suicidal Behavior, 1,158 suicide attempts have been
      registered and analyzed retrospectively in Pecs center, Hungary. Descriptive
      statistics and logistic regression analysis were performed to compare the
      characteristics of male and female suicide attempters. RESULTS: A "typical"
      female suicide attempter could be characterized as follows: retired or
      economically inactive (OR=2.38), widowed (OR=6.55), divorced (OR=1.64), or with
      depression in her personal history (OR=1.27). Female attempters were mainly
      repeaters, using the method of self-poisoning, mostly with benzodiazepines. Among
      men, unemployment, living alone, never having been married, and problems with
      addiction were the main risk factors, while violent methods characterized the
      typical attempt In the cases of self-poisoning, men were more likely to take
      meprobamate or carbamazepine. CONCLUSION: Significant differences were found in
      the risk factors for suicide attempts between men and women. Since suicide is a
      multi-causal phenomenon, its therapy and prevention should be complex and gender
      differences should be taken into consideration while building up our helping
      strategies.

PMID- 15849853
TI  - Anthropometric and cardiopulmonary parameters in Bulgarian and Romany children:
      cross-sectional study.
AB  - AIM: To examine anthropometric parameters and cardiopulmonary function in
      Bulgarian and Romany children. METHODS: Two hundred and ten healthy children (153
      Bulgarian and 57 Romany) of similar age (10.5-/+0.5 years, mean-/+standard
      deviation) underwent an anthropometric and pulmonary function assessment and
      performed an exercise test on a treadmill, using the modified Balke protocol.
      RESULTS: Bulgarian children were significantly taller (145-/+7 vs 142-/+7 cm) and
      heavier (39-/+9 vs 35-/+8 kg) than Romany children. They also had more body fat
      (20.5-/+8.1% vs 17.8-/+7.6% in Romanies). In a subset of the whole sample, it was
      established that Bulgarian children had significantly higher birth weight in
      comparison with Romanies (3,358-/+513 vs 3,095-/+435 g; P=0.006). Mean absolute
      values of vital capacity (VC), forced expiratory volume in 1 s (FEV(1)) and
      transfer factor (T(L,CO)) were lower for Romany than for Bulgarian children,
      7.8%, 7.3%, and 10.2%, respectively. The data from the incremental treadmill test
      showed that peak oxygen uptake (VO(2)peak) did not differ significantly between
      the two ethnic groups (1,341-/+293 vs 1,260-/+280 mL/min). The level of physical
      exertion was almost the same in the studied groups (respiratory exchange ratio
      (RER)=1.08-/+0.08 vs 1.08-/+0.06), but the perception of exertion was higher in
      Bulgarian children (Borg score=4.9-/+1.5 vs 3.2-/+1.5; P<0.001). CONCLUSIONS:
      There are significant differences between Bulgarian and Romany children with
      regard to anthropometric parameters, including stature, lung function indices,
      and perception of exertion.

PMID- 15849854
TI  - Genetics, obesity, and environmental risk factors associated with type 2
      diabetes.
AB  - AIM: To determine the association between consanguineous marriages, obesity, and
      environmental risk factors associated with type 2 diabetes, in the adult Qatari
      population. METHODS: The case-control study was carried out among diabetic
      patients and healthy subjects at the Primary Healthcare Clinics (PHCs) and the
      survey was conducted from February to November 2003. The study included 338 cases
      (with diabetes) and 338 controls (without diabetes). Face-to-face interviews were
      based on a questionnaire that included variables such as age, gender,
      socioeconomic status, parity, income level, cigarette smoking, physical activity,
      body mass index (BMI), obesity, and lifestyle. Their health status was assessed
      by medical conditions, family history, physical examination, blood pressure,
      blood glucose, blood count, lipid profile, cholesterol total, HDL, LDL, and
      triglycerides analysis. RESULTS: The mean age (in years-/+standard deviation) of
      cases versus controls was 45.5-/+8.9 vs 42.4-/+8.0, P<0.001. The study revealed
      that there were statistically significant differences between diabetic and
      control subjects with respect to body mass index, low educational level,
      consanguineous marriage, and number of children (P<0.001). The obesity was
      considerably more frequent among diabetes subjects (P<0.001). Self reported
      family history (in first degree relatives) of diabetes (62.1% vs 44.4%, OR=2.06,
      95% confidence interval (CI)=1.49-2.83) P<0.001) was prominent among diabetic
      subjects. The diabetes was significantly common among the consanguineous
      marriages of the first degree relatives compared with the control group (33.1%
      vs. 24.6%, OR=1.59, 95% CI=1.11-2.29), P=0.008). Systolic blood pressure
      (P=0.023) and glucose fasting (P<0.001) levels were significantly higher in
      diabetic patients than in control subjects. The logistic regression model showed
      that smoking (OR=2.42 95% CI=1.66-3.54, P<0.0001); degree of consanguinity
      (OR=1.38 95% CI=1.13-1.69, P=0.002), BMI (OR=1.41 95% CI=1.12-1.76), P=0.003),
      level of education (OR=1.23 95% CI=1.04-1.45, P=0.017), number of children
      (OR=1.34 95% CI=1.02-1.77, P=0.037), and systolic blood pressure (OR=1.01 95%
      CI=1.00-1.02, P=0.044) were considered as associated risk factors for diabetes.
      CONCLUSION: The present study revealed that obesity, consanguinity, blood
      pressure, total cholesterol, HDL-cholesterol, and triglycerides were more
      prevalent in diabetic patients. The characterization of these factors will
      contribute to defining more effective and specific strategies to screen for and
      control diabetes and cardiovascular disease in a developing country.

PMID- 15849855
TI  - Do patients with different psychiatric diagnoses require different strategies for
      certifying sick leave? - first indications from a prospective study.
AB  - AIM: To analyze the relationship between duration of prior certified sick leave
      and the course of symptom severity in a prospective study. METHODS: The severity
      of psychiatric symptoms was assessed in 109 patients of a
      psychosomatic/psychotherapeutic polyclinic. Using a basic patient documentation
      and the Symptom-Check-List SCL-90-R, sociodemographic information, diagnosis,
      symptom duration, and duration of sick leave were assessed at admission and four
      to six months later. Intra-individual difference scores were calculated for each
      patient to assess changes in the severity of psychiatric symptoms. RESULTS: A
      highly significant interaction between the course of symptom severity, duration
      of prior sick leave, and diagnostic group was found with two-factorial analysis
      of variance (F=2.888; P>/=0.01). At the second assessment, patients with anxiety
      disorders and longer sick leave showed a higher degree of deterioration in
      symptoms compared with anxiety patients with shorter or no prior sick leave. The
      patients with depression disorders and long certified sick leave achieved a
      higher degree of improvement in symptoms compared with depressive patients with
      shorter or no prior certified sick leave. CONCLUSION: Different diagnostic groups
      of psychiatric patients require different strategies for certifying sick leave.

PMID- 15849856
TI  - Q fever epidemic among employees in a factory in the suburb of Zadar, Croatia.
AB  - AIM: To examine the role of wind in the spread of Q fever (Coxiella burnetii)
      from the source of infection (sheep on the pastures) to the factory where there
      was an outbreak of Q fever among the employees. METHODS: We performed clinical
      (fever, coughing, myalgias, arthralgias), laboratory (complete blood test,
      aminotransferases, antibodies to Coxiella burnetii), radiographic (chest X-ray),
      and epidemiological (questionnaire) analysis on 47 of 110 employees of the plant
      in a suburb of Zadar. Sera of 182 sheep were tested for antibody to C. burnetii
      by complement fixation reaction. RESULTS: During the first half of March 2004, 14
      of 110 employees of a factory in a suburb of Zadar were diagnosed with Q fever on
      the basis of clinical and laboratory findings. In three sections of the plant,
      directly exposed to the north wind, a diagnosis of Q fever was confirmed in 14 of
      110 employees by clinical, laboratory, and X-ray analysis, whereas there were no
      sick employees in the other four sections. North of the plant there were pastures
      where many flocks of sheep grazed. Antibodies to C. burnetii were found in 20 out
      of 182 sheep sera. Employees who were exposed to the north wind, had a
      significantly higher possibility of acquiring Q fever than did those working in
      sections protected from the wind. CONCLUSION: North wind (bura) containing the
      aerosolized C. burnetii likely influenced the Q fever outbreak in persons far
      from the source of the infection.

PMID- 15849857
TI  - Attitudes of school environment towards integration of HIV-positive pupils into
      regular classes and knowledge about HIV/AIDS: cross-sectional study.
AB  - AIM: To estimate the attitudes of teachers, parents, and pupils in primary
      schools towards the integration of HIV-positive pupils into regular schools, and
      their knowledge about HIV/AIDS. METHODS: Teachers (n=64), seventh and eight grade
      pupils (n=108), and their parents (n=124) from a big city and a small town in
      Croatia were examined by two specially designed instruments which measured their
      attitudes towards the integration of pupils with HIV/AIDS and knowledge about
      HIV/AIDS. RESULTS: All three populations showed positive attitudes towards the
      integration of children with HIV/AIDS into regular schools. A group of parents
      had lower attitude score (mean-/+standard deviation, 3.1-/+0.6) compared with
      teachers or pupils (3.5-/+0.4 and 3.4-/+0.4 respectively, P<0.001, ANOVA, and
      post hoc Tukey test). Knowledge about HIV/AIDS was high in all three groups.
      Pupils scored lower (8.2-/+4.1 out of maximum 15) than their teachers or parents
      (11.2-/+3.8 and 10.3-/+3.5 respectively, P<0.001). In all three subsamples,
      groups with higher level of education had more positive attitudes towards the
      integration of children with HIV/AIDS into regular schools as well as higher
      knowledge scores. No significant correlation was found between participants'
      attitudes and knowledge. CONCLUSION: School environment - teachers, pupils,
      parents - had generally positive attitudes towards the integration of HIV
      positive pupils and high level of knowledge about HIV/AIDS. Generally, parents
      showed less favorable attitudes than teachers and pupils and this may be a
      possible obstacle to the integration of HIV positive students into regular
      schools. There is obviously a need for a coordinated public intervention aimed at
      informing the public about HIV/AIDS.

PMID- 15849858
TI  - Guide for peer reviewers of scientific articles in the Croatian Medical Journal.
AB  - Despite its shortcomings, peer review is still the best tool of scientific
      publishing. It brings benefits not only to the journal and its authors, but to
      the peer reviewers: they are privileged to have an insight into the latest
      research and still unpublished results in their scientific field. Reviewers also
      build up their ability to critically assess scientific papers, which may be
      useful in their own professional work and development. We wrote these brief
      guidelines to help the reviewers for the Croatian Medical Journal learn about the
      specificities of the journal and editor's expectations from their partnership
      with peer reviewers. The guidelines were created primarily for new reviewers, but
      they may be useful as a refresher text for experienced reviewers.

PMID- 15849859
TI  - The perils of the single criterion of success.

PMID- 15849860
TI  - Healing after harm.

PMID- 15849861
TI  - Don't dismiss astrobiology.

PMID- 15849862
TI  - Don't dismiss astrobiology. Response.

PMID- 15849863
TI  - Perspectives. It's not your father's DM... it's your grandfather's.

PMID- 15849864
TI  - [Bifocal atypical rolandic epilepsy with speech dyspraxia].
AB  - Clinical and neurophysiological analysis of a case of a 7 year old patient with
      typical benign partial seizures with rolandic spikes and speech disorder,
      differing from those in Landau-Kleffner syndrome and in typical benign partial
      epilepsy of childhood presenting as speech dyspraxia. Two independent foci (in
      the premotor cortex of the left front lobe (dominant hemisphere) and in the
      temporal lobe of the right hemisphere were found. Significant clinical
      improvement and electrographical positive effect in EEG were achiered after
      prednisolone and sodium valproate treatment.

PMID- 15849865
TI  - [The addiction of ephedrine like psychostimulators and use of nimotop for its
      correction].
AB  - Twenty six patients, used home-made ephedrine like psychostimulators were
      examined. Nervous system pathology in these cases was characterized by short
      (several months) period of the pathological process formation, young patient's
      age, absence of family psychiatric history, pronounced systemic and multilevel
      affection of the organism, severity of psychic defects and patients disability.
      Electrophysiological study revealed essential changes of neurodynamics
      manifesting with insufficiency of non-specific activating brain system,
      diencephalic stem structure dysfunction, deep structure irritation that might
      correspond to clinical picture of multisystem CNS lesions. An involvement of
      limbic reticular structures in pathological process on the background of
      neurophysiological immaturity was detected as well. In patients disorders of
      brain homeostatic mechanisms and cognitive functions were also found. Deprivation
      of reactivity of upper-segmental autonomic system regulation can determine
      rigidity and pathological adaptation of such patients. Insufficiency of
      activating systems of reticular formation, arrhythmia, disturbances of cognitive
      functions and cerebral homeostasis dictate a need for nootropics prescription for
      these patients. Clinical experience justifies including drug nimotop in complex
      treatment and rehabilitation schemes.

PMID- 15849866
TI  - [Influence of L-DOPA on rat brain depending on individual behavioral features].
AB  - To cause brain dopaminergic hyperactivity in rats, L-DOPA was injected in August
      and Wistar rats with different basic stress reactivity and motor activity in open
      field ecperiments during 14 days. L-DOPA was used in the form of the drug madopar
      in dosage of 25,5 mg/kg of body mass daily. The indices of activity of metabolism
      enzymes, neuromediators and proteins: aminopeptidase, glutamatedehydrogenase,
      monoaminoxidase (substrate triptamine) and acetylcholinesterase were studied in
      sensomotor cortex, caudate nucleus, nucleus accumbens and hippocampus region. The
      intra- and between-line features of L-DOPA influence on rat brain have been
      found, being mostly pronounced in the animals with low motor activity. In these
      rats, changes were observed in all structures and for all enzymes, but in the
      group with high activity they concerned only GDH in caudate nucleus and nucleus
      accumbens. Hippocampus was the structure reacting to L-DOPA most actively as
      shoun by cytochemical indices, with reactions relating mainly to serotonergic
      system in August rats and to acetylcholinergic and glutamatergic systems in
      Wistar rats. The results demonstrate an essential role of genetically determined
      reactivity and motor activity in individual prognosis of resistance to stress and
      extreme situations.

PMID- 15849867
TI  - [Movalis in treatment of painful shoulder syndrome in poststroke patients].

PMID- 15849868
TI  - Detection of sexually transmitted pathogens in patients with hematospermia.
AB  - BACKGROUND: Although the current literature attributes most cases of
      hematospermia to an infectious agent, identification of the specific pathogens
      involved has been limited. OBJECTIVES: To determine the prevalence of different
      pathogens in patients presenting with hematospermia to our sexually transmitted
      disease clinic. METHODS: Between January 1999 and January 2000, 16 patients
      presented to our STD clinic with hematospermia after other noninfectious
      pathologies had been excluded by a referring physician. After obtaining informed
      consent, subjects completed a questionnaire addressing symptoms and sexual
      behavior. First-void urine samples, as well as genitourinary and serum specimens
      were tested for Chlamydia trachomatis, Ureaplasma urealyticum and herpes simplex
      virus. Standard bacterial cultures were also performed. RESULTS: Laboratory
      testing detected a pathogen in 12 of the 16 males presenting with hematospermia.
      The sexually transmitted pathogens detected were herpes simplex virus in 5
      patients (42%), Chlamydia trachomatis in 4 (33%), Enterococcus fecalis in 2
      (17%), and Ureaplasma urealyticum in 1 (8%). In all cases in which a pathogen was
      identified, the appropriate antimicrobial agent was administered. Symptoms
      resolved for each patient following antimicrobial therapy. During a 1 year follow
      up, all 12 patients remained free of disease. CONCLUSIONS: Recent advances in
      microbiologic diagnostic techniques have facilitated the detection of pathogens
      in patients with hematospermia, thereby enhancing the efficacy of treatment.

PMID- 15849870
TI  - Evaluation of French Guiana traditional antimalarial remedies.
AB  - In order to evaluate the antimalarial potential of traditional remedies used in
      French Guiana, 35 remedies were prepared in their traditional form and screened
      for blood schizonticidal activity in vitro on Plasmodium falciparum chloroquine
      re4sistant strain (W2). Some of these extracts were screened in vivo against
      Plasmodium yoelii rodent malaria. Ferriprotoporphyrin inhibition test was also
      performed. Four remedies, widely used among the population as preventives, were
      able to inhibit more than 50% of the parasite growth in vivo at around 100 mg/kg:
      Irlbachia alata (Gentiananceae), Picrolemma pseudocoffea (Simaroubaceae), Quassia
      amara (Simaroubaceae), Tinospora crispa (Menispermaceae) and Zanthoxylum
      rhoifolium (Rutaceae). Five remedies displayed an IC50 in vitro < 10 microg/ml:
      Picrolemma pseudocoffea, Pseudoxandra cuspidata (Annonaceae) and Quassia amara
      leaves and stem, together with a multi-ingredient recipe. Two remedies were more
      active than a Cinchona preparation on the ferriprotoporphyrin inhibition test:
      Picrolemma pseudocoffea and Quassia amara. We also showed that a traditional
      preventive remedy, made from Geissospermum argenteum bark macerated in rum, was
      able to impair the intrahepatic cycle of the parasite. For the first time,
      traditional remedies from French Guiana have been directly tested on malarial
      pharmacological assays and some have been shown to be active.

PMID- 15849869
TI  - [In vitro susceptibilites to levofloxacin and various antibacterial agents of
      11,475 clinical isolates obtained from 52 centers in 2002].
AB  - The susceptibilities of bacteria to fluoroquinolones (FQs), especially
      levofloxacin, and other antimicrobial agents were investigated using 11,475
      clinical isolates collected in Japan during 2002. Methicillin susceptible
      staphylococci, Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella
      catarrhalis, the family of Enterobactericeae, Haemophilus influenzae and
      Acinetobacter spp. exhibited stable and high susceptibilities to FQs. The rate of
      FQs-resistant MRSA was 80 approximately 90%, being markedly higher than that of
      FQs-resistant MSSA. The FQs-resistance rate of MRCNS was also higher than that of
      MSCNS, however, it was lower than that of MRSA. No FQs-resistant clinical
      isolates of Salmonella spp. were detected in any of the surveys. Thirteen of
      Escherichai coli 696 isolates, 8 of Klebsiella pneumoniae 630 isolates and 33 of
      Proteus mirabilis 373 isolates produced extended-spectrum beta-lactamase (ESBL),
      furthermore 6 of 13 in E. coli, 1 of 8 in K. pneumoniae and 14 of 31 ESBL
      producing isolates, and in P. mirabilis were FQs resistant. Attention should be
      focused in the future on the emergence of ESBL in relation to FQs resistance. The
      rate of FQs-resistant P. aeruginosa isolated from urinary tract infection (UTI)
      was 40 approximately 60%, while 15 approximately 25% of isolates from respiratory
      tract infection (RTI) were resistant. IMP-1 type metallo beta-lactamase producing
      organisms were found in 49 of P. aeruginosa 1,095 isolates, 7 of S. marcescens
      586 isolates and 4 of Acinetobacter spp. 474 isolates, respectively. Glycopeptide
      resistant enterococci or S. aureus was not found.

PMID- 15849872
TI  - A novel caspase-7 specific monoclonal antibody.

PMID- 15849871
TI  - Biological importance of the two Toll-like receptors, TLR2 and TLR4, in
      macrophage response to infection with Candida albicans.
AB  - The aim of this study was to assess the role of TLR2, TLR4 and MyD88 accessory
      molecule in the effector and secretory response of macrophages to viable
      microbial agents. Using TLR-deleted macrophage cell lines generated from the bone
      marrow of genetically engineered mice (TLR4 gene-deficient, MyD88- and TLR2
      knockout mice) and wild-type control mice, we found that TLR2-deleted macrophages
      exhibit increased ability to contain Candida albicans infection compared to
      TLR2+/+ counterpart. In contrast, both MyD88-/- and TLR4-/- macrophages retain
      levels of functional activity comparable to that of the respective wild-type
      MyD88+/+ and TLR4+/+ controls. The difference in anticandidal effector functions
      observed between TLR2-/- and TLR2+/+ macrophages is abrogated upon opsonization
      of the fungal target and interestingly is not observed when using other microbial
      targets, such as Streptococcus pneumoniae and Helicobacter pylori. When tested
      for secretory response to C. albicans, TLR2-deleted macrophages show a pattern of
      cytokine production similar to that of TLR2+/+ controls. Finally, flow cytometry
      analysis reveals that TLR2-deleted macrophages express only TLR4, while, as
      expected, TLR2+/+ macrophages are both TLR2 and TLR4 positive; in no cases,
      modulation of such markers occurs in macrophages exposed to C. albicans
      infection. In conclusion, these data indicate that TLR2 and TLR4 have different
      biological relevance, in which TLR2 but not TLR4, is involved in the
      accomplishment of macrophage-mediated anticandidal activity, while the secretory
      response to C. albicans appears to be TLR4 but not TLR2-dependent.

PMID- 15849873
TI  - Sensed presence and mystical experiences are predicted by suggestibility, not by
      the application of transcranial weak complex magnetic fields.
AB  - Transcranial magnetic stimulation (TMS) with weak (micro Tesla) complex waveform
      fields have been claimed to evoke the sensed presence of a sentient being in up
      to 80% in the general population. These findings have had a questionable
      neurophysiological foundation as the fields are approximately six orders of
      magnitude weaker than ordinary TMS fields. Also, no independent replication has
      been reported. To replicate and extend previous findings, we performed a double
      blind experiment (N=89), with a sham-field control group. Personality
      characteristics indicating suggestibility (absorption, signs of abnormal temporal
      lobe activity, and a "new age"-lifestyle orientation) were used as predictors.
      Sensed presence, mystical, and other somatosensory experiences previously
      reported from the magnetic field stimulation were outcome measures. We found no
      evidence for any effects of the magnetic fields, neither in the entire group, nor
      in individuals high in suggestibility. Because the personality characteristics
      significantly predicted outcomes, suggestibility may account for previously
      reported effects. Our results strongly question the earlier claims of
      experiential effects of weak magnetic fields.

PMID- 15849874
TI  - Meeting report: Part II. Notes from the Twentieth Annual Clinical Virology
      Symposium.

PMID- 15849875
TI  - Effects of ethanolic extract of Iris germanica on lipid profile of rats fed on a
      high-fat diet.
AB  - Ethanolic extract of Iris germanica rhizomes was investigated for hypolipidemic
      activity. I. germanica belong to the family Irdaceae and has been used to treat
      liver and spleen ailments in traditional system of medicine. Two groups of Wistar
      rats were fed with high-fat diet and ethanolic extract of I. germanica were
      administered orally in one group of rats, while other received saline for 10
      weeks. Complete lipid profiles of experimental animals were determined by
      assessing serum levels of total lipids, triglycerides, cholesterol, high-density
      lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol. Results
      indicate that ethanolic extract of I. germanica significantly lowered the lipid
      components especially, the cholesterol and triglycerides.

PMID- 15849876
TI  - Rapid increase in numbers of Staphylococcus epidermidis strains with reduced
      susceptibility to teicoplanin in Greece.

PMID- 15849877
TI  - Evaluation of Alstonia scholaris leaves for broncho-vasodilatory activity.
AB  - The present study demonstrates that the ethanol extract of Alstonia scholaris
      (Apocynaceae) leaves induced pronounced bronchodilatory activity in anaesthetized
      rats with the probable involvement of prostaglandins. However, in vitro
      preparations of guinea-pig trachea did not confirm this property, indicating that
      bronchodilation is not due to the direct tracheal smooth muscle relaxation. The
      vasodilatory activity of the extract was independent of adrenergic or muscarinic
      receptors or prostaglandins but was mainly via endothelial-derived relaxing
      factor, nitric oxide. The extract inhibited the spontaneous movements of rabbit
      jejunum and contractile effects of acetylcholine and histamine on guinea-pig
      ileum. Additionally, the extract caused marked reduction of barium chloride-,
      potassium chloride- and calcium chloride-induced contraction on guinea-pig ileum
      and pulmonary artery, implying a direct interference of plant extract with the
      influx of calcium ions into cells. However, the extract has no detectable effect
      on mobilization of intracellular calcium. These results coupled with the in vivo
      effects of ethanol extract reveal that the Alstonia scholaris leaves possess
      broncho-vasodilatory activity mediated presumably by prostaglandins, calcium
      antagonism and endothelium-derived relaxing factor(s).

PMID- 15849879
TI  - Proceedings of a leadership retreat conducted by ASHP Foundation and the John W.
      Webb visiting professor program.

PMID- 15849878
TI  - Will there be a pharmacy leadership crises? An ASHP Foundation Scholar-in
      residence report.
AB  - PURPOSE: Health-system pharmacy directors, managers, practitioners, students, and
      employers were surveyed to assess the situation of current and future leaders in
      pharmacy and generate recommendations for preventing shortages. METHODS: Online
      surveys were sent to pharmacy directors, pharmacy middle managers, current
      pharmacy practitioners pharmacy students, and employers recruiting for management
      positions using ASHP's membership and CareerPharm databases. Directors, managers,
      and practitioners were asked about their job satisfaction and future plans. The
      trends in demographics and attitudes toward the balance between family and work
      were assessed among directors, managers, practitioners, and students. Employers
      were asked about their perceived ease of filling managerial positions. RESULTS:
      While most pharmacy directors and middle managers were satisfied with their
      current positions, 80% of directors and 77% of middle managers anticipated
      leaving their jobs in the next decade. Men comprised 72% of directors, 50% of
      middle managers, 62% of practitioners, and 21% of pharmacy students. The majority
      of pharmacy students and practitioners reported being married to a working spouse
      and having children and expressed a desire to balance their personal life with
      their career. The top reasons cited by students and practitioners for not seeking
      leadership positions were having to give up clinical practice and competing
      responsibilities. More than half of employers felt it was more difficult to
      recruit managers now than it was three years ago. CONCLUSION: A significant gap
      in pharmacy leadership in the next 5-10 years is expected, as well as a shift in
      work force composition and attitude. Mentoring and residencies are important
      methods of fostering new leaders in the profession.

PMID- 15849880
TI  - Continuing bonds in bereavement: an attachment theory based perspective.
AB  - An attachment theory based perspective on the continuing bond to the deceased
      (CB) is proposed. The value of attachment theory in specifying the normative
      course of CB expression and in identifying adaptive versus maladaptive variants
      of CB expression based on their deviation from this normative course is outlined.
      The role of individual differences in attachment security on effective versus
      ineffective use of CB in coping with bereavement also is addressed. Finally, the
      moderating influence of type of loss (e.g., death of a spouse vs. child),
      culture, and religion on type of CB expression within an overarching attachment
      framework is discussed.

PMID- 15849881
TI  - The grief evaluation measure (GEM): an initial validation study.
AB  - This article describes the development of the Grief Evaluation Measure (GEM), a
      new instrument designed to screen for the development of a complicated mourning
      response in a bereaved adult. The GEM provides a quantitative and qualitative
      assessment of risk factors, including the mourner's loss and medical history,
      coping resources before and after the death, and circumstances surrounding the
      death. It is designed to provide an in-depth evaluation of the bereaved adult's
      subjective grief experience and associated symptoms. Reliability and validity
      studies were conducted with two samples of bereaved adults (n = 23 and n = 92,
      respectively) from various clinical and support settings. Data on the two central
      sections of the GEM that assess the mourner's grief response and the level of
      symptomatology are described. Results indicate that the GEM's internal
      consistency and test-retest reliability are high. The GEM demonstrates good
      concurrent validity for established measures of bereavement, trauma, and physical
      and psychiatric symptoms, and good predictive validity for mourner adjustment one
      year after initial assessment. Plans for future development and an invitation for
      other researchers to collaborate with research on the GEM are also discussed.

PMID- 15849882
TI  - Confirmatory factor analysis of the Trinity Inventory of Precursors to Suicide
      (TIPS) and its relationship to hopelessness and depression.
AB  - Numerous existing measures assess attitudes toward suicide yet fail to account
      for contextual factors. The Trinity Inventory of Precursors to Suicide (TIPS) is
      presented as an alternative, with implications for the development of prevention
      programs. Having previously reported exploratory analysis of the TIPS;
      confirmatory factor analysis and predictive validity are examined. Two-hundred
      nineteen males and 454 females aged 15 to 19 years (M = 16.69 yrs; SD = .739 yrs)
      from 11 post-primary schools in Ireland completed a questionnaire consisting of
      the Beck Hopelessness Scale, Beck Depression Inventory, and TIPS. Confirmatory
      analysis revealed an oblique model with good fit for the data. Initial
      psychometric properties and the original factor structure were replicated. The
      authors propose that the context-based information provided by TIPS may be used
      in the development of problem-focused emotional health promotion within the wider
      school setting.

PMID- 15849883
TI  - The narrative labyrinth of violent dying.
AB  - This essay outlines the dynamics of retelling the violent death of a loved one
      and the narrative "dilemma" of vulnerable family members fixated on retelling. To
      counter this fixation, the author presents a mythic retelling of violent death
      (the Myth of Theseus) as narrative basis for developing a restorative retelling.
      The essay begins by exploring the deformed and deforming structure of the violent
      dying story, then details the dynamics of its retelling and concludes by
      presenting a restorative retelling model for family members who cannot release
      themselves from the story for months or years after the violent dying.

PMID- 15849884
TI  - Organ preservation: II.

PMID- 15849885
TI  - [Meteorism].

PMID- 15849886
TI  - Organ preservation: III.

PMID- 15849887
TI  - Neural mechanisms of spatial working memory: contributions of the dorsolateral
      prefrontal cortex and the thalamic mediodorsal nucleus.
AB  - The dorsolateral prefrontal cortex (DLPFC) has been known to play an important
      role in working memory. Neurophysiological studies have revealed that delay
      period activity observed in the DLPFC is a neural correlate of the temporary
      storage mechanism for information and that this activity represents either
      retrospective or prospective information, although the majority represents
      retrospective information. However, the DLPFC is not the only brain area related
      to working memory. The analysis of neural activity in the thalamic mediodorsal
      (MD) nucleus reveals that the MD also participates in working memory. Although
      similar task-related activities were observed in the MD, the directional bias of
      these activities and the proportion of presaccadic activity are different between
      the MD and the DLPFC. These results indicate that, although the MD participates
      in working memory, the way it participates in this process is different between
      these two areas, in that the MD participates more in motor control aspects than
      the DLPFC does.

PMID- 15849888
TI  - Domain specificity in the primate prefrontal cortex.
AB  - Experimental studies in nonhuman primates and functional imaging studies in
      humans have underlined the critical role played by the prefrontal cortex (PFC) in
      working memory. However, the precise organization of the frontal lobes with
      respect to the different types of information operated upon is a point of
      controversy, and several models of functional organizations have been proposed.
      One model, developed by Goldman-Rakic and colleagues, postulates a modular
      organization of working memory based on the type of information processing (the
      domain specificity hypothesis). Evidence to date has focused on the encoding of
      the locations of visual objects by the dorsolateral PFC, whereas the
      ventrolateral PFC is suggested to be involved in processing the features and
      identity of objects. In this model, domain should refer to any sensory modality
      that registers information relevant to that domain--for example, there would be
      visual and auditory input to a spatial information processing region and a
      feature analysis system. In support of this model, recent studies have described
      pathways from the posterior and anterior auditory association cortex that target
      dorsolateral spatial-processing regions and ventrolateral object-processing
      regions, respectively. In addition, physiological recordings from the
      ventrolateral PFC indicate that some cells in this region are responsive to the
      features of complex sounds. Finally, recordings in adjacent ventrolateral
      prefrontal regions have shown that the features of somatosensory stimuli can be
      discriminated and encoded by ventrolateral prefrontal neurons. These discoveries
      argue that two domains, differing with respect to the type of information being
      processed, and not with respect to the sensory modality of the information, are
      specifically localized to discrete regions of the PFC and embody the domain
      specificity hypothesis, first proposed by Patricia Goldman-Rakic.

PMID- 15849889
TI  - Making your next move: dorsolateral prefrontal cortex and planning a sequence of
      actions in freely moving monkeys.
AB  - Prefrontal damage disrupts planning, as measured by disorders of the activities
      of daily living (Humphreys & Forde, 1998; Shallice & Burgess, 1991). In a monkey
      model of this form of planning, a variant of the delayed alternation task was
      performed by freely moving monkeys. In a 16 x 16-ft. testing room, four feeders
      were located in the middle of each wall. In the north task, monkeys alternated
      between feeders: west-north-east-north-west, and so forth. In the south task, the
      alternation sequence was east-south-west-south-east, and so forth. Neuronal
      activity was recorded during walking along the eight paths, constituting the
      north and south tasks. To succeed, monkeys had to memorize the alternation rule
      and monitor both their place in the sequence and the previously made spatially
      directed action before deciding to walk to a new location to the left or right of
      the current location. Responsive dorsolateral prefrontal neurons are strikingly
      selective. Sustained neuronal activity reflects the spatial direction of an
      ongoing or upcoming response. It is important that such selective responses occur
      in one but not both tasks, even though the movements are exactly the same in both
      tasks and at each location. We suggest that selective neuronal activity is tuned
      through learning and reflects the fundamental units of a planning mechanism:
      Individual neurons encode specific components of a sequence of behavioral actions
      and their temporal order. Populations of such neurons represent all the steps
      necessary to perform the north and south tasks. The sustained activity of these
      neurons suggests that planning and working memory mechanisms are integrated.

PMID- 15849891
TI  - Selection from perceptual and conceptual representations.
AB  - The lateral prefrontal cortex has been implicated in a wide variety of functions
      that guide our behavior, and one such candidate function is selection. Selection
      mechanisms have been described in several domains spanning different stages of
      processing, from visual attention to response execution. Here, we consider two
      such mechanisms: selecting relevant information from the perceptual world (e.g.,
      visual selective attention) and selecting relevant information from conceptual
      representations (e.g., selecting a specific attribute about an object from long
      term memory). Although the mechanisms involved in visual selective attention have
      been well characterized, much less is known about the latter case of selection.
      In this article, we review the relevant literature from the attention domain as a
      springboard to understanding the mechanisms involved in conceptual selection.

PMID- 15849890
TI  - The primate working memory networks.
AB  - Working memory has long been associated with the prefrontal cortex, since damage
      to this brain area can critically impair the ability to maintain and update
      mnemonic information. Anatomical and physiological evidence suggests, however,
      that the prefrontal cortex is part of a broader network of interconnected brain
      areas involved in working memory. These include the parietal and temporal
      association areas of the cerebral cortex, cingulate and limbic areas, and
      subcortical structures such as the mediodorsal thalamus and the basal ganglia.
      Neurophysiological studies in primates confirm the involvement of areas beyond
      the frontal lobe and illustrate that working memory involves parallel,
      distributed neuronal networks. In this article, we review the current
      understanding of the anatomical organization of networks mediating working memory
      and the neural correlates of memory manifested in each of their nodes. The neural
      mechanisms of memory maintenance and the integrative role of the prefrontal
      cortex are also discussed.

PMID- 15849892
TI  - Visual attention as a multilevel selection process.
AB  - Natural visual scenes are cluttered and contain many different objects that
      cannot all be processed simultaneously. Therefore, attentional mechanisms are
      needed to select relevant and to filter out irrelevant information. Evidence from
      functional brain imaging reveals that attention operates at various processing
      levels within the visual system and beyond. First, the lateral geniculate nucleus
      appears to be the first stage in the processing of visual information that is
      modulated by attention, consistent with the idea that it may play an important
      role as an early gatekeeper in controlling neural gain. Second, areas at
      intermediate cortical-processing levels, such as V4 and TEO, appear to be
      important sites at which attention filters out unwanted information by means of
      receptive field mechanisms. Third, the attention mechanisms that operate in the
      visual system appear to be controlled by a distributed network of higher order
      areas in the frontal and parietal cortex, which generate top-down signals that
      are transmitted via feedback connections to the visual system. And fourth, the
      pulvinar of the thalamus may operate by integrating and coordinating attentional
      functions in concert with the fronto-parietal network, although much needs to be
      learned about its functional properties. The overall view that emerges from the
      studies reviewed in this article is that neural mechanisms of selective attention
      operate at multiple stages in the visual system and beyond and are determined by
      the visual processing capabilities of each stage. In this respect, attention can
      be considered in terms of a multilevel selection process.

PMID- 15849894
TI  - The role of prefrontal cortex in resolving distractor interference.
AB  - We investigate the hypothesis that those subregions of the prefrontal cortex
      (PFC) found to support proactive interference resolution may also support delay
      spanning distractor interference resolution. Ten subjects performed delayed
      recognition tasks requiring working memory for faces or shoes during functional
      MRI scanning. During the 15-sec delay interval, task-irrelevant distractors were
      presented. These distractors were either all faces or all shoes and were thus
      either congruent or incongruent with the domain of items in the working memory
      task. Delayed-recognition performance was slower and less accurate during
      congruent than during incongruent trials. Our fMRI analyses revealed significant
      delay interval activity for face and shoe working memory tasks within both dorsal
      and ventral PFC. However, only ventral PFC activity was modulated by distractor
      category, with greater activity for congruent than for incongruent trials.
      Importantly, this congruency effect was only present for correct trials. In
      addition to PFC, activity within the fusiform face area was investigated. During
      face distraction, activity was greater for face relative to shoe working memory.
      As in ventrolateral PFC, this congruency effect was only present for correct
      trials. These results suggest that the ventrolateral PFC and fusiform face area
      may work together to support delay-spanning interference resolution.

PMID- 15849893
TI  - Attention and cognitive control as emergent properties of information
      representation in working memory.
AB  - A hallmark of primate, and particularly human, behavior is cognitive control, the
      ability to integrate information from a multitude of sources and use that
      information to flexibly guide behavior in order to achieve an infinite number of
      goals. The neural mechanisms of cognitive control have yet to be fully
      elucidated, although the prefrontal cortex is known to play a critical role.
      Here, I review evidence suggesting that a unifying principle regarding the role
      of various portions of the prefrontal cortex in a wide range of cognitive tasks
      is the active maintenance in working memory of different types of currently
      relevant information-from specific stimulus features, to instructional cues, to
      motivational goals and contexts. I argue that the key to demonstrating the
      existence of this domain-dependent organization lies in a better understanding of
      the nature of the representation of this information and the ways in which this
      information itself controls cognition and behavior.

PMID- 15849896
TI  - Integrating rewards and cognition in the frontal cortex.
AB  - Research indicates that the dorsolateral prefrontal cortex (DLPFC) contributes to
      working memory and executive control, whereas the ventral frontal cortex (VFC)
      contributes to affective and motivational processing. Few studies have examined
      both the functional specificity and the integration of these regions. We did so
      using fMRI and a verbal working memory task in which visual cues indicated
      whether recall performance on an upcoming trial would be linked to a monetary
      reward. On the basis of prior findings obtained in delayed response tasks
      performed by nonhuman primates, we hypothesized that (1) VFC would show an
      increase only in response to a cue indicating potential for a monetary reward;
      (2) DLPFC would show sustained activity across a delay interval for all trials,
      though activity in rewarded trials would be enhanced; and (3) regions engaged in
      speech-based rehearsal would be relatively insensitive to monetary incentive. Our
      hypotheses about DLPFC and rehearsal-related regions were confirmed. In VFC
      regions, we failed to observe statistically significant effects of reward when
      the cue or delay epochs of the task were examined in isolation. However, an
      unexpected and significant deactivation was observed in VFC during the delay
      epoch; furthermore, a post hoc voxelwise analysis indicated a complex interaction
      between (1) the cue and delay epochs of the task and (2) the reward value of the
      trials. The pattern of activation and deactivation across trial types suggests
      that VFC is sensitive to reward cues, and that portions of DLPFC and VFC may work
      in opposition during the delay epoch of a working memory task in order to
      facilitate task performance.

PMID- 15849895
TI  - The effects of prefrontal lesions on working memory performance and theory.
AB  - The effects of experimental lesions of the monkey prefrontal cortex have played a
      predominant role in current conceptualizations of the functional organization of
      the lateral prefrontal cortex, especially with regard to working memory. The loss
      or sparing of certain performance abilities has been shown to be attributable to
      differences in the specific requirements of behavioral testing (e.g., spatial vs.
      non-spatial memoranda) along with differences in the specific locations of
      applied ablations (e.g., dorsal vs. ventral prefrontal cortex). Such findings,
      which have accumulated now for over a century, have led to widespread acceptance
      that the dorsolateral and ventrolateral aspects of the prefrontal cortex may
      perform different, specialized roles in higher order cognition. Nonetheless, it
      remains unclear and controversial how the lateral prefrontal cortex is
      functionally organized. Two main views propose different types of functional
      specialization of the dorsal and ventral prefrontal cortex. The first contends
      that the lateral prefrontal cortex is segregated according to the processing of
      spatial and nonspatial domains of information. The second contends that domain
      specialization is not the key to the organization of the prefrontal cortex, but
      that instead, the dorsal and ventral prefrontal cortices perform qualitatively
      different operations. This report critically reviews all relevant monkey lesion
      studies that have served as the foundation for current theories regarding the
      functional organization of the prefrontal cortex. Our goals are to evaluate how
      well the existing lesion data support each theory and to enumerate caveats that
      must be considered when interpreting the relevant literature.

PMID- 15849897
TI  - The effect of memory load on cortical activity in the spatial working memory
      circuit.
AB  - Accumulating evidence from electrophysiology and neuroimaging studies suggests
      that spatial working memory is subserved by a network of frontal and parietal
      regions. In the present study, we parametrically varied the memory set size (one
      to four spatial locations) of a delayed-response task and applied time-resolved
      fMRI to study the influence of memory load upon the spatial working memory
      circuit. Our behavioral results showed that performance deteriorates (lower
      accuracy and longer reaction time) as memory load increases. Memory load
      influenced cortical activity during the cue, delay, and response phases of the
      delayed-response task. Although delay-related activity in many regions increased
      with increasing memory load, it also was significantly reduced in the middle
      frontal gyrus and frontal eye fields and leveled off in the parietal areas when
      memory load increased further. Delay-related activity in the left posterior
      parietal cortex was also lower during the error trials, in comparison with the
      correct trials. Our findings indicate that the delay period activity in the
      spatial working memory circuit is load sensitive and that the attenuation of this
      signal is the neural manifestation of performance limitation in the face of
      excessive memory load.

PMID- 15849898
TI  - How we use rules to select actions: a review of evidence from cognitive
      neuroscience.
AB  - Much of our behavior is guided by rules, or prescribed guides for action. In this
      review, I consider the current state of knowledge of how rules are learned,
      stored in the brain, and retrieved and used as the need arises. The focus is
      primarily on studies in humans, but the review is informed by relevant studies in
      nonhuman primates. Ventrolateral prefrontal cortex (VLPFC) has been implicated in
      rule learning, retrieval from long-term memory, and on-line maintenance during
      task preparation. Interactions between VLPFC and temporal cortex are required for
      rule retrieval in nonhuman primates, and brain imaging findings in humans suggest
      that rule knowledge is stored in the posterior middle temporal gyrus.
      Dorsolateral PFC appears to be more closely related to rule-based response
      selection than to rule retrieval. An important task for the future is to explain
      how PFC, basal ganglia, and temporal, parietal, and motor cortices interact to
      produce rule-guided behavior.

PMID- 15849900
TI  - Prefrontal cortex and the mediation of proactive interference in working memory.
AB  - Mediating proactive interference (PI), the deleterious effect of antecedent
      information on current memory representations, is believed to be a key function
      of prefrontal cortex (PFC). Item-specific PI results when an invalid probe
      matches a memorandum from the preceding trial; item-nonspecific PI is produced by
      the accumulation of no-longer-relevant items from previous trials. We tested the
      hypothesis that these two types of PI are mediated by common PFC-based processes
      with an fMRI study of a delayed-recognition task designed to produce both types
      of PI. Our results indicated that the fMRI correlates of both effects were
      restricted both to Brodmann's area 45 in the left hemisphere and to the memory
      probe epoch of the trial. These results suggest that a unification of the
      literatures and approaches that have independently studied these phenomena might
      offer a fruitful new perspective from which to study the relations between
      working memory, executive control, and the PFC.

PMID- 15849899
TI  - Functional connectivity during working memory maintenance.
AB  - Neurophysiological experiments with monkeys have demonstrated that working memory
      (WM) is associated with persistent neural activity in multiple brain regions,
      such as the prefrontal cortex (PFC), the parietal cortex, and posterior unimodal
      association areas. WM maintenance is believed to require the coordination of
      these brain regions, which do not function in isolation but, rather, interact to
      maintain visual percepts that are no longer present in the environment. However,
      single-unit physiology studies and traditional univariate analyses of functional
      brain imaging data cannot evaluate interactions between distant brain regions,
      and so evidence of regional integration during WM maintenance is largely
      indirect. In this study, we utilized a recently developed multivariate analysis
      method that allows us to explore functional connectivity between brain regions
      during the distinct stages of a delayed face recognition task. To characterize
      the neural network mediating the on-line maintenance of faces, the fusiform face
      area (FFA) was defined as a seed and was then used to generate whole-brain
      correlation maps. A random effects analysis of the correlation data revealed a
      network of brain regions exhibiting significant correlations with the FFA seed
      during the WM delay period. This maintenance network included the dorsolateral
      and ventrolateral PFC, the premotor cortex, the intraparietal sulcus, the caudate
      nucleus, the thalamus, the hippocampus, and occipitotemporal regions. These
      findings support the notion that the coordinated functional interaction between
      nodes of a widely distributed network underlies the active maintenance of a
      perceptual representation.

PMID- 15849902
TI  - [Significance of the scientific work of Dr. Carlos J Finlay on the 170th
      anniversary of his birth].

PMID- 15849901
TI  - Temporal kinetics of prefrontal modulation of the extrastriate cortex during
      visual attention.
AB  - Single-unit, event-related potential (ERP), and neuroimaging studies have
      implicated the prefrontal cortex (PFC) in top-down control of attention and
      working memory. We conducted an experiment in patients with unilateral PFC damage
      (n = 8) to assess the temporal kinetics of PFC-extrastriate interactions during
      visual attention. Subjects alternated attention between the left and the right
      hemifields in successive runs while they detected target stimuli embedded in
      streams of repetitive task-irrelevant stimuli (standards). The design enabled us
      to examine tonic (spatial selection) and phasic (feature selection) PFC
      extrastriate interactions. PFC damage impaired performance in the visual field
      contralateral to lesions, as manifested by both larger reaction times and error
      rates. Assessment of the extrastriate P1 ERP revealed that the PFC exerts a tonic
      (spatial selection) excitatory input to the ipsilateral extrastriate cortex as
      early as 100 msec post stimulus delivery. The PFC exerts a second phasic (feature
      selection) excitatory extrastriate modulation from 180 to 300 msec, as evidenced
      by reductions in selection negativity after damage. Finally, reductions of the N2
      ERP to target stimuli supports the notion that the PFC exerts a third phasic
      (target selection) signal necessary for successful template matching during
      postselection analysis of target features. The results provide
      electrophysiological evidence of three distinct tonic and phasic PFC inputs to
      the extrastriate cortex in the initial few hundred milliseconds of stimulus
      processing. Damage to this network appears to underlie the pervasive deficits in
      attention observed in patients with prefrontal lesions.

PMID- 15849903
TI  - [Design of an agglutination latex test to detect venoms from Viperidae snakes in
      patients' serum].
AB  - This latex agglutination test was designed as a tool in the diagnosis of the
      ophidic accidents The development of specific trials to identify venoms from the
      most common snakes inVenezuela in human sera, could contribute to the improvement
      of the diagnosis of these accidents caused by snakes of the Bothrops and Crotalus
      genera, and in the control of the antiophidic serum for the treatment in an
      adequate and immediate way. The results obtained revealed a sensitivity of 167
      mg/mL with good specificity, rapidity (10 minutes) and simplicity, since it can
      be accomplished by personnel with a basic training and only a microscope is
      necessary. All these reasons show the potential of this technique. It is required
      to complement the results with studies of the different factors that take part in
      the making of the latex reagent and that allow to improve its quality. Among
      these modifications it is suggested to improve the detection of smaller
      quantities of venom, to prove the recognition of the specific immunoglobulin
      sensitized latex particles against the Bothrops and Crotalus venbm, and to
      reproduce the test at the clinical level by using serum from patients that have
      been victims of ophidic accidents.

PMID- 15849904
TI  - [Identification of yeasts in pap smears: clinical characteristics associated with
      candidiasis].
AB  - A study of 404 women that attended the Microbiology Laboratory of Ramon Gonzalez
      Coro Gynecoobstetric Hospital, in Havana City, was conducted aimed at identifying
      species of yeasts isolated from Pap smears, registering the signs and clinical
      symptoms and determining the risk factors associated with infection. The isolated
      yeasts were identified by the filamentation tests in serum, production of
      chlamydoconidia and carbohydrate assimilation. It was found that 138 (34.16%) of
      women had yeasts in the vagina. 3 genera were identified: Candida (88.49%).
      Trichosporon (10.79%) and Rhodotorula (0.72%). Pruritus and heat showed
      statistical significance (p < 0.01). Pregnancy, the use of IUD and the
      antibacterial therapy proved to be the most common risk factors in relation to
      the presence of Candida in the vagina.

PMID- 15849905
TI  - [Immunogenecity induced by the VA-MENGOC-BC antimeningococcal vaccine against the
      ATCC C11. N. meningitidis strain in adolescents 12 years after being vaccinated].
AB  - The antibodies' response induced by the VA-MENGOC-BC Cuban antimeningococcal
      vaccine against the ATCC C11 strain was studied by Bactericidal Serum Trial and
      ELISA among 184 adolescents from a polytechnic, in Ciego de Avila, that had been
      immnunized in mass campaings 12 years before. Blood samples were taken before
      administering the first dose (T0), 4 weeks later (T1), and 4 weeks after the
      second dose (T2). 12 years after vaccination, 25% of the adolescents presented
      bactericidal titers > or =1:8 against the evaluated strain. 78% showed a
      concentration of antibodies over the limit of detection against the meningococcus
      C capsular polyssacharide. The percentages of seroconversion after the first dose
      were 59 by Bactericidal Serum Trial and 82 by ELISA. There were no significant
      differences (p > 0.05) between the results obtained after the first and second
      dose by boths trials. The reimmnunization with 2 doses of the vaccine did not
      cause hyporesponse against the ATCC C11 strain in this age group.

PMID- 15849906
TI  - [Surveillance in children of mothers positive to hepatitis B surface antigen,
      2000-2002].
AB  - This study was made as part of the Surveillance Program that has been implemented
      for 10 years for the perinatal control of hepatitis B in children of positive
      mothers. The control of hepatitis B is possible thanks to the existance of the
      vaccines against this entity. In Cuba, there is a safe and effective vaccine for
      its prevention. The perinatal infection risk among children of mothers positive
      to hepatitis B surface antigen (HbsAg) is high. Many of these infections may be
      prevented if mothers positive to HbsAg are early detected and their children are
      vaccinated at birth. 121 serum samples from positive mothers and their respective
      7-month-old children from all over the country that were received at the National
      Viral Hepatitis Reference Laboratory of "Pedro Kouri" Tropical Medicine Institute
      were studied from September to December, 2000. All the samples underwent the test
      to detect HbsAg and anti-HBs antibodies were investigated in children negative to
      HbsAg. 100% of positivity to HBsAg was found among mothers. 5.7% of positivity to
      this antigen was obtained in children. In negative children the seroprotection
      attained in this group was 94.7% with an anti-HBs Geometric Mean Titer (GMT) of
      233.3 UI/L. The normoresponsive children predominated with 52.6%. The Efficacy
      Index of the vaccine used ranged from 95.9% to 99.3%.

PMID- 15849907
TI  - [Tuberculosis and AIDS: various clinical and epidemiological aspects in 72 Cuban
      patients].
AB  - 72 AIDS patients with tuberculosis diagnosis discharged from "Pedro Kouri"
      Tropical Medicine Institute between January, 1997, and March, 2001, were included
      in the research aimed at studying tuberculosis in HIV/AIDS patients. A
      descriptive and retrospective design was used and clinical, epidemiological and
      microbiological variables were described. The CD4 T lymphocytes count was also
      determined. Males prevailed (72.2% of the cases) with an average age of 30.83
      years old and 4.82 average years between the HIV serodiagnosis and tuberculosis.
      In 48.6% of the cases, AIDS was defined due to tuberculosis. Cough,
      expectoration, fever of unknown origin, night sweating and weight loss were the
      most frequent symptoms. The mean CD4 count was 179 cells per mm3. 76.4% had less
      than 200 cells per mm3 (p < 0.05). Pulmonary tuberculosis was the form of
      presentation in 79.2% of the patients without association with the
      immunosuppresion degree. The chest X-ray showed alterations in 83.3% of the
      cases, the inflammatory infiltrate of the bases, and the mediastinal and pleural
      taking were the most representative. The positivity rate of baciloscopy was
      45.8%, whereas the culture was positive in 62.4% of the patients (p < 0.05). The
      results of the previous tests were not significantly associated with the mean CD4
      count. Anergy to tuberculin was reported in 50 patients (69.4%) (p < 0.05). The
      CD4 mean in the anergic patients (109 cells) was markedly lower than in the rest
      (403 cells) (p = 0.0009).

PMID- 15849908
TI  - [Obtention and characterization of a diploid cell line of human kidney].
AB  - A new diploid cell line of human embrionary kidney was obtained by serial
      subcultures (Mag) starting from a primary culture. It was prepared by applying
      the explant technique instead of the classical enzymatic digestion with trypsin.
      The stabilization process of the diploid line after the "secondary culture" was
      attained between the passes 6 and 7. 3 culture media were tested during the
      process. Only the MEM was completely satisfactory. The biological characteristics
      of the new line were as follows: fibroblastic morphology, Eagle MEM culture mean
      with 10% of SBF, split from 1:2 to 1:3, normal human carotype, postfreezing
      viability of 60%, pollutant-free and non-tumorigenic. The cryopreserved Mag
      subcultures 11-13 were studied from the point of view of their usefulness for the
      diagnosis of different viral groups.

PMID- 15849909
TI  - [Quality control of the diagnosis of malaria in the province of Cienfuegos,
      Cuba].
AB  - Data were collected by surveying all the technicians that worked at the different
      primary and secondary health care units. A quality control was carried out in the
      diagnosis of paludism in the 18 laboratories of the province of Cienfuegos.
      Various parameters were controlled. The method A considered 4 aspects to be
      evaluated: preparation of the material, sample taking, staining and microscopy.
      The method B consisted in an efficiency test by the observation of a set of
      laminae negative and positive to Plasmodium vivax and Plasmodium falciparum. In
      both cases, it was established a scoring scale. Besides, the physical conditions
      of the laboratory, the personnel permanence, as well as the time of experience in
      the diagnosis of paludism, were taken into account. The best results were
      obtained with the fixed personnel working in the paludism section. It was proved
      with a statistical significance level that the good category predominated for
      methods A and B after evaluating all the technicians. The study showed a better
      preparation of the personnel with less than 5 years of experience, which was
      related to the participation in the training course conducted at the provincial
      level by "Pedro Kouri" Tropical Medicine Institute 6 months before the
      investigation. Deficiencies were found in the conditions of the clinical and
      microbiology laboratories.

PMID- 15849910
TI  - [Resistance to insecticides in larvae and adults of Aedes aegypti, Havana City:
      prevalence of A4 esterasa associated with resistance to temephos].
AB  - 2 strains of Aedes aegypti from 2 people's councils with high indexes of
      infestation of this vector were studied due to the need of carrying out an
      effective control of larvae and adults in the municipality of Guanabacoa. The
      levels of susceptibility and/or resistance to organophosphate insecticides,
      pyrethroids and a carbamate were determined. The results of the bioassays in
      larvae showed a complete susceptibility to organophosphate insecticides,
      malathion, clorpirifos, methyl-pyrimifos and propoxur carbamate in both people's
      councils. However, it was observed a high resistance to temephos and fenthion. No
      resistance to fenitrothion was found in one of the people's councils. At the
      adult stage and at the dose recommended by the World Health Organizaton or by the
      product manufacturers, it was observed resistance to malathion, fenitrothion and
      propoxur; nevertheless, better results were obtained with the pyrethroids, with
      mortality percentages over 90%. According to the results obtained, by using the
      SSS tributyl phosphotritiade sinergist (DEF) and piperonyl butoxide, it was
      demonstrated that the multiple function esterases and oxidases played an
      important role in the resistance to temephos and fenthion. It was proved that he
      amplified activity of these enzymes was at an elevated frequency in both people's
      councils, the same as the glutathione transferase (GST) in one of the 2 people's
      councils. It was observed that in both people's councils prevailed the amplified
      activity of A4 esterases by polyacrylamide gel electrophoresis.

PMID- 15849911
TI  - [Status of resistance to insecticides and resistance mechanisms in larvae from
      Playa municipality collected during the intensive campaign against Aedes aegypti
      in Havana City, 2001-2002].
AB  - The levels of susceptibility and/or resistance to inseciticides in Aedes aegypti
      larvae collected at the municipality of Playa during the intensive campaign
      against the mosquito Aedes aegypti, in Havana City, in the present year, were
      determined. In larvae, it was found a high resistance to the organophosphate
      insecticides phention and temephos and moderate to fenitrothion. A high
      resistance to propoxur carbamate was also detected. The larvae proved to be
      susceptible to clorpirifos, malathion and methylpyrimifos. The results obtained
      through the use of sinergists indicated that esterases play an important role in
      the detected resistance to organophosphate insecticides, but not in the
      resistance to propoxur. However, the monooxigenases take part only in the
      resistance to fenitothrion. These mechanisms were found at an elevated frequency
      in the larvae from this municipality. It was confirmed the role played by
      esterases in the resistance to temephos by polyacrilamide gel inhibition tests.

PMID- 15849912
TI  - [Serological diagnosis of syphilis in Cuban HIV/AIDS patients].
AB  - The non-treponemic fast detection test of plasmatic reagines (RPR) and the
      treponemic hemagglutination test of Treponema pallidum were used in the detection
      of infection due to T. pallidum in 60 males presenting HIV/AIDS infection with
      clinicoepidemiological diagnosis of syphilis. It was confirmed that 30% presented
      recently acquired symptomatic or latent syphilis and that 10% had markers of past
      treated infection or of late acquired latent syphilis, whereas in the other 60%
      no serological reactivity was detected. A seroprevalence study of reaginic
      antibodies was conducted by RPR in 59 HIV/AIDS females, using 67 women negative
      to this virus as controls. All of them had no symptoms compatible with the
      syphilitic infection. It was concluded that 20.3% and 11.9%, respectively,
      presented reactivity, which established a probable diagnosis of syphilis or a
      seroresistance to a previouos syphilis. These results showed a close association
      between syphilis and HIV/AIDS and that both diseases may coexist in a same
      patient.

PMID- 15849913
TI  - [Antiretroviral therapy in HIV/AIDS seropositive pregnant women in Cuba].
AB  - It was assessed that the number of HIV infected children due to vertical
      transmission increases every day and that is why the early diagnosis in the HIV+
      pregnat women and the administration of antivirals in the prenatal stage to
      reduce the transmission is so important. Taking these factors into account, from
      1997 on, it was decided in Cuba to administer AZT to all HIV+ pregnant women and
      to the newborn infant, as it is established in the protocol 076, which
      considerably reduced the number of infected children.

PMID- 15849914
TI  - [Morphological and histological comparison of the digestive tract of Gambusia
      puncticulata and Girardinus metallicus, fishes used in the biological control of
      mosquitoes].
AB  - The morphology and histology of the digestive tract of Gambusia puncticulata and
      Girardinus metallicus fishes used in the biological control of mosquito larvae in
      Cuba, were described and compared. They were related to the food habits of each
      species. Gambusia puncticulata has a short and thick intestine, which is
      characteristic of the carnivorous species, whereas Girardinus metallicus has an
      elongate and thin spiral rolled up intestine as it corresponds to the omnivorous
      fishes. It was observed that the histological pattern of the intestine in both
      species is very simple; however, Gambusia puncticulata presented a great number
      of ramified microhairiness on comparing it with Girardinus metallicus, which
      increases this way the digestive yield of its relatively shorter digestive tract.

PMID- 15849915
TI  - [Usefulness of D-proline in the differentiation of varieties of Cryptococcus
      neoformans].
AB  - A comparative study was conducted between the assimilation of D-proline and the
      growth on canavanine-glycine-bromothymol blue (CGB) medium used for the
      classification of the varieties of Cryptococcus neoformans. In the 86 studied
      strains, 100% of coincidence between both methods allowed to affirm that 95.34%
      corresponded to the neoformans var. and the rest (4.65%) to the gattii var. The
      results obtained corroborated that all the autoctonous clinical isolations up to
      the present correspond to the. neoformans var. and made possible to suggest the
      use of D-proline for the initial evaluation of strains, as an alternative and
      simple method that presented under these conditions high coincidence with the
      reference method (growth in CGB).

PMID- 15849916
TI  - [Application of the nucleotidic sequencing of VP1 to the identification of human
      Enterovirus].
AB  - The introduction of a mollecular method to identify the Entoviruses based on the
      amplification sequecing and phylogenetic analysis of protein VPI was described.
      It was proved that this method reduces significantly the time required for the
      identification of the isolated Entoviruses and that it is very useful in the
      characterization of isolates which are difficult to typify by the routine
      immunoloigical reagents. As it is a very fast technqiue, its use is very
      important during epidemics to determine the causal agent rapidly.

PMID- 15849917
TI  - [In vitro susceptibility of vaginal isolates of Candida vs clotrimazole and
      nystatin].
AB  - The susceptibility in vitro of 123 isolates of Candida against clotrimazole and
      nystatin was determined. The isolates were obtained by vaginal smears from 404
      women that attended "Ramon Gonzalez Coro" Gynecoobstetric Hospital, in Havana
      City According to the number of colonies obtained in the primary isolation, the
      strains were separated into 2 categories: colonization and infection. The
      inhibitory minimum concentration (IMC) was detemined for each antigunfal by a
      method of microdilution in casitone broth. The geometrical means of the IMC
      values were higher against nystatin (1.08 mg/mL) than against clotrimazole (0.22
      mg/mL), eventhough the features were similar (< or = 0.125-16 mg/ml,) For
      (Candida albicans, that was the most frequently isolated species (54.5 %), the
      geometrical means of the IMC values were 0.17 and 0.16 mg/mL for clotrimazole and
      0.71 and 0.92 for nystatin, in both categories. C glabrata showed the highest IMC
      values (16 mg/mL) against antifungals. Only the isolates of C. lusitaniae showed
      a significant difference (p < 0.001) between the IMC values of nystatin according
      to the number of colonies in the primary isolation. In isolates from women
      treated with clotrimazole and/or nystatin in previous episodes of candidiasis,
      there were observed more elevated values of the means of IMC against nystatin
      than against clotrimazole, although this difference was not statistically
      remarkable.

PMID- 15849918
TI  - [Microbiological characterization of candidate vaccine strains of Ballum
      serogroup Leptospira interrogans].
AB  - Two candidate vaccines of Ballum serogroup Leptospira interrogans were
      microbiologically characterized as part of the work directed to the obtention of
      new antileptospirosis vaccine formulations for human use. The growth kynetics of
      both strains was evaluated in EMJH protein medium and in 3 protein free media.
      The virulence was estimated in hamsters by the calculation of the mean lethal
      dose. The cellular and extracellular antigenic profiles were analyzed by
      unidimensional SDS-PAGE and compared with those from strains of Canicola,
      Icterohaemorrhagiae and Pomona serogroups. The antigenic homology among
      heterologous groups was analyzed by western blotting with serun from hasterms
      vaccinated with vax-SPIRAL. The results obtained showed a fastidious growth of
      both strains of Ballum in the studied media, a high virulence in the animal model
      and a large antigenic homology with strains from other serogroups of Lepstospira
      prevailing in Cuba.

PMID- 15849919
TI  - [Methicillin-resistant Staphylococcus aureus. Detection of carriers among
      hospitalized children and healthy children from the community].
AB  - A descriptive punctual study was conducted to search for nasal carriers of
      Staphylococcus aureus strains resistant to methycilin (SARM) among sound children
      attended in nurseries and hospitalized children exposed to one or more risk
      factors predisposing to the colonization by this type of strains from October,
      2000, to February, 2001, in Marianao municipality. For the primary isolation of
      the SARM strains, it was used the oxacillin-manitol-salt-agar (OMSA) and the
      sensitivity to antimicrobial drugs was determined in all strains identified as S.
      aureus by using the Kirby-Bauer method. In order to identify the resistance to
      oxacillin in the strains recovered from OMSA, the oxacillin salt-agar screening
      plate method and the determination of inhibitory minimum concentration (IMC) in
      agar and broth were applied. The presence of the mecA gene was nvestigated by
      polymerase chain reaction in those strains with an IMC > or = 4 mg/mL of
      oxacillin. Of the sound children. 0.35 % and of the hospitalized, 2 %, were nasal
      carriers of SARM strains. The strains isolated in both study groups showed high
      indexes of resistance to penicillin, tetracycline and erythromycin by the Kirby
      Bauer method. The mecA gene was identified in a SARM strain isolated from a
      hospitalized nasal carrier and it was defined that its behaviour agreed with the
      one described for a strain homoresistant to oxacillin.

PMID- 15849920
TI  - [Carriers of Neisseria meningitidis among children from a primary school].
AB  - A cross-sectional and descriptive study was conducted among 318 children from the
      "Martires del Corynthia" Primary School under the authorization of the Municipal
      Division of Education and the informed consent of their parents aimed at knowing
      the prevalence of meningoccoco carriers in school children, determining the
      epidemiological markers of the isolated strains and establishing the possible
      relation existing between the carrier and variables, such as age, sex, acute
      respiratory infection history, hacinamiento, amigdalectomy, inhibitory effect of
      of the accompanying flora and the secretory state of ABH antigens in saliva. All
      of them underwent nasopharyngeal exudate and a saliva sample was taken. In
      adition, the paents were surveyed about the risks factors to be investigated. 6.9
      % of meningoccoco carriers were found and the NA:NT:P1:NST:L3,7,9 strains
      predominated. The risk factors with statistically significant results regarding
      the condition of carrier Neisseria meningitidis carrier were age, acute
      respiratory infection history, and the presence of Streptococcus pneumoniae and
      Neisseria lactamica of the accompanying bacterial flora in the nasopharynx of the
      children under study.

PMID- 15849921
TI  - [Preliminary evaluation of the antiviral activity of the aqueous extract of
      Phyllanthus orbicularis vs HIV-1 infection].
AB  - The antiviral activity of the aqueous extract of Phyllanthus orbicularis, a
      member of the Euohorbiacea family, against the simple herpes virus typel was
      evaluated in cellular culture, specifically in fibroblasts of human prepucium,
      and in an animal model, Balb-c mice. The extracelullar effect of the extract on
      HIV-1 proved to be effective. A selective index of 44 was obtained, which shows a
      possible virucidal action on the particle. In the trial in vivo, the topical
      administration of the aqueous extract (12 mg/kg) reduced significantly the
      development of lesions in mice subcutaneously infected with HIV-1 (1 x 106 UFP).
      These results suggest the consideration of Phyllanthus orbicularis as a possible
      anti-HIV-1 candidate

PMID- 15849922
TI  - [Usefulness of 2 coproparasitological methods and their utilization in an
      antigiardiasis therapeutic trial].
AB  - A study of 456 children aged 1-5 from 4 day care centers of San Miguel del Padron
      municipality was conducted in 1998, to evaluate the diagnosis of Giardia lamblia
      and other intestinal protozoa by using comparatively the coproparasitological
      diagnostic methods of direct examination and Ritchie's concentration technique or
      formol-ether. Besides, a therapeutical trial was developed with tinidazole and
      albendazole for treating the infection caused by G lamblia. Ritchie's
      concentration technique was more effective than the microscopic direct
      examination for diagnosing Giardia lamblia, Entamoeba histolytical/Entamoeba
      dispar and Cyclospora cayetanensis. It was demonstratyed that the serial
      examination was more sensitive than the analysis of just one sample (p< 0.01). On
      the other hand, tinidazole proved to be more efficient than albendazole to treat
      the infection produced by G. lamblia, with a greater cure percentage (72 % vs.
      334.6%), (p < 0.01).

PMID- 15849923
TI  - [Behavior of vaginal trichomoniasis in a group of adolescents].
AB  - 275 adolescents aged 10-19 receiving attention at the infantojuvenile department
      of pregnancy interruption and of sexually transmitted infections of "Ramon
      Gonzalez Coro" and "Eusebio Hernandez" Gynecoobstetric Teaching Hospitals, both
      in Havana City, were studied from August, 1999, to September, 2000, aimed at
      knowing the behavior of the infection caused by Trichomonas vaginalis in this
      population group. The results yielded 18.1 % of positivity to parasitosis. It was
      proved by the calculation of relative risk that the adolescents that had an
      active or past infection due to Trichomonas vaginalis have more possibilities of
      getting an infection produced by human Papilomavirus than those without this
      condition. It was demonstrated that 78 (28.3 %) of the total of patients examined
      had some type of lesion in the uterine cervix. Some risk factors as non using
      condon, having multiple sexual partners and the early beginning of sexual
      relations, which may facilitate the adquisition of this parasitosis in a
      population so vulnerable as the adolescents, were made known.

PMID- 15849924
TI  - [Knowledge, believes and practices of physicians from Cienfuegos in relation to
      intestinal amebiasis: results of an intervention].
AB  - In a study conducted in the province of Cienfuegos, it was proved by using
      immunological and biomolecular tools that intestina amebiasis in that province
      was an overdimensioned health problem. A survey on knowledge, perceptions and
      practices applied to those physicians related to the diagnosis, treatment and
      control of this parasitosis showed that the overdimensioning may be associated
      with an inadequate perception of the problem and with a marked lack of knowledge
      about important aspects of this entity. To contribute to the solution of the
      ovedimensioning and of its consequences, a set of actions were taken in that
      province. After a year, a second survey was done, whose results are published in
      this document, allowing to know about a significant improvement of the surveyed
      in almost all the evaluated cognitive and perceptual aspects (6.73 and 11.23
      means of correct answers before and after the intervention, respectively).

PMID- 15849925
TI  - [Levels of resistance to insecticides and their mechanisms in 2 strains of Aedes
      aegypti from Panama].
AB  - The levels of susceptibility and/or resistance to insecticides in larvae and
      adults of Aedes aegypti from 2 localities of Panama (Rio Abajo and Victoriano
      Lorenzo) were determined. Among larvae, it was found resistance to methyl-
      pyrimifos in both localities; however, they were susceptible to the rest of the
      organophosphate insecticides (temephos, malathion, fenthion fenitrothion and
      clorpirifos) and to pyrethroids (deltamethrin, lambda-cyhalothrin, cypermethrin
      and cyfluthrin. In the trials carried out in adults, according to the categories
      of the World Health Organization, the 2 localities proved to be completely
      susceptible to deltamethrin, lambda-cyhalothrin, beta cypermethrin and
      cyfluthrin.

PMID- 15849926
TI  - [Status of resistance to insecticides in field strains of the Blatella germanica
      species (Dictyoptera: Blattellidae) from Pinar del Rio municipality].
AB  - A study of the levels of resistance to 10 insecticides: 4 organophosphate
      compounds (malathion, clorpirifos, methylpyrimifos and diazinon), 2 carbamates
      (propoxur and bendiocarb) and 4 pyrethroids (cypermethrin, deltamethrin,
      lamdacyhalothrin and cyfluthrin) was conducted in 5 strains of Blatella germanica
      (Linnaeus, 1767) collected in the field of Pinar del Rio. High levels of
      resistance to bediocarb, cypermethrin and deltamethrin insecticides; low level of
      resistance to diazinon; from moderate to high resistance to methyl-pyrimifos, as
      well as susceptibility to one insecticide in each study group: clorpirifos
      (organophosphate), propoxur (carbamate) and cyfluthrin (pyrethroid); were
      detected. Only a strain presented low resistance to malathion (Inicio Carlos
      Manuel) and to lambda-cyhalothrin (Consejo Celso Maragoto). Cypermethrin
      deltamethrin cross resistance was evidenced. It did not affect the susceptibility
      to lambda-cyalothrin and cyfluthrin.

PMID- 15849927
TI  - [Amplification at random of the DNA from 5 Cuban populations of larviphage fishes
      of the Rivulus genus].
AB  - DNA from 10 individuals from 5 populations of Rivulus collected in the western
      region of Cuba was amplified at random. No monomorphic marker resulted from the
      amplification by using 5 primers, which showed the high genetic variability
      existing among the fishes of the 5 populations. According to the genetic distance
      among the individuals, they were divided into 4 groups, for which there are
      specific genetic markers of RAPD, since they are not observed in the rest of the
      subjects. These results support the use of RAPD as an efficient tool for the
      genetic characterization of Cuban fishes of the Rivulus genus.

PMID- 15849928
TI  - Aeromonas: an emerging pathogen associated with extraintestinal infection in
      Cuba.
AB  - An 87 years-old female with a history of heart disease who has been presenting
      dysnea and fever for 2 months was evaluated. A sputum bacteriological study
      proved positive for Aeromonas hydrophila in the context of an existing lung
      cancer. The study was negative for acid fast bacilli.

PMID- 15849929
TI  - [Evaluation of a semisolid medium for preserving microorganisms of the
      Enterobacteriaceae family].
AB  - 26 bacterial strains from the Enterobacteriaceae family were studied to evaluate
      the maintenance of the cultural. tinctorial and biochemical properties of the
      microorganisms originally preserved in the semisolid medium of conservation since
      the end of the 1980's. 22 of them were viable, showing their survival for more
      than 10 years. The microorganisms have been maintained in this medium since their
      introduction into the Laboratory of Collection of Microbial Cultures of the
      National Institue of Hygiene. Epidemiology and Microbiology of Cuba. They have
      been used as pattern strains in the internal control of the quality, of reagents
      and culture media produced in this center for their further use in the
      microbiological evaluation of environmental samples This medium gives good
      results for the conservartion of strains of Enterobaceriaceae and may be used in
      laboratories with scarce resources.

PMID- 15849930
TI  - [Application of SensiScript enzyme to a RT-PCR system for the obtention of RNA of
      HIV-1 starting serum samples stored at -20 degrees C during a decade].
AB  - The efficiency of SensiScript reverse transciptase to obtain useful genetic
      material in the sequencing of the nucleic acid from HIV-1, starting from sera
      collected between 1989 and 1998 and kept at suboptimal temperatures, was proved.
      On using the SensiScript enzyme it was obtained an amplification of the RNA of
      the HIV-1 in 86.5 % of the studied samples, compared with 20 % on using the AMV
      RT enzyme . No amplification was obtained in 13.5 % of the studied samples with
      any of the 2 enzymes used.

PMID- 15849931
TI  - [Determination of morphotypes of Candida spp. in vaginal smears].
AB  - Samples of vaginal smears were taken from 100 patients suspected of vaginal
      candidiasis that attended the Microbiology Laboratory of "Freyre de Andrade"
      Clinical and Surgical Hospital, in Havana City. These samples were cultivated in
      Sabouraud agar and Sabouraud triphenyltetrazolium agar (STA). In 45 % of the
      samples it was observed growth of the yeast-shaped colonies, where Candida
      albicans (51.1 %) and C. glabrata (22.2 %) were the most frequently isolated
      species. It was proved that STA allowed to differentiate the morphotypes of the
      yeast species and it was observed that most of the species presented more than
      one morphotype with the predominance of flat light pink colonies without mycelial
      halo in C. albicans, C. glabrata did not grow in it. This phenotypic typing in
      STA will permit to approach epidemiological studies in a future.

PMID- 15849932
TI  - [Frequency of Trichomonas vaginalis infection in couples with fertility
      problems].
AB  - One-hundred and seventy two couples which went for the first time to the
      Infertility Service of the National Institute of Endocrinology from June 1999 to
      June 2000, were studied to find out the frequency of Trichomonas vaginalis
      infection in this group, and determine its interaction with a number of clinical
      and risk variables. The results yielded that 10.5% were positive to the parasite,
      the prevailing symptom was leukorrea in women and 96.6% of men showed no
      symptoms. It was highly significant the fact of having a previous pathological
      history that might be related to infertility and current T. vaginalis infection.
      This protozoon was frequently associated with Candida sp. and causative agents of
      bacterial vaginosis in women and Haemophilus influenzae in men. This parasite
      seems to play an important role as a likely causative agent to be considered in
      fertility problems.

PMID- 15849933
TI  - [Legionella pneumophila: extraction of the main protein from the outer membrane
      (p29)].
AB  - Legionella pneumophila is an important opportunistic pulmonary pathogen that
      causes Legionaires'diseases. In the outer membrane of the bacterium, there is a
      protein with molecular weight of 29 kD(p 29), which is not only an specific
      antigen of the species but also the major outer membrane protein; it may also be
      a factor of pathogenecity in the bacterium. The main objective of this paper was
      the extraction and purification of this protein by treating the outer membrane
      with chemical agents. A p 29-rich semipurified antigen extract was obtained that
      can be used as an important antigen for the development of immunodiagnostic
      techniques in future studies and also for obtaining a monoclonal antibody to be
      used for the same purpose.

PMID- 15849934
TI  - [Evaluation of the activity of polymorphonuclear neutrophils against Entamoeba
      histolytica antigens].
AB  - This paper evaluates the production of superoxide as an indicator of the activity
      of neutrophils from healthy individuals, stimulated with Entamoeaba histolytica
      membrane antigens, chemical stimulators and antigens from other parasites. The
      kinetic nitroblue tetrazolium reduction test was used. No significant differences
      were observed in the control group as to superoxide production by neutrophils
      primed with Entamoeba histolytica antigens or Cisticercus cellulosae, Toxoplasma
      gondii and Giardia lamblia antigens. These results allow us to conclude that
      Entamoeba histolytica membrane antigens do not induce superoxide production by
      neutrophils, which contradicts previous statements on suppresed activity of
      neutrophils after they get in contact with Entamoeaba histolytica antigens.

PMID- 15849935
TI  - [Antiamebic effect of metronidazole proved in a study conducted in Cienfuegos
      province].
AB  - Three studies were conducted in Cienfuegos province to prove that intestinal
      amebiasis in Cuba could be an overestimated health problem. The first two studies
      showed two components of this overestimation: microscopical overdiagnosis and
      lack of knowledge about Entamoeba dispar, a non-pathogenic species, in most cases
      in which microscopical examination was correct. This paper reported the third
      study that showed the third component: the wrong belief that Entamoeba
      histolytica is resistant to metronidazole. Thirty-five individuals infected with
      one or both species of E-histolytica-E. dispar combination were given
      metronidazole at a dose of 250 mg three times daily for 10 days. Stool samples
      taken immediately after the treatment were tested by ENZYMEBA to detect one or
      both species and by a multiplex polymerase chain reaction procedure to determine
      the existing species. The results of these assays revealed that E. histolytica
      infection disappeared in all the cases, therefore, we may conclude that in
      Cienfuegos province and probably in the rest of the country, metronidazol remains
      an effective drug in the treatment of intestinal amebiasis

PMID- 15849936
TI  - [Meningococcal disease in the City of Havana before and after vaccination].
AB  - The development of risk before and after vaccination in the City of Havana
      province was described. Data were collected from epidemiological surveys of all
      cases under 5 years diagnosed with meningococcal disease during pre-vaccination
      period (1983-1984) and post-vaccination period (989,1990 and 1998). They were
      processed by using the Geographic Information System Mapinfo 4.1. During 1983 and
      1984 when there was no vaccinal intervention, high incidence rates in all age
      groups were observed in most of the municipalities of the province. However, in
      1989, the vaccination coverage was extensive and from that moment on, the
      incidence rates decreased and the number of meningitis-free municipalities grew.
      A decrease in frequency of sick children, non-vaccinated children and a very
      small number of children who were not vaccinated as they should have been was
      observed. The benefits of an homogeneous intervention at territorial level in the
      province were proved.

PMID- 15849937
TI  - [Prediction of serotypes of dengue virus by response to IgM antibodies].
AB  - A study of 4 groups of serum samples from Cuba, Costa Rica, Nicaragua and Panama
      was made to determine the serotypes of dengue virus causing epidemics or
      outbreaks by using IgM antibody-capture ELISA(MAC-ELISA). Dengue-IgM diagnostic
      kit was independently used in each of the serotypes and an index value was
      calculated (optical density of the sample/cut-off value) in each case, with which
      two statistical analyses were made: Fisher's variances and Litter significant
      difference (LSD) calculation. Such calculations allowed determining that in Cuba
      and Panama, serotype 2 circulated whereas in Costa Rica, serotype 1 prevailed.
      These were the isolated serotypes in various epidemics. Regarding Nicaragua, very
      heterogeneous responses were obtained, the responsible serotype could not be
      determined since more than two serotypes co-circulated in this country.

PMID- 15849938
TI  - [Entomological observations of a malarial outbreak during an intensive
      surveillance stage in Albaisa, Camaguey].
AB  - An entomological study of the species of Anopheles genus existing in Albaisa, a
      rural area located in Camaguey province, was conducted through catching on human
      bait during an intensive surveillance stage of a malarial outbreak. This study
      was made from November to December 1990. The species Anopheles albimanus
      contributed the highest values of abundance and parity. By evaluating the last
      biotic variable, it will be possible to achieve a reliable assessment of the
      infective capacity of this species whereas the calculation of abundance in An.
      vestitipennis and An. crucians may indicate the epidemiological risk represented
      by these species. Despite the fact that both species were numerically less
      important as compared to An. albimanus, they should be taken into account when
      there are marked population fluctuations. Among the studied anopheles, we
      observed well-differentiated strategies as to abundance-parity and the climatic
      parameters considered for the study.

PMID- 15849939
TI  - [Studies on preadult and adult forms of Anopheles nuneztovari (Diptera:
      Culicidae) Gabaldon 1940 in an originally malarial area in Merida state,
      Venezuela].
AB  - Pre-adult and adult forms of Anopheles nuneztovari were studied and some
      variables of larval breeding from females captured and fed on human bait were
      described. The production of adult anopheles was 46,5% together with sufficient
      number of larvae to carry out any bioassay for studies of antilarval methods. The
      entomological evaluation of adults revealed that Anohpheles nuneztovari
      predominance was 65% over other anopheles existing in the area, with a blood
      sucking activity covering the whole night while peaks are reached near midnight.
      Average bite habit was set at 22,7 mosquitoes per man-hour and the highest
      average of bites (40,4%) occur at 10 to 11pm; the life expectancy at birth of 12
      days and infestivity of 7 days are values compatible with Plasmodium
      transmission. The blood-sucking habit of this species also showed that 56,3% of
      females rest at home before biting whereas 32% of anopheles remained home with
      full stomach after biting, which indicates an important change in this vector's
      behaviour in the studied area.

PMID- 15849940
TI  - [Biolarvicide Bacillus sphaericus-2362(GRISELESF) for the control of malaria in a
      health area of the Republic of Honduras].
AB  - The results of the application of biolarvicide Bacillus sphaericus
      2362(GRISELESF) for the reduction of larval densities of Anopheles albimanus as
      the impact on the epidemiological situation of the disease in health area 2,
      Sanitary Region 1 of the Ministry of Health Care of Honduras. The biolarvicide
      was applied in 1999 in five health units which were the most affected by this
      tropical disease (Ojo del Agua, Villa de San Francisco, San Juan de Flores,
      Moroceli and El Jicarito). The dose used was 10 ml per square meter of effective
      breeding area; larval densities were estimated during biological pre- and post
      treatment phases. The product showed 100 % effectiveness and a lasting effect up
      to four months after treatment in the 11 monitored breeding sites. This
      entomological impact led to a significantly statistical reduction (p < 0,01) of
      annual parasite incidence in 1999 (21,45) as compared with 1998(45,64) in the
      five treated units. It was also observed that this product was harmless to
      Anopheles almimanus larva-eating fish and insects (Coleoptera, Hemiptera and
      Odonata. The satisfactory entomological and epidemiological results in this
      health area allowed recommending this biological method as part of the
      comprehensive programs for the control of malarial vectors in the Republic of
      Honduras.

PMID- 15849941
TI  - [Antimicrobial susceptibility and serotyping of Pseudomonas aeruginosa isolated
      from HIV/AIDS patients].
AB  - Sixty-eight strains from seropositive patients seen at "Pedro Kouri" Tropical
      Medicine Hospital from October 1996 to September 1997 were analyzed in this
      study. Antimicrobial susceptibility tests by the Kirby-Bauer method and antigenic
      study through slide agglutination of the somatic antigen were performed in such
      strains. The most frequent isolated serogroups were 01(27.9%), 011(10%), 06(8.8%)
      and 05(7.3%); twenty-one strains of 68 isolates (30.9%) could not be serotyped.
      All the strains were susceptible to gentamycin and azlocylin; most of isolates
      were susceptible to ceftazidime (n = 66), and ciprofloxacin (n = 62). On the
      other hand, 25 of the 68 isolates (35.7%) showed resistance to cefotaxime. No
      direct relation between antibiotic resistance and serologic results could be
      proved. According to these results, gentamycin is highly effective for treating
      analyzed strains. In the forthcoming years, beta-lactams and quinolones should be
      more rationally used so as to prevent the emergence of multi-resistant strains in
      Cuba.

PMID- 15849942
TI  - [Bacterial etiology of acute respiratory infections in HIV/AIDS patients].
AB  - A total of 63 HIV/AIDS patients with acute respiratory infections admitted to
      "Pedro Kouri" Tropical Medicine Institute's hospital from January to August 1997
      were studied. 545 samples in all were processed: 153 sputa, 150 hemocultures, 110
      pharyngeal exudates, 61 nasal exudates and 63 otic exudates. The correlation of
      the results from the acridine orange technique, Gram staining and culture was
      studied. The most frequent bacterial agents causing acute respiratory infections
      in the group of isolated strains were: Pseudomonas aeruginosa (29.65 %),
      Staphylococcus aureus (27.14%) and Streptococcus penumoniae (9.04%). The
      microorganisms more frequently associated with bacteriemias were: Staphylococcus
      aureus (16.13%), Pseudomonas aeruginosa (12.90%) and Type b Salmonella (12.90%).
      The acridine orange technique was the most effective in presumptive diagnosis of
      bacteriemia with 95 % certainty since it showed a positivity range from 40, 56 to
      50, 56, with a p < 0,05 which is higher than that of the conventional culture and
      the Gram staining.

PMID- 15849943
TI  - [Adolescents and AIDS].
AB  - A cross-sectional descriptive study was made based on surveys which determined
      the level of knowledge on the most frequent risk factors to catch HIV/AIDS;
      general data about HIV; sex behaviors and risk factors for young adults. The
      universe of study was made up of 404 students at 9th, 10th and 11th grades, who
      live in the urban area of Arauquita municipality, Arauca, Colombia. A randomized
      systematic sampling was carried out; 50 % of the students were taken as a sample,
      that is, 202 students. The survey used was an anonymous structured questionnaire
      consisting of 30 multiple choice questions and open numerical exclusion.

PMID- 15849944
TI  - [Surveillance of the lab personnel exposed to HIV and other bloodborne viruses].
AB  - The results of 15 years of surveillance of the laboratory personnel with
      different levels of exposure to HIV and other bloodborne viruses like HCV, HBV
      and HTLV-1 were presented. Various biosafety measures were applied and ELISA was
      used as the main lab technique. 628 serum samples were analyzed for HIV whereas
      354 for the rest of the viruses but no lab-acquired infection was detected. This
      indicates the low incidence of HIV infection in health care workers at risk and
      the great importance of biosafety measures in the prevention and early detection
      of these infections.

PMID- 15849945
TI  - [Isolation of Mycobacterium avium-intracellulare from a hepatic biopsy].
AB  - A 64 years-old patient, who was a farmer suffering from chronic fever for two
      years, loss of weight and acute asthenia, was studied. He was admitted to "Pedro
      Kouri" Tropical Medicine Institute where the studies were conducted and revealed
      a globular sedimentation rate of 116 mm in 2 hours, and anemia of 9,8g%
      hemoglobin. The laparoscopic study indicated hepatic granulomatosis that was
      confirmed by hepatic biopsy in which a sample was taken from the liver to be
      microbiologically and cytologically examined. By microbiological methods, a non
      pigmented slowly-growing strain was isolated, which was classified by
      conventional diagnostic techniques for the non-tuberculous mycobacteria
      classification and the alternative diagnosing technique known as bidimensional
      thin layer chromatography to confirm the previous classification and set the
      mycolic acid patterns. The isolated strain belonged to group III of Rynyon and
      was identified as Mycobacterium avium-intracellulare.

PMID- 15849946
TI  - [Mortality from tuberculosis in Cuba. 1902-1997].
AB  - The behavior of mortality from tuberculosis in Cuba from 1902 to 1997 was
      described. During the xx century, tuberculosis has been studied in various
      stages, but no papers reflecting its behavior in a comprehensive way have been
      published so far. To this end, the notifications of tuberculosis and the
      populations by sex, age and provinces available since 1902 in the archives of the
      National Statistics Division of the Ministry of Public Health were taken into
      consideration. The trend and the percentages of variation of the gross and
      specific rates were analyzed. A descending trend of mortality from tuberculosis
      with rates from 230.9 x 10(5), in 1902, to 0.7, in 1997, was observed. It
      decreased 71.7% between 1902 and 1940, 74% between 1943 and 1959, 85% between
      1960 and 1978, and 0.16% between 1985 to 1991. It increased 40% from 1991 to 1994
      and it decreased 30% from 1994 to 1997. Pulmonary and extrapulmonary tuberculoses
      descended in the same way. They were higher among females until 1940, but from
      1943 on it was observed a predominance in males. The highest rates were observed
      in the group aged 45 and over. They have been insignificant among individuals
      under 15 for the last 30 years. The highest rates were reported in the capital of
      the country. It was concluded that the mortality rates from tuberculosis have
      decreased remarkably during the present century and that it should disappear as a
      health problem in the next 10 years.

PMID- 15849947
TI  - [Diagnosis of coccidia and microspores in specimens of diarrheal feces from Cuban
      HIV seropositive patients: first report of microspores in Cuba].
AB  - The numerous specimens of liquid diarrheas received at the clinical parasitology
      laboratory of "Pedro Kouri" Institute of Tropical Medicine were studied searching
      for the presence of pathogenic agents of Coccidium subclass and of the microspore
      family. The conditions to diagnose microsporidia were created on July 13, 2000,
      and the method was incorporated to the battery of diagnostic techniques used in
      the laboratory. A cut-off was made after 4 months to analyze the positivity
      found. A frequency distribution study was conducted and it was observed that of
      the 170 studied samples, 51 proved to be positive for some protozoon, which
      represents 30% of positivity. The most frequently found species were
      Cryptosporidium parvum and microsporidium. Association of various species in a
      same sample was found in 13.1% of the positive samples. The most frequent
      associations were: Cryptosporidium parvum and Cyclospora cayetanensis,
      Cryptosporidium parvum and microsporidium, and Cyclospora cayetanensis and
      microsporidium, each with 2 patients. Association of 3 different species in a
      same sample was also found. All the individuals in the series were HIV
      seropositive and the most affected had less than 200 TCD4+ lymphocytes/mL. This
      was the first report of microsporidia in feces in Cuba. It was possible after
      applying and interpreting the technique previously described to identify this
      phylum. As there is a trend towards the increase of cases with HIV/AIDS
      infection, it is necessary that the laboratories have the indispendable reagents
      to perform the modified Didier's trichromic staining and that the professionals
      and technicians of the parasitology laboratories of the country be trained in the
      procedures for identifying and recognizing these opportunistic protozoa.

PMID- 15849948
TI  - [Intestinal parasitosis in children admitted to the Pediatric Teaching Hospital
      of Cerro, Havana City, Cuba].
AB  - A study on intestinal parasitism was conducted among 401 children admitted in the
      Pediatric Teaching Hospital of Cerro, from May to June, 1999. To this end, a
      representative, randomized and stratified sample by service was taken. 3 samples
      of feces per child were collected, preserved in formaldehyde, and processed by 3
      parasitological methods. There was an intestinal parasitism prevalence of 15% at
      the hospital and there were no differences between the stratum of children
      admitted in Gastroenterology and the rest of the services as regards commensals
      and parasites in general (p > 0.05); however, commensals predominated in the
      second group (p < 0.01) The intestinal coccidia, Cryptosporidium parvum and
      Cyclospora cayetanensis prevailed in the Gastroenterology service over the rest
      of the services (p < 0.01). The age group over 4 (school children) was the most
      affected, both by protozoa and commensals (p < 0.01), excepting Cryptosporidium
      parvum that affected the infants more (p < 0.05). The analysis of some
      epidemiological antecedents showed that those children eating fruit without
      peeling and washing them, having vegetables withouth washing them first and
      walking barefooted were more prone to infection (RR > 1). A higher frequency of
      infection due to intestinal parasites was found among those living in rural
      areas, drinking well or river water, and defecating in latrines or in the open
      air (RR > 1). These results suggested that in spite of the existing knowledge of
      the epidemiological and risk factors, the intestinal parasites continue affecting
      the child population

PMID- 15849949
TI  - [Detection of lymphoproliferative response in monkeys innoculated with dengue 4
      virus].
AB  - A group of 6 Cynomolgus monkeys was immunized with dengue 4 virus (H247 standard
      strain). 60 days after innoculation the cellular proliferation against the same
      serotype as well as against hetereologous serotypes 1 and 2 was measured. A
      proliferative response predominantly of the specific serotype and some cross
      reactivity were detected. These results showed a behavior of primates similar in
      some extent to that of human beings and mice regarding the specific serotype and
      cross serotype response to dengue virus.

PMID- 15849950
TI  - What percentage of the Cuban HIV-AIDS epidemic is known?
AB  - The data for the Cuban HIV-AIDS epidemic from 1986 to 2000 were presented. With
      the purpose of evaluating the efficiency of the HIV detection system, two methods
      were used to estimate the size of the HIV-infected population, backcalculation
      and a dynamical model. From these models it can be estimated that in the worst
      scenario 75% of the HIV-infected persons are known and in the best case 87% of
      the total number of persons that have been infected with HIV have been detected
      by the National Program. These estimates can be taken as a measure of the
      efficiency of the detection program for HIV-infected persons.

PMID- 15849951
TI  - On the unsual hemorrhagic and necrotic activities caused by the rattlesnake
      (Crotalus durissus cumanensis) in a Venezuelan patient.
AB  - The hemorrhagic, necrotic and edematous effects observed in a 23-year-old patient
      from Lagunetica, Los Teques, state of Miranda, Venezuela, that was bitten by a
      common Venezuelan rattlesnake (Crotalus durissus cumanensi), were described. The
      patient was treated with polyvalente serum, antibiotics and autograft. This
      finding allows to suggest that the poison of some Venezuelan common rattlesnakes
      has a systemic effect on the skeletal muscle and on capillaries that generate
      edema, hemorragic phenomena and necrosis.

PMID- 15849952
TI  - [Lyme disease in Cuba? Report of possible cases].
AB  - Two possible cases of Lyme disease, which has not been reported in Cuba, but
      whose existence has been suspected for some years, are reported. These cases that
      were bitten by ticks and presented signs and symptoms compatible with this
      disease, according to literature, were serologically confirmed by different
      laboratory techniques (indirect immunofluorescence, ELISA and Western Blotting).
      The results suggest the presence of this borreliosis in Cuba.

PMID- 15849953
TI  - Weil's syndrome.
AB  - A case of leptospirosis in an 18-year-old white male was reported. Weil's
      syndrome was characterized by intense jaundice, acute renal failure, skin
      ecchymoses and conjunctival suffusion, in addition to meningitis. The polymerase
      chain reaction for Leptospira was negative, while the titers of the antibody
      microagglutination test against L. grippotyphosa rose higher than fourfold (up to
      1:1,600) in the same blood sample. Patient's treatment consisted of rehydration
      and supportive care of acute renal failure, besides antibiotic therapy.
      Penicillin administration started after 6 days of disease. Patient improved
      without clinical sequelae.

PMID- 15849954
TI  - [Liver abscess and HIV: report of a case].
AB  - The association of a liver abscess of possible amebic etiology with HIV in a
      Cuban patient that worked in the Republic of Ethiopia was described. This is
      important because during the time elapsed since the HIV was described, multiple
      opportunistic infections were reported, some of them capable of giving rise to
      the formation of liver abscesses, but none of them with an amebic etiology. In
      addition, this patient was the first case of liver abscess of possible amebic
      etiology reported in the whole population of HIV (+) patients studied at "Pedro
      Kouri" Institute of Tropical Medicine.

PMID- 15849955
TI  - [Blackwater fever: a case report].
AB  - The first case of blackwater fever was reported in Cuban medical literature. It
      is an uncommon complication of paludism due to Plasmodium falciparum,
      characterized by fever, hemoglobinuria, and kidney failure, with dramatic
      development and high mortality. The patient came from the People's Republic of
      Angola, where he stayed 7 years, with history of various episodes of malaria. He
      was admitted with fever, icterus and thick film test positive for P. falciparum.
      Treatment with quinine was started, but dark red urine and an increase of icterus
      were observed 12 hours later. Treatment with quinine was suspended. Red blood
      cells and platelets were transfused and hemodialysis and plasmapheresis were
      performed. The patient was discharged 2 weeks later asymptomatic and with
      negative thick film test. The pathogeny of this disease was discussed, specially
      kidney failure, making emphasis on the importance of the symptomatic and
      maintenance treatment in the patient's evolution.

PMID- 15849956
TI  - [AIDS and hemophilia in pediatrics: report of a case].
AB  - It is reported the case of a 12-year-old white school boy with diagnosis of
      degree III hemophilia A since he was 2 months old that had received innumerable
      transfusions of cryoprecipitate and several of blood. In 1999, he was diagnosed
      hepatitis C and, at the end of 2000, HIV infection. There was a high possibility
      of having acquired them both by the blood and hemoderivative transfusions
      received. As very low figures of TCD4 lymphocytes (4%) with 54 cells/mm3 were
      corroborated on conducting immunological studies, it was classified as group B-3
      AIDS, according to the classification established by the CDC of Atlanta, in 1994.
      He was indicated antiretroviral treatment with tritherapy (d4T, 3TC and
      Nelfinavir). This case was reported to call the attention of doctors at the time
      of indicating treatment with antivirals or protease-inhibitors to fight AIDS in
      pediatric cases with diagnosis of hemophilia, since some of them may cause
      spontaneous bleeding episodes.

PMID- 15849957
TI  - [Report of Mycobacterium avium-intracellulare associated with kidney
      mycobacteriosis].
AB  - Consecutive samples of urine from a patient presenting radiological images of
      multicystic kidneys were microbiologically analyzed searching the possible
      presence of acid-alcohol resistant bacilli. The patient had already undergone
      complementary tests, which evidenced a kidney failure. As a result, it was
      isolated a slow-growth non pigmented mycobacterial strain corresponding to group
      III of Runyon. It was classified as Mycobacterium avium-intracellulare, according
      to conventional and alternative bacteriological studies, such as the analysis of
      fractions of mycobacterial mycolic acids by thin layer chromatography technique.

PMID- 15849958
TI  - [Historical evolution of Marianao municipality: setting in which the fight
      against tuberculosis developed].
AB  - A research on the fight against tuberculosis in Marianao municipality was made.
      In Cuba, this campaign since its beginning was in the hands of private entities
      with limited resources that were inscrupulously managed. The Marianao
      municipality, established in 1878, had municipal administrations that implemented
      negative policies for the people's interests and propitiated the spreading of
      tuberculosis due to the terrible working and living conditions of the population.
      Since the triumph of the Revolution, in 1959, it was established in Cuba a
      systematic fight against tuberculosis with the introduction of the National
      Control Program that acts in a decentralized way from the municipal level. In
      this municipality, the incidence of tuberculosis has historically been a health
      problem, although at present there is a trend towards the decrease of this
      disease and it occupies the 13th place among the 15 municipalites of the province
      of Havana City.

PMID- 15849959
TI  - [Evaluation of different liquid media for the culture of Gardnerella vaginalis
      and characterization of the protein profile with PAGE-SDS electrophoresis].
AB  - 3 liquid culture media: triptose soya broth supplemented with equine serum (TSB
      es)/without supplement (TSB) and Casman broth (CB) were evaluated under different
      incubation conditions at 10% of CO2 and under aerobic conditions. There were no
      significant differences in the values of optic density for the TSB-es and CB
      media. However, on establishing the protein profile by PAGE-SDS for the evaluated
      conditions, the presence of protein of 14 kDa and the values of optic density
      allowed the selection of the CB medium for the culture of Gardnerella vaginalis.
      The sensitivity to different pH in this medium was studied. pH 7.2 proved to be
      optimum and it was established its growth cynetics. The analysis by PAGE-SDS of
      the complete cells corresponding to different clinical isolates of G. vaginalis
      with biochemical variations made possible to characterize the protein profile in
      this medium and showed similarity between the isolates.

PMID- 15849960
TI  - [In vitro sensitivity of Histoplasma capsulatum var. capsulatum to amphotericin
      B, ketoconazole, itroconazole and fluconazole].
AB  - The minimum inhibitory concentration (MIC) was determined by a micromethod of
      dilution in RPMI-1640 broth in order to know the sensitivity to amphotericin B,
      itraconazole, ketoconazole and fluconazole of 29 strains of Histoplasma
      capsulatum var capsulatum isolated in Cuba. Histoplasmosis is one of the main
      systemic mycosis at the world level and its incidence has increased during the
      last years, associated mainly with HIV infection and to the appareance of new
      epidemic outbreaks in different regions. The results obtained allowed to conclude
      that high values of IMC against fluconazole were found with a geometric mean of
      55.5 ug/mL. For amphotericin B, ketoconazole and itraconazole, all the strains
      were inhibited at low concentrations with geometric means of 0.26, 0.17 and 0.125
      ug/mL, respectively. The development for the first time in Cuba of a method to
      determine the IMC of the main antifungal drugs against H. capsulatum var
      capsulatum will make possible to establish the sensitivity patterns and to detect
      the appearance of resistance, which will contribute to know this important
      mycosis better.

PMID- 15849961
TI  - [Safety and immunogenecity of a vaccine of polyssacharide Vi from Salmonella
      typhi in Cuban youths].
AB  - A randomized, controlled and double-blind study was conducted in young adults
      aged 18-20 aimed at evaluating the reactogenecity and immunogenecity of vaz-TyVi,
      a vaccine of polyssacharide Vi from Salmonella typhi. They were distributed into
      3 groups: immunized with a dose of Vax-TyVi (Finlay Institute), TYPHIM Vi
      (Pasteur-Merieux) or vax-TET (tetanic toxoid). Serum samples were taken before
      and 21 days after immunization. The immunogenecity was evaluated in 323
      volunteers by an indirect ELISA. The seroconversion of those receiving vax-TyVi
      was 81.97% and 65.05 % for TYPHIM Vi. The postvaccine mean geometric titers were
      7.41 U/mL (5.92-9.27 U/mL) and 5.41 U/mL (4.35-6.72 U/mL), respectively. The
      seroconversion with vax-TET was 0%. The reactogenecity of both polysaccharide
      vaccines was low. It was concluded that the immunogenecity of vax-TyVi was not
      lower than that of TYPHIM Vi and that its reactogenecity was similar.

PMID- 15849962
TI  - [Evaluation of different methods of utilization of sugars in Neisseria
      gonorrhoeae].
AB  - 5 methods of utilization of sugars were evaluated in 25 strains previously
      identified as N. gonorrhoeae: CTA agar, modified CTA agar, gelatin starch agar,
      Mueller Hinton agar plus bromotimol blue and rapid method. 100% of the strains of
      N. gonorrhoeae were identified by the CTA and rapid methods, whereas 96% were
      identified by the modified CTA and gelatin starch agar methods. No strain of
      gonoccocus was identified by the Mueller Hinton agar method plus bromotimol blue.
      The cystine tripticase agar medium (CTA) is the elective method to confirm the
      isolates of Neisseria gonorrhoeae. As it is mainly made by U.S. companies, it is
      difficult for Cuba to acquire it. The gelatin-starch agar method and the rapid
      method are useful alternative of the CTA medium, so their use is proposed in this
      paper.

PMID- 15849964
TI  - [Importance of the microbiological confirmation in an outbreak of human
      leptospirosis in the city of Villa Clara].
AB  - A multidisciplinary group was created to confirm the existance of human
      leptospirosis in the province of Villa Clara where by the end of June, 1977,
      there was a considerable increase of febrile cases with symptoms and signs
      consistent with diseases such as hemorrhagic dengue and human leptospirosis. The
      National Laboratory of Reference of Leptospires from "Pedro Kouri" Institute,
      organized a set of direct and indirect diagnostic techniques as a working
      strategy that would serve to confirm this health problem. As a final result, it
      was observed that the Ballum, Pomona, Canicola and icterohaemorrhagiae serogroups
      showed the highest percentage of appearance among the studied cases. A total of 7
      cases had active infection, since they were positives by the passive
      hemoagglutination method. The four severe cases studied by passive
      hemoagglutination and microagglutination were positive. Sera from the 3 patients
      with febrile syndrome of unknown ethiology were negative by these 2 techniques.
      The 3 samples obtained from the autopsy of a dead were positive by direct exam in
      dark field and staining of immunoperoxidase. The monosera of the dead subjects
      were highly reactive by passive hemagglutination (titers from 1-10 and up to 1
      640). 2 hemocultures were typified as Ballum; 2 urines and 1 hemoculture were
      positive by polymerase chain reaction. In this way, a fast answer was given to
      the health public authorities from the Viceministry of Hygiene and Epidemiology
      of Cuba on confirming microbiologically the existance of the disease. lt was
      sugggested to administer the Cuban vax SPIRAL vaccine in the affected area.

PMID- 15849963
TI  - [Detection of antirabic antibodies in personnel at risk through the use of the
      neutralization technique by reducing the number of plaques].
AB  - The neutralization technique by reducing the number of plaques (NRNP) for
      detecting antirabic antibodies in personnel at risk was used. Serum samples from
      individuals at high risk and from persons with vaccination antecedents and
      without them were studied. The neutralization technique was compared with the
      biological technique in mouses and as a result of the study it was obtained a
      concordance of 100%. It was found that sex does not influence on the response of
      the antibodies to this virus, although the direct contact and the number of times
      that the individual has received the vaccine act positively on the immune
      response. The introduction of this technique in the laboratory allows to have a
      useful tool for the follow-up of the personnel receiving the vaccine before and
      after being exposed to the rabies virus.

PMID- 15849965
TI  - [Lethal effect of Cuban Myrtaceae on Aedes aegypti (Diptera Cuilicidae)].
AB  - The biological activity of the essential foliar oils from 2 Cuban endemic
      Myrtaceae: Eugenia melanadenia and Psidium rotundatum on A. aegypti larvae was
      evaluated for the first time at the laboratory level. The probit-log analysis of
      the results showed the larvicidal effect of both oils with values of CL50 =
      0.0085% and CL95 = 0.0104% for E. melanadenia and CL50 = 0.0063% and CL95 =
      0.0071% for O. rotundatum. Besides, the diagnostic concentration for both
      essential oils are given and the possible implications of these findings on field
      populations of A. aegypti are suggessted.

PMID- 15849966
TI  - [Cross resistance to pyrethroids in Aedes aegypti from Cuba induced by the
      selection with organophosphate malathion].
AB  - A strain from Aedes aegypti (L) collected in the municipality of Santiago de Cuba
      with low levels of resistance to malathion (1.79x) was subjected to selection
      pressure aimed at evaluating the evolution of the resistance to this
      organophosphate and its usefulness for control. After 5 generations of selection
      (SAN-F5) with malathion, it was not possible to increase the resistance and it
      was obtained a value of resistance factor (FR50) of 2.22x. None or little cross
      resistance to the following organophosphate insecticides was observed: fenthion,
      temephos and fenitrotion; however, it was found an elevated cross resistance to
      deltamethrin pyrethroid, with a value of 287.5x in the third generation of
      selection. It was also observed cross resistance to other pyrethroids (lambda
      cyhalothrin, cypermethrin and ciflutrine). The mechansim of elevated esterases
      did not generate resistance to pyrethroids, which was corroborated through
      inhibition gel studies and through the calculation of the frequency in
      microtitering plaques. Nevertheless, there was an increase in the frequency of
      the glutathione-s-transferase mechanism from 0.049 in Santiago de Cuba to 0.42 in
      SAN-F5, which may be associated with the resistance to pyrethroids. The cross
      resistance to pyrethroids, mainly to deltamethrin, resulting from the selection
      with malathion may limit the use of these insecticides in the control unless a
      good strategy for their use is laid down.

PMID- 15849967
TI  - [The most frequent bacterial isolates in biological samples from HIV-infected
      patients].
AB  - A descriptive and retrospective study was conducted aimed at knowing the behavior
      and the frequency of the bacterial isolations most frequently found in different
      biological samples (sputum, blood and urine) from patients with HIV/AIDS
      diagnosis that were seen at the Outpatient Department or that were admitted at
      the Hospital of "Pedro Kouri" Institute of Tropical Medicine from 1997 to 2001.
      It was observed that most of the isolations were obtained from sputum samples and
      that Pseudomonas aeuroginosa was the most isolated microorganism in all samples.
      Pseudomonas aeuroginosa proved to be the most isolated microorganism in sputum
      with 28.5%. The bacteria most commonly isolated in blood was Staphylococcus
      epidermidis with 48.5%. The uropathogenic microorganism most found in urine was
      Escherichia coli with 43.5%.

PMID- 15849968
TI  - [Effects of VIMANG on various markers of HIV-1 progression in Cuban patients].
AB  - 68 patients divided into 2 groups were studied, one that received VIMANG during 6
      months and another that was administered placebo. Titers of anti-p24 antibodies
      and concentration of antigen p24 were measured at 0 and 6 months. The differences
      found in the behavior of the titers of the antibodies between both groups were
      not significant, although the TPG were maintained in the group receiving VIMANG.
      In the placebo group, 2 patients elevated the antigen concentration and 2 were
      positive for this marker, whereas in the study group the Ag disappeared in a
      patient who became positive but with values 3 and 4 times lower than in the 2
      patients of the control group, where it increased.

PMID- 15849969
TI  - [Pigmentation of Cryptococcus neoformans strains on sunflower seed agar].
AB  - The production of melanin on a medium of sunflower seeds extract agar from 86
      strains of Cryptococcus neoformans belonging to the Mycology Laboratory of "Pedro
      Kouri" Institute of Tropical Medicine was determined. 54.7% of them produced
      colonies with dark brown pigment, 5.8% a light pigment and 37.2% an intermediate
      tonality. A fourth group was created for those strains with a true pigment
      (2.3%). This paper is an important contribution to attain a better
      characterization of the strains from the collection of the institution and serves
      as a basis to further studies of pathogenicity and susceptibility.

PMID- 15849970
TI  - [Importance of medical education in the diagnosis of toxoplasmosis in Cuba].
AB  - The results of the National Toxoplasmosis Reference Laboratory during 1999 and
      2000 were processed and the evaluations on this topic were simultaneously
      analyzed among 51 professionals that attended the First National Workshop held at
      "Pedro Kouri" Institute of Tropical Medicine at that time. Of 3 672 orders, 3 171
      (86.3%) did not have the reason for serology, 36.1% had no place of origin and
      only 301 cases (8.1%) were indicated the matched serum. On analyzing the main
      causes leading to make this test, 13.5% corresponded to repeated abortions, which
      is not accepted at present as a clinical manifestation in the course of the
      disease. Coincidentally, when some professionals were evaluated through a survey
      about the basic aspects related to this parasitosis, only 31.3% were able to
      obtain satisfactory marks. Most of the mistakes were observed in the
      interpretation of the laboratory results.

PMID- 15849971
TI  - [Pathogenic effect of the parasite nematode Strelkovimermmis spiculatus (Nematoda
      Mermithidae) in larvae of mosquito Culex quinquesfasciatus (Diptera Culicidae)
      under laboratory conditions in Cuba].
AB  - The infective capacity of Strelkovimermis spiculatus Poinar and Camino, 1986, was
      evaluated under laboratory conditions for the first time in Cuba in order to
      introduce it as a new agent of biological control of mosquitoes of medical and
      epidemiological importance. The second stage larvae of Culex quinquefasciatus
      Say, 1823, were used and exposed to the infective juvenile parasites at different
      doses. It was observed a rise in the mean values of infestation and in the
      mortality percentage with the dose increase. Culex quinquefasciatus Say proved to
      be a good host and a dose of 7:1 will be optimum to attain high percentages of
      mortality and to obtain this parasite massively for its further evaluation under
      field conditions.

PMID- 15849972
TI  - [Disseminated mycobacteriosis associated with Mycobacterium avium-intracellular
      (MAI) complex in HIV infected patients].
AB  - Different types of samples from a 27-year-old female patient who was diagnosed
      AIDS after presenting an acute respiratory picture caused by Pneumocistis
      carinii, in 1997, were studied. From that moment on, the patient continued having
      respiratory pictures repeatedly, until she was admitted at "Pedro Kouri"
      Institute of Tropical Medicine with a chronic diarrheical picture, significant
      loss of weight and extreme anorexia, together with a constant wet cough, fever,
      etc. The necessary complementary tests were made and a hyperergic Mantoux and
      very low levels of CD4 cells (under 200 cells/m3) outstood. Microbiological
      studies were also conducted with samples from sputum, hemocultures and
      cerebrospinal fluid to discard the presence of acid-alcohol resistant bacilli
      (AARB). As a result of these studies, the repeated isolation was obtained in all
      types of worked samples from a slow-growth, creamy and non pigmented strain
      corresponding to Runyon's group III, which was classified as from the
      Mycobacterium avium-intracellulare complex. The patient was treated with
      antibacillary drugs without results, since she dies 4 weeks later due to the
      total dissemination of this infection. It should be stressed that it is the first
      case reported and microbiologically diagnosed of a generalized mycobacteriosis in
      a HIV positive patient due to Mycobacterium avium-intracellulare.

PMID- 15849973
TI  - Simvastatin over the counter.
AB  - In July 2004, simvastatin 10mg was reclassified in the UK from a Prescription
      only medicine (PoM) to a Pharmacy (P) medicine and launched as Zocor Heart-Pro
      (Johnson & Johnson. MSD Consumer Pharmaceuticals). It is the first statin in the
      world to be sold without prescription. Zocor Heart-Pro is licensed to reduce the
      risk of a first major coronary heart disease (CHD) event in people likely to be
      at "moderate risk" of such problems. Here we review the rationale and process for
      reclassifying simvastatin 10mg as an over-the-counter product.

PMID- 15849974
TI  - Drug treatments for bipolar disorder: 1--Acute manic or depressive episodes.
AB  - Bipolar disorder is a severe, chronic mental illness characterised by repeated
      episodes of mania or hypomania, depression or mixed affective states. Depending
      on the clinical context, treatment may involve drugs, psychological therapies,
      social interventions and/or electroconvulsive therapy (ECT). Here we concentrate
      on the role of drug treatments for acute manic or depressive episodes in adults
      with bipolar disorder. A second article will consider their role as maintenance
      and preventive therapy, and in special situations such as pregnancy.

PMID- 15849975
TI  - [Evidence-based clinical decision making].

PMID- 15849977
TI  - [Didactic concept for the continuing education event].

PMID- 15849976
TI  - [Hyperuricemia/gout. Main symptoms of arthropathy. Severe acute joint pain,
      redness, inflammation].

PMID- 15849978
TI  - [The efficacy of a treatment: absolute and relative risk, number of patients to
      be treated].

PMID- 15849979
TI  - [Fundamentals for interpreting diagnostic tests].

PMID- 15849980
TI  - [How to evaluate a patient's prognosis? Or: on the meaning of prognostic
      scoring].

PMID- 15849981
TI  - [Plant therapy in diabetes?].

PMID- 15849982
TI  - [Apert syndrome: a reported observation].
AB  - Apert syndrome is a type of acrocephalosyndactylia that belongs to the group of
      craniofacial synostoses. It is characterised by craniofacial dysmorphia and
      syndactyly of hands and feet. It is an uncommon affection that is often
      transmitted through an autosomal dominant mode, but sporadic cases are frequent.
      We report the case of a 2 months old baby brought by his parents to the
      paediatric emergencies for respiratory distress occurring within the framework of
      a polymalformative syndrome. The examination showed brachycephaly, bilateral
      exorbitism, syndactyly of the hands and feet and an anal fistula.
      Echocardiographic examination showed a cardiovascular malformation
      (interventricular communication), the whole suggestive of Apert syndrome. The
      child was admitted in intensive care during five days. He died following a
      respiratory infection. Through this observation the authors illustrate the
      clinical and evolutionary aspects as well as the therapeutic difficulties of this
      affection.

PMID- 15849983
TI  - [Isolated hypertrophy of the superior oblique muscle in Basedow disease].
AB  - INTRODUCTION: Proptosis is the most common feature of Graves' ophthalmopathy. We
      report an exceptional case of proptosis in relation with an isolated enlargement
      of the superior oblique muscle in Graves' ophthalmopathy. OBSERVATION: After
      ocular contusion a 37 years old man presented a progressive right exophthalmos.
      On examination there was an unilateral proptosis with dilated conjunctival
      vessels, without any clinical signs of inflammation and no decreased vision.
      Ocular movements were full. On general examination signs of hyperthyroidism were
      present. CT-scan showed a superior oblique muscle enlargement with enlarged
      superior ophthalmic vein. Cerebral angiography excluded the diagnosis of a
      carotid-cavernous fistula. Dosage of thyroid hormone revealed hyperthyroidism.
      DISCUSSION: This case has a double interest: --Diagnostic: a CT-scan picture
      mimicking a carotido-cavernous fistula in this particular clinical context
      (history of ocular trauma, enlarged conjunctival vessels). --Isolated enlargement
      of superior oblique muscle in Graves' disease, which is exceptional in the
      literature.

PMID- 15849984
TI  - [Important bilateral corneal astigmatism in a case of ocular ochronosis].
AB  - Ochronosis or alkaptonuria is a rare, autosomal recessive metabolic disease where
      the enzyme homogentisic acid 1,2-dioxygenase is missing. This enzyme is necessary
      in the oxidation of phenylalanine and tyrosine. As a result of this defect
      homogentisic acid, which is normally produced during the metabolism of the two
      amino-acids, cannot be further metabolized and therefore accumulates in the
      serum. It is massively excreted in the urine and as it is oxidized, the urine
      turns dark, a feature termed alkaptonuria. Tissue pigmentation called ochronosis
      is due to the presence and the chemical binding in the connective tissue of
      oxidized and polymerised products of homogentisic acid. The most important
      complications of alkaptonuric ochronosis as arthropathy are related to deposition
      of ochronotic pigment in the affected organs. In ocular ochronosis, the pigment
      is found in the sclera, conjunctiva, and limbic cornea. Vision is usually not
      impaired. We report the case of a man aged 73 years, with ochronosis, who
      developped a marked, late-onset bilateral astigmatism, related to this sclero
      limbic ochronotic pigment. The clinical evolution, the result of histological
      examination and the physiopathology of this astigmatism are discussed.

PMID- 15849985
TI  - [Cysts of the iris in an infant. 2 case reports].
AB  - Iris cysts are rare in children. They might be primary or secondary. Their
      treatment depends on their type and clinical evolution. The purpose of our study
      is to discuss the etiologies and therapeutic modalities of iris cysts.

PMID- 15849986
TI  - Clinical symptoms and complications of pars planitis in childhood.
AB  - Pars planitis is the idiopathic form of intermediate uveitis; it most commonly
      affects persons between 5 and 40 years of age. In childhood, the disease is
      largely asymptomatic until in a well advanced stage with markedly reduced vision.
      Lack of early diagnosis and treatment may lead to permanent visual loss and
      amblyopia. AIM: To report on the clinical symptoms, complications, treatment and
      visual outcome of pars planitis in childhood. MATERIALS AND METHODS: Ten patients
      (8 boys and 2 girls) all younger than 16 years were diagnosed with and treated
      for pars planitis at our clinic between January 1993 and August 2004.

PMID- 15849987
TI  - Bilateral Coats' disease with unusual presentation--a case report.
AB  - Coats' disease is a well-known ocular disorder, characterized by idiopathic
      retinal telangiectasia, retinal exudation and retinal detachment. We report on a
      boy who first presented at the age of 2 years with Coats' disease and secondary
      neovascular glaucoma. The differential diagnosis with retinoblastoma could not be
      made clinically or with the help of imaging studies, such as ultrasonography or
      computed tomography scanning (CT-scan). The right eye was consequently enucleated
      for diagnostic and therapeutical purposes. Histopathologic examination confirmed
      the diagnosis of Coats' disease. Five years later the same boy consulted again
      with profound visual loss in his only functional left eye. Fundoscopy revealed
      lesions typical for Coats' disease. Coats' disease can present in very different
      ways and bilateral disease is possible, even after several years.

PMID- 15849988
TI  - [Rosary-like abnormality of retinal veins:report of a case].
AB  - Inherited retinal venous beading is a rare autosomal dominant disorder with
      variable expressivity. It is characterized by irregular, segmented beading of the
      retinal veins. Some patients have arteriolar tortuosity. The conjunctiva can be
      affected by saccular vascular changes. Episodes of acute retinal vascular
      decompensation are also described. Low to normal leucocyte and neutrophil counts
      may be an extraocular associated condition. We describe the isolated case of a
      woman presenting retinal venous beading and conjunctival vascular aneurysms. She
      has no systemic anomaly and her family members examined are unaffected.

PMID- 15849990
TI  - Wound healing after glaucoma surgery: how to manage it?
AB  - Agents such as the antimetabolites 5-fluorouracil (5FU) and mitomycin-C (MMC)
      have revolutionised glaucoma surgery in patients with a high risk of surgical
      failure. However, vision threatening complications can be associated with the use
      of these agents. Changes in antimetabolites application during and after the
      surgery can increase the safety and reduce the complications while maintaining
      effectiveness.

PMID- 15849989
TI  - Clinical and genetic significance of unilateral Lisch nodules.
AB  - PURPOSE: Bilateral Lisch nodules are highly characteristic for neurofibromatosis
      type 1 (NF1). We wished to study the clinical and genetic implications of
      unilateral Lisch nodules. METHODS: Retrospective study of the clinical data of 59
      patients who received genetic counselling for neurofibromatosis type 1 (NF1) or
      type 2 (NF2) and were examined at the department of ophthalmology. RESULTS:
      Unilateral Lisch nodules were observed in 4 cases: one child with NF1 initially
      presented unilateral Lisch nodules but developed bilateral Lisch nodules by the
      age of 9. In 2 cases segmental NF1 was the most probable diagnosis and in one
      case isolated Lisch nodules were observed. Of the 35 NF1 patients 28 ultimately
      developed bilateral Lisch nodules. Seven NF1 patients did not demonstrate the
      nodules. At follow-up no Lisch nodules were detected in 2 neurofibromatosis type
      2 patients, in 4 patients in whom the diagnosis of NF1 remained doubtful and in
      15 patients without NF1. CONCLUSION: Because isolated Lisch nodules are very
      rare, their presence warrants a thorough patient history and clinical examination
      to either confirm or exclude generalised or segmental neurofibromatosis type 1.

PMID- 15849991
TI  - [Vitreo-retinal pediatric surgery: epidemiologic factors, etiology and
      prognosis].
AB  - The features of pediatric vitreoretinal surgery are different from those of the
      adult population. In order to identify those differences, our retrospective
      study, dealing with a consecutive series of 2230 patients who underwent
      vitreoretinal surgery, analyzes several parameters for the 43 young patients
      (under 19 years old) (2%). Two main results can be withdrawn from the study.
      First, trauma is a major cause of vitreoretinal surgery in children (30% of the
      cases), proportionally much more frequent than in adults. Second, patient's age
      is the only factor that significantly influences the surgical prognosis, with a
      success rate of 35% under the age of 10 years, and 73% above this age (p < 0.05).
      We conclude that pediatric vitreoretinal surgery has a more guarded prognosis
      compared to the one performed in the adult population.

PMID- 15849992
TI  - Interactions of peptide mimics of hyaluronic acid with the receptor for
      hyaluronan mediated motility (RHAMM).
AB  - Using the hyaluronic acid (HA) binding region of the receptor for hyaluronan
      mediated motility (RHAMM) as a model, a molecular perspective for peptide mimicry
      of the natural ligand was established by comparing the interaction sites of HA
      and unnatural peptide-ligands to RHAMM. This was accomplished by obtaining a
      series of octapeptide-ligands through screening experiments that bound to the HA
      binding domains of RHAMM (amino acids 517-576) and could be displaced by HA.
      These molecules were computationally docked onto a three-dimensional NMR based
      model of RHAMM. The NMR model showed that RHAMM(517-576) was a set of three
      helices, two of which contained the HA binding domains (HABDs) flanking a central
      groove. The structure was stabilized by hydrophobic interactions from four pairs
      of Val and Ile side chains extending into the groove. The presence of solvent
      exposed, positively charged side chains spaced 11 A apart matched the spacing of
      negative charges on HA. Docking experiments using flexible natural and artificial
      ligands demonstrated that HA and peptide-mimetics preferentially bound to the
      second helix that contains HABD-2. Three salt bridges between HA carboxylates and
      Lys548, Lys553 and Lys560 and two hydrophobic interactions involving Val538 and
      Val559 were predicted to stabilize the RHAMM-HA complex. The high affinity
      peptides and HA utilized the same charged residues, with additional contacts to
      other basic residues. However, hydrophobic contacts do not contribute to affinity
      for peptide ligand-RHAMM complexes. These results offer insight into how
      selectivity is achieved in the binding of HA to RHAMM, and how peptide
      competitors may compete for binding with HA on a single hyaladherin.

PMID- 15849994
TI  - Unsupervised guided docking of covalently bound ligands.
AB  - An approach for docking covalently bound ligands in protein enzymes or receptors
      was implemented in MacDOCK, a similarity-driven docking program based on DOCK
      4.0. This approach was tested with a small number of covalent ligand-protein
      structures, using both native and non-native protein structures. In all cases,
      MacDOCK was able to generate orientations consistent with the known covalent
      binding mode of these complexes, with a performance similar to that of other
      docking programs. This method was also applied to search for known covalent
      thrombin inhibitors in a medium-sized molecular database (ca. 11,000 compounds).
      Detection of functional groups suitable for covalent docking was carried out
      automatically. A significant enrichment in known active molecules in the first 5%
      of the database was obtained, showing that MacDOCK can be used efficiently for
      the virtual screening of covalently bound ligands.

PMID- 15849993
TI  - TOMOCOMD-CARDD, a novel approach for computer-aided 'rational' drug design: I.
      Theoretical and experimental assessment of a promising method for computational
      screening and in silico design of new anthelmintic compounds.
AB  - In this work, the TOMOCOMD-CARDD approach has been applied to estimate the
      anthelmintic activity. Total and local (both atom and atom-type) quadratic
      indices and linear discriminant analysis were used to obtain a quantitative model
      that discriminates between anthelmintic and non-anthelmintic drug-like compounds.
      The obtained model correctly classified 90.37% of compounds in the training set.
      External validation processes to assess the robustness and predictive power of
      the obtained model were carried out. The QSAR model correctly classified 88.18%
      of compounds in this external prediction set. A second model was performed to
      outline some conclusions about the possible modes of action of anthelmintic
      drugs. This model permits the correct classification of 94.52% of compounds in
      the training set, and 80.00% of good global classification in the external
      prediction set. After that, the developed model was used in virtual in silico
      screening and several compounds from the Merck Index, Negwer's handbook and
      Goodman and Gilman were identified by models as anthelmintic. Finally, the
      experimental assay of one organic chemical (G-1) by an in vivo test coincides
      fairly well (100%) with model predictions. These results suggest that the
      proposed method will be a good tool for studying the biological properties of
      drug candidates during the early state of the drug-development process.

PMID- 15849996
TI  - Malignant peritoneal mesothelioma.
AB  - BACKGROUND: The clinical characteristics of malignant peritoneal mesothelioma are
      not fully known, and it appears as a variable entity with different types of
      clinical presentation and with a difficult diagnosis. PATIENTS: Fifteen patients
      with malignant peritoneal mesothelioma were analyzed for asbestos exposure,
      clinical presentation, thrombocytosis, X-rays and echotomographic findings,
      peritoneal fluid cytology, surgical investigations, diagnosis in vita, therapy,
      cause of death, diagnosis time, and survival time. RESULTS: Asbestos exposure was
      present in 12 men. Abdominal pain, ascites, abdominal mass, weight loss and fever
      were the most common presentation symptoms. In 5 patients, the disease presented
      as a surgical emergency. Assembling the presenting symptoms, malignant peritoneal
      mesothelioma was subdivided in 3 types: classical (6 cases), surgical (5 cases)
      and medical (4 cases). Thrombocytosis was present in 11 cases. Peritoneal fluid
      cytology was positive for neoplastic mesothelial cells in 8 of 10 cases.
      Laparotomy (5 patients) and laparoscopy (7 cases) were diagnostic in all cases.
      Diagnosis in vita was malignant peritoneal mesothelioma for 13 patients,
      peritoneal carcinomatosis for 1, with only 1 autopsy diagnosis. Seven patients
      were treated with chemotherapy, showing a progression of the disease. Mean
      symptoms-to-diagnosis time was 122 days (4-410), and mean symptoms-to-survival
      time was 345 days (45-1510). CONCLUSIONS: Malignant peritoneal mesothelioma is a
      very unusual disease characterized by a difficult diagnosis, a rapid evolution, a
      poor response to therapy, and a very high prevalence of thrombocytosis. A new
      clinical classification into three types (classical, surgical and medical) may be
      useful for a correct diagnosis. The early diagnosis of malignant peritoneal
      mesothelioma remains an important open question.

PMID- 15849997
TI  - Incidence, mortality and survival trends of cutaneous melanoma in Umbria, Italy.
      1978-82 and 1994-98.
AB  - Many studies have reported increasing incidence rates of cutaneous melanoma
      during the last 30-40 years; the highest have been observed in Australia and New
      Zealand (27.9/100,000 among males and 25.0 among females) and in North America
      (10.9/100,000 among males and 7.7 among females). In Italy, from 1994-1998, in
      the areas covered by cancer registries (23% of Italian population), the incidence
      rate for males was 8.5 and for females, 1.9/100,000. The aim of the present study
      was to describe incidence, mortality and survival from cutaneous melanoma in the
      Umbrian population during the periods 1978-1982 and 1994-1998.

PMID- 15849998
TI  - Statistical interaction in the survival analysis of early breast cancer using
      registry data: role of breast conserving surgery and radiotherapy.
AB  - PURPOSE: To identify subgroup effects that might influence the survival results
      of postoperative radiotherapy. PATIENTS AND METHODS: Women selected from the
      Surveillance, Epidemiology, and End Results database, aged 40-69 years, with non
      metastasized T1-T2 breast carcinoma, in whom axillary lymph node dissection was
      performed. Subgroup analyses were performed using proportional hazards models
      with interactions. Joint significance of subgroups was evaluated with the Wald
      test. Event was death from any cause. RESULTS: Statistically significant
      interactions were found between type of surgery (breast-conserving [BCS] or
      mastectomy [ME]), radiotherapy [RT], T stage, and extent of nodal involvement,
      but not between treatments and nodal examination. For each treatment combination,
      ME-no RT, ME+RT, BCS-no RT, BCS+RT, the mortality hazard ratios were
      respectively: 1, 1.12, 1.11, 0.78 in T1, 0-3 positive nodes; 2.45, 2.77, 2.71,
      1.92 in T2, 4+ nodes; 1.31, 1.38, 1.33, 1.19 in T2, 0-3+ nodes; and 3.41, 2.79,
      3.44, 2.40 in T2, 4+ nodes. The corresponding joint tests showed: in the absence
      of radiotherapy, no significant survival disadvantage for breast-conserving
      surgery vs mastectomy; with radiotherapy, significant survival advantage for
      breast-conserving surgery irrespective of stage and for mastectomy in T2, 4+
      nodes. For mastectomy in less advanced stages receiving radiotherapy, excess
      breast cancer deaths suggested undocumented adverse selection. The corresponding
      result was considered inconclusive. CONCLUSIONS: The analyses found subgroup
      effects that should be taken into account to interpret treatment results in
      breast cancer.

PMID- 15849995
TI  - Subunit rotation models activation of serotonin 5-HT3AB receptors by agonists.
AB  - The N-terminal extracellular regions of heterooligomeric 3AB-type human 5
      hydroxytryptamine receptors (5-HT3ABR) were modelled based on the crystal
      structure of snail acetylcholine binding protein AChBP. Stepwise rotation of
      subunit A by 5 degrees was performed between -10 degrees and 15 degrees to mimic
      agonist binding and receptor activation. Anticlockwise rotation reduced the size
      of the binding cavity in interface AB and reorganised the network of hydrogen
      bonds along the interface. AB subunit dimers with different rotations were
      applied for docking of ligands with different efficacies: 5-HT, m
      chlorophenylbiguanide, SR 57227, quinolinyl piperazine and lerisetron
      derivatives. All ligands were docked into the dimer with -10 degrees rotation
      representing ligand-free, open binding cavities similarly, without
      pharmacological discrimination. Their ammonium ions were in hydrogen bonding
      distance to the backbone carbonyl of W183. Anticlockwise rotation and contraction
      of the binding cavity led to distinctive docking interactions of agonists with
      E129 and cation-pi interactions of their ammonium ions. Side chains of several
      further amino acids participating in docking (Y143, Y153, Y234 and E236) are in
      agreement with the effects of point mutations in the binding loops. Our model
      postulates that 5-HT binds to W183 in a hydrophobic cleft as well as to E236 in a
      hydrophilic vestibule. Then it elicits anticlockwise rotation to draw in loop C
      via pi-cation-pi interactions of its ammonium ion with W183 and Y234. Finally,
      closure of the binding cavity might end in rebinding of 5-HT to E129 in the
      hydrophilic vestibule.

PMID- 15849999
TI  - Epirubicin and gemcitabine as first-line treatment in malignant pleural
      mesothelioma.
AB  - Malignant pleural mesothelioma represents a rare disease, for which chemotherapy
      actually remains unsatisfactory. From August 1998 to November 2001, 28 chemo
      radio-immunonaive patients were consecutively enrolled in the trial: 22/6
      males/females; median age 63 years (range, 45-79); median ECOG PS 1 (range, 0-2).
      They were treated with epirubicin (100 mg/m2 iv on day 1) plus gemcitabine (1000
      mg/m2 iv on days 1 and 8) every 4 weeks for 6 cycles. Patients who responded to
      chemotherapy (n = 6) were subsequently treated with interleukin-2 (4,500,000 IU)
      subcutaneously every other day, until progression. A total of 124 epirubicin
      gemcitabine cycles were administered (median, 6/patient; range, 2-6). Twenty-six
      patients were evaluated for toxicity. According to WHO criteria, we observed
      grade III-IV hematological and gastrointestinal toxicity respectively in 3
      patients (11%) and 1 patient (3%). No red cell transfusions were required and no
      toxic deaths occurred. Two patients (8%) could not be evaluated for response (no
      therapy performed). According to WHO criteria, the final responses were: partial
      in 4 patients (14%), stable disease in 19 patients (69%), and progression in 3
      patients (10%). In 26 patients, the median survival was 55 weeks (range, 7-222)
      and median time to progression 30 weeks (range, 4-156). At the time of this
      writing, no patient is alive. The 1-year survival was 32%, 2-year survival 11%,
      and 4% at 3 and 4 years. All patients were at stage III, and time to progression
      was 58 weeks and survival 63.5 weeks, without any toxicity. This multi-center
      phase II clinical trial showed that epirubicin plus gemcitabine, as a first-line
      treatment in malignant pleural mesothelioma, has promising activity with a good
      tolerability profile and symptom palliation. The role of interleukin-2 in
      maintenance therapy for malignant pleural mesothelioma is encouraging and
      requires further study.

PMID- 15850000
TI  - Hepatic arterial infusion chemotherapy in sarcoma liver metastases: a report of 6
      cases.
AB  - AIMS AND BACKGROUND: Liver metastases in patients with sarcoma are rare and
      associated with a poor prognosis. The experience with liver-directed therapies,
      eg hepatic arterial infusion, in these patients is limited. METHODS: Six patients
      with sarcoma metastatic to the liver (4 patients with gastrointestinal stromal
      tumors and 2 patients with leiomyosarcoma) were treated by hepatic arterial
      infusion in our center over a 12-year period. Since the experience was limited, a
      pooled analysis of reports with data on survival of 22 individual patients was
      performed. RESULTS: None of the 5 assessable patients responded to the therapy,
      and liver metastases progressed in all patients. The median survival was 20
      months. In the pooled analysis, partial response was observed in 10 of 21
      assessable patients (48%) and median survival was 20 months. The survival was
      significantly longer in responding patients compared to nonresponders (35 vs 14
      months; logrank test, P = 0.009). CONCLUSIONS: Hepatic arterial infusion has
      little efficacy in the treatment of sarcoma metastatic to the liver. More
      promising results have been reported for chemoembolization. The survival of
      responding patients seems to be better compared to non-responders.

PMID- 15850001
TI  - Primary pulmonary lymphoma: diagnosis and follow-up of 6 cases and review of an
      uncommon entity.
AB  - AIMS AND BACKGROUND: Primary pulmonary lymphoma is an uncommon disease with a
      poorly defined management. We reviewed and followed the cases of primary
      pulmonary lymphoma in our institution to gather an estimation of this entity in
      our population. DESIGN AND METHODS: We reviewed the records of all patients with
      biopsy-proven lymphoma of the lung. The main diagnostic criterion for primary
      pulmonary lymphoma was the absence of extrapulmonary involvement. RESULTS: We
      identified 6 cases of primary pulmonary lymphoma among 33 patients with biopsy
      proven lymphoma of the lung evaluated in our center in a 12-year period. A
      radiological abnormality in an asymptomatic patient was the most common clinical
      presentation. Four cases were low-grade and two cases high-grade non-Hodgkin PPL.
      Histopathologic analyses of lung specimens obtained by transbronchial biopsy were
      sufficient for a diagnosis in 5 of the 6 cases and avoided invasive surgical
      maneuvers. Most patients followed an indolent course, but with a tendency to
      relapse. CONCLUSIONS: Although clinical management of this entity is undefined,
      we feel bronchoscopic study, which is less aggressive than surgery, may be an
      adequate procedure for a diagnosis. Mono-chemotherapy using alkylating agents and
      careful clinical observation may be the best therapeutic approach for these
      patients, since most of them have favorable outcomes, whatever the treatment
      modalities.

PMID- 15850002
TI  - Altered fractionation radiotherapy in head and neck cancer: clinical issues and
      pitfalls of "evidence-based medicine".
AB  - The authors present a critical appraisal of the biological bases of altered
      fractionation and a brief overview of published randomized trials with
      conventional fractionation as the control arm, reviews and meta-analysis on
      altered fractionation radiotherapy in head and neck cancer. The major
      controversial issues emerging from these studies are reviewed and the limiting
      factors which so far have prevented the widespread use of altered fractionation
      regimens in current clinical practice are analyzed. Future perspectives regarding
      predictive biological assays for patient selection and the integration of altered
      fractionation regimens with radiochemotherapy protocols, biomodulators and novel
      radiotherapy techniques are also reviewed and summarized.

PMID- 15850003
TI  - Hemoglobin levels and acute radiotherapy-induced toxicity.
AB  - AIMS AND BACKGROUND: To analyze the possible correlation between hemoglobin
      concentration and the appearance of acute radiotherapy-induced toxicity. METHODS:
      We prospectively studied hemoglobin levels and acute radiotherapy-induced
      toxicity in 86 patients treated for 3 months. Both sexes were considered to have
      anemia if their hemoglobin level was < or = 12 g/dL. No patient received
      corrective treatment for hemoglobin levels. Acute toxicity was analyzed weekly
      during radiotherapy and 45 days after therapy ended. The possible relationship
      between anemia and toxicity was analyzed, as was the correlation between
      hemoglobin values and the degree of toxicity. RESULTS: The findings were similar
      for all prognostic factors in patients with and without anemia. Hemoglobin
      concentration was < or = 12 g/dL in 24 patients (27.9%; mean, 10.93 +/- 0.78
      g/dL). At the end of radiotherapy, hemoglobin levels were < or = 12 g/dL in 18
      patients (20.9%; mean, 11.26 +/- 1.06 g/dL). The correlation between pretherapy
      and posttherapy hemoglobin concentration was significant at r = 0.729 (P = 0.01).
      The correlation between absolute hemoglobin values and the degree of toxicity,
      and the possible relationship between hemoglobin concentration and the appearance
      or the degree of toxicity after radiotherapy, was not significant. CONCLUSIONS:
      The relationship between hemoglobin concentration and oxygenation of the tumor
      and healthy tissues was not linear. This may account for the influence of
      hemoglobin levels on control of the disease as reported in earlier studies, but
      it does not account for their influence on acute toxicity after radiotherapy.

PMID- 15850004
TI  - The prognostic value of p53 and c-erbB-2 expression, proliferative activity and
      angiogenesis in node-negative breast carcinoma.
AB  - AIMS AND BACKGROUND: p53, c-erbB-2 and Ki-67 protein expression and microvessel
      density (MVD) determined by CD34 antibody were evaluated by immunohistochemistry
      and their correlation with clinicopathological parameters including estrogen (ER)
      and progesterone (PR) receptor status and survival were investigated in patients
      with axillary lymph node-negative infiltrating ductal breast carcinoma. METHODS:
      The study population consisted of 47 patients with axillary lymph node-negative
      infiltrating ductal breast carcinoma. RESULTS: p53 and c-erbB-2 expression was
      detected in 36.2% and 31.9% of patients, respectively. Median Ki-67 expression
      was 10%. There were no statistically significant differences in the distribution
      of p53, Ki-67 and c-erbB-2 protein expression in relation to the age of the
      patients or to the size, histological grade or ER and PR status of the tumors.
      p53 protein expression correlated positively with c-erbB-2 and Ki-67 protein
      expression (P < 0.05). The mean MVD was 63.65 +/- 29.1 and it correlated
      positively with histological grade and Ki-67 expression (P < 0.05). Survival
      analysis revealed that age, tumor size, p53 and c-erbB-2 expression and PR status
      had no significant prognostic impact, whereas histological grade, proliferative
      activity and angiogenic activity were significant prognostic factors. Although ER
      positive patients had a statistically significant overall survival advantage, the
      difference in disease-free survival was not significant. CONCLUSION: In axillary
      lymph node-negative breast carcinoma the histological grade and the proliferative
      and angiogenic activity of the tumor could be useful prognostic indicators.

PMID- 15850005
TI  - High plasma levels of human chromogranin A and adrenomedullin in patients with
      pheochromocytoma.
AB  - AIMS AND BACKGROUND: The aim of our study was to investigate the plasma
      chromogranin A (CgA) and adrenomedullin (AM) levels in patients with
      pheochromocytomas. METHODS AND STUDY DESIGN: We collected blood samples for
      measurement of plasma CgA and AM in 21 patients with pheochromocytomas, 43
      healthy subjects and 26 patients with solid non-functioning adrenocortical
      adenomas. In 11 patients with pheochromocytomas plasma CgA and AM were measured
      again four weeks after tumor removal. CgA and AM were measured by means of a
      novel solid-phase two-site immunoradiometric assay based on monoclonal antibodies
      (CgA-RIA CT, CIS bio international) and by a specific radioimmunoassay (RIA,
      Phoenix Pharm. Inc.), respectively. RESULTS: The mean plasma CgA level (+/- SD)
      in patients with pheochromocytomas (204 +/- 147.9 ng/mL) was significantly higher
      (P < 0.001) than that in healthy subjects (41.6 +/- 10.7 ng/mL) and in patients
      with non-functioning adrenocortical adenomas (47.3 +/- 17.6 ng/mL). The mean
      plasma AM concentration (+/- SD) in patients with pheochromocytomas (27.5 +/-
      10.4 pg/mL) was significantly higher (P < 0.001) than that in HS (13.8 +/- 4.5
      pg/mL) and in patients with non-functioning adrenocortical adenomas (16.6 +/- 7.3
      pg/mL). Plasma CgA levels correlated with plasma AM levels (r = 0.501; P < 0.02)
      and with plasma metanephrine levels (r = 0.738; P < 0.0001) in patients with
      pheochromocytomas. In 11 patients with pheochromocytomas plasma CgA and AM
      concentrations significantly decreased after tumor removal (P < 0.001 for both).
      Circulating CgA and AM had a sensitivity of 76.2% and 81%, a specificity of 97.7%
      and 90.7%, and an accuracy of 91% and 88%, respectively. CONCLUSION: This study
      demonstrates that circulating CgA and AM levels are increased in pheochromocytoma
      patients compared with healthy subjects and patients with non-functioning
      adrenocortical adenomas. Moreover, at the time of diagnosis plasma CgA levels
      correlated with plasma AM levels and with plasma metanephrine levels in all
      patients with pheochromocytomas. In conclusion, plasma CgA and AM concentrations
      may represent additional biochemical parameters for clinical monitoring of
      patients with pheochromocytomas.

PMID- 15850006
TI  - The role of quantitative polymerase chain reaction in the management of
      follicular lymphoma patients.
AB  - AIMS AND BACKGROUND: In order to increase the prognostic significance of
      polymerase chain reaction (PCR) data it has been suggested that quantitative PCR
      can be used to measure tumor burden. However, this option has not yet been
      definitely supported or refuted in patients with follicular lymphoma (FL). We
      decided to evaluate whether knowledge of the quantitative level of minimal
      residual disease and its variations can be of use in the management of FL
      patients. METHODS: We used qualitative and competitive PCR to study 11 patients
      with refractory or relapsed FL harboring the t(14;18) translocation who underwent
      autologous (nine patients) or allogeneic (two patients) stem cell transplantation
      (SCT). Competitive PCR was performed with a multiple competitor carrying specific
      sequences including Bcl2/IgH MBR and mcr, and the beta-globin gene. RESULTS:
      After a median post-SCT follow-up of 44 months (range, 12-62), overall survival
      was 91% and disease-free survival 82%. The quantitative PCR data showed that: 1)
      effective chemotherapy before SCT substantially (1-2 log) reduced the tumor
      burden in the bone marrow (BM); 2) the increase in rearranged DNA detected in BM
      was associated with disease progression and relapse; 3) a PCR-negative autograft
      seemed to lead to lasting molecular remission even when it was performed in
      patients with a low level of BM infiltration before transplant; and 4) allo-SCT
      made and maintained the BM PCR negative even in the presence of a greater tumor
      burden before SCT. Six of the nine patients having CR after SCT (four auto and
      two allo) are in continuous molecular remission. CONCLUSIONS: In FL patients
      qualitative and quantitative PCR may provide data that can be helpful for the
      prognostic evaluation of tumor progression and the early detection of impending
      relapse by highlighting biological features such as the quality of the infused
      material, the tumor burden at transplant, and the behavior of tumor cells after
      transplant.

PMID- 15850007
TI  - Efficacy of imatinib mesylate in a patient with idiopathic hypereosinophilic
      syndrome and severe heart involvement.
AB  - Idiopathic hypereosinophilic syndrome (HES) is a rare, chronic hematological
      disease mainly characterized by unexplained prolonged eosinophilia, with frequent
      evidence of secondary organ damage. Treatment with steroids, chemotherapy,
      interferon-alpha (IFN-alpha), or imatinib-mesylate may improve the prognosis.
      Here we describe the case of a young male patient with a six-year history of HES
      and severe heart involvement who, after unsuccessful treatment attempts with
      steroids, hydroxyurea and IFN-alpha, had a prompt, clinical and hematological
      complete remission following administration of imatinib. As his cardiac function
      also markedly improved, he was considered for heart transplant. However, seven
      years after the onset of the disease and four months after the termination of
      imatinib treatment the patient died of a cerebral hemorrhage that occurred during
      an episode of acute respiratory sepsis. Imatinib has been previously reported to
      be effective in some hematological conditions with no evidence of the BCR/ABL
      transcript. The mechanisms that are probably involved in the response to imatinib
      in HES are also discussed.

PMID- 15850008
TI  - Complete remission of poorly differentiated squamous liver carcinoma after
      systemic chemotherapy and surgery. A case report.
AB  - We report the case of a 64-year-old male patient diagnosed as having inoperable
      poorly differentiated liver carcinoma that could be completely resected after
      systemic chemotherapy with cisplatin and 5-fluorouracil.

PMID- 15850009
TI  - Primary malignant melanoma of the small bowel: a case report and review of the
      literature.
AB  - Although small bowel involvement by malignant melanoma is most frequently
      metastatic, a primary origin at this site has been reported in rare cases. The
      biological and clinical features of these cases have not yet been summarized.
      Here, another case of small bowel melanoma is described, and a review of the
      existing literature is given. An 81-year-old man presented with anemia and
      gastrointestinal bleeding. A tumor of the ileum was detected by video capsule
      endoscopy and removed by segment resection. Histological examination revealed a
      malignant melanoma of the ileum. Another primary site could be excluded by
      clinical and radiographic examination. The patient felt well five months after
      surgery. Only 18 cases of primary small bowel melanoma (including the present
      one) have been reported to date. A literature review reveals that this rare
      neoplasm is associated with a slight predilection for the male gender, a
      predilection for the ileum and a poor prognosis.

PMID- 15850010
TI  - False negative bone scintigraphy in a patient with primary breast cancer: a
      possible transient phenomenon of bisphosphonate (alendronate) treatment.
AB  - Breast cancer is the most common cancer and the second leading cause of cancer
      deaths among women in developed countries. Bone is a frequent site of metastatic
      disease with a stage-dependent incidence. Most women with breast cancer are at
      risk of osteoporosis due to their age or their breast cancer treatment.
      Scintigraphy enables imaging of the entire skeleton with high sensitivity but
      limited specificity. The false positive rate varies from 1.6% to as high as 22%,
      while the false negative rate varies from 0.96% to 13%. We observed a 70-year-old
      woman with a diagnosis of breast cancer and a false negative bone scan despite
      extensive bone metastases. She was under alendronate treatment for osteoporosis
      at the time. The false negative finding might be due to a transient phenomenon of
      alendronate, a bisphosphonate cleared from the plasma by uptake into bone and by
      renal excretion. 99mTc-MDP is eliminated via the same pathways, and therefore
      competition may occur between the two substances. Another possible explanation
      for the false negative bone scan could be that bone metastases, indicating
      hematogenous tumor spread, are detected earlier by CT scan or MRI than by bone
      scan. Breast cancer patients under bisphosphonate treatment for osteoporosis must
      be carefully evaluated for bone metastasis during radionuclide studies with 99mTc
      MDP.

PMID- 15850011
TI  - Development of squamous cell carcinoma of the tongue during induction
      chemotherapy for acute myeloid leukemia.
AB  - Immunosuppression is a well-recognized cause of skin tumors, in particular
      squamous cell carcinomas (SCC). In patients with hematological malignancies
      undergoing chemotherapy, SCC has been reported late in the course of the disease
      or many years after completion of treatment. Here we report a patient with acute
      myeloid leukemia who developed a SCC of the tongue while receiving the third
      course of induction chemotherapy. This is the second such case in the medical
      literature. The role of immunosuppression, chemotherapy, the malignancy itself
      and possible genetic predisposition is discussed and the literature on this topic
      is reviewed.

PMID- 15850012
TI  - Cervical sympathetic chain schwannoma mimicking a carotid body tumor: a case
      report.
AB  - Carotid body tumor (CBT), the most common tumor of the carotid bifurcation,
      presents as a pulsatile mass. Cervical sympathetic chain (CSC) schwannomas are
      slow growing lesions originating from myelin-producing Schwann cells. They may
      appear pulsatile due to the displacement of vascular structures by the non
      vascular mass and thus may mimic a CBT. A case of CSC schwannoma masquerading as
      CBT in a 25-year-old woman is presented and discussed here.

PMID- 15850013
TI  - Basaloid squamous cell carcinoma of the esophagus: a case report.
AB  - Basaloid squamous cell carcinoma (BSCC) of the esophagus is an extremely rare
      tumor which should be differentiated from adenoid cystic and small cell
      undifferentiated carcinoma. We present the case of a 48-year-old male patient
      with esophageal BSCC. This tumor has specific histological features which may be
      difficult to recognize by small endoscopic biopsy examination. In our patient the
      surgical specimen revealed BSCC with an aggressive pattern (invasion of the whole
      esophageal wall thickness, lymph node metastases and intraneural spread). We
      proposed chemotherapy and radiotherapy after surgery, which resulted in a
      survival of 17 months.

PMID- 15850014
TI  - Case report of synchronous multicentric osteosarcoma and review of the
      literature: the importance of autopsy for diagnosis.
AB  - Synchronous multicentric osteosarcoma is a rare entity with fewer than 100 well
      documented cases in the medical literature. The disease usually progresses
      rapidly in young patients and slightly slower in adults. We present a case of
      synchronous multicentric osteosarcoma with some peculiarities in a 73-year-old
      woman. The diagnosis was made after postmortem examination, which underlines the
      importance of this procedure. This case report is accompanied by a review of the
      literature.

PMID- 15850015
TI  - Solitary squamous cell carcinoma in the kidney after metachronous development of
      esophageal and lung cancer.
AB  - Solitary metastatic renal tumors are rarely encountered clinically. We report the
      case of a 65-year-old man who developed a solitary renal metastasis after
      undergoing an esophagectomy for esophageal cancer and subsequent lobectomy for
      lung cancer. The present case serves to demonstrate that careful follow-up is
      needed for esophageal cancer patients with cancer of another organ.

PMID- 15850016
TI  - Primary orbital liposarcoma in Li-Fraumeni cancer family syndrome: a case report.
AB  - AIMS AND BACKGROUND: The aim of this study was to describe a case of primary
      orbital liposarcoma in Li-Fraumeni syndrome. METHODS AND STUDY DESIGN: In July
      1998 a 20-year-old woman with a histological diagnosis of orbital myxoid
      liposarcoma underwent surgical treatment in our department. Since the patient's
      family pedigree met the clinical criteria for the diagnosis of LFS, molecular
      analysis was performed, which resulted in a molecular profile consistent with Li
      Fraumeni syndrome. RESULTS: The patient underwent orbital exenteration extended
      to the upper eyelid; surgical reconstructive steps were performed to permit
      placement of an orbital prosthesis. Two years after primary surgery the patient
      underwent a quadrantectomy with lymphadenectomy of the right axilla because of
      the presence of a nodule of 1.5 cm in diameter in the upper-lateral quadrant of
      the right breast. One year after the last surgery, the patient is disease free.
      CONCLUSION: The diagnosis of an orbital malignancy in a young patient with a
      family history of cancer should suggest the presence of an underlying genetic
      disorder like LFS; with molecular analysis we can now determine the genetic
      disorder and the exact location of the mutation, and also obtain important
      prognostic data using specific cellular markers. More prognostic information
      increases the chances of adequate personalized treatment.

PMID- 15850017
TI  - Pericardial metastases in a long-surviving patient with sigmoid carcinoma.
AB  - Cardiac metastases are rare in patients affected by colorectal cancer. This is
      the case of a woman who underwent a colon resection because of a metastatic
      sigmoid carcinoma, that survived for more than 6 years and died for malignant
      pericardial effusion.

PMID- 15850018
TI  - Lack of response to imatinib mesylate as second-line therapy in a patient with c
      kit positive metastatic soft tissue leiomyosarcoma.

PMID- 15850019
TI  - Chemotherapy at the end of life: an open question.

PMID- 15850020
TI  - [Role of erythropoietin in the oncology patient: critical review of the
      literature].

PMID- 15850021
TI  - [ESMO 2004. Comparative studies delineating future options in the treatment of
      solid tumors].

PMID- 15850022
TI  - [ESMO 2004. Nausea and vomiting caused by chemotherapy: improving the treatment].

PMID- 15850023
TI  - Why have pesticides become the archetype of all that is wrong with modern
      society?

PMID- 15850024
TI  - Pesticides and human health: why public health officials should support a ban on
      non-essential residential use.
AB  - The College of Family Physicians of Ontario recently released a comprehensive
      report on pesticide exposure and health risk, concluding that various pesticides
      had adverse health effects. The pesticide industry says that pesticides are
      "safe" when used as directed because they are studied and approved by
      governmental agencies. Yet many municipalities, including Canada's three largest,
      and the province of Quebec have enacted bans on cosmetic use of pesticides,
      largely in response to health concerns. Reviewing the report, the status of
      regulation of pesticides and the limitations of studies and of regulation in
      Canada, it appears that on the basis of evidence available to date, public health
      officials should support a ban on cosmetic use of pesticides.

PMID- 15850025
TI  - A reality-based prescription for bloodborne diseases within the corrections
      system.

PMID- 15850026
TI  - Drug use and risk of bloodborne infections: a survey of female prisoners in
      British Columbia.
AB  - BACKGROUND: Clinicians working in a women's prison in British Columbia observed
      hepatitis C sero-conversion among inmates, prompting this study to determine: the
      characteristics of women who do and do not report illicit drug use in prison;
      patterns of drug use inside prison; factors associated with illicit drug use that
      might contribute to bloodborne transmission inside prison. METHODS: A cross
      sectional observational data set was created using an anonymous 61-item self
      administered survey. RESULTS: Eighty-three percent (104/126) of eligible inmates
      participated. Seventy-four percent (77/104) reported their current prison
      sentence was related to illicit drug use and 25% (26/104) reported their
      ethnicity as Aboriginal. Ninety-three percent (97/104) reported a prior history
      of illicit drug use, of whom 70% (68/97) reported a history of injection drug
      use. Thirty-six percent (37/104) reported illicit drug use in prison, and 21%
      (22/104) reported injection drug use in prison. Fifty-two percent (54/104)
      reported hepatitis C sero-positivity, and 8% (8/104) reported HIV sero
      positivity. Of the 22 women who reported prison injection drug use, 91% (20/22)
      reported hepatitis C infection and 86% (19/22) reported injecting with shared
      needles inside prison, with or without bleach cleaning. Women were more likely to
      report illicit drug use in prison if they had had illegal sources of income prior
      to incarceration (p=0.0081, OR 3.19), had previously injected drugs (p=0.036, OR
      2.97), and had first injected drugs at a friend's house (p=0.066, OR 2.70).
      INTERPRETATION: The majority of women reporting prison injection drug use also
      reported hepatitis C sero-positivity and shared needle use. Canadian prisons are
      risk situations for transmission of bloodborne pathogens, and provide
      opportunities for harm reduction strategies.

PMID- 15850027
TI  - Substance use disorders, anorexia, bulimia, and concurrent disorders.
AB  - BACKGROUND: While the co-prevalence of eating disorders (ED) has been documented
      in individuals with substance use disorders (SUD), little is known about the co
      occurrence of other disorders in this population. Examining this issue is
      critical for public health policy and treatment success. OBJECTIVE: To identify
      and evaluate the co-occurrence of ED and other psychiatric disorders in men and
      women with SUD. METHODS: The sample consisted of individuals seeking treatment
      for substance use. Semi-structured interviews and the CAMH Concurrent Disorders
      Screener were completed to assess DSM-IV psychopathology. RESULTS: Chi-square
      analyses suggested that more women scored positive for ED than men, EDs were more
      prevalent in both genders than in the general population, and the co-occurrence
      of other disorders was higher for clients with both SUD and ED than with SUD.
      DISCUSSION: Individuals with both SUD and ED appear to have multiple needs that
      may not be readily assessed by existing addiction treatment programs. Assessment
      issues, treatment, potential prevention and health promotion implications are
      addressed.

PMID- 15850028
TI  - HIV and hepatitis C outbreaks among high-risk youth in Vancouver demands a public
      health response.
AB  - This paper is a call to action. We present Kaplan Meier cumulative HIV and HCV
      incidence rates among youth aged < or = 24 participating in the Vancouver
      Injection Drug Users Study (VIDUS), and demonstrate the alarming increase in HIV
      and HCV incidence rates in addicted youth. The incidence rates among VIDUS youth
      were 11.1% for HIV and 52.1% for HCV at 36 months after enrollment in the study.
      The growing epidemic of HIV and HCV among addicted youth calls for policy-makers
      and program planners to concentrate resources into prevention and treatment of
      blood-borne infections among British Columbia's vulnerable youth. Without
      focussing such resources, further HIV and HCV infections and subsequent higher
      health care costs appear imminent.

PMID- 15850029
TI  - West Nile Virus: the buzz on Ottawa residents' awareness, attitudes and
      practices.
AB  - BACKGROUND: In 2002, the City of Ottawa was interested in the public perception
      of West Nile Virus (WNV) and mosquito control. Their objectives were to assess:
      awareness of WNV, practices to reduce mosquito sources, personal protective
      measures, and attitudes towards community-based insecticide programs. METHODS: In
      July 2002, we administered a telephone survey to a random, stratified sample of
      urban, suburban and rural Ottawa households. RESULTS: Surveys were completed for
      491 households. Most (77.2%) respondents reported they had heard of WNV, and of
      these, 58.3% reported WNV was an important health issue. Mosquito repellent was
      the most common personal protective measure, reported among 72.5% of respondents,
      of whom 76.9% used DEET products. Multivariate regression analyses showed that
      age was a significant predictor of repellent use, with respondents aged less than
      51 years more likely to use repellent than older respondents (ORadj =2.0; 95% CI:
      1.2-2.3). This age group was also more likely to use at least one personal
      protective behaviour (ORadj = 2.5; 95% CI: 1.4-4.5). Of 315 people selecting a
      justified time to larvicide, 4.8% chose "larvicides should never be used in
      Ottawa"; 33.4% stated that larviciding would be appropriate "when WNV was
      detected in birds or mosquitoes"; one third "needed more information" on the
      health and environmental effects of insecticides, prior to selecting a response.
      CONCLUSIONS: Our findings highlight the need for public education reinforcing WNV
      importance, emphasizing the health and environmental effects of insecticides as
      well as appropriate personal protective behaviours. Such messages should target
      older and urban residents.

PMID- 15850030
TI  - Conquering the crippler: Canada and the eradication of polio.

PMID- 15850031
TI  - [Is it possible to sustain health promotion programs in private companies? The
      case of four Quebec private companies of blue collar workers].
AB  - OBJECTIVE: Sustained health promotion programmes in the workplace (HPPW)
      continues to be a public health challenge. This article presents an evaluation of
      the implementation and sustainability of such programmes in private blue-collar
      companies in Quebec to shed light on issues specific to this type of setting.
      METHOD: A multiple case (4 sites), longitudinal (7 years) and interpretive study
      method was used. The interpretation framework considered that the implementation
      and sustainability of HPPW in companies are the result of organizational learning
      in health promotion, determined by the strategies of individuals in a position of
      control who shape the decisional processes related to these programmes. RESULTS:
      After seven years of observation, two of the four sites had continued their HPPW,
      although these programmes were no longer applied within these companies. The
      health promotion organizational learning processes in both sites were defined
      according to targeted organizational purposes set by the decision-makers who
      supported HPPW. However, these gains were largely lost when HPPW were no longer
      retained as a component of their organizational development strategy. DISCUSSION:
      The organizational conditions that are conducive to HPPW are difficult to put
      together and sustain in companies like those in our study. Businesses implement
      these programmes mainly for the organizational benefits they expect to reap in
      the short term, whereas improvement in the health of workers in the longer term
      is not a priority.

PMID- 15850032
TI  - [Media treatment of messages on weight loss products by the Association for
      Public Health of Quebec and its reception].
AB  - BACKGROUND: The results of a study on weight loss products and services were
      released during a press conference organized by the Association pour la sante
      publique du Quebec (ASPQ). The media widely covered this press conference. The
      purpose of this article is to answer the question: "How are messages emitted by
      public health institutions transmitted by the media and received by the
      population?" METHOD: The transcripts of the press conference, the press release
      as well as 43 documents from the print and broadcast media were evaluated
      according to a press analysis method. The analysis of these documents was based
      on the concept of the information unit. The compilation of these information
      units was used to produce charts which include data such as the frequency,
      partiality, weight tendency ("poids-tendance") and tendency-impact ("tendance
      impact"). Furthermore, two focus groups of persons using weight loss products and
      services were conducted. RESULTS: In this article, we compare the emitted message
      with the one transmitted. The analysis of the message emitted by the ASPQ and
      that conveyed by the media revealed that for almost all subjects dealt with
      during the press conference, the media have been more partial than the ASPQ. The
      media not only expanded on the emitted message but also gave a negative image of
      weight loss products and services. Furthermore, the message transmitted by the
      media was very similar to the initial message. The focus groups on how the
      message was received by persons using weight loss products and services also
      revealed that the message was lost in the flow of information on weight loss
      products and services. CONCLUSION: This analysis of the emitted, transmitted and
      received messages has given us some indications on how to readjust the initial
      message and on what to emphasize in future press conferences.

PMID- 15850033
TI  - Long-term health sequelae following E. coli and campylobacter contamination of
      municipal water. Population sampling and assessing non-participation biases.
AB  - BACKGROUND: Following bacterial contamination of a municipal water system in the
      rural town of Walkerton, Ontario, over 2,300 cases of acute gastroenteritis were
      documented. The Walkerton Health Study is currently underway to assess for long
      term health sequelae among consenting inhabitants of Walkerton, related to the
      original outbreak. We explored whether the association between the acute exposure
      and preliminary long-term health outcomes may have been biased through
      differences between early- and late-recruited study participants. METHODS: Using
      multiple data sources, including the 1996 and 2001 Canadian Census, and records
      from the Regional Health Unit, hospital and Walkerton Health Study, we determined
      both sample representativeness and the anticipated effects of intensifying study
      participant recruitment. Selection bias was assessed by examining for differences
      between initial and late participants, and their subsequent risk of having
      hypertension, proteinuria and reduced renal clearance. RESULTS: Of the 4,315
      participants, 2,756 were permanent residents of Walkerton, representing 55% of
      the town's total population. The sample was demographically similar to the
      population of interest, although statistically women were more likely to
      participate than men (55% of sample were women compared to 52% of population,
      p<0.01), and the proportion of both young and very elderly adults was smaller
      than expected (13% of sample were > or = 65 years of age compared to 18% of
      population, p<0.01). Comparing the initial 3,959 participants to the 356 persons
      additionally recruited with substantial effort, the latter were more likely to be
      free of symptoms during the outbreak (21% vs. 7%, p<0.001), but were otherwise
      similar in terms of age, sex, the use of medical care resources and underlying
      health state predating the outbreak. The risk of long-term hypertension or renal
      sequelae did not significantly differ between initial and late study recruits.
      CONCLUSIONS: Participants in the Walkerton Health Study represent the population
      of interest, and comprise those who were acutely ill during the infected water
      outbreak. The available study sample should provide reasonably unbiased estimates
      of the associated risk between acute bacterial gastroenteritis and long-term
      health sequelae.

PMID- 15850034
TI  - Current trends in youth suicide and firearms regulations.
AB  - BACKGROUND: Despite numerous prevention initiatives, suicide remains the second
      leading cause of death in youth aged 10-19. One of the major prevention
      strategies is the introduction of restrictive firearms regulations. For example,
      Bill C-17 was enacted in 1991 to promote safer handling and storage of firearms
      through mandatory safety courses for all new gun owners. Examining the suicide
      rates subsequent to Bill C-17 may shed light on the possible benefit of these
      regulations as a solution to this major public health issue. Therefore, this
      paper examines the trends in youth suicide from 1979-1999 and the association
      with changes in the firearms act in 1991. METHODS: Age-specific suicide rates for
      youth between 15-19 years and rates by methods of suicide were calculated based
      on data from Statistics Canada for the years 1979-1999. Time series analyses were
      conducted. RESULTS: Although the overall rates did not change from 1979-1999 in
      youth aged 15-19, there was a substantial change in the methods used. In
      particular, the rates of suicide by firearms dropped from 60% to 22% while
      suicide due to hanging/suffocation increased from 20% to 60% in this age group
      over this period of time. CONCLUSION: These results suggest a possible
      association between changes in the firearms act in 1991 and the methods used by
      youth to complete suicide. However, the overall rates of suicides did not change
      over this same period. These trends underscore the need for broader prevention
      interventions that do not solely focus on methods of suicide but rather, their
      underlying causes.

PMID- 15850035
TI  - Family physician visits and early recognition of melanoma.
AB  - BACKGROUND: Malignant melanoma is a deadly skin cancer with a rapidly-increasing
      incidence, mortality and public health burden. Thin melanomas are easily treated
      with good prognosis, while the thicker lesions have relatively poor survival. To
      broaden strategies for early recognition of melanoma, we investigated the
      relationship between primary care service and melanoma thickness at diagnosis.
      METHODS: All 714 patients diagnosed with a primary malignant melanoma between
      January 1995 and December 1999 in Nova Scotia were included in the present study
      and linked to provincial physician billing databases to reveal the patients' use
      of family physician services prior to the diagnosis of melanoma. We examined the
      importance of physician use of services for tumour thickness using logistic
      regression while adjusting for potential confounders. Tumour thickness was
      dichotomized to thin and thick using 0.75 mm as a cutoff. RESULTS: Patients who
      regularly visited their family physician (2 to 5 times during a two-year interval
      prior to diagnosis) were 66% (95% CI, 31-84) less likely to be diagnosed with
      thick melanoma as compared to patients who consulted their family physician less
      or not at all. Progression to thick tumours could have been reduced by 11.70%
      (95% CI, -1.33-25.77) if all patients had consulted their family physician at
      least once a year. DISCUSSION: Increased awareness of the need for regular
      medical check-ups could reduce the public health burden of melanoma.

PMID- 15850036
TI  - Comparison of papanicolaou (Pap) test rates across Ontario and factors associated
      with cervical screening.
AB  - BACKGROUND: Cervical cancer remains a significant yet preventable disease despite
      the widespread availability of Pap test screening, which detects cervical cancer
      and its precursor lesions. The aims of this study were to: i) estimate and
      compare age- and hysterectomy-adjusted Pap test rates across the 37 Ontario
      public health units (PHUs), and ii) explore the association between several
      factors and Pap test rates (at the ecological level). METHODS: Cytobase, an
      Ontario Pap test registry, captures more than 80% of all Pap tests in Ontario.
      Cytobase was used to determine Pap test rates adjusted for age, hysterectomy and
      Cytobase coverage for the year 2001. Multiple linear regression analyses were
      used to evaluate the relationship between Pap test rates and various factors at
      an ecological level, RESULTS: Age-, hysterectomy- and Cytobase-adjusted one-year
      Pap rates ranged from 11.6% to 73.9% among PHUs. The overall rate for Ontario was
      40.7%. Multivariate analyses indicated that the presence of a teaching hospital
      was associated with higher Pap test rates. CONCLUSION: One-year Pap test rates
      varied greatly across the 37 public health units in Ontario. Pap test rates
      determined using Cytobase were lower than self-reported rates obtained from the
      Canadian Community Health Survey, possibly due to "over-reporting". In general,
      women were not screened as frequently as recommended by the Ontario Cervical
      Screening Program. A positive association was observed between Pap test rates and
      the presence of a teaching hospital. Data quality issues limit the ability to
      monitor cervical screening. A provincial registry would address these issues.

PMID- 15850037
TI  - An evaluation of the Ontario Rapid Risk Factor Surveillance System.
AB  - BACKGROUND: The Rapid Risk Factor Surveillance System (RRFSS) is an ongoing
      population health survey conducted by a collaborating group of Ontario public
      health units. This formative evaluation examined the process effectiveness,
      collaboration, utility and cost-effectiveness of RRFSS during its first year of
      operation. METHODS: An Evaluation Framework was developed with reference to
      guidelines for evaluation of surveillance systems developed by the World Health
      Organization and the U.S. Centers for Disease Control and Prevention. The study
      focussed on evaluable performance areas in a young surveillance system and on
      information needed to inform stakeholder decisions about future participation and
      improvement. Data were collected through surveys and interviews of key informants
      in participating health units, non-participating health units, the survey
      research house, and the provincial health ministry. RESULTS: Findings documented
      early use and dissemination of RRFSS data in health units after less than a year
      of surveillance system operation, stakeholder perceptions overall of data impact
      and value, and satisfaction with system functioning. Challenges to effectiveness
      were documented concerning data analysis, barriers to data use, and
      sustainability. Performance improvement strategies were identified for survey
      implementation and supports, data use, system participation, and reduced costs.
      CONCLUSION: In its first year, RRFSS was an effective collaborative method to
      collect population data for public health program planning and evaluation. The
      evaluation provided valuable information on use, functioning, effectiveness,
      strategic issues and areas for improvement in a young surveillance system,
      created opportunities for stakeholder input into evaluation and planning, and
      provided a baseline for future evaluations.

PMID- 15850038
TI  - Linking survey data with administrative health information: characteristics
      associated with consent from a neonatal intensive care unit follow-up study.
AB  - BACKGROUND: Health services and population health research often depends on the
      ready availability of administrative health data. However, the linkage of survey
      based data to administrative data for health research purposes has raised
      concerns about privacy. Our aim was to compare consent rates to data linkage in
      two samples of caregivers and describe characteristics associated with
      consenters. METHODS: Subjects included caregivers of children admitted at birth
      to neonatal intensive care units (NICU) in British Columbia and caregivers of a
      sample of healthy children. Caregivers were asked to sign a consent form enabling
      researchers to link the survey information with theirs and their child's
      provincially collected health records. Bivariate analysis identified sample
      characteristics associated with consent. These were entered into logistic
      regression models. RESULTS: The sample included 1,140 of 2,221 NICU children and
      393 of 718 healthy children. The overall response rate was 55% and the response
      rate for located families was 67.1%. Consent to data linkage with the child data
      was given by 71.6% of respondents and with caregiver data by 67% of respondents.
      Families of healthy children were as likely to provide consent as families of
      NICU children. Higher rates of consent were associated with being a biological
      parent, not requiring survey reminders, involvement in a parent support group,
      not working full-time, having less healthy children, multiple births and higher
      income. CONCLUSION: The level of consent achieved suggests that when given a
      choice, most people are willing to permit researcher access to their personal
      health information for research purposes. There is scope for educating the public
      about the nature and importance of research that combines survey and
      administrative data to address important health questions.

PMID- 15850039
TI  - Improving the public health/physician partnership for influenza vaccination.
AB  - BACKGROUND: Alberta doctors can request supplies of publicly funded influenza
      vaccine to administer to patients who meet provincial program criteria. PURPOSE:
      To describe the proportions of Alberta family doctors who vaccinate patients, the
      sources from which they obtain vaccine and their evaluation of public health
      influenza vaccination program components. METHODS: Cross-sectional postal survey,
      2003. Doctors were asked to complete a nine-page questionnaire or to answer a one
      page "mini-survey". The proportion of physicians who vaccinated patients against
      influenza was estimated separately for the main questionnaire and the mini
      survey. Frequencies and cross-tabulations were used to examine sources of vaccine
      supply and physician ratings of five aspects of influenza vaccine program
      services provided by Regional Health Authorities (RHA). RESULTS: The survey
      response rate was 52.3% (1387/2650); an additional 14% (372) returned a mini
      survey. The proportion of respondents who vaccinated one or more patients against
      influenza in the fall of 2002 was 81.5% for the main questionnaire and 83.1% for
      the mini-survey. Vaccine was most commonly obtained from the RHA. Three items
      were rated as poor/fair by more than 10% of respondents: provision of information
      for distribution to patients (37%), timeliness of vaccine delivery to offices
      (16%) and vaccine availability over the entire influenza season (18%). Item
      ratings varied by RHA but provision of information for distribution to patients
      was consistently a problem. CONCLUSION: A high priority should be placed on
      improving resources for doctors to give to patients, timeliness of vaccine
      deliveries to doctors' offices and vaccine availability over the entire season.

PMID- 15850040
TI  - A window into Richard M. Zaner's clinical ethics.
AB  - This essay introduces a thematic issue focused on the contributions to clinical
      ethics and the philosophy of medicine by Richard M. Zaner. We consider the
      apparent divorce of Zaner's philosophical roots from his recent narrative
      immersions into the blooming, buzzing confusions of clinical-moral lifeworlds.
      Our considerations of the Zanerian context and origins of the clinical encounter
      introduce the fundamental questions faced by Zaner and his commentators in this
      issue, questions about the role of ethics consultants, moral authority, and
      clinical truths.

PMID- 15850041
TI  - What kind of doing is clinical ethics?
AB  - This paper discusses the importance of Richard M. Zaner's work on clinical ethics
      for answering the question: what kind of doing is ethics consultation? The paper
      argues first, that four common approaches to clinical ethics -- applied ethics,
      casuistry, principlism, and conflict resolution cannot adequately address the
      nature of the activity that makes up clinical ethics; second, that understanding
      the practical character of clinical ethics is critically important for the field;
      and third, that the practice of clinical ethics is bound up with the normative
      commitments of medicine as a therapeutic enterprise.

PMID- 15850042
TI  - Richard Zaner's "troubled" voice in Troubled Voices: poseur, posing,
      possibilizing?
AB  - This essay considers Richard Zaner's storytelling in Troubled Voices as a form of
      possibilizing which uses the stories to exemplify important moral themes such as
      contingency and freedom. Distinguishing between activities of moral discovery
      through the telling of a story and "posing" in the sense of writing to tell the
      "moral" of the story, I suggest that something crucial goes on for Zaner in his
      own tellings. Several of the more insistent implications Zaner reveals about the
      moral relationships encountered in the activity of clinical ethics consultation
      are examined in that light, especially regarding this question: is it more
      beneficial, or harmful, to articulate elements of core meanings and values that
      are entailed in individual viewpoints, which, prior to an ethics consultant's
      participation, may have remained unspoken and possibly unacknowledged?

PMID- 15850043
TI  - Ethical reasoning and the embodied, socially situated subject.
AB  - My discussion is concerned with how symbolic power constitutively structures our
      very identities in relation to one another and at the bodily level of lived
      experience. Although many accounts of the self and of subjectivity as socially
      situated have difficulties in their explanations of agency, Zaner's work suggests
      a basis upon which the self's independence from others can be understood. His
      phenomenology of embodied subjectivity explains how the emerging self presupposes
      presence with others. At the same time, however, "co-presence" also reveals the
      self's distinct perspective and capacity for "circumstantial possibilizing," that
      is to say, "actualizing another possible than the actual." My aim is to examine
      critically the intersections between Zaner's phenomenology and other theoretical
      accounts of the socially situated self. I also show how Zaner's work contributes
      to these discussions a way of understanding the possibility of agency that is
      rooted in embodied experience.

PMID- 15850045
TI  - A work in progress.
AB  - After expressing gratitude to each contributor, and briefly commenting on each, I
      probe several main themes of my work, addressing the question of the apparent
      difference between my earlier "philosophical" and later "clinical" writings.
      Central to both is the reflexivity of the human agent, and that each exhibits a
      form of practice regardless of the specific aims embedded in each. I then address
      the theme of narrative writing as my work has developed over the past several
      decades at the heart of which are questions of self and integrity.

PMID- 15850044
TI  - Richard Zaner's phenomenology of the clinical encounter.
AB  - The "clinical ethics" propounded by Richard Zaner is unique. Partly because of
      his phenomenological orientation and partly because of his own daily practice as
      a clinical ethicist in a large university hospital, Zaner focuses on the
      particular concrete situations in which patients and their families confront
      illness and injury and struggle toward workable ways for dealing with them. He
      locates ethical reality in the "clinical encounter." This encounter encompasses
      not only patient and physician but also the patient's family and friends and
      indeed the entire "lifeworld" in which the patient is still striving to live. In
      order to illuminate the central moral constituents of such human predicaments,
      Zaner discusses the often-overlooked features of disruption and crisis, the
      changed self, the patient's dependence and the physician's power, the violation
      of personal boundaries and their necessary reconfiguring, and the art of
      listening.

PMID- 15850046
TI  - The killers next door. Brutal new drug gangs are terrorizing the US-Mexico
      border.

PMID- 15850047
TI  - You must be over 21 to drink in this living room. A crackdown on house parties
      stirs up a debate about privacy.

PMID- 15850048
TI  - The bully blight. Scientists find that getting picked on is more harmful than
      anyone knew.

PMID- 15850049
TI  - Quality care.

PMID- 15850050
TI  - [Efficacy of therapeutic and prophylactic actions of ultralow doses of antibodies
      to gamma-interferon in experimental murine model of herpes virus].
AB  - The process of the disease due to herpes simplex virus types 1 and 2 (HSV-1 and
      2) was studied on white uninbred mice weighing 10 to 12 g. The animals were
      infected intracerebrally or intraperitoneally. Intraperitoneal contamination of
      the animals with MS strain of HSV-2 was used for the experimental model of the
      herpes simplex infection. The prophylactic antiherpes action of ultralow doses of
      the human gamma-interferon antibodies (ULD of anti-IFN-gamma) at a course of its
      intragastral administration was evaluated. The preparation was shown to have a
      significant (p < 0.05) protective effect in a dose of 10 LD50, evident from a 10
      fold decrease of the HSV-2 accumulation in the brain, a lower percentage of the
      animal deaths and an increase of the average lifespan of the animals by 3.3 days.
      The study of the therapeutic action of ULD of anti-IFN-gamma at a course of its
      intragastral administration showed that the preparation had no significant
      positive effect on the disease process in the animals infected with HSV-2 in a
      dose of 10 LD50. However, a positive effect associated with delayed virus
      replication in the brain was observed in the study on the therapeutic effect of
      ULD of anti-IFN-gamma after its intragastral administration to the mice infected
      with a sublethal dose of the virus.

PMID- 15850051
TI  - [Role of some representatives of opportunistic microflora in development of
      secondary infection in patients with pulmonary tuberculosis].
AB  - The results of the laboratory diagnosis of secondary (mixed) infection of the
      respiratory tracts in patients with respiratory tract tuberculosis were
      summarized. The study was performed for 12 months in a Tuberculosis Clinic. The
      species of the pathogens and the frequency of their detection in various clinical
      specimens from pulmonary tuberculosis patients were determined. The data on
      resistance of the strains of Streptococcus viridans group isolated from the
      pulmonary tuberculosis patients to various antimicrobials including new
      fluoroquinolones are presented.

PMID- 15850052
TI  - [Azithromycin levels in the chorion tissue within the first three months of the
      pregnancy term].
AB  - The levels of azithromycin in the chorion tissue within the first 3 months of the
      pregnancy term (42 to 56 days post coitus) were determined. Three days after the
      use of azithromycin (Sumamed) the antibiotic concentration in the villi tissue
      was 0.065 to 0.26 mcg/mg (the average of 0.129 mcg/mg). The azithromycin
      concentration above 0.125 mcg/mg was detected in 38.5% of the women. The results
      confirmed the fact of significant azithromycin accumulation in the chorion
      tissue. The percentage of the azithromycin transplacental transfer within the
      above mentioned pregnancy term varied from 2.3 to 9.3 (the average of 4.6).

PMID- 15850053
TI  - [Antibiotic prophylaxis, antibiotic therapy and microbiological situation in
      surgical unit].
AB  - The clinical and economic efficacies of antibiotic prophylaxis in the surgical
      unit of the Hospital were confirmed by the results of the analysis of 1313 case
      records of the patients operated during a year for acute appendicitis and acute
      cholecystitis. At the same time it was shown advisable to use antibiotic therapy
      in the patients with various pathological processes. The dynamics of the
      microbial dissemination in the surgical unit and some other units of the
      Hospital, as well as the dynamics of antibiotic resistance of the microflora, its
      interrelation with the volume of the antibacterials used and their rotation are
      described.

PMID- 15850054
TI  - [Experience with rotation of basic antibiotics in intensive care unit of
      cardiosurgical hospital].
AB  - Clinical and microbiological efficacies of antibiotic rotation in the intensive
      care unit of the Hospital were evaluated. The results of the local
      microbiological monitoring of the profile of the acquired resistance of
      gramnegative nosocomial pathogens (n = 151) isolated from adult patients with
      artificial ventilation of the lungs for more than 3 days after the open heart
      operations (n = 150) were analysed. Three 6-month cycles of cephalosporins
      rotation in the following order were performed: cefoperazone--ceftazidime-
      cefepime. The procedure provided a significant decrease in the frequency of
      infectious complications (7.2 vs. 4.5%, p=0.015). The rotation did not require
      any increase of the use of reserve antibiotics such as vancomycin and
      carbapenems. The use of the drugs active against Pseudomonas aeruginosa promoted
      its eradication in the structure of the nosocomial pathogens in the intensive
      care unit.

PMID- 15850055
TI  - [Antibiotic-associated diarrhea and enteric candidiasis: possible treatment and
      prophylaxis].

PMID- 15850056
TI  - [Study of cefepime in Russia].

PMID- 15850057
TI  - [Complete anterior cruciate ligament tears in children].

PMID- 15850058
TI  - [Computer-assisted surgery of the anterior cruciate ligament].

PMID- 15850059
TI  - [Arthroscopic anatomy of the shoulder].

PMID- 15850060
TI  - [Arthroscopic treatment of impingement and partial thickness tears of the rotator
      cuff of the shoulder].

PMID- 15850061
TI  - [Meniscal repair].

PMID- 15850062
TI  - Percutaneous ablation therapy for hepatocellular carcinoma: current practice and
      future perspectives.
AB  - Worldwide, hepatocellular carcinoma (HCC) is a common, refractory, malignant
      tumor. Surgical resection is feasible in only a few patients, because of limited
      hepatic reserve and multifocality of tumors at diagnosis. Percutaneous ablation
      therapies, including injection of ethanol (PEI) or acetic acid (PAI),
      radiofrequency ablation (RFA), and microwave coagulation therapy (MCT), have been
      the major treatments for unresectable HCC in the past decade. PEI is well
      established for small (<3 cm) HCC, and PAI is equally as effective as PEI, but
      with fewer treatment sessions. RFA has recently been suggested to have excellent
      tumor-ablating ability because it produces a fixed and predictable tumor necrosis
      zone. Although RFA is also effective for medium-sized HCC, the overall
      complication rate may be higher than previously assumed. MCT is similar to RFA in
      its clinical application and potential adverse effects. A combination approach
      using percutaneous ablation therapy and transcatheter arterial embolization was
      shown to be effective for large HCC. Other approaches, such as injection of hot
      saline or yttrium-90 microspheres, cryoablation, or interstitial laser
      photocoagulation, are less often used nowadays. Multimodal, image-guided,
      tailored therapy, rather than a fixed treatment algorithm, might be more
      practical for unresectable HCC. In conclusion, although longterm survival is
      possible in selected patients with HCC, the overall prognosis remains suboptimal,
      especially in patients with unfavorable tumor characteristics. While newer anti
      tumor therapies with improved efficacy are needed, information about a more
      rational approach to the use of existing therapeutic options may help to enhance
      treatment strategies for HCC.

PMID- 15850063
TI  - Third-line chemotherapy for advanced non-small-cell lung cancer--is there enough
      evidence to support its use?

PMID- 15850064
TI  - Gleason score from needle biopsy of the prostate predicts that from radical
      prostatectomy in most cases.

PMID- 15850065
TI  - Clinical experience with single-agent gemcitabine chemotherapy in patients with
      non-small-cell lung cancer in whom previous chemotherapy has failed.
AB  - BACKGROUND: In a phase II study, responses and toxicity to single-agent
      gemcitabine chemotherapy were evaluated in patients with non-small-cell lung
      cancer (NSCLC) who had failed previous cisplatin-based chemotherapy. METHODS:
      Twenty patients were enrolled from December 2001 to December 2003: 17 of them had
      received first-line cisplatin-based regimens and second-line docetaxel treatment;
      and 3 had previously received cisplatin plus paclitaxel. Study treatment
      comprised an intravenous infusion of gemcitabine 1200 mg/m2 on days 1, 8, and 15
      of each 4-week cycle. RESULTS: Fifty-seven cycles of treatment were given (mean,
      2.9 cycles per patient). All patients were evaluable for toxicity profile, and 16
      were evaluable for response rate. The principal toxicity was myelosuppression:
      grade 3 neutropenia occurred in 2 patients (10%), thrombocytopenia in 3 (15%),
      and anemia in 1 (5%). Other toxicities were few and mild in severity. After 2
      cycles of treatment, 2 of 16 patients (12.5%) had a partial response. The median
      time to disease progression was 2.1 months, and median survival time was 7.5
      months. The 1-year survival rate was 36%. CONCLUSION: Salvage, single-agent
      chemotherapy with gemcitabine has modest activity, is well tolerated, and yields
      good survival in NSCLC patients who have failed previous chemotherapy. Such
      single-agent therapy may therefore be suggested for use in patients with good
      performance status who ask for further chemotherapy, when disease progresses
      after cisplatin-based therapy, but especially after second-line docetaxel
      therapy.

PMID- 15850066
TI  - Correlation of Gleason scores between needle-core biopsy and radical
      prostatectomy specimens in patients with prostate cancer.
AB  - BACKGROUND: The histologic grade of a prostate needle-core biopsy specimen can
      determine whether a patient with prostate cancer is a candidate for radical
      prostatectomy or other treatment. Incorrect histologic grading can result in
      inappropriate treatment and possible liability. Thus, we conducted this study to
      determine the histologic-grading accuracy of prostate cancer needle-core biopsy
      specimens. METHODS: Fifty-two patients with localized prostate cancer treated
      with radical prostatectomy were included in the study. The overall correlation
      between Gleason scores for needle-biopsy and prostatectomy specimens was
      evaluated by analyzing the following parameters: biopsy-core number; accurate
      biopsy-core length; prostate volume; and preoperative, serum prostate-specific
      antigen (PSA) level. A "downgrade" was defined as the Gleason score for the
      prostatectomy specimen being greater than that for the biopsy specimen, whereas
      an "upgrade" was defined as the converse. RESULTS: No difference in Gleason
      scores was noted for 31% of specimens, whereas a downgrade was noted for 40%, and
      an upgrade for 29%. The accuracy of Gleason scores for biopsy specimens taken by
      the sextant systemic-biopsy method increased when specimens were >15 mm in
      length. No correlation was noted between difference in Gleason scores and biopsy
      core number, prostate volume, and preoperative serum PSA level. CONCLUSION: The
      accuracy of Gleason scores determined by needle biopsy in patients with prostate
      cancer seems to be unreliable. Therefore, further evaluation of patients is
      necessary. No correlations were noted between biopsy-measured errors in Gleason
      score and biopsy number, prostate volume, or preoperative serum PSA level.

PMID- 15850067
TI  - Increased intra-abdominal pressure causes bacterial translocation in rabbits.
AB  - BACKGROUND: Abdominal compartment syndrome (ACS) is defined as intra-abdominal
      hypertension associated with organ dysfunction. Subsequently, increased intra
      abdominal pressure (IAP) adversely affects the pulmonary, cardiovascular, renal,
      musculoskeletal/integumentary and central nervous systems. Bacterial
      translocation (BT), which is defined as the movement of viable enteric bacteria
      to the mesenteric lymph nodes, liver and spleen, occurs after various types of
      stress and results in splanchnic ischemia. In this experimental study, we aimed
      to investigate the effects of various levels of increased IAP on BT in rabbits;
      IAP was increased by the intra-abdominal balloon-insufflation method, thus
      simulating noncompliant abdominal-wall closure under tension. METHODS: Fifty
      rabbits were randomly assigned to 1 of 5 groups, with each group comprising 10
      animals. In group I (control group), an intra-abdominal balloon was placed
      without inflation. In groups II, III, IV and V, IAPs of 10, 15, 20 and 25 mmHg,
      respectively, were established via inflation of the intra-abdominal balloon. All
      groups underwent laparotomy after 12 hours. Multiple biopsies were taken from
      ileocecal lymph nodes, the spleen and liver. RESULTS: BT was observed to some
      degree in all 4 experimental groups. A gradual increase in the phenomenon was
      noted as IAP increased from 10 to 15 mmHg; and BT was overt at 20 mmHg, and
      significant at 25 mmHg. Klebsiella pneumoniae, Serratia marcescens, and
      Escherichia coil were the predominant pathogens identified by culture.
      CONCLUSION: We propose that an intravesical pressure (IVP) of 15 mmHg is the
      critical point for BT in patients with increased IAP. In this experimental study,
      BT occurred when IVP reached 20 mmHg. We suggest that IVP monitoring is desirable
      in the management of patients with ACS, and that decompressive laparotomy should
      be performed in patients with IVP >20 mmHg.

PMID- 15850068
TI  - Correlation between voiding and erectile function in patients with symptomatic
      benign prostatic hyperplasia.
AB  - BACKGROUND: The relationship between lower urinary tract symptoms and male sexual
      dysfunction remains controversial. In this study, we aimed to evaluate the
      relationship between voiding and erectile function (EF) using the American
      Urological Association Symptom Index (AUA-SI) and International Index of EF (IIEF
      15) in patients with benign prostatic hyperplasia (BPH). METHODS: From March 2001
      to January 2002, 50 men (aged 43-92 years) with symptomatic BPH were enrolled in
      the study. They completed the AUA-SI and IIEF-15 questionnaires. An additional
      question about subjective erectile dysfunction (ED) was also evaluated. AUA-SI
      scores were divided into 3 categories (irritative, obstructive, and total), and
      IIEF-15 scores were divided into 6 categories (EF, orgasmic function [OF], sexual
      desire [SD], intercourse satisfaction [IS], overall satisfaction [OS], and
      total). RESULTS: Irritative, obstructive and total AUA-SI scores were 7.8 +/-
      3.7, 8.4 +/- 5.6 and 16.3 +/- 8.2, respectively. Scores in the 6 categories of
      the IIEF-15 questionnaire were as follows: EF, 12.1 +/- 10.1; OF, 3.7 +/- 3.8;
      SD, 4.4 +/- 2.0; IS, 4.5 +/- 4.4; OS, 4.4 +/- 2.6; and total, 29.4 +/- 22.2. No
      obvious correlation was noted between AUA-SI and IIEF-15 scores. Further, no
      statistical significance was noted, either between AUA-SI and IIEF-15 severity,
      or between AUA-SI and EF severity. Among 22 patients who self-reported the
      absence of ED, 17 (77%) had an EF-domain score less than 26. The mean age of
      patients with, versus those without, ED was significantly greater. CONCLUSION:
      Voiding and EF, assessed by the AUA-SI and IIEF-15 questionnaires, respectively,
      are not correlated in patients with BPH.

PMID- 15850069
TI  - Interstitial pneumonia during gefitinib treatment of non-small-cell lung cancer.
AB  - Gefitinib, an orally active, selective inhibitor of epidermal growth factor
      receptor tyrosine kinase, is an effective treatment for patients with advanced
      non-small-cell lung cancer (NSCLC). Most drug-related adverse events are mild to
      moderate; however, some patients may develop acute interstitial pneumonia that is
      sometimes fatal. In a prospective study of gefitinib in 76 patients with advanced
      NSCLC, 69 patients were evaluable for toxicity, and 4 cases (5.8%) of gefitinib
      related interstitial pneumonia were diagnosed: 1 occurred in the second week; 2
      in the second month; and 1 during the fourth month of treatment. When
      interstitial pneumonia occurred, the patients had stable disease (n = 2), a
      partial response (n = 1), or progressive disease (n = 1). All 4 patients
      recovered when gefitinib treatment was stopped and glucocorticosteroid therapy
      was started; no deaths related to gefitinib therapy were noted in this series.
      While treating NSCLC patients with gefitinib, it is important to carefully
      evaluate any new-onset respiratory symptoms and promptly arrange radiographic
      examinations, and to stop gefitinib treatment and begin glucocorticosteroid
      therapy whenever pulmonary toxicity is highly suspected.

PMID- 15850070
TI  - Spontaneous pregnancy and partial recovery of pituitary function in a patient
      with Sheehan's syndrome.
AB  - Sheehan's syndrome is caused by pregnancy-related hemorrhage leading to ischemic
      necrosis of the anterior pituitary gland and hypopituitarism. Spontaneous
      pregnancy in Sheehan's syndrome is very rare. We report the case of a patient
      with Sheehan's syndrome who suffered from anterior pituitary insufficiency, but
      with sparing of gonadotropic function. The patient became pregnant spontaneously
      and, after her second delivery, thyrotropic function recovered. However, the
      patient's growth hormone and cortisol levels remained unresponsive to an insulin
      tolerance test. This case demonstrates that pituitary function may recover from
      less extensive pituitary ischemia. We emphasize the importance of early
      identification of pregnancy in such cases. It is crucial to institute adequate
      hormone-replacement therapy during pregnancy, since hypopituitarism is associated
      with high fetal and maternal morbidity and mortality.

PMID- 15850071
TI  - Candidal arthritis after complete treatment of systemic candidiasis.
AB  - Over the last few decades, the incidence of invasive candidal infections in
      neonatal intensive care units has increased dramatically. Various complications,
      such as arthritis, endocarditis, meningitis, and endophthalmitis, have been
      reviewed. We present the case of a premature infant with systemic candidemia.
      Arthritis was discovered 6 months after completion of amphotericin B therapy, and
      was successfully treated with oral fluconazole for 6 weeks. We conclude that long
      term follow-up is particularly important in patients with treated candidemia. To
      prevent complications, prolonged treatment with high-dose amphotericin B is
      suggested for systemic fungal infection, and oral fluconazole is an effective
      alternative for candidal arthritis.

PMID- 15850072
TI  - Computed tomographic appearance of internal herniation through the sigmoid
      mesocolon.
AB  - The case of a patient with surgically proven internal herniation of a loop of
      ileum through the sigmoid mesocolon is described. This 66-year-old man presented
      clinically with acute lower abdominal pain and an elevated white blood cell
      count. A computed tomography (CT) scan showed a thickened bowel loop with "bird
      beak" appearance in the pelvis, centered towards the medial side and lying aside
      the effaced sigmoid colon. We think this CT picture is highly suggestive of
      internal herniation of the ileum through the sigmoid mesocolon, which is a rare
      clinical entity.

PMID- 15850073
TI  - Altering the mechanics of spider silk through methanol post-spin drawing.
AB  - Spiders have evolved to produce up to seven different silks; for each silk the
      balance between strength and elasticity is optimized according to the silk's
      specific use. Amino acid motifs have been identified and predicted functions have
      been assigned to these motifs. In addition to understanding the underlying
      molecular basis for structure/function relationships, it is also necessary to
      understand the contribution of the spinning process to the overall mechanical
      properties for both native and synthetic silk fibers. It is hypothesized that the
      natural silk fiber is produced through a process that involves dehydration.
      Current artificial spinning methods attempt to reproduce the natural dehydrating
      conditions by pulling the newly formed fiber through a methanol (or other
      dehydrating solvent) bath. However, the consequences of this treatment on the
      mechanical properties of the artificial fiber in relation to the natural fiber
      are unknown. To evaluate the effect of methanol on fiber properties, mechanical
      testing was done on native fibers from Nephila clavipes. Single major ampullate
      fibers were spun either in 47% ambient humidity or drawn post-spinning through a
      methanol bath. A comparison of the mechanical properties of the silk fibers
      revealed that post-spin drawing of a single major ampullate silk fiber through a
      methanol bath correlates to changes in the mechanical properties of the fiber.

PMID- 15850074
TI  - Support torques during simulated sit-to-stand movements.
AB  - Sit-to-stand movements are a fundamental daily activity and a prerequisite to
      upright posture. Previous simulations of spinal cord injured individuals using
      functional neuromuscular stimulation (FNS) suggested a forward foot placement
      would reduce hand-support forces. However, this recommendation has proved to be
      difficult for able-bodied individuals standing hands-free and for individuals
      with spinal cord injuries standing with a walker. This inverse model is a step
      towards the goal of using forward simulations to determine efficient sit-to-stand
      strategies. Initial seated postures varied from 80-110 degrees of knee flexion
      and 90-120 degrees of hip flexion. Realistic progressions of lower extremity
      joint angles including development of linear momentum were created using sigmoid
      functions. These kinematic values were used to estimate the required resultant
      joint torques to complete sit-to-stand. Joint torque values that act to raise the
      body were combined to indicate sit-to-stand difficulty from different seated
      postures. A representative foot-forward placement (knee 80 degrees, hip 90
      degrees) resulted in a maximum combined torque of 544 Nm. In contrast, a
      representative foot-back placement (knee 110 degrees, hip 120 degrees) resulted
      in a maximum combined torque of 661 Nm. An intermediate seated posture (knee 97
      degrees, hip 90 degrees) produced the lowest maximum combined torque of 401 Nm (2
      Nm ankle plantarflexion, 201 Nm knee extension, 198 Nm hip extension). Foot
      forward placement required substantial ankle dorsiflexion torques. The most
      efficient strategy appeared to be combining a foot back placement with momentum
      generation using hip flexion. By generalizing the sit-to-stand model beyond FNS
      driven movements, further insight may be gained into other populations (i.e.,
      elderly).

PMID- 15850075
TI  - Monitoring femoral component installation using vibration testing.
AB  - With emerging minimally invasive surgical techniques in total hip arthroplasty,
      there has been anecdotal evidence of an increase in fractures associated with the
      insertion of the prosthesis into the femur. The diminished visibility associated
      with minimally invasive surgical techniques necessitates a greater emphasis on
      the surgeon's tactile and auditory senses. These senses are used to ascertain the
      femoral component position of maximum stability and interference fit, as well as
      to prevent further component impaction and subsequent fracture of the femur. The
      work described herein attempts to identify a means to supplement the surgeon's
      tactile and auditory senses by using damage identification techniques normally
      used in civil and mechanical structures to monitor the insertion process of the
      prosthesis. It is hypothesized that vibration characteristics of the impact
      process may be used intraoperatively to determine at what position the femoral
      component has reached appropriate interference fit and stability in the femur.
      Such information may be used to prevent further impaction of the femoral
      component past a threshold that could result in a periprosthetic fracture. A
      piezoelectric accelerometer and impact hammer will be used to monitor the impact
      process. The acceleration time history data were analyzed by using low and high
      pass filters to allow frequency analysis of the time history signals. This paper
      will summarize features derived from the measured data that will be used to
      develop an insertion process termination indicator.

PMID- 15850076
TI  - Analysis of stiffness reduction in varying curvature ankle foot orthoses.
AB  - Ankle foot orthoses (AFO) are often used for patients who cannot generate a
      strong enough extension moment at the knee to allow functional gait. Orthotists
      often cut out portions of the AFO around the malleoli in order to improve
      comfort. There has been some question as to how this affects the stress
      distribution around the orthosis, the fatigue performance of the device, and the
      AFOs stiffness. To examine this, three orthoses were constructed with differing
      curvatures cut out of the malleolar regions. Photoelastic coatings were placed on
      the most stiff and least stiff orthoses, and the stress distributions while
      wearing the device were examined. A fixture was created to test the orthosis, and
      the stress distribution while loaded in the fixture closely matched the
      distribution with actual wear. These orthoses were then tested in fatigue for
      500,000 cycles at 5 Hz in displacement control. Initial displacements were set to
      provide maximum loads of 45 lbs. The displacement settings for the stiffest
      orthosis were 0.4 to 0.6 inches of deflection; the load decreased from 44 lbs to
      28 lbs after the final cycle. The least stiff displacement varied from 1.3 to 1.5
      inches, and the load value changed from 46 lbs to 35 lbs. The data will be useful
      in guiding orthotists in building AFOs, particularly when shaving portions of the
      AFO for comfort. Excessive shaving may seriously degrade the performance of the
      device, especially after longer life cycles.

PMID- 15850077
TI  - Effect of floor slope and load carriage on standing posture.
AB  - Posture has been linked to low back pain and other ailments. While heeled shoes
      have been investigated, the effect of floor slope and load carriage on posture
      has received little attention. Therefore, the goal of this investigation was to
      assess these factors. Twenty-one men and 22 women (all healthy) of college age
      provided university-approved informed consent prior to participation. After
      familiarization, subjects stood motionless on the slope (facing up and down at 10
      degrees and 20 degrees as well as the level), then bent over picking up a milk
      crate from the floor (men = 25kg, women = 15kg), and returned to a motionless
      standing position with the crate at knuckle height. Six trials were performed in
      each condition with the last three averaged to produce representative results in
      both standing conditions for each slope. Right sagittal plane kinematics and
      surface EMG of the erector spinae and middle trapezius were recorded. A static
      inverse model calculated moments at L5/S1. Significant differences (p < 0.001)
      between standing with and without the load were observed in all variables (torso,
      hip, knee, and ankle angles, L5/S1 moment, and both muscle activities) except low
      back curvature (p = 0.217). Across the floor slopes, significant trends existed
      in the low-back, knee, and ankle angles when standing without the load (p <
      0.001) while the same parameters plus hip angle and L5/S1 moment were
      significantly different across floor slope with the load (p < = 0.026). In
      conclusion, both floor slope and load carriage should be considered when
      assessing ergonomic factors related to standing posture.

PMID- 15850078
TI  - Hands-free human computer interaction via an electromyogram-based classification
      algorithm.
AB  - A four-electrode system for hands-free computer cursor control, based on the
      digital processing of Electromyogram (EMG) signals is proposed. The electrodes
      are located over the right frontalis, the procerus, the left temporalis and the
      right temporalis muscles in the head. This system is meant to enable individuals
      paralyzed from the neck down (e.g., due to Spinal Cord Injury) to interact with
      computers using point-and-click graphic interfaces. The intention is to translate
      electromyograms derived from muscle contractions associated with specific facial
      movements into five cursor actions, namely: Left, Right, Up, Down and Left-click.
      This translation is accomplished by a digital signal processing classification
      algorithm that takes advantage of the divergent spectral nature of the EMG
      signals produced by the frontalis, temporalis, and procerus muscles,
      respectively. The effectiveness of the algorithm is evaluated by comparing its
      performance to that of a previously developed three-electrode EMG-based
      algorithm, using Matlab simulations. The results indicate that the algorithm
      classifies with great accuracy and provides a marked improvement over the
      previous three-electrode system.

PMID- 15850079
TI  - Adaptive and wavelet filtering methods for improving accuracy of respiratory
      measurement.
AB  - Respiratory activity is commonly measured by chest and abdomen bands using
      respiratory inductive plethysmography (RIP) or similar techniques. Such
      respiratory signals pose special challenges to adequate processing since the
      range of natural breathing frequencies is wide, and movement artifacts are common
      during periods of physical activity and even during sleep. Presented are novel
      linear and nonlinear signal processing algorithms that enable the decomposition
      of the range of artifact generated by non-respiratory sensor movement, enabling
      the respiratory component to be retrieved. We evaluated the performance of these
      techniques for improved processing of human respiratory signals. We demonstrate
      that, in contrast to conventional low-pass filters that attenuated higher
      frequency breathing and swift respiratory events such as cough episodes, a soft
      thresholding technique applied to a set of wavelet filterbanks effectively
      denoised the signal without attenuating respiratory information. Another type of
      artifact, low frequency noise generated from walking or running motion, can
      appear as breathing at the pace frequency making it difficult to differentiate a
      breath from a heel strike. Since this artifact often resides in the respiratory
      frequency band it cannot be removed by classical or wavelet filtering methods. We
      introduce an adaptive filtering technique that uses an upward body acceleration
      signal as a reference to resolve the respiratory component. A real-life data set
      acquired with a novel ambulatory and sleep monitoring system (LifeShirt,
      VivoMetrics, Inc., Ventura, CA, USA) demonstrates the utility of these
      respiratory filtering approaches and indicates that accurate respiratory volume
      and timing information can be collected noninvasively in physically active
      subjects in- and outside the laboratory or clinic.

PMID- 15850080
TI  - Understanding blood pressure variability: spectral indices as a function of
      gender and age.
AB  - Typically, blood pressure variability has been calculated by taking the simple
      mathematical standard deviations of a collection of discrete blood pressure (BP)
      measurements. Recently, spectral analytic techniques have been employed to
      examine beat-to-beat blood pressure variability and the underlying autonomic
      adjustments associated with the performance of various tasks. In the present
      study, beat-to-beat blood pressure was examined in 104 older African-Americans
      males and females who were part of the Healthy Aging in Nationally Diverse
      Longitudinal Samples (HANDLS) Study. Participants evaluated faces and sentences
      depicting emotional content and rested before (Baseline) and after (Recovery) the
      tasks. There were no significant gender effects in any analyses. In addition,
      there were no significant task effects. However, there was a trend for both low
      and high frequency systolic blood pressure variability to decrease linearly from
      baseline, through faces and sentences to recovery. Interestingly, both systolic
      and diastolic high frequency blood pressure variability was greater in older as
      compared to younger adults. Increased blood pressure variability has been
      associated with greater sheer stress and greater end organ damage. These results
      will explicate the effects of aging on cardiovascular disease risk. Overall,
      these data indicate that blood pressure variability derived via spectral analytic
      techniques is a useful tool for understanding cardiodynamics and may provide a
      more in-depth analysis of blood pressure response.

PMID- 15850081
TI  - Transfer function analysis of gender-related differences in cerebral
      autoregulation.
AB  - Effects of gender in cardiovascular regulation are widely investigated, however
      differences in cerebral autoregulation (CA) between genders remains less
      explored. In the present study, we used spectral analysis to analyze differences
      in cerebral autoregulation between 10 men and 10 age-matched women. Subjects
      rested in a supine position (20 min) and then were passively tilted to a 70
      degree head up tilt position (30 min). During the first 10 min of supine they
      breathed only room air (Supine Control) while during the second 10 min of supine
      they breathed room air or room air plus 5% CO2 in a Pseudo Random Binary Sequence
      (PRBS) (Supine PRBS). During the first 10 min of tilt, subjects breathed room air
      or room air plus 5% CO2 switched in a PRBS (Tilt PRBS). For the remaining 20 min
      of tilt, they breathed only room air (Tilt Control). Blood pressure (BP) and
      cerebral blood flow velocity (CBFV) were non-invasively recorded using Finapres
      and Transcranial Doppler. Coherence and transfer function between mean BP and
      mean CBFV were estimated. During Supine Control, women had higher coherence (p <
      0.05) and transfer function gain (p < 0.01) within 0.03-0.10 Hz and 0.22-0.31 Hz
      than men. During tilt, coherence within 0.05-0.26 Hz were higher in men than in
      women (P < 0.02). Although the reasons for these gender-related differences in
      cerebral autoregulation remain unclear, our results suggest that in investigating
      cerebral autoregulation, gender may need to be considered as a factor.

PMID- 15850082
TI  - Evaluation of the male reproductive organs after treatment with continuous
      sustained delivery of statin for fracture healing.
AB  - The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors
      (statins) are widely used for the treatment of hyperlipidemia, and recent in
      vitro and animal data suggest that statins promote bone formation and increase
      bone strength. We examined the relationship between sustained continuous delivery
      of statin and fracture healing rates in adult male animals with femoral segmental
      fractures. Because statin affects the production of cholesterol we also evaluated
      the influence of statin, on adrenal and testicular steroidogenesis and the
      morphology of the reproductive tract tissues in animals receiving statin for a
      period of 12 weeks post surgery. Simvastatin significantly increased fracture
      healing and without significant influence on the body weights and the weights of
      the reproductive organs. Basal plasma LH, FSH and testosterone levels were not
      affected by active treatment with simvastatin. Reproductive tissue morphology was
      unchanged by local sustained release of statin. In conclusion, long-term
      simvastatin treatment delivered at a fracture target site did not influence
      testicular reproductive and endocrine function, but was able to effectively heal
      complicated segmental fracture.

PMID- 15850083
TI  - The metabolic effect of thyrotropin releasing hormone (TRH) and norepinephrine
      (NE) in cold-acclimated obese rats.
AB  - We have studied the effects of chronic peripheral infusion of thyrotropin
      releasing hormone (TRH) and norepinephrine (NE) alone and together. Do these
      hormones additively affect energy balance and body weight similarly in obese
      animals? 20 obese (fa/fa) Zucker strain rats were studied. Food intake, body
      weight and resting metabolic rate (RMR) were measured over a 14 day period. We
      confirmed that in these animals NE stimulated RMR, but with parallel stimulation
      of appetite so that weight gain continued; TRH stimulated RMR but inhibited food
      intake so that rate of weight gain was reduced. TRH and NE together acted to
      further enhance RMR, but the inhibitory and stimulatory effects on food intake
      cancelled out. Thus a negative energy balance resulted in this group of animals;
      however, resultant weight loss was moderate in obese compared to previously
      studied lean animals. We suggest that the relative insensitivity of the obese to
      TRH and NE together reflects the inability of their brown adipose tissue to
      respond to thermogenic agents, even when chronically administered.

PMID- 15850084
TI  - The role of route of estrogen adminstration on the proliferation of SiHa cells in
      culture.
AB  - The specific objectives of this investigation were: (1) to evaluate the effect of
      estrogen on SiHa cervical cells delivered by TCPL delivery system versus
      conventional administration as a model for cervical cancer intervention and (2)
      to determine the estrogen dose effect on proliferation of these cells in culture.
      Estrogen was delivered for three time periods, 24, 48, and 72 hours both by
      conventional administration (direct administration) and drug delivery system
      using TCPL ceramic capsules. Three dosages of estrogen were selected (2, 10, and
      100 pg/mL). Ceramic capsules were prepared using standard procedures (release
      profile 2, 10 or 100 pg/mL). Capsules were gas sterilized prior to being placed
      in the wells with cells. Data collected from this study indicated that,
      regardless of the route of administration, estrogen exposure did not induce major
      cellular injury at the 24 and 48 hour time period. Initially, there were various
      responses to estrogen among all groups compared to control. At 72 hours phase all
      experimental groups induced greater proliferation rate in the conventional
      delivery than in the groups exposed to sustained estrogen delivery. Low and
      medium doses conventionally added to the cells resulted in a decrease in cell
      number at 48 hours phase compared to the initial response at the 24 hours phase.
      With medium and high sustained delivery of estrogen rates, the data revealed that
      proliferation rate is directly proportional to duration of delivery compared to
      conventional means. The data suggest that the route of administration of estrogen
      is an instrumental tool in the prognosis of cervical cancer.

PMID- 15850085
TI  - Glomerular response to adrenocortical hormone alone or in combination with
      selenomethionine.
AB  - Increased levels of glucocorticoids (GC) can result in major complications such
      hypertension and vascular injury. Chronically, this condition may lead to
      impairment of renal function. Glucocorticoid excess was considered the etiologic
      agent that triggers over production of reactive oxygen species (ROS). The mode of
      action of ROS was implicated to disrupt nitric oxide availability in the vascular
      endothelium, leading to vascular complications. To circumvent this damage
      attempts were made to use antioxidants in order to counter-balance the oxidative
      process. The objectives of this study were: (1) to establish an animal model of
      increased glucocorticoid levels by sustained delivery and (2) to determine if
      sustained delivery of selenomethionine in combination with glucocorticoids could
      protect kidney tubular structures using adult rats. Sixteen female rats were
      divided into four equal groups (control and 3 experimental groups implanted with
      tricalcium phosphate lysine drug delivery systems (TCPL) charged with either 50mg
      selenomethionine (Se), 50 mg corticosterone (C), or 50 mg of both C and Se). At
      the end of 24 days, the rats were sacrificed and both kidneys were removed for
      histopathological analysis. Quantitative analysis was performed on serum calcium
      levels, body weights and kidney weights in animals from all groups. Kidney slides
      were screened for possible structural damage. Sustained release of Se and Se+C
      resulted in a significant reduction of glomerular area (p < 0.05). Data obtained
      indicated that C, Se and Se+C administration caused a reduction in serum calcium
      levels compared to control animals. The reduction may be in part to changes in
      calcium-filtered load, changes in glomerular filtration rates or interference of
      calcium absorption from the gut. In conclusion, data obtained from this
      investigation provided the literature with significant information regarding the
      role of sustained delivery of supraphysiological levels of corticosterone in
      modifying kidney structure and function (possibly alter blood pressure).

PMID- 15850087
TI  - New mechanism for inducing closed head injury in the rat.
AB  - Due to the frequency of closed head injuries and cost of treatment, there is
      great interest in the mechanical parameters involved in provoking the injury. A
      new device has been developed to produce closed head injury due to impact-induced
      angular acceleration in the rat. A 488-gram mass was propelled down a 2-meter
      drop tube by springs at a velocity of 21 mph (9.5 m/s), depending on strength and
      displacement of the springs. The projectile then impacts a lever arm protruding
      laterally from an aluminum helmet fixed at the anterior face with a ball-bearing
      pivot allowing only lateral rotation, which has been shown to cause severe brain
      injury. A sodium silicate elastomeric material with a thickness of 1 cm was
      placed at the impact interface to increase the contact time between the
      projectile and the lever arm. Biomechanical results from a lumped parameter
      mathematical model and testing indicated an angular acceleration of 300,000 +/-
      20,000 rad/s2, angular velocity of 300 +/- 50 rad/s, and impact duration of 2.0
      +/- 0.3 ms. When scaled to the human, the results indicated an angular
      acceleration of 4,100 rad/s2, angular velocity of 32 rad/s, and impact duration
      of 20 ms, consistent with values associated with classical concussion. Magnitudes
      and durations at these levels have not been produced in the rat by rotational
      loading caused by impact, and due to the flexibility of the design, these
      parameters can be further increased.

PMID- 15850086
TI  - Sustained release of OP-1 and antibiotics in treatment of femoral defects in male
      rats.
AB  - Osteogenic proteins (OP-1) promote osteoinduction. Formation of new bone growth
      in patients receiving OP-1 is not consistent, and is possibly due to the short
      half-life of the drug. In order to test the capacity of OP-1 to consistently
      produce bone in a fracture model, a drug delivery system was developed to prolong
      the action of OP-1. Fifteen Sprague Dawley male rats were randomly divided into
      three equal groups; Animals in group 1 served as control. Animals in groups 2 and
      3 had a 5mm defect created in the left femur using a number six dental burr and a
      drug delivery capsule (TCPL) containing either antibiotic alone (sham) or
      antibiotic +OP-1. Body weights, blood, and X-rays were taken weekly. Femurs and
      organs were harvested 30 days post-op, and processed for histomorphometry. Data
      was analyzed using ANOVA and significant difference between the groups was
      determined using Student Newman Kuels (p < 0.05). The results showed complete
      bone healing in the OP-1 group with an evident callus formation. The osteoid
      tissue exhibited a proliferation of osteoblasts, which differentiated from the
      vascularized mesenchymal tissue. The complete bone healing using OP-1 sharply
      contrasted sham treatment, where an obvious injury was still seen at 30 days.
      Histologically sham animals exhibited the early stage of repair with evidence of
      blood clotting and mesenchyme with early formation of osteoblasts. Overall, OP-1
      delivered in a sustained manner for 30 days caused increased bone formation in a
      defect model.

PMID- 15850088
TI  - Comparison of tail-suspension and sciatic nerve crush on the musculoskeletal
      system in young-adult mice.
AB  - Musculoskeletal unloading and disuse result in significant muscle and bone loss.
      These phenomena can be modeled using sciatic nerve crush or tail-suspension.
      Mature animals eliminate the complication of growth superimposed on bone and
      muscle loss. In the current study, young-adult (12-week old male) C57BL/6J mice
      were subjected to sciatic nerve crush (NC; n = 9) or tail-suspension (TS; n = 9)
      for 14 days, with a normal ambulatory control (n = 10). The soleus,
      gastrocnemius, and EDL muscles were collected and weighed at sacrifice. Femurs
      were analyzed in three-point bending for stiffness, elastic force and maximum
      force. Muscle masses in tail suspended mice were reduced by 41.9% (p < 0.001),
      17.5% (p < 0.001), and 9.1% (N.S.) for the soleus, gastrocnemius, and EDL,
      respectively. In NC mice, muscle masses were reduced by 18.6% (p = 0.004), 37.2%
      (p < 0.001), and 22.5% (p = 0.003). Femur stiffness, elastic and maximum forces
      were reduced by 20.9% (p = 0.014), 14.7% (N.S.), and 11.6% (N.S.) in TS, compared
      to NC where masses were reduced by 15.5% (p = 0.022), 0.2% (N.S.) and 11.2%
      (N.S.) in the crushed leg compared to the contralateral control. NC resulted in a
      greater reduction of muscle mass in the gastrocnemius and EDL muscle; whereas
      tail-suspension had a greater effect on the soleus. Tail-suspension had the
      greatest effect on bone mechanical properties. When comparing these results to
      actual spaceflight data, it appears as though TS most closely models muscle loss,
      and NC most closely models changes in bone mechanical properties. These unloading
      models have tissue-specific effects that impact their applications for
      musculoskeletal research.

PMID- 15850089
TI  - The effect of roof strength on reducing occupant injury in rollovers.
AB  - Roof crush occurs and potentially contributes to serious or fatal occupant injury
      in 26% of rollovers. It is likely that glazing retention is related to the degree
      of roof crush experienced in rollover accidents. Occupant ejection (including
      partial ejection) is the leading cause of death and injury in rollover accidents.
      In fatal passenger car accidents involving ejection, 34% were ejected through the
      side windows. Side window glass retention during a rollover is likely to
      significantly reduce occupant ejections. The inverted drop test methodology is a
      test procedure to evaluate the structural integrity of roofs under loadings
      similar to those seen in real world rollovers. Recent testing on many different
      vehicle types indicates that damage consistent with field rollover accidents can
      be achieved through inverted drop testing at very small drop heights. Drop test
      comparisons were performed on 16 pairs of vehicles representing a large spectrum
      of vehicle types. Each vehicle pair includes a production vehicle and a vehicle
      with a reinforced roof structure dropped under the same test conditions. This
      paper offers several examples of post-production reinforcements to roof
      structures that significantly increase the crush resistance of the roof as
      measured by inverted drop tests. These modifications were implemented with
      minimal impact on vehicle styling, interior space and visual clearances. The
      results of these modifications indicate that roof crush can be mitigated by
      nearly an order of magnitude, as roof crush was reduced by 44-91% with only a 1
      2.3% increase in vehicle weight. Additionally, this paper analyzes the glazing
      breakage patterns in the moveable tempered side windows on the side adjacent to
      the vehicle impact point in the inverted drop tests. A comparison is made between
      the production vehicles and the reinforced vehicles in order to determine if the
      amount roof crush is related to glazing integrity in the side windows. Lastly,
      two drop test pairs, performed with Hybrid III test dummies, indicates that the
      reduction of roof crush resulted in a direct reduction in neck loading and
      therefore an increase in occupant protection.

PMID- 15850090
TI  - Biomechanical analysis of occupant kinematics in rollover motor vehicle
      accidents: dynamic spit test.
AB  - A better understanding of occupant kinematics in rollover accidents helps to
      advance biomechanical knowledge and to enhance the safety features of motor
      vehicles. While many rollover accident simulation studies have adopted the static
      approach to delineate the occupant kinematics in rollover accidents, very few
      studies have attempted the dynamic approach. The present work was designed to
      study the biomechanics of restrained occupants during rollover accidents using
      the steady-state dynamic spit test and to address the importance of keeping the
      lap belt fastened. Experimental tests were conducted using an anthropometric 50%
      Hybrid III dummy in a vehicle. The vehicle was rotated at 180 degrees/second and
      the dummy was restrained using a standard three-point restraint system. The lap
      belt of the dummy was fastened either by using the cinching latch plate or by
      locking the retractor. Three configurations of shoulder belt harness were
      simulated: shoulder belt loose on chest with cinch plate, shoulder belt under the
      left arm and shoulder belt behind the chest. In all tests, the dummy stayed
      within the confinement of the vehicle indicating that the securely fastened lap
      belt holds the dummy with dynamic movement of 3 1/2" to 4". The results show that
      occupant movement in rollover accidents is least affected by various shoulder
      harness positions with a securely fastened lap belt. The present study forms a
      first step in delineating the biomechanics of occupants in rollover accidents.

PMID- 15850091
TI  - Subcatastrophic failure characteristics of the porcine descending aorta.
AB  - Failure of internal arterial layers prior to overall catastrophic vessel failure
      has been clinically documented and has significant clinical implications. For
      example, intimal failure of the internal carotid artery was associated with
      extremely high rates of morbidity (40-80%) and mortality (up to 40%). However,
      failure of internal vessel layers prior to catastrophic vessel failure has been
      experimentally documented in a limited number of studies and the mechanical
      relationship between initial and ultimate vessel failure has not been
      systematically explored. In the present investigation, seven porcine descending
      aorta specimens were mechanically tested using a novel protocol to quantify
      failure of internal layers relative to overall vessel failure. The protocol
      consisted of opening the vessel at the mid-diameter level, mechanically
      distracting the vessel to failure under quasi-static loading, and imaging the
      event from intimal and adventitial sides using a high-speed, high-resolution
      digital imaging system. The internal layer failed prior to catastrophic vessel
      failure in all specimens. Adventitial (outer) layers remained intact until
      ultimate failure. Initial internal layer subfailures occurred at 88% of the
      strain to ultimate failure. The present results demonstrate internal layer
      susceptibility to subcatastrophic failure without overall failure of the vessel.
      Although the porcine descending aorta may not be particularly susceptible to
      distraction failure, this vessel may be a suitable model for human arterial
      tissue due to similarities in geometric size and vessel structure.

PMID- 15850092
TI  - Stimulation of fracture healing by continuous delivery of demineralized bone
      matrix proteins and tobramycin.
AB  - Demineralized bone matrix (DBM) is an allogenous, bioabsorbable material that has
      long been used for its osteoinductive and osteoconductive properties. A
      significant complication experienced by physicians who perform bone defect
      filling surgery is the risk of subsequent bacterial infections and the
      inefficiency of oral antibiotics to provide adequate prophylaxis against
      microorganisms, especially Staphylococcus aureus, Pseudomonas aeruginosa, and
      Staphylococcus epidermidis. In order to deliver both DBM and an efficient
      antiobiotic at high local concentrations without deleterious systemic effects, a
      ceramic sustained delivery system was implanted and monitored over the course of
      30 days for bone regeneration, infection, and systemic effects. Twenty-five adult
      Sprague Dawley albino male rats were used in the experiment. They were randomly
      divided into five equal groups. Animals in group 1 were used as control, group 2
      animals had a created 5mm defect, in group 3 defect induced and implanted with
      devices loaded with antibiotic (tobramycin) alone, group 4 had a created defect
      plus DBM, and group 5 had a created defect, plus tobramycin (which is effective
      against the aforementioned organisms) and DBM. At 30 days post-implantation, the
      experimental animals showed no significant difference in weight when compared to
      the control and sham animals. X-rays taken at this time showed the experimental
      femurs to be totally healed and virtually indistinguishable from control. Initial
      dissections revealed that the implants were accepted by the hosts as shown by the
      fibrous, vascularized sheath that surrounded the femurs and capsules. The
      implants were found to be in close contact with the cancellous bone and none of
      the sheaths showed signs of infection. Macroscopically, no defect could be
      detected in the experimental animals, while little regeneration was observed in
      the femurs of the sham animals.

PMID- 15850093
TI  - Exercise prevention of unloading-induced bone and muscle loss in adult mice.
AB  - Skeletal unloading causes bone and muscle loss that may be reversed by post
      unloading exercise. This study examines the effects of unloading and exercise,
      using tail-suspension for 14 days combined with a week of post-suspension cage
      wheel running in mice. Twenty-four adult, male, C57BL/6J mice were divided into
      four groups (n = 6 mice/group); unsuspended non-running, tail-suspended non
      running, unsuspended running, and tail-suspended running. At sacrifice, the calf
      (soleus, gastrocnemeius and plantaris complex), heart, tibia and femur were
      collected and weighed. The femora and tibiae were cleaned of non-osseous tissue,
      subjected to 3-point bending (femurs only), and weighed for dry (105 degrees C;
      24h) and ash mass (800 degrees C; 24h). The mean calf mass from the tail
      suspended groups (157.13 +/- 2.83 mg) was significantly less than in the
      unsuspended groups (167.33 +/- 2.83 mg; p = 0.019), with no significant effect of
      cage wheel running. The mean heart mass in running groups (166.58 +/- 4.78 mg)
      was significantly greater than the non-running groups (148.17 +/- 4.78 mg; p =
      0.013), with no effect of hindlimb suspension. The mean femur ash mass from tail
      suspended groups (24.02 +/- 0.38 mg) were significantly less than the unsuspended
      groups (25.11 +/- 0.34 mg; p = 0.050), and the running groups (25.13 +/- 0.38 mg)
      were significantly greater than the non-running groups (24.00 +/- 0.34 mg; p =
      0.043). No effect was observed for the femur dry mass or percent mineralization.
      Measurements of mechanical length tended to be lower in tail-suspension, with no
      significant affects do to cage wheel running. This study suggests that tail
      suspension in adult mice significantly decreases skeletal muscle and bone mass,
      with no change in percent mineralization. Furthermore, one week of running does
      not reverse the effects on the skeletal muscle and bone mass.

PMID- 15850094
TI  - The effect of agonists and antagonists on Hep-2 cells.
AB  - Androgens may play an important role in promoting the growth of laryngeal
      carcinomas. The aims of this investigation were to investigate the effects of
      (testosterone (T) and androstendione (AED)) in the presence of the anti-androgen,
      spironolactone (S), n Hep-2 cellular proliferation and damage after 24, 48 and 72
      hours. Hep-2 cells were divided into six groups (n = 5) control, S, T, AED, S+T,
      and S+AED, respectively. The cells were harvested after each incubation period
      into two different fractions: suspended cells and adhered cells. Cell counts and
      cellular damage determinations were performed on each fraction. Analysis of
      variance was used to determine significance at p < 0.05. Data for cell counts
      revealed an interesting phenomenon between the two fractions. Adhered cells
      showed decreased cell numbers in the presence of S and T for 24 - 48 hours
      followed by a significant increase at 72 hours. Cells in the adhered fraction
      incubated in the presence of AED or AED + S were significantly lower for the
      duration of the experiment. However AED or AED + S treatment caused significant
      increase in cell number in suspended fraction for the duration of the experiment.
      All treatments after 72 hours showed a slight reduction in MDA levels indicating
      treatments did not cause cell damage. Overall, the data suggests the possibility
      of two populations of cells that respond differently to the AED. T had no
      significant effect on either cell fraction for the first 48 hours followed by a
      significant increase in cell number at 72 hours suggesting T may need to be
      converted enzymatically to the more potent androgen, dihydrotestosterone.

PMID- 15850095
TI  - The role of proteoglycans in idiopathic carpal tunnel syndrome.
AB  - Decompression of the carpal canal is the most common hand surgery performed in
      the United States. Hand surgeons perform 460,000 carpal tunnel releases (CTR)
      each year, which cost the medical industry in excess of two billion dollars per
      year. The focus of this investigation was to identify the changes, which occur in
      the flexor tenosynovium of patients undergoing CTR at the connective tissue
      level. The connective tissues determine the amount and arrangement of
      macromolecules (fibers, proteoglycans, and glycoproteins) in the extracellular
      matrix. The proteoglycans are soluble macromolecules that have both structural
      and metabolic roles. Glycoproteins help to form the interstitial space, basement
      membrane and function as cell surface receptors. The mechanical function of the
      proteoglycans includes stabilization of the collagen fibers as well as function
      in the hydration of the tissues. It has been previous shown that changes in the
      oxygen concentration at the tissue level can alter the proteoglycans profile of
      the tissue. During periods of hypoxia, such as those obtained during repetitive
      motion CTS; the glycolytic pathway acts as the energy source for the tissue.
      Productions of chondroitin sulfates are a process consumes NAD and would be
      potentially toxic to the cells under anaerobic conditions. Production of keratan
      sulfate is NAD sparing product, and may act as a survival pathway for cells under
      adverse conditions. The disruption in the proteoglycan balance will allow for
      alterations in the ECM and changes in hydration status of the tissues may have
      serious implication in CTS because the carpal canal is anatomically very narrow
      and increases in volume within the canal can result in further compression of the
      nerve. Flexor tenosyioum was obtained from patients undergoing CTR and compared
      with control tissue for dermatan, keratan and chondroitin sulfate. The results
      show a greater density of keratan reactivity in CTS tissues identified by
      immunostaining. In addition to changes in proteoglycan content there was also an
      increase in new vessel formation in the CTS tissues. The data obtained suggests
      that the shifts in the proteoglycan ratios may render the tissues less able to
      withstand the compressive forces and therefore allow for more force to be placed
      on the median nerve within the carpal canal.

PMID- 15850096
TI  - University of Wyoming College of Engineering undergraduate design projects to aid
      Wyoming persons with disabilities, a mid-program review.
AB  - In Spring 2002 the University of Wyoming received National Science Foundation
      funding from the Division of Bioengineering and Environmental Systems to provide
      a meaningful design experience for University of Wyoming, College of Engineering
      students that will directly aid individuals with disabilities within the state of
      Wyoming. At the 2003 RMBS we presented a paper on the value of starting such a
      program. We have found that students receive a much richer capstone design
      experience when developing a project for direct use by a challenged individual.
      We are now approximately midway through this project. Since its inception the
      program has blossomed to include serving individuals in several regional states,
      outreach short courses to the community, projects have become of increasing
      difficulty and involve interdisciplinary teamwork, and many challenged
      individuals have been provided specialized one of a kind assistive devices. In
      this paper we will report on these advancements, lessons learned, and benefits
      received by participating in this vital program.

PMID- 15850097
TI  - Design parameters of a low flow rate sidestream capnograph.
AB  - The use of sidestream capnometers, with a sampling rate of 150-250 cc/min, as a
      means of measuring a patient's expired CO2 (ETCO2) and respiratory rate, has been
      a common practice for many years. However, in recent years, there has been a
      focus on lower flow rate sampling sidestream systems due to the benefits of less
      loss of tidal volume for patients, such as infants or neonates. When developing a
      sidestream system, four principle issues must be considered; 1) The signal
      fidelity of the gas sample must be sufficiently maintained from the sampling site
      to the measurement site. 2) Condensate from a patient's breath, as well as blood,
      mucus, or other contaminates often pose problems for sidestream systems and
      requires mitigation. 3) The mechanics of transporting a gas sample at a constant
      flow rate through the sampling system, regardless of atmospheric or clinical
      conditions must be developed. 4) The physics of handling CO2 gas throughout the
      transport process must be understood in order to ensure accurate readings. These
      issues lead to a complex web of interrelations that are explored in the
      development of a low flow rate sidestream capnometer.

PMID- 15850098
TI  - A web-based care-requiring client and Home Helper mutual support system.
AB  - For the improved efficiency of home care of the elderly, a web-based system has
      been developed to enable faster communications between care-requiring clients,
      their Home Helper and the care manager. Changes to care items, such as cooking,
      bathing, washing, cleaning and shopping are usually requested by the elderly
      client over the telephone. However, the care central office often requires 24
      hours to process and respond to such spoken requests. The system we have
      developed consists of Internet client computers with liquid crystal input
      tablets, wireless Internet Java enabled mobile phones and a central office server
      that yields almost instant communication. The care clients enter requests on the
      liquid crystal tablet at their home and then their computer sends these requests
      to the server at the Home Helper central office. The server automatically creates
      a new file of the requested items, and then immediately transfers them to the
      care manager and Home Helper's mobile phone. With this non-vocal and paperless
      system, the care-requiring clients, who can easily operate the liquid crystal
      tablet, can very quickly communicate their needed care change requests to their
      Home Helper.

PMID- 15850099
TI  - Frequency dependent hysteresis of silicone and latex mock arteries used in stent
      testing.
AB  - Mock arteries also called as mock vessels are one of the best alternatives
      available to researchers in evaluating the mechanical characteristics and
      durability of intravascular medical products without having to use animal and
      human clinical studies. The behavior of mock arteries depends on the frequency of
      loading. This makes it essential to evaluate and analyze the compliance and
      hysteresis of the mock arteries at different frequencies. Hysteresis, the
      difference in the pressure-volume curve between the loading cycle and the
      unloading cycle, plays an important role in determining the mechanical properties
      of the mock arteries. Six each of silicone and latex mock arteries were tested
      for this study. Three silicone and three latex mock arteries were tested at room
      temperature for dynamic internal compliance, and the remaining three each of
      silicone and latex mock arteries were soaked in distilled water at 37 degrees C
      for 36 hours and then compliance tested using a dynamic compliance tester. All
      arteries were tested at four different frequencies: 72, 500, 1000, and 1500 beats
      per minute.

PMID- 15850100
TI  - A bioinstrumentation system for the identification of EEG correlates of tinnitus.
AB  - Tinnitus is the spontaneous 'ringing' sensation within the auditory system
      reported by many individuals, which currently can only be diagnosed by behavioral
      response. Studies in this area have yet to identify definite mechanisms or sites
      associated with the generation of this sensation. The tinnitus sensation is
      typically reported to be prominent during silence. In addition, the complete
      withdrawal of auditory stimulus usually precedes the onset of the tinnitus
      sensation. This paper describes the conceptualization, integration and testing of
      an experimental instrument, developed to observe Auditory Evoked Potentials
      (AEPs) in order to identify possible EEG correlates of tinnitus. The instrumental
      setup permits the study of AEP responses during silence, as well as to observe
      the transitional nature of the AEP.

PMID- 15850101
TI  - Biomimetic machine vision system.
AB  - Real-time application of digital imaging for use in machine vision systems has
      proven to be prohibitive when used within control systems that employ low-power
      single processors without compromising the scope of vision or resolution of
      captured images. Development of a real-time machine analog vision system is the
      focus of research taking place at the University of Wyoming. This new vision
      system is based upon the biological vision system of the common house fly.
      Development of a single sensor is accomplished, representing a single facet of
      the fly's eye. This new sensor is then incorporated into an array of sensors
      capable of detecting objects and tracking motion in 2-D space. This system
      "preprocesses" incoming image data resulting in minimal data processing to
      determine the location of a target object. Due to the nature of the sensors in
      the array, hyperacuity is achieved thereby eliminating resolutions issues found
      in digital vision systems. In this paper, we will discuss the biological traits
      of the fly eye and the specific traits that led to the development of this
      machine vision system. We will also discuss the process of developing an analog
      based sensor that mimics the characteristics of interest in the biological vision
      system. This paper will conclude with a discussion of how an array of these
      sensors can be applied toward solving real-world machine vision issues.

PMID- 15850102
TI  - Selective protein adsorption on micro-textured P-type and N-type silicon wafers.
AB  - There has recently been a great deal of effort put towards the development of
      bioMEMS-based electrochemical biosensors for use in implantable devices.
      Currently, the primary issue limiting the lifespan of implantable sensors is
      protein and cell adhesion (biofouling) to the sensor surface, which impedes the
      sensor's access to analyte. To better understand this problem, it would be useful
      to have an understanding of how silicon-based microdevices interact with proteins
      in a physiological environment. To help answer this question, we investigated the
      interactions of proteins with microtextured silicon wafers. Bulk micromachining
      techniques were used to create micro-textures that varied between 5 and 80
      microns in size nd spacing. We used n-type and p-type silicon wafers with a <100>
      crystal orientation. Shapes such as rectangles, circles, and triangles were
      fabricated that were recessed into the silicon substrate. The features were
      estimated to be between 3 and 8 microns in depth. After the features were
      created, the wafers were coated with a layer of silicon dioxide. Once fabrication
      was complete, the wafers were incubated in vitro ith fluorescently tagged Albumin
      (500 microg/ml in Phosphate-Buffered Saline, PBS) for 5 minutes. The wafers were
      then rinsed with PBS solution and viewed using an epifluorescence microscope.
      Albumin adsorbed selectively onto the micropatterned wafers. Depending on the
      type of wafer we found that albumin adsorbed selectively onto either the bulk
      surface, the sidewalls, or the bottom of the etched feature.

PMID- 15850103
TI  - A photochemical microreactor used to analyze hydrogen peroxide (H2O2) production
      of T lymphocytes.
AB  - In this report we describe a new photochemical reactor and its use in the study
      of ultraviolet-B light (UVB) dependent H2O2 production by T lymphocytes. In the
      reactor multiple biological samples rotate around a luminescent tube and thus
      simultaneously absorb a uniform light-flux. The reactor was developed to expand
      our earlier studies where we showed that UVB activates T lymphocytes so that
      10(7) cells produce about 60 nmol H2O2 per minute. H2O2 has increasingly become
      recognized as a cell signaling molecule regulating immune reactions mediated by T
      lymphocytes. Our laboratory is researching the potential of such immune
      regulators as potential future therapeutic agents. To study photochemical H2O2
      production in small samples such as suspensions of T lymphocyte cultures or cell
      extracts, we designed a reactor in which 12 samples (each 50 - 500 microliters)
      can be exposed to light under temperature-controlled conditions. The samples are
      mounted on a rotating platform equidistant from the axis of rotation, where the
      light source of the photoreactor is located. Rotating the samples helps assure
      that all samples receive a uniform amount of light energy over time. A cooling
      fan is integrated in the base of the reactor to help minimize convective heat
      transfer between the lamp and the samples. We simultaneously operate two
      identical systems to be able to compare data that are obtained from light exposed
      samples under control and experimental conditions. Data on the influence of
      therapeutically relevant electromagnetic fields on H2O2 production of T
      lymphocytes are presented. H2O2 was quantified using the Amplex Red dye.

PMID- 15850104
TI  - Catheter-tip sensor to monitor production of hydrogen peroxide in small
      biosamples.
AB  - Recently, it was shown that antibodies in the presence of ultraviolet (UV) light
      give rise to singlet oxygen which ultimately leads to the production of hydrogen
      peroxide (H2O2). In this research, we are interested in understanding the role of
      H2O2 in T-cell activity during inflammation. Since the T-cell receptor has been
      shown to have the same oxidative catalytic potential as antibodies, we started
      experiments measuring H2O2 production in antibodies and T cells. After showing
      that a positively polarized Clark oxygen electrode can be used in measuring H2O2
      production in antibodies and T-cells, it is the goal of the current study to
      characterize the use of a catheter-tip sensor under similar conditions. Our
      catheter has a platinum ring which acts as the anode and a silver/silver chloride
      tip which acts as the cathode. Although this newly designed amperometric
      biosensor works on the same principles of electrochemistry, its compact size
      equips us with the potential for in vivo use and small sample testing. Operating
      at a polarizing voltage of 0.7 Volts v/s Ag/AgCl, the bare sensor produced a
      current of 8 +/- 2 nA per microM H2O2 with a 10 seconds response time, over a
      range of 0-50 microM H2O2. For use with biosamples, we added a hydrophilic H2O2
      permeable membrane, which reduced the electrode current to 0.48 +/- 0.1 nA/microM
      H2O2 and increased the response time to 2 minutes. On the other hand, the
      addition of the membrane improved the signal to noise ratio and the selectivity
      of the sensor. Using this sensor, we reproduced the light mediated H2O2
      production which was recorded at the rate of 20 nM per minute for 1 milliliter of
      6.7 microM rat IgG solution. We further discuss the usefulness, limitation and
      the future scope of this real time monitoring system for H2O2 research using
      small biosamples.

PMID- 15850105
TI  - The effects of genistein concentrations on Hep-2 cellular function.
AB  - Genistein is a phytoestrogen that has shown potential as a chemotherapeutic
      agent, which acts by inhibiting protein-tyrosine kinase and topoisomerase II
      enzymes. These particular enzymes are crucial for cellular proliferation. The
      goal of this study was to evaluate the effect of genistein concentration (0.5,
      0.05 or 0.005 mg/mL) on Hep-2 cells functional capacity. Specifically, to
      evaluate cellular number, protein, damage and morphology at 24, 48, and 72 hours
      phases. Data obtained from this study revealed that cell numbers were
      significantly reduced in low and medium concentrations after 24hrs, and cell
      numbers appeared to rebound at 48 and 72hrs in an inverse fashion. This data
      suggests continuous administration of the drug at therapeutic levels would serve
      as a better chemotherapeutic agent. Cellular damage was not evidenced and
      suggesting that the drug did not target the cellular membrane site. Morphological
      changes such as anucleation were seen at 24 hrs in all doses suggesting that
      genistein targets the genome directly. Interestingly, cellular function was able
      to recover in the lower doses of genistein treatment indicating cellular
      metabolism of the drug. Also, this information suggests that genistein mode of
      action by targeting enzymatic activity, as opposed to causing alterations within
      the cellular membrane, leading to leakage of cellular contents and ultimately
      cellular death since the membrane did not show evidence of lipid peroxidation.

PMID- 15850106
TI  - Growth and cell viability of estradiol and IP-6 treated Hep-2 laryngeal carcinoma
      cells.
AB  - Inositol 6-phosphate (IP-6) has demonstrated novel anti-cancer activity using
      several different tumor models. IP-6, a phytoestrogen, has estrogen receptor (ER)
      binding capabilities that are not known to cause cellular proliferation in
      hormone sensitive cells. It is hypothesized that IP6 can induce competitive
      inhibition with estrogen for estrogenic binding sites on cancer cells resulting
      in decreased proliferation. In this experiment, Hep-2 cells were treated with
      Estradiol and IP-6 in a dose dependant manner for 24, 48, and 72 hours. They were
      analyzed for changes in number, protein concentrations, damage, and morphology.
      There was an increase in cell proliferation in Estradiol treated Hep-2 cells.
      Cells treated with IP-6 showed no change in cell proliferation in the 24 or 48
      hour groups, but there was a decrease in number with the 72-hour group,
      particularly with the 1mM dose. Both the Estradiol and IP-6 treatments caused no
      membrane oxidation and the level of protein synthesis stayed consistent. The
      morphology showed small round to cuboidal, single cells with scant, dense,
      basophilic cytoplasm and hyperchromatic nuclei with smooth borders. Some cells
      showed anucleation and cellular degeneration. Although IP-6 is a phytoestrogen,
      the results show that affinity for estrogen binding sites on Hep-2 cells is
      greatly decreased. However, with time given increased concentrations, IP-6 can
      cause a decrease in the cellular proliferation of Hep-2 cells without initiating
      cellular apoptosis.

PMID- 15850108
TI  - Evaluation of insulin-like growth factor-1 and parathyroid hormone on growth
      characteristics of MG-63 cells.
AB  - Insulin-like Growth Factor-1 (IGF-1) and Parathyroid hormones (PTH) are major
      endocrine secretions that contribute to bone formation. The purpose of this
      experiment was to examine MG-63 bone like cells after treatment with PTH and IGF
      1 in low (1 ug), medium (5 ug), and high (50 ug) dosage levels. MG-63 cells were
      plated onto a 24 well tissue culture plate at a density of 1 x 1--5 cells per
      well. The experiment was designed to evaluate cell counts, cell damage (MDA),
      protein levels, calcium levels, alkaline phosphatase levels, and cellular
      morphology after 24, 48, and 72 hours post incubation with IGF-1 and PTH. Both
      hormones stimulated cellular mitotic division as evidenced by morphology and cell
      numbers. There was an inverse relationship between dose and cell number with the
      lower dose of IGF-1 and PTH causing the most increase. In both hormones, the
      exposure to the highest dose induced the largest MDA level increase. However, in
      the protein levels, few changes in protein levels were found with IGF-1, but PTH
      showed an increase of protein levels over the time periods. Morphological
      evaluation showed prominent nucleoli and cellular division throughout both
      treatments, however the cells with IGF-1 became extremely elongated and the cells
      with PTH became rather plump. The information gathered suggests that IGF-1 and
      PTH have an anabolic effect on MG-63 and the effect is dose dependent with both
      treatments with the lower dose being more effective.

PMID- 15850107
TI  - The effects of isolated antioxidants from black seed on the cellular metabolism
      of A549 cells.
AB  - Reactive oxygen species cause cytotoxic effects. The body requires the uptake of
      exogenous compounds with antioxidant potential. Black seed (BS) is a plant that
      contains at least one active lipid soluble antioxidant, thymoquinone.
      Fractionation of the seed components yielded antioxidant compounds in both the
      water soluble and lipid soluble fractions. The objective of the study was to
      determine the safety of the fractionated compounds and compare their potency with
      pure thymoquinone and vitamin E on A549 cells in culture for 24, 48 and 72 hours.
      RESULTS: Black seed extracts and pure thymoquinone showed markedly reduced levels
      of MDA for the duration of the study. The vitamin E dosage used led to greater
      toxicity and cellular damage rather than cell protection. Cellular proteins
      levels after 24 hours showed cells in BS + ETOH extract group had the highest
      metabolic activity. However, at 72 hours, the activity was shifted and showed the
      least amount of protein synthesis. As for vitamin E, the results were consistent
      throughout all three phases showing slow metabolic activity. Cell number was
      decreased after 24 hours in thymoquinone treated cells, and remained reduced for
      the duration of the study. The BS+H2O fraction showed a similar trend to
      thymoquinone, where as the BS+ETOH fraction showed a negative shift in cell
      number at 48 hours when compared with the control. CONCLUSION: The study
      concludes that of the two BS extracts, the BS+H2O extract had the greatest effect
      on the cell viability and function.

PMID- 15850109
TI  - Pathophysiological response of rhesus monkey kidney epithelial cells exposed to
      epigallocatechin-3-gallate.
AB  - Green tea extracts are obtained from Camellia sinensus leaves that have been
      dried and contain the polyphenol known as catechins (epigallocatechin-3-gallate,
      EGCG). Green tea has been suggested to have an inhibitory effect on various
      complications such as HIV, cancer cells, homocysteine-related diseases, and
      cardiovascular disease. The literature is lacking on the role that green tea
      might have on normal cells that are at a high risk of irreversible injury. These
      cells include the lining of vessels (endothelium) and kidney tubules
      (epithelium). The specific objective of this study was to investigate the effects
      of various concentrations of green tea on the proliferation and viability of
      Rhesus Monkey Kidney epithelial cells (RMKEC) in culture. Thirty tubes were pre
      plated with RMKEC sub-divided into six equal groups. In-groups 1-5, tubes were
      treated with 20, 2, 0.2, and 0.002i M of active extract of green tea (EGOG),
      respectively. Data obtained suggests that: (1) at 24 hour phase, exposure to 20,
      2, and 0.0.2 microM concentrations induced cell proliferation and no significance
      difference was observed using 0.002 microM EGCG in comparison to the control, (2)
      at 48 hour phase, the use of 20 uM EGCG induced a proliferative effect in
      comparison to the control, (3) a decrease in cell proliferation was observed
      using a concentration of 2, 0.2, 0.002 microMEGCG in comparison to the control,
      (4) at 72 hour phase, there was a decrease in cell number in the groups treated
      with 20 and 2 microM concentrations of EGCG, (5) at 96 hour phase, there was a
      decrease in cell number in the group treated with the 0.002 microM concentration
      of EGOG, (6) RMK EC treated with EGCG at concentration of 0.2i M for 24, 48, 72,
      and 96 hours displayed a significant decrease in catalase, and MDA, (7) RMKEC
      treated with 0.002 for 48, 72, and 96 ours displayed an increase in MDA and
      catalase. The various concentrations of green tea affected Rhesus Monkey Kidney
      Epithelial cell growth, function, and viability; however, the data suggests that
      further studies need to be conducted to determine the full impact of green tea on
      Kidney Epithelial function.

PMID- 15850110
TI  - Software-based compensation of visual refractive errors of computer users.
AB  - For human beings, vision is one of the most important senses in interacting with
      the surrounding environment, as well as with any tools that require visual
      communication. As such, the ability to interact effectively with computers
      through typical graphic user interfaces (GUIs) is greatly affected by any
      refractive errors present in an individual's visual system. If the refractive
      errors can be mathematically modeled, a system for overcoming these aberrations
      can be devised which can increase the effective human-computer interaction for
      these individuals. Several methods, such as Adaptive Optics, have been proposed
      that attempt to solve this problem using electro-mechanical devices. These
      methods are costly and impractical, preventing most visually impaired individuals
      from benefiting from their use. In contrast, an image-processing method, based on
      deconvolution techniques, has recently been proposed for the pre-compensation of
      images to be displayed in a computer. This method is much more practical, being
      completely implemented in software, and has achieved encouraging results.
      Previous results have yielded an average 50% increase in visual efficiency in the
      compensation of a known artificial aberration introduced into the field of vision
      of experimental subjects. This paper describes the difficulties encountered with
      the present software-only compensation and proposes several methods for
      overcoming these obstacles. The difficulties, as well as the proposed solutions,
      are described theoretically and followed by examples using a lens system showing
      the improvement over previous methods.

PMID- 15850112
TI  - Firing rate relationship in the saccade system neural pathway.
AB  - This paper describes the relationship among the structures of the brain involved
      in the control of the saccadic system. The eye position information is pre
      processed by the cerebral cortex and then projected to the cerebellum where this
      signal is propagated to several structures that are in charge of the control and
      correction of the eye movement signal. Once this processing is completed, the
      output is propagated to the final neural stage (the motor neurons), and then to
      the Rectus and Oblique group of muscles of the eye. In our simulated model, the
      interaction of the different areas in this neural pathway and its feedback loops
      is shown through the correlation of the different firing rates of each structure,
      including background or spontaneous activity components. In order to improve
      portability the model is implemented with the Matrix Laboratory Language (MATLAB)
      and the Simulink toolbox.

PMID- 15850111
TI  - The segmentation and visualization of a neuron in the housefly's visual system.
AB  - Those studying biological systems are often interested in the morphology of the
      various microscopic organelles. The three dimensional reconstruction and
      visualization of objects provide a powerful tool to understand the nature of each
      object, and its relationship to other objects. Segmentation is the key to 3D
      analysis and study of objects that have been recorded with a series of sectioned
      images, such as from a confocal laser scanning microscope (CLSM). Segmentation is
      the process of completely separating or isolating the individual objects in an
      image. A seed-based semi-automatic segmentation tool has been developed to aid in
      the process of 3D visualization of objects recorded with serial sectioned images,
      including a boundary creation method that maintains the separate identity of
      contacting objects. This segmentation tool also allows the user to retain
      background information as a separate object, providing important reference and
      landmark information for the object of interest. This paper summarizes the main
      parts of the segmentation algorithm and presents 3D reconstructions of visual
      neurons of the housefly, Musca domestica. These reconstructions are compared to
      typical 3D images produced from other widely used software packages, including
      standard CLSM imaging software and the popular ImageJ supported by National
      Institute of Health (NIH). Efforts are underway to develop a user-friendly
      graphical user interface (GUI) for the segmentation algorithm to entice broader
      used in research settings.

PMID- 15850113
TI  - Simplest ever digital / analog neuron: "SEDAN-6".
AB  - The author continues with his series on artificial neuron construction. Using the
      smallest commercially available microcontroller, a 6-pin 8-bit unit, he has
      created several types of McCulloch-Pitts neurons and logic elements suitable for
      inclusion into various kinds of artificial neural networks. Additionally, by
      employing the on-chip analog comparator and simple off-chip stratagems, he has
      also implemented Hebb neurons and his android emotion emulator. These designs
      constitute the simplest artificial neurons which can be embodied using a
      microcontroller, and which are suitable for a wide variety of applications.

PMID- 15850114
TI  - Using parallel evolutionary development for a biologically-inspired computer
      vision system for mobile robots.
AB  - We describe a new approach to attacking the problem of robust computer vision for
      mobile robots. The overall strategy is to mimic the biological evolution of
      animal vision systems. Our basic imaging sensor is based upon the eye of the
      common house fly, Musca domestica. The computational algorithms are a mix of
      traditional image processing, subspace techniques, and multilayer neural
      networks.

PMID- 15850115
TI  - A design of multiagent-based framework for volume image construction and
      analysis.
AB  - This paper describes a design of a multiagent-based system that can be used to
      manage the acquisition and analysis of ultrasonograph images. The major concept
      is to design a management framework consisting of multiple intelligent agents to
      direct the ultrasonograph image acquisition and analysis operations carried out
      using a high-speed bit-parallel architecture efficiently as well as to allow for
      the construction of 3D images from 2D ones. Volume image operations need
      reactivity, autonomy, and intelligence of software. Therefore, agents can play an
      important role in enhancing the overall operation of medical image analysis. The
      system suggests a set of image analysis operations including smoothing, noise
      removal, and enhancing techniques. These operations will be implemented using
      parallel processing architectures while the management framework will consist of
      different agent types such as: simple reflex agents, agents that keep track of
      the world, goal-based agents, and utility-based agents. These agents interact
      with each other and exchange data among themselves in order to achieve a
      comprehensive speed in performing the volume image construction operations.
      Guided with the fact that the agent consists of program and architecture, the
      system deploys parallel processing architectures to implement the image analysis
      operations. The system is considered a step towards a complete multiagent-based
      framework for medical image acquisition and analysis.

PMID- 15850116
TI  - Modeling human behaviors and reactions under dangerous environment.
AB  - This paper describes the framework of a real-time simulation system to model
      human behavior and reactions in dangerous environments. The system utilizes the
      latest 3D computer animation techniques, combined with artificial intelligence,
      robotics and psychology, to model human behavior, reactions and decision making
      under expected/unexpected dangers in real-time in virtual environments. The
      development of the system includes: classification on the conscious/subconscious
      behaviors and reactions of different people; capturing different motion postures
      by the Eagle Digital System; establishing 3D character animation models;
      establishing 3D models for the scene; planning the scenario and the contents; and
      programming within Virtools Dev. Programming within Virtools Dev is subdivided
      into modeling dangerous events, modeling character's perceptions, modeling
      character's decision making, modeling character's movements, modeling character's
      interaction with environment and setting up the virtual cameras. The real-time
      simulation of human reactions in hazardous environments is invaluable in military
      defense, fire escape, rescue operation planning, traffic safety studies, and
      safety planning in chemical factories, the design of buildings, airplanes, ships
      and trains. Currently, human motion modeling can be realized through established
      technology, whereas to integrate perception and intelligence into virtual human's
      motion is still a huge undertaking. The challenges here are the synchronization
      of motion and intelligence, the accurate modeling of human's vision, smell, touch
      and hearing, the diversity and effects of emotion and personality in decision
      making. There are three types of software platforms which could be employed to
      realize the motion and intelligence within one system, and their advantages and
      disadvantages are discussed.

PMID- 15850117
TI  - Incorporating 3D body motions into large-sized freeform surface conceptual
      design.
AB  - Large-sized free-form surface design presents some challenges in practice.
      Especially at the conceptual design stage, sculpting physical models is still
      essential for surface development, because CAD models are less intuitive for
      designers to design and modify them. These sculpted physical models can be then
      scanned and converted into CAD models. However, if the physical models are too
      big, designers may have problems in finding a suitable position to conduct their
      operations or simply the models are difficult to be scanned in. We investigated a
      novel surface modelling approach by utilising a 3D motion capture system. For
      designing a large-sized surface, a network of splines is initially set up.
      Artists or designers wearing motion marks on their hands can then change shapes
      of the splines with their hands. Literarily they can move their body freely to
      any positions to perform their tasks. They can also move their hands in 3D free
      space to detail surface characteristics by their gestures. All their design
      motions are recorded in the motion capturing system and transferred into 3D
      curves and surfaces correspondingly. This paper reports this novel surface design
      method associated with some case studies.

PMID- 15850118
TI  - User stress detection in human-computer interactions.
AB  - The emerging research area of Affective Computing seeks to advance the field of
      Human-Computer Interaction (HCI) by enabling computers to interact with users in
      ways appropriate to their affective states. Affect recognition, including the use
      of psychophysiologcal measures (e.g. heart rate), facial expressions, speech
      recognition etc. to derive an assessment of user affective state based on factors
      from the current task context, is an important foundation required for the
      development of Affective Computing. Our research focuses on the use of three
      physiological signals: Blood Volume Pulse (BVP), Galvanic Skin Response (GSR) and
      Pupil Diameter (PD), to automatically monitor the level of stress in computer
      users. This paper reports on the hardware and software instrumentation
      development and signal processing approach used to detect the stress level of a
      subject interacting with a computer, within the framework of a specific
      experimental task, which is called the 'Stroop Test'. For this experiment, a
      computer game was implemented and adapted to make the subject experience the
      Stroop Effect, evoked by the mismatch between the font color and the meaning of a
      certain word (name of a color) displayed, while his/her BVP, GSR and PD signals
      were continuously recorded. Several data processing techniques were applied to
      extract effective attributes of the stress level of the subjects throughout the
      experiment. Current results indicate that there exists interesting similarity
      among changes in those three signals and the shift in the emotional states when
      stress stimuli are applied to the interaction environment.

PMID- 15850119
TI  - Next generation autonomous wheelchair control.
AB  - Often times the physically challenged, limited to a wheelchair, also have
      difficulty with vision. In order to help, something must "see" for them.
      Therefore there must be some way for a wheelchair to know its environment, sense
      where it is, and where it must go. It also must be able to avoid any obstacles
      which are not normally part of the environment. An autonomous wheelchair will
      serve an important role by allowing users more freedom and independence. This
      design challenge is broken into four major steps: wheelchair control, environment
      recognition, route planning, and obstacle avoidance. The first step is to reverse
      engineer a wheelchair and rebuild the controls, which will be the main topic of
      discussion for this paper. Two big challenges with this step are high power motor
      control and joystick control. An H-bridge motor interface, controlled by a
      microprocessor, was designed for the motors. The joystick control is handled with
      the same microprocessor.

PMID- 15850120
TI  - A wearable, mobile phone-based respiration monitoring system for sleep apnea
      syndrome detection.
AB  - A new wearable respiration monitoring system has been developed for non-invasive
      detection of sleep apnea syndrome. The system, which is attached to a shirt,
      consists of a piezoelectric sensor, a low-power 8-bit single chip
      microcontroller, EEPROM and a 2.4 GHz low-power transmitting mobile phone (PHS).
      The piezoelectric sensor, whose electrical polarization voltage is produced by
      body movements, is installed inside the shirt and closely contacts the patient's
      chest. The low frequency components of body movements recorded by the sensor are
      mainly generated by respiration. The microcontroller sequentially stores the
      movement signal to the EEPROM for 5 minutes and detects, by time-frequency
      analysis, whether the patient has breathed during that time. When the patient is
      apneic for 10 sseconds, the microcontroller sends the recorded respiration
      waveform during and one minute before and after the apnea directly to the
      hospital server computer via the mobile phone. The server computer then creates
      apnea "filings" automatically for every patient. The system can be used at home
      and be self-applied by patients. Moreover, the system does not require any extra
      equipment such as a personal computer, PDA, or Internet connection.

PMID- 15850121
TI  - A motion control function evaluation system employing a pen tablet.
AB  - We have developed a new pen tablet based system for evaluation of hand motion
      control function as influenced by brain disease. The system consists of a laptop
      computer and a pen tablet data entry device. The pen tablet is placed in front of
      the subject who is instructed to tap the pen at a constant location. When the
      subject taps the pen, the tablet transfers the pen position to the laptop
      computer. The computer then saves the tap position, along with the time elapsed
      between each tap. The subject is instructed to tap 50 times with each hand with
      the eyes closed. The absolute distance moved between each two successive tap
      positions is detected. Tapping period, total tapping time and total distance
      moved are also calculated. Measurements were performed on ten normal subjects and
      three subjects with cerebral infarction. The results indicate that cerebral
      infarction subjects' average total tap point distance moved and absolute distance
      moved are greater than in the normal subjects. Conversely, all subjects in both
      groups produced only normal variations in tapping period and total tapping time.
      Our system can therefore quantitatively evaluate hand motion control function by
      the total and absolute distance moved.

PMID- 15850122
TI  - Infra-red radiant intensity exposure safety study for the Eye Tracker.
AB  - With any device that is used to record or evaluate biosignals, it is in the
      inventor's interest to determine how that device withstands a rigorous
      examination in regards to its inherent safety during use. For this, a Risk
      Management (Hazard) Analysis is a useful exercise. With this in mind, the most
      probable hazard concerning the Eye Tracker System (a device used to measure
      saccadic eye movements utilizing Reflective Differencing of Infra-Red light) is
      the exposure effect to the human eye caused by the Radiant Intensity of the IR
      emitters mounted on the Head Mounted Transducer. Presented in this article are
      the results of a study used to determine the Radiant Intensity exposure of the
      Eye Tracker as designed. Comparing these results with accepted norms for Radiant
      Intensity exposure, a redesign of the Head Mounted Transducer is detailed with
      results given showing that this new transducer fits safely into the accepted
      norms of Radiant Intensity exposure. Presented are the mathematical calculations
      used for the initial study and the redesign.

PMID- 15850123
TI  - Dynamic versus static analyses of lifting a box from the floor.
AB  - Lifting objects from below knee height has been implicated as a source of low
      back pain and injury. Static models have often been used to assess forces
      produced in the lumbar region by lifting; however, inertial forces generated by
      acceleration may be significant. Therefore, the goal of this investigation was to
      assess differences between static and dynamic analysis methods. Sagittal plane
      kinematics were collected on 21 men and 22 women of college age while lifting a
      milk crate (men = 25 kg, women = 15 kg) from the floor to standing knuckle height
      on level as well as sloped (facing uphill and downhill at 10 degrees and 20
      degrees) ground conditions. Both static and dynamic top-down inverse models were
      utilized to assess net muscular moments at L5/S1 as well as the posture of the
      person at the time of static max (TSM) and dynamic max (TDM) moments. The TDM
      moment was significantly later than the TSM in the level through uphill
      conditions (p < 0.001). The dynamic max moment was significantly greater than the
      static max moment in all conditions (p < 0.001). Torso angles at TSM exhibited a
      significantly greater forward lean (by < 2 degrees) in the level through uphill
      conditions (p < 0.001). Overall low-back curvature, hip angles, knee angles, and
      ankle angles were not affected by the type of model (p > 0.05), though several
      minor differences occurred at conditions other than the level (most dramatic in
      the downhill 20 degrees condition). Therefore, if moments are of interest, a
      dynamic model should be utilized. However, body position is very similar at TSM
      and TDM.

PMID- 15850124
TI  - Two assistive technology devices for children: an adjustable reacher and a lunch
      room chair.
AB  - Two devices were modified and redesigned to further improve on previous designs
      and to better suit the children they were originally constructed for. The first
      device is a reacher that needs to be adjustable. The child originally needed a
      reacher that was small enough to operate. Adult reachers were shortened to fit
      the child. It became apparent that the reachers would need to be able to grow
      with the child. For that reason a reacher was developed with interchangeable
      center sections and control rods. This allows the reacher to grow with child in
      increments without the need to keep sending the reacher in for modification. The
      reacher also needs to pinch on a different plane then it is controlled at to
      simplify use for the child. The second device modified was a chair built for
      children in wheel chairs to allow for them to sit with their peers at a lunch
      table at school. The chair was totally redesigned to be more comfortable and
      stronger. A removable cover was added so that it can be washed. A leg rest with
      adjustable foot rests was added so the children's feet are well supported and
      they are comfortable. This chair will allow the children to sit anywhere in the
      cafeteria so that they may sit with their peers.

PMID- 15850125
TI  - Bilateral asymmetries in max effort single-leg vertical jumps.
AB  - While asymmetries in the lower extremity during jumping may have implications
      during rehabilitation, it is not clear if healthy subjects should be expected to
      jump equivalently on each leg. Therefore, the goal of this study was to determine
      if asymmetries exist in maximal effort single-leg vertical jumps. After obtaining
      university-approved informed consent, 13 men and 12 women with competitive
      volleyball playing experience and no injuries of the lower-extremity that would
      predispose them to asymmetries participated. After thorough warm-up, five maximal
      effort vertical jumps with countermovement were performed on each leg (random
      order) with ground reaction forces and lower extremity kinematics recorded. The
      best three jumps from each leg were analyzed, assigning the leg with the highest
      jump height average as the dominant side. Asymmetry was assessed by determining
      statistical significance in the dominant versus non-dominant sides (p < 0.05). A
      significant interaction existed between side and gender for thigh length and peak
      vertical ground reaction force. Women had a significantly shorter thigh and men a
      greater peak vertical ground reaction force on their dominant side. All other
      parameters were assessed as whole group. Jumps were significantly greater off the
      dominant leg (2.8 cm on average). No other differences between sides were
      observed. Significant differences in magnitude (p < 0.05) existed between the men
      and women in jump height, several anthropometric parameters, minimum ankle and
      hip angles, and vertical ground reaction forces (peak and average). In
      conclusion, though a person may jump slightly higher on one leg relative to the
      other, and women may jump slightly differently than men, the magnitude of the
      difference should be relatively small and due to the multi-factorial nature of
      jump performance, individual parameters related to performance may not be
      consistently different.

PMID- 15850127
TI  - Classification of locomotor activity by acceleration measurement: validation in
      Parkinson disease.
AB  - The number of steps per time period is an important ambulatory measure describing
      an individual's locomotor function with implications for psychological and
      physical health. Key applications in neurology, psychiatry, psychopharmacology,
      and sports, behavior or rehabilitation medicine make it desirable to improve step
      detecting devices. Several pedometer or wrist actigraphy monitors exist today,
      but are insensitive or confounded by movement style, which may vary for different
      diagnoses and applications. Presented is an algorithm that detects, classifies
      and counts steps related to walking, running and shuffling motion. Data is
      recorded using a novel ambulatory monitoring system (LifeShirt, VivoMetrics,
      Inc., Ventura, CA, USA) which captures breathing information from respiratory
      inductive plethysmography (RIP) sensors embedded in a light garment, and
      acceleration signals from a dual axis accelerometer attached close to the center
      of body mass. The vertical accelerometer axis measures upward acceleration
      generated by walking and running, while the other axis measures movement common
      with shuffling gait. Since these signals often contain noise and artifact due to
      soft tissue movement or external vibrations they are filtered and autocorrelated
      using unbiased estimates. The autocorrelation coefficients allow for clearer
      detection and classification of the cyclic motion during walking, running and
      shuffling movements. The algorithm is tested during various levels of exercise in
      healthy individuals and patients suffering from Parkinson disease, which is often
      characterized by shuffling gait. The results demonstrate an effective locomotor
      monitoring algorithm that can produce accurate estimates of frequency and
      intensity of steps and shuffles and help classify daily locomotor activities.

PMID- 15850126
TI  - Gender comparison of knee strength recovery following ACL reconstruction with
      contralateral patellar tendon graft.
AB  - While gender appears to play a role in the incidence of Anterior Cruciate
      Ligament (ACL) injury, it is unclear if a gender bias in recovery following
      reconstruction exists. The goal of this investigation was to compare knee
      strength across gender from pre-operation through six months of rehabilitation
      following an acute rupture with no associated injuries compromising recovery. All
      operations were performed by the same surgeon (co-author: RVT) between 1996 and
      2002 using the middle 10 mm of the contralateral patellar tendon as the
      replacement graft. Of the 1,175 ACL patients seen by this surgeon, 102 (57 women
      and 45 men) fit the inclusion criterion which also required patients to have made
      every visit (pre-op, 5 wks, 10 wks, 4 months, and 6 months post-op) and completed
      every test (isokinetic knee flexion and extension at 180 degrees/s as well as
      isometric leg press). All patients were on the same rehabilitation program
      allowing for individualized advancement. Strength values were normalized to the
      uninvolved knee prior to surgery with a flexor/extensor ratio computed from
      isokinetic strength. There was a significant change (p < 0.05) in each parameter
      for both sides across time (p < = 0.003) except for the flexor/extensor strength
      ratio in the men on their involved side (p = 0.119). The only significant
      differences (p < 0.05) between gender at any time points were in the involved
      side flexor strength at 5 weeks (p = 0.029), 10 weeks (p = 0.013), and 4 months
      (p = 0.021) where the men were stronger. In conclusion, since recovery of
      strength following surgery is not identical between men and women, gender
      specific rehabilitation protocols may be warranted.

PMID- 15850128
TI  - Software model of a machine vision system based on the common house fly.
AB  - The vision system of the common house fly has many properties, such as
      hyperacuity and parallel structure, which would be advantageous in a machine
      vision system. A software model has been developed which is ultimately intended
      to be a tool to guide the design of an analog real time vision system. The model
      starts by laying out cartridges over an image. The cartridges are analogous to
      the ommatidium of the fly's eye and contain seven photoreceptors each with a
      Gaussian profile. The spacing between photoreceptors is variable providing for
      more or less detail as needed. The cartridges provide information on what type of
      features they see and neighboring cartridges share information to construct a
      feature map.

PMID- 15850129
TI  - Parametric evaluation of heart rate variability during the menstrual cycle in
      young women.
AB  - Evaluation of heart rate variability (HRV) is based on analysis of consecutive R
      R intervals and may provide quantitative information on the modulation of cardiac
      vagal and sympathetic efferent activities. In particular, power spectral analysis
      as well as the fractal dimension of HRV represent non-invasive measures that
      reflect brain-heart interaction in different physiopathological conditions. This
      study was performed to investigate the relationship between autonomic nervous
      cardiac influence and three phases (menses, follicular phase and luteal phase) of
      the menstrual cycle. Heart rate (HR) was recorded in 6 eumenorrheic young
      females, continuously for 20 min, at rest. From the tachograms, fractal
      dimension, FFT spectra and beta coefficient were evaluated. The components of two
      spectral bands were calculated: 0.040 Hz - 0.150 Hz (low frequency, LF), and
      0.150 Hz - 0.80 Hz (high frequency, HF). The results indicate no correlation
      between HR and follicular as well as luteal phase of the menstrual cycle. Total
      power and HF spectral component increase, whereas LF spectral component decreases
      in the luteal phase compared to the follicular one. The fractal dimension does
      not show significant differences among the three phases. Beta coefficient
      decreases during luteal phase in respect of follicular one and menses. In
      conclusion, these results indicate in healthy young women a correlation between
      female sex hormones (17 beta-oestradiol, progesterone and pituitary
      gonadotrophins) concentrations and some HRV parameters with higher HR variability
      during the luteal phase.

PMID- 15850130
TI  - Assessment of heart rate variability during alterations in stress: complex
      demodulation vs. spectral analysis.
AB  - Complex demodulation (CDM) has been proposed as a method for the analysis of high
      and low-frequency variabilities of heart rate and blood pressure under non
      stationary conditions. In contrast to power spectral analysis, CDM provides time
      dependent changes in signal amplitude and frequency on a continuous basis and may
      yield insights into short-term alterations in autonomic regulation. In
      particular, CDM may be uniquely suited for quantifying changes in respiratory
      sinus arrhythmia (RSA) at the onset of acute physical or mental stress
      conditions. In a simulation analysis we generated R-R interval time series within
      a normal physiological range that represented different typical sources of non
      stationarity present during varying stress. Sources of non-stationarity included
      abrupt changes in a) mean level (from 1000 to 500 ms within 60 sec), b)
      oscillatory amplitude (from 50 to 10 ms), c) oscillatory frequency (from 0.2 to
      0.4 Hz), and d) a combination of the above. In general, CDM-estimated amplitude
      and frequency accurately reproduced characteristics of the simulation data under
      all conditions, even after substantial noise and a 0.09 Hz oscillation were
      added. However, during some transitions CDM estimates fluctuated around the true
      values for up to 15 sec before they stabilized. Compared to CDM, power spectral
      analysis results were less informative since they did not allow the disentangling
      of unique contributions of distinct amplitudes and frequencies at different time
      points. Our analyses indicate that CDM provides a powerful means of continuously
      assessing time-dependent changes in RSA during varying physical or mental stress.
      CDM may also hold promise for a range of physiological and environmental non
      steady state conditions where rapid dynamic alterations in autonomic control are
      likely to occur.

PMID- 15850131
TI  - Safety enhancement of a specialized power assisted tricycle for a child with
      osteogenesis imperfecta type III.
AB  - A child in the community of Laramie, Wyoming was born with Osteogenesis
      Imperfecta which is a genetic disorder that limits the physical abilities, size,
      and strength of the child. A customized power assisted tricycle was developed,
      which offered a unique opportunity to serve multiple purposes in his childhood
      development. This tricycle will ultimately provide him with the opportunity to
      gain muscle mass, strength, coordination, and confidence. The tricycle was
      completed as a senior design project in 2002, funded by the National Science
      Foundation, Biomedical Engineering Program and research to Aid Persons with
      Disabilities Program and University of Wyoming, College of Engineering
      Undergraduate Design Project to Aid Wyoming Persons with Disabilities.
      Unfortunately, the tricycle did not provide the necessary features to allow him
      to ride the tricycle safely. For this reason the tricycle was redesigned to
      include many different redundant safety systems which allows the tricycle to be
      safe for the child's use. Being funded by the same grant, new systems were added
      to the tricycle. A panic kill switch, automatic brakes, numerous redundant
      velocity sensors, tip over prevention circuitry, a redesigned operating system, a
      battery recharge port, and other systems were added, allowing for the tricycle to
      provide a high level of safety. A great deal of testing and sound design
      practices have been taken into consideration throughout the addition of these
      systems. Without these improvements, the child would not have the opportunity to
      use the tricycle to help with his development.

PMID- 15850132
TI  - Modeling channel properties in vestibular calyx terminals.
AB  - Two types of hair cell have been described in the vestibular end organs of
      amniotes, but the coding of sensory signals by different hair cell types is not
      well understood. Type I hair cells are contacted by cup-shaped afferent calyx
      terminals, whereas type II hair cells are contacted by bouton terminals. The
      whole cell patch-clamp technique has been used to record voltage-dependent ionic
      currents from calyx terminals. Type I hair cells along with their calyces were
      non-enzymatically dissociated from the semicircular canals and utricles of
      Mongolian gerbils. Voltage-dependent currents identified in whole cell voltage
      clamp included transient inward sodium currents and outward potassium currents.
      Potassium currents were pharmacologically blocked by cesium in the patch
      electrode solution. The NEURON simulation environment was used to model the
      properties of the calyx terminal. A series of interconnected cylindrical
      compartments was designed to represent the inner and outer calyx membrane, the
      base of the calyx and a short axon segment. Kinetic parameters for the Na+
      current were optimized with a genetic algorithm to match kinetic data from the
      whole cell recordings.

PMID- 15850133
TI  - Design and implementation of an end tidal CO2 simulator for the evaluation of
      clinical gas analysers.
AB  - This paper presents a new technique to determine the dynamic and frequency
      response of capnographs using a custom built 'EtCO2 simulator system'.
      Capnographs are devices that use CO2 from a patients' expired breath to monitor
      the cardiopulmonary status during anaesthesia and mechanical ventilation.
      Capnographs at present are routinely calibrated via a static calibration method
      only. The dynamic response of the capnographs is not accounted for. The frequency
      and time response are important as they determine if capnographs can be used in
      high frequency and pediatric ventilation schemes. Experiments performed using the
      method described in this paper proved that old capnographs usually do not satisfy
      the manufacturer quoted specifications for time and frequency response.
      Therefore, a routine check for capnographs is recommended. The method can also be
      used to verify manufacturer quoted specifications. The EtCO2 simulator system,
      designed and constructed simulates human respiration cycle. The gas sources used
      are 5% CO2 and room air that can be switched alternatively. Both supplies are
      pressure regulated and connected through non-return valves to electric valves.
      The valves are microprocessor controlled and the on/off time is user defined
      allowing a wide range of waveforms to be simulated. The output from the simulator
      is delivered to capnograph. Capnograms are captured by digital video recording.
      The captured video in 'avi' file format is then converted into individual frames.
      These frames are converted into digital data through image processing in Matlab.
      The data obtained is subjected to extensive analysis to determine the frequency
      and time response of the respective capnograph.

PMID- 15850134
TI  - Teaching real-time ultrasonic imaging with a 4-channel sonar array, TI C6711 DSK
      and MATLAB.
AB  - Ultrasonic medical imaging courses often stop at the theory or MATLAB simulation
      level, since professors find it challenging to give the students the experience
      of designing a real-time ultrasonic system. Some of the practical problems of
      working with real-time data from the ultrasonic transducers can be avoided by
      working at lower frequencies (sonar to low ultrasound) range. To facilitate this,
      we have created a platform using the ease of MATLAB programming with the real
      time processing capability of the low-cost Texas Instruments C6711 DSP starter
      kit and a 4-channel sonar array. With this platform students can design a B-mode
      or Color-Mode sonar system in the MATLAB environment. This paper will demonstrate
      how the platform can be used in the classroom to demonstrate the real-time signal
      processing stages including beamforming, multi-rate sampling, demodulation,
      filtering, image processing, echo imaging, and Doppler frequency estimation.

PMID- 15850135
TI  - Comparison of the amelioration effects of two enzyme inducers on the inflammatory
      process of experimental allergic encephalitis (EAE) using immunohistochemical
      technique.
AB  - Experimental Allergic Encephalitis (EAE) is a T-cell mediated autoimmune disease,
      which resembles the human disease Multiple Sclerosis (MS) in rodents. The
      infiltration of inflammatory cells and the induction of astrocyte proliferation
      correlate with EAE severity. Oxidative stress is postulated to have a role in the
      onset and progression of MS. Therefore, by reducing oxidative stress via phase II
      enzymes inducers; namely the butylhydroxyanisole (BHA) and Thymoquinone
      (glutathione inducer), the inflammation could be ameliorated. EAE was induced in
      Lewis rats using Myelin Basic Protein (MBP) and complete Freund's adjuvant (CFA).
      Animals were placed into 1. those on normal rat chow, 2. those on rat chow
      containing BHA, 3. those receiving concomitant five day injection of thymoquinone
      days 1-5 post-EAE induction, 4. those receiving five doses of thymoquinone
      injected at day 12-17 post-EAE induction. Twenty-nine days later, animals from
      each group were sacrificed and tissues collected for immunohistochemistry using
      the anti-glial fibrillary acid (GFAP) antibody to examine the amelioration effect
      these two agents have on the inflammatory process occurring in EAE by examining
      the astrocyte proliferation in the Central Nervous System (CNS).

PMID- 15850136
TI  - The effect of conventional and sustained delivery of levodopa on SH-SY5Y
      neuroblastoma cells.
AB  - L-dihydroxyphenylalanine-(L-dopa) has been used for the treatment of Parkinson's
      disease for decades. Recently it has been shown that L-dopa, at concentrations of
      0.25 x 10(4) M or larger, can be toxic for human neuroblastoma cells. Toxicity
      has been associated with the productions of high levels of quinones. The reactive
      oxygen or nitrogen species generated in the enzymatical oxidation or auto
      oxidation of an excess amount of dopamine or L-dopa induce neuronal damage and/or
      apoptotic or non-apoptotic cell death. The objective of this study was to
      investigate if the delivery method could reduce the toxicity associated with
      higher levels of L-dopa. SH-SY5Y neuroblastoma cells were challenged with a bolus
      administration of 5, 50, 100 or 500 microM of L-dopa or a sustained delivery of L
      dopa to release the desired concentrations by the end of one incubation period.
      The cells were incubated for periods of 24, 48 or 72 hours, and at the end of
      each phase cell number, cell morphology, and cellular glutathione levels were
      determined. Conventional administration of L-dopa showed reductions in cell
      number at 72 hours in cells treated with 50 and 500 microM L-dopa. A similar
      trend was observed using drug delivery administration of L-dopa. Glutathione
      levels were reduced in the treatment groups after 24 hours and showed recovery by
      48 hours. Morphologic evaluation revealed that the lower dose groups appeared
      similar to control in both conventional and drug delivery whereas cellular
      distortion was observed at higher doses regardless of delivery method.
      CONCLUSION: Lower dose L-dopa was demonstrated to be less cytotoxic in SH-SY5Y
      neuroblastoma cells in both conventional and sustained drug delivery methods.

PMID- 15850138
TI  - Effects of mitomycin C on glaucoma filtration capsules.
AB  - One of the leading causes of implantable device failure is build up of scar
      tissue on the device. Approaches to address this complication range from choosing
      device materials that prevent cell adhesion to treatment with potent antifibrotic
      medications such as mitomycin C. We examined the collagen matrix around aqueous
      shunt implants in rabbit eyes and found the filtration capsule formed around
      these devices is not composed of scar tissue. Rather collagen deposition is
      highly organized with collagen bundles oriented along stress axes. We also
      examined adjacent tissue deposition in mitomycin C treated animals and found
      decreased vascularization, condensed collagen in Tenon's capsule with more
      collagen bundles less well formed than those in the control eye of the same
      animal. The sclera was thicker under the plate than at the opposite side of the
      same eye. Structural and functional evaluation correlates with the clinical
      paradox that patients treated with mitomycin C have lower initial pressures with
      adjunct drug treatment but lower success rates than the control population after
      18 months.

PMID- 15850137
TI  - Thymoquinone inhibits the activation of NF-kappaB in the brain and spinal cord of
      experimental autoimmune encephalomyelitis.
AB  - The present study was done to investigate the possible effects of thymoquinone on
      the inhibition of activation of NF-kappaB in experimental autoimmune
      encephalomyelitis in the rat model of multiple sclerosis. Experimental autoimmune
      encephalomyelitis was induced in Lewis rats by injecting myelin basic protein
      emulsified in complete freund's adjuvant. Several parameters including clinical
      signs, perivascular cuffing and infiltration of mononuclear cells in the brain
      and spinal cord, glutathione levels in the red blood cells and inhibition of the
      activation of NF-kappaB were determined to assess the degree of protection. The
      study showed that treatment of rats with thymoquinone 1 mg/kg/day concomitant to
      myelin basic protein and after the appearance of clinical signs resulted in
      preventing and ameliorating experimental autoimmune encephalomyelitis.
      Thymoquinone was able to counter perivascular cuffing and infiltration of
      mononuclear cells in the brain and spinal cord, increase the red blood cell
      glutathione, and inhibit the activation of NF-kappaB in the brain and spinal
      cord. These results were consistent with the clinical signs and suggest a
      beneficial effect of thymoquinone against experimental autoimmune
      encephalomyelitis in the rat model of multiple sclerosis.

PMID- 15850139
TI  - Systemic hypertension and nondiabetic chronic kidney disease: the best evidence
      based therapeutic approach today.
AB  - Despite the high prevalence and significant morbidity and mortality associated
      with high chronic kidney disease (CKD) in patients with hypertension, it remains
      vastly under-diagnosed and under-treated. Consequently, many patients develop
      kidney failure requiring dialysis or kidney transplant. Moreover, patients with
      CKD represent the group at highest risk from cardiovascular complications, even
      greater than patients with diabetes mellitus. Therefore, management of
      hypertension in such patients needs to be more aggressive compared to those with
      normal kidney function. This review provides guidelines for treatment of
      hypertension in patients with non-diabetic CKD based on updated evidence from
      clinical trials data. Following these recommendations is likely to minimize the
      risk of development of kidney failure and cardiovascular disease.

PMID- 15850140
TI  - Noninvasive assessment of coronary artery stenoses by multidetector-row spiral
      computed tomography: comparison with conventional angiography.
AB  - BACKGROUND: Coronary artery disease (CAD) is the most common cause of
      hospitalization and mortality in many industrialized countries. We analysed the
      diagnostic accuracy of multi-detector row spiral computed tomography (MDCT) in
      determining mid- to high-grade coronary artery stenoses (> 50%). METHODS: Sixty
      nine patients with suspected CAD were referred to MDCT coronary angiography.
      Patients with a heart rate above 60 bpm received 20-40 mg propranol before the
      scan. The left main (LM), the left anterior descending artery (LAD), the first
      diagonal branch (D1), the right coronary artery (RCA) and the proximal tract of
      the circumflex artery (LCX) were independently evaluated by two blinded observers
      and screened for > 50% stenoses. The mean values of MDCT coronary narrowings
      assessed by two observers were compared to quantitative coronary angiography.
      RESULTS: MDCT correctly detected 95 of 123 coronary lesions (sensitivity 77.2%)
      and absence of stenoses was correctly identified in 388 of 426 segments
      (specificity 91%). The sensitivity for the LM, LAD, RCA and the proximal tract of
      LCX was 100%, 86.5%, 69.8% and 80% respectively. Classification of patients as
      having 1-vessel, 2-vessels, 3-vessels or left main disease was accurate in 75.4%
      (46/61) of patients. CONCLUSIONS: MDCT technology, combined with heart rate
      control, allows reliable noninvasive detection of hemodynamically significant
      CAD.

PMID- 15850141
TI  - Epidemiology of passive smoke: a prospective study in 589 children.
AB  - BACKGROUND: Several studies have found that in children of smoking parents there
      is an increased incidence of respiratory illnesses and diminished pulmonary
      function. In infants of smoking atopic parents IgE levels are higher, atopic
      symptoms start earlier, and children are more likely to wheeze if the mother
      smokes than if she does not. Maternal smoking of 0.5 packs or more/day was
      identified as a risk for asthma developing in the 1st year of life. Among the
      environmental measures of our prevention program there is an absolute prohibition
      of smoking in the house of a "at risk" baby. MATERIALS AND METHODS: We have
      studied 289 atopic children, 169 males and 120 females, aged 3.5 to 7.5 years,
      attending our Division because affected by respiratory allergy. We have asked
      their parents if they smoked and if there were smoking relatives in their homes,
      independently of the number or the packs of cigarette smoked. The parents of 300
      children comparable for age and sex visiting our outpatient clinic for non
      respiratory disease served as controls. RESULTS: Smokers were 175 fathers and 109
      mothers of the asthmatic children and 153 fathers and 89 mothers of the controls.
      DISCUSSION: Analysis of data shows that passive smoking is significantly
      associated with the development of asthma in atopic children, and that males are
      more at risk than females. We stress that a high number of asthmatic children
      have atopic, and asthmatic parents. Cigarette smoke is not only a triggering
      factor of respiratory allergy in babies at risk of atopy, but especially an
      additional genetic factor, since asthma can be more easily provoked if an atopic
      parent smokes (more if both parents smoke), and even in children of not atopic,
      smoking parents.

PMID- 15850143
TI  - Polyunsaturated fatty acids and risk of preterm delivery.
AB  - Preterm delivery (PD) is characterized both by increased neonatal morbidity and
      mortality and by important late pathologic sequelae. From a clinical stand-point,
      PD may results from a medical condition where the continuation of pregnancy could
      bring about a marked risk for the foetus and/or for the mother, or from an
      adverse event where the pregnancy is going to end spontaneously before 37 weeks
      of gestation. In the past few years some epidemiological studies have shown that
      diet may interfere with complex multifactorial processes contributing to the
      preterm triggering of labour. The attention has been focused on polyunsaturated
      fatty acids (PUFA) such as alpha-linoleic acid, precursor of Omega-3 series, and
      linoleic acid, precursor Omega-6 series. Their importance in modulating
      Prostaglandin concentrations at different levels is already known. Moreover, it
      has been reported that in clinical situation, such as PD, the endogenous levels
      of PUFA are unbalanced, with a Omega-6 predominance. Experimental, observational
      and clinical studies suggest that dietary intake of Omega-3 fatty acids is
      capable of significantly prolonging the duration of gestation in the range of 4-7
      days; such prolongation would possibly occur through the inhibition of
      prostaglandins E2 and F2 alpha. In Western population dietary intake of Omega-3
      appears to be marginal, and recommended assumption could be reached only by a ten
      fold increase in blue fish ingestion. The recommended intake of EPA + DHA should
      be 1.4 g/daily with a 1:2.5 EPA:DHA. It is therefore possible to conclude that in
      light of controlled clinical studies and of the actual categories of risk for
      preterm delivery, the dietary supplementation of Omega-3, in addition to other
      pharmacological measures (17alpha-hydroxyprogesterone caproate), could be
      implemented for the secondary and/or tertiary prophylaxis of preterm delivery.

PMID- 15850142
TI  - Acute pancreatitis in the paediatric age group: a personal experience.
AB  - Although relatively rare, acute pancreatitis is the most common disease complex
      involving the pancreas in the paediatric age group. The etiology of the disease
      is often unknown, and Italian epidemiological data on the paediatric population
      and, in particular, on the etiology of the disease are not available (except for
      studies of prevalence). Within the field of the most frequently encountered
      pancreatitis in the age range of our interest (i.e. 0-18 years), not only the
      commonly observed forms whose etiopathogenesis is ascribable to cholelithiasis
      must be mentioned but also those forms due to proteic-caloric malnutrition that
      are becoming increasingly common. The presenting clinical symptoms and signs may
      not be typical and the laboratory tests may not always be sensitive enough. In
      such age range chronic recurrent pancreatitis plays a very important
      epidemiologic role. Approximately 40% of children and teenagers admitted to the
      hospital with a diagnosis of pancreatitis report a previous episode of the
      disease. Irreversible changes in pancreatic parenchyma develop in those patients
      in whom the disease progresses, leading to pancreatic insufficiency. Such a
      morbid condition (chronic pancreatitis) is more often observed in adolescents, in
      whom the disease manifests itself with a vague repetitive dyspeptic
      symptomatology, after alternating remissions and recrudescences, not always
      clinically evident. In children, the clinical picture most commonly encountered
      is represented by recurrent abdominal pains, in view of the fact that the
      patients are frequently affected by thalassaemia. The pseudocystic evolution of
      the disease is the most common organic damage resulting from the chronic
      progression of the pancreatic impairment. A few differences have been found with
      respect to severity, etiology, and mortality of pancreatitis in the paediatric
      age group as compared with older age groups. Both the general practitioner with a
      paediatric practice and the paediatrician encounter a large number of
      difficulties in this field of pathology. Therefore, an adequate and correct
      "management" of children with acute or chronic pancreatitis seems to be
      mandatory.

PMID- 15850144
TI  - Eight isolated cases of KBG syndrome: a new hypothesis of study.
AB  - We report on eight cases of patients affected by KBG syndrome (KBG stands for the
      initials of the affected patients in the original report), a rare genetic
      disease, that we find only in 40 cases mentioned in the scientific literature. In
      this work we present the minimum diagnostic criteria of diagnosis due to identify
      the syndrome and a hypothesis of study for the research of the involved factors.

PMID- 15850145
TI  - Diagnostic and surgical management of submandibular gland sialolithiasis: report
      of a stone of unusual size.
AB  - Sialolithiasis of the salivary glands is a relatively rare occurrence. It is the
      most common cause of acute and chronic infections. Sialoliths occurs in the
      submandibular gland in 80% of the cases and its etiology is associated with some
      anatomical factors proper of it. In many cases the diagnosis is easy due to
      obvious clinical features but, for treatment, imaging studies are always
      necessary. The most of the sialoliths are usually of 5 mm in maximum diameter and
      all the stones over 10 mm should be reported as a sialolith of unusual size. For
      these reason we considered useful to report our case in the managing of a stone
      13 mm placed in the submandibular gland context and its treatment by surgical
      resection of the entire gland.

PMID- 15850146
TI  - Management of thyrotoxic crisis.
AB  - The thyrotoxic crisis is a medical emergency caused by an exacerbation of the
      hyperthyroid state characterized by decompensation of one or more organ systems.
      Early recognition and aggressive treatment are fundamental in limiting the
      morbidity and mortality associated with this condition. The crisis has an abrupt
      onset, and is evoked by a precipitating factor such as infectious diseases,
      ketoacidosis, acute trauma, thyroidal surgery, 131-I radio-metabolic treatment,
      administration of iodine-containing materials (amiodarone), parturition. The
      clinical picture is characterized by four main features: fever, tachycardia or
      supraventricular arrhythmias, central nervous system symptoms and finally
      gastrointestinal symptoms. The diagnosis of thyrotoxic crises is often made on
      the basis of clinical findings alone, since it is difficult in most emergency
      departments to obtain rapid confirmatory laboratory or nuclear medicine tests.
      The ultrasound thyroid scan, if available in the emergency room, may suggest an
      hyperthyroid state showing typical images of Basedow's disease or nodular goiter
      with their characteristic color-Doppler pattern of hyperactivity, easily
      distinguishable from a normal gland. The principles of thyroid storm treatments
      are: reduction of circulating TH's levels; inhibition of the peripheral effects
      of circulating thyroid hormones (TH); supportive care, in order to reverse
      systemic decompensation and treatment of the underlying precipitating event.

PMID- 15850147
TI  - Let us acknowledge our baggage.

PMID- 15850148
TI  - A comparative study of professional competence of nurses who have completed
      different bridging programmes.
AB  - The aim of the study was to compare professional competence of nurses who
      completed different bridging programmes. Forty professional nurses from two
      different bridging programmes participated in the study. The newly qualified
      registered nurses were all from the province of Kwazulu- Natal working in various
      hospitals. The researcher utilized Slater Nursing Competencies Rating Scale. The
      instrument had the following categories (a) psychosocial (individual),
      psychosocial (group), (c) physical needs, (d) general, (e) communication and (f)
      professional implications. The results showed that newly qualified nurses from
      different bridging programmes were professionally competent. Age, experience and
      examination results had no relationship with the professional competency of the
      newly qualified nurse.

PMID- 15850149
TI  - Clinical teaching of student nurses by unit managers of selected hospitals in
      Limpopo Province.
AB  - The comprehensive nature of nurse training needs the involvement of almost all
      health team personnel, including unit managers to gain practical experience and
      learn to correlate theory and practice. The overall aim of the study was to
      explore and describe the experiences of unit managers regarding teaching of
      student nurses in the clinical area and to develop recommendations that will
      enhance clinical teaching, for the production of competent future nurse
      practitioners who will render quality care to patients. A qualitative design,
      which is explorative, descriptive and contextual in nature, was employed,
      utilizing a phenomenological approach to capture the experiences of unit managers
      regarding teaching of student nurses at selected hospitals, where students are
      allocated for their clinical exposure. Ethical measures as well as measures to
      ensure trustworthiness were adhered to. In-depth phenomenological interviews were
      conducted with unit managers who shared their experiences regarding clinical
      teaching of student nurses. Data analysis was done according to Tesch's (1990)
      open coding method. One major theme emerged, namely that unit managers
      experienced problems when doing clinical teaching of student nurses. Based on the
      findings the following recommendations were made: Colleges should open a two-way
      communication with unit managers, involvement of unit managers in the activities
      that take place at the college like courses, seminars and workshops on clinical
      teaching, learning contracts should be developed for the students and issues of
      clinical learning should be addressed and unit managers should be included in
      both summative and formative evaluations.

PMID- 15850150
TI  - An evaluation of the relevance and appropriateness of post-basic nursing
      programmes offered by the University of Zululand in meeting graduates'needs.
AB  - This article aims at evaluating the relevance and appropriateness of post-basic
      nursing programmes of the University of Zululand Nursing Science Department in
      meeting the educational needs of the graduates in the Province. An explanatory
      descriptive survey was conducted in the hospitals,clinics, nursing colleges,
      nursing schools and the University of Zululand where the nursing graduates
      worked. Two sets of interview schedules were designed, one for nursing graduates
      and one for their supervisors. These interview schedules consisted of open and
      closed-ended questions. The total number of graduates was 75 and 29 supervisors.
      The respondents were purposively and conveniently selected according to the
      availability of post-basic nursing graduates in each health and nursing education
      institution. The study revealed that post-basic nursing programmes of the
      University of Zululand catered for the changing learning needs of the graduates.
      This was due to the comprehensiveness of the programmes and their focus on
      community based and primary based health care from 1996. Based on the findings of
      the research it was recommended that a continuous evaluation of the post-basic
      nursing programmes is done, in order to check if they still meet the changing
      learning needs of the graduates. It was further recommended that the Nursing
      Science Department should develop more advanced clinical nursing programmes in
      order to cater for the recent learning needs of the graduates.

PMID- 15850151
TI  - Evaluation of HIV counselling and testing, self-disclosure, social support and
      sexual behaviour change among a rural sample of HIV reactive patients in South
      Africa.
AB  - The aim of this study was to evaluate HIV counselling and testing, self
      disclosure, social support and sexual behaviour change among HIV reactive
      patients among a rural sample of HIV reactive patients in South Africa. The
      sample consisted at the post-test counselling exit interview of 55 participants
      (41 women and 14 men) who tested HIV-positive conveniently selected from a rural
      hospital and at five months follow-up at their homes 47. Results indicated that
      most patients had an HIV test because of medical reasons. At follow-up only 36%
      had disclosed their HIV status and half of the participants had had sex without
      condoms in the past three weeks. Major reason for not disclosing of their HIV
      status were being afraid of negative reactions, fear of discrimination, fear of
      violence, concerns about confidentiality and not yet ready. Social support was
      found to be significantly related to disclosure of HIV status, while counselling
      context and content and counselling satisfaction were not related with HIV
      disclosure.

PMID- 15850152
TI  - Registered nurses' experience of the withdrawal of treatment from the critically
      ill patient in an intensive care unit.
AB  - In this article the results of research undertaken to explore and describe the
      experience of Registered Nurses regarding the withdrawal of treatment from the
      critically ill patient in an Intensive Care Unit (ICU), are discussed. Withdrawal
      of treatment from a critically ill patient in an Intensive Care Unit (ICU) is a
      very traumatic experience for all those involved. The Registered Nurse has the
      most contact with all those who are involved throughout the process. This raises
      questions regarding how the nurse experiences the withdrawal of treatment, and
      about guidelines that can be developed to accompany the nurse during the process
      of treatment withdrawal. The study was qualitative, descriptive, exploratory,
      descriptive and contextual in nature. Data was gathered by means of
      phenomenological interviews conducted by the researcher. Trustworthiness was
      ensured through the implementation of Guba's model (in Krefting 1991: 214). The
      following themes were identified: 1. The relationships the nurse develops with
      individuals involved in the process of treatment withdrawal. 2. The inner moral
      conflict experienced by the nurse relating to the ethical aspects of withdrawal
      of treatment. The focus of this article is on the discussion of these experiences
      of the registered nurses. Based on the identified themes, guidelines were
      developed to accompany the nurse during the process of withdrawal of treatment.

PMID- 15850153
TI  - The quality of integrated reproductive health services: perspectives of clients
      in KwaZulu-Natal, South Africa.
AB  - The focus of family planning programmes has shifted away from an emphasis on
      controlling fertility towards helping individuals achieve their reproductive
      goals. This article seeks to expand knowledge about the quality of integrated
      services from the perspective of clients at health facilities in KwaZulu-Natal.
      The results from 300 structured interviews with clients visiting health
      facilities found that overall quality of services was relatively high. However,
      the quality of services varied somewhat between rural and urban areas. Clients
      visiting urban health facilities reported greater satisfaction with services than
      clients visiting rural health facilities. The interviews with clients suggests
      that existing efforts to integrate services has had limited success. Clients were
      rarely offered an expanded range of services during their visit. In most cases,
      clients only received services for which they presented at the health facility.

PMID- 15850154
TI  - Experiences of primary health care nurses regarding the provision of free health
      care services in the northern region of the Limpopo Province.
AB  - The purpose of the study was to explore the experiences of primary health care
      nurses working in the clinics and health centres involved in the provision of
      free health care services. The research design followed was exploratory,
      descriptive and qualitative. The population of the study included all primary
      health care nurses working at the clinics and health centres in the Vhembe
      (northern) region of the Limpopo Province. The sampling method used was purposive
      for the samples of both the clinics and the nurses. The inclusion criteria for
      the nurses included experience of two or more years in providing primary health
      care. The inclusion criteria for the selection of clinics included being a busy
      clinic (a minimum of 2000 patients per month) with a staff establishment of four
      or more primary health care nurses. In conducting this research, ethical
      principles were taken into account. Data was collected from 23 participants in
      the Northern Region. The research question read as follows: What are your
      experiences regarding the provision of free health care services? An open coding
      method consisting of eight steps provided by Tesch's (1990:140-145) eight-step
      method of analysing data was used. The research findings revealed that the
      primary health care nurses working in the clinics experience feelings of failure
      to provide adequate primary health care services due to the increased workload,
      misuse of the service, and fear associated with lack of security in the clinics
      and health centres. The conclusions drawn from this research are that on the one
      hand a poor mechanism exists for the monitoring of the implementation of free
      health services, and on another hand, there has been misuse of the facilities by
      the community. The concept "free health care service" has been misinterpreted.

PMID- 15850155
TI  - Facilitating phenomenological interviewing by means of reflexology.
AB  - The aim of this article is to show how reflexology could facilitate
      phenomenological interviewing by probing the life-world of individual
      participants. It presents a hybrid study of phenomenological interviewing and
      reflexology as a holistic method of health care. In this sense, it is an
      interparadigmatic study, since it rests on the interface of Western and Oriental
      thought. This article reports on seven cases which were included in the
      qualitative, empirical investigation. During the sessions, reflexological
      readings served as impetus for inquiry into the experiences of the participants,
      as congestions on reflex points and along meridians were interpreted in terms of
      physical organs and functions. These readings were related to corresponding
      emotions as accepted within the reflexology paradigm. It was, however, up to the
      participants to inform the researcher of events and/or circumstances that caused
      the emotions. Thus, nonverbal data communicated information that facilitated
      verbal exchange concerning the life-world of each individual participant.

PMID- 15850156
TI  - Components of attentional set-switching.
AB  - A series of distinct event-related potentials (ERPs) have been recorded from the
      scalp of human subjects as they switch from one task to another. It is possible
      that task switching may depend on different mechanisms depending on whether the
      switch requires a change in attentional set, in other words the redirecting of
      attention to different aspects of a sensory stimulus, or whether it requires a
      change in intentional set, in others words a change in the way that responses are
      selected. To address this issue, the current study recorded ERPs while subjects
      switched between attentional sets and the results were compared with those of a
      previous investigation in which subjects switched between intentional sets.
      Subjects selected stimuli according to two conflicting attentional sets, each
      emphasizing one visual stimulus dimension (colour, shape). Pairs of stimuli, only
      one of which was to be attended, were presented for between eight and seventeen
      trials then either a switch or a stay cue was shown. The switch cue instructed
      subjects to switch from the current attentional set to the other set, while the
      stay cue instructed subjects to maintain the current set. Comparing ERPs time
      locked to the switch and stay cues revealed neural correlates of the initiation
      of a task switch. Comparing the ERPs time locked to the first stimuli after
      either stay or switch cues identified neural correlates of the implementation of
      a task switch. A similar modulation over parietal electrodes was seen when
      subjects were switching between either attentional or intentional sets. While an
      intentional set switch began with a medial frontal modulation, attentional set
      switching began with a lateral frontal modulation. Implementing a new attentional
      set was associated with modulation of relatively early visual potentials, while
      implementing a new intentional set was associated with modulation of later
      response-related potentials. The results confirm that task switching consists of
      a number of constituent processes which may be taxed to different degrees
      depending on whether a task-switch paradigm requires subjects to change the way
      in which they select stimuli or responses.

PMID- 15850157
TI  - The functional significance of theta and upper alpha oscillations.
AB  - Recent findings are reviewed indicating that upper alpha oscillations - when
      analyzed with appropriate time/ frequency resolution - show a similar
      physiological reactivity as theta in working memory tasks. Comparable to theta, a
      load dependent increase in power can be observed during retention and increased
      evoked activity during retrieval. During retrieval attempts theta behaves like a
      traveling wave spreading from anterior to posterior sites. During actual
      retrieval, however, evoked upper alpha becomes transiently nested in theta. We
      suggest that theta reflects working memory functions whereas upper alpha may be
      important for the reactivation of long-term memory codes in short-term memory.

PMID- 15850158
TI  - Phasic alertness and the residual task-switching cost.
AB  - Participants switched between two randomly ordered discrimination tasks and each
      trial began with the presentation of a task cue instructing which task to
      execute. The authors induced phasic alertness by presenting a salient
      uninformative stimulus after the task cue was provided, and at variable intervals
      before the target stimulus was presented (Experiments 1-3) or before the task cue
      (Experiment 4). When the alerting stimulus preceded the target stimulus or the
      task cue by an optimal interval, RT was faster, indicating an alert state and the
      task-switching cost was reduced. These results support the suggestion of De Jong
      (Acta Psychologica, 1999) that alertness improves the overcoming of retrieval
      competition through improved goal representation, but also show that the effect
      is specific to the residual task-switching cost.

PMID- 15850159
TI  - Inhibiting responses when switching: Does it matter?
AB  - In the present study, cued task-switching was combined with the stop-signal
      paradigm in order to investigate the interaction between response inhibition and
      task-switching. In line with earlier findings from Schuch and Koch (2003), the
      results show that switch and repetition trials following inhibited responses were
      processed equally fast. This confirms the hypothesis of Schuch and Koch (2003)
      that after signal-inhibit trials there is less interference, resulting in a
      disappearance of the switch cost. Furthermore, stopping performance was not
      affected by task-switching. The estimated stop-signal latencies were similar for
      switch and repetition trials, while the stop-signal delays were longer for switch
      compared to repetition trials. This result suggests that response inhibition and
      the inhibition processes in cued task-switching are not relying upon a common
      mechanism.

PMID- 15850160
TI  - Negative priming with masked distractor-only prime trials: awareness moderates
      negative priming.
AB  - The literature yields inconsistent evidence for negative priming (NP) following
      masked distractor-only prime trials. We contrast two different hypotheses on the
      inconsistent findings: one - which is most compatible with the temporal
      discrimination theory - that relates the sign of priming effects to the absence
      vs. presence of prime awareness and one -which is most compatible with the
      inhibition and episodic retrieval accounts - that relates the sign of priming
      effects to the prime event being categorized as a to-be-attended vs. to-be
      ignored event. In two experiments, it turned out that participants' awareness of
      the masked stimuli caused the different results (with participants being not
      aware of the primes showing NP), whereas the factor prime color = probe target
      color vs. prime color = probe distractor color (i.e., the prime contains the to
      be-attended vs. the to-be-ignored signal) did not moderate NP. These findings are
      discussed with regard to theories of negative priming and the debate on conscious
      vs. unconscious perception.

PMID- 15850161
TI  - Memory awareness following speeded compared with unspeeded picture recognition.
AB  - A remember-know paradigm was used to assess memory awareness following speeded
      and unspeeded yes/no picture recognition. The beneficial effects of picture size
      congruency at study and test occurred with speeded as well as with unspeeded
      recognition. In each case, they were associated with remembering, not with
      knowing, which remained invariant. Thus, size congruency effects were associated
      with remembering even when recognition occurred more automatically and hence may
      be more dependent on a relatively fast familiarity process. In a second
      experiment, speeded remember responses were compared with remember responses that
      followed speeded yes/no recognition. There was more remembering when it was the
      remember responses that were speeded, contrary to what might be expected if
      remembering reflects a relatively slow recollection process. These results have
      implications for the ability of dual-process models of recognition memory to
      account for memory awareness.

PMID- 15850162
TI  - Foveal vs. parafoveal attention-grabbing power of threat-related information.
AB  - We investigated whether threat words presented in attended (foveal) and in
      unattended (parafoveal) locations of the visual field are attention grabbing.
      Neutral (nonemotional) words were presented at fixation as probes in a lexical
      decision task. Each probe word was preceded by 2 simultaneous prime words (1
      foveal, 1 parafoveal), either threatening or neutral, for 150 ms. The stimulus
      onset asynchrony (SOA) between the primes and the probe was either 300 or 1,000
      ms. Results revealed slowed lexical decision times on the probe when primed by an
      unrelated foveal threat word at the short (300-ms) delay. In contrast, parafoveal
      threat words did not affect processing of the neutral probe at either delay.
      Nevertheless, both neutral and threat parafoveal words facilitated lexical
      decisions for identical probe words at 300-ms SOA. This suggests that threat
      words appearing outside the focus of attention do not draw or engage cognitive
      resources to such an extent as to produce interference in the processing of
      concurrent or subsequent neutral stimuli. An explanation of the lack of
      parafoveal interference is that semantic content is not extracted in the
      parafovea.

PMID- 15850163
TI  - [Neuropsychological assessment of ADHD subtypes].
AB  - Starting from a discussion of the validity of neuropsychological methods for the
      diagnosis of ADHD the results of an own study are presented. What is the
      diagnostic value of the German version of the CPT (Continuous Performance Task)
      and the DAT (Dortmunder Aufmerksamkeitstest) in discriminating ADHD subtypes
      (according to DSM-IV) and in which areas do the children of each subtype differ
      from a control group of normal children? The computer versions of the CPT and DAT
      were administered to 14 boys with the "combined subtype" of ADHD, 14 boys with
      the "predominantly inattentive type" of ADHD and 18 boys without clinical signs;
      all groups were matched in age and intelligence. Subsequently the mean
      differences between the various test parameters were assessed as to their
      significance. Contrary to other studies there were no significant differences
      either between both ADHS types or relative to the control group with regard to
      the CPT omission errors and the reaction time. There were differences in the
      reaction variability both between the ADHD subtypes and relative to the control
      group. Only the "combined subtype", not the "pre-dominantly inattentive type"
      differed from the control group as to the CPT commission errors. Regarding the
      DAT, there were significant differences between all three groups regarding both
      the solution quality and the response delay.

PMID- 15850164
TI  - [The psychopathy-concept and its psychometric evaluation in childhood and
      adolescence].
AB  - In accordance with Robert Hare's concept, over twenty years the word psychopathy
      is used to describe a specific combination of affective and interpersonal traits
      in adults as subtype of antisocial personality disorder. Recently in North
      America personality traits of psychopathy have also been studied in juveniles
      (and children). The Psychopathy Checklist: Youth Version (PCL-YV) was developed
      to take the special conditions of adolescents into account and focuses on
      assessing personality dimensions from age 12 upwards. In juveniles with a high
      score, research with the PCL-YV demonstrated for example a lack of empathy,
      impulsivity and social adjustment disorder. Furthermore, researchers found
      associations between the number and severity of violent offences, early drug
      abuse and heightened recidivism. This paper discusses the concept of psychopathy
      for adolescents on the basis of 3 case reports. Biological determinants,
      experimental results and diagnostic aspects are described.

PMID- 15850165
TI  - [Mental representation, psychic structure, and behaviour problems in preschool
      children].
AB  - Mental health problems in terms of deviant behaviour and emotional problems are
      assumed in context with mental representations and indicators of internal psychic
      structure. In distinction to adults there is little empirical research concerning
      this matter. On the basis of Childrens' Play Narratives (MacArthur Story Stem
      Battery) we collected data about content-themes, structural indicators and
      process criteria of 73 preschool children and implicated these information with
      behaviour ratings of parents and kindergarden teachers. Many correlations were
      found particularly with structural indicators, process criteria and behaviour
      ratings. The results are discussed both with respect to content and methodical
      aspects.

PMID- 15850167
TI  - DIPCON 2003. Proceedings of the 7th IWA International Specialised Conference on
      Diffuse Pollution and Basin Management, Dublin, Ireland, 17-21 August 2003.
AB  - This introduction gives a brief summary of the 7th International IWA Conference
      on Diffuse Pollution. The scope of the Conference topics is addressed and the
      main trends identified during its course are described.

PMID- 15850166
TI  - [Less severe sexual child abuse and its sequelae: are there different psychic and
      psychosomatic symptoms in relation to various forms of sexual interaction?].
AB  - A typology of less severe sexual encounters was used to analyze short and long
      term sequelae of sexual abuse via intimate skin contact. Well known theoretical
      approaches on the harmful effects of sexual abuse were tested. Do we find
      different peri- and posttraumatic reactions dependent upon varied forms of sexual
      interactions with children? A cluster analysis was calculated with symptom
      variables that were described in 141 child statements taken out of written expert
      opinions. Afterwards variance analyses of these symptom clusters were conducted
      in reference to six different abuse constellations. Different symptom profiles
      were found for these six abuse constellations. Panic symptoms, shame related
      feelings, avoidant behavior and physical reactions showed significant results.
      The sequelae to different forms of less severe sexual child abuse differ and
      depend more upon the situational dynamic than upon the kind of relationship
      between adult and child.

PMID- 15850168
TI  - The next step--incorporating diffuse pollution abatement into watershed
      management.
AB  - The majority of adverse changes in watersheds impairing water quality occurred
      over a period of thirty to more than one hundred years. In many areas over a
      period of about 80 years more than 90% of the wetlands were drained, cultivated
      and converted to agricultural and urban uses. This conversion changed the redox
      status of the soils and soil cover with a concurrent large increase of suspended
      solids, dissolved organic matter, nitrogen, and phosphate loads from the
      watersheds located in the affected regions. The question whether these adverse
      changes are reversible by reduction or discontinuation of excessive inputs of
      pollutants came to light and has been analyzed recently after the political
      changes in Eastern Europe. Reliable dynamic long term models that would describe
      interactions between nutrient inputs, outputs, storage etc., have not been
      developed yet. It is becoming apparent that it may take longer for the watersheds
      to recover after nutrient loads to surface and groundwater are reduced if
      remedial measures are gradually implemented.

PMID- 15850169
TI  - Simulation supported scenario analysis for water resources planning: a case study
      in northern Italy.
AB  - The work presents the results of a comprehensive modelling study of surface and
      groundwater resources in the Muzza-Bassa Lodigiana irrigation district, in
      Northern Italy. It assesses the impact of changes in land use and irrigation
      water availability on the distribution of crop water consumption in space and
      time, as well as on the groundwater resources. A distributed, integrated surface
      water-groundwater simulation system was implemented and applied to the study
      area. The system is based on the coupling of a conceptual vadose zone model with
      the groundwater model MODFLOW. To assess the impact of land use and irrigation
      water availability on water deficit for crops as well as on groundwater system in
      the area, a number of management scenarios were identified and compared with a
      base scenario, reflecting the present conditions. Changes in land use may alter
      significantly both total crop water requirement and aquifer recharge. Water
      supply is sufficient to meet demand under present conditions and, from the crop
      water use viewpoint, a reduction of water availability has a positive effect on
      the overall irrigation system efficiency; however, evapotranspiration deficit
      increases, concentrated in July and August, when it may be critical for maize
      crops.

PMID- 15850170
TI  - Nitrogen retention in a river system and the effects of river morphology and
      lakes.
AB  - The mean annual transfer (loss and retention) of nitrogen in a river system was
      estimated using a conceptual approach based on water surface area and runoff. Two
      different approaches for the calculation of water surface area were applied to
      determine riverine nitrogen retention in four European catchments, ranging
      between 860-14,000 km2 in area, and differing considerably in the proportion and
      distribution of surface waters, specific runoff and specific nutrient emissions.
      The transfer rate was estimated sequentially as either the mean value for the
      total catchment, on a sub-catchment scale, or considering the distribution of
      water surface area within a sub-catchment. For the latter measure, nitrogen
      retention in larger lakes was calculated separately. Nitrogen emissions modelled
      with MONERIS and HBV-N were used to calculate nitrogen river loads and compare
      those with observed loads. Inclusion of the proportion of water area within a sub
      catchment improved modelled results in catchment with large lakes in sub
      catchments, but not where there was a homogenous distribution of surface waters
      among sub-catchments.

PMID- 15850171
TI  - Nutrient transport scenarios in a changing Stockholm and Malaren valley region,
      Sweden.
AB  - Norrstrom catchment, west of Stockholm, covers most of the Malaren valley.
      Provision of drinking water from Lake Malaren is an absolute precondition for
      continued growth in the region. Stockholm County's population is expected to
      increase by 600,000 people before 2030. Current climate change predictions
      anticipate significant temperature and precipitation increases. We implement the
      PolFlow model embedded in PCRaster for quantifying water and substances fluxes on
      the catchment scale over a 30-year time horizon. We formulate scenarios for
      changes in water quality and quantity due to climate change and population
      development. Results indicate a mild impact from climate change on surface flow
      rates but substantial effects on sub-surface residence times. Population
      development slightly affects nutrients loads. Using source apportionment and
      sensitivity analysis, we identify a number of critical parameters/processes to be
      further studied, in order for future results to be more reliable and usable in a
      water resources management context.

PMID- 15850172
TI  - Assessment of the spatial heterogeneity of weathering rates in upland catchments
      using the sodium dominance index and its significance in integrated catchment
      management.
AB  - The sodium dominance index was developed to quantify weathering rates and
      critical loads in Scotland, where atmospheric aerosols of maritime origin
      dominate over biogeochemical weathering in providing base cation inputs to
      catchment soils and drainage waters. High sodium dominance in river or lake water
      indicates low weathering rate. Here, this concept is evaluated using intensive
      temporal and spatial sampling strategies in two substantial catchments, one in
      Scotland and the other in central England, with particular reference to detection
      of groundwater inputs, and to possible problems from road salting in the
      calibration. In the Dee network, the spatial distribution of sodium dominance
      reflects the distribution of soil parent material geology, but land use also
      influences the equations. It is postulated that road density, via winter road
      salting, influences the sodium dominance calibration in lowland agricultural
      areas. Although road salting can also be problematic in some upland areas, the
      index still can provide clear indication of the likely severity of acid flush
      events in remote upland streams. In the Etherow catchment, sodium dominance
      varies markedly, sometimes over relatively small distances, reflecting soil type
      distribution, the occurrence of ground-water inputs to streams, and the influence
      of water in tributaries above the sampling point.

PMID- 15850173
TI  - Including non-point sfources in a water quality trading permit program.
AB  - There has been overwhelming interest in addressing water quality issues through
      the use of economic instruments. Much of this attention has focused on the cost
      efficiencies offered by Transferable Discharge Permit (TDP) systems.
      Unfortunately, the attempts to start up permit markets which are able to exploit
      abatement cost differences between sources have not met with the success
      expected. Two of the reasons for the lack of success that have been taken up in
      analysis of these programs have been the problem of transaction costs and in the
      case of non-point sources (NPS), undefined property rights. The composite market
      design is a proposal for a TDP system which specifically includes agricultural
      non-point source (NPS) dischargers and addresses both property rights and
      transaction cost problems. The composite market consists of three interrelated
      markets each serving a particular function. When the composite market is mature,
      the total number of permits issued represents the cap on discharges allowed in
      the catchment. The structure of the composite market allows this system to be
      phased in over time with existing institutions and limited demands on financing.

PMID- 15850174
TI  - Buffer zones as a sink for sediment and phosphorus between the field and stream:
      Danish field experiences.
AB  - Rill erosion, surface runoff and storage of sediment and phosphorus in buffer
      zones were investigated during three winters on ca. 140 arable field slope units
      in twenty places in Denmark covering all landscape types, climate gradients and
      dominant soil types. The dominant soils are Alfisols and Spodosols, with textural
      composition typically ranging from sand to loam. The average slope is 7% (range:
      2-20%) and median buffer zone width was 8.3 m (range: 0.6-125 m). The geometric
      mean annual rill erosion was 0.33 m3 ha(-1) equalling to 495 kg sediment ha(-1)
      and 0.25 kg P ha(-1). The deposition of sediment on the field, in the buffer zone
      and delivery of soil to the stream was surveyed within the 140 slope units
      following three winters. Deposition of sediment in the buffer zone was observed
      in 31% (1997/98), 31% (1998/99) and 29% (1999/2000) of the slope units. Delivery
      of soil across the edge of the stream was observed in 23% (1997/98), 17%
      (1998/99) and 25% (1999/2000) of the 140 slope units. Median dissolved P
      concentration in surface runoff was 0.18 mg Pl(-1) (range: 0.029-16.294 mg Pl(
      1)). A probability model was developed to predict the efficiency of different
      widths of buffer zones.

PMID- 15850175
TI  - Cold-climate vegetative buffer zones as pesticide-filters for surface runoff.
AB  - Vegetative buffer zones adjacent to watercourses can be effective filters for
      diffuse pollution from agriculture. Several investigations, even during snowmelt
      season, have shown that retention of sediments and sediment-bound nutrients in
      runoff water has been high through buffer zones (BZ). It is likely that BZ also
      can be effective filters for sediment-bound pesticides. The retention of
      glyphosate, propiconazole, fenpropimorph and soil particles was studied in
      surface runoff experiments with 5 m wide buffer zones. Volume proportional
      samples were collected after each runoff episode (1999-2002). The distribution
      coefficient (Kd) shows moderate to high adsorption of the pesticides to the
      experimental soil. Results show average retention efficiency of about 51%, 48%,
      85% and 34% for particles, glyphosate, propiconazole and fenpropimorph,
      respectively. The amount of AMPA (which is a degradation product of glyphosate),
      entering the BZ was high; approximately the same amount as for glyphosate. The
      retention efficiency through the BZ for AMPA was about 67%. There were no
      significant differences in removal efficiency (in %) between winter with snowmelt
      and summer. This is possibly due to detachment of coarser aggregates during
      winter, which trap more easily in the BZ. The conclusion based on this study
      suggests BZ to be contributors to reduced pesticide input to surface waters.

PMID- 15850176
TI  - The impact of agricultural management practices on nutrient losses to water: data
      on the effects of soil drainage characteristics.
AB  - Against the background of increasing nutrient concentrations in Irish water
      bodies, this study set out to gain information on the potential of agricultural
      grassland to lose nutrients to water. Overland flow, flow from artificial
      subsurface drains and stream flow were gauged and sampled during heavy rainfall
      events. Dissolved reactive phosphorus (DRP), potassium (K), total ammonia (TA),
      and total oxidised nitrogen (TON) were measured in water samples. When the
      nutrient concentrations in water were examined in relation to the grassland
      management practices of the study catchments it emerged that soil P levels, the
      application of organic and inorganic fertilisers before heavy rainfall and the
      presence of grazing animals could all influence nutrient concentrations in
      surface and subsurface drainage water. Overall, the drainage characteristics of
      soil were found to have a considerable influence on the potential of land to lose
      nutrients to water.

PMID- 15850177
TI  - A statistical approach to estimate nitrogen sectorial contribution to total load.
AB  - This study describes a source apportionment methodology for nitrogen river
      transport. A statistical model has been developed to determine the contribution
      of each source (punctual and diffuse) of nitrogen to river-mouth transport. A non
      linear regression equation was developed, relating measured nitrogen transport
      rates in streams to spatially referenced nitrogen sources and basin
      characteristics. The model considers applied fertilizer, atmospheric deposition
      and point discharges as sources, and winter rainfall, average air temperature,
      topographic wetness index and dry season flow as basin characteristics. The model
      was calibrated in an area of 8913 km2 in East Anglia (UK). In the studied area,
      the average contribution of agriculture to the nitrogen load is estimated around
      71%. Point sources and atmospheric deposition respectively account for 24% and 5%
      of the exported nitrogen. The model allowed the estimation of the contribution of
      each source to nitrogen emissions and the nitrogen retention in soils and waters
      as influenced by basin factors.

PMID- 15850178
TI  - Model analysis for nitrogen effluent from upland field constructed with under
      drain.
AB  - A mathematical model to estimate nitrogen (N) effluent from an upland field
      cultivated with barley, where under-drain pipes were installed 60 cm below the
      field surface, was developed and N effluents for several rainfall patterns during
      the cultivation period were analysed. The model is composed of the water drainage
      model and N cycle model. The water drainage model is made up of Sugawara's tank
      model in which the field is divided into two soil types, permeable soil and
      impermeable soil, and macro pore. The N cycle model can calculate the N reactions
      including nitrification, denitrification, mineralization, immobilization, urea
      hydrolysis and N transportation in the field. By using this model, N effluents
      caused by rainfall were analysed and characteristics of N effluent were
      clarified. The under drainages caused by heavy rains which occur around 60 days
      after fertilization contribute greatly to the amount of N effluent load during a
      cultivation period. Also, split application of fertilizer is not effective for
      the reduction of N effluents under any cultivation conditions, especially in
      winter crops. A large quantity of N effuses out of the field because the major
      portion of rainfall in a cultivation period occurs in the latter half of the
      period.

PMID- 15850179
TI  - Mass balance analysis and water quality model development for loading estimates
      from paddy fields.
AB  - Mass balance analysis and water quality model development for paddy field were
      performed using field experimental data during 2001-2002. About half (47-62%) of
      the total outflow was lost by surface drainage, with the remainder (490-530 mm)
      occurring by evapotranspiration. Most of nutrient inflow and outflow were
      mediated by fertilization and plant uptake, respectively. Nutrient outflow by
      surface drainage runoff was substantial about 15%-29% for T-N and 6%-13% for T-P.
      However, the responses of yield and drainage outflow to fertilization were not
      significant in this study. A water quality model applicable to paddy fields was
      developed and it demonstrates good agreement with observed data. The nutrient
      concentration of ponded water was high by fertilization at early culture periods,
      so reducing surface drainage during fertilization period can reduce nutrient
      loading from paddy fields. Shallow irrigation, raising the weir height in diked
      rice fields, and minimizing forced surface drainage are suggested to reduce
      surface drainage outflow.

PMID- 15850180
TI  - Synthetic- and bio-polymer use for runoff water quality management in irrigated
      agriculture.
AB  - Low concentrations of synthetic- or bio-polymers in irrigation water can nearly
      eliminate sediment, N, ortho- and total-P, DOM, pesticides, micro-organisms, and
      weed seed from runoff. These environmentally safe polymers are employed in
      various sensitive uses including food processing, animal feeds, and potable water
      purification. The most common synthetic polymer is anionic, high purity
      polyacrylamide (PAM), which typically provides 70-90% contaminant elimination.
      Excellent results are achieved adding only 10 ppm PAM to irrigation water,
      applying 1-2 kg ha(-1) per irrigation, costing 4 dollars - 12 dollars kg(-1).
      Biopolymers are less effective. Using twice or higher concentrations, existing
      biopolymers are approximately 60% effective as PAM, at 2-3 times the cost. A half
      million ha of US irrigated land use PAM for erosion control and runoff
      protection. The practice is spreading rapidly in the US and worldwide. Interest
      in development of biopolymer surrogates for PAM is high. If the supply of cheap
      natural gas (raw material for PAM synthesis) diminishes, industries may seek
      alternative polymers. Also "green" perceptions and preferences favor biopolymers
      for certain applications.

PMID- 15850181
TI  - Assessment of environmental impacts following alternative agricultural policy
      scenarios.
AB  - Abstract Finnish agriculture is likely to undergo major changes in the near and
      intermediate future. The ifuture policy context can be examined at a general
      level by strategic scenario building. Computer-based modelling in combination
      with agricultural policy scenarios can in turn create a basis for the assessments
      of changes in environmental quality following possible changes in Finnish
      agriculture. The analysis of economic consequences is based on the DREMFIA model,
      which is applied to study effects of various agricultural policies on land use,
      animal production, and farmers' income. The model is suitable for an impact
      analysis covering an extended time span--here up to the year 2015. The changes in
      land use, obtained with the DREMFIA model assuming rational economic behaviour,
      form the basis when evaluating environmental impacts of different agricultural
      policies. The environmental impact assessment is performed using the field scale
      nutrient transport model ICECREAM. The modelled variables are nitrogen and
      phosphorus losses in surface runoff and percolation. In this paper the modelling
      strategy will be presented and highlighted using two case study catchments with
      varying environmental conditions and land use as an example. In addition, the
      paper identifies issues arising when connecting policy scenarios with impact
      modelling.

PMID- 15850182
TI  - The effect of the redox-potential on the retention of phosphorus in a small
      constructed wetland.
AB  - Building wetlands in small arable streams is a popular supplement to best
      management practice on arable fields. Particle bound phosphorus settles in the
      small constructed wetlands (CWs), receiving agricultural diffuse pollution. The
      sorption behavior of phosphorus is, however, redox-sensitive, and bound
      phosphorus may be remobilized in periods with low redox potential. This paper
      investigates changes in the redox potential in the free water of wetland Berg
      (Norway) during a three-year period, and how these redox changes affect the total
      phosphorus (TP) and total reactive phosphorus (TRP) retention. Despite eutrophic
      conditions in the wetland, the redox potential was never negative, and usually
      higher than 400 mV, indicating aerobic conditions. The relative retention was
      440% and 43% for TP and TRP, respectively. The specific retention was 100 g TP
      and 43 g TRPm(-2) yr(-1). Loss of phosphorus was only observed during less than
      19% of the total period of time. The net loss was less than 5% of the specific
      retention. The high positive redox potential probably conserves the redox
      sensitive phosphorus in the wetland sediment as long as water fows through the
      CW.

PMID- 15850183
TI  - Developing an independent, generic, phosphorus modelling component for use with
      grid-oriented, physically based distributed catchment models.
AB  - Grid-oriented, physically based catchment models calculate fields of various
      hydrological variables relevant to phosphorus detachment and transport. These
      include (i) for surface transport: overland flow depth and flow in the coordinate
      directions, sediment load, and sediment concentration and (ii) for subsurface
      transport: soil moisture and hydraulic head at various depths in the soil. These
      variables can be considered as decoupled from any chemical phosphorus model since
      phosphorus concentrations, either as dissolved or particulate, do not influence
      the model calculations of the hydrological fields. Thus the phosphorus
      concentration calculations can be carried out independently from and after the
      hydrological calculations. This makes it possible to produce a separate
      phosphorus modelling component which takes as input the hydrological fields
      produced by the catchment model and which calculates, at each simulation time
      step, the phosphorus concentrations in the flows. This paper summarises the
      equations and structure of such a Grid Oriented Phosphorus Component (GOPC)
      developed by the authors for simulating phosphorus concentrations and loads using
      the outputs of a fully distributed physical based hydrological model. The GOPC
      performance is illustrated by an example of a simplified hypothetical catchment
      subjected to some ideal conditions.

PMID- 15850184
TI  - Pesticide retention in the watershed and in a small constructed wetland treating
      diffuse pollution.
AB  - Loss of pesticides is likely from watersheds where pesticides are used. The
      herbicides propachlor, linuron and metamitron, and the fungicides propiconazole,
      fenpropimorph and metribuzin and metalaxyl, were applied on an arable soil plot.
      A mass balance study showed that approximately 96% of the applied pesticides
      disappeared within the watershed. Three pesticides remained as residuals in the
      soil profile one year after the application. The 4% of the pesticides that were
      lost from the watershed gave peak concentrations, appearing immediately after
      spraying, reaching levels that can be hazardous to aquatic life. The constructed
      wetland situated in the first-order stream generally managed to lower the peak
      concentrations significantly. For the summer season, retention varied from 12 to
      67% the first year. The second year, we observed both loss and retention.
      Increasing the wetland surface from 0.2% to 0.4% of the watershed area increased
      the average retention with 21% units the first year and 9% units the second year.
      Chemical properties of the pesticides could explain some of the behaviour in the
      watershed and in the wetland.

PMID- 15850185
TI  - Nutrient balance in a paddy field with a recycling irrigation system.
AB  - We studied nutrient balance in a paddy field that had a recycling irrigation
      system and evaluated the effect of the irrigation system on nutrient balance
      during the irrigation period, from April to August 2002. Chemical fertilizer was
      the main input of phosphorus; the soil absorbed about 56% of it. The amount of
      nitrogen supplied by the irrigation system was higher than in a representative
      paddy field, and the amount of nitrogen fertilizer used was decreased because the
      irrigation water was partly reused. About 20% of applied nitrogen was lost by
      denitrification. The net outflows of phosphorus and nitrogen were -0.37 and -3.98
      kg ha(-1), respectively. These results indicate that our study paddy field
      performed well in removing phosphorus and nitrogen compounds from runoff water. A
      recycling irrigation system can be considered an effective way of reducing the
      amounts of water and fertilizer used and reducing the outflow nutrients.

PMID- 15850186
TI  - A new modeling approach for estimating first flush metal mass loading.
AB  - The purpose of this study was to investigate pollutant mass loading from major
      highways in Southern California, with emphasis on interpretation of event mean
      concentrations and first flush effects. The results of monitoring eight sites
      during the 1999-2002 storm seasons found that metal contaminants had higher
      concentrations at the early stages of storm events compared with other stages of
      rain storms. A new washoff model was developed to predict the event mean
      concentrations of metal contaminants taking first flush effect into account.
      Model variable parameters included average daily traffic, antecedent dry period,
      rain intensity, total runoff volume, and runoff coefficient. The results obtained
      using the washoff model were compared with measured values and found to fit well
      for heavy metals with R2 ranging from 0.8 to 0.95.

PMID- 15850188
TI  - Multiple-event study of bioretention for treatment of urban storm water runoff.
AB  - Bioretention is a novel best management practice for urban storm water, employed
      to minimize the impact of urban runoff during storm events. Bioretention consists
      of porous media layers that can remove pollutants from infiltrating runoff via
      mechanisms that include adsorption, precipitation, and filtration. However, the
      effectiveness of bioretention in treating repetitive inputs of runoff has not
      been investigated. In this study, a bioretention test column was set up and
      experiments proceeded once every week for a total of 12 tests. Through all 12
      repetitions, the infiltration rate remained constant (0.35 cm/min). All 12 tests
      demonstrated excellent removal efficiency for TSS, oil/grease, and lead (99%).
      For total phosphorus, the removal efficiency was about 47% the system removal
      efficiency ranged from 2.3% to 23%. Effluent nitrate concentration became higher
      than the influent concentration during the first 28 days and removal efficiency
      ranged from 9% to 20% afterward. Some degree of denitrification was apparently
      proceeding in the bioretention system. Overall, the top mulch layer filtered most
      of TSS in the runoff and prevented the bioretention media from clogging during 12
      repetitions. Runoff quality was improved by the bioretention column.

PMID- 15850187
TI  - Estimation of origins of polycyclic aromatic hydrocarbons in size-fractionated
      road dust in Tokyo with multivariate analysis.
AB  - This study aimed to estimate the origins of polycyclic aromatic hydrocarbons
      (PAHs) in size-fractionated road dust in Tokyo. First, seven categories of PAHs
      sources were defined: diesel vehicle exhaust, gasoline vehicle exhaust, tire,
      pavement, asphalt or bitumen, petroleum products excluding tire and asphalt, and
      combustion products except for those in vehicle engines. The 189 source data of
      12-PAHs profiles were classified into 11 groups based on cluster analysis
      combined with principal component analysis. Next, 18 road dust samples were
      collected from eight streets in Tokyo and fractionated into four different
      particle-size-fractions: 0.1-45, 45-106, 106-250, and 250-2000 microm. In order
      to estimate the contributions of the classified source groups (S1-S11) to PAHs in
      the road dust, multiple regression analysis was performed with 12-PAH profile of
      the road dust as dependent variable and average 12-PAHs profiles of the 11 source
      groups as 11 explanatory variables. Diesel vehicle exhaust, tire and pavement
      were the major contributors of PAHs in the fractionated road dust. Although the
      estimated contributions of the 11 source groups varied among the particle-size
      fractions, there was no clear and consistent relationship between particle size
      and the major PAH contributor.

PMID- 15850189
TI  - Urban diffuse sources of faecal indicators.
AB  - Increasing concern about bathing water quality in Scotland has led to renewed
      interest in diffuse sources, as well as the already closely monitored municipal
      sewage effluents and combined sewer overflows (CSOs) that have been the subject
      of multi-million pound capital expenditure schemes for several years. Early
      investigations of diffuse sources focused on rural land uses. This paper is an
      initial effort to consider the possible significance of urban diffuse sources. A
      review of the potential for diffuse urban sources includes consideration of
      sewage pollution in surface water sewers, as well as non-human sources such as
      pigeon and other bird roosts, and faecal material from pets such as dogs and
      cats. Portobello beach in Edinburgh is the case study selected, because of
      earlier work done by Scottish Water and SEPA. The Figgate Burn crosses Edinburgh
      to discharge onto the beach at Portabello, and pollution sources in its catchment
      are described. Additional information is reported from Dunfermline, where the
      sewer network has provided examples of three ways in which sewage pollution can
      occur in urban streams, and also Scottish examples of measures to control some
      non-human sources (e.g. SUDS).

PMID- 15850190
TI  - Estimation of diffuse and point source microbial pollution in the ribble
      catchment discharging to bathing waters in the north west of England.
AB  - Achieving compliance with the mandatory standards of the 1976 Bathing Water
      Directive (76/160/EEC) is required at all U.K. identified bathing waters. In
      recent years, the Fylde coast has been an area of significant investments in
      'point source' control, which have not proven, in isolation, to satisfactorily
      achieve compliance with the mandatory, let alone the guide, levels of water
      quality in the Directive. The potential impact of riverine sources of pollution
      was first confirmed after a study in 1997. The completion of sewerage system
      enhancements offered the potential for the study of faecal indicator delivery
      from upstream sources comprising both point sources and diffuse agricultural
      sources. A research project to define these elements commenced in 2001.
      Initially, a desk study reported here, estimated the principal infrastructure
      contributions within the Ribble catchment. A second phase of this investigation
      has involved acquisition of empirical water quality and hydrological data from
      the catchment during the 2002 bathing season. These data have been used further
      to calibrate the 'budgets' and 'delivery' modelling and these data are still
      being analysed. This paper reports the initial desk study approach to faecal
      indicator budget estimation using available data from the sewerage infrastructure
      and catchment sources of faecal indicators.

PMID- 15850191
TI  - The impact of bird populations on the microbiological quality of bathing waters.
AB  - To ensure optimum quality at Bathing Waters, the control of diffuse sources of
      bacterial contamination is receiving increasing attention. As part of an
      initiative to improve the quality of the EU designated bathing waters on the
      Fylde Coast (North West England), a project was undertaken to quantify the faecal
      indicator load from birds and assess the significance on water quality. High bird
      counts are encountered on the Fylde Coast with gulls, feral pigeons and starlings
      being prominent. The piers at Blackpool make an attractive roost for starlings
      with numbers peaking at over 30,000 in late summer. Systematic recording of bird
      numbers and locations was undertaken during 2001/2. Estimates were also made of
      the daily faecal organism production by the different species. The spatial
      distribution of faecal organisms from the bird population was statistically
      linked to synoptic water quality data. This allowed estimates to be made of the
      contribution from birds to the faecal pollution load at the bathing waters. The
      work confirmed a statistically significant link between bird populations and
      water quality with a marked seasonal bias.

PMID- 15850192
TI  - Nutrient load estimation in nonpoint source pollution of Hong Kong region.
AB  - Red tides and eutrophication have been frequently observed over the past two
      decades in coastal waters around Hong Kong, which are caused by many factors and
      one of them is the nutrient from nonpoint source pollution (NSP). This paper
      concentrates on the nutrients carried by river flow from watersheds. Since there
      are no systematical data sets of nonpoint source pollution in Hong Kong, monthly
      river water quality measurements, rainfall and river flow data, land uses, and
      other related information are used to analyze the characteristics of NSP and
      estimate the nutrient loads for Hong Kong region. Main achievements are as
      follows: firstly, besides mean concentration for single land use, the concept of
      integrated mean concentration for mixed land uses was proposed and applied.
      Secondly, mean concentrations were carried out for different land uses
      (agriculture, town, grassland, shrubland and woodland), each Water Control Zone,
      and Hong Kong region. Thirdly, the annual nutrient loads were estimated, for the
      first time in this paper, with various methods for the whole area of Hong Kong,
      and about 8000 tons of TN and 1500 tons TP are transported into coastal waters
      from Hong Kong's land in 1998.

PMID- 15850193
TI  - Persistent pollutants urban rivers sediment survey: implications for pollution
      control.
AB  - The impacts of diffuse urban sources of pollution on watercourses are quantified.
      A survey of nine urban streams in Scotland for persistent pollutants in stream
      sediments is described, together with sediments from SUDS ponds. Determinands
      reported are: PAHs, total hydrocarbons, and toxic metals (As, Zn, Ni, Pb, Cu, Cr,
      Cd). Results highlight hydrocarbons as a major urban pollutant, and show
      significant sediment contamination by toxic metals. The metals that occurred in
      the highest concentrations varied across the nine streams, but Pb, Cr, Ni, Zn and
      Cu most frequently present exceeded sediment quality standards. The pattern of
      contamination by PAHs suggested that pyrolytic sources were more ubiquitous and
      present in greater quantities than oil spill sources in these urban catchments.
      Exceptions were the sites below industrial estates. The findings indicate that
      four levels of activity will be needed to control urban diffuse sources of
      pollution: reductions in quantities of toxic pollutants used by manufacturers in
      the motor and construction industries; housekeeping measures to minimise storage
      and handling risks for oil and chemicals; public engagement to minimise polluting
      activities such as dumping oil and chemicals, and private car use; use of SUDS
      technology, including retro-fits in the worst affected urban areas.

PMID- 15850194
TI  - An assessment of the impact of the proposed EU bathing water directive on Irish
      coastal bathing area compliance.
AB  - An assessment of the impact of the new microbial water quality standards of the
      proposed EU Bathing Water Directive on the classification of designated Irish
      coastal bathing areas is presented. The new standards are applied retrospectively
      to the microbial water quality results for the bathing seasons of 1999, 2000 and
      2001, and the outcome is compared with that recorded under the present Bathing
      Water Directive. A Microsoft EXCEL application was developed to generate the
      retrospective bathing area classifications according to the proposed Directive
      (Excellent, Good, Poor). It was found that the number of Irish coastal bathing
      areas not attaining 'Excellent' classification (as would be required at present
      for the Blue Flag award) was trebled; the number attaining 'Good' classification
      was increased by about 50%, and the number attracting 'Poor' classification
      (equivalent to 'Fail' under the present Directive) was increased nine-fold. Some
      of the shortcomings of the proposed Directive and suggestions for its revision
      are discussed.

PMID- 15850195
TI  - Diffuse inputs of nutrients to Dublin Bay.
AB  - The River Liffey is the main source of diffuse nutrients to Dublin Bay and
      accounts for some 85% of all riverine inputs. The total load from the various
      rivers has been calculated at some 6601 kg N d(1) and 748 kg P d(1), of which
      around 82% and 52% are in the form of DIN and phosphate respectively. Sewage
      discharge adds almost the same again to the load, with minor contributions from
      the sediments (which may simply be remineralising the particulates) and from
      nitrogen fixation. However, these inputs are very much less than those exchanged
      twice-daily by tidal action. These contributions are due to change very shortly
      with the advent of the new STW in Dublin, but the major change may be more in the
      speciation of the nutrients, and in particular the dissolved/particulate balance.

PMID- 15850196
TI  - Results of 10 years of monitoring nitrogen in the sandy regions in The
      Netherlands.
AB  - The effect of policy measures on agriculture and water quality with respect to
      nitrogen have been monitored on farms in the sandy regions since the early 1990s.
      Nitrogen surplus on dairy farms decreased by 100 kg/ha (30%) in the 1991-1999
      period due to demonstration projects and the implementation of MINAS, limiting
      farm gate balance surplus. Nitrogen surplus on arable farms has slightly
      decreased (30 kg/ha, i.e. 20%), probably because MINAS became mandatory for
      arable farms from 2001 onwards. About 25% of the farm-gate balance N surplus
      leached as nitrate into the upper metre of the groundwater. The NO3-N
      concentration decreased in the 1992-2001 period, but the decrease was larger for
      dairy farms (16 mg/l, 46%) than for arable farms (7.7 mg/l, 30%). Of the decrease
      in NO3-N concentration on dairy farms, 23% is caused by a decrease in N surplus,
      and 27% by environmental factors, such as a higher precipitation surplus, more
      wet soils and more peat soils in the second part of the monitoring period.
      However, unknown factors are responsible for 50% of the decrease.

PMID- 15850197
TI  - A procedure to define natural groundwater conditions of groundwater bodies in
      Germany.
AB  - Commissioned by Germany's Working Group of the Federal States on Water Problems
      (LAWA) the authors developed a procedure to define natural groundwater conditions
      from groundwater monitoring data. The distribution pattern of a specific
      groundwater parameter observed by a number of groundwater monitoring stations
      within a petrographically comparable groundwater typology is reproduced by two
      statistical distribution functions, representing the "natural" and "influenced"
      components. The range of natural groundwater concentrations is characterized by
      confidence intervals of the distribution function of the natural component. The
      applicability of the approach was established for four hydrochemically different
      groundwater typologies occurring throughout Germany. Based on groundwater
      monitoring data from 7920 groundwater monitoring stations, 15 different
      hydrochemical parameters were evaluated for each groundwater typology. For all
      investigated parameters the range of natural groundwater concentrations has been
      identified. According to the requirements of the EC Water Framework Directive
      (article 17) (WFD) this study is a basis for the German position to propose
      criteria for assessing a reference state for a "good groundwater chemical
      status".

PMID- 15850198
TI  - Assessment of nitrogen excess in an agricultural area using a nitrogen balance
      approach.
AB  - A pilot study has been initiated to develop an approach for quantification of
      nitrogen excesses from agricultural activities that involve greenhouse farming in
      Kumluca Plain, Turkey. Detailed calculations utilizing the nitrogen balance
      method (NBM) were carried out at nine different locations within the plain over a
      time period of one year. The major contributing factors and governing operative
      mechanisms taken into consideration were nitrogen application rates both as
      organic and chemical fertilizers, irrigation water application practices, and
      nitrogen uptake by plants. The adopted approach yielded valuable information such
      as plant nitrogen uptake efficiencies, excess nitrogen, leaching rates and
      leachate nitrogen concentrations. Further, a site specific multiple linear
      regression model has been developed to estimate the ratio
      (N(leachate)/N(groundwater)) as a function of independent variables: farming age,
      excess nitrogen application and SEEPAGE Index Number. The negative sign of the
      model parameters implies that the ratio (N(leachate)/N(groundwater)) decreases as
      values of the independent variables increase. The adopted approach and the
      obtained results can beneficially be applied to similar sites to establish basic
      parameters of irrigation and fertilizer application operations.

PMID- 15850199
TI  - Is the destabilisation of lake peipsi ecosystem caused by increased phosphorus
      loading or decreased nitrogen loading?
AB  - Lake Peipsi (3555 km2, mean depth 7.1 m) located on the border of Estonia and
      Russia is the largest transboundary lake in Europe. L. Peipsi consists of three
      parts. The shared largest northern part L. Peipsi s.s. (2611 km2, 8.3 m) and the
      southern L. Pihkva (708 km2, 3.8 m) which belongs mainly to Russia are connected
      by the river-shaped L. Lammijarv (236 km2, 2.5 m). The catchment area (44,245 km2
      without lake area) is shared between Estonia (33.3%), Russia (58.6%) and Latvia
      (8%). Intensive eutrophication of L. Peipsi started in the 1970s. The biomass of
      N2-fixing cyanobacteria was low at heavy nutrient loading in the 1980s. After the
      collapse of soviet-type agriculture in the early 1990s, the loading of nitrogen
      sharply decreased. A certain improvement of L. Peipsi s.s. was noticed at the
      beginning of the 1990s together with the temporary reduction of phosphorus
      loading from Estonian catchment while in recent years a destabilisation of the
      ecosystem has been observed. This deterioration has been expressed mainly as
      intensive blue-green blooms and fish-kills in summer. Reappearance of blooms has
      been explained by the decrease in N/P loading ratio due to reduced N discharge
      while in some periods increased phosphorus loading could have supported this
      trend.

PMID- 15850200
TI  - A novel method for evaluating bioavailability of polycyclic aromatic hydrocarbons
      in sediments of an urban stream.
AB  - Hydrophobic organic pollutants in urban wet weather discharges can accumulate in
      the sediments of receiving waters and may have adverse effects on the ecological
      system, especially on benthic organisms. Here, a novel method is developed for
      evaluating the bioavailability of such hydrophobic organic pollutants by
      considering the digestive guts in deposit-feeding polychaetes. We compared the
      amount of polycyclic aromatic hydrocarbons (PAHs) extracted by an organic solvent
      and by sodium dodecyl sulfate (SDS) solution (as a hypothetical digestive gut
      fluid of polychaetes) and interpreted the ratio of the two values as
      bioavailability. The sediment extracts were applied to bacterial acute toxicity
      tests and algal growth inhibition tests. Sediment samples were collected from an
      urban stream system receiving wet weather discharges. The bioavailability of the
      total amount of 12 PAHs in the sediments was in the range 14-38% based on the
      results from the GC/MS determination of the two different extracts. Lower
      molecular PAHs showed higher bioavailability compared to the higher molecular
      ones. The sediment extracts were shown to be toxic towards both algae and
      bacteria. The SDS extracts showed similar or higher toxicity in the two biotests
      compared to the organic solvent extracts in spite of their lower PAHs content.

PMID- 15850201
TI  - Nutrient emissions from diffuse and point sources into the River Danube and its
      main tributaries for the period of 1998-2000--results and problems.
AB  - Nutrient emissions by point and diffuse sources were estimated for 388 sub
      catchments of the Danube river basin for the period 1998-2000 by means of the
      Model MONERIS. For nitrogen total emissions of 684 kt/a N were estimated for the
      Danube basin. 80% of these emissions were caused by diffuse sources (mainly
      groundwater, urban areas and tile drainage). For phosphorus the emission was 57
      kt/a P, with a contribution of diffuse sources to this sum of 58%. The comparison
      of calculated and observed loads shows that the mean deviation for the
      investigated sub-catchments of the Danube river basin is 20% for dissolved
      inorganic nitrogen and 34% for phosphorus. The spatial resolution of the emission
      calculations allows the identification of regional hot spots and the derivation
      of specific regional measures to reduce the emissions into the Danube and
      consequently into the Western Black Sea.

PMID- 15850202
TI  - Management of regional German river catchments (REGFLUD) impact of nitrogen
      reduction measures on the nitrogen load in the River Ems and the River Rhine.
AB  - The REGFLUD-project, commissioned by Germany's Federal Research Ministry (BMBF),
      addresses the problem of reducing diffuse pollution from agricultural production.
      The objective of the project is the development and application of multi-criteria
      scientific methods, which are able to predict diffuse pollution in river basins
      subject to economic feasibility and social acceptability. The selected river
      basins (Ems and Rhine basins) cover a variety of landscape units with different
      hydrological, hydrogeological and socio-economic characteristics. This paper
      focuses on the analysis of the effects of certain policy measures to reduce
      diffuse pollution by nitrogen. For this purpose a model system consisting of an
      agricultural sector model, a water balance model and a residence
      time/denitrification model was developed and applied. First results indicate a
      wide range of annual nitrogen surpluses for the rural areas between less than 10
      kg N/ha up to 200 kg N/ha or more depending on the type and intensity of farming.
      Compared to the level of nitrogen surpluses the level of nitrogen inputs into the
      surface waters is relatively moderate because of degradation processes during
      transport in soil and groundwater. Policy impact analysis for a nitrogen tax and
      a limitation of the livestock density stress the importance of regionally
      tailored measures.

PMID- 15850203
TI  - GIS-based influence analysis of geomorphological properties on pollutant wash-off
      in agricultural area.
AB  - This study improves the estimation of the self-purification coefficient for
      runoff analysis of pollution load using geomorphological factors. Formerly, the
      assimilative capacity, K, was estimated using a single geomorphological factor,
      Horton's form ratio, St. Here, K was divided into two factors, namely, a
      watershed self-purification coefficient (K) and a watershed form ratio (S(f)).
      The watershed form ratio, S(f), is the equivalent stream density and is
      considered an index of accessibility of the pollution load to the water body.
      Even though Sf had shown a clear reciprocal relationship with K, in agricultural
      areas, there is a limitation that the K, estimated by using an S(f) only can't
      reflect the variability of land coverage characteristics and/or land use. In this
      study, a new geo-characteristic index (GCI), S(R), which is composed of Sf and
      weighted flow accumulation ratio (F(r)), is suggested. GIS and remote sensing
      technique were used to calculate S(f) and F(r). Interestingly, a clear reciprocal
      relationship exists between K and S(R), and this relationship seems to be
      stronger for agricultural areas, as urbanized areas have easier wash off due to
      the sewer network or paved surfaces.

PMID- 15850204
TI  - Statistical modelling of riverine nutrient sources and retention in the Lake
      Peipsi drainage basin.
AB  - Implementation of the Water Framework Directive calls for methodologies and tools
      to quantify nutrient losses from diffuse sources at a river basin district scale.
      Here, we examine the possibility of using a statistical model for source
      apportionment and retention of nutrients in a large transboundary drainage basin
      (44,000 km2). The model approach uses non-linear regression for simultaneous
      estimation of e.g. source strength, i.e. export coefficients to surface waters,
      for the different specified land-use or soil categories and retention
      coefficients for pollutants in a drainage basin. The model was tested on data
      from 26 water quality stations with corresponding sub-basin data, i.e., land
      cover, point sources and atmospheric deposition, from the Estonian part of the
      Lake Peipsi drainage basin. The model showed that it was statistically possible
      to derive reliable export coefficients (i.e. unit-area loads) for nitrogen on
      agricultural land and forests. Moreover, it was shown with simple empirical
      functions that lake retention was approximately 30-35% for both nitrogen and
      phosphorus and that the riverine retention was low for both nitrogen and
      phosphorus (approx. 10%). Results show that the MESAW model is a simple and
      powerful tool for simultaneous estimation of sources and retention of nutrient
      loads in a river basin.

PMID- 15850205
TI  - Modelling nitrate losses from agricultural activities on a national scale.
AB  - The Nitrogen Risk Assessment Model for Scotland (NIRAMS) has been developed as a
      screening tool for prediction of streamwater N concentrations draining from
      agricultural land in Scotland. The objective of the model is to be able to
      predict N concentrations for ungauged catchments, to fill gaps in monitoring data
      and provide guidance in relation to policy development. The model uses national
      land use, soils and meteorology data sets and has been developed within an
      ArcView GIS user interface. The model includes modules to calculate N inputs to
      the land, residual N remaining at the end of the growing season, weekly time
      series of leached N and transport of N at the catchment scale. The N leaching and
      transport are. controlled by hydrological modules, including a national water
      balance model and a catchment scale transport model. Preliminary testing of
      NIRAMS has been carried out on eight Scottish catchments, diverse in terms of
      geographic location as well as land use. The model is capable of predicting the
      correct mean level of stream N concentrations, as well as the basic
      characteristics of seasonal variation. As such the model can be of value for
      providing estimates of N concentrations in ungauged areas.

PMID- 15850206
TI  - Effect of uncertainties in agricultural working schedules and Monte-Carlo
      evaluation of the model input in basin-scale runoff model analysis of herbicides.
AB  - In the prediction of time-series concentrations of herbicides in river water with
      diffuse-pollution hydrological models, farming schedules (the dates of herbicide
      application and drainage of irrigation water from rice paddies) greatly affect
      the runoff behavior of the herbicides. For large catchments, obtaining precise
      data on farming schedules is impractical, and so the model input inevitably
      includes substantial uncertainty. This paper evaluates the effectiveness of using
      the Monte-Carlo method to generate sets of estimated farming schedules to use as
      input to a GIS-based basin-scale runoff model to predict the concentrations of
      paddy-farming herbicides in river water. The effects of using the Monte-Carlo
      method to compensate for uncertainty in the evaluated parameters for herbicide
      decomposition and sorption were also evaluated.

PMID- 15850207
TI  - Incorporating uncertainty into predictions of diffuse-source phosphorus transfers
      (using readily available data).
AB  - Phosphorus (P) is a limiting nutrient in many freshwater ecosystems and increases
      in its availability can lead to eutrophication. Effective management of P in
      freshwaters requires quantitative estimates of P supply from all significant
      sources. A simple GIS-based model, capable of predicting total diffuse source
      phosphorus export from catchments using readily available data, has been
      developed. The model is based on the idea of export coefficients but includes the
      effects of topography (slope and cumulative area), soil type (using the U.K.
      Hydrology of Soil Types (HOST) classification) and climate (hydrologically
      effective rainfall) as well as land use. Uncertainty in key model parameters is
      accounted for using Monte Carlo simulation which involves random sampling from
      probability density functions in a large number of iterations. This reduces the
      need for subjective optimisation of export coefficients. The model has been
      applied to the Greens Burn catchment, Scotland and predicts P exports within the
      confidence limits of the measured values.

PMID- 15850208
TI  - Propagation of uncertainty in diffuse pollution into water quality predictions:
      application to the River Dender in Flanders, Belgium.
AB  - The uncertainty of water quality predictions caused by uncertainty in the inputs
      related to emissions of diffuse pollution is analysed. An uncertainty analysis of
      the effects of diffuse pollution is essential to compare the cost and benefits of
      measures to lower those emissions. We focus on diffuse nitrate pollution due to
      fertiliser use. Using an efficient Monte Carlo method and Latin Hypercube
      sampling, the contribution to the overall uncertainty by each of the inputs is
      calculated. The modelling environment is ESWAT, an extension of SWAT, which
      allows for integral modelling of the water quantity and quality processes in
      river basins. The diffuse pollution sources are assessed by considering crop and
      soil processes. The crop simulations include growth, uptake of water and
      nutrients and several land management practices. The in-stream water quality
      model is based on QUAL2E. The spatial variability of the terrain strongly affects
      the non-point source pollution processes. The methodology is applied to the
      Dender basin in Belgium. Eight inputs have significant influence on the time that
      the nitrate content in the river is higher than 3 mg/l. The uncertainty analysis
      indicated wide uncertainty bounds (95% percentile bounds differ up to +/-50% from
      the average NO3 predictions).

PMID- 15850209
TI  - GIS-based quantification of future nutrient loads into Lake Peipsi/Chudskoe using
      qualitative regional development scenarios.
AB  - This study aims at the quantification of possible future nutrient loads into Lake
      Peipsi/Chudskoe under different economic development scenarios. This drainage
      basin is on the borders of Russia, Estonia and Latvia. The sudden disintegration
      of the Soviet Union in 1991 caused a collapse of agricultural economy, and
      consequently, a substantial decrease of diffuse and point-source nutrient
      emissions. For the future, uncertainties about economic development and the
      priorities that will be set for this region make it difficult to assess the
      consequences for river water quality and nutrient loads into the lake. We applied
      five integrated scenarios of future development of this transboundary region for
      the next twelve to fifteen years. Each scenario consists of a qualitative story
      line, which was translated into quantitative changes in the input variables for a
      geographical information system based nutrient transport model. This model
      calculates nutrient emissions, as well as transport and retention and the
      resulting nutrient loads into the lake. The model results show that the effects
      of the different development scenarios on nutrient loads are relatively limited
      over a time span of about 15 years. In general, a further reduction of nutrient
      loads is expected, except for a fast economic development scenario.

PMID- 15850210
TI  - Public participation to improve water resource management in Uzbekistan.
AB  - At present Uzbekistan uses about 42 km3 of transboundary river flow and 27 km3 of
      this is from the Amu Darya. Annual average flow entering the upper reaches of Amu
      Darya within Uzbekistan is over 60 x 10(9) m3, which is already contaminated, but
      significant adverse water quality changes occur downstream where the river is the
      main source of drinking water. After independence Uzbekistan made a commitment to
      transfer management of farms and the rural economy from the public sector to
      private hands. Living conditions have deteriorated severely throughout
      Uzbekistan, but rural areas have been hit hardest. Several studies and projects
      in Uzbekistan have adopted the integrated water management-based environmental
      approach. A structured public participation and consultation process was followed
      during these projects including a social and the environmental assessment. This
      paper presents the two case studies to illustrate the effects of uniting the
      potential of all interested participants to improve water management and
      environmental safety. Consultation between the two main groups of stakeholders is
      essential for the future of the water sector. There is substantial support for
      WUAs among all stakeholders, at all levels, including among those stakeholders
      who currently manage the existing system.

PMID- 15850211
TI  - Review of attitudes and awareness in the agricultural industry to diffuse
      pollution issues.
AB  - The Scottish Executive considers 'Diffuse Pollution from Agricultural
      Enterprises' as a priority issue over the next 5-10 years and recognises the need
      to improve knowledge transfer, advice and training amongst farmers, crofters,
      contractors and advisers. The Scottish Environment Protection Agency commissioned
      SAC to survey advisory staff on diffuse pollution issues, mitigation measures and
      delivery of environmental advice to the farming industry. This showed that the
      impact of agricultural diffuse pollution on the environment is considered a
      serious problem as is the future impact of legislation on farm business. There is
      an urgent requirement to raise advisers' awareness of environmental legislation
      and of mitigation measures. Advisers consider that farmers have limited awareness
      of diffuse pollution problems but those that do would consider the impact on the
      environment to be serious. There is a lack of knowledge on the effectiveness of
      pollution mitigation measures. Better technical information, supported by
      research, is required. This information is best conveyed to advisers via the
      internet, technical notes and directly by environmental specialists and delivered
      on to farmers by farm visits. Lack of funds prevents most farmers adopting best
      management practices and more than 80% of advisers consider that environmental
      advice should be free.

PMID- 15850213
TI  - A study of SS size distribution during runoff and fractionation of phosphates
      depending on soil size in agricultural watershed.
AB  - Characterization of the differences and algal-available fractions of P in soils,
      suspended solids, and bottom sediments have been the main topics of research
      during the past decade. However, the size distribution and properties of
      particulate matter in runoff have not been much studied in Japan. Here we study
      particle size distribution during runoff and the chemical characteristics of P in
      each soil size fraction and relate them to land use. The temporal variation of
      particulate sizes during rain events is different in each watershed. Most
      particles have the size in the range of 10-100 microm. Also, the percentage of
      BAP in TP as well as percentage of PCOD in SS also varies temporally and
      spatially during runoff. To investigate how soil particles characteristics depend
      on land use, soil samples from two watersheds are examined. For particle size
      distribution and specific gravity, no significant difference among watersheds is
      found. However, C, N, and P content are indirectly proportional to the particle
      size, which means smaller particle size results in larger. H2O-extracted P, NH4Cl
      extracted P, NAI-P, Apatite-P, Organic-P, and TP contents in each soil particle
      sample vary depending on particle size, land use, and watershed.

PMID- 15850212
TI  - Effects of water protection measures on the profitability of farms.
AB  - The effect of different management measures on the nutrient losses from crop and
      animal husbandry systems, in particular nitrogen, and on the total income of
      model farming enterprises was investigated. Such measures are considered as
      powerful options for meeting the requirements of "cross compliance" within the
      Agenda 2000 midterm review of the CAP. Optimisation of the storage and handling
      of animal manure was shown to be the most important and cost effective measure to
      reduce nutrient losses on farms. Other measures such as protein and phosphorus
      adapted feeding, maintaining a year-round cover crop on arable land and
      conservation tillage were also effective and it is recommended that these are
      adopted into farming practices. In general, measures that have both a high
      potential to reduce nutrient losses and are cheap to apply, and therefore have
      little effect on the overall profitability of farms, should be given priority in
      water protection policies.

PMID- 15850214
TI  - [Methods of experimental validation of potential target proteins for creation of
      new drugs].
AB  - Review is devoted to the description of the main existing and developing
      technologies for experimental validation of potential targets predicted in silico
      by comparative genomics and bioinformatics methods. Since this problem has not
      been solved yet, the description of a wide set of methods, suitable for the
      validation of potential targets, is given. The following questions have been
      considered: (1) applications of proteomic technologies (control of potential
      targets expression and their variability, analysis of protein-protein
      interactions); (2) use of genomics technologies in experimental validation of
      targets (inactivation of the target genes, suppression of transcription,
      inactivation of the target mRNA, suppression of translation); (3) methods of
      direct inactivation of target proteins (monoclonal antibodies, light
      inactivation, one-chain antibodies, intrabodies, aptamers); (4) high-throughput
      technologies; (5) targets validations in vivo.

PMID- 15850215
TI  - [No: a new look on the mechanism of action of old drugs].
AB  - The paper reviews the main approaches used for development of effective
      therapeutic means directly regulating signaling system "nitric oxide (NO)-
      soluble guanylate cyclase--cyclic guanosine monophosphate (cGMP)". Special
      attention is paid to the role of this system in the mechanism of action of so
      called "old drugs". Using new approaches for investigating the antihypertensive
      and anti-aggregatory action of NO and the role of guanylate cyclase in these
      processes the priority and fundamental data concerning the elaboration of the
      molecular basis of directed search and creation of new, effective
      antihypertensive and antiaggregatory compounds have been obtained. Studies of
      direct activation of soluble guanylate cyclase by the original NO-donors new
      activators of this enzyme resulted in discovery of new drugs participating in
      regulation of haemostasis and vascular tone. The priority data on new inhibitors
      of NO-dependent activation of guanylate cyclase (among which turn to the drugs)
      and the possible molecular mechanism of their pharmacological action are
      presented. It was shown at first time that the signaling system "NO-soluble
      guanylate cyclase-cGMP" may be involved in the mechanism of the therapeutic
      action of a number of widely used drugs including those acting as
      chemotherapeutics and antiprotozoics.

PMID- 15850216
TI  - [Statistical characteristics of inhomogeneities of protein and chromation
      networks].
AB  - Natural textures (networks) are observed in many cases: the inter-cellular
      contact sites, endoplasmic reticulum membranes etc. The vast amount of
      experimental data was analyzed to produce the distribution histograms for the
      length of the segments in the protein and chromatin networks of different origin.
      The networks both from the eukaryotic cells and nucleis, as well as from E. coli
      and viruses are presented. Statistical analysis demonstrated that all
      experimentally observed histograms fit to the following formula: F(x) = (5(5)[4])
      x x(4)x exp(-5x) where x =l/<l>, l- length of the network segment, and </> is the
      average length of the segment. In contrast to the Gaussian distribution, the
      distribution of the segments' lengths is markedly assymetrical. The shape of the
      distribution does not dependent on the origin of the analyzed network.

PMID- 15850217
TI  - [Using the mass spectrometry analysis for hepatitis C virus typing].
AB  - Determination of the hepatitis C virus (HCV) genotype has become the standard
      procedure in laboratory diagnostics of HCV infection. Genotype elucidation has
      prognostic value assignment helps in assessing disease prognosis and promotes
      establishing appropriate duration of treatment. Now 11 major genotypes and more
      than 70 subtypes of HCV have been identified using the sequence variability
      within 5' non-coding region (5' NCR). In Russia the most common subtypes are 1a,
      1b, 2a, 3a and more rare - 4 and 5 types. While the "gold standard" for testing
      is nucleic acid sequencing, a variety of other assays, including the line probe
      assay or type-specific amplification, has been developed to provide more rapid
      and cheaper forms of testing. The aim of this study was to determine the type
      specific single nucleotide polymorphism (SNP) in 5' NCR HCV by the classical
      three-step minisequencing method with followed MALDI-TOF mass spectrometry
      detection The fragments of 5'NCR of HCV genomes were amplified by the nested RT
      PCR. The removal of excess nucleotides and primers was performed. Three
      oligonucleotide primers were design to detect two sets of type-specific SNP in 5'
      NCR HCV. The primer extension reaction was performed using modified thermostable
      DNA polymerase and in the presence of ddNTP. The molecular weights of primers
      extension reaction products were analyzed using MALDI-TOF mass spectrometry. The
      HCV genotype was determined according the presence in analyses sample the
      molecules with expected molecular weights. The suggested method was used to type
      HCV from 69 HCV-positive sera. The 1a genotype was determine in 4.5% samples, 1b 
      48%, 2a - 4.5% 3a - 29%, 4 - 1.5%. The mixes of two genotypes were found in 13%
      samples. All data confirmed by direct nucleic acid sequence. Thus, the new method
      for HCV typing has been developed using the minisequencing reaction and mass
      spectrometry for the determination of nucleic acid molecular weight.

PMID- 15850218
TI  - [The regulatory action of dipeptide "Deglutam" on the glutamine metabolized
      enzymes in the carcinosarcoma SM-1 cells].
AB  - The influence of modified antineoplaston AS2-1 (with altered ratio of L
      phenylalanine and L-glutamine derivatives, "Deglutam") on the activity of
      glutamine synthetase, glutaminase isoforms in the carcinosarcoma SM-1, tumor
      weight, per cent of the inhibition of tumor growth and blood impact index was
      investigated in rats with carcinosarcoma SM-1. The preparation was administered
      in the dose of 125 mg/kg twice a day for 12 days (on the 7th day after tumor
      transplantation). Intensive growth of carcinosarcoma SM-1 was accompanied by
      activtion of the glutamine metabolizing enzymes. The dose-response effect of
      "Deglutam" on the studied enzymes depended on the mode of preparation
      administration. The intragastric administration of the preparation caused the
      same effect on the glutamine metabolizing of SM-1 cells; as it was earlier
      observed in rat liver. Administration of the modified preparation ANP AS2-1
      (containing L-glutamine derivatives) influences regulation of glutamine
      metabolism in carcinosarcoma SM-1 cells, possibly, due to formation of substrates
      in the tissues of the tumor-bearing body similar to glutamine. It is also
      possible that in the tumor tissues these enzymes have different affinity to
      glutamine. This may explain greater effectiveness of the synthetic preparation on
      the basis of L-glutamine derivatives rather than the amino acid itself.

PMID- 15850219
TI  - [The contents of ascorbic acid and its oxidized forms at the aging of red blood
      cells produced in conditions of the normal and intense of erythropoesis].
AB  - Levels of ascoroic acid, its oxidized forms, dehydroascorbic acid (DHA) and
      diketogulonic aci (DKGA), and the sum of all forms of ascorbic acid (SAA) were
      investigated in aging red blood cells produced under physiological and stress
      conditions (massive hemorrhage) Aging of red blood cells o intact animals is
      accompanied by accumulation of DKGA and decrease of AA, DHA and SAA
      concentrations. Comparison of these parameters between young and old red blood
      cells produced befor and after hemorrhage revealed decrease of AA concentration
      (52%) and accumulation of DKGA (27%) on the 7th day. On the 7th, 20th, 30th days
      after hemorrhage red blood cells are characterize by increased concentrations of
      DHA, DKGA, SAA with simultaneously decreased contents of the AA as compared with
      red blood cells of intact animals. Similar changes were the most pronounced o the
      7th day; on the 20th day they decreased and on the 30th day they returned to
      control levels.

PMID- 15850220
TI  - [The effects of divalent cations on the fibrin clot formation and its lysis].
AB  - Hemocoagulation is a Ca(2+)-dependent process, and we suppose that other bivalent
      cations (BC) can also influence this system. The effects of some BC (Ca2+, Fe2+,
      Zn2+, Cd2+, Co2+ and Ni2+) on thrombin-induced plasma clotting and clot lysis
      caused by streptokinase have been studied. All BC studied, except Fe2+,
      maintained the formation of fibrin clot followed by its lysis. In the presence of
      BC the coagulation part of the turbidimetry curve changed in a dose-dependen
      manner and was characterized by: (1) the decrease of the induction period which
      seems to be due to thrombin activation or accelerating fibrin self-association;
      (2) the elevation of the maximal optical density of the fibrin clot and the
      velocity of its achievement. The fibrinolytic part of the curve was characterized
      by the optical density downfall acceleration at low Co2+, Cd2+, Zn2+ and Ni2+
      concentrations but marked delay of the process at BC higher concentrations. So,
      ions of Co2+, Cd2+, Zn2+ and Ni2+ but not Fe2+ significantly influence the
      dynamics of thrombin-induced clot formation and optical clot characteristics. At
      different ion concentrations BC may activate or inhibit fibrinolysis.

PMID- 15850221
TI  - [Peculiarity of the antioxidant action of the extract from Aronia melanocarpa
      leaves antioxidant on the brain].
AB  - The antioxidant action of the extract from Aronia melanocarpa leaves on the brain
      was investigated. The intraperitoneal injection of extract in the dose of 0.2
      g/kg prevented manifestations of oxidative stress in the brain induced by
      immobilization of rats. In vitro experiments revealed that the extract decreased
      intensity of ascorbate--and H2O2 -induced lipid and protein peroxidation in the
      brain homogenates. The most effect of the extract on ascorbate--induced lipid
      peroxidation was found in the postmitochondrial fraction of brain homogenate.

PMID- 15850222
TI  - [Disfunction of thyroid gland at experimental hyperuricemia].
AB  - Thyroid gland function was investigated in rats with experimental hyperuricemia.
      Data obtained indicate that dyshormonal changes are secondary ones and their
      development depends on the state of purine metabolism. Administration of
      allopyrinol, an uric acid depressant drug, improved thyroid gland function.

PMID- 15850224
TI  - [GABA metabolism and contents of neuroactive amino acids in rat brain after acute
      morphine administration].
AB  - The activities of GABA-catabolizing enzymes (GABA-transaminase and succinic
      semialdehyde dehydrogenase), succinate dehydrogenase, alanine and aspartate amino
      transferases, the contents of GABA, glutamate, glutamine, alanine, aspartate and
      glycine were studied in rat brain regions after acute morphine administration.
      Intraperitoneal (i.p.) administration of 10 mg/kg morphine increased the
      glutamate level and decreased GABA and glycine levels in cortex. This may explain
      an excitable effect of morphine. When the higher doses of morphine were
      administered (20 and 40 mg/kg, i.p.), the most pronounced changes in the amino
      acids tested were observed in brain stem, possibly because of higher density of
      opiate receptors there. Decrease in glutamate level in the brain stem was
      accompanied by accumulation of its metabolic precursors glutamine and aspartate
      and decrease of inhibitory amino acids (GABA, glycine) leves, when the dose of 40
      mg/kg was used. The data obtained indicate a dose-dependent relationship between
      the parameters studied and behavioral action of morphine.

PMID- 15850223
TI  - [Functional activity of blood and liver cells under formaldehyde intoxication via
      inhalation].
AB  - The influence of formaldehyde (of 5 and 10 mg/m3) on the state of the antioxidant
      system the blood and liver of rats, the activity of pentose phosphate pathway
      enzymes, and weight of immune organs was investigated. Formaldehyde intoxication
      led to activation of lipid peroxidation processes in red blood cells and
      hepatocytes. In the liver cells these changes were accompanied by activation of
      the antioxidant and detoxification systems. Formaldehyde depleted thiamine
      diphosphate in the liver, and this effect was not dose-dependent. The number of
      blood cells remained unchanged. Formaldehyde at the concentration of 10 mg/m3
      exerted the negative effect on the thymus. This effect may be related to
      stimulation of lipid peroxidation.

PMID- 15850225
TI  - Marburg haemorrhagic fever, Angola--update.

PMID- 15850226
TI  - Standardization of the nomenclature for genetic characteristics of wild-type
      rubella viruses.
AB  - The main goals of the meeting--to provide guidelines for describing the major
      genetic groups of rubella virus and to establish uniform genetic analysis
      protocols--were achieved. Guidelines for describing the genotypes as an
      operational taxonomic group consisted of the designation of reference viruses and
      reference sequences for 7 genotypes of rubella viruses representing 2 clades, and
      designation of an additional 3 provisional genotypes. Provisional genotype status
      was given either because reference viruses were not yet available and/or because
      there was uncharacterized complexity within the genetic group. Uniform analysis
      protocols recommended the comparison of unknown viral sequences with the complete
      set of designated reference viruses, and recommended a minimum acceptable
      sequence window which produced phylogenetic results with high confidence values.
      A list of literature references about rubella virus phylogeny and molecular
      epidemiology is available from the WHO Internet site for this report. As
      additional understanding of the genetic characteristics of wild-type rubella
      viruses is achieved, updates to the recommended nomenclature will be made and
      published in the Weekly Epidemiological Record.

PMID- 15850227
TI  - A word on nutrition and HIV/AIDS.

PMID- 15850228
TI  - Sleep Deprivation, Hunger and Satiety Hormones, and Obesity.

PMID- 15850229
TI  - Nutrition assessment in HIV infection.
AB  - Nutrition assessment is a vital component of the general care of HIV-infected
      adults. With access to highly active antiretroviral therapy (HAART), HIV
      infection may become a chronic, manageable disease. Nutritional and metabolic
      complications traditionally associated with HIV infection such as
      hypertriglyceridemia, low levels of high-density lipoprotein (HDL) cholesterol,
      and weight loss continue to occur. However, emerging abnormalities such as
      regional alterations in body shape (fat re-distribution syndrome or HIV
      associated lipodystrophy), increasing body weight, high levels of low-density
      lipoprotein (LDL) cholesterol, insulin resistance, and other metabolic
      derangements may also be present. In addition, as patients are living longer,
      they may be susceptible to other age-related diseases such as diabetes,
      cardiovascular disease, and obesity. In this article, we review strategies for
      nutrition assessment and management in HIV-infected adults. Attention is focused
      on specific symptoms such as weight loss and diarrhea and specific disorders such
      as lipodystrophy, micronutrient deficiencies, and dyslipidemia, which commonly
      affect HIV-infected individuals. Proper attention to nutritional status may help
      to reduce the burden of disease and promote an enhanced quality of life in HIV
      infected individuals.

PMID- 15850230
TI  - Micronutrients and HIV disease: a review pre- and post-HAART.
AB  - Low serum micronutrient levels are common in HIV-positive individuals and have
      been associated with immune impairment, HIV disease progression, and increased
      mortality. Studies of micronutrient supplementation have yielded conflicting
      results, although several large trials suggest that multivitamin supplements, but
      not vitamin A, may decrease morbidity and mortality in some HIV-positive
      populations. Studies also suggest that antioxidant supplementation may decrease
      markers of oxidative stress in individuals with HIV, while selenium may enhance
      immune function by modulating cytokine production. Clearly, more research is
      needed, but current knowledge supports the use of a multivitamin supplement as a
      low-cost adjunct to antiretroviral treatment.

PMID- 15850231
TI  - Role of n-3 fatty acids in prevention of disease complications in patients with
      HIV.
AB  - Hypertriglyceridemia and insulin resistance have been seen in patients with HIV.
      Beneficial effects of the n-3 fatty acids eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) have been reported for these conditions. One study of
      n-3 fatty acid supplementation in patients with HIV reported a decrease in serum
      triglyceride levels. These marine fatty acids appear to be working at a number of
      sites to achieve an improvement in lipid metabolism and insulin sensitivity.
      There is disagreement about the amount of n-3 fatty acids needed to achieve
      different effects and about the optimal ratio of dietary n-6 and n-3 fatty acids.

PMID- 15850232
TI  - The role of nutrition in fat deposition and fat atrophy in patients with HIV.
AB  - HIV-associated body shape changes and metabolic abnormalities, called HIV
      associated lipodystrophy, are being seen with increased frequency. These issues
      may be associated with an increased risk of other diseases, such as
      cardiovascular disease, or with poor adherence to antiretroviral medications.
      Diet may be useful in the prevention and treatment of lipodystrophy and is a cost
      effective and non-toxic intervention. At present, there are limited data on
      nutrition and HIV-related body shape changes. The purpose of this article is to
      review the roles that diet may play in the development and treatment of fat
      deposition and fat atrophy.

PMID- 15850233
TI  - Dietary intake in HIV-positive persons with and without malabsorption.
AB  - This review examines the relationship among malabsorption, diarrhea, dietary
      intake, and body composition in an outpatient cohort of individuals with HIV
      infection. Twenty-three percent of the participants had malabsorption, which was
      not associated with the presence of current or chronic diarrhea. In this
      "outpatient" HIV cohort with a mean body-mass index (BMI) of 25 kg/m2, the
      presence of malabsorption did not have adverse nutritional outcomes in terms of
      body weight, lean body mass, hemoglobin, or albumin. The diets of those with or
      without malabsorption did not meet the goals of the Dietary Guidelines for
      Americans. Median dietary intake was high in percentage of total fat and
      saturated fat and low in total fiber intake and some key micronutrients.

PMID- 15850234
TI  - Nutrition and HIV in the international setting.
AB  - HIV infection has become increasingly prevalent globally, with more than 40
      million infected individuals worldwide, the majority of whom live in the resource
      limited world, especially sub-Saharan Africa and Asia. There are nutritional and
      metabolic issues that significantly impact morbidity and mortality in HIV
      infected populations. In addition, malnutrition has been associated with an
      increased risk of transmission of HIV from infected mothers to infants, and
      malnutrition may further compromise HIV-infected individuals who have
      tuberculosis or persistent diarrheal disease. The introduction of highly active
      antiretroviral therapy will have a significant impact on the mortality of HIV,
      but will not completely alleviate the malnutrition associated with HIV infection
      in the global setting.

PMID- 15850235
TI  - Patient information. Symptom management.

PMID- 15850236
TI  - Patient information. Omega-3 fatty acids: what? why? and how?

PMID- 15850237
TI  - Messing with mother nature.

PMID- 15850238
TI  - Cervical cancer screening.

PMID- 15850239
TI  - Physical therapy for back pain.

PMID- 15850240
TI  - 'Thanks for sharing': a fictional reflection on shared medical appointments.

PMID- 15850241
TI  - Highly resistant HIV: if not a super strain, at least a wake-up call.

PMID- 15850242
TI  - Management of erectile dysfunction by the primary care physician.
AB  - Erectile dysfunction is common and closely associated with age and risk factors
      for cardiovascular disease. The oral selective inhibitors of phosphodiesterase
      type 5 (PDE5) have become the treatments of choice, owing to their convenience,
      general safety, and broad-spectrum effectiveness. For the same reasons, they have
      greatly simplified the workup. Thus, the general practitioner has gradually
      replaced the urologist for the initial management of erectile dysfunction and the
      proper evaluation of cardiac status before starting treatment with the PDE5
      inhibitors. The following review provides a practical approach for the management
      of erectile dysfunction in primary care.

PMID- 15850243
TI  - Varicose veins: newer, better treatments available.
AB  - Varicose veins are not only a cosmetic annoyance: they can lead to complications
      that result in lost time from work and lost wages. Treatment has improved with
      the use of minimally invasive techniques that reduce recovery time and
      complications and offer better long-term results--encouraging news, considering
      that the problem affects 10% to 20% of adult men and 25% to 33% of adult women.

PMID- 15850244
TI  - Uveitis in the internist's office: are a patient's eye symptoms serious?
AB  - Uveitis is an inflammatory process that may affect one or several specific areas
      of the eye. But when a patient presents to an internist with eye symptoms, be it
      photophobia, "floaters," or red eye, the diagnosis is not always clear. If the
      diagnosis of uveitis is made, internists must search for an underlying cause,
      such as infection or an autoimmune disease.

PMID- 15850245
TI  - Advances in the treatment of hemorrhagic stroke: a possible new treatment.
AB  - Recombinant factor VIIa may be the first proven treatment for intracerebral
      hemorrhage (ICH); to be effective, it must be given soon after the onset of
      symptoms. Surgical removal of the hematoma by craniotomy at about 24 hours does
      not appear to offer much benefit compared with conservative therapy and delayed
      surgery, except possibly for superficial ICHs. Standardized management of medical
      complications remains important. New randomized treatment trials of recombinant
      factor VII and surgery are in progress or just beginning.

PMID- 15850246
TI  - Hypertensive disorders of pregnancy: overdiagnosis is appropriate.
AB  - Hypertensive disorders of pregnancy are common and require special care to
      prevent maternal and fetal morbidity and mortality. Since the symptoms of
      preeclampsia, the most dangerous disorder, are variable, overdiagnosis is
      appropriate. Chronic hypertension complicates 5% of all pregnancies and is
      becoming more common due to delayed childbearing.

PMID- 15850247
TI  - An elderly woman with leg swelling and pain.

PMID- 15850248
TI  - [H1 antihistamines. Actions, adverse effects, administration].

PMID- 15850249
TI  - [Acne vulgaris].

PMID- 15850251
TI  - [Malaria: standby medication or chemoprophylaxis?].

PMID- 15850252
TI  - Does the UK need to go to China to find nurses?

PMID- 15850250
TI  - [Warts].

PMID- 15850254
TI  - Alison Gadsby a voice from mental health.

PMID- 15850253
TI  - Nurse regulation in the spotlight.

PMID- 15850255
TI  - Palliative care: meeting the needs of dying patients.

PMID- 15850256
TI  - All in a day's work.

PMID- 15850257
TI  - Using the matron's charter to improve hospital cleaning.
AB  - The new Matron's Charter places the responsibility of cleaning wards and
      equipment firmly within the remit of the matron. The matron can lead innovations
      that promote and empower staff to take control of their environment by using the
      simple, effective methods discussed in this article.

PMID- 15850258
TI  - Hunter syndrome.

PMID- 15850259
TI  - Ensuring appropriate use of blood transfusion in anaemia.
AB  - Recent concerns over the blood transfusion service have highlighted the
      importance of ensuring that transfusion practice is safe and effective. One area
      of concern is the inappropriate use of red cell transfusions in patients
      presenting with anaemia, which unnecessarily exposes patients to transfusion
      risks and fails to address the underlying cause of the condition. This article
      reports on the development of an algorithm to help clinicians make decisions on
      the use of red cell transfusion.

PMID- 15850260
TI  - How a clinical coordinator improved emergency care.
AB  - A clinical ward coordinator role was developed within an emergency admissions
      ward. The aim was to reduce each patient's length of stay on the admissions ward
      and the waiting time for a bed in the emergency areas.

PMID- 15850261
TI  - Ibuprofen.

PMID- 15850262
TI  - The validity of treating people with a personality disorder.
AB  - Within the field of mental health there are few areas as controversial as that of
      personality disorder. This article examines the categorisation and treatment of
      people with a personality disorder in addition to looking at the possible reasons
      for health care professionals' perceived inability to deal with this client
      group.

PMID- 15850263
TI  - Improving the detection of polycystic ovary syndrome.

PMID- 15850264
TI  - IV nursing in the patient's home.

PMID- 15850265
TI  - Primary care takes the lead in health.

PMID- 15850266
TI  - [Diagnosis and therapy of lung neoplasms. Interdisciplinary guidelines].

PMID- 15850267
TI  - [2 patients with signs of venous thromboemolism: deviations from the guidelines].
AB  - Deviations from the relevant guidelines occurred during the diagnosis of 2
      patients with clinical signs of venous thromboembolism (VTE). In a 73-year-old
      man with bladder cancer and dyspnoea in whom pulmonary embolism was suspected,
      pulmonary angiography was not performed following a negative
      ventilation/perfusion scan; instead, a less invasive spiral CT scan was
      performed. Because the communicated outcome of 'pulmonary embolism' was
      incorrect, the patient was treated with anticoagulants and began bleeding from a
      duodenal ulcer. In a 32-year-old man with minor clinical signs of deep-vein
      thrombosis in his right leg, additional investigation was not pursued following
      negative echography. After 3 weeks, the thrombosis was extensive and pulmonary
      embolism developed, and it appeared that there was a family history of VTE. Both
      patients were later adequately diagnosed and treated. Guidelines are increasingly
      used in legal matters as a gauge in the assessment of medical care. Physicians
      and hospital directors are responsible for a policy on guidelines and the
      (possible) compliance therewith. Physicians should and must deviate from
      guidelines if there are good reasons. They must justify the deviation from
      protocol in the medical records.

PMID- 15850268
TI  - [Optimising patient isolation due to methicllin-resistant Staphylococcus aureus].
AB  - Isolation of patients is used to control the spread of certain microorganisms in
      the hospital, e.g. meticillin-resistant Staphylococcus aureus (MRSA). Recent
      investigations have shown that the quality of care for patients in isolation is
      affected significantly. However, this is not accompanied by an effect on the
      morbidity or mortality. The successful Dutch policy on MRSA is based largely on
      strict isolation of patients colonised with MRSA. If MRSA becomes endemic, this
      is accompanied by increases in morbidity and mortality as well as costs. The
      disadvantages of isolation are recognised and should be prevented as far as
      possible. New diagnostic and therapeutic developments can shorten the duration of
      isolation significantly, which will further improve the quality of care.

PMID- 15850269
TI  - [Screening for coeliac disease currently not indicated].
AB  - Coeliac disease is a common disorder, but most persons with coeliac disease
      remain undetected because they have only mild aspecific symptoms or are free of
      symptoms. For a definitive diagnosis small bowel biopsies showing partial or
      (sub)total villous atrophy are required. The presence of anti-endomysium and/or
      anti-tissue-transglutaminase antibodies in serum is strongly predictive for
      coeliac disease. In case of clear clinical suspicion the most straightforward way
      to diagnose or exclude coeliac disease is by taking endoscopic biopsies from the
      distal duodenum. When the suspicion is low, determination of the above mentioned
      antibodies as a first step suffices. At present there are insufficient reasons to
      initiate population-wide screening for coeliac disease by means of serological
      testing or individual screening by taking duodenal biopsies during each
      gastroscopy.

PMID- 15850270
TI  - [Clinical reasoning and decision-marking in practice. A general practitioner with
      long-standing anaemia].
AB  - In order to calibrate his haemoglobin meter, a general practitioner had his own
      haemoglobin level checked regularly at a nearby laboratory. At 37 years of age,
      one of these assays revealed 7,0 mmol/l. Because he had no symptoms, he
      prescribed himself iron-substitution therapy but the haemoglobin concentration
      did not normalise. At 52 years of age, the patient increasingly suffered from
      fatigue and exertional dyspnoea and had intermittent abdominal pain, distension
      and rumbling. Biopsies of the small intestine revealed crypt hypertrophy and
      intraepithelial lymphocytosis: signs ofcoeliac disease. The symptoms disappeared
      when the patient started to use a gluten-free diet. The haemoglobin level also
      normalised. Coeliac disease must be considered in the differential diagnosis of
      iron-deficiency anaemia.

PMID- 15850271
TI  - [Modern treatment methods for multiple myeloma: guidelines from the Dutch Haemato
      Oncology Association (HOVON)].
AB  - The treatment for multiple myeloma has undergone many changes over the past
      decade. Intensive therapy with autologous stem-cell support has improved the
      clinical outcome significantly in younger patients. Reduced intensity
      conditioning regimens have lowered the high treatment-related mortality of
      myeloablative allogeneic transplantation. New effective anti-myeloma drugs such
      as bortezomib and thalidomide analogues have become available. These new
      developments have made it necessary to formulate recommendations to facilitate
      decisions concerning the management of myeloma patients. The Myeloma Working
      Party of the Dutch Haemato-Oncology Association (Stichting Haemato-Oncologie voor
      Volwassenen Nederland) has developed therapy guidelines based on phase-II and
      phase-III studies as well as the expertise of the working party. These include
      upfront induction therapy followed by autologous transplantation for patients
      aged up to 65 years and oral melphalanprednisone treatment for patients with
      severe co-morbidities and patients over the age of 65 years. Patients under the
      age of 66 with an HLA-identical (family) donor are candidates for non
      myeloablative stem-cell transplantation following autologous stem-cell
      transplantation. For second-line treatment, thalidomide, combined with
      dexamethasone is recommended. Younger patients responding to second-line
      treatment are candidates for a second autologous transplant. Bortezomib is
      indicated for those patients refractory to the previous two lines of treatment.
      All patients should receive long-term bisphosphonates. Erythropoietin may be
      considered in symptomatic anaemia as well as antibiotic prophylaxis during
      induction therapy which includes dexamethasone.

PMID- 15850272
TI  - [Diagnostic image (235). A woman with a tumour on the thorax].
AB  - An 81-year-old woman presented with a tumour on the right hemithorax due to
      transthoracic progression of an intrathoracic reactivated tuberculosis infection.

PMID- 15850273
TI  - [Female professors in medicine in 2003: appointment, duties and family life].
AB  - OBJECTIVE: To inventory (a) how and when female professors of medicine were
      appointed, (b) how they combined their work with family life, (c) which changes
      in health care female and male professors expected as a consequence of the
      increasing number of women physicians, and (d) which changes they wished to see
      for their successors. DESIGN: Descriptive. METHOD: A questionnaire was used to
      collect data from the female professors of medicine who worked in the Netherlands
      as of 1 January 2003 (n = 43), and from the same number of male professors of
      medicine, who were matched for age and speciality. RESULTS: 39 women and 39 men
      responded (91%). The women were more often appointed after a closed application
      procedure (69 versus 51%). Two fifths of the women had a part-time appointment as
      professor, but they worked at least 45 hours per week. Women were more often
      present in educational committees than in selection committees. At the time of
      their appointment most women had no children (n = 16) or children who did not
      live at home (n = 7); the other 16 (41%) had children at home, as did 33 (85%) of
      the male professors. Over half of the 23 women with children were at home for at
      least 2 half-days per week when the children were young and in some cases the
      partners cared for the children full-time; the opposite was found among the 35
      men with children. A quarter of both mothers and fathers was present for
      activities of their children, like soccer training and final swimming tests,
      during office hours. The most important recommendations regarding the appointment
      and the functioning of professors concerned the structure and flexibility of
      medical education, the carefulness when considering appointments, and the
      possibilities to work part-time and to have a family life.

PMID- 15850274
TI  - [Three infants with constipation and muscular weakness: infantile botulism].
AB  - Two previously healthy infants, a boy of 10 weeks and a girl of 4 months
      presented with apathy and muscle weakness. A third previously healthy child, a
      girl of 6 weeks old was admitted with respiratory insufficiency. None of the
      three had had a bowel movement for a number of days. After extensive
      investigations which revealed few abnormalities Clostridium botulinum toxin was
      obtained in serum from all three children. Type-B-toxin was shown in the faeces
      of the older girl and boy; both recovered quickly. The other girl had type-A
      toxin; she died. Two of the three children were given honey to comfort them.
      Infantile botulism must be considered in every infant with symptoms of
      constipation and hypotonia. The diagnosis can quickly be confirmed by
      electromyography with repetitive 50-Hz-stimulation. Honey is a well-known source
      of the C. botulinum spore and should not be given to children under the age of 12
      months. These three children are the first cases to be described in the
      Netherlands.

PMID- 15850275
TI  - [The treatment of chronic hepatitis C virus infection in children].
AB  - A 9-year-old boy, a 15-year-old boy, and a 6-year-old girl were infected with
      chronic hepatitis C virus (HCV). They had no physical complaints and a virus
      genotype that was favourable to treatment with peginterferon-alpha and ribavirin.
      The younger boy and the girl had liver fibrosis and were treated for 6 months;
      the virus was eradicated from the boy's plasma and the fibrosis diminished, while
      the girl's plasma virus was again present shortly after the end of treatment. In
      the older boy with no fibrosis, treatment was temporarily suspended due to
      behaviour problems. HCV infection is a frequent cause of chronic hepatitis in
      children. A better understanding of its natural history, improvements in the
      efficacy of treatment, and more favourable outcomes seen in children compared
      with adults have gradually changed the consideration to treat children with
      chronic HCV infection over the last 10 years. The decision whether or not to
      treat depends primarily on the degree of liver damage, virus genotype, and the
      psychological condition and motivation of the patient. Screening patients at risk
      for chronic HCV infection and careful follow-up for liver damage in those with
      HCV infection have become even more important given the new insights regarding
      treatment.

PMID- 15850276
TI  - [The treatment of patients with gastric carcinoma based on the results of Dutch
      studies].

PMID- 15850277
TI  - Mast cell infiltration associated with tubulointerstitial fibrosis in chronic
      Aristolochic Acid Nephropathy.
AB  - Aristolochic Acid Nephropathy (AAN) is regarded as a kind of toxic nephropathy
      caused by the formation of DNA- aristolochic acid adducts in renal parenchymal
      cells. However, the underlying mechanisms driving the progression of renal
      interstitial fibrosis in AAN still remains unclear. This study aims to elucidate
      the role of some immunological factors, especially mast cells (MCs), in the
      pathogenesis of AAN. Sixteen patients with AAN were enrolled in this study,
      including five acute and 11 chronic AAN. Monoclonal antibodies against human
      tryptase, alpha smooth muscle actin (alpha-SMA), and CD68 were applied on serial
      sections, which were further counterstained with Periodic Acid-Schiff. It was
      found that massive tryptase-positive MCs were observed in the fibrotic areas in
      chronic AAN, especially around thickened tubular basement membranes where
      myofibroblasts accumulated too. In contrast, MCs infiltrated to a less extent in
      acute AAN, and were barely found in normal control kidneys. In chronic AAN, the
      number of MCs in the tubulointerstitium was positively correlated with the degree
      of renal fibrosis (r=0.64, P <0.05), but not with serum creatinine levels.
      Meanwhile, the recruitment of MCs into the renal interstitium is accompanied with
      local proliferation of myofibroblasts. Macrophages were not abundant, neither in
      acute nor in chronic AAN. Our findings show for the first time that mast cell
      infiltration seems to be associated with the progression of fibrosis in the renal
      tubulointerstitium in chronic AAN.

PMID- 15850278
TI  - Acute poisoning cases admitted to a university hospital emergency department in
      Diyarbakir, Turkey.
AB  - AIM: This study was conducted to determine the biological effects of acute
      poisoning, the nature of agents involved and the pattern of poisoning in
      Diyarbakir City, in the Southeast Anatolian region of Turkey, during 2000.
      METHOD: Hospital records of all admissions to the Emergency Department (ED) of
      Dicle University Hospital following acute poisoning were revised and all data
      from January to December 2000 were analysed. The present study included 44
      (25.9%) male (M) and 126 (74.1%) female (F), a total of 170 patients. The M/F
      ratio was 1.0/3.5. RESULTS: The mean age of patients was 23.3+/-6.3 years; 63
      (37.1%) of them were under 20 years of age and 147 (86.5%) were under 30 years of
      age. Most intoxication cases occurred during the summer season (93 of 170
      patients). On a monthly basis, admissions during April, May and July were most
      common (24, 26 and 30 patients, respectively). Sixty-two (36.5%) cases involved
      accidental poisoning while 108 (63.5%) involved deliberate poisoning. In suicide
      attempts, intoxications were more common in females (77 cases, 71.3%, P < 0.05),
      and in unmarried persons (74 cases, 68.5%, P < 0.05). There were only two deaths
      (1.2%) among the 170 admissions of acute poisonings. One of the deaths was due to
      pesticide poisoning and the other was due to medical drug abuse. Tachycardia (59,
      34.7%), vomiting (55, 32.4%) and loss of consciousness (42, 24.7%) were
      frequently observed, whereas hypersecretion (15, 8.8%), bradycardia (5, 2.9%),
      convulsion (8, 4.7%) and hypertension (2, 1.2%) were less frequent. Among
      pesticide poisoning cases the incidence of convulsion (6, 10.2%), miosis (6,
      10.2%), and hypersecretion (12, 20.3%) were significantly higher when compared to
      other cases (P=0.018, P <0.0001 and P <0.0001, respectively). CONCLUSION: In the
      Southeast Anatolian region of Turkey, pesticide intoxication is common especially
      among young, unmarried females and most of these intoxications are intentional
      self-poisonings. The annual rate of poisoning-related ED visits and mortality
      were found to be within expected ranges; psychoactive agents being the most
      common cause.

PMID- 15850279
TI  - Formate kinetics in methanol poisoning.
AB  - OBJECTIVE: The objective is to describe the kinetics of formate, the main toxic
      metabolite of methanol, in a series of consecutive patients treated in the same
      intensive care unit for severe methanol poisoning. METHODS: The charts of the
      patients admitted between 1987 and 2001 were reviewed. Inclusion criteria were: a
      history of deliberate methanol ingestion, with a blood methanol concentration
      greater than 20 mg/dL (6.2 mmol/L) or a high anion gap metabolic acidosis.
      Indications for hemodialysis were: blood methanol concentration >50 mg/dL (15.8
      mmol/L), metabolic acidosis (bicarbonate <15 mmol/L, arterial pH <7.30), visual
      toxicity. Antidotal therapy included ethanol administration in 22 cases, and
      fomepizole in three cases. Serial blood measurements were obtained for pH,
      bicarbonate, methanol and formate. Endogenous and hemodialysis elimination half
      lives were calculated as t1/2 =0.693/Ke. Fick principle was applied for
      hemodialysis clearance calculation. RESULTS: The records of 25 methanol poisoned
      patients were analysed. Among them, 18 patients had sufficient data to allow
      accurate determinations of formate kinetics. Formate half-life elimination during
      hemodialysis was 1.80+/-0.78 h, which was statistically different from the values
      observed before or in the absence of dialysis (6.04+/-3.26 h, P =0.004). The mean
      hemodialysis formate clearance rate calculated in eight cases was 176+/-43
      mL/min. A rebound in plasma formate concentration was observed in three patients
      after the discontinuation of hemodialysis. CONCLUSIONS: In accordance with
      previous isolated case reports and in contrast with a recent case series, our
      data document that hemodiaysis is effective in reducing formate elimination half
      life. The impact on clinical outcome is still debatable.

PMID- 15850280
TI  - Impact of polychlorinated biphenyl Aroclor 1254 on testicular antioxidant system
      in adult rats.
AB  - To clarify the reproductive toxicity of polychlorinated biphenyl compounds
      through determination of testicular lipid peroxidation, reactive oxygen species
      and enzymatic and non-enzymatic antioxidants in rats exposed to Aroclor 1254.
      Adult male rats were administered Aroclor 1254 at a dose of 2 mg/kg per day ip
      for 30 days. The rats were sacrificed 24 hours after last dosing and the serum
      and other tissues collected and processed for relevant determinations. The body
      weight and the weights of the testis, epididymis, ventral prostate and seminal
      vesicle and the serum testosterone and estradiol were significantly decreased in
      Aroclor 1254 treated rats. The testicular lipid peroxidation, hydrogen peroxide
      and hydroxyl radical were significantly elevated whereas, testicular antioxidant
      enzymes, including superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPX), glutathione-S-transferase (GST) and glutathione reductase (GR)
      were significantly decreased. The non-enzymatic antioxidants, vitamin C and
      vitamin E, were also decreased. These results suggest that Aroclor 1254 induces
      an increase in the lipid peroxidation, hydrogen peroxide and hydroxyl radical and
      diminish in the antioxidant defense system in rats, indicating that the free
      radical-dependent mechanism may play an important role in the testicular toxicity
      of polychlorinated biphenyls.

PMID- 15850281
TI  - Immunotoxicity evaluation of nelfinavir in rats.
AB  - The objective of these investigations was to determine whether exposure to the
      HIV-1 protease inhibitor nelfinavir compromises immune function in Sprague Dawley
      rats. Animals (20/sex per group) were exposed orally for 1 or 6 months to
      nelfinavir at doses of 0 (1% carboxymethylcellulose vehicle), 100, 300 or 1000
      mg/kg per day. Animals were observed daily for morbidity/mortality and for
      clinical signs of toxicity. Body weights were recorded weekly (weeks 1-14) and
      then monthly thereafter and at study termination. At termination (1 month or 6
      months; 10/sex per group), serum was collected and retained for toxicokinetic
      analysis. The spleen, thymus and liver were removed from each animal and weighed;
      thymuses and liver were discarded after weighing. Spleens were prepared and
      immunophenotyping, natural killer (NK) cell activity, and proliferative responses
      to mitogenic stimuli (e.g., concanavalin A, Salmonella typhimurium) were
      evaluated. There were no treatment-related effects on immune cell populations
      (absolute or percent values) or in proliferative responses. At the 1-month
      interval, a decrease in NK cell activity (0.45-fold control) was noted in male
      rats at 100 and 1000 mg/kg per day but not at the middle dose of 300 mg/kg per
      day. Female rats at 1 month were noted for an increase in NK cell activity (1.4
      fold control) at 100 mg/kg per day, but there was no difference in the NK
      response between vehicle-treated animals and those exposed to higher doses of
      nelfinavir. No effects on NK activity were noted in female animals after 6 months
      of nelfinavir treatment. Assay difficulties prevented evaluation of male rats at
      the 6-month interval. Taken together, the absence of a dose-response effect for
      NK activity in male rats treated for 1 month, the lack of suppressive effects in
      females treated for either 1 or 6 months, and the unchanged splenic NK cell
      numbers in nelfinavir-treated animals at both 1 and 6 months suggest that the
      decreased NK activity noted in male rats at 1 month is not biologically relevant.
      It was therefore concluded that, under the experimental conditions used, oral
      treatment with nelfinavir for 1 or 6 months at doses up to 1000 mg/ kg per day is
      not immunosuppressive in rats. C8hr values following nelfinavir treatment at 1000
      mg/kg per day for 6 months were between 1- and 2.7-fold the reported Cmax values
      in humans.

PMID- 15850282
TI  - Effects of chronic ingestion of sodium fluoride on myocardium in a second
      generation of rats.
AB  - Possible effects of long term exposure (6 months) to sodium fluoride (NaF)
      through drinking water on the morphology and biochemistry of myocardial tissue in
      second generation adult male rats were investigated. Wistar strain female and
      male rats were reared until the second generation of rats obtained, during which
      they were given 1, 10, 50 and 100 mg/L NaF in drinking water. Of the second
      generation, 28 male rats were divided into four groups and had the same
      treatment. All the second generation rats were sacrificed and autopsied at the
      end of the 6 months. In the samples of myocardial tissues, the levels of serum
      fluoride and the activities of principal antioxidant enzymes were determined, and
      a histopathological examination was conducted. Significant histopathological
      changes were found in the myocardial tissue of rats treated with 50 and 100 mg/L
      NaF. These were myocardial cell necrosis, extensive cytoplasmic vacuole
      formation, nucleus dissolution in myosits, swollen and clumped myocardial fibers,
      fibrillolysis, interstitial oedema, small hemorrhagic areas and hyperaemic
      vessels. Additionally, the increased activities of superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px), catalase (CAT) and thiobarbituric acid-reactive
      substance (TBARS) levels were observed in the myocardial tissues of rats treated
      with 10 and 50 mg/L NaF. On the other hand, the activities of SOD, GSH-Px, and
      CAT decreased, but the TBARS levels increased in the myocardial tissues of rats
      treated with 100 mg/L. The present results revealed that prolonged ingestion of
      fluoride through drinking water, particularly with high doses, induced
      significant histopathological and biochemical changes leading to myocardial
      tissue damage.

PMID- 15850283
TI  - A competitive ELISA detecting 7-methylguanosine adduct induced by N
      nitrosodimethylamine exposure.
AB  - N-Nitrosodimethylamine is a chemical compound known to be carcinogenic to animals
      and probably to humans. It is widespread and it can be found in food, tobacco
      smoke and in industrial emissions, such as in the rubber industry. N
      Nitrosodimethylamine exerts its biological effects after metabolic activation by
      forming methylating nucleic acids in DNA. The most formed adduct is 7
      methylguanosine. Our laboratory has developed and validated a competitive enzyme
      linked immunosorbent assay in order to detect this adduct in DNA exposed to N
      nitrosodimethylamine in vitro or in vivo. The imidazole ring-opening (iro) of 7
      methylguanosine was required because of its stability. When 7-methylguanosine iro
      and serum were incubated at 4 degrees C, the assay was 35 times more sensitive
      than at 37 degrees C (50% inhibition at 37 fmol 7-methylguanosine iro per well at
      4 degrees C and 1.28 pmol at 37 degrees C) with a lower limit of detection at
      1.58 fmol 7-methylguanosine iro. This assay is reproducible, can be routinely
      performed and is sensitive enough to detect 7-methylguanosine adduct in DNA
      samples from human exposed to N-nitrosodimethylamine. We aim to use this method
      in further studies on epidemiological assessment in people at high risk, such as
      smokers.

PMID- 15850284
TI  - Investigations on the subchronic toxicity of 2-methoxypropanol-1(acetate) in
      rats.
AB  - Wistar rats were exposed to 2-methoxypropylacetate-1 (2-MPAc-1) vapours in
      concentrations of 0, 110, 560 and 2800 ppm for (equiv. to 0; 0.6; 3.0 and 14.9
      mg/L) for 4 weeks in chambers (6 hours/day; 5 days/week; five male and five
      female animals per group). The top concentration was equivalent to a 95% vapour
      saturation at 20 degrees C and the animals reacted to this with a moderate
      respiratory irritation during the 6 hours exposure times; at 560 ppm these
      effects were only slight. The top dose was also associated with a significantly
      reduced body weight development and some hematologic and biochemical alterations
      of little specificity. The most prominent effect was thymic atrophy. No effects
      were noted on the testes or on the cellularity in blood or bone marrow. 560 ppm
      were without systemic effects. Furthermore, 2-methoxypropanol-1 (2-MP-1), 2-MPAc
      1 and 2-ethoxyethanol (EE) were administered in parallel by gavage to groups of
      five male Wistar rats daily for 10 days at near equimolar dose levels (1800, 2600
      and 1800 mg/kg per day, respectively). At the end of the administration period
      the testes were investigated. There was a pronounced testicular atrophy in
      animals exposed to EE, whereas no adverse effects were observed with 2-MP-1 and 2
      MPAc-1. The results of these studies indicate that 2-MP-1 and 2-MPAc-1 which
      previously had been shown to exert pronounced prenatal toxicity in rabbits and
      weak prenatal effects in rats are devoid of other forms of systemic toxicity in
      rats that are typically observed with ethoxyethanol and methoxyethanol.

PMID- 15850285
TI  - Design of peptides for thin films, coatings and microcapsules for applications in
      biotechnology.
AB  - A highly-interdisciplinary approach has been developed for minimizing the
      immunogenicity of films, coatings, microcapsules and other nano-structured
      materials fabricated from designed polypeptide chains. It is to base the amino
      acid sequences on solvent-exposed regions in the folded states of proteins from
      the same organism. Each such region that meets defined criteria with respect to
      charge is called a sequence motif. The approach becomes more specifically
      tailored for intravenous applications by requiring an employed sequence motif to
      correspond to a known blood protein. An algorithm has been developed to identify
      sequence motifs in protein-encoding regions of a genome. This work is focused on
      sequence motifs of charge per unit length >0.5 at neutral pH. It has been found
      that the number of unique sequence motifs meeting this criterion in available
      human genome data is maximal for motifs of approx. 7 residues in length. We have
      designed polypeptides on the basis of computational analysis and shown that they
      can be used to fabricate nano-structured thin films by electrostatic layer-by
      layer assembly (ELBL). The results of this work are discussed with a view to
      possible applications in biotechnology, notably development of biocompatible
      coatings and microcapsules.

PMID- 15850286
TI  - Cell viability of chitosan-containing semi-interpenetrated hydrogels based on PCL
      PEG-PCL diacrylate macromer.
AB  - Chitosan-modified biodegradable hydrogels were prepared by UV irradiation of
      solutions in mild aqueous acidic media of poly(caprolactone)-co-poly(ethylene
      glycol)-co-poly(caprolactone) diacrylate (PCL-PEG-PCL-DA) and chitosan. Hydrogels
      obtained were characterized using FT-IR, DSC, TGA and XPS. FT-IR, TGA and DSC
      revealed the semi-interpenetrating polymer network structure formed in the
      hydrogel. Though the water swelling degree of these chitosan-modified hydrogels
      was substantial in the range of 322-539%, it was found that fibroblasts could
      still attach, spread and grow on them; this is in contrast to the commonly
      investigated PEG-diacrylate hydrogel. The MTT assay demonstrated that cells could
      grow better on 3 or 6% chitosan-modified hydrogel than unmodified PCL-PEG-PCL-DA
      hydrogels or low-content (1%) chitosan-modified PCL-PEG-PCL-DA hydrogel.
      Increased chitosan content resulted in increased cell interaction and also
      decreased water swelling, both of which results in increased cell attachment and
      spread.

PMID- 15850287
TI  - Cation effect on thermal transition of iota-carrageenan: a photon transmission
      study.
AB  - Coil-to-double helix (c-h) and double helix-to-dimer (h-d) phase transitions of
      iota-carrageenan in various cation (CaCl2) solutions upon heating and cooling
      were studied using the photon transmission technique. Photon transmission
      intensity, Itr, was monitored against temperature to determine the (c-h) and (h
      d) transition temperatures (Tch and Thd) and activation energies (DeltaEch and
      DeltaEhd). An extra dimer-to-dimer (d-d) transition was observed during cooling
      at low temperature region. However, upon heating dimers directly decompose into
      double helices by making dimer-to-double helix (d-h) transition. Further heating
      results in double helix-to-coil (h-c) transition at high temperature region. Tdh
      and Thc temperatures and Delta Edh and DeltaEhc activation energies were
      determined. It was observed that Thc and Tch temperatures and DeltaEch and
      DeltaEhc activation energies were found to be strongly correlated to the CaCl2
      content in the system.

PMID- 15850288
TI  - In vitro thrombogenicity investigation of new water-dispersible polyurethane
      anionomers bearing carboxylate groups.
AB  - New segmented polyurethane (PU) anionomers based on hydroxytelechelic
      polybutadiene were synthesized via an aqueous dispersion process. Incorporation
      of carboxylic groups was achieved using thioacids of different length. Surface
      properties were investigated by mean of water absorption analysis and static
      contact-angle measurements using water, diiodomethane, formamide and ethylene
      glycol. Blood compatibility of the PUs was evaluated by in vitro adhesion assays
      using 111In-radiolabeled platelet-rich plasma and [125I]fibrinogen. Morphology of
      the adhered platelets was examined by scanning electron microscopy (SEM). Results
      were compared to two biomedical-grade PUs, namely Pellethane and Tecoflex.
      Insertion of carboxylic groups increased surface hydrophilicity and limited water
      uptake ( < 8% for an ion content of 5% by weight). Surface energy of all
      synthesized PUs was between 40 and 45 mJ/m2. Platelet adhesion and fibrinogen
      adsorption on the PU anionomer surfaces were affected as a function to the
      increase of graft length; thiopropionic was the most haemocompatible, followed by
      thiosuccinic and then thioglycolic acid. SEM analyses of all ionic PU samples
      exhibited low platelet adhesion to surfaces with no morphological modification.
      In conclusion, increased hydrophily, dynamic mobility and charge repulsion are
      synergistic key factors for enhanced haemocompatibility.

PMID- 15850289
TI  - Curcumin impregnation improves the mechanical properties and reduces the
      inflammatory response associated with poly(L-lactic acid) fiber.
AB  - We investigated poly(L-lactic acid) (PLLA) fibers and coils, simulating stents
      and the influence of impregnation with curcumin, a non-steroidal anti
      inflammatory drug, intended to reduce the pro-inflammatory property of these
      implants. Fibers obtained by melt extrusion of 137 kDa PLLA resin containing 10%
      curcumin (C-PLLA) exhibited a stable curcumin release rate for periods up to 36
      days. Curcumin increased the fiber tensile strength at break and decreased
      embrittlement vs. controls in 36 day 37 degrees C saline incubation. A mouse
      peritoneal phagocyte model was employed to test the anti-inflammatory properties
      of C-PLLA fibers in vitro. Myeloperoxidase and non-specific esterase activity
      assays were performed for adherent cells (polymorphonuclear leukocytes (PMN) and
      macrophages (MPhi), respectively). PMN and MPhi adhesion to C-PLLA fibers were
      significantly reduced compared to control PLLA fibers (2.6 +/- 0.91) x 10(5) vs.
      (5.6 +/- 0.67) x 10(5) PMN/cm2 and (3.9 +/- 0.23) x 10(3) vs. (9.1 +/- 0.7) x
      10(3) MPhi/cm2 (P < 0.05), respectively. In addition, superoxide release in the
      phagocyte pool contacting C-PLLA fibers was 97% less than that for PLLA controls.
      A fresh human whole blood recirculation system was employed to analyze cell
      adhesion under flow conditions, employing scanning electron microscopy (SEM).
      Reduced adhesion of cells on C-PLLA fiber coils vs. controls was observed. These
      in vitro studies demonstrate that bulk curcumin impregnation can reduce the
      inflammatory response to bioresorbable PLLA fibers, whilst improving mechanical
      properties, thereby suggesting curcumin loading may benefit PLLA-based implants.

PMID- 15850290
TI  - Poly(ethylene oxide)-b-poly(N-isopropylacrylamide) nanoparticles with cross
      linked cores as drug carriers.
AB  - Micelle-like nanoparticles that could be used as drug-delivery carriers were
      developed. The unique feature of these nanoparticles was that the core of
      poly(ethylene oxide)-b-poly(N-isopropylacrylamide) (PEO-b-PNIPAAm) micelle was
      lightly cross-linked with a biodegradable cross-linker, N,N
      bis(acryloyl)cystamine (BAC). The nanoparticles were characterized by dynamic
      light scattering and fluorescence measurements. When the BAC content ranged from
      0.75 wt% to 0.2 wt% of the mass of NIPAAm, the diameters of the nanoparticles
      were less than 150 nm. The anti-cancer drug doxorubicin (Dox) and 1,6-diphenyl
      1,3,5-hexatriene (DPH) were used as fluorescent probes to study the
      hydrophobicity of the cores of the nanoparticles; the results showed that the
      cores of the nanoparticles were hydrophobic enough to sequester Dox and DPH. The
      nanoparticles with 0.5 wt% BAC stored at room temperature were stable up to 2
      weeks, even at dilute concentrations. The degradation of BAC by reducing agent
      beta-mercaptoethanol was investigated, and the nanoparticles were not detectable
      14 days after adding beta-mercaptoethanol.

PMID- 15850291
TI  - Interaction of poly(styrene sulfonic acid) with the alternative pathway of the
      serum complement system.
AB  - Bioartificial pancreas, in which the islets of Langerhans are enclosed in
      artificial membrane to be protected from the host immune system, is expected to
      be a promising medical device to treat patients who suffer from insulin-dependent
      diabetes. Our strategy for preparation of a bioartificial pancreas involves
      utilizing a membrane including polymeric materials that can inhibit the
      complement reaction. In this study, we examined the effects of poly(styrene
      sulfonic acid) (PSSa) on the alternative pathway of the serum complement system
      to identify the mechanism(s) involved. PSSa was dissolved in pooled normal human
      serum (NHS), and the mixtures were incubated at 37 degrees C for 30 min.
      Complement activities in sera were determined by hemolytic assays. Amounts of
      complement activation products released were determined by ELISA. Interactions of
      PSSa with complement components and fragments were examined with electrophoresis
      and immunoblotting. From these examinations, it appeared that the manner of PSSa
      effects on the alternative pathway (AP) highly depends on its concentration. PSSa
      seemingly acted as an activator when its concentration was 0.005 g/dl to 0.05
      g/dl, while it acted as an inhibitor when its concentration was more than 0.1
      g/dl. In terms of activation or inhibition of the AP, forming complex of PSSa
      with factor H induced activation, and that with factor D induced inhibition.

PMID- 15850292
TI  - Molecularly imprinted bioartificial membranes for the selective recognition of
      biological molecules. Part 2: release of components and thermal analysis.
AB  - Molecularly imprinted membranes imprinted for a large-molecular-weight protein
      were realised using a blend of natural and synthetic polymers. Bioartificial
      membranes of synthetic (poly(ethylene-co-vinyl alcohol)-EVAL, Clarene) and
      biological (Dextran) polymers, molecularly imprinted with alpha-amylase as the
      template, were prepared and investigated. Dimethyl sulfoxide (DMSO) solutions of
      the alpha-amylase template, Clarene and Dextran were mixed under stirring in the
      desired proportions and dipped in DMSO (solvent)/water (non solvent) mixture, to
      obtain the phase separation. The release of Clarene, Dextran and alpha-amylase in
      the inversion baths was quantified by spectrophotometric methods and final
      composition of membranes was established. To study the interactions between the
      polymer components and between polymeric materials and the template, differential
      scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were carried out.
      Results indicated that stable and continuous bioartificial membranes of Clarene
      and Dextran can be obtained, whereby calorimetric analysis suggested the presence
      of high interaction between alpha-amylase and the Clarene component.

PMID- 15850293
TI  - [Tissue reaction after injection of polyvinylpyrrolidone (PVP) preparation into
      knee joint. Experiment].
AB  - Internally netted miscogelatinated preparation on the basis of
      polyvinylpyrrolidone PVP desioned for viscosuplementation of joint fluid was
      worked out. Netted structure of microgel grains presents larger resistance to the
      degrading action of free radicals than analogical linear polymer chains.
      Application of zoogeous preparations of hyaluronic acid results in short-term
      effects of their usage in evoking reaction foreign protein. Replenishment of
      joint fluid with preparation with higher biostability from biocompatible
      synthetic polymer-polyvinylpyrrolidone could improve the function of synovial
      through restoration of its proper viscosity and protection of the joint for a
      longer period of time. The aim of the experiment was determination of
      bioresistance and reaction of microgel PVP on the tissues of synovial joint. The
      tests were carried out on 10 white New Zealand rabbits after injection PVP into
      the knee joint for 3, 7, 14 and 30 days and submitted to macroscopic and
      histological evaluation. The results of tests were compared with the data
      obtained after injection of normal saline. Macroscopically, there were no changes
      in the limits of articular capsule and cartilage; there was only slight and
      enlargement of synovial membrane in the first 7 days after PVP injection. In
      histological tests it was observed that reaction in the knee joint after PVP
      injection was characterised it single inflammatory chains without essential
      participation of neutrophils observed only in synovial membrane and limited to
      places were tested preparation was seen. Microgel PVP was present in diverticula
      of synovial membrane to 30th day after injection.

PMID- 15850294
TI  - [Investigation of local reaction of muscular tissue after injection of
      polyvinylpyrrolidone preparation].
AB  - Natural preparations for replenishing of hyaluronic acid of zoogenous origin used
      till now, are characterized with quit low biocompatibility and also too short
      effect of their action. Recently worked out synthetic polyvinylpyrrolidone
      preparation PVP, contains modification constituting internally netting of
      microgels to improve polymer bioresistance. The introduce modification can,
      however influence PVP biocompatibility after deposition into tissues of the
      living organism. The aim of research was evaluation of the local reaction of
      muscular tissue after PVP infection. The results of research concerned a control
      group where normal saline was used for infections. The research was carried out
      on 18 Wistar rats and included macroscopic and histologic observations made in
      the 3rd, 5th, 7th, 14th and 30th day after PVP injection into thigh muscle. The
      local reaction of muscular tissue was macroscopically characterized with
      inflammatory reaction till the 7th day after PVP injection, in later terms the
      observed changes disappeared. Microscopic research showed that PVP till the 7th
      day after PVP injection caused rather strong diffuse non-specific inflammatory
      process, yet without essential participation of neutrophils leading to producing
      of loose intra-muscular. Connective tissue in a later term. The carried out tests
      showed presence of PVP in muscular tissue till the 30th day after injection.

PMID- 15850295
TI  - Carbopols as factors buffering triethanolamine interacting with artificial skin
      sebum.
AB  - Triethanolamine is an ethanolamine applied as counter-ion for fatty acid soaps.
      Interaction between triethanolamine and free fatty acids is suggested to be
      useful for cleansing sebaceous follicles in acne prevention. Considering
      relatively high pH of aqueous triethanolamine solutions we investigated influence
      of different concentrations of anionic polymers--Carbopol 934P, Carbopol 974P and
      Carbopol 980 on pH, rheological behavior and, most of them, intensity of
      triethanolamine interaction with artificial skin sebum components.
      Triethanolamine buffered using Carbopols influenced artificial skin sebum.
      Intensity of this interaction was measured applying specific optical method.
      Penetration of triethanolamine into artificial sebum and its uplift induced by
      above mentioned interaction were measured. Respective penetration rates and
      uplift rates were calculated. We found significant differences between Carbopols.
      The values of the penetration rates amounted 2.94 x 10(-04) h(-1) to 4.12 x 10(
      03) h(-1), whereas rates for the uplift process were from 1.97 x 10(-04) h(-1) to
      3.28 x 10(-03) h(-1). The value of pH is reduced from 10.06 for pure 0.1 M
      aqueous triethanolamine solution to 7.67 with the increase of polymer to
      triethanolamine molar ratio in the preparations. It is considered that
      triethanolamin buffered with acrylic acid polymers--Carbopols could influence
      cleansing of pilosebaceous unit follicles and contribute to acne prevention.

PMID- 15850296
TI  - Equilibrium solubilization of diclofenac by aqueous solutions of the products of
      lanolin oxyethylenation.
AB  - Systematic research has been conducted on the products of catalytic
      oxyethylenation of lanolin. The level of hydrophilic-lipophilic balance HLB and
      the amount of oxyethylene segments nTE in homologous series of products were
      determined by means of the 1HNMR method. Viscosity and spectrophotometry
      measurements were used to determine solubilization indices n/s/, the micellar
      partition coefficient K(m)w, and the solubility quotient i25(r) of diclofenac in
      aqueous solutions of surfactants. The determination of basic viscosity values
      enabled identification of the solubilization site of diclofenac molecules. For
      the purpose of application, the relationship between the amount of oxyethylene
      segments nTE and K(m)w of diclofenac determined in an equilibrium system was
      defined.

PMID- 15850297
TI  - Nonlinear Kedem-Katchalsky model equations of the volume flux of homogeneous non
      electrolyte solutions in double-membrane system.
AB  - In the paper the nonlinear Kedem-Katchalsky model equations of the volume flux in
      a double-membrane system are presented. The starting point are the classic Kedem
      Katchalsky equations. The model, which basis is the equation alpha(Jv)2 + betaJv 
      gamma = 0,, describes the stationary volume transport in the double-membrane
      system. The equations are essential in order to calculate the volume flux value
      (Jv) in the dependence on stimuli (i.e. the pressure difference (deltaP) and
      solutions concentrations (Cl, Cr)), and on the membranes parameters (Lp, omega,
      sigma). In the paper, research were carried out upon the influence of the
      pressure difference (deltaP) and solutions concentrations (Cl, Cr) on the volume
      flux value (Jv).

PMID- 15850298
TI  - The treatment of subclavian artery compression with the use of ringed
      polytetrafluoroethylene vascular prostheses.
AB  - In this paper the treatment of arterial complications of the Thoracic Outlet
      Syndrome (TOS) is presented. The investigation of 14 patients treated in the
      Department of Vascular, General and Transplantological Surgery of the Wroclaw
      Medical University for arterial complications of the TOS (as upper limb ischemia
      and/or the subclavian artery aneurysm in 14 patients) was performed. In case of
      complications associated with compression of the subclavian artery the operation
      consisted of resection of the first rib and accessory osseous and muscular
      pathological elements using supraclavicular and/or infraclavicular approach with
      implantation of externally supported ringed vascular polytetrafluoroethylene
      bypass (PTFE) were performed. The therapy results were estimated with use of The
      Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire of American
      Academy of Orthopedic Surgeons. RESULTS: In case of upper limb ischemia the
      improvement of blood flow was obtained after the subclavian-brachial bypass
      implantation (5 patients). In this group the DASH score showed return to full
      activity. In case of subclavian artery aneurysm surgery (9 patients) the DASH
      scale revealed worsening of limb function in 4 patients during follow-up period.
      The optimal therapy of vascular complications is the multimodal treatment
      (reconstructive vascular procedure with decompressive surgery). The decompression
      of neurovascular bundle in vascular TOS should include the first rib resection in
      each case.

PMID- 15850299
TI  - [Treating chronic pain in Spain today].

PMID- 15850300
TI  - [Pain in the hospital: from prevalence to quality standards].
AB  - OBJECTIVES: Pain diminishes the quality of life of patients and a high prevalence
      of pain calls into question the quality of health care being delivered. The
      present study analyzes the prevalence of pain in one hospital, by departments and
      by therapeutic approach used. PATIENTS AND METHODS: This cross-sectional study
      was carried out in a representative sample of 309 patients admitted to a tertiary
      care hospital. Information was gathered by patient interviews and by reviewing
      hospital records for personal characteristics, clinical situation, pain
      characteristics and analgesic treatment. RESULTS: The prevalence of pain was
      54.7% overall. The prevalence of pain eligible for treatment (intensity >2 on a
      visual analog scale) was 43.5%. The prevalence of pain that was moderate to
      intense (>3) was 34.7%. No analgesia was prescribed for 18.7% of the patients
      eligible, and analgesia was effective for 47.3%. Analgesia was provided on demand
      (63.2%) in most clinic protocols, usually with nonsteroidal antiinflammatory
      drugs, acetaminophen, opioids and special techniques, administered in combination
      to half the patients. The prevalence and intensity of pain and the prescription
      protocols varied from one hospital department to another. Analgesic treatment was
      adequate for 67.1% of the patients. CONCLUSIONS: The results suggest that the
      prevalence of pain in the hospital is high and that it is possible to improve
      quality of clinical approach, in agreement with studies that have been appearing
      since the 1980s. The persistence of the problem of pain in health care centers
      requires action on all levels of the health care system.

PMID- 15850301
TI  - [Descriptive analysis of chronic pain clinics operating in Spain in 2001].
AB  - OBJECTIVES: To describe the characteristics and care approaches to care of
      chronic pain clinics operating in Spain in 2001. DESIGN: Cross-sectional mail
      survey of pain clinics in Spain. SETTING: Chronic pain clinics in Spain.
      STATISTICAL ANALYSIS: Descriptive statistics of pain clinics responding to the
      questionnaire. RESULTS: Fifty-six of the 79 pain clinics (70.8%) responded; 57.1%
      were in public facilities, 55.4% were affiliated with medical schools, and 53.6%
      were interdisciplinary units. Both acute and chronic pain were treated by 72.4%
      of the respondents. Anesthesiology departments supervised 89.3% of the clinics.
      Only 57.1% had staff permanently assigned to the pain clinic. A mean 2194 (SD
      2041) visits by patients were received annually. The most commonly applied
      treatments were drugs, blocks, spinal techniques, and transcutaneous electrical
      nerve stimulation. Implantable systems were more frequently used in chronic pain
      clinics than in mixed pain clinics, and in university-affiliated clinics than in
      non-teaching facilities (P=0.03 in both comparisons). A psychological approach
      was used more often in interdisciplinary clinics than in units operated by staff
      from a single specialty (P<0.01). CONCLUSIONS: Chronic pain clinics were not
      evenly distributed throughout Spain. The number of patients treated at pain
      clinics was high. The various characteristics of pain clinics--such as funding
      source, interdisciplinarity, university affiliation, and specialization in
      chronic pain--a were factors that affected the use of certain treatments.

PMID- 15850302
TI  - [Exchanging and maintaining the airway in hyoid surgery: using a flexible
      exchanger during new surgical treatments for obstructive sleep apnea syndrome].
AB  - OBJECTIVE: To assess the level of intubation difficulty and anatomical changes
      after hyoid surgery. To evaluate the difficulty of switching from nasotracheal to
      orotracheal intubation after hyoid and palatopharyngeal surgery using an
      exchanger. MATERIAL AND METHODS: Prospective study enrolling 30 patients
      undergoing surgery for obstructive sleep apnea syndrome (OSAS) in 2 consecutive
      phases. Anatomical features suggesting risk of difficult intubation, anatomical
      changes caused by surgery, the incidence of failure to intubate upon first
      attempt during the first surgical session, and upon switching from nasal to oral
      intubation, and the time required to intubate were recorded. The rate of
      complications during and after surgery was also noted. RESULTS: The incidence of
      difficult intubation was 15% and no complications developed in the switch from
      nasotracheal to orotracheal intubation (100% success rate). CONCLUSION: New
      surgical treatments for the OSAS patient require new anesthetic maneuvers such as
      nasotracheal-orotracheal intubation exchange after hyoid surgery. The exchanger
      used in the present study offers a valid way to achieve airway management in this
      situation.

PMID- 15850303
TI  - [Caring for the victims of M-11].

PMID- 15850304
TI  - [Lumbar epidural anesthesia, 1931-1936: a second debut].
AB  - Fidel Pages Mirave (1886-1923) was a well-known Spanish military surgeon and
      among the first in the world to pioneer lumbar epidural anesthesia in 1920.
      Between 1931 and 1936, surgeons of various nationalities spread the use of lumbar
      epidural anesthesia worldwide. This second debut of metameric anesthesia has
      given us amusing anecdotes and stories of singular old- and new-world
      personalities who left a wealth of literature that deserves to be reviewed and
      valued. This review will use their original words and idiomatic expressions
      which, though archaic, have beauty and significance. Special emphasis is put on
      dates in comparisons. Because well-known names have been associated with lumbar
      epidural anesthesia, this review closes with the biographies of illustrious
      European and Latin American surgeons who played a major role in spreading the
      technique in the United States of America and other parts of the world.

PMID- 15850305
TI  - [False low oximetry reading caused by patent blue vital dye during breast
      surgery].
AB  - Patent blue vital (patent blue V; Laboratoire Guerbet, France) is used to
      identify the sentinel node during surgery for invasive breast cancer. Detecting
      the sentinel node that first drains the primary tumor reduces the need for total
      breast and wide axillary node removal, with the problems that such radical
      surgery involves. Like other dyes, patent blue V can interfere with accurate
      pulse oximeter reading, leading to underestimation of real values. We report the
      case of a 31-year-old woman who underwent lumpectomy and removal of the sentinel
      node. After intradermal injection of patent blue V dye into the left breast (100
      mg administered because the sentinel node was difficult to locate) a drop in
      peripheral oxyhemoglobin saturation from 99% to 93% was detected by the pulse
      oximeter. When arterial blood gas analysis showed normal values and other causes
      were ruled out, the diagnosis was false low oximetry reading due to patent blue V
      dye.

PMID- 15850306
TI  - [Aortic coarctation and postcoarctation mycotic aneurysm in a woman 20 weeks
      pregnant: anesthetic management].
AB  - A 28-year-old woman, 20 weeks pregnant, was diagnosed with aortic coarctation and
      postcoarctation mycotic aneurysm. After anesthetic induction, blood pressure was
      monitored in the radial artery of the right arm and the femoral artery of the
      right leg for two purposes: to verify hemodynamic stability as required in this
      type of operation and to determine the pressure gradient between the upper and
      lower limbs, which was approximately 40 mm Hg. To prevent spinal cord ischemia,
      an intradural catheter was inserted into the fourth and fifth lumbar space for
      spinal fluid drainage. A double lumen tube was used for intubation so that the
      left lung could be blocked, and a centrifugal pump was used instead of
      extracorporeal circulation. The aneurysm was resected through a left thoracotomy
      and an aortic prosthesis was placed. Satisfactory outcome was indicated by
      resolution of the pressure gradient, and fetal viability was verified by
      ultrasound. The mother suffered no neurological complications and the pregnancy
      continued to term uneventfully. We review the anesthetic procedure to follow in
      such cases.

PMID- 15850307
TI  - [Criss-cross heart: anesthetic considerations for total cavopulmonary shunt
      (Fontan procedure)].
AB  - We report the anesthetic technique used for interatrial septal defect a 2-year
      old girl weighing 11 Kg who presented with crossed atrioventricular connection
      (criss-cross heart), transposition of the great vessels, interatrial and
      interventricular septal defects, and subpulmonary and pulmonary valve stenoses.
      The patient was proposed for total cavopulmonary anastomosis with basal arterial
      oxygen saturation (SapO2) at 65%. Anesthesia was induced with inhaled agents and
      after intubation, hyperventilation was induced to achieve an end-tidal carbon
      dioxide pressure around 27 mm Hg. General anesthesia was provided in combination
      with spinal infusion of morphine chloride (100 microg Kg(-1)) for pain control. A
      Fontan procedure was carried out uneventfully with cardiopulmonary bypass.
      Milrinone was used at the extracorporeal circuit pump outlet. The patient was
      transferred to the pediatric intensive care unit where she was extubated without
      complications 90 minutes after admission. Anesthetic management is based on
      maintaining adequate preloading doses by administering volume, inhaled and/or
      intravenous agents, or use of vasoconstrictors and adjustment of ventilator
      parameters to modify pulmonary or systemic vascular resistance. We were able to
      maintain normal arterial pressure in our patient and provide adequate preloading
      through hyperventilation to reduce pulmonary vascular resistance.

PMID- 15850308
TI  - [Continuous sterno-cleidomastoid block and mid-humeral block for anesthesia of a
      shoulder and contralateral forearm fracture].

PMID- 15850309
TI  - [Pneumothorax due to a pulmonary fistula after nephrectomy].

PMID- 15850310
TI  - [Rhabdomyolysis after succinylcholine administration].

PMID- 15850311
TI  - [Vasopressin and terlipressin in anesthesia and postoperative recovery care:
      limits on use in Spain].

PMID- 15850312
TI  - [The most appropriate statistical test for comparing two assessment instruments].

PMID- 15850313
TI  - [Concepts of brain death and organ donation: the Jewish point of view].

PMID- 15850314
TI  - [Second meeting of the Critical Care Section of the Sociedad Espanola de
      Anestesiologia y Reanimacion].

PMID- 15850315
TI  - [Skin lesions caused by bacterial endocarditis].

PMID- 15850316
TI  - [Percutaneous and surgical revascularization in acute coronary syndromes without
      persistent ST segment elevation. One-year outcome of 361 patients assigned to
      early invasive strategy].
AB  - BACKGROUND: Percutaneous coronary interventions (PCI) and coronary artery bypass
      grafting (CABG) are well established revascularization methods in stable coronary
      artery disease and in acute coronary syndromes (ACS) as well. METHODS: We
      analyzed 361 patients hospitalized with clinical diagnosis of ACS without
      persistent ST segment elevation. Patients had an episode of rest angina in the
      previous 24 hours and had to fulfil at least one of the criteria: 1. ST segment
      depression (>0.5 mm), 2. transient ST segment elevation or T-wave inversion (> 1
      mm), 3. positive serum cardiac markers. We aimed at assessing the frequency of
      adverse events (death, myocardial infarction, repeat revascularization unstable
      angina, cardiovascular hospitalization) during follow-up and determining the
      predictors of 12-month mortality. RESULTS: In the analyzed group 284 patients
      (78.7%) underwent PCI and 77 patients (21.3%) were assigned to CABG. Overall
      mortality in the PCI group and in the CABG group was 3.5% and 9.1% respectively
      (p=0.04). In-hospital mortality rate was higher in the CABG group (7.8% vs. 1.8%
      p<0.02). After discharge mortality rate was 1.8% in the PCI and 1.4% in the CABG
      group (NS). The rate of MI during follow-up was similar in both groups. Fewer
      CABG patients had episodes of unstable angina, MI, repeat revascularization and
      cardiovascular hospitalisation. Independent predictors of death in the PCI group
      were: post-procedure recurrent angina (OR 2.40; 95%CI 1.20-4.19; p=0.03) and
      heart failure (OR 4.75; 95%CI 1.80-12.70; p=0.01), while in the CABG group these
      predictors were: inability to determine culprit vessel (OR 4,29; 95%CI 2.20-15.6;
      p=0.02) and heart failure (OR 7.70; 95%CI 3.74-21.49; p=0.05). CONCLUSIONS: We
      observed a higher overall mortality rate at one year in CABG patients, whereas
      PCI patients had a higher rate of unstable angina, repeat revascularization and
      cardiovascular hospitalization during 12-month follow-up.

PMID- 15850317
TI  - [Safety and efficacy of dalteparin administration for elective percutaneous
      interventions in patients pre-treated with aspirin and ticlopidine].
AB  - BACKGROUND: Prospective, randomized, double-blind study (POLENOX) proved that
      administration of low molecular weight heparin (LMWH)--enoxaparin for elective
      percutaneous coronary interventions (PCI) is as safe and as effective like
      unfractionated heparin (UFH). The aim of the present study was to determine
      safety and efficacy of the other LMWH--dalteparin for elective PCI. METHODS: 100
      patients planned for elective PCI were enrolled to the study. PCI were performed
      after i.v. dalteparin administration; 120 U/kg (up to 10 000 U). Importantly, all
      patients were pretreated with aspirin (75-325 mg per day) and ticlopidine (250 mg
      bid) prior to the procedure. During hospitalization rate of ischemic cardiac
      events and haemorrhagic complications were assessed. Serial CK and CK-MB were
      obtained 0, 8, 16, 24 hours after PCI. The results were compared with data from
      POLENOX study. Group 1 was treated with dalteparin, group 2 with UFH and group 3
      with enoxaparin. RESULTS: Rate of death, myocardial infarction (CK-MB elevation >
      x 5 normal level) and repeated revascularization in groups was similar. In group
      1 (0%; 2%; 1%) in group 2 (0.5%; 2%; 0%) in group 3 (0%, 2%, 0%) respectively. In
      group 1 CPK elevation (> 3 x normal) after PCI was more frequent (9%) in
      comparison with group 2 (3.5%) and group 3 (5%), but without statistical
      significance (p=0.14). Major bleeding complications were not observed in treated
      groups. Minor bleeding complications were more frequent in group 1 (9%) and 3
      (8.5%) than in group 2 (2%), p< 0.001. CONCLUSIONS: The use of dalteparin during
      PCI in patients with aspirin and ticlopidine pre-treatment is safe. However, more
      frequent benign local bleeding complications and mild CK-MB elevations may be
      expected.

PMID- 15850318
TI  - [Carotid artery stenting with different cerebral protection systems].
AB  - Carotid angioplasty with stent implantation (CAS) has become an alternative for
      carotid endarterectomy in treatment of carotid arteries atherosclerosis due to
      low procedural injury and comparable procedural risk. Wide application of
      cerebral protection devices decreased the procedural risk. The aim of the study
      was to estimate the procedural safety of CAS procedures with application of
      different cerebral protection systems. CAS procedures were performed in 48
      patients. One procedure was unsuccessful, in this patient stroke occurred. Distal
      occlusion balloon system was used in 5 patients, proximal occlusion balloons for
      common carotid artery was used in 21 pts and filter systems in 22 pts. During 6
      months follow-up, we observed no death nor stroke (40 pts). In one patient we
      revealed TIA. Moreover we found restenosis in one patient 6 months after CAS
      (total occlusion). In our experience CAS procedures were safe and incidence of
      major cerebro-vascular complications comparable to other centers.

PMID- 15850319
TI  - [Oxidative DNA damage in mothers of children with isolated orofacial clefts].
AB  - Recently, there is increasing evidence suggesting that oxidative stress may
      contribute to birth defects. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is considered
      to be a sensitive biomarker of oxidative DNA damage. It would seem important to
      establish whether levels of 8-OHdG and antioxidants are different in mothers of
      children with orofacial clefts comparing to women who gave birth to healthy
      children. The present study was carried out to investigate this point. Total
      plasma antioxidant status (TAS), serum 8-OHdG, plasma alpha-tocopherol and
      retinol were determined in 27 healthy mothers of children with isolated orofacial
      clefts (cleft lip - 11, cleft lip and palate - 9, cleft palate - 7; mean age -
      26.6+/-3.5 years; mean time after delivery - 6.5+/-8.4 months) and 14 control
      mothers of children without birth defect (mean age - 26.4+/-3.0 years, mean time
      after delivery - 5.7+/-5.8 months). 8-OHdG concentrations were significantly
      increased in mothers of children with clefts compared to controls (median - 4.7
      ng/mL; range: 0.5-8.6 ng/mL vs. median 1.9 ng/mL; range: 0.1-3.2 ng/ mL; p<0.001
      in Wilcoxon test). TAS (median - 1.03 micromol/L; range 0.87 - 1.26 micromol/L
      vs. median - 1.13 micromol/L; range: 1.03- 1.26 micromol/L; p<0,05) and alpha
      tocopherol level (median - 15.8 micromol/L; range: 11.3-26.8 micromol/L vs.
      median - 20.6 micromol/L; range: 13.8-26.5 micromol/L; p<0,05) were significantly
      reduced in mothers of affected children. There were no differences in vitamin A
      levels between the study group and controls. The ratio of alpha-tocopherol to
      plasma total cholesterol was lower in women who gave birth to children with
      clefts compared to controls (median - 3.16 micromol/mmol vs. median - 3.7
      micromol/ mmol; p>0.05). No correlation was found between TAS, the vitamins and 8
      OHdG. We conclude that depletion of antioxidant systems as well as increased free
      radical generation are likely to be involved in the pathophysiology of orofacial
      clefts in humans. The results indicate the necessity of futher studies to
      establish whether peri-conceptional antioxidant supplementation will prevent
      these serious defects.

PMID- 15850320
TI  - [Assessment of soluble E selectin levels in patients with Graves' disease and
      thyroid orbitopathy].
AB  - The aim of this study is to evaluate serum concentrations of sELAM-1 in patients
      with Graves' orbitopathy (GO). We studied levels of soluble form of E selectin -1
      in patients with euthyroid progressive GO (group I) and euthyroid stable GO
      (group II), hyperthyroid Graves' disease (GD) without GO (group III) and in
      healthy controls (group IV). sELAM-1 levels were measured by ELISA method. The
      highest serum levels of sELAM-1 were found in group III. Mean sELAM-1
      concentrations in patients with progressive and stable GO were slightly lower
      than those in group III patients. The sELAM-1 serum concentrations in group I and
      II were comparable, nearly the same despite the different clinical picture of the
      disease in both groups. Mean serum concentrations of sELAM-1 decreased
      significantly during treatment of progressive GO, parallel to the improvement of
      the eye changes. In conclusion, sELAM-1 concentrations do not reflect the degree
      of GO activity. A significant decrease in sELAM-1 concentrations are associated
      with the efficient outcome of treatment. Increased sELAM-1 levels seem to result
      form both GO and GD.

PMID- 15850321
TI  - [Concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1) in
      patients witt Graves' disease and thyroid associated orbitopathy].
AB  - The aim of this study is to evaluate serum concentrations of sVCAM-1 in patients
      with Graves' disease (GD) and thyroid associated orbitopathy (TAO). We measured
      serum sVCAM-1 levels in initially hyperthyroid GD patients without TAO, in
      patients with progressive and stable orbitopathy in euthyroid stage of GD and
      healthy controls. The highest serum concentrations of sVCAM-1 were observed in
      patients with hyperthyroid GD. In patients with euthyroid GD and progressive TAO,
      sVCAM-1 levels were slightly decreased than those in the group of patients with
      hyperthyroid GD and markedly elevated in comparison to the group of patients with
      stable TAO. In patients with hyperthyroid GD, sVCAM-1 concentrations dropped
      significantly after they had become euthyroid , but were still higher than those
      observed in group of patients with stable TAO and healthy people. Serum levels of
      sVCAM-1 in early stage of the progressive TAO (<6 m-ths) were higher than those
      in late stage of the disease (>6 m-ths), despite lower orbitopathy index (OI)
      found in early stage of the orbitopathy (<6 m-ths). In conclusion, both
      hyperhyroidism and TAO may contribute to elevated levels of sVCAM-1. A
      significant decrease in sVCAM-1 levels in initially hyperthyroid GD patients is
      associated with euthyroid stage of the disease. Concentrations of sVCAM-1 seem to
      correlate with the activity, not severity of progressive TAO.

PMID- 15850322
TI  - [Analytical problems of iodine defficiency examination in Polish Nation-wide
      deficit control program].
AB  - The environmental iodine deficiency has been a serious problem in the Polish
      health care system for many years. In many European countries the prevention of
      iodine deficiency-related health deficits in population scale is based on edible
      salt supplementation with KI. In the decade of the 80-ties the iodine
      supplementation program in Poland was stopped, which has caused a subsequent
      increase in prevalence of goiter and iodine deficiency-related hypothyreosis.
      These diseases were observed in many regions of Poland, including the areas
      beyond regions of formerly known iodine deficiency endemias. In order to control
      the whole Polish population, iodine consumption deficit in1991 the "Polish
      Program of Iodine Deficiency Control and Prevention of Iodine Deficiency-related
      Disorders" has been established in the year 1991. In 1992--1996 a common iodine
      supplementation of salt used for general consumption was 20 mg KI/kg of NaCl, and
      in 1997 the mandatory supplementation of salt was 30 (+10) per kg of salt which
      has been introduced for the whole country. This paper reports the results of
      iodine excretion assays in school children 6-12 years old, in the years 1993--94,
      1996--97 and 1999--2002 respectively. The obtained collections of iodine urine
      concentrations have shown distributions with a remarkable rightward skewness.
      Normalization of distributions required logarythmic transformation. The quartile
      values obtained for data collections from years 1992--94, 1996--97 and 1999--2002
      have shown that in 5-7 years of iodine deficiency prevention program yielded
      increase in iodine excretion in morning urine samples by about 37.8 microg, while
      the iodine excretion median values increased from 63.5 mg/L in years 1992--1994
      to 94.0 mg/L in years 1999--2001, respectively. The lower limits of iodine
      excretion ranges calculated as the mean value minus 2SD of transformed data for
      the years 1992--1994 amounted to: 7.74 mg/L and for the years 1999--2001 amounted
      to 14.1 microg/l, respectively. Assessing percent of children obtaining low
      iodine suplementation then recommended (below 50 mg/L in urine sample) amounted
      to 35.8% in years 1992--1994 and 15.4% in years 1999--2001 respectively.

PMID- 15850323
TI  - [The occurrence of food allergy and bacteria allergy in chiidren with tonsilar
      hypertrophy].
AB  - The diagnosis of food allergy is difficult because it is a multifaceted problem
      and is incompletely understood. Both upper and lower respiratory tracts can be
      affected by food allergy. The importance of bacterial allergy of the upper
      respiratory tract is however one of the most controversial problems in
      allergology. The palatine tonsils play an important role in immunologic
      surveillance and resistance to infection in the upper aerodigestive tract. The
      role of enlarged adenoids and tonsils in upper airway obstruction has become well
      established earlier, thus, adenoidectomy with, or without, tonsillectomy is one
      of the most commonly performed surgical procedures in the paediatric population.
      Research done in respect to Waldeyer's ring on people dealing at the same time
      with allergy, is seldom the subject of dissertation in Polish as well as world
      wide medical literature. To examine the influence of food and bacterial allergy
      on the tonsilar hypertrophy (TH) we studied 136 children ages 3 to 7 years, who
      had TH. On the basis of allergic and immunological examinations, in 28.6% food
      allergy was confirmed as the main cause of the complaints. We conclude that large
      tonsillar tissues sometimes with upper airway obstruction may by caused or
      aggravated by food allergies, therefore, early prevention of exposure to them may
      help reduce occurence of TH.

PMID- 15850324
TI  - [Feelings and emotions in women treated for infertility].
AB  - The aim of this study was an assessment of women's moods and emotions during
      infertil-ity treatment. Sixty married women diagnosed and treated for primary
      infertility at Division of Infertility and Reproductive Endocrinology Department
      of Gynecology and Obstetrics University of Poznan Medical Sciences from January
      to April 2003 were included in this study. The average age of women was 28.5
      years. Control group consisted of 30 female students at similar age, single, not
      planning pregnancy in the nearest future. Depression was assessed using Beck
      scale. The special questionnaire was made to evaluate women's different
      psychological features connected with infertility. The interviews had a personal
      character and every question was filled in the questionnaire by the investigator.
      The first reaction most patients experienced when they found out about
      infertility was: 1) astonishment 2) sadness 3) anger, and similar was the opinion
      from the control group. Both the patients and the control group consider that
      having a baby is: 1) goal of their lives 2) sense of marriage 3) providing a
      woman with a sense of fulfillment. More than 25% of both groups of women think
      that infertility is the most important problem for their couples. Economic
      difficulties seem to be the biggest problem for patients during their treatment
      of infertility. What is very interesting patients average Beck scale depression
      score was significantly higher that of control respondents (8,6 points for
      patients and 4,4 for control group).

PMID- 15850325
TI  - [Neutrophil oxidative metabolism in children with chronic hepatitis C].
AB  - A growing number of data suggest the role of reactive oxygen species (ROS) in the
      pathogenesis of chronic type c hepatitis. Activated neutrophils, macrophages and
      Kupffer cells are basic sources of ROS in the course of the inflammatory process
      in the liver. The aim of the study was to assess the metabolism of neutrophil
      oxygen in children with chronic hepatitis C. MATERIAL AND METHODS: The study
      comprised 14 children with chronic hepatitis C (group 1), 4 children with
      positive serum anti-HCV antibodies and negative HCV RNA as well as normal ALT
      activity (group II) and 6 healthy children 9 (group III). Production of reactive
      oxygen species by neutrophils using the method of chemiluminescence (CL) with
      luminol (MLX Microtitier Plate Luminometr, Dynex, USA) was assessed. We estimated
      chemiluminescence response (CL max and CL total) of neutrophiles both
      unstimulated and stimulated by formyl-methionyl-leucyl-phenyloalanine (fMLP),
      opsonized zymosan (OZ), phorbol-myristate-acetate (PMA) without and after priming
      with tumor necrosis factor alpha (TNF-?) was estimated. RESULTS: CL max f MLP
      stimulated without preactivation was significantly lower in group I and II than
      in group III (p<0.04, p<0.06, respectively). CL max OZ stimulated was
      significantly higher in group I in comparison to group II (p<0.04) and it tended
      to be higher in group I than in group III. CL max PMA stimulated was lower in
      group I compared to group III (p<0.08). CL total fMLP stimulated was lower in
      group II (p<0.07) compared to group I and it tended to be lower in group I and II
      compared to group III. CL total OZ stimulated was significantly higher in group I
      than in group II (p<0.05) and group III (p<0.03). CL max and CL total OZ
      stimulated and preactivated with TNFalpha was significantly lower in group I
      compared to group III (p<0.02 and p<0.04, respectively). SUMMING UP: In the
      course of chronic hepatitis C in children, both neutrophil preactivation and
      inhibition of neutrophil release of reactive oxygen species, which occur as a
      result of different mechanisms, are observed.

PMID- 15850326
TI  - [Carbohydrate metabolism in children with chronic hepatitis C].
AB  - The importance of carbohydrate metabolism in the pathogenesis of chronic
      hepatitis C has been recognized in recent years. The aim of the study was to
      assess carbohydrate metabolism in children with chronic HCV-related hepatitis.
      MATERIAL AND METHODS: The study was comprised of 16 children with chronic
      hepatitis C and 16 healthy controls. In all the children anthropometric data and,
      after overnight fasting, serum levels of glucose and insulin were investigated
      and insulin resistance index HOMA IR was calculated. In the study group biopsy
      specimens were assessed. RESULTS: Macrovesicular steatosis in numerous
      hepatocytes was found in 3 children. Mean values of body mass, height, body mass
      index (BMI), levels of glucose, insulin and HOMA IR did not differ significantly
      between the two groups. We found correlation between serum levels of glucose and
      fibrosis (r=0.64, p<0.01) or staging (r= 0.7, p<0.004) in children with chronic
      hepatitis C. CONCLUSION: Neither obesity, which is recognized as a risk factor
      for diabetes mellitus and steatosis was found in children with HCV-related
      hepatitis. Correlation between serum levels of glucose and fibrosis or staging in
      children with chronic hepatitis C suggests the participation of carbohydrate
      metabolism in the pathogenesis of this disease and the risk, existing already in
      such young patients, of developing hepatic fibrosis with its consequences.

PMID- 15850327
TI  - [A role of endothelin 1 in the pathogenesis of thromboangiitis obliterans
      (initital news)].
AB  - BACKGROUND: [corrected] Etiology and pathogenesis of thromboangiitis obliterans,
      an uncommon disease, but connected with high risk of leg amputation, is still
      unknown. Genetic predisposition and inconvenient factors of environment,
      especially nicotine, could initiate an immunological process, which evokes
      endothelial dysfunction. In histological preparation inflammation and thrombus
      are observed. Endo-thelin-1 could affect these processes. It is a strong vasa
      constrictor and has a wide spectrum of biological activity, often opposed to
      effect of prostacycline analogs. The aim of study was a role of endothelin-1,
      antielastin antibodies and selectin P, L, E in the pathogenesis Buerger's disease
      and influence of alprostadil on these parameters. MATERIAL AND METHODS: We
      examined 10 patients with Buerger disease in the active phase, which were divided
      in two subgroups. Four persons with necrosis of toes were in the first subgroup,
      and six patients with rest pain but without trophic changes in the second
      subgroup. 13 healthy persons composed the control group. Index of antielastin
      antibodies, concentration of endotehlin-1, selectin P, L and E were measured in
      venous and arterial serum. These parameters by patients were determined twice:
      before and after 10-days treatment with alprostadil 20-40 microg per day.
      Concentration of endothelin-1, selectins and index antielastin antibodies were
      measured by enzyme-linked immuno-sorbent assay. RESULTS: We observe increase in
      endothelin-1 concentration by persons with necrosis of toes compared to patients
      without these changes (p=0.024) and to control (p=0.022). In the subgroup I index
      of antielastin antibodies IgA was higher than in control group (p=0.020). After
      alprostadil treatment endothelin-1 concentration, antielastin antibodies index
      was not statistically significant compared to results before treatment or control
      group. We observed correlation between concentration of endo-tehlin-1 before
      treatment and index of antielastin antibodies IgG (p=0.0475). We observed
      significant diffrance of concentration of selectin P, L and E compared to control
      (p=0.038). Especially we noticed higher concentration of selectin P (p=0.001)
      than in control group. The after treatment reduction of concentration was only
      for selectin L statistically significant (p=0.038). CONCLUSION: 1. Plasma
      endothelin-1 level play a role in the exacerbation of clinical symtpoms of
      thromboangiitis obliterans. 2. Endothelial injury is connected with increase in
      concentration of selectin P in patient's serum. 3. Alprostadil didn't influence
      on concentration of endothelin-1 in these patients.

PMID- 15850328
TI  - [Health-related quality of life in the elderly after coronary artery bypass
      grafting].
AB  - Despite of higher operative risk in the elderly, coronary artery bypass grafting
      (CABG) is more often performed in this age group to achieve the remission of the
      disease and to improve the quality of life. The aim of the study was to assess
      some subjective and objective health indices in the elderly two years after CABG
      (I group) in comparison to analogous group of older patients just waiting for
      CABG (II group). 109 patients aged 65 years and older, consecutively discharged
      from the Cardiac Surgery Department 2 years ago, were analyzed as well as 60
      patients currently waiting for such surgery. Both groups of patients did not
      differ with demographic features. The health related quality of life was measured
      with the EASYCare questionnaire and similar one of own construction supplemented
      with some items of the WHOQol-BREF scale. Two years after CABG, 100 patients were
      available for the study (six persons died and three persons refused). Response
      rate was 92%. Significant reduction of symptoms of the coronary artery disease
      were shown. The chest pain was declared in 18% in I group vs 70% in II group;
      palpitation in 23% in I group vs 38% in II group and effort angina in 38% in I
      group vs 65% in II group. The positive evaluation of the health status was
      declared significantly more often in the patients of I group in comparison to
      patients in II group. CABG caused positive change concerning health-related
      quality of life in the elderly two years after surgery.

PMID- 15850329
TI  - [Hand injuries in elderly patients].
AB  - We studied 1199 patients treated in II Department of Surgery in Cracow between
      1987 and 2000. In the studied group, 138 patients were aged over 60 years. In
      most cases the injury took place at home (43.68%) and more often than not they
      occurred during operating mechanical equipment (52.89%) among which circular saw
      predominated (35.51%). It was revealed that the hand injuries of senior patients
      were more severe compared with the other patients and the permanent post-injury
      disability was more intense. The elderly patients with multi-tissue hand injuries
      should be treated in specialist centers. It is also essential to start as soon as
      possible the therapeutic rehabilitation (even during surgical treatment). Only
      such proceedings enable better final results of treatment.

PMID- 15850330
TI  - [The health status of the long lived elderly in Cracow].
AB  - The main goal of the work was to assess the health status of the long-lived
      elderly living in the community of a large city. The research was done in the
      years 2000--2001. In order to make comparisons possible, considered was a
      randomized sample of Krakow's citizens in the age of 75-80 (258 people) and 90-95
      (172 people). The following tools were used in the research: MFAQ (Older
      Americans Resources and Services Multidimensional Functional Assessment
      Questionnaire) and commonly accepted scales: Abbreviated Mental Test, Geriatric
      Depression Scale and Activity of Daily Living Index. RESULTS: No significant
      differences in number of chronic diseases reported, in the number of drugs taken
      and in the level of self-reported depression between the long-lived elderly and
      people between the ages 75-80, were found. Nevertheless the long-lived elderly
      more often assess their health status as poor, report disability in vision and
      hearing, cognition disorders and lower ability to perform activities of daily
      living. The long-lived women have much worse health status than the long-lived
      men. CONCLUSIONS: The health-related quality of life of the long-lived elderly is
      much worse than the quality of life of the people 75-80 y.o. The long-lived women
      have worse health status than men over 90. The much worse self-reported health
      status of long-lived elderly seems to be not the result of the number of chronic
      diseases reported, but is mainly related to the lower level of ADL, more frequent
      vision and hearing disabilities and cognition disorders present at the age over
      90.

PMID- 15850331
TI  - [Clinical analysis and demographic characteristics of the sample of patients from
      the psychiatric outpatient clinic for chiidren and adolescents].
AB  - The article presents the demographic and clinical analysis of the sample of 679
      persons in age under 20 who were out-patients in the Clinic of Child and
      Adolescent Psychiatry in Cracow (Poland) during one year. The clinical analysis
      takes into account among others the structure of diagnoses set according to ICD
      10, the presence of additional diagnoses and risk factors, the way patients were
      referred to the out-patient units, and the sort of the care proposed. Most often
      syndromes from the section of emotional and behavioral disorders of childhood and
      adolescence (F90 - F98 in ICD-10) were recognised. On the level of separate
      disorders most popular in adolescents were anorexia nervosa (16%), adolescent
      depression (10%), acute psychoses (8%), and adjustment disorder (8%). In the
      discussion the results were referred to epidemiological community studies. It has
      been also noticed that the way symptoms of adolescence are understood is
      essential in psychiatric evaluation of adolescents.

PMID- 15850332
TI  - [Assessment of presence and degree of depression in elderly, chronic ill
      patients: application selected scales advantages and disadvantages of this method
      of diagnosis].
AB  - The aim of our study was to assess diagnostic worth of 3 popular scale of
      depression in the group of elderly, chronic ill patients, treated in internal
      hospitals. 3 scales were used: Hamilton Depression Rating Scale (HDRS) Beck
      Depression Inventory (BDI), Geriatric Depression Scale (GDS). Results were
      compared to assessment of presence and degree of depression according to ICD-10.
      The sample consisted of 30 elderly ill patients who were admitted in Internal
      Institute Medical University in Gdansk. There were 15 women and 15 men, the mean
      age: 72.8+/-7.02 years. We assessed agreement of diagnosis between 3 psychometric
      methods in comparison with results after standard psychiatric examination.
      Specifities of HDRS and BDI were low: 66%. Correlation coefficients between
      scales were high 0.74-0.87. But only compared to BDI and GDS there were no
      significant differences between distribution of patients in each group of
      depression intensity measured chi2 test. In case of HDRS there was significant
      difference which was an effect of false positive results. Our results showed
      small usefulness of HDRS in this group of patients. Scales of depression are
      useful in 2 important conditions: I. Scale should not replace full psychiatric
      examination. II. Proper scale for age and somatic state should be applied.

PMID- 15850333
TI  - [Parkinson's disease and depression: commorbidity, signs, etiology, clinical
      implications].
AB  - Depressive symptoms often occur in Parkinson' disease. They have negative
      influence for patients' quality of life. However, they are not sufficiently
      diagnosed nor correctly treated. Difficulties with the diagnosis could be a
      result of: partial confusion of symptoms of Parkinson's disease and depression
      and/or different clinical depressive symptoms, compared to "primary" affective
      disorder. Correlation between cognitive functions, Parkinson' disease and
      depression remains pretty unclear. Depression occurring during Parkinson's
      disease must be treated. Theoretically all kinds of treatment for depression can
      be applied. Nowadays, among antidepressive agents, SSRI's are preferred, mainly
      because of its good tolerance.

PMID- 15850335
TI  - [Gynecological endoscopy--laparoscopy].
AB  - The development of operative laparoscopy in gynecology and obstetrics has greatly
      increased in the past decade. The Authors attempt to show the most important
      applications of the laparoscopic procedures in the diagnostics and therapy of
      gynecological diseases.

PMID- 15850334
TI  - [Surgical treatment of Parkinson's disease].
AB  - Parkinson's disease (PD) is one of the most common neurodegenerative diseases.
      Its pathogenesis is based on diminution of neurons in substantia nigra, that
      under normal conditions acts as the source of dopamine in nigrostriatal circuit.
      The decline of dopamine concentration caused by death of dopaminergic neurons is
      responsible for the appearance of symptoms typical for the mentioned disease.
      Along with pharmacotherapy, with its most impressive success - that is delivery
      of the precursor of dopamine (L-DOPA) to the central nervous system--surgical
      methods are developed for treatment of PD. The basis of these approaches consist
      of "switching off" the nigrostriatal structures that are overactive due to lack
      of inhibiting action performed normally by dopamine. Stereotactic neurosurgery -
      enabling safe access to the region of basal ganglia, thalamus and subthalamic
      nucleus can be an important solution for many patients with the PD unresponding
      to pharmacological therapy. Depending on the procedure irreversible lesions or
      stimulation leading to reversible block can be done in order to restore
      physiological functional conditions within nigrostriatal circuit. The new,
      experimental method of curing PD is transplantaton of dopaminergic rich neurons
      from fetal mesencephalic tissue. Despite very promising results, this procedure
      is very controversial due to ethical problems concerning aspects of fetal graft
      acquisition. In the authors' point of view, the only chance for making the
      concept of neurotransplantation applicable is the use of neural stem cells that
      are able not only to renew dopaminergic neuron population, but also, thanks to
      gene therapy--introducing key substances (e.g. thyrosine hydroxylase, glial cell
      line-derived neurotrophic factor) and elimination the cause of parkinsonian
      disturbances.

PMID- 15850336
TI  - [Computerized fluorocolposcopy--the significance in evaluation and therapy of
      early cervical lesions].
AB  - Understanding of cervical cancer biology has made it was possible to determine
      intraepithelial lesions in the early stage of carcinogenesis.The aim of the study
      was to design the computer model of colour analysis of fluorocolposcopic
      pictures, based on biology evaluation of early epithelial cervical lesions. From
      the other hand increasing non-radical treatment efficacy by the precise
      visualisation of the biopsy place and borderlines of therapeutic tissue
      destruction, using digital model of colours analysis. All colours typical of
      Berthalanffy technique were characterised by 3D mathematical, digital model in
      the range of primary colours (R-red; G-green; B-blue) and Munsell System
      components (H-hue; S-saturation; l-intensity). Digital model of colour analysis
      of fluorocolposcopy images lets precise evaluations of early epithelial cervical
      lesions. Computerised fluorocolposcopy seems to be an examination with higher
      diagnostic accuracy (sensitivity - 97.8%, specificity - 99.8%, k rate - 0.93).
      Mathematical model of digital colour analysis also lets very precise
      visualisation of the biopsy place and borderlines of therapeutic tissue
      destruction.

PMID- 15850337
TI  - [Mass screening programs running in Podlaski region based on standards existing
      in European Union-- actual status and future perspectives].
AB  - High mortality rates caused by breast cancer and cervical cancer are still an
      actual and enormous problem in our country. Such unfavorable epidemiological
      situation lasts for many years, in spite of availability of diagnostic
      procedures, which permits secondary prevention of these diseases. Successes of
      mass screening programs conducted in several European Countries are the best
      proof for this statement. For the last years the number of mammography and
      cytology tests systematically have been been going up in our country,
      unfortunately without any effects on women's mortality rates. The question
      arises: what is the reason for that situation and if could it be useful to adopt
      European experiences into the Polish conditions? This could be done by
      appropriate staff training and increase of effectiveness of diagnostic and
      therapeutic procedures. One more core element of mass screening programs is
      logistic background--coordinating center ensuring good functioning of the
      screening program.

PMID- 15850338
TI  - [Hydrogen sulfide water balneum effect on erythrocyte superoxide dismutase
      activity in patients with rheumatoid arthritis--in vitro study].
AB  - The aim of the study was to investigate, in vitro, hydrogen sulphide water
      balneum effect on erythrocyte superoxide dismutase activity in patients with
      rheumatoid arthritis. Erythrocytes from 29 consecutive patients with rheumatoid
      arthritis (11 men, 18 women) aged 54 years were obtained. The control group
      comprised of 30 healthy subjects with a mean age of about 40 years. Patients with
      rheumatoid arthritis were subdivided into two groups: with active disease (18
      patients) and in remission (11 patients), and secondly into patients receiving
      (21 subjects) and not receiving (8 subjects) non-steroidal anti-inflammatory
      drugs. For erythrocyte superoxide dismutase activity evaluation, with method of
      Misra i Fridovich was used. Superoxide dismutase activity was assessed after 5,
      10, 15, and 20 minutes erythrocytes incubation with hydrogen sulphide water. The
      mean baseline erythrocyte superoxide dismutase activity (T0) was in rheumatoid
      arthritis patients 1589.95+/-208.41 U/gHb and was 1622.12+/-321+/-321.58 U/gHb in
      the control group (ns). After 5 and 10 minutes of incubation with hydrogen
      sulphide water T0-T5 i T5-T10 erythrocyte superoxide dismutase activity increased
      significantly (p<0.05) in rheumatoid arthritis patients. In rheumatoid arthritis
      patients erythrocyte superoxide dismutase activity was higher and increased
      significantly when compared with control group. It seems that hydrogen sulphide
      water balneum produces an antioxidant effect on erythrocyte status in patients
      with rheumatoid arthritis.

PMID- 15850339
TI  - [Isoprostanes--new possibility of the oxidative stress estimation].
AB  - Isoprostanes are new markers of the oxidative stress estimation. They are
      chemically stable prostaglandin isomers that are produced by free radical
      catalyzed peroxidation of polyunsaturated fatty acids, among other things
      arachidonic acid. Isoprostanes, in contrast to prostaglandins, are synthesized in
      cell membrane or in lipoproteins phospholipid, and are released into circulation
      by the action of phospholipases. Isoprostanes circulate in plasma, and are
      uptaken and metabolised by the tissues. Isoprostane metabolites and their non
      metabolised forms are excreted in urine. Isoprostanes, especially 8-iPF2alpha
      III, possess potent biological activity. They cause vasoconstriction, induce
      mitogenesis and may modulate platelet functions. Clinical data indicate an
      increased level of isoprostanes biosynthesis in certain diseases related to
      oxidative stress. These compounds have longer half life than other of lipid
      peroxides, and methods for measurement of isoprostanes are more sensitive and
      specific than methods for measurement of other peroxidation products.

PMID- 15850340
TI  - [Hypoxia involvement in erythropoiesis regulation--a new insight].
AB  - Oxygen, carried mainly by erythrocytes, plays a crucial role in human organisms-
      as the terminal electron acceptor enables mitochondria functioning and energy
      production. Oxygen excess may be a cause of the damage of basic structural
      organism components--proteins, lipids and nucleinic acids. Thus, from the
      biological point of view, regulation of oxygen supply with its detection
      mechanisms is a critical process. Erythrocyte content optima-lization, in means
      of "benefit-loss" is a compromise between the necessity of anaerobic metabolism
      transit (in case of too low erythrocyte count), excessive increase in blood
      viscosity and non-productive, increased red blood cell turn-over with increased
      erythrocyte level. It is in fact a process of adaptation to changeable
      environmental conditions, life style and possible pathological processes. The
      study is a review of knowledge on the oxygen sensor and its connection to
      erythropoiesis regulation.

PMID- 15850341
TI  - [Biochemical diagnostics in acute pancreatitis recognition and outcome
      predicition].
AB  - Acute pancreatitis (AP) is a common disease associated with an improper
      activation of pancreatic zymogens leading to autodigestion of the gland and if
      excessive--to multiple organ dysfunction. Acute necrotizing pancreatitis
      manifested by 20% of patients with acute pancreatitis is a life threatening
      disorder requiring subsequent management in intensive care unit. Unfortunately,
      none of biochemical tests presently used for laboratory assessment of acute
      pancreatitis at the early stage of the disease is able to estimate accurately:
      diagnosis, etiology and severity. At present, diagnosis of acute pancreatitis is
      based on evaluation of serum amylase and lipase activity due to easy availability
      and simplicity of these enzymatic tests. Low specificity of the mentioned enzymes
      resulted in studies concerning pancreatic isoamylase, elastase-1, chymotrypsine,
      procarboxy-peptidase B, trypsinogen-2 and immunoreactive trypsinogen usefulness
      in the laboratory diagnosis of AP. The prediction of severity in acute
      pancreatitis using multifactorial scoring systems is cumbersome especially due to
      their complexity. On the other hand the biochemical method of choice, estimation
      of serum C reactive protein, is useless in the early phase of disease.
      Unfortunately, the computed tomography--the most accurate method in severity
      assessing--is not always available. Recent studies have brought some progress in
      severity predicting, such as phospholipase A2, cellular immunity markers,
      cytokines, activation peptides of trypsinogen and carboxypeptidase B,
      procalcitonine, pancreatitis associated protein and serum amyloid A. All these
      newly introduced biochemical methods allow to look optimistically into the future
      of laboratory diagnostics of the acute pancreatitis believing that the problem of
      diagnosing and predicting the AP severity will be solved.

PMID- 15850342
TI  - [Current knowledge on diastolic heart failure].
AB  - Heart failure (HF) is still one of the most common causes of hospitalisation.
      Originally it was understood as systolic function impairment, but it is prooved
      that 40 to 50 percent of patients with clinical symptoms of HF have normal
      systolic function. These data lead to diagnosis of diastolic heart failure (DHF).
      The diastoly of the left ventricle consists of four stages: isovolumetric
      relaxation, early mitral inflow, slow mitral inflow and left atrium contraction.
      Authors have presented definition, epidemiology and basic pathophysiology of DHF.
      The categories of myocardial and non-myocardial pathogenic mechanisms have also
      been described. The clinical symptoms that allow to distinguish diastolic from
      systolic heart failure (SHF) have been pointed. The most common disorders that
      affect diastolic function like hypertension, coronary artery disease and diabetes
      have been described. Recent guidelines on therapy in diastolic heart failure have
      been also presented.

PMID- 15850343
TI  - [High density lipoproteins and atherosclerosis].
AB  - HDL lipoproteins play an essential protective role against development of
      atherosclerosis 2 they participate in reverse cholesterol transport, act as
      antioxidants and have antiinflammatory properties. Antioxidant properties of HDL
      are associated with enzymes such as paraoxonase, LCAT and apolipoproteins apo A
      1, apo A-2. HDLs antiinflammatory functions are associated with inhibition of
      expression of cellular adhesion molecules. Increase of low HDL-cholesterol
      concentration is now one of the main goals of treatment of lipid disorders for
      prevention of atherosclerosis and coronary artery disease. In this article we
      summarised the role of HDL in atherosclerosis development and influence of fish
      oils and antioxidant vitamins on lipids and lipoproteins fractions.

PMID- 15850344
TI  - [The role of peroxisome proliferator-activated receptor gamma in the pathogenesis
      of diabetes and atheromatosis].
AB  - The high risik of cardiovascular diseases in diabetes is connected with wide and
      premature atheromatosis. It is caused by systemic metabolic disorders like
      hyperglycaemia, insulin resistance, dyslipidaemia, endothelium dysfunction. This
      review will discuss the role of peroxisome proliferator-activated receptor gamma
      (PPARgamma) in the pathogenesis diabetes and atheromatosous injury of vessels.
      PPARgamma is a nuclear transcript factor with a very wide spectrum of biological
      activities. It influences important risik factors of atheromathosis, especially
      by patients with metabolic syndrome in diabetes type 2. Thiazolidinediones, which
      is activators PPARgamma, could be a turning-point in the treatment of diabetic
      angiopathy.

PMID- 15850345
TI  - [Contemporary treatment of diabetic foot].
AB  - The management of patients with diabetic foot presents an important challenge for
      health services research. Since today there is no algorithm describingkind of
      diagnostic tests and treatment is the best for patients with different extremity
      ulcers. This article could be helpful for future decisions regarding the
      management of patients with lower extremity ulceration.

PMID- 15850346
TI  - [Clinical use of the interaction between cyclosporine A and its inhibitors].
AB  - This article concerns cyclosporine A and cyclosporine--sparing agents. The drugs
      are evaluated due to their clinical usefulness in elevating cyclosporine blood
      level and their safety in long-term administration. We analyzed imidazole
      antifungal agents, calcium channel blockers and, additionally, pharmacological
      properties of cyclosporine A.

PMID- 15850347
TI  - [The etiopathogenesis of acne vulgaris--if the diet is an important factor?].
AB  - Acne is one of the most common skin diseases. Up till now a lot of research is
      being conduced on the pathogenesis of this disease. Diet is regarded as one of
      the possible, although controversial, co-factors. This work is a review of up-to
      date literature on pathogenesis of acne vulgaris.

PMID- 15850348
TI  - [A case of patient with insulinoma of the pancreas anl infammatory tumor of the
      sigmoid colon-one-step operation treatment].
AB  - The paper presents the case of a 61 year-old man on with a rare disease-
      insulinoma of the pancreas. The tumor was discovered accidentally and it
      displayed no hormonal symptoms. The abdominal pain that the patient had suffered
      from was probably caused by the inflammatory tumor localized in the sigmoid as
      the result of diverticulitis. As the patient had no defecation problems,
      concentration was placed preoperatively on pancreas tumor diagnosis. During the
      operation the pancreas tumor as well as the sigmoid tumor were resected.
      Implantation of the whole profile of pancreas tail to the stomach was performed.
      This method permits for further diagnostics (gastroscopy, ERCP). The man had no
      diabetes, the blood glucose level was normal. The alimentary tract from the
      stomach to the duodenum was kept and the pancreas secretory function was
      acceptable. Colonoscopy in 2002 did not show any pathological changes. One month
      after the operation the patient suffered from pancreatitis which was localized in
      the head of the pancreas. Medical treatment relieved all symptoms, but then the
      cyst in the pancreas head appeared as a sequela. The patient would not agree to
      its puncture. The inflammatory process in the head of the pancreas may have
      resulted from surgical treatment, although ERCP showed no passage obstruction
      between this part of the pancreas and the duodenum. The patient is still on
      follow-up.

PMID- 15850349
TI  - [Multicentric giant cell tumour. The case report].
AB  - The case of a 28 year old woman with multicentric giant cell bone tumours was
      described. Seven tumours' locations were found: Th3, the right and left humerus
      and tibia, the right femur and the right hip bone. All tumours were treated by a
      local resection with a following alcohol adjuvant therapy. Considering young age
      of the patient and multicentric location no radiotherapy was performed. During
      follow up no relapse in long bones and in the hip bone was found. After 6 months
      the relapse in Th3 was reoperated. During the last control examination, the next
      tumour of a distal part of right tibia was found.

PMID- 15850350
TI  - [Ectopic pancreas localized in the stomach].
AB  - The paper presents a case of an ectopic pancreas localized in the wall of the
      pyloric part of the stomach. Preoperative examinations proved ineffective to
      establish the proper diagnosis. The final diagnosis was based on
      histopathological findings of operative preparation.

PMID- 15850351
TI  - [Effects of lingfasu on embryoid and plantlet formation of Panax notoginseng in
      vitro].
AB  - On the medium MS added the right amount of 2,4-D and LFS (Angustmycin) and
      cultured under dark condition, the callus from stem segments of Panax notoginseng
      could induce a lot of embryoids. In 2-3 months, the ratio of embryoid formation
      reached about 90%. Then transplanted on MS + 2,4-D 1.5 mg/L + LFS 2 mg/L and
      cultured under light 20001x, near 30% embryoids could grow and develop as robust
      plantlets.

PMID- 15850352
TI  - [Induction and culture of hairy-root by Agrobacteriun rhizogenes in Dendrobium
      nobile].
AB  - OBJECTIVE: To obtain the hairy-roots of Dendrobium nobile. METHODS: The hairy
      root were obtained by infecting different explants with Agrobacteriun rhizogenes
      A4 and culture conditions of hariy root were optimized. RESULT: The best
      conditions of hairy root culture were 1/2MS medium with sucrose (3%) as carbon
      material and lactalbumin hydrolyze (1g/L) as nitron material.

PMID- 15850353
TI  - [Studies on antioxidant constituents from black tea].
AB  - Qimen black tea has strong inhibitory activity of canola oil oxidation. Four
      antioxidant compounds, theaflavin (TF1), theaflavin-3-gallate (TF2A), theaflavin
      3'-gallate (TF2B) and theaflavin digallate (TF3), were isolated from acetic
      acetate extract of black tea by silica gel and sephadex LH-20 column
      chromatography. TF1, TF2A, TF2B and TF3, have stronger antioxidant activity than
      that of BHT (Butylated hydorxytoluene).

PMID- 15850354
TI  - [Studies on the chemical constituents of the essential oil from the leaves of
      Dalbergia odorifera T. Chen].
AB  - OBJECTIVE: To study the constituents of the essential oil from the leaves of
      Dalbergia odorifera T. Chen. METHOD: The constituent were separated and
      identified by GS-MS. RESULT: 21 compounds from the essential oil were identifed,
      which account for 77.71% of total volatile oils, 21.73% of 2-methoxy-4
      vinylphenol, 13.97% of n-hexadecanoic acid, 6.69% of phenol. CONCLUSION: The
      study provided a chemical basis as a medicinal herb.

PMID- 15850355
TI  - [The effect of the extract from Ranunculus japonicus on [Ca2+]i inside rabbit
      VSMC by serologic pharmacological test].
AB  - OBJECTIVE: To observe the influence of serum containing the extract from
      Ranunculus japonicus (ERj) on the amount of [Ca2+]i inside vascular smooth muscle
      cells (VSMC). METHODS: Serum containing ERj was prepared by serum pharmacological
      method. Cultured VSMCs induced by NE were treated with the serum, and the
      influence of it on the amount [Ca2+]i inside cells indicated with INDO-AM was
      determined. RESULTS: The serum containing ERj could markedly decrease the
      increase of the amount of free [Ca2+]i induced by NE in cultured VSMC.
      CONCLUSION: The serum containing ERj could decrease the intracellular [Ca2+]i.

PMID- 15850356
TI  - [The effect of ultrasonication on immuno-modulating activity of mycelial
      polysaccharide from Cordyceps gunnii].
AB  - OBJECTIVE: To investigate immuno-modulating activity change after mycelial
      polysaccharide from Cordyceps gunnii (MPCG) was depolymerized by ultrasonication.
      METHODS: The effects of MPCG and its depolymerizing mixture on mice spleen
      lymphocytes proliferation, mice peritoneal macrophage (PMphi) phagocytosis and
      cytotoxin T lymphocytes (CTL) activity were studied by MTT method, neutral red
      colorimetry, respectively. RESULTS: In vitro, MPCG depolymerized by
      ultrasonication could more significantly inhibite spleen lymphocytes
      proliferation, PMphi phagocytosis of neutral red and CTL activity in mice than
      MPCG, in particular at doses of 10 microg/ml and 100 microg/ml. Whereas, four
      kinds of depolymerized mixture depolymerized for 1h to 2h and 4h to 8h by
      ultrasonication, respectively, had not evident differences at three various
      doses. CONCLUSION: MPCG was suitable for depolymerizing for 1h to 2h and its
      depolymerized mixture had stronger immuno-modulating activity than MPCG.

PMID- 15850357
TI  - [Experimental study on Sorbaria sorbifolia extract against chronic liver damage
      in rats].
AB  - OBJECTIVE: To study the effects of Sorbaria sorbifolia extract (SSE) on DMN
      induced chronic liver damage in rats. METHODS: Seventy-two rats were divided into
      four groups, normal, model, SSE and colchicin group. Serum hyaluronic (HA) and
      type precollagen (PCIII) were detected by radioimmunoassay. Degrees of fibrosis
      and alpha-smooth muscle actin (alpha-SMA) were determined by histopathology under
      microscope. Hydroxyproline (Hyp) and the markers of liver function were examined
      also. RESULTS: The levels of serum ALT, AST, ALb, AKP in SSE groups were notably
      improved as compared with the model group. Serum HA, PCIII and Hyp of hepatic
      tissue in SSE groups were obviously lower than those of model group. The markers
      of oxidative stress( SOD, MDA, GSH-Px) were strikingly improved also in SSE
      groups. HE stains and alpha-SMA expression showed that the degrees of liver
      fibrosis in SSE groups was slighter than that of model group. There was
      significant difference between the model group and SSE groups (P < 0.05 or P <
      0.01). The rats in SSE groups were better than those of colchinicines group.
      CONCLUSION: SSE is able to protect against DMN-induced chronic liver damage,
      which may act through oxidative stress.

PMID- 15850358
TI  - [Studies on anti-HSV effect of Ficus carica leaves].
AB  - OBJECTIVE: To study the anti-HSV effect of the extract from the leaves of Ficos
      carica. METHODS: The effective ingredient was extracted from the leaves of Ficus
      carica, and the anti-virus effect was observed on Hep-2, BHK21 and PRK cells.
      RESULTS: The water extract from the leaves of Ficus carica possessed distinct
      anti-HSV-1 effect. The MTC was 0.5 mg/ml, TDO was 15 mg/ml, and TI was 30.0. It
      possessed low toxicity and directly killing-virus effect on HSV-1. CONCLUSIONS:
      The leaves of Ficus carica possess anti-HSV-1 effect, and their application on
      the area of medicine, food and drugs has expansive foreground.

PMID- 15850359
TI  - [Study on peparation of anemonin from Ranunculus japonicus Thunb].
AB  - OBJECTIVE: To study the preparation of anemonin from Ranunculus japonicus Thunb.
      METHODS: The best conditions of preparation for anemonin were optimized with
      monosyllabic experiments, such as using the purity of anemonin as a index for
      best selection of dying tempreture and the extraction ratio as another index for
      the concentration of NaCl and extracting times. The structures were clucidated on
      the basis of UV, IR, 1HNMR, 13CNMR, 1H-1H COSY, HMQC and HMQC spectra and
      chemical reactions and the purity is measured by HPLC. RESULTS: The best
      conditions for the extraction techniques of anemonin were 15% NaCl, four
      extracting times, 60 degrees C (0.08 Mpa) for drying. The purity of anemonin was
      99% and yield rate was 0. 72 per thousand. Its quality was controlled.
      CONCLUSION: The preparation techniques are feasible and convenient.

PMID- 15850360
TI  - [Study on extraction process of Radix Bupleuri].
AB  - The orthogonal design was used to optimize extraction process of Radix Bupleuri
      with content of total saponin and yield of the extract as markers. Factors that
      have been chosen were ethanol concentration, ethanol consumption, extraction
      times and extraction time. Each factor had three levels. The result showed that
      the optimum extraction condition was 80% ethanol, 4 times the amount of material,
      refluxing for 4 times, 60 minutes each time. The optimized process was stable and
      workable.

PMID- 15850361
TI  - [The process study on the extraction of irone by supercritical fuilds
      extraction].
AB  - OBJECTIVE: To study the condition for the extraction of irone in Iris tectorum by
      supercritical fluids extraction. METHOD: Conditions for the extraction were
      studied by a systematic method as guided by the content of irone presented in the
      extract. RESULTS: The best SFE conditions were: 0.411 mm raw material powder of
      Iris tectorum, 3% CHCl3 as modifier, temperature of extraction 50 degrees C under
      the pressure of 25 MPa, with CO2 flow rate of 120L/h, the static extracting time
      2 h.

PMID- 15850362
TI  - [Study on optimal extraction process of Yinju sugarless granules with orthogonal
      design].
AB  - OBJECTIVE: To study the extxtraction process of chlorogenic acid from Yinju
      sugarless granules. METHODS: The optimal extraction process was selected with
      orthogonal design. The content of chlorogenic acid in the extract was detremined.
      RESULTS: The content of chlorogenic acid was influenced by frequency of
      extraction, the quantity of water and the concentration of ethanol. CONCLUSIONS:
      The optimal extraction process is extraction 3 times with 10 times water and with
      70% ethanol.

PMID- 15850363
TI  - [Content analysis of bilirubin in niuhuang compound suppository by HPLC].
AB  - OBJECTIVE: To establish a method of determinating content of bilirubin in
      Niuhuang Compound Suppository by HPLC. METHOD: C18 column was used. The mobile
      phase was consisted of dimethylsulfoxide: acetonitrile: 0.5% acetic ammonium
      (1:1.4:1). Detector wavelength was 456 nm. The extraction solution for bilirubin
      was consisted of dlimethylsulfoxide: acetonitrile = 9:4. RESULTS: The linearity
      was obtained over the range of 0.107 - 2.14 microg. The mean recovery was 101.0%,
      RSD = 0.518% (n = 5). CONCLUSION: The method was sensitive, simple and accurate.

PMID- 15850364
TI  - [Studies on the quality standard of "Lu Kang Yin Xing Ye Pian"].
AB  - OBJECTIVE: The quality control method of "Lu Kang Yin Xing Ye Pian" (LKYXYP) was
      studied and established. METHOD: The ginkgolides in LKYXYP were identified by
      TLC. The compounds of fatty acids in Perillae oil were determined by CC/MS.
      Flavones, ginkgolides and ginkgolic acids were determined by HPLC. RESULT: There
      were good linears relationship between the peak area and concentration, r =
      0.999, RSD = 1.2% - 2.5% (n = 5), and recoveries of each composition was above
      95%, the contation was stable in 24h. CONCLUSION: This method is proved to be
      accurate and able to be applied for the quality control of this preparation.

PMID- 15850365
TI  - Vancomycin.

PMID- 15850366
TI  - The effects of surgical fracture fixation on the systemic inflammatory response
      to major trauma.
AB  - Early stabilization of major long bone fractures is beneficial in reducing the
      incidence of acute respiratory distress syndrome and multiple organ failure, both
      of which are caused by activation of the systemic inflammatory response. This
      activation results in tissue recruitment of and injury by circulating
      polymorphonuclear leukocytes. The reasons for clinical benefits of early fracture
      stabilization in major trauma are unknown. Published studies indicate that
      fracture surgery increases the posttraumatic inflammatory response. Major surgery
      to stabilize fractures carries a higher complication rate when performed on
      patients whose hypovolemic shock is not fully corrected. Thus, fracture care
      should be tailored to the patient, not dictated by the injured bone.
      Understanding the impact of fracture surgery on the systemic inflammatory
      response to major trauma is necessary to refine treatment and to apply it
      optimally to all patients.

PMID- 15850367
TI  - Salvage of failed treatment of hip fractures.
AB  - Typically, patients with failed internal fixation of a hip fracture have marked
      pain and disability. These patients may present treatment challenges. Salvage is
      tailored to the anatomic site of the nonunion, the quality of the remaining bone
      and articular surface, and patient factors such as age and activity level. In
      younger patients with either a femoral neck or intertrochanteric fracture
      nonunion with a satisfactory hip joint, treatment typically involves revision
      internal fixation with or without osteotomy or bone grafting. In older patients
      with poor remaining proximal bone stock or a badly damaged hip joint, conversion
      to hip arthroplasty can restore function effectively and reduce pain. For femoral
      head salvage procedures, choosing a fixation device and accurate preoperative
      planning are the major challenges in decision making. For conversion to
      arthroplasty, the major challenges are assessing the need for acetabular
      resurfacing, selecting the femoral implant, and managing the greater trochanter.
      Technical challenges include broken hardware, deformity, and femoral bone
      defects. Attention to technical details can minimize potential complications.

PMID- 15850368
TI  - Manifestations of hereditary multiple exostoses.
AB  - The solitary osteochondroma, a common pediatric bone tumor, is a cartilage-capped
      exostosis. Hereditary multiple exostosis is an autosomal dominant disorder
      manifested by the presence of multiple osteochondromas. Linkage analysis has
      implicated mutations in the EXT gene family, resulting in an error in the
      regulation of normal chondrocyte proliferation and maturation that leads to
      abnormal bone growth. Although exostoses are benign lesions, they are often
      associated with characteristic progressive skeletal deformities and may cause
      clinical symptoms. The most common deformities include short stature, limb-length
      discrepancies, valgus deformities of the knee and ankle, asymmetry of the
      pectoral and pelvic girdles, bowing of the radius with ulnar deviation of the
      wrist, and subluxation of the radiocapitellar joint. For certain deformities,
      surgery can prevent progression and provide correction. Patients with hereditary
      multiple exostosis have a slight risk of sarcomatous transformation of the
      cartilaginous portion of the exostosis.

PMID- 15850369
TI  - Surgical approaches to the posteromedial and posterolateral aspects of the knee.
AB  - Surgical approaches to the posterior aspect of the knee are not commonly needed,
      and their use has become even rarer with the increasing sophistication of
      arthroscopic technology. As a result, physicians in orthopaedic surgical training
      are not often exposed to the practical use of surgical dissection around the
      posterior corners of the knee. For certain procedures, however, greater clinical
      utility and decreased surgical morbidity render focused posterior exposure the
      preferred alternative to the classic popliteal dissection with its wide exposure
      of the popliteal anatomy. Surgical indications include ligament repair or
      reconstruction around the posteromedial or posterolateral aspect of the knee,
      inside-out meniscal repair, posterior cruciate ligament tibial inlay
      reconstruction, and Baker's cyst excision. To minimize complications, these
      focused approaches require adeptness with the complex anatomy of the posterior,
      posteromedial, and posterolateral aspects.

PMID- 15850370
TI  - Use of osteopromotive growth factors, demineralized bone matrix, and ceramics to
      enhance spinal fusion.
AB  - Recently developed materials that can enhance fusion rates for posterolateral
      lumbar arthrodesis may be used alone or in combination with autogenous bone
      grafts. Novel osteopromotive growth factor preparations are currently under
      scrutiny; these include autogenous growth factor concentrate, bovine bone-derived
      osteoinductive protein, and recombinant human MP52. Demineralized bone matrix
      products may enhance or extend grafts. However, few studies, especially
      prospective randomized clinical trials, have assessed their efficacy, so it is
      difficult to compare formulations. Ceramics have been evaluated in animal studies
      and human clinical trials for a variety of applications in spinal surgery. These
      materials function best as bone graft extenders or as bioactive osteoinductive
      material carriers in posterolateral lumbar fusions. They have the advantage of
      variable porosity, low cost, and ease of manufacture. Hydroxyapatite/tricalcium
      phosphate ceramics have been shown to perform as well as autogenous bone grafts
      but with fewer complications.

PMID- 15850371
TI  - Atraumatic disorders of the sternoclavicular joint.
AB  - The sternoclavicular joint is the diarthrodial articulation between the axial and
      appendicular skeletons. It is subject to the same disease processes that occur in
      joints, including degenerative arthritis, rheumatoid arthritis, infection, and
      subluxation. Most of these conditions present with swelling of the joint, which
      may be associated with pain and/or tenderness. Plain radiographs can demonstrate
      changes on both sides of the joint. Because of variations in anatomy, computed
      tomography scans and magnetic resonance images are often necessary to clarify the
      pathology. With the exception of acute infection, most conditions can be managed
      nonsurgically, with joint resection reserved for patients with persistent
      symptoms.

PMID- 15850372
TI  - Structural and catalytic diversity within the amidohydrolase superfamily.
AB  - The amidohydrolase superfamily comprises a remarkable set of enzymes that
      catalyze the hydrolysis of a wide range of substrates bearing amide or ester
      functional groups at carbon and phosphorus centers. The most salient structural
      landmark for this family of hydrolytic enzymes is a mononuclear or binuclear
      metal center embedded within the confines of a (beta/alpha)(8)-barrel structural
      fold. Seven variations in the identity of the specific amino acids that function
      as the direct metal ligands have been structurally characterized by X-ray
      crystallography. The metal center in this enzyme superfamily has a dual
      functionality in the expression of the overall catalytic activity. The scissile
      bond of the substrate must be activated for bond cleavage, and the hydrolytic
      water molecule must be deprotonated for nucleophilic attack. In all cases, the
      nucleophilic water molecule is activated through complexation with a mononuclear
      or binuclear metal center. In the binuclear metal centers, the carbonyl and
      phosphoryl groups of the substrates are polarized through Lewis acid catalysis
      via complexation with the beta-metal ion, while the hydrolytic water molecule is
      activated for nucleophilic attack by interaction with the alpha-metal ion. In the
      mononuclear metal centers, the substrate is activated by proton transfer from the
      active site, and the water is activated by metal ligation and general base
      catalysis. The substrate diversity is dictated by the conformational restrictions
      imposed by the eight loops that extend from the ends of the eight beta-strands.

PMID- 15850373
TI  - Sensitivity of NMR residual dipolar couplings to perturbations in folded and
      denatured staphylococcal nuclease.
AB  - The invariance of NMR residual dipolar couplings (RDCs) in denatured forms of
      staphylococcal nuclease to changes in denaturant concentration or amino acid
      sequence has previously been attributed to the robustness of long-range structure
      in the denatured state. Here we compare RDCs of the wild-type nuclease with those
      of a fragment that retains a folded OB-fold subdomain structure despite missing
      the last 47 of 149 residues. The RDCs of the intact protein and of the truncation
      fragment are substantially different under conditions that favor folded
      structure. By contrast, there is a strong correlation between the RDCs of the
      full-length protein and the fragment under denaturing conditions (6 M urea). The
      RDCs of the folded and unfolded forms of the proteins are uncorrelated. Our
      results suggest that RDCs are more sensitive to structural changes in folded than
      unfolded proteins. We propose that the greater susceptibility of RDCs in folded
      states is a consequence of the close packing of the polypeptide chain under
      native conditions. By contrast, the invariance of RDCs in denatured states is
      more consistent with a disruption of cooperative structure than with the
      retention of a unique long-range folding topology.

PMID- 15850374
TI  - Alternative binding modes of proline-rich peptides binding to the GYF domain.
AB  - Recognition of proline-rich sequences plays an important role for the assembly of
      multiprotein complexes during the course of eukaryotic signal transduction and is
      mediated by a set of protein folds that share characteristic features. The GYF
      (glycine-tyrosine-phenylalanine) domain is known as a member of the superfamily
      of recognition domains for proline-rich sequences. Recent studies on the
      complexation of the CD2BP2-GYF domain with CD2 peptides showed that the peptide
      adopts an extended conformation and forms a polyproline type-II helix involving
      residues Pro4-Pro7 [Freund et al. (2002) EMBO J. 21, 5985-5995]. R/K/GxxPPGxR/K
      is the key signature for the peptides that bind to the GYF domain [Kofler et al.
      (2004) J. Biol. Chem. 279, 28292-28297]. In our combined theoretical and
      experimental study, we show that the peptides adopt a polyproline II helical
      conformation in the unbound form as well as in the complex. From molecular
      dynamics simulations, we identify a novel binding mode for the G8W mutant and the
      wild-type peptide (shifted by one proline in register). In contrast, the
      conformation of the peptide mutant H9M remains close to the experimentally
      derived wild-type GYF-peptide complex. Possible functional implications of this
      altered conformation of the bound ligand are discussed in the light of our
      experimental and theoretical results.

PMID- 15850375
TI  - NMR structure of the natural killer cell receptor 2B4 (CD244): implications for
      ligand recognition.
AB  - 2B4, a transmembrane receptor expressed primarily on natural killer (NK) cells
      and on a subset of CD8(+) T cells, plays an important role in activating NK
      mediated cytotoxicity through its interaction with CD48 on target cells. We
      report here the atomic-resolution structure of the ligand-binding (D1) domain of
      2B4 in solution determined by nuclear magnetic resonance (NMR) spectroscopy. The
      overall main chain structure resembles an immunoglobulin variable (V) domain
      fold, very similar to that seen previously for domain 1 of CD2 and CD4. The
      structure contains nine beta-strands assembled into two beta-sheets
      conventionally labeled DEB and AGFCC'C' '. The six-stranded sheet (AGFCC'C' ')
      contains structural features that may have implications for ligand recognition
      and receptor function. A noncanonical disulfide bridge between Cys2 and Cys99
      stabilizes a long and parallel beta-structure between strand A (residues 3-12)
      and strand G (residues 100-108). A beta-bulge at residues Glu45 and Ile46 places
      a bend in the middle of strand C' that orients two conserved and adjacent
      hydrophobic residues (Ile46 and Leu47) inside the beta-sandwich as seen in other
      V domains. Finally, the FG-loop (implicated in ligand recognition in the CD2-CD58
      complex) is dynamically disordered in 2B4 in the absence of a ligand. We propose
      that ligand binding to 2B4 might stabilize the structure of the FG-loop in the
      ligand complex.

PMID- 15850376
TI  - Conformational state of the SecYEG-bound SecA probed by single tryptophan
      fluorescence spectroscopy.
AB  - The SecYEG complex is a membrane-embedded channel that permits the passage of
      precursor proteins (preproteins) across the inner membrane of Escherichia coli.
      SecA is a molecular motor that associates with the SecYEG pore and drives the
      stepwise translocation of preproteins across the membrane through multiple cycles
      of ATP binding and hydrolysis. We have investigated the conformational state of
      soluble and SecYEG-bound SecA using single tryptophan mutants of SecA. The
      fluorescence spectral properties of the single tryptophans of SecA and their
      accessibility to the quencher acrylamide demonstrate that SecA undergoes a
      conformational change that results in a more compact structure upon binding of
      ATP and binding to the SecYEG pore. In addition, SecYEG-bound SecA undergoes ATP
      dependent conformational changes that are not observed for soluble SecA. These
      data support a model in which binding to the SecYEG channel has a major impact on
      the SecA conformation.

PMID- 15850377
TI  - Scanning malleable transition state ensembles: comparing theory and experiment
      for folding protein U1A.
AB  - Using a variational free energy functional, we calculate the characteristics of
      the transition state ensembles (TSE) for the folding of protein U1A and
      investigate how they respond to thermal and mutational changes. The functional
      directly yields predicted chevron plots both for the wild-type protein and for
      various mutants. The detailed variations of the TSE and changes in chevron plots
      predicted by the theory agree reasonably well with the results of the
      experiments. We also show how to visualize the folding nuclei using 3D isodensity
      plots.

PMID- 15850378
TI  - The micelle-bound structure of an antimicrobial peptide derived from the alpha
      chain of bovine hemoglobin isolated from the tick Boophilus microplus.
AB  - Hemoglobin is known to be a source of peptides involved in several functions. The
      peptide FLSFPTTKTYFPHFDLSHGSAQVKGHGAK (Hb33-61) is a proteolytic product of the
      bovine hemoglobin alpha-chain found in the gut content of the cattle tick,
      Boophilus microplus, and it possesses antimicrobial activity. Since in the past
      we showed that the amidated form of Hb33-61, Hb33-61a, is active against a few
      Gram-positive bacteria and fungi strains at micromolar concentration [Fogaca et
      al. (1999) J. Biol. Chem. 274, 25330-25334], we have been prompted to shed more
      light on its functional and structural features. Here we show that the peptide is
      able to disrupt the bacterial membrane ofMicrococcus luteus A270. As for its
      structure, it has a random conformation in water, and it does not interact with
      zwitterionic micelles. On the other hand, it binds to negatively charged micelles
      acquiring a finite structural organization. The 3D structure of Hb33-61a bound to
      SDS micelles exhibits a nonconventional conformation for an antimicrobial
      peptide. The backbone is characterized by the presence of a beta-turn in the N
      terminus and by a beta-turn followed by a alpha-helical stretch in the C
      terminus. A hinge, whose spatial organization is stabilized by side-chain-side
      chain interactions, joins these two regions. Interestingly, it preserves
      structural features present in the corresponding segment of the bovine hemoglobin
      alpha-chain. Hb33-61a does not possess a well-defined amphipathic nature, and H/D
      exchange experiments show that while the C-terminal region is embedded in the SDS
      micelle, one face of the N-terminal half is partly exposed to the solvent.

PMID- 15850379
TI  - Biosynthesis of covalently bound flavin: isolation and in vitro flavinylation of
      the monomeric sarcosine oxidase apoprotein.
AB  - The covalently bound FAD in native monomeric sarcosine oxidase (MSOX) is attached
      to the protein by a thioether bond between the 8alpha-methyl group of the flavin
      and Cys315. Large amounts of soluble apoenzyme are produced by controlled
      expression in a riboflavin-dependent Escherichia coli strain. A time-dependent
      increase in catalytic activity is observed upon incubation of apoMSOX with FAD,
      accompanied by the covalent incorporation of FAD to approximately 80% of the
      level observed with the native enzyme. The spectral and catalytic properties of
      the reconstituted enzyme are otherwise indistinguishable from those of native
      MSOX. The reconstitution reaction exhibits apparent second-order kinetics (k =
      139 M(-)(1) min(-)(1) at 23 degrees C) and is accompanied by the formation of a
      stoichiometric amount of hydrogen peroxide. A time-dependent reduction of FAD is
      observed when the reconstitution reaction is conducted under anaerobic
      conditions. The results provide definitive evidence for autoflavinylation in a
      reaction that proceeds via a reduced flavin intermediate and requires only
      apoMSOX and FAD. Flavinylation of apoMSOX is not observed with 5-deazaFAD or 1
      deazaFAD, an outcome attributed to a decrease in the acidity of the 8alpha-methyl
      group protons. Covalent flavin attachment is observed with 8-nor-8-chloroFAD in
      an aromatic nucleophilic displacement reaction that proceeds via a quininoid
      intermediate but not a reduced flavin intermediate. The reconstituted enzyme
      contains a modified cysteine-flavin linkage (8-nor-8-S-cysteinyl) as compared
      with native MSOX (8alpha-S-cysteinyl), a difference that may account for its
      approximately 10-fold lower catalytic activity.

PMID- 15850380
TI  - High-resolution crystal structure of manganese peroxidase: substrate and
      inhibitor complexes.
AB  - Manganese peroxidase (MnP) is an extracellular heme enzyme that catalyzes the
      peroxide-dependent oxidation of Mn(II) to Mn(III). The Mn(III) is released from
      the enzyme in complex with oxalate. One heme propionate and the side chains of
      Glu35, Glu39, and Asp179 were identified as Mn(II) ligands in the 2.0 A
      resolution crystal structure. The new 1.45 A crystal structure of MnP complexed
      with Mn(II) provides a more accurate view of the Mn-binding site. New features
      include possible partial protonation of Glu39 in the Mn-binding site and
      glycosylation at Ser336. This is also the first report of MnP-inhibitor complex
      structures. At the Mn-binding site, divalent Cd(II) exhibits octahedral,
      hexacoordinate ligation geometry similar to that of Mn(II). Cd(II) also binds to
      a putative second weak metal-binding site with tetrahedral geometry at the C
      terminus of the protein. Unlike that for Mn(II) and Cd(II), coordination of
      trivalent Sm(III) at the Mn-binding site is octacoordinate. Sm(III) was removed
      from a MnP-Sm(III) crystal by soaking the crystal in oxalate and then
      reintroduced into the binding site. Thus, direct comparisons of Sm(III)-bound and
      metal-free structures were made using the same crystal. No ternary complex was
      observed upon incubation with oxalate. The reversible binding of Sm(III) may be a
      useful model for the reversible binding of Mn(III) to the enzyme, which is too
      unstable to allow similar examination.

PMID- 15850381
TI  - Insight into molecular stability and physiological properties of the diheme
      cytochrome CYC41 from the acidophilic bacterium Acidithiobacillus ferrooxidans.
AB  - The cyc1 gene encoding the soluble dihemic cytochrome c CYC(41) from
      Acidithiobacillus ferrooxidans, an acidophilic organism, has been cloned and
      expressed in Escherichia coli as the host organism. The cytochrome was
      successfully produced and folded only in fermentative conditions: this allowed us
      to determine the molecular basis of the heme insertion at extreme pH. Point
      mutations at two sequence positions (E121 and Y63) were introduced near the two
      hemes in order to assign individual redox potentials to the hemes and to identify
      the interaction sites with the redox partners, rusticyanin and cytochrome
      oxidase. Characterization of mutants E121A, Y63A, and Y63F CYC(41) with
      biochemical and biophysical techniques were carried out. Substitution of tyrosine
      63 by phenylalanine alters the environment of heme B. This result indicates that
      heme B has the lower redox potential. Interaction studies with the two
      physiological partners indicate that CYC(41) functions as an electron wire
      between RCy and cytochrome oxidase. A specific glutamate residue (E121) located
      near heme A is directly involved in the interaction with RCy. A docking analysis
      of CYC(41), RCy, and cytochrome oxidase allowed us to propose a model for the
      complex in agreement with our experimental data.

PMID- 15850382
TI  - Role of the covalent glutamic acid 242-heme linkage in the formation and
      reactivity of redox intermediates of human myeloperoxidase.
AB  - In human myeloperoxidase the heme is covalently attached to the protein via two
      ester linkages between the carboxyl groups of Glu242 and Asp94 and modified
      methyl groups on pyrrole rings A and C of the heme as well as a sulfonium ion
      linkage between the sulfur atom of Met243 and the beta-carbon of the vinyl group
      on pyrrole ring A. In the present study, wild-type recombinant myeloperoxidase
      (recMPO) and the variant Glu242Gln were produced in Chinese hamster ovary cells
      and investigated in a comparative sequential-mixing stopped-flow study in order
      to elucidate the role of the Glu242-heme ester linkage in the individual reaction
      steps of both the halogenation and peroxidase cycle. Disruption of the ester bond
      increased heme flexibility, blue shifted the UV-vis spectrum, and, compared with
      recMPO, decelerated cyanide binding (1.25 x 10(4) versus 1.6 x 10(6) M(-)(1) s(
      )(1) at pH 7 and 25 degrees C) as well as compound I formation mediated by either
      hydrogen peroxide (7.8 x 10(5) versus 1.9 x 10(7) M(-)(1) s(-)(1)) or
      hypochlorous acid (7.5 x 10(5) versus 2.3 x 10(7) M(-)(1) s(-)(1)). The overall
      chlorination and bromination activity of Glu242Gln was 2.0% and 24% of recMPO.
      The apparent bimolecular rate constants of compound I reduction by chloride (65
      M(-)(1) s(-)(1)), bromide (5.4 x 10(4) M(-)(1) s(-)(1)), iodide (6.4 x 10(5) M(
      )(1) s(-)(1)), and thiocyanate (2.2 x10(5) M(-)(1) s(-)(1)) were 500, 25, 21, and
      63 times decreased compared with recMPO. By contrast, Glu242Gln compound I
      reduction by tyrosine was only 5.4 times decreased, whereas tyrosine-mediated
      compound II reduction was 60 times slower compared with recMPO. The effects of
      exchange of Glu242 on electron transfer reactions are discussed.

PMID- 15850383
TI  - X-ray crystal structures of Moorella thermoacetica FprA. Novel diiron site
      structure and mechanistic insights into a scavenging nitric oxide reductase.
AB  - Several members of a widespread class of bacterial and archaeal
      metalloflavoproteins, called FprA, likely function as scavenging nitric oxide
      reductases (S-NORs). However, the only published X-ray crystal structure of an
      FprA is for a protein characterized as a rubredoxin:dioxygen oxidoreductase (ROO)
      from Desulfovibrio gigas. Therefore, the crystal structure of Moorella
      thermoacetica FprA, which has been established to function as an S-NOR, was
      solved in three different states: as isolated, reduced, and reduced, NO-reacted.
      As is the case for D. gigas ROO, the M. thermoacetica FprA contains a solvent
      bridged non-heme, non-sulfur diiron site with five-coordinate iron centers
      bridged by an aspartate, and terminal glutamate, aspartate, and histidine
      ligands. However, the M. thermoacetica FprA diiron site showed four His ligands,
      two to each iron, in all three states, whereas the D. gigas ROO diiron site was
      reported to contain only three His ligands, even though the fourth His residue is
      conserved. The Fe1-Fe2 distance within the diiron site of M. thermoacetica FprA
      remained at 3.2-3.4 A with little or no movement of the protein ligands in the
      three different states and with conservation of the two proximal open
      coordination sites. Molecular modeling indicated that each open coordination site
      can accommodate an end-on NO. This relatively rigid and symmetrical diiron site
      structure is consistent with formation of a diferrous dinitrosyl as the committed
      catalytic intermediate leading to formation of N(2)O. These results provide new
      insight into the structural features that fine-tune biological non-heme diiron
      sites for dioxygen activation vs nitric oxide reduction.

PMID- 15850384
TI  - Calcium-modulated S100 protein-phospholipid interactions. An NMR study of
      calbindin D9k and DPC.
AB  - The cellular functions of several S100 proteins involve specific interactions
      with phospholipids and the cell membrane. The interactions between calbindin
      D(9k) (S100D) and the detergent dodecyl phosphocholine (DPC) were studied using
      NMR spectroscopy. In the absence of Ca(2+), the protein associates with DPC
      micelles. The micelle-associated state has intact helical secondary structures
      but no apparent tertiary fold. At neutral pH, Ca(2+)-loaded calbindin D(9k) does
      not associate with DPC micelles. However, a specific interaction is observed with
      individual DPC molecules at a site close to the linker between the two EF-hands.
      Binding to this site occurs only when Ca(2+) is bound to the protein. A reduction
      in pH in the absence of Ca(2+) increases the stability of the micelle-associated
      state. This along with the corresponding reduction in Ca(2+) affinity causes a
      transition to the micelle-associated state also in the presence of Ca(2+) when
      the pH is lowered. Site-specific analysis of the data indicates that calbindin
      D(9k) has a core of three tightly packed helices (A, B, and D), with a dynamic
      fourth helix (C) more loosely associated. Evidence is presented that the Ca(2+)
      binding characteristics of the two EF-hands are distinctly different in a micelle
      environment. The role of calbindin D(9k) in the cell is discussed, along with the
      broader implications for the function of the S100 protein family.

PMID- 15850385
TI  - Alternative splicing of human insulin-degrading enzyme yields a novel isoform
      with a decreased ability to degrade insulin and amyloid beta-protein.
AB  - Deletion of insulin-degrading enzyme (IDE) in mice causes accumulation of
      cerebral amyloid beta-protein (Abeta), hyperinsulinemia, and glucose intolerance.
      Together with genetic linkage and allelic association of IDE to Alzheimer's
      disease (AD) and type 2 diabetes mellitus (DM2), these findings suggest that IDE
      hypofunction could mediate human disease. To date, no coding mutations have been
      found in the canonical isoform of IDE, suggesting that pathological mutations
      could exist in undiscovered exons or regulatory regions, including untranslated
      regions (UTRs). However, neither isoforms arising from alternative splicing nor
      the UTRs have been described. Here, we systematically characterize human IDE
      mRNAs, identify a novel splice form, and compare its subcellular distribution,
      kinetic properties, and ability to degrade Abeta to the known isoform. Six
      distinct human IDE transcripts were identified, with most of the variance
      attributable to alternative polyadenylation sites. In the novel spliceoform, an
      exon we designate "15b" replaces the canonical exon "15a", and the resultant
      variant is widely expressed. Subcellular fractionation, immunofluorescent
      confocal microscopy, and immunogold-electron microscopy reveal that the 15b-IDE
      protein occurs in both cytosol and mitochondria. Organelle targeting of both
      isoforms is determined by which of two translation start sites is used, and only
      those isoforms utilizing the second site regulate levels of secreted Abeta. 15b
      IDE can exist as a heterodimer with the 15a isoform or as a homodimer. The
      apparent K(m) values of recombinant 15b-IDE for both insulin and Abeta are
      significantly higher and the k(cat) and catalytic efficiency markedly lower than
      those of 15a-IDE. In accord, cells coexpressing beta-amyloid precursor protein
      (APP) and 15b-IDE accumulated significantly more Abeta in their media than those
      expressing APP and 15a-IDE. Our results identify a novel, catalytically
      inefficient form of IDE expressed in brain and non-neural tissues and recommend
      novel regions of the IDE gene in which to search for mutations predisposing
      patients to AD and DM2.

PMID- 15850386
TI  - Essential kinesins: characterization of Caenorhabditis elegans KLP-15.
AB  - Kinesins form a superfamily of molecular motors involved in cell division and
      intracellular transport. Twenty kinesins have been found in the Caenorhabditis
      elegans genome, and four of these belong to the kinesin-14 subfamily, i.e.,
      kinesins with C-terminal motor domains. Three of these kinesin-14s, KLP-15, KLP
      16, and KLP-17, form a distinct subgroup in which KLP-15 and KLP-16 are more than
      90% identical and appear to be related by a relatively recent gene duplication.
      They are essential for meiotic spindle organization and chromosome segregation,
      and are mostly expressed in the germline. With 587 amino acids each, they are
      among the smallest kinesins known. Using bacterially expressed KLP-15 constructs
      with different length extensions preceding the motor domain, we have determined
      in vitro the following characteristic properties: ATPase activity, microtubule
      binding, oligomeric state, microtubule gliding activity, and direction of
      movement. The constructs exhibit a monomer-dimer equilibrium that depends on the
      length of the predicted alpha-helical coiled-coil region preceding the motor
      domain. The longest construct with the complete coiled-coil domain is a stable
      dimer, and the shortest construct with only seven amino acids preceding the motor
      domain is a monomer. In microtubule gliding assays, the monomer is immobile
      whereas the fully dimeric KLP-15 construct supports gliding at 2.3 microm/min and
      moves toward microtubule minus ends, like other members of the kinesin-14
      subfamily studied to date.

PMID- 15850387
TI  - The disulfide linkage and the free sulfhydryl accessibility of acyl-coenzyme
      A:cholesterol acyltransferase 1 as studied by using mPEG5000-maleimide.
AB  - Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is a membrane protein located
      in the endoplasmic reticulum (ER). It plays important roles in cellular
      cholesterol homeostasis. Human ACAT1 (hACAT1) contains nine cysteines (C). To
      quantify and map its disulfide linkage, we performed thiol-specific modifications
      by mPEG(5000)-maleimide (PEG-mal) and iodoacetamide (IA) under denatured
      condition, using extracts that contain wild-type or various single C to A mutant
      hACAT1s. With the wild-type enzyme, seven Cs could be modified before
      dithiothreitol (DTT) treatment; nine Cs could be modified after DTT treatment.
      With the C528A or the C546A enzyme, all eight Cs could be modified before or
      after DTT treatment. With all other remaining single C to A mutant enzymes, six
      Cs could be modified before DTT treatment, and eight Cs could be modified after
      DTT treatment. We next performed Lys-C protease digestion on hACAT1 with a
      hemagglutinin (HA) tag at the C-terminus. The digests were treated with or
      without DTT and analyzed by SDS-PAGE and Western blotting. The two predicted C
      terminal fragments (K496-K531 and N532-F550-HA tag) were trapped as a single
      peptide band, but only when the digests were treated without DTT. Thus, C528 and
      C546 near the enzyme's C-terminus form a disulfide. PEG-mal is impermeable to ER
      membranes. We used PEG-mal to map the localizations of the seven free sulfhydryls
      and the disulfide bond of hACAT1 present in microsomal vesicles. The results show
      that C92 is located on the cytoplasmic side of the ER membrane and the disulfide
      is located in the ER lumen, while all other free Cs are located within the
      hydrophobic region(s) of the enzyme.

PMID- 15850388
TI  - Localized influence of 2'-hydroxyl groups and helix geometry on protein
      recognition in the RNA major groove.
AB  - The local geometry of a DNA helix can influence protein recognition, but the
      sequence-specific features that contribute to helix structure are not fully
      understood, and even less is known about how RNA helix geometry may affect
      protein recognition. To begin to understand how local or global helix structure
      may influence binding in an RNA model system, we generated a series of DNA
      analogues of HIV and BIV TAR RNAs in which ribose sugars were systematically
      substituted in and around the known binding sites for argininamide and a BIV Tat
      arginine-rich peptide, respectively, and measured their corresponding binding
      affinities. For each TAR interaction, binding occurs in the RNA major groove with
      high specificity, whereas binding to the all-DNA analogue is weak and
      nonspecific. Relatively few substitutions are needed to convert either DNA
      analogue of TAR into a high-affinity binder, with the ribose requirements being
      restricted largely to regions that directly contact the ligand. Substitutions at
      individual positions show up to 70-fold differences in binding affinity, even at
      adjacent base pairs, while two base pairs at the core of the BIV Tat peptide-RNA
      interface are largely unaffected by deoxyribose substitution. These results
      suggest that the helix geometries and unique conformational features required for
      binding are established locally and are relatively insulated from effects more
      than one base pair away. It seems plausible that arginine-rich peptides are able
      to adapt to a mosaic helical architecture in which segments as small as single
      base steps may be considered as modular recognition units.

PMID- 15850389
TI  - Redox-dependent structural changes in an engineered heme-copper center in
      myoglobin: insights into chloride binding to CuB in heme copper oxidases.
AB  - The effects of chloride on the redox properties of an engineered binuclear heme
      copper center in myoglobin (Cu(B)Mb) were studied by UV-vis
      spectroelectrochemistry and EPR spectroscopy. A low-spin heme Fe(III)-Cu(I)
      intermediate was observed during the redox titration of Cu(B)Mb only in the
      presence of both Cu(II) and chloride. Upon the first electron transfer to the
      Cu(B) center, one of the His ligands of Cu(B) center dissociates and coordinates
      to the heme iron, forming a six-coordinate low-spin ferric heme center and a
      reduced Cu(B) center. The second electron transfer reduces the ferric heme and
      causes the release of the coordinated His ligand. Thus, the fully reduced state
      of the heme-copper center contains a five-coordinate ferrous heme and a reduced
      Cu(B) center, ready for O(2) binding and reduction to water to occur. In the
      absence of a chloride ion, formation of the low-spin heme species was not
      observed. These redox reactions are completely reversible. These results indicate
      that binding of chloride to the Cu(B) center can induce redox-dependent
      structural changes, and the bound chloride and hydroxide in the heme-copper
      center may play different roles in the redox-linked enzymatic reactions of heme
      copper oxidases, probably because of their different binding affinity to the
      copper center and the relatively high concentration of chloride under
      physiological conditions.

PMID- 15850390
TI  - Construction of cryptogein mutants, a proteinaceous elicitor from Phytophthora,
      with altered abilities to induce a defense reaction in tobacco cells.
AB  - We prepared a series of cryptogein mutants, an elicitor from Phytophthora
      cryptogea, with altered abilities to bind sterols and fatty acids. The induction
      of the early events, i.e., synthesis of active oxygen species and pH changes, in
      suspension tobacco cells by these mutated proteins was proportional to their
      ability to bind sterols but not fatty acids. Although the cryptogein-sterol
      complex was suggested to be a form triggering a defense reaction in tobacco, some
      proteins unable to bind sterols induced the synthesis of active oxygen species
      and pH changes. The modeling experiments showed that conformational changes after
      the introduction of bulky residues into the omega loop of cryptogein resemble
      those induced by sterol binding. These changes may be necessary for the ability
      to trigger the early events by elicitins. However, the ability to stimulate
      necrosis in suspension tobacco cells and the expression of defense proteins in
      tobacco plants were linked neither to the lipid binding capacity nor to the
      capacity to provoke the early events. On the basis of these experiments and
      previous results, we propose that elicitins could stimulate two signal pathways.
      The first one induces necroses and the expression of pathogen-related proteins,
      includes tyrosine protein kinases and mitogen-activated protein kinases, and
      depends on the overall structure and charge distribution. The second type of
      interaction is mediated by phospholipase C and protein kinase C. It triggers the
      synthesis of active oxygen species and pH changes. This interaction depends on
      the ability of elicitins to bind sterols.

PMID- 15850391
TI  - Recognition and activation of Rho GTPases by Vav1 and Vav2 guanine nucleotide
      exchange factors.
AB  - Vav proteins are Rho GTPase-specific guanine nucleotide exchange factors (GEFs)
      that are distinguished by the tandem arrangement of Dbl homology (DH), Pleckstrin
      homology (PH), and cysteine rich domains (CRD). Whereas the tandem DH-PH
      arrangement is conserved among Rho GEFs, the presence of the CRD is unique to Vav
      family members and is required for efficient nucleotide exchange. We provide
      evidence that Vav2-mediated nucleotide exchange of Rho GTPases follows the
      Theorell-Chance mechanism in which the Vav2.Rho GTPase complex is the major
      species during the exchange process and the Vav2.GDP-Mg(2+).Rho GTPase ternary
      complex is present only transiently. The GTPase specificity for the DH-PH-CRD
      Vav2 in vitro follows this order: Rac1 > Cdc42 > RhoA. Results obtained from
      fluorescence anisotropy and NMR chemical shift mapping experiments indicate that
      the isolated Vav1 CRD is capable of directly associating with Rac1, and residues
      K116 and S83 that are in the proximity of the P-loop and the guanine base either
      are part of this binding interface or undergo a conformational change in response
      to CRD binding. The NMR studies are supported by kinetic measurements on Rac1
      mutants S83A, K116A, and K116Q and Vav2 CRD mutant K533A in that these mutants
      affect both the initial binding event of Vav2 with Rac1 (k(on)) and the rate
      limiting dissociation of Vav2 from the Vav2.Rac1 binary complex (thereby
      influencing the enzyme turnover number, k(cat)). The results suggest that the CRD
      domain in Vav proteins plays an active role, affecting both the k(on) and the
      k(cat) for Vav-mediated nucleotide exchange on Rho GTPases.

PMID- 15850392
TI  - Enzymatic characterization of membrane-associated hepatitis C virus NS3-4A
      heterocomplex serine protease activity expressed in human cells.
AB  - The hepatitis C virus (HCV) nonstructural (NS)3-NS4A serine protease
      heterocomplex is a prime target for development of novel HCV therapies, due to
      its essential role in maturation of the viral polyprotein. While the mode of
      substrate/inhibitor recognition of the HCV NS3/NS4A serine protease has been
      extensively studied in vitro, important molecular aspects of the mechanism of
      action for this membrane-bound multifunctional enzyme remain unresolved in vivo.
      In particular, what influence does membrane association exert on the specificity
      and catalysis of NS3-4A protease? To carry out this study, we developed a
      specific and sensitive protease assay using a unique internally quenched
      fluorogenic substrate (IQFS). Our IQFS enables for the first time the direct,
      specific detection of NS3-4A protease activity within membrane fractions isolated
      from human cells expressing NS3-4A and the determination of its steady-state
      kinetic parameters, which were found to be K(m) = 51 +/- 3 microM and k(cat) =
      0.39 min(-1). We also show that our fluorescence-based bioassay can be used to
      evaluate specifically the potency and mode of action of NS3-4A directed
      inhibitors, such as in the case of a known NS3-4A substrate-analogue inhibitor
      (K(i) = 22 nM). Our results indicate that the membrane anchoring of NS3 by NS4A
      does not affect the substrate/inhibitor recognition by the NS3-4A protease
      domain. Further investigation may reveal whether membrane association could be
      important for regulating other enzymatic activities associated with NS3 (e.g.,
      helicase and/or ATPase) and/or regulating the recently proposed cross-talk
      between the protease and helicase activities.

PMID- 15850393
TI  - Ligand-free and -bound structures of the binding protein (LivJ) of the
      Escherichia coli ABC leucine/isoleucine/valine transport system: trajectory and
      dynamics of the interdomain rotation and ligand specificity.
AB  - The leucine/isoleucine/valine-binding protein (LIVBP or LivJ) serves as the
      primary high-affinity receptor of the Escherichia coli ABC-type transporter for
      the three aliphatic amino acids. The first structure of LIVBP determined
      previously without bound ligand showed a molecule comprised of two domains which
      are far apart and bisected by a wide open, solvent-accessible cleft. Here we
      report the crystal structures of another ligand-free state and three complexes
      with the aliphatic amino acids. In the present ligand-free structure, the two
      domains are farther apart. In the three very similar complex structures, the two
      domains are in close proximity, and each desolvated ligand is completely engulfed
      in the cleft and bound by both domains. The two different ligand-free structures,
      combined with those of the very similar ligand-bound structures, indicate the
      trajectory and backbone torsion angle changes of the hinges that accompany domain
      closure and play crucial functional roles. The amino acids are bound by polar and
      nonpolar interactions, occurring predominantly in one domain. Consistent with the
      protein specificity, the aliphatic side chains of the ligands lie in a
      hydrophobic pocket fully formed following domain or cleft closure. Comparison of
      the structures of LIVBP with several different binding proteins indicates no
      correlations between the magnitudes of the hinge-bending angles and the protein
      masses, the ligand sizes, or the number of segments connecting the two domains.
      Results of normal-mode analysis and molecular dynamics simulations are consistent
      with the trajectory and intrinsic flexibility of the interdomain hinges and the
      dominance of one domain in ligand binding in the open state.

PMID- 15850394
TI  - Improved catalytic properties of halohydrin dehalogenase by modification of the
      halide-binding site.
AB  - Halohydrin dehalogenase (HheC) from Agrobacterium radiobacter AD1 catalyzes the
      dehalogenation of vicinal haloalcohols by an intramolecular substitution
      reaction, resulting in the formation of the corresponding epoxide, a halide ion,
      and a proton. Halide release is rate-limiting during the catalytic cycle of the
      conversion of (R)-p-nitro-2-bromo-1-phenylethanol by the enzyme. The recent
      elucidation of the X-ray structure of HheC showed that hydrogen bonds between the
      OH group of Tyr187 and between the Odelta1 atom of Asn176 and Nepsilon1 atom of
      Trp249 could play a role in stabilizing the conformation of the halide-binding
      site. The possibility that these hydrogen bonds are important for halide binding
      and release was studied using site-directed mutagenesis. Steady-state kinetic
      studies revealed that mutant Y187F, which has lost both hydrogen bonds, has a
      higher catalytic activity (k(cat)) with two of the three tested substrates
      compared to the wild-type enzyme. Mutant W249F also shows an enhanced k(cat)
      value with these two substrates, as well as a remarkable increase in
      enantiopreference for (R)-p-nitro-2-bromo-1-phenylethanol. In case of a mutation
      at position 176 (N176A and N176D), a 1000-fold lower catalytic efficiency
      (k(cat)/K(m)) was obtained, which is mainly due to an increase of the K(m) value
      of the enzyme. Pre-steady-state kinetic studies showed that a burst of product
      formation precedes the steady state, indicating that halide release is still rate
      limiting for mutants Y187F and W249F. Stopped-flow fluorescence experiments
      revealed that the rate of halide release is 5.6-fold higher for the Y187F mutant
      than for the wild-type enzyme and even higher for the W249F enzyme. Taken
      together, these results show that the disruption of two hydrogen bonds around the
      halide-binding site increases the rate of halide release and can enhance the
      overall catalytic activity of HheC.

PMID- 15850395
TI  - Structural studies on the reaction of isopenicillin N synthase with the truncated
      substrate analogues delta-(L-alpha-aminoadipoyl)-L-cysteinyl-glycine and delta-(L
      alpha-aminoadipoyl)-L-cysteinyl-D-alanine.
AB  - Isopenicillin N synthase (IPNS), a non-heme iron(II)-dependent oxidase, catalyzes
      conversion of the tripeptide delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-valine
      (ACV) to bicyclic isopenicillin N (IPN), concomitant with the reduction of
      dioxygen to two molecules of water. Incubation of the "truncated"substrate
      analogues delta-(l-alpha-aminoadipoyl)-l-cysteinyl-glycine (ACG) and delta-(l
      alpha-aminoadipoyl)-l-cysteinyl-d-alanine (ACA) with IPNS has previously been
      shown to afford acyclic products, in which the substrate cysteinyl residue has
      undergone a two-electron oxidation. We report X-ray crystal structures for the
      anaerobic IPNS/Fe(II)/ACG and IPNS/Fe(II)/ACA complexes, both in the absence and
      presence of the dioxygen analogue nitric oxide. The overall protein structures
      are very similar to those of the corresponding IPNS/Fe(II)/ACV complexes;
      however, significant differences are apparent in the vicinity of the active site
      iron. The structure of the IPNS/Fe(II)/ACG complex reveals that the C-terminal
      carboxylate of this substrate is oriented toward the active site iron atom,
      apparently hydrogen-bonded to an additional water ligand at the metal; this is a
      different binding mode to that observed in the IPNS/Fe(II)/ACV complex. ACA binds
      to the metal in a manner that is intermediate between those observed for ACV and
      ACG. The addition of NO to these complexes initiates conformational changes such
      that both the IPNS/Fe(II)/ACG/NO and IPNS/Fe(II)/ACA/NO structures closely
      resemble the IPNS/Fe(II)/ACV/NO complex. These results further demonstrate the
      feasibility of metal-centered rearrangements in catalysis by non-heme iron
      enzymes and provide insight into the delicate balance between hydrophilic
      hydrophobic interactions and steric effects in the IPNS active site.

PMID- 15850396
TI  - Ligand-mediated anticodon conformational changes occur during tRNA methylation by
      a TrmD methyltransferase.
AB  - Orthologs of TrmD, G37 tRNA methyltransferases, have been analyzed with regard to
      post-tRNA binding events required to move the residue G37 in proximity to bound
      AdoMet for catalysis. This was approached initially by probing tRNA with T2
      nuclease or Pb acetate in the presence, then absence, of Escherichia coli TrmD
      protein. Cleavage patterns clearly show that portions of the anticodon loop
      phosphodiester backbone are protected from cleavage only in the presence of
      sinefungin, a potent AdoMet analogue. This demonstrates that there must be
      considerable movement of the loop region and/or protein as the AdoMet site is
      occupied. Florescence energy transfer experiments were employed to better assess
      the movement of the G37 and G36 base residues in response to occupancy of the
      AdoMet site. When the Streptococcus pneumoniae TrmD protein was bound to
      synthetic tRNA(1)(Leu) substituted with 2-aminopurine at positions 36 and 37,
      fluorescence energy transfer analysis showed that a decrease in 2-aminopurine
      fluorescence occurs only when AdoMet is present. Taken together, these results
      suggest that the base to be methylated by the TrmD protein is mobilized into the
      active center after tRNA binding only when the AdoMet site is occupied.

PMID- 15850397
TI  - Inhibition and pH dependence of phosphite dehydrogenase.
AB  - Phosphite dehydrogenase (PTDH) catalyzes the NAD-dependent oxidation of phosphite
      to phosphate, a reaction that is 15 kcal/mol exergonic. The enzyme belongs to the
      family of D-hydroxy acid dehydrogenases. Five other family members that were
      analyzed do not catalyze the oxidation of phosphite, ruling out the possibility
      that this is a ubiquitous activity of these proteins. PTDH does not accept any
      alternative substrates such as thiophosphite, hydrated aldehydes, and
      methylphosphinate, and potential small nucleophiles such as hydroxylamine,
      fluoride, methanol, and trifluoromethanol do not compete with water in the
      displacement of the hydride from phosphite. The pH dependence of
      k(cat)/K(m,phosphite) is bell-shaped with a pK(a) of 6.8 for the acidic limb and
      a pK(a) of 7.8 for the basic limb. The pK(a) of 6.8 is assigned to the second
      deprotonation of phosphite. However, whether the dianionic form of phosphite is
      the true substrate is not clear since a reverse protonation mechanism is also
      consistent with the available data. Unlike k(cat)/K(m,phosphite), k(cat) and
      k(cat)/K(m,NAD) are pH-independent. Sulfite is a strong inhibitor of PTDH that is
      competitive with respect to phosphite and uncompetitive with respect to NAD(+).
      Incubation of the enzyme with NAD(+) and low concentrations of sulfite results in
      a covalent adduct between NAD(+) and sulfite in the active site of the enzyme
      that binds very tightly. Fluorescent titration studies provided the apparent
      dissociation constants for NAD(+), NADH, sulfite, and the sulfite-NAD(+) adduct.
      Substrate isotope effect studies with deuterium-labeled phosphite resulted in
      small normal isotope effects (1.4-2.1) on both k(cat) and k(cat)/K(m,phosphite)
      at pH 7.25 and 8.0. Solvent isotope effects (SIEs) on k(cat) are similar in size;
      however, the SIE of k(cat)/K(m,phosphite) at pH 7.25 is significantly larger
      (4.4), whereas at pH 8.0, it is the inverse (0.6). The pH-rate profile of
      k(cat)/K(m,phosphite), which predicts that the observed SIEs will have a
      significant thermodynamic origin, can account for these effects.

PMID- 15850398
TI  - Functional characterization of N-terminal nucleotide binding domain (NBD-1) of a
      major ABC drug transporter Cdr1p of Candida albicans: uncommon but conserved
      Trp326 of Walker B is important for ATP binding.
AB  - Using purified N-terminal NBD (NBD-512) domain of Cdr1p, a major multidrug
      extrusion pump of human pathogenic yeast Candida albicans, we show the relevance
      of the unique positioning of an atypical Trp326 residue. Similar to Cys193 in
      Walker A, Trp326 in the Walker B motif of Cdr1p is also a conserved feature of
      other fungal ATP Binding Cassette (ABC) transporters. By employing fluorescence
      spectroscopy, chemical modification, and site-directed mutagenesis, we
      demonstrate that of the five Trp residues in the NBD-512 domain, Trp326 alone is
      important for nucleotide binding and subsequent conformational changes within the
      domain. Furthermore, mutation of Trp326 to Ala results in an increased K(M)
      without appreciably affecting V(max) of ATPase activity. Thus, Trp326 in NBD-512
      appears to be important for nucleotide binding and not for its hydrolysis.
      Additionally, the role of Trp326 in ATP binding is independent of the presence of
      the adjacent well-conserved Asp327 residue which, like Cys193, has a catalytic
      role in ATP hydrolysis. Considering that Trp326 of Cdr1p is a typical feature of
      fungal transporters alone, our study suggests that these ABC transporters may
      reflect mechanistic differences with regard to nucleotide binding and hydrolysis
      as compared to their counterparts of non-fungal origin.

PMID- 15850399
TI  - Domain-mediated dimerization of the Hsp90 cochaperones Harc and Cdc37.
AB  - Hsp90 is a highly conserved molecular chaperone that acts in concert with Hsp70
      and a cohort of cochaperones to mediate the folding of client proteins into
      functional conformations. The novel Hsp90 cochaperone Harc was identified
      previously on the basis of its amino acid sequence similarity to Cdc37. Although
      the biochemical role of Harc has not been established, the structural
      similarities between Harc and Cdc37 suggest that it too may function to regulate
      the binding of client proteins to Hsp90. We report here that Harc forms dimers in
      vitro. Functional dissection of Harc revealed that both the N-terminal and middle
      domains contributed to its dimerization. Notably, dimerization of the middle
      domain of Harc was required for the binding of Hsp90, suggesting that dimerized
      Harc binds to Hsp90 dimers. The N-terminal domain of Harc made an important
      contribution to the dimerization of Harc by facilitating the interaction of Hsp70
      with Harc-Hsp90 heterocomplexes. Harc was also found to heterodimerize with Cdc37
      in vitro. Titration experiments revealed that Harc homodimerization was favored
      over heterodimerization with Cdc37 when both cochaperones were at similar levels.
      However, formation of Harc homodimers and heterodimers of Harc and Cdc37 was
      comparable when the level of Cdc37 was approximately 10-fold above that of Harc.
      Furthermore, homo- and heterodimerization of Harc and Cdc37 was a dynamic
      process. Thus Harc could potentially contribute to the regulation of the Hsp90
      mediated folding of Cdc37-dependent protein kinases into functional conformations
      via dimerization with Cdc37.

PMID- 15850400
TI  - Multiple enzyme activities of Escherichia coli MutT protein for sanitization of
      DNA and RNA precursor pools.
AB  - 8-OxoGua (8-oxo-7,8-dihydroguanine) is produced in nucleic acids as well as in
      nucleotide pools of cells, by reactive oxygen species normally formed during
      cellular metabolic processes. MutT protein of Escherichia coli specifically
      degrades 8-oxoGua-containing deoxyribo- and ribonucleoside triphosphates to
      corresponding nucleoside monophosphates, thereby preventing misincorporation of 8
      oxoGua into DNA and RNA, which would cause mutation and phenotypic suppression,
      respectively. Here, we report that the MutT protein has additional activities for
      cleaning up the nucleotide pools to ensure accurate DNA replication and
      transcription. It hydrolyzes 8-oxo-dGDP to 8-oxo-dGMP with a K(m) of 0.058
      microM, a value considerably lower than that for its normal counterpart, dGDP
      (170 microM). Furthermore, the MutT possesses an activity to degrade 8-oxo-GDP to
      the related nucleoside monophosphate, with a K(m) value 8000 times lower than
      that for GDP. These multiple enzyme activities of the MutT protein would
      facilitate the high fidelity of DNA and RNA syntheses.

PMID- 15850401
TI  - Uncovering the enzymatic pKa of the ribosomal peptidyl transferase reaction
      utilizing a fluorinated puromycin derivative.
AB  - The ribosome-catalyzed peptidyl transferase reaction displays a complex pH
      profile resulting from two functional groups whose deprotonation is important for
      the reaction, one within the A-site substrate and a second unidentified group
      thought to reside in the rRNA peptidyl transferase center. Here we report the
      synthesis and activity of the beta,beta-difluorophenylalanyl derivative of
      puromycin, an A-site substrate. The fluorine atoms reduce the pK(a) of the
      nucleophilic alpha-amino group (<5.0) such that it is deprotonated at all pHs
      amenable to ribosomal analysis (pH 5.2-9.5). In the 50S modified fragment assay,
      this substrate reacts substantially faster than puromycin at neutral or acidic
      pH. The reaction follows a simplified pH profile that is dependent only upon
      deprotonation of a titratable group within the ribosomal active site. This
      feature will simplify characterization of the peptidyl transferase reaction
      mechanism. On the basis of the reaction efficiency of the doubly fluorinated
      substrate compared to the unfluorinated derivative, the Bronsted coefficient for
      the nucleophile is estimated to be substantially smaller than that reported for
      uncatalyzed aminolysis reactions, which has important mechanistic implications
      for the peptidyl transferase reaction.

PMID- 15850402
TI  - Characterization of kinetic folding intermediates of recombinant canine milk
      lysozyme by stopped-flow circular dichroism.
AB  - The intermediate in the equilibrium unfolding of canine milk lysozyme induced by
      a denaturant is known to be very stable with characteristics of the molten
      globule state. Furthermore, there are at least two kinetic intermediates during
      refolding of this protein: a burst-phase (first) intermediate formed within the
      dead time of stopped-flow measurements and a second intermediate that accumulates
      with a rate constant of 22 s(-)(1). To clarify the relationships of these
      intermediates with the equilibrium intermediate, and also to characterize the
      structural changes of the protein during refolding, here we studied the kinetic
      refolding reactions using stopped-flow circular dichroism at 10 different
      wavelengths and obtained the circular dichroism spectra of the intermediates.
      Comparison of the circular dichroism spectra of the intermediates, as well as the
      absence of observed kinetics in the refolding from the fully unfolded state to
      the equilibrium intermediate, has demonstrated that the burst-phase intermediate
      is equivalent to the equilibrium intermediate. The difference circular dichroism
      spectrum that represented changes from the kinetic intermediate to the native
      state had characteristics of an exciton coupling band, indicating that specific
      packing of tryptophan residues in this protein occurred in this phase. From these
      findings, we propose a schematic model of the refolding of canine milk lysozyme
      that is consistent with the hierarchical mechanism of protein folding.

PMID- 15850403
TI  - Differential docking of high-affinity peptide ligands to type A and B
      cholecystokinin receptors demonstrated by photoaffinity labeling.
AB  - Type A and B cholecystokinin (CCK) receptors are highly homologous members of the
      class-I family of G protein-coupled receptors that bind CCK with high affinity.
      However, they have divergent structural specificities, with the type A receptor
      requiring seven carboxyl-terminal residues including a sulfated tyrosine and the
      type B receptor requiring only the carboxyl-terminal tetrapeptide. The aim of
      this work was to utilize affinity labeling to determine spatial approximations
      with photolabile p-benzoyl-l-phenylalanine (Bpa) residues sited at each end of
      CCK as docked at the type B CCK receptor, contrasting this with analogous work
      using similar probes docked at the type A receptor. Both probes were fully
      efficacious, potent agonists that stimulated intracellular calcium in receptor
      bearing CHO-CCKBR cells (EC(50) values: Bpa(24) probe, 41 +/- 9 pM; Bpa(33)
      probe, 15 +/- 3.3 pM). They bound specifically, with high affinity (K(i) values:
      Bpa(24) probe, 0.60 +/- 0.17 nM; Bpa(33) probe, 0.58 +/- 0.11 nM). Cyanogen
      bromide cleavage of the covalently labeled receptor suggested the first
      extracellular loop as the region of labeling by each probe, distinct from the
      type A CCK receptor regions labeled using the same probes (third loop and amino
      terminal tail, respectively). This was confirmed by subsequent enzymatic and
      chemical cleavage of labeled wild-type and mutant receptors. Sequential cycles of
      Edman degradation of labeled receptor fragments identified the specific residues
      within loop one labeled by each probe (Bpa(24) probe labeled Phe(122); Bpa(33)
      probe labeled Thr(119)). This provides a direct demonstration of distinct modes
      of docking the same high-affinity ligand to highly homologous receptors.

PMID- 15850404
TI  - Kinetics of folding of Escherichia coli OmpA from narrow to large pore
      conformation in a planar bilayer.
AB  - The outer membrane protein of Escherichia coli, OmpA, is currently alleged to
      adopt two native conformations: a major two-domain conformer in which 171 N
      terminal residues form a narrow eight beta-barrel pore and 154 C-terminal
      residues are in the periplasm and a minor one-domain conformer in which all 325
      residues create a large pore. However, recent studies in planar bilayers indicate
      the conformation of OmpA is temperature-sensitive and that increasing temperature
      converts narrow pores to large pores. Here we examine the reversibility and
      kinetics of this transition for single OmpA molecules in planar bilayers of
      diphytanoylphosphatidylcholine (DPhPC). We find that the transition is
      irreversible. When temperatures are decreased, large pores close down, and when
      temperatures are stabilized they reopen in the large pore conformation, with
      gradually increasing open time. Large pores are converted to narrow pores only by
      denaturing agents. The transition from narrow to large pores requires
      temperatures >or= 26 degrees C and is a biphasic process with rates that rise
      steeply with temperature. The first phase, a flickering stepwise transition from
      a low-conductance to a high-conductance state requires approximately 7 h at 26
      degrees C but only approximately 13 min at 42 degrees C, signifying an activation
      energy of 139 +/- 12 kJ/mol. This is followed by a gradual increase in
      conductance and open probability, interpreted as optimization of the large pore
      structure. The results indicate that the two-domain structure is a partially
      folded intermediate that is kinetically stable at lower temperatures and that
      mature fully folded OmpA is a large pore.

PMID- 15850405
TI  - A novel genomic approach identifies bacterial DNA-dependent RNA polymerase as the
      target of an antibacterial oligodeoxynucleotide, RBL1.
AB  - Rapid emergence of antibiotic-resistant bacterial pathogens limits the
      applicability of existing drugs, which has created an urgent need for novel
      antibiotics preferably with entirely new mechanisms of action.
      Oligodeoxynucleotides (ODNs) and their modified forms have been shown to inhibit
      bacterial gene expression, representing a potential for developing highly
      specific and efficacious antibacterial agents. In this study, a tetracycline
      (Tet)-inducible, randomized single-stranded DNA (ssDNA) expression library was
      constructed and screened for conditional growth-defective or lethal phenotypes in
      an Escherichia coli system. From approximately 5000 transformants screened, 12
      bacterial colonies were identified with either growth-defective or lethal
      phenotypes. One clone, CY01, with a lethal phenotype was selected and sequenced,
      and the ODN sequence that it generates was designated as RBL-1. Because RBL-1
      shows no significant homologies to any bacterial gene sequence, a potential RBL-1
      targeting protein was isolated by affinity purification. Using mass spectrometry
      analysis, this protein was identified as bacterial DNA-dependent RNA polymerase
      (RNAP). RBL-1 was further shown to effectively inhibit RNA polymerase activity in
      vitro. The usage of this randomized ssDNA expression library screening technology
      to selectively modulate production and/or function of proteins may provide a
      powerful strategy in both identifying novel gene targets for antibiotic discovery
      and developing novel antibacterial agents.

PMID- 15850406
TI  - Intrinsic isomerase activity of medium-chain acyl-CoA dehydrogenase.
AB  - Mitochondrial medium-chain acyl-CoA dehydrogenase is a key enzyme for the beta
      oxidation of fatty acids, and the deficiency of this enzyme in patients has been
      previously reported. We found that the enzyme has intrinsic isomerase activity,
      which was confirmed using incubation followed with HPLC analysis. The isomerase
      activity of the enzyme was thoroughly characterized through studies of kinetics,
      substrate specificity, pH dependence, and enzyme inhibition. E376 mutants were
      constructed, and mutant enzymes were purified and characterized. It was shown
      that E376 is the catalytic residue for both dehydrogenase and isomerase
      activities of the enzyme. The isomerase activity of medium-chain acyl-CoA
      dehydrogenase is probably a spontaneous process driven by thermodynamic
      equilibrium with the formation of a conjugated structure after deprotonation of
      substrate alpha proton. The energy level of the transition state may be lowered
      by a stable dienolate intermediate, which gains further stabilization via charge
      transfer with the electron-deficient FAD cofactor of the enzyme. This raises the
      question as to whether the dehydrogenase might function as an isomerase in vivo
      in conditions in which the activity of the isomerase is decreased.

PMID- 15850407
TI  - Why we need to rethink the diseases of affluence.

PMID- 15850408
TI  - Pravastatin limits endothelial activation after irradiation and decreases the
      resulting inflammatory and thrombotic responses.
AB  - Endothelial dysfunction has been implicated in the pathogenesis of
      atherosclerosis, fibrosis and vascular occlusion after radiation therapy. Statins
      have been reported to improve endothelial function; however, this beneficial
      effect on endothelial cells has never been investigated after irradiation.
      Therefore, using human microvascular endothelial cells from lung that had been
      irradiated with 5 or 10 Gy, we assessed the effect of pravastatin on endothelial
      activation by ELISA, cell-ELISA and electrophoretic mobility shift assay and
      increased blood-endothelial cell interactions by a flow adhesion assay.
      Pravastatin inhibited the overproduction of monocyte chemoattractant protein 1,
      IL6 and IL8 and the enhanced expression of intercellular adhesion molecule 1 but
      had no effect on platelet-endothelial cell adhesion molecule 1 expression.
      Moreover, pravastatin down-regulated the radiation-induced activation of the
      transcription factor activator protein 1 but not of nuclear factor-kappaB.
      Finally, an inhibition by pravastatin of increased adhesion of leukocytes and
      platelets to irradiated endothelial cells was observed. The effect of pravastatin
      was maintained up to 14 days after irradiation and was reversed by mevalonate.
      Pravastatin exerts persistent anti-inflammatory and anti-thrombotic effects on
      irradiated endothelial cells. Statins may be considered in therapeutic strategies
      for the management of patients treated with radiation therapy.

PMID- 15850409
TI  - Novel HDAC inhibitors with radiosensitizing properties.
AB  - The members of the histone deacetylase (HDAC) family play important roles in
      various cellular processes, including transcriptional regulation, cell
      proliferation, differentiation and apoptosis. Inhibitors of histone deacetylases
      are emerging as an important new class of chemotherapeutic agents. As such,
      identifying stable and potent chemical HDAC inhibitory compounds is an important
      focus for translational research. Here we report the results of a rational drug
      design of novel HDAC inhibitors with potential for sensitizing cancer cells to
      radiation therapy. Over 60 HDAC inhibitor analogues incorporating a urea backbone
      and the hydroxamic acid end moiety were designed and screened. Six were found to
      confer 50% inhibition of HDAC enzyme activity at nanomolar concentrations. These
      candidate HDAC inhibitors inhibited cell proliferation at the ranges of IC50 10
      50 microM in various cancer cells, including prostate (PC-3), breast (MCF-7) and
      head and neck squamous carcinoma (SQ-20B). Furthermore, radiation clonogenic
      survival assays revealed that these compounds possess radiosensitizing properties
      that are cell type-specific. The data support the further investigation of these
      HDAC inhibitors for use as sensitizing agents with potential for clinical
      application.

PMID- 15850410
TI  - LET and ion species dependence for cell killing in normal human skin fibroblasts.
AB  - We studied the LET and ion species dependence of the RBE for cell killing to
      clarify the differences in the biological effects caused by the differences in
      the track structure that result from the different energy depositions for
      different ions. Normal human skin fibroblasts were irradiated with heavy-ion
      beams such as carbon, neon, silicon and iron ions that were generated by the
      Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of
      Radiological Science (NIRS) in Japan. Cell killing was measured as reproductive
      cell death using a colony formation assay. The RBE-LET curves were different for
      carbon ions and for the other ions. The curve for carbon ions increased steeply
      up to around 98 keV/microm. The RBE of carbon ions at 98 keV/microm was 4.07. In
      contrast, the curves for neon, silicon and iron ions had maximum peaks around 180
      keV/microm, and the RBEs at the peak position ranged from 3.03 to 3.39. When the
      RBEs were plotted as a function of Z*2/beta2 (where Z* is the effective charge
      and beta is the relative velocity of the ion) instead of LET, the discrepancies
      between the RBE-LET curves for the different ion beams were reduced, but
      branching of the RBE-Z*2/beta2 curves still remained. When the inactivation cross
      section was plotted as a function of either LET or Z*2/beta2, it increased with
      increasing LET. However, the inactivation cross section was always smaller than
      the geometrical cross section. These results suggest that the differences in the
      energy deposition track structures of the different ion sources have an effect on
      cell killing.

PMID- 15850411
TI  - Relative biological effectiveness of 103Pd and 125I photons for continuous low
      dose-rate irradiation of Chinese hamster cells.
AB  - Monolayers of Chinese hamster lung cells (CCL-16) in a polystyrene phantom were
      irradiated in vitro by 103Pd and 125I sources at dose rates of 6 to 72 cGy/h.
      Cell survival curves for acute high-dose-rate irradiation (over 30 Gy/h) were
      also measured using nearly monoenergetic X-ray beams which were designed to
      simulate the mean energies of photons emitted by 125I and 103Pd and also using a
      clinical 250 kVp X-ray beam. A profound dose-rate effect is observed over the
      dose-rate range of 6 to 20 cGy/h. An inverse dose-rate effect was observed for
      both radionuclides, with its onset occurring at a dose rate of about 20-30 cGy/h.
      The average RBE of 103Pd relative to 125I was determined to be 1.45 +/- 0.07,
      1.41 +/- 0.07, 0.70 +/- 0.07 and 1.49 +/- 0.07 at dose rates of 6.9, 12.6, 19.0
      and 26.7 cGy/h, respectively. Because 103Pd implants are generally prescribed at
      a higher initial dose rate (21 cGy/h) than the corresponding 125I implants (7
      cGy/h), the effects of both dose rate and photon energy on biological response
      must be considered together. For the CCL-16 cells, the RBE of 103Pd at 19.0 cGy/h
      relative to that of 125I at 6.9 cGy/h was estimated to be 2.3 +/- 0.5.

PMID- 15850412
TI  - Measurement of the initial levels of DNA damage in human lymphocytes induced by
      29 kV X rays (mammography X rays) relative to 220 kV X rays and gamma rays.
AB  - Experiments using the alkaline comet assay, which measures all single-strand
      breaks regardless of their origin, were performed to evaluate the biological
      effectiveness of photons with different energies in causing these breaks. The aim
      was to measure human lymphocytes directly for DNA damage and subsequent repair
      kinetics induced by mammography 29 kV X rays relative to 220 kV X rays, 137Cs
      gamma rays and 60Co gamma rays. The level of DNA damage, predominantly due to
      single-strand breaks, was computed as the Olive tail moment or percentage DNA in
      the tail for different air kerma doses (0.5, 0.75, 1, 1.5, 2 and 3 Gy). Fifty
      cells were analyzed per slide with a semiautomatic imaging system. Data from five
      independent experiments were transformed to natural logarithms and fitted using a
      multiple linear regression analysis. Irradiations with the different photon
      energies were performed simultaneously for each experiment to minimize
      interexperimental variation. Blood from only one male and one female was used.
      The interexperimental variation and the influence of donor gender were
      negligible. In addition, repair kinetics and residual DNA damage after exposure
      to a dose of 3 Gy were evaluated in three independent experiments for different
      repair times (10, 20, 30 and 60 min). Data for the fraction of remaining damage
      were fitted to the simple function F(d) = A/(t + A), where F(d) is the fraction
      of remaining damage, t is the time allowed for repair, and A (the only fit
      parameter) is the repair half-time. It was found that the comet assay data did
      not indicate any difference in the initial radiation damage produced by 29 kV X
      rays relative to the reference radiation types, 220 kV X rays and the gamma rays
      of 137Cs and 60Co, either for the total dose range or in the low-dose range.
      These results are, with some restrictions, consistent with physical examinations
      and predictions concerning, for example, the assessment of the possible
      difference in effectiveness in causing strand breaks between mammography X rays
      and conventional (150-250 kV) X rays, indicating that differences in biological
      effects must arise through downstream processing of the damage.

PMID- 15850413
TI  - Comparative radiation tolerance based on the induction of DNA double-strand
      breaks in tobacco BY-2 cells and CHO-K1 cells irradiated with gamma rays.
AB  - Higher plants are generally more tolerant to ionizing radiation than mammals. To
      explore the radiation tolerance of higher plants, the induction of DNA double
      strand breaks (DSBs) by gamma rays was investigated in tobacco BY-2 cells and
      compared with that in Chinese hamster ovary (CHO)-K1 cells as a reference. This
      is the first examination of radiation-induced DSBs in a higher plant cell. The
      resulting DNA fragments were separated by pulsed-field gel electrophoresis and
      stained with SYBR Green I. The initial yield of DSBs was then quantified from the
      fraction of DNA fragments shorter than 1.6 Mbp based on the assumption of random
      distribution of DSBs. The DSB yield in tobacco BY-2 cells (2.0 +/- 0.1 DSBs Gbp(
      1) Gy(-1)) was only one-third of that in CHO-K1 cells. Furthermore, the
      calculated number of DSBs per diploid cell irradiated with gamma rays at the mean
      lethal dose was five times greater in BY-2 cells (263 +/- 13) than in CHO-K1
      cells. These results suggest that the radiation tolerance of BY-2 cells appears
      to be due not only to a lower induction of DNA damage but also to a more
      efficient repair of the induced DNA damage.

PMID- 15850414
TI  - Dose-dependent misrejoining of radiation-induced DNA double-strand breaks in
      human fibroblasts: experimental and theoretical study for high- and low-LET
      radiation.
AB  - Misrejoining of DNA double-strand breaks (DSBs) was measured in human primary
      fibroblasts after exposure to X rays and high-LET particles (helium, nitrogen and
      iron) in the dose range 10-80 Gy. To measure joining of wrong DNA ends, the
      integrity of a 3.2-Mbp restriction fragment was analyzed directly after exposure
      and after 16 h of repair incubation. It was found that the misrejoining frequency
      for X rays was nonlinearly related to dose, with less probability of misrejoining
      at low doses than at high doses. The dose dependence for the high-LET particles,
      on the other hand, was closer to being linear, with misrejoining frequencies
      higher than for X rays, particularly at the lower doses. These experimental
      results were simulated with a Monte Carlo approach that includes a cell nucleus
      model with all 46 chromosomes present, combined with realistic track structure
      simulations to calculate the geometrical positions of all DSBs induced for each
      dose. The model assumes that the main determinant for misrejoining probability is
      the distance between two simultaneously present DSBs. With a Gaussian interaction
      probability function with distance, it was found that the data for both low- and
      high-LET radiation could be fitted with an interaction distance (sigma of the
      Gaussian curve) of 0.25 microm. This is half the distance previously found to
      best fit chromosomal aberration data in human lymphocytes using the same methods
      (Holley et al., Radiat. Res. 158, 568-580, 2002). The discrepancy may indicate
      inadequacies in the chromosome model, for example insufficient chromosomal
      overlap, but may also be partly due to differences between fibroblasts and
      lymphocytes.

PMID- 15850415
TI  - Synchrotron radiation-induced formation and reactions of free radicals in human
      acellular dermal matrix.
AB  - The present work characterizes the formation of free radicals in an implantable
      human acellular dermal tissue (Alloderm, LifeCell Corp., Branchburg, NJ) upon
      irradiation. The tissue was preserved in a vitreous carbohydrate matrix by freeze
      drying. Freeze-dried samples were irradiated using a synchrotron light source,
      and free radicals generated were investigated using the electron paramagnetic
      resonance (EPR) technique. At least two free radical populations, with g factors
      of 1.993 (approximately 43%) and 2.002 (approximately 57%), respectively, were
      identified in the irradiated tissue. The transformation (reaction) kinetics of
      free radicals produced was investigated in the presence of nitrogen, oxygen and
      moisture. The reaction kinetics of free radicals was extremely slow in the
      nitrogen environment. The presence of oxygen and moisture greatly accelerated
      free radical reactions in the tissue matrix. The reaction of free radicals could
      not be described by traditional reaction kinetics. A dispersive kinetics model
      and a diffusion model were developed to analyze the reaction kinetics in the
      present study. The dispersive model took into consideration molecular mobility
      and dispersivity of free radicals in the heterogeneous tissue material. The
      diffusion model described the radical reaction kinetics as two parallel and
      simultaneous processes: a first-order fast kinetics mainly on tissue surface and
      a diffusion-limited slow kinetics in deeper layers of the tissue matrix. Both
      models described quantitative experimental data well. Further investigation is
      needed to verify whether any of these two models or concepts describes the
      inherent radical reaction kinetics in the solid tissue matrix.

PMID- 15850416
TI  - Radiation-induced up-regulation of adhesion molecules in brain microvasculature
      and their modulation by dexamethasone.
AB  - Little is known about the time course and magnitude of the up-regulation of
      endothelial cell adhesion molecules (ECAMs) in irradiated brain vasculature and
      the mechanisms by which dexamethasone modulates this up-regulation. We used
      antibody-conjugated microspheres and a rat closed cranial window model to
      determine the time course of functional up-regulation of radiation (20 Gy)
      induced ICAM1, E-selectin and P-selectin in the pial vasculature of the rat brain
      and to determine the relationship between suppression of inflammation by
      dexamethasone and the expression of these ECAMs. The results indicate that ICAM1,
      E-selectin and P-selectin were up-regulated to a functional level in the
      microvasculature with distinct time-course patterns. The number of adherent anti
      E-selectin and anti-P-selectin microspheres was 5- 12 times greater than that of
      IgG microspheres 3-6 h postirradiation, and their expression returned to normal
      at 48 h. The number of adherent anti-ICAM1 microspheres was five and nine times
      greater than that of IgG at 24 and 48 h, respectively, and returned to baseline
      by 7 days. Dexamethasone significantly reduced the number of adhering leukocytes
      and the number of adhering anti-ICAM1, anti-E-selectin and anti-P-selectin
      microspheres to background levels. Our findings partially identify a key sequence
      in radiation-induced inflammatory response and provide a potential means to limit
      radiation-induced inflammatory responses and their potential side effects in the
      brain.

PMID- 15850417
TI  - Direct single gene mutational events account for radiation-induced intestinal
      adenoma yields in Apc(Min/+) mice.
AB  - Data on the induction of small intestinal tumors, predominantly adenomas, by X
      radiation in Apc(Min/+) mice are reported. Comparison of these incidences with
      estimates of radiation-induced direct single gene mutation frequencies taken from
      the literature support the hypothesis that direct mutational loss of Apc+ is the
      sole requirement for initiation of adenoma. Furthermore, estimates of radiation
      induced initiation of adenoma per target stem cell in this animal model are
      similar to or less than radiation-induced direct somatic gene mutation
      frequencies. Therefore, while the data reported here do not preclude a role for
      genomic instability in tumor progression, it is not necessary in this model to
      postulate the involvement of radiation-induced transmissible genomic instability
      in initiation of intestinal adenoma.

PMID- 15850418
TI  - Application of autologous hematopoietic cell therapy to a nonhuman primate model
      of heterogeneous high-dose irradiation.
AB  - We developed a model of heterogeneous irradiation in a nonhuman primate to test
      the feasibility of autologous hematopoietic cell therapy for the treatment of
      radiation accident victims. Animals were irradiated either with 8 Gy to the body
      with the right arm shielded to obtain 3.4 Gy irradiation or with 10 Gy total body
      and 4.4 Gy to the arm. Bone marrow mononuclear cells were harvested either before
      irradiation or after irradiation from an underexposed area of the arm and were
      expanded in previously defined culture conditions. We showed that hematopoietic
      cells harvested after irradiation were able to expand and to engraft when
      reinjected 7 days after irradiation. Recovery was observed in all 8-Gy-irradiated
      animals, and evidence for a partial recovery was observed in 10-Gy-irradiated
      animals. However, in 10-Gy-irradiated animals, digestive disease was observed
      from day 16 and resulted in the death of two animals. Immunohistological
      examinations showed damage to the intestine, lungs, liver and kidneys and
      suggested radiation damage to endothelial cells. Overall, our results provide
      evidence that such an in vivo model of heterogeneous irradiation may be
      representative of accidental radiation exposures and may help to define the
      efficacy of therapeutic interventions such as autologous cell therapy in
      radiation accident victims.

PMID- 15850419
TI  - Adjusting lung cancer risks for temporal and spatial variations in radon
      concentration in dwellings in Gansu Province, China.
AB  - Our recent study in Gansu Province, China reported an increasing risk of lung
      cancer with increasing residential radon concentration that was consistent with
      previous pooled analyses and with meta-analyses of other residential studies
      (Wang et al., Am. J. Epidemiol. 155, 554-564, 2002). Dosimetry used current radon
      measurements (1-year track-etch detectors) in homes to characterize
      concentrations for the previous 30 years, resulting in uncertainties in exposure
      and possibly reduced estimates of disease risk. We conducted a 3-year substudy in
      55 houses to model the temporal and spatial variability in radon levels and to
      adjust estimates of radon risk. Temporal variation represented the single largest
      source of uncertainty, suggesting the usefulness of multi-year measurements to
      assess this variation; however, substantial residual variation remained
      unexplained. The uncertainty adjustment increased estimates of the excess odds
      ratio by 50-100%, suggesting that residential radon studies using similar
      dosimetry may also underestimate radon effects. These results have important
      implications for risk assessment.

PMID- 15850420
TI  - Simulation of exposure and SAR estimation for adult and child heads exposed to
      radiofrequency energy from portable communication devices.
AB  - The level and distribution of radiofrequency energy absorbed in a child's head
      during the use of a mobile phone compared to those in an adult head has been a
      controversial issue in recent years. It has been suggested that existing methods
      that are used to determine specific absorption rate (SAR) and assess compliance
      with exposure standards using an adult head model may not adequately account for
      potentially higher levels of exposure in children due to their smaller head size.
      The present study incorporates FDTD computations of locally averaged SAR in two
      different anatomically correct adult and child head models using the IEEE
      standard (Std. C95.3-2002) SAR averaging algorithm. The child head models were
      obtained by linear scaling of the adult head model to replicate the conditions of
      previous studies reported in the literature and also by transforming the
      different adult head models based on data on the external shapes of children's
      heads. The tissue properties of the adult and corresponding child head models
      were kept the same. In addition, modeling and experimental measurements were made
      using three spheres filled with a tissue-equivalent mixture to approximate heads
      of increasing size. Results show that the peak local average SAR over 1 g and 10
      g of tissue and the electromagnetic energy penetration depths are about the same
      in all of the head models under the same exposure conditions. When making
      interlaboratory comparisons, the model and the SAR averaging algorithm used must
      be standardized to minimize controversy.

PMID- 15850421
TI  - Sugar radicals in DNA: isolation of neutral radicals in gamma-irradiated DNA by
      hole and electron scavenging.
AB  - In this investigation of the radical formation and the reaction of radicals in
      gamma-irradiated DNA, we report the isolation of putative neutral radicals by the
      scavenging of holes by Fe(CN)6(4-) and of electrons by Fe(CN)6(3-). Experiments
      are performed under conditions that emphasize direct and quasi-direct effects
      (collectively called direct-type effects.) Samples containing Fe(CN)6(4-) show
      effective scavenging of holes and the ESR spectra obtained arise principally from
      DNA anion radicals and neutral radicals. On the other hand, for samples
      containing Fe(CN)6(3-), electron scavenging is highly efficient, and the
      resulting spectra arise principally from guanine cation radicals and neutral
      radicals. When both Fe(CN)6(4-) and Fe(CN)6(3-) are present, a near complete
      scavenging of cation radicals and anion radicals is observed at 77 K, and the ESR
      spectra that result originate predominantly with neutral radicals which are
      assigned predominantly to radicals on the sugar phosphate backbone. A notable
      finding is the presence of spectral components that indicate the formation,
      through the rupture of the C3'-O bond, of a neutral deoxyribose radical; a
      concurrent strand break must accompany formation of this radical. This radical
      was previously reported in argon-ion-irradiated DNA and now, for the first time,
      is reported in DNA irradiated with low-LET radiation.

PMID- 15850422
TI  - Standard ultraviolet daylight for nonextreme exposure conditions.
AB  - The skin is exposed to ultraviolet radiation (UVR) from natural or artificial
      sources on a daily basis. The effects of chronic low dose exposure merit
      investigation, even when these effects are neither conspicuous nor clinically
      assessable. The purpose of the present study was to define a relative spectral UV
      irradiance that is representative of frequent nonextreme sun exposure conditions
      and therefore more appropriate for studies of the long-term and daily effects of
      solar UV on the skin. Solar spectral UV irradiance values were calculated for
      different dates and locations by using a radiative transfer model. The spectral
      irradiance values obtained when the solar elevation is lower than 45 degrees were
      averaged. An important feature is the dUVA (320-400 nm) to dUVB (290-320 nm)
      irradiance values ratio, which was found to be 27.3 for the overall average. When
      the months corresponding to extreme irradiance values (low or high) were excluded
      from the calculations, the dUVA to dUVB ratio ranged from 27.2 to 27.5. The mean
      spectral irradiance of the model presented here represents environmental UV
      exposure conditions and can be used both as a standard to investigate the
      biological effects of a nonextreme UVR and to assess the effectiveness of
      products for daily skin protection.

PMID- 15850423
TI  - Sun-reactive Skin Type in 4912 French adults participating in the SU.VI.MAX
      study.
AB  - Phototype classifications were initially developed in an attempt to predict the
      skin reactions of patients to phototherapy and are now widely used to advise
      individuals with regard to sun protection. A transversal study was conducted on
      the SU.VI.MAX cohort to estimate the frequency of sun-reactive skin features in a
      large, general adult population-based sample, and to describe the associations
      between these features. The data were collected 3 years after the beginning of
      the SU.VI.MAX nutritional intervention study on 4912 volunteers (2868 women aged
      35-60 years and 2044 men aged 45-60 years). A multiple correspondence analysis
      was performed to study the associations between the features. The results showed
      that these features correspond to a one-dimensional phenomenon, which allowed us
      to establish a score to summarize skin sensitivity to sun exposure. Furthermore,
      we found a link between gender and phototype using the Cesarini classification
      (phototype > or = IV: 37% of women, 47% of men). The analysis of the relationship
      with sun-reactive skin features and the score revealed the same trend. Phenotypic
      evaluation appears to be a good estimator of skin sensitivity to sun exposure for
      clinical screening or for use in research, and is easy to collect at a lower
      cost. Moreover, the sun sensitivity difference between gender should be
      considered in education about photoprotection.

PMID- 15850424
TI  - Miniature personal electronic UVR dosimeter with erythema response and time
      stamped readings in a wristwatch.
AB  - Personal ultraviolet radiation (UVR) dosimetry is important because sunlight is
      the most important risk factor for skin cancer and a risk factor for some eye
      diseases and immunosuppression and related disorders. Integrating devices, such
      as polysulphone film dosimeters, are generally used. To measure the exact dose at
      specific times, we have developed a personal electronic UVR dosimeter that makes
      time-stamped measurements. It has a sensor with an erythema action spectrum
      response and a linear sensitivity (dose-response) with no offset. The sensor has
      cosine response, and the dosimeter can cope with environmental conditions such as
      rain, temperature and dirt. It can be programmed to measure with different time
      intervals and save the average of a specified number of measurements in the
      memory that can store 32 000 time-stamped measurements. It is small (36 x 28 x 13
      mm), weighs 14 g and can work for 4 months without maintenance. It is worn on the
      wrist, is equipped with a watch showing the time and may thus be used in large
      scale studies. The sensitivity can change by 10% due to temperature changes from 
      5 to 40 degrees C. The UVR dosimeter sensitivity is 0.09 standard erythema doses
      (SED)/h and the difference in total received dose during 7 days between a Solar
      Light 501 UV-Biometer (186 SED) and our UVR dosimeter was 3% and the median
      difference in daily total dose was 2.2%. The dosimeter provides unique
      possibilities. Examples of personal UVR measurements, data calculations and how
      they can be interpreted are given.

PMID- 15850425
TI  - Photophysical properties of crowned porphyrins.
AB  - In this study, we evaluated the photophysical properties of 5,10,15,20-tetrakis[4
      (1,4,7,10,13-pentaoxacyclopentadecane-2-aminomethyl)2,3,5,6-(tetrafluoro)-phenyl]
      porphyrin (H2C4P) and Zn(II)5,10,15,20-tetrakis[4-(1,4,7,10,13-pentaoxacyclopenta
      decane-2-aminomethyl)2,3,5,6-(tetrafluoro)-phenyl]-porphyrinate (ZnC4P). We
      observed that these porphyrins have unique properties when compared with
      classical porphyrins. The porphyrins H2C4P and ZnC4P showed efficient transfer
      energy S1 to T1 by intersystem crossing with high and reasonable yields of
      triplet excited state and singlet oxygen production. These amphiphilic structures
      of these porphyrins could improve its localization in the tumor cells due to the
      presence of the crown ether in its framework. We also believed that the crown
      ether could modulate the change in ion homeostase (Ca(+2), K+, Na+) as already
      described by some new phthalocyanine dye. This fact makes us believe that it
      could be reasonably used as a photosensitizer for PDT purposes.

PMID- 15850426
TI  - Monitoring cell survival after extraction of a single subcellular organelle using
      optical trapping and pulsed-nitrogen laser ablation.
AB  - This paper characterizes cell viability in three different cell lines--Chinese
      hamster ovary cells (CHO), neuroblastoma cells fused with glialoma cells (NG108
      15) and murine embryonic stem cells (ES-D3)--after N2 laser disruption of the
      cell membrane and removal, via optical trapping, of a single subcellular
      organelle. Morphological changes and viability (as determined by live/dead
      fluorescent stains) of the cell were monitored every half hour over a 4-h period
      postsurgery. The ability of the cell to survive organelle extraction was found to
      depend both on the conditions under which surgery was performed and on the cell
      type. The average viability after surgery for CHO cells was approximately 80%,
      for NG 108 cells it was approximately 30% and for ES-D3 cells postsurgery
      viability was approximately 10%. From over 600 surgeries we found the survival of
      the cell is determined almost exclusively within the first hour postsurgery
      regardless of cell line. The optimal pulse energy for N2 laser ablation was
      approximately 0.7 microJ. The N2 pulse produced an approximately 1-3 microm hole
      in the cell membrane and proved to be the primary source of cell death in those
      cells that did not survive the procedure.

PMID- 15850428
TI  - The crisis in mental health: the chariot needs one horseman.
AB  - Better coordination costs no more and improves the lot of patients.

PMID- 15850429
TI  - Smoothing the transition to adult care.
AB  - The most important need is for a change of attitude and approach.

PMID- 15850430
TI  - Physical examination: bewitched, bothered and bewildered.
AB  - Next to nothing is known about physical findings' impact on patient care.

PMID- 15850431
TI  - Cost-effectiveness of drug-eluting stents: if only all things were equal.
AB  - They reduce rates of restenosis but not mortality or infarction--so are they
      worth it?

PMID- 15850432
TI  - Depressed youth, suicidality and antidepressants.
AB  - No cause for panic, but an incentive to improve clinical practice.

PMID- 15850433
TI  - Young adults in children's hospitals: why are they there?
AB  - OBJECTIVE: To measure the pattern of admissions of young adults to a children's
      hospital. DESIGN AND SETTING: Ten-year audit (1992-2001) of admissions of young
      adults aged 18 years and over to the Royal Children's Hospital (RCH), Melbourne,
      with a detailed chart review of the 2001 cohort to assess disease complexity and
      transition planning. OUTCOME MEASURES: Number of admissions, disease complexity,
      transition planning. RESULTS: There was a significant increase in the number of
      young adults admitted over 10 years, from 308 in 1992-1993 to 659 in 2000-2001.
      The greatest increase was in admissions to surgical units. There was significant
      variation in admission practices between units over time. Many young adults
      required multidisciplinary care: 57% had more than three medical/surgical units
      involved in their care, and 34% had two or more allied health units involved.
      Fifty-one per cent of surgical inpatients and 28% of medical inpatients had no
      documented plan for transition to adult care. Only 30% of medical and 17% of
      surgical inpatients in 2001 had been transferred to adult services by 2002.
      CONCLUSIONS: Both disease complexity and failure of transition planning appear to
      have contributed to the increased admission of young adults to the RCH. While
      greater support of transition planning is needed, there are also concerns about
      the lack of appropriate services within the adult sector for young adults with
      complex, multidisciplinary healthcare needs.

PMID- 15850434
TI  - Men's reactions to disclosed and undisclosed opportunistic PSA screening for
      prostate cancer.
AB  - OBJECTIVE: To assess the degree to which men considered it appropriate for
      general practitioners to order prostate-specific antigen (PSA) testing if the
      testing was either "disclosed" or "undisclosed" to the patient. DESIGN: Telephone
      administered survey conducted in June to October 2000. PARTICIPANTS: 514 men aged
      50-70 years, identified by random selection of households from the Sydney
      Electronic White Pages phone directory. METHODS: We developed two hypothetical
      scenarios. Each scenario described a GP ordering a PSA test for a male patient at
      the same time as other pathology tests were ordered. In Scenario 1, the GP's
      intention to order a PSA test was disclosed to the patient ("disclosed"). In
      Scenario 2, the GP did not tell the patient a PSA test was being ordered
      ("undisclosed"). For each scenario, men reported the degree to which they
      perceived screening to be "appropriate". We also recorded demographic
      characteristics, health status and health locus of control, and administered a 14
      question knowledge test about prostate cancer and PSA screening. RESULTS: Over
      90% of men stated that "disclosed" PSA screening was either "appropriate" or
      "very appropriate". Significantly fewer (44.9%) rated "undisclosed" screening as
      appropriate/very appropriate (P < 0.001). While the skewed distribution of
      responses to Scenario 1 precluded multivariate analysis to determine predictors,
      men rejecting "undisclosed" PSA screening (Scenario 2) were more likely to be
      younger (adjusted odds ratio [AOR], 0.97; 95% CI, 0.94-1.00; P = 0.03); to have
      better knowledge of the issues (AOR, 1.01; 95% CI, 1.00-1.03; P = 0.02); and to
      be single (AOR, 0.62; 95% CI, 0.41-0.94; P = 0.02). CONCLUSIONS: Many men
      consider that inclusion of PSA screening within a battery of pathology tests
      without disclosure to the patient is unacceptable. Educating men about the pros
      and cons of screening may alter their support of opportunistic screening and thus
      enhance community expectations of "informed participation".

PMID- 15850435
TI  - Bound for Sydney town: health surveillance on international cruise vessels
      visiting the Port of Sydney.
AB  - A program for routine health surveillance on international cruise ships visiting
      the Port of Sydney has been developed since 1998. Before introduction of this
      program, ships only reported quarantinable diseases and were not aware of the
      Australian requirement to report other infectious diseases. Voluntary routine
      reporting, developed in partnership with the cruise ship industry, provides
      timely information on all infectious diseases of public health interest during
      every cruise. During 1999-2003, the program resulted in detection of and response
      to 14 outbreaks of gastroenteritis or acute respiratory infection, affecting more
      than 1400 passengers and crew. The program has improved preventive action, and
      risk communication and management by cruise ship operators, and led to more
      timely investigation and support by public health authorities.

PMID- 15850436
TI  - Ten years of mental health service reform in Australia: are we getting it right?
AB  - We summarise the most recent data available on changes to the public and private
      mental health sectors from the commencement of the National Mental Health
      Strategy in 1993 to 2002. There has been substantial service system change in the
      directions agreed by governments under the Strategy, supported by a 65% growth in
      government spending on mental health. Despite this there is growing public and
      professional concern about deficiencies in the mental health service system. We
      review the current call for change in light of increased community expectations
      and growth in demand for services. Given broad national and international support
      for Australia's policy directions, the problems lie with the pace and extent of
      change and ensuring better outcomes from the increased investment in mental
      health care.

PMID- 15850437
TI  - Australian mental health reform: time for real outcomes.
AB  - After 12 years of national mental health reform, major service gaps and poor
      experiences of care are common. The mental health community reports little
      progress in implementing its key priorities, such as expanded early-intervention
      programs, comanagement of people with mental health problems and related alcohol
      or substance misuse, and widening of the spectrum of acute care settings. We
      propose new national targets for reducing the social and economic costs of poor
      mental health; these include increased access to effective care, reduced suicide
      rates and improved rates of return to full social and economic participation. We
      detail specific service reforms designed to maximise the chance of achieving
      these targets, and prioritise youth health and integrated primary care programs.
      New independent and national reporting systems on the progress of mental health
      reform are urgently required.

PMID- 15850438
TI  - Funnel-web spider bite: a systematic review of recorded clinical cases.
AB  - OBJECTIVE: To investigate species-specific envenoming rates and spectrum of
      severity of funnel-web spider bites, and the efficacy and adverse effects of
      funnel-web spider antivenom. DATA SOURCES: Cases were identified from a
      prospective study of spider bite presenting to four major hospitals and three
      state poisons information centres (1999-2003); museum records of spider specimens
      since 1926; NSW Poisons Information Centre database; MEDLINE and EMBASE search;
      clinical toxinology textbooks; the media; and the manufacturer's reports of
      antivenom use. DATA EXTRACTION: Patient age and sex, geographical location,
      month, expert identification of the spider, clinical effects and management;
      envenoming was classified as severe, mild-moderate or minor/local effects. DATA
      SYNTHESIS: 198 potential funnel-web spider bites were identified: 138 were
      definite (spider expertly identified to species or genus), and 77 produced severe
      envenoming. All species-identified severe cases were attributed to one of six
      species restricted to NSW and southern Queensland. Rates of severe envenoming
      were: Hadronyche cerberea (75%), H. formidabilis (63%), Atrax robustus (17%),
      Hadronyche sp. 14 (17%), H. infensa (14%) and H. versuta (11%). Antivenom was
      used in 75 patients, including 22 children (median dose, 3 ampoules; range, 1
      17), with a complete response in 97% of expertly identified cases. Three adverse
      reactions were reported, all in adults: two early allergic reactions (one mild
      and one with severe systemic effects requiring adrenaline), and one case of serum
      sickness. CONCLUSIONS: Severe funnel-web spider envenoming is confined to NSW and
      southern Queensland; tree-dwelling funnel webs (H. cerberea and H. formidabilis)
      have the highest envenoming rates. Funnel-web spider antivenom appears effective
      and safe; severe allergic reactions are uncommon.

PMID- 15850439
TI  - Bisphosphonates and avascular necrosis of the jaw: a possible association.

PMID- 15850440
TI  - Bisphosphonates and osteonecrosis of the jaw.

PMID- 15850441
TI  - 8. Investigation and treatment of upper-airway obstruction: childhood sleep
      disorders I.
AB  - Always take a history of snoring and sleep disturbance when reviewing children in
      primary care, as there is evidence that episodes of hypoxia and arousal during
      sleep may result in deficits in memory, attention and behaviour, in addition to
      the well known sequelae of growth failure, developmental delay and cor pulmonale.
      Check for changes in behaviour affecting school progress. To investigate for
      possible obstructive sleep apnoea syndrome (OSAS), clinical examination, lateral
      neck x-ray (adenoidal hypertrophy) and overnight oximetry (desaturation episodes)
      are useful screening tests, but oximetry is best used in conjunction with
      polysomnography. A negative oximetry test does not exclude OSAS. Polysomnography
      is the best method for detecting and assessing the severity of OSAS in children,
      and is especially helpful for prioritising treatment and evaluating the risk of
      perioperative complications of adenotonsillectomy. Adenotonsillectomy is thought
      to "cure" (ie, symptoms disappear and overnight respiratory parameters are
      corrected) in about 80% of children with OSAS. The remaining 20% need ongoing
      evaluation and treatment. Further research is needed to determine the "true"
      prevalence of OSAS; what degrees of severity of upper-airway obstruction lead to
      morbidity requiring treatment; and whether the deficits in neurocognitive
      function associated with sleep-disordered breathing are fully correctable.

PMID- 15850442
TI  - Randomised trial of intranasal versus intramuscular naloxone in prehospital
      treatment for suspected opioid overdose.

PMID- 15850443
TI  - Fungal endophthalmitis in intravenous drug users injecting buprenorphine
      contaminated with oral Candida species.

PMID- 15850444
TI  - The Nobel Prize and mainstream medicine.

PMID- 15850445
TI  - Evidence-based policy making?

PMID- 15850446
TI  - Medical humanities: to cure sometimes, to relieve often, to comfort always.

PMID- 15850447
TI  - Continuous improvement and "Continuous Improvement".

PMID- 15850449
TI  - The alpha-glucanase Agn1p is required for cell separation in Schizosaccharomyces
      pombe.
AB  - BACKGROUND INFORMATION: In animal cells, cytokinesis occurs by constriction of an
      actomyosin ring. In fission yeast, ring constriction is followed by deposition of
      a multilayered division septum that must be cleaved to release the two daughter
      cells. Although many studies have focused on the actomyosin ring and septum
      assembly, little is known about the later steps involving the cleavage of the
      cell wall. RESULTS: We identified a novel gene in Schizosaccharomyces pombe,
      namely the agn1(+) gene that has homology to fungal 1,3-alpha-glucanases
      (mutanases). Disruption of the agn1(+) gene is not lethal to the cells, but does
      interfere with their separation, whereas overexpression of Agn1p is toxic and
      causes cell lysis. Agn1p levels reach a peak during septation and the protein
      localizes to the septum region before cell separation. Moreover, agn1(+) is
      responsible for the 1,3-alpha-glucanase activity, which shows a maximum at the
      end of septation. CONCLUSIONS: Our results clearly suggest the existence of a
      relationship between agn1(+), 1,3-alpha-glucanase activity and the completion of
      septation in S. pombe. Agn1p could be involved in the cleavage of the cylinder of
      the old wall that surrounds the primary septum, a region rich in alpha-glucans.

PMID- 15850448
TI  - Aquaporin-1 and -9 are differentially regulated by oestrogen in the efferent
      ductule epithelium and initial segment of the epididymis.
AB  - BACKGROUND INFORMATION: Efferent ductules reabsorb more than 90% of the rete
      testis fluid, a process that involves ion transporters and AQP (aquaporin) water
      channels. Oestrogen has been shown to modulate the expression of the ion
      transporters involved in this activity, but reports of AQP regulation in the male
      tract have been confounding. To understand better the regulation of AQP1 and
      AQP9, we investigated their expression in rat efferent ductules and initial
      segment of the epididymis after treatment with the pure antioestrogen ICI 182,780
      or bilateral efferent duct ligation, or castration, followed by hormone
      replacement. RESULTS: Results show that AQP9 is modulated by oestrogen in the
      efferent ductule epithelium, but not in the initial segment of the epididymis.
      DHT (5alpha-dihydrotestosterone) also modulated AQP9 in efferent ductules. AQP9
      was down-regulated by the antioestrogen in efferent ductules on day 45 post
      treatment, which occurred before the non-ciliated cells had shown significant
      loss of microvilli. DHT, but not oestradiol, modulated AQP9 expression in the
      initial segment of the epididymis. In contrast, testosterone, DHT, oestrogen or
      the antioestrogen did not alter AQP1 staining, indicating constitutive expression
      of AQP1 in the efferent ductule epithelium. AQP1 expression was induced in
      peritubular cells of efferent ductules and in the initial segment of the
      epididymis after castration and long-term treatment with the antioestrogen.
      Although peritubular AQP1 staining in efferent ductules was partially reversed by
      the androgens, it was not reversed after any treatment in the initial segment of
      the epididymis. CONCLUSIONS: These results demonstrate that efferent ductules are
      unique in requiring both oestrogen and androgen to regulate an important mediator
      of fluid reabsorption, whereas the initial segment is dependent only on androgen
      stimulation.

PMID- 15850450
TI  - Neuropeptide Y expression, localization and cellular transducing effects in
      HUVEC.
AB  - BACKGROUND INFORMATION: NPY (neuropeptide Y) may have an effect on the properties
      of vascular endothelial cells such as pro-angiogenic effects and potentiation of
      noradrenaline-induced vasoconstriction. In HUVEC (human umbilical-vein
      endothelial cells), immunoreactive neuropeptide Y has been detected, but NPY
      synthesis, storage and secretion have not been studied. The aim of the present
      study was to establish NPY expression, storage and cellular transducing effects
      in HUVEC. RESULTS: HUVEC contain 0.19 fmol of NPY/microg of protein and 0.46 fmol
      of pro-NPY/microg of protein, as measured by ELISA. RT (reverse transcriptase)
      PCR confirmed the expression of NPY in HUVEC. Immunofluorescence revealed the
      presence of NPY in small punctate structures, with a fluorescence pattern
      different from that observed for von Willebrand factor, indicating distinct
      storage compartments. Double labelling for NPY and Rab3A demonstrated similar
      granular patterns, with at least partial co-localization. Electron microscopy
      showed NPY immunoreactivity in vesicle-like cytoplasmic structures, of a fine
      fibrillar texture, as well as in mitochondria and in the nucleus. A similar
      general distribution pattern was also obtained for Rab3A. Y1 and Y2 receptors
      were expressed in HUVEC as assessed by RT-PCR, and they were functional since NPY
      induced a 42 nM intracellular calcium increase within 100 s, representing 22% of
      the histamine-induced response. In contrast with histamine, NPY did not induce
      acute von Willebrand factor secretion. CONCLUSIONS: HUVEC produce, store and
      respond to NPY, suggesting an autocrine regulatory role for NPY in the
      endothelium.

PMID- 15850451
TI  - Heat-shock response down-regulates interleukin-18 expression in murine peritoneal
      macrophages.
AB  - BACKGROUND INFORMATION: The heat-shock response is a self-defence mechanism that
      protects cells and organisms from a wide range of harmful stresses. Recent
      studies revealed that it involved the regulation of cytokine expression.
      Interleukin-18 (IL-18) is an important cytokine in mediating immune response.
      RESULTS: We studied interferon-gamma (IFN-gamma)-induced IL-18 expression in heat
      shock-treated murine peritoneal macrophages. Our results showed that the heat
      shock response significantly inhibited the expression of IFN-gamma-induced pro
      inflammatory cytokine IL-18. Interferon consensus sequence binding protein
      (ICSBP) is a transcription factor that binds to the promoter of IL-18 and
      regulates the transcription of IL-18. Further research on the down-regulation
      mechanism showed that the DNA-binding activity of ICSBP was greatly reduced by
      the heat shock response. CONCLUSIONS: These results suggest that the inhibitory
      effect of heat-shock response on IL-18 production in IFN-gamma-stimulated
      macrophages is related to the suppression of the binding activity of ICSBP.

PMID- 15850452
TI  - Cloning and expression of three aquaporin homologues from the European eel
      (Anguilla anguilla): effects of seawater acclimation and cortisol treatment on
      renal expression.
AB  - BACKGROUND INFORMATION: The European eel (Anguilla anguilla) is able to
      osmoregulate over a wide range of environmental salinities from FW (freshwater)
      to hyperconcentrated SW (seawater). Successful acclimation is associated with
      strict regulation of ion and water transport pathways within key osmoregulatory
      epithelia to enable animals to survive the dehydrating or oedematous conditions.
      These observations suggested that homologues of the AQP (aquaporin) water channel
      family were expressed in the eel and that these proteins may contribute to the
      water transport and osmoregulation in all euryhaline teleosts. RESULTS:
      Complementary DNAs encoding a homologue of the mammalian aquaglyceroporins
      (termed AQPe) and two homologues of mammalian aquaporin-1 [termed AQP1 and
      AQP1dup (aquaporin-1 duplicate)] were isolated from the European eel. Northern
      blot analysis revealed (i) two AQP1 transcripts exhibiting a wide tissue
      distribution, (ii) a single AQP1dup mRNA transcript found in the kidney and the
      oesophagus, and (iii) a single AQPe mRNA detectable mainly in the kidney and the
      intestine. The relative expression of isoforms within the kidney was
      AQP1dup>AQPe>AQP1. SW acclimation significantly reduced the abundance of AQP1,
      AQP1dup and AQPe transcripts in the kidney of yellow eels by approx. 72, 66 and
      34% respectively, whereas the expression levels in silver eels were independent
      of salinity and equivalent to those observed in yellow SW-acclimated fish. AQP1
      protein expression was primarily located within the vascular endothelium in
      yellow eels and the epithelial apical brush border in some renal tubules in
      silver eels. Infusion of cortisol into FW eels had no effect on AQPe mRNA
      expression, but induced significant decreases in AQP1 and AQP1dup mRNA levels in
      the kidney of yellow eels. Cortisol infusion had no effect on the expression of
      any isoform in the silver eels. CONCLUSIONS: These results suggest that SW
      acclimation or cortisol infusion induces a down-regulation of renal AQP
      expression in yellow eels. However, the lower levels of aquaporin expression
      found within the silver eel kidney were not further reduced by salinity transfer
      or steroid infusion. These differences in mRNA expression were accompanied by
      changes in the cellular distribution of the AQP1 protein between vascular
      endothelial and tubular epithelial cells.

PMID- 15850453
TI  - MIPDB: a relational database dedicated to MIP family proteins.
AB  - BACKGROUND INFORMATION: The MIPs (major intrinsic proteins) constitute a large
      family of membrane proteins that facilitate the passive transport of water and
      small neutral solutes across cell membranes. Since water is the most abundant
      molecule in all living organisms, the discovery of selective water-transporting
      channels called AQPs (aquaporins) has led to new knowledge on both the
      physiological and molecular mechanisms of membrane permeability. The MIPs are
      identified in Archaea, Bacteria and Eukaryota, and the rapid accumulation of new
      sequences in the database provides an opportunity for large-scale analysis, to
      identify functional and/or structural signatures or to infer evolutionary
      relationships. To help perform such an analysis, we have developed MIPDB
      (database for MIP proteins), a relational database dedicated to members of the
      MIP family. RESULTS: MIPDB is a motif-oriented database that integrates data on
      785 MIP proteins from more than 200 organisms and contains 230 distinct sequence
      motifs. MIPDB proposes the classification of MIP proteins into three functional
      subgroups: AQPs, glycerol-uptake facilitators and aquaglyceroporins. Plant MIPs
      are classified into three specific subgroups according to their subcellular
      distribution in the plasma membrane, tonoplast or the symbiosome membrane. Some
      motifs of the database are highly selective and can be used to predict the
      transport function or subcellular localization of unknown MIP proteins.
      CONCLUSIONS: MIPDB offers a user-friendly and intuitive interface for a rapid and
      easy access to MIP resources and to sequence analysis tools. MIPDB is a web
      application, publicly accessible at http://idefix.univ
      rennes1.fr:8080/Prot/index.html.

PMID- 15850454
TI  - Phylogeny and evolution of the major intrinsic protein family.
AB  - BACKGROUND INFORMATION: MIPs (major intrinsic proteins) form channels across
      biological membranes that control recruitment of water and small solutes such as
      glycerol and urea in all living organisms. Because of their widespread occurrence
      and large number, MIPs are a sound model system to understand evolutionary
      mechanisms underlying the generation of protein structural and functional
      diversity. With the recent increase in genomic projects, there is a considerable
      increase in the quantity and taxonomic range of MIPs in molecular databases.
      RESULTS: In the present study, I compiled more than 450 non-redundant amino acid
      sequences of MIPs from NCBI databases. Phylogenetic analyses using Bayesian
      inference reconstructed a statistically robust tree that allowed the
      classification of members of the family into two main evolutionary groups, the
      GLPs (glycerol-uptake facilitators or aquaglyceroporins) and the water transport
      channels or AQPs (aquaporins). Separate phylogenetic analyses of each of the MIP
      subfamilies were performed to determine the main groups of orthology. In
      addition, comparative sequence analyses were conducted to identify conserved
      signatures in the MIP molecule. CONCLUSIONS: The earliest and major gene
      duplication event in the history of the MIP family led to its main functional
      split into GLPs and AQPs. GLPs show typically one single copy in microbes
      (eubacteria, archaea and fungi), up to four paralogues in vertebrates and they
      are absent from plants. AQPs are usually single in microbes and show their
      greatest numbers and diversity in angiosperms and vertebrates. Functional
      recruitment of NOD26-like intrinsic proteins to glycerol transport due to the
      absence of GLPs in plants was highly supported. Acquisition of other MIP
      functions such as permeability to ammonia, arsenite or CO2 is restricted to
      particular MIP paralogues. Up to eight fairly conserved boxes were inferred in
      the primary sequence of the MIP molecule. All of them mapped on to one side of
      the channel except the conserved glycine residues from helices 2 and 5 that were
      found in the opposite side.

PMID- 15850455
TI  - Expression pattern of the Brachyury and Tbx2 homologues from the sponge Suberites
      domuncula.
AB  - BACKGROUND INFORMATION: T-box transcription factors are a large family of
      transcriptional regulators involved in many aspects of embryonic development. In
      a previous report, we described the isolation and genomic characterization of two
      T-box genes from the siliceous sponge Suberites domuncula: a Brachyury homologue,
      Sd-Bra, and a Tbx2 homologue, Sd-Tbx2. Elucidation of the genomic structure of Sd
      Bra allowed us to demonstrate the existence of two different isoforms, resulting
      from alternative splicing. Moreover, we demonstrated that the shorter isoform
      exists in two different glycosylation states. RESULTS: In the present study, we
      demonstrate a differential subcellular localization of the three Sd-Bra isoforms,
      suggesting that its differential nuclear import could be an important mechanism
      for its functional regulation. Furthermore, we demonstrate that Sd-Tbx2 exists
      only in one isoform, which is mainly localized in the nucleus. The pattern of
      expression of Sd-Bra and Sd-Tbx2 genes is analysed in sponge tissue, in gemmules
      and in cultured cells. CONCLUSION: These results suggest a conserved role for Sd
      Bra in the control of morphogenetic movements through the regulation of cell
      adhesion properties and the involvement of Sd-Tbx2 in the determination of cell
      identity in the early stages of differentiation, reminiscent of the function of
      Tbx2-3-4-5 in vertebrates during limb specification. Also, the fact that a
      Brachyury and a Tbx2 homologue exist in S. domuncula suggests that the first
      divergence from the ancestral Brachyury-like gene might be a Tbx2-like gene and
      not a Tbrain-like gene as had been previously suggested.

PMID- 15850456
TI  - Proton exclusion by an aquaglyceroprotein: a voltage clamp study.
AB  - BACKGROUND INFORMATION: In silico both orthodox aquaporins and aquaglyceroporins
      are shown to exclude protons. Supporting experimental evidence is available only
      for orthodox aquaporins. In contrast, the subset of the aquaporin water channel
      family that is permeable to glycerol and certain small, uncharged solutes has not
      yet been shown to exclude protons. Moreover, different aquaglyceroporins have
      been reported to conduct ions when reconstituted in planar bilayers. RESULTS: To
      clarify these discrepancies, we have measured proton permeability through the
      purified Escherichia coli glycerol facilitator (GlpF). Functional reconstitution
      into planar lipid bilayers was demonstrated by imposing an osmotic gradient
      across the membrane and detecting the resulting small changes in ionic
      concentration close to the membrane surface. The osmotic water flow corresponds
      to a GlpF single channel water permeability of 0.7x10(-14) cm(3).subunit(-1).s(
      1). Proton conductivity measurements carried out in the presence of a pH gradient
      (1 unit) revealed an upper limit of the H(+) (OH(-)) to H(2)O molecules transport
      stoichiometry of 2x10(-9). A significant GlpF-mediated ion conductivity was also
      not detectable. CONCLUSIONS: The lack of a physiologically relevant GlpF-mediated
      proton conductivity agrees well with predictions made by molecular dynamics
      simulations.

PMID- 15850457
TI  - Yeast Ypt11 is targeted to recycling endosomes in mammalian cells.
AB  - BACKGROUND INFORMATION: In yeast, Ypt11 or Ypt32 along with the highly homologous
      Ypt8 or Ypt31 has been reported to be an essential component of intra-Golgi
      trafficking and has been implicated in the budding of vesicles from the most
      distal Golgi compartment. RESULTS AND CONCLUSIONS: In the present study, we show
      that, in human cells, after heterologous expression of GFP-Ypt11 (where GFP
      stands for green fluorescent protein), the protein is targeted to transferrin
      positive recycling endosomes. This compartment has been shown to form extensive
      tubular networks on applying the drug Brefeldin A. We also show, by confocal
      fluorescent microscopy, that these networks also contain Rab11 in cells
      expressing CFP-Rab11a (where CFP stands for cyan fluorescent protein) fusion
      protein and that these structures are identical with those targeted by GFP-Ypt11.

PMID- 15850458
TI  - p38 mitogen-activated protein kinase (MAPK) first regulates filamentous actin at
      the 8-16-cell stage during preimplantation development.
AB  - BACKGROUND INFORMATION: The MAPK (mitogen-activated protein kinase) superfamily
      of proteins consists of four separate signalling cascades: the c-Jun N-terminal
      kinase or stress-activated protein kinases (JNK/SAPK); the ERKs (extracellular
      signal-regulated kinases); the ERK5 or big MAPK1; and the p38 MAPK group of
      protein kinases, all of which are highly conserved. To date, our studies have
      focused on defining the role of the p38 MAPK pathway during preimplantation
      development. p38 MAPK regulates actin filament formation through the downstream
      kinases MAPKAPK2/3 (MAPK-activated protein kinase 2/3) or MAPKAPK5 [PRAK (p38
      regulated/activated kinase)] and subsequently through HSP25/27 (heat-shock
      protein 25/27). We recently reported that 2-cell-stage murine embryos treated
      with cytokine-suppressive anti-inflammatory drugs (CSAIDtrade mark; SB203580 and
      SB220025) display a reversible blockade of development at the 8-16-cell stage,
      indicating that p38 (MAPK) activity is required to complete murine
      preimplantation development. In the present study, we have investigated the stage
      specific action and role of p38 MAPK in regulating filamentous actin during
      murine preimplantation development. RESULTS: Treatment of 8-cell-stage embryos
      with SB203580 and SB220025 (CSAIDtrade mark) resulted in a blockade of
      preimplantation development, loss of rhodamine phalloidin fluorescence, MK-p
      (phosphorylated MAPKAPK2/3), HSP-p (phosphorylated HSP25/27) and a redistribution
      of alpha-catenin immunofluorescence by 12 h of treatment. In contrast, treatment
      of 2- and 4-cell-stage embryos with CSAIDtrade mark drugs resulted in a loss of
      MK-p and HSP-p, but did not result in a loss of rhodamine phalloidin
      fluorescence. All these effects of p38 MAPK inhibition were reversed upon removal
      of the inhibitor, and development resumed in a delayed but normal manner to the
      blastocyst stage. Treatment of 8-cell embryos with PD098059 (ERK pathway
      inhibitor) did not affect development or fluorescence of MK-p, HSP-p or rhodamine
      phalloidin. CONCLUSION: Murine preimplantation development becomes dependent on
      p38 MAPK at the 8-16-cell stage, which corresponds to the stage when p38 MAPK
      first regulates filamentous actin during early development.

PMID- 15850459
TI  - Leishmania major encodes an unusual peroxidase that is a close homologue of plant
      ascorbate peroxidase: a novel role of the transmembrane domain.
AB  - Haem-containing enzymes (peroxidase and catalase) are widely distributed among
      prokaryotes and eukaryotes and play a vital role in H2O2 detoxification. But, to
      date, no haem-containing enzymatic defence against toxic H2O2 has been discovered
      in Leishmania species. We cloned, expressed and purified an unusual plant-like
      APX (ascorbate peroxidase) from Leishmania major (LmAPX) and characterized its
      catalytic parameters under steady-state conditions. Examination of its protein
      sequence indicated approx. 30-60% identity with other APXs. The N-terminal
      extension of LmAPX is characterized by a charged region followed by a stretch of
      22 amino acids containing a transmembrane domain. To understand how the
      transmembrane domain influences the structure-function of LmAPX, we generated,
      purified and extensively characterized a variant that lacked the transmembrane
      domain. Eliminating the transmembrane domain had no impact on substrate-binding
      affinity but slowed down ascorbate oxidation and increased resistance to H2O2
      dependent inactivation in the absence of electron donor by 480-fold. Spectral
      studies show that H2O2 can quickly oxidize the native enzyme to compound (II),
      which subsequently is reduced back to the native enzyme by an electron donor. In
      contrast, ascorbate-free transmembrane domain-containing enzyme did not react
      with H2O2, as revealed by the absence of compound (II) formation. Our findings
      suggest that the single copy LmAPX gene may play an important role in
      detoxification of H2O2 that is generated by endogenous processes and as a result
      of external influences such as the oxidative burst of infected host macrophages
      or during drug metabolism by Leishmania.

PMID- 15850460
TI  - Cecropin P1 and novel nematode cecropins: a bacteria-inducible antimicrobial
      peptide family in the nematode Ascaris suum.
AB  - Cecropin P1 was first identified as a mammalian antimicrobial peptide isolated
      from the pig intestine. Much research aimed at characterizing this peptide has
      been reported. Recently, the workers who discovered the peptide corrected their
      original conclusion, and confirmed that this peptide originates in fact from the
      pig intestinal parasitic nematode, Ascaris suum. In the present study, we carried
      out a semi-exhaustive search for bacteria-inducible transcripts in A. suum by the
      cDNA subtraction method. The transcripts encoding cecropin P1 and novel Ascaris
      cecropins, designated cecropins P2, P3 and P4, were found to be positively
      induced factors. Chemically synthesized Ascaris cecropins were bactericidal
      against a wide range of microbes, i.e. Gram-positive (Staphylococcus aureus,
      Bacillus subtilis and Micrococcus luteus) and Gram-negative (Pseudomonas
      aeruginosa, Salmonella typhimurium, Serratia marcescens and Esherichia coli)
      bacteria, and were weakly but detectably active against yeasts (Saccharomyces
      cerevisiae and Candida albicans). Cecropin P1-like sequences were also detected
      at least in two other species (Ascaris lumbricoides and Toxocara canis) of the
      Ascarididae. All Ascaris cecropin precursors contain an acidic pro-region
      connected by a tetra-basic cleavage site at the C-terminus. Such an acidic pro
      region is also reported to be present in the tunicate cecropin-type antimicrobial
      peptide styelin. On the basis of the evolutionary position of nematodes and
      tunicates, the ancestral cecropin may have contained the acidic pro-region at the
      C-terminus.

PMID- 15850461
TI  - The phosphorylation of CapZ-interacting protein (CapZIP) by stress-activated
      protein kinases triggers its dissociation from CapZ.
AB  - A protein expressed in immune cells and muscle was detected in muscle extracts as
      a substrate for several SAPKs (stress-activated protein kinases). It interacted
      specifically with the F-actin capping protein CapZ in splenocytes, and was
      therefore termed 'CapZIP' (CapZ-interacting protein). Human CapZIP was
      phosphorylated at Ser-179 and Ser-244 by MAPKAP-K2 (mitogen-activated protein
      kinase-activated protein kinase 2) or MAPKAP-K3 in vitro. Anisomycin induced the
      phosphorylation of CapZIP at Ser-179 in Jurkat cells, which was prevented by SB
      203580, consistent with phosphorylation by MAPKAP-K2 and/or MAPKAP-K3. However,
      osmotic shock-induced phosphorylation of Ser-179 was unaffected by SB 203580.
      These and other results suggest that CapZIP is phosphorylated at Ser-179 in cells
      by MAPKAP-K2/MAPKAP-K3, and at least one other protein kinase. Stress-activated
      MAP kinase family members phosphorylated human CapZIP at many sites, including
      Ser-68, Ser-83, Ser-108 and Ser-216. Ser-108 became phosphorylated when Jurkat
      cells were exposed to osmotic shock, which was unaffected by SB 203580 and/or PD
      184352, or in splenocytes from mice that do not express either SAPK3/p38gamma or
      SAPK4/p38delta. Our results suggest that CapZIP may be phosphorylated by JNK (c
      Jun N-terminal kinase), which phosphorylates CapZIP to >5 mol/mol within minutes
      in vitro. Osmotic shock or anisomycin triggered the dissociation of CapZIP from
      CapZ in Jurkat cells, suggesting that phosphorylation of CapZIP may regulate the
      ability of CapZ to remodel actin filament assembly in vivo.

PMID- 15850462
TI  - Treatment of hepatitis C.
AB  - The combination of pegylated interferon alpha and ribavirin has improved
      treatment success rates in patients with hepatitis C with sustained response
      rates of just over 50% overall and more than 70% for those with genotypes 2 and
      3. This article reviews the use of combination therapy, contraindications,
      factors influencing response and describes approaches to specific patient groups.

PMID- 15850463
TI  - Inhibition of hepatitis B virus replication in 2.2.15 cells by expressed shRNA.
AB  - Hepatitis B virus (HBV) infection is a worldwide health problem. To determine
      whether RNA interference (RNAi) could inhibit ongoing HBV replication in 2.2.15
      cells, we constructed shRNA-producing vector pU6P based on the mouse U6 RNA
      promoter and cloned 12 targeted sequences against HBV into the vector, resulting
      in a series of pU6-siHBV vectors. The recombinant vectors were transfected into
      2.2.15 cells, HBsAg and HBeAg in cultured media were assayed using enzyme-linked
      immunosorbent assay at various days after transfection. The amount of HBV DNA in
      the culture medium was quantitated by real-time polymerase chain reaction. HBsAg
      and HBeAg expression were inhibited by 72.8 +/- 5.4% (P = 0.00003) and 55.8 +/-
      6.2% (P = 0.000026), respectively, 4 days after transfection with pU6-siHBV5. The
      greatest inhibition of HBV DNA was decreased by approximately 1.9-fold (P =
      0.013) on day 6 post transfection with pU6-siHBV11 compared with that of empty
      vector. No change was found for HBV protein expression and DNA replication on pU6
      siGFP (negative control) transfected cells. Our data demonstrate that the
      transfection of HBV-targeted shRNA-producing vector in 2.2.15 cells could inhibit
      the HBV protein expression and HBV DNA replication specifically. RNAi may be
      considered as a potential antiviral approach for human HBV infection.

PMID- 15850464
TI  - Mutations in the E2-PePHD region of hepatitis C virus type 1b in patients with
      hepatocellular carcinoma.
AB  - An interaction between the protein kinase (PKR)-eIF2-alpha phosphorylation
      homology domain (PePHD) within the E2 protein of hepatitis C virus (HCV) and cell
      protein kinase (PKR) may affect the control of protein synthesis and cell growth.
      In an attempt to investigate the genetic variability of the E2-PePHD domain in
      hepatocellular carcinoma (HCC), we studied sera and liver tissues from HCC
      patients. The partial E2-PePHD region was analysed by direct sequencing of the
      sera of 47 HCCs in cirrhotic livers and 31 cases of chronic active hepatitis
      (CAH), and tumoral and non-tumoral liver tissues from 13 HCC patients. A similar
      number of mutations was detected within the E2 domain in the HCC and CAH cases,
      but nine of the 47 HCCs (19%) showed an amino acid (aa) mutation at position 660,
      eight of which involved a change in the same aa (alanine instead of serine; A/S).
      No such mutation was detected in any of the PePHD sequences from the CAH
      patients: this difference was statistically significant (P = 0.008). The aa
      change at position 660 was also found in two sequences from tumoral but not non
      tumoral tissue from the same liver. The analysis of 461 sequences obtained from
      GenBank supports the conclusion that the observed aa change is an infrequent
      event in HCV-infected patients, thus suggesting that it could be associated with
      HCC.

PMID- 15850465
TI  - Characteristic sequence changes of hepatitis C virus genotype 2b associated with
      sustained biochemical response to IFN therapy.
AB  - In hepatitis C virus (HCV) genotype 2b infection, viral eradication (sustained
      viral response; sVR) is obtained in about 40% by interferon monotherapy, whereas
      a considerable proportion of non-sVR patients exhibit sustained biochemical
      response (sBR) showing normal biochemical values despite persistent viraemia.
      However, the mechanism of sBR has not yet been established. In this study, we
      analysed serial changes in full-length sequences of HCV genotype 2b before and
      after interferon (IFN) therapy in five patients with sBR and five with no
      response (NR; persistent viraemia and abnormal biochemical values after IFN
      therapy). The overall substitution rate of amino acids in the full-length HCV
      genome was higher in the sBR group than in the NR group [2.22 +/- 0.48 (10(-3)
      changes/site/year) vs 1.04 +/- 0.30: P = 0.002]. When the genetic changes were
      analysed for individual HCV proteins, the sBR group had significantly higher
      substitution rates of amino acid in NS4A [8.82 +/- 2.80 (10(-3)
      changes/site/year) vs 0: P = 0.001]. These amino acid changes in sBR were mainly
      located in the binding motifs of HLA class I molecules including those frequently
      found in the Japanese population. These results demonstrated that the greater
      amino acid changes of HCV arising during interferon therapy are associated with
      the establishment of sBR. Although functional significance of these changes
      awaits further investigation, the finding that amino acid changes in NS4A in sBR
      patients are mainly located in the HLA class I binding motifs illustrated the
      potential roles of the escape mutations of HCV genome from CTLs in the decreasing
      activities of hepatitis in sBR.

PMID- 15850466
TI  - Lamivudine vs lamivudine and interferon combination treatment of HBeAg(-) chronic
      hepatitis B.
AB  - To determine whether combination treatment of HBeAg(-) chronic hepatitis B is
      beneficial we studied 78 patients with HBeAg(-), HBV DNA-positive chronic
      hepatitis B who were randomized to lamivudine, 100 mg, qd, for 12 months or
      lamivudine-interferon (9 MU, t.i.w.) in combination. In the combination arm, 2
      months of lamivudine treatment preceded 10 months of combination treatment.
      Biochemical, virologic and histologic responses were assessed at the end of
      treatment, after six and a median 27 months of drug-free follow-up (short- and
      long-term follow-up, respectively). Virologic response was defined as
      undetectable HBV DNA with a hybridization assay and biochemical response as
      normal alanine aminotransferase (ALT). Change in HBV DNA was also assessed by
      real-time polymerase chain reaction (PCR). Presence of YMDD mutants at the end of
      treatment was investigated with a line probe assay. Both treatment regimes led to
      a median 2 log decline in HBV DNA levels. Virologic end of treatment responses
      were 90 and 92% with mono- and combination treatment, respectively. Corresponding
      virologic responses at short- and long-term follow-up were 59 and 54%, and 27 and
      25%, respectively. Patients having a baseline HBV DNA value > or =200 pg/mL were
      more likely to relapse within 6 months off therapy than those patients with a
      baseline HBV DNA level <200 pg/mL (P = 0.041). YMDD mutants were observed in 53%
      of patients receiving lamivudine compared with 24% of patients receiving the
      combination regime (P = 0.017). In conclusion, efficacy of combination treatment
      is similar to lamivudine monotherapy. However, combination treatment decreases
      the development of YMDD mutant strains compared with lamivudine monotherapy.

PMID- 15850467
TI  - Gamma-glutamyltransferase in fine-needle liver biopsies of subjects with chronic
      hepatitis C.
AB  - Serum gamma-glutamyltransferase (GGT) is considered as a sensitive but rather
      nonspecific marker of hepatobiliary disease, including chronic hepatitis C virus
      (HCV) infection. Although its increase in HCV infection is associated with poor
      response to interferon-alpha (IFN-alpha) and poor prognosis, there is little
      knowledge of the reasons of its increase during disease. Immunohistochemistry and
      enzyme histochemistry were performed on fine-needle biopsies of subjects with HCV
      infection. GGT was detected in the lumen of bile ducts and in bile canaliculi.
      Furthermore, in subjects with elevated serum GGT, immunoreactive and
      catalytically active GGT was also detected on the sinusoidal surface of
      hepatocytes and diffuse cytoplasmic positivity appeared in isolated hepatocytes
      and hepatocellular foci. Antigen unmasking procedures showed the presence of GGT
      in the cytoplasm of mature and immature bile cells and of inflammatory cells.
      These results suggest that during chronic HCV infection there is a general
      enhancement of GGT activity within the liver. As the activity of several
      inflammatory mediators, such as leukotrienes, nitric oxide, and interleukins is
      modulated by GGT activity, the present findings suggest a direct relationship
      between serum GGT, enhanced intrahepatic GGT activity and prognosis and
      therapeutic outcome of chronic HCV infection.

PMID- 15850468
TI  - Immunomodulatory effects of selective leucocytapheresis as a new adjunct to
      interferon-alpha2b plus ribavirin combination therapy: a prospective study in
      patients with high plasma HCV viraemia.
AB  - Efficacy of interferon-alpha2b (IFN) + ribavirin (IFN/RBV) combination in
      patients with high plasma hepatitis C virus (HCV) is very poor. Dysregulated CD4+
      /CD8+ T cells is involved in both impaired cell-mediated immunity and resistance
      to IFN. Adsorptive granulocytes and monocytes apheresis (GMA) can remove infected
      leucocytes which are extrahepatic HCV reservoirs and also has been associated
      with intriguing immunomodulation and increases in CD4+ T cells. Our aim was to
      see if GMA enhances the efficacy of IFN/RBV. Twenty-four patients, 13 IFN
      resistant and 11 IFN naive were enrolled. Seventeen were genotype 1b and 7 were
      2a or 2b. Mean plasma HCV-RNA was 612.9 (100-850) kIU/mL and alanine
      aminotransferase, 108 (41-373) U/L. GMA was performed with Adacolumn at one
      session/day for five consecutive days and IFN/RBV was started within 24 h after
      the last GMA session. Daily 6 million units of IFN, six times/week for 2 weeks
      and then three times/week for 22 weeks were given with RBV (600-800
      mg/day/patient). Patients were followed for 6 months. GMA was associated with a
      significant increase in lymphocyte counts, complement activation fragment C3a and
      falls in tissue necrosis factor-alpha, and IL-8 produced by peripheral blood
      leucocytes. At week 24, 20 of 24 patients (83%) were HCV negative and by end of
      follow-up (week 49), the remission was sustained in 14 of 24 patients (58%)
      including 100% of patients with 2a or 2b. In conclusion, enhanced efficacy of
      IFN/RBV following GMA might be attributed to a more efficient immune function and
      a renewed IFN signaling towards HCV.

PMID- 15850469
TI  - Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and
      interferon alpha-2b plus ribavirin in treating Chinese patients with chronic
      hepatitis C in Taiwan.
AB  - Previous studies in Caucasian patients showed treatment of chronic hepatitis C
      with pegylated interferon/ribavirin was well tolerated, and produced a higher
      response rate especially in genotype 1 infections. However, it is unknown whether
      this conclusion can be extrapolated to patients with Chinese ethnic origin. A
      total of 153 patients with biopsy-proven chronic hepatitis C were randomly
      assigned to receive either weekly injection of peginterferon alpha-2b 1.5 mcg/kg
      plus oral ribavirin (1000 or 1200 mg/day, depending on body weight) (PEG group, n
      = 76) or 3 MU of interferon alpha-2b t.i.w. plus ribavirin (IFN group, n = 77)
      for 24 weeks. Sustained virological response (SVR) was defined as the sustained
      disappearance of serum hepatitis C virus (HCV) RNA at 24 weeks after the end of
      treatment by polymerase chain reaction assay. Baseline demographic, viral and
      histological characteristics were comparable between the two groups. Using an
      intent-to-treat analysis, HCV genotype 1 patients showed a significantly higher
      SVR in patients receiving PEG-IFN rather than IFN (65.8%vs 41.0%, P = 0.019), but
      no difference was found in genotype non-1 patients (PEG vs IFN: 68.4%vs 86.8%, P
      = 0.060). Genotype 1 patients (28.6%) in the PEG-IFN group relapsed, as compared
      with 52.9% in the IFN group (P = 0.040). Multivariate analyses showed early
      virological response at week 12 of therapy and genotype non-1 were significant
      predictors to SVR. As compared with the IFN group, patients receiving PEG-IFN had
      a significantly higher rate of discontinuation, dose reduction, fever, headache,
      insomnia, leucopenia and thrombocytopenia. In genotype 1 chronic hepatitis C
      Chinese patient, PEG-IFNalpha2b ribavirin had significantly better SVR and lower
      relapse rate when compared to IFN/ribavirin. Both regimens can be recommended for
      genotype non-1 chronic hepatitis C Chinese patients. However, a higher rate of
      adverse events and discontinuance of therapy were noted in patients treated with
      PEG-IFNalpha2b ribavirin.

PMID- 15850470
TI  - A randomized controlled trial of pegylated interferon alpha-2a (40 KD) or
      interferon alpha-2a plus ribavirin and amantadine vs interferon alpha-2a and
      ribavirin in treatment-naive patients with chronic hepatitis C.
AB  - We determined whether triple therapy comprising amantadine (AMA), ribavirin (RBV)
      and either peginterferon (PEG-IFN) alpha-2a or conventional IFN alpha-2a would
      improve sustained virological response (SVR) rates over dual therapy with IFN
      alpha-2a and RBV in patients with chronic HCV infection. A total of 362 treatment
      naive patients were randomized to 48 weeks of treatment with: PEG-IFN alpha-2a
      180 microg/week (group A) or IFN alpha-2a 3 MU tiw (groups B and C). All patients
      received RBV 1000 or 1200 mg/day and those in groups A and B received AMA 200
      mg/day. SVR was defined as an undetectable HCV RNA after 24 weeks of untreated
      follow-up. At the end of therapy, 74.4% (95% CI 0.66-0.82) of patients in group A
      were HCV RNA-negative compared with 42.5% (95% CI 0.33-0.50) of those in group B
      (P = 0.0001) and 48.8% (95% CI 0.40-0.56) of those in group C. SVR was achieved
      in a significantly greater proportion of patients in group A compared with groups
      B and C: 65.3% (95% CI 0.53-0.56), 33.3% (95% CI 0.25-0.41) and 44.6% (95% CI
      0.36-0.53; P = 0.0001) respectively. In patients with genotype 1, SVR rates were
      55.2, 22.8 and 28.8% with the three regimens respectively. Factors independently
      associated with SVR were HCV genotype 2 or 3, therapy with PEG-IFN, female gender
      and age. In treatment-naive patients with chronic hepatitis C, triple therapy
      with PEG-IFN alpha-2a, RBV and AMA produces higher SVR than dual or triple
      therapy with conventional IFN alpha-2a.

PMID- 15850472
TI  - Apoptotic cytokeratin 18 neoepitopes in serum of patients with chronic hepatitis
      C.
AB  - In patients with chronic hepatitis C, alanine aminotransferase (ALT) levels do
      not accurately reflect the extent of liver inflammation. The discrepancy between
      ALT level and liver damage could be related to the mode of cell death. In the
      present study, we quantified serum levels of apoptotic cytokeratin 18 (CK-18)
      neoepitopes that are generated by activated caspases during apoptosis. Apoptotic
      CK-18 neoepitopes were quantified by enzyme linked immunosorbent assay in sera
      from patients with chronic hepatitis C and elevated ALT levels (n = 72), patients
      with chronic hepatitis C and persistently normal ALT levels (n = 27) and healthy
      controls (n = 19). Serum CK-18 neoepitope levels were strongly correlated with
      ALT (r = 0.659, P < 0.0001) and the histology activity index (r = 0.374, P <
      0.001). Patients with chronic hepatitis C and persistently normal ALT levels had
      higher apoptotic CK-18 neoepitope levels than healthy controls (P = 0.03) but
      lower levels than patients with chronic hepatitis C and elevated ALT levels (P <
      0.001). Highest serum CK-18 neoepitope levels were observed in patients with
      cirrhosis (P = 0.002). Hence apoptotic CK-18 neoepitopes in serum of patients
      with chronic hepatitis C are associated with ALT level and histological liver
      damage. Serum apoptotic CK-18 neoepitope levels are elevated both in patients
      with chronic hepatitis C and elevated ALT levels as well as in patients with
      normal ALT levels indicating that also patients with chronic hepatitis C and
      normal ALT have an increased hepatocyte loss by apoptosis.

PMID- 15850471
TI  - The efficacy and safety of thymosin alpha-1 in Japanese patients with chronic
      hepatitis B; results from a randomized clinical trial.
AB  - Thymalfasin (thymosin alpha-1; Talpha1) is a 28-amino acid polypeptide that has
      shown efficacy in the treatment of chronic hepatitis B virus (HBV) infection. The
      objective of this study was to evaluate the long-term, dose-related efficacy and
      safety of Talpha1 treatment in chronic hepatitis B patients with positive HBV-DNA
      and abnormally high alanine aminotransferase (ALT) levels. A total of 316
      patients were randomized to receive either 0.8 or 1.6 mg of Talpha1 monotherapy
      for 24 weeks. At the end of the 72-week observation period (12 months after
      cessation of therapy), 36.4% of patients in the 1.6-mg treatment group achieved
      normalization of ALT, 30% achieved clearance of HBV-DNA by branched DNA vs 15% by
      transcription-mediated amplification, and 22.8% achieved clearance of HBe
      antigen. Patients in the 0.8-mg treatment group achieved similar efficacy rates,
      although patients with advanced fibrosis demonstrated a significantly better
      response rate when treated with 1.6 mg of Talpha1 monotherapy vs 0.8 mg (as
      determined by intragroup analysis; patients were not stratified by liver biopsy).
      All adverse drug reactions were mild and most involved the fluctuation of liver
      enzymes, which was most likely related to the positive immune effects caused by
      the response to Talpha1 treatment. Adverse event incidence was similar in the 1.6
      and 0.8-mg treatment groups. In conclusion, Talpha1 at doses of 0.8 and 1.6 mg
      exhibits long-term efficacy against hepatitis B with a good safety profile.

PMID- 15850473
TI  - Determinants of acquiring hepatitis A virus disease in a large Italian region in
      endemic and epidemic periods.
AB  - Viral hepatitis A is endemic in Puglia region (southeast Italy). Over the last 13
      years, annual incidence rates have ranged from 4 to 138 per 100,000 inhabitants
      and periodical regional epidemics have been described. Between 1 January 1996 and
      31 December 1997 over 11,000 cases of hepatitis A were reported accounting for an
      annual incidence rate over 130/100,000. To identify exposures during the
      epidemics, a case-control study was performed in two different rounds and since
      1997, an enhanced surveillance system has permitted the monitoring of exposures
      of subsequent cases. Raw seafood consumption was identified as the major risk
      factor for hepatitis A. Adjusted odds ratio and 95% confidence intervals for this
      exposure from the first round of the case-control study was 38.6 (12.2-122.4) and
      for the second round for consumption of raw mussels it was 30.7 (16.0-52.0).
      Hepatitis A epidemiology in Puglia is consistent with an endemic situation
      sustained by locally contaminated seafood consumed raw and by the recurrence of
      large epidemics, where size is influenced by the accumulation of susceptible
      subjects in the population.

PMID- 15850474
TI  - Detection of multiple hepatitis C virus genotypes in a cohort of injecting drug
      users.
AB  - Multiple genotypes of the hepatitis C virus (HCV) were detected in five of 138
      HCV RNA positive injecting drug users (IDUs) recruited in Melbourne, Australia.
      Two were detected by combined LiPA and core and NS5a region sequencing, and three
      more (selected for testing due to their high-risk behaviour) by heteroduplex
      mobility analysis. We conclude that the true prevalence of mixed infection in
      IDUs is undoubtedly higher than the 3.6% (five of 138) we observed, and is
      underestimated by LiPA, the most common method of genotyping. As responsiveness
      to HCV treatment varies significantly with genotype, a high prevalence of mixed
      HCV infections in IDUs must diminish overall treatment efficacy and lessen our
      ability to reduce the burden of HCV-related disease.

PMID- 15850475
TI  - HBsAg-negative hepatitis B virus infections in hepatitis C virus-associated
      hepatocellular carcinoma.
AB  - This study was conducted to evaluate reports that hepatitis B virus (HBV) DNA
      sequences can be found in the serum and/or tumour tissue from some hepatocellular
      carcinoma (HCC) patients who have no detectable hepatitis B surface antigen
      (HBsAg) in their sera. Such HBV infections would be highly atypical, because
      prospective studies have shown a clear succession of specific serologic markers
      during and after most HBV infections. As most HBsAg-negative HCC patients in
      Japan have hepatitis C virus (HCV) infections, the present study was conducted to
      determine whether some of these patients actually have unrecognized HBV
      infections. Thirty newly diagnosed HCC patients from Kurume, Japan, with antibody
      to the hepatitis C virus (anti-HCV) were studied. None of the 30 had HBsAg
      detectable in their serum. Of 22 for whom test results for antibodies to the
      hepatitis B core antigen (anti-HBc) and antibodies to HBsAg (anti-HBs) were
      available, 14 (64%) had anti-HBc and anti-HBs, four (18%) had anti-HBc alone, and
      four (18%) had no HBV markers. Nested polymerase chain reaction was used to
      detect the HBV surface (S), core (C), polymerase (P) and core promoter gene
      sequences in the HCC tissues and in the adjacent nontumorous liver tissues. HBV
      DNA was detected in HCC and/or adjacent nontumorous liver in 22 of 30 (73%)
      patients [detected in both HCC and nontumorous liver in 19/30 patients (63%)].
      Among the 22 patients with detectable HBV DNA, more than one HBV gene was
      detected in 10 (46%). Among the four patients whose sera were negative for all
      HBV markers, three had HBV DNA in either HCC and nontumorous liver (two cases) or
      only in the nontumorous liver (one case); HBV DNA could not be detected in
      tissues from the fourth patient. In 18 of 21 (86%) patients with detectable HBV
      core promoter sequences, mutations at both nucleotides 1762 (A-GT) and 1764 (G-A)
      in the core promoter region were found. No deletions were detected in the core
      promoter gene region of the type reported to be associated with some cases of
      HBsAg-negative HBV infection. Thus, HBV DNA was detectable in 22 (73%) HBsAg
      negative, anti-HCV-positive HCCs, including three (10%) who were also negative
      for anti-HBc and anti-HBs. HBV mutations at both nucleotides 1762 (A-GT) and 1764
      (G-A) in the core promoter region were found in the majority of cases, mutations
      that have previously been reported in HBV that is integrated in HCC DNA. In
      serologic surveys to determine etiologic associations of HCC, patients such as
      those in this study would have been incorrectly designated as having 'HCV
      associated HCC,' whereas the data in this study suggest that HBV could have
      played a role in the development of their HCCs.

PMID- 15850476
TI  - Prevalence and sexual risk of hepatitis C virus infection when human
      immunodeficiency virus was acquired through sexual intercourse among patients of
      the Lyon University Hospitals, France, 1992-2002.
AB  - To report the prevalence and the risk factors for hepatitis C virus (HCV)
      infection in a hospital cohort of 2691 sexually human immunodeficiency virus
      (HIV)-infected patients. The patients were enrolled in the Lyon section of the
      French Hospital Database on HIV between 1992 and 2002. Baseline characteristics
      were analysed. The detection of HCV-antibodies (Ab) was used for diagnosis. The
      HCV-Ab prevalence rate was 5.7 and 12.89% for individuals infected by HIV after
      homosexual intercourse or heterosexual intercourse, respectively. HCV-Ab was
      three times more frequently found among patients infected with HIV after
      heterosexual intercourse compared with patients infected with HIV after
      homosexual intercourse (adjusted OR: 3.2, 95% CI: 2.28-4.62, multiple logistic
      regression). The risk of HCV infection among HIV-infected individuals differed
      according to sexual behaviour. The determinants associated with HCV transmission
      through the sexual route needs to be explored further.

PMID- 15850477
TI  - Detailed protein sequence alignment based on Spectral Similarity Score (SSS).
AB  - BACKGROUND: The chemical property and biological function of a protein is a
      direct consequence of its primary structure. Several algorithms have been
      developed which determine alignment and similarity of primary protein sequences.
      However, character based similarity cannot provide insight into the structural
      aspects of a protein. We present a method based on spectral similarity to compare
      subsequences of amino acids that behave similarly but are not aligned well by
      considering amino acids as mere characters. This approach finds a similarity
      score between sequences based on any given attribute, like hydrophobicity of
      amino acids, on the basis of spectral information after partial conversion to the
      frequency domain. RESULTS: Distance matrices of various branches of the human
      kinome, that is the full complement of human kinases, were developed that matched
      the phylogenetic tree of the human kinome establishing the efficacy of the global
      alignment of the algorithm. PKCd and PKCe kinases share close biological
      properties and structural similarities but do not give high scores with character
      based alignments. Detailed comparison established close similarities between
      subsequences that do not have any significant character identity. We compared
      their known 3D structures to establish that the algorithm is able to pick
      subsequences that are not considered similar by character based matching
      algorithms but share structural similarities. Similarly many subsequences with
      low character identity were picked between xyna-theau and xyna-clotm F/10
      xylanases. Comparison of 3D structures of the subsequences confirmed the claim of
      similarity in structure. CONCLUSION: An algorithm is developed which is inspired
      by successful application of spectral similarity applied to music sequences. The
      method captures subsequences that do not align by traditional character based
      alignment tools but give rise to similar secondary and tertiary structures. The
      Spectral Similarity Score (SSS) is an extension to the conventional similarity
      methods and results indicate that it holds a strong potential for analysis of
      various biological sequences and structural variations in proteins.

PMID- 15850478
TI  - Detection of target DNA using fluorescent cationic polymer and peptide nucleic
      acid probes on solid support.
AB  - BACKGROUND: Nucleic acids detection using microarrays requires labelling of
      target nucleic acids with fluorophores or other reporter molecules prior to
      hybridization. RESULTS: Using surface-bound peptide nucleic acids (PNA) probes
      and soluble fluorescent cationic polythiophenes, we show a simple and sensitive
      electrostatic approach to detect and identify unlabelled target nucleic acid on
      microarray. CONCLUSION: This simple methodology opens exciting possibilities for
      applied genetic analysis for the diagnosis of infections, identification of
      genetic mutations, and forensic inquiries. This electrostatic strategy could also
      be used with other nucleic acid detection methods such as electrochemistry,
      silver staining, metallization, quantum dots, or electrochemical dyes.

PMID- 15850479
TI  - Quadratic regression analysis for gene discovery and pattern recognition for non
      cyclic short time-course microarray experiments.
AB  - BACKGROUND: Cluster analyses are used to analyze microarray time-course data for
      gene discovery and pattern recognition. However, in general, these methods do not
      take advantage of the fact that time is a continuous variable, and existing
      clustering methods often group biologically unrelated genes together. RESULTS: We
      propose a quadratic regression method for identification of differentially
      expressed genes and classification of genes based on their temporal expression
      profiles for non-cyclic short time-course microarray data. This method treats
      time as a continuous variable, therefore preserves actual time information. We
      applied this method to a microarray time-course study of gene expression at short
      time intervals following deafferentation of olfactory receptor neurons. Nine
      regression patterns have been identified and shown to fit gene expression
      profiles better than k-means clusters. EASE analysis identified over-represented
      functional groups in each regression pattern and each k-means cluster, which
      further demonstrated that the regression method provided more biologically
      meaningful classifications of gene expression profiles than the k-means
      clustering method. Comparison with Peddada et al.'s order-restricted inference
      method showed that our method provides a different perspective on the temporal
      gene profiles. Reliability study indicates that regression patterns have the
      highest reliabilities. CONCLUSION: Our results demonstrate that the proposed
      quadratic regression method improves gene discovery and pattern recognition for
      non-cyclic short time-course microarray data. With a freely accessible Excel
      macro, investigators can readily apply this method to their microarray data.

PMID- 15850480
TI  - Good governance and good health: The role of societal structures in the human
      immunodeficiency virus pandemic.
AB  - BACKGROUND: Only governments sensitive to the demands of their citizens
      appropriately respond to needs of their nation. Based on Professor Amartya Sen's
      analysis of the link between famine and democracy, the following null hypothesis
      was tested: "Human Immunodeficiency Virus (HIV) prevalence is not associated with
      governance". METHODS: Governance has been divided by a recent World Bank paper
      into six dimensions. These include Voice and Accountability, Political Stability
      and Absence of Violence, Government Effectiveness, Regulatory Quality, Rule of
      Law and the Control of Corruption. The 2002 adult HIV prevalence estimates were
      obtained from UNAIDS. Additional health and economic variables were collected
      from multiple sources to illustrate the development needs of countries. RESULTS:
      The null hypothesis was rejected for each dimension of governance for all 149
      countries with UNAIDS HIV prevalence estimates. When these nations were divided
      into three groups, the median (range) HIV prevalence estimates remained constant
      at 0.7% (0.05 - 33.7%) and 0.75% (0.05% - 33.4%) for the lower and middle mean
      governance groups respectively despite improvements in other health and economic
      indices. The median HIV prevalence estimates in the higher mean governance group
      was 0.2% (0.05 - 38.8%). CONCLUSION: HIV prevalence is significantly associated
      with poor governance. International public health programs need to address
      societal structures in order to create strong foundations upon which effective
      healthcare interventions can be implemented.

PMID- 15850482
TI  - Being uninformed on informed consent: a pilot survey of medical education
      faculty.
AB  - BACKGROUND: This paper describes a pilot survey of faculty involved in medical
      education. The questionnaire focuses on their understanding of IRB policies at
      their institution, specifically in relation to the use of student assessment and
      curriculum evaluation information for scholarship. METHODS: An anonymous survey
      was distributed to medical educators in a variety of venues. Two brief scenarios
      of typical student assessment or curriculum evaluation activities were presented
      and respondents were asked to indicate their likely course of action related to
      IRB approval. The questionnaire also asked respondents about their knowledge of
      institutional policies related to IRB approval. RESULTS: A total of 121 completed
      surveys were obtained; 59 (50%) respondents identified themselves as from
      community-based medical schools. For the first scenario, 78 respondents (66%)
      would have contact with the IRB; this increased to 97 respondents (82%) for the
      second scenario. For both scenarios, contact with the IRB was less likely among
      respondents from research-intensive institutions. Sixty respondents (55%) were
      unsure if their institutions had policies addressing evaluation data used for
      scholarship. Fifty respondents (41%) indicated no prior discussions at their
      institutions regarding IRB requirements. CONCLUSION: Many faculty members are
      unaware of IRB policies at their medical schools related to the use of medical
      student information. To the extent that policies are in place, they are highly
      variable across schools suggesting little standardization in faculty
      understanding and/or institutional implementation. Principles to guide faculty
      decision-making are provided.

PMID- 15850481
TI  - The Microbial Rosetta Stone Database: a compilation of global and emerging
      infectious microorganisms and bioterrorist threat agents.
AB  - BACKGROUND: Thousands of different microorganisms affect the health, safety, and
      economic stability of populations. Many different medical and governmental
      organizations have created lists of the pathogenic microorganisms relevant to
      their missions; however, the nomenclature for biological agents on these lists
      and pathogens described in the literature is inexact. This ambiguity can be a
      significant block to effective communication among the diverse communities that
      must deal with epidemics or bioterrorist attacks. RESULTS: We have developed a
      database known as the Microbial Rosetta Stone. The database relates microorganism
      names, taxonomic classifications, diseases, specific detection and treatment
      protocols, and relevant literature. The database structure facilitates linkage to
      public genomic databases. This paper focuses on the information in the database
      for pathogens that impact global public health, emerging infectious organisms,
      and bioterrorist threat agents. CONCLUSION: The Microbial Rosetta Stone is
      available at http://www.microbialrosettastone.com/. The database provides public
      access to up-to-date taxonomic classifications of organisms that cause human
      diseases, improves the consistency of nomenclature in disease reporting, and
      provides useful links between different public genomic and public health
      databases.

PMID- 15850483
TI  - Morphological and growth altering effects of Cisplatin in C. albicans using
      fluorescence microscopy.
AB  - Changes in morphology and growth curve of Candida albicans in response to
      treatment by Cisplatin has been studied using fluorescence staining with ethidium
      bromide. Treatment with Cisplatin was found to markedly inhibit hyphae and ovoid
      growth as revealed by ethidium bromide staining of drug treated cells. These
      changes were concomitant with inhibitory effects on the growth curve with respect
      to untreated cells. Presence of Cisplatin not only caused suppression in the
      limiting values in the growth curve, but also caused a slight left shift in the
      EC50 values. Some of the ovoid cells undergoing poisoning with cisplatin were
      found to be unusually enlarged before undergoing their natural fate thus
      suggesting formation of similar cytotoxic end products with DNA.

PMID- 15850484
TI  - Identification of children who may benefit from self-hypnosis at a pediatric
      pulmonary center.
AB  - BACKGROUND: Emotional difficulties can trigger respiratory symptoms. Thus,
      children presenting with respiratory complaints may benefit from a psychological
      intervention. The purpose of this study was to define the proportion of patients
      referred to a Pediatric Pulmonary Center who may benefit from instruction in self
      hypnosis, as a psychological intervention. METHODS: A retrospective chart review
      was conducted for all newly referred patients to the SUNY Upstate Medical
      University Pediatric Pulmonary Center during an 18 month period beginning January
      1, 2000. Patients were offered hypnosis if they presented with symptoms or signs
      suggestive of psychological difficulties. Hypnosis was taught in one or two 15-45
      minute sessions by a pediatric pulmonologist. RESULTS: Of 725 new referrals, 424
      were 0-5 years old, 193 were 6-11 years old, and 108 were 12-18 years old.
      Diagnoses of anxiety, habit cough, or vocal cord dysfunction accounted for 1% of
      the 0-5 year olds, 20% of the 6-11 year olds, and 31% of the 12-18 year olds.
      Hypnotherapy was offered to 1% of 0-5 year olds, 36% of 6-11 year olds, and 55%
      of 12-18 year olds. Of 81 patients who received instruction in self-hypnosis for
      anxiety, cough, chest pain, dyspnea, or inspiratory difficulties, 75% returned
      for follow-up, and among the returning patients 95% reported improvement or
      resolution of their symptoms. CONCLUSION: A large number of patients referred to
      a Pediatric Pulmonary Center appeared to benefit from instruction in self
      hypnosis, which can be taught easily as a psychological intervention.

PMID- 15850485
TI  - The strengths and limitations of meta-analyses based on aggregate data.
AB  - BACKGROUND: Properly performed systematic reviews and meta-analyses are thought
      by many to represent among the highest level of evidence addressing important
      clinical issues. Few would disagree that meta-analyses based on individual
      patient data (IPD) offer several advantages and represent the standard to which
      all other systematic reviews should be compared. METHODS: All cancer-related meta
      analyses cited in Medline were classified as based on aggregate or individual
      patient data. A review was then undertaken of all reports comparing the
      comparative strengths and limitations of meta-analyses using either aggregate or
      individual patient data. RESULTS: The majority of published meta-analyses are
      based on summary or aggregate patient data (APD). Reasons suggested for this
      include the considerable resources, years of study and often, broad international
      cooperation required for IPD meta-analyses. Many of the most important features
      of systematic reviews including formal meta-analyses are addressed by both IPD
      and APD meta-analyses. The need for defining an explicit and relevant clinical
      question, exhaustively searching for the totality of evidence, meticulous and
      unbiased data transfer or extraction, assessment of between study heterogeneity
      and the use of appropriate statistical methods for estimating summary effect
      measures are essentially the same for the two approaches. CONCLUSION: IPD offers
      advantages and, when feasible, should be considered the best opportunity to
      summarize the results of multiple studies. However, the resources, time and
      cooperation required for such studies will continue to limit their use in many
      important areas of clinical medicine which can be meaningfully and cost
      effectively approached by properly performed APD meta-analyses. APD meta-analyses
      continue to be the mainstay of systematic reviews utilized by the US Preventive
      Services Task Force, the Cochrane Collaboration and many professional societies
      to support clinical practice guidelines.

PMID- 15850486
TI  - Validation of a brief telephone battery for neurocognitive assessment of patients
      with pulmonary arterial hypertension.
AB  - BACKGROUND: The effects of pulmonary arterial hypertension on brain function are
      not understood, despite patients' frequent complaints of cognitive difficulties.
      Using clinical instruments normally administered during standard in-person
      assessment of neurocognitive function in adults, we assembled a battery of tests
      designed for administration over the telephone. The purpose was to improve
      patient participation, facilitate repeated test administration, and reduce the
      cost of research on the neuropsychological consequences of acute and chronic
      cardiorespiratory diseases. We undertook this study to validate telephone
      administration of the tests. METHODS: 23 adults with pulmonary arterial
      hypertension underwent neurocognitive assessment using both standard in-person
      and telephone test administration, and the results of the two methods compared
      using interclass correlations. RESULTS: For most of the tests in the battery,
      scores from the telephone assessment correlated strongly with those obtained by
      in-person administration of the same tests. Interclass correlations between 0.5
      and 0.8 were observed for tests that assessed attention, memory,
      concentration/working memory, reasoning, and language/crystallized intelligence
      (p < or = 0.05 for each). Interclass correlations for the Hayling Sentence
      Completion test of executive function approached significance (p = 0.09). All
      telephone tests were completed within one hour. CONCLUSION: Administration of
      this neurocognitive test battery by telephone should facilitate assessment of
      neuropsychological deficits among patients with pulmonary arterial hypertension
      living across broad geographical areas, and may be useful for monitoring changes
      in neurocognitive function in response to PAH-specific therapy or disease
      progression.

PMID- 15850487
TI  - Roy Walford and the immunologic theory of aging.
AB  - Roy Walford died on April 27, 2004, at the age of 79. His contributions to
      gerontological research in such diverse areas as caloric restriction, genetics of
      lifespan, immunosenescence, DNA repair and replicative senescence were truly
      remarkable in their depth and innovation. Significantly, most of the areas that
      he pioneered during his illustrious research career remain the "hot" areas of
      current gerontological research. In this sense, he has achieved the most
      important type of immortality. His death was a major personal and professional
      loss to numerous scientists within the gerontological community. In launching
      this new journal on Immunity and Ageing, it is highly fitting, therefore, to
      remember him on the anniversary of his death by briefly reviewing the
      contributions of Roy Walford to this important facet of gerontology. Indeed, it
      was Roy who actually first coined the commonly used term "immunosenescence".

PMID- 15850488
TI  - Fluorescent proteins as tools to aid protein production.
AB  - Fluorescent proteins are genetically encoded, highly versatile reporters useful
      for monitoring various aspects of recombinant protein production. In addition to
      the widely popular green fluorescent protein (GFP) from Aequorea victoria, a
      variety of other fluorescent proteins have been discovered that display a wide
      range of spectral properties. Synthetic variants have also been developed to
      overcome limitations associated with their wild-type counterparts. Having a large
      repertoire of fluorescent proteins with diverse traits opens new opportunities
      for rapid monitoring and optimization of recombinant protein production.

PMID- 15850489
TI  - GABAA receptor gamma 2 subunit knockdown mice have enhanced anxiety-like behavior
      but unaltered hypnotic response to benzodiazepines.
AB  - BACKGROUND: Gamma-aminobutyric acid type A receptors (GABAA-Rs) are the major
      inhibitory receptors in the mammalian brain and are modulated by a number of
      sedative/hypnotic drugs including benzodiazepines and anesthetics. The
      significance of specific GABAA-Rs subunits with respect to behavior and in vivo
      drug responses is incompletely understood. The gamma2 subunit is highly expressed
      throughout the brain. Global gamma2 knockout mice are insensitive to the hypnotic
      effects of diazepam and die perinatally. Heterozygous gamma2 global knockout mice
      are viable and have increased anxiety-like behaviors. To further investigate the
      role of the gamma2 subunit in behavior and whole animal drug action, we used gene
      targeting to create a novel mouse line with attenuated gamma2 expression, i.e.,
      gamma2 knockdown mice. RESULTS: Knockdown mice were created by inserting a
      neomycin resistance cassette into intron 8 of the gamma2 gene. Knockdown mice, on
      average, showed a 65% reduction of gamma2 subunit mRNA compared to controls;
      however gamma2 gene expression was highly variable in these mice, ranging from 10
      95% of normal. Immunohistochemical studies demonstrated that gamma2 protein
      levels were also variably reduced. Pharmacological studies using autoradiography
      on frozen brain sections demonstrated that binding of the benzodiazepine site
      ligand Ro15-4513 was decreased in mutant mice compared to controls. Behaviorally,
      knockdown mice displayed enhanced anxiety-like behaviors on the elevated plus
      maze and forced novelty exploration tests. Surprisingly, mutant mice had an
      unaltered response to hypnotic doses of the benzodiazepine site ligands diazepam,
      midazolam and zolpidem as well as ethanol and pentobarbital. Lastly, we
      demonstrated that the gamma2 knockdown mouse line can be used to create gamma2
      global knockout mice by crossing to a general deleter cre-expressing mouse line.
      CONCLUSION: We conclude that: 1) insertion of a neomycin resistance gene into
      intron 8 of the gamma2 gene variably reduced the amount of gamma2, and that 2)
      attenuated expression of gamma2 increased anxiety-like behaviors but did not lead
      to differences in the hypnotic response to benzodiazepine site ligands. This
      suggests that reduced synaptic inhibition can lead to a phenotype of increased
      anxiety-like behavior. In contrast, normal drug effects can be maintained despite
      a dramatic reduction in GABAA-R targets.

PMID- 15850490
TI  - Intracellular localization of Crimean-Congo Hemorrhagic Fever (CCHF) virus
      glycoproteins.
AB  - BACKGROUND: Crimean-Congo Hemorrhagic Fever virus (CCHFV), a member of the genus
      Nairovirus, family Bunyaviridae, is a tick-borne pathogen causing severe disease
      in humans. To better understand the CCHFV life cycle and explore potential
      intervention strategies, we studied the biosynthesis and intracellular targeting
      of the glycoproteins, which are encoded by the M genome segment. RESULTS:
      Following determination of the complete genome sequence of the CCHFV reference
      strain IbAr10200, we generated expression plasmids for the individual expression
      of the glycoproteins GN and GC, using CMV- and chicken beta-actin-driven
      promoters. The cellular localization of recombinantly expressed CCHFV
      glycoproteins was compared to authentic glycoproteins expressed during virus
      infection using indirect immunofluorescence assays, subcellular
      fractionation/western blot assays and confocal microscopy. To further elucidate
      potential intracellular targeting/retention signals of the two glycoproteins, GFP
      fusion proteins containing different parts of the CCHFV glycoprotein were
      analyzed for their intracellular targeting. The N-terminal glycoprotein GN
      localized to the Golgi complex, a process mediated by retention/targeting
      signal(s) in the cytoplasmic domain and ectodomain of this protein. In contrast,
      the C-terminal glycoprotein GC remained in the endoplasmic reticulum but could be
      rescued into the Golgi complex by co-expression of GN. CONCLUSION: The data are
      consistent with the intracellular targeting of most bunyavirus glycoproteins and
      support the general model for assembly and budding of bunyavirus particles in the
      Golgi compartment.

PMID- 15850491
TI  - Redefinition of Affymetrix probe sets by sequence overlap with cDNA microarray
      probes reduces cross-platform inconsistencies in cancer-associated gene
      expression measurements.
AB  - BACKGROUND: Comparison of data produced on different microarray platforms often
      shows surprising discordance. It is not clear whether this discrepancy is caused
      by noisy data or by improper probe matching between platforms. We investigated
      whether the significant level of inconsistency between results produced by
      alternative gene expression microarray platforms could be reduced by stringent
      sequence matching of microarray probes. We mapped the short oligo probes of the
      Affymetrix platform onto cDNA clones of the Stanford microarray platform.
      Affymetrix probes were reassigned to redefined probe sets if they mapped to the
      same cDNA clone sequence, regardless of the original manufacturer-defined
      grouping. The NCI-60 gene expression profiles produced by Affymetrix HuFL
      platform were recalculated using these redefined probe sets and compared to
      previously published cDNA measurements of the same panel of RNA samples. RESULTS:
      The redefined probe sets displayed a substantially higher level of cross-platform
      consistency at the level of gene correlation, cell line correlation and
      unsupervised hierarchical clustering. The same strategy allowed an almost
      complete correspondence of breast cancer subtype classification between
      Affymetrix gene chip and cDNA microarray derived gene expression data, and gave
      an increased level of similarity between normal lung derived gene expression
      profiles using the two technologies. In total, two Affymetrix gene-chip platforms
      were remapped to three cDNA platforms in the various cross-platform analyses,
      resulting in improved concordance in each case. CONCLUSION: We have shown that
      probes which target overlapping transcript sequence regions on cDNA microarrays
      and Affymetrix gene-chips exhibit a greater level of concordance than the
      corresponding Unigene or sequence matched features. This method will be useful
      for the integrated analysis of gene expression data generated by multiple
      disparate measurement platforms.

PMID- 15850492
TI  - XLMR in MRX families 29, 32, 33 and 38 results from the dup24 mutation in the ARX
      (Aristaless related homeobox) gene.
AB  - BACKGROUND: X-linked mental retardation (XLMR) is the leading cause of mental
      retardation in males. Mutations in the ARX gene in Xp22.1 have been found in
      numerous families with both nonsyndromic and syndromic XLMR. The most frequent
      mutation in this gene is a 24 bp duplication in exon 2. Based on this fact, a
      panel of XLMR families linked to Xp22 was tested for this particular ARX
      mutation. METHODS: Genomic DNA from XLMR families linked to Xp22.1 was amplified
      for exon 2 in ARX using a Cy5 labeled primer pair. The resulting amplicons were
      sized using the ALFexpress automated sequencer. RESULTS: A panel of 11 families
      with X-linked mental retardation was screened for the ARX 24dup mutation. Four
      nonsyndromic XLMR families - MRX29, MRX32, MRX33 and MRX38 - were found to have
      this particular gene mutation. CONCLUSION: We have identified 4 additional XLMR
      families with the ARX dup24 mutation from a panel of 11 XLMR families linked to
      Xp22.1. This finding makes the ARX dup24 mutation the most common mutation in
      nonsyndromic XLMR families linked to Xp22.1. As this mutation can be readily
      tested for using an automated sequencer, screening should be considered for any
      male with nonsyndromic MR of unknown etiology.

PMID- 15850493
TI  - S-nitrosothiols modulate G protein-coupled receptor signaling in a reversible and
      highly receptor-specific manner.
AB  - BACKGROUND: Recent studies indicate that the G protein-coupled receptor (GPCR)
      signaling machinery can serve as a direct target of reactive oxygen species,
      including nitric oxide (NO) and S-nitrosothiols (RSNOs). To gain a broader view
      into the way that receptor-dependent G protein activation -- an early step in
      signal transduction -- might be affected by RSNOs, we have studied several
      receptors coupling to the Gi family of G proteins in their native cellular
      environment using the powerful functional approach of [35S]GTPgammaS
      autoradiography with brain cryostat sections in combination with classical G
      protein activation assays. RESULTS: We demonstrate that RSNOs, like S
      nitrosoglutathione (GSNO) and S-nitrosocysteine (CysNO), can modulate GPCR
      signaling via reversible, thiol-sensitive mechanisms probably involving S
      nitrosylation. RSNOs are capable of very targeted regulation, as they potentiate
      the signaling of some receptors (exemplified by the M2/M4 muscarinic cholinergic
      receptors), inhibit others (P2Y12 purinergic, LPA1lysophosphatidic acid, and
      cannabinoid CB1 receptors), but may only marginally affect signaling of others,
      such as adenosine A1, mu-opioid, and opiate related receptors. Amplification of
      M2/M4 muscarinic responses is explained by an accelerated rate of guanine
      nucleotide exchange, as well as an increased number of high-affinity
      [35S]GTPgammaS binding sites available for the agonist-activated receptor. GSNO
      amplified human M4 receptor signaling also under heterologous expression in CHO
      cells, but the effect diminished with increasing constitutive receptor activity.
      RSNOs markedly inhibited P2Y12 receptor signaling in native tissues (rat brain
      and human platelets), but failed to affect human P2Y12 receptor signaling under
      heterologous expression in CHO cells, indicating that the native cellular
      signaling partners, rather than the P2Y12 receptor protein, act as a molecular
      target for this action. CONCLUSION: These in vitro studies show for the first
      time in a broader general context that RSNOs are capable of modulating GPCR
      signaling in a reversible and highly receptor-specific manner. Given that the
      enzymatic machinery responsible for endogenous NO production is located in close
      proximity with the GPCR signaling complex, especially with that for several
      receptors whose signaling is shown here to be modulated by exogenous RSNOs, our
      data suggest that GPCR signaling in vivo is likely to be subject to substantial,
      and highly receptor-specific modulation by NO-derived RSNOs.

PMID- 15850494
TI  - Association of current smoking with airway inflammation in chronic obstructive
      pulmonary disease and asymptomatic smokers.
AB  - BACKGROUND: Inflammation in the airways and lung parenchyma underlies fixed
      airway obstruction in chronic obstructive pulmonary disease. The exact role of
      smoking as promoting factor of inflammation in chronic obstructive pulmonary
      disease is not clear, partly because studies often do not distinguish between
      current and ex-smokers. METHODS: We investigated airway inflammation in sputum
      and bronchial biopsies of 34 smokers with chronic obstructive pulmonary disease
      (9 Global initiative for Chronic Obstructive Lung Disease stage 0, 9 stage I, 10
      stage II and 6 stage III) and 26 asymptomatic smokers, and its relationship with
      past and present smoking habits and airway obstruction. RESULTS: Neutrophil
      percentage, interleukin-8 and eosinophilic-cationic-protein levels in sputum were
      higher in chronic obstructive pulmonary disease (stage I-III) than asymptomatic
      smokers. Inflammatory cell numbers in bronchial biopsies were similar in both
      groups. Current smoking correlated positively with macrophages: in bronchial
      biopsies in both groups, and in sputum in chronic obstructive pulmonary disease.
      Pack-years smoking correlated positively with biopsy macrophages only in chronic
      obstructive pulmonary disease. CONCLUSION: Inflammatory effects of current
      smoking may mask the underlying ongoing inflammatory process pertinent to chronic
      obstructive pulmonary disease. This may have implications for future studies,
      which should avoid including mixed populations of smokers and ex-smokers.

PMID- 15850495
TI  - Characterisation of the genomic architecture of human chromosome 17q and
      evaluation of different methods for haplotype block definition.
AB  - BACKGROUND: The selection of markers in association studies can be informed
      through the use of haplotype blocks. Recent reports have determined the genomic
      architecture of chromosomal segments through different haplotype block
      definitions based on linkage disequilibrium (LD) measures or haplotype diversity
      criteria. The relative applicability of distinct block definitions to association
      studies, however, remains unclear. We compared different block definitions in 6.1
      Mb of chromosome 17q in 189 unrelated healthy individuals. Using 137 single
      nucleotide polymorphisms (SNPs), at a median spacing of 15.5 kb, we constructed
      haplotype block maps using published methods and additional methods we have
      developed. Haplotype tagging SNPs (htSNPs) were identified for each map. RESULTS:
      Blocks were found to be shorter and coverage of the region limited with methods
      based on LD measures, compared to the method based on haplotype diversity.
      Although the distribution of blocks was highly variable, the number of SNPs that
      needed to be typed in order to capture the maximum number of haplotypes was
      consistent. CONCLUSION: For the marker spacing used in this study, choice of
      block definition is not important when used as an initial screen of the region to
      identify htSNPs. However, choice of block definition has consequences for the
      downstream interpretation of association study results.

PMID- 15850496
TI  - Posttraumatic stress disorder: an exploratory study examining rates of trauma and
      PTSD and its effect on client outcomes in community mental health.
AB  - BACKGROUND: Rates of trauma and Posttraumatic Stress Disorder (PTSD) were
      examined in order to compare the profile in clients of an Australian Public
      Mental Health Service with that reported in the international literature for
      clients with major mental illness and to explore the effect of this on client
      health outcomes. Potential factors contributing to increased levels of
      trauma/PTSD in this group of clients and the issue of causality between PTSD and
      subsequent mental illness was also explored. METHODS: A convenience sample of 29
      clients was screened for trauma and PTSD using the Posttraumatic Stress
      Diagnostic Scale (PDS) and selected outcome measures. Paired and independent
      samples t-test and ANOVA were applied to the data. RESULTS: High levels of
      undocumented trauma and PTSD were found. Twenty clients, (74%) reported exposure
      to multiple traumatic events; 33.3% (9) met DSM IV diagnostic criteria for PTSD.
      Significant difference was found for PTSD symptomatology, severity and impairment
      and for client and clinician-rated scores of Quality of Life (QOL) outcomes in
      the PTSD group. No effect for PTSD symptomatology on the Working Alliance (WA)
      was found. Factors that may influence higher rates of PTSD in this group were
      identified and included issues associated with the population studied, the
      predominance of assaultive violence found, and vulnerability and risks factors
      associated with re-traumatisation within the social and treating environments.
      CONCLUSION: A similar trauma and PTSD profile to that reported in the
      international literature, including greater levels of trauma and PTSD and a
      poorer QOL, was found in this small sample of clients. It is postulated that the
      increased levels of trauma/PTSD as reported for persons with major mental
      illness, including those found in the current study, are primarily related to the
      characteristics of the population that access public mainstream psychiatric
      services and that these factors have specific implications for service delivery,
      and raise issues of efficiency and effectiveness of resource use in achieving
      successful outcomes in public mental health services for clients with co-morbid
      PTSD. Further research with a more rigorous design is needed to test these
      preliminary findings within Australian Community Mental Health Services.

PMID- 15850497
TI  - The effect of glucosamine sulphate on osteoarthritis: design of a long-term
      randomised clinical trial [ISRCTN54513166].
AB  - BACKGROUND: Pharmacological treatment for osteoarthritis (OA) can be divided into
      two groups: symptom-modifying drugs and disease-modifying drugs. Symptom
      modifying drugs are currently the prescription of choice for patients with OA, as
      disease-modifying drugs are not yet available in usual care. However, there has
      recently been a lot of debate about glucosamine sulphate (GS), a biological agent
      that is thought to have both symptom-modifying and disease-modifying properties.
      This assumption has yet to be proved. The objective of this article is to present
      the design of a blind randomised clinical trial that examines the long-term
      symptom-modifying and disease-modifying effectiveness of GS in patients with hip
      OA. This trial is ongoing and will finish in March 2006. METHODS/DESIGN: Patients
      with hip OA meeting the ACR-criteria are randomly allocated to either 1500 mg of
      oral GS or placebo for the duration of two years. The primary outcome measures,
      which are joint space narrowing (JSN), and change in the pain and function score
      of the Western Ontario McMaster Universities Osteoarthritis index (WOMAC), are
      determined at baseline and after two years of follow-up during the final
      assessment. Intermediate measures at three-month intervals throughout the trial
      are used to study secondary outcome measures. Secondary outcome measures are
      changes in WOMAC stiffness score, quality of life, medical consumption, side
      effects and differences in biomarker CTX-II.

PMID- 15850498
TI  - Focus on the clinical ramifications of antipsychotic choice for the risk for
      developing type 2 diabetes mellitus.

PMID- 15850499
TI  - Effects of isradipine, a dihydropyridine-class calcium-channel antagonist, on d
      methamphetamine's subjective and reinforcing effects.
AB  - In healthy human volunteers, we have previously shown that isradipine, a
      dihydropyridine-class calcium-channel antagonist, reduces some methamphetamine
      induced positive subjective effects associated with its abuse liability,
      presumably by antagonizing cortico-mesolimbic dopamine pathways. In the present
      study, we combined acute immediate-release (IR) isradipine with repeated
      sustained-release (SR) isradipine pretreatment to determine whether isradipine
      could antagonize methamphetamine's positive subjective and reinforcing effects in
      methamphetamine-dependent research subjects. We included 18 non-treatment
      seeking, methamphetamine-dependent subjects aged between 18 and 51 years in this
      double-blind, within-subject, cross-over study, which was done in a human
      laboratory. Intravenous methamphetamine (0, 15 and 30 mg) was administered on
      three different days after 5 days of double-blind cross-over treatment with
      either isradipine or matching placebo. Subjects received oral isradipine 30 mg SR
      at bedtime, plus 15 mg IR administered 2 h before methamphetamine infusion. Self
      report questionnaires measured drug liking, euphoria, craving, stimulation, and
      methamphetamine preference. Methamphetamine reinforcement was measured by a
      behavioural procedure involving choices between methamphetamine and money. For
      those who received isradipine second and placebo first as the pretreatment
      paradigm but not vice versa, methamphetamine-induced drug liking, elation, and
      preference were reduced significantly by isradipine. Depending upon conditioning
      status, isradipine can reduce some methamphetamine-induced positive subjective
      and reinforcing effects associated with its abuse liability in methamphetamine
      addicts.

PMID- 15850500
TI  - Association between three functional polymorphisms of the dopamine D2 receptor
      gene and polydipsia in schizophrenia.
AB  - The underlying pathophysiology of polydipsia in schizophrenia is poorly
      understood. However, several studies suggest there may be a genetic
      predisposition to polydipsia, including our previous study demonstrating familial
      concordance of polydipsia among first-degree relatives with schizophrenia.
      Antipsychotic medications may contribute to the development of polydipsia and
      studies show that dopamine D2 receptors are involved in drinking behaviour
      pathophysiology. Our hypothesis is that polymorphisms in the dopamine D2 receptor
      gene (DRD2) may confer susceptibility to polydipsia in schizophrenia. We tested
      for an association between polydipsia in schizophrenia and three functional
      polymorphisms of DRD2. The three polymorphisms, -141C Ins/Del, Ser311Cys, and
      TaqIA, were genotyped in patients with polydipsia (n = 64) and in those without
      polydipsia (n = 91). Of the three polymorphisms, TaqIA was significantly
      associated with polydipsia [genotype: chi2 = 6.59, df = 2, p = 0.037; allele:
      chi2 = 6.52, df = 1, p = 0.011, OR 1.81, 95% CI 1.15-2.86]. Haplotype analysis of
      the three markers found increased significance of the association (global, p =
      0.00091). Although based on a relatively small portion of the sample, individual
      comparison of the common haplotypes showed that haplotype Ins-Cys-A1 was
      significantly less frequent in patients with polydipsia (p = 0.00082). The
      present data suggests polymorphisms in DRD2 may confer susceptibility to
      polydipsia in schizophrenia. To confirm our findings, further studies are
      warranted on larger samples using more extensive biological measures for
      diagnosing the polydipsia phenotype.

PMID- 15850501
TI  - Low doses of lithium carbonate reduce melatonin light sensitivity in healthy
      volunteers.
AB  - Sensitivity of the pineal hormone melatonin to bright light at night has been
      posited as a putative marker of affective disorders. Research demonstrates
      melatonin supersensitivity to light in bipolar disorder, however the role that
      lithium carbonate plays in this response is unclear. This study assessed the
      effect of lithium on nocturnal melatonin secretion and sensitivity to light in
      healthy adults. Ten participants, tested on two nights, had blood samples drawn
      between 20:00 and 02:30 hours. On testing nights participants were exposed to 200
      lux of light between 24:00 and 01:00 hours. Participants took 250 mg of lithium
      daily for 5 d between testing nights. The results indicated that lithium had a
      significant effect on sensitivity to light but not on overall melatonin
      synthesis. This finding has implications on the true magnitude of the melatonin
      light response in people with bipolar disorder and may elucidate possible
      mechanisms of action of lithium.

PMID- 15850502
TI  - Naltrexone for the treatment of alcoholism: a meta-analysis of randomized
      controlled trials.
AB  - Many trials of naltrexone have been carried out in alcohol-dependent patients.
      This paper is aimed to systematically review its benefits, adverse effects, and
      discontinuation of treatment. We assessed and extracted the data of double-blind,
      randomized controlled trials (RCTs) comparing naltrexone with placebo or other
      treatment in people with alcoholism. Two primary outcomes were subjects who
      relapsed (including heavy drinking) and those who returned to drinking. Secondary
      outcomes were time to first drink, drinking days, number of standard drinks for a
      defined period, and craving. All outcomes were reported for the short, medium,
      and long term. Five common adverse effects and dropout rates in short-term
      treatment were also examined. A total of 2861 subjects in 24 RCTs presented in 32
      papers were included. For short-term treatment, naltrexone significantly
      decreased relapses [relative risk (RR) 0.64, 95% confidence interval (CI) 0.51
      0.82], but not return to drinking (RR 0.91, 95% CI 0.81-1.02). Short-term
      treatment of naltrexone significantly increased nausea, dizziness, and fatigue in
      comparison to placebo [RRs (95% CIs) 2.14 (1.61-2.83), 2.09 (1.28-3.39), and 1.35
      (1.04-1.75)]. Naltrexone administration did not significantly diminish short-term
      discontinuation of treatment (RR 0.85, 95% CI 0.70-1.01). Naltrexone should be
      accepted as a short-term treatment for alcoholism. As yet, we do not know the
      appropriate duration of treatment continuation in an alcohol-dependent patient
      who responds to short-term naltrexone administration. To ensure that the real
      world treatment is as effective as the research findings, a form of psychosocial
      therapy should be concomitantly given to all alcohol-dependent patients receiving
      naltrexone administration.

PMID- 15850503
TI  - A case of delayed galactorrhoea as an adverse event of overlapping haloperidol
      and clozapine administration.

PMID- 15850506
TI  - [Identification and analysis of a mouse gene homologous to human hepatitis B
      virus pre-S1 protein-binding protein using the bioinformatics method].
AB  - OBJECTIVE: To clone and identify the mouse gene homologous to human hepatitis B
      virus (HBV) pre-S1 protein-binding protein (PS1BP). METHODS: The human PS1BP cDNA
      sequence was used as the reference sequence to search homologous mouse cDNA
      sequence from GenBank established by National Center for Biotechnology (NCBI),
      National Institute of Health (NIH), for its homologous cDNA sequences of mouse by
      BLASTn tool. The characteristics of mouse PS1BP protein primary structure were
      predicted by online software. Finally the genomic DNA structure of mouse PS1BP
      was deduced and compared. RESULTS: The mouse PS1BP was identified and consisted
      of 1455 nt, coding a protein of 484 aa. The identity of human and mouse PS1BP
      protein is 84.92% (411/484). The genomic DNA of mouse PS1BP consisted of 3 exons
      and 2 introns. CONCLUSION: The identification and characterization of mouse PS1BP
      cDNA and genomic DNA pave a way for further study of their structures and
      functions.

PMID- 15850507
TI  - [Screening of HBeAgTP interacting proteins in hepatocytes with yeast-two hybrid
      technique].
AB  - OBJECTIVE: To screen proteins in hepatocytes interacting with HBeAg
      transactivated protein (HBeAgTP) with yeast-two hybrid technique for
      investigating the biological functions of HBeAgTP. METHODS: Suppression
      subtractive hybridization (SSH) and bioinformatics techniques were used for
      screening and cloning of the target genes transactivated by HBeAg. The HBeAgTP
      gene was amplified by polymerase chain reaction (PCR) and HBeAgTP bait plasmid
      was constructed with yeast-two hybrid system 3, and then transformed into yeast
      AH109. The transformed yeast mated with yeast Y187 containing liver cDNA library
      plasmid in 2 x YPDA medium. Diploid yeast was plated on synthetic dropout
      nutrient medium (SD/-Trp-Leu-His-Ade) and synthetic dropout nutrient medium (SD/
      Trp-Leu-His-Ade) containing X-gal for selecting two times and screening. After
      extracting and sequencing of plasmid from blue colonies, the results were
      analyzed by bioinformatics. RESULTS: HBeAgTP gene was successfully cloned and
      expressed in yeast cells. Fifteen genes in twenty-four positive colonies were
      obtained using yeast-two hybrid technique. CONCLUSION: HBeAgTP conjugated protein
      genes were successfully cloned, along with the genes involved in transcription
      and translation of proteins, immunoloregulation, materials and energy metabolism
      in vivo.

PMID- 15850508
TI  - [Analysis of prognosis on patients with severe viral hepatitis using the model
      for end-stage liver disease].
AB  - OBJECTIVE: To study the practical use of the model for end-stage liver disease
      (MELD) in clinics and to assess its validity in predicting the prognoses of
      patients with severe viral hepatitis and to determine the validity of the model
      by the concordance (c)-statistic which is equivalent to the area under the
      receiver operating characteristic (ROC) curve. Also, the optimal cutoff values of
      MELD to discriminate between deceased and surviving patients were calculated
      using ROC curves. METHODS: 121 patients were divided into a plasma exchange (PE)
      group and a non-plasma exchange (non-PE) group, and they were graded with the
      MELD formula. The death rate was observed within three months. RESULTS: 81
      patients died within 3 months (35 cases in the PE group, 46 cases in the non-PE
      group). The mortality rates of patients in the PE group whose MELD scores were
      between 20 to 30 and 30 to 40 were 31.6% and 57.7% respectively, but in non-PE
      cases they were 67.6%, 81.3% respectively; there was a significant difference
      between the PE group and non-PE group. The mortality rates of patients whose MELD
      score was higher than 40 were 93.3% in the PE group and 100% in the non-PE group,
      however there was no significant difference between the two groups. The optimal
      cut-off values of MELD to predict the prognoses of patients were 30 in the PE
      group whose sensitivity, specificity and c-statistic were 80.0%, 52.0% and 0.777,
      but in the non-PE group they were 25, 82.6%, 86.7% and 0.869, respectively.
      CONCLUSIONS: This study suggests that MELD scores can serve as an index of the
      severity of the disease of patients with severe viral hepatitis, and that the
      mortality rates of the patients increase with the increase of their MELD scores.
      MELD can accurately predict the short-term prognoses of patients with severe
      viral hepatitis.

PMID- 15850509
TI  - [Anti-HBV effect of fusion protein (TA1-IFN) in vitro].
AB  - OBJECTIVE: To investigate the anti-HBV effect of fusion protein thymosin alpha1
      interferon alpha (TA1-IFN) in vitro and to compare its effect with a combination
      of interferon alpha and thymosin alpha1. METHODS: After 2.2.15 cells were seeded
      for 24 hours, drugs of five serial concentrations (8000, 4000, 2000, 1000, 500
      U/ml) were added to the wells, then the medium was changed every three days.
      After 2.2.15 cells were treated with drugs for 6 days, the medium was collected.
      The inhibitory rates on HBsAg and HBeAg were determined using Abbot kit, and the
      cytotoxicity of different drugs by means of MTT colorimetric assays was also
      observed. RESULTS: The inhibitory rate of fusion protein on HBsAg, HBeAg was dose
      dependent and reached the maximum at 8000 U/ml concentration. In the meantime,
      the inhibitory rates of fusion protein on HBsAg and HBeAg were 72.2% +/- 0.8% and
      60.4% +/- 1.1% respectively, and the cell survival rate was 85.2% +/- 2.0%; In
      the corresponding concentration, the inhibitory rates of combination thymosin
      alpha 1 and interferon alpha on HBsAg and HBeAg were 40.0% +/- 0.7%, 34.5% +/-
      3.2% respectively. The results showed significant statistical differences between
      them; cell survival rate 70.0% +/- 1.9%, and the difference of the results was
      also significant. Cytotoxicity of fusion protein was weaker than a combination of
      thymosin alpha 1 and interferon alpha. CONCLUSION: Fusion protein TA1-IFN exerted
      stronger anti-HBV effects in vitro. Its anti-HBV effects in vitro were stronger
      than the combination of thymosin alpha and interferon alpha, and its cytotoxicity
      was weaker than the combination of thymosin alpha and interferon alpha. Our
      studies provided important evidence for clinical research on TA1-IFN, and also
      brought new hope for hepatitis B therapy.

PMID- 15850510
TI  - [Correlation between signal/cutoff ratios of anti-HCV enzyme immunoassay (EIA)
      and their true positivity in blood donors].
AB  - OBJECTIVES: To evaluate the correlation between signal/cutoff (S/CO) ratios of
      anti-HCV EIA and their true positivity for determining the predictive value of
      S/CO ratios. METHODS: One hundred and fifty-nine samples of blood from donors
      positive for anti-HCV at the initial screening were collected from Beijing,
      Guangzhou, Hangzhou, Kunming and Urumchi. All the samples were retested by Ortho
      and 6 Chinese domestic anti-HCV EIA kits in duplicate, and detected for HCV RNA
      (NAT) using Chiron Procleix HIV/HCV system (transcription mediated amplification,
      TMA). The HCV RNA negative samples were further tested for anti-HCV by Chiron
      RIBA 3.0. Either NAT or RIBA positive samples were interpreted as the true
      positive. RESULTS: All 7 anti-HCV EIA kits had a significant correlation between
      S/CO ratios and true positivity. The S/CO ratio of Ortho > or = 3.8 predicted the
      true positivity in 96.1% of the samples tested. The S/CO ratios of BGI-GBI, GWK,
      SABC, KHB, InTec, and Wantai were > or = 7.0, > or = 10.0, > or = 6.0, > or =
      10.0, > or = 8.6, > or = 14.0 and predicted 96.1%, 96.1%, 97.3%, 96.0%, 96.1%,
      96.0% of the true positivity, respectively. CONCLUSIONS: The S/CO ratios of anti
      HCV EIA kits are associated with the true positivity. S/CO ratios of Ortho, BGI
      GBI, GWK, SABC, KHB, InTec and Wantai predicting > or = 95% true positivity are >
      or = 3.8, > or = 7.0, > or = 10.0, > or = 6.0, > or = 1 0.0, > or = 8.6 and > or
      = 14.0, respectively.

PMID- 15850511
TI  - [Clinical and experimental study of the therapeutic effect of umbilical cord
      blood stem cell transplantation on liver failure and heart damage in severe viral
      hepatitis patients].
AB  - OBJECTIVE: To investigate and compare the therapeutic effect of umbilical cord
      blood stem cell transplantation (UCBSCT) or adult fresh plasma in severe viral
      hepatitis liver failure with/without heart damage, and to study the effect of
      UCBSCT on liver lesions in rats. METHODS: 83 severe hepatitis patients
      with/without heart damage were included in the study between January 1994 and
      June 2003. The patients were treated with UCBSCT or given adult plasma
      transfusions. The therapeutic effect was evaluated by serial determination of
      liver function and myocardium enzymes in all patients before and after the
      treatment. The model of experimental hepatic failure was constructed in SD rats
      by injecting carbon tetrachloride. Then, the rats were given normal saline,
      neonate cord blood serum or neonate cord blood stem cells respectively. The
      expression of human AFP and Alb in SD rat livers was detected by
      immunohistochemistry; and human special DNA was detected by PCR. RESULTS: The
      UCBSCT group had much better effects in the improvement of liver function than
      the adult plasma group had, no matter whether the patients had heart damage or
      not. Moreover, UCBSCT can decrease heart impairment of the patients. The animal
      experiment demonstrated that AFP and Alb positive cells were present in the
      neonate cord blood stem cell group after 21 days and 1 month; human special DNA
      was detected by PCR in these SD rat livers. CONCLUSION: UCBSCT displayed good
      therapeutic effects on severe viral hepatitis and improvement of heart injury of
      the patients. The rat liver immunohistochemistry indicated that neonate cord
      blood stem cell application can decrease the liver damage and increase
      hepatocellular regeneration. Human umbilical cord blood stem cells can
      differentiate into liver cells in acute damaged SD rat livers.

PMID- 15850512
TI  - [A study of the progression of cirrhosis in patients with human immunodeficiency
      virus and hepatitis C virus coinfection].
AB  - OBJECTIVES: To study the progression of cirrhosis in patients with HIV/HCV
      coinfection. METHODS: The patients were divided into two groups, HIV/HCV
      coinfection group (n = 140) and simple HCV infection group (n = 33). A
      retrospective study was designed to compare the development of cirrhosis in a 15
      year period between the two groups. RESULTS: The development of cirrhosis in the
      HIV/HCV coinfection group was higher than that in the simple HCV infection group
      (16.4% vs. 3.0%, P=0.045). Counts of CD4+ T and CD8+ T in the HIV/HCV group were
      200.0+/-134.1 cells/microl and 880.6+/-444.2 cells/microl, respectively. The
      counts of CD4+ T and CD8+ T in the group of simple HCV infection were 752.3+/
      251.7 cells/microl and 529.0+/-170.7 cells/microl, respectively. There were
      significant differences between the two groups regarding the counts of CD4+ T and
      CD8+ T. Comparing the cases of HCV RNA (+) and anti-HCV (+) with the cases of HCV
      RNA (+) and anti-HCV (-), we found that the ratio was 89 to 15 in the group of
      HIV/HCV coinfection, and 25 to 0 in the group of simple HCV infection. The
      difference between the two groups was statistically significant (P = 0.043).
      CONCLUSION: HIV/HCV coinfection can accelerate the progression of cirrhosis,
      which may be due to the effect of HIV on cellular immunity and humoral immunity.

PMID- 15850513
TI  - [Recombinant adenovirus vectors carrying antisense MMP2 inhibit invasion of HCC
      cells in vitro].
AB  - OBJECTIVES: To construct a recombinant adenoviral vector carrying antisense
      matrix metalloproteinase-2 (MMP2) and to study its inhibitory effects on the
      invasiveness and migratory capacity of hepatocellular carcinoma (HCC) cell line
      HepG2 in vitro. METHODS: Total RNA was extracted from HCC. Then a 500 bp fragment
      at the 5' end of the human MMP2 cDNA sequence was synthesized by polymerase chain
      reaction (PCR) and was reversely inserted into the multiclone site (MCS) of the
      shuttle plasmid pAdTrack-CMV. With the resultant plasmid and the backbone plasmid
      pAdEasy-1, the homologous recombination took place in the E.coli BJ5183 and the
      recombinant adenoviral plasmid carrying the antisense MMP2 gene was constructed.
      The adenovirus (Ad-MMP2AS) was packaged and amplified in the HEK 293 cells and
      the viral titer was checked by GFP. Using the Boyden chamber model, the influence
      of Ad-MMP2AS on the invasion ability of HepG2 cells was determined in vitro.
      RESULTS: The recombinant adenovirus vector carrying antisense MMP2 was
      constructed successfully and a strong green fluorescence was observed in HepG2
      cells under a fluorescence microscope. The viral titer was 1 x 10(8); Ad-MMP2AS
      can effectively inhibit the penetrating capacity of HepG2 cells through Matrigel
      in vitro. CONCLUSION: The recombinant adenovirus with antisense MMP2 can
      effectively inhibit the invasiveness and migratory capacity of HepG2 in vitro and
      may have potential in treating HCC.

PMID- 15850514
TI  - [Two-dimensional gel electrophoresis of subcellular fractions of hepatoma cells].
AB  - OBJECTIVES: To seek a better profiling of proteins of hepatoma cells. METHODS:
      The homogenate of hepatoma cells QGY-7703 was fractionated into four parts by
      differential centrifugation: the nuclei, the pellet by 20,000 x g, the pellet by
      100,000 x g and the cytosolic supernatant. The four fractions were submitted to
      two-dimensional gel electrophoresis and their electrophoretic patterns were
      analyzed. RESULTS: In comparison with the protein pattern of hepatoma cells not
      fractionated, the patterns of the four fractions display many more protein spots,
      and a large number of proteins present in the nuclei and cytosolic supernatant
      were not shown in the not-fractionated samples. CONCLUSION: Preparation of
      subcellular fractions before electrophoretic procedures proves to be very useful;
      not only can it improve the results of two-dimensional gel electrophoresis, but
      also can lead to research into the subcellular level.

PMID- 15850515
TI  - [Differentiation of bone marrow derived Thy-1+ beta2M- cells into liver cells in
      AA induced liver injury micro-environment].
AB  - OBJECTIVE: To investigate the differentiation of bone marrow derived Thy-1+
      beta2M- cells (BDTCs) into liver cells in allyl alcohol (AA) induced liver injury
      micro-environment. METHODS: BDTCs of male F344 rats were isolated by two-step
      magnetic separation system (MACS) technique, and infused intraportally into
      female recipients after labeling with PKH26. Thirty recipients were divided
      randomly into 3 groups: (1) AA-injured liver + BDTCs infusion, (2) normal liver +
      BDTCs infusion and (3) AA-injured liver + NS infusion (control). Blood
      biochemical examination, fluorescence labeled cellular localization, Y-chromosome
      sry gene in-situ hybridization and immunohistochemistry were carried out to
      evaluate BDTCs distribution, differentiation and proliferation in recipients's
      livers after different intervals. RESULTS: Fluoromicroscopy and in situ
      hybridization suggested that BDTCs of donors were interspersed in pieces and
      cords among the necro-periportals induced by AA; immunohistochemistry indicated
      that those implanted cells expressed OV-6, AFP, CK19 and albumin successively,
      while positive cells were hardly seen in the normal liver + BDTCs infusion group.
      Compared with the controls, the blood biochemical restitution was more rapid in
      group (1), (9.8 d +/- 3.1 d vs. 13.7 d +/- 4.2 d). CONCLUSION: The injury micro
      environment induced by AA facilitates BDTCs integration with hepatic cell plates
      and differentiation into mature liver cells. BDTCs differentiation into liver
      cells might accelerate endogenous liver cell regeneration and reparation.

PMID- 15850517
TI  - [Expression of glypican-3 mRNA in hepatocellular carcinoma and its significance].

PMID- 15850516
TI  - [Changes in intrahepatic portal systemic shunt flow in a rat model of acute
      intrahepatic presinusoidal portal hypertension].
AB  - OBJECTIVES: To investigate the changes in intrahepatic portal systemic shunt flow
      (IHSF) and their relationship with microspheres induced acute portal
      hypertension. METHODS: Following acute intrahepatic presinusoidal obstruction by
      intraportal injection of 15 microm diameter microspheres in male Wistar rats,
      functional hepatic blood flow (FHBF) and IHSF were determined by hepatic sorbitol
      uptake methods. The percentage of large shunts of diameter > 15 microm were
      estimated by intraportal injection of 51Cr labeled 15 mum diameter microspheres.
      RESULTS: In normal control rats, hepatic sorbitol uptake was 97.9%+/-0.5% and
      IHSF was negligible, with FHBF equaling total hepatic blood flow [(2.52 +/- 0.23)
      ml/min x 100 g body weight-1]. Microsphere injection decreased sorbitol uptake to
      12.8% +/- 4.3% and further to 4.1% +/- 0.7% when followed by hepatic arterial
      ligation. In the latter two groups, IHSF (1.46 +/- 0.15 and 1.16 +/- 0.19 ml/min
      x 100 g body weight-1, respectively) was not significantly different from portal
      venous flow [(1.36 +/- 0.20) and (1.20 +/- 0.20) ml/min x 100 g body weight-1,
      respectively; t = 2.013 and t = 2.116]. Portal venous flow remained at 70% of
      basal values and portal venous pressure only increased by 50% from baseline. 51Cr
      labeled microsphere shunt fraction through large shunts (> 15 microm) was less
      than 1.0%. CONCLUSION: Intrahepatic portasystemic shunts in the normal rat liver
      predominantly have diameters less than 15 microm and, when activated by
      intraportal injection of microspheres, they divert up to 70% of portal venous
      blood flow away from hepatic sinusoids and thereby they reduce acute increases in
      portal venous pressure.

PMID- 15850518
TI  - [The role of CXCL16 in immunological liver injury induced by BCG and LPS in
      mice].
AB  - OBJECTIVE: To investigate the pathophysiological role of CXCL16 in immunological
      liver injury induced by Bacille de Calmette et Guerin (BCG) and
      lipopolysaccharides (LPS). METHODS: Immunological liver injury was induced by BCG
      and LPS in mice, and the expression of CXCL16 was detected in the liver tissues
      by real-time quantitative PCR and immunohistochemical examination. The
      relationship of the expression of CXCL16 and the extent of hepatic necrosis was
      investigated histopathologically and immunohistochemically. Mononuclear cells
      were isolated from the liver tissues and their numbers were counted; T
      lymphocytes populations in the liver tissue were also analyzed with FACS.
      RESULTS: The immunological liver injury model was successfully created. Up
      regulation of CXCL16 in injured livers correlated with the extent of liver injury
      and the amountmononuclear cell infiltrations. CONCLUSION: These findings suggest
      that up-regulation of CXCL16 was closely correlated with liver injury extent
      during the immunological liver injury induced by BCG-LPS in mice, and
      intrahepatic recruitment of specific lymphocytes might be an important mechanism
      of liver injury.

PMID- 15850519
TI  - [Bcl-xl blocks tumor necrosis factor alpha-induced caspase 8 activation and
      apoptosis].
AB  - OBJECTIVE: To explore the effect of Bcl-xl on tumor necrosis factor-alpha
      (TNFalpha)-induced apoptosis signal pathway and apoptosis. METHODS: A dominant
      negative mutant of ikB (pmi kappaB) and Green Fluorescent Protein (GFP)
      expression plasmid pEGFP-C1, pmi kappab and pEGFP-C1 and Bcl-xl expression
      construct pBcl-xl/HA, were co-transfected into HeLa cells. Expression plasmid
      pBcl-xl/HA was introduced into p65-/-MEF cells in which nuclear factor-kappaB (NF
      kappaB)/p65 was deficient, to establish cell line p65-/-Bcl-xl expressing Bcl-xl
      by selection with puromycin. These cells were treated with TNFalpha at a
      concentration of 10 ng/ml, and apoptotic cell death was examined microscopically
      with trypan blue staining. The proteins were abstracted from treated cells, and
      caspase 8 activation and cleavage of poly (ADP-ribose) polymerase (PARP) were
      examined by western blot using a specific antibody that recognized cleaved
      caspase 8 and cleaved PARP, respectively. RESULTS: HeLa cells transfected with
      pmi kappaB, TNFalpha showed significant cell death as they became rounded,
      shrank, and detached. However in HeLa cells co-transfected with pBcl-xl and pmi
      kappaB, no cell death was observed after treatment with TNFalpha. In p65-/- MEF
      cells; cell death was observed at 4 hours after treatment with TNFalpha, and cell
      death reached 90% at 12 hours after the treatment. However, in p65-/-Bcl-xl/HA
      cells expressing Bcl-xl, no cell death was seen even when treated with TNFa for
      24 hours. Meanwhile, in pmikB/HeLa cells transfected with pmi kappaB, TNFalpha
      induced caspase 8 activation and PARP cleavage, but in the HeLa cells co
      transfected with pBcl-xl and pmi kappaB, no activated caspase 8 and cleaved PARP
      were observed after treatment with TNFalpha. CONCLUSION: In the experimental
      system in which NF-kB was inhibited, Bcl-xl blocked TNFalpha-induced apoptosis
      signal pathway and apoptosis. These results bring to light that further studies
      of the pathogenesis and therapy of TNFa-related diseases are needed.

PMID- 15850520
TI  - [Tumor necrosis factor alpha and enterocyte apoptosis in mice with fulminant
      hepatic failure].
AB  - OBJECTIVE: To study the role of tumor necrosis factor-alpha (TNFalpha) on
      enterocyte apoptosis in the experimental model of fulminant hepatic failure
      (FHF). METHODS: Liver damage was induced by lipopolysaccharide (LPS)/TNFalpha in
      D-galactosamine (GalN) sensitized BALB/c mice. Serum TNFalpha levels were
      determined by enzyme-linked immunosorbent assays (ELISA). The intestinal tissues
      were studied micro- and ultra-microscopically at 2 h, 6 h, 9 h, 12 h and 24 h
      time points in mice with fulminant hepatic failure. Enterocyte apoptosis was
      determined by TUNEL method. The TNFR I expression in the intestinal tissue was
      tested by immunohistochemistry. RESULTS: (1) Gut mucosa was morphologically
      normal at every time point in all groups, but typical apoptotic cells could be
      seen in the experimental groups under the electron microscope. Apoptosis rate of
      gut mucosal epithelial cells was significantly increased at 6 h (large intestine:
      6.47e(-3)+/-2.91e(-4); small intestine: 6.64e(-3)+/-3.78e(-4)), 9 h (large
      intestine: 6.81e(+4)+/-7.41e(+3); small intestine: 2.58e(+4)+/-2.28e(+3)) and 12
      h (large intestine: 4.92e(+4)+/-9.80e(+3); small intestine: 5.24e(+4)+/
      3.01e(+3)), and peaked at 12 h in mice with FHF. (2) TNFalpha induced apoptosis
      of enterocytes in mice with FHF. Anti-TNFalpha inhibited this effect. (3) The
      integrated OD (IOD) levels of TNFalpha receptor I protein expressed differently
      in the intestine of mice with GalN/LPS and GalN/ TNFalpha-induced FHF at 9 h
      after GalN/LPS and GalN/ TNFalpha administration, in comparison with those of the
      control groups. IOD level of TNFRI changed significantly at 6 h (large intestine:
      2.82e(+4)+/-4.60e(+3); small intestine: 1.14e(+4)+/-2.13e(+3)), 9 h (large
      intestine: 6.81e(+4)+/-7.41e(+3); small intestine: 2.58e(+4)+/-2.28e(+3)) and 12
      (large intestine: 4.92e(+4)+/-9.80e(+3); small intestine: 5.24e(+4)+/-3.01e(+3))
      hours after GalN/LPS and GalN/ TNFa administration. The expression of TNFR1
      protein was significantly higher at 9 and 12 h after GalN/LPS and GalN/TNFa
      administration than other time points. Protein expression of TNFR1 was positively
      correlated with enterocyte apoptosis. CONCLUSION: TNFa can induce enterocyte
      apoptosis in mice with FHF. Anti- TNFalpha IgG can inhibit this role. Excessive
      TNFRI expression of enterocyte in fulminant hepatic failure can be induced by
      TNFa, which suggests that TNFalpha can induce apoptosis of enterocyte by up
      regulation of TNFRI protein expression.

PMID- 15850521
TI  - [Evaluation of the effects of dense endoscopic ligation for bleeding esophageal
      varices].
AB  - OBJECTIVE: To evaluate the short-term and long-term effects of dense endoscopic
      variceal ligation (DEVL) for bleeding esophageal varices. METHODS: Patients with
      acute or with a history of esophageal variceal bleeding underwent regular DEVLs
      with a 2-3 week interval between 2 sessions until their varices disappeared at
      the lower 5-6 cm part of the esophagus. Follow-up study and gastroscopy were
      performed at 3, 6 and 12 months after the final DEVL in all patients. The results
      at 3 months were classified as short-term effects and those after 6 months as
      long-term ones. RESULTS: 126 patients underwent DEVLs with 403 sessions and 3641
      ligations; each patient was ligated with a mean of 3.2 sessions and at 28.9
      points. The cure rate of acute variceal bleeding was 100.0%; short-term rate of
      variceal eradication was 94.4% and variceal rebleeding occurred in 3.9% patients.
      After a mean of 22.3 months follow-up period, the recurrence of esophageal
      varices was observed in 11.9% patients, but the variceal rebleeding rate was only
      3.2% and no patients died from it. CONCLUSION: DEVL was very useful and effective
      in both short-term and long-term variceal eradication and prevention of variceal
      rebleeding.

PMID- 15850522
TI  - [A long-term observation and follow-up for patients with HBeAg/Anti-HBe
      seroconversion after lamivudine treatment].
AB  - OBJECTIVE: To observe the resulting change in patients who achieved HBeAg/Anti
      HBe seroconversion after lamivudine treatment. METHODS: 68 patients were observed
      for over 24 months. They were HBeAg/Anti-HBe with a seroconversion time > or = 6
      months and the course of lamivudine treatment was > or = 18 months. RESULTS:
      After lamivudine treatment, the rate of HBeAg/Anti-HBe seroconversion was 25.19%,
      the rate of YMDD mutations was 20.59%, and the rate of relapse was 27.94% for
      these patients that achieved HBeAg/Anti-HBe seroconversion in observation and in
      the follow-up period. Lamivudine was still an effective drug for these patients
      with relapses. The rate of relapse was in correlation to the patients' age and
      the ALT level before treatment. The rate of relapse was not correlated to the HBV
      DNA level before the course of treatment. YMDD mutations were not correlated to
      the relapses. CONCLUSION: Even with a HBeAg/Anti-HBe seroconversion time > or = 6
      months, the rate of relapse was still higher in patients with chronic hepatitis B
      that received lamivudine. The patients with long-term lamivudine treatment should
      be observed and have frequent follow-up visits.

PMID- 15850523
TI  - [Characteristics of SV40-mediated immortalized human hepatocytes].

PMID- 15850524
TI  - [Treatment of chronic hepatitis C with peginterferon alpha-2a and the factors
      influencing the effect of this treatment].

PMID- 15850525
TI  - [Construction and expression of RNase-resisting virus-like particles containing
      partial sequence of alpha-fetoprotein messenger RNA].

PMID- 15850526
TI  - [Effect of FZHY recipe on elastase expression in liver fibrosis in rats].

PMID- 15850527
TI  - [Inhibition of liver tumor growth by combining endostatin gene delivery with
      radiotherapy].

PMID- 15850528
TI  - [Epithelioid hemangioendothelioma of the liver: a case report].

PMID- 15850529
TI  - [Vascular endothelial growth factor and the effects of endostatin on the
      inhibition of tumor angiogenesis in treating hepatocarcinomas].

PMID- 15850530
TI  - [Assays and clinical significance for determination of hepatitis B virus
      covalently closed circular DNA].

PMID- 15850531
TI  - [The current progress of relevant proteins in lipid metabolism of hepatocytes].

PMID- 15850532
TI  - [Effect of human growth hormone treatment on the eyes of patients with
      somatotropic pituitary insufficiency and in girls with Turner's syndrome].
AB  - INTRODUCTION: The increased use of human growth hormone (hGH) in numbers of
      children rise questions concerning the safety of GH replacement therapy (GHRT).
      Adverse effects of hGH treatment (pseudotumor cerebri, papilloedema, retinal
      changes mimicking diabetic retinopathy, neovascularization) have been reported in
      some papers. PURPOSE: The aim of this study was to evaluate the influence of hGH
      therapy on the organ of vision. MATERIAL AND METHODS: 10 girls with Turner's
      syndrome aged 12-16 years (mean 13.8+/-1.69) and 20 patients with somatotropic
      pituitary insufficiency aged 7-18 years (mean 12.98+/-2.81) were studied. The
      mean duration of GHRT in patients with Turner's syndrome was 3.05+/-1.42 years
      (from 1 year to 5 year), in patients with somatotropic pituitary insufficiency
      was 2.45+/-2.32 years (from 8 months to 10 years). All patients underwent
      ophthalmic examination, including contrast sensitivity, direct and indirect
      ophthalmoscopy and fluorescein angiography. RESULTS: All parts of
      ophthalmological examination were normal. There were no abnormalities in
      fluorescein angiography. Contrast sensitivity was correct in all eyes.
      CONCLUSIONS: There was no harmful effect of GHRT on the retina and optic nerve in
      young patients. The follow-up and ophthalmologic evaluation is advisable.

PMID- 15850533
TI  - [The bone mineral density and the markers of the osseous circle in children with
      non-toxic parenchymatous or nodular goiter long-time treated with L-thyroxine].
AB  - The aim of the study was the appreciation of the influence of a therapy with L
      thyroxine on the metabolism and density of the osseous tissue (BMD) in children
      with an euthyroid diffuse and nodular goiter. The examinations included 50
      children (5 boys and 45 girls). Mean age of the investigated group: 17 years,
      time of therapy 2-5 years. The daily dose of L-thyroxine was not higher than 1-2
      microg/kg body mass. All the children were in clinical and hormonal euthyrosis.
      The control group consisted of 50 healthy children (12 boys and 38 girls), mean
      age 16,16 years. A correlation between the age of the children, TSH level and the
      markers of the osseous circle was not observed. The mean level of TSH was
      statistical significant lower in the examined group. In the examined group the
      level of PTH and ICTP in the blood serum was (PTH: 35.83+/-8.34 pg/m vs 37.21+/
      7.17 pg/ml); ICTP (8.7+/-3.87 microg/l vs 15.11+/-5.7 microg/l) was lower in the
      control group but the difference was statistical not significant (p=0.07). The
      mean concentration of PICP in the investigated group was significant lower in
      comparison with the control group. The mean level ICTP between the examined and
      control group was statistical significant (p<0.05). The mean concentration of
      osteocalcine (OC) in the treated with L-thyroxine was statistical not
      significant.

PMID- 15850534
TI  - [Cytofluorymetric evaluation of antigen regions of human thyroid peroxidase in
      patients with Graves' disease and non-toxic multinodular goiter using mouse
      monoclonal antibodies].
AB  - The aim of this study was to estimate expression of surface antigen regions of
      TPO (thyroid peroxidase: #1, #18, #30, #64 epitopes) on thyroid cells in 15
      patients with non-toxic multinodular goiter (NTMG) and 15 patients with Graves'
      disease (GD). The thyrocytes were identified by indirect method: in first stage
      we added mouse monoclonal autoantibodies specific for TPO regions and in second
      stage we conjugated this complex with rabbit anti-mouse antibodies IgG (Fab')2
      with FITC. All investigations were performed by flow cytometry using apparatus
      Coulter EPICS XL. The percentages of thyroid cells with expression of antigen
      regions of TPO 1, 18, 30, 64 were measured in relationship to the responsible
      anti-TPO concentrations: 50, 100, 200, 400, 800, 1600 microg/ml. The analysis of
      the expression of epitope #64 TPO revealed insignificantly increased percentages
      of thyroid cells in patients with GD (73% vs 45%, ns) in comparison to NTMG at
      anti-TPO antibody concentration of 1600 microg/ml. In addition, we observed that
      reduction concentration of anti-TPO antibodies leads to the decreased percentage
      of thyroid cells with antigen region #64 expression. In patients with GD
      percentage of this cells was significantly higher (48% vs 7% p<0.019, 29% vs 56%
      p<0.05) in compared to the percentage of thyroid cells from patients with NTMG at
      concentration of 200-800 microg/ml anti-TPO antibodies. Analysis of epitopes #1
      and #18 shown higher percentage of thyroid cells in GD (25% vs 20%, ns for #1
      epitope) and (25% vs 13%, ns for #18 epitope) in comparison to the patients with
      NTMG at concentration 1600 microg/ml of anti-TPO antibodies. The percentages of
      thyrocytes with epitopes #1 and #18 were decreased in relation to the reduction
      of anti-TPO concentrations. However, in all our patients epitope #30 TPO was
      found only in 8% thyroid cells. We conclude that in young patients thyroid immune
      and nonimmune diseases predispose to elevated expression of TPO epitopes (#1,
      #18, #64) which suggested increase stimulation and activation of thyroid cells
      during inflammatory reaction within thyroid gland. Furthermore, dominance
      expression of #64 TPO epitope in Graves' patients which recognized B domain could
      be a useful marker of activity of immune process in concentration between 200-800
      microg/ml of TPO antibodies.

PMID- 15850535
TI  - [Adrenal function in girls with hirsutism].
AB  - The aim of our study was to estimate the adrenal function in hirsute girls.
      MATERIAL AND METHODS: 57 girls with hirsutism aged from 12 to 19 years, mean age
      15.95 years, were involved into the study. The research was performed in early
      and middle follicular stage. Menstrual disorders were observed in 78% of them.
      Hirsutism was estimated with Ferriman-Gallwey scale (mean value 13+/-1.58), mean
      BMI was 22.7. The patients were divided into 3 groups: group 1 with clinical and
      laboratory symptoms of PCOS, n=29; group 2 with menstrual disorders and without
      elevated androgen level, n=15; group 3 without menstrual disorders and without
      elevated androgen level, n=13. RESULTS: 17OHP level was the highest in group I
      (1.17+/-0.58 ng/ml). Diurnal cortisol profile was regular in all patients. After
      Synacthen injection cortisol level rose in all groups to the similar values at 60
      min. The same stimuli induced intensive 17OHP secretion in group 1 (2.42+/-2.02
      ng/ml) at 30 min statistically higher than in group 2 (1.46+/-0.95 ng/ml),
      (p=0.045). None had 21-hydroxysase defect. There were positive correlation
      between levels of 17OHP and LH (r=0.38), 17OHP and T (r=0.39), 17OHP and LH/FSH
      (r=0.40) CONCLUSIONS: 17OHP level in patients with PCOS is significantly higher
      then in other hirsute girls. High 17OHP and normal cortisol level after Synacthen
      administration in PCOS girls point that activity of enzymes involved in 17OHP
      production is augmented.

PMID- 15850536
TI  - [Changes in blood pressure and methods of blood pressure monitoring in patients
      with type-1 diabetes].
AB  - Both diabetes mellitus and hypertension are major risk factors for
      cardiovascular, renal and atherosclerotic vascular disease. Hypertension is known
      to be more common in patients with diabetes than in the general population.
      Patients with diabetes mellitus are at high risk for renal injury, which may be
      exacerbated by abnormalities in circadian blood pressure pattern. Ambulatory
      blood pressure monitoring (ABPM) permits the observation of blood pressure
      throughout day and night in a non-medical environment, and to quantify the
      circadian blood pressure variability. Recent studies with the use of ambulatory
      blood pressure monitoring have shown that the physiological nocturnal fall in
      blood pressure is blunted or absent in some individuals with type 1 diabetes who
      are completely normotensive by conventional criteria. Patients with type 1
      diabetes and microalbuminuria have higher nocturnal blood pressure than either
      patients with type 1 diabetes and normal albumin excretion or age-matched
      controls. Moreover, changes in the circadian pattern of blood pressure in
      patients with type 1 diabetes may predict the development of albuminuria.

PMID- 15850537
TI  - [The role of ghrelin in the regulation of energy homeostasis].
AB  - Ghrelin, a novel 28 amino acid peptide, is the endogenous ligand for the growth
      hormone secretagogue receptor. The stomach is the primary source of circulating
      ghrelin, but it is also produced by the intestines, kidneys, hypothalamus,
      pituitary, placenta and pancreas. Ghrelin has been recognized as an important
      regulator of GH secretion and have important roles in energy homeostasis, glucose
      and lipid metabolism, reproduction, cardiovascular function, and immunity.
      Ghrelin has been shown to have a physiological role in the control of food
      intake, acting as an orexigenic hormone, probably by stimulating NPY production
      in contrast to the actions of leptin.

PMID- 15850538
TI  - [Anaplastic thyroid carcinoma in a 14-year-old boy].
AB  - We report a case of anaplastic cancer of thyroid in 14-year-old male. The
      diagnosis was supported on: pace of changes, clinical image, disease course, no
      effect of therapy, histopathological examination.

PMID- 15850539
TI  - [Complete androgen insensitivity syndrome in 16-year-old girl with female
      phenotype].
AB  - We present a case of a 16-year-old girl who attended Endocrinology Clinic in
      Krakow. Her main complains were amenorrhea and lack of pubic and axillary hair
      development. Breast development was normal. Based on those features, male
      karyotype (46, XY) as well as high levels of blood testosterone and lack of
      uterus on ultrasound examination allowed for establishing the diagnosis of
      complete androgen insensitivity syndrome. The authors emphasize the possibility
      of diagnosing severe disorders of sex differentiation, such as sex reversal, not
      earlier than in teenage patients with delayed puberty. In such cases the
      diagnosis can be established based on physical examination with evaluation of
      sexual development, basic blood hormonal tests and karyotype results. Reliable
      knowledge of male sex differentiation physiology is needed for their correct
      interpretation.

PMID- 15850540
TI  - [Partial gonadal dysgenesis in a 12-year-old girl--diagnostic and therapeutic
      difficulties].
AB  - The authors present a 12-year-old girl who was seen in the out-patient
      Endocrinology Clinic, University Children's Hospital of Cracow, with the
      preliminary diagnosis of androgen insensitivity syndrome, presenting with
      progressing virilisation, breast underdevelopment and dysmorphy. Pubarche was
      normal. Gynecological examination revealed ambiguous external genitalia. On
      ultrasound examination homo genic gonad-like structures without follicles were
      seen, but no uterus was present. Basic hormonal studies indicated
      hypogonadotropic hypogonadism. The child was diagnosed as partial gonadal
      dysgenesis 46, XY. A gonadectomy was performed due to the 30-40% risk of
      gonadoblastoma development characteristic for such cases, and estrogen
      substitution followed after the surgery. The authors stress the necessity of
      including partial gonadal dysgenesis and partial androgen insensitivity syndrome
      in the differential diagnosis of delayed puberty. In both the above mentioned
      syndromes the clinical features are similar but the management differs. The
      authors stress the importance of establishing the cause of the condition and
      further management prior to discharging the neonate. The ultimate sex must allow
      the patient to best fulfill his/her psychosocial role in society and reduce the
      psychological trauma.

PMID- 15850541
TI  - [Inappropriate sexual differentiation of sex reversal type in 16-year-old boy
      with male phenotype].
AB  - We present a case of a 16-year-old boy with gynecomastia and symptoms of delayed
      puberty (relatively small testes and penis), who attended the Endocrinology
      Clinic. Pubic hair development was normal. Basic hormonal blood tests showed a
      primary testicular lesion (hypergonadotropic hypogonadism). The result of
      karyotype examination showed female karyotype 46, XX. Based on those results the
      boy was diagnosed to be 46, XX male. A replacement testosterone therapy was
      administered. He stays in follow-up for gonad observation. The authors emphasize
      the possibility of establishing the diagnosis of a severe disorder belonging to
      the group of inappropriate sex differentiation of sex reversal type not earlier
      than in teenage adolescents, who present symptoms of delayed puberty. In such
      cases the main rule in establishing a final diagnosis is played by a physical
      examination with evaluation of sex development, as well as basic hormonal blood
      tests and karyotype result. Their correct interpretation is possible only by a
      physician who has reliable knowledge of the physiology of male sex determination.

PMID- 15850543
TI  - Molecular zipper assays: a simple homosandwich with the sensitivity of PCR.
AB  - PURPOSE: The purpose of this study is to develop a simple and inexpensive method
      for detection of viral load or antigens present in the body fluids as for
      diagnosis or monitoring of infectious diseases. For example, in case of viral
      infection, nucleic acid based quantitative PCR/RTPCR are sensitive in measuring
      viral load to follow the course of therapy or infection. The key limitations of
      such assays include the need for sample extraction, susceptibility to inhibitors,
      and high cost. METHODS: A molecular zipper assay based on the simple homosandwich
      concept for repeated epitopes was developed where the analyte or virus is
      sandwiched between the same antibodies for detection. A comparative study of the
      lower limit of detection of M13 model virus was performed with various
      substrates. RESULT: Homosandwich molecular zipper assay captured the model virus
      with high avidity resisting multiple rounds of washing. Detection of the virus by
      enzyme labeled MAb in combination with chemiluminescent substrates provided
      practical assay sensitivities of 7-15 phages and a theoretical detection
      sensitivity of one virus particle. CONCLUSION: The significance of our results on
      the molecular zipper assay relates to the development of ultrasensitive pathogen
      assays at low cost. Such assays could be developed for pathogenic bacteria and
      viruses, especially HIV & HCV viruses, which are ravaging impoverished continents
      of Africa, Asia and Latin America.

PMID- 15850542
TI  - Spectroscopic investigation of the aggregation state of amphotericin B during
      loading, freeze-drying, and reconstitution of polymeric micelles.
AB  - PURPOSE: To investigate the relative aggregation state of amphotericin B (AmB)
      during loading and reconstitution of polymeric micelles. METHODS: Hexanoate and
      stearate derivatives of PEO-b-p (L-Asp) were prepared. The polymers and AmB were
      dissolved in methanol (MeOH). Milli-Q water was then added slowly, and the MeOH
      was removed via rotary evaporation. The solutions were freeze-dried in the
      presence of trehalose. During micelle preparation, the aggregation state of AmB
      was assessed using absorption spectroscopy. Upon reconstitution, the samples were
      analyzed using vapor-pressure osmometry, size-exclusion chromatography (SEC), and
      absorption spectroscopy. The absorption spectrum of AmB in the presence of the
      block copolymers was compared to that of AmB alone under the same conditions.
      RESULTS: AmB was loaded into micelles prepared from acyl derivatives of PEO-b-p
      (L-Asp). Absorption spectroscopy indicated that the aggregation state was
      preserved during the loading process. AmB exists in a self-aggregated state in
      polymeric micelles containing hexanoate ester cores and in a relatively monomeric
      state in polymeric micelles containing stearate ester cores. Vapor-pressure
      osmometry confirmed the isotonicity of the formulations, while SEC indicated that
      the micelles were approximately 10(6) g/mol. CONCLUSIONS: Depending on the
      polymer structure and assembly conditions, it is possible to encapsulate AmB in a
      relatively nonaggregated or aggregated state in micelles prepared from acyl
      derivatives of PEO-b-p (L-Asp). In polymeric micelles containing stearate side
      chains, AmB was loaded in a nearly monomeric state, possibly due to interaction
      with the stearate side chains. The final aggregation state of the drug is
      preserved during lyophilization and reconstitution of polymeric micelles prepared
      by a novel solvent evaporation procedure.

PMID- 15850544
TI  - Evaluating gelatin based nanoparticles as a carrier system for double stranded
      oligonucleotides.
AB  - PURPOSE: Surface modified gelatin nanoparticles were tested as a potential
      carrier system for double stranded DNA and RNA oligonucleotides. The results will
      be discussed with regard to former experiments conducted with single stranded
      oligonucleotides. METHODS: Gelatin nanoparticles were prepared by a two step
      desolvation method and surface modified by the covalent coupling of a quaternary
      amine to obtain a permanent positive net charge. Oligonucleotide loading was
      conducted in three different media applying 50 microg oligonucleotide per mg
      nanoparticles in total. Five batches of nanoparticles varying in size and zeta
      potential (zeta) were tested. The zeta potentials were determined under enforced
      ionic conditions in a 10 mmol sodium chloride solution at pH 7.0. The separation
      of unbound oligonucleotides and gelatin nanoparticles was achieved by
      centrifugation. Free oligonucleotide was determined UV-spectrophotometrically
      (260 nm) in the supernatant. RESULTS: It could be shown that up to 50 microg
      nucleic acid per mg nanoparticles can be bound depending on the particle's zeta
      potential and the chosen incubation medium. CONCLUSIONS: The results suggest that
      the proposed procedure allows a successful drug loading of double stranded
      oligonucleotides onto to the surface of accordingly modified gelatin
      nanoparticles.

PMID- 15850545
TI  - Gelatin nanoparticles as a new and simple gene delivery system.
AB  - PURPOSE: The aim of this study was to evaluate cationized gelatin nanoparticles
      as biodegradable and low cell toxic alternative carrier to existing DNA delivery
      systems. METHODS: Native gelatin nanoparticles were produced using a two step
      desolvation method. In order to bind DNA by electrostatic interactions onto the
      surface of the particles, the quaternary amine cholamine was covalently coupled
      to the particles. The modified nanoparticles were loaded with different amounts
      of plasmid in varying buffers and compared to polyethyleneimine-DNA complexes
      (PEI polyplexes) as gold standard. Transfection ability of the loaded
      nanoparticles was tested on B16 F10 cells. Additionally, the cell toxicity of the
      formulations was monitored. RESULTS: Different setups resulted in efficient gene
      delivery displayed by exponential increase of gene expression. The gene
      expression itself occurred with a certain delay after transfection. In contrast
      to PEI polyplexes, cationized gelatin nanoparticles almost did not show any
      significant cytotoxic effects. CONCLUSIONS: Cationized gelatin nanoparticles have
      shown the potential of being a new effective carrier for nonviral gene delivery.
      The major benefit of gelatin nanoparticles is not only the very low cell
      toxicity, but also their simple production combined with low costs and multiple
      modification opportunities offered by the matrix molecule.

PMID- 15850546
TI  - Preliminary results of nanopharmaceuticals used in the radioimmunotherapy of
      ovarian cancer.
AB  - PURPOSE: The treatment of late stage ovarian cancer presents an unmet clinical
      need for women around the world. A multistep radioimmunotherapeutic (RIT)
      approach, exploiting the combination of a bispecific monoclonal antibody (BsMAb)
      with 90Y labelled biotinylated long-circulating liposomes was tested as a
      potential adjuvant treatment for epithelial ovarian carcinomatosis in an attempt
      to meet this need. This approach was used to overcome some of the major obstacles
      associated with conventional strategies, in particular, to increase the amount of
      radioactivity delivered to the tumor site compared with conventional monoclonal
      antibody (MAb) radionuclide delivery. We hypothesize that sequential
      intraperitoneal administration of the targeting and therapeutic moieties provides
      the basis for an enhanced therapeutic ratio. METHODS: A BsMAb, with anti-CA 125
      and anti-biotin epitopes was engineered for use with PEGylated liposomes coated
      with biotin to deliver the cytotoxic radionuclide 90Y to tumor sites. An in vivo
      therapy trial was used to test this RIT protocol with Balb/c nude mice (n=29)
      xenografted with the NIH:OVCAR-3 (CA 125+) human ovarian cancer cell line.
      RESULTS: A median tumor growth delay of 91 days for the combined treatment group
      versus 77.7 days for the control group was observed. CONCLUSION: An ongoing tumor
      growth delay/control study using this model has indicated an appreciable delay in
      progress of tumor and ascites development in treated vs. control populations.

PMID- 15850548
TI  - How to select and combine oral agents for patients with type 2 diabetes mellitus.
AB  - The increased number of oral agents available to treat patients with type 2
      diabetes mellitus (DM) has presented clinicians with choices about how to combine
      them when monotherapy is not adequate to achieve glycemic targets. Initial
      studies focused on whether a combination of 2 active drugs was better than a
      single active agent plus placebo. Several factors need to be considered before
      results of combination regimens from a given protocol can be compared with
      results from a different study regimen. Some of these factors include population
      characteristics, baseline control and prior therapies, length of study, and
      outcomes (glycemic and nonglycemic). Additional factors to be considered are
      costs and side effects. These studies generally demonstrate that combination
      therapy is more likely than monotherapy to achieve glucose control in patients
      not at glycemic targets. The data also demonstrate that inadequate glucose
      control with a given medication does not necessarily indicate drug failure;
      indeed, adding a new agent to an existing regimen is typically better than using
      the new agent as monotherapy. More recent studies have begun to compare regimens
      each containing 2 drugs (usually with 1 medication in common). Outcomes beyond
      glycemic control have been measured, including traditional (e.g., lipid profiles,
      albuminuria) and nontraditional (e.g., high-sensitivity C-reactive protein,
      plasminogen activator inhibitor type-1) markers. However, modifying traditional
      markers with these medications has not yet been shown to improve outcomes;
      modifying nontraditional markers is even less certain. None of these trials have
      been extended long enough to report on hard clinical end points. Nonetheless,
      certain combinations may end up being preferable because they have better impact
      on nonglycemic end points while maintaining equivalent degrees of glucose
      control. Finally, the costs of multiple medications for DM need to be weighed in
      the decision-making process faced by clinicians.

PMID- 15850549
TI  - Making the transition from oral to insulin therapy.
AB  - The typically long delay in starting insulin for patients with type 2 diabetes
      mellitus may be due in part to uncertainty about how best to make the transition
      from oral therapy to insulin. Recent studies show that when appropriate glycemic
      targets are sought, with systematic titration of insulin dosage, several methods
      of beginning insulin may be successful. Notably, either starting with a single
      injection of basal insulin or starting with 3 injections of short-acting insulin
      at mealtimes can be effective. Studies also suggest that continuing oral
      therapies and using insulin analogues rather than human insulins may improve the
      effectiveness of insulin treatment relative to the rate of hypoglycemia and gain
      of weight typically seen in this setting. Starting with a single injection of
      insulin to control basal glycemia while continuing oral therapy is the simplest
      approach, and lends itself to stepwise addition of mealtime injections as needed
      to bring most patients to glycemic targets in a logical and practical way. Future
      studies should consider not only the ability of regimens to reach hemoglobin
      A(1c) targets but also the burden of adverse effects accompanying this effort
      with a given method.

PMID- 15850550
TI  - Intensifying insulin therapy in patients with type 2 diabetes mellitus.
AB  - The current paradigm for pharmacologic management of type 2 diabetes mellitus
      (DM) is to progress with oral agents until severe insulin deficiency develops, at
      which time insulin can be initiated. Reexamination of data from the Diabetes
      Control and Complications Trial (DCCT) suggests that glycemic variability may be
      an important factor involved in the pathogenesis of microvascular complications.
      It is now appreciated that oxidative stress from overproduction of reactive
      oxygen species may be the result of this glycemic variability, suggesting that an
      overemphasis of basal insulin may not be the ideal strategy for insulin
      replacement, even though basal insulin is often the only insulin used initially.
      Although finding the best insulin program for treatment of type 2 DM is an
      important area of research, almost all patients with severe insulin deficiency
      will require both basal and prandial replacement. Use of adequate lag times (time
      between injecting the prandial insulin and eating), U-500 insulin (500 U/mL human
      regular insulin), and home blood glucose monitoring to determine "glycemic trend"
      are important tools that are readily available to all patients.

PMID- 15850551
TI  - Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus.
AB  - Many patients who have type 2 diabetes mellitus (DM) require several different
      medications. Although these agents can substantially reduce diabetes-related
      morbidity and mortality, the extent of treatment benefits may be limited by a
      lack of treatment adherence. Unfortunately, little information is available on
      treatment adherence in patients with type 2 DM. Available data indicate
      substantial opportunity for improving clinical outcomes through improved
      treatment adherence. Factors that appear to influence adherence include the
      patient's comprehension of the treatment regimen and its benefits, adverse
      effects, medication costs, and regimen complexity, as well as the patient's
      emotional well-being. Outcomes research emphasizes the importance of effective
      patient-provider communication in overcoming some of the barriers to adherence.
      This article offers specific suggestions for improving adherence in patients with
      type 2 DM seen in general clinical practice.

PMID- 15850552
TI  - Supraphysiological concentrations of 5-aminolevulinic acid dimerize in solution
      to produce superoxide radical anions via a protonated dihydropyrazine
      intermediate.
AB  - 5-aminolevulinic acid (ALA) is the committed biological precursor to porphyrins.
      At supraphysiological concentrations ALA can dimerize to form 3,6-dihydropyrazine
      2,5-dipropanoic acid (DHPY), which transfers electrons to XTT in a reaction that
      does not require metal ions and is specifically inhibited by superoxide
      dismutase. The formation of DHPY from ALA follows dimerization kinetics with a pK
      of 7.8+/-0.1. At pH 11.2, DHPY is relatively stable, but when the pH is dropped
      to 6.0 rapid conversion to 2,5-(beta-carboxyethyl)pyrazine occurs via an
      intermediate with an absorption maximum of 370 nm. Formation of this intermediate
      is pH-dependent with a pK of 6.0+/-0.1. These data indicate that ALA dimerizes to
      produce superoxide from a protonated form of DHPY. The significance of these
      results with respect to the concentrations of ALA used in photodynamic therapy,
      and the increased incidence of liver cancer in acute intermittent porphyria, is
      discussed.

PMID- 15850553
TI  - Inhibition of very long chain acyl-CoA dehydrogenase during cardiac ischemia.
AB  - The heart utilizes primarily fatty acids for energy production. During ischemia,
      however, diminished oxygen supply necessitates a switch from beta-oxidation of
      fatty acids to glucose utilization and glycolysis. Molecular mechanisms
      responsible for these alterations in metabolism are not fully understood.
      Mitochondrial acyl-CoA dehydrogenase catalyzes the first committed step in the
      beta-oxidation of fatty acids. In the current study, an in vivo rat model of
      myocardial ischemia was utilized to determine whether specific acyl-CoA
      dehydrogenases exhibit ischemia-induced alterations in activity, identify
      mechanisms responsible for changes in enzyme function, and assess the effects on
      mitochondrial respiration. Very long chain acyl-CoA dehydrogenase (VLCAD)
      activity declined 34% during 30 min of ischemia. Loss in activity appeared
      specific to VLCAD as medium chain acyl-CoA dehydrogenase activity remained
      constant. Loss in VLCAD activity during ischemia was not due to loss in protein
      content. In addition, activity was restored in the presence of the detergent
      Triton X-100, suggesting that changes in the interaction between the protein and
      inner mitochondrial membrane are responsible for ischemia-induced loss in
      activity. Palmitoyl-carnitine supported ADP-dependent state 3 respiration
      declined as a result of ischemia. When octanoyl-carnitine was utilized state 3
      respiration remained unchanged. State 4 respiration increased during ischemia, an
      increase that appears specific to fatty acid utilization. Thus, VLCAD represents
      a likely site for the modulation of substrate utilization during myocardial
      ischemia. However, the dramatic increase in mitochondrial state 4 respiration
      would be predicted to accentuate the imbalance between energy production and
      utilization.

PMID- 15850554
TI  - FAD semiquinone stability regulates single- and two-electron reduction of
      quinones by Anabaena PCC7119 ferredoxin:NADP+ reductase and its Glu301Ala mutant.
AB  - Flavoenzymes may reduce quinones in a single-electron, mixed single- and two
      electron, and two-electron way. The mechanisms of two-electron reduction of
      quinones are insufficiently understood. To get an insight into the role of flavin
      semiquinone stability in the regulation of single- vs. two-electron reduction of
      quinones, we studied the reactions of wild type Anabaena
      ferredoxin:NADP(+)reductase (FNR) with 48% FAD semiquinone (FADH*) stabilized at
      the equilibrium (pH 7.0), and its Glu301Ala mutant (8% FADH* at the equilibrium).
      We found that Glu301Ala substitution does not change the quinone substrate
      specificity of FNR. However, it confers the mixed single- and two-electron
      mechanism of quinone reduction (50% single-electron flux), whereas the wild type
      FNR reduces quinones in a single-electron way. During the oxidation of fully
      reduced wild type FNR by tetramethyl-1,4-benzoquinone, the first electron
      transfer (formation of FADH*) is about 40 times faster than the second one
      (oxidation of FADH*). In contrast, the first and second electron transfer
      proceeded at similar rates in Glu301Ala FNR. Thus, the change in the quinone
      reduction mechanism may be explained by the relative increase in the rate of
      second electron transfer. This enabled us to propose the unified scheme of single
      , two- and mixed single- and two-electron reduction of quinones by flavoenzymes
      with the central role of the stability of flavin/quinone ion-radical pair.

PMID- 15850555
TI  - Apoptosis and cell recovery in response to oxidative stress in p53-deficient
      prostate carcinoma cells.
AB  - We have studied the effects of different concentrations of H(2)O(2) on the
      proliferation of PC-3 prostate carcinoma cells. Since this cell line lacks
      functional p53, we sought to characterize whether apoptotic response to the
      oxidative insult was altered such that, unlike in cells containing functional p53
      apoptosis may be reduced and replaced by other mechanisms of cellular arrest and
      death. We did not observe necrosis in PC-3 cells treated with H(2)O(2)
      concentrations of up to 500 microM. In the presence of 50 microM H(2)O(2), arrest
      was observed in the G2-phase of the cell cycle, along with p53-independent
      apoptosis. In the presence of 500 microM H(2)O(2), addition of l-buthionine
      sulfoximine increased the percentage of apoptotic cell death. Senescence
      associated cell arrest was never observed. Moreover, some of the treated cells
      seemed to be resistant to oxidative damage. These cells re-entered the cell cycle
      and proliferated normally. Analysis of the expression of p21(waf1) and of p21
      protein levels, as well as the activity of caspase-3 and caspase-8, allowed us to
      characterize some aspects of the arrest of PC-3 cells in G2 and the apoptotic
      response to oxidative stress in the absence of functional p53.

PMID- 15850556
TI  - Purification and characterization of a novel ATP-independent type I DNA
      topoisomerase from a marine methylotroph.
AB  - DNA topoisomerase is involved in DNA repair and replication. In this study, a
      novel ATP-independent 30-kDa type I DNA topoisomerase was purified and
      characterized from a marine methylotroph, Methylophaga sp. strain 3. The purified
      enzyme composed of a single polypeptide was active over a broad range of
      temperature and pH. The enzyme was able to relax only negatively supercoiled DNA.
      Mg(2+) was required for its relaxation activity, while ATP gave no effect. The
      enzyme was clearly inhibited by camptothecin, ethidium bromide, and single
      stranded DNA, but not by nalidixic acid and etoposide. Interestingly, the
      purified enzyme showed Mn(2+)-activated endonuclease activity on supercoiled DNA.
      The N-terminal sequence of the purified enzyme showed no homology with those of
      other type I enzymes. These results suggest that the purified enzyme is an ATP
      independent type I DNA topoisomerase that has, for the first time, been
      characterized from a marine methylotroph.

PMID- 15850557
TI  - Comparative studies of the artificial chaperone-assisted refolding of thermally
      denatured bovine carbonic anhydrase using different capturing ionic detergents
      and beta-cyclodextrin.
AB  - Artificial chaperone-assisted refolding has been shown to be an effective
      approach for improving the refolding yield of some of the denatured proteins.
      Since identical concentrations of various detergents do not induce similar
      variations in the protein structures, we arranged to evaluate the artificial
      chaperoning capabilities of several ionic detergents as a function of charge,
      structure, and the hydrophobic tail length of the detergent. Our results indicate
      that carbonic anhydrase can be refolded from its denatured state via artificial
      chaperone strategy using both anionic and cationic detergents. However, the
      extent of refolding assistance (kinetic and refolding yield) were different due
      to protein and detergent net charges, detergent concentrations, and the length of
      hydrophobic portion of each detergent. These observed differences were attributed
      to physical properties of CA-detergent complexes and/or to the kinetics of
      detergent stripping by beta-cyclodextrin from the protein-detergent complexes
      which is apparently dependent on the detergent-beta-CD association constants and
      the nature of the partially stripped complexes.

PMID- 15850558
TI  - The puhE gene of Rhodobacter capsulatus is needed for optimal transition from
      aerobic to photosynthetic growth and encodes a putative negative modulator of
      bacteriochlorophyll production.
AB  - A conserved orf of previously unknown function (herein designated as puhE) is
      located 3' of the reaction centre H (puhA) gene in purple photosynthetic
      bacteria, in the order puhABCE in Rhodobacter capsulatus. Disruptions of R.
      capsulatus puhE resulted in a long lag in the growth of photosynthetic cultures
      inoculated with cells grown under high aeration, and increased the level of the
      peripheral antenna, light-harvesting complex 2 (LH2). The amount of the
      photosynthetic reaction centre (RC) and its core antenna, light-harvesting
      complex 1 (LH1), was reduced; however, there was no decrease in expression of a
      lacZ reporter fused to the puf (RC and LH1) promoter, in RC assembly in the
      absence of LH1, or in LH1 assembly in the absence of the RC. In strains that lack
      LH2, disruption of puhE increased the in vivo absorption at 780 nm, which we
      attribute to excess bacteriochlorophyll a (BChl) pigment production. This effect
      was seen in the presence and absence of PufQ, a protein that stimulates BChl
      biosynthesis. Expression of puhE from a plasmid reduced A(780) production in puhE
      mutants. We suggest that PuhE modulates BChl biosynthesis independently of PufQ,
      and that the presence of excess BChl in PuhE(-)LH2(+) strains results in excess
      LH2 assembly and also interferes with the adaptation of cells during the
      transition from aerobic respiratory to anaerobic photosynthetic growth.

PMID- 15850559
TI  - c-Abl tyrosine kinase regulates c-fos gene expression via phosphorylating RNA
      polymerase II.
AB  - c-Abl tyrosine kinase, predominantly distributed in nucleus, has been implicated
      in many important cellular processes including the regulation of gene
      transcription. In this study, we showed that c-Abl promoted the transcription of
      c-fos gene, both exogenously and endogenously. The nuclear localization and
      tyrosine kinase activity of c-Abl were required for the activation of c-fos gene.
      c-Abl was associated with RNA polymerase II (RNAP II) in vivo and augmented the
      tyrosine phosphorylation of the largest subunit of RNAP II. In addition, c-Abl
      and RNAP II could be recruited to the region of c-fos promoter. The combined
      results suggest that c-Abl plays an important role in the transcriptional
      regulation of c-fos gene and the tyrosine phosphorylation of the largest subunit
      of RNAP II by c-Abl is involved in the regulating process.

PMID- 15850560
TI  - Analysis of the stability and function of nucleoplasmin through cysteine mutants.
AB  - Xenopus laevis nucleoplasmin is a pentameric nuclear chaperone. The relation
      between the structure and the multifunctional aspects of the molecule has not yet
      been clearly established. In the course of analysing a C-terminally His-tagged
      recombinant version of the region equivalent to the trypsin resistant core (r
      NP142) of the molecule, we found that this domain exhibited a substantially
      decreased oligomerization potential. To better understand the role of the three
      cysteines of nucleoplasmin on its pentameric functional structure, we have
      selectively mutated these residues to serine and generated three mutants (C15S,
      C35S, and C45S) both for the complete recombinant nucleoplasmin (r-NP) and the
      truncated r-NP142 non-tagged forms. We demonstrate that there are no disulphide
      bridges stabilizing either the monomer or the pentamer. Neither C15S nor C35S has
      any structural effects, while the mutation C45S abolishes the ability of r-NP142
      to pentamerize. This structural impairment suggests that hydrophobic interactions
      of Cys 45 are critical for the stability of the protein. Our studies allow to
      analyse for the first time the structural and functional properties of
      nucleoplasmin in its monomeric form.

PMID- 15850561
TI  - Relaxation kinetics of the interaction between RNA and metal-intercalators: the
      Poly(A).Poly(U)/platinum-proflavine system.
AB  - The interactions of Poly(A).Poly(U) with the cis-platinum derivative of
      proflavine [{PtCl(tmen)}(2){HNC(13)H(7)(NHCH(2)CH(2))(2)}](+) (PRPt) and
      proflavine (PR) are investigated by spectrophotometry, spectrofluorimetry and T
      jump relaxation at I=0.2M, pH 7.0, and T=25 degrees C. Base-dye interactions
      prevail at high RNA/dye ratio and binding isotherms analysis reveals that both
      dyes bind to Poly(A).Poly(U) according to the excluded site model (n=2). Only one
      relaxation effect is observed for the Poly(A).Poly(U)/PRPt system, whereas two
      effects are observed with Poly(A).Poly(U)/PR. The results agree with the sequence
      D+S <==> D, S <==> DS(I) <==> DS(II), where D,S is an external complex, DS(I) is
      a partially intercalated species, and DS(II) is the fully intercalated complex.
      Formation of DS(II) could be observed in the case of proflavine only. This result
      is interpreted by assuming that the platinum-containing residue of PRPt hinders
      the full intercalation of the acridine residue.

PMID- 15850562
TI  - Chloroperoxidase-catalyzed oxidation of 4,6-dimethyldibenzothiophene as dimer
      complexes: evidence for kinetic cooperativity.
AB  - A sigmoidal kinetic behavior of chloroperoxidase for the oxidation of 4,6
      dimethyldibenzothiophene (4,6-DMDBT) in water-miscible organic solvent is for the
      first time reported. Kinetics of 4,6-DMDBT oxidation showed a cooperative profile
      probably due to the capacity of chloroperoxidase to recognize a substrate dimer
      (pi-pi dimer) in its active site. Experimental evidence is given for dimer
      formation and its presence in the active site of chloroperoxidase. The kinetic
      data were adjusted for a binding site able to interact with either monomer or
      dimer substrates, producing a cooperative model describing a one-site binding of
      two related species. Determination of kinetics constants by iterative
      calculations of possible oxidation paths of 4,6-DMDBT suggests that kinetics
      oxidation of dimer substrate is preferred when compared to monomer oxidation.
      Steady-state fluorometry of substrate in the absence and presence of
      chloroperoxidase, described by the spectral center of mass, supports this last
      conclusion.

PMID- 15850563
TI  - Essential regions for antiviral activities of actinohivin, a sugar-binding anti
      human immunodeficiency virus protein from an actinomycete.
AB  - Actinohivin (AH) is a potent anti-human immunodeficiency virus (HIV) protein that
      consists of highly conserved three-tandem repeats (segments 1, 2, and 3). The
      molecular target of AH in its anti-HIV activity is high-mannose-type saccharide
      chains of HIV gp120. This article deals with sequence requirements for the anti
      HIV activity of AH. The deleted or substituted DNAs encoding AH or His-AH were
      prepared using mutagenic oligonucleotide primers in PCR. The mutant constructs
      were expressed in Escherichia coli, and the activities of the recombinant protein
      products were examined by a syncytium-formation assay system that mimics anti-HIV
      activity. The single segment mutant His-AHs showed no anti-syncytium-formation
      activity, but the mutant His-AHs, which consists of 2 or 3 segments, retained
      reduced activities. His-AH(6-114) dramatically reduced the anti-syncytium
      formation activity to that of His-AH(36-114) or His-AH(I5A). Furthermore, His
      AH(Q33A), His-AH(Q71A), and His-AH(Q109A) in which glutamine residues were
      substituted into alanine showed reduced activities of 1/20, 1/10, and 1/30,
      respectively, in anti-syncytium formation compared with His-AH. These results
      indicate that three segments of AH are necessary for potent anti-syncytium
      formation activity-that is, for potent anti-HIV activity and the cooperated
      involvement of each segment of AH increased the AH-gp120 interaction.

PMID- 15850564
TI  - DNA immunizations with M2 muscarinic and beta1 adrenergic receptor coding
      plasmids impair cardiac function in mice.
AB  - Autoimmune mediated myocardial damage is likely to be a pathogenic mechanism for
      acquired dilated cardiomyopathies. Evidence confirms that autoantibodies that
      bind to M(2) muscarinic (M(2)AChR) and beta(1) adrenergic receptors (beta(1)AR)
      are present in idiopathic dilated cardiomyopathy and Chagasic patients' sera. To
      elucidate the role of these antibodies in cardiac functional impairment, we used
      a murine model immunized with plasmids encoding the M(2)AChR or beta(1)AR via
      gene-gun bombardment. Anti-M(2)AChR and beta(1)AR antibodies were detected over
      the course of 37 weeks. These antibodies were directed to the second
      extracellular loop (el2) of both receptors and the third intracellular loop (il3)
      of the M(2)AChR. Peak antibody titers from weeks 2 to 5 against M(2)AChR-el2 and
      beta(1)AR-el2 as well as elevated titers against M(2)AChR-il3 were detected. Anti
      M(2)AChR-il3 and anti-beta(1)AR-el2 antibodies were predominant in IgG1 subclass
      immunoglobulins, suggesting a T-helper-2 biased lymphocyte response. Heart
      morphology and function was assessed by echocardiography over the course of 42
      weeks. Data showed progressive decrease in left ventricular (LV) wall thickness
      and LV mass that was mostly evident for beta(1)AR-immunized mice albeit a small
      change in LV dimensions. Fractional shortening was altered and values of 41%, 37%
      and 48% were observed at week 42 for the M(2)AChR, beta(1)AR and control groups
      respectively. In support of autonomic deregulation, a twofold increase in
      M(2)AChR and a similar decrease in beta(1)AR density were observed in radioligand
      saturation assays for both experimental groups. Histological analysis revealed
      myofibril disarray and fibrosis, pointing towards remodeling as a consequence of
      the long-term presence of anti-receptor antibodies.

PMID- 15850565
TI  - Enhancement of PAI-1 mRNA in cardiovascular cells after kainate injection is
      mediated through the sympathetic nervous system.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is a major physiological regulator of
      the fibrinolytic system and is thought to promote vascular diseases. Recently, we
      have reported that PAI-1 gene expression was markedly enhanced locally in
      cardiovascular cells immediately after injecting (i.p.) mice with kainate, an
      analog of glutamate, which is the principal excitatory neurotransmitter in the
      central nervous system. Here we investigated whether the induction of PAI-1 mRNA
      by kainate could be mediated through sympathetic versus parasympathetic efferent
      neurons. To this end, we used a group of drugs known to interfere with the
      aforementioned pathways. PAI-1 gene expression was monitored in the heart via in
      situ hybridization using (35)S-labeled PAI-1-specific riboprobes. We have found
      that the elevation of PAI-1 mRNA levels, as detected 3 h after systemic
      administration of kainate, was reduced by mecamylamine, guanethidine and
      phentolamine, but not by propranolol or atropine. In addition, the adrenergic
      agonists phenylephrine and adrenaline themselves, but not clonidine, induced PAI
      1 with a spatial distribution similar to that of kainate (i.e. in coronary
      arteries throughout the heart, and in cardiocytes in the left ventricular and
      atrial myocardium). Collectively, these results show that kainate activated the
      PAI-1 gene in cardiovascular cells primarily through the sympathetic nervous
      system (SNS), via the alpha1-adrenergic receptor. Hence, the results suggest that
      PAI-1 is likely to be increased during enhanced sympathetic efferent neuronal
      activity, such as occurring in heart failure or cardiac hypertrophy. The results
      also reinforce the previously reported linkage of PAI-1 to physiological stress.
      Furthermore, to our knowledge, this is the first demonstration that glutamate can
      enhance gene expression in a peripheral tissue. Thus, these findings raise the
      possibility that glutamate, acting via the SNS, can affect cardiovascular
      homeostasis and pathology by modulating gene expression in cardiac myocytes and
      vascular cells.

PMID- 15850566
TI  - Ischemia depletes dystrophin and inhibits protein synthesis in the canine heart:
      mechanisms of myocardial ischemic injury.
AB  - In this study we tested our previous hypothesis that ischemia is a multifactorial
      injurious event involving all components of the myocyte simultaneously. This
      hypothesis was based on ultrastructural findings and was now tested again by
      protein analysis of sarcolemmal structural proteins and of markers of
      transcriptional and translational activities. This knowledge may help to clarify
      the cellular mechanisms involved in progression of acute ischemic myocardial
      injury and reperfusion. Therefore, we investigated all three
      intracellular/extracellular linkage systems of the sarcolemma using antibodies
      against dystrophin, beta-dystroglycan, gamma-sarcoglycan, vinculin, beta1
      integrin, laminin, and spectrin. In addition, antibodies were used to evaluate
      membrane permeability (albumin), transcriptional efficacy (non-snRNP splicing
      factor SC-35), and translational capacity (phosphorylated p70 ribosomal protein
      S6 kinase). Tissue samples were obtained from a canine model of regional
      myocardial ischemia (90 min or 4.5 h) with or without reperfusion. Immunoconfocal
      microscopy and Western blotting revealed that the rank order of sensitivity was
      the following: dystrophin, beta-dystroglycan, gamma-sarcoglycan, vinculin,
      spectrin, integrin and laminin. Different levels of dystrophin loss indicate
      reversible/irreversible injury as established by albumin uptake and electron
      microscopy. Dystrophin depletion closely coincided with generally depressed
      transcription and translation. These changes occurred simultaneously in a time
      dependent manner and persisted during reperfusion. In conclusion, damage of the
      different structural proteins results in membrane destabilization and disruption
      of the contractile apparatus from the sarcolemma. These changes, concomitantly
      associated with disturbances in transcription and translation, are major
      mechanisms determining the transition to irreversibility of myocardial ischemic
      injury and confirm our hypothesis that ischemia is a multifactorial injurious
      event involving all components of the cardiac myocyte.

PMID- 15850567
TI  - The role of p38 in the regulation of Na+-Ca2+ exchanger expression in adult
      cardiomyocytes.
AB  - The Na(+)-Ca(2+) exchanger is crucial in the regulation of [Ca(2+)](i) in the
      cardiac myocyte. The exchanger is upregulated in cardiac hypertrophy and failure.
      This upregulation can have an effect on calcium transients and possibly
      contribute to diastolic dysfunction and an increased risk of arrhythmias. Here we
      use adenovirus mediated gene expression to examine the role of p38 MAP kinase in
      upregulation of the exchanger in adult cardiac myocytes. We demonstrate that p38
      mediates a part of the alpha-adrenergic stimulated upregulation of the Na(+)
      Ca(2+) exchanger gene. Overexpression of dominant-negative p38 isoforms and
      activated MKK3 and MKK6 in isolated adult cardiac myocytes demonstrates that p38
      activation is sufficient for NCX1 promoter upregulation and that this is mediated
      primarily by the p38alpha isoform. Lastly, this work demonstrates that the
      p38alpha stimulated upregulation of the NCX1 promoter is mediated via the -80
      CArG box element. This is the first time that a specific role for p38alpha in
      gene regulation has been demonstrated in isolated adult cardiomyocytes and
      provides an important clue to our understanding some of the factors regulating
      exchanger gene expression in the hypertrophic and failing heart.

PMID- 15850568
TI  - Long-term cardiac gene expression using a coxsackieviral vector.
AB  - Efficient myocardial gene transfer in the intact adult heart is difficult using
      conventional transfer vectors. Since coxsackievirus B3 (CVB3) is cardiotropic, it
      may be possible to exploit its cardiotropic characteristics to design a vector
      for gene transfer to the intact heart. We generated a recombinant CVB3 cDNA by
      inserting a green fluorescent protein (GFP) gene immediately upstream from the
      VP0 capsid protein of CVB3. The infectious virus (rCVB3-GFP) was recovered from
      the supernatants of the transfected Cos-7 cells, and was grown in HeLa cells to
      titers of 10(11) pfu/ml. In the rCVB3-GFP infected HeLa cells and neonatal rat
      cardiac myocytes, GFP protein expression was documented by immunoblot and by
      fluorescent microscopy. GFP expression was maintained after five passages in HeLa
      cells. To test in vivo expression of GFP, we infected 8-week-old inbred female
      Balb/C mice with 10(6) pfu of rCVB3-GFP, intraperitoneally. GFP was present in up
      to 30% of cardiac myocytes over the 8 weeks post infection (p.i.) and it was co
      localized with CVB3 infection. Surprisingly, in spite of detection of GFP up to
      at least 8 weeks after infection, there was no mortality in the mice. It is
      possible to express exogenous proteins in the intact heart after an
      intraperitoneal (i.p.) injection of recombinant coxsackievirus. The duration of
      expression persisted for at least 8 weeks with little immune response nor
      mortality. These results demonstrated that the cardiac tropism of CVB3 could be
      used to design vectors for efficient gene expression in the intact heart.

PMID- 15850569
TI  - Protein kinase C delta and epsilon mediate positive inotropy in adult ventricular
      myocytes.
AB  - To examine cardiac contractile regulation and protein kinase C (PKC)
      translocation in parallel, the delta and epsilon isoforms of PKC were fused to
      green fluorescent protein (GFP) and expressed in adult rat ventricular myocytes
      maintained in short term culture. PKC-delta-GFP and PKC-epsilon-GFP were
      predominantly cytosolic until phorbol dibutyrate (PDBu) was introduced. PKC-delta
      GFP redistributed preferentially to perinuclear structures that co-localized with
      a Golgi marker, whereas PKC-epsilon-GFP redistributed preferentially to the
      surface sarcolemma. Myocyte contractile function was assessed by monitoring
      twitch shortening with field stimulation at 0.5 Hz, 22 degrees C. In myocytes
      expressing PKC-delta-GFP, PDBu caused a transient negative inotropic response
      followed by a robust and sustained positive inotropic response that paralleled
      perinuclear PKC-delta accumulation. In PKC-epsilon-GFP myocytes, PDBu caused a
      sustained negative inotropic response that paralleled accumulation at the surface
      sarcolemma, but this response did not differ from myocytes expressing GFP alone.
      At higher expression levels, PKC-epsilon-GFP myocytes responded more like PKC
      delta-GFP myocytes including perinuclear accumulation and a sustained positive
      inotropic response. Positive inotropic responses were markedly attenuated if PKC
      translocation was biased toward the surface sarcolemma by use of a more
      hydrophobic PKC activator, and were completely and selectively blocked by the PKC
      antagonist bis-indoylmaleimide. In contrast, transient and sustained negative
      inotropic responses were selectively blocked by the Ca(2+)-dependent PKC isoform
      antagonist Go6976. The data indicate that the novel PKC isoforms delta and
      epsilon have little effect on contractility when accumulating at the cell
      surface, but produce a strong positive inotropic response upon accumulation at
      the Golgi or other intracellular sites.

PMID- 15850571
TI  - A comparative serial echocardiographic analysis of cardiac structure and function
      in rats subjected to pressure or volume overload.
AB  - Heart failure is a leading cause of death that is reaching epidemic proportions.
      It is a clinical syndrome attributable to a multitude of factors that begins with
      a compensatory response known as hypertrophy, followed by a decompensatory
      response that eventually results in failure. Heart failure can be triggered when
      the heart is subjected to extended periods of pathological pressure overload (PO)
      or volume overload (VO). To date there have been no comparative serial
      echocardiographic studies outlining the progression of hypertrophy in PO versus
      VO rats. We hypothesized that PO or VO would induce differential cardiac
      remodeling leading to contractile dysfunction with subsequent heart failure. To
      address this hypothesis we used echocardiography to study the serial progression
      of heart structure and function in rat models of both PO- and VO-induced
      hypertrophy. PO or VO were induced by performing abdominal aortic banding or
      aortocaval shunt procedures, respectively, while cardiac structure and function
      were assessed in both models by M-mode and Doppler echocardiography at key time
      intervals. PO rats showed progressive wall thickening consistent with concentric
      hypertrophy, while VO rats showed marked left ventricular dilatation consistent
      with eccentric hypertrophy. Systolic dysfunction occurred early in VO compared to
      PO. Diastolic dysfunction was evident in PO, while VO showed signs of enhanced
      diastolic function. PO and VO induced differential changes in cardiac structure
      and function during the progression of compensated hypertrophy to decompensated
      heart failure.

PMID- 15850570
TI  - Peroxynitrite activates ERK via Raf-1 and MEK, independently from EGF receptor
      and p21Ras in H9C2 cardiomyocytes.
AB  - Peroxynitrite is a potent oxidant and nitrating species proposed as a direct
      effector of myocardial damage in a wide range of cardiac diseases. Whether
      peroxynitrite also acts indirectly, by modulating cell signal transduction
      pathways in the myocardium, has not been investigated. Here, we examined the
      ability of peroxynitrite to activate extracellular signal-related kinase (ERK), a
      MAP kinase which has been linked with hypertrophic and anti-apoptotic responses
      in the heart, in cultured H9C2 cardiomyocytes. Peroxynitrite elicited a
      concentration- and time-dependent activation of ERK, secondary to the upstream
      activation of MEK 1 (ERK kinase). Activation of MEK-ERK by peroxynitrite was
      related to the upstream activation of Raf-1 kinase, as ERK and MEK
      phosphorylation were prevented by the Raf-1 inhibitor BAY43-9006. These effects
      of peroxynitrite were not associated with the activation of p21(Ras), known as a
      common signaling target of cellular oxidative stress. In contrast to ERK
      activation mediated by the epidermal growth factor (EGF), ERK activation by
      peroxynitrite was not prevented by AG1478 (EGF receptor inhibitor). Peroxynitrite
      acted through oxidative, but not nitrative chemistry, as ERK remained activated
      while nitration was prevented by the flavanol epicatechin. In addition to ERK,
      peroxynitrite also potently activated two additional members of the MAP kinase
      family of signaling proteins, JNK and p38. Thus, peroxynitrite activates ERK in
      cardiomyocytes through an unusual signaling cascade involving Raf-1 and MEK 1,
      independently from EGFR and P21(Ras), and also acts as a potent activator of JNK
      and p38. These results provide the novel concept that peroxynitrite may represent
      a previously unrecognized signaling molecule in various cardiac pathologies.

PMID- 15850572
TI  - Dysregulation of connexins and inactivation of NFATc1 in the cardiovascular
      system of Nkx2-5 null mutants.
AB  - In humans, mutations of the gene encoding the transcription factor Nkx2-5 result
      in the heart in electrical conduction defects and morphological abnormalities. In
      this organ Nkx2-5 is expressed in both the myocardium and the endocardium.
      Connexins (Cxs) are gap junction channel proteins that have been shown to be
      involved in both heart development and cardiac electrical conduction, suggesting
      a possible correlation between expression of Cxs and Nkx2-5. To evaluate this
      correlation, the expression of Cxs has been investigated in the cardiovascular
      system of wild-type and Nkx2-5-/- 9.2 days post-conception (dpc) mouse embryos.
      The disruption of the Nkx2-5 gene results in the loss of Cx43 in the heart, due
      in part to the poor development of the ventricular trabecular network, as well as
      specific downregulation of Cx45 gene expression. In addition, the nuclear
      translocation of NFATc1 in the endocardial endothelial cells is inhibited in the
      Nkx2-5-/- embryos. These results indicate for the first time that Nkx2-5 is
      involved in the transcriptional regulation of the Cx45 gene expression. In the
      mutant embryos the aorta is collapsed, and the vascular endothelial Cxs, Cx40 and
      Cx37, are no longer expressed in its posterior region. Poor development of the
      trabeculae and downregulation of Cx45 may contribute both to failure of the
      myocardial function and to hemodynamic insufficiency. The latter, in turn, may
      result in the dysregulation of Cx40 and -37 expressions along the whole length of
      the aorta. Direct or indirect effects of Nkx2-5 inactivation on the Cx45 gene
      expression could explain the absence of the endocardial cushions in the heart of
      Nkx2-5-/- embryos.

PMID- 15850573
TI  - Use of recombinant adeno-associated viral vectors as a tool for labeling bone
      marrow cells.
AB  - We have tested the feasibility of using recombinant adeno-associated virus (rAAV)
      vectors as a tool for labeling bone marrow (BM) cells in vivo. We infected BM
      cells of donor FVB mice with rAAV vectors containing the lacZ gene for 2 h. We
      then injected the rAAV-infected cells to lethally irradiated-recipient FVB mice.
      Peripheral blood (PB), BM and spleen harvested at 4 weeks after BM transplant
      (BMT) demonstrated stable engraftment in beta-galactosidase (beta-gal)
      expression. In contrast, Dil-labeling displayed only a faint signal 4 weeks after
      BMT. To analyze the kinetics of BM cells, we injected vascular endothelial growth
      factor (VEGF), which promotes mobilization of BM cells. Administration of VEGF
      protein significantly increased the rAAV-mediated beta-gal expression in PB and
      BM of recipient mice. Moreover, when myocardial infarction was induced in BMT
      mice, the ischemic area exhibited significant beta-gal staining in rAAV-labeled
      BMT group. rAAV vectors programmed stable transduction in BM cells in vivo
      through rapid infection. rAAV appears to represent a useful vector for labeling
      BM cells ex vivo prior to BMT for analysis of cardiovascular therapeutic
      purposes.

PMID- 15850574
TI  - Skeletal muscle myofibrillar protein oxidation in heart failure and the
      protective effect of Carvedilol.
AB  - Heart failure is characterized by limited exercise tolerance and by a skeletal
      muscle myopathy with atrophy and shift toward fast fibres. An inflammatory status
      with elevated pro-inflammatory cytokines and exaggerated free radicals
      production, can worsen muscle damage. In a well established model of heart
      failure, the monocrotaline treated rat, we show that CHF is accompanied by
      oxidation of the skeletal muscle actin, tropomyosin and myosin, which further
      depresses muscle function and exercise capacity. We have also tested the efficacy
      of Carvedilol, a non-selective beta(1)-beta(2)-blocker, which has been widely
      used in clinical trials to improve exercise tolerance and reduce mortality in
      moderate and severe CHF, in preventing contractile protein oxidation in CHF rats.
      As comparison we used Bisoprolol a beta(1) selective agent, without known anti
      oxidative properties. Carvedilol at the dose of 2 mg/kg per day was able to
      prevent the myofibrillar protein oxidation, while Bisoprolol (0.1 mg/kg) did it
      only partially, as demonstrated by the oxyblot analysis. While Carvedilol
      improved force production on isolated muscles, Bisoprolol did not. After the
      COMET trial, the anti-oxidative capacity of Carvedilol has been invoked as one of
      the mechanism that makes this drug superior to other selective beta-blockers in
      the treatment of CHF. One of the reason of Carvedilol superiority could be the
      effect on skeletal muscle with reduction of contractile protein peroxidation,
      amelioration of muscle function and improvement of exercise tolerance. Inhibition
      of reactive oxygen species (ROS) production, and of pro-inflammatory cytokines
      may also lead to a decreased muscle wastage, another factor contributing to
      worsening of exercise tolerance.

PMID- 15850575
TI  - White matter abnormalities and gait disorders in older people.

PMID- 15850576
TI  - IL-27 subunits and its receptor (WSX-1) mRNAs are markedly up-regulated in
      inflammatory cells in the CNS during experimental autoimmune encephalomyelitis.
AB  - IL-27 (EBI3p28) is a recently discovered heterodimeric cytokine, which is
      functionally related to IL-23p40p19 and IL-12p40p35. IL-27 acts in synergy with
      IL-12 early during Th1 development from naive T cells. IL-27 functions through
      the WSX-1 and the gpl30 receptor subunits, which shares homology with the IL
      12Rbeta2 subunit. We have previously reported that IL-23 is up-regulated in
      CD11b+ microglia/macrophages in the CNS during the early phase of experimental
      autoimmune encephalomyelitis (EAE), and thus may contribute to the early
      induction of EAE. In the present study, we examined the expression of IL-27 and
      its receptor in the CNS, spleen, and lymph nodes at different stages of EAE
      actively induced with myelin oligodendrocyte glycoprotein peptide(35-55). Our
      findings show that IL-27 EBI3 and p28 mRNA were up-regulated to a maximum level
      at the peak of disease in APC from the CNS and lymph nodes, but not in the
      spleen. Moreover, IL-27 receptor (WSX-1) expression was greatly up-regulated
      during the early stage of EAE in both the CNS and lymph nodes. Taken together,
      our data show that subunits of IL-27 and its receptor (WSX-1) mRNAs are markedly
      up-regulated in inflammatory cells in the CNS at the peak of disease. Thus, IL-27
      produced by infiltrating cells in the CNS may regulate in a paracrine manner the
      Th1 response in EAE.

PMID- 15850577
TI  - Intrahippocampal administration of the branched-chain alpha-hydroxy acids
      accumulating in maple syrup urine disease compromises rat performance in aversive
      and non-aversive behavioral tasks.
AB  - Maple syrup urine disease (MSUD) is an inherited metabolic disease predominantly
      characterized by neurological dysfunction. Although a variable degree of
      psychomotor/delay/mental retardation is found in a considerable number of MSUD
      patients, the mechanisms underlying the neuropathology of this disorder are yet
      not defined. The present study investigated the effect of acute intrahippocampal
      administration of the branched-chain alpha-hydroxy acids (BCHA) accumulating in
      MSUD on rat behavior in non-aversive (open field) and aversive (inhibitory
      avoidance) tasks. Cannulated 60-day-old male Wistar rats received bilateral
      intrahippocampal injection of alpha-hydroxyisocaproic acid (HIC, 1.5 micromol),
      alpha-hydroxyisovaleric acid (HIV, 2.5 micromol), alpha-hydroxy-beta-methyl-n
      valeric acid (HMV, 1.5 micromol), or NaCl (2.5 micromol)(controls) immediately
      after or 10 min before training. Testing session was performed 24 h later.
      Administration of the hydroxy acids immediately after training caused no effect
      on the cognitive performance of the rats. In contrast, HIV and HMV administered
      10 min before training provoked a habituation deficit in the open field task.
      Motor activity, assessed by crossing responses, was the same for the groups
      infused with BCHA and NaCl. The effect of MK-801, succinate, creatine, and the
      antioxidants ascorbic acid plus alpha-tocopherol on the behavioral alterations
      provoked by HIV in the open field task revealed that only the energetic
      substrates (succinate and creatine) prevented these effects, reflecting a
      possible compromise of brain energy production by HIV. We also observed that rats
      pretreated with HIC, HIV, or HMV did not increase their latency in the testing
      session in the step-down inhibitory avoidance task, revealing an impairment of
      retrieval (memory retention or acquisition) in this task. Furthermore, no
      differences between controls and rats receiving BCHA were detected in the latency
      to leave the platform in the training test, suggesting similar motor activity of
      all groups. The data indicate that the alpha-hydroxy acids accumulating in MSUD
      impair cognition and may be implicated in the neuropathology and psychomotor
      delay/mental retardation observed in the affected patients.

PMID- 15850578
TI  - Accrual of MRI white matter abnormalities in elderly with normal and impaired
      mobility.
AB  - White matter signal abnormality (WMSA) is often present in the MRIs of older
      persons with mobility impairment. We examined the relationship between impaired
      mobility and the progressive accrual of WMSA. Mobility was assessed with the
      Short Physical Performance Battery (SPPB) and quantitative measures of gait and
      balance. Fourteen subjects had baseline and follow-up MRI scans performed 20
      months apart. WMSA was detected and quantified using automated computer
      algorithms. In the control subjects, WMSA volume increased by 0.02+/-0.05% ICCV
      (percent intracranial cavity volume)/year while the WMSA of mobility impaired
      subjects increased five-times faster (0.10+/-0.10 ICCV/year, p=0.03). WMSA volume
      was related to some of the mobility measures and was sensitive to change which
      was not true of the other MRI variables. The study demonstrates the sensitivity
      of longitudinal automated volumetric analysis of WMSA to differentiate
      differences in the accrual rate of WMSA in groups selected on the basis of
      mobility. Based on these results, we propose that a subset of subjects with
      mobility impairment have accelerated, disease related WMSA accrual, thus
      explaining the rapid progression of mobility impairment in some older persons
      without apparent cause. This study demonstrates that quantitative MRI and
      performance measures can provide valuable insight into the rate of progression
      and pathophysiologic abnormalities underlying mobility impairment.

PMID- 15850579
TI  - ApaI polymorphism of vitamin D receptor gene is associated with susceptibility to
      HTLV-1-associated myelopathy/tropical spastic paraparesis in HTLV-1 infected
      individuals.
AB  - HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is one
      outcome of human T-cell lymphotropic virus type-1 (HTLV-1) infection. It remains
      unknown why the majority of infected people remain healthy, whereas only
      approximately 2-3% of infected individuals develop the disease. The active form
      of vitamin D has immunomodulatory effects, and allelic variants of the vitamin D
      receptor (VDR) appear to be associated with differential susceptibility to
      several infectious diseases. To investigate whether VDR single nucleotide
      polymorphisms (SNPs) are associated with the development of HAM/TSP, we studied
      four VDR SNPs in a group of 207 HAM/TSP patients and 224 asymptomatic HTLV-1
      seropositive carriers (HCs) in Kagoshima, Japan, by using PCR-RFLP analysis. We
      found that ApaI polymorphism of VDR is associated with the risk of HAM/TSP,
      although this polymorphism did not affect the provirus load of HTLV-1 in either
      HAM/TSP patients or HCs.

PMID- 15850580
TI  - AIDP and CIDP having specific antibodies to the carbohydrate epitope (
      NeuAcalpha2-8NeuAcalpha2-3Galbeta1-4Glc-) of gangliosides.
AB  - Anti-ganglioside antibodies were investigated in plasma exchange solutions (PEs)
      from two patients with acute and chronic inflammatory demyelinating neuropathies
      (AIDP and CIDP). Both cases show markedly elevated antibody titers against the
      lacto-series gangliosides, GM3, GD3, and GT3. In the CIDP patient, the IgG
      antibody titer to GD3 was remarkably elevated (titer, 1:10,000), indicating
      maximal avidity to the tetrasaccharide epitope (-NeuAcalpha2-8NeuAcalpha2
      3Galbeta1-4Glc-). There were also activities toward GM4 and GM2 with the affinity
      higher to GM4 than to GM2, indicating that the antibody activity was not highly
      specific. In contrast, the antibody activities in the AIDP patient showed similar
      avidity to GM3, GD3, and GT3. These two patients are very rare cases that have
      not previously encountered in GBS. The effects on co-cultured cells of rat spinal
      cord and muscle differed according to which PE was used. PE from the AIDP patient
      produced an inhibitory effect (reduction to 26.8%) on the spontaneous muscle
      action potential of the neuromuscular junction (NMJ), but the PE from the CIDP
      patient did not. Thus, in AIDP, the common epitope of GM3, GD3, or GT3 may be
      shared with certain antigens localized in the peripheral nervous system (PNS) and
      may participate in a component of conduction-related molecules in the NMJ. High
      titers of anti-GD3 antibody and the distortion of antibody recognition found in
      CIDP seem to have no immediate effect on electrophysiologic function in the PNS.

PMID- 15850581
TI  - Diffusion-weighted MRI in familial Creutzfeldt-Jakob disease with the codon 200
      mutation in the prion protein gene.
AB  - Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) has been
      reported to be a useful tool for early diagnosis of sporadic Creutzfeldt-Jakob
      disease (CJD). We report MRI findings with DWI, as well as with fluid-attenuated
      inversion recovery (FLAIR) and T1-weighted imaging (T1WI), in a case of familial
      CJD with a mutation at codon 200 of the prion protein gene. DWI in this patient
      showed high signal intensity in the basal ganglia and the cerebral cortex,
      similar to findings in sporadic CJD. In addition, T1WI showed areas of high
      signal intensity bilaterally in the globus pallidus. Despite the clinical
      diversity and atypical laboratory findings seen in familial CJD with the codon
      200 mutation, these neuroimaging studies suggest that common regional
      distributions and a common pathogenesis might underlie the clinical progression
      both in sporadic CJD and in familial CJD with the codon 200 mutation in the prion
      protein gene. DWI abnormalities may be characteristic features that should be
      considered in the diagnosis of familial as well as of sporadic CJD.

PMID- 15850582
TI  - Variability and predictability of functional efficacy of botulinum toxin
      injection in leg spastic muscles.
AB  - Botulinum toxin injection reduces spasticity level. However, the effects on gait
      parameters and daily living activities remain controversial, and the prediction
      of results remains poorly evaluated. The aim of this open study was to
      investigate these effects, and the predictability of results. Forty-seven
      injections were given to 47 patients with stroke (males: 24; mean age: 51.7), in
      the soleus, gastrocnemius, tibialis posterior and anterior, and flexor digitorum
      longus, with a global dose of 300 U (Botox). Each was evaluated at day 1 (D1),
      day 15 (D15), month 2 (M2) and month 5 (M5). We observed a significant but
      moderate reduction in spasticity (Ashworth) of the ankle plantar flexors (0.72/5)
      and dorsiflexors, which was greater at D15, and an improvement in distal
      positioning in the upright situation. Upright balance and gait (Functional
      Ambulation Categories) were improved, especially at M2 and in the barefoot
      condition. Gait velocity and step length with usual aids (10 m) were discretely
      increased, and this was especially evident in about 15 patients. We also found
      improvement in the Rivermead Motor Assessment. Patients reported better foot
      positioning, facilitation in limb propulsion, and better static and dynamic
      balance. For each assessment, high variability in the effects was also shown.
      Improvement in functional tests was partially predicted by age (negative
      relation), delay since stroke (negative relation), gender (better in men),
      spasticity of hip adductors and knee extensors (negative relation), active ankle
      dorsiflexion (positive relation) and heel-ground distance (positive relation). In
      conclusion, the effects on spasticity, balance and gait were relatively modest,
      and with a large variability between patients. Functional improvement could be
      partially predicted by several general or specific factors, the knowledge of
      which is important in the selection of patients to be injected, and for future
      trials aiming to demonstrate the efficacy of botulinum toxin injection.

PMID- 15850583
TI  - Expression of ABCA2 protein in human vestibular schwannoma and peripheral nerve.
AB  - ABCA2, which belongs to the A subclass of the ATP-binding cassette (ABC)
      transporter superfamily, is predominantly expressed in the cytoplasm of
      oligodendrocytes and Schwann cells, the myelin-forming cells in brain and
      peripheral nerve, respectively. Here, we demonstrate by immunoblot and
      immunohistochemistry that ABCA2 is expressed in benign vestibular schwannomas,
      which contain neither axons nor compact myelin. The expression patterns of ABCA2
      in combination with other markers showed phenotypic heterogeneity in schwannomas.
      The majority of cells in fascicular Antoni type A areas coexpressed ABCA2, Ca2+
      binding protein S100beta, and p75 nerve growth factor receptor. In contrast,
      considerably varied expression levels of ABCA2 and p75 were more prominent in
      hypocellular type B areas than in type A areas. These data suggest that ABCA2 may
      be useful as a marker for cellular characterization of schwannomas.

PMID- 15850584
TI  - Utilization of the multiple sclerosis functional composite in follow-up:
      relationship to disease phenotype, disability and treatment strategies.
AB  - As multiple sclerosis (MS) has a dynamic process, monitoring of the disability is
      important in the remission period. The main aim of the present study was to
      investigate the usefulness of MSFC instead of EDSS in the follow-up period of MS.
      In addition, evaluation of the effect of immunomodulatory therapy, and the
      difference among the type of MS in follow-up was purposed. One hundred and eighty
      three patients with definite MS were enrolled in the present study. Patients were
      diagnosed as having relapsing-remitting (RR) MS (n=149) or secondary progressive
      (SP) MS (n=34). Fifty-eight out of 149 RRMS patients who had at least two
      relapses in the last 2 years have received any of the immunomodulator agents. The
      Multiple Sclerosis Functional Composite (MSFC) and Expanded Disability Status
      Scale (EDSS) were performed at baseline and after 2 years to assess disability.
      Patients who were under disease modifying therapy were assessed before the
      treatment and 2 years after starting the treatment. Cross-sectional correlations
      between MSFC and EDSS score at baseline and follow-up were studied. Patients were
      divided into three subgroups: (1) RRMS patients who did not receive disease
      modifying therapy (DMT)--non-DMT group, (2) RRMS patients who received DMT--DMT
      group, (3) SPMS patients who did not receive DMT--SPMS group. EDSS and MSFC
      scores got worsened significantly at the end of the second year. Decreases in
      either EDSS or MSFC scores were more prominent in SPMS group. The most
      significant worsening was found in T25WT. The most prominent and significant
      decrease was in PASAT of SPMS group. Moderately strong cross-sectional
      correlations were found between MSFC and EDSS scores at baseline and follow-up.
      The most prominent correlation was between EDSS and T25WT scores with an
      excellent correlation. We concluded that the MSFC assesses aspects of
      neurological function not measured by the EDSS, suggesting that it is more
      sensitive to detect change over time and better able to demonstrate a therapeutic
      effect. The pattern of correlations among the MSFC, its components, and the EDSS
      supported the validity of MSFC.

PMID- 15850585
TI  - Drop attacks in elderly patients secondary to otologic causes with Meniere's
      syndrome or non-Meniere peripheral vestibulopathy.
AB  - Many neurologists are unaware of the drop attack that may occur from an inner ear
      dysfunction especially in elderly. We studied the clinical features and results
      of quantitative audiovestibular tests in six elderly patients (> or =65 years of
      age) who presented with drop attacks attributable to an inner ear pathology.
      Group was divided into Meniere's syndrome (4) or non-Meniere peripheral
      vestibulopathy (2). Standard dizziness questionnaire and quantitative
      audiovestibular function testing were performed. Episodes were described as a
      sudden push to the ground in four or a violent illusionary movement of
      environment leading to a fall in two. All cases gave a history of prior
      vertiginous episodes and vestibular testing revealed unilateral caloric paresis.
      Ipsilateral hearing loss was documented in four cases. Our results suggest that
      otologic causes should be considered in the differential diagnosis of the drop
      attack in elderly, even if the symptoms and signs were not consistent with
      Meniere's syndrome.

PMID- 15850586
TI  - Transcranial color-coded sonography for vertebrobasilar disorders in end-stage
      renal disease.
AB  - Because vertebrobasilar arterial disorders seem to be common in patients with end
      stage renal disease, a neuroradiological evaluation of vertebrobasilar
      circulation is necessary for patients with possible vertebrobasilar
      insufficiency. In three patients on maintenance hemodialysis, contrast-enhanced
      transcranial color-coded real-time sonography (TCCS) through a suboccipital
      window delineated occlusion of bilateral vertebral arteries with reversal of the
      basilar artery, reversal of the left vertebral artery mimicking left subclavian
      steal phenomenon, and dolichoectasia of the basilar artery and bilateral
      vertebral arteries with signals of turbulent flow. TCCS has several advantages
      over computed tomographic angiography and magnetic resonance angiography,
      including the direction of blood flow, handy performance even during
      hemodialysis, and contrast agent free from nephrotoxicity. Thus, TCCS is useful
      in the evaluation of intracranial circulation in patients with end-stage renal
      disease.

PMID- 15850587
TI  - Distribution of brain atrophy in behavioral variant frontotemporal dementia.
AB  - Marked brain atrophy occurs in frontotemporal dementia (FTD) yet substantial
      variation between cases is seen. Recently, a four-level staging scheme which
      reflects increasing disease duration, severity of dementia and degree of
      neurodegeneration was described. In the present study, the extent and magnitude
      of atrophy in behavioral variant FTD and its relationship to disease duration and
      pathological subtype was further evaluated by quantifying the volume of 30
      anatomically-defined regions. A validated point count technique was applied to 17
      patients with FTD (9 Pick's disease, 6 dementia lacking distinctive histology, 2
      FTD with motor neuron disease) and 21 controls. Atrophy was seen in all brain
      regions except the inferior frontal cortex and area 37. As might be expected,
      increasing severity of atrophy occurred with increasing disease duration and
      stage however measurable atrophy was more widespread than indicated by the
      staging scheme. Furthermore, severity of atrophy was not related to pathological
      subtype. Frontal, limbic and temporal regions appeared to be severely affected
      early in the disease process with temporal lobe atrophy the best predictor of
      disease duration. White matter, more posterior regions and the subcortex were
      affected later in the disease. These findings demonstrate a pattern of selective
      vulnerability which progresses over time. Furthermore, they demonstrate that
      although patients with a similar clinical subtype may have differing underlying
      histopathology, the pattern, severity and progression of brain atrophy is the
      same. This suggests that the regional pattern of neurodegeneration, rather than
      the type of histopathology influences the clinical syndrome in FTD.

PMID- 15850588
TI  - Lack of association between polymorphic microsatellites of the VMAT2 gene and
      Parkinson's disease in Japan.
AB  - The etiology of Parkinson's disease (PD) remains unclear; however, generation of
      reactive oxygen species during oxidation of dopamine (DA) could be one of the
      factors leading to selective loss of nigral dopaminergic neurons in PD. Vesicular
      monoamine transporter type 2 (VMAT2) proteins in nerve terminals uptake and
      partition DA from neuronal cytoplasm into synaptic vesicles. Therefore,
      alterations of VMAT2 function may cause cytoplasmic accumulation of free DA,
      toxic to dopaminergic neurons. Upstream of a putative promoter region of the
      VMAT2 gene, there exist polymorphic sequences consisting of two microsatellites,
      (CA)n and (GA)n. We performed a case-control study of this polymorphic region to
      determine whether the VMAT2 gene is related to PD. We found six genotypes;
      however, there was no significant difference in the allele frequencies between
      patients with PD and control subjects. Our data suggest that the polymorphic
      region of the VMAT2 gene studied here is not closely related to PD.

PMID- 15850589
TI  - Low levels of ALS-linked Cu/Zn superoxide dismutase increase the production of
      reactive oxygen species and cause mitochondrial damage and death in motor neuron
      like cells.
AB  - Mutations of Cu/Zn superoxide dismutase (SOD1) are found in patients with
      familial amyotrophic lateral sclerosis (FALS). A cellular model of FALS was
      developed by stably transfecting the motor neuron-like cell line NSC-34 with
      human wild type (wt) or mutant (G93A) SOD1. Expression levels of G93ASOD1 were
      close to those seen in the human disease. The presence of G93ASOD1 did not alter
      cell proliferation but toxicity was evident when the cells were in the growth
      plateau phase. Flow cytometry analysis indicated that, in this phase, G93ASOD1
      significantly lowered viability and that the level of reactive oxygen species was
      significantly higher in living G93ASOD1 cells compared to wt SOD1 cells.
      Biparametric analysis of mitochondrial membrane potential and viability of
      transfected cells highlighted a peculiar population of damaged cells with strong
      mitochondrial depolarization in the G93ASOD1 cells. Mitochondrial function seemed
      related to the level of the mutant protein since MTT conversion decreased when
      expression of G93ASOD1 doubled after treating cells with sodium butyrate. The
      mutant protein rendered G93ASOD1 cells more sensitive to mitochondrial
      dysfunction induced by stimuli that alter cellular free radical homeostasis, like
      serum withdrawal, depletion of glutathione by ethacrynic acid or rotenone
      mediated inhibition of complex I of the mitochondrial electron transport chain.
      In conclusion, even a small amount of mutant SOD1 put motor neurons in a
      condition of oxidative stress and mitochondrial damage that causes cell
      vulnerability and death.

PMID- 15850590
TI  - Intravascular lymphomatosis presenting with sudden hearing loss.
AB  - Intravascular lymphoma (IVL) is a rare disorder characterized by the aggregation
      of malignant large cell lymphoma cells in small vessels. Neurological
      manifestations are typically the initial and, often the only, clinically obvious
      consequences of this malignancy. Diagnosis is dependent on biopsy or postmortem
      demonstration of the intravascular tumor. We report a patient in whom sudden
      hearing loss heralded IVL and propose that the hearing loss may have been the
      consequence of labyrinthine infarction consequent to the aggregation of malignant
      cells in the internal auditory artery.

PMID- 15850591
TI  - Reversible cortical lesions in primary Sjogren's syndrome presenting with
      meningoencephalitis as an initial manifestation.
AB  - We report a 50-year-old woman with primary Sjogren's syndrome (SjS) who initially
      showed forgetfulness, and later developed disturbance of consciousness. In
      addition to aseptic meningoencephalitis revealed by cerebrospinal fluid
      examination and magnetic resonance imaging (MRI), the presence of serum anti-SS-A
      and anti-SS-B antibodies and inflammatory findings in lip biopsy indicated
      primary SjS. Fluid attenuated inversion recovery (FLAIR) of MRI revealed well
      defined small, high signal intensity areas in the cortex involving the
      subcortical white matter. Corticosteroid therapy resulted in rapid and nearly
      complete resolution of the cortical lesions with marked improvement of the
      clinical manifestations. Memory disturbance is a rare initial manifestation in
      meningoencephalitis associated with SjS. Our patient with SjS showed inflammatory
      cortical lesions on MRI, which were reversed by corticosteroid therapy.

PMID- 15850592
TI  - Recurrent embolic stroke originating from an internal carotid aneurysm in a young
      adult.
AB  - An unruptured intracranial aneurysm is an uncommon but possible embolic source to
      the brain. We report a young patient who developed recurrent ischemic strokes
      occurring mainly in the left internal carotid arterial territory within a short
      interval; the first stroke occurred midway through a long-distance race, and the
      second stroke occurred immediately following a bowel movement. The angiographical
      contrast deficit indicated a thrombus in the left anterior cerebral artery as a
      result of the embolism. A saccular aneurysm of the left distal internal carotid
      artery was the only detectable potential embolic source. Initially anticoagulant
      therapy was given, and then surgical clipping of the aneurysm was performed. The
      patient has been free from stroke recurrence. As a cause of ischemic stroke in
      young adults, a carotid saccular aneurysm should be considered. Hard exercise and
      a Valsalva maneuver may be important triggers of thrombus detachment from the
      aneurysm.

PMID- 15850593
TI  - Peripheral neuropathy associated with chronic natural killer cell lymphocytosis.
AB  - We report a patient with steroid-responsive peripheral neuropathy which developed
      with chronic natural killer cell lymphocytosis (CNKL). A 70-year-old female with
      a 2-week history of progressive motor and sensory neuropathy showed a marked
      increase of natural killer (NK) cells in the blood, and was diagnosed as having
      CNKL. Nerve conduction studies (NCS) revealed a mixed axonal and demyelinating
      neuropathy. A sural nerve biopsy revealed infiltration of NK cells into the nerve
      fascicles, and demyelinating changes with axonal degeneration. The infiltrating
      NK cells were adjacent to myelinated fibers, showing damage of Schwann cell
      membrane. Treatment with oral prednisolone resulted in rapid improvement of the
      sensory disturbance and weakness with a significant decrease of NK cells in the
      blood and disappearance of the conduction blocks in NCS. This is the first case
      of CNKL associated neuropathy in which infiltration of NK cells was demonstrated
      in the nerve fascicles. Our observations suggest that the infiltrating NK cells
      may directly damage myelin and Schwann cells, thus causing demyelination.

PMID- 15850594
TI  - Preventing dyslipidemia by Chlorella pyrenoidosa in rats and hamsters after
      chronic high fat diet treatment.
AB  - The effects of Chlorella pyrenoidosa on serum lipid profiles, after concomitant
      long-term treatment of high-fat diet (HFD) in rats and hamsters was studied.
      Wistar rats and Syrian hamsters were fed with or without various concentrations
      of Chlorella pyrenoidosa contained high-fat diet (CHFD) for 2, 4 and 8 weeks
      prior to assay of serum lipids. Fasting triglycerides, total cholesterol, and LDL
      cholesterol as well as HDL cholesterol levels in high-fat diet treated rats and
      hamster were determined. Results showed that triglycerides, total cholesterol and
      LDL cholesterol levels in HFD treated rats and hamsters were increased from the
      normal rodent diet (NRD) treated controls after 2, 4, and 8-week treatments.
      However, the presence of Chlorella pyrenoidosa in high-fat diets significantly
      decreased the levels of triglycerides, total cholesterol and LDL cholesterol with
      comparison to HFD group in rats and hamsters. The total cholesterol/HDL ratios,
      an indication of occurrence of coronary heart disease, were decreased in all CHFD
      treated grouped rats and hamsters which suggests administration of Chlorella
      pyrenoidosa could lower the occurring risk of heart diseases. In conclusion,
      Chlorella pyrenoidosa has the ability to prevent dyslipidemia in chronic high-fat
      fed animals and could be potential in use to prevent intestinal absorption of
      redundant lipid from our daily intake and subsequently to prevent hyperlipidemia
      as well as atherosclerosis.

PMID- 15850595
TI  - Diazepam augments gender differences in cutaneous LD flux response to local
      cooling.
AB  - Cutaneous vasoconstriction in response to local cooling is normally greater in
      females than in males. Cold induces amplification of alpha2-adrenoceptor affinity
      for norepinephrine and increases reflex sympathetic thermoregulatory output.
      Benzodiazepines are drugs with very well-known binding to the central and
      peripheral benzodiazepine receptors. Besides these effects they decrease
      sympathetic output and as it was shown in the last decade they act
      synergistically with alpha-adrenoceptors. In the present study we tested the
      hypothesis that the benzodiazepine diazepam interacts with an alpha-adrenoceptor
      mechanism at the level of microcirculation. We measured laser-Doppler blood flux
      changes provoked by local cooling before and after oral application of a low dose
      of diazepam (5 mg) in 9 healthy males and in 11 healthy females with regular
      menstrual cycles. The results of our experiments show that in females there is a
      significant reduction (ANOVA, p < 0.05) in laser-Doppler flux during the first
      four minutes of cooling after taking of diazepam. In males, there is no
      significant difference in the responses to cold before and after an application
      of diazepam. Our results suggest that diazepam, in addition to its well-known
      effect on BZ receptors may also interact with alpha2C-adrenoceptors in the vessel
      wall during local cooling.

PMID- 15850596
TI  - Study for anti-angiogenic activities of polysaccharides isolated from Antrodia
      cinnamomea in endothelial cells.
AB  - The main purposes of this study were to investigate the regulation of
      polysaccharides isolated from A. cinnamomea on vascular endothelial growth factor
      (VEGF)-induced cyclin D1 expression and down stream signaling pathway that may
      correlate with their anti-angiogenc effects in endothelial cells (ECs). Crude and
      fractionated polysaccharides (Fra-1 to Fra-4) of A. cinnamomea showed slightly
      toxicity to ECs as compared with their inhibition concentration on angiogenic
      related gene expression. The crude extract and fractionated fractions, except for
      Fra-2, of A. cinnamomea polysaccharides significantly decreased VEGFR2
      phosphorylation on tyrosine 1054/1059, cyclin D1 promotor activity, and protein
      expression induced by VEGF. Crude extract of A. cinnamomea polysaccharides
      inhibited the binding of VEGF to KDR/flk-1 in a dose-dependent manner. These
      results indicated that inhibition of VEGF interaction with VEGF receptor 2 is the
      mechanism serves A. cinnamomea as a protective mechanism composing the anti
      angiogenesis function. Furthermore, A. cinnamomea polysaccharides also blocked
      VEGF-induced migration and capillary-like tube formation of ECs on Matrigel.
      Taken together, these results indicate that A. cinnamomea polysaccharides inhibit
      cyclin D1 expression through inhibition of VEGF receptor signaling, leading to
      the suppression of angiogenesis.

PMID- 15850597
TI  - Anti-oxidative stress effects of Herba leonuri on ischemic rat hearts.
AB  - Our current study was to test the hypothesis that the extract of Herba leonuri
      (HL) would have antioxidant and cardioprotective effects on ischemic myocardium.
      The extract of HL (400 mg/kg/day) was administered orally (daily) starting from 1
      week before and continuing until 3 weeks after myocardial infarction (MI).
      Surviving rats were sacrificed at different time points to obtain left ventricles
      for biochemical assays. Our study demonstrates for the first time that HL does
      have antioxidant effects both in vitro and in vivo. The antioxidant effects of HL
      are exerted only under the condition of oxidative stress, by selectively
      preserving the activities of superoxide dismutase and glutathione peroxidase, as
      well as depressing the formation of malondialdehyde, especially in the acute
      phase of acute MI. Its effects of scavenging free radicals and inhibiting the
      formation of reactive oxygen species may play a key role in protecting the
      endogenous antioxidant system from oxidative stress in vivo.

PMID- 15850598
TI  - Long term phenobarbital administration does not promote the multiplication of
      hepatocytes replicating after single cyproterone acetate administration.
AB  - Cyproterone acetate (CPA) is a synthetic antiandrogenic compound which is widely
      used in clinic but suspected to be hepatocarcinogenic. CPA is also mitogenic in
      rat liver. Using genetic labeling of dividing cells, we examined whether
      hepatocytes dividing in response to acute CPA administration could give rise to
      preneoplastic foci after administration of a tumor promoter: phenobarbital. CPA
      was administered orally to rats and dividing hepatocytes were genetically labeled
      using retroviral vectors carrying the beta-galactosidase gene. After labeling
      rats were given phenobarbital for 10 months and sacrificed. The presence of beta
      galactosidase labeled hepatocytes as well as preneoplastic hepatocytes was
      assessed by immunohistochemistry. Genetic labeling of hepatocytes was obtained in
      all animals. At the end of phenobarbital administration, no hepatic tumors were
      observed. Preneoplastic foci were not increased in treated animals as compared to
      control rats. Moreover beta-galactosidase positive hepatocytes were never
      detected in preneoplastic foci. Finally, the size of the beta-galactosidase
      positive clusters was smaller in treated animals as compared to control rats. We
      conclude that acute CPA administration is not carcinogenic in rat liver and does
      not initiate preneoplastic hepatocytes capable to give rise to foci after
      phenobarbital promotion. Therefore the mitogenic property of CPA is distinct from
      its putative carcinogenic activity. Finally, analysis of the size of beta
      galactosidase positive cells clusters demonstrate that phenobarbital does not
      induce hepatocyte proliferation in rats.

PMID- 15850599
TI  - Hypoglycemic effect of crude exopolysaccharides produced by a medicinal mushroom
      Phellinus baumii in streptozotocin-induced diabetic rats.
AB  - The antidiabetic effect of the crude exopolysaccharides (EPS) produced from
      submerged mycelial culture of Phellinus baumii in streptozotocin (STZ)-induced
      diabetic rats was investigated. The produced EPS consisted of two different
      heteropolysaccharides and two proteoglycans. The food intake of the diabetic
      control rats (STZ) was increased by 28.1%, whereas body weight gain was reduced
      by 44.1% as compared to the nondiabetic animals (NC). The plasma glucose level in
      the EPS-fed rats (EPS) was substantially reduced by 52.3% as compared to the
      diabetic rats (STZ), which is the highest hypoglycemic effect among mushroom
      derived materials documented in literature. The activities of alanine
      aminotransferase (ALT) and asparate aminotransferase (AST) were significantly
      decreased by administration of P. baumii EPS, thereby exhibiting a remedial role
      in liver function. The significant increase in weights of liver, spleen, and
      kidney was observed in diabetic groups (both STZ and EPS) compared to NC. The
      results suggest that orally administrated P. baumii EPS exhibited considerable
      hypoglycemic effect in STZ-induced diabetic rats and that these EPS may be useful
      for the management of diabetes mellitus.

PMID- 15850601
TI  - Pharmacological basis for the use of turmeric in gastrointestinal and respiratory
      disorders.
AB  - This study was carried out to provide scientific basis for the medicinal use of
      turmeric (Curcuma longa) in gastrointestinal and respiratory disorders. The crude
      extract of turmeric (Cl.Cr), relaxed the spontaneous and K+ (80 mM)-induced
      contractions in isolated rabbit jejunum as well as shifted the CaCl2
      concentration-response curves. In rabbit tracheal preparation, Cl.Cr inhibited
      carbachol and K(+)-induced contractions. In anesthetized rats, Cl.Cr produced
      variable responses on blood pressure with a mixture of weak hypertensive and
      hypotensive actions. In rabbit aorta, Cl.Cr caused a weak vasoconstrictor and a
      vasodilator effect on K+ and phenylephrine-induced contractions. In guinea-pig
      atria, Cl.Cr inhibited spontaneous rate and force of contractions at 14-24 times
      higher concentrations. Activity directed fractionation revealed that the
      vasodilator and vasoconstrictor activities are widely distributed in the plant
      with no clear separation into the polar or non-polar fractions. When used for
      comparison, both curcumin and verapamil caused similar inhibitory effects in all
      smooth muscle preparations with relatively more effect against K(+)-induced
      contractions and that both were devoid of any vasoconstrictor effect and curcumin
      had no effect on atria. These data suggest that the inhibitory effects of Cl.Cr
      are mediated primarily through calcium channel blockade, though additional
      mechanism cannot be ruled out and this study forms the basis for the traditional
      use of turmeric in hyperactive states of the gut and airways. Furthermore,
      curcumin, the main active principle, does not share all effects of turmeric.

PMID- 15850600
TI  - The theaflavin fraction is responsible for the facilitatory effect of black tea
      at the skeletal myoneural junction.
AB  - The effect of various fractions of black tea [(Camellia Sinensis) (L) O. Kuntze
      (Theaceae)] on the function of mammalian skeletomotor apparatus was studied. The
      theaflavin fraction (Tfs) produced a concentration- dependent facilitation of
      indirect twitch responses of the rat phrenic nerve diaphragm preparation and the
      facilitation was dependent on the amount of calcium present in the bathing fluid.
      Nifedipine reduced the facilitatory effect of Tfs as a function of its
      concentration. Tfs failed to produce facilitation when the twitch height was
      reduced to about 50% of the control value in presence of magnesium chloride. Tfs
      completely antagonized the submaximal paralytic effect of d- tubocurarine and
      decamethonium bromide. Tfs did not have any effect on direct twitch responses or
      on acetylcholine (Ach) and potassium chloride (KCl) induced contractures of
      denervated diaphragm. The results revealed that the site of action of Tfs is on
      the contractile mechanism of the voluntary muscle and point to a critical role of
      calcium in the mechanism of action of Tfs. N omega-nitro-L-arginine-methyl ester
      (L-NAME), a nitric oxide synthase (NOS) inhibitor, antagonized both the
      facilitatory and inhibitory effects on indirect twitch responses of rat diaphragm
      induced by L-arginine and Tfs when the phrenic nerve was stimulated at 5 Hz and
      50 Hz respectively. The thearubigin (Trs) fraction of black tea and the aqueous
      part which is completely devoid of Tfs, did not potentiate the twitch responses.
      The findings suggest that Tfs have a potentiating effect on the contractile
      mechanism of skeletal muscle and that calcium and nitric oxide may modulate this
      action of Tfs.

PMID- 15850602
TI  - Carbamazepine is an inhibitor of histone deacetylases.
AB  - Carbamazepine (CBZ) is a common antiepileptic drug (AED) that acts through
      multiple mechanisms including blockade and potentiation of cation channels and
      modulation of neurotransmitter levels. Whether it affects any component of the
      gene transcription machinery is unknown. Histone deacetylases (HDAC) are
      important in the regulation of gene expression and are currently considered a
      potential target for drug development. Using a high-throughput screening assay
      based on acetylation-dependent gene expression, we identified CBZ as a candidate
      and proceeded to characterize its effects on HDAC. CBZ induced acetylation of
      histone H4 in the HepG2 liver carcinoma cell line. CBZ inhibited HDAC 3 and HDAC
      7, which are representatives of HDAC class I and II respectively. Quantitative
      testing in an in vitro assay demonstrated HDAC inhibition with an IC50 of 2
      microM. The major active metabolite of CBZ, CBZ-10,11-epoxide, was found to have
      the same HDAC inhibitory activity. The IC50 is considerably lower than
      therapeutic plasma levels that are typically achieved in patients (25-51 microM).
      CBZ shares important clinical characteristics (teratogenicity, activity as a mood
      stabilizer) with valproic acid, another AED that was recently identified as an
      inhibitor of HDAC. These observations raise the possibility that HDAC inhibition
      may contribute to the pharmacological profile of CBZ.

PMID- 15850603
TI  - Short-term effects of estrogen, tamoxifen and raloxifene on hemostasis: a
      randomized-controlled study and review of the literature.
AB  - INTRODUCTION: Estrogen therapy (ET), tamoxifen and raloxifene are associated with
      a two- to three-fold increased risk of venous thrombosis (VT); however, the
      mechanisms by which each drug increases venous thrombosis propensity are not
      fully understood. The objectives of this investigation were to compare the
      effects of these three treatments on hemostasis in a head to head randomized
      placebo-controlled trial. PATIENTS/METHODS: Ninety-four postmenopausal women were
      assigned to receive oral estrogen (conjugated equine estrogen [CEE] 0.625 mg,
      n=23), tamoxifen 20 mg (n=24), raloxifene 60 mg (n=24) or placebo (n=23) daily
      for 6 months. Blood samples were analyzed for procoagulant factors (prothrombin,
      factors VII [fVII], VIII [fVIII], IX [fIX] and XI [fXI], D-dimer and von
      Willebrand factor [vWf]), anticoagulant factors (antithrombin [AT], total and
      free protein S, protein C and activated protein C [APC] resistance) and
      fibrinolytic factors (thrombin activatable fibrinolysis inhibitor [TAFI] and
      plasminogen activator inhibitor-1 [PAI-1]), at baseline and at 6 months of
      treatment. RESULTS: Estrogen increased factor VII and D-dimer, and decreased
      antithrombin, total and free protein S and PAI-1. Changes with tamoxifen were
      distinct from estrogen with increases in factors VIII, IX, vWf and free protein
      S, and decreases in AT, total protein S, protein C and plasminogen activator
      inhibitor-1. Raloxifene produced similar effects as tamoxifen, but did not
      increase factor IX or decrease protein C. CONCLUSIONS: Estrogen, tamoxifen and
      raloxifene affected hemostasis favoring procoagulation and impairing
      anticoagulation. The biochemical effects of the selective estrogen receptor
      modulators (SERMs) were distinct from those of estrogen and differed only subtly
      from each other.

PMID- 15850604
TI  - Protein C levels can be forecasted by global haemostatic tests in critically ill
      patients and predict long-term survival.
AB  - INTRODUCTION: We have shown the usefulness of global haemostatic tests
      International Normalized Ratio (INR) and Activated Partial Thromboplastin Time
      (APTT) for predicting survival in critically ill patients. Ability to analyse
      inhibitors protein C and antithrombin is limited to a small number of
      laboratories and often only during office hours. We therefore studied the
      usefulness of global haemostatic tests to predict levels of protein C and
      antithrombin and investigated value of these latter tests in predicting outcome.
      PATIENTS/METHODS: Blood samples were collected within 6 h of admission to
      intensive care unit (ICU) and tested regarding platelet count, INR, and APTT. If
      platelet count was <100x10(9) L(-1), INR >1.36 and/or APTT >45 s, a second
      sampling was done within 6 h after the first one for analysis of protein C and
      antithrombin. Ninety-two patients were included; length of stay at ICU and
      hospital, survival when leaving ICU and hospital and up to 5 years were recorded.
      RESULTS: Using univariate analysis of variance, INR and APTT separately predicted
      levels of protein C and to some extent antithrombin. Neither platelet count nor
      any combinations of global haemostatic tests were predictive. Utilising Cox
      regression, decreased protein C, but not antithrombin, predicted lower survival
      rate. CONCLUSIONS: Global haemostatic tests INR and APTT can predict levels of
      protein C and, though less so, antithrombin. A low protein C level indicated a
      sinister prognosis in the ICU setting, at the hospital, and after up to 5 years.

PMID- 15850605
TI  - Platelet reactivity in response to mental stress in syndrome X and in stable or
      unstable coronary artery disease.
AB  - INTRODUCTION: Previous studies showed differences in platelet reactivity in
      response to exercise in patients with syndrome X (SX) and those with obstructive
      coronary artery disease (CAD). In this study, we investigated whether similar
      differences could be detectable in response to a mental stressful stimulus.
      MATERIALS AND METHODS: We studied 30 SX patients (60+/-8 years, 8 men), 20
      patients with stable angina and angiographically documented CAD (SA, 66+/-8
      years, 14 men), and 11 patients with unstable angina (UA, 67+/-8 years, 6 men). A
      control group of 22 healthy controls (50+/-7 years, 5 men) was also studied. All
      subjects underwent a mathematical mental stress test (MST) consisting of rapid
      consecutive subtractions of number 7 for a period of 5 min. A venous blood sample
      was collected at baseline and immediately after MST. Platelet reactivity was
      measured on flowing blood as time necessary to occlude a ring coated with
      collagen-adenosine diphosphate (ADP; closure time, CT), using the platelet
      function analyzer (PFA-100) system. RESULTS: At rest, CT was lower in UA patients
      (87+/-19 s) compared to controls (109+/-24 s, p=0.02) and SA patients (105+/-37
      s, p=0.055), and also tended to be lower in SX patients (96+/-18 s) compared to
      controls (p=0.07). The CT response to MST differed significantly among groups
      (p=0.0009). At peak MST, CT did not change in controls (110+/-27 s, p=0.88),
      whereas it decreased in SA patients (96+/-29 s, p=0.003) and tended to decrease
      in UA patients (82+/-15 s, p=0.25). In contrast, a significant increase in CT
      with MST was shown in SX patients (103+/-21 s, p=0.007). CONCLUSIONS: Platelet
      reactivity is increased by MST in patients with CAD, whereas it paradoxically
      decreases in SX patients, which may constitute a protective effect against stress
      induced events in these patients.

PMID- 15850606
TI  - The impact of cardiac ischemia and reperfusion on markers of activated
      haemostasis and fibrinolysis during cardiopulmonary bypass: comparison of plasma
      levels in arterial and coronary venous blood.
AB  - INTRODUCTION: Activation of coagulation and fibrinolysis is common among patients
      undergoing cardiopulmonary bypass (CPB) surgery. Little is known, however, about
      the impact of myocardial ischemia and reperfusion on coagulation activation and
      fibrinolysis in this clinical setting. STUDY DESIGN AND METHODS: We determined
      the levels of coagulation activation and fibrinolysis markers (CAFM) in 19
      patients with severe coronary heart disease (CHD) during CPB surgery. FXIIa,
      tissue factor (TF), FVIIa, tissue plasminogen activator/plasminogen activator
      inhibitor-1 complexes (tPA/PAI-1), prothrombin fragments 1+2 (F1+2), D-dimers
      (DD) and plasmin-plasmin inhibitor complexes (PPI) were measured at baseline,
      prior to and after cardioplegic myocardial ischemia. Simultaneous blood samples
      were drawn from the aorta and the coronary sinus to evaluate arteriovenous CAFM
      plasma level gradients. RESULTS: Myocardial ischemia induced significant
      increases in gradients of FXIIa and F1+2 levels across the coronary circulation
      without influencing systemic levels of these markers significantly. Systemic
      levels of FXIIa, tPA/PAI-1, F1+2, DD and PPI increased significantly during CPB
      operation. There was a significant linear correlation between FXIIa, FVIIa, F1+2,
      DD and PPI. CONCLUSIONS: Myocardial ischemia induces contact activation and
      thrombin generation rather than release of tPA and might thus contribute to
      postoperative thromboembolic complications. Surgery itself and CPB cause
      activation of coagulation and fibrinolysis as already described. A significant
      association between FXIIa, FVIIa, F1+2, DD and PPI suggests a relationship
      between contact activation, thrombin generation, fibrin formation and
      fibrinolysis.

PMID- 15850607
TI  - Dosage of enoxaparin among obese and renal impairment patients.
AB  - BACKGROUND: Enoxaparin dosage for obese patients and patients with renal
      impairment remains controversial. OBJECTIVE: To compare anti-factor Xa activity
      (anti-Xa) among obese and renal impairment patients to patients with healthy
      weight and adequate renal function. DESIGN: Open, prospective, nonrandomized
      clinical trial. SETTING: A major community teaching hospital. PATIENTS: A total
      of 233 patients with prescription of enoxaparin. INTERVENTIONS: Enoxaparin 1.5
      mg/kg once daily or 1 mg/kg twice daily except those on dialysis, who received
      75% of the dose. MEASUREMENTS: Anti-Xa was measured 4 h post-injection on day 2
      or 3. RESULTS: Mean (95% confidence interval (95% CI)) anti-Xa was equal to 1.14
      IU/mL (1.07-1.21) and 1.14 IU/mL (1.08-1.20) among patients who received one
      (n=92) and two injections (n=122) per day, respectively. Anti-Xa increases with
      body mass index (BMI) (0.01 IU/mL for each kg/m2; 95% CI: 0.002-0.017), but the
      increase is insufficient to reach supratherapeutic anti-Xa. Anti-Xa decreases
      with higher creatinine clearance (CrCl) (-0.003 IU/mL for each mL/min; 95% CI: 
      0.006 to -0.001). On the twice-daily regimen, this is sufficient to reach
      supratherapeutic anti-Xa. The odd ratio (OR) (95% CI) of having a nontherapeutic
      anti-Xa is equal to 2.28 (1.25-4.16) when enoxaparin is administered twice daily
      and to 3.03 (1.16-7.86) among severe renal impairment patients (< or =30 mL/min).
      CONCLUSIONS: Based on Anti-Xa, no dosage adjustments are required in obese
      patients. In renally impaired patients, adjustments may be necessary when
      enoxaparin is administered twice daily.

PMID- 15850608
TI  - Lack of thrombopoietin potentiation of platelet collagen activation in the first
      trimester is associated with preeclampsia.
AB  - To determine whether a difference exists in platelet reactivity to collagen and
      potentiation by thrombopoietin (TPO) between preeclamptic and non-preeclamptic
      patients, 187 first trimester pregnant patients were prospectively followed
      through pregnancy. Citrated blood, drawn at first (<14 weeks estimated
      gestational age) and third trimesters (>28 weeks), when patients were admitted
      for delivery, and 4-6 weeks postpartum, was assayed by a Whole Blood Impedance
      Aggregometer measuring platelet activation by 0.4 mug/ml collagen, +/-10 ng/ml
      TPO. There was no significant difference in 1st trimester platelet collagen
      activation by unpaired t-test between groups. Significant TPO potentiation of
      collagen activation (P<0.05, paired t-test) was observed in non-preeclamptic
      patients at the first and third trimesters. In contrast, preeclamptic patients'
      platelets show no significant (P>0.8, paired t-test) TPO potentiation at any
      time. While the mechanism for this difference in thrombopoietin potentiation of
      platelet activation by collagen as early as the first trimester is unknown, it
      may be one of the initiating events in this syndrome.

PMID- 15850609
TI  - Pharmacodynamics and pharmacokinetics of the platelet GPIIb/IIIa inhibitor
      tirofiban in patients undergoing percutaneous coronary intervention: implications
      for adjustment of tirofiban and clopidogrel dosage.
AB  - INTRODUCTION: Despite extensive data supporting the use of platelet glycoprotein
      (GP) IIb/IIIa (GPIIb/IIIa) inhibitors in the therapy of patients with acute
      coronary syndromes (ACS), there is considerable debate as to the optimal choice
      of antiplatelet regimen. The objective of this study was to conduct a detailed
      time-resolved analysis of the effects of the GPIIb/IIIa inhibitor tirofiban with
      concomitant clopidogrel in ACS patients undergoing percutaneous coronary
      intervention (PCI) to improve the dosing regimen of these two commonly used
      antiplatelet drugs. METHODS: The study was performed in 14 patients with non-ST
      segment elevation (NSTE) ACS who underwent PCI while being treated with the
      current typically utilized regimen of tirofiban (10 microg/kg bolus, 0.15
      microg/kg/min infusion) and clopidogrel (300 mg). Platelet function was assessed
      before, during, and after tirofiban infusion using a panel of agonists for ADP
      receptors, PAR1 and PAR4 thrombin receptors, and collagen receptors. RESULTS:
      Measurements of circulating tirofiban levels demonstrated a trough, which
      paralleled a reduction in platelet inhibition for all platelet agonists during
      the time when PCI was being performed. Interestingly, younger ACS patients (<55
      years) exhibited less inhibition of platelet function both during the PCI
      procedure and after termination of the tirofiban infusion. These apparent age
      differences were primarily attributed to a decreased responsiveness of the
      younger patients to clopidogrel. CONCLUSIONS: This study shows that the currently
      utilized tirofiban dosage is suboptimal and suggests that patients may benefit
      from a higher dose regimen.

PMID- 15850610
TI  - Thrombin stimulation of Cl-/HCO3- exchange in human platelets.
AB  - The presence of one acidifying Cl-/HCO3- exchange mechanism in human platelets
      has not been previously reported. This paper demonstrates that this mechanism
      does function and that it increases its activity after stimulation with thrombin.
      On resuspension of BCECF-loaded platelets in a chloride-free medium (gluconate
      replaced) that contains bicarbonate, cytosolic pH (pHi) increased and stabilized
      after 10 min at an alkaline value. After addition of 50 mM NaCl, pHi fell rapidly
      reaching steady state in the succeeding 5 min. The stilbene derivative 4
      acetamido-4'-isothiocyanato stilbene-2,2' disulfonic acid (SITS) inhibited both,
      the alkalization in chloride-poor solution and the recovery from the alkaline
      load after chloride enrichment. The decline in pHi was observed whether chloride
      was delivered to the solution in the form of LiCl or NaCl, or when the later was
      applied after blockage of the Na+/H+ exchanger. The recovery in chloride
      containing solution was in contrast to the effect of a similar change in
      osmolarity by addition of 50 mM sodium gluconate that did not produced a
      significant variation of pHi. Posterior addition of NaCl after 5 min in high
      gluconate reproduced the pHi fall of the control experiment. Alkali loads
      produced by 25 mM trimethylamine hydrochloride (TMA) were also counteracted by
      HCO(3-)-equivalent efflux via Cl-/HCO3- exchange. One of the major observations
      of the present study is that HCO3- equivalent efflux was twice as high when the
      platelets were previously stimulated with 0.1 IU of thrombin, but thrombin did
      not produce significant changes of the pHi recovery rate in a bicarbonate-free
      solution. The increase of the decline in pHi elicited by preexposure to thrombin
      was still observed in the presence of an inhibitor of the Na+/H+ exchange or in
      sodium-free solutions. It is concluded that a Na-independent Cl-/HCO3- exchange
      mechanism mediates the recovery of pHi from alkalosis in platelets and that
      thrombin activates this exchanger by a direct regulatory pathway.

PMID- 15850611
TI  - Characterization of recombinant murine factor VIIa and recombinant murine tissue
      factor: a human-murine species compatibility study.
AB  - Tissue factor (TF) is believed to play an important role in coagulation,
      inflammation, angiogenesis and wound healing as well as in tumor growth and
      metastasis. To facilitate in vivo studies in experimental murine models, we have
      produced recombinant murine factor VII (FVII) and the ectodomain of murine TF,
      TF(1-223). Murine FVII was activated to FVIIa with human factor Xa and upon
      reaction with FFR-chloromethyl ketone converted into an active site-blocked TF
      antagonist, FFR-FVIIa. The activity of murine FVIIa was characterized in factor X
      activation assays as well as in clot assays with murine and human thromboplastin
      in murine and human plasma. In these assays murine FVIIa exhibited a specific
      activity equivalent to or higher than human FVIIa. Further analysis showed that
      murine FVIIa binds with high affinity to both murine and human TF, whereas the
      association of human FVIIa to murine TF is about three orders of magnitude weaker
      than the association to human TF. This difference was further emphasized by the
      effect of murine-and human FFR-FVIIa on bleeding in an in vivo mouse model. Intra
      peritoneal administration of 1 mg/kg murine FFR-FVIIa significantly prolonged the
      tail-bleeding time, whereas no effect on bleeding was observed with a 25-times
      higher dose of the human FFR-FVIIa. Together, these data confirms the notion of
      poor species compatibility between human FVII and murine TF and emphasizes the
      requirement for autologous FVIIa in studies on the role of the TF in experimental
      in vivo pharmacology.

PMID- 15850612
TI  - Acquired factor V inhibitor and single exposure to autologous growth factor.

PMID- 15850613
TI  - Effectiveness trials in African children with malaria?

PMID- 15850614
TI  - Presumptive malaria treatment in immunisation programmes.

PMID- 15850615
TI  - Aortic wall thickening in utero.

PMID- 15850616
TI  - Death after withdrawal of nutrition and hydration.

PMID- 15850617
TI  - PSA testing: what is the use?

PMID- 15850618
TI  - Preventing cancer, cardiovascular disease, and diabetes.

PMID- 15850619
TI  - Random mandatory drugs testing of prisoners.

PMID- 15850621
TI  - Immunity.

PMID- 15850622
TI  - The Commission for Africa: a recipe for success?

PMID- 15850623
TI  - The Commission for Africa: a recipe for success?

PMID- 15850624
TI  - Income inequality and nations' altruism.

PMID- 15850625
TI  - Seeking a safer blood supply.

PMID- 15850626
TI  - CT colonography for detection of colon polyps and cancer.

PMID- 15850627
TI  - Seeking a safer blood supply.

PMID- 15850629
TI  - Fingerprint identification of AIDS patients on ART.

PMID- 15850630
TI  - Supervised versus unsupervised intake of six-dose artemether-lumefantrine for
      treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara,
      Uganda: a randomised trial.
AB  - BACKGROUND: The six-dose regimen of artemether-lumefantrine is effective and is
      among combination therapies prioritised to replace antimalarials that no longer
      work in Africa. However, its effectiveness has not been assessed in the field,
      and could be compromised by poor adherence, incorrect timing of doses, and
      insufficient intake of fatty foods with every dose. Our aim, therefore, was to
      assess the effectiveness of artemether-lumefantrine prescribed under routine
      outpatient conditions, compared with its efficacy when given under supervision to
      inpatients with acute uncomplicated falciparum malaria. METHODS: We did a
      randomised trial to compare the efficacy, safety, and pharmacokinetics of
      artemether-lumefantrine when given in a supervised (all doses observed with fatty
      food intake; n=313) or unsupervised (first dose supervised followed by outpatient
      treatment with nutritional advice; n=644) setting to patients of all ages (weight
      >10 kg) with acute, uncomplicated falciparum malaria in Mbarara, Uganda. Our
      primary endpoint was 28 day, PCR-adjusted, parasitological cure rate. Analysis
      was by intention to treat and evaluability analysis. FINDINGS: 38 patients were
      lost to follow-up and one withdrew consent. Day-28 cure rates were 97.7% (296 of
      303) and 98.0% (603 of 615) in the supervised and unsupervised groups,
      respectively. We recorded 15 non-severe, drug-related adverse events, all of
      which resolved. INTERPRETATION: Artemether-lumefantrine has a high cure rate
      irrespective of whether given under supervision with food or under conditions of
      routine clinic practice. If used as first-line treatment, artemether-lumefantrine
      could make a substantial contribution to malaria control in Africa, though cost
      is an issue.

PMID- 15850631
TI  - Amodiaquine alone, amodiaquine+sulfadoxine-pyrimethamine, amodiaquine+artesunate,
      and artemether-lumefantrine for outpatient treatment of malaria in Tanzanian
      children: a four-arm randomised effectiveness trial.
AB  - BACKGROUND: Many countries in Africa are considering a change to combination
      treatment for falciparum malaria because of the increase in drug resistance.
      However, there are few effectiveness data for these combinations. Our aim was to
      study the effectiveness of three drug combinations that have proven efficacious
      in east Africa compared with amodiaquine monotherapy. METHODS: We undertook a
      randomised trial of antimalarial drug combinations for children (aged 4-59
      months) with uncomplicated malaria in Muheza, Tanzania, an area with a high
      prevalence of resistance to sulfadoxine-pyrimethamine and chloroquine. Children
      were randomly allocated 3 days of amodiaquine (n=270), amodiaquine +sulfadoxine
      pyrimethamine (n=507), or amodiaquine+artesunate (n=515), or a 3-day six-dose
      regimen of artemether-lumefantrine (n=519). Drugs were taken orally, at home,
      unobserved by medical staff. The primary endpoint was parasitological failure by
      day 14 assessed blind to treatment allocation. Secondary endpoints included day
      28 follow-up and gametocyte carriage. Analysis was by intention to treat.
      FINDINGS: Of 3158 children screened, 1811 were randomly assigned treatment and
      1717 (95%) reached the 14-day follow-up. The amodiaquine group was stopped early
      by the data and safety monitoring board. By day 14, the parasitological failure
      rates were 103 of 248 (42%) for amodiaquine, 97 of 476 (20%) for
      amodiaquine+sulfadoxine-pyrimethamine, 54 of 491 (11%) for
      amodiaquine+artesunate, and seven of 502 (1%) for artemether-lumefantrine. By day
      28, the parasitological failure rates were 182 of 239 (76%), 282 of 476 (61%),
      193 of 472 (40%), and 103 of 485 (21%), respectively. The difference between
      individual treatment groups and the next best treatment combination was
      significant (p<0.001) in every case. Recrudescence rates by day 28, after
      correction by genotyping, were 48.4%, 34.5%, 11.2%, and 2.8%, respectively.
      INTERPRETATION: The study shows how few the options are for treating malaria
      where there is already a high level of resistance to sulfadoxine-pyrimethamine
      and amodiaquine. The WHO-packaged six-dose regimen of artemether-lumefantrine is
      effective taken unsupervised, although cost is a major limitation.

PMID- 15850632
TI  - Intermittent preventive antimalarial treatment for Tanzanian infants: follow-up
      to age 2 years of a randomised, placebo-controlled trial.
AB  - Stopping antimalarial chemoprophylaxis can be followed by increased risk of
      malaria, suggesting that it interferes with the development of antimalarial
      immunity. We report analysis of extended follow-up until age 2 years of a
      randomised, placebo-controlled double-blind trial of intermittent preventive
      antimalarial treatment in infants. The rate of clinical malaria (events per
      person-year at risk, starting 1 month after final dose of intermittent treatment)
      was 0.28 in the sulfadoxine-pyrimethamine group and 0.43 in the placebo group
      (protective effect 36%, 95% CI 11-53). Intermittent treatment produced a
      sustained reduction in the risk of clinical malaria extending well beyond the
      duration of the pharmacological effects of the drugs, excluding a so-called
      rebound effect and suggesting that such treatment could facilitate development of
      immunity against Plasmodium falciparum.

PMID- 15850634
TI  - Malaria.
AB  - Malaria is the most important parasitic infection in people, accounting for more
      than 1 million deaths a year. Malaria has become a priority for the international
      health community and is now the focus of several new initiatives. Prevention and
      treatment of malaria could be greatly improved with existing methods if increased
      financial and labour resources were available. However, new approaches for
      prevention and treatment are needed. Several new drugs are under development,
      which are likely to be used in combinations to slow the spread of resistance, but
      the high cost of treatments would make sustainability difficult. Insecticide
      treated bed-nets provide a simple but effective means of preventing malaria,
      especially with the development of longlasting nets in which insecticide is
      incorporated into the net fibres. One malaria vaccine, RTS,S/AS02, has shown
      promise in endemic areas and will shortly enter further trials. Other vaccines
      are being studied in clinical trials, but it will probably be at least 10 years
      before a malaria vaccine is ready for widespread use.

PMID- 15850633
TI  - Aortic wall thickness in newborns with intrauterine growth restriction.
AB  - Much epidemiological evidence has linked low birthweight with late cardiovascular
      risk. We measured aortic wall thickness (a marker of early atherosclerosis) by
      ultrasonography in 25 newborn babies with intrauterine growth restriction and 25
      with normal birthweight. Maximum aortic thicknesses were significantly higher in
      the babies with intrauterine growth restriction (810 microm [SD 113]) than in
      those without (743 microm [76], p=0.02), more so after adjustment for birthweight
      (300 microm/kg [45] vs 199 microm/kg [29], p<0.0001). Newborn babies with growth
      restriction have significant aortic thickening, suggesting that prenatal events
      might predispose to later cardiovascular risk.

PMID- 15850635
TI  - Do as I say, not as I do.

PMID- 15850636
TI  - Refining clinical diagnosis with likelihood ratios.
AB  - Likelihood ratios can refine clinical diagnosis on the basis of signs and
      symptoms; however, they are underused for patients' care. A likelihood ratio is
      the percentage of ill people with a given test result divided by the percentage
      of well individuals with the same result. Ideally, abnormal test results should
      be much more typical in ill individuals than in those who are well (high
      likelihood ratio) and normal test results should be most frequent in well people
      than in sick people (low likelihood ratio). Likelihood ratios near unity have
      little effect on decision-making; by contrast, high or low ratios can greatly
      shift the clinician's estimate of the probability of disease. Likelihood ratios
      can be calculated not only for dichotomous (positive or negative) tests but also
      for tests with multiple levels of results, such as creatine kinase or ventilation
      perfusion scans. When combined with an accurate clinical diagnosis, likelihood
      ratios from ancillary tests improve diagnostic accuracy in a synergistic manner.

PMID- 15850637
TI  - Malaria control in Afghanistan: progress and challenges.
AB  - From the 1950s until 1979 malaria control in Afghanistan was implemented through
      a vertical programme managed by the government, but little of the original
      programme remained functional by the early 1990s. Delivery of basic health care
      including malaria diagnosis and treatment was done by non-governmental
      organisations (NGOs) and UN agencies, which organised cross-border operations
      from Pakistan and Iran and placed much less emphasis on vertical programming.
      From 1992 the situation in the east of Afghanistan became stable enough to allow
      the establishment of a network of NGO-supported clinics and to introduce
      standardised training and monitoring of microscopists and clinical staff,
      coordinated by a lead agency specialising in malaria. After the collapse of the
      Taliban in 2001 and the subsequent establishment of an interim government, the
      first steps in health-system rehabilitation have been taken. The gradual
      integration of malaria control into routine health-care delivery is planned. This
      process should be guided by the knowledge and experience gained during the
      complex emergency and a focus on malaria should be maintained until the disease
      is brought under control.

PMID- 15850638
TI  - "I think she's just crazy".

PMID- 15850639
TI  - Chest pain and fleeting neurological signs.

PMID- 15850640
TI  - Human placenta: a human organ for developmental toxicology research and
      biomonitoring.
AB  - Pregnant mothers are exposed to a wide variety of foreign chemicals. This
      exposure is most commonly due to maternal medication, lifestyle factors, such as
      smoking, drug abuse, and alcohol consumption, or occupational and environmental
      sources. Foreign compounds may interfere with placental functions at many levels
      e.g. signaling, production and release of hormones and enzymes, transport of
      nutrients and waste products, implantation, cellular growth and maturation, and
      finally, at the terminal phase of placental life, i.e. delivery. Placental
      responses may also be due to pharmaco-/toxicodynamic responses to foreign
      chemicals, e.g. hypoxia. On the other hand, placental xenobiotic-metabolizing
      enzymes can detoxify or activate foreign chemicals, and transporters either
      enhance or prevent cellular accumulation and transfer across the placenta. The
      understanding of what xenobiotics do to the placenta and what the placenta does
      to the xenobiotics should provide the basis for the use of placenta as a tool to
      investigate and predict some aspects of developmental toxicity. This review aims
      to give an update of the fate and behavior of xenobiotics in the placenta from
      the viewpoint of xenobiotic-metabolizing enzymes and transporters. Their response
      levels will be described according to gestational status and methods used. The
      effects of foreign chemicals on placental metabolizing enzymes will be discussed.
      Also, interactions in the transporter protein level will be covered. The role of
      the placenta in contributing to developmental effects and fetotoxicity will be
      examined. The toxicological effects of maternal medications, smoking, and
      environmental exposures (dioxins, pesticides) as well as some possibilities for
      biomonitoring will be highlighted.

PMID- 15850641
TI  - The correlation between sampling site and gene expression in the term human
      placenta.
AB  - Using oligonucleotide microarrays we recently identified a set of transcripts
      that were up-regulated in hypoxic human trophoblasts. To test the hypothesis that
      expression of hypoxia-related placental transcripts depends on sampling site we
      analyzed nine different sites from term human placentas (n=6), obtained after
      uncomplicated pregnancies. These sites spanned the placental center to the
      lateral border and the basal to the chorionic plate. Relative gene expression at
      each site, determined using quantitative PCR, was correlated with villous
      histology. The expression of vascular endothelial growth factor (VEGF) and
      connective tissue growth factor (CTGF), the cytoskeleton proteins lamininA3 and
      alpha-tubulin, and the signal transduction protein Rad was enhanced in the
      subchorionic lateral border compared to medial basal site (1.6-2.9 fold, p<0.05).
      In contrast, the expression of NDRG1, adipophilin and human placental lactogen
      was unchanged. Enhanced villous maturation, syncytial knots and fibrin deposits
      were more frequent in the subchorionic placental lateral border, and correlated
      with up-regulation of hypoxia-related transcripts (p<0.05). The association
      between sample site and expression level was not observed in placentas with
      marginal cord insertion. The expression of hypoxia-related genes in the term
      human placenta is dependent on sampling site within the placental disk, likely
      reflecting local differences in villous perfusion.

PMID- 15850642
TI  - The BeWo choriocarcinoma cell line as a model of iodide transport by placenta.
AB  - Cultured human choriocarcinoma cells of the BeWo line exhibited saturable
      accumulation of radioiodide. Inhibition by competing anions followed the affinity
      series perchlorate >> iodide > or = thiocyanate, consistent with uptake through
      the thyroid iodide transporter, NIS, whose messenger RNA was found in BeWo cells,
      and whose protein was distributed towards the apical pole of the cells. Efflux
      obeyed first order kinetics and was inhibited by DIDS, an antagonist of anion
      exchangers including pendrin, whose messenger RNA was also present. In cultures
      where iodide uptake through NIS was blocked with excess perchlorate, radioiodide
      accumulation was stimulated by exposure to medium in which physiological anions
      were replaced by 2-morpholinoethanesulfonic acid (MES), consistent with the
      operation of an anion exchange mechanism taking up iodide. Chloride in the medium
      was more effective than sulfate at inhibiting this uptake, matching the ionic
      specificity of pendrin. These studies provide evidence that the trophoblast
      accumulates iodide through NIS and releases it to the fetal compartment through
      pendrin.

PMID- 15850643
TI  - Expression of 3beta-hydroxysteroid dehydrogenase type 1, P450 aromatase, and
      17beta-hydroxysteroid dehydrogenase types 1, 2, 5 and 7 mRNAs in human early and
      mid-gestation placentas.
AB  - The placenta is responsible for the production of progesterone (P) and estrogens
      during human pregnancy. In this study, the expression of several key
      steroidogenic enzymes was investigated in different cell types of human placenta
      during early and mid-gestation by in situ hybridization. 3Beta-hydroxysteroid
      dehydrogenase type 1 (3beta-HSD1), P450 aromatase (P450arom) and 17beta
      hydroxysteroid dehydrogenase type 1 (17HSD1) were expressed abundantly in
      syncytiotrophoblast (ST) cells. These three enzymes were also detected in some
      column cytotrophoblast (CCT) cells. 17HSD5 was found in intravillous stromal (IS)
      cells in low levels, suggesting that androgens may be synthesized and metabolized
      in the placenta. 17HSD7 was found in all types of placental cells. Moreover,
      17HSD2 was localized in IS cells. The expression level of 17HSD2 gradually
      increased during pregnancy weeks 7-16, concurrently with the androgen production
      by the male fetus. The present study provides evidence that CCT and IS cells
      participate in P and estrogen biosynthesis, in addition to ST cells. 17HSD2 also
      converts 20alpha-dihydroprogesterone (20-OH-P) to P, whereas 17HSD5 and 17HSD7
      inactivate P. Therefore, the action of 3beta-HSD1 and 17HSD2 on P biosynthesis in
      the placenta is countered by 17HSD5 and 17HSD7, which may provide an optimal
      level of P for the maintenance and progression of pregnancy.

PMID- 15850644
TI  - The cytoplasmic expression of E-cadherin and beta-catenin in bovine trophoblasts
      during binucleate cell differentiation.
AB  - Binucleate cells are endocrine cells generated by the acytokinesis and
      endoreduplication of the trophectoderm in the ruminant placenta. These cells are
      migratory and secrete hormones into the maternal circulation after fusing with
      uterine epithelial cells. In this study, we performed immunohistochemistry for E
      cadherin and beta-catenin in bovine placenta and a bovine trophoblast cell line
      (BT-1). We found that E-cadherin and beta-catenin were distributed not only at
      the cell to cell boundary but throughout the cytoplasm in binucleate cells,
      although they were concentrated at the cell to cell boundary in epithelial cells
      in bovine placenta. Moreover, beta-catenin was detected in the nuclei of
      binucleate cells. Binucleate cells after fusion with uterine epithelial cells
      (feto-maternal hybrid cells) in the maternal side showed no intracellular
      expression of E-cadherin and beta-catenin. The transformation into binucleate
      cells in the BT-1 cell line was also accompanied by the cytoplasmic accumulation
      of E-cadherin and beta-catenin. We further demonstrated that levels of
      cytoplasmic beta-catenin were well correlated with the DNA content of binucleate
      cells in BT-1. The dynamic changes in the distribution of E-cadherin and beta
      catenin suggest an important role in binucleate cells, including the
      rearrangement of cadherin-mediated cell adhesions during cell migration and the
      onset of endoreduplication probably via the nuclear transfer of beta-catenin.

PMID- 15850645
TI  - Increased phospholipase A2 and thromboxane but not prostacyclin production by
      placental trophoblast cells from normal and preeclamptic pregnancies cultured
      under hypoxia condition.
AB  - In this study we determined whether hypoxia could promote vasoactivator
      thromboxane (TX) and prostacyclin (PGI2) as well as phospholipase A2 (PLA2)
      production by placental trophoblast cells (TCs) from normal and preeclamptic (PE)
      pregnancies. Placentas were obtained immediately after delivery from normal (n=9)
      and preeclamptic (n=9) pregnancies. TCs were isolated by dispase digestion of
      villous tissue and purified by Percoll gradient centrifugation. TCs (5x10(6)
      cells/well) were cultured with Dulbecco's Modified Eagles Medium (DMEM) under
      hypoxia condition (2% O2/5% CO2/93% N2) for 48 h. TCs cultured under normoxia
      condition (5% CO2/air) were used as control. Culture medium was collected at the
      end of incubation. Productions for TX, PGI2 and PLA2 were measured by ACE
      competitive enzyme immunoassay (EIA). Comparisons were made using the Mann
      Whitney U test or paired t-test and the data are expressed as mean+/-SE
      (pg/microg cellular protein). Significance was set at a p-value of <0.05. We
      found: (1) PE-TCs produced more TXB2 and PLA2 than normal-TCs under normoxia
      conditions, TXB2: 4.33+/-1.03 vs. 1.84+/-0.29 pg/microg protein, p<0.05; PLA2:
      0.38+/-0.08 vs. 0.21+/-0.03 pg/microg protein, p<0.05, respectively. (2) Hypoxia
      promoted both PE- and normal-TCs to generate more TXB2 and PLA2, TXB2: 6.36+/
      1.72 vs. 3.05+/-0.45 pg/microg; PLA2: 0.52+/-0.10 vs. 0.30+/-0.04 pg/microg,
      respectively. (3) No change in 6-keto PGF1alpha production was observed for
      normal-TCs or PE-TCs when compared under normoxia vs. hypoxia condition, normal
      TCs: 0.20+/-0.05 vs. 0.21+/-0.05 pg/microg; PE-TCs: 0.38+/-0.05 vs. 0.36+/-0.04
      pg/microg, respectively. We concluded that hypoxia promotes both PLA2 and TX, but
      not PGI2, production by placental trophoblast cells cultured under hypoxia
      condition. These results suggest that increased PLA2 release may alter the
      arachidonic acid cascade and promote TX synthesis. Relative hypoxia could
      contribute to the increase in TX production and result in vasoconstriction in
      placental vasculature in preeclampsia.

PMID- 15850646
TI  - Placental dysfunction in Suramin-treated rats--a new model for pre-eclampsia.
AB  - Impaired placentation and oxidative stress are proposed to play major roles in
      the pathogenesis of placental dysfunction and pre-eclampsia. This study was
      carried out to evaluate if inhibited angiogenesis by Suramin injections in early
      pregnancy may cause a condition resembling pre-eclampsia in rats. Rats of two
      different Sprague-Dawley strains, U and H, were given intraperitoneal injections
      of Suramin or saline in early pregnancy. The outcome of pregnancy was evaluated
      on gestational day 20. Suramin injections caused increased blood pressure and
      decreased renal blood flow in the U rats. In both rat strains Suramin decreased
      the placental blood flow and caused fetal growth retardation. In both strains the
      placental concentration of the isoprostane 8-epi-PGF2alpha was increased,
      indicating oxidative stress. The serum concentration of Endothelin-1 was
      increased in the U rats. The U strain had a lower basal placental blood flow, and
      the effects of Suramin were more pronounced in this strain. We conclude, that
      Suramin injections to pregnant rats cause a state of placental insufficiency,
      which partly resembles human pre-eclampsia. The induction of this condition is at
      least partly mediated by oxidative stress, and is subject to varied genetic
      susceptibility.

PMID- 15850647
TI  - Fatal fetal hemorrhage and placental pathology. Report of three cases and a new
      setting.
AB  - We report three cases of late third trimester fetal death in utero consequent to
      fetal exsanguination from the chorionic vasculature. In general, fetal hemorrhage
      is unusual, exsanguination is rare and the location and basis of the hemorrhage
      varies widely. Intragestational and intrapartum hemorrhage is far more often of
      maternal rather than fetal origin. Even when severe, the former is almost always
      manageable whilst the latter may be clinically obscure, intractable, catastrophic
      and fatal. In this presentation, we review and characterize fetal hemorrhage by
      anatomical location and on the basis of its underlying origins. In our first two
      cases, the chorionic vascular failure is understood on the basis of mechanical
      factors, such as tearing by the presenting part or an amniotomy hook. Our third
      case demonstrates the first reported instance in which a severe chorionic
      vasculopathy has damaged a placental surface vessel sufficiently to permit
      spontaneous rupture and fetal exsanguination.

PMID- 15850648
TI  - Feto-feto-fetal transfusion syndrome in monozygotic monochorionic triamniotic
      triplets: vascular evaluation by a cast model.
AB  - A unique cast model of the placenta in a rare case of feto-feto-fetal triplet
      transfusion syndrome (FFFTTS) allowed the demonstration of why the transfusion
      syndrome developed in one fetus and not in the other two in that single placenta.
      The vasculature anatomy of a monochorionic triamniotic triplet placenta with
      FFFTTS of three healthy infants (one donor, two recipients) born in the 35th week
      of gestation was cast by means of dental casting materials. After the cast
      hardened, the tissue was corroded, revealing the cast blood vessels. The
      diameters and lengths of the chorionic blood and intraplacental vessels of the
      cast placenta were measured with a digital caliper. The cast revealed two artery
      artery (A-A) anastomoses on the chorionic plate between the two recipients and
      the donor. Seven artery-vein (A-V) deep anastomoses connected only the arteries
      of the donor and the veins of the two recipients. The blood vessel connections
      among the fetuses allowed the evaluation of a pathologic case with its own
      control in a single placenta. From the vascular appearance, we speculate that the
      A-A anastomoses between the two fetuses protected them from developing blood
      transfusions, but that the A-V anastomoses contributed to their development.

PMID- 15850649
TI  - Feto-feto-fetal transfusion syndrome in monozygotic monochorionic triamniotic
      triplets: vascular evaluation by a cast model.

PMID- 15850651
TI  - Introduction.

PMID- 15850652
TI  - Physiology of microglial cells.
AB  - Microglial cells in culture and in situ express a defined pattern of K(+)
      channels, which is distinct from that of other glial cells and neurons. This
      pattern undergoes defined changes with microglial activation. As expected for a
      cell with immunological properties, microglia express a variety of cytokine and
      chemokine receptors, which are linked to the mobilization of Ca(2+) (cytosolic
      free calcium) from internal stores. Microglial cells also have the capacity to
      respond to neuronal activity: they express receptors for the major excitatory
      receptor glutamate and the main inhibitory receptor GABA (gamma-amino butyric
      acid). By expressing purinergic receptors, microglia can sense astrocyte activity
      in the form of Ca(2+) waves. Activation of transmitter receptors can affect
      cytokine release which is a potential means as to how brain activity can affect
      immune function.

PMID- 15850653
TI  - Pathophysiological roles of extracellular nucleotides in glial cells:
      differential expression of purinergic receptors in resting and activated
      microglia.
AB  - Microglial cells are the major cellular elements with immune function inside the
      CNS and play important roles in orchestrating inflammatory brain response to
      hypoxia and trauma. Although a complete knowledge of the endogenous factors
      leading to a prompt activation of microglia is not yet available, activation of
      P2 purinoreceptors by extracellular ATP has been indicated as a primary factor in
      microglial response. A still unresolved question, however, is which subtype(s) of
      P2 receptors mediate(s) the response to ATP. By a combination of RT-PCR, Western
      blotting, and single-cell calcium imaging, we assessed the presence and the
      activity of P2 receptor subtypes in the mouse microglial cell line N9. All
      members of the P2 receptor family, including the recently reported receptor for
      sugar nucleotides (P2Y(14)), were found to be present in these cells at mRNA
      and/or protein level. The functionality of the receptors was assessed by analysis
      of the calcium responses evoked by specific agonists both in N9 cells and in
      primary microglia from rat brain. Interestingly, a different functional profile
      of P2 receptors was observed in resting or in LPS-activated N9 cells. Overnight
      exposure to LPS increased P2Y(6) and P2Y(14), decreased P2X(7), and left
      unchanged P2Y(1) and P2Y(2,4) receptor activity. The change in the P2 receptor
      profile in activated cells suggests selective roles for specific P2 receptor
      subtypes in microglial activation triggered by LPS. We speculate that modulation
      of microglial cell function via subtype-selective P2 receptor ligands may open up
      new strategies in the therapeutic management of inflammatory neurological
      diseases characterized by abnormal microglia response.

PMID- 15850654
TI  - ATP regulates oligodendrocyte progenitor migration, proliferation, and
      differentiation: involvement of metabotropic P2 receptors.
AB  - Extracellular nucleotides act as potent signaling molecules in the neuron-glia
      and glia-glia communication, via the activation of specific ligand-gated P2X and
      G-protein-coupled metabotropic P2Y receptors. Most of the data available about
      the effects of P2 receptor activation in the CNS concern astrocytes, microglia,
      and neurons. To gain insights into the role of purinergic receptors in
      oligodendrocyte development, we characterized the expression and functional
      activity of P2 receptors in rat oligodendrocyte progenitors (OPs) and
      investigated the effects of ATP and its breakdown products on their functions. We
      describe here that rat OPs express different types of P2 receptors and that
      nucleotide-induced Ca(2+) raises in these progenitor cells are mainly due to the
      activation of P2X(7) ionotropic and ADP-sensitive P2Y(1) metabotropic receptors.
      We also show that ATP and ADP stimulate OP migration, inhibit the mitogenic
      response of OPs to PDGF and promote oligodendrocyte differentiation. The
      pharmacological profile of the nucleotide-induced effects demonstrates the
      important regulatory role of P2Y(1) receptor signaling in OP functions. These
      findings suggest that ATP, which is released in high amounts under inflammatory
      conditions and following cell death, might regulate remyelination processes in
      inflammatory demyelinating diseases of the CNS, like multiple sclerosis.

PMID- 15850655
TI  - Cytokine-mediated inflammation, tumorigenesis, and disease-associated
      JAK/STAT/SOCS signaling circuits in the CNS.
AB  - Cytokines are plurifunctional mediators of cellular communication. The CNS
      biology of this family of molecules has been explored by transgenic approaches
      that targeted the expression of individual cytokine genes to specific cells in
      the CNS of mice. Such transgenic animals exhibit wide-ranging structural and
      functional alterations that are linked to the development of distinct
      neuroinflammatory responses and gene expression profiles specific for each
      cytokine. The unique actions of individual cytokines result from the activation
      of specific receptor-coupled cellular signal transduction pathways such as the
      JAK/STAT tyrosine kinase signaling cascade. The cerebral expression of various
      STATs, their activation, as well as that of the major physiological inhibitors of
      this pathway, SOCS1 and SOCS3, is highly regulated in a stimulus- and cell
      specific fashion. The role of the key IFN signaling molecules STAT1 or STAT2 was
      studied in transgenic mice (termed GIFN) with astrocyte-production of IFN-alpha
      that were null or haploinsufficient for these STAT genes. Surprisingly, these
      animals developed either more severe and accelerated neurodegeneration with
      calcification and inflammation (GIFN/STAT1 deficient) or severe
      immunoinflammation and medulloblastoma (GIFN/STAT2 deficient). STAT dysregulation
      may result in a signal switch phenomenon in which one cytokine acquires the
      apparent function of an entirely different cytokine. Therefore, for cytokines
      such as the IFNs, the receptor-coupled signaling process is complex, involving
      the coexistence of multiple JAK/STAT as well as alternative pathways. The
      cellular compartmentalization and balance in the activity of these pathways
      ultimately determines the repertoire and nature of CNS cytokine actions.

PMID- 15850656
TI  - Cytokine and chemokine inter-regulation in the inflamed or injured CNS.
AB  - The distinction between immune-regulatory and effector cytokines and chemokines,
      and neural growth and survival factors (neurotrophins) becomes increasingly
      blurred. We discuss here the role of immune cytokines and chemokines as mediators
      of innate glial responses in the central nervous system. Glial responses to
      axonal degeneration in the hippocampus dentate gyrus are initiated independently
      of immune involvement, following transection of afferent entorhinal (perforant
      path) axons. The glial responses that we measure involve early microglial and
      somewhat later astrocyte activations. Among the earliest responses are the
      expression of a wide profile of chemokines, and of the cytokine tumor necrosis
      factor-alpha (TNFalpha). The cytokine interferon-gamma (IFNgamma) is not normally
      produced in the CNS, but TNFalpha levels are enhanced if it is present. Viral
      vector-derived IFNgamma directly induces the expression of chemokines in the CNS,
      in the absence of any other inflammatory event, but the profiles differ from
      those induced by axotomy. Chemokines that bind the CCR2 receptor are implicated
      in traffic of macrophages and T cells to the denervated hippocampus. Innate
      responses in the immune system are directed by Toll-like receptors (TLR). Our
      recent studies focus on specific TLR signals as upstream on-switches for glial
      cytokine and chemokine responses. The biological activity of chemokines is
      regulated by matrix metalloproteinase enzymes (MMPs) and specific members of this
      family are expressed in response to axonal lesioning. These findings strengthen
      the case for the sharing of signals between the immune and nervous system.

PMID- 15850657
TI  - Macrophages and neurodegeneration.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      central nervous system (CNS). Demyelination is a classical feature of MS lesions,
      and neurological deficits are often ascribed to the reduced signal conduction by
      demyelinated axons. However, recent studies emphasize that axonal loss is an
      important factor in MS pathogenesis and disease progression. Axonal loss is found
      in association with cellular infiltrates in MS lesions. In this review, we
      discuss the possible contribution of the innate immune system in this process. In
      particular, we describe how infiltrated macrophages may contribute to axonal loss
      in MS and in experimental autoimmune encephalomyelitis (EAE), the animal model
      for MS. An overview is given of the possible effects of mediators, which are
      produced by activated macrophages, such as such as pro-inflammatory cytokines,
      free radicals, glutamate and metalloproteases, on axonal integrity. We conclude
      that infiltrated macrophages, which are activated to produce pro-inflammatory
      mediators, may be interesting targets for therapeutic approaches aimed to prevent
      or reduce axonal loss during exacerbation of inflammation. Interference with the
      process of infiltration and migration of monocytes across the blood-brain barrier
      is one of the possibilities to reduce the damage by activated macrophages.

PMID- 15850658
TI  - Microglial cell population dynamics in the injured adult central nervous system.
AB  - Reactive microgliosis is characteristic of trauma and stroke as well as
      inflammatory and chronic neurodegenerative disease. A conspicuous feature of the
      microglial reaction to acute neural injury is a massive expansion of the
      microglial cell population which peaks a few days following injury. New data
      based on the use of radiation bone marrow-chimeric mice suggest this expansion
      also involves recruitment of bone marrow-derived cells, which migrate into the
      neural parenchyma and differentiate into microglia. Here, we discuss the
      contribution of bone marrow-derived cells to the injury-induced expansion of the
      microglial cell population, seen in the dentate gyrus with ongoing anterograde
      axonal and terminal synaptic degeneration, subsequent to transection of the
      entorhino-dentate perforant path projection. In this paradigm of minor brain
      injury, the bone marrow-derived cells are grossly outnumbered by activated
      resident microglia, which express the stem cell antigen CD34 concurrent to a
      marked capacity for self-renewal. The observation of a mixed origin of lesion
      reactive microglia, consisting of a smaller subpopulation of exogenous bone
      marrow-derived microglia, and a larger population of activated resident
      microglia, the majority of which express CD34 and undergo proliferation, suggests
      that lesion-reactive microglia consist of functionally distinct cell populations.
      The demonstration of an injury-enhanced recruitment of bone marrow-derived cells
      into the perforant path-denervated dentate gyrus, raises the possibility of using
      genetically manipulated cells as vectors for lesion-site-specific gene therapy
      even in minimally injured areas of the central nervous system.

PMID- 15850659
TI  - Ligands for peripheral benzodiazepine binding sites in glial cells.
AB  - Within the diseased brain, glial cells and in particular, microglia, express a
      multimeric protein complex termed "peripheral benzodiazepine binding sites
      (PBBS)" or "peripheral benzodiazepine receptor (PBR)". The expression of the PBBS
      is dependent on the functional state of the cell and in glial cells is triggered
      by a wide range of activating stimuli. In the healthy brain, the PBBS are nearly
      absent with the notable exception of the choroid plexus, ependymal layer,
      perivascular cells, central canal, possibly certain nuclei in the brainstem and
      layers in the cerebellum where a constitutive presence of the PBBS is found.
      Likewise, areas that due to the absence of the blood-brain barrier contain more
      active glial cells, such as the pituitary gland, or the area postrema at floor of
      the 4th ventricle show a degree of constitutive expression. The tight correlation
      of the parenchymal de novo expression of the PBBS with the presence of activated
      glial cells, that in turn are usually only found in tissue affected by
      progressive disease, establishes the PBBS as a generic marker for the detection
      and measurement of active disease processes in the brain. Specific radioligands
      of the PBBS for use in positron emission tomography (PET) may thus provide a
      sensitive in vivo index of neuropathological activity. Whilst prototype ligands
      for the PBBS are available, future research needs to focus on the development of
      new ligands with improved pharmacodynamic properties and the ability to
      discriminate between the different, still insufficiently understood functional
      states of the peripheral benzodiazepine receptor complex.

PMID- 15850660
TI  - Neural stem cells and their use as therapeutic tool in neurological disorders.
AB  - Spontaneous neural tissue repair occurs in patients affected by inflammatory and
      degenerative disorders of the central nervous system (CNS). However, this process
      is not robust enough to promote a functional and stable recovery of the CNS
      architecture. The development of cell-based therapies aimed at promoting brain
      repair, through damaged cell-replacement, is therefore foreseen. Several
      experimental cell-based strategies aimed at replacing damaged neural cells have
      been developed in the last 30 years. Although successful in promoting site
      specific repair in focal CNS disorders, most of these therapeutic approaches have
      failed to foster repair in multifocal CNS diseases where the anatomical and
      functional damage is widespread. Stem cell-based therapies have been recently
      proposed and might represent in the near future a plausible alternative strategy
      in these disorders. However, before envisaging any human applications of stem
      cell-based therapies in neurological diseases, we need to consider some
      preliminary and still unsolved issues: (i) the ideal stem cell source for
      transplantation, (ii) the most appropriate route of stem cell administration,
      and, last but not least, (iii) the best approach to achieve an appropriate,
      functional, and long-lasting integration of transplanted stem cells into the host
      tissue.

PMID- 15850661
TI  - Innate (inherent) control of brain infection, brain inflammation and brain
      repair: the role of microglia, astrocytes, "protective" glial stem cells and
      stromal ependymal cells.
AB  - In invertebrates and primitive vertebrates, the brain contains large numbers of
      "professional" macrophages associated with neurones, ependymal tanycytes and
      radial glia to promote robust regenerative capacity. In higher vertebrates,
      hematogenous cells are largely excluded from the brain, and innate immune
      molecules and receptors produced by the resident "amateur" macrophages
      (microglia, astrocytes and ependymal cells) control pathogen infiltration and
      clearance of toxic cell debris. However, there is minimal capacity for
      regeneration. The transfer of function from hematogenous cells to macroglia and
      microglia is associated with the sophistication of a yet poorly-characterized
      neurone-glia network. This evolutionary pattern may have been necessary to reduce
      the risk of autoimmune attack while preserving the neuronal web but the ability
      to repair central nervous system damage may have been sacrificed in the process.
      We herein argue that it may be possible to re-educate and stimulate the resident
      phagocytes to promote clearance of pathogens (e.g., Prion), toxic cell debris
      (e.g., amyloid fibrils and myelin) and apoptotic cells. Moreover, as part of this
      greater division of labour between cell types in vertebrate brains, it may be
      possible to harness the newly described properties of glial stem cells in
      neuronal protection (revitalization) rather than replacement, and to control
      brain inflammation. We will also highlight the emerging roles of stromal
      ependymal cells in controlling stem cell production and migration into areas of
      brain damage. Understanding the mechanisms involved in the nurturing of damaged
      neurons by protective glial stem cells with the safe clearance of cell debris
      could lead to remedial strategies for chronic brain diseases.

PMID- 15850662
TI  - Microglia and neuroprotection: implications for Alzheimer's disease.
AB  - The first part of this paper summarizes some of the key observations from
      experimental work in animals that support a role of microglia as neuroprotective
      cells after acute neuronal injury. These studies point towards an important role
      of neuronal-microglial crosstalk in the facilitation of neuroprotection.
      Conceptually, injured neurons are thought to generate rescue signals that trigger
      microglial activation and, in turn, activated microglia produce trophic or other
      factors that help damaged neurons recover from injury. Against this background,
      the second part of this paper summarizes recent work from postmortem studies
      conducted in humans that have revealed the occurrence of senescent, or
      dystrophic, microglial cells in the aged and Alzheimer's disease brain. These
      findings suggest that microglial cells become increasingly dysfunctional with
      advancing age and that a loss of microglial cell function may involve a loss of
      neuroprotective properties that could contribute to the development of aging
      related neurodegeneration.

PMID- 15850663
TI  - Interactions between Alzheimer's disease and cerebral ischemia--focus on
      inflammation.
AB  - Progressive memory impairment, beta-amyloid (Abeta) plaques associated with local
      inflammation, neurofibrillary tangles, and loss of neurons in selective brain
      areas are hallmarks of Alzheimer's disease (AD). Although beta-amyloid precursor
      protein (APP) and Abeta have a central role in the etiology of AD, it is not
      clear which forms of APP or Abeta are responsible for the neuronal vulnerability
      in AD brain. Brain ischemia, another cause of dementia in the elderly, has
      recently been recognized to contribute to the pathogenesis of AD and individuals
      with severe cognitive decline and possibly underlying AD are at increased risk
      for ischemic events in the brain. Moreover, the epsilon4 allele of apolipoprotein
      E (ApoE) is a risk factor for both AD and poor outcome following brain ischemia
      and hemorrhage. Several factors and molecular mechanisms that lower the threshold
      of neuronal death in models of AD have recently been described. Among these
      neuroinflammation seems to play an important role. The development and maturation
      of both AD neuropathology and ischemic lesions in the central nervous system are
      characterized by activation of glial cells and upregulation of inflammatory
      mediators. Indeed, anti-inflammatory approaches have proven to be beneficial in
      the prevention and treatment of AD-like neuropathology and ischemic injuries in
      vivo. This review summarizes some of the findings suggesting that neuronal
      overexpression of human APP renders the brain more vulnerable to ischemic injury
      and describes the factors that are involved in increased neuronal susceptibility
      to ischemic stroke.

PMID- 15850664
TI  - Microglial activation in chronic neurodegenerative diseases: roles of apoptotic
      neurons and chronic stimulation.
AB  - In chronic neurodegenerative diseases, microglial activation is an early sign
      that often precedes neuronal death. Increasing evidence indicates that in these
      chronic pathologies activated microglia sustain a local inflammatory response.
      Nonetheless, the potential detrimental or protective roles of such reaction
      remain to date not fully understood, mainly because of the lack of direct
      evidence of the functional properties acquired by microglia in the course of
      chronic diseases. Purified microglial cultures have been extensively used to
      investigate microglial functions associated with activation, but they are often
      criticized for some experimental constrains, including the abrupt addition of
      activators, the limited time of stimulation, and the absence of interactions with
      neurons or other elements of brain parenchyma. To limit these confounding
      factors, we developed in vitro models in which microglial cells were repeatedly
      challenged with lipopolysaccharide or co-cultured with healthy, apoptotic, or
      necrotic neuronal cells. We found that chronic stimulation and interaction with
      phosphatidylserine-expressing apoptotic cells induced microglial cells to release
      immunoregulatory and neuroprotective agents (prostaglandin E(2), transforming
      growth factor-beta, and nerve growth factor), whereas the synthesis of pro
      inflammatory molecules (tumor necrosis factor-alpha and nitric oxide) was
      inhibited. These findings suggest that signals that are relevant to chronic
      diseases lead to a progressive down-regulation of pro-inflammatory microglial
      functions and may help in understanding the atypical microglial activation that
      begins to be recognized in some chronic neuropathologies.

PMID- 15850665
TI  - The amyloid precursor protein and its network of interacting proteins:
      physiological and pathological implications.
AB  - The amyloid precursor protein (APP) is an ubiquitous receptor-like molecule
      involved in the pathogenesis of Alzheimer's disease that generates beta-amyloid
      peptides and causes plaque formation. APP and some of its C-terminal proteolytic
      fragments (CTFs) have also been shown to be in the center of a complex protein
      protein network, where selective phosphorylation of APP C-terminus may regulate
      the interaction with cytosolic phosphotyrosine binding (PTB) domain or Src
      homology 2 (SH2) domain containing proteins involved in cell signaling. We have
      recently described an interaction between tyrosine-phosphorylated CTFs and ShcA
      adaptor protein which is highly enhanced in AD brain, and a new interaction
      between APP and the adaptor protein Grb2 both in human brain and in neuroblastoma
      cultured cells. These data suggest a possible role in cell signaling for APP and
      its CTFs, in a manner similar to that previously reported for other receptors,
      through a tightly regulated coupling with intracellular adaptors to control the
      signaling of the cell. In this review, we discuss the significance of these novel
      findings for AD development.

PMID- 15850666
TI  - Molecular and cellular insights into the coxsackie-adenovirus receptor: role in
      cellular interactions in the stem cell niche.
AB  - In recent years, progress has been made in characterizing the molecular and
      cellular elements that are responsible for the regeneration in the damaged brain
      and highlighting the key role of the stromal-vascular 'environment' to
      orchestrate secondary neurogenesis and repair. Indeed, the ability of the stem
      cells to self-renew and differentiate is tightly regulated by stromal ependymal
      cells and endothelial cells expressing molecular cues that constitute the
      extracellular stem cell 'niche'. Several soluble growth factors such as EGF,
      TGFbeta, FGF2, SDF-1alpha and Noggin are important signals for the stem cell
      niche but little is known about the role of membrane-bound molecules in
      intercellular communications between the niche and the stem cells. In this mini
      review, we highlight the emerging role of a family of adhesion molecules in the
      control of secondary neurogenesis. The coxsackie-adenovirus receptor (CAR) is a
      46 kDa transmembrane protein and a member of the immunoglobulin super family. It
      is close structurally and evolutionary to other adhesion molecules involved in
      cell-cell interactions during embryogenesis, broadly expressed in the developing
      central nervous system but restricted to ependymal cells in the adult brain. This
      unique location and its newly established signalling properties further support
      the role of CAR in intercellular communications. Elucidating the other signalling
      molecules and manipulating the stromal-vascular niche for example by adenovirus
      gene therapy remain important goals for future clinical applications.

PMID- 15850667
TI  - Glia-neuron crosstalk in the neuroprotective mechanisms of sex steroid hormones.
AB  - Proteins involved in the intramitochondrial trafficking of cholesterol, the first
      step in steroidogenesis, such as the steroidogenic acute regulatory protein
      (StAR) and the peripheral-type benzodiazepine receptor (PBR), are upregulated in
      the nervous system after injury. Accordingly, a local increase in the levels of
      steroids, such as pregnenolone and progesterone, is observed following traumatic
      injury in the brain and spinal cord. The expression and activity of aromatase,
      the enzyme that synthesizes estradiol, is also increased in injured brain areas
      and its inhibition results in an increased neurodegeneration. These findings
      suggest that an increase in steroidogenesis is part of an overall mechanism used
      by the nervous tissue to cope with neurodegenerative conditions. Neural
      steroidogenesis is the result of a coordinated interaction of neurons and glia.
      For example, after neural injury, there is an upregulation of StAR in neurons and
      of PBR in microglia and astroglia. Aromatase is expressed in neurons under basal
      conditions and is upregulated in reactive astrocytes after injury. Some of the
      steroids produced by glia are neuroprotective. Progesterone and progesterone
      derivatives produced by Schwann cells, promote myelin formation and the
      remyelination and regeneration of injured nerves. In the central nervous system,
      the steroids produced by glia regulate synaptic function, affect anxiety,
      cognition, sleep and behavior, and exert neuroprotective and reparative roles. In
      addition, glial cells are targets for steroids and mediate some of the effects of
      these molecules on neurons, including the regulation of survival and
      regeneration.

PMID- 15850668
TI  - Glucocorticoid regulation of glial responses during hippocampal neurodegeneration
      and regeneration.
AB  - Glucocorticoids can prevent or accelerate neurodegeneration in the adult rat
      hippocampus. To investigate these actions of glucocorticoids, we previously
      cloned genes from the hippocampus. Adrenalectomy specifically increased glial
      fibrillary acidic protein and transforming growth factor (TGF)-beta1 mRNAs in the
      dentate gyrus and these effects were dependent on induced apoptosis.
      Corticosterone treatment prevented apoptosis, and decreased glial activation and
      the influx of activated microglia. Since these effects are opposite to injury and
      neurodegeneration, we propose that they represent adaptive actions of
      glucocorticoids, preventing cellular defense mechanisms from overshooting. We
      used adrenalectomy as a model to investigate how adult granule neurons die in
      vivo and the effects of neurotrophic factors in protecting against apoptosis.
      Neurotrophin-4/5 and TGF-beta1 protected granule neurons against adrenalectomy
      induced apoptosis. Since neurogenesis is also greatly increased in the dentate
      gyrus following adrenalectomy, we compared the time course of birth and death
      with glial responses. TGF-beta1 mRNA increased before the detection of dying
      cells in the dentate gyrus, which was coincident with increased proliferation in
      the neurogenic zone. Glucocorticoids also increased Ndrg2 mRNA in glia in the
      neurogenic zone; Ndrg2 is a member of a novel gene family involved in neural
      differentiation and synapse formation. Therefore, studying the effects of
      glucocorticoid manipulation on the dentate gyrus is increasing our understanding
      of how mature neurons die by apoptosis and the role of glia in induced apoptosis
      and neurogenesis. Discovering how endocrine and inflammatory responses regulate
      neuron birth and survival is important for developing successful neuron
      replacement strategies to treat neurodegenerative diseases.

PMID- 15850669
TI  - Glucocorticoid receptor-nitric oxide crosstalk and vulnerability to experimental
      parkinsonism: pivotal role for glia-neuron interactions.
AB  - Inflammation and oxidative stress have been closely associated with the
      pathogenesis of neurodegenerative disorders, including Parkinson's disease (PD).
      The expression of inducible nitric oxide synthase (iNOS) in astrocytes and
      microglia and the production of large amounts of nitric oxide (NO) are thought to
      contribute to dopaminergic neuron demise. Increasing evidence, however, indicates
      that activated astroglial cells play key roles in neuroprotection and can promote
      recovery of CNS functions. Endogenous glucocorticoids (GCs) via glucocorticoid
      receptors (GRs) exert potent anti-inflammatory and immunosuppressive effects and
      are key players in protecting the brain against stimulation of innate immunity.
      Here we review our work showing that exposure to a dysfunctional GR from early
      embryonic life in transgenic (Tg) mice expressing GR antisense RNA represents a
      key vulnerability factor in the response of nigrostriatal dopaminergic neurons to
      the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and further
      report that exacerbation of dopaminergic neurotoxicity with no recovery is
      determined by failure of astroglia to exert neuroprotective effects. Aberrant
      iNOS gene expression and increased glia vulnerability to cell death characterized
      the response of GR-deficient mice to stimulation of innate immunity. More
      importantly, GR-deficient glial cells failed to protect fetal dopaminergic
      neurons against oxidative stress-induces cell death, whereas wild-type glia
      afforded neuroprotection. Thus, lack of iNOS/NO regulation by GCs can program an
      aberrant GR-NO crosstalk in turn responsible for loss of astroglia
      neuroprotective function in response to stimulation of innate immunity, pointing
      to glia and efficient GR-NO dialogue as pivotal factors orchestrating
      neuroprotection in experimental parkinsonism.

PMID- 15850671
TI  - Peripheral nerves: a target for the action of neuroactive steroids.
AB  - Peripheral nervous system possesses both classical and non-classical steroid
      receptors and consequently may represent a target for the action of neuroactive
      steroids. The present review summarizes the state of art of this intriguing field
      of research reporting data which indicate that neuroactive steroids, like for
      instance progesterone, dihydroprogesterone, tetrahydroprogesterone,
      dihydrotestosterone and 3alpha-diol, stimulate the expression of two important
      proteins of the myelin of peripheral nerves, the glycoprotein P0 (P0) and the
      peripheral myelin protein 22 (PMP22). Interestingly, the mechanisms by which
      neuroactive steroids exert their effects involve classical steroid receptors,
      like for instance progesterone and androgen receptors, in case of P0 and non
      classical steroid receptors, like GABA(A) receptor, in case of PMP22. Moreover,
      neuroactive steroids not only control the expression of these specific myelin
      proteins, but also influence the morphology of myelin sheaths and axons
      suggesting that these molecules may represent an interesting new therapeutic
      approach to maintain peripheral nerve integrity during neurodegenerative events.

PMID- 15850670
TI  - Hormone regulation of microglial cell activation: relevance to multiple
      sclerosis.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      hormone receptor superfamily of proteins. The role of PPARs in regulating the
      transcription of genes involved in glucose and lipid metabolism has been
      extensively characterized. Interestingly, PPARs have also been demonstrated to
      mediate inflammatory responses. Microglia participate in pathology associated
      with multiple sclerosis (MS). Upon activation, microglia produce molecules
      including NO and TNF-alpha that can be toxic to CNS cells including myelin
      producing oligodendrocytes and neurons, which are compromised in the course of
      MS. Previously, we and others demonstrated that PPAR-gamma agonists including 15d
      PGJ(2) are effective in the treatment of experimental autoimmune
      encephalomyelitis (EAE), an animal model of MS. PPAR-gamma modulation of EAE may
      occur, at least in part, by inhibition of microglial cell activation. Here, we
      indicate that 15d-PGJ(2) is a more potent inhibitor of microglial activation than
      thiazolidinediones, which are currently used to treat diabetes. Furthermore, 15d
      PGJ(2) acts cooperatively with 9-cis retinoic acid, the ligand for the retinoid X
      receptor (RXR), in inhibiting microglial cell activation. This suggests that 15d
      PGJ(2) and 9-cis RA inhibit cell activation through the formation of PPAR
      gamma/RXR heterodimers. Interestingly, PGA(2), which like 15d-PGJ(2) is a
      cyclopentenone prostaglandin, but which unlike 15d-PGJ(2) does not bind PPAR
      gamma, is a potent inhibitor of microglial cell activation. Collectively, these
      studies suggest that 15d-PGJ(2) inhibits microglial cell activation by PPAR-gamma
      dependent as well as PPAR-gamma-independent mechanisms. The studies further
      suggest that the PPAR-gamma agonist 15d-PGJ(2) in combination with retinoids may
      be effective in the treatment of MS.

PMID- 15850672
TI  - Thyroid hormone and remyelination in adult central nervous system: a lesson from
      an inflammatory-demyelinating disease.
AB  - Re-myelination in the adult CNS has been demonstrated in different experimental
      models of demyelinating diseases. However, there is no clear evidence that re
      myelination is effective in multiple sclerosis (MS), the most diffuse
      demyelinating disease. Moreover, chronic disabilities in MS are believed to be
      due to remyelination failure and consequent neuron damage and degeneration. Due
      to the presence of numerous oligodendrocyte precursors inside demyelination
      plaques, reasons for remyelination failure are unknown. In this paper, we
      reviewed data from embryonic development and in vitro studies supporting the
      primary role of thyroid hormone in oligodendrocyte maturation. We also reviewed
      personal data on the possibility of promoting myelination in chronic experimental
      allergic encephalomyelitis (EAE), a widely used experimental model of MS, by
      recruiting progenitors and channeling them into oligodendroglial lineage through
      the administration of thyroid hormone.

PMID- 15850673
TI  - Preservation of DNA integrity and neuronal degeneration.
AB  - The mismatch repair system (MMR) is an important member of the DNA checkpoint,
      that includes a number of protein deputed to control genomic stability through
      cell cycle arrest, DNA repair, and apoptosis. Here we summarize some recent data
      from our and other groups underlining the contribution to neurodegeneration of
      MSH2, perhaps the most relevant component of the MMR system. These data suggest
      that this protein participates not only in the cancer prevention machinery for
      the body but also in neurodegenerative processes.

PMID- 15850674
TI  - New insights into COX-2 biology and inhibition.
AB  - It is now established that prostanoids play important roles in many cellular
      responses and pathophysiologic processes including modulation of the inflammatory
      reaction, erosion of cartilage and juxtaarticular bone, gastrointestinal
      cytoprotection and ulceration, angiogenesis and cancer, hemostasis and
      thrombosis, renal hemodynamics, and progression of kidney disease. The initial
      step in the formation of prostanoids, i.e., the conversion of free arachidonic
      acid (AA) to prostaglandin (PG)G(2) and then to PGH(2), is controlled by two PGH
      synthases (COX-1 and COX-2). Selective inhibitors of COX-2 (coxibs) have
      established efficacy in the treatment of pain and inflammation comparable to that
      of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) but exhibit
      enhanced gastrointestinal safety. Several lines of evidence suggest a critical
      role of COX-2 expression in cancer and selective COX-2 inhibitors may represent
      novel chemopreventive tools. Moreover, it has been suggested that COX-2
      inhibitors may contribute to maintain high levels of chemotherapeutics in tumor
      tissues by preventing the overexpression of the multidrug resistance protein
      MDR1/P-gp. The place of COX-2 inhibitors in neurological diseases continues to
      attract basic and clinical investigation. The possible involvement of COX-2 in
      neurodegeneration, substained by the results of epidemiological studies with
      nonselective NSAIDs, has not been confirmed by the results of initial clinical
      trials with coxibs in Alzheimer's disease. Recently, the involvement of COX-2 in
      endogenous cannabinoid system has been suggested. Interestingly, COX-2-mediated
      oxygenation of arachidonylethanolamide (anandamide, AEA) and 2
      arachidonylglycerol (2-AG) provides diverse sets of novel lipids that are
      structurally related to prostaglandins.

PMID- 15850675
TI  - From proteomics to biomarker discovery in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia in the elderly. AD
      is an invariably fatal neurodegenerative disorder with no effective treatment or
      definitive antemortem diagnostic test. Little is known about the changes in the
      brain preceding or accompanying initiation of the disease. Understanding the
      biological processes, which occur during AD onset and/or progression, will
      improve the diagnosis and treatment of the disease. As we will discuss in this
      review article, using high-throughput cDNA microarray we identified candidate
      genes whose expression is altered in the brain of cases at risk for AD dementia.
      However, it is possible that the use of the cDNA microarray technology alone may
      underestimate post-transcriptional modifications and therefore provides only a
      partial view of the biological problem of interest. As such, the combination of
      cDNA and protein arrays may provide a more global picture of the biological
      processes being studied. Based on this hypothesis, we initiated a series of high
      throughput proteomic studies and found that the expressions of proteins involved
      in synaptic plasticity are selectively altered in the brain of cases at high risk
      to develop AD dementia (mild cognitive impairment; MCI). This is consistent with
      our cDNA microarray evidence showing that the expression of a-type synapsins is
      selectively altered in the brain of MCI cases. Collectively, these studies
      support the feasibility and usefulness of high-throughput cDNA microarray and
      proteomics techniques to study the sequential changes of distinctive gene
      expression patterns in the brain as a function of the progression of AD dementia.

PMID- 15850676
TI  - Transgenic AD model mice, effects of potential anti-AD treatments on inflammation
      and pathology.
AB  - The extracellular deposition of amyloid (A) peptides in plaques, and
      neurofibrillary tangles are the two characteristic pathological features of
      Alzheimer's disease (AD). Plaques are surrounded by activated astrocytes and
      microglia, to study the relation between amyloid neuropathology and inflammation,
      we examined the changes in amyloid pathology in the hippocampus following three
      different treatments aimed at reducing the amyloid burden. (1) To investigate the
      effects of long-term cholinergic deafferentation, we lesioned the fimbria-fornix
      pathway in our AD-model mice at 7 months of age, and 11 months post-lesion the
      mice were sacrificed for histopathological analysis. The fimbria-fornix
      transection resulted in a substantial depletion of cholinergic markers in the
      hippocampus, but the lesion did not result in an alteration in hippocampal A
      deposition and inflammation (i.e., numbers or staining density of astrocytes and
      microglia). (2) To investigate the effects of estrogen, we ovariectomized mice
      and treated them with estrogen (sham-lesion, zero dose, low dose, and high dose)
      and studied the pathology at different postsurgery intervals. Estrogen depletion
      (i.e., ovariectomy) or estrogen replacement did not affect A deposition or
      inflammation at any time point. (3) In the final studies, we treated mice with
      flurbiprofen and an NO-donating derivative of flurbiprofen (HCT 1026) for several
      months (from 6 till 14 months of age), and studied the A pathology and
      inflammation in the brain. Sham treatment, flurbiprofen, and the low-dose HCT
      1026 did not affect pathology; however, a higher dose of HCT 1026 reduced both A
      load and amount of microglial activation surrounding plaques.

PMID- 15850677
TI  - Mechanism of neuroprotective action of the anti-Parkinson drug rasagiline and its
      derivatives.
AB  - The mitochondria are directly involved in cell survival and death. Drugs that
      protect mitochondria viability and prevent apoptotic cascade mechanisms involved
      in mitochondrial permeability transition pore (MPTp) will be cytoprotective.
      Rasagiline (N-propargyl-1R-aminoindan) is a novel, highly potent irreversible
      monoamine oxidase (MAO) B inhibitor, anti-Parkinson drug. Unlike selegiline,
      rasagiline is not derived from amphetamine, is not metabolized to neurotoxic l
      methamphetamine derivative, nor does it have sympathomimetic activity. Rasagiline
      is effective as monotherapy or adjunct to L-dopa for patients with early and late
      Parkinson's disease (PD), and adverse events do not occur with greater frequency
      in subjects receiving rasagiline than those on placebo. Controlled studies
      indicate that it might have a disease-modifying effect in PD that may be related
      to neuroprotection. Its S-isomer, TVP1022, is a relatively inactive MAO
      inhibitor. However, both drugs have similar neuroprotective activities in
      neuronal cell cultures in response to various neurotoxins and in vivo (global
      ischemia, neurotrauma, head injury, anoxia, etc.), indicating that MAO inhibition
      is not a pre-requisite for neuroprotection. Structure activity studies have shown
      that the neuroprotective activity is associated with the propargyl moiety of
      rasagiline which protects mitochondrial viability and MPTp by activating Bcl-2
      and protein kinase C (PKC), and down regulating pro-apoptotic FAS and Bax.
      Rasagiline and its derivatives also process amyloid precursor protein (APP) to
      the neuroprotective-neurotrophic soluble APP alpha (sAPPalpha) by PKC and MAP
      kinase-dependent activation of alpha-secretase. The neuroprotective activity of
      propargylamine has led us to develop novel bifunctional neuroprotective iron
      chelating MAO-inhibiting drugs possessing propargyl moiety for the treatment of
      other neurodegenerative diseases.

PMID- 15850678
TI  - Closed head injury--an inflammatory disease?
AB  - Closed head injury (CHI) remains the leading cause of death and persisting
      neurological impairment in young individuals in industrialized nations. Research
      efforts in the past years have brought evidence that the intracranial
      inflammatory response in the injured brain contributes to the neuropathological
      sequelae which are, in large part, responsible for the adverse outcome after head
      injury. The presence of hypoxia and hypotension in the early resuscitative period
      of brain-injured patients further aggravates the inflammatory response in the
      brain due to ischemia/reperfusion-mediated injuries. The profound endogenous
      neuroinflammatory response after CHI, which is phylogenetically aimed at
      defending the intrathecal compartment from invading pathogens and repairing
      lesioned brain tissue, contributes to the development of cerebral edema,
      breakdown of the blood-brain barrier, and ultimately to delayed neuronal cell
      death. However, aside from these deleterious effects, neuroinflammation has been
      recently shown to mediate neuroreparative mechanisms after brain injury as well.
      This "dual effect" of neuroinflammation was the focus of extensive experimental
      and clinical research in the past years and has lead to an expanded basic
      knowledge on the cellular and molecular mechanisms which regulate the
      intracranial inflammatory response after CHI. Thus, head injury has recently
      evolved as an inflammatory and immunological disease much more than a pure
      traumatological, neurological, or neurosurgical entity. The present review will
      summarize the so far known mechanisms of posttraumatic neuroinflammation after
      CHI, based on data from clinical and experimental studies, with a special focus
      on the role of pro-inflammatory cytokines, chemokines, and the complement system.

PMID- 15850679
TI  - Activity of flurbiprofen and chemically related anti-inflammatory drugs in models
      of Alzheimer's disease.
AB  - Currently, there is an intense debate on the potential use of nonsteroidal anti
      inflammatory drugs (NSAIDs) in Alzheimer's disease (AD). NSAIDs are among the
      most widely prescribed drugs for the treatment of pain, fever, and inflammation.
      Their effects are largely attributed to the inhibition of the enzymatic activity
      of cyclooxygenase (COX)-1 and -2. The apparent activity of this class of drugs
      stems from one critical pathological process underlying AD and other
      neurodegenerative disorders, i.e., the presence of chronic neuroinflammation. In
      fact, prolonged use of NSAIDs is associated with reduced risk of AD. Besides COX
      inhibition, additional mechanisms could contribute to the potential activity of
      NSAIDs in AD. For example, several studies show that only a few selected NSAIDs
      also affect beta-amyloid (Abeta) deposition and metabolism. Among the Abeta
      effective NSAIDs, flurbiprofen raised particular interest because of its multiple
      actions on key AD hallmarks. Studies in cell lines and animal models have shown
      that flurbiprofen racemate, its R-enantiomer and its nitric oxide (NO)-releasing
      derivatives, HCT 1026 and NCX 2216, are effective on AD amyloid pathology.
      Moreover, HCT 1026 and NCX 2216 differentially influence the cellular component
      of neuroinflammation (i.e., microglia activation) in some experimental settings,
      i.e., HCT 1026 inhibits the activation of microglia, while NCX 2216 can either
      enhance or inhibit microglial activation, depending upon the experimental
      conditions. It is still unclear which effects on microglia will prove most
      beneficial. Ultimately, clinical studies in AD patients will provide the best
      information as to whether selected NSAIDs will improve this devastating disease.

PMID- 15850680
TI  - Otorhinolaryngological manifestations of the mucopolysaccharidoses.
AB  - The mucopolysaccharidoses (MPS) are a family of related inherited metabolic
      disorders where, due to specific lysosomal enzyme deficiencies, partially
      degraded glycosaminoglycans (GAGs) accumulate in the body's cells. Due to the
      ubiquitous nature of GAGs in the body this deposition can occur in many tissue
      types and may interfere with cellular function. Although these conditions are
      rare, there is a propensity for the disease process to cause problems with the
      function of the ears, noses and throats of affected patients. In this review, we
      present an overview of the clinical manifestations of MPS in general and
      highlight the problems specifically presenting in the field of
      otorhinolaryngology.

PMID- 15850681
TI  - Extraesophageal acid reflux and recurrent respiratory papilloma in children.
AB  - OBJECTIVE: Recurrent respiratory papillomatosis (RRP) is a benign infectious
      disease which is caused by the human papilloma virus (HPV). When it infects the
      larynx, hoarseness and airway obstruction are often the presenting symptoms.
      Latent virus is found in the laryngeal mucosa of many more patients than exhibit
      the disease. The factors which lead to virus activation have not been identified,
      however, extra-esophageal acid reflux disease (EERD) has been suggested as one of
      these factors. METHODS: This is a case series of four patients with RRP who had
      increase in severity of their disease with the recognition of concurrent extra
      esophageal acid reflux. The clinical course of the papillomatosis and the
      diagnosis and treatment of reflux are compared over time. RESULTS: In all four
      cases, with identification and treatment of the EERD, control of the RRP
      improved, and in at least two patients, was complete with resolution of the EERD.
      Lapses in compliance with medications or behavioral and dietary recommendations
      in three out of four patients led to a rebound in symptoms and signs of RRP,
      including worsening of vocal quality and the endoscopic appearance of the larynx.
      CONCLUSION: The clinical course of these patients suggests a link between the
      presence of EERD and RRP. The inflammation induced by chronic acid exposure may
      result in the expression of HPV in susceptible tissues. Prompt diagnosis and
      effective treatment of EERD should be considered in all patients with difficult
      to control RRP or with clinical presentation or endoscopic signs of EERD.

PMID- 15850682
TI  - A single-center 6-year experience with two types of pediatric tracheostomy.
AB  - OBJECTIVE: Among a wide variety of tracheostomy techniques, a vertical tracheal
      incision and a horizontal incision with creation of an inferior base tracheal
      flap have been favorized in children in the past. The aim of this study was to
      determine surgical and postoperative stoma complications after performing these
      two types of tracheal incision in tracheostomy in children. METHODS: A 6-year,
      prospective, observational cohort study was undertaken in 24 children (range,
      0.03 month-15 years) at the Department of Otorhinolaryngology, University of Ulm.
      All children who underwent an elective tracheostomy were included in this study.
      Early and late local disorders in wound healing of the tracheal stoma and the
      clinical follow-up of both groups (Flap group and Vertical group) were analyzed.
      RESULTS: Formation of granulation tissue and tracheal stenosis were the most
      observed local disorders in both groups. Granulation tissue at the level of the
      stoma was the most frequently observed complication in the Flap group (4/12;
      33%), whereas in the Vertical group only one child showed granulation tissue
      around the stoma (1/7; 14%). The difference between both groups was statistically
      not significant. The overall mortality rate 1 year after tracheostomy was 25%
      (6/24) and the tracheostomy-related death rate was 4% (1/24). An association of
      wound healing disorders with a feasible lethal outcome was not found after both
      tracheostomy types. There were no differences in the outcome between both
      tracheal incision types. CONCLUSIONS: Both types of tracheal incision proved to
      be a suitable surgical procedure for temporary or permanent tracheostomy in
      pediatric patients.

PMID- 15850683
TI  - Brain auditory evoked potentials in children with Down syndrome.
AB  - Researchers have been examining the condition of the auditory organ in people
      with Down syndrome for many years. The aim of this work was an objective
      evaluation of the hearing threshold and a functional evaluation of the hearing
      pathway in children with Down syndrome without any disturbances in the middle
      ear. MATERIAL: Seventy children with Down syndrome, aged from 2 months to 17
      years. Brain auditory evoked potentials (BAEP) were performed. The peak latencies
      in children who had a normal BAEP pattern at 70 dB sHL were analysed. Peaks I-III
      and interpeak latencies I-III were significantly shortened in Down syndrome
      children up to the age of 1 year, as compared to older children with Down
      syndrome and to the control group. Peak III and interpeak latencies I-III were
      significantly longer in older children with Down syndrome in comparison to the
      control group. CONCLUSIONS: Hearing loss in children with Down syndrome is more
      frequent than in healthy children. The average latency values of BAEP established
      for healthy children should not be used as a reference for children with Down
      syndrome. The shortening of the latency values in BAEP results of children with
      Down syndrome under 1 year of age may be connected with accelerated maturation of
      the nervous system or anatomical and/or functional disturbances of the central
      nervous system. BAEP is a valuable method that allows for the objective
      evaluation of the hearing threshold and functional condition of the hearing
      pathway in subjects who do not cooperate during testing.

PMID- 15850684
TI  - Nuclear and mitochondrial genes mutated in nonsyndromic impaired hearing.
AB  - Half of the cases with congenital impaired hearing are hereditary (HIH). HIH may
      occur as part of a multisystem disease (syndromic HIH) or as disorder restricted
      to the ear and vestibular system (nonsyndromic HIH). Since nonsyndromic HIH is
      almost exclusively caused by cochlear defects, affected patients suffer from
      sensorineural hearing loss. One percent of the total human genes, i.e. 300-500,
      are estimated to cause syndromic and nonsyndromic HIH. Of these, approximately
      120 genes have been cloned thus far, approximately 80 for syndromic HIH and 42
      for nonsyndromic HIH. In the majority of the cases, HIH manifests before
      (prelingual), and rarely after (postlingual) development of speech. Prelingual,
      nonsyndromic HIH follows an autosomal recessive trait (75-80%), an autosomal
      dominant trait (10-20%), an X-chromosomal, recessive trait (1-5%), or is
      maternally inherited (0-20%). Postlingual nonsyndromic HIH usually follows an
      autosomal dominant trait. Of the 41 mutated genes that cause nonsyndromic HIH, 15
      cause autosomal dominant HIH, 15 autosomal recessive HIH, 6 both autosomal
      dominant and recessive HIH, 2 X-linked HIH, and 3 maternally inherited HIH.
      Mutations in a single gene may not only cause autosomal dominant, nonsyndromic
      HIH, but also autosomal recessive, nonsyndromic HIH (GJB2, GJB6, MYO6, MYO7A,
      TECTA, TMC1), and even syndromic HIH (CDH23, COL11A2, DPP1, DSPP, GJB2, GJB3,
      GJB6, MYO7A, MYH9, PCDH15, POU3F4, SLC26A4, USH1C, WFS1). Different mutations in
      the same gene may cause variable phenotypes within a family and between families.
      Most cases of recessive HIH result from mutations in a single locus, but an
      increasing number of disorders is recognized, in which mutations in two different
      genes (GJB2/GJB6, TECTA/KCNQ4), or two different mutations in a single allele
      (GJB2) are involved. This overview focuses on recent advances in the genetic
      background of nonsyndromic HIH.

PMID- 15850685
TI  - A two-step scenario for hearing assessment with otoacoustic emissions at
      compensated middle ear pressure (in children 1-7 years old).
AB  - OBJECTIVE: Otoacoustic emissions (OAEs) are widely used for assessing congenital
      and early-acquired sensorineural hearing loss in young children. Middle ear
      pathology has a negative effect on the presence of OAEs. In this study we
      investigated whether measuring OAEs at compensated middle ear pressure (CMEP)
      resulted in a higher pass rate than at ambient pressure. Secondly, we analysed
      the influence of 12 different pass definitions on the pass rates. METHODS: One
      hundred and eleven children (age 1-7 years, mean 4 years and 5 months) were
      measured twice in one session: first at ambient pressure and then at CMEP.
      RESULTS: The study showed a higher pass rate of OAEs at CMEP than at ambient
      pressure. A two-step scenario reduced the number of fails by 18-26%, depending on
      the pass/fail definition used. CONCLUSION: Measuring OAEs at CMEP results in
      higher pass rates. Secondly, pass/fail definitions have a large influence on pass
      rates and this issue deserves further attention. Further studies must be done,
      before this method is readily applicable to universal neonatal screening.

PMID- 15850686
TI  - Plastic laryngeal foreign bodies in children: a diagnostic challenge.
AB  - OBJECTIVE: To review Children's Hospital and Regional Medical Center experience
      with pediatric airway foreign bodies, and examine the incidence and treatment of
      laryngeal foreign bodies. To determine if plastic laryngeal foreign bodies
      present differently than other laryngeal foreign bodies. METHODS: A retrospective
      review of all cases of children (1874 patients) undergoing direct laryngoscopy
      and/or bronchoscopy from 1st January 1997 to 9th September 2003 at a tertiary
      care children's hospital. Patients with endoscopically documented laryngeal
      foreign bodies were identified and the medical record reviewed in more detail.
      Patient age, gender, foreign body location, foreign body type, duration of
      foreign body presence, radiographic findings, endoscopic findings and treatment
      complications were recorded. RESULTS: One hundred and five aspirated foreign
      bodies were identified. The nine laryngeal foreign bodies included five clear
      plastic radiolucent items, two radiolucent food items, and two sharp radioopaque
      pins. Time to diagnosis and treatment was on average 11.6 days with 17.6 days for
      thin/plastic foreign bodies and 1.6 days for metal/food foreign bodies.
      CONCLUSION: Laryngeal foreign bodies represent a small portion of all pediatric
      airway foreign bodies. Difficulty in identifying laryngeal foreign bodies,
      especially thin, plastic radiolucent foreign bodies can delay treatment. Thin
      plastic foreign bodies can present without radiographic findings, can be
      difficult to image during endoscopy and can be particularly difficult to
      diagnose. A history of choking and vocal changes is associated with laryngeal
      foreign bodies. Laryngeal foreign bodies should be in the differential diagnosis
      of all children presenting with atypical upper respiratory complaints especially
      if a history suggestive of witnessed aspiration and dysphonia can be obtained.

PMID- 15850688
TI  - Pediatric oropharyngeal trauma: what is the role of CT scan?
AB  - OBJECTIVES/HYPOTHESIS: Pediatric oropharyngeal trauma (OPT) is a common injury in
      children with rare, but at times severe complications including carotid injury
      and dissection of air/micro-organisms into the deep tissues of the neck or chest.
      Cervical CT scan with contrast (CT angiography (CTA)) is nearly universally
      available and may enhance the evaluation of OPT patients by screening for these
      potentially devastating complications. STUDY DESIGN: Retrospective record review,
      systematic review of the literature. METHODS: Twenty-three patients diagnosed
      with OPT from 1997 to 2003 at Boston Children's Hospital were identified by
      database review. Records were reviewed for site and mechanism of injury, use of
      diagnostic studies, management, and outcomes. Results were compared to previously
      published reports. The current literature was reviewed to assess the level of
      evidence pertaining to the evaluation of OPT patients with CT scan. An
      extrapolation was made to the general trauma literature to further evaluate the
      ability of CT angiography to detect carotid injury. RESULTS: Demographics and
      mechanism of injury in the current series were unchanged from previous reports.
      CT demonstrated superior detection and localization of free air. Systematic
      review of OPT literature revealed data on the use of CT scan as evaluation tool
      were lacking. Extrapolations to the trauma literature strongly indicate helical
      CTA has high sensitivity and specificity in detecting carotid injury.
      CONCLUSIONS: Pediatric oropharyngeal trauma is a common injury with rare, but
      severe complications. The routine use of CT scan with contrast may assist in the
      evaluation of these patients to detect injuries that could lead to severe
      complications. Collection of prospective data on the ability of CT scan to detect
      carotid injuries is needed but may not be feasible.

PMID- 15850687
TI  - Management of an "Ear Camp" for children in Namibia.
AB  - OBJECTIVE: In this publication, we present our experiences with managing an "Ear
      Camp" in northern Namibia, where the population is predominantly black. Medical
      coverage for ear problems is poor in this part of the country. METHODS: Within 10
      days, 38 children (median age 12 years) were operated mainly for (sub) total
      defects of the tympanic membrane. In two cases, an open cavity had to be created
      because of a cholesteatoma. We performed a tympanoplasty type I in 18 cases and a
      tympanoplasty type III in 20 cases. Additionally, in 8 cases an antrotomy and in
      another 8 cases a mastoidectomy was performed. The ossicular chain was
      reconstructed with a titanium-PORP (14 cases), a titanium-TORP, interposition of
      the head of the malleus or a cartilage columella (one case each) or by placing
      the reconstructed tympanic membrane directly onto the head of the stapes (three
      cases). The tympanic membrane was reconstructed by the use of tragal cartilage
      with overlapping perichondrium in underlay-technique. RESULTS: Thirty-one
      children could be followed up. A defect of the tympanic membrane was found in
      five cases because of continuous purulent discharge. The average improvement of
      air conduction thresholds in the frequencies between 250 and 4000 Hz was 15 dB.
      CONCLUSIONS: Surgical techniques, antibiotic treatment and perioperative
      management have to be adapted to limited possibilities of pre-treatment and
      aftercare. As development aid should support people to look after themselves, we
      started to instruct local doctors with regard to pre- and postoperative care in
      ear surgery. Training of the local doctors will be continued in our next "Ear
      Camp" in 2004.

PMID- 15850689
TI  - The neonate cry after cesarean section and vaginal delivery during the first
      minutes of life.
AB  - Although the option for vaginal delivery is most physiological, the achievement
      of cesarean section is very common in Brazil. The neonate cry represents the
      beginning of both processes, physiological adaptation and human vocal
      communication. The cry emission depends on the functioning of respiratory and
      laryngeal muscles, which are controlled by the nervous system. The acoustic
      analysis of neonate cry is useful in the assessment of healthy babies and can be
      used to characterize the signals of diseases through a previously
      multidisciplinary diagnosis, with immediate medical intervention. The present
      study compared the acoustic cry characteristics of 30 healthy newborn after a
      cesarean section and 30 healthy newborn after a vaginal delivery, of both
      genders, from the exact moment of birth until the first 5 min of life. Using the
      softwares VOXMETRIA and GRAM, it was possible to analyze the duration, frequency,
      intensity, occurrence, localization and inspiratory phonation, besides the type
      of spectrographic tracings. The acoustic cry characteristics of newborns after a
      C section and a vaginal delivery could evidence not only harmonic, expiratory,
      acute and strong emissions, but also emissions rich in sounds and varied in types
      of melody. The differences found can be related to the physiology of birth.

PMID- 15850690
TI  - An unusual case of bilateral submandibular sialolithiasis in a young female
      patient.
AB  - Salivary calculi in the pediatric population comprise only 3% of all cases of
      sialolithiasis. In addition, the presentation of bilateral calculi in children is
      rare. The formation of stones in the salivary glands has been attributed to slow
      salivary flow, salivary stagnation and unknown metabolic events. There is no
      report in the literature of an association between dietary calcium intake and
      calculi formation. We describe the clinical findings and management in a patient
      with bilateral sialolithiasis thought to be linked to high dietary calcium intake
      and review the literature.

PMID- 15850691
TI  - Precursor B-cell lymphoblastic lymphoma presenting as an isolated external ear
      swelling in a two-year-old child.
AB  - The incidence of lymphoma in children is increasing in the United States and is
      the third most common childhood cancer. The head and neck is second only to the
      abdomen as the most common site of extranodal presentations of non-Hodgkin's
      lymphoma (NHL). We present and discuss the diagnosis and management of the first
      report of a child with an auricular mass as the sole manifestation of B-cell non
      Hodgkin's lymphoma. In summary, the otolaryngologist and pediatrician should be
      cognizant of potential for NHL in atypical lesions of the head and neck in
      children.

PMID- 15850692
TI  - Actinomycotic abscess of the thyroid gland in an infant.
AB  - Actinomycotic abscess of the thyroid gland is rare especially in childhood. In
      this article, we report the second pediatric case in literature, at age of 18
      months. Although spread of actinomycotic infection to the thyroid gland from
      upper aerodigestive tract by preformed pathways such as piriform sinus fistula
      seems rational, it was demonstrated neither in current nor in previous cases.
      Therefore, further work-up such as barium swallow, which is onerous to perform in
      a child may be reserved for recurrent cases.

PMID- 15850694
TI  - Redundant publications in Otolaryngology--Head and Neck Surgery.

PMID- 15850693
TI  - Familial Parry-Romberg disease.
AB  - Parry-Romberg disease (or hemifacial atrophy) is a rare condition affecting the
      face. It commences in childhood but its aetiology remains unknown, and is
      sporadic. Two cases are presented who were biological first cousins. We believe
      that this is the first recorded example of this condition occurring in family
      members.

PMID- 15850696
TI  - Effect of intranasal corticosteroid on bronchial hyper-responsiveness in allergic
      rhinitis.

PMID- 15850698
TI  - Structure of Anisakis simplex s.l. populations in a region sympatric for A.
      pegreffii and A. simplex s.s. Absence of reproductive isolation between both
      species.
AB  - The aim of this study was to determine the genetic structure of A. simplex s.l.
      populations. This was done by applying PCR-RFLP and RAPD-PCR to 42 specimens
      morphologically identified as third stage larvae of A. simplex s.l. Of these
      larvae, 59.26% of those of Mediterranean origin are identified by PCR-RFLP as A.
      pegreffii. In Atlantic waters, this percentage dropped to 20.00% while A. simplex
      s.s. represents 66.67%. However, findings seem to suggest that the taxonomic
      status of both species should be reconsidered owing to: (i) the high gene flow
      value that we detected between A. simplex s.s. and A. pegreffii; (ii) the short
      genetic distance between both members of the A. simplex complex; (iii) the fact
      that hybrid genotypes represent 16.67% of the parasites analyzed and are
      represented in all the populations studied, except for the Cantabrian one. When
      the genetic variation is estimated between the 42 individual A. simplex s.l.
      specimens studied these can be classified into four groups. The genetic distances
      and gene flow between three of them are compatible with the existence of three
      different genetic populations. The fourth is comprised of a single specimen of
      L3, identified both by PCR-RFLP and by RAPD-PCR as a new genotype.

PMID- 15850699
TI  - The FK506-binding protein of the malaria parasite, Plasmodium falciparum, is a
      FK506-sensitive chaperone with FK506-independent calcineurin-inhibitory activity.
AB  - We have identified an immunophilin of the FKBP family in Plasmodium falciparum
      that contains a conserved peptidyl prolyl isomerase (PPIase) and
      tetratricopeptide repeat (TPR) domains. The 35 kDa protein was named FKBP35 and
      expressed in bacteria. Recombinant FKBP35 exhibited potent PPIase and protein
      folding activities against defined substrates in vitro, suggesting that it is a
      parasitic chaperone. Both activities were inhibited by macrolide
      immunosuppressant drugs, ascomycin (a FK506 derivative) and rapamycin, but not by
      cyclosporin A, providing biochemical evidence of its inclusion in the FKBP
      family. Interestingly, FKBP35 inhibited purified plasmodial calcineurin (protein
      phosphatase 2B) in the absence of any drug. In the parasite's cell, FKBP35
      exhibited a stage-specific nucleocytoplasmic shuttling and did not co-localize
      with calcineurin. FKBP35 associated with plasmodial heat shock protein 90
      (Hsp90), another member of the chaperone superfamily, via the TPR domain.
      Geldanamycin, a Hsp90 inhibitor, and ascomycin inhibited P. falciparum growth in
      a synergistic fashion. Extensive search of the P. falciparum genome revealed no
      other FKBP sequence, implicating PfFKBP35 as a highly significant antimalarial
      drug target. Thus, the single FKBP of Plasmodium is an essential parasitic
      chaperone with a novel drug-independent calcineurin-inhibitory activity.

PMID- 15850700
TI  - E. dispar strain: analysis of polymorphism as a tool for study of geographic
      distribution.
AB  - The intra-species polymorphism of E. histolytica and E. dispar species in endemic
      area is an important tool for geographic distribution and spread mechanism
      studies. Since E. dispar and E. histolytica shears ecological niche, cell cycle,
      and transmission mechanism for human host, we studied the intra-specie variation
      and distribution of E. dispar strains obtained from cyst passers, in two neighbor
      rural communities in Morelos Mexico. We analyzed the polymorphic region of the
      quitinase protein gene in isolates of E. dispar. In 45 isolates from one
      community we identified 12 different CHI patterns while in 15 isolates from the
      other community we identified 5 different patterns. However both communities
      share 4 patterns. This finding suggests the presence of strains with different
      geographic mobility.

PMID- 15850701
TI  - A role for poly(dA)poly(dT) tracts in directing activity of the Plasmodium
      falciparum calmodulin gene promoter.
AB  - Expression of the Plasmodium falciparum calmodulin gene (pfcam) is
      developmentally regulated throughout the blood-stage cycle. The promoter lies
      within approximately 1 kb of intergenic sequence that separates the pfcam open
      reading frame (ORF) from an upstream inverted ORF encoding a product homologous
      to the co-chaperone STI1. Using the oligo-capping method, which selectively
      reverse-transcribes cDNA from only full-length, capped transcript, we have mapped
      multiple transcription-initiation sites for both genes. Transcription of the
      pfSTI1 gene initiates over a 150 bp region centred approximately 350 bp upstream
      of the ORF. The pfcam transcription start sites cluster into four approximately
      30 bp regions lying within 180 bp upstream of the pfcam ORF, generating
      transcripts with 5' untranslated regions (UTR) of 3-173 nucleotides in length.
      Remarkably, splicing was found to be related to UTR length, with apparent
      preferential splicing of longer transcripts. Activity of the pfcam promoter
      diminished in a linear fashion to undetectable levels upon step-wise removal of
      sequence between 625 and 230 bp upstream of the start ATG. Electromobility-shift
      assays demonstrated nuclear factor binding to eight oligonucleotide probes
      spanning 657 bp of the pfcam ORF proximal upstream sequence. The degree of
      binding correlated with the density of poly(dA)poly(dT) tracts within the probes,
      and in all cases could be inhibited by excess synthetic poly(dA)poly(dT), but not
      by poly(dAdT)poly(dAdT). The multiple transcription-initiation sites of both
      pfSTI1 and pfcam genes lie just downstream of 25 bp-long poly(dA)poly(dT) tracts,
      and the intergenic region contains over 20 poly(dA)poly(dT) tracts of 4 bp or
      more. Our results suggest that the basal pfcam promoter is situated between
      approximately -300 and -230 bp upstream of the pfcam ORF and that the P.
      falciparum transcription-initiation complex has a low degree of sequence
      specificity for the sites of initiation but preferentially acts downstream of
      long poly(dA)poly(dT) tracts.

PMID- 15850702
TI  - Overexpression of AP endonuclease protects Leishmania major cells against
      methotrexate induced DNA fragmentation and hydrogen peroxide.
AB  - Generation of abasic (AP) sites is one of the main anomalies to arise in cellular
      DNA. These lesions are highly mutagenic, and need to be repaired by the base
      excision repair (BER) system. Oxidative stress and misincorporation of dUTP are
      important sources of mutation load trough generation of AP sites. Kinetoplastid
      protozoa are able to survive in a highly oxidative environment within the host
      macrophages and between the different strategies used for survival, active DNA
      repair mechanisms must exist. In order to assess the role of BER in protecting
      parasites against DNA damage, we have overexpressed one enzyme of the pathway, AP
      endonuclease, in Leishmania major. Parasites overproducing AP endonuclease of L.
      major (APLM) showed an increased resistance to hydrogen peroxide, a mutagen that
      produces oxidative stress, and also to methotrexate (MTX), an inhibitor of
      thymidylate biosynthesis which causes a massive incorporation of dUTP into DNA,
      when compared to control cells. Moreover, DNA fragmentation caused by MTX was
      prevented in cells overexpressing APLM. Our results suggest that APLM is a key
      enzyme in mediating repair of AP sites in these pathogens.

PMID- 15850703
TI  - Developmental changes in the adhesive disk during Giardia differentiation.
AB  - Giardia lamblia is a protozoan parasite infecting the upper mammalian small
      intestine. Infection relies upon the ability of the parasite to attach to the
      intestine via a unique cytoskeletal organelle, the ventral disk. We determined
      the composition and structure of the disk throughout the life cycle of the
      parasite and identified a new disk protein, SALP-1. SALP-1 is an immunodominant
      protein related to striated fiber-assemblin (SFA). The disk is disassembled
      during encystation and stored as four fragments in the immobile cyst. Serial
      Analysis of Gene Expression (SAGE) showed that the mRNA levels of the disk
      proteins decreased in encystation but two-dimensional protein gels showed that
      the protein levels were more constant. The parasite emerges without a functional
      disk but the four disk fragments are quickly reassembled into two new disks on
      the dividing, early excysting form. Thus, disk proteins are stored within the
      cyst, ready to be used in the rapid steps of excystation.

PMID- 15850704
TI  - Atomic force microscopy imaging and 3-D reconstructions of serial thin sections
      of a single cell and its interior structures.
AB  - The thin sectioning has been widely applied in electron microscopy (EM), and
      successfully used for an in situ observation of inner ultrastructure of cells.
      This powerful technique has recently been extended to the research field of
      atomic force microscopy (AFM). However, there have been no reports describing AFM
      imaging of serial thin sections and three-dimensional (3-D) reconstruction of
      cells and their inner structures. In the present study, we used AFM to scan
      serial thin sections approximately 60 nm thick of a mouse embryonic stem (ES)
      cell, and to observe the in situ inner ultrastructure including cell membrane,
      cytoplasm, mitochondria, nucleus membrane, and linear chromatin. The high
      magnification AFM imaging of single mitochondria clearly demonstrated the outer
      membrane, inner boundary membrane and cristal membrane of mitochondria in the
      cellular compartment. Importantly, AFM imaging on six serial thin sections of a
      single mouse ES cell showed that mitochondria underwent sequential changes in the
      number, morphology and distribution. These nanoscale images allowed us to perform
      3-D surface reconstruction of interested interior structures in cells. Based on
      the serial in situ images, 3-D models of morphological characteristics, numbers
      and distributions of interior structures of the single ES cells were validated
      and reconstructed. Our results suggest that the combined AFM and serial-thin
      section technique is useful for the nanoscale imaging and 3-D reconstruction of
      single cells and their inner structures. This technique may facilitate studies of
      proliferating and differentiating stages of stem cells or somatic cells at a
      nanoscale.

PMID- 15850705
TI  - Mapping the 3D-surface strain field of patterned tensile stainless steels using
      atomic force microscopy.
AB  - The quantification of microstructural strains at the surface of materials is of
      major importance for understanding the reactivity of solids. The present paper
      aims at demonstrating the potentialities of the atomic force microscopy (AFM) for
      mapping the three-dimensional surface strain field on patterned tensile
      specimens. Electron beam (e-beam) lithography has been used to deposit 16 x 16
      arrays of gold-squared pads. Monitoring the evolution of such a pattern under
      applied strain allows to quantify the triaxial strains both at the micro
      (plastic) domain and nanoscale (elastic) domain vs. applied strain. The proposed
      method was applied to stainless steels after 4.5% plastic strain.

PMID- 15850706
TI  - Charge and charging compensation on oxides and hydroxides in oxygen environmental
      SEM.
AB  - Oxygen environment was applied to the scanning electron microscopy (SEM) analysis
      of insulating samples. In the high vacuum SEM, a local oxygen pressure was
      provided, and in the environmental SEM, oxygen atmosphere was used instead of
      water, the commercial mode. The charging effects in the SEM observation and
      component characterization of samples such as Al(2)O(3), Al(OH)(3), Mg(OH)(2) and
      others can be eliminated or significantly reduced. The oxygen environment does
      not only provide a new approach to releasing the charging difficulty in the
      analyses using electron beam as a probe, but also provide an insightful hint to
      the understanding of the charging processes in general.

PMID- 15850707
TI  - Nondestructive three-dimensional characterization of grain boundaries by X-ray
      crystal microscopy.
AB  - The results from an emerging method of nondestructive grain boundary
      characterization, with unprecedented sensitivity to neighbor-grain misorientation
      and grain boundary morphology are reported. The method utilizes differential
      aperture X-ray microscopy to determine the local crystallographic orientation of
      submicron volumes within polycrystalline materials. Initial measurements are
      described for a recrystallized Ni sample where the grain boundary type was
      identified at 85 grain boundaries within the framework of an ideal coincident
      site lattice (CSL) model. The remarkable resolution of this method is
      demonstrated by the <0.03 degrees deviations of misorientation measured for
      Sigma3 (twin) boundaries. Because of its high angular and spatial resolution,
      this new approach to grain boundary characterization can provide quantitative
      tests of grain boundary models with new insights for grain boundary engineering
      efforts.

PMID- 15850708
TI  - The determination of the size and shape of buried InAs/InP quantum dots by
      transmission electron microscopy.
AB  - Bright-field, diffraction-contrast imaging in the transmission electron
      microscope has been applied to the determination of the diameter and height
      populations of a single layer of buried, pure, InAs/InP quantum dots (QDs). Plan
      view diffraction contrast from the QDs was observed to increase significantly
      when the sample was tilted away from the [001] growth direction to near the [111]
      zone-axis orientation. This added contrast was a result of contributions to the
      displacement of atoms in a direction perpendicular to the electron beam arising
      from strain in the growth direction. Since the strain in the growth direction was
      about an order of magnitude larger than the strain perpendicular to the growth
      direction, as the sample is tilted away from the [001] zone-axis condition, the
      larger strain component increases the projected strain thereby increasing the QD
      contrast in the image. For the sample studied, both of the populations for the QD
      diameter and the image contrast were observed to be multimodal with the seven
      peaks in the contrast distribution correlating with seven distinct populations of
      QDs each differing in height by one monolayer (ML), from 3 to 9MLs. An analysis
      of the theoretically expected and experimentally observed standard deviations in
      the Gaussian fits to the QD diameter and height distributions provided an
      additional constraint in the selection of the optimal model for the multimodal
      distributions.

PMID- 15850709
TI  - Effect of tip shape on capacitance determination accuracy in scanning capacitance
      microscopy.
AB  - We present an analysis of the measurement error caused by the stray field of
      scanning capacitance microscope probes of various shapes. Cylindrical islands and
      wells of varying radius and height or depth, in both conducting surfaces and
      structures containing dielectric films, were used as test features for modelling.
      The results show that high accuracy and good contrast of small details are
      contradictory requirements. Probes with small radius of curvature of the tip apex
      yield smaller errors on features with small diameter but larger ones on features
      with large diameter than tips with large radius of curvature. The stray
      electrostatic field causes large errors, which are exceptionally severe with
      microfabricated probes. Contrary to general belief, differential measurements,
      based on modulation of the probe/sample separation or of the width of depletion
      layer in semiconductors, do not reduce the effect of the stray field
      significantly. For best results, the probe should be shielded as close to the tip
      apex as possible. In the case of microfabricated probes, at least the side of the
      cantilever facing the sample should be shielded.

PMID- 15850710
TI  - Shear force microscopy with a nanoscale resolution.
AB  - This paper presents a shear force microscope having a nanometric resolution at
      high scan rates. Current techniques were reviewed and tested, and a design based
      on the use of a tuning fork is described. The use of a low quality factor enabled
      us to decrease the response time and increase the stability of the tracking. The
      microscope was coupled with a tunneling current detection, in order to study the
      interactions between the sample and the probe during scanning. As an example, a
      sharp nickel nanotip was used to image a gold surface, showing details down to a
      few nanometers, even at scanning rates of 4Hz.

PMID- 15850711
TI  - Consistent indexing of a (set of) single crystal SAED pattern(s) with the
      ProcessDiffraction program.
AB  - A computer program called "ProcessDiffraction" helps indexing a set of single
      crystal selected area electron diffraction (SAED) patterns by determining which
      of the presumed structures can fit all the measured patterns simultaneously.
      Distances and angles are measured in the digitalized patterns with a graphical
      tool by clicking on the two shortest non-collinear vectors (spots), using user
      supplied calibration data. Centers of the spots and center of the pattern are
      optionally refined by the program. Suggested individual indexing solutions
      (consistent with an assumed unit cell) are listed by the program for each
      pattern. Simulated patterns are also consulted to check if the shortest
      calculated distances coincide with measured ones. Common solutions for the set
      are selected by checking the angles between the suggested zone axes against the
      angles between the experimental goniometer settings. The indexing process is
      manually controlled by selecting the candidate structures (one-by-one) for
      indexing and by specifying the tolerances for d-values, plane angles and zone
      angles. Patterns of any crystal system can be indexed successfully. Although
      error bars are larger in electron diffraction than in X-ray diffraction (XRD),
      frequently, many unrelated indexings are possible for any one electron
      diffraction pattern (irrespective of the indexing method), a set of SAED patterns
      can generally be indexed unambiguously, i.e. the three-dimensional reciprocal
      space can be identified correctly. Two other tools also help planning tilting
      experiments: zones along a plane can be listed (with their angles extended from a
      pre-selected zone in that plane) and zones lying at a given angle (specified with
      a tolerance) from a zone can also be identified (as they are situated between two
      cones). Another tool searches the XRD database directly either for advice on
      possible structures for a composition or to help calibration.

PMID- 15850712
TI  - New insights into the retinal circulation: inflammatory lipid mediators in
      ischemic retinopathy.
AB  - Ischemic proliferative retinopathy develops in various retinal disorders,
      including retinal vein occlusion, diabetic retinopathy and retinopathy of
      prematurity. Ischemic retinopathy remains a common cause of visual impairment and
      blindness in the industrialized world due to relatively ineffective treatment.
      Oxygen-induced retinopathy (OIR) is an established model of retinopathy of
      prematurity associated with vascular cell injury culminating in microvascular
      degeneration, which precedes an abnormal neovascularization. The retina is a
      tissue particularly rich in polyunsaturated fatty acids and the ischemic retina
      becomes highly sensitive to lipid peroxidation initiated by oxygenated free
      radicals. Consequently, the retina constitutes an excellent model for testing the
      functional consequences of membrane lipid peroxidation. Retinal tissue responds
      to physiological and pathophysiological stimuli by the activation of
      phospholipases and the consequent release from membrane phospholipids of
      biologically active metabolites. Activation of phospholipase A(2) is the first
      step in the synthesis of two important classes of lipid second messengers, the
      eicosanoids and a membrane-derived phospholipid mediator platelet-activating
      factor (PAF). These lipid mediators accumulate in the retina in response to
      injury and a physiologic role of these metabolites in retinal vasculature remains
      for the most part to be determined; albeit proposed roles have been suggested for
      some. The eicosanoids, in particular the prostanoids, thromboxane (TXA2) and PAF
      are abundantly generated following an oxidant stress and contribute to
      neurovascular injury. TXA2 and PAF play an important role in the retinal
      microvacular degeneration of OIR by directly inducing endothelial cell death and
      potentially could contribute to the pathogenesis of ischemic retinopathies.
      Despite these advances there are still a number of important questions that
      remain to be answered before we can confidently target pathological signals. This
      review focuses on mechanisms that precede the development of neovascularization,
      most notably regarding the role of lipid mediators that partake in microvascular
      degeneration.

PMID- 15850713
TI  - Bile duct ligation induced acute inflammation up-regulates cyclooxygenase-2
      content and PGE2 release in guinea pig gallbladder smooth muscle cell cultures.
AB  - INTRODUCTION: This study examines hypotheses that BDL induces increased guinea
      pig gallbladder smooth muscle PGE2 release by up-regulation of COX-2. METHODS:
      BDL, Sham and Control Hartley guinea pig gallbladders were placed in cell
      culture, grown to confluence and underwent Western Blot analysis for smooth
      muscle cell content of COX-1, COX-2, Prostacylin Synthase, actin, caldesmon,
      vinculin, meta-vinculin and tropomyosin and were assayed for basal release of 6
      keto-PGF(1alpha), PGE2 and TxB2 by EIA. RESULTS: BDL did not alter content of
      smooth muscle cytoskeletal proteins. BDL for 48 h increased smooth muscle cell
      release of PGE2 and 6-keto-PGF(1alpha) by 3-fold or more when compared to the
      Control and Sham groups. Western Blot analysis showed increased content of COX-2
      in the BDL group. CONCLUSIONS: BDL for 48 h markedly increased endogenous guinea
      pig smooth muscle cell PG release, which was due to increased COX-2 synthesis.

PMID- 15850714
TI  - Plasma fatty acids of neonates born to mothers with and without gestational
      diabetes.
AB  - Women with gestational diabetes mellitus (GDM) and their neonates have lower
      levels of arachidonic (AA) and docosahexaenoic (DHA) acids in red cell membranes.
      It is not clear if this abnormality is restricted to red cells or is a
      generalised problem. We have investigated plasma fatty acids of neonates (venous
      cord) of GDM (n=37), and non-diabetic (n=31) women. The GDMs had lower levels of
      dihomogamma-linolenic (20:3n-6, DHGLA) acid, summation operator n-6 metabolites,
      DHA and summation operator n-3 metabolites (p<0.05) in choline phosphoglycerides
      (CPG). They also had lower levels of AA (-4.5%), adrenic acid (22:4n-6, -13%),
      osbond acid (22:5n-6, -7%) and summation operator n-6 (-2.5%). There was a
      similar pattern in triglycerides (TG) and cholesterol esters (CE). Mead acid, a
      marker of generalised shortage of derived and parent essential fatty acids, was
      higher in CPG and TG of the GDM group by 73% and 76%. The adrenic/osbond acid
      (22:4n-6/22:5n-6) ratio, a biochemical marker of DHA insufficiency, was reduced
      in CPG (-4.5%), TG (-63%) and CE (-75%) of the GDM group. These findings, which
      are consistent with the previous red cell data, suggest that the neuro-visual and
      vascular development and function of the offspring of GDM women may be adversely
      affected if the levels of AA and DHA are compromised further by other factors,
      pre- or post-natally. Studies are required to elucidate the underlying mechanism
      for the reduction of the two fatty acids and to evaluate the developmental and
      health implications.

PMID- 15850715
TI  - A defect in the activity of Delta6 and Delta5 desaturases may be a factor
      predisposing to the development of insulin resistance syndrome.
AB  - GLUT-4 (glucose transporter) receptor, tumor necrosis factor-alpha (TNF-alpha),
      interleukins-6 (IL-6), daf-genes and PPARs (peroxisomal proliferation activator
      receptors) play a role in the development of insulin resistance syndrome and
      associated conditions. But, the exact interaction between these molecules/factors
      and the mechanism(s) by which they produce insulin resistance syndrome is not
      clear. I propose that a defect in the activity of the enzymes Delta6 and Delta5
      desaturases that are essential for the formation of long chain metabolites of
      essential fatty acids, linoleic acid and alpha-linolenic acid, is a factor in the
      development of insulin resistance syndrome. Long chain polyunsaturated fatty
      acids (LCPUFAs) increase cell membrane fluidity and enhance the number of insulin
      receptors and the affinity of insulin to its receptors; suppress TNF-alpha, IL-6,
      macrophage migration inhibitory factor (MIF) and leptin synthesis; increase the
      number of GLUT-4 receptors, serve as endogenous ligands of PPARs, modify
      lipolysis, and regulate the balance between pro- and anti-oxidants, and thus,
      play a critical role in the pathogenesis of insulin resistance. In the nematode,
      Caenorhabditis elegans, the protein encoded by daf-2 is 35% identical to the
      human insulin receptor; daf-7 codes a transforming growth factor-beta (TGF-beta)
      type signal and daf-16 enhances superoxide dismutase (SOD) expression. Melatonin
      has anti-oxidant actions similar to daf-16, TGF-beta and SOD. Calorie restriction
      enhances the activity of Delta6 and Delta5 desaturases, melatonin production,
      decreases daf-2 signaling, free radical generation, and augments anti-oxidant
      defenses that may explain the beneficial effect of diet control in the management
      of obesity, insulin resistance, and type II diabetes mellitus. These evidences
      suggest that the activities of Delta6 and Delta5 enzymes play a critical role in
      the expression and regulation of GLUT-4, TNF-alpha, IL-6, MIF, daf-genes,
      melatonin, and leptin by modulating the synthesis and tissue concentrations of
      LCPUFAs. Caloric restriction delays ageing by activating Sir 2 deacetylase in
      yeast, and expression of Sir 2 (SIRT1) in human cells. Both insulin and insulin
      like growth factor-1 (IGF-1) attenuated this response. SIRT1 sequesters the
      proapoptotic factor Bax, prevents stress-induced apoptosis of cells, and thus,
      prolongs survival. In addition, SIRT1 repressed PPAR-gamma, and overexpression of
      SIRT1 attenuated adipogenesis, and upregulation of SIRT in differentiated fat
      cells triggered lipolysis and loss of fat, events that are known to attenuate
      insulin resistance and prolong life span. It remains to be seen whether LCPUFAs
      have a regulatory role in SIRT1 expression and control Sir 2 deacetylase
      activity. Thus, calorie restriction or reduced food intake has a role not only in
      the pathobiology of insulin resistance, but also in other associated conditions
      such as obesity, type II diabetes mellitus, ageing, and longevity.

PMID- 15850716
TI  - Modulatory influence of sodium 2-propenyl thiosulfate from garlic on
      cyclooxygenase activity in canine platelets: possible mechanism for the anti
      aggregatory effect.
AB  - We previously found that sodium 2-propenyl thiosulfate (2PTS) has an anti
      aggregatory effect in vitro on both canine and human platelets at relatively low
      concentrations, but the extent of aggregation tends to return to the control
      level at high concentrations. To clarify the mechanism of this modulatory
      influence of 2PTS on the aggregation of platelets, we investigated the effects of
      2PTS on cyclooxygenase (COX) activity and the reduced glutathione (GSH)
      concentration in canine platelets. Platelet COX activity was inhibited by 2PTS in
      a dose-dependent manner up to 0.1 mM, but tended to return to the control level
      at 1 mM. In contrast, the platelet GSH concentration decreased in a dose
      dependent manner after treatment with 2PTS and a significant decrease was
      observed at 0.1 mM (P<0.05) and 1 mM (P<0.001). Furthermore, the activity of
      purified COX-1 was directly inhibited by addition of GSH in a dose-dependent
      manner. From these results, we conclude that the 2PTS-induced inhibition of
      platelet aggregation occurs as a result of inhibition of COX activity.
      Additionally, 2PTS may have a modulatory effect on platelet aggregation by
      affecting the platelet GSH concentration.

PMID- 15850717
TI  - N-6 polyunsaturated fatty acids confer hemodynamic stability in an experimental
      model of multiple trauma.
AB  - Immunonutrition with diets enriched in polyunsaturated fatty acids (PUFAs) are
      becoming mandatory for multiple trauma patients. Solutions containing single n-6
      PUFAs were administered intravenously in an experimental model of trauma. Thirty
      five rabbits were studied; 13 controls; 10 administered gamma-linolenic acid
      (GLA) 30 min after fracture of the right femor; and 12 arachidonic acid (AA).
      Systolic, diastolic and mean arterial pressures and heart rate were recorded;
      serum levels of tumor necrosis factor-alpha (TNFalpha), malondialdehyde (MDA) and
      nitrate were estimated before and after therapy. Mean survival of controls, of
      animals treated with GLA and of animals treated with AA was 0.80, 1.41 and 3.60
      days, respectively. Administration of PUFAs induced higher levels of blood
      pressure; that of AA decreased serum TNFalpha and tissue bacterial load compared
      to controls. Intravenous administration of n-6 PUFAs conferred hemodynamic
      stability and increased survival in a model of trauma rendering further research
      mandatory.

PMID- 15850718
TI  - 15-lipoxygenase metabolites of gamma-linolenic acid/eicosapentaenoic acid
      suppress growth and arachidonic acid metabolism in human prostatic adenocarcinoma
      cells: possible implications of dietary fatty acids.
AB  - Although gammalinolenic acid (GLA) and eicosapentaenoic acid (EPA) have
      independently been reported to suppress growth of cancer cells, their relative
      potencies are unknown. To determine the possible attenuating efficacies of
      dietary GLA or EPA on prostate carcinogenesis, we hereby report the in vitro
      effects of GLA, EPA and their 15-lipoxygenase (15-LOX) metabolites: 15(S)-HETrE
      and 15(S)-HEPE, respectively, on growth and arachidonic acid (AA) metabolism in
      human androgen-dependent (LNCaP) and androgen-independent (PC-3) prostatic cancer
      cells in culture. Specifically, both cells were preincubated respectively with
      the above PUFAs. Growth was determined by [3H]thymidine uptake and AA metabolism
      by HPLC analysis of the extracted metabolites. Our data revealed increased
      biosynthesis of prostaglandin E2 (PGE2) and 5-hydroxyeicosatetraenoic acid (5(S)
      HETE) by both cells. Preincubation of the cells with 15(S)-HETrE or 15(S)-HEPE
      more markedly inhibited cellular growth and AA metabolism when compared to
      precursor PUFAs. Notably, 15(S)-HETrE exerted the greatest inhibitory effects.
      These findings therefore imply that dietary GLA rather than EPA should better
      attenuate prostate carcinogenesis via its in vivo generation of 15(S)-HETrE, thus
      warranting exploration.

PMID- 15850719
TI  - Short-term changes in prostacyclin secretory profile of irradiated rat cervical
      spinal cord.
AB  - Prostaglandins changes in radiation myelopathy (RM) have been previously
      reported. In the present study, we decided to determine the profile of
      Prostacyclin (PGI2) content in irradiated rat cervical cord. Wistar rats were
      irradiated with doses of 2,4,6,15,25 and 30 Gy of X-rays. After 24 h, 2 and 13
      weeks post-irradiation, samples of spinal cord were prepared for evaluation of
      PGI2 and histopathologic changes. Prostacyclin content was determined by
      quantification of 6-keto-prostaglandin-F1alpha (prostacyclin major metabolite).
      Irradiated segments of spinal cord were stained routinely for histological
      studies. Results of irradiated were compared to control groups. Average ratio
      values of 6-keto-PG-F1alpha for doses of 2-30 Gy were between 67.5% and 107%,
      65.41% and 100.54%, and 62.20% and 98.89% for 24 h, 2 and 13 weeks post
      irradiation, respectively. Histopathological studies showed marked gliosis and
      vascularities in irradiated specimens. PGI2 bimodal secretory profile was
      observed along with histopathological changes in this study. Our results can
      further emphasize on the role of PGI2 in RM.

PMID- 15850720
TI  - Fluvastatin plus fish oil are more effective on cardiovascular risk factors than
      fluvastatin alone.

PMID- 15850721
TI  - Grey matter changes over time in high risk subjects developing schizophrenia.
AB  - Schizophrenia affects approximately 1% of the population and is associated with
      reductions in brain volume, but when these are first evident is unknown. Magnetic
      resonance imaging (MRI) has demonstrated abnormalities of brain structure,
      particularly of the temporal lobes, in schizophrenia. A study of brain structure
      in individuals destined to develop schizophrenia, before they do so, is crucial
      to understanding the illness. We used Voxel Based Morphometry (VBM) to map
      changes in Grey Matter Density (GMD) in 65 young adults at high risk of
      schizophrenia, for familial reasons, and 19 healthy young adults, over a period
      of approximately 2 years. All subjects were anti-psychotic naive at both scans.
      No increases in GMD were found in any of the groups. Within the high-risk group
      significant declines in GMD were found in the temporal lobes, the right frontal
      lobe and right parietal lobe. In the control group a decline was found in the
      right gyrus rectus. No significant differences over time were found between any
      of the groups. Those individuals at high risk who had transient or isolated
      psychotic symptoms showed a different spatial pattern of reductions in GMD than
      those who did not in within group comparisons. In addition, those individuals at
      high risk who later developed schizophrenia also showed a different spatial
      pattern of reductions in GMD in the left temporal lobe and right cerebellum, from
      2 to 3 years before they were diagnosed. These particular reductions may
      therefore be able to predict the later onset of schizophrenia.

PMID- 15850722
TI  - Functional MRI reveals the existence of modality and coordination-dependent
      timing networks.
AB  - Growing evidence suggests that interval timing in humans is supported by
      distributed brain networks. Recently, we demonstrated that the specific network
      recruited for the performance of rhythmic timing is not static but is influenced
      by the coordination pattern employed during interval acquisition. Here we expand
      on this previous work to investigate the role of stimulus modality and
      coordination pattern in determining the brain areas recruited for performance of
      a self-paced rhythmic timing task. Subjects were paced with either a visual or an
      auditory metronome in either a synchronized (on the beat) or syncopated (off the
      beat) coordination pattern. The pacing stimulus was then removed and subjects
      continued to move based on the required interval. When compared with networks
      recruited for auditory pacing and continuation, the visual-specific activity was
      observed in the classic dorsal visual stream that included bilateral MT/V5,
      bilateral superior parietal lobe, and right ventral premotor cortex. Activity in
      these regions was present not only during pacing, when visual information is used
      to guide motor behavior, but also during continuation, when visual information
      specifying the temporal interval was no longer present. These results suggest a
      role for modality-specific areas in processing and representing temporal
      information. The cognitive demands imposed by syncopated coordination resulted in
      increased activity in a broad network that included supplementary motor area,
      lateral pre-motor cortex, bilateral insula, and cerebellum. This coordination
      dependent activity persisted during the subsequent continuation period, when
      stimuli were removed and no coordination constraints were imposed. Taken
      together, the present results provide additional evidence that time and timing
      are served by a context-dependent distributed network rooted in basic
      sensorimotor processes.

PMID- 15850723
TI  - Spatial information is processed even when it is task-irrelevant: implications
      for neuroimaging task design.
AB  - Many neuroimaging studies have been designed to differentiate domain-specific
      processes in the brain. A common design constraint is to use identical stimuli
      for different domain-specific tasks. For example, an experiment investigating
      spatial versus identity processing would present compound spatial-identity
      stimuli in both spatial and identity tasks, and participants would be instructed
      to attend to, encode, maintain, or retrieve spatial information in the spatial
      task, and identity information in the identity task. An assumption in such
      studies is that spatial information will not be processed in the identity task,
      as it is irrelevant for that task. We report three experiments demonstrating
      violations of this assumption. Our results suggest that comparisons of spatial
      and identity tasks in existing neuroimaging studies have underestimated the
      amount of brain activation that is spatial-specific. For future neuroimaging
      studies, we recommend unique stimulus displays for each domain-specific task, and
      event-related measurement of post-stimulus processing.

PMID- 15850724
TI  - Localization bias and spatial resolution of adaptive and non-adaptive spatial
      filters for MEG source reconstruction.
AB  - This paper discusses the location bias and the spatial resolution in the
      reconstruction of a single dipole source by various spatial filtering techniques
      used for neuromagnetic imaging. We first analyze the location bias for several
      representative adaptive and non-adaptive spatial filters using their resolution
      kernels. This analysis theoretically validates previously reported empirical
      findings that standardized low-resolution electromagnetic tomography (sLORETA)
      has no location bias. We also find that the minimum-variance spatial filter does
      exhibit bias in the reconstructed location of a single source, but that this bias
      is eliminated by using the normalized lead field. We then focus on the comparison
      of sLORETA and the lead-field normalized minimum-variance spatial filter, and
      analyze the effect of noise on source location bias. We find that the signal-to
      noise ratio (SNR) in the measurements determines whether the sLORETA
      reconstruction has source location bias, while the lead-field normalized minimum
      variance spatial filter has no location bias even in the presence of noise.
      Finally, we compare the spatial resolution for sLORETA and the minimum-variance
      filter, and show that the minimum-variance filter attains much higher resolution
      than sLORETA does. The results of these analyses are validated by numerical
      experiments as well as by reconstructions based on two sets of evoked magnetic
      responses.

PMID- 15850725
TI  - Adults and children processing music: an fMRI study.
AB  - The present study investigates the functional neuroanatomy of music perception
      with functional magnetic resonance imaging (fMRI). Three different subject groups
      were investigated to examine developmental aspects and effects of musical
      training: 10-year-old children with varying degrees of musical training, adults
      without formal musical training (nonmusicians), and adult musicians. Subjects
      made judgements on sequences that ended on chords that were music-syntactically
      either regular or irregular. In adults, irregular chords activated the inferior
      frontal gyrus, orbital frontolateral cortex, the anterior insula, ventrolateral
      premotor cortex, anterior and posterior areas of the superior temporal gyrus, the
      superior temporal sulcus, and the supramarginal gyrus. These structures
      presumably form different networks mediating cognitive aspects of music
      processing (such as processing of musical syntax and musical meaning, as well as
      auditory working memory), and possibly emotional aspects of music processing. In
      the right hemisphere, the activation pattern of children was similar to that of
      adults. In the left hemisphere, adults showed larger activations than children in
      prefrontal areas, in the supramarginal gyrus, and in temporal areas. In both
      adults and children, musical training was correlated with stronger activations in
      the frontal operculum and the anterior portion of the superior temporal gyrus.

PMID- 15850726
TI  - Hippocampal shape analysis using medial surfaces.
AB  - In magnetic resonance imaging (MRI) research, significant attention has been paid
      to the analysis of the hippocampus (HC) within the medial temporal lobe because
      of its importance in memory and learning, and its role in neurodegenerative
      diseases. Manual segmentation protocols have established a volume decline in the
      HC in conjunction with Alzheimer's disease, epilepsy, post-traumatic stress
      disorder, and depression. Furthermore, recent studies have investigated age
      related changes of HC volume which show an interaction with gender; in early
      adulthood, volume reduction of the HC is found in men but not in women. In this
      paper, we investigated gender differences in normal subjects in young adulthood
      by employing a shape analysis of the HC using medial surfaces. For each subject,
      the most prominent medial manifold of the HC was extracted and flattened. The
      flattened sheets were then registered using both a rigid and a non-rigid
      alignment technique, and the medial surface radius was expressed as a height
      function over them. This allowed for an investigation of the association between
      subject variables and the local width of the HC. With regard to the effects of
      age and gender, it could be shown that the previously observed gender differences
      were mostly due to volume loss in males in the lateral areas of the HC head and
      tail. We suggest that the analysis of HC shape using medial surfaces might thus
      serve as a complimentary technique to investigate group differences to the
      established segmentation protocols for volume quantification in MRI.

PMID- 15850727
TI  - Differential generators for N20m and P35m responses to median nerve stimulation.
AB  - To study the spatial and behavioral dynamics of cortical sources for N20m and
      P35m at varying stimulus intensities, we measured neuromagnetic cortical
      responses to left electric median nerve stimulation at the wrist in 17 male
      healthy adults. The stimulus intensity levels were individually determined
      according to sensory threshold (ST) for perceiving electric pulses. Using
      equivalent current dipole (ECD) modeling, we analyzed the peak latencies,
      amplitudes, and locations of ECDs from 14 subjects for N20m and P35m elicited at
      2 ST, 3 ST, and 4 ST. Compared with N20m, P35m was localized 3.3 +/- 0.6 mm more
      superiorly at 2-4 ST, and 2.9 +/- 1.2 mm more medially at 3-4 ST. Superimposed
      over subjects' own MR images, N20m ECDs were localized in the area of 3b
      contralateral to stimulus side in all 17 subjects at 3 ST, whereas P35m ECDs were
      localized either in the postcentral (in 14 subjects) or in the precentral areas
      (in 3 subjects). We found no clear correlation between N20m and P35m in terms of
      peak latencies as well as the corresponding growth of activation strengths along
      with stepwise increase in stimulus intensity. Our results imply that the two
      early SEF components, N20m and P35m, have differential cortical generators, with
      distinctive neurophysiological behaviors in response to varying stimulus
      intensity levels.

PMID- 15850728
TI  - An arteriolar compliance model of the cerebral blood flow response to neural
      stimulus.
AB  - Although functional magnetic resonance imaging (fMRI) is a widely used and
      powerful tool for studying brain function, the quantitative interpretation of
      fMRI measurements for basic neuroscience and clinical studies can be complicated
      by inter-subject and inter-session variability arising from modulation of the
      baseline vascular state by disease, aging, diet, and pharmacological agents. In
      particular, recent studies have shown that the temporal dynamics of the cerebral
      blood flow (CBF) and the blood oxygenation level dependent (BOLD) responses to
      stimulus are modulated by changes in baseline CBF induced by various vasoactive
      agents and by decreases in vascular compliance associated with aging. These
      effects are not readily explained using current models of the CBF and BOLD
      responses. We present here a second-order nonlinear feedback model of the evoked
      CBF response in which neural activity modulates the compliance of arteriolar
      smooth muscle. Within this model framework, the baseline vascular state affects
      the dynamic response by changing the relative contributions of an active smooth
      muscle component and a passive connective tissue component to the overall vessel
      compliance. Baseline dependencies of the BOLD signal are studied by coupling the
      arteriolar compliance model with a previously described balloon model of the
      venous compartment. Numerical simulations show that the proposed model describes
      to first order the observed dependence of CBF and BOLD responses on the baseline
      vascular state.

PMID- 15850730
TI  - Parameter estimation in the magnitude-only and complex-valued fMRI data models.
AB  - In functional magnetic resonance imaging, voxel time courses are complex-valued
      data but are traditionally converted to real magnitude-only data ones. At a large
      signal-to-noise ratio (SNR), the magnitude-only data Ricean distribution is
      approximated by a normal distribution that has been suggested as reasonable in
      magnitude-only data magnetic resonance images for an SNR of 5 and potentially as
      low as 3. A complex activation model has been recently introduced by Rowe and
      Logan [Rowe, D.B., and Logan, B.R. (2004). A complex way to compute fMRI
      activation. NeuroImage, 23 (3):1078-1092] that is valid for all SNRs. The
      properties of the parameter estimators and activation statistic for these two
      models and a more accurate Ricean approximation based on a Taylor series
      expansion are characterized in terms of bias, variance, and Cramer-Rao lower
      bound. It was found that the unbiased estimators in the complex model continued
      to be unbiased for lower SNRs while those of the normal magnitude-only data model
      became biased as the SNR decreased and at differing levels for the regression
      coefficients. The unbiased parameter estimators from the approximate magnitude
      only Ricean Taylor model were unbiased to lower SNRs than the magnitude-only
      normal ones. Further, the variances of the parameter estimators achieved their
      minimum value in the complex data model regardless of SNR while the magnitude
      only data normal model and Ricean approximation using a Taylor series did not as
      the SNR decreased. Finally, the mean activation statistic for the complex data
      model was higher and not SNR dependent while it decreased with SNR in the
      magnitude-only data models but less so for the approximate Ricean model. These
      results indicate that using the complex data model and not approximations to the
      true magnitude-only Ricean data model is more appropriate at lower SNRs.
      Therefore, since the computational cost is relatively low for the complex data
      model and since the SNR is not inherently known a priori for all voxels, the
      complex data model is recommended at all SNRs.

PMID- 15850729
TI  - Stability of amygdala BOLD response to fearful faces over multiple scan sessions.
AB  - We used fMRI to examine amygdala activation in response to fearful facial
      expressions, measured over multiple scanning sessions. 15 human subjects
      underwent three scanning sessions, at 0, 2 and 8 weeks. During each session,
      functional brain images centered about the amygdala were acquired continuously
      while participants were shown alternating blocks of fearful, neutral and happy
      facial expressions. Intraclass correlation coefficients calculated across the
      sessions indicated stability of response in left amygdala to fearful faces (as a
      change from baseline), but considerably less left amygdala stability in responses
      to neutral expressions and for fear versus neutral contrasts. The results
      demonstrate that the measurement of fMRI BOLD responses in amygdala to fearful
      facial expressions might be usefully employed as an index of amygdala reactivity
      over extended periods. While signal change to fearful facial expressions appears
      robust, the experimental design employed here has yielded variable responsivity
      within baseline or comparison conditions. Future studies might manipulate the
      experimental design to either amplify or attenuate this variability, according to
      the goals of the research.

PMID- 15850731
TI  - Finger tapping, handedness and grey matter amount in the Rolando's genu area.
AB  - The morphology of the central sulcus (CS), at the level of the hand primary motor
      cortex, has been shown to be related to hand preference and skill. Differences in
      the cerebral functional organisation of left and right-handers have been
      described, notably with respect to hemispheric specialisation, which might cause
      the neural substrate of hand dominance or skill to differ between the two groups.
      Here, we further explored the relationship between the anatomical variability of
      the central sulcus and hand skill in two groups of young male subjects differing
      by handedness (n = 56 right-handers and n = 55 left-handers). Grey matter volume
      (GMV) in the upper region of the central sulcus was estimated with Voxel Based
      Morphometry, using a probabilistic region of interest approach, while hand motor
      skill was measured with the finger tapping test. No significant anatomical
      differences could be evidenced between the two hand preference groups, a
      rightward hemispheric asymmetry being observed in both samples. However, multiple
      regression analyses showed that, in the right-handed group, the maximum tapping
      rate of the right hand correlated positively with the left central sulcus GMV,
      but negatively with the right. Similar analyses showed that, in left-handers, the
      maximum tapping rate of the non-dominant right hand was strongly correlated with
      the GMV of the ipsilateral CS but not significantly with that of the
      contralateral CS. These results may be due to differences in the organisation of
      motor systems between these two groups, possibly concerning a left hemispheric
      specialisation for fast repetitive movements in right-handers, which would be
      different in left-handers.

PMID- 15850732
TI  - MRI-based surface-assisted parcellation of human cerebellar cortex: an
      anatomically specified method with estimate of reliability.
AB  - We revisit here a surface assisted parcellation (SAP) system of the human
      cerebellar cortex originally described in Makris, N., Hodge, S.M., Haselgrove,
      C., Kennedy, D.N., Dale, A., Fischl, B., Rosen, B.R., Harris, G., Caviness, V.S.,
      Jr., Schmahmann, J.D., 2003. Human cerebellum: surface-assisted cortical
      parcellation and volumetry with magnetic resonance imaging. J Cogn Neurosci 15,
      584-599. This system preserves the topographic and morphologic uniqueness of the
      individual cerebellum and allows for volumetric analysis and representation of
      multimodal structural and functional data on the cerebellar cortex. This
      methodology integrates features of automated routines of the program FreeSurfer
      as well as semi-automated and manual procedures of the program Cardviews to
      create 64 cerebellar parcellation units based on fissure information and
      anatomical landmarks of the cerebellar surface. Using this technique, we
      undertook the parcellation of ten cerebella by two independent raters. The
      reliability of the resulting parcellation units (64 total) was high, with an
      average Intraclass Correlation Coefficient (ICC) of 0.724 in the vermis and 0.853
      in the hemispheres. Clusters of parcellation units were then created, based on
      lobar and connectivity data and functional hypotheses. These 36 clusters, when
      treated as anatomical units, had an average ICC of 0.933. Whereas the individual
      units provide a high level of detail and anatomical specificity, the clusters add
      flexibility to the analysis by providing higher reliability.

PMID- 15850733
TI  - Expectancy and belief modulate the neuronal substrates of pain treated by
      acupuncture.
AB  - Both specific and non-specific factors may play a role in acupuncture therapy for
      pain. We explored the cerebral consequences of needling and expectation with real
      acupuncture, placebo acupuncture and skin-prick, using a single-blind, randomized
      crossover design with 14 patients suffering from painful osteoarthritis, who were
      scanned with positron emission tomography (PET). The three interventions, all of
      which were sub-optimal acupuncture treatment, did not modify the patient's pain.
      The insula ipsilateral to the site of needling was activated to a greater extent
      during real acupuncture than during the placebo intervention. Real acupuncture
      and placebo (with the same expectation of effect as real acupuncture) caused
      greater activation than skin prick (no expectation of a therapeutic effect) in
      the right dorsolateral prefrontal cortex, anterior cingulate cortex, and
      midbrain. These results suggest that real acupuncture has a specific
      physiological effect and that patients' expectation and belief regarding a
      potentially beneficial treatment modulate activity in component areas of the
      reward system.

PMID- 15850734
TI  - Perceptual bias following visual target selection.
AB  - Attending to a relevant item in a visual display is thought to require not only
      selective attention to this item, but also active inhibition of surrounding
      distractor items. As a consequence of this spatial inhibition, selection of a
      relevant item in a previous distractor location is slowed (i.e., the spatial
      inhibition effect). The goal of this study is to identify brain regions that are
      involved in this spatial inhibition effect using functional magnetic resonance
      imaging (fMRI). Subjects had to select a target from a display which also
      included a distractor, while that target was presented in either a new location
      (control) or in a location previously occupied by a distractor (spatial
      inhibition). A region of interest analysis revealed decreased activation in the
      superior parietal lobe (SPL), but increased activation in the motor areas
      (supplementary motor area, putamen) when the target was presented in a previously
      inhibited compared to a new location. We take these results to suggest that
      presenting a target in a previously inhibited location negatively biases the
      selection of that target in favor of an accompanying distractor. This may result
      in an initially more efficient selection process, resulting in lower activation
      in the SPL. Counteracting this perceptual bias possibly requires additional motor
      activation. This study provides evidence for the notion that to make selection
      more efficient, prior information concerning an item is used. When this prior
      information conflicts with the current stimulus demands, compensatory motor
      actions are taken to correct this perceptual bias.

PMID- 15850735
TI  - Voxel-based morphometry and stereology provide convergent evidence of the
      importance of medial prefrontal cortex for fluid intelligence in healthy adults.
AB  - We investigated whether a relationship exists between frontal lobe volume and
      fluid intelligence as measured by both Cattell's Culture Fair test and the
      Wechsler Adult Intelligence Scale-Revised (WAIS-R) Performance scale, but not
      with crystallized intelligence as measured by the WAIS-R Verbal scale, in healthy
      adults, using two well-established image analysis techniques applied to high
      resolution MR brain images. Firstly, using voxel-based morphometry (VBM), we
      investigated whether a significant relationship exists between gray matter
      concentration and fluid intelligence on a voxel-by-voxel basis. Secondly, we
      applied the Cavalieri method of modern design stereology in combination with
      point counting to investigate possible relationships between macroscopic volumes
      of relevant brain regions defined as dorsolateral, dorsomedial, orbitolateral,
      and orbitomedial prefrontal cortex on the basis of neuroanatomical landmarks, and
      fluid intelligence. We also examined the effect on these relationships of
      normalizing regional brain volumes to intracranial volume. VBM analysis revealed
      a positive correlation between gray matter concentration in the medial region of
      prefrontal cortex and Culture Fair scores (corrected for multiple comparisons),
      and also WAIS-R Performance Intelligence sum of scaled scores (SSS) (uncorrected
      for multiple comparisons before controlling for age, and this converges with the
      stereological finding of the positive correlation between volume of dorsomedial
      prefrontal cortex normalized to intracranial volume and Culture Fair scores after
      controlling for age. WAIS-R Verbal Intelligence SSS showed no correlations. We
      interpret our findings, from independent analyses of both VBM and stereology, as
      evidence of the importance of medial prefrontal cortex in supporting fluid
      intelligence.

PMID- 15850736
TI  - Trial pacing in mental rotation tasks.
AB  - Functional imaging of mental rotation has revealed a wide variety of cortical
      activation patterns besides the consensus on parietal involvement. Some insight
      has been gained on the role of motor cortex, but the differential activation of
      other brain regions has received little attention. A previous fMRI study using a
      blocked substraction design [D'Esposito et al., NeuroImage 6 (1997) 113-121] has
      shown an effect of trial pacing on the observed activation pattern of a simple
      visuospatial task requiring mental rotation. In this study, we want to assess if
      trial pacing can help clarify some of the diversity in the observed cortical
      activation patterns associated with fMRI blocked designs of mental rotation so
      far, especially when comparing mental rotation of different stimuli. We used two
      different stimuli, i.e. hands and tools, that have been used in previous mental
      rotation studies. Our results revealed a bilateral involvement of lateral
      premotor and parietal cortex irrespective of trial pacing, but there was a marked
      influence of trial pacing on the observed activation of occipital and other
      frontal regions. Stimulus type specific activation patterns were entirely limited
      to the fixed-paced design. We conclude that trial pacing is a vital aspect when
      developing and interpreting the related imaging results of a blocked subtraction
      design. Fixed-paced designs may be more sensitive for duration effects. A self
      paced trial schedule may be more appropriate to isolate the neural substrate of
      the cognitive component of interest or to exclude response time differences as a
      confounding factor.

PMID- 15850737
TI  - Frontal and limbic metabolic differences in subjects selected according to
      genetic variation of the SLC6A4 gene polymorphism.
AB  - Allelic variants in the promoter region of the serotonin transporter (5-HTT) gene
      have been implicated in several psychiatric disorders and personality traits. In
      particular, two common alleles in a variable repeat sequence of the promoter
      region (SLC6A4) have been differentially associated with a display of abnormal
      levels of anxiety and affective illness in individuals carrying the "s" allele.
      The aim of this study was to compare the basal cerebral metabolic activity of non
      psychiatric subjects in fronto-limbic structures to determine whether differences
      exist in basal metabolic activity within this functional polymorphism. PET scans
      with fluorine-18 fluorodeoxyglucose as radiotracer were performed in 71 non
      psychiatric subjects previously screened for psychopathology and subsequently
      genotyped for SLC6A4; PET images were compared with SPM2 according to s/s (n =
      27), s/l (n = 25), and l/l (n = 19) groups considering a significance threshold
      in a priori selected areas of P < 0.001 and an extent threshold > or =5 voxels.
      The analysis showed an effect of interest among the three genotype groups in
      right anterior cingulate gyrus (ACC), left middle frontal gyrus, and left
      posterior cingulate gyrus (PCC). Comparison between l/l vs. s/s showed increased
      metabolism for l/l in left middle frontal gyrus and an increase for s/s in right
      ACC and left PCC. Comparison between s/s vs. s/l showed an increase for s/s in
      left PCC and right ACC. Increased basal metabolism in fronto-limbic structures
      for the s/s group may be conceived as an "overactive metabolic state" of these
      structures, possibly related to an increased susceptibility for developing an
      anxiety-depression spectrum disorder.

PMID- 15850738
TI  - Diffusion MR imaging characteristics of the developing primate brain.
AB  - Diffusion-based magnetic resonance imaging holds the potential to non-invasively
      demonstrate cellular-scale structural properties of brain. This method was
      applied to fixed baboon brains ranging from 90 to 185 days gestational age to
      characterize the changes in diffusion properties associated with brain
      development. Within each image voxel, a probability-theory-based approach was
      employed to choose, from a group of analytic equations, the one that best
      expressed water displacements. The resulting expressions contain eight or fewer
      adjustable parameters, indicating that relatively simple expressions are
      sufficient to obtain a complete description of the diffusion MRI signal in
      developing brain. The measured diffusion parameters changed systematically with
      gestational age, reflecting the rich underlying microstructural changes that take
      place during this developmental period. These changes closely parallel those of
      live, developing human brain. The information obtained from this primate model of
      cerebral microstructure is directly applicable to studies of human development.

PMID- 15850739
TI  - Brain mechanisms for mood congruent memory facilitation.
AB  - Emotional information is better remembered when mood at the time of retrieval
      matches it in valence (positive mood, positive material). An associative memory
      model predicts that this 'mood congruent' facilitation is due to the mood-related
      reactivation at retrieval of emotional responses which were linked to valenced
      information at encoding. To test this model, we presented subjects with positive
      and negative words at study and manipulated their mood at test while using
      functional imaging to monitor brain activity. Subjective mood ratings and heart
      rate variability both indicated that the manipulation was effective, and memory
      performance showed a strong trend towards facilitation in congruent conditions.
      In the functional imaging data, valence-specific conjunctions between encoding
      activity predicting subsequent memory in a congruent mood and retrieval activity
      relating to mood congruent recollection revealed shared responses in subgenual
      cingulate for positive valence and posteriolateral orbitofrontal cortex for
      negative valence, thus supporting the associative model. To elucidate the
      mnemonic basis of facilitation, independent of valence, we examined the shared
      correlates of positive and negative congruence and found that parts of the
      episodic memory system were activated by congruence in correct rejection trials,
      but no part of this system was activated by congruence in correctly remembered
      trials. This pattern suggests that mood congruent facilitation occurs at the
      level of attempted recall rather than that of successful recollection.

PMID- 15850740
TI  - Hippocampal activations during encoding and retrieval in a verbal working memory
      paradigm.
AB  - Though the hippocampus has been associated with encoding and retrieval processes
      in episodic memory, the precise nature of its involvement in working memory has
      yet to be determined. This functional magnetic resonance imaging (fMRI) study
      employed a verbal working memory paradigm that allows for the within-subject
      comparison of functional activations during encoding, maintenance, and retrieval.
      In each trial, participants were shown 5 target words and, after an 8 s delay, a
      series of probe words. Probe words consisted of target matches, phonetically or
      semantically related foils, or foils unrelated to the target words. Both the left
      and right hippocampi showed higher mean activation amplitudes during encoding
      than maintenance. In contrast, the right dorsolateral prefrontal cortex (DLPFC)
      showed greater activation during maintenance than encoding. Both hippocampal and
      DLPFC regions were more active during retrieval than maintenance. Furthermore, an
      analysis of retrieval activation separated by probe type showed a trend toward
      greater bilateral hippocampal activation for probes related (both semantically
      and phonetically) to the target than for unrelated probes and still greater
      activation for target matches. This pattern suggests that there may be roles for
      the hippocampus and DLPFC in working memory that change as function of
      information processing stage. Additionally, the trend towards increased
      involvement of the hippocampus with the increase in relatedness of the probe
      stimuli to the information maintained is interpreted to be consistent with the
      role of the hippocampus in recollection-based retrieval in long-term memory and
      may indicate that this role extends to working memory processes.

PMID- 15850741
TI  - Source analysis of interictal spikes in polymicrogyria: loss of relevant cortical
      fissures requires simultaneous EEG to avoid MEG misinterpretation.
AB  - PURPOSE: Multiple source analysis of interictal EEG and MEG spikes was used to
      identify irritative zones in polymicrogyria (PMG). Spike onset times and source
      localization were compared between both modalities. PMG is characterized by a
      marked loss of deep cortical fissures. Hence, differences between EEG and MEG
      were expected since MEG signals are predominantly generated from tangentially
      orientated neurons in fissures. PATIENTS: We studied 7 children and young adults
      (age 7.5 to 19 years) with localization-related epilepsy and unilateral
      polymicrogyria (PMG) as defined from anatomical MRI. METHODS: 122-channel whole
      head MEG and 32-channel EEG were recorded simultaneously for 25 to 40 min. Using
      the BESA program, interictal spikes were identified visually and used as
      templates to search for similar spatio-temporal spike patterns throughout the
      recording. Detected similar spikes (r > 0.85) were averaged, high-pass filtered
      (5 Hz) to enhance spike onset, and subjected to multiple spatio-temporal source
      analysis. Source localization was visualized by superposition on T1-weighted MRI
      and compared to the lesion. RESULTS: Nine spike types were identified in seven
      patients (2 types in 2 patients). Eight out of nine EEG sources and seven MEG
      sources modeling spike onset were localized within the visible lesion. EEG spike
      onset preceded MEG significantly in two spike types by 19 and 25 ms. This was
      related to radial onset activity in EEG while MEG localized propagated activity.
      In one case, the earliest MEG spike activity was localized to the normal
      hemisphere while the preceding radial EEG onset activity was localized within the
      lesion. Distances between EEG and MEG onset sources varied markedly between 9 and
      51 mm in the eight spike types with concordant lateralization. CONCLUSION:
      Interictal irritative zones were localized within the lesion in PMG comparable to
      other malformations, e.g., FCD. Discrepancies in MEG and EEG were related to the
      lack of deep fissures in PMG. In two cases, MEG was blind to the onset of radial
      interictal spike activity and localized propagated spike activity. In two other
      cases, MEG localized to the more peripheral parts of the irritative zone.
      Simultaneous EEG recordings with MEG and multiple source analysis are required to
      avoid problems of MEG interpretation.

PMID- 15850742
TI  - Spatiotemporal properties of the BOLD response in the songbirds' auditory circuit
      during a variety of listening tasks.
AB  - Auditory fMRI in humans has recently received increasing attention from cognitive
      neuroscientists as a tool to understand mental processing of learned acoustic
      sequences and analyzing speech recognition and development of musical skills. The
      present study introduces this tool in a well-documented animal model for vocal
      learning, the songbird, and provides fundamental insight in the main technical
      issues associated with auditory fMRI in these songbirds. Stimulation protocols
      with various listening tasks lead to appropriate activation of successive relays
      in the songbirds' auditory pathway. The elicited BOLD response is also region and
      stimulus specific, and its temporal aspects provide accurate measures of the
      changes in brain physiology induced by the acoustic stimuli. Extensive repetition
      of an identical stimulus does not lead to habituation of the response in the
      primary or secondary telencephalic auditory regions of anesthetized subjects. The
      BOLD signal intensity changes during a stimulation and subsequent rest period
      have a very specific time course which shows a remarkable resemblance to auditory
      evoked BOLD responses commonly observed in human subjects. This observation
      indicates that auditory fMRI in the songbird may establish a link between
      auditory related neuro-imaging studies done in humans and the large body of neuro
      ethological research on song learning and neuro-plasticity performed in
      songbirds.

PMID- 15850743
TI  - Cortical thickness analysis in autism with heat kernel smoothing.
AB  - We present a novel data smoothing and analysis framework for cortical thickness
      data defined on the brain cortical manifold. Gaussian kernel smoothing, which
      weights neighboring observations according to their 3D Euclidean distance, has
      been widely used in 3D brain images to increase the signal-to-noise ratio. When
      the observations lie on a convoluted brain surface, however, it is more natural
      to assign the weights based on the geodesic distance along the surface. We
      therefore develop a framework for geodesic distance-based kernel smoothing and
      statistical analysis on the cortical manifolds. As an illustration, we apply our
      methods in detecting the regions of abnormal cortical thickness in 16 high
      functioning autistic children via random field based multiple comparison
      correction that utilizes the new smoothing technique.

PMID- 15850744
TI  - Imaging brain connectivity in children with diverse reading ability.
AB  - Reading is a complex cognitive skill that requires the coordination of multiple
      brain regions. Although functional neuroimaging studies highlight the cortical
      brain regions associated with a specific cognitive task like reading, they do not
      directly address the underlying neural connections necessary for efficient
      performance of this task. Adults with reading disability have demonstrated lower
      regional white matter connectivity, but it is not known whether this relationship
      between neuronal wiring and reading performance also holds in younger readers.
      Using diffusion tensor magnetic resonance imaging (DTI) that highlights the
      structural integrity of the brain wiring, we show that regional brain
      connectivity in the left temporo-parietal white matter correlates with a wide
      range of reading ability in children as young as 8-12 years old. Diffusion tensor
      tractography suggests that the posterior limb of the internal capsule is
      consistent with the location of the largest cluster of correlation between
      reading ability (Word Identification subtest) and fractional anisotropy. The
      maturation of the white matter may play a key role in the development of
      cognitive processes such as reading.

PMID- 15850745
TI  - Local magnetization transfer ratio signal inhomogeneity is related to subsequent
      change in MTR in lesions and normal-appearing white-matter of multiple sclerosis
      patients.
AB  - Multiple sclerosis (MS) lesions show differing degrees of demyelination and
      remyelination. Changes in myelin content are associated with changes in
      magnetization transfer on MRI. Since acute inflammation and demyelination are
      spatially and temporally inhomogeneous, we hypothesized that local magnetic
      transfer ratio (MTR) heterogeneity might be predictive of subsequent changes in
      MTR. To test this hypothesis, we analyzed MTR images obtained in 14 subjects, at
      baseline and after 2 months follow-up. We segmented lesions and normal-appearing
      white-matter (NAWM), calculated MTR signal inhomogeneity maps at baseline and MTR
      lesion difference maps between baseline and follow-up. We found that regions with
      low MTR inhomogeneity at baseline experienced little further change in MTR on
      follow-up. The mean change in lesion MTR between baseline and follow-up was 0.10
      +/- 3.70; in NAWM it was -0.09 +/- 2.02. We found that regions with high MTR
      inhomogeneity at baseline would change MTR on follow-up: (1) voxels with
      significantly high MTR in regions of high MTR inhomogeneity at baseline showed a
      mean decrease in MTR between baseline and follow-up of -2.51 +/- 4.68 in lesions
      and -1.41 +/- 3.00 in NAWM; (2) voxels with low MTR in regions of high MTR
      inhomogeneity at baseline showed a mean increase in MTR between baseline and
      follow-up of 2.61 +/- 6.07 in lesions. These changes in MTR were significantly
      different (P < 0.001). These results suggest that calculation of MTR signal
      inhomogeneity may provide a method for quantifying the potential for
      remyelination and demyelination, and thus could provide an important MRI
      biomarker for assessing the efficacy of therapies targeting remyelination.

PMID- 15850746
TI  - Amygdala and nucleus accumbens in responses to receipt and omission of gains in
      adults and adolescents.
AB  - Adolescents' propensity for risk-taking and reward-seeking behaviors suggests a
      heightened sensitivity for reward, reflected by greater feedback-related activity
      changes in reward circuitry (e.g., nucleus accumbens), and/or a lower sensitivity
      to potential harm reflected by weaker feedback-related activity changes in
      avoidance circuitry (e.g., amygdala) relative to adults. Responses of nucleus
      accumbens and amygdala to valenced outcomes (reward receipt and reward omission)
      were assayed using an event-related functional magnetic resonance imaging
      procedure paired with a monetary reward task in 14 adults and 16 adolescents.
      Bilateral amygdala and nucleus accumbens showed significantly greater activation
      when winning than when failing to win in both groups. Group comparisons revealed
      stronger activation of left nucleus accumbens by adolescents, and of left
      amygdala by adults. When examining responses to reward receipts and to reward
      omissions separately, the most robust group difference was within the amygdala
      during reward omission. The reduction of the fMRI BOLD signal in the amygdala in
      response to reward omission was larger for adults than for adolescents.
      Correlations showed a close link between negative emotion and amygdala decreased
      BOLD signal in adults, and between positive emotion and nucleus accumbens
      activation in adolescents. Overall, these findings support the notion that the
      signal differences between positive and negative outcomes involve the nucleus
      accumbens more in adolescents than in adults, and the amygdala more in adults
      than in adolescents. These developmental differences, if replicated, may have
      important implications for the development of early-onset disorders of emotion
      and motivation.

PMID- 15850747
TI  - Functional representation of the finger and face in the human somatosensory
      cortex: intraoperative intrinsic optical imaging.
AB  - We applied the intrinsic optical imaging technique to the human primary
      somatosensory cortex during brain tumor/epilepsy surgery for nine patients. The
      cortical surface was illuminated with a Xenon light through an operating
      microscope, and the reflected light, which passed through a 605 nm bandpass
      filter, was detected by a CCD camera-based optical imaging system. Individual
      electrical stimulation of five digits induced changes in the reflected light
      intensities. Visualizing the intrinsic optical responses, we constructed maps of
      finger representation in Brodmann's area 1. In the maps, response areas of Digits
      I to V were sequentially aligned along the central sulcus in the crown of the
      postcentral gyrus from the latero-inferior region (Digit I) to the medio-superior
      region (Digit V). The neighboring response areas partially overlapped each other,
      as previously described in the monkey somatosensory cortex. Similar results were
      obtained in the face region with stimulation of the three branches of the
      trigeminal nerve. These results suggest that the overlap of the response areas is
      a common feature in the somatosensory cortex not only in monkeys, but also in
      humans.

PMID- 15850748
TI  - Modeling both the magnitude and phase of complex-valued fMRI data.
AB  - In MRI and fMRI, images or voxel measurement are complex valued or bivariate at
      each time point. Recently, (Rowe, D.B., Logan, B.R., 2004. A complex way to
      compute fMRI activation. NeuroImage 23 (3), 1078-1092) introduced an fMRI
      magnitude activation model that utilized both the real and imaginary data in each
      voxel. This model, following traditional beliefs, specified that the phase time
      course were fixed unknown quantities which may be estimated voxel-by-voxel.
      Subsequently, (Rowe, D.B., Logan, B.R., 2005. Complex fMRI analysis with
      unrestricted phase is equivalent to a magnitude-only model. NeuroImage 24 (2),
      603-606) generalized the model to have no restrictions on the phase time course.
      They showed that this unrestricted phase model was mathematically equivalent to
      the usual magnitude-only data model including regression coefficients and voxel
      activation statistic but philosophically different due to it derivation from
      complex data. Recent findings by (Hoogenrad, F.G., Reichenbach, J.R., Haacke,
      E.M., Lai, S., Kuppusamy, K., Sprenger, M., 1998. In vivo measurement of changes
      in venous blood-oxygenation with high resolution functional MRI at .95 Tesla by
      measuring changes in susceptibility and velocity. Magn. Reson. Med. 39 (1), 97
      107) and (Menon, R.S., 2002. Postacquisition suppression of large-vessel BOLD
      signals in high-resolution fMRI. Magn. Reson. Med. 47 (1), 1-9) indicate that the
      voxel phase time course may exhibit task related changes. In this paper, a
      general complex fMRI activation model is introduced that describes both the
      magnitude and phase in complex data which can be used to specifically
      characterize task related change in both. Hypotheses regarding task related
      magnitude and/or phase changes are evaluated using derived activation statistics.
      It was found that the Rowe-Logan complex constant phase model strongly biases
      against voxels with task related phase changes and that the current very general
      complex linear phase model can be cast to address several different hypotheses
      sensitive to different magnitude/phase changes.

PMID- 15850749
TI  - A new SPM toolbox for combining probabilistic cytoarchitectonic maps and
      functional imaging data.
AB  - Correlating the activation foci identified in functional imaging studies of the
      human brain with structural (e.g., cytoarchitectonic) information on the
      activated areas is a major methodological challenge for neuroscience research. We
      here present a new approach to make use of three-dimensional probabilistic
      cytoarchitectonic maps, as obtained from the analysis of human post-mortem
      brains, for correlating microscopical, anatomical and functional imaging data of
      the cerebral cortex. We introduce a new, MATLAB based toolbox for the SPM2
      software package which enables the integration of probabilistic cytoarchitectonic
      maps and results of functional imaging studies. The toolbox includes the
      functionality for the construction of summary maps combining probability of
      several cortical areas by finding the most probable assignment of each voxel to
      one of these areas. Its main feature is to provide several measures defining the
      degree of correspondence between architectonic areas and functional foci. The
      software, together with the presently available probability maps, is available as
      open source software to the neuroimaging community. This new toolbox provides an
      easy-to-use tool for the integrated analysis of functional and anatomical data in
      a common reference space.

PMID- 15850750
TI  - Sex differences in the neural correlates of child facial resemblance: an event
      related fMRI study.
AB  - Detection of genetic relatedness (i.e. kinship) impacts the social, parental, and
      sexual behavior of many species. In humans, self-referent phenotype matching
      based on facial resemblance may indicate kinship. For example, faces that
      resemble ours are perceived as more trustworthy and attractive. Sex differences
      in behavioral reactions to facial resemblance among children have also been
      demonstrated and are consistent with evolutionary theory suggesting that
      resemblance might serve as a paternity cue. Using event-related fMRI, we show
      that specific regions of the brain are implicated in processing facial
      resemblance and a sex difference in cortical response to facial resemblance
      expressed in children. We found a consistent activation in the fusiform gyrus
      across all face conditions, which is consistent with previous research on face
      processing. There were no sex differences in overall response to faces in the
      fusiform gyrus, and also to faces that did not resemble subjects. When
      resemblance was not modeled, females showed greater activation to child faces
      than males. Consistent with parental investment theory and theories of sexual
      selection, males showed greater cortical activity than females in response to
      children's faces that resembled them. These data suggest natural selection may
      have crafted a sexually differentiated neuro-sensory module implicated in
      detection of facial resemblance that may serve as a kin detection and paternity
      cue. This process may capitalize on neural substrates involved in self-referent
      processing and familiarity detection.

PMID- 15850751
TI  - Mycobacterium tuberculosis lineage: a naming of the parts.
AB  - There have been many reports of groups of related Mycobacterium tuberculosis
      strains described variously as lineages, families or clades. There is no
      objective definition of these groupings, making it impossible to define
      relationships between those groups with biological advantages. Here we describe
      two groups of related strains obtained from an epidemiological study in Tanzania,
      which we define as the Kilimanjaro and Meru lineages on the basis of IS6110
      restriction fragment length polymorphism (RFLP), polymorphic GC rich sequence
      (PGRS) RFLP and mycobacterial interspersed repeat unit (MIRU) typing. We
      investigated the concordance between each of the typing techniques and the
      dispersal of the typing profiles from a core pattern. The Meru lineage is more
      dispersed than the Kilimanjaro lineage and we speculate that the Meru lineage is
      older. We suggest that this approach provides an objective definition that proves
      robust in this epidemiological study. Such a framework will permit associations
      between a lineage and clinical or bacterial phenomenon to be tested objectively.
      This definition will also enable new putative lineages to be objectively tested.

PMID- 15850752
TI  - Sensitivity of human gamma interferon assay and tuberculin skin testing for
      detecting infection with Mycobacterium tuberculosis in patients with culture
      positive tuberculosis.
AB  - SETTING: Nine university-affiliated chest clinics in Australia. OBJECTIVE: To
      evaluate the sensitivity of a whole blood human gamma-interferon assay (HGIA,
      QuantiFERON-TB) for specific T lymphocyte responses and Tuberculin skin testing
      (TST) for the detection of Mycobacterium tuberculosis infection in subjects with
      culture-proven M. tuberculosis disease (TBCP). DESIGN: Prospective testing of 129
      patients with recent TBCP and 100 patients with non-tuberculosis lung disease
      (NTBLD). RESULTS: Using a defined level of specific IFN-gamma production and TST
      10mm as positive cut-offs, the sensitivity of HGIA was 81% compared to 89% for
      TST (p=0.06). When positive responses in both TST and HGIA were combined, 96% of
      TB patients were detected. For the NTBLD group, 43% of whom were born overseas,
      73% were negative for both the HGIA and TST. Prior immunization with M. bovis
      (bacille Calmette-Guerin) (BCG) or the type of TB had no effect on the
      sensitivities of the assays. For those treated for <2 months, the sensitivities
      for both assays were 84%, but for those treated for >2 months the sensitivity of
      TST (90%) tended to be higher than for HGIA (81%) (p=0.07). The distribution of
      TST results in TB patients showed a broad peak between 10 and 25 mm, while the
      results in the HGIA were bimodal in both TB and NTBLD patients. CONCLUSION: HGIA
      may prove an alternative to skin testing for detecting M. tuberculosis infection
      in certain settings.

PMID- 15850753
TI  - Mycobacterium avium enters a state of metabolic dormancy in response to
      starvation.
AB  - Members of the Mycobacterium avium complex (MAC) exhibit a highly effective and
      biphasic response to starvation, losing less than 90% viability after 2 years in
      deionized water. During the first adaptive phase of 4-7 days, the bacilli exhibit
      a burst of lipid catabolism, alteration of mycolate modifications, loss of
      catalase and urease activities, and a decline in sensitivity to antibiotics.
      There is also a decline in the protein level of alanine tRNA synthetase (AlaS),
      and an increase in ribonuclease E (Rne) levels. During the following persistence
      phase, the bacilli become metabolically dormant. However, with return of
      nutrients, the cells rapidly respond with increased activity, as determined by
      reduction of a tetrazolium dye. The primary reservoir for MAC is natural and
      municipal water, and the metabolic dormancy may be analogous to that of other
      aquatic organisms, such as vibrio. The organized metabolic shutdown that
      environmental mycobacteria utilize to survive starvation may have evolved into
      the host-specific dormancy mechanisms of Mycobacterium tuberculosis.

PMID- 15850754
TI  - Cell wall lipids from Mycobacterium bovis BCG are inflammatory when inoculated
      within a gel matrix: characterization of a new model of the granulomatous
      response to mycobacterial components.
AB  - The chronic inflammatory response to Mycobacterium generates complex
      granulomatous lesions that balance containment with destruction of infected
      tissues. To study the contributing factors from host and pathogen, we developed a
      model wherein defined mycobacterial components and leukocytes are delivered in a
      gel, eliciting a localized response that can be retrieved and analysed. We
      validated the model by comparing responses to the cell wall lipids from
      Mycobacterium bovis bacillus Calmette-Guerin (BCG) to reported activities in
      other models. BCG lipid-coated beads and bone marrow-derived macrophages (input
      macrophages) were injected intraperitoneally into BALB/c mice. Input macrophages
      and recruited peritoneal exudate cells took up fluorescently tagged BCG lipids,
      and matrix-associated macrophages and neutrophils produced tumor necrosis factor,
      interleukin-1alpha, and interleukin-6. Leukocyte numbers and cytokine levels were
      greater in BCG lipid-bearing matrices than matrices containing non-coated or
      phosphatidylglycerol-coated beads. Leukocytes arrived in successive waves of
      neutrophils, macrophages and eosinophils, followed by NK and T cells (CD4(+),
      CD8(+), or gammadelta) at 7 days and B cells within 12 days. BCG lipids also
      predisposed matrices for adherence and vascularization, enhancing cellular
      recruitment. We submit that the matrix model presents pertinent features of the
      murine granulomatous response that will prove to be an adaptable method for study
      of this complex response.

PMID- 15850755
TI  - An assay to compare the infectivity of Mycobacterium tuberculosis isolates based
      on aerosol infection of guinea pigs and assessment of bacteriology.
AB  - The aim of this study was to establish an assay to compare Mycobacterium
      tuberculosis strains, and cells grown under different growth conditions, in terms
      of their ability to cause a lung infection and disseminate to the spleen. M.
      tuberculosis strains H37Rv, Erdman, South Indian (TMC120, SI) and H37Rv cells
      grown aerobically or under low oxygen/iron limitation in a chemostat were assayed
      for infectivity. Groups of 8 animals were challenged with 3 different doses of
      each strain. Lung and spleen bacteriology was assessed at 16 days post-infection
      for all strains. Bacteriology and lung pathology at day 56 was studied for H37Rv,
      Erdman and SI. Strains H37Rv and Erdman had a statistically significantly higher
      pathogenic potential than SI and this was confirmed by analysis of lung pathology
      performed at 8 weeks post-infection, although the Erdman strain caused more
      extensive caseation without calcification and little encapsulation. The model
      could discriminate between cells grown under different growth conditions; low
      oxygen/iron-limited cells had a significantly higher infectivity than those grown
      aerobically. This study presents a quick and reliable method for comparing with
      statistical confidence, the pathogenic potential of M. tuberculosis strains and
      the impact of in vitro growth conditions on the infectivity of M. tuberculosis in
      vivo.

PMID- 15850757
TI  - HemZ is essential for heme biosynthesis in Mycobacterium tuberculosis.
AB  - The complete sequence and subsequent annotation of the Mycobacterium tuberculosis
      genome has allowed the prediction of many genes and gene functions by homology.
      HemZ is a predicted ferrochelatase which lies in an apparent operon with two
      genes involved in mycolic acid biosynthesis, mabA and inhA. We tried to construct
      hemZ deletion mutants in M. tuberculosis using a two-step recombination strategy,
      but could only delete the chromosomal copy when we provided a second functional
      copy on an integrating plasmid. We further confirmed that hemZ is essential under
      normal culture conditions by demonstrating that the integrated copy of hemZ could
      not be removed if it was the only wild-type allele in the cell. We were able to
      obtain hemZ mutants by supplementation with hemin but not with protoporphyrin IX
      or hemoglobin confirming that this gene does have a role in heme biosynthesis and
      that M. tuberculosis can transport hemin intracelullarly. The hemin auxotroph
      required 2 mug/ml hemin for growth and rapid loss of viability occurred after
      withdrawal of hemin. These data confirm the role of hemZ in heme biosynthesis and
      indicate that heme is an essential requirement for M. tuberculosis.

PMID- 15850756
TI  - Chemokine receptor 5 and its ligands in the immune response to murine
      tuberculosis.
AB  - SETTING: The ability of chemokines such as macrophage inflammatory protein (MIP)
      1alpha, MIP-1beta, and regulated-upon-activation, normal T cell expressed and
      secreted (RANTES), to attract and activate T cells and monocytes, the building
      blocks of the granuloma, suggests that these chemokines may have a role in
      modulating immune responses to Mycobacterium tuberculosis infection. OBJECTIVE:
      We hypothesized that the chemokine receptor 5 (CCR5) ligands, MIP-1alpha, MIP
      1beta and RANTES, are virulence correlates in M. tuberculosis infection and are
      indispensable to granuloma formation. DESIGN: The ability of virulent (H37Rv) and
      avirulent (H37Ra) strains of M. tuberculosis to induce chemokine production in
      vivo and in vitro was determined at protein and mRNA levels. We also compared
      bacterial burden, and granuloma numbers and size in H37Rv-infected CCR5-/- or
      wild-type C57BL/6 mice. RESULTS: In vivo, lung mRNA and protein measurements of
      MIP-1alpha, MIP-1beta and RANTES indicate significantly higher (p<0.05) values
      (days 14-28) in the H37Rv-infected than the H37Ra-infected mice. This is
      consistent with a higher infection burden of the virulent strain. However, in
      vitro alveolar macrophage stimulation by H37Rv or H37Ra yielded no significant
      differences in production of the three chemokines at all time points.
      Histological analysis of granulomas did not show any significant differences in
      granuloma numbers, size and M. tuberculosis growth in CCR5-/- compared to wild
      type mice. CONCLUSIONS: The production of the CCR5 ligands, MIP-1alpha, MIP
      1beta, and RANTES, does not clearly correlate with virulence of M. tuberculosis.
      These ligands and their receptors may not be indispensable to the development of
      granulomas in murine tuberculosis.

PMID- 15850758
TI  - Identification of the sequences involved in the glucose-repressed transcription
      of the Streptomyces halstedii JM8 xysA promoter.
AB  - The expression of xysA, a gene encoding for an endoxylanase from Streptomyces
      halstedii JM8, is repressed by glucose. In order to define the regions involved
      in its regulation, several deletions were made in the 475 bp xysA promoter and
      were studied using the melC operon from S. glaucescens as a reporter. Four of the
      deleted versions obtained were seen to be derepressed when driving melC or its
      own xysA gene expression in Streptomyces lividans. Quantitative assays revealed
      that the activity of xylanase produced under the control of these four deleted
      promoters was higher than the original one in the presence of glucose. Three
      regions - RI, R16 and R21 - involved in glucose repression were defined in this
      analysis: RI is a palindromic sequence that is highly conserved among xylanase
      gene promoters from Actinomycetes (-213 GAAAxxTTTCxGAAA -197) and, R16 and R21
      define two new seven-pair conserved motifs, respectively (-113 5'-CCTTCCC-3' -106
      in R16 and -76 5'-CGAACGG-3' -69 in R21) located in the untranslated mRNA. Gel
      shift assays demonstrated the existence of proteins that bind specifically to
      these regions.

PMID- 15850759
TI  - Epilepsy and variation in the frontal lobe artery.
AB  - A patient with a rare variation of fronto-orbital artery (FOA) that developed
      generalized tonic and clonic seizures is reported. The epilepsy focus was in her
      left frontal region, where blood was supplied by the contralateral fronto-orbital
      artery. The region was vulnerable to ischemic changes due to a decrease in blood
      CO2 gas caused by an increase in endogenous progesterone in the luteal period.
      The anomaly illustrates an important mechanism of ischemia in epilepsy.

PMID- 15850762
TI  - Chronotherapeutics: a surge of ideas.
AB  - Chronotherapeutics is advancing hypertension treatments beyond once-daily dosing
      by synchronizing the maximum levels of medication during times when
      cardiovascular risk is highest. It has long been established that patients are at
      higher risk for cardiovascular events-including myocardial infarction, stroke,
      and sudden death-in the early morning hours. Using novel oral delivery methods,
      chronotherapeutic medication synchronizes the delivery of blood pressure drug
      within the period of rates risk, significantly reducing both absolute blood
      pressure numbers and, especially important, the rate of blood pressure increase.
      These therapies have also shown the ability to maintain adequate blood pressure
      levels during the trough period. Several blood pressure medications now have
      chronotherapeutic formulations including the calcium channel blockers verapamil
      and diltiazem and the beta-blocker propranolol.

PMID- 15850760
TI  - Actinobacillus actinomycetemcomitans-induced periodontal disease in mice:
      patterns of cytokine, chemokine, and chemokine receptor expression and leukocyte
      migration.
AB  - Although the pathogenesis of periodontal disease (PD) is not well known,
      cytokines, chemotactic factors and inflammatory cells are certainly involved in
      the disease outcome. Here, we characterized the evolution of the PD induced by
      Actinobacillus actinomycetemcomitans in mice, showing that oral inoculation of
      these bacteria leads to the migration of leukocytes to periodontal tissues and
      marked alveolar bone resorption. We found the expression of pro-inflammatory and
      Th1-type cytokines including TNF-alpha, IFN-gamma and IL-12 in periodontal
      tissues after infection with A. actinomycetemcomitans, from the early stages
      after infection and throughout the course of the disease. Similar kinetics of
      expression were found for the chemokines CCL5, CCL4, CCL3 and CXCL10 and for the
      receptors CCR5 and CXCR3, all of them linked to the Th1-type pattern. The
      expression of the Th2-type mediators IL-10, CCL1 and their receptors CCR4 and
      CCR8 was detected only after 30 days of infection, determining a time-dependent
      mixed pattern of polarized immune response. The chemokine expression was
      correlated with the presence of polymorphonuclear leukocytes, macrophages, CD4
      and CD8 lymphocytes, and B cells in the inflammatory infiltrate. Interestingly,
      during the predominance of the Th1-type response, a sharp increase in the number
      of inflammatory cells and intense bone loss was seen. By contrast, after the
      increased expression of Th2-type mediators, the number of inflammatory cells
      remained constant. Our data demonstrate that mice subjected to oral inoculation
      of A. actinomycetemcomitans represent a useful model for the study of PD. In
      addition, our results suggest that expression of cytokines and chemokines can
      drive the selective recruitment of leukocyte subsets to periodontal tissues,
      which could determine the stable or progressive nature of the lesion.

PMID- 15850763
TI  - Calcium antagonists and beta-blockers: impact on cardiovascular and
      cerebrovascular events.
AB  - It is well established that elevated blood pressure is a major risk factor for
      cardiovascular and cerebrovascular events, and that controlling hypertension
      reduces these risks. Although most classes of antihypertensive agents play a role
      in risk reduction, none offers blanket reductions for all adverse events. The
      beta-blockers, while the agents of choice for those with ischemic heart disease
      and for disease states requiring reducing heart rate, are inappropriate first
      line therapies in patients whose primary concern is stroke risk reduction. In
      patients who require heart rate-lowering therapy but who cannot tolerate beta
      blockers, long-acting nondihydropyridine calcium antagonists offer the benefits
      of heart rate reduction, as well as the vasodilation that is characteristic of
      the calcium antagonists as a class. This article reviews the data on risk
      reduction involving the beta-blockers and calcium antagonists, as well as other
      antihypertensive classes that have been shown to reduce the risk of
      cerebrovascular and cardiovascular disease.

PMID- 15850764
TI  - Optimizing hypertension and vascular health: focus on ethnicity.
AB  - Black individuals are at significantly higher risk for hypertension and its
      sequelae, including end-stage renal disease and congestive heart failure,
      compared with other ethnic groups. The reason for this increased risk is likely
      multifactorial: although genetic differences may play a partial role in the
      etiology and pathophysiology of hypertension in black patients, factors related
      to lifestyle, most notably high body mass index, appear to have a greater impact.
      The treatment approach to lowering blood pressure in blacks is the same as for
      other ethnic groups. Patients should be aggressively managed, using combination
      therapies in the majority of them to achieve optimal blood pressure control and
      thereby cardiorenal protection. Although blockers of the renin-angiotensin system
      (RAS) appear to be less effective for lowering blood pressure and preventing
      kidney disease in blacks compared with whites, black patients have been
      underrepresented in studies of RAS blockers. Calcium channel blockers are
      distinctive for their potent blood pressure-lowering effects, and novel
      strategies such as chronotherapeutic dosing of these agents has further improved
      upon the flexibility of their use.

PMID- 15850765
TI  - Calcium channel blockers and the kidney.
AB  - Although end-stage renal disease (ESRD) currently affects only a small percentage
      (<0.2%) of the US population, its precursor, the mild and moderate forms of
      chronic kidney disease (CKD), affects 11% of the population, with significant
      growth in both ESRD and CKD anticipated in the rapidly aging US population. The
      primary diagnoses in the majority of ESRD patients are diabetes and hypertension.
      Results of clinical studies demonstrate that the level of proteinuria and
      sympathetic activation contribute to the progression of CKD to ESRD. There are
      sufficient clinical data to demonstrate that the dihydropyridine calcium channel
      blocker (DHP CCB) class of antihypertensives such as amlodipine and nifedipine,
      although effective in reducing systemic hypertension, lack activity in reducing
      proteinuria or attenuating sympathetic activity. Experimental studies and a
      limited number of clinical studies suggest that non-DHP CCBs, including verapamil
      and diltiazem, have a mechanism of action that differs from DHP CCBs. Non-DHP
      CCBs could potentially attenuate sympathetic activity and reduce protein
      excretion in patients with CKD.

PMID- 15850766
TI  - Calcium channel blockers in the treatment of hypertension and prevention of
      cardiovascular disease: results from major clinical trials.
AB  - The ability of antihypertensive agents such as ss-blockers and thiazide and
      thiazide-like diuretics to reduce the risk of cardiovascular disease is well
      documented. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart
      Attack Trial (ALLHAT) was undertaken to determine whether the newer classes of
      antihypertensive drugs-namely, calcium channel blockers (CCBs), alpha-1 blockers,
      and angiotensinconverting enzyme (ACE) inhibitors-were as effective as the older
      agents in preventing cardiovascular events. The results of ALLHAT showed that the
      diuretic chlorthalidone, the CCB amlodipine, and the ACE inhibitor lisinopril
      were equally effective in preventing the primary outcome-fatal coronary heart
      disease or nonfatal myocardial infarction. However, chlorthalidone and lisinopril
      were more effective at preventing heart failure, whereas amlodipine and
      chlorthalidone were more effective than lisinopril at preventing stroke. The
      ALLHAT findings, as well as those of other large, randomized, controlled
      antihypertensive trials, confirm the value of lowering blood pressure as an
      approach to reducing the risk, incidence, and economic burden of cardiovascular
      disease.

PMID- 15850767
TI  - Effect of calcium antagonists on plasma norepinephrine levels, heart rate, and
      blood pressure.

PMID- 15850768
TI  - Blood pressure morning surge and hostility.

PMID- 15850769
TI  - Alzheimer's disease: channeling APP to non-amyloidogenic processing.
AB  - A good number of pharmacologic agents have over the years been touted as
      potentially beneficial in either preventing the onset or delay the progression of
      Alzheimer's disease. These include compounds such as non-steroidal anti
      inflammatory drugs (NSAIDs) (HMG-CoA reductase inhibitors (statins)) and
      flavonoids. The underlying mechanisms for the beneficial effect of these agents
      are by and large attributed to their ability to reduce beta-amyloid (Abeta)
      production and amyloid load in the brain, via inhibition of amyloidogenic gamma
      secretase activity. Recent reports have now provided mechanistic insights as to
      how non-amyloidogenic processing might also be enhanced by these seemingly
      unrelated treatments. Intriguingly, this appears to involve the inhibition of the
      activity of small GTPase Rho and its effector, the Rho-associated kinase, ROCK.
      Dietary caloric restriction (CR) also enhances non-amyloidogenic processing of
      APP, and this may be part of a more general anti-aging effect of CR mediated by
      gene expression changes downstream of the activity of the histone deacetylase
      SIRT1.

PMID- 15850770
TI  - Polyprenyl lipid synthesis in mammalian cells expressing human cis-prenyl
      transferase.
AB  - The level of cis-prenyl transferase activity has been implicated in controlling
      the level of biosynthesis of dolichol and dolichol intermediates. In this study,
      we isolated a cDNA encoding a human CPT (GenBank Accession No. ), which had
      substantial homology to other CPT isolated from human brain, bacteria,
      Arabidopsis, and Saccharomyces cerevisiae. Expression of this cDNA in two
      different insect cell lines confirmed the functionality of the protein in an in
      vitro assay. Western blot analysis revealed an expressed protein of approximately
      38 kDa in HEK293 cells. Overexpression of the protein in HEK293 cells resulted in
      an increase in the level of total prenol in vivo. Furthermore, product
      characterization by thin layer chromatography (TLC) confirmed that the major
      product was a long-chain prenol with a chain length of 95 carbons. These results
      suggest a regulatory relationship between CPT activity and dolichol biosynthesis,
      and may implicate CPT in the levels of dolichol-oligosaccharide intermediate
      biosynthesis.

PMID- 15850771
TI  - TWEAK mediates anti-tumor effect of tumor-infiltrating macrophage.
AB  - TWEAK induces diverse cellular responses, including pro-inflammatory chemokine
      production, migration, proliferation, and cell death through the TWEAK receptor,
      Fn14. In the present study, we examined the effect of TWEAK or Fn14 expression in
      tumor cells on tumor outgrowth in vivo. Administration of neutralizing anti-TWEAK
      mAb significantly reduced the frequency of tumor rejection and shortened the
      survival of mice intraperitoneally inoculated with TWEAK-sensitive Fn14
      expressing tumor cells. Moreover, anti-TWEAK mAb treatment promoted the
      subcutaneous growth of TWEAK-sensitive Fn14-expressing tumor cells, and this
      promotion was abolished by the inhibition of macrophage infiltration but not NK
      cell depletion. In contrast, administration of anti-TWEAK mAb had no apparent
      effect on the growth of TWEAK-resistant tumor cells, even if tumor cells
      expressed Fn14. On the other hand, TWEAK expression in tumor cells had no
      significant effect on subcutaneous tumor growth. These results indicate that
      TWEAK mediates anti-tumor effect of macrophages in vivo.

PMID- 15850772
TI  - Inhibition of the PI3K pathway sensitizes fludarabine-induced apoptosis in human
      leukemic cells through an inactivation of MAPK-dependent pathway.
AB  - In the present study, we have investigated the effects of PI3K/Akt pathway on the
      response of human leukemia cells to fludarabine. Inhibition of PI3K/Akt pathway
      with a selective inhibitor (e.g., LY294002, or wortmannin) in leukemic cells
      markedly potentiated fludarabine-induced apoptosis. Inhibition of the PI3K/Akt
      downstream target mTOR by rapamycin also significantly enhanced fludarabine
      induced apoptosis. The co-treatment of fludarabine/LY294002 resulted in
      significant attenuation in the levels of both phospho-Erk1/2 and phospho-Akt, as
      well as a marked increase in the level of phospho-JNK. The broad spectrum caspase
      inhibitor BOC-D-fmk markedly blocked fludarabine/LY-induced apoptosis, had no
      effect on cytochrome c release to the cytosol, and did abrogate caspase and PARP
      cleavage. This indicates that mitochondrial dysfunction is upstream of the
      caspase cascade. Moreover, constitutive activation of the MEK/Erk pathway
      completely blocked apoptosis induced by the combination of fludarabine/LY294002.
      Additionally, either constitutive activation of Akt or blockage of the JNK
      pathway significantly diminished apoptosis induced by the combination.
      Collectively, these findings demonstrate that inactivation of MAPK, Akt, and
      activation of the JNK pathway contributes to the induction of apoptosis induced
      by fludarabine/LY. Comparatively, MAPK inactivation plays a crucial role in
      fludarabine/LY-induced apoptosis. These results also strongly suggest that
      combining fludarabine with an inhibitor of the PI3K/Akt/mTOR pathway may
      represent a novel therapeutic strategy for hematological malignancies.

PMID- 15850773
TI  - SF2/ASF protein binds to the cap region of human topoisomerase I through two RRM
      domains.
AB  - DNA relaxation catalysed by topoisomerase I is based on the reversible DNA
      cleavage. The reaction is inhibited by binding of splicing protein SF2/ASF, a
      substrate for the kinase activity of topoisomerase I. In this paper, we show a
      novel binding site for SF2/ASF in the cap region of topoisomerase I (amino acids
      215-433) which interacts with the region containing two closely spaced RRM
      domains of SF2/ASF (amino acids 1-194). The sites were defined by a set of pull
      down experiments with isolated recombinant polypeptides. We also indicate that
      the novel site is responsible for the inhibition of DNA cleavage. The polypeptide
      containing tandem RRM domains inhibited DNA cleavage by topoisomerase I similarly
      as the complete SF2/ASF. Moreover, interaction between the tandem RRM domains and
      the cap region was not possible in the presence of DNA.

PMID- 15850774
TI  - Targeting of alpha(v) integrins interferes with FAK activation and smooth muscle
      cell migration and invasion.
AB  - Aberrant migration of smooth muscle cells (SMCs) is a key feature of restenosis.
      Since extracellular matrix proteins and their receptors of the integrin family
      play a critical role in this process, it is instrumental to understand their
      contribution to cell migration and invasive motility of SMC on the molecular
      level. Therefore, we investigated the role of alpha(v)-containing integrins
      expressed by primary human coronary artery smooth muscle cells (hCASMCs) in
      vitronectin (VN)-initiated signaling events and cell migration. In hCASMC plated
      on VN, alpha(v)-containing integrins were localized at focal adhesion sites.
      Haptotactic stimulation through VN led to a dose-dependent increase in cell
      migration and concomitantly to enhanced tyrosine phosphorylation of focal
      adhesion kinase. Both events were completely blocked by a specific inhibitor of
      integrin alpha(v). Additionally, the integrin alpha(v) inhibitor abolished PDGF
      BB-stimulated chemotactic migration. Confocal microscopy confirmed the increased
      tyrosine phosphorylation at VN-initiated focal contact sites in hCASMC, that was
      abolished upon alpha(v) inhibition. In vitro invasion of hCASMC was severely
      compromised in the presence of the integrin alpha(v) inhibitor paralleled by
      decreased levels of secreted matrix metalloprotease 2 (MMP-2). Together, integrin
      alpha(v) inhibition abrogates tyrosine phosphorylation at focal adhesion sites
      and diminishes MMP-2 secretion leading to reduced migration and invasion of
      hCASMCs.

PMID- 15850775
TI  - Novel intermediate of Rac GTPase activation by guanine nucleotide exchange
      factor.
AB  - The biochemical role of guanine nucleotide exchange factors (GEFs) in catalyzing
      small GTPase GDP-GTP exchange is thought to be twofold: stimulation of GDP
      dissociation and stabilization of a nucleotide-free GTPase intermediate. Here we
      report that TrioN, a Dbl family GEF, activates Rac1 by facilitating GTP binding
      to, as well as stimulating GDP dissociation from, Rac1. The TrioN-catalyzed GDP
      dissociation is dependent upon the structural nature and the concentration of
      free nucleotide, and nucleotide binding serves as the rate-limiting step of the
      GEF reaction. The TrioN-stimulated nucleotide exchange may undergo a novel two
      nucleotide-one G-protein intermediate involving two cryptic subsites on Rac1
      induced by the GEF, with one subsite contributing to the recognition of the
      beta/gamma phosphates of the incoming GTP and another to the binding of the
      guanine base of the leaving GDP. We propose that the Rac GEF reaction may proceed
      by competitive displacement of bound GDP by GTP through a transient intermediate
      of GEF-[GTP-Rac-GDP].

PMID- 15850776
TI  - Membrane cholesterol oxidation inhibits ligand binding function of hippocampal
      serotonin(1A) receptors.
AB  - We have monitored the ligand binding function of the bovine hippocampal 5-HT(1A)
      receptor following treatment of native membranes with cholesterol oxidase.
      Cholesterol oxidase is a water soluble enzyme that acts on the membrane interface
      to catalyze the conversion of cholesterol to cholestenone. Oxidation of membrane
      cholesterol significantly inhibits the specific binding of the agonist and
      antagonist to 5-HT(1A) receptors. Fluorescence polarization measurements of
      membrane probes incorporated at different locations in the membrane revealed no
      appreciable effect on membrane order due to the oxidation of cholesterol to
      cholestenone. These results therefore suggest that the ligand binding function of
      the 5-HT(1A) receptor is a cholesterol-dependent phenomenon that is not related
      to the ability of cholesterol to modulate membrane order. Importantly, these
      results represent the first report on the effect of a cholesterol-modifying agent
      on the ligand binding function of this important neurotransmitter receptor.

PMID- 15850777
TI  - Three dimensional nanofibrillar surfaces induce activation of Rac.
AB  - Studies to define the mechanisms by which the extracellular matrix (ECM)
      activates Rho GTPases within the cell have generally focused on the chemistry of
      the macromolecules comprising the ECM. Considerably less information is available
      to assess the role of the physical structure of the ECM, particularly its three
      dimensional (3D) geometry. In this report, we examined the effect of 3D surfaces
      on the activation states of Rho GTPases within NIH 3T3 fibroblasts and normal rat
      kidney cells. Cells were cultured on synthetic 3D surfaces comprised of polyamide
      nanofibers. In contrast to results using two dimensional tissue culture surfaces,
      growth of both cell types on 3D nanofibrillar surfaces resulted in a preferential
      and sustained activation of the small GTPase Rac. These results support the
      growing view that in addition to chemical composition, the three dimensionality
      and nanofibrillar architecture of ECM may represent another essential element in
      signal transduction pathways and cellular physiology.

PMID- 15850778
TI  - No evidence for association of the TATA-box binding protein glutamine repeat
      sequence or the flanking chromosome 6q27 region with type 1 diabetes.
AB  - Susceptibility to the autoimmune disease type 1 diabetes has been linked to human
      chromosome 6q27 and, moreover, recently associated with one of the genes in the
      region, TATA box-binding protein (TBP). Using a much larger sample of T1D
      families than those studied by others, and by extensive re-sequencing of nine
      other genes in the proximity, in which we identified 279 polymorphisms, 83 of
      which were genotyped in up to 725 T1D multiplex and simplex families, we obtained
      no evidence for association of the TBP CAG/CAA (glutamine) microsatellite repeat
      sequence with disease, or for nine other genes, PDCD2, PSMB1, KIAA1838, DLL1,
      dJ894D12.4, FLJ25454, FLJ13162, FLJ11152, PHF10 and CCR6. This study also
      provides an exon-based tag single nucleotide polymorphism map for these 10 genes
      that can be used for analysis of other diseases.

PMID- 15850779
TI  - Statins downregulate myeloperoxidase gene expression in macrophages.
AB  - Statins, inhibitors of HMG-CoA reductase, have pleiotropic benefits independent
      of cholesterol levels, including anti-oxidant and anti-inflammatory effects.
      Here, we investigate the effect of statins on myeloperoxidase (MPO) expression.
      MPO, expressed in foam cell macrophages, was recently shown to oxidize the ApoA-1
      component of HDL, impairing ABCA-1 mediated cholesterol efflux. High levels of
      serum MPO correlate with increased risk of CAD events. Findings here show that
      statins strongly inhibit MPO mRNA expression in human and murine monocyte
      macrophages. Suppression was reversed by downstream intermediates of HMG-CoA
      reductase, mevalonate, and geranylgeranylpyrophosphate, but not
      farnesylpyrophosphate. An inhibitor of geranylgeranyltransferase, GGTI-286,
      mimics the effects of statins, indicating geranylgeranylation is key to MPO
      expression. Reduction of MPO mRNA levels was observed in vivo in leukocytes from
      statin-fed mice, correlating with reductions in MPO protein and enzyme activity.
      These findings suggest that the pleiotropic protections afforded by statins may
      be due in part to suppression of MPO expression.

PMID- 15850780
TI  - Monitoring of the ethionamide pro-drug activation in mycobacteria by (1)H high
      resolution magic angle spinning NMR.
AB  - In this study, we use HRMAS NMR as a non-invasive technique to monitor the in
      vivo metabolism of a xenobiotic. The antituberculosis Ethionamide is a pro-drug
      that has to be activated in mycobacteria before inhibiting its cellular target.
      The use of (1)H HRMAS NMR has allowed to detect a metabolite (ETH*) of the drug
      directly in living bacteria, even with a spectrometer operating at the relatively
      low magnetic field of 300MHz. We show that metabolism monitoring of an unlabelled
      drug at a therapeutically relevant concentration as low as 5mug/ml is within
      reach of the technique. (1)H HRMAS NMR in combination with diffusion filtering
      leads to the conclusion that the metabolite is located inside the intact cells.
      The comparison of the metabolite NMR signature with that of synthetic molecules
      proves the non-identity of ETH* with the ETH derivatives described previously in
      the literature.

PMID- 15850781
TI  - RNA interference: a mammalian SID-1 homologue enhances siRNA uptake and gene
      silencing efficacy in human cells.
AB  - SID-1 is a transmembrane protein that mediates systemic RNA interference in
      Caenorhabditis elegans. Here we show that the mammalian SID-1 homologue FLJ20174
      localizes to the cell membrane of human cells and enhances their uptake of small
      interfering RNA (siRNA), resulting in increased siRNA-mediated gene silencing
      efficacy. This is the first demonstration to show that overexpression of a
      membrane protein enhances siRNA internalization in mammalian cells. This
      observation raises the possibility of enhancing the efficacy of RNA interference.

PMID- 15850782
TI  - Bacterially produced human HIF-1alpha is competent for heterodimerization and
      specific DNA-binding.
AB  - Hypoxia-inducible factor 1alpha (HIF-1alpha) is the regulatory subunit of HIF-1,
      the transcriptional activator and key mediator of the cellular response to
      hypoxia. Regulation of HIF-1alpha occurs at multiple levels and involves several
      different post-translational modifications. In order to examine the importance of
      these modifications for the basic function of HIF-1alpha, we have produced in
      bacteria recombinant full-length human HIF-1alpha using different expression
      systems. We show that this unmodified form of HIF-1alpha is able to form a stable
      heterodimer with the second subunit of HIF-1 (HIF-1beta or ARNT) when both
      proteins are co-expressed in Escherichia coli. Furthermore, this bacterially
      reconstituted heterodimer exhibits specific DNA-binding activity. These data
      indicate that post-translational modification of HIF-1alpha is not essential for
      its interaction with ARNT and DNA, and provide an in vitro system for the
      characterization of the molecular properties of HIF-1alpha.

PMID- 15850783
TI  - Firefly luciferase exhibits bimodal action depending on the luciferin chirality.
AB  - Firefly luciferase is able to convert L-luciferin into luciferyl-CoA even under
      ordinary aerobic luciferin-luciferase reaction conditions. The luciferase is able
      to recognize strictly the chirality of the luciferin structure, serving as the
      acyl-CoA synthetase for L-luciferin, whereas d-luciferin is used for the
      bioluminescence reaction. D-Luciferin inhibits the luciferyl-CoA synthetase
      activity of L-luciferin, whereas L-luciferin retards the bioluminescence reaction
      of D-luciferin, meaning that both enzyme activities are prevented by the
      enantiomer of its own substrate.

PMID- 15850784
TI  - Identification of non-mitochondrial NADPH oxidase and the spatio-temporal
      organization of its components in mouse spermatozoa.
AB  - Though the spermatozoa are known to produce superoxide anion radicals, the enzyme
      system(s) that produce superoxide in these cells are not yet identified. Using
      Western blot assays and confocal laser scan microscopy, we detected gp91(phox)
      and p67(phox) associated with spermatozoa from testis and epididymis. We could
      not detect p22(phox) in any of the sperm samples analyzed. While the expression
      of gp91(phox) p67(phox) appeared to be constitutive, p47(phox) was detectable
      only in spermatozoa from testis and vas deferens. Importantly, p40(phox) could be
      seen in very high quantities in testicular spermatozoa, which also showed the
      highest levels of NADPH-oxidase activity. Spermatozoa from cauda epididymidis and
      vas deferens also showed the presence of p40(phox), though the amount was low
      when compared with that of testicular spermatozoa. The absence of p22(phox) and
      the striking correlation between the presence of p40(phox) and the NADPH-oxidase
      activity suggest that the NADPH oxidase associated with spermatozoa is p22(phox)
      independent and that its activity is positively modulated by p40(phox). Further,
      since the confocal imaging detected that the subunits of the NADPH oxidase are
      located significantly on the head domains, the spermatozoa appear to present a
      case with dominant non-mitochondrial superoxide anion producing capabilities.

PMID- 15850785
TI  - Identification of the promoter region required for human adiponectin gene
      transcription: Association with CCAAT/enhancer binding protein-beta and tumor
      necrosis factor-alpha.
AB  - Adiponectin, an adipose tissue-specific plasma protein, is involved in insulin
      sensitizing and has anti-atherosclerotic properties. Plasma levels of adiponectin
      are decreased in obese individuals and patients with type 2 diabetes with insulin
      resistance. Tumor necrosis factor-alpha (TNF-alpha) decreases the expression of
      adiponectin in adipocytes. The aims of the present study were: (1) to identify
      the promoter region responsible for basal transcription of the human adiponectin
      gene, and (2) to investigate the mechanism by which adiponectin was regulated by
      TNF-alpha. The human adiponectin promoter (2.1kb) was isolated and used for
      luciferase reporter analysis by transient transfection into 3T3-L1 adipocytes.
      Deletion analysis demonstrated that the promoter region from -676 to +41 was
      sufficient for basal transcriptional activity. Mutation analysis of putative
      response elements for sterol regulatory element binding protein (SREBP) (-431 to 
      423) and CCAAT/enhancer binding protein (C/EBP) (-230 to -224) showed that both
      elements were required for basal promoter activity. Adiponectin transcription was
      increased 3-fold in cells that over-expressed constitutively active C/EBP-beta.
      Electrophoretic mobility shift assay, using nuclear extract from 3T3-L1 cells and
      the -258 to -199 region as a probe, demonstrated specific DNA-protein binding,
      which was abolished by TNF-alpha treatment. The present data indicate that the
      putative response elements for SREBP and C/EBP are required for human adiponectin
      promoter activity, and that suppression by TNF-alpha may, at least in part, be
      associated with inactivation of C/EBP-beta.

PMID- 15850786
TI  - Mice with elevated muscle glycogen stores do not have improved exercise
      performance.
AB  - Skeletal muscle glycogen is considered to be an important source of energy for
      contraction and increasing the level of the glucose polymer is generally thought
      to improve exercise performance in humans. A genetically modified mouse model
      (GSL30), which overaccumulates glycogen due to overexpression of a hyperactive
      form of glycogen synthase, was used to examine whether increasing the level of
      the polysaccharide enhances the ability of mice to run on a treadmill. The
      skeletal muscle of the GSL30 mice had large deposits of glycogen. There were no
      significant increases in the work performed by GSL30 mice as compared to their
      respective wild type littermates when exercised to exhaustion. The amount of
      muscle glycogen utilized by GSL30 mice, however, was greater, while the amount of
      liver glycogen consumed during exhaustive exercise was less than wild type
      animals. This result suggests that increased muscle glycogen stores do not
      necessarily improve exercise performance in mice.

PMID- 15850787
TI  - Sap-1/PTPRH activity is regulated by reversible dimerization.
AB  - Sap-1/PTPRH, a receptor protein tyrosine phosphatase (RPTP), is a ubiquitously
      expressed enzyme that is upregulated in human gastrointestinal cancers. Using
      both chemical cross-linkers and co-immunoprecipitation we show that overexpressed
      full-length Sap-1 is present as a stable homodimer. Unlike a number of adhesion
      RPTPs which have tandem catalytic domains that are involved in dimerization, Sap
      1 has a single catalytic domain, and we show that this domain is not required for
      Sap-1 dimerization, which is mediated instead by the large extracellular and
      transmembrane domains. Exposing cells that express the receptor to a reducing
      environment reversibly disrupts the Sap-1 dimer, suggesting that cysteine bonds
      play a role in dimer formation/stabilization. The switch between Sap-1 dimers and
      monomers is accompanied by an increase in catalytic activity as judged by its
      capacity to dephosphorylate and activate c-src, which we identify as a novel
      substrate for this phosphatase.

PMID- 15850788
TI  - Chronic exposure to EGF affects trafficking and function of ENaC channel in
      cystic fibrosis cells.
AB  - Using the whole-cell patch-clamp technique, we identified an amiloride (AMI)
      sensitive Na(+) current in cystic fibrosis cells, JME/CF15, growing in standard
      medium. The reversal potential of this current depended on Na(+) concentrations
      and the cation selectivity was much higher for Na(+) than for K(+), indicating
      that the current is through ENaC channels. In contrast, cells from EGF-containing
      medium lacked AMI-sensitive Na(+) currents. In permeabilized cells growing in EGF
      containing medium, alphaENaC was mainly detected in a perinuclear region, while
      in cells from standard medium it was distributed over the cell body. Western-blot
      analysis showed that in standard medium cells expressed fast-migrating EndoH
      insensitive and slow-migrating EndoH-sensitive alphaENaC fractions, while in
      cells growing in the presence of EGF, alphaENaC was only detected as the fast
      migrating EndoH-insensitive fraction. Long-term incubation of cells with EGF
      resulted in an increased basal Ca(2+) level, [Ca(2+)](i). A similar increase of
      [Ca(2+)](i) was also observed in the presence of 2muM thapsigargin, resulting in
      inhibition of ENaC function. Thus, in JME/CF15 cells inhibition of the ENaC
      function by chronic incubation with EGF is a Ca(2+)-mediated process that affects
      trafficking and surface expression of ENaC channels.

PMID- 15850789
TI  - Comparative analysis of human intronless proteins.
AB  - The availability of the complete genome sequences of Homo sapiens together with
      those of taxonomically diverse organisms provides an opportunity to carry out
      cross-species comparison. Comparisons of protein sequences from different
      organisms are significant source of information as these could help in answering
      questions regarding the fraction of proteins that are shared by humans and
      organisms representing the three domains of life, viz., archaea, bacteria, and
      eukaryota. In the present study, a comparative analysis of the proteins encoded
      by intronless genes in humans was undertaken. We identified 1125 human intronless
      proteins that are solely present in eukaryotic lineage. More than two-thirds of
      these eukaryotic specific proteins appear to be mammalia specific while a small
      fraction of proteins are conserved in bilateria and coelomata, indicating that
      diversification of these proteins occurred after the divergence of the major
      lineages of the eukaryotic crown group. A large fraction of mammalia specific
      proteins are enriched in proteins responsible for transport and binding, cell
      envelope, and housekeeping function particularly translation. Another 228
      intronless proteins are observed that do not exhibit homology to any of the
      proteins in the database. The distribution of human intronless proteins suggests
      that lineage specific expansion is one of the most important sources of
      organizational diversity in crown-group eukaryotes. The presence of these
      eukaryotic as well as human specific intronless proteins provides the foundation
      for rapid analysis of some of the basic processes involved in human genome.

PMID- 15850790
TI  - Adiponectin increases bone mass by suppressing osteoclast and activating
      osteoblast.
AB  - Adiponectin, an adipose-derived hormone, exhibits various biological functions,
      such as increasing insulin sensitivity, protecting hypertension, and suppression
      of atherosclerosis, liver fibrosis, and tumor growth. Here, we report the role of
      adiponectin on bone metabolism. C57BL/6J mice were treated with adenovirus
      expressing lacZ or adiponectin, and their bones were analyzed by three
      dimensional microcomputed tomography. Adiponectin-adenovirus treatment increased
      trabecular bone mass, accompanied by decreased number of osteoclasts and levels
      of plasma NTx, a bone-resorption marker. In vitro studies showed that adiponectin
      inhibited M-CSF- and RANKL-induced differentiation of mouse bone marrow
      macrophages and human CD14-positive mononuclear cells into osteoclasts and also
      suppressed the bone-resorption activity of osteoclasts. Furthermore, adiponectin
      enhanced mRNA expression of alkaline phosphatase and mineralization activity of
      MC3T3-E1 osteoblasts. Our results indicate that adiponectin exerts an activity to
      increase bone mass by suppressing osteoclastogenesis and by activating
      osteoblastogenesis, suggesting that adiponectin manipulation could be
      therapeutically beneficial for patients with osteopenia.

PMID- 15850791
TI  - Molecular and structural characterization of fluorescent human parvovirus B19
      virus-like particles.
AB  - Although sharing a T=1 icosahedral symmetry with other members of the
      Parvoviridae family, it has been suggested that the fivefold channel of the human
      parvovirus B19 VP2 capsids is closed at its outside end. To investigate the
      possibility of placing a relatively large protein moiety at this site of B19,
      fluorescent virus-like particles (fVLPs) of B19 were developed. The enhanced
      green fluorescent protein (EGFP) was inserted at the N-terminus of the structural
      protein VP2 and assembly of fVLPs from this fusion protein was obtained. Electron
      microscopy revealed that these fluorescent protein complexes were very similar in
      size when compared to wild-type B19 virus. Further, fluorescence correlation
      spectroscopy showed that an average of nine EGFP domains were associated with
      these virus-like structures. Atomic force microscopy and immunoprecipitation
      studies showed that EGFP was displayed on the surface of these fVLPs. Confocal
      imaging indicated that these chimeric complexes were targeted to late endosomes
      when expressed in insect cells. The fVLPs were able to efficiently enter cancer
      cells and traffic to the nucleus via the microtubulus network. Finally,
      immunoglobulins present in human parvovirus B19 acute and past-immunity serum
      samples were able to detect antigenic epitopes present in these fVLPs. In
      summary, we have developed fluorescent virus-like nanoparticles displaying a
      large heterologous entity that should be of help to elucidate the mechanisms of
      infection and pathogenesis of human parvovirus B19. In addition, these B19
      nanoparticles serve as a model in the development of targetable vehicles designed
      for delivery of biomolecules.

PMID- 15850792
TI  - Evidence for Cd101 but not Fcgr1 as candidate for type 1 diabetes locus, Idd10.
AB  - Among polygenes conferring susceptibility to type 1 diabetes in the NOD mouse,
      Idd10 on distal chromosome 3 has been shown to be important for disease
      susceptibility. In this study, we investigated the candidacy of Fcgr1 and Cd101
      for Idd10, by congenic mapping and candidate gene sequencing. Among seven NOD
      related strains studied, the IIS mouse was found to possess a recombinant Idd10
      interval with the same sequence at Fcgr1 as the NOD mouse, but a different
      sequence at Cd101 from that in the NOD mouse with 10 amino acid substitutions.
      The frequency of type 1 diabetes in NOD mice congenic for IIS Idd10
      (NOD.IISIdd10) was significantly reduced as compared to that in the NOD mouse,
      despite the presence of the identical Fcgr1 sequence. These data indicate that
      IIS mice possess a resistant allele at Idd10, and suggest that Cd101, but not
      Fcgr1, is responsible for the Idd10 effect.

PMID- 15850793
TI  - SOCS-1 inhibits expression of the antiviral proteins 2',5'-OAS and MxA induced by
      the novel interferon-lambdas IL-28A and IL-29.
AB  - Recently, we have shown that SOCS-1/3 overexpression in hepatic cells abrogates
      signaling of type I interferons (IFN) which may contribute to the frequently
      observed IFN resistance of hepatitis C virus (HCV). IFN-lambdas (IL-28A/B and IL
      29), a novel group of IFNs, also efficiently inhibit HCV replication in vitro
      with potentially less hematopoietic side effects than IFN-alpha because of
      limited receptor expression in hematopoietic cells. To further evaluate the
      potential of IFN-lambdas in chronic viral hepatitis, we examined the influence of
      SOCS protein expression on IFN-lambda signaling. First, we show that hepatic cell
      lines express the IFN-lambda receptor complex consisting of IFN-lambdaR1 (IL
      28R1) and IL-10R2. Whereas in mock-transfected HepG2 cells, IL-28A and IL-29
      induced STAT1 and STAT3 phosphorylation, overexpression of SOCS-1 completely
      abrogated IL-28A and IL-29-induced STAT1/3 phosphorylation. Similarly, IL-28A and
      IL-29 induced mRNA expression of the antiviral proteins 2',5'-OAS and MxA was
      abolished by overexpression of SOCS-1. In conclusion, we assume that despite
      antiviral properties of IFN-lambdas, their efficacy as antiviral agents may have
      similar limitations as IFN-alpha due to inhibition by SOCS proteins.

PMID- 15850794
TI  - MccJ25 C-terminal is involved in RNA-polymerase inhibition but not in respiration
      inhibition.
AB  - Microcin J25 appears to have two intracellular targets: (1) RNA polymerase, which
      was described in Escherichia coli and Salmonella enterica serovars, and (2) cell
      respiration in Salmonella enterica serovars. C-terminal glycine amidation of the
      threaded segment localized in the MccJ25 lariat ring region specifically blocked
      the RNA-polymerase inhibition, but not the cell respiration inhibition and
      peptide uptake. These results suggest that different regions of the molecule are
      responsible for each cellular effect, they are localized far away from the beta
      hairpin region and the C-terminal region is an important determinant for RNAP
      inhibition.

PMID- 15850795
TI  - Mouse myodulin, a new potential angiogenic factor, functionally expressed in
      yeast.
AB  - Myodulin is a new integral membrane protein down-regulated in skeletal muscle
      atrophy. A first characterization suggested that myodulin could be a skeletal
      muscle angiogenic factor operating through direct cell-to-cell interactions.
      Here, we show that mouse myodulin can be expressed at the plasma membrane of
      Saccharomyces cerevisiae and purified. Co-culture experiments of myoblasts and
      cardiac vascular endothelial cells reveal that myodulin, either presented in
      yeast membranes or in liposomes after purification, increases the invasive
      potential of endothelial cells with a similar efficiency as when over-expressed
      in skeletal muscle cells. Functional essays using myodulin expressed in yeast
      bring new information about the myodulin functional mechanism, suggesting that
      one or several muscle cell components could be necessary for myodulin to increase
      the invasive potential of endothelial cells. The yield of purified myodulin
      should allow structure-function relationships studies for a better understanding
      of myodulin functional mechanisms.

PMID- 15850796
TI  - Characterization of alphaX I-domain binding to Thy-1.
AB  - The beta2 integrins are found exclusively in leukocytes and they are composed of
      a common beta chain, CD18, and one of four unique alpha chains, CD11a (alphaL
      subunit), CD11b (alphaM subunit), CD11c (alphaX subunit), or CD11d (alphaD
      subunit). alphaX-beta2 which binds several ligands including fibrinogen and iC3b
      is expressed in monocytes/macrophages and dendritic cells playing an important
      role in the host defense. Despite the unique characteristics on expression and
      regulation, alphaX-beta2 is less functionally characterized than other beta2
      integrins. To understand the biological function of alphaX-beta2 more, we tested
      the possibility that alphaX-beta2 binds Thy-1, a membrane protein involved in
      cell adhesion and signaling regulation in neurons and T cells. Here we report
      that a ligand binding moiety of alphaX-beta2, the I-domain, bound Thy-1 in a
      specific and divalent cation-dependent manner. The dissociation constant (K(D))
      of alphaX I-domain binding to Thy-1 was 1.16muM and the affinity of the binding
      was roughly 2-fold higher than that of alphaM I-domain. Amino acid substitutions
      on the betaD-alpha5 of alphaX I-domain (D249, KE243/244) showed low affinities
      for Thy-1 while other point mutations on alpha3-alpha4 and betaE-alpha6 loops of
      I-domain did not, suggesting that Thy-1 recognizes the portion of a betaD-alpha5
      loop, possibly alpha5 helix. Taken together, these results indicate that alphaX
      beta2 specifically interacts with Thy-1. Additionally, kinetic analysis reveals a
      moderate affinity interaction in the presence of divalent cations. Given the
      reported role of Thy-1 in the regulation of T cell homeostasis and proliferation,
      it is tempting to speculate that alphaX-beta2 may be involved in Thy-1 function.

PMID- 15850797
TI  - Mass spectral evidence for N-glycans with branching on fucose in a molluscan
      hemocyanin.
AB  - Glycopeptides, isolated from a trypsinolysate of functional unit (FU) RtH2-e of
      Rapana thomasiana hemocyanin subunit 2, were analysed by electrospray ionization
      mass spectrometry and MS/MS. From the molecular mass observed after
      deglycosylation, it was inferred that all glycopeptides shared the same peptide
      stretch 92-143 of FU RtH2-e with a glycosylation site at Asn-127. Besides the
      core structure Man(3)GlcNAc(2) for N-glycosylation, structures with a
      supplementary GlcNAc linked to either the Man(alpha1-3) or the Man(alpha1-6) arm
      and/or an additional tetrasaccharide unit connected to the other Man arm were
      observed, indicating the existence of microheterogeneity at the glycan level. The
      tetrasaccharide unit contains a central fucose moiety substituted with 3-O
      methylgalactose and N-acetylgalactosamine, and linked to GlcNAc at the reducing
      end. This structure represents a novel N-glycan motif and is likely to be
      immunogenic. A second potential site for N-glycosylation in FU RtH2-e at Asn-17
      was shown to be not glycosylated.

PMID- 15850798
TI  - Clostridium botulinum type A progenitor toxin binds to Intestine-407 cells via N
      acetyllactosamine moiety.
AB  - Botulism is a highly fatal disease caused by the botulinum progenitor toxin. In
      this study, the role of oligosaccharides for the binding of botulinum type A
      progenitor toxin (type A PTX) to human intestinal cells was investigated. The
      binding of type A PTX to Intestine-407 cells was inhibited by the addition of N
      acetyllactosamine, lactose, and galactose. Treatment of Intestine-407 cells with
      neuraminidase led to a significant increase in the binding of type A PTX, while
      further digestion of cell surface oligosaccharides by beta-galactosidase and beta
      N-acetylhexosaminidase decreased the binding. These results indicate that the N
      acetyllactosamine moiety is responsible for the binding of type A PTX. These
      findings were further confirmed by a binding assay using synthesized
      oligosaccharides. Interestingly, sialylation or fucosylation of oligosaccharides
      inhibited the binding of type A PTX. These data suggest that the type A PTX binds
      to intestinal cells via cell surface N-acetyllactosamine moiety.

PMID- 15850799
TI  - Stabilization of the fibrous structure of an alpha-helix-forming peptide by
      sequence reversal.
AB  - The alpha3-peptide, which comprises three repeats of the sequence Leu-Glu-Thr-Leu
      Ala-Lys-Ala and forms an amphipathic alpha-helix, is unique among various alpha
      helix-forming peptides in that it assembles into fibrous structures that can be
      observed by transmission electron microscopy. As part of our investigation of the
      structure-stability relationships of the alpha3-peptide, we synthesized the r3
      peptide, whose amino acid sequence is the reverse of that of the alpha3-peptide,
      and we investigated the effects of sequence reversal on alpha-helix stability and
      the formation of fibrous structures. Unexpectedly, the r3-peptide formed a more
      stable alpha-helix and longer fibers than did the alpha3-peptide. The stability
      of the r3-peptide helix decreased when the ionic strength of the buffer was
      increased and when the pH of the buffer was adjusted to 2 or 12. These results
      suggest that the r3-peptide underwent a "magnet-like" oligomerization and that an
      increase in the charge-distribution inequality may be the driving force for the
      formation of fibrous structures.

PMID- 15850800
TI  - Post-transcriptional control of the cyanobacterial hspA heat-shock induction.
AB  - The hspA gene encodes a small heat-shock protein in the thermophilic
      cyanobacterium Synechococcus vulcanus. To gain insight into the post
      transcriptional regulation, hspA was expressed in Escherichia coli. HspA was
      induced upon a temperature upshift from 30 to 42 degrees C, although the hspA
      transcription in E. coli occurred constitutively at both 30 and 42 degrees C.
      Neither replacement of the native hspA promoter with the lacZ promoter nor the
      addition of rifampin abolished the heat induction. Thus, the primary form of
      regulation of the heat induction is at the post-transcriptional level. Analyses
      of expression of a series of the transcriptional and translational hspA-lacZ
      fusions confirmed the constitutive transcription, and demonstrated that the heat
      induction occurred only in the translational fusions. They further indicated the
      presence of regulatory elements involved in the translational regulation. An
      element in the 5'-untranslated region of the hspA mRNA suppressed the
      translation, while that in the hspA coding region was required for the de
      repression of the translation and for thermal regulation.

PMID- 15850801
TI  - T-cell specific enhancement of histone H3 acetylation in 5' flanking region of
      the IL-2 gene.
AB  - The IL-2 gene expression is highly T-cell specific in an activation-dependent
      manner. However, little is known about how T-cell specific expression is
      regulated, although related transcription factors have been identified. To
      address this issue, we examined the chromatin structure change of the IL-2 gene
      by analyzing histone acetylation status in the upstream of IL-2 gene
      transcription initiation site. Interestingly, the histone acetylation level was
      found to be higher in various sites on the widespread upstream region in resting
      T-cells than resting B-cells. After T-cell stimulation with PMA and ionomycin,
      the same regions were further acetylated on histone H3. Particularly, the distal
      enhancer region showed prompt enhancement of histone acetylation, followed by the
      IL-2 mRNA expression. These results suggest that the 5' flanking region including
      the distal enhancer region of the IL-2 gene is already accessible in T cells with
      constitutive acetylation of histone H3,which may serve for T-cell specific IL-2
      expression.

PMID- 15850802
TI  - Efficient killing of CD22+ tumor cells by a humanized diabody-RNase fusion
      protein.
AB  - We report on the generation of a dimeric immunoenzyme capable of simultaneously
      delivering two ribonuclease (RNase) effector domains on one molecule to CD22(+)
      tumor cells. As targeting moiety a diabody derived from the previously humanized
      scFv SGIII with grafted specificity of the murine anti-CD22 mAb RFB4 was
      constructed. Further engineering the interface of this construct (V(L)36(Leu-
      >Tyr)) resulted in a highly robust bivalent molecule that retained the same high
      affinity as the murine mAb RFB4 (K(D)=0.2 nM). A dimeric immunoenzyme comprising
      this diabody and Rana pipiens liver ribonuclease I (rapLRI) was generated,
      expressed as soluble protein in bacteria, and purified to homogeneity. The
      dimeric fusion protein killed several CD22(+) tumor cell lines with high efficacy
      (IC(50)=3-20 nM) and exhibited 9- to 48-fold stronger cytotoxicity than a
      monovalent rapLRI-scFv counterpart. Our results demonstrate that engineering of
      dimeric antibody-ribonuclease fusion proteins can markedly enhance their
      biological efficacy.

PMID- 15850803
TI  - Arachidonic acid inhibits capacitative Ca2+ entry and activates non-capacitative
      Ca2+ entry in cultured astrocytes.
AB  - Arachidonic acid (AA) plays important physiological or pathophysiological roles.
      Here, we show in cultured rat astrocytes that: (i) endothelin-1 or thapsigargin
      (Tg) induces store-depleted activated Ca(2+) entry (CCE), which is inhibited by 2
      aminoethoxydiphenyl borane (2-APB) or La(3+); (ii) AA (10 microM) and other
      unsaturated fatty acids (8,11,14-eicosatrienoic acid and gamma-linoleic acid)
      have an initial inhibitory effect on the CCE, due to AA- or fatty acid-induced
      internal acid load; (iii) after full activation of CCE, AA induces a further
      Ca(2+) influx, which is not inhibited by 2-APB or La(3+), indicating that AA
      activates a second Ca(2+) entry pathway, which coexists with CCE; and (iv) Tg or
      AA activates two independent and co-existing non-selective cation channels and
      the Tg-induced currents are initially inhibited by addition of AA or weak acids.
      A possible pathophysiological effect of the AA-induced [Ca](i) overload is to
      cause delayed cell death in astrocytes.

PMID- 15850804
TI  - Host cell binding of GRA10, a novel, constitutively secreted dense granular
      protein from Toxoplasma gondii.
AB  - Monoclonal antibodies (mAbs) against Toxoplasma gondii, Tg378 and Tg556 clones,
      are specifically observed to localize to the dense granules of tachyzoites by
      immunofluorescence microscopy. mAb Tg556 is directed against GRA3, a previously
      described 30kDa dense granular protein. mAb Tg378 is directed against a novel
      36kDa dense granular protein, which we refer to as GRA10. These are major
      proteins in the excretory/secretory proteins from T. gondii before the parasite's
      entry into host cells, and they are released into the parasitophorous vacuole
      (PV) during or shortly after invasion to be associated with the PV membrane.
      GRA10 binds to the membrane of the host cells regardless of its anchorage
      dependence or -independence. The cDNA sequence encoding GRA10 was determined by
      screening a T. gondii cDNA expression library with mAb Tg378. The deduced amino
      acid sequence of GRA10 consists of a polypeptide of 364 amino acids, and it has
      no significant homology to any other known proteins. The sequence contains amino
      terminal signal peptides and two potential transmembrane domains in the middle of
      sequence that are not near the carboxy terminus. GRA10 has a RGD motif between
      the two potential transmembrane domains.

PMID- 15850805
TI  - Amantadine inhibits hepatitis A virus internal ribosomal entry site-mediated
      translation in human hepatoma cells.
AB  - The effect of six drugs (amantadine, glycyrrhizin, ribavirin, ursodeoxycholic
      acid, alcohol, and IFN) on HAV RNA translation from the HAV internal ribosomal
      entry site (IRES) was investigated using a bicistronic reporter construct
      containing HAV IRES as intragenic spacer. Huh-7 cells and derivatives were
      transfected with in vitro transcripts, and the reporter gene activity was
      determined. IFN suppressed both cap-dependent and HAV IRES-dependent translation,
      while amantadine specifically inhibited HAV IRES-dependent translation. In
      contrast to IFN, by reporter assay, amantadine did not activate the interferon
      stimulated response element (ISRE) or interferon gamma-activated sequence (GAS)
      associated pathways. Immunoblot analysis revealed that amantadine had no effect
      on PKR and on IFN-regulatory factor-1 (IRF-1) expression. These findings
      demonstrated a novel antiviral effect of amantadine against HAV with or without
      HCV infection.

PMID- 15850806
TI  - Identification and characterization of the retinoic acid response elements in the
      human RIG1 gene promoter.
AB  - The expression of retinoic acid-induced gene 1 (RIG1), a class II tumor
      suppressor gene, is induced in cells treated with retinoids. RIG1 has been shown
      to express ubiquitously and the increased expression of this gene appears to
      suppress cell proliferation. Recent studies also demonstrated that this gene may
      play an important role in cell differentiation and the progression of cancer. In
      spite of the remarkable regulatory role of this protein, the molecular mechanism
      of RIG1 expression induced by retinoids remains to be clarified. The present
      study was designed to study the molecular mechanism underlying the all-trans
      retinoic acid (atRA)-mediated induction of RIG1 gene expression. Polymerase chain
      reaction was used to generate a total of 10 luciferase constructs that contain
      various fragments of the RIG1 5'-genomic region. These constructs were then
      transfected into human gastric cancer SC-M1 and breast cancer T47D cells for
      transactivation analysis. atRA exhibited a significant induction in luciferase
      activity only through the -4910/-5509 fragment of the 5'-genomic region of RIG1
      gene relative to the translation initiation site. Further analysis of this
      promoter fragment indicated that the primary atRA response region is located in
      between -5048 and -5403 of the RIG1 gene. Within this region, a direct repeat
      sequence with five nucleotide spacing, 5'-TGACCTctattTGCCCT-3' (DR5, -5243/
      5259), and an inverted repeat sequence with six nucleotide spacing, 5'
      AGGCCAtggtaaTGGCCT-3' (IR6, -5323/-5340), were identified. Deletion and mutation
      of the DR5, but not the IR6 element, abolished the atRA-mediated activity.
      Electrophoretic mobility shift assays with nuclear extract from atRA-treated
      cells indicated the binding of retinoic acid receptor (RAR) and retinoid X
      receptor (RXR) heterodimers specifically to this response element. In addition to
      the functional DR5, the region contains many other potential sequence elements
      that are required to maximize the atRA-mediated induction. Taken together, we
      have identified and characterized the functional atRA response element that is
      responsible for the atRA-mediated induction of RIG1 gene.

PMID- 15850807
TI  - Sphingosine 1-phosphate inhibits migration and RANTES production in human
      bronchial smooth muscle cells.
AB  - Sphingosine 1-phosphate (S1P), a bioactive lipid mediator, has been shown to be
      increased in bronchoalveolar lavage fluid after allergen challenge in asthmatic
      patients. Here, we examined S1P actions and their intracellular signalings in
      cultured human bronchial smooth muscle cells (BSMCs). Expression of mRNAs of
      three subtypes of S1P receptors, including S1P(1), S1P(2), and S1P(3), was
      detected in BSMCs, and exposure of the cells to S1P inhibited platelet-derived
      growth factor (PDGF)-induced migration and tumor necrosis factor-alpha-induced
      RANTES production. S1P also inhibited PDGF-induced Rac1 activation, and dominant
      negative Rac1 inhibited PDGF-induced migration. On the other hand, dominant
      negative Galpha(q) attenuated the S1P-induced inhibition of RANTES production.
      Finally, an S1P(2)-selective antagonist, JTE-013, suppressed the S1P-induced
      inhibition of migration response and RANTES production. These results suggest
      that S1P attenuates cell migration by inhibiting a Rac1-dependent signaling
      pathway and decreases RANTES production by stimulating a Galpha(q)-dependent
      mechanism both possibly through the S1P(2) receptors.

PMID- 15850808
TI  - Increased BNip3 and decreased mutant p53 in cisplatin-sensitive PDT-resistant
      HT29 cells.
AB  - We have reported previously the isolation of three photodynamic therapy (PDT)
      resistant human colon carcinoma HT29 cell lines that show increased expression of
      the Hsp27 and BNip3 protein and a decreased expression of the mutant p53 protein
      compared to parental HT29 cells. Since mutant p53 and increased expression of
      Hsp27 have been associated with resistance to various chemotherapeutic agents,
      whereas BNip3 is a potent inducer of apoptosis, we were interested in determining
      whether these PDT-resistant cells were cross-resistant to other cytotoxic agents.
      We report here that the PDT-resistant HT29 cell lines showed a significant
      increase in cisplatin sensitivity and an increase in both spontaneous and
      cisplatin-induced apoptosis compared to parental HT29 cells. In addition, the
      cisplatin sensitivity of the PDT-resistant HT29 variants and several other clonal
      variants of HT29 cells correlated with increased BNip3 and decreased mutant p53
      protein levels, but not Hsp27 protein levels.

PMID- 15850809
TI  - ATP-binding motifs play key roles in Krp1p, kinesin-related protein 1, function
      for bi-polar growth control in fission yeast.
AB  - Kinesin is a microtubule-based motor protein with various functions related to
      the cell growth and division. It has been reported that Krp1p, kinesin-related
      protein 1, which belongs to the kinesin heavy chain superfamily, localizes on
      microtubules and may play an important role in cytokinesis. However, the function
      of Krp1p has not been fully elucidated. In this study, we overexpressed an intact
      form and three different mutant forms of Krp1p in fission yeast constructed by
      site-directed mutagenesis in two ATP-binding motifs or by truncation of the
      leucine zipper-like motif (LZiP). We observed hyper-extended microtubules and the
      aberrant nuclear shape in Krp1p-overexpressed fission yeast. As a functional
      consequence, a point mutation of ATP-binding domain 1 (G89E) in Krp1p reversed
      the effect of Krp1p overexpression in fission yeast, whereas the specific
      mutation in ATP-binding domain 2 (G238E) resulted in the altered cell polarity.
      Additionally, truncation of the leucine zipper-like domain (LZiP) at the C
      terminal of Krp1p showed a normal nuclear division. Taken together, we suggest
      that krp1p is involved in regulation of cell-polarized growth through ATP-binding
      motifs in fission yeast.

PMID- 15850810
TI  - Identification of a novel cell-cycle-induced MCM family protein MCM9.
AB  - The minichromosome maintenance (MCM) proteins are essential for DNA replication
      initiation and elongation in eukaryotes. In mammalian cells, MCM2-MCM7 complexes
      are believed to unwind DNA during chromosomal DNA replication. Here we identified
      a novel MCM family gene, MCM9, by using bioinformatics. Human, mouse, and rat
      MCM9 showed approximately 90-91% total-amino acid identity. MCM9 showed 24-31%
      total-amino acid identity with MCM2-MCM8 protein. Phylogenetic analysis on MCM
      family members revealed that MCM9 was most closely related to MCM8. Human, mouse,
      and rat MCM9 gene, consisting of 7, 8, and 7 exons, was mapped to 6q22.1-22.33,
      10B3, and 20q11, respectively. We identified transcription factor E2F-binding
      motifs in the vicinity of the transcription start site among human, mouse, and
      rat MCM9 gene. MCM9 mRNA was upregulated by transcription factor E2E1 and serum
      stimulation in NIH3T3 cells.

PMID- 15850811
TI  - Characterization of genes encoding metal tolerance proteins isolated from
      Nicotiana glauca and Nicotiana tabacum.
AB  - We have isolated a metal tolerance protein (MTP) gene, NgMTP1, from Nicotiana
      glauca (a potential phytoremediator plant) and two MTP genes, NtMTP1a and
      NtMTP1b, from Nicotiana tabacum. These three genes shared approximately 95%
      homology at the amino acid level. Heterologous expression of any of these three
      genes complemented Zn and Co tolerance in yeast mutants to a similar extent. In
      yeast, these proteins were shown to be located to vacuole membrane. These results
      suggest that the three MTPs operate by sequestering Zn and Co into vacuoles,
      thereby reducing the toxicity of these metals.

PMID- 15850812
TI  - Serpiginous choroiditis.
AB  - Serpiginous choroiditis is a rare, usually bilateral, chronic, progressive,
      recurrent inflammation of the choroid, retinal pigment epithelium, and
      choriocapillaris of unknown etiology. Based on clinical presentation, it can be
      classified into 1) peripapillary, 2) macular, and 3) ampiginous types. The
      clinical course, regardless of the presentation, is progressive with multiple
      recurrences leading to potentially significant visual loss. Visual outcome is
      directly related to the involvement of the para-fovea and fovea by the lesions or
      secondary choroidal neovascularization. The histological findings of the lesions
      are atrophy of the choriocapillaris, retinal pigment epithelium and photoreceptor
      cells, and moderate diffuse lymphocytic infiltrates throughout the choroid.
      Multiple etiologies including autoimmunity, infection, vasculopathy, and
      degeneration were proposed but none is well supported by clinical and laboratory
      evidence. Fluorescein and indocyanine green angiography have been useful in the
      assessment of the extent and the activity of lesions. Due to the insidious and
      progressive clinical course, an assessment of treatment outcomes needs long term
      follow-up. Currently, treatment with immunosuppressive and alkylating agents have
      shown possible efficacy in small case series. Larger clinical studies and
      interventional trials are required to further our understanding of the
      pathogenesis, etiology, and for the evaluation of treatment strategies.

PMID- 15850813
TI  - Considerations of glaucoma in patients undergoing corneal refractive surgery.
AB  - Glaucoma patients present a unique set of challenges to physicians performing
      corneal refractive surgery. Corneal thickness, which is modified during corneal
      refractive surgery, plays an important role in monitoring glaucoma patients
      because of its effect on the measured intraocular pressure. Patients undergo a
      transient but significant rise in intraocular pressure during the laser-assisted
      in situ keratomileusis (LASIK) procedure with risk of further optic nerve damage
      or retinal vein occlusion. Glaucoma patients with filtering blebs are also at
      risk of damage to the bleb by the suction ring. Steroids, typically used after
      refractive surgery, can increase intraocular pressure in steroid responders,
      which is more prevalent among glaucoma patients. Flap interface fluid after
      LASIK, causing an artificially low pressure reading and masking an elevated
      pressure has been reported. The refractive surgeon's awareness of these potential
      complications and challenges will better prepare them for proper management of
      glaucoma patients who request corneal refractive surgery.

PMID- 15850814
TI  - Computer vision syndrome: a review.
AB  - As computers become part of our everyday life, more and more people are
      experiencing a variety of ocular symptoms related to computer use. These include
      eyestrain, tired eyes, irritation, redness, blurred vision, and double vision,
      collectively referred to as computer vision syndrome. This article describes both
      the characteristics and treatment modalities that are available at this time.
      Computer vision syndrome symptoms may be the cause of ocular (ocular-surface
      abnormalities or accommodative spasms) and/or extraocular (ergonomic) etiologies.
      However, the major contributor to computer vision syndrome symptoms by far
      appears to be dry eye. The visual effects of various display characteristics such
      as lighting, glare, display quality, refresh rates, and radiation are also
      discussed. Treatment requires a multidirectional approach combining ocular
      therapy with adjustment of the workstation. Proper lighting, anti-glare filters,
      ergonomic positioning of computer monitor and regular work breaks may help
      improve visual comfort. Lubricating eye drops and special computer glasses help
      relieve ocular surface-related symptoms. More work needs to be done to
      specifically define the processes that cause computer vision syndrome and to
      develop and improve effective treatments that successfully address these causes.

PMID- 15850815
TI  - Quality of life in patients with age-related macular degeneration: impact of the
      condition and benefits of treatment.
AB  - Age-related macular degeneration (AMD) is a chronic, progressive, degenerative
      disease of the macula and is the leading cause of central vision loss among
      elderly people in the western world. Traditionally, clinical studies of AMD have
      described the impact of AMD, and treatments for AMD, in terms of the patient's
      visual acuity. However, visual acuity alone does not provide information about a
      patient's perception of his or her quality of life. Researchers have used a
      variety of instruments to measure quality of life. Several studies have shown
      that AMD can severely impair quality of life and that increasing vision loss is
      associated with increasing impairment of quality of life and frequently causes
      depression. Interestingly, patients with only one eye affected may become more
      depressed than those with both eyes affected, possibly because of uncertainty
      surrounding future vision loss in patients with one eye affected and a greater
      acceptance of the condition in those with both eyes affected. Studies also have
      provided some information on the possible quality of life benefits of therapy for
      AMD. By incorporating measurements of quality of life into the design of future
      prospective studies, clinical researchers may be able to obtain more
      comprehensive data on the impact of AMD on patients and the relative benefits of
      different therapies.

PMID- 15850816
TI  - Sex hormone receptors in the human eye.
AB  - Dissimilarities in ocular physiopathology exist between human males and females.
      These differences can be observed in the lacrimal and other eye-associated
      glands, the ocular surface, the crystalline lens, and the retinochoroid
      complexes. Literature on the subject revealed that because of sex steroid hormone
      (estrogen, progesterone, and androgen) actions, various physiological conditions,
      such as age, menstrual cycles, pregnancy, and menopause or andropause, where the
      hormone milieu changes, affect vision. Well-designed scientific studies are
      lacking on the subject, although such studies hold much potential value. This
      review analyzes the relatively new area of hormones and vision.

PMID- 15850817
TI  - Foggy vision.
AB  - A 53-year-old man with history of "foggy vision" was referred for neuro
      ophthalmic consultation. His examination showed a right homonymous hemianopia
      detected with automated perimetry. Brain magnetic resonance imaging showed
      extensive enhancement of the structures in the sellar region and patchy meningeal
      enhancement. Blood workup was unremarkable. He eventually had bronchoscopy, which
      confirmed the diagnosis of sarcoidosis.

PMID- 15850818
TI  - Chronic anticholinergic administration and Alzheimer disease.

PMID- 15850819
TI  - The pineal eye of the tuatara.

PMID- 15850821
TI  - Human ether-a-go-go related gene (HERG): a chemist's perspective.

PMID- 15850822
TI  - Fluorescence-based assays.

PMID- 15850823
TI  - Selective and combined neurokinin receptor antagonists.

PMID- 15850824
TI  - Muscarinic receptor subtype pharmacology and physiology.

PMID- 15850825
TI  - The transcription factor NF-kappaB as drug target.

PMID- 15850826
TI  - Recent advances in the search for newer antimalarial agents.

PMID- 15850827
TI  - The discovery of the CCR5 receptor antagonist, UK-427,857, a new agent for the
      treatment of HIV infection and AIDS.

PMID- 15850828
TI  - Granulocyte and granulocyte-macrophage colony-stimulating factors in allografts:
      uses, misuses, misconceptions, and future applications.
AB  - Despite more than 10 years experience using growth factors after allogeneic stem
      cell transplantation (ASCT), their state in this has not been elucidated. Most
      studies show that they accelerate myeloid recovery, regardless of whether they
      are instituted on day 0 or day 10 after transplant. However, this does not
      correlate with an improvement in the outcome. One disadvantage is that
      granulocyte colony-stimulating factor (G-CSF) prophylaxis is associated with
      slower platelet engraftment due to an increase in platelet aggregation. There is
      also no agreement as regards the value of G-CSF given as prophylaxis after ASCT,
      the effects on graft-vs-host disease (GVHD), and the survival rate. A large
      retrospective study from Europe showed that patients with acute leukemia who
      received bone marrow from HLA-identical siblings and were treated with G-CSF ran
      a higher risk of acute and chronic GVHD and transplant-related mortality, while
      the survival and the leukemia-free survival rates were reduced. In contrast, a
      meta-analysis of 18 small studies showed no evidence of an increase in acute and
      chronic GVHD, using G-CSF as prophylaxis after ASCT. Two studies from the Center
      for International Blood and Marrow Transplant Research showed contradictory data.
      When G-CSF is given to the recipient as prophylaxis, the levels of soluble
      interleukin-2 receptor-alpha increase, which aggravates GVHD. When it is given to
      the donor, G-CSF polarizes T cells to produce T-helper cell-2 cytokines, which
      reduce GVHD after transplantation. G-CSF has no effect on relapse. Available
      findings suggest that there is no indication to use G-CSF as prophylaxis after
      ASCT.

PMID- 15850829
TI  - Leukocyte-platelet interaction in patients with essential thrombocythemia and
      polycythemia vera.
AB  - OBJECTIVE: Circulating polymorphonuclear leukocyte (PMN) activation occurs in
      patients with essential thrombocythemia (ET) and polycythemia vera (PV). We want
      to define whether this phenomenon plays a role in the formation of circulating
      PMN-platelet aggregates in these conditions. METHODS: In 80 patients (46 ET and
      34 PV) and 50 control subjects, we conducted a flow cytometric analysis to
      evaluate the levels of PMN-platelet aggregates (defined as the percentage of
      CD11b-positive PMN coexpressing a platelet-specific marker, i.e., CD42b or CD62P)
      and the levels of activated PMN and activated platelets. In addition, the in
      vitro PMN-platelet aggregate formation in response to N-formyl-methionyl-leucyl
      phenylalanine (f-MLP)-induced activation of PMN was studied. RESULTS:
      Significantly high PMN-platelet aggregates in ET and PV patients were found and
      were associated with increased PMN surface CD11b and surface platelet CD62P
      expression. In vitro f-MLP stimulation upregulated PMN-CD11b expression and
      simultaneously increased CD11b/CD42b and CD11b/CD62P aggregates, without
      affecting platelet surface antigens. In ET patients receiving aspirin, the
      increments in f-MLP-induced PMN-CD11b and in PMN-platelet aggregates were
      significantly lower versus ET subjects not treated with aspirin. CONCLUSION: Our
      data show that in ET and PV patients PMN activation plays an important role in
      increasing circulating PMN-platelet aggregates and suggest that aspirin treatment
      may decrease their formation.

PMID- 15850830
TI  - Hypoxia-inducible factor-1 drives the motility of the erythroid progenitor cell
      line, UT-7/Epo, via autocrine motility factor.
AB  - OBJECTIVE: It is well known that hypoxic stress strongly enhances erythropoiesis,
      but the effect of hypoxia on erythroid progenitors has not been examined
      precisely. In the present study, using the erythropoietin-dependent cell line UT
      7/Epo, which has characteristics of erythroid progenitors, we investigated a
      novel role of hypoxia in erythropoiesis. METHODS: UT-7/Epo and four other
      hematopoietic and lymphoid cell lines (HL-60, THP-1, Raji, and CEM) were cultured
      in 20%, 5%, or 1% O2. Morphology was observed under a phase-contrast microscope.
      Cell motility was evaluated using the Transwell migration assay. An analysis of
      the protein level of hypoxia-inducible factor-1 (HIF-1) alpha and autocrine
      motility factor (AMF) was conducted using Western blotting and
      immunocytochemistry, respectively. Reverse transcription polymerase chain
      reaction was performed to evaluate the expression of AMF mRNA. Human bone marrow
      stromal cells were used in cocultures with UT-7/Epo. Apoptosis of UT-7/Epo was
      examined by immunocytochemistry using an antiactive form of caspase 3 antibody.
      RESULTS: Among the five cell lines, UT-7/Epo exhibited active pseudopodial
      extension in hypoxia (1% O2), and cell motility was increased. HL-60, THP-1,
      Raji, and CEM did not show an increase in cell motility even in 1% O2. In
      addition, expression of the alpha-subunit of HIF-1 was activated by hypoxia, and
      expression of the mRNA and protein of AMF induced by HIF-1, increasing cell
      motility, was promoted. The addition of an HIF-1 inhibitor, cadmium chloride
      (CdCl2), or alpha-ketoglutarate (2-oxoglutarate) decreased the AMF mRNA
      expression, and an AMF inhibitor, erythrose 4-phosphate, decreased the cell
      motility. When UT-7/Epo was cocultured with human bone marrow-derived stromal
      cells that significantly inhibit the apoptosis of UT-7/Epo, the migration of UT
      7/Epo under the stromal cells (pseudoemperipolesis) was increased in hypoxia.
      CONCLUSION: Under hypoxic conditions, erythroid progenitors may exhibit active
      migration in the bone marrow and the opportunity for contact with stromal cells
      increases, inhibiting apoptosis.

PMID- 15850831
TI  - Telomere length and telomerase activity in the BCR-ABL-transformed murine Pro-B
      cell line BaF3 is unaffected by treatment with imatinib.
AB  - OBJECTIVE: Imatinib mesylate is a novel tyrosine kinase inhibitor used for the
      treatment of Philadelphia chromosome positive (Ph+) leukemia and other
      malignancies. In previous studies, we found significant telomere shortening in
      Ph+ cells from patients with chronic myeloid leukemia (CML). Interestingly,
      imatinib treatment was found to lead to a normalization of previously shortened
      telomere length in CML patients. Based on recent reports demonstrating that c-ABL
      phosphorylates hTERT and thereby inhibits hTERT activity, a direct effect of
      imatinib on hTERT activity leading to telomere elongation in BCR-ABL-positive
      cells has been proposed by others. Such an effect could be of potential
      importance for telomere maintenance in Ph+ cells by facilitating clonal selection
      and progression of the disease to blast crisis. METHODS: We investigated the
      impact of imatinib on telomere length and telomerase activity of the interleukin
      3 (IL-3)-dependent murine pro-B cell line BaF3 and the BCR-ABL-positive, IL-3
      independent transfectant BaF3p185 in vitro. RESULTS: When BaF3 and BaF3p185 cells
      were treated with imatinib (the latter being rescued with IL-3), no effect on
      either telomerase activity or telomere length was observed. These findings can be
      explained by the cytoplasmatic localization of BCR-ABL found in BaF3p185 as
      compared to the nuclear localization of telomerase (and c-ABL). CONCLUSION: As
      opposed to recent reports for c-ABL, we do not see evidence for a functional
      interaction between BCR-ABL and hTERT in this model system arguing against
      imatinib-mediated upregulation of hTERT as a crucial factor for clonal selection
      and disease progression of CML.

PMID- 15850832
TI  - Role of protein kinase C-delta (PKC-delta) in the generation of the effects of
      IFN-alpha in chronic myelogenous leukemia cells.
AB  - OBJECTIVE: The mechanisms by which interferon alpha (IFN-alpha) induces
      antileukemic responses in chronic myelogenous leukemia (CML) cells are not known.
      We examined whether a member of the protein kinase C (PKC) family of proteins,
      PKC-delta, is activated during treatment of BCR-ABL cells with IFN-alpha and
      participates in the induction of interferon responses. METHODS: Immunoblots and
      immune complex kinase assays were performed to study the phosphorylation and
      activation of PKC-delta in response to IFN-alpha in CML-derived cell lines. The
      effects of pharmacological inhibition of PKC-delta on the suppressive effects of
      IFN-alpha on leukemic CFU-GM progenitors from CML patients were assessed by
      clonogenic assays in methylcellulose. RESULTS: IFN-alpha treatment of the
      sensitive CML-derived KT-1 cell line resulted in phosphorylation of PKC-delta and
      activation of its kinase domain. Such phosphorylation/activation of PKC-delta was
      required for phosphorylation of Stat1 on serine 727, as inhibition of PKC-delta
      activity blocked the IFN-alpha-dependent serine phosphorylation of Stat1 and IFN
      alpha-inducible gene transcription. IFN-alpha treatment strongly inhibited
      leukemic CFU-GM progenitor colony formation from bone marrow or peripheral blood
      of patients with CML, and such inhibition was reversed by concomitant treatment
      of the cells with the PKC-delta pharmacologic inhibitor rottlerin. CONCLUSION:
      Taken altogether, our data demonstrate that PKC-delta plays a critical role in
      Type I IFN signaling in BCR-ABL expressing cells, acting as a serine kinase for
      Stat1, to regulate transcriptional activation of interferon-regulated genes and
      induction of antileukemic responses.

PMID- 15850833
TI  - Diverse effects of the Notch ligands Jagged1 and Delta1 on the growth and
      differentiation of primary acute myeloblastic leukemia cells.
AB  - OBJECTIVE: Notch signaling plays a role in regulating the self-renewal and
      differentiation of hematopoietic progenitors. Since acute myeloblastic leukemia
      (AML) originates from dysregulated hematopoietic progenitors, the Notch system
      may be involved in the abnormal growth. We previously reported that AML cells
      express Notch proteins. In this study, we examined the effects of recombinant
      human Notch ligand proteins, Jagged1 and Delta1, on the growth and
      differentiation of primary AML cells. MATERIALS AND METHODS: AML cells separated
      from blood from 12 patients were cultured in wells coated with Jagged1, Delta1,
      or control IgG. The short-term growth was evaluated using a colorimetric assay.
      The self-renewal capacity was evaluated by the clonogenic cells recovered, which
      were obtained via a colony assay involving cells cultured with the ligands or
      control IgG. Differentiation was evaluated by the morphology of the cultured
      cells and flow cytometric analysis. RESULTS: The ligand stimulation caused three
      types of response in the short-term growth of the primary AML cells, namely,
      promotion, suppression, or no significant effect. The self-renewal capacity was
      suppressed or not significantly affected by the ligands, even in cells showing
      short-term growth promotion. The ligand stimulation altered blast cells into
      macrophage-like cells from their morphology and increased the expression of
      differentiation markers such as CD13 or CD14 in some samples. CONCLUSIONS: The
      Notch ligands had diverse effects on the short-term growth of primary AML cells.
      The ligands did not promote the self-renewal capacity of any of the cells
      examined and instead tended to induce differentiation under the conditions used.

PMID- 15850834
TI  - Critical roles of Raf/MEK/ERK and PI3K/AKT signaling and inactivation of p38 MAP
      kinase in the differentiation and survival of monocyte-derived immature dendritic
      cells.
AB  - OBJECTIVE: The aim of this study is to investigate the signaling pathways and
      their roles in the differentiation of immature monocyte-derived dendritic cells
      (MoDCs). METHODS: MoDCs were generated from peripheral blood monocytes (PBMCs)
      using the standard protocols. Various kinase inhibitors, including SB203580,
      PD98059, and LY294002 and Wortmannin, or p38 activator were added at the
      beginning of the cultures. After 7 days of culture, immature MoDCs were harvested
      and analyzed for their surface expression of relevant molecules and the fraction
      of apoptotic cells by flow cytometry. Western blots were used to analyze mitogen
      activated protein kinase (MAPK), NF-kappaB, Raf, mitogen-induced extracellular
      kinase (MEK), and AKT expression by cultured cells. NF-kappaB was also analyzed
      by electrophoretic mobility shift assay. Allogeneic MLR was used to examine the
      capacity of MoDCs to activate allogeneic T cells. RESULTS: The present study
      shows that the differentiation of immature MoDCs was accompanied by
      phosphorylation of AKT, Raf, MEK, extracellular signal-related kinase (ERK), and
      NF-kappaB activity. Inhibiting PI3K or MEK retarded the differentiation of
      immature MoDCs and induced apoptosis in 10 to 30% of the cultured cells, while
      inhibiting both PI3K and MEK resulted in apoptosis in 70% of the cells.
      Surprisingly, inhibiting p38 enhanced the phosphorylation of ERK and NF-kappaB
      activity and led to an enhanced upregulation, compared with control cells, of
      expression of dendritic cell (DC)-related adhesion and costimulatory molecules
      and antigen presentation capacity. CONCLUSIONS: Our results indicate that the
      Raf/MEK/ERK and PI3K/AKT signaling pathways play critical roles in the
      differentiation and survival of immature MoDCs. Moreover, this study also
      demonstrates that activated p38 is detrimental to the differentiation of immature
      MoDCs.

PMID- 15850835
TI  - Cytokine production and hematopoiesis supporting activity of cord blood-derived
      unrestricted somatic stem cells.
AB  - OBJECTIVE: Cytokine production and hematopoiesis-supporting stromal activity of
      cord blood (CB)-derived unrestricted somatic stem cells (USSC) in comparison to
      bone marrow mesenchymal stem cells (BMMSC) and hematopoietic progenitor expansion
      solely driven by recombinant cytokines were assessed. METHODS: USSC generation
      was initiated from fresh and cryopreserved CB. Cytokine production by USSC and
      BMMSC was determined qualitatively by cytokine mRNA expression array analyses or
      quantitatively by Multiplex or ELISA analyses. To evaluate hematopoiesis
      supporting activity, CB CD34+ cells were expanded in cocultures with USSC and
      BMMSC or in the presence of Flt3-L, SCF, and TPO. Expansion of CD34+ cells, total
      cells, colony-forming cells (CFC), and LTC-IC were determined after 1, 2, 3, and
      4 weeks of culture. RESULTS: USSC constitutively produced SCF, LIF, TGF-1beta, M
      CSF, GM-CSF, VEGF, IL-1beta, IL-6, IL-8, IL-11, IL-12, IL-15, SDF-1alpha, and
      HGF. When USSC were stimulated with IL-1beta, G-CSF was released. Production of
      SCF and LIF were significantly higher in USSC compared to BMMSC. At 1, 2, 3, and
      4 weeks, cocultivation of CD34+ cells on the USSC layer resulted in a 14.6-fold
      +/- 1.1-fold, 110.1-fold +/- 17.9-fold, 151.8-fold +/- 39.7-fold, and 183.6-fold
      +/- 40.4-fold amplification of total cells and in a 30.6-fold +/- 4.4-fold, 101.4
      fold +/- 27.5-fold, 64.7-fold +/- 15.8-fold, and 29.4-fold +/- 3.1-fold
      amplification of CFC, respectively. LTC-IC expansion at 1 and 2 weeks was, with
      2.0-fold +/- 0.1-fold and 2.5-fold +/- 0.3-fold, significantly higher for USSC
      than BMMSC (1.1-fold +/- 0.03-fold and 1.1-fold +/- 0.1-fold), but declined after
      day 21. Transwell cocultures of USSC did not significantly alter total cell or
      CFC expansion. CONCLUSIONS: USSC produce functionally significant amounts of
      hematopoiesis-supporting cytokines and are superior to BMMSC in expansion of
      CD34+ cells from CB. USSC is therefore a suitable candidate for stroma-driven ex
      vivo expansion of hematopoietic CB cells for short-term reconstitution.

PMID- 15850836
TI  - A point mutation affecting an SP1 binding site in the promoter of the
      ferrochelatase gene impairs gene transcription and causes erythropoietic
      protoporphyria.
AB  - OBJECTIVE: Clinical manifestation of erythropoietic protoporphyria (EPP) results
      from coinheritance of a mutated allele and a wild-type low-expressed allele of
      the ferrochelatase (FECH) gene. Currently, up to 90 different mutations affecting
      the coding region or splicing junctions of the FECH gene have been identified.
      Despite the high molecular heterogeneity, no functional mutations have been
      previously reported in the promoter region. The weaker allele expression has been
      controversially associated to the presence of different intragenic polymorphisms.
      METHODS: We applied a two-step screening strategy using denaturing gradient gel
      electrophoresis followed by direct sequencing in order to rapidly identify FECH
      gene mutations in Italian EPP patients. We identified two unrelated subjects
      showing a normal FECH coding region but a single G>C base substitution at
      position -250 in the FECH promoter and the -251G, IVS1-23T, and IVS3-48C
      polymorphisms in trans to the substitution. To investigate the effect of the 
      250G>C mutation on protein binding to the FECH promoter, we conducted electro
      mobility shift assay (EMSA) and supershift analysis. To determine its effect on
      the transcriptional activity, K562 and Jurkat cell lines were transiently
      transfected. RESULTS: EMSA showed that the -250G>C mutation results in the loss
      of an SP1 binding site, and transient transfection assays demonstrated that such
      mutation strongly impairs promoter activity. Moreover, we showed that the -251A>G
      polymorphism, although unable to affect SP1 binding, displays a significant
      reduction in the transcriptional activity of the promoter. CONCLUSION: This is
      the first report of a mutation in the FECH promoter affecting binding of a
      transcription factor and causing EPP phenotype.

PMID- 15850837
TI  - Quiescence of hematopoietic stem cells and maintenance of the stem cell pool is
      not dependent on TGF-beta signaling in vivo.
AB  - OBJECTIVE: Maintained quiescence of hematopoietic stem cells (HSCs) is of
      critical importance to prevent premature exhaustion of the stem cell pool under
      conditions of hematopoietic stress. The growth inhibitory cytokine transforming
      growth factor beta (TGF-beta) has been shown to play a critical role in
      maintaining quiescence of HSCs in vitro. Here, we have used conditional knockout
      mice for the TGF-beta type I receptor (TbetaRI) to ask whether the naturally
      quiescent state of HSCs in vivo is dependent on TGF-beta signaling and thus
      whether TGF-beta serves as a protective factor for the stem cell pool during
      conditions of stress. METHODS: TbetaRI null and control bone marrow chimeras were
      subjected to repeated treatments with the cell cycle-specific cytotoxic drug 5
      fluorouracil (5-FU) and surviving HSCs were assayed by competitive
      transplantation experiments. Exhaustion of stem cells was provoked by serially
      transplanting TGF-beta signaling-deficient as well as normal BM cells into
      lethally irradiated recipients, which were monitored for survival. RESULTS:
      Surprisingly, we found that TGF-beta receptor-deficient HSCs have similar
      susceptibility, compared to controls, to repeated 5-FU treatments, indicative of
      normally maintained quiescence in these cells. Likewise, hematopoietic failure
      occurred at similar stages in serially transplanted recipients of TbetaRI null
      and control BM, respectively, demonstrating normal consumption of the stem cell
      pool during hematopoietic stress. CONCLUSIONS: These findings clearly demonstrate
      that, despite a key role in vitro, TGF-beta does not provide the necessary signal
      that induces the quiescent state of HSCs and maintains the stem cell pool in
      vivo.

PMID- 15850838
TI  - Flow cytometric evaluation of circulating CD34+ cell counts and apoptotic rate in
      children with acquired aplastic anemia and myelodysplasia.
AB  - OBJECTIVE: Identification of a rapid and noninvasive test for the follow-up of
      aplastic anemia (AA) patients during immunosuppressive therapy (IST) to evaluate
      its functional effect on hematopoietic progenitors (HPC) and for early detection
      of progression to myelodysplasia or relapse. MATERIALS AND METHODS: Absolute
      count and apoptotic rate (AR) of peripheral blood (PB) CD34+ cells were evaluated
      by three-color flow cytometry for CD45, CD34, and annexin V in cord blood (CB),
      normal children, and adults, as well as in pediatric patients with AA at
      diagnosis and during IST, Fanconi anemia (FA), chronic immune cytopenia, and
      refractory anemia with excess blasts (RAEB). RESULTS: In normal subjects, the AR
      of PB CD34+ cells showed a progressive increase (p < 0.05), while their counts
      decreased (p < 0.05) from birth to adulthood. In very severe AA (vSAA) and severe
      AA (SAA) at diagnosis, the AR was 91.6% +/- 2.8%, higher than controls (p <
      0.05), and PB CD34+ cell count was 2.6 +/- 2.4/microL. In FA patients, the PB
      CD34+ AR was again significantly increased (54.2% +/- 13.7%) with an absolute
      count of 3.7 +/- 1.2/microL. Conversely, in RAEB the AR was 11.7% +/- 3.5% and
      the absolute count 85.1 +/- 48.2/microL (p < 0.05). Chronic immune cytopenias did
      not significantly differ from controls. CONCLUSIONS: Flow cytometry evaluation of
      PB CD34+ AR and counts is a noninvasive and feasible first-step method for the
      differentiation of AA and myelodysplasia (MDS), and it might be useful for
      monitoring AA during IST to secure the early detection of relapse or
      transformation to MDS.

PMID- 15850839
TI  - Mesenchymal stem cells remain of host origin even a long time after allogeneic
      peripheral blood stem cell or bone marrow transplantation.
AB  - OBJECTIVE: Plasticity of hematopoietic stem cells (HSC) has gained major interest
      in stem cell research. In order to investigate whether HSC may differentiate into
      mesenchymal stem cells (MSC), we assessed chimerism in peripheral blood (PB),
      mononuclear cell fractions (MNC) of bone marrow, and MSC derived from bone marrow
      (BM) from 27 up to 4225 days after allogeneic transplantation. PATIENTS AND
      METHODS: We applied fluorescence in situ hybridization using X/Y gene probes in
      sex-mismatched and STR-PCR in sex-matched patients. MSC could have been generated
      in 27 of 55 bone marrow samples derived from 20 patients. Fifteen patients
      received peripheral blood stem cell transplants (PBSCT), including CD34-selected
      PBSCT in two. Five patients received bone marrow. RESULTS: While all patients had
      chimerism in PB and MNC of the BM, in all but one patient BM-derived MSC were of
      recipient origin. This single patient showed reproducibly MSC of donor origin in
      a frequency of 1% after having received a CD34-selected PBSCT. Looking at graft
      collections, MSCs were easily generated from BM specimens, while no MSC could be
      derived from PBSC samples. CONCLUSION: Even though HSC have been found to
      differentiate into a variety of nonhematological cell types, they usually do not
      differentiate into MSC after allogeneic transplantation.

PMID- 15850841
TI  - Cushing's syndrome from bedside to bench and back: a historical perspective.
AB  - This article focuses on the development of Cushing's syndrome as a clinical
      entity, a process that has moved from bedside to bench and back again.

PMID- 15850842
TI  - Hypothalamic-pituitary-adrenocortical axis regulation.
AB  - As befits a system essential for survival, neuroendocrine regulation of the
      hypothalamic--pituitary--adrenocortical (HPA) axis is characterized by tight
      control as well as plasticity. Stimulus-specific afferents code for specific
      hypothalamic corticotropin (ACTH) secretagogues, which have combinatorial effects
      on ACTH secretion, resulting in a glucocorticoid response that is tailored to
      stimulus intensity. Chronic stress-induced stimulation of HPA activity alters
      ACTH secretagogue expression and hypothalamic afferent activity to maintain
      adrenocortical responsiveness. Rigorous control of circadian HPA activity
      optimizes the balance between beneficial and adverse effects of glucocorticoids
      (largely mediated by glucocorticoid receptors) by minimizing circadian nadir
      glucocorticoid secretion (an effect mediated by mineralocorticoid receptors). HPA
      activity also is controlled by other glucocorticoid-regulated factors, such as
      immune and metabolic status. Dysregulation of these control mechanisms is likely
      to contribute to a variety of diseases.

PMID- 15850843
TI  - Adrenal corticosteroid biosynthesis, metabolism, and action.
AB  - Adrenal corticosteroids are essential for life, and an appreciation of the
      mechanisms underpinning their synthesis, secretion, and mode of action in normal
      physiology is essential if the physician is to diagnose and treat patients who
      have Cushing's syndromes effectively. In each case, there have been clinically
      significant advances in the knowledge base over recent years, notably in the
      understanding of steroidogenesis, cortisol action, and metabolism. This article
      describes corticosteroid biosynthesis, metabolism, and action.

PMID- 15850844
TI  - Glucocorticoid resistance and hypersensitivity.
AB  - This article emphasizes the disorders caused by mutations and polymorphisms of
      the alpha form of the glucocorticoid receptor. These disorders usually present
      with increased circulating cortisol concentrations and must be distinguished from
      Cushing's syndrome, because the therapies are markedly different. The other
      disorders present with clinical features limited to a specific organ system.
      Although they illustrate important physiologic and pathophysiologic principles,
      they usually are not confused with Cushing's syndrome.

PMID- 15850845
TI  - The metabolic syndrome and cardiovascular risk in Cushing's syndrome.
AB  - Cushing's syndrome (CS) is characterized by a series of systemic complications
      that increase cardiovascular risk and cause severe atherosclerotic damage that
      develops in parallel with an acquired metabolic syndrome. Short-term remission
      from hypercortisolism improves metabolic and vascular damages, but long-term
      remission from CS seems to be associated with similar or worse metabolic and
      vascular damage, probably because of persistent abdominal obesity or insulin
      resistance years after normalization of cortisol secretion. Study results suggest
      that an increased cardiovascular risk also may persist in patients who undergo
      treatment with exogenous glucocorticoids after therapy withdrawal. Considering
      the many patients subjected to corticosteroid treatment, this could be of great
      clinical relevance and should be investigated thoroughly.

PMID- 15850846
TI  - Osteoporosis associated with excess glucocorticoids.
AB  - Excess glucocorticoids, whether endogenous or exogenous, can cause osteoporosis
      and fractures. Even low doses of oral glucocorticoids and mild endogenous
      hypercortisolism may be associated with bone loss. Patients treated with
      glucocorticoids, however, often are not evaluated and treated for this problem.
      Patients on chronic glucocorticoids or initiating these drugs should have their
      bone density measured and appropriate laboratory studies. They should be treated
      with adequate calcium and vitamin D, and antiresorptive therapy (particularly
      bisphosphonates) should be considered.

PMID- 15850847
TI  - Cognitive function and cerebral assessment in patients who have Cushing's
      syndrome.
AB  - Cushing's syndrome (CS) is a relevant model to better understand the effects of
      glucocorticoid (GC) excess on the human brain. The importance of GC excess on the
      central nervous system is highlighted by the high prevalence of neuropsychiatric
      disorders such as depression and cognitive impairment in patients who have CS. In
      addition, there is a high incidence of apparent diffuse loss of brain volume in
      patients who have CS. Recent studies indicate at least partial reversibility of
      these abnormalities following correction of hypercortisolism.

PMID- 15850848
TI  - Exogenous Cushing's syndrome and glucocorticoid withdrawal.
AB  - Glucocorticoid therapy in various forms is extremely common for a wide range of
      inflammatory, autoimmune, and neoplastic disorders. It is therefore important for
      the physician to be aware of the possibility of both iatrogenic and factitious
      Cushing's syndrome. Although most common with oral therapy, it is also important
      to be alert to the fact that all forms of glucocorticoid delivery have the
      potential to cause Cushing's syndrome. Withdrawal from chronic glucocorticoid
      therapy presents significant challenges. These include the possibility of adrenal
      insufficiency after discontinuation of steroid therapy, recurrence of underlying
      disease as the glucocorticoid is being withdrawn, and the possibility of steroid
      withdrawal symptoms. Nonetheless, with patience and persistence, a reasonable
      approach to withdrawal of glucocorticoid therapy can be achieved.

PMID- 15850849
TI  - Screening and diagnosis of Cushing's syndrome.
AB  - Screening studies in high-risk populations have suggested that Cushing's syndrome
      is more common than previously appreciated. Patients who have specific signs and
      symptoms or clinical diagnoses known to be associated with hypercortisolism
      should be considered for screening. The measurement of late-night salivary
      cortisol provides the most sensitive method for screening, and urine-free
      cortisol and low-dose dexamethasone suppression testing may be used for
      confirmation of the diagnosis of endogenous hypercortisolism

PMID- 15850850
TI  - Differential diagnosis and imaging in Cushing's syndrome.
AB  - Establishing the cause of Cushing's syndrome (CS) is one of the most challenging
      processes in clinical endocrinology. Biochemical testing, including measurement
      of plasma adrenocorticotropin (ACTH), high-dose dexamethasone suppression, and
      corticotropin-releasing hormone stimulation testing, is integral to the
      differential diagnosis. No existing test has sufficient diagnostic accuracy when
      used alone, however. The adjunctive use of focused imaging, including CT, MRI,
      and nuclear imaging modalities, often can provide a diagnosis. In patients with
      ACTH-dependent CS, bilateral inferior petrosal sinus sampling can facilitate a
      diagnosis in those with discrepant clinical features, biochemistry, or imaging.
      This article focuses on current biochemical and radiologic strategies for the
      differential diagnosis of CS.

PMID- 15850851
TI  - Subclinical Cushing's syndrome in adrenal incidentalomas.
AB  - This article reviews the available evidence on subclinical Cushing's syndrome in
      patients who have adrenal incidentalomas. The authors' aim is to present up-to
      date information on the most relevant issues of subclinical Cushing's syndrome by
      addressing the many uncertainties and controversies surrounding this ill-defined
      endocrine condition.

PMID- 15850852
TI  - Bilateral adrenal Cushing's syndrome: macronodular adrenal hyperplasia and
      primary pigmented nodular adrenocortical disease.
AB  - Corticotropin (ACTH)-independent bilateral macronodular adrenal hyperplasia
      (AIMAH) and primary pigmented nodular adrenocortical disease (PPNAD) are
      responsible for approximately 10% of adrenal Cushing's syndrome. AIMAH also can
      be present as subclinical bilateral incidentalomas in sporadic or familial forms.
      Diverse aberrant hormone receptors have been found to be implicated in the
      regulation of steroidogenesis and pathophysiology of AIMAH. PPNAD can be found
      alone or in the context of Carney complex, a multiple endocrine neoplasia
      syndrome. Additionally, it can be secondary to mutations of type 1 alpha
      regulatory subunit of cAMP-dependent protein kinase A (PRKARIA). Strategies for
      the investigation and treatment of AIMAH and PPNAD are discussed.

PMID- 15850853
TI  - Pituitary surgery and postoperative management in Cushing's disease.
AB  - Transsphenoidal pituitary surgery is the therapy for most Cushing's disease
      patients. This article describes the surgical technique, efficacy, perioperative
      management, and complications associated with this procedure. Numerous
      biochemical tests of cortisol status have been studied for the evaluation of the
      postoperative patient. Factors that predict postoperative remission and future
      relapse of Cushing's disease are addressed. Secondary interventions for
      persistent or recurrent disease include repeat transsphenoidal resection,
      pituitary radiation, medical therapy, and bilateral adrenalectomy

PMID- 15850854
TI  - Pituitary radiotherapy.
AB  - This article includes general comments about pituitary radiation, outcomes in
      patients who have Cushing's disease and adverse effects of treatment.

PMID- 15850855
TI  - Laparoscopic adrenalectomy for patients who have Cushing's syndrome.
AB  - Laparoscopic adrenalectomy is one of the most significant advances in the past 20
      years for treating adrenal disorders. When compared with open adrenalectomy,
      laparoscopic adrenalectomy is equally safe, effective, and curative; it is more
      successful in shortening hospitalization and convalescence and has less long-term
      morbidity. The laparoscopic approach is the procedure of choice for the surgical
      management of cortisol-producing adenomas and for patients who have corticotropin
      (ACTH)-dependent Cushing's syndrome for whom surgery failed to remove the source
      of ACTH. The keys to successful laparoscopic adrenalectomy are appropriate
      patient selection, knowledge of anatomy, delicate tissue handling, meticulous
      hemostasis, and experience with the technique of laparoscopic adrenalectomy.

PMID- 15850856
TI  - Breast cancer prevention in community clinics: will low-income Latina patients
      participate in clinical trials?
AB  - BACKGROUND: Latinas have low rates of participation in breast cancer prevention
      trials. We evaluated the feasibility and effectiveness of a randomized trial of
      brief counseling and print materials compared to print materials alone to
      increase intent to participate in a breast cancer prevention trial. METHODS: We
      enrolled 450 women Spanish-speaking women from three urban community primary care
      clinics. The outcome was intent, defined as might, probably, or definitely would
      enroll in the trial. We also examined results using a more stringent definition
      restricted to probably and definitely intend to participate. RESULTS: The trial
      was feasible within these busy clinics, and 96% of women agreed to participate.
      The level of breast cancer knowledge was fairly high (66% correct answers), but
      understanding about clinical trials was lower (40.5% correct answers). Using the
      less stringent criteria for intent, 72% of women stated that they intended to
      enroll in the STAR trial if eligible, but rates of intent decreased to 52% with
      framing that included medication side effects and 45% if uterine cancer was
      mentioned (P < 0.01 for trend). Using the more stringent definition, slightly
      fewer than half of the women indicated an interest in participating, with the
      same trend towards decreasing intent with increasing presentation of side
      effects. The intervention was only effective using the less stringent definition
      and if no side effects were mentioned (77% intent vs. 67% in the intervention and
      control groups, respectively, P = 0.03). Intention was independently associated
      with greater worry about breast cancer and younger age, but not acculturation or
      knowledge. CONCLUSIONS: Latina women are interested in participating in clinical
      trials to prevent breast cancer, although interest declines with increasing
      discussion of side effects. Unfortunately, brief education only increased rates
      of intention using the least stringent definition and when no side effects were
      presented in framing the question. Future work should focus on qualitative
      research to understand the theoretical foundations of preventive health behaviors
      in this population.

PMID- 15850857
TI  - Testing a culturally appropriate, theory-based intervention to improve colorectal
      cancer screening among Native Hawaiians.
AB  - BACKGROUND: We tested an intervention based on social learning theory (SLT) to
      improve colorectal cancer (CRC) screening among Native Hawaiians, a group with
      low CRC screening rates. METHOD: Sixteen Hawaiian civic clubs agreed to
      randomization. Eight control clubs received a culturally targeted presentation, a
      free Fecal Occult Blood Test (FOBT), and a reminder call. Eight experimental
      clubs also received culturally targeted education and free testing; but, in line
      with SLT, education was delivered by a Native Hawaiian physician and Native
      Hawaiian CRC survivor, and members received an FOBT demo, were challenged to
      involve a family member in screening, and were telephoned multiple times to
      address change-related emotions and barriers. RESULTS: One hundred twenty-one
      members age 50 and older from 16 clubs participated. At the club level, screening
      rates were modestly increased in four experimental clubs and six control clubs.
      Surprisingly, 64% of participants reported being up to date with CRC screening at
      baseline. Only 13 individuals (five in experimental arm and eight in the control
      arm) were screened for the first time through this intervention, increasing the
      percent screened from 59% to 67% in the experimental group and from 69% to 85% in
      the control group. Although individuals in the experimental arm were more likely
      to rate the intervention as culturally appropriate, both arms realized similar
      and significant gains in CRC knowledge, attitudes, intent, and self-efficacy.
      CONCLUSIONS: For Native Hawaiian individuals belonging to a network of civic
      clubs, an intervention based on SLT delivered by a Native Hawaiian physician and
      CRC survivor was less effective at further increasing compliance than was a
      culturally targeted educational session delivered by a non-Hawaiian nurse. That
      CRC screening compliance was high prior to our intervention suggests that we
      targeted a very health conscious segment of the Native Hawaiian population.
      Future work should focus on underserved segments of this indigenous group.

PMID- 15850858
TI  - Men's experiences of physical exams and cancer screening tests: a qualitative
      study.
AB  - BACKGROUND: American men have lower overall rates of cancer screening than women.
      This study was designed to elicit men's health care experiences and knowledge of
      testicular, prostate, and colorectal cancer (CRC) screening. METHODS: Fifty-three
      men participated in eight physician-led semistructured focus groups in Rhode
      Island and New Hampshire. Four groups (ages 18-35; N = 20) discussed testicular
      cancer screening. Four groups of older men (ages 40-79; N = 33) discussed
      prostate and colorectal cancer screening. RESULTS: Men in this study prefer
      physicians who establish interpersonal relationships with male patients. Lack of
      explanations during physical exams resulted in negative experiences. Men were
      eager to learn more about their health, but commonly complained that they
      received neither appropriate cancer screening nor sufficient explanations from
      their physicians. When PSA screening was offered, discussion was often
      inadequate. Although men expressed interest in participating in the PSA decision,
      sole responsibility for this complex decision was seen as undesirable. These men
      desired more discussion and better sources of health information during medical
      encounters. CONCLUSIONS: Clinician attention to communication, relationship
      building, patient education, and consideration for patient privacy and modesty
      are important for the care of male patients especially with sensitive exams and
      topics important to men's cancer screening.

PMID- 15850859
TI  - Knowledge, attitudes, risk factors, and early detection of cancer relevant to the
      schoolteachers in Izmir, Turkey.
AB  - BACKGROUND: Teachers are the population of interest because of the important role
      they play in education and possibly in prevention of cancer. The purpose of the
      research is to describe knowledge, attitudes, risk factors and early detection
      relevant to cancer of schoolteachers. METHODS: A descriptive survey is conducted
      among 358 schoolteachers who are randomly selected from the eight schools in
      Izmir, Turkey. A self-administered questionnaire is used to investigate their
      knowledge in cancer, risk factors, attitudes, and early detection of cancer.
      RESULTS: Knowledge in cancer and symptoms are assessed using the data collected
      from a series of simple questions. Potential scores ranged from 0 to 15.
      CONCLUSIONS: In the sample, scores are distributed around a mean of 7.43 +/-
      2.87. Risk factors and early detection associated with cancer are generally low.

PMID- 15850860
TI  - Health status, health behaviors, and acculturation factors associated with
      overweight and obesity in Latinos from a community and agricultural labor camp
      survey.
AB  - BACKGROUND: U.S. Latino adults have experienced an 80% increase in obesity in the
      last decade. METHODS: A cross-sectional survey of 18-64-year-old Latino women (N
      = 380) and men (N = 335) from a community sample, and men (N = 186) from an
      agricultural labor camp sample in Monterey County, California, provided data on
      correlates of obesity. RESULTS: In the community and labor camp samples,
      prevalences of chronic disease risk factors (high blood pressure and cholesterol,
      diabetes) were 1.5-7 times higher in the heaviest compared with the leanest
      weight groups. Higher acculturation (generational status, years lived in the
      United States) was the strongest correlate of obesity (measured by BMI) in the
      community sample (P < 0.001), followed by less exercise and poorer diet (P values
      < 0.05). Women who exercised <2.5 h/week, watched TV regularly, ate chips/fried
      snacks, and ate no fruit the previous day were 45 lbs heavier than women with
      healthier habits. Men who did not exercise, rarely trimmed fat from meat, and ate
      fried foods the previous day were 16 lbs heavier than men with healthier habits.
      Discussions with health care providers about diet/exercise were associated with
      more accurate weight perception and more weight loss attempts in obese
      participants in both samples. CONCLUSIONS: The associations of acculturation,
      exercise, and diet to BMI implicate societal as well as individual contributors
      to obesity among U.S. Latinos.

PMID- 15850861
TI  - Epidemiology and prevention of tobacco use in Tunisia: a review.
AB  - INTRODUCTION: This paper describes trends in tobacco sales and smoking prevalence
      in the Tunisian population, it estimates the consequences of smoking on mortality
      of this population and discusses anti-tobacco actions: educational actions,
      legislative measures, and price increases. DATA SOURCES: Sales data were
      collected from the Tunisia tobacco monopoly, smoking prevalence data from surveys
      conducted by several institutes, and numbers of deaths by causes have been
      estimated from WHO for 1998 year. RESULTS: Tobacco sales increased from 4.96 g
      per adult per day in 1981 to 6.3 g in 1993, then decreased widely. The proportion
      of smokers was 30% in 1996, 55% among men versus 5.6% among women. Among 17 to 24
      years old young adults, the proportion of smokers was 29.2% in 1994 (50% among
      men versus 3.9% among women). Mortality attributable to tobacco in Tunisia has
      been estimated to 6430 deaths in 1997 (5580 among men versus 850 among women).
      These deaths represent 22% of total male deaths and 4% of female ones. Anti
      tobacco measures have been reinforced by the enactment of anti tobacco law.
      CONCLUSION: Proportion of young smokers remaining high, it is expected that the
      consequences of tobacco addiction in Tunisia in term of mortality will be even
      heavier in the next two decades if efficient anti tobacco actions are not
      implemented.

PMID- 15850862
TI  - Determinants of adolescent bicycle use for transportation and snacking behavior.
AB  - BACKGROUND: The prevalence of obesity has reached epidemic proportions in many
      countries and is largely due to behavioral factors that disrupt the energy
      balance. The purpose of the study was to test how well our conceptual model,
      combining features from the Theory of Planned Behavior and the Theory of Triadic
      Influence, explained two behaviors related to the energy balance, namely bicycle
      use for transportation and snacking behavior in a Dutch adolescent sample.
      METHODS: Data was gathered in an 1997 cross-sectional sample of adolescents (n =
      3,859; mean age 14.8 years SD = 1.6) on snacking behavior, bicycle use,
      demographics, and potential environmental, cognitive and psychological
      determinants. Data was analyzed using bivariate correlations, multiple linear and
      binary logistic regression analyses. RESULTS: Less snacking behavior was
      associated with female gender and a more positive intention, a more positive
      attitude, and stronger perceived behavioral control towards restricting snacking.
      Students who used their bicycle for transportation were more likely to attend
      secondary education, to be native Dutch, to go to school in a less-urbanized
      city, to be younger, had a more positive intention and perceived stronger
      behavioral control and subjective norm towards bicycle use. CONCLUSIONS: The
      inclusion of environmental factors increased our understanding of bicycle use for
      transportation and snacking behavior in adolescents. The environmental factors
      are suggested to be taken into account in interventions aimed at changing these
      behaviors in more healthy directions.

PMID- 15850863
TI  - Lifestyles and health-related quality of life in Japanese school children: a
      cross-sectional study.
AB  - BACKGROUND: Lifestyles are associated with physical and mental health status, as
      well as health-related quality of life (QOL) in adults. There is little
      information about relation between lifestyles and QOL in children. This study
      aims to examine the correlation among Japanese children. METHODS: Subjects were
      from the Toyama Birth Cohort Study, a prospective, longitudinal survey of
      children born between 1989 and 1990 in Toyama Prefecture, Japan. When children
      were 12-13 years in 2002, a cross-sectional questionnaire-based survey was
      administered. The questionnaire designed to measure lifestyles included questions
      on eating, physical activity, sleep, and other factors. For QOL measurement, a
      validated Japanese version of the COOP Charts was used. Data from 7,887 children
      were available and logistic regression analyses were used. RESULTS: Children with
      undesirable lifestyles, such as skipping breakfast, less participation in
      physical activity, longer television viewing, and later bedtime, were more likely
      to have poor QOL in domains of physical fitness, feelings, overall health, and
      quality of life. These correlations were independent of sex, BMI, social
      background, and somatic symptoms. CONCLUSIONS: Undesirable lifestyles are
      positively associated with impaired QOL among children. Further understanding of
      these relationships will facilitate the development of interventions to help
      children with poor QOL.

PMID- 15850864
TI  - Smoking reduction in a population-based cohort.
AB  - OBJECTIVE: To describe the factors associated with smoking reduction in a
      population-based cohort study in Cornella de Llobregat (Barcelona, Spain).
      MATERIAL AND METHODS: We used data from the Cornella Health Interview Survey
      Follow-up Study (n = 2,500). We included for the analysis those subjects who
      declared to be daily smokers at baseline (1994) and continued smoking after eight
      years of follow-up (n = 234). We considered as operational definition of
      reduction to reduce > or = 10 cigarettes/day. We calculated the relative risk
      (RR) of smoking reduction vs. maintain or increase tobacco consumption and 95%
      confidence intervals (CI) by means of a Breslow-Cox regression model. RESULTS:
      The average reduction on number of cigarettes among subjects who reduced their
      tobacco consumption was similar in men and women (13 cigarettes/day). The
      consumption intensity and self-perceived health are the characteristics
      associated with reduction: smoking reduction was associated with being a smoker >
      20 cigarettes/day (RR = 3.25; 95% CI: 1.69-6.25) and individuals who declared
      having a suboptimal health showed a 3-fold risk of reducing smoking (RR = 3.13;
      95% CI: 1.52-6.43). CONCLUSION: Heavy smokers and smokers with poor health are
      those smokers more likely to reduce their tobacco consumption. Specific actions
      targeting them could lead to increase reduction and even smoking cessation.

PMID- 15850865
TI  - Immune status to poliovirus among immigrant workers in Israel.
AB  - BACKGROUND: An essential part of the progress towards the global eradication of
      poliomyelitis is the ongoing evaluation of populations immunity. Migration of
      unregistered individuals poses a challenge to such estimations. Moreover,
      partially immunized immigrants might enlarge immunity gaps and facilitate polio
      outbreaks in their destination countries. OBJECTIVES: To study the level of
      immunity to polio in adult foreign workers in Israel. METHODS: Foreign workers (n
      = 145) from the Philippines, India, and Western Africa were tested for
      neutralizing antibodies against three IPV strains and an outbreak-associated wild
      virus. Demographic and immunization data were collected by questionnaires.
      RESULTS: Seropositivity rates and geometric mean titers (GMTs) for the Mahoney
      (type 1), MEF (type 2), and Saukett (type 3) poliovirus strains and the wild
      poliovirus type 1 strain were 99.3% (GMT--233.8), 98.6% (GMT--268.5), 99.3% (GMT-
      89.4), and 99.3% (GMT--139.5), respectively. Higher GMTs were associated with
      parenthood and older age. African individuals had significantly higher GMTs for
      the Saukett strain, compared with individuals from the Philippines and India.
      CONCLUSIONS: Our results indicate a high level of immunity among foreign workers.
      More serosurveys are indicated in the future in order to monitor the level of
      immunity in residents in Israel.

PMID- 15850866
TI  - Male involvement in cardiovascular preventive healthcare in two rural Costa Rican
      communities.
AB  - BACKGROUND: Gender differences in health system usage can lead to differences in
      the incidence of morbidity and mortality. We conducted a pilot screening targeted
      towards men to evaluate gender differences in cardiovascular disease risk factor
      detection and time since last clinic visit. METHODS: Three evening sessions in
      two communities screened 148 people, mean age 47.7 years. Height, weight, body
      mass index, blood pressure, blood glucose, and total cholesterol were measured. A
      questionnaire on past medical history was administered. Participants with
      elevated measurements were referred to appropriate care. RESULTS: Men accounted
      for 60.1% of those screened; 65.5% of the group was overweight, and 22.3% was
      obese with 42.6% hypertension, 39.2% hypercholesterolemia, and 2.7% high blood
      glucose. Among men aged 35 to 65, 65.2% were overweight, 20.3% obese, 46.4%
      hypertensive, 42.0% hypercholesterolemic, and 1.5% with high blood glucose.
      Within the last 2 years, 53.3% of men and 9.1% of women aged 35 to 65 had not
      visited a doctor (P = 0.004). CONCLUSIONS: A significant portion of those
      screened had elevated cardiovascular disease risk factors. Given that men visited
      doctors significantly less frequently, efforts to involve men in prevention of
      cardiovascular disease within these communities are warranted.

PMID- 15850867
TI  - Are examination findings important in screening for angina in the Malaysian
      patient?
AB  - BACKGROUND: The objective of this study is to look at how well patient history
      and examination findings can be used in screening for angina. METHODS: A total of
      887 records were extracted from the electronic medical record system (EMR) in
      Selayang Hospital, Malaysia. The data was cleaned; 69 possible variables were
      extracted, and univariate and multivariate analyses were performed. RESULTS: From
      the univariate analysis, it was found that 19 variables are significantly
      associated with a diagnosis of angina. However, multiple logistic regression
      reveals that only 11 of these 19 variables are significantly related to a
      diagnosis of angina. Chest pain aggravated by exertion, history of diabetes
      mellitus, and history of heart disease (regardless of whether on treatment or
      not) are significant predictors of angina. Sudden onset chest pain, pain that is
      persistent, pain relieved by other means, pain aggravated by inspiration, and
      findings of rhonchi are important predictors of a diagnosis other than angina.
      The degree of overall accuracy is high at 71.3%. There are eight factors which
      are significant in the univariate analysis but are not significant in the
      multivariate analysis. These are marital status, pain relieved by glyceryl
      trinitrate (GTN), pain relieved by rest, associated nausea, pain aggravated by
      posture, pain aggravated by cough, history of hypertension, and history of
      smoking. CONCLUSIONS: These findings suggest that examination findings do not
      play a significant role in screening for angina.

PMID- 15850868
TI  - A population-based estimate of the prevalence of behavioral risk factors among
      adult cancer survivors and noncancer controls.
AB  - BACKGROUND: Behavioral risk factors have significant biomedical and psychosocial
      effects for cancer survivors. Representative data on the prevalence of a wide
      range of behavioral risk factors among cancer survivors are lacking. METHODS: We
      used data from the 2000 National Health Interview Survey to examine the
      prevalence of smoking, physical inactivity, dietary risk factors, being
      overweight, risky alcohol use, and sun protection behaviors among a sample of
      32,346 adults, 1646 of whom were cancer survivors. RESULTS: With the exception of
      smoking, there were few differences in age-stratified behavioral risk factor
      prevalences between cancer survivors and noncancer controls. Among the cancer
      survivors, there were few differences in behavioral risk factor prevalence rates
      for survivors of different cancers. Exceptions included a high rate of current
      smoking for cervical and uterine cancer survivors. The prevalences of physical
      inactivity, dietary risk factors, and being overweight were relatively high
      across cancer types, whereas the prevalence of risky drinking was particularly
      low. CONCLUSIONS: This study provides benchmark estimates of the prevalence of
      multiple cancer-related behavioral risk factors among U.S. cancer survivors. The
      results reveal considerable opportunities for behavioral risk factor
      interventions among cancer survivors. We discuss implications of the results and
      outline directions for future research.

PMID- 15850869
TI  - A simple lifestyle score predicts survival in healthy elderly men.
AB  - BACKGROUND: Although improvements in life expectancy have been attributed in part
      to the adoption of a more prudent lifestyle, few studies have examined the
      association of lifestyle with survival, using several lifestyle factors
      simultaneously, in a healthy elderly population. METHODS: We investigated the
      association of health related behaviors with mortality in 7989 men aged 65 to 83
      years participating in a population-based trial in Perth, Western Australia, by
      calculating a lifestyle score as a simple tally of how many of eight prudent
      behaviors each individual followed. RESULTS: Invitations to screening produced a
      corrected response of 70.5%. Out of a possible score of 8, 46% of men had a score
      of less than 5. Within 5 years, a total of 703 men (9%) had died from any cause.
      The hazard ratio in men with a low lifestyle score was 1.3 [95% confidence
      interval (CI): 1.1-1.5] compared with men with a score of 5 or more. CONCLUSIONS:
      Lifestyle remains an important predictor of mortality even in old age. Survival
      in older men without a history of cardiovascular disease can potentially be
      enhanced by promoting a healthy lifestyle.

PMID- 15850870
TI  - Context of care or provider training: the impact on preventive screening
      practices.
AB  - BACKGROUND: While MD adherence to U.S. Preventive Services Task Force guidelines
      has been found to be uneven, nurse practitioners (NPs) and their adherence to
      guidelines have not been closely examined. METHODS: A retrospective chart review
      of new patients (n = 1339) in an NP primary health care center, four MD primary
      health care centers, and one private NP practice. Screening and counseling were
      compared for NPs and MDs. RESULTS: When patient populations, resources, and
      administrative policies were similar in the NP and MD primary health care
      centers, NPs were more likely than MDs to perform primary prevention; however,
      MDs were more likely to document the delivery of secondary prevention screening.
      Private practice NPs' performance was more congruent with practice guidelines
      than either NP or MD primary health care center providers. Private practice NPs
      were more likely to perform screening, assessment, and counseling. CONCLUSIONS:
      When context, patient population, and productivity requirements were the same,
      NPs and MDs differed in their use of preventive measures, and not as expected.
      When NPs are not constrained by productivity requirements, and when their patient
      population has more resources and higher expectations, NPs perform better than
      their primary care center counterparts, particularly in secondary prevention and
      assessment and counseling.

PMID- 15850871
TI  - The risk of acute myocardial infarction after stopping drinking.
AB  - BACKGROUND: Subjects at high risk of alcohol-related diseases may benefit from
      alcohol cessation. However, drinkers have a lower risk of acute myocardial
      infarction (AMI) than abstainers, and there is very scanty information on how the
      risk changes after stopping drinking. METHODS: Between 1995 and 1999, we
      administered a structured questionnaire to 507 cases (378 men, 129 women) with a
      first episode of nonfatal AMI and 478 control patients (297 men, 181 women)
      admitted to the same network of hospitals in the greater Milan area for acute
      conditions. RESULTS: Compared to lifelong abstainers, the odds ratio (OR)
      adjusted for age, sex, and several AMI risk factors was 0.56 (95% confidence
      interval [CI] 0.41-0.84) for current and 0.65 (95% CI 0.37-1.15) for former
      drinkers (48 cases and 44 controls). The OR was 2.10 (0.40-11.1) for having
      stopped since 1 year, 0.64 (95% CI 0.19-2.16) for 2-4 years, 0.46 (95% CI 0.18
      1.20) for 5-14 years, and 0.78 (95% CI 0.27-2.27) for > or = 15 years.
      CONCLUSIONS: Although our data are too limited to draw any definite conclusion,
      they suggest that the protection of alcohol drinking against AMI may persist, at
      least in part, for several years after stopping.

PMID- 15850872
TI  - Facilitating practice change: lessons from the STEP-UP clinical trial.
AB  - BACKGROUND: The Study To Enhance Prevention by Understanding Practice (STEP-UP)
      clinical trial (1997-2000) resulted in sustainable increases in preventive
      service delivery in primary care practices. However, the process by which
      practice change can be facilitated has not been well described. METHODS:
      Comparative case studies were conducted of eight STEP-UP practices with the
      largest increases in preventive service delivery rates and compared to seven
      practices with the lowest increases. A multidisciplinary team (research nurse,
      nurse facilitator, physician principal investigator) used an editing analysis
      approach to create individual case studies. Then, using an immersion
      crystallization approach, the team identified pragmatic lessons for people
      working to improve primary care practice, and validated these lessons with a
      participating practice and an additional facilitator. RESULTS: It is not always
      possible to predict which practices will change based on understanding initial
      practice conditions. "Malleable moments" can be identified during which practices
      become open to change. It is important to tie change strategies with existing
      motivations, or to develop new motivation among potential change agents.
      Motivation can be developed by discrepant information that challenges self-image,
      aligning change plans with existing values, or identifying feasible ways of
      responding to outside pressures or internal demands. Instrumental interventions
      (such as office systems, tools, new processes) are useful when motivation to
      change exists, and can build motivation when they meet a perceived need.
      Disruption in previously workable approaches, either by purposeful information
      seeking or unanticipated changes, promotes openness to change. CONCLUSIONS:
      Despite limited ability to predict which practices will change and when,
      understanding practices' initial conditions and evolution can identify
      opportunities to craft individualized approaches to positive change.

PMID- 15850873
TI  - Is social desirability associated with self-reported physical activity?
AB  - BACKGROUND: Physical activity has been considered to be a socially desirable
      behavior that might be overreported because of a social desirability bias. This
      study involved an examination of the possible influence of social desirability on
      self-report measures of physical activity. METHODS: Participants were male and
      female college students (N = 782) who completed the Lie scale of the Eysenck
      Personality Questionnaire (L-scale), Marlowe-Crowne Social Desirability Scale
      (SDS), Godin Leisure-Time Exercise Questionnaire (GLTEQ), and Stanford Usual
      Activity Questionnaire. RESULTS: Scores from the Lie scale were not significantly
      correlated with scores from either the Godin Leisure-Time Exercise Questionnaire
      or the Stanford Usual Activity Questionnaire. With the Social Desirability Scale,
      there were statistically significant, but weak correlations with scores from the
      Godin Leisure-Time Exercise Questionnaire and the Stanford Usual Activity
      Questionnaire. There was no influence of the Lie scale and Social Desirability
      Scale on the magnitude of the correlations between scores from the two measures
      of physical activity. CONCLUSIONS: This study provides minimal evidence of an
      influence of social desirability on scores from two self-report instruments for
      measuring physical activity in young adults.

PMID- 15850874
TI  - Cardiovascular disease risk factors in 6-7-year-old Danish children: the
      Copenhagen School Child Intervention Study.
AB  - OBJECTIVE: To describe population values in cardiovascular disease (CVD) risk
      factors such as blood lipids, fasting insulin and glucose and blood pressure in
      this young age group, and calculate associations to fitness and fatness. METHODS:
      Participants were 369 boys (6.8 +/- 0.4 years) and 327 girls (6.7 +/- 0.4 years)
      from preschool classes in Copenhagen. Peak VO2, blood pressure (BP), fat content
      and anthropometry were determined. A fasting blood sample was analysed for
      insulin, glucose and blood lipids. Physical activity was measured using
      accelerometry. RESULTS: Mean BMI, BP and blood lipids were not different between
      sexes. Fat percentage assessed from skinfolds was higher (21.5% vs. 16.5%) in
      girls than in boys (P < 0.001). Peak VO2 and physical activity were higher in
      boys than in girls (8% and 9%, respectively). Peak VO2 associated to fatness
      independent of body weight (r = 0.41; P < 0.001). Among the CVD risk factors,
      fitness was associated to high-density lipoprotein (HDL) (r = 0.14; P < 0.01) and
      physical activity (r = 0.12; P < 0.01). Fatness assessed by skinfold was
      associated to blood pressure (r = 0.19-0.28; P < 0.001), to fasting glucose (r =
      0.11, P < 0.05) and insulin (r = 0.17; P < 0.001). CONCLUSIONS: Mean BP in 6-7
      year-old Danish children has decreased since 1979 and BMI has increased modestly
      since 1986/1987. The lipid profile was similar compared with data from 1973 and
      1978 in Danish children. Weak relationships were found between CVD risk factors,
      fitness and fatness.

PMID- 15850875
TI  - Pap smear use in California: are we closing the racial/ethnic gap?
AB  - BACKGROUND: Minority women continue to be disproportionately affected by cervical
      cancer. Minority population groups at high risk for cervical cancer may be
      failing to fully comply with screening recommendations. The use of Pap smears
      among women in California was evaluated to identify ethnic groups at higher risk
      for noncompliance with cervical cancer screening. METHODS: Cross-sectional
      analysis of 2001 California Health Interview Survey data. Logistic regression was
      used to assess the independent contribution of race/ethnicity to the use of Pap
      smears. RESULTS: Hispanic (aPR = 1.03, 95% CI 1.02-1.05) and Black (aPR = 1.03,
      95% CI 1.001-1.06) women are more likely to report a Pap smear in the past 3
      years as compared to White women. Asians were the least likely to report cervical
      cancer screening despite a more favorable sociodemographic profile. Screening
      rates varied among Hispanic or Asian subgroups; Mexicans, Vietnamese, Chinese,
      and South Asians are particularly underserved. CONCLUSIONS: In contrast to the
      country as a whole, Hispanic women in California are more likely to report a
      recent Pap smear as compared to White women. However, racial/ethnic disparities
      in Pap smear use persist; Asian women are the least likely to report cervical
      cancer screening as compared to any other group.

PMID- 15850876
TI  - Inequalities in the prevalence of smoking in the European Union: comparing
      education and income.
AB  - BACKGROUND: The aim of the study was to determine whether education or income was
      more strongly related to smoking in the European Union at large, and within the
      individual countries of the EU, at the end of the 1990s. METHODS: We related
      smoking prevalence to education and income level by analyzing cross-sectional
      data on a total of 48,694 men and 52,618 women aged 16 and over from 11 countries
      of the European Union in 1998. RESULTS: Both education and income were related to
      smoking within the European Union at large. After adjustment of the other
      socioeconomic indicator, education remained related to smoking in the EU at
      large, but income only remained so among men. Educational inequalities were
      larger than income-related inequalities among younger and middle-aged men and
      women. Educational inequalities were larger than income-related inequalities
      among men in all individual countries, and among women in Northern Europe. For
      women from Southern European countries, the magnitude of education- and income
      related inequalities was similar. CONCLUSIONS: Education is a strong predictor of
      smoking in Europe. Interventions should aim to prevent addiction to smoking among
      the lower educated, by price policies, school-based programs, and smoking
      cessation support for young adults.

PMID- 15850877
TI  - "Back to sleep": parents compliance with the recommendation on the most
      appropriate sleeping position of infants, Haifa District, Israel, 2001.
AB  - BACKGROUND: In 1993, the Israel Ministry of Health issued a formal recommendation
      to avoid placing healthy infants to sleep in the prone position in order to
      prevent sudden infant death. The objective of the study was to study parents'
      compliance with this recommendation and to identify characteristics of
      noncompliant parents of infants aged less than 6 months old. METHODS: The study
      population consisted of 1912 parents of infants aged 0-12 months who visited the
      Haifa District primary preventive health centers during the study week and
      answered the self-administered questionnaire. RESULTS: 15.6% of infants younger
      than 1 year were placed to sleep in the prone position: 12.4% among infants
      younger than 3 months, and 17.6% among infants 3-6 months old. Surprisingly,
      multiple logistic regression analysis demonstrated that Israeli-born Jewish
      mothers were more likely to place their babies prone than Israeli-born Arab
      mothers or mothers born in the former Soviet Union who had immigrated to Israel
      after 1990. CONCLUSIONS: At-risk behaviors are usually associated with minority
      and immigrant populations. Culture specific and other possible reasons for our
      unusual findings are discussed.

PMID- 15850878
TI  - Long-term maintenance of exercise and healthy eating behaviors in overweight
      adults.
AB  - BACKGROUND: Most people experience weight regain following the termination of a
      weight management program. The failure to maintain changes in diet and exercise
      patterns is a major factor. This study presents 24-month outcomes of a healthy
      lifestyle weight management program designed to promote long-term changes in diet
      and exercise behaviors. METHODS: Overweight and obese adults (n = 144; BMI = 32.5
      +/- 3.8) completed a 6-month clinic-based weight management program and were
      followed for an additional 18 months. Assessments completed at baseline, 6, 12,
      and 24 months included weight, body composition, dietary recalls, self-reported
      physical activity, and mediator variables based on Transtheoretical Model of
      Health Behavior Change. RESULTS: At 24 months, subjects maintained decreases in
      weight, % body fat, caloric intake, % kcal saturated fat, and increases in weekly
      exercise minutes (P < 0.05). Individuals who maintained regular exercise at 24
      months had higher confidence scores and higher use of experiential and behavioral
      processes. Individuals who maintained a healthy diet at 24 months had lower
      temptation scores and higher use of experiential and behavioral processes.
      CONCLUSIONS: A healthy-lifestyle weight management program is successful at
      promoting long-term changes in exercise and dietary behaviors. Individuals who
      actively engage in the maintenance process are more likely to succeed.

PMID- 15850879
TI  - Knowledge and perceived risk of smoking-related conditions: a survey of cigarette
      smokers.
AB  - BACKGROUND: Previous studies suggest that smokers minimize the personal health
      risk of smoking. Smokers may not be aware of the various smoking-related disease
      risks or believe that they are susceptible to them. METHODS: We presented 537
      adult treatment-seeking smokers with a list of 34 medical conditions, of which 25
      were smoking-related conditions, and 9 were nonsmoking-related items. Subjects
      were asked to identify which medical conditions were smoking-related, and to rate
      their perceived risk (using a 7-point Likert scale) of developing various smoking
      related conditions if they continued to smoke. RESULTS: The average percentage of
      knowledge items correct for each disease category included cardiovascular (93%),
      pulmonary (94%), oral health diseases (89%), smoking-related cancers (71%), and
      reproductive risks (44%). Premature death was identified as a risk by 95% of
      smokers yet only 63.5% reported that disability could also result from smoking.
      Knowledge was associated with perceived risk of smoking-related illnesses across
      disease categories. CONCLUSIONS: Knowledge and perceived risk of cardiovascular,
      pulmonary, and oral disease was high among current smokers; knowledge and
      perceived risk of reproductive-related problems, and cancers other than lung
      cancer was much lower. Smokers recognize that smoking may result in premature
      death, but are less likely to acknowledge that smoking could result in a
      disability significantly affecting their quality of life.

PMID- 15850880
TI  - Self-comparison processes, prototypes, and smoking onset among early adolescents.
AB  - BACKGROUND: Research has shown that social images or prototypes of smoking peers
      play a role in adolescents' decisions to start smoking. To devise effective
      prevention measures, specific information is needed about how adolescents
      evaluate characteristics associated with smoker prototypes. Such evaluation is
      assumed to occur through self-comparison processes, that is, 'self-consistency'
      and 'self-enhancement' motivations. This is one of the first studies to examine
      longitudinal relations between both these motivational processes and smoking
      behavior. METHODS: Self-reported data on motivational processes and smoking were
      gathered at two waves (with a 1-year interval) among Dutch adolescents (12-16
      years). Relations between self-comparison processes and willingness to smoke or
      future smoking behavior were tested among a sample of 1938 respondents. RESULTS:
      Smoker prototypes predicted adolescents' smoking onset, particularly those images
      that referred to daily smoking peers as being "cool" or "rebellious."
      Furthermore, self-consistency and self-enhancement motivations predicted smoking
      onset for certain characteristics associated with smoker prototypes. CONCLUSION:
      Evidence for the role of self-consistency and self-enhancement motivations in
      adolescents' smoking onset suggests that smoking prevention projects should
      target both similar and aspiring features associated with the image of smoking
      peers.

PMID- 15850881
TI  - Social-cognitive determinants of vaccination behavior against hepatitis B: an
      assessment among men who have sex with men.
AB  - BACKGROUND: Many individuals who are at risk for infection with the hepatitis B
      virus (HBV), including men who have sex with men (MSM), are not vaccinated. This
      study assessed social-cognitive determinants of obtaining vaccination against
      HBV. METHODS: A targeted survey was conducted among 432 MSM by means of a written
      questionnaire that contained assessments of social-cognitive determinants of
      vaccination behavior derived from the Health Belief Model (HBM) and the Theory of
      Planned Behavior. Vaccination behavior was anonymously linked to questionnaire
      data for which informed consent was obtained. RESULTS: Of the 290 men eligible
      for vaccination, 248 (86%) had obtained vaccination. Multivariate logistic
      regression analysis showed that these men were younger, more often were in a
      steady relationship, and had fewer sex partners. In addition, significant effects
      were also found for central factors proposed by the Health Belief Model. Notably,
      men who obtained vaccination against HBV perceived more personal threat from HBV.
      None of the Theory of Planned Behavior variables were related to obtaining
      vaccination. CONCLUSIONS: Findings suggest that health education interventions
      that address perceived susceptibility and severity are likely to contribute to
      increased uptake of HBV vaccination among MSM. Influencing perceived
      susceptibility in particular is important, more so than increasing perceived
      severity by scare tactics.

PMID- 15850882
TI  - Blood lipid and lipoprotein levels: relationships with educational level and
      region of residence in the French SU.VI.MAX study.
AB  - BACKGROUND: Blood lipid profile of French men and women obtained from the general
      population is not well known. Furthermore, the association between these lipids,
      as a function of other potential risk factors for cardiovascular disease, and
      sociodemographic factors such as age, educational level, and region of residence
      is not well studied in large samples in Europe. METHODS: Data on French healthy
      volunteers, aged between 40 and 65 years for men (n = 5141) and 35 and 65 years
      for women (n = 7876) were obtained from the "Supplementation en Vitamines et
      Mineraux Antioxydants" (SU.VI.MAX) study, a primary prevention trial. Baseline
      blood samples were collected in 1994-1995 and analyzed for cholesterol,
      triglyceride, apolipoproteins (apo)-B and -A1. The results were analyzed
      separately for men and women as a function of age, educational level, and area of
      residence. RESULTS: Overall, blood lipid levels for men and women did not differ
      significantly from those reported in other Western industrialized countries.
      Except for triglyceride in men, all blood lipids were statistically different
      among ages. In women, cholesterol, apo-A1, and apo-B showed a significant
      decrease with educational level. Statistical differences were found in both
      genders between blood lipids and lipoproteins among regions of residence.
      CONCLUSIONS: Even if differences between region of residence were found in blood
      lipid levels, this cannot explain the North-East to South gradient in the
      prevalence of cardiovascular disease in France nor differences between France and
      other industrialized Western countries.

PMID- 15850883
TI  - Cognitive changes in cardiovascular patients following a tailored behavioral
      smoking cessation intervention.
AB  - BACKGROUND: Action aimed at changing smoking behavior to prevent cardiovascular
      patients from further impairing their health is advisable. Cognitive behavioral
      interventions can be effective in this regard since they attempt to influence
      cognitive determinants that presumably lead to smoking cessation. The Minimal
      Intervention Strategy for Cardiology patients (C-MIS) is such an intervention,
      tailored to the patients' readiness to change. Our aim is to investigate whether
      the C-MIS is successful in changing patients' cognitions such as attitudes,
      social influence, self-efficacy and intention to quit during a 1-year period.
      METHODS: Smoking outpatients (N = 315) with cardiovascular disease were included.
      They were randomized and received either Nicotine Replacement Therapy (NRT) or
      NRT + C-MIS. At baseline (T1), sociodemographic and clinical characteristics were
      measured. Cognitions and quitting behavior were assessed at baseline and at four
      follow-up measurements. RESULTS: Comparing treatments, the C-MIS did not affect
      pros of quitting, pros of smoking and social influence. We did find small effects
      of the C-MIS on intention to quit and self-efficacy, although only for higher
      educated patients. CONCLUSION: The C-MIS appears successful in affecting
      intention to quit and self-efficacy abilities, but only for patients with higher
      education levels. Initial positive changes in cognitions may also emerge in a
      medical intervention, such as the provision of NRT.

PMID- 15850884
TI  - Baseline predictors of initiation vs. maintenance of regular mammography use
      among rural women.
AB  - BACKGROUND: Predictors of regular mammography screening over many years have not
      often been examined prospectively. We used data from baseline (1993-1994), first
      (1996-1997), and second follow-up (2000) interviews with 336 White and 314
      African-American rural women in the North Carolina Breast Cancer Screening
      Program to evaluate baseline factors predictive of regular mammography use over 7
      years. METHODS: We defined regular mammography use as a recent mammogram (past 2
      years) at all three interviews. Using binomial and logistic regression models
      adjusted for age, we examined factors associated with initiation (for women
      without prior regular use) and maintenance (for women with prior regular use) of
      mammography. RESULTS: Younger age and White race were predictive of initiation of
      regular mammography use. Physician recommendation was the strongest predictor of
      both initiation and maintenance of regular mammography use. Positive mammography
      attitudes and fewer personal barriers were strongly associated with initiation
      but not with maintenance. CONCLUSIONS: Increased contact with providers and
      greater support for screening mammograms by providers could have an important
      impact on rural women initiating and maintaining regular mammography screening.
      Special efforts are needed to prompt rural African-American women and those over
      age 65 to initiate screening, since once they start they are likely to continue.

PMID- 15850885
TI  - Examining the relationships among built environment, physical activity, and body
      mass index in El Paso, TX.
AB  - OBJECTIVE: The current study examined the relationships among built environment,
      physical activity, and body mass index (BMI) in a primarily Hispanic border
      community in El Paso, TX. METHODS: Data from a 2001 community-wide health survey
      were matched to environmental data using geocoding techniques in ARC VIEW
      software. A total of 996 adults were surveyed by phone and 452 were successfully
      geocoded. RESULTS: The sample was 71% female, 79% Hispanic, 42 +/- 17 years old,
      moderately acculturated, and had socioeconomic status (SES) levels of semi
      skilled workers. Increasing BMI was related to less moderate intensity physical
      activity (P = 0.05), higher SES (P = 0.0003), worse overall health (P = 0.0004),
      and living in areas with greater land-use mix (less residential; P = 0.03). The
      relationship between overall health and BMI was in part mediated by higher
      numbers of barriers to physical activity in those with poor health, which lead to
      a decrease in moderate physical activity. These variables explained 20% of the
      variance in BMI. CONCLUSIONS: This is one of the first studies to find a positive
      relationship between land-use mix and BMI in a predominantly Hispanic, low-income
      community. The positive association between BMI and land-use mix may be due to
      the inclusion of individual SES as a controlling variable in the analyses,
      suggesting that SES may have a differential effect on how the built environment
      influences BMI in low- to moderate-income minority communities.

PMID- 15850886
TI  - Smoking prevention for ethnically diverse adolescents: 2-year outcomes of a
      multicultural, school-based smoking prevention curriculum in Southern California.
AB  - BACKGROUND: Effective school-based curricula are needed to prevent smoking among
      ethnically diverse adolescents. This study evaluated a multicultural smoking
      prevention curriculum in ethnically diverse Southern California middle schools.
      METHODS: Students in 24 middle schools (N = 3157 sixth graders) received the
      multicultural curriculum, a similar curriculum without references to cultural
      issues, or a control condition. Odds ratios for experimentation with smoking over
      a 2-year period were calculated. RESULTS: The multicultural program was
      associated with a lower risk of smoking between sixth and eighth grade, relative
      to the control group. Program effects varied according to the ethnic composition
      of the schools. In schools with predominantly Hispanic populations, the
      multicultural curriculum was more effective than the control, but the standard
      curriculum was not. In schools with predominantly Asian or multicultural
      populations, the standard curriculum was more effective than the control, but the
      multicultural curriculum was not. Analyses stratified by ethnicity within the
      schools revealed that the multicultural curriculum was effective among Hispanic
      students within predominantly Hispanic schools, but not among Hispanic students
      within predominantly Asian/multicultural schools. CONCLUSIONS: Smoking prevention
      for adolescents in culturally diverse school contexts is a challenge. In this
      study, a multicultural curriculum was most effective among Hispanic students in
      predominantly Hispanic schools. Further research is needed to determine the best
      ways to prevent smoking in predominantly Asian and multicultural schools.

PMID- 15850887
TI  - Senior student smoking at school, student characteristics, and smoking onset
      among junior students: a multilevel analysis.
AB  - BACKGROUND: Current research on the etiology of tobacco use has largely focused
      on identifying the influential psychosocial characteristics of individual
      students; the influences of characteristics in the school environment are
      generally ignored. The purpose of this study was to simultaneously examine how
      school and individual student characteristics were related to smoking onset.
      METHOD: Multilevel logistic regression analysis was used to examine how the
      senior student smoking rate at a school and the psychosocial characteristics of
      students were able to differentiate tried-once smokers from experimental smokers
      in a sample of 4850 grade 9, 10, and 11 students from the School Smoking Profile
      (SSP) project. RESULTS: Each 1% increase in smoking rate among high school
      seniors increased the odds that a junior student was an experimental smoker vs. a
      tried-once smoker (OR 1.07, 95% CI 1.03-1.12). A significant contextual
      interaction was identified where the senior student smoking rate at a school
      moderates the negative influence of having close friends who smoke. Influential
      student characteristics were also identified. CONCLUSIONS: The smoking prevalence
      of older students at a school is directly related to smoking onset among younger
      students at that school. Prevention programs should target schools that put
      students at-risk.

PMID- 15850888
TI  - Do parents' perceptions of risks protect children engaged in farm work?
AB  - BACKGROUND: The purpose was to describe farm parents' perceptions of risks on
      their farms and determine if these perceptions were associated with (1) using of
      the North American Guidelines for Children's Agricultural Tasks (NAGCAT) and (2)
      making NAGCAT-recommended changes to enhance the safety of farm work for their
      children. METHODS: This is a secondary analysis of data collected by telephone
      interview during a randomized trial that involved 450 farms in the United States
      and Canada. RESULTS: While 81% of farm parents perceived farming to be more
      dangerous than other occupations, only 66% of those parents felt that it was more
      dangerous for children to work on a farm than at other work. Furthermore, risk
      perception scores were only weakly associated with parents' use of NAGCAT and
      making NAGCAT-recommended safety changes. CONCLUSION: Even with voluntary safety
      guidelines in hand and the general perception of farming as a dangerous
      occupation, many farm parents were not actively using NAGCAT to reduce the
      exposure of their children to hazardous farm work. Together with the continuing
      morbidity and mortality among farm children, this suggests that voluntary
      guidelines alone may not be sufficient to protect children working on farms.

PMID- 15850889
TI  - Implementation and outcomes of recommended folic acid supplementation in Mexican
      American women with prior neural tube defect-affected pregnancies.
AB  - BACKGROUND: Upon discovering an NTD incidence rate of 27/10,000 in a Texas border
      county, the Texas Department of Health initiated folic acid intervention for
      prevention of recurrent NTDs in this predominantly Mexican-American population.
      This paper describes compliance of this population with USPHS folic acid
      recommendations and the impact of supplementation on pregnancy outcomes. METHODS:
      Based upon information from active surveillance, field teams personally contacted
      women having NTD-affected pregnancies to enroll them in FA intervention.
      Enrollees were provided FA at home visits at 3-month intervals throughout the
      project. RESULTS: Of 405 women identified with NTD-affected pregnancies, 299
      (73.8%) enrolled in the intervention. One hundred ninety-three pregnancies
      occurred among 138 women. FA supplementation of 0.4 mg/day or more occurred
      during the last month preconception in 161 (83.4%) of the 193 pregnancies. No
      NTDs were detected in the 130 livebirths to women who received supplementation
      nor were NTDs detected in the 23 supplemented women who experienced pregnancy
      loss. CONCLUSIONS: Supplementation was successful in preventing recurrent NTDs in
      Mexican-American women.

PMID- 15850890
TI  - Differences in food intake and exercise by smoking status in adolescents.
AB  - BACKGROUND: Smoking, diet, and lack of exercise are the top preventable causes of
      death in the United States. Some 23% of high school students currently smoke and
      many teens do not meet Healthy People 2010 standards for healthy eating or
      physical activity. This study examined the relationship between smoking and the
      consumption of fruit, vegetables, milk/dairy products and the frequency of
      exercise in 10,635 Virginia youth. METHODS: Survey data were collected from
      middle school (MS; n = 8022) and high school (HS; n = 2613) adolescents
      participating in youth tobacco prevention/cessation programs. Data were analyzed
      using chi-square bivariate tests and multivariate regression models. RESULTS:
      Smokers were significantly less likely than nonsmokers to exercise > or = 3x week
      and to consume > or = 1 serving/day of vegetables or milk/dairy products. This
      was more evident in high school than middle school students and in females
      compared to males. In both HS and MS, a dose-response relationship was detected
      with higher level smoking associated with lower frequency of eating specified
      food and exercise. CONCLUSIONS: Smoking is associated with compromised intake of
      healthy food and exercise. To decrease incident cases of chronic disease later in
      life, new tailored, innovative interventions are needed that address multiple
      health behaviors in youth.

PMID- 15850891
TI  - Increasing mammography screening among low-income African American women with
      limited access to health information.
AB  - BACKGROUND: Previous research showed low-income African American women with
      limited access to breast screening information through mass media to have a low
      likelihood of obtaining screening. This report describes a controlled evaluation
      of a component of a community-based breast screening promotion program focused on
      increasing screening among low-income African American women. METHODS: A direct
      contact screening promotion component tailored to the needs of low-income African
      American women was conducted between 1990 and 1997 in one of two matched Florida
      study areas. Before and after assessments of breast screening, behavior and
      psychosocial mediators of screening were examined using logistic regression
      analyses for 1201 women with differing levels of exposure to media information
      about breast screening. RESULTS: Recent/repeat mammography use increased
      significantly in the program area for women with limited access to media
      information, although there was no significant program impact on hypothesized
      psychosocial mediators of screening. CONCLUSIONS: The program led to increased
      mammography use among low-income African Americans having limited access to
      screening information through the media. For these women, using direct contact to
      deliver educational messages and facilitation of access to services may be the
      best method available to promote regular mammography.

PMID- 15850892
TI  - Statewide evaluation of a tobacco cessation curriculum for pharmacy students.
AB  - BACKGROUND: Previous studies suggest that healthcare professionals are
      inadequately trained to treat tobacco use and dependence. Because even brief
      interventions from clinicians improve patient quit rates, widespread
      implementation of effective tobacco cessation training programs for health
      professional students is needed. METHODS: Pharmacy students received 7-8 h of
      comprehensive tobacco cessation training. Participants completed pre- and post
      program surveys assessing perceived overall abilities for cessation counseling,
      skills for key facets of cessation counseling (Ask, Advise, Assess, Assist,
      Arrange), and self-efficacy for counseling. RESULTS: A total of 493 students
      (82.3%) completed linkable pre- and post-training evaluations. Self-reported
      abilities, measured on a five-point scale, increased significantly from 1.89 +/-
      0.89 to 3.53 +/- 0.72 (P < 0.001). Twenty-two percent of students rated their
      overall counseling abilities as good, very good, or excellent before the training
      versus 94% of students after the training. Eighty-seven percent of students
      indicated the training will increase the number of patients that they counsel;
      97% believed it will increase the quality of their cessation counseling.
      CONCLUSIONS: Comprehensive training significantly improved pharmacy students'
      perceived confidence and ability to provide tobacco cessation counseling. The
      curriculum is applicable to other health professional training programs and
      currently is being used to train pharmacy, medical, nursing, and dental students.

PMID- 15850893
TI  - Impact of a food-based approach to improve iron nutrition of at-risk infants in
      northern Canada.
AB  - BACKGROUND: We evaluated the impact of a food-based approach in promoting iron
      rich complementary feeding for mothers with infants at-risk for iron deficiency
      anemia (IDA). METHODS: A repeat cross-sectional design was used to assess the
      impact of communication strategies to disseminate key messages promoting iron
      rich complementary food. Two groups of mothers with infants, aged 7-10 months, at
      Time 1 (n = 32; response rate = 64%) and Time 2 (n = 22; response rate = 48%)
      were interviewed. Main outcome variables were infants' total iron and
      complementary food iron intakes measured by two 24-h recalls. RESULTS:
      Complementary food iron intake increased between Time 1 (3.2 +/- 0.8 mg) and Time
      2 (4.4 +/- 1.1 mg) (P < 0.05). The estimated prevalence of inadequacy was 56%
      (95% CI = 38%, 74%) for infants at Time 1 and 41% (95% CI = 20%, 62%) for infants
      at Time 2; however, this difference was not statistically significant.
      CONCLUSIONS: A food-based approach, promoted in a community with infants at-risk
      for IDA, can positively contribute to improved intake of complementary food iron
      as well as provide a sustainable and relevant prevention strategy.

PMID- 15850894
TI  - An approach to the prevention of anxiety-related disorders based on evolutionary
      medicine.
AB  - Anxiety-related disorders are among the more common ailments of modern societies.
      Presumably, their prevalence is partly due to environmental factors, which
      suggests that anxiety may be one of the health problems that are aggravated by
      discords (adverse mismatches) between the present way of life and what our genes
      are adapted to. Consequently, it may be possible to find preventive measures by
      using the perspective of evolutionary medicine. I shall argue that the prevalence
      of anxiety-related problems reflects that the nerve circuitry and endocrine
      activity associated with the fear function have developed beyond normal.
      Moreover, that this expansion is due to excessive or abnormal triggering,
      particularly at an early age. Possible discords that may be responsible, such as
      present child care practices, will be discussed.

PMID- 15850896
TI  - A remembrance of Rupert K. A. Schmidt-Ullrich, M.D.

PMID- 15850895
TI  - Antioxidative properties of black tea.
AB  - BACKGROUND: Black tea, obtained by tea leaves fermentation, is an oxidized
      product and contains mainly multimeric polyphenols, whose biological activity is
      not well documented. This paper reviews the available literature on the effects
      of black tea on health with a focus on its antioxidative activity. METHODS: A
      review of the different issues and studies relating to composition,
      manufacturing, and antioxidative effects of black tea and its components in vitro
      as well as in vivo is presented. RESULTS: It is generally believed that
      polyphenols such as theaflavins and thearubigins as well as catechins as major
      constituents of black tea are mainly responsible for antioxidant actions.
      Antioxidative properties of black tea are manifested by its ability to inhibit
      free radical generation, scavenge free radicals, and chelate transition metal
      ions. Black tea, as well as individual theaflavins, can influence activation of
      transcription factors such as NFkappaB or AP-1. Theaflavins have been also proved
      to inhibit the activity of prooxidative enzymes such as xanthine oxidase or
      nitric oxide synthase. CONCLUSIONS: Black tea consumed throughout the world is
      believed to be not only a popular beverage but also an antioxidative agent
      available in everyday life.

PMID- 15850897
TI  - Evidence-based review of three-dimensional conformal radiotherapy for localized
      prostate cancer: an ASTRO outcomes initiative.
AB  - PURPOSE: To perform a systematic review of the evidence to determine the efficacy
      and effectiveness of three-dimensional conformal radiotherapy (3D-CRT) for
      localized prostate cancer; provide a clear presentation of the key clinical
      outcome questions related to the use of 3D-CRT in the treatment of localized
      prostate cancer that may be answered by a formal literature review; and provide
      concise information on whether 3D-CRT improves the clinical outcomes in the
      treatment of localized prostate cancer compared with conventional RT. METHODS AND
      MATERIALS: We performed a systematic review of the literature through a
      structured process developed by the American Society for Therapeutic Radiology
      and Oncology's Outcomes Committee that involved the creation of a
      multidisciplinary task force, development of clinical outcome questions, a formal
      literature review and data abstraction, data review, and outside peer review.
      RESULTS: Seven key clinical questions were identified. The results and task force
      conclusions of the literature review for each question are reported. CONCLUSION:
      The technological goals of reducing morbidity with 3D-CRT have been achieved.
      Randomized trials and follow-up of completed trials remain necessary to address
      these clinical outcomes specifically with regard to patient subsets and the use
      of hormonal therapy.

PMID- 15850898
TI  - Longitudinal multivoxel MR spectroscopy study of pediatric diffuse brainstem
      gliomas treated with radiotherapy.
AB  - BACKGROUND AND PURPOSE: After radiotherapy (RT), children with diffuse intrinsic
      pontine gliomas (DIPG) are followed with sequential magnetic resonance imaging
      (MRI). However, MRI changes do not necessarily reflect tumor progression, and
      therefore additional noninvasive tools are needed to improve the definition of
      progression vs. treatment-related changes. In this study, we determined the
      feasibility and accuracy of multivoxel proton magnetic resonance spectroscopic
      imaging (1H-MRSI) for monitoring pediatric patients with DIPG. METHODS AND
      PATIENTS: Twenty-four serial examinations of MRI/MRSI (7 2D-MRSI and 17 3D-MRSI)
      were performed on 8 patients with DIPG who received local RT. A total of 1635
      voxels were categorized as "normal" or "abnormal" based on corresponding imaging
      findings on contrast-enhanced T1- and T2-weighted MRI. The choline to N-acetyl
      aspartate ratio (Cho:NAA) and choline to creatine ratios (Cho:Cr) within each
      category of MRI abnormality were compared to their counterpart in normal
      surrounding tissues. The changes in these ratios corresponding to each type of
      abnormality were evaluated before RT, at response, and at recurrence, as
      determined by the clinical status of the patients. The presence or absence of
      lactate and lipid peaks was noted for each voxel. MRI/MRSI was performed on
      posterior fossa and supratentorial tissue of 3 volunteer pediatric patients.
      RESULTS: The Cho:NAA and Cho:Cr values within the imaging abnormalities (3.8 +/-
      0.93 and 3.55 +/- 1.37, respectively) were significantly higher than the mean
      values in normal-appearing regions (0.93 +/- 0.2 and 1.13 +/- 0.38, respectively)
      (p < 0.005). Cho:NAA values decreased from studies at diagnosis to the time of
      response to RT (3.12 +/- 0.5 and 2.08 +/- 0.73, respectively), followed by an
      increase at the time of relapse (from 1.83 +/- 0.92 to 4.29 +/- 1.08). Loss of
      lactate and lipid peaks correlated with response, and their presence and
      stability with relapse. In 3 patients, increased spectral abnormalities preceded
      the radiological and clinical deterioration by 2-5 months. CONCLUSION: Multivoxel
      MRSI is a feasible and reproducible noninvasive tool for assessing pediatric
      DIPG. Longitudinal multivoxel MRSI measurements have potential value in assessing
      response to radiation or other therapies, because they offer more coverage than
      single-voxel techniques and provide reliable spectral data.

PMID- 15850899
TI  - Gamma knife radiosurgery of radiation-induced intracranial tumors: local control,
      outcomes, and complications.
AB  - PURPOSE: To determine local control (LC) and complication rates for patients who
      underwent radiosurgery for radiation-induced intracranial tumors. METHODS AND
      MATERIALS: Review of a prospectively maintained database (2,714 patients)
      identified 16 patients (20 tumors) with radiation-induced tumors treated with
      radiosurgery between 1990 and 2004. Tumor types included typical meningioma
      (n=17), atypical meningioma (n=2), and schwannoma (n=1). Median patient age at
      radiosurgery was 47.5 years (range, 27-70 years). The median tumor margin dose
      was 16 Gy (range, 12-20 Gy). Median follow-up was 40.2 months (range, 10.8-146.2
      months). Time-to-event outcomes were calculated with Kaplan-Meier estimates.
      RESULTS: Three-year and 5-year LC rates were 100%. Three-year and 5-year overall
      survival rates were 92% and 80%, respectively. Cause-specific survival rates at 3
      and 5 years were 100%. Three patients died: 1 had in-field progression 65.1
      months after radiosurgery and later died of the tumor, 1 died of progression of a
      preexisting brain malignancy, and 1 died of an unrelated cause. One patient had
      increased seizure activity that correlated with development of edema seen on
      neuroimaging. CONCLUSIONS: LC, survival, and complication rates in our series are
      comparable to those in previous reports of radiosurgery for intracranial
      meningiomas. Also, LC rates with radiosurgery are at least comparable to those of
      surgical series for radiation-induced meningiomas. Radiosurgery is a safe and
      effective treatment option for radiation-induced intracranial tumors, most of
      which are typical meningiomas.

PMID- 15850900
TI  - Where to locate the isocenter? The treatment strategy for repeat trigeminal
      neuralgia radiosurgery.
AB  - PURPOSE: The purpose of this study is to investigate how the spatial relationship
      between the isocenters of the first and second radiosurgeries affects the overall
      outcome. METHODS AND MATERIALS: We performed a retrospective study on 40 patients
      who had repeat gamma knife radiosurgery for trigeminal neuralgia. Only one 4-mm
      isocenter was applied in both first and second radiosurgeries, with a maximum
      radiation dose of 75 Gy and 40 Gy, respectively. The MR scan of the first
      radiosurgery was registered to that of the second radiosurgery by a landmark
      based registration algorithm. The spatial relationship between the isocenter of
      the first and the second radiosurgeries was thus determined. The investigating
      parameters were the distance between the isocenters of the two separate
      radiosurgeries and isocenter proximity to the brainstem. The outcome end points
      were pain relief and dysesthesias. The median follow-up for the repeat
      radiosurgery was 28 months (range, 6-51 months). RESULTS: Pain relief was
      complete in 11 patients, nearly complete (> or =90%) in 7 patients, partial (> or
      =50%) in 8 patients, and minimal (<50%) or none in another 14 patients. The mean
      distance between the two isocenters was 2.86 mm in the complete or nearly
      complete pain relief group vs. 1.93 mm in the others. Farther distance between
      isocenters was associated with a trend toward better pain relief (p = 0.057). The
      proximity of the second isocenter to the brainstem did not affect pain relief,
      and neither did placing the second isocenter proximal or distal to the brainstem
      compared with the first one. Three patients developed moderate dysesthesias
      (score of 4 on a 0-10 scale), and 2 other patients developed more significant
      dysesthesias (score of 7) after the second radiosurgery. Dysesthesias related
      neither to distance between isocenters nor to which isocenter was closer to the
      brainstem. CONCLUSIONS: Image registration between MR scans of the first and
      second radiosurgeries helps target delineation and radiosurgery treatment
      planning. Increasing the isocenter distance between the two radiosurgeries
      treated a longer segment of the trigeminal neuralgia nerve and was associated
      with a trend toward improved pain relief.

PMID- 15850901
TI  - Stereotactic proton beam therapy for intracranial arteriovenous malformations.
AB  - PURPOSE: To investigate hypofractionated stereotactic proton therapy of
      predominantly large intracranial arteriovenous malformations (AVMs) by analyzing
      retrospectively the results from a cohort of patients. METHODS AND MATERIALS:
      Since 1993, a total of 85 patients with vascular lesions have been treated. Of
      those, 64 patients fulfilled the criteria of having an arteriovenous malformation
      and sufficient follow-up. The AVMs were grouped by volume: <14 cc (26 patients)
      and > or =14 cc (38 patients). Treatment was delivered with a fixed horizontal
      200 MeV proton beam under stereotactic conditions, using a stereophotogrammetric
      positioning system. The majority of patients were hypofractionated (2 or 3
      fractions), and the proton doses are presented as single-fraction equivalent
      cobalt Gray equivalent doses (SFEcGyE). The overall mean minimum target volume
      dose was 17.37 SFEcGyE, ranging from 10.38-22.05 SFEcGyE. RESULTS: Analysis by
      volume group showed obliteration in 67% for volumes <14 cc and 43% for volumes >
      or =14 cc. Grade IV acute complications were observed in 3% of patients.
      Transient delayed effects were seen in 15 patients (23%), becoming permanent in 3
      patients. One patient also developed a cyst 8 years after therapy. CONCLUSIONS:
      Stereotactic proton beam therapy applied in a hypofractionated schedule allows
      for the safe treatment of large AVMs, with acceptable results. It is an
      alternative to other treatment strategies for large AVMs. AVMs are likely not
      static entities, but probably undergo vascular remodeling. Factors influencing
      angiogenesis could play a new role in a form of adjuvant therapy to improve on
      the radiosurgical results.

PMID- 15850902
TI  - Multifractionated image-guided and stereotactic intensity-modulated radiotherapy
      of paraspinal tumors: a preliminary report.
AB  - PURPOSE: The use of image-guided and stereotactic intensity-modulated
      radiotherapy (IMRT) techniques have made the delivery of high-dose radiation to
      lesions within close proximity to the spinal cord feasible. This report presents
      clinical and physical data regarding the use of IMRT coupled with noninvasive
      body frames (stereotactic and image-guided) for multifractionated radiotherapy.
      METHODS AND MATERIALS: The Memorial Sloan-Kettering Cancer Center (Memorial)
      stereotactic body frame (MSBF) and Memorial body cradle (MBC) have been developed
      as noninvasive immobilizing devices for paraspinal IMRT using stereotactic (MSBF)
      and image-guided (MBC) techniques. Patients were either previously irradiated or
      prescribed doses beyond spinal cord tolerance (54 Gy in standard fractionation)
      and had unresectable gross disease involving the spinal canal. The planning
      target volume (PTV) was the gross tumor volume with a 1 cm margin. The PTV was
      not allowed to include the spinal cord contour. All treatment planning was
      performed using software developed within the institution. Isocenter verification
      was performed with an in-room computed tomography scan (MSBF) or electronic
      portal imaging devices, or both. Patients were followed up with serial magnetic
      resonance imaging every 3-4 months, and no patients were lost to follow-up.
      Kaplan-Meier statistics were used for analysis of clinical data. RESULTS: Both
      the MSBF and MBC were able to provide setup accuracy within 2 mm. With a median
      follow-up of 11 months, 35 patients (14 primary and 21 secondary malignancies)
      underwent treatment. The median dose previously received was 3000 cGy in 10
      fractions. The median dose prescribed for these patients was 2000 cGy/5 fractions
      (2000-3000 cGy), which provided a median PTV V100 of 88%. In previously
      unirradiated patients, the median prescribed dose was 7000 cGy (5940-7000 cGy)
      with a median PTV V100 of 90%. The median Dmax to the cord was 34% and 68% for
      previously irradiated and never irradiated patients, respectively. More than 90%
      of patients experienced palliation from pain, weakness, or paresthesia; 75% and
      81% of secondary and primary lesions, respectively, exhibited local control at
      the time of last follow-up. No cases of radiation-induced myelopathy or
      radiculopathy have thus far been encountered. CONCLUSIONS: Precision stereotactic
      and image-guided paraspinal IMRT allows the delivery of high doses of radiation
      in multiple fractions to tumors within close proximity to the spinal cord while
      respecting cord tolerance. Although preliminary, the clinical results are
      encouraging.

PMID- 15850903
TI  - Why to start the concomitant boost in accelerated radiotherapy for advanced
      laryngeal cancer in week 3.
AB  - PURPOSE: We analyzed toxicity and the local control rates for advanced laryngeal
      cancer, treated with two accelerated fractionation schedules. The main difference
      between the schedules was the onset of the concomitant boost, in Week 3 or Week
      4. Overall treatment time and total dose were equivalent. METHODS AND MATERIALS:
      In a prospective, nonrandomized study of T3, T4, and advanced T2 laryngeal
      cancer, concomitant boost schedules were used in 100 patients. Thirty patients
      received a schedule of twice daily 1.2 Gy in Weeks 1-3, followed by twice daily
      1.7 Gy in Weeks 4 and 5; total dose was 70 Gy (the hyperfractionated accelerated
      schedule [HAS] regimen). Seventy patients were treated with 5 times 2 Gy in Weeks
      1 and 2, followed by daily 1.8 Gy and 1.5 Gy (boost) in Weeks 3-5; total dose
      69.5 Gy (the accelerated schedule only [ASO] regimen). Distribution of T stage
      was 47%, 40%, and 12% for T2, T3, and T4, respectively. In 24% of the patients,
      lymph nodes were positive. Pretreatment tracheotomy or stridor or both occurred
      in 8 patients. The distribution of prognostic factors was not significantly
      different between the two fractionation schedules. Acute and late toxicity was
      assessed. Results were estimated by the use of actuarial methods. For late
      toxicity and local control univariate and multivariate analyses were performed.
      Tumor control probability analysis was used to model cure rate differences.
      RESULTS: Overall acute mucositis score was equal for both schedules. Acute
      mucositis started and decreased significantly earlier in the HAS regimen. In all
      patients acute mucositis healed completely. The treatment was completed within 38
      days in all patients. The regional control rate was 100% for clinical N0, and 75%
      for the clinical N+ patients. The 3-year local control rate was 59% and 78% for
      the HAS and ASO regimens, respectively (p = 0.05); the ultimate local control was
      80% and 94%, respectively. In multivariate analysis, besides the fractionation
      schedule (relative risk [RR], 2.6 for HAS vs. ASO), pretreatment
      tracheotomy/stridor (RR 4.3, yes vs. no), and local tumor response 3-6 weeks
      after radiotherapy (RR 5.1, no vs. yes) were independent factors for local
      control. Tumor control probability analysis indicated that the onset of
      repopulation may be about 4-6 days earlier for the HAS regimen. The onset of
      repopulation in the HAS regimen is probably at the end of the second week or at
      the beginning of the third week. Severe late toxicity was observed in the HAS
      group and ASO group in, respectively, 11% and 16%. In multivariate analysis this
      toxicity related significantly to the field size and pretreatment
      tracheotomy/stridor. CONCLUSIONS: In our study the timing of the boost in
      accelerated radiotherapy for advanced laryngeal cancer was an independent factor
      for local control, favoring the use of a concomitant boost in Week 3. This
      finding may indicate that accelerated repopulation of tumor cells starts early in
      the treatment phase.

PMID- 15850904
TI  - Does registration of PET and planning CT images decrease interobserver and
      intraobserver variation in delineating tumor volumes for non-small-cell lung
      cancer?
AB  - PURPOSE: To compare tumor volume delineation using registered positron emission
      tomography (PET)/CT vs. side-by-side image sets. METHODS AND MATERIALS: A total
      of 19 patients with non-small-cell lung cancer had 18-fluorine-deoxyglucose (FDG)
      PET scans registered with planning CT scans. The disease was Stage I-II in 26%,
      IIIA in 42%, and IIIB in 32%. Two radiation oncologists contoured 9 tumor volumes
      using registered images (registered) and 10 using separate FDG-PET images as a
      guide (nonregistered). A third physician, who had done the treatment planning for
      these patients a median of 40 months before using registered images, repeated all
      contours: 10 on registered images (registered/registered) and 9 without
      registration (registered/nonregistered). Each pair of volumes (A and B) was
      compared. Quantitative comparison used the concordance index, (A intersection
      B)/(A union or logical sum B). For qualitative analysis, pairs of volumes were
      projected onto digitally reconstructed radiographs. The differences were graded
      as insignificant, minor, moderate, or major. RESULTS: The median interobserver
      percentage of concordance among nonregistered pairs was 61% vs. 70% in the
      registered group (p <0.05). On qualitative analysis, in the nonregistered group,
      the differences were insignificant in 5, minor in 3, and moderate in 2 of 10. The
      differences in the registered group were insignificant in 7 and minor in 2 of 9.
      The median intraobserver percentage of concordance in the
      registered/nonregistered group was 58% vs. 71% in the registered/registered group
      (p = 0.10). On qualitative analysis, the intraobserver differences in the
      registered/nonregistered group were insignificant in 2, minor in 2, moderate in
      0, and major in 5 of 9. In the registered/registered group, the differences were
      insignificant in 2, minor in 6, moderate in 2, and major in 0 of 10. CONCLUSION:
      Registration of FDG-PET and planning CT images results in greater consistency in
      tumor volume delineation.

PMID- 15850905
TI  - Phase II study of radiotherapy with three-dimensional conformal boost concurrent
      with paclitaxel and cisplatin for Stage IIIB non-small-cell lung cancer.
AB  - PURPOSE: To evaluate the efficacy and toxicity of concurrent chemoradiotherapy
      with paclitaxel/cisplatin for Stage IIIB locally advanced non-small-cell lung
      cancer (NSCLC). METHODS AND MATERIALS: Radiotherapy was administered to a total
      dose of 70.2 Gy (daily fraction of 1.8 Gy, 5 days/wk), over an 8-week period,
      combined with chemotherapy. The chemotherapy consisted of weekly 40 mg/m2 of
      paclitaxel plus 20 mg/m2 of cisplatin for 8 consecutive weeks. All patients
      received three-dimensional conformal radiotherapy (3D-CRT), based on computed
      tomography simulated planning after 41.4 Gy. The median follow-up period of
      survivors was 24 months. RESULTS: Between January 2000 and October 2002, 135
      patients with a median age of 60 years were enrolled and analyzed in this
      prospective trial. The overall response rate was 75% including 2 cases of
      complete response. The major patterns of failure were local failure and distant
      metastasis. The 2-year overall and progression-free survival rates were 37% and
      18%, respectively. The median overall and progression-free survival times were 17
      months and 9 months, respectively. Hematologic toxicity >Grade 2 was observed in
      19% of patients and severe non-hematologic toxicity was infrequent. CONCLUSIONS:
      Three-dimensional conformal radiotherapy, combined with paclitaxel and cisplatin
      chemotherapy, was associated with a satisfactory outcome with manageable
      toxicity. Further investigations are needed to improve the local control.

PMID- 15850906
TI  - Influence of number of metastatic lymph nodes on survival of curative resected
      thoracic esophageal cancer patients and value of radiotherapy: report of 549
      cases.
AB  - PURPOSE: To analyze the significance of the number of metastatic lymph nodes on
      survival with and without the addition of prophylactic postoperative radiotherapy
      (RT) after radical resection of thoracic esophageal carcinoma. METHODS AND
      MATERIALS: A total of 549 thoracic esophageal squamous cell cancer patients who
      had undergone radical resection were randomized by the envelope method into a
      surgery-alone group (S, n = 275) and a surgery plus RT group (S+R, n = 274). We
      performed a retrospective review of all patients according to the extent of
      metastasis. The patients were classified into three groups: Group 1, 269 patients
      (49.0%) without lymph node involvement; Group 2, 159 patients (29.0%) with one to
      two positive nodes; and Group 3, 121 patients (22.0%) with three or more positive
      lymph nodes. RESULTS: For the same T stage (T3), the 5-year survival rate for
      Groups 1, 2, and 3 was 50.6%, 29.3%, and 11.7%, respectively (p = 0.0000). For
      patients with Stage III, the 5-year survival rate for Groups 1 (T4N0M0), 2 (T3
      T4N1M0), and 3 (T3-T4N2M0) was 58.1%, 30.6%, and 14.4%, respectively (p =
      0.0092). The 5-year survival rate of the S and S+R groups with positive lymph
      nodes (Groups 2 and 3) was 17.6% and 34.1% (p = 0.0378). In the positive lymph
      node groups, the incidence of failure by intrathoracic lymph node metastasis and
      supraclavicular lymph node metastasis in the S+R group (21.5% and 4.6%,
      respectively) was lower than in the S group (35.9% and 19.7%, respectively; p
      <0.012). In the negative lymph node group, the incidence of failure by
      intrathoracic lymph node metastasis in the S and S+R groups was 27.8% and 13.3%,
      respectively (p = 0.006). Hematogenous metastasis was the greatest (27.5%) in
      Group 3 (three or more positive lymph nodes). CONCLUSION: The number of
      metastatic lymph nodes is one of the important factors affecting the survival of
      patients with thoracic esophageal carcinoma. In our study, postoperative RT
      improved the survival of patients with positive lymph nodes. Additionally,
      postoperative RT reduced the incidence of intrathoracic recurrence and
      supraclavicular lymph node metastasis for all patients.

PMID- 15850907
TI  - Phase I trial of oxaliplatin in combination with cisplatin, protacted-infusion
      fluorouracil, and radiotherapy in advanced esophageal and gastroesophageal
      carcinoma.
AB  - PURPOSE: To define the maximum-tolerated dose of oxaliplatin given with
      cisplatin, protacted 96-h infusion of fluorouracil, and radiotherapy for patients
      with advanced esophageal cancer. PATIENTS AND METHODS: Seventeen patients with
      locally advanced esophageal cancer and 2 patients with local recurrence were
      treated. Escalating doses of oxaliplatin, cisplatin, and fluorouracil were
      administered on Days 1 and 29 of radiotherapy. Radiotherapy was delivered in 1.8
      Gy daily fractions to a total dose of 50.4 Gy. Dose-limiting toxicity was defined
      as a Grade 4 hematologic or Grade 3-4 nonhematologic toxicity. RESULTS: Dose
      limiting toxicity caused by diarrhea and asthenia was observed at the IV level.
      The recommended dose was 85 mg/m- oxaliplatin, 55 mg/m2 cisplatin, and 3000 mg/m2
      96-h fluorouracil infusion. Two pathologic complete responses were observed in 12
      patients selected for surgery (16%). CONCLUSIONS: Oxaliplatin, cisplatin,
      fluouracil, and radiotherapy can be administered together with acceptable
      toxicity. A Phase II trial is ongoing with resectable esophageal and gastric
      carcinoma.

PMID- 15850908
TI  - Clinical experience with chronomodulated infusional 5-fluorouracil
      chemoradiotherapy for pancreatic adenocarcinoma.
AB  - PURPOSE: To evaluate retrospectively the efficacy and chronic toxicities of
      concurrent radiotherapy and chronomodulated infusion 5-fluorouracil (5-FU) in
      patients with pancreatic adenocarcinoma. METHODS AND MATERIALS: Twenty-eight
      patients with pancreatic adenocarcinoma were treated between January 1997 and May
      2000 with 5-FU chronomodulated chemoradiotherapy. Chronomodulated delivery of
      chemotherapy was chosen on the basis of a lower toxicity profile in the treatment
      of GI malignancies. The median age was 64 years. Of the 28 patients, 12 were men
      and 16 were women. Eight patients had unresectable disease and 20 were treated
      after pancreatic resection. The median radiation dose was 50.4 Gy given in 28
      fractions. The median field length and width was 10.6 cm and 10.9 cm,
      respectively. Concurrent chemotherapy with 5-FU was administered 5 d/wk, with a
      median total dose of 8.4 g/m2 (300 mg/m2/d). Chronomodulated 5-FU delivery
      consisted of a low basal infusion for 16 h followed by an 8-h escalating
      deescalating infusion peaking at 10 pm. Survival and recurrence data were
      evaluated using Kaplan-Meier actuarial analysis. Toxicities were recorded using
      the Radiation Therapy Oncology Group grading system. RESULTS: The median follow
      up for all patients was 26 months (range, 4-68 months). The median overall
      survival for the 20 patients treated postoperatively was 34 months, with a 3- and
      5-year actuarial survival rate of 40% and 21%, respectively. If the 3 patients
      with carcinoma of the ampulla were removed from the data set, the mean overall
      survival in the resected patients was 34 months, with a 3-year and 5-year
      actuarial survival rate of 40% and 17%, respectively. The 8 unresectable patients
      had a median overall survival of 14 months, and none lived past 2 years. No
      patient experienced Grade 3 or 4 hematologic toxicity or weight loss. Five
      patients had nausea and dehydration requiring i.v. fluids; only one (4%) was
      hospitalized. Four patients required a dose reduction of 5-FU, one for nausea,
      one for a transient ischemic attack, one for an infection, and one because of
      myocardial infarction. Seven resected patients, four of whom had no evidence of
      disease, developed diabetes mellitus 1-2 years after radiotherapy. CONCLUSION:
      Chronomodulated 5-FU administration, based on the concept of chronotolerance, has
      relatively low acute toxicity. Our median survival rate was greater than that
      after most chemoradiotherapy programs that result in more acute toxicity.
      Additional study is warranted to evaluate chronomodulated radiosensitizing
      chemotherapy schedules in prospective trials and with attention to late effects
      after radiotherapy, including diabetes mellitus.

PMID- 15850909
TI  - Consolidative abdominopelvic radiotherapy after surgery and
      carboplatin/paclitaxel chemotherapy for epithelial ovarian cancer.
AB  - PURPOSE: To assess the feasibility and morbidity of sequential cytoreductive
      surgery, carboplatin/paclitaxel chemotherapy, and consolidative abdominopelvic
      radiotherapy (APRT) in ovarian cancer. METHODS AND MATERIALS: Between 1998 and
      2000, 29 patients with optimally cytoreduced epithelial ovarian cancer were
      treated with carboplatin (135 mg/m2) and paclitaxel (area under the curve [AUC]
      of 6) followed by APRT in a prospective protocol. All patients were clinically,
      radiographically, and biochemically (CA-125) free of disease at the completion of
      chemotherapy. Abdominopelvic radiotherapy was delivered using 6 MV anterior
      posterior photon fields to encompass the peritoneal cavity. Median follow-up was
      4 years. RESULTS: Two patients experienced Radiation Therapy Oncology Group Grade
      3 gastrointestinal toxicity during APRT; 6 patients, Grade 3 or 4 neutropenia;
      and 3 patients, Grade 3 or 4 thrombocytopenia. Overall, 10 patients had Grade 3
      or 4 acute toxicity. All of the acute side effects resolved after treatment was
      completed, and there were no serious consequences such as sepsis or hemorrhage.
      Abdominopelvic radiotherapy was abandoned prematurely in 3 patients. Late side
      effects were seen in 5 patients, including 1 small bowel obstruction, 2
      symptomatic sacral insufficiency fractures, 1 case of severe dyspareunia, and 1
      case of prolonged fatigue. All resolved with supportive management. The 4-year
      actuarial disease-free survival was 57%, and the overall survival was 92%. Eleven
      of 12 patients who relapsed received salvage chemotherapy, which was well
      tolerated. CONCLUSIONS: Abdominopelvic radiotherapy after optimal surgery and
      carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of
      acute and late side effects and does not limit subsequent salvage chemotherapy.
      Consolidative APRT warrants further investigation as a means of improving the
      outcome of patients with ovarian cancer.

PMID- 15850910
TI  - Intravaginal brachytherapy alone for intermediate-risk endometrial cancer.
AB  - PURPOSE: Despite the results of the Gynecologic Oncology Group trial No. 99
      (GOG#99), some unanswered questions still remain about the role of adjuvant
      radiotherapy (RT) for intermediate-risk endometrial cancer. First, can
      intravaginal brachytherapy (IVRT) alone substitute for external beam RT but
      without added morbidity? Second, is the high-risk (HR) definition from GOG#99 a
      useful tool to predict pelvic recurrence specifically? The purpose of this study
      was to try to answer these questions in a group of patients with Stage IB-IIB
      endometrial carcinoma treated with high-dose-rate (HDR) IVRT alone. METHODS AND
      MATERIALS: Between November 1987 and December 2002, 382 patients with Stage IB
      IIB endometrial carcinoma were treated with simple hysterectomy followed by HDR
      IVRT alone at our institution. Comprehensive surgical staging (CSS), defined as
      pelvic washings and pelvic/paraaortic lymph node sampling, was performed in 20%
      of patients. The mean age was 60 years (range, 29-92 years). Lymphovascular
      invasion (LVI) was present in 14% of patients. The median HDR-IVRT dose was 21 Gy
      (range, 6-21 Gy), given in three fractions. Complications were assessed in terms
      of late Radiation Therapy Oncology Group (Grade 3 or worse) toxicity of the GI
      tract, genitourinary GU tract, and vagina. RESULTS: With a median follow-up of 48
      months, the 5-year vaginal/pelvic control rate was 95% (95% confidence interval
      [CI], 93-98%). On multivariate analysis, a poor vaginal/pelvic control rate
      correlated with age > or =60 years old (relative risk [RR], 3, 95% CI, 1-12; p =
      0.01), International Federation of Gynecology and Obstetrics (FIGO) Grade 3 (RR,
      9, 95% CI, 2-35; p = 0.03), and LVI (RR, 4, 95% CI, 1-13; p = 0.051). The depth
      of myometrial invasion and CSS, however, were not significant. With regard to
      pelvic control specifically, the presence of GOG#99 HR features did not affect
      the pelvic control rate. The 5-year rate for HR patients was 96% (95% CI, 90
      100%) vs. 96% (95% CI, 94-99%) for those without HR disease (p = 0.48). Even when
      the CSS effect was taken into account, the influence of HR features on pelvic
      control was still not significant (p = 0.51). In contrast, pelvic control was
      significantly influenced when patients were grouped according to CSS and
      stage/grade substages. For those with Stage IB Grade 3-IIB and no CSS, the 5-year
      pelvic control rate was 86% compared with 97% for those with Stage IB Grade 3-IIB
      and CSS, 97% for Stage IB, Grade 1-2 without CSS, and 100% for those with Stage
      IB, Grade 1-2 and CSS (p = 0.027). The 5-year disease-free survival rate was 93%
      (95% CI, 90-96%). On multivariate analysis, poor disease-free survival correlated
      with age > or =60 years (RR, 5; 95% CI, 1-18; p = 0.002), FIGO Grade 3 (RR 5, 95%
      CI 2-17; p = 0.013), and LVI (RR 3, 95% CI 1-8; p = 0.054). Unlike pelvic
      control, disease-free survival was significantly affected by GOG#99 HR features,
      with a 5-year rate of 87% (95% CI, 76-99%) vs. 94% (95% CI, 91-97%) for those
      without HR features (p = 0.027). The 5-year overall and disease-specific survival
      rate was 93% and 97%, respectively. The overall 5-year actuarial rate of Grade 3
      or worse complications was 1% (95% CI, 0-2%). CONCLUSION: Tumor grade, depth of
      invasion, and the use of CSS were better predictors of pelvic control than the
      GOG#99 HR factors. IVRT alone seemed to provide adequate tumor control with very
      low morbidity. Therefore, it seems prudent to consider it for intermediate-risk
      patients because of its superior therapeutic ratio compared with that for surgery
      alone or pelvic RT. Additional follow-up, however, with a larger number of
      patients is needed, especially for those with LVI.

PMID- 15850911
TI  - Fractionated stereotactic radiotherapy boost for gynecologic tumors: an
      alternative to brachytherapy?
AB  - PURPOSE: A brachytherapy (BT) boost to the vaginal vault is considered standard
      treatment for many endometrial or cervical cancers. We aimed to challenge this
      treatment standard by using stereotactic radiotherapy (SRT) with a linac-based
      micromultileaf collimator technique. METHODS AND MATERIALS: Since January 2002,
      16 patients with either endometrial (9) or cervical (7) cancer have been treated
      with a final boost to the areas at higher risk for relapse. In 14 patients, the
      target volume included the vaginal vault, the upper vagina, the parametria, or
      (if not operated) the uterus (clinical target volume [CTV]). In 2 patients with
      local relapse, the CTV was the tumor in the vaginal stump. Margins of 6-10 mm
      were added to the CTV to define the planning target volume (PTV).
      Hypofractionated dynamic-arc or intensity-modulated radiotherapy techniques were
      used. Postoperative treatment was delivered in 12 patients (2 x 7 Gy to the PTV
      with a 4-7-day interval between fractions). In the 4 nonoperated patients, a dose
      of 4 Gy/fraction in 5 fractions with 2 to 3 days' interval was delivered.
      Patients were immobilized in a customized vacuum body cast and optimally
      repositioned with an infrared-guided system developed for extracranial SRT. To
      further optimize daily repositioning and target immobilization, an inflated
      rectal balloon was used during each treatment fraction. In 10 patients, CT
      resimulation was performed before the last boost fraction to assess for
      repositioning reproducibility via CT-to-CT registration and to estimate PTV
      safety margins around the CTV. Finally, a comparative treatment planning study
      between BT and SRT was performed in 2 patients with an operated endometrial Stage
      I cancer. RESULTS: No patient developed severe acute urinary or low-intestinal
      toxicity. No patient developed urinary late effects (>6 months). One patient with
      a vaginal relapse previously irradiated to the pelvic region presented with Grade
      3 rectal bleeding 18 months after retreatment. A second patient known to suffer
      from irritable bowel syndrome presented with Grade 1 abdominal pain after
      treatment. The estimated PTV margins around the CTV were 9-10 mm with infrared
      marker registration. External SRT succeeded in improving dose homogeneity to the
      PTV and in reducing the maximum dose to the rectum, when compared to BT.
      CONCLUSION: These results suggest that the use of external SRT to deliver a final
      boost to the areas at higher risk for relapse in endometrial or cervical cancer
      is feasible, well tolerated, and may well be considered an acceptable alternative
      to BT.

PMID- 15850912
TI  - High-dose-rate brachytherapy in uterine cervical carcinoma.
AB  - PURPOSE: High-dose-rate (HDR) brachytherapy is in wide use for curative treatment
      of cervical cancer. The American Brachytherapy Society has recommended that the
      individual fraction size be <7.5 Gy and the range of fractions should be four to
      eight; however, many fractionation schedules, varying from institution to
      institution, are in use. We use 9 Gy/fraction of HDR in two to five fractions in
      patients with carcinoma of the uterine cervix. We found that our results and
      toxicity were comparable to those reported in the literature and hereby present
      our experience with this fractionation schedule. METHODS AND MATERIALS: A total
      of 121 patients with Stage I-III carcinoma of the uterine cervix were treated
      with HDR brachytherapy between 1996 and 2000. The total number of patients
      analyzed was 113. The median patient age was 53 years, and the histopathologic
      type was squamous cell carcinoma in 93% of patients. The patients were subdivided
      into Groups 1 and 2. In Group 1, 18 patients with Stage Ib-IIb disease, tumor
      size <4 cm, and preserved cervical anatomy underwent simultaneous external beam
      radiotherapy to the pelvis to a dose of 40 Gy in 20 fractions within 4 weeks with
      central shielding and HDR brachytherapy of 9 Gy/fraction, given weekly, and
      interdigitated with external beam radiotherapy. The 95 patients in Group 2, who
      had Stage IIb-IIIb disease underwent external beam radiotherapy to the pelvis to
      a dose of 46 Gy in 23 fractions within 4.5 weeks followed by two sessions of HDR
      intracavitary brachytherapy of 9 Gy each given 1 week apart. The follow-up range
      was 3-7 years (median, 36.4 months). Late toxicity was graded according to the
      Radiation Therapy Oncology Group criteria. RESULTS: The 5-year actuarial local
      control and disease-free survival rate was 74.5% and 62.0%, respectively. The
      actuarial local control rate at 5 years was 100% for Stage I, 80% for Stage II,
      and 67.2% for Stage III patients. The 5-year actuarial disease-free survival rate
      was 88.8% for Stage I, 76.52% for Stage II, and 50.4% for Stage III patients.
      Local failure occurred in 2 (11.1%) of the 18 Group 1 patients and in 20 (21.0%)
      of the 95 Group 2 patients. Distant failure occurred in none of the Group 1
      patients and in 8 (8.4%) of the 95 Group 2 patients. None of the patients
      developed Grade 3 rectal toxicity. Grade 3 bladder toxicity was observed in 2
      patients. The actuarial risk of Grade 3 or worse late toxicity was 3.31%.
      CONCLUSION: The results of our study indicate that HDR brachytherapy at 9
      Gy/fraction is both safe and effective in the management of carcinoma of the
      cervix, with good local control and a minimum of normal tissue toxicity.

PMID- 15850913
TI  - Comparison between CT-based volumetric calculations and ICRU reference-point
      estimates of radiation doses delivered to bladder and rectum during intracavitary
      radiotherapy for cervical cancer.
AB  - PURPOSE: To compare CT-based volumetric calculations and International Commission
      on Radiation Units and Measurements (ICRU) reference-point estimates of radiation
      doses to the bladder and rectum in patients with carcinoma of the uterine cervix
      treated with definitive low-dose-rate intracavitary radiotherapy (ICRT). METHODS
      AND MATERIALS: Between November 2001 and March 2003, 60 patients were
      prospectively enrolled in a pilot study of ICRT with CT-based dosimetry. Most
      patients underwent two ICRT insertions. After insertion of an afterloading ICRT
      applicator, intraoperative orthogonal films were obtained to ensure proper
      positioning of the system and to facilitate subsequent planning. Treatments were
      prescribed using standard two-dimensional dosimetry and planning. Patients also
      underwent helical CT of the pelvis for three-dimensional reconstruction of the
      radiation dose distributions. The systems were loaded with 137Cs sources using
      the Selectron remote afterloading system according to institutional practice for
      low-dose-rate brachytherapy. Three-dimensional dose distributions were generated
      using the Varian BrachyVision treatment planning system. The rectum was contoured
      from the bottom of the ischial tuberosities to the sigmoid flexure. The entire
      bladder was contoured. The minimal doses delivered to the 2 cm3 of bladder and
      rectum receiving the highest dose (DBV2 and DRV2, respectively) were determined
      from dose-volume histograms, and these estimates were compared with two
      dimensionally derived estimates of the doses to the corresponding ICRU reference
      points. RESULTS: A total of 118 unique intracavitary insertions were performed,
      and 93 were evaluated and the subject of this analysis. For the rectum, the
      estimated doses to the ICRU reference point did not differ significantly from the
      DRV2 (p = 0.561); the mean (+/- standard deviation) difference was 21 cGy (+/-
      344 cGy). The median volume of the rectum that received at least the ICRU
      reference-point dose was 2.1 cm3. In 66 (71%) of 93 cases, <5 cm3 was treated to
      this dose. However, for the bladder, the estimated doses to the ICRU reference
      point were significantly lower than the D(BV2) (p <0.001); the mean difference
      was 680 cGy (+/- 543 cGy). The median volume of the bladder that received at
      least the ICRU reference-point dose was 13.0 cm3. CONCLUSIONS: Our data suggest
      that the estimated dose to the ICRU rectal point may be a reasonable surrogate
      for the DRV2. However, this result may not be applicable to other treatment
      guidelines and ICRT applicator systems. In contrast, the dose to the ICRU bladder
      point does not appear to be a reasonable surrogate for the DBV2. Correlation with
      late complications are needed to define the role of three-dimensional dosimetry
      in treatment planning.

PMID- 15850914
TI  - Definitive radiation therapy for squamous cell carcinoma of the vagina.
AB  - PURPOSE: To evaluate outcome and describe clinical treatment guidelines for
      patients with primary squamous cell carcinoma of the vagina treated with
      definitive radiation therapy. METHODS AND MATERIALS: Between 1970 and 2000, a
      total of 193 patients were treated with definitive radiation therapy for squamous
      cell carcinoma of the vagina at The University of Texas M. D. Anderson Cancer
      Center. The patients' medical records were reviewed to obtain information about
      patient, tumor, and treatment characteristics, as well as outcome and patterns of
      recurrence. Surviving patients were followed for a median of 137 months. Survival
      rates were calculated using the Kaplan-Meier method, with differences assessed
      using log-rank tests. RESULTS: Disease-specific survival (DSS) and pelvic disease
      control rates correlated with International Federation of Gynecology and
      Obstetrics (FIGO) stage and tumor size. At 5 years, DSS rates were 85% for the 50
      patients with Stage I, 78% for the 97 patients with Stage II, and 58% for the 46
      patients with Stage III-IVA disease (p = 0.0013). Five-year DSS rates were 82%
      and 60% for patients with tumors < or =4 cm or >4 cm, respectively (p = 0.0001).
      At 5 years, pelvic disease control rates were 86% for Stage I, 84% for Stage II,
      and 71% for Stage III-IVA (p = 0.027). The predominant mode of relapse after
      definitive radiation therapy was local-regional (68% and 83%, respectively, for
      patients with stages I-II or III-IVA disease). The incidence of major
      complications was correlated with FIGO stage; at 5 years, the rates of major
      complications were 4% for Stage I, 9% for Stage II, and 21% for Stage III-IVA (p
      < 0.01). CONCLUSIONS: Excellent outcomes can be achieved with definitive
      radiation therapy for invasive squamous cell carcinoma of the vagina. However, to
      achieve these results, treatment must be individualized according to the site and
      size of the tumor at presentation and the response to initial external-beam
      radiation therapy. Brachytherapy plays an important role in the treatment of many
      vaginal cancers but should be carefully selected and applied to obtain optimal
      coverage of the target volume.

PMID- 15850915
TI  - PSA doubling time kinetics during prostate cancer biochemical relapse after
      external beam radiation therapy.
AB  - PURPOSE: To investigate whether prostate-specific antigen PSA doubling time
      (PSADT) is constant in men with biochemical prostate cancer relapse after
      external beam radiotherapy (EBRT). METHODS AND MATERIALS: A total of 513 men
      treated radically with EBRT, with or without androgen ablation (AA), between 1993
      and 2000, developed biochemical relapse. The slope of the ln (PSA) vs. time graph
      is calculated for the first two values after PSA nadir (first slope), the last
      two recorded PSAs (last slope), and all values excluding the first and final PSA
      (mid slope). Differences in these slopes were compared statistically with
      subgroup analysis for AA and secondary intervention. RESULTS: For men treated
      with EBRT and AA first slope was faster than either mid slope (p = 0.031) or last
      slope (p < 0.001). Men treated with EBRT alone had no change in PSADT over time
      unless they subsequently received secondary intervention. This group had a more
      rapid last slope compared with mid slope (p < 0.001). CONCLUSIONS: PSA initially
      rises more rapidly after AA cessation, probably because of testosterone recovery.
      A subgroup of patients, who received secondary intervention after treatment with
      radiotherapy alone, showed a change in PSADT, to a faster velocity. This greater
      than constant exponential PSA growth is presumably the catalyst for secondary
      intervention. Otherwise, PSADT did not change during prostate cancer biochemical
      relapse.

PMID- 15850916
TI  - An automatic CT-guided adaptive radiation therapy technique by online
      modification of multileaf collimator leaf positions for prostate cancer.
AB  - PURPOSE: To propose and evaluate online adaptive radiation therapy (ART) using in
      room computed tomography (CT) imaging that detects changes in the target position
      and shape of the prostate and seminal vesicles (SVs) and then automatically
      modifies the multileaf collimator (MLC) leaf pairs in a slice-by-slice fashion.
      METHODS AND MATERIALS: For intensity-modulated radiation therapy (IMRT) using a
      coplanar beam arrangement, each MLC leaf pair projects onto a specific anatomic
      slice. The proposed strategy assumes that shape deformation is a function of only
      the superior-inferior (SI) position. That is, there is no shape change within a
      CT slice, but each slice can be displaced in the anteroposterior (AP) or right
      left (RL) direction relative to adjacent slices. First, global shifts (in SI, AP,
      and RL directions) were calculated by three-dimensional (3D) registration of the
      bulk of the prostate in the treatment planning CT images with the daily CT images
      taken immediately before treatment. Local shifts in the AP direction were then
      found using slice-by-slice registration, in which the CT slices were individually
      registered. The translational shift within a slice could then be projected to a
      translational shift in the position of the corresponding MLC leaf pair for each
      treatment segment for each gantry angle. Global shifts in the SI direction were
      accounted for by moving the open portal superiorly or inferiorly by an integral
      number of leaf pairs. The proposed slice-by-slice registration technique was
      tested by using daily CT images from 46 CT image sets (23 each from 2 patients)
      taken before the standard delivery of IMRT for prostate cancer. A dosimetric
      evaluation was carried out by using an 8-field IMRT plan. RESULTS: The shifts and
      shape change of the prostate and SVs could be separated into 3D global shifts in
      the RL, AP, and SI directions, plus local shifts in the AP direction, which were
      different for each CT slice. The MLC leaf positions were successfully modified to
      compensate for these global shifts and local shape variations. The ART method
      improved geometric coverage of the prostate and SVs compared with the couch-shift
      method, particularly for the superior part of the prostate and all the SVs, for
      which the interfraction shape change was the largest. The dosimetric comparison
      showed that the ART method covered the target better and reduced the rectal dose
      more than a simple couch-translation method. CONCLUSIONS: ART corrected for
      interfraction changes in the position and shape of the prostate and SVs and gave
      dose distributions that were considerably closer to the planned dose
      distributions than could be achieved with simple alignment strategies that
      neglect shape change. The ART proposed in this investigation requires neither
      contouring of the daily CT images nor extensive calculations; therefore, it may
      prove to be an effective and clinically practical solution to the problem of
      interfraction shape changes.

PMID- 15850917
TI  - Prophylactic tamsulosin (Flomax) in patients undergoing prostate 125I
      brachytherapy for prostate carcinoma: final report of a double-blind placebo
      controlled randomized study.
AB  - PURPOSE: To evaluate the effectiveness of prophylactic tamsulosin (Flomax) in
      reducing the urinary symptoms in patients undergoing 125I prostate implantation
      (PI) for prostate adenocarcinoma. METHODS AND MATERIALS: This is a single
      institution, double-blind, placebo-controlled, randomized trial for patients
      undergoing PI for prostate adenocarcinoma comparing prophylactic tamsulosin
      versus placebo. Eligibility criteria included patients not taking tamsulosin or
      other alpha-blockers treated with PI. The patients were randomly assigned to
      either tamsulosin (0.8 mg, orally once a day) or matched placebo. All patients
      started the medication 4 days before PI and continued for 60 days. The American
      Urologic Association (AUA) symptom index questionnaire was used to assess urinary
      symptoms. The AUA questionnaire was administered before PI for a baseline score
      and weekly for 8 weeks after PI. Patients were taken off the study if they
      developed urinary retention, had intolerable urinary symptoms, or wished to
      discontinue with the trial. RESULTS: One hundred twenty-six patients were
      enrolled in this study from November 2001 to January 2003 (118 were evaluable: 58
      in the tamsulosin arm and 60 in the placebo group). Pretreatment and treatment
      characteristics were comparably matched between the two groups. The urinary
      retention rate was 17% (10 patients) in the placebo group compared with 10% (6
      patients) in the tamsulosin group (p = 0.3161). Eighty-eight percent (14
      patients) of those who developed urinary retention experienced it within 2 weeks
      after the PI. Intolerable urinary symptoms were reported equally (10 patients in
      each group) with 70% occurring in the first 2 weeks after PI. There was a
      significant difference in mean AUA score in favor of tamsulosin at Week 5 after
      PI (p = 0.03). CONCLUSIONS: Prophylactic tamsulosin (0.8 mg/day) before prostate
      brachytherapy did not significantly affect urinary retention rates, but had a
      positive effect on urinary morbidity at Week 5 after PI.

PMID- 15850918
TI  - High-dose regions versus likelihood of cure after prostate brachytherapy.
AB  - PURPOSE: To analyze the effect of high-dose regions on biochemical cancer control
      rates after prostate brachytherapy. METHODS AND MATERIALS: Patients with 1997
      American Joint Committee on Cancer clinical Stage T1c-T2a prostate carcinoma
      (Gleason grade 5-6, prostate-specific antigen level 4-10 ng/mL) were randomized
      to implantation with 125I (144 Gy) vs. 103Pd (125 Gy, National Institute of
      Standards and Technology 1999). Isotope implantation was performed by standard
      techniques, using a modified peripheral loading pattern. Of the 313 patients
      entered in the protocol, 270 were included in this analysis. The 125I source
      strength ranged from 0.4 to 0.89 mCi (median, 0.55 mCi), and the 103Pd source
      strength ranged from 1.3 to 1.6 mCi (median, 1.5 mCi). CT was performed within 4
      h after implantation. The dosimetric parameters analyzed included the percentage
      of the postimplant prostate volume covered by the 100%, 150%, 200%, and 300%
      prescription dose (V100, V150, V200, and V300, respectively). The median time to
      the last follow-up for patients without failure was 2.7 years. Freedom from
      biochemical failure was defined as a serum prostate-specific antigen level of <
      or =0.5 ng/mL at last follow-up. Patients were censored at last follow-up if
      their serum prostate-specific antigen level was still decreasing. RESULTS: The
      mean V100, V150, V200, and V300 value was 90% (+/-8%), 63% (+/-14), 35% (+/-13%),
      and 14% (+/-7%), respectively. Patients with a V100 of > or =90% had a 3-year
      freedom from biochemical failure rate of 96% vs. 87% for those with a V100 of
      <90% (p=0.0029). Overall, patients with more high-dose regions had a greater
      chance of biochemical control. However, when only patients with a V100 of > or
      =90% were analyzed, no relationship was found between higher dose regions and the
      likelihood of cancer control. This lack of effect on biochemical control was
      apparent for both isotopes. CONCLUSION: High-dose regions do not appear to affect
      cancer control rates, as long as >90% of the prostate volume is covered by the
      prescription dose.

PMID- 15850919
TI  - Patient subsets with T1-T2, node-negative breast cancer at high locoregional
      recurrence risk after mastectomy.
AB  - PURPOSE: To identify patient subsets with T1-T2N0 breast cancer at high risk of
      locoregional recurrence (LRR) who may warrant consideration for postmastectomy
      radiotherapy. METHODS AND MATERIALS: Data were analyzed for 1505 women referred
      between 1989 and 1999 with pathologic T1-T2N0M0 breast cancer treated with
      mastectomy with clear margins and no adjuvant radiotherapy. Logistic regression
      analysis was performed to identify statistically significant factors associated
      with LRR. Recursive partitioning was used to develop a classification tree model
      for LRR given the prognostic variables. RESULTS: The median follow-up was 7.0
      years. The 10-year Kaplan-Meier LRR rate was 7.8%. On logistic regression
      analysis, the statistically significant factors predicting LRR were histologic
      grade (p <0.0001), lymphovascular invasion (LVI) (p <0.0001), T stage (p = 0.05),
      and systemic therapy use (p = 0.01). In the recursive partitioning model, the
      first split in the classification tree was histologic grade. For 972 patients
      without high-grade histologic features, the 10-year Kaplan-Meier LRR rate was
      5.5%. For 533 patients with Grade 3 disease (LRR rate 12.1%), the concomitant
      presence of LVI was associated with a LRR rate of 21.2% (n = 126). In patients
      with Grade 3 disease without LVI, T2 tumors conferred a LRR rate of 13.4% (n =
      194), which increased to 23.2% for patients who did not receive systemic therapy
      (n = 63). CONCLUSION: Women with pT1-T2N0 breast cancer experienced a LRR risk of
      approximately 20% in the presence of Grade 3 disease with LVI or Grade 3 disease,
      T2 tumors, and no systemic therapy. These subsets of node-negative patients
      warrant consideration of for postmastectomy radiotherapy.

PMID- 15850920
TI  - 1998-1999 patterns of care study process survey of national practice patterns
      using breast-conserving surgery and radiotherapy in the management of stage I-II
      breast cancer.
AB  - PURPOSE: The Patterns of Care Study survey process evaluation has been an
      effective means of assessing the evaluation and treatment practices used by
      radiation oncologists in the United States for Stage I-II breast cancer. The
      current 1998-1999 report updates the previous 1989 and 1993-1994 analyses and
      reflects the recent changes in surgery and systemic therapy observed nationally
      in the management of early-stage disease. METHODS AND MATERIALS: A weighted
      sample size of 71,877 patient records of women treated with breast-conserving
      surgery and radiotherapy (RT) was obtained from a stratified two-stage sampling
      of 353 patient records. These cases were centrally reviewed from academic and
      private radiation oncology practices across the United States. The data collected
      included patient characteristics, clinical and pathologic factors, and surgical
      and RT details. The results were compared with those of previous Patterns of Care
      Study survey reports. RESULTS: Of the patients in the current survey, 97% had
      undergone mammography before biopsy. A review of the primary tumor pathologic
      findings indicated improved quantification of an intraductal component from 7.0%
      in 1993-1994 to 20.4% in 1998-1999 (p = 0.01). The tumor characteristics were
      better defined, with estrogen and progesterone receptor measurement performed in
      91.4% and 91.3% in the 1998-1999 survey vs. 83.7% and 80.3% in the 1989 survey,
      respectively (p = 0.03 and p = 0.002, respectively). Axillary dissection was
      performed in 82.2% in the present survey compared with 93.6% in the 1993-1994
      survey (p = 0.0004); sentinel node biopsy was performed in 20.1% of the present
      cases. The use of CT for planning was increased in the current survey, with 22.9%
      cases CT planned vs. 9% in 1993-1994 (p = 0.10). In the present survey, 100% had
      received whole breast RT. When a supraclavicular field was added, the dose was
      prescribed to a specified depth in 67.5% of cases, most commonly 3 cm. When an
      axillary field was added, the dose was generally prescribed to the mid-plane.
      Chemotherapy and tamoxifen was used in 36% and 55.8% of patients, respectively,
      in the 1998-1999 survey, representing a statistically significant increase
      compared with the 1993-1994 survey, despite comparable pathologic tumor size and
      nodal involvement. CONCLUSION: The present results demonstrate a high level of
      compliance of the sampled radiation oncology practices with current breast
      conservation standards and continued improvement in many categories compared with
      prior patterns of care study surveys. The estimates in the current survey after
      whole breast RT will serve as a benchmark against newer trends in breast cancer
      RT, such as partial breast RT.

PMID- 15850921
TI  - Results of breast conservation therapy from a single-institution community
      hospital in Hawaii with a predominantly Japanese population.
AB  - PURPOSE: To evaluate the outcome data from breast conservation therapy performed
      at the Kuakini Medical Center in Honolulu, Hawaii. The remarkably low rates of
      recurrence found in this study prompted a review of the literature and evaluation
      of the prognostic factors that may explain these results. METHODS AND MATERIALS:
      The data from patients with Tis, T1 or T2 breast tumors, treated with lumpectomy
      and radiotherapy during the 12-year period between January 1990 and December 2001
      were retrospectively reviewed and compared to results found in national
      publications. RESULTS: Current follow-up data was available in 97.1% of patients
      who met these criteria, identifying a total of 896 patients who were analyzed in
      this study. With a median follow-up exceeding 6 years, the local in-breast
      failure rate was 0.67%. Survival data was superior to the National Cancer Data
      Base for each stage of disease. CONCLUSION: This low rate of local relapse is
      extraordinary and unmatched by the published results generally cited in the
      literature. The findings are consistent with other studies reporting unusually
      low rates of breast cancer recurrence in patients of Japanese ancestry.

PMID- 15850922
TI  - Intensity-modulated radiotherapy for lymphoma involving the mediastinum.
AB  - PURPOSE: To determine the feasibility, potential advantage, and indications for
      intensity-modulated radiotherapy (IMRT) in the treatment of Hodgkin's lymphoma or
      non-Hodgkin's lymphoma involving excessively large mediastinal disease volumes or
      requiring repeat RT. METHODS AND MATERIALS: Sixteen patients with Hodgkin's
      lymphoma (n = 11) or non-Hodgkin's lymphoma (n = 5) undergoing primary
      radiotherapy or repeat RT delivered via an IMRT plan were studied. The
      indications for using an IMRT plan were previous mediastinal RT (n = 5) or
      extremely large mediastinal treatment volumes (n = 11). For each patient, IMRT,
      conventional parallel-opposed (AP-PA), and three-dimensional conformal (3D-CRT)
      plans were designed using 6-MV X-rays to deliver doses ranging from 18 to 45 Gy
      (median, 36 Gy). The plans were compared with regard to dose-volume parameters.
      The IMRT/AP-PA and IMRT/3D-CRT ratios were calculated for each parameter.
      RESULTS: For all patients, the mean lung dose was reduced using IMRT, on average,
      by 12% compared with AP-PA and 14% compared with 3D-CRT. The planning target
      volume coverage was also improved using IMRT compared with AP-PA but was not
      different from the planning target volume coverage obtained with 3D-CRT.
      CONCLUSION: In selected patients with Hodgkin's lymphoma and non-Hodgkin's
      lymphoma involving the mediastinum, IMRT provides improved planning target volume
      coverage and reduces pulmonary toxicity parameters. It is feasible for RT of
      large treatment volumes and allows repeat RT of relapsed disease without
      exceeding cord tolerance. Additional follow-up is necessary to determine whether
      improvements in dose delivery affect long-term morbidity and disease control.

PMID- 15850923
TI  - Hypoxia-induced radioresistance is independent of hypoxia-inducible factor-1A in
      vitro.
AB  - PURPOSE: We sought to determine whether hypoxia-induced radioresistance is
      mediated by the transcription factor hypoxia-inducible factor-1alpha (HIF
      1alpha). METHODS AND MATERIALS: We used 2 mouse embryonic fibroblast cell lines
      transformed with H-ras and TAg, 1 HIF-1alpha+/+ and the other HIF-1alpha-/-. Cell
      were exposed to either 95% air and 5% CO2 (normoxic conditions) or 0.2% O2, 94.8%
      N2, and 5% CO2 (hypoxic conditions) for 4 hours. Cells were then irradiated and
      subjected to clonogenic survival assays. RESULTS: Whereas neither +/+ ras/TAg nor
      -/- ras/TAg cells expressed HIF-1alpha under normoxic conditions, hypoxia induced
      expression of HIF-1alpha only in +/+ ras/TAg cells, confirming the absence of HIF
      1alpha in -/- ras/TAg cells. Clonogenic survival curves for +/+ ras/TAg and -/-
      ras/TAg cells under normoxia and hypoxia demonstrated that hypoxia increased
      radioresistance in both cell lines to the same degree. At 1-log cell kill, the
      +/+ ras/TAg and -/- ras/TAg cells had an identical oxygen enhancement ratio of
      1.28 +/- 0.09 and nearly identical oxygen enhancement ratios at 2-log cell kill.
      CONCLUSION: In our system of transformed mouse embryonic fibroblasts, hypoxia
      mediated radiation resistance is independent of HIF-1alpha.

PMID- 15850924
TI  - Dual responsive promoters to target therapeutic gene expression to radiation
      resistant hypoxic tumor cells.
AB  - PURPOSE: Tumor hypoxia is unequivocally linked to poor radiotherapy outcome. This
      study aimed to identify enhancer sequences that respond maximally to a
      combination of radiation and hypoxia for use in genetic radiotherapy approaches.
      METHODS AND MATERIALS: The influence of radiation (5 Gy) and hypoxia (1% O2) on
      reporter-gene expression driven by hypoxia (HRE) and radiation (Egr-1) responsive
      elements was evaluated in tumor cells grown as monolayers or multicellular
      spheroids. Hypoxia-inducible factor-1alpha (HIF-1alpha) and HIF-2alpha protein
      expression was monitored in parallel. RESULTS: Of the sequences tested, an HRE
      from the phosphoglycerate kinase-1 gene (PGK-18[5+]) was maximally induced in
      response to hypoxia plus radiation in all 5 cell lines tested. The additional
      radiation treatment afforded a significant increase in the induction of PGK
      18[5+] compared with hypoxia alone in 3 cell lines. HIF-1alpha/2alpha were
      induced by radiation but combined hypoxia/radiation treatment did not yield a
      further increase. The dual responsive nature of HREs was maintained when
      spheroids were irradiated after delivery of HRE constructs in a replication
      deficient adenovirus. CONCLUSIONS: Hypoxia-responsive enhancer element sequences
      are dually responsive to combined radiation and hypoxic treatment. Their use in
      genetic radiotherapy in vivo could maximize expression in the most radio
      resistant population at the time of radiation and also exploit microenvironmental
      changes after radiotherapy to yield additional switch-on.

PMID- 15850925
TI  - Modulation of radiation response by histone deacetylase inhibition.
AB  - PURPOSE: Histone deacetylase (HDAC) inhibitors, which modulate chromatin
      structure and gene expression, represent a class of anticancer agents that hold
      particular potential as radiation sensitizers. In this study, we examine the
      capacity of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) to modulate
      radiation response in human tumor cell lines and explore potential mechanisms
      underlying these interactions. METHODS AND MATERIALS: Cell proliferation:
      Exponentially growing tumor cells were incubated in medium containing 0-10 microM
      of SAHA for 72 h. Cells were fixed/stained with crystal violet to estimate cell
      viability. Apoptosis: Caspase activity was analyzed by fluorescence spectroscopy
      using a fluorescein labeled pan-caspase inhibitor. Cells were harvested after 48
      h of exposure to SAHA (1.0 microM), radiation (6 Gy), or the combination. Whole
      cell lysates were evaluated for poly(ADP-ribose) polymerase (PARP) cleavage by
      western blot analysis. Radiation survival: Cells were exposed to varying doses of
      radiation +/- 3 days pretreatment with SAHA (0.75-1.0 microM). After incubation
      intervals of 14-21 days, colonies were stained with crystal violet and manually
      counted. Immunocytochemistry: Cells were grown and treated in chamber slides. At
      specified times after treatment with SAHA, cells were fixed in paraformaldehyde,
      permeabilized in methanol, and probed with primary and secondary antibody
      solutions. Slides were analyzed using an epifluorescent microscope. RESULTS: SAHA
      induced a dose-dependent inhibition of proliferation in human prostate (DU145)
      and glioma (U373vIII) cancer cell lines. Exposure to SAHA enhanced radiation
      induced apoptosis as measured by caspase activity (p < 0.05) and PARP cleavage.
      The impact of SAHA on radiation response was further characterized using
      clonogenic survival analysis, which demonstrated that treatment with SAHA reduced
      tumor survival after radiation exposure. We identified several oncoproteins and
      DNA damage repair proteins (epidermal growth factor receptor, AKT, DNA-PK, and
      Rad51) that show differential expression after exposure to SAHA. These proteins
      may contribute to mechanistic synergy between HDAC inhibition and radiation
      response. CONCLUSION: These preclinical results suggest that treatment with the
      HDAC inhibitor SAHA can enhance radiation-induced cytotoxicity in human prostate
      and glioma cells. We are examining the capacity of HDAC inhibitors to modulate
      radiation response and tumor control in animal xenograft model systems to
      strengthen the rationale for future clinical trial exploration.

PMID- 15850926
TI  - Chronomodulation of topotecan or X-radiation treatment increases treatment
      efficacy without enhancing acute toxicity.
AB  - PURPOSE: Topotecan (TPT), a camptothecin analog, is currently used to treat human
      ovarian and small-cell lung cancer and is in clinical trials for other tumor
      sites. However, it is unknown whether chronomodulation of TPT treatment is
      beneficial. We examined the effects of administering TPT or X-radiation (XR)
      alone at different times of the day or night. METHODS: We treated mice bearing
      human colorectal tumor xenografts at four different times representing the early
      rest period (9 am or 3 HALO [hours after light onset]), late rest period (3 pm or
      9 HALO), early active period (9 pm or 15 HALO), and late active period (3 am or
      21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy,
      directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. RESULTS:
      Treatment with either TPT or XR at 3 am demonstrated the greatest efficacy
      (measured by a tumor regrowth assay) without significantly increasing acute
      toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely,
      treatment at 3 pm, in particular, showed increased toxicity without any enhanced
      efficacy. CONCLUSIONS: Our study provided the first evidence that
      chronomodulation of TPT treatments, consistent with the findings of other
      camptothecin analogs, is potentially clinically beneficial. Additionally, our
      findings suggest that chronomodulation of fractionated XR treatments is also
      potentially clinically beneficial.

PMID- 15850927
TI  - Influence of different breathing maneuvers on internal and external organ motion:
      use of fiducial markers in dynamic MRI.
AB  - PURPOSE: To investigate, with dynamic magnetic resonance imaging (dMRI) and a
      fiducial marker, the influence of different breathing maneuvers on internal organ
      and external chest wall motion. METHODS AND MATERIALS: Lung and chest wall motion
      of 16 healthy subjects (13 male, 3 female) were examined with real-time trueFISP
      (true fast imaging with steady-state precession) dMRI and a small inductively
      coupled marker coil on either the abdomen or thorax. Three different breathing
      maneuvers were performed (predominantly "abdominal breathing," "thoracic
      breathing," and unspecific "normal breathing"). The craniocaudal (CC),
      anteroposterior (AP), and mediolateral (ML) lung distances were correlated
      (linear regression coefficient) with marker coil position during forced and quiet
      breathing. RESULTS: Differences of the CC distance between maximum forced
      inspiration and expiration were significant between abdominal and thoracic
      breathing (p < 0.05). The correlation between CC distance and coil position was
      best for forced abdominal breathing and a marker coil in the abdominal position
      (r = 0.89 +/- 0.04); for AP and ML distance, forced thoracic breathing and a coil
      in the thoracic position was best (r = 0.84 +/- 0.03 and 0.82 +/- 0.03,
      respectively). In quiet breathing, a lower correlation was found. CONCLUSION: A
      fiducial marker coil external to the thorax in combination with dMRI is a new
      technique to yield quantitative information on the correlation of internal organ
      and external chest wall motion. Correlations are highly dependent on the
      breathing maneuver.

PMID- 15850928
TI  - Stereotactic radiosurgery for brain AVMs: role of interobserver variation in
      target definition on digital subtraction angiography.
AB  - PURPOSE: We evaluated the extent of interobserver variation in contouring
      arteriovenous malformations (AVMs) on digital subtraction angiography (DSA) with
      respect to volume, spatial localization, and dosimetry and correlated our
      findings with the clinical outcome. METHODS AND MATERIALS: Thirty-one patients
      who had undergone radiosurgery for brain AVMs were studied. Six clinicians
      independently contoured the nidus on the original DSA. As a measure of variation,
      the ratio between the volumes of agreement and the corresponding encompassing
      volumes, as well as the absolute positional shift between the individual target
      volumes were derived. Using the original treatment plan, the dosimetric coverage
      of the individually contoured volumes with standard collimators was compared with
      a similar plan using dynamic conformal arcs. RESULTS: The mean contoured nidus
      volume was 3.6 +/- 5.6 cm3. The mean agreement ratio was 0.45 +/- 0.18 for all
      possible pairs of observers. The mean absolute positional shift between
      individually contoured volumes was 2.8 +/- 2.6 mm. These differences were more
      marked in previously treated groups and tended to be more pronounced in those
      with treatment failure. The mean coverage of the individual volumes by the 80%
      prescription isodose was 88.1% +/- 3.2% using conventional collimators and 78.9%
      +/- 4.4% using dynamic conformal arcs (p = 0.001). CONCLUSION: Substantial
      interobserver variations exist when contouring brain AVMs on DSA for the purpose
      of radiosurgical planning. Such variations may result in underdosage to the AVM
      and, thereby, contribute to treatment failure. The consequences of contouring
      variations may increase with the use of more conformal radiosurgical techniques.

PMID- 15850930
TI  - Recent progress in defining mechanisms and potential targets for prevention of
      normal tissue injury after radiation therapy.
AB  - The ability to optimize treatments for cancer on the basis of relative risks for
      normal tissue injury has important implications in oncology, because higher doses
      of radiation might, in some diseases, improve both local control and survival. To
      achieve this goal, a thorough understanding of the molecular mechanisms
      responsible for radiation-induced toxicity will be essential. Recent research has
      demonstrated that ionizing radiation triggers a series of genetic and molecular
      events, which might lead to chronic persistent alterations in the
      microenvironment and an aberrant wound-healing response. Disrupted epithelial
      stromal cell communication might also be important. With the application of a
      better understanding of fundamental biology to clinical practice, new approaches
      to treating and preventing normal tissue injury can focus on correcting these
      disturbed molecular processes.

PMID- 15850931
TI  - Interleukin (IL)-1A and IL-6: applications to the predictive diagnostic testing
      of radiation pneumonitis.
AB  - PURPOSE: To explore the application of interleukin (IL)-1alpha and IL-6
      measurements in the predictive diagnostic testing for symptomatic radiation
      pneumonitis (RP). METHODS AND MATERIALS: In a prospective protocol investigating
      RP and cytokines, IL-1alpha and IL-6 values were analyzed by enzyme-linked
      immunosorbent assay from serial weekly blood samples of patients receiving chest
      radiation. We analyzed sensitivity, specificity, positive predictive value (PPV),
      and negative predictive value (NPV) over selected threshold values for both
      cytokines in the application to diagnostic testing. RESULTS: The average
      coefficient of variation was 51% of the weekly mean IL-1alpha level and 39% of
      the weekly mean IL-6 value. Interleukin 1alpha and IL-6 became positively
      correlated with time. Specificity for both cytokines was better than sensitivity.
      IL-6 globally outperformed IL-1alpha in predicting RP, with higher PPV and NPV.
      CONCLUSIONS: Our data demonstrate the feasibility of applying IL-1alpha and IL-6
      measurements of blood specimens to predict RP. Interleukin-6 measurements offer
      stronger positive predictive value than IL-1alpha. This application might be
      further explored in a larger sample of patients.

PMID- 15850932
TI  - Regulation of prostaglandin E2 synthesis after brain irradiation.
AB  - PURPOSE: A local tissue reaction, termed neuroinflammation, occurs after
      irradiation of brain tissue. Previous work suggested that cyclooxygenase (COX)-2
      activity was important for changes in gene expression associated with
      neuroinflammation as well as increased prostaglandin E2 (PGE2) levels seen after
      radiation treatment. METHODS AND MATERIALS: To begin to determine the
      contributions of other enzymes involved in PGE2 production, we examined protein
      levels of COX-1 and COX-2 as well as 2 PGE synthases (membrane and cytosolic
      PGES) 4 h after 35 Gy single dose irradiation to the brains of C3HeN mice. We
      also evaluated the effects of specific COX inhibitors on PGE2 production and PGES
      expression. RESULTS: As expected, COX-2 expression increased after radiation
      exposure. Brain irradiation also increased tissue protein levels for both PGES
      isoforms. Specific COX-2 inhibition with NS398 lowered brain PGE2 levels by about
      60%. Surprisingly, COX-1 inhibition with SC560 completely prevented the elevation
      of PGE2 seen after irradiation. Interestingly, NS398 reduced the membrane
      associated PGES isoform, whereas SC560 treatment lowered cytosolic isoform levels
      below those seen in unirradiated controls. CONCLUSIONS: Taken together, these
      data indicate that both cyclooxygenases contribute to PGE2 production in
      irradiated brain and reveal dependence of PGES isoforms expression on specific
      cyclooxygenase activities.

PMID- 15850933
TI  - Mechanism and modification of gastrointestinal soft tissue response to radiation:
      role of growth factors.
AB  - PURPOSE: The negative effects of radiation on the bowel critically limit the
      treatment doses possible for tumors in the abdomen. The purpose of the present
      study was to measure mRNA levels of inflammatory cytokines in abdominally
      irradiated mouse bowel. METHODS AND MATERIALS: Eight- to 12-week-old DBA mice
      were irradiated to the whole bowel in single fractions of 0 (mock irradiation),
      12.5, or 13.5 Gy, and sacrificed 18-25 weeks thereafter. Gross bowel reactions
      were scored for bowel retraction, bowel wall thickening, mesenteric
      telangiectasia, and petechia. Tissues were snap frozen and processed for RNase
      protection assay or reverse transcription polymerase chain reaction assay, or
      both. Transforming growth factor beta1 (TGFbeta1), TGFbeta2, TGFbeta3, tumor
      necrosis factor alpha, interleukin-6, and interferon gamma mRNA were measured.
      RESULTS: Radiation at 12.5 Gy and at 13.5 Gy produced significant bowel damage.
      Levels of all cytokines in irradiated mice were significantly increased (p <
      0.05). CONCLUSIONS: Late radiation-related bowel fibrovascular toxicity includes
      cytokine signal pathways that parallel those of many other normal tissues. These
      cytokine responses include elevations of tumor necrosis factor alpha, TGFbeta1,
      and interleukin-6. There exist approaches for lowering these cytokine levels that
      do not also protect tumor, and thus a therapeutic gain is expected. Opportunities
      to use these cytokine measurements both to predict clinical toxicity and to
      develop interventions are discussed.

PMID- 15850934
TI  - Molecular targets in radiation-induced blood-brain barrier disruption.
AB  - Disruption of the blood-brain barrier (BBB) is a key feature of radiation injury
      to the central nervous system. Studies suggest that endothelial cell apoptosis,
      gene expression changes, and alteration of the microenvironment are important in
      initiation and progression of injury. Although substantial effort has been
      directed at understanding the impact of radiation on endothelial cells and
      oligodendrocytes, growing evidence suggests that other cell types, including
      astrocytes, are important in responses that include induced gene expression and
      microenvironmental changes. Endothelial apoptosis is important in early BBB
      disruption. Hypoxia and oxidative stress in the later period that precedes tissue
      damage might lead to astrocytic responses that impact cell survival and cell
      interactions. Cell death, gene expression changes, and a toxic microenvironment
      can be viewed as interacting elements in a model of radiation-induced disruption
      of the BBB. These processes implicate particular genes and proteins as targets in
      potential strategies for neuroprotection.

PMID- 15850935
TI  - Fractionation and late rectal toxicity: no reliable estimates of alpha/beta value
      for rectum can be derived from studies where different volumes of rectum are
      irradiated at different dose levels: in regard to Brenner (Int J Radiat Oncol
      Biol Phys 2004;60:1013-1015.).

PMID- 15850937
TI  - Androgen Deprivation (AD) among low-risk and intermediate-risk prostate cancer
      patients: in regard to Ciezki et al. (Int J Radiat Oncol Biol Phys 2004;60:1347
      1350).

PMID- 15850938
TI  - A career pathway for radiation therapists. Does it really exist?: In regard to
      Kresl et al. (Int J Radiat Oncol Biol Phys 2004;60:8-14).

PMID- 15850940
TI  - Recommendations for image-based intracavitary brachytherapy of cervix cancer: the
      GYN GEC ESTRO Working Group point of view: in regard to Nag et al. (Int J Radiat
      Oncol Biol Phys 2004;60:1160-1172).

PMID- 15850943
TI  - Lack of survival benefit after stereotactic radiosurgery boost for glioblastoma
      multiforme: randomized comparison of stereotactic radiosurgery followed by
      conventional radiotherapy with carmustine to conventional radiotherapy with
      carmustine for patients with glioblastoma multiforme: report of radiation therapy
      oncology group 93-05 protocol: in regard to Souhami et al. (Int J Radiat Oncol
      Biol Phys 2004;60:853-860).

PMID- 15850944
TI  - Permanent alopecia after cranial irradiation: dose-response relationship: in
      regards to Lawenda et al. (Int J Radiat Oncol Biol Phys 2004;60:879-886).

PMID- 15850946
TI  - Radiobiological parameters suitable for modeling individual outcomes cannot be
      obtained by analyzing heterogeneous population data with homogeneous tumor
      control model: in regard to D'Souza et al. (Int J Radiat Oncol Biol Phys
      2004;58:1540-1548).

PMID- 15850948
TI  - Can a mathematical formula help define a radiation target volume using positron
      emission tomography? In regard to Black et al. (Int J Radiat Oncol Biol Phys
      2004;60:1272-1282).

PMID- 15850950
TI  - Axonal transport failure in neurodegenerative disorders: the case of Huntington's
      disease.

PMID- 15850951
TI  - [Circadian rhythms in the toxic effects of the histamine antagonist cetirizine in
      mice].
AB  - Cetirizine is a second generation histamine H(1) receptor antagonist used to
      provide symptomatic relief of allergic signs caused by histamine release. The aim
      of the study was to learn whether the survival and the motor incoordination
      (ataxia) side effect of cetirizine administration is dosing time-dependent.
      MATERIALS AND METHODS: A total of 240 male Swiss mice, 10 weeks of age were
      synchronized for 3 weeks by 12 h light (rest span)/12 h dark (activity span).
      Different doses of cetirizine were administered orally at fixed times during the
      day to determine both the sublethal (TD(50)) and lethal (LD(50)) doses, which
      were, respectively, 55 +/- 0.35 and 750 +/- 0.40 mg/kg. In the chronotoxicologic
      study a single dose of cetirizine (DL(50)) was administered to comparable groups
      of animals at six different circadian stages [1, 5, 9, 13, 17, 21 h after light
      onset (HALO)]. RESULTS: The survival was statistically significant dosing time
      dependent (chi(2) = 16.73; P < 0.001). Drug dosing at 17 HALO resulted in 83.3%
      survival rate whereas drug dosing at 5 HALO was only 23.25%. Cosinor analysis
      revealed a statistically significant circadian (period approximately 24 h)
      rhythmic component in survival. Lowest (20%) and highest (88%) ataxia occurred
      when cetirizine was administered, respectively, at 17 and 5 HALO. Cosinor
      analysis revealed a statistically significant circadian (period approximately 24
      h) rhythmic component in ataxia. CONCLUSION: Our results reveal that the best
      safety is shown when cetirizine is administered in the middle of the dark
      (activity) span of the mice, since it produces some side effects: ataxia and
      hyperthermia. Taking into account of the hour administration of cetirizine,
      improves treatment efficacy and permit the best control of allergic diseases.

PMID- 15850952
TI  - [Development of an experimental model for the study of the effects of cryotherapy
      on lung tumours].
AB  - Adenocarcinomas are today the most frequent lung cancers. They are mainly treated
      by surgery or by chemotherapy, but for the most advanced stages a local
      cryotherapy can be proposed as a palliative option for bronchial desobstruction.
      AIM OF THE STUDY: The aim of this work was to establish an experimental model to
      study in vivo the biological effects of this technique to propose it as a
      neoadjuvant treatment. MATERIALS AND METHODS: A xenograft system was used: cells
      from the A549 cell line were injected subcutaneously into SCID mice. Tumour nodes
      could be treated after seven weeks. The histological study showed that these
      tumours faithfully reproduced the morphological features of adenocarcinoma, and
      developed an intratumoral neovascularization. Two protocols of cryotherapy (1 vs
      3 cycles of freezing) were performed and the induction of apoptosis was analyzed
      by immunohistochemical staining of cleaved caspase-3. RESULTS: The basal
      expression of cleaved caspase-3 in untreated tumours (23%) increased after
      cryotherapy. The increase was maximal eight hours after treatment (up to 47% of
      positive cells) and was less important with the first protocol, suggesting a
      lesser efficiency in the induction of apoptosis. CONCLUSION: The establishment of
      this model, which is faithful to physiological features, allowed us to
      demonstrate in vivo time and dose-dependent effects of cryotherapy.

PMID- 15850953
TI  - Tissue transglutaminase antibodies in celiac disease, comparison of an enzyme
      linked immunosorbent assay and a dot blot assay.
AB  - AIMS: The purpose of our study is to determine the sensitivity, specificity and
      predictive values of an enzyme linked immunosorbent assay (ELISA) and a dot blot
      assay for the detection of IgA class anti-tissue transglutaminase antibodies (IgA
      AtTGA) and to compare these results with those of IgA class anti-endomysium
      antibodies (IgA-AEA), IgA class anti-reticulin antibodies (IgA-ARA) and IgA class
      anti-gliadin antibodies (IgA-AGA). PATIENTS: Serum samples from 143 patients (97
      children, 46 adults) with untreated celiac disease (CD) confirmed by intestinal
      biopsy and 74 disease controls (64 children, 10 adults) were studied. Methods. -
      The anti-tissue transglutaminase antibodies were detected by dot blot assay and
      an ELISA using guinea pig tissue transglutaminase (gp-tTG) as antigen. The anti
      endomysium antibodies were detected by an indirect immunofluorescence technique
      on cryostat sections of human umbilical cord. The anti-reticulin antibodies were
      also investigated by indirect immunofluorescence on cryostat sections of kidney,
      liver and stomach of rat. The anti-gliadin antibodies were determined by an
      ELISA. RESULTS: The sensitivity of an ELISA for the detection of anti-tissue
      transglutaminase antibodies was 86% in children and 87% in adults and the
      sensitivity of dot blot assay was 57% in children and 54% in adults. The
      specificity of an ELISA and dot blot for the detection for anti-tissue
      transglutaminase antibodies was, respectively, 96% and 88% lower than that of
      anti-endomysium antibodies (100%). The sensitivity of anti-gliadin antibodies was
      97% in children and 91% in adults and their specificity was 85%. The sensitivity
      of anti-reticulin antibodies was 94% in children and 87% in adults. Their
      specificity was 100%. CONCLUSIONS: The sensitivity and specificity of an ELISA
      for the detection of anti-tissue transglutaminase antibodies were better than
      that of dot blot assay. However, this dot blot assay could screen four celiac
      patients who have not had anti-tissue transglutaminase antibodies by an ELISA.
      The sensitivity of anti-endomysium antibodies was better than that of anti-tissue
      transglutaminase antibodies, anti-reticulin antibodies and anti-gliadin
      antibodies but in children aged less than 2 years, the sensitivity of anti
      gliadin antibodies was better than that of anti-tissue transglutaminase
      antibodies.

PMID- 15850954
TI  - [Shelf-lives of morphine and pethidine solutions stored in patient-controlled
      analgesia devices: physico-chemical and microbiological stability study].
AB  - Morphine and meperidine in Patient-Controlled Analgesic devices are commonly used
      to treat chronic pain patients. These devices deliver a programmed amount of drug
      and allow self-administration by the patient depending on the pain. In our
      department of pharmacy, 300 devices were manufactured in 2003. The aim of this
      study was to assess their shelf-life. The devices were filled aseptically and
      without preservatives with 1 and 40 mg/ml morphine solution and 5 and 20 mg/ml
      meperidine and stored over 30 days at room temperature and protected from light.
      Culture assay of the solutions showed that they remained sterile for 30 days. No
      turbidity of any solutions from samples collected twice a week was noticed. pH
      and osmolarity remained constant. Drug concentrations were determined using
      stability indicating HPLC method, as we showed that degradation products can be
      separated from the drugs. Little loss of meperidine occurred within 21 days (<5%)
      and morphine concentration, which increased, because of solvent evaporation,
      remained lower than 5% within 21 days but increased up to 10% after 30 days. No
      traces of degradation products (pseudomorphine or pethidic acid) were detected.
      The physicochemical and microbiological stability of morphine and meperidine
      hydrochlorides stored in such devices has been established for 21 days at room
      temperature and protected from light.

PMID- 15850955
TI  - [Lipid profile in maintenance haemodialysis].
AB  - INTRODUCTION: The chronic kidney failure is a source of dyslipidemia and
      accelerated atherosclerosis. No changes in the lipoprotein profile could be
      reversed by dialysis. OBJECTIVE: Our aim was to study the lipid disturbances
      characteristics in end stage renal disease in order to assess their theorical
      atherogenic potential. SUBJECTS AND METHODS: The patient population consisted of
      36 patients on maintenance haemodialysis. Matched control subjects were recruited
      among apparently healthy normolipidemic Tunisians. Total cholesterol,
      triglycerides, high-density-lipoprotein cholesterol, low-density-lipoprotein
      cholesterol, apolipoprotein AI and apolipoprotein B concentrations were measured.
      RESULTS: The triglycerides levels were significantly higher in patient group,
      unlike the high-density-lipoprotein cholesterol and apolipoprotein AI levels that
      were significantly reduced. We saw no increase in the levels of low-density
      lipoprotein cholesterol and apolipoprotein B. The low-density-lipoprotein
      cholesterol/high-density-lipoprotein cholesterol ratio result wasn't helpful in
      the evaluation of the atherogenic risk. CONCLUSION: We confirm the quantitative
      lipid disorders associated with maintenance haemodialysis. The assessment of
      cardiovascular risk on the basis of these disorders seems difficult.

PMID- 15850956
TI  - [Screening tests for animal TSE: present and future].
AB  - In 1999, three rapid tests (Prionics, Bio-Rad, Enfer) have been validated by the
      European Commission for the post-mortem diagnosis of BSE in cattle. They are now
      used on a large scale over the entire Europe. In absence of antibodies
      specifically recognizing the native conformation PrPres, its selective
      determination is based on the biochemical properties of this abnormal form (PK
      resistance, aggregation in presence of detergents). In addition, all these tests
      include a denaturation step so that PrP can be detected by appropriate
      antibodies. When applied on "risk populations" or on "healthy animals" entering
      into the human food chain, these rapid tests have provided a better estimation of
      the epizootic and allowed an efficient removal of animals bearing a risk for
      human consumption. Since 2002, they have also been used for the post-mortem
      diagnosis of scrapie in sheep and goat. Five new tests have been recently
      evaluated (ID-Lelystad; Perkin-elmer, Prionics Check LIA, UCSF, Imperial college)
      but it is too early to know which place they will take in the field. Current
      tests allow a preclinical diagnosis of TSE, especially in sheep and goats for
      which a very early detection is possible in peripheral lymphoid tissues. However,
      to date, no test on living animal has been validated. Taking into account the
      important number of research teams now involved on this topic one may expect
      spectacular progress in the forthcoming years.

PMID- 15850957
TI  - [Bovine spongiform encephalopathy].
AB  - The identification of variant Creutzfeldt-Jakob disease (vCJD) in human strongly
      reinforced the perception of risks associated with the infectious agent involved
      in Bovine Spongiform Encephalopathy (BSE). The development of rapid tests for the
      diagnosis of BSE by the detection of the abnormal prion protein allowed a huge
      increase in surveillance of the cattle disease. This first revealed a higher
      prevalence of the infection than previously believed. However, food safety
      measures, mainly based on the ban of the use of meat and bone meal in ruminants
      and the elimination of specified risk materials from the food chain, already
      allowed significant progress in the control of the cattle disease, especially in
      the United Kingdom. Nevertheless, the diagnosis can still not be obtained in the
      live animal, while the disease only appears following a several years incubation
      period. Another major issue is the identification of the BSE agent when it has
      been transmitted to another species. This question not only arises in veterinary
      medicine, with the major question of a possible infection of small ruminants by
      the BSE agent, but also in human in which the existence of other forms of the
      disease linked to the BSE agent but possibly differing from Creutzfeldt-Jakob
      disease cannot be excluded.

PMID- 15850958
TI  - [Hospital practice and prion risks].
AB  - Procedures applicable in France for the prevention of prion diseases were first
      implemented in 1995, resulting from the threat of an epidemic extension of
      Creutzfeldt-Jakob Disease (CJD) following contamination resulting from the use of
      extracted growth hormone. It was found later that the bovine disease could infect
      humans via foodstuffs, and the human variant of the disease (v-CJD) transmissible
      through lymphoid formations was described in 1996. This led to generalizing
      precautions to a larger number of medical interventions, taking into account the
      risk for a population more broadly exposed to contamination. The principles for
      managing these new risks are described, as well for the use of medical devices or
      in patient as pathology laboratories.

PMID- 15850959
TI  - [Prion protein and copper: a mysterious relationship].
AB  - Prion diseases form a group of fatal neurodegenerative disorders including
      Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in
      animals. All of which are characterized by the accumulation of abnormally folded
      isoform of the cellular prion protein (PrP(C)), denoted PrP(Sc), which is the
      major component of infectious prion diseases. The function of PrP(C) remains
      elusive. Its amino-terminal region contains a repeated five octapeptide domain
      that binds copper. The protein is believed to display a superoxide dismutase like
      activity, and hence a possible protective function against oxidative stress. In
      this review, relationship between PrP, copper and oxidative stress was analysed.
      Thus, metal ions and oxidative stress would play an essential role in the
      pathogenesis of prion diseases and represent important targets for future
      therapeutic targets or a novel diagnostic marker.

PMID- 15850960
TI  - Serum albumin and clinical outcome in pediatric cardiac surgery.
AB  - OBJECTIVE: We evaluated the behavior of serum albumin concentrations in response
      to metabolic stress that is associated with cardiac surgery and the role of this
      protein as a predictor of clinical outcome in children at high surgical risk who
      undergo operative correction of congenital heart defects. METHODS: Serum albumin
      concentrations were measured in 30 children who had heart disease and were at
      high surgical risk. Analyses were performed before surgery, on the second
      postoperative day, and on discharge from the intensive care unit. Preoperative
      serum concentrations of albumin were compared with those of a control group that
      consisted of 20 healthy and well-nourished children. RESULTS: Preoperative
      albumin concentrations of patients were lower than those of the control group
      (3.4+/-0.25 g/dL versus 4.0+/-0.18 g/dL, P<0.05). Serum levels decreased on the
      second postoperative day and at discharge from the intensive care unit (3.1+/
      0.65 g/dL and 3.2+/-0.44 g/dL, P<0.05) compared with preoperative concentrations.
      Preoperative concentrations lower than 3.0 g/dL were associated with increased
      postsurgical infection (P=0.0026) and with increased mortality (P=0.0138).
      Patients whose postoperative levels were lower than 3.0 g/dL had longer hospital
      stays compared with those whose concentrations were higher than 3.0 g/dL (14.5+/
      1.3 d versus 10+/-2.2 d, P<0.05). CONCLUSION: The results suggest that
      hypoalbuminemia is common among children who have heart disease and are at high
      surgical risk, and serum albumin concentrations lower than 3 g/dL may be related
      to outcome in the period after cardiac surgery.

PMID- 15850961
TI  - Diet and eating habits in high and low socioeconomic groups.
AB  - OBJECTIVE: We measured the difference of dietary intake and eating habits across
      socioeconomic statuses (SESs) in Israel. METHODS: Participants were randomly
      recruited from three high SES municipalities and three low SES municipalities in
      the Negev. Participants were interviewed at home with 24-h food questionnaires
      that included additional questions regarding health and eating habits. Nutrient
      and energy intakes were compared between groups, as were major contributors to
      the energy and food groups. RESULTS: One hundred sixteen participants from the
      high SES group and 206 from the low SES entered the study. Those in the low SES
      group were older, heavier, less educated, and less physically active. Dietary
      intake among the participants in the low SES group was significantly lower in
      protein, monounsaturated fat, and most vitamins and minerals (thiamine,
      riboflavin, niacin, vitamin C, calcium, magnesium, and iron). Conversely, vitamin
      E intake was higher in the low SES group. In the low SES group, the main
      contributors to energy intake were breads, oils, and sugars. Oils, fats, and
      citrus fruits were consumed more among subjects in the low SES group, whereas
      dairy products, grains, and legumes were consumed less by subjects in the high
      SES group. CONCLUSION: In a detailed survey conducted in two distinct
      populations, we found poorer diet quality in the low SES group. The root causes
      for such divergence need further study. As smoking declines in the modern world,
      nutrition will become the key risk factor in many diseases. Further research and
      educational and legislative initiatives are needed to curtail this risk.

PMID- 15850962
TI  - Bioimpedance electrical spectroscopy in the first six months of life: some
      methodologic considerations.
AB  - OBJECTIVES: The objectives of this study were to evaluate the feasibility of
      using multifrequency bioelectrical impedance spectroscopy (BIS) in newborns and
      first-semester infants and to assess the influence of diverse methodologic and
      biological factors on BIS measurements. METHODS: We studied 69 infants of both
      sexes, from the first day after birth through age 6 mo. They were healthy term
      infants who had no congenital malformations and were born in a low-income, peri
      urban neighborhood of Guatemala City. The design was based on serial, repeated
      BIS measurements. RESULTS: Overall mean values of extra- and intracellular
      resistance (mean+/-standard deviation) were 470.0+/-73.3 Omega and 604.6+/-179.2
      Omega, respectively. We found statistical differences in both resistances in
      relation to advancing age and degree of movement while taking the measurements.
      With respect to repeat measurements by two separate observers, interobserver
      differences were a non-significant 7.6 Omega for both resistances. Restraining
      the infants and previous consumption of milk or formula had a significant effect
      on extracellular resistance measurements. The mean standard errors of measurement
      was 4.5 Omega for extracellular resistance and 73.9 Omega for intracellular
      resistance. CONCLUSION: The BIS technique is feasible in newborn and young
      children when physiologic and methodologic aspects are respected or controlled.

PMID- 15850963
TI  - Serum selenoprotein-P levels in patients with inflammatory bowel disease.
AB  - OBJECTIVE: Selenoprotein-P is a selenium-rich serum protein that carries more
      than 50% of serum selenium. We evaluated changes in serum selenoprotein-P levels
      in patients with inflammatory bowel disease. METHODS: Serum selenoprotein-P
      levels were measured by enzyme-linked immunosorbent assay. Twenty healthy
      individuals (controls), 34 patients with ulcerative colitis, and 37 patients with
      Crohn's disease (CD) were studied. RESULTS: A highly significant correlation was
      found between the serum selenium and selenoprotein-P levels. There was no
      significant difference in serum selenoprotein-P levels between healthy controls
      (average 3.4+/-0.8 microg/mL, n=20) and patients with ulcerative colitis (3.0+/
      1.0 microg/mL, n=34). Serum selenoprotein-P levels were significantly lower in
      patients with CD (average 1.8+/-0.5 microg/mL, n=37). Serum selenoprotein-P
      levels were significantly lower in the elemental diet group of patients who had
      CD (average 1.4+/-0.4 microg/mL, n=17) than in the non-elemental diet group of
      patients who had CD (average 2.1+/-0.3 microg/mL, n=20). CONCLUSION: We found
      that the serum selenoprotein-P level is decreased in patients with CD. It may be
      a useful marker to monitor the systemic selenium status in various disorders.

PMID- 15850964
TI  - Testing various herbs for antithrombotic effect.
AB  - OBJECTIVE: Prevention of arterial thrombotic diseases has high priority in
      developed countries. Because people who eat inappropriate food are prone to
      thrombotic events, regular intake of an antithrombotic diet may offer a
      convenient and effective way of prevention. The aim of the present study was to
      find herbs that have antithrombotic effects. METHODS: Herbs were crushed and
      centrifuged and the juice obtained was filtered. The effect of filtrate on
      platelet-rich thrombus formation was assessed by a shear-induced in vitro
      platelet function test (hemostatometry). Filtrates showing significant
      antithrombotic activity were further assessed by using a laser-induced in vivo
      thrombosis test in mice. The effect of orally administered herb filtrates on flow
      mediated vasodilation was also measured. RESULTS: Common thyme and rosemary
      showed significant antithrombotic activity in vitro and in vivo. Neither herb
      affected flow-mediated vasodilation. CONCLUSION: Some herbs possess
      antithrombotic effects in experimental models of thrombosis. The mechanism of the
      antithrombotic effect of common thyme and rosemary may involve a direct
      inhibitory effect on platelets.

PMID- 15850965
TI  - Eicosapentaenoic acid modulates the immune response but has no effect on a mimic
      of antigen-specific responses.
AB  - OBJECTIVE: It has been suggested that the omega-3 polyunsaturated fatty acid
      eicosapentaenoic acid (EPA) has immunosuppressive effects and that these may be
      detrimental in some circumstances. Many studies have used high-fat diets or have
      concentrated on one aspect of immune function, such as mitogen-induced
      proliferation. In the present study we assessed the effect of high-purity EPA
      provided as a novel diester with propane-1,3-diol, which was delivered orally
      within the normal dietary fat content. METHODS: Mitogen-induced proliferation and
      a mimic of antigen-specific splenocyte proliferation were examined.
      Proinflammatory cytokine production in response to lipopolysaccharide ex vivo was
      also measured. Balb/c mice were fed a fat-free diet to which was added oil to
      make up 5% of the final diet weight by using corn oil or 95% pure EPA as a
      diester with propane-1,3-diol (4%, plus 1% corn oil). RESULTS: There was no
      difference in food consumption or weight gain between mice fed the control and
      EPA-enriched diets for 10 or 24 d. There was a significant decrease in the
      splenocyte proliferation index in animals fed the EPA-enriched diet after 10 and
      24 d when stimulated by concanavalin A (P<0.05), but no difference when cells
      were stimulated with anti-CD3 and interleukin-2. There was a significant increase
      in the production of tumor necrosis factor by splenocytes of mice fed the EPA
      enriched diet when stimulated by lipopolysaccharide (P<0.0005). However, there
      was no difference in ex vivo lipopolysaccharide-stimulated production of
      interleukin-6 between the two diets at either time point (P>0.05). CONCLUSIONS:
      The present study found that, rather than producing a generalized
      immunosuppression, the administration of approximately 10 g of EPA/kg of body
      weight has more subtle effects in modulating the immune system. The observed
      effects of EPA may explain some of its reported beneficial effects in
      inflammatory conditions without producing detrimental effects on antigen-specific
      immunosurveillance.

PMID- 15850966
TI  - Ingested cocoa can prevent high-fat diet-induced obesity by regulating the
      expression of genes for fatty acid metabolism.
AB  - OBJECTIVE: We previously found that ingested cocoa decreased visceral adipose
      tissue weight in rat. To elucidate the molecular mechanisms of that effect, we
      carried out experiments aimed at analyzing biochemical parameters and gene
      expression profiles. METHODS: Rats were fed either of two high-fat diets,
      differing only in supplementation with real or mimetic cocoa. On day 21, body
      weights, mesenteric white adipose tissue weights, and concentrations of serum
      triacylglycerol were measured. To investigate the molecular mechanisms underlying
      the effects of cocoa on lipid metabolism and triacylglycerol accumulation, we
      examined gene expression profiles in liver and mesenteric white adipose tissues
      using the GeneChip microarray system. RESULTS: Final body weights and mesenteric
      white adipose tissue weights were significantly lower in rats fed the real cocoa
      diet than in those fed the mimetic cocoa diet (P<0.05), and serum triacylglycerol
      concentrations tended to be lower in rats fed the real cocoa diet (P=0.072). DNA
      microarray analysis showed that cocoa ingestion suppressed the expression of
      genes for enzymes involved in fatty acid synthesis in liver and white adipose
      tissues. In white adipose tissue, cocoa ingestion also decreased the expression
      of genes for fatty acid transport-relating molecules, whereas it upregulated the
      expression of genes for uncoupling protein-2 as a thermogenesis factor.
      CONCLUSIONS: Ingested cocoa can prevent high-fat diet-induced obesity by
      modulating lipid metabolism, especially by decreasing fatty acid synthesis and
      transport systems, and enhancement of part of the thermogenesis mechanism in
      liver and white adipose tissue.

PMID- 15850967
TI  - Bifidogenic effect of dietary fiber and resistant starch from leguminous on the
      intestinal microbiota of rats.
AB  - OBJECTIVES: The bifidogenic effect of leguminous containing diets on the
      intestinal microbiota of male Wistar rats was studied. METHODS: Isoprotein
      (12.2+/-0.3%) and isoenergetic (373.2+/-4.2 kcal/100 g) experimental diets, whose
      sources of dietary fiber and resistant starch were pea (Pisum sativum, L.),
      common bean (Phaseolus vulgaris, L.), chickpea (Cicer arietinum, L.), and lentil
      (Lens culinaris, Med.), and a control diet (casein+microcrystalline cellulose)
      were offered ad libitum to recently weaned male albino Wistar rats (16
      rats/treatment) for 28 d. Cecal appendices were removed and analyzed for
      Bifidobacterium, Lactobacillus, Enterobacter, Bacteroides, Clostridium, and total
      anaerobes. RESULTS: The common bean diet showed the highest content of dietary
      fiber (17.0+/-0.2 g/100 g), which was significantly different (P<0.05) from the
      others. Resistant starch content was similar for all diets. The control and
      chickpea groups showed significantly higher consumption of diet and food
      conversion efficiency than the others. The leguminous-containing diets produced a
      larger mass of cecal material that was statistically different from the control
      group. The pea group presented the highest count of Bifidobacterium (9.4+/-0.7
      log colony-forming units per gram of raw material), which was significantly
      different from the others, and the Lactobacillus count was similar for all
      groups. Animals fed leguminous-containing diets showed lower counts of
      Enterobacter and Bacteroides than did the control group and no statistical
      difference (P>0.05) was found between groups with respect to counts of
      Clostridium and total anaerobes. CONCLUSIONS: The pea and chickpea groups stood
      out from the others with respect to growth of Bifidobacterium, especially the pea
      group.

PMID- 15850968
TI  - Sodium and calcium intakes and bone mass in rats revisited.
AB  - OBJECTIVE: High sodium intake accompanied by insufficient dietary calcium may
      have detrimental effects on bone mass. Our study evaluated the effects of
      increased sodium and decreased calcium intakes on bone mineral density (BMD) and
      bone mineral content (BMC) in rats. METHODS: Four-month-old female Wistar rats
      were given deionized water or 1.8% solution of sodium chloride in deionized water
      and fed normal (1.2%) or marginal (0.33%) calcium in the diet for 2 mo. At the
      end of the experiment, BMD and BMC of the whole body and urinary sodium and
      calcium excretion were evaluated. All rats were killed and right femurs were
      removed to assess dry and ash weights. Two-way analysis of variance was used to
      evaluate effect of salt intake and effect of dietary calcium on these parameters.
      RESULTS: Salt-loaded animals had greater water consumption during the entire 2-mo
      period and significantly lower body weight from week 5 of the experiment. High
      salt intake increased urine volume and urinary excretion of sodium and calcium.
      Urinary calcium was about five times higher in salt-loaded animals than in rats
      on deionized water irrespective of dietary calcium content. Calcium in diet
      itself had no significant effect on these parameters. High salt intake slightly,
      but not significantly, decreased BMD, BMC, and femur weights. Lower calcium in
      diet significantly decreased BMD, and its effect on femur ash weight almost
      reached a level of significance. CONCLUSION: We confirmed the benefit of adequate
      calcium intake to BMD. Under our experimental condition, high salt intake in rats
      for 2 mo had no statistically significant effect on femur weights, BMD, or BMC
      even with marginal calcium in the diet.

PMID- 15850969
TI  - Effect of supplemental L-arginine on the function of T lymphocytes and the
      formation of advanced glycosylated end products in rats with streptozotocin
      induced diabetes.
AB  - OBJECTIVE: We investigated the effect of supplemental L-arginine on lymphocyte
      function in diabetes and its association with suppressed formation of advanced
      glycosylated end products (AGEs). METHODS: For the in vivo study, rats with
      streptozotocin-induced (65 mg/kg of body weight, intravenously) diabetes were
      treated with or without 2% L-arginine or glycine (as a positive control) in
      drinking water for 8 wk. We then measured serum fructosamine concentrations and
      concanavalin A-induced proliferative ability of lymphocytes from these animals.
      For the in vitro study, AGEs derived from albumin were prepared by incubating D
      glucose (200 mmol/L) and bovine serum albumin (100 mg/mL) at 37 degrees C for 2
      wk in the presence or absence of L-arginine (0.1-10 mmol/L). These preparations
      were quantified for their bovine serum albumin--derived AGE content, and their
      effect on concanavalin A-induced proliferative activity of T lymphocyte from
      normal rats was measured. RESULTS: Serum fructosamine concentrations were
      significantly higher in the diabetic rats than in the control rats (P<0.05) but
      were significantly lowered with L-arginine supplementation (P<0.05). The lower
      lymphocyte proliferation rate found in the diabetic rats was reversed by
      supplemental L-arginine (P<0.05). During the course of incubation of bovine serum
      albumin with D-glucose, the presence of L-arginine prevented the formation of
      bovine serum albumin-derived AGEs and attenuated their inhibitory effect on the
      rate of lymphocyte proliferation in a dose-dependent manner. CONCLUSION:
      Supplemental L-arginine improved the function of T lymphocytes in diabetic rats
      in association with decreased formation of AGEs.

PMID- 15850970
TI  - Maitake D-Fraction enhances antitumor effects and reduces immunosuppression by
      mitomycin-C in tumor-bearing mice.
AB  - OBJECTIVE: D-Fraction, a polysaccharide extracted from maitake mushrooms (Grifola
      frondosa), has been reported to exhibit an antitumor effect through activation of
      immunocompetent cells, including macrophages and T cells, with modulation of the
      balance between T-helper 1 and 2 cells. We examined whether D-Fraction could
      decrease the effective dosage of the chemotherapeutic agent, mitomycin-C (MMC),
      necessary to control carcinoma in mice. METHODS AND RESULTS: We determined that
      0.25 mg.kg-1.d-1 was the optimal dosage of MMC because consecutive administration
      for 17 d resulted in antitumor effects and a survival ratio of 100% in mice
      bearing mammary cancer cells (MM-46). Although the dosage of MMC was lower than
      the effective level, spleen weight and total number of nuclear cells in the mouse
      spleen decreased, indicating that MMC showed immunosuppressive activity. In
      contrast, the combination of D-Fraction and MMC recovered the decreases in the
      dose response induced by MMC and inhibited tumor cell growth more than MMC alone.
      These effects were achieved through increased immunocompetent cell proliferation.
      We evaluated the expression of CD28 on splenic CD8+ T cells and the amount of
      interleukin-12 produced by whole spleen cells including macrophages after
      administering D-Fraction. The results showed enhancement of the T-helper 1
      dominant response. CONCLUSION: These results suggest that D-Fraction can decrease
      the effective dosage in tumor-bearing mice by increasing the proliferation,
      differentiation, and activation of immunocompetent cells and thus provide a
      potential clinical benefit for patients with cancer.

PMID- 15850971
TI  - Adult blindness secondary to vitamin A deficiency associated with an eating
      disorder.
AB  - OBJECTIVE: We examined an adult patient who lost one eye due to severe
      keratomalacia secondary to self-induced vitamin A deficiency. METHODS: This case
      report provides a clinical, ophthalmologic, and laboratory description in
      addition to a review of the medical literature. RESULTS: A 33-y-old woman with a
      17-y history of an eating disorder presented with bilateral conjunctival xerosis,
      an infected corneal ulcer in the right eye and a large descemetocele in the left
      eye. Laboratory and clinical findings were consistent with vitamin A deficiency.
      Despite a tectonic penetrating keratoplasty, her left eye perforated and had to
      be eviscerated. In parallel, vitamin A replacement improved her clinical status
      and the ocular findings in her right eye. CONCLUSIONS: The present report
      indicates that vitamin A deficiency secondary to eating disorders should be
      considered in the differential diagnosis of patients with severe dry eye and
      corneal ulceration.

PMID- 15850972
TI  - Television health promotion in four countries.
AB  - OBJECTIVE: The research plan was to conduct a comparative, longitudinal field
      experiment in Russia, Hungary, the Czech Republic, and Poland to evaluate the
      effect of a nutritional and general health promotion television series. The
      series addressed four health topics: a healthy diet, avoidance of tobacco use and
      alcohol abuse, and enhanced physical activity. METHODS: Because of different
      infrastructure and contingency conditions in the four countries, data collection
      ranged from group-administered surveys at a central location to individual
      personal interviews using a quasi-experiment comparing viewers and non-viewers 18
      y and older. It occurred between 1996 and 1998. RESULTS: Overall, the television
      programs were found to provide new, useful, and practical information to viewers.
      Most (53.4% to 64.0%) learned useful information. Nearly 33% or more (29.5% to
      37.9%) intended to change their lifestyle, with about 25% or more (24.0% to
      60.2%) of this group indicating that they would eat more fruits and vegetables.
      Subsequently, 16.7% to 45.0% reported actual dietary changes consistent with
      health promotion. CONCLUSIONS: The study addressed diet and nutritional patterns
      in this region and the underlying social and behavioral factors, topics on which
      there is very limited information. Methodologic equivalence was sought through
      consistent measures despite the differential research infrastructure in the four
      countries. Results indicated that viewers rated the nutritional and general
      health promotion television programs favorably and that media messages can be
      used to motivate and educate viewers. More sustained television programs focused
      on health promotion will benefit audiences in Central and Eastern Europe.

PMID- 15850973
TI  - Exelixis: integrated drug-discovery and development platform for human
      therapeutics.

PMID- 15850974
TI  - Biotin synthase: enzyme or reactant?
AB  - Biotin synthase catalyzes formation of a thiophane ring through a radical
      mechanism that is difficult to reconstitute in vitro. Choi-Rhee and Cronan
      measure a turnover of 20-60 equivalents of biotin in vivo, but also find that
      turnover renders the protein susceptible to proteolytic destruction.

PMID- 15850975
TI  - Tissue transglutaminase inhibition.
AB  - Khosla and coworkers report the synthesis of peptidic dihydroisoxazole
      derivatives, the in vitro evaluation of these novel compounds as inhibitors of
      recombinant human tissue transglutaminase (TG2), and their oral bioavailability
      and efficacy for the synergistic treatment of glioblastoma tumors.

PMID- 15850976
TI  - Mitochondria give cells a tan.
AB  - The discovery of melanogenin, a small molecule that induces pigmentation in
      melanocytes, has led to identification of a mitochondrial protein as target. The
      finding is relevant therapeutically, and argues for how chemical biology can be
      used to elucidate organelle-specific functions.

PMID- 15850977
TI  - Target identification for a promising anti-lupus drug.
AB  - Target identification is one of the more difficult aspects of modern chemical
      genetics. In this issue of Chemistry & Biology, Johnson et al. provide a
      compelling case for going through the trouble. As a byproduct of their
      identification of the cellular target of an anti-lupus compound, they have
      uncovered a powerful tool for the characterization of a fascinating molecular
      machine, the F1F0-ATP synthase.

PMID- 15850978
TI  - Bioactive peptides from libraries.
AB  - New ligands for a variety of biological targets can be selected from biological
      or synthetic combinatorial peptide libraries. The use of different libraries to
      select novel peptides with potential therapeutic applications is reviewed. The
      possible combination of molecular diversity provided by combinatorial libraries
      and a rational approach derived from computational modeling is also considered.
      Advantages and disadvantages of different approaches are compared. Possible
      strategies to bypass loss of peptide bioactivity in the transition from ligand
      selection to in vivo use are discussed.

PMID- 15850979
TI  - Mirror-image packing in enantiomer discrimination molecular basis for the
      enantioselectivity of B.cepacia lipase toward 2-methyl-3-phenyl-1-propanol.
AB  - Synthetic chemists often exploit the high enantioselectivity of lipases to
      prepare pure enantiomers of primary alcohols, but the molecular basis for this
      enantioselectivity is unknown. The crystal structures of two phosphonate
      transition-state analogs bound to Burkholderia cepacia lipase reveal this
      molecular basis for a typical primary alcohol: 2-methyl-3-phenyl-1-propanol. The
      enantiomeric alcohol moieties adopt surprisingly similar orientations, with only
      subtle differences that make it difficult to predict how to alter
      enantioselectivity. These structures, along with a survey of previous structures
      of enzyme bound enantiomers, reveal that binding of enantiomers does not involve
      an exchange of two substituent positions as most researchers assumed. Instead,
      the enantiomers adopt mirror-image packing, where three of the four substituents
      at the stereocenter lie in similar positions. The fourth substituent, hydrogen,
      points in opposite directions.

PMID- 15850980
TI  - Switching between allosteric and dimerization inhibition of HIV-1 protease.
AB  - Refining the functional groups on a phenethylamine moiety within an inhibitor of
      HIV-1 protease led to a switch in the mechanism of inhibition from competitive
      and allosteric to dimerization inhibition. Phenylether extensions to the
      phenethylamine group led to agents that target the dimerization interface of HIV
      1 protease with high potency.

PMID- 15850981
TI  - A regioselective tryptophan 5-halogenase is involved in pyrroindomycin
      biosynthesis in Streptomyces rugosporus LL-42D005.
AB  - The antibiotic compound pyrroindomycin B contains an indole ring chlorinated in
      the 5 position. The indole ring is probably derived from tryptophan, and thus
      primers derived from conserved regions of tryptophan halogenases were used to
      amplify and clone a DNA fragment that was then used to isolate a tryptophan 5
      halogenase gene (pyrH) from a cosmid library of the pyrroindomycin producer
      Streptomyces rugosporus LL-42D005. A gene disruption mutant in the tryptophan 5
      halogenase gene no longer produced pyrroindomycin B, but still produced
      pyrroindomycin A, the nonhalogenated derivative. The halogenase gene could be
      overexpressed in Pseudomonas fluorescens BL915 DeltaORF1 and was purified to
      homogeneity by immobilized metal chelate ion affinity chromatography.
      Chlorinating and brominating activities with tryptophan as a substrate were
      detected in cell-free extracts and for the purified enzyme.

PMID- 15850982
TI  - Identification of a carotenoid oxygenase synthesizing acyclic xanthophylls:
      combinatorial biosynthesis and directed evolution.
AB  - A carotenoid desaturase homolog from Staphylococcus aureus (CrtOx) was
      identified. When expressed in engineered E. coli cells synthesizing linear C(30)
      carotenoids, polar carotenoid products were generated, identified as aldehyde and
      carboxylic acid C(30) carotenoid derivatives. The major product in this
      engineered pathway is the fully desaturated C(30) dialdehyde carotenoid 4,4'
      diapolycopen-4,4'-dial. Very low carotenoid yields were observed when CrtOx was
      complemented with the C(40) carotenoid lycopene pathway. But extension of an in
      vitro evolved pathway of the fully desaturated 2,4,2',4'-tetradehydrolycopene
      produced the structurally novel fully desaturated C(40) dialdehyde carotenoid
      2,4,2',4'-tetradehydrolycopendial. Directed evolution of CrtOx by error-prone PCR
      resulted in a number of variants with higher activity on C(40) carotenoid
      substrates and improved product profiles. These findings may provide new
      biosynthetic routes to highly polar carotenoids with unique spectral properties
      desirable for a number of industrial and pharmaceutical applications.

PMID- 15850983
TI  - Biotin synthase is catalytic in vivo, but catalysis engenders destruction of the
      protein.
AB  - Biotin synthase is responsible for the synthesis of biotin from dethiobiotin and
      sulfur. Although the name of the protein implies that it functions as an enzyme,
      it has been consistently reported that biotin synthase produces <1 molecule of
      biotin per molecule of protein in vitro. Moreover, the source of the biotin
      sulfur atom has been reported to be the [2Fe-2S] center of the protein. Biotin
      synthase has therefore been designated as a substrate or reactant rather than an
      enzyme. We report in vivo experiments demonstrating that biotin synthase is
      catalytic but that catalysis puts the protein at risk of proteolytic destruction.

PMID- 15850984
TI  - Chemistry and biology of dihydroisoxazole derivatives: selective inhibitors of
      human transglutaminase 2.
AB  - 3-halo-4,5-dihydroisoxazoles are attractive warheads for the selective inhibition
      of nucleophilic active sites in biological systems. A series of 3-bromo-4,5
      dihydroisoxazole compounds were prepared and tested for their ability to
      irreversibly inhibit human transglutaminase 2 (TG2), an enzyme that plays an
      important role in the pathogenesis of diverse disorders including Celiac Sprue
      and certain types of cancers. Several compounds showed high specificity for human
      TG2 (k(inh)/K(I) > 2000 min(-1)M(-1)) but essentially no reactivity (k < 1 min(
      1)M(-1)) toward physiological thiols such as glutathione. The pharmacokinetic and
      pharmacodynamic properties of a prototype dihydroisoxazole inhibitor, 1b, were
      evaluated; in mice the compound showed good oral bioavailability, short serum
      half-life and efficient TG2 inhibition in small intestinal tissue, and low
      toxicity. It also showed excellent synergism with N,N'-bis(2-chloroethyl)-N
      nitrosourea (BCNU, carmustine) against refractory glioblastoma tumors in mice. A
      fluorescent dihydroisoxazole inhibitor 5 facilitated microscopic visualization of
      TG2 endocytosis from the extracellular surface of HCT-116 cells. Together, these
      findings demonstrate the promise of dihydroisoxazole compounds as probes for the
      biology of TG2 and its role in human disease.

PMID- 15850985
TI  - Dissection of melanogenesis with small molecules identifies prohibitin as a
      regulator.
AB  - Bioactive compounds can be used to selectively modulate gene function. We
      utilized a chemical genetic approach to dissect the mammalian pigmentation
      pathway and identify protein regulators. We screened a tagged library of 1170
      small molecules in a cell-based assay and discovered a class of pigment-enhancing
      chemicals. From this class we characterized the small molecule melanogenin. Using
      melanogenin bound to an affinity matrix and amino acid sequencing, we identified
      the mitochondrial protein, prohibitin, as an intracellular binding target.
      Studies employing siRNA demonstrate that prohibitin is required for melanogenin
      to exert its propigmentary effects and reveal an unsuspected functional role for
      this protein in melanin induction. This represents a mechanism by which
      propigmentary signals are transduced and ultimately provides a potential target
      for the treatment of pigmentary disorders.

PMID- 15850987
TI  - Factors involved in progression to chronicity of mechanical low back pain.

PMID- 15850986
TI  - Identification and validation of the mitochondrial F1F0-ATPase as the molecular
      target of the immunomodulatory benzodiazepine Bz-423.
AB  - Bz-423 is a 1,4-benzodiazepine that suppresses disease in lupus-prone mice by
      selectively killing pathogenic lymphocytes, and it is less toxic compared to
      current lupus drugs. Cells exposed to Bz-423 rapidly generate O(2)(-) within
      mitochondria, and this reactive oxygen species is the signal initiating
      apoptosis. Phage display screening revealed that Bz-423 binds to the oligomycin
      sensitivity conferring protein (OSCP) component of the mitochondrial F(1)F(0)
      ATPase. Bz-423 inhibited the F(1)F(0)-ATPase in vitro, and reconstitution
      experiments demonstrated that inhibition was mediated by the OSCP. This target
      was further validated by generating cells with reduced OSCP expression using RNA
      interference and studying the sensitivity of these cells to Bz-423. Our findings
      help explain the efficacy and selectivity of Bz-423 for autoimmune lymphocytes
      and highlight the OSCP as a target to guide the development of novel lupus
      therapeutics.

PMID- 15850988
TI  - Current pharmacological treatment for fibrous dysplasia and perspectives for the
      future.

PMID- 15850989
TI  - Dual inhibition of cyclo-oxygenases and 5-lipoxygenase: a novel therapeutic
      approach to inflammation?

PMID- 15850990
TI  - Androgens and bone metabolism.
AB  - The gradual reductions in bone mass and skeletal calcium density seen throughout
      adulthood occur in parallel with changes in the production of bioactive sex
      hormones in both men and women. The long-held belief that osteoporosis is
      dependent on androgens in men and estrogens in women has been challenged by
      recent reports of osteoporosis in young men with normal testosterone levels but
      extremely low estrogen levels. A review of the literature indicates that
      estrogens have a far greater influence on bone mass than do androgens. This may
      suggest new approaches to the treatment of male osteoporosis. Furthermore,
      osteoporosis induced by prostate cancer treatment should receive greater medical
      attention.

PMID- 15850991
TI  - LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass
      disorders.
AB  - The LDL receptor-related protein 5 (LRP5) is a member of the LDL receptor family,
      which also includes the VLDL receptor and the apolipoprotein E receptor 2. The
      LRP5 is a co-receptor of Wnt located on the osteoblast membrane between two other
      receptors, Frizzled and Kremen. Frizzled and LRP5 bind to Wnt, thereby
      stabilizing beta-catenin and activating bone formation. When the dickkopf protein
      (Dkk) binds to Kremen and LRP5, this last undergoes internalization and therefore
      becomes unable to bind Wnt; this leads to degradation of beta-catenin and to
      inhibition of bone formation. In humans, loss of LRP5 function causes
      osteoporosis-pseudoglioma syndrome, which is characterized by congenital
      blindness and extremely severe childhood-onset osteoporosis (lumbar spine Z-score
      often < -4) with fractures. The G171V mutation prevents Dkk from binding to LRP5,
      thereby increasing LRP5 function; the result is high bone mass due to uncoupling
      of bone formation and resorption. The Z-scores in this condition can exceed +6 at
      the hip and spine. The LRP5 and Wnt/beta-catenin reflect the level of bone
      formation and play a central role in bone mass accrual and normal distribution.
      Furthermore, LRP5 may contribute to mediate mechanical loads within bone tissue.
      Identification of the Wnt/beta-catenin pathway is a breakthrough in the
      elucidation of pathophysiological mechanisms affecting bone tissue and suggests
      new treatment targets for patients with osteoporosis or specific malignant
      conditions such as myeloma and sclerotic bone metastases.

PMID- 15850992
TI  - Bone loss and teeth.
AB  - Loss of teeth results in irreversible alveolar bone resorption, and untreated
      dental disease causes alveolar bone lysis that ultimately leads to loss of teeth.
      In addition to anchoring the teeth in the alveolar ridge, the maxillary and
      mandibular bone allows dental restoration procedures, such as construction of
      root-supported implants, fixed dentures, or removable dentures. However, the
      functional and cosmetic results depend on the quantity and quality of the
      maxillary or mandibular bone, which can be affected by many normal and abnormal
      processes. The alveoli are particularly fragile and labile. Changes in alveolar
      bone vary considerably across individuals and depend directly on local factors.
      Many studies have investigated associations between alveolar bone status and bone
      mass at other skeletal sites. These studies focused chiefly on the course of
      parodontal disease, alveolar ridge resorption after tooth extraction, and density
      differences across various mandibular sites. They produced conflicting results,
      probably because of differences in measurement methods. Measurement sites and
      methods should be standardized to ensure that reliable and comparable data are
      obtained. To date, there are few reliable methods for obtaining quantitative
      measurements of bone mineral content in maxillary and mandibular bone.

PMID- 15850994
TI  - Structural evaluation in the management of patients with rheumatoid arthritis:
      development of recommendations for clinical practice based on published evidence
      and expert opinion.
AB  - OBJECTIVES: To develop French evidence-based recommendations for the structural
      evaluation of rheumatoid arthritis (RA) in everyday practice. METHODS: A
      scientific committee selected 10 questions using the Delphi consensus procedure.
      Evidence-based responses to each question were sought by searching the PubMed and
      Ovid databases and the abstract databases for the 2002, 2003, and 2004 annual
      meetings of the French Society for Rheumatology, the EULAR, and the American
      College of Rheumatology. The following indexing terms were used: rheumatoid
      arthritis, arthritis, patient, diagnostic imaging, radiography, joint, erosion,
      and joint space width. All articles published in French or English prior to May
      2004 were identified. The evidence from these articles was reported to a panel of
      77 rheumatologists working in hospital or office practice. The panel developed
      detailed recommendations, filling gaps in evidence with their expert opinion. The
      strength of each recommendation was determined. RESULTS: The 10 questions probed
      the structural evaluation of RA by plain radiography, magnetic resonance imaging
      (MRI), and ultrasonography, both for diagnostic and monitoring purposes. The
      literature search retrieved 673 publications, of which 166 were selected and
      reviewed. The panel developed 10 recommendations, one for each question, which
      were accepted by consensus. CONCLUSION: Recommendations relative to the diagnosis
      or monitoring of structural involvement in patients with RA in everyday practice
      were developed. They should help to improve practice uniformity and, ultimately,
      to improve the management of RA.

PMID- 15850993
TI  - Physical examination and laboratory tests in the management of patients with
      rheumatoid arthritis: development of recommendations for clinical practice based
      on published evidence and expert opinion.
AB  - OBJECTIVES: To develop recommendations for the physical and laboratory-test
      follow-up of patients with rheumatoid arthritis (RA) seen in everyday practice,
      using evidence from the literature, supplemented with expert opinion when needed.
      METHODS: A scientific committee selected 7-10 questions using the Delphi
      consensus procedure. Evidence-based responses to each question were sought in the
      literature and were then used by a panel to develop recommendations. To fill in
      gaps in knowledge from the literature, the panelists relied on their personal
      opinion. RESULTS: The seven questions dealt with the physical and laboratory-test
      follow-up of RA and the factors predicting disease severity. The literature
      review identified 799 articles whose title and abstract suggested relevance to
      the study. Elimination of articles that provided no data on the study topic left
      128 original articles. The panel developed seven recommendations, one for each
      question, which were accepted by consensus. CONCLUSION: Recommendations about the
      physical and laboratory-test follow-up of patients with RA seen in everyday
      practice were developed. Because they constitute an objective foundation built by
      consensus among experts, should improve the uniformity and quality of care
      provided to RA patients in everyday practice.

PMID- 15850995
TI  - Impact of osteoarthritis: results of a nationwide survey of 10,000 patients
      consulting for OA.
AB  - The clinical burden of osteoarthritis (OA) is difficult to assess because of the
      substantial variability between patients. OBJECTIVE: Evaluate the human
      consequences of OA in patients. METHODS: In 2000, a nationwide survey was
      conducted among a sample of more than 5000 physicians (90.3% general
      practitioners and 9.7% rheumatologists), representative of French physicians.
      Each recruited the first two patients consulting for hip, knee, or hand OA after
      the survey began. The functional limitation rates were compared with those for
      age- and sex-matched controls obtained from the 1999 population-based national
      survey on disability (HID survey). RESULTS: Clinical and demographic information
      was obtained for 10,412 OA patients (mean-age 66.2 years, sex ratio F:M 1.96).
      The OA diagnosis was based on both clinical and radiographic findings for 84.5%.
      More than 80% of all patients reported limitations in their activities of daily
      living, either for basic tasks, leisure activities, or work. OA patients were
      substantially more limited than controls: the standardised limitation rate ratios
      (SLRR) were 6.0 (95% confidence interval: 5.9:6.1) for mobility outside the home,
      2.1 (2.0:2.1) for house cleaning, 1.6 (1.5:1.8) for dressing oneself, and 1.6
      (1.5:1.8) for sports. Of the 17.6% of OA patients and 17.5% of the controls still
      working, 64.4% and 14.3%, respectively, were limited in their job duties, for a
      SLRR of 4.5 (4.3:4.7). CONCLUSION: This study shows that OA-related disability
      has a significant impact on the retired as well as on those still involved in the
      labour market.

PMID- 15850996
TI  - Asymmetry of small joint involvement in rheumatoid arthritis: prevalence and
      tendency towards symmetry over time.
AB  - OBJECTIVES: To quantify asymmetry of radiological joint damage in rheumatoid
      arthritis (RA), to determine whether asymmetrical damage to joints in RA becomes
      symmetrical over time, and to identify factors predictive of symmetrization.
      METHODS: In phase 1, initial, mid-term (mean follow-up: 3 years) and late (mean
      follow-up: 8 years) radiographs of 48 patients with definite RA (English
      population) were graded by the Modified Larsen (ML) system. In phase 2, 27
      subjects (Canadian population) with at least one asymmetrical pair of joints in
      the hands or feet were identified. Two successive radiographs of 77 asymmetrical
      joints, separated by at least 2 years, were compared. Clinical and biological
      factors were assessed for their ability to predict symmetrization, defined as a
      reduction in side-to-side difference over time of two or more ML grades. RESULTS:
      In phase 1, the overall rate of asymmetry was 12.9% (95% CI: 11.2-14.5%),
      increasing from 9.7% (first visit) to 13.8% (mid-term) and 14.4% (last visit).
      Metacarpophalangeal (MCP) joints were more frequently asymmetrical than thumb
      (MCP and interphalangeal) joints (P = 0.0064) and proximal interphalangeal (PIP)
      joints (P < 0.0001); wrist quadrants were more frequently asymmetrical than PIP
      joints (P < 0.0001). In phase 2, two groups were identified and compared:
      symmetrizers (22 joints) and non-symmetrizers (55 joints). The overall
      probability of small joints in the hand and foot symmetrizing was 28.5%.
      Rheumatoid factor (RF) was predictive of symmetrization. The risk of
      symmetrization was significantly increased in RF-positive patients with
      asymmetric joints (P = 0.01). The prevalence of asymmetry did not decrease with
      disease duration, despite symmetrization. CONCLUSIONS: Prevalence of asymmetry in
      joint damage in RA was 13-16%. Symmetry was more evident in PIP joints than in
      MCP and wrist joints. Seropositive patients are more than twice as likely to
      symmetrize than seronegative patients. Data regarding the tendency for
      symmetrization may have value in the clinical management of RA patients with
      asymmetrical joint damage.

PMID- 15850997
TI  - Aseptic discitis in patients with ankylosing spondylitis: a retrospective study
      of 14 cases.
AB  - OBJECTIVES: To determine whether patients with ankylosing spondylitis (AS) and
      discitis exhibit specific characteristics as compared to patients who have AS
      without discitis. METHODS: We retrospectively collected clinical, laboratory, and
      imaging data from the charts of 79 patients with AS admitted to a rheumatology
      department. RESULTS: Of the 79 patients, 14 (18%) had discitis that was not due
      to infection or trauma. Mean age at the diagnosis of AS was 40 years and mean
      duration of AS at admission was 10 years, with no difference between the two
      groups. In three patients, discitis was the inaugural manifestation of AS. Two
      patients had discitis at two levels. The lumbar and thoracolumbar segments were
      the most common sites of discitis. Symptoms of discitis were present in 10 of the
      14 patients. Stage III sacroiliitis was significantly more common in the patients
      with discitis. None of the patients experienced neurological compromise.
      CONCLUSION: The frequency of aseptic discitis in patients with AS is probably
      overestimated as a result of inclusion and exclusion biases. Discitis usually
      occurs at an advanced stage of AS under the form of an erosive condition related
      to both mechanical factors and osteoporosis. Inaugural or early discitis can
      occur, however, as a result of the inflammatory process.

PMID- 15850998
TI  - Prevalence and factors associated to low back pain among hospital staff.
AB  - OBJECTIVES: Because of its frequency and consequences on professional life, low
      back pain (LBP) represents a real health care problem. Our study is aimed at
      determining the prevalence of LBP among hospital staff, analyzing the medical and
      professional consequences as well as investigating into the factors associated to
      this health problem. METHODS: We have conducted an inquiry among 350 employees at
      Fattouma Bourguiba teaching hospital. The employees have answered a pre
      established questionnaire including 51 items. RESULTS: The cumulative life
      prevalence was 57.7% of the cases. The annual prevalence was 51.1% of the cases.
      Chronic LBP prevalence was 12.8% of the cases. Medical care was required in 61.9%
      of the cases. Radiological explorations were performed in 45% of the cases. Sick
      leave was observed in 26.1% of the cases and an occupational change was necessary
      in two cases. Factors associated to LBP were age (P <0.01), female gender (P =
      0.024), high BMI (P = 0.01), the fact of being married or divorced (P < 0.01),
      smoking (P = 0.016), past medical LBP history (P < 0.0001), extra professional
      activity (P < 0.01), migraine (P < 0.001), years' service (P = 0.007) as well as
      heavy weight lifting (P = 0.008). Exercise is rather a protecting factor against
      LBP (P = 0.019). CONCLUSION: The prevalence of LBP among hospital staff as well
      as the socio-professional drawbacks is important. Many factors are associated to
      LBP urging medical teams to take some preventive measures to reduce this
      affliction.

PMID- 15850999
TI  - Tonic dystonia: an uncommon complication of reflex sympathetic dystrophy
      syndrome. A review of five cases.
AB  - Tonic dystonia is an underrecognized complication of reflex sympathetic dystrophy
      syndrome (RSDS) characterized by an increase in muscle tone at the site of
      injury. Case-reports.- We describe five cases of tonic dystonia complicating RSDS
      of the lower extremity. There were four women and one man, with a mean age of 52
      years. In addition to the typical features of RSDS, the patients had fixed
      equinovarus of the foot with hyperextension or hyperflexion of the great toe. In
      two patients, examination after spinal anesthesia showed that the deformity was
      reducible. Spontaneous resolution of the dystonia occurred in one patient.
      Another patient failed to experience meaningful improvement after a motor block
      followed by botulinic toxin injections. In two patients, the same treatment was
      followed by a slight improvement. Treatment options are still being evaluated in
      the last patient. Discussion.- Tonic dystonia is an underrecognized complication
      of RSDS that often develops after a minor injury yet causes prolonged pain and
      disability. Spread of the dystonia to other sites is not infrequent. The
      underlying mechanisms remain unclear but may involve dysfunction of the central
      or peripheral nervous system or psychogenic factors. Suggested treatments include
      motor block, intrathecal baclofen, sympathetic block, and sympathectomy. However,
      none of these treatments has been proved effective. Conclusion.- The five cases
      described here provide useful information on RSDS-associated tonic dystonia, a
      condition that runs a protracted course and remains difficult to manage.

PMID- 15851000
TI  - Disseminated extrapulmonary tuberculosis revealed by humeral osteomyelitis with
      chronic unremarkable pain.
AB  - Disseminated extrapulmonary tuberculosis is uncommon, particularly among
      immunocompentent individuals. We report the case of a 38-year-old woman from the
      Ivory Coast who had osteomyelitis in the right humerus, a cold abscess in the
      pectoralis major muscle, T11 spondylitis, deep lymphadenopathies, peritoneal
      nodules, and hepatitis. She had no evidence of immune deficiency, and her only
      risk factor for tuberculosis was her origin from an endemic area. The outcome was
      favorable after treatment with antitubercular drugs. This case illustrates the
      recent changes in the epidemiology of tuberculosis in France, where the incidence
      among immigrants is rising. It also serves as a reminder that tuberculosis can
      run a chronic and extremely insidious course. At diagnosis, our patient had a 2
      year history of chronic pain in her right shoulder and back, suggestive of a
      minor mechanical disorder.

PMID- 15851001
TI  - Cystic hygroma in the quadriceps muscle: a sanguine diagnosis for knee pain.
AB  - Reported here is a 28-year-old female who presented with severe right knee pain
      and swelling nearby the joint. Ultrasonography, magnetic resonance imaging and
      eventually surgery were performed. She was diagnosed to have a cystic hygroma in
      the vastus lateralis muscle. This is the first patient of a cystic hygroma in the
      quadriceps muscle.

PMID- 15851002
TI  - Cervical spondylotic myelopathy in athetoid cerebral palsy patients: about five
      cases.
AB  - We herein report five cases of cerebral palsy athetosic patients with spondyloid
      cervical myelopathy. Four of them underwent decompressive surgery. The level of
      cervicarthrosis differs from a control population with a more frequent
      osteoarthritis on the lower cervical spine. The diagnosis of spondylotic cervical
      myelopathy is frequently overlooked because of the insidious progression of
      neurologic disorders and of the pre-existent neurological handicap. Depressive
      syndrome is often evoked in such a situation, and thus responsible for a delay of
      diagnosis. The presence of an hypersignal in T2 MRI sequences is still
      controversial. For some authors it is an indication for surgery, which is the
      treatment with the best functional results. CONCLUSION: Cervical spondylotic
      myelopathy must be evoked in patients with athetoid cerebral palsy who complain
      about a decrease of their functional ability.

PMID- 15851003
TI  - Anomalies of vertebrae and ribs: Jarcho Levin syndrome. Description of a case and
      literature review.
AB  - Jarcho Levin syndrome is a congenital disorder characterized by the presence of
      rib and vertebral defects at birth. This syndrome is usually diagnosed in
      newborns with short neck and trunk and short stature. They present multiple
      vertebral anomalies at different levels of the spine, including "butterfly
      vertebrae", hemivertebrae and fused hypoplastic vertebrae. The small size of the
      thorax in newborns frequently leads to respiratory compromise and death in
      infancy. We report a new case with short trunk and neck and vertebral and costal
      anomalies without respiratory problems. A literature review was conducted.

PMID- 15851004
TI  - Helping RNAi deliver.

PMID- 15851005
TI  - In utero gene therapy: current challenges and perspectives.
AB  - Over the past few years, considerable progress in prenatal diagnosis and surgery
      combined with improvements in vector design vindicate a reappraisal of the
      feasibility of in utero gene therapy for serious monogenetic diseases. As adult
      gene therapy gathers pace, several apparent obstacles to its application as a
      treatment may be overcome by pre- or early postnatal treatment. This review will
      examine the concepts and practice of prenatal vector administration. We aim to
      highlight the advantages of early therapeutic intervention focusing on diseases
      that could benefit greatly from a prenatal gene therapy approach. We will pay
      special attention to the strategies and vectors that are most likely to be used
      for this application and will speculate on their expected developments for the
      near future.

PMID- 15851006
TI  - Aptamers directed to HIV-1 reverse transcriptase display greater efficacy over
      small hairpin RNAs targeted to viral RNA in blocking HIV-1 replication.
AB  - RNA molecules can be powerful inhibitors of HIV-1 replication. To determine the
      relative efficacy of siRNAs and RNA aptamers, a direct comparison of three anti
      HIV reverse transcriptase aptamers and three shRNAs targeted to HIV-1(R3b) was
      made. U6 promoter-driven anti-HIV genes were delivered into CEMx174 cells via a
      retroviral vector, and transduced cells were sorted out via green fluorescent
      protein function and challenged with HIV. The results show that, at low virus
      input, shRNAs can block HIV as efficiently as aptamers. When expressed in target
      cells, both classes of inhibitors blocked early events of reverse transcription,
      suggesting they are both able to access intracellular reverse transcription
      complexes. However, at higher multiplicities of infection (m.o.i. of 50), while
      the aptamers could efficiently inhibit HIV replication, shRNAs did not. RNase
      protection assays indicated similar steady-state levels or nucleocytoplasmic
      distribution showing that the differential efficacy was not a reflection of
      intracellular concentration. The higher potency of anti-RT aptamers could be due
      to their ability to inhibit two successive rounds of reverse transcription owing
      to their unique ability to be encapsidated into virion particles. Furthermore,
      anti-RT aptamers expressed in T cells afforded protection against high-dose
      infection by chimeric RT-SHIV viruses.

PMID- 15851007
TI  - Retargeting mobile group II introns to repair mutant genes.
AB  - Retroposable elements such as retroviral and lentiviral vectors have been
      employed for many gene therapy applications. Unfortunately, such gene transfer
      vectors integrate genes into many different DNA sequences and unintended
      integration of the vector near a growth-promoting gene can engender pathological
      consequences. For example, retroviral vector-mediated gene transfer induced
      leukemia in 2 of 11 children treated for severe combined immunodeficiency,
      raising significant safety issues for gene transfer strategies that cannot be
      targeted to specific sequences. Here, we examine the use of a mobile retroposable
      genetic element that can be targeted to introduce therapeutic sequences site
      specifically into mutant genes. The data demonstrate that the mobile group II
      intron from Lactococcus lactis can be targeted to insert into and repair mutant
      lacZ (approved gene symbol GLB1) and beta-globin (approved gene symbol HBB) genes
      with high efficiency and fidelity in model systems in bacteria. These results
      suggest that these mobile genetic elements represent a novel class of agents for
      performing targeted genetic repair.

PMID- 15851008
TI  - A direct comparison of two nonviral gene therapy vectors for somatic integration:
      in vivo evaluation of the bacteriophage integrase phiC31 and the Sleeping Beauty
      transposase.
AB  - In this study we performed a head-to-head comparison of the integrase phiC31
      derived from a Streptomyces phage and the Sleeping Beauty (SB) transposase, a
      member of the TC1/mariner superfamily of transposable elements. Mouse liver was
      cotransfused with a vector containing our most robust human coagulation factor IX
      expression cassette and the appropriate recombinase recognition site and either a
      phiC31- or a SB transposase-expressing vector. To analyze transgene persistence
      and to prove somatic integration in vivo we induced cell cycling of mouse
      hepatocytes and found that the transgene expression levels dropped by only 16 to
      21% and 56 to 66% in mice that received phiC31 and SB, respectively. Notably, no
      difference in the toxicity profile was detected in mice treated with either
      recombinase. Moreover we observed that with the integrase-mediated gene transfer,
      transgene expression levels were dependent on the remaining noncoding vector
      sequences, which also integrate into the host genome. Further analyses of a hot
      spot of integration after phiC31-mediated integration revealed small chromosomal
      deletions at the target site and that the recombination process was not dependent
      on the orientation in which the phiC31 recognition site attached to the pseudo
      recognition sites in the host genome. Coupled together with ongoing improvements
      in both systems this study suggests that both nonviral vector systems will have
      important roles in achieving stable gene transfer in vivo.

PMID- 15851009
TI  - Systemic administration of attenuated Salmonella choleraesuis in combination with
      cisplatin for cancer therapy.
AB  - Some anaerobic and facultative anaerobic bacteria have been employed as
      anticancer agents. Previously, we have demonstrated tumor-targeting and antitumor
      activities of attenuated Salmonella choleraesuis carrying antiangiogenic genes.
      Here we exploited S. choleraesuis as a single-agent therapy and as part of a
      combination therapy with low-dose cisplatin for syngeneic murine lung tumor and
      hepatoma. Systemically injected S. choleraesuis preferentially accumulated within
      tumors for at least 4 weeks and the bacteria accumulated preferentially in not
      only subcutaneous but also orthotopic tumors over livers and spleens at ratios
      ranging from 1000:1 to 100,000:1. S. choleraesuis was capable of delaying tumor
      growth and enhancing survival in both subcutaneous tumor and experimental
      metastasis models. More strikingly, the combination of S. choleraesuis plus
      cisplatin acted additively to retard tumor growth and extensively prolong the
      survival time of the mice bearing hepatomas or lung tumors. Such combination
      treatment also increased infiltrating neutrophils and CD8+ T cells, as well as
      apoptotic cells, in the tumors, compared with S. choleraesuis or cisplatin
      treatment alone. These findings suggest that S. choleraesuis in combination with
      cisplatin, which exerts oncolytic effects and enhances antitumor immune
      responses, represents a promising strategy for the treatment of primary and
      metastatic tumors.

PMID- 15851010
TI  - Melanoma differentiation-associated gene-7 protein physically associates with the
      double-stranded RNA-activated protein kinase PKR.
AB  - We previously reported that adenoviral-mediated overexpression of the melanoma
      differentiation-associated gene-7 (Ad-mda7; approved gene symbol IL24) leads to
      the rapid induction of PKR and activation of its downstream targets, resulting in
      apoptosis induction in human lung cancer cells. To evaluate the mechanism by
      which Ad-mda7 activates PKR, we studied the interaction between MDA-7 and PKR
      proteins. Following Ad-mda7 transduction of lung cancer cells, intracellular and
      extracellular MDA-7 protein was generated, leading to dose- and time-dependent
      PKR induction. Purified MDA-7 protein administered extracellularly did not induce
      PKR or apoptosis, suggesting that Ad-mda7-mediated PKR activation and apoptosis
      were not dependent on extracellular MDA-7 protein. Following Ad-mda7
      transduction, RT-PCR demonstrated no increase in PKR mRNA levels despite
      increased levels of PKR protein, suggesting posttranscriptional regulation of PKR
      by MDA-7. Immunofluorescence and coimmunoprecipitation studies demonstrated that
      MDA-7 protein physically interacts with PKR. Transduction of PKR+/+ and PKR-/-
      transformed MEFs with Ad-mda7 demonstrated phosphorylated MDA-7 and PKR proteins
      in the lysates of PKR+/+ but not PKR-/- cells. These findings identify the first
      binding partner for MDA-7 and suggest that direct interaction between PKR and MDA
      7 may be important for PKR activation and apoptosis induction, possibly through
      MDA-7 phosphorylation or activation of other downstream targets.

PMID- 15851011
TI  - mda-7/IL24 kills pancreatic cancer cells by inhibition of the Wnt/PI3K signaling
      pathways: identification of IL-20 receptor-mediated bystander activity against
      pancreatic cancer.
AB  - The melanoma differentiation-associated gene (mda-7; approved gene symbol IL24)
      is a tumor suppressor gene whose protein expression in normal cells is restricted
      to the immune system and to melanocytes. Recent studies have shown that mda-7
      gene transfer inhibits cell growth and induces apoptosis in melanoma, lung
      cancer, breast cancer, and other tumor types through activation of various
      intracellular signaling pathways. In the current study, we demonstrate that Ad
      mda7 transduction of human pancreatic cancer cells results in G2/M cell cycle
      arrest and cell killing. Cytotoxicity is mediated via apoptosis in a time- and
      dose-dependent manner. Tumor cell killing correlates with regulation of proteins
      involved in the Wnt and PI3K pathways: beta-catenin, APC, GSK-3, JNK, and PTEN.
      Additionally, we identify bystander cell killing activated by exposure of
      pancreatic tumor cells to secreted human MDA-7 protein. In pancreatic tumor
      cells, exogenous MDA-7 protein activates STAT3 and kills cells via engagement of
      IL-20 receptors. The specificity of bystander killing is demonstrated using
      neutralizing anti-MDA-7 antibodies and anti-receptor antibodies, which inhibit
      the apoptotic effects. In sum, we show that Ad-mda7 is able to induce growth
      inhibition and apoptosis in pancreatic cancer cells via inhibition of the
      Wnt/PI3K pathways and identify a novel bystander mechanism of MDA-7 killing in
      pancreatic cancer that functions via IL-20 receptors.

PMID- 15851012
TI  - AAV-mediated expression of galactocerebrosidase in brain results in attenuated
      symptoms and extended life span in murine models of globoid cell leukodystrophy.
AB  - Globoid cell leukodystrophy (GLD) or Krabbe disease is a neurodegenerative
      disorder caused by a deficiency of galactocerebrosidase (GALC) activity. GALC is
      required for the lysosomal degradation of galactosylceramide, psychosine, and
      possibly other galactolipids. This process is extremely important during active
      myelination. In the absence of functional GALC, psychosine accumulates, resulting
      in the apoptotic death of myelin-producing cells. While most patients are infants
      who do not survive beyond 2 years of age, some older patients are also diagnosed.
      Hematopoietic stem cell transplantation has proven to have a positive effect on
      the course of some patients with late-onset Krabbe disease. Murine models of this
      disease provide an excellent opportunity to evaluate therapeutic alternatives
      including gene therapy. In this study we used serotype 1 AAV to express mouse
      GALC under the control of the human cytomegalovirus promoter. Direct
      administration of these viral particles into the brains of neonatal mice with GLD
      resulted in sustained expression of GALC activity, improved myelination,
      attenuated symptoms, and prolonged life span. While this treatment also resulted
      in significant pathological improvements, the treated mice died with symptoms
      similar to those of the untreated mice. Additional initiatives may be required to
      prevent the onset of disease and reverse the course of the disease in animal
      models and human patients.

PMID- 15851013
TI  - Restoration of aspartoacylase activity in CNS neurons does not ameliorate motor
      deficits and demyelination in a model of Canavan disease.
AB  - Canavan disease is an early onset leukodystrophy associated with psychomotor
      retardation, seizures, and premature death. This disorder is caused by mutations
      in the gene encoding the enzyme aspartoacylase (ASPA). Normally, ASPA is enriched
      in oligodendrocytes and ASPA deficiency results in elevated levels of its
      substrate molecule, N-acetylaspartate (NAA), brain edema, and dysmyelination.
      Using adeno-associated virus, we permanently expressed ASPA in CNS neurons of the
      tremor rat, a genetic model of Canavan disease, and examined the efficacy of the
      treatment by monitoring NAA metabolism, myelination, motor behavior, and
      seizures. Assessment of ASPA protein and enzyme activity in whole brain
      hemispheres showed restoration to normal levels as long as 6 months after
      treatment. This finding correlated with a reduction of NAA levels, along with a
      rescue of the seizure phenotype. However, gross brain pathology, such as dilated
      ventricles and spongiform vacuolization, was unchanged. Moreover, hypomyelination
      and motor deficits were not resolved by ASPA gene transfer. Our data suggest that
      NAA-mediated neuronal hyperexcitation but not oligodendrocyte dysfunction can be
      compensated for by neuronal ASPA expression.

PMID- 15851014
TI  - AAV vector-mediated correction of brain pathology in a mouse model of Niemann
      Pick A disease.
AB  - Niemann-Pick A disease (NPA) is a fatal lysosomal storage disorder caused by a
      deficiency in acid sphingomyelinase (ASM) activity. The lack of functional ASM
      results in cellular accumulation of sphingomyelin and cholesterol within
      distended lysosomes throughout the brain. In this study, we investigated the
      potential of AAV-mediated expression of ASM to correct the brain pathology in an
      ASM knockout (ASMKO) mouse model of NPA. An AAV serotype 2 vector encoding human
      ASM (AAV2-hASM) was injected directly into the adult ASMKO hippocampus of one
      hemisphere. This resulted in expression of human ASM in all major cell layers of
      the ipsilateral hippocampus for at least 15 weeks postinjection. Transduced cells
      were also present in the entorhinal cortex, medial septum, and contralateral
      hippocampus in a pattern consistent with retrograde axonal transport of AAV2.
      There was a substantial reduction of distended lysosomes and an almost complete
      reversal of cholesterol accumulation in all areas of the brain that were targeted
      by AAV2-hASM. These findings show that the ASMKO brain is responsive to ASM
      replacement and that retrograde transport of AAV2 functions as a platform for
      widespread gene delivery and reversal of pathology in affected brain.

PMID- 15851015
TI  - Efficient Tet-dependent expression of human factor IX in vivo by a new self
      regulating lentiviral vector.
AB  - Regulation of gene expression represents a long-sought goal of gene therapy.
      However, most viral vectors pose constraints on the incorporation of drug
      dependent transcriptional regulatory systems. Here, by optimizing the design of
      self-regulating lentiviral vectors based on the tetracycline system, we have been
      able to overcome the limitations of previously reported constructs and to reach
      both robust expression and efficient regulation from a single vector. The
      improved performance allows us to report for the first time effective long-term
      in vivo regulation of a human clotting Factor IX (hF.IX) transgene upon systemic
      administration of a single vector to SCID mice. We showed that hF.IX expression
      in the plasma could be expressed to therapeutically significant concentrations,
      adjusted to different set levels by varying the tetracycline dose, rapidly turned
      off and on, and completely recovered after each treatment cycle. The new vector
      design was versatile, as it successfully incorporated a tissue-specific promoter
      that selectively targeted regulated expression to hepatocytes. Robust transgene
      expression in the systemic circulation coupled to the ability to switch off and
      even adjust the expression level may open the way to safer gene-based delivery of
      therapeutics.

PMID- 15851016
TI  - Neonatal gene therapy of MPS I mice by intravenous injection of a lentiviral
      vector.
AB  - Mucopolysaccharidosis type I (MPS I) is a lysosomal glycosaminoglycan (GAG)
      storage disorder caused by deficiency of alpha-l-iduronidase (IDUA). In this
      study, we evaluated the potential to perform gene therapy for MPS I by direct in
      vivo injection of a lentiviral vector, using an IDUA gene knockout murine model.
      We compared the efficacy in newborn versus young adult MPS I mice of a single
      intravenous injection of the lentiviral vector. The extent of transduction was
      dose-dependent, with the liver receiving the highest level of vector, but other
      somatic organs reaching almost the same level. The phenotypic manifestations of
      disease were partially improved in the mice treated as young adults, but were
      nearly normalized at every end-point measured in the mice treated as neonates. In
      the neonatally treated mice, the expressed IDUA activity resulted in decreased
      GAG storage, prevention of skeletal abnormalities, a more normal gross
      appearance, and improved survival. Most strikingly, significant levels of IDUA
      enzyme were produced in the brain of mice treated as neonates, with transduction
      of neurons at high levels. The sustained expression of enzymatically active IDUA
      in multiple organs had a significant beneficial effect on the phenotypic
      abnormalities of MPS I, which may be translated to clinical gene therapy of
      patients with Hurler disease.

PMID- 15851017
TI  - Immunolipoplexes: an efficient, nonviral alternative for transfection of human
      dendritic cells with potential for clinical vaccination.
AB  - Genetic manipulation of dendritic cells (DCs) is important in the context of
      using either mature DCs to immunize patients or immature DCs to induce tolerance.
      Here, we describe a novel method of transfecting monocyte-derived human DCs using
      immunolipoplexes containing anti-CD71 or anti-CD205 monoclonal Abs. This results
      in up to 20% transfection, which can be increased to 20-30% if the
      immunolipoplexes are used to transfect CD14+ monocytes prior to differentiation
      into DCs. Transfected DCs can be substantially enriched using a drug-selection
      protocol during differentiation. Unlike adenoviral transduction, this nonviral
      transfection does not alter the expression of costimulatory molecules or the
      production of proinflammatory cytokines by DCs. In addition, DC function is
      unaltered, as assessed by mixed lymphocyte reactions. To test the feasibility of
      the immunolipoplexes and selection protocol for therapeutic intervention, we
      transfected DCs with the immunomodulatory enzyme indoleamine 2,3-dioxygenase
      (IDO). Allogeneic T cells exposed to IDO-expressing DCs did not proliferate,
      secreted more IL-10 and less Th1 and Th2 cytokines, and had a higher amount of
      apoptosis than T cells incubated with control DCs. Furthermore the remaining T
      cells were rendered anergic to further stimulation by allogeneic DC. These
      immunolipoplexes, which can be easily and rapidly assembled, have potential for
      clinical immunization, in particular for tolerance induction protocols.

PMID- 15851018
TI  - Nonbilayer phase of lipoplex-membrane mixture determines endosomal escape of
      genetic cargo and transfection efficiency.
AB  - Cationic lipids are widely used for gene delivery, and inclusion of
      dioleoylphosphatidylethanolamine (DOPE) as a helper lipid in cationic lipid-DNA
      formulations often promotes transfection efficacy. To investigate the
      significance of DOPE's preference to adopt a hexagonal phase in the mechanism of
      transfection, the properties and transfection efficiencies of SAINT-2/DOPE
      lipoplexes were compared to those of lipoplexes containing lamellar-phase-forming
      dipalmitoylphosphatidylethanolamine (DPPE). After interaction with anionic
      vesicles, to simulate lipoplex-endosomal membrane interaction, SAINT-2/DOPE
      lipoplexes show a perfect hexagonal phase, whereas SAINT-2/DPPE lipoplexes form a
      mixed lamellar-hexagonal phase. The transition to the hexagonal phase is crucial
      for dissociation of DNA or oligonucleotides (ODN) from the lipoplexes. However,
      while the efficiencies of nucleic acid release from either complex were similar,
      SAINT-2/DOPE lipoplexes displayed a two- to threefold higher transfection
      efficiency or nuclear ODN delivery. Interestingly, rupture of endosomes following
      a cellular incubation with ODN-containing SAINT-2/DPPE complexes dramatically
      improved nuclear ODN delivery to a level that was similar to that observed for
      SAINT-2/DOPE complexes. Our data demonstrate that although hexagonal phase
      formation in lipoplexes is a prerequisite for nucleic acid release from the
      complex, it appears highly critical for accomplishing efficient translocation of
      nucleic acids across the endosomal membrane into the cytosol for transport to the
      nucleus.

PMID- 15851019
TI  - Amplification of RNAi--targeting HLA mRNAs.
AB  - Posttranscriptional suppression of gene expression can be achieved by
      introduction of sequence-specific small interfering (si) RNA duplexes and by de
      novo intracellular synthesis of short sequence-specific double-stranded RNAs.
      However, achieving desired levels of knockdown is a barrier to successful
      analytic and therapeutic application. We demonstrate that increasing expression
      of introduced short hairpin RNA (shRNA) can markedly enhance RNA interference
      (RNAi) and that this approach can be used to achieve maximal target down
      regulation, when the choice of optimal siRNA-binding sites is restricted or when
      multiple genes are simultaneously targeted and the amount of siRNA is limiting. A
      dose-dependent RNAi effect was accomplished by placing copies of shRNA under
      control of the Pol III U6 small nuclear RNA promoter in tandem in a DNA vector.
      Using this system, we achieved simultaneous down-regulation of expression of
      classical human leukocyte antigen (HLA) class I genes in cultured and primary
      human T cells, which might be applied to help circumvent T-cell-mediated
      rejection of immunogenic and/or HLA-disparate allografts.

PMID- 15851020
TI  - From microbes to prions the final proof of the prion hypothesis.
AB  - Much like the "microbe hypothesis" put forth over 150 years ago, the "prion
      hypothesis" can be definitely proven only if a prion disease is engendered in a
      natural host from an infectious prion produced in vitro. In this issue of Cell,
      come very close to accomplishing this goal by producing a prion disease in a
      natural host from a prion entirely generated in vitro using a PCR-like
      amplification system.

PMID- 15851021
TI  - Two birds with one stone--dealing with nuclear transport and spindle assembly.
AB  - Spindle assembly and nuclear transport both utilize the same simple device: Ran
      GTP-sensitive interaction of importin beta and its cargo proteins. In this issue
      of Cell, report that one of these cargos required for spindle assembly turns out
      to be Rae1, previously known as an mRNA export protein. This study reveals the
      importance of RNAs in spindle structure.

PMID- 15851022
TI  - C2 can do it, too.
AB  - In this issue of Cell, report that the C2 domain of the serine/threonine protein
      kinase Cdelta is a phosphotyrosine binding domain and present the crystal
      structure of this C2 domain bound to a peptide containing phosphotyrosine. Prior
      to this work, C2 domains were thought to bind only to phospholipids or to
      unphosphorylated proteins, and the SH2 and PTB domains were the only signaling
      domains known to recognize phosphotyrosine. This new role for the C2 domain links
      phosphotyrosine recognition directly to serine/threonine kinase activity and
      reveals an unexpected mechanism for crosstalk between distinct signaling
      pathways.

PMID- 15851023
TI  - The complex cartography of stem cell commitment.
AB  - In this issue of Cell, a study by Adolfsson and coworkers (Adolfsson et al.,
      2005) provides insight into the early lineage commitment events of multipotent
      hematopoietic stem cells (HSCs). These studies demonstrate the importance of the
      Flt3 receptor tyrosine kinase as the earliest marker of hematopoietic cell fate
      commitment in that erythrocyte and megakaryocyte potentials are lost first as
      HSCs differentiate to lymphocyte progenitors.

PMID- 15851024
TI  - Chemicals call bacteria, and a new membrane protein machine answers.
AB  - A major challenge in biology is the discovery of the processes controlled by the
      roughly one-third of genes with no known function. One approach being explored to
      address this problem is the use of small molecules in conjunction with genetics
      chemical genetics. A short review of this field is provided as an introduction to
      a series of papers in this issue of Cell in which a new type of chemical genetics
      revealed the function of a new outer membrane protein complex in bacteria.

PMID- 15851025
TI  - hDOT1L links histone methylation to leukemogenesis.
AB  - Epigenetic modifications play an important role in human cancer. One such
      modification, histone methylation, contributes to human cancer through
      deregulation of cancer-relevant genes. The yeast Dot1 and its human counterpart,
      hDOT1L, methylate lysine 79 located within the globular domain of histone H3.
      Here we report that hDOT1L interacts with AF10, an MLL (mixed lineage leukemia)
      fusion partner involved in acute myeloid leukemia, through the OM-LZ region of
      AF10 required for MLL-AF10-mediated leukemogenesis. We demonstrate that direct
      fusion of hDOT1L to MLL results in leukemic transformation in an hDOT1L
      methyltransferase activity-dependent manner. Transformation by MLL-hDOT1L and MLL
      AF10 results in upregulation of a number of leukemia-relevant genes, such as
      Hoxa9, concomitant with hypermethylation of H3-K79. Our studies thus establish
      that mistargeting of hDOT1L to Hoxa9 plays an important role in MLL-AF10-mediated
      leukemogenesis and suggests that the enzymatic activity of hDOT1L may provide a
      potential target for therapeutic intervention.

PMID- 15851026
TI  - Phosphorylation and functional inactivation of TSC2 by Erk implications for
      tuberous sclerosis and cancer pathogenesis.
AB  - Tuberous sclerosis (TSC) is a tumor syndrome caused by mutation in TSC1 or TSC2
      genes. TSC tumorigenesis is not always accompanied by loss of heterozygosity
      (LOH). Recently, extracellular signal-regulated kinase (Erk) has been found
      activated in TSC lesions lacking TSC1 or TSC2 LOH. Here, we show that Erk may
      play a critical role in TSC progression through posttranslational inactivation of
      TSC2. Erk-dependent phosphorylation leads to TSC1-TSC2 dissociation and markedly
      impairs TSC2 ability to inhibit mTOR signaling, cell proliferation, and oncogenic
      transformation. Importantly, expression of an Erk nonphosphorylatable TSC2 mutant
      in TSC2+/- tumor cells where Erk is constitutively activated blocks
      tumorigenecity in vivo, while wild-type TSC2 is ineffective. Our findings
      position the Ras/MAPK pathway upstream of the TSC complex and suggest that Erk
      may modulate mTOR signaling and contribute to disease progression through
      phosphorylation and inactivation of TSC2.

PMID- 15851027
TI  - In vitro generation of infectious scrapie prions.
AB  - Prions are unconventional infectious agents responsible for transmissible
      spongiform encephalopathy (TSE) diseases. They are thought to be composed
      exclusively of the protease-resistant prion protein (PrPres) that replicates in
      the body by inducing the misfolding of the cellular prion protein (PrPC).
      Although compelling evidence supports this hypothesis, generation of infectious
      prion particles in vitro has not been convincingly demonstrated. Here we show
      that PrPC --> PrPres conversion can be mimicked in vitro by cyclic amplification
      of protein misfolding, resulting in indefinite amplification of PrPres. The in
      vitro-generated forms of PrPres share similar biochemical and structural
      properties with PrPres derived from sick brains. Inoculation of wild-type
      hamsters with in vitro-produced PrPres led to a scrapie disease identical to the
      illness produced by brain infectious material. These findings demonstrate that
      prions can be generated in vitro and provide strong evidence in support of the
      protein-only hypothesis of prion transmission.

PMID- 15851028
TI  - microRNA-directed phasing during trans-acting siRNA biogenesis in plants.
AB  - Plants and animals use small RNAs (microRNAs [miRNAs] and siRNAs) as guides for
      posttranscriptional and epigenetic regulation. In plants, miRNAs and trans-acting
      (ta) siRNAs form through distinct biogenesis pathways, although they both
      interact with target transcripts and guide cleavage. An integrated approach to
      identify targets of Arabidopsis thaliana miRNAs and ta-siRNAs revealed several
      new classes of small RNA-regulated genes, including conventional genes such as
      Argonaute2 and an E2-ubiquitin conjugating enzyme. Surprisingly, five ta-siRNA
      generating transcripts were identified as targets of miR173 or miR390. Rather
      than functioning as negative regulators, miR173- and miR390-guided cleavage was
      shown to set the 21-nucleotide phase for ta-siRNA precursor processing. These
      data support a model in which miRNA-guided formation of a 5' or 3' terminus
      within pre-ta-siRNA transcripts, followed by RDR6-dependent formation of dsRNA
      and Dicer-like processing, yields phased ta-siRNAs that negatively regulate other
      genes.

PMID- 15851029
TI  - A Rae1-containing ribonucleoprotein complex is required for mitotic spindle
      assembly.
AB  - Centrosome-independent microtubule polymerization around chromosomes has been
      shown to require a local gradient of RanGTP, which discharges mitotic cargoes
      from the nuclear import receptor importin beta. Here, we have used an activity
      based assay in Xenopus egg extracts to purify the mRNA export protein Rae1 as a
      spindle assembly factor regulated by this pathway. Rae1 is a microtubule
      associated protein that binds directly to importin beta. Depletion of Rae1 from
      extracts or cells severely inhibits mitotic spindle assembly. A purified Rae1
      complex stabilizes microtubules in egg extracts in a RanGTP/importin beta
      regulated manner. Interestingly, Rae1 exists in a large ribonucleoprotein
      complex, which requires RNA for its activity to control microtubule dynamics in
      vitro. Furthermore, we provide evidence that RNA associates with the mitotic
      spindle and that it plays a direct, translation-independent role in spindle
      assembly. Our studies reveal an unexpected function for RNA in spindle
      morphogenesis.

PMID- 15851030
TI  - Identification of a multicomponent complex required for outer membrane biogenesis
      in Escherichia coli.
AB  - Gram-negative bacteria have an outer membrane (OM) that functions as a barrier to
      protect the cell from toxic compounds such as antibiotics and detergents. The OM
      is a highly asymmetric bilayer composed of phospholipids, glycolipids, and
      proteins. Assembly of this essential organelle occurs outside the cytoplasm in an
      environment that lacks obvious energy sources such as ATP, and the mechanisms
      involved are poorly understood. We describe the identification of a multiprotein
      complex required for the assembly of proteins in the OM of Escherichia coli. We
      also demonstrate genetic interactions between genes encoding components of this
      protein assembly complex and imp, which encodes a protein involved in the
      assembly of lipopolysaccharides (LPS) in the OM. These genetic interactions
      suggest a role for YfgL, one of the lipoprotein components of the protein
      assembly complex, in a homeostatic control mechanism that coordinates the overall
      OM assembly process.

PMID- 15851031
TI  - Structural basis of pore formation by the bacterial toxin pneumolysin.
AB  - The bacterial toxin pneumolysin is released as a soluble monomer that kills
      target cells by assembling into large oligomeric rings and forming pores in
      cholesterol-containing membranes. Using cryo-EM and image processing, we have
      determined the structures of membrane-surface bound (prepore) and inserted-pore
      oligomer forms, providing a direct observation of the conformational transition
      into the pore form of a cholesterol-dependent cytolysin. In the pore structure,
      the domains of the monomer separate and double over into an arch, forming a wall
      sealing the bilayer around the pore. This transformation is accomplished by
      substantial refolding of two of the four protein domains along with deformation
      of the membrane. Extension of protein density into the bilayer supports earlier
      predictions that the protein inserts beta hairpins into the membrane. With an
      oligomer size of up to 44 subunits in the pore, this assembly creates a
      transmembrane channel 260 A in diameter lined by 176 beta strands.

PMID- 15851032
TI  - Structures of MLSBK antibiotics bound to mutated large ribosomal subunits provide
      a structural explanation for resistance.
AB  - Crystal structures of H. marismortui large ribosomal subunits containing the
      mutation G2099A (A2058 in E. coli) with erythromycin, azithromycin, clindamycin,
      virginiamycin S, and telithromycin bound explain why eubacterial ribosomes
      containing the mutation A2058G are resistant to them. Azithromycin binds almost
      identically to both G2099A and wild-type subunits, but the erythromycin affinity
      increases by more than 10(4)-fold, implying that desolvation of the N2 of G2099
      accounts for the low wild-type affinity for macrolides. All macrolides bind
      similarly to the H. marismortui subunit, but their binding differs significantly
      from what has been reported in the D. radioidurans subunit. The synergy in the
      binding of streptogramins A and B appears to result from a reorientation of the
      base of A2103 (A2062, E. coli) that stacks between them. The structure of large
      subunit containing a three residue deletion mutant of L22 shows a change in the
      L22 structure and exit tunnel shape that illuminates its macrolide resistance
      phenotype.

PMID- 15851033
TI  - The C2 domain of PKCdelta is a phosphotyrosine binding domain.
AB  - In eukaryotic cells, the SH2 and PTB domains mediate protein-protein interactions
      by recognizing phosphotyrosine residues on target proteins. Here we make the
      unexpected finding that the C2 domain of PKCdelta directly binds to
      phosphotyrosine peptides in a sequence-specific manner. We provide evidence that
      this domain mediates PKCdelta interaction with a Src binding glycoprotein, CDCP1.
      The crystal structure of the PKCdelta C2 domain in complex with an optimal
      phosphopeptide reveals a new mode of phosphotyrosine binding in which the
      phosphotyrosine moiety forms a ring-stacking interaction with a histidine residue
      of the C2 domain. This is also the first example of a protein Ser/Thr kinase
      containing a domain that binds phosphotyrosine.

PMID- 15851034
TI  - The strength of receptor signaling is centrally controlled through a cooperative
      loop between Ca2+ and an oxidant signal.
AB  - Activation of cell-surface receptors stimulates generation of intracellular
      signals that, in turn, direct the cellular response. However, mechanisms that
      ensure combinatorial control of these signaling events are not well understood.
      We show here that the Ca2+ and reactive oxygen intermediates generated upon BCR
      activation rapidly engage in a cooperative interaction that acts in a feedback
      manner to amplify the early signal generated. This cooperativity acts by
      regulating the concentration of the oxidant produced. The latter exerts its
      influence through a pulsed inactivation of receptor-coupled phosphatases, where
      the amplitude of this pulse is determined by oxidant concentration. The extent of
      phosphatase inhibition, in turn, dictates what proportion of receptor-proximal
      kinases are activated and, as a result, the net strength of the initial signal.
      It is the strength of this initial signal that finally determines the eventual
      duration of BCR signaling and the rate of its transmission through downstream
      pathways.

PMID- 15851035
TI  - Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic
      potential a revised road map for adult blood lineage commitment.
AB  - All blood cell lineages derive from a common hematopoietic stem cell (HSC). The
      current model implicates that the first lineage commitment step of adult
      pluripotent HSCs results in a strict separation into common lymphoid and common
      myeloid precursors. We present evidence for a population of cells which, although
      sustaining a high proliferative and combined lympho-myeloid differentiation
      potential, have lost the ability to adopt erythroid and megakaryocyte lineage
      fates. Cells in the Lin-Sca-1+c-kit+ HSC compartment coexpressing high levels of
      the tyrosine kinase receptor Flt3 sustain granulocyte, monocyte, and B and T cell
      potentials but in contrast to Lin-Sca-1+c-kit+Flt3- HSCs fail to produce
      significant erythroid and megakaryocytic progeny. This distinct lineage
      restriction site is accompanied by downregulation of genes for regulators of
      erythroid and megakaryocyte development. In agreement with representing a
      lymphoid primed progenitor, Lin-Sca-1+c-kit+CD34+Flt3+ cells display upregulated
      IL-7 receptor gene expression. Based on these observations, we propose a revised
      road map for adult blood lineage development.

PMID- 15851036
TI  - Chemical conditionality: a genetic strategy to probe organelle assembly.
AB  - The assembly of the Escherichia coli outer membrane (OM) is poorly understood.
      Although insight into fundamental cellular processes is often obtained from
      studying mutants, OM-defective mutants have not been very informative because
      they generally have nonspecific permeability defects. Here we show that toxic
      small molecules can be used in selections employing strains with permeability
      defects to create particular chemical conditions that demand specific suppressor
      mutations. Suppressor phenotypes are correlated with the physical properties of
      the small molecules, but the mutations are not in their target genes. Instead,
      mutations allow survival by partially restoring membrane impermeability. Using
      "chemical conditionality," we identified mutations in yfgL, and, here and in the
      accompanying paper by Wu et al. published in this issue of Cell (Wu et al.,
      2005), we show that YfgL is part of a multiprotein complex involved in the
      assembly of OM beta barrel proteins. We posit that panels of toxic small
      molecules will be useful for generating chemical conditionalities that enable
      identification of genes required for organelle assembly in other organisms.

PMID- 15851037
TI  - Clinical Radiology and the web: branching out and linking in.

PMID- 15851038
TI  - The scope of educational resources for radiologists on the internet.
AB  - The quantity of radiological educational resources available via the internet is
      enormous and is constantly increasing. The quality is variable, and much time can
      be wasted trying to find what is required. Web-based learning is highly
      attractive as it is widely available, cheap, accessible at any time and
      frequently updated (in contrast to conventional study materials). We present an
      introduction to the scope and diversity of educational websites in radiology.
      Effective evaluation of web-based material is essential to maximize the benefit
      to the user: a suitable method of evaluating radiological educational websites is
      described.

PMID- 15851039
TI  - Cardiothoracic radiology.
AB  - A wealth of cardiothoracic websites exist on the internet. What follows is a list
      of the higher quality resources currently available which should save you time
      searching them out for yourself. Many of the sites listed cater for
      undergraduates and trainee or non-specialist radiologists, nevertheless these may
      also be of interest to specialists in thoracic radiology, particularly for use in
      teaching. Hyperlinks are available in the electronic version of this article and
      were all active at the time of going to press (April 2005).

PMID- 15851040
TI  - The imaging of lumbar spondylolisthesis.
AB  - Lumbar spondylolisthesis is a common finding on plain radiographs. The condition
      has a variety of causes which can be differentiated on the basis of imaging
      findings. As the treatment is dependent upon the type of spondylolisthesis, it is
      important for the radiologist to be aware of these features. We present a
      pictorial review of the imaging features of lumbar spondylolisthesis and explain
      the differentiating points between different groups of this disorder. The
      relative merits of the different imaging techniques in assessing lumbar
      spondylolisthesis are discussed.

PMID- 15851041
TI  - Recurrence of squamous cell carcinoma of the oesophagus after curative surgery:
      rates and patterns on imaging studies correlated with tumour location and
      pathological stage.
AB  - Many factors have been related to recurrence after resection of squamous cell
      carcinoma of the oesophagus. These include age, gender, location and local stage
      of tumours, cell differentiation, lymph node metastasis and vascular involvement.
      The recurrence rates of squamous cell carcinoma after curative surgery are high
      (34-79%). Tumour recurrence is categorized as locoregional or distant. Lymph node
      recurrence and haematogenous metastasis to solid organs (commonly to the lung)
      are the usual patterns of recurrence. Awareness of recurrence patterns,
      particularly on imaging studies, is essential for the diagnosis of recurrent
      tumours on follow-up examinations.

PMID- 15851042
TI  - National audit of the sensitivity of double-contrast barium enema for colorectal
      carcinoma, using control charts.

PMID- 15851043
TI  - National audit of the sensitivity of double-contrast barium enema for colorectal
      carcinoma, using control charts For the Royal College of Radiologists Clinical
      Radiology Audit Sub-Committee.
AB  - AIM: To audit the sensitivity of double-contrast barium enema (DCBE) for
      colorectal carcinoma, as currently practised in UK departments of radiology.
      METHODS: As part of its programme of national audits, the Royal College of
      Radiologists Clinical Radiology Audit Sub-Committee undertook a retrospective
      audit of the sensitivity of DCBE for colorectal carcinoma during 2002. The
      following targets were set: demonstration of a lesion > or =95%; correct
      identification as a carcinoma > or =90%. RESULTS: Across the UK, 131 departments
      took part in the audit, involving 5454 examinations. The mean demonstration rate
      was 92.9% and the diagnosis rate was 85.9%, slightly below the targets set. The
      equivocal rate (lesion demonstrated, but not defined as malignant) was 6.9%, the
      perception failure rate was 2.8% and the technical failure rate was 4.4%. Control
      chart methodology was used to analyze the data and to identify any departments
      whose performance was consistent with special-cause variation. CONCLUSION: When
      compared with the diagnosis rate (84.6%) and demonstration rate (92.7%) reported
      in the Wessex Audit 1995, [Thomas RD, Fairhurst JJ, Frost RA. Wessex regional
      audit: barium enema in colo-rectal carcinoma. Clin Radiol 1995;50:647-50.] a
      similar level of performance was observed in the NHS today, implying that the
      basic process for undertaking and reporting DCBE has remained relatively
      unchanged over the last few years. Improvement in the future will require
      fundamental changes to the process of reporting DCBE, in order to minimize the
      perception failure rate and accurately to describe lesions, so reducing the
      equivocal rate. Control-chart methodology has a useful role in identifying
      strategies to deliver continual improvement.

PMID- 15851044
TI  - Detection and evaluation of intracranial aneurysms with 16-row multislice CT
      angiography.
AB  - AIM: The aim of this study was to assess the usefulness of 16-row multislice CT
      angiography (CTA) in evaluating intracranial aneurysms, by comparison with
      conventional digital subtraction angiography (DSA) and intraoperative findings.
      METHODS: A consecutive series of 57 patients, scheduled for DSA for suspected
      intracranial aneurysm, was prospectively recruited to have CTA. This was
      performed with a 16-detector row machine, detector interval 0.75 mm, 0.5
      rotation/s, table speed 10mm/rotation and reconstruction interval 0.40 mm. CTA
      studies were independently and randomly assessed by two neuroradiologists and a
      vascular neurosurgeon blinded to the DSA and surgical findings. Review of CTA was
      performed on workstations with an interactive 3D volume-rendered algorithm.
      RESULTS: DSA or intraoperative findings or both confirmed 53 aneurysms in 44
      patients. For both independent readers, sensitivity and specificity per aneurysm
      of DSA were 96.2% and 100%, respectively. Sensitivity and specificity of CTA were
      also 96.2% and 100%, respectively. Mean diameter of aneurysms was 6.3mm (range
      1.9 to 28.1 mm, SD 5.2 mm). For aneurysms of less than 3 mm, CTA had a
      sensitivity of 91.7% for each reader. Although the neurosurgeon would have been
      happy to proceed to surgery on the basis of CTA alone in all cases, he judged
      that DSA might have provided helpful additional anatomical information in 5
      patients. CONCLUSION: The diagnostic accuracy of 16-slice CTA is promising and
      appears equivalent to that of DSA for detection and evaluation of intracranial
      aneurysms. A strategy of using CTA as the primary imaging method, with DSA
      reserved for cases of uncertainty, appears to be practical and safe.

PMID- 15851045
TI  - Increasing the diagnosis of multifocal primary breast cancer by the use of
      bilateral whole-breast ultrasound.
AB  - AIM: The aim of this study was to evaluate the contribution of bilateral whole
      breast ultrasound (BBUS) to the diagnosis and management of women with newly
      diagnosed breast cancer. METHODS: Over a period of 6 months, 102 women presenting
      with breast cancer underwent BBUS. Data were collected on clinical findings,
      radiology, histology and surgical outcome. These women were compared with a
      control group of 124 women presenting over a similar 6-month period 1 year
      previously, who had undergone targeted breast ultrasound. RESULTS:
      Multicentric/multifocal tumours were demonstrated in 35 (34%) of the 102
      participants and in 18 (15%) of the 124 controls, a statistically significant
      difference (Fisher's exact test, p = 0.001). Multiple tumours were diagnosed
      preoperatively in 18% of the study population compared with 8% of the controls,
      and BBUS identified invasive multifocal/multicentric tumours in significantly
      more women in the study population (11 versus 1 control) (Fisher's exact test, p
      = 0.019). Contralateral cancer was diagnosed in 4 women in the study population
      and none in the control population (Fisher's exact test, p = 0.040). Surgical
      review showed that the surgical management changed significantly in 8% (95%
      confidence interval 4 to 14%) of cases in the study population following BBUS.
      The increase in the number of women undergoing benign biopsies in the study
      population (10 versus 5 controls) was not statistically significant (Fisher's
      exact test, p = 0.11). CONCLUSION: BBUS increased the preoperative diagnosis of
      multiple tumours in women presenting with primary breast cancer, resulting in a
      management change in 8% of cases.

PMID- 15851046
TI  - Preoperative staging of rectal cancer by MRI; results of a UK survey.
AB  - AIM: To determine current day-to-day practice of and access to preoperative MRI
      for patients with rectal cancer in the UK, with the aim of identifying
      constraining factors. MATERIALS AND METHODS: A questionnaire asking for details
      of rectal cancer workload, multidisciplinary team (MDT) practice, preoperative
      MRI, the use of alternative imaging methods where appropriate, and an assessment
      of local access to MRI, was mailed to 283 UK departments of radiology. Replies
      were received from 142 departments (50.2% response rate). These were collated and
      response frequencies were determined. RESULTS: According to their replies, 135
      (95%) of respondents always discussed rectal cancer cases within the context of
      an MDT, usually including a radiologist. Only 49% of respondents attempted to
      offer preoperative MRI to all rectal cancer patients, and 35% of respondents used
      MRI in less than 25% of cases. Of the 142 respondents, 73 (51%) felt their
      practice was currently constrained by lack of MR resources. The most frequently
      cited constraint was an available but over-subscribed MRI scanner. Limited
      radiology manpower was the next most frequently cited constraint. A significant
      minority stated that no MRI scanner was available. CONCLUSIONS: The MDT is a well
      established forum for the discussion of patients with rectal cancer, and a
      radiologist is usually involved. However, in the face of current guidelines, less
      than 50% of the units studied were able to offer preoperative MRI to all of their
      rectal cancer cases. Improved access to MRI and increased radiological manpower
      are necessary if current management guidelines are to be observed.

PMID- 15851047
TI  - Coagulation necrosis in malignant mediastinal nodes on endoscopic ultrasound: a
      new endosonographic sign.
AB  - AIMS: Endoscopic ultrasound (EUS) can be used to assess mediastinal lymph nodes,
      and EUS-guided transoesophageal fine needle aspiration (EUS-FNA) can provide a
      tissue diagnosis. Previous studies suggest that a uniformly hypoechoic
      echotexture is a feature of malignant nodes, and echogenic structures within
      nodes are due to the normal hilum. Ill-defined, non-shadowing echogenic areas
      within malignant lymph nodes have been termed coagulation necrosis (CN) on neck
      ultrasound. The purpose of this study is to determine whether CN can be detected
      on EUS and be used as a predictive sign for malignancy in mediastinal lymph
      nodes. METHODS: A total of 36 individuals who underwent EUS-FNA of mediastinal
      lymph nodes were initially included. A radiologist experienced in neck
      ultrasound, and blinded to the final diagnosis, reviewed hard-copy films for CN.
      Comparison was made with the EUS-FNA result and the final diagnosis. RESULTS:
      Four patients were excluded because their films were deemed inadequate for
      retrospective diagnosis. The remaining 32 patients were all included, and 11
      showed CN. Of the 11 cases, 10 had malignant cytology on EUS-FNA; and in the
      remaining case follow-up indicated a false-negative EUS-FNA. Of the 21 subjects
      with no CN, the final diagnosis was malignant in 12 and non-malignant in 9 cases.
      No participant with a final benign diagnosis had CN. CONCLUSION: Echogenic
      structures within mediastinal lymph nodes on EUS are not necessarily due to the
      normal hilum. Careful analysis of the intranodal echo pattern may reveal CN. CN
      can be used as a predictive sign of malignancy and EUS-FNA should be targeted
      towards these nodes.

PMID- 15851048
TI  - Human cervical lymphadenopathy: evaluation with in vivo 1H-MRS at 1.5 T.
AB  - AIM: To evaluate the feasibility of performing in vivo proton magnetic resonance
      spectroscopy ((1)H-MRS) of cervical lymph nodes, and the clinical usefulness of
      the technique in the characterization of cervical lymphadenopathy. MATERIALS AND
      METHODS: Cervical lymphadenopathy was examined in 20 individuals with malignant
      disease, i.e. 10 with squamous cell carcinoma (SCC), 6 with undifferentiated
      carcinoma (UDC) and 4 with non-Hodgkin's lymphoma (NHL). Cervical lymphadenopathy
      was also examined in 4 individuals with benign disease, i.e. 3 with tuberculosis
      (TB) and 1 with Castleman's disease. A point-resolved spectroscopic sequence with
      echo times (TE) of 136 and 272 ms and a time-domain spectral fitting procedure
      were used to estimate peak amplitude of choline (Cho), creatine (Cr) and
      unsuppressed water. Cho/Cr and Cho/water ratios were measured for each lesion.
      The mean ratio for each lesion group was obtained and results were compared
      statistically. RESULTS: At TE of 136 ms, spectra were interpretable in all 24
      cases and a Cr peak was identified with post-processing in 15 cases. The Cho/Cr
      and Cho/water ratios for NHL were 9.1 +/- 5.2 and 1.7 +/- 0.2 x 10(-3), for UDC
      were 4.4 +/- 0.9 and 1.2 +/- 0.4 x 10(-3), and for SCC were 2.1 +/- 0.6 and 0.5
      +/- 0.3 x 10(-3), respectively. Both Cho/Cr and Cho/water ratios for UDC were
      significantly higher than SCC (p = 0.002 and 0.026, respectively). At TE of 272
      ms, spectra were interpretable in 22 of 24 cases and a Cr peak was identified
      with post-processing in 11 cases. Cho/Cr and Cho/water ratios for NHL were 5.4
      and 4.6 +/- 1.4 x 10(-3), for UDC were 4.2 +/- 1.5 and 2.6 +/- 1.0 x 10(-3) and
      for SCC were 2.5 +/- 1.1 and 1.3 +/- 0.6 x 10(-3), respectively. The Cho/water
      ratio for UDC was significantly higher than for SCC (p = 0.04). The Cho/Cr ratio
      for UDC was also higher than for SCC, but this difference was not statistically
      significant (p = 0.07). Neither Cho nor Cr was detected in the 3 cases of TB.
      CONCLUSION: In vivo (1)H-MRS is a feasible technique for the evaluation of
      cervical lymph nodes and it offers potential as a clinical tool in the
      investigation of cervical lymphadenopathy. However, further studies with larger
      patient cohorts are needed to validate the findings of this initial report.

PMID- 15851049
TI  - The halo sign and peripancreatic fluid: useful CT signs of hypovolaemic shock
      complex in adults.
AB  - AIM: To report two new, useful computed tomography (CT) signs of the hypovolaemic
      shock complex (HSC) in adults admitted after blunt abdominal trauma: the halo
      sign (ring of fluid around a collapsed intra-hepatic inferior vena cava (IVC)),
      and peripancreatic retroperitoneal fluid. MATERIALS AND METHODS: CT images of 498
      consecutive patients admitted after blunt abdominal trauma were reviewed, of
      which 27 had CT signs of the HSC. The CT images of these 27 patients were
      analysed. A control group of 101 patients examined using CT for suspected blunt
      abdominal trauma who did not have the HSC were chosen for comparison. RESULTS:
      The most common features involved the vascular compartment: diminished IVC
      diameter n = 27 a positive halo sign n = 21 diminished anteroposterior diameter
      of the aorta n = 13 and abnormal vascular enhancement n = 10. Peripancreatic
      retroperitoneal fluid in the absence of pancreatic injury, pancreatitis or
      pancreatic disease was observed in eight patients. Hollow visceral abnormalities
      included: diffuse increased mucosal enhancement of both the small and large bowel
      n = 19 diffuse thickening of the small bowel wall n =11 and small bowel
      dilatation n = 7. Solid visceral abnormalities included both decreased and or
      increased enhancement. Several concomitant intra- and extra-abdominal injuries
      were also identified. CONCLUSION: In the setting of blunt abdominal trauma, early
      abdominal CT can show diffuse abnormalities due to the HSC, which occasionally
      may alert clinicians of unsuspected shock. Recognition of these signs as
      distinguished from injured viscera is important in order to avoid unnecessary
      laparotomy. Two new signs are described: the halo sign and peripancreatic
      retroperitoneal fluid.

PMID- 15851050
TI  - Retrograde or antegrade double-pigtail stent placement for malignant ureteric
      obstruction?
AB  - AIM: To determine the optimum approach for double-pigtail stent placement in
      malignant ureteric obstruction. PATIENTS AND METHODS: Retrograde stent placement
      was attempted in a consecutive series of patients presenting with malignant
      ureteric obstruction. If retrograde stent placement was unsuccessful,
      percutaneous nephrostomy was performed immediately followed by elective antegrade
      stent placement. Identical digital C-arm fluoroscopy for image-guidance and
      conditions for anaesthesia and analgesia were employed for both retrograde and
      antegrade procedures. Identical 8 Fr (20-26 cm) double-pigtail hydrophilic coated
      stents were used for each approach. RESULTS: Retrograde placement was attempted
      in 50 ureters in 30 patients {19 male, 11 female, average age 61.4 yr (range 29
      90 yr)} over a 24-month period. The success rate for retrograde ureteric stent
      placement was 50% (n = 25/50). Technical failures were due to failure to identify
      the ureteric orifice (n = 22), failure to cross the stricture (n = 1), failure to
      pass the stent (n = 1) and failure to pass a 4 Fr catheter (n = 1). Antegrade
      placement was attempted in 25 ureters with a success rate of 96% (n = 24/25).
      Failure in the one case was due to inability to cross an upper third stricture
      secondary to pyeloureteritis cystica. CONCLUSION: It is suggested that retrograde
      route should be the initial approach if imaging shows no involvement of ureteric
      orifice (UO), when nephrostomy is technically very difficult or in cases of
      solitary kidney. The antegrade route is preferred if imaging shows tumour
      occlusion of the UO or if there is a tight stricture very close to the uretero
      vesical junction (UVJ) making purchase within the ureter difficult for crossing
      the stricture.

PMID- 15851051
TI  - "Burnt out" varicella-zoster-virus encephalitis in an AIDS patient following
      treatment by highly active antiretroviral therapy.

PMID- 15851053
TI  - Awareness of 'Making the best use of a Department of Clinical Radiology' amongst
      physicians.

PMID- 15851054
TI  - The value of performing head CT in screening for cerebral metastases in patients
      with potentially resectable non-small cell lung cancer: experience from a UK
      cardiothoracic centre.

PMID- 15851056
TI  - Transcriptional consequences of autosomal trisomy: primary gene dosage with
      complex downstream effects.
AB  - Autosomal trisomy is a common cause of human miscarriage, malformations and
      learning disability. Primary gene-dosage effects have been confirmed by recent
      transcriptome analyses. The importance (or existence) of trans-acting effects on
      disomic genes remains, surprisingly, controversial. In this article, I propose a
      model of the main genetic mechanisms that are responsible for producing the
      transcriptional derangement associated with trisomy. This has implications for
      future study design.

PMID- 15851057
TI  - The contested role of uracil DNA glycosylase in immunoglobulin gene
      diversification.
AB  - Class switch recombination (CSR) and somatic hypermutation (SHM) of
      immunoglobulin (Ig) genes are initiated by the activation-induced cytosine
      deaminase AID. The resulting uracils in Ig genes were believed to be removed by
      the uracil glycosylase (UNG) and the resulting abasic sites treated in an error
      prone fashion, creating breaks in the Ig switch regions and mutations in the
      variable regions. A recent report suggests that UNG does not act as a glycosylase
      in CSR and SHM but rather has unknown activity subsequent to DNA breaks that were
      created by other mechanisms.

PMID- 15851058
TI  - Biased codon usage near intron-exon junctions: selection on splicing enhancers,
      splice-site recognition or something else?
AB  - Two groups recently argued that, in human genes, synonymous sites near intron
      exon junctions undergo selection for correct splicing. However, neither study
      controlled for the possibility of an underlying nucleotide bias at the ends of
      exons. In this article, we show that generalized A and T enrichment exists, which
      could be independent of splicing regulation. Evidence for selection between
      synonymous codons that are associated with splicing enhancers remains after
      controlling for this bias, whereas support for cryptic splice-site avoidance is
      diminished.

PMID- 15851059
TI  - Transcription attenuation: a highly conserved regulatory strategy used by
      bacteria.
AB  - We employed computational analyses to assess the conservation of sequence
      elements that are believed to be essential for the various transcription
      attenuation (termination) mechanisms that are used to regulate expression of
      families of orthologous genes in bacteria. We searched the upstream sequence of
      every predicted transcription unit for a transcription attenuator. These were
      then clustered by the orthology relationships of the nearby structural genes.
      Many gene families regulated by transcription attenuation were found to be
      adjacent to a regulatory region that had a binding site for a specific protein,
      tRNA or small metabolite. Using our methodology, we predict that at least 80
      different clusters of orthologous groups (COGs) are significantly regulated by
      transcription attenuation.

PMID- 15851060
TI  - Guanine-adenine bias: a general property of retroid viruses that is unrelated to
      host-induced hypermutation.
AB  - The recently discovered mammalian enzymes, APOBEC3G and 3F, induce guanine-to
      adenine hypermutation in retroviruses. However, the preference of adenine over
      guanine in retroviral codon usage is not correlated with the presence or absence
      of APOBEC3G or its viral inhibitor (Vif), and its pattern does not reflect the
      biochemical properties of APOBEC3G action. The guanine-adenine bias of
      retroviruses is thus probably not a result of host-induced mutational pressure,
      but rather reflects a general predisposition associated with reverse
      transcription.

PMID- 15851061
TI  - Conventional P-values fail to assure reproducibility for genetic association
      tests.

PMID- 15851063
TI  - Replication fork dynamics and dynamic mutations: the fork-shift model of repeat
      instability.
AB  - Gene-specific repeat instability is responsible for >36 human diseases. Active
      instability varies in a tissue-, developmental stage- and locus-specific manner
      and occurs in both proliferative and non-proliferative cells. In proliferative
      cells, DNA replication can contribute to repeat instability either by switching
      the direction of replication, which changes the repeat sequence that serves as
      the lagging-strand template (origin switching), or by shifting the location of
      the origin of replication without altering the replication direction (origin
      shifting). We propose that changes in the dynamics of replication-fork
      progression, or architecture, will alter the location of the repeat within the
      single-stranded lagging-strand template, thereby influencing instability (fork
      shifting). The fork-shift model, which does not require origin relocation, is
      influenced by cis-elements and trans-factors associated with driving and
      maintaining replication forks. The fork-shift model can explain some of the
      complex behaviours of repeat instability because it is dynamic and responsive to
      variations in epigenomic and locus activity.

PMID- 15851064
TI  - Maternal inheritance, sexual conflict and the maladapted male.
AB  - Females differ from males in transmitting not only nuclear genes but also
      cytoplasmic genetic elements (CGEs), including DNA in mitochondria, chloroplasts
      and microorganisms that are present in the cell. Until recently, evolutionary
      research has adopted a nucleocentric approach in which organelles have been
      viewed as subservient energy suppliers. In this article, we propose that a more
      equitable view of nuclear genes and organelle genomes will lead to a better
      understanding of the dynamics of sexual selection and the constraints on male
      adaptation. Maternal inheritance of CGEs intensifies sexually-antagonistic
      coevolution and provides a parsimonious explanation for the relatively high
      frequency in males of such apparently maladaptive traits as infertility,
      homosexuality and baldness.

PMID- 15851065
TI  - Waste not, want not--transcript excess in multicellular eukaryotes.
AB  - There is growing evidence that mammalian genomes produce thousands of transcripts
      that do not encode proteins, and this RNA class might even rival the complexity
      of mRNAs. There is no doubt that a number of these non-protein-coding RNAs have
      important regulatory functions in the cell. However, do all transcripts have a
      function or are many of them products of fortuitous transcription with no
      function? The second scenario is mirrored by numerous alternative-splicing events
      that lead to truncated proteins. Nevertheless, analogous to 'superfluous' genomic
      DNA, aberrant transcripts or processing products embody evolutionary potential
      and provide novel RNAs that natural selection can act on.

PMID- 15851066
TI  - Non-coding RNAs: hope or hype?
AB  - The past four years have seen an explosion in the number of detected RNA
      transcripts with no apparent protein-coding potential. This has led to
      speculation that non-protein-coding RNAs (ncRNAs) might be as important as
      proteins in the regulation of vital cellular functions. However, there has been
      significantly less progress in actually demonstrating the functions of these
      transcripts. In this article, we review the results of recent experiments that
      show that transcription of non-protein-coding RNA is far more widespread than was
      previously anticipated. Although some ncRNAs act as molecular switches that
      regulate gene expression, the function of many ncRNAs is unknown. New
      experimental and computational approaches are emerging that will help determine
      whether these newly identified transcription products are evidence of important
      new biochemical pathways or are merely 'junk' RNA generated by the cell as a by
      product of its functional activities.

PMID- 15851067
TI  - Sexual dimorphism in mammalian gene expression.
AB  - Males and females have obvious phenotypic differences; they also exhibit
      differences related to health, life span, cognitive abilities and have different
      responses to diseases such as anemia, coronary heart disease, hypertension and
      renal dysfunction. Although the anatomical, hormonal and chemical differences
      between the sexes are well known, there are few molecular descriptors for gender
      specific physiological traits and health risks. Recent studies using microarrays
      and other methods have made significant progress towards elucidating the
      molecular differences between mammalian sexes in a variety of tissues and towards
      identifying the transcription factors that regulate sex-biased gene expression.
      These findings are providing new insights into the molecular and genetic
      differences that dictate the different behaviors and physiologies of mammalian
      sexes.

PMID- 15851068
TI  - Therapy for intracerebral hemorrhage.

PMID- 15851069
TI  - Imaginem oblivionis: the prospects of neuroimaging for early detection of
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      characterised by the gradual onset of dementia. The pathological hallmarks of the
      disease are A beta amyloid plaques, neurofibrillary tangles, and reactive
      gliosis. Current diagnosis of AD is made by clinical, neuropsychologic, and
      neuroimaging assessments. Routine structural neuroimaging evaluation is based on
      non-specific features such as atrophy, a late feature in the progression of the
      disease, hence the crucial importance of developing new approaches for early and
      specific recognition at the prodromal stages of AD. Functional neuroimaging
      techniques such as positron emission tomography (PET) and single photon emission
      computed tomography (SPECT) could prove to be valuable in the differential
      diagnosis of AD, as well as in assessing prognosis. With the advent of new
      therapeutic strategies aimed at reducing the A beta amyloid burden in the brain,
      there is increasing interest in the development of PET and SPECT radioligands
      that will permit the assessment of A beta amyloid burden in vivo. From this, the
      prospect of specific preclinical diagnosis arises, possibly in conjunction with
      other related A beta biomarkers in plasma and CSF.

PMID- 15851070
TI  - Remembrance of things past: an inquiry into the fate of the Istanbul medical
      students who fought in the Gallipoli campaign.
AB  - During the Great War, university students, like all young men at the age of
      military service, were called up as part of the general conscription in the
      Ottoman Empire. According to a popular story, which is the subject of this study,
      all Darulfunun (today Istanbul University) students who took part in the
      Gallipoli campaign as volunteers in May, 1915, were annihilated in the May 19th
      attack. As all students of 1,915 were lost, the medical school was said to have
      had no graduates in 1921. This investigation was carried out, using material from
      the university and military archives, to identify the medical students who died
      on the Gallipoli battlefield, and to clarify their situation at that time. It was
      found that, as academic staff and students were distributed to the troops,
      education never commenced in 1915 and that the faculty building was closed for
      more than a year to serve as an inland war hospital. As all students were drafted
      into the army, there were no graduates in 1915. While it has been possible to
      identify eight physicians who died on the Gallipoli battlefield, no records were
      found concerning the medical students who were killed at Gallipoli.

PMID- 15851071
TI  - Clinical analysis of non-accidental head injury in infants.
AB  - We present the clinical features, radiological findings and outcome of infants
      with non-accidental head injury presenting to our department between 2001 and
      2003. There were 26 male and 13 female infants, aged between 7 days and 5 months.
      Presenting symptoms included seizures, vomiting, bulging fontanel, decreased
      level of consciousness, focal neurological signs, anemia and respiratory
      distress. We classified the patients into three groups: mild head injury (8
      patients), moderate head injury (11 patients) and severe head injury (20
      patients). Detailed history taking and thorough physical examination, did not
      reveal obvious injury or abuse (by the parents), other external visible injury or
      significant incidence of retinal bleeding. CT scan showed intracranial hemorrhage
      in all patients, most commonly including acute or acute on chronic subdural
      hematoma (SDH) and subarachnoid hemorrhage (SAH) in the parafalcine and tentorial
      regions and over the brain convexity, associated with focal or diffuse
      hypodensity of the parenchyma. Intracranial lesions were mostly bilateral (80%).
      These patients generally had a poor outcome; 31% died, 23% had a good outcome,
      and the remainder recovered with neurological impairment of varying types and
      degrees. After comprehensive assessment, we concluded that all the cases in our
      series were "non-accidental" head injuries. However, the absence of retinal
      bleeding, visible external injury and recognised abuse in our series differed
      from reports by other investigators. In our opinion these features are not
      absolute requirements in diagnosing "non-accidental" injury and detailed history
      taking, thorough clinical examination and radiological studies were the key
      indicators of the diagnosis.

PMID- 15851072
TI  - Somatotopic organization of the human periventricular gray matter.
AB  - The periventricular gray (PVG) matter is an established anatomical target for
      chronic deep brain stimulation (DBS) in the treatment of certain intractable pain
      syndromes. Data relating to the representation of pain and other somatosensory
      modalities within the PVG in humans are negligible. We examined the character and
      location of somatosensory responses elicited by electrical stimulation along the
      length of the PVG in a patient who underwent unilateral DBS for intractable
      nociceptive head pain. Consistent responses were obtained and indicated the
      presence of a somatotopic representation in this region. The contralateral lower
      limb was represented cranially, followed by the upper limb and trunk, with the
      face area located caudally, near the level of the superior colliculi. Bilateral
      representation was only observed in the forehead and scalp.

PMID- 15851073
TI  - Complete response of brain metastases to irinotecan-based chemotherapy.
AB  - Brain metastases occur in 15-20% of patients with cancer and are generally
      associated with an overall poor prognosis. Currently, radiotherapy and surgery
      are the mainstay of palliative therapy for patients with brain metastases, while
      the role of systemic chemotherapy remains uncertain. In this article, we report
      complete responses to irinotecan-based chemotherapy in three patients with brain
      metastases from parotid adenocarcinoma, esophageal adenocarcinoma and small cell
      lung cancer. Irinotecan-based chemotherapy may hold promise in treating patients
      with brain metastases. Further studies are warranted to confirm our observations.

PMID- 15851074
TI  - Primary spinal tumors in children.
AB  - Nine patients, 16 years of age or younger with primary spinal cord tumors,
      diagnosed between 1991 and 2003 at The Kaohsiung University Hospital, were
      reviewed retrospectively. There were 2 female and 7 male patients. Two tumors
      were located primarily in the cervical cord (1 meningioma, 1 neurofibroma), five
      were predominantly thoracic (1 lymphoma, 1 meningioma, 1 astrocytoma, 1
      fibrosarcoma and 1 osteoblastoma), one lumbar (ependymoma), and one sacral
      (Ewing's sarcoma). The most common clinical presentation was limb weakness (100%)
      followed by back pain (44.4%). All the patients underwent laminectomy for removal
      of their tumors. Five children with benign tumors improved postoperatively. At
      discharge, these 5 children could walk without assistance and have remained
      stable with long-term of follow-up. Radical surgery should be considered in
      benign primary spinal cord tumors. As would be expected, patients diagnosed and
      treated early and in whom a total resection was achieved had a better prognosis.

PMID- 15851075
TI  - Terminal myelocystocele.
AB  - Myelocystocele is a variety of occult spinal dysraphism that is characterized by
      a localized, cystic dilatation of the terminal part of the central canal that
      then herniates through a posterior spina bifida. We describe a series of eight
      cases of myelocystocele. The clinical and radiological features and treatment are
      discussed and the relevant literature reviewed.

PMID- 15851076
TI  - Cystic acoustic neuroma.
AB  - To define the clinical characteristics of cystic acoustic neuroma, we
      retrospectively analyzed 22 patients with cystic acoustic neuroma and reviewed
      the literature with regard to clinical manifestation, imaging features,
      diagnosis, surgical procedures and prognosis. An acoustic neuroma was defined as
      cystic according to the following criteria: the presence of hypodense/hypointense
      areas on CT or MRI, the identification of cystic elements at operation and
      histological verification. At the end of surgery, the facial nerve was
      anatomically intact in 86.4% of cystic acoustic neuromas. Complete removal of the
      tumor was achieved in 18 cases (81.8%). We conclude that patients with cystic
      acoustic neuroma need prompt surgery with special attention paid to the
      preservation of the facial nerve.

PMID- 15851077
TI  - Neuroendoscopic anatomy and surgery of the cerebellopontine angle.
AB  - To probe the feasibility and utility of neuroendoscopic inspection of the anatomy
      of the cerebellopontine angle (CPA) and of neuroendoscopic assisted
      microneurosurgery (NEAMN) for CPA lesions via a retrosigmoid approach, we used
      retrosigmoid NEAMN in 28 patients with CPA lesions. Prior to this, we undertook
      anatomical observation of bilateral CPA in two adult cadaver heads using the
      neuroendoscope. NEAMN tumour resection was performed in eight acoustic neuromas,
      one meningioma and 14 cholesteatomas and NEAMN vascular decompression was
      performed in five patients with trigeminal neuralgia. Both the neurovascular
      structures of the CPA and the ventral surface of the pons, as well as the clivus,
      can be inspected using the neuroendoscope through a retrosigmoid approach with a
      2-3 cm diameter bony opening. Complete excision of the tumour with preservation
      of the facial nerve was achieved in all eight acoustic neuromas. Likewise, total
      resection of the tumour was possible in the 14 cholesteatomas and one meningioma.
      Paroxysmal facial pain resolved after NEAMN vascular decompression in the five
      patients with trigeminal neuralgia. There were no postoperative complications or
      deaths in this series. The CPA can be divided into three levels - the cranial,
      medial, and caudal, and each level contains specific neurovascular structures as
      seen through the neuroendoscope. Knowledge of these divisions is useful to master
      the common NEAMN procedures of the CPA. NEAMN for CPA lesions via a retrosigmoid
      approach is a useful adjunct to standard microneurosurgical techniques effect and
      may decrease the operative risk.

PMID- 15851078
TI  - Irrigation vs. closed drainage in the treatment of chronic subdural hematoma.
AB  - A number of different techniques are used to treat chronic subdural hematomas
      surgically. In this study, 70 chronic subdural hematomas were surgically treated
      and analyzed prospectively. Patients were classified according to clinical
      features and computed tomography images. Results of the cases that underwent burr
      hole craniostomy-irrigation (group A; n=35) were compared with those undergoing
      burr-hole craniostomy-closed system drainage (group B; n=35). The most common
      etiological factor was trauma in both groups. Complete resolution in the early
      period was higher in group B compared to group A (60% vs. 40%). However, no
      difference was noted at the first month-follow-up. Recurrence rates were 17% in
      group A and 14% in group B. No significant difference was noted in terms of
      hospitalization duration or postoperative complications. In conclusion, we
      believe that the burr-hole craniostomy-irrigation technique is a reliable and
      effective method compared to burr-hole craniostomy-closed system drainage in the
      treatment of chronic subdural hematoma.

PMID- 15851079
TI  - Spinal cord stimulation: a seven-year audit.
AB  - OBJECTIVE: To evaluate the outcome and complications of spinal cord stimulation
      (SCS) for chronic neuropathic pain in an Australian population. MATERIALS AND
      METHODS: An independent researcher retrospectively examined the records of 138
      patients trialing SCS between 1995 and 2002 at our institution. Information
      collected included pain relief, ability to perform activities of daily living
      (ADLs), return to work and reduction in opiate analgesia. Clinical,
      psychological, demographic and financial data were also collected. RESULTS: Of
      138 patients who trialed SCS, 103 (74.7%) achieved a greater than 50% reduction
      in their pain and proceeded to permanent implantation. At 1 year following
      permanent implantation, 84.4% of these still had a reduction in their pain by
      greater than 50%. The majority of patients, 59.1%, stated that their analgesia
      was good (50-74% pain reduction). All patients required opiate analgesics prior
      to SCS implantation, but this fell to 54.6% after SCS implantation. Additionally,
      73.6% had a significant improvement in their ability to perform ADLs and 24% of
      patients were able to return to work. CONCLUSION: SCS is an effective treatment
      in the control of chronic neuropathic pain, particularly in combination with
      comprehensive medical management within a multidisciplinary pain management
      centre.

PMID- 15851080
TI  - Images in neuroscience: urge incontinence and an abnormal patch of skin.

PMID- 15851081
TI  - Increased xanthine oxidase activity after traumatic brain injury in rats.
AB  - Oxidative stress may contribute to many of the pathophysiologic changes that
      occur after traumatic brain injury (TBI). There are a number of potential sources
      and mechanisms for oxygen free radical (OFR) production and lipid peroxidation
      after TBI. In this study, we investigate the time-dependent changes in xanthine
      oxidase (XO) activity and lipid peroxidation using a focal TBI animal model. We
      demonstrate that there is an immediate increase in lipid peroxidation by-products
      and in XO enzyme activity after TBI.

PMID- 15851082
TI  - Severity-dependent expression of pro-inflammatory cytokines in traumatic spinal
      cord injury in the rat.
AB  - The post-traumatic inflammatory response in acute spinal cord contusion injury
      was studied in the rat. Mild and severe spinal cord injury (SCI) was produced by
      dropping a 10 g weight from 3 and 12 cm at the T12 vertebral level. Increased
      immunoreactivity of TNF-alpha in mild and severe SCI was detected in neurons at 1
      h post-injury, and in neurons and microglia at 6 h post-injury, with a less
      significant increase in mild SCI. Expression was short-lived and declined sharply
      by 1 d post-injury. RT-PCR showed an early significant up-regulation of IL-1
      beta, IL-6 and TNF-alpha mRNAs, maximal at 6 h post-injury with return to control
      levels by 24 h post-injury, the changes being less statistically significantly in
      mild SCI. Western blot showed early transient increases of IL-1 beta, IL-6 and
      TNF-alpha proteins in severe SCI but not mild SCI. Immunocytochemical, western
      blotting and RT-PCR analyses suggest that endogenous cells (neurons and
      microglia) in the spinal cord, not blood-borne leucocytes, contribute to IL-1
      beta, IL-6 and TNF-alpha production in the post-traumatic inflammatory response
      and that their up-regulation is greater in severe than mild SCI.

PMID- 15851083
TI  - Gene expression following traumatic brain injury in humans: analysis by
      microarray.
AB  - Global changes in gene expression were analyzed in pericontusional tissue taken
      during surgery from 4 patients with traumatic brain injury (TBI), in cerebral
      infarction tissue from a patient with vasculitis and in normal brain tissue
      resected during craniotomy for meningioma. Of approximately 1,200 genes showing
      some level of expression by cDNA microarray hybridization, 104 ( approximately
      8%) showed differential expression in traumatized tissue. Genes controlling
      transcriptional regulation, intermediary and energy metabolism, signal
      transduction, and intercellular adhesion and recognition were differentially
      affected most often. Four genes previously shown to be associated with TBI (c
      Fos, Jun B, HSP70, and Zif/268) were all found to be up-regulated in at least one
      TBI patient. Thus, the robust response to TBI of several immediate early genes is
      confirmed, and a longer list of candidate genes from other functional categories
      is suggested for further studies aimed at understanding the molecular and
      cellular consequences of TBI.

PMID- 15851084
TI  - Screening for unilateral intracranial abnormalities using near infrared
      spectroscopy: a preliminary report.
AB  - Near infrared spectroscopy (NIRS) is being increasingly used for medical
      applications, including neurosurgical care. This preliminary report describes the
      use of a low cost, indigenous, non-invasive system where NIRS is used to identify
      superficial unilateral intracranial abnormalities. The optical density (OD) over
      each hemisphere was initially studied in 50 normal volunteers. The specificity,
      sensitivity, reliability and reproducibility of the NIRS generated from the
      developed equipment in detecting OD were thus confirmed. The OD over each
      hemisphere was then measured in 71 other individuals, immediately after a
      computed tomography (CT) scan of the brain was performed. Data was statistically
      analysed to find the average OD difference (compared to the opposite side) of the
      various intracranial compartments. Differences in OD suggested a unilateral
      intracranial abnormality. All those in whom OD differences were detected with the
      NIRS system had unilateral abnormalities on the CT scan. None of the 53 patients
      who had a normal CT scan had significant differences in OD.

PMID- 15851085
TI  - Acute transverse myelitis due to Coxsackie virus.
AB  - The case of a young adult male, who after a short upper respiratory illness
      presented with fever and alarming progressive neurological deficits, is reported.
      The diagnostic puzzle and the difficulty in establishing a diagnosis are
      reported. Acute transverse myelitis is a rare clinical manifestation of Coxsackie
      virus infection, and very few cases of transverse myelitis caused by serotype B
      have been reported in the English literature. This is a case report of an unusual
      acute transverse myelitis caused by Coxsackie B2 infection.

PMID- 15851086
TI  - Adult acute disseminated encephalomyelitis associated with poststreptococcal
      infection.
AB  - Acute disseminated encephalomyelitis (ADEM) is a monophasic illness that is
      thought to develop from antigenic mimicry with antibodies having cross-reactivity
      to host epitopes in the nervous system. The disorder typically follows an
      exanthematous or recent viral infection. In contrast, complications from
      bacterial poststreptococcal infections more commonly give rise to disorders in
      the pediatric population including Sydenham's chorea, pediatric autoimmune
      neuropsychiatric disorders, and ADEM. We present the novel case of documented
      streptococcal pharyngitis and elevated antideoxyribonuclease B (ADNB) titers in
      an adult giving rise to ADEM. Furthermore, the absence of basal ganglia
      abnormalities on MRI and the degree of leukocytosis in the CSF distinguish the
      adult form of ADEM from childhood ADEM and adult viral demyelinating diseases.

PMID- 15851087
TI  - Petroclival mixed meningioma.
AB  - We present a 47-year-old lady with a large dumb-bell petroclival-cavernous sinus
      meningioma. The tumour was of mixed histopathology; the anterior part, in
      relationship to the cavernous sinus, was a syncitial meningioma and the posterior
      part in the petroclival region was a transitional meningioma. The two
      histological subtypes of meningioma within the same tumour displayed remarkable
      differences in their radiological features, nature of extensions, relationship
      with the adjoining structures and consistency. The clinical course of the two
      subtypes was also different. The unusual features of this case are reported and
      the relevant literature briefly reviewed.

PMID- 15851088
TI  - Wilson's disease with depression and parkinsonism.
AB  - Wilson's disease (WD) is an autosomal recessive disorder with reduced biliary
      excretion of copper plus impaired formation of ceruloplasmin, leading to copper
      accumulation in the liver, brain, kidney, and cornea. Clinical manifestations
      include liver damage, psychiatric symptoms, and neurological features. We report
      a 35-year-old woman with a history of deranged liver functions who had severe
      depression several years later and eventually presented with parkinsonian
      features. The underlying diagnosis is WD and family screening revealed WD in 2
      other siblings. She could not tolerate penicillamine because of fever and
      leucopenia. While taking trientine hydrochloride and zinc sulphate, her
      parkinsonism improved and her depression remained in remission. WD should be
      considered in patients with unexplained liver function derangement or psychiatric
      symptoms. Early diagnosis and initiation of specific treatment are crucial in
      minimising any further cerebral and hepatic damage as well as securing possible
      improvement in organ functions.

PMID- 15851089
TI  - Chondrosarcoma, lupus anticoagulant and cerebral ischaemia.
AB  - Chondrosarcoma is a malignant disease of cartilage. Systemic embolisation usually
      arises from cancerous invasion of pulmonary vessels or the left atrium but
      cerebral embolisation or ischaemia is rarely recognised. We report a man with
      left leg amputation for tibial myxoid chondrosarcoma who suffered multiple
      cerebral embolisms one year later. Cerebral angiography and aortogram did not
      reveal luminal stenosis and a cardiac survey was normal. Lupus anticoagulant
      (LAC) and a prolonged activated partial thromboplastin time were detected. A
      molecular mimicry between prothrombin and paracrine hormones may have accounted
      for his LAC. A procoagulant autoantibody reacting against metastatic cancer cells
      may contribute to cancerous thrombosis, such as in chondrosarcoma.

PMID- 15851090
TI  - Ectopic recurrence of craniopharyngioma.
AB  - A 50-year-old woman first presented with recurrent craniopharyngioma in the
      suprasellar region. The recurrent tumor was removed via the frontobasal
      interhemispheric approach. Two years later, magnetic resonance imaging revealed a
      further recurrence in the primary suprasellar region and a cystic mass with ring
      enhancement on the surface of the left frontal lobe. Both lesions were removed
      via the frontobasal interhemispheric approach. Histological examination showed
      the left frontal lesion was an ectopic recurrence of craniopharyngioma. Ectopic
      recurrence of craniopharyngioma is extremely rare.

PMID- 15851091
TI  - Two cases of pineal germinoma with granulomatous inflammation.
AB  - We report two cases of pineal germinoma with remarkable chronic granulomatous
      inflammation. In the first case, the pineal mass was totally removed via an
      occipital transtentorial approach as symptoms were due to direct mass effect. In
      the second case, endoscopic third ventriculostomy and tissue biopsy was performed
      to alleviate worsening hydrocephalus. Pathological examination of specimens of
      both cases showed chronic granulomatous inflammation associated with a few germ
      cell tumor nests, which demonstrated positive staining for placental alkaline
      phosphatase. Both patients received post-operative craniospinal irradiation with
      no subsequent neurological deficits. Follow-up magnetic resonance imaging (MRI)
      of the second case showed an asymptomatic, shrunken residual tumor mass. MRI of
      the first case showed no residual or recurrent disease. Thus, a pineal mass with
      unusual features on MRI and chronic granulomatous inflammation on histopathology,
      should raise the suspicion of germinoma. In cases with symptomatic mass effect,
      open resection can be considered. In cases with lesser mass effect, conventional
      therapeutic modalities without resection can achieve a good outcome, as for other
      germinomas.

PMID- 15851092
TI  - Intravenous immunoglobulin therapy for idiopathic postoperative lumbosacral
      plexopathy.
AB  - We report a patient who developed an acute lumbosacral plexopathy (LSP) following
      spinal surgery on lumbos segments. He recovered dramatically following treatment
      with high-dose intravenous immunoglobulin (IVIg). A 66-year-old man who underwent
      an L4 to S1 decompressive laminectomy required re-admission after developing
      contralateral leg pain. Follow-up lumbosacral magnetic resonance imaging showed
      only mild postoperative changes. Ten days after re-admission, he developed
      relatively rapid onset ipsilateral inguinal pain and weakness of all his leg
      muscles with diminished sensation in a lumbosacral plexus distribution. Re
      exploration revealed no specific lesion except for adhesions and resulted in no
      improvement. Following treatment with IVIg (0.4 g/kg daily) for five days, he
      showed dramatic resolution of motor weakness and pain. There has been no relapse
      following six months follow-up. Although IVIg treatment does not guarantee a
      positive response in all types of LSP, it should be considered for severe,
      rapidly progressive and even for postoperative cases.

PMID- 15851093
TI  - Bilateral profound hearing loss due to meningeal carcinomatosis.
AB  - Meningeal carcinomatosis (MC) is an uncommon form of metastasis of solid tumors.
      Hearing loss as the presenting symptom of MC is very uncommon. A patient with an
      esophageal signet ring cell carcinoma 3 years previously presented with sudden
      onset of profound hearing loss affecting both ears. He had no evidence of local
      tumor recurrence. Brain magnetic resonance imaging (MRI) showed swelling and
      increased signal intensity on T2 weighted images of both acoustic nerves and the
      right trigeminal nerve. After gadolinium administration, enhancement of both
      acoustic and trigeminal nerves was seen. He later developed unsteadiness and head
      movement-dependent oscillopsia due to vestibular areflexia and diplopia. At that
      time MRI showed leptomeningeal enhancement. MC was diagnosed, although
      cerebrospinal fluid cytology could not confirm that diagnosis. The patient died
      16 weeks after the onset of deafness. In patients with progressive unilateral and
      bilateral hearing loss, meningeal carcinomatosis should be considered, especially
      if there is a history of previous malignancy.

PMID- 15851094
TI  - Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating
      hormone.
AB  - Silent pituitary adenomas are a group of tumors showing heterogenous
      morphological features with no hormonal function observed clinically. To date no
      explanation has been provided as to why these tumors remain "silent". We report a
      case of a silent macroadenoma with both growth hormone (GH) and thyroid
      stimulating hormone (TSH) staining and secretion but with no clinical
      manifestations, in particular, the absence of features of acromegaly or
      hyperthyroidism. The relevant literature is reviewed.

PMID- 15851095
TI  - Delayed lymphocytic infundibuloneurohypophysitis following successful
      transsphenoidal treatment of Cushing's disease.
AB  - Lymphocytic infundibuloneurohypophysitis is a rare disorder in which
      neurohypophyseal function is impaired by an autoimmune process. Although several
      etiologies for this rare entity have been suggested, its occurrence following
      transsphenoidal adenomectomy has not been reported. A 20-year-old man presented
      with diabetes insipidus - seven years after successful transsphenoidal
      microadenomectomy for Cushing's disease, first diagnosed at the age of 13. Seven
      years later, he developed fairly rapid onset of polydipsia and polyuria. Magnetic
      resonance imaging demonstrated swelling of the posterior pituitary gland with
      thickening of the pituitary stalk. Endocrinological evaluation revealed
      neurohypophyseal dysfunction without the adenohypophysis being affected. On the
      basis of these findings, a diagnosis of lymphocytic infundibuloneurohypophysitis
      was made. The mass lesion of the posterior pituitary resolved after the
      administration of corticosteroids for two months and no operation was required.
      Lymphocytic infundibuloneurohypophysitis should be considered in the differential
      diagnosis of pituitary mass lesions following transsphenoidal surgery, especially
      when the mass is confined to the posterior pituitary gland with neurohypophyseal
      function being compromised.

PMID- 15851096
TI  - An unusual case of hypertensive encephalopathy.
AB  - This case report describes a 59-year-old male who presented with headaches,
      seizures and hypertension followed by coma. Initial magnetic resonance imaging
      showed T2 hyperintensities typical of Hypertensive Encephalopathy (HE), the
      follow up scans showed diffusion-weighted imaging (DWI) hyperintensities which is
      a rare finding in HE. DWI hyperintensities are typically suggestive of areas of
      cytotoxic damage, and the presence of these changes makes this case unusual,
      since the pathogenesis of HE is usually due to vasogenic oedema rather than
      cytotoxic damage of the brain tissue.

PMID- 15851097
TI  - Cerebellar liponeurocytoma.
AB  - A case of cerebellar liponeurocytoma in a 34-year-old man is reported. There are
      only 19 other cases reporting this entity in the medical literature. The
      diagnostic, radiological and clinical features associated with this tumour are
      reviewed and discussed in relation to our case. The differences in behaviour and
      prognosis between medulloblastoma and cerebellar liponeurocytoma are presented
      with the corresponding implications for management.

PMID- 15851098
TI  - Acute and reversible micrographia in a patient possibly due to cerebral
      ischaemia.
AB  - We report a patient who developed acute and reversible micrographia, presumably
      due to cerebral ischaemia, on a background of mutism following a pharyngo
      laryngectomy 10 years earlier. Magnetic resonance (MR) imaging showed chronic
      small vessel disease without evidence of an acute ischaemic lesion on diffusion
      weighted sequences. Our patient's micrographia improved significantly within 12
      days of symptom onset. The MR imaging was performed within 5 days of symptom
      onset, suggesting that the lesion was either too small for detection or had
      resolved on diffusion-weighted sequences.

PMID- 15851099
TI  - Biosynthesis of glyoxylate from glycine in Saccharomyces cerevisiae.
AB  - Glyoxylate biosynthesis in Saccharomyces cerevisiae is traditionally mainly
      ascribed to the reaction catalyzed by isocitrate lyase (Icl), which converts
      isocitrate to glyoxylate and succinate. However, Icl is generally reported to be
      repressed by glucose and yet glyoxylate is detected at high levels in S.
      cerevisiae extracts during cultivation on glucose. In bacteria there is an
      alternative pathway for glyoxylate biosynthesis that involves a direct oxidation
      of glycine. Therefore, we investigated the glycine metabolism in S. cerevisiae
      coupling metabolomics data and (13)C-isotope-labeling analysis of two reference
      strains and a mutant with a deletion in a gene encoding an alanine:glyoxylate
      aminotransferase. The strains were cultivated on minimal medium containing
      glucose or galactose, and (13)C-glycine as sole nitrogen source. Glyoxylate
      presented (13)C-labeling in all cultivation conditions. Furthermore, glyoxylate
      seemed to be converted to 2-oxovalerate, an unusual metabolite in S. cerevisiae.
      2-Oxovalerate can possibly be converted to 2-oxoisovalerate, a key precursor in
      the biosynthesis of branched-chain amino acids. Hence, we propose a new pathway
      for glycine catabolism and glyoxylate biosynthesis in S. cerevisiae that seems
      not to be repressed by glucose and is active under both aerobic and anaerobic
      conditions. This work demonstrates the great potential of coupling metabolomics
      data and isotope-labeling analysis for pathway reconstructions.

PMID- 15851100
TI  - Old yellow enzyme interferes with Bax-induced NADPH loss and lipid peroxidation
      in yeast.
AB  - The yeast transcriptional response to murine Bax expression was compared with the
      changes induced by H(2)O(2) treatment via microarray technology. Although most of
      the Bax-responsive genes were also triggered by H(2)O(2) treatment, OYE3, ICY2,
      MLS1 and BTN2 were validated to have a Bax-specific transcriptional response not
      shared with the oxidative stress trigger. In knockout experiments, only deletion
      of OYE3, coding for yeast Old yellow enzyme, attenuated the rate of Bax-induced
      growth arrest, cell death and NADPH decrease. Lipid peroxidation was completely
      absent in DeltaOYE3 expressing Bax. However, the absence of OYE3 sensitized yeast
      cells to H(2)O(2)-induced cell death, and increased the rate of NADPH decrease
      and lipid peroxidation. Our results clearly indicate that OYE3 interferes with
      Bax- and H(2)O(2)-induced lipid peroxidation and cell death in Saccharomyces
      cerevisiae.

PMID- 15851101
TI  - Lactose-induced cell death of beta-galactosidase mutants in Kluyveromyces lactis.
AB  - The Kluyveromyces lactis lac4 mutants, lacking the beta-galactosidase gene,
      cannot assimilate lactose, but grow normally on many other carbon sources.
      However, when these carbon sources and lactose were simultaneously present in the
      growth media, the mutants were unable to grow. The effect of lactose was
      cytotoxic since the addition of lactose to an exponentially-growing culture
      resulted in 90% loss of viability of the lac4 cells. An osmotic stabilizing agent
      prevented cells killing, supporting the hypothesis that the lactose toxicity
      could be mainly due to intracellular osmotic pressure. Deletion of the lactose
      permease gene, LAC12, abolished the inhibitory effect of lactose and allowed the
      cell to assimilate other carbon substrates. The lac4 strains gave rise, with
      unusually high frequency, to spontaneous mutants tolerant to lactose (lar1
      mutation: lactose resistant). These mutants were unable to take up lactose.
      Indeed, lar1 mutation turned out to be allelic to LAC12. The high mutability of
      the LAC12 locus may be an advantage for survival of K. lactis whose main habitat
      is lactose-containing niches.

PMID- 15851102
TI  - Enhanced secretion of heterologous proteins in Kluyveromyces lactis by
      overexpression of the GDP-mannose pyrophosphorylase, KlPsa1p.
AB  - GDP-mannose is the mannosyl donor for the glycosylation reactions and is
      synthesized by GDP-mannose pyrophosphorylase from GTP and d-mannose-1-phosphate;
      in Saccharomyces cerevisiae this enzyme is encoded by the PSA1/VIG9/SRB1 gene. We
      isolated the Kluyveromyces lactis KlPSA1 gene by complementing the osmotic growth
      defects of S. cerevisiae srb1/psa1 mutants. KlPsa1p displayed a high degree of
      similarity with other GDP-mannose pyrophosphorylases and was demonstrated to be
      the functional homologue of S. cerevisiae Psa1p. Phenotypic analysis of a K.
      lactis strain overexpressing the KlPSA1 gene revealed changes in the cell wall
      assembly. Increasing the KlPSA1 copy number restored the defects in O
      glycosylation, but not those in N-glycosylation, that occur in K. lactis cells
      depleted for the hexokinase Rag5p. Overexpression of GDP-mannose
      pyrophosphorylase also enhanced heterologous protein secretion in K. lactis as
      assayed by using the recombinant human serum albumin and the glucoamylase from
      Arxula adeninivorans.

PMID- 15851103
TI  - Molecular evidence for the existence of natural hybrids in the genus
      Zygosaccharomyces.
AB  - 26S rDNA D1/D2 sequencing was used to characterise a number of food-associated
      Zygosaccharomyces rouxii strains held at the National Collection of Yeast
      Cultures. In the course of this study, four strains (NCYC 1682, NCYC 3042, NCYC
      3060 and NCYC 3061) were identified which appeared, based on their D1/D2
      sequences, to belong to a novel Zygosaccharomyces species. However, subsequent
      sequence analysis showed that NCYC 1682, NCYC 3060 and NCYC 3061 possess two
      highly divergent copies of the nuclear-encoded ADE2, HIS3 and SOD2 genes,
      indicating these three strains are in fact hybrids. NCYC 3042, however, does
      appear to represent a novel species which may be hypothesized to have crossed
      with Z. rouxii and given rise to hybrid strains. Additional approaches to define
      precise taxonomic status and mechanisms of hybrid genome formation amongst yeast
      species are discussed.

PMID- 15851104
TI  - Bat2p is essential in Saccharomyces cerevisiae for fusel alcohol production on
      the non-fermentable carbon source ethanol.
AB  - Branched-chain amino acids (BCAAs) are key substrates in the formation of fusel
      alcohols, important flavour components in fermented foods. The first step in the
      catabolic BCAA degradation is a transaminase step, catalyzed by a branched-chain
      amino acid transaminase (BCAAT). Saccharomyces cerevisiae possesses a
      mitochondrial and a cytosolic BCAAT, Bat1p and Bat2p, respectively. In order to
      study the impact of the BCAATs on fusel alcohol production derived from the BCAA
      metabolism, S. cerevisiae BCAAT-deletion mutants were constructed. The BCAA l
      leucine was exogenously supplied during cultivations with mutants of S.
      cerevisiae. BAT1 deletion is not essential for fusel alcohol production, neither
      under glucose nor under ethanol growth conditions. The 3-methyl-1-butanol
      production rate of bat1Delta-cells on ethanol was decreased in comparison with
      that of wild-type cells, but the cells were still able to produce 3-methyl-1
      butanol. However, drastic effects in fusel alcohol production were obtained in
      cells lacking BAT2. Although the constructed bat2Delta-single deletion strain and
      the bat1Deltabat2Delta-double deletion strain were still able to produce 3-methyl
      1-butanol when grown on glucose, they were incapable of producing any 3-methyl-1
      butanol when ethanol was the sole carbon source available. In the circumstances
      used, gene expression analysis revealed a strong upregulation of BAT2 gene
      activity in the wild type, when cells grew on ethanol as carbon source.
      Apparently, the carbon metabolism is able to influence the expression of BCAATs
      and interferes with the nitrogen metabolism. Furthermore, analysis of gene
      expression profiles shows that the expression of genes coding for other
      transaminases present in S. cerevisiae was influenced by the deletion of one or
      both BCAATs. Several transaminases were upregulated when a BCAAT was deleted.
      Strikingly, none of the known transaminases was significantly upregulated when
      BAT2 was deleted. Therefore we conclude that the expression of BAT2 is essential
      for 3-methyl-1-butanol formation on the non-fermentable carbon source, ethanol.

PMID- 15851105
TI  - Deficiency of Pkc1 activity affects glycerol metabolism in Saccharomyces
      cerevisiae.
AB  - Protein kinase C is apparently involved in the control of many cellular systems:
      the cell wall integrity pathway, the synthesis of ribosomes, the appropriated
      reallocation of transcription factors under specific stress conditions and also
      the regulation of N-glycosylation activity. All these observations suggest the
      existence of additional targets not yet identified. In the context of the control
      of carbon metabolism, previous data had demonstrated that Pkc1p might play a
      central role in the control of cellular growth and metabolism in yeast. In
      particular, it has been suggested that it might be involved in the derepression
      of genes under glucose-repression by driving an appropriated subcellular
      localization of transcriptional factors, such as Mig1p. In this work, we show
      that a pkc1Delta mutant is unable to grow on glycerol because it cannot perform
      the derepression of the GUT1 gene that encodes glycerol kinase. Additionally,
      active transport is also partially affected. Using this phenotype, we were able
      to isolate a new pkc1Delta revertant. We also isolated two transformants
      identified as the nuclear exportin Msn5 and the histone deacetylase Hos2
      extragenic suppressors of this mutation. Based on these results, we postulate
      that Pkc1p may be involved in the control of the cellular localization and/or
      regulation of the activity of nuclear proteins implicated in gene expression.

PMID- 15851106
TI  - Expression of HPV16 E6 oncoprotein increases resistance to several stress
      conditions in Saccharomyces cerevisiae.
AB  - The E6 protein of human papillomavirus type 16 is essential for the oncogenic
      transformation process induced by these viruses. Here we expressed the E6 protein
      in Saccharomyces cerevisiae (which lacks p53) in order to determine if E6
      interacts with normal cell functioning, independently of the p53 tumour
      suppressor factor. We observed a higher resistance to caffeine, hydrogen peroxide
      and to pheromone, but not to high temperature, starvation and osmostress.
      Measurement of the relative expression levels of target genes of the signalling
      pathways, involved in the latter stressful stimuli, led us to conclude that such
      pathways are differently regulated in the presence of E6.

PMID- 15851108
TI  - Remodeling of myocyte gap junctions in arrhythmogenic right ventricular
      cardiomyopathy due to a deletion in plakoglobin (Naxos disease).
AB  - OBJECTIVES: We tested the hypothesis that defective interactions between adhesion
      junctions and the cytoskeleton caused by the plakoglobin mutation in Naxos
      disease lead to remodeling of gap junctions and altered expression of the major
      gap junction protein, connexin43. BACKGROUND: Naxos disease, a recessive form of
      arrhythmogenic right ventricular cardiomyopathy, is associated with a high
      incidence of arrhythmias and sudden cardiac death. Naxos disease is caused by a
      mutation in plakoglobin, a protein that links cell-cell adhesion molecules to the
      cytoskeleton. METHODS: Myocardial expression of connexin43 and other
      intercellular junction proteins was characterized in 4 patients with Naxos
      disease. Immunohistochemistry was performed in all 4 patients, and immunoblotting
      and electron microscopy were performed in 1 patient who died in childhood before
      overt arrhythmogenic right ventricular cardiomyopathy had developed. RESULTS:
      Connexin43 expression at intercellular junctions was reduced significantly in
      both right and left ventricles in all patients with Naxos disease. Electron
      microscopy revealed smaller and fewer gap junctions interconnecting ventricular
      myocytes. Mutant plakoglobin was expressed but failed to localize normally at
      intercellular junctions. Localization of N-cadherin, alpha- and beta-catenins,
      plakophilin-2, desmoplakin-1, and desmocollin-2 at intercalated disks appeared
      normal. CONCLUSIONS: Remodeling of gap junctions occurs early in Naxos disease,
      presumably because of abnormal linkage between mechanical junctions and the
      cytoskeleton. Gap junction remodeling may produce a coupling defect which,
      combined with the subsequent development of pathologic changes in myocardium,
      could contribute to a highly arrhythmogenic substrate and enhance the risk of
      sudden death in Naxos disease.

PMID- 15851109
TI  - The intercalated disk as a single functional unit.

PMID- 15851110
TI  - Epicardial organization of human ventricular fibrillation.
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that on the
      epicardium of the in vivo human heart, ventricular fibrillation (VF) consists of
      chaotic small wavefronts that constantly change paths. BACKGROUND: Despite the
      significance of VF to cardiovascular mortality, little is known about the
      wavefronts that constitute VF in humans. METHODS: In 9 patients undergoing
      cardiac surgery, a single VF episode was induced by rapid pacing immediately
      after institution of cardiopulmonary bypass while recordings were made from 504
      electrodes spaced 2 mm apart in a 20 cm(2) plaque held against the anterior left
      ventricle epicardium. A total of 26 segments of VF, each 2 s long, were analyzed.
      A computer algorithm identified individual wavefronts and classified them into
      groups that followed similar activation sequences. RESULTS: The mean activation
      rate was 5.8 +/- 1.8 (mean +/- SD) cycles/s. The wavefronts during each epoch
      were grouped into 9.4 +/- 7.1 different activation pathways, and 8.3 +/- 2.3
      wavefronts followed each pathway. Individual wavefronts spread to activate an
      area of 5.1 +/- 3.0 cm(2) in the mapped region. The majority of the wavefronts
      propagated into the mapped region and/or propagated out of the mapped region into
      adjacent tissue, suggesting that the wavefronts were larger than 5.1 cm(2).
      Reentry was identified in only 16 of the 26 (62%) 2-s segments, always completed
      <2 cycles, and lasted for 9.5 +/- 6.6% of these 16 epochs, which is 5.8% of the
      total duration of all the segments analyzed. CONCLUSION: VF wavefronts on the
      human epicardium are usually large, repeatedly follow distinct pathways, and only
      occasionally reenter. If these results for the left ventricular epicardium are
      representative of those for the entire ventricular mass, they do not support the
      hypothesis that human VF consists of small, constantly changing wavefronts, but
      rather suggest that there is significant organization of human VF.

PMID- 15851111
TI  - Ventricular fibrillation: an organized delirium or uncoordinated reason?

PMID- 15851112
TI  - Identification of preferential sites of parasympathetic input to the
      atrioventricular node in man.
AB  - OBJECTIVES: The effects of subthreshold stimulation performed at various sites in
      the perinodal and posteroseptal space on atrioventricular (AV) nodal conduction
      were investigated. BACKGROUND: The identification of specific or preferential
      sites of parasympathetic innervation to the AV node is suggested by observations
      made in both the animal and clinical laboratories. Pathologic studies of the
      parasympathetic innervation to the AV node show it is made up of serpiginous
      fibers traveling at highly specific sites within the myocardium endocardially
      towards the compact AV node. METHODS: We utilized endocardial subthreshold
      stimulation to selectively identify and characterize AV nodal inputs. Fourteen
      patients (age: 56 +/- 4 years) undergoing electrophysiologic testing with or
      without radiofrequency ablation for supraventricular tachycardia were studied. A
      steerable quadripolar catheter was positioned in 3 to 9 locations in the region
      between the site recording the His bundle electrogram and the coronary sinus (CS)
      os under flouroscopic and electroanatomic guidance. We mapped anterosuperior
      sites at or near sites with His potential recordings, and up to 2 mm inferior to
      the His bundle recording, posteroseptal sites included the CS os and sites along
      the posterior, superior, and inferior border of the CS. Atrial pacing was
      performed at a cycle length 50 ms longer than Wenckebach cycle length.
      Subthreshold stimulation was applied at a frequency of 10 Hz and 20 Hz delivered
      to the distal electrode pair. AH and HV intervals were recorded before and during
      subthreshold stimulation. AH prolongation was defined as a reproducible increase
      in AH interval by >10 ms from a stable baseline AH interval. RESULTS: Eight of 14
      patients demonstrated prolongation of AV conduction at a mean of 1.75 +/- 0.2
      sites. Mean AH prolongation was 56.4 +/- 13.0 ms (p = 0.02) from baseline. AH
      prolongation was achieved 15.4 +/- 1.8 mm below the His bundle recording in 7
      patients, at the site of the His bundle recording in 3 patients, and along the
      posterior CS os border in 3 patients. CONCLUSION: Subthreshold stimulation
      prolongs AV nodal conduction only at specific sites within the triangle of Koch,
      suggesting discrete parasympathetic endocardial inputs into the AV nodal region.

PMID- 15851113
TI  - Pulmonary vein antrum isolation for treatment of atrial fibrillation in patients
      with valvular heart disease or prior open heart surgery.
AB  - OBJECTIVES: The goal of this study was to assess the safety and efficacy of
      pulmonary vein antrum isolation in patients with moderate valvular heart disease
      or open-heart surgery and atrial fibrillation (AF). BACKGROUND: Valvular heart
      disease and open-heart surgery are commonly associated with AF and increase the
      risk of adverse events in AF patients. METHODS: A total of 391 consecutive
      patients who had pulmonary vein antrum isolation performed between December 2000
      and December 2002 were screened. A total of 142 of these patients had clinically
      significant valvular disease or prior cardiac surgery. End points included AF
      recurrence and pulmonary vein antrum isolation complication rates. RESULTS:
      Patients with valvular heart disease or prior open-heart surgery were older, had
      larger left atria and a more advanced New York Heart Association class. They did
      not differ significantly with respect to gender, but had a longer history of AF.
      Procedure times were similar between patients with and without valvular heart
      disease or prior open-heart surgery. After 18 +/- 7 months in the lone AF
      patients, 11 +/- 5 months in patients with valvular heart disease, and 10 +/- 5
      months in patients with prior open heart surgery, there was a trend toward lower
      recurrence of AF in patients with lone AF who enjoyed a 98% overall cure rate
      after up to 2 pulmonary vein antrum isolations versus 93% among patients with
      valvular heart disease (P = .04) and prior open heart surgery (P = .07).
      Complication rates were comparable between groups. CONCLUSIONS: Pulmonary vein
      antrum isolation is safe and effective in patients with moderate valvular heart
      disease and the patients who developed AF after open-heart surgery. These results
      have implications for our understanding of the pathophysiology of AF in patients
      with moderate valvular heart disease or past cardiac surgery and should be
      considered when discussing treatment options in these patients.

PMID- 15851114
TI  - Catheter ablation of atrial fibrillation: raising expectations for patients and
      physicians.

PMID- 15851115
TI  - Randomized comparison of anatomical versus voltage guided ablation of the
      cavotricuspid isthmus for atrial flutter.
AB  - OBJECTIVES: The purpose of this prospective study was to compare radiofrequency
      catheter ablation of the cavotricuspid isthmus using a strictly anatomic approach
      to an approach guided by a bipolar voltage map to avoid high voltage zones in the
      cavotricuspid isthmus. BACKGROUND: It is not clear whether local atrial
      electrogram amplitude influences the achievement of complete cavotricuspid
      isthmus block during radiofrequency catheter ablation for atrial flutter.
      METHODS: Thirty-two patients with atrial flutter were randomized to cavotricuspid
      isthmus ablation using an anatomical approach (group I, 16 patients) or guided by
      a bipolar voltage map (group II, 16 patients). A 3-dimensional electroanatomic
      mapping system and an 8-mm-tip ablation catheter were used in all patients. With
      the anatomical approach, an ablation line was created in the cavotricuspid
      isthmus at a 6 o'clock position in the 45 degree left anterior oblique
      projection. During voltage-guided ablation, a high-density bipolar voltage map of
      the cavotricuspid isthmus was created, and then contiguous applications of
      radiofrequency energy were delivered to create an ablation line through the
      cavotricuspid isthmus sites with the lowest bipolar voltage. RESULTS: Complete
      cavotricuspid isthmus conduction block was achieved in 100% of patients in each
      group. The mean maximum voltages along the line were 3.6 +/- 1.5 mV in group I,
      and 1.2 +/- 0.9 mV in group II (P < .01). Creating a high-density voltage map was
      associated with approximately 15-minute increase in the total procedure time (P =
      .2). During a mean follow-up of 177 +/- 40 days, there were no recurrences of
      atrial flutter in either group. There were no complications in either group.
      CONCLUSIONS: When cavotricuspid isthmus ablation for atrial flutter is performed
      with an 8-mm-tip catheter, complete block can be achieved in all patients
      regardless of local voltage. Ablation of high voltage zones is not associated
      with a higher recurrence rate. Therefore, anatomic ablation without voltage
      mapping is the preferred initial approach for cavotricuspid isthmus ablation.

PMID- 15851116
TI  - What is the best approach to ablation of typical atrial flutter?

PMID- 15851117
TI  - Standardized screening and treatment of patients with life-threatening
      arrhythmias: the Leiden out-of-hospital cardiac arrest evaluation study.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of a systematic
      screening/treatment protocol on outcome in patients after aborted sudden death.
      BACKGROUND: Patients after aborted sudden death are at high risk for recurrent
      events. In this regard, systematic screening is mandatory to reveal the
      underlying etiology, to detect and subsequently treat reversible causes, and to
      establish patient-tailored antiarrhythmic treatment. METHODS: A total of 417
      consecutive patients after aborted sudden death due to ventricular arrhythmias
      underwent echocardiography and coronary angiography. In the presence of coronary
      artery disease and myocardial ischemia, using stress-rest myocardial perfusion
      imaging/exercise testing, subsequent revascularization was performed. Patients
      without ischemic heart disease were further evaluated with magnetic resonance
      imaging, contrast echocardiography, right ventricular angiography and/or
      flecainide/ergonovine testing. After these diagnostic steps, final antiarrhythmic
      therapy was based on the outcome of electrophysiologic testing. RESULTS: The
      majority of patients had ischemic heart disease (n = 300, 72%). After screening,
      78 (78 of 300, 26%) patients underwent revascularization. In 69% of patients,
      ventricular arrhythmias were inducible during electrophysiologic testing. Therapy
      consisted of implantable defibrillators in 301 (72%) patients, antiarrhythmic
      drugs in 239 (57%) patients, and catheter ablation in 58 (14%) patients. During 5
      year follow-up, only 3 (<1%) patients died suddenly. The 5-year survival rate was
      82%; of 39 deaths, 10 (26%) patients died due to non-cardiac disease and 26 (67%)
      due to heart failure. CONCLUSIONS: Screening and treatment of patients after
      aborted sudden death according to a standardized protocol resulted in <1%
      arrhythmic deaths during 5-year follow-up. The majority of patients died of heart
      failure, stressing the importance of optimizing medical and surgical therapy and
      screening.

PMID- 15851118
TI  - The Leiden out-of-hospital cardiac arrest evaluation study (LOHCAT): a useful
      protocol: a critical process.

PMID- 15851119
TI  - Identification of a common genetic substrate underlying postpartum cardiac events
      in congenital long QT syndrome.
AB  - OBJECTIVES: The aim of this study was to elucidate the genetic basis for long QT
      syndrome (LQTS) in patients with a personal or family history of postpartum
      cardiac events. BACKGROUND: The postpartum period is a time of increased
      arrhythmogenic susceptibility in women with LQTS. METHODS: Between August 1997
      and May 2003, 388 unrelated patients (260 females, average age at diagnosis, 23
      years, and average QTc, 482 ms) were referred to Mayo Clinic's Sudden Death
      Genomics Laboratory for LQTS genetic testing. Comprehensive mutational analysis
      of the 5 LQTS-causing channel genes was performed. The postpartum period was
      defined as the 20 weeks after delivery. Cardiac events included sudden cardiac
      death, aborted cardiac arrest, and syncope. The presence of a personal and/or
      family history of cardiac events during postpartum period was determined by
      review of the medical records and/or phone interviews and was blinded to the
      status of genetic testing. RESULTS: Fourteen patients (3.6% of cohort) had
      personal (n = 4) and/or family history (n = 11) of cardiac events during the
      defined postpartum period. Thirteen of 14 patients (93%) possessed an LQT2
      mutation and 1 had an LQT1 mutation. Postpartum cardiac events were found more
      commonly in patients with LQT2 (13 of 80, 16%) than in patients with LQT1 (1 of
      103, <1%, P = .0001). CONCLUSIONS: There is a relatively gene-specific molecular
      basis underlying cardiac events during the postpartum period in LQTS. Along with
      previous gene-specific associations involving swimming and LQT1 as well as
      auditory triggers and LQT2, this association between postpartum cardiac events
      and LQT2 can facilitate strategic genotyping.

PMID- 15851120
TI  - Congenital long QT syndrome: looking beyond the heart.

PMID- 15851121
TI  - Effect of stretch-activated channels on defibrillation efficacy.
AB  - OBJECTIVES: This study aims to explore whether defibrillation threshold elevation
      could be caused by sustained recruitment of stretch-activated channels (SACs)
      and, if so, what are the underlying mechanisms. BACKGROUND: Clinical studies have
      demonstrated that patients with dilated and overloaded ventricles have elevated
      defibrillation threshold. Prolonged ventricular stretch has been suggested as a
      possible factor in defibrillation threshold elevation; however, its role remains
      unclear. METHODS: A two-dimensional finite-element bidomain model of ventricular
      defibrillation was used in the study. Retaining the geometrical parameters in the
      model, defibrillation dose-response curves were constructed with and without SACs
      to isolate the effect of stretch on shock outcome. RESULTS: Simulations
      demonstrate that SAC activation leads to flattening of dose-response curve and
      increases in defibrillation threshold and effective dose for defibrillation by
      31.4% and 18.8%, respectively. Examination of the electrophysiologic properties
      associated with sustained SAC recruitment pinpointed the main mechanisms
      responsible for the decrease in defibrillation efficacy. The lower conduction
      velocity of the shock-induced break excitations and the more positive
      transmembrane potential at the end of the effective refractory period in the
      tissue with SACs are proposed as main reasons for defibrillation threshold
      elevation. CONCLUSIONS: Demonstrating the contribution of SACs to defibrillation
      threshold elevation identifies SACs as an attractive pharmaceutical target to
      reduce defibrillation threshold in patients with dilated cardiomyopathy.

PMID- 15851122
TI  - Pulmonary vein occlusion: an unanticipated complication of catheter ablation of
      atrial fibrillation using the anatomic circumferential approach.
AB  - Favorable results of circumferential pulmonary vein (PV) ostial ablation guided
      by electroanatomic mapping (Carto) have fueled great enthusiasm for this
      technique. The lesion set for this ablation procedure as described by Pappone et
      al.(1,2) involves a figure of 8 lesions encompassing the 2 right and 2 left PV
      ostia with 2 additional linear lesions. Pulmonary vein stenosis/or occlusion has
      not previously been reported as a complication of this procedure. We describe PV
      occlusion after this procedure. Based on the occurrence of this previously
      unreported complication, we no longer create a figure '8' lesion around the right
      superior and inferior PVs. We anticipate that this complication can be avoided by
      creating a circular lesion encompassing the 2 PV ostia, while avoiding the linear
      lesion between the 2 PV ostia.

PMID- 15851123
TI  - Typical counterclockwise atrial flutter occurring despite absence of the inferior
      vena cava.
AB  - A 74-year-old man with a structurally normal heart presented with typical atrial
      flutter, after treatment of atrial fibrillation with propafenone. Catheterization
      and computed tomographic imaging revealed absence of the inferior vena caval
      segment that normally traverses the liver to enter the right atrium. Abdominal
      venous return occurred via the hemi-azygous vein, draining into the superior vena
      cava. Hepatic veins inserted postero-inferiorly into the right atrium. Pacing
      atrial myocardium between the hepatic veins and the tricuspid valve resulted in
      concealed entrainment. Radiofrequency catheter ablation directed (via a superior
      approach from the right internal jugular vein) to this extraordinary "isthmus"
      abolished atrial flutter. The implications of this congenital abnormality on
      posterior barriers maintaining the atrial flutter circuit are discussed.

PMID- 15851124
TI  - Novel use of postpacing interval mapping to guide radiofrequency ablation of
      focal atrial tachycardia with long intra-atrial conduction time.
AB  - If the intra-atrial conduction time of a focal tachycardia is prolonged and
      exceeds the tachycardia cycle length, isochronal electroanatomical maps may be
      confusing by not showing the classical centrifugal pattern of focal activation.
      In addressing the hypothesis that by mapping post pacing intervals (PPI), the
      shortest PPI (ideally identical to tachycardia cycle length) would clearly
      display the site of origin of a focal tachycardia; this technique was used
      successfully to identify the origin and ablate the atrial tachycardia of a
      patient with previously corrected Tetralogy of Fallot.

PMID- 15851125
TI  - From bedside to bench: entrainment and other stories.
AB  - The concepts of transient entrainment of reentrant rhythms started with studies
      of overdrive pacing of atrial flutter (AFL) in patients in the immediate period
      after open heart surgery. Initial studies demonstrated the need to achieve a
      critical pacing rate and a critical duration of pacing at the critical pacing
      rate to interrupt AFL. Further pacing studies of AFL, ventricular tachycardia,
      atrioventricular (AV) reentrant tachycardia, AV nodal reentrant tachycardia, and
      atrial tachycardia refined the understanding of what occurs during overdrive
      pacing of reentrant tachycardias, and permitted a mechanistic understanding of
      transient entrainment as continuous resetting of a reentrant tachycardia to a
      pacing rate that is faster than the rate of the tachycardia, but which fails to
      interrupt it. The demonstration of transient entrainment of a tachycardia
      provides a reliable clinical tool to establish the presence of a reentrant
      rhythm. Moreover, the principles of entrainment have also been applied clinically
      to assist in effective application of antitachycardia pacing and catheter
      ablation techniques.

PMID- 15851126
TI  - A review of the coronary venous system: a road less travelled.
AB  - Compared with the coronary arterial system, less attention has been paid to the
      coronary venous system. In the current era, there are therapeutic options for
      arrhythmias and for heart failure that use the coronary venous system to access
      target areas. We review the arrangement of the main cardiac veins to provide a
      morphologic background to interventionists. In general, the venous system is a
      useful conduit for delivery of percutaneous transcatheter treatment. But,
      variability in terms of valves, diameter, angulation, extent of muscular sleeves,
      proximity to other cardiac structures, and cross-over spatial relationship with
      branches of coronary arteries have implications for practitioners seeking to make
      use of the system.

PMID- 15851127
TI  - The coronary sinus: passive bystander or source of arrhythmia?
AB  - The coronary sinus provides access to the epicardial space of the heart allowing
      ablation of epicardial accessory pathways, foci of ventricular arrhythmia, and
      arrhythmogenic areas such as the vein or ligament of Marshall. In addition, its
      musculature may form atrioventricular accessory connections, participate in
      macroreentrant atrial arrhythmias, and generate foci of microreentrant atrial
      tachycardia and fibrillation. Thus, the coronary sinus may serve both as a
      bystander to arrhythmia circuits as well as an original source of cardiac
      arrhythmia.

PMID- 15851128
TI  - Atrial fibrillation: focal activity, re-entry, or both?

PMID- 15851129
TI  - A preexcited tachycardia: what is the mechanism?

PMID- 15851130
TI  - 2:1 AV tracking during DDD pacing during high output ventricular stimulation.

PMID- 15851132
TI  - Overview of symposium: outcomes in AF trials.

PMID- 15851133
TI  - Overview of endpoints in atrial fibrillation studies.
AB  - Among the principles for selection of endpoints for trials of arrhythmia
      management, the most important is that the endpoint be clinically relevant.
      According to this principle, the endpoint must be closely related to the
      objective of therapy. In the case of atrial fibrillation, for too long it seems,
      it has been believed that the primary objective of therapy has been maintenance
      of sinus rhythm. However, it is important to recognize that maintenance of sinus
      rhythm is, in fact, a surrogate endpoint and, as the lesson of the Cardiac
      Arrhythmia Suppression Trial has taught us, arrhythmia suppression is not
      necessarily a good surrogate for clinical events of importance. The use of
      clinical events as endpoints is to be encouraged, but the problem is that these
      events occur with a low frequency in many patients with atrial fibrillation.
      Symptoms are a primary target of therapy and potentially a good endpoint, but
      good methodology for quantification of symptoms remains to be developed.
      Methodology for assessment of patient-perceived quality of life is more highly
      developed. Surrogate endpoints, such as measurement of sinus rhythm or heart rate
      control, have the dual problems that they have not been well calibrated with
      clinical events and they sometimes are overly precise. Other surrogates have not
      been investigated. Composite endpoints are potentially useful, and cost is an
      important endpoint. More research on the validity of some of these endpoints is
      needed if we are to advance our knowledge of the management of atrial
      fibrillation in a meaningful way.

PMID- 15851134
TI  - Mortality as an endpoint in atrial fibrillation.
AB  - The aim of this study was to evaluate the use of mortality as an appropriate
      endpoint in studies of atrial fibrillation. Almost none of the atrial
      fibrillation trials has shown a significant difference in mortality among the
      various treatment arms because the studies are small, and many patient-years are
      required to show significant differences. Differences can be found when mortality
      is used as part of a combined endpoint and in meta-analyses of atrial
      fibrillation trials. Some trials of atrial fibrillation in the setting of
      conditions predisposing to high mortality, such as heart failure, postmyocardial
      infarction, and perioperative state for surgical procedures, can have mortality
      differences. Nevertheless, mortality has a role in validating the safety of new
      therapies and can be used as a measure of the impact and prognostic significance
      of atrial fibrillation in various disease settings.

PMID- 15851135
TI  - Quality of life as an endpoint for atrial fibrillation research: pitfalls and
      practice.
AB  - There have been few health-related quality-of-life (HR-QOL) studies of atrial
      fibrillation in nontreated cohorts, even though it often is used as an endpoint
      in clinical trials. Nonintervention data now available are selected for those in
      whom novel therapies are most often offered. These data suggest that atrial
      fibrillation confers an HR-QOL impact commensurate with postangioplasty and
      significant coronary disease groups. The correlation of HR-QOL measures and
      formal measures of atrial fibrillation "burden" (frequency or duration) is either
      poor or unknown (in the case of permanent atrial fibrillation). HR-QOL tools,
      although relevant, may not be as precise as traditional outcome measures. As a
      result, a 0.5 standard deviation unit of change in scale is needed to be
      considered moderate. There is a need to use validated instruments that are
      hypothesized to be sensitive to any intervention under study. The most studied
      area in atrial fibrillation has been that of ablation and pacing as rate control
      strategy. Depending on selection bias, SF-36 full standard deviation unit changes
      have been observed. Less controlled studies have documented significant benefit
      to left atrial ablative strategies. Device- and drug-based strategies in atrial
      fibrillation management have not demonstrated significant HR-QOL benefits, other
      than one controlled evaluation of an atrial defibrillator. Further study is
      needed both to refine instrument precision and to translate HR-QOL data into the
      denominator of cost-efficacy evaluations.

PMID- 15851136
TI  - Atrial fibrillation endpoints: hospitalization.

PMID- 15851137
TI  - Symptomatic arrhythmia recurrence as an outcome in clinical trials of
      antiarrhythmic drug therapy.
AB  - Atrial fibrillation is the most common cardiac arrhythmia requiring medical
      treatment, and developing new antiarrhythmic therapies remains a challenging
      problem. Documenting symptomatic arrhythmia recurrence using patient-activated
      ECG recording has been a useful tool to test new pharmacologic therapies. This
      technique has been used successfully to test immediate-release verapamil in
      patients with paroxysmal supraventricular tachycardia; flecainide acetate in
      patients with atrial fibrillation and paroxysmal supraventricular tachycardia;
      immediate-release propafenone in patients with atrial fibrillation and paroxysmal
      supraventricular tachycardia; d,l-sotalol in patients with atrial fibrillation;
      digoxin in patients with atrial fibrillation; azimilide dihydrochloride in
      patients with atrial fibrillation; and sustained-release propafenone in patients
      with atrial fibrillation. These studies have contributed to understanding
      efficacy and have led to regulatory approvals in the United States to label drugs
      as effective for supraventricular arrhythmias.

PMID- 15851138
TI  - Are there alternatives to mortality as an endpoint in clinical trials of atrial
      fibrillation?
AB  - Although atrial fibrillation (AF) is associated with an increased risk of death
      in many cohort studies and, therefore, is an endpoint of interest in trials of
      management of AF, the frequency of occurrence is low. Arrhythmia suppression as a
      surrogate endpoint for mortality in trials of rhythm management has a bad
      reputation. Recently, rehospitalization has been suggested as a possible
      surrogate for mortality in patients with potentially lethal ventricular
      arrhythmias. The prospect of alternatives to mortality in studies of patients
      with AF has been explored in the Atrial Fibrillation Follow-up Investigation of
      Rhythm Management (AFFIRM) trial. That analysis suggested that hospitalization
      for cardiovascular reasons (CV hospitalization) in patients such as those
      enrolled in AFFIRM may have many characteristics of a good surrogate for
      mortality. Furthermore, modeling based on the AFFIRM research plan and using CV
      hospitalization in a composite endpoint with death from all causes as an
      alternative to death alone provides ample power to detect even modest differences
      (>/=15%) with substantial reduction of the number of subjects that need to be
      enrolled. However, there are limitations in the AFFIRM data on these points. More
      research is needed to define suitable alternatives to death as an endpoint for
      trials in a broad spectrum of patients with AF.

PMID- 15851139
TI  - Ventricular rate control as an endpoint for treatment of atrial fibrillation.
AB  - Interest in the use of rate control as an endpoint for managing atrial
      fibrillation likely will increase given the results of recent randomized clinical
      trials. As an endpoint, rate control has favorable attributes of ease of
      measurement and clear numerical definitions. Pharmacologic rate control is
      achieved in approximately 80% of patients in large clinical trials. Ablation and
      pacing may achieve rate control in all patients. Rate control has been shown to
      improve quality of life over pretreatment status. However, several issues
      regarding the use of rate control as an endpoint are unsettled. Technical issues
      concerning when and how to measure heart rate remain. The current definitions of
      rate control are lacking in scientific foundation and demonstration of clinical
      relevance. Heart rate control during exercise may be difficult to achieve in many
      patients despite control at rest. Finally, the relationship of rate control to
      some important clinical outcomes has not been established.

PMID- 15851140
TI  - Rhythm control in atrial fibrillation: endpoints for device-based trials.
AB  - Newer generations of pacemakers and implantable cardioverter defibrillators have
      enhanced diagnostic features that permit detection and storage of information
      about the frequency, duration, time of onset, and rate characteristics of
      multiple consecutive episodes of atrial tachycardia and atrial fibrillation (AF).
      Parameters available in implantable devices that might serve as outcome measures
      to assess the impact of pharmacologic and nonpharmacologic therapies for
      prevention of AF include time to first recurrence of AF, intervals between
      successive episodes of AF, AF frequency, AF duration, AF burden (amount/unit
      time), and episodes of symptomatic AF. Each parameter has advantages and
      limitations. The characteristics/temporal patterns of AF may determine the ideal
      study outcome measure to address a specific hypothesis. Clinical studies of
      therapies for prevention of AF need to be directed to populations with the
      arrhythmia substrate that will be targeted by the therapy. Device-based metrics
      are suitable to assess the impact of pacing or pharmacologic therapies for
      prevention of AF. However, it is important to establish that suppression of AF is
      associated with an improvement in some clinical outcome. Relevant outcomes might
      include improvement in symptoms, quality of life, or functional capacity;
      reduction in hospitalization for cardiovascular causes, stroke death, or overall
      mortality; or a composite of some of these parameters.

PMID- 15851141
TI  - Sample size estimates for atrial fibrillation endpoints.
AB  - This article reviews the current sample size requirements for studies evaluating
      the efficacy of atrial therapies. Sample sizes for several study designs and
      endpoints are presented. However, emphasis is given to studies conducted in
      patients with implantable devices in the light of new available data from recent
      trials involving such patients. Studies utilizing mortality require >5,000
      patients followed for at least 2 years. Symptomatic episode recurrence represents
      a possible alternate endpoint but still requires >400 patients followed for 1
      year. Parallel design studies for device atrial fibrillation (AF) burden and
      frequency endpoints were found to be of little value because they would require
      thousands of patients. In contrast, cross-over studies utilizing device AF burden
      or AF frequency endpoints provide the best option in terms of sample size and
      study duration. A 30% therapy efficacy (reduction in AF burden or frequency) can
      be detected with just a little over 100 patients followed for 6 months.
      Therefore, cross-over studies with device-based endpoints are a viable option to
      evaluate and screen possible new rhythm control treatments before evaluating
      their effect on clinical outcome variables that may require larger trials with
      longer follow-up times.

PMID- 15851142
TI  - Diagnostic information in implantable devices that pertain to endpoints in atrial
      fibrillation studies.
AB  - Implantable devices can store significant information about physiologic
      parameters relating to rhythm and rate control. The primary objective of our
      analysis was to evaluate the relationship between changes in these parameters and
      changes in clinical outcomes in patients with atrial tachyarrhythmias (AT).
      Because the present guidelines do not provide quantitative definition of rhythm
      and rate control, we used the percent of time in AT and frequency of such
      episodes as measures of rhythm control. Rate control was measured as the percent
      of time spent at a ventricular rate >120 beats/min, as well as the median
      ventricular rate during AT. Analysis was conducted in 643 patients with a history
      of AT and bradycardia receiving pacemakers to evaluate whether changes in these
      parameters were correlated with changes in cardiac hospitalization rates and SF
      36 and symptom checklist scores. All patients were followed at 1, 4, and 7 months
      postimplant, during which rhythm and rate control data were collected. Positive
      correlation was observed between changes in cardiac hospitalization rate and
      changes in AT burden, as well as frequency of AT (P = 0.01, r = 0.08 for each).
      Changes in SF-36 or symptom checklist scores did not correlate with changes in
      rhythm and rate control measures. This patient cohort had relatively asymptomatic
      atrial fibrillation (symptom checklist frequency and severity scores of 14.3 +/-
      9.5 and 11.5 +/- 7.9, respectively), and this may have contributed to the lack of
      correlation with SF-36 and symptom scores. Data stored in implantable devices
      offer a unique opportunity to monitor parameters of rhythm as well as rate
      control in patients with AT. In patients implanted with pacemakers for management
      of bradyarrhythmias who have a history of AT, a significantly positive but weak
      correlation was observed between changes in rhythm control measures (AT burden
      and frequency) and changes in cardiac hospitalization rate.

PMID- 15851143
TI  - Catheter cryoablation of supraventricular tachycardia: results of the multicenter
      prospective "frosty" trial.
AB  - OBJECTIVE: To study the safety, efficacy, and mapping utility of a new
      cryoablation catheter. BACKGROUND: The CryoCath Technologies Freezor catheter has
      been used successfully for cryoablation of supraventricular tachycardia (SVT),
      but has not been evaluated in a large clinical trial. METHODS: A multicenter
      clinical trial to evaluate the safety, efficacy, and cryomapping utility of this
      cryoablation catheter was conducted in 166 subjects. The target of ablation was
      the slow pathway in patients with SVT due to AV nodal reentry (AVNRT, n = 103),
      an accessory pathway in patients with AV reentrant SVT (AVRT, n = 51) and the AV
      junction in patients with atrial fibrillation (AF, n = 12). RESULTS: Acute
      procedural success (APS) was achieved in 83% of the overall group (95% CI, 76% to
      88%). APS in the AVNRT group was 91% (98.3% CI, 82% to 97%), compared to 69% for
      AVRT (98.3% CI, 51% to 84%) and 67% for AF (98.3% CI, 29% to 93%), a highly
      significant difference (P < .001 by stepwise logistic regression). In patients
      with APS, long-term success after 6 months was 91% overall (95% CI, 86% to 96%)
      and 94% for AVNRT subjects (98.3% CI, 87% to 100%). None of the AVNRT or AVRT
      subjects required a permanent pacemaker. Cryomapping successfully identified
      ablation targets in 64% of patients in whom it was attempted. The
      electrophysiologic effects of cryomapping were completely reversible within
      minutes in 94% of such attempts. CONCLUSIONS: Catheter cryoablation of SVT is a
      safe alternative to RF ablation and is clinically effective in patients with
      AVNRT. Cryomapping can reversibly identify targets for ablation and can help
      minimize the risk of inadvertent AV block during ablation.

PMID- 15851144
TI  - Catheter cryoablation of supraventricular tachycardia: Quo vadis?

PMID- 15851145
TI  - Global remodeling of the ventricular interstitium in idiopathic myocardial
      fibrosis and sudden cardiac death.
AB  - OBJECTIVE: Characterization of a distinct, and as yet unexplained phenotype of
      sudden cardiac death (SCD). BACKGROUND: In a subgroup of patients with SCD,
      postmortem findings are limited to isolated idiopathic myocardial fibrosis (IMF).
      The absence of confounding factors may facilitate evaluation of the relationship
      between myocardial fibrosis and ventricular arrhythmogenesis. METHODS: Six
      patients with IMF were identified from a postmortem, consecutive 13-year series
      of 270 subjects presenting with SCD. Ventricular interstitial remodeling was
      assessed quantitatively and qualitatively and comparisons made with 6 age- and
      sex-matched control subjects who suffered noncardiac death. Myocardial collagen
      volume fraction and perivascular fibrosis ratio were determined and evidence for
      inflammatory response and apoptotic cell death was sought. The potential role of
      transforming growth factor beta 1 (TGF-beta(1)) in the pathogenesis of IMF was
      evaluated. RESULTS: Overall myocardial collagen volume fraction was 1.6-fold
      higher in IMF (mean age 34 +/- 4 yrs) vs. controls (mean age 34 +/- 4 yrs, .022
      +/- .001 vs .013 +/- .001; P < .001). Collagen volume fraction increase was
      diffuse but disproportionately so in the LV inferior wall (3.4-fold increase;
      .035 +/- .005 vs .012 +/- .018; P < .001). Perivascular fibrosis ratio was also
      increased (.770 +/- .014 vs .723 +/- .010; P = .007). There was no evidence of
      either myocardial inflammatory response or myocyte apoptosis in cases or
      controls. Expression of TGF-beta(1) was significantly increased in IMF vs
      controls. CONCLUSION: IMF involves diffuse and heterogeneous remodeling of the
      ventricular interstitium, with a predilection for the LV inferior wall. TGF
      beta(1) is a potential mediator of interstitial remodeling in IMF and SCD.

PMID- 15851146
TI  - Patient, procedural, and hardware factors associated with pacemaker lead failures
      in pediatrics and congenital heart disease.
AB  - OBJECTIVES: To examine outcomes of children with pacemakers over a 22-year period
      and identify risk factors for lead failure. BACKGROUND: Small patient size,
      structural cardiac abnormalities, and growth may complicate pediatric pacemaker
      management. Better knowledge of risk factors for lead failure in these patients
      may help improve future outcomes. METHODS: All pacemaker patients followed at one
      pediatric center 1980-2002 were included. Lead failures were identified
      retrospectively as leads repaired, replaced, or abandoned due to fracture,
      insulation break, dislodgement, or abnormalities in pacing or sensing. Risk
      factors were identified using logistic regression and Cox analyses. RESULTS: A
      total of 1007 leads were implanted in 497 patients during the study period (5175
      lead-years). Median age at implant was 9 years (0-55); 64% of patients had
      structural congenital heart disease. Median follow-up time was 6.2 years (0-22).
      Lead failure occurred in 155 leads (15%), and 115 patients (23%), with 28% of
      patients experiencing multiple failures. Significant independent correlates of
      lead failure included age <12 years at implant, history of structural congenital
      heart defects, and epicardial lead placement. Younger patients (<12 years)
      experienced significantly more lead fractures than older children (P = .005),
      while patients with congenital heart defects experienced more exit block.
      Epicardial leads were more likely to fail due to fracture or exit block, while
      transvenous leads failed more due to insulation breaks or dislodgements.
      CONCLUSIONS: Pediatric pacing patients have a high incidence lead failures. These
      occur most commonly in younger patients, structural congenital heart disease, and
      those with epicardial lead systems. Approaches to pacing system implantation and
      follow-up in these patients need to be individualized, with special attention to
      minimizing risk of lead failures. Our findings suggest that expanded utilization
      of transvenous systems in smaller patients seems justified when anatomy permits.

PMID- 15851147
TI  - Randomized pilot study of a new atrial-based minimal ventricular pacing mode in
      dual-chamber implantable cardioverter-defibrillators.
AB  - OBJECTIVE: We hypothesized that a new minimal ventricular pacing mode (MVP) that
      provides AAI/R pacing with ventricular monitoring and back-up DDD/R pacing as
      needed during AV block (AVB) would significantly reduce cumulative percent
      ventricular pacing compared to DDD/R. BACKGROUND: Conventional DDD/R mode often
      results in high cumulative percent ventricular pacing that may adversely affect
      ventricular function and increase risk of heart failure and atrial fibrillation.
      METHODS: MVP was made operational in 30 patients with DDD/R implantable
      cardioverter-defibrillators (ICDs) and no history of AVB. Patients were
      randomized to one week each in DDD/R and MVP. Holter monitor recordings (ECG,
      intracardiac electrograms, and event markers) and device diagnostics were
      analyzed for cumulative % atrial paced (Cum%AP), cumulative percent ventricular
      pacing, and frequency and duration of DDD/R pacing back-up. Diaries were used to
      report symptoms. RESULTS: Age of the study population was 61 years +/- 12 years
      and 83% were male. Baseline PR interval was 204 ms +/- 32 ms and programmed AV
      intervals (DDD/R) were 200 ms +/- 50 ms (paced)/167 ms +/- 54 ms (sensed). Cum%AP
      was similar between MVP and DDD/R (47.9 +/- 37 vs 46.3 +/- 36). Cumulative
      percent ventricular pacing was significantly lower in MVP vs DDD/R (3.79 +/- 16.3
      vs 80.6 +/- 33.8, P < .0001). Back-up DDD/R pacing during MVP operation due to
      transient AVB occurred in 10% of patients (9.3 +/- 7.4 [range 1-15]
      episodes/patient-day, duration 39.7 minutes +/- 156 minutes). Fifteen percent of
      AV intervals during MVP operation exceeded 300 ms. No significant symptoms were
      reported during MVP operation. CONCLUSIONS: MVP dramatically reduced cumulative
      percent ventricular pacing compared to DDD/R while maintaining AV synchrony and
      providing sensor-modulated atrial pacing support. Intermittent oscillations
      between MVP and DDD/R during transient AV block appeared safe and well tolerated.

PMID- 15851148
TI  - Outcomes of radiofrequency catheter ablation of atrioventricular reciprocating
      tachycardia in patients with congenital heart disease.
AB  - OBJECTIVES: Assessment of clinical outcomes of catheter ablation of
      atrioventricular reciprocating tachycardias in patients with congenital heart
      disease (CHD). BACKGROUND: Atrioventricular reciprocating tachycardias occur in
      patients with CHD and may be poorly tolerated. METHODS: Retrospective review of
      all 105 such ablations in 83 patients performed between 03/90 and 02/02 at one
      institution. RESULTS: The dominant arrhythmia mechanism was accessory pathway (70
      patients, 84%), and the most common indications were drug-refractory tachycardia,
      life-threatening arrhythmia, and elective presurgical ablation. Congenital heart
      disease diagnoses were diverse, with one third of patients having Ebstein's
      anomaly. Twenty patients (24%) had catheter access limited by prior surgeries or
      occluded vascular access. Of 109 accessory pathways (APs), 74 (68%) were
      manifestly preexcited, and 71 (65%) were located on the right atrioventricular
      groove. Fourteen patients (20%) had multiple pathways. There were 2 major
      complications (1 death, 1 hemorrhage), and 3 minor complications (5.5% of
      procedures). Acute success rate was 80% per procedure, 82% for left- and 70% for
      right-sided APs. Acute success rates for patients with Ebstein's anomaly were
      similar to patients with other CHD diagnoses, but Ebstein's patients were more
      likely to have recurrence. At 44 +/- 35 months follow-up, successful ablation was
      achieved in 59% of procedures and 68% of patients, with 19 patients (23%)
      undergoing one or more repeat ablations. CONCLUSIONS: Compared to patients with
      normal cardiac anatomy, patients with CHD of all varieties have lower rates of
      acute and long-term success for ablation for atrioventricular reciprocating
      tachycardias.

PMID- 15851149
TI  - Radiofrequency ablation in congenital heart disease: a call to arms.

PMID- 15851150
TI  - Electrophysiologic and clinical consequences of linear catheter ablation to
      transect the anterior left atrium in patients with atrial fibrillation.
AB  - OBJECTIVES: To evaluate the feasibility and outcome of ablation to transect the
      anterior left atrium (LA) in patients with atrial fibrillation (AF). BACKGROUND:
      While the Maze procedure is effective in maintaining sinus rhythm in patients
      with AF, it is associated with significant morbidity. This prospective clinical
      study evaluates the feasibility and consequences of limited LA linear ablation to
      transect the anterior LA in patients with AF. METHODS: Twenty-four patients (51.2
      +/- 7.3 years) with paroxysmal (n = 16) or chronic (n = 8) AF resistant to
      pulmonary vein (PV) isolation were studied. To transect the anterior LA, linear
      ablation was performed joining the superior PVs; this line was then connected to
      the anterior mitral annulus. Pulmonary vein isolation and cavotricuspid isthmus
      ablation were performed in all cases. Ablation was performed using an irrigated
      catheter with the endpoint of achieving complete linear block demonstrated by
      online double potentials, differential pacing techniques, and an activation
      detour. RESULTS: Of 20 patients in AF prior to linear ablation, arrhythmia
      terminated in 12 (60%), including half the patients with chronic AF, during
      ablation. Despite repeated ablation, complete linear block was achieved in only
      14 of 24 patients (58%). Complete linear conduction block resulted in an
      activation detour around the mitral annulus and PVs with a delay of 158 +/- 30 ms
      (P = .0001), significantly delayed activation of the lateral LA with prolongation
      of P-wave duration (P = .002), and characteristic change in P-wave morphology
      during sinus rhythm (P = .002). Of the 14 with anterior LA transection, 4 (29%)
      have had regular atrial tachycardias due to macroreentry through recovered gaps.
      Nine of these 14 (64%) have remained arrhythmia-free without antiarrhythmics
      compared to 3 of 10 (30%) with incomplete block at 28 +/- 4 months following
      their last procedure (P = .2). CONCLUSIONS: This study demonstrates the
      feasibility of catheter ablation to transect the anterior LA in humans. While
      being effective in the termination of AF, this configuration of linear lesions is
      technically challenging to complete, results in significant delayed LA
      activation, and is associated with modest long-term arrhythmia suppression.

PMID- 15851151
TI  - Ablation of atrial fibrillation: are the lines drawn?

PMID- 15851152
TI  - Prospective assessment after pediatric cardiac ablation: recurrence at 1 year
      after initially successful ablation of supraventricular tachycardia.
AB  - OBJECTIVES: A multicenter prospective study was performed to assess the results
      and risks associated with radiofrequency ablation in children. This report
      focuses on recurrences following initially successful ablation. METHODS: Patients
      recruited for the study were aged 0 to 16 years and had supraventricular
      tachycardia due to accessory pathways or atrioventricular nodal reentrant
      tachycardia (AVNRT), excluding patients with more than trivial congenital heart
      disease. A total of 481 patients were recruited into the prospective cohort and
      were followed at 2, 6, and 12 months following ablation. RESULTS: There were 517
      successfully ablated substrates out of 540 attempted (95.7%). Loss to follow-up
      for individual substrates was 3.3%, 10.6%, and 21.2% at 2, 6, and 12 months,
      respectively. Recurrence was observed in 7.0%, 9.2%, and 10.7% of these
      substrates at 2, 6, and 12 months, respectively (adjusted for loss to follow-up
      as an independent source of data censoring). Recurrence rate varied by substrate
      location (24.6% for right septal, 15.8% for right free wall, 9.3% for left free
      wall, and 4.8% for left septal), as well as for AVNRT versus all others (4.8% vs
      12.9%) at 12 months. The recurrence rate was higher for substrates ablated using
      power control but was not a function of whether isoproterenol was used for
      postablation testing. CONCLUSIONS: Recurrence after initially successful ablation
      occurs commonly in children. It is least common after AVNRT ablation and most
      common following ablation of right-sided pathways. These results serve as a
      benchmark for the time course of recurrence following initially successful
      ablation of supraventricular tachycardia in children.

PMID- 15851153
TI  - Mechanisms of recurrent atrial fibrillation after pulmonary vein isolation by
      segmental ostial ablation.
AB  - OBJECTIVES: The aim of this study was to determine the mechanisms responsible for
      recurrent atrial fibrillation (AF) after pulmonary vein isolation (PV) by
      segmental ostial ablation. BACKGROUND: Recovery of conduction into a previously
      isolated PV is a common observation when there is recurrent AF soon after
      segmental ostial ablation. However, the mechanisms of recurrent AF have been
      unclear. METHODS: A repeat ablation procedure was performed in 50 patients who
      had recurrent paroxysmal AF at a mean of 7 +/- 6 months after segmental ostial
      ablation to isolate the PVs. During the repeat procedure, a ring catheter was
      inserted into each PV during sinus rhythm and AF to determine whether the veins
      were still isolated and, if not, whether there were PV tachycardias with a cycle
      length shorter than in the adjacent left atrium during AF. RESULTS: There was
      recovery of conduction over a previously ablated muscle fascicle in >/=1 PV in 49
      patients (98%). There were 10 +/- 2 episodes of PV tachycardia per minute in 36
      (72%) of the 50 patients during AF. Repeat ablation was performed by segmental
      ostial ablation (23 patients) or by left atrial catheter ablation to encircle the
      left- and right-sided PVs 1 to 2 cm from the ostia, with additional ablation
      lines in the posterior left atrium and mitral isthmus (27 patients). At 6-month
      follow-up, among 23 patients who underwent repeat ablation by segmental ostial
      ablation, AF recurred in 4 (21%) of the 19 patients who had PV tachycardias and
      in 3 (75%) of the 4 patients who did not (P = .03). Among the 27 patients who
      underwent left atrial ablation, AF recurred in 2 (12%) of the 17 patients who had
      PV tachycardias and in 1 (10%) of the 10 patients who did not (P = 0.7).
      CONCLUSIONS: Recovery of conduction in previously ablated muscle fascicles is a
      common finding in patients with recurrent AF after segmental ostial ablation. The
      efficacy of repeat segmental ostial ablation depends on the presence of PV
      tachycardias, whereas left atrial ablation is effective regardless of whether PV
      tachycardias are present or not during AF.

PMID- 15851154
TI  - The safety and efficacy of multiple consecutive cryo lesions in canine pulmonary
      veins-left atrial junction.
AB  - OBJECTIVE: The purpose of the study is to evaluate the safety and efficacy of
      multiple cryo lesions in canine pulmonary veins-left atrial junction. BACKGROUND:
      The use of radiofrequency to achieve electrical isolation of the pulmonary veins
      (PVs) has been associated with PV stenosis. No information is currently available
      concerning the safety and the electrophysiological effects of multiple and
      consecutive cryo applications at the PV-left atrial junction. METHODS: Liquid
      N(2)O was delivered into semi-compliant 15 to 22-mm-diameter balloons. In 13 dogs
      weighing 34 +/- 2 kg, one to four consecutive cryo lesions were randomly applied
      to each PV for 3 minutes in 6-minute intervals. The pre- and post-PV sizes were
      recorded by angiography. Electrogram activity and pacing thresholds were recorded
      before and after cryo. PV patency and the PV-atrial tissue characteristics were
      evaluated grossly and histologically. RESULTS: Pacing capture was not possible
      with 10 mA postablation in 26/46 (57%) electrodes, and in 20 (43%) electrodes
      pacing threshold increased from 1.6 +/- 1.7 mA to 7.8 +/- 3.2 mA. The total
      elimination of recorded electrograms was noted in 22%, 29%, and 18% following 1,
      2, and 3 cryo lesions respectively. After 4 lesions this value increased to 53%.
      No significant changes in PV diameter were recorded in any of the veins pre vs
      the terminal study. The PVs and PV-atrial interface tissue were soft, compliant,
      and without collagen or cartilaginous tissue. There was no hemoptysis in any of
      the dogs. CONCLUSION: In this study, cryo balloon technology is effective and
      safe regardless of the number of lesions applied and the freezing temperatures
      achieved. Four consecutive cryo applications result in a significant increase in
      pacing threshold and a decrease in activity of local atrial electrograms.

PMID- 15851155
TI  - Role of sodium and calcium channel block in unmasking the Brugada syndrome.
AB  - OBJECTIVE: We hypothesized that a combination of I(Na) and I(Ca) blockade may be
      more effective in causing loss of the epicardial action potential (AP) dome and
      precipitating the Brugada syndrome (BS). The present study was designed to test
      this hypothesis in an in vitro model of BS. BACKGROUND: The Brugada syndrome is
      characterized by an ST segment elevation in the right precordial ECG leads and a
      high risk of sudden death. The ECG sign of BS is often concealed, but can be
      unmasked with potent sodium channel blockers. Using canine right ventricular (RV)
      wedge preparations, we previously developed an experimental model of BS using
      flecainide to depress the AP dome in RV epicardium. METHODS: Intracellular APs
      and a transmural ECG were simultaneously recorded from canine RV wedge
      preparations. RESULTS: Terfenadine (5-10 microM)-induced block of I(Ca) and I(Na)
      caused heterogeneous loss of the epicardial AP dome, resulting in ST segment
      elevation, phase 2 reentry (12/16), and spontaneous polymorphic VT/VF (6/16).
      Flecainide (</=7.5 microM), ajmaline (</=20 microM), and procainamide (</=300
      microM) failed to generate polymorphic VT in any preparation except when combined
      with a calcium channel blocker (verapamil, </=20 microM). Terfenadine-induced ST
      segment elevation was normalized and arrhythmias suppressed following I(to) block
      with 4-aminopyridine (0.5-2 mM). CONCLUSION: Our data suggest that combined
      sodium and calcium channel block may be more effective than sodium channel block
      alone in unmasking the Brugada syndrome and that pharmacologic agents that
      inhibit I(to) may be useful in preventing lethal arrhythmias in patients with the
      syndrome.

PMID- 15851156
TI  - 2APB- and JTV519(K201)-sensitive micro Ca2+ waves in arrhythmogenic Purkinje
      cells that survive in infarcted canine heart.
AB  - OBJECTIVES/BACKGROUND: Studies from several laboratories have implicated
      intracellular Ca(2+) dynamics in the modulation of electrical activity. We have
      reported that abnormal Ca(2+) wave activity is the underlying cause of
      afterdepolarization-induced electrical activity in subendocardial Purkinje cells
      that survive in the 48-hour infarcted canine heart. These cells form the focus of
      arrhythmias at this time postcoronary artery occlusion. METHODS: We studied the
      effects of agonists and antagonists on the abnormal Ca(2+) release activity of
      Purkinje cell aggregates dispersed from the subendocardium 48 hours postcoronary
      artery occlusion (IZPCs). Studies were completed using epifluorescent microscopy
      of Fluo-3 loaded Purkinje cells. RESULTS: Similar to our previous report, highly
      frequent traveling micro Ca(2+) transients (muCaiTs) and cell-wide Ca(2+) waves
      were seen in IZPCs in the absence of any drug. Isoproterenol (ISO) increased
      muCaiTs and cell-wide Ca(2+) waves in Purkinje cells dispersed from the normal
      heart (NZPCs). In IZPCs, ISO increased cell-wide wave frequency but had no effect
      on the already highly frequent micro Ca(2+) wave transient activity, suggesting
      that ISO lowers the threshold of cell-wide generators responding to micro Ca(2+)
      transients. Drugs that block inward sodium or calcium currents (verapamil,
      tetrodotoxin) had no effect on Ca(2+) activity in Purkinje cells. Antagonists of
      intracellular Ca(2+) release channels [ryanodine, JTV519(K201)] greatly
      suppressed spontaneous Ca(2+) release events in IZPCs. 2APB, an agent that blocks
      IP(3) receptors, greatly reduced the frequency of Ca(2+) events in IZPCs.
      CONCLUSIONS: In arrhythmogenic Purkinje cells that survive in the infarcted
      heart, agents that block or inhibit intracellular Ca(2+) release channel activity
      reduced Ca(2+) waves and could be antiarrhythmic.

PMID- 15851157
TI  - Loss of electrical communication, but not plaque formation, after mutations in
      the cytoplasmic loop of connexin43.
AB  - OBJECTIVES: The aim of this study was to determine if the structural integrity of
      a region in the cytoplasmic loop (amino acids 119-144; region "L2") of connexin43
      (Cx43) is necessary to maintain normal channel function. BACKGROUND: Cx43 is the
      most abundant gap junction protein in the heart. The ability of these channels to
      close under pathologic conditions such as ischemia may be a key substrate for
      cardiac arrhythmias. Previous studies have shown that Cx43 regulation involves
      the intramolecular interaction of its carboxyl terminal domain (a "gating
      particle") with a separate region of the molecule acting as a receptor. We
      recently proposed that a region in the cytoplasmic loop of Cx43 (amino acids 119
      144; region "L2") might function as a receptor. METHODS: Using site-directed
      mutagenesis and patch clamp analysis, as well as fluorescent microscopy, we
      examined gap junction plaque formation and channel properties of Cx43 L2 mutants.
      RESULTS: Deletions of 5 to 6 amino acids within the L2 domain interfered with the
      formation of functional gap junction channels, although gap junction plaques were
      clearly visible. Selected point mutations in the region (including those present
      in patients with oculodentodigital dysplasia) caused modifications ranging from
      complete channel closure to changes in unitary conductance. CONCLUSIONS: These
      results show that the L2 region is essential for maintenance of the normal
      architecture of the channel pore. This information is consistent with the notion
      that the L2 region could be a receptor for the carboxy terminal domain; the
      latter interaction would lead to channel closure under conditions such as
      myocardial ischemia and infarction.

PMID- 15851158
TI  - The clinical relevance of connexin gating: how to control communication in the
      heart.

PMID- 15851160
TI  - Polymorphic ventricular tachycardia associated with mutations in KCNJ2.

PMID- 15851159
TI  - Polymorphic ventricular tachycardia and KCNJ2 mutations.
AB  - We sought to identify the electrophysiologic basis of life-threatening events
      associated with polymorphic ventricular tachycardia (PVT) in young patients with
      heterozygous KCNJ2 mutations. PVT describes a beat-to-beat alternating QRS axis
      and morphology during ventricular tachycardia. PVT may be well tolerated and even
      asymptomatic in young patients without other heart disease, but an association
      with syncope, cardiac arrest, or sudden death has long been known. Little is
      known of the basis of life-threatening events associated with PVT in this
      setting. We identified heterozygous KCNJ2 mutations (R67W and C101R respectively)
      in 2 adolescents with PVT (cycle length > 375 ms, < 160 beats/minute).
      Biophysical properties of wild-type and mutant KCNJ2 channels were characterized
      during heterologous expression in Xenopus oocytes. Despite a large tachycardia
      burden, neither patient experienced symptoms during electrocardiographic
      documentation of PVT. One patient had a history of cardiac arrest, but neither
      had other evidence of heart disease. Both patients were treated with an
      implantable cardioverter-defibrillator (ICD). In one patient, ICD interrogation
      identified rapid ventricular tachycardia (cycle length of 190 to 270 ms),
      terminated with a single 29-J asynchronous shock, as the cause of 2 syncopal
      episodes occurring 19 months apart. Biophysical characterization of KCNJ2-C101R
      demonstrated a loss-of-function and a dominant-negative effect on Kir2.1. Similar
      effects were previously observed for KCNJ2-R67W. Heterozygous mutations in KCNJ2
      can cause life-threatening ventricular arrhythmias. Arrhythmia documented during
      cardiac arrest is rapid ventricular tachycardia; ICD is effective therapy for
      cardiac arrest in patients with PVT due to KCNJ2 mutation.

PMID- 15851161
TI  - Advances in antiarrhythmic drug treatment of atrial fibrillation: where do we
      stand now?

PMID- 15851162
TI  - Long RP interval tachycardia: what is the mechanism?

PMID- 15851163
TI  - Visualization of remnants of the left atrial appendage following epicardial
      surgical removal.

PMID- 15851164
TI  - Clinical considerations for the allied professional: standards of professional
      practice for the allied professional in electrophysiology and pacing.

PMID- 15851165
TI  - Trends in treated ventricular fibrillation out-of-hospital cardiac arrest: a 17
      year population-based study.
AB  - OBJECTIVES: The aims of this study were to describe the trends of ventricular
      fibrillation (VF) out-of-hospital cardiac arrest in Rochester, Minnesota, since
      1985 and to determine coexistent trends in implantable cardioverter defibrillator
      (ICD) placement and termination of potentially lethal ventricular arrhythmias
      that might explain, at least in part, a declining incidence trend. BACKGROUND:
      The incidence of VF out-of-hospital cardiac arrest treated by emergency medical
      services (EMS) personnel has declined over the past decade. Because VF out-of
      hospital cardiac arrest occurs primarily in the setting of severe coronary artery
      disease, primary and secondary prevention strategies may account in part for the
      decline. In particular, ICD use in large primary and secondary prevention
      clinical trials in patients at high risk of sudden death has demonstrated that
      these devices improve survival. METHODS: All residents of the City of Rochester,
      Minnesota, who presented with a VF out-of-hospital cardiac arrest from 1985 to
      2002, identified and treated by EMS, were included in the study. In addition,
      residents of the City of Rochester who received their first ICD implant from 1989
      to 2002 were identified. From the ICD records, general demographics, etiology of
      heart disease, comorbid medical disease, and indication for ICD placement were
      abstracted. Follow-up data obtained from this population included ICD shocks, the
      underlying rhythm disturbance, and death. RESULTS: The overall incidence of EMS
      treated VF out-of-hospital cardiac arrest in Rochester during the study period
      was 17.1 per 100,000 [95% confidence interval (CI) 15.1-19.4]. The incidence has
      decreased significantly (P < 0.001) over the study period: 1985-1989:
      26.3/100,000 (95% CI 21.0-32.6), 1990-1994: 18.2/100,000 (95% CI 14.1-23.1), 1995
      1999: 13.8/100,000 (95% CI 10.4-17.9), 2000-2002: 7.7/100,000 (95% CI 4.7-11.9).
      One hundred ten patients received an ICD. The placement of ICDs also has
      increased dramatically over the past 10 years: 1990-1994: 5.0/100,000 to 2000
      2002: 20.7/100,000 (P < 0.001). ICDs terminated VF or fast ventricular
      tachycardia (<270 ms) in 22 patients. Termination of these potentially fatal
      arrhythmias has shown a trend toward an increase over the study period: 1990
      1994: 1.1/100,000 to 2000-2002: 3.5/100,000 (P = 0.06). CONCLUSIONS: The
      incidence of VF out-of-hospital cardiac arrest is declining. In contrast, the
      rates of ICD placement and ICD termination of ventricular tachycardia or VF are
      markedly increasing. Sudden death preventive strategies are multifactorial. These
      observations suggest that ICD termination of potentially lethal ventricular
      arrhythmias may contribute to the lower incidence of VF out-of-hospital cardiac
      arrest.

PMID- 15851166
TI  - Have increasing rates of defibrillator implantation reduced the incidence of out
      of-hospital cardiac arrest?

PMID- 15851167
TI  - Favorable effect of pulmonic vein isolation by partial circumferential ablation
      on ostial flow velocity.
AB  - OBJECTIVES: The aim of this study was to determine the effect of electrical
      isolation of pulmonic vein (PV) on flow velocity. BACKGROUND: We report our
      experience with electrical isolation of PV by partial circumferential ablation
      and its effect on ostial peak flow velocity as assessed by phased-array
      ultrasound catheter imaging. METHODS: Sixty-two patients participated in the
      study. Magnetic electroanatomic mapping, ultrasound catheter imaging, and Lasso
      mapping catheter were used. Electrical isolation was achieved by delivering
      radiofrequency ablation (RFA) lesions proximal to Lasso mapping catheter bipoles
      showing PV entry. Following this, the number of RFA lesions/PV and their segment
      wise distribution (maximum 4/PV) were assessed. RESULTS: Fifty right superior, 51
      left superior, 32 left inferior, and 17 right inferior PVs were isolated. RFA
      involved 4 segments in 42 PVs, 3 segments in 61 PVs, and </=2 segments in 47 PVs.
      Electrical isolation augmented ostial peak flow velocity (55 +/- 15 cm/s to 96 +/
      26 cm/s). This net increase was higher for superior versus inferior PVs (43 +/-
      23 cm/s and 34 +/- 18 cm/s; P = .02). For </=2, 3, and 4 segments ablated per
      vein, the net increase in peak flow velocity was 33 +/- 22 cm/s, 42 +/- 23 cm/s,
      and 46 +/- 23 cm/s, respectively (P = .02). Over a mean follow-up of 16 +/- 7
      months, freedom from atrial fibrillation (AF) or >90% reduction in AF burden,
      either with or without previously ineffective antiarrhythmic agents, was achieved
      in 54 patients (87%). CONCLUSIONS: In the majority of PVs (72%), electrical
      isolation can be achieved by partial circumferential ablation (targeting </=3
      segments/PV) with lower acute increase in ostial peak flow velocity and good AF
      control.

PMID- 15851168
TI  - Irrigated-tip catheter ablation of intraatrial reentrant tachycardia in patients
      late after surgery of congenital heart disease.
AB  - OBJECTIVES: The aim of this study was to evaluate irrigated-tip catheter for
      ablation of intraatrial reentrant tachycardias late after surgical repair of
      congenital heart disease. BACKGROUND: In congenital heart disease patients, the
      right atrium can be markedly enlarged with areas of low blood flow.
      Radiofrequency (RF) lesion creation may be hampered by insufficient electrode
      cooling at sites with low blood flow. METHODS: Thirty-six consecutive patients
      with intraatrial reentrant tachycardia refractory to antiarrhythmic therapy from
      two centers were included in the study. Entrainment pacing and electroanatomic
      mapping (CARTO) were used to delineate reentrant circuits and critical isthmus
      sites. RF ablation was performed using an irrigated-tip catheter (Navistar
      Thermocool). RESULTS: Fifty-two intraatrial reentrant tachycardia circuits were
      identified, and 48 were targeted with RF ablation. RF ablation was performed
      using a mean of 13 +/- 11 irrigated RF applications per tachycardia isthmus with
      a mean power of 36 +/- 8 W. In a historical control group of congenital heart
      disease patients managed with conventional catheter ablation, the number of
      lesions per isthmus was higher (23 +/- 11) and mean power was lower (27 +/- 14
      W). Acute success was achieved in 45 intraatrial reentrant tachycardias (94% of
      targeted tachycardias and 87% of all tachycardias). After a mean follow-up of 17
      +/- 7 months, 33 (92%) of 36 patients were free of recurrence. Five patients
      (14%) developed paroxysmal atrial fibrillation. CONCLUSIONS: The combination of
      modern techniques including electroanatomic mapping and catheter irrigation
      allows safe and highly effective ablation of intraatrial reentrant tachycardia in
      patients with surgically repaired congenital heart disease.

PMID- 15851169
TI  - Diagnostic value of epinephrine test for genotyping LQT1, LQT2, and LQT3 forms of
      congenital long QT syndrome.
AB  - OBJECTIVES: The aim of this study was to test the hypothesis that epinephrine
      test may have diagnostic value for genotyping LQT1, LQT2, and LQT3 forms of
      congenital long QT syndrome (LQTS). BACKGROUND: A differential response of
      dynamic QT interval to epinephrine infusion between LQT1, LQT2, and LQT3
      syndromes has been reported, indicating the potential diagnostic value of the
      epinephrine test for genotyping the three forms. METHODS: The responses of 12
      lead ECG parameters to epinephrine were retrospectively examined in 15 LQT1, 10
      LQT2, 8 LQT3, and 10 healthy volunteers to select the best ECG criteria for
      separating the four groups. The epinephrine test then was prospectively conducted
      in 42 probands clinically affected with LQTS, their 67 family members, and 10 new
      volunteers. The best criteria were applied in a blinded fashion to prospectively
      separate a different group of 31 LQT1, 23 LQT2, 6 LQT3, and 30 Control patients
      (10 genotype-negative LQT1, 10 genotype-negative LQT2 family members, and 10
      volunteers). RESULTS: The sensitivity (penetrance) by ECG diagnostic criteria was
      lower in LQT1 (68%) than in LQT2 (83%) or LQT3 (83%) before epinephrine and was
      improved with steady-state epinephrine in LQT1 (87%) and LQT2 (91%) but not in
      LQT3 (83%), without the expense of specificity (100%). The sensitivity and
      specificity to differentiate LQT1 from LQT2 were 97% and 96%, those from LQT3
      were 97% and 100%, and those from Control were 97% and 100%, respectively, when
      Delta mean corrected Q-Tend >/=35 ms at steady state was used. The sensitivity
      and specificity to differentiate LQT2 from LQT3 or Control were 100% and 100%,
      respectively, when Delta mean corrected Q-Tend >/=80 ms at peak was used.
      CONCLUSIONS: Epinephrine infusion is a powerful test to predict the genotype of
      LQT1, LQT2, and LQT3 syndromes as well as to improve the clinical diagnosis of
      genotype-positive patients, especially those with LQT1 syndrome.

PMID- 15851170
TI  - Historical vignette: The long QT syndrome and the sympathetic nerves.

PMID- 15851171
TI  - T wave morphology analysis distinguishes between KvLQT1 and HERG mutations in
      long QT syndrome.
AB  - OBJECTIVES: The aim of this study was to develop an objective method to
      distinguish between HERG and KvLQT1 genotypes on the surface ECG. BACKGROUND: The
      two most prevalent genes affected in long QT syndrome (LQTS) are KvLQT1 (KCNQ1)
      and HERG (KCNH2), which are mutated in >90% of patients with a reported LQTS
      genotype. It is known that T waves have lower amplitude and more notches in HERG
      patients than T waves in KvLQT1 patients, but this semiquantitative method lacks
      the discriminative power to be used in a clinical setting. We developed a simple
      mathematical method that allowed us to quantify T wave shape in LQTS mutations
      for clinical use. METHODS: ECGs from 24 HERG patients, 13 KvLQT1 LQTS patients,
      and 13 healthy relatives were examined. The repolarizing integral (RI) was
      constructed from the T wave. The resulting RI is sigmoid and was modeled using
      the Hill equation as (RI(t) = V(max)*[t(n)/[K(m)(n) + t(n)]]). V(max) is
      equivalent to the total T wave area, K(m) is the time when 50% of the T wave area
      is reached, and n is a measure of the slope of the sigmoid RI. RESULTS: The RI
      correlated nearly perfectly to the fitted sigmoid, r = 0.99. In lead V(2), V(max)
      was larger in KvLQT1 (0.148 +/- 0.021) (mean +/- SE) compared to HERG (0.080 +/-
      0.012) and controls (0.067 +/- 0.021). The Hill coefficient n of the RI
      discriminated perfectly between HERG (2.00 +/- 0.11) and KvLQT1 (4.11 +/- 0.15).
      CONCLUSIONS: RI allows distinguishing between HERG and KvLQT1 mutations based
      solely on the T wave morphology in the present LQTS population.

PMID- 15851172
TI  - Quantifying T wave morphology in the digital era.

PMID- 15851173
TI  - Biventricular pacing reduces the induction of monomorphic ventricular
      tachycardia: a potential mechanism for arrhythmia suppression.
AB  - OBJECTIVES: The aim of the present study was to evaluate in a prospective
      randomized fashion the electrophysiologic effects of acute biventricular (BV)
      pacing. We hypothesized that (1) the local coupling interval in the left
      ventricle in response to right-sided ventricular premature beats is prolonged
      when BV pacing is applied during the drive train compared with right ventricular
      (RV) pacing, and (2) BV programmed electrical stimulation (PES) decreases the
      induction of ventricular arrhythmias compared with standard RV-PES, regardless of
      the presence of intraventricular conduction delay. BACKGROUND: Previous studies
      have suggested that BV pacing might decrease the frequency of ventricular
      arrhythmias; however, the mechanism of arrhythmia suppression remains unclear.
      METHODS: Eighteen patients with coronary artery disease were randomized to RV-PES
      or BV-PES with a repeat study using the other pacing mode. The RV effective
      refractory periods were measured during RV-PES and BV-PES. In addition, the local
      LV S(1)-S(2) coupling interval was measured at 600/450 ms and 400/350 ms during
      RV-PES and BV-PES. RESULTS: BV-PES had no effect on RV effective refractory
      periods. On the other hand, the local LV S(1)-S(2) coupling intervals increased
      significantly during BV-PES compared with RV-PES (P < .0001). Ventricular
      tachycardia was induced in six patients using RV-PES but in only one patient with
      BV-PES (RR = 83%, P = .01). No difference was observed in the induction of
      ventricular fibrillation. CONCLUSIONS: BV-PES significantly reduced the induction
      of ventricular tachycardia compared to RV-PES, with no significant effect on
      ventricular fibrillation induction. Our findings may help explain the reduced
      incidence of ventricular arrhythmias noted with chronic BV pacing.

PMID- 15851174
TI  - Radiofrequency catheter ablation of ventricular tachycardia in children and young
      adults with congenital heart disease.
AB  - OBJECTIVES: The aim of this study was to expand data on outcomes for
      radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in young
      patients and to identify obstacles to success. BACKGROUND: Ablation of VT is
      performed infrequently in young patients. Published experience has been limited
      to case reports and small descriptive series. METHODS: A retrospective review of
      97 consecutive VT ablation procedures involving 62 patients at a single
      institution from 1990 to 2003 was undertaken. All intention-to-treat procedures
      were analyzed. RESULTS: Mean age was 13.9 +/- 9.4 years. Procedures were
      categorized according to VT mechanism as follows: idiopathic right ventricle (n =
      37); idiopathic left ventricle (n = 24); congenital heart disease (n = 20); or
      other structural disease (n = 16). Acute success was achieved in 58 (60%) of 97
      procedures. Of the 39 failures, 33 were aborted cases due to inability to induce
      sufficient ectopy for mapping in 12, high-risk location near the His bundle or
      coronary artery in 11, unstable VT in 7, and anatomic obstacles in 3. Recurrence
      rate after acutely successful RFCA was 34% (20/58 procedures) at a mean follow-up
      of 3.8 +/- 2.0 years. Ultimately, long-term success was achieved in 38 (61%) of
      62 patients after a mean of 1.6 +/- 0.9 procedures, with the highest success rate
      (87%) for idiopathic left ventricular tachycardia. CONCLUSIONS: When analyzed on
      a strict intention-to-treat basis, a long-term success rate of 61% is observed
      with ablation of VT in young patients. Inability to induce stable VT for
      precision mapping and certain high-risk VT locations can be significant obstacles
      to success.

PMID- 15851175
TI  - Intention to treat: To the heart of the matter for young patients with
      ventricular tachycardia.

PMID- 15851176
TI  - Percutaneous epicardial mapping during ablation of difficult accessory pathways
      as an alternative to cardiac surgery.
AB  - OBJECTIVES: The aim of this study was to define the role of percutaneous
      epicardial mapping for the ablation of previous failed ablation of accessory
      pathways. BACKGROUND: Cardiac surgery is the only curative option for failed
      radiofrequency (RF) catheter ablation of accessory pathway (AP)-mediated
      tachycardias. We investigated a combined percutaneous epicardial and endocardial
      approach for failed AP ablations. METHODS: We present our experience in a series
      of 6 cases (7 APs) with previous failed attempts at catheter ablation (median 2
      attempts, range 1-4) and persistent symptomatic tachycardias. Endocardial mapping
      of the APs was performed using conventional techniques. Sites with local
      electrograms suggestive of AP location were selected. When initial endocardial
      mapping was not successful for ablation of the pathway, percutaneous
      transthoracic pericardial puncture was performed via a subxiphoid approach, and
      an ablation catheter was positioned at the epicardial aspect of the putative AP
      location for epicardial-endocardial electrogram comparison. Endocardial RF energy
      was applied to locations considered appropriate. Epicardial RF applications were
      delivered when endocardial applications failed. Coronary arteriography was
      performed to assess the proximity of coronary arteries to the ablation catheter.
      RESULTS: APs were located in the right free wall (4 patients, 5 APs) and the
      right (1 patient) and left (1 patient) posteroseptal regions. In all patients,
      epicardial mapping assisted in identifying successful ablation sites. In 3
      patients, the earliest atrial activation during orthodromic tachycardia was
      present in an epicardial electrogram. Successful AP ablation was achieved with an
      epicardial RF application in 2 patients, either alone or with simultaneous
      endocardial-epicardial delivery. In the remaining 4 patients, APs were
      successfully ablated endocardially after epicardial mapping. These patients
      represent 18% of all cases referred to our institution for ablation of previously
      failed accessory pathways (6/32 patients). CONCLUSIONS: A combined endocardial
      epicardial approach to mapping and RF ablation can facilitate successful
      endocardial ablation in most cases. In selected cases, APs can be ablated by
      epicardial delivery of RF. Epicardial mapping is an effective alternative to
      cardiac surgery for patients in whom prior attempts at AP ablation have failed.

PMID- 15851177
TI  - T vector and loop characteristics in coronary artery disease and during acute
      ischemia.
AB  - OBJECTIVE: Three-dimensional characterization of the ventricular repolarization
      by the T vector and T vector loop morphology in coronary artery disease (CAD),
      and their response to short-term (no flow) ischemia induced by coronary occlusion
      during a percutaneous intervention (PCI). BACKGROUND: The risk for sudden cardiac
      death is increased in conditions of acute or permanently heterogeneous
      ventricular repolarization, for which ischemia is a risk factor. METHODS: Fifty
      six CAD patients without visible collateral circulation were studied during an
      elective single-vessel PCI, and 10 healthy controls twice at rest. T vector
      parameters (Televation, Tazimuth, and QRS-T angle), and T loop parameters (Tarea,
      Tavplan, and Teigenv) were measured by vectorcardiography. ST vector magnitude
      (ST-VM) and its change (STC-VM) were used for reference. RESULTS: At rest, T
      vector loop morphology (Tarea, Teigenv) was significantly different in CAD
      patients and controls, while T vector angles did not separate the groups.
      Ischemia induced significant changes in T loop parameters in the entire CAD
      group, whereas in the LAD subgroup significant changes were seen also in T vector
      angle. The T loop morphology was significantly different at baseline and a more
      pronounced response to ischemia (Tarea) was seen in patients with, than in those
      without, a history of hypertension. CONCLUSION: T loop morphology, rather than
      the T vector angle, separated CAD patients from healthy controls. Coronary
      occlusion had significant impact on ventricular repolarization, as assessed by T
      vector and morphology analysis, and most prominently in the LAD group.
      Hypertensive patients appeared especially vulnerable to ischemia.

PMID- 15851178
TI  - Segmental pulmonary vein isolation versus the circumferential approach: is the
      tide turning?

PMID- 15851179
TI  - Ablation with an internally irrigated radiofrequency catheter: learning how to
      avoid steam pops.
AB  - OBJECTIVES: The aim of this study was to assess the feasibility of using
      electrode temperature, impedance, and power to predict and thereby potentially
      prevent steam pops during cooled radiofrequency (RF) ablation. BACKGROUND: When
      myocardial temperature reaches 100 degrees C during RF catheter ablation, steam
      explosions are seen. Saline-cooled RF ablation reduces temperatures at the
      electrode-tissue interface, but excessive intramyocardial heating still may
      occur. METHODS: In anesthetized swine, 26 cooled RF applications were made in the
      right and left atria while observing with intracardiac echocardiography (ICE).
      Power delivery was increased gradually until a steam explosion was seen or a
      maximum output of 50 W was reached. RESULTS: ICE identified steam explosions in
      21 RF applications. Steam explosions were associated with a large impedance
      increase, >25 Omega in only three cases, whereas small increases <10 Omega (mean
      5.3 +/- 2.6 Omega) occurred in 18 cases. Mean electrode temperature at the time
      of steam explosion was 43.6 degrees C +/- 5.3; 18 of 21 explosions occurred when
      temperature reached >/=40 degrees C. Mean power and impedance drop were similar
      for applications with and without steam explosions. Five steam explosions were
      associated with a sudden drop in electrode temperature. CONCLUSIONS: Steam
      explosions are common when cooled electrode temperature exceeds 40 degrees C and
      are not predictable from power or impedance drop. Small impedance rises and
      sudden drops in measured electrode temperature indicate possible steam formation.
      Maintaining cooled electrode temperature <40 degrees C during RF likely will
      reduce the risk of steam explosions.

PMID- 15851180
TI  - The effect of vagally induced dispersion of action potential duration on atrial
      arrhythmogenesis.
AB  - OBJECTIVE: The purpose of this study is to ascertain the effects of spatially
      variable ACh distributions on arrhythmogenesis in a morphologically realistic
      computer model of canine atria. BACKGROUND: Vagal stimulation releases
      acetylcholine (ACh), which causes a dose-dependent reduction in action potential
      duration (APD) in the atria. Due to the nonuniform distribution of nerve endings,
      APD dispersion may result, which has been shown to play a role in the breakup of
      activity. METHODS: Reentry was initiated in a computationally efficient,
      morphologically realistic computer model of the atria. Discrete regions
      corresponding to ACh release sites, referred to as islands, were assigned
      shortened APDs in an ACh-dependent fashion. Island APD was varied as well as the
      basal APD. The window of vulnerability for ectopic beat-induction of sustained
      reentry was determined for both left atrial(LA) and right atrial (RA)
      stimulation. The resulting reentries were categorized based on type and location.
      RESULTS: 1) Atrial geometry severely restricts the formation of reentrant
      circuits. 2) Wave fractionation only occurred for large differences between
      island and basal APD. 3) Small ACh concentration differences produced stable
      figure-of-8 reentrant patterns. 4) Large islands displayed more wave breakup but
      could sometimes anchor reentries. CONCLUSIONS: Large APD gradients produced by
      ACh heterogeneity can lead to a breakdown of organized activity.

PMID- 15851181
TI  - Paradoxical undersensing due to quiet timer blanking.
AB  - A case of undersensing of atrial activity by a dual chamber pacemaker is
      presented. Programming to more sensitive voltages exacerbated undersensing, and
      programming to less sensitive levels resolved the undersensing. The mechanism by
      which pacemaker sense amplifiers function to create apparent paradoxical
      undersensing is reviewed.

PMID- 15851182
TI  - Recurrent ventricular fibrillation secondary to aortic valve tumor.
AB  - The case of a patient with recurrent ventricular fibrillation secondary to an
      aortic tumor is reported. Ventricular fibrillation occurs secondary to ischemia,
      arrhythmia, or congenital disease, or it may be an idiopathic event. Irreversible
      and recurrent situations require placement of an implantable cardioverter
      defibrillator (ICD). A patient with recurrent syncope secondary to documented
      ventricular fibrillation without a clear mechanism and a negative
      electrophysiologic study underwent ICD placement. A cardiac papillary
      fibroelastoma at the aortic valve subsequently was found. Cardiac tumors in the
      aortic valve can obstruct the coronary arteries, secondarily causing ischemia and
      ventricular fibrillation. Such a mechanism must be considered in the differential
      diagnosis of sudden death.

PMID- 15851183
TI  - A 25-year control of idiopathic ventricular fibrillation with electrophysiologic
      guided antiarrhythmic drug therapy.
AB  - The case of a 28-year-old man with recurrent syncope and multiple documented
      episodes of idiopathic ventricular fibrillation is reported. Recurrent syncope
      suggesting a self-terminating ventricular tachyarrhythmia occurred after 1 month
      of amiodarone therapy, and ventricular fibrillation was inducible at
      electrophysiologic study. After addition of quinidine, no significant ventricular
      arrhythmias could be induced. Similar results were found during a repeat
      electrophysiologic study performed 23.5 years later. During a 25-year period, the
      patient has remained arrhythmia-free on combined antiarrhythmic medication with
      quinidine and amiodarone.

PMID- 15851184
TI  - Cardiac resynchronization therapy in congestive heart failure: Ready for prime
      time?
AB  - OBJECTIVES/BACKGROUND: The aim of this article is to critically review the data
      accumulated to date on the application of cardiac resynchronization therapy (CRT)
      via biventricular pacing techniques to manage patients with advanced heart
      failure. The data from studies evaluating the effects of long-term right
      ventricular (RV) pacing are also briefly reviewed. METHODS: MEDLINE and selective
      journal searches of English-language reports and a search of references of
      relevant papers were conducted. RESULTS: Cardiac dyssynchrony as reflected by a
      prolonged QRS complex, often in the form of left bundle branch block, is
      encountered in about 30% of patients with moderate-to-advanced heart failure.
      Among these patients, 10% to 15% are candidates for CRT via biventricular pacing.
      Accumulated evidence from randomized controlled studies over the last few years
      has indicated a significant hemodynamic and clinical improvement conferred by CRT
      to class III or IV heart failure patients with idiopathic or ischemic dilated
      cardiomyopathy having a low left ventricular ejection fraction (</=35%) and a
      wide QRS complex (>/=120-150 ms). Newer data suggest a significant reduction in
      overall mortality and heart failure hospitalization, particularly when CRT is
      combined with automatic defibrillator backup. Technical advances with
      percutaneous methods accessing the tributaries of the cardiac veins have raised
      the success rate of implantation of left ventricular leads to >90%. Further
      confirmation from ongoing trials is awaited, and more data from cost
      effectiveness studies are needed before CRT is considered for prime time therapy
      in the heart failure population. If the data confirm a survival benefit from CRT,
      use of this electrical therapy at earlier stages of heart failure might be
      contemplated. New evidence from recent studies suggests a deleterious effect of
      the long-standing practice of producing an iatrogenic left bundle branch block by
      conventional RV apical pacing in patients receiving permanent pacemakers. Thus,
      having already become poignantly aware of the harmful effects of spontaneous left
      bundle branch block, this emerging new evidence about RV apical pacing would
      dictate a change of attitude and direct our attention to alternate sites of
      pacing, such as the left ventricle and/or the RV outflow tract, if not for all
      patients then at least for those with left ventricular dysfunction. CONCLUSIONS:
      CRT offers hemodynamic and clinical improvement to patients with moderate-to
      advanced heart failure, and it might significantly prolong survival in selected
      patients, particularly if devices with defibrillation backup are used. Further
      confirmatory data from randomized mortality trials are needed, and issues of cost
      efficacy must be resolved before this vital therapeutic alternative is ready for
      prime time therapy of heart failure patients.

PMID- 15851185
TI  - Alternation of QRS width and cycle length during a long RP' tachycardia: what is
      the mechanism?

PMID- 15851186
TI  - Intrahisian block with Wenckebach phenomenon.

PMID- 15851187
TI  - Clinical competency statement: Training pathways for implantation of cardioverter
      defibrillators and cardiac resynchronization devices.

PMID- 15851188
TI  - Alternate training track for ICD and CRT implantation for non
      electrophysiologists: are the guidelines too strict to be practical or too simple
      to protect patient care?

PMID- 15851189
TI  - Influence of age and gender on the mechanism of supraventricular tachycardia.
AB  - OBJECTIVES: The objective of this study was to determine the impact of age and
      gender on the mechanism of paroxysmal supraventricular tachycardia (PSVT).
      BACKGROUND: Previous studies have indicated that PSVT mechanism may be influenced
      by age and gender, but contemporary data are limited. METHODS: In 1,754 patients
      undergoing catheter ablation of 1,856 PSVTs between 1991 and 2003, the mechanism
      was classified as atrioventricular reentrant tachycardia (AVRT), atrioventricular
      nodal reentrant tachycardia (AVNRT), or atrial tachycardia (AT). Patients with
      inappropriate sinus tachycardia, atrial flutter, atrial fibrillation, and age <5
      years were excluded. RESULTS: The mean age was 45 +/- 19 years (range 5-96), and
      the majority were women (62%). Overall, AVNRT was the predominant mechanism (n =
      1,042 [56%]), followed by AVRT (n = 500 [27%]) and AT (n = 315 [17%]). There was
      a strong relationship between age and PSVT mechanism; the proportion of AVRT in
      both sexes decreased with age, whereas AVNRT and AT increased (PM < .001 by
      ANOVA). The majority of patients with AVRT were men (273/500 [54.6%]), whereas
      the majority of patients with AVNRT and AT were women (727/1,042 [70%] and
      195/315 [62%], respectively). The distribution of PSVT mechanism was
      significantly influenced by gender (P < .001). In women, 63% had AVNRT, 20% had
      AVRT, and 17.0% had AT. In men, 45% had AVNRT, 39% had AVRT, and 17% had AT.
      AVNRT replaced AVRT as the dominant PSVT mechanism at age 40 in men and at age 10
      in women. CONCLUSIONS: The mechanism of PSVT in patients presenting for ablation
      is significantly influenced by both age and gender.

PMID- 15851190
TI  - Age, gender, and supraventricular arrhythmias: roles of ion channels, connexins,
      and tissue architecture?

PMID- 15851191
TI  - Deaths associated with implantable cardioverter defibrillator failure and
      deactivation reported in the United States Food and Drug Administration
      Manufacturer and User Facility Device Experience Database.
AB  - OBJECTIVES: The aim of this study was to understand the causes of implantable
      cardioverter defibrillator (ICD) failure and complications so that adverse
      events, including unnecessary death, can be prevented. BACKGROUND: Sudden death
      may occur if an ICD fails to treat life-threatening ventricular arrhythmias.
      METHODS: The United States Food and Drug Administration Manufacturer and User
      Facility Device Experience Database was searched for ICD devices and the search
      term "death." The search yielded 212 death events involving 100 ICD pulse
      generator and lead models from five manufacturers. These death events were
      associated with (A) ICD devices for which pulse generator interrogation data
      and/or the results of the manufacturers analysis of returned devices were
      available; (B) ICD devices for which neither interrogation data nor the results
      of the manufacturer's analysis were reported; and (C) normally functioning ICDs
      that had been deactivated. RESULTS: (A) A total of 103 (69%) of 150 death events
      were associated with defective pulse generators or high-voltage leads. Most
      (34/42 [81%]) apparently sudden or arrhythmic death events were associated with
      high-voltage lead failure; other deaths were related to pulse generator failure
      (8/42 [19%]) caused by electronic component defects. (B) A total of 21 of 51
      death events were related to a manufacturer's recall; all deaths were arrhythmic
      but without allegation of device failure. (C) Eleven death events occurred in
      patients whose pulse generators were found to be off or deactivated; these
      devices appeared to have been deactivated accidentally or by exposure to magnetic
      fields, or they were not reactivated after elective surgery. CONCLUSIONS: ICD
      device failure and unintended pulse generator deactivation have resulted in
      unnecessary deaths. Although these deaths may be infrequent, improved devices and
      follow-up techniques are needed. The magnet deactivation feature probably is
      unsafe, and health professionals and patients should be cautioned.

PMID- 15851192
TI  - Electrocardiogram during tachycardia in patients with anterograde conduction over
      a Mahaim fiber: old criteria revisited.
AB  - OBJECTIVES: The aim of this study was to prospectively evaluate the sensitivity,
      specificity, and positive and negative predictive values of previously described
      ECG criteria to identify preexcited tachycardia due to decrementally conducting
      accessory pathways (QRS axis between 0 and -75 degrees , QRS width < or = 0.15
      seconds, an R wave in lead I, an rS pattern in lead V(1), RS > 1 QRS transition >
      V(4), and cycle length between 220 and 450 ms). BACKGROUND: Preexcited
      tachycardia associated with decrementally conducting right-sided accessory
      pathways usually shows a rather "narrow" QRS complex and can be difficult to
      differentiate from supraventricular tachycardia (SVT) with left bundle branch
      block (LBBB) aberrant conduction. METHODS: We analyzed three groups of patients:
      32 patients with an atriofascicular pathway (group I); 8 patients with long (n =
      3) or short (n = 5) decrementally conducting right-sided AV pathway (group II);
      and a control group that consisted of 35 patients with SVT and LBBB (group III).
      RESULTS: Presence of all six criteria had 87.5% sensitivity in group I and a 0%
      sensitivity in group II. There were four false negatives in group I. The negative
      predictive value was 82.5%, with six false positives in group III (five patients
      with an aberrant LBBB-shaped tachycardia with ventriculoatrial conduction over an
      accessory AV pathway). The criterion cycle length was not helpful. CONCLUSIONS:
      Criteria for identifying a tachycardia with anterograde conduction over a Mahaim
      fiber are helpful only in atriofascicular pathways, with a sensitivity of 87.5%
      and a negative predictive value of 82.5%. The major cause of false positives was
      a tachycardia with aberrant LBBB conduction and ventriculoatrial conduction over
      an accessory AV pathway.

PMID- 15851193
TI  - Ventricular high-rate episodes in pacemaker diagnostics identify a high-risk
      subgroup of patients with tachy-brady syndrome.
AB  - OBJECTIVES: The purpose of this study was to evaluate the frequency and clinical
      significance of ventricular high-rate (VHR) episodes (ventricular rate >162 bpm)
      in patients with symptomatic bradycardia and paroxysmal atrial fibrillation (AF).
      BACKGROUND: Newer pacemakers have enhanced diagnostic features that permit
      detection and storage of detailed information about the frequency, duration, and
      time of onset of multiple episodes of AF, atrial tachycardia (AT), and
      ventricular tachycardia (VT). However, the prevalence and prognostic value of AF
      associated with rapid ventricular rates in the pacemaker population are unknown.
      METHODS: We prospectively followed 125 patients who received a Medtronic AT
      500/501 pacemaker for symptomatic bradycardia and paroxysmal AF. RESULTS: AF
      recurred in 112 patients (90%) during 22 +/- 8 months of follow-up. A total of
      1,324 VHR episodes occurred in 38 patients (30%). Episodes with available
      electrograms (n = 560) were reviewed and classified as AF (n = 279; 50%), AT (n =
      266; 47%) or VT (n = 15; 3%). AF burden was higher in patients with VHR episodes
      (median 1.9 vs 0.2 hours/day; P < .001). After controlling for AT/AF burden and
      heart disease, VHR episodes were a significant independent predictor of
      hospitalization for cardiovascular symptoms (odds ratio 2.92, 95% confidence
      interval 1.33-6.38; P = .007). Heart rate control improved over time in the
      cohort, and the frequency of VHR episodes decreased during follow-up (P < .001).
      CONCLUSIONS: VHR episodes documented in the pacemaker diagnostics identify a high
      risk subgroup of patients with AF. Monitoring VHR episodes may be useful for
      identifying pacemaker patients with AF who require more vigilant monitoring,
      additional investigations, and/or additional interventions.

PMID- 15851194
TI  - Catheter ablation guided by termination of postinfarction ventricular tachycardia
      by pacing with nonglobal capture.
AB  - OBJECTIVES: We prospectively investigated the prevalence and value of this
      criterion for identifying a target site for ablation in patients with
      postinfarction ventricular tachycardia (VT). BACKGROUND: Termination of
      postinfarction VT by pacing with nonglobal capture identifies a critical
      component of the reentrant circuit. METHODS: In a consecutive series of 34
      patients with prior infarction (age 67 +/- 10 years, ejection fraction 0.26 +/-
      0.1) referred for radiofrequency catheter ablation, mapping was performed in the
      left ventricle. At sites with abnormal electrograms, pacing was performed during
      VT. If VT terminated with nonglobal capture during the pacing train,
      radiofrequency energy was delivered. RESULTS: Sixty-two VTs (cycle length 450 +/-
      84 ms) were mapped and targeted for radiofrequency ablation. Concealed
      entrainment was present at 101 endocardial sites. Among the 101 sites, VT
      terminated by pacing with nonglobal capture at 5 sites (5%). At 10 additional
      sites in 10 patients, VT terminated by pacing with nonglobal capture, and
      concealed entrainment could not be documented at these sites because of
      reproducible termination of the VT. An application of radiofrequency energy
      resulted in VT termination at all 15 sites where nonglobal capture was documented
      and the targeted VTs were no longer inducible after ablation. CONCLUSIONS:
      Termination of VT by pacing with nonglobal capture can be demonstrated in
      approximately one third of patients with postinfarction VT and is a specific
      criterion for identifying a critical component of the reentrant circuit, whether
      or not concealed entrainment can be documented at that site.

PMID- 15851195
TI  - Simple and accurate catheter mapping technique to predict atrial fibrillation
      foci in the pulmonary veins or posterior right atrium.
AB  - OBJECTIVES: The purpose of this study was to investigate the efficacy of a novel
      catheter mapping technique for predicting atrial fibrillation (AF) foci.
      BACKGROUND: Most AF originates from pulmonary veins (PVs), but some originate
      from the right atrium. METHODS: We developed an algorithm by correlating the
      cardiac recordings obtained from multielectrode catheters placed in the posterior
      right atrium (RA) and esophagus during pacing from the PVs and superior vena cava
      (SVC) or crista terminalis (CT) in 10 AF patients. We tested the algorithm's
      accuracy prospectively in 46 AF patients. RESULTS: During pacing from the left
      PVs, the esophageal potentials preceded all other potentials. During pacing from
      both the right PVs and SVC-CT, the first component (FP) of the double potential
      (DP) recorded in the posterior RA preceded all other potentials. The amplitude of
      the FP was higher than that of the second DP component during pacing from the SVC
      CT, whereas the reverse occurred from the right PVs. The activation sequence of
      the FPs and esophageal potentials was from superior to inferior during pacing
      from the superior PVs, whereas the reverse occurred from the inferior PVs. The
      accuracy of predicting 34 foci in the right PVs, 28 foci in left PVs, and 6 foci
      in SVC-CT was 100% for all, respectively. The accuracy of discriminating foci in
      the superior PVs from those in the inferior PVs was 97% in the right PVs and 96%
      in the left PVs. CONCLUSIONS: The technique using mapping catheters placed in the
      posterior RA and esophagus is feasible and effective for mapping and ablating AF.

PMID- 15851196
TI  - Seasonal variation of mortality in the Antiarrhythmics Versus Implantable
      Defibrillators (AVID) study registry.
AB  - OBJECTIVES: We postulated that the pattern of death would be nonrandom with
      respect to temporal variables. BACKGROUND: Previous studies have demonstrated
      increased sudden death is associated with periods of relative stress, and overall
      mortality is associated with temporal variables. METHODS: In the Antiarrhythmics
      Versus Implantable Defibrillators (AVID) registry, vital status was obtained for
      4,450 patients (who had a recent episode of sustained ventricular arrhythmias or
      unexplained syncope and inducible ventricular tachycardia) through the National
      Death Index Service as of December 31, 1997 (follow-up 25.5 +/- 13.7 months).
      RESULTS: Mortality was not associated with the day of the week or with holidays
      but was associated with season (P = .033). Seasonal variation was present both in
      northern and southern sites. Mortality was higher during the winter months
      compared to the remaining months (111.2% in winter vs 96.5% in other months, P =
      .036). In addition, increased mortality was associated with a high-risk season
      variable defined (prior to evaluation of treatment arm associations) as spring in
      the north and winter in the south (P < .001). The hazard ratio for death
      associated with this "high-risk season" measured 1.25 (P = .001) compared to the
      other seasons in each region. A test of interaction between "high-risk" season
      and implantable cardioverter-defibrillator (ICD) status suggested that the group
      with ICDs experienced reduced mortality during the "high-risk season" compared to
      the group without ICDs (P = .047). CONCLUSIONS: Mortality was higher in the
      winter months and in the respective regional "high-risk" seasons. Furthermore,
      seasonal variation in mortality may have been due to variation in sudden
      arrhythmic death, and associated increases in mortality were reduced by ICD
      therapy.

PMID- 15851197
TI  - Intracellular calcium cycling, early afterdepolarizations, and reentry in
      simulated long QT syndrome.
AB  - OBJECTIVES: The purpose of this study was to investigate interactions between
      early afterdepolarizations (EADs) and reentry in long QT (LQT) syndromes.
      BACKGROUND: EADs, a characteristic feature of congenital and acquired LQT
      syndromes, are classically bradycardia dependent. Mechanisms by which they
      promote tachyarrhythmias such as torsades de pointes and ventricular fibrillation
      are not fully understood. Recent evidence suggests that EADs also may occur at
      rapid heart rates as a sequela of spontaneous sarcoplasmic reticulum (SR) Ca(2+)
      release related to intracellular Ca(2+) overload. Here, we performed computer
      simulations to explore the arrhythmogenic consequences of this phenomenon.
      METHODS: We used a modified version of the Luo-Rudy dynamic model in one
      dimensional and two-dimensional cardiac tissue with the time-dependent K(+)
      currents I(Kr) or I(Ks) reduced by 50% to simulate acquired and congenital LQT
      syndromes. RESULTS: (1) Spontaneous SR Ca(2+) release prolonged action potential
      duration but did not induce overt EADs unless K(+) current density was reduced to
      simulate acquired and congenital LQT syndromes. (2) In simulated LQT syndromes,
      EADs were capable of both terminating and reinitiating one-dimensional reentry.
      (3) A similar phenomenon in simulated 2D tissue led to reinitiation of spiral
      wave reentry that otherwise would have self-terminated. (4) Reentry reinitiation
      occurred only when the L-type Ca(2+) current and SR Ca(i) cycling were
      potentiated to simulate moderate sympathetic stimulation, consistent with the
      known arrhythmogenic effects of sympathetic activation (and protection by beta
      blockers) in LQT syndromes. CONCLUSIONS: These computer simulations suggest that
      EADs related to spontaneous SR Ca(2+) release can enhance arrhythmogenesis in LQT
      syndromes by reinitiating reentry.

PMID- 15851198
TI  - Early afterdepolarization-induced triggered activity: Initiation and reinitiation
      of reentrant arrhythmias.

PMID- 15851199
TI  - Optical mapping of the functional reentrant circuit of ventricular tachycardia in
      acute myocardial infarction.
AB  - OBJECTIVES: We used optical mapping to characterize the reentrant circuit of
      ventricular tachycardia (VT) during acute myocardial infarction (MI) in isolated
      canine left ventricular preparations. BACKGROUND: The nature of the reentrant
      circuit that underlies VT during acute MI is not well understood. METHODS: Using
      optical mapping in isolated canine left ventricular preparations, we
      characterized the reentrant circuit of monomorphic VT (mean cycle length 245.3 +/
      15.6 ms, n = 7) induced by programmed stimulation during acute MI. RESULTS:
      Optical mapping during VT revealed a functional reentrant circuit consisting of
      four components: (1) a protected isthmus located between the infarction area and
      the functional line of block; (2) an entrance site located at one end of the
      isthmus; (3) an exit site located at the other end of the isthmus; and (4) an
      outer loop consisting of nonischemic normal tissue, connecting the exit and
      entrance sites. Rate-dependent slow conduction within the border zone was
      associated with significant changes (n = 6) in action potential amplitude (99.1
      +/- 0.4 vs 71.4 +/- 0.6 mV, P < .01), maximal diastolic potential (-80.6 +/- 0.2
      vs -65.4 +/- 0.6 mV, P < .05), action potential duration at 90% repolarization
      (APD(90); 188.4 +/- 1.0 vs 164.3 +/- 3.1 ms, P < .05), and dV/dt (302.4 +/- 7.9
      vs 168.5 +/- 3.6 V/s, P < .05). Compared to preparations with no inducible VT (n
      = 7), formation of a functional line of block was the key mechanism for
      initiation of functional reentry in preparations with VT. When comparing
      preparations with sustained and nonsustained VT, preservation of slow conduction
      over the isthmus was the key component for maintenance of sustained VT.
      CONCLUSIONS: The reentrant circuit of monomorphic VT in the setting of acute MI
      involved both the infarction border zone and nonischemic normal tissue. The
      underlying mechanism is related to the presence of rate-dependent slow conduction
      and the development of a functional line of block in the border zone.

PMID- 15851200
TI  - Ionic current abnormalities associated with prolonged action potentials in
      cardiomyocytes from diseased human right ventricles.
AB  - OBJECTIVES: This study was designed to determine whether ionic currents in right
      ventricular myocytes from explanted human transplant recipient hearts are related
      to right ventricular histopathology and function. BACKGROUND: Cardiac action
      potential duration (APD) is prolonged in ventricular tissues/cells from patients
      with heart failure, but the ionic mechanisms are not well documented. METHODS:
      Membrane currents and transmembrane action potentials in myocytes from right
      ventricular epicardium of explanted human hearts were recorded using whole-cell
      patch clamp technique. Data from cells from right ventricles with severe
      histologic and functional abnormalities (abnormal histology group [AH]) and from
      right ventricles with preserved histology and function (relatively normal
      histology group [RNH]) were compared. RESULTS: We found that APD at 50% (APD(50))
      and 90% repolarization (APD(90)) were significantly longer in AH cells than in
      RNH cells. Early afterdepolarizations (EADs) were observed in 20% of AH cells and
      none of the RNH cells. Inwardly rectifying K(+) current (I(K1)) was decreased
      (both inward and outward components). Both transient outward K(+) current
      (I(to1)) and slowly delayed rectifier K(+) current (I(Ks)) were down-regulated in
      AH cells. L-type Ca(2+) (I(Ca.L)) was not altered in AH cells. CONCLUSIONS:
      I(K1), I(to1), and I(Ks) are down-regulated in AH cells of human heart failure.
      This down-regulation contributes to APD prolongation that favors the occurrence
      of arrhythmogenic EADs and suggests a link between human cardiac
      histopathologic/functional abnormalities and arrhythmogenic ionic remodeling.

PMID- 15851201
TI  - Achieving regular slow rhythm during atrial fibrillation without atrioventricular
      nodal ablation: selective vagal stimulation plus ventricular pacing.
AB  - OBJECTIVES: The aim of this study was to achieve regular slow ventricular rhythm
      during atrial fibrillation (AF) without destroying the AV node (AVN). BACKGROUND:
      Recent experimental and clinical studies have demonstrated that selective AVN
      vagal stimulation (AVN-VS) can be used to slow ventricular rate during AF;
      however, an irregular rhythm remains. Alternatively, ventricular on-demand (VVI)
      pacing achieves rate regularization but at rates faster than the already fast
      intrinsic rate during AF. We hypothesized that AVN-VS combined with VVI pacing
      would achieve slow, regular rhythm during AF without requiring AVN ablation.
      METHODS: AF was induced in eight dogs. AVN-VS was applied to the epicardial fat
      pad that projects vagal nerve fibers to the AVN. A computer-controlled algorithm
      adjusted AVN-VS intensity to achieve three levels of mean ventricular RR
      interval: 75%, 100%, or 125% of the spontaneous sinus cycle length. At each of
      the three levels, concomitant VVI pacing was delivered at a constant cycle length
      equal to the corresponding target. Hemodynamic measurements were performed during
      the study to elucidate the advantages of the proposed method. RESULTS: AF
      resulted in rapid, irregular ventricular rates (RR = 287 +/- 36 ms, or 56% of
      sinus cycle length). AVN-VS achieved average ventricular rate slowing to the
      three target levels in all dogs (RR increased to 381 +/- 41, 508 +/- 54, and 632
      +/- 68 ms, respectively). At each of the three target rate levels, AVN-VS
      combined with VVI pacing fully eliminated rate irregularities. The regular slow
      ventricular rhythms during AF were associated with significant hemodynamic
      improvement. CONCLUSIONS: A novel approach combining AVN-VS with VVI pacing
      results in a regular, slow ventricular rhythm during AF that does not necessitate
      AVN ablation. Rate regularization achieved by this approach was associated with
      pronounced hemodynamic benefits during AF.

PMID- 15851202
TI  - Effect of plunge electrodes in active cardiac tissue with curving fibers.
AB  - OBJECTIVES: Our goal is to determine if plunge electrodes change how the heart
      responds to electrical stimulation. BACKGROUND: Several experiments designed to
      study the induction of a rotor in cardiac tissue have used plunge electrodes to
      measure the transmural potential. It is our hypothesis that these electrodes may
      have affected the electrical response of the tissue to a shock. METHODS: We
      previously have shown that a single plunge electrode in two-dimensional, passive
      cardiac tissue induces a significant transmembrane potential when stimulated by a
      large shock. In this study, we expand our simulation to include an array of nine
      electrodes in active tissue with curving fibers. We compare the thresholds for
      rotor induction in tissue with and without electrodes by initiating a planar S1
      wavefront and then stimulating the tissue at different intervals with a uniform
      S2 electric field perpendicular to S1. In tissue without plunge electrodes,
      virtual electrode polarization due to the curving fibers is generally widespread
      over the entire tissue, whereas polarization tends to be localized around the
      electrodes in tissue including them. RESULTS: Our results show that at some S1-S2
      intervals, the presence of plunge electrodes can result in reentry when it
      otherwise would not be possible. For other S1-S2 intervals, such as during the
      vulnerable period when the reentry threshold is at a minimum, the induction of
      reentry is unaffected by the presence of plunge electrodes. CONCLUSIONS: Plunge
      electrodes can play an important role during the stimulation of cardiac tissue,
      but this is highly dependent on the chosen S1-S2 interval.

PMID- 15851203
TI  - Frank-Starling mechanism contributes modestly to ventricular performance during
      atrial fibrillation.
AB  - OBJECTIVES: The aim of this study was to assess whether Frank-Starling mechanism
      has an independent effect on left ventricular (LV) performance in atrial
      fibrillation (AF). BACKGROUND: Ventricular performance in AF depends on variable
      contractility through the interval-force mechanism based on the ratio of
      preceding and pre-preceding RR intervals (RR(p)/RR(pp)). The impact of end
      diastolic volume (EDV) variability, through the Frank-Starling mechanism, is not
      well understood. METHODS: We induced AF in 16 open chest dogs. RR intervals, LV
      pressure, LV volume, and aortic flow were collected for >400 beats during rapid
      AF (ventricular cycle length 292 +/- 66 ms). In six of the dogs, additional data
      were collected while average ventricular cycle length was prolonged from 258 +/-
      34 ms to 445 +/- 80 ms by selective vagal nerve stimulation of the AV node.
      RESULTS: The relations of maximal LV power (LVPower) and peak LV pressure
      derivative (dP/dt) versus RR(p)/RR(pp) were fitted to the equation y = A * (1 -
      EXP (RR(p)/RR(pp)min - RR(p)/RR(pp))/C) and the residuals (RES) of these
      relations were analyzed. LVPower and dP/dt strongly correlated with RR(p)/RR(pp)
      (r(2) = 0.67 +/- 0.12 and 0.66 +/- 0.12, P < .0001 for all correlations).
      Importantly, RES-LVPower and RES-dP/dt showed linear correlation with EDV (r(2) =
      0.20 +/- 0.14 and r(2) = 0.24 +/- 0.17, P < .01 for all correlations). In the six
      dogs with slowed average ventricular rate, the slope of both residual
      relationships (RES-LVPower vs EDV and RES- dP/dt vs EDV) decreased (P < .03 for
      both). CONCLUSIONS: The Frank-Starling mechanism contributes to ventricular
      performance in AF independently of the interval-force effects of the beat-to-beat
      variability in cardiac contractility. The Frank-Starling mechanism is sensitive
      to the average ventricular rate.

PMID- 15851204
TI  - Catheter ablation of ventricular tachycardia guided by contrast-enhanced cardiac
      computed tomography.
AB  - We describe catheter ablation of recurrent ventricular tachycardia using high
      resolution definition of a myocardial infarct scar by contrast-enhanced cardiac
      computed tomography (CT). Positron emission tomography scanning as well as three
      dimensional electroanatomic mapping confirmed the extent of scar prior to
      ablation. Catheter ablation based on substrate mapping was successful in
      eliminating the ventricular tachycardia. Detection of scar by cardiac CT has the
      potential to abbreviate voltage/substrate mapping in the electrophysiology
      laboratory. To our knowledge, this is the first time myocardial scar was defined
      by cardiac CT and utilized for defining an ablation strategy for ventricular
      tachycardia.

PMID- 15851205
TI  - Unique self-perpetuating cycle of atrioventricular block and phase IV bundle
      branch block in a patient with bundle branch reentrant tachycardia.
AB  - Bundle branch reentrant tachycardia (BBRT) is an uncommon form of ventricular
      tachycardia involving diseased bundle branches. Phase IV bundle branch block also
      accompanies severe His-Purkinje disease. We present an unusual case of BBRT in a
      patient who also manifests a unique self-perpetuating cycle of AV block and phase
      IV left bundle branch block following aortic valve surgery. BBRT was treated
      successfully by ablation of the right bundle.

PMID- 15851206
TI  - Preexcitation masking underlying aberrant conduction: an atriofascicular
      accessory pathway functioning as an ectopic right bundle branch.
AB  - Preexcitation and aberrant conduction both cause a broad QRS complex. An unusual
      case of an atriofascicular accessory pathway effectively functioning as an
      ectopic right bundle branch and responsible for both physiologically normal
      ventricular activation and pathologic preexcited tachycardias as part of a split
      AV node-bundle branch system is presented.

PMID- 15851207
TI  - Cell size and communication: role in structural and electrical development and
      remodeling of the heart.
AB  - With the advent of new information about alterations of cardiac gap junctions in
      disease conditions associated with arrhythmias, there have been major advances in
      the genetic and metabolic manipulation of gap junctions. In contrast, in
      naturally occurring cardiac preparations, little is known about cell-to-cell
      transmission and the subcellular events of propagation or about structural
      mechanisms that may affect conduction events at this small size scale. Therefore,
      the aim of this article is to review results that produce the following unifying
      picture: changes in cardiac conduction due to remodeling cardiac morphology
      ultimately are limited to changes in three morphologic parameters: (1) cell
      geometry (size and shape), (2) gap junctions (distribution and conductivity), and
      (3) interstitial space (size and distribution). In this article, we consider
      changes in conduction that result from the remodeling of cell size and gap
      junction distribution that occurs with developmental ventricular hypertrophy from
      birth to maturity. We then go on to changes in longitudinal and transverse
      propagation in aging human atrial bundles that are produced by remodeling
      interstitial space due to deposition of collagenous septa. At present,
      experimental limitations in naturally occurring preparations prevent measurement
      of the conductance of individual gap junctional plaques, as well as the delays in
      conduction associated with cell-to-cell transmission. Therefore, we consider the
      development of mathematical electrical models based on documented cardiac
      microstructure to gain insight into the role of specific morphologic parameters
      in generating the changes in anisotropic propagation that we measured in the
      tissue preparations. A major antiarrhythmic implication of the results is that an
      "indirect" therapeutic target is interstitial collagen, because regulation of its
      deposition and turnover to prevent or alter microfibrosis can enhance side-to
      side electrical coupling between small groups of cells in aging atrial bundles.

PMID- 15851208
TI  - Non-antiarrhythmic drugs to prevent atrial fibrillation.

PMID- 15851209
TI  - Paroxysmal supraventricular tachycardia in a patient with a markedly prolonged PR
      interval.

PMID- 15851210
TI  - Enhanced left atrial mapping using digitally synchronized NavX three-dimensional
      nonfluoroscopic mapping and high-resolution computed tomographic imaging for
      catheter ablation of atrial fibrillation.

PMID- 15851211
TI  - Understanding electromagnetic interference.

PMID- 15851212
TI  - Obituary to Philippe Coumel, MD, 1935-2004.

PMID- 15851213
TI  - Biomedical research and the public domain.

PMID- 15851215
TI  - Language and interpretation of clinical trial outcomes: alternates, surrogates,
      and composites.

PMID- 15851214
TI  - Alternative endpoints for mortality in studies of patients with atrial
      fibrillation: the AFFIRM study experience.
AB  - OBJECTIVES: The purpose of this study was to examine possible alternatives for
      death, particularly hospitalization for cardiovascular reasons (CV
      hospitalization), as an endpoint in studies of atrial fibrillation (AF) using the
      Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM)
      database. BACKGROUND: AF is associated with increased mortality, but large
      numbers of patients are needed to demonstrate even a moderate effect of a therapy
      on mortality. METHODS: AFFIRM studied 4,060 patients with AF, randomized to
      either rate-control or rhythm-control strategy with death as the primary
      endpoint. RESULTS: Only CV hospitalization occurred more frequently than death.
      Like death, CV hospitalization was more frequent in the rhythm-control arm (46%
      vs 36%, P < .001) overall but not in a cohort that attempted to exclude those CV
      hospitalizations possibly related to treatment strategy (e.g., cardioversion, 24%
      vs 27%). In either model there was no interaction of CV hospitalization (analyzed
      as a time-dependent covariate) with treatment arm (P = .18 and P = .21,
      respectively). CV hospitalization was highly predictive of death in both
      treatment arms (P < .001) in either model, but after this event, there was no
      difference in time to death. A composite endpoint of CV hospitalization combined
      with death might increase power and reduce the size of trials of therapy for AF
      in such patients. CONCLUSIONS: In patients with AF such as those in the AFFIRM
      study, CV hospitalization has many attributes of a surrogate for mortality. More
      research on CV hospitalization, alone or as part of a composite endpoint, is
      warranted.

PMID- 15851216
TI  - Randomized controlled study of detection enhancements versus rate-only detection
      to prevent inappropriate therapy in a dual-chamber implantable cardioverter
      defibrillator.
AB  - OBJECTIVES: The purpose of this study was to compare rate-only detection to
      enhanced detection in a dual-chamber implantable cardioverter-defibrillator
      (ICD), to discriminate ventricular tachycardia from supraventricular tachycardia.
      BACKGROUND: ICDs are highly effective in treating ventricular tachycardia (VT) or
      ventricular fibrillation (VF). However, they frequently deliver inappropriate
      therapy during supraventricular tachycardia (SVT). METHODS: We conducted a
      randomized clinical trial of detection enhancements in a dual-chamber ICD
      compared to control (rate-only) detection to discriminate VT from SVT. Detection
      enhancements included a specific standardized protocol identical for all patients
      for programming rate stability, sudden onset, atrial-to-ventricular relationship
      (sudden onset = 9% and rate stability = 10 ms; V > A "on"), and "sustained rate
      duration" (3 minutes). The primary endpoint was the time to first inappropriate
      therapy classified by a blinded events committee. RESULTS: One hundred forty-nine
      patients had a history of sustained VT or VF. Mean age (+/- SD) was 60 +/- 13
      years; 83% were male, and mean ejection fraction was 35 +/- 15%. Control (n = 70)
      and "enhanced" (n = 79) groups did not differ with regard to age, sex, ejection
      fraction, or primary arrhythmia. The proportion of patients free of inappropriate
      therapy over time was significantly higher in the enhanced versus the control
      group (hazard ratio = 0.47, P = .011). High-energy shocks were reduced from 0.58
      +/- 4.23 shocks/patient/month in the control group to 0.04 +/- 0.15
      shocks/patient/month in the enhanced group (P = .0425). No patient programmed per
      protocol failed to receive therapy for VT detected by the ICD (422 VT episodes).
      CONCLUSIONS: Standardized programming in a dual-chamber ICD leads to a
      significant and clinically important reduction in inappropriate therapies
      compared to rate-only detection and does not compromise safety with respect to
      appropriate treatment of VT.

PMID- 15851217
TI  - Deterioration of interatrial conduction in patients with paroxysmal atrial
      fibrillation: electroanatomic mapping of the right atrium and coronary sinus.
AB  - OBJECTIVES: The purpose of this study was to analyze the velocities across the
      coronary sinus ostium (cross-CSo) and within the coronary sinus (intra-CS) in
      patients with and without paroxysmal atrial (AF) fibrillation and to estimate the
      interatrial conduction deterioration area in AF patients. BACKGROUND: Interatrial
      conduction delay in AF patients has been reported. However, localization of the
      interatrial conduction delay still is not clear. METHODS: Thirteen patients with
      paroxysmal AF and 10 control patients with AV nodal reentrant tachycardia or
      ectopic atrial tachycardia were enrolled in the study. Right atrial and CS
      mapping were performed using the CARTO electroanatomic mapping system during
      sinus rhythm and during distal CS pacing. The activation times and spatial
      distances of cross-CSo and intra-CS were measured between paired sites, from
      which the activation velocities of cross-CSo and intra-CS were obtained. RESULTS:
      During sinus rhythm, the activation velocities of cross-CSo in the AF group (1.2
      +/- 0.2 m/s) were significantly slower than those in the control group (2.9 +/-
      1.6 m/s, P < .05). During distal CS pacing, the cross-CSo velocities of the AF
      group (1.0 +/- 0.5 m/s) also appeared slower than those in the control group (1.4
      +/- 0.2 m/s, P = .07). However, no difference was found in intra-CS activation
      velocities between the two groups (2.8 +/- 1.9 vs 3.2 +/- 2.2 m/s and 1.5 +/- 0.3
      vs 1.4 +/- 0.3 m/s, P > .05 during sinus rhythm and distal CS pacing,
      respectively). CONCLUSIONS: Interatrial conduction at the posteroparaseptal
      region across the CS ostium was significantly slower in patients with paroxysmal
      AF than in control patients, further supporting the link between interatrial
      conduction deterioration and paroxysmal AF.

PMID- 15851218
TI  - Transient atrioventricular conduction block with cryoablation following normal
      cryomapping.
AB  - OBJECTIVES: The purpose of this study was to demonstrate that adverse but
      reversible effects on AV conduction may be observed during cryoablation despite
      no evidence of deleterious effects evident during cryomapping. BACKGROUND:
      Transcatheter cryoablation has recently been introduced for treatment of
      supraventricular tachycardia. Potential advantages compared with radiofrequency
      ablation include decreased risk of thromboembolism and perforation, less patient
      discomfort, more sharply demarcated lesions, and decreased risk of inadvertent
      damage to adjacent structures due to the ability to observe the
      electrophysiologic effects of lesion generation prior to permanent tissue damage.
      Occasionally, however, adverse electrophysiologic effects may be observed during
      cryoablation when prior cryomapping suggests a safe location. METHODS: We
      reviewed the experience with our first 32 consecutive patients who underwent
      cryoablation for supraventricular tachycardia. Patients who experienced transient
      heart block during cryoablation following uneventful cryomapping were identified.
      RESULTS: Five patients in whom cryomapping was performed with no evidence for
      deleterious effects on AV conduction were identified. However, application of
      cryoablation at these mapped sites resulted in transient complete heart block.
      This experience demonstrates that the cryolesion created during cryoablation may
      expand relative to that suggested by cryomapping. CONCLUSIONS: It is important to
      maintain vigilance in monitoring for AV nodal conduction abnormalities during
      cryoablation, even when cryomapping suggests a safe location for cryoablation.

PMID- 15851219
TI  - Successful release of entrapped circumferential mapping catheters in patients
      undergoing pulmonary vein isolation for atrial fibrillation.
AB  - OBJECTIVES: The purpose of this study was to demonstrate a method for successful
      and safe release of an entrapped circular catheter. BACKGROUND: Segmental
      pulmonary vein (PV) isolation is widely practiced for patients with symptomatic
      drug-refractory atrial fibrillation. A circular mapping catheter is sometimes
      used with this technique to map the electrical connection between the left atrium
      (LA) and the PVs. This catheter reportedly can become entrapped in the mitral
      valve apparatus. Attempts to free the entrapped catheter can result in serious
      complications, including damage to the mitral valve chordae tendineae or fracture
      of the catheter itself. METHODS: Three patients were referred for PV isolation
      for atrial fibrillation. A circular mapping catheter was used to map the sites of
      LA-PV electrical connections. RESULTS: During the procedure, the circular mapping
      catheter became entrapped in the mitral valve apparatus in two patients and in
      the PV in one patient. A series of maneuvers, which included use of another
      catheter and guiding sheaths as well as pushing forward rather than pulling back
      on the entrapped catheter, allowed safe and successful release of the entrapped
      catheter in all patients. CONCLUSIONS: Entrapment of the circular mapping in the
      mitral valve apparatus or the PVs during PV isolation is a rare complication
      associated with use this catheter. We describe a series of maneuvers that may
      allow safe and successful release of the entrapped catheter.

PMID- 15851220
TI  - Randomized prospective trial of atrioventricular delay programming for cardiac
      resynchronization therapy.
AB  - OBJECTIVES: The purpose of this study was to determine if AV delay optimization
      with continuous-wave Doppler aortic velocity-time integral (VTI) is clinically
      superior to an empiric program in patients treated with cardiac resynchronization
      therapy (CRT) for severe heart failure. BACKGROUND: The impact of AV delay
      programming on clinical outcomes associated with CRT is unknown. METHODS: A
      randomized, prospective, single-blind clinical trial was performed to compare two
      methods of AV delay programming in 40 patients with severe heart failure referred
      for CRT. Patients were randomized to either an optimized AV delay determined by
      Doppler echocardiography (group 1, n = 20) or an empiric AV delay of 120 ms
      (group 2, n = 20) with both groups programmed in the atriosynchronous
      biventricular pacing (VDD) mode. Optimal AV delay was defined as the AV delay
      that yielded the largest aortic VTI at one of eight tested AV intervals (between
      60 and 200 ms). New York Heart Association (NYHA) functional classification and
      quality-of-life (QOL) score were compared 3 months after randomization. RESULTS:
      Immediately after CRT initiation with AV delay programming, VTI improved by 4.0
      +/- 1.7 cm vs 1.8 +/- 3.6 cm (P < .02), and ejection fraction (EF) increased by
      7.8 +/- 6.2% vs 3.4 +/- 4.4% (P < .02) in group 1 vs group 2, respectively. After
      3 months, NYHA classification improved by 1.0 +/- 0.5 vs 0.4 +/- 0.6 class points
      (P < .01), and QOL score improved by 23 +/- 13 versus 13 +/- 11 points (P < .03)
      for group 1 vs group 2, respectively. CONCLUSIONS: Echocardiography-guided AV
      delay optimization using the aortic Doppler VTI improves clinical outcomes at 3
      months compared to an empiric AV delay program of 120 ms.

PMID- 15851221
TI  - Cardiac resynchronization therapy optimization by finger plethysmography.
AB  - OBJECTIVES: We tested a simple noninvasive method for cardiac resynchronization
      therapy (CRT) optimization using standard finger photoplethysmography (FPPG).
      BACKGROUND: CRT can increase left ventricular cardiac output in patients with
      heart failure and ventricular conduction delay. Optimal therapy delivery depends
      on an appropriate AV delay. Multiple invasive and noninvasive methods have been
      attempted to identify patients and the best AV delay for CRT, but all suffer from
      a combination of high patient risk, cost, complexity, and low reproducibility.
      METHODS: FPPG and invasive aortic pressure data were simultaneously collected
      from 57 heart failure patients during intrinsic rhythm alternating with very
      brief periods of pacing at 4 to 5 AV delays. After correcting data for artifacts,
      the median percentage responses for each AV delay were classified as positive,
      negative, or neutral compared to baseline (Wilcoxon rank test). RESULTS: FPPG
      correctly identified positive aortic pulse pressure responses with 71%
      sensitivity (95% CI: 60-80%) and 90% specificity (95% CI: 84-94%) and negative
      aortic pulse pressure responses with 57% sensitivity (95% CI: 44-69%) and 96%
      specificity (95% CI: 91-98%). The magnitude of FPPG changes were strongly
      correlated with positive aortic pulse pressure changes (R(2) = 0.73, P < .0001)
      but less well correlated with negative aortic pulse pressure changes (R(2) =
      0.43, P < .0001). FPPG selected 78% of the patients having positive aortic pulse
      pressure changes to CRT and identified the AV delay giving maximum aortic pulse
      pressure change in all selected patients. CONCLUSIONS: FPPG can provide a simple
      noninvasive method for identifying significant changes in aortic pulse pressure
      with high specificity, including identifying patients in whom aortic pulse
      pressure increases with CRT and the AV delay giving the maximum aortic pulse
      pressure.

PMID- 15851222
TI  - Effects of left atrial ablation of atrial fibrillation on size of the left atrium
      and pulmonary veins.
AB  - OBJECTIVES: The purpose of this study was to determine the effect of left atrial
      circumferential ablation on the size of the left atrium and pulmonary veins
      (PVs). BACKGROUND: The long-term effects of left atrial circumferential ablation
      on left atrial and PV size and anatomy have not been analyzed in quantitative
      fashion. METHODS: PV and left atrial sizes were analyzed in 41 consecutive
      patients (mean age 54 +/- 12 years) with paroxysmal (n = 25) or chronic (n = 16)
      atrial fibrillation. Computed tomography of the chest with three-dimensional
      reconstruction was performed before and 4 +/- 2 months after left atrial
      circumferential ablation. Left atrial circumferential ablation was performed to
      encircle the PVs 1 to 2 cm from the ostia, using a power output of 70 W.
      Additional ablation lines were created in the posterior left atrium and mitral
      isthmus. Radiofrequency energy also was delivered within the circles and at the
      PV ostia in 51% of patients at a reduced power output of 35 W. RESULTS: At 6
      months, 36 patients (88%) were in sinus rhythm without antiarrhythmic drug
      therapy, including 3 patients (7%) who developed persistent left atrial flutter
      and underwent subsequent successful ablation of atrial flutter. There was a 15 +/
      16% decrease in left atrial volume (P < .01) and 10 +/- 35% decrease in PV
      ostial area (P < .01), without focal narrowing, in patients with a successful
      outcome. Focal PV stenosis did not occur in any of the 41 patients. CONCLUSIONS:
      Maintenance of sinus rhythm after left atrial circumferential ablation is
      associated with reduced left atrial and PV ostial size. Left atrial
      circumferential ablation for atrial fibrillation does not cause PV stenosis.

PMID- 15851223
TI  - Right and left inferior extensions of the atrioventricular node may represent the
      anatomic substrate of the slow pathway in humans.
AB  - OBJECTIVES: The purpose of this study was to investigate the electrophysiologic
      characteristics of the inferior extensions of the human atrioventricular (AV)
      node and their possible relationship to slow pathway conduction. BACKGROUND: The
      human heart contains right and left inferior extensions of the AV node that
      relate to right and left atrial inputs. METHODS: Fourteen patients admitted for
      catheter ablation of left-sided accessory pathways were studied. Atrial pacing
      was performed from multiple sites in both atria, and simultaneous His-bundle
      recordings from right and left sides of the septum were made. RESULTS:
      Significant differences of A-H and stimulus to His (St-H) intervals with pacing
      at various sites were found. St-H intervals were similar during constant pacing
      from the low right atrium or the left inferoparaseptal area (112 +/- 28 ms vs 112
      +/- 26 ms, P = .8, for right His recordings and 114 +/- 23 ms vs 111 +/- 25 ms, P
      = .9, for left His recordings). At maximum decrement, there were significantly
      shorter St-H intervals during left inferoparaseptal pacing compared to low right
      atrial pacing (201 +/- 24 ms vs 218 +/- 44 ms, P = .02, for right His recordings,
      and 200 +/- 24 ms vs 219 +/- 41 ms, P = .009, for left His recordings).
      Differences on right His recordings between St-H intervals at maximum decrement
      and at constant pacing from the low right atrium were significantly higher than
      corresponding differences on left His recordings during pacing from the left
      inferoparaseptal area (P = .035). CONCLUSIONS: Our findings support the concept
      that the right and left inferior extensions of the human AV node may represent
      the anatomic substrate of the slow pathway as defined electrophysiologically.

PMID- 15851224
TI  - Is idiopathic ventricular fibrillation a short QT syndrome? Comparison of QT
      intervals of patients with idiopathic ventricular fibrillation and healthy
      controls.
AB  - OBJECTIVE: The purpose of this study was to determine if patients with idiopathic
      ventricular fibrillation (VF) have shorter QT intervals than comparable healthy
      controls. BACKGROUND: The upper limit of the normal QT is well defined. Less is
      known about the lower limit of the normal QT. Patients with the recently
      described "short QT syndrome" have characteristics resembling those of patients
      with idiopathic VF. METHODS: The ECGs of 28 consecutive patients with idiopathic
      VF (17 men and 11 women, age 31 +/- 17 years) were compared to those of 270 age-
      and gender- matched healthy controls. Based on published literature, we defined
      "short QT" as QTc < or = 360 ms for males and < or = 370 ms for females. RESULTS:
      Despite significant overlapping, the QTc of males with idiopathic VF was shorter
      than the QTc of healthy males (371 +/- 22 ms vs 385 +/- 19 ms, P = .034). Short
      QT intervals were found more frequently among males with idiopathic VF (35% vs
      10%, P = .003). No such differences were apparent among women. Short QTc
      intervals were more commonly seen during bradycardia. However, the correlation
      between short QT and a history of VF was independent of heart rate. CONCLUSIONS:
      "Short" QTc values are commonly seen in male patients with idiopathic VF.
      However, "short" QTc values are not rare among healthy adults, especially at slow
      heart rates. Further studies are needed to define when a given QT is really "too
      short."

PMID- 15851225
TI  - Idiopathic VF and short repolarization: intriguing new concept.

PMID- 15851226
TI  - Single cryothermia applications of less than five minutes produce permanent
      cavotricuspid isthmus block in humans.
AB  - OBJECTIVES: The aim of this study was to compare single-3-minute (single-3) with
      double-3-minute (double-3) cryothermia applications for treatment of atrial
      flutter (AFL). BACKGROUND: Previous animal studies have indicated the need for a
      double 5-minute cryothermal application to create large and permanent lesions.
      METHODS: Forty patients (56 +/- 13 years old) with typical AFL (cycle length 229
      +/- 35 ms) were randomized to single-3 (n = 20) or double-3 (n = 20) cryothermia
      applications at each site along the cavotricuspid isthmus (CTI). Cryoablation was
      performed with the CryoCor cryoablation system. A successful procedure was
      defined as noninducibility of AFL with the concomitant presence of bidirectional
      CTI conduction block under isoproterenol infusion. RESULTS: All but 1 patient
      (95%) of the single-3 group and all patients (100%) of the double-3 group were
      successfully ablated. The number of sites needed to create isthmus conduction
      block was 9 +/- 4 (single-3) and 8 +/- 2 (double-3) (NS). Fluoroscopy time did
      not differ between the two groups (single-3: 31 +/- 14; double-3: 36 +/- 17 min,
      NS). The procedure time of the single-3 group was significantly shorter compared
      to the procedure time of the double-3 group (mean procedure duration 132 +/- 64
      vs 159 +/- 50 min, P < .04). After a mean follow-up of 11.7 +/- 4.7 months, two
      recurrences of AFL occurred in the double-3 group. CONCLUSIONS: Single
      cryothermia applications of 3 minutes produce permanent CTI conduction block in
      patients with typical AFL and significantly reduce procedure duration.

PMID- 15851227
TI  - Spectrum and prevalence of cardiac sodium channel variants among black, white,
      Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility
      and Brugada/long QT syndrome genetic testing.
AB  - OBJECTIVES: The purpose of this study was to determine the prevalence and
      spectrum of nonsynonymous polymorphisms (amino acid variants) in the cardiac
      sodium channel among healthy subjects. BACKGROUND: Pathogenic mutations in the
      cardiac sodium channel gene, SCN5A, cause approximately 15 to 20% of Brugada
      syndrome (BrS1), 5 to 10% of long QT syndrome (LQT3), and 2 to 5% of sudden
      infant death syndrome. METHODS: Using single-stranded conformation polymorphism,
      denaturing high-performance liquid chromatography, and/or direct DNA sequencing,
      mutational analysis of the protein-encoding exons of SCN5A was performed on 829
      unrelated, anonymous healthy subjects: 319 black, 295 white, 112 Asian, and 103
      Hispanic. RESULTS: In addition to the four known common polymorphisms (R34C,
      H558R, S1103Y, and R1193Q), four relatively ethnic-specific polymorphisms were
      identified: R481W, S524Y, P1090L, and V1951L. Overall, 39 distinct missense
      variants (28 novel) were elucidated. Nineteen variants (49%) were found only in
      the black cohort. Only seven variants (18%) localized to transmembrane-spanning
      domains. Four variants (F1293S, R1512W, and V1951L cited previously as BrS1
      causing mutations and S1787N previously published as a possible LQT3-causing
      mutation) were identified in this healthy cohort. CONCLUSIONS: This study
      provides the first comprehensive determination of the prevalence and spectrum of
      cardiac sodium channel variants in healthy subjects from four distinct ethnic
      groups. This compendium of SCN5A variants is critical for proper interpretation
      of SCN5A genetic testing and provides an essential hit list of targets for future
      functional studies to determine whether or not any of these variants mediate
      genetic susceptibility for arrhythmias in the setting of either drugs or disease.

PMID- 15851228
TI  - Novel pore mutation in SCN5A manifests as a spectrum of phenotypes ranging from
      atrial flutter, conduction disease, and Brugada syndrome to sudden cardiac death.
AB  - OBJECTIVES: The purpose of this study was to determine the clinical and
      biophysical characteristics of a novel SCN5A mutation. BACKGROUND: Brugada
      syndrome and isolated cardiac conduction defect have been linked to SCN5A
      mutations. METHODS: Eleven members of a western European family underwent
      electrophysiologic investigations and mutation analysis of the SCN5A gene. Wild
      type and mutant SCN5A channels were expressed in HEK293 cells, and whole cell
      currents were studied using patch clamp procedures. RESULTS: A novel mutation,
      R376H, in the first pore segment of SCN5A variably causes Brugada syndrome and/or
      conduction disease in a single family. Biophysical analysis demonstrated a
      significant current reduction for the mutant, a pathophysiologic profile
      consistent with Brugada syndrome and isolated cardiac conduction defect. Among 11
      family members, 9 were carriers of the mutation. The proband's initial
      presentation was a saddleback Brugada ECG, atrial flutter, and diffuse conduction
      disturbances. He had no inducible ventricular arrhythmias but experienced sudden
      cardiac death. His brother was affected by atrial flutter and had a clear
      conduction disorder, but he did not display baseline or evocable ECG signs of
      Brugada syndrome. He received an implantable cardioverter-defibrillator that
      delivered one appropriate shock after 1 year of follow-up. The phenotype in the
      family members was highly variable and ranged from noninducible and inducible
      asymptomatic carriers of the mutations to isolated conduction disease and to
      symptomatic Brugada syndrome. CONCLUSIONS: We describe the functional
      characterization of a novel SCN5A pore mutation, R376H, with variable clinical
      expression in the same family. Differentiating between electrophysiologic
      entities (Brugada syndrome-isolated cardiac conduction defect) is more
      challenging. Recognition of factors modifying the clinical presentation may be
      important for clinical decision making.

PMID- 15851229
TI  - Activation sequences following failed atrial defibrillation.
AB  - OBJECTIVES: The purposes of this study were to examine the first activations
      following atrial defibrillation shocks to help understand how and where atrial
      fibrillation (AF) relapsed following failed shocks and to assess the difference
      in postshock activation between failed and successful shocks. BACKGROUND: While
      many studies have investigated the mechanism of ventricular defibrillation, much
      less is known about the mechanisms of AF. METHODS: Sustained AF was induced
      electrically after pericardial infusion of methylcholine in 10 sheep. Biphasic
      subthreshold shocks were delivered to three configurations: right atrium to
      distal coronary sinus (RA-CS), sequential shocks with RA-CS as the first pathway
      followed by proximal CS to superior vena cava as the second pathway (Sequential),
      and right ventricle to superior vena cava plus can (V-triad). In eight sheep,
      global atrial mapping was performed with 504 electrodes spaced 3 to 4 mm apart.
      RESULTS: Earliest postshock activations mostly arose from the left atrium for V
      triad but arose from either atrium for RA-CS and Sequential. Preshock AF cycle
      lengths were significantly shorter at the earliest activation sites than at seven
      of eight other sites globally distributed over both atria. In all type B
      successful episodes in which one or more rapid activations occurred after the
      shock and in 50 of the 72 failed episodes analyzed, activation fronts spread away
      from the earliest site in a focal pattern, and discrete nonfragmented activation
      complexes were present in the first derivatives of the electrograms. In the other
      22 failed episodes, earliest activation fronts spread in a nonfocal pattern, and
      earliest postshock electrogram derivatives were fractionated. To better interpret
      the activation pattern in the fragmented regions, a 504 electrode plaque with 1.5
      mm electrode spacing was placed on the right atrial appendage in two additional
      sheep. In 11 of 108 failed episodes, earliest postshock activation appeared
      inside the plaque and spread in a focal pattern with nonfragmented electrogram
      derivatives in 10 episodes and in a reentrant pattern with fragmented electrogram
      derivatives in the other. CONCLUSIONS: (1) The electrode configuration influenced
      the location of earliest postshock activation. (2) Earliest postshock activation
      occurred where the preshock AF cycle length was short. (3) Earliest activations
      following all type B successful and most failed episodes were not fragmented and
      spread in a focal pattern. (4) The region of earliest postshock activation in the
      failed episodes without a focal postshock activation pattern exhibited regions of
      fragmented electrogram derivatives that may represent conduction block and
      possibly reentry.

PMID- 15851230
TI  - Ciprofloxacin-induced acquired long QT syndrome.
AB  - Quinolone antibiotics have potentially serious proarrhythmic effects. The effects
      on intracardiac potassium channels result in QT interval prolongation, leading to
      torsades de pointes. Evidence suggests fluoroquinolones cause QT-mediated
      proarrhythmia, and weak evidence links ciprofloxacin with QT-mediated
      arrhythmias. Ciprofloxacin may be given to select patients because the agent is
      believed to be safer than other drugs in its class. We report two cases of
      unexplained cardiac arrest temporally related to ciprofloxacin administration.
      Two female patients (ages 44 and 67 years) developed marked QTc prolongation (QTc
      590 and 680 ms) within 24 hours of ciprofloxacin administration, with recurrent
      syncope and documented torsades de pointes requiring defibrillation. The patients
      previously were stable with sotalol and amiodarone therapy for supraventricular
      arrhythmia without obvious QTc prolongation prior to ciprofloxacin therapy.
      Marked QTc prolongation and subsequent proarrhythmia became a clinical concern
      only after initiation of ciprofloxacin. In both cases, the QTc normalized after
      cessation of ciprofloxacin. Ciprofloxacin may cause QTc prolongation and rarely
      torsades de pointes. This effect is of particular concern in patients with
      predisposing factors, such as concomitant medications or underlying heart disease
      reflecting decreased repolarization reserve.

PMID- 15851231
TI  - How structurally normal are human atria in patients with atrial fibrillation?
AB  - Atrial myocardium in humans shows structural changes that increase with aging.
      The most conspicuous are fibro-fatty replacement and patchy replacement fibrosis.
      The present study reveals that these structural changes are more extensive in
      hearts of patients with paroxysmal atrial fibrillation (AF) than in "no AF"
      hearts. The changes involve the myocardial sleeves on pulmonary veins and sites
      of rapid conduction, such as the terminal crest and Bachmann's bundle. These
      structural changes should be taken into consideration as potential substrates for
      initiation and maintenance of atrial arrhythmias.

PMID- 15851232
TI  - Supraventricular tachycardia in a heart transplant recipient: what is the
      mechanism?

PMID- 15851233
TI  - "Synthetic" ventricular tachycardia.

PMID- 15851234
TI  - S-wave predominance of epicardial electrograms during atrial fibrillation in
      humans: indirect evidence for a role of the thin subepicardial layer.
AB  - OBJECTIVES: The purpose of this study was to characterize the morphology of
      fibrillation electrograms in patients in order to provide insight into the
      underlying electropathologic substrate of atrial fibrillation (AF). BACKGROUND:
      Electrograms recorded during AF show a high degree of spatiotemporal variation.
      METHODS: AF was induced by rapid atrial pacing in 25 patients undergoing cardiac
      surgery. A unipolar mapping array of 244 electrodes was positioned on the free
      wall of the right atrium to record multiple epicardial fibrillation electrograms.
      Local anisotropy in conduction and epicardial wavefront curvature during AF were
      determined by fitting the best quadratic surface on the activation times of
      rectangular areas of 3 x 3 electrodes. RESULTS: During AF, unipolar epicardial
      electrograms revealed a clear predominance of S waves. The average RS difference
      during type I and II AF was -0.15 +/- 0.08 and -0.22 +/- 0.08. During type III
      AF, the predominance of S waves was less prominent (-0.07 +/- 0.05; P < .005). In
      all types of AF, the degree of anisotropy in conduction was remarkably low
      (anisotropy ratio: 1.24 +/- 0.09), and no clear directional effect on the
      relative amplitude of R and S waves was found. There was a weak relationship
      between local curvature of wavefronts and RS difference (r = 0.23; P < .01).
      Computer simulations showed that the negative RS difference could result from
      transmural activation in an epicardial to endocardial direction. CONCLUSIONS: The
      clear predominance of S waves in epicardial fibrillation electrograms is not due
      to anisotropy and can only be partly explained by a high curvature of
      fibrillation waves. Predominant epicardial to endocardial activation seems to be
      important in producing rS electrograms on the epicardium. This finding provides
      indirect evidence that the thin epicardial layer of atrial myocardium plays an
      important role in propagation of fibrillation waves.

PMID- 15851235
TI  - Utility of adenosine 5'-triphosphate in predicting early recurrence after
      successful ablation of manifest accessory pathways.
AB  - OBJECTIVES: The purpose of this study was to determine whether administration of
      adenosine 5'-triphosphate (ATP; 20-40 mg) after successful ablation of accessory
      pathway (AP) with manifest preexcitation is useful for detecting residual
      conduction and predicting early recurrences. BACKGROUND: The reported incidence
      of recurrence of AP conduction after an initially successful procedure is 5% to
      10%. Little information on the variables related to early recurrence has been
      reported. METHODS: We prospectively used 108 ATP tests on 100 consecutive
      patients (66 men, mean age 36 +/- 15 years) with manifest preexcitation. Five
      minutes after successful ablation, intravenous boluses of ATP at increasing doses
      were injected until the target effect of second- or third-degree AV block or AP
      conduction was observed. RESULTS: The effect of ATP was AV block (negative test)
      in 82 cases (76%), conduction over previously ablated AP (positive test) in 9
      cases (8.3%), and no achievement of target effect (nondiagnostic test) in 17
      cases (15.7%). Thirteen early recurrences were observed in 12 patients. In all 9
      (100%) patients with positive ATP test and in 4 (4.9%) of the 82 patients with
      negative ATP test, conduction over the AP recurred (relative risk 20; 95%
      confidence interval 8-53; P < .000001). The diagnostic accuracy of the test
      (analyzing the target effect) was 95%, sensitivity 69%, specificity 100%, and
      positive and negative predictive values 100% and 95%, respectively. CONCLUSIONS:
      ATP administration after successful ablation of APs has a high predictive value
      for early recurrence and may help optimize the duration of the ablation
      procedure.

PMID- 15851236
TI  - Relationship between pattern of occurrence of atrial fibrillation and surface
      electrocardiographic fibrillatory wave characteristics.
AB  - OBJECTIVES: The purpose of this study was to assess whether surface ECG
      fibrillatory (f)-wave characteristics reflect clinical variables, especially
      pattern of occurrence. BACKGROUND: In clinically stable patients, f waves have
      fairly constant quantitative characteristics. Both electrophysiologic and
      structural remodeling might modify f waves. METHODS: We analyzed f waves from 238
      patients (120 men and 118 women; age range 30-97 years, mean 77 +/- 12) with
      atrial fibrillation identified by retrospective chart review as paroxysmal,
      persistent, or permanent fibrillation. Analysis was performed in the time and
      frequency domains on ECGs after QRS-T cancellation. Student's t-test and
      multivariate analysis were used for comparison. RESULTS: The f waves of 12
      patients taking rhythm control drugs had lower frequency ("slower" fibrillation)
      than the f waves of patients not taking such drugs (5.3 +/- 0.6 vs 6.0 +/- 0.7
      Hz, P < .001). Of the 226 remaining patients, 59 were paroxysmal, 30 were
      persistent, and 72 were permanent; 65 had an unknown pattern. Paroxysmal and
      persistent patients were younger than permanent (74 +/- 12 and 72 +/- 15 vs 80 +/
      9 years, P < .002 for both). Paroxysmal, persistent, and permanent patients had
      different f-wave frequencies of 5.7 +/- 0.7, 6.1 +/- 0.8, and 6.2 +/- 0.6 Hz,
      respectively (P = .01 for paroxysmal vs persistent and P < .001 for paroxysmal vs
      permanent). Patients older than 77 years (mean age) had lower f wave frequency
      than those younger 77 years (6.0 +/- 0.7 vs 6.2 +/- 0.7 Hz, P = .01). Using
      multivariate analysis, the overall pattern-frequency relationship was significant
      (p = .014). There was a statistically significant inverse correlation between
      frequency and age (R = .27, slope = -0.017 Hz/year, P < .001). CONCLUSIONS: ECG f
      wave frequency reflects specific clinical variables, with higher frequency in
      permanent than paroxysmal fibrillation but lower frequency in older than younger
      patients. These findings are consistent with the idea that fibrillatory waves are
      modified by both electrophysiologic and structural remodeling.

PMID- 15851237
TI  - Significance of adenosine-induced atrioventricular block in patients with
      unexplained syncope.
AB  - OBJECTIVES: The purpose of this study was to test whether a prolonged (>/=6
      seconds) period of AV block in response to adenosine triphosphate (ATP)
      identifies additional patients at risk for bradycardia who may benefit from
      pacemaker implantation. BACKGROUND: Bradycardia is a common etiology for syncope
      in patients without underlying structural heart disease. Conventional testing
      using electrophysiologic and tilt table studies often fail to identify patients
      prone to episodes of symptomatic bradycardia. METHODS: Adenosine testing was
      performed in 92 consecutive patients (64 women, age 55 +/- 21 years) with syncope
      of uncertain origin referred for tilt table testing. The adenosine test measured
      the maximal R-R interval after bolus administration of intravenous adenosine 150
      mug/kg to upright patients. A positive adenosine AV block response was defined as
      a maximal R-R interval > or =6 seconds. RESULTS: A total of 21 patients (23%) had
      a positive response. During mean follow-up of 14.3 +/- 5.9 months, 14 patients
      (16%) had recurrent syncope. Among patients with a positive adenosine response, 3
      patients (14%) had recurrent syncope. In comparison, 11 of 69 patients (16%)
      without adenosine-induced AV block had recurrent syncope (P = 1.00). CONCLUSIONS:
      Prolonged adenosine-induced AV block in patients with unexplained syncope failed
      to predict recurrent syncopal episodes. These data do not support therapeutic
      interventions (e.g., pacemaker implantation) based on a positive adenosine AV
      block response alone.

PMID- 15851238
TI  - Inhibition of angiotensin II signaling and recurrence of atrial fibrillation in
      AFFIRM.
AB  - OBJECTIVES: We investigated whether inhibition of endogenous angiotensin II
      signaling reduces the recurrence rate of atrial fibrillation (AF) in patients
      enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management
      (AFFIRM) study. BACKGROUND: Structural and electrical remodeling contribute to
      AF. Previous experimental studies have implicated the angiotensin II signaling
      pathway in this process, and recent clinical evidence supports a beneficial
      effect of inhibiting angiotensin II activity. METHODS: Using the AFFIRM database,
      we retrospectively identified a cohort of patients randomized to the rhythm
      control arm who were in sinus rhythm. Exposure to angiotensin II receptor
      blockers or angiotensin-converting enzyme inhibitors (ANGI) was determined, and
      the time to first recurrence of AF was compared between ANGI users and nonusers.
      RESULTS: The study cohort included 732 patients not taking ANGI through the
      initial 2-month follow-up and 421 patients taking ANGI during this time. Patients
      in the ANGI group more likely had hypertension, diabetes, coronary artery
      disease, and congestive heart failure compared to patients not taking ANGI. Risk
      of AF recurrence in the ANGI treatment group did not differ from the risk
      observed in patients not taking the drugs (hazard ratio [HR] = 0.91, 95%
      confidence interval [CI] = 0.77-1.09). However, in patients with congestive heart
      failure or impaired left ventricular function, ANGI use was associated with a
      lower risk of AF recurrence. CONCLUSIONS: This analysis provides evidence that
      ANGI use may be beneficial in some patient subgroups with AF and underscores the
      need for randomized clinical trials defining more fully the role of angiotensin
      II inhibition in treating AF.

PMID- 15851239
TI  - Late recurrent arrhythmias after ablation of atrial fibrillation: incidence,
      mechanisms, and treatment.
AB  - OBJECTIVES: The aim of the study was to determine the incidence of atrial flutter
      and other arrhythmia recurrences (other than atrial fibrillation [AF]) during
      long-term follow-up after left atrial substrate modification by percutaneous
      radiofrequency (RF) ablation of AF. BACKGROUND: RF ablation is an effective
      treatment for patients with AF. However, late recurrent arrhythmias may
      complicate the patient's course. METHODS: One hundred fifty consecutive patients
      with paroxysmal or persistent AF were included in this prospective study. The
      incidence of arrhythmia recurrences after AF ablation was analyzed during long
      term follow-up using repetitive 7-day ECG recording. RESULTS: In 28 of 150
      patients (18.7%), stable regular arrhythmias other than AF were detected during
      follow-up. Left atrial flutter observed in 10 patients (6.7%) was treated by
      recompletion of the ablation lines in all 10 patients. Left atrial flutter was
      associated with recurrence of AF in all 10 patients. Nine of 10 patients (90%)
      were free from atrial flutter and 6 of 10 patients were free from AF after the
      second intervention. Typical right atrial flutter occurred in 10 patients (6.7%)
      and was treated successfully by percutaneous RF ablation without recurrence in
      all patients. Additionally, atrial flutter was documented during follow-up in 7
      patients (4.7%); however, invasive electrophysiologic evaluation was not
      performed due to various reasons. CONCLUSIONS: Left atrial flutter is a relevant
      complication after RF catheter ablation of AF and was always associated with AF
      recurrence in our study population. Prevention of left atrial flutter can be
      achieved by induction of ablation lines as continuous and transmural as possible.
      However, left atrial flutter that does occur late after ablation is amenable to
      interventional treatment with good prospects of success.

PMID- 15851240
TI  - Epicardial but not endocardial premature stimulation initiates ventricular
      tachyarrhythmia in canine in vitro model of long QT syndrome.
AB  - OBJECTIVES: To explore the mechanism, we tested the hypothesis that premature
      epicardial stimulation transiently increased the dispersion of repolarization
      leading to VT. BACKGROUND: Premature stimulation initiated ventricular
      tachycardia (VT) when applied to the epicardium but not to the endocardium in a
      canine model of long QT syndrome (LOTS). METHODS: We optically mapped action
      potentials (APs) on the cut-exposed transmural surfaces of isolated wedges of
      canine ventricular walls perfused with anemone toxin II (ATX-II), which produced
      type 3 LQTS with an asymmetrical transmural profile of repolarization that was
      earliest in the epicardium and latest in deep subendocardium. RESULTS: Earliest
      excitable epicardial stimulation triggered VT in 5 of 18 wedges receiving > or =5
      nmol/L ATX-II by direct activation of epicardium, which delayed repolarization in
      the still refractory midmyocardium and further enhanced the dispersion of
      repolarization. These VTs were initiated 197 +/- 72 ms (n = 10) after the
      premature stimulation, from focal regions of earliest repolarization downstream
      to the steepest local spatial gradients of repolarization, and maintained by new
      focal activation and reentry. Transmural differences in the cycle lengths of
      activations altered conduction pathways and resulted in torsades de pointes-like
      polymorphic VT. In contrast, VTs were not initiated by endocardial stimulation at
      the same premature intervals or when ATX-II was < or =2.5 nmol/L. Failed VT
      initiation was associated with significantly lower maximum local gradient of
      repolarization. CONCLUSIONS: Heterogeneic repolarization in LQTS provides a
      transmural asymmetrical substrate for the earliest excitable epicardial, but not
      endocardial, stimulation to further delay midmyocardial repolarization and
      produce a steep spatial gradient of repolarization potential initiating torsades
      de pointes-like polymorphic VT.

PMID- 15851241
TI  - Cardiac vulnerability to electric shocks during phase 1A of acute global
      ischemia.
AB  - OBJECTIVES: The purpose of this study is to characterize the changes in
      vulnerability to electric shocks during phase 1A of global ischemia in the rabbit
      ventricles and to determine the mechanisms responsible for these changes.
      BACKGROUND: Mechanisms responsible for the changes in cardiac vulnerability over
      the course of ischemia phase 1A remain poorly understood. The lack of
      understanding results from the rapid ischemic change in cardiac
      electrophysiologic properties, which renders experimental evaluation of
      vulnerability difficult. METHODS: To examine dynamic changes in vulnerability to
      electric shocks over the course of acute global ischemia phase 1A, this study
      used a three-dimensional anatomically accurate bidomain model of ischemic rabbit
      ventricles. Monophasic shocks are applied at various coupling intervals to
      construct vulnerability grids in normoxia and at various stages of ischemia phase
      1A. RESULTS: Our simulations demonstrate that 2 to 3 minutes after the onset of
      ischemia, the upper limit of vulnerability remains at its normoxic value (12.75
      V/cm); however, arrhythmias are induced at shorter coupling intervals. As
      ischemia progresses, the upper limit of vulnerability decreases, reaching 6.4
      V/cm in the advanced stage of ischemia phase 1A, and the vulnerable window shifts
      towards longer coupling intervals. CONCLUSIONS: Changes in the upper limit of
      vulnerability result from an increase in the spatial extent of the shock-end
      excitation wavefronts and the slower recovery from shock-induced positive
      polarization. Shifts in the vulnerable window stem from decreases in local
      repolarization times and the occurrence of postshock conduction failure caused by
      prolonged postrepolarization refractoriness.

PMID- 15851242
TI  - Developmental evolution of the delayed rectifier current IKs in canine heart
      appears dependent on the beta subunit minK.
AB  - OBJECTIVES: We tested the hypothesis that the developmental changes occurring in
      I(Kr) and I(Ks) can be explained by changes in the expression of ERG encoding
      I(Kr), and KCNQ1, the beta subunit minK, and the recently reported subunit FHL2
      encoding I(Ks). BACKGROUND: The delayed rectifier current contributes importantly
      to the developmental evolution of the canine myocardial action potential.
      Specifically, in left ventricular epicardial myocytes, I(Ks) is absent and I(Kr)
      is the major repolarizing current until age 4 weeks. With subsequent development,
      I(Ks) density increases and I(Kr) decreases, resulting in an altered voltage-time
      course of repolarization. METHODS: We used Western blotting and real-time
      polymerase chain reaction to compare the expression of ERG, KCNQ1, minK, and FHL2
      in 1-week-old pups and adult dogs. RESULTS: ERG levels are high at 1 week and
      decrease significantly with age, consistent with developmental decrease in I(Kr).
      Whereas expression of KCNQ1 and FHL2 is unchanged between the two age groups,
      minK is minimally expressed at 1 week and increases in adults, consistent with
      developmental increase in I(Ks). CONCLUSIONS: A reduction in ERG explains the
      developmental decrease in I(Kr), whereas the accessory subunit minK appears to be
      the critical determinant of developmental evolution of I(Ks).

PMID- 15851243
TI  - Nerve sprouting induced by radiofrequency catheter ablation in dogs.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that
      radiofrequency (RF) catheter ablation results in cardiac nerve sprouting.
      BACKGROUND: Nerve sprouting plays a role in cardiac arrhythmogenesis. Whether or
      not nerve sprouting occurs after RF catheter ablation is unclear. METHODS: We
      performed RF catheter ablation in the right atrium (RA) and right ventricle (RV)
      in 10 dogs, which then were sacrificed in 2 hours (acute group, n = 5) or 1 month
      (chronic group, n = 5). Seven normal dogs were used as control.
      Immunohistochemical staining for growth-associated protein 43 (GAP-43) was
      performed to measure growing (sprouting) nerves. RESULTS: A significant increase
      of GAP-43 immunoreactive nerve fiber density was observed at the RA ablation
      sites in 2 hours (4,410 +/- 1,379 microm(2)/mm(2)) and in 1 month (2,948 +/- 666
      microm(2)/mm(2)) after ablation compared to controls (1,377 +/- 471
      microm(2)/mm(2), P = .0001). At remote sites (>2 cm away from ablation sites) of
      RA, RF ablation also resulted in robust nerve sprouting in both the acute group
      (5,846 +/- 3241 microm(2)/mm(2)) and the chronic group (6,030 +/- 2226
      microm(2)/mm(2)). RF ablation in the RV did not increase nerve density at the
      ablation sites, but nerve density was increased at remote sites in 2 hours (1,345
      +/- 451 microm(2)/mm(2), P = .0136) that was reduced down to the normal control
      level (722 +/- 337 microm(2)/mm(2)) in 1 month. CONCLUSIONS: Nerve sprouting
      occurred within 2 hours after RF ablation in both the RA and RV and persisted for
      at least 1 month in the RA but not the RV. The increased GAP-43(+) nerve
      densities developed at both the ablation and the remote sites.

PMID- 15851244
TI  - Can radiofrequency ablation get on your nerves?

PMID- 15851245
TI  - Pauses after burst pacing provoke afterdepolarizations and torsades de pointes in
      a patient with long QT syndrome.
AB  - A patient with long QT syndrome and syncope underwent electrophysiological
      testing and recording of monophasic action potentials (MAP). Programmed
      ventricular stimulation using up to three premature stimuli did not provoke
      arrhythmias. Transient action potential prolongation and afterdepolarizations
      were observed during pauses directly after high-rate fix frequent right
      ventricular burst pacing at 120-160 bpm. During the pause after burst pacing at
      180 bpm, afterdepolarizations at 16-19% amplitude of the MAP plateau persisted
      for several beats and preceded a short episode of torsades de pointes. High-rate
      burst pacing provoked afterdepolarizations and triggered torsades de pointes in
      this patient with long QT syndrome.

PMID- 15851246
TI  - Mahaim fiber: an atriofascicular or a long atrioventricular pathway?
AB  - There is debate concerning the distal insertion of Mahaim fibers. Some findings
      favor an atriofascicular fiber connected with the distal right bundle branch.
      Other findings favor a long atrioventricular (AV) structure inserting into the
      myocardium. A patient having a decrementally conducting accessory pathway is
      reported. Proximal and distal Mahaim potentials were recorded during sinus
      rhythm, atrial pacing, and antidromic tachycardia. Both proximal and distal M
      potentials always preceded the QRS complex during sinus rhythm and antidromic
      tachycardia earlier than the right bundle branch potential. During tachycardia,
      the distal M potential was recorded 6 ms before the retrograde right bundle
      potential. Other arguments consistent with an AV connection were a change in the
      QRS configuration during tachycardia after the first radiofrequency pulse at the
      site of the distal M potential and absence of right bundle branch block after
      successful ablation. Conduction through the proximal part of the Mahaim fiber was
      unaltered after ablation, as assessed by recording the proximal M potential.
      Electrophysiologic evidence is presented suggesting a long AV accessory pathway
      inserting close to the distal right bundle branch rather than an atriofascicular
      connection in this patient with a Mahaim fiber.

PMID- 15851247
TI  - Absent ventricular tachycardia detection in a biventricular implantable
      cardioverter-defibrillator due to intradevice interaction with a rate smoothing
      pacing algorithm.
AB  - A biventricular implantable cardioverter-defibrillator failed to detect
      monomorphic ventricular tachycardia (VT) with a cycle length that was within the
      programmed VT detection zone. VT beats were undetected because they fell within
      the atrial-paced ventricular blanking period while a rate smoothing pacing
      algorithm was turned on. This problem can occur with slow VT, a short AV delay,
      and a low upper tracking rate without any device interaction warning. This
      intradevice interaction can lead to untreated episodes of VT and result in
      recurrent episodes of heart failure and even death in patients with reduced left
      ventricular function and chronic heart failure.

PMID- 15851248
TI  - Heart rate turbulence: a 5-year review.
AB  - April 2004 marks the fifth anniversary of the first heart rate turbulence (HRT)
      publication, which demonstrated the usefulness of HRT in predicting cardiac death
      in postmyocardial infarction patients. Since then, HRT has been shown to predict
      prognosis of patients with dilated cardiomyopathy and of patients with heart
      failure of mixed etiology. HRT also has been shown to be predictive even in the
      current lower-mortality era of acute revascularization therapy for myocardial
      infarction. We discuss the latest criteria for obtaining reliable measurements of
      HRT, review factors that influence HRT values, and consider recent clinical
      studies.

PMID- 15851249
TI  - Intravascular pacemaker and defibrillator lead extraction: a state-of-the-art
      review.

PMID- 15851250
TI  - Conduction, gap junctions, and atrial fibrillation: an eternal triangle?

PMID- 15851251
TI  - Wide QRS complexes during atrial fibrillation: what is the mechanism?

PMID- 15851252
TI  - Isorhythmic interaction between a dual-chamber pacemaker and an intrinsic rhythm:
      pacemaker malfunctioning or not?
AB  - A patient underwent cardiac surgery (including a biatrial maze procedure) for
      congenital heart disease and paroxysmal atrial tachycardia. Previously, a dual
      chamber pacemaker was inserted for bradycardia. Postoperative ECG showed a narrow
      complex rhythm interspersed with pacing stimuli that appeared premature and
      unable to capture. The phenomenon was due to isorhythmic interaction between the
      pacemaker and the patient's own intrinsic rhythm, which is compatible with normal
      pacemaker functioning. The different patterns possible for the phenomenon and the
      necessary conditions for their occurrence are elucidated.

PMID- 15851253
TI  - Optimizing the defibrillation vector with a right-sided implantable cardioverter
      defibrillator.

PMID- 15851254
TI  - Practice or research--patient or participant: is there a difference?

PMID- 15851255
TI  - Electrocardiogram in patients with fasciculoventricular pathways: a comparative
      study with anteroseptal and midseptal accessory pathways.
AB  - OBJECTIVES: The purpose of this study was to describe the ECG profile of a cohort
      of patients with fasciculoventricular pathways and compare the profile with the
      ECG of patients with anteroseptal and midseptal accessory pathways. BACKGROUND:
      Electrophysiologic findings suggest fasciculoventricular pathways insert into the
      septal region. Findings also suggest the 12-lead surface ECG during sinus rhythm
      is similar to the ECG of patients with anteroseptal and midseptal bypass tracts.
      METHODS: Four different observers analyzed the 12-lead ECG of seven patients with
      fasciculoventricular pathways (group I) and the ECG of 20 patients with midseptal
      AV accessory pathways (group II) and 20 patients with anteroseptal AV accessory
      pathways (group III). The following variables were analyzed: ECG frontal plane
      QRS and delta wave axis; angle between the QRS and the delta wave axis; QRS
      width; R/S ratio in lead III; presence of a negative delta wave in inferior
      leads; and precordial lead transition to R/S >1. RESULTS: The ECG of
      fasciculoventricular pathways shows a variable pattern. It shares some features
      with an anteroseptal accessory pathway and others with a midseptal accessory
      pathway. A narrower QRS width was the most important variable in distinguishing a
      fasciculoventricular pathway from a septally located AV bypass tract (P <.0001).
      The angle between the QRS and the delta wave frontal plane axis could
      differentiate a fasciculoventricular pathway from an anteroseptal bypass tract (P
      <.0001) but not from a midseptal accessory pathway. CONCLUSIONS: The sinus rhythm
      ECG of patients with fasciculoventricular pathways shows similarities with ECGs
      of patients with anteroseptal and midseptal accessory pathways, but the QRS
      complex usually is narrower. The ECG recorded during sinus rhythm cannot reliably
      differentiate fasciculoventricular pathways with a broad QRS complex from
      anteroseptal or midseptal bypass tracts.

PMID- 15851256
TI  - "Mahaim" fasciculoventricular fibers: rare variant of ventricular preexcitation
      or subtle clinical problem?

PMID- 15851257
TI  - Rescue ablation of electrical storm in patients with ischemic cardiomyopathy: a
      potential-guided ablation approach by modifying substrate of intractable,
      unmappable ventricular tachycardias.
AB  - OBJECTIVES: The purpose of this study was to evaluate a substrate-modifying,
      primarily potential-guided catheter ablation approach as a bailout therapy in
      patients with complex myocardial infarction and electrical storms due to
      ventricular tachycardias (VTs). BACKGROUND: Management of electrical storm is a
      domain of medical treatment. A definite trigger or delineated scar has been
      characterized as a requirement for substrate-orientated ablation of intractable
      unmappable ventricular tachyarrhythmias but can be absent, as shown in the
      presented cases. METHODS: Five patients who presented with ischemic
      cardiomyopathy and severe reduced left ventricular ejection fraction also
      suffered from multiple types of unstable VTs that deteriorated into drug
      refractory electrical storm. Patients had 96 to 580 VT episodes requiring therapy
      with an implantable cardioverter-defibrillator (ICD) and received 3 to 310 shock
      deliveries prior to ablation. Treatment with beta-blockers, amiodarone, class IB
      antiarrhythmic drugs, deep sedation, and overdrive pacing and/or cardioversion of
      incessant VTs failed to stabilize the electrical storm but enabled left
      ventricular electroanatomic voltage mapping. A simplified substrate modification
      was performed by ablation of delayed fractionated potentials in areas identified
      by pace mapping, matching three to eight documented types of VTs per patient in
      complex scar areas. RESULTS: All patients could be stabilized after ablation.
      During 12 to 30 months of follow-up, three patients remained free of any VT
      episode requiring ICD treatment, and two patients had <1 VT episode per month.
      CONCLUSIONS: The cases presented demonstrate that rescue VT ablation of drug
      refractory electrical storm is possible by a substrate-orientated ablation
      approach even in patients with complex chronic infarction and various VTs.

PMID- 15851258
TI  - Electrophysiologic interventions in patients with inferior vena cava filters:
      safety and efficacy of the transfemoral approach.
AB  - OBJECTIVES: The purpose of this study was to evaluate the transfemoral venous
      approach for electrophysiologic interventions in patients with inferior vena cava
      filters. BACKGROUND: Reports have detailed complications associated with
      obtaining central venous access in patients with inferior vena cava filters.
      Accordingly, electrophysiologic interventions have been modified or deferred
      altogether in such patients. METHODS: Patients requiring interventions with a
      transfemoral approach who were at least 3 months post filter insertion underwent
      fluoroscopically guided insertion and withdrawal of electrode catheters with
      appropriate follow-up. RESULTS: Five patients underwent successful pacing,
      electrophysiologic study, or radiofrequency ablation using one to three
      catheters, with no complications attributable to filter placement. CONCLUSIONS:
      Transfemoral electrophysiologic interventions can be safely undertaken across
      vena cava filters provided appropriate precautions are taken.

PMID- 15851259
TI  - Effect of rate and rhythm control on left ventricular function and cardiac
      dimensions in patients with persistent atrial fibrillation: results from the RAte
      Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE)
      study.
AB  - OBJECTIVES: The purpose of this study was to evaluate left ventricular function
      and atrial and ventricular diameters in patients with persistent atrial
      fibrillation (AF) treated with rate or rhythm control. BACKGROUND: Restoration of
      sinus rhythm in patients with persistent AF may improve left ventricular function
      and reduce atrial dimensions. Adequate rate control in AF may preserve
      ventricular function. METHODS: In 335 patients included in the RAte Control
      versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study,
      echocardiography was performed at baseline and 1- and 2-year follow-up.
      Echocardiography was compared between patients randomized to rate control (n =
      160) and rhythm control (n = 175). In the rhythm control group, echocardiography
      was compared between patients with AF versus sinus rhythm at study end.
      Multivariate analysis was performed to determine parameters related to
      improvement of left ventricular function and increase of atrial diameters.
      RESULTS: Fractional shortening improved significantly under rate and rhythm
      control (31 +/- 10% at baseline to 33 +/- 9% at 2 years, and from 30 +/- 10% to
      34 +/- 9%; both P < .05, respectively). Under rate control, left and right atrial
      size increased significantly compared to baseline. Under rhythm control, only
      left atrial size increased. Multivariate analysis revealed that only sinus rhythm
      at study end was associated with an increase of fractional shortening. AF at
      study end, hypertension, and no use of angiotensin-converting enzyme inhibitors
      were independently associated with increase in atrial size. CONCLUSIONS: Routine
      rate control prevents deterioration of left ventricular function. Maintenance of
      sinus rhythm is associated with improvement of left ventricular function and
      reduction of atrial sizes.

PMID- 15851260
TI  - Effect of atrial fibrillation on chamber dimensions.

PMID- 15851261
TI  - Temporal characteristics of cardiac memory in humans: vectorcardiographic
      quantification in a model of cardiac pacing.
AB  - OBJECTIVES: The purpose of this study was to assess the temporal characteristics
      of cardiac memory in a human pacing model. BACKGROUND: Cardiac memory is induced
      by periods of altered ventricular activation and in the canine pacing model
      develops in 2 to 3 weeks. METHODS: Cardiac memory development (phase 1) and
      resolution (phase 2) was followed qualitatively (ECG) and quantitatively
      (vectorcardiography [VCG]) in 20 patients with symptomatic sinus bradycardia
      receiving DDD-R pacing at physiologic rates. During phase 1, maximum ventricular
      pacing in the right ventricular apical endocardium was achieved by short AV
      delay. ECG and VCG were recorded during normal ventricular activation prior to
      implantation (sinus rhythm), 1 day after and then weekly for 5 to 8 weeks during
      AAI pacing (n = 14, "long-term"), and daily during 1 week (n = 6, "short-term").
      In phase 2, the remaining cardiac memory was related to the amount of ventricular
      pacing. A long AV delay was chosen to reduce ventricular pacing, and 14 patients
      were seen once after 4 to 5 weeks. RESULTS: ECG and VCG showed marked changes in
      all patients within 1 week's pacing and remained stable during phase 1. Of the 14
      long-term patients, 13 showed significant change in T vector azimuth (mean -150
      degrees ) and 11 in T vector elevation (mean 63 degrees ). At the end of phase 2,
      a linear relation existed between remaining cardiac memory (%) and amount (%) of
      delivered ventricular pacing. CONCLUSIONS: Cardiac memory developed and reached
      steady state within 1 week of right ventricular endocardial pacing at physiologic
      rates in man, was preserved in proportion to delivered ventricular pacing, and
      completely resolved within 1 month in its absence.

PMID- 15851262
TI  - The heart does not forget.

PMID- 15851263
TI  - Systematic evaluation of the determinants of defibrillation efficacy.
AB  - OBJECTIVES: We studied the effect of varying shock capacitance, shock impedance,
      and pulse duration on defibrillation efficacy in a randomized, crossover manner
      for biphasic shocks. BACKGROUND: The relationship between the electrical
      determinants of defibrillation efficacy is incompletely understood. METHODS:
      Biphasic shocks were delivered to 12 dogs through epicardial patches (to vary
      impedance) after 15 seconds of ventricular fibrillation using one of 100- or 155
      muF capacitors at each of four pulse durations (2.5, 5, 10, 20 ms), in a balanced
      random order. There were two impedance groups: six with higher impedance (mean 97
      +/- 15 Omega, range 80-120) and six with lower impedance (mean 39 +/- 3 Omega,
      range 34-44). Voltage requirements were estimated as the average of three
      defibrillation threshold (DFT) tests. RESULTS: Shock capacitance, resistance, and
      pulse duration all had significant effects upon the minimum voltage DFT (P =
      .0065, P = .0066, and P = .0001, respectively). The tilt associated with the
      lowest voltage and current requirement for each of the four
      capacitance/resistance combinations varied widely, between 34 +/- 5% and 63 +/-
      3%, depending on capacitance and impedance. The optimal pulse duration associated
      with minimum DFT lies between 5.11 and 5.34 ms. CONCLUSIONS: Defibrillation
      voltage requirements for biphasic shocks are affected by pulse duration,
      capacitance and impedance, but not "tilt."

PMID- 15851264
TI  - Safety and efficacy of circumferential pulmonary vein catheter ablation of atrial
      fibrillation.
AB  - OBJECTIVES: The purpose of this study was to report the safety, efficacy, and
      predictors of recurrence of circumferential pulmonary vein (PV) catheter ablation
      in patients with atrial fibrillation (AF). BACKGROUND: Circumferential PV
      ablation has been described as an alternate ablation strategy for AF. METHODS:
      Seventy consecutive patients (age 56 +/- 10 years) with symptomatic drug
      refractory paroxysmal (n = 21), persistent (n = 22), and permanent (n = 27) AF
      underwent catheter ablation. The catheter ablation procedure was performed by
      creating circular lesions encircling right- and left-side PV ostia guided by an
      electroanatomic (CARTO) mapping system. Linear ablation lesions also were created
      in the cavotricuspid isthmus, the mitral isthmus, and in the posterior left
      atrium. In 42 patients (60%), additions linear lesions were created between
      superior and inferior PVs in a "figure-of-eight" fashion. RESULTS: At 6 +/- 2.5
      months of follow-up, 53 patients (76%) were AF free, including 39 patients (56%)
      not taking and 14 patients (20%) taking antiarrhythmic drugs. Among various
      variables, only early recurrence of AF was a predictor of long-term recurrence.
      Significant complications included one pericardial tamponade, one stroke, and two
      PV occlusions. Both patients with PV occlusion received radiofrequency delivery
      in a figure-of-eight fashion. CONCLUSIONS: Circumferential PV catheter ablation
      of AF is associated with moderate efficacy and risk of complications. The absence
      of a difference in efficacy combined with the risk of PV stenosis associated with
      figure-of-eight lesion lead us to conclude that the figure-of-eight lesion should
      not be a routine component of circumferential PV AF ablation procedures.

PMID- 15851265
TI  - Clinical predictors of atrial defibrillation thresholds with a dual-coil, active
      pectoral lead system.
AB  - OBJECTIVES: The purpose of this study was to identify clinical predictors of
      atrial defibrillation thresholds (DFTs) with standard implantable cardioverter
      defibrillator (ICD) leads. BACKGROUND: Atrial defibrillation can be achieved with
      active pectoral, dual-coil transvenous ICD lead systems. If clinical predictors
      of atrial defibrillation efficacy with these lead systems were identified, they
      could be used to predict which patients may require more complex lead systems for
      atrial defibrillation, such as a coronary sinus electrode. METHODS: This was a
      prospective study of 135 consecutive patients undergoing initial ICD implant for
      standard indications. The lead system evaluated was a transvenous defibrillation
      lead with coils in the superior vena cava (SVC) and right ventricular apex (RV),
      and a left pectoral pulse generator emulator (CAN). The shocking pathway was RV-
      >SVC+CAN. Atrial DFT was measured using a step-up protocol. Clinical and
      echocardiographic parameters were evaluated as predictors of atrial DFT and
      multiple linear regression was performed. RESULTS: Mean atrial DFT was 4.6 +/-
      3.8 J. Atrial DFT was < or =3 J in 70 patients (52%) and < or = 10 J in 97% of
      patients. The highest atrial DFT was 20 J (one patient). Left atrial size (r =
      0.21, P = .01) and left ventricular end-diastolic diameter (r = 0.19, P = .02)
      were independent predictors of atrial DFT. However, these two predictors
      accounted for only 6% of the variability in atrial DFT. CONCLUSIONS: Clinical
      parameters are of limited use in predicting atrial DFT with a dual-coil, active
      pectoral ICD lead system. Because the RV--> SVC + CAN shocking pathway provides
      reliable atrial and ventricular defibrillation, this configuration should be
      preferred for combined atrial and ventricular ICDs.

PMID- 15851266
TI  - Feasibility and validation of registration of three-dimensional left atrial
      models derived from computed tomography with a noncontact cardiac mapping system.
AB  - OBJECTIVES: The purpose of this study was to determine the feasibility and assess
      the validity of registering three-dimensional (3D) models from computed
      tomographic (CT) images using a cardiac mapping system. BACKGROUND: Registration
      of 3D anatomic models with an interventional system could help identify and
      navigate mapping and ablation catheters over a complex structure such as the left
      atrium (LA). METHODS: ECG-gated, contrast-enhanced cardiac CT imaging was
      performed in 14 patients with atrial fibrillation. Segmentation was used to
      create 3D models of the LA. The 3D models were registered with the mapping system
      using a series of fiducial points. Registration was accomplished retrospectively
      in the first 10 patients, and catheter navigation was visualized from recorded
      data. In the final four patients, registration was accomplished in real time
      during electrophysiologic study. The mapping catheter position, as it was
      navigated inside the LA, was applied to the registered model in real time. For
      the validation study, temporary pacing leads were implanted in the LA of 10 dogs.
      Following this, CT scanning, segmentation, LA model importation, and registration
      was described previously. After registration, a mapping catheter was positioned
      at the site of each buried lead according to the registered model with no
      fluoroscopic guidance. A radiofrequency lesion was created at this location, and
      the dog was sacrificed, the heart removed and stained, and the distance between
      the buried lead and the lesion measured. RESULTS: During the feasibility study,
      the location of the catheter in the registered model correlated with fluoroscopy,
      angiography, and intracardiac electrograms. LA endocardial potentials during
      sinus rhythm and any premature atrial contractions also were successfully
      delineated over the registered models. In the validation study, the mean target
      registration error was 2.0 +/- 3.6 mm. CONCLUSIONS: Registration of CT-derived 3D
      models of the LA using a cardiac mapping system is feasible and accurate.

PMID- 15851267
TI  - Ablation of atrial tachycardia after surgery for congenital and acquired heart
      disease using an electroanatomic mapping system: Which circuits to expect in
      which substrate?
AB  - OBJECTIVES: The purpose of this study was to compare atrial tachycardia circuits
      after a range of cardiac operations. BACKGROUND: Knowledge of circuits occurring
      in a given postsurgical substrate should help to ablate these challenging
      tachycardias and develop potential preventive strategies. METHODS: We analyzed
      tachycardia circuits in 83 consecutive patients (60 males; median age 47 years,
      range 9-73) after atrial incisions undergoing ablation of atrial tachycardias. A
      combined strategy of electroanatomic (CARTO) and entrainment mapping was used.
      Fifty-two patients (63%) underwent operation for congenital and 31 (37%) for
      acquired heart disease. Patients were divided into subgroups based on the
      intervention performed in the atria: right lateral atriotomy (39 patients), left
      atrial (11) and superior transseptal (10) approach to the mitral valve, biatrial
      heart transplantation (8), Mustard (8) and Fontan (4) procedure, and other
      interventions (3). RESULTS: Most of the 119 tachycardias mapped were isthmus
      dependent atrial flutter (66) and incisional tachycardia (30). Isthmus-dependent
      atrial flutter was the most frequent arrhythmia in all subgroups except for
      Fontan patients, in whom incisional tachycardia was most frequent. The
      distribution of tachycardia circuits did not differ significantly among groups.
      CONCLUSIONS: The observed circuits did not differ among the postsurgical
      substrates. Isthmus-dependent atrial flutter should be the first circuit
      considered in patients after atrial incisions.

PMID- 15851268
TI  - Spatial QRS-T angle predicts cardiac death in a clinical population.
AB  - OBJECTIVES/BACKGROUND: The purpose of this study was to validate the prognostic
      value of computer-derived measurements of the spatial alignment of ventricular
      depolarization and repolarization from the standard 12-lead ECG in a general
      medical population. METHODS: Analyses were performed on the first ECG digitally
      recorded from 46,573 consecutive patients since 1987. QRS and T vector were
      synthesized by deriving XYZ leads from the 12 leads using the inverse Dower
      weighting matrix. Subset analyses were considered in patients with and those
      without standard ECG diagnoses (i.e., atrial fibrillation, Q waves, left
      ventricular hypertrophy, prolonged QRS duration). The main outcome measure was
      cardiovascular mortality. RESULTS: During a mean follow-up of 6 years, 4,127
      cardiovascular deaths occurred. After adjusting for age, heart rate, and gender
      in a Cox regression analysis, spatial QRS-T angle was the most significant
      predictor of cardiovascular mortality, outperforming all other ECG measurements
      and diagnostic statements. In the subset with ECGs free of any standard
      diagnoses, annual cardiovascular mortality was 0.8% for normal (0-50 degrees ),
      2.3% for borderline (50-100 degrees ), and 5.1% for abnormal (100-180 degrees )
      QRS-T angle groups. The borderline and abnormal angle groups had 1.5- and 1.9
      fold higher risk, respectively, relative to the normal QRS-T angle group after
      adjustment for age, gender, and heart rate. Similar results were found when
      patients with standard ECG diagnosis were included or compared. CONCLUSIONS:
      Spatial QRS-T angle is a significant and independent predictor of cardiovascular
      mortality that provides greater prognostic discrimination than any of the
      commonly utilized ECG diagnostic classifications.

PMID- 15851269
TI  - Repolarization morphology in standard short-term electrocardiogram and cardiac
      risk stratification.

PMID- 15851270
TI  - Safety and efficacy of epicardial cryoablation in a canine model.
AB  - OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of
      cryoablation in a closed chest canine epicardial ablation model. BACKGROUND:
      Limitations of radiofrequency energy in the epicardial space warrants
      investigation of alternative energy sources. METHODS: A linear-tip catheter with
      a 3-cm freezing element and a 6-mm-tip catheter were used to create epicardial
      atrial and ventricular cryolesions. Epicardial coronary arteries were targeted to
      evaluate the effects of cryoablation on epicardial vessels. Cryoablation was
      performed at -90 degrees C for 4 minutes per lesion. Pathologic examination of
      the hearts was performed. Lesions were stained with tetrazolium chloride,
      analyzed grossly, and examined histologically. RESULTS: Ten of 11 linear catheter
      atrial lesions were transmural (average depth 1.5 +/- 1.3 mm). Only three of 13 6
      mm-tip atrial lesions were transmural (average depth 1.1 +/- 1.2 mm). Ventricular
      lesions were continuous and not transmural (average depth of lesion for the
      linear and 6-mm-tip catheters: 2.7 +/- 1.3 mm and 1.6 +/- 0.7 mm, respectively).
      Angiographic stenosis (20-100%) during freezing was detected in 9 of 28 lesions,
      with TIMI III flow present in all vessels 5 minutes following thaw. Neointimal
      proliferation was present in 13 vessels, with no evidence of damage in vessels
      with internal diameters greater than 0.7 mm. Occlusive injury was identified in
      one small branch vessel. CONCLUSIONS: Creation of transmural lesions was possible
      in the atria but not in the ventricles. Cryothermal ablation can cause neointimal
      proliferation, with the probability that damage will be directly proportional to
      lesion depth and inversely proportional to vessel diameter.

PMID- 15851271
TI  - To freeze or burn the epicardium?

PMID- 15851272
TI  - Atypical access to typical atrial flutter.
AB  - Typical atrial flutter with reentry around the tricuspid valve can easily be
      cured by ablating the cavotricuspid isthmus. In the reported case, transvenous
      access to the tricuspid valve was not possible because of a total cavopulmonal
      connection in congenital mitral atresia. Successful angioplasty of a small
      fenestration between the total cavopulmonal connection and the genuine right
      atrium (RA) allowed anterograde transvenous access to the RA. Electroanatomic RA
      mapping confirmed peritricuspid reentry, and successful ablation was performed.

PMID- 15851273
TI  - Spontaneous onset of ventricular fibrillation in Brugada syndrome with J wave and
      ST-segment elevation in the inferior leads.
AB  - We report the case of a 52-year-old man with variant Brugada syndrome who was
      successfully resuscitated from ventricular fibrillation (VF). Resting ECG showed
      J wave and ST-segment elevation in the inferior leads but no coved or saddleback
      ST-segment elevation in the right precordial leads. Pilsicainide infusion
      provoked coved-type ST-segment elevation in the right precordial leads and mild
      ST-segment elevation 80 ms after the J point in the inferior leads. During an
      emergency, 12-lead ECG showed that spontaneous onset of VF was preceded by left
      bundle branch block and superior axis-type ventricular extrasystoles. The present
      case provides additional information on the site of origin of VF in patients with
      Brugada syndrome.

PMID- 15851274
TI  - Unusual variant of atrioventricular nodal reentrant tachycardia.
AB  - Electrophysiologic study in a patient with supraventricular tachycardia revealed
      an unusual activation pattern in the coronary sinus (CS) electrodes. Pacing
      maneuvers confirmed the tachycardia was a slow-slow AV nodal reentrant
      tachycardia with double potentials in the distal CS electrodes due to an earlier
      left atrial signal (50 ms) and later CS musculature activation. The left-sided AV
      nodal inputs were successfully ablated from within the CS.

PMID- 15851275
TI  - Strategies for stroke prevention in atrial fibrillation.

PMID- 15851276
TI  - Wide complex tachycardia: what is the mechanism?

PMID- 15851277
TI  - Loss of biventricular pacing: what is the cause?

PMID- 15851278
TI  - Temporary biventricular pacing in a patient with subacute myocardial infarction,
      cardiogenic shock, and third-degree atrioventricular block.

PMID- 15851280
TI  - State of the journal 2005.

PMID- 15851281
TI  - One conversion of ventricular fibrillation is adequate for implantable
      cardioverter-defibrillator implant: an analysis from the Low Energy Safety Study
      (LESS).
AB  - OBJECTIVES: The purpose of this study was to analyze defibrillation conversion
      data from the Low Energy Safety Study (LESS) to determine how implant criteria
      that use fewer inductions of ventricular fibrillation (VF) correlate with outcome
      and, in particular, to assess the reliability of using a single VF induction and
      test shock at 14 J. BACKGROUND: A safety margin of 10 J has become standard for
      implantation of an implantable cardioverter-defibrillator (ICD), but the
      specifics and rigor of the implant test sequence are not standardized. METHODS:
      In LESS, 611 ICD recipients completed a rigorous VF induction test scheme that
      began at 14 J and continued until the energy that succeeded three times without a
      failure was determined (DFT++). The data were analyzed to determine how well the
      outcome of the first 14-J shock and various other combinations of first and/or
      second shocks predicted a rigorous gold standard of DFT++ < or =21 J (i.e., three
      successes at < or =21 J). RESULTS: The positive predictive accuracy for the 91%
      of patients in whom the first 14-J shock succeeded was virtually identical to the
      positive predictive accuracy for the commonly used criteria of two successes at <
      or =17 J (99.1% vs 99.0%, P = .69), and slightly higher than the positive
      predictive accuracy for two successes at < or =21 J (98.8%, P = .51). A single
      success at 17 J or 21 J had a somewhat lower positive predictive accuracy of
      98.2% (P = .17). Eliminating VF induction testing would have resulted in a
      significantly lower positive predictive accuracy of 97.1% (P = .01). CONCLUSIONS:
      A single conversion success at 14 J on the first VF induction provides similar
      positive predictive accuracy as two successes at 17 J or 21 J. Using this
      criterion, 91% of patients meet implant criteria with a single induction of
      ventricular fibrillation.

PMID- 15851282
TI  - Defibrillation threshold testing: is one shock enough?

PMID- 15851284
TI  - Asymptomatic atrial fibrillation and pacemaker diagnostics: the unseen presence.

PMID- 15851283
TI  - Relationship between atrial tachyarrhythmias and symptoms.
AB  - OBJECTIVES: The purpose of this study was to correlate patient-reported symptoms
      of atrial fibrillation with the underlying rhythm. BACKGROUND: The reliability of
      patient-reported symptoms as a marker of atrial fibrillation recurrence has not
      been well studied. METHODS: This prospective multicenter trial correlated the
      recurrence of atrial tachyarrhythmias with symptoms in patients with a history of
      atrial fibrillation and a standard indication for permanent pacing. Pacemaker
      detected atrial tachyarrhythmia events were correlated with symptoms. Patients
      logged symptomatic events into the device's memory via an external manual
      activator. Patients were followed for 12 months and were contacted weekly to
      ensure compliance with activator usage. Episodes were classified as symptomatic
      atrial tachyarrhythmia, asymptomatic atrial tachyarrhythmia, or symptomatic
      nonatrial tachyarrhythmia depending on concordance between patient symptoms and
      the rhythm. RESULTS: Forty-eight patients underwent implantation of a DDDRP
      pacemaker and were followed for 12 +/- 2 months. A median of 25.0 (4.0-55.8)
      symptomatic events attributed to atrial fibrillation. A median of 1.0 (0.0-10.0)
      symptomatic atrial tachyarrhythmia episodes were documented during follow-up.
      Symptoms related to atrial fibrillation were reported in 6% of atrial
      tachyarrhythmia episodes identified by the pacemaker. The probability that
      symptoms were associated with an atrial tachyarrhythmia (positive predictive
      value) was 17%. The ventricular rate between symptomatic and asymptomatic atrial
      tachyarrhythmia events was not significantly different. CONCLUSIONS: Among
      patients with symptomatic bradycardia and a history of atrial fibrillation,
      symptoms of atrial fibrillation often were not associated with documented atrial
      tachyarrhythmias, and more than 90% of atrial tachyarrhythmias were clinically
      silent.

PMID- 15851285
TI  - Genetic susceptibility to acquired long QT syndrome: pharmacologic challenge in
      first-degree relatives.
AB  - OBJECTIVES: The purpose of this study was to test for a genetic component to risk
      for acquired long QT syndrome (LQTS). BACKGROUND: Many drugs prolong the QT
      interval, and some patients develop excessive QT prolongation and occasionally
      torsades de pointes-the acquired LQTS. Similarities between the acquired and
      congenital forms of the long QT syndrome suggest genetic factors modulate
      susceptibility. METHODS: Intravenous quinidine was administered to 14 relatives
      of patients who safely tolerated chronic therapy with a QT-prolonging drug
      (control relatives) and 12 relatives of patients who developed acquired LQTS, and
      ECG intervals between groups were compared. RESULTS: Baseline QT and heart-rate
      corrected QT (QTc) were similar (QT/QTc: 394 +/- 28/410 +/- 20 ms vs 395 +/-
      24/418 +/- 20 ms; control vs acquired LQTS) and prolonged equally in the two
      groups. The interval from the peak to the end of the T wave, an index of
      transmural dispersion of repolarization, prolonged significantly with quinidine
      in acquired LQTS relatives (63 +/- 17 to 83 +/- 18 ms, P = .017) but not in
      control relatives (66 +/- 19 to 71 +/- 18 ms, P = 0.648). In addition, the
      baseline peak to end of the T wave as a fraction of the QT interval was similar
      in both groups but was longer in acquired LQTS relatives after quinidine (16.3 +/
      3.5% and 19.5 +/- 3.9% in control and acquired LQTS relatives, respectively, P =
      .042). CONCLUSIONS: First-degree relatives of patients with acquired long QT
      syndrome have greater drug-induced prolongation of terminal repolarization
      compared to control relatives, supporting a genetic predisposition to acquired
      long QT syndrome.

PMID- 15851286
TI  - Epinephrine-induced T-wave notching in congenital long QT syndrome.
AB  - OBJECTIVES: The purpose of this study was to characterize the effect of
      epinephrine on T-wave morphology in patients with congenital long QT syndrome
      (LQTS). BACKGROUND: QT prolongation is a paradoxical, LQT1-specific response to
      low-dose epinephrine infusion. At rest, notched T waves are more common in LQT2.
      METHODS: Thirty subjects with LQT1, 28 with LQT2, and 32 controls were studied
      using epinephrine provocation. Twelve-lead ECG was recorded continuously, and QT,
      QTc, and heart rate were obtained during each stage. Blinded to phenotype and
      genotype, T-wave morphology was classified as normal, biphasic, G1 (notch at or
      below the apex), or G2 (distinct protuberance above the apex). RESULTS: At
      baseline, 97% LQT1, 71% LQT2, and 94% control had normal T-wave profiles. During
      epinephrine infusion, G1- and G2-T waves were more common in LQT2 than in LQT1
      (75% vs 26%, P = .009). However, epinephrine-induced G1-T waves were present in
      34% of control. Epinephrine-precipitated biphasic T waves were observed similarly
      in all groups: LQT1 (6/30), LQT2 (3/28), and control (4/32). During low-dose
      epinephrine infusion (< or =0.05 microg/kg/min), G1-T waves occurred more
      frequently in LQT2 (LQT1: 25% vs 3%; control 9%, P = .02). Low-dose epinephrine
      induced G2-T waves were detected exclusively in LQT2 (18%). Low-dose epinephrine
      elicited G1/G2-T waves in 8 of 15 LQT2 patients with a nondiagnostic baseline
      QTc. CONCLUSIONS: Biphasic and G1-T waves are nonspecific responses to high-dose
      epinephrine. Changes in T-wave morphology during low-dose epinephrine (<0.05
      microg/kg/min) may yield diagnostic information. G2-notched T waves elicited
      during low-dose epinephrine may unmask some patients with concealed LQT2.

PMID- 15851287
TI  - Provocation testing in inherited arrhythmia disorders: can we be more specific?

PMID- 15851288
TI  - Response of beat-by-beat QT variability to sympathetic stimulation in the LQT1
      form of congenital long QT syndrome.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that the
      lability of beat-by-beat QT variability is prominent during sympathetic
      stimulation in LQT1 patients. We analyzed beat-by-beat QT variability using a
      newly developed program and applied cross-correlation methods in LQT1 patients
      before and after epinephrine infusion. BACKGROUND: Studies suggest that cardiac
      events associated with sympathetic stimulation are more common in the LQT1 form
      than the LQT2 and LQT3 forms of congenital long QT syndrome (LQTS). Although beat
      by-beat alternation of T-wave morphology is observed in LQTS, its objective
      estimation is difficult because of complicated T-wave morphology. METHODS: Twelve
      lead ECG was recorded under baseline conditions and during epinephrine infusion
      (0.1 mug/kg/min) in 14 LQT1 and five control patients. We measured beat-by-beat
      QT interval by a cross-correlation technique. Mean of successive changes in RR
      (DeltaRR), QT (DeltaQT), standard deviation of DeltaRR (SD-DeltaRR), DeltaQT (SD
      DeltaQT), and QTI (QT/ RR) before and after epinephrine were compared between the
      two groups. RESULTS: No significant differences in any parameters were observed
      between the two groups under baseline conditions. DeltaQT, SD-DeltaQT, and QTI
      were increased in LQT1 but not in control patients during epinephrine (LQT1:
      DeltaQT 2.3-4.2 ms, SD-DeltaQT 2.2-4.1, QTI 0.10-0.22, P < .005 vs baseline;
      CONTROL: DeltaQT 2.5-2.4 ms, SD-DeltaQT 1.9-2.1, QTI 0.08-0.09: P = NS vs
      baseline). CONCLUSIONS: Beat-by-beat QT variability analyzed by the cross
      correlation method was greater in LQT1 patients during epinephrine infusion,
      suggesting sympathetic stimulation accentuates beat-by-beat alternation of
      repolarization in LQT1 patients.

PMID- 15851289
TI  - Long-term changes in sequence of atrial activation and refractory periods: no
      evidence for "atrial memory".
AB  - OBJECTIVES: The purpose of this study was to test whether the spatial
      distribution of the atrial refractory period (AERP) and the vulnerability to
      atrial fibrillation (AF) are altered by long-term changes in the sequence of
      atrial activation. BACKGROUND: The spatial distribution of the AERP plays an
      important role in AF. Changes in the activation sequence have been postulated to
      modulate atrial repolarization ("atrial memory"). METHODS: Six goats were
      chronically instrumented with epicardial atrial electrodes to determine
      activation time and AERP at 11 different areas of the right (RA) and left (LA)
      atrium and the Bachmann bundle. Activation time and AERP were measured during
      sinus rhythm and during prolonged RA and LA pacing (1 week RA pacing, 2 weeks LA
      pacing, 1 week RA pacing; 150 bpm). Inducibility of AF was determined by the
      number of atrial sites where single premature stimuli induced AF paroxysms >1
      second. RESULTS: During sinus rhythm (106 +/- 4 bpm), AERP was longest at the
      Bachmann bundle and shortest at the LA free wall (185 +/- 6 ms and 141 +/- 5 ms,
      P < .001). In five of six goats, an inverse correlation between local activation
      time and AERP was found during sinus rhythm (r = -0.53 +/- 0.05; P < .05). The
      increase in atrial rate during RA and LA pacing caused an overall shortening of
      AERP from 167 +/- 6 ms to 140 +/- 6 ms (P < .001). However, a switch between long
      term RA and LA pacing did not significantly change AERP at any of the 11 atrial
      regions and had no significant effect on AF inducibility. CONCLUSIONS: During
      sinus rhythm, an inverse relationship exists between the sequence of atrial
      activation and the local refractory period. However, long-term changes in the
      sequence of atrial activation do not alter the spatial distribution of AERP or
      the inducibility of AF.

PMID- 15851290
TI  - In vivo validation of the coincidence of the peak and end of the T wave with full
      repolarization of the epicardium and endocardium in swine.
AB  - OBJECTIVES/BACKGROUND: Previous in vitro studies have suggested full
      repolarization of the epicardium coincides with the peak of the T wave (T(peak))
      and that of the M cells coincides with the end of the T wave (T(end)). However,
      in vivo validation of the theory is lacking. METHODS: Monophasic action
      potentials (MAPs) were recorded using the CARTO mapping system from 51 +/- 10
      epicardial sites and 64 +/- 9 endocardial sites of the left ventricle in 10 pigs
      and from 41 +/- 4 epicardial sites and 53 +/- 2 endocardial sites of the right
      ventricle in two of the 10 pigs. End of repolarization (EOR) times over the
      epicardium (EOR(epi)), endocardium (EOR(endo)), and over both (EOR(total)) were
      obtained. QT(peak) and QT(end) intervals were measured from simultaneously
      recorded 12-lead ECG. RESULTS: Minimal and maximal EOR(total) were observed in
      the left ventricle in all pigs. Minimal EOR(total) was on the epicardium in five
      pigs, and maximal EOR(total) was on the endocardium in nine pigs. Minimal, mean,
      and maximal QT(peak) intervals all were significantly smaller than maximal
      EOR(epi) (322 +/- 23 ms, P <.01). No significant difference was found between
      maximal QT(end) interval (338 +/- 30 ms) and maximal EOR(endo) (339 +/- 24 ms,
      difference = 1 +/- 19 ms, P =.92), between maximal QT(end) interval and maximal
      EOR(total) (341 +/- 24 ms, difference = 2 +/- 18 ms, P =.69), or between minimal
      QT(peak) interval (283 +/- 28 ms) and minimal EOR(total) (282 +/- 20 ms,
      difference = 0 +/- 15 ms, P =.95). CONCLUSIONS: In in vivo pig models, T(peak)
      does not coincide with full repolarization of the epicardium but coincides well
      with the earliest EOR, whereas the T(end) corresponds with the latest EOR. These
      findings suggest that not only the transmural gradients but also the apicobasal
      repolarization gradients contribute to genesis of the T wave.

PMID- 15851291
TI  - T wave and dispersion of repolarization.

PMID- 15851293
TI  - Regional discrepancies in ionic currents and arrhythmia susceptibility: clinical
      relevance.

PMID- 15851292
TI  - Regional dispersion of L-type calcium current in ventricular myocytes of German
      shepherd dogs with lethal cardiac arrhythmias.
AB  - OBJECTIVES: The purpose of this study was to determine if regional differences in
      L-type Ca(2+) current (I(Ca,L)) are altered in a German shepherd model of sudden
      death. BACKGROUND: German shepherd dogs with inherited sudden cardiac death have
      reduced sympathetic innervation in the anteroseptal left ventricle that may
      contribute to arrhythmias in afflicted animals compared to control unafflicted
      animals. Differences in a number of repolarizing K(+) currents have been
      identified in this model, but I(Ca,L) has not been studied. METHODS: We measured
      action potentials in intact tissue and I(Ca,L) in isolated myocytes from
      anteroseptal and anterobasal left ventricle. RESULTS: Action potential plateau
      level and I(Ca,L) density were significantly lower in unafflicted anteroseptal
      than in afflicted anteroseptal, afflicted anterobasal, or unafflicted
      anterobasal. Isoproterenol increased I(Ca,L) density more in the unafflicted
      anteroseptal group than in the other groups. CONCLUSIONS: Differences in I(Ca,L)
      between afflicted and control animals, combined with our earlier finding of
      regional reductions in I(Kr), provide a likely substrate for the occurrence of
      pause-dependent arrhythmias in afflicted animals and for the T-wave abnormalities
      characterizing them.

PMID- 15851294
TI  - Radiofrequency ablation of Mahaim pathway during atrial fibrillation.

PMID- 15851295
TI  - Transient left recurrent laryngeal nerve palsy following catheter ablation of
      atrial fibrillation.

PMID- 15851296
TI  - Recurrent paroxysmal atrioventricular block triggered paradoxically by a
      pacemaker.

PMID- 15851297
TI  - Atrioventricular conduction in mammalian species: hemodynamic and electrical
      scaling.
AB  - OBJECTIVES: The purpose of this study was to investigate scaling of the duration
      of late diastolic left ventricular (LV) filling in relation to AV conduction time
      (delay) (PR interval on the ECG) in mammals. BACKGROUND: From mouse to whale, AV
      delay increases 10-fold, whereas body mass increases one million-fold. The
      apparent "mismatch" results from scaling of AV delay versus body and heart mass.
      METHODS: We measured (1) mitral orifice diameter in 138 postmortem hearts of 48
      mammalian species weighing between 17 g and 250 kg and (2) transmitral diastolic
      flow using magnetic resonance imaging (MRI) recordings of 10 healthy human
      individuals. (3) We visually inspected early and late diastolic LV filling. (4)
      We developed two physical models to explain scaling of late diastolic LV filling
      time. RESULTS: (1) Diameter of the mitral orifice proportionally relates to heart
      length (third root of heart mass). (2) Atrial contraction starts at a fixed
      instant (+/- 80%) of the (normalized) cardiac cycle and contributes 31% +/- 5% to
      LV filling. (3) MRI shows that during diastole, the left atrium (LA) and LV form
      a single space. (4) The physical models relate the duration of late diastolic LV
      filling directly to heart length, the third root of heart mass. CONCLUSIONS: (1)
      Late diastolic (LV) filling time scales with heart length (third root of heart
      mass). (2) No "mismatch" exists between AV delay and heart size. (3) Knowledge of
      the actual starting time of atrial contraction may contribute to better treatment
      of patients with heart failure. (4) The findings suggest that in evolution of
      mammalian species, hemodynamics commands electrical behavior of the heart.

PMID- 15851298
TI  - The Sisyphean task of atrioventricular nodal scaling: is the stone at the top of
      the mountain?

PMID- 15851299
TI  - Pacing the right ventricle: to pace or not to pace?

PMID- 15851300
TI  - Paroxysmal supraventricular tachycardia with atrioventricular block: what is the
      mechanism?

PMID- 15851301
TI  - Atrial pacing above the sensor rate: what is the cause?

PMID- 15851302
TI  - Transseptal catheterization.

PMID- 15851303
TI  - Migration of an Accufix atrial lead retention wire to the anterior mediastinum.

PMID- 15851304
TI  - Clinical considerations for the allied professional: programming issues in
      cardiac resynchronization therapy.

PMID- 15851305
TI  - ECG during sinus rhythm in patients with atriofascicular Mahaim fibers:
      importance of an rS pattern in lead III.

PMID- 15851306
TI  - More on Philip Coumel.

PMID- 15851308
TI  - Does flecainide regain its antiarrhythmic activity after electrical cardioversion
      of persistent atrial fibrillation?
AB  - OBJECTIVES: The purpose of this study was to evaluate the hypothesis that
      presumed reversion of electrical remodeling after cardioversion of atrial
      fibrillation (AF) restores the efficacy of flecainide. BACKGROUND: Flecainide
      loses its efficacy to cardiovert when AF has been present for more than 24 hours.
      Most probably, the loss is caused by atrial electrical remodeling. Studies
      suggest electrical remodeling is completely reversible within 4 days after
      restoration of sinus rhythm (SR). METHODS: One hundred eighty-one patients with
      persistent AF (median duration 3 months) were included in this prospective study.
      After failure of pharmacologic cardioversion by flecainide 2 mg/kg IV (maximum
      150 mg in 10 minutes) and subsequent successful electrical cardioversion, we
      performed intense transtelephonic rhythm monitoring three times daily for 1
      month. In case of AF recurrence, a second cardioversion by flecainide was
      attempted as soon as possible. RESULTS: AF recurred in 123 patients (68%).
      Successful cardioversion by flecainide occurred only when SR had been maintained
      for more than 4 days (7/51 patients [14%]). Failure to cardiovert was associated
      with a prolonged duration of the recurrent AF episode and concurrent digoxin use.
      Multivariate logistic regression confirmed that successful cardioversion was
      determined by digoxin use (odds ratio [OR] 0.093, P = .047) and by the
      interaction between the duration of SR and the (inverse) duration of recurrent AF
      (OR 6.499, P < .001). When flecainide was administered within 10 hours after AF
      onset and the duration of SR was greater than 4 days, the success rate was 58%.
      CONCLUSIONS: Flecainide recovers its antiarrhythmic action after cardioversion of
      AF. However, successful pharmacologic cardioversion occurs only after SR has
      lasted at least 4 days and is expected only for recurrences having duration of a
      few hours. Immediate pharmacologic cardioversion of AF recurrence may be a
      worthwhile strategy for management of persistent AF.

PMID- 15851309
TI  - With pharmacologic conversion of atrial fibrillation, is timing everything?

PMID- 15851310
TI  - T-wave alternans phase following ventricular extrasystoles predicts arrhythmia
      free survival.
AB  - OBJECTIVE: The purpose of this study was to assess the value of T-wave alternans
      (TWA) following ventricular extrasystoles in predicting arrhythmia-free survival.
      BACKGROUND: Stratifying risk for sudden death in patients with coronary disease
      and moderate left ventricular (LV) dysfunction remains a challenge. We
      hypothesized that, in such patients, a discontinuity in beat-to-beat T-wave
      alternation (TWA phase reversal) following single ventricular extrasystoles
      reflects transiently exaggerated repolarization dispersion, and predicts
      spontaneous ventricular arrhythmias. METHODS: We studied 59 patients with
      ischemic LV dysfunction (mean LV ejection fraction 38.7 +/- 5.3%) and
      nonsustained ventricular tachycardia undergoing programmed stimulation. TWA was
      computed spectrally from the ECG during ventricular pacing, and TWA phase
      reversal was reflected by a discontinuity in T-wave oscillation after single
      ventricular extrasystoles. RESULTS: Patients induced into ventricular arrhythmias
      (n = 36) had greater TWA magnitude (V(alt): 6.60 +/- 6.46 microV vs 2.61 +/- 1.97
      microV; P = .001) and more frequent TWA phase reversal (62.1% vs 44.4%; P = .02)
      than those who were not (n = 23). During a mean follow-up of 36 +/- 12 months,
      positive TWA (V(alt) > or =1.9 microV) and TWA phase reversal both (P < .05)
      predicted events (all-cause mortality, ventricular tachycardia, ventricular
      fibrillation). Univariate predictors of arrhythmia-free survival were TWA phase
      reversal (P < .005), positive TWA (P < .05), age (P = .008), and LV mass index (P
      = .043). On multivariate analysis, only TWA phase reversal and age predicted
      events; if TWA phase was excluded, only positive TWA and age predicted events.
      CONCLUSION: Phase reversal in TWA following ventricular extrasystoles predicts
      spontaneous ventricular arrhythmias and all-cause mortality in patients with
      moderate ischemic LV dysfunction and was a better predictor than positive TWA or
      programmed ventricular stimulation.

PMID- 15851311
TI  - Should T-wave alternans testing be used to risk stratify candidates for
      prophylactic implantable cardioverter-defibrillator therapy?

PMID- 15851312
TI  - Heart failure hospitalization is more common in pacemaker patients with sinus
      node dysfunction and a prolonged paced QRS duration.
AB  - OBJECTIVES: The purpose of this study was to determine whether a prolonged paced
      QRS duration increases the risk of cardiac dysfunction. BACKGROUND: Right
      ventricular apical pacing mimics left bundle branch block, results in a prolonged
      QRS duration of variable duration, and causes ventricular desynchronization.
      METHODS: In the Mode Selection Trial (MOST), QRS duration was measured in
      patients who had at least one paced ventricular complex recorded on 12-lead ECG
      within 3 months of enrollment (early) and after 9 months (late). Clinical
      endpoints including heart failure hospitalization, mortality, and atrial
      fibrillation were analyzed. A total of 1,026 patients were included in the
      analysis. Median age was 75 years (25th, 75th percentiles = 69, 80) and median
      ejection fraction prior to implant was 55% (45, 60). The cumulative percent
      ventricular pacing (DDDR and VVIR) was 81% over a median follow-up of 33 months.
      During period, 123 patients had heart failure hospitalization, 197 died, and 261
      patients had atrial fibrillation. RESULTS: Cox proportional hazards models
      demonstrated that paced QRS duration was a strong predictor of heart failure
      hospitalization (hazard ratio 1.15; 95% confidence interval 1.07,1.23) for each
      10-ms increase in paced QRS duration (P = .001). The increased risk was
      unaffected by adjustment for other known predictors of heart failure
      hospitalization in the study. Paced QRS duration was not significant for
      mortality (P = .41) or atrial fibrillation (P = .20) when baseline QRS duration
      and other predictors were included. CONCLUSIONS: Paced QRS duration is a
      significant, independent predictor of heart failure hospitalization in patients
      with sinus node dysfunction. A very long paced QRS duration is associated with
      increased heart failure hospitalization.

PMID- 15851313
TI  - Iatrogenic ventricular dyssynchrony: a preventable cause of heart failure with
      right ventricular pacing?

PMID- 15851315
TI  - Are all sodium channel blockers created equal? Clinical-basic correlations based
      on observations in Brugada syndrome.

PMID- 15851314
TI  - Intravenous drug challenge using flecainide and ajmaline in patients with Brugada
      syndrome.
AB  - OBJECTIVES: The purpose of this study was to compare the effect of intravenous
      flecainide and ajmaline with respect to their ability to induce or accentuate the
      typical ECG pattern of Brugada syndrome. BACKGROUND: Brugada syndrome is
      associated with a high incidence of sudden cardiac death. The typical ECG pattern
      of ST-segment elevation in the right precordial leads often is concealed, but it
      can be unmasked with sodium channel blockers such as flecainide and ajmaline.
      Little is known about the relative effectiveness of these provocative agents in
      unmasking Brugada syndrome. METHODS: Intravenous pharmacologic challenge with
      flecainide and ajmaline was performed. Whole-cell patch clamp techniques were
      used to assess the relative potency of ajmaline and flecainide to inhibit the
      transient outward current (I(to)). RESULTS: A coved-type ST-segment elevation in
      the right precordial leads was induced or enhanced in 22 of 22 patients following
      ajmaline administration. Among the 22 patients, only 15 patients showed positive
      response to flecainide, resulting in a positive concordance of 68%. Both drugs
      produced equivalent changes in QRS and PQ intervals, suggesting similar effects
      on sodium channel current. Whole-cell patch clamp experiments revealed a
      reduction of the total charge provided by I(to) with an IC(50) of 216 and 15.2
      microM for ajmaline and flecainide, respectively. CONCLUSIONS: Our data
      demonstrate disparate response of Brugada patients to flecainide and ajmaline,
      with a failure of flecainide in 7 of 22 cases (32%). Greater inhibition of I(to)
      by flecainide may render it less effective. These observations have important
      implication for identification of patients at risk for sudden death.

PMID- 15851316
TI  - Correlation of atrial electrocardiographic amplitude with radiofrequency energy
      required to ablate cavotricuspid isthmus-dependent atrial flutter.
AB  - OBJECTIVES: The purpose of this study was to evaluate a possible correlation
      between atrial ECG amplitude in common atrial flutter (AFL) and radiofrequency
      (RF) energy required to achieve cavotricuspid isthmus block. BACKGROUND: The
      amount of RF delivery required for ablation of typical AFL is variable. This
      variation has been attributed to the cavotricuspid isthmus anatomy. Atrial ECG
      amplitude can be a marker of atrial anatomic variations and therefore may
      correlate with RF duration required to achieve cavotricuspid isthmus block.
      METHODS: Seventy consecutive patients were prospectively studied. Ablation of the
      cavotricuspid isthmus was performed by creating a line of block between the
      inferior tricuspid annulus and the inferior caval vein using 8-mm-tip electrode
      catheters. If more than 20 minutes of RF time was required to achieve conduction
      block, the catheter was changed to an irrigated-tip catheter. Atrial ECG
      amplitude was assessed in leads II, III, aVF, and aVL. RESULTS: A total of 14 +/-
      11 minutes of RF energy was delivered to achieve block in all patients; 12
      patients (8%) required more than 20 minutes. Atrial ECG amplitude showed highly
      significant correlations with cumulative RF energy (F and P waves in lead II: r =
      0.703 and r = 0.737, P < .001). P-wave amplitude <0.2 mV and/or flutter wave
      amplitude <0.35 mV in lead II have a high negative predictive value to predict
      <20 min RF delivery (96% and 89% respectively). CONCLUSIONS: A significant
      correlation exists between atrial ECG amplitude and amount of RF required to
      ablate typical AFL. Atrial ECG amplitude may be a surrogate marker of
      characteristics of isthmus anatomy. These findings may influence the choice of
      catheter used for cavotricuspid isthmus ablation.

PMID- 15851317
TI  - Cost-effectiveness of physiologic pacing: results of the Canadian Health Economic
      Assessment of Physiologic Pacing.
AB  - OBJECTIVES: The purpose of this study was to determine the cost-effectiveness of
      physiologic pacemakers. BACKGROUND: The Canadian Trial of Physiologic Pacing
      (CTOPP) was a large randomized trial that evaluated the efficacy of physiologic
      pacing compared with ventricular pacing. CTOPP also included a prospective cost
      effectiveness substudy. METHODS: Resource usage and costs were collected from a
      subset of 472 patients (of 1,094) who received a physiologic pacemaker and 586
      (of 1,474) who received a ventricular pacemaker. Costs included initial pacemaker
      implantation and all health care follow-up costs over a follow-up of 5.2 years.
      Costs are reported in 2004 Canadian dollars (1 Canadian dollar = 0.76 US
      dollars), with adjustments for censoring. Incremental cost-effectiveness was
      estimated as the ratio of the difference (treatment-control) in mean cost to the
      difference in life expectancy (mean survival), with costs and effects discounted
      at 3% per year. RESULTS: Over a mean follow-up of 3.1 years, physiologic pacing
      was associated with a gain of 0.01 life-years. This benefit increases to 0.25
      life-years in the subgroup of patients with an intrinsic (unpaced) heart rate <
      or =60 bpm. Physiologic pacing was more expensive than ventricular (16,833
      Canadian dollars vs 13,857 US dollars), largely because of the increased cost of
      dual-chamber devices. Among all substudy patients, the incremental cost
      effectiveness of physiologic pacing is 297,600 Canadian dollars per life-year
      gained; however, this value falls to 16,343 Canadian dollars in patients with an
      intrinsic heart rate >60. CONCLUSIONS: In the short term, a strategy of routine
      implantation of physiologic pacemakers is not cost-effective by currently
      accepted standards. The selective use of these devices in patients likely to be
      pacemaker dependent appears to be cost-effective. Further studies with longer
      follow-up and which consider the benefit of reducing nonfatal cardiac events
      would be valuable.

PMID- 15851318
TI  - Can an expensive therapy save lives if the disease is not life threatening?

PMID- 15851319
TI  - QT interval is a heritable quantitative trait with evidence of linkage to
      chromosome 3 in a genome-wide linkage analysis: The Framingham Heart Study.
AB  - OBJECTIVES: To identify genomic regions linked to QT interval duration in an
      unselected population. BACKGROUND: QT interval prolongation is associated with
      increased risk of sudden cardiac death and coronary heart disease and may result
      from acquired conditions or inherited ion channel defects. The influence of
      genetic variants on QT interval length in apparently healthy individuals is
      uncertain. METHODS: We studied subjects from the Framingham Heart Study in whom
      12-lead ECGs were available from regular clinic examinations. QT, QT-peak, and RR
      intervals were measured using digital calipers. A 10-centiMorgan (cM) density
      genome-wide scan was performed in a subset of the largest families having at
      least two members with ECG phenotypes (326 families). Variance components methods
      (Genehunter) were used. RESULTS: Evidence was observed for significant
      heritability of the QT interval (h(2) 0.35; 95% CI, 0.29-0.41), QT-peak interval
      (h(2) 0.37; 95% CI, 0.29-0.45), and calculated JT interval (h(2) 0.25; 95% CI,
      0.19-0.31). In the genome-wide linkage analysis, we found suggestive evidence for
      linkage of the QT interval 19 to 48 cM from the tip of the short arm of
      chromosome 3 (maximum two-point LOD score 3.00, maximum multipoint LOD score
      2.71). After fine-mapping with seven microsatellite markers, the peak multipoint
      LOD score rose to 2.84 at 24.4 cM. The region of linkage contains potassium and
      sodium channel genes, including the SCN5A gene, which has been implicated in one
      form of the long QT syndrome and in the Brugada syndrome. CONCLUSIONS: QT and
      related ECG intervals are heritable traits in a large unselected population. We
      provide suggestive evidence for a quantitative trait locus on chromosome 3
      influencing QT interval duration. Further studies are warranted to identify genes
      that influence QT interval variation and to determine the role of heritable
      factors in life-threatening QT prolongation.

PMID- 15851320
TI  - Double SCN5A mutation underlying asymptomatic Brugada syndrome.
AB  - OBJECTIVES: The purpose of this study was to identify risk markers in patients
      with Brugada syndrome. BACKGROUND: Patients with Brugada syndrome who experience
      syncope or aborted sudden death are at high risk for recurrent lethal
      arrhythmias. The prognosis and therapeutic approaches in asymptomatic individuals
      with a Brugada-type ECG (asymptomatic Brugada syndrome) are controversial.
      METHODS: We genetically screened 30 asymptomatic probands (29 men and 1 woman;
      mean age 47.1 years) exhibiting a spontaneous Brugada-type ECG. Family members of
      patients with Brugada syndrome were excluded from the study. RESULTS: Twenty-nine
      of 30 patients (96.7%) remained symptom-free for at least 3 years. One patient
      (case 1) with a family history of sudden death died suddenly during sleep.
      Ventricular fibrillation was induced by programmed electrical stimulation in 14
      of 18 subjects (78%), but none of these 18 subjects developed spontaneous
      ventricular arrhythmias. Genetic screening failed to identify SCN5A mutations in
      most cases but demonstrated a novel double missense mutation (K1527R and A1569P)
      located on the same allele in another asymptomatic subject (case 2).
      Heterologously expressed mutant Na channels exhibited a negative shift of steady
      state inactivation (9.2 mV) and enhanced slow inactivation, suggesting this
      individual harbors a subclinical channel dysfunction compatible with symptomatic
      Brugada syndrome. CONCLUSIONS: Asymptomatic individuals with a Brugada-type ECG
      generally have a better prognosis than their symptomatic counterparts, but a
      subgroup of these individuals may have a poor prognosis. Severe Na channel
      dysfunction as a result of SCN5A mutations may not be sufficient to cause
      symptoms or arrhythmias in patients with Brugada syndrome, suggesting unknown
      factors or modifier genes influence arrhythmogenesis.

PMID- 15851322
TI  - Early rate control in complete atrioventricular block is warranted to prevent
      electrical remodeling: No role for ventricular activation?

PMID- 15851321
TI  - Ventricular rate determines early bradycardic electrical remodeling.
AB  - OBJECTIVES: The purpose of this study was to isolate chronic ventricular rate as
      the primary determinant of early bradycardic ventricular electrical remodeling.
      BACKGROUND: Ventricular repolarization delay predisposing to potentially lethal
      tachydysrhythmias occurs during chronic bradycardia. Prolonged QT intervals and
      torsades de pointes are associated with down-regulated ventricular myocyte
      delayed rectifier potassium (K(+)) currents. METHODS: Transcatheter AV node
      ablation in rabbits was followed by chronic right ventricular pacing at either
      140 bpm (n = 16) or the near-physiologic rate of 280 bpm (n = 9). ECG QT
      intervals were assessed in vivo at days 0 and 8 of paced AV block. Repolarizing
      currents in isolated left and right ventricular myocytes were assessed using
      whole-cell patch clamp technique. RESULTS: Bradycardic rabbits had increased
      steady-state QT intervals (230 +/- 6 ms vs 206 +/- 7 ms [mean +/- SE], day 8 vs
      day 0; P < .001). Biventricular myocyte expression of the delayed rectifier K(+)
      currents I(Kr) and I(Ks) was down-regulated in bradycardic rabbits, with no
      change in the transient outward current I(to) or inwardly rectifying current
      I(K1). None of these changes were observed in rabbits paced at 280 bpm. Pause
      dependent torsades de pointes was documented in one bradycardic animal on day 8.
      No heart failure or ventricular hypertrophy was apparent. CONCLUSIONS:
      Bradycardic ventricular electrical remodeling proceeds independently of
      structural remodeling, heart failure, or AV synchrony and is prevented by
      maintenance of near-physiologic ventricular rate.

PMID- 15851323
TI  - Congenital long QT syndrome aggravated by salt-wasting nephropathy.

PMID- 15851324
TI  - Inappropriate therapy and fatal proarrhythmia by an implantable cardioverter
      defibrillator.

PMID- 15851325
TI  - Cross-talk inhibition and asystole resulting from postshock high-output pacing: a
      new form of implantable cardioverter-defibrillator proarrhythmia.

PMID- 15851326
TI  - Congenital junctional ectopic tachycardia and congenital complete
      atrioventricular block: a shared etiology?

PMID- 15851327
TI  - The inward rectifier current (IK1) controls cardiac excitability and is involved
      in arrhythmogenesis.
AB  - The cardiac inwardly rectifying potassium current (I(K1)) stabilizes the resting
      membrane potential and is responsible for shaping the initial depolarization and
      final repolarization of the action potential. The inwardly rectifying potassium
      channel (Kir2.x) subfamily members primarily mediate cardiac I(K1), but other
      inward rectifiers, including the acetylcholine-sensitive (Kir3.x) and ATP
      sensitive (Kir6.x) inward rectifiers, also may modulate cardiac excitability.
      Studies suggest I(K1) plays a role in ventricular arrhythmias, highlighted by the
      recently described Andersen's syndrome and studies in the guinea pig heart model
      of ventricular fibrillation. This article describes the salient properties of
      cardiac I(K1) and discusses the role of this current in the cardiac action
      potential and in underlying regional differences in cardiac excitability. The
      mechanism of channel block, assembly, and structure are reviewed. The article
      discusses the role of I(K1) in ventricular fibrillation and speculates on
      modulation of I(K1) as a preventative antiarrhythmic mechanism.

PMID- 15851328
TI  - Right bundle branch block and second-degree atrioventricular block: what is the
      mechanism?

PMID- 15851329
TI  - Determining inferior vena cava-tricuspid isthmus block after typical atrial
      flutter ablation.

PMID- 15851330
TI  - Atrial tachycardia originating from the coronary sinus ostium dissociated with
      fibrillatory activity inside persistent left superior vena cava.

PMID- 15851332
TI  - Catheter ablation of supraventricular tachycardias paper.

PMID- 15851333
TI  - Noninvasive electrocardiographic imaging (ECGI): comparison to intraoperative
      mapping in patients.
AB  - OBJECTIVES/BACKGROUND: Cardiac arrhythmias are a leading cause of death and
      disability. Electrocardiographic imaging (ECGI) is a noninvasive imaging modality
      that reconstructs potentials, electrograms, and isochrones on the epicardial
      surface from body surface measurements. We previously demonstrated in animal
      experiments through comparison with simultaneously measured epicardial data the
      high accuracy of ECGI in imaging cardiac electrical events. Here, images obtained
      by noninvasive ECGI are compared to invasive direct epicardial mapping in open
      heart surgery patients. METHODS: Three patients were studied during sinus rhythm
      and right ventricular endocardial and epicardial pacing (total of five datasets).
      Body surface potentials were acquired preoperatively or postoperatively using a
      224-electrode vest. Heart-torso geometry was determined preoperatively using
      computed tomography. Intraoperative mapping was performed with two 100-electrode
      epicardial patches. RESULTS: Noninvasive potential maps captured epicardial
      breakthrough sites and reflected general activation and repolarization patterns,
      localized pacing sites to approximately 1 cm and distinguished between epicardial
      and endocardial origin of activation. Noninvasively reconstructed electrogram
      morphologies correlated moderately with their invasive counterparts (cross
      correlation = 0.72 +/- 0.25 [sinus rhythm], 0.67 +/- 0.23 [endocardial pacing],
      0.71 +/- 0.21 [epicardial pacing]). Noninvasive isochrones captured the sites of
      earliest activation, areas of slow conduction, and the general excitation
      pattern. CONCLUSIONS: Despite limitations due to nonsimultaneous acquisition of
      the surgical and noninvasive data under different conditions, the study
      demonstrates that ECGI can capture important features of cardiac electrical
      excitation in humans noninvasively during a single beat. It also shows that
      general excitation patterns and electrogram morphologies are largely preserved in
      open chest conditions.

PMID- 15851334
TI  - Electrocardiographic imaging: A confluence of technologies and research
      communities.

PMID- 15851335
TI  - QT dynamics in risk stratification after myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to compare measures of repolarization
      dynamics (QT dynamics) with other Holter risk predictors, left ventricular
      systolic function, and demographic characteristics to establish whether QT
      dynamics add independent information on risk stratification after myocardial
      infarction (MI). A novel QT dynamics parameter, the QT/RR variability ratio (VR),
      was introduced in this study. BACKGROUND: Abnormal repolarization contributes to
      arrhythmogenesis, and quantification of QT dynamics may have prognostic value
      after MI. METHODS: A 24-hour Holter recording was performed in 481 consecutive MI
      patients. Recordings from 311 patients were included in the analysis. QT/RR slope
      and intercept, mean and standard deviation of all QT, QTc, and RR intervals, and
      VR (defined as the ratio between the standard deviation of all QT intervals and
      the standard deviation of all RR interval) were calculated. Ventricular premature
      beats and ventricular tachycardia were counted. RESULTS: During 3-year follow-up,
      70 deaths from all causes occurred. All parameters except mean of all QT
      intervals and standard deviation of all QTc intervals univariately predicted all
      cause mortality. In multivariate Cox analysis, only VR per 0.1 (hazard ratio
      [HR]: 1.9 [1.5-2.4]), left ventricular ejection fraction per 5% (HR: 1.2 [1.1
      1.3]), ventricular premature beats per 10 beats/hour (HR: 1.03 [1.002-1.06]), and
      age per 10 years (HR: 1.6 [1.3-2.0]) independently predicted all-cause mortality.
      CONCLUSIONS: Measures of QT dynamics univariately predicted total mortality. VR,
      left ventricular ejection fraction, ventricular premature beats, and age made up
      the optimal Cox model for risk stratification after MI. VR seems to be a
      promising risk factor for identifying sudden arrhythmic death.

PMID- 15851336
TI  - Risk stratification in postmyocardial infarction patients: Is there reason to
      hope?

PMID- 15851337
TI  - Implantable cardioverter-defibrillator therapy improves long-term survival in
      patients with unexplained syncope, cardiomyopathy, and a negative
      electrophysiologic study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the long-term outcomes of
      patients with unexplained syncope, ischemic or nonischemic cardiomyopathy, and a
      negative electrophysiologic study (EPS). BACKGROUND: EPS is frequently performed
      to evaluate syncope in patients with left ventricular dysfunction. Limited long
      term data evaluating all-cause mortality in patients with no inducible arrhythmia
      or examining the potential benefits from implantable cardioverter-defibrillator
      (ICD) therapy are available. METHODS: We evaluated 102 consecutive patients with
      unexplained syncope, cardiomyopathy, and a negative EPS from September 1996 to
      December 2000. A blinded matched case-control analysis utilized 51 of these
      patients (19 treated with an ICD and 32 matched controls treated with
      conventional therapy). We compared primary endpoint of death and documented
      cardiac arrest of patients treated with ICD therapy to matched controls. RESULTS:
      Baseline characteristics were similar between groups. There were 14 primary
      events among the study population during a follow-up period of 44.3 +/- 20
      months: 2 in the ICD group and 12 in the conventional therapy group. The hazard
      ratio for the risk of event in the ICD group compared with the conventional
      therapy group was 0.18 (95% confidence interval, 0.04-0.85; P = .04). Other
      comorbid conditions, including age, sex, ischemic etiology of heart failure,
      ejection fraction, and antiarrhythmic use, did not predict outcome. Appropriate
      ICD shocks occurred in 26% of patients at 2 years. CONCLUSIONS: This study
      suggests that empiric ICD therapy improves long-term outcomes in patients with
      unexplained syncope, ischemic or nonischemic cardiomyopathy, and negative EPS.

PMID- 15851338
TI  - "Show-me" the money.

PMID- 15851339
TI  - Comparison of stimulation sites within left ventricular veins on the acute
      hemodynamic effects of cardiac resynchronization therapy.
AB  - OBJECTIVES: The purpose of this study was to study the acute hemodynamic effect
      of left ventricular (LV) stimulation sites within a coronary vein. BACKGROUND:
      Access to LV stimulation sites for resynchronization therapy is achieved using
      specialized lead systems navigated through a coronary vein. The effects of
      stimulation in different coronary veins have been evaluated previously, but less
      is known about stimulation sites within a coronary vein. METHODS: Twenty-four
      patients (New York Heart Association functional class II-IV, age 59 +/- 10 years,
      ejection fraction 21 +/- 7%, QRS 166 +/- 30 ms) were enrolled in the study. A
      novel over-the-wire lead system was used to access an anterior or lateral
      coronary vein. At each lead location, a randomized stimulation protocol was
      executed. Hemodynamic responses were evaluated using LV dP/dtmax. RESULTS: The
      mean time to cannulate the coronary sinus and position the LV lead was 19 +/- 30
      minutes and 17 +/- 18 minutes, respectively. Data from stimulation at two sites
      within a coronary vein were obtained in 19 patients (anterior vein 11; lateral
      vein 8). Of these patients, 14 (anterior vein 9; lateral vein 5) showed large
      improvement in dP/dtmax (22%-25% in anterior vein, 37%-40% in lateral vein).
      Overall, there were no group differences in hemodynamic effects among different
      stimulation sites within a coronary vein, although significant variability among
      sites was observed in individuals. CONCLUSIONS: Resynchronization therapy through
      a coronary vein improves acute hemodynamic function of heart failure patients
      with LV conduction disorder. There were no significant differences between basal
      and apical pacing sites for this group.

PMID- 15851340
TI  - Prospective, randomized comparison of two biphasic waveforms for the efficacy and
      safety of transthoracic biphasic cardioversion of atrial fibrillation.
AB  - OBJECTIVES: The purpose of this study was to determine if there is a difference
      in commercially available biphasic waveforms. BACKGROUND: Although the
      superiority of biphasic over monophasic waveforms for external cardioversion of
      atrial fibrillation (AF) is established, the relative efficacy of available
      biphasic waveforms is less clear. METHODS: We compared the effectiveness of a
      biphasic truncated exponential (BTE) waveform and a biphasic rectilinear (BR)
      waveform for external cardioversion of AF. Patients (N = 188) with AF were
      randomized to receive transthoracic BR shocks (50, 75, 100, 120, 150, 200 J) or
      BTE shocks (50, 70, 100, 125, 150, 200, 300, 360 J). Shock strength was escalated
      until success or maximum energy dose was achieved. If maximum shock strength
      failed, patients received the maximum shock of the opposite waveform. Analysis
      included 141 patients (71 BR, 70 BTE; mean age 66.5 +/- 13.7. Forty-seven
      randomized patients were excluded because of flutter on precardioversion ECG upon
      blinded review (n = 25), presence of intracardiac thrombus (n = 7), or protocol
      deviation (n = 15). Groups were similar with regard to clinical and
      echocardiographic characteristics. RESULTS: The success rate was similar for the
      two waveforms (93% BR vs 97 BTE, P = .44), although cumulative selected and
      delivered energy was less in the BTE group. Only AF duration was significantly
      different between successful and unsuccessful patients. No significant
      complications occurred. CONCLUSIONS: Biphasic waveforms were very effective in
      transthoracic cardioversion of AF, and complication rates were low. No
      significant difference in efficacy was observed between BR and BTE waveforms.
      Impedance was not an important determinant of success for either biphasic
      waveform.

PMID- 15851341
TI  - Improved defibrillation efficacy with an ascending ramp waveform in humans.
AB  - OBJECTIVES: The purpose of this study was to compare an ascending ramp waveform
      (RAMP) with a standard, clinically available biphasic truncated exponential
      waveform (BTE) for defibrillation in humans. BACKGROUND: In animal studies, RAMP
      had a lower defibrillation threshold (DFT) than BTE. METHODS: We studied 63
      patients at implantable cardioverter-defibrillator placement using a dual-coil
      lead and left pectoral active can. The subjects were divided into two groups, one
      with a 12-ms ascending first phase and one with a 7-ms ascending first phase.
      Phase 2 of RAMP for both groups was a truncated exponential decay with 65% tilt
      and reversed polarity. The BTE had a 50% tilt in each phase. DFT and upper limit
      of vulnerability (ULV) were measured for both waveforms using a binary search
      protocol. RESULTS: The patient population was 77% male, with a mean age of 63 +/-
      10 years and ejection fraction of 33 +/- 13%. Delivered energy at DFT was lower
      with the 7-ms RAMP vs BTE (5.4 +/- 2.6 J vs 6.5 +/- 3.4 J; P < .01) but unchanged
      with the 12-ms RAMP (7.4 +/- 4.5 J vs 7.1 +/- 4.9 J). Maximal voltage at DFT was
      significantly lower with either RAMP compared to BTE (P < .01). There was a
      strong correlation between ULV and DFT for both RAMP and BTE (P < .01).
      CONCLUSIONS: The 7-ms ascending ramp waveform significantly reduced delivered
      energy (18%) and voltage (24%) at DFT, whereas the 12-ms RAMP reduced only DFT
      voltage. This is the first report of a waveform that is superior to a BTE for
      defibrillation in humans. ULV correlates with DFT for RAMP, supporting the use of
      ULV testing for implantation of devices.

PMID- 15851342
TI  - Ascending waveforms: The ramp to the Holy Grail?

PMID- 15851343
TI  - Microbubbles during radiofrequency catheter ablation: composition and formation.
AB  - OBJECTIVES: The purpose of this study was to measure tissue temperatures
      associated with microbubble formation during radiofrequency (RF) ablation.
      BACKGROUND: Microbubble formation visualized by echocardiography has been used to
      indicate excessive tissue heating during RF pulmonary vein isolation. However,
      little is known about the tissue temperatures associated with microbubble
      formation. METHODS: Optical fluorometric thermometry probes were used to record
      tissue temperatures in isolated porcine atrium overlying either lung or
      esophageal tissue in a saline bath. RF energy was delivered through an irrigated
      ablation electrode during echocardiographic monitoring for microbubble formation.
      RESULTS: The maximal recorded tissue temperatures were 81.0 +/- 5.0 degrees C and
      88.3 +/- 8.1 degrees C at the time of intermittent (type 1) microbubble formation
      for lung and esophageal preparations, respectively. During continuous (type 2)
      microbubble formation, the temperatures were 91.4 +/- 8.2 degrees C and 99.2 +/-
      7.8 degrees C, respectively (both P < .001 vs type 1). Tissue temperatures
      averaged >100 degrees C at the time of "pops." The maximal recorded temperature
      occurred up to 4 mm deep in the tissues and frequently occurred external to the
      atrial tissue. The total RF lesion volumes for lung and esophageal preparations
      were related to the pattern of microbubble formation but not to total power
      delivered. After generation of type 1 bubbles, up to 60% reductions in RF energy
      were needed to restore target tissue temperatures of 65 degrees C. Gas
      chromatographic analysis of the microbubbles was consistent with steam formation.
      CONCLUSIONS: Microbubble formation during RF ablation represents excessive tissue
      heating to the point of steam formation. Maximal tissue heating may occur in the
      adjacent lung and esophagus during cooled ablation.

PMID- 15851344
TI  - Atrial gradient as a potential predictor of atrial fibrillation.
AB  - OBJECTIVES: We tested the utility and comparability of the atrial gradient and
      atrial ERP as early markers of electrical remodeling and a propensity to atrial
      fibrillation (AF). BACKGROUND: Pacing at physiologic rates from the left atrium
      alters the atrial gradient and is associated with atrial tachyarrhythmias. At
      these physiologic rates, there is no change in the atrial effective refractory
      period (ERP). METHODS: Sixty-one chronically instrumented mongrel dogs in
      complete heart block were paced from the left or right atrium at 400 to 900 bpm
      for 46 +/- 3 days. Dogs were monitored weekly and electrophysiologic studies
      conducted to determine changes in the atrial gradient, ERP, and rhythm. RESULTS:
      Rapid atrial pacing was associated with concordant decreases in atrial gradient,
      ERP, and occurrence of AF. Incidence of AF increased with increasing pacing rate.
      Although there ultimately was an equal incidence of AF with left atrial and right
      atrial pacing, the onset of AF occurred earlier with left atrial pacing. As
      expected, ERP decreased in both atria. Animals with long control ERP did not
      fibrillate. CONCLUSIONS: Rapid pacing induces changes in atrial gradient, which
      can be used as a noninvasive marker of electrical remodeling. AF is accompanied
      by decreases in atrial gradient and ERP, and the incidence is highest in dogs
      with short control ERP.

PMID- 15851345
TI  - Prediction of atrial fibrillation: Role of the atrial gradient.

PMID- 15851346
TI  - Stereotactic catheter navigation using magnetic resonance image integration in
      the human heart.

PMID- 15851347
TI  - Short QT syndrome: successful prevention of sudden cardiac death in an adolescent
      by implantable cardioverter-defibrillator treatment for primary prophylaxis.

PMID- 15851349
TI  - Incessant tachycardia following catheter ablation of an accessory pathway: what
      is the mechanism?

PMID- 15851348
TI  - 15th annual Gordon K. Moe Lecture. Biological pacemaking: in our lifetime?

PMID- 15851350
TI  - Using the twelve-lead electrocardiogram to localize the site of origin of
      ventricular tachycardia.

PMID- 15851351
TI  - Visualization of cardiac resynchronization using real-time three-dimensional
      echocardiography.

PMID- 15851352
TI  - Recognition and prevention of commotio cordis.

PMID- 15851355
TI  - Automaticity in a Mahaim fiber.

PMID- 15851356
TI  - Relative alkali stability of some peptide o-phosphoserine and o-phosphothreonine
      esters.

PMID- 15851357
TI  - Radioguided techniques for parathyroid surgery.

PMID- 15851358
TI  - Prospective study comparing scrape cytology with frozen section in the
      intraoperative identification of parathyroid tissue.
AB  - OBJECTIVE: Intraoperative identification of parathyroid tissue is crucial during
      parathyroid surgery. Frozen section is the most common tool, but is time
      consuming and expensive. Scrape cytology is a modification of imprint cytology
      that provides rapid and cheap intraoperative identification of parathyroid
      tissue, but its reliability remains controversial. We assessed the sensitivity
      and specificity of scrape cytology in the intraoperative identification of
      parathyroid tissue. METHODS: Scrape cytology samples from parathyroid tissue
      (n=29), adipose tissue (n=3) and thyroid tissue (n=2) were prepared
      intraoperatively using May-Grunwald-Giemsa and Papanicolaou staining and
      subsequently sent for routine frozen section and standard paraffin section. A
      single pathologist reading the scrape cytology was blinded to the results of the
      frozen and standard paraffin sections. RESULTS: Scrape cytology identified 25 of
      29 parathyroid tissues, all three adipose tissues and one of two thyroid tissues.
      The remaining samples, four parathyroid tissues and one thyroid tissue, were not
      identified due to insufficient sample for diagnosis. The result translated to
      give a diagnostic accuracy of 88.2%, sensitivity of 86%, and specificity of 100%.
      All tissues were accurately identified by frozen section. CONCLUSION: Scrape
      cytology is a rapid, economical test with acceptable sensitivity and high
      specificity. It can be used as an adjunct to frozen section and may be used as a
      tool in helping surgeons to identify parathyroid tissue.

PMID- 15851359
TI  - Use of the electrothermal vessel sealing system versus standard vessel ligation
      in thyroidectomy.
AB  - OBJECTIVE: The electrothermal vessel sealing system (LigaSure) facilitates
      operative haemostasis by fusing blood vessel walls to form a collagen seal. The
      LigaSure is currently used in a variety of gastrointestinal, gynaecological and
      urological operations. We report our experience with LigaSure for thyroidectomy
      to test the hypothesis that it reduces operating time without increasing
      complications compared with standard vessel ligation. METHODS: This non
      randomized, retrospective review included 234 consecutive patients who underwent
      thyroidectomy by one surgeon. Standard vessel ligation was used in 99 patients
      between 1997 and 2000, and the LigaSure was used in 135 patients between 2001 and
      2003. The following data were collected: patient demographics, thyroid pathology,
      type of operation (total thyroidectomy vs lobectomy), operating time,
      complications (transient or permanent hypocalcaemia, <or=8 mg/dL), recurrent or
      superior laryngeal nerve injury, neck haematoma, wound complications, prolonged
      intubation), incision length and hospital stay. RESULTS: The two groups had
      similar demographics, thyroid pathology, types of operations and complication
      rates. The LigaSure group had lower operating times and incision lengths.
      CONCLUSION: We found that the LigaSure was as safe as standard vessel ligation
      for thyroidectomy, with the benefit of reduced operating time. A future
      prospective study has been designed.

PMID- 15851360
TI  - Pre-ablative diagnostic whole-body scan following total thyroidectomy for well
      differentiated thyroid cancer: is it necessary?
AB  - OBJECTIVE: This study reviewed the incidence of positive pre-ablative diagnostic
      scan after total thyroidectomy and the efficacy of the current ablative dose. The
      predictive factors for outcome using a standard ablative dose and postoperative
      complications of total thyroidectomy were also examined. METHODS: This was a
      retrospective review of patients referred for radioiodine ablation after total
      thyroidectomy between September 1997 and September 2001. RESULTS: Forty patients
      were included in this study, of whom 95% had a positive scan after total
      thyroidectomy. Of the 30 patients who underwent standard 80-mCi radioiodine
      ablation, 21 (70%) had successful single ablation while the remaining nine
      patients needed a higher ablative dose. There were no significant differences
      between patients who had successful ablation with the standard dose and those who
      did not in terms of tumour size, patient age, lymph node status and extra
      thyroidal extension. Fifteen percent suffered from permanent hypoparathyroidism
      requiring calcium supplementation. Three patients had documented recurrent
      laryngeal nerve paralysis. CONCLUSION: Bypassing the pre-ablative diagnostic scan
      is feasible. The present ablation dose of 80 mCi of radioiodine is effective. The
      relatively high postoperative morbidity after difficult total thyroidectomy
      suggests less aggressive excision and postoperative radioiodine ablation of the
      remnant tissue.

PMID- 15851361
TI  - Correlation between breast tumour size and level of axillary lymph node
      involvement.
AB  - OBJECTIVE: Axillary lymph node dissection (ALND) is important for prognosis but
      does carry certain morbidities, particularly arm lymphoedema. Our aim was to
      determine whether tumour size correlates with level of axillary lymph node
      involvement in order to minimize ALND for small tumours. METHODS: Data were
      collected prospectively. Patients undergoing breast cancer surgery between May
      and December 2002 underwent preoperative breast ultrasound to measure the size of
      the primary tumour. Standard ALND was performed for all patients and levels of
      lymph nodes were sent separately to determine extent of involvement. RESULTS: Of
      the 203 cases studied, 91 (44.8%) had T1 tumours (<2 cm). The incidence of level
      II lymph nodes in T1 tumours was 4.4% (4/91 patients). The greater the T stage,
      the higher the incidence of level I and II involvement (4.4% in T1, 7.1% in T2
      and 36.5% in T3 tumours). No node-positive patients had isolated level II lymph
      node involvement. Ultrasound-determined tumour size correlated well with final
      histological size (p<0.0005). CONCLUSION: Based on size, 95.6% (87/91) of
      patients with T1 tumours did not have level II lymph node metastases, so for
      these patients, level I axillary dissection is adequate.

PMID- 15851362
TI  - Dissection with a metal dissector: a useful adjunct to transhiatal
      oesophagectomy.
AB  - OBJECTIVE: Intraoperative cardiovascular instability is frequently observed
      during blunt finger dissection for transhiatal oesophagectomy. We conducted a
      prospective study using a metal ring dissector for blunt dissection of the
      oesophagus to overcome this problem. METHODS: Dissection with a metal ring
      dissector was used in 30 consecutive patients undergoing transhiatal
      oesophagectomy for carcinoma of the lower oesophagus (n=26) and oesophagogastric
      junction (n=4). RESULTS: Dissection of the oesophagus proximal to the growth was
      quick and straightforward in all instances. The procedure appeared less traumatic
      than the conventional manual technique and was not associated with any
      intraoperative cardiovascular instability or intramediastinal bleeding. None of
      the patients had tracheal injury or recurrent laryngeal nerve paralysis. There
      was one anastomotic leak and no deaths. CONCLUSION: Oesophageal blunt dissection
      with a metal ring dissector is safe, easy and quick. The correct plane of
      dissection minimizes the risk of intramediastinal bleeding and inadvertent trauma
      to neighbouring structures.

PMID- 15851363
TI  - Appropriate antibiotic administration in elective surgical procedures: still
      missing the message.
AB  - OBJECTIVE: The aim of this study was to determine the appropriateness of
      antibiotic prophylaxis in selected elective surgical procedures in a tertiary
      referral centre. METHODS: A cross-sectional study using retrospective data from
      January 2000 to May 2002 was performed pertaining to elective colorectal surgery,
      cholecystectomy and inguinal hernia repairs. Appropriateness of antibiotic
      administration was determined based on compliance with national and
      internationally accepted guidelines on prophylactic antibiotic prescribing
      policy. A single dose or omission of antibiotic administration was judged
      appropriate for cholecystectomy and inguinal hernia repair, while up to 24 hours'
      dosing was considered appropriate practice for colorectal surgery. RESULTS: Of
      419 cases, there were 55 (13.1%) colorectal procedures, 97 (23.2%)
      cholecystectomies and 267 (63.7%) inguinal hernia repairs. Antibiotics were
      administered in a total of 306 (73%) cases, with single-dose prophylaxis in only
      125 (41%) of these. Prophylaxis was inappropriately prolonged in 80%, 52% and 31%
      of colorectal, cholecystectomy and inguinal hernia cases, respectively. The
      corresponding mean duration of anti-biotic administration was 2.4+/-2.2, 1.6+/
      1.8 and 1.1+/-1.3 days, respectively. CONCLUSION: Antibiotic prophylaxis in
      elective surgery continues to be administered haphazardly. This study supports
      close surveillance of antibiotic utilization by a dedicated team, perhaps
      consisting of microbiologists or pharmacists, to minimize inappropriate
      administration.

PMID- 15851364
TI  - Retained surgical sponges (gossypiboma).
AB  - OBJECTIVE: Retained surgical sponges are seldom reported due to medicolegal
      implications. Awareness of this problem among surgeons and radiologists is
      essential to avoid unnecessary morbidity. We present our experience with this
      entity and review the related literature. METHODS: The medical records of 11
      patients who were diagnosed as having retained surgical sponges from 1990 to 2003
      were reviewed. RESULTS: The incidence was 1:5,027 inpatient operations. There
      were four males and seven females with a median age of 45 years. The original
      operations were gynaecological (n=4), general (n=4), urological (n=2) and
      laminectomy (n=1). In seven cases, the original operation was performed on an
      emergency basis. Five patients were obese. A presumed correct sponge count was
      documented in eight cases. The median time between the original procedure and
      diagnosis of retained sponges was 12 months. The tentative diagnosis was
      intestinal obstruction (4 patients), urinary tract infection (1 patient), Crohn's
      disease (1 patient) and tumour recurrence (1 patient). The correct diagnosis was
      suggested in the remaining four patients. Surgical removal of the retained
      sponges was carried out in all cases except one, in which the patient passed the
      sponge spontaneously through the rectum. CONCLUSION: Retained sponges are more
      common in obese patients and after emergency surgery. A high degree of suspicion
      is important for preoperative diagnosis. Despite the use of radio-opaque sponges
      and thorough sponge counting, this moribund mishap still occurs. Although human
      errors cannot be completely abolished, continuous medical training and strict
      adherence to regulations should reduce the incidence to a minimum.

PMID- 15851365
TI  - Lymph node counts in indians in relation to lymphadenectomy for carcinoma of the
      oesophagus and stomach.
AB  - OBJECTIVE: Systemic lymphadenectomy for carcinoma of the oesophagus and stomach
      is increasingly accepted as effective surgical treatment. A review of available
      literature reveals a great variety in the number of lymph nodes removed during
      standard lymphadenectomy. The present study was conducted to find the normal
      number of lymph nodes in the Indian population in relation to lymphadenectomy for
      oesophageal and gastric carcinoma. METHODS: Lymph nodes situated at stations 1
      16, relevant to lymphadenectomy for gastric cancer, were removed by lymph node
      dissection according to the recommendations of the Japanese Research Society for
      Gastric Cancer and those at the 22 stations, relevant to lymphadenectomy in
      oesophageal cancer, were removed according to the International Society for
      Diseases of the Esophagus recommendations in 10 cadavers without a history of any
      abdominal pathology or haematological lymphatic disease. Nodes were cleared by
      dissolving fatty tissue. All lymph nodes were histologically confirmed and the
      diameter of each lymph node was recorded. RESULTS: An average of 52.0 nodes
      (range, 37-78 nodes) was found at Stations 1-16, while an average of 183.6 nodes
      (range, 118-234 nodes) was found at the 22 stations. These numbers are higher
      than those in the literature. CONCLUSION: This anatomical study addresses the
      dual issues of determining the number of dissectable lymph nodes in a particular
      population as well as assessing the quality of nodal dissection by providing
      quantitative surgical guidelines.

PMID- 15851366
TI  - Role of enteral immunonutrition in patients with gastric carcinoma undergoing
      major surgery.
AB  - OBJECTIVE: To evaluate the influence of postoperative immunonutrition on immune
      and nutritional parameters in patients with gastric carcinoma. METHODS: From
      September 2002 to August 2003, 40 patients with gastric carcinoma who had
      undergone major surgery were randomly divided into an immunonutrition group and
      standard nutrition group, each of 20 patients. On postoperative Day 2, patients
      in the standard nutrition group received a standard enteral formula, while those
      in the immunonutrition group received an enteral formula enriched with glutamine,
      arginine and omega-3 fatty acids. Nutritional support was continued for 7 days.
      Blood samples were obtained to determine plasma albumin, prealbumin and
      transferrin on Days 0, 5 and 9. On Days 0, 1 and 9, blood samples were collected
      to detect immunoglobulin (Ig) A, IgG, IgM, CD4 and CD8 cell counts, the ratio of
      CD4/CD8, interleukin (IL)-2, IL-6 and tumour necrosis factor (TNF)-alpha,
      respectively. RESULTS: There were no significant differences between the two
      groups in protein and immune parameters preoperatively and no significant
      differences in management perioperatively. No serious adverse effects were
      recorded with the two formulas. Postoperative procedures were smooth in both
      groups. On Day 9, serum levels of prealbumin and transferrin were higher in the
      immunonutrition group than in the standard nutrition group (p<0.01). After 7
      days' nutritional support, patients in the immunonutrition group had higher
      levels of immunoglobulin, CD4 cell counts, CD4/CD8 ratio and IL-2 than those in
      the control group, whereas IL-6 and TNF-alpha levels were significantly lower in
      the immunonutrition group. CONCLUSION: Compared with standard enteral nutrition,
      enteral immunonutrition can improve defence mechanisms and modulate inflammatory
      action after major elective surgery for gastric carcinoma.

PMID- 15851367
TI  - Venous thromboembolic disease prophylaxis among general surgeons in Malaysia.
AB  - OBJECTIVE: The aim of this study was to analyse the current practice of venous
      thromboembolism (VTE) prophylaxis among general surgeons in Malaysia. METHODS: A
      questionnaire survey was conducted among general surgeons attending the annual
      Malaysian College of Surgeons meeting in 2002. A total of 110 questionnaires were
      distributed to specialist-grade general surgeons with varying subspecialty
      interests. RESULTS: Seventy-seven (70%) surgeons returned the questionnaire. Of
      these, 43% were of the opinion that VTE was as common in Asian patients as in the
      West. Selective VTE prophylaxis was used by 99% in their practice. The
      indications for use, in order of frequency, were: previous VTE disease, risk
      grading, prolonged surgery, obesity, malignancy and age. Low molecular weight
      heparin was the most common type of prophylaxis used. VTE-related morbidity was
      reported by 44 surgeons (57%) over the past year, and 39% of these cases were
      fatal. CONCLUSION: The high incidence of VTE-related complications indicates that
      the use of thromboprophylaxis is either insufficient or not matched to the level
      of risk. Updated guidelines on VTE prophylaxis should be used so that a
      standardized approach can ensure that patients receive adequate prophylaxis where
      indicated.

PMID- 15851368
TI  - Diagnostic value of blood D-dimer level in acute mesenteric ischaemia in the rat:
      an experimental study.
AB  - OBJECTIVE: The high mortality rate of mesenteric ischaemia is mainly due to delay
      in diagnosis. For this reason, it is of great importance to find a specific and
      rapidly elevating marker. The present study investigated the diagnostic value of
      blood D-dimer level as a potential marker for acute mesenteric ischaemia in a rat
      model. METHODS: Thirty male Wistar albino rats were divided into three groups.
      Basal D-dimer and L-lactate levels were determined in the non-operative control
      group (I). In the operated control group (II), the superior mesenteric artery was
      simply manipulated, while the artery was ligated in Group III. Blood samples were
      drawn in all groups for D-dimer and L-lactate assays. RESULTS: Both Group II
      (p=0.016) and Group III (p=0.001) had significantly higher mean D-dimer levels in
      the first postoperative hour compared with the basal level in Group I. However,
      there was no difference between the levels in Groups II and III. The mean level
      in Group II in the sixth hour had dropped to a statistically insignificant level
      compared with the basal value, while the mean value in Group III kept rising
      during this period (p=0.001). Nevertheless, there was no significant difference
      between Groups II and III. On the other hand, the mean L-lactate level in the
      first postoperative hour in Group III was significantly higher than the basal
      level in Group I (p=0.003). No significant rises were recorded in Group II in the
      first and sixth postoperative hours. The difference between Groups II and III in
      the first hour was significant (p=0.005). Group III also had significantly higher
      mean serum L-lactate value in the sixth hour compared with both the basal value
      in Group I (p=0.001) and the sixth-hour value in Group II (p=0.003). CONCLUSION:
      These results do not adequately support the use of blood D-dimer level as an
      independent parameter in the diagnosis of mesenteric ischaemia due to arterial
      thrombosis. However, this parameter can be used together with other tests in
      eliminating the possibility of a thromboembolic event.

PMID- 15851369
TI  - Migratory foreign body in the neck.
AB  - Oesophageal penetration and migration of foreign bodies are fairly rare
      occurrences. Most reported cases in the literature involve fish bones, which are
      eventually found in the lateral neck soft tissue or thyroid lobule. We present a
      case of a migrating fish bone in an elderly female which was found embedded in
      her right sternocleidomastoid muscle. The fish bone was successfully removed via
      neck exploration. Appropriate literature is reviewed.

PMID- 15851370
TI  - Mucosal repair of posterior perforation of duodenal diverticulitis using roux
      loop duodenojejunostomy.
AB  - Perforation of duodenal diverticulum is a rare occurrence but has a potentially
      fatal outcome. It is a difficult surgical problem because of delayed diagnosis
      and the attendant risk of duodenal fistula following primary repair. We present a
      case of posterior perforation of duodenal diverticulitis, diagnosed on computed
      tomography and successfully repaired with a Roux loop duodenojejunostomy. We also
      discuss the rare pathology, diagnosis and surgical options with special reference
      to this alternative form of mucosal repair.

PMID- 15851371
TI  - Treatment of delayed chylothorax complicating oesophagectomy.
AB  - A patient with carcinoma of the cardia underwent Ivor-Lewis oesophagogastrectomy.
      He developed right chylothorax postoperatively, which is a rare complication.
      Attempts to treat the chylothorax by conservative means and thoracoscopic
      ligation failed. Finally, pleurodesis using bleomycin successfully sealed the
      leak and he was discharged.

PMID- 15851372
TI  - Laparoscopic repair of diaphragmatic hernias: experience of six cases.
AB  - OBJECTIVE: Laparoscopic diaphragmatic hernia repair is increasingly performed in
      adults for congenital diaphragmatic hernias and chronic traumatic diaphragmatic
      hernias. This study reviewed our experience with laparoscopic diaphragmatic
      hernia repair to evaluate its safety, efficacy and outcomes. METHODS: Between
      January 1999 and December 2002, four male and two female patients presented to us
      with diaphragmatic hernias, three with traumatic and three with congenital
      hernias. The mean age of patients was 58.6 years (range, 42-83 years). Five
      patients presented with main complaints of postprandial retrosternal/chest
      discomfort and one patient had an acute gastric outlet obstruction. Dissection
      was performed laparoscopically to reduce the contents of the sac and the hernial
      defect was repaired using prolene sutures and a polypropylene mesh. RESULTS:
      Laparoscopic repair of diaphragmatic hernias was completed successfully in all
      patients. The mean size of the defect was 6.8 cm (range, 3-12 cm) and the mean
      operative time was 100 minutes (range, 60-150 minutes). There were no major
      intraoperative complications. One patient required placement of a chest tube due
      to inadvertent opening of the pleura with the hernial sac and one patient had
      prolonged postoperative gastric ileus. The mean hospital stay was 2.3 days
      (range, 1-4 days) and the mean pain score was 4 (range, 2-6). All patients
      remained asymptomatic over a mean follow-up of 2.9 years. CONCLUSION: Adult
      congenital and chronic traumatic diaphragmatic hernias are amenable to
      laparoscopic repair. Laparoscopic repair is safe and feasible and confers all the
      advantages of minimal access surgery.

PMID- 15851373
TI  - Rapid microwave ablation of large hepatocellular carcinoma in a high-risk
      patient.
AB  - A 74-year-old male with an inoperable, large (6 cm in diameter) primary
      hepatocellular carcinoma of the liver was successfully treated using a novel
      microwave ablating system. Using a single applicator, the tumour was treated at
      150 W for 4 minutes. An ablation zone 8 cm in diameter was achieved, which
      gradually shrunk to form scar tissue that remained unchanged without tumour
      recurrence for 2 years.

PMID- 15851374
TI  - Biliary atresia associated with jejunal atresia and a review of the literature in
      Japan.
AB  - An unusual case of biliary atresia with jejunal atresia is herein described. Only
      12 cases demonstrating biliary atresia associated with a jejunal atresia have
      been previously reported in Japan. The pathogenesis of biliary atresia is thought
      to be secondary to the influence of jejunal atresia.

PMID- 15851375
TI  - Skin disorders in association with monoclonal gammopathies.
AB  - Monoclonal gammopathy represents a condition characterized by clonal
      proliferation and accumulation of immunoglobulin producing B-cells. A variety of
      skin disorders are associated with an increased level of monoclonal
      immunoglobulin proteins. These skin disorders can be divided into two groups. The
      first group represents a direct consequence of plasma cell proliferation. The
      colonization of the plasma cell clone in the dermis expressed as a deposition of
      proteins related to the M component belongs to this group for which the
      pathogenesis is well identified, as is the case for example with AL amyloidosis
      and cryoglobulins. The second group represents skin disorders such as
      scleromyxedema and Schnitzler syndrome that are highly associated with an M
      component, or diseases such as pyoderma gangrenosum and leukocytoclastic
      vasculitis that are more weakly associated with increased levels of monoclonal
      immunoglobulins. In some other dermatoses such as pemphigus, bullous pemphigoid,
      epidermolysis bullosa aquisita, Sezary syndrome, lymphomatoid papulosis,
      urticaria pigmentosa, and acquired ichthyosis, only presumptions exist regarding
      associations with monoclonal gammopathies. In this the pathogenesis, therapy and
      prognosis of the most relevant dermatoses shall be described in order of their
      degree of association with monoclonal gammopathies, which shall also be
      discussed.

PMID- 15851376
TI  - Low dose prednisolone reduces CD4+ T cell loss in therapy-naive HIV-patients
      without antiretroviral therapy.
AB  - BACKGROUND: A favorable development of CD4+ T cells was noticed in therapy-naive
      HIV-patients without antiretroviral therapy (ART) taking 5 mg prednisolone daily.
      Based on these encouraging observations, prednisolone therapy in further HIV
      patients without antiretroviral therapy was initiated. OBJECTIVE: To evaluate the
      effect of low dose prednisolone on therapy-naive HIV patients without
      antiretroviral therapy. METHODS: A retrospective analysis has been conducted
      comparing the development of CD4+ T cells, viral load and clinical outcome in all
      therapy-naive HIV-patients with (n = 65; CD4 > or =300/microl) or without (n =
      136; CD4 > or =300/microl) prednisolone treatment for > or =6 months. RESULTS:
      After 3 years, therapy-naive patients on prednisolone therapy showed a CD4+ T
      cell increase of +50.1/microl whereas in the untreated group a decrease of 
      186.1/microl (p = 0.0021) was noted. After 12 months, nearly twice as much
      untreated patients experienced a first-time CD4+ T cell loss of >100/microl or
      initiation of HAART due to clinical development compared to prednisolone-treated
      patients (64.1% vs. 35.0%). CD4+ T cell increase was associated with viral load
      at baseline: Patients with lower viral loads at baseline (<30,000 copies/ml)
      showed a favorable development with statistically significant less drop-outs
      (defined as HAART-onset and/or prednisolone discontinuation for the prednisolone
      group) than patients with higher viral loads at baseline in the first 3 years in
      the prednisolone group. - CONCLUSION: Low dose prednisolone seems to be
      associated with a stabilization of CD4+ T cell count in therapy-naive HIV
      patients resulting in a pronounced prolongation of the potential time without
      HAART for many HIV patients.

PMID- 15851378
TI  - Association of RANTES with the replication of severe acute respiratory syndrome
      coronavirus in THP-1 cells.
AB  - BACKGROUND: Severe acute respiratory syndrome (SARS) is a novel infectious
      disease which is characterized by an overaggressive immune response. Chemokines
      are important inflammatory mediators and regulate disease due to viral infection.
      In previous study, we found that SARS-CoV has the ability to replicate in
      mononuclear cells. In present work, we sought to characterize the replication of
      SARS-CoV at the presence of RANTES in THP-1 cells. METHODS: To determine whether
      RANTES play an role in the process of SARS, THP-1 cells were incubated with heat
      inactivated SARS-CoV and ELISA was used to test RANTES levels in the
      supernatants; Then the effect of dexamethasone on the induced secretion was
      evaluated. Real-time PCR was used to investigate the effort of RANTES on the
      replication of SARS-CoV in vitro. Macrophages, induced by THP-1 cells, were used
      as cell model. FINDINGS: Inactive SARS-CoV could induce THP-1 cells secret RANTES
      and this increase effect could not be suppressed by DXM. RANTES itself could
      inhibit the replication of SARS-CoV in THP-1 cells when it was added into the
      culture before or at the same time with the virus; No inhibition effect was shown
      when RANTES were added into the culture after SARS-CoV infected the cells.

PMID- 15851377
TI  - FK506 enhances triptolide-induced down-regulation of cyclooxygenase-2, inducible
      nitric oxide synthase as well as their products PGE2 and NO in TNF-alpha
      stimulated synovial fibroblasts from rheumatoid arthritic patients.
AB  - OBJECTIVE: To explore the effects of FK506 on the inhibition of cell
      proliferation and the expression of cyclooxygenase-2 (COX-2), inducible nitric
      oxide synthase (iNOS) and their products PGE subset2 and NO in TNF-alpha
      stimulated human rheumatoid arthritis synovial fibroblasts (RASF) treated with
      triptolide (TP), and to study the mechanisms involved when combining FK506 and TP
      in RA therapy. MATERIALS AND METHODS: RASF used in the experiments were obtained
      from the synovial tissue of patients with RA before being cultured. RASF were
      pretreated with FK506 (10 approximately 1000 nM) for 2 hours before being
      stimulated with TNF-alpha (20 ng/ml) in the presence or absence of TP (10 ng/ml)
      . RASF proliferation was determined by [3 supersetH]-TdR incorporation.
      Production of PGE subset2 and NO in culture supernatants of RASF was detected by
      competitive ELISA and enzymatic reduction of nitrate, respectively. Expressions
      of COX-2 and iNOS mRNA in RASF were analyzed by semi-quantitative RT-PCR.
      Expressions of COX-2 and iNOS protein were estimated by Western-blot and a
      cellular enzyme immunoassay. NFkappaB activity in whole-cell extract of treated
      RASF was also measured using an ELISA-based method. RESULTS: Neither FK506 nor TP
      at a lower concentration (10 ng/ml) affected TNF-alpha-induced COX-2 and iNOS
      expressions or PGE subset2 and NO productions in synovial cells. Combined
      treatment of FK506 and a lower concentration of TP (10 ng/ml) reduced both COX-2
      and iNOS mRNA and protein expression, and correspondingly reduced PGE subset2 and
      NO produced by synovial fibroblasts. This effect was highly correlated with FK506
      concentration (10 approximately 1000 nM). NFkappaB activity in TNF-alpha
      stimulated synovial cells was suppressed more profoundly by FK506 plus TP (10
      ng/ml) than by TP (10 ng/ml) alone. However, no change was observed regarding the
      inhibition of synovial cell proliferation after combined treatment of FK506 and
      TP. CONCLUSION: FK506 enhanced TP-mediated down-regulation of COX-2 and iNOS as
      well as their products PGE subset2 and NO in human TNF-alpha-stimulated RASF by
      more profoundly suppressing the activity of NFkappaB.

PMID- 15851379
TI  - Inguinal Hernia: classification, diagnosis and treatment--classic, traumatic and
      Sportsman's hernia.
AB  - Inguinal hernia repair is performed in more than 600,000 cases every year in the
      United States. However, the true prevalence may be even higher. Many groin
      hernias are not diagnosed, e.g., Sportmans' hernia, or are asymptomatic. The
      etiology of classic inguinal hernia, Sportsman's hernia or traumatic hernia may
      be different. The hernia repair is performed in agreement with a classification
      of the hernia, e.g., Nyhus classification. According to recent randomized
      controlled trials and meta-analyses open-mesh repair demonstrates several
      advantages in comparison to laparoscopic procedures. Laparoscopic procedures
      require more time and cost more, show a potential for serious complications and
      may be followed by an increased rate of recurrence. There may be a faster
      reconvalescence after laparoscopic procedures. However, there may be also a
      selection bias. Laparoscopic procedures are associated with specific
      complications, e.g., pneumomediastinum, pneumothorax, gas extravasation, trocar
      injuries, intraabdominal adhesions, bowel obstruction, which are rarely or never
      seen in open-mesh repair. In the United States we could observe an uncoupling of
      hernia repair from classification. In more than 90% of cases the treatment was
      open-mesh. In many hernia studies the hernias were classified as direct or
      indirect, primary or recurrent. The existing classifications are based on
      anatomical findings in relation to the development of the hernia: posterior floor
      integrity, enlarged interior ring and size of the hernia. However, the size of
      the hernia may not always be associated with the severity of the hernia and it
      may be difficult to estimate. The outcome of hernia repair may be influenced by
      other factors. There may be differences in the presentation of the hernia to the
      surgeon based on the damage done to the surrounding tissue in the inguinal canal,
      e.g., external ring, aponeurosis of the external oblique, inguinal ligament,
      which is most often accompanied by severe adhesions. Further factors influencing
      outcome of hernia repair may be patient-related factors, e.g., constipation, ASA
      classification, diabetes, smoking. A classification should be simple to use and
      easy to remember: (A) indirect hernia, (B) direct hernia, (C) scrotal or giant
      hernia, (D) femoral hernia. A and B can be classified as (0) uncomplicated, (1)
      posterior floor defect, (2) posterior floor defect plus defect in the anterior
      part of the inguinal canal. All four types (A-D) may be either primary or
      recurrent. In this classification combined femoral, indirect and/or direct
      hernias can be categorized by using the types A, B, C, or D as in a modular
      construction system. The category "other" is reserved for rare types of hernia,
      e.g., obturator hernia, Spieghelian hernia. Aggravating factors are included:
      Diabetes, obesity, age above 65, constipation, ASA III or more and cigarette
      smoking. This classification may be helpful to evaluate outcome of hernia repair
      with regard to patient related factors and the increased demands for the surgeon
      and the staff. In some health care systems the general belief is that all hernias
      are equal and be managed equally. However, groin hernias may be complex and need
      individual treatment.

PMID- 15851380
TI  - Duodenal somatostatinoma: clinical and immunohistochemical patterns--difficult
      differential diagnosis in regard to gangliocytic paraganglioma: report of a case.
AB  - The authors report a large duodenal somatostatinoma, a very rare tumor entity. A
      8.5 cm globular mass in the area of the unicate process of the pancreas was
      detected in a 45 year old caucasian female by computerized tomography. The
      patient had only mild complaints. Initial treatment consisted of right
      pancreatectomy with preservation of the pylorus. Histological evaluation rendered
      a diagnosis of low-grade malignant neuroendocrine carcinoma with expression of
      somatostatin, respectively of somatostatinoma arising in the duodenum and
      infiltrating into the pancreas. 26 months after the initial surgery liver and
      lymph node metastases were detected and surgically removed. This case confirms
      that duodenal somatostatinomas are very difficult to diagnose preoperatively
      because of unspecific symptoms. Most duodenal somatostatinomas are found
      incidentally. Treatment of choice is radical surgical resection with a possible
      cure in early stages of the disease. Even a large tumor as ours is resectable
      with negative surgical margins. Management of recurrent or metastatic disease is
      also surgical. Additional chemotherapy and supportive care may be beneficial for
      the patient.

PMID- 15851381
TI  - Prognostic significance of syndecan-1 expression in human endometrial cancer.
AB  - BACKGROUND: Syndecan-1 binds to various extracellular matrix components via its
      heparan sulfate glycosaminoglycans. The aim of this study was to investigate
      syndecan-1 expression in endometrial cancers. PATIENTS AND METHODS: We
      investigated the expression of the syndecan-1 core protein by
      immunohistochemistry in 109 endometrial cancers, and analyzed correlation with
      various clinicopathological features, including patient outcome. RESULTS:
      Epithelial syndecan-1 expression was significantly lower in advanced stage, high
      grade, deep myometrial invasion, cervical involvement, lymph node metastasis,
      lymph vascular space involvement and positive peritoneal cytology. Stromal
      syndecan-1 expression was significantly higher in high-grade tumors. The disease
      free and overall survival rates of patients exhibiting both low epithelial and
      high stromal syndecan-1 expression was poor. Multivariate analysis showed that
      high stromal syndecan-1 expression was an independent prognostic factor for both
      disease-free and overall survival. Low epithelial syndecan-1 expression was a
      prognostic factor only in the univariate analysis. CONCLUSIONS: Loss of
      epithelial syndecan-1 and induction of stromal syndecan-1 expression may be
      associated with tumor progression. Stromal syndecan-1 expression can serve as an
      indicator of poor prognosis in patients with endometrial cancer.

PMID- 15851382
TI  - Teaching the interdisciplinary nature of quality.

PMID- 15851383
TI  - Reducing excessive medication administration in hospitalized adults with renal
      dysfunction.
AB  - Medication errors are common and harm hospitalized patients. The authors designed
      and implemented an automated system to complement an existing computerized order
      entry system by detecting the administration of excessive doses of medication to
      adult in-patients with renal insufficiency. Its impact, in combination with
      feedback to prescribers, was evaluated in 3 participating nursing units and
      compared with the remainder of a tertiary care academic medical center. The
      baseline rate of excessive dosing was 23.2% of administered medications requiring
      adjustment for renal insufficiency given to patients with renal impairment on the
      participating units and 23.6% in the rest of the hospital. The rate fell to 17.3%
      with nurse feedback and 16.8% with pharmacist feedback in the participating units
      (P<.05 for each, relative to baseline). The rates of excessive dosing for the
      same time periods were 26.1% and 24.8% in the rest of the hospital. Automated
      detection and routine feedback can reduce the rate of excessive administration of
      medication in hospitalized adults with renal insufficiency.

PMID- 15851384
TI  - Attitudes about patient safety: a survey of physicians-in-training.
AB  - Little is known about the attitudes of physicians-in-training on patient safety,
      although success in error reduction strategies requires their support. We
      surveyed house staff and fourth-year medical students from 1 academic institution
      about their perceptions of adverse patient events. Three hundred twenty-one
      trainees (41%) completed the survey. Most believe adverse events are preventable
      (61%) and think improved teamwork (88%), better procedural training (74%), and
      improved sign-out (70%) would reduce medical mishaps. Forty-seven percent of
      trainees agree computerized order entry and restricted work hours would prevent
      adverse events. Although 60% feel malpractice fears inhibit discussion, 80% of
      trainees agreed physicians must disclose adverse events to patients and grow more
      comfortable with disclosure as training progresses (P for trend<.01). In
      conclusion, trainees believe adverse events are preventable and are poised to
      respond to many components of the patient safety movement.

PMID- 15851385
TI  - Have you wondered about your colleague's surgical skills?
AB  - Surgical skills are important for surgical competence. Surgical skills may be
      assessed during residency but are not routinely evaluated in practicing surgeons.
      The current literature is reviewed to evaluate models for objectively assessing
      surgical skills. Since most studies evaluate models as teaching tools, some
      extrapolations are necessary. Based on the current literature, recommendations
      are made for adapting physical models and computer simulations to a program for
      surgical skills monitoring and remediation for practicing surgeons.

PMID- 15851386
TI  - The role of a clinical pathway in curtailing unnecessary investigations in
      children with gastroenteritis.
AB  - Clinical pathways are useful tools in improving the quality of care of patients
      treated in hospitals. Gastroenteritis is a short, self-limiting, but common
      illness of childhood associated with significant costs to the community. The
      authors assessed the impact of a clinical pathway on investigation ordering in
      children with gastroenteritis. A retrospective analysis of 2 cohorts of children
      was performed before (n=1498) and after (n=1252) the introduction of a clinical
      pathway. Children admitted to hospital with a diagnosis of gastroenteritis were
      assessed as to the type of pathology tests ordered. Further outcomes measured
      were rates of admission, emergency department presentations, average length of
      stay, and direct costs. Subset analysis was undertaken on the initial cohort of
      patients who had a full blood count as part of their initial assessment. Full
      blood count was more likely to be performed prior to the introduction of the
      pathway(77.1%) than after pathway introduction (66.8%; P<.004). Urine microscopy
      and culture also was significantly decreased from 56.3% to 40.4% (P<.0005).
      Median patient costs were reduced from $1228 to $752 following pathway
      introduction (P<.0001); however, rates of admission were increased from 18.6% to
      28.8% (P<.0001). Length of stay decreased but was not statistically significant.
      Full blood count results in the subset analysis revealed that the measurement of
      a full blood count had no impact on management. Thus, a clinical pathway
      contributed to more rational ordering of pathology tests and lowered the costs to
      a hospital of caring for patients with this common illness.

PMID- 15851387
TI  - Appropriate admissions to the appropriate unit: a decision tree approach.
AB  - An intermediate care decision tree tool was developed to meet the demand for
      intermediate care beds. Concurrently, a charging process was developed to support
      the acuity adaptable model of care, allowing the patient to remain in the same
      bed from admission to discharge, regardless of level of care required, adjusting
      nurse-to-patient ratios as acuity changes. Since beginning this pilot, 96% to
      100% of the patients admitted to intermediate care from the emergency department
      met the criteria. Wait time from request to admission was reduced from 5.5 hours
      to 2.5 hours. A reduction in nursing costs was noted. The average number of
      patients waiting daily in the emergency department for an intermediate care bed
      has been reduced by approximately 80%. A significant difference in length of stay
      was not noted.

PMID- 15851388
TI  - Case study: a medicaid health maintenance organization quality initiative for
      behavioral health.
AB  - The purpose of this case study is to assess a Medicaid health maintenance
      organization quality initiative designed to screen new members for behavioral
      health treatment needs on enrollment. New members were screened by the health
      maintenance organization, which then informed the for-profit managed care
      organization responsible for the management of the mental health and substance
      abuse benefit of its findings. Other than the screening, there were no
      contractual expectations. The managed care organization was given only the names
      of individuals who "screened positive," but was not required to act on the
      screening results. Twenty percent of newly enrolled Medicaid health maintenance
      organization members were screened, and 2.5% were identified to have behavioral
      health and substance abuse treatment needs. As Medicaid managed care is
      responsible for the health care of low-income beneficiaries who are inherently
      vulnerable, it is important to make every effort to evaluate the impact of a
      quality project meant to improve their treatment.

PMID- 15851389
TI  - Commentary.

PMID- 15851391
TI  - Commentary: Sifting through the maze of viral and host diversity and HIV/AIDS
      clinical progression.

PMID- 15851392
TI  - Suicide risk in relation to level of urbanicity--a population-based linkage
      study.
AB  - BACKGROUND: The extent to which the high suicide rate in urban areas is
      influenced by exposures to risk factors for suicide other than urbanicity remains
      unknown. This population-based study aims to investigate suicide risk in relation
      to the level of urbanicity in the context of other factors, and to study the risk
      variation in a sex, age, and calendar year perspective. METHODS: The study is a
      nested case-control study comprising 21 169 suicides and 423 128 population
      controls matched for age and sex. Personal data on place of residence,
      socioeconomic status and psychiatric history were retrieved from various Danish
      longitudinal registers. Data were analysed with conditional logistic regression.
      RESULTS: This study confirms that people living in more urbanized areas are at a
      higher risk of suicide than their counterparts in less urbanized areas. However,
      this excess risk is largely eliminated when adjusted for personal marital,
      income, and ethnic differences; it is even reversed when further adjusted for
      psychiatric status. Moreover, the impact of urbanicity on suicide risk differs
      significantly by sex and across age. Urban living reduces suicide risk
      significantly among men, especially young men, but increases the risk among
      women, especially women aged 24-35 or >65 years. In addition, during 1981-1997,
      the suicide risk associated with urbanicity remained rather constant among women,
      whereas it dropped significantly among men, a trend that seemingly gained
      strength during the last part of this period. CONCLUSIONS: Suicide risk
      associated with urbanicity varies significantly by sex and age groups and recent
      years have seen a decline in the urban-rural disparities among men. The increased
      risk in urban areas can largely be explained by the effects of marital status,
      ethnics, income, and psychiatric status.

PMID- 15851393
TI  - Neurological status of Australian veterans of the 1991 Gulf War and the effect of
      medical and chemical exposures.
AB  - BACKGROUND: Since the 1991 Gulf War, concerns have been voiced about the effects
      on the health of veterans of Gulf War related medical and chemical exposures.
      METHODS: Our cross-sectional study compared 1424 male Australian Gulf War
      veterans and a randomly sampled military comparison group (n = 1548). A postal
      questionnaire asked about the presence of current neurological type symptoms,
      medically diagnosed neurological conditions, and medical and chemical exposures.
      A neurological examination was performed as part of a physical assessment.
      RESULTS: Veterans have a higher prevalence of neurological type symptoms (ratio
      of means 1.4, 95% confidence interval (CI) 1.2-1.5). Although the odds ratio (OR)
      of lower limb neurological type symptoms and signs in veterans compared with the
      comparison group was increased (OR = 1.6, 95% CI 1.0-2.7), it was of borderline
      significance, and there was no difference between groups according to a
      Neuropathy Score based on neurological signs alone (ratio of means 1.1, 95% CI
      0.9-1.3). The increased OR of neurological type symptoms and signs suggestive of
      a central nervous system disorder (OR = 1.8, 95% CI 1.0-3.1) was also of
      borderline significance. Veterans were not more likely to have self-reported
      medically diagnosed neurological conditions, or to have neurological type
      symptoms and signs suggestive of an anterior horn cell disorder (OR = 0.9, 95% CI
      0.5-1.6). The total number of neurological type symptoms reported by veterans,
      but not the Neuropathy Score, was associated with Gulf War related exposures
      including immunizations and pyridostigmine bromide in dose-response
      relationships, anti-biological warfare tablets, solvents, pesticides, and insect
      repellents. CONCLUSIONS: This study shows increased reporting of neurological
      type symptoms in Gulf War veterans, but no evidence for increased neurological
      effects based on objective physical signs. There may be a number of factors,
      including information bias, relating to increased neurological type symptom
      reporting in veterans.

PMID- 15851394
TI  - Commentary: Juvenile idiopathic arthritis--issues of definition and causation.

PMID- 15851395
TI  - Seasonal pattern of tuberculosis in Hong Kong.
AB  - BACKGROUND: Summer predominance of tuberculosis (TB) was reported previously in
      temperate regions. No consistent data were available for lower latitudes. METHOD:
      The monthly TB notification data in Hong Kong from 1991 to 2002 were examined for
      seasonal fluctuation. A seasonal model was then developed after standardization
      by period, sex, age, history of TB, form of disease, and bacteriological status.
      RESULTS: The raw monthly counts showed remarkably consistent seasonal fluctuation
      across different periods, sexes, and age groups. A sine model was fitted for 82
      104 notifications (adjusted R(2) = 0.373, P < 0.001). A summer peak was observed
      with seasonal fluctuation of 18.4% (P < 0.001), which was substantially higher
      than that reported previously for temperate regions. The amplitudes of
      fluctuation were 35.0, 15.0, 19.0, and 20.2% for those aged < or =14, 15-34, 35
      64, and >/=65 years, respectively (all P < 0.001). No gender difference was noted
      (18.2% vs 19.0%, P = 0.790). Seasonal pattern was detected among new cases
      (18.6%, P < 0.001), but not retreatment cases (5.2%, P = 0.333). Culture-positive
      cases showed greater fluctuation than culture-negative cases (29.4% vs 6.4%, P <
      0.001). No significant difference was found between pulmonary and extrapulmonary
      cases (16.8% vs 21.6%, P = 0.356). TB cases notified in summer were more likely
      to be smear-positive [odds ratio (OR) 1.100, 95% confidence interval (CI) 1.045
      1.158, P < 0.001] and culture-positive (OR 1.175, 95% CI 1.121-1.232, P < 0.001)
      than those notified in winter, even after stratification by other key variables.
      CONCLUSION: A consistent seasonal pattern was found, with variable amplitudes of
      fluctuation in different subgroups and differing disease characteristics in
      different seasons. These observations are suggestive of the presence of a
      seasonal disease-modifying factor.

PMID- 15851396
TI  - Correlating homicide and suicide.
AB  - BACKGROUND: The relationship between homicide and suicide has been studied
      extensively, but with conflicting results. The primary objective of this study
      was to examine the correlation between homicide and suicide rates in a large
      cross-sectional sample of UN member states. METHODS: The study used age
      standardized data on homicide and suicide for 65 international locales compiled
      by the World Health Organization. Weighted correlation coefficients between
      homicide and suicide rates were computed by sex, income level, and geographic
      region. RESULTS: The overall correlation between homicide and suicide rates was
      weak and statistically insignificant (rho = -0.08, P = 0.5178). However, when
      analysed by geographic region the data revealed two distinct patterns: homicide
      and suicide rates were positively correlated in European countries (rho = 0.89, P
      < 0.0001), but negatively correlated in the Asia Pacific Region (rho = -0.97, P <
      0.0001), and the Americas (rho = -0.62, P < 0.005). CONCLUSIONS: The strength and
      direction of the relationship between homicide and suicide vary significantly
      with geographic region. The divergent geographic patterns in the relationship
      between homicide and suicide might be due to regional differences in social and
      cultural variables.

PMID- 15851397
TI  - Differences in in vitro pollen germination and pollen tube growth of cotton
      cultivars in response to high temperature.
AB  - BACKGROUND AND AIMS: High-temperature environments with >30 degrees C during
      flowering reduce boll retention and yield in cotton. Therefore, identification of
      cotton cultivars with high-temperature tolerance would be beneficial in both
      current and future climates. * METHODS: Response to temperature (10-45 degrees C
      at 5 degrees C intervals) of pollen germination and pollen tube growth was
      quantified, and their relationship to cell membrane thermostability was studied
      in 12 cultivars. A principal component analysis was carried out to classify the
      genotypes for temperature tolerance. * KEY RESULTS: Pollen germination and pollen
      tube length of the cultivars ranged from 20 to 60 % and 411 to 903 microm,
      respectively. A modified bilinear model best described the response to
      temperature of pollen germination and pollen tube length. Cultivar variation
      existed for cardinal temperatures (T(min), T(opt) and T(max)) of pollen
      germination percentage and pollen tube growth. Mean cardinal temperatures
      calculated from the bilinear model for the 12 cultivars were 15.0, 31.8 and 43.3
      degrees C for pollen germination and 11.9, 28.6 and 42.9 degrees C for pollen
      tube length. No significant correlations were found between pollen parameters and
      leaf membrane thermostability. Cultivars were classified into four groups based
      on principal component analysis. * CONCLUSIONS: Based on principal component
      analysis, it is concluded that higher pollen germination percentages and longer
      pollen tubes under optimum conditions and with optimum temperatures above 32
      degrees C for pollen germination would indicate tolerance to high temperature.

PMID- 15851398
TI  - The relationship between acute alcohol consumption and consequent injury type.
AB  - AIMS: The aim of this study was to quantify the relationship between acute
      alcohol consumption and injury type (nature of injury, body region injured),
      while adjusting for the effect of known confounders (i.e. demographic and
      situational variables, usual drinking patterns, substance use and risk-taking
      behaviour). METHODS: A cross-sectional study was conducted between October, 2000
      and October, 2001 of patients aged >or=15 years presenting to a Queensland
      Emergency Department for treatment of an injury sustained in the preceding 24 h.
      There were three measures of acute alcohol consumption: drinking setting,
      quantity, and beverage type consumed in the 6 h prior to injury. Two variables
      were used to quantify injury type: nature of injury (fracture/dislocation,
      superficial, internal, and CNS injury) and body part injured (head/neck, facial,
      chest, abdominal, external, and extremities). Both were derived from patient
      medical records. RESULTS: Five hundred and ninety three patients were
      interviewed. Logistic regression analyses indicated that, after controlling for
      relevant confounding variables, there was no significant association between any
      of the three measures of acute alcohol consumption and injury type. CONCLUSIONS:
      The effects of acute alcohol consumption are not specific to injury type.
      Interventions aimed at reducing the incidence of alcohol-related injury should
      not be targeted at specific injury types.

PMID- 15851399
TI  - Erythrocyte thiamine (Th) esters: a major factor of the alcohol withdrawal
      syndrome or a candidate marker for alcoholism itself?
AB  - AIMS: Thiamine (Th) deficiency is a major problem in alcoholics. In this study,
      the relationship of alcohol withdrawal syndrome (AWS) to Th and its esters, as
      well as the diagnostic power of Th and its esters were investigated. PATIENTS AND
      METHODS: Th and its esters were assessed in a series of chronic alcoholics (and
      in controls) using an improved method. RESULTS: No association was found between
      AWS severity and Th and its esters, while the diagnostic power of thiamine
      diphosphate (TDP) and Th was very high. TDP was the most significant among the
      parameters under study, confirming that erythrocyte TDP is a suitable marker of
      alcoholism: TDP sensitivity across subjects was 84.1%, specificity 85.4%,
      positive predictive value 82.4%, and negative predictive value 88.0%.

PMID- 15851400
TI  - A case-control study of alcohol and substance use disorders as risk factors for
      non-fatal injury.
AB  - AIMS: While alcohol use is thought to be a major risk factor for both fatal and
      non-fatal injuries, the association of substance use disorders (alcohol use
      disorders, AUD and substance use disorders, SUD) with occurrence of injury has
      not received the same attention. To report the association of AUD and SUD,
      according to diagnostic and statistics manual of mental disorders-IV (DSM-IV) and
      international classification of diseases 10 (ICD-10) criteria, and the risk of
      non-fatal injuries. METHODS: A case-control study: Cases included 653 injured
      patients, 18-65-years-old, who attended one emergency department (ED). Controls
      included 1131 subjects from a representative sample of residents of Mexico City,
      of the same age group. Information on drug and alcohol use was obtained by
      interview using the world mental health version of the composite international
      diagnostic interview (WMH-CIDI). RESULTS: Among injured patients, the prevalence
      of substance abuse or dependence within the last 12 months was 12.3% for alcohol
      and 2.5% for other substances (marijuana, cocaine, tranquilizers, amphetamines,
      others). Among residents of Mexico City, these prevalences were 1.8 and 0.3%,
      respectively. Adjusted odds ratios (OR) of injury according to alcohol and
      substance use were 4.95 (95% confidence interval (CI): 2.87-8.52) for alcohol and
      2.58 (0.73-9.17) for other substances. An important level of comorbid alcohol and
      substance use disorders was also found. CONCLUSIONS: Efforts in the ED should be
      carried out to treat and/or refer patients with alcohol and substance use
      disorders, and special care should be taken to address comorbid cases.

PMID- 15851402
TI  - Auxin, ethylene and brassinosteroids: tripartite control of growth in the
      Arabidopsis hypocotyl.
AB  - Dark-grown Arabidopsis seedlings develop an apical hook by differential cell
      elongation and division, a process driven by cross-talk between multiple
      hormones. Auxins, ethylene and gibberellins interact in the formation of the
      apical hook. In the light, a similar complexity of hormonal regulation has been
      revealed at the level of hypocotyl elongation. Here, we describe the involvement
      of brassinosteroids (BRs) in auxin- and ethylene-controlled processes in the
      hypocotyls of both light- and dark-grown seedlings. We show that BR biosynthesis
      is necessary for the formation of an exaggerated apical hook and that either
      application of BRs or disruption of BR synthesis alters auxin response,
      presumably by affecting auxin transport, eventually resulting in the
      disappearance of the apical hook. Furthermore, we demonstrate that ethylene
      stimulated hypocotyl elongation in the light is largely controlled by the same
      mechanisms as those governing formation of the apical hook in darkness. However,
      in the light, BRs appear to compensate for the insensitivity to ethylene in hls
      mutants, supporting a downstream action of BRs. Hence, our results indicate that
      HLS1, SUR1/HLS3/RTY1/ALF1 and AMP1/HPT/COP2/HLS2/PT act on the auxin-ethylene
      interaction, rather than at the level of BRs. A model for the tripartite hormone
      interactions is presented.

PMID- 15851401
TI  - Antioxidant supplementation for the prevention of kwashiorkor in Malawian
      children: randomised, double blind, placebo controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of antioxidant supplementation in preventing
      kwashiorkor in a population of Malawian children at high risk of developing
      kwashiorkor. DESIGN: Prospective, double blind, placebo controlled trial
      randomised by household. SETTING: 8 villages in rural southern Malawi.
      PARTICIPANTS: 2372 children in 2156 households aged 1-4 years were enrolled; 2332
      completed the trial. INTERVENTION: Daily supplementation with an antioxidant
      powder containing riboflavin, vitamin E, selenium, and N-acetylcysteine in a dose
      that provided about three times the recommended dietary allowance of each
      nutrient or placebo for 20 weeks. MAIN OUTCOME MEASURES: The primary outcome was
      the incidence of oedema. Secondary outcomes were the rates of change for weight
      and length and the number of days of infectious symptoms. RESULTS: 62 children
      developed kwashiorkor (defined by the presence of oedema); 39/1184 (3.3%) were in
      the antioxidant group and 23/1188 (1.9%) were in the placebo group (relative risk
      1.70, 95% confidence interval 0.98 to 2.42). The two groups did not differ in
      rates of weight or height gain. Children who received antioxidant supplementation
      did not experience less fever, cough, or diarrhoea. CONCLUSIONS: Antioxidant
      supplementation at the dose provided did not prevent the onset of kwashiorkor.
      This finding does not support the hypothesis that depletion of vitamin E,
      selenium, cysteine, or riboflavin has a role in the development of kwashiorkor.

PMID- 15851403
TI  - In vitro activity of cyclin-dependent kinase inhibitor CYC202 (Seliciclib, R
      roscovitine) in mantle cell lymphomas.
AB  - BACKGROUND: Mantle cell lymphoma (MCL) has the worst prognosis of all B-cell
      lymphomas and has poor response to conventional therapy. It is characterized by
      the presence of a chromosomal translocation t(11:14) (q13;q32) which results in
      deregulated cyclin D1 expression. Since defects in cell cycle regulation and
      apoptosis are primary events in MCL, small-molecule inhibitors of cdks-cyclins
      may play an important role in the therapy of this disorder. CYC202 (Seliciclib, R
      roscovitine; Cyclacel Ltd., Dundee, UK) is a purine analogue and a selective
      inhibitor of the cdk2-cyclin E as well as cdk7-cyclin H and cdk9-cyclin T.
      MATERIALS AND METHODS: The activity of CYC202 was tested in four human MCL cell
      lines: REC, Granta-519, JeKo-1 and NCEB-1. The effect of CYC202 on the cell cycle
      and on apoptosis-, cell-cycle- and transcription-regulation-related proteins was
      assessed. RESULTS: The IC50 was 25 microM for REC, Granta-519 and JeKo-1 cells
      and 50 microM for NCEB-1 cells. CYC202 caused an accumulation of cells in the G2
      M phase of the cell cycle and apoptosis. CYC202 caused down-regulation of cyclin
      D1 and Mcl-1 protein levels, possibly because of the inhibition of transcription
      elongation. CONCLUSIONS: Our data suggest that CYC202 is an active agent in MCL.
      The concomitant decrease of the phosphorylated and total forms of RNA polymerase
      II suggests that this could be the main mechanism mediating the biological
      effects of CYC202 in MCL cells. The drug might represent a new therapeutic agent
      in this lymphoma subtype.

PMID- 15851404
TI  - Interleukin 1B gene (IL-1B) and interleukin 1 receptor antagonist gene (IL-1RN)
      polymorphisms in Helicobacter pylori-negative gastric cancer of intestinal and
      diffuse histotype.
AB  - BACKGROUND: Polymorphisms in the interleukin 1beta gene (IL-1B-31T/C and IL-1B
      511C/T single nucleotide changes) and in the interleukin 1 receptor anatagonist
      gene (IL-1RN2 variable number of tandem repeats) have been studied with respect
      to gastric cancer susceptibility. Available data support an aetiologic role of
      these genetic variants in the presence of concomitant Helicobacter pylori
      infection. Their contribution without H. pylori infection is still an open field
      of investigation. MATERIALS AND METHODS: IL-1B and IL-1RN polymorphisms were
      investigated in 138 H. pylori-negative Italian patients with sporadic gastric
      cancer and 100 H. pylori-negative controls. Unconditional regression with odd
      ratios (OR) and 95% confidence intervals (CI), haplotype and linkage
      disequilibrium analyses were used to investigate the association of the
      polymorphisms with disease. RESULTS: In all gastric cancer cases, carriers of the
      homozygous IL-1B-511T/T genotype showed a significant risk for the development of
      the disease (OR 3.2 with 95% CI 1.27-8.05). In cases with intestinal-type gastric
      cancer, however, both IL-1B-511T and IL-1RN2 alleles were associated with
      disease. In this subgroup, the odds ratio for carriers of both IL-1B-511T and IL
      1RN2 was 6.49 (95% CI 2.07-20.4). Haplotype analysis supported the aetiologic
      contribution of these alleles in gastric cancer of the intestinal histotype.
      CONCLUSIONS: In conclusion, IL-1B-511T and IL-1RN2 may contribute to intestinal
      gastric cancer risk in the absence of concomitant H. pylori infection. In this
      setting, future epidemiologic studies should consider dietary habits and exposure
      to carcinogens interacting with pro-inflammatory host genotypes.

PMID- 15851405
TI  - Akt activation in renal cell carcinoma: contribution of a decreased PTEN
      expression and the induction of apoptosis by an Akt inhibitor.
AB  - BACKGROUND: Akt has been implicated in the oncogenesis of human malignant tumors,
      because Akt regulates many key effector molecules involved in cell survival. PTEN
      (phosphatase and tensin homolog deleted on chromosome 10) negatively regulates
      Akt activation. MATERIALS AND METHODS: The expression of phosphorylated Akt (p
      Akt), total Akt and PTEN was analyzed by Western blotting in 45 renal cell
      carcinoma (RCC) patients. The Bad and phosphorylated Bad (p-Bad) statuses were
      analyzed in 20 RCC patients. A phosphatidylinositol ether analog was used as an
      Akt inhibitor to treat four RCC cell lines, namely Caki-1, KU19-20, SW839 and
      Caki-2. RESULTS: The PTEN expression in RCC was observed to decrease and p-Akt
      expression to increase significantly in comparison with that in the corresponding
      normal kidney tissue. The PTEN expression inversely correlated with the p-Akt
      expression. These alterations were specific for clear cell type RCC, but not for
      papillary or chromophobe type RCC. Alterations in Bad phosphorylation were also
      specifically observed in clear cell type. The Akt inhibitor induced apoptosis in
      KU19-20 and Caki-2 cells with a high Akt activity. CONCLUSIONS: A decreased
      expression of PTEN may be an underlying mechanism for Akt activation. An Akt
      inhibitor may be a therapeutic option for a subset of RCC with an elevated Akt
      activity.

PMID- 15851406
TI  - Epidermal growth factor receptor activating mutations in Spanish gefitinib
      treated non-small-cell lung cancer patients.
AB  - BACKGROUND: North American and Japanese non-small-cell lung cancer (NSCLC)
      patients with epidermal growth factor receptor (EGFR) activation via tyrosine
      kinase (TK) mutations respond dramatically to gefitinib treatment. To date,
      however, the frequency and effect of EGFR TK mutations have not been examined in
      European patients. PATIENTS AND METHODS: Eighty-three Spanish advanced NSCLC
      patients who had progressed after chemotherapy, were treated with compassionate
      use of gefitinib. Patients were selected on the basis of available tumor tissue.
      Tumor genomic DNA was retrieved from paraffin-embedded tissue obtained by laser
      capture microdissection. EGFR mutations in exons 19 and 21 were examined by
      direct sequencing. RESULTS: EGFR mutations were found in 10 of 83 (12%) of
      patients. All mutations were found in adenocarcinomas, more frequently in females
      (P=0.007) and non-smokers (P=0.01). Response was observed in 60% of patients with
      mutations and 8.8% of patients with wild-type EGFR (P=0.001). Time to progression
      for patients with mutations was 12.3 months, compared with 3.6 months for
      patients with wild-type EGFR (P=0.002). Median survival was 13 months for
      patients with mutations and 4.9 months for those with wild-type EGFR (P=0.02).
      CONCLUSIONS: EGFR TK mutational analysis is a novel predictive test for selecting
      lung adenocarcinoma patients for targeted therapy with EGFR TK inhibitors.

PMID- 15851407
TI  - SOR guidelines for concomitant chemoradiotherapy for patients with uterine
      cervical cancers: evidence update bulletin 2004.
AB  - BACKGROUND: In 1993 the French National Federation of Cancer Centres (FNCLCC)
      initiated the Standards, Options and Recommendations (SOR) project. This is a
      collaboration between the FNCLCC, the 20 French cancer centres, and specialists
      from French public universities, general hospitals and private clinics, and some
      specialists learned societies. The main objective is to develop clinical practice
      guidelines to improve the quality of health care and the outcome of cancer
      patients. MATERIALS AND METHODS: The SORs are developed using a methodology based
      on a literature review and critical appraisal by a multidisciplinary group of
      experts, with feedback from specialists in cancer care delivery. RESULTS: In
      1999, the initial SORs for the management of women with cervical cancer were
      published. At that time the use of chemoradiotherapy was considered as an option.
      Since this original publication, five randomised trials comparing
      chemoradiotherapy with radiotherapy have been published, as well as a systematic
      review and two other clinical practice guidelines. In the light of this
      additional evidence, it was decided to update the guidelines on chemoradiotherapy
      in women with cervical cancer. CONCLUSION: After selection, critical analysis and
      integration of new evidence, chemoradiotherapy has become a standard for women
      with cervical cancer.

PMID- 15851408
TI  - CAG repeat polymorphism in the DNA polymerase gamma gene in a Polish population:
      an association with testicular cancer risk.

PMID- 15851409
TI  - SV40 infection in human cancers.

PMID- 15851410
TI  - Subjective assessments of safety, exposure to chemicals and use of personal
      protection equipment in seafaring.
AB  - BACKGROUND: Most of the scientific publications from the maritime area are
      studies about the mortality and morbidity, while studies about the present
      hazards of potentially dangerous exposures are relatively rare. AIMS: To describe
      the seafarers' assessments of the occupational safety on board, their exposure to
      chemicals and the use of personal protection equipment and to identify the areas
      for further risk assessment and preventive measures. METHODS: A questionnaire
      study was carried out in 11 countries among seafarers who attended a regular
      health examination. RESULTS: The total number of seafarers who participated in
      the study was 6461 (response rate 93.7%). The occupational safety on board was
      assessed to be very good or good in 82%. Multivariate analyses showed that the
      safety was assessed as lowest among ratings, seafarers<30 years of age, work in
      the engine rooms and on dry cargo ships. It was highest on crude oil tankers and
      supply ships. Fifty-five per cent of seafarers were exposed to chemicals.
      Personal protection equipment to chemicals was used 'always/almost always' in 93%
      of the exposed. Multivariate analysis showed that the use of personal protection
      was highest on deck, on the largest ships, on roll-on roll-off ships and on crude
      oil tankers. CONCLUSION: The occupational safety and the use of personal
      protective equipment was assessed to be significantly different in some strata of
      the population and in specific working areas and types and sizes of ships.

PMID- 15851411
TI  - Strategies to maintain redox homeostasis during photosynthesis under changing
      conditions.
AB  - Plants perform photosynthesis and assimilatory processes in a continuously
      changing environment. Energy production in the various cell compartments and
      energy consumption in endergonic processes have to be well adjusted to the
      varying conditions. In addition, dissipatory pathways are required to avoid any
      detrimental effects caused by over-reduction. A large number of short-term and
      long-term mechanisms interact with each other in a flexible way, depending on
      intensity and the type of impact. Therefore, all levels of regulation are
      involved, starting from energy absorption and electron flow events through to
      post-transcriptional control. The simultaneous presence of strong oxidants and
      strong reductants during oxygenic photosynthesis is the basis for regulation.
      However, redox-dependent control also interacts with other signal transduction
      pathways in order to adapt metabolic processes and redox-control to the
      developmental state. Examples are given here for short-term and long-term control
      following changes of light intensity and photoperiod, focusing on the dynamic
      nature of the plant regulatory systems. An integrating network of all these
      mechanisms exists at all levels of control. Cellular homeostasis will be
      maintained as long as the mechanisms for acclimation are present in sufficiently
      high capacities. If an impact is too rapid, and acclimation on the level of gene
      expression cannot occur, cellular damage and cell death are initiated.

PMID- 15851412
TI  - Thioredoxin affinity chromatography: a useful method for further understanding
      the thioredoxin network.
AB  - Thioredoxin affinity chromatography can be used to recognize the target proteins
      of thioredoxin or thioredoxin-related proteins in whole cells or certain cellular
      compartments. In the last couple of years, many potential target proteins have
      been identified from various organelles and organisms by this method. Based on
      the information on the target proteins provided by these studies, the complete
      thioredoxin-related redox networks can now be efficiently described.

PMID- 15851413
TI  - P-deficiency increases the O2 uptake per N2 reduced in alfalfa.
AB  - Nodulated alfalfa (Medicago sativa L. cv. Saranac) plants were grown in
      hydroponics at P-sufficient and P-deficient supply levels. After 5 weeks of
      growth, dry matter accumulation, nodulation, total N and P accumulation, as well
      as 15N2 uptake, were measured. Moreover, the response of nodule O2-uptake to
      raising external pO2 was determined in an open-flow measurement system and nodule
      permeability was calculated. Plants in the P-deficient supply treatment had a
      lower P concentration in all organs. In both treatments the highest P
      concentration was found in nodules. In the P-deficient supply treatment plants
      formed less dry matter, had a lower shoot/root ratio, less nodulation, decreased
      total N accumulation, and lower 15N2 uptake per dry matter nodule. Nodules in the
      P-deficient treatment were, on average, smaller and had a higher O2 uptake per N2
      reduced, coinciding with increased nodule permeability and conductance. Thus
      increased oxygen uptake appears to be a mechanism to adjust nodule metabolism to
      P deficiency in indeterminate N2-fixing nodules such as in alfalfa, as has
      previously been shown for determinate nodule forms.

PMID- 15851414
TI  - Characterization of the ethanol-inducible alc gene expression system in tomato.
AB  - The efficacy of the ethanol-inducible alc transgene expression system, derived
      from the filamentous fungus Aspergillus nidulans, has been demonstrated in
      transgenic tomato. Two direct comparisons have been made. First, this study has
      utilized two transgenic lines carrying distinct reporter genes (chloramphenicol
      acetyltransferase and beta-glucuronidase) to distinguish aspects of induction
      determined by the nature of the gene/gene product rather than that of the plant.
      Second, comparisons have been made to data generated in other species in order to
      identify any species-specific effects. The induction profiles for different genes
      in different species have shown remarkable similarity indicating the broad
      applicability of this gene switch. While there are minor differences observed
      between species, these probably arise from diversity in their metabolism. A
      series of potential alternative inducers have also been tested, revealing that
      ethanol (through metabolism to acetaldehyde) is better than other alcohols and
      ketones included in this study. Expression driven by alc was demonstrated to vary
      spatially, the upper younger leaves having higher activity than the lower older
      leaves; this will be important for some applications, and for experimental
      design. The highest levels of activity from ethanol-inducible transgene
      expression were determined to be the equivalent of those from the constitutive
      Cauliflower Mosaic Virus 35S promoter. This suggests that the alc system could be
      an important tool for plant functional genomics.

PMID- 15851415
TI  - Redox regulation in the chloroplast thylakoid lumen: a new frontier in
      photosynthesis research.
AB  - Initially linked to photosynthesis, regulation by change in the redox state of
      thiol groups (S-S<-- -->2SH) is now known to occur throughout biology. Thus, in
      addition to serving important structural and catalytic functions, it is
      recognized that, in many cases, disulphide bonds can be broken and reformed for
      regulation. Several systems, each linking a hydrogen donor to an intermediary
      disulphide protein, act to effect changes that alter the activity of target
      proteins by change in the thiol redox state. Pertinent to the present discussion
      is the chloroplast ferredoxin/thioredoxin system, comprised of photoreduced
      ferredoxin, a thioredoxin, and the enzyme ferredoxin-thioredoxin reductase, that
      occur in the stroma. In this system, thioredoxin links the activity of enzymes to
      light: those enzymes functional in biosynthesis are reductively activated by
      light via thioredoxin (S-S-->2SH), whereas counterparts acting in degradation are
      deactivated under illumination conditions and are oxidatively activated in the
      dark (2SH-->S-S). Recent research has uncovered a new paradigm in which an
      immunophilin, FKBP13, and potentially other enzymes of the chloroplast thylakoid
      lumen are oxidatively activated in the light (2SH-->S-S). The present review
      provides a perspective on this recent work.

PMID- 15851416
TI  - Altered photosynthetic performance of a natural Arabidopsis accession is
      associated with atrazine resistance.
AB  - Natural variation for photosynthetic traits was studied by determining
      chlorophyll fluorescence parameters in a collection of Arabidopsis accessions.
      This screen revealed only one single accession (Ely), exhibiting photosynthetic
      characteristics markedly different from all others, while a few lines showed
      small but significant variation. Detailed genetic and physiological analyses
      showed reduced fitness for Ely compared with the standard laboratory strain Ler
      for various growth parameters. At low temperature (15 degrees C), Ely had a
      higher electron transport rate than Ler, indicating increased photosystem II
      efficiency under this condition, while at high temperature (30 degrees C) the
      opposite was observed. Ely had a high sensitivity to UV-B radiation compared with
      Ler and was atrazine resistant. This atrazine-resistance and related chlorophyll
      fluorescence traits were maternally inherited, pointing towards chloroplast
      located gene(s). Definite proof that Ely is atrazine-resistant was obtained by
      sequencing the psbA gene, encoding the D1 protein of photosystem II, revealing a
      point mutation causing the same amino acid change as found in other atrazine
      resistant species. Additional nuclear encoded genetic variation was also present,
      as was concluded from the small but significant differences in phenotype between
      Ely and its reciprocal crosses with Ler. It was concluded that the photosynthetic
      yield is highly conserved and that only severe selection pressure results in
      marked variations in photosynthetic performance.

PMID- 15851417
TI  - Comparison of changes in fruit gene expression in tomato introgression lines
      provides evidence of genome-wide transcriptional changes and reveals links to
      mapped QTLs and described traits.
AB  - Total soluble solids content is a key determinant of tomato fruit quality for
      processing. Several tomato lines carrying defined introgressions from S.
      pennellii in a S. lycopersicum background produce fruit with elevated Brix, a
      refractive index measure of soluble solids. The genetic basis for this trait can
      be determined by fine-mapping each QTL to a single gene, but this is time
      consuming and technically demanding. As an alternative, high-throughput
      analytical technologies can be used to provide useful information that helps
      characterize molecular changes in the introgression lines. This paper presents a
      study of transcriptomic changes in six introgression lines with increased fruit
      Brix. Each line also showed altered patterns of fruit carbohydrate accumulation.
      Transcriptomic changes in fruit at 20 d after anthesis (DAA) were assessed using
      a 12 000-element EST microarray and significant changes analysed by SAM
      (significance analysis of microarrays). Each non-overlapping introgression
      resulted in a unique set of transcriptomic changes with 78% of significant
      changes being unique to a single line. Principal components analysis allowed a
      clear separation of the six lines, but also revealed evidence of common changes;
      lines with quantitatively similar increases in Brix clustered together. A
      detailed examination of genes encoding enzymes of primary carbon metabolism
      demonstrated that few of the known introgressed alleles were altered in
      expression at the 20 DAA time point. However, the expression of other metabolic
      genes did change. Particularly striking was the co-ordinated up-regulation of
      enzymes of sucrose mobilization and respiration that occurred only in the two
      lines with the highest Brix increase. These common downstream changes suggest a
      similar mechanism is responsible for large Brix increases.

PMID- 15851418
TI  - Can we abolish skull x rays for head injury?
AB  - OBJECTIVES: To assess the effect of a change in skull x ray policy on the rate of
      admission, use of computed tomography (CT), radiation dose per head injury, and
      detection of intracranial injuries; and to compare the characteristics of
      patients with normal and abnormal head CT. DESIGN: Retrospective cohort study.
      SETTING: UK paediatric teaching hospital emergency department. PATIENTS: 1535
      patients aged between 1 and 14 years with a head injury presenting to the
      emergency department between 1 August 1998 and 31 July 1999 (control period), and
      1867 presenting between 1 August 2002 and 31 July 2003 (first year of new skull x
      ray policy). INTERVENTION: Hospital notes and computer systems were analysed and
      data were collected on all patients presenting with a head injury. RESULTS: The
      abolition of skull x rays in children aged over 1 year prevented about 400 normal
      skull x rays being undertaken in period 2. The percentage of children undergoing
      CT rose from 1.0% to 2.1% with no change in the positive CT pick up rate (25.6% v
      25.0%). There was no significant change in admission rate (10.9% v 10.1%), and a
      slight decrease in the radiation dose per head injury (0.042 mSv compared to
      0.045 mSv). CONCLUSIONS: Skull x rays can be abandoned in children aged 1 to 14
      without a significant increase in admission rate, radiation dose per head injury,
      or missed intracranial injury. The mechanism and history of the injury and a
      reduced Glasgow coma scale are probably the most important indicators of
      significant head injury in children.

PMID- 15851419
TI  - Pyridoxine or pyridoxal phosphate for intractable seizures?

PMID- 15851420
TI  - Academic paediatrics: Easter Island or Easter Sunday?

PMID- 15851421
TI  - Success in tackling deafness with multi-faceted interventions.

PMID- 15851422
TI  - Is there a relation between SIDS and long QT syndrome?

PMID- 15851423
TI  - A survey of clinical academic staffing in paediatrics and child health in the UK.
AB  - BACKGROUND: The state of academic paediatrics in the United Kingdom is a source
      of anxiety in view of anecdotal reports of loss of identity within medical
      schools and reductions in staffing levels. AIMS: To measure the current numbers
      and recent changes in clinical academic staff in all university departments of
      paediatrics in the UK. METHODS: A questionnaire was sent to all 24 university
      departments of paediatrics where undergraduates are taught, and to the
      postgraduate institute of paediatrics. RESULTS: Full responses were obtained from
      24 medical institutions. In the past five years there has been an overall 7.2%
      decline in clinical academic staff, but among lecturers there has been a 26%
      reduction. Nine of 24 departments had undergone changes in name with at least
      some loss of paediatric identity. In 12 of 24 centres it was felt that the
      research assessment exercise had resulted in some, or severe, detriment.
      CONCLUSIONS: This study confirms the recent loss of academic training positions,
      leading to a serious concern about the future of academic paediatrics in some UK
      centres.

PMID- 15851424
TI  - Families affected by deafness: hospital services uptake in a multiethnic
      population.
AB  - AIMS: To examine the uptake of relevant hospital services by families with deaf
      children and to compare use of these services between Pakistani and white
      families. METHODS: A total of 214 deaf children with amplification aids who
      attended their paediatric outpatient and school medical appointments from October
      2000 to March 2003 were studied in an observational cohort study. RESULTS: The
      demographic profile of both the Pakistani and white families was similar.
      Pakistani children had a statistically significant excess of the following risk
      factors: consanguineous marriages (86.4% Pakistani, 1.5% white), family history
      of deafness (66.4% Pakistani, 38.8% white), and family size (birth order >5:
      12.8% Pakistani: 4.5% white). White children were more likely to have had post
      meningitis deafness (1.4% Pakistani, 13.4% white) and congenital infections, or
      have dysmorphic features (5.0% Pakistani, 13.4% white). Overall the uptake of
      relevant hospital services by Pakistani and white families was very similar
      irrespective of an early or late diagnosis. There was an increased likelihood of
      white families declining cochlear implantation (17.6% Pakistani, 75.0% white).
      CONCLUSIONS: This study did not show significant differences in hospital service
      uptake despite different risk profiles for childhood deafness for both Pakistani
      and white families in Bradford. Among specialist services offered, cochlear
      implantation was more likely to be accessed by Pakistani families.

PMID- 15851426
TI  - Monitoring trends in obesity in South Wales using routine data.
AB  - AIM: To use existing data on height and weight of 5 year old children, routinely
      recorded annually as part of the school entry medical, to monitor trends in
      obesity over the last 16 years in three South Wales localities. METHODS: Body
      mass index (BMI) and percentage of children over the cut off points for being
      overweight or obese proposed by the International Obesity Task Force were
      determined in 46,073 children who had height, weight, and sex recorded each
      school year (between 1986/87 and 2001/02) on the National Child Health Computer
      System held at the Swansea NHS Trust. RESULTS: With the exception of one year,
      the coverage for BMI measurements ranged between 87% and 99%. The accuracy of
      measurement and data entry was identified as suspect in some cases, and although
      some data entry errors could be corrected, 14% of BMI measurements were
      inadmissible. Logistic regression analysis of BMI trends in the remainder showed
      that the percentage of 5 year olds classified as overweight or obese had
      increased significantly over the time period and that the rate of change in girls
      was significantly greater than that in boys. CONCLUSION: Overweight and obese
      children have increased in frequency in this population. The Child Health
      Computer System is potentially a valuable source of information on the health
      status of populations and should be capable of monitoring trends in obesity.
      However, accuracy of measurement and data entry need to be improved, and the
      system, to be useful on a national basis, needs to be amalgamated at a higher
      level than individual NHS Trusts.

PMID- 15851425
TI  - Effect of Gaviscon Infant on gastro-oesophageal reflux in infants assessed by
      combined intraluminal impedance/pH.
AB  - BACKGROUND: Gaviscon Infant (GI) has been recommended for gastro-oesophageal
      reflux (GOR) in infants. Its efficacy has not been examined with a
      physiologically appropriate denominator to define the degree of GOR. AIM: To
      investigate the influence of Gaviscon Infant on GOR in infants using combined pH
      and intraluminal impedance measurement. METHODS: Twenty infants (mean age 163.5
      days, range 34-319 days) exclusively bottle fed, with symptoms clinically
      suggestive of GOR, underwent 24 hour studies of intra-oesophageal 6 channel
      impedance and dual channel pH monitoring, during which six random administrations
      (3+3) of Gaviscon Infant (625 mg in 225 ml milk) or placebo (mannitol and Solvito
      N, 625 mg in 225 ml milk) were given in a double blind fashion. Impedance/pH
      reflux data were recorded and analysed blind by one observer. RESULTS: The median
      number of reflux events/hour (1.58 v 1.68), acid reflux events/hour (0.26 v
      0.43), minimum distal or proximal pH, total acid clearance time per hour (time
      with pH below pH 4), and total reflux duration per hour were not significantly
      different after GI than after placebo. Reflux height was marginally lower after
      GI (median 66.6% v 77.3% oesophageal length) compared with placebo. CONCLUSIONS:
      Results showed a marginal but significant difference between Gaviscon Infant and
      placebo in average reflux height, and raises questions regarding any perceived
      clinical benefit of its use.

PMID- 15851427
TI  - Diabetes care provision and glycaemic control in Northern Ireland: a UK regional
      audit.
AB  - AIMS: To assess the care received, compared to national guidelines, and to
      investigate factors associated with glycaemic control in children and adolescents
      with type 1 diabetes attending clinics in Northern Ireland. METHODS: An audit of
      the care provided to all patients attending 11 paediatric diabetes clinics
      commenced in 2002. A research nurse interviewed 914 patients completing a
      questionnaire recording characteristics, social circumstances, and aspects of
      diabetes management, including the monitoring of complications and access to
      members of the diabetes team. Glycaemic control was measured by glycosylated
      haemoglobin (HbA1c), determined at a DCCT aligned central laboratory. RESULTS:
      The average HbA1c concentration was 8.8% (SD 1.5%), with 20% of patients
      achieving recommended HbA1c levels of less than 7.5%. In the year prior to the
      audit, 76% of patients were reviewed by a diabetes specialist nurse and 42% were
      tested for microalbuminuria. After adjustment for confounding factors, better
      glycaemic control was identified, particularly in patients who had attended
      exactly four diabetes clinics in the previous year, were members of the patient
      association Diabetes UK, and lived with both natural parents. CONCLUSIONS: In
      Northern Ireland only a minority of patients achieved recommended HbA1c levels.
      Furthermore, children and adolescents with diabetes were reviewed by fewer
      specialists and were less intensively monitored for microvascular complications
      than recommended. There was evidence of better control in children who were
      members of Diabetes UK, suggesting that parental attitude and involvement could
      lead to benefits.

PMID- 15851428
TI  - Case gender and severity in cerebral palsy varies with intrauterine growth.
AB  - BACKGROUND: There is an unexplained excess of cerebral palsy among male babies.
      There is also variation in the proportion of more severe cases by birth weight.
      It has recently been shown that the rate of cerebral palsy increases as
      intrauterine size deviates up or down from an optimum about one standard
      deviation heavier than population mean weight-for-gestation. AIMS: To determine
      whether the gender ratio or the severity of cases also varies with intrauterine
      size. METHODS: A total of 3454 cases of cerebral palsy among single births
      between 1976 and 1990 with sufficient data to assign case severity (based on
      intellectual impairment and walking ability) and to compare weight-for-gestation
      at birth to sex specific fetal growth standards, were aggregated from nine
      separate registers in five European countries. RESULTS: The greater the degree to
      which growth deviates either up or down from optimal weight-for-gestation at
      birth, the higher is the rate of cerebral palsy, the larger is the proportion of
      male cases, and the more severe is the functional disability. Compared to those
      with optimum growth the risk of more severe cerebral palsy in male babies is 16
      times higher for those with a birth weight below the 3rd centile and four times
      higher when birth weight is above the 97th centile. In contrast, for mild
      cerebral palsy in female babies the excess risks at these growth extremes are
      about half these magnitudes. CONCLUSIONS: Among singleton children with cerebral
      palsy, abnormal intrauterine size, either small or large, is associated with more
      severe disability and male sex.

PMID- 15851429
TI  - Grommets in otitis media with effusion: an individual patient data meta-analysis.
AB  - AIMS: To identify subgroups of children with otitis media with effusion (OME)
      that might benefit more than others from treatment with ventilation tubes.
      METHODS: An individual patient data (IPD) meta-analysis on seven randomised
      controlled trials (n = 1234 children in all), focusing on interactions between
      treatment and baseline characteristics--hearing level (HL), history of acute
      otitis media, common colds, attending day-care, gender, age, socioeconomic
      status, siblings, season, passive smoking, and history of breast feeding. Outcome
      measures that could be studied were mean time spent with effusion (n = 557), mean
      hearing levels (n = 557 in studies that randomised children, and n = 180 in
      studies that randomised ears), and language development (n = 381). RESULTS: In
      the trials that treated both ears the only significant interaction was between
      day-care and surgery, occurring where mean hearing level was the outcome measure.
      None of the other baseline variables showed an interaction effect with treatment
      that would justify subgrouping. In the trials that treated only one ear, the
      baseline hearing level showed a significant but not pervasive interaction with
      treatment-that is, only with a cut-off of 25 dB HL. CONCLUSIONS: The effects of
      conventional ventilation tubes in children studied so far are small and limited
      in duration. Observation (watchful waiting) therefore seems to be an adequate
      management strategy for most children with OME. Ventilation tubes might be used
      in young children that grow up in an environment with a high infection load (for
      example, children attending day-care), or in older children with a hearing level
      of 25 dB HL or greater in both ears persisting for at least 12 weeks.

PMID- 15851430
TI  - Quality of life in chronic illness: perceptions of parents and paediatricians.
AB  - AIMS: To investigate the differences in perception of quality of life between
      parents of chronically ill children and paediatricians at diagnosis and follow
      up. Quality of life was assessed using the (HUI3). METHODS: Longitudinal study
      (July 1999-January 2002) of 37 paediatricians and 181 parents of patients
      (children aged 1-17 years) with cystic fibrosis admitted for a pneumonia or
      patients with newly diagnosed acute lymphatic leukaemia, juvenile idiopathic
      arthritis, or asthma. Main outcome measure was percentage agreement on the
      attributes of the HUI3 between parents and paediatricians. RESULTS: Differences
      in perception of health and wellbeing between paediatricians and parents of
      children with a chronic disease were found, not only at diagnosis but also after
      a period of follow up. Differences were particularly clear in the subjective
      attributes emotion (range of agreement 28-68%) and pain/discomfort (range of
      agreement 11-33%). In all patient groups, at baseline and follow up, the
      paediatrician assessed the patient to have less pain/discomfort in comparison to
      the parents. Despite a prolonged patient- paediatrician relationship, differences
      at follow up did not decrease compared to baseline. CONCLUSION: At the onset of a
      chronic disease, but also after a period of follow up, quality of life of
      paediatric patients may be misunderstood by healthcare professionals, especially
      in the subjective attributes. Systematic assessment of quality of life may
      contribute to better understanding between physicians and parents.

PMID- 15851431
TI  - Maternal diet in pregnancy and offspring blood pressure.
AB  - Associations between maternal nutrient intakes in late pregnancy and offspring
      blood pressure at 7(1/2) years were investigated in 6944 singletons from the Avon
      Longitudinal Study of Parents and Children. The only finding was a weak inverse
      association with omega-3 fatty acids that was lost after adjustment for potential
      confounders, suggesting that diet in pregnancy does not influence offspring blood
      pressure in well-nourished populations.

PMID- 15851432
TI  - Bisphosphonate treatment of bone disease.
AB  - In 1997 a review article on bisphosphonates in this journal identified 24
      published articles relating to children at that time. Since then there has been a
      considerable increase in their use in clinical paediatric practice and research
      with there being nearly a further one hundred articles published at the time of
      writing.

PMID- 15851433
TI  - Adverse psychological effects of corticosteroids in children and adolescents.
AB  - Children and adolescents treated with oral, inhaled, and intravenous
      corticosteroids (CS) may experience adverse psychological side effects (APSE),
      including psychotic symptoms. These can occur at any point during treatment,
      including withdrawal. In this paper the literature on these effects in children
      and adults is reviewed. From the evidence available, it is not possible to give
      reliable estimates for incidence or prevalence of APSE, nor clear risk factors.
      Some evidence is reported to suggest that oral dexamethasone treatment may carry
      a higher risk of APSE than other CS, but this requires further investigation.
      There is evidence from the adult literature that higher CS doses increase the
      risk of APSE. However, the dose response effect is not straightforward or
      predictable for individuals or groups. This is likely to be a reflection of the
      complex effects of CS on the central nervous system and the probable interplay
      between individual susceptibility, disease factors, and external environmental
      stressors in the emergence of APSE. More research is required to further our
      understanding of the adverse effects of these clinically valuable agents.

PMID- 15851434
TI  - Tracing Sydenham's chorea: historical documents from a British paediatric
      hospital.
AB  - Sydenham's chorea (SC) became a well defined nosological entity only during the
      second half of the nineteenth century. Such progress was promoted by the
      availability of large clinical series provided by newly founded paediatric
      hospitals. This paper analyses the demographic and clinical features of patients
      with chorea admitted to the first British paediatric hospital (the Hospital for
      Sick Children, Great Ormond Street, London) between 1852 and 1936. The seasonal
      and demographic characteristics of SC during this time appear strikingly similar
      to those observed today, and witness the introduction of modern "statistically
      averaging" techniques in the approach to complex paediatric syndromes. Great
      Ormond Street (GOS) hospital case notes provide detailed descriptions of the
      "typical cases" of SC, and show that British physicians working in the early age
      of paediatric hospitals succeeded in recognising the most distinctive clinical
      features of this fascinating condition.

PMID- 15851435
TI  - Pyridoxal phosphate is better than pyridoxine for controlling idiopathic
      intractable epilepsy.
AB  - AIM: To study the difference between pyridoxine (PN) and its active form,
      pyridoxal phosphate, (PLP) in control of idiopathic intractable epilepsy in
      children. METHODS: Among 574 children with active epilepsy, 94 (aged 8 months to
      15 years) were diagnosed with idiopathic intractable epilepsy for more than six
      months. All received intravenous PLP 10 mg/kg, then 10 mg/kg/day in four divided
      doses. If seizures recurred within 24 hours, another dose of 40 mg/kg was given,
      followed by 50 mg/kg/day in four divided doses. For those patients whose seizures
      were totally controlled, PLP was replaced by the same dose of oral PN. If the
      seizure recurred, intravenous PLP was infused followed by oral PLP 50 mg/kg/day.
      RESULTS: Fifty seven patients had generalised seizures (of whom 13 had infantile
      spasms) and 37 had focal seizure. Eleven had dramatic and sustained responses to
      PLP; of these, five also responded to PN. Within six months of treatment with PLP
      or PN, five of the 11 patients were seizure free and had their previous
      antiepileptic medicine tapered off gradually. Two were controlled with pyridoxine
      and the other three needed PLP to maintain seizure freedom. The remaining six
      responders needed PLP exclusively for seizure control. Six of the 11 responders
      to PLP had infantile spasms (46%); four of them needed PLP exclusively. The other
      five responders were in the remaining 81 patients with other seizure type.
      CONCLUSIONS: PLP could replace PN in the treatment of intractable childhood
      epilepsy, particularly in the treatment of infantile spasms.

PMID- 15851436
TI  - Prevalence of respiratory symptoms in under 5s: 1993 to 2001.
AB  - AIM: To describe changes in the prevalence of respiratory symptoms in 1-4 year
      olds in two general practice populations observed on four occasions over an eight
      year period. METHODS: In 1993, 1995, 1999, and 2001, questionnaires were posted
      to the parents of patients aged 15 years or younger and registered with either of
      two general practices. Only children aged 1-4 years at time of questionnaire
      completion were included in this study. For each survey, the prevalence of five
      key variables was determined. RESULTS: The response rates for all children in the
      four surveys were 72.8%, 70.6%, 65.0%, and 60.7% respectively. When respondents
      aged 1-4 years old were stratified into one-year age bands, there was a decrease
      in the prevalence of symptoms over the study period. This was statistically
      significant for wheeze and night cough in 2 year olds and for night cough in 4
      year olds. Repeated antibiotic prescriptions decreased significantly for 2 and 3
      year olds. There were no changes in the prevalence of hay fever or eczema and
      family history of asthma. CONCLUSIONS: The downward trend in symptom prevalence
      might represent a real decrease in symptoms or improvements in treatment. In the
      absence of changes in the prevalence of hay fever and family history of asthma,
      the downward trend in symptom prevalence may suggest changes in the prevalence of
      conditions other than asthma.

PMID- 15851437
TI  - Infection, health problems, and health care utilisation, and the risk of sudden
      infant death syndrome.
AB  - AIM: To examine whether symptoms suggestive of infection, health problems, and
      health care utilisation are risk factors for SIDS. METHODS: Matched case-control
      study with 333 SIDS infants and 998 control infants matched for region, age,
      gender, and reference sleep. Information was obtained by parental interview,
      paediatrician completed questionnaire, and hospital admission data. RESULTS: No
      symptoms were associated with SIDS after adjustment for potential confounders.
      Illness in the last four weeks as reported by the paediatrician did not differ
      between cases and controls. Developmental problems and special investigations at
      any stage of life significantly increased the risk of SIDS (adjusted OR = 2.14
      and 2.07). Admission to hospital after the first week of life was associated with
      an increased risk of SIDS (adjusted OR = 1.88). CONCLUSION: Symptoms of infection
      and illness are no longer risk factors for SIDS in communities such as Germany
      where few infants sleep prone. The increased risk of SIDS with developmental
      problems may indicate that infants which subsequently die of SIDS are abnormal or
      in some way vulnerable.

PMID- 15851438
TI  - Prospective study of community needlestick injuries.
AB  - Fifty three children were referred following community needlestick injuries,
      August 1995 to September 2003. Twenty five attended for serology six months
      later. None were positive for HIV, or hepatitis B or C. Routine follow up after
      community needlestick injury is unnecessary. HIV post-exposure prophylaxis should
      only be considered in high risk children.

PMID- 15851439
TI  - Long term sport involvement and sport injury rate in elite young athletes.

PMID- 15851440
TI  - Near-miss SIDS due to Brugada syndrome.
AB  - A 19 day old infant was successfully resuscitated from ventricular fibrillation.
      The 12 lead ECG was normal, with a normal QT interval, and remains so over three
      years follow up. DNA analysis revealed a missense mutation (R1193Q) in the SCN5A
      gene, previously linked with familial sudden unexpected nocturnal death syndrome,
      also known as Brugada syndrome.

PMID- 15851441
TI  - Old world cutaneous leishmaniasis infection in children: a case series.

PMID- 15851442
TI  - Successful tacrolimus (FK506) therapy in a child with pyoderma gangrenosum.

PMID- 15851443
TI  - Influenza burden of illness, diagnosis, treatment, and prevention: what is the
      evidence in children and where are the gaps?
AB  - Influenza is a disease of global public health significance. Traditionally the
      emphasis has been on adult disease because of the impact of influenza related
      mortality in the elderly and other high risk groups. However, it is becoming
      increasingly better recognised that young children suffer considerable morbidity
      from influenza. There are also potential consequences for siblings, parents,
      other carers, and extended family members in terms of secondary infections and
      carer leave. Influenza infection in childhood could be effectively prevented
      through vaccination. However, the United States is the only industrialised
      country currently recommending universal influenza vaccination for young children
      (between the ages of 6 and 23 months), as opposed to vaccinating only those with
      high risk conditions.

PMID- 15851444
TI  - Minimally invasive surgery.
AB  - In 1987 Mouret performed the first laparoscopic cholecystectomy, starting a
      revolution in surgery. For paediatricians it is difficult to appreciate the
      magnitude of what has occurred in this short period. The development of minimal
      access techniques represents the most significant change in surgical practice
      since the introduction of aseptic technique or safe anaesthesia. As with many
      innovations, rapid change, technical language, and the evangelism of pioneers has
      left confusion in its wake.

PMID- 15851445
TI  - Pain.

PMID- 15851446
TI  - Informed choice: why measuring behaviour is important.

PMID- 15851447
TI  - Cystic fibrosis is no longer an important cause of childhood death in the UK.

PMID- 15851448
TI  - Home management versus inpatient care of adolescents with newly diagnosed type 1
      diabetes mellitus: survey of current practice.

PMID- 15851449
TI  - Fostering civic professionalism in tomorrow's doctors.

PMID- 15851450
TI  - Forecasting residents' performance--partly cloudy.
AB  - The authors offer a practical guide for improving the appraisal of a resident's
      performance. They identify six major factors that compromise the process of
      observing, measuring, and characterizing a resident's current performance,
      forecasting future performance, and making decisions about the resident's
      progress. Factors that compromise any of these steps lead to individual and
      collective uncertainty and decrease faculty confidence when making decisions on a
      resident's progress. The six factors, addressed in order of importance, are
      inaccuracies due to (1) incomplete sampling of performance, (2) rater memory
      constraints, (3) hidden performance deficits of the resident, (4) lack of
      performance benchmarks, (5) faculty members' hesitancy to act on negative
      performance information, and (6) systematic rater error. The description of each
      factor is followed by a number of specific suggestions on what residency programs
      can do to eliminate or minimize the impact of these factors. While this article
      is couched in the context of the performance evaluation of residents, everything
      included pertains to measuring and appraising medical students' and practicing
      physicians' clinical performance as well.

PMID- 15851451
TI  - Promoting fundamental clinical skills: a competency-based college approach at the
      University of Washington.
AB  - The focus on fundamental clinical skills in undergraduate medical education has
      declined over the last several decades. Dramatic growth in the number of faculty
      involved in teaching and increasing clinical and research commitments have
      contributed to depersonalization and declining individual attention to students.
      In contrast to the close teaching and mentoring relationship between faculty and
      students 50 years ago, today's medical students may interact with hundreds of
      faculty members without the benefit of a focused program of teaching and
      evaluating clinical skills to form the core of their four-year curriculum.
      Bedside teaching has also declined, which may negatively affect clinical skills
      development. In response to these and other concerns, the University of
      Washington School of Medicine has created an integrated developmental curriculum
      that emphasizes bedside teaching and role modeling, focuses on enhancing
      fundamental clinical skills and professionalism, and implements these goals via a
      new administrative structure, the College system, which consists of a core of
      clinical teachers who spend substantial time teaching and mentoring medical
      students. Each medical student is assigned a faculty mentor within a College for
      the duration of his or her medical school career. Mentors continuously teach and
      reflect with students on clinical skills development and professionalism and,
      during the second year, work intensively with them at the bedside. They also
      provide an ongoing personal faculty contact. Competency domains and benchmarks
      define skill areas in which deepening, progressive attention is focused
      throughout medical school. This educational model places primary focus on the
      student.

PMID- 15851452
TI  - An oral health curriculum for medical students at the University of Washington.
AB  - Oral health disparities are a major public health problem, according to the U.S.
      Surgeon General. Physicians could help prevent oral disease, but lack the
      knowledge to do so. To create an oral health curriculum for medical students at
      the University of Washington School of Medicine, the authors (beginning in 2003)
      (1) reviewed current evidence of medical education and physician training in oral
      health, (2) developed oral health learning objectives and competencies
      appropriate for medical students, and (3) identified current oral health content
      in the undergraduate curriculum and opportunities for including additional
      material. The authors identified very few Medline articles on medical student
      education and training in oral health. The United States Medical Licensing
      Examination Steps 2 and 3 require specific clinical knowledge and skills in oral
      and dental disorders, but other national curriculum databases and the Web site of
      the Liaison Committee on Medical Education devote no significant attention to
      oral health. To develop learning objectives, the authors reviewed major oral
      health reports, online oral health educational resources, and consulted with
      dental faculty. The curriculum was assessed by interviewing key medical school
      faculty and analyzing course descriptions, and was found to be deficient in oral
      health content. The authors developed five learning themes: dental public health,
      caries, periodontal disease, oral cancer, and oral-systemic interactions, and
      recommend the inclusion of corresponding competencies in targeted courses through
      a spiral curriculum. Current progress, the timeline for curriculum changes at the
      University of Washington, and the ethical values and attitudinal shifts needed to
      support this effort are discussed.

PMID- 15851454
TI  - Illness in context and families as teachers: a year-long project for medical
      students.
AB  - The authors describe a program for second-year students in Tel Aviv University's
      six-year medical school. The program's aim is to teach students the importance of
      context and interactions in patient care by exposing them to a real patient
      family-doctor interaction using narrative-based methods to encourage reflective
      learning. Each student meets five times a year with a volunteer family, one of
      whose members suffers from a chronic disease. The program endorses a "patients as
      teachers" approach, as families are considered to be teachers for the students
      and not as objects of investigation and assessment. The students receive
      supervision in small groups, to enhance learning and reflection. To appraise the
      extent to which students had obtained the required knowledge, skills, and
      attitudes, the authors extracted reflections regarding the learning experience
      from students' essays. Major themes identified were becoming "family sensitive,"
      building and improving communication skills, questioning intrusiveness, adopting
      a nonpatronizing and nonjudgmental attitude, developing reflective skills,
      creating a future professional model, and experiencing and appreciating
      continuity of care. The authors argue that learning to listen to patients'
      narratives, developing a reflective attitude, and being sensitive to patient
      family-doctor interactions are of value to all doctors, and therefore programs
      similar to theirs should be established as part of general medical school
      education and not just in the context of family medicine.

PMID- 15851453
TI  - The Health Policy and Legislative Awareness Initiative at the Pennsylvania State
      University College of Medicine: theory meets practice.
AB  - In a constantly evolving health care landscape shaped by many voices--including
      those of third party payers and government--physicians must learn to play a more
      proactive role to become better advocates for their patients and to uphold the
      basic tenets of their noble profession. As legislation and public health become
      increasingly intertwined with the practice of medicine, educators must provide
      future physicians with the tools to meet these new challenges. Accordingly, in
      1996 Pennsylvania State University College of Medicine embarked on its Health
      Policy and Legislative Awareness Initiative, a medical school elective designed
      to provide theoretical knowledge as well as practical experience in legislative
      and policy issues for future physicians early in their careers. The Initiative
      has three key elements: a series of lectures taught by national and local experts
      covering a basic health policy curriculum, a mini-internship conducted at the
      office of a Pennsylvania State legislator, and a practical assignment leading to
      authorship of a resolution to a national medical organization or assisting in
      drafting a bill intended for introduction to the Pennsylvania State Legislature.
      Following several years of successful implementation and a moderate growth in
      enrollment, recent changes in the local and national scene have peaked the
      interest of most students to learn about the system in which they will practice
      medicine. Therefore, in addition to describing the Initiative in its current
      form, the authors discuss future plans for expanded elective opportunities and
      consider the issue of integrating health policy education into core medical
      school curricula.

PMID- 15851455
TI  - Viewpoint: pancakes and medical statistics.
AB  - Everyone is willing to expend considerable effort seeking authenticity; for
      example, the author sometimes travels over 100 miles to eat authentic and
      delicious homemade pancakes in a small-town restaurant. In the same way,
      physicians seek authenticity of care, which is another way of saying they seek
      the truest knowledge available when treating their patients. Because there are so
      many possible causes of many patients' complaints, physicians invoke the
      statistical theory behind the chief complaint (e.g., Which test for the complaint
      has the highest value?). In a world where medicine must be practiced with
      attention to resources and cost and where the answer must be reached in the
      fewest steps, evidence-based medicine (EBM) has risen to prominence. But how do
      clinicians ensure that the EBM literature is giving them the truest available
      knowledge? The author observes that clinicians and others have trusted the peer
      review system to safeguard them against errors in the clinical literature. But he
      contends that errors are getting through at an increasing rate, and that
      physicians cannot automatically trust the peer-review process. Instead, they must
      become judges of experimental design, statistics, and analysis and assume the
      responsibilities that they had hoped the peer-review system would bear for them.
      He speculates about the reasons that peer review is no longer sufficiently
      ensuring authenticity in the literature. And to alleviate this problem, he
      recommends that current approaches to educating physicians about experimental
      design and statistics be augmented by making a beginning knowledge of statistics
      a requirement for entry into medical school.

PMID- 15851456
TI  - What do phonemes have to do with learning medicine?

PMID- 15851457
TI  - Nicholas Nickleby [excerpt].

PMID- 15851459
TI  - Quality of care in teaching hospitals: a literature review.
AB  - PURPOSE: To compare the quality of care in teaching hospitals with that in
      nonteaching hospitals. METHOD: By performing a literature review via PubMed, the
      author identified and surveyed 23 studies that compared the quality of care in
      teaching hospitals with that in nonteaching hospitals. The studies were published
      from 1989-2004 and in all but one case dealt exclusively with U.S. hospitals.
      RESULTS: The teaching hospitals studied had better-quality measures than did
      nonteaching hospitals in the predominant number of studies reviewed. Process
      measures were significantly better in teaching hospitals in seven of the eight
      studies where such measures were observed, and equal in the other study. Risk
      adjusted mortality was lower in teaching hospitals in nine of the 15 studies
      using that measure, not significantly different in five, and significantly lower
      in nonteaching hospitals in one study (in pediatric intensive care units, even
      though the teaching hospitals had a better process of care). In nonmortality
      outcomes, teaching hospitals were better in one study using that measure; there
      were no significant differences in five other such studies. Major teaching
      hospitals had more favorable outcomes end points than did minor teaching
      hospitals in eight studies in which they were compared. Including only those six
      studies using clinical data for process analysis or risk adjustment, teaching
      hospitals had a better process in all six and lower adjusted mortality in five of
      seven studies where that measure was used. CONCLUSIONS: Overall, the favorable
      results in teaching hospitals extended over a range of locations, conditions, and
      populations, including routine as well as complex conditions. However, the
      quality measured in these studies was not at target levels across the spectrum of
      hospitals. There needs to be a continuous and determined effort for improvement
      in all institutions. It is to be hoped that teaching hospitals will take the lead
      not only in continuously improving their own quality, but also in developing and
      evaluating ever improving methods of quality assessment.

PMID- 15851460
TI  - Lessons from pediatrics residency program directors' experiences with work hour
      limitations in New York State.
AB  - PURPOSE: To evaluate the impact of residency work hour limitations on pediatrics
      residency programs in New York State, and to learn lessons that can be used
      nationally with the implementation of the Accreditation Council of Graduate
      Medical Education's similar rules. METHOD: A three-page questionnaire was mailed
      to all pediatrics residency program directors in New York. The questionnaire
      assessed methods used to accommodate the work hour limitations and perceptions of
      the limitations' effects. RESULTS: Twenty-one program directors responded (68%).
      Only large programs used night floats and night teams to meet work hour
      requirements. Programs of all sizes and in all settings used cross coverage and
      sent residents home immediately post call. About half of the programs hired
      additional nonresident staff, usually nurse practitioners, physician assistants,
      and/or attendings. The most frequently reported effects were decreases in the
      amount of time residents spent in inpatient settings, patient continuity in
      inpatient settings, flexibility of residents' scheduling, and increased
      logistical work needed to maintain continuity clinic. A summary of advice to
      other program directors was "be creative" and "be flexible." CONCLUSIONS: New
      York's pediatrics residency programs used a variety of mechanisms to meet work
      hour restrictions. Smaller programs had fewer methods available to them to meet
      such restrictions. Although the logistical work needed to maintain continuity
      clinic increased greatly, continuity and outpatient settings themselves were not
      greatly affected by work hour limitations. Inpatient settings were more affected
      and experienced much more in the way of change.

PMID- 15851461
TI  - U.S. citizens who graduated from medical schools outside the United States and
      Canada and received certification from the Educational Commission for Foreign
      Medical Graduates, 1983-2002.
AB  - PURPOSE: To provide a descriptive overview of international medical school
      graduates (IMGs), U.S. and non-U.S. citizens, who obtained their medical degrees
      outside of the United States and Canada, with a focus on where U.S. citizens
      received their medical education and how this choice has changed over time.
      METHOD: The study group included all IMGs (n = 143,926) certified by the
      Educational Commission for Foreign Medical Graduates (ECFMG) from 1983-2002.
      Descriptive statistics were calculated, including historical certification rates
      for non-U.S. citizen and U.S. citizen IMGs. For IMGs who were U.S. citizens (n =
      18,762), the data were summarized by medical school and country of medical
      school. RESULTS: U.S. citizens who attended medical schools abroad were more
      likely to attend schools in Central America and the Caribbean than in any other
      geographic region. There was a steady decrease in the number of U.S. citizens
      graduating from European medical schools. Conversely, the number graduating from
      medical schools in India and Israel rose. Over the period studied, the regions of
      Africa, Oceania, and South America graduated relatively few U.S. citizens.
      CONCLUSIONS: From 1983-2002, U.S. citizens graduated from medical schools in
      Central America and the Caribbean more than any other geographic region. Studying
      the characteristics of medical schools in this region and their similarities to
      U.S. medical schools, such as a four-year curriculum, may explain why U.S.
      citizens are attracted to this region in large numbers. Additional studies
      focusing on the characteristics of medical schools that train IMGs, the
      performance of the graduates, and their posttraining practice patterns are
      warranted.

PMID- 15851462
TI  - Participation of internal medicine department chairs in the internal medicine
      clerkship--results of a national survey.
AB  - PURPOSE: To characterize the involvement of internal medicine department chairs
      in the core third-year internal medicine clinical clerkship. METHOD: In 2003, the
      Clerkship Directors in Internal Medicine (CDIM) surveyed its membership. Along
      with demographics, clerkship directors were asked if the department's chair
      participated in the clerkship, the number of hours per month the clerkship
      director and chair discussed clerkship issues, and if published job expectations
      were discussed. RESULTS: The response rate was 62% (158/254): 103 responses (89
      clerkship directors) represented unique medical schools, which formed the basis
      of the analysis. Eighty-two percent (84/103) reported the chair taught in the
      clerkship: 54% as teaching attending, 53% as ward attending, 13% as ambulatory
      attending, and 20% other (e.g., lectures, student rounds, morning report). Of
      them, 36% performed two activities; 14% three activities; and 2% four activities.
      Thirty-six percent of the clerkship directors discussed published expectations
      with their chair. They spent 1.7 (SD 2.2) hours per month with the chair
      discussing clerkship issues. However, 17% spent zero hours per month with the
      chair, and 29% spent zero hours per month with a dean's office representative.
      Chairs who taught spent more time each month with the clerkship director compared
      with chairs who did not teach (1.9 versus .82 hours, p = .01, Mann-Whitney).
      There was no association between the chairs' teaching and clerkship directors'
      demographics. CONCLUSIONS: Internal medicine department chairs are significantly
      involved in the clinical education of medical students, both administratively and
      through direct teaching. Chairs who teach spend more time discussing clerkship
      issues with the clerkship director. Chairs and clerkship directors should discuss
      expectations, and chairs should continue to visibly demonstrate their commitment
      to students' education.

PMID- 15851463
TI  - Medical students' knowledge of the U.S. health care system and their preferences
      for curricular change: a national survey.
AB  - PURPOSE: To measure medical students' knowledge of central issues in the U.S.
      health care system and to understand their perception of the importance and
      quality of health policy curricula at their medical schools. METHOD: A
      questionnaire was developed using facts from recent national and international
      health reports to test students' knowledge of health policy. The instrument,
      containing 14 questions about health policy and four questions about school
      curriculum on health policy, was mailed to a national probability sample of 516
      first-year and 847 fourth-year students in the United States. Chi-square and t
      tests were used to compare the responses of first- and fourth-year students.
      RESULTS: A total of 295 first-year (57%) and 475 fourth-year students (56%)
      responded. Nearly all respondents were aware of the adverse health consequences
      for the uninsured, but 40% of first- and fourth-year students underestimated the
      numbers of uninsured in the United States. Thirty-two percent of respondents
      incorrectly answered that the United States had the highest life expectancy of
      any nation, and 27% were not aware that the United States has the highest health
      cost per-person of any nation. First- and fourth-year students performed
      similarly on knowledge questions. Ninety-six percent of respondents felt that
      knowledge of health policy is important to their career, and 54% expressed
      dissatisfaction with the health policy curriculum in medical school. CONCLUSION:
      Medical students have significant gaps in knowledge concerning the U.S. health
      care system. Most students perceive that these deficiencies are not adequately
      addressed in the medical school curriculum.

PMID- 15851464
TI  - Improving resident performance assessment data: numeric precision and narrative
      specificity.
AB  - PURPOSE: To evaluate the use of a systems approach for diagnosing performance
      assessment problems in surgery residencies, and intervene to improve the numeric
      precision of global rating scores and the behavioral specificity of narrative
      comments. METHOD: Faculty and residents at two surgery programs participated in
      parallel before- and-after trials. During the baseline year, quality assurance
      data were gathered and problems were identified. During two subsequent
      intervention years, an educational specialist at each program intervened with an
      organizational change strategy to improve information feedback loops. Three
      quality-assurance measures were analyzed: (1) percentage return rate of forms,
      (2) generalizability coefficients and 95% confidence intervals of scores, and (3)
      percentage of forms with behaviorally specific narrative comments. RESULTS:
      Median return rates of forms increased significantly from baseline to
      intervention Year 1 at Site A (71% to 100%) and Site B (75% to 100%), and then
      remained stable during Year 2. Generalizability coefficients increased between
      baseline and intervention Year 1 at Site A (0.65 to 0.85) and Site B (0.58 to
      0.79), and then remained stable. The 95% confidence interval around resident mean
      scores improved at Site A from baseline to intervention Year 1 (0.78 to 0.58) and
      then remained stable; at Site B, it remained constant throughout (0.55 to 0.56).
      The median percentage of forms with behaviorally specific narrative comments at
      Site A increased significantly from baseline to intervention Years 1 and 2 (50%,
      57%, 82%); at Site B, the percentage increased significantly in intervention Year
      1, and then remained constant (50%, 60%, 67%). CONCLUSIONS: Diagnosing
      performance assessment system problems and improving information feedback loops
      improved the quality of resident performance assessment data at both programs.

PMID- 15851465
TI  - The relationship between the National Board of Medical Examiners' prototype of
      the Step 2 clinical skills exam and interns' performance.
AB  - PURPOSE: To examine the relationship between graduates' performances on a
      prototype of the National Board of Medical Examiners' Step 2 CS and other
      undergraduate measures with their residency directors' ratings of their
      performances as interns. METHOD: Data were collected for the 2001 and 2002
      graduates from the study institution. Checklist and interpersonal scores from the
      prototype Step 2 CS, along with United States Medical Licensing Examination
      (USMLE) Step 1 and 2 scores and undergraduate grade-point average (GPA), were
      correlated with residency directors' ratings (average score for six competencies,
      quartile ranking, and isolated interpersonal communication competency score).
      Stepwise linear regression was used to identify the best outcome predictors.
      RESULTS: Quartile ranking was more highly correlated with GPA than Step 2 CS
      prototype interpersonal score, USMLE Step 2 score, USMLE Step 1 score, and Step 2
      CS prototype checklist score. The average score on the residency director's
      survey was more highly correlated with GPA than USMLE Step 2 score, USMLE Step 1
      score, Step 2 CS prototype interpersonal score, and Step 2 CS prototype checklist
      score. The best predictors for both quartile ranking and average competency score
      were GPA and Step 2 CS prototype interpersonal score (R(2) = 0.26 and 0.28).
      CONCLUSION: Both scores from the Step 2 CS prototype significantly correlated
      with the interns' quartile ranking and average competency score. Only GPA and
      Step 2 CS prototype interpersonal score accounted for most of the variance of
      performance in the regression model.

PMID- 15851466
TI  - Who are physician-scientists' role models? Gender makes a difference.
AB  - PURPOSE: To determine for educational purposes whether differences exist in the
      role models physician-scientists-in-training or in their early years of career
      development envision when they self-assess their abilities to perform clinical
      research. METHOD: A 35-item clinical research self-efficacy questionnaire was
      administered to 251 health care professionals who attended programs at the
      University of Wisconsin-Madison from 2002-2004. Three questions were included to
      determine the sex, role, and qualities of the expert that are envisioned by
      participants. Frequency distributions were computed for each response and
      variables were compared by gender using chi-square analysis and Fisher exact
      test. RESULTS: Ninety-five physicians-in-training and junior faculty physicians
      responded to the questionnaire. Seventy-one percent of female and 95% of male
      respondents reported their envisioned experts to be male. The most frequently
      reported role of the envisioned expert was that of a mentor who was a faculty
      member in the respondent's own department (72% women, 60% men). The three most
      frequently reported qualities of the envisioned expert were "multiple
      publications," "scientific knowledge," and "supportiveness." However, women more
      frequently reported "communication skills" and "problem-solving abilities" than
      did men. This difference was statistically significant and largely due to the
      frequency of qualities selected by women whose envisioned expert was female.
      CONCLUSIONS: The results of this study emphasized the importance of a role
      model's gender in the career development of physician-scientists.

PMID- 15851467
TI  - Career plans for trainees in internal medicine residency programs.
AB  - PURPOSE: Fewer medical students are pursuing residency training in primary care
      disciplines. This report describes the career plans of residents enrolled in
      internal medicine training programs and their reasons for pursuing either
      generalist or subspecialist career paths. METHOD: From 1998 to 2003,
      questionnaires were administered to residents participating in the Internal
      Medicine In-Training Examination. Each year, the survey included questions on
      career choices. In 2002, residents completed a more detailed survey about the
      specific reasons for their career choices. The authors report their responses.
      RESULTS: There has been a steady decline in the percentage of internal medicine
      residents planning to pursue generalist careers. In 1998, 54% of PGY3s planned to
      practice general internal medicine compared with 27% in 2003. Strikingly, in
      2003, only 19% of PGY1s planned to pursue careers in general medicine. Residents
      choosing careers as generalists were influenced by opportunities for long-term
      relationships with patients, a broad content area of practice, caring for
      ambulatory patients, and time with family. The specific reasons for choosing one
      subspecialty over another varied greatly among the subspecialty disciplines.
      Women residents preferred disciplines that allowed more time for family. Both
      genders were attracted to a particular subspecialty for similar reasons.
      CONCLUSIONS: There has been a dramatic decrease in the number of internal
      medicine residents planning to pursue careers in general medicine. This trend
      will likely continue for the next few years, at least, and may have an impact on
      the manner in which the health needs of patients are met in the future.

PMID- 15851468
TI  - Crystal structure of BMP-9 and functional interactions with pro-region and
      receptors.
AB  - Bone morphogenetic proteins (BMPs), a subset of the transforming growth factor
      (TGF)-beta superfamily, regulate a diverse array of cellular functions during
      development and in the adult. BMP-9 (also known as growth and differentiation
      factor (GDF)-2) potently induces osteogenesis and chondrogenesis, has been
      implicated in the differentiation of cholinergic neurons, and may help regulate
      glucose metabolism. We have determined the structure of BMP-9 to 2.3 A and
      examined the differences between our model and existing crystal structures of
      other BMPs, both in isolation and in complex with their receptors. TGF-beta
      ligands are translated as precursors, with pro-regions that generally dissociate
      after cleavage from the ligand, but in some cases (including GDF-8 and TGF-beta1,
      -2, and -3), the pro-region remains associated after secretion from the cell and
      inhibits binding of the ligand to its receptor. Although the proregion of BMP-9
      remains tightly associated after secretion, we find, in several cell-based
      assays, that the activities of BMP-9 and BMP-9.pro-region complex were
      equivalent. Activin receptor-like kinase 1 (ALK-1), an orphan receptor in the TGF
      beta family, was also identified as a potential receptor for BMP-9 based on
      surface plasmon resonance studies (BIAcore) and the ability of soluble ALK-1 to
      block the activity of BMP-9.pro-region complex in cell-based assays.

PMID- 15851470
TI  - Stearoyl-CoA desaturase is involved in the control of proliferation, anchorage
      independent growth, and survival in human transformed cells.
AB  - Saturated and monounsaturated fatty acids are the most abundant fatty acid
      species in mammalian organisms, and their distribution is regulated by stearoyl
      CoA desaturase, the enzyme that converts saturated into monounsaturated fatty
      acids. A positive correlation between high monounsaturated fatty acid levels and
      neoplastic transformation has been reported, but little is still known about the
      regulation of stearoyl-CoA desaturase in cell proliferation and apoptosis, as
      well as in cancer development. Here we report that simian virus 40-transformed
      human lung fibroblasts bearing a knockdown of human stearoyl-CoA desaturase by
      stable antisense cDNA transfection (hSCDas cells) showed a considerable reduction
      in monounsaturated fatty acids, cholesterol, and phospholipid synthesis, compared
      with empty vector transfected-simian virus 40 cell line (control cells). hSCDas
      cells also exhibited high cellular levels of saturated free fatty acids and
      triacylglycerol. Interestingly, stearoyl-CoA desaturase-depleted cells exhibited
      a dramatic decrease in proliferation rate and abolition of anchorage-independent
      growth. Prolonged exposure to exogenous oleic acid did not reverse either the
      slower proliferation or loss of anchorage-independent growth of hSCDas cells,
      suggesting that endogenous synthesis of monounsaturated fatty acids is essential
      for rapid cell replication and invasiveness, two hallmarks of neoplastic
      transformation. Moreover, apoptosis was increased in hSCDas cells in a ceramide
      independent manner. Finally, stearoyl-CoA desaturase-deficient cells were more
      sensitive to palmitic acid-induced apoptosis compared with control cells. Our
      data suggest that, by globally regulating lipid metabolism, stearoyl-CoA
      desaturase activity modulates cell proliferation and survival and emphasize the
      important role of endogenously synthesized monounsaturated fatty acids in
      sustaining the neoplastic phenotype of transformed cells.

PMID- 15851469
TI  - Enhanced shutoff of phototransduction in transgenic mice expressing
      palmitoylation-deficient rhodopsin.
AB  - Palmitoylation is a reversible, post-translational modification observed in a
      number of G-protein-coupled receptors. To gain a better understanding of its role
      in visual transduction, we produced transgenic knock-in mice that expressed a
      palmitoylation-deficient rhodopsin (Palm(-/-)). The mutant rhodopsin was
      expressed at wild-type levels and showed normal cellular localization to rod
      outer segments, indicating that neither rhodopsin stability nor its intracellular
      trafficking were compromised. But Palm(-/-) rods had briefer flash responses and
      reduced sensitivity to flashes and to steps of light. Upon exposure to light,
      rhodopsin became phosphorylated at a faster rate in mutant than in wild-type
      retinas. Since quench of rhodopsin begins with its phosphorylation, these results
      suggest that palmitoylation may modulate rod photoreceptor sensitivity by
      permitting rhodopsin to remain active for a longer period.

PMID- 15851471
TI  - Platelet endothelial aggregation receptor 1 (PEAR1), a novel epidermal growth
      factor repeat-containing transmembrane receptor, participates in platelet contact
      induced activation.
AB  - The present study was designed to identify novel membrane proteins that signal
      during platelet aggregation. Because one putative mechanism for signaling by a
      membrane protein involves phosphorylation, we used oligonucleotide-based
      microarray analyses and mass spectrometric proteomics techniques to specifically
      discover membrane proteins and also identify those proteins that become
      phosphorylated on tyrosine, threonine, or serine residues upon platelet
      aggregation. Surprisingly, both techniques converged to identify a novel membrane
      protein we have termed PEAR1 (platelet endothelial aggregation receptor 1).
      Sequence analysis of PEAR1 predicts a type-1 membrane protein, 15 extracellular
      epidermal growth factor-like repeats, and multiple cytoplasmic tyrosines.
      Analysis of the tissue distribution of PEAR1 showed that it was most highly
      expressed in platelets and endothelial cells. Upon platelet aggregation induced
      by physiological agonists, PEAR1 became phosphorylated on tyrosine (Tyr-925), and
      serine (Ser-953 and Ser-1029) residues. PEAR1 tyrosine phosphorylation was
      blocked by eptifibatide, an alpha(IIb)beta(3) antagonist, which inhibits platelet
      aggregation. Immune clustering of PEAR1 resulted in PEAR1 phosphorylation.
      Aggregation-induced PEAR1 tyrosine phosphorylation lead to the subsequent
      association with the ShcB adaptor protein. Platelet proximity induced by
      centrifugation also induced PEAR1 tyrosine phosphorylation, a reaction not
      inhibited by eptifibatide. These data suggest that PEAR1 is a novel platelet
      receptor that signals secondary to alpha(IIb)beta(3)-mediated platelet-platelet
      contacts.

PMID- 15851472
TI  - Manganese activation of superoxide dismutase 2 in the mitochondria of
      Saccharomyces cerevisiae.
AB  - Manganese-dependent superoxide dismutase 2 (SOD2) in the mitochondria plays a key
      role in protection against oxidative stress. Here we probed the pathway by which
      SOD2 acquires its manganese catalytic cofactor. We found that a mitochondrial
      localization is essential. A cytosolic version of Saccharomyces cerevisiae Sod2p
      is largely apo for manganese and is only efficiently activated when cells
      accumulate toxic levels of manganese. Furthermore, Candida albicans naturally
      produces a cytosolic manganese SOD (Ca SOD3), yet when expressed in the cytosol
      of S. cerevisiae, a large fraction of Ca SOD3 also remained manganese-deficient.
      The cytosol of S. cerevisae cannot readily support activation of Mn-SOD
      molecules. By monitoring the kinetics for metalation of S. cerevisiae Sod2p in
      vivo, we found that prefolded Sod2p in the mitochondria cannot be activated by
      manganese. Manganese insertion is only possible with a newly synthesized
      polypeptide. Furthermore, Sod2p synthesis appears closely coupled to Sod2p
      import. By reversibly blocking mitochondrial import in vivo, we noted that newly
      synthesized Sod2p can enter mitochondria but not a Sod2p polypeptide that was
      allowed to accumulate in the cytosol. We propose a model in which the insertion
      of manganese into eukaryotic SOD2 molecules is driven by the protein unfolding
      process associated with mitochondrial import.

PMID- 15851473
TI  - Inactivation of SRC family tyrosine kinases by reactive oxygen species in vivo.
AB  - Reactive oxygen species, including H2O2, O2*- and OH* are constantly produced in
      the human body and are involved in the development of cardiovascular diseases.
      Emerging evidence suggests that reactive oxygen species, besides their
      deleterious effects at high concentrations, may be protective. However, the
      mechanism underlying the protective effects of reactive oxygen species is not
      clear. Here, we reported a novel finding that H2O2 at low to moderate
      concentrations (50-250 microM) markedly inactivated Src family tyrosine kinases
      temporally and spatially in vivo but not in vitro. We further showed that Src
      family kinases localized to focal adhesions and the plasma membrane were rapidly
      and permanently inactivated by H2O2, which resulted from a profound reduction in
      phosphorylation of the conserved tyrosine residue at the activation loop.
      Interestingly, the cytoplasmic Src family kinases were activated gradually by
      H2O2, which partially compensated for the loss of total activities of Src family
      kinases but not their functions. Finally, H2O2 rendered endothelial cells
      resistant to growth factors and cytokines and protected the cells from
      inflammatory activation. Because Src family kinases play key roles in cell
      signaling, the rapid inactivation of Src family kinases by H2O2 may represent a
      novel mechanism for the protective effects of reactive oxygen species.

PMID- 15851474
TI  - Proteomic analysis of protein nitration in aging skeletal muscle and
      identification of nitrotyrosine-containing sequences in vivo by nanoelectrospray
      ionization tandem mass spectrometry.
AB  - The nitration of protein tyrosine residues represents an important post
      translational modification during development, oxidative stress, and biological
      aging. To rationalize any physiological changes with such modifications, the
      actual protein targets of nitration must be identified by proteomic methods.
      While several studies have used proteomics to screen for 3-nitrotyrosine
      containing proteins in vivo, most of these studies have failed to prove nitration
      unambiguously through the actual localization of 3-nitrotyrosine to specific
      sequences by mass spectrometry. In this paper we have applied sequential solution
      isoelectric focusing and SDS-PAGE for the proteomic characterization of specific
      3-nitrotyrosine-containing sequences of nitrated target proteins in vivo using
      nanoelectrospray ionization-tandem mass spectrometry. Specifically, we analyzed
      proteins from the skeletal muscle of 34-month-old Fisher 344/Brown Norway F1
      hybrid rats, a well accepted animal model for biological aging. We identified the
      3-nitrotyrosine-containing sequences of 11 proteins, including cytosolic creatine
      kinase, tropomyosin 1, glyceraldehyde-3-phosphate dehydrogenase, myosin light
      chain, aldolase A, pyruvate kinase, glycogen phosphorylase, actinin, gamma-actin,
      ryanodine receptor 3, and neurogenic locus notch homolog. For creatine kinase and
      neurogenic locus notch homolog, two 3-nitrotyrosine-containing sequences were
      identified, i.e. at positions 14 and 20 for creatine kinase and at positions 1175
      and 1205 for the neurogenic locus notch homolog. The selectivity of the in vivo
      nitration of creatine kinase at Tyr14 and Tyr20 does not correspond to the
      product selectivity in vitro, where exclusively Tyr82 was nitrated when creatine
      kinase was exposed to peroxynitrite. The latter experiments demonstrate that the
      in vitro exposure of an isolated protein to peroxynitrite may not always be a
      good model to mimic protein nitration in vivo.

PMID- 15851475
TI  - Intracellular kinase inhibitors selected from combinatorial libraries of designed
      ankyrin repeat proteins.
AB  - The specific intracellular inhibition of protein activity at the protein level
      allows the determination of protein function in the cellular context. We
      demonstrate here the use of designed ankyrin repeat proteins as tailor-made
      intracellular kinase inhibitors. The target was aminoglycoside phosphotransferase
      (3')-IIIa (APH), which mediates resistance to aminoglycoside antibiotics in
      pathogenic bacteria and shares structural homology with eukaryotic protein
      kinases. Combining a selection and screening approach, we isolated 198 potential
      APH inhibitors from highly diverse combinatorial libraries of designed ankyrin
      repeat proteins. A detailed analysis of several inhibitors revealed that they
      bind APH with high specificity and with affinities down to the subnanomolar
      range. In vitro, the most potent inhibitors showed complete enzyme inhibition,
      and in vivo, a phenotype comparable with the gene knockout was observed, fully
      restoring antibiotic sensitivity in resistant bacteria. These results underline
      the great potential of designed ankyrin repeat proteins for modulation of
      intracellular protein function.

PMID- 15851476
TI  - Dual mechanisms whereby a broken RNA end assists the catalysis of its repair by
      T4 RNA ligase 2.
AB  - T4 RNA ligase 2 (Rnl2) efficiently seals 3'-OH/5'-PO4 RNA nicks via three
      nucleotidyl transfer steps. Here we show that the terminal 3'-OH at the nick
      accelerates the second step of the ligase pathway (adenylylation of the 5'-PO4
      strand) by a factor of 1000, even though the 3'-OH is not chemically transformed
      during the reaction. Also, the terminal 2'-OH at the nick accelerates the third
      step (attack of the 3'-OH on the 5'-adenylated strand to form a phosphodiester)
      by a factor of 25-35, even though the 2'-OH is not chemically reactive. His-37 of
      Rnl2 is uniquely required for step 3, providing a approximately 10(2) rate
      acceleration. Biochemical epistasis experiments show that His-37 and the RNA 2'
      OH act independently. We conclude that the broken RNA end promotes catalysis of
      its own repair by Rnl2 via two mechanisms, one of which (enhancement of step 3 by
      the 2'-OH) is specific to RNA ligation. Substrate-assisted catalysis provides a
      potential biochemical checkpoint during nucleic acid repair.

PMID- 15851477
TI  - Essential role of p38gamma in K-Ras transformation independent of
      phosphorylation.
AB  - MAPK cascades play the critical role in regulating Ras oncogene activity by
      phosphorylation-dependent mechanisms. Whereas the ERK MAPK pathway is required
      for Ras transformation, our previous works established that the p38 activity is
      inhibitory to Ras signaling in both experimental and ras-mutated cancer cells
      (Chen, G., Hitomi, M., Han, J., and Stacey, D. W. (2000) J. Biol. Chem. 275,
      38973-38980; Qi, X., Tang, J., Pramanik, R., Schultz, R. M., Shirasawa, S.,
      Sasazuki, T., Han, J., and Chen, G. (2004) J. Biol. Chem., 279, 22138-22144).
      Here we report that K-Ras activated p38gamma, a p38 MAPK family member, by
      inducing its expression without increasing its phosphorylation and that depletion
      of induced p38gamma suppressed Ras transformation in rat intestinal epithelial
      cells. This p38gamma activity contrasts with that of its family member, p38alpha,
      which is activated by Ras through phosphorylation, leading to an inhibition of
      Ras transformation. Mechanistic analyses showed that unphosphorylated p38gamma
      may promote Ras transformation through an increased complex formation with ERK
      proteins. Significantly, functional p38gamma protein was expressed only in K-ras
      mutated human colon cancer cells, and p38gamma transcripts were ubiquitously
      increased in a set of primary human colon cancer tissues. These studies thus
      demonstrate the essential role of p38gamma in K-Ras transformation independent of
      phosphorylation, and elevated p38gamma may serve as a novel diagnostic marker and
      therapeutic target for human colon cancer.

PMID- 15851478
TI  - Regulation of endothelial argininosuccinate synthase expression and NO production
      by an upstream open reading frame.
AB  - Argininosuccinate synthase (AS) catalyzes the rate-limiting step in the recycling
      of citrulline to arginine, which in endothelial cells, is tightly coupled to the
      production of nitric oxide (NO). In previous work, we established that
      endothelial AS mRNA can be initiated from multiple start sites, generating co
      expressed mRNA variants with different 5'-untranslated regions (5'-UTRs). One of
      the 5'-UTRs, the shortest form, represents greater than 90% of the total AS mRNA.
      Two other extended 5'-UTR forms of AS mRNA, resulting from upstream initiations,
      contain an out-of-frame, upstream open reading frame (uORF). In this study, the
      function of the extended 5'-UTRs of AS mRNA was investigated. Single base
      insertions to place the uORF in-frame, and mutations to extend the uORF,
      demonstrated functionality, both in vitro with AS constructs and in vivo with
      luciferase constructs. Overexpression of the uORF suppressed endothelial AS
      protein expression, whereas specific silencing of the uORF AS mRNAs resulted in
      the coordinate up-regulation of AS protein and NO production. Expression of the
      full-length of the uORF was necessary to mediate a trans-suppressive effect on
      endothelial AS expression, demonstrating that the translation product itself
      affects regulation. In conclusion, the uORF found in the extended, overlapping 5'
      UTR AS mRNA species suppresses endothelial AS expression, providing a novel
      mechanism for regulating endothelial NO production by limiting the availability
      of arginine.

PMID- 15851479
TI  - The codon 47 polymorphism in p53 is functionally significant.
AB  - In addition to a common polymorphism at codon 72, the p53 tumor suppressor gene
      also contains a rare single nucleotide polymorphism at amino acid 47. Wild type
      p53 encodes proline at this residue, but in <5% of African Americans, this amino
      acid is serine. Notably, phosphorylation of the adjacent serine 46 by the proline
      directed kinase p38 MAPK is known to greatly enhance the ability of p53 to induce
      apoptosis. Here we showed that the serine 47 polymorphic variant, which replaces
      the proline residue necessary for recognition by proline-directed kinases, is a
      markedly poorer substrate for phosphorylation on serine 46 by p38 MAPK.
      Consistent with this finding, we showed that the serine 47 variant has up to 5
      fold decreased ability to induce apoptosis compared with wild type p53.
      Mechanistically, we found that this variant has decreased ability to
      transactivate two p53 target genes, p53AIP1 and PUMA, but not other p53 response
      genes; this is the first time that phosphorylation of serine 46 has been
      implicated in transactivation of PUMA by p53. Down-regulation of PUMA in cells
      with wild type p53 using short interfering RNAs reduced apoptosis in these cells
      to a level comparable to that in cells containing the serine 47 variant. The
      combined data indicated that, like the codon 72 polymorphism, the codon 47
      polymorphism of p53 is functionally significant and may play a role in cancer
      risk, progression, and the efficacy of therapy.

PMID- 15851480
TI  - Differential Involvement of ERK2 and p38 in platelet adhesion to collagen.
AB  - We investigated the role of two MAP kinases, ERK2 and p38, in platelet adhesion
      and spreading over collagen matrix in static and blood flow conditions. P38 was
      involved in collagen-induced platelet adhesion and spreading in static adhesion
      conditions, whereas ERK2 was not. In blood flow conditions, with shear rates of
      300 or 1500 s(-1), ERK2 and p38 displayed differential involvement in platelet
      adhesion, depending on the presence or absence of the von Willebrand factor
      (vWF). Low collagen coverage densities (0.04 microg/cm2) did not support vWF
      binding. During perfusions over this surface, platelet adhesion was not affected
      by the inhibition of ERK2 phosphorylation by PD 98059. However, abolishing p38
      activation by SB 203580 treatment reduced platelet adhesion by 67 +/- 9% at 300
      s(-1) and 56 +/- 2% at 1500 s(-1). In these conditions, the p38 activity required
      for platelet adhesion depends on the alpha2beta1 collagen receptor. At higher
      collagen coverage densities (0.8 microg/cm2) supporting vWF binding, the
      inhibition of ERK2 activity by PD 98059 decreased adhesion by 47 +/- 6% at 300 s(
      1) and 72 +/- 3% at 1500 s(-1), whereas p38 inhibition had only a small effect.
      The ERK2 activity required for platelet adhesion was dependent on the interaction
      of vWF with GPIb. In conclusion, ERK2 and p38 have complementary effects in the
      control of platelet adhesion to collagen in a shear stress-dependent manner.

PMID- 15851481
TI  - Nuclear matrix binding regulates SATB1-mediated transcriptional repression.
AB  - Special AT-rich binding protein 1 (SATB1) originally was identified as a protein
      that bound to the nuclear matrix attachment regions (MARs) of the immunoglobulin
      heavy chain intronic enhancer. Subsequently, SATB1 was shown to repress many
      genes expressed in the thymus, including interleukin-2 receptor alpha, c-myc, and
      those encoded by mouse mammary tumor virus (MMTV), a glucocorticoid-responsive
      retrovirus. SATB1 binds to MARs within the MMTV provirus to repress
      transcription. To address the role of the nuclear matrix in SATB1-mediated
      repression, a series of SATB1 deletion constructs was used to determine protein
      localization. Wild-type SATB1 localized to the soluble nuclear, chromatin, and
      nuclear matrix fractions. Mutants lacking amino acids 224-278 had a greatly
      diminished localization to the nuclear matrix, suggesting the presence of a
      nuclear matrix targeting sequence (NMTS). Transient transfection experiments
      showed that NMTS fusions to green fluorescent protein or LexA relocalized these
      proteins to the nuclear matrix. Difficulties with previous assay systems prompted
      us to develop retroviral vectors to assess effects of different SATB1 domains on
      expression of MMTV proviruses or integrated reporter genes. SATB1 overexpression
      repressed MMTV transcription in the presence and absence of functional
      glucocorticoid receptor. Repression was alleviated by deletion of the NMTS, which
      did not affect DNA binding, or by deletion of the MAR-binding domain. Our studies
      indicate that both nuclear matrix association and DNA binding are required for
      optimal SATB1-mediated repression of the integrated MMTV promoter and may allow
      insulation from cellular regulatory elements.

PMID- 15851482
TI  - Mirk/Dyrk1B mediates survival during the differentiation of C2C12 myoblasts.
AB  - The kinase Mirk/dyrk1B is essential for the differentiation of C2C12 myoblasts.
      Mirk reinforces the G0/G1 arrest state in which differentiation occurs by
      directly phosphorylating and stabilizing p27(Kip1) and destabilizing cyclin D1.
      We now demonstrate that Mirk is anti-apoptotic in myoblasts. Knockdown of
      endogenous Mirk by RNA interference activated caspase 3 and decreased myoblast
      survival by 75%, whereas transient overexpression of Mirk increased cell
      survival. Mirk exerts its anti-apoptotic effects during muscle differentiation at
      least in part through effects on the cell cycle inhibitor and pro-survival
      molecule p21(Cip1). Overexpression and RNA interference experiments demonstrated
      that Mirk phosphorylates p21 within its nuclear localization domain at Ser-153
      causing a portion of the typically nuclear p21 to localize in the cytoplasm.
      Phosphomimetic GFP-p21-S153D was pancellular in both cycling C2C12 myoblasts and
      NIH3T3 cells. Endogenous Mirk in myotubes and overexpressed Mirk in NIH3T3 cells
      were able to cause the pancellular localization of wild-type GFP-p21 but not the
      nonphosphorylatable mutant GFP-p21-S153A. Translocation to the cytoplasm enables
      p21 to block apoptosis through inhibitory interaction with pro-apoptotic
      molecules. Phosphomimetic p21-S153D was more effective than wild-type p21 in
      blocking the activation of caspase 3. Transient expression of p21-S153D also
      increased myoblast viability in colony forming assays, whereas the p21-S153A
      mutant had no effect. This Mirk-dependent change in p21 intracellular
      localization is a natural part of myoblast differentiation. Endogenous p21
      localized exclusively to the nuclei of proliferating myoblasts but was also found
      in the cytoplasm of post-mitotic multinucleated myotubes and adult human skeletal
      myofibers.

PMID- 15851483
TI  - Multiple mixed lineage leukemia (MLL) fusion proteins suppress p53-mediated
      response to DNA damage.
AB  - Chromosomal translocations involving the mixed lineage leukemia (MLL) gene are
      often observed in acute leukemias of both myeloid and lymphocytic origin.
      Expression of MLL fusion proteins is known to induce malignant transformation of
      normal blood progenitors; however, molecular mechanisms of this process are still
      poorly understood. In this study we investigated the effect of several frequently
      detected MLL fusion proteins on p53 transcriptional activity. Our data show that
      MLL-AF9, MLL-AF10, MLL-ENL, and MLL-ELL substantially down-regulate p53-mediated
      induction of p21, MDM2, and Bax in response to DNA damage. Furthermore, we
      identify the reduction in p53 acetylation by p300 as a major mechanism of the
      inhibitory effect of MLL leukemic fusions. Our data suggest that abrogation of
      p53 functional activity can be a common feature of MLL fusion-mediated
      leukemogenesis.

PMID- 15851484
TI  - Differential requirements for the chemokine receptor CCR7 in T cell activation
      during Listeria monocytogenes infection.
AB  - Effective priming of T cell responses depends on cognate interactions between
      naive T cells and professional antigen-presenting cells (APCs). This contact is
      the result of highly coordinated migration processes, in which the chemokine
      receptor CCR7 and its ligands, CCL19 and CCL21, play a central role. We used the
      murine Listeria monocytogenes infection model to characterize the role of the
      CCR7/CCR7 ligand system in the generation of T cell responses during bacterial
      infection. We demonstrate that efficient priming of naive major
      histocompatibility complex (MHC) class Ia-restricted CD8+ T cells requires CCR7.
      In contrast, MHC class Ib-restricted CD8+ T cells and MHC class II-restricted
      CD4+ T cells seem to be less dependent on CCR7; memory T cell responses are
      independent of CCR7. Infection experiments with bone marrow chimeras or mice
      reconstituted with purified T cell populations indicate that CCR7 has to be
      expressed on CD8+ T cells and professional APCs to promote efficient MHC class Ia
      restricted T cell priming. Thus, different T cell subtypes and maturation stages
      have discrete requirements for CCR7.

PMID- 15851486
TI  - The 3' end of the heavy chain constant region locus enhances germline
      transcription and switch recombination of the four gamma genes.
AB  - The switch in immunoglobulin (Ig) heavy chain class is preceded by germline
      transcription and then mediated by a DNA recombination event. To study germline
      transcription and class switch recombination we used transgenic mice with a 230
      kilobase bacterial artificial chromosome that included a rearranged VDJ gene and
      the entire heavy chain constant region locus. In addition to several lines with
      intact transgenes, we identified two lines in which the heavy chain locus
      transgene lacked Calpha and everything 3' of it, including the regulatory
      elements HS3a, HS1-2, HS3b, and HS4. B cells from both lines with the truncated
      transgenes make abundant transgenic (Tg) VDJCmu transcripts and IgM protein.
      Deletion of the 3' end of the locus results in dramatically reduced expression of
      both germline transcripts and switched VDJCH transcripts of the gamma3, gamma2b,
      gamma2a, and epsilon genes. In addition, the transgenes lacking the 3' end of the
      locus express reduced amounts of gamma1 germline transcripts and 2-3% of the
      amount of Tg IgG1 in tissue culture compared with intact transgenes. Finally,
      switch recombination to gamma1 is undetectable in the transgenes lacking the 3'
      elements, as measured by digestion circularization-polymerase chain reaction or
      by the expression of VDJCgamma1 transcripts.

PMID- 15851487
TI  - Identification of proteoglycans as the APRIL-specific binding partners.
AB  - B cell activating factor of the tumor necrosis factor (TNF) family (BAFF) and a
      proliferation-inducing ligand (APRIL) are closely related ligands within the TNF
      superfamily that play important roles in B lymphocyte biology. Both ligands share
      two receptors--transmembrane activator and calcium signal--modulating cyclophilin
      ligand interactor (TACI) and B cell maturation antigen (BCMA)--that are
      predominantly expressed on B cells. In addition, BAFF specifically binds BAFF
      receptor, whereas the nature of a postulated APRIL-specific receptor remains
      elusive. We show that the TNF homology domain of APRIL binds BCMA and TACI,
      whereas a basic amino acid sequence (QKQKKQ) close to the NH2 terminus of the
      mature protein is required for binding to the APRIL-specific "receptor." This
      interactor was identified as negatively charged sulfated glycosaminoglycan side
      chains of proteoglycans. Although T cell lines bound little APRIL, the ectopic
      expression of glycosaminoglycan-rich syndecans or glypicans conferred on these
      cells a high binding capacity that was completely dependent on APRIL's basic
      sequence. Moreover, syndecan-1-positive plasma cells and proteoglycan-rich
      nonhematopoietic cells displayed high specific, heparin-sensitive binding to
      APRIL. Inhibition of BAFF and APRIL, but not BAFF alone, prevented the survival
      and/or the migration of newly formed plasma cells to the bone marrow. In
      addition, costimulation of B cell proliferation by APRIL was only effective upon
      APRIL oligomerization. Therefore, we propose a model whereby APRIL binding to the
      extracellular matrix or to proteoglycan-positive cells induces APRIL
      oligomerization, which is the prerequisite for the triggering of TACI- and/or
      BCMA-mediated activation, migration, or survival signals.

PMID- 15851485
TI  - A type I interferon autocrine-paracrine loop is involved in Toll-like receptor
      induced interleukin-12p70 secretion by dendritic cells.
AB  - Dendritic cells (DC) produce interleukin-12 (IL-12) in response to Toll-like
      receptor (TLR) activation. Two major TLR signaling pathways participate in the
      response to pathogens: the nuclear factor-kappaB (NF-kappaB)-dependent pathway
      leading to inflammatory cytokine secretion including IL-12 and the interferon
      (IFN)-dependent pathway inducing type I IFN and IFN-regulated genes. Here we show
      that the two pathways cooperate and are likely both necessary for inducing an
      optimal response to pathogens. R-848/Resiquimod (TLR7 ligand in the mouse and
      TLR7/8 ligand in human) synergized with poly(I:C) (TLR3 ligand) or
      lipopolysaccharide (LPS; TLR4 ligand) in inducing high levels of bioactive IL
      12p70 secretion and IFN-beta mRNA accumulation by mouse bone marrow-derived DC
      (BM-DC). Strikingly, IL-12p70 but not IL-12p40 secretion was strongly reduced in
      BM-DC from STAT1(-/-) and IFNAR(-/-) mice. STAT1 tyrosine-phosphorylation, IL
      12p35, and IFN-beta mRNA accumulation were strongly inhibited in IFNAR(-/-) BM-DC
      activated with the TLR ligand combinations. Similar observation were obtained in
      human TLR8-expressing monocyte-derived DC (moDC) using neutralizing anti-IFNAR2
      antibodies, although results also pointed to a possible involvement of IFN
      lambda1 (also known as IL-29). This suggests that TLR engagement on DC induces
      endogenous IFNs that further synergize with the NF-kappaB pathway for optimal IL
      12p70 secretion. Moreover, analysis of interferon regulatory factors (IRF)
      regulation in moDC suggests a role for IRF7/8 in mediating IRF3-independent type
      I IFN and possibly IL-12p35 synthesis in response to TLR7/8.

PMID- 15851488
TI  - Density of the Notch ligand Delta1 determines generation of B and T cell
      precursors from hematopoietic stem cells.
AB  - Notch signaling regulates multiple cell fate decisions by hematopoietic
      precursors. To address whether different amounts of Notch ligand influence
      lineage choices, we cultured murine bone marrow lin(-)Sca-1(+)c-kit+ cells with
      increasing densities of immobilized Delta1(ext-IgG) consisting of the
      extracellular domain of Delta1 fused to the Fc domain of human IgG1. We found
      that relatively lower densities of Delta1(ext-IgG) enhanced the generation of Sca
      1(+)c-kit+ cells, Thy1(+)CD25+ early T cell precursors, and B220(+)CD43(-/lo)
      cells that, when cocultured with OP9 stroma cells, differentiated into CD19+
      early B cell precursors. Higher densities of Delta1(ext-IgG) also enhanced the
      generation of Sca-1(+)c-kit+ precursor cells and promoted the development of
      Thy1(+)CD25+ cells, but inhibited the development of B220(+)CD43(-/lo) cells.
      Analyses of further isolated precursor populations suggested that the enhanced
      generation of T and B cell precursors resulted from the effects on multipotent
      rather than lymphoid-committed precursors. The results demonstrate the density
      dependent effects of Delta1 on fate decisions of hematopoietic precursors at
      multiple maturational stages and substantiate the previously unrecognized ability
      of Delta1 to enhance the development of both early B and T precursor cells.

PMID- 15851490
TI  - Racial, ethnic minorities less likely to receive good cardiac care, studies find.

PMID- 15851491
TI  - Experts find huge gaps in understanding, treating menopause symptoms.

PMID- 15851489
TI  - Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile
      idiopathic arthritis and clinical response to IL-1 blockade.
AB  - Systemic onset juvenile idiopathic arthritis (SoJIA) encompasses approximately
      10% of cases of arthritis that begin in childhood. The disease is unique in terms
      of clinical manifestations, severity of joint involvement, and lack of response
      to tumor necrosis factor blockade. Here, we show that serum from SoJIA patients
      induces the transcription of innate immunity genes, including interleukin (IL)-1
      in healthy peripheral blood mononuclear cells (PBMCs). Upon activation, SoJIA
      PBMCs release large amounts of IL-1beta. We administered recombinant IL-1
      receptor antagonist to nine SoJIA patients who were refractory to other
      therapies. Complete remission was obtained in seven out of nine patients and a
      partial response was obtained in the other two patients. We conclude that IL-1 is
      a major mediator of the inflammatory cascade that underlies SoJIA and that this
      cytokine represents a target for therapy in this disease.

PMID- 15851492
TI  - COX-2 inhibitors still eyed for cancer prevention.

PMID- 15851493
TI  - Stability and sterility of dolasetron mesylate in syringes stored at room
      temperature.

PMID- 15851494
TI  - Lycopene: a word of caution.

PMID- 15851495
TI  - Telithromycin: do we really need this antimicrobial?

PMID- 15851496
TI  - Telithromycin: the first ketolide for the treatment of respiratory infections.
AB  - PURPOSE: The pharmacology, mechanisms of resistance, in vitro activity, clinical
      efficacy, pharmacokinetics, indications, adverse effects, dosage and
      administration, and place in therapy of telithromycin in the treatment of
      respiratory infections are reviewed. SUMMARY: Telithromycin is the first ketolide
      to be approved in the United States for use against common respiratory pathogens.
      The unique structure of telithromycin allows for enhanced binding to bacterial
      ribosomal RNA, thereby blocking protein synthesis. Its spectrum of activity
      includes pathogens implicated in common respiratory infections (Staphylococcus
      aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis,
      Mycoplasma pneumonia, and Chlamydia pneumoniae) and multidrug-resistant isolates
      of pneumococcus. Clinical efficacy has been documented in several multicenter,
      comparative trials for the treatment of community-acquired pneumonia, acute
      exacerbation of chronic bronchitis, acute maxillary sinusitis, and pharyngitis
      tonsillitis. Although studies have demonstrated that the clinical efficacy of
      telithromycin is comparable to macrolides, telithromycin is unique in that it
      provides activity against penicillin- and macrolide-resistant respiratory
      pathogens. The recommended dosage of telithromycin is 800 mg p.o. once daily. The
      most common adverse events resulting from telithromycin use include diarrhea,
      nausea, headache, dizziness, vomiting, loose stools, dysgeusia, and dyspepsia.
      The drug's adverse-event profile is comparable to that of similar agents.
      Telithromycin is a strong inhibitor of cytochrome P-450 isoenzyme 3A4; therefore,
      it can affect the efficacy and toxicity profile of medications that are
      metabolized by this isoenzyme. CONCLUSION: Telithromycin is a reasonable addition
      to the current treatment options for upper-respiratory-tract infections. Its use
      should be restricted to infections caused by penicillin- and macrolide-resistant
      pathogens.

PMID- 15851497
TI  - Use of failure mode and effects analysis in improving the safety of i.v. drug
      administration.
AB  - PURPOSE: Failure mode and effects analysis (FMEA) was used to identify dosing and
      administration errors associated with i.v. medications and evaluate the
      effectiveness of subsequent system improvements. SUMMARY: A multidisciplinary
      medication safety team conducted an FMEA to identify and reduce common medication
      errors and selected wrong-dose errors for process improvement. In 2002, wrong
      dose errors comprised 17% of all medication errors at the hospital (59 of 347
      errors). The most common reason for administering the wrong dose was error in
      programming the i.v. infusion pump (41%). Potential errors (i.e., failures)
      identified were misinterpretation of the order, removing the wrong medication or
      wrong concentration of the correct medication, using the wrong diluent or drug to
      prepare the drip, and entering the wrong concentration or infusion rate on the
      pump. Errors in programming the i.v. infusion pump was the step in the medication
      use process associated with the highest criticality index. Based on the results
      of the FMEA, two main interventions were performed. First, standard order sets
      were revised after streamlining the formulary and eliminating the use of
      unapproved abbreviations. Second, an i.v. pump with enhanced safety features was
      implemented. One-year follow-up data revealed that the number of medication
      errors related to dosing (wrong dose or incorrect infusion rate) had decreased
      slightly (from 59 in 2002 to 46 in 2003); however, a dramatic reduction was noted
      in the percentage of pump-related errors. In 2003, pump-related errors accounted
      for 22% of dosing errors, compared with 41% in 2002. CONCLUSION: Medication
      errors related to i.v. infusion pumps were reduced by conducting an FMEA and
      implementing the process changes needed.

PMID- 15851498
TI  - Cholinesterase inhibitor use in geriatric outpatients with dementia.

PMID- 15851499
TI  - Objective structured clinical examinations for an ambulatory care pharmacy
      rotation.

PMID- 15851500
TI  - Rationale for having a chief pharmacy officer in a health care organization.

PMID- 15851501
TI  - Efficacy of statins in preventing progression of aortic stenosis.

PMID- 15851505
TI  - Drug courts: framing policy to ensure success.

PMID- 15851504
TI  - The beta subunit of the Na+/K+-ATPase follows the conformational state of the
      holoenzyme.
AB  - The Na+/K+-ATPase is a ubiquitous plasma membrane ion pump that utilizes ATP
      hydrolysis to regulate the intracellular concentration of Na+ and K+. It is
      comprised of at least two subunits, a large catalytic alpha subunit that mediates
      ATP hydrolysis and ion transport, and an ancillary beta subunit that is required
      for proper trafficking of the holoenzyme. Although processes mediated by the
      alpha subunit have been extensively studied, little is known about the
      participation of the beta subunit in conformational changes of the enzyme. To
      elucidate the role of the beta subunit during ion transport, extracellular amino
      acids proximal to the transmembrane region of the sheep beta1 subunit were
      individually replaced for cysteines. This enabled sulfhydryl-specific labeling
      with the environmentally sensitive fluorescent dye tetramethylrhodamine-6
      maleimide (TMRM) upon expression in Xenopus oocytes. Investigation by voltage
      clamp fluorometry identified three reporter positions on the beta1 subunit that
      responded with fluorescence changes to alterations in ionic conditions and/or
      membrane potential. These experiments for the first time show real-time detection
      of conformational rearrangements of the Na+/K+-ATPase through a fluorophore
      labeled beta subunit. Simultaneous recording of presteady-state or stationary
      currents together with fluorescence signals enabled correlation of the observed
      environmental changes of the beta subunit to certain reaction steps of the Na+/K+
      ATPase, which involve changes in the occupancy of the two principle
      conformational states, E1P and E2P. From these experiments, evidence is provided
      that the beta1-S62C mutant can be directly used to monitor the conformational
      state of the enzyme, while the F64C mutant reveals a relaxation process that is
      triggered by sodium transport but evolves on a much slower time scale. Finally,
      shifts in voltage dependence and kinetics observed for mutant K65C show that this
      charged lysine residue, which is conserved in beta1 isoforms, directly influences
      the effective potential that determines voltage dependence of extracellular
      cation binding and release.

PMID- 15851503
TI  - Cell-cell interaction underlies formation of fluid in the male reproductive tract
      of the rat.
AB  - The epithelia lining the epididymides of many species consists of several cell
      types. We have provided evidence that the basal cells are essential to the
      integrated functions of the epithelium. Basal cells, but not principal cells, and
      other cells in the epididymis express TRPC3 and COX-1. We have isolated basal
      cells from intact rat epididymis using antibody-coated Dynabeads and subjected
      them to whole-cell patch-clamp measurement of nonselective cation channel
      activity, a feature of TRPC3 protein, and Fluo-3 fluorescence measurement of
      intracellular Ca2+ concentration. The results show that a nonselective cation
      current blockable by La3+ (0.1 mM), Gd3+ (0.1 mM), or SKF96365 (20 microM) could
      be activated by lysylbradykinin (200 nM). In cells loaded with Fluo-3, addition
      of lysylbradykinin (100 nM) caused a sustained increase of intracellular Ca2+.
      This effect was blocked by Gd3+ (0.1 mM) or SKF96365 (20 microM) and was not
      observed in Fluo-3-loaded principal cells. Stimulation of basal cell/principal
      cell cocultures with lysylbradykinin (200 nM) evoked in principal cells a current
      with CFTR-Cl- channel characteristics. Isolated principal cells in the absence of
      basal cells did not respond to lysylbradykinin but responded to PGE2 (100 nM)
      with activation of a CFTR-like current. Basal cells, but not principal cells,
      released prostaglandin E2 when stimulated with lysylbradykinin (100 nM). The
      release was blocked by SKF96365 (20 microM) and BAPTA-AM (0.05 or 0.1 mM).
      Confluent cell monolayers harvested from a mixture of disaggregated principal
      cells and basal cells responded to lysylbradykinin (100 nM) and PGE2 (500 nM)
      with an increase in electrogenic anion secretion. The former response was
      dependent on prostaglandin synthesis as piroxicam blocked the response. However,
      cell cultures obtained from principal cells alone responded to PGE2 but not to
      bradykinin. These results support the notion that basal cells regulate principal
      cells through a Ca2+ and COX signaling pathway.

PMID- 15851506
TI  - Lifting the cover on drug courts: evaluation findings and policy concerns.
AB  - Drug treatment courts emerged in 1989 as a court-based solution to an enormous
      increase of drug-related arrests. Since their inception, drug treatment courts
      have been subject to empirical and process evaluations to provide quantitative
      and qualitative data regarding their effectiveness. This article reviews the
      extant literature on the effectiveness of drug treatment courts and discusses
      findings regarding various components of the criminal justice system. It is
      argued that based on empirical evaluation findings, drug treatment courts have
      achieved success in lowering rates of recidivism among drug offenders, despite
      problematic methodological and analytical concerns. This article also presents
      key components and agents of drug treatment courts and discusses their impact and
      relevance to policy creation and adaptation. It is suggested that when combined
      with empirical evaluations, process evaluations provide great insight into the
      drug-treatment-court dynamic. This article concludes with a discussion of the
      implications of drug treatment courts for justice policy.

PMID- 15851508
TI  - Intellectual abilities and motivation toward substance abuse treatment in drug
      involved offenders: a pilot study in the Belgian criminal justice system.
AB  - A sample of Belgian drug-involved inmates (N=116) completed the European
      Addiction Severity Index, the Raven Standard Progressive Matrices (SPM), and the
      Circumstances, Motivation, and Readiness Scales. The pilot results demonstrate
      that nearly 50% of the participating drug-involved offenders display low
      intellectual abilities (SPM score definitely below average). Legal difficulties,
      drug abuse, and psychological problems are identified as the most severe problem
      areas for the total group. The participants display low to moderately low scores
      regarding motivation, readiness, and external reasons to stay in or leave
      treatment. No to very limited correlations between motivational attributes and
      other variables such as the length of the prison sentence and the number of
      violent crimes are found. Participants with high intellectual abilities are less
      motivated to enter substance abuse treatment compared to their counterparts with
      average and low intellectual abilities. Implications for treatment are discussed.

PMID- 15851507
TI  - Methamphetamine use in nonurban and urban drug court clients.
AB  - Population-based surveys suggest that methamphetamine use and abuse may be rising
      in the United States. However, little is known about methamphetamine use in
      eastern sections of the United States, particularly nonurban areas. The purpose
      of the present study was (a) to explore reported methamphetamine use and its
      correlates among Kentucky drug court clients and(b) to determine whether
      differences exist between methamphetamine users by drug court location. Of the
      500 drug court clients surveyed, approximately 32% n=161) reported lifetime
      methamphetamine use. Methamphetamine users and nonusers differed in their drug
      use profiles, self-reported criminal history, and number of criminal offenses.
      Nonurban and urban methamphetamine users differed in their drug-use profiles,
      psychological functioning, self-reported criminal history, and number of criminal
      offenses. These results suggest that differences exist between these populations
      and clinicians, and criminal justice officials may need to consider these
      differences when planning treatment and rehabilitation strategies.

PMID- 15851509
TI  - Loneliness and associated violent antisocial behavior: analysis of the case
      reports of Jeffrey Dahmer and Dennis Nilsen.
AB  - It can be theorized that loneliness plays a significant role in the development
      and continuation of violent, antisocial attitudes and behavior. Analysis of case
      reports of two serial killers, Dennis Nilsen and Jeffrey Dahmer, indicate that
      there is evidence for such a link. In this article, a list of significant
      correlates of loneliness and antisocial behavior is presented. This may be useful
      for the assessment of possible dangerousness and in the development of prevention
      and intervention programs. Suggestions are made for the adequate treatment of
      loneliness and correlated violent, antisocial behavior. A need is recognized for
      more research into the psychosocial, emotional, neurobiological, cultural, and
      ethnic determinants of loneliness and their correlation to specific antisocial
      and/or criminal behavior.

PMID- 15851510
TI  - A plan analysis of pedophile sexual abusers' motivations for treatment: a
      qualitative pilot study.
AB  - Many authors have suggested adapting treatment programs to the specific needs of
      sexual abusers. However, little research has been conducted to understand what
      these patients seek in therapy or what elements play a key role in keeping them
      in treatment. In this pilot study, fifteen (N=15) pedophile sexual abusers from
      La Macaza clinic for sexual abusers were interviewed. Plan analysis was used to
      investigate the most prevalent components involved in staying in or leaving
      therapy. Results suggest that many components involved in the plans leading to
      doing and to avoiding treatment were similar. Differences were found in regards
      to the outcome of confrontations with the therapists, a tendency to isolate and
      overcomply, guilt related to the abuse, a need for a stable environment, and a
      need to be accepted. These results are discussed along with possible ways to
      improve the patients' involvement in treatment.

PMID- 15851511
TI  - Gender differences in life-course theory of recidivism: a survival analysis.
AB  - This study of 300 women and 300 men graduates of a boot camp finds that there are
      noteworthy gender differences in predictors of tenure in the community without
      criminal recidivism in a 5-year follow-up. The Cox proportional hazards models
      show that urban residence, childhood and recent abuses, living with a criminal
      partner, selling drugs, stress, depression, fearfulness, and suicidal thoughts
      are stronger positive predictors of recidivism for women than for men. Men are
      more likely to return to prison because of criminal peer associations, carrying
      weapons, alcohol abuse, and aggressive feelings. Job satisfaction and education
      lengthen time in the community more for men than women, whereas the number of
      children and relationships are more important to tenure in the community for
      women. The implications for the findings for theory are discussed.

PMID- 15851512
TI  - Gambling among offenders: results from an Australian survey.
AB  - This article outlines the results of a recent Australian survey of gambling,
      problem gambling, and gambling-related crimes among offenders. The research found
      that 34% of participant offenders had some form of gambling problem. This figure
      is 18 times higher than that found in the general population in the same
      Australian location. Many problem gamblers identified in the survey had not
      sought help for gambling and felt they didn't have a problem or were in control
      of their gambling. In addition, many survey participants said that their gambling
      was not problematic despite some admissions that they had committed gambling
      related crimes. A significant implication of this study follows that offenders
      with gambling problems need to be offered therapeutic services while in the
      correctional system to reduce the prevalence of gambling problems and the
      commission of gambling-related offences.

PMID- 15851513
TI  - Cross-talk between tuberin, calmodulin, and estrogen signaling pathways.
AB  - Lymphangioleiomyomatosis (LAM) is a rare disease that occurs primarily in women
      and has been linked to both estrogen-mediated signaling events and mutations
      associated with the tuberous sclerosis complex 2 gene product tuberin. These two
      observations fostered the hypothesis that tuberin's impact on estrogen-mediated
      signaling might be through a direct interaction with the intracellular receptor
      for estrogen, estrogen receptor alpha (ERalpha). In the study presented here,
      tuberin was shown to co-immunoprecipitate and directly bind ERalpha through a
      domain localized within the carboxyl 73 amino acids of tuberin. This domain had
      previously been shown to serve as a binding domain for the intracellular calcium
      signaling molecule calmodulin (CaM). Competition binding studies identified a
      potential competitive relationship for binding of tuberin by ERalpha and CaM.
      Additionally, tuberin-ERalpha interactions were found to be modulated by the
      presence of tuberin's predominant intracellular binding partner hamartin,
      suggesting that tuberin-hamartin interactions negatively impact the ability of
      tuberin to modulate ERalpha-mediated gene transcription events. Cumulatively,
      data presented here support the hypothesis that interactions between tuberin,
      ERalpha, and CaM may play a critical role in the pathology of LAM disease.

PMID- 15851514
TI  - Disulfide bridge formation between SecY and a translocating polypeptide localizes
      the translocation pore to the center of SecY.
AB  - During their biosynthesis, many proteins pass through the membrane via a
      hydrophilic channel formed by the heterotrimeric Sec61/SecY complex. Whether this
      channel forms at the interface of multiple copies of Sec61/SecY or is intrinsic
      to a monomeric complex, as suggested by the recently solved X-ray structure of
      the Methanococcus jannaschii SecY complex, is a matter of contention. By
      introducing a single cysteine at various positions in Escherichia coli SecY and
      testing its ability to form a disulfide bond with a single cysteine in a
      translocating chain, we provide evidence that translocating polypeptides pass
      through the center of the SecY complex. The strongest cross-links were observed
      with residues that would form a constriction in an hourglass-shaped pore. This
      suggests that the channel makes only limited contact with a translocating
      polypeptide, thus minimizing the energy required for translocation.

PMID- 15851515
TI  - In vitro assembly and GTP hydrolysis by bacterial tubulins BtubA and BtubB.
AB  - Arecent study identified genuine tubulin proteins, BtubA and BtubB, in the
      bacterial genus Prosthecobacter. We have expressed BtubA and BtubB in Escherichia
      coli and studied their in vitro assembly. BtubB by itself formed rings with an
      outer diameter of 35-36 nm in the presence of GTP or GDP. Mixtures of BtubB and
      BtubA formed long protofilament bundles, 4-7 protofilaments wide (20-30
      protofilaments in the three-dimensional bundle). Regardless of the starting
      stoichiometry, the polymers always contained equal concentrations of BtubA and
      BtubB, suggesting that BtubA and B alternate along the protofilament. BtubA
      showed negligible GTP hydrolysis, whereas BtubB hydrolyzed 0.40 mol GTP per min
      per mol BtubB. This GTPase activity increased to 1.37 per min when mixed 1:1 with
      BtubA. A critical concentration of 0.4-1.0 microM was indicated by light
      scattering experiments and extrapolation of GTPase versus concentration, thus
      suggesting a cooperative assembly mechanism.

PMID- 15851516
TI  - Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine
      kinase and promote its interaction with Tie2.
AB  - The Tie1 receptor tyrosine kinase was isolated over a decade ago, but so far no
      ligand has been found to activate this receptor. Here, we have examined the
      potential of angiopoietins, ligands for the related Tie2 receptor, to mediate
      Tie1 activation. We show that a soluble Ang1 chimeric protein, COMP-Ang1,
      stimulates Tie1 phosphorylation in endothelial cells with similar kinetics and
      angiopoietin dose dependence when compared with Tie2. The phosphorylation of
      overexpressed Tie1 was weakly induced by COMP-Ang1 also in transfected cells that
      do not express Tie2. When cotransfected, Tie2 formed heteromeric complexes with
      Tie1, enhanced Tie1 activation, and induced phosphorylation of a kinase-inactive
      Tie1 in a ligand-dependent manner. Tie1 phosphorylation was also induced by
      native Ang1 and Ang4, although less efficiently than with COMP-Ang1. In
      conclusion, we show that Tie1 phosphorylation is induced by multiple angiopoietin
      proteins and that the activation is amplified via Tie2. These results should be
      important in dissecting the signal transduction pathways and biological functions
      of Tie1.

PMID- 15851517
TI  - Deep-etch EM reveals that the early poxvirus envelope is a single membrane
      bilayer stabilized by a geodetic "honeycomb" surface coat.
AB  - Three-dimensional "deep-etch" electron microscopy (DEEM) resolves a longstanding
      controversy concerning poxvirus morphogenesis. By avoiding fixative-induced
      membrane distortions that confounded earlier studies, DEEM shows that the primary
      poxvirus envelope is a single membrane bilayer coated on its external surface by
      a continuous honeycomb lattice. Freeze fracture of quick-frozen poxvirus-infected
      cells further shows that there is only one fracture plane through this primary
      envelope, confirming that it consists of a single lipid bilayer. DEEM also
      illustrates that the honeycomb coating on this envelope is completely replaced by
      a different paracrystalline coat as the poxvirus matures. Correlative thin
      section images of infected cells freeze substituted after quick-freezing, plus
      DEEM imaging of Tokuyasu-type cryo-thin sections of infected cells (a new
      application introduced here) all indicate that the honeycomb network on immature
      poxvirus virions is sufficiently continuous and organized, and tightly associated
      with the envelope throughout development, to explain how its single lipid bilayer
      could remain stable in the cytoplasm even before it closes into a complete
      sphere.

PMID- 15851518
TI  - A developmentally regulated Na-H exchanger in Dictyostelium discoideum is
      necessary for cell polarity during chemotaxis.
AB  - Increased intracellular H(+) efflux is speculated to be an evolutionarily
      conserved mechanism necessary for rapid assembly of cytoskeletal filaments and
      for morphological polarity during cell motility. In Dictyostelium discoideum,
      increased intracellular pH through undefined transport mechanisms plays a key
      role in directed cell movement. We report that a developmentally regulated Na-H
      exchanger in Dictyostelium discoideum (DdNHE1) localizes to the leading edge of
      polarized cells and is necessary for intracellular pH homeostasis and for
      efficient chemotaxis. Starved DdNHE1-null cells (Ddnhe1(-)) differentiate, and in
      response to the chemoattractant cAMP they retain directional sensing; however,
      they cannot attain a polarized morphology, but instead extend mislocalized
      pseudopodia around the cell and exhibit decreased velocity. Consistent with
      impaired polarity, in response to chemoattractant, Ddnhe1(-) cells lack a leading
      edge localization of F-actin and have significantly attenuated de novo F-actin
      polymerization but increased abundance of membrane-associated
      phosphatidylinositol 3,4,5-trisphosphate (PI((3,4,5))P(3)). These findings
      indicate that during chemotaxis DdNHE1 is necessary for establishing the kinetics
      of actin polymerization and PI((3,4,5))P(3) production and for attaining a
      polarized phenotype.

PMID- 15851519
TI  - Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate
      p59fyn and to enhance neurite outgrowth.
AB  - In spite of advances in understanding the role of the cellular prion protein
      (PrP) in neural cell interactions, the mechanisms of PrP function remain poorly
      characterized. We show that PrP interacts directly with the neural cell adhesion
      molecule (NCAM) and associates with NCAM at the neuronal cell surface. Both cis
      and trans interactions between NCAM at the neuronal surface and PrP promote
      recruitment of NCAM to lipid rafts and thereby regulate activation of fyn kinase,
      an enzyme involved in NCAM-mediated signaling. Cis and trans interactions between
      NCAM and PrP promote neurite outgrowth. When these interactions are disrupted in
      NCAM-deficient and PrP-deficient neurons or by PrP antibodies, NCAM/PrP-dependent
      neurite outgrowth is arrested, indicating that PrP is involved in nervous system
      development cooperating with NCAM as a signaling receptor.

PMID- 15851521
TI  - B cells in rheumatology--transforming thinking in rheumatoid arthritis.

PMID- 15851522
TI  - B cells as a therapeutic target in autoimmune diseases other than rheumatoid
      arthritis.
AB  - Selective B-cell depletion with anti-CD20 therapy is a promising novel treatment
      option for patients with refractory autoimmune disease. The anti-CD20 antibody,
      rituximab, is the first therapeutic monoclonal antibody to have been approved by
      the European Medical Agency (EMEA) and the US Food and Drug Administration (FDA)
      for the treatment of relapsed, low-grade, follicular non-Hodgkin's lymphoma.
      Rituximab is now being studied in a range of autoimmune diseases, most notably
      rheumatoid arthritis, but also chronic immune thrombocytopenic purpura and
      systemic lupus erythematosus. Current data obtained from studies of rituximab
      single-agent therapy for autoimmune disease show good tolerability and sustained
      improvement in disease symptoms, although the precise mechanisms of action in
      autoimmunity remain to be fully clarified. Future research is likely to be
      focused on the optimization of responses with rituximab-based therapy. However,
      early observations suggest that this approach is likely to yield significant
      clinical benefits in a wide range of organ-specific and systemic autoimmune
      diseases.

PMID- 15851523
TI  - Panel discussion on B cells and rituximab: mechanistic aspects, efficacy and
      safety in rheumatoid arthritis and non-Hodgkin's lymphoma.
AB  - The clinical potential of rituximab (MabThera/Rituxan), a selective B-cell
      depleting agent, in the treatment of patients with rheumatoid arthritis (RA) is
      rapidly becoming apparent. The data presented at an official satellite symposium
      of the European League Against Rheumatism (EULAR) Congress (2003, Lisbon,
      Portugal), reinforce the rationale for the use of this novel agent in RA and have
      provided an early indication of its clinical efficacy, safety and tolerability.
      The symposium presentations were followed by a panel discussion and a question
      and answer session in which the participants were able to shed further light on
      specific mechanistic issues relating to effects on B-cell populations based on
      available data and their own clinical experience of rituximab. Additionally, the
      implications of current results for longer-term clinical efficacy and safety were
      discussed. It is becoming clear that rituximab (alone or in combination with
      disease-modifying anti-rheumatic drugs) is highly efficacious in RA. Extensive
      data from patients with non-Hodgkin's lymphoma show that early concerns over
      increased infection rates due to prolonged suppression of B cells have not been
      realized. The effects of rituximab on long-term RA outcomes, such as joint
      erosion and duration of response (particularly in patients receiving combination
      therapy), are eagerly anticipated.

PMID- 15851520
TI  - LL5beta: a regulator of postsynaptic differentiation identified in a screen for
      synaptically enriched transcripts at the neuromuscular junction.
AB  - In both neurons and muscle fibers, specific mRNAs are concentrated beneath and
      locally translated at synaptic sites. At the skeletal neuromuscular junction, all
      synaptic RNAs identified to date encode synaptic components. Using microarrays,
      we compared RNAs in synapse-rich and -free regions of muscles, thereby
      identifying transcripts that are enriched near synapses and that encode soluble
      membrane and nuclear proteins. One gene product, LL5beta, binds to both
      phosphoinositides and a cytoskeletal protein, filamin, one form of which is
      concentrated at synaptic sites. LL5beta is itself associated with the cytoplasmic
      face of the postsynaptic membrane; its highest levels border regions of highest
      acetylcholine receptor (AChR) density, which suggests a role in "corraling"
      AChRs. Consistent with this idea, perturbing LL5beta expression in myotubes
      inhibits AChR aggregation. Thus, a strategy designed to identify novel synaptic
      components led to identification of a protein required for assembly of the
      postsynaptic apparatus.

PMID- 15851524
TI  - B cells: a fundamental role in the pathogenesis of rheumatoid arthritis?
AB  - The role of T cells in the pathogenesis of RA is well established, whereas to
      date the precise contribution of B cells is less well defined. B cells have many
      potential key roles: they can act as antigen-presenting cells, secrete pro
      inflammatory cytokines (including tumour necrosis factor-alpha), produce
      rheumatoid factor (RF) and other autoantibodies and activate T cells. B cells act
      as antigen-presenting cells by processing and presenting antigenic peptides to T
      cells, which become activated, proliferate and exert pro-inflammatory activities.
      RF may also play a role in perpetuating B-cell activation and antigen
      presentation to T cells, thus leading to sustained production of RF. This,
      combined with RF immune-complex-mediated complement activation, may contribute to
      the sustained inflammatory response. Studies have shown that the use of an anti
      CD20 monoclonal antibody in RA depletes circulating B cells, resulting in
      improvement in disease activity for up to 1 yr. It is thus evident that B cells
      play a central role in the pathophysiology of RA and therefore merit further
      investigation as a therapeutic target.

PMID- 15851525
TI  - B cells in rheumatoid arthritis: from hypothesis to the clinic.
AB  - Rituximab (MabThera/Rituxan) is a therapeutic monoclonal antibody against CD20,
      an antigen expressed by B cells but not B-cell progenitor or plasma cells. It is
      currently approved for the treatment of relapsed or refractory B-cell non
      Hodgkin's lymphoma (NHL) and is well tolerated and efficacious. A small open
      label study (conducted by Edwards and Cambridge) indicated that selective
      depletion of B cells using rituximab led to sustained benefits for patients with
      active rheumatoid arthritis. A 24-week, double-blind, randomized controlled trial
      was carried out to confirm these initial observations. In total, 161 patients
      with active rheumatoid arthritis were randomized to one of four treatment groups:
      rituximab monotherapy; rituximab plus methotrexate (R+MTX); rituximab plus
      cyclophosphamide (R+CTX); or methotrexate alone (MTX). Rituximab was administered
      as two 1000 mg infusions on days 1 and 15. An analysis at 24 weeks showed that
      the proportion of patients achieving an ACR20 response was significantly greater
      (P < or = 0.025 for all three comparisons) in all the rituximab groups compared
      with the MTX control group (rituximab alone, 65%; R+CTX, 76%; R+MTX, 73%; MTX
      alone, 38%). Both ACR50 (43 vs 13%; P = 0.005) and ACR70 (23 vs 5%; P = 0.048)
      responses were also significantly higher for the R+MTX group compared with the
      MTX group. The rituximab groups showed no significant safety differences compared
      with the MTX arm. The majority of adverse events were of mild to moderate
      intensity. Rituximab is a novel targeted therapy for the treatment of rheumatoid
      arthritis and it appears to be highly effective, safe and well tolerated.

PMID- 15851526
TI  - SREBP-1 as a transcriptional integrator of circadian and nutritional cues in the
      liver.
AB  - The act of feeding in mammals can generate such powerful cues for peripheral
      organs that, under certain conditions, they can override the entraining signals
      coming from the clock in the brain. Restricting the feeding time to the
      inactivity period, for example, can completely and quickly reverse the rhythms of
      gene expression in the liver. This manipulation does not affect the central
      oscillator in the suprachiasmatic nucleus, which is phase-locked to the light
      dark cycle, but does release the peripheral oscillations in the liver from
      central control. It seems reasonable to predict the existence of one or more
      immediate response systems designed to sense the need to acutely reverse the
      sequence of absorptive and postabsorptive phases in the liver. In this study, the
      authors monitored the posttranslational activation of the sterol response element
      binding proteins from a circadian point of view to evaluate the role they might
      play in the circadian organization of the liver transcriptome as well as in the
      reversal of hepatic physiology that accompanies diurnal restricted feeding. This
      study highlights a possible direct link between the immediate effects of food
      consumption on the level of key membrane and humoral factors and the expression
      status of a set of coordinately regulated target genes in the liver.

PMID- 15851527
TI  - Analysis of the prokineticin 2 system in a diurnal rodent, the unstriped Nile
      grass rat (Arvicanthis niloticus).
AB  - Prokineticin 2 (PK2) is a putative output molecule from the SCN. PK2 RNA levels
      are rhythmic in the mouse SCN, with high levels during the day, and PK2
      administration suppresses nocturnal locomotor activity in rats. The authors
      examined the PK2 system in a diurnal rodent, Arvicanthis niloticus, to determine
      whether PK2 or PK2 receptors differ between diurnal and nocturnal species. The
      major transcript variant of A. niloticus PK2 (AnPK2) encodes a 26-residue signal
      peptide followed by the presumed mature peptide of 81 residues. Within the grass
      rat signal sequence, polymorphic sequences and amino acid substitutions were
      observed relative to mouse and laboratory rats, but the hydrophobic core and
      cleavage site of the signal sequence were preserved. The mature PK2 peptide is
      identical among A. niloticus, rat, and mouse. AnPK2 mRNA is rhythmically
      expressed in the SCN, with peak RNA levels occurring in the morning, preceding
      peaks of Per1 and Per2 as in mouse SCN. Analysis of prokineticin receptor 2
      (PKR2) sequences revealed polymorphisms among the grass rats studied. PKR2 mRNA
      was expressed in the SCN and paraventricular nuclei of the thalamus and
      hypothalamus. While further analysis is necessary, there is no clear evidence
      indicating that a difference in the PK2 ligand/receptor system accounts for
      diurnality in this rodent species. These data contribute to a growing body of
      evidence suggesting that the key to diurnality lies downstream of the SCN in A.
      niloticus.

PMID- 15851528
TI  - Circadian rhythms in mouse blood coagulation.
AB  - The circadian clock, influencing many biological processes, has been demonstrated
      to modulate levels of specific coagulation factors, but its impact on the
      coagulation efficiency is unknown. In a mouse model, the authors evaluated the
      temporal variations in the initial rate of activated factor X (FXa) and thrombin
      generation. Upon coagulation activation through the FVIIa-TF pathway (extrinsic
      activation), both parameters showed rhythmic variations with a significant peak
      at ZT 12, the light-to-dark transition. In mice subjected to a 6-h delayed light
      dark cycle, the peak was shifted as expected. These cyclic oscillations were also
      observed in constant darkness, thus demonstrating, for the first time, the
      existence of strong circadian rhythms of the initial rate of either FXa or
      thrombin generation activity levels. These circadian variations overlapped with
      those that have been recently described in factor VII (FVII) activity. The peak
      of FXa generation activity was simulated by the addition of purified human FVII,
      thus indicating that circadian variations in FVII activity are important
      determinants of the circadian rhythm of the procoagulant cascade efficiency.
      These findings help to elucidate the complex control on the coagulation process
      and might contribute in explaining the temporal variations in the frequency of
      cardiovascular events observed in humans.

PMID- 15851530
TI  - Drosophila olfactory response rhythms require clock genes but not pigment
      dispersing factor or lateral neurons.
AB  - Odors elicit a number of behavioral responses, including attraction and repulsion
      in Drosophila. In this study, the authors used a T-maze apparatus to show that
      wild-type Drosophila melanogaster exhibit a robust circadian rhythm in the
      olfactory attractive and repulsive responses. These responses were lower during
      the day and began to rise at early night, peaking at about the middle of the
      night and then declining thereafter. They were also independent of locomotor
      activity. The olfactory response rhythms were lost in period or timeless mutant
      flies (per0, tim0), indicating that clock genes control circadian rhythms of
      olfactory behavior. The rhythms in olfactory response persisted in the absence of
      the pigment-dispersing factor neuropeptide or the central pacemaker lateral
      neurons known to drive circadian patterns of locomotion and eclosion. These
      results indicate that the circadian rhythms in olfactory behavior in Drosophila
      are driven by pacemakers that do not control the rest-activity cycle and are
      likely in the antennae.

PMID- 15851529
TI  - Circadian regulation of hippocampal long-term potentiation.
AB  - The goal of this study is to investigate the possible circadian regulation of
      hippocampal excitability and long-term potentiation (LTP) measured by stimulating
      the Schaffer collaterals (SC) and recording the field excitatory postsynaptic
      potential (fEPSP) from the CA1 dendritic layer or the population spike (PS) from
      the soma in brain slices of C3H and C57 mice. These 2 strains of mice were of
      interest because the C3H mice secrete melatonin rhythmically while the C57 mice
      do not. The authors found that the magnitude of the enhancement of the PS was
      significantly greater in LTP recorded from night slices compared to day slices of
      both C3H and C57 mice. They also found significant diurnal variation in the decay
      of LTP measured with fEPSPs, with the decay slower during the night in both
      strains of mice. There was evidence for a diurnal rhythm in the input/output
      function of pyramidal neurons measured at the soma in C57 but not C3H mice.
      Furthermore, LTP in the PS, measured in slices prepared during the day but
      recorded during the night, had a profile remarkably similar to the night group.
      Finally, PS recordings were carried out in slices from C3H mice maintained in
      constant darkness prior to experimentation. Again, the authors found that the
      magnitude of the enhancement of the PS was significantly greater in LTP recorded
      from subjective night slices compared to subjective day slices. These results
      provide the 1st evidence that an endogenous circadian oscillator modulates
      synaptic plasticity in the hippocampus.

PMID- 15851531
TI  - Restraint stress delays reentrainment in male and female diurnal and nocturnal
      rodents.
AB  - A temporary loss of normal circadian entrainment, such as that associated with
      shift work and transmeridian travel, can result in an array of detrimental
      symptoms, making rapid reentrainment of rhythmicity essential. While there is a
      wealth of literature examining the effects of stress on the entrained circadian
      system, less is known about the influence of stress on circadian function
      following a phase shift of the light: dark (LD) cycle. The authors find that
      recovery of locomotor activity synchronization is altered by restraint stress in
      the diurnal rodent Octodon degus (degu) and the nocturnal rat. In the first
      experiment, degus were subjected to a 6-h phase advance of the LD cycle. Sixty
      minutes after the new lights-on, animals underwent 60 min of restraint stress.
      The number of days it took each animal to reentrain its activity rhythms to the
      new LD cycle was recorded and compared to the number of days it took the animal
      to reentrain under control conditions. When subjected to restraint stress, degus
      took 30% longer to reentrain their activity rhythms (p < 0.01). In a second
      experiment, rats underwent a similar experimental paradigm. As with the degus,
      stress significantly delayed the reentrainment of rats' activity rhythms (p <
      0.01). There was no interaction between sex and stress on the rate of
      reentrainment for either rats or degus. Furthermore, there was no effect of
      stress on the free-running activity rhythm of degus, suggesting that the effect
      of stress on reentrainment rate is not secondary to alterations of period length.
      Together, these data point to a detrimental effect of stress on recovery of
      entrainment of circadian rhythms, which is independent of activity niche and sex.

PMID- 15851532
TI  - Synchronizing genetic oscillators by signaling molecules.
AB  - The authors examine collective rhythms in a general multicell system with both
      linearly diffusive and nondiffusive couplings. The effect of coupling on
      synchronization through intercellular signaling in a population of Escherichia
      coli cells is studied. In particular, a synchronization solution is given through
      the auxiliary individual system for 2 types of couplings. The sufficient
      conditions for the global synchronization of such a coupled system are derived
      based on the Lyapunov function method. The authors show that an appropriate
      design of the coupling and the inner-linking matrix can ensure global
      synchronization of the coupled synthetic biological system. Moreover, they
      demonstrate that the dynamics of an individual cell with coupling and without
      coupling may be qualitatively different; one is oscillatory, and the other is
      steady state. The change from a nonoscillatory state to an oscillatory one is
      induced by appropriate coupling, which also entrains all cells to
      synchronization. These results establish not only a theoretical foundation but
      also a quantitative basis for understanding the essential cooperative dynamics,
      such as collective rhythms or synchronization, in a population of cells.

PMID- 15851533
TI  - Short-wavelength sensitivity of the human circadian system to phase-advancing
      light.

PMID- 15851534
TI  - Adult female victims of child sexual abuse: multitype maltreatment and disclosure
      characteristics related to subjective health.
AB  - This study examined the impact of child sexual abuse and disclosure
      characteristics on adult psychological and psychosomatic symptoms. Data on abuse
      characteristics, disclosure-related events, and subjective health were collected
      through semistructured interviews and questionnaires from 123 adult women
      reporting having been sexually abused in childhood by someone close. The results
      indicate that disclosure-related events have a stronger relation than abuse
      characteristics to long-term consequences of childhood sexual abuse. In
      particular, a positive reaction from a partner was related to fewer symptoms. Of
      the abuse characteristics, exposure also to physical abuse was strongly
      associated to psychological sequelae.

PMID- 15851535
TI  - Examining the characteristics of male sexual assault targets in a Southern
      maximum-security prison.
AB  - Studies concerning inmate-on-inmate sexual assaults within male correctional
      facilities are sparse in the sociological and correctional literatures. Only a
      few studies have specifically examined the characteristics of male inmate sexual
      assault targets. The current research sought to address this gap by providing an
      examination of factors related to victimization likelihood. Using data gathered
      in March 2000 from 142 inmates (18% return rate) in one Southern maximum-security
      prison, the authors examined demographic and behavioral characteristics of male
      inmate sexual targets. Based on inmates' self-reports of sexual victimization-
      threatened and/or forced sexual assault encounters--correlates of victimization
      were identified. Approximately 18% of the inmates reported inmate-on-inmate
      sexual threats, and 8.5% reported that they had been sexually assaulted by
      another inmate while incarcerated.

PMID- 15851536
TI  - Attitudes toward sex and sex offences among Israeli and former Union of Soviet
      Socialist Republic youth: implication for prevention strategies for new
      immigrants.
AB  - The phenomenon of sex offences among new immigrants from the former USSR is a
      source of concern in Israel. This research studied students from Israel (n = 257)
      and the Ukraine (n = 195) to learn about their system of social norms and values
      regarding sex and sex offences. For the purposes of this study, a new tool was
      structured and validated that examines attitudes toward 11 spheres of life
      connected with the research topic, such as the status of men and the victim's
      responsibility for rape. The principal findings show significant differences in
      the norms and values of the surveyed groups, reflecting negative norms among
      Ukrainian youth. Results are examined in light of the possible implications for
      understanding the phenomenon of sexual violence among immigrant youth from the
      former USSR and the appropriate methods for treating them in Israel. The
      discussion highlights possible implications for other countries that face similar
      issues.

PMID- 15851537
TI  - A friend in need: the role of friendship quality as a protective factor in peer
      victimization and bullying.
AB  - This study examined friendship quality as a possible moderator of risk factors in
      predicting peer victimization and bullying. Children (50 boys and 49 girls, ages
      10 to 13 years) reported on the quality of their best friendship, as well as
      their bullying and victimization tendencies. Parents reported on their child's
      internalizing and externalizing behaviors, in addition to bullying and
      victimization tendencies. Results indicated that externalizing problems were
      related to bullying behavior; however, friendship quality moderated this relation
      such that among children with externalizing behaviors, a high-quality friendship
      significantly attenuated bullying behavior. Internalizing problems and low
      friendship quality were significantly related to victimization; however,
      friendship quality did not moderate the relation between internalizing problems
      and victimization. Implications for interventions based on these findings are
      discussed.

PMID- 15851538
TI  - Rates and predictors of sexual aggression among students and non-students.
AB  - The authors compared rates and predictors of sexual aggression for women
      attending college with those of women from the same population who were not
      attending college. Because it has been suggested that less parental monitoring at
      college may be associated with risky behaviors that contribute to sexual
      aggression, they also compared rates and predictors of sexual aggression for
      those living with parents versus not living with parents. The results showed that
      women living away from parents reported significantly higher rates of sexual
      aggression than women living with parents, regardless of student status. Logistic
      regression analyses showed that for student and non-student women, heavy episodic
      drinking and number of sex partners predicted past-year rape and/or attempted
      rape. The current results do not provide evidence that college is a uniquely
      risky environment for experiencing sexual aggression. Rather, the behaviors in
      which young women engage are associated with sexual aggression during this time
      period.

PMID- 15851539
TI  - Attitudes toward victims of rape: effects of gender, race, religion, and social
      class.
AB  - Although previous literature focusing on perceptions of victims of rape has
      examined how gender, race, and culture influence the attitudes one holds toward
      victims, these studies have yielded mixed results. This study compared
      perceptions of victims of rape across a wide range of ages, educational
      backgrounds, religions, and income levels, while focusing on gender and racial
      differences. Results indicate (N = 220) that victims of rape are generally viewed
      more sympathetically by females than by males and by Whites than by African
      Americans. However, the effect of race disappears when socioeconomic variables
      are controlled, suggesting a more complex relationship. Also, a hierarchical
      regression indicates that age, sex, education, and income are significant
      predictors of attitudes toward victims. This study builds on existing research
      that examines such attitudes from a cultural perspective and extends this
      literature by examining the interactive effects of several demographic variables
      within a community sample.

PMID- 15851540
TI  - Self-defense or assertiveness training and women's responses to sexual attacks.
AB  - Self-defense classes aim to prevent violence against women by strengthening
      women's capacity to defend themselves; however, little research has examined the
      effects of self-defense training on women's attempts to fight back during actual
      attacks. This study investigated the relationship of self-defense or
      assertiveness training and women's physical and psychological responses to
      subsequent rape attacks (N = 1,623). Multivariate analyses showed that victims
      with preassault training were more likely to say that their resistance stopped
      the offender or made him less aggressive than victims without training. Women
      with training before their assaults were angrier and less scared during the
      incident than women without training, consistent with the teachings of self
      defense training. Preassault training participants rated their degree of non
      consent or resistance as lower than did nonparticipants, perhaps because they
      held themselves to a higher standard. Suggestions for future research on women's
      self-defense training and rape prevention are offered.

PMID- 15851541
TI  - Public health advocacy to change corporate practices: implications for health
      education practice and research.
AB  - Corporate practices, such as advertising, public relations, lobbying, litigation,
      and sponsoring scientific research, have a significant impact on the health of
      the people in the United States. Recently, health professionals and advocates
      have created a new scope of practice that aims to modify corporate practices that
      harm health. This article describes how corporate policies influence health and
      reviews recent health campaigns aimed at changing corporate behavior in six
      industries selected for their central role in the U.S. economy and their
      influence on major causes of mortality and morbidity. These are the alcohol,
      automobile, food, gun, pharmaceutical, and tobacco industries. The article
      defines corporate disease promotion and illustrates the range of public health
      activities that have emerged to counter such corporate behaviors. It analyzes the
      role of health professionals, government, and advocacy groups in these campaigns
      and assesses the implications of this domain for health education practice and
      research.

PMID- 15851542
TI  - More than a message: framing public health advocacy to change corporate
      practices.
AB  - Framing battles in public health illustrate the tension in our society between
      individual freedom and collective responsibility. This article describes how two
      frames, market justice and social justice, first articulated in a public health
      context by Dan Beauchamp, influence public dialogue on the health consequences of
      corporate practices. The authors argue that public health advocates must
      articulate the social justice values motivating the changes they seek in specific
      policy battles that will be debated in the context of news coverage. The authors
      conclude with lessons for health education practitioners who need to frame public
      health issues in contentious and controversial policy contexts. Specific lessons
      include the importance of understanding the existing values and beliefs
      motivating the public health change being sought, the benefits of articulating
      core messages that correspond to shared values, and the necessity of developing
      media skills to compete effectively with adversaries in public debate.

PMID- 15851543
TI  - Collective actors and corporate targets in tobacco control: a cross-national
      comparison.
AB  - Cross-national comparative analysis of tobacco control strategies can alert
      health advocates to how opportunities for public health action, types of action,
      and probabilities for success are shaped by political systems and cultures. This
      article is based on case studies of tobacco control in the United States, Canada,
      Britain, and France. Two questions are addressed: (a) To whom were the dangers of
      smoking attributed? and (b) What was the role of collective action--grassroots
      level organization--in combating these dangers? Activists in Canada, Britain, and
      France moved earlier than the United States did to target the tobacco industry
      and the state. Locally based advocacy centered on passive smoking has been far
      more important in the United States. The author concludes that U.S.-style
      advocacy has played a major role in this country's smoking decline but is
      insufficient in and of itself to change the corporate practices of a wealthy and
      politically powerful industry.

PMID- 15851544
TI  - Indian youth speak about tobacco: results of focus group discussions with school
      students.
AB  - This article discusses the findings of Focus Group Discussions (FGDs) that were
      conducted as a formative assessment for Project MYTRI (Mobilizing Youth for
      Tobacco Related Initiatives in India), a randomized, multicomponent, school-based
      trial to prevent and control tobacco use among youth in India. Forty-eight FGDs
      were conducted with students (N=435) in sixth and eighth grades in six schools in
      Delhi, India. Key findings include: (a) students in government schools reported
      as "consumers" of tobacco, whereas students in private schools reported as
      "commentators"; (b) parents and peers have a strong influence on youth tobacco
      use; (c) chewing gutkha is considered less harmful and more accessible than
      smoking cigarettes; (d) schools are not promoting tobacco control activities; and
      (e) students were enthusiastic about the role government should play in tobacco
      control. These findings are being used to develop a comprehensive intervention
      program to prevent and control tobacco use among Indian youth.

PMID- 15851545
TI  - Relationships among youth assets and neighborhood and community resources.
AB  - Recent research suggests that a youth development framework emphasizing youth
      assets may be a promising intervention strategy for preventing adolescent risk
      behaviors. Understanding how neighborhood and community resources relate to youth
      assets may aid in identifying environmental strategies to complement individually
      oriented asset-building interventions. In this study, 1,350 randomly selected
      inner-city youth and their parents (paired interviews) were interviewed in
      person. After controlling for demographic characteristics of youth and parents
      using multivariate logistic regression, parental perception of neighborhood
      safety was associated with the nonparental adult role model asset, peer role
      model asset, and for African American youth, the community involvement asset.
      City services and neighborhood services were associated with use of time
      (groups/sports) and use of time (religion), respectively. Psychological sense of
      community was associated with community involvement for Native American youth.
      Findings suggest that neighborhood and community-level influences should be
      considered when designing youth development interventions to reduce risk
      behaviors.

PMID- 15851546
TI  - Assessing the perceived importance of skin cancer: how question-order effects are
      influenced by issue involvement.
AB  - Question-order effects refer to systematic differences in responses that can be
      attributed to the manner in which questions assessing attitudes and cognitions
      are asked. This article hypothesized that question-order effects in assessing the
      perceived importance of skin cancer would be moderated by the extent to which
      people are involved with the issue of skin cancer. A telephone survey (N=325) was
      conducted by administering two versions of the same questionnaire, one in which
      importance of skin cancer was assessed without other contextual variables and
      another in which contextual variables were asked before assessing the importance
      of skin cancer. As hypothesized, when people were highly involved with the issue,
      question-order effects did not occur. When involvement was low, importance of
      skin cancer was greater in the absence of contextual questions than in their
      presence. Findings have implications for how health-related issues are
      communicated to the public and how formative research is conducted.

PMID- 15851547
TI  - Self-esteem and theoretical mediators of safer sex among African American female
      adolescents: implications for sexual risk reduction interventions.
AB  - Theories of health behavior posit that change is accomplished by modifying
      factors deemed as mediators. A set of mediators from several theoretical models
      used in sexual risk reduction programs was assessed among a sample of 522 African
      American female adolescents. The goal was to determine whether self-esteem was
      associated with sexually transmitted disease (STD), pregnancy, and the set of
      theoretical mediators controlling for covariates. Bivariate analyses showed no
      relationship between self-esteem and STD or pregnancy; multivariate regression
      analysis revealed a significant relation between self-esteem and the set of
      mediators. Girls higher in self-esteem were more likely to hold positive condom
      attitudes, felt more efficacious in negotiating condom use, had more frequent
      communication with sex partners and parents, perceived fewer barriers to using
      condoms, and were less fearful of negotiating condom use. Self-esteem should be
      considered when designing and evaluating sexual risk reduction programs for this
      population.

PMID- 15851548
TI  - IOVS statement on "double publication".

PMID- 15851549
TI  - Persistent hyperplastic primary vitreous in transgenic mice expressing IE180 of
      the pseudorabies virus.
AB  - PURPOSE: Pseudorabies virus (PRV), a representative member of the alpha
      herpesvirus family, causes nervous symptoms and ocular lesions, such as
      keratoconjunctivitis and retinal degeneration in piglets. The immediate-early
      protein IE180 of the PRV is known to be essential, not only in viral gene
      expression, but also in the cellular gene expression in host cells. The purpose
      of this study was to examine the effect of IE180 on the development of the mouse
      eye, by using transgenic technology. METHODS: Transgenic mice expressing IE180
      were generated and their eyes analyzed by histology, immunocytochemistry, and the
      bromodeoxyuridine cell proliferation assay. RESULTS: A fibrovascular retrolental
      tissue analogous to persistent hyperplastic primary vitreous (PHPV) in humans was
      observed in a transgenic mouse line expressing IE180. The gross anatomy of the
      eye showed white pupils. Analysis of hematoxylin and eosin-stained sections
      revealed that the retrolental tissue adhered to the neuroretina, the inner
      nuclear and ganglion cell layers were disorganized, and rosettelike arrangements
      of dysplastic photoreceptor cells were present. Bromodeoxyuridine-positive cells
      were detected in the retrolental tissues of postnatal day (P)1, P7, and P14 mice.
      The retrolental mass in the P7 transgenic mouse was composed of melanocytes and
      endothelial cells, which were detected by a cocktail of antibodies against
      endoglin, CD31, and VEGF receptor-2. CONCLUSIONS: The observation that the eye
      disease in transgenic mice is similar to that in PHPV in humans raises the
      possibility that expression of the immediate-early gene of alpha-herpesviruses
      may contribute to PHPV.

PMID- 15851550
TI  - Experimental percutaneous cannulation of the supraorbital arteries: implication
      for future therapy.
AB  - PURPOSE: There is some evidence to suggest that thrombolysis has a beneficial
      effect in retinal vessel occlusion. However, there is concern that this
      therapeutic approach carries the risk of hemorrhage. Retrograde cannulation of
      the supraorbital arteries followed by irrigation with fibrinolytic agents may
      have the potential to minimize the risk of major complications. The study was
      conducted to investigate the anatomic and sonographic features of the
      supraorbital arteries. METHODS: This cadaver dissection study was performed on
      the orbits of 12 cadaveric specimens. In each orbit, the supraorbital region was
      dissected, followed by cannulation of the supraorbital vessels and injection of
      ink. In six orbits, the orbital vessels and the distribution of the injected ink
      were investigated. Continuous-wave Doppler sonographic analysis of the
      supratrochlear and the supraorbital artery was performed in 40 orbits of 20
      volunteers to measure the distance between the arteries and the midline. RESULTS:
      Cannulation with retrograde injection of ink was successfully performed in both
      the supratrochlear and the supraorbital arteries. The supratrochlear artery
      exhibited a more superficial course and a larger diameter than the supraorbital
      artery (1.08 +/- 0.19 mm vs. 0.86 +/- 0.19 mm [SD]). Dissection to the orbital
      apex revealed a spread of ink into the ophthalmic and the central retinal
      arteries. The average distance between the exit of the supratrochlear artery and
      the midline was found to be 16.4 +/- 1.7 mm (range, 13-20). The average distance
      between the exit of the supraorbital artery and the midline measured 26.5 +/- 2.6
      mm (range, 23-35). CONCLUSIONS: The findings of this anatomic and sonographic
      study support the concept of percutaneous supraorbital vessel cannulation as a
      potential approach to thrombolysis in retinal vessel occlusion. The
      supratrochlear artery appears to provide the most reliable access route.

PMID- 15851551
TI  - Functional analysis of the p53 pathway in response to ionizing radiation in uveal
      melanoma.
AB  - PURPOSE: Uveal melanomas are notoriously radioresistant and thus necessitate
      treatment with extremely high radiation doses that often cause ocular
      complications. The p53 tumor suppressor pathway is a major mediator of the
      cellular response to radiation-induced DNA damage, suggesting that this pathway
      may be defective in uveal melanoma. The current study was conducted to analyze
      the functional integrity of the p53 pathway in primary uveal melanoma cells.
      METHODS: The p53 gene was sequenced in three primary uveal melanoma cells lines.
      Cultured primary uveal melanoma cells (MM28, MM50, Mel202, Mel270, and Mel290),
      MCF7 breast carcinoma cells, normal uveal melanocytes (UM47), and normal human
      diploid fibroblasts (NHDFs) were irradiated at 250 kVp and 12 mA at a dose rate
      of 1.08 Gy/min for a total dose of up to 20 Gy. Cell viability was analyzed with
      trypan blue exclusion. Western blot analysis was used to analyze the expression
      of p53, p53-phospho-Ser15, p21, Bax, PUMA, and Bcl-x(L). RESULTS: No p53 gene
      mutations were found in MM28, MM50, or Mel270 cells. Upstream signaling to p53
      was intact, with normal induction of p53 and phosphorylation of p53-Ser15, in all
      five cell lines. Radiation-induced downstream activation of p21 was defective in
      MM28 and MM50 cells, and activation of Bax was defective in MM50 and Mel290
      cells. MM28, MM50, and Mel202 cells failed to deamidate Bcl-x(L) in response to
      radiation-induced DNA damage. Overall, four of the five uveal melanoma cell lines
      exhibited at least one downstream defect in the p53 pathway. CONCLUSIONS:
      Expression of p53 and upstream signaling to p53 in response to radiation-induced
      DNA damage appear to be intact in most uveal melanomas. In contrast, functional
      defects in the p53 pathway downstream of p53 activation appear to be common.
      Further elucidation of p53 pathway abnormalities in uveal melanoma may allow
      therapeutic interventions to increase the radiosensitivity of the tumors.

PMID- 15851552
TI  - TNF-857T, a genetic risk marker for acute anterior uveitis.
AB  - PURPOSE: To determine the association between 17 single nucleotide polymorphisms
      (SNPs) of tumor necrosis factor-alpha, lymphotoxin-alpha, and the TNF-receptors
      genes (TNF, LTA, and TNFRSF1A and -B) and idiopathic acute anterior uveitis (IAU)
      and to investigate their association with HLA-B27 and/or the development of
      visually significant complications. METHODS: Ninety-eight white patients in the
      United Kingdom were identified (by SL) from the uveitis clinics of Moorfields Eye
      Hospital (London, UK). Sequence-specific primers with 3' end mismatches were used
      to identify the presence of specific allelic variants by PCR amplification.
      RESULTS: There was a significant increase in the frequency of the TNF-857T allele
      in patients with IAU when compared with control subjects (15.3% vs. 7.3%, P =
      0.0006). The frequency of haplotype 4, containing the T allele at nucleotide
      position -857, was also significantly increased in patients with IAU compared
      with control subjects (15.4% vs. 7.1%, P = 0.0003, OR 2.4, 95% confidence
      interval 1.4-4.0). In subgroup analysis, there were significant differences in
      the frequencies of the uncommon TNFRSF1A-201T and TNFRSF1A-1135T alleles between
      HLA-B27(+) patients with inflammation-related complications and those without
      complications (80.0% vs. 33.6%, P = 0.006; 80.0% vs. 36.6%, P = 0.01,
      respectively). CONCLUSIONS: A significant difference in the frequency of TNF-857T
      allele was found in patients with IAU. There was a trend toward the development
      of inflammation-related complications in HLA-B27(+) patients with IAU who were
      carriers of TNFRSF1A-201T or TNFRSF1A-1135T alleles. Genetic variations in these
      proinflammatory mediators and their receptors appear to influence the
      susceptibility and severity of the inflammatory response within the eyes of
      patients during the development of IAU.

PMID- 15851553
TI  - The lacrimal gland transcriptome is an unusually rich source of rare and poorly
      characterized gene transcripts.
AB  - PURPOSE: To sequence and comprehensively analyze human and mouse lacrimal gland
      transcriptomes as part of the NEIBank project. METHODS: cDNA libraries generated
      from normal human and mouse lacrimal glands were sequenced and analyzed by PHRED,
      RepeatMasker, BLAST, and GRIST. Human "lacrimal-preferred genes" and putative
      gene regulatory elements were respectively identified in UniGene and ConSite, and
      gene clustering was analyzed by chromosomal mapping. "Hypothetical proteins,"
      identified by keyword search, were verified by genomic alignment and queried in
      the Conserved Domain database and GEO Profiles. RESULTS: The top six transcripts
      in human and mouse differed, revealing a previously unappreciated molecular
      divergence. The human transcriptome is enriched with transcripts from 29 lacrimal
      preferred genes and a content of poorly characterized hypothetical proteins,
      proportionally greater than in all other tissues. Only 45% of lacrimal preferred,
      but 71% of hypotheticals, have mouse orthologs. Many of the latter display
      apparently altered cancer expression in the CGAP SAGE library collection-often in
      keeping with predicted WD40, protein kinase, Src homology 2 and 3, RhoGEF, and
      pleckstrin homology domains involved in cell signaling. At the genomic level,
      lacrimal-expressed genes show some evidence of clustering, particularly on human
      chromosomes 9 and 12. Binding sites for TFAP2A, FOXC1, and other transcription
      factors are predicted. CONCLUSIONS: Interspecies divergence cautions against use
      of mouse models of human dry eye syndromes. Lacrimal preferred and hypothetical
      proteins, gene clustering, and putative gene regulatory elements together provide
      new clues for a molecular understanding of lacrimal gland function and mechanisms
      of coordinated tissue-specific transcriptional regulation.

PMID- 15851554
TI  - Whole-body bioluminescent imaging of human uveal melanoma in a new mouse model of
      local tumor growth and metastasis.
AB  - PURPOSE: Human uveal melanoma develops in one of the most capillary-rich tissues
      of the body and has a pure hematogenous dissemination. Radiodiagnostic
      examinations, such as ultrasonic diagnostic resonance imaging and chest
      radiographs plus liver enzyme studies in blood, are methods used to detect liver
      and other distant metastases in patients. Nevertheless, the mortality rate is
      high, because of the frequent occurrence of metastases and the lack of systemic
      therapy. Therefore, the development of novel anticancer strategies is urgent, and
      more sensitive and less invasive methods of detecting and monitoring in vivo
      tumor growth and metastatic disease in cancer models are needed. METHODS: A
      luciferase (Luc)-positive human uveal melanoma cell line (OCM-1 FRT/luc) was
      established. Tumor cells were inoculated into the anterior chamber of murine eyes
      for induction of orthotopic growth or into the left heart ventricle to mimic
      hematogenous micrometastatic spread. Development of metastases and tumor growth
      was monitored weekly by whole-body bioluminescent reporter imaging (BLI).
      RESULTS: Injection of cancer cells into the anterior chamber of the eye of mice
      closely mimicked orthotopic tumor growth of uveal melanoma. Tumor progression
      could be quantitatively monitored 3 weeks after inoculation of 10(5) OCM-1
      FRT/luc cells. Of the mice injected, 83% exhibited a detectable tumor within 5
      weeks. Intracardiac injection of tumor cells resulted in metastatic growth,
      especially in bone. Mice had bone (maxillofacial region and femora) and visceral
      (lung and mediastinum) metastases after 4 to 6 weeks. OCM-1 FRT/luc cells may
      also have a propensity to colonize the eye after intracardiac inoculation.
      CONCLUSIONS: BLI enables continuous quantitative monitoring in the same animal of
      growth kinetics for each tumor and its metastases. This model will accelerate the
      understanding of the pathogenesis and treatment of uveal melanoma and metastasis.

PMID- 15851555
TI  - Heritability of refractive error and familial aggregation of myopia in an elderly
      American population.
AB  - PURPOSE: To determine the heritability of refractive error and the familial
      aggregation of myopia in an older population. METHODS: Seven hundred fifty-nine
      siblings (mean age, 73.4 years) in 241 families were recruited from the Salisbury
      Eye Evaluation (SEE) Study in eastern Maryland. Refractive error was determined
      by noncycloplegic subjective refraction (if presenting distance visual acuity was
      < or =20/40) or lensometry (if best corrected visual acuity was >20/40 with
      spectacles). Participants were considered plano (refractive error of zero) if
      uncorrected visual acuity was >20/40. Preoperative refraction from medical
      records was used for pseudophakic subjects. Heritability of refractive error was
      calculated with multivariate linear regression and was estimated as twice the
      residual between-sibling correlation after adjusting for age, gender, and race.
      Logistic regression models were used to estimate the odds ratio (OR) of myopia,
      given a myopic sibling relative to having a nonmyopic sibling. RESULTS: The
      estimated heritability of refractive error was 61% (95% confidence interval [CI]:
      34%-88%) in this population. The age-, race-, and sex-adjusted ORs of myopia were
      2.65 (95% CI: 1.67-4.19), 2.25 (95% CI: 1.31-3.87), 3.00 (95% CI: 1.56-5.79), and
      2.98 (95% CI: 1.51-5.87) for myopia thresholds of -0.50, -1.00, -1.50, and -2.00
      D, respectively. Neither race nor gender was significantly associated with an
      increased risk of myopia. CONCLUSIONS: Refractive error and myopia are highly
      heritable in this elderly population.

PMID- 15851556
TI  - Association between symptoms and signs of dry eye among an elderly Chinese
      population in Taiwan: the Shihpai Eye Study.
AB  - PURPOSE: To analyze the association between dry-eye symptoms and signs in an
      elderly Chinese population in Taipei, Taiwan. METHODS: The participants were
      those of the Shihpai Eye Study, a population-based survey of eye diseases in the
      elderly (> or =65 years) in Shihpai, Taipei, Taiwan. Of 2045 randomly selected
      noninstitutionalized residents, 1361 (66.6%) participated in the study. Dry-eye
      symptoms were evaluated with an interviewer-administered questionnaire. Dry-eye
      signs, including tear-film breakup time, Schirmer test result, score for
      fluorescein staining of the cornea, and meibomian gland dysfunction, were
      assessed. Correlations between symptoms and signs were analyzed. RESULTS: Of the
      participants, 33.7% (459/1361) were symptomatic, defined as reporting one or more
      symptoms often or all the time. A Schirmer result of < or =5 mm was the only sign
      associated with frequent symptoms (P = 0.028). Its sensitivity and specificity in
      detecting symptomatic subjects were 62.5% and 43.7%, respectively. The agreement
      between each sign was statistically significant, although weak, except that no
      correlation was found between the Schirmer result and meibomian gland anomalies.
      Of the symptomatic subjects, 85.4% (392/459) had either a low Schirmer result or
      a meibomian gland anomaly; 38.8% (178/459) of them were abnormal on both tests.
      CONCLUSIONS: The Schirmer test was shown to be incapable of detecting meibomian
      gland disease. However, a low Schirmer result was significantly associated with
      dry-eye symptoms in this elderly Chinese population. This result differs from
      that of previous reports of elderly white populations. Further studies are needed
      to determine whether this difference indicates racial diversity in the
      distribution and behavior of dry-eye diseases.

PMID- 15851557
TI  - No pathogenic mutations identified in the COL8A2 gene or four positional
      candidate genes in patients with posterior polymorphous corneal dystrophy.
AB  - PURPOSE: To identify the genetic basis of posterior polymorphous corneal
      dystrophy (PPCD) through screening of four positional candidate genes and the
      COL8A2 gene, in which a presumed pathogenic mutation has previously been
      identified in affected patients. METHODS: DNA extraction, PCR amplification, and
      direct sequencing of the COL8A2, BFSP1, CST3, MMP9, and SLPI genes were performed
      in 14 unrelated, affected patients and in unaffected family members. RESULTS: In
      the COL8A2 gene, the previously identified, presumed pathogenic mutation
      (Gln455Lys) was not discovered in any of the affected patients. A missense
      mutation, Thr502Met, was identified in 2 of the 14 affected probands, although it
      was not considered to be pathogenic, as it has been identified in unaffected
      individuals. Although several novel and previously identified single nucleotide
      polymorphisms producing synonymous and missense amino acid substitutions were
      identified in the COL8A2, BFSP1, CST3, MMP9, and SLPI genes, no presumed
      pathogenic sequence variants were found. CONCLUSIONS: No pathogenic mutations
      were identified in the COL8A2 gene or in several positional candidate genes in a
      series of patients with PPCD, indicating that other genetic factors are involved
      in the development of this autosomal dominant corneal dystrophy.

PMID- 15851558
TI  - Detection and quantification of sulfated disaccharides from keratan sulfate and
      chondroitin/dermatan sulfate during chick corneal development by ESI-MS/MS.
AB  - PURPOSE: To identify and quantify changes in keratan sulfate (KS) and
      chondroitin/dermatan sulfate (CS/DS) sulfated disaccharides in the developing
      chick cornea using electrospray ionization tandem mass spectrometry (ESI-MS/MS).
      METHODS: Cryostat sections of fresh nonfixed corneas were obtained from White
      Leghorn embryonic day (E)8 to E20 chicks, and from 4- and 70-week-old chickens.
      Tissue sections on glass slides were incubated with selected glycosidase enzymes.
      Digest solutions were analyzed directly by ESI-MS/MS. RESULTS: The concentration
      of KS monosulfated disaccharide (MSD) Gal-beta-1,4-GlcNAc(6S) in E8 cornea
      equaled that at E20, declined to its lowest level by E10, increased to a second
      peak by E14, decreased to a second low by E18, peaked again by E20, and remained
      high in adult corneas. A similar concentration profile was observed for KS
      disulfated disaccharide (DSD) Gal(6S)-beta-1,4-GlcNAc(6S), and thus also for
      total sulfated KS disaccharides. The molar percent of DSD was higher than that of
      MSD from E8 to E18, equivalent at E20, and less than that of MSD in adult
      corneas. In contrast, total concentration of CS/DS Deltadi-4S plus Deltadi-6S
      decreases as development progresses and is lowest in adult corneas. Concentration
      and molar percent of Deltadi-6S is highest at E8, then decreases through
      development as the concentration and molar percent of Deltadi-4S increases from
      E8 and exceeds that of Deltadi-6S after E14. CONCLUSIONS: New, rapid, direct
      chemical analysis of extracellular matrix components obtained from sections from
      embryonic and adult chick corneas reveals heretofore undetected changes in
      sulfation characteristics of KS and CS/DS disaccharides during corneal
      development.

PMID- 15851559
TI  - Dynamic changes in the tear film in dry eyes.
AB  - PURPOSE: To examine the dynamics of the tear film in patients with dry eye by
      measuring the wavefront aberrations of the anterior surface of the film. METHODS:
      Anterior surface aberrations for a 7-mm pupil were determined in 13 patients with
      dry eye at 1-second time intervals, for 15 seconds after a blink. The aberrations
      were calculated from the elevations provided by corneal topography. All data were
      decomposed using Zernike polynomials. Total, spherical, and comalike aberrations
      terms were studied separately. Results were compared with those in normal eyes.
      Outcome measures included comparison with clinical tear breakup time
      measurements. RESULTS: The total root mean square (RMS) wavefront aberration in
      patients with dry eye passed through in a minimum of 2.9 +/- 0.4 seconds after a
      blink in comparison to the minimum at 6.1 +/- 0.5 seconds in normal patients. In
      both groups, the minimum in total aberration appeared to be associated with
      similar changes in comalike aberrations, rather than in spherical aberrations,
      which increased monotonically with time. The time at which minimum RMS aberration
      occurred correlated reasonably well with the measured tear breakup times.
      CONCLUSIONS: Measurements of the dynamic changes in the optical aberrations
      introduced by the anterior tear film surface give valuable insights into tear
      film changes and may provide a convenient objective method for the diagnosis of
      dry eye.

PMID- 15851560
TI  - Sphere formation and expression of neural proteins by human corneal stromal cells
      in vitro.
AB  - PURPOSE: To demonstrate the presence of corneal stromal precursors that express
      neural markers in vitro. METHODS: To isolate sphere-forming cells, human corneal
      stromal cells were subjected to a reaggregation-free neurosphere assay in medium
      containing methylcellulose gel matrix. To promote differentiation, the isolated
      sphere colonies were plated in wells with medium containing fetal bovine serum.
      Expression of nestin, vimentin, keratocan, alpha-smooth muscle actin (alphaSMA),
      beta-III tubulin, neurofilament M (NFM), and glial fibrillary acidic protein
      (GFAP) was examined in the sphere colonies and their progeny (i.e., cells
      migrated from sphere colonies), by immunocytochemistry and/or reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Human corneal stromal
      cells formed sphere colonies that had no self-renewal capability. The frequency
      of sphere-forming cells was 1.5% +/- 0.1% (range, 1.3%-1.6%). Most of the cells
      within these colonies expressed nestin and vimentin, whereas some expressed beta
      III tubulin, NFM, GFAP, and alphaSMA by immunocytochemistry. Ninety-one percent
      and 89% of the progeny expressed vimentin and alphaSMA, respectively, whereas
      nestin was undetectable. beta-III tubulin-, NFM-, and GFAP-positive cells were
      detected in the progeny at the frequency of 7.2%, 0.9%, and 0.5%, respectively.
      Semiquantitative RT-PCR showed that nestin, NFM, GFAP, and keratocan gene
      expression was higher in the sphere colonies, whereas vimentin and alphaSMA
      expression increased in the progeny. CONCLUSIONS: Adult human corneal stroma
      contains precursor cells that express neural markers.

PMID- 15851561
TI  - Human corneal endothelial cell precursors isolated by sphere-forming assay.
AB  - PURPOSE: To isolate precursors of human corneal endothelial cells (HCECs) in
      vitro. METHODS: HCECs were subjected to a sphere-forming assay in which spheres
      floated in serum-free medium containing growth factors. To promote
      differentiation, the isolated sphere colonies were plated in dishes coated with
      poly-L-lysine (PLL)/laminin or fetal bovine endothelium extracellular matrix.
      Marker expression of neural and mesenchymal cells was examined in the sphere
      colonies and their progenies by immunocytochemistry and/or reverse transcription
      polymerase chain reaction (RT-PCR). Adherent differentiated cells from the sphere
      colonies were evaluated morphologically and functionally. RESULTS: HCECs formed
      primary and secondary spherical colonies, as shown by sphere-forming assay in
      vitro. The colonies expressed nestin, beta3-tublin, glial fibrillary acidic
      protein, and alpha-smooth muscle actin on immunocytochemistry. The progeny,
      proliferating on extracellular matrix derived from bovine corneal endothelium,
      but not on PLL/laminin-coated and noncoated dishes, expressed nestin and beta3
      tublin. These markers were confirmed by RT-PCR. Adherent differentiated cells
      from the sphere colonies had an HCEC-like hexagonal shape and satisfactory
      transport activity that is essential in HCECs. CONCLUSIONS: These findings
      indicate that the HCEC contains precursor cells with a propensity to
      differentiate into HCECs and that these cells can also produce neuronal and
      mesenchymal cell proteins.

PMID- 15851562
TI  - Ocular surface reconstruction using autologous rabbit oral mucosal epithelial
      sheets fabricated ex vivo on a temperature-responsive culture surface.
AB  - PURPOSE: Autologous stem cell transplantation for total limbal stem cell
      deficiency is immunologically preferable, to avoid allograft rejection. This
      study was undertaken to investigate the possibility of a novel tissue engineering
      approach for ocular surface reconstruction, using autologous oral mucosal
      epithelial stem cells expanded ex vivo on temperature-responsive cell culture
      surfaces. METHODS: Rabbit oral mucosal epithelial cells cultured on temperature
      responsive culture surfaces with mitomycin-C-treated 3T3 feeder cells for 2 weeks
      produced confluent epithelial cell sheets. Putative progenitor cell populations
      were estimated by colony-forming assays. Autologous transplantation of these cell
      sheets to surgically manipulated eyes was performed, and ocular surface
      reconstruction and cell phenotypic modulation were examined. RESULTS: All
      cultured oral epithelial cells were nonenzymatically harvested as transplantable
      intact cell sheets by reducing culture temperature to 20 degrees C. Oral
      epithelial cells were stratified in three to five cell layers more similar to
      corneal epithelium than to oral mucosal epithelium. Colony-forming assays and
      immunofluorescence for p63, beta1-integrin, and connexin 43 indicated retention
      of viable stem and/or progenitor cell populations in cell sheets. Autologous
      transplantation to rabbit corneal surfaces successfully reconstructed the corneal
      surface, with restoration of transparency. Four weeks after transplantation,
      epithelial stratification was similar to that in the corneal epithelium, although
      the keratin expression profile retained characteristics of the oral mucosal
      epithelium. CONCLUSIONS: Cell sheet harvest technology enables fabrication of
      viable, transplantable, tissue-engineered epithelial cell sheets that retain
      putative progenitor cells from autologous oral mucosal epithelial cells.
      Promising clinical capabilities for autologous tissue-engineered epithelial cell
      sheets for ocular surface reconstruction are indicated.

PMID- 15851563
TI  - Treatment of ocular tissues exposed to nitrogen mustard: beneficial effect of
      zinc desferrioxamine combined with steroids.
AB  - PURPOSE: Exposure of the ocular surface to mustard gas chemical warfare leads to
      a destructive inflammatory reaction. Both steroids and a novel metalocomplex free
      radical scavenger, zinc desferrioxamine (Zn/DFO), have been shown to be effective
      separately in reducing ocular damage. The purpose of the present study was to
      investigate whether the effectiveness of both medications applied simultaneously
      is superior to the effectiveness of either one applied alone. METHODS: One eye in
      each of 52 rabbits was exposed to 2% nitrogen mustard (NM). Topical treatment
      with eye drops of a metal complex-zinc desferrioxamine (Zn/DFO)-combined with
      dexamethasone phosphate (0.1%), was compared with the administration of saline or
      treatment with Zn/DFO or dexamethasone alone. Eight eyes (four animals) that were
      not exposed to NM served as the control. Examiners masked to the treatment groups
      assessed the extent of ocular injury and the response to treatment using
      clinical, histologic, and biochemical criteria. RESULTS: Treatment with the
      combination of Zn/DFO and dexamethasone was significantly more effective than was
      dexamethasone or Zn/DFO alone in reducing NM injury to ocular anterior segment
      structures. In combination-treated eyes, corneal re-epithelization was faster,
      corneal neovascularization was less severe, and intraocular pressure was not as
      severely elevated as in the saline or the Zn/DFO- or dexamethasone-alone groups.
      In addition, systemic antioxidant status was better conserved in the combination
      treated animals. CONCLUSIONS: The findings suggest that the combination of
      topically applied Zn/DFO and dexamethasone, by virtue of their additive
      inhibitory effects on free radical formation and inflammation, should be
      considered as a basis for the treatment of ocular mustard gas injuries.

PMID- 15851564
TI  - Flt-1 intraceptors inhibit hypoxia-induced VEGF expression in vitro and corneal
      neovascularization in vivo.
AB  - PURPOSE: To determine whether subunits of VEGF receptor-1 coupled with an
      endoplasmic reticulum retention signal can block hypoxia-induced upregulation of
      VEGF secretion in corneal epithelial cells and block murine corneal angiogenesis
      induced by corneal injury. METHODS: Human corneal epithelial cells, transfected
      with plasmids encoding Flt23K or Flt24K (the VEGF-binding domains of the Flt-1
      receptor coupled with the endoplasmic reticulum retention peptide KDEL), were
      subjected 2 days after transfection to 5% hypoxia for 24 hours. Supernatant was
      sampled at 24 hours and assayed for VEGF by ELISA. For in vivo models, mouse
      corneas underwent intrastromal injections of plasmids encoding Flt23K or Flt24K,
      and 2 days later, sustained injury induced by topical NaOH and mechanical
      scraping. Corneas were assessed 2 days later for VEGF ELISA and leukocyte
      counting or 1 week later for quantification of neovascularization. RESULTS:
      Hypoxia induced VEGF by human corneal epithelial cells was sequestered by both
      Flt23K and Flt24K; Flt-1 23K suppressed VEGF secretion as well. Intrastromal
      delivery of plasmid Flt23K suppressed VEGF by 40.4% (P = 0.009), leukocytes by
      49.4% (P < 0.001), and neovascularization by 66.8% (P = 0.001). Flt24K suppressed
      VEGF expression by 30.8% (P = 0.042), leukocytes by 25.8% (P < 0.001), and
      neovascularization by 49.5% (P = 0.015). CONCLUSIONS: Flt-1 intraceptors, which
      are endoplasmic reticulum retention signal-coupled VEGF receptors, significantly
      suppress hypoxia-induced VEGF secretion by corneal epithelial cells in vitro. In
      vivo, delivery of naked plasmids expressing these intraceptors inhibits injury
      induced upregulation of VEGF, leukocyte infiltration, and corneal
      neovascularization.

PMID- 15851565
TI  - Serum-free spheroid culture of mouse corneal keratocytes.
AB  - PURPOSE: To develop a serum-free mass culture system for mouse keratocytes.
      METHODS: Corneas of C57BL6/J mice were enzyme digested after the epithelium and
      endothelium were removed. Stromal cells were cultured in serum-free DMEM/F12
      (1:1) containing epidermal growth factor (EGF), fibroblast growth factor 2
      (FGF2), and B27 supplement. Primary spheres were dissociated by trypsin and
      subcultured as suspended secondary spheres. Cells from postnatal day (P)6 to P10
      spheres were subcultured onto plastic dishes or type I collagen gels for
      phenotype analysis. The expression of the keratocyte markers keratocan, aldehyde
      dehydrogenase (Aldh), and CD34, were analyzed by RT-PCR, and vimentin and alpha
      smooth muscle actin (alpha-SMA) were examined by immunocytochemistry. RESULTS:
      Primary keratocytes formed spheres, which were cultured for over 12 passages.
      Suspended sphere cells expressed vimentin, keratocan, CD34, and lumican, but were
      negative for cytokeratin K12 (K12) and Pax6. Sphere cells subcultured on plastic
      exhibited a dendritic morphology characteristic of keratocytes, and maintained
      keratocan, Aldh, and CD34 expression in serum-free medium. Sphere cells
      subcultured with 10% serum became fibroblastic, and expressed alpha-SMA when
      stimulated by transforming growth factor (TGF)-beta. alpha-SMA-positive cells
      demonstrated contractile properties on collagen gels, compatible with the
      myofibroblast phenotype. CONCLUSIONS: The phenotype of mouse keratocytes can be
      maintained in vitro for more than 12 passages by the serum-free sphere culturing
      technique.

PMID- 15851566
TI  - A new statistical approach for quantifying change in series of retinal and optic
      nerve head topography images.
AB  - PURPOSE: To describe and evaluate new statistical techniques for detecting
      topographic changes in series of retinal and optic nerve head images acquired by
      scanning laser tomography (Heidelberg Retinal Tomograph [HRT]; Heidelberg
      Engineering, Heidelberg, Germany). METHODS: Proven quantitative techniques,
      collectively referred to as statistic image mapping (SIM), are widely used in
      neuroimaging. These techniques are applied to HRT images. A pixel-by-pixel
      analysis of topographic height over time yields a statistic image that is
      generated by using permutation testing, derives significance limits for change
      wholly from the patient's own data, and removes the need for reference data sets.
      These novel techniques were compared to the Topographic Change Analysis (TCA
      super-pixel analysis) available in the current HRT software, by means of an
      extensive series of computer experiments. The SIM and TCA techniques were further
      tested and compared to linear regression of rim area (RA) against time, in real
      longitudinal HRT series of eyes of 20 normal subjects and 30 ocular hypertensive
      (OHT) patients that were known to have converted to glaucoma, on the basis of
      visual field criteria. RESULTS: Computer simulation indicated that SIM has better
      diagnostic precision at detecting change. In the real longitudinal series, SIM
      flagged false-positive structural progression in two (10%) of normal subjects,
      whereas TCA identified three (15%), and linear regression of RA against time
      identified two (10%). SIM identified 22 (73%) of the OHT converters as having
      structural progression, whereas the TCA and linear regression of RA against time
      each identified 16 (53%) over the course of the follow-up. CONCLUSIONS: SIM has
      better diagnostic precision in detecting change in series of HRT images when
      compared to current quantitative techniques. The clinical utility of these
      techniques will be established on further longitudinal data sets.

PMID- 15851567
TI  - Synthesis of alpha-chemokines IP-10, I-TAC, and MIG are differentially regulated
      in human corneal keratocytes.
AB  - PURPOSE: Chemokines responsible for recruiting lymphocytes such as activated T
      cells into the cornea have not been clearly defined. IP-10, I-TAC, and MIG are
      chemoattractants for these lymphocytes. The goal of this study was to determine
      whether human corneal keratocyte (HCKs) in culture synthesize these chemokines in
      response to proinflammatory mediators. METHODS: HCKs grown in vitro were
      stimulated with IL-1alpha, TNF-alpha, or IFN-gamma. Induction of alpha-chemokine
      gene expression was quantitated by real-time PCR and ELISA. Activation of the
      transcriptional activator STAT1 by IFN-gamma receptors expressed on HCKs was
      determined by Western blot analysis. RESULTS: HCKs incubated with TNF-alpha, IL
      1alpha, or IFN-gamma resulted in a >2000-fold increase in IP-10 protein secretion
      by 36 hours after stimulation. In contrast, stimulation with TNF-alpha, IL
      1alpha, or IFN-gamma induced levels of MIG and I-TAC that were not significantly
      greater than constitutive levels. Treatment of HCKs with IFN-gamma activated
      STAT1 and, in combination with either TNF-alpha or IL-1alpha, enhanced MIG and I
      TAC synthesis >20-fold. CONCLUSIONS: IP-10 synthesis is induced in HCKs by IL
      1alpha, TNF-alpha, and IFN-gamma. In contrast, induction of I-TAC and MIG
      synthesis in HCKs requires costimulation with IFN-gamma and either IL-1alpha or
      TNF-alpha. The results suggest therefore, that the upregulation of I-TAC and MIG
      gene expression at sites of corneal inflammation are more tightly regulated than
      that of IP-10. A role for differential induction of the three alpha-chemokine
      genes in corneal inflammatory processes at the eye surface is discussed.

PMID- 15851568
TI  - Local gene transfer to modulate rat corneal allograft rejection.
AB  - PURPOSE: Allograft rejection is the leading cause of corneal graft failure.
      CD4(+) T cells control the allograft response and represent targets for
      antirejection therapy. The purpose of this study was to transfer cDNA encoding a
      monomeric anti-CD4 antibody fragment to donor corneal endothelium, to attempt to
      modulate orthotopic corneal allograft rejection in the rat. METHODS: A
      replication-deficient adenoviral vector (AdV) encoding anti-CD4 single-chain,
      variable-domain antibody fragment (scFv) and enhanced green fluorescent protein
      (eGFP) was constructed (AdCD4GFP). AdV encoding eGFP alone (AdGFP) was used as a
      control. Transgenic product was detected by reverse transcription-polymerase
      chain reaction (RT-PCR), Western blot, flow cytometry, and fluorescence
      microscopy. The alloinhibitory capacity of anti-rat CD4 scFv was measured in the
      one-way mixed lymphocyte reaction (MLR). The survival of Wistar-Furth corneas
      transduced with AdV either immediately or 3 days before orthotopic
      transplantation in Fischer 344 recipients was examined. RESULTS: ScFv and eGFP
      mRNAs were detected in rat corneas transduced in vitro, and active scFv secreted
      in corneal supernatants peaked at days 4 to 5 after transduction at 23 +/- 4 ng
      of protein per cornea per day. Antibody and scFv against rat CD4 blocked
      alloproliferation in MLR. However, transduction of corneas with AdCD4GFP ex vivo,
      immediately before transplantation, or in vivo, 3 days before transplantation,
      did not significantly prolong corneal allograft survival (P > 0.05). CONCLUSIONS:
      Anti-CD4 scFvs were capable of blocking allostimulation, but their local
      expression within the eye did not prolong corneal allograft survival, suggesting
      that sensitization may still occur.

PMID- 15851569
TI  - Human lens phospholipid changes with age and cataract.
AB  - PURPOSE: To determine the phospholipid changes responsible for the increase in
      membrane lipid hydrocarbon chain order, or stiffness, with age and cataract in
      the human lens. METHODS: Clear human lenses were pooled into four groups, with
      donors ranging in age from 15 to 29, 30 to 49, 50 to 64, and 65 to 74 years.
      Whole human cataractous lenses were obtained from donors after extracapsular
      cataract extraction. Cataractous lenses were grouped into four classifications:
      mature, mixed cortical and nuclear, immature nuclear sclerotic, mature posterior
      subcapsular, and mature nuclear. Lipids were extracted and quantified
      gravimetrically. The relative phospholipid composition was determined by (31)P
      nuclear magnetic resonance spectroscopy. RESULTS: The relative and absolute
      amount of sphingolipids, including dihydrosphingomyelin and sphingomyelin,
      increased with age, whereas glycerolipids, including phosphatidylcholine and two
      phosphatidylethanolamine-related phospholipids, decreased. These changes were
      exacerbated by the presence of cataract and were substantial, greater than the
      changes in lipid levels reported in any organ in association with any disease.
      CONCLUSIONS: The changes in the amount of lipids with age and cataract support
      the idea that glycerolipids are selectively oxidized over lipids with fewer
      double bonds, such as sphingolipids. As a result of the elevation of sphingolipid
      levels with species, age, and cataract, lipid hydrocarbon chain order, or
      stiffness, increases. Increased membrane stiffness may increase light-scattering,
      reduce calcium pump activity, alter protein-lipid interactions, and perhaps slow
      fiber cell elongation.

PMID- 15851570
TI  - Noncontact optical measurement of lens capsule thickness in human, monkey, and
      rabbit postmortem eyes.
AB  - PURPOSE: To measure interspecies thickness differences in the central anterior
      and posterior capsules of postmortem crystalline lenses, by a technique that
      maintains the anatomic integrity of the lens. METHODS: Central capsule thickness
      was measured with a custom-built, noncontact optical system, using a focus
      detection technique. Anterior and posterior lens capsule thickness measurements
      were performed on 22 human, 29 monkey, and 34 New Zealand White rabbit intact
      postmortem lenses in situ. Eyes were prepared for optical measurements by bonding
      a PMMA ring to the sclera in the region of the ciliary body after the
      conjunctiva, adipose, and muscle tissues were removed. The posterior pole was
      removed by making a circumferential incision through the sclera approximately 7
      mm posterior to the limbus. Excess vitreous was removed to expose the posterior
      capsule surface, and the eye assembly was placed on a Teflon slide. The cornea
      and iris were sectioned to expose the anterior capsule surface. After the
      experiments, the lenses were excised, placed in 10% buffered formalin, and
      prepared for histology. Lens capsule thickness was measured from the histologic
      slides and compared to the optical RESULTS: results. Central anterior lens
      capsule thickness was 8.2 +/- 5.5 (human), 7.5 +/- 4.4 (monkey), and 10.7 +/- 4.2
      (rabbit) microm optically and 12.4 +/- 2.5 (human), 10.7 +/- 3.7 (monkey), and
      10.4 +/- 2.0 (rabbit) microm histologically. Central posterior capsule thickness
      was 6.3 +/- 2.2 (human), 5.9 +/- 1.7 (monkey), and 7.8 +/- 2.3 (rabbit) microm
      optically and 4.1 +/- 1.5 (human), 3.5 +/- 1.6 (monkey), and 4.7 +/- 2.5 (rabbit)
      microm histologically. CONCLUSIONS: The central anterior and posterior lens
      capsule thicknesses do not appear to vary considerably among human, rabbit, and
      monkey eyes. There were significant differences between optical in situ
      measurements and histology, which indicates that histologic preparation may
      affect lens capsule thickness.

PMID- 15851571
TI  - Ocular vasodynamic changes in light and darkness in smokers.
AB  - PURPOSE: To determine whether smokers have a reduced capacity for increased
      retinal blood flow velocity in darkness. METHODS: The peak systolic flow
      velocities (V(S)) and end diastolic flow velocities (V(D)) were measured by
      ultrasound (i.e., color Doppler equipment), in light and darkness in the
      ophthalmic and central retinal arteries in 20 cigarette smokers and 20 matched
      nonsmokers. The resistive index (RI) was calculated as RI = (V(S) - V(D))/V(S).
      RESULTS: In the ophthalmic artery in nonsmokers, the V(D) was markedly increased
      in darkness and the RI was correspondingly reduced. After the subject was re
      exposed to light, the RI was markedly increased. In smokers the V(S) and V(D) did
      not change significantly in the different conditions of light and darkness. In
      the central retinal artery in nonsmokers, the V(S) and V(D) were markedly
      increased in darkness and decreased after re-exposure to light. In smokers, the
      corresponding changes were much smaller and not significant. CONCLUSIONS: The
      normal capacity for increased blood flow velocity in the central retinal artery
      in darkness was markedly reduced in smokers. This finding may explain the reduced
      dark vision after recent smoking reported in several studies and probably
      reflects the combined effects of an increased blood viscosity, the
      vasoconstrictive action of nicotine, and a reduced capacity of the blood to
      transport oxygen, as the hemoglobin is partly occupied by carbon monoxide.

PMID- 15851572
TI  - Acute effects of PGF2alpha on MMP-2 secretion from human ciliary muscle cells: a
      PKC- and ERK-dependent process.
AB  - PURPOSE: Studies were designed to evaluate the cellular mechanisms associated
      with prostaglandin (PG)F(2alpha)-induced matrix metalloproteinase (MMP)-2
      secretion from human ciliary muscle (HCM) cells. METHODS: The secretion and
      activity of MMP-2 was determined by Western blot analysis and zymography, using
      conditioned medium and HCM cells. ERK1/2 activity was measured by in-gel kinase
      assay and Western blot analysis with anti-phospho-ERK1/2 antibodies. RESULTS:
      PGF(2alpha) increased the secretion of MMP-2 in a dose-dependent manner with an
      EC(50) of 2.7 x 10(-8) M. The addition of 1 muM PGF(2alpha) also increased MMP-2
      secretion in a time-dependent manner with maximum secretion occurring at 4 hours
      after administration. At 4 hours, the maximum increase in MMP-2 secretion and
      activity were 112% +/- 32% and 88% +/- 18%, respectively. The secretory action of
      PGF(2alpha) was inhibited by pretreatment with a protein kinase C (PKC)
      inhibitor, chelerythrine chloride; the FP receptor antagonist, AL-8810; and the
      MEK inhibitor, PD-98059. The addition of PGF(2alpha) and latanoprost acid
      increased ERK1/2 activity by 117% +/- 12% and 75% +/- 9%, respectively. The
      PGF(2alpha)- and latanoprost-acid-induced ERK1/2 activation was blocked by the
      presence of PKC inhibitors and downregulation of PKC by prolonged incubation with
      a phorbol ester. CONCLUSIONS: These data provide evidence that FP receptor
      activation leads to an increase in the secretion and activation of MMP-2 through
      PKC- and ERK1/2-dependent pathways. FP-agonist-induced activation of ERK1/2 was
      blocked by PKC inhibitors, indicating that PKC activation is required for ERK1/2
      activation and MMP-2 secretion from HCM cells. In the ciliary muscle, the
      functional responses to ERK1/2 activation include secretion of MMP-2, supporting
      the hypothesis that increases in uveoscleral outflow facility induced by PG
      administration involves the secretion and activation of MMP-2.

PMID- 15851573
TI  - Systemic hyperoxia and retinal vasomotor responses.
AB  - PURPOSE: Several studies have investigated the changes in retinal vessel diameter
      during physiological stress or pathologic conditions. These studies were
      principally based on individual fundus photographs and as such did not allow the
      evaluation of vessel dynamics over time. The research objective was to detail the
      time course and amplitude changes in the diameter of arteries and veins across
      all retinal quadrants, during and after hyperoxic vascular stress. METHODS: The
      dynamics of changes in retinal vessel diameter were quantified with a retinal
      vessel analyzer, which digitizes fundus images in real time and simultaneously
      quantifies vessel diameter. The arterial and venous diameters within one disc
      diameter of the optic nerve head in each quadrant were studied. Twenty young
      adults participated in this study in which the vessel diameters were measured
      during successive phases of breathing either room air or pure oxygen. The oxygen
      saturation level (SaO(2)), end-tidal carbon dioxide (EtCO(2)), pulse rate (PR),
      respiratory rate (RR), and blood pressure (BP) were also monitored throughout
      testing. RESULTS: Breathing 100% O(2) caused an increase in SaO(2) and a decrease
      in the EtCO(2). All other systemic parameters measured (PR, RR, BP, and ocular
      perfusion pressure [OPP]) remained unchanged. However, the retinal veins and
      arteries constricted by approximately 14% and approximately 9% respectively, in
      all retinal quadrants. After experimental hyperoxia, inhalation of room air was
      associated with a progressive increase in the caliber of vessels toward their
      pretest size. The amplitude and overall profile of vessel reactivity to and
      recovery from hyperoxia was the same across retinal quadrants. CONCLUSIONS: These
      data indicate that, during systemic hyperoxic stress, the retinal vessels change
      in caliber uniformly across retinal quadrants in healthy young adults. This type
      of physiological vascular provocation could be used to investigate the quality of
      vascular regulation during aging and in vascular diseases of the eye.

PMID- 15851574
TI  - Short-term increase of intraocular pressure does not alter the response of
      retinal and optic nerve head blood flow to flicker stimulation.
AB  - PURPOSE: It has been shown that stimulation with diffuse luminance flicker
      induces vasodilatation in the human retina and increases optic nerve head (ONH)
      blood flow. The present study was designed to investigate the influence of a
      short-term increase in intraocular pressure on flicker-induced changes in ONH
      blood flow and retinal vessel diameters. METHODS: In a group of 15 healthy
      volunteers, IOP was increased by the episcleral suction cup technique. ONH blood
      flow was assessed with a laser Doppler flowmeter, and retinal vessel diameters
      were measured with the retinal vessel analyzer. Flicker responses of retinal
      vessel diameters and ONH blood flow were determined at baseline conditions and
      during suction of 70 and 140 mm Hg. Flicker light consisted of 8-Hz square-wave
      flashes at a wavelength below 550 nm and produced a retinal irradiance of 140
      muW/cm(2). RESULTS: Suction increased IOP from 12 +/- 2 to 27 +/- 4 mm Hg and 43
      +/- 4 mm Hg. Stimulation with diffuse luminance flicker induced an increase in
      ONH blood flow of +24.0% +/- 20.7%. Increased IOP did not significantly change
      the flicker response in the ONH (+19.3% +/- 26.6% and +22.1% +/- 25.1%). In
      retinal veins, flicker induced an increase in vessel diameter of +3.0% +/- 2.0%.
      Flicker responses in retinal veins were not significantly altered after the IOP
      was increased, compared with those recorded at baseline IOP (+2.8% +/- 2.5% and
      +3.2% +/- 2.2%). The flicker response in retinal arteries at baseline IOP was
      +3.5% +/- 2.0%. Again, the increase in IOP did not significantly alter this
      flicker response (+2.8% +/- 1.6% and +3.1% +/- 2.4%). CONCLUSIONS: A short-term
      increase in IOP does not alter the response of retinal vessel diameters and ONH
      blood flow to diffuse luminance flicker, which indicates that increased IOP does
      not alter retinal or ONH regulation during neuronal stimulation.

PMID- 15851575
TI  - Association of HLA class I and class II polymorphisms with age-related macular
      degeneration.
AB  - PURPOSE: To evaluate whether HLA genotypes are associated with age-related
      macular degeneration (AMD). METHODS: HLA class I-A, -B, and -Cw and class II DRB1
      and DQB1 principal allele groups were genotyped in two stages: initially for
      principal allele groups in a cohort of 100 AMD cases and 92 control subjects, and
      then, in the next 100 cases and controls from the same cohort, for alleles or
      allele groups with P < 0.1 on initial typing. Genotype frequencies were compared
      by 2 x 2 contingency tables. The strongest associations for individual HLA
      alleles were calculated with two-locus stratification analysis and logistic
      regression for all possible pair-wise HLA combinations. Bonferroni corrections
      were applied for multiple measurements (P(c)). Each HLA allele was subjected to
      logistic regression for known AMD covariates. HLA immunohistochemistry for class
      I antigens was performed on elderly donor eyes. RESULTS: Allele Cw*0701 (P =
      0.004, P(c) = 0.036) correlated positively with AMD, whereas alleles B*4001 (P =
      0.003, P(c) = 0.027) and DRB1*1301(P = 0.001, P(c) = 0.009) were negatively
      associated. These HLA associations were independent of any linkage
      disequilibrium. Immunohistochemistry demonstrated differential HLA class I
      expression in choriocapillary endothelial cells. CONCLUSIONS: Significant
      positive and negative associations exist between HLA alleles and AMD. HLA
      polymorphisms influence the development of AMD, possibly via modulating choroidal
      immune function.

PMID- 15851576
TI  - Screen of the IMPDH1 gene among patients with dominant retinitis pigmentosa and
      clinical features associated with the most common mutation, Asp226Asn.
AB  - PURPOSE: To determine the frequency of mutations in IMPDH1 among patients with
      autosomal dominant retinitis pigmentosa (RP), to characterize the clinical
      features of patients with the Asp226Asn mutation in this gene, and to compare
      these features with those found among patients with selected dominant mutations
      in other RP genes. METHODS: The coding sequence and the adjacent flanking intron
      sequences of all 14 coding exons were sequenced in 183 unrelated patients with
      dominant RP. The clinical findings evaluated included visual acuity, refractive
      error, visual field area measured with the Goldmann perimeter, final dark
      adaptation threshold, full-field electroretinogram (ERG) amplitudes, cataract,
      and funduscopic bone spicule pigmentation. RESULTS: The mutation Asp226Asn was
      identified in 6 of the 183 unrelated patients with RP. One patient carried the
      novel, possibly pathogenic, change Lys238Glu. There was approximately a 100-fold
      variation in ERG amplitudes among patients of similar age with the Asp226Asn
      mutation. Patients had similar reductions of rod-plus-cone 0.5-Hz ERG amplitude
      and cone 30-Hz ERG amplitude. For a given amount of remaining visual field, there
      was a larger ERG amplitude in IMPDH1-carrying patients (average 0.5-Hz ERG/visual
      field ratio = 9.5 nV/deg(2)) compared with groups of patients with the RP1
      mutation Arg677End (2.8 nV/deg(2)), the rhodopsin (RHO) mutation Pro23His (5.1
      nV/deg(2)), or the RHO mutation Pro347Leu (1.7 nV/deg(2)). CONCLUSIONS: IMPDH1
      mutations account for approximately 2% of cases of dominant RP in North America.
      The most frequent mutation, Asp226Asn, appears to cause at least as much loss of
      rod function as cone function. Patients with this form of RP retain, on average,
      two to five times more ERG amplitude per unit of remaining visual area than
      patients with three other forms of dominant RP.

PMID- 15851577
TI  - Early-onset, autosomal recessive, progressive retinal atrophy in Persian cats.
AB  - PURPOSE: An early-onset retinal degenerative disease has been identified in
      Persian cats. This study genetically, clinically, and histologically
      characterized the disease. A breeding colony was established to assist with
      identification of the causative gene and to provide a resource for vision
      research. METHODS: Cats were produced from testcross breedings. Kittens underwent
      serial ophthalmic and neuro-ophthalmic examinations. Globes were harvested from
      age-matched affected, obligate carrier, and control cats and were evaluated by
      light microscopy. Fluorescein angiography assessed retinal and choroidal
      vasculature. RESULTS: Test breedings confirmed an autosomal recessive mode of
      inheritance. Rate and extent of disease progression were similar among individual
      affected cats. The earliest clinical signs (reduced pupillary light reflexes)
      were seen at 2 to 3 weeks of age. Retinal degeneration was virtually complete by
      16 weeks of age. Histologic changes progressed rapidly and paralleled clinical
      findings. Histologic lesions were limited to the photoreceptors, outer plexiform
      layer, and retinal pigment epithelium in all but the terminal stages, when subtle
      changes were noted within the inner nuclear layer. CONCLUSIONS: Characterized in
      this study was an autosomal recessive, early-onset, retinal degenerative disease
      in Persian cats that is likely to be more prevalent in this breed than previously
      suspected. This feline disease model may identify a new gene or provide
      biological insight into some forms of early-onset retinitis pigmentosa (RP) in
      humans and genetic retinal degenerations in other species. A breeding colony that
      will assist in the identification of the causative gene has been established and
      is available for studies in vision research.

PMID- 15851578
TI  - Time course of neurotrophic factor upregulation and retinal protection against
      light-induced damage after optic nerve section.
AB  - PURPOSE: To assess neurotrophic factor upregulation in the retina after damage to
      the optic nerve and relate that regulation to changes in photoreceptor stability
      and function. METHODS: Retinas of adult pigmented (Long-Evans) rats were examined
      at successive times (1-60 days) after unilateral optic nerve section. The
      distribution and expression of ciliary neurotrophic factor (CNTF) and basic
      fibroblast growth factor (FGF-2) and their receptor elements FGFR1 and CNTFRalpha
      were studied with immunohistochemistry and Western blot analysis. FGF-2 and CNTF
      mRNA levels were also assessed, with semiquantitative reverse transcription-PCR.
      Levels and localization of the intracellular signaling molecule ERK and its
      activated, phosphorylated form pERK, were examined by immunohistochemistry. To
      assess the correlation between neurotrophic factor levels and their protective
      effect against light damage, albino (Sprague-Dawley) rats were exposed to bright
      continuous light (1000 lux) for 24 or 48 hours at successive times after nerve
      section. The TUNEL technique was used to visualize neuronal cell death in the
      retina. RESULTS: CNTF upregulation was detected 1 week after optic nerve section,
      peaked at 2 weeks, and fell to control levels at 4 weeks. CNTF appeared first in
      the inner retina in the ganglion cells, then in the Muller cells in which it
      became prominent at the outer limiting membrane (OLM) and in the outer segment
      (OS) region of photoreceptors. FGF-2 upregulation became prominent, particularly
      in photoreceptors, 21 to 28 days after surgery, continued to 2 months, and slowly
      declined thereafter. Double labeling with antibodies to ligand and the receptor
      showed colocalization of CNTF to its receptor at the OS region, whereas FGF-2-to
      FGFR1 binding was found in the outer nuclear (ONL) and outer plexiform (OPL)
      layers. Optic nerve section provided a significant protective effect against
      light-induced damage in the first 2 weeks. There was no protection when animals
      were exposed to damaging light 1 month after nerve section. CONCLUSIONS: The
      upregulation of CNTF 7 to 14 days after nerve section correlates with a reduction
      in the a-wave described previously. Colocalization of CNTF and CNTFRalpha on the
      outer segments suggests that CNTF acts at the photoreceptor membrane. The slower
      upregulation of FGF-2 correlates with a reduction of the b-wave. FGF-2/FGFR1
      colocalization in the OPL suggests that this factor acts at the synaptic
      terminals of photoreceptors, modulating the release of neurotransmitters. The
      time course of pERK upregulation suggests that the successive upregulation of
      CNTF and FGF-2 activates the ERK pathway. Based on the time course of protection
      against bright continuous light, it seems that CNTF plays a major role in this
      effect, and FGF-2 has a less important role in the protection against light
      induced damage.

PMID- 15851580
TI  - Nuclear gene expression changes due to mitochondrial dysfunction in ARPE-19
      cells: implications for age-related macular degeneration.
AB  - PURPOSE: To measure changes in nuclear gene expression resulting from
      mitochondrial dysfunction in retinal pigment epithelial cells. METHODS: ARPE-19
      retinal pigment epithelial cells were depleted of their mitochondrial (mt)DNA by
      passaging in a low concentration of ethidium bromide. Loss of mitochondrial DNA
      was determined by uridine auxotrophy and quantitative real-time polymerase chain
      reaction of isolated DNA. Loss of mitochondrial membrane potential was estimated
      by uptake of JC-1. Changes in nuclear gene expression were determined by
      quantitative real-time reverse transcription-polymerase chain reaction of
      isolated total RNA from ethidium-bromide-treated and untreated cells. Morphologic
      and phenotypic changes were determined by phase-contrast microscopy, sensitivity
      to the oxidant tert-butyl hydroperoxide (tBH), and invasion assay. RESULTS: ARPE
      19 cells became auxotrophic for growth on uridine after eight passages in 50
      ng/mL ethidium bromide. Quantitative PCR revealed almost complete loss of
      mitochondrial DNA (rho(0) cells). Uptake of JC-1 was reduced in the rho(0) cells,
      indicating reduction of mitochondrial membrane potential. Quantitative RT-PCR
      measured increased expression of genes coding for drusen components, lipid
      transport, extracellular matrix components, and responses to inflammation in the
      rho(0) cells. The rho(0) cells also exhibited an increased sensitivity to killing
      by tBH and increased migration and invasion through solubulized basement membrane
      coated tissue culture inserts. CONCLUSIONS: ARPE-19 cells respond to loss of
      mitochondrial function by changes in nuclear gene expression that resemble
      changes observed in age-related macular degeneration. The results lead to the
      hypothesis that loss of mitochondrial function with age and resultant changes in
      nuclear gene expression may explain some of the changes in the macula that are
      associated with the known clinical manifestations of age-related macular
      degeneration.

PMID- 15851579
TI  - Human RPE expression of cell survival factors.
AB  - PURPOSE: To determine basal and tumor necrosis factor (TNF)-alpha-regulated
      expression of retinal pigment epithelial (RPE) cell survival factors and whether
      regulation is dependent on nuclear transcription factor (NF)-kappaB. METHODS:
      Cultured human RPE cells were infected with adenovirus encoding either mutant
      inhibitory (I)-kappaB or beta-galactosidase and treated with TNF-alpha for
      various times. Freshly prepared RPE/choroid and RPE samples were isolated from
      human donor eyes. Real-time reverse transcription-polymerase chain reaction,
      Western blot, and immunocytochemistry were used to determine survival factor gene
      expression, cellular protein levels, and localization, respectively. RESULTS:
      Multiple survival factor genes, including cellular inhibitor of apoptosis protein
      (c-IAP1), c-IAP2, TNF receptor-associated factor-1 (TRAF-1), TRAF-2, B-cell
      leukemia/lymphoma-2 (Bcl-2), Bcl-x, A1, and cellular Fas-associated death domain
      (FADD)-like interleukin-1beta-converting enzyme-like inhibitory protein (c-FLIP),
      were expressed in basal conditions in both cultured RPE cells and RPE cells in
      situ, whereas survivin was expressed only by cultured cells. TNF-alpha
      upregulated expression of TRAF-1, TRAF-2, c-IAP1, c-IAP2, c-FLIP, and A1. TRAF-1,
      c-FLIP, and to a lesser extent c-IAP2 protein levels were increased by TNF-alpha
      in a time-dependent manner, whereas c-IAP1, survivin, Bcl-x(L), and TRAF-2
      protein levels were not influenced by TNF-alpha treatment at any time point
      tested. In contrast, Bcl-2 and A1 proteins were not detected under basal
      conditions or after TNF-alpha treatment. Overexpression of mutant IkappaB blocked
      TNF-alpha-induced TRAF-1, TRAF-2, c-IAP1, c-IAP2, c-FLIP, and A1 gene expression
      and downregulated TRAF-1 protein levels. TRAF-1 and Bcl-x(L) proteins were
      localized diffusely in RPE cytoplasm. CONCLUSIONS: Multiple RPE cell survival
      factors are expressed by human RPE cells. TNF-alpha regulates expression of some
      of these factors in an NF-kappaB-dependent manner, whereas others are not
      influenced by NF-kappaB. RPE cell survival factors may protect RPE cells from
      apoptosis normally and in diseases such as age-related macular degeneration (AMD)
      and proliferative vitreoretinopathy (PVR).

PMID- 15851581
TI  - Useful visual field reduction as a function of age and risk of accident in
      simulated car driving.
AB  - PURPOSE: To study the relationships between the reduction of the useful visual
      field, age, and driving performance. METHODS: Forty-eight subjects, aged from 23
      to 77 years performed a test to evaluate the size of their useful visual fields.
      The test involved the detection and localization of peripheral signals that could
      appear in an area of 70 degrees of visual angle. The subjects then performed a
      simulated car-driving task involving the management of a situation that could
      lead to an accident. RESULTS: The analysis of the data revealed that the ability
      to process peripheral signals and simulated driving performance (vehicle speed)
      deteriorate with age. Simulated driving performance and useful visual field
      measurement have been analyzed jointly. The results indicate that the reduction
      of the useful visual field, estimated using a target-localization task, is
      related to the individual's ability to manage the simulated driving situation
      (correlation coefficient with speed = -0.43 and with reaction time for avoidance
      of a mobile obstacle = +0.30) and the deterioration of the useful visual field
      estimated using a target detection task is related only to vehicle speed
      (correlation coefficient = -0.32). CONCLUSIONS: The adoption of a lower speed by
      the drivers with a reduced visual field (the elderly ones) is probably an
      adaptation strategy to process the peripheral information. All useful visual
      field measurements do not seem to be equivalent to estimate the ability to
      process information relative to the mobile obstacle. The risk of collision should
      be estimated only with a useful visual field test using a target localization
      task.

PMID- 15851582
TI  - Cortical activation via an implanted wireless retinal prosthesis.
AB  - PURPOSE: To demonstrate local cortical activations in the primary visual cortex
      of the cat as a result of retinal electrical stimulation by means of a completely
      wireless-controlled, implantable retinal prosthesis in a series of acute
      experiments. METHODS: The transfer of energy to drive the device and signals to
      activate any combination of 25 retinal electrodes was achieved completely
      wirelessly by an external transmitter positioned in front of the eye.
      Individually configured electrical stimuli were applied via any combination of 25
      electrodes, on sending the necessary pulse parameters to the implant. Placement
      of the implant onto the retinal surface was achieved after lensectomy and
      vitrectomy in the cat. Fixation was performed with a retinal tack. Cortical
      activation patterns were recorded by means of optical imaging of intrinsic
      signals. RESULTS: Implantation and fixation were successfully performed in three
      cats. Wireless activation of the implant by radiofrequency was demonstrated by
      recording of stimulus artifacts from the sclera. Local activation of the visual
      cortex measured by optical imaging of intrinsic signals revealed a shift of
      cortical response that was well correlated with a change in the position of the
      activated retinal electrodes. CONCLUSIONS: The results demonstrate the
      retinotopic activation of the visual cortex using a completely wireless, remote
      controlled retinal implant.

PMID- 15851583
TI  - A VEP measure of the binocular fusion of horizontal and vertical disparities.
AB  - PURPOSE: Because of the lateral separation of the orbits, the retinal images
      differ in the two eyes. These differences are reconciled into a single image
      through sensory and motor fusional mechanisms. This study demonstrates
      electrophysiologically the effects that normal horizontal and vertical fusional
      processes have on the processing of monocular position signals. METHODS: VEPs
      were recorded in 16 healthy adults in response to a vernier onset-offset target
      presented to one eye. The vernier offsets appeared and disappeared at 2 Hz and
      were introduced into bar targets that were oriented either vertically (horizontal
      offsets) or horizontally (vertical offsets). The magnitude of the offsets was
      varied over the range of 0.5 to 10 arc min. VEP amplitude was measured as a
      function of the size of the dynamic offset under monocular viewing conditions and
      in the presence of two different static targets presented to the other eye. One
      of the static targets matched the dynamic test, except that it had no vernier
      offsets. The other static target, the static pedestal, matched the dynamic test,
      but contained a set of static vernier offsets in locations corresponding to the
      locations of the dynamic offsets presented to the other eye. RESULTS: VEP
      amplitude was a monotonically increasing function of vernier offset size under
      monocular viewing conditions. The addition of the static target without offsets
      in the other eye resulted in an increased amplitude VEP response. The addition of
      the static target with vernier offsets resulted in a decrease in VEP amplitude
      for both horizontal and vertical disparities. CONCLUSIONS: The normal process of
      fusion results in a single visual direction. To obtain a single visual direction,
      the visual system must synthesize a binocular visual direction that differs from
      the monocular components. One of the conditions (the static pedestal with
      offsets) produces binocular visual direction shifts that degrade the appearance
      of vernier onset-offset, and reduce VEP amplitude for both horizontal and
      vertical disparities. This characteristic evoked response marker is a promising
      tool for measuring binocular fusion objectively in patients with strabismus.

PMID- 15851584
TI  - Cognition, ocular accommodation, and cardiovascular function in emmetropes and
      late-onset myopes.
AB  - PURPOSE: To investigate objectively and noninvasively the role of cognitive
      demand on autonomic control of systemic cardiovascular and ocular accommodative
      responses in emmetropes and myopes of late-onset. METHODS: Sixteen subjects (10
      men, 6 women) aged between 18 and 34 years (mean +/- SD: 22.6 +/- 4.4 years),
      eight emmetropes (EMMs; mean spherical equivalent [MSE] refractive error +/- SD:
      0.05 +/- 0.24 D) and eight with late-onset myopia (LOMs; MSE +/- SD: -3.66 +/-
      2.31 D) participated in the study. Subjects viewed stationary numerical digits
      monocularly within a Badal optical system (at both 0.0 and -3.0 D) while
      performing a two-alternative, forced-choice paradigm that matched cognitive
      loading across subjects. Five individually matched cognitive levels of increasing
      difficulty were used in random order for each subject. Five 20-second, continuous
      objective recordings of the accommodative response measured with an open-view
      infrared autorefractor were obtained for each cognitive level, whereas
      simultaneous measurement of heart rate was continuously recorded with a finger
      mounted piezoelectric pulse transducer for 5 minutes. Fast Fourier transformation
      of cardiovascular function allowed the relative power of the autonomic components
      to be assessed in the frequency domain, whereas heart period gave an indication
      of the time-domain response. RESULTS: Increasing the cognitive demand led to a
      significant reduction in the accommodative response in all subjects (0.0 D: by 
      0.35 +/- 0.33 D; -3.0 D: by -0.31 +/- 0.40 D, P < 0.001). The greater lag of LOMs
      compared with EMMs was not significant (P = 0.07) at both distance (0.38 +/- 0.35
      D) and near (0.14 +/- 0.42 D). Mean heart period reduced with increasing levels
      of workload (P < 0.0005). LOMs exhibited a relative elevation in sympathetic
      system activity compared to EMMs. Within refractive groups, however,
      accommodative shifts with increasing cognition correlated with parasympathetic
      activity (r = 0.99, P < 0.001), more than with sympathetic activity (r = 0.62, P
      > 0.05). CONCLUSIONS: In an equivalent workload paradigm, increasing cognitive
      demand caused a reduction in accommodative response that was attributable
      principally to a concurrent reduction in the relative power of the
      parasympathetic component of the autonomic nervous system (ANS). The disparity in
      accommodative response between EMMs and LOMs, however, appears to be augmented by
      changes in the sympathetic nervous component of the systemic ANS.

PMID- 15851585
TI  - Inducing form-deprivation myopia in fish.
AB  - PURPOSE: To induce form deprivation myopia in fish and investigate the role of
      the lens in the development of refractive error. METHODS: Tilapia (Oreochromis
      niloticus), approximately 4 months old and from 26 to 63 g, were divided into
      three groups. Translucent goggles were directly sutured over the right eye for 4
      weeks to induce form-deprivation myopia; the left eye served as an untreated
      contralateral control. The refractive state was measured by retinoscopy. Ocular
      dimensions were determined from frozen sections and with ultrasound
      biomicroscopy, and a scanning laser system was used to determine the optical
      quality of excised lenses. RESULTS: After 4 weeks of form-deprivation treatment,
      all the deprived fish eyes showed development of significant amounts of myopia
      ranging from -3.75 to -26.25 D, with the average amounting to -10.27 +/- 1.14 D.
      Eye dimension measurements show that the vitreous and anterior chambers of the
      treated eye are significantly longer axially than those of the contralateral
      eyes. No significant change in optical quality was found between lenses of the
      myopic and nonmyopic eyes. The fish recovered completely from the myopia 5 days
      after the goggle was removed. CONCLUSIONS: Although lower vertebrates are capable
      of lifelong growth, their eyes are susceptible to form-deprivation myopia. Thus,
      the visual environment is an important factor controlling ocular development in
      lower vertebrates, as well as in higher ones, and eye development is not strictly
      genetically determined. This study also indicates that lens growth and optical
      development are largely independent from the refractive development of the whole
      eye.

PMID- 15851586
TI  - Prognostic implications of warfarin cessation after major trauma: a population
      based cohort analysis.
AB  - BACKGROUND: Warfarin therapy is often withheld from elderly patients who fall or
      otherwise experience injury because of concerns regarding the long-term risk of
      hemorrhage in these individuals. We studied whether stopping warfarin after
      trauma is associated with a higher risk of subsequent adverse cardiovascular
      events. METHODS AND RESULTS: We conducted a retrospective, population-based,
      cohort study using linked administrative databases in the province of Ontario,
      Canada for the years 1992 to 2001. A total of 8450 elderly patients (age >65
      years) who survived an incident of major trauma and were receiving warfarin
      before injury were followed up for a mean of 3.3 years. During the 6-month
      interval after trauma, 1827 (22%) patients discontinued warfarin, whereas 6623
      (78%) patients continued warfarin. Warfarin cessation was not associated with an
      increased risk of subsequent stroke (hazard ratio [HR] 0.99, 95% CI 0.82 to 1.21)
      or myocardial infarction (HR 0.94, 95% CI 0.74 to 1.20) but was associated with a
      lower risk of major hemorrhage (HR 0.69, 95% CI 0.54 to 0.88) and a higher risk
      of venous thromboembolism (HR 1.59, 95% CI 1.07 to 2.36). Adjustment for baseline
      demographics, stroke risk factors, other comorbidities, and characteristics of
      the trauma did not materially change these findings. On-treatment analyses
      yielded similar results. CONCLUSIONS: Cessation of warfarin in elderly patients
      after major trauma was not associated with an increased risk of arterial
      thrombotic events but was associated with a significantly increased risk of
      venous thromboembolism.

PMID- 15851587
TI  - Tissue-type plasminogen activator crosses the intact blood-brain barrier by low
      density lipoprotein receptor-related protein-mediated transcytosis.
AB  - BACKGROUND: Accumulating evidence demonstrates a critical involvement of tissue
      type plasminogen activator (tPA) in pathological and physiological brain
      conditions. Determining whether and how vascular tPA can cross the blood-brain
      barrier (BBB) to enter the brain is thus important, not only during stroke but
      also in physiological conditions. METHODS AND RESULTS: In the present work, we
      provide evidence in vivo that intravenous injection of tPA increases NMDA-induced
      striatal lesion in the absence of BBB leakage. Accordingly, we show that tPA
      crosses the BBB both after excitotoxic lesion and in control conditions. Indeed,
      vascular injected tPA can be detected within the brain parenchyma and in the
      cerebrospinal fluid. By using an in vitro model of BBB, we have confirmed that
      tPA can cross the intact BBB. Its passage was blocked at 4 degrees C, was
      saturable, and was independent of its proteolytic activity. We have shown that
      tPA crosses the BBB by transcytosis, mediated by a member of the LDL receptor
      related protein family. CONCLUSIONS: We demonstrate that blood-derived tPA can
      reach the brain parenchyma without alteration of the BBB. The molecular mechanism
      of the passage of tPA from blood to brain described here could represent an
      interesting target to improve thrombolysis in stroke.

PMID- 15851588
TI  - Left ventricular systolic performance, function, and contractility in patients
      with diastolic heart failure.
AB  - BACKGROUND: Patients with diastolic heart failure (DHF) have significant
      abnormalities in left ventricular (LV) diastolic function, including slow and
      delayed relaxation and increased chamber stiffness. Whether and to what extent
      these abnormalities in diastolic function occur in association with abnormalities
      in LV systolic performance, function, and contractility has not been investigated
      thoroughly. METHODS AND RESULTS: The systolic properties of the LV were examined
      in 75 patients with heart failure and a normal ejection fraction (ie, DHF) and 75
      normal control subjects with no evidence of cardiovascular disease. LV systolic
      properties were assessed with echocardiographic and cardiac catheterization data.
      Stroke work (an index of LV systolic performance), preload recruitable stroke
      work and ejection fraction (indices of LV systolic function), systolic stress
      shortening relationship, end-systolic pressure-volume relationship, and peak
      (+)dP/dt (indices of LV contractility) were examined. The systolic properties of
      the LV were normal in patients with DHF. Stroke work was 8.4+/-2.3 in DHF versus
      8.8+/-2.5 kg . cm in controls (P=0.26). Preload recruitable stroke work was 99+/
      22 in DHF versus 109+/-18 g/cm2 in controls (P=0.13). The relationship between
      stroke work and end-diastolic volume was similar in DHF and controls. Peak (+)
      dP/dt was 1596+/-362 in DHF versus 1664+/-305 mm Hg/s in controls (P=0.54). The
      end-systolic pressure-volume relationship was increased in DHF. The systolic
      stress versus endocardial fractional shortening relationship was similar in DHF
      and controls. CONCLUSIONS: Patients with DHF had normal LV systolic performance,
      function, and contractility. The pathophysiology of DHF does not appear to be
      related to significant abnormalities in these systolic properties of the LV.

PMID- 15851589
TI  - Reduced ABCA1-mediated cholesterol efflux and accelerated atherosclerosis in
      apolipoprotein E-deficient mice lacking macrophage-derived ACAT1.
AB  - BACKGROUND: Macrophage acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1) and
      apolipoprotein E (apoE) have been implicated in regulating cellular cholesterol
      homeostasis and therefore play critical roles in foam cell formation. Deletion of
      either ACAT1 or apoE results in increased atherosclerosis in hyperlipidemic mice,
      possibly as a consequence of altered cholesterol processing. We have studied the
      effect of macrophage ACAT1 deletion on atherogenesis in apoE-deficient (apoE-/-)
      mice with or without the restoration of macrophage apoE. METHODS AND RESULTS: We
      used bone marrow transplantation to generate apoE-/- mice with macrophages of 4
      genotypes: apoE+/+/ACAT1+/+ (wild type), apoE+/+/ACAT1-/- (ACAT-/-), apoE-/
      /ACAT1+/+ (apoE-/-), and apoE-/-/ACAT1-/- (2KO). When macrophage apoE was
      present, plasma cholesterol levels normalized, and ACAT1 deficiency did not have
      significant effects on atherogenesis. However, when macrophage apoE was absent,
      ACAT1 deficiency increased atherosclerosis and apoptosis in the proximal aorta.
      Cholesterol efflux to apoA-I was significantly reduced (30% to 40%; P<0.001) in
      ACAT1-/- peritoneal macrophages compared with ACAT1+/+ controls regardless of
      apoE expression. 2KO macrophages had a 3- to 4-fold increase in ABCA1 message
      levels but decreased ABCA1 protein levels relative to ACAT1+/+ macrophages.
      Microarray analyses of ACAT1-/- macrophages showed increases in proinflammatory
      and procollagen genes and decreases in genes regulating membrane integrity,
      protein biosynthesis, and apoptosis. CONCLUSIONS: Deficiency of macrophage ACAT1
      accelerates atherosclerosis in hypercholesterolemic apoE-/- mice but has no
      effect when the hypercholesterolemia is corrected by macrophage apoE expression.
      However, ACAT1 deletion impairs ABCA1-mediated cholesterol efflux in macrophages
      regardless of apoE expression. Changes in membrane stability, susceptibility to
      apoptosis, and inflammatory response may also be important in this process.

PMID- 15851590
TI  - Coronary circulatory dysfunction in insulin resistance, impaired glucose
      tolerance, and type 2 diabetes mellitus.
AB  - BACKGROUND: Abnormal coronary endothelial reactivity has been demonstrated in
      diabetes and is associated with an increased rate of cardiovascular events. Our
      objectives were to investigate the presence of functional coronary circulatory
      abnormalities over the full spectrum of insulin resistance and to determine
      whether these would differ in severity with more advanced states of insulin
      resistance. METHODS AND RESULTS: Myocardial blood flow (MBF) was measured with
      positron emission tomography and 13N-ammonia to characterize coronary circulatory
      function in states of insulin resistance without carbohydrate intolerance (IR),
      impaired glucose tolerance (IGT), and normotensive and hypertensive type 2
      diabetes mellitus (DM) compared with insulin-sensitive (IS) individuals. Indices
      of coronary function were total vasodilator capacity (mostly vascular smooth
      muscle-mediated) during pharmacological vasodilation and the nitric oxide
      mediated, endothelium-dependent vasomotion in response to cold pressor testing.
      Total vasodilator capacity was similar in normoglycemic individuals (IS, IR, and
      IGT), whereas it was significantly decreased in normotensive (-17%) and
      hypertensive (-34%) DM patients. Compared with IS, endothelium-dependent coronary
      vasomotion was significantly diminished in IR (-56%), as well as in IGT and
      normotensive and hypertensive diabetic patients (-85%, -91%, and -120%,
      respectively). CONCLUSIONS: Progressively worsening functional coronary
      circulatory abnormalities of nitric oxide-mediated, endothelium-dependent
      vasomotion occur with increasing severity of insulin-resistance and carbohydrate
      intolerance. Attenuated total vasodilator capacity accompanies the more
      clinically evident metabolic abnormalities in diabetes.

PMID- 15851591
TI  - Infarct-sparing effect of A2A-adenosine receptor activation is due primarily to
      its action on lymphocytes.
AB  - BACKGROUND: A2A-adenosine receptor (A2AAR) activation on reperfusion after
      ischemia reduces the size of myocardial infarction, but the mechanism of action
      has not been fully defined. METHODS AND RESULTS: We created chimeric mice by bone
      marrow transplantation from A2AAR-knockout or green fluorescent donor mice to
      irradiated congenic C57BL/6 (B6) recipients. In the GFP chimeras, we were unable
      to detect green fluorescent-producing cells in the vascular endothelium,
      indicating that bone marrow-derived cells were not recruited to endothelium at
      appreciable levels after bone marrow transplantation and/or acute myocardial
      infarction. Injection of 5 or 10 microg/kg of a potent and selective agonist of
      A2AAR, ATL146e, had no effect on hemodynamic parameters but reduced infarct size
      in B6 mice after 45 minutes of left anterior descending artery occlusion followed
      by 24 hours of reperfusion to 42.5+/-3.0% and 39.3+/-4.7% of risk region,
      respectively, compared with 61.0+/-2.3% in vehicle-treated B6 mice (P<0.05).
      Myocardial myeloperoxidase activity in the risk region measured at 4 hours after
      reperfusion was significantly reduced by ATL146e. The salutary effects of ATL146e
      were absent in A2AAR-knockout mice or in mice treated with a selective A2AAR
      antagonist, ZM241385. ATL146e also reduced infarct size and myeloperoxidase in
      B6/B6 (donor/recipient) chimeras (P<0.05) but not in A2AAR-knockout/B6 chimeras.
      In immunocompromised Rag-1-KO mice, infarct size was significantly reduced
      compared with B6 mice but was not further reduced by ATL146e. CONCLUSIONS: The
      results indicate that A2AAR activation on bone marrow-derived cells, specifically
      T or B lymphocytes, is responsible for the infarct-sparing and antiinflammatory
      effects of ATL146e administered at the time of reperfusion after coronary
      occlusion.

PMID- 15851592
TI  - Endothelium-intrinsic requirement for Hif-2alpha during vascular development.
AB  - BACKGROUND: The development of the vascular system is a complex process that
      involves communications among multiple cell types. As such, it is important to
      understand whether a specific gene regulates vascular development directly from
      within the vascular system or indirectly from nonvascular cells. Hypoxia
      inducible factor-2alpha (Hif-2alpha, or endothelial PAS protein-1 [EPAS-1]) is
      required for vascular development in mice, but it is not clear whether its
      requirement resides directly in endothelial cells. METHODS AND RESULTS: To
      address this issue, we expressed Hif-2alpha cDNA in the vascular endothelium of
      Hif-2alpha-/- embryos by an embryonic stem (ES) cell-mediated transgenic approach
      and assessed whether endothelium-specific reexpression of Hif-2alpha could rescue
      vascular development. Here we report that although ES cell-derived Hif-2alpha-/-
      embryos developed severe vascular defects by embryonic day (E) 11.5 and died in
      utero before E12.5, endothelium-specific expression of Hif-2alpha cDNA restored
      normal vascular development at all stages examined (up to E14.5) and allowed Hif
      2alpha-/- embryos to survive at a frequency comparable to that of Hif-2alpha+/-
      embryos. Furthermore, we found that Tie-2 expression was significantly reduced in
      Hif-2alpha-/- mutants but was restored by Hif-2alpha cDNA expression.
      CONCLUSIONS: These data demonstrate an intrinsic requirement for Hif-2alpha by
      endothelial cells and imply that hypoxia may control endothelial functions
      directly via Hif-2alpha-regulated Tie-2 expression.

PMID- 15851593
TI  - Inflammation and Carotid Artery--Risk for Atherosclerosis Study (ICARAS).
AB  - BACKGROUND: Compelling evidence suggests that inflammation is fundamentally
      involved in the pathogenesis of atherosclerosis; however, temporal correlation
      between inflammation and morphological features of atherosclerosis progression
      has not been demonstrated unequivocally. METHODS AND RESULTS: We prospectively
      studied 1268 consecutive patients who were initially asymptomatic with respect to
      carotid artery disease. Patients underwent serial carotid ultrasound
      investigations at baseline and after a follow-up interval of a median of 7.5
      months (range 6 to 9 months), with measurement of carotid flow velocities and
      categorization of carotid arteries as 0% to 29%, 30% to 49%, 50% to 69%, 70% to
      89%, or 90% to 99% stenosed or occluded. High-sensitivity C-reactive protein (hs
      CRP) and serum amyloid A (SAA) were measured at baseline and follow-up.
      Progression of carotid atherosclerosis was found in 103 (8.1%) of 1268 patients.
      Hs-CRP and SAA, respectively, at baseline (P=0.004 and P=0.014) and follow-up
      (P<0.001 and P<0.001) and the change from baseline to follow-up (P<0.001 and
      P<0.001) were significantly associated with progressive atherosclerosis. Adjusted
      ORs (95% CI) for atherosclerosis progression with increasing quintiles of
      baseline hs-CRP were 1.65 (0.71 to 3.84), 1.87 (0.8 to 4.37), 3.32 (1.49 to
      7.39), and 3.65 (1.65 to 8.08), and with increasing quintiles of baseline SAA,
      they were 0.86 (0.38 to 1.92), 0.99 (0.49 to 1.99), 1.72 (0.91 to 3.28), and 2.28
      (1.24 to 4.20), respectively, compared with the lowest quintiles. CONCLUSIONS:
      These findings supply evidence for a close temporal correlation between
      inflammation and morphological features of rapidly progressive carotid
      atherosclerosis, which suggests that elevation or increase of the inflammatory
      biomarkers hs-CRP and SAA identifies the presence of active atherosclerotic
      disease.

PMID- 15851594
TI  - Functional ephrin-B2 expression for promotive interaction between arterial and
      venous vessels in postnatal neovascularization.
AB  - BACKGROUND: Ephrin-B2, one of the transmembrane ligands, is a genetic marker of
      arterial endothelial cells (ECs) at embryonic stages and is essential for
      cardiovascular development, but its roles in ischemic cardiovascular disease are
      not well understood. In this study, we focused on the function of ephrin-B2 in
      postnatal neovascularization. METHODS AND RESULTS: We found that ephrin-B2 is
      exclusively expressed and significantly upregulated in the arterial vasculature
      after the initial angiogenic responses in tissue ischemia. Upregulation of ephrin
      B2 is also observed in EC cordlike formation in vitro. Interestingly, ephrin-B2
      expression on ECs was enhanced by promotive angiogenic growth factors, such as
      vascular endothelial growth factor, basic fibroblast growth factor, and
      hepatocyte growth factor, whereas it was attenuated by angiopoietin-1, a factor
      for blood vessel maturation. Moreover, an ephrin-B2-rich environment was shown to
      induce neovascularization mainly through venous angiogenesis in an in vivo cornea
      micropocket assay. CONCLUSIONS: Our study indicates that the ephrin-B2 ligand is
      likely to have functional expression on angiogenic arterial ECs and induce a
      subsequent promotive effect on venous vessels during postnatal
      neovascularization.

PMID- 15851595
TI  - Hospital volume and selection of valve type in older patients undergoing aortic
      valve replacement surgery in the United States.
AB  - BACKGROUND: Hospital volume has been linked to quality of care. The relation
      between hospital volume and recommended use of bioprosthetic valves in older
      patients undergoing aortic valve replacement (AVR) is unknown. METHODS AND
      RESULTS: We identified 80,470 patients aged > or =65 years undergoing isolated
      AVR (with or without bypass surgery) in 1045 US hospitals during 1999-2001 from
      Medicare Part A files. International Classification of Diseases, Ninth Revision,
      Clinical Modification codes were used to identify patients undergoing
      bioprosthetic valve (35.21) or mechanical valve (35.22) AVR. The sample was
      categorized into deciles on the basis of the valve surgery volume of the
      hospital. Generalized estimating equations determined the relative risk of
      receiving a bioprosthetic valve in different volume deciles, with adjustment for
      age, gender, race, comorbidity, and other factors. Bioprosthetic valve use
      increased (P<0.001) from 44% in 1999 to 52% in 2001 and with age (from 36% in
      patients aged 65 to 69 years to 60% in patients aged > or =90 years). Rates were
      directly related (P<0.001) to volume, rising from 28% in the 1st decile to 68% in
      the 10th decile. With the use of generalized estimating equations, the relative
      risk of bioprosthetic valve use, relative to the 1st decile, progressively
      increased from 1.2 (95% CI, 1.1 to 1.4) in the 2nd decile to 2.3 (95% CI, 1.9 to
      2.7) in the 10th decile. CONCLUSIONS: Hospital volume was a strong predictor of
      bioprosthetic valve use in older patients undergoing AVR. The lower use of
      bioprosthetic valves in low-volume hospitals is at odds with recent guidelines
      recommending bioprosthetic valves in patients aged > or =65 years. These findings
      further support the use of volume as a marker of hospital quality.

PMID- 15851596
TI  - Fasudil, a Rho-kinase inhibitor, attenuates angiotensin II-induced abdominal
      aortic aneurysm in apolipoprotein E-deficient mice by inhibiting apoptosis and
      proteolysis.
AB  - BACKGROUND: Angiotensin II (Ang II) accelerates atherosclerosis and induces
      abdominal aortic aneurysm (AAA) in an experimental mouse model. Agonism of a G
      protein-coupled receptor by Ang II activates Rho-kinase and other signaling
      pathways and results in activation of proteolysis and apoptosis. Enhanced
      proteolysis and smooth muscle cell apoptosis are important mechanisms associated
      with AAA. In this study, we tested the hypothesis that fasudil, a Rho-kinase
      inhibitor, could attenuate Ang II-induced AAA formation by inhibiting vascular
      wall apoptosis and extracellular matrix proteolysis. METHODS AND RESULTS: Six
      month-old apolipoprotein E-deficient mice were infused with Ang II (1.44 mg x kg(
      1) x d(-1)) for 1 month. Animals were randomly assigned to treatment with fasudil
      (136 or 213 mg x kg(-1) x d(-1) in drinking water) or tap water. Ang II infusion
      induced AAA formation in 75% of the mice, which was accompanied by an increase in
      proteolysis detected by zymographic analysis and quantified by active matrix
      metalloproteinase-2 activity, as well as apoptosis detected by terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling and quantified by
      both caspase-3 activity and histone-associated DNA fragmentation. The level of
      DNA fragmentation in the suprarenal aorta correlated with AAA diameter. Ang II
      also increased atherosclerotic lesion area and blood pressure. Fasudil treatment
      resulted in a dose-dependent reduction in both the incidence and severity of AAA.
      At the higher dose, fasudil decreased AAA by 45% while significantly inhibiting
      both apoptosis and proteolysis, without affecting atherosclerosis or blood
      pressure. CONCLUSIONS: These data demonstrate that inhibition of Rho-kinase by
      fasudil attenuated Ang II-induced AAA through inhibition of both apoptosis and
      proteolysis pathways.

PMID- 15851597
TI  - Percutaneous mitral valve repair for chronic ischemic mitral regurgitation: a
      real-time three-dimensional echocardiographic study in an ovine model.
AB  - BACKGROUND: Although surgical annuloplasty is the standard repair for ischemic
      mitral regurgitation (IMR), its application is limited by high morbidity and
      mortality. Using 2D and real-time 3D echocardiography in an ovine model of
      chronic IMR, we evaluated the geometric impact and short-term efficacy of a
      percutaneous transvenous catheter-based approach for mitral valve (MV) repair
      using a novel annuloplasty device placed in the coronary sinus. METHODS AND
      RESULTS: Six sheep developed IMR 8 weeks after induced posterior myocardial
      infarction. An annuloplasty device optimized to reduce anterior-posterior (A-P)
      mitral annular dimension and MR was placed percutaneously in the coronary sinus.
      Mitral annular A-P and commissure-commissure dimensions and MV tenting area
      (MVTa) in 3 parallel A-P planes (medial, central, and lateral) were assessed by
      real-time 3D echocardiography with 3D software. The annuloplasty device reduced
      MR jet area from 5.4+/-2.6 to 1.3+/-0.9 cm2 (P<0.01), mitral annular A-P
      dimension in both systole and diastole (24.3+/-2.5 to 19.7+/-2.4 mm; P<0.03;
      31.0+/-3.9 to 24.7+/-2.1 mm; P<0.001), and MVTa at mid systole in all 3 planes
      (153+/-46 to 93+/-24 mm2, P<0.01; 140+/-47 to 88+/-23 mm2, P<0.03; and 103+/-23
      to 87+/-26 mm2, P<0.03). CONCLUSIONS: Percutaneous coronary sinus-based mitral
      annuloplasty reduces chronic IMR by reducing mitral annular A-P diameter and
      MVTa. This suggests the potential clinical application of a new nonsurgical
      therapeutic approach in patients with IMR.

PMID- 15851598
TI  - Monitoring of bone marrow cell homing into the infarcted human myocardium.
AB  - BACKGROUND: Intracoronary transfer of autologous bone marrow cells (BMCs)
      promotes recovery of left ventricular systolic function in patients with acute
      myocardial infarction. Although the mechanisms of this effect remain to be
      established, homing of BMCs into the infarcted myocardium is probably a critical
      early event. METHODS AND RESULTS: We determined BMC biodistribution after
      therapeutic application in patients with a first ST-segment-elevation myocardial
      infarction who had undergone stenting of the infarct-related artery. Unselected
      BMCs were radiolabeled with 100 MBq 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG)
      and infused into the infarct-related coronary artery (intracoronary; n=3
      patients) or injected via an antecubital vein (intravenous; n=3 patients). In 3
      additional patients, CD34-positive (CD34+) cells were immunomagnetically enriched
      from unselected BMCs, labeled with 18F-FDG, and infused intracoronarily. Cell
      transfer was performed 5 to 10 days after stenting. More than 99% of the infused
      total radioactivity was cell bound. Nucleated cell viability, comparable in all
      preparations, ranged from 92% to 96%. Fifty to 75 minutes after cell transfer,
      all patients underwent 3D PET imaging. After intracoronary transfer, 1.3% to 2.6%
      of 18F-FDG-labeled unselected BMCs were detected in the infarcted myocardium; the
      remaining activity was found primarily in liver and spleen. After intravenous
      transfer, only background activity was detected in the infarcted myocardium.
      After intracoronary transfer of 18F-FDG-labeled CD34-enriched cells, 14% to 39%
      of the total activity was detected in the infarcted myocardium. Unselected BMCs
      engrafted in the infarct center and border zone; homing of CD34-enriched cells
      was more pronounced in the border zone. CONCLUSIONS: 18F-FDG labeling and 3D PET
      imaging can be used to monitor myocardial homing and biodistribution of BMCs
      after therapeutic application in patients.

PMID- 15851599
TI  - Persistent cardiac aldosterone synthesis in angiotensin II type 1A receptor
      knockout mice after myocardial infarction.
AB  - BACKGROUND: The renin-angiotensin-aldosterone system is implicated in the
      pathogenesis of heart failure. Pharmacological blockade of angiotensin II (Ang
      II)-dependent signaling is clinically effective in reducing cardiovascular events
      after myocardial infarction (MI) but still fails to completely prevent
      remodeling. The molecular basis underlying this Ang II-independent remodeling is
      unclear. METHODS AND RESULTS: Acute MI was induced by coronary ligation in wild
      type (WT) and angiotensin II type IA receptor-knockout (AT1A-KO) mice. Left
      ventricular (LV) geometry, hemodynamics, and cardiac gene expression were
      evaluated on day 28. Severe LV remodeling and resultant cardiac dysfunction were
      observed in WT mice, whereas less marked, but still significant, LV remodeling
      and cardiac dysfunction were induced in AT1A-KO mice. Gene expression levels of
      aldosterone synthase and the cardiac aldosterone content were both elevated in
      the MI hearts, even in AT1A-KO mice. In AT1A-KO mice treated with spironolactone
      (20 mg/kg per day), LV remodeling, cardiac dysfunction, and cardiac gene
      expression of collagens and natriuretic peptides were almost normalized.
      CONCLUSIONS: Our results indicate that genetic blockade of AT1A signaling fails
      to arrest aldosterone production in cardiac tissues and that cardiac aldosterone
      plays a critical role in post-MI LV remodeling. The results suggest that
      spironolactone could be potentially effective in patients with MI, when used in
      combination with renin-angiotensin system blockade, by blocking the actions of
      aldosterone produced by Ang II-independent mechanisms.

PMID- 15851600
TI  - Regulation of bone morphogenetic protein-2 expression in endothelial cells: role
      of nuclear factor-kappaB activation by tumor necrosis factor-alpha, H2O2, and
      high intravascular pressure.
AB  - BACKGROUND: Recent studies suggest that bone morphogenetic protein-2 (BMP-2), a
      transforming growth factor-beta superfamily member cytokine, plays an important
      role both in vascular development and pathophysiological processes, including
      endothelial activation that is likely to contribute to the development of
      coronary atherosclerosis, yet the factors that regulate arterial expression of
      BMP-2 are completely unknown. We tested the hypothesis that BMP-2 expression in
      endothelial cells is governed by an H2O2 and nuclear factor (NF)-kappaBeta
      dependent pathway that can be activated by both proinflammatory and mechanical
      stimuli. METHODS AND RESULTS: The proinflammatory cytokine tumor necrosis factor
      (TNF)-alpha induced NF-kappaBeta activation and elicited significant increases in
      BMP-2 mRNA and protein in primary coronary arterial endothelial cells and human
      umbilical vein endothelial cells that were prevented by NF-kappaBeta inhibitors
      (pyrrolidine dithiocarbamate and SN-50), silencing of p65 (siRNA), or catalase.
      Administration of H2O2 also elicited NF-kappaBeta activation and BMP-2 induction.
      In organ culture, exposure of rat arteries to high pressure (160 mm Hg) elicited
      H2O2 production, nuclear translocation of NF-kappaBeta, and upregulation of BMP-2
      expression. Although high pressure upregulated TNF-alpha, it appears that it
      directly regulates BMP-2 expression, because upregulation of BMP-2 was also
      observed in vessels of TNF-alpha knockout mice. CONCLUSIONS: Vascular BMP-2
      expression can be regulated by H2O2-mediated activation of NF-kappaBeta both by
      inflammatory stimuli and by high intravascular pressure.

PMID- 15851601
TI  - Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid
      stenosis evaluated using doppler embolic signal detection: the Clopidogrel and
      Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial.
AB  - BACKGROUND: Evidence for efficacy of dual antiplatelet therapy in stroke is
      limited. Symptomatic carotid stenosis patients are at high risk of early
      recurrent stroke. In this group, asymptomatic microembolic signals (MES),
      detected by transcranial Doppler ultrasound (TCD), are markers of future stroke
      and transient ischemic attack (TIA) risk. They offer a surrogate marker to
      evaluate antiplatelet therapy, but no multicenter study has evaluated the
      feasibility of this approach. METHODS AND RESULTS: Clopidogrel and Aspirin for
      Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) is a randomized,
      double-blind study in subjects with recently symptomatic > or =50% carotid
      stenosis. Patients were screened with TCD, and if MES were detected, they were
      randomized to clopidogrel and aspirin or aspirin monotherapy. Repeated TCD
      recordings were made on days 2 and 7. MES were detected in 110 of 230 patients by
      online analysis at baseline, of whom 107 were randomized. Intention-to-treat
      analysis revealed a significant reduction in the primary end point: 43.8% of dual
      therapy patients were MES positive on day 7, as compared with 72.7% of
      monotherapy patients (relative risk reduction 39.8%; 95% CI, 13.8 to 58.0;
      P=0.0046). The secondary end point of MES frequency per hour was reduced
      (compared with baseline) by 61.4% (95% CI, 31.6 to 78.2; P=0.0013) in the dual
      therapy group at day 7 and by 61.6% (95% CI, 34.9 to 77.4; P=0.0005) on day 2.
      There were 4 recurrent strokes and 7 TIAs in the monotherapy group versus no
      stroke and 4 TIAs in the dual-therapy group that were treatment emergent and
      ipsilateral to the qualifying carotid stenosis; 2 additional ipsilateral TIAs
      occurred before treatment started. MES frequency was greater in the 17 patients
      with recurrent ipsilateral events compared with the 90 without (mean+/-SD: 24.4+/
      27.7 versus 8.9+/-11.5 per hour; P=0.0003). CONCLUSIONS: In patients with
      recently symptomatic carotid stenosis, combination therapy with clopidogrel and
      aspirin is more effective than aspirin alone in reducing asymptomatic
      embolization. Doppler MES detection is a feasible method to evaluate the efficacy
      of antiplatelet therapy in multicenter studies.

PMID- 15851602
TI  - Rise in insulin resistance is associated with escalated telomere attrition.
AB  - BACKGROUND: Insulin resistance predisposes to cardiovascular disease and shortens
      human lifespan. We therefore tested the hypothesis that a rise in insulin
      resistance in concert with gain in body mass is associated with accelerated white
      blood cell telomere attrition. METHODS AND RESULTS: We measured white blood cell
      telomere dynamics and age-related changes in insulin resistance and body mass
      index in young adults of the Bogalusa Heart Study. Over 10.1 to 12.8 years, the
      relative changes in telomere length were correlated with the homeostasis model
      assessment of insulin resistance (r=-0.531, P<0.001) and changes in the body mass
      index (r=-0.423, P<0.001). CONCLUSIONS: These findings provide the first tangible
      nexus of telomere biology with insulin resistance and adiposity in humans.

PMID- 15851603
TI  - Four-year angiographic and intravascular ultrasound follow-up of patients treated
      with sirolimus-eluting stents.
AB  - BACKGROUND: Despite the proven superiority of sirolimus-eluting stents (SESs)
      compared with bare stents in the first year after implantation, long-term
      outcomes of patients treated with these novel devices remain unknown. Our goal
      was to evaluate the clinical, angiographic, and intravascular ultrasound (IVUS)
      outcomes of patients treated with SESs 4 years after implantation. METHODS AND
      RESULTS: The study included 30 patients treated with sirolimus-eluting Bx
      Velocity stenting (slow release [SR; n=15] and fast release [FR; n=15]). Twenty
      six patients underwent 4-year angiographic and IVUS follow-up and had matched
      assessments at all time points (index and 4-, 12-, 24-, and 48-month follow-up).
      One death occurred during the study period in a patient with a patent SES. There
      were no target-vessel revascularizations or thromboses between 2- and 4-year
      follow-up examinations. There was no stent thrombosis, target-lesion
      revascularization, death, or myocardial infarction in the SR group up to 4 years.
      Cumulative event-free survival rate was 87% for the total population (80% in the
      FR group and 93% in the SR group). In-stent late loss was slightly greater in the
      FR group (0.41+/-0.49 mm) than the SR group (0.09+/-0.23) after 4 years. One
      patient in the FR group had a 52% in-stent restenosis lesion. Percent neointimal
      hyperplasia volume, as detected by IVUS, remained minimal after 4 years (FR=9.1%
      and SR=5.7%). CONCLUSIONS: This study confirms the longevity of the optimal
      outcomes observed in patients treated with sirolimus-eluting Bx Velocity stents 4
      years after implantation. In-stent lumen dimensions remained essentially
      unchanged at 4-year follow-up, particularly in the population treated with the
      currently available SES (SR formulation).

PMID- 15851604
TI  - Effects of high thoracic epidural analgesia on myocardial blood flow in patients
      with ischemic heart disease.
AB  - BACKGROUND: In patients with ischemic heart disease, high thoracic epidural
      analgesia (TEA) has been proposed to improve abnormalities of coronary function
      by inhibiting cardiac sympathetic tone. We evaluated the effect of TEA on
      myocardial blood flow in patients with ischemic heart disease. METHODS AND
      RESULTS: Twenty male patients with multivessel ischemic heart disease were
      studied. An epidural catheter was inserted between the second and third thoracic
      vertebral interspace (Th2 to Th3). Analgesia was induced by epidural injection of
      bupivacaine 0.5%, and a sensory block from the sixth cervical (C6 to C7) to Th10
      (Th8 to Th11) vertebral interspace was achieved. Myocardial blood flow was
      measured with dynamic 13N-ammonia PET with and without TEA at rest, during
      pharmacological vasodilation with dipyridamole, and during sympathetic
      stimulation with the cold pressor test. Myocardial blood flow during dipyridamole
      increased similarly, regardless of TEA, in all regions except in myocardium
      subtended by collateral arteries in which blood flow increased more with than
      without TEA (P<0.05). Without TEA, myocardial blood flow during the cold pressor
      test remained unchanged compared with myocardial blood flow at rest. In contrast,
      with TEA, myocardial blood flow increased in all vascular territories. Coronary
      vascular resistance increased during the cold pressor test without TEA, whereas
      with TEA, coronary resistance decreased in myocardium subtended by nonstenotic
      and stenotic coronary vessels and remained unchanged in myocardium subtended by
      occluded vessels. CONCLUSIONS: In patients with multivessel ischemic heart
      disease, TEA partly normalizes the myocardial blood flow response to sympathetic
      stimulation.

PMID- 15851605
TI  - Images in cardiovascular medicine. Magnetic resonance imaging findings in
      temporal arteritis.

PMID- 15851606
TI  - Images in cardiovascular medicine. No delayed enhancement on contrast magnetic
      resonance imaging with Takotsubo cardiomyopathy.

PMID- 15851607
TI  - Letter regarding article by McKechnie et al, "prognostic implication of anemia on
      in-hospital outcomes after percutaneous coronary intervention".

PMID- 15851608
TI  - Letter regarding article by Sawhney et al, "treatment of left anterior descending
      coronary artery disease with sirolimus-eluting stents".

PMID- 15851609
TI  - Surgery for hypertrophic obstructive cardiomyopathy: alive and quite well.

PMID- 15851610
TI  - Clopidogrel pretreatment for percutaneous coronary intervention: double, double,
      dose in trouble?

PMID- 15851611
TI  - Tetrahydrobiopterin in pulmonary hypertension: pulmonary hypertension in
      guanosine triphosphate-cyclohydrolase-deficient mice.

PMID- 15851612
TI  - Defective cardiac ryanodine receptor regulation during atrial fibrillation.
AB  - BACKGROUND: Ca2+ leak from the sarcoplasmic reticulum (SR) may play an important
      role in triggering and/or maintaining atrial arrhythmias, including atrial
      fibrillation (AF). Protein kinase A (PKA) hyperphosphorylation of the cardiac
      ryanodine receptor (RyR2) resulting in dissociation of the channel-stabilizing
      subunit calstabin2 (FK506-binding protein or FKBP12.6) causes SR Ca2+ leak in
      failing hearts and can trigger fatal ventricular arrhythmias. Little is known
      about the role of RyR2 dysfunction in AF, however. METHODS AND RESULTS: Left and
      right atrial tissue was obtained from dogs with AF induced by rapid right atrial
      pacing (n=6 for left atrial, n=4 for right atrial) and sham instrumented controls
      (n=6 for left atrial, n=4 for right atrial). Right atrial tissue was also
      collected from humans with AF (n=10) and sinus rhythm (n=10) and normal cardiac
      function. PKA phosphorylation of immunoprecipitated RyR2 was determined by back
      phosphorylation and by immunoblotting with a phosphospecific antibody. The amount
      of calstabin2 bound to RyR2 was determined by coimmunoprecipitation. RyR2 channel
      currents were measured in planar lipid bilayers. Atrial tissue from both the AF
      dogs and humans with chronic AF showed a significant increase in PKA
      phosphorylation of RyR2, with a corresponding decrease in calstabin2 binding to
      the channel. Channels isolated from dogs with AF exhibited increased open
      probability under conditions simulating diastole compared with channels from
      control hearts, suggesting that these AF channels could predispose to a diastolic
      SR Ca2+ leak. CONCLUSIONS: SR Ca2+ leak due to RyR2 PKA hyperphosphorylation may
      play a role in initiation and/or maintenance of AF.

PMID- 15851613
TI  - Pregnancy-associated cardiomyopathy: clinical characteristics and a comparison
      between early and late presentation.
AB  - BACKGROUND: Cardiomyopathy associated with pregnancy was first described more
      than half a century ago. However, because of its rare occurrence and geographical
      differences, the clinical profile of this condition has remained incompletely
      defined. METHODS AND RESULTS: Data obtained from 123 women with a history of
      cardiomyopathy diagnosed during pregnancy or the postpartum period were reviewed.
      One hundred women met traditional criteria of peripartum cardiomyopathy; 23 were
      diagnosed with pregnancy-associated cardiomyopathy earlier than the last
      gestational month. Peripartum cardiomyopathy patients had a mean age of 31+/-6
      years and were mostly white (67%). Common associated conditions were gestational
      hypertension (43%), tocolytic therapy (19%), and twin pregnancy (13%). Left
      ventricular ejection fraction at the time of diagnosis was 29+/-11% and improved
      to 46+/-14% (P< or =0.0001) at follow-up. Normalization of left ventricular
      ejection fraction occurred in 54% and was more likely in patients with left
      ventricular ejection fraction >30% at diagnosis. Maternal mortality was 9%. A
      comparison between the peripartum cardiomyopathy and early pregnancy-associated
      cardiomyopathy groups revealed no differences in age, race, associated
      conditions, left ventricular ejection fraction at diagnosis, its rate and time of
      recovery, and maternal outcome. CONCLUSIONS: This study helps to define the
      clinical profile of patients with pregnancy-associated cardiomyopathy diagnosed
      in the United States. Clinical presentation and outcome of patients with
      pregnancy-associated cardiomyopathy diagnosed early in pregnancy are similar to
      those of patients with traditional peripartum cardiomyopathy. These 2 conditions
      may represent a continuum of a spectrum of the same disease.

PMID- 15851614
TI  - The capsaicin-sensitive afferent neuron in skeletal muscle is abnormal in heart
      failure.
AB  - BACKGROUND: In heart failure, the cardiovascular response to activation of the
      skeletal muscle exercise pressor reflex (EPR) is exaggerated. Group IV afferent
      neurons, primarily stimulated by the metabolic by-products of skeletal muscle
      work, contribute significantly to the EPR. Therefore, it was postulated that
      alterations in the activity of group IV neurons contribute to the EPR dysfunction
      manifest in heart failure. METHODS AND RESULTS: Group IV afferent fibers were
      ablated in neonatal Sprague-Dawley rats by subcutaneous administration of
      capsaicin. In neonatal capsaicin-treated adult animals, selective activation of
      the EPR, by electrically induced static muscle contraction, recapitulated the
      exaggerated increases in heart rate and blood pressure observed in rats with
      dilated cardiomyopathy (DCM). Furthermore, compared with control animals, both
      neonatal capsaicin-treated and DCM rats displayed a decreased pressor response to
      the intra-arterial administration of capsaicin within the hindlimb, a maneuver
      that selectively excites group IV afferent neurons. Moreover, expression of mRNA
      for the capsaicin receptor TRPv1, a marker of group IV fibers, was downregulated
      in DCM animals compared with controls. CONCLUSIONS: These findings suggest that
      EPR dysfunction in heart failure results in part from functional and molecular
      alterations in group IV fibers. Furthermore, the responsiveness of these
      metabolically sensitive neurons appears to be blunted in DCM, indicating that
      their contribution to the EPR may be reduced. This occurs despite an overall
      exaggeration of the EPR in heart failure. These insights into the basic
      mechanisms of EPR dysfunction are essential to the development of effective
      therapeutic strategies aimed at improving exercise capacity in heart failure.

PMID- 15851615
TI  - Progressive attenuation of myocardial vascular endothelial growth factor
      expression is a seminal event in diabetic cardiomyopathy: restoration of
      microvascular homeostasis and recovery of cardiac function in diabetic
      cardiomyopathy after replenishment of local vascular endothelial growth factor.
AB  - BACKGROUND: Diabetic cardiomyopathy (DCM) is characterized by microvascular
      pathology and interstitial fibrosis, which leads to progressive heart failure;
      however, the pathogenesis of DCM remains uncertain. METHODS AND RESULTS: Using
      the streptozotocin-induced diabetic rat model, we evaluated the natural course of
      DCM over a period of 1 year by serial echocardiography, Western blot analysis for
      vascular endothelial growth factor (VEGF), endothelial progenitor cell assays,
      myocardial blood flow measurements, and histopathologic analysis that included
      terminal dUTP nick end-labeling (TUNEL), capillary and cardiomyocyte density, and
      fibrosis area. Downregulation of myocardial VEGF expression preceded all other
      features of DCM and was followed by increased apoptosis of endothelial cells,
      decreased numbers of circulating endothelial progenitor cells, decreased
      capillary density, and impaired myocardial perfusion. Apoptosis and necrosis of
      cardiomyocytes ensued, along with fibrosis and progressive diastolic and then
      systolic dysfunction. To provide further evidence of the central role of VEGF in
      the pathophysiology of DCM, we replenished myocardial VEGF expression using naked
      DNA gene therapy via direct intramyocardial injection of plasmid DNA encoding
      VEGF (phVEGF165). VEGF-replenished rats showed increased capillary density,
      decreased endothelial cell and cardiomyocyte apoptosis, and in situ
      differentiation of bone marrow-derived endothelial progenitor cells into
      endothelial cells. These anatomic findings were accompanied by significant
      improvements in cardiac function. CONCLUSIONS: These findings suggest that
      downregulation of VEGF may compromise microvascular homeostasis in the myocardium
      and thereby play a central role in the pathogenesis of DCM.

PMID- 15851616
TI  - Late gadolinium enhancement cardiovascular magnetic resonance of the systemic
      right ventricle in adults with previous atrial redirection surgery for
      transposition of the great arteries.
AB  - BACKGROUND: Patients treated for transposition of the great arteries by atrial
      redirection surgery have a right ventricle (RV) that sustains systemic pressures
      long term. Late RV dysfunction occurs in these patients; the reasons for this are
      unclear, but myocardial fibrosis may be important. Myocardial fibrosis can be
      visualized by late gadolinium enhancement (LGE) cardiovascular magnetic resonance
      (CMR). We hypothesized that LGE would be present in the systemic RV and relate to
      adverse clinical features. METHODS AND RESULTS: We performed CMR on 36
      consecutive adult patients (mean age, 27 years) after atrial redirection surgery
      for transposition of the great arteries. Late gadolinium RV enhancement was seen
      in 22 patients (61%) with various patterns. Patients with RV LGE were older (30
      versus 22 years; P<0.001) and had increased RV end-systolic volume index (43
      versus 35 mL/m2; P=0.03), decreased RV ejection fraction (57% versus 62%;
      P=0.02), increased QRS duration (108 versus 97 ms; P=0.01), and increased QT
      dispersion (93 versus 71 ms; P=0.002). The extent of LGE correlated with age
      (r=0.59, P<0.001) and QRS duration (r=0.67, P<0.001) and inversely with RV
      ejection fraction (r=-0.76, P<0.001). The incidence of documented arrhythmia
      and/or syncope (10 of 36) was significantly higher in the late gadolinium
      positive group (9/22 versus 1/14; P=0.03). CONCLUSIONS: LGE CMR suggestive of
      myocardial fibrosis occurs in the systemic RV of patients after atrial
      redirection surgery. The extent of LGE correlates with age, ventricular
      dysfunction, electrophysiological parameters, and clinical events, suggesting
      prognostic importance that merits further investigation.

PMID- 15851617
TI  - Effectiveness and safety of sirolimus-eluting stents in the treatment of
      restenosis after coronary stent placement.
AB  - BACKGROUND: In-stent restenosis is notoriously difficult to treat by repeat
      catheter intervention because of its propensity for aggressive recurrent
      neointimal formation. This study sought to assess the effectiveness and safety of
      the sirolimus-eluting stent in the treatment of in-stent restenosis. METHODS AND
      RESULTS: The study was designed as a prospective multicenter registry. We
      included 162 patients with in-stent restenosis of a native coronary artery who
      had a clinical indication for repeat intervention. Patients were scheduled for
      follow-up angiography at 6 months. The primary end point was in-lesion late loss.
      Follow-up angiography was performed in 155 patients. We obtained an in-lesion
      late loss of 0.08+/-0.49 mm and a binary restenosis rate of 9.7% (15/155), which
      prompted reintervention in 7.4% (12/162) at 9 months. The 9-month rate of death
      was 1.2% (2/162) and that of nonfatal myocardial infarction was 1.2% (2/162).
      CONCLUSIONS: Sirolimus-eluting stents were highly efficacious and safe in the
      treatment of in-stent restenosis. Our study provides rationale for the use of
      sirolimus-eluting stents in the treatment of in-stent restenosis.

PMID- 15851618
TI  - Hyperhomocysteinemia, a cardiac metabolic disease: role of nitric oxide and the
      p22phox subunit of NADPH oxidase.
AB  - BACKGROUND: Hyperhomocysteinemia (HHcy) is a reliable indicator of cardiovascular
      disease, in part because of the production of superoxide and scavenging of nitric
      oxide (NO). The present study assessed the impact of HHcy on the NO-dependent
      control of cardiac O2 consumption and examined enzymatic sources of superoxide.
      METHODS AND RESULTS: Rats and mice were fed methionine in drinking water for 5 to
      9 weeks to increase plasma homocysteine, a process that did not cause significant
      changes in hemodynamic function. The ability of the NO agonists bradykinin and
      carbachol to reduce myocardial O2 consumption in vitro was impaired by
      approximately 40% in methionine-fed rats, and this impairment was proportional to
      their individual plasma homocysteine concentration. However, responses were
      restored in the presence of ascorbic acid, tempol, and apocynin, which inhibits
      NADPH oxidase assembly. Western blots showed no difference in Cu/Zn or Mn
      superoxide dismutase, endothelial NO synthase, or inducible NO synthase protein,
      but HHcy caused a 100% increase in the p22phox subunit of NADPH oxidase. Western
      blots with plasma membrane-enriched fractions of cell lysate detected elevated
      levels of p22phox, p67phox, and rac-1, which indicates increased oxidase
      assembly. Finally, mice lacking a functional gp91phox subunit of NADPH oxidase
      demonstrated normal NO-dependent regulation of myocardial O2 consumption after
      methionine feeding. CONCLUSIONS: In HHcy, superoxide produced by NADPH oxidase
      reduces the ability of NO to regulate mitochondrial function in the myocardium.
      The severity of this effect is proportional to the increase in homocysteine.

PMID- 15851619
TI  - Arterial hemodynamics in patients after Kawasaki disease.
AB  - BACKGROUND: Histopathological findings in the acute stage of Kawasaki disease
      (KD) indicate widespread vascular inflammation that involves not only coronary
      arteries but also systemic arteries. This may cause changes in systemic arterial
      wall properties after KD, which could have adverse effects on arterial
      hemodynamics (an important predictor of cardiovascular morbidity and mortality).
      METHODS AND RESULTS: Systemic arterial hemodynamics were investigated by
      measuring aortic input impedance during cardiac catheterization in 42 KD patients
      who had developed coronary artery lesions (CALs) in the acute stage of KD. The KD
      patients were subdivided into 2 groups according to the angiographic findings
      (group 1A, 26 patients with persistent CALs; group 1B, 16 patients with regressed
      CALs), and results were compared with those of 36 referents (group 2). Compared
      with referents, characteristic impedance was significantly higher for KD patients
      (137.0+/-5.1, 125.7+/-8.2, and 97.9+/-4.1 dyne x s x cm(-5) x m2 for group 1A,
      group 1B, and group 2, respectively), and total peripheral arterial compliance
      indexed to age-specific values was significantly lower for KD patients (group 1A
      72.9+/-4.2% of normal; group 1B 70.6+/-5.9% of normal; group 2 97.7+/-4.0% of
      normal; for both variables, P<0.05 for each KD group versus group 2; P=NS between
      KD groups), which suggests that both central and peripheral arterial wall
      stiffness increase after KD regardless of persistence of CALs. Also, indices of
      arterial wave reflection (reflection coefficient, reflection factor, and
      augmentation index) were all significantly higher in KD patients than in
      referents (P<0.05), with the result that the aortic pressure waveforms of the
      present KD patients resembled those generally observed in the elderly. In
      addition, levels of circulating markers of endothelial dysfunction (ACE and von
      Willebrand factor) were associated with increased vascular stiffening in KD
      patients but not in referents. CONCLUSIONS: These results indicating abnormal
      arterial hemodynamics after KD highlight the importance of regular monitoring of
      the systemic arterial bed and potentially relevant cardiovascular events in long
      term follow-up of KD.

PMID- 15851620
TI  - Cardiocerebral resuscitation: the new cardiopulmonary resuscitation.

PMID- 15851621
TI  - Report from the meeting of the Circulatory System Devices Panel of the Food and
      Drug Administration Center for Devices and Radiologic Health: September 21, 2004.

PMID- 15851622
TI  - Patient selection for cardiac resynchronization therapy: from the Council on
      Clinical Cardiology Subcommittee on Electrocardiography and Arrhythmias and the
      Quality of Care and Outcomes Research Interdisciplinary Working Group, in
      collaboration with the Heart Rhythm Society.
AB  - Cardiac resynchronization therapy (CRT) is a relatively new therapy for patients
      with symptomatic heart failure resulting from systolic dysfunction. CRT is
      achieved by simultaneously pacing both the left and right ventricles.
      Biventricular pacing resynchronizes the timing of global left ventricular
      depolarization and improves mechanical contractility and mitral regurgitation.
      Published clinical trials have demonstrated that CRT results in improved clinical
      status and lower mortality rate when selected patients with systolic ventricular
      dysfunction and heart failure are treated with CRT. This advisory identifies
      appropriate candidates for CRT on the basis of the inclusion criteria and results
      from the published clinical trials.

PMID- 15851624
TI  - Quantitative coronary angiogram analysis: nifedipine retard versus angiotensin
      converting enzyme inhibitors (JMIC-B side arm study).
AB  - This study was performed to compare the effects of nifedipine retard and
      angiotensin-converting enzyme (ACE) inhibitors on the progression of coronary
      atherosclerosis by means of quantitative coronary angiogram. Coronary angiogram
      was performed before the start of the study and during the 3-year treatment
      period. This study was conducted on the assumption that possible coronary
      vasodilation, which may be caused by nifedipine, was excluded by administration
      of sufficient isosorbide dinitrate. The changes from the baseline in the minimum
      lumen diameter of the coronary artery in all measured segments were negligible in
      the nifedipine group (+0.02+/-0.27 mm; P=0.543), whereas they were significantly
      reduced in the ACE inhibitor group (-0.12+/-0.27 mm; P<0.001), with a significant
      difference observed between the groups (P=0.002). The number of progressors in
      the nifedipine group was significantly lower than that in the ACE inhibitor group
      (P=0.019), and there was also a significant difference between the groups in the
      number of patients in whom > or =1 lesion developed after treatment (P=0.040).
      However, the changes of minimum lumen diameter stratified by baseline percent
      diameter stenosis demonstrated that progression of coronary atherosclerosis was
      suppressed in the nifedipine group for lesions with a percent diameter stenosis
      of < or =40 but was suppressed in both groups for those with a percent diameter
      stenosis of > or =41. This study suggests that nifedipine retard and ACE
      inhibitors may be effective in suppression of progression of coronary
      atherosclerosis, and that nifedipine in particular may be effective for mild to
      moderate stenosis.

PMID- 15851625
TI  - Structural and genetic bases of arterial stiffness.
AB  - Arterial stiffness has independent predictive value for cardiovascular events. We
      review data concerning the heritability of arterial stiffness, and propose an
      integrated view of the structural and genetic determinants of arterial stiffness,
      based on a candidate gene approach and recent studies on gene expression profile.
      Arterial stiffness seems to have a genetic component, which is largely
      independent of the influence of blood pressure and other cardiovascular risk
      factors. In animal models of essential hypertension (SHR and SHR-SP), structural
      modifications of the arterial wall include an increase in the number of
      elastin/smooth muscle cell (SMC) connections, and smaller fenestrations of the
      internal elastic lamina, possibly leading to redistribution of the mechanical
      load toward elastic materials. These modifications may give rise to mechanisms
      that explain why changes in arterial wall material accompanying wall hypertrophy
      in these animals are not associated with an increase in arterial stiffness. In
      monogenic connective tissue diseases (Marfan, Williams, and Ehlers-Danlos
      syndromes) and the corresponding animal models, precise characterization of the
      arterial phenotype makes it possible to determine the influence of abnormal
      genetically determined wall components on arterial stiffness. Such studies have
      highlighted the role of extracellular matrix signaling in the vascular wall and
      have shown that elastin and collagen not only display elasticity or rigidity but
      also are involved in the control of SMC function. These data provide strong
      evidence that arterial stiffness is affected by the amount and density of stiff
      wall material and the spatial organization of that material.

PMID- 15851626
TI  - Control of hypertension in adults with chronic kidney disease in the United
      States.
AB  - Although improved control of hypertension is known to attenuate progression of
      chronic kidney disease (CKD), little is known about the adequacy of hypertension
      treatment in adults with CKD in the United States. Using data from the Fourth
      National Health and Nutrition Survey, we assessed adherence to national
      hypertension guideline targets for patients with CKD (blood pressure <130/80 mm
      Hg), we assessed control of systolic (<130 mm Hg) and diastolic (<80 mm Hg) blood
      pressure, and we evaluated determinants of adequate blood pressure control.
      Presence of CKD was defined as glomerular filtration rate <60 mL/min per 1.73 m2
      or presence of albuminuria (albumin:creatinine ratio >30 microg/mg).
      Multivariable logistic regression with appropriate weights was used to determine
      predictors of inadequate hypertension control and related outcomes. Among 3213
      participants with CKD, 37% had blood pressure <130/80 mm Hg (95% confidence
      interval [CI], 34.5% to 41.8%). Of those with inadequate blood pressure control,
      59% (95% CI, 54% to 64%) had systolic >130 mm Hg, with diastolic < or =80 mm Hg,
      whereas only 7% (95% CI, 3.9 to 9.8%) had a diastolic pressure >80 mm Hg, with
      systolic blood pressure < or =130 mm Hg. Non-Hispanic black race (odds ratio
      [OR], 2.4; 95% CI, 1.5 to 3.9), age >75 years (OR, 4.7; 95% CI, 2.7 to 8.2), and
      albuminuria (OR, 2.4; 95% CI, 1.4 to 4.1) were independently associated with
      inadequate blood pressure control. We conclude that control of hypertension is
      poor in participants with CKD and that lack of control is primarily attributable
      to systolic hypertension. Future guidelines and antihypertensive therapies for
      patients with CKD should target isolated systolic hypertension.

PMID- 15851627
TI  - Progression of coronary artery calcium and occurrence of myocardial infarction in
      patients with and without diabetes mellitus.
AB  - Progression of coronary artery calcium, a marker of atherosclerosis, can be
      slowed with statins, and continued progression of calcium is associated with an
      increased risk of myocardial infarction. However, it is not known whether statins
      are effective in slowing calcium progression in diabetes mellitus. In a
      retrospective study, we examined 1153 nondiabetic and 157 diabetic subjects who
      underwent sequential electron beam tomography scans at a minimum 1-year interval
      to assess progression of coronary calcium. A yearly score increase >15% was
      considered evidence of true progression. The use of statins and occurrence of
      myocardial infarction were recorded. There was no difference in baseline calcium
      score between diabetic and nondiabetic patients. Diabetic patients with no
      coronary calcium on the baseline scans developed it more often than nondiabetic
      subjects (42% versus 25%; P=0.046) during follow-up. Calcium progression was 33%
      greater in diabetic patients than nondiabetic subjects (P<0.001) if no statin
      therapy was provided and 17.7% greater when statins were used (P<0.001). Among
      the 49 subjects who experienced a myocardial infarction, the calcium score
      increased on average 20% more in diabetic than nondiabetic patients (P<0.001). In
      logistic models, diabetes mellitus and systemic hypertension were the best
      predictors of calcium progression (odds ratio, 3.1 and 1.9, respectively),
      whereas baseline calcium score percentile and statin therapy were the best
      predictors of infarction. These findings support the notion that diabetes
      mellitus causes accelerated atherosclerosis, even in the presence of statin
      therapy, and provide evidence that coronary calcium monitoring is an effective
      method to assess treatment efficacy.

PMID- 15851628
TI  - Advanced glycation end products are associated with pulse pressure in type 1
      diabetes: the EURODIAB Prospective Complications Study.
AB  - We investigated the associations of pulse pressure (a measure of arterial
      stiffness) with the early glycation products hemoglobin A1c (HbA1c) and Amadori
      albumin and the advanced glycation end products pentosidine, Nepsilon
      (carboxymethyl)lysine and Nepsilon-(carboxyethyl)lysine in a large group of type
      1 diabetic individuals of the EURODIAB Prospective Complications Study. We did a
      cross-sectional nested case-control study from the EURODIAB Prospective
      Complications Study of 543 (278 men) European individuals with type 1 diabetes
      diagnosed at <36 years of age. We used linear regression analyses to investigate
      the association of pulse pressure with glycation products. Pulse pressure was
      significantly associated with plasma levels of Nepsilon-(carboxymethyl)lysine and
      Nepsilon-(carboxyethyl)lysine but not with HbA1c, Amadori albumin, and urinary
      levels of pentosidine. Regression coefficients adjusted for age, sex, mean
      arterial pressure, and duration of diabetes were 0.09 mm Hg (P=0.003) per 1
      microM/M lysine Nepsilon-(carboxymethyl)lysine; 0.24 mm Hg (P=0.001) and -0.03 mm
      Hg (P=0.62) per 1 microM/M lysine Nepsilon-(carboxyethyl)lysine (in individuals
      with and without complications, respectively; P interaction=0.002); and 0.50 mm
      Hg (P=0.16) per 1% HbA1c; 0.07 mm Hg (P=0.12) per 1 U/mL Amadori albumin; and
      0.77 mm Hg (P=0.48) per 1 nmol/mmol creatinine pentosidine. In young type 1
      diabetic individuals, arterial stiffness is strongly associated with the advanced
      glycation end products Nepsilon-(carboxymethyl)lysine and Nepsilon
      (carboxyethyl)lysine. These findings suggest that the formation of advanced
      glycation end products is an important pathway in the development of arterial
      stiffness in young type 1 diabetic individuals.

PMID- 15851629
TI  - Hypertension management in the elderly has improved: Ontario prescribing trends,
      1994 to 2002.
AB  - To examine whether the treatment of elderly hypertensives had become more
      aggressive over the past decade, we evaluated: (1) the frequency of new
      prescriptions for hypertension treatment, adjusted by age and gender; (2) the
      frequency with which multiple antihypertensives were prescribed concurrently
      within 2 years of initial diagnosis; and (3) discontinuation rates for
      antihypertensive therapy. We linked 4 administrative databases and a province
      wide clinical database in Ontario, Canada, to derive a cohort of patients > or
      =66 years of age who were newly started on an antihypertensive agent between July
      1, 1994, and March 31, 2002, without another indication for the agent (all
      patients were followed for 2 years after their initial antihypertensive
      prescription). Our cohort consisted of 196 451 people newly started on
      antihypertensive therapy, 30 433 of whom also had diabetes mellitus. The
      population-adjusted rate of new antihypertensive prescriptions increased by 30%
      between 1994 and 2002. Whereas 21% of patients newly diagnosed with hypertension
      in 1994 were prescribed multiple antihypertensives concurrently within 2 years of
      diagnosis, this proportion had increased to 40% by 2002 (P<0.0001). In the cohort
      of patients first prescribed an antihypertensive in 1994, 36% were not taking any
      antihypertensive within 2 years; only 21% of patients first prescribed an
      antihypertensive in 2002 had discontinued all therapy within 2 years (P<0.0001).
      Our data provide evidence that the physician management of hypertension in
      elderly Canadians became more aggressive between 1994 and 2002.

PMID- 15851630
TI  - Cyclooxygenase-2 inhibitors attenuate angiotensin II-induced oxidative stress,
      hypertension, and cardiac hypertrophy in rats.
AB  - Angiotensin II is an important oxidative stress mediator. Our previous studies
      have indicated that the potent antioxidative properties of acetylsalicylic acid
      play an important role in its cardiovascular protective effects. There are some
      ongoing controversies concerning the use of selective cyclooxygenase-2 inhibitors
      in cardiovascular disease. The aim of this study was to determine whether the
      cyclooxygenase-2 selective inhibitors rofecoxib and nimesulide possess
      antioxidative and cardiovascular protective effects against angiotensin II.
      Chronic subcutaneous angiotensin II infusion increased cardiovascular but not
      colonic tissue superoxide production, heart/body weight ratio, and blood
      pressure. Moreover, angiotensin II selectively increased cardiac cyclooxygenase-2
      but not cyclooxygenase-1 expression, which was totally prevented by
      acetylsalicylic acid treatment. Similar to acetylsalicylic acid, rofecoxib or
      nimesulide treatments significantly attenuated angiotensin II-induced oxidative
      stress, hypertension, and cardiac NAD(P)H oxidase subunit p47(phox) expression.
      Rofecoxib also reduced cardiac hypertrophy. Treatment with nonselective anti
      inflammatory drugs ibuprofen, indomethacin, or salicylic acid did not show any
      effect on angiotensin II-induced superoxide production, hypertension, or cardiac
      hypertrophy. Although acetylsalicylic acid and salicylic acid inhibited
      angiotensin II-induced nuclear factor kappaB (NF-kappaB) activation, nimesulide
      did not modify NF-kappaB activation. In conclusion, cyclooxygenase-2 pathway is
      implicated in angiotensin II-induced oxidative stress and deleterious
      cardiovascular changes. Rofecoxib and nimesulide produced significant
      antioxidative effect by reducing NAD(P)H oxidase-dependent superoxide generation.
      These effects seem to be independent of NF-kappaB inhibition.

PMID- 15851631
TI  - Thyrotoxicosis caused by weight-reducing herbal medicines.
AB  - The weight-reducing herbal medicines "Dream Shape" and "Ever Youth" became
      available in Japan in 2000. Herein, we describe 12 patients who developed
      thyrotoxicosis after taking them. The thyroid hormone content of 1 capsule or
      tablet of herbal medicine, measured following Pronase digestion and ethanol
      extraction, was approximately 1 mug of triiodothyronine and 3 to 4 mug of
      thyroxine. Two of us took 10 capsules or tablets of Dream Shape or Ever Youth,
      and changes in thyroid hormone levels were observed during the first 24 hours.
      Serum free triiodothyronine levels began to rise 2 hours after ingestion and
      reached peak levels at 4 to 8 hours; changes in free thyroxine and thyrotropin
      levels were small during the first 24 hours. Similar herbal medicines may have
      been distributed to other countries via the Internet. Resultant factitious
      thyrotoxicosis can create diagnostic and therapeutic confusion, particularly in
      patients with thyroid disease.

PMID- 15851632
TI  - Business as usual.

PMID- 15851633
TI  - Reducing the amount of blood transfused: a systematic review of behavioral
      interventions to change physicians' transfusion practices.
AB  - BACKGROUND: Transfusion services have used various techniques to reduce blood
      product utilization. Given the potential adverse effects of transfusions and the
      resources consumed in implementing strategies to reduce transfusions, there is a
      need to understand their effectiveness. Therefore, we performed a systematic
      review of the literature to examine the effectiveness of behavioral interventions
      to reduce blood product utilization. METHODS: We identified all relevant articles
      through the use of electronic searches of MEDLINE and EMBASE, as well as hand
      searches of review articles and personal files. The electronic searches included
      articles published between January 1966 and May 2003. The searches included the
      terms blood transfusion, plasma exchange, guidelines, education, practice
      patterns, and professional practice. The outcomes of interest were the number of
      units transfused and the proportion of patients who received transfusions.
      RESULTS: Nineteen studies examining the effectiveness of single (guidelines,
      prospective audits, retrospective audits, and reminders) or multifaceted
      interventions in reducing red blood cell, platelet, plasma, cryoprecipitate, and
      albumin transfusions met the inclusion criteria. Eighteen studies demonstrated a
      relative reduction in the number of units given (range, 9%-77%) or the proportion
      of patients receiving transfusions (range, 17%-79%). The reported reductions were
      qualitatively similar for the different blood products studied. No particular
      intervention or combination of interventions appeared more effective in reducing
      utilization. CONCLUSIONS: Behavioral interventions, including simple
      interventions, appear to be effective in changing physician transfusion practices
      and reducing blood utilization. Appropriately designed clinical trials are still
      needed to determine the relative effectiveness of different interventions to
      change practices.

PMID- 15851634
TI  - Healthy lifestyle characteristics among adults in the United States, 2000.
AB  - BACKGROUND: Many public health recommendations and clinical guidelines emphasize
      the importance of healthy lifestyles. Recent epidemiologic studies demonstrate
      that following a healthy lifestyle has substantial health benefits. The
      objectives of this study were to report on the prevalence of healthy lifestyle
      characteristics (HLCs) and to generate a single indicator of a healthy lifestyle.
      METHODS: National data for the year 2000 were obtained from the Behavioral Risk
      Factor Surveillance System, which consists of annual, statewide, random digit
      dialed household telephone surveys. We defined the following 4 HLCs: nonsmoking,
      healthy weight (body mass index [calculated as weight in kilograms divided by the
      square of height in meters] of 18.5-25.0), consuming 5 or more fruits and
      vegetables per day, and regular physical activity (> or =30 minutes for > or =5
      times per week). The 4 HLCs were summed to create a healthy lifestyle index
      (range, 0-4), and the pattern of following all 4 HLCs was defined as a single
      healthy lifestyle indicator. We report prevalences of each HLC and the indicator
      by major demographic subgroups. RESULTS: By using data from more than 153 000
      adults, the prevalence (95% confidence interval) of the individual HLCs was as
      follows: nonsmoking, 76.0% (75.6%-76.4%); healthy weight, 40.1% (39.7%-40.5%); 5
      fruits and vegetables per day, 23.3% (22.9%-23.7%); and regular physical
      activity, 22.2% (21.8%-22.6%). The overall prevalence of the healthy lifestyle
      indicator (ie, having all 4 HLCs) was only 3.0% (95% confidence interval, 2.8%
      3.2%), with little variation among subgroups (range, 0.8%-5.7%). CONCLUSION:
      These data illustrate that a healthy lifestyle-defined as a combination of 4 HLCs
      was undertaken by very few adults in the United States, and that no subgroup
      followed this combination to a level remotely consistent with clinical or public
      health recommendations.

PMID- 15851635
TI  - Angiotensin-converting enzyme inhibitors and change in aortic valve calcium.
AB  - BACKGROUND: Calcium accumulation in the aortic valve is a hallmark of aortic
      sclerosis and aortic stenosis. Because lipoproteins, angiotensin-converting
      enzyme, and angiotensin II colocalize with calcium in aortic valve lesions, we
      hypothesized an association between angiotensin-converting enzyme inhibitor
      (ACEI) use and lowered aortic valve calcium (AVC) accumulation, as measured by
      electron beam computed tomography. METHODS: Rates of change in volumetric AVC
      scores were determined retrospectively for 123 patients who had undergone 2
      serial electron beam computed tomographic scans. The mean (+/-SD) interscan
      interval was 2.5 (+/-1.7) years; 80 patients did not receive ACEIs and 43
      received ACEIs. The relationship of ACEI use to median rates of AVC score change
      (both unadjusted and adjusted for baseline AVC scores and coronary heart disease
      risk factors) was determined. We also examined the relationship of ACEI use to
      the likelihood of and adjusted odds ratio for definite progression (AVC change >2
      times the median interscan variability). RESULTS: Unadjusted and adjusted median
      rates of AVC score change were significantly higher in the no-ACEI group than in
      the ACEI group (adjusted median AVC changes [95% confidence interval]: relative,
      28.7%/y [18.9%-38.5%/y] vs 11.0%/y [-1.9% to 24.0%/y], P = .04; absolute: 25.1/y
      [19.7-30.5/y] vs 12.2/y [4.5-19.9/y], P = .02). The adjusted odds ratio (95%
      confidence interval) for definite AVC progression was significantly lower for
      patients who received ACEIs (0.29 [0.11-0.75], P = .01). CONCLUSIONS: This
      retrospective study finds a significant association between ACEI use and a lower
      rate of AVC accumulation. The results support the need for prospective,
      randomized trials of ACEIs in calcific aortic valve disease.

PMID- 15851636
TI  - Association of sleep time with diabetes mellitus and impaired glucose tolerance.
AB  - BACKGROUND: Experimental sleep restriction causes impaired glucose tolerance
      (IGT); however, little is known about the metabolic effects of habitual sleep
      restriction. We assessed the cross-sectional relation of usual sleep time to
      diabetes mellitus (DM) and IGT among participants in the Sleep Heart Health
      Study, a community-based prospective study of the cardiovascular consequences of
      sleep-disordered breathing. METHODS: Participants were 722 men and 764 women,
      aged 53 to 93 years. Usual sleep time was obtained by standardized questionnaire.
      Diabetes mellitus was defined as a serum glucose level of 126 mg/dL or more (> or
      =7.0 mmol/L) fasting or 200 mg/dL or more (> or =11.1 mmol/L) 2 hours following
      standard oral glucose challenge or medication use for DM. Impaired glucose
      tolerance was defined as a 2-hour postchallenge glucose level of 140 mg/dL or
      more (> or =7.8 mmol/L) and less than 200 mg/dL. The relation of sleep time to DM
      and IGT was examined using categorical logistic regression with adjustment for
      age, sex, race, body habitus, and apnea-hypopnea index. RESULTS: The median sleep
      time was 7 hours per night, with 27.1% of subjects sleeping 6 hours or less per
      night. Compared with those sleeping 7 to 8 hours per night, subjects sleeping 5
      hours or less and 6 hours per night had adjusted odds ratios for DM of 2.51 (95%
      confidence interval, 1.57-4.02) and 1.66 (95% confidence interval, 1.15-2.39),
      respectively. Adjusted odds ratios for IGT were 1.33 (95% confidence interval,
      0.83-2.15) and 1.58 (95% confidence interval, 1.15-2.18), respectively. Subjects
      sleeping 9 hours or more per night also had increased odds ratios for DM and IGT.
      These associations persisted when subjects with insomnia symptoms were excluded.
      CONCLUSIONS: A sleep duration of 6 hours or less or 9 hours or more is associated
      with increased prevalence of DM and IGT. Because this effect was present in
      subjects without insomnia, voluntary sleep restriction may contribute to the
      large public health burden of DM.

PMID- 15851637
TI  - Population-based drug-induced agranulocytosis.
AB  - BACKGROUND: Since the publication of a major international case-control study on
      the risk of agranulocytosis associated with the use of medicines in the 1980s,
      many new drugs have been introduced in therapeutics. METHODS: Seventeen units of
      hematology contribute to the case-control surveillance of agranulocytosis and
      aplastic anemia in Barcelona, Spain. After a follow-up of 78.73 million person
      years, 177 community cases of agranulocytosis were compared with 586 sex-, age,
      and hospital-matched control subjects with regard to previous use of medicines.
      RESULTS: The annual incidence of community-acquired agranulocytosis was 3.46:1
      million, and it increased with age. The fatality rate was 7.0%, and the mortality
      rate was 0.24:1 million. The drug most strongly associated with a risk of
      agranulocytosis was ticlopidine hydrochloride with an odds ratio (OR) of 103.23
      (95% confidence interval [CI], 12.73-837.44), followed by calcium dobesilate (OR,
      77.84 [95% CI, 4.50-1346.20]), antithyroid drugs (OR, 52.75 [95% CI, 5.82
      478.03]), dipyrone (metamizole sodium and metamizole magnesium) (OR, 25.76 [95%
      CI, 8.39-179.12]), and spironolactone (OR, 19.97 [95% CI, 2.27-175.89]). Other
      drugs associated with a significant risk were pyrithyldione, cinepazide,
      aprindine hydrochloride, carbamazepine, sulfonamides, phenytoin and phenytoin
      sodium, beta-lactam antibiotics, erythromycin stearate and erythromycin
      ethylsuccinate, and diclofenac sodium. Individual attributable incidences for all
      these drugs, which collectively accounted for 68.6% of cases, were less than 1:1
      million per year. CONCLUSIONS: Agranulocytosis is rare but serious. A few drugs
      account for two thirds of the cases. Our results also provide reassurance
      regarding the risk associated with a number of newly marketed drugs.

PMID- 15851638
TI  - The metabolic syndrome, cardiopulmonary fitness, and subcutaneous trunk fat as
      independent determinants of arterial stiffness: the Amsterdam Growth and Health
      Longitudinal Study.
AB  - BACKGROUND: The mechanisms that link the metabolic syndrome to increased
      cardiovascular risk are incompletely understood, especially in young people. We
      therefore examined whether the metabolic syndrome was associated with arterial
      stiffness and whether any such associations were independent of cardiopulmonary
      fitness and subcutaneous trunk fat. METHODS: Cross-sectional analyses of data on
      364 men and women aged 36 years from the Amsterdam Growth and Health Longitudinal
      Study (ninth follow-up measurement, year 2000). The prevalence of the metabolic
      syndrome was defined by a slightly modified National Cholesterol Education
      Program (NCEP) definition. Arterial stiffness was ultrasonically estimated by
      distensibility and compliance of the carotid, femoral, and brachial arteries and
      by the carotid elastic modulus. RESULTS: The prevalence of the metabolic syndrome
      in this young adult population was 18.3% in men and 3.2% in women. Individuals
      with the syndrome compared with individuals without risk factors had 11.2% and
      17.0% less distensibility and 9.0% and 18.2% less compliance of the carotid and
      femoral arteries, respectively, and 15.9% higher carotid elastic modulus. After
      adjustment for cardiopulmonary fitness and subcutaneous trunk fat, the metabolic
      syndrome remained significantly associated with stiffness of the carotid but not
      the femoral artery. In addition, poor cardiopulmonary fitness and high
      subcutaneous trunk fat were associated with arterial stiffness, and this was
      independent of the metabolic syndrome. CONCLUSIONS: A modified NCEP definition of
      the metabolic syndrome identified young individuals with increased arterial
      stiffness. The mechanisms that link the metabolic syndrome, poor cardiopulmonary
      fitness, and high subcutaneous trunk fat to greater arterial stiffness overlap
      but are partly independent of each other.

PMID- 15851639
TI  - Risk scores predict atherosclerotic lesions in young people.
AB  - BACKGROUND: Atherosclerosis begins in childhood and progresses through young
      adulthood to form the lesions that cause coronary heart disease. These
      preclinical lesions are associated with coronary heart disease risk factors in
      young persons. METHODS: The Pathobiological Determinants of Atherosclerosis in
      Youth study collected arteries and samples of blood and other tissues from
      persons aged 15 to 34 years who died of external causes and underwent autopsy in
      forensic laboratories. We measured the coronary heart disease risk factors and
      atherosclerotic lesions in the coronary arteries (CAs) (n = 1117) and the
      abdominal aorta (n = 1458). RESULTS: We developed risk scores, normalized so that
      a 1-unit increase was equivalent to a 1-year increase in age, to estimate the
      probability of advanced atherosclerotic lesions in the CAs and the abdominal
      aorta from age, sex, serum lipoprotein concentrations, smoking, hypertension,
      obesity, and hyperglycemia. Odds ratios for a 1-unit increase in the risk scores
      were 1.18 (95% confidence interval, 1.14-1.22) for the CAs and 1.29 (95%
      confidence interval, 1.23-1.35) for the abdominal aorta. These risk scores had
      good discrimination (c-indexes: 0.78 for the CAs and 0.84 for the abdominal
      aorta) and were calibrated. The presence of abdominal aortic lesions increased
      the likelihood of having CA lesions. CONCLUSION: Risk scores calculated from
      traditional coronary heart disease risk factors provide a tool for identifying
      young individuals with a high probability of having advanced atherosclerotic
      lesions.

PMID- 15851640
TI  - Microbiologic determinants of exacerbation in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: The culture of bronchial secretions from the lower airway has been
      reported to be positive for potentially pathogenic microorganisms (PPMs) in
      patients with stable chronic obstructive pulmonary disease (COPD), but the
      determinants and effects of this bacterial load in the airway are not
      established. METHODS: To determine the bronchial microbial pattern in COPD and
      its relationship with exacerbation, we pooled analysis of crude data from studies
      that used protected specimen brush sampling, with age, sex, smoking, lung
      function, and microbiologic features of the lower airway as independent variables
      and exacerbation as the outcome, using logistic regression modeling. RESULTS: Of
      337 study participants, 70 were healthy, 181 had stable COPD, and 86 had
      exacerbated COPD. Differences in the microbial characteristics in the
      participating laboratories were not statistically significant. A cutoff point of
      10(2) colony-forming units (CFU) per milliliter or greater for the identification
      of abnormal positive culture results for PPMs was defined using the 95th
      percentile in the pooled analysis of healthy individuals. Bronchial colonization
      of 10(2) CFU/mL or greater by PPMs was found in 53 patients with stable COPD
      (29%) and in 46 patients with exacerbated COPD (54%) (P<.001, chi(2) test), with
      a predominance of Haemophilus influenzae and Pseudomonas aeruginosa. Higher
      microbial loads were associated with exacerbation and showed a statistically
      significant dose-response relationship after adjustment for covariates (odds
      ratio, 3.62; 95% confidence interval, 1.47-8.90), but P aeruginosa persisted as a
      statistically significant risk factor after adjustment for microbial load (odds
      ratio, 11.12; 95% confidence interval, 1.17-105.82). CONCLUSIONS: One quarter of
      the patients with COPD are colonized by PPMs during their stable periods.
      Exacerbation is associated with the overgrowth of PPMs and with the appearance of
      P aeruginosa in the lower airway, which is associated with exacerbation symptoms
      independent of load.

PMID- 15851641
TI  - Optimizing the prediction of perioperative mortality in vascular surgery by using
      a customized probability model.
AB  - BACKGROUND: Accurately assessing the probability of perioperative mortality can
      be useful in preoperative risk assessment and management. This study aimed to
      revise and customize the revised cardiac risk (Lee) index to estimate the
      probability of perioperative all-cause mortality in patients undergoing
      noncardiac vascular surgery. METHODS: We studied 2310 patients (mean age, 67.8 +/
      11.3 years; 1747 males) who underwent acute or elective major noncardiac
      vascular surgery between January 1, 1991, and December 31, 2000, at the Erasmus
      Medical Center, Rotterdam, the Netherlands. A total of 1537 patients were
      assigned for model development, in which the associations between predictor
      variables and mortality occurring within 30 days after surgery were identified to
      modify the Lee index, which was then evaluated in a validation cohort of 773
      patients. RESULTS: The perioperative mortality rates were similar in the
      development (n = 103 [6.7%]) and validation (n = 50 [6.5%]) populations. The
      customized risk-prediction model for perioperative mortality identified type of
      vascular surgery, ischemic heart disease, congestive heart failure, previous
      stroke, hypertension, renal dysfunction, and chronic pulmonary disease as being
      associated with increased risk, whereas beta-blocker and statin use were
      associated with a lower risk of mortality. The performance of the customized
      index had excellent discriminative ability in both derivation and validation
      populations (concordance statistic, 0.88 and 0.85, respectively). CONCLUSIONS:
      The customized index provides more detailed information than the Lee index about
      the type of vascular procedure, clinical risk factors, and concomitant medication
      use. The customized probability model can be a useful tool to estimate the risk
      of perioperative all-cause mortality and facilitate subsequent treatment
      strategies.

PMID- 15851642
TI  - Incidental vertebral fractures discovered with chest radiography in the emergency
      department: prevalence, recognition, and osteoporosis management in a cohort of
      elderly patients.
AB  - BACKGROUND: Vertebral fractures are common and usually an indication for
      osteoporosis treatment. However, screening is not recommended, and many fractures
      go undetected. Our objectives were to determine the utility of chest radiographs
      for detecting previously unrecognized vertebral fractures; document rates of
      recognition; and evaluate osteoporosis treatments. METHODS: In 2001, we conducted
      a cohort study in a random sample of 500 patients older than 60 years who
      presented to our emergency department and underwent chest radiography for any
      indication. The primary outcome was prevalence of moderate-to-severe vertebral
      fractures determined by independent radiograph review using validated
      semiquantitative techniques. Secondary outcomes were rates of fracture
      recognition according to official radiologists' reports and rates of osteoporosis
      diagnosis and treatment. We conducted multivariable regression analyses to
      determine correlates of study-defined and officially reported fractures. RESULTS:
      We excluded 36 patients with inadequate radiographs and 5 for other reasons. Mean
      age was 75.2 years; 47% were women; and 80% were white. The prevalence of
      moderate-to-severe vertebral fractures according to independent review was 72
      (16%) of 459; 29 (40%) of these fractures were not recorded in the official
      radiologists' report (kappa = 0.64; 95% confidence interval [CI], 0.53-0.75). A
      history of osteoporosis was the only independent correlate of having a vertebral
      fracture identified by independent review (adjusted odds ratio [OR], 2.18; 95%
      CI, 1.14-4.17) or by official report (adjusted OR, 4.97; 95% CI, 0.95-25.86). Of
      the 72 patients with fractures, only 18 (25%) had histories of osteoporosis or
      received osteoporosis medications. CONCLUSIONS: One in 6 elderly patients who
      underwent chest radiography in our emergency department had clinically important
      vertebral fractures. Nevertheless, only 43 (60%) of these fractures were
      reported, and only 25% of patients with fractures received a diagnosis of or
      treatment for osteoporosis.

PMID- 15851643
TI  - The association of obesity, cytokine levels, and depressive symptoms with diverse
      measures of fatigue in healthy subjects.
AB  - BACKGROUND: Fatigue is a common symptom, even among healthy individuals, but
      little is understood about it. We examined the associations among adiposity,
      depressive symptoms, cytokine levels, and multidimensional fatigue symptoms in
      otherwise healthy subjects. Furthermore, we examined whether obesity would
      account for a significant portion of fatigue and, if so, what kind of fatigue
      complaints appear to be related to obesity. METHODS: Seventy healthy subjects (36
      women and 34 men) with an average age of 36.0 years and at less than or equal to
      170% of ideal body weight participated in the study. Participants had their
      height, weight, neck circumference, ratio of the waist to hip circumference,
      percentage of body fat, and plasma interleukin 6 and soluble intercellular
      adhesion molecule 1 concentrations measured. Their sleep was monitored with an
      overnight polysomnogram, and subjects completed the short form of the
      Multidimensional Fatigue Symptom Inventory, which measures 5 domains of fatigue,
      and the Center for Epidemiologic Studies-Depression Scale. RESULTS: Obesity, as
      measured by body mass index (calculated as weight in kilograms divided by the
      square of height in meters) and percentage of body fat, was associated with
      general fatigue. Depression scores were significantly related to all subscales of
      fatigue; the highest correlation was shown with emotional fatigue. The effect of
      obesity on physical fatigue was significant, even after controlling for
      depression. In general, interleukin 6 and soluble intercellular adhesion molecule
      1 levels were unrelated to measures of fatigue. CONCLUSIONS: Obesity, cytokine
      concentrations, and depressive symptoms explained different dimensions of fatigue
      as measured by the short form of the Multidimensional Fatigue Symptom Inventory.
      Obesity accounted for a significant portion of physical fatigue after controlling
      for depressive symptoms and circulating levels of interleukin 6 and soluble
      intercellular adhesion molecule-1.

PMID- 15851644
TI  - Does hypertension protect against chronic musculoskeletal complaints? The Nord
      Trondelag Health Study.
AB  - BACKGROUND: Although an inverse relationship between pain sensitivity and
      hypertension has been described, it is still unknown whether hypertension may
      protect against chronic musculoskeletal complaints (MSCs). The aim of this study
      was to evaluate the relationship between blood pressure (BP) and prevalence of
      chronic MSCs at various anatomical sites. METHODS: Two consecutive public health
      studies within the county of Nord-Trondelag, Norway, were conducted between
      January 5, 1984, and February 15, 1986 (Nord-Trondelag Health Study [HUNT] 1),
      and from August 1995 to June 1997 (HUNT-2). Among 46 901 adults who participated
      in both surveys, 24 127 (51.4%) in HUNT-2 who reported MSCs continuously for at
      least 3 months during the past year were defined as having chronic MSCs. The
      prevalence of chronic MSCs was estimated using multiple logistic regression, with
      odds ratio and 95% confidence interval as measures of association with systolic
      and diastolic BP. RESULTS: A high systolic and diastolic BP was associated with a
      10% to 60% lower prevalence of chronic MSCs, and there was a strong linear trend
      (P<.001) of decreasing prevalence of chronic MSCs with increasing BP values. The
      findings were remarkably consistent at all anatomical sites, for both sexes,
      across all age groups, and for systolic and diastolic BP measured in HUNT-1 and
      HUNT-2. CONCLUSIONS: Individuals with a high BP had a lower prevalence of chronic
      MSCs than individuals with a normal BP. One possible explanation may be the
      phenomenon of hypertension-associated hypalgesia, due to an interaction between
      the cardiovascular and pain regulatory systems. The effect of antihypertensive
      medication on this interaction should be evaluated in further studies.

PMID- 15851645
TI  - Elevated blood pressure and risk of end-stage renal disease in subjects without
      baseline kidney disease.
AB  - BACKGROUND: Many cases of end-stage renal disease (ESRD) are ascribed to
      hypertension. However, because renal disease itself can raise blood pressure,
      some investigators argue that ESRD seen in patients with hypertension is due to
      underlying primary renal disease. Previous cohort studies of the relationship
      between blood pressure and ESRD did not uniformly screen out baseline kidney
      disease. METHODS: We conducted a historical cohort study among members of Kaiser
      Permanente of Northern California, a large integrated health care delivery
      system. The ESRD cases were ascertained by matching with the US Renal Data System
      registry. RESULTS: A total of 316 675 adult Kaiser members participated in the
      Multiphasic Health Checkups from 1964 to 1985. All subjects had estimated
      glomerular filtration rates of 60 mL /min per 1.73 m(2) or higher and negative
      dipstick urinalysis results for proteinuria or hematuria. During 8 210 431 person
      years of follow-up, 1149 cases of ESRD occurred. Compared with subjects with a
      blood pressure less than 120/80 mm Hg, the adjusted relative risks for developing
      ESRD were 1.62 (95% confidence interval [CI], 1.27-2.07) for blood pressures of
      120 to 129/80 to 84 mm Hg, 1.98 (95% CI, 1.55-2.52) for blood pressures of 130 to
      139/85 to 89 mm Hg, 2.59 (95% CI, 2.07-3.25) for blood pressures of 140 to 159/90
      to 99 mm Hg, 3.86 (95% CI, 3.00-4.96) for blood pressures of 160 to 179/100 to
      109 mm Hg, 3.88 (95% CI, 2.82-5.34) for blood pressures of 180 to 209/110 to 119
      mm Hg, and 4.25 (95% CI, 2.63-6.86) for blood pressures of 210/120 mm Hg or
      higher. Similar associations between blood pressure level and ESRD risk were seen
      in all subgroup analyses. CONCLUSIONS: Even relatively modest elevation in blood
      pressure is an independent risk factor for ESRD. The observed relationship does
      not appear to be due to confounding by clinically evident baseline kidney
      disease.

PMID- 15851646
TI  - Mediterranean diet and survival among patients with coronary heart disease in
      Greece.
AB  - BACKGROUND: The Mediterranean diet has been hypothesized to reduce fatality among
      patients with coronary heart disease. METHODS: We examined the association
      between the degree of adherence to the traditional Mediterranean diet and
      survival of persons with diagnosed coronary heart disease at enrollment, in a
      population-based prospective investigation of 1302 Greek men and women, who were
      followed up for an average of 3.78 years (the European Prospective Investigation
      Into Cancer and Nutrition cohort). Information on usual dietary intakes during
      the year preceding enrollment was recorded through a validated food frequency
      questionnaire. Adherence to the Mediterranean diet was assessed by a 10-unit
      Mediterranean diet score that incorporates the salient characteristics of this
      diet. Proportional hazards regression was used to assess the relation of overall
      degree of adherence to the Mediterranean diet with mortality overall or by cause
      (cardiac vs noncardiac). RESULTS: Higher adherence to the Mediterranean diet by 2
      units was associated with a 27% lower mortality rate among persons with prevalent
      coronary heart disease at enrollment (total deaths, 131; adjusted mortality
      ratio, 0.73; 95% confidence interval, 0.58-0.93). The reduced mortality was more
      evident and amounted to 31% (total deaths, 85; adjusted mortality ratio, 0.69;
      95% confidence interval, 0.52-0.93) when only cardiac deaths were considered as
      the relevant outcome. Associations between individual food groups contributing to
      the Mediterranean diet score and mortality were generally not significant.
      CONCLUSION: Greater adherence to the traditional Mediterranean diet is associated
      with a significant reduction in mortality among individuals diagnosed as having
      coronary heart disease.

PMID- 15851647
TI  - Renal outcomes in high-risk hypertensive patients treated with an angiotensin
      converting enzyme inhibitor or a calcium channel blocker vs a diuretic: a report
      from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
      Trial (ALLHAT).
AB  - BACKGROUND: This study was performed to determine whether, in high-risk
      hypertensive patients with a reduced glomerular filtration rate (GFR), treatment
      with a calcium channel blocker or an angiotensin-converting enzyme inhibitor
      lowers the incidence of renal disease outcomes compared with treatment with a
      diuretic. METHODS: We conducted post hoc analyses of the Antihypertensive and
      Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertensive
      participants 55 years or older with at least 1 other coronary heart disease risk
      factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a
      mean of 4.9 years. Renal outcomes were incidence of end-stage renal disease
      (ESRD) and/or a decrement in GFR of 50% or more from baseline. Baseline GFR,
      estimated by the simplified Modification of Diet in Renal Disease equation, was
      stratified into normal or increased (> or =90 mL /min per 1.73 m(2), n = 8126),
      mild reduction (60-89 mL /min per 1.73 m(2), n = 18 109), or moderate-severe
      reduction (<60 mL /min per 1.73 m(2), n = 5662) in GFR. Each stratum was analyzed
      for effects of the treatments on outcomes. RESULTS: In 448 participants, ESRD
      developed. Compared with patients taking chlorthalidone, no significant
      differences occurred in the incidence of ESRD in patients taking amlodipine in
      the mild (relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) or
      moderate-severe (RR, 0.92; 95% CI, 0.68-1.24) reduction in GFR groups. Compared
      with patients taking chlorthalidone, no significant differences occurred in the
      incidence of ESRD in patients taking lisinopril in the mild (RR, 1.34; 95% CI,
      0.87-2.06) or moderate-severe (RR, 0.98; 95% CI, 0.73-1.31) reduction in GFR
      groups. In patients with mild and moderate-severe reduction in GFR, the incidence
      of ESRD or 50% or greater decrement in GFR was not significantly different in
      patients treated with chlorthalidone compared with those treated with amlodipine
      (odds ratios, 0.96 [P = .74] and 0.85 [P = .23], respectively) and lisinopril
      (odds ratios, 1.13 [P = .31] and 1.00 [P = .98], respectively). No difference in
      treatment effects occurred for either end point for patients taking amlodipine or
      lisinopril compared with those taking chlorthalidone across the 3 GFR subgroups,
      either for the total group or for participants with diabetes at baseline. At 4
      years of follow-up, estimated GFR was 3 to 6 mL /min per 1.73 m(2) higher in
      patients assigned to receive amlodipine compared with chlorthalidone, depending
      on baseline GFR stratum. CONCLUSIONS: In hypertensive patients with reduced GFR,
      neither amlodipine nor lisinopril was superior to chlorthalidone in reducing the
      rate of development of ESRD or a 50% or greater decrement in GFR. Participants
      assigned to receive amlodipine had a higher GFR than those assigned to receive
      chlorthalidone, but rates of development of ESRD were not different between the
      groups.

PMID- 15851648
TI  - The relationship between magnitude of proteinuria reduction and risk of end-stage
      renal disease: results of the African American study of kidney disease and
      hypertension.
AB  - BACKGROUND: The magnitude of proteinuria is associated with a graded increase in
      the risk of progression to end-stage renal disease and cardiovascular events. The
      objective of this study was to relate baseline and early changes in proteinuria
      and glomerular filtration rate (GFR) to long-term progression of hypertensive
      nondiabetic kidney disease. METHODS: Post hoc analysis of a randomized 3 x 2
      factorial trial. A total of 1094 African Americans with hypertensive renal
      disease (GFR, 20-65 mL/min per 1.73 m(2)) were followed up for a median of 3.8
      years. Participants were randomized to a mean arterial pressure goal of 102 to
      107 mm Hg (usual) or 92 mm Hg or less (lower) and to initial treatment with a
      beta-blocker (metoprolol), an angiotensin-converting enzyme inhibitor (ramipril),
      or a dihydropyridine calcium channel blocker (amlodipine) RESULTS: Baseline
      proteinuria and GFR predicted the rgate of GFR decline. For each 10-mL/min per
      1.73 m(2) lower baseline GFR, an associated mean +/- SE 0.38 +/- 0.08-mL/min per
      1.73 m(2) per year greater mean GFR decline occurred, and for each 2-fold higher
      proteinuria level, a mean +/- SE 0.54 +/- 0.05-mL/min per 1.73 m(2) per year
      faster GFR decline was observed (P < .001 for both). In multivariate analysis,
      the effect of baseline proteinuria GFR decline persisted. Initial change in
      proteinuria from baseline to 6 months predicted subsequent progression, with this
      relationship extending to participants with baseline urinary protein levels less
      than 300 mg/d. CONCLUSIONS: The change in the level of proteinuria is a predictor
      of subsequent progression of hypertensive kidney disease at a given GFR. A
      prospective trial is needed to confirm this observation.

PMID- 15851649
TI  - The demise of the sinus headache is premature.

PMID- 15851651
TI  - Suramin and disulfonated stilbene derivatives stimulate the Ca2+-induced Ca2+ 
      release mechanism in A7r5 cells.
AB  - We have described previously a novel Ca2+-induced Ca2+-release (CICR) mechanism
      in permeabilized A7r5 cells (embryonic rat aorta) and 16HBE14o-cells (human
      bronchial mucosa) cells (J Biol Chem 278:27548-27555, 2003). This CICR mechanism
      was activated upon the elevation of the free cytosolic calcium concentration
      [Ca2+]c and was not inhibited by pharmacological inhibitors of the inositol-1,4,5
      trisphosphate (IP3) receptor nor of the ryanodine receptor. This CICR mechanism
      was inhibited by calmodulin (CaM)1234, a Ca2+-insensitive CaM mutant, and by
      different members of the superfamily of CaM-like Ca2+-binding proteins. Here, we
      present evidence that the CICR mechanism that is expressed in A7r5 and 16HBE14o
      cells is strongly activated by suramin and 4,4'-diisothiocyanatostilbene-2,2'
      disulfonic acid (DIDS). We found several indications that both activation
      mechanisms are indeed two different modes of the same release system.
      Suramin/DIDS-induced Ca2+ release was only detected in cells that displayed the
      CICR mechanism, and cell types that do not express this type of CICR mechanism
      did not exhibit suramin/DIDS-induced Ca2+ release. Furthermore, we show that the
      suramin-stimulated Ca2+ release is regulated by Ca2+ and CaM in a similar way as
      the previously described CICR mechanism. The pharmacological characterization of
      the suramin/DIDS-induced Ca2+ release further confirms its properties as a novel
      CaM-regulated Ca2+-release mechanism. We also investigated the effects of
      disulfonated stilbene derivatives on IP3-induced Ca2+ release and found, in
      contrast to the effect on CICR, a strong inhibition by DIDS and 4'-acetoamido-4'
      isothiocyanostilbene-2',2'-disulfonic acid.

PMID- 15851652
TI  - Intragenic suppression of trafficking-defective KCNH2 channels associated with
      long QT syndrome.
AB  - Mutations in the KCNH2 or human ether-a-go-go-related gene-encoded K(+) channel
      reduce functional KCNH2 current (I(KCNH2)) to cause long QT syndrome (LQT2) by
      multiple mechanisms, including defects in intracellular transport (trafficking).
      Trafficking-deficient, or class 2, LQT2 mutations reduce the Golgi processing and
      surface membrane expression of KCNH2 channel proteins. Drugs that associate with
      pore-S6 intracellular drug binding domain of KCNH2 channel proteins to cause high
      affinity block of I(KCNH2) also can increase the processing of class 2 LQT2
      channel proteins through the secretory pathway. We used a strategy of intragenic
      suppression to test the hypothesis that amino acid substitutions in the putative
      drug binding domain at residue Y652 could compensate for protein folding
      abnormalities caused by class 2 LQT2 mutations. We found that the Y652C
      substitution, and to lesser extent the Y652S substitution, resulted in intragenic
      suppression of the class 2 LQT2 G601S phenotype; these substitutions increased
      Golgi processing of G601S channel proteins. The Y652C substitution also caused
      intragenic suppression of the class 2 LQT2 V612L and F640V phenotypes but not the
      LQT2 N470D or F805C phenotypes. These are the first findings to demonstrate that
      a single amino acid substitution in the putative KCNH2 drug binding domain can
      cause intragenic suppression of several LQT2 mutations.

PMID- 15851653
TI  - Erection capability is potentiated by long-term sildenafil treatment: role of
      blood flow-induced endothelial nitric-oxide synthase phosphorylation.
AB  - Despite demonstrated clinical efficacy of sildenafil for the temporary treatment
      of erectile dysfunction, the possibility that sildenafil used long-term durably
      augments erectile ability remains unclear. We investigated whether continuous
      long-term administration of sildenafil at clinically relevant levels to aged rats
      "primes" the penis for improved erectile ability and involves nitric oxide (NO)
      or RhoA/Rho-kinase signaling pathways. In aged, but not young rats, sildenafil
      prolonged erection and increased the protein expressions of phosphorylated
      endothelial NO synthase (eNOS) at serine-1177 and phosphorylated Akt at serine
      473 in penes. Only in the young rat penis, protein expressions of
      phosphodiesterase-5 and phosphomyosin phosphatase target subunit 1, a marker of
      Rho-kinase activity, were increased by sildenafil. Sildenafil inhibited
      phosphodiesterase-5 activity in penes of young and aged rats coincident with
      assayed free plasma levels of the drug equivalent to clinically therapeutic
      measurements. We conclude that erectile ability can be enhanced under
      preconditions of erectile impairment by long-term inhibition of phosphodiesterase
      5 and that the effect is mediated by Akt-dependent eNOS phosphorylation. The lack
      of erectile ability enhancement in young rats by long-term phosphodiesterase-5
      inhibition may relate to restrained NO signaling by phosphodiesterase-5 up
      regulation, lack of incremental Akt and eNOS phosphorylation, and heightened Rho
      kinase signaling in the penis.

PMID- 15851654
TI  - Inhibition of T-type calcium channels protects neurons from delayed ischemia
      induced damage.
AB  - Intracellular calcium increase is an early key event triggering ischemic neuronal
      cell damage. The role of T-type voltage-gated calcium channels in the neuronal
      response to ischemia, however, has never been studied. Using an in vitro model of
      ischemia-induced delayed cell death in rat organotypic hippocampal slice
      cultures, we show that T-type calcium channels inhibitors drastically reduce
      ischemic cell damage. Immunostaining studies reveal the existence of Ca(V)3.1 and
      Ca(V)3.2 types of low-voltage-activated calcium channels in rat organotypic
      hippocampal cultures. Low extracellular calcium (100 nM) or increase of
      intracellular calcium buffering ability by BAPTA-acetoxymethyl ester
      significantly reduced ischemia-induced neuronal damage. Pharmacological
      inhibition of the T-type calcium current by mibefradil, kurtoxin, nickel, zinc,
      and pimozide during the oxygen-glucose deprivation episode provided a significant
      protection against delayed neuronal death. Mibefradil and nickel exerted
      neuroprotective effects, not only if administrated during the oxygen-glucose
      deprivation episode but also in conditions of postischemic treatment. These data
      point to a role of T-type calcium currents in ischemia-induced, calcium-mediated
      neuronal cell damage and suggest a possible new pharmacological approach to
      stroke treatment.

PMID- 15851655
TI  - Recruiting dendritic cells to improve antibody therapy of cancer.

PMID- 15851656
TI  - Distinct role of lymphocyte function-associated antigen-1 in mediating effective
      cytolytic activity by cytotoxic T lymphocytes.
AB  - Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular
      adhesion molecules (ICAMs) facilitates T cell antigen receptor (TCR)-mediated
      killing. To dissect TCR and LFA-1 contributions, we evaluated cytolytic activity
      and granule release by cytotoxic T lymphocytes (CTL) as well as intracellular
      granule redistribution and morphology of CTL stimulated with natural TCR ligand
      in the presence or absence of LFA-1 engagement. Although other adhesion
      mechanisms, e.g., CD2-CD58 interaction, could substitute for LFA-1 to trigger CTL
      degranulation, productive LFA-1 ligation was indispensable for effective target
      cell lysis by the released granules. LFA-1-mediated adhesion to glass-supported
      bilayers containing intercellular adhesion molecule-1 was characterized by a much
      larger junction area, marked by LFA-1 segregation, and a more compact cell shape
      compared with those observed for CD2-mediated adhesion to bilayers containing
      CD58. A larger contact induced by intercellular adhesion molecule 1 determined a
      unique positioning of granules near the interface. These data provide evidence
      that LFA-1 delivers a distinct signal essential for directing released cytolytic
      granules to the surface of antigen-bearing target cells to mediate the effective
      destruction of these cells by CTL.

PMID- 15851657
TI  - Mutagenesis by reversible promoter insertion to study the activation of NF
      kappaB.
AB  - Genetic dissection of signaling pathways in mammalian cells involves screening or
      selecting phenotypic mutants obtained by a variety of techniques. Limitations in
      current methods include inadequate genome coverage and difficulty in validating
      the link between mutation and phenotype. We describe an improved method for
      insertional mutagenesis with retroviral vectors and show that the ability to
      induce mutations increases greatly if a randomly inserted promoter directs
      transcription into the host DNA. The mutant phenotype is due to the expression of
      a hybrid transcript derived from the vector and the insertion site. Because other
      alleles of the affected gene remain intact, the phenotype is dominant, but is
      reversible by inactivating the promoter, for example, by site-specific
      recombination. Importantly, in mutant clones with multiple inserts, limited
      excision yields progeny with different patterns of inserts remaining.
      Characterizing these progeny allows the mutant phenotype to be associated with a
      specific target gene. Relative simplicity and robust target validation make the
      method suitable for a broad range of applications. We have used this technique to
      search for proteins that regulate NF-kappaB-dependent signaling in human cells.
      Two validated targets are the relA gene, which codes for the NF-kappaB p65
      subunit, and the NF-kappaB regulator act1. Overexpression of the corresponding
      proteins, caused by insertion of a promoter into the first intron of each gene,
      leads to NF-kappaB-dependent secretion of factors that activate NF-kappaB through
      cell-surface receptors, establishing an autocrine loop.

PMID- 15851658
TI  - Evolutionary origin of cAMP-based chemoattraction in the social amoebae.
AB  - Phenotypic novelties can arise if integrated developmental pathways are expressed
      at new developmental stages and then recruited to serve new functions. We analyze
      the origin of a novel developmental trait of Dictyostelid amoebae: the evolution
      of cAMP as a developmental chemoattractant. We show that cAMP's role of
      attracting starving amoebae arose through recruitment of a pathway that
      originally evolved to coordinate fruiting body morphogenesis. Orthologues of the
      high-affinity cAMP receptor (cAR), cAR1, were identified in a selection of
      species that span the Dictyostelid phylogeny. The cAR1 orthologue from the basal
      species Dictyostelium minutum restored aggregation and development when expressed
      in an aggregation-defective mutant of the derived species Dictyostelium
      discoideum that lacks high-affinity cARs, thus demonstrating that the D. minutum
      cAR is a fully functional cAR. cAR1 orthologues from basal species are expressed
      during fruiting body formation, and only this process, and not aggregation, was
      disrupted by abrogation of cAR1 function. This is in contrast to derived species,
      where cAR1 is also expressed during aggregation and critically regulates this
      process. Our data show that coordination of fruiting body formation is the
      ancestral function of extracellular cAMP signaling, whereas its derived role in
      aggregation evolved by recruitment of a preexisting pathway to an earlier stage
      of development. This most likely occurred by addition of distal cis-regulatory
      regions to existing cAMP signaling genes.

PMID- 15851660
TI  - Systematics and the origin of species: an introduction.

PMID- 15851659
TI  - Genetics and genomics of Drosophila mating behavior.
AB  - The first steps of animal speciation are thought to be the development of sexual
      isolating mechanisms. In contrast to recent progress in understanding the genetic
      basis of postzygotic isolating mechanisms, little is known about the genetic
      architecture of sexual isolation. Here, we have subjected Drosophila melanogaster
      to 29 generations of replicated divergent artificial selection for mating speed.
      The phenotypic response to selection was highly asymmetrical in the direction of
      reduced mating speed, with estimates of realized heritability averaging 7%. The
      selection response was largely attributable to a reduction in female receptivity.
      We assessed the whole genome transcriptional response to selection for mating
      speed using Affymetrix GeneChips and a rigorous statistical analysis. Remarkably,
      >3,700 probe sets (21% of the array elements) exhibited a divergence in message
      levels between the Fast and Slow replicate lines. Genes with altered
      transcriptional abundance in response to selection fell into many different
      biological process and molecular function Gene Ontology categories, indicating
      substantial pleiotropy for this complex behavior. Future functional studies are
      necessary to test the extent to which transcript profiling of divergent selection
      lines accurately predicts genes that directly affect the selected trait.

PMID- 15851661
TI  - Systematics and the future of biology.

PMID- 15851662
TI  - Differences in color vision make passerines less conspicuous in the eyes of their
      predators.
AB  - Sexual selection often favors brighter and exaggerated traits, which also
      increase the risk of detection by predators. Signals that are preferentially
      conspicuous to conspecifics would reduce the predation cost of signaling and,
      therefore, might facilitate the evolution of stronger sexual and social signals.
      This selective signaling is possible if predators and prey have differently tuned
      sensory systems. By using a retinal model to compare reflectance from the
      plumages of Swedish songbirds to the reflectance of their natural backgrounds, we
      found their color badges to be significantly more conspicuous to other songbirds
      (which have a UV-tuned visual system) than to raptors and corvids (which have a
      violet-tuned system) in both coniferous and deciduous forests, consistent with an
      adaptive private communication system.

PMID- 15851663
TI  - Evaluating putative mechanisms of the mitotic spindle checkpoint.
AB  - The mitotic spindle checkpoint halts the cell cycle until all chromosomes are
      attached to the mitotic spindles. Evidence suggests that the checkpoint prevents
      cell-cycle progression by inhibiting the activity of the APC-Cdc20 complex, but
      the precise mechanism underlying this inhibition is not yet known. Here, we use
      mathematical modeling to compare several mechanisms that could account for this
      inhibition. We describe the interplay between the capacities to strongly inhibit
      cell-cycle progression before spindle attachment on one hand and to rapidly
      resume cell-cycle progression once the last kinetochore is attached on the other
      hand. We find that inhibition that is restricted to the kinetochore region is not
      sufficient for supporting both requirements when realistic diffusion constants
      are considered. A mechanism that amplifies the checkpoint signal through
      autocatalyzed inhibition is also insufficient. In contrast, amplifying the signal
      through the release of a diffusible inhibitory complex can support reliable
      checkpoint function. Our results suggest that the design of the spindle
      checkpoint network is limited by physical constraints imposed by realistic
      diffusion constants and the relevant spatial and temporal dimensions where
      computation is performed.

PMID- 15851664
TI  - Transgenic engineering of male-specific muscular hypertrophy.
AB  - Using a two-step procedure involving insertional gene targeting and recombinase
      mediated cassette exchange in ES cells, we have produced two lines of transgenic
      mice expressing a dominant-negative latency-associated myostatin propeptide under
      control of the myosin light chain 1F promoter and 1/3 enhancer from the TSPY
      locus on the Y chromosome. Males of the corresponding lines are characterized by
      a 5-20% increase in skeletal muscle mass. This experiment demonstrates the
      feasibility of a more efficient cattle production system combining superior beef
      production abilities for bulls and dairy abilities for cows.

PMID- 15851665
TI  - On the origin of Lake Malawi cichlid species: a population genetic analysis of
      divergence.
AB  - The cichlid fishes of Lake Malawi are famously diverse. However, phylogenetic and
      population genetic studies of their history have been difficult because of the
      great amount of genetic variation that is shared between species. We apply a
      recently developed method for fitting the "isolation with migration" divergence
      model to a data set of specially designed compound loci to develop portraits of
      cichlid species divergence. Outgroup sequences from a cichlid from Lake
      Tanganyika permit model parameter estimates in units of years and effective
      population sizes. Estimated speciation times range from 1,000 to 17,000 years for
      species in the genus Tropheops. These exceptionally recent dates suggest that
      Malawi cichlids as a group experience a very active and dynamic diversification
      process. Current effective population size estimates range form 2,000 to near
      40,000, and to >120,000 for estimates of ancestral population sizes. It appears
      that very recent speciation and gene flow are among the reasons why it has been
      difficult to discern the phylogenetic history of Malawi cichlids.

PMID- 15851666
TI  - A multidimensional approach for detecting species patterns in Malagasy
      vertebrates.
AB  - The biodiversity of Madagascar is extraordinarily distinctive, diverse, and
      endangered. It is therefore urgent that steps be taken to document, describe,
      interpret, and protect this exceptional biota. As a collaborative group of field
      and laboratory biologists, we employ a suite of methodological and analytical
      tools to investigate the vertebrate portion of Madagascar's fauna. Given that
      species are the fundamental unit of evolution, where micro- and macroevolutionary
      forces converge to generate biological diversity, a thorough understanding of
      species distribution and abundance is critical for understanding the
      evolutionary, ecological, and biogeographic forces that have shaped Malagasy
      vertebrate diversity. We illustrate the means by which we apply Mayr's "three
      basic tasks" of the systematist [Mayr, E. (1942) Systematics and the Origin of
      Species from the Viewpoint of a Zoologist (Harvard Univ. Press, Cambridge, MA)]
      to identify, classify, and study the organisms that together constitute
      Madagascar's vertebrate community. Using field inventory methods, specimen-based
      studies, and morphological and molecular analyses, we formulate hypotheses of
      species identity that then serve as the foundation for subsequent studies of
      biology and history. Our experience, as well as that of other investigators, has
      shown that much of the vertebrate species diversity in Madagascar is "cryptic"
      for both biological and practical reasons. Beyond issues of cryptic biological
      diversity, the resolution of species identity in Madagascar has been hampered
      because of a lack of vouchered comparative material at the population level.
      Through our activities, we are attempting to remedy these limitations while
      simultaneously enhancing research capacity in Madagascar.

PMID- 15851667
TI  - Decoding the genomic tree of life.
AB  - Genomes hold within them the record of the evolution of life on Earth. But genome
      fusions and horizontal gene transfer (HGT) seem to have obscured sufficiently the
      gene sequence record such that it is difficult to reconstruct the phylogenetic
      tree of life. HGT among prokaryotes is not random, however. Some genes
      (informational genes) are more difficult to transfer than others (operational
      genes). Furthermore, environmental, metabolic, and genetic differences among
      organisms restrict HGT, so that prokaryotes preferentially share genes with other
      prokaryotes having properties in common, including genome size, genome G+C
      composition, carbon utilization, oxygen utilization/sensitivity, and temperature
      optima, further complicating attempts to reconstruct the tree of life. A new
      method of phylogenetic reconstruction based on gene presence and absence, called
      conditioned reconstruction, has improved our prospects for reconstructing
      prokaryotic evolution. It is also able to detect past genome fusions, such as the
      fusion that appears to have created the first eukaryote. This genome fusion
      between a deep branching eubacterium, possibly an ancestor of the cyanobacterium
      and a proteobacterium, with an archaeal eocyte (crenarchaea), appears to be the
      result of an early symbiosis. Given new tools and new genes from relevant
      organisms, it should soon be possible to test current and future fusion theories
      for the origin of eukaryotes and to discover the general outlines of the
      prokaryotic tree of life.

PMID- 15851668
TI  - Genomes, phylogeny, and evolutionary systems biology.
AB  - With the completion of the human genome and the growing number of diverse genomes
      being sequenced, a new age of evolutionary research is currently taking shape.
      The myriad of technological breakthroughs in biology that are leading to the
      unification of broad scientific fields such as molecular biology, biochemistry,
      physics, mathematics, and computer science are now known as systems biology.
      Here, I present an overview, with an emphasis on eukaryotes, of how the
      postgenomics era is adopting comparative approaches that go beyond comparisons
      among model organisms to shape the nascent field of evolutionary systems biology.

PMID- 15851669
TI  - Inter-locus antagonistic coevolution as an engine of speciation: assessment with
      hemiclonal analysis.
AB  - One of Ernst Mayr's legacies is the consensus that the allopatry model is the
      predominant mode of speciation in most sexually reproducing lineages. In this
      model, reproductive isolation develops as a pleiotropic byproduct of the genetic
      divergence that develops among physically isolated populations. Presently, there
      is no consensus concerning which, if any, evolutionary process is primarily
      responsible for driving the specific genetic divergence that leads to
      reproductive isolation. Here, we focus on the hypothesis that inter-locus
      antagonistic coevolution drives rapid genetic divergence among allopatric
      populations and thereby acts as an important "engine" of speciation. We assert
      that only data from studies of experimental evolution, rather than descriptive
      patterns of molecular evolution, can provide definitive evidence for this
      hypothesis. We describe and use an experimental approach, called hemiclonal
      analysis, that can be used in the Drosophila melanogaster laboratory model system
      to simultaneously screen nearly the entire genome for both standing genetic
      variation within a population and the net-selection gradient acting on the
      variation. Hemiclonal analysis has four stages: (i) creation of a laboratory
      "island population"; (ii) cytogenetic cloning of nearly genome-wide haplotypes to
      construct hemiclones; (iii) measurement of additive genetic variation among
      hemiclones; and (iv) measurement of the selection gradient acting on phenotypic
      variation among hemiclones. We apply hemiclonal analysis to test the hypothesis
      that there is ongoing antagonistic coevolution between the sexes in the D.
      melanogaster laboratory model system and then discuss the relevance of this
      analysis to natural systems.

PMID- 15851670
TI  - Varicella-zoster virus infection of human dorsal root ganglia in vivo.
AB  - Varicella-zoster virus (VZV) causes varicella and establishes latency in sensory
      ganglia. VZV reactivation results in herpes zoster. We developed a model using
      human dorsal root ganglion (DRG) xenografts in severe combined immunodeficient
      (SCID) mice to investigate VZV infection of differentiated neurons and satellite
      cells in vivo. DRG engrafted under the kidney capsule and contained neurons and
      satellite cells within a typical DRG architecture. VZV clinical isolates infected
      the neurons within DRG. At 14 days postinfection, VZ virions were detected by
      electron microscopy in neuronal cell nuclei and cytoplasm but not in satellite
      cells. The VZV genome copy number was 7.1 x 10(7) to 8.0 x 10(8) copies per 10(5)
      cells, and infectious virus was recovered. This initial phase of viral
      replication was followed within 4-8 weeks by a transition to VZV latency,
      characterized by the absence of infectious virus release, the cessation of virion
      assembly, and a reduction in VZV genome copies to 3.7 x 10(5) to 4.7 x 10(6) per
      10(5) cells. VZV persistence in DRG was achieved without any requirement for VZV
      specific adaptive immunity and was associated with continued transcription of the
      ORF63 regulatory gene. The live attenuated varicella vaccine virus exhibited the
      same pattern of short-term replication, persistence of viral DNA, and prominent
      ORF63 transcription as the clinical isolates. VZV-infected T cells transferred
      virus from the circulation into DRG, suggesting that VZV lymphotropism
      facilitates its neurotropism. DRG xenografts may be useful for investigating
      neuropathogenic mechanisms of other human viruses.

PMID- 15851671
TI  - Rapid electrostatic evolution at the binding site for cytochrome c on cytochrome
      c oxidase in anthropoid primates.
AB  - Cytochrome c (CYC) oxidase (COX), a multisubunit enzyme that functions in
      mitochondrial aerobic energy production, catalyzes the transfer of electrons from
      CYC to oxygen and participates in creating the electrochemical gradient used for
      ATP synthesis. Modeling three-dimensional structural data on COX and CYC reveals
      that 57 of the >1,500 COX residues can be implicated in binding CYC. Because of
      the functional importance of the transfer of electrons to oxygen, it might be
      expected that natural selection would drastically constrain amino acid
      replacement rates of CYC and COX. Instead, in anthropoid primates, although not
      in other mammals, CYC and COX show markedly accelerated amino acid replacement
      rates, with the COX acceleration being much greater at the positions that bind
      CYC than at those that do not. Specifically, in the anthropoid lineage descending
      from the last common ancestor of haplorhines (tarsiers and anthropoids) to that
      of anthropoids (New World monkeys and catarrhines) and that of catarrhines (Old
      World monkeys and apes, including humans), a minimum of 27 of the 57 COX amino
      acid residues that bind CYC were replaced, most frequently from electrostatically
      charged to noncharged residues. Of the COX charge-bearing residues involved in
      binding CYC, half (11 of 22) have been replaced with uncharged residues. CYC
      residues that interact with COX residues also frequently changed, but only two of
      the CYC changes altered charge. We suggest that reducing the electrostatic
      interaction between COX and CYC was part of the adaptive evolution underlying the
      emergence of anthropoid primates.

PMID- 15851673
TI  - Examining bacterial species under the specter of gene transfer and exchange.
AB  - Even in lieu of a dependable species concept for asexual organisms, the
      classification of bacteria into discrete taxonomic units is considered to be
      obstructed by the potential for lateral gene transfer (LGT) among lineages at
      virtually all phylogenetic levels. In most bacterial genomes, large proportions
      of genes are introduced by LGT, as indicated by their compositional features
      and/or phylogenetic distributions, and there is also clear evidence of LGT
      between very distantly related organisms. By adopting a whole-genome approach,
      which examined the history of every gene in numerous bacterial genomes, we show
      that LGT does not hamper phylogenetic reconstruction at many of the shallower
      taxonomic levels. Despite the high levels of gene acquisition, the only taxonomic
      group for which appreciable amounts of homologous recombination were detected was
      within bacterial species. Taken as a whole, the results derived from the analysis
      of complete gene inventories support several of the current means to recognize
      and define bacterial species.

PMID- 15851674
TI  - Ernst Mayr and the modern concept of species.
AB  - Ernst Mayr played a central role in the establishment of the general concept of
      species as metapopulation lineages, and he is the author of one of the most
      popular of the numerous alternative definitions of the species category.
      Reconciliation of incompatible species definitions and the development of a
      unified species concept require rejecting the interpretation of various
      contingent properties of metapopulation lineages, including intrinsic
      reproductive isolation in Mayr's definition, as necessary properties of species.
      On the other hand, the general concept of species as metapopulation lineages
      advocated by Mayr forms the foundation of this reconciliation, which follows from
      a corollary of that concept also advocated by Mayr: the proposition that the
      species is a fundamental category of biological organization. Although the
      general metapopulation lineage species concept and Mayr's popular species
      definition are commonly confused under the name "the biological species concept,"
      they are more or less clearly distinguished in Mayr's early writings on the
      subject. Virtually all modern concepts and definitions of the species category,
      not only those that require intrinsic reproductive isolation, are to be
      considered biological according to the criterion proposed by Mayr. Definitions of
      the species category that identify a particular contingent property of
      metapopulation lineages (including intrinsic reproductive isolation) as a
      necessary property of species reduce the number of metapopulation lineages that
      are to be recognized taxonomically as species, but they cause conflicts among
      alternative species definitions and compromise the status of the species as a
      basic category of biological organization.

PMID- 15851672
TI  - Mayr, Dobzhansky, and Bush and the complexities of sympatric speciation in
      Rhagoletis.
AB  - The Rhagoletis pomonella sibling species complex is a model for sympatric
      speciation by means of host plant shifting. However, genetic variation aiding the
      sympatric radiation of the group in the United States may have geographic roots.
      Inversions on chromosomes 1-3 affecting diapause traits adapting flies to
      differences in host fruiting phenology appear to exist in the United States
      because of a series of secondary introgression events from Mexico. Here, we
      investigate whether these inverted regions of the genome may have subsequently
      evolved to become more recalcitrant to introgression relative to collinear
      regions, consistent with new models for chromosomal speciation. As predicted by
      the models, gene trees for six nuclear loci mapping to chromosomes other than 1-3
      tended to have shallower node depths separating Mexican and U.S. haplotypes
      relative to an outgroup sequence than nine genes residing on chromosomes 1-3. We
      discuss the implications of secondary contact and differential introgression with
      respect to sympatric host race formation and speciation in Rhagoletis,
      reconciling some of the seemingly dichotomous views of Mayr, Dobzhansky, and Bush
      concerning modes of divergence.

PMID- 15851676
TI  - The genetic basis of reproductive isolation: insights from Drosophila.
AB  - Recent studies of the genetics of speciation in Drosophila have focused on two
      problems: (i) identifying and characterizing the genes that cause reproductive
      isolation, and (ii) determining the evolutionary forces that drove the divergence
      of these "speciation genes." Here, I review this work. I conclude that speciation
      genes correspond to ordinary loci having normal functions within species. These
      genes fall into several functional classes, although a role in transcriptional
      regulation could prove particularly common. More important, speciation genes are
      typically very rapidly evolving, and this divergence is often driven by positive
      Darwinian selection. Finally, I review recent work in Drosophila pseudoobscura on
      the possible role of meiotic drive in the evolution of the genes that cause
      postzygotic isolation.

PMID- 15851677
TI  - Chromosome speciation: humans, Drosophila, and mosquitoes.
AB  - Chromosome rearrangements (such as inversions, fusions, and fissions) may play
      significant roles in the speciation between parapatric (contiguous) or partly
      sympatric (geographically overlapping) populations. According to the "hybrid
      dysfunction" model, speciation occurs because hybrids with heterozygous
      chromosome rearrangements produce dysfunctional gametes and thus have low
      reproductive fitness. Natural selection will, therefore, promote mutations that
      reduce the probability of intercrossing between populations carrying different
      rearrangements and thus promote their reproductive isolation. This model
      encounters a disabling difficulty: namely, how to account for the spread in a
      population of a chromosome rearrangement after it first arises as a mutation in a
      single individual. The "suppressed-recombination" model of speciation points out
      that chromosome rearrangements act as a genetic filter between populations.
      Mutations associated with the rearranged chromosomes cannot flow from one to
      another population, whereas genetic exchange will freely occur between colinear
      chromosomes. Mutations adaptive to local conditions will, therefore, accumulate
      differentially in the protected chromosome regions so that parapatric or
      partially sympatric populations will genetically differentiate, eventually
      evolving into different species. The speciation model of suppressed recombination
      has recently been tested by gene and DNA sequence comparisons between humans and
      chimpanzees, between Drosophila species, and between species related to Anopheles
      gambiae, the vector of malignant malaria in Africa.

PMID- 15851675
TI  - Prospects for identifying functional variation across the genome.
AB  - The genetic factors contributing to complex trait variation may reside in
      regulatory, rather than protein-coding portions of the genome. Within noncoding
      regions, SNPs in regulatory elements are more likely to contribute to phenotypic
      variation than those in nonregulatory regions. Thus, it is important to be able
      to identify and annotate noncoding regulatory elements. DNA conservation among
      diverged species successfully identifies noncoding regulatory regions. However,
      because rapidly evolving regulatory regions will not generally be conserved
      across species, these will not detected by using purely conservation-based
      methods. Here we describe additional approaches that can be used to identify
      putative regulatory elements via signatures of nonneutral evolution. An
      examination of the pattern of polymorphism both within and between populations of
      Drosophila melanogaster, as well as divergence with its sibling species
      Drosophila simulans, across 24.2 kb of noncoding DNA identifies several
      nonneutrally evolving regions not identified by conservation. Because different
      methods tag different regions, it appears that the methods are complementary.
      Patterns of variation at different elements are consistent with the action of
      selective sweeps, balancing selection, or population differentiation. Together
      with regions conserved between D. melanogaster and Drosophila pseudoobscura, we
      tag 5.3 kb of noncoding DNA as potentially regulatory. Ninety-seven of the 408
      common noncoding SNPs surveyed are within putatively regulatory regions. If these
      methods collectively identify the majority of functional noncoding polymorphisms,
      genotyping only these SNPs in an association mapping framework would reduce
      genotyping effort for noncoding regions 4-fold.

PMID- 15851678
TI  - Speciation in birds: genes, geography, and sexual selection.
AB  - Molecular studies of speciation in birds over the last three decades have been
      dominated by a focus on the geography, ecology, and timing of speciation, a
      tradition traceable to Mayr's Systematics and the Origin of Species. However, in
      the recent years, interest in the behavioral and molecular mechanisms of
      speciation in birds has increased, building in part on the older traditions and
      observations from domesticated species. The result is that many of the same
      mechanisms proffered for model lineages such as Drosophila--mechanisms such as
      genetic incompatibilities, reinforcement, and sexual selection--are now being
      seriously entertained for birds, albeit with much lower resolution. The recent
      completion of a draft sequence of the chicken genome, and an abundance of single
      nucleotide polymorphisms on the autosomes and sex chromosomes, will dramatically
      accelerate research on the molecular mechanisms of avian speciation over the next
      few years. The challenge for ornithologists is now to inform well studied
      examples of speciation in nature with increased molecular resolution-to clone
      speciation genes if they exist--and thereby evaluate the relative roles of
      extrinsic, intrinsic, deterministic, and stochastic causes for avian
      diversification.

PMID- 15851679
TI  - Developmental plasticity and the origin of species differences.
AB  - Speciation is the origin of reproductive isolation and divergence between
      populations, according to the "biological species concept" of Mayr. Studies of
      reproductive isolation have dominated research on speciation, leaving the origin
      of species differences relatively poorly understood. Here, I argue that the
      origin of species differences, and of novel phenotypes in general, involves the
      reorganization of ancestral phenotypes (developmental recombination) followed by
      the genetic accommodation of change. Because selection acts on phenotypes, not
      directly on genotypes or genes, novel traits can originate by environmental
      induction as well as mutation, then undergo selection and genetic accommodation
      fueled by standing genetic variation or by subsequent mutation and genetic
      recombination. Insofar as phenotypic novelties arise from adaptive developmental
      plasticity, they are not "random" variants, because their initial form reflects
      adaptive responses with an evolutionary history, even though they are initiated
      by mutations or novel environmental factors that are random with respect to
      (future) adaptation. Change in trait frequency involves genetic accommodation of
      the threshold or liability for expression of a novel trait, a process that
      follows rather than directs phenotypic change. Contrary to common belief,
      environmentally initiated novelties may have greater evolutionary potential than
      mutationally induced ones. Thus, genes are probably more often followers than
      leaders in evolutionary change. Species differences can originate before
      reproductive isolation and contribute to the process of speciation itself.
      Therefore, the genetics of speciation can profit from studies of changes in gene
      expression as well as changes in gene frequency and genetic isolation.

PMID- 15851680
TI  - Critical review of host specificity and its coevolutionary implications in the
      fig/fig-wasp mutualism.
AB  - Figs (Ficus spp., Moraceae) and their pollinating wasps (Agaonidae, Chalcidoidea)
      constitute perhaps the most tightly integrated pollination mutualism that is
      known. Figs are characterized by extraordinarily high global and local species
      diversity. It has been proposed that the diversification of this mutualism has
      occurred through strict-sense coadaptation and cospeciation between pairs of fig
      and wasp species that are associated in highly specific one-to-one relationships.
      However, existing studies cast doubt on the generality of this proposition. Here,
      we review our current knowledge of the evolutionary history of the fig/fig-wasp
      mutualism. We critically examine the idea that codivergence between figs and
      their pollinators has been dominated by strict-sense cospeciation. We present
      phylogenetic and population genetic data from neotropical fig and fig wasp
      species that suggest that a more accurate model for diversification in this
      mutualism is that of groups of genetically well defined wasp species coevolving
      with genetically less well defined (frequently hybridizing) groups of figs. Last,
      we use our results to assess previously proposed hypotheses on models of
      speciation in this mutualism.

PMID- 15851681
TI  - Evolutionary animation: how do molecular phylogenies compare to Mayr's
      reconstruction of speciation patterns in the sea?
AB  - Ernst Mayr used the geography of closely related species in various stages of
      increasing divergence to "animate" the process of geographic, or allopatric,
      speciation. This approach was applied to a wide set of taxa, and a seminal paper
      by Mayr used it to explore speciation patterns in tropical sea urchins. Since
      then, taxonomic information in several of these genera has been augmented by
      detailed molecular phylogenies. We compare Mayr's animation with the phylogenies
      of eight sea urchin genera placed by Mayr into four speciation groups. True to
      Mayr's predictions, early-stage genera have on average lower species divergence
      and more polytypic species than genera in later stages. For six of these genera,
      we also have information about the evolution of the gamete recognition protein
      bindin, which is critical to reproductive isolation. These comparisons show that
      later-stage genera with many sympatric species tend to be those with rapid bindin
      evolution. By contrast, early-stage genera with few sympatric species are not
      necessarily earlier in the divergence process; they happen to be those with slow
      rates of bindin evolution. These results show that the rate of speciation in sea
      urchins does not only depend on the steady accumulation of genome divergence over
      time, but also on the rate of evolution of gamete recognition proteins. The
      animation method used by Mayr is generally supported by molecular phylogenies.
      However, the existence of multiple rates in the acquisition of reproductive
      isolation complicates placement of different genera in an evolutionary series.

PMID- 15851682
TI  - A rhodopsin exhibiting binding ability to agonist all-trans-retinal.
AB  - Rhodopsins are the members of the family of G protein-coupled receptors that have
      diverged from ligand-binding receptors into photoreceptive pigments. Vertebrate
      rhodopsins are able to bind the inverse agonist 11-cis-retinal but are unable to
      bind the agonist all-trans-retinal, indicating that vertebrate rhodopsin changed
      its binding ability during the course of molecular evolution. Here, we show that
      unlike vertebrate rhodopsin, amphioxus rhodopsin is still able to bind the
      agonist all-trans-retinal. The opsin of amphioxus rhodopsin can also bind 11-cis
      retinal to form a photoreceptive pigment that can convert to a red-shifted
      photoproduct through cis-trans isomerization of the chromophore upon photon
      absorption. The red-shifted photoproduct is the stable G protein activating
      state. Incubation of the opsin with all-trans-retinal produces a G protein
      activating state that is spectroscopically and biochemically indistinguishable
      from the red-shifted photoproduct, indicating that the opsin possesses agonist
      binding ability. The opsin exhibits an approximately 50-fold higher affinity for
      11-cis-retinal than for all-trans-retinal, and mutational analyses revealed that
      Trp-265 situated in helix VI is important for the increase in binding affinity to
      11-cis-retinal. These properties of amphioxus rhodopsin suggest that an ancestral
      rhodopsin increased the affinity for 11-cis-retinal by rearrangement of a
      structure including Trp-265 to act as a photoreceptor. In addition, an additional
      mechanism was acquired in vertebrate rhodopsin to prevent completely the binding
      of exogenous all-trans-retinal during molecular evolution.

PMID- 15851683
TI  - Solving the protein sequence metric problem.
AB  - Biological sequences are composed of long strings of alphabetic letters rather
      than arrays of numerical values. Lack of a natural underlying metric for
      comparing such alphabetic data significantly inhibits sophisticated statistical
      analyses of sequences, modeling structural and functional aspects of proteins,
      and related problems. Herein, we use multivariate statistical analyses on almost
      500 amino acid attributes to produce a small set of highly interpretable numeric
      patterns of amino acid variability. These high-dimensional attribute data are
      summarized by five multidimensional patterns of attribute covariation that
      reflect polarity, secondary structure, molecular volume, codon diversity, and
      electrostatic charge. Numerical scores for each amino acid then transform amino
      acid sequences for statistical analyses. Relationships between transformed data
      and amino acid substitution matrices show significant associations for polarity
      and codon diversity scores. Transformed alphabetic data are used in analysis of
      variance and discriminant analysis to study DNA binding in the basic helix-loop
      helix proteins. The transformed scores offer a general solution for analyzing a
      wide variety of sequence analysis problems.

PMID- 15851684
TI  - Induction of CD4+CD25+ regulatory T cells by copolymer-I through activation of
      transcription factor Foxp3.
AB  - Copolymer-I (COP-I) has unique immune regulatory properties and is a treatment
      option for multiple sclerosis (MS). This study revealed that COP-I induced the
      conversion of peripheral CD4+CD25- to CD4+CD25+ regulatory T cells through the
      activation of transcription factor Foxp3. COP-I treatment led to a significant
      increase in Foxp3 expression in CD4+ T cells in MS patients whose Foxp3
      expression was reduced at baseline. CD4+CD25+ T cell lines generated by COP-I
      expressed high levels of Foxp3 that correlated with an increased regulatory
      potential. Furthermore, we demonstrated that the induction of Foxp3 in CD4+ T
      cells by COP-I was mediated through its ability to produce IFN-gamma and, to a
      lesser degree, TGF-beta1, as shown by antibody blocking and direct cytokine
      induction of Foxp3 expression in T cells. It was evident that in vitro treatment
      and administration with COP-I significantly raised the level of Foxp3 expression
      in CD4+ T cells and promoted conversion of CD4+CD25+ regulatory T cells in wild
      type B6 mice but not in IFN-gamma knockout mice. This study provides evidence for
      the role and mechanism of action of COP-I in the induction of CD4+CD25+
      regulatory T cells in general and its relevance to the treatment of MS.

PMID- 15851685
TI  - Tetanus neurotoxin-mediated cleavage of cellubrevin impairs epithelial cell
      migration and integrin-dependent cell adhesion.
AB  - A role for endocytosis and exocytosis in cell migration has been proposed but not
      yet demonstrated. Here, we show that cellubrevin (Cb), an early endosomal v
      SNARE, mediates trafficking in the lamellipod of migrating epithelial cells and
      partially colocalizes with markers of focal contacts. Expression of tetanus
      neurotoxin, which selectively cleaves Cb, significantly reduced the speed of
      migrating epithelial cells. Furthermore, expression of tetanus neurotoxin
      enhanced the adhesion of epithelial cells to collagen, laminin, fibronectin, and
      E-cadherin; altered spreading on collagen; and impaired the recycling of beta1
      integrins. These results suggest that Cb-dependent membrane trafficking
      participates in cell motility through the regulation of cell adhesion.

PMID- 15851686
TI  - Sequence signatures and the probabilistic identification of proteins in the Myc
      Max-Mad network.
AB  - Accurate identification of specific groups of proteins by their amino acid
      sequence is an important goal in genome research. Here we combine information
      theory with fuzzy logic search procedures to identify sequence signatures or
      predictive motifs for members of the Myc-Max-Mad transcription factor network.
      Myc is a well known oncoprotein, and this family is involved in cell
      proliferation, apoptosis, and differentiation. We describe a small set of amino
      acid sites from the N-terminal portion of the basic helix-loop-helix (bHLH)
      domain that provide very accurate sequence signatures for the Myc-Max-Mad
      transcription factor network and three of its member proteins. A predictive motif
      involving 28 contiguous bHLH sequence elements found 337 network proteins in the
      GenBank NR database with no mismatches or misidentifications. This motif also
      identifies at least one previously unknown fungal protein with strong affinity to
      the Myc-Max-Mad network. Another motif found 96% of known Myc protein sequences
      with only a single mismatch, including sequences from genomes previously not
      thought to contain Myc proteins. The predictive motif for Myc is very similar to
      the ancestral sequence for the Myc group estimated from phylogenetic analyses.
      Based on available crystal structure studies, this motif is discussed in terms of
      its functional consequences. Our results provide insight into evolutionary
      diversification of DNA binding and dimerization in a well characterized family of
      regulatory proteins and provide a method of identifying signature motifs in
      protein families.

PMID- 15851687
TI  - Raft lipids as common components of human extracellular amyloid fibrils.
AB  - Amyloid fibrils are fibrillar polypeptide aggregates from several degenerative
      human conditions, including Alzheimer's and Creutzfeldt-Jakob diseases. Analysis
      of amyloid fibrils derived from various human diseases (AA, ATTR, Abeta2M,
      ALlambda, and ALkappa amyloidosis) shows that these are associated with a common
      lipid component that has a conserved chemical composition and that is
      specifically rich in cholesterol and sphingolipids, the major components of
      cellular lipid rafts. This pattern is not notably affected by the purification
      procedure, and no tight lipid interactions can be detected when preformed fibrils
      are mixed with lipids. By contrast, the early and prefibrillar aggregates formed
      in an AA amyloid-producing cell system interact with the raft marker ganglioside
      1, and amyloid formation is impaired by addition of cholesterol-reducing agents.
      These data suggest the existence of common cellular mechanisms in the generation
      of different types of clinical amyloid deposits.

PMID- 15851688
TI  - Crosslinking a lipid raft component triggers liquid ordered-liquid disordered
      phase separation in model plasma membranes.
AB  - The mechanisms by which a cell uses and adapts its functional membrane
      organization are poorly understood and are the subject of ongoing investigation
      and discussion. Here, we study one proposed mechanism: the crosslinking of
      membrane components. In immune cell signaling (and other membrane-associated
      processes), a small change in the clustering of specific membrane proteins can
      lead to large-scale reorganizations that involve numerous other membrane
      components. We have investigated the large-scale physical effect of crosslinking
      a minor membrane component, the ganglioside GM1, in simple lipid models of the
      plasma membrane containing sphingomyelin, cholesterol, and phosphatidylcholine.
      We observe that crosslinking GM1 can cause uniform membranes to phase-separate
      into large, coexistent liquid ordered and liquid disordered membrane domains. We
      also find that this lipid separation causes a dramatic redistribution of a
      transmembrane peptide, consistent with a raft model of membrane organization.
      These experiments demonstrate a mechanism that could contribute to the effects of
      crosslinking observed in cellular processes: Domains induced by clustering a
      small number of proteins or lipids might rapidly reorganize many other membrane
      proteins.

PMID- 15851689
TI  - Serine 31 phosphorylation of histone variant H3.3 is specific to regions
      bordering centromeres in metaphase chromosomes.
AB  - Histones are the fundamental components of the nucleosome. Physiologically
      relevant variation is introduced into this structure through chromatin
      remodeling, addition of covalent modifications, or replacement with specialized
      histone variants. The histone H3 family contains an evolutionary conserved
      variant, H3.3, which differs in sequence in only five amino acids from the
      canonical H3, H3.1, and was shown to play a role in the transcriptional
      activation of genes. Histone H3.3 contains a serine (S) to alanine (A)
      replacement at amino acid position 31 (S31). Here, we demonstrate by both MS and
      biochemical methods that this serine is phosphorylated (S31P) during mitosis in
      mammalian cells. In contrast to H3 S10 and H3 S28, which first become
      phosphorylated in prophase, H3.3 S31 phosphorylation is observed only in late
      prometaphase and metaphase and is absent in anaphase. Additionally, H3.3 S31P
      forms a speckled staining pattern on the metaphase plate, whereas H3 S10 and H3
      S28 phosphorylation localizes to the outer regions of condensed DNA. Furthermore,
      in contrast to phosphorylated general H3, H3.3 S31P is localized in distinct
      chromosomal regions immediately adjacent to centromeres. These findings argue for
      a unique function for the phosphorylated isoform of H3.3 that is distinct from
      its suspected role in gene activation.

PMID- 15851690
TI  - Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response.
AB  - Although aminoacyl-tRNA synthetases (ARSs) are essential for protein synthesis,
      they also function as regulators and signaling molecules in diverse biological
      processes. Here, we screened 11 different human ARSs to identify the enzyme that
      is secreted as a signaling molecule. Among them, we found that lysyl-tRNA
      synthetase (KRS) was secreted from intact human cells, and its secretion was
      induced by TNF-alpha. The secreted KRS bound to macrophages and peripheral blood
      mononuclear cells to enhance the TNF-alpha production and their migration. The
      mitogen-activated protein kinases, extracellular signal-regulated kinase and p38
      mitogen-activated protein kinase, and Galphai were determined to be involved in
      the signal transduction triggered by KRS. All of these activities demonstrate
      that human KRS may work as a previously uncharacterized signaling molecule,
      inducing immune response through the activation of monocyte/macrophages.

PMID- 15851691
TI  - Localized glucose and water influx facilitates Cryptosporidium parvum cellular
      invasion by means of modulation of host-cell membrane protrusion.
AB  - Dynamic membrane protrusions such as lamellipodia and filopodia are driven by
      actin polymerization and often hijacked by intracellular microbes to enter host
      cells. The overall rate of membrane protrusion depends on the actin
      polymerization rate and the increase of localized cell volume. Although the
      signaling pathways involving actin polymerization are well characterized, the
      molecular mechanisms regulating local cell volume associated with membrane
      protrusion are unclear. Cryptosporidium parvum, an intracellular parasite,
      depends on host-cell membrane protrusion to accomplish cell entry and form the
      parasitophorous vacuole. Here, we report that C. parvum infection of
      cholangiocytes recruits host-cell SGLT1, a Na+/glucose cotransporter, and
      aquaporin 1 (AQP1), a water channel, to the attachment site. SGLT1-dependent
      glucose uptake occurs at the attachment site. Concordantly, the region of
      attachment displays localized water influx that is inhibited by either
      suppression of AQP1 by means of AQP1-small interfering RNA (siRNA) or inhibition
      of SGLT1 by a specific pharmacologic inhibitor, phlorizin. Inhibition of SGLT1
      does not affect actin accumulation but decreases the membrane protrusion at the
      attachment site. Moreover, functional inhibition of host-cell AQP1 and SGLT1
      hampers C. parvum invasion of cholangiocytes. Thus, glucose-driven, AQP-mediated
      localized water influx is involved in the membrane protrusion during C. parvum
      cellular invasion, phenomena that may also be relevant to the mechanisms of cell
      membrane protrusion in general.

PMID- 15851692
TI  - The sacred and the secular: the life and death of Terri Schiavo.

PMID- 15851693
TI  - Pediatric clinical trials registry.

PMID- 15851694
TI  - Cardiovascular risk in patients with type 2 diabetes.

PMID- 15851695
TI  - Cardiovascular risk in patients with type 2 diabetes.

PMID- 15851696
TI  - Influenza vaccine for all?

PMID- 15851697
TI  - C. difficile: will lessons be learned?

PMID- 15851699
TI  - Earning our patients' trust.

PMID- 15851701
TI  - National consumer drug safety network launched.

PMID- 15851702
TI  - UK rejects compulsory mental health treatment.

PMID- 15851703
TI  - Patent-drug price board to review guidelines.

PMID- 15851704
TI  - New litigation limit leads to storage woes.

PMID- 15851705
TI  - Discontinuing life support in comatose patients: an example from Canadian case
      law.

PMID- 15851706
TI  - Light as a defence against fungal infection.

PMID- 15851707
TI  - When should surgery be considered for the treatment of epilepsy?

PMID- 15851708
TI  - Protecting against Clostridium difficile illness.

PMID- 15851709
TI  - Does coronary revascularization before major vascular surgery decrease mortality?

PMID- 15851710
TI  - Spontaneous expectoration of lung tumour mass.

PMID- 15851711
TI  - Outcomes in octogenarians undergoing coronary artery bypass grafting.
AB  - BACKGROUND: Although octogenarians are being referred for coronary artery bypass
      grafting (CABG) with increasing frequency, contemporary outcomes have not been
      well described. We examined data from 4 Canadian centres to determine outcomes of
      CABG in this age group. METHODS: Data for the years 1996 to 2001 were examined in
      a comparison of octogenarians with patients less than 80 years of age. Logistic
      regression analysis was used to adjust for preoperative factors and to generate
      adjusted rates of mortality and postoperative stroke. RESULTS: A total of 15,070
      consecutive patients underwent isolated CABG during the study period. Overall,
      725 (4.8%) were 80 years of age or older, the proportion increasing from 3.8% in
      1996 to 6.2% in 2001 (p for linear trend = 0.03). The crude rate of death was
      higher among the octogenarians (9.2% v. 3.8%; p < 0.001), as was the rate of
      stroke (4.7% v. 1.6%, p < 0.001). The octogenarians had a significantly greater
      burden of comorbid conditions and more urgent presentation at surgery. After
      adjustment, the octogenarians remained at greater risk for in-hospital death
      (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.95-3.57) and stroke (OR
      3.25, 95% CI 2.15-4.93). Mortality declined over time for both age groups (p for
      linear trend < 0.001 for both groups), but the incidence of postoperative stroke
      did not change (p for linear trend = 0.61 [age < 80 years] and 0.08 [age > or =
      80 years]). Octogenarians who underwent elective surgery had crude and adjusted
      rates of death (OR 1.31, 95% CI 0.60-2.90) and stroke (OR 1.59, 95% CI 0.57-4.44)
      that were higher than but not significantly different from those for non
      octogenarians who underwent elective surgery. INTERPRETATION: In this study,
      rates of death and stroke were higher among octogenarians, although the adjusted
      differences in mortality over time were decreasing. The rate of adverse outcomes
      in association with elective surgery was similar for older and younger patients.

PMID- 15851712
TI  - Effectiveness of statins for secondary prevention in elderly patients after acute
      myocardial infarction: an evaluation of class effect.
AB  - BACKGROUND: Clinical trials have shown the benefits of statins after acute
      myocardial infarction (AMI). However, it is unclear whether different statins
      exert a similar effect in reducing the incidence of recurrent AMI and death when
      used in clinical practice. METHODS: We conducted a retrospective cohort study
      (1997-2002) to compare 5 statins using data from medical administrative databases
      in 3 provinces (Quebec, Ontario and British Columbia). We included patients aged
      65 years and over who were discharged alive after their first AMI-related
      hospital stay and who began statin treatment within 90 days after discharge. The
      primary end point was the combined outcome of recurrent AMI or death from any
      cause. The secondary end point was death from any cause. Adjusted hazard ratios
      (HRs) for each statin compared with atorvastatin as the reference drug were
      estimated using Cox proportional hazards regression analysis. RESULTS: A total of
      18,637 patients were prescribed atorvastatin (n = 6420), pravastatin (n = 4480),
      simvastatin (n = 5518), lovastatin (n = 1736) or fluvastatin (n = 483). Users of
      different statins showed similar baseline characteristics and patterns of statin
      use. The adjusted HRs (and 95% confidence intervals) for the combined outcome of
      AMI or death showed that each statin had similar effects when compared with
      atorvastatin: pravastatin 1.00 (0.90-1.11), simvastatin 1.01 (0.91-1.12),
      lovastatin 1.09 (0.95-1.24) and fluvastatin 1.01 (0.80-1.27). The results did not
      change when death alone was the end point, nor did they change after adjustment
      for initial daily dose or after censoring of patients who switched or stopped the
      initial statin treatment. INTERPRETATION: Our results suggest that, under current
      usage, statins are equally effective for secondary prevention in elderly patients
      after AMI.

PMID- 15851713
TI  - Are the benefits of statins a class effect?

PMID- 15851715
TI  - Patient page. Untreated hypertension can lead to memory loss by cutting down on
      blood flow to the brain.

PMID- 15851716
TI  - Triple trouble: cognitive deficits from hepatitis C, HIV, and methamphetamine.

PMID- 15851714
TI  - Behavioural treatments for chronic systemic inflammation: effects of dietary
      weight loss and exercise training.
AB  - Persistent low-grade inflammation, as indicated by higher circulating levels of
      inflammatory mediators such as C-reactive protein, interleukin-6 and tumour
      necrosis factor-alpha, is a strong risk factor for several chronic diseases.
      There are data indicating that decreasing energy intake and increasing physical
      activity may be effective therapies for reducing overall inflammation. Evidence
      is strong that circulating levels of inflammatory markers are elevated with total
      and abdominal obesity, possibly owing to a higher secretion rate of cytokines by
      adipose tissue in obese people. Moreover, very-low-energy dietary weight loss
      reduces both circulating markers of inflammation and adipose-tissue cytokine
      production. Data from several large population-based cohorts show an inverse
      association between markers of systemic inflammation and physical activity or
      fitness status; small-scale intervention studies support that exercise training
      diminishes inflammation. Dietary weight loss plus exercise is likely more
      effective than weight reduction alone in reducing inflammation. To date, data
      from randomized, controlled trails designed to definitively test the effects of
      weight loss or exercise training, or both, on inflammation are limited. Future
      studies are required to define the amount of weight loss needed for clinically
      meaningful reductions of inflammation; in addition, fully powered and controlled
      studies are necessary to clarify the effect of exercise training on chronic,
      systemic inflammation.

PMID- 15851717
TI  - Improved outcome with aggressive treatment of hyperglycemia: hype or hope?

PMID- 15851718
TI  - Combining carotid endarterectomy with coronary bypass surgery: is it worth the
      risk?

PMID- 15851719
TI  - Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale.
AB  - The symptoms, severity, and course of multiple sclerosis (MS) vary among
      patients, leading to complex treatment issues. In recent years, research has
      focused on specific adhesion molecules that participate in the activation and
      function of lymphocytes, especially the migration of these cells to sites of
      inflammation. In particular, the integrin, very late activation antigen (VLA)-4,
      has been implicated in mediating adhesion and migration of immune cells through
      interaction with its ligand, vascular cell adhesion molecule (VCAM)-1. VLA-4 is
      comprised of alpha4/beta1 and is critical in mediating Th-1 cell migration in the
      animal model of MS, experimental autoimmune encephalomyelitis, and has been the
      target of several recent clinical trials in MS. The humanized monoclonal antibody
      to alpha4 integrin, natalizumab (Tysabri, Biogen Idec/Elan), was recently
      approved in the United States for the treatment of relapsing MS. The authors
      discuss the mechanisms by which alpha4 integrins alter lymphocyte function as a
      rationale for anti-alpha4 integrin use in MS.

PMID- 15851720
TI  - Hepatitis C augments cognitive deficits associated with HIV infection and
      methamphetamine.
AB  - OBJECTIVE: To examine the contribution of hepatitis C virus (HCV) infection to
      neurocognitive dysfunction in individuals with comorbid HIV infection or
      methamphetamine (METH) dependence. METHODS: Neurocognitive functioning was
      examined in 430 study participants who were either normal controls or had HCV
      infection, HIV infection, history of METH dependence, or combinations of these
      factors as risks for cognitive deficits. RESULTS: Rates of global and domain
      specific neuropsychological (NP) impairment increased with the number of risk
      factors. HCV serostatus was a significant predictor of NP performance both
      globally and in the areas of learning, abstraction, and motor skills, with trends
      in speeded information processing and delayed recall. HCV serostatus did not
      predict scores in attention/working memory or verbal fluency. CONCLUSION:
      Hepatitis C virus infection contributes to the neuropsychological deficits
      observed among HIV-infected and stimulant-dependent populations.

PMID- 15851721
TI  - Insulin therapy protects the central and peripheral nervous system of intensive
      care patients.
AB  - OBJECTIVE: To investigate the effectiveness of maintaining blood glucose levels
      below 6.1 mmol/L with insulin as prevention of secondary injury to the central
      and peripheral nervous systems of intensive care patients. METHODS: The authors
      studied the effect of intensive insulin therapy on critical illness
      polyneuropathy (CIPNP), assessed by weekly EMG screening, and its impact on
      mechanical ventilation dependency, as a prospectively planned subanalysis of a
      large randomized, controlled trial of 1,548 intensive care patients. In the 63
      patients admitted with isolated brain injury, the authors studied the impact of
      insulin therapy on intracranial pressure, diabetes insipidus, seizures, and long
      term rehabilitation at 6 and 12 months follow-up. RESULTS: Intensive insulin
      therapy reduced ventilation dependency (p = 0.0007; Mantel-Cox log rank test) and
      the risk of CIPNP (p < 0.0001). The risk of CIPNP among the 405 long-stay (> or
      =7 days in intensive care unit) patients was lowered by 49% (p < 0.0001). Of all
      metabolic and clinical effects of insulin therapy, and corrected for known risk
      factors, the level of glycemic control independently explained this benefit (OR
      for CIPNP 1.26 [1.09 to 1.46] per mmol blood glucose, p = 0.002). In turn,
      prevention of CIPNP explained the ability of intensive insulin therapy to reduce
      the risk of prolonged mechanical ventilation (OR 3.75 [1.49 to 9.39], p = 0.005).
      In isolated brain injury patients, intensive insulin therapy reduced mean (p =
      0.003) and maximal (p < 0.0001) intracranial pressure while identical cerebral
      perfusion pressures were obtained with eightfold less vasopressors (p = 0.01).
      Seizures (p < 0.0001) and diabetes insipidus (p = 0.06) occurred less frequently.
      At 12 months follow-up, more brain-injured survivors in the intensive insulin
      group were able to care for most of their own needs (p = 0.05). CONCLUSIONS:
      Preventing even moderate hyperglycemia with insulin during intensive care
      protected the central and peripheral nervous systems, with clinical consequences
      such as shortening of intensive care dependency and possibly better long-term
      rehabilitation.

PMID- 15851722
TI  - Heads down: flat positioning improves blood flow velocity in acute ischemic
      stroke.
AB  - BACKGROUND: Acute stroke patients are routinely positioned with the head of the
      bed (HOB) elevated at 30 degrees despite lack of evidence for increased
      intracranial pressure. OBJECTIVES: To determine the effect of HOB positions in
      real time on residual blood flow velocity in acutely occluded arteries causing
      stroke and whether resistance to residual flow increased with lower HOB
      positions. METHODS: In a repeated-measures quasi-experiment, the effect of 30,
      15, and 0 degrees HOB on middle cerebral artery (MCA) mean flow velocity (MFV) in
      patients with acute (<24 hours) ischemic stroke was measured with transcranial
      Doppler using MFV and pulsatility index (PI) of the residual flow signals at the
      site of persisting acute occlusion. RESULTS: Twenty patients were evaluated (mean
      age 60 +/- 15 years; median NIH Stroke Scale [NIHSS] score 14 points). MCA MFV
      increased in all patients with lowering head position (maximum absolute MFV value
      increase 27 cm/s, range 5 to 96% from baseline values at 30 degrees). On average,
      MCA MFV increased 20% (12% from 30 to 15 degrees and 8% from 15 to 0 degrees; p <
      or = 0.025). Mean arterial pressure and heart rate were unchanged throughout the
      intervention. PI remained unchanged (mean values 0.89 at 30 degrees elevation,
      0.91 at 15 degrees elevation, and 0.83 at 0 degrees elevation) at each HOB
      position, indicating no increase in resistance to blood flow. Immediate
      neurologic improvement (average 3 NIHSS motor points) occurred in three patients
      (15%) after lowering head position. CONCLUSION: Acute ischemic stroke patients
      may benefit from lower head-of-the-bed positions to promote residual blood flow
      to ischemic brain tissue.

PMID- 15851723
TI  - Reduced cerebral blood flow response and compensation among patients with
      untreated hypertension.
AB  - OBJECTIVE: To determine whether memory performance in hypertensive subjects
      induces diminished parietal and prefrontal blood flow activation relative to
      normotensive subjects but compensatory amygdala/hippocampal activation. METHODS:
      Thirty-seven untreated hypertensive subjects and 59 normotensive control subjects
      performed in two memory and one sensorimotor task while global and regional
      cerebral blood flow (rCBF) was assessed with [15O]water and PET.
      Neuropsychological, carotid artery ultrasound, and MRI assessments were obtained.
      RESULTS: When they were engaged in memory tasks, increases of CBF in hypertensive
      subjects were less than in normotensive subjects in the posterior parietal area,
      as expected; blunted responses were also shown within the middle posterior
      arterial watershed and thalamus. Relative to all other participants, hypertensive
      subjects that performed relatively well on verbal memory showed an enhanced rCBF
      response in the right amygdala/hippocampus. Furthermore, hypertensive, but not
      normotensive, subjects showed task-induced rCBF in the amygdala/hippocampal area
      that was significantly correlated with task-induced prefrontal rCBF. No
      confounding influences were identified from carotid artery or MRI measures.
      CONCLUSIONS: Memory performance in hypertensive individuals is related to a
      blunted regional cerebral blood flow (rCBF) response, particularly in parietal
      cortex. Potentially compensatory rCBF responses appear to occur in midbrain and
      correlate with prefrontal rCBF.

PMID- 15851724
TI  - Apo(a) size in ischemic stroke: relation with subtype and severity on hospital
      admission.
AB  - OBJECTIVE: To determine the distribution of apolipoprotein (a) (apo[a]) isoforms
      and their relation to the clinical severity of different ischemic stroke
      subtypes. METHODS: Ninety-four hospital cases with a first-ever ischemic stroke
      and 188 randomly selected control subjects matched for age, gender, and ethnicity
      were enrolled. Stroke etiology was defined according to Trial of Org 10172 in
      Acute Stroke Treatment criteria. NIH Stroke Scale (NIHSS) was used to assess the
      severity of stroke on admission. RESULTS: In univariate analysis, the presence of
      at least one small apo(a) isoform was associated with ischemic stroke in men (p =
      0.02) but not in women (p = 0.33). After allowance for age, gender and
      traditional vascular risk factors, subjects carrying at least one small apo(a)
      isoform were at increased risk of atherothrombotic stroke (odds ratio [OR] 7.1,
      95% CI 2.8 to 17.5, p = 0.00001) but not of lacunar infarction (OR 1.1, 95% CI
      0.5 to 2.7, p = 0.78). Multivariate logistic regression analysis revealed that in
      the atherothrombotic stroke group, the presence of at least one small-sized
      apo(a) phenotype was associated with an NIHSS score > or =6 (OR 13.6, 95% CI 1.6
      to 111.9, p = 0.015). CONCLUSION: Small apolipoprotein (a) isoforms distinguish
      atherothrombotic stroke from lacunar infarction and are associated with the
      severity of atherothrombotic stroke.

PMID- 15851725
TI  - Inferior predilection of Lisch nodules with ptosis.

PMID- 15851726
TI  - Serum inflammatory proteins and cognitive decline in older persons.
AB  - OBJECTIVE: To assess whether serum levels of the inflammatory proteins alpha(1)
      antichymotrypsin (ACT), C-reactive protein (CRP), interleukin-6 (IL-6), and
      albumin are associated with cognitive decline in older persons. METHODS: The
      study sample consisted of 1,284 participants in the Longitudinal Aging Study
      Amsterdam, aged 62 to 85 years. Cognition was assessed on general cognition (Mini
      Mental State Examination [MMSE]), memory (Auditory Verbal Learning Test), fluid
      intelligence (Raven's Colored Progressive Matrices), and information-processing
      speed (Coding Task) at baseline and at 3-year follow-up. RESULTS: The highest
      tertile of ACT was associated with an increased risk of decline on the MMSE (age
      , sex-, education-adjusted odds ratio [OR] 1.60; 95% CI: 1.05 to 2.43) but not on
      any other cognitive test score. CRP, IL-6, and albumin were not associated with
      cognitive decline on any cognitive test in our study. CONCLUSIONS: This
      population-based study showed that the serum inflammatory protein alpha1
      antichymotrypsin is associated with cognitive decline in older persons, whereas C
      reactive protein, interleukin-6, and albumin are not.

PMID- 15851727
TI  - Impact of plasma lipids and time on memory performance in healthy elderly without
      dementia.
AB  - OBJECTIVE: To examine the association of plasma lipid levels to changes in
      cognitive function in elderly subjects without dementia. METHODS: The authors
      examined changes in performance in tests of memory, visuospatial/cognitive, and
      language abilities in 1,147 elderly individuals without dementia or cognitive
      impairment at baseline followed for 7 years using generalized estimating
      equations. RESULTS: Performance in all cognitive domains declined significantly
      over time, while there was no association between levels of any plasma lipid or
      lipid lowering treatment and memory, cognitive/visuospatial, or language
      performance at any interval. Higher age at baseline was related to lower scores
      in all three domains at each interval, while higher education and white ethnicity
      were associated with higher scores in all domains. Analyses relating plasma
      lipids to performance in color trails tests using proportional hazards regression
      showed no association. In subsequent analyses excluding subjects with incident
      dementia, memory performance declined over time, while cognitive/visuospatial and
      language performance did not. Higher plasma high density lipoprotein and total
      cholesterol were associated with higher scores in language performance at
      baseline; this domain declined faster among individuals with higher total
      cholesterol, but this result was not significant after taking multiple
      comparisons into account. Plasma triglycerides, low density lipoprotein, or
      treatment with lipid lowering agents were not associated with changes in
      cognitive performance. CONCLUSIONS: Plasma lipid levels or treatment with lipid
      lowering agents in the elderly were not associated with changes in cognitive
      function.

PMID- 15851729
TI  - Disorganized somatotopy in the putamen of patients with focal hand dystonia.
AB  - OBJECTIVE: To explore the selectivity of neuronal somatotopic representation in
      the striatum of patients with unilateral task-specific dystonia of the right arm.
      MATERIALS AND METHODS: The authors used fMRI in 14 right-handed dystonic subjects
      to examine putaminal organization. Subjects performed flexion/extension of the
      right and left fingers and toes, and contraction of the lips. RESULTS: Compared
      to healthy volunteer subjects, dystonic subjects had altered somatotopic
      organization in the left putamen, contralateral to the affected hand. Disease
      severity correlated with underactivation and decreased distance between right
      hand and lip representations. In the right putamen, ipsilateral to the affected
      hand, the somatotopic organization was not altered but disease severity also
      correlated with reduced distances between limbs. CONCLUSION: In dystonia there
      may be a dedifferentiation of the normally segregated cortico-subcortical
      sensorimotor maps in the putamen, which may contribute to the loss of functional
      selectivity of muscle activity observed in these dystonic subjects.

PMID- 15851728
TI  - The natural history of temporal variant frontotemporal dementia.
AB  - BACKGROUND: The temporal variant of frontotemporal dementia (tvFTD) features
      asymmetric anterior temporal/amygdala degeneration as well as ventromedial
      frontal, insular, and inferoposterior temporal involvement. Left temporal atrophy
      has been linked to loss of semantic knowledge, whereas behavioral symptoms
      dominate the right temporal variant. OBJECTIVE: To investigate the first symptoms
      and the timing of subsequent symptoms in patients with left versus right tvFTD.
      METHODS: Twenty-six patients with tvFTD were identified. Six had right > left
      temporal atrophy (right temporal lobe variant [RTLV]) and were matched with six
      having comparable left > right temporal atrophy (left temporal lobe variant
      [LTLV]). Clinical records were reviewed to generate individualized symptom
      chronologies. RESULTS: In all patients, first symptoms involved semantics (4/6
      LTLV, 1/6 RTLV), behavior (4/6 RTLV, 1/6 LTLV), or both (1 LTLV, 1 RTLV).
      Semantic loss began with anomia, word-finding difficulties, and repetitive
      speech, whereas the early behavioral syndrome was characterized by emotional
      distance, irritability, and disruption of physiologic drives (sleep, appetite,
      libido). After an average of 3 years, patients developed whichever of the two
      initial syndromes--semantic or behavioral--that they lacked at onset. A third
      stage, 5 to 7 years from onset, saw the emergence of disinhibition, compulsions,
      impaired face recognition, altered food preference, and weight gain. Compulsions
      in LTLV were directed toward visual, nonverbal stimuli, whereas patients with
      RTLV were drawn to games with words and symbols. CONCLUSIONS: The temporal
      variant of frontotemporal dementia follows a characteristic cognitive and
      behavioral progression that suggests early spread from one anterior temporal lobe
      to the other. Later symptoms implicate ventromedial frontal, insular, and
      inferoposterior temporal regions, but their precise anatomic correlates await
      confirmation.

PMID- 15851731
TI  - Cognitive status correlates with neuropathologic stage in Parkinson disease.
AB  - OBJECTIVE: To study the association of cognitive status with the stages of a
      published neuropathologic staging procedure for sporadic Parkinson disease (PD)
      in a cohort of 88 patients with PD from a single neurologic unit. None had
      received the clinical diagnosis of dementia with Lewy bodies (DLB). METHODS: The
      authors assessed Lewy neurites/bodies (LNs/LBs) immunoreactive for alpha
      synuclein semiquantitatively in sections from 18 brain regions. In silver-stained
      sections and sections immunostained for tau and beta-amyloid protein, the authors
      semiquantitatively evaluated comorbidities potentially contributing to cognitive
      decline, e.g., Alzheimer disease (AD), argyrophilic grain disease (AGD), and
      cerebral vascular disease. The authors analyzed four Mini-Mental State
      Examination (MMSE) subgroups ranging from marginally impaired cognition to severe
      dementia using nonparametric tests. RESULTS: It was possible to assign all
      patients to one of the PD stages. MMSE scores correlated with neuropathologic
      stages (p < 0.005) and this association showed a linear trend (p < 0.025). Median
      MMSE test scores for women were lower than those for men. Cognitively impaired
      individuals displayed higher stages of AD-related neurofibrillary pathology (p <
      0.05) and beta-amyloid deposition (p < 0.05) than cognitively unimpaired persons.
      MMSE scores did not correlate significantly with AGD, disease duration, age at
      disease onset, or age at death. Hoehn and Yahr scores, however, correlated with
      PD stages (p < 0.0005) and MMSE scores (p < 0.0005). CONCLUSIONS: The decrease in
      median Mini-Mental State Examination scores between PD stages 3 to 6 indicates
      that the risk of developing dementia increases with disease progression. In some
      individuals, however, cognitive decline can develop in the presence of mild
      Parkinson disease-related cortical pathology and, conversely, widespread cortical
      lesions do not necessarily lead to cognitive decline.

PMID- 15851730
TI  - The pathology of the substantia nigra in Alzheimer disease with extrapyramidal
      signs.
AB  - BACKGROUND: Extrapyramidal signs (EPS) are common in Alzheimer disease (AD) and
      increase in prevalence as AD advances. The neuropathologic substrate responsible
      for EPS in AD remains to be fully characterized. METHODS: Subjects had a clinical
      diagnosis of AD confirmed by neuropathologic examination. EPS during life were
      documented by clinical methods assessing bradykinesia, cogwheel rigidity, rest
      tremor, and parkinsonian gait. Subjects with EPS and previous neuroleptic
      exposure were excluded. Twenty-eight subjects were in the EPS group and 104
      subjects were without EPS. Neuron loss, alpha-synuclein (ASYN)-labeled pathology,
      and tau-labeled pathology in the substantia nigra were measured using
      semiquantitative techniques such that higher scores represented increased
      pathologic burden. RESULTS: Presence of nigral ASYN-labeled pathology was more
      common (50 vs 28.9%; p < 0.05) in the EPS group than in those without EPS. There
      was more nigral neuron loss in the EPS group (1.50 vs 1.11 in no-EPS group; p <
      0.05). Tau-labeled burden was not different by group comparisons; however, EPS
      onset at later stages of dementia severity was associated with increased tau
      labeled pathology (Kendall tau-B = 0.48, p < 0.01) and this association remained
      after controlling for dementia severity at death. Additionally, moderate to
      severe tau burden was more common in the subgroup with "pure AD" (definite AD
      without other neuropathology) with EPS (81.8%) than cases without EPS (49.0%; p <
      0.05). Four subjects with EPS (14.3%) had little to no significant nigral
      pathologic changes. CONCLUSIONS: Clinically detected extrapyramidal signs (EPS)
      in Alzheimer disease (AD) are associated with substantia nigra pathology
      including alpha-synuclein aggregation, hyperphosphorylated tau accumulation, and
      neuron loss that may account for the increasing prevalence of EPS as AD
      progresses. In some cases, limited nigral pathology suggests extranigral factors
      in the clinical symptoms of EPS.

PMID- 15851733
TI  - Spreading of sudomotor axon reflexes in human skin.
AB  - BACKGROUND: Acetylcholine (ACh) activates both sudomotor fibers and primary
      afferent nociceptors. This leads to sudomotor and vasodilator axon reflexes,
      which can be diminished, for example, in neuropathies. In some neuropathies,
      however, there is increased axon reflex sweating, a response pattern that has
      never been observed for vasodilator flares. OBJECTIVES: To compare both types of
      axon reflexes and to elucidate possible differences. METHODS: In healthy young
      male subjects, sweat response and flare reaction in response to ACh were
      quantified. Constant-current iontophoresis (300 mC) of ACh was performed on the
      lateral lower legs. The sudomotor axon reflex was visualized with iodine starch
      staining, and the sweat response was quantified with capacitance hygrometry
      (quantitative sudomotor axon reflex test [QSART]). The vasodilator flare was
      visualized and quantified by laser Doppler imaging. All measurements were
      performed during and for 10 minutes after finishing the iontophoresis. RESULTS:
      The sudomotor axon reflex area increased from 30.6 cm2 at the end of the
      iontophoresis to 39.2 cm2 (p < 0.001) 10 minutes later, while QSART response had
      already decreased. Flare size and flare intensity remained nearly constant during
      the observation period. CONCLUSION: Despite fast cleavage of acetylcholine by
      cholinesterases, sudomotor axon reflexes spread in the skin, indicating a
      possible peripheral amplification of sweating.

PMID- 15851732
TI  - Cystic leukoencephalopathy without megalencephaly: a distinct disease entity in
      15 children.
AB  - OBJECTIVE: To describe a distinctive syndrome of nonprogressive encephalopathy,
      normo- or microcephaly, and early onset of severe psychomotor impairment in 15
      white patients, including two siblings and two first cousins. METHODS AND
      RESULTS: MRI revealed bilateral cysts in the anterior part of the temporal lobe
      and white matter abnormalities with pericystic abnormal myelination and symmetric
      lesions in frontal and occipital periventricular regions. None of the usual
      inborn errors of metabolism/infectious diseases associated with
      leukoencephalopathy and bilateral anterior temporal lobe cysts were detected.
      CONCLUSIONS: These patients' clinical signs and cranial MRI abnormalities are
      strikingly similar and may represent a distinctive disease with autosomal
      recessive inheritance: cystic leukoencephalopathy without megalencephaly.

PMID- 15851734
TI  - Cognitive functioning in children and adolescents with multiple sclerosis.
AB  - OBJECTIVE: To examine cognitive functioning in children with multiple sclerosis
      (MS). METHODS: The authors examined the neuropsychological profile of 37 children
      with a diagnosis of clinically definite MS and assessed the associations between
      cognitive function and clinical features. RESULTS: Of 37 children and adolescents
      evaluated, 35% demonstrated significant cognitive impairment. Cognitive
      functioning was strongly related to several clinical variables, including current
      Expanded Disability Status Scale, total number of relapses, and total disease
      length. The consequences of MS adversely affected academic functioning in over a
      third of the children. CONCLUSIONS: Cognitive deficits occur in children with
      multiple sclerosis. Comprehensive treatment planning should involve recognition
      that they may require academic accommodations for their education.

PMID- 15851735
TI  - Mild glycine encephalopathy (NKH) in a large kindred due to a silent exonic GLDC
      splice mutation.
AB  - BACKGROUND: Classic neonatal-onset glycine encephalopathy (GE) is devastating and
      life threatening. Milder, later onset variants have been reported but were
      usually sporadic and incompletely defined. OBJECTIVE: To determine the clinical
      and biochemical phenotype and molecular basis of mild GE in nine children from a
      consanguineous Israeli Bedouin kindred. METHODS: Genomic DNA was screened for
      GLDC, AMT, and GCSH gene mutations. GLDC expression in lymphoblasts was studied
      by Northern blot and reverse transcriptase PCR analysis. RESULTS: Clinical
      features included hypotonia, abnormal movements, convulsions, and moderate mental
      retardation with relative sparing of gross motor function, activities of daily
      living skills, and receptive language. Aggression and irritability were
      prominent. CSF-to-plasma glycine ratio was mildly to moderately elevated. All
      nine patients were homozygous and their parents heterozygous for a novel,
      translationally silent GLDC exon 22 transversion c.2607C>A. Lymphoblast GLDC mRNA
      levels were considerably reduced. Three aberrantly spliced cDNA species were
      identified: exon 22 and exon 22 to 23 skipping, and insertion of an 87-base pair
      cryptic exon. Homozygosity for c.2607C>A was also identified in an unrelated but
      haplotypically identical patient with an unusually favorable outcome despite
      severe neonatal-onset GE. Mutation analysis enabled prenatal diagnosis of three
      unaffected and one affected pregnancies. CONCLUSIONS: The mutation in this
      kindred led to missplicing and reduced GLDC (glycine decarboxylase) expression.
      The 4 to 6% of normally spliced GLDC mRNA in the patients may account for their
      relatively favorable clinical outcome compared with patients with classic glycine
      encephalopathy.

PMID- 15851736
TI  - Executive dysfunction in hyperhomocystinemia responds to homocysteine-lowering
      treatment.
AB  - An elevated serum homocysteine level is a risk factor for the development of
      cognitive impairment. Reported is a late-onset case of hyperhomocystinemia due to
      a vitamin B12 metabolic deficit (cobalamin C) with cognitive impairment,
      primarily in frontal/executive function. After homocysteine-lowering therapy, the
      patient's functional and neuropsychological status improved in conjunction with a
      decrease in leukoariosis on his MRI scan. These findings suggest that
      homocysteine-related cognitive impairment may be partially reversible.

PMID- 15851737
TI  - Simultaneous carotid endarterectomy and coronary artery bypass surgery in Canada.
AB  - Stroke neurologists are commonly asked to review patients who require coronary
      artery bypass grafting (CABG) but who also have comorbid severe carotid stenosis;
      such patients may be offered simultaneous carotid endarterectomy (CEA). In
      Canada, 0.51% of CABG procedures were combined CEA-CABG. The adjusted stroke and
      death rate was 2.67-fold greater in the combined CEA-CABG group compared to CABG
      alone. Randomized trials of the combined procedure are needed.

PMID- 15851738
TI  - Somatotopically located motor fibers in corona radiata: evidence from subcortical
      small infarcts.
AB  - Using T2-weighted MRI, we measured the relative anteroposterior distance of small
      corona radiata infarcts in 54 patients who had disproportionate weakness in the
      bulbar (Group A), arm (Group B), and leg (Group C) muscles. The lesions were
      differently (p < 0.01) located: Group A, most were located anteriorly; Group B,
      most were in the middle; and Group C, most were located posteriorly. These
      results suggest that motor fibers are somatotopically arranged in the human
      corona radiata.

PMID- 15851739
TI  - Neurologic symptoms are common during gestation and puerperium in CADASIL.
AB  - Based on a structured questionnaire and medical records, the authors found that
      12 of 25 mothers with cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) with the R133C NOTCH3 mutation had had
      neurologic symptoms in 17 of their 43 pregnancies, most commonly hemiparesthesia
      (76%), hemiparesis (36%), aphasia (65%), and visual disorders (47%). In 82% of
      the patients, the symptoms were the first manifestation of CADASIL. The symptoms
      were most common during puerperium and in patients older than age 30.

PMID- 15851740
TI  - Optociliary shunt vessels.

PMID- 15851741
TI  - EGFR tyrosine kinase domain mutations in human gliomas.
AB  - Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor
      effective in patients with lung cancer with mutations in exons 19 and 21 of the
      EGFR tyrosine kinase domain. In this study, the authors tested the presence of
      such mutations in 95 gliomas including glioblastomas, anaplastic
      oligodendrogliomas, and low-grade gliomas. No mutation was found, which suggests
      that the biology of EGFR in gliomas is different from lung cancer and that this
      may be a factor in the resistance of glioblastomas to gefitinib.

PMID- 15851742
TI  - Developmental origin of subependymal giant cell astrocytoma in tuberous sclerosis
      complex.
AB  - Children with tuberous sclerosis complex (TSC) harbor developmental brain
      abnormalities (cortical tubers) and low-grade tumors (subependymal giant cell
      astrocytomas [SEGAs]). Using gene expression profiling to identify neuroglial
      differentiation markers in Tsc1 conditional knockout mice, the authors
      demonstrate that giant cells of SEGAs aberrantly express similar neuroglial
      differentiation markers as do cortical tubers. These results suggest that both
      tubers and SEGAs result from related defects in progenitor cell differentiation
      during brain development.

PMID- 15851743
TI  - Nocturnal activity with nighttime pergolide in Parkinson disease: a controlled
      study using actigraphy.
AB  - Pergolide is a dopamine agonist that improves Parkinson disease but is associated
      with dose-dependent sleepiness. This study evaluates the effect of a nighttime
      dose of 1 mg of pergolide on actigraphic measures of sleep using a randomized,
      double-blind, placebo-controlled study design. The pergolide group (n = 10)
      worsened in actigraphic measures of sleep efficiency and sleep fragmentation vs
      the placebo group (n = 12). Side effects were more frequent in the pergolide
      group.

PMID- 15851744
TI  - Tibial nerve SEPs localized the lesion site in a patient with early tabes
      dorsalis.
AB  - There is controversy regarding the initial pathology of tabes dorsalis. In a
      patient with early tabes dorsalis, tibial nerve somatosensory evoked potentials
      elicited normal P15, a delayed traveling peak in the lumbar bipolar leads, and
      absent subsequent components. Based on the comparison with normative data and
      stimulation at different intensities, the authors conclude that only the slower
      conducting antidromic motor volleys are preserved, whereas the dorsal root is
      damaged at its distal end.

PMID- 15851745
TI  - A novel mutation (G114V) in the prion protein gene in a family with inherited
      prion disease.
AB  - Inherited prion diseases are characterized by mutations in the PRNP gene encoding
      the prion protein (PrP). We report a novel missense mutation in the PRNP gene
      (resulting in a G114V mutation in PrP) in members of a Uruguayan family with
      clinical and histopathologic features of prion disease. Affected individuals were
      characterized by an early age at onset, initial neuropsychiatric symptoms, late
      dementia with prominent pyramidal and extrapyramidal symptoms, and long disease
      duration.

PMID- 15851746
TI  - A family with early-onset and rapidly progressive X-linked spinal and bulbar
      muscular atrophy.
AB  - Spinal and bulbar muscular atrophy (SBMA) is an X-linked, late-onset
      neuroendocrine disorder resulting from an expansion of a CAG repeat in the
      androgen receptor gene. Reported here is a detailed phenotypic study in a series
      of seven patients from the same family with SBMA with 50 to 54 CAG repeats,
      juvenile onset (mean age at onset 13 years [8 to 15 years]), and rapid
      progression leading to compromised ambulation in the mid-20s.

PMID- 15851747
TI  - Leukoencephalopathy with ataxia, hypodontia, and hypomyelination.
AB  - The authors describe four unrelated girls with a distinctive neurologic disorder
      with early-onset progressive ataxia and hypodontia with a characteristic pattern
      of delayed dentition. Cerebral MRI shows hypomyelinated white matter and
      cerebellar atrophy; 1H-MRS of white matter reveals a marked elevation of myo
      inositol.

PMID- 15851748
TI  - Respiratory failure in Pompe disease: treatment with noninvasive ventilation.
AB  - In this study, noninvasive ventilation (NIV) was prospectively applied to eight
      patients (35.8 +/- 11.4 years) with late-onset Pompe disease and respiratory
      failure apparent from severe restrictive lung disease, nocturnal hypoxemia (83 +/
      8%), and daytime hypercapnia (66.7 +/- 17.9 mm Hg). The impact of NIV on
      respiratory function was followed for 34 +/- 17 months. Despite further decrease
      of vital capacity and inspiratory muscle strength, NIV normalized oxygen
      saturation during sleep (96 +/- 1%), daytime carbon dioxide tensions (44.1 +/-
      3.6 mm Hg), and symptoms.

PMID- 15851749
TI  - Neuropathy resembling CIDP in patients receiving tumor necrosis factor-alpha
      blockers.
AB  - Tumor necrosis factor-alpha (TauNuFalpha) blockers are effective in the treatment
      of inflammatory arthritis but can induce autoimmune disorders including multiple
      sclerosis. Described are two patients who developed chronic inflammatory
      demyelinating polyneuropathy after initiation of anti-TNFalpha treatment.

PMID- 15851750
TI  - Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP.
AB  - To identify clinical and electrophysiologic features related to IV immunoglobulin
      (IVIg) responsiveness in chronic inflammatory demyelinating polyneuropathy
      (CIDP), the authors conducted a multicenter study on 312 patients with CIDP (199
      responders and 113 nonresponders). Muscle atrophy and decreased compound muscle
      action potential were pronounced in nonresponders of IVIg. Male gender, longer
      disease duration, and slow progression of symptoms were also associated with IVIg
      unresponsiveness. Features suggesting axonal dysfunction in peripheral nerves
      indicated IVIg unresponsiveness in CIDP.

PMID- 15851751
TI  - Cerebrotendinous xanthomatosis: a treatable ataxia.

PMID- 15851752
TI  - Brachial amyotrophic diplegia associated with a novel SOD1 mutation (L106P).

PMID- 15851753
TI  - Hirayama disease associated with a severe rhythmic movement disorder involving
      neck flexions.

PMID- 15851755
TI  - Reversal of warfarin-induced anticoagulation with factor VIIa prior to rt-PA in
      acute stroke.

PMID- 15851754
TI  - A 35-year-old woman with uterine fibroids and multiple embolic strokes.

PMID- 15851756
TI  - Severe anaphylactic reaction to glatiramer acetate with specific IgE.

PMID- 15851757
TI  - The effect of entacapone on homocysteine levels in Parkinson disease.

PMID- 15851758
TI  - Personal history: the pipes of pan.

PMID- 15851759
TI  - Lower phenytoin serum levels in persons switched from brand to generic phenytoin.

PMID- 15851760
TI  - Vascular neurology: a new neurologic subspecialty.

PMID- 15851761
TI  - Neurocysticercosis in the United States: review of an important emerging
      infection.

PMID- 15851762
TI  - Clinically mild encephalitis/encephalopathy with a reversible splenial lesion.

PMID- 15851763
TI  - Pharmacokinetics of 5-azacitidine administered with phenylbutyrate in patients
      with refractory solid tumors or hematologic malignancies.
AB  - PURPOSE: To characterize the pharmacokinetic behavior of 5-azacitidine (5-AC), a
      cytidine nucleoside analog, when given with phenylbutyrate, a histone deaceytlase
      inhibitor. PATIENTS AND METHODS: Pharmacokinetic data were obtained from two
      trials involving patients with solid tumor and hematologic malignancies. 5-AC at
      doses ranging from 10 to 75 mg/m2/d was administered once daily as a subcutaneous
      injection for 5 to 21 days in combination with phenylbutyrate administered as a
      continuous intravenous infusion for varying dose and duration every 28 or 35
      days. Serial plasma samples were collected up to 24 hours after 5-AC
      administration. 5-AC was quantitated using a validated liquid
      chromatograph/tandem mass spectrometry method. RESULTS: 5-AC was rapidly absorbed
      with the mean T(max) occurring at 0.47 hour. Average maximum concentration
      (C(max)) and area under the curve (AUC(0-infinity)) values increased in a dose
      proportionate manner with increasing dose from 10 to 75 mg/m2/d; the mean +/- SD
      C(max) and AUC(0-infinity) at 10 mg/m2/d were 776 +/- 459 nM and 1,355 +/- 1,125
      h*nM, respectively, and at 75 mg/m2/d were 4,871 +/- 1,398 nM and 6,582 +/- 2,560
      h*nM, respectively. Despite a short terminal half-life of 1.5 +/- 2.3 hours,
      inhibition of DNA methyl transferase activity in tumors of patients receiving 5
      AC has been documented. CONCLUSION: 5-AC is rapidly absorbed and eliminated when
      administered subcutaneously. Sufficient 5-AC exposure is achieved to produce
      pharmacodynamic effects in tumors.

PMID- 15851764
TI  - Agreement between self-reported breast cancer treatment and medical records in a
      population-based Breast Cancer Family Registry.
AB  - PURPOSE: Although self-report data on treatment for breast cancer are collected
      in some large epidemiologic studies, their accuracy is unknown. METHODS: As part
      of a population-based Breast Cancer Family Registry, questionnaires on initial
      breast cancer treatment and subsequent recurrence were mailed to Australian women
      diagnosed between 1991 and 1998. These self-report data were validated against
      medical records for 895 women. RESULTS: The median recall period was 3.2 years,
      mean age at diagnosis was 44 years, and 81% of women had early-stage breast
      cancer. Agreement between the two data sources was very high for general
      questions about type of treatment (100%, 99%, 99%, and 94% for surgery,
      radiotherapy, chemotherapy, hormonal therapy, respectively). For more specific
      questions about details of each treatment received, agreement was: for radiation
      therapy, 96% and 99% for radiation to the breast and chest wall, respectively;
      for surgery, 83%, 97%, and 88% for lumpectomy, mastectomy, and lymph node
      dissection, respectively; for hormonal therapy, 94% for tamoxifen; and for
      chemotherapy, range between 76% and 93%. There was 97% agreement about whether
      there had been a recurrence, and agreement about the location of recurrence was
      at least 90% for all sites. Agreement regarding stage at diagnosis was 62%, with
      discrepancies mostly due to women with locoregional disease incorrectly reporting
      distant spread. CONCLUSION: This self-report questionnaire can be used to collect
      accurate data on broad categories of initial breast cancer treatment and
      recurrence, and even for more detailed information on specifics of treatment and
      site of recurrence.

PMID- 15851765
TI  - Protein expression of a triad of frequently methylated genes, p73, p57Kip2, and
      p15, has prognostic value in adult acute lymphocytic leukemia independently of
      its methylation status.
AB  - PURPOSE: To study the relationship between protein expression and DNA methylation
      of a triad of cell-cycle regulatory genes known to be frequently methylated in
      adult acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: Protein expression
      of p73, p15, and p57Kip2 was analyzed by immunohistochemistry using a tissue
      microarray (TMA) platform. The TMA was constructed using pretreatment bone marrow
      biopsy specimens from 64 adult patients with ALL. Protein expression was then
      correlated with DNA methylation and relevant clinical biologic characteristics.
      RESULTS: p73 protein expression was observed in 19 (30%) patients, cytoplasmic
      p15 in 19 (31%), and p57 in 40 (70%). Three patients (5%) had expression of all
      three proteins, 16 (29%) of two proteins, 31 (55%) of one protein, and six (11%)
      of zero proteins. An inverse association was observed between p73 DNA methylation
      and protein expression (P = .003). This effect was not observed for either p15 or
      p57Kip2. Expression of any of the proteins studied was not associated with any
      distinct biologic characteristic. By multivariate analysis, expression of
      p57Kip2, cytoplasmic p15, or a combination of p57Kip2 with either p15 or p73 was
      associated with a better overall survival (P < .001, .04, and .03 respectively).
      CONCLUSION: Expression of a triad of cell cycle regulatory proteins that includes
      p73, p15, and p57Kip2 has prognostic value in adult patients with ALL
      independently of the methylation status of each gene.

PMID- 15851766
TI  - Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in
      patients with advanced and refractory solid tumors or lymphoma.
AB  - PURPOSE: The objective of this study was to define the maximum-tolerated dose
      (MTD), the recommended phase II dose, the dose-limiting toxicity, and determine
      the pharmacokinetic (PK) and pharmacodynamic profiles of MS-275. PATIENTS AND
      METHODS: Patients with advanced solid tumors or lymphoma were treated with MS-275
      orally initially on a once daily x 28 every 6 weeks (daily) and later on once
      every-14-days (q14-day) schedules. The starting dose was 2 mg/m2 and the dose was
      escalated in three- to six-patient cohorts based on toxicity assessments.
      RESULTS: With the daily schedule, the MTD was exceeded at the first dose level.
      Preliminary PK analysis suggested the half-life of MS-275 in humans was 39 to 80
      hours, substantially longer than predicted by preclinical studies. With the q14
      day schedule, 28 patients were treated. The MTD was 10 mg/m2 and dose-limiting
      toxicities were nausea, vomiting, anorexia, and fatigue. Exposure to MS-275 was
      dose dependent, suggesting linear PK. Increased histone H3 acetylation in
      peripheral-blood mononuclear-cells was apparent at all dose levels by
      immunofluorescence analysis. Ten of 29 patients remained on treatment for > or =
      3 months. CONCLUSION: The MS-275 oral formulation on the daily schedule was
      intolerable at a dose and schedule explored. The q14-day schedule is reasonably
      well tolerated. Histone deacetylase inhibition was observed in peripheral-blood
      mononuclear-cells. Based on PK data from the q14-day schedule, a more frequent
      dosing schedule, weekly x 4, repeated every 6 weeks is presently being evaluated.

PMID- 15851767
TI  - The cost-quality trade-off: need for data quality standards for studies that
      impact clinical practice and health policy.

PMID- 15851769
TI  - Defining higher order dimensions of self-reported health: further evidence for a
      two-dimensional structure.
AB  - We illustrate a method for understanding the extent to which a pool of fairly
      diverse health status questions can be examined for their dimensionality, by
      first fitting the data to a unidimensional measurement model, then examining item
      fit and residual factor analysis to determine the pattern of deviations from
      unidimensionality. We simultaneously administered five questionnaires to 1,714
      people with cancer and HIV disease and combined all responses into one analysis.
      Item responses were cocalibrated onto one presumed underlying construct, often
      referred to as health-related quality of life (HRQOL). To identify significant,
      higher order substructures in the data, we then conducted a factor analysis of
      the data residuals, revealing two definable higher order dimensions: physical
      well-being and mental well-being. These results agree with other research and
      provide direction for further studies defining these dimensions within an item
      response theory (IRT) tradition.

PMID- 15851770
TI  - Data pooling and analysis to build a preliminary item bank: an example using
      bowel function in prostate cancer.
AB  - Assessing bowel function (BF) in prostate cancer can help determine therapeutic
      trade-offs. We determined the components of BF commonly assessed in prostate
      cancer studies as an initial step in creating an item bank for clinical and
      research application. We analyzed six archived data sets representing 4,246 men
      with prostate cancer. Thirty-one items from validated instruments were available
      for analysis. Items were classified into domains (diarrhea, rectal urgency, pain,
      bleeding, bother/distress, and other) then subjected to conventional psychometric
      and item response theory (IRT) analyses. Items fit the IRT model if the ratio
      between observed and expected item variance was between 0.60 and 1.40. Four of 31
      items had inadequate fit in at least one analysis. Poorly fitting items included
      bleeding (2), rectal urgency (1), and bother/distress (1). A fifth item assessing
      hemorrhoids was poorly correlated with other items. Our analyses supported four
      related components of BF: diarrhea, rectal urgency, pain, and bother/distress.

PMID- 15851771
TI  - Evaluating the statistical significance of health-related quality-of-life change
      in individual patients.
AB  - Assessing individual change is feasible and potentially useful in clinical
      practice. This article provides an overview of the evaluation of statistically
      significant change in health-related quality of life (HRQOL) for individual
      patients. We review the standard error of measurement, standard error of
      prediction, and reliable change indices using a sample of 54 patients receiving
      care at the UCLA Center for East-West Medicine. The largest amount of change
      necessary for statistical significance was found for the reliable change index
      and the smallest change was needed for the standard error of measurement. The
      amount of change required for statistical significance was intermediate for the
      standard error of prediction. The median kappa for classifying change (declined,
      stayed the same, improved) by different indices was .82, indicating a high level
      of agreement. Future research is needed to determine if one index is most
      appropriate for evaluating the significance of individual change.

PMID- 15851772
TI  - Combining distribution- and anchor-based approaches to determine minimally
      important differences: the FACIT experience.
AB  - Health-related quality of life (HRQOL) is an important endpoint in cancer
      clinical trials and in cancer treatment in general; however, the meaningfulness
      of HRQOL scores may not be apparent to clinicians or researchers. Minimally
      important differences (MIDs) can enhance the interpretability of HRQOL scores by
      identifying differences likely to be meaningful to patients and clinicians. This
      article's objective is to describe and provide examples of approaches we have
      used to identify MIDs for instruments in the Functional Assessment of Chronic
      Illness Therapy (FACIT) measurement system. Distribution- and anchor-based
      approaches are described and illustrated. We also discuss the importance of
      assessing the appropriateness of anchors, and we provide suggestions for
      combining results into a single range of plausible MIDs. MIDs for FACIT
      instruments established to date are summarized, and general guidelines that can
      be used to estimate MIDs for other FACIT instruments are provided. Applications
      of MIDs in research are illustrated.

PMID- 15851773
TI  - General population and cancer patient norms for the Functional Assessment of
      Cancer Therapy-General (FACT-G).
AB  - Given the number of new cancer cases diagnosed each year and the increases in
      survival rates, the importance of having a clinically useful health-related
      quality of life (HRQOL) instrument has increased. The Functional Assessment of
      Cancer Therapy-General (FACT-G) is one such instrument that has been used
      worldwide to assess HRQOL. Previously, the use of the FACT-G had been limited
      because of a lack of published normative data. Normative data are useful for
      consumers to place their results in an appropriate context by comparing their
      scores of individuals or group of individuals to a reference group. Here, we
      present normative data for the FACT-G for two reference groups: (a) a sample of
      the general U.S. adult population and (b) a large, heterogeneous sample of adult
      patients with cancer. In addition, we demonstrate various uses of the normative
      data.

PMID- 15851774
TI  - A comprehensive method for the translation and cross-cultural validation of
      health status questionnaires.
AB  - The FACIT (Functional Assessment of Chronic Illness Therapy) translation
      methodology has been in use for nearly 10 years and, during the course of that
      time, has emphasized a universal translation approach that includes multicountry
      review, the use of qualitative and quantitative methods in testing, and the
      exploration of new methods such as differential item functioning (DIF) analysis
      using item response theory to evaluate item equivalence. The FACIT translation
      methodology aims to establish equivalence of meaning and measurement between
      different country versions through the use of the decentered model of translation
      and advanced statistical methods.

PMID- 15851775
TI  - Cross-cultural evaluation of health status using item response theory: FACT-B
      comparisons between Austrian and U.S. patients with breast cancer.
AB  - To make meaningful cross-cultural comparisons of health-related quality of life
      (HRQOL) or to pool international research data, it is essential to create
      culturally unbiased measures that detect clinically important differences between
      patients. We evaluated the measurement properties of the Functional Assessment of
      Cancer Therapy-Breast (FACT-B) in 111 Austrian and 144 U.S. patients with breast
      cancer using item response theory (IRT) methods. A small number of items were
      identified as displaying statistically significant differential item functioning
      (DIF), suggesting possible measurement bias. The majority of the items functioned
      similarly between the two cultural groups. U.S. patients reported lower (worse)
      physical function and well-being compared with Austrian patients, higher (better)
      social/family well-being and similar emotional well-being, before and after
      adjustment for DIF. IRT and related measurement models provide useful methods for
      assessing cross-cultural equivalence and determining which items can be pooled
      across languages before analyzing HRQOL data. Determination of clinically
      significant cross-cultural differences will require additional investigation.

PMID- 15851776
TI  - Thinking outside the box.

PMID- 15851777
TI  - Muscle injuries: biology and treatment.
AB  - Muscle injuries are one of the most common traumas occurring in sports. Despite
      their clinical importance, few clinical studies exist on the treatment of these
      traumas. Thus, the current treatment principles of muscle injuries have either
      been derived from experimental studies or been tested only empirically. Although
      nonoperative treatment results in good functional outcomes in the majority of
      athletes with muscle injuries, the consequences of failed treatment can be very
      dramatic, possibly postponing an athlete's return to sports for weeks or even
      months. Moreover, the recognition of some basic principles of skeletal muscle
      regeneration and healing processes can considerably help in both avoiding the
      imminent dangers and accelerating the return to competition. Accordingly, in this
      review, the authors have summarized the prevailing understanding on the biology
      of muscle regeneration. Furthermore, they have reviewed the existing data on the
      different treatment modalities (such as medication, therapeutic ultrasound,
      physical therapy) thought to influence the healing of injured skeletal muscle. In
      the end, they extend these findings to clinical practice in an attempt to propose
      an evidence-based approach for the diagnosis and optimal treatment of skeletal
      muscle injuries.

PMID- 15851778
TI  - "Subcellular proteomics" of neuromelanin granules isolated from the human brain.
AB  - "Subcellular proteomics" is currently the most effective approach to characterize
      subcellular compartments. Based on the powerful combination of subcellular
      fractionation and protein identification by LC-MS/MS we were able for the first
      time to 1) isolate intact neuromelanin granules from the human brain and 2)
      establish the first protein profile of these granules. This compartment
      containing neuromelanin (NM) is primarily located in the primate's substantia
      nigra, one of the main brain regions that severely degenerates in Parkinson
      disease. We used mechanic tissue disaggregation, discontinuous sucrose gradient
      centrifugation, cell disruption, and organelle separation to isolate NM granules
      from human substantia nigra. Using transmission electron microscopy we
      demonstrated that the morphological characteristics of the isolated NM granules
      are similar to those described in human brain tissue. Fundamentally we found
      numerous proteins definitely demonstrating a close relationship of NM-containing
      granules with lysosomes or lysosome-related organelles originating from the
      endosome-lysosome lineage. Intriguingly we further revealed the presence of
      endoplasmic reticulum-derived chaperones, especially the transmembrane protein
      calnexin, which recently has been located in lysosome-related melanosomes and has
      been suggested to be a melanogenic chaperone.

PMID- 15851780
TI  - Regarding "recommendations for zoledronic acid treatment of patients with bone
      metastases".

PMID- 15851781
TI  - The issue of renal safety of zoledronic acid from a nephrologist's point of view.

PMID- 15851782
TI  - "Safety and convenience of a 15-minute infusion of zoledronic acid": not so safe.

PMID- 15851784
TI  - Safety and compliance of intravenous and oral dosing regimens.

PMID- 15851786
TI  - Bisphosphonate safety and tolerability.

PMID- 15851790
TI  - Adjuvant therapy in stage II colon cancer: current approaches.

PMID- 15851788
TI  - New combinations in metastatic colorectal cancer: what are our expectations?

PMID- 15851791
TI  - Stage II colorectal cancer: to treat or not to treat.

PMID- 15851792
TI  - Which patients with stage III non-small cell lung cancer should undergo surgical
      resection?
AB  - The treatment of patients with stage III NSCLC remains controversial. Stage III
      NSCLC comprises a fairly heterogeneous group of tumors, and furthermore only
      sparse data from randomized clinical trials exist to guide therapy decisions.
      This review article proposes a management algorithm for patients with stage III
      NSCLC that is based upon the currently available data on surgical therapy,
      chemotherapy, and radiation therapy. By necessity, given the paucity of strong
      data, a good deal of opinion is offered. The choice to proceed with aggressive,
      combined modality treatment is presented in light of extent of local disease as
      well as patient performance status.

PMID- 15851793
TI  - HER1/EGFR inhibitor-associated rash: future directions for management and
      investigation outcomes from the HER1/EGFR inhibitor rash management forum.
AB  - Skin rash associated with HER1/epidermal growth factor receptor (EGFR) inhibitors
      is common. The lack of clinical and patient guidance for this often chronic and
      sometimes distressing side effect makes rash management and etiology
      investigation high priorities. To address this, oncologists and dermatologists
      with experience with HER1/EGFR inhibitors attended the HER1/EGFR Inhibitor Rash
      Management Forum. Recommendations include continued analysis of the correlation
      between rash and clinical outcome and improving the accuracy and reproducibility
      of terminology and grading systems. Because acne vulgaris has a unique pathology,
      and the pathology and etiology of rash are unclear yet distinct from acne
      vulgaris, using such terms as acne, acne-like, or acneiform should be avoided.
      Until there is a specific dermatological definition, rash is best described using
      phenotypic terms for its appearance and location. It is currently unknown which
      agents are best for treating rash. Clinical trials of rash treatments are
      urgently required, and suggestions for agents to consider are made based on
      current knowledge. The effect of dose reduction or interruption on rash should
      also be investigated. Secondarily infected rash may be more frequent than has
      been previously recognized, and some investigators favor empiric use of an oral
      antibiotic if this appears to be the case. Suggestions for patients include
      makeup to camouflage the rash and an emollient to prevent and alleviate skin
      dryness. The increasing use of HER1/EGFR-targeted agents makes managing rash
      important. We hope the outcomes from this Forum provide background for future
      studies.

PMID- 15851794
TI  - Effect of patient exclusion criteria on the efficacy of erythropoiesis
      stimulating agents in patients with cancer-related anemia.
AB  - Comparison of the efficacies of erythropoiesis-stimulating agents (ESAs) between
      different clinical trials is becoming increasingly common, although differences
      in study design and populations evaluated can have a considerable effect on
      results. A comparison of two seemingly similar trials of ESAs, one of epoetin
      alfa and the other of epoetin beta, showed that only 27% of the 115 patients with
      hematologic malignancies who received epoetin alfa in the epoetin alfa trial met
      the inclusion criteria for the epoetin beta trial. The mean hemoglobin increase
      from baseline to week 16 of epoetin alfa therapy in the patients who met these
      inclusion criteria was 3.3 g/dl. This is substantially higher than the mean
      hemoglobin increase of 2.2 g/dl from baseline to week 16 of epoetin alfa therapy
      in the patients who did not meet the epoetin beta study inclusion criteria. These
      results demonstrate the considerable effects that exclusion criteria can have on
      trial results and highlight the value of scrutinizing the study design details of
      clinical trials before comparing outcome data between trials.

PMID- 15851795
TI  - The molecular perspective: double-stranded DNA breaks.

PMID- 15851796
TI  - More than half the women with a history of psychosis have a psychiatric episode
      in the first year after childbirth.

PMID- 15851797
TI  - Specialised care for early psychosis may reduce number of readmissions.

PMID- 15851798
TI  - Review: in people with bipolar disorder, short term antidepressants improve
      clinical response, although tricyclics risk inducing mania.

PMID- 15851799
TI  - Fluoxetine improves minor depressive disorders.

PMID- 15851800
TI  - Continuing fluoxetine treatment may delay relapse in children and adolescents
      with major depressive disorder.

PMID- 15851802
TI  - Minimal contact psychotherapy reduces the risk of major depression in people with
      subthreshold depression.

PMID- 15851801
TI  - Cognitive behaviour therapy reduces long term risk of relapse in recurrent major
      depressive disorder.

PMID- 15851803
TI  - Individualised treatment improves depression in people with depression and
      diabetes.

PMID- 15851804
TI  - Rivastigmine modestly improves dementia associated with Parkinson's disease, but
      has important adverse effects.

PMID- 15851805
TI  - Mirtazapine plus citalopram has short term but not longer term benefits over
      citalopram alone for the symptoms of obsessive compulsive disorder.

PMID- 15851806
TI  - Paroxetine improves social anxiety disorder in children and adolescents.

PMID- 15851807
TI  - Review: self-help interventions improve anxiety and mood disorders.

PMID- 15851808
TI  - Review: hippocampal volume is reduced in people with unipolar depression.

PMID- 15851809
TI  - Risk of dementia in people with depressive and bipolar disorders increases with
      increasing number of prior affective episodes.

PMID- 15851810
TI  - Subjective memory deterioration in elderly people is associated with future
      dementia.

PMID- 15851811
TI  - Suicidality in pre-adolescence and early adulthood is associated with
      psychosocial and psychiatric problems in young adulthood.

PMID- 15851812
TI  - Relocation puts elderly nursing home residents at risk of stress, although the
      stress is short lived.

PMID- 15851813
TI  - Axis I disorders are common in people with severe borderline personality
      disorder, but decrease with time.

PMID- 15851814
TI  - Axis II comorbidities are less common in people with borderline personality
      disorder who are in remission.

PMID- 15851815
TI  - Rapid cycling is equivalently prevalent in bipolar I and bipolar II disorder, and
      is associated with female gender and greater severity of illness.

PMID- 15851816
TI  - Study estimates incidence of suicidal ideation and suggests factors that put
      people at risk.

PMID- 15851817
TI  - Lifetime alcohol abstainers and moderate drinkers have a lower lifetime
      prevalence of mood and anxiety disorders than problem drinkers.

PMID- 15851818
TI  - Long term antipsychotic polypharmacy is common among Medicaid recipients with
      schizophrenia.

PMID- 15851819
TI  - Boys in late adolescence have a low rate of use of mental health services.

PMID- 15851820
TI  - Are estrogens protective or risk factors in brain injury and neurodegeneration?
      Reevaluation after the Women's health initiative.
AB  - Estrogens are essential for normal reproductive function. In addition, they exert
      important, complex, and diverse nonreproductive actions on multiple tissues.
      Although accumulating evidence from basic science studies using animal models
      suggests that estradiol plays a critical neuroprotective role against multiple
      types of neurodegenerative diseases and injuries, recent clinical studies have
      reported either inconclusive or untoward effects of hormone therapy on the brain.
      We focus herein on the work that we have done during the past 6 yr that strongly
      suggests that low levels of estradiol therapy exert dramatic protective actions
      in the adult injured brain. Our results reveal that 17beta-estradiol slows the
      progression of this injury and diminishes the extent of cell death by suppressing
      apoptotic cell death pathways and enhancing expression of genes that optimize
      cell survival. Furthermore, we have found that estrogen receptors play a pivotal
      functional role in neuroprotection. Together, these results carry broad
      implications for the selective targeting of estrogen receptors in the treatment
      of neurodegenerative conditions resulting from disease or injury, particularly
      for aging, postmenopausal women.

PMID- 15851821
TI  - The effects of health and environment on exercise-class participation in older,
      urban women.
AB  - This research investigated the effects of health and environmental factors on the
      dropout and intermittent nonattendance of an exercise program designed
      specifically for older, female, primary-care patients living in the inner city.
      Class-attendance records (n = 21,538) from a cohort 110 women were analyzed.
      Women who dropped out early had poorer perceived health and were more likely to
      report pain as an exercise barrier at baseline. Those who lived in a census tract
      where a larger percentage of workers walk to work were less likely to drop out
      early. Intermittent nonattendance was associated with adverse weather conditions
      including heat index above 90 degrees F, wind-chill index below 20 degrees F,
      overcast sky, and snow. Better attendance was associated with greater atmospheric
      pressure, as well as lower number of sunlight hours per day. This research
      highlights the need to better understand environmental barriers when promoting
      physical activities in older women.

PMID- 15851822
TI  - The effect of 6 months training on leg power, balance, and functional mobility of
      independently living adults over 70 years old.
AB  - Where strength training has been used in conjunction with functional-task
      training in older people, not only have there been improvements in leg strength
      but also improved function has been measured (e.g., Skelton & McLaughlin, 1996).
      Many studies use participants from care homes rather than community dwellers. We
      investigated changes in leg power, balance, and functional mobility in community
      dwelling sedentary men and women over 70 years of age (n = 6 for training group
      [TR]; n = 10 for control group [CN]). Progressive training took place over 24
      weeks using seated and nonseated exercise. For TR, leg power increased 40%, from
      108 +/- 40 to 141 +/- 53 W (p < .01); dynamic balance increased 48%, from 22.3 +/
      7.9 to 33.1 +/- 6.1 cm (p < .01; functional reach); and functional mobility
      increased 12%, from 7.46 +/- 1.32 to 6.54 +/- 1.41 s (p < .05; timed walk). CN
      showed no significant change. In conclusion, a community-based exercise program
      led to large improvements in leg-extensor power, dynamic balance, and functional
      mobility.

PMID- 15851823
TI  - Leg-extension strength and chair-rise performance in elderly women with
      Parkinson's disease.
AB  - The lower extremity performance in elderly female patients with mild to moderate
      Parkinson's disease (PD; n = 12) and controls (n = 16) was compared. Isometric
      dynamometry and force-plate measurements were used. PD patients had lower (p <
      .05) bilateral (BL) maximal isometric leg-extension force (MF), BL isometric MF
      relative to body mass, and maximal rate of isometric force development than
      control participants. BL strength deficit was greater (p < .05) in PD patients
      than in controls. A significantly longer chair-rise time and lower maximal rate
      of vertical-ground-reaction-force development while rising from a chair was found
      in PD patients than in controls. These findings suggest that elderly women with
      PD have lowered voluntary isometric force-generation capacity of the leg-extensor
      muscles. Reduced BL leg-extension strength might contribute to the difficulty of
      individuals with PD to rise from a chair.

PMID- 15851824
TI  - Reliability of isokinetic and isometric knee-extensor force in older women.
AB  - Because of the need for efficient, consistent strength measurements, the test
      retest reliability of concentric, isometric, and eccentric strength; concentric
      work; and concentric power was determined in older women without a
      familiarization session. The reliability of measures derived from a single peak
      score were compared with those derived from an averaged score. On 2 occasions 25
      older women with a mean age of 72 +/- 6 years performed 3 submaximal knee
      extensions and 5 maximal contractions on an isokinetic dynamometer at 90
      degrees/s (CON), 0 degrees/s, and -90 degrees/s on both lower limbs. Statistical
      analyses for peak and averaged values (best 3 contractions of 5) exhibited good
      relative reliability (ICCs > .88), except for CON power. Typical error as a
      coefficient of variation and ratio limits of agreement for peak and averaged
      score values were larger than desired, with CON power scores demonstrating
      unacceptable error ranges. Although relative reliability of this 1-session
      assessment protocol was acceptable, further research is needed to determine
      whether additional practice trials could enhance absolute reliability.

PMID- 15851825
TI  - Effects of multicomponent training on functional fitness in older adults.
AB  - The purpose of this study was to evaluate the effects of a 9-week supervised
      multicomponent exercise program on functional fitness and body composition in
      independent older adults. Forty-two adults age 60-86 years were randomly assigned
      to an exercise or a control group and were evaluated before and after training.
      The training program consisted of 3 sessions of walking, strengthening, and
      flexibility exercises per week. The multicomponent training program resulted in
      significant (p < .005) improvements on the chair stand, arm curl, 6-min walk, and
      up-and-go tests. The findings of this study indicate that a 9-week training
      program increased upper and lower body strength, aerobic endurance, and
      agility/dynamic balance in older adults. The most affected components of
      functional fitness were lower body strength and aerobic endurance. There was no
      effect of the 9-week training on body composition.

PMID- 15851826
TI  - Physical activity and hormone-replacement therapy: interactive effects on
      cognition?
AB  - The purpose of this study was to examine the interactive effects of hormone
      replacement therapy (HRT) and physical activity (PA) on the cognitive performance
      of older women. Postmenopausal women (n = 101) were recruited to complete a PA
      questionnaire, provide demographic information, and perform the digit-symbol
      substitution task (DSST) and the trail-making tests (TMT). Regression analyses
      were conducted for participants with complete data for each cognitive test (DSST
      n = 62; TMT n = 69). For both tasks, results indicated that PA and education were
      positively related and age was negatively related to cognitive performance. The
      interaction of HRT with PA did not add to the predicted variance of either
      measure of cognitive performance. This was true even after limiting the HRT users
      to women using unopposed estrogen. It is concluded that the beneficial
      relationship between PA and these two measures of cognitive performance in
      postmenopausal women exists irrespective of HRT use.

PMID- 15851827
TI  - Investigation on liver function among population in high background of rare earth
      area in South China.
AB  - The health effects of long-term ingestion of rare earth elements (REEs) on the
      villagers living in high-REE-background areas in South Jangxi Province, China
      were studied. Major health complaints from the REE area population included
      indigestion, diarrhea, abdominal distension, anorexia, weakness, and fatigue,
      especially after high-fat or high-protein intake. Liver function tests were
      conducted for adult villagers. Among them, 45 live in a heavy rare earth (HREE)
      area, 62 in a light rare earth (LREE) area, and 49 in the control area. Test
      results showed that serum total protein and globulin from both HREE and LREE
      areas, as well as albumin from the LREE area, were significantly lower (p < 0.01 
      0.01) compared to the results from the control area, whereas albumin from the
      HREE area showed no significant variance (p > 0.05). The chi-square test showed
      that Serum-glutamic pyruvic transaminase (SGPT) in both areas were not
      significant (p > 0.05), whereas the IgM in the HREE area was significantly
      elevated. It is our conclusion that long-term ingestion of REE affected
      activities of some digestive enzymes, causing malabsorption and indigestion, and
      might further lead to a low-protein effect for the villagers in the LREE area.
      However, the damage to the liver was rather mild. The elevation of IgM was
      probably the result of stimulation induced by the formation of a large amount of
      granules as a result of direct binding of REEs to globulin or albumin
      (combination of REEs with globulin or albumin).

PMID- 15851828
TI  - Selenium status of idiopathic infertile Nigerian males.
AB  - Selenium concentration in the sera and seminal plasma of 60 infertile males (40
      oligospermia and 20 azoospermia) and 40 males with proven evidence of fertility
      (normospermia; control group) were estimated using atomic absorption
      spectrophotometry. Results were correlated with spermatogram and hormonal levels
      in order to determine their relationship and significance in male infertility.
      The mean serum concentrations of selenium was found to be significantly increased
      in oligospermic compared to azoospermic subjects and controls (p < 0.01), whereas
      the seminal plasma level was significantly higher in azoospermic compared to
      oligospermic subjects and controls (p < 0.001). Thus, the ratio of serum selenium
      to seminal plasma selenium was 1: 1 in controls, 4: 1 in oligospermia, and 1: 2
      in azoospermic subject.A significant inverse correlation was observed between
      serum selenium level and sperm count (p < 0.01). Similarly, seminal plasma
      selenium correlated with spermatozoa motility, viability, and morphology. Serum
      selenium level shows positive correlation with the serum testosterone level (p <
      0.01). In conclusion, there appears to be a physiological balance in the
      distribution of selenium in serum and seminal plasma compartment of control
      males. A disturbance in this balance has a significant influence on
      spermatogenesis. Selenium appears to have a positive influence on Leydig cells,
      thus influencing the secretion of testosterone.

PMID- 15851829
TI  - Effects of ascorbic acid on cadmium-induced oxidative stress and performance of
      broilers.
AB  - The effects of cadmium on performance, antioxidant defense system, liver and
      kidney functions, and cadmium accumulation in selected tissues of broiler
      chickens were studied. Whether the possible adverse effects of cadmium would
      reverse with the antioxidant ascorbic acid was also investigated. Hence, 4
      treatment groups (3 replicates of 10 chicks each) were designed in the study:
      control, ascorbic acid, cadmium, and cadmium plus ascorbic acid. Cadmium was
      given via the drinking water at a concentration of 25 mg/L for 6 wk. Ascorbic
      acid was added to the basal diet at 200 mg/kg either alone or with cadmium.
      Cadmium decreased the body weight (BW), body weight gain (BWG), and feed
      efficiency (FE) significantly at the end of the experiment, whereas its effect on
      feed consumption (FC) was not significant. Cadmium increased the plasma
      malondialdehyde (MDA) level as an indicator of lipid peroxidation and lowered the
      activity of blood superoxide dismutase (SOD). Liver function enzymes, aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase
      (LDH), and gamma glutamyl transferase (GGT) activities were not changed by
      cadmium. Cadmium ingestion did not alter serum creatinine levels. Although the
      serum cadmium level was not elevated, cadmium mainly accumulated in the kidneys,
      liver, pancreas, and muscle. Ascorbic acid supplementation resulted in a
      reduction of MDA level previously increased by cadmium and a restoration in SOD
      activity. However, ascorbic acid did not ameliorate the growth inhibitory effect
      of cadmium nor did it prevent accumulation of cadmium in analyzed tissues. These
      data indicate that oxidative stress, induced by cadmium, plays a role in
      decreasing the performance of broilers and that dietary supplementation by
      ascorbic acid might be useful in reversing the lipid peroxidation induced by
      cadmium and partly alleviating the adverse effect of cadmium on performance of
      broilers.

PMID- 15851830
TI  - Accumulation and distribution of samarium-153 in rat brain after intraperitoneal
      injection.
AB  - It is well known that rare earth elements (REEs) have come into extensive use in
      a number of fields. As a result, REEs are becoming closely related to human's
      daily life. However, until now, the distributions of REEs in the brain are not
      yet very clear. In this study, Sprague-Dawley male rats were intraperitoneally
      injected with 0.25 mL of (153)SmCl(3) solution (containing 10 microg Sm). The
      brains were perfused with saline to minimize the blood influence. The
      radioactivities of (153)Sm in the five brain regions (hypothalamus, cerebellum,
      hippocampus, corpus striatum, and cerebral cortex) were counted. The results
      suggested that Sm did enter into the brain. Although only about 0.0003% of the
      given dose was accumulated in the brain, Sm seemed to be remain in the brain for
      a long time. The highest amounts and lowest concentrations of (153)Sm were found
      in the cerebral cortex, and the highest concentrations of (153)Sm were found in
      the hypothalamus.

PMID- 15851831
TI  - Effects of zinc deficiency and supplementation on plasma leptin levels in rats.
AB  - The effects of zinc deficiency and supplementation on plasma leptin levels were
      studied in Sprague-Dawley rats. After 6 wk on a zinc-deficient diet containing
      0.65 ppm Zn/g, the mean body weight was significantly lower than that of normal
      or zinc-supplemented rats, which showed no difference among them. The plasma
      leptin and zinc levels were lowest in zinc-deficient animals and highest in those
      that received a normal diet and daily intraperitioneal injections of 3 mg Zn/kg.
      These results indicate that zinc deficiency leads to a significant inhibition in
      plasma leptin levels, whereas zinc supplementation significantly increases plasma
      leptin.

PMID- 15851832
TI  - Effects of zinc deficiency and pinealectomy on cellular immunity in rats infected
      with Toxoplasma gondii.
AB  - The effects of zinc and/or melatonin deficiencies on cellular immunity were
      investigated in rats infected with Toxoplasma gondii. A total of 50 adult male
      Sprague-Dawley rats were divided into 5 groups of 10 rats each. In group I, the
      rats were infected with T. gondii and fed a zinc-deficient diet; in group II, the
      rats were infected and their pineal gland was surgically removed. Group III
      included rats that were infected, pinealectomized, and fed a zinc-deficient diet.
      Group IV consisted of T. gondii-infested rats that received no treatment of any
      kind, and group V were normal controls. After 3 wk of treatment, all rats were
      sacrificed and the percentages of CD3, CD4, and CD8 lymphocytes, zinc, and
      melatonin levels in plasma and the percentage of lymphocyte in blood smears were
      analyzed. The CD3 ratios of groups I-III were significantly lower than those of
      groups IV and V (p<0.01). The CD4 lymphocytes were significantly higher in group
      IV than that in all other groups (p<0.05). In group IV, the CD8 lymphocytes were
      higher than in groups I-III (p<0.01) and those in group V were higher than for
      groups I and III (p<0.01). Lymphocyte incidence in group IV was higher than in
      the other four groups (p<0.01). The plasma zinc and plasma melatonin levels in
      groups I-III were significantly lower than those in the controls (p<0.01, both
      cases). These results suggest that zinc and/or melatonin deficiency have a
      negative influence on cellular immunity in rats with toxoplasmosis.

PMID- 15851833
TI  - Role of metallothionein isoforms in bone formation processes in rat marrow
      mesenchymal stem cells in culture.
AB  - Temporal changes in mRNAs for metallothionein (MT) isoforms in subcultures of rat
      marrow mesenchymal stem cells (MSCs) after treatment with dexamethasone were
      investigated. Both MT-1 and MT-2 mRNA expression in the cultured MSCs with
      dexamethasone showed maximum levels at d 1, whereas ALP and osteocalcin mRNAs
      peaked at d 12. MT-3 mRNA was not detected in the cultured MSCs at any time. The
      expression level of MT-2 mRNA at d 1 was 9.4-fold higher than that of MT-1 mRNA.
      Finally, osteoblast differentiation and mineralization of MSCs at d 14 was
      inhibited by the addition of a common antisense oligonucleotide for both MT-1 and
      MT-2 in the culture medium during the first 4 d. The results suggest that the
      large amounts of MT-2 are produced in the early stage of subculture of MSCs, and
      this might regulate their differentiation.

PMID- 15851834
TI  - Translocation of radionuclides of Co, Zn, Se, Rb, Y, Tc, and Re into organs of
      tomato plant via roots.
AB  - The translocation of the radionuclides of Co, Zn, Se, Rb, Y, Tc, and Re into red
      and green fruits, flesh, seeds, rind, calyxes, flower, leaves, and stems via the
      root of the tomato plant at two different growth stages was studied by a
      multitracer technique. The contents (%/g) of Co, Zn, Se, and Y in the roots were
      the highest among the organs, but only small amounts of them were translocated
      into the aerial parts after 5 d cultivation with a multitracer. In contrast, Rb,
      Tc, and Re showed rapid translocation into the stems and leaves from the root. In
      the plants cultivated for 95 d with a multitracer, Zn, Se, and Rb distributed in
      all of the organs, Co in the organs except for flowers, and Y, Tc, and Re in the
      limited organs. The translocation ratio of the elements for the edible part of
      the plants cultivated for 95 d decreased in the order of Rb>Zn>Co approximately
      Se>Tc approximately Y>Re. The transfer factor of the elements for tomato fruit
      was determined to be in the range of 10(-5)-10(-2). The characteristic
      translocation behavior of the elements gives us fundamental information on the
      assessment of pollutant uptake by the tomato plant.

PMID- 15851835
TI  - Effect of nano-TiO(2) on strength of naturally aged seeds and growth of spinach.
AB  - The effects of nano-TiO(2) (rutile) and non-nano-TiO(2) on the germination and
      growth of naturally aged spinach seeds were studied by measuring the germination
      rate and the germination and vigor indexes of aged spinach seeds. An increase of
      these factors was observed at 0.25-4% nano-TiO(2) treatment. During the growth
      stage, the plant dry weight was increased, as was the chlorophyll formation, the
      ribulosebisphosphate carboxylase/oxygenase activity, and the photosynthetic rate.
      The best results were found at 2.5% nano-TiO(2). The effects of non-nano-TiO(2)
      are not significant. It is shown that the physiological effects are related to
      the nanometer-size particles, but the mechanism by which nano-TiO(2) improves the
      growth of spinach seeds still needs further study.

PMID- 15851836
TI  - Blood viscosity changes in experimentally Trypanosoma cruzi-infected rats.
AB  - Microcirculatory alterations would explain focal lesions found in Chagas'
      cardiomyopathy. Trypanosoma cruzi (T. cruzi) infection induces host blood
      properties modifications and defensive responses capable of producing blood
      hyperviscosity, an ischemic risk factor able to affect microvascular blood flow.
      We studied whole blood viscosity (eta(b)) and plasmatic and cellular factors
      influencing it in rats, 7 and 14 days after experimental infection with T. cruzi.
      Increased plasma viscosity (eta(p)) was found in infected versus control rats and
      it was correlated with high blood parasite levels at 7 days and enhanced gamma
      globulin fraction concentration at 14 days. The hematocrit, mean corpuscular
      volume (MCV) and eta(b) were higher in 14 days infected rats vs. 7 days and
      control animals. Also, electron microscopy observation showed morphological
      changes in red blood cells (RBC) at 7 and 14 days post-infection, with increased
      proportion of echinocyte and stomatocyte shapes transformation. In our rat model
      of Chagas' disease, BPL, increased plasmatic protein concentration, enhanced MCV
      and RBC shapes transformation would determine blood hyperviscosity, cause of
      microvascular blood flow abnormalities.

PMID- 15851837
TI  - Fetal hemorheology in normal pregnancy and severe preeclampsia.
AB  - Hemorheological parameters were determined in 45 pairs of mothers with severe
      preeclampsia and their newborns in comparison with 45 women with uncomplicated
      pregnancies and their newborns. In both groups we investigated red cell
      deformability, the plasma viscosity, the red cell aggregation (during stasis and
      low flow), the macromolecules fibrinogen and factor VIIIR:Ag (VWF), and the blood
      count parameters hemoglobin, hematocrit, white cells, platelets, reticulocytes,
      MCV, MCHC. Cholesterol and triglycerides were correlated to the parameter of red
      cell deformability measured as red cell elongation. We found a significant lower
      plasma viscosity, red cell aggregation, fibrinogen, cholesterol, triglycerides
      and VWF in cord blood with a close association between plasma viscosity and
      fibrinogen (r = 0.56, p = 0.001). The red cell deformability measured as red cell
      elongation was statistically higher in the cord blood compared to the mothers and
      associated with a higher MCV. In contrast the MCHC values remained unchanged.
      Hematocrit and hemoglobin in the cord blood were higher than in the mothers. The
      incidence of fetal hyperviscosity-polycytemia syndrome in women with severe
      preeclampsia was between 4.7% and 4.9%. An elevated red cell aggregation was
      found in 2.8% (stasis) and 4.8% (low flow state), respectively. We conclude that
      in fetal blood the higher hematocrit and the presence of larger red cells do not
      cause impaired fetal hemorheology.

PMID- 15851838
TI  - Fetal and juvenile animal hemorheology.
AB  - The study provides information on the blood fluidity in healthy, juvenile sheep
      and rabbits during growth (n = 18), and shows also data from fetal rabbits and
      cats. In the fetal rabbit (n = 3) and cat (n = 2), whole blood viscosity (WBV;
      LS30, Contraves, Switzerland) and plasma viscosity (PV; OCR-D, Paar, Austria) was
      low (WBV (0.7 s(-1)): rabbit: 3.28/3.00/2.44; cat: 7.87/10.88; WBV (94 s(-1)):
      rabbit: 2.57/2.48/2.39; cat: 2.75/3.73 mPa s) (PV: rabbit: 1.10/1.10/1.05; cat:
      1.27/1.39 mPa s), which was associated with a low plasma protein concentration
      and a low erythrocyte count despite a high erythrocyte volume. After parturition,
      blood viscosity increased in rabbits in parallel with hematocrit, while MCV
      decreased (WBV (0.7 s(-1)): 9.28 (8.07/10.88); WBV (94 s(-1)): 3.67 (3.62/3.82);
      PV: 1.15 (1.15/1.25) mPa s). In contrast, in the sheep, whole blood and plasma
      viscosity decreased after delivery (WBV (0.7 s(-1)): 1.31 (0.94/1.88); WBV (94 s(
      1)): 2.45 (2.43/2.85) PV: 1.24 (1.23/1.29) mPa s). Hematocrit and MCV decreased,
      while erythrocyte count increased under these circumstances. In summary, whole
      blood viscosity was similar among fetal sheep, rabbits, and cats and is
      diminished compared to adult individuals to guarantee an optimal oxygen supply
      during a period of life in which the oxygen maintainance of the child depends on
      the health and the environment of the mother. However, during growth, blood
      viscosity rose in rabbits, while it continuously decreased in the sheep. At an
      unknown time point this fall in blood viscosity in lambs must reverse, since
      adult sheep again show a higher blood viscosity than juvenile lambs at the age of
      2 months.

PMID- 15851839
TI  - Capillary angiogenesis and remodeling induced in rat limb by arteriovenous
      shunting.
AB  - Capillary angiogenesis and remodeling induced by arteriovenous (AV) shunting in
      rat hind limb was investigated by evaluating changes in capillary density and
      diameter in the skeletal muscle subject to retrograde flow and high pressure.
      Wistar rats were used, and an AV anastomosis was created in the hind limb. Two
      weeks after AV shunting, the microvasculature in the limb was visualized by GS
      lectine, and the samples were observed using confocal laser microscopy. The
      capillary density were increased by approximately 150% for small vessels (<13
      microm in diameter) under retrograde flow condition, but no change appeared for
      large vessels (>13 microm in diameter). The capillary diameters were not
      significantly different between control and chronic condition. In conclusion,
      retrograde flow produced by AV shunting increased capillary density but it did
      not change the capillary diameter significantly.

PMID- 15851840
TI  - The effects of Chinese herb Angelica in focal cerebral ischemia injury in the
      rat.
AB  - This experiment was designed to study the therapeutic mechanisms of Angelica on
      the focal cerebral ischemia injury of the rat. The ischemic area was determined
      by TTC stain. And terminal deoxynucleotidyl transferase (TDT) mediated DUTP
      biotin nick end labeling (TUNEL) method was applied to detect neuronal apoptosis.
      The expressions of Bcl-2 and Bax proteins were observed by immunohistochemical
      staining methods. Results show that the treatment with angelica reduced the
      volume of cerebral infarction (p < 0.05), and that the number of neuronal
      apoptosis cells decreased significantly (p < 0.01). Also the expression level of
      Bax protein decreased (p < 0.01). These results suggest that Angelica can reduce
      the number of apoptosis cells by decreasing the expression of Bax protein. This
      is maybe one of the mechanisms of the therapeutic effect of Angelica on focal
      cerebral ischemia injury.

PMID- 15851841
TI  - Attenuation of endothelial dysfunction by exercise training in STZ-induced
      diabetic rats.
AB  - The protective effects of exercise training on the diabetic-induced endothelial
      cell (EC) dysfunction were determined using intravital fluorescent microscopy.
      Male Sprague-Dawley rats were divided into three groups of control (Con),
      diabetes (DM), and diabetes with exercise--training (DM+Ex). Diabetes was induced
      by single intravenous injection of streptozotocin (STZ; 50 mg/kg BW). The
      exercise training protocol consisted of treadmill running, 5 times/week with the
      velocity of 13-15 m/min, 30 min/day periods for 12 and 24 weeks (wks). 24 wks
      after the STZ injection, blood glucose (BG), glycosylated hemoglobin (HbA1C),
      mean arterial blood pressure (MAP) and heart weight (HW) were significantly
      higher in DM rats (p < 0.001). However, DM+Ex rats had reduced the abnormalities
      of MAP (p < 0.01) and HW (p < 0.05) compared with DM rats. Furthermore, there was
      a significant decrease in heart rate (HR) of DM+Ex rats (p < 0.05) relative to
      Con rats. To examine the influence of exercise training on EC dysfunction,
      leukocyte-EC interactions in mesenteric venules and vascular reactivity responses
      to vasodilators in mesenteric arterioles were monitored by using intravital
      fluorescence microscopy. The diabetic state enhanced leukocyte adhesion in
      mesenteric postcapillary venules (p < 0.001). Moreover, an impaired vasodilatory
      response to the EC-dependent vasodilator, acetylcholine (Ach), not to sodium
      nitroprusside (SNP), was found in 12- and 24-wk diabetic rats (p < 0.01). The
      leukocyte adhesion and the impairment of EC-dependent vasodilation to Ach were
      attenuated by exercise training (p < 0.05). In addition, exercise training was
      also shown to have favorable preventive effects on hyperglycemia induced
      oxidative stress, as lower malondialdehyde (MDA) levels were observed from both
      groups of 12 and 24 weeks DM+Ex compared with DM (p < 0.01). In conclusion, our
      findings indicate that the endothelial dysfunction of diabetic rats could be
      characterized by increased leukocyte adhesion and impaired endothelium-dependent
      relaxation. Regular low intensity exercise training could improve both indices of
      endothelial dysfunction through amelioration of diabetic-induced
      oxidant/antioxidant levels. These findings support the notion that regular
      exercise training could be a fundamental form of therapy in preventing diabetic
      cardiovascular complications potentiated by endothelial dysfunction.

PMID- 15851842
TI  - Influence of contrast media (iopromide, ioxaglate, gadolinium-DOTA) on blood
      viscosity, erythrocyte morphology and platelet function.
AB  - The influence of contrast media on blood viscosity, erythrocyte morphology and
      platelet function was studied. In vitro blood was incubated with iopromide
      (Ultravist), ioxaglate (Hexabrix) or gadolinium-DOTA (Dotarem). Plasma viscosity
      and whole blood viscosity were measured and the mean erythrocyte volume and
      morphology were assessed. Platelet aggregation was measured with a PFA-100
      instrument. In an ex vivo study on patients receiving these contrast media the
      same measurements as described above were done. All contrast media increased
      blood viscosity at high shear rate in a dose dependent manner (e.g. with
      ioxaglate: from 4.9+/-0.2 mPa x s to 8.6+/-0.5 mPa x s at 160 mg I/ml), decreased
      low shear viscosity (for ioxaglate: from 44.9+/-2.5 to 27.7+/-4.8 mPa x s),
      increased plasma viscosity (ioxaglate: from 1.2+/-0.1 to 2.8+/-1.3 mPa x s),
      decreased the mean erythrocytic volume (ioxaglate: from 89.7+/-1.4 to 79.7+/-2.0
      fl) and decreased platelet aggregation. Iopromide induced an echinocytic shape
      transformation of erythrocytes. Ex vivo a decreased hematocrit and a
      consecutively decreased whole blood viscosity were found with iopromide and
      ioxaglate. We conclude that contrast media influenced blood rheology,
      erythrocytes and platelet aggregation in vitro and ex vivo.

PMID- 15851843
TI  - Endovascular stent configuration affects intraluminal flow dynamics and in vitro
      endothelialization.
AB  - Neointimal hyperplasia influenced by intravascular hemodynamics is considered
      partly responsible for restenosis after endovascular stenting. To evaluate the
      effect of stent configuration on fluid flow behavior, we visualized flow near
      stents, and measured the proliferation of cultured endothelial cells (ECs). A
      single-coil stent (coil pitch; CP = 2.5, 5, or 10 mm) was inserted into a glass
      tube and perfused at 30-90 ml/min, while the flow pattern was determined by
      particle imaging velocimetry. The reduction of the flow velocity near the wall
      was correlated with the decrease in the coil interval of the stent. In perfusion
      cultures with stents, the proliferation of ECs was influenced by the local flow
      velocity distribution. When a stent with a CP value of 10 mm was used, the
      doubling time of ECs was 30.7 h, while the doubling time was 38.5 h when the CP
      was 5 mm. The doubling time of ECs was shorter at sites upstream of the stent
      wire where the velocity was higher than downstream of the wire. In conclusion, a
      single-coil stent can be used to modify hemodynamic factors, suggesting that
      improved stent design may facilitate rapid endothelialization after stent
      implantation.

PMID- 15851844
TI  - The high frequency properties of brain tissue.
AB  - Computer modeling is becoming increasingly important in the realm of brain
      biomechanics and injury. New computer simulations range from modeling of brain
      surgery, a low frequency, high strain event, to predicting injury as a result of
      an impact to the head, a high frequency event with varying strain magnitudes.
      This range of modeling efforts requires characterization of the tissue over as
      wide a frequency and strain range as possible. Research done to date has
      concentrated on the low frequency properties of the tissue. Complex compression
      and complex shear moduli have been measured at frequencies up to 350 Hz. Impact
      modeling requires use of frequency data at significantly higher frequencies than
      these. The "wave-in-a-tube" ultrasonic method was applied to brain tissue to
      determine mechanical properties at frequencies between 100 kHz and 10 MHz. Of
      these properties, only complex bulk modulus |K*| is fairly invariant (2133 MPa)
      with respect to frequency. Complex shear and complex Young's moduli vary with
      frequency and approach an asymptotic upper limit. Some variation in complex
      Poisson's ratio was also observed.

PMID- 15851845
TI  - Comparison of blood rheological models for physiological flow simulation.
AB  - The present study investigates the flow effects that different blood constitutive
      equations induce when employed in numerical simulations in the framework of
      computational hemodynamics. In accord with experimental studies on the
      rheological behavior of blood, three blood constitutive equations namely the
      Casson, Power-Law and Quemada models were used for simulating the shear flow
      behavior of blood. The case studied is the flow in a channel with a moving part
      of the boundary and was selected because it reproduces the flow phenomena
      occurring in realistic arterial conditions. Flow simulation for every model is
      carried out assuming the same flow rate at the inlet of the channel and different
      Strouhal numbers reflecting different intensities of the boundary movement.
      Results show that the modeling of blood as non-Newtonian fluid has marked
      qualitative and quantitative effects on both the flow field and the wall shear
      stress whereas comparison of the different models shows good agreement between
      the flow effects by the Casson and Quemada models.

PMID- 15851846
TI  - Secondary Alzheimer started by cryptococcal meningitis.

PMID- 15851848
TI  - Differential loss of synaptic proteins in Alzheimer's disease: implications for
      synaptic dysfunction.
AB  - The objective of our research was to determine synaptic protein levels in brain
      specimens from AD subjects and age-matched control subjects. Further, to
      determine whether presynaptic or postsynaptic compartments of neurons are
      preferentially affected in AD patients, we studied 3 presynaptic vesicle proteins
      (synaptotagmin, synaptophysin, and Rab 3A), 2 synaptic membrane proteins (Gap 43
      and synaptobrevin), and 2 postsynaptic proteins (neurogranin and synaptopodin) in
      specimens from AD and age-matched control brains. Two brain regions--the frontal
      and parietal cortices--were assessed for protein levels by immunoblotting
      analysis. We found a loss of both presynaptic vesicle proteins and postsynaptic
      proteins in all brain specimens from AD patients compared to those from age
      matched control subjects. Further, we found that the loss of synaptic proteins
      was more severe in the frontal cortex brain specimens than in the parietal cortex
      brain specimens from the AD subjects compared to those from the control subjects,
      suggesting that the frontal brain may be critical for synaptic function in AD.
      Using immunohistochemistry techniques, we also determined the distribution
      pattern of all synaptic proteins in both the frontal and parietal cortices brain
      specimens from control subjects. Of the 7 synaptic proteins studied, the
      presynaptic proteins synaptophysin and rab 3A and the postsynaptic protein
      synaptopodin were the most down-regulated. Our study suggests that postsynaptic
      proteins and presynaptic proteins are important for synaptic function and may be
      related to cognitive impairments in AD.

PMID- 15851849
TI  - One novel presenilin-1 gene mutation in a Chinese pedigree of familial
      Alzheimer's disease.
AB  - This study is to explore whether there is presenilin 1 (PS1) gene mutation in
      Chinese familial Alzheimer's disease (FAD). There has been no such systemic
      research before in China. Using polymerase chain reaction, single strand
      conformation polymorphism (PCR-SSCP), followed by denaturing high performance
      liquid chromatograph (DHPLC) and DNA sequencing, we analyzed a Chinese family
      with early onset AD. The patients in this family showed a novel missense mutation
      in exon 4 of the PS1 gene (G to T change in codon 97), altering valine to leucine
      acid substitution. Because the change occurred in conserved domains of this gene,
      and is not present in normal controls, this novel mutation is likely to be
      causative of Chinese FAD.

PMID- 15851850
TI  - Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer
      disease.
AB  - Biomarkers to assist in the diagnosis and medical management of Alzheimer disease
      (AD) are a pressing need. We have employed a proteomic approach, microcapillary
      liquid chromatography mass spectrometry of proteins labeled with isotope-coded
      affinity tags (ICAT), to quantify relative changes in the proteome of human
      cerebrospinal fluid (CSF) obtained from the lumbar cistern. Using CSF from well
      characterized AD patients and age-matched controls at 2 different institutions,
      we quantified protein concentration ratios of 42% of the 390 CSF proteins that we
      have identified and found differences > or = 20% in over half of them. We
      confirmed our findings by western blot and validated this approach by quantifying
      relative levels of amyloid precursor protein and cathepsin B in 17 AD patients
      and 16 control individuals. Quantitative proteomics of CSF from AD patients
      compared to age-matched controls, as well as from other neurodegenerative
      diseases, will allow us to generate a roster of proteins that may serve as
      specific biomarker panels for AD and other geriatric dementias.

PMID- 15851851
TI  - N-acteyl cysteine alleviates oxidative damage to central nervous system of ApoE
      deficient mice following folate and vitamin E-deficiency.
AB  - Oxidative stress is an early neurodegenerative insult in Alzheimer's disease
      (AD). Antioxidant mechanisms, including elements of the glutathione (GSH)
      pathway, undergo at least a transient compensatory increase that is apparently
      insufficient due to continued oxidative damage during disease progression. Mice
      deficient in apolipoprotein E, which provide a model for some aspects of AD,
      undergo increased oxidative damage to brain tissue and cognitive decline when
      maintained on a folate-free diet, despite a compensatory increase in glutathione
      synthase transcription and activity as well as increased levels of GSH. Dietary
      supplementation with N-acetyl cysteine (1 g/kg diet), a cell-permeant antioxidant
      and GSH precursor, alleviated oxidative damage and cognitive decline, and
      restored glutathione synthase and GSH levels in ApoE-deficient mice deprived of
      folate to those of normal mice maintained in the presence of folate. These data
      support the administration of antioxidant precursors to buffer oxidative damage
      in neurodegenerative disorders.

PMID- 15851852
TI  - Novel mutations introduced at the beta-site of amyloid beta protein precursor
      enhance the production of amyloid beta peptide by BACE1 in vitro and in cells.
AB  - Abnormal production and accumulation of amyloid-beta peptide (Abeta) plays a
      major role in the pathogenesis of Alzheimer's disease (AD). beta-secretase
      (BACE1) is responsible for the cleavage at thebeta-site in amyloid beta protein
      precursor (AbetaPP/APP) to generate the N-terminus of Abeta. Here we report the
      stepwise identification and characterization of a novel APP-beta-site mutant,
      "NFEV" (APP_NFEV) in vitro and in cells. In vitro, the APP_NFEV exhibits 100-fold
      enhanced cleavage rate relative to the "wild-type" substrate (APPwt) and 10-fold
      increase relative to the Swedish-type mutation variant (APPsw). In cells, it was
      preferably cleaved among 24 APP beta-site mutations tested. More importantly, the
      APP_NFEV mutant failed to generate any detectable Abeta peptides in BACE1-KO
      mouse fibroblast cells. The production of Abeta peptides was restored by co
      transfecting human BACE1, demonstrating that BACE1 is the only enzyme responsible
      for the processing of APP_NFEV in these cells. Analysis of APP_NFEV cleavage
      products secreted in the media revealed that in cells BACE1 cleaves APP_NFEV at
      the position between NF and EV, identical to that observed in vitro. A BACE
      inhibitor blocked the processing of the APP_NFEV beta-site in vitro and in cells.
      Our data indicates that the "NFEV" mutant is not only an enhanced substrate for
      BACE1 in vitro, but also a specific substrate for BACE1 in cells.

PMID- 15851853
TI  - Olfactory involvement in aging and Alzheimer's disease: an autopsy study.
AB  - Olfactory dysfunction and tau pathology in the olfactory bulb increase with the
      severity of Alzheimer's disease. We report data of a postmortem study in the
      aged. 130 autopsy cases (81 female, 49 male, aged 61-102, mean 82.48 +/- 4.35 SD)
      years, underwent a standardized neuropathological assessment with
      immunohistochemical study of tau pathology in the olfactory bulb and nerve and of
      Alzheimer's disease using established criteria including Braak staging. All cases
      of definite Alzheimer's disease (Braak stages 5 and 6) (n = 40) showed large
      numbers of neuropil threads and neurofibrillary tangles, with amyloid deposits in
      32.5% and neuritic plaques in one single case in the olfactory system. Braak
      stage 4 (n = 27) was associated with mild to moderate tau pathology in 85.2%, and
      amyloid plaques in 1.1%, Braak stage 3 (n = 28) with olfactory tau lesions in
      37.0% and amyloid deposits in one single case, Braak stages 3 and 4 with
      olfactory tau lesions in 61.1%. Braak stage 2 (n = 15) showed olfactory tau
      pathology in 31.2%, whereas Braak stages 0 and 1 (n = 15) were all negative. The
      olfactory system tau score showed highly significant correlations with neuritic
      Braak stages in the brain, while both scores showed significant but low
      correlations with age. These data confirm previous studies demonstrating abundant
      tau pathology in the olfactory system in all definite Alzheimer's disease cases,
      in two-thirds of limbic Alzheimer's disease, and in almost one-third of non
      demented elderly persons with Braak stage 2. There are strong correlations
      between tau pathology in the olfactory and limbic systems, both with similar
      increase in severity. Clinical dementia correlated with both Braak and olfactory
      system tau scores. Since the involvement of both systems is associated with a
      high risk of cognitive decline, future studies should validate the sensitivity of
      olfactory mucosa biopsies in the diagnosis of Alzheimer's disease.

PMID- 15851854
TI  - Characterization of the F198S prion protein mutation: enhanced glycosylation and
      defective refolding.
AB  - Prion diseases are associated with the accumulation of a misfolded, protease
      resistant form of the prion protein, PrPres. In humans there are a variety of
      different prion related diseases that are sporadic, inherited, or acquired by
      infection. Gerstmann-Straussler-Sheinker syndrome (GSS) is an inherited prion
      disease in which PrPres accumulates as amorphous aggregates as well as in amyloid
      plaques. GSS has been associated with a variety of point mutations in the prion
      protein: 102, 105, 117, 131, 145, 187, 198, 202, 212, 217, and 232. The F198S
      mutation was discovered in a large Indiana kindred. Previous studies in vitro
      have shown that the 198 mutation results in structural instability of the prion
      protein. In the current study, we demonstrate in a cell model that the F198S
      mutant protein can be folded properly in a cellular context, but is unable to
      refold to a native state after denaturation. Further, the F198S mutation
      significantly affects glycosylation of the mutant protein.

PMID- 15851856
TI  - Which pressure ulcer risk scales are valid and reliable in a pediatric
      population?

PMID- 15851857
TI  - Protection of child human subjects.
AB  - Historical evidence indicates that research in child issues often involved
      institutionalized children, which resulted in the development of federal
      regulations for the protection of child human subjects. The central problem in
      research concerning children is that children lack the legal ability to consent.
      Therefore, federal regulations mandate that for children over 7 parental
      permission and child assent are required. In the assessment of risks and
      benefits, investigators and reviewers should consider children's age, maturity,
      and psychological state. The purpose of this article is to summarize the history
      on research in children and the development of current federal regulations and
      ethical principles. Then it focuses on children's involvement in the research
      participation decision and assesses associated developmental risk factors.

PMID- 15851858
TI  - The 2003 national pediatric pressure ulcer and skin breakdown prevalence survey:
      a multisite study.
AB  - OBJECTIVE: The purpose of this study was to document the prevalence of pressure
      ulcers and other types of skin breakdown in hospitalized children. DESIGN: This
      descriptive study included documentation of findings from chart reviews and
      physical assessments of children. SETTING AND SUBJECTS: Nine children's hospitals
      from throughout the United States participated for a total sample of 1064
      children. Subjects were inpatients in the children's hospitals between the ages
      of neonate to 17 years. INSTRUMENTS: The data collection tools included the
      interrater reliability quiz, the patient data collection form, FAST data
      collection software, the Braden Q Risk Assessment Scale, and the Neonatal/Infant
      Braden Q Risk Assessment Scale. METHODS: Prevalence of pressure ulcers and skin
      breakdown was measured on a predetermined day during an 8-hour period at each
      institution. Eight hospitals required a signed informed consent before study
      participation; 1 hospital's institutional review board waived consent. A physical
      skin assessment was done on each inpatient, and all pressure ulcers found were
      staged according to the National Pressure Ulcer Advisory Panel staging system. A
      chart review was done on all subjects to collect information on patient
      demographics and potential risk factors. The Neonatal/Infant Braden Q Risk
      Assessment was scored for infants younger than 1 year old, and the Braden Q Risk
      Assessment for children 1 year and older. Patient data collection forms were
      completed, and all data were entered into the FAST data collection software at
      the end of the study day. Analyses of data and reports were generated from a
      central site. RESULTS: There were 1,064 children surveyed, with a pressure ulcer
      prevalence of 4.0% and other skin breakdown prevalence of 14.8%. Ninety-two
      percent of the pressure ulcers were partial thickness, Stages I and II. Sixty-six
      percent of the pressure ulcers were facility associated. Locations of pressure
      ulcers were predominately in the head area 31%, seat area 20%, and foot area 19%.
      The 3 most common types of skin breakdown were excoriation/diaper dermatitis,
      skin tear, and IV extravasation. Predominant locations for skin breakdown were
      seat area 35%, foot area 20%, and upper extremities 18%. CONCLUSIONS: The
      prevalence of pressure ulcers was low in the pediatric population studied, but
      skin breakdown prevalence (excluding pressure ulcers) was higher, with 74% of all
      wound types consisting of excoriation/diaper dermatitis, skin tears, and IV
      extravasation sites. Future studies are needed to evaluate prevention and
      treatment options for pressure ulcers and skin breakdown in this population.
      Repeating this multisite study at intervals may be beneficial to continue to
      build and modify the benchmark data.

PMID- 15851859
TI  - Risk factors associated with pressure ulcers in the pediatric intensive care
      unit.
AB  - OBJECTIVE: To identify risk factors that are associated with the development of
      pressure ulcers in children admitted to the pediatric intensive care unit (PICU).
      DESIGN: Case control study with no interventions held in a 30-bed PICU of Texas
      Children's Hospital, Houston. SETTING AND SUBJECTS: The study included 59
      patients who developed pressure ulcers in the PICU and 59 patients who were
      critically ill who did not develop pressure ulcers during the same time period.
      INSTRUMENTS: Risk assessment data collection tool and Braden scale. METHODS: A
      comparison was done to identify risk factors between 2 groups of pediatric
      patients with and without pressure ulcers. A 45-indicator assessment tool was
      used. Physical assessment including staging of pressure ulcers was performed.
      RESULTS: Risk factors associated with pressure ulcers include edema (P = .0016),
      length of stay > 96 hours (P = .001), increasing positive end expiratory pressure
      (P = .002), not turning the patient or use of a specialty bed in the turning mode
      (P = .0001), and weight loss (P < .0001). CONCLUSIONS: The presence of edema,
      increasing length of stay, patients on increasing positive-end expiratory
      pressure, not turning the patient, use of a specialty bed in the turning mode,
      and weight loss are associated with the increased risk of development of pressure
      ulcers in patients in the PICU.

PMID- 15851860
TI  - Case studies of an infant, a toddler, and an adolescent treated with a negative
      pressure wound treatment system.
AB  - Three pediatric case studies (infant, toddler, and adolescent) using negative
      pressure wound treatment system (NPWS) in a children's hospital are described.
      Each child had complex surgical wounds and different goals for the therapy. The
      infant had an ulcerating labial hemangioma surgically removed, and the NPWS was
      used to expedite granulation tissue in preparation for a split-thickness skin
      graft. The critically ill toddler required abdominal fasciotomies for compartment
      syndrome, and the NPWS was applied to reduce interstitial abdominal edema and
      manage the excessive wound drainage. The adolescent initially had surgery to
      correct a pectus excavatum; when the sternal wound became infected and required
      debridement, the NPWS was used to expedite wound healing. The results of the NPWS
      were positive. Although this therapy has been used more commonly in adults, these
      case studies demonstrate its efficacy in several different types of wounds and
      age groups of children. The wound, ostomy, continence nurse should include the
      NPWS in his or her treatment differential as a valuable option for pediatric
      patients.

PMID- 15851861
TI  - A practical guide for the management of pediatric gastrostomy tubes based on 14
      years of experience.
AB  - Children require long-term enteral access for a variety of medical problems.
      Common reasons include cerebral palsy, congenital anomalies, failure to thrive,
      cystic fibrosis, inborn errors of metabolism, and HIV/AIDS. Although this will
      generally be accomplished with a gastrostomy tube, some children will not
      tolerate gastrostomy feedings and will have a jejunostomy placed or have their
      gastrostomy converted to a gastrojejunostomy tube. This article explains 3
      methods of tube placement, discusses styles of gastrostomy tubes and their pros
      and cons, reviews management of tubes, and discusses common problems and their
      solutions.

PMID- 15851862
TI  - Similar gastrostomy peristomal skin irritations in three pediatric patients.

PMID- 15851864
TI  - Structure and function of the gastrointestinal tract in infants and children.
AB  - An understanding of gastrointestinal tract development is essential in
      understanding the pathology and management of common structural anomalies and
      functional disorders in the pediatric population. This article reviews key steps
      in the embryologic development of the gastrointestinal tract and the acquisition
      of fecal continence, with brief explanations of common functional and structural
      disorders.

PMID- 15851866
TI  - Children with chronic continence problems: the challenges for families.
AB  - For families who are raising children with myelomeningocele, bowel and bladder
      incontinence presents unique challenges for everyday life. The Parenting and
      Childhood Chronicity model is used to describe the work of raising a child with a
      chronic condition in 6 areas, including medical care, adapted parenting, dealing
      with the systems, caring for siblings, maintaining relationships, and personal
      coping (keeping yourself going). This article provides an overview of the
      physiologic and developmental challenges inherent in this neural tube defect and
      illustrates the work that is involved in the child's care and the challenges of
      maintaining a balance in family life. Clinical implications are discussed,
      including the setting of appropriate expectations, providing parents with
      accurate information, ensuring that a focus on continence is not at the expense
      of other important aspects of the child's functioning, and supporting parents in
      their interaction with the school system. The medical team, consisting of
      nursing, urology, nephrology, and psychology working together, can be a strong
      support for families.

PMID- 15851867
TI  - Treating nocturnal enuresis in children: review of evidence.
AB  - BACKGROUND: Childhood nocturnal enuresis (bedwetting) affects many families.
      Although it has a high rate of spontaneous remission, bedwetting may bring social
      and emotional stigma, stress, and inconvenience to both the child with enuresis
      and his or her family. DESIGN: Summary of systematic reviews of treatment for
      nocturnal enuresis in children, published in the Cochrane Library, using evidence
      only from randomized and quasi-randomized trials to compare interventions.
      Interventions included behavioral, alarm, and pharmacologic treatments. SETTING
      AND METHODS: Six Cochrane Reviews contributed evidence to this review: simple
      behavioral interventions, alarms, complex behavioral or educational
      interventions, desmopressin, tricyclics and related drugs, and other drugs.
      SUBJECTS: The participants were children (usually up to the age of 16). RESULTS:
      Much of the available evidence was of poor quality, and there were few direct
      comparisons between different types of intervention. Simple behavioral
      Interventions, such as reward systems, are widely used as standard first-line
      treatment, but they require a high level of parental involvement. There is
      currently little evidence to show that these interventions work, but they may be
      worth trying because they have only a few adverse effects. The use of an alarm
      intervention reduced nighttime bed wetting in a majority of children both during
      and after treatment. Overlearning or dry-bed training may reduce the relapse
      rate. Before embarking on alarm treatment, families need to be made aware of both
      the time and the high level of parental involvement necessary to attain success.
      Drug therapy, such as desmopressin and tricyclics, reduced the number of wet
      nights per week compared with placebo but only while the drug was used. Patients
      and their families need to be warned about possible side effects of some of the
      drugs. CONCLUSIONS: Alarms are the most effective treatment for nocturnal
      enuresis in children, but desmopressin may be considered for temporary relief.

PMID- 15851870
TI  - Strategies to reduce cardiac risk in noncardiac surgery: where are we in 2005?

PMID- 15851868
TI  - A multicenter evaluation of absorbent products for children with incontinence and
      disabilities.
AB  - OBJECTIVE: To evaluate all disposable pull-up-style pads (pull-ups) designed for
      children with learning and or physical disabilities and compare these with a
      representative sample of disposable diapers (diapers). DESIGN: A multicenter
      randomized crossover trial where all children evaluated each product. SETTING AND
      CHILDREN: A total of 61 community dwelling children with disabilities were
      recruited from 5 areas throughout the United Kingdom. Families were invited by
      letter to participate through their local clinical nurse specialist for
      continence care. INSTRUMENTS: Instruments used included a range of questionnaires
      (product performance, design performance, and design preference questionnaires)
      and pad weight and leakage diaries. METHODS: The children tested 10 products (5
      pull-ups and 5 diapers) for up to 1 week per product both at home and at school.
      Caregivers (parents and guardians) completed the questionnaires after evaluation
      of individual products and design groups had been completed. They recorded wet
      product weights and scored pad leakage at each pad change. School staff completed
      an abbreviated product performance questionnaire for each product. RESULTS: There
      was little difference in the overall performance of the pull-ups compared with
      the diapers. In the pull-up group, one product performed significantly worse than
      the others for some performance aspects. Pull-ups worked particularly well for
      children able to assist with toileting and pad changes. Diapers were liked for
      ease of changing if the child used calipers, adapted footwear, or trousers.
      Diapers were more popular than pull-ups for night use, when greater absorbency
      was required. Neither design performed differently for school or home use. Most
      caregivers expressed a preference for diapers or pull-ups based on a range of
      individual needs, for example, level of independence in toileting, discreteness
      in pad change, fit, and product appearance. CONCLUSIONS: Diapers and pull-ups
      have different strengths and limitations, and both meet the specific needs of
      individual children. Although pull-ups are more expensive than diapers, their use
      is justified if based on a thorough assessment of individual need.

PMID- 15851871
TI  - Preoperative smoking cessation: how long is long enough?

PMID- 15851872
TI  - Early and delayed myocardial infarction after abdominal aortic surgery.
AB  - BACKGROUND: Although postoperative myocardial infarction (PMI) after vascular
      surgery has been described to be associated with prolonged ischemia, its exact
      pathophysiology remains unclear. METHODS: The authors used intense cardiac
      troponin I (cTnI) surveillance after abdominal aortic surgery in 1,136
      consecutive patients to better evaluate the incidence and timing of PMI (cTnI >
      or = 1.5 ng/ml) or myocardial damage (abnormal cTnI < 1.5 ng/ml). RESULTS:
      Abnormal cTnI concentrations was noted in 163 patients (14%), of which 106 (9%)
      had myocardial damage and 57 (5%) had PMI. In 34 patients (3%), PMI was preceded
      by a prolonged (> 24 h) period of increased cTnI (delayed PMI), and in 21
      patients (2%), the increase in cTnI lasted less than 24 h (early PMI). The mean
      times from end of surgery to PMI were 37 +/- 22 and 74 +/- 39 h in the early PMI
      and delayed PMI groups, respectively (P < 0.001). The mean time between the first
      abnormal cTnI and PMI in the delayed PMI group was 54 +/- 35 h, during which the
      cTnI profiles of the myocardial damage and delayed PMI groups were identical. In
      hospital mortality rates were 24, 21, 7, and 3% for the early PMI, delayed PMI,
      myocardial damage, and normal groups, respectively. CONCLUSIONS: Intense
      postoperative cTnI surveillance revealed two types of PMI according to time of
      appearance and rate of increase in cTnI. The identification of early and delayed
      PMI may be suggestive of different pathophysiologic mechanisms. Abnormal but low
      postoperative cTnI is associated with increased mortality and may lead to delayed
      PMI.

PMID- 15851873
TI  - Determination of the duration of preoperative smoking cessation to improve wound
      healing after head and neck surgery.
AB  - BACKGROUND: Preoperative smoking cessation has been suggested to be effective in
      reducing various postoperative complications. However, the optimal duration of
      preoperative smoking cessation for reducing wound complications is unclear.
      METHODS: One hundred eighty-eight consecutive patients who underwent
      reconstructive head and neck surgery at the authors' institution were included in
      this retrospective study. Information on preoperative smoking habits was obtained
      from the patients' medical records. Smokers were defined as having smoked within
      7 days before surgery. Late, intermediate, and early quitters were defined as
      patients whose duration of abstinence from smoking was 8-21, 22-42, and 43 days
      or longer before the operation, respectively. Patients who required postoperative
      debridement, resuture, or reconstruction of their flap before hospital discharge
      were defined as having had impaired wound healing. RESULTS: The incidences (95%
      confidence intervals) of impaired wound healing among the late, intermediate, and
      early quitters and nonsmokers were 67.6% (52-83%), 55.0% (33-77%), 59.1% (47
      71%), and 47.5% (32-63%), respectively, and the incidence of impaired wound
      healing was significantly lower among the intermediate quitters, early quitters,
      and nonsmokers than among the smokers (85.7% [73-97%]). After controlling for
      sex, age, American Society of Anesthesiologists physical status, operation time,
      history of diabetes mellitus, chemotherapy, radiation therapy, and the type of
      flap, the odds ratios (95% confidence intervals) for development of impaired
      wound healing in the late, intermediate, early quitters, and nonsmokers were 0.31
      (0.08-1.24), 0.17 (0.04-0.75), 0.17 (0.05-0.60), and 0.11 (0.03-0.51),
      respectively, compared with the smokers. CONCLUSIONS: Preoperative smoking
      abstinence of longer than 3 weeks reduces the incidence of impaired wound healing
      among patients who have undergone reconstructive head and neck surgery.

PMID- 15851874
TI  - Anaphylaxis during anesthesia in Norway: a 6-year single-center follow-up study.
AB  - BACKGROUND: Several studies have recognized neuromuscular blocking agents as the
      most common cause of anaphylaxis during general anesthesia, but the reported
      frequencies vary considerably between countries. In Norway, the issue has raised
      special concern because of reports from the Norwegian Medicines Agency that
      suggest a high prevalence. This article presents the results from a standardized
      allergy follow-up examination of 83 anaphylactic reactions related to general
      anesthesia performed at one allergy center in Bergen, Norway. METHODS: Eighty
      three cases were examined during the 6-yr period of 1996-2001. The diagnostic
      protocol consisted of case history, serum tryptase measurements, specific
      immunoassays, and skin tests. RESULTS: Immunoglobulin E-mediated anaphylaxis was
      established in 71.1% of the cases, and neuromuscular blocking agents were by far
      the most frequent allergen (93.2%). Suxamethonium was the most frequently
      involved substance, followed by rocuronium and vecuronium. The few reactions in
      which other allergies could be detected were mainly linked to latex (3.6%).
      CONCLUSIONS: Neuromuscular blocking agents were the dominating antigens causing
      immunoglobulin E-mediated anaphylaxis in this study. The data could not be used
      for estimation of the incidence of allergy toward neuromuscular blocking agents
      in Norway. Larger patient samples, standardization of reporting, and diagnostic
      protocols should be pursued by network formation to produce data more suitable
      for epidemiologic research.

PMID- 15851875
TI  - Effect of metoclopramide on gastric fluid volumes in diabetic patients who have
      fasted before elective surgery.
AB  - BACKGROUND: Diabetes-induced gastroparesis is believed to increase fasting
      gastric fluid volume before elective surgery. Metoclopramide is routinely
      administered preoperatively to reduce gastric fluid volume in these patients.
      This study compared nondiabetic controls to non-insulin-dependent and insulin
      dependent diabetics to determine the effect of metoclopramide, administered
      before surgery, on gastric volumes in patients who fasted before surgery.
      METHODS: Control and diabetic patients fasted preoperatively before receiving
      either placebo or 10 mg intravenous metoclopramide 20 min before induction of
      anesthesia. After intubation, a gastric tube was placed, and stomach contents
      were aspirated with volumes compared among the groups. RESULTS: Both groups of
      diabetic patients were older than the control group, and insulin-dependent
      patients had a higher incidence of comorbidities compared with the non-insulin
      dependent group. Fasting blood sugar and hemoglobin A1C values were higher in
      both insulin-dependent and non-insulin-dependent patients. Gastric fluid volumes
      were similar in control, non-insulin-dependent, and insulin-dependent patients
      (8.0 +/- 2.6 vs. 9.6 +/- 4.1 vs. 17.7 +/- 2.5 ml, respectively). In insulin
      dependent diabetic patients, metoclopramide decreased gastric volume compared
      with placebo treatment (17.7 +/- 2.5 vs. 7.8 +/- 2.9 ml; P = 0.027). After
      stratification, a subpopulation of patients with poorly controlled diabetes,
      regardless of type, were identified to have increased gastric residual volumes.
      CONCLUSION: In elective surgical patients who have fasted before surgery, gastric
      volumes are minimal, even in diabetics with severe neuropathic symptoms.
      Metoclopramide prophylaxis to reduce gastric volumes seems to be unnecessary
      unless the patient has a prolonged history of poor blood glucose control.

PMID- 15851876
TI  - Endoscopic study of mechanisms of failure of endotracheal tube advancement into
      the trachea during awake fiberoptic orotracheal intubation.
AB  - BACKGROUND: Advancing the endotracheal tube (ETT) over a flexible bronchoscope
      (FB) during awake fiberoptic orotracheal intubation is often impeded. The goal of
      this study was to identify the sites and mechanisms that inhibit the passing of
      the ETT into the trachea. METHODS: Forty-five consenting patients underwent a
      clinically indicated awake fiberoptic orotracheal intubation. After topical
      anesthesia, nerve block, or both, an awake fiberoptic orotracheal intubation was
      performed. The placement of the FB and advancement of the ETT over the FB were
      videotaped using a second nasally inserted FB. An otolaryngologist later reviewed
      the videotaped data. RESULTS: The right arytenoid or the interarytenoid soft
      tissues inhibited advancement of the ETT in 42 and 11% of all patients,
      respectively. In all cases in which the FB was located on the right side of the
      larynx, failure of ETT advancement almost always occurred at the right arytenoid.
      Withdrawing the ETT and rotating it 90 degrees counterclockwise resulted in
      successful intubation on the second, third, and fourth attempts in 26.6, 20, and
      0.7% of patients, respectively. CONCLUSION: The right arytenoid frequently
      inhibits advancement of the ETT over the FB into the trachea during awake
      fiberoptic orotracheal intubation. The FB position in the larynx before tube
      advancement and the orientation of the ETT are relevant factors in failure of
      advancement of the ETT into the trachea. The authors recommend positioning the FB
      in the center of the larynx and orienting the bevel of the ETT to face
      posteriorly during the first attempt at intubation.

PMID- 15851877
TI  - Onset and duration of rocuronium-induced neuromuscular blockade in patients with
      Duchenne muscular dystrophy.
AB  - BACKGROUND: In patients with Duchenne muscular dystrophy (DMD) the response to
      nondepolarizing muscle relaxants is scarcely documented and conflicting. The
      current study was conducted to determine the time to peak effect and the time for
      complete spontaneous recovery after a single dose of 0.6 mg/kg of rocuronium in
      patients with DMD. METHODS: Twenty-four patients (12 with DMD, 12 controls, aged
      10-16 yr) were studied. All patients were anesthetized with propofol and
      fentanyl/remifentanil. Neuromuscular transmission was monitored by
      acceleromyography. After induction all patients received a single dose of 0.6
      mg/kg of rocuronium. The complete time course of onset and spontaneous recovery
      were recorded RESULTS: Significant (P < 0.01) increase in the onset times to 95%
      neuromuscular block was observed in DMD patients (median, 203 s; range, 90-420 s)
      compared with controls (median, 90 s; range, 60-195 s). The time between
      rocuronium administration and recovery of first twitch of the train-of-four to
      90% was significantly (P < 0.01) prolonged in DMD compared with controls (median,
      132 min; range, 61-209 min versus 39 min; 22-55 min). The recovery index was also
      significantly prolonged in the DMD group compared with controls (median, 28 min,
      range, 15-70 min versus 8 min; 3-14 min). CONCLUSIONS: The most striking and
      surprising result of this study is the delayed onset of blockade in DMD after a
      standard dose of rocuronium. This effect should be kept in mind in situations
      when a rapid airway protection is necessary in DMD patients. The documented very
      long recovery from rocuronium-induced block emphasizes the need for careful
      assessment of neuromuscular function in DMD patients.

PMID- 15851878
TI  - Sevoflurane blocks cholinergic synaptic transmission postsynaptically but does
      not affect short-term potentiation.
AB  - BACKGROUND: As compared with their effects on both inhibitory and excitatory
      synapses, little is known about the mechanisms by which general anesthetics
      affect synaptic plasticity that forms the basis for learning and memory at the
      cellular level. To test whether clinically relevant concentrations of sevoflurane
      affect short-term potentiation involving cholinergic synaptic transmission, the
      soma-soma synapses between identified, postsynaptic neurons were used. METHODS:
      Uniquely identifiable neurons visceral dorsal 4 (presynaptic) and left pedal
      dorsal 1 (postsynaptic) of the mollusk Lymnaea stagnalis were isolated from the
      intact ganglion and paired overnight in a soma-soma configuration. Simultaneous
      intracellular recordings coupled with fluorescent imaging of the FM1-43 dye were
      made in either the absence or the presence of sevoflurane. RESULTS: Cholinergic
      synapses, similar to those observed in vivo, developed between the neurons, and
      the synaptic transmission exhibited classic short-term, posttetanic potentiation.
      Action potential-induced (visceral dorsal 4), 1:1 excitatory postsynaptic
      potentials were reversibly and significantly suppressed by sevoflurane in a
      concentration-dependent manner. Fluorescent imaging with the dye FM1-43 revealed
      that sevoflurane did not affect presynaptic exocytosis or endocytosis; instead,
      postsynaptic nicotinic acetylcholine receptors were blocked in a concentration
      dependent manner. To test the hypothesis that sevoflurane affects short-term
      potentiation, a posttetanic potentiation paradigm was used, and synaptic
      transmission was examined in either the presence or the absence of sevoflurane.
      Although 1.5% sevoflurane significantly reduced synaptic transmission between the
      paired cells, it did not affect the formation or retention of posttetanic
      potentiation at this synapse. CONCLUSIONS: This study demonstrates that
      sevoflurane blocks cholinergic synaptic transmission postsynaptically but does
      not affect short-term synaptic plasticity at the visceral dorsal 4-left pedal
      dorsal 1 synapse.

PMID- 15851879
TI  - Xenon attenuates cerebral damage after ischemia in pigs.
AB  - BACKGROUND: Cerebral blood flow may be compromised in a variety of anesthetic
      procedures, and ischemic cerebral complications represent the leading cause of
      morbidity after cardiac operations. With the growing importance of
      neuroprotective strategies, the current study was designed to determine whether
      xenon would attenuate cardiac arrest-induced brain injury in pigs. METHODS:
      Twenty-four pigs (aged 12-16 weeks) were investigated in a randomized design.
      General hemodynamics, intracranial pressure, brain tissue oxygenation, and
      cerebral microdialysis parameters were investigated. The animals were assigned to
      two groups to receive anesthesia with either xenon (75%) in oxygen (25%) or total
      intravenous anesthesia combined with air in oxygen (25%) ventilation 15 min
      before cardiac arrest. After induction (t0) of cardiac arrest of 4 min,
      cardiopulmonary resuscitation was performed for 1 min, and the induced
      ventricular fibrillation was terminated by electrical defibrillation. The
      investigation time was 240 min. RESULTS: Approximately 60 s after cardiac arrest,
      brain tissue oxygenation decreased to a critical level of less than 5 mmHg,
      paralleled by a decrease in electroencephalographic activity. Glycerol as a
      damage marker increased significantly (> 200 m; P < 0.05), with a peak 90 min
      after cardiac arrest in both groups. Glycerol concentrations during reperfusion
      were significantly lower and normalized faster in the xenon group as compared
      with the total intravenous anesthesia group. CONCLUSION: Although the primary
      ischemic lesion in this model was similar in both groups, the cerebral
      microdialysis data show that xenon induces a differential neurochemical benefit
      in cerebral cell damage and metabolism as compared with total intravenous
      anesthesia in vivo during cerebral reperfusion after cardiac arrest in a pig
      model.

PMID- 15851880
TI  - Volatile anesthetics enhance flash-induced gamma oscillations in rat visual
      cortex.
AB  - BACKGROUND: The authors sought to understand neural correlates of anesthetic
      induced unconsciousness. Cortical gamma oscillations have been associated with
      neural processes supporting conscious perception, but the effect of general
      anesthesia on these oscillations is controversial. In this study, the authors
      examined three volatile anesthetics, halothane, isoflurane, and desflurane, and
      compared their effects on flash-induced gamma oscillations in terms of equivalent
      concentrations producing the loss of righting reflex (1 minimum alveolar
      concentration for the loss of righting [MAC(LR)]). METHODS: Light flashes were
      presented every 5 s for 5 min, and event-related potentials were recorded from
      primary visual cortex of 15 rats with a chronically implanted bipolar electrode
      at increasing anesthetic concentrations (0-2.4 MAC(LR)). Early cortical response
      was obtained by averaging poststimulus (0-100 ms) potentials filtered at 20-60 Hz
      across 60 trials. Late (100-1,000 ms) gamma power was calculated using multitaper
      power spectral technique. Wavelet decomposition was used to determine spectral
      and temporal distributions of gamma power. RESULTS: The authors found that (1)
      halothane, isoflurane, and desflurane enhanced the flash-evoked early cortical
      response in a concentration-dependent manner; (2) the effective concentration for
      this enhancement was the lowest for isoflurane, intermediate for halothane, and
      the highest for desflurane when compared at equal fractions of the concentration
      that led to a loss of righting; (3) the power of flash-induced late (> 100 ms)
      gamma oscillations was augmented at intermediate concentrations of all three
      anesthetic agents; and (4) flash-induced gamma power was not reduced below waking
      baseline even in deep anesthesia. CONCLUSIONS: These findings suggest that a
      reduction in flash-induced gamma oscillations in rat visual cortex is not a
      unitary correlate of anesthetic-induced unconsciousness.

PMID- 15851881
TI  - Influence of hypovolemia on the electroencephalographic effect of isoflurane in a
      swine model.
AB  - BACKGROUND: Hypovolemia alters the effect of several intravenous anesthetics by
      influencing pharmacokinetics and end-organ sensitivity. The authors investigated
      the influence of hypovolemia on the effect of an inhalation anesthetic,
      isoflurane, in a swine hemorrhage model. METHODS: Eleven swine were studied.
      After animal preparation with inhalation of 2% isoflurane anesthesia, the
      inhalation concentration was decreased to 0.5% and maintained at this level for
      25 min before being returned to 2% (control). After 25 min, hypovolemia was
      induced by removing 14 ml/kg of the initial blood volume via an arterial
      catheter. After a 25-min stabilization period, the inhalation concentration was
      decreased to 0.5%, maintained at this level for 25 min, and then returned to 2%
      (20% bleeding). After another 25 min, a further 7 ml/kg blood was collected, and
      the inhalation concentration was altered as before (30% bleeding). End-tidal
      isoflurane concentrations and an electroencephalogram were recorded throughout
      the study. Spectral edge frequency was used as a measure of the isoflurane
      effect, and pharmacodynamics were characterized using a sigmoidal inhibitory
      maximal effect model for the spectral edge frequency versus end-tidal
      concentration. RESULTS: There was no significant difference in the effect of
      isoflurane among the conditions used. Hypovolemia did not shift the concentration
      effect relation (the effect site concentration that produced 50% of the maximal
      effect was 1.2 +/- 0.2% under control conditions, 1.2 +/- 0.2% with 20% bleeding,
      and 1.1 +/- 0.2% with 30% bleeding). CONCLUSIONS: Hypovolemia does not alter the
      electroencephalographic effect of isoflurane, in contrast to several intravenous
      anesthetics.

PMID- 15851882
TI  - Selective thromboxane A2 synthase inhibition by OKY-046 prevents cardiopulmonary
      dysfunction after ovine smoke inhalation injury.
AB  - BACKGROUND: Because thromboxane A2 is implicated in the pathophysiology of acute
      lung injury, the aim of this study was to evaluate the effects of selective
      thromboxane A2 synthase inhibition on cardiopulmonary function in the
      experimental setting of severe smoke inhalation injury. METHODS: Sixteen adult
      sheep were operatively instrumented for chronic study. The injured intervention
      group was treated with the selective thromboxane A2 synthase inhibitor OKY-046,
      whereas the injured control group received only the vehicle (n = 8 each).
      RESULTS: The progressive increase in thromboxane B2 lung lymph concentrations in
      control animals was associated with increased transvascular fluid flux, augmented
      resistances in the pulmonary and systemic circulation, and a reciprocal decrease
      in cardiac output. In addition, end-systolic pressure-diameter relation and
      maximum +dp/dt were markedly depressed as compared with baseline (24 h: 14.3 +/-
      0.9 vs. 8.9 +/- 0.5 mmHg/mm and 2,120 +/- 50 vs. 1,915 +/- 40 mmHg/s,
      respectively; each P < 0.05). Infusion of OKY-046 significantly inhibited
      pulmonary thromboxane B2 delivery, attenuated the early increase in pulmonary
      vascular resistance, and blocked the increase in systemic vascular resistance. In
      addition, OKY-046 blunted and delayed the decrease in cardiac output and
      maintained end-systolic pressure-diameter relation, +dp/dt, and lung lymph flow
      at baseline values. CONCLUSIONS: These findings suggest that selective
      thromboxane A2 synthase inhibition may represent a goal-directed therapeutic
      approach to alleviate cardiovascular and pulmonary dysfunction in the setting of
      smoke inhalation injury.

PMID- 15851883
TI  - Modulation of gamma-aminobutyric acid type A receptor-mediated spontaneous
      inhibitory postsynaptic currents in auditory cortex by midazolam and isoflurane.
AB  - BACKGROUND: Anesthetic agents that target gamma-aminobutyric acid type A
      (GABA(A)) receptors modulate cortical auditory evoked responses in vivo, but the
      cellular targets involved are unidentified. Also, for agents with multiple
      protein targets, the relative contribution of modulation of GABA(A) receptors to
      effects on cortical physiology is unclear. The authors compared effects of the
      GABA(A) receptor-specific drug midazolam with the volatile anesthetic isoflurane
      on spontaneous inhibitory postsynaptic currents (sIPSCs) in pyramidal cells of
      auditory cortex. METHODS: Whole cell recordings were obtained in murine brain
      slices at 34 degrees C. GABA(A) sIPSCs were isolated by blocking ionotropic
      glutamate receptors. Effects of midazolam and isoflurane on time course,
      amplitude, and frequency of sIPSCs were measured. RESULTS: The authors detected
      no effect of midazolam at 0.01 microM on sIPSCs, whereas midazolam at 0.1 and 1
      microM prolonged the decay of sIPSCs by approximately 25 and 70%, respectively.
      Isoflurane at 0.1, 0.25, and 0.5 mm prolonged sIPSCs by approximately 45, 150,
      and 240%, respectively. No drug-specific effects were observed on rise time or
      frequency of sIPSCs. Isoflurane at 0.5 mm caused a significant decrease in sIPSC
      amplitude. CONCLUSIONS: The dose dependence of isoflurane effects on GABA(A)
      sIPSCs in pyramidal cells is consistent with effects on auditory evoked response
      in vivo. By contrast, comparable effects of midazolam on GABA(A) sIPSCs arise at
      concentrations exceeding those currently thought to be achieved in vivo,
      suggesting that the cellular targets of midazolam reside elsewhere in the
      thalamocortical circuit or that the concentration of midazolam reached in the
      brain is higher than currently believed.

PMID- 15851884
TI  - Clinically relevant concentrations of propofol but not midazolam alter in vitro
      dendritic development of isolated gamma-aminobutyric acid-positive interneurons.
AB  - BACKGROUND: Recent laboratory studies showed that exposure to supraclinical
      concentrations of propofol can induce cell death of immature neurons. However, no
      data are available regarding the effects of clinically relevant concentrations of
      this agent on neuronal development. The authors addressed this issue by
      evaluating the effect of propofol on dendritic growth and arbor expansion of
      developing gamma-aminobutyric acid-positive (GABAergic) interneurons. METHODS:
      Immature neuroblasts were isolated from the newborn rat subventricular zone and
      differentiated into GABAergic interneurons in culture. In addition to cell death,
      the effects of increasing concentrations and durations of propofol exposure on
      neuronal dendritic development were evaluated using the following morphologic
      parameters: total dendritic length, primary dendrites, branching point, and
      Scholl analysis. RESULTS: The authors demonstrate that propofol induced cell
      death of GABAergic neurons at concentrations of 50 microg/ml or greater. As
      little as 1 microg/ml propofol significantly altered several aspects of dendritic
      development, and as little as 4 h of exposure to this agent resulted in a
      persistent decrease in dendritic growth. In contrast, application of midazolam
      did not affect neuronal development. CONCLUSION: Short-term exposure of immature
      developing GABAergic neurons to clinically relevant concentrations of propofol
      can induce long-term changes in dendritic arbor development. These results
      suggest that propofol anesthesia during central nervous system development could
      interfere with the molecular mechanisms driving the differentiation of GABAergic
      neurons and thus could potentially lead to impairment of neural networks.

PMID- 15851885
TI  - Effect of bupivacaine and levobupivacaine on exocytotic norepinephrine release
      from rat atria.
AB  - BACKGROUND: The cardiotoxic mechanism of local anesthetics may include
      interruption of cardiac sympathetic reflexes. The authors undertook this
      investigation to determine if clinically relevant concentrations of bupivacaine
      and levobupivacaine interfere with exocytotic norepinephrine release from cardiac
      sympathetic nerve endings. METHODS: Rat atria were prepared for measurements of
      twitch contractile force and [H]-norepinephrine release. After nerve endings were
      loaded with [H]-norepinephrine, the tissue was electrically stimulated in 5-min
      episodes during 10 10-min sampling periods. After each period, a sample of bath
      fluid was analyzed for radioactivity and [H]-norepinephrine release was expressed
      as a fraction of tissue counts. Atria were exposed to buffer alone during
      sampling periods 1 and 2 (S1 and S2). Control atria received saline (100 microl
      each, n = 6 atria) in S3-S10. Experimental groups (n = 6 per group) received
      either bupivacaine or levobupivacaine at concentrations (in microM) of 5 (S3-S4),
      10 (S5-S6), 30 (S7-S8), and 100 (S9-S10). RESULTS: Bupivacaine and
      levobupivacaine decreased stimulation-evoked fractional [H]-norepinephrine
      release with inhibitory concentration 50% values of 5.1 +/- 0.5 and 6.1 +/- 1.3
      microM. The inhibitory effect of both local anesthetics (approximately 70%)
      approached that of tetrodotoxin. Local anesthetics abolished the twitch
      contractions of atria with inhibitory concentration 50% values of 12.6 +/- 5.0
      microM (bupivacaine) and 15.7 +/- 3.9 microM (levobupivacaine). In separate
      experiments, tetrodotoxin inhibited twitch contractile force by only 30%.
      CONCLUSIONS: The results indicate that clinically relevant cardiotoxic
      concentrations of bupivacaine and levobupivacaine markedly depress cardiac
      sympathetic neurotransmission. A possible mechanism of local anesthetics in
      reducing evoked norepinephrine release from sympathetic endings is blockade of
      tetrodotoxin-sensitive fast sodium channels.

PMID- 15851886
TI  - Volume turnover kinetics of fluid shifts after hemorrhage, fluid infusion, and
      the combination of hemorrhage and fluid infusion in sheep.
AB  - BACKGROUND: Hemorrhage is commonly treated with intravenous infusion of
      crystalloids. However, the dynamics of fluid shifts between body fluid spaces are
      not completely known, causing contradictory recommendations regarding timing and
      volume of fluid infusions. The authors have developed a turnover model that
      characterizes these fluid shifts. METHODS: Conscious, chronically instrumented
      sheep (n = 12) were randomly assigned to three protocol groups: infusion of 25
      ml/kg of 0.9% saline over 20 min (infusion only), hemorrhage of 300 ml (7.8 +/-
      1.1 ml/kg) over 5 min (hemorrhage only), and hemorrhage of 300 ml over 5 min
      followed by infusion as noted above (hemorrhage plus infusion). A two-compartment
      volume turnover kinetic model containing seven model parameters was fitted to
      data obtained by repeated sampling of hemoglobin concentration and urinary
      excretion. RESULTS: The volume turnover model successfully predicted fluid
      shifts. Mean baseline volumes of the central and tissue compartments were 1799 +/
      1276 ml and 7653 +/- 5478 ml, respectively. Immediate fluid infusion failed to
      prevent hemorrhage-induced depression of cardiac output and diuresis. The model
      suggested that volume recruitment to the central compartment after hemorrhage was
      primarily achieved by mechanisms other than volume equilibration between the two
      model compartments. CONCLUSION: Volume turnover kinetics is a promising tool for
      explaining fluid shifts between body compartments after perturbations such as
      hemorrhage and intravenous fluid infusions. The pronounced inhibition of renal
      output after hemorrhage prevailed regardless of fluid infusion and caused fluid
      retention, which expanded the tissue compartment.

PMID- 15851887
TI  - Intravenous versus nebulized ceftazidime in ventilated piglets with and without
      experimental bronchopneumonia: comparative effects of helium and nitrogen.
AB  - BACKGROUND: Lung deposition of intravenous cephalosporins is low. The lung
      deposition of equivalent doses of ceftazidime administered either intravenously
      or by ultrasonic nebulization using either nitrogen-oxygen or helium-oxygen as
      the carrying gas of the aerosol was compared in ventilated piglets with and
      without experimental bronchopneumonia. METHODS: Five piglets with noninfected
      lungs and 5 piglets with Pseudomonas aeruginosa experimental bronchopneumonia
      received 33 mg/kg ceftazidime intravenously. Ten piglets with noninfected lungs
      and 10 others with experimental P. aeruginosa bronchopneumonia received 50 mg/kg
      ceftazidime by ultrasonic nebulization. In each group, the ventilator was
      operated in half of the animals with a 65%/35% helium-oxygen or nitrogen-oxygen
      mixture. Animals were killed, and multiple lung specimens were sampled for
      measuring ceftazidime lung tissue concentrations by high-performance liquid
      chromatography. RESULTS: As compared with intravenous administration,
      nebulization of ceftazidime significantly increased lung tissue concentrations
      (17 +/- 13 vs. 383 +/- 84 microg/g in noninfected piglets and 10 +/- 3 vs. 129 +/
      108 microg/g in piglets with experimental bronchopneumonia; P < 0.001). The use
      of a 65%/35% helium-oxygen mixture induced a 33% additional increase in lung
      tissue concentrations in noninfected piglets (576 +/- 141 microg/g; P < 0.001)
      and no significant change in infected piglets (111 +/- 104 microg/g). CONCLUSION:
      Nebulization of ceftazidime induced a 5- to 30-fold increase in lung tissue
      concentrations as compared with intravenous administration. Using a helium-oxygen
      mixture as the carrying gas of the aerosol induced a substantial additional
      increase in lung deposition in noninfected piglets but not in piglets with
      experimental bronchopneumonia.

PMID- 15851888
TI  - For outpatient rotator cuff surgery, nerve block anesthesia provides superior
      same-day recovery over general anesthesia.
AB  - BACKGROUND: Both general and nerve block anesthesia are effective for shoulder
      surgery. For outpatient surgery, it is important to determine which technique
      provides more efficient recovery. The authors' goal was to compare nerve block
      with general anesthesia with respect to recovery profile and patient satisfaction
      after rotator cuff surgery. METHODS: In this clinical trial, 50 consenting
      outpatients (aged 18-70 yr) were randomly assigned to receive either fast-track
      general anesthesia followed by bupivacaine (0.25%) wound infiltration or
      interscalene brachial plexus block (0.75% ropivacaine), each under standardized
      protocols. Blinded recovery room nurses assessed the need for pain treatment and
      rated patient eligibility for bypass of the phase 1 postanesthesia care unit and
      for discharge home. Patients were followed up for 2 weeks postoperatively. The
      primary outcome measures were postanesthesia care unit bypass and same-day
      discharge. Other same-day recovery outcomes included severity of and treatment
      for pain and time to ambulation. Postoperative outcomes at home included
      satisfaction with the anesthesia technique and absence of complications (at 2
      weeks). RESULTS: Patients who received nerve block (vs. general anesthesia)
      bypassed the postanesthesia care unit more frequently (76 vs. 16%; P < 0.001),
      reported less pain, ambulated earlier, were ready for home discharge sooner (123
      vs. 286 min; P < 0.001), had no unplanned hospital admissions (vs. 4 of 25
      patients who underwent general anesthesia; P = 0.05), and were more satisfied
      with their care. No complications were reported in either treatment group.
      CONCLUSIONS: Nerve block anesthesia for outpatient rotator cuff surgery provides
      several same-day recovery advantages over general anesthesia.

PMID- 15851889
TI  - Intravenous butorphanol, meperidine, and their combination relieve pain and
      distress in women in labor.
AB  - BACKGROUND: Systemic opioids are commonly administered during labor, but their
      efficacy has been recently questioned. In addition, laboratory and clinical
      studies provide a strong rationale for combining mu- and kappa-opioid receptor
      agonists for analgesia. The authors therefore studied, using validated intensity
      and affective scales and definitions of effective pain relief, the efficacy of
      intravenous meperidine, butorphanol, and their combination for labor analgesia.
      METHODS: Healthy women with singleton term pregnancy requesting analgesia during
      active labor were studied. Women were randomly assigned to receive 50 mg
      meperidine, 1 mg butorphanol, or 25 mg meperidine plus 0.5 mg butorphanol (n =
      15/group). Pain intensity was assessed using a 0-10 numerical rating scale, and
      affective magnitude was assessed using a ratiometric descriptive scale before
      drug administration and between the sixth and seventh uterine contractions after
      drug administration. RESULTS: All three treatments reduced pain intensity
      equally. Butorphanol alone did not reduce pain affective magnitude, whereas the
      other treatments did. There was a significant correlation between reduction in
      pain intensity and affective magnitude in all groups, with greater reductions in
      affective magnitude than intensity. Overall, 29% of women exhibited clinically
      meaningful pain relief, with no difference among groups. Groups did not differ in
      incidence of opioid-induced adverse effects. CONCLUSIONS: These doses of
      meperidine and butorphanol do reduce pain intensity and affective magnitude,
      although a minority of patients achieve meaningful pain relief as defined in
      multiple patient populations, including laboring women. Combination of these
      drugs did not improve their therapeutic benefit.

PMID- 15851890
TI  - Forty-eight hours of postoperative pain relief after total hip arthroplasty with
      a novel, extended-release epidural morphine formulation.
AB  - BACKGROUND: Epidural morphine has proven analgesic efficacy in the postoperative
      period and is widely used. This study evaluated the efficacy of extended-release
      epidural morphine (EREM; DepoDur; Endo Pharmaceuticals Inc., Chadds Ford, PA;
      SkyePharma, Inc., San Diego, CA) in providing pain relief for 48 h after surgery.
      METHODS: Patients (n = 200) scheduled to undergo total hip arthroplasty were
      randomized to receive a single dose of 15, 20, or 25 mg EREM or placebo. After
      surgery and after asking for pain medication, patients had access to intravenous
      patient-controlled analgesia fentanyl for breakthrough pain as needed.
      Postoperative intravenous patient-controlled analgesia fentanyl use, time to
      first postoperative fentanyl use, pain intensity at rest and with activity,
      patient and surgeon ratings of pain control, and adverse events were recorded.
      RESULTS: All EREM dosages reduced the mean (+/- SD) fentanyl use versus placebo
      (510 +/- 708 vs. 2,091 +/- 1,803 microg; P < 0.0001) and delayed the median time
      to first dose of fentanyl (21.3 vs. 3.6 h; P < 0.0001). All EREM groups had
      significantly improved pain control at rest through 48 h postdose (area under the
      curve [0-48 h]) compared with placebo (P < 0.0005). More EREM-treated patients
      rated their pain control as good or very good compared with placebo (at 24 h: 90
      vs. 65%, P < 0.0001; at 48 h: 83 vs. 67%, P < 0.05). No supplemental analgesia
      was needed in 25% of EREM-treated patients and 2% of placebo-treated patients at
      48 h (P < 0.05). The safety profile of EREM was consistent with that of other
      epidurally administered opioid analgesics. CONCLUSIONS: EREM provided significant
      postoperative pain relief over a 48-h period after hip surgery, without the need
      for indwelling epidural catheters.

PMID- 15851891
TI  - Intravenous lidocaine relieves spinal cord injury pain: a randomized controlled
      trial.
AB  - BACKGROUND: Neuropathic pain in spinal cord injury is a common challenging
      therapeutic condition. The current study examines the analgesic effect of the
      sodium channel blocker lidocaine on neuropathic pain in patients with spinal cord
      injury and the predictive role of concomitant evoked pain on pain relief with
      lidocaine. METHODS: Twenty-four spinal cord injury patients with neuropathic pain
      at or below the level of injury were randomized and completed a double-blind
      crossover trial of 5 mg/kg lidocaine and placebo infused over 30 min. Twelve
      patients reported evoked pain, and 12 patients had no evoked pain. Spontaneous
      and evoked pains were assessed using a visual analog scale and quantitative
      sensory testing. RESULTS: Lidocaine significantly reduced spontaneous pain in all
      patients (P < 0.01) and in each of the two groups with (P < 0.01) and without (P
      = 0.048) evoked pain, with no difference in number of responders (pain reduction
      > or = 33%) between the patients with (n = 6) and without (n = 5) evoked pain.
      Lidocaine significantly relieved both at-level and below-level neuropathic pain
      and decreased brush-evoked dysesthesia but not cold allodynia, pinprick
      hyperalgesia, or pain evoked by repetitive pinprick. CONCLUSIONS: Lidocaine
      reduced neuropathic pain at and below the level of injury irrespective of the
      presence or absence of evoked pain. Results are consistent with a central-acting
      effect of sodium channel blockers acting on neuronal hyperexcitability. Agents
      (such as anticonvulsants or antiarrhythmics) with sodium channel-blocking
      properties may be a treatment option for spinal cord injury pain.

PMID- 15851893
TI  - Assessing the past and shaping the future of anesthesiology: the 43rd Rovenstine
      Lecture.

PMID- 15851892
TI  - Perioperative acupuncture and related techniques.
AB  - Acupuncture and related techniques are increasingly practiced in conventional
      medical settings, and the number of patients willing to use these techniques is
      increasing. Despite more than 30 yr of research, the exact mechanism of action
      and efficacy of acupuncture have not been established. Furthermore, most aspects
      of acupuncture have yet to be adequately tested. Therefore, considerable
      controversy remains about the role of acupuncture in clinical medicine.
      Acupuncture apparently does not reduce volatile anesthetic requirement by a
      clinically important amount. However, preoperative sedation seems to be a
      promising application of acupuncture in perioperative settings. Acupuncture may
      be effective for postoperative pain relief but requires a high level of expertise
      by the acupuncture practitioner. Acupuncture and related techniques can be used
      for treatment and prophylaxis of postoperative nausea and vomiting in routine
      clinical practice in combination with or as an alternative to conventional
      antiemetics when administered before induction of general anesthesia.

PMID- 15851894
TI  - Extramedullary intrathecal catheter granuloma adherent to the conus medullaris
      presenting as cauda equina syndrome.

PMID- 15851895
TI  - Retrograde intubation around an in situ Combitube: a difficult airway management
      strategy.

PMID- 15851896
TI  - Novel system for complete removal of secretions within the endotracheal tube: the
      Mucus Shaver.

PMID- 15851898
TI  - Case series or uncontrolled clinical study?

PMID- 15851900
TI  - Pharmacodynamics of propofol during hemorrhagic shock.

PMID- 15851901
TI  - Depth of anesthesia monitors and shock.

PMID- 15851903
TI  - Is recall during sedation being confused with recall during general anesthesia?

PMID- 15851904
TI  - Respiratory distress after a deep cervical plexus block.

PMID- 15851907
TI  - In vitro and in vivo: the story of nonoxynol 9.
AB  - There is an urgent need to expand the range of interventions to prevent HIV
      transmission and acquisition, especially those that can be controlled by women.
      Microbicides, defined as antimicrobial products that can be applied topically for
      the prevention of HIV and other sexually transmitted infections, may offer one of
      the most promising preventive interventions, because they could be inexpensive,
      readily available, and widely acceptable. The first microbial product to be
      clinically evaluated contained Nonoxynol-9 (nonylpenoxypolyethoxyethanol [N-9]),
      a nonionic surfactant, as the active agent. This article presents a review of the
      in vitro, ex vivo, and animal model data on the safety of N-9 and a critical
      analysis of their predictive power based on the results of multiple safety and
      efficacy trials.

PMID- 15851908
TI  - Risk factors for HIV infection in injection drug users and evidence for onward
      transmission of HIV to their sexual partners in Chennai, India.
AB  - OBJECTIVES: Determining HIV prevalence in injection drug users (IDUs) and their
      regular sex partners in Chennai, India. METHODS: A total of 226 IDUs and their
      regular sex partners were enrolled during April-July 2003. After informed consent
      was obtained, a semistructured questionnaire was administered and serum was
      tested for HIV antibody. RESULTS: The HIV seroprevalence was 30% (68/226) in IDUs
      and 5% in their regular sex partners (11/226). While in 25% of couples only the
      male partner was HIV positive, 5% of the couples were concordant for HIV
      infection and 70% were HIV negative. Fifty-seven percent of the HIV-positive IDUs
      and 45% of the HIV-infected women thought that they had "no chance" or "very
      little chance" of getting HIV, reflecting low HIV risk perception. More than 20%
      IDUs reported borrowing or lending of injection equipment. In univariate analyses
      "sex" and "condom use" with sex workers had no bearing but "more than twice a day
      injecting frequency," "history of incarceration," "tattoos," "recruitment from
      northern part of the city," and ever-injecting drugs in drug-selling places had
      significant association with HIV infection in IDUs. In an adjusted model, the
      odds of HIV infection were 2 times higher among IDUs who had ever injected drugs
      in drug-selling places and 6 times higher in those who were recruited from the
      northern part of central Chennai. CONCLUSION: Reducing sharing of injection
      equipment and unsafe tattooing through targeted and environmental interventions,
      increasing HIV risk perception, and promoting safer sex practices among IDUs and
      their sex partners are urgent program needs.

PMID- 15851909
TI  - T-cell activation and memory phenotypes in cerebrospinal fluid during HIV
      infection.
AB  - We characterized T cell phenotypes in 74 paired blood and cerebrospinal fluid
      (CSF) samples of HIV-infected and uninfected persons using four-color flow
      cytometry. CD4+ and CD8+ T cells subsets were further characterized by
      identifying activated/resting and memory/naive subsets in CSF and blood using the
      markers CD38/HLA-DR and CD45RA/CD62L, respectively. With and without HIV
      infection, the proportion of CD4+ T cells and memory T cells among T cells in CSF
      was higher compared to blood. In HIV-infection, activated CD4+ and CD8+ T cells
      in CSF were more abundant than in uninfected controls. As expected, combination
      antiretroviral therapy (ART) reduced T cell activation in CSF and blood.

PMID- 15851910
TI  - High plasma levels of intact and cleaved soluble urokinase receptor reflect
      immune activation and are independent predictors of mortality in HIV-1-infected
      patients.
AB  - BACKGROUND: High blood levels of soluble urokinase receptor (suPAR) measured by
      enzyme-linked immunoassay (ELISA) (bulk measurement of 3-domain and 2-domain
      suPAR [suPAR(I-III), suPAR(II-III)], and suPAR(I-III) ligand complexes) strongly
      predict mortality in HIV-1-infected patients. This study investigated plasma
      levels of suPAR(I-III), suPAR(II-III), and 1-domain suPAR [suPAR(I)] and their
      predictive value for survival in HIV patients. METHODS: Plasma suPAR was measured
      by ELISA and 3 different time-resolved fluorescence immunoassays detecting
      suPAR(I-III), suPAR(I-III) plus suPAR(II-III), and suPAR(I) in 99 HIV patients
      and 59 healthy individuals. RESULTS: Plasma suPAR(I-III), suPAR(II-III), and
      suPAR(I) were increased in HIV patients and increased with HIV disease
      progression (P < 0.001 for all). In multivariate linear regression analysis,
      soluble immune activation markers and hemoglobin were independent predictors of
      plasma suPAR in HIV patients, whereas the neutrophil concentration was the only
      independent predictor of plasma suPAR in controls. In univariate Cox analysis,
      higher levels of suPAR(I-III), suPAR(II-III), and suPAR(I) predicted increased
      mortality risk (P < 0.001 for all). In multivariate Cox analysis adjusting for
      CD4+ count, HIV RNA, beta2-microglobulin, hemoglobin and clinical stage, higher
      levels of suPAR(I-III) and suPAR(II-III) were independent predictors of increased
      mortality risk (P < 0.05 for both), whereas suPAR(I) was not. CONCLUSIONS: Plasma
      levels of different suPAR forms are increased and associated with immune
      activation in HIV patients, and suPAR(I-III) and suPAR(II-III) are independent
      predictors of mortality in these patients.

PMID- 15851911
TI  - Absolute CD4 T-cell counting in resource-poor settings: direct volumetric
      measurements versus bead-based clinical flow cytometry instruments.
AB  - Flow cytometry is an accurate but expensive method to determine absolute CD4 cell
      counts. We compared different methods to measure absolute CD4 counts in blood
      samples from HIV-infected and uninfected subjects using a research/clinical flow
      cytometer (FACScan); a dedicated clinical instrument (FACSCount); and a
      volumetric, mobile, open-system flow cytometer equipped with 3 fluorescence and 2
      light scatter detectors (Cyflow SL blue). The FACScan and Cyflow were used as
      single-platform instruments, but they differ in running cost, which is a central
      factor for resource-poor settings. Direct volumetric and bead-based CD4
      measurements on the Cyflow were compared with 2 bead-based single-platform CD4
      measurements on the FACSCount and on FACScan (TruCount) in "Le Dantec" Hospital,
      Dakar, Senegal, using whole blood samples from 102 HIV+ and 28 HIV- subjects. The
      agreement between the various measurement methods was evaluated by Bland-Altman
      analysis. Volumetric CD4 measurements on the Cyflow using a no-lyse-no-wash
      (NLNW) procedure and a lyse-no-wash (LNW) procedure correlated well with each
      other (R2 = 0.98) and with CD4 measurements on the FACSCount (R2 = 0.97) and
      FACScan (R2 = 0.97), respectively. Red blood cell lysis had no negative effect on
      the accuracy of absolute CD4 counting on the Cyflow. An excellent correlation was
      observed between bead-based CD4 measurements on the Cyflow and CD4 measurements
      on the FACSCount (R2 = 0.99) and FACScan (R2 = 0.99). Rigid internal and external
      quality control monitoring and adequate training of technicians were considered
      essential to generate accurate volumetric CD4 measurements on the Cyflow.

PMID- 15851912
TI  - Biochemical and HIV-1 coreceptor properties of K26R, a new CCR5 Variant in
      China's Sichuan population.
AB  - Despite multiple exposures to HIV-1, some individuals remain uninfected. This
      resistance to HIV infection has been associated with homozygosity for a 32
      basepair deletion in the CCR5 receptor gene. This variant is frequent in
      caucasians but extremely rare in Asians and Africans. Identifying variations in
      the CCR5 gene that affect susceptibility to HIV infection in non-caucasians is
      therefore of great interest. In this report, we identify 5 CCR5 coding region
      variants in a Chinese population. The K26R mutation is an undescribed gene
      variant, whereas 228delK was already found in caucasians and G106R, C178R, and
      R223Q were previously described in Asian populations and functionally analyzed.
      As the function of K26R was still unknown, we focused our work on studying its
      chemokine receptor activity and HIV coreceptor properties compared with wild-type
      CCR5 and G106R, an already analyzed mutant taken as another control. We observed
      that K26R displayed alteration in MIP1-beta/CCL4 and RANTES/CCL5 ligand binding
      and exhibited a slightly decrease for HIV coreceptor properties.

PMID- 15851913
TI  - Increased cardiovascular disease risk indices in HIV-infected women.
AB  - Little is known regarding cardiovascular disease risk indices in HIV-infected
      women. This study investigated cardiovascular disease risk indices in 100
      consecutively recruited HIV-infected women and 75 healthy female control
      subjects. Subjects were recruited from hospital- and community-based health care
      providers. C-reactive protein (CRP), interleukin-6 (IL-6), adiponectin, lipid,
      and glucose levels were the main outcome measures. CT scan, dual-energy x-ray
      absorptiometry (DXA), and anthropometry were used to assess body composition.
      Although similar in age, weight, and racial composition, HIV-infected women
      demonstrated higher CRP (4.6 +/- 0.7 vs. 2.3 +/- 0.4 mg/L, P = 0.007), IL-6 (2.7
      +/- 0.2 vs. 1.8 +/- 0.1 pg/mL, P = 0.02), triglyceride (1.84 +/- 0.21 vs. 0.85 +/
      0.05 mM, P = 0.0002), 2-hour glucose after oral glucose challenge (6.88 +/- 0.22
      vs. 5.72 +/- 0.17 mM, P = 0.0003), and fasting insulin (81 +/- 8 vs. 45 +/- 2 pM,
      P = 0.0002) and lower high-density lipoprotein cholesterol (1.17 +/- 0.03 vs.
      1.45 +/- 0.05 mM, P < 0.0001) and adiponectin (5.4 +/- 0.3 vs. 7.6 +/- 0.5 mg/L,
      P = 0.0001) levels compared with the control population. HIV-infected women had
      more abdominal visceral fat and less extremity fat by CT and DXA scan and
      demonstrated a higher waist-to-hip ratio (WHR) than the control population.
      Within the HIV group, CRP and other indices were significantly related to body
      composition in stepwise regression models. Among all subjects, WHR, but not HIV
      status, was significantly related to CRP and other cardiovascular disease risk
      indices. HIV-infected women demonstrate significantly increased risk factors for
      cardiovascular disease in association with abnormal fat distribution.

PMID- 15851914
TI  - Oral glucose tolerance and insulin sensitivity are unaffected by HIV infection or
      antiretroviral therapy in overweight women.
AB  - OBJECTIVE: To assess the frequency of diabetes, prediabetes, and insulin
      resistance among a subset of participants in the Women's Interagency HIV Study
      (WIHS). DESIGN: Cross-sectional substudy nested within a prospective multicenter
      cohort study. Women underwent 75 g oral glucose tolerance testing. Diagnoses of
      diabetes and prediabetes were made according to the American Diabetes Association
      criteria, and insulin resistance was determined by area under the curve insulin
      and homeostasis model assessment values. SETTING: Six urban clinical sites in the
      United States (Brooklyn, NY; Bronx, NY; Washington, DC; Chicago, IL; San
      Francisco, CA; Los Angeles, CA) participate in the entire WIHS. The Bronx, NY,
      and San Francisco, CA, WIHS sites participated in this substudy. PARTICIPANTS: A
      total of 258 women, 88 HIV negative, 74 HIV positive not on highly active
      antiretroviral therapy (HAART), and 96 HIV positive taking HAART were enrolled in
      the study. MAIN OUTCOMES: Prevalence of diabetes, prediabetes, and insulin
      resistance was compared among the HIV-uninfected and HIV-infected women. RESULTS:
      The frequency of diabetes, prediabetes, or insulin resistance was unrelated to
      HIV status or antiretroviral treatment. Increasing body mass index was the only
      characteristic associated with the combined endpoints of diabetes and prediabetes
      (odds ratio = 1.104, P = 0.0002). CONCLUSIONS: Routine oral glucose tolerance
      testing of HIV-infected women is not supported by these findings. Elucidation of
      putative perturbations from HIV or antiretroviral medications requires direct
      studies of insulin resistance and beta-cell function.

PMID- 15851915
TI  - Increased dose of lopinavir/ritonavir compensates for efavirenz-induced drug-drug
      interaction in HIV-1-infected children.
AB  - BACKGROUND: Nucleoside reverse transcriptase inhibitor-sparing regimens have not
      yet been systematically evaluated in children. The nonnucleoside reverse
      transcriptase inhibitors nevirapine and efavirenz lower plasma levels of protease
      inhibitors in adults and children. Therefore, coadministration of
      lopinavir/ritonavir with nevirapine and efavirenz necessitates a 30% increase in
      the dose of lopinavir/ritonavir in adults. In children, the extent of the
      pharmacokinetic interaction between efavirenz and lopinavir/ritonavir has not yet
      been studied. OBJECTIVE: To investigate the pharmacokinetics of increased-dose
      (300/75 mg/m2 twice-daily) lopinavir/ritonavir with normal-dose (14 mg/kg once
      daily) efavirenz in HIV-1-infected children. METHODS: Steady-state
      pharmacokinetics of lopinavir and efavirenz were determined and compared with
      historical data. RESULTS: Fifteen children of median age 11.8 (range, 5.7-16.3)
      years were included. Area under the plasma concentration-time curve (AUC0-12),
      peak levels (Cmax), and trough levels (Cmin) of lopinavir were similar to
      historical data in adults and children. Medians (interquartile range) were 92.3
      (43.5-138.5) mg/L.h, 12.5 (6.9-16.7) mg/L, and 5.7 (1.3-8.0) mg/L, respectively.
      Efavirenz pharmacokinetics approximated previous data in adults and children.
      CONCLUSION: The increased dose of 300/75 mg/m2 twice-daily lopinavir/ritonavir
      compensates for the enzyme-inducing effect of efavirenz in HIV-infected children.

PMID- 15851916
TI  - Cost-effectiveness of enfuvirtide in treatment-experienced patients with advanced
      HIV disease.
AB  - OBJECTIVE: Enfuvirtide (ENF) has been shown to improve short-term virologic
      responses when given to highly treatment-experienced patients with advanced HIV
      disease. Because of the high cost of ENF compared with other antiretroviral
      agents, our objectives were to determine the potential long-term clinical impact
      and cost-effectiveness of ENF in these patients. METHODS: We used a computer
      simulation model of HIV disease to project life expectancy, quality-adjusted life
      expectancy, cost, and cost-effectiveness of ENF in treatment-experienced
      patients. Input data were from the T-20 versus Optimized Regimen Only (TORO) 1
      and 2 trials, 2 studies comparing ENF plus an optimized background regimen (OBR)
      with an OBR alone. RESULTS: ENF plus an OBR increased projected discounted
      quality-adjusted life expectancy from 45.4 months with an OBR alone to 54.9
      months, a difference of 9.5 quality-adjusted life-months. At the current annual
      ENF cost of US 18,500 dollars per year (in 2001 US dollars), the incremental cost
      effectiveness ratio for ENF plus an OBR was US 69,500 dollars per quality
      adjusted life-year (QALY) compared with an OBR alone. When 48-week virologic
      suppression rates for ENF plus an OBR were varied from a 50% reduction to a 250%
      increase in the suppression rate attributable to ENF, gains in quality-adjusted
      life expectancy ranged from 4.5 to 25.9 quality-adjusted life-months compared
      with an OBR alone, with cost-effectiveness ratios ranging from US 97,900 dollars
      per QALY to US 52,300 dollars per QALY gained. If ENF is continued after the HIV
      RNA level returns to the pretreatment baseline, the cost-effectiveness ratio
      increases to US 168,200 dollars per QALY. CONCLUSIONS: In highly treatment
      experienced patients, ENF plus an OBR provides substantial gains in quality
      adjusted life expectancy compared with an OBR alone. Although ENF plus an OBR is
      less cost-effective than other commonly used interventions in HIV disease, its
      use may be justified, given the poor prognosis of these patients and their
      otherwise limited options for antiretroviral therapy.

PMID- 15851917
TI  - Nonnucleoside reverse transcriptase inhibitor phenotypic hypersusceptibility can
      be demonstrated in different assays.
AB  - BACKGROUND: HIV-1 isolates harboring multiple nucleoside reverse transcriptase
      inhibitor (NRTI) resistance mutations are more susceptible ("hypersusceptible")
      to the nonnucleoside reverse transcriptase inhibitors (NNRTIs) than isolates
      lacking NRTI resistance mutations, but this has only been reported with a single
      cycle replication phenotypic assay. In fact, there was a report that a commercial
      multicycle assay did not readily detect hypersusceptibility. OBJECTIVE: To see
      whether NNRTI hypersusceptibility can be demonstrated in other types of
      phenotypic assays, including multicycle assays and enzyme inhibition assays.
      METHODS: The susceptibility of HIV-1 clones derived from different patients in
      multicycle assays was tested in peripheral blood mononuclear cells (PBMCs) and in
      an established cell line. In addition, the reverse transcriptase (RT) of many of
      these clones was expressed and their susceptibility tested in an RT inhibition
      assay. Nevirapine and efavirenz susceptibilities were tested and compared with a
      control wild-type virus or RT. RESULTS: Hypersusceptibility to nevirapine and
      efavirenz was detected using each of the methods described above. R values
      correlating the other methods with single-cycle assay values were between 0.66
      and 0.96. In addition to the high correlations, the different methods gave
      similar numeric results. CONCLUSIONS: NNRTI hypersusceptibility is readily seen
      in multicycle susceptibility assays and in enzyme inhibition assays.

PMID- 15851918
TI  - Sexual risk, nitrite inhalant use, and lack of circumcision associated with HIV
      seroconversion in men who have sex with men in the United States.
AB  - Men who have sex with men (MSM) continue to account for the largest number of new
      HIV infections in the United States, but limited data exist on independent risk
      factors for infection beyond the early 1990s. The HIV Network for Prevention
      Trials Vaccine Preparedness Study enrolled 3257 MSM in 6 US cities from 1995 to
      1997. HIV seroincidence was 1.55 per 100 person-years (95% confidence interval:
      1.23-1.95) over 18 months of follow-up. On multi-variable analysis using time
      dependent covariates, independent risk factors for HIV seroconversion were
      increased number of reported HIV-negative male sex partners (adjusted odds ratio
      (AOR) = 1.14 per partner, population attributable risk (PAR) = 28%), nitrite
      inhalant use (AOR = 2.2, PAR = 28%), unprotected receptive anal sex with an HIV
      unknown serostatus partner (AOR = 2.7, PAR = 15%) or HIV-positive partner (AOR =
      3.4, PAR = 12%), protected receptive anal sex with an HIV-positive partner (AOR =
      2.2, PAR = 11%), lack of circumcision (AOR = 2.0, PAR = 10%), and receptive oral
      sex to ejaculation with an HIV-positive partner (AOR = 3.8, PAR = 7%). Having a
      large number of male sex partners, nitrite inhalant use, and engaging in
      receptive anal sex explained the majority of infections in this cohort and should
      be targeted in prevention strategies for MSM.

PMID- 15851919
TI  - HIV sexual risk behavior over 36 months of follow-up in the world's first HIV
      vaccine efficacy trial.
AB  - Increased risk behavior among participants in HIV vaccine efficacy trials has
      been a concern. This study evaluated HIV sexual risk behavior among 5095 HIV
      negative men who have sex with men (MSM) and 308 women enrolled in a randomized,
      double-blind, placebo-controlled efficacy trial of a bivalent rgp120 vaccine at
      61 sites, primarily in North America. Sexual risk behavior data were collected at
      baseline and semiannually for 36 months. Overall, sexual risk behavior did not
      exceed baseline levels during the trial. Among MSM, younger age (< or =30 years),
      perceived assignment to vaccine, and nonblack race were associated with an
      increased probability of unprotected anal sex. Among women, unprotected vaginal
      sex initially decreased but was statistically equivalent to baseline by 24
      months, whereas unprotected vaginal sex with HIV-infected partners decreased from
      baseline, where it remained throughout the trial. HIV sexual risk behavior did
      not increase among trial participants; however, it was substantial throughout the
      trial. Consistently high levels of risk behavior and the association of these
      behaviors to perceived assignment and demographic variables underscore the need
      for vigilant HIV risk reduction counseling, informed consent, and educational
      processes in the context of HIV vaccine efficacy trials.

PMID- 15851920
TI  - Estimates of HIV incidence among persons testing for HIV using the sensitive/less
      sensitive enzyme immunoassy, New York City, 2001.
AB  - BACKGROUND: Estimates of the incidence of HIV infection among persons testing for
      HIV can be derived by applying a newly available serologic test to the diagnostic
      specimen of HIV-positive persons. Such estimates would enhance the targeting of
      HIV prevention resources and provide a sensitive outcome measure for prevention
      program evaluation. The goal of this investigation was to estimate the incidence
      of HIV infection among persons testing for HIV in New York City. METHODS: The
      study population consisted of persons testing for HIV in public settings in New
      York City during 2001 (n = 114,703). We applied a less sensitive enzyme
      immunoassay (LS-EIA) (Vironostika, BioMerieux, Durham, NC) to the diagnostic
      blood specimen of 1022 persons in whom HIV (non-AIDS) had been diagnosed for the
      first time in 2001. The distribution of transmission risk among HIV-negative
      persons--men who have sex with men (MSM), injection drug users (IDUs),
      heterosexuals-from a large telephone health survey was used to generate
      denominators for transmission risk groups. RESULTS: The 1022 persons tested by
      the LS-EIA represented 27% of all persons in whom HIV (non-AIDS) had been
      diagnosed in New York City during 2001. The incidence of HIV was estimated to be
      0.29% per year (95% CI: 0.20-0.38), and was significantly higher for men than
      women (rate ratio 3.6, 95% CI: 2.6-5.1), and HIV incidence increased with age.
      Male IDU and MSM testers had the highest HIV incidence rates: 2.7% per year (95%
      CI: 2.3-3.1) and 2.5% per year (95% CI: 2.1-2.8), respectively. CONCLUSIONS: Male
      IDUs and MSM may be good candidates for intensified targeting of HIV prevention
      resources in New York City.

PMID- 15851921
TI  - Comparison of three methods to measure HIV incidence among persons seeking
      voluntary, anonymous counseling and testing.
AB  - OBJECTIVES: The authors compared 3 practical methods to estimate human HIV
      incidence rates using existing data from persons seeking anonymous testing in San
      Francisco between 1996-2002. Each method was assessed for strengths and
      limitations. METHODS: Three different approaches were used to determine HIV
      incidence: one based on self-reported dates of prior tests, one based on linking
      records of prior tests using an anonymous unique testing code, and one based on
      the Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS). RESULTS:
      The 3 methods found comparable rates of seroconversion overall (1.0, 1.2, and 1.3
      per 100 person-years) and among men who have sex with men (1.4, 1.6, and 2.0 per
      100 person-years). Incidence for all 3 methods saw a peak during 1999 followed by
      a decline. Greatest variability of incidence was observed among lower-risk
      populations, in whom few infections were expected. CONCLUSIONS: The 3 methods had
      complementary strengths and limitations, which may prevent proper interpretation
      of HIV incidence if any one method is analyzed alone. HIV incidence rates among
      persons seeking HIV testing should be interpreted cautiously using corroborative
      data on risk behavior and sexually transmitted diseases and other contextual
      information.

PMID- 15851922
TI  - Maternal self-medication and provision of nevirapine to newborns by women in
      Rakai, Uganda.
AB  - To assess the effectiveness of maternal self-administration of nevirapine for
      prevention of mother-to-child transmission (MTCT) of HIV, we conducted a program
      to provide maternal and newborn doses of nevirapine to pregnant women in rural
      Uganda. Women provided blood for HIV testing and were offered voluntary
      counseling and testing (VCT) during annual community HIV surveys. HIV-positive
      women who accepted VCT were offered nevirapine tablets and syrup. Blood samples
      were collected postpartum from women and their babies. Infants were tested for
      HIV by polymerase chain reaction (PCR), and a subsample of maternal and infant
      blood was assayed for nevirapine. Among the 981 women tested for HIV, 900 (91.7%)
      accepted VCT, of whom 105 (11.7%) were HIV-positive. Ninety-three women accepted
      nevirapine, of whom 81 (87.1%) were followed postpartum; 75 (92.6%) reported
      receipt of the drug, and 69 reported taking the tablets (85.2%). There were 81
      liveborn babies (3 sets of twins), and 67 (84.8%) received the syrup. In a
      subsample of 25 mothers reporting receipt of the drug, nevirapine was detected in
      22 (88.0%) and 24 (96.0%) babies tested. PCR of 67 infant blood samples
      identified 5 HIV-positive (MTCT rate = 7.5%, 95% confidence interval [CI]: 0.3%
      16.6%). Mothers can administer nevirapine to themselves and their newborns and
      can achieve low rates of perinatal HIV infection.

PMID- 15851923
TI  - Lipodystrophy is associated with a low rate of treatment failure in HIV-positive
      patients switched to atazanavir.

PMID- 15851924
TI  - Impact of acid-suppressive therapy on virologic response to atazanavir-based
      regimens in antiretroviral-experienced patients: a case series.

PMID- 15851925
TI  - The role of apical instrumentation in root canal treatment: a review of the
      literature.
AB  - The issue of final apical preparation size remains controversial despite
      considerable clinical and in vitro research. The astute clinician must be aware
      of this research before choosing any instrumentation system because the informed
      clinician's decision must be guided by the best available evidenced-based
      information. This review article generated a Medline-based search strategy to
      disclose these studies and provides a critique and summary of the results.

PMID- 15851926
TI  - A systematic review of in vitro retrograde obturation materials.
AB  - The purpose of this review was two-fold: (a) to determine which retrograde
      obturation material(s) best prevents dye/ink penetration in vitro; and (b) to
      determine whether in vitro results agree with in vivo results. A MEDLINE search
      was conducted to identify in vitro studies published between January 1966 and
      October, week 4, 2003, conducted on human teeth, and published in English,
      German, or French language, testing the resistance to retrograde penetration of
      retrograde filling materials. The MEDLINE search identified 278 published
      articles. Of those, 115 studies examined the resistance to penetration of various
      retrograde filling materials, in vitro. Thirty-four studies met all the inclusion
      and validity criteria. The results indicate that, beyond 10 days in vitro, the
      most effective retrofilling materials, when measured by dye/ink penetration are:
      composites>glass ionomer cement>amalgam>orthograde gutta-percha>EBA. The results
      of these in vitro studies are not congruent with in vivo study results,
      suggesting a need to re-evaluate the clinical validity and importance of in vitro
      studies.

PMID- 15851927
TI  - Neutrophil elastase levels in periapical exudates of symptomatic and asymptomatic
      teeth.
AB  - The aim of this study was to determine neutrophil elastase levels (NE) in
      periapical exudates and to evaluate its relationship with clinical signs and
      symptoms of endodontically involved teeth. A total of 42 teeth with periapical
      periodontitis of 37 patients were clinically examined and spontaneous pain,
      swelling, pain on palpation or percussion, sinus tract formation and pus
      discharge were recorded. Additionally, periapical lesion size was measured on
      periapical radiographs. Periapical exudate samples were obtained during routine
      root canal treatment by using paper points. Enzyme levels were determined by
      spectrophotometric assays using the NE specific substrate N-methoxysuccinil-Ala
      Ala-Pro-Val-p-nitroanilide. The teeth with signs and symptoms showed higher NE
      levels than the teeth without symptoms (p<0.05). The differences were significant
      when NE levels were presented as total amounts instead of concentration. This
      study demonstrated that NE in periapical lesions related with clinical symptoms
      and total enzyme amount may be more reliable mode of data presentation.

PMID- 15851928
TI  - Anesthetic effectiveness of the supplemental intraligamentary injection,
      administered with a computer-controlled local anesthetic delivery system, in
      patients with irreversible pulpitis.
AB  - The purpose of this study was to determine the anesthetic effectiveness of the
      supplemental intraligamentary injection, administered with a computer-controlled
      local anesthetic delivery system, in mandibular posterior teeth diagnosed with
      irreversible pulpitis when the conventional inferior alveolar nerve block failed.
      Fifty-four emergency patients, diagnosed with irreversible pulpitis of a
      mandibular posterior tooth, received an inferior alveolar nerve block and had
      moderate to severe pain upon endodontic access. A computer-controlled local
      anesthetic delivery system was then used to administer intraligamentary
      injections of 1.4 ml of 2% lidocaine with 1:100,000 epinephrine. Success of the
      intraligamentary injection was defined as none or mild pain upon endodontic
      access or initial instrumentation. The results demonstrated that anesthetic
      success was obtained in 56% (30 of 54) of the patients. We concluded that when
      the inferior alveolar nerve block failed to provide profound pulpal anesthesia in
      mandibular posterior teeth of patients presenting with irreversible pulpitis, the
      intraligamentary injection administered with a computer-controlled local
      anesthetic delivery system was successful approximately 56% of the time.

PMID- 15851929
TI  - Reduction of intracanal bacteria using GT rotary instrumentation, 5.25% NaOCl,
      EDTA, and Ca(OH)2.
AB  - This study was conducted to determine the bacterial reduction using Profile GT
      files and a strict irrigation protocol utilizing 5.25% NaOCl and EDTA. The
      additive antibacterial effect of Ca(OH)2 was also evaluated. In addition, the
      study compared the bacterial reduction with the GT protocol versus larger
      instrumentation. Thirty-one subjects with apical periodontitis were recruited.
      Bacterial samples were taken upon access (S1), after instrumentation and a strict
      irrigation protocol (S2), and following >1 wk of Ca(OH)2 (SC). A log10
      transformation of colony forming units was done since sample bacterial counts are
      not normally distributed. At S1, 93.55% of canals sampled bacteria. At S2, 52.72%
      of the cases sampled bacteria. At SC, 14% of the cases cultured bacteria. The
      McNemar test showed a significant reduction (p<0.0009) in bacteria between S1 and
      S2. This was also true between S2 and SC (p<0.0019). It was concluded the GT
      protocol significantly reduced the number of bacteria in the canal but failed to
      render the canal bacteria free in more than half of the cases Ca(OH)2 application
      significantly further reduced bacteria. Lastly, large apical instrumentation
      removed more bacteria than small apical instrumentation.

PMID- 15851930
TI  - Apical anatomy in mesial and mesiobuccal roots of permanent first molars.
AB  - The purpose of this in vitro study was to investigate the canal configuration
      types, and the prevalence and location of anatomical variations in the
      mesiobuccal (MB) and mesial roots of permanent maxillary and mandibular first
      molars after instrumentation. The number and the type of canals were determined
      before instrumentation using conventional methods. All root canals from the 47 MB
      roots and 42 mesial roots were then instrumented to size #30 with ProFile .04
      taper rotary instruments in a crown-down method and then filled with a single
      gutta-percha cone and sealer. Transverse 1 mm-thick cross-sections at 2, 3, 4,
      and 5 mm from the apex were obtained, stained and examined using a
      stereomicroscope. The canal configuration types and the prevalence and location
      of isthmi and accessory canals in roots with two canals were evaluated. The
      prevalence of two canals was 80.8% in the maxillary MB roots and 95.2% in the
      mandibular mesial roots. There were six types of canal configurations in the
      instrumented root apices. The prevalence of anatomical variations was highest at
      the apical 4 mm level, and was more frequent in mandibular first molars, and in
      roots with Weine type III canal. chi test showed that the prevalence of the
      anatomical variations was statistically higher in the maxillary MB roots with
      Weine type III canals than in those with Weine type II canals (p < 0.05).
      Different canal configurations were often found at different levels in the same
      root. The results indicate that anatomical variations persist following
      instrumentation of roots with two canals in first molars. These anatomical
      variations should be considered during surgical or nonsurgical endodontic
      procedures of the permanent first molars.

PMID- 15851931
TI  - The expression of alpha4 integrins by human polymorphonuclear neutrophils in
      response to sonicated extracts of Enterococcus faecalis.
AB  - This study was undertaken to investigate immunopathologic mechanism of
      Enterococcus faecalis in relation to persistent apical periodontitis. We
      monitored the expression levels of alpha4 integrin in human polymorphonuclear
      neutophils (PMNs) after stimulated with sonicated extracts of E. faecalis (SEF)
      and compared with lipopolycaccarides (LPS) of Escherichia coli for various
      incubation time. Venous blood was collected from healthy volunteers and then PMNs
      were isolated and cultured with various concentrations of SEF for different
      periods of time. The levels of alpha4 integrin were measured by flow cytometry
      analysis. E. coli LPS group was used as a positive control and untreated PMNs as
      a negative control. Results showed that the expressions levels of alpha4 integrin
      were increased in human PMNs stimulated with E. coli LPS in comparison with
      unstimulated control cells (p < 0.05). In case of SEF stimulated group, the
      expression levels were decreased in time-dependent manner in comparison to E.
      coli LPS group (p < 0.05). Notably, after 12 h for incubation with SEF, the
      expression of alpha4 integrin was decreased in dose-dependent manner (p < 0.05).
      These findings suggest that E. faecalis seem to suppress PMNs recruiting activity
      by down-regulating alpha4 integrin expression, providing the possible mechanism
      that E. faecalis may play a crucial role in persistent apical periodontitis.

PMID- 15851932
TI  - The shaping effects of three nickel-titanium rotary instruments in simulated S
      shaped canals.
AB  - The purpose of this study was to compare the shaping effects of three nickel
      titanium rotary instruments, ProTaper, K3, and RaCe, with emphasis on canal
      transportation. Simulated canals with an S-shaped curvature in clear resin blocks
      were prepared with a torque-control, low-speed engine. Canals were prepared using
      the crown-down technique to the size of #30. Canal aberrations were assessed by
      comparing the pre- and postinstrumentation images under a stereomicroscope.
      ProTaper instruments caused greater widening of canals compared to K3 or RaCe.
      Furthermore, ProTaper files showed a tendency to ledge or zip formation at the
      end-point of preparation. These canal aberrations may be caused by ProTaper
      finishing files, which appear to be less flexible than other files of the same
      tip-size, because of their greater taper-size. These results suggest that nickel
      titanium file systems including less tapered, more flexible instruments, like K3
      and RaCe should be used in the apical preparation of canals with a complicated
      curvature.

PMID- 15851933
TI  - MTA solubility: a long term study.
AB  - The purposes of this long-term study was to assess the amount of soluble material
      released by Mineral Trioxide Aggregate to a water medium, to determine if the
      solubility differences between specimens of various water/powder ratio, as
      demonstrated in a previous study, would be maintained over time, and to measure
      the pH of the water that was in contact with the specimens. Specimens were
      processed at 0.28 and 0.33 water/powder ratios, and immersed in water according
      to the ISO 6876 standard. The specimens were periodically removed to assess salt
      content release and reimmersed in fresh water. Assay testing was periodically
      performed over a 78-day period. Results were expressed as Daily Solubility
      (solubility rate), and Cumulative Solubility. The mathematical projection from
      Cumulative Solubility to infinite time showed that MTA could solubilize 22.06% at
      0.28 water/powder ratio, and 31.095% at 0.33 water/powder ratio of the specimens'
      mass in regards to their initial dry weight. MTA did maintain a high pH for an
      extended period of time under these study conditions.

PMID- 15851934
TI  - The susceptibility of starved, stationary phase, and growing cells of
      Enterococcus faecalis to endodontic medicaments.
AB  - The purpose of this investigation was to compare the susceptibility of cells of
      Enterococcus faecalis during exponential growth, stationary phase and starvation
      phase to three endodontic medicaments. E. faecalis strains VP3-80 and A197A in
      different growth phases were exposed to saturated calcium hydroxide solution,
      0.05% chlorhexidine digluconate and 0.0001% sodium hypochlorite. Cells in the
      exponential growth phase were the most sensitive to all three medicaments and
      were killed between 3 s and 10 min. Cells in stationary phase were more resistant
      and living cells could be recovered at 10 min. However, cells in starvation phase
      were the most resistant and were not totally eliminated by the medicaments during
      the 10-min test period. Number of surviving cells of E. faecalis cells to the
      tested medicaments increased 1000- to 10,000-folds in aging cultures.

PMID- 15851935
TI  - Effect of ProRoot MTA on pulp cell apoptosis and proliferation in vitro.
AB  - ProRoot Mineral Trioxide Aggregate (MTA) has been indicated as a pulp capping
      material. The purpose of this study was to evaluate the effect of tooth-colored
      (white) MTA on pulp cell apoptosis and cell cycle. Mouse odontoblast-like cells
      (MDPC-23) and undifferentiated pulp cells (OD-21) were exposed to 0 to 100 mg MTA
      for 24 h. Propidium iodide staining followed by flow cytometry demonstrated that
      MTA did not induce apoptosis of MDPC-23 or OD-21 (p > 0.05). Cell cycle analysis
      showed that MTA induced a modest (but significant) increase in the percentage of
      MDPC-23 in the S and G2 phases, and OD-21 in the S phase of cell cycle, as
      compared to untreated controls (p </= 0.05). In conclusion, MTA induced
      proliferation, and not apoptosis, of pulp cells in vitro. These findings suggest
      a potential mechanism to explain the regenerative effect observed in the dentin
      pulp complex when MTA was used for direct pulp capping.

PMID- 15851936
TI  - Evaluation of the apical seal in root canals prepared with a new rotary system
      and obturated with a methacrylate based endodontic sealer: an in vitro study.
AB  - The purpose of this study was to evaluate in vitro the apical seal of root canals
      prepared with a new rotary system, Anatomic Endodontic Technology (AET) and
      filled with a methacrylate based endodontic sealer and a single gutta-percha cone
      and a lateral condensation technique, using the methacrylate based endodontic
      sealer/filler or Grossman's cement. The root canals of 45 freshly extracted human
      maxillary anterior teeth were prepared and then randomly assigned to three groups
      of 15 teeth each. After cleaning and shaping the teeth were obturated as follows:
      in group 1 the canals were filled with a methacrylate based sealer and a single
      gutta-percha cone; in group 2 the canals were filled using a lateral condensation
      technique with gutta-percha and the methacrylate based sealer; and in group 3,
      the canals were filled by means of lateral condensation of gutta-percha and
      Grossman's cement (control group). The specimens were stored in 100% relative
      humidity at 37 degrees C for 72 h, after which the coronal portion and the root
      surface of each tooth was covered with three layers of nail varnish and a final
      layer of sticky wax. After immersion in 2% methylene blue dye for 7 days, the
      specimens were imbedded in clear orthodontic resin and sectioned. Dye penetration
      was evaluated by an independent investigator using a stereo microscope. The
      results demonstrated that more pronounced leakage occurred in root canals
      obturated with the lateral condensation technique and Grossman's cement (p <
      0.05). The least amount of dye leakage was observed for group 1 and 2 in which
      the methacrylate based sealer was used, either with a single gutta-percha cone or
      with lateral condensation of gutta-percha.

PMID- 15851937
TI  - Selective influence of dentin thickness upon cytotoxicity of dentin contacting
      materials.
AB  - The effect of three dentin contacting materials on three-dimensional cultures of
      pulp-derived cells was evaluated in a dentin barrier test device. The test
      materials (Syntac Classic, Prompt L-Pop, Vitrebond) were applied on dentin disks
      of different thicknesses ranging from 100 to 500 microm. After 24 h of exposure
      with and without perfusion of the test chamber, cell survival was evaluated using
      the MTT assay and related to a nontoxic control material. Syntac Classic
      decreased cell activity significantly (p </= 0.0003), independently of the dentin
      thickness. For Prompt L-Pop and Vitrebond a significant influence of dentin
      thickness was found on the cell reaction. After exposure of the control material,
      photometric readings showed no dependency of the cellular reaction on dentin
      thickness (p > 0.05). It could be demonstrated that dentin acts as a barrier,
      decreasing the elicited cytotoxicity with increasing thickness. This effect is
      material related, showing little influence for the nontoxic or the glutaraldehyde
      containing material.

PMID- 15851938
TI  - Three canals in the mesiobuccal root of a maxillary first molar: a case report.
AB  - This article describes the identification and treatment of a maxillary first
      molar exhibiting three canals in the mesiobuccal root. An 18-yr-old male patient
      presented for nonsurgical root canal therapy of tooth #3. After accessing the
      pulp chamber, and probing with 2.5x magnification, only one canal was located in
      the mesiobuccal root initially. Subsequent to troughing the groove between the
      mesiobuccal and palatal canals with a #2 round bur, two additional canals were
      located. An electronic apex locator was utilized to ensure a perforation of the
      pulpal floor had not occurred. A working film confirmed the presence of three
      canals in the mesiobuccal root, and the canals were cleaned, shaped, and
      obturated.

PMID- 15851940
TI  - [Idiopathic sudden sensorineural hearing loss: a review].
AB  - Idiopathic Sudden Sensorineural Hearing Loss (ISSHL) remains one of the major
      unsolved otologic emergencies. It is characterized by the onset of an unilateral
      sensorineural hearing loss developing within 24 hours, and averaging on pure tone
      audiogram at least 30 dB HL for three subsequent octave steps, with no marked
      vestibular symptoms and no identifiable cause. ISSHL is a syndrome covering
      several heterogeneous entities resulting from different pathogenetic mechanisms.
      At this time, the audiogram is the unique tool which may help clinicians to
      identify these entities and provide a classification based on 5 types of hearing
      loss. Numerous experimental and clinical studies have investigated the mechanisms
      by which infectious, ischemic, mechanic or immunologic insults may induce
      cochlear dysfunction. However, extrapolation to humans and rationale therapeutic
      approaches to ISSHL remain uncertain. SSHL being a diagnosis of exclusion,
      retrocochlear and neurologic etiologies should be eliminated. No argument allows
      to consider ISSHL a therapeutic emergency. More precisely, the experimental data
      presently available on cochlear physiology suggests that a treatment could have
      some chance to be effective if undertaken within minutes following the onset of
      ISSHL, a condition never encountered in daily practice. Conversely, it is not
      justifiable to impute the absence of hearing recovery to a delay in therapy. The
      various therapeutic strategies currently recommended are highly empirical and
      should be questionned in terms of cost-effectiveness, the most common being high
      dose corticosteroids. New investigation tests are required for improving our
      approach to ISSHL.

PMID- 15851941
TI  - [Secondary malignant tumors of the parotid].
AB  - AIM OF THE STUDY: Secondary malignant tumors of the parotid gland are uncommon.
      They arise from primary tumors located in the head and neck or from distant
      primary tumors. The formers are dominated by squamous cell carcinomas and
      melanomas, the latters by renal and lung cancers. Distinction between malignant
      primary tumors and metastasis of other primary tumors to the parotid gland is
      very important to appreciate, because the result of this will change therapeutic
      procedure and the evaluation of prognosis. METHODS: A series of 23 patients with
      tumors metastatic to the parotid gland are reported. All clinical and
      pathological data were reviewed. The management of secondary tumors of the
      parotid gland and the results were analyzed in order to try to identify common
      features and implications for management. RESULTS: The most frequent histologic
      types were squamous cell carcinoma and melanoma. Most primary tumors occurred in
      the head and neck. Metastasis to the parotid gland presented with a median time
      of 18 months after diagnosis of the primary tumor. All the patients had a parotid
      mass. No patient had facial nerve weakness. Parotid metastases were treated by
      superficial parotidectomy with preservation of the facial nerve in all cases,
      associated in 14 cases with a homolateral selective neck dissection and in 6
      cases with a homolateral radical neck dissection. Twenty-one patients were
      submitted to radiation therapy. Seven patients died after the treatment: in 3
      cases, death was due to a local recurrence with cervical relapse; 4 patients
      presented cervical and metastatic lesions. CONCLUSION: This retrospective review
      confirmed that patients with involvement of cervical nodes and metastatic parotid
      tumors have a worse prognosis than those without involvement of cervical nodes.
      The addition of postoperative radiotherapy provides no additional benefit.

PMID- 15851942
TI  - [Treatment of simple snoring by radiofrequency velar coblation].
AB  - OBJECTIVES: Short- and long-term evaluation of the efficacy and safety of
      radiofrequency velar coblation for simple snoring. MATERIAL AND METHODS: From
      February 2000 to May 2004, 175 patients underwent a single radiofrequency session
      for velar coblation. All patients suffered from snoring without sleep apnea. They
      presented modifications of the velo-pharyngeal region but did not have tonsillar
      or basilingual hypertrophy. Outcome was assessed in terms of pain, changes in
      snoring, secondary effects and complications at three months and one, two, and
      three years. Secondary uvulectomy was performed in 28 patients. RESULTS: At three
      months, snoring had decreased in 82% of patients with complete resolution in 12%.
      Outcome remained unchanged in 70% of patients at one, two, and three years. After
      uvulectomy, snoring declined in 96% of patients with complete resolution in 48%.
      Post-treatment pain lasted less than five days in 68% of patients. Mean duration
      was three days. Fifteen patients developed pharyngeal paresthesia which regressed
      at one year. Two patients had a nasal voice and three developed necrosis of the
      uvula. CONCLUSION: Velar coblation is a simple treatment for snoring which can be
      performed in a single session. The best results are achieved in patients whose
      body mass index is below 25 and after secondary uvulectomy.

PMID- 15851943
TI  - [Surgical treatment of malignant sinonasal tumors with orbital extension: 20
      patients].
AB  - OBJECTIVE: The purpose of this work was to assess changes in surgical treatment
      of malignant sinonasal tumors with orbital extension, with or without orbital
      exenteration, on the basis of clinical, radiological and preoperative data.
      MATERIAL AND METHODS: We conducted a retrospective analysis of twenty patients
      with malignant sinonasal tumors with orbital extension operated on from 1995 to
      2002 in the ENT and head and neck department of the Strasbourg University
      Hospital. CT-scan and MRI were performed before surgery. When periorbital
      invasion was observed without orbital extension and confirmed by histological
      examination in the operative theatre, the orbit was preserved during the surgical
      procedure. Orbital exenteration was necessary for the other patients. Adjunct
      postoperative radiotherapy was performed in all patients (n=20). Clinical,
      radiological and surgical data were compared with patient follow-up to search for
      correlations between radiological signs and the difficult surgical decision for
      orbital exenteration. RESULTS: For orbital extension, the histological
      examination performed in the operative theatre did not confirm the results of the
      preoperative CT-scan in 15% of patients and the preoperative MRI in 11%. In a
      first group of nine patients with bony wall extension (78%, 7/9) or periorbital
      extension (22%, 2/9), there were no cases of recurrence at six years follow-up.
      In a second group of eleven patients with intraorbital extension, orbital
      exenteration was not performed in two (18%) because of surgically unresectable
      massive extension. Four of the nine other patients who underwent orbital
      exenteration were free of local recurrence at ten months follow-up and five were
      considered to have achieved oncological cure at four years follow-up. CONCLUSION:
      Preoperative CT and MRI are essential but the decision for orbital exenteration
      must be made on the basis of the histological examination performed during the
      operative procedure because imaging often underestimates tumor extension.

PMID- 15851944
TI  - [Contribution of computed tomography in experimental sinus surgery].
AB  - OBJECTIVES: To study the contribution of computed tomography (CT) to evaluate the
      intensity of the sinus mucosa's response to an inflammatory stimulus. MATERIAL
      AND METHODS: Eight New-Zealand white rabbits where used. Rabbit n degrees 1 was
      the control. CT, macroscopic examination with analysis of secretion volumes, and
      histological examination were used to study the response of the sinuses to
      inflammation. RESULTS: There was perfect match between the CT scan aspect and the
      quantity of secretions (kappa and Cohen's coefficient=1). The CT scan aspect well
      correlated with inflammatory cell infiltration (kappa and Cohen's
      coefficients=0.8). CONCLUSION: The CT scan contributes usefully to the analysis
      of sinus contents and can be used to assess the intensity of the sinus mucosal
      inflammatory reaction. Consequently, the CT scan can be used not only to validate
      an animal model of acute or chronic sinusitis, but can also be used to evaluate
      medical or surgical treatments in such an animal model.

PMID- 15851946
TI  - [Local antibiotic therapy in ENT patients].

PMID- 15851947
TI  - [Postoperative acute endophthalmitis: a prospective study. Clinical presentation,
      management and prognostic factors].
AB  - AIMS: To assess the characteristics and visual outcome of patients with acute
      postoperative endophthalmitis hospitalized in a referral center. MATERIALS AND
      METHODS: All patients suspected of having infectious endophthalmitis were
      included in this study. All patients were treated with the same protocol
      including at least intravitreal injection of antibiotics and instillation of
      fortified antibiotics. Symptoms, visual acuity, and slit lamp examination were
      recorded before treatment, at the end of hospitalization and during clinical
      follow-up. Treatments and biological results were also reported. For patients
      developing infectious endophthalmitis after cataract surgery, intraoperative
      management such as location of the incision, suture or sutureless incision, and
      material of the intraocular lens were also noted. RESULTS: Forty-one patients
      were included in the study over 32 months (33 patients after cataract surgery).
      Intraocular inflammation and a decrease in subjective visual acuity were the most
      frequently reported findings (90% and 94%, respectively). Ocular pain and
      conjunctiva injection were less frequently reported (47% and 48%, respectively).
      Symptoms occurred 5 days after the surgery (median); 56% of patients needed a
      second intravitreal injection of antibiotics. There was a significant increase in
      visual acuity during and after hospitalization; median final visual acuity was
      4.6/10 (0.34 log MAR = 20/43); 30% of patients had less than 20/200, but 44% more
      than 20/40. In endophthalmitis following cataract surgery, incisions were corneal
      in all cases and sutured in 62% of cases. Incisions were temporal in 55% of
      patients. DISCUSSION: Our results are similar to those previously published for
      acute endophthalmitis following ocular surgery. Intravitreal antibiotic injection
      remains the gold standard on the management of acute postoperative
      endophthalmitis.

PMID- 15851948
TI  - [Postoperative endophthalmitis: 2000-2002 results in the XV-XX National
      Ophthalmologic Hospital].
AB  - PURPOSE: Prevention of nosocomial infection is a priority for the Infection
      Control Committee (ICC). Following their recommendations, the XV-XX National
      Ophthalmologic Hospital's ICC conducted a survey on cases of infection and we
      report these results for the 2000-2002 period. METHODS: During the 2000-2002
      period, 21,384 programmed intraocular surgeries were done. Every day, a hygiene
      coordinator was informed of each bacterial or fungal laboratory test on
      intraocular samples and for all patients who were hospitalized for
      endophthalmitis. After data analysis with a referent ICC physician, resulting
      infection was declared postoperative nosocomial endophthalmitis. For these
      patients, prophylactic antibiotic use, the surgery report, and bacterial
      laboratory test results were reviewed. RESULTS: The overall 3-year incidence of
      suspected postoperative endophthalmitis after intraocular surgery was 2.0 per
      1000 (42 cases). Confirmed microbiological growth was demonstrated in 19 cases
      (45%). For cataract surgery, the incidence was 1.0 per 1000 for acute-onset
      culture-proven postoperative endophthalmitis, 0.1 per 1000 for delayed culture
      proven postoperative endophthalmitis, 2.1 per 1000 for acute-onset suspected
      postoperative endophthalmitis and 0.5 per 1000 for delayed suspected
      postoperative endophthalmitis. Gram-positive cocci were isolated in 77%. Twenty
      one patients received systemic prophylactic antibiotics. Bacterial growth was
      positive in five of these 21 cases. For two cases, organisms were resistant to
      the prophylactic antibiotics used. CONCLUSION: Monitoring postoperative
      nosocomial infection is mandatory to detect incidence variation and evaluate
      infection control management. Prophylactic antibiotic efficacy remains to be
      evaluated.

PMID- 15851949
TI  - [Ultrastructural study of epiretinal membrane stained by trypan blue: 15 case
      reports].
AB  - INTRODUCTION: Idiopathic epiretinal membrane results from detachment of the
      posterior hyaloid and is believed to be related to naturally occurring defects in
      the internal limiting membrane (ILM) of the retina. Vitrectomy and peeling are
      the treatment of choice. Trypan blue 0.15% (TB) stains epiretinal membrane and
      internal limiting membrane. It allows selective and complete removal,
      facilitating surgery, with less retinal damage. An ultrastructural study was
      conducted showing ultrastructural features of idiopathic epiretinal membranes
      (ERM) and those of the internal limiting membrane and its connections with the
      retinal side. MATERIAL AND METHODS: After pars plana vitrectomy and induction of
      posterior vitreous detachment, 0.2 ml TB 0.15% was injected over the ERM in an
      air-filled eye. The stained tissue was peeled with intraocular forceps. Specimens
      were at once collected in 4% glutaraldehyde for a transmission electron
      microscopy study. RESULTS: TB may allow complete and easier ERM and ILM peeling.
      The staining does not present toxic effects. The major cellular contingent is
      represented by glial cells, participating actively in neocollagen synthesis.
      Their presence supports the hypothesis of a migratory movement of retinal cells
      toward the vitreoretinal side. CONCLUSION: The presence of an intact internal
      limiting membrane, the absence of optical fibers belonging to the under retina,
      and the absence of any sign of apoptosis make TB a useful staining agent for ERM
      and ILM peeling.

PMID- 15851950
TI  - [Evaluation of trypan blue toxicity in idiopathic epiretinal membrane surgery
      with macular function test using multifocal electroretinography: seven
      prospective case studies].
AB  - INTRODUCTION: Idiopathic epiretinal membranes are considered the consequence of
      glial proliferation through a defect of the internal limiting membrane and can
      induce a functional macular syndrome associating mainly metamorphopsia and visual
      acuteness. Visual disturbance is not bound to the area and the degree of
      transparency of the membrane, but to distortion of external layers of the retina.
      Multifocal electroretinography (ERGm) can assess the macular area and retina
      extending 20 degrees. We used this tool to study macular function pre- and post
      operatively with seven patients presenting idiopathic epiretinal membrane.
      PATIENT AND METHOD: All patients had successful vitrectomy, with 0.2 ml of 0.15%
      trypan blue (TB) staining to facilitate peeling. This stain is not toxic for the
      pigment epithelium but it becomes so for photoreceptors at doses exceeding 0.2%.
      We tried to estimate the echo of TB 0.15% on photoreceptors through this exam. An
      ERGm was done 1 week before the operation as well as 1 month and 4 months after
      on 14 eyes of seven patients with ERMs. RESULTS: Results show a pre-operative
      decrease in the electrical retinal response densities in the foveal, perifoveal
      and parafoveal areas. One month after operation, no significant difference was
      found compared to pre-operative results. However, at 4 months, an improvement of
      the retinal response density was observed. Retinal response densities in the
      macular area increased progressively after ERM surgery. CONCLUSION: The 0.15% TB
      facilitated ERM peeling and does not seem to present any retinal toxicity.

PMID- 15851951
TI  - [Diagnostic laser in glaucoma: scanning laser polarimetry (GDx VCC) and confocal
      scanning laser tomography (HRT)].
AB  - Automated structural measurements of retinal nerve fibers and optic nerve head
      are possible with new lasers providing objective and reproductible data for
      analysis. Scanning laser polarimetry (GDx VCC), based on retardation of polarized
      light, assesses peripapillary nerve fiber layer thickness. Confocal scanning
      laser tomography yields precise topographic maps of the optic disc and
      peripapillary retina. The advantages, applications for glaucoma detection, both
      in a screening setting as well as for monitoring progression, limitations and
      pitfalls need to be well known and results should be analyzed with clinical data.

PMID- 15851952
TI  - [Three conventional eye drops versus a single lyophilisate. A comparative
      bioavailability study].
AB  - PURPOSE: The ocular bioavailability of a single application of a triple dose of
      sodium fluorescein to the human anterior segment of the eye was studied as a
      novel drug delivery device. METHODS: The lyophilisate contained a fluorescein
      dose of 204 microg corresponding to three conventional, preservative-free eye
      drops of 40 microl Fluorescein SE Thilo 0.17% (68microg each) (Alcon). A single
      lyophilisate was applied to one eye of 22 healthy volunteers (+1 min) and three
      conventional eye drops (+1, 16, 31 min) were applied to their fellow eye. In this
      randomized, open label study, fluorophotometry was performed (Fluorotron Master
      IItrade mark, Ocumetrics, Mountain View, California, USA) before and +15, 30, 45,
      60, 120, 180, 240, 300, 360, 420 min after application. The fluorescein
      concentrations of the corneal stroma (C), mid-anterior chamber (AC) were analyzed
      by paired t-test. RESULTS: Cornea and AC mean values (ng/ml) were significantly
      higher (p < 0.018, paired t-test) in the lyophilisate group up to 7 h after
      application, with the exception of +45 min. The mean fluorescein bioavailability
      from the lyophilisate was up to 11 times higher in the C and up to 8.7 times
      higher in the AC compared with the three preservative-free eye drops. DISCUSSION:
      For the first time a triple dose was delivered to the human eye with a single
      lyophilisate application. Significantly better bioavailability was achieved in
      the C and AC for up to 7 h using this new device. The treatment of glaucoma,
      bacterial, viral, and fungal infections, as well as dry eye syndrome, for
      example, will be improved using lyophilisate.

PMID- 15851953
TI  - [Nonpenetrating deep sclerectomy in Brazil: a 3-year retrospective study].
AB  - INTRODUCTION: Nonpenetrating deep sclerectomy with external trabeculectomy has
      been proved to be an effective alternative to classic trabeculectomy for surgical
      treatment of primary open-angle glaucoma. However, this procedure is not well
      known nor well accepted among Brazilian ophthalmic surgeons. The aim of this
      study was to assess the results and success rate of this new filtering surgical
      procedure in a Brazilian population, with a 3-year follow-up. METHOD: One-hundred
      eleven primary open-angle glaucoma patients underwent deep sclerectomy with
      external trabeculectomy between 1999 and 2002 (the surgery was performed by two
      different surgeons using the same procedure). The antimetabolite mitomycin C (0.2
      mg/ml) was applied intraoperatively in 80 patients with high surgical risk of
      failure (80 patients under 45 years of age, black, and having had previous ocular
      surgery). The postoperative follow-up included assessment of visual acuity,
      measure of intraocular pressure (IOP), evaluation of the filtration site and
      optic nerve head using biomicroscopy, and analysis of visual field deficits.
      Complete success was defined as IOP less than 18 mmHg without medical treatment,
      while relative success was defined as IOP less than 18 mmHg with medical
      treatment. RESULT: The mean age was 63.7 +/- 13.1 years and 42.3% of patients
      were black. Mean follow-up was 19.4 months (+/- 11.7). The mean preoperative
      intraocular pressure was 22.57 +/- 4.92 mmHg, while mean IOP at the last follow
      up visit was 14.22 +/- 2.89 mmHg, so that at the end of the follow-up, complete
      success was 82.7% and relative success was 93.3%. The cumulative probability of
      complete success was 76% at 3 years. The complication rate was low:
      intraoperative microperforations (14.4%), conjunctival seidel (12.5%), hyphema
      (3.8%), flat anterior chamber (2.9%), choroidal detachment (1%), and filtering
      bleb fibrosis (17.3%). DISCUSSION AND CONCLUSION: These results demonstrate that
      deep nonpenetrating sclerectomy with external trabeculectomy is a safe and
      efficient filtering procedure that provides satisfactory IOP control with a
      minimal rate of complications, even in patients with high surgical risk of
      failure such as the highly mixed Brazilian population. The results suggest that
      this revolutionary procedure could be used as first-intention treatment in
      Brazilian glaucomatous patients that do not have access to expensive medical
      treatment.

PMID- 15851954
TI  - [T-cell acute lymphoblastic leukemia /orbital lymphoblastic lymphoma in
      children].
AB  - CASE: The authors report a case of an 6-year-old pediatric patient with a history
      of acute onset of proptosis of his right eye. He was admitted at hospital 6
      months ago for proptosis concomitant with orbital trauma. Computed tomography
      scan demonstrated a mass involving the right orbit, right maxillary sinus, and
      zygoma with endocranial extension. RESULTS: Incisional biopsy of the mass
      revealed after of histopathologic and immuno-histochemical evaluation a T-cell
      lymphoblastic lymphoma. Systemic examination and bone marrow aspirate show a
      acute lymphoblastic leukemia. The patient was treated with LMT96 Protocol. A
      complete Remission was observed after 13 months of follow up. CONCLUSION: Primary
      T-cell lymphoblastic lymphoma of the orbit is a rare entity in any age group, but
      it is very rare in children. When tumors occurs in the orbit, it presents a
      challenging diagnosis problem, especially in pediatric patients.

PMID- 15851955
TI  - [Optic neuritis associated with infliximab].
AB  - Infliximab is a chimeric human-murine monoclonal antibody of the IgG1 type with a
      high affinity and specificity for tumor necrosis factor alpha (TNFalpha).
      Infliximab was used in Crohn disease, rheumatoid arthritis, spondyloarthropathy,
      juvenile idiopathic arthritis, Behcet's disease, Wegener's granulomatosis, HLA
      B27-associated uveitis and chronic severe refractory uveitis. Reported adverse
      effects of this treatment were infections, development of antinuclear antibodies
      and anti double-stranded DNA, lymphomas, and exacerbation of demyelinating
      disease. We report a case of infliximab-associated optic neuritis with favorable
      outcome after systemic steroid treatment.

PMID- 15851956
TI  - [Keratoconus: current surgical options].
AB  - The treatment of keratoconus is in part dependant on the severity of the disease
      process. When contact lenses fail because of patient intolerance or insufficient
      acuity to meet the patient's needs, penetrating keratoplasty is the usual
      surgical modality considered for satisfactory visual rehabilitation. Keratoconus
      is considered to be a contraindication for incisional refractive surgery such as
      radial keratotomies or LASIK because of the corneal instability conferred by
      these procedures. When the cornea is transparent, INTACS implantation is a
      refractive modality that may improve visual function and in some instances
      prevent the need for corneal transplantation in select patients with keratoconus.

PMID- 15851957
TI  - [Lyme disease from an ophthalmological point of view].
AB  - The first case of Lyme disease was described more than 25 years ago in the city
      of Lyme, Connecticut (USA) and although the responsible pathogenic organism is
      known (Borrelia Burgdorferi) as well as its vector (a tick from the Ixode genus),
      it is still underdiagnosed and often poorly known by practitioners. The
      symptomatology is classically divided into three phases depending on the time
      between the tick bite and the first symptoms. However, in a number of cases this
      clinical division of the disease is not easily applied. We describe three cases
      of atypical ocular manifestations to illustrate this problem. Recently developed
      laboratory tests help confirm the diagnosis but should not be used without a good
      knowledge of the disease. This study aims to emphasize the difficulty of
      diagnosis and the importance of appropriate treatment and to avoid potentially
      permanent complications.

PMID- 15851958
TI  - [Staphylococcus epidermidis biofilms on intraocular lens surface: review of the
      literature].
AB  - Bacterial adhesion to intraocular lenses (IOLs) takes place during their
      implantation. This is a prominent etiological factor of postoperative
      endophthalmitis. Following adhesion, secretion of an extracellular matrix (called
      slime for Staphylococcus epidermidis) and formation of multiple layers of
      microcolonies lead to the colonization of the biomaterial surface. Scanning
      electron microscopy photographs illustrate the different steps of biofilm
      formation. The different adhesins expressed by S. epidermidis involved in the
      adhesion process are described. The biofilm is not only an adhesive medium; it
      also affects virulence. Last, notions on biofilm physiology are discussed in an
      attempt to explain the dynamic equilibrium of this system. In 2004, the perfect
      biomaterial able to prevent postoperative endophthalmitis does not yet exist.
      Moreover, there is no effective tool, at the present time, to fight against
      mature biofilms. Therefore, preventing biofilm formation remains capital, which
      requires perfect knowledge of all stages of formation and the factors involved.

PMID- 15851960
TI  - [Cerebral cavernomas, epilepsy and seizures. Natural history and therapeutic
      strategy].
AB  - PURPOSE: To review, from a retrospective series of 48 patients presenting with
      seizures associated with one or more supratentorial cavernoma(s), the natural
      history of the seizures and outcome according to medical and surgical treatment.
      METHODS: Patients were divided into two groups: group A included patients
      presenting with a single seizure or rare seizures (n=21), and group B patients
      having intractable epilepsy (n=27). All received antiepileptic drugs and 35 were
      operated on (12 in the group A and 23 in the group B). Stereo-EEG was performed
      in 8 patients in group B. Surgery included lesionectomy alone (n=16), resection
      of the cavernoma and perilesional tissue (n=7) or tailored corticectomy including
      the cavernoma (n=12). RESULTS: The natural history of seizures was different in
      the two groups: mean age at seizure onset was 25 years in group B and 33 years in
      group A (p<0.05), seizures were partial in all patients in group B and 8 patients
      in group A (p<0.05). Seizure frequency and periodicity also varied. Prolonged
      seizure-free periods were observed. The cavernoma was temporal in 17 patients in
      group B and 4 patients in group A (p<0.01). In group A, seizure outcome was
      favorable following surgery or with antiepileptic medication only (7 patients out
      of 12 operated were seizure-free, as were 5 out of 7 non-operated). In group B,
      seizure outcome was better after surgery than with medication only (17 patients
      out of 23 operated were in Engel's Class I, while 3 patients of 4 non-operated
      patients had persisting seizures despite antiepileptic polytherapy). CONCLUSION:
      Variations in seizure severity in patients harboring cavernomas suggest different
      therapeutic approaches. In case of unique or rare seizures, surgical resection of
      the cavernoma is appropriate, but benefits of surgery over antiepileptic
      medication in terms of seizure control remains unclear. Intractable epilepsy
      associated with cavernomas is better controlled after surgery rather than with
      medication only. In these patients, a detailed preoperative work-up is necessary
      and should be followed by wide resection associated or not with corticectomy,
      especially in the temporal lobe. Evaluation of outcome after surgery should
      consider the surgical strategy, antiepileptic medications and the patient's
      seizure history.

PMID- 15851961
TI  - [Surgical management of cervical radiculopathy in Forestier's disease. Case
      report and review].
AB  - Forestier's disease now called DISH (diffuse idiopathic skeletal hyperostosis) is
      a non inflammatory enthesopathy ossifying the anterolateral spine and sparing the
      disc and joint space in elderly men, mostly at thoracic levels. Radiology
      performed for minor trauma or to explore a stiff neck provides the diagnosis. The
      main differential diagnosis is ankylosing spondylitis presenting an inflammatory
      profile as well as previously existing alterations of the sacroiliac joint.
      Retinoic acid treatment or ossification of the posterior longitudinal ligament
      should also be discussed. Dysphagia is the most frequent symptom, but
      neurological signs are rarely observed. We report a case observed at the cervical
      level. Anterior decompression and cage-fusion was indicated. Ongoing hyperostosis
      was also documented. Surgery in DISH is mainly indicated for dysphagia and rarely
      after cervical trauma. Of note are associated lesions such as OPLL (ossification
      of the posterior longitudinal ligament) or synovial cysts responsible for the
      exceptional and severe myelopathy presentation. The neurosurgical community
      should become better aware of Forestier's disease.

PMID- 15851962
TI  - [Intramedullary schwannoma. A case report].
AB  - The intramedullary localization of schwannoma is rare, corresponding to 0.3% of
      all intraspinal tumors. We report a case of intramedullary schwannoma without
      symptoms suggestive of neurofibromatosis. This patient presented with symptoms of
      spinal compression. Total removal of the tumor was achieved. The literature is
      reviewed about of this rare localization of schwannoma.

PMID- 15851963
TI  - [Temporary vessel occlusion].
AB  - In many situations, temporary artery occlusion is an integral component of
      aneurysm surgery. The use of temporary clip may allow safer and easier aneurysmal
      dissection and clipping. Several points, concerning the duration and overall
      risks of temporary occlusion and the method of choice for cerebral function
      monitoring have to be discussed. MATERIAL AND METHODS: Non exhaustive review of
      neurosurgical literature. DISCUSSION: Temporary clip application decreases the
      risk of intraoperative aneurysmal rupture. The analysis of data published in the
      literature showed that several questions remain open concerning the optimal
      method of neuroprotection and cerebral function monitoring, as well as the limit
      of occlusion duration. Other clinical trials are needed to assess the efficacy
      and safety of this technique.

PMID- 15851964
TI  - [Chronic hydrocephalus in adults: where is the concept in 2005].

PMID- 15851966
TI  - [Frontal syndrome of chronic hydrocephalus in adults].

PMID- 15851967
TI  - [Chronic hydrocephalus in adults: early diagnosis means more effective surgical
      treatment].

PMID- 15851968
TI  - [Chronic hydrocephalus in adults: deviation is simple and effective].

PMID- 15851969
TI  - [Relation between neurosurgery and interventional neuroradiology].

PMID- 15851970
TI  - [New developments in the treatment of glioblastoma].

PMID- 15851973
TI  - [Breath and music: control and demand].

PMID- 15851974
TI  - [Express yourself: which are your strategies to control asthma?].

PMID- 15851975
TI  - [What level of demand to control asthma in 2004?].

PMID- 15851977
TI  - Characterization of the Crumbs homolog 2 (CRB2) gene and analysis of its role in
      retinitis pigmentosa and Leber congenital amaurosis.
AB  - PURPOSE: Mutations in the Crumbs homolog 1 (CRB1) gene cause autosomal recessive
      retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). Database searches
      reveal two other Crumbs homologs on chromosomes 9q33.3 and 19p13.3. The purpose
      of this study was to characterize the Crumbs homolog 2 (CRB2) gene on 9q33.3, to
      analyze its expression pattern, and to determine whether mutations in CRB2 are
      associated with RP and LCA. METHODS: The CRB2 mRNA and its expression pattern in
      human tissues were analyzed by reverse transcription-polymerase chain reaction
      (RT-PCR). The cellular expression of Crb2 in the mouse eye was determined by mRNA
      in situ hybridizations. The open reading frame and splice junctions of CRB2 were
      analyzed for mutations by single-strand conformation analysis and direct
      nucleotide sequencing in 85 RP patients and 79 LCA patients. RESULTS: The CRB2
      gene consists of 13 exons and encodes a 1285 amino acid transmembrane protein.
      CRB2 is mainly expressed in retina, brain, and kidney. In mouse retina Crb2
      expression was detected in all cell layers. Mutation analysis of the CRB2 gene
      revealed 11 sequence variants leading to an amino acid substitution. Three of
      them were not identified in control individuals and affect conserved amino acid
      residues. However, the patients that carry these sequence variants do not have a
      second sequence variant on the other allele, excluding autosomal recessive
      inheritance of CRB2 sequence variants as a cause of their disease. CONCLUSIONS:
      This study shows that CRB2 sequence variants are not a common cause of autosomal
      recessive RP and LCA. It is possible that a more complex clinical phenotype is
      associated with the loss or altered function of CRB2 in humans due to its
      expression in tissues other than the retina.

PMID- 15851979
TI  - Prevalence of myocilin and optineurin sequence variants in German normal tension
      glaucoma patients.
AB  - PURPOSE: To determine the prevalence of optineurin (OPTN) and myocilin (MYOC)
      sequence variants in a cohort of German patients with normal tension glaucoma.
      METHODS: All coding exons of the OPTN and MYOC genes were amplified by PCR from
      genomic DNA and subjected to direct DNA sequencing. Analysis of sequence variants
      in controls was done by denaturing high performance liquid chromatography (DHPLC)
      and restriction fragment length polymorphism (RFLP) analysis. RESULTS: Sequence
      variants were identified by DNA sequencing in 10 of 112 cases. The OPTN sequence
      variant M98K was found in seven patients. In addition, two novel sequence
      variants (A336G and A377T) in the OPTN gene were identified that were not present
      in a control group. Mutation screening also identified two potentially pathogenic
      MYOC mutations (T293K and A445V). CONCLUSIONS: The findings in the current study
      provide further evidence that MYOC and OPTN gene variants are rare causes of NTG.

PMID- 15851978
TI  - Identification of global gene expression differences between human lens
      epithelial and cortical fiber cells reveals specific genes and their associated
      pathways important for specialized lens cell functions.
AB  - PURPOSE: In order to identify specific genes that may play important roles in
      maintaining the specialized functions of lens epithelial and fiber cells, we have
      analyzed the global gene expression profiles of these two cell types in the human
      lens. This analysis will also reveal those genes that are exclusively expressed
      in the epithelial and cortical fiber cells and those genes that may play
      important roles in the differentiation of epithelial cells to mature fiber cells.
      METHODS: Oligonucleotide microarray hybridization was used to analyze the
      expression profiles of 22,215 genes between adult (average age greater than 56
      years) human lens epithelial and cortical fiber cells. The expression levels of
      selected genes were further compared by semi-quantitative RT-PCR and selected
      genes were functionally clustered into common categories using the EASE
      bioinformatics software package. RESULTS: Analysis of three separate microarray
      hybridizations revealed 1,196 transcripts that exhibit increased expression and
      1,278 transcripts that exhibit decreased expression at the 2 fold or greater
      level between lens epithelial cells and cortical fiber cells on all three of the
      arrays analyzed. Of these, 222 transcripts exhibited increased expression and 135
      transcripts exhibited decreased expression by an average of 5 fold or greater
      levels on all three arrays. Semi-quantitative RT-PCR analysis of 21 randomly
      selected genes revealed identical expression patterns as those detected by
      microarray hybridization indicating that the microarray data are accurate.
      Functional clustering of the identified gene expression patterns using the EASE
      program revealed a wide variety of biological pathways that exhibited altered
      expression patterns between the two cell types including mRNA processing, cell
      adhesion, cell proliferation, translation, protein folding, oxidative
      phosphorylation, and apoptosis, among others. CONCLUSIONS: These data reveal
      novel and previously identified gene expression differences between lens
      epithelial and cortical fiber cells. The gene expression differences indicate
      distinct pathways and functions important for the specialization of lens
      epithelial and fiber cells and provide insight into potential mechanisms
      important for lens cell differentiation.

PMID- 15851980
TI  - Use of superparamagnetic microbeads in tracking subretinal injections.
AB  - PURPOSE: The purpose of these studies was to develop a method to track
      intraocular injections. METHODS: Retinal pigment epithelial (RPE) cells, purified
      from adult mouse eyes, were incubated with superparamagnetic microbeads
      (Dynabeads, 4.5 microm) coated with bovine serum albumin to verify that they
      could phagocytose the microbeads. For in vivo tracking studies, mice were
      anesthetized and a small incision was made at the pars plana and 2 mul of
      microbeads (around 10(5) microbeads) or RPE that had taken up the microbeads were
      injected into the subretinal space (SRS). Mice were sacrificed at various times
      after injection. The eyes were enucleated, fixed in formalin, and embedded in
      paraffin. Sections were stained with H&E, visualized by light microscopy. Some
      eyes were digested with collagenase and inflammatory cells determined by flow
      cytometry. RESULTS: Cultured adult RPE phagocytosed the magnetic microbeads. One
      day after injection into the SRS, a retinal detachment was observed at the
      injection point and free microbeads were easily detected at this site. One week
      later, the host RPE cells had phagocytized the microbeads and the retina had
      reattached. No inflammatory response was detected in the eyes that were injected
      with microbeads in the SRS at any time examined. Histology showed normal
      morphology of all retinal layers around the injection site. The microbeads
      remained in situ throughout the study. CONCLUSIONS: Protein coated magnetic
      microbeads are non-inflammatory after injection into the SRS. Host RPE cells
      phagocytized the microbeads and the retina maintained a healthy morphology after
      reattachment. This technique proved not only to be a good training tool to
      determine the precise location of injection, but also provided a noninflammatory
      method for long term marking of delivery into the SRS. However, the microbeads
      can not be used as a tracer of injected RPE because the microbeads were readily
      transferred to the endogenous RPE.

PMID- 15851983
TI  - No more sleepless nights.

PMID- 15851984
TI  - The power of suggestion.

PMID- 15851985
TI  - Placeholders: acknowledging somebody special.

PMID- 15851987
TI  - VT or not VT?: determining the mechanism of an arrhythmia.

PMID- 15851990
TI  - Disaster on the rails: training, teamwork & unified command lead to success at
      California multiple-train MCI.

PMID- 15851991
TI  - The new normalcy: the National Incident Management System fully interfaces EMS
      operations in disaster & MCI responses.

PMID- 15851992
TI  - Radiation terrorism: the unthinkable possibility, the ignored reality.

PMID- 15851993
TI  - Heart sounds: do you hear what I see?

PMID- 15851994
TI  - Visually zero in on medical & WMD conditions.

PMID- 15851997
TI  - Getting to the eCore of data success.

PMID- 15851998
TI  - Ad nauseam: a prescription for overuse & overdose.

PMID- 15851999
TI  - End EMS segregation.

PMID- 15852001
TI  - Migration and differentiation of neural precursors derived from human embryonic
      stem cells in the rat brain.
AB  - Human embryonic stem (hES) cells provide a potentially unlimited cell source for
      regenerative medicine. Recently, differentiation strategies were developed to
      direct hES cells towards neural fates in vitro. However, the interaction of hES
      cell progeny with the adult brain environment remains unexplored. Here we report
      that hES cell-derived neural precursors differentiate into neurons, astrocytes
      and oligodendrocytes in the normal and lesioned brain of young adult rats and
      migrate extensively along white matter tracts. The differentiation and migration
      behavior of hES cell progeny was region specific. The hES cell-derived neural
      precursors integrated into the endogenous precursor pool in the subventricular
      zone, a site of persistent neurogenesis. Like adult neural stem cells, hES cell
      derived precursors traveled along the rostral migratory stream to the olfactory
      bulb, where they contributed to neurogenesis. We found no evidence of cell
      fusion, suggesting that hES cell progeny are capable of responding appropriately
      to host cues in the subventricular zone.

PMID- 15852002
TI  - Integrin-independent repression of cadherin transcription by talin during axis
      formation in Drosophila.
AB  - The Drosophila melanogaster anterior-posterior axis becomes polarized early
      during oogenesis by the posterior localization of the oocyte within the egg
      chamber. The invariant position of the oocyte is thought to be driven by an
      upregulation of the adhesion molecule DE-cadherin in the oocyte and the posterior
      somatic follicle cells, providing the first in vivo example of cell sorting that
      is specified by quantitative differences in cell-cell adhesion. However, it has
      remained unclear how DE-cadherin levels are regulated. Here, we show that talin,
      known for its role in linking integrins to the actin cytoskeleton, has the
      unexpected function of specifically inhibiting DE-cadherin transcription.
      Follicle cells that are mutant for talin show a strikingly high level of DE
      cadherin, due to elevated transcription of DE-cadherin. We demonstrate that this
      deregulation of DE-cadherin is sufficient to attract the oocyte to lateral and
      anterior positions. Surprisingly, this function of talin is independent of
      integrins. These results uncover a new role for talin in regulating cadherin
      mediated cell adhesion.

PMID- 15852003
TI  - Odf2-deficient mother centrioles lack distal/subdistal appendages and the ability
      to generate primary cilia.
AB  - Outer dense fibre 2 (Odf2; also known as cenexin) was initially identified as a
      main component of the sperm tail cytoskeleton, but was later shown to be a
      general scaffold protein that is specifically localized at the distal/subdistal
      appendages of mother centrioles. Here we show that Odf2 expression is suppressed
      in mouse F9 cells when both alleles of Odf2 genes are deleted. Unexpectedly, the
      cell cycle of Odf2(-/-) cells does not seem to be affected. Immunofluorescence
      and ultrathin-section electron microscopy reveals that in Odf2(-/-) cells,
      distal/subdistal appendages disappear from mother centrioles, making it difficult
      to distinguish mother from daughter centrioles. In Odf2(-/-) cells, however, the
      formation of primary cilia is completely suppressed, although approximately 25%
      of wild-type F9 cells are ciliated under the steady-state cell cycle. The loss of
      primary cilia in Odf2(-/-) F9 cells can be rescued by exogenous Odf2 expression.
      These findings indicate that Odf2 is indispensable for the formation of
      distal/subdistal appendages and the generation of primary cilia, but not for
      other cell-cycle-related centriolar functions.

PMID- 15852004
TI  - The transcriptional consequences of mutation and natural selection in
      Caenorhabditis elegans.
AB  - The evolutionary importance of gene-expression divergence is unclear: some
      studies suggest that it is an important mechanism for evolution by natural
      selection, whereas others claim that most between-species regulatory changes are
      neutral or nearly neutral. We examined global transcriptional divergence patterns
      in a set of Caenorhabditis elegans mutation-accumulation lines and natural
      isolate lines to provide insights into the evolutionary importance of
      transcriptional variation and to discriminate between the forces of mutation and
      natural selection in shaping the evolution of gene expression. We detected the
      effects of selection on transcriptional divergence patterns and characterized
      them with respect to coexpressed gene sets, chromosomal clustering of expression
      changes and functional gene categories. We directly compared observed
      transcriptional variation patterns in the mutation-accumulation and natural
      isolate lines to a neutral model of transcriptome evolution to show that strong
      stabilizing selection dominates the evolution of transcriptional change for
      thousands of C. elegans expressed sequences.

PMID- 15852005
TI  - Inversin, the gene product mutated in nephronophthisis type II, functions as a
      molecular switch between Wnt signaling pathways.
AB  - Cystic renal diseases are caused by mutations of proteins that share a unique
      subcellular localization: the primary cilium of tubular epithelial cells.
      Mutations of the ciliary protein inversin cause nephronophthisis type II, an
      autosomal recessive cystic kidney disease characterized by extensive renal cysts,
      situs inversus and renal failure. Here we report that inversin acts as a
      molecular switch between different Wnt signaling cascades. Inversin inhibits the
      canonical Wnt pathway by targeting cytoplasmic dishevelled (Dsh or Dvl1) for
      degradation; concomitantly, it is required for convergent extension movements in
      gastrulating Xenopus laevis embryos and elongation of animal cap explants, both
      regulated by noncanonical Wnt signaling. In zebrafish, the structurally related
      switch molecule diversin ameliorates renal cysts caused by the depletion of
      inversin, implying that an inhibition of canonical Wnt signaling is required for
      normal renal development. Fluid flow increases inversin levels in ciliated
      tubular epithelial cells and seems to regulate this crucial switch between Wnt
      signaling pathways during renal development.

PMID- 15852008
TI  - Transforming growth factor-beta controls T helper type 1 cell development through
      regulation of natural killer cell interferon-gamma.
AB  - Interferon-gamma and interleukin 12 produced by the innate arm of the immune
      system are important regulators of T helper type 1 (T(H)1) cell development, but
      signals that negatively regulate their expression remain controversial. Here we
      show that transforming growth factor-beta (TGF-beta) controlled T(H)1
      differentiation through the regulation of interferon-gamma produced by natural
      killer (NK) cells. Blockade of TGF-beta signaling in NK cells caused the
      accumulation of a large pool of NK cells secreting copious interferon-gamma,
      responsible for T(H)1 differentiation and protection from leishmania infection.
      In contrast, blockade of TGF-beta signaling in dendritic cells did not affect
      dendritic cell homeostasis or interleukin 12 production, thus indicating a
      previously undescribed demarcation of the function of TGF-beta in NK cells versus
      dendritic cells.

PMID- 15852007
TI  - Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor
      homolog RP105.
AB  - Activation of Toll-like receptor (TLR) signaling by microbial signatures is
      critical to the induction of immune responses. Such responses demand tight
      regulation. RP105 is a TLR homolog thought to be mostly B cell specific, lacking
      a signaling domain. We report here that RP105 expression was wide, directly
      mirroring that of TLR4 on antigen-presenting cells. Moreover, RP105 was a
      specific inhibitor of TLR4 signaling in HEK 293 cells, a function conferred by
      its extracellular domain. Notably, RP105 and its helper molecule, MD-1,
      interacted directly with the TLR4 signaling complex, inhibiting its ability to
      bind microbial ligand. Finally, RP105 regulated TLR4 signaling in dendritic cells
      as well as endotoxin responses in vivo. Thus, our results identify RP105 as a
      physiological negative regulator of TLR4 responses.

PMID- 15852009
TI  - PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through
      the TRP domain.
AB  - The subjective feeling of cold is mediated by the activation of TRPM8 channels in
      thermoreceptive neurons by cold or by cooling agents such as menthol. Here, we
      demonstrate a central role for phosphatidylinositol 4,5-bisphosphate
      (PI(4,5)P(2)) in the activation of recombinant TRPM8 channels by both cold and
      menthol. Moreover, we show that Ca(2+) influx through these channels activates a
      Ca(2+)-sensitive phospholipase C and that the subsequent depletion of PI(4,5)P(2)
      limits channel activity, serving as a unique mechanism for desensitization of
      TRPM8 channels. Finally, we find that mutation of conserved positive residues in
      the highly conserved proximal C-terminal TRP domain of TRPM8 and two other family
      members, TRPM5 and TRPV5, reduces the sensitivity of the channels for PI(4,5)P(2)
      and increases inhibition by PI(4,5)P(2) depletion. These data suggest that the
      TRP domain of these channels may serve as a PI(4,5)P(2)-interacting site and that
      regulation by PI(4,5)P(2) is a common feature of members of the TRP channel
      family.

PMID- 15852006
TI  - Complex haplotypes, copy number polymorphisms and coding variation in two
      recently divergent mouse strains.
AB  - Inbred mouse strains provide the foundation for mouse genetics. By selecting for
      phenotypic features of interest, inbreeding drives genomic evolution and
      eliminates individual variation, while fixing certain sets of alleles that are
      responsible for the trait characteristics of the strain. Mouse strains 129Sv
      (129S5) and C57BL/6J, two of the most widely used inbred lines, diverged from
      common ancestors within the last century, yet very little is known about the
      genomic differences between them. By comparative genomic hybridization and
      sequence analysis of 129S5 short insert libraries, we identified substantial
      structural variation, a complex fine-scale haplotype pattern with a continuous
      distribution of diversity blocks, and extensive nucleotide variation, including
      nonsynonymous coding SNPs and stop codons. Collectively, these genomic changes
      denote the level and direction of allele fixation that has occurred during
      inbreeding and provide a basis for defining what makes these mouse strains
      unique.

PMID- 15852010
TI  - SK channels regulate excitatory synaptic transmission and plasticity in the
      lateral amygdala.
AB  - At glutamatergic synapses, calcium influx through NMDA receptors (NMDARs) is
      required for long-term potentiation (LTP); this is a proposed cellular mechanism
      underlying memory and learning. Here we show that in lateral amygdala pyramidal
      neurons, SK channels are also activated by calcium influx through synaptically
      activated NMDARs, resulting in depression of the synaptic potential. Thus,
      blockade of SK channels by apamin potentiates fast glutamatergic synaptic
      potentials. This potentiation is blocked by the NMDAR antagonist AP5 (D(-)-2
      amino-5-phosphono-valeric acid) or by buffering cytosolic calcium with BAPTA.
      Blockade of SK channels greatly enhances LTP of cortical inputs to lateral
      amygdala pyramidal neurons. These results show that NMDARs and SK channels are
      colocalized at glutamatergic synapses in the lateral amygdala. Calcium influx
      through NMDARs activates SK channels and shunts the resultant excitatory
      postsynaptic potential. These results demonstrate a new role for SK channels as
      postsynaptic regulators of synaptic efficacy.

PMID- 15852011
TI  - SK channels and NMDA receptors form a Ca2+-mediated feedback loop in dendritic
      spines.
AB  - Small-conductance Ca(2+)-activated K(+) channels (SK channels) influence the
      induction of synaptic plasticity at hippocampal CA3-CA1 synapses. We find that in
      mice, SK channels are localized to dendritic spines, and their activity reduces
      the amplitude of evoked synaptic potentials in an NMDA receptor (NMDAR)-dependent
      manner. Using combined two-photon laser scanning microscopy and two-photon laser
      uncaging of glutamate, we show that SK channels regulate NMDAR-dependent Ca(2+)
      influx within individual spines. SK channels are tightly coupled to synaptically
      activated Ca(2+) sources, and their activity reduces the amplitude of NMDAR
      dependent Ca(2+) transients. These effects are mediated by a feedback loop within
      the spine head; during an excitatory postsynaptic potential (EPSP), Ca(2+) influx
      opens SK channels that provide a local shunting current to reduce the EPSP and
      promote rapid Mg(2+) block of the NMDAR. Thus, blocking SK channels facilitates
      the induction of long-term potentiation by enhancing NMDAR-dependent Ca(2+)
      signals within dendritic spines.

PMID- 15852012
TI  - Fast delayed rectifier potassium current is required for circadian neural
      activity.
AB  - In mammals, the precise circadian timing of many biological processes depends on
      the generation of oscillations in neural activity of pacemaker cells in the
      suprachiasmatic nucleus (SCN). The ionic mechanisms that underlie these rhythms
      are largely unknown. Using the mouse brain slice preparation, we show that the
      magnitude of fast delayed rectifier (FDR) potassium currents has a diurnal rhythm
      that peaks during the day. Notably, this rhythm continues in constant darkness,
      providing the first demonstration of the circadian regulation of an intrinsic
      voltage-gated current in mammalian cells. Blocking this current prevented the
      daily rhythm in firing rate in SCN neurons. Kv3.1b and Kv3.2 potassium channels
      were widely distributed within the SCN, with higher expression during the day. We
      conclude that the FDR is necessary for the circadian modulation of electrical
      activity in SCN neurons and represents an important part of the ionic basis for
      the generation of rhythmic output.

PMID- 15852013
TI  - Predicting the orientation of invisible stimuli from activity in human primary
      visual cortex.
AB  - Humans can experience aftereffects from oriented stimuli that are not consciously
      perceived, suggesting that such stimuli receive cortical processing. Determining
      the physiological substrate of such effects has proven elusive owing to the low
      spatial resolution of conventional human neuroimaging techniques compared to the
      size of orientation columns in visual cortex. Here we show that even at
      conventional resolutions it is possible to use fMRI to obtain a direct measure of
      orientation-selective processing in V1. We found that many parts of V1 show
      subtle but reproducible biases to oriented stimuli, and that we could accumulate
      this information across the whole of V1 using multivariate pattern recognition.
      Using this information, we could then successfully predict which one of two
      oriented stimuli a participant was viewing, even when masking rendered that
      stimulus invisible. Our findings show that conventional fMRI can be used to
      reveal feature-selective processing in human cortex, even for invisible stimuli.

PMID- 15852014
TI  - Decoding the visual and subjective contents of the human brain.
AB  - The potential for human neuroimaging to read out the detailed contents of a
      person's mental state has yet to be fully explored. We investigated whether the
      perception of edge orientation, a fundamental visual feature, can be decoded from
      human brain activity measured with functional magnetic resonance imaging (fMRI).
      Using statistical algorithms to classify brain states, we found that ensemble
      fMRI signals in early visual areas could reliably predict on individual trials
      which of eight stimulus orientations the subject was seeing. Moreover, when
      subjects had to attend to one of two overlapping orthogonal gratings, feature
      based attention strongly biased ensemble activity toward the attended
      orientation. These results demonstrate that fMRI activity patterns in early
      visual areas, including primary visual cortex (V1), contain detailed orientation
      information that can reliably predict subjective perception. Our approach
      provides a framework for the readout of fine-tuned representations in the human
      brain and their subjective contents.

PMID- 15852015
TI  - A positive autoregulatory loop of Jak-STAT signaling controls the onset of
      astrogliogenesis.
AB  - During development of the CNS, neurons and glia are generated in a sequential
      manner. The mechanism underlying the later onset of gliogenesis is poorly
      understood, although the cytokine-induced Jak-STAT pathway has been postulated to
      regulate astrogliogenesis. Here, we report that the overall activity of Jak-STAT
      signaling is dynamically regulated in mouse cortical germinal zone during
      development. As such, activated STAT1/3 and STAT-mediated transcription are
      negligible at early, neurogenic stages, when neurogenic factors are highly
      expressed. At later, gliogenic periods, decreased expression of neurogenic
      factors causes robust elevation of STAT activity. Our data demonstrate a positive
      autoregulatory loop whereby STAT1/3 directly induces the expression of various
      components of the Jak-STAT pathway to strengthen STAT signaling and trigger
      astrogliogenesis. Forced activation of Jak-STAT signaling leads to precocious
      astrogliogenesis, and inhibition of this pathway blocks astrocyte
      differentiation. These observations suggest that autoregulation of the Jak-STAT
      pathway controls the onset of astrogliogenesis.

PMID- 15852016
TI  - Development of a humanized monoclonal antibody with therapeutic potential against
      West Nile virus.
AB  - Neutralization of West Nile virus (WNV) in vivo correlates with the development
      of an antibody response against the viral envelope (E) protein. Using random
      mutagenesis and yeast surface display, we defined individual contact residues of
      14 newly generated monoclonal antibodies against domain III of the WNV E protein.
      Monoclonal antibodies that strongly neutralized WNV localized to a surface patch
      on the lateral face of domain III. Convalescent antibodies from individuals who
      had recovered from WNV infection also detected this epitope. One monoclonal
      antibody, E16, neutralized 10 different strains in vitro, and showed therapeutic
      efficacy in mice, even when administered as a single dose 5 d after infection. A
      humanized version of E16 was generated that retained antigen specificity, avidity
      and neutralizing activity. In postexposure therapeutic trials in mice, a single
      dose of humanized E16 protected mice against WNV-induced mortality, and may
      therefore be a viable treatment option against WNV infection in humans.

PMID- 15852017
TI  - A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer
      disease.
AB  - Cholinergic neuron loss is a cardinal feature of Alzheimer disease. Nerve growth
      factor (NGF) stimulates cholinergic function, improves memory and prevents
      cholinergic degeneration in animal models of injury, amyloid overexpression and
      aging. We performed a phase 1 trial of ex vivo NGF gene delivery in eight
      individuals with mild Alzheimer disease, implanting autologous fibroblasts
      genetically modified to express human NGF into the forebrain. After mean follow
      up of 22 months in six subjects, no long-term adverse effects of NGF occurred.
      Evaluation of the Mini-Mental Status Examination and Alzheimer Disease Assessment
      Scale-Cognitive subcomponent suggested improvement in the rate of cognitive
      decline. Serial PET scans showed significant (P < 0.05) increases in cortical 18
      fluorodeoxyglucose after treatment. Brain autopsy from one subject suggested
      robust growth responses to NGF. Additional clinical trials of NGF for Alzheimer
      disease are warranted.

PMID- 15852019
TI  - Electro-tunable optical diode based on photonic bandgap liquid-crystal
      heterojunctions.
AB  - Manipulation of light is in strong demand in information technologies. Among the
      wide range of linear and nonlinear optical devices that have been used, growing
      attention has been paid to photonic crystals that possess a periodic modulation
      of dielectric function. Among many photonic bandgap (PBG) structures, liquid
      crystals with periodic structures are very attractive as self-assembled photonic
      crystals, leading to optical devices such as dye lasers. Here we report a new
      hetero-PBG structure consisting of an anisotropic nematic layer sandwiched
      between two cholesteric liquid-crystal layers with different helical pitches. We
      optically visualized the dispersion relation of this structure, displaying the
      optical diode performance: that is, the non-reciprocal transmission of circular
      polarized light at the photonic-bandgap regions. Transmittance spectra with
      circularly polarized light also reveal the diode performance, which is well
      simulated in calculations that include an electro-tunable diode effect. Lasing
      action was also confirmed to show the diode effect with a particular
      directionality.

PMID- 15852018
TI  - Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease
      in mice.
AB  - Alveolar cell apoptosis is involved in the pathogenesis of emphysema, a prevalent
      disease primarily caused by cigarette smoking. We report that ceramide, a second
      messenger lipid, is a crucial mediator of alveolar destruction in emphysema.
      Inhibition of enzymes controlling de novo ceramide synthesis prevented alveolar
      cell apoptosis, oxidative stress and emphysema caused by blockade of the vascular
      endothelial growth factor (VEGF) receptors in both rats and mice. Emphysema was
      reproduced with intratracheal instillation of ceramide in naive mice. Excessive
      ceramide triggers a feed-forward mechanism mediated by activation of secretory
      acid sphingomyelinase, as suggested by experiments with neutralizing ceramide
      antibody in mice and with acid sphingomyelinase-deficient fibroblasts.
      Concomitant augmentation of signaling initiated by a prosurvival metabolite,
      sphingosine-1-phosphate, prevented lung apoptosis, implying that a balance
      between ceramide and sphingosine-1-phosphate is required for maintenance of
      alveolar septal integrity. Finally, increased lung ceramides in individuals with
      smoking-induced emphysema suggests that ceramide upregulation may be a crucial
      pathogenic element and a promising target in this disease that currently lacks
      effective therapies.

PMID- 15852020
TI  - How superheated crystals melt.
AB  - In experiments where intense radiation penetrates into the bulk of a solid and
      causes ultrafast (femtosecond) heating, the superheated crystalline solid melts
      from within at a temperature above the equilibrium melting temperature. But what
      happens on the atomic scale as a solid loses crystalline order remains an open
      question. Molecular dynamics modelling allows the position of every atom to be
      traced at each instant, as a crystal transforms from solid to liquid. Here we use
      such detailed atomistic simulations, relevant for aluminium, to show that the
      thermal fluctuation initiating melting is an aggregate typically with 6-7
      interstitials and 3-4 vacancies. This mechanism differs from those that have
      traditionally been proposed, which generally involve many more atoms at the
      initial melting stage.

PMID- 15852021
TI  - Target accessibility dictates the potency of human RISC.
AB  - In this report, we examined the effect of increased target site access on
      activated human RNA-induced silencing complex (RISC(*)) catalysis. Kinetic
      studies revealed that siRNA-programmed RISC(*) cleaved target RNA with higher
      efficiencies when target site access was increased. These results provide
      evidence that target site access is linked to RISC(*) catalysis.

PMID- 15852022
TI  - Structural basis of TEA blockade in a model potassium channel.
AB  - Potassium channels catalyze the selective transfer of potassium across the cell
      membrane and are essential for setting the resting potential in cells,
      controlling heart rate and modulating the firing pattern in neurons.
      Tetraethylammonium (TEA) blocks ion conduction through potassium channels in a
      voltage-dependent manner from both sides of the membrane. Here we show the
      structural basis of TEA blockade by cocrystallizing the prokaryotic potassium
      channel KcsA with two selective TEA analogs. TEA binding at both sites alters ion
      occupancy in the selectivity filter; these findings underlie the mutual
      destabilization and voltage-dependence of TEA blockade. We propose that TEA
      blocks potassium channels by acting as a potassium analog at the dehydration
      transition step during permeation.

PMID- 15852023
TI  - The Rad50 hook domain is a critical determinant of Mre11 complex functions.
AB  - The Mre11 complex (in Saccharomyces cerevisiae: Mre11, Rad50 and Xrs2) influences
      multiple facets of chromosome break metabolism. A conserved feature of the Mre11
      complex is a zinc-coordinating motif in Rad50 called the Rad50 hook. We
      established a diploid yeast strain, rad50(hook), in which Rad50 is encoded in
      halves, one from each of the two RAD50 alleles, with the residues constituting
      the hook deleted. In all respects, rad50(hook) phenocopies complete Rad50
      deficiency. Replacing the hook domain with a ligand-inducible FKBP dimerization
      cassette partially mitigated all phenotypes in a ligand-dependent manner. The
      data indicate that the Rad50 hook is critical for Mre11 complex-dependent DNA
      repair, telomere maintenance and meiotic double-strand break formation. Sister
      chromatid cohesion was unaffected by Rad50 deficiency, suggesting that molecular
      bridging required for recombinational DNA repair is qualitatively distinct from
      cohesin-mediated sister chromatid cohesion.

PMID- 15852024
TI  - Lower incidence of Bronchiolitis obliterans in allogeneic hematopoietic stem cell
      transplantation with reduced-intensity conditioning compared with myeloablative
      conditioning.
AB  - Bronchiolitis obliterans (BO) is one of the most devastating complications after
      allogeneic stem cell transplantation (HSCT). However, its true pathogenesis is
      still to be elucidated. We conducted this study to find whether tissue damage due
      to high-dose chemo-radiotherapy is related to its pathogenesis. In all, 144
      patients who received allogeneic HSCT between May 1999 and October 2001, and
      survived more than 80 days after transplant, were analyzed. Clinical course,
      pulmonary function tests, imaging studies including CT scan, and pathology
      results were reviewed. The overall incidence of BO was 9.7% (14/144). The
      cumulative incidence of BO at 2 years after transplant was 17% with myeloablative
      conditioning, and 2.3% with reduced intensity conditioning (P=0.024).
      Multivariate analysis showed that myeloablative conditioning was the only factor
      which affected the incidence of BO. Development of BO did not significantly
      affect the overall survival of patients. However, if they developed BO earlier
      than 200 days post transplant, the prognosis was significantly worse than if they
      developed it later than 200 days post transplant (P=0.003) or if they did not
      develop BO (P=0.002). Our results imply that tissue damage secondary to intensive
      chemo-radiotherapy may contribute to the pathogenesis of BO.

PMID- 15852025
TI  - Prospective study of extracorporeal photopheresis in steroid-refractory or
      steroid-resistant extensive chronic graft-versus-host disease: analysis of
      response and survival incorporating prognostic factors.
AB  - We enrolled 25 patients with extensive, steroid-refractory chronic graft-versus
      host disease (cGVHD) in a prospective trial evaluating the efficacy of
      extracorporeal photophoresis (ECP) in both skin and visceral cGVHD. The median
      time from transplant to initiation of ECP was 790 days. ECP was administered for
      2 consecutive days every 2 weeks in 17 patients and once a week in eight patients
      until best response or stable disease. The median duration of therapy was 9
      months (range 3-24 months). In all, 20 patients had improvement in cutaneous GVHD
      and six had healing of oral ulcerations. Steroid sparing or discontinuation of
      immunosuppressive medications was possible in 80% of patients. Response rates
      were similar between patients receiving treatment weekly vs every 2 weeks and in
      patients commencing ECP less than vs greater than 18 months from transplant (70
      vs 66%). When patients were stratified based on the Akpek prognostic score, there
      was no difference in overall response between the favorable (Akpek score<2.5) and
      unfavorable risk groups, but patients with progressive onset cGVHD tended to have
      a higher response than those with de novo onset. In summary, we report
      improvement in skin and/or visceral cGVHD in 71% overall and 61% of high-risk
      patients.

PMID- 15852026
TI  - Unexpected immune complications in patients with non-Hodgkin's lymphoma receiving
      CD34-selected autologous peripheral stem cell transplantation.

PMID- 15852027
TI  - Candida krusei fungemia in an unrelated allogeneic hematopoietic stem cell
      transplant patient successfully treated with Caspofungin.

PMID- 15852028
TI  - Cytokine expression during acute graft-versus-host disease after allogeneic
      peripheral stem cell transplantation.
AB  - Acute graft-versus-host disease (aGVHD) is one of the major problems following
      allogeneic peripheral blood stem cell transplantation (allo-PBSCT). In order to
      investigate the pathogenesis of human aGVHD, we analyzed cytokine gene expression
      and cytokine secretion by peripheral blood mononuclear cells (PBMC) in 30
      patients who underwent allo-PBSCT. In this study, reverse transcription
      polymerase chain reaction (RT-PCR) was used to explore the mRNA expression of
      interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-10 and IL-12 in the PBMC of
      allo-PBSCT patients with aGVHD and in controls. The concentrations of these
      cytokines and of IL-18 were also measured by means of ELISA in medium obtained
      from cultured leukocytes after stimulation with PHA or LPS. Compared with the
      normal allo-PBSCT group (n=14), IL-2 and IFN-gamma were detected more frequently
      in aGVHD group (n=16). IL-12 and IL-18 were elevated, while IL-10 level decreased
      in the same group. There is no difference in IL-4 gene expression between
      patients with or without aGVHD, but the concentration of IL-4 for patients with
      grade II-IV aGVHD decreased. These data suggest that IL-2, IFN-gamma, IL-12 and
      IL-18 play important roles in the development of aGVHD in humans.

PMID- 15852029
TI  - Inhibition of the antigen-induced activation of rodent mast cells by putative
      Janus kinase 3 inhibitors WHI-P131 and WHI-P154 in a Janus kinase 3-independent
      manner.
AB  - We analyzed the effects of the Janus kinase 3 (Jak3)-specific inhibitor WHI-P131
      (4-(4'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline) and the Jak3/Syk inhibitor
      WHI-P154 (4-(3'-bromo-4'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline) on the
      antigen-induced activation of mast cells. In the rat mast cell line RBL-2H3, both
      WHI-P131 and WHI-P154 inhibited the antigen-induced degranulation and
      phosphorylation of p44/42 mitogen-activated protein kinase (MAPK), p38 MAPK and c
      Jun N-terminal kinase (JNK). The phosphorylation of Gab2, Akt and Vav was also
      inhibited by WHI-P131 and WHI-P154, indicating that these inhibitors suppress the
      activation of phosphatidylinositol 3-kinase (PI3K). In bone marrow-derived mast
      cells (BMMCs) from Jak3-deficient (Jak3-/-) mice, degranulation and activation of
      MAPKs were induced by the antigen in almost the same extent as in BMMCs from wild
      type mice. In addition, the antigen-induced degranulation and activation of MAPKs
      were inhibited by WHI-P131 and WHI-P154 in both groups of BMMCs, indicating that
      these compounds inhibit a certain step except for Jak3. The antigen-induced
      increase in the activity of Fyn, a probable tyrosine kinase of Gab2, was also
      inhibited by WHI-P131 and WHI-P154 in RBL-2H3 cells. In BMMCs from Jak3-/- mice,
      the antigen stimulation induced tyrosine phosphorylation of Fyn, which was
      inhibited by WHI-P131, as well as in BMMCs from wild-type mice and in RBL-2H3
      cells. These findings suggest that Jak3 does not play a significant role in the
      antigen-induced degranulation and phosphorylation of MAPKs, and that WHI-P131 and
      WHI-P154 inhibit the PI3K pathway by preventing the antigen-induced activation of
      Fyn, thus inhibiting the antigen-induced degranulation and phosphorylation of
      MAPKs in mast cells.

PMID- 15852030
TI  - The antidepressant imipramine inhibits M current by activating a
      phosphatidylinositol 4,5-bisphosphate (PIP2)-dependent pathway in rat sympathetic
      neurones.
AB  - Little is known about the intracellular actions of imipramine (IMI) in the
      regulation of ion channels. We tested the action of IMI on the intracellular
      cascade that regulates M current (I(M)) in superior cervical ganglion neurones
      (SCGs). Dialysis of the cells with GDPbetaS, a G protein signaling blocker, did
      not disrupt the inhibition of I(M). When we incubated the cells with the
      phospholipase C (PLC) inhibitor U73122, it prevented the I(M) inhibition by IMI.
      Also, when we dialyzed the cells with an intracellular Ca2+ chelator, it did not
      disrupt I(M) inhibition by IMI, as occurs in the M1 cascade. When we incubated
      the cells with the generic kinase inhibitor wortmannin, it prevented the recovery
      of I(M) from the inhibition by IMI. Also, when we applied phosphatidylinositol
      4,5-bisphosphate (PIP2) intracellularly, it diminished the inhibition of I(M) by
      IMI. Our findings suggest that PLC is the target for IMI, that recovery of I(M)
      needs lipid phosphorylation for PIP2 resynthesis, and that IMI inhibits I(M) by
      activating a PLC-dependent pathway, likely by decreasing the concentration of
      PIP2.

PMID- 15852031
TI  - Epidermal growth factor receptor tyrosine kinase-mediated signalling contributes
      to diabetes-induced vascular dysfunction in the mesenteric bed.
AB  - In order to characterize the roles of tyrosine kinases (TKs) and epidermal growth
      factor receptor (EGFR) in diabetes-induced vascular dysfunction, we investigated
      the ability of a chronic administration of genistein, a broad-spectrum inhibitor
      of TKs and AG1478, a specific inhibitor of EGFR TK activity to modulate the
      altered vasoreactivity of the perfused mesenteric bed to common vasoconstrictors
      and vasodilators in streptozotocin (STZ)-induced diabetes in rats. The
      vasoconstrictor responses induced by norepinephrine (NE), endothelin-1 (ET-1) and
      angiotensin II (Ang II), were significantly increased, whereas vasodilator
      responses to carbachol and histamine were significantly reduced in the perfused
      mesenteric bed of STZ-induced diabetic rats in comparison with healthy rats.
      Treatment of diabetic animals with genistein or AG1478 produced a significant
      normalization of the altered agonist-induced vasoconstrictor and vasodilator
      responses without affecting blood glucose levels. In contrast, neither inhibitor
      had any effect on the vascular responsiveness of control (nondiabetic) animals.
      Treatment of diabetic animals with diadzein, an inactive analogue of genistein,
      did not affect the vasoconstrictor and vasodilator responses in control or
      diabetic animals. Phosphorylated EGFR levels were markedly raised in the
      mesenteric bed from diabetic animals and were normalized upon treatment with
      AG1478 or genistein. These data suggest that activation of TK-mediated pathways,
      including EGFR TK signalling are involved in the development of diabetic vascular
      dysfunction.

PMID- 15852032
TI  - Direct gas measurements indicate that the novel cyclooxygenase inhibitor AZD3582
      is an effective nitric oxide donor in vivo.
AB  - 1. AZD3582 [4-(nitrooxy)butyl-(2S)-2-(6-methoxy-2-naphthyl)propanoate] is a COX
      inhibiting nitric oxide donor that inhibits COX-1 and COX-2. It is as effective
      as naproxen in models of pain and inflammation, but causes less gastroduodenal
      damage. Nitric oxide (NO) is generated from AZD3582 in vitro, and this study
      sought to show that the drug donates NO in vivo. 2. In anaesthetised male New
      Zealand white rabbits, the endogenous NO concentration in exhaled air was reduced
      by N(G)-nitro-L-arginine methyl ester (L-NAME) (30 mg kg(- 1) i.v.) from 33.5+/
      1.0 ppb (mean+/-s.e.m.; n=6 per group) to 3.0+/-1.0 ppb, while increasing blood
      pressure and reducing heart rate. AZD3582 (0.2, 0.6, 2.0 or 6.0 micromol kg(- 1)
      min(- 1)) given 30 min after L-NAME increased the concentration of NO in exhaled
      air (P<0.05), decreased blood pressure and increased heart rate in a dose
      dependent manner versus L-NAME control values. The peak mean NO concentration
      obtained was 44+/-8.0 ppb. 3. In in situ-perfused rabbit lungs, L-NAME (185
      micromol l(- 1)) reduced the NO concentration in exhaled air from 106+/-13 to
      4.0+/-0.4 ppb (n=5). Addition of AZD3582 (6 micromol min(- 1)) to the perfusate
      produced an initial rapid increase in the NO concentration in exhaled air,
      followed by a sustained, but lower plateau. Infusion of L-NAME increased, and
      AZD3582 decreased, pulmonary arterial pressure. 4. In both anaesthetised rabbits
      and in the perfused lungs, brief periods of hypoxia increased NO concentrations
      generated by AZD3582. 5. We conclude that, in rabbits, AZD3582 donates NO in vivo
      with characteristics similar to those reported for nitroglycerin and isosorbide
      nitrates

PMID- 15852033
TI  - Prednisolone augments superoxide formation in porcine pulmonary artery
      endothelial cells through differential effects on the expression of nitric oxide
      synthase and NADPH oxidase.
AB  - 1. Prednisolone, a potent anti-inflammatory drug, has proved ineffective in
      treating acute respiratory distress syndrome (ARDS). ARDS is associated with
      superoxide (O(2)(*-)) generation, which negates nitric oxide (NO). NO also
      downregulates NADPH oxidase and inhibits O(2)(*-) formation. A possible reason
      for the lack of effect of prednisolone may due to an inhibition of eNOS
      expression. In order to test this proposal, the effect of prednisolone on O(2)(*
      ) formation and the expression of gp91(phox) (catalytic subunit of NADPH oxidase)
      and eNOS in pig pulmonary artery (PA) segments and PA endothelial cells (PAECs)
      and PA vascular smooth muscle cells (PAVSMCs) was investigated. 2. PA segments
      and cells were incubated with prednisolone and tumour necrosis factor-alpha (TNF
      alpha) for 16 h. O(2)(*-) formation was measured spectrophometrically and
      gp91(phox) and eNOS expression by Western blotting. The role of the NO-cGMP axis
      was studied using morpholinosydnonimine hydrochloride, the diethylamine/NO
      complex (DETA-NONOate), the guanylyl cyclase inhibitor, 1H-{1,2,4}oxadiazolo{4,3
      a}quinoxalin-1-one (ODQ) and the stable cGMP analogues, 8-bromo cGMP and 8-(4
      chlorophenylthio)-cGMP (8-pCPT-cGMP). NO release was studied using a fluorescence
      assay and O(2)(*-)-NO interactions with a nitrite/nitrate assay. 3. Prednisolone
      elicited significant increase in O(2)(*-) formation in intact PA segments and
      PAECs, but not PAVSMCs, in a concentration-dependent manner. In endothelium
      denuded segments, prednisolone slightly enhanced O(2)(*-) release. TNF-alpha
      further increased prednisolone-enhanced O(2)(*-) formation in intact PA segments
      and PAECs. NADPH oxidase inhibitor, apocynin, inhibited O(2)(*-) formation.
      Increased O(2)(*-) release and gp91(phox) expression in PAECs elicited by
      prednisolone was blocked by SIN-1 (3-morpholinosydnonimine hydrochloride), DETA
      NONOate, 8-pCPT-cGMP and 8-bromo cGMP. The effects of SIN-1 on gp91(phox)
      expression were reversed by ODQ. Finally, eNOS protein expression was
      significantly reduced by prednisolone. 4. Prednisolone increases O(2)(*-) in
      porcine PAECs through a downregulation of endogenous eNOS expression. Since the
      NO-cGMP axis inhibits gp91(phox) expression, the resultant decrease in endogenous
      NO formation then augments NADPH oxidase activity, which in turn results in
      increased O(2)(*-) formation. Since O(2)(*-) promotes inflammation, this
      mechanism may explain why prednisolone is ineffective in treating ARDS.
      Therapeutically, the coadministration of an NO donor may render prednisolone more
      effective in treating ARDS.

PMID- 15852035
TI  - Identification of WIN55212-3 as a competitive neutral antagonist of the human
      cannabinoid CB2 receptor.
AB  - 1. Several G protein-coupled receptors (GPCRs), including cannabinoid CB(1) and
      CB(2) receptors, show constitutive activity under heterologous expression. Such a
      tonic response is generated in the absence of an activating ligand, and can be
      inhibited by inverse agonists. Neutral antagonists, however, are silent at such
      receptors, but can reverse both agonist and inverse agonist responses. To date,
      no neutral antagonist for the CB(2) receptor has been reported. 2. Here, by
      monitoring receptor-dependent G protein activation, we demonstrate that WIN55212
      3 acts as a neutral antagonist at the human CB(2) (hCB(2)) receptor. WIN55212-3
      alone, at concentrations </=10(-4) M, behaved as a silent ligand exhibiting no
      agonist or inverse agonist activity. However, WIN55212-3 competitively
      antagonized cannabinoid agonist CP-55,940-stimulated responses (pA(2) 6.1).
      Importantly, the inverse agonism evoked by SR144528 in hCB(2) was dose
      dependently reversed by WIN55212-3 (pEC(50) 5.3+/-0.2), indicating true neutral
      antagonist behavior. 3. Furthermore, WIN55212-3 also antagonized CB(1) receptor
      signaling in a competitive manner (pA(2) 5.6), but behaved as a partial inverse
      agonist (pIC(50) 5.5+/-0.1) at the constitutively active human CB(1). 4.
      Additionally, WIN55212-3 antagonized signaling of the human melatonin MT(1)
      receptor, with modest activity at the human muscarinic M4 receptor, but it was
      inactive towards several other GPCRs. 5. These data identify WIN55212-3 as a true
      neutral hCB(2) receptor antagonist. WIN55212-3 offers a valuable tool for further
      characterization of ligand activities at the CB(2) receptor and may serve as a
      lead compound in further efforts to develop more potent and selective neutral
      CB(2) receptor antagonists.

PMID- 15852034
TI  - Phase 2 ventricular arrhythmias in acute myocardial infarction: a neglected
      target for therapeutic antiarrhythmic drug development and for safety
      pharmacology evaluation.
AB  - Ventricular fibrillation (VF), a cause of sudden cardiac death (SCD) in the
      setting of acute myocardial infarction (MI), remains a major therapeutic
      challenge. In humans, VF may occur within minutes or hours after the onset of
      chest pain, so its precise timing in relation to the onset of ischaemia is
      variable. Moreover, because VF usually occurs unobserved, out of hospital, and is
      usually lethal in the absence of intervention, its precise timing of onset is
      actually unknown in most patients. In animal models, the timing of susceptibility
      to VF is much better characterised. It occurs in two distinct phases. Early VF
      (defined as phase 1 VF, with possible subphases 1a and 1b in some animal species)
      occurs during the first 30 min of ischaemia when most myocardial injury is still
      reversible. Late VF, defined as phase 2 VF, occurs when myocardial necrosis is
      becoming established (after more than 90 min of ischaemia). Although much is
      known about the mechanisms and pharmacology of phase 1 VF, little is known about
      phase 2 VF. By reviewing a range of different types of data we have outlined the
      likely mechanisms and clinical relevance of phase 2 VF, and have evaluated
      possible future directions to help evolve a strategy for its suppression by
      drugs. The possibility that a proarrhythmic effect on phase 2 VF contributes to
      the adverse cardiac effects of certain cardiac and noncardiac drugs is also
      discussed in relation to the emerging field of safety pharmacology. It is
      concluded that suppression of phase 2 as well as phase 1 VF will almost certainly
      be necessary if drugs of the future are to achieve what drugs of the past and
      present have failed to achieve: full protection against SCD. Likewise, safety
      will require avoidance of exacerbation of phase 2 as well as phase 1 VF.

PMID- 15852036
TI  - Nonpeptidic urotensin-II receptor antagonists I: in vitro pharmacological
      characterization of SB-706375.
AB  - 1. SB-706375 potently inhibited [(125)I]hU-II binding to both mammalian
      recombinant and 'native' UT receptors (K(i) 4.7+/-1.5 to 20.7+/-3.6 nM at rodent,
      feline and primate recombinant UT receptors and K(i) 5.4+/-0.4 nM at the
      endogenous UT receptor in SJRH30 cells). 2. Prior exposure to SB-706375 (1
      microM, 30 min) did not alter [(125)I]hU-II binding affinity or density in
      recombinant cells (K(D) 3.1+/-0.4 vs 5.8+/-0.9 nM and B(max) 3.1+/-1.0 vs 2.8+/
      0.8 pmol mg(-1)) consistent with a reversible mode of action. 3. The novel,
      nonpeptidic radioligand [(3)H]SB-657510, a close analogue of SB-706375, bound to
      the monkey UT receptor (K(D) 2.6+/-0.4 nM, B(max) 0.86+/-0.12 pmol mg(-1)) in a
      manner that was inhibited by both U-II isopeptides and SB-706375 (K(i) 4.6+/-1.4
      to 17.6+/-5.4 nM) consistent with the sulphonamides and native U-II ligands
      sharing a common UT receptor binding domain. 4. SB-706375 was a potent,
      competitive hU-II antagonist across species with pK(b) 7.29-8.00 in HEK293-UT
      receptor cells (inhibition of [Ca(2+)](i)-mobilization) and pK(b) 7.47 in rat
      isolated aorta (inhibition of contraction). SB-706375 also reversed tone
      established in the rat aorta by prior exposure to hU-II (K(app) approximately 20
      nM). 5. SB-706375 was a selective U-II antagonist with >/=100-fold selectivity
      for the human UT receptor compared to 86 distinct receptors, ion channels,
      enzymes, transporters and nuclear hormones (K(i)/IC(50)>1 microM). Accordingly,
      the contractile responses induced in isolated aortae by KCl, phenylephrine,
      angiotensin II and endothelin-1 were unaltered by SB-706375 (1 microM). 6. In
      summary, SB-706375 is a high-affinity, surmountable, reversible and selective
      nonpeptide UT receptor antagonist with cross-species activity that will assist in
      delineating the pathophysiological actions of U-II in mammals.

PMID- 15852037
TI  - The involvement of nitric oxide in the enhanced expression of mu-opioid receptors
      during intestinal inflammation in mice.
AB  - Intestinal inflammation enhances the potency of mu-opioid receptor (MOR) agonists
      inhibiting gastrointestinal transit and increases the expression of MOR in mice
      intestine. The precise mechanisms implicated in the increased expression of MOR
      during intestinal inflammation are not known. The aim of the study is to evaluate
      if nitric oxide released during intestinal inflammation could modulate MOR gene
      expression and affect gastrointestinal transit. Intestinal inflammation was
      induced by the intragastric administration of croton oil. In CD-1 mice, with and
      without inflammation, we evaluated the anti-transit effects of morphine in
      animals treated with NOS inhibitors (L-NAME and L-NIL) and the intestinal levels
      of iNOS enzyme mRNA. The anti-transit effects of morphine and the expression of
      MOR mRNA in the gut of wild-type (WT) and iNOS-/- mice were also assessed.
      Gastrointestinal transit was measured with charcoal meal and mRNA levels
      determined by real-time PCR. In CD-1 mice, inflammation induced a 10-fold
      increase (P<0.0001) in iNOS mRNA levels in the gut. The absence of iNOS gene and
      treatment of CD-1 mice with L-NAME or L-NIL abolished the increased antitransit
      effects of morphine observed during inflammation. Moreover, although the basal
      levels of MOR mRNA were similar in WT and iNOS animals (-/-), intestinal
      inflammation only increased the MOR expression in the gut of WT (P<0.01) but not
      in iNOS-/- mice. The results suggest that nitric oxide derived from the increased
      expression of iNOS is implicated in the enhanced effects of morphine and in the
      upregulation of MOR gene transcription observed during intestinal inflammation.

PMID- 15852038
TI  - Mechanisms underlying the relaxation response induced by bradykinin in the
      epithelium-intact guinea-pig trachea in vitro.
AB  - In this study, we investigated some of the signalling pathways involved in
      bradykinin (BK)-induced relaxation in epithelium-intact strips of the guinea-pig
      trachea (GPT + E). BK induced time- and concentration-dependent relaxation of GPT
      + E. Similar responses were observed for prostaglandin E2 (PGE2) or the
      combination of subthreshold concentrations of BK plus PGE2. The nonselective
      cyclooxygenase (COX) inhibitors indomethacin or pyroxicam, or the selective COX-2
      inhibitors DFU, NS 398 or rofecoxib, but not the selective COX-1 inhibitor SC
      560, all abolished BK-induced relaxation. The tyrosine kinase inhibitors
      herbimycin A and AG 490 also abolished BK-induced relaxation in GPT + E. The
      nonselective nitric oxide synthase (NOS) inhibitor 7-NINA concentration
      dependently inhibited BK effects. BK-induced relaxation was prevented by the
      selective antagonists for EP3 (L 826266), but not by EP1 (SC 19221), EP1/EP2 (AH
      6809) or EP4 (L161982) receptor antagonists. Otherwise, the selective inhibitors
      of protein kinases A, G and C, mitogen-activated protein kinases, phospholipases
      C and A2, nuclear factor-kappaB or potassium channels all failed to significantly
      interfere with BK-mediated relaxation.BK caused a marked increase in PGE2 levels,
      an effect that was prevented by NS 398, HOE 140 or AG 490. COX-2 expression did
      not differ in preparations with or without epithelium, and it was not changed by
      BK stimulation. However, incubation with BK significantly increased the
      endothelial NOS (eNOS) and neuronal NOS (nNOS) expression, independent of the
      epithelium integrity. Our results indicate that BK-induced relaxation in GPT + E
      depends on prostanoids (probably PGE2 acting via EP3 receptors) and NO release
      and seems to involve complex interactions between kinin B2 receptors, COX-2,
      nNOS, eNOS and tyrosine kinases.

PMID- 15852039
TI  - Diabetes-induced changes in the 5-hydroxytryptamine inhibitory receptors involved
      in the pressor effect elicited by sympathetic stimulation in the pithed rat.
AB  - 1. We investigated the effect of alloxan-induced diabetes on the inhibitory
      mechanisms of 5-hydroxytryptamine (5-HT) in the pressor responses induced by
      stimulation of sympathetic vasopressor outflow in pithed rats, and analysed the
      type and/or subtype of 5-HT receptors involved. 2. Diabetes was induced in male
      Wistar rats by a single s.c. injection of alloxan, then 4 weeks later, they were
      anaesthetized, pretreated with atropine and pithed. Electrical stimulation of the
      sympathetic outflow from the spinal cord (0.1, 0.5, 1 and 5 Hz) resulted in
      frequency-dependent increases in blood pressure. 3. Intravenous infusions of 5-HT
      (1-80 microg kg(-1) min(-1)) reduced the pressor effects obtained by electrical
      stimulation. The 5-HT(1) receptor agonist 5-carboxamidotryptamine, 5-CT (5 microg
      kg(-1) min(-1)), caused an inhibition of the pressor response, whereas the
      selective 5-HT(2) receptor agonist, alpha-methyl-5-HT (5 microg kg(-1) min(-1))
      and the selective 5-HT(3) receptor agonist, 1-phenylbiguanide (40 microg kg(-1)
      min(-1)), did not modify the sympathetic pressor responses. 5-HT had no effect on
      exogenous noradrenaline (NA)-induced pressor responses. 4. The inhibition of
      electrically induced pressor responses by 5-HT (10 microg kg(-1) min(-1)) was
      unable to be elicited after i.v. treatment with methiothepin (100 microg kg(-1))
      because of the marked inhibition produced by methiothepin alone. The 5-HT-induced
      inhibition was blocked after i.v. administration of WAY-100,635 (100 microg kg(
      1)) and not affected by ritanserin (1 mg kg(-1)), MDL 72222 (2 mg kg(-1)). 5. The
      selective 5-HT(1A) receptor agonist, 8-hydroxydipropylaminotretalin hydrobromide
      (8-OH-DPAT) (5-20 microg kg(-1) min(-1)) but neither the rodent 5-HT(1B) receptor
      agonist, CGS-12066B (5 microg kg(-1) min(-1)), nor the selective nonrodent 5
      HT(1B) and 5-HT(1D) receptor agonist, L-694,247 (5 and 40 microg kg(-1) min(-1)),
      inhibited the electrically induced pressor response. The selective 5-HT(1A)
      receptor antagonist, WAY-100,635 (100 microg kg(-1)), blocked the inhibition
      induced by 8-OH-DPAT (10 microg kg(-1) min(-1)). 8-OH-DPAT had no effect on
      exogenous NA-induced pressor responses. 6. Experimental diabetes produces changes
      in the inhibitory effect induced by 5-HT on electrically induced sympathetic
      pressor responses, such that the inhibitory action induced by 5-HT in diabetic
      pithed rats is mediated by prejunctional 5-HT(1A) receptors.

PMID- 15852040
TI  - Construction of a natural panel of 11p11.2 deletions and further delineation of
      the critical region involved in Potocki-Shaffer syndrome.
AB  - Potocki-Shaffer syndrome (PSS) is a contiguous gene deletion syndrome that
      results from haploinsufficiency of at least two genes within the short arm of
      chromosome 11[del(11)(p11.2p12)]. The clinical features of PSS can include
      developmental delay, mental retardation, multiple exostoses, parietal foramina,
      enlarged anterior fontanel, minor craniofacial anomalies, ophthalmologic
      anomalies, and genital abnormalities in males. We constructed a natural panel of
      11p11.2-p13 deletions using cell lines from 10 affected individuals, fluorescence
      in situ hybridization (FISH), microsatellite analyses, and array-based
      comparative genomic hybridization (array CGH). We then compared the deletion
      sizes and clinical features between affected individuals. The full spectrum of
      PSS manifests when deletions are at least 2.1 Mb in size, spanning from D11S1393
      to D11S1385/D11S1319 (44.6-46.7 Mb from the 11p terminus) and encompassing EXT2,
      responsible for multiple exostoses, and ALX4, causing parietal foramina. Yet one
      subject with parietal foramina whose deletion does not include ALX4 indicates
      that ALX4 in this subject may be rendered functionally haploinsufficient by a
      position effect. Based on comparative deletion mapping of eight individuals with
      the full PSS syndrome including mental retardation and two PSS families with no
      mental retardation, at least one gene related to mental retardation is likely
      located between D11S554 and D11S1385/D11S1319, 45.6-46.7 Mb from the 11p
      terminus.

PMID- 15852042
TI  - MicroRNA biogenesis: coordinated cropping and dicing.
AB  - The recent discovery of microRNAs (miRNAs) took many by surprise because of their
      unorthodox features and widespread functions. These tiny, approximately 22
      nucleotide, RNAs control several pathways including developmental timing,
      haematopoiesis, organogenesis, apoptosis, cell proliferation and possibly even
      tumorigenesis. Among the most pressing questions regarding this unusual class of
      regulatory miRNA-encoding genes is how miRNAs are produced in cells and how the
      genes themselves are controlled by various regulatory networks.

PMID- 15852043
TI  - Moving messages: the intracellular localization of mRNAs.
AB  - mRNA localization is a common mechanism for targeting proteins to regions of the
      cell where they are required. It has an essential role in localizing cytoplasmic
      determinants, controlling the direction of protein secretion and allowing the
      local control of protein synthesis in neurons. New methods for in vivo labelling
      have revealed that several mRNAs are transported by motor proteins, but how most
      mRNAs are coupled to these proteins remains obscure.

PMID- 15852044
TI  - Prevention of diet-induced obesity by dietary isomerized hop extract containing
      isohumulones, in rodents.
AB  - OBJECTIVE: Isomerized hop extract (IHE), which consists mainly of isohumulones
      and is required in the beer brewing process, was investigated for its effects on
      diet-induced obesity in two strains of mice. DESIGN: C57BL/6N and KK-A(y) mice
      were fed a standard or high-fat diet containing IHE and their body and tissue
      weights were measured at various time points. Oral glucose tolerance tests (OGTT)
      and insulin tolerance tests (ITT) were carried out in high-fat diet-fed C57BL/6N
      mice. The effects of IHE on intestinal lipid absorption were examined in Wistar
      rats using a plasma triacylglycerol assay after oral administration of a lipid
      emulsion. Fecal lipid levels were also measured in these animals after they were
      fed a high-fat diet containing IHE for 15 days. The effects of IHE on pancreatic
      lipase activity and the expression of genes involved in hepatic lipid metabolism
      were also examined using an in vitro assay and quantitative RT-PCR, respectively.
      RESULTS: Supplementation of high-fat-containing chow with IHE reduced body weight
      gain and improved glucose tolerance in our experimental mice. A reduction in body
      weight gain was also observed in C57BL/6N mice fed a standard diet containing
      IHE. Wistar rats fed a high-fat diet containing IHE showed reduced plasma
      triacylglycerol levels and an increase in their fecal lipid excretion. Similarly,
      their pancreatic lipase activity was inhibited and their elevation in plasma
      triacylglycerol levels seen after the oral administration of lipid emulsion was
      significantly suppressed. IHE-fed mice showed an increased expression in their
      lipid oxidation genes and a decreased expression in genes involved in
      triacylglycerol biosynthesis. CONCLUSION: The inhibition of intestinal dietary
      fat absorption may be the mechanism by which IHE induces its weight-lowering
      effects in high-fat diet-fed mice. The modulatory effect of IHE on lipid
      metabolism may also, at least partly, be responsible for its beneficial effects
      on body weight gain. These results suggest that IHE may be helpful in humans in
      preventing diet-induced obesity and perhaps even metabolic syndrome, the latter
      of which is known to be associated with obesity.

PMID- 15852045
TI  - Trends in overweight and obesity from 1985 to 2002 in Goteborg, West Sweden.
AB  - OBJECTIVE: To study secular trends in overweight and selected correlates in men
      and women in Goteborg, Sweden. DESIGN: Cross-sequential population-based surveys.
      SUBJECTS: A total of 2931 female and 2691 male subjects aged 25-64 y participated
      in WHO MONICA surveys (1985, 1990, 1995) and the INTERGENE study (2002).
      MEASUREMENTS: Body mass index (BMI), waist-to-hip ratio (WHR), prevalence of
      overweight (BMI> or =25 kg/m(2)), and obesity (BMI> or =30 kg/m(2)). RESULTS:
      Mean body weight increased by 3.3 kg for women and 5 kg for men, with a
      significant upward trend for BMI in men but not women over the 17-y observation
      period. The prevalence of overweight and obesity increased significantly in both
      sexes over the period. The largest increase was observed in men, and in women
      aged 25-34 y. In 2002, the prevalence of overweight was 38% in women and 58% in
      men, and the prevalence of obesity was 11% in women and 15% in men. No
      significant secular trends were observed for WHR, but there was an upward trend
      in prevalence of WHR>0.85 in women. A decreased prevalence of smoking in both
      sexes was observed together with an increase in reported leisure time physical
      activity. No significant secular trends were observed in rates of self-reported
      diabetes, although the risk of diabetes attributable to obesity was 24%.
      CONCLUSION: The results indicate that 25-64-y-olds in the recent survey were more
      overweight and obese than earlier studied MONICA participants. The increase in
      BMI was more pronounced in men while abdominal obesity increased principally in
      women. Although obesity and overweight are clearly important risk factors for
      type 2 diabetes, the number of diabetics remains low and any secular increase is
      not yet apparent.

PMID- 15852046
TI  - Psychosocial working conditions and weight gain among employees.
AB  - OBJECTIVE: To study the associations between psychosocial working conditions and
      weight gain. DESIGN, SUBJECTS AND MEASUREMENTS: Data from postal questionnaires
      (response rate 67%) sent to 40- to 60-y-old women (n=7093) and men (n=1799)
      employed by the City of Helsinki in 2000-2002 were analysed. Weight gain during
      the previous 12 months was the outcome variable in logistic regression analyses.
      Independent variables included Karasek's job demands and job control, work
      fatigue, working overtime, work-related mental strain, social support and the
      work-home interface. The final models were adjusted for age, education, marital
      status, physical strain and body mass index. RESULTS: In the previous 12 months,
      25% of women and 19% of men reported weight gain. Work fatigue and working
      overtime were associated with weight gain in both sexes. Women who were
      dissatisfied with combining paid work and family life were more likely to have
      gained weight. Men with low job demands were less likely to have gained weight.
      All of these associations were independent of each other. CONCLUSIONS: Few work
      related factors were associated with weight gain. However, our study suggests
      that work fatigue and working overtime are potential risk factors for weight
      gain. These findings need to be confirmed in prospective studies.

PMID- 15852047
TI  - Phosphoinositide 3-kinase is required for human adipocyte differentiation in
      culture.
AB  - OBJECTIVE: Phosphoinositide 3-kinase (PI3K) is required for murine adipocyte
      differentiation. However, a recent report concluded that PI3K was not involved in
      the differentiation of human preadipocytes into adipocytes. We have re-examined
      the role of PI3K in human preadipocyte differentiation, enrolling more patients
      and using more adipogenic indices. METHODS: Human preadipocytes, isolated from
      nine patients, were induced to differentiate in the presence or absence of 100 nM
      wortmannin. After 12-15 days, triacylglycerol accumulation and the expression of
      adipogenic markers (fatty acid synthase and adiponectin) were measured. RESULTS:
      A significant inhibition in triacylglycerol accumulation and in the induction of
      fatty acid synthase protein expression was observed, but there was no effect on
      adiponectin protein expression. CONCLUSION: Inhibition of PI3K reduces the
      differentiation of human preadipocytes into adipocytes, suggesting a role for
      this enzyme in the human adipogenic process.

PMID- 15852048
TI  - Polysomnography before and after weight loss in obese patients with severe sleep
      apnea.
AB  - OBJECTIVE: While obstructive sleep apnea (OSA) is strongly related to obesity,
      few studies have examined polysomnographic (PSG) changes with major weight loss.
      We examined the effect of weight loss following laparoscopic adjustable gastric
      banding (LAGB) on the PSG changes in patients with severe OSA. In addition, we
      studied daytime sleepiness, the metabolic syndrome and quality of life (QOL).
      METHODS: A prospective study was conducted of 25 severely obese patients (17 men,
      eight women) with paired diagnostic PSG, biochemical and questionnaire studies,
      the first prior to LAGB and the second at least 1 y later. Subjects with a
      baseline apnea-hypopnea index (AHI) >25/h were included. RESULTS: Subject
      baseline age was 44.7 y, weight 154 kg and body mass index 52.7 kg/m(2). The
      second PSG study was conducted 17.7+/-10 (range 12-42) months after surgery and
      mean percentage of excess loss and weight loss were 50.1+/-15% (range 24-80%) and
      44.9+/-22 kg (range 18-103 kg), respectively. There was a significant fall in AHI
      from 61.6+/-34 to 13.4+/-13, improved sleep architecture with increased REM and
      stage III and IV sleep, daytime sleepiness, as measured by Epworth Sleepiness
      Scale, of 13+/-7.0 to 3.8+/-3.0, and fewer patients requiring nasal continuous
      positive airways pressure (CPAP). There were also major improvements in the
      metabolic syndrome, QOL, body image and fewer symptoms of depression (P<0.05 for
      all). CONCLUSION: Weight loss provides major improvement or resolution of OSA and
      CPAP requirements. It also reduces daytime sleepiness, and improves the metabolic
      syndrome and QOL. LAGB placement should be considered a broadly effective therapy
      for sleep apnea in the severely obese patient.

PMID- 15852049
TI  - Antiobese and hypolipidemic effects of platycodin saponins in diet-induced obese
      rats: evidences for lipase inhibition and calorie intake restriction.
AB  - OBJECTIVE: To investigate how and to what extent platycodin saponin (PS) from
      Platycodi Radix exerts a favorable influence on obesity and hyperlipidemia.
      DESIGN: Sprague-Dawley rats were fed with a high fat (HF) diet for 4 weeks and
      then the animals were treated with 35 or 70 mg / kg of PS for another 4 weeks.
      Changes in body weight and daily calorie intake were measured regularly during
      the experimental period and the degree of linear correlation for the above two
      variables was further analyzed. The in vitro lipase inhibition of each PS
      compound and the in vivo fecal lipid excretion were examined in hope of revealing
      their relationship. The concentrations of hepatic triglyceride and cholesterol in
      serum. RESULTS: The body weight reduction (13+/-4% vs HF control, P<0.05) by PS
      administration was highly correlated to the food intake restriction (Pearson's
      linear coefficient r=0.752, P<0.005). The in vitro inhibition of lipase by each
      isolated compound and mixture of PS were virtually identical. Consequently, the
      fecal TG excretion was increased by 2.1-3.2 folds depending on the dose of PS.
      The serum TG and LDL-cholesterol concentrations were decreased without noticeable
      changes in HDL-cholesterol levels. Concomitantly, the contents of the hepatic TG,
      cholesterol, and the liver surface fat pads were decreased in ubiquity, but no
      noticeable biochemical abnormalities or histological tissue damages were
      observed. CONCLUSIONS: The administration of PS produced profound effects on the
      control of obesity and lipid metabolism, which resulted in LDL-cholesterol
      reduction. PS also caused a remarkable reduction in calorie intake, which was
      highly correlated to the body weight loss. These results suggest that PS has a
      greater role in anti-obesity, hypolipidemia, and liver protection than previously
      thought. Hence, PS could be a potential therapeutic alternative in the treatment
      of obesity and hyperlipidemia.

PMID- 15852050
TI  - Cost-effectiveness of orlistat for the treatment of overweight and obese patients
      in Ireland.
AB  - OBJECTIVE: To assess the cost-effectiveness of orlistat plus a calorie-controlled
      diet compared with a calorie-controlled diet alone for the treatment of
      overweight and obese patients in Ireland. DESIGN: Economic modelling techniques
      using published international efficacy data and Irish cost data were used to
      estimate the cost-effectiveness of orlistat in obese patients when only
      responders to treatment (ie achieve 5% weight loss after 3 months of treatment)
      continue orlistat after 3 months. The model incorporated known relationships
      between weight loss and quality of life (utility) gain, and weight loss and
      reduction in risk of type 2 diabetes (T2DM) to predict the impact of weight loss
      on quality-adjusted-life-years (QALYs) gained and on the onset of T2DM. The costs
      associated with each treatment arm included the acquisition cost of orlistat,
      cost of a calorie-controlled dietary programme and monitoring and treatment costs
      associated with T2DM. An Irish health-care perspective was taken for the
      analysis, based on 2003 costs. SUBJECTS: Weight loss data on 1386 patients from
      five pivotal orlistat clinical trials with at least 12 months duration were
      pooled (two American and three primarily European studies). All the studies were
      randomized, placebo-controlled, multicentre trials with a similar design. The
      inclusion criteria were BMI > or =28 kg / m(2), age > or =18 y, no diagnosed T2DM
      and the ability to lose 2.5 kg in weight during the introductory period.
      MEASUREMENTS: Cost effectiveness was modelled from these data and presented as
      incremental cost per QALY. RESULTS: When orlistat treatment plus a calorie
      controlled diet was compared with a calorie-controlled diet alone, the
      incremental cost per year was euro 478. The number needed to treat (NNT) to gain
      one QALY was estimated to be 35. The incremental cost per QALY gained was within
      the range considered cost-effective at euro 16,954. Sensitivity analysis
      demonstrated an incremental cost per QALY of euro 11,000-35,000 under a variety
      of assumptions. CONCLUSIONS: Our model suggests that orlistat is effective and
      cost-effective in obese patients, if after 3 months of treatment, only treatment
      responders continue treatment.

PMID- 15852051
TI  - Evaluating the use of early hormonal therapy in patients with localised or
      locally advanced prostate cancer.
AB  - This article evaluates the use of early hormonal therapy in patients with
      localised or locally advanced prostate cancer. In patients receiving
      radiotherapy, an overall survival benefit is proven for adjuvant goserelin
      ('Zoladex') in locally advanced disease. Adjuvant to radical prostatectomy,
      castration (goserelin or orchiectomy) has demonstrated an overall survival
      benefit in patients with lymph node metastases. Survival advantages have not yet
      been proven with nonsteroidal antiandrogens, but immediate or adjuvant
      bicalutamide ('Casodex') improves objective progression-free survival in patients
      with locally advanced disease, with certain quality-of-life advantages over
      castration.

PMID- 15852052
TI  - E-mail and oncology: a survey of radiation oncology patients and their attitudes
      to a new generation of health communication.
AB  - Electronic mail (e-mail) is a powerful tool that can greatly enhance
      communication and has numerous potential applications within the medical
      profession. Physician-patient e-mail communication volume is increasing, but
      little research has addressed patient interests and concerns about this now
      commonplace technology. The goals of this study were to review the available
      literature regarding physician-patient e-mail practices, evaluate patient
      interest, assess patient perspectives about how e-mail communication might
      facilitate medical treatment and advice, and determine areas of patient concern
      regarding e-mail communication with their physicians. To this end, a population
      of cancer patients was sent a written survey designed to assess their access to e
      mail and attitudes about physician-patient e-mail communication. We found that
      patients favored e-mail for increased convenience, efficiency, and timeliness
      about general health problems, while it was not favored for urgent matters.

PMID- 15852053
TI  - Pharmacogenomics education: International Society of Pharmacogenomics
      recommendations for medical, pharmaceutical, and health schools deans of
      education.
AB  - Pharmacogenomics would be instrumental for the realization of personalized
      medicine in coming decades. Efforts are evident to clarify the potential
      bioethical, societal, and legal implications of key pharmacogenomics-based
      technologies projected to be soon introduced into the core practice of medicine.
      In sharp contrast, a lack of sufficient attention to educational aspects of
      pharmacogenomics, both for professionals and for society at large, is evident. In
      order to contribute to this discussion, a 'Pharmacogenomics Education Forum' was
      held on October 2, 2004 during the 3rd Annual Meeting of the International
      Society of Pharmacogenomics (ISP) at Santorini, Greece. The participants, members
      of the ISP Pharmacogenomics Education Forum, after deliberate discussions,
      proposed a document of 'Background Statement' and 'Recommendations and Call for
      Action' addressed to Deans of Education at Medical, Pharmaceutical, and Health
      Schools globally. This document has been considered by the education committee of
      the International Society of Pharmacogenomics and the result is presented here.
      We hope that this call would be listened to, and soon followed by beneficial
      action, ultimately leading to enhanced implementation of personalized medicine
      into core medical education and practice.

PMID- 15852055
TI  - Distinct proteomic profiles of amphetamine self-administration transitional
      states.
AB  - In the rat, continuous access to d-amphetamine (d-AMPH) leads to lengthy bouts of
      self-administration, voluntary abstinence, and relapse to self-administration.
      Previous studies have revealed that the progression from psychostimulant self
      administration to abstinence to relapse is mediated in part by the ventral
      hippocampus. Stimulation of the ventral subiculum (vSub) during voluntary
      abstinence from d-AMPH self-administration reinstates self-administration and
      increases nucleus accumbens (NAc) dopamine efflux. Quantitative proteomic
      examination of the hippocampus from rats naive to amphetamine, during a self
      administration session 'Binge', during voluntarily abstinence 'Abstinent', and
      after reinstatement of self-administration 'Relapse', revealed a differential
      proteomic state during abstinence. Actin- and cytoskeletal-related proteins were
      over-represented in the changes occurring during abstinence and suggest a
      decrease in actin filament polymerization. These changes may underlie alterations
      in neuronal tone during abstinence that could affect both neurotransmission and
      behavior. These data provide the first classification of addiction-related
      behaviors based on clustering of quantitative proteomic measurements. .

PMID- 15852056
TI  - Stab wound of the back causing an acute subdural haematoma and a Brown-Sequard
      neurological syndrome.
AB  - OBJECTIVE: To report on an unusual knife stab injury of the thoracic spine,
      causing an acute subdural haematoma (SDH) and paraparesis. SETTING: Department of
      Surgical Neurology, Ward 20, The Royal Infirmary of Edinburgh. CASE REPORT: The
      weapon was a knife, which traversed the mid-thoracic spinal region, causing an
      incomplete spinal cord lesion, which was demonstrated by myelography to be due to
      an SDH. The haematoma was removed at operation. There was a full neurological
      recovery. CONCLUSION: There was no bony injury. The likely cause for the
      development of the SDH was believed to be due to the sudden impingement on the
      spine by the weapon, rupturing small subdural veins.

PMID- 15852057
TI  - Effect of indomethacin on motor activity and spinal cord free fatty acid content
      after experimental spinal cord injury in rabbits.
AB  - STUDY DESIGN: Determination of functional and biochemical parameters as well as
      the effect of specific therapies on these parameters, in the experimental model
      of neurotrauma in rabbits. OBJECTIVE: To assess the effect of indomethacin (0.1
      3.0 mg/kg for 9 days), a potent inhibitor of endogenous prostaglandin synthesis,
      on the motor activity and on the spinal cord tissue concentration of free
      palmitic, stearic, oleic, arachidonic and docosahexaenoic acids in an
      experimental model of a spinal cord injury in rabbits. SETTING: Faculty of
      Medicine, University of Rijeka, Croatia. METHODS: The animals were randomly
      divided into nine experimental groups, four sham and/or vehicle-treated and five
      indomethacin-treated (including one sham-operated and four injured groups).
      Laminectomy was followed by contusion of the spinal cord, using a modification of
      the technique of Albin. Motor activity was controlled daily during the course of
      the next nine postoperation days and scored using Tarlov's system. Spinal cord
      samples from the impact injury site were taken and frozen in liquid nitrogen.
      Total lipids were isolated and purified by a modification of the method of Folch.
      Free fatty acids (FFAs) were separated from the total lipid extract by
      preparative thin-layer chromatography, converted to the corresponding methyl
      esters and identified using gas chromatography, using nonadecanoic acid as the
      internal standard. RESULTS: The concentrations of all analysed free fatty acids
      were increased in the spinal cord after neurotrauma, in comparison to control
      tissues. Treatment of injured rabbits with indomethacin resulted in a significant
      decrease in spinal cord FFAs and exerted a positive effect on neurotrauma-induced
      motor impairment. CONCLUSION: These results indicate a mechanism whereby
      indomethacin protects rabbits from the sequellae of neuronal damage caused by
      trauma, and suggests that it may be beneficial in the therapy of neurotrauma.
      SPONSORSHIP: This work was supported by the Croatian Ministry of Science and
      Technology (project 062019).

PMID- 15852058
TI  - The 'no-touch' method of intermittent urinary catheter insertion: can it reduce
      the risk of bacteria entering the bladder?
AB  - OBJECTIVE: This in vitro model was designed to determine whether using a no-touch
      method for catheter preparation and insertion would affect the degree of
      contamination transmitted to intermittent urinary catheters. SETTING: Northview
      Laboratories, Northbrook, IL 60062, USA. METHODS: This was a parallel
      experimental study conducted in vitro at an independent testing laboratory under
      Good Manufacturing Practices. Six different models of intermittent urinary
      catheter were tested in triplicate, in accordance with the manufacturer's
      Instructions For Use (IFU). Gloved hands were contaminated with a known amount of
      Staphylococcus aureus or Escherichia coli, preparation for insertion was mimicked
      according to the manufacturer's IFU. The number of bacteria transferred to the
      catheter was then quantified using a validated technique. The null hypothesis
      tested was that the bacterial contamination resulting from handling would be the
      same for all of the catheters. The primary outcome measure was the amount of
      bacteria, expressed as colony forming units (CFU), recovered from the catheters.
      The catheter wrappers were sampled to confirm that active transfer of
      microorganisms had taken place and nonhandled samples served as the negative
      controls. RESULTS: For both test organisms, the number of bacteria recovered from
      the catheters was significantly lower (P < 0.05) for the catheters featuring the
      no-touch design (approximately 5 CFU/plate versus 2.1 x 10(2) to 4.4 x 10(2) for
      the traditional hydrophilic catheters). The bacterial recovery from those
      catheters with the no-touch design often fell below the nominal detection limit.
      CONCLUSION: The results of this study allow the null hypothesis to be rejected;
      it can be concluded that the no-touch method provides a significant benefit in
      reducing the potential for external contamination of an intermittent urinary
      catheter. This result supports the recent recommendations for aseptic
      intermittent catheterization promoted within the guidelines issued by the
      European Association of Urologists (EAU).

PMID- 15852059
TI  - Recurrent pulmonary embolism and pulmonary hypertension in chronic tetraplegia.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe an unusual case of progressive
      pulmonary hypertension due to recurrent pulmonary embolism in a chronically
      paralyzed spinal cord injury patient. SETTING: Veterans Administration Hospital,
      West Roxbury, MA, USA. SUBJECT: A 57-year-old man, tetraplegic, sensory
      incomplete and motor complete for 30 years due to a diving accident, complained
      of lightheadedness and shortness of breath intermittently for 7 years.
      Examination during the latest episode revealed anxiety, confusion, respirations
      28 per min, blood pressure 80/60 mmHg, and arterial pH 7.41, P(CO2) 28 mmHg,
      P(O2) 95 mmHg on 2 l of oxygen. A chest film 2 weeks earlier had revealed a right
      sided cutoff of pulmonary vasculature; the current film showed right-sided
      pleural effusion. Review of EKGs showed a trend of increasing right axis
      deviation with recovery and recurrences during the previous 9 years and a current
      incomplete right bundle branch block with clockwise rotation and inverted T waves
      in V1-4. Computerized tomography with contrast material revealed small pulmonary
      emboli, but only in retrospect. The patient died shortly after scanning. AUTOPSY:
      The pulmonary arteries were free of thromboemboli on gross examination but medium
      and small-sized arteries were constricted or obliterated with thrombotic material
      microscopically. The estimated ages of the thromboemboli ranged from days to
      years. The right ventricle was hypertrophied; the coronary arteries were patent.
      CONCLUSION: Recurrent pulmonary emboli resulted in chronic pulmonary hypertension
      and eventual death in a patient with chronic tetraplegia.

PMID- 15852061
TI  - Dopamine receptor contribution to the action of PCP, LSD and ketamine
      psychotomimetics.
AB  - Although phencyclidine and ketamine are used to model a hypoglutamate theory of
      schizophrenia, their selectivity for NMDA receptors has been questioned. To
      determine the affinities of phencyclidine, ketamine, dizocilpine and LSD for the
      functional high-affinity state of the dopamine D2 receptor, D2High, their
      dissociation constants (Ki) were obtained on [3H]domperidone binding to human
      cloned dopamine D2 receptors. Phencyclidine had a high affinity for D2High with a
      Ki of 2.7 nM, in contrast to its low affinity for the NMDA receptor, with a Ki of
      313 nM, as labeled by [3H]dizocilpine on rat striatal tissue. Ketamine also had a
      high affinity for D2High with a Ki of 55 nM, an affinity higher than its 3100 nM
      Ki for the NMDA sites. Dizocilpine had a Ki of 0.3 nM at D2High, but a Kd of 1.8
      nM at the NMDA receptor. LSD had a Ki of 2 nM at D2High. Because the
      psychotomimetics had higher potency at D2High than at the NMDA site, the
      psychotomimetic action of these drugs must have a major contribution from D2
      agonism. Because these drugs have a combined action on both dopamine receptors
      and NMDA receptors, these drugs, when given in vivo, test a combined
      hyperdopamine and hypoglutamate theory of psychosis.

PMID- 15852062
TI  - Wolframin mutations and hospitalization for psychiatric illness.
AB  - Genetic predisposition plays an important role in most common psychiatric
      disorders. The identification of a specific gene associated with a psychiatric
      illness can lead to improved management of the gene-associated disorder.
      Mutations in the wolframin gene are associated with mental illness. Many patients
      with the Wolfram syndrome (WS), who are homozygous or compound heterozygous for
      wolframin mutations, have severe psychiatric symptoms. In WS families, close
      blood relatives, who have a high probability of carrying a single wolframin
      mutation, had a statistically significant excess, over spouse controls, of
      psychiatric hospitalizations, attempted and completed suicides, and self-reports
      of mental illness. Since heterozygous carriers of wolframin mutations are
      relatively frequent in the population according to the general Hardy-Weinberg
      principle, such mutations might be responsible for the illnesses of many
      psychiatric patients. The hypothesis that heterozygous carriers of a wolframin
      mutation are predisposed to psychiatric illness was tested in subjects from 25 WS
      families. In all, 11 relatives who had psychiatric hospitalizations could be
      genotyped through mutation analysis. Eight of these carried the wolframin
      mutation transmitted in their family, significantly (one-sided P=0.0022) more
      than the 3.0 expected if there were no association between psychiatric
      hospitalizations and mutations at this locus. All eight mutation-positive
      subjects had been hospitalized for a major depression. This confirmation of the
      association is not influenced by confounders, undetected stratification, or
      genetic heterogeneity. The relative risk of psychiatric hospitalization for
      depression was estimated to be 7.1 (95% CI 1.9-26.6) for carriers of a single
      wolframin mutation compared to noncarriers.

PMID- 15852063
TI  - Association between 5-HTTLPR genotypes and persisting patterns of anxiety and
      alcohol use: results from a 10-year longitudinal study of adolescent mental
      health.
AB  - The serotonin transporter gene (5-HTT) encodes a transmembrane protein that plays
      an important role in regulating serotonergic neurotransmission and related
      aspects of mood and behaviour. The short allele of a 44 bp insertion/deletion
      polymorphism (S-allele) within the promoter region of the 5-HTT gene (5-HTTLPR)
      confers lower transcriptional activity relative to the long allele (L-allele) and
      may act to modify the risk of serotonin-mediated outcomes such as anxiety and
      substance use behaviours. The purpose of this study was to determine whether (or
      not) 5-HTTLPR genotypes moderate known associations between attachment style and
      adolescent anxiety and alcohol use outcomes. Participants were drawn from an
      eight-wave study of the mental and behavioural health of a cohort of young
      Australians followed from 14 to 24 years of age (Victorian Adolescent Health
      Cohort Study, 1992 - present). No association was observed within low-risk
      attachment settings. However, within risk settings for heightened anxiety (ie,
      insecurely attached young people), the odds of persisting ruminative anxiety
      (worry) decreased with each additional copy of the S-allele (approximately 30%
      per allele: OR 0.77, 95% CI 0.62-0.97, P=0.029). Within risk settings for binge
      drinking (ie, securely attached young people), the odds of reporting persisting
      high-dose alcohol consumption (bingeing) decreased with each additional copy of
      the S-allele (approximately 35% per allele: OR 0.74, 95% CI 0.64-0.86, P<0.001).
      Our data suggest that the S-allele is likely to be important in psychosocial
      development, particularly in those settings that increase risk of anxiety and
      alcohol use problems.

PMID- 15852065
TI  - [State control of knowledge].

PMID- 15852064
TI  - A family-based and case-control association study of trace amine receptor genes
      on chromosome 6q23 in bipolar affective disorder.

PMID- 15852066
TI  - [Orphan drugs and sick patients].

PMID- 15852067
TI  - [Nursing home medicine illuminated].

PMID- 15852068
TI  - [Echocardiography for all children with heart murmurs?].

PMID- 15852069
TI  - [Referral practice and clinical assessment of heart murmurs in children].
AB  - BACKGROUND: Heart murmurs in infants and children are common, and in most cases
      these are physiological murmurs. In a few cases they represent congenital heart
      disease; it is important to detect those few children by referral to paediatric
      cardiologists. MATERIAL: 220 consecutive children with heart murmur were
      investigated prospectively as outpatients in the Children's clinic, Haukeland
      University Hospital from January through December 2001. Referrals were from
      general practitioners (n = 157), paediatricians or residents at the Children's
      clinic (n = 51), and from one community-based paediatrician (n = 12). The purpose
      was to assess the referrals for completeness and judgment before cardiological
      assessment. Our second goal was to see if the paediatric cardiologist could
      differentiate between innocent and pathological murmurs by history and clinical
      assessment only. RESULTS: 22 (10%) of the referred patients had congenital heart
      defects. They had been through a complete clinical assessment by 38.9% of the
      general practitioners and 83.3% by the community-based paediatrician (p =
      0.0001). A conclusion regarding diagnosis before hospital evaluation was reached
      in only 17.8% of the patients by the general practitioners and in 50% by the
      paediatricians (p < 0.0001). The diagnostic accuracy of the clinical evaluation
      by the paediatric cardiologists had a sensitivity of 81.5%, specificity of 98.5%,
      positive and negative predictive values of 88 and 97.5%, respectively. Two
      patients with significant atrial septum defect would have been missed by clinical
      assessment only. INTERPRETATION: Skills in clinical assessment of heart murmurs
      in infants and children can be improved among general practitioners and
      paediatricians in training. Paediatric cardiologists can differentiate between
      physiological and pathologic murmurs by clinical evaluation only.

PMID- 15852070
TI  - [Evaluation of cardiac murmurs in children].
AB  - BACKGROUND: Many normal children have heart murmurs, but most children do not
      have heart disease. Differentiation of innocent murmurs from those due to
      structural heart disease, pathological murmurs, is largely clinical. MATERIAL AND
      METHODS: This review is based upon the authors' own studies and PubMed searches.
      RESULTS: An appropriate history and a properly conducted physical examination can
      identify children at risk of significant heart disease. INTERPRETATION: If a
      murmur cannot clearly be labelled as innocent based on characteristics like sound
      quality, intensity, location and response to posture, then referral to a
      paediatric cardiologist is indicated. Other indications for referral are any sign
      or symptom of cardiovascular disease such as shortness of breath, cyanosis or
      decreased exercise tolerance. In addition, children with syndromes should,
      because of their high risk of congenital heart disease, be referred to a
      paediatric cardiologist for further evaluation.

PMID- 15852071
TI  - [Fabry disease--a diagnostic and therapeutic challenge].
AB  - BACKGROUND: Fabry disease, unlike most other metabolic diseases, is prone to
      familiar and regional clustering because of X-linked inheritance and normal
      fertility in affected men. Affected individuals can be offered intravenous enzyme
      replacement therapy. MATERIALS AND METHODS: In two counties in western Norway
      there are 41 affected individuals, giving a minimum prevalence of the disease of
      1 in 17,000. The patient material is briefly presented. We discuss some of the
      administrative and financial challenges that this type of diseases present in our
      public health system. RESULTS AND INTERPRETATION: The great variability in
      disease expression and severity within and between families delays the diagnosis
      and necessitates a broad clinical follow up of affected persons. A false
      diagnosis is often made (e.g. MS, irritable colon, a psychiatric disorder,
      idiopathic hypertrophic cardiomyopathy, or kidney failure). The follow up regime
      is briefly described, with special emphasis on the practical and financial
      implications of enzyme replacement therapy in Norway.

PMID- 15852072
TI  - [Basic pharmacokinetics--distribution].

PMID- 15852073
TI  - [Nursing home tasks and physician's role].

PMID- 15852074
TI  - [Nursing needs among recipients of community health care].
AB  - BACKGROUND: We aimed at investigating whether disabled old people can get
      sufficient care in residential facilities for the elderly. MATERIALS AND METHODS:
      All residents in our community's care facilities for the elderly in 2001 were
      registered. Those living in their own homes with a substantial need for care were
      also registered. Burden of care was assessed by six items measuring activities of
      daily life and two items measuring cognitive decline. RESULTS: 309 persons were
      registered; mean age was 84. Those living in residential care facilities staffed
      24 hours a day represented the highest average burden of care, though many
      elderly living in their own homes also need a great deal of care. In our
      community, the number of nursing home beds set aside for short-term stays has
      decreased from 24 to 11 over a eight-year period. The burden of care has
      increased since 1992 in nursing homes as well as in other residential care units.
      INTERPRETATION: Group-dwelling unit staffed around the clock can be a good
      alternative to nursing homes for many demented patients. While a high number of
      such units have been built, the local authorities have found it increasingly
      difficult to provide a sufficient number of nursing home beds for short-term
      stays. Most changes observed can be related to the growing number of inhabitants
      above 80 years of age.

PMID- 15852075
TI  - [General practitioners' views on the cooperation with nursing homes].
AB  - BACKGROUND: In addition to the coordination between primary and secondary health
      care, the collaboration between the general practitioner (GP) and the community
      based nursing services is a challenge. While the GPs are responsible for his or
      her list patients' needs, the organisational structure and resource allocation of
      nursing home services is a community-based responsibility. MATERIAL AND METHODS:
      Data on GPs' view on collaborative aspects of nursing home services was collected
      in a cross-sectional questionnaire survey among all Norwegian list-patient GPs in
      2004 (N=1633). RESULTS: Out of the 1637/3338 (48%) responding GPs, 1180 (72%)
      performed community-based services; 462 (37%) of the latter as nursing home
      physicians. Four out of five GPs found physician-based services for their list
      patients satisfactory. The GPs had an influence on the provision of nursing and
      care services in approximately 50% of cases. The less satisfied GPs were less
      frequently informed when their list patients received nursing home beds and less
      frequently asked to contribute patient information when the need for nursing home
      facilities was assessed. These latter GPs were more often of the opinion that GPs
      should play a major role in the decision for home-based versus nursing home
      services. INTERPRETATION: Although there is a potential for improvement in the
      exchange of information between nursing homes and GPs, 80% of the GPs were
      satisfied with physician-based services in nursing homes.

PMID- 15852076
TI  - [Regional geriatric team--a model for cooperation between nursing homes and
      hospitals].
AB  - Few studies describe and evaluate the use of ambulatory geriatric teams in
      nursing homes. This article gives an account of a model in which a
      multidisciplinary group from the local hospital has been visiting 17 communities
      in Norway twice a year for 11 years. The ambulatory geriatric team includes a
      geriatrician, a geriatric nurse, a physiotherapist and an occupational therapist.
      Their aim is to raise the quality of geriatric assessment and care and to enhance
      the cooperation between the hospital and the nursing homes in the communities.
      The team members are doing a comprehensive geriatric assessment of some of the
      patients; they assess cases for further referral, and examine patients with
      declining functioning with a view to rehabilitation. The team provides
      instruction in various aspects of geriatrics to community care professionals.
      Much time is devoted to discussions on problems raised by the staff, such as
      management of patients with dementia-related behavioural problems, and to provide
      feedback to staff-members. The team liaise between hospitals, nursing homes and
      community care services in the communities in order to enhance communication
      between the professionals involved. An evaluation of the team was done on behalf
      of the National Institute of Health through a postal questionnaire which was
      returned by 223 doctors, nurses and allied health care professionals. The results
      indicate that visits by the ambulatory team improve the knowledge of doctors and
      allied professionals about diseases in the elderly; 92% reported that they now
      felt they were doing a better job.

PMID- 15852077
TI  - [Schizophrenia and the self--existential perspectives on comprehension and
      evaluation].
AB  - Schizophrenia remains mainly an enigma for clinicians and researchers, and all
      levels of possible further comprehension should be explored. A fundamental
      characteristic existential perplexity in schizophrenia has significant bearing on
      the patient's suffering and functional decline, and deserves the attention of
      mental health professionals. Early detection, diagnosis and treatment might all
      profit from an explicit focus on the subjective aspects of this disorder. We
      developed a phenomenological and existentially oriented patient-centered
      programme for the diagnostic process and diagnosis mediation in schizophrenia,
      consistently based on self-reported patient experiences. Conventional diagnostic
      criteria in combination with a firm focus on additional fundamental experiential
      alterations constitute a framework that facilitates an open dialogue throughout
      the evaluation between the patient, his or her family and the therapist. The
      programme has been developed, adjusted and applied over five years on some 120
      patients. It has strengthened diagnostic skills, precision and goal-directedness,
      increased the interest in precise evaluation, and deepened the theoretical
      understanding of early diagnosis. It is well accepted by the patients, their
      families and the professionals. This explicit focus on the patients' inner
      reality and experiences seems to vitalise the patient-therapist relationship.

PMID- 15852078
TI  - [Experiences with a special vulvar clinic in Oslo].
AB  - BACKGROUND: Women with longstanding vulvar problems have difficulties finding
      medical care. In 2000, a first Norwegian vulvar clinic was opened at the Olafia
      centre for venereology in Oslo. The initiative was continued in 2003 by a multi
      professional team in the dept. of gynaecology and obstetrics at Rikshospitalet
      University Hospital. METHODS: Medical records from the two Vulva clinics have
      been reviewed in retrospect. RESULTS: During the period 2000 to 2003, a total of
      217 patients had 470 visits to the Olafia clinic, mean age 31.4 years. Vulvodynia
      was diagnosed in 52% of all patients, 30% had a genital infection, 22% a genital
      dermatitis or dermatosis and 21% a primary sexual problem. At the multi
      professional Rikshospitalet vulva clinic, run by specialists in gynaecology and
      dermato-venereology, 141 patients had 206 visits in 2003, mean age 42.5 years.
      Vulvodynia was diagnosed in 38%, 26% had a genital skin condition, 11% primary
      sexual problems, 10% a genital infection, and 10% a gynaecological problem. A few
      patients were healthy controls. The difference in diagnostic groups is related to
      the age of the patients. CONCLUSION: The options for vulvar patients have
      improved in Oslo. Multi-professional cooperation has been achieved in our
      department, which serves as a national referral centre.

PMID- 15852080
TI  - [A different model for general practice education].

PMID- 15852082
TI  - [Revised definition of community medicine?].

PMID- 15852083
TI  - [General practice education--what can we learn from the Netherlands?].

PMID- 15852088
TI  - [Time is crucial in cardiopulmonary resuscitation].

PMID- 15852086
TI  - [Screening for hereditary hemochromatosis?].

PMID- 15852089
TI  - [Wrong about thiazides].

PMID- 15852091
TI  - [Estrogen replacement therapy and breast cancer].

PMID- 15852094
TI  - [COX 2 inhibitors--a further step back].

PMID- 15852097
TI  - [Does conjugated linoleic acid affect the objectivity?].

PMID- 15852098
TI  - [Norwegian Society of Cardiology and international guidelines].

PMID- 15852099
TI  - [Unethical marketing of eye surgery].

PMID- 15852100
TI  - [Medical dialectics].

PMID- 15852101
TI  - The utility of hypercoordination and secondary bonding for the synthesis of a
      binary organoelement oxo cluster.
AB  - A strategy for the preparation of the otherwise difficult to obtain binary
      organometallic oxides containing two heavy main group elements is described and
      exemplified by the synthesis of [(p-MeOC6H4)2Te(OSnt-Bu2OH)2]2.

PMID- 15852102
TI  - Synthesis and structural characterisation of novel linked bis(beta-diketiminato)
      rare earth metal complexes.
AB  - Rare earth metal complexes based on novel linked bis(beta-diketiminato) ligands
      have been prepared via amine elimination and their structural characterisation
      revealed that the linker unit has significant influence on the geometry and
      coordination mode of the ancillary ligand.

PMID- 15852103
TI  - Tuning the intermolecular dative interactions by altering the ligand planarity
      and counter cations in vanadyl(IV) complexes.
AB  - A vanadyl(iv) complex, K2V(O)(dtoym)2, forms polymeric interactions via
      intermolecular dative bonds; the intermolecular dative interaction is tuned by
      changes of the ligand planarity and counter cations of the vanadyl complex.

PMID- 15852104
TI  - Strong enhancement of second-harmonic generation (SHG) response through multi
      chiral centers and metal-coordination.
AB  - The hydrothermal reaction of CdCl2 with L (L =trans-2,3-dihydro-2-(4'-pyridyl)-3
      (3"-cyanophenyl)benzo[e]indole) in the presence of NaN3 and water offers a novel
      route to [Cd(L-N3)2(H2O)2]n, a 1D infinite molecular box with approximate
      dimensions 10.37 x 6.64 e; 1 is shown to display a very strong SHG response that
      is 80 times that observed for urea.

PMID- 15852105
TI  - The capture of dioxygen, carbon monoxide and sulfur dioxide by
      [(PMe2Ph)4Pt2B10H10].
AB  - The metal-metal bond in [(PMe2Ph)4Pt2B10H10], from reaction of [PtCl2(PMe2Ph)2]
      or PMe2Ph with [(PMe2Ph)2PtB10H12], very readily, and readily reversibly, takes
      up atmospheric O2 to give the peroxidic dioxygen-dimetallaborane complex
      [(PMe2Ph)4(O2)Pt2B10H10], which has Pt-Pt 2.7143(3), Pt-O 2.141(4) and 2.151(4),
      and O-O 1.434(6)A. The {Pt2O2} bonding mode is fluxional. Compound irreversibly
      takes up CO to give the bridging-carbonyl-dimetallaborane complex
      [(PMe2Ph)4(CO)Pt2B10H10] which has a CO vector radial to the cluster, with Pt-Pt
      2.7488(3), Pt-C 2.104(6) and 2.113(6), and C-O 1.163(6)A; CO readily displaces O2
      from to give 3. SO2 similarly reacts with either or to give
      [(PMe2Ph)4(SO2)Pt2B10H10], which has tetrahedral sulfur, with Pt-Pt 2.8194(4), Pt
      S 2.350(2) and 2.381(3), and S-O 1.470(8)A and 1.477(9)A.

PMID- 15852106
TI  - Substituent effects of iridium complexes for highly efficient red OLEDs.
AB  - This study reports substituent effects of iridium complexes with 1
      phenylisoquinoline ligands. The emission spectra and phosphorescence quantum
      yields of the complexes differ from that of tris(1-phenylisoquinolinato
      C2,N)iridium(iii)(Irpiq) depending on the substituents. The maximum emission
      peak, quantum yield and lifetime of those complexes ranged from 598-635 nm, 0.17
      0.32 and 1.07-2.34 micros, respectively. This indicates the nature of the
      substituents has a significant influence on the kinetics of the excited-state
      decay. The substituents attached to phenyl ring have an influence on a stability
      of the HOMO. Furthermore, those substituents have effect on the contribution to a
      mixing between 3pi-pi* and (3)MLCT for the lowest excited states. Some of the
      complexes display the larger quantum yield than Irpiq, which has the quantum
      yield of 0.22. The organic light emitting diode (OLED) device based on tris [1-(4
      fluoro-5-methylphenyl)isoquinolinato-C2,N]iridium(iii)(Ir4F5Mpiq) yielded high
      external quantum efficiency of 15.5% and a power efficiency of 12.4 lm W(-1) at a
      luminance of 218 cd m(-2). An emission color of the device was close to an NTSC
      specification with CIE chromaticity characteristics of (0.66, 0.34).

PMID- 15852107
TI  - 1,1,3,3-Tetramethylguanidine-gallane, (Me2N)2CN(H).GaH3: an unusually strongly
      bound gallane adduct.
AB  - The novel adduct 1,1,3,3-tetramethylguanidine-gallane, (Me2N)2CN(H).GaH3, has
      been prepared by the reaction of [(Me2N)2CNH2]+Cl- with LiGaH4 in Et2O solution.
      Its spectroscopic properties indicate a monomeric species with an unusually
      strong coordinate link between the imido function and GaH3, an inference
      confirmed by the crystal structure at 150 K which also reveals significant
      secondary interactions through non-classical N-H...H-Ga bridges. Despite the
      intrinsic strength of the Ga-N bond, however, vaporisation at ca. 310 K occurs
      with partial dissociation, and decomposition via more than one pathway proceeds
      at temperatures >330-350 K to give a variety of products, including the free
      base, Me2NH, H2, and a novel gallium-nitrogen compound composed of a Ga4N4 cubane
      like core bridged on three edges by -N{C(NMe2)2}GaH2- units.

PMID- 15852108
TI  - New cobalt(II) and zinc(II) coordination frameworks incorporating a pyridyl
      pyrazole ditopic ligand.
AB  - The metal-directed assembly of new molecular frameworks incorporating 4-(4
      pyridyl)pyrazole (L), containing non-linear coordination vectors, is presented.
      Three metallo-arrays of types [Co(LH)2(NO3)4], [Co(LH)2(H2O)4][NO3]4.H2O and
      [Zn2(L-H)2Cl2].2EtOH are reported. The cobalt(II) in [Co(LH)2(NO3)4] displays
      distorted octahedral geometry, with the two protonated pyridyl-pyrazole ligands
      coordinated through their pyrazole nitrogen atoms in a trans-orientation; the
      remaining four coordination sites are occupied by nitrate anions. Two internal
      hydrogen bonds occur between each pyrazole NH and the oxygens of adjacent
      coordinated nitrato ligands. Short intermolecular hydrogen bonds also occur
      between the two pyridinium hydrogens and bound nitrate ligands on different
      molecules to yield a two-dimensional hydrogen-bonded array. Two of these arrays
      interpenetrate to form an extended two dimensional layer; such layers stack
      throughout the crystal structure. A second product of type
      [Co(LH)2(H2O)4][NO3]4.H2O exists as two crystallographically independent, but
      chemically similar, forms. In each form, the two protonated pyridyl-pyrazole
      ligands occupy trans positions about the cobalt, with the remaining four
      coordination sites being filled by water molecules to yield a distorted
      octahedral coordination geometry. Intramolecular hydrogen-bonding is observed
      between the two non-coordinated pyrazoyl nitrogen atoms and bound water oxygen
      atoms. The third complex, [Zn2(L-H)2Cl2].2EtOH, contains dimer units consisting
      of two zinc(II) ions bridged by two pyrazoylate groups in which the coordination
      geometry of each zinc approximates a tetrahedron. Each zinc is bound to two
      deprotonated pyridine-pyrazole ligands (L-H), one pyridyl group (from a different
      dimeric unit) and one chloro ligand. Each pyridyl nitrogen thus connects each of
      these zinc dimers to an adjacent dimer unit, forming a three-dimensional network
      containing small voids. The latter are occupied by ethanol molecules which form
      hydrogen bonds to the chloro ligands.

PMID- 15852109
TI  - Structural and spectroscopic studies on mercury(II) tribenzylphosphine complexes.
AB  - The tribenzylphosphine (PBz3) complexes of mercury(II), [Hg(PBz3)2](BF4)2,
      [Hg(PBz3)2(NO3)2] and [HgX(NO3)(PBz3)](X = Cl, Br, I and SCN), have been
      synthesised and their structures determined by single-crystal X-ray
      crystallography. [Hg(PBz3)2](BF4)2 contains [Hg(PBz3)2]2+ cations with linear P
      Hg-P coordination, the first example of a truly two-coordinate [Hg(PR3)2]2+
      complex. The mercury coordination in [Hg(PBz3)2(NO3)2] can be described as
      distorted tetrahedral, with a significant deviation of the P-Hg-P angle from
      linearity as a result of coordination of the nitrate groups. Nitrate coordination
      is also observed in [HgX(NO3)(PBz3)](X = Cl, Br, I), resulting in significantly
      non-linear P-Hg-X coordination. The thiocyanate complex is a centrosymmetric
      thiocyanate-bridged dimer with distorted trigonal-pyramidal mercury coordination
      to the P atom of PBz3, to the S and N atoms of two bridging thiocyanate groups,
      and to the O atom of one nitrate group. For all the nitrato complexes, secondary
      mercury-nitrate interactions (Hg-O 2.7-3.1 A) effectively raise the coordination
      number of the Hg(II) centres to six. High-resolution 31P solid-state NMR spectra
      of the six tribenzylphosphine mercury(II)-complexes, obtained by combining magic
      angle spinning, proton dipolar decoupling and proton-phosphorus cross
      polarization (CP-MAS), have been recorded. The spectra of [Hg(PBz3)2](BF4)2 and
      [HgX(NO3)(PBz3)](X = Cl, Br, I and SCN) exhibit a single line, due to species
      that contain non-magnetic isotopes of mercury, and satellite lines, due to 1J(31P
      199Hg) coupling. The asymmetric unit of [Hg(PBz3)2(NO3)2] contains two molecules
      with four phosphorus environments, resulting in two AB spectra with 2J(31P-31P)
      coupling, due to species that contain non-magnetic isotopes of mercury, and
      satellite lines consisting of two ABX spectra, due to 1J(31P-199Hg) coupling.
      These spectra have been analysed to yield all of the chemical shifts and coupling
      constants involved. A remarkable increase in 1J(31P-199Hg) is observed from
      [Hg(PBz3)2](BF4)2 to [Hg(PBz3)2(NO3)2] as a consequence of the incorporation of
      the nitrate group into the Hg coordination sphere in the latter case. Several of
      the spectra also exhibit broader satellites due to the presence of scalar spin
      spin coupling between 31P and the quadrupolar 201Hg nucleus. Slow-spinning
      methods have been used to analyze the spinning-sideband intensities of the NMR
      spectra, in order to obtain the 31P shielding anisotropy and asymmetry parameters
      Deltasigma and eta. The 199Hg and 31P NMR shielding tensors of PMe3 models of the
      above six compounds have been calculated using relativistic density functional
      theory. The 31P results are in good agreement with experiment and assist in the
      assignment of some of the signals.

PMID- 15852110
TI  - Synergic effect of two metal centers in catalytic hydrolysis of methionine
      containing peptides promoted by dinuclear palladium(II) hexaazacyclooctadecane
      complex.
AB  - The species obtained by the reaction of [Pd2([18]aneN6)Cl2](ClO4)2(where
      [18]aneN6 is 1,4,7,10,13,16-hexaazacyclooctadecane) with AgBF4 have been
      determined by electrospray ionization mass spectrometry (ESI-MS) to be an
      equilibrium mixture of three major types of dinuclear Pd(II) complex cations,
      [Pd2(mu-O)([18]aneN6)]2+, [Pd2(mu-OH)([18]aneN6)]3+ and
      [Pd2(H2O)(OH)([18]aneN6)](3+), in aqueous solution. The hydroxo-group-bridged
      one, [Pd2(mu-OH)([18]aneN6)]3+, is a dominant species, whose crystal structure
      has been obtained. The crystal structure of [Pd2(mu-OH)([18]aneN6)](ClO4)3 shows
      that each Pd(II) ion in the dinuclear complex is tetra-coordinated by three
      nitrogen atoms and one hydroxo group bridge in a distorted square configuration.
      The two Pd(II) ions are 3.09 A apart from each other. The dinuclear Pd(II)
      complex cations [Pd2(mu-OH)([18]aneN6)]3+ and [Pd2(H2O)(OH)([18]aneN6)]3+ can
      efficiently catalyze hydrolysis of the amide bond involving the carbonyl group of
      methionine in methionine-containing peptides with turnover number of larger than
      20. In these hydrolytic reactions, the two Pd(II) ions are synergic; one Pd(II)
      ion anchors to the side chain of methionine and the other one delivers hydroxo
      group or aqua ligand to carbonyl carbon of methionine, or acts as a Lewis acid to
      activate the carbonyl group of methionine, resulting in cleavage of Met-X bond.
      The binding constant of dinuclear Pd(II) complex cations with AcMet-Gly and AcMet
      were determined by 1H NMR titration to be 282 +/- 2 M(-1) and 366 +/- 4 M(-1),
      respectively. The relatively low binding constants enable the catalytic cycle and
      the possible catalytic mechanism is proposed. This is the first artificial mimic
      of metallopeptidases with two metal active centers.

PMID- 15852111
TI  - Subtle reactivity patterns of non-heteroatom-substituted manganese alkynyl
      carbene complexes in the presence of phosphorus probes.
AB  - The non-heteroatom-substituted manganese alkynyl carbene complexes (eta5
      MeC5H4)(CO)2Mn=C(R)C[triple bond]CR'(3; 3a: R = R'= Ph, 3b: R = Ph, R'= Tol, 3c:
      R = Tol, R'= Ph) have been synthesised in high yields upon treatment of the
      corresponding carbyne complexes [eta5-MeC5H4)(CO)2Mn[triple
      bond]CR][BPh4]([2][BPh4]) with the appropriate alkynyllithium reagents LiC[triple
      bond]CR' (R'= Ph, Tol). The use of tetraphenylborate as counter anion associated
      with the cationic carbyne complexes has been decisive. The X-ray structures of
      (eta5-MeC5H4)(CO)2Mn=C(Tol)C[triple bond]CPh (3c), and its precursor [(eta5
      MeC5H4)(CO)2Mn=CTol][BPh4]([2b](BPh4]) are reported. The reactivity of complexes
      toward phosphines has been investigated. In the presence of PPh3, complexes act
      as a Michael acceptor to afford the zwitterionic sigma-allenylphosphonium
      complexes (eta5-MeC5H4)(CO)2MnC(R)=C=C(PPh3)R' (5) resulting from nucleophilic
      attack by the phosphine on the remote alkynyl carbon atom. Complexes 5 exhibit a
      dynamic process in solution, which has been rationalized in terms of a fast [NMR
      time-scale] rotation of the allene substituents around the allene axis; metrical
      features within the X-ray structure of (eta5-MeC5H4)(CO)2MnC(Ph)=C=C(PPh3)Tol
      (5b) support the proposal. In the presence of PMe3, complexes undergo a
      nucleophilic attack on the carbene carbon atom to give zwitterionic sigma
      propargylphosphonium complexes (eta5-MeC5H4)(CO)2MnC(R)(PMe3)C[triple bond]CR'
      (6). Complexes 6 readily isomerise in solution to give the sigma
      allenylphosphonium complexes (eta5-MeC5H4)(CO)2MnC(R')=C=C(PMe3)R (7) through a
      1,3 shift of the [(eta5-MeC5H4)(CO)2Mn] fragment. The nucleophilic attack of
      PPh2Me on 3 is not selective and leads to a mixture of the sigma
      propargylphosphonium complexes (eta5-MeC5H4)(CO)2MnC(R)(PPh(2)Me)C[triple
      bond]CR' (9) and the sigma-allenylphosphonium complexes (eta5
      MeC5H4)(CO)2MnC(R)=C=C(PPh(2)Me)R' (10). Like complexes 6, complexes 9 readily
      isomerize to give the sigma-allenylphosphonium complexes (eta5
      MeC5H4)(CO)2MnC(R')=C=C(PPh2Me)R'). Upon gentle heating, complexes 7, and
      mixtures of 10 and 10' cyclise to give the sigma-dihydrophospholium complexes
      (eta5-MeC5H4)(CO)2MnC=C(R')PMe2CH2CH(R)(8), and mixtures of complexes (eta5
      MeC5H4)(CO)2MnC=C(Ph)PPh2CH2CH(Tol)(11) and (eta5
      MeC5H4)(CO)2MnC=C(Tol)PMe2CH2CH(Ph)(11'), respectively. The reactions of
      complexes 3 with secondary phosphines HPR(1)(2)(R1= Ph, Cy) give a mixture of the
      eta2-allene complexes (eta5-MeC5H4)(CO)2Mn[eta2-{R(1)(2)PC(R)=C=C(R')H}](12), and
      the regioisomeric eta4-vinylketene complexes [eta5-MeC5H4)(CO)Mn[eta4
      {R(1)(2)PC(R)=CHC(R')=C=O}](13) and (eta5-MeC5H4)(CO)Mn[eta4
      {R(1)(2)PC(R')=CHC(R)=C=O}](13'). The solid-state structure of (eta5
      MeC5H4)(CO)2Mn[eta2-{Ph2PC(Ph)=C=C(Tol)H}](12b) and (eta5-MeC5H4)(CO)Mn[eta4
      {Cy2PC(Ph)=CHC(Ph)=C=O}](13d) are reported. Finally, a mechanism that may account
      for the formation of the species 12, 13, and 13' is proposed.

PMID- 15852112
TI  - Induction of B- to Z-DNA transition by copper and zinc complexes with C(15)
      substituted macrocyclic pentaaza ligands.
AB  - The new macrocyclic ligand 15-fluoro-15-methyl-1,4,7,10,13-pentaazacyclohexadecan
      14,16-dione (2) was synthesised and its crystal structure determined together
      with the ones of the known analogues of 2, 15-fluoro-1,4,7,10,13
      pentaazacyclohexadecan-14,16-dione (1) and 15,15-difluoro-1,4,7,10,13
      pentaazacyclohexadecan-14,16-dione (3). The binding behaviour of all three
      ligands to copper and zinc was studied in the solid state. They can bind to the
      metal centre by either triple coordination (N3) with all secondary amines or
      after double deprotonation of the two amides with all five nitrogen atoms (N5).
      The N5 coordination mode is favoured by the presence of one or two fluorine
      substituents at the C(15) position and by a high pH in the case of aqueous
      solutions. Circular dichroism titrations of poly d(GC) with the metal complexes
      showed that only 4 and 5, that is the copper complexes of 1 and 2, induced a
      complete B- to Z-DNA transition. The degree of cooperativity of the transition
      was found to be 3.4 and 7.3 for 4 and 5 respectively. As a possible hypothesis to
      explain this difference, the additional methyl group in 5 compared with 4 may be
      involved in a hydrophobic interaction with the DNA. Ligand 2, the copper complex
      6 of the bis fluoro substituted ligand 3, and the zinc complex 7 of ligand 1 did
      not induce any change in the direction of Z-DNA. In the case of 6, the CD
      spectrum of the DNA actually showed no change at all, indicating that the complex
      was even not interacting with the B form of DNA. Therefore it is assumed that the
      bis fluoro substitution is causing the complex to be in the neutral N5
      coordination mode at the experimental conditions of pH 7. The electrostatic
      contribution together with the shielding effect of the ligand might explain the
      absence of any interaction with the DNA.

PMID- 15852113
TI  - Thermodynamic studies of the binding of bidentate nitrogen donors with
      methyltrioxorhenium (MTO) in CHCl3 solution.
AB  - Methyltrioxorhenium (MTO) adduct formation with bidentate nitrogen donors 2,2'
      bipyridine (bpy), 4,4'-dimethyl-2,2'-bipyridine (Me(2)bpy), 4,4'-di-tert-butyl
      2,2'-bipyridine (tBu2bpy), 1,10-phenanthroline (phen), 5-methyl-1,10
      phenanthroline (5-Mephen), 5-chloro-1,10-phenanthroline (5-Clphen), 4,7-dimethyl
      1,10-phenanthroline (Me2phen) has been studied at different temperatures in CHCl3
      solution. Spectrophotometeric measurements have been carried out to obtain the
      thermodynamic parameters. All complexes are enthalpy stabilized whereas the
      entropy changes counteract the adduct formation. The results are discussed in
      terms of different basicities of the bidentate N-donors.

PMID- 15852114
TI  - Binuclear biscarbene complexes of furan.
AB  - Carbene complexes of chromium and tungsten with a bridging furan substituent were
      synthesized from lithiated furan precursors and metal hexacarbonyls. The
      binuclear biscarbene complexes [(CO)5M{C(OEt)-C4H2O-C(OEt)}M'(CO)5](M = M'= Cr
      (3), W (4)) were obtained as well as the corresponding monocarbene complexes
      [M{C(OEt)-C(4)H3O}(CO)5](M = Cr (1), W (2)). A method of protecting the carbene
      moiety during the metal acylate stage was used to increase not only the yields of
      the binuclear Fischer biscarbene complexes 3 and 4 but to establish a method to
      synthesize analogous mixed heterobinuclear carbene complexes (M = W, M'= Cr (5))
      in high yields. The binuclear biscarbene complexes 3 and 5 were reacted with 3
      hexyne and yielded the corresponding benzannulated monocarbene complexes
      [M{C(OEt)-C14H17O3}(CO)5](M = Cr (6), W(7)). Complex 5 reacted regioselectively
      with the benzannulation reaction occurring at the chromium-carbene centre. The
      major products from refluxing 3 in the presence of [Pd(PPh3)4] were a monocarbene
      ester complex [Cr{C(OEt)-C4H2O-C(O)OEt}(CO)5](8), the 2,5-diester of furan (9)
      and a carbene-carbene coupled olefin EtOC(O)-C4H2O-C(OEt)=C(OEt)-C4H2O-C(O)OEt
      (10). X-Ray structure analysis of 4 and 6 confirmed the molecular structures of
      the compounds in the solid state and aspects of electron conjugation between the
      transition metals and the furan substituents in the carbene ligands were
      investigated.

PMID- 15852115
TI  - Effect of peripheral donor substituents on the binding modes of
      phosphinomethanide ligands. Synthesis and crystal structures of alkali metal
      derivatives of an O-functionalised phosphinomethanide ligand.
AB  - The O-functionalised tertiary phosphine {(Me3Si)2CH}P(C6H4-2-CH2OMe)2 (9) is
      accessible via the reaction of {(Me3Si)2CH}PCl2 with two equivalents of in situ
      generated 2-LiC6H4CH2OMe. Phosphine 9 is readily deprotonated by Bu(n)Li to give
      the lithium phosphinomethanide [[{(Me3Si)2C}P(C6H4-2-CH2OMe)2]Li] (13), which
      undergoes metathesis reactions with the alkoxides MOR [M = Na, K, R = Bu(t); M =
      Rb, R = 2-ethylhexyl] to give the heavier alkali metal phosphinomethanides
      [[{(Me3Si)2C}P(C6H4-2-CH2OMe)2]M]n in good yields [M = Na (14), n= 2; M = K (15),
      Rb (16), n=[infinity]]. Compounds 9, [{(Me3Si)2CH}P(C6H4-2-CH2OMe)2LiBr]2 (10),
      and 14-16 have been studied by X-ray crystallography; in the solid state 14
      adopts a dimeric structure, whereas 15 and 16 crystallise as one-dimensional
      polymers.

PMID- 15852116
TI  - Synthesis and characterization of novel Pd(II) complexes with chelating and non
      chelating heterocyclic iminocarbene ligands.
AB  - The imidazolium salts [3-R1-1-{2-Ar-imino)-2-R2-ethyl}imidazolium] chloride (C-N;
      Ar = 2,6-iPr2C6H3; R1/R2 = Me/Me (a), Me/Ph (b), Ph/Me (c), 2,4,6-Me3C6H2 (d),
      2,6-iPr2C6H3 (e)) react with Ag(2)O to give Ag(I) iminocarbene complexes (C
      N)AgCl (4a-e) in which the iminocarbene ligand is bonded to Ag via the
      imidazoline-2-ylidene carbon atom. The solid-state structures of 4b and 4d were
      determined by X-ray crystallography and revealed the presence of monomeric
      (carbene)AgCl units with Z and E configurations at the imine C=N bonds,
      respectively. Carbene transfer to Pd occurs when compounds 4b-e are treated with
      (COD)PdCl2 to yield bis(carbene) complexes (C-N)2PdCl2 (6b-e) containing two
      kappa1-C bonded iminocarbene moieties. NMR spectroscopic data indicated a trans
      coordination geometry at Pd. This conclusion was supported by an X-ray structure
      determination of 6b which clearly demonstrated the non-chelating nature of the
      iminocarbene ligand system. EXSY 1H NMR spectroscopy suggests that the non
      chelating structures undergo E/Z isomerization at the imine C[double bond, length
      as m-dash]N double bonds in solution. The preparative results contrast our
      earlier report that the reaction between 4a and (COD)PdCl2 results in a chelating
      kappa2-C,N bonded iminocarbene complex (C-N)PdCl2. The coordination mode and
      dynamic behavior of the iminocarbene ligand systems have been found to be
      dramatically affected by changes in the substitution pattern of the ligand
      system. Sterically unencumbered systems (a) favor the formation of kappa2-C,N
      chelate structures containing one iminocarbene moiety per metal upon coordination
      at Pd(II); these complexes were demonstrated to engage in reversible, solvent
      mediated chelate ring-opening reactions. Sterically encumbered systems (b-e) form
      non-chelating kappa1-C iminocarbene Pd(II) complexes containing two iminocarbene
      ligands per metal. Transannular repulsions across the chelate ring are believed
      to be the origin of these structural differences.

PMID- 15852117
TI  - Density functional theory studies on the reagent Ph3PBr2.
AB  - We report density functional theory geometry optimizations at the B3LYP/6
      311G(d,p) level of theory for the title reagent. Four stationary points on the
      molecular potential energy surface were located and characterized. Three of these
      stationary points are energy minima, one a saddle point. The minima correspond to
      the conventional Ph3PBr2 (three-fold Br-P-Br axis with twisted phenyl rings), the
      ion-pair [Ph3PBr]+Br- and a four-coordinated Ph3PBr2 spoke structure that can
      best be described as charge transfer on account of the substantial charge
      transfer from the Ph3P fragment to Br2 (as determined by a standard Mulliken
      population analysis and other considerations). The particular saddle point found
      corresponds to a three-fold Br-P-Br structure with coplanar phenyl rings. Single
      point B3LYP/6-311+g(3d,2p) calculations were done at the stationary point
      geometries in order to investigate possible deficiencies in the basis set.
      Solvent effects for the three solvents water, dichloroethane and cyclohexane were
      modelled using the self consistent reaction field Onsager method at the single
      point B3LYP/6-311+g(3d,2p) level of theory. In the gas phase, the charge transfer
      complex is the most stable of the four; in solution it is the least stable.

PMID- 15852118
TI  - Cationic tetrakis(nucleobase)complexes of PtII as metalloligands and potential
      building blocks for molecular architectures.
AB  - Three cationic tetrakis(nucleobase) complexes of Pt(II) have been synthesized:
      [Pt(Hmhyp-N7)4](NO3)2.H2O 1, [Pt(Hegua-N7)4](NO3)2.2KNO(3).5H2O and trans
      [Pt(Hmcyt-N3)2(Hegua-N7)2](NO3)2 3 (Hmhyp = 9-methylhypoxanthine, Hegua = 9
      ethylguanine, Hmcyt = 1-methylcytosine). The X-ray crystal structure of has been
      determined. All three cationic compounds rapidly react with Hg(II), but gel
      formation prevented an adequate characterization of the products formed. However,
      a Cu(II) adduct of was isolated in crystalline form and characterized
      crystallographically. [{(H2O)Cu(Hmhyp)4Pt}2Cu(ClO4)4)](ClO4)2(NO3)4.6H2O
      crystallizes in a centrosymmetric Cu-Pt-Cu-Pt-Cu chain structure with Cu-Pt
      separations of 2.791(1)A(outside) and 3.8980(9)A(inside). Two of the three Cu(II)
      ions are bound via exocyclic O(6) sites of the Hmhyp nucleobases. At neutral and
      moderate alkaline pH both and form virtually insoluble precipitates, which
      redissolve at strongly alkaline pH to give eventually anionic [Pt(L)4]2- species
      (L = mhyp, egua). Finally, interacts with complementary Hmcyt to give Watson
      Crick associates, as demonstrated by 1H NMR spectroscopy in DMSO-d(6).

PMID- 15852120
TI  - A structural, magnetic and Mossbauer spectroscopic study of an unusual angular
      Jahn-Teller distortion in a series of high-spin iron(II) complexes.
AB  - Single crystal X-ray structures and susceptibility data are described for six
      homoleptic iron(II) complex salts, of 2,6-di(pyrazol-1-yl)pyridine or a 3,3"
      disubstituted derivative of it. Zero field Mossbauer spectroscopic data for four
      of the complexes, and one previously reported analogue, are also discussed. Four
      of these compounds exhibit an unusual angular Jahn-Teller distortion towards C(2)
      symmetry to differing degrees, while the other two exhibit structures close to
      the "ideal" D(2d) symmetry for this ligand set. This structural distortion has
      two components: a twisting of the plane of one ligand relative to the other about
      the N{pyridine}-Fe-N{pyridine} vector, so that the two ligands are no longer
      perpendicular; and a rotation of one ligand about the Fe ion, so that the
      N{pyridine}-Fe-N{pyridine} angle < 180 degrees. Susceptibility data show that all
      the complexes are fully high-spin between 5 and 300 K, but yield an unusually
      wide range of zero-field splitting parameters for the different compounds of
      between 2.6 and 13.4 cm(-1). Magnetostructural correlations suggest that a low
      value of |D| is diagnostic for a high degree of "rotation" distortion. The
      Mossbauer spectra imply that an increased quadrupole splitting might also be
      diagnostic for the presence of the angular distortion.

PMID- 15852119
TI  - 2:2 Fe(III):ligand and "adamantane core" 4:2 Fe(III):ligand (hydr)oxo complexes
      of an acyclic ditopic ligand.
AB  - A bis-hydroxo-bridged diiron(III) complex and a bis-mu-oxo-bis-mu-hydroxo-bridged
      tetrairon(III) complex are isolated from the reaction of 2,6-bis((N,N'-bis-(2
      picolyl)amino)methyl)-4-tert-butylphenol (Hbpbp) with iron perchlorate in acidic
      and neutral solutions respectively. The X-ray structure of the dinuclear complex
      [{(Hbpbp)Fe([mu-OH)}(2)](ClO(4))(4).2C(3)H(6)O (1.2C3H6O) shows that only one of
      the metal-binding cavities of each ligand is occupied by an iron(III) atom and
      two [Fe(Hbpbp)]3+ units are linked together by two hydroxo bridging groups to
      form a [Fe(III)-(mu-OH)](2) rhomb structure with Fe...Fe = 3.109(1)A. The non
      coordinated tertiary amine of Hbpbp is protonated. Magnetic susceptibility
      measurements show a well-behaved weak antiferromagnetic coupling between the two
      Fe(III) atoms, J= -8 cm(-1). The tetranuclear complex [(bpbp)(2)Fe(4)(mu-O)(2)(mu
      OH)(2)](ClO(4))(4)(2) was isolated as two different solvates .4CH(3)OH and
      .6H(2)O with markedly different crystal morphologies at pH ca. 6. Complex
      .4CH(3)OH forms red cubic crystals and .6H(2)O forms green crystalline platelets.
      The Fe(4)O(6) core of shows an adamantane-like structure: The six bridging oxygen
      atoms are provided by the two phenolato groups of the two bpbp(-) ligands, two
      bridging oxo groups and two bridging hydroxo groups. The hydroxo and oxo ligands
      could be distinguished on the basis of Fe-O bond lengths of the two different
      octahedral iron sites: Fe-mu-OH, 1.953(5), 2.013(5)A and Fe-mu-O, 1.803(5),
      1.802(5)A. The difference in ligand environment is too small for allowing
      Mossbauer spectroscopy to distinguish between the two crystallographically
      independent Fe sites. The best fit to the magnetic susceptibility of .4CH(3)OH
      was achieved by using three coupling constants J(Fe-OPh-Fe)= 2.6 cm(-1), J(Fe-OH
      Fe)=-0.9 cm(-1), J(Fe-O-Fe)=-101 cm(-1) and iron(III) single ion ZFS (|D|= 0.15
      cm(-1)).

PMID- 15852121
TI  - Binding energies, vibrations and structural characteristics of small
      polyphosphorus molecules from quantum chemical computations.
AB  - A systematic search for a quick and cost-effective theoretical method suitable
      for simultaneous studies of the structures, spectra and atomization energies of
      polyphosphorus compounds has been performed. It is demonstrated that density
      functional theory in BPW91/cc-pVTZ formulation provides a reasonable description
      of small Pn (n= 2, 3, 4, 6) clusters and PnRm molecules (R = H, C(SiH3) (3), n=
      1, 2; m= 1, 2, 4), close to that achieved by far more expensive coupled cluster
      calculations. In order to assign intrinsic PP bond strengths compliance matrices
      have been calculated. It is shown that compliance constants of PP bonds provide a
      unique tool for assigning individual mechanical bond strengths in small cluster
      systems.

PMID- 15852122
TI  - New structural features in triphenylphosphinesilver(I) sulfanylcarboxylates.
AB  - We investigated the reactions of 1.5 : 1 : 1 mole ratio mixtures of
      triphenylphosphine, silver nitrate and 3-(aryl)-2-sulfanylpropenoic acids
      H(2)xspa in chloroform/water, where in the acid nomenclature, spa = 2
      sulfanylpropenoato and x = p, Clp, mp, diBr-o-hp or f with p = 3-phenyl-, Clp = 3
      (2-chlorophenyl)-, mp = 3-methoxyphenyl-, diBr-o-hp = 3-(3,5-dibromo-2
      hydroxyphenyl)- and f = 3-(2-furyl)-. The compounds [Ag(PPh(3))(Hpspa)](1),
      [(AgPPh3)2(xspa)][x = Clp (2), o-mp (3), p-mp (4), diBr-o-hp (5) and f (6)] and
      [Ag(PPh3)3(Hfspa)](7) were isolated and all except 7 were characterized by IR,
      Raman and FAB mass spectrometry and by 1H, 13C and 31P NMR spectroscopy. Compound
      6 was also characterized by (13)C CP/MAS, and compounds 1 and 6 by (109)Ag NMR
      spectroscopy. The crystal structures of 1, 2, 3, 4.(CH3)2CO, 5, 6.(CH3)2CO and 7
      were determined by X-ray diffraction. has a supramolecular structure based on
      hydrogen bonding between dinuclear units, and all the other complexes adopt
      discrete structures. 2, 3, 4.(CH3)2CO, 5, and 6.(CH3)2CO are tetranuclear, and 7
      mononuclear. The tetranuclear complexes contain the eight-membered coordination
      ring Ag4S2O2 (2, 3, 4.(CH3)2CO, 6.(CH3)2CO) or the twelve-membered ring
      Ag4(CO2)2S2 (5).

PMID- 15852123
TI  - Synthetic, spectroscopic, computational and structural studies of some 13-vertex
      ruthenacarboranes.
AB  - Reduction of 1,2-closo-C2B10H12 followed by treatment with [RuCl2(p-cymene)]2(p
      cymene = C6H4MeiPr-1,4) affords the 13-vertex ruthenacarborane 4-(p-cymene)-4,1,6
      closo-RuC2B10H12, characterised both spectroscopically and, in two crystalline
      forms, crystallographically. Although asymmetric in the solid state, having a
      docosahedral cage architecture with cage C atoms at vertices 1 and 6, this
      species clearly has Cs symmetry on the NMR timescale at room temperature.
      However, the fluctional process in operation can be arrested at low temperature,
      and an activation energy of 43.1 kJ mol(-1) is estimated. A computational study
      of the related species 4-(eta-C6H6)-4,1,6-closo-RuC2B10H12 reveals that the
      fluctionality is due to a double diamond-square-diamond process, first suggested
      by Hawthorne et al for the analogous CpCo species. These calculations yield an
      activation energy of 40.4 kJ mol(-1), in excellent agreement with that derived
      from experiment. Reduction of 1,2-Ph(2)-1,2-closo-C2B10H10 followed by treatment
      with [RuCl2(eta-C6H6)]2 or [RuCl2(p-cymene)]2 yields the analogous species 1,6
      Ph2-4-(eta-C6H6)-4,1,6-closo-RuC2B10H10 and 1,6-Ph2-4-(p-cymene)-4,1,6-closo
      RuC2B10H10, respectively. These C,C-diphenyl compounds were again studied
      spectroscopically and crystallographically, the p-cymene species again showing
      two crystalline modifications. In contrast to their CpCo and Cp*Co analogues all
      three ruthenacarboranes do not undergo isomerisation in refluxing toluene.

PMID- 15852124
TI  - Effects of solvent on the relative stability of mono and di-aluminium aryloxide
      complexes of bipyridines: anomalous behavior of [(tBu)2Al(OPh)]2(mu-4,4-bipy).
AB  - The temperature dependence of the solution equilibrium constants for
      [((t)Bu)(2)Al(OPh)]2(mu-4,4'-bipy)(1a), [((t)Bu)2Al(OPh)](2)(mu-bipetha)(2a,
      bipetha = 1,2-bis(4-pyridyl)ethane), and [((t)Bu)(2)Al(OPh)]2(mu-bipethe)(3a,
      bipethe =trans-1,2-bis(4-pyridyl)ethylene) in C6D6 and CDCl(3) allow for the
      determination of DeltaH and DeltaS for the dissociation of one Al(tBu)2OPh moiety
      from the bridging ligand, i.e., 2[(tBu)2AL(OPh)]2(mu
      L)<==>(K1)2AL(OPh)(tBu)2(L)+[(tBu)2Al(mu-OPh)]2. For compounds and the DeltaH
      values in C6D6[99(2) kJ mol(-1)(2a) and 109(5) kJ mol(-1)(3a)] and CDCl3[115(5)
      kJ mol(-1)(2a) and 139(7) kJ mol(-1)(3a)] were found to be inversely proportional
      with the dielectric constant of the solvent. In contrast, the DeltaH value for 1a
      in CDCl3 is surprisingly small [14.9(7) kJ mol(-1)] and does not fit with the
      trends adopted by the bipetha and bipethe derivatives or the value obtained in
      C6D6[110(2) kJ mol(-1)]. Unlike the other compounds and the C6D6 solutions, the
      CDCl3 solution of 1a allows for the observation of a second equilibrium
      2Al(OPh)(tBu)2(L)<==>(K2)[(tBu)2Al(mu-OPh)]2+2L, for which the DeltaH has been
      determined [4.5(3) kJ mol(-1)]. This result suggests that in CDCl3 bonding of the
      second Al(tBu)2OPh moiety to Al(OPh)(tBu)2(4,4'-bipy)(1b) is stabilized by the
      presence of the first aluminium, which is counter to ab initio calculations that
      predicts the aluminium in Al(OPh)((t)Bu)2(L) should destabilize the Al-N
      interaction with a second Al(tBu)2OPh group. The BDE for dissociation of both
      Al(tBu)2OPh moieties from 1a-3a, and the energy of formation of hydrogen bond
      interactions with CHCl3, has been calculated by ab initio methods, and no unusual
      effects are inherent in 1a.

PMID- 15852125
TI  - Supercritical hydrothermal synthesis, thermal, spectroscopic and magnetic studies
      of two new polymorphs of Mn(SeO3).
AB  - Two new manganese(II) selenite polymorphs with formula Mn(SeO3) have been
      synthesised using supercritical hydrothermal conditions. The crystal structure of
      both compounds (1) and (2) has been solved from single-crystal X-ray diffraction
      data. The structures consist of a three-dimensional framework formed by MnO6
      octahedra and (SeO3)2- selenite anions with trigonal pyramidal geometry. Compound
      (1) shows chains of elongated, corner-sharing MnO6 octahedra. These chains are
      linked alternately by Mn2O10 dimers of edge-sharing octahedra. Conversely,
      compound (2) exhibits MnO6 octahedra sharing edges with three further octahedra,
      giving rise to a complex three-dimensional framework. The IR spectra show the
      characteristic bands of the selenite anion. Studies of luminescence and diffuse
      reflectance spectroscopy, performed at 6 K and at room temperature, respectively,
      have been carried out for both compounds. The Dq and Racah parameters are Dq=
      830, B= 500 and C= 3790 cm(-1) for (1) and Dq= 795, B= 520 and C= 3785 cm(-1) for
      (2). The EPR spectra of both compounds are isotropic with a g-value of 1.99(1),
      which remains unchanged with variation in temperature. Magnetic measurements
      indicate the presence of antiferromagnetic couplings as the major interactions in
      both phases, but with compound (2) exhibiting at low temperature a canting of
      antiferromagnetically aligned spins. The estimated J-exchange parameters are J/k=
      2.2 and -1.93 for (1) and (2), respectively, with J'= -0.87 and -0.55 K.

PMID- 15852126
TI  - Spin crossover of ferric complexes with catecholate derivatives. Single-crystal X
      ray structure, magnetic and Mossbauer investigations.
AB  - Complexes of general formula [(TPA)Fe(R-Cat)]X.nS were synthesised with different
      catecholate derivatives and anions (TPA = tris(2-pyridylmethyl)amine, R-Cat2- =
      4,5-(NO2)2-Cat2- denoted DNC(2-); 3,4,5,6-Cl4-Cat2- denoted TCC2-; 3-OMe-Cat(2-);
      4-Me-Cat(2-) and X = BPh4-; NO3-; PF6-; ClO4-; S = solvent molecule). Their
      magnetic behaviours in the solid state show a general feature along the series,
      viz., the occurrence of a thermally-induced spin crossover process. The
      transition curves are continuous with transition temperatures ranging from ca. 84
      to 257 K. The crystal structures of [(TPA)Fe(DNC)]X (X = PF6-; BPh4-) and
      [(TPA)Fe(TCC)]X.nS (X = PF6-; NO3- and n= 1, S = H2O; ClO4- and n= 1, S = H2O;
      BPh4- and n= 1, S = C3H6O) were solved at 100 (or 123 K) and 293 K. For those two
      systems, the characteristics of the [FeN(4)O(2)] coordination core and those of
      the dioxolene ligands appear to be consistent with a prevailing Fe(III)
      catecholate formulation. This feature is in contrast with the large quantum
      mixing between Fe(III)-catecholate and Fe(II)-semiquinonate forms recently
      observed with the more electron donating simple catecholate dianion. The thermal
      spin crossover process is accompanied by significant changes of the molecular
      structures as shown by the average variation of the metal-ligand bond distances
      which can be extrapolated for a complete spin conversion from ca. 0.123 to 0.156
      A. The different space groups were retained in the low- and high-temperature
      phases.

PMID- 15852127
TI  - Heteroleptic pyrimidine-2-olate and 4,4[prime or minute]-bipyridine copper(II)
      layered metal-organic frameworks with swelling properties.
AB  - One-pot reaction of CuX2 salts (X = NO3, Cl, ClO4, AcO, SO(4)/2), 2
      Hydroxypyrimidine hydrochloride (2-Hpymo.HCl) and 4,4'-bipyridine (4,4'-bpy), in
      H2O : ethanol : ammonia (20 : 10 : 5) solution, leads to isomorphous extended
      layered materials of type [Cu3(mu-OH)2(mu-Cl)2(mu-2-pymo)(mu-4,4'-bpy)3]nXn.mH2O
      (X = NO3 (1a), Cl (1b), ClO4 (1c), AcO (1d), SO(4)/2 (1e)). The single crystal X
      ray crystallographic analysis performed on species exemplifies that it is built
      by 2D [Cu3(mu-OH)2(mu-Cl)2(mu-2-pymo)(mu-4,4'-bpy)3]n(n+) cationic sheets, which
      pack in a staggered fashion, with non coordinated NO3- anions and crystallisation
      water molecules included in the interlayer voids. XRPD studies performed on the
      species show a swelling response along the crystallographic a axis concomitant to
      aliphatic alcohol inclusion. Additionally, we have also studied the magnetic
      properties of , which show that its magnetic behaviour is dominated by the strong
      antiferromagnetic interactions taking place in the Cu3(mu-OH)2(mu-Cl)2 trinuclear
      cores.

PMID- 15852128
TI  - Measuring the metabolome: current analytical technologies.
AB  - The post-genomics era has brought with it ever increasing demands to observe and
      characterise variation within biological systems. This variation has been studied
      at the genomic (gene function), proteomic (protein regulation) and the
      metabolomic (small molecular weight metabolite) levels. Whilst genomics and
      proteomics are generally studied using microarrays (genomics) and 2D-gels or mass
      spectrometry (proteomics), the technique of choice is less obvious in the area of
      metabolomics. Much work has been published employing mass spectrometry, NMR
      spectroscopy and vibrational spectroscopic techniques, amongst others, for the
      study of variations within the metabolome in many animal, plant and microbial
      systems. This review discusses the advantages and disadvantages of each
      technique, putting the current status of the field of metabolomics in context,
      and providing examples of applications for each technique employed.

PMID- 15852129
TI  - Voltammetric detection of organohalides by redox catalysis: improved sensitivity
      by immobilisation within a cubic phase liquid crystal.
AB  - Two combined strategies are reported for improving the sensitivity of
      organohalide detection by redox catalysis. These are, improvement of the second
      order rate constant (k) for catalytic reduction of the organohalide, and
      improvement of the rate of substrate diffusion. Values of k are calculated for
      both alkyl and aryl halides, from slow scan rate cyclic voltammograms in
      homogeneous solution. It is shown that a Zn(ii) porphyrin exhibits higher
      catalytic rates than the previously used Co(ii) porphyrin or Co(i) salen.
      Amperometric and rotating disk electrode studies of electropolymerised films of
      the Zn(ii) porphyrin, reveal that at optimum thickness, mediator-substrate
      reaction and substrate diffusion are the rate limiting steps. Hence,
      immobilisation of the Zn(ii) porphyrin within the more open structure of a cubic
      phase liquid crystal produces an increase in sensitivity of approx. 10 times, and
      lowers the limit of detection by one order of magnitude. The optimised sensor
      responds linearly to seven organohalides in the range 0.1 microM to 1.0 microM
      with a sensitivity of 6.95 A M(-1) cm(-2). Chronoamperometric experiments with a
      microdisk electrode show that the rate of charge transport in the cubic phase
      films (apparent diffusion coefficient, D(E)= 5.65 x 10(-10)+/- 0.11 x 10(-10)
      cm(2) s(-1)) is faster than in the electropolymerised films (D(E)= 3.64 x 10(
      11)+/- 0.02 x 10(-11) cm(2) s(-1)). The variation of D(E) with the concentration
      of Zn(ii) in the cubic phase suggests that diffusion of charge is predominantly
      by electron self-exchange, rather than by physical movement.

PMID- 15852130
TI  - Chemical transformations of alcohols sampled with the use of adsorptive
      enrichment on the carbon adsorbent traps followed by thermal desorption.
AB  - Graphitized carbons, Carbopack X, Carbograph 5TD and Carbotrap B, used to enrich
      samples of C(3)-C(4) alcohols determined in the atmospheric air produce
      experimental artefacts. After thermal desorption, recoveries for alcohols are
      much smaller than unity with a concomitant appearance of aldehydes and ketones on
      chromatograms. Obviously, the adsorbents studied cannot be recommended for
      analysis of alcohols, ketones and aldehydes in the atmosphere. Polymeric
      adsorbents, Tenax TA and Chromosorb 106, do not exhibit such oxidative
      properties.

PMID- 15852131
TI  - Junction-less reference electrode for potentiometric measurements obtained by
      buffering pH in a conducting polymer matrix.
AB  - A reference electrode for potentiometric measurements based on conducting
      polymers (CP) doped with pH buffering ligands is described. Both the CPs and
      doping ligands are selected and adjusted in such a way that possible ionic and
      redox sensitivity is hampered, while the pH buffering property of the CP film is
      exposed. In this way, the electric potential drop at the conducting
      polymer|solution interface is stabilized and close to constant over a certain pH
      range. The electrode behaves as a pseudo-reference electrode in amphiprotic
      solvents or their mixtures, e.g. water-alcohol mixtures. For the first time
      titration of sulfates with lead(ii) in water-methanol solution using two
      "plastic" electrodes, CP-based Pb(2+)-sensitive indicator and CP-based reference
      electrode, is shown. Because the electrode is junction-less it may easily be
      miniaturized and maintained and thus may serve in frontier applications of
      sensors.

PMID- 15852132
TI  - Flow-through optical fiber sensor for automatic sulfide determination in waters
      by multisyringe flow injection analysis using solid-phase reflectometry.
AB  - A software-controlled flow-through optical fiber diffuse reflectance sensor
      capitalized on the implementation of disk-based solid-phase pre-concentration
      schemes in a multisyringe flow injection analysis (MSFIA) set-up is proposed for
      the trace determination of sulfide in environmental waters and wastewaters. The
      fully automated flowing methodology is based on Fischer's coupling reaction of
      sulfide with N,N-dimethyl-p-phenylenediamine (DMPD) in the presence of Fe(iii) as
      oxidizing reagent in a 0.5 M HCl medium. The on-line generated methylene blue dye
      is subsequently delivered downstream to a dedicated optode cell furnished with an
      octadecyl-chemically modified (C(18)) disk, while continuously recording the
      diffuse reflectance spectrum of the pre-concentrated compound. A double
      regeneration protocol is finally executed to warrant minimum background noise and
      negligible baseline. Under the optimized chemical and hydrodynamic conditions,
      the optosensing MSFIA method features coefficients of variation better than
      0.7%(n= 10) at 50 microg l(-1) concentration, a linear working range of 20-200
      microg l(-1) sulfide, a 3sigma(blank) detection limit of 2.9 microg l(-1) sulfide
      and an injection throughput of 8 h(-1) for a pre-concentration sample volume of
      2.9 ml. The interfacing of the robust and versatile multisyringe flow injection
      based optode with a plug-in spectrophotometer furnished with a light emitting
      diode assures the miniaturization of the overall flow analyzer, which is, thus,
      readily adaptable to real-time monitoring schemes. The potential of the
      multisyringe flow method was assessed via the determination of sulfide traces in
      water samples of different complexity (namely, freshwater, seawater and
      wastewater).

PMID- 15852133
TI  - Two-dimensional (2D) correlation coefficient analyses of heavily overlapped near
      infrared spectra.
AB  - Two-dimensional (2D) correlation coefficient analysis is employed to classify and
      characterize spectral variations among heavily overlapped near-infrared spectra
      of pellets and films of three kinds of polyethylene (PE), high-density (HD), low
      density (LD), and linear low-density (LLD) polyethylene, and five kinds of ivory
      signature seals. The sample-sample (SS) 2D correlation maps are used for
      classification while the wavenumber-wavenumber (WW) 2D correlation maps are used
      for determining spectral variation among the above materials. Both correlation
      maps are obtained by multiplying the original data with themselves. It is found
      that the NIR spectra of pellets and films of HD PE are clearly different from
      those of LD PE and LLD PE, while the NIR spectra of five kinds of ivory seals
      yield easily discernable squares in the SS correlation maps. The background
      variation is thought to be behind the differentiation of the PE samples because
      the WW correlation maps do not indicate appearance of new bands. The correlation
      results are compared with those of principal component analysis (PCA). This study
      is a novel application of 2D correlation coefficient analysis which reveals that
      a comprehensive description of demanding spectral systems is achievable by
      utterly simple mathematical means because 2D correlation maps are obtained via a
      single mathematical operation.

PMID- 15852135
TI  - Nickel sulfide fire assay improved for pre-concentration of platinum group
      elements in geological samples: a practical means of ultra-trace analysis
      combined with inductively coupled plasma-mass spectrometry.
AB  - A method was developed for ultra-trace determination of all six platinum group
      elements (PGE) by inductively coupled plasma-mass spectrometry (ICP-MS). With
      involvement of Fe to the fusion charge compositions of the conventional NiS fire
      assay, a whole assay button in water may disintegrate into powder and then be
      dissolved with HCl. The insoluble residue was collected, and dissolved with HCl +
      H(2)O(2) in a sealed Teflon beaker. After the HCl + H(2)O(2) treatment the Os
      signal response is at least 10 times as high as that in HCl medium. With isotopic
      dilution method for determination of Os, all six PGE were analyzed in one sample
      preparation. This method was applied to a series of Chinese PGE certified
      reference materials, GBW 07288 to GBW 07294, and the results were found to be in
      reasonable agreement with the certified values. Limits of detection were assessed
      from the whole chemical procedure and they are 0.17 ng g(-1) for Ru, 0.01 ng g(
      1) for Rh, 0.16 ng g(-1) for Pd, 0.03 ng g(-1) for Os, 0.07 ng g(-1) for Ir and
      0.11 ng g(-1) for Pt. This method of precision (RSD%) was evaluated using two
      reference materials of GBW 07291 and GBW 07294, and it is within the range from
      4.2% to 10.3%.

PMID- 15852134
TI  - Simultaneous detection of [metal(II)-tpen]2+ as kinetically inert cationic
      complexes using pre-capillary derivatization electrophoresis: an application to
      biological samples.
AB  - A high resolution of doubly charged first row transition (Fe, Cu, Zn, Ni, Co, Mn)
      and heavy metal (Pb, Cd, Hg) ions was achieved in capillary electrophoresis (CE)
      with high sensitivity (sub-micromol dm(-3) level), using NN,N'N'-tetrakis(2
      pyridylmethyl)ethylenediamine (TPEN) as a pre-capillary derivatizing agent. The
      non-charged reagent, TPEN, was applied to capillary zone electrophoresis (CZE)
      for the first time. Since complete spatial separation between the complexes and
      the ligand was carried out in a carrier buffer, which was free of TPEN, kinetic
      inertness of metal complexes was necessary for the detection in this pre
      capillary method. All the nine listed metal complexes were detected: Ca(2+),
      Mg(2+), Al(3+), Fe(3+), and Co(3+) complexes were undetectable. This,
      interestingly, suggests that those nine cations form kinetically inert tpen
      complexes without strong charge-charge interactions between the metal ion and the
      ligand. It is expected that the hard-soft-acid-base (HSAB) principle governed the
      kinetics selectivity. With respect to the electrophoretic behavior, the addition
      of chloride ion and methanol to the carrier significantly improved the
      resolution. This is due to the formation of ternary complexes or ion aggregates
      and the solvation effect, respectively. These effects provided a satisfactory
      baseline resolution among the nine metal ions. An application to biological
      samples was demonstrated. Some metal ions in human serum and urine were
      successfully detected in a simple process without the need for deproteinization
      using a non-coated fused-silica capillary because of the differenciation in the
      direction of migration between organic matter and complexes.

PMID- 15852136
TI  - Determination of extractable perfluorooctanoic acid (PFOA) in water, sweat
      simulant, saliva simulant, and methanol from textile and carpet samples by
      LC/MS/MS.
AB  - Methods were developed to quantify the amount of perfluorooctanoic acid (PFOA)
      extracted from textile and carpet samples through contact with water, methanol,
      and sweat and saliva simulants using LC/MS/MS. The limit of quantitation (LOQ)
      for samples extracted in water and sweat simulant is 1 ppb (ng PFOA (g sample)(
      1)) while the limits of quantitation for samples extracted in saliva simulant and
      methanol were 3 ppb and 2.5 ppb, respectively. Method validation results are
      provided for a polyester control textile sample that was extracted in water on
      two different days by different analysts, which gave an overall recovery of 103%
      and standard deviation of 5.3% for 30 analyses. However, for routine application
      of these methods to a large number of sample sets differing in chemical and
      physical compositions, a complete validation for each sample type is not
      practical or possible since control samples for fortifications are often not
      available. Instead, suitable analytical methods and acceptance criteria are
      described which ensure accurate PFOA quantitation in each of the solvent extract
      types. During routine use of these methods, post-extraction spike recoveries for
      the different sample types and solvents are 100 +/- 15% using a dual isotopically
      labeled (13)C-PFOA internal standard to correct for matrix effects. A comparison
      of extraction solvent versus time using a wrist action shaker for textile and
      carpet samples demonstrates that the total extractable amount of PFOA is similar
      for each of the solvent types. However, as expected the rate of extraction in
      water and simulants is significantly less than that of methanol. Finally, a
      comparison of 2 h and 24 h wrist action shaker extractions with a 1.5 h
      pressurized fluid extraction (PFE) in methanol reveals that the 24 h wrist action
      shaker yields the highest results. The 2 h wrist action shaker results are
      similar to those of the 1.5 h PFE extraction.

PMID- 15852137
TI  - Improved detection of low vapor pressure compounds in air by serial combination
      of single-sided membrane introduction with fiber introduction mass spectrometry
      (SS-MIMS-FIMS).
AB  - The use of two methods in tandem, single-sided membrane introduction mass
      spectrometry (SS-MIMS) and fiber introduction mass spectrometry (FIMS), is
      presented as a technique for field analysis. The combined SS-MIMS-FIMS technique
      was employed in both a modified commercial mass spectrometer and a miniature mass
      spectrometer for the selective preconcentration of the explosive simulant o
      nitrotoluene (ONT) and the chemical warfare agent simulant, methyl salicylate
      (MeS), in air. A home-built FIMS inlet was fabricated to allow introduction of
      the solid-phase microextraction (SPME) fiber into the mass spectrometer chamber
      and subsequent desorption of the trapped compounds using resistive heating. The
      SS-MIMS preconcentration system was also home-built from commercial vacuum parts.
      Optimization experiments were done separately for each preconcentration system to
      achieve the best extraction conditions prior to use of the two techniques in
      combination. Improved limits of detection, in the low ppb range, were observed
      for the combination compared to FIMS alone, using several SS-MIMS
      preconcentration cycles. The SS-MIMS-FIMS response for both instruments was found
      to be linear over the range 50 to 800 ppb. Other parameters studied were
      absorption time profiles, effects of sample flow rate, desorption temperature,
      fiber background, memory effects, and membrane fatigue. This simple, sensitive,
      accurate, robust, selective, and rapid sample preconcentration and introduction
      technique shows promise for field analysis of low vapor pressure compounds, where
      analyte concentrations will be extremely low and the compounds are difficult to
      extract from a matrix like air.

PMID- 15852138
TI  - Construction of an electrochemical DNA chip for simultaneous genotyping of single
      nucleotide polymorphisms.
AB  - An electrochemical DNA chip was constructed for simultaneous genotyping of single
      nucleotide polymorphisms (SNPs) using genomic DNA extracted from blood samples.
      This chip consisted of electrodes located on a single piece of substrate and
      allele-specific oligonucleotide probes on the electrodes. As a first application,
      the 4 SNPs (MxA[-88], MxA[-123], MBL[X/Y], and MBL[A/B]), which have association
      with the efficacy of interferon therapy for HCV patient, were genotyped on the
      new DNA chip. Following hybridization of PCR products containing the 4 types of
      fragments, washing, bisbenzimide H33258 (Hoechst 33258) reaction and
      electrochemical analyses, 59 blood samples were genotyped by the chip method
      simultaneously. All procedures were completed within 2 h and the results were
      100% concordant with those by the direct sequence method. The electrochemical DNA
      chip is expected to be a practical tool for SNPs genotyping.

PMID- 15852139
TI  - Analysis of natural flavonoids by microchip-micellar electrokinetic
      chromatography with pulsed amperometric detection.
AB  - Catechins (catechin and other derivatives) are naturally occurring flavonoids
      present in a number of plants and foods. They are also part of numerous
      nutraceutical formulations because they are believed to have antioxidant, cancer
      chemo-preventative, anti-inflammatory and antimicrobial properties. The
      determination of catechins has traditionally been performed by HPLC. However,
      this methodology is both time and sample intensive and generates large amounts of
      organic solvent waste. In the current report, an application of MEKC using a PDMS
      microchip is presented for the analysis of catechins. The system uses pulsed
      amperometric detection for direct analysis of important naturally occurring
      catechins. The effect of pH, surfactant concentration, detection potential and
      signal stability were analyzed. Linear relationships were found between the
      concentration and peak current, with good stability and limits of detection of 8
      [micro sign]M for catechin, epigallocatechin gallate and epicatechin, and 14
      [micro sign]M for epicatechin gallate. Optimum conditions were applied to the
      detection of selected catechins in a commercially available green tea extract
      nutraceutical and the results were compared to HPLC analysis. The analysis using
      microchip micellar electrokinetic chromatography and pulsed amperometric
      detection was completed in 4.5 min, 10 times faster than the HPLC analysis.

PMID- 15852140
TI  - Extraction, interpretation and validation of information for comparing samples in
      metabolic LC/MS data sets.
AB  - LC/MS is an analytical technique that, due to its high sensitivity, has become
      increasingly popular for the generation of metabolic signatures in biological
      samples and for the building of metabolic data bases. However, to be able to
      create robust and interpretable (transparent) multivariate models for the
      comparison of many samples, the data must fulfil certain specific criteria: (i)
      that each sample is characterized by the same number of variables, (ii) that each
      of these variables is represented across all observations, and (iii) that a
      variable in one sample has the same biological meaning or represents the same
      metabolite in all other samples. In addition, the obtained models must have the
      ability to make predictions of, e.g. related and independent samples
      characterized accordingly to the model samples. This method involves the
      construction of a representative data set, including automatic peak detection,
      alignment, setting of retention time windows, summing in the chromatographic
      dimension and data compression by means of alternating regression, where the
      relevant metabolic variation is retained for further modelling using multivariate
      analysis. This approach has the advantage of allowing the comparison of large
      numbers of samples based on their LC/MS metabolic profiles, but also of creating
      a means for the interpretation of the investigated biological system. This
      includes finding relevant systematic patterns among samples, identifying
      influential variables, verifying the findings in the raw data, and finally using
      the models for predictions. The presented strategy was here applied to a
      population study using urine samples from two cohorts, Shanxi (People's Republic
      of China) and Honolulu (USA). The results showed that the evaluation of the
      extracted information data using partial least square discriminant analysis (PLS
      DA) provided a robust, predictive and transparent model for the metabolic
      differences between the two populations. The presented findings suggest that this
      is a general approach for data handling, analysis, and evaluation of large
      metabolic LC/MS data sets.

PMID- 15852141
TI  - Evaluation of the antioxidant activity by flow injection analysis method with
      electrochemically generated ABTS radical cation.
AB  - A Trolox equivalent antioxidant capacity (TEAC) decolourisation assay was adapted
      to a flow injection analysis (FIA) system and a simple and rapid method for
      antioxidant activity evaluation was developed. To avoid the time consuming step
      of 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS) radical cation
      preparation by chemical oxidation of ABTS, as in the original TAEC assay, and
      hence, to shorten the analysis time, the ABTS radical cation was generated on
      line by electrochemical oxidation of ABTS in the flow-through electrolysis cell
      forming a part of the FIA system. The proposed method was optimised with respect
      to a flow rate, injection volume and ABTS radical cation/carrier ratio. Under the
      optimised conditions linear calibration graphs for Trolox were obtained over the
      range 10-100 microM, with a limit of detection 1.6 microM. Good reproducibility
      (relative standard deviation 1.95%) and sample throughput (32 samples per hour)
      were achieved. The developed method was applied to the evaluation of the
      antioxidant activity of pure compounds and samples of some common beverages. In
      both cases a good correlation between the results obtained by the proposed method
      and TEAC values evaluated by the classic TAEC decolourisation assay was obtained
      (r(2)= 0.996 for pure compounds and r(2)= 0.957 for beverage samples).

PMID- 15852142
TI  - Underpotential deposition and anodic stripping voltammetry at mesoporous
      microelectrodes.
AB  - Using the technique of liquid crystal templating a series of high surface area
      mesoporous platinum microelectrodes was fabricated. The underpotential deposition
      of metal ions at such electrodes was found to be similar to that at conventional
      platinum electrodes. The phenomena of underpotential deposition, in combination
      with the intrinsic properties of mesoporous microelectrodes (i.e. a high surface
      area and efficient mass transport) was exploited for the purpose of anodic
      stripping voltammetry. In particular the underpotential deposition of Ag(+),
      Pb(2+) and Cu(2+) ions was investigated and it was found that mesoporous
      microelectrodes were able to quantify the concentration of ions in solution down
      to the ppb range. The overall behaviour of the mesoporous electrodes was found to
      be superior to that of conventional microelectrodes and the effects of
      interference by surfactants were minimal.

PMID- 15852143
TI  - Treatment of bias in estimating measurement uncertainty.
AB  - Bias in an analytical measurement should be estimated and corrected for, but this
      is not always done. As an alternative to correction, there are a number of
      methods that increase the expanded uncertainty to take account of bias. All
      sensible combinations of correcting or enlarging uncertainty for bias, whether
      considered significant or not, were modeled by a Latin hypercube simulation of
      125,000 iterations for a range of bias values. The fraction of results for which
      the result and its expanded uncertainty contained the true value of a simulated
      test measure and was used to assess the different methods. The strategy of
      estimating the bias and always correcting is consistently the best throughout the
      range of biases. For expansion of the uncertainty when the bias is considered
      significant is best done by SUMU(Max):U(C(test result))=ku(c)(C(test result))+
      |delta(run)|, where k is the coverage factor (= 2 for 95% confidence interval),
      u(c) is the combined standard uncertainty of the measurement and delta(run) is
      the run bias.

PMID- 15852144
TI  - Raman spectroscopy of hot desert, high altitude epilithic lichens.
AB  - Twenty-three highly-coloured lichen specimens belonging to the genera
      Candelariella, Aspicilia and Xanthoria from high altitude sites in the Atacama
      Desert, Chile, 2300-4500 metres, have been analysed non-destructively by Raman
      spectroscopy. The vibrational band assignments in the spectra of the specimens,
      which were still attached to their limestone or sandstone substrata, were
      accomplished by comparison with the chemical compositions obtained from wet
      chemical extraction methods. Carotenoids and chlorophyll were found in all
      specimens as major components and the characteristic spectral signatures of
      calcium oxalate monohydrate (whewellite) and dihydrate (weddellite) could be
      identified; chemical signatures were found for these materials even in lichen
      thalli growing on the non-calcareous substrata, indicating probably that the
      calcium was provided here from wind- or rain-borne sources. The Raman spectral
      biomarkers for a variety of protective biomolecules and accessory pigments such
      as usnic acid, calycin, pulvinic acid dilactone and rhizocarpic acid have been
      identified in the lichens, in broad agreement with the chemical extraction
      profiles. The present study indicates that some form of non-destructive taxonomic
      identification based on Raman spectroscopy was also possible.

PMID- 15852145
TI  - Quantitative determination of surface silanol groups in silicagel by deuterium
      exchange combined with infrared spectroscopy and chemometrics.
AB  - Concentration of silanol groups on silica gel surface has been quantitatively
      determined using the deuterium exchange method. Simple and effective procedures
      have been used in pre-sample drying, deuterium exchange and extraction of
      resulting isotopic mixture from the exchange reaction. Each of four silica gel
      samples with varying surface area has been subjected to pre-drying to remove
      adsorbed water and then quantitatively mixed with deuterium oxide in a steel bomb
      for isotopic exchange. The resulting D(2)O/water mixture was then extracted by
      applying high pressure using infrared pellet press. The infrared spectrum of the
      isotopic mixture was measured and the composition was then determined by a
      multivariate calibration model established between infrared profiles of water in
      D(2)O standard mixtures and their composition. The results show that the silanol
      group concentration determined agrees with the values reported in the literature.

PMID- 15852146
TI  - Improved accuracy of on-line heavy water measurement using infrared spectroscopy
      by investigation of signal-to-noise ratio and temperature influences.
AB  - Experimental protocols for the on-line measurement of heavy water concentration
      in nuclear power plants have been established, and important parameters, such as
      the temperature and signal-to-noise ratio, which govern the accuracy of
      measurement, have been studied. The temperature of a sample should be controlled
      tightly because the temperature variation introduces non-linear baseline
      variations and leads to an increase of the partial least squares calibration
      error. Furthermore, the variation in the signal-to-noise ratio of spectra
      sensitively influences the calibration. For reliable prediction, it is critical
      to maintain the signal-to-noise ratio at a certain level. When the sample spectra
      were collected at a higher temperature, it was possible to acquire spectra with
      an improved signal-to-noise ratio and better calibration. In addition, a single
      beam spectrum of water shifts to a lower frequency, and the maximum transmission
      intensity at around 2500 cm(-1)(the heavy water band location) increases at an
      elevated temperature. Overall, an on-line infrared spectroscopic scheme is
      presented for measuring heavy water. The scheme can be applied to an actual
      process without practical difficulties. If the spectra could be collected at
      elevated temperature over 2 min with the use of a high throughput light source,
      the prediction error could reach to 1.0 ppm.

PMID- 15852147
TI  - Determination of polyaromatic hydrocarbons in river water using a sorbent
      consisting of removable octadecyltrimethylammonium ions attached to cation
      exchange silica in conjunction with commercial C18 silica.
AB  - An application that highlights the usefulness of a solid phase extraction sorbent
      having a removable surfactant "stationary phase" is introduced. Polyaromatic
      hydrocarbons (PAHs) efficiently trap on commercially available non-polar sorbents
      (i.e., C(18) silica). However, solvents that are necessary to break strong
      hydrophobic interactions between the analyte and sorbent are harmful and
      incompatible for direct introduction into a reversed phase liquid chromatographic
      setup. In the presented approach, the entire "stationary phase"-analyte
      association is removed, resulting in very efficient elutions with a final extract
      that is mild and reversed phase liquid chromatographic compatible. Commercial
      C(18) silica was placed adjacent to this sorbent to provide more efficient
      trapping of less hydrophobic PAHs. PAHs were preconcentrated from river water and
      were determined using fluorescence detection coupled to HPLC. Detection limits
      for all PAHs examined were in the sub [micro sign]g L(-1) level.

PMID- 15852148
TI  - Separation and preconcentration phenomena in internally heated
      poly(dimethylsilicone) capillaries: preliminary modelling and demonstration
      studies.
AB  - The concept of achieving low-resolution separations in internally heated
      capillary membranes is discussed in terms of controlling the diffusion
      coefficients of volatile organic compounds in poly(dimethylsilicone) membranes in
      space and time. The behaviour of 1,1,1-trichloroethane in polydimethylsilicone
      was used in conjunction with a mixed-physics finite element model, incorporating
      second order partial differential equations, to describe time and spatial
      variations of mass-flux, membrane temperature and diffusion coefficients. The
      model, coded with Femlab, predicted highly non-linear diffusion coefficient
      profiles resulting from temperature programming a 500 [micro sign]m thick
      membrane, with an increase in the diffusion coefficient of approximately 30% in
      the last 30% of the membrane thickness. Simulations of sampling hypothetical
      analytes, with disparate temperature dependent diffusion coefficient
      relationships, predicted distinct thermal desorption profiles with selectivities
      that reflected the extent of diffusion through the membrane. The predicted
      desorption profiles of these analytes also indicated that low resolution
      separations were possible. An internally heated poly(dimethylsilicone) capillary
      membrane was constructed from a 10 cm long, 1.5 mm od capillary with 0.5 mm thick
      walls. Thirteen aqueous standards of volatile organic compounds of environmental
      significance were studied, and low-resolution separations were indicated, with
      temperature programming of the membrane enabling desorption profiles to be
      differentiated. Further, analytically useful relationships in the [micro sign]g
      cm(-3) concentration range were demonstrated with correlation coefficients >0.96
      observed for linear regressions of desorption profile intensities to analyte
      concentrations.

PMID- 15852149
TI  - Determination of nifursol metabolites in poultry muscle and liver tissue.
      Development and validation of a confirmatory method.
AB  - A method is described for the identification and quantitative determination of
      3,5-dinitrosalicylic acid hydrazide (DSH), the marker residue of nifursol
      metabolites in poultry (turkey, broiler) muscle and liver tissue. The method is
      based on the acid-catalysed hydrolysis of tissue-bound metabolites to free DSH
      and in situ derivatisation with 2-nitrobenzaldehyde to the corresponding
      nitrophenyl derivative NPDSH. A structural analogue of DSH, 4-hydroxy-3,5
      dinitrobenzoic acid hydrazide (HBH) was synthesised to serve as an internal
      standard. The analytes were isolated from the matrix by liquid-liquid extraction
      with ethyl acetate. Determination was performed by LC-MS/MS with negative
      electrospray ionisation. The [M - H](+) ions of NPDSH and NPHBH at m/z 374 were
      fragmented by collision induced dissociation (CID) producing transition ions at
      m/z 182, 183 and 226. The transition ions at m/z 182 and 226 were selected for
      monitoring of NPDSH while the transition ion at m/z 183 was selected for NPHBH.
      The method has been validated according to the EU criteria of Commission Decision
      2002/657/EC at 0.5, 1.0 and 1.5 microg kg(-1) in muscle and liver tissue. A
      decision limit (CC(alpha)) was obtained of 0.04 and 0.025 microg kg(-1) in muscle
      and liver, respectively. Similarly a detection capability (CC(beta)) was obtained
      of 0.10 and 0.05 microg kg(-1) in muscle and liver, respectively. The
      introduction of HBH as an internal standard did not lead to a significant
      improvement of the quantitative performance of the method. In fact for liver
      better performance characteristics were obtained when the IS was not taken into
      account. Nevertheless, as a qualitative marker for recovery, HBH could still be
      very useful in the analysis of unknown samples.

PMID- 15852150
TI  - Capillary electrophoretic separation of sugars in fruit juices using on-line mid
      infrared Fourier transform detection.
AB  - Fourier Transform infrared spectroscopy has been coupled to on-line capillary
      electrophoresis (CE) for the separation and detection of natural sugars in orange
      fruit juices. The CE separation electrolyte comprised 50 mM sodium carbonate
      buffer adjusted to pH 12.3 with NaOH. Galactose was selected as an internal
      standard. To ensure tight connections between the custom-made IR-transparent flow
      cell (optical path length was 15 [micro sign]m) and the fused silica capillaries,
      commercially available O-rings were used. The scanner of the spectrometer was
      operated at a HeNe laser modulation frequency of 320 kHz, recording
      interferograms in a double-sided, forward-backward mode with 8 cm(-1) spectral
      resolution. For each spectrum 64 interferograms (512 for the background) were co
      added and a Blackman-Harris 3-term apodization function was performed. A low-pass
      filter at 1828 cm(-1) was inserted in the IR beam to increase the light
      throughput in the spectral region of interest (1800 cm(-1)-900 cm(-1)). Using
      these features a new spectrum could be obtained every two seconds. Sucrose,
      glucose and fructose were structurally identified and quantified in orange juice
      samples. The limits of detection (3S/N) for all analytes were in the low
      millimolar range (0.7-1.9 mM) or, in absolute amounts, the low nanogram range
      (1.5-3.2 ng). The resolution ranged between 1.14 to 3.15 and the RSD of the
      proposed method was 1.8-4.4%.

PMID- 15852151
TI  - Gas-phase radical chemistry in the troposphere.
AB  - Atmospheric free radicals are low concentration, relatively fast reacting species
      whose influence is felt throughout the atmosphere. Reactive radicals have a key
      role in maintaining a balanced atmospheric composition through their central
      function in controlling the oxidative capacity of the atmosphere. In this
      tutorial review, the chemistry of three main groups of atmospheric radicals
      HO(x), NO(x) and XO(x)(X = Cl, Br, I) are examined in terms of their sources,
      interconversions and sinks. Key examples of the chemistry are given for each
      group of radicals in their atmospheric context.

PMID- 15852152
TI  - Models of molecular geometry.
AB  - Although the structure of almost any molecule can now be obtained by ab initio
      calculations chemists still look for simple answers to the question "What
      determines the geometry of a given molecule?" For this purpose they make use of
      various models such as the VSEPR model and qualitative quantum mechanical models
      such as those based on the valence bond theory. The present state of such models,
      and the support for them provided by recently developed methods for analyzing
      calculated electron densities, are reviewed and discussed in this tutorial
      review.

PMID- 15852153
TI  - The development of novel ninhydrin analogues.
AB  - Following its discovery by Siegfried Ruhemann in 1910, ninhydrin rapidly became a
      practical analytical tool. In 1954 it was found to be an important reagent to
      develop fingerprints on porous surfaces. Since its use in forensic chemistry,
      many efforts have focused on improving the reagent. Many of the shortcomings of
      ninhydrin have been met by the synthesis of a variety of ninhydrin analogues.
      This tutorial review provides a short introduction to ninhydrin and highlights
      the different synthetic approaches used in the development of analogues for the
      detection of latent fingerprints.

PMID- 15852154
TI  - Intramolecular dissociative electron transfer.
AB  - Dissociative electron transfers (ET) are reactions in which the ET is associated
      with the cleavage of a sigma bond. Although a rather satisfactory amount of
      information is currently available on the intermolecular and heterogeneous
      dissociative ET reactions, less is known for the corresponding intramolecular
      processes, despite the relevance of these reactions in both chemistry and
      biochemistry. This tutorial review focuses on the most recent developments in
      this area, with particular emphasis on the reactions occurring in well-defined
      Donor-Spacer-Acceptor molecular systems. The goal is to provide the reader with
      the essential background to understand and possibly predict the feasibility and
      rates of these reactions, as well as to stimulate the application of the
      intramolecular dissociative ET concepts and related issues to still unexplored
      molecular systems.

PMID- 15852155
TI  - Attachment of organic layers to conductive or semiconductive surfaces by
      reduction of diazonium salts.
AB  - Surface chemistry is the topic of this tutorial review. It describes the
      electrochemical reduction of aryl diazonium salts on carbon, silicon or metals
      which leads to the formation of an aromatic organic layer covalently bonded to
      the surface. The method which permits such a modification is set forth. The proof
      for the existence of the organic layer is brought forward. The grafting mechanism
      and the covalent bonding between the surface and the aryl group are discussed.
      The formation of mono or multilayers depending on the experimental conditions is
      rationalized. Finally some examples of the possible uses of this reaction are
      given.

PMID- 15852156
TI  - Activity of water in aqueous systems; a frequently neglected property.
AB  - In this critical review, the significance of the term 'activity' is examined in
      the context of the properties of aqueous solutions. The dependence of the
      activity of water(l) at ambient pressure and 298.15 K on solute molality is
      examined for aqueous solutions containing neutral solutes, mixtures of neutral
      solutes and salts. Addition of a solute to water(l) always lowers its
      thermodynamic activity. For some solutes the stabilisation of water(l) is less
      than and for others more than in the case where the thermodynamic properties of
      the aqueous solution are ideal. In one approach this pattern is accounted for in
      terms of hydrate formation. Alternatively the pattern is analysed in terms of the
      dependence of practical osmotic coefficients on the composition of the aqueous
      solution and then in terms of solute-solute interactions. For salt solutions the
      dependence of the activity of water on salt molalities is compared with that
      predicted by the Debye-Huckel limiting law. The analysis is extended to
      consideration of the activities of water in binary aqueous mixtures. The
      dependence on mole fraction composition of the activity of water in binary
      aqueous mixtures is examined. Different experimental methods for determining the
      activity of water in aqueous solutions are critically reviewed. The role of water
      activity is noted in a biochemical context, with reference to the quality,
      stability and safety of food and finally with regard to health science.

PMID- 15852157
TI  - [An important step in the right direction. Improved preoperative diagnostics--a
      medical and economic necessity].

PMID- 15852159
TI  - Advances and gaps in ocular allergies.

PMID- 15852158
TI  - [The scientific priorities: recognized or silenced?].

PMID- 15852160
TI  - [Advances and gaps in ocular allergies].

PMID- 15852161
TI  - [Prophylactic antibiotics in postoperative endophthalmitis].

PMID- 15852162
TI  - [Corneal biomechanics].
AB  - OBJECTIVE: To review the corneal biomechanic concepts and to analyse, clarify and
      understand their relevance in refractive surgery. MATERIALS AND METHODS: A
      literature review has been done using different databases. RESULTS: Corneal
      biomechanic concepts are not new and are applied implicitly in numerous surgical
      procedures. Their origin is related to tonometry studies, but they gained in
      popularity when they were linked to the treatment of keratoconus, a pathology in
      which the mechanical properties of the cornea are altered. Factors determining
      corneal stability were thus defined. Corneal biomechanics have also been used
      following refractive surgery to study post-operative keratectasia and to improve
      ablation patterns, which ignores the corneal response. The new ablation systems
      need to include the biomechanical factors, which motivate research conducted in
      physical-mathematical models and in corneal wound healing, improving our
      knowledge about the corneal biomechanical response. CONCLUSIONS: The corneal
      biomechanic concepts have gained in popularity with the advent of refractive
      surgery, although they did exist previously. Their relevance is linked to
      improvements in the ablation systems used in an attempt to obtain more accurate
      and reliable results.

PMID- 15852163
TI  - [Use of optical coherence tomography to study variations of normal parameters
      with age].
AB  - PURPOSE: To determine by Optical Coherence Tomography (OCT) the variation of a
      variety of measurable parameters (macular thickness, retinal parapapillary fiber
      layer thickness and optic disc morphology) with age. METHOD: We carried out OCT
      in 40 normal subjects (80 eyes) aged between 20 and 60 years, divided into 4
      groups according to the age decades. RESULTS: Statistically significant
      differences were found in the macular thickness in the comparative study groups
      but the differences varied according to the sector assessed; the superior outer
      sector (p=0.00), temporal outer sector (p=0.01), temporal inner sector (p=0.04),
      nasal inner sector (p=0.03) and inferior inner sector (p=0.00). In the study of
      retinal parapapillary fiber layer thickness, statistically significant
      differences were found between groups in the inferior sector only (p=0.04). No
      statistically significant differences were found between groups in the study of
      optic disc morphology. CONCLUSIONS: Both the macular thickness and the nerve
      fiber layer in the inferior sector decrease with age. These differences in
      thickness are statistically significant between the extremes of age decades.

PMID- 15852164
TI  - [Serum IGF-I levels in retinopathy of prematurity. New indications for ROP
      screening].
AB  - OBJECTIVE: To determine the IGF-I serum levels in premature infants with the
      objective of being able to use these levels as an indicator of the need for
      exploration in a screening program for retinopathy of prematurity (ROP). METHODS:
      This was a comparative study in which IGF-I levels were measured in every
      infants' serum during the first exploration in the 4 to 6 postnatal weeks. The
      degree of ROP and a variety of morbidity factors were evaluated, including the
      presence of intraventricular haemorrhage, sepsis, need for blood transfusion and
      the number of days of mechanical ventilation. RESULTS: The average IGF-I values
      during the first 4 to 6 postnatal weeks were lowest in the ROP cases (10.75
      microg/L SD 16.053) while the NO-ROP cases yielded higher values (29.75 microg/L,
      SD 13.022). The Mann-Whitney U test showed a value of P for the IGF-I values of
      0.004, indicating significant differences between the groups with or without ROP.
      CONCLUSIONS: The low IGF-I serum levels in ROP infants in comparison with the NO
      ROP cases, suggest that this marker could be used as an indicator in the
      screening for ROP.

PMID- 15852165
TI  - [Ahmed drainage device implant. Our experience between 1995 and 2003].
AB  - PURPOSE: To evaluate the indications, results and complications of the Ahmed
      drainage device implanted between January 1995 and December 2003. MATERIALS AND
      METHODS: A retrospective study of 70 eyes in 65 patients. We analysed: the
      indications for surgery; the preoperative intraocular pressure (IOP), the
      postoperative IOP at 1 and 3 months, 1, 2 and 3 years after surgery; and the
      short and long term postoperative complications. We defined an absolute success
      as an IOP between 5 and 21 mmHg without glaucoma medications, relative success
      the same IOP levels whilst taking glaucoma medications and failure as an IOP of
      less than 5 and more than 22 mmHg. RESULTS: The most frequent indications for use
      of the drainage device were: neovascular glaucoma (45.7%), no response to other
      glaucoma surgery (20%), aphakic glaucoma (10%) and traumatic glaucoma (8.5%).
      Mean preoperative IOP was 39 mmHg. Mean postoperative IOP was: 19.7 mmHg (1
      month), 21.6 mmHg (3 months), 19.6 mmHg (1 year), 18 mmHg (2 years) and 18.6 mmHg
      (3 years). The most frequent early complications were athalamia and hiphema. The
      most frequent late complications were tube or body valve extrusion and fibrotic
      reaction around the valve. CONCLUSIONS: Both the indications and success rates
      are similar to those previously reported. Visual acuity assessment is not of
      value in this group of patients because of their multiple associated ophthalmic
      pathologies.

PMID- 15852166
TI  - [Intraocular lenses with blue light filter].
AB  - PURPOSE: To evaluate if a SN60AT <<Natural>> IOL (Alcon) with IMPRUV filter
      (Alcon) offers any advantage in patients having cataract surgery, as compared
      with Acrysof SA60 IOL (Alcon). METHODS: This was a prospective analytical study.
      We studied sixty-four eyes from 32 patients with cataracts. After a random
      assignment, phacoemulsification with the implant was performed using the Acrysof
      SN60AT tinted lens in one eye and Acrysof SA60 in the other. A variety of
      variables was subsequently assessed: contrast sensitivity with a CSV 1000E test,
      colour perception through a Farnsworth 25 test and subjective measures by a
      patient survey. Differences between the groups were assessed statistically.
      RESULTS: The contrast sensitivity results were obtained for 3, 6, 12 and 18
      cycles per degree (cpd) frequencies under scotopic conditions, with better
      results obtained following the use of SN60AT: 0.75 (CSV 1000E test units) for 3
      cpd, 0.86 for 6 cpd, 0.54 for 12 cpd and 0.35 for 18 cpd. The differences were
      statistically significant between the two groups for 3 cpd and 6 cpd. A total of
      62.5% of patients using a tinted lens and 50% with SA60 achieved good results in
      the Farnsworth test; 12.5% and 21% had fair results and 25% and 28.1%
      respectively had poor results. CONCLUSIONS: We obtained an improvement in favour
      of the tinted lens for all frequencies, with this being statistically significant
      at lower frequencies (3 and 6 cpd). No significant differences in the Farnsworth
      test performance or in the patient survey were found. The tinting provided by the
      IMPRUV filter brings an increase in contrast sensitivity without affecting colour
      perception.

PMID- 15852167
TI  - [Bardet-Biedl syndrome].
AB  - We report a case of Bardet-Biedl syndrome. CASE REPORT: A nine-year-old boy was
      having problems of recent loss of vision when in the dark. He was born with
      polydactyly in the feet for which he had surgery performed when he was seven
      weeks old. Mental retardation was significant and his vision was poor. Clinical
      and electrophysiologic examinations showed the existence of a pale optic disc and
      loss of the electroretinographic response under scotopic and photopic conditions.
      DISCUSSION: Based on the history, presentation, ophthalmic clinical examination,
      obesity, mental retardation and dental alterations, the patient was diagnosed
      with Bardet-Biedl syndrome. Current references are reviewed.

PMID- 15852168
TI  - [Central serous chorioretinopathy as a complication of epitheliopathy under
      treatment with glucocorticoids].
AB  - CASE REPORT: We present cases of two patients who were examined in our department
      with the diagnosis of epitheliopathy following treatment with oral and topical
      glucocorticoids. They were referred because of loss of visual acuity. The
      ophthalmic examination established the diagnosis of central serous
      chorioretinopathy and it was decided to stop treatment with glucocorticoids.
      DISCUSSION: The pathogenesis of the central serous chorioretinopathy is still
      imprecisely known, but it has been related to several situations characterized by
      exposure to high levels of endogenous or exogenous glucocorticoids. Both of these
      cases provide more evidence of the potential association between corticosteroids
      and the acute manifestations of central serous chorioretinopathy.

PMID- 15852170
TI  - [XIX international congress of ophthalmology. (New Delhi - India, 1962)].

PMID- 15852169
TI  - [The trachoma agent. Historical notes].

PMID- 15852171
TI  - [The neck -- a sonographically interesting region for many medical fields].
AB  - The soft tissues of the neck can be examined at the highest resolution with
      ultrasound probes of high frequencies due to their superficial position. There
      are many clinically important diagnostic issues concerning the thyroid gland, the
      parathyroid, lymph nodes, vessels of the neck, salivary glands and other
      structures of the field of ENT and even the nerves of this region. Numerous
      different medical departments therefore work in this field either together or I a
      parallel fashion. In addition to different sub-specialties of internal medical
      and surgical departments, radiologists, neurologists, ENT doctors, gnathologists
      and radio-oncologists are all active here. Even intensive care personnel and
      anaesthesiologists use ultrasound for sonographically guided punctures. It is
      therefore obvious that the cervical region is of special importance for an
      interdisciplinary journal, constituting a large part of publications. In the last
      2 (1/2) years, we published two articles about cervical lymph nodes , eight
      concerning the topic of vessels , two articles about salivary glands and three
      dealing with the parathyroid glands . The present issue again contains three
      publications concerning this area, characteristically from three different
      medical specialties, each of great significance for various medical fields. An
      important article deals with deQuervain thyroiditis . Albeit this is not a common
      disease, any clinician working on the cervical region should be well aware of
      this entity, as the patients concerned often go through a medical "odyssey" with
      different specialists before the right diagnosis is made. An important addition
      to sonographical interventional techniques is percutaneous instillation therapy
      for focal autonomous adenomas of the thyroid : it is fast acting and effective,
      representing a genuine therapeutic alternative to surgery or radioactive iodine
      treatment in many cases. The case report on a - fortunately non-permanent -
      partial laryngeal necrosis resulting from the instillation of 96 % alcohol
      demonstrates the potential damage an established method can cause if applied
      without expertise. It is therefore mandatory to be aware of potential side
      effects and carry out the intervention proficiently, strictly keeping in mind the
      indication for therapy. A further case report demonstrates in an impressive way
      the importance of cervical sonography for the detection and landmarking of
      parathyroid adenomas. The fact that the author is a surgeon might serve as valid
      proof, as the surgery of parathyroid glands almost solely depended on the
      experience and the explorative skill of the surgeon until recently.

PMID- 15852172
TI  - De Quervain's subacute thyroiditis -- colour Doppler sonography findings.
AB  - AIM: De Quervain's subacute nonsuppurative thyroiditis has been well
      characterised clinically: there usually is pain in the region of the thyroid due
      to local pressure. Typically, the patient feels generally ill with fever. Signs
      of inflammation (raised ESR and CRP) are measurable laboratory parameters.
      Occasionally, there is transient hyperthyroidism followed by hypothyroidism.
      Little data is available on the vascularisation of the thyroid in this clinical
      entity. PATIENTS AND METHODS: Twenty-one patients with confirmed De Quervain's
      subacute thyroiditis were investigated and the findings were analysed
      retrospectively (clinical features, sonography, cytology in some cases).
      Ultrasound devices (Siemens Elegra and Acuson Sequoia) with 7 and 12 MHz
      ultrasound transducers and modern technology (harmonic imaging, panorama imaging
      and sensitive colour Doppler units with standardised instrument settings) were
      used. RESULTS: The structures of the thyroid was found to be inhomogeneous. The
      hypoechoic to nonechoic areas corresponded to the inflamed areas. An alteration
      in the morphology and topographic distribution was observed in the course of the
      illness. Normal or slightly increased vascularisation in the echogenically
      "healthy" regions of the thyroid were found in colour Doppler sonography. The
      peak systolic velocity (PSV) in the afferent arteries (superior and inferior
      thyroid arteries) was in the normal range (< 40 cm/s). The hypoechoic/nonechoic
      map-like areas showed a reduction or complete absence of blood flow. CONCLUSION:
      De Quervain's subacute thyroiditis can be conclusively diagnosed by sonography in
      more than 90 % of cases based on the history, typical clinical features and
      clinical test parameters indicating signs of inflammation. Colour Doppler
      sonography can be useful in differential diagnosis of unclear cases.

PMID- 15852174
TI  - Ultrasound-guided anaesthesia of the axillary brachial plexus: efficacy of
      multiple injection approach.
AB  - AIM: High resolution ultrasound is a new method for detecting anatomical
      structures in the axilla. The visualisation of nerves can improve the quality of
      nerve blocks. The aim of our study was to investigate the feasibility of hand
      held ultrasound to perform sonographically guided blockades of the axillary
      plexus. METHOD: We investigated 46 patients routinely scheduled for forearm and
      hand surgery (ASA physical status I-IV, age range 19 - 89 years, mean 47). The
      axilla was examined using a handheld ultrasound system with a 10 MHz linear array
      probe. The median, ulnar, radial and musculocutaneus nerve were visualised by
      ultrasound. Selective nerve blockade was performed under sonographic guidance.
      Real time monitoring of the local anaesthetic spread was performed. Time required
      to perform the block and onset times of anaesthesia were documented. RESULTS:
      Complete anaesthesia of the brachial plexus was achieved in all cases. The
      average time to perform the block was 5 minutes (SD 2 min). Onset time for the
      block was 7 minutes (SD 3 min). CONCLUSION: Performing axillary nerve blockade
      using ultrasound guidance provides excellent anaesthesia and fast onset times.

PMID- 15852173
TI  - [Detection of liver lesions by contrast-enhanced ultrasound -- comparison to
      intraoperative findings].
AB  - AIM: Evaluation of b-mode and colour-duplex imaging, contrast-enhanced ultrasound
      (CEUS) and CT for the detection of liver lesions in comparison to intraoperative
      and histological findings. METHODS: Before laparotomy, 100 patients with
      suspected liver lesions were prospectively examined with b-mode and colour-duplex
      imaging followed by contrast-enhanced ultrasound (SonoVue) and CT-scan. Patients
      with nonresectable tumours (n=44) were excluded from the analysis. The diagnostic
      findings of 56 patients who displayed liver lesions were compared to the
      intraoperative and histological findings. RESULTS: CEUS enhanced the sensitivity
      for the number of detected lesions from 53 % (b-mode) to 86 % (CEUS) (p = 0.001),
      while CT-scan reached 76 %. The specificity of the three methods differed only
      slightly (87 % to 89 %). Contrast agents lead to an improvement in the results of
      ultrasound, particularly in cases of nodular metastases smaller than one
      centimeter (n = 7), after adjuvant chemotherapy (n = 4), near the surface (n = 6)
      and in lesions situated around the Lig. teres (n = 6). CONCLUSIONS: CEUS leads to
      a significant improvement in the detection of liver lesions. For patients after
      adjuvant chemotherapy as well as for cases of small nodular metastases a CEUS
      should be carried out as a routine.

PMID- 15852175
TI  - [Functional ultrasound examination of the posterior cruciate ligament -- a new
      method of detecting ligament instability in the knee joint].
AB  - AIM: Detection of injuries to the posterior cruciate ligament (PCL) is difficult
      and dismissed in many cases. Here we introduce dynamic ultrasound examination as
      a safe and reproducible method to detect a PCL-insufficiency with or without
      fixed posterior tibia position and combined injuries to the cruciate ligament
      complex. PATIENTS AND METHOD: Dynamic ultrasound examination in a modified
      technique to Schwarz et al. was performed on 20 patients with a PCL-insufficiency
      (group 1) and 20 patients with an anterior cruciate ligament (ACL) insufficiency
      (group 2). Comparing both knee joints, we measured the resting value (RV),
      ventral translation value (VT) and dorsal translation value (DT). Mean value,
      standard deviation in mm and t-test for unpaired values were compared with each
      group and a healthy control population. RESULTS: In group 1 we could distinguish
      patients with fixed posterior position (PCL (mfix)) who showed a pathological
      dorsal RV (2.96 mm) from patients without fixation (PCL (ofix),: RV = 0.7 mm). DT
      was significantly prolonged (PCL (mfix): 6.4 mm; PCL (ofix): 5.6 mm) compared to
      healthy individuals. Group 2 showed a pathological RV (2,38 mm) and a significant
      prolonged VT (4.19 mm). 10 patients in this group had a spontaneous ventral tibia
      translation (RV: 3.7 mm) and 10 patients with ACL insufficiency showed a normal
      resting value (RV: 0.88 mm). CONCLUSION: Dynamic ultrasound examination allows us
      to distinguish between isolated ACL- or PCL-insufficiency and combined injuries
      of the cruciate ligament complex using a standardized flow sheet. PCL
      insufficiency therefore can be separated into the entities of fixed posterior and
      partly reducible instability.

PMID- 15852176
TI  - ["White bowel". A sonographic sign of intestinal lymph edema?].
AB  - AIM: We recently introduced the term "white bowel" to describe the hyperechoic
      appearance of the bowel wall found in a patient with HIV-associated enteropathy.
      The aim of this study was to describe changes of the bowel wall and to
      demonstrate possible causes of this phenomenon. PATIENTS AND METHODS: 10 patients
      identified as showing this phenomenon were enrolled in this study. The ultrasound
      examinations of the patients were re-evaluated with special regard to the
      echogenicity of the different layers of the bowel wall, to mesenteric lymph
      nodes, and to thrombosis of the mesenteric vein. RESULTS: Diagnosis in these 10
      patients included: HIV-associated enteropathy aggravated by Mycobacterium avium
      intracellulare infection (n = 3); endemic coeliac disease and complications
      arising from T-cell lymphoma (n = 2); carcinoma of the small and large intestine
      (n = 3); Whipple's disease (n = 2). Sonography typically showed echogenic
      thickening of the wall of the small intestine -- mainly of the mucosal layer.
      Enlarged mesenteric lymph nodes (with both hypoechoic and occasionally
      hyperechoic appearance) were present in the majority of cases. In 3 cases,
      mesenteric vein thrombosis was also demonstrable. CONCLUSION: The "white bowel"
      was found in patients with different diseases. Most of the patients showed
      enlargement of the mesenteric lymph nodes. Lymph oedema of the bowel wall
      probably constitutes the main reason for this phenomenon.

PMID- 15852177
TI  - Feto-amniotic shunting -- experience of six centres.
AB  - AIM: Foeto-amniotic shunting is an ultrasound-guided, therapeutic intervention
      for drainage of persistent intracavital fluid retention in severely affected
      foetuses with a high risk of mortality. In order to weigh up the comparatively
      high risk of intervention against the possible benefit, we evaluated the value of
      different indications, the complication rate and the time span of drains in situ.
      PATIENTS AND METHODS: We made a survey of all level III ultrasound centres of
      German-speaking countries from 1993 to 2001. Six level III centres returned the
      questionnaire: forty-seven foeto-amniotic shunting procedures were performed in
      30 foetuses [megacystis in 18 foetuses (three of these with urinary ascites),
      hydrothorax in eight foetuses, hydronephrosis in two foetuses, cystic adenomatoid
      malformation of the lung in one foetus, ovarian cyst in one foetus]. RESULTS: The
      median gestational age at time of shunting was 23.5 (range 16 - 33) weeks, at
      time of delivery 35 (range 23 - 41) weeks. The median time span of drains in situ
      was 19 (range 0 - 170) days. Altogether 18 of 30 foetuses (60 %) had a benefit of
      foeto-amniotic shunting. CONCLUSION: The best possible selection of pregnancies
      which might profit from foeto-amniotic shunting is required. The decisive
      criteria are the underlying defect as well as the severity and progression of the
      disorder.

PMID- 15852178
TI  - Complications of ultrasound guided percutaneous ethanol injection therapy of the
      thyroid and parathyroid glands.
AB  - OBJECTIVES: Since 1990 percutaneous ethanol injection therapy (PEIT) has been
      applied clinically as a treatment strategy for focal and diffuse autonomy of the
      thyroid, for cystic lesions and for ablation of parathyroid hyperplasia (PEA).
      There are some additional indications currently under consideration as for
      example inoperable advanced cancer of the thyroid. Since its inception PEIT and
      PEA have been regarded as an effective, inexpensive and low risk procedure.
      MATERIAL AND METHODS: We discuss mild and severe complications of these methods
      reported in literature and the first case so far of a severe ethyl toxic necrosis
      of the larynx and adjacent skin in a patient treated with PEIT by a radiologist.
      RESULTS: To date, no serious side effects have been reported in connection with
      these therapies. Some authors conclude that the side effects are in no way
      negligible and caution and routine should be exercised when using PEIT or PEA.
      Most complications have been transient in nature. The complication of ethyl toxic
      necrosis of the larynx was serious and the patient was admitted to hospital,
      treated conservatively and ten month later microsurgically. Voice thus could be
      restored to almost normal. CONCLUSIONS: PEIT for focal and diffuse autonomy, for
      cystic lesions of the thyroid, for thyroid hyperplasia and PEA for parathyroid
      hyperplasia are methods which are inexpensive and can be performed on an
      ambulatory base. These are the methods of choice if surgical intervention or
      radioiodine therapies are not practicable out of medical reasons or by refusal of
      the patient. The patient must be informed about possible severe complications.
      The examiner should have substantial experience in these methods. If
      complications an early opinion of a specialist is required.

PMID- 15852179
TI  - [Sonographic localisation procedures in hyperparathyroidism -- persistent
      hyperparathyroidism after removal of four parathyroid glands].
AB  - This case report will give an example for the necessity of performing an
      ultrasound examination of the neck before resection of the parathyroid glands. In
      end-stage renal failure a 38-year-old man developed secondary hyperparathyroidism
      (HPT). Four glands were removed. Two years later the patient revealed persisting
      HPT. At this point an ultrasound examination was performed and demonstrated a
      fifth parathyroid gland located inside the thyroid gland. The case illustrates
      the benefit of cervical ultrasound, even in cases of secondary
      hyperparathyroidism, prior to any cervical exploration.

PMID- 15852180
TI  - [Multiple bile duct hamartomas of the liver -- a rare differential diagnosis to
      liver metastasis].
AB  - Multiple bile duct hamartomas of the liver (von Meyenburg complex) are mostly
      incidental findings at autopsy. The 79-year-old female patient was presented to
      us with a superinfected Paget lesion of the right nipple. Ultrasound examination
      of the liver revealed multiple scattered hyperechoic lesions as well as some
      anechoic lesions, suspicious of metastatic disease. Computed tomography showed
      multiple focal lesions. The ultrasound-guided needle biopsy of the liver revealed
      multiple benign bile duct hamartamas. Magnetic resonance imaging ruled out
      diffuse malignant infiltration of the liver.

PMID- 15852181
TI  - [The case of a diagnostic puzzle -- aortic aneurysm or Ormond's disease? Ormond's
      disease or aortic aneurysm?].

PMID- 15852182
TI  - [Gleanings--(what does Asklepios mean? No mythology of ancient medicine].

PMID- 15852183
TI  - [The development of gallbladder sonography].

PMID- 15852191
TI  - [Diagnosis by hip sonography in an infant].

PMID- 15852197
TI  - Pathophysiology and treatment of menopausal hot flashes.
AB  - Hot flashes are the most common symptom of menopause. Although the appearance of
      hot flashes coincides with estrogen withdrawal, this does not entirely explain
      the phenomenon because estrogen levels do not differ between symptomatic and
      asymptomatic women. Luteinizing throughout? hormone pulses do not produce hot
      flashes nor do changes in endogenous opiates. Recent studies suggest that hot
      flashes are triggered by small elevations in core body temperature (T(c)) acting
      within a reduced thermoneutral zone in symptomatic postmenopausal women. This
      narrowing may be due to elevated central noradrenergic activation, a contention
      supported by observations that clonidine and some relaxation procedures
      ameliorate hot flashes. Because hot flashes are triggered by T(c) elevations,
      procedures to reduce T(c), such as lowering ambient temperature, are beneficial.
      Estrogen ameliorates hot flashes by increasing the T(c) sweating threshold,
      although the underlying mechanism is not known. Recent studies of hot flashes
      during sleep call into question their role in producing sleep disturbance.

PMID- 15852198
TI  - Vaginal hormone therapy for urogenital and menopausal symptoms.
AB  - Reduction of ovarian steroids at menopause leads to significant changes in the
      urogenital tract. These changes often worsen with time, particularly in
      nonsmokers, affecting up to 38% of menopausal women. Urogenital symptoms that
      clearly respond to estrogen therapy include atrophic vaginitis, dryness, and
      accompanying dyspareunia. Estrogen reduces urinary tract infections in women
      plagued by frequent recurrence. The sensation of urgency improves with estrogen
      but urge incontinence improvement is similar to that with placebo. Stress
      incontinence does not improve with estrogen. Until recently, vaginal therapy was
      reserved for local symptoms. Rings make systemic vaginal therapy acceptable and
      even preferred by some users. Vaginal delivery, like other parenteral therapies,
      bypasses the gastrointestinal tract, with less anticipated impact on lipids,
      globulins, clotting, and fibrinolytic factors. Evidence of a lowered risk of
      venous thromboembolism is reviewed. Options for estrogen therapy include native,
      synthetic, or biologically derived estrogens delivered by cream, gel, insert
      (pessary), ring, or tablet. Even the lowest dose estradiol (7.5 mug daily or 25
      mug twice per week) shows evidence of systemic absorption. In long-term placebo
      controlled studies, bone density was better preserved and lipid profiles were
      more favorable. Therefore, even these low dose therapies should be opposed by
      occasional progestogen to prevent endometrial carcinoma. Intermittent therapy is
      best given for a minimum of 12 days based on laboratory data. Less frequent
      dosing, although preferred by patients, likely confers a slightly increased risk
      of hyperplasia. No combination estrogen/progestogen vaginal product is currently
      available. The best dose to reduce risk of endometrial pathology adequately in
      the lower dose therapies will be defined not only by the dose and potency of the
      exogenous estrogen but by the individual is body habitus and lifestyle choices.

PMID- 15852199
TI  - Prevention of postmenopausal bone loss and treatment of osteoporosis.
AB  - Osteoporosis is now recognized as an increasingly prevalent disorder throughout
      the world. Fragility fractures and their subsequent short- and long-term
      complications are the adverse outcomes of this disease that is essentially silent
      until fractures occur. Given that the presence of one fragility fracture is an
      important predictor of the risk of subsequent fractures, prevention of the first
      fracture is critical whenever possible. Two key elements in fracture prevention
      that are discussed in this article are the attainment of optimal peak bone mass
      and the prevention of bone loss at menopause, with the major focus on the
      prevention of postmenopausal bone loss.

PMID- 15852200
TI  - The applicability of hormonal effects on atherosclerosis in animals to heart
      disease in postmenopausal women.
AB  - The discrepancy between estrogen's beneficial cardiovascular effects found in
      animal studies and observational studies in women compared with the recently
      published randomized clinical trials have stimulated a great deal of controversy.
      Possibilities for the discrepancy include the age of the women, number of years
      postmenopausal, and amount of atherosclerotic complication (necrosis and
      inflammation) present when hormone therapy is initiated. Many of the previous
      benefits of estrogens noted in both animal studies and observational studies were
      found in primary prevention studies that experimentally refer to a decrease in
      the progression of atherosclerosis extent rather than prevention of clinical
      events, which often occur in women with undiagnosed atherosclerotic plaques. In
      support of this notion, animal studies in which artery damage was present prior
      to hormone treatment, due to either consumption of an atherogenic diet or balloon
      injury of the endothelium, found no benefit with estrogen treatment. These animal
      studies are consistent with the lack of protection found in secondary prevention
      studies in women. Other areas of concern deal with the route of hormone delivery
      or dose of hormones used. Higher doses of oral estrogens may result in increased
      risk of inflammation and thrombosis. Future studies should be directed at
      studying hormone therapy in relevant ages of women (perimenopausal women) using
      the lowest effective doses of hormones and comparing oral and parenteral forms of
      delivery.

PMID- 15852201
TI  - Prevention of coronary heart disease: a nonhormonal approach.
AB  - Coronary heart disease (CHD) is a common and serious health problem facing women
      as they move beyond the reproductive years. Until recently, many postmenopausal
      women and their physicians relied heavily on hormone therapy to prevent
      cardiovascular disease, neglecting the well-recognized nonhormonal aspects of
      cardiovascular health. Simple lifestyle changes--exercise, diet, weight control,
      and avoidance of tobacco--can significantly reduce the chance of heart disease
      and its major risk factors, which are essentially the same for men and women. As
      with men, obesity, hypertension, hyperlipidemia, and diabetes are the major risk
      factors for heart disease in women. This review discusses the epidemiologic
      studies linking these risk factors to CHD in women, the guidelines for screening,
      and a brief overview of treatment recommendations.

PMID- 15852202
TI  - Breast cancer: the role of hormone therapy.
AB  - The possible association of estrogen (E) with or without progestin (P) and breast
      cancer has been addressed in many studies for several decades. The recent
      reported prospective double-blind Women's Health Initiative (WHI) study suggests
      that E + P increases the risk of breast cancer if a woman is an average of 63
      years old when she begins replacement therapy. One third of the patients in this
      study were 70 to 79 years of age when E + P was begun--obviously several decades
      past menopausal. Retrospective and observational studies suggest protection or no
      increased risk. The WHI-E only study actually notes a 23% reduction in breast
      cancer compared with the placebo. It would appear from a review of the literature
      that if there is an increased risk for breast cancer with E or E + P, it is
      minimal.

PMID- 15852203
TI  - Estrogen and cognition, with a focus on Alzheimer's disease.
AB  - Cognitive aging is associated with decreases in memory, attention, and
      visual/motor performance and skills. Dementia consists of loss of memory and
      other cognitive abilities, associated with social or occupational impairment.
      Potential neuroprotective effects of estrogen include lowering beta-amyloid,
      enhancing cholinergic function, promoting synaptic plasticity and nerve process
      growth, reducing oxidative stress, and enhancing brain glucose transport.
      Observational and longitudinal studies suggest that hormone therapy may attenuate
      age-associated cognitive impairment or decrease Alzheimer's disease but this has
      not been confirmed by randomized clinical trials. A critical window of time may
      exist around the menopause when hormone therapy may delay or decrease cognitive
      changes; however, hormone therapy initiated in the late postmenopause does not
      improve global cognition and may increase dementia risk.

PMID- 15852204
TI  - Female sexual dysfunction and use of hormone therapy in postmenopausal women.
AB  - Sexual dysfunction is a common problem for women of all ages and remains an
      important aspect of women's health following menopause. For postmenopausal women,
      the evaluation and management of sexual dysfunction differs from that of younger
      women because the etiology is often linked to the diminished levels of sex
      hormones. Female sexual function is highly complex and deeply influenced by
      nonhormonal factors such as emotional intimacy and culture. Our understanding of
      this important area of women's health remains inadequate, and much more research
      needs to be performed before definitive conclusions can be made. Existing data
      allow for some preliminary observations. It appears that lack of estrogen may
      lead to sexual dysfunction primarily by causing vaginal atrophy and dyspareunia.
      These symptoms may be treated by systemic or local estrogen therapy. Conversely,
      androgen deficiency appears to be most strongly linked to diminished sexual
      desire. Growing evidence indicates that administration of androgens may be
      beneficial in such situations. Other agents that use sex hormone receptors, such
      as selective estrogen receptor modulators and tibolone, also may affect sexual
      function.

PMID- 15852205
TI  - Lower doses of oral estrogen and progestogens as treatment for postmenopausal
      women.
AB  - Estrogen, with or without a progestin, is effective for the treatment of
      menopausal symptoms. Larger doses of estrogen/progestin have been used than
      required for the amelioration of menopausal symptoms. Both positive and negative
      outcomes of hormone therapy are reported in postmenopausal women. The positive
      aspects have been those associated with a reduction in menopausal symptoms such
      as hot flashes, and improvement in vulvovaginal atrophy with maintenance of bone
      mineral density. The problems have included an increased risk of venous
      thrombosis and breast cancer. The anticipation is that as the dose of oral
      estrogen and progestins is lowered, the benefits can be maintained and the side
      effects reduced. Recent clinical trials have found that lower doses of estrogen
      and/or progestin reduce or improve menopausal symptoms and maintain bone mineral
      density. The impact of lower doses of hormones on heart disease, and venous
      thromboembolism and stroke remain to be determined in future studies.

PMID- 15852206
TI  - [Psychiatrists - gatekeepers guarding welfare state benefits?].

PMID- 15852207
TI  - [Pro and contra: basic precedence of atypical neuroleptics].

PMID- 15852208
TI  - [Haematological abnormalities during treatment with atypical antipsychotics].
AB  - The danger of severe haematological abnormalities limits the use of clozapine in
      the treatment of psychoses. The development of modern second generation
      antipsychotics such as olanzapine, risperidone, quetiapine, amisulpride,
      ziprasidone or aripiprazol, however, makes it possible to use the positive
      effects of this class of drugs without the risks of a clozapine treatment.
      Nevertheless, there are several case reports about severe haematological
      abnormalities even during treatment with these second generation antipsychotics.
      This review summarises recently published cases and discusses the consequences
      for the daily clinical work.

PMID- 15852209
TI  - [Do psychiatric patients receive disability pension before adequate diagnostics
      and treatment? Evaluation of 101 psychiatric expertises done on behalf of Swiss
      Invalidity Insurance and the Psychiatric Outpatient Department Basel in 2002].
AB  - OBJECTIVE: a) Does the psychiatric expertise confirm the claimed psychiatric
      diagnoses in patients applying for a disability pension due to a psychiatric
      (co)morbidity? b) Had the patients received adequate psychiatric treatment before
      being sent for the psychiatric disability expertise? METHODS: Key data of 101
      psychiatric expertises done in 2002 on behalf of the Swiss invalidity
      insurance/Basel were analysed. RESULTS: a) 17% did not have a psychiatric
      diagnosis affecting the ability to work. In 50%, the ability to work was reduced
      by max. 30%, i. e. the prerequisites of a pension were not met. b) Patients with
      a psychiatric diagnosis affecting the ability to work: 50% reported to take a
      specific psychotropic medication, but only in 40% of them (i. e. 20% of the
      patients with a psychiatric disorder) the blood level was within the therapeutic
      range; only 35 % reported to have "some form of psychotherapy"; only 15% had been
      previously hospitalized. CONCLUSIONS: Many of the 101 patients applying for a
      disability pension had not been sufficiently diagnosed and had not received
      adequate psychiatric/psychotherapeutic treatment before the expertise.

PMID- 15852210
TI  - [The regional budget for mental health care: a new approach to combine inpatient
      and outpatient care].
AB  - OBJECTIVE: Due to increasing health care expenditures the discussion about
      advantages and disadvantages of new methods for resource allocation in mental
      health care has been intensified. A promising model is the Regional Budget for
      Mental Health Care, which is currently being examined in Schleswig-Holstein. The
      present paper describes first experiences with the new resource allocation model.
      BASIC CONDITIONS: An annual budget, provided for the treatment of a fixed number
      of patients, makes it possible to reduce inpatient capacity in favour of improved
      community-integrated approaches for the treatment of acute psychiatric illness.
      RESULTS: In a first step inpatient capacity will be reduced by 8 percent. By the
      end of 2007 capacity for hospital day care shall be increased by 87 percent and a
      home treatment will be implemented. The previous working method, orientated to
      treatment setting, will be replaced by an approach specialized in diagnostic
      groups. CONCLUSIONS: The Regional Budget could improve the continuity and
      flexibility of patient care. Service providers become motivated to treat in a
      way, which with little resource consumption achieves a long lasting health status
      improvement. For health insurances the Regional Budget is an opportunity to limit
      cost increases.

PMID- 15852211
TI  - [Age and gender: confounders for axis I disorders as risk factors for suicide].
AB  - OBJECTIVES AND METHODS: Aim of the study was to identify and estimate psychiatric
      axis I disorders as risk factors for suicide in different age groups using a
      psychological autopsy study with case-control design. 163 suicides and 396
      population-based control persons were assessed with a standardized semi
      structured interview including SCID-I (for DSM-IV). RESULTS: Logistic regression
      analyses revealed significantly elevated odds ratios for alcohol-related
      disorders in men aged 31 to 45, 46 to 60, and 61 to 75 years (OR = 9.0, OR = 7.5,
      and OR = 10.7, respectively) and for Major Depression, single episode, in men and
      women aged 61 to 75 years (OR = 42.7 and OR = 15.9). In males aged 31 to 45 years
      polysubstance-related disorders (OR = 9.5) and in females aged 61 to 75 years
      cognitive and mental disorders due to a general medical condition (OR = 12.2)
      were significantly and independently associated with suicide. CONCLUSIONS:
      Alcohol-related disorders and Major Depression differently contribute to male and
      female suicide risk in special age groups. These findings imply differentiated
      prevention strategies.

PMID- 15852212
TI  - [Employment of professional help by patients with obsessive-compulsive
      disorders].
AB  - BACKGROUND: Several studies have investigated the pathway to psychiatric care.
      There are no results available for OCD. METHODS: Therefore, 23 patients with OCD
      were recruited among individuals seeking treatment at our university hospital
      outpatient clinic for anxiety and obsessive-compulsive disorders. All patients
      underwent a semistructured interview aimed at investigating their individual
      pathways to psychiatric care, to their experiences in the health system and to
      the first appearances of the psychiatric disorder. RESULTS: Those affected often
      trivialize and normalize the first symptoms of OCD. Also, in many cases, family
      members of OCD-patients do not understand the first symptoms of OCD. Contrary to
      patients with depression and anxiety disorder, OCD-patients often choose
      psychiatrists as their first professional contact. DISCUSSION: The first symptoms
      of the disorder must be diagnosed at an early stage in order to provide the
      patients with the acknowledged therapy for OCD.

PMID- 15852213
TI  - [Rabbit syndrome due to olanzapine].
AB  - Rabbit syndrome (RS) is a rare extrapyramidal side effect of antipsychotic
      treatment. It is characterized by involuntary, rhythmic dyskinesias of mouth and
      lips excluding the tongue, and is most common under typical neuroleptics. There
      are also several reports of the syndrome in patients with the atypical
      antipsychotics risperidone and aripiprazole. We report a 74 year-old patient
      suffering from a bipolar affective disorder, who developed a rabbit syndrome
      following the intake of 20 mg/d olanzapine. To our knowledge this is the first
      case report of a RS due to olanzapine.

PMID- 15852216
TI  - Platelet aggregation and adenosine diphosphate/adenosine triphosphate receptors:
      a historical perspective.
AB  - The work of many investigators since adenosine diphosphate (ADP) was recognized
      as a platelet aggregating agent in 1961 has led to an appreciation of the
      important part that ADP plays in hemostasis and thrombosis. Recently, interest
      has focused on the platelet receptors for ADP and adenosine triphosphate (ATP).
      Platelets are unique because they have two P2Y receptors that must act in concert
      to achieve a normal aggregation response. The P2Y (1) receptor is responsible for
      mobilizing internal calcium, platelet shape change, and weak aggregation. The P2Y
      (12) receptor inhibits adenylyl cyclase, but the concentration of cyclic AMP is
      reduced only if it has been raised from its low basal levels by stimulation of
      adenylyl cyclase by an aggregation inhibitor such as adenosine or prostaglandin I
      (2). The abnormal bleeding of the rare patients whose platelets lack P2Y (12) and
      the beneficial clinical effects of ticlopidine and clopidogrel that block this
      receptor indicate that P2Y (12), in addition to inhibiting adenylyl cyclase, may
      have an as yet unidentified role that is needed for its cooperative aggregation
      effect with P2Y (1). ATP stimulates a rapid influx of calcium into platelets
      through the P2X (1) receptor, and it may synergize with ADP when these two
      nucleotides are released from platelets at a site of vessel injury.

PMID- 15852217
TI  - Overview of the P2 receptors.
AB  - The release of nucleotides in extracellular fluids can result from cell necrosis,
      exocytosis of secretory granules (such as platelet dense granules), or efflux
      through membrane channels. In addition, recent evidence suggests that vesicular
      trafficking is an important pathway of nucleotide release. Once in the
      extracellular fluids, they are rapidly degraded by ectonucleotidases, such as
      CD39, that play a key role in neutralizing the platelet aggregatory action of
      adenosine diphosphate (ADP), and act on two families of receptors: the ionotropic
      P2X receptors and the G-protein-coupled P2Y receptors. The family of P2X
      receptors encompasses seven genes. Currently, there are eight genuine P2Y
      receptors that can be subdivided into two structurally distinct subfamilies.
      Whereas P2X receptors are receptors of ATP, the different P2Y receptors are
      activated by distinct nucleotides, diphosphates or triphosphates, or purines or
      pyrimidines, some of them being conjugated to sugars. The study of knockout mice
      has demonstrated that P2X receptors play important roles in the neurogenic
      control of smooth muscle contraction, in pain and visceral perception, and in
      macrophage functions. The phenotype of P2Y null mice so far is more restricted:
      inhibition of platelet aggregation to ADP and increased bleeding time in P2Y (1)(
      /-) and P2Y (12)(-/-) mice and lack of epithelial responsiveness to nucleotides
      in airways (P2Y (2)(-/-)) and intestine (P2Y (4)(0/-)).

PMID- 15852218
TI  - The P2 receptors in platelet function.
AB  - After vessel wall injury, platelets adhere to the exposed subendothelium, are
      activated, and release mediators such as thromboxane A (2) (TXA (2)) and
      nucleotides stored at very high concentration in the so-called dense granules.
      Among other soluble agents, released nucleotides act in a positive feedback
      mechanism to cause further platelet activation and amplify platelet responses
      induced by agents such as thrombin or collagen. Adenine nucleotides act on
      platelets through three distinct P2 receptors: two are G protein-coupled
      adenosine diphosphate (ADP) receptors, namely the P2Y (1) and P2Y (12) receptor
      subtypes; the P2X (1) receptor ligand-gated cation channel is activated by
      adenosine triphosphate (ATP). The P2Y (1) receptor initiates platelet aggregation
      but is not sufficient for a full platelet aggregation in response to ADP, whereas
      the P2Y (12) receptor is responsible for completion of the aggregation to ADP.
      This receptor, the molecular target of the antithrombotic drug clopidogrel, is
      responsible for most of the potentiating effects of ADP when platelets are
      stimulated by agents such as thrombin, collagen, or immune complexes. The P2X (1)
      receptor is involved in platelet shape change and in activation by collagen under
      shear conditions. Each of these receptors is coupled to specific signal
      transduction pathways in response to ADP or ATP and is differentially involved in
      all of the sequential events involved in platelet function and hemostasis. As
      such, they represent potential targets for antithrombotic drugs.

PMID- 15852219
TI  - The platelet P2 receptors in thrombosis.
AB  - Adenosine diphosphate (ADP) and adenosine triphosphate (ATP) play a crucial role
      in hemostasis and thrombosis, and their receptors are potential targets for
      antithrombotic drugs. The ATP-gated channel P2X (1) and the two G protein-coupled
      P2Y (1) and P2Y (12) ADP receptors selectively contribute to platelet
      aggregation. Because of its central role in the formation and stabilization of a
      thrombus, the P2Y (12) receptor is a well-established target of antithrombotic
      drugs such as clopidogrel, which has proven efficacy in many clinical trials and
      experimental models of thrombosis. Competitive P2Y (12) antagonists have also
      been shown to be effective in experimental thrombosis as well as in several
      clinical trials. Studies in P2Y (1) and P2X (1) knockout mice and experimental
      thrombosis models using selective P2Y (1) and P2X (1) antagonists have shown
      that, depending on the conditions, these receptors could also be potential
      targets for new antithrombotic drugs. Because both P2X (1) and P2Y (1) receptor
      inhibition result in milder prolongation of the bleeding time as compared with
      P2Y (12) inhibition, the idea is put forward that combinations of P2 receptor
      antagonists could improve efficacy with diminished hemorrhagic risk. However,
      further studies with stronger and more selective P2 receptor antagonists are
      required to validate such a point of view.

PMID- 15852220
TI  - The P2 receptors and congenital platelet function defects.
AB  - Platelets possess three P2 receptors: two (P2Y (1) and P2Y (12)) are receptors
      for adenosine diphosphate (ADP), and one (P2X1) is a receptor for adenosine
      triphosphate (ATP). The P2Y (1) receptor, which is coupled to Gq and
      phospholipase C-beta, is responsible for mobilization of ionized calcium from
      internal stores and mediates the ADP-induced platelet shape change and initial
      wave of rapidly reversible aggregation. The other ADP receptor, P2Y (12), is
      negatively coupled to adenylyl cyclase through Gi and mediates a progressive and
      sustained ADP-induced aggregation not preceded by shape change. In addition, this
      receptor plays an important role in the potentiation of platelet secretion
      induced by several platelet agonists. The combined action of P2Y (1) and P2Y (12)
      is necessary for the full platelet aggregation response to ADP. Four patients
      with severe deficiency of P2Y (12) have been described so far. Sequence analysis
      of the P2Y (12) locus of three of these patients revealed homozygous mutations
      that produced a frame shift mutation and premature truncation of the protein. The
      fourth patient had an allele with a frame shift mutation and a normal allele,
      which could be silenced by an additional, as yet unknown, mutation. More
      recently, we described a patient with a congenital bleeding disorder and a
      dysfunctional P2Y (12). The patient is a compound heterozygote, in whom one
      allele contained a G to A transition resulting in an Arg (256) to Gln codon
      substitution (R256Q) and the other allele contained a C to T transition resulting
      in an Arg (265) to Trp codon substitution (R265W). The two substitutions are
      located in TM6 and EL3 of the receptor. Stable Chinese hamster ovaries (CHO) cell
      lines were established expressing either wild-type P2Y (12) and P2Y (12)(R256Q)
      or P2Y (12)(R265W). Neither mutation blocked the ability of the P2Y (12) receptor
      to translocate to the CHO cell surface. ADP at all tested concentrations (0.1 to
      10 muM) greatly inhibited the forskolin-induced increase of cyclic adenosine
      monophosphate (cAMP) in CHO cells transfected with wild-type P2Y (12), whereas
      CHO cells transfected with either mutant protein were only partially inhibited by
      ADP. Thus, the molecular basis for the patient's dysfunctional platelet phenotype
      is explained by missense mutations and the expression of a dysfunctional P2Y (12)
      receptor. The localization of both mutations in TM6 and EL3 identifies this
      region of P2Y (12) as a structurally and functionally critical region of the
      receptor.

PMID- 15852221
TI  - Clopidogrel and ticlopidine: P2Y12 adenosine diphosphate-receptor antagonists for
      the prevention of atherothrombosis.
AB  - Ticlopidine and clopidogrel belong to the same chemical family of thienopyridine
      adenosine diphosphate (ADP)-receptor antagonists. They have shown their efficacy
      as platelet antiaggregant and antithrombotic agents in many animal models, both
      ex vivo and in vivo. Although ticlopidine was discovered more than 30 years ago,
      it was only recently that the mechanism of action of ADP-receptor antagonists was
      characterized in detail. Ticlopidine and clopidogrel both behave in vivo as
      specific antagonists of P2Y (12), one of the ADP receptors on platelets.
      Metabolic steps that involve cytochrome P450-dependent pathways are required to
      generate the active metabolite responsible for this in vivo activity. The active
      moiety is a reactive thiol derivative that targets P2Y (12) on platelets. The
      interaction is irreversible, accounting for the observation that platelets are
      definitely antiaggregated, even if no active metabolite is detectable in plasma.
      The interaction is specific for P2Y (12); other purinoceptors such as P2Y (1) and
      P2Y (13) are spared. This results in inhibition of the binding of the P2Y (12)
      agonist 2-methylthio-ADP and the ADP-induced downregulation of adenylyl cyclase.
      Platelet aggregation is affected not only when triggered by ADP but also by
      aggregation inducers when used at concentrations requiring released ADP as an
      amplifier. The efficacy and safety of clopidogrel has been established in several
      large, randomized, controlled trials. The clopidogrel versus aspirin in patients
      at risk of ischaemic events (CAPRIE) trial demonstrated the superiority of
      clopidogrel over acetylsalicylic acid (ASA) in patients at risk of ischemic
      events, including ischemic stroke, myocardial infarction (MI), and peripheral
      arterial disease. The clopidogrel in unstable angina to prevent recurrent
      ischemic events (CURE) trial showed a sustained, incremental benefit when
      clopidogrel was added to standard therapy (including ASA) in patients with
      unstable angina and non-Q-wave MI. The clopidogrel for the reduction of events
      during observation (CREDO) trial demonstrated the benefit of continuing
      clopidogrel (plus ASA) for 12 months, as opposed to 1 month, after percutaneous
      coronary intervention. The proven efficacy of clopidogrel, coupled with its
      favorable safety and tolerability profile, has prompted its evaluation in an
      extensive, ongoing clinical trial program that will help to further characterize
      the benefit of clopidogrel in patients with a range of atherothrombotic profiles.

PMID- 15852222
TI  - Pharmacology of CS-747 (prasugrel, LY640315), a novel, potent antiplatelet agent
      with in vivo P2Y12 receptor antagonist activity.
AB  - CS-747 (prasugrel, LY640315) is a member of the thienopyridine class of oral
      platelet aggregation inhibitors that includes ticlopidine and clopidogrel. A
      single oral administration of CS-747 produced a dose-related inhibition of
      platelet aggregation in rats that was approximately 10- and 100-fold more potent
      than that of clopidogrel and ticlopidine, respectively. The antiaggregatory
      effect of CS-747 was evident at 30 minutes and lasted until 72 hours after
      dosing, indicating fast onset and long duration of action. CS-747 showed more
      potent antithrombotic activity compared with clopidogrel and ticlopidine with the
      same rank order as the antiaggregatory potencies. Combined administration of CS
      747 with aspirin to rats produced substantially greater inhibition of both
      platelet aggregation and thrombus formation compared with each agent alone. The
      antiplatelet action of CS-747 is due to irreversible and selective blockade of
      platelet P2Y (12) adenosine diphosphate (ADP) receptors by its active metabolite
      R-138727. In phase I studies, a single oral dose of CS-747 (30 and 75 mg)
      produced > 50% inhibition of ADP-induced platelet aggregation, with rapid onset
      (1 hour) and long duration (> 48 hours) of action. In healthy volunteers, once
      daily administration of 10 mg CS-747 for 10 days showed significant cumulative
      inhibition of platelet aggregation from 2 days after the first dose until at
      least 2 days after the final dose. Studies conducted to date indicate that CS-747
      is a highly effective antiplatelet and antithrombotic agent and is anticipated to
      be effective in the treatment of atherothrombotic and other ischemic vascular
      diseases.

PMID- 15852223
TI  - Preclinical and clinical studies with selective reversible direct P2Y12
      antagonists.
AB  - An important role for adenosine diphosphate (ADP)-induced platelet activation and
      aggregation was proposed more than 40 years ago. The clinical use of clopidogrel,
      a prodrug of an irreversible P2Y (12) antagonist, has further proved the
      relevance of inhibiting signaling via the platelet-specific P2Y (12) ADP receptor
      in the prevention of cardiovascular events. Pharmacological studies at
      AstraZeneca R&D Charnwood have identified direct, selective, and competitive P2Y
      (12) antagonists, including cangrelor (also known as AR-C69931MX), which is
      suitable for intravenous administration, and AZD6140, which is suitable for oral
      administration. In preclinical use, these compounds predictably and effectively
      inhibited platelet aggregation without significant increases in bleeding time. In
      clinical use, these compounds may have significant advantages over current
      antiplatelet agents. This article summarizes preclinical and clinical data on
      cangrelor and AZD6140 and discusses the potential of these compounds as novel
      antiplatelet therapies.

PMID- 15852224
TI  - Molecular recognition at adenine nucleotide (P2) receptors in platelets.
AB  - Transmembrane signaling through P2Y receptors for extracellular nucleotides
      controls a diverse array of cellular processes, including thrombosis. Selective
      agonists and antagonists of the two P2Y receptors present on the platelet surface
      the G (q)-coupled P2Y (1) subtype and the G (i)-coupled P2Y (12) subtype-are now
      known. High-affinity antagonists of each have been developed from nucleotide
      structures. The (N)-methanocarba bisphosphate derivatives MRS2279 and MRS2500 are
      potent and selective P2Y (1) receptor antagonists. The carbocyclic nucleoside
      AZD6140 is an uncharged, orally active P2Y (12) receptor antagonist of nM
      affinity. Another nucleotide receptor on the platelet surface, the P2X (1)
      receptor, the activation of which may also be proaggregatory, especially under
      conditions of high shear stress, has high-affinity ligands, although high
      selectivity has not yet been achieved. Although alpha,beta-methylene-adenosine
      triphosphate (ATP) is the classic agonist for the P2X (1) receptor, where it
      causes rapid desensitization, the agonist BzATP is among the most potent in
      activating this subtype. The aromatic sulfonates NF279 and NF449 are potent
      antagonists of the P2X (1) receptor. The structures of the two platelet P2Y
      receptors have been modeled, based on a rhodopsin template, to explain the basis
      for nucleotide recognition within the putative transmembrane binding sites. The
      P2Y (1) receptor model, especially, has been exploited in the design and
      optimization of antagonists targeted to interact selectively with that subtype.

PMID- 15852225
TI  - Ectonucleotidases of CD39 family modulate vascular inflammation and thrombosis in
      transplantation.
AB  - Transplantation results in exposure of the graft vasculature to warm and cold
      ischemia, followed by perfusion by circulating blood constituents and obligatory
      oxidant stress. Further graft injury occurs as consequences of acute humoral
      cellular rejection or chronic transplant vasculopathy, or both. Extracellular
      nucleotide stimulation of purinergic type 2 (P2) receptors are key components of
      platelet, endothelial cell (EC), and leukocyte activation resulting in vascular
      thrombosis and inflammation in vivo. CD39, the prototype nucleoside triphosphate
      diphosphohydrolase (NTPDase-1) is highly expressed on endothelium; in contrast,
      CD39L1/NTPDase-2 (a preferential adenosine triphosphatase [ATPase]) is found on
      vascular adventitial cells. Both ectoenzymes influence thrombogenesis by the
      regulated hydrolysis of extracellular nucleotides that differentially regulate P2
      receptor activity and function in platelets and vascular cells. The
      intracytoplasmic domains of NTPDase-1 may also independently influence cellular
      activation and proliferation. NTPDase activity is substantively lost in the
      vasculature of injured or rejected grafts. A role for NTPDase-1 in
      thromboregulation has been validated by generation of mutant mice either null for
      cd39 or overexpressing human CD39. Administration of soluble NTPDase or induction
      of CD39 by adenoviral vectors, or both, are also of benefit in several models of
      transplantation. Administration of soluble CD39 or targeted expression may have
      future therapeutic application in transplantation-associated and other vascular
      diseases.

PMID- 15852226
TI  - Role of CD39 (NTPDase-1) in thromboregulation, cerebroprotection, and
      cardioprotection.
AB  - Blood platelets maintain vascular integrity and promote primary and secondary
      hemostasis following interruption of vessel continuity. Biochemical or physical
      damage to coronary, carotid, or peripheral arteries promotes excessive platelet
      activation and recruitment culminating in vascular occlusion and tissue ischemia.
      Currently, inadequate therapeutic approaches to stroke and coronary artery
      disease (CAD) are a public health issue. Following our demonstration of
      neutrophil leukotriene production from arachidonate released from activated
      aspirin-treated platelets, we studied interactions among platelets and other
      blood cells. This led to concepts of transcellular metabolism and
      thromboregulation. Thrombosis has a proinflammatory component whereby
      biologically active substances are synthesized by different cell types that could
      not individually synthesize the metabolite(s). Endothelium controls platelet
      reactivity via at least three biochemical systems: autacoids leading to
      production of prostacyclin and nitric oxide (NO) and endothelial ecto-adenosine
      phosphatase (ADPase)/CD39/nucleoside triphosphate diphosphohydrolase (NTPDase-1).
      The autacoids are fluid phase reactants, not produced by tissues in the basal
      state, but are only synthesized intracellularly and released upon interactions of
      cells with an agonist. When released, they exert fleeting actions in the
      immediate milieu and are rapidly inactivated. CD39 is an integral component of
      the endothelial cell (EC) surface and is substrate activated. It maintains
      vascular fluidity in the complete absence of prostacyclin and NO, indicating that
      the latter are ancillary components of hemostasis. Therapeutic implications for
      the autacoids have not been compelling because of their transient and local
      action and limited potency. Conversely, CD39, acting solely on the platelet
      releasate, is efficacious in animal models. It metabolically neutralizes a
      prothrombotic releasate via deletion of ADP-the major recruiting agent
      responsible for formation of an occlusive thrombus. In addition, solCD39 reduced
      adenosine triphosphate (ATP)- and ischemia-induced norepinephrine release in the
      heart. This action can prevent fatal arrhythmia. Moreover, solCD39 ameliorated
      the sequelae of stroke in cd39 null mice. Thus, CD39 represents the next
      generation of cardioprotective and cerebroprotective molecules. This article
      focuses on our interpretations of recent data and their implications for
      therapeutics.

PMID- 15852228
TI  - On "Current role of antithrombotic agents in the treatment of acute coronary
      syndromes" (Semin Thromb Hemost 2004;30:627-632).

PMID- 15852229
TI  - [Reliability of fetal pulse oximetry for the detection of fetal acidosis].
AB  - Fetal pulse oximetry is a continuous method to exclude the lack of oxygen in
      cases of non-reassuring fetal heart rate. This study aims at the evaluation of
      the predictive value of this method concerning the development of fetal acidosis.
      136 fetuses with non-reassuring heart rate were monitored by fetal pulse
      oximetry. In all cases fetal blood pH and base excess were determined repeatedly
      by fetal blood analysis (FBA). The pH value and base excess in the umbilical
      artery and scalp blood as well as the changes of pH and base excess were
      correlated to the duration of low, medium and high fetal oxygen saturation (FSpO
      (2)). Sensitivity, specificity, positive and negative predictive values were
      calculated for the assumption that "FSpO (2) < or = 30 % for at least 10 or 15
      minutes" predicts a pH or base excess in the umbilical artery and in FBA of <
      7.1/7.15/7.2 or < or = -4/8/12 mmol/L and a decline of pH (base excess) by more
      than 0.05 (0.1) pH units (4 mmol/L). A highly significant negative correlation
      was found between umbilical artery and FBA pH and base excess as well as the
      change of both and the duration of low oxygen saturation. Additionally the change
      of FBA pH depends on the duration of medium FSpO (2). A pH below 7.15 in FBA as
      well as base excess < or = -12 mmol/L were safely detected by a cut-off of "FSpO
      (2) < or = 30 % for at least 10 minutes" and pH < 7.1 and base excess < or = -12
      mmol/l in FBA in 100 % and 75 %, respectively. A decline of pH by more than 0.1
      pH units and of base excess by more than 4 mmol/L were excluded by a negative
      predictive value of 98 %. In conclusion, medium and progressive acidosis can be
      reliably excluded by fetal pulse oximetry.

PMID- 15852230
TI  - [Mental disorders in the peripartum period--early detection and multi
      professional cooperation].
AB  - Given the great prevalence of mood disorders in early motherhood, the danger of
      chronic, particularly depressive mood disorders and the negative long-term
      effects on the socio-emotional development of the child requires specific and
      individual treatment. Midwives could serve as mediators between women patients
      and health care professionals. Therefore the project "Early detection and care of
      peripartum mood disorders, increasing options for reaching affected women" was
      initiated by the "German chapter of the International Marce Society" in
      cooperation with midwives. This paper presents results of the preliminary
      investigation. 111 midwives were interviewed in 12 centres in Germany,
      Switzerland and Austria regarding their experience and knowledge of psychic
      disturbances in early motherhood. Psychic disturbances are seen as an essential
      issue by the participating midwives. In their estimation 39 % of the pregnant
      women they cared for are exceptionally psychically burdened. In approximately 43
      % of the cases they believe that the physical complaints of pregnant women have a
      psychic background. In addition to "classic" mood complaints, midwives often
      perceive dysfunctions in the relationship between the mother and her child and
      that with her partner in the context of psychic disturbances during the
      peripartum period. In the diagnosis of psychic disturbances in early motherhood,
      attention should be paid to possible dysfunctional interactions between the
      mother and her child and that with her partner. Successful treatment of women
      with psychic disturbances in early motherhood requires cooperation between
      midwives, obstetricians and other health professionals.

PMID- 15852231
TI  - [Stimulation of HCG, estrogen and progesterone production in isolated trophoblast
      cells by glycodelin A or its N-glycans].
AB  - The immunosuppressive protein glycodelin A (GdA) is secreted by decidual tissue
      in high rates in the first trimester of pregnancy. GdA forms about 10 % of the
      total protein amount released by the decidua in the first trimester of pregnancy
      and has a unique glycosylation including fucosylated LacdiNAc structures. The
      purpose of this study was to investigate the effect of glycodelin A and its N
      glycans on hCG, estrogen and progesterone release by cytotrophoblasts in vitro.
      Trophoblast cells were isolated from human term placenta by fragmentation of
      villous tissue. Trophoblast cells fuse in vitro to syncytiotrophoblast cells.
      Trophoblast cells were incubated with GdA and various glycans of GdA. The
      production of hCG and progesterone was measured after 24 and 48 hours. The
      production of hCG, estrogen and progesterone was increased in GdA and glycan
      treated cell cultures as compared to untreated trophoblast cell cultures.
      CONCLUSION: HCG, estrogen and progesterone are markers for the differentiation
      process of cytotrophoblast cells. The results suggest that GdA with its distinct
      glycosylation modulates the differentiation of trophoblasts.

PMID- 15852232
TI  - Prenatal constriction of the fetal ductus arteriosus--related to maternal pain
      medication?
AB  - Physiological fetal circulation requires patency of the ductus arteriosus. As
      gestation proceeds, the sensitivity of the ductus to dilating prostaglandins
      diminishes. The sensitivity to constricting agents like PGE-synthetase
      inhibitors, present in many analgetics, however, increases. Fetuses affected by
      an antenatal constriction of the ductus arteriosus (DC) may present with
      different signs of cardiac failure including dilated right ventricle, tricuspid
      regurgitation and abnormal venous Doppler. We report on four cases with prenatal
      DC, presenting at 34, 35, 36 and 37 weeks of gestation. They were referred to
      fetal echocardiography because of abnormal routine echo scans with unexplained
      signs of right heart decompensation. Three patients were medicated during
      pregnancy with either aspirin (low dose), metamizole or ibuprofen. One patient
      did not take any drugs, especially no pain medication drug in pregnancy.
      Immediate delivery was performed in all cases. The neonates were in a good
      condition; echocardiography showed different degrees of right heart hypertrophy
      which disappeared in all infants by the age of 3 months except in case 2.
      Unexplained fetal right heart decompensation requires detailed echocardiographic
      evaluation of the ductus arteriosus and a sophisticated medical history with
      regard to analgesics. In contrast to ibuprofen and high-dose aspirin, metamizole
      and low-dose aspirin have not yet been reported as possible agents constricting
      the fetal arterial duct. In any suspected context, early delivery as in our cases
      may save babies life. Any application of non-steroidal anti-inflammatory drugs in
      pregnancy requires close fetal follow-up due to their potentially life
      threatening effect.

PMID- 15852233
TI  - [Comments on a report by the BQS on obstetric quality indicators].
AB  - When re-evaluating an epidemiologically oriented BQS expertise concerning the
      quality indicators in obstetrics, we examined three essential methods in
      obstetrics to verify their scientific evidence and their clinical relevance. In
      doing so we ascertained that recording the fetal heart rate sub part, analysing
      fetal blood and determining the blood gas of the umbilical blood are entirely
      appropriate quality indicators during delivery from a clinical and medical point
      of view -- although to varying extents. Above all, these three indicators prove
      to be essentially better evidence-based than described in the BQS expertise. The
      search for an optimum of evidence-based data in medicine ends in certain fields
      such as, for example, in obstetrics there where no further randomized studies can
      be carried out for methodological or ethical reasons. This lack of evidence for
      the optimum grade I which can clearly be understood from an epidemiological point
      of view, however, should not lead to an evidence nihilism that fails to accept or
      admit existing evidence of the weaker grades II and III.

PMID- 15852234
TI  - [Legal aspects of preparation and handling of concentrated red cells derived from
      placental blood in Germany].
AB  - Legal aspects of collection, preparation and storage of autologous red cells
      derived from cord blood according to German law are presented and discussed.

PMID- 15852236
TI  - Combining confocal and BSE SEM imaging for bone block surfaces.
AB  - The present report presents a method for the correlation of qualitative and
      quantitative BSE SEM imaging with confocal scanning light microscopy (CSLM)
      imaging modes applied to bone samples embedded in PMMA. The SEM has a proper
      digital scan generator: we leave the BSE image unchanged, and match the CSLM
      image to it, because the CSLM scan mechanism is not digital, though the signal is
      digitised. Our overlapping program uses a linear transformation matrix which
      projects one system to the other, calculated by finding three corresponding
      points in BSE and CSLM pictures. BSE images are empty where cells and osteoid are
      present. Fluorescence mode CSLM fills in these gaps. The combination images
      enhance our understanding of what is going on - and re-establish the need for
      good cellular preservation.

PMID- 15852235
TI  - Germline BHD-mutation spectrum and phenotype analysis of a large cohort of
      families with Birt-Hogg-Dube syndrome.
AB  - Birt-Hogg-Dube syndrome (BHD), a genodermatosis characterized by multiple
      hamartomas of the hair follicle (fibrofolliculoma), predisposes individuals to an
      increased risk of developing renal neoplasms and spontaneous pneumothorax.
      Previously, we localized the BHD locus (also known as FLCN) to chromosome 17p11.2
      by linkage analysis and subsequently identified germline mutations in a novel
      gene in probands from eight of the nine families with BHD in our screening panel.
      Affected members of five of the families inherited an insertion/deletion of a
      cytosine in a C8 tract in exon 11. This mutation was also identified by exon 11
      screening in probands from 22 of 52 additional families with BHD and therefore
      represents a hypermutable "hotspot" for mutation in BHD. Here, we screened the
      remaining 30 families from this large BHD cohort by direct sequence analysis and
      identified germline BHD mutations in 84% (51/61) of all families with BHD
      recruited to our study. Mutations were located along the entire length of the
      coding region, including 16 insertion/deletion, 3 nonsense, and 3 splice-site
      mutations. The majority of BHD mutations were predicted to truncate the BHD
      protein, folliculin. Among patients with a mutation in the exon 11 hotspot,
      significantly fewer renal tumors were observed in patients with the C-deletion
      than those with the C-insertion mutation. Coding-sequence mutations were not
      found, however, in probands from two large families with BHD whose affected
      members shared their family's BHD-affected haplotype. Of the 53 families with BHD
      whose members inherited either a germline mutation or the affected haplotype, 24
      (45%) had at least one member with renal neoplasms. Three families classified
      with familial renal oncocytoma were identified with BHD mutations, which
      represents the first disease gene associated with this rare form of renal
      neoplasm. This study expands the BHD-mutation spectrum and evaluates genotype
      phenotype correlations among families with BHD.

PMID- 15852237
TI  - Basic reactions of osteoblasts on structured material surfaces.
AB  - In order to assess how bone substitute materials determine bone formation in vivo
      it is useful to understand the mechanisms of the material surface/tissue
      interaction on a cellular level. Artificial materials are used in two
      applications, as biomaterials alone or as a scaffold for osteoblasts in a tissue
      engineering approach. Recently, many efforts have been undertaken to improve bone
      regeneration by the use of structured material surfaces. In vitro studies of bone
      cell responses to artificial materials are the basic tool to determine these
      interactions. Surface properties of materials surfaces as well as biophysical
      constraints at the biomaterial surface are of major importance since these
      features will direct the cell responses. Studies on osteoblastlike cell
      reactivity towards materials will have to focus on the different steps of protein
      and cell reactions towards defined surface properties. The introduction of new
      techniques allows nowadays the fabrication of materials with ordered surface
      structures. This paper gives a review of present knowledge on the various stages
      of osteoblast reactions on material surfaces, focused on basic cell events under
      in vitro conditions. Special emphasis is given to cellular reactions towards
      ordered nano-sized topographies.

PMID- 15852239
TI  - Physiology, pharmacology, and rationale for colloid administration for the
      maintenance of effective hemodynamic stability in critically ill patients.
AB  - The semisynthetic colloid solutions (gelatins, dextrans, and hydroxyethyl
      starches) are complex drugs. Their principal role in the care of the critically
      ill is as plasma volume expanders, but they may also affect hemorrheology,
      hemostasis, and inflammatory processes. The pattern of beneficial and detrimental
      effects varies between products. Understanding of the physiology of plasma volume
      expansion, as well as the nature and magnitude of these additional
      pharmacological qualities, is necessary for rational prescription of these
      commonly used products. The composition of the solute carrier solution can
      influence the clinical effects of colloid solutions. A large amount of data from
      laboratory and small clinical studies is available to inform this choice of
      colloid in a variety of situations. Significant patient outcome data from large
      studies has until recently been lacking, and clinicians have continued to
      prescribe a variety of crystalloids and colloids for the maintenance of effective
      hemodynamic stability in critically ill patients. The recently published Saline
      vs Albumin Fluid Evaluation Study demonstrates that albumin has an equivalent
      effectiveness and safety profile to 0.9% saline as a resuscitation fluid. The
      choice of clinical endpoints to guide dosage (infused volume) of colloids is
      probably therefore more important than the choice between individual products.

PMID- 15852241
TI  - Biopreservation of red blood cells: past, present, and future.
AB  - Preservation and long-term storage of red blood cells (RBCs) is needed to ensure
      a readily available, safe blood supply for transfusion medicine. Effective
      preservation procedures are required at various steps in the production of a RBC
      product including testing, inventory, quality control, and product distribution.
      Biopreservation is the process of maintaining the integrity and functionality of
      cells held outside the native environment for extended storage times. The
      biopreservation of RBCs for clinical use can be categorized based on the
      techniques used to achieve biologic stability and ensure a viable state after
      long-term storage. This paper will review the history, science, current
      practices, and emerging technologies of current RBC biopreservation approaches:
      hypothermic storage, cryopreservation, and lyophilization.

PMID- 15852240
TI  - Protecting the blood supply from emerging pathogens: the role of pathogen
      inactivation.
AB  - Although the risk of infection by blood transfusion is relatively low,
      breakthrough infections still occur, Transfusion-related fatalities caused by
      infections continue to be reported, and blood is not tested for many potentially
      dangerous pathogens. The current paradigm for increasing the safety of the blood
      supply is the development and implementation of laboratory screening methods and
      restrictive donor criteria. When considering the large number of known pathogens
      and the fact that pathogens continue to emerge, it is clear that the utility of
      new tests and donor restrictions will continue to be a challenge when considering
      the cost of developing and implementing new screening assays, the loss of
      potential donors, and the risk of testing errors. Despite improving the safety of
      blood components, testing remains a reactive approach to blood safety. The
      contaminating organisms must be identified before sensitive tests can be
      developed. In contrast, pathogen inactivation is a proactive strategy designed to
      inactivate a pathogen before it enters the blood supply. Almost all pathogen
      inactivation technologies target nucleic acids, allowing for the inactivation of
      a variety of nucleic acid-containing pathogens within plasma, platelets, or red
      blood cells thus providing the potential to reduce transfusion-transmitted
      diseases. However, widespread use of a pathogen inactivation technology can only
      be realized when proven safe and efficacious and not cost-prohibitive.

PMID- 15852242
TI  - Coagulation disorders and blood product use in patients undergoing
      thoracoabdominal aortic aneurysm repair.
AB  - Repair of thoracoabdominal aortic aneurysms (TAAA) is associated with major blood
      loss, often exceeding the patient's intravascular volume, and complex
      intraoperative and postoperative coagulopathies necessitating large-volume
      transfusion of blood products. Abnormalities sufficient to cause thrombocytopenia
      or clinically important prolongation of clotting parameters are rarely present
      before surgery in elective aneurysms but are more common with ruptured aneurysms.
      The finding of intraoperative and postoperative deficiencies of clotting factors,
      along with thrombin generation and activation of the thrombolytic system, is
      reflective of massive blood losses, visceral ischemia, and massive transfusions.
      An aggressive strategy of transfusion of blood products is critical to the
      prevention of clinically significant coagulopathy during surgery. Adjuncts to
      reduce blood losses and blood product use include low-dose aprotinin or epsilon 
      aminocaproic acid, intraoperative blood salvaging, and acute normovolemic
      hemodilution. In TAAA repair, an average blood loss of 5000 to 6000 mL and
      average transfusion of allogeneic blood products of 50 to 60 U are to be
      anticipated.

PMID- 15852243
TI  - The influence of various hematology analyzers on component platelet counts.
AB  - Hematology analyzers designed to count platelets in samples of whole blood are
      used to enumerate the total number of platelets in components prepared for
      transfusion. This report addresses the issue of variability in platelet counts
      obtained with different models of hematology analyzers. The influence of a common
      calibration procedure, involving one level of porcine platelets, on the extent of
      variability was also evaluated. Identical sets of samples of simulated and
      apheresis-derived human platelets were counted by multiple laboratories in 3
      separate studies. In the first 2 exercises, 7 samples of both porcine platelets
      and modified goat erythrocytes with targeted platelets counts from 0.2 to 4.0 x
      10(12)/L were counted without prior dilution. In both exercises, the samples were
      counted multiple times after routine calibration using instructions provided by
      the manufacturers of the various hematology analyzers used. In the second
      exercise, the samples were recounted after the hematology analyzers were
      recalibrated with a common calibrant consisting of porcine platelets at a
      targeted concentration of 0.5 x 10(12)/L. In the first and second exercises, 20
      and 18 hematology analyzers were used, respectively. In the third exercise, 6
      samples prepared from a single unit of apheresis platelets with targeted counts
      from 0.2 to 1.64 x 10(12)/L were shipped by an overnight courier and counted in
      triplicate on the day of arrival. Eleven hematology analyzers were used. The
      influence of recalibration was evaluated statistically by using the 95%
      prediction interval for the mean of a future set of observations. The platelet
      counts measured with a specific type of hematology analyzer provided the data to
      calculate the 95% prediction interval. With routine calibration, a wide
      variability in platelet counts was observed with all levels of both simulated and
      apheresis-derived human platelets. For example, with porcine platelets at a
      targeted level of 0.4 x 10 (12)/L, the platelet counts ranged from 0.31 to 0.47 x
      10(12)/L. Recalibration reduced the extent of variability observed with all
      levels of simulated and apheresis-derived human platelets by increasing the
      observed platelet counts determined with a subset of hematology analyzers that
      produced platelet counts in the lower portion of the range. With recalibration,
      the mean platelet counts obtained with most hematology analyzers, especially with
      samples having targeted platelet levels no greater than 1.0 x 10(12)/L, were
      within or near the 95% prediction interval determined with the instruments that
      provided the highest platelet counts with routine calibration. With
      recalibration, the reproducibility of the platelet counts was considered to be
      good for all hematology analyzers with all levels of simulated and apheresis
      derived human platelets for most of the instruments. The coefficient of variance
      did not exceed 6%, with most of the values ranging from 1% to 3%. This study
      therefore found that the platelet counts of platelet concentrates can be markedly
      influenced by the type of hematology analyzer used. A common calibration
      procedure designed specifically for the range of platelet counts in platelet
      products may be beneficial considering that many different hematology analyzers
      are being used to count platelets.

PMID- 15852244
TI  - Out of the box: an autobiography.

PMID- 15852246
TI  - Distinct mechanisms of action of tumor necrosis factor antagonists: what are the
      clinical implications?

PMID- 15852247
TI  - TNF pathophysiology in murine models of chronic inflammation and autoimmunity.
AB  - Experimental work in animal models is providing important clues on the specific
      function of tumor necrosis factor (TNF) and its receptors in disease, especially
      on the molecular and cellular pathways through which TNF mediates beneficial and
      deleterious responses. Emerging data on the posttranscriptional regulatory
      processes, secretion, and postreceptor actions of TNF indicate a variety of
      mechanisms that may be causative of disease. More recent evidence in murine
      disease models has indicated heterogeneity of TNF receptor usage in autoimmune
      disease suppression versus inflammatory tissue damage, suggesting that selective
      TNF receptor inhibition may be advantageous to anti-TNF treatments in combating
      chronic inflammatory disease.

PMID- 15852248
TI  - Differentiating the efficacy of the tumor necrosis factor inhibitors.
AB  - The tumor necrosis factor inhibitors are a diverse group of biologic agents.
      Although there are no studies that directly compare these agents, data from
      noncomparative trials suggest that all 3 agents have therapeutic activity in
      rheumatoid arthritis. Etanercept and infliximab have also demonstrated beneficial
      activity in other inflammatory arthritides (ie, psoriatic arthritis and
      ankylosing spondylitis [both agents] and juvenile rheumatoid arthritis
      [etanercept only]) and inflammatory diseases (ie, psoriasis and uveitis). Their
      effects in granulomatous diseases are more variable, with only infliximab
      demonstrating clear efficacy in the treatment of Crohn's disease, sarcoidosis,
      and Wegener's granulomatosis. The purpose of this brief review is to summarize
      current efficacy data and explore possible explanations for observed clinical
      differences.

PMID- 15852249
TI  - Clinical pharmacokinetics of TNF antagonists: how do they differ?
AB  - The relationship between the dose administered and the observed beneficial or
      adverse effects of a drug is one of the basic concepts of clinical pharmacology.
      The broad term "exposure" usually refers to the dose and the various acute or
      integrated measures of the resulting concentrations in blood (plasma, serum)
      and/or tissues/fluids. The term "response" refers to any direct measure of the
      pharmacologic effect (beneficial or otherwise) of the drug. Thus, as specified in
      a recent US Food and Drug Administration (FDA) Guidance for Industry (2004), "...
      a drug can be determined to be safe and effective only when the relationship of
      beneficial and adverse effect to a defined exposure is known." Consequently,
      there has been a recent strong academic, industrial, and regulatory interest in
      exploring and characterizing the exposure-response relationships of existing and
      developed drugs. The first part of the cascade exposure, response cascade, is the
      relationship between the administered dose and the observed concentration-time
      profiles in the organism of interest, often referred to as pharmacokinetics (PK).
      The second part is the relationship between the concentration levels and the
      observed pharmacodynamic (PD) responses, often called PK-PD relationship. Within
      the causal chain of events after a drug is administered, the exposure (or PK)
      precedes the effect (or PD). Therefore, whenever any differentiation in the
      beneficial and/or adverse effects between drugs with similar mechanisms of action
      is observed, the underlying clinical PK is among the first considerations. The
      purpose of the current article is to review the PK properties of the 3 existing
      marketed tumor necrosis factor (TNF) antagonists, adalimumab (Abbott
      Laboratories), etanercept (Amgen Inc.), and infliximab (Centocor, Inc.), and to
      discuss the potential clinical implications of any PK differences.

PMID- 15852250
TI  - Tumor necrosis factor inhibitors: clinical implications of their different
      immunogenicity profiles.
AB  - The beneficial effects of the anti-tumor necrosis factor (TNF) monoclonal
      antibodies infliximab and adalimumab and the soluble receptor fusion protein
      etanercept in the treatment of rheumatoid arthritis and a variety of other
      inflammatory disorders have been well described. However, less is known about the
      propensity of these agents to stimulate the production of antibodies against
      themselves and the clinical implications of such immunogenicity. A better
      understanding of the differential immunogenicity of these agents may help explain
      certain phenomena that have been reported with clinical use of anti-TNF agents
      (eg, infusion reactions [all agents], the need for increasing doses with
      prolonged use [infliximab]). This review will discuss our current understanding
      of the diverse immunogenic profiles of currently marketed anti-TNF agents.

PMID- 15852251
TI  - Diverse effects of infliximab and etanercept on T lymphocytes.
AB  - The tumor necrosis factor (TNF) antagonists infliximab and etanercept have proven
      to be useful additions to the armamentarium of agents used to manage patients
      with inflammatory disorders. However, as discussed in detail elsewhere in this
      supplement, these agents have different mechanisms of action and distinct safety
      and efficacy profiles in the clinical setting. Of particular interest are
      differing effects on T lymphocytes, thymocyte-derived cells that are responsible
      for cell-mediated immunity. Recent studies in 2 disease states, ankylosing
      spondylitis and Crohn's disease, have assessed the effects of TNF antagonists on
      T lymphocytes and reported differences that could partially explain some of the
      clinical disparities that have been reported.

PMID- 15852252
TI  - Epidemiology of lymphoma development in patients with rheumatoid arthritis.

PMID- 15852253
TI  - What are the links between Epstein-Barr virus, lymphoma, and tumor necrosis
      factor antagonism in rheumatoid arthritis?
AB  - EPSTEIN-BARR VIRUS (EBV) AND RHEUMATOID ARTHRITIS (RA): Patients with (RA) have
      slightly impaired EBV specific immunity. EBV AND LYMPHOMA: EBV contributes to the
      development of lymphoma, especially in immunosuppressed patients. LYMPHOMA IN RA:
      The incidence of lymphoma is increased (2-fold) in patients with active RA. TUMOR
      NECROSIS FACTOR (TNF) ANTAGONISM, LYMPHOMA, AND RA: The risk to develop lymphoma
      in patients with RA under TNF inhibitors is slightly higher than that of patients
      with active RA who do not receive TNF inhibitors. As already demonstrated in the
      case of posttransplantation lymphoma, EBV load monitoring in patients with RA
      under TNF inhibitors might allow predicting and preventing the emergence of
      lymphoma.

PMID- 15852254
TI  - Tumor necrosis factor and granuloma biology: explaining the differential
      infection risk of etanercept and infliximab.
AB  - Several studies show that the risk of granulomatous infections following therapy
      with the anti-tumor necrosis factor (TNF) antibody infliximab is higher than
      after treatment with the soluble TNFRp75 immunoglobulin fusion construct
      etanercept. Therefore, despite sharing a common target, it is possible that the
      actual mode of action of the 2 biologicals differs in vivo. TNF is known to
      participate in the induction and maintenance of protective granulomas at multiple
      steps, and evidence supporting a differential inhibition of TNF bioactivity and
      signaling by the 2 drugs is discussed.

PMID- 15852255
TI  - Mucoepidermal carcinoma of the lung detected by positron emission tomography in a
      5-year-old girl.
AB  - The authors describe a rare case of mucoepidermal carcinoma of the lung
      incidentally identified in preoperative assessments for inguinal hernia repair in
      a 5-year-old girl. This patient was referred for right external inguinal hernia,
      and a 3.0-cm round-shaped lesion was found in the right lower lung field of a
      chest x-ray film. She had no respiratory tract complaints, but her serum
      carcinoembryonic antigen concentration was markedly elevated (21.2 ng/mL). Chest
      and abdominal computed tomography/magnetic resonance images could not determine
      the nature of the lesion, but 2-[18 F]fluoro-2-deoxy- d -glucose positron
      emission tomography (FDG-PET) indicated a malignant tumor pattern. The patient
      underwent a computed tomography-guided needle biopsy of the lesion (S8), which
      was soon followed by a right lower pulmonary lobectomy. Histopathology of the
      resected specimen showed mucoepidermal carcinoma with no regional lymph node
      metastasis. In childhood asymptomatic pulmonary lesions, it is often difficult to
      rule out the possibility of malignancy. In the present case, FDG-PET scanning
      appropriately indicated the therapeutic priority of pediatric thoracic surgery.

PMID- 15852256
TI  - Respiratory insufficiency in a newborn with mesenchymal hamartoma of the chest
      wall occupying the thoracic cavity.
AB  - The authors describe a newborn patient with mesenchymal hamartoma of the chest
      wall associated with pulmonary hypoplasia. A massive thoracic tumor was diagnosed
      by prenatal ultrasonography and magnetic resonance imaging at the 28th week of
      gestation. She was delivered through cesarean delivery at the 36th gestational
      week. Respiratory distress because of pulmonary hypoplasia necessitated neonatal
      intensive care. The tumor extensively involved the left hemithorax including all
      12 ribs and the first 10 thoracic vertebrae, resulting in marked deformity of the
      thorax. At 5 days of age, she underwent the incisional biopsy through a left
      thoracotomy. Histopathology of biopsy specimens showed multiple components of
      mesenchymal origin including premature cartilage, bone, and cystic lesions
      resembling aneurysmal bone cyst. The tumor then showed a rapid overgrowth, but
      subsequently exhibited a self-limited growth for months, in which her respiratory
      condition gradually improved to spontaneous breathing without oxygenation
      support. The present case advocates perinatal preparations for associated
      pulmonary hypoplasia and conservative management for the neoplasm in fetuses
      prenatally diagnosed as having this unique pathological entity.

PMID- 15852257
TI  - Nodular lymphoid hyperplasia: a cause for obscure massive gastrointestinal
      bleeding.
AB  - Lower gastrointestinal bleeding in young adults is rare. Clinical diagnosis can
      be delayed because of obscured origin. Immediate and late patient clinical
      outcome is determined by the blood loss and risks of transfusion. The authors
      present a rare case of nodular lymphoid hyperplasia presenting as massive
      gastrointestinal bleed.

PMID- 15852258
TI  - Esophageal stenosis after coil embolization of an aortopulmonary collateral
      artery: report of a very unusual cause.
AB  - A 10-year-old boy who had previously undergone surgery for tetralogy of Fallot,
      pulmonary atresia, and ventricular septal defect was admitted with difficulty in
      swallowing and significant failure to thrive. His history included that he had 2
      angiographically detected aberrant pulmonary arteries extending from the
      descending aorta to the right and left lungs, respectively. Both collaterals had
      been ligated during the corrective surgery; however, early postoperative
      evaluation revealed that the vessel that crossed behind the esophagus to the left
      lung had become recanalized. Coil embolization was performed to occlude this
      collateral. The patient had begun to develop swallowing difficulties 2 years
      after the embolization. Esophagography revealed a significant stricture in the
      middle of the esophagus, just anterior to the location of the coil in the vessel
      behind. The patient underwent a program of esophageal dilatation. This was
      successful, and he regained normal swallowing ability. To our knowledge, no
      similar case of esophageal stenosis has been reported in the English literature.
      We believe that inflammation surrounding the coiled aberrant artery, presumably
      caused by injury during the corrective surgery and resulting in hemorrhage, led
      to fibrosis around the vessel. This fibrosis also involved the adjacent
      esophageal wall, thus causing progressive stenosis.

PMID- 15852259
TI  - Juvenile posttraumatic high-flow priapism: current management dilemmas.
AB  - High-flow priapism results from disruption of the intercavernosal artery
      resulting in an arteriocavernosal fistula and is rarely encountered in the
      pediatric and adolescent population. Clinically it manifests as a painless,
      prolonged erection after perineal trauma. Treatment has ranged from expectant
      management to open surgical exploration with vessel ligation. Internal pudendal
      arteriogram and superselective embolization with autologous blood clot has
      emerged as a safe and effective treatment modality in the young male population.
      Here the authors present 3 patients with high-flow priapism and discuss
      management of this rare clinical entity.

PMID- 15852260
TI  - Necrotizing fasciitis: a rare complication of hypospadias surgery in a child.
AB  - Necrotizing fasciitis is a rapidly progressive soft tissue infection involving
      the skin, subcutaneous tissue, and superficial fascia. It is a rare entity in the
      pediatric population. The specific etiologic factors that contribute to the
      establishment of necrotizing fasciitis in children are not evident. It may occur
      after minor trauma or operative procedures. The authors report a case of
      necrotizing fasciitis after hypospadias repair. This complication is extremely
      unusual and to the authors' knowledge has not been previously described.

PMID- 15852261
TI  - An unusual case of umbilical hernia rupture with evisceration.
AB  - Umbilical hernia is a common pediatric diagnosis for which the initial management
      is usually nonoperative. The high incidence of spontaneous closure and the
      infrequency of complications in the first few years of life justify this
      conservative management strategy. The authors present a case of a 5-month-old
      girl with a history of prematurity and prolonged ventilatory support, who
      subsequently experienced bowel evisceration via a previously uncomplicated
      umbilical hernia.

PMID- 15852262
TI  - Beware of the flaming hairball--a brief review and warning.
AB  - Operating room fires are receiving increasing attention in the medical literature
      and in the general public. The best way to reduce these iatrogenic, sometimes
      devastating, events is communication and education. The authors present the case
      of a 14-year-old adolescent girl who had an apparent explosive event during a
      laparotomy for removal of a large gastric trichobezoar. This event was presumably
      associated with gas production under increased pressures in the gastrointestinal
      tract caused by an obstructive and decomposing trichobezoar. This is the first
      reported association between trichobezoars and potential intraoperative fire
      and/or injury. It is the recommendation of the authors to avoid the use of
      electrocautery when initially entering a portion of the gastrointestinal tract
      thought to contain a bezoar to avoid the potential for surgical fire or
      concussive tissue damage.

PMID- 15852263
TI  - Successful bronchoscopic retrieval of Timothy grass from the airway.
AB  - Aspiration of Timothy grass in the airway is a well-recognized cause of
      bronchiectasis, and management often requires pulmonary resection. The authors
      describe 2 cases of Timothy grass aspiration with established pulmonary infection
      that were successfully managed by bronchoscopic removal with subsequent
      improvement. Every effort should be made to accomplish this goal, and pulmonary
      resection should be considered a last resort in these cases.

PMID- 15852264
TI  - Exhaust system burn injuries in children.
AB  - BACKGROUND/PURPOSE: The authors had noted a number of children who had sustained
      burn injuries from the exhaust systems of recreational vehicles and wished to
      document the incidence of pediatric burn injury sustained from the exhaust
      systems of a wide scope of motorized vehicles. METHODS: The authors conducted a
      10-year retrospective chart review including all children admitted to our
      institution with burn injuries from contact with vehicular exhaust systems.
      RESULTS: Twenty-three children were included. There were 18 boys, with a median
      patient age of 7 years. Most children (7 of 23) were injured from the exhaust
      systems of all-terrain vehicles. The average burn size (5%) was small, but almost
      two thirds of the burn injuries were full thickness. Of the 23 children, 21
      required operative intervention for their burns, with 2 children requiring
      multiple surgical interventions. The average length of hospital stay was 11 days,
      and all children, except one who went to a rehabilitation facility, were
      discharged to home. CONCLUSIONS: Pediatric health care providers should be aware
      that exhaust system contact burns in children are not rare events and they do
      tend to be significant. Surgical consultation should be requested early in the
      management of these particular burn injuries in children.

PMID- 15852265
TI  - Primary tracheal schwannoma (neurilemoma) in a 9-year-old girl.
AB  - The authors report a case of primary tracheal schwannoma (neurilemoma) causing
      symptoms of airway obstruction in a 9-year-old girl. Computerized tomography scan
      showed a polypoid intratracheal mass obstructing 73% of the lumen. Partial
      tracheal resection with primary anastomosis was performed. Histologic analysis
      showed a benign neurogenic tumor of Schwann cell origin.

PMID- 15852266
TI  - Postoperative paraplegia secondary to the use of oxidized cellulose (Surgicel).
AB  - Iatrogenic paraplegia after thoracic surgery is a devastating complication. In
      this report, the authors present a case of paraplegia in a toddler after the
      resection of a mediastinal neuroblastoma. In this case, the paraplegia was caused
      by spinal cord compression after migration of oxidized cellulose into the spinal
      canal.

PMID- 15852267
TI  - Managing bariatric patients in a children's hospital: radiologic considerations
      and limitations.
AB  - As the increasing prevalence of pediatric obesity and its associated risks gain
      national attention, adolescent bariatric surgery is gradually gaining acceptance
      as a viable weight loss tool for some severely obese adolescents. Obese patients
      often exceed the capacity limits of most radiological devices used for imaging.
      Because the radiological evaluation often plays a crucial role in the management
      of these patients, it is important for pediatric surgeons and radiologists to be
      aware of the special challenges and alternative algorithms for radiological
      evaluation. This review outlines and illustrates these considerations and
      limitations. Herein the authors discuss these topics within the context of
      characteristic bariatric patient profiles and the Roux-en-Y gastric bypass
      procedure, currently the authors' standard operative approach.

PMID- 15852268
TI  - Long-term results of 10 conjoined twin separations.
AB  - BACKGROUND/PURPOSE: From 1978 to 2000, 10 pairs of conjoined twins were
      successfully separated with 14 surviving twins. Six were separated emergently
      because of the death or impending death of their respective twins. All of the
      remaining 4 sets required at least one emergency operation on at least one twin
      before subsequent separations. METHODS: A 6-item questionnaire was developed to
      interview this unique cohort. The question design was open ended to maximize
      opportunity for patient/family response. Families were administered the same
      questionnaire in face-to-face interviews. The physician-author asked questions
      related to physical health and disability, whereas the social worker-author asked
      questions related to developmental, educational, psychosocial, and family
      functioning. RESULTS: The first 4 surviving twins have graduated from college.
      The 1981 twin completed high school. The remaining 9 twins are in classes
      appropriate for their age. All 14 twins have required operations subsequent to
      initial discharge, particularly to correct urological, orthopedic, neurosurgical,
      as well as pediatric surgical problems. CONCLUSIONS: In utero diagnosis of
      conjoined twins by ultrasonography compels physicians and parents early in the
      pregnancy to make decisions concerning possible surgical separation and the
      alternative of pregnancy termination. The case reports presented offer additional
      information for physicians and parents to make informed decisions at a crucial
      time by illustrating long-term physical and psychological outcomes of 14 surgical
      survivors.

PMID- 15852269
TI  - Rotavirus-induced murine biliary atresia is mediated by nuclear factor-kappaB.
AB  - BACKGROUND/PURPOSE: Intraperitoneal inoculation of rhesus rotavirus (RRV) was
      shown to cause atretic-appearing segments of the extrahepatic bile ducts (EHBDs)
      in a murine model. The factors responsible for the injury of bile ducts, however,
      remain unknown. In this study, the morphologic status of nuclear factor- kappa B
      (NF- kappa B) activation in the liver and in the EHBDs from murine model of
      biliary atresia induced by intraperitoneal injection of rotavirus was
      investigated. METHODS: Within the first 24 hours of life, the newborn mice were
      infected through intraperitoneal route with a volume of 50 microL containing
      different titers of RRV. The pups were killed on days 5, 10, 15, 21, and 28 after
      inoculation and prepared under a dissecting microscope with photographic
      documentation. Consecutive sections of specimens were stained with H & E and used
      for histopathologic studies. The methods of modified Vision immunohistochemical
      staining was used to detect viral antigen of VP7 and active NF- kappa B. The
      distribution and intensity of staining were analyzed by image analysis software
      (GT-2 model, Huakang Co, Chengdu, China). RESULTS: The viral antigen was detected
      by immunohistochemical staining in specimens from experimental groups on day 5
      after infection. The occlusion of the EHBDs could be visualized after
      intraperitoneal injection of 10(7) plaque-forming unit (pfu) of RRV, whereas the
      incidence of cholestasis was reduced with an infection dosage of 10(6) pfu or
      less. Obliteration of the EHBDs did not occur when the injection dosage of RRV
      was reduced to 10(5) pfu or when inoculation of 10(7) pfu of RRV was combined
      with pyrolidine dithiocarbamate (PDTC), a chemical inhibitor of active NF- kappa
      B. The antigen of active NF- kappa B was detected by immunohistochemical staining
      in the liver and in the EHBDs from pups after inoculation of 10(7), 10(6), and
      10(5) pfu RRV. Low or no expression of active NF- kappa B was noted in the
      specimens obtained from the control group. As the inflammatory reaction in the
      liver and in the EHBDs gradually subsided on day 28 after inoculation, the
      expression of active NF- kappa B also decreased. The expression of active NF-
      kappa B after injection of RRV combined with PDTC was similar to the expression
      in the control group on days 5 and 10 after infection. CONCLUSIONS: The authors
      found that occlusion of the EHBDs could be noted in pups after inoculation of
      10(7) pfu RRV. Meanwhile, the expression of active NF- kappa B in the liver and
      in the EHBDs was increased after inoculation of RRV. Simultaneous intraperitoneal
      injection of PDTC, however, was shown to prevent the obstruction of EHBDs
      secondary to inoculation of RRV. These results show that the murine biliary
      atresia induced by RRV is mediated by active NF- kappa B.

PMID- 15852270
TI  - Medial thickening of hepatic artery branches in biliary atresia. A morphometric
      study.
AB  - BACKGROUND/PURPOSE: Medial layer hypertrophy of hepatic arterial branches may be
      associated with biliary atresia (BA) pathogenesis. This study aimed at evaluating
      medial layer thickness in hepatic arterial branches at portoenterostomy and liver
      transplantation. METHODS: The authors evaluated 1274 arterial branches both in BA
      cases and in control subjects involving a total of 1108 arterioles and 166
      arteries. Arterial branch characteristics were morphometrically evaluated in 47
      BA patients at the time of portoenterostomy. Controls were patients with
      intrahepatic cholestasis (n = 3), immature neonates (n = 7), and infants (n = 7)
      without liver disease. Progression of medial layer thickening between the time of
      portoenterostomy and transplantation was evaluated in 7 BA patients. Biliary
      atresia patients at the time of transplantation were compared with non-BA
      transplanted patients (n = 4). RESULTS: The arterial medial layer of BA cases at
      portoenterostomy was thicker than that of infants without liver disease ( P =
      .03). The arterial medial thickness increased during the interval between
      portoenterostomy and transplantation ( P = .05). Arterioles and arteries with
      thickened medial layers were found in transplanted BA patients but not in
      patients transplanted for other liver diseases (P = .05 and P = .01). Thickening
      of the medial layer of the hepatic arteries was associated with focal
      distribution of interlobular bile ducts in portal spaces in BA ( P = .02).
      CONCLUSIONS: In BA, there is a progressive thickening of the arterial medial
      layer, suggestive of vascular remodeling, which is associated to the
      disappearance of interlobular bile ducts.

PMID- 15852271
TI  - Preoperative vascular imaging in pediatric liver transplantation.
AB  - BACKGROUND/PURPOSE: There is a considerable variation in the use of vascular
      imaging techniques in the preoperative assessment of children scheduled for liver
      transplantation. Duplex Doppler ultrasound scan (US), magnetic resonance
      angiography (MRA), and conventional angiography are used to varying extents. The
      authors compared the results of preoperative vascular imaging studies with
      operative findings to determine their accuracy and usefulness. METHODS: Results
      of preoperative vascular imaging in 37 consecutive children undergoing cadaveric
      liver transplantation were compared with operative findings. Those undergoing
      relatively elective transplantations were investigated by US and MRA (group 1),
      whereas those requiring urgent transplants were assessed only by US (group 2).
      RESULTS: The median age of the cohort (15 boys; 22 girls) was 4 years (19 days to
      16 years) and the median weight was 17 kg (2.9 to 82 kg). In group 1 (n = 26), 20
      children had a normal-caliber, patent portal vein at transplant and 6 had a
      narrow but patent portal vein requiring venous reconstruction in 4. The
      sensitivity and specificity of MRA in the detection of an abnormally narrow
      portal vein were 100% (6/6) and 95% (19/20), respectively. If reversed or absent
      flow in the portal vein on US was taken as an indication of a potentially
      abnormal vein, the sensitivity and specificity of Doppler US were 83% (5/6) and
      95% (19/20), respectively. Magnetic resonance angiography revealed arterial
      anomalies in 4 children but failed to detect small accessory hepatic arteries in
      5. The single patient with an aberrant vena cava was identified by MRA. In group
      2 (n = 11), venous findings at operation and on US were concordant in 10 (91%)
      cases; one infant with reversed flow in the portal vein on US had a thrombosed
      vein at surgery. Magnetic resonance angiography was useful in 2 patient groups:
      those with reversed flow on Doppler US or suspected portal vein thrombosis in
      whom an abnormal portal vein was present in 86% (6/7) and infants with the
      biliary atresia splenic malformation syndrome who had multiple venous and
      arterial anomalies. CONCLUSIONS: A detailed Doppler examination of the hepatic
      vasculature by an experienced sonographer/radiologist provides sufficient
      vascular imaging for most children scheduled for cadaveric liver transplantation.
      Routine MRA is recommended in children with the biliary atresia splenic
      malformation syndrome and in those with abnormal duplex Doppler US findings.
      Although there are limited data in this study, MRA is also valuable in children
      with Budd-Chiari syndrome, liver tumors, or a previous portosystemic shunt.

PMID- 15852272
TI  - S100A4 antisense oligodeoxynucleotide suppresses invasive potential of
      neuroblastoma cells.
AB  - BACKGROUND: S100A4 gene product has been implicated in tumor invasion and
      metastasis. The overall survival rate of children with neuroblastoma remains poor
      because of disease dissemination at the time of diagnosis. The purpose of this
      study was to investigate the effect and mechanism of S100A4 on invasion and
      metastasis of neuroblastoma. METHODS: A 20-mer phosphorothioate antisense
      oligodeoxynucleotide (asODN) targeted against the S100A4 mRNA was transfected
      into the human neuroblastoma cell line LA-N-6 by Lipofectamine 2000. The
      expressions of S100A4 and MMP-2 mRNAs were quantified by the reverse
      transcription polymerase chain reaction. The capability of migration and invasion
      of LA-N-6 cells were evaluated by the transwell chamber assay. RESULTS: The
      S100A4 mRNA and the MMP-2 mRNA levels in asODN-treated cells were decreased by
      35.6% and 25.5%, respectively, compared with those in nontreated cells. The
      numbers of migrating and invading LA-N-6 cells were both significantly lower in
      the asODN-treated groups than those in the nontreated groups ( 9.33 +/- 4.73 vs
      20.67 +/- 2.89 and 2.33 +/- 1.15 vs 9.00 +/- 2.65, respectively; both P = .03 ).
      CONCLUSIONS: The S100A4 asODN significantly reduced the S100A4 mRNA levels and
      the motility and invasive ability of neuroblastoma cells, with concomitant
      decrease of the MMP-2 mRNA levels. Thus, S100A4 may exert its effect on invasion
      and metastasis of neuroblastoma cells by stimulating the motility of tumor cells
      as well as influencing the expression of MMP-2.

PMID- 15852273
TI  - New trends in tumor biology: transfection of a human hepatoblastoma cell line
      with green fluorescent protein.
AB  - BACKGROUND/PURPOSE: Enhanced green fluorescent protein (eGFP) is widely used as a
      marker in different biologic systems. After vector transfection, eGFP is
      expressed by eukaryotic cells and can be visualized using fluorescent microscopy.
      The aim of this study was to establish an eGFP-transfected human hepatoblastoma
      (HB) cell line as tool for further basic research studies. METHODS: The HB cell
      line HUH6 was transfected with the pEGFP-N1 vector by liposomal transfection.
      Enhanced green fluorescent protein-positive cells were sorted out by fluorescence
      activated cell sort and selected using G418 resistance. Expression of eGFP
      messenger RNA was assessed by single-cell reverse transcriptase polymerase chain
      reaction after laser microdissection. Original and transfected cells were
      compared biologically and cytomorphologically. RESULTS: Vector transfection
      produced up to 15% eGFP-positive cells. After fluorescence-activated cell sort
      and G418 selection, a pure cell line was established with 100% eGFP-positive
      cells. Reverse transcriptase polymerase chain reaction revealed constant
      expression of eGFP-messenger RNA in fluorescending cells. Analysis of cell
      characteristics revealed no differences between transfected and original cells.
      CONCLUSIONS: For the first time, the authors established an eGFP-transfected HB
      cell line. This cell line can serve as a promising tool for further studies
      investigating HB in vitro and in vivo. Our model might also be a basis for
      similar work on other pediatric solid tumors.

PMID- 15852274
TI  - Antenatal vitamin A administration attenuates lung hypoplasia by interfering with
      early instead of late determinants of lung underdevelopment in congenital
      diaphragmatic hernia.
AB  - BACKGROUND/PURPOSE: Early and late lung underdevelopment in congenital
      diaphragmatic hernia (CDH) is likely caused by nonmechanical (directly mediated
      by nitrofen) and mechanical (mediated by thoracic herniation) factors,
      respectively. The authors investigated if vitamin A enhances lung growth because
      of effects on both early and late determinants of lung hypoplasia. METHODS:
      Twenty-seven pregnant Wistar rats were exposed on embryonic day (E)9.5 to 100 mg
      of nitrofen or just olive oil. From nitrofen-exposed pregnant rats, 12 were
      treated at day 9.5 or 18.5 with 15,000 IU of vitamin A. Lungs were harvested at
      E18, E20, and E22, weighed, and analyzed for DNA and protein contents. Left
      and/or right lung hypoplasia was estimated by assessment of the ratios of lung to
      body weight and left to right lung weight. Fetuses were assigned to 5
      experimental groups: baseline (exposed neither to nitrofen nor vitamin A),
      nitrofen (exposed to nitrofen without CDH), CDH (exposed to nitrofen with CDH),
      nitr+vitA (exposed to nitrofen without CDH and treated with vitamin A), and
      CDH+vitA (exposed to nitrofen with CDH and treated with vitamin A). RESULTS:
      Incidence of hernia was significantly reduced in fetuses treated with vitamin A.
      When vitamin A was administered at E9.5, the authors observed similar effect on
      lung hypoplasia measured through ratio of lung to body weight at E18 in the
      nitrofen and CDH groups (nitrofen 1.92% +/- 0.05%, CDH 1.92% +/- 0.04%), whereas
      lung hypoplasia was attenuated relative to baseline (2.45% +/- 0.05%) in 5% and
      4% in nitrofen (nitr+vitA 2.05% +/- 0.03%) and CDH (CDH+vitA 2.08% +/- 0.04%)
      groups, respectively. At E20, lung hypoplasia was increased in CDH compared with
      nitrofen groups (nitrofen 2.52% +/- 0.1%, CDH 2.39% +/- 0.05%), whereas vitamin A
      attenuated lung hypoplasia, in relation to baseline (3.20% +/- 0.07%), 14% in
      both nitrofen-exposed groups (nitr+vitA 2.96% +/- 0.03%, CDH+vitA 2.83% +/-
      0.03%). At E22, lung hypoplasia was significantly higher in CDH group than
      nitrofen group (nitrofen 2.13% +/- 0.06%, CDH 1.48% +/- 0.03%), whereas lung
      hypoplasia was attenuated in 9% of both nitrofen-exposed groups (nitr+vitA 2.35%
      +/- 0.06%, CDH+vitA 1.69% +/- 0.05%) in relation to baseline group (2.38% +/-
      0.04%). Administration of vitamin A at E18.5 produced no significant effects on
      lung growth. CONCLUSIONS: The authors conclude from these results that antenatal
      administration of vitamin A attenuates lung hypoplasia in CDH by interfering with
      early determinants of lung underdevelopment. This finding may have clinical
      implications because prenatal diagnosis of human CDH commonly occurs after 16
      weeks' gestation when late determinants of lung hypoplasia likely predominate.

PMID- 15852275
TI  - Reflux in esophageal atresia, tracheoesophageal cleft, and esophagocoloplasty:
      Bianchi's procedure as an alternative approach.
AB  - PURPOSE: Fundoplication has been used successfully to treat gastroesophageal
      reflux (GER) in the pediatric population. Although successful in many patients,
      there is a significant risk of complications and failure, especially in high-risk
      patients such as those with certain types of associated anomalies, diffuse
      motility disorders, chronic pulmonary disease, neurological impairment, and young
      infants. However, the results are poorer with children with severe pathologic
      lesion associated to reflux: tracheoesophageal cleft, esophagocoloplasty, and
      esophageal atresia (EA) with severe dysmotricity. In neurologically impaired
      children with neuromuscular incoordination and GER, Bianchi has proposed total
      esophagogastric dissociation (TED). The authors report the use of esophagogastric
      or esocologastric dissociation to control reflux in children with severe GER in
      other situations, such as EA, burn esophageal lesions having led to coloplasty
      and severe esotracheal cleft. METHODS: The authors reviewed the patients operated
      on for an esogastric or cologastric disconnection between 1997 and 2002. It is a
      single center retrospective study. The initial diagnosis, previous surgical
      procedure, postoperative course, and follow-up results were studied. RESULTS:
      Between September 1999 and June 2003, 13 TEDs were performed in 6 boys and 7
      girls. The mean age for TED procedure was 35 months (range 14 days to 218
      months). Indication for TED was severe persistent reflux in, respectively, 9
      cases of EA (7 with coloplasty and 2 with preservation of the native esophagus
      after atresia repair, associated in 1 case with an esotracheal cleft), 2 cases of
      esotracheal cleft type III, and 2 cases of esophagocoloplasty for caustic burns.
      Six patients had undergone previous fundoplications (1-4 procedures) that failed,
      whereas the remaining patients underwent TED as the primary antireflux procedure.
      The average follow-up was 26 months (range 1 month to 4 years). There were no
      complication during the immediate postoperative course. Three children died at 3,
      4, and 12 months after the procedure from acute respiratory failure. Respiratory
      status was improved in 8 children, and recurrent bronchitis was noted in 1 child.
      Regarding the digestive status, gastrostomy was closed at 18 and 24 months in 2
      children, and partial nocturnal enteral nutrition (200 to 900 mL/d) through the
      gastrostomy remains necessary in the other children. CONCLUSION: Total
      esophagogastric dissociation procedure improves the respiratory consequences of
      severe GER, particularly in children for whom other surgical treatments have
      failed. The long-term safety of this operation remains to be determined
      especially regarding the consequences of a gastrointestinal Roux-en-Y loop
      procedure.

PMID- 15852276
TI  - Should an infected Nuss bar be removed?
AB  - BACKGROUND: The Nuss procedure is a minimally invasive procedure for correction
      of pectus excavatum. It involves insertion of a substernal metal bar. A feared
      complication of any implanted device is infection, which often necessitates
      removal. The purpose of this report is to describe the authors' experience with
      infectious complications after the Nuss procedure. METHODS: From February 2000 to
      July 2002, 102 patients underwent the Nuss procedure in 2 pediatric surgical
      centers. In a retrospective way, the files of those patients in whom a
      postoperative infection developed were studied. RESULTS: Seven patients suffered
      postoperative infectious complications. Only one bar needed to be removed.
      CONCLUSION: The authors' experience indicates that there is no need for immediate
      removal of an infected Nuss bar. Most of these infections can be managed
      conservatively. However, early antibiotic treatment is warranted to ensure
      salvage of the bar.

PMID- 15852277
TI  - A new technique for removing the pectus bar used in the Nuss procedure.
AB  - BACKGROUND/PURPOSE: The Nuss procedure involves elevation of the sternum using a
      pectus bar, which is subsequently removed after approximately 3 years. When
      removing the bar, the tip of 1 end of the bar is exposed, and then the body is
      changed to the lateral recumbent position to remove the bar along the body
      surface. However, changing body positions in a sterile manner is often difficult.
      In this report, the authors present a new technique using their original bender
      design with which pectus bars can be smoothly removed. METHODS: After exposing
      the pectus bar by placing a skin incision in the same location as had been used
      for bar insertion, benders were inserted subcutaneously into the thoracic wall at
      both ends of the bar. The bar was then immobilized, straightened, and removed. No
      change of body position was required. CONCLUSIONS: Between 2002 and 2003, this
      technique was used on 10 patients, and the bars were removed easily from all
      patients. The new procedure uses benders at both ends of the pectus bar as
      supporting points. This reduces the force required to straighten the bar and
      stabilizes the bar during removal. Most importantly, our procedure eliminates the
      need for change of body position.

PMID- 15852278
TI  - Compartment syndrome in children and adolescents.
AB  - BACKGROUND: The authors performed a computerized search of the National Pediatric
      Trauma Registry for all patients who had compartment syndrome during a 51-month
      period. METHODS: One hundred thirty-three cases were identified. Boys outnumbered
      girls 4 to 1. The median age was 12 years and the peak incidence was in the 10-
      to 14-year-old age group. RESULTS: The most common mechanisms of injury were
      pedestrians struck by motor vehicles, falls, sports, and occupants in motor
      vehicle crashes. Eighty-five percent of the cases were the sequelae of fractures.
      Forearm fractures were the most common cause in the upper extremity, and tibia
      and/or fibula fractures were most common in the lower extremity. CONCLUSIONS:
      Open fractures significantly increased the risk of developing a compartment
      syndrome for both forearm and leg fractures. Sixty percent of the patients went
      directly from the emergency room to the operating room, suggesting that the
      others developed the compartment syndrome after admission, or had delayed
      diagnosis.

PMID- 15852279
TI  - Contractility of rat gubernacula affected by calcitonin gene-related peptide and
      beta-agonist.
AB  - PURPOSE: The effects of calcitonin gene-related peptide (CGRP), isoprenaline, and
      guanethidine on the neonatal rat gubernaculum were investigated in organ culture
      with the aim of seeing whether beta -agonists or beta -antagonists are involved
      in gubernacular development during testicular descent. METHODS: A total of 200
      gubernacula were studied. The gubernacula (n = 20 for each experiment) from male
      rat pups were incubated in aerated culture medium with isoprenaline (1 and 10
      micromol/L) with/without CGRP (714 nmol/L) or guanethidine (1 and 10 micromol/L)
      with/without CGRP (714 nmol/L). Cultures were observed for 5 days by video camera
      to see spontaneous rhythmic contractions, which are known to correlate with
      normal gubernacular migration in the rodent. RESULTS: Of gubernacula cultured
      without CGRP, 60% showed contractions by day 5, and the groups of isoprenaline
      and 10 micromol/L guanethidine showed similar rates, but only 15% of the 1
      micromol/L guanethidine group showed contractility (P < .005). In contrast, of
      the gubernacula cultured with CGRP, each group showed high contractility from day
      2 of the culture, and there was no difference between each group and the CGRP
      alone group. CONCLUSIONS: Although the beta -blocker showed a weak inhibitory
      effect on de novo gubernacular contractility, CGRP had a stronger effect on
      contractility, overriding any possible effects of the beta -neuron pathway. The
      contractility of the rat gubernaculum during testicular descent is primarily
      mediated by the genitofemoral sensory nerve fibers via release of CGRP, but beta 
      adrenergic nerves also may be involved.

PMID- 15852280
TI  - Influence of the type of operations on the development of latex sensitization in
      children with myelomeningocele.
AB  - BACKGROUND: A genetic tendency to develop latex IgE responses in children with
      spina bifida has been suggested, but their degree of exposure to latex as well as
      the route and chronology for sensitization can be different from those of other
      children with multiple surgeries. The aim was to study the influence of the type
      of operation on the development of latex sensitization in children with
      myelomeningocele. METHODS: In 90 children with myelomeningocele operated with
      latex, data were collected about age, sex, family, and personal history of
      allergy, serum total IgE, presence of a ventricular-peritoneal (v-p) shunt, and
      number and duration of operations, classified as urological, orthopedic, on the v
      p shunt, other neurosurgical, and others. A multivariate logistic regression
      analysis was performed, using the presence of latex sensitization as dependent
      variable. RESULTS: Serum total IgE, the number of urological and of orthopedic
      operations were synergistic variables to predict latex sensitization, together
      with the presence of a v-p shunt, but not the number of operations performed on
      this device. This seems to play an adjuvant role in the process of sensitization.
      CONCLUSIONS: Not only the number, but also the type of operations, namely, of
      urological and orthopedic nature, is important in the development of latex
      sensitization in children with myelomeningocele.

PMID- 15852281
TI  - Ligamentum paracolicum dextrum--a new ligament?
AB  - PURPOSE: During routine laparoscopy, the authors identified an unknown ligament
      that stretched between the middle segment of the ascending colon and the adjacent
      lateral abdominal wall. This report discusses the incidence and histology and
      suggested name for this ligament. METHODS: Over a 5-year period, 362 hernias were
      repaired laparoscopically in children aged from 4 days to 14 years (median 1.7
      years; 87 girls and 242 boys). None of the children had undergone previous
      surgery nor had had concomitant diseases or associated malformations. The
      ligament was searched for in every child. In addition, 22 adult cadavers were
      dissected searching for the ligament. Biopsies were taken from the ligament and
      from adjacent abdominal wall in other cadavers as controls. RESULTS: During
      laparoscopy, a ligament of variable size was identified in 152 of the children
      (43%). This ligament arose at the lateral aspect of the middle ascending colon,
      occupied half of the circumference, and inserted at the lateral abdominal wall;
      there was no recognizable relation to any defined structure at the abdominal wall
      itself. Similar ligaments were also identified during the cadaveric dissections
      in 14 (64%) of 22 adult cadavers, in which the variable thickness and broadness
      were also noted. Histological examination of samples taken from the cadavers
      showed a loosely structured subepithelial layer of connective tissue of variable
      width, which transitioned gradually into the subperitoneal fat tissue.
      CONCLUSIONS: This ligament easily evades the attention of surgeons in open
      surgery, yet becomes evident during laparoscopy. In the semilateral or lateral
      position, most frequently chosen for transabdominal laparoscopic access to the
      kidney, the ligament stretches and keeps the colon on top of the kidney. The
      ligament's clinical and anatomic significance is unknown. Its existence has
      become more evident with recent use of laparoscopy.

PMID- 15852282
TI  - Laparoscopic management of nonpalpable testes: a multicenter study of the Italian
      Society of Video Surgery in Infancy.
AB  - PURPOSE: Diagnostic laparoscopy has changed the surgical approach to nonpalpable
      testes (NPT). The aim of this study was to determine the value of laparoscopy in
      managing patients with NPT and to suggest guidelines for the interpretation of
      laparoscopic findings. The authors report the results of a multicenter study of
      the Italian Society of Video Surgery in Infancy on laparoscopic management of
      NPT. METHODS: Between 1993 and 2001, the authors collected records of 364
      patients with NPT who underwent laparoscopy, for a total of 388 testicular units.
      RESULTS: Intraabdominal testes were found in 124 (34%) cases, for a total of 137
      testes; 83 testicular units were classified as low and 54 as high. A total of 155
      (43%) patients had cord structures entering the internal inguinal ring, 79 (22%)
      had intraabdominal blind-ending cord structures, and 6 (1%) had testicular
      agenesia. CONCLUSIONS: Laparoscopy is a valuable tool in diagnosing and treating
      more than 50% of cases of NPT. The laparoscopic evaluation of abdominal testes
      can provide indications for the most suitable surgical technique; moreover, in
      23% of patients, it makes abdominal exploration unnecessary. The value of
      laparoscopy is even greater if the anatomical aspect of the internal ring and
      spermatic cord structures is carefully evaluated.

PMID- 15852283
TI  - Surgical management of primary bladder diverticula in children.
AB  - PURPOSE: The aim of this study was to review the authors' surgical experience
      with primary bladder diverticula in the pediatric population, with special
      attention to associated urinary tract infections and voiding dysfunction.
      METHODS: A retrospective review yielded 21 pediatric patients with primary
      bladder diverticula treated surgically over a 13-year span. Patients with
      secondary diverticula were excluded. Charts were reviewed and patients were
      contacted in regards to several factors. Diverticula were diagnosed
      preoperatively by radiography on a voiding cystourethrogram. Diverticula, which
      were only found intraoperatively and not on VCUG, were not included in the study.
      RESULTS: Mean age at presentation was 8.16 years (range of 0.17-12.91 years). The
      sex predominance was male, 17 (81%) of 21. Mean follow-up was 44.2 months (range
      of 6-156 months). The diverticula were associated with ureters requiring
      reimplantation in 15 of 21 patients (72.4%); only 6 (28.6%) of 21 were isolated
      diverticula. Nineteen (90.5%) of 21 patients presented with infections, and all
      19 (100%) have had complete resolution of infections. Of the total, a subset of 6
      patients with isolated diverticula and no evidence of reflux had total resolution
      of their infections. Twelve patients presented with voiding dysfunction. Eight of
      these 12 patients had improvement of their voiding dysfunction with complete
      resolution in 2 patients. CONCLUSIONS: In this series, infections were eliminated
      with surgical excision of the primary diverticula. Surgical repair was also
      associated with improvement of voiding dysfunction.

PMID- 15852284
TI  - Long-term results of conservative management of adnexal torsion in children.
AB  - BACKGROUND/PURPOSE: Adnexal torsion is a condition that may result in serious
      morbidity including adnexal removal. However, conservative management with
      preserving the torsed adnexa is not justified, and long-term outcomes remain
      unclear. METHODS: The records of 14 girls with ovarian torsion whose adnexal
      structures were preserved after detorsion were reviewed to evaluate the long-term
      results of conservative management. Data including age, previous history,
      duration of complaints, surgical findings and type of intervention, color Doppler
      ultrasound findings performed in the early and late postoperative periods, and
      final outcomes were collected. RESULTS: Mean age of patients was 11.5 +/- 2.8
      (range 6 to 15) years. Time interval between the onset of pain to surgery was
      46.78 +/- 35.5 (range 12 to 126) hours. Seven patients had a benign solitary cyst
      as an underlying cause for adnexal torsion. The intervention performed by open
      surgery in 9 and by laparoscopy in 5 patients included detorsion, simple cyst
      aspiration, unroofing and/or cystectomy in 7 patients with ovarian cysts, and
      oophoropexy in 9 of 14 patients. Follow-up ranged from 3 to 66 (mean 21.9 +/-
      20.1) months. Thirteen patients resumed normal size and folliculogenesis, whereas
      in 1 patient, the involved ovary atrophied. No recurrence or contralateral
      adnexal torsion was observed on follow-up. CONCLUSIONS: Conservative management
      with untwisting the ovary and pexing both retained detorsed and contralateral
      ovaries especially in idiopathic torsions should be considered in cases of
      ovarian torsion in children.

PMID- 15852285
TI  - The response of clinical balanitis xerotica obliterans to the application of
      topical steroid-based creams.
AB  - OBJECTIVE: The aim of this study was to assess the effectiveness of using topical
      steroid-based creams in the management of clinically diagnosed balanitis xerotica
      obliterans (BXO) in boys. METHODS: The response in 56 boys to locally applied
      steroid-based creams was studied retrospectively. All had been referred by their
      general practitioners with symptoms of penile pathology and then subsequently had
      a clinical diagnosis of BXO made. The boys were initially assessed after 3 months
      of treatment and then at various intervals depending on their response. RESULTS:
      The mean age at presentation of the boys was 8.9 (4 to 15) years. After the
      initial 3-month assessment, 10 (17.9%) boys had complete resolution. When the
      treatment period was prolonged by an average of 14 months, the total number of
      boys showing resolution increased to 17 (30.4%). All boys showing resolution had
      clinically mild BXO limited to the prepuce only. Those patients with established
      scar formation on the foreskin showed no significant improvement. CONCLUSIONS:
      Topical steroids seem to offer a reliable option only in the management of mild
      BXO limited to the prepuce in boys with minimal scar formation. Steroid-based
      creams can be offered to such patients provided they and their families are
      realistic as to the likelihood of success. This treatment is ineffective in the
      face of established scarring.

PMID- 15852286
TI  - Phimosis. Preputial plasty using transversal widening on the dorsal side with
      EMLA local anesthetic cream.
AB  - BACKGROUND/PURPOSE: In the United States, the treatment of choice for the
      correction of phimosis is circumcision, whereas in European countries, the
      condition is usually treated by preputial plasty using Duhamel's method or
      modified versions. We report our experience in correcting phimosis by preputial
      plasty using transversal widening on the dorsal side with EMLA local anesthetic
      cream. METHODS: Twenty-six patients with phimosis were operated on by preputial
      plasty, under local anesthesia with EMLA cream. A transversal incision is made on
      the dorsal side of the ring of prepuce, like 3 contiguous Ts, the middle one
      inverted with the long arm on the preputial mucosa side. The 2 small
      mucocutaneous flaps of the prepuce are separated and then sutured with
      interrupted stitches, thus transforming the incisions from T to V. RESULTS: No
      postoperative complications were observed. At 1-year follow-up, the cosmetic and
      functional results were satisfactory. CONCLUSIONS: The technique of preputial
      plasty that the authors present enlarges the stenotic ring of prepuce by a
      transversal widening on the dorsal side. The ring of prepuce obtained is wide and
      symmetrical on its dorsal and ventral sides and therefore cosmetically and
      functionally satisfactory. It is a good alternative to the more radical
      circumcision technique.

PMID- 15852287
TI  - A peculiar multiple polypoid mucosal prolapse causing jejunal intussusception.
AB  - A case of jejunal intussusception caused by a multiple polypoid mucosal prolapse
      of jejunum in a 10-year-old girl is reported. The rarity of the lesion, its
      location, symptoms, and diagnosis are discussed.

PMID- 15852288
TI  - Are patients who have had a tracheoesophageal fistula repair during infancy at
      risk for esophageal adenocarcinoma during adulthood?
AB  - The authors present a case of a 46-year-old woman who had esophageal
      adenocarcinoma after having had a tracheoesophageal fistula (TEF) repair as an
      infant. A Medline search, which identified 2 other patients in the world
      literature who developed esophageal cancer (squamous cell carcinoma [J Pediatr
      Surg 36(4) (2001) 629-630] and adenocarcinoma [J Pediatr Surg 24(8) (1989) 741
      744]) after TEF repair, was performed. As such patients reach middle age, it is
      possible that they are at increased risk for the development of esophageal
      cancer. Practitioners should be aware of the possibility of increased risk in
      this population and perhaps the need for a study to screen patients who have had
      a TEF repair to assess the incidence of cancer.

PMID- 15852289
TI  - Premature closure of the upper esophageal sphincter as a cause of severe
      deglutition disorder in infancy.
AB  - Deglutition disorders in infancy are often associated with birth asphyxia or
      structural abnormalities in the hypopharynx, the trachea, or the esophagus.
      Manometry can be crucial for clarifying the dynamics of the swallowing disorder
      in the infant with deglutition problems and without signs of these causes. An 8
      week-old infant was referred because of suspicion of cricopharyngeal achalasia
      causing persistent swallowing problems and failure to thrive. Manometry results
      showed normal resting tone and relaxation but premature closure of the upper
      esophageal sphincter. The infant was treated with balloon dilatation of the upper
      esophageal sphincter and expectance. A maturation process of the swallowing
      sequence was noted over time and documented by repeated manometric procedures.

PMID- 15852290
TI  - Fraternal twins with Morgagni hernias.
AB  - Fraternal twins with identical left-sided foramen of Morgagni hernias are
      described. The occurrence of this rare type of congenital diaphragmatic hernia in
      twins suggests that genetic factors play a role in the formation of this lesion.

PMID- 15852291
TI  - Laparoscopic resection of congenital choledochal cyst, hepaticojejunostomy, and
      externally made Roux-en-Y anastomosis.
AB  - The authors present a 3-month-old patient with a congenital choledochal cyst,
      which was asymptomatic until treatment. On laparoscopy, a type I choledochal cyst
      was confirmed and excised laparoscopically. A Roux-en-Y anastomosis was
      constructed after exteriorization of the small bowel via the infraumbilical
      trocar incision. A laparoscopic end-to-side hepaticojejunostomy was carried out.
      The operation lasted 4(1/2) hours, without intraoperative problems. Oral food
      intake was started on day 2 and well tolerated with bile stained stools. Symptoms
      of bowel obstruction occurred on day 8. On minilaparotomy, the Roux-en-Y
      anastomosis was found to be adherent to the mesenterium of the colon, leading to
      obstruction. After mobilizing the loop, the postoperative course was uneventful.
      We conclude that laparoscopic resection of congenital choledochal cyst and
      choledochojejunostomy was feasible in the youngest patient operated on so far.
      However, adhesive small bowel obstruction can also occur, as after conventional
      operation, when the bowel is exteriorized for Roux-en-Y hepaticojejunostomy.

PMID- 15852292
TI  - Hemorrhagic abdominoscrotal hydrocele. A challenging entity.
AB  - Abdominoscrotal hydrocele (ASH) is a rare condition in childhood. It presents an
      intraabdominal portion with homogeneous content that is usually excised through a
      groin approach. A pale child with a recurrent scrotal hydrocele and a huge solid
      cystic retroperitoneal mass is reported. Because the diagnostic workup has not
      ruled out malignancy, a laparotomy was performed; however, ultimate diagnosis was
      hemorrhagic ASH. The clinical features and surgical management of ASH are
      addressed. This entity should be considered in front of tense or recurrent
      hydroceles or coexistent abdominal mass even though with heterogeneous content.

PMID- 15852293
TI  - Giant omental lipoma in children.
AB  - Lipoma is a rare benign neoplasm of mature fat cells. Asymptomatic abdominal
      mass, progressive abdominal distension, and intraperitoneal radiolucent fat
      density mass on computed tomography are the main clinical symptoms and signs. An
      unusual case is presented in this report. A complete excision was performed on an
      11-month-old boy with a giant omental lipoma, and no recurrence was found in the
      12-month follow-up.

PMID- 15852294
TI  - Pseudo-Meigs syndrome secondary to ovarian germ cell tumor.
AB  - An 11-year-old white girl presenting with fever, dyspnea, and cough demonstrated
      a left pleural effusion, ascites, and a suprapubic mass on physical and
      radiologic examinations. Surgical resection of the mass found a stage Ic
      malignant mixed germ cell tumor of the ovary. The pleural effusion and ascites
      were benign and resolved spontaneously after complete resection of the tumor,
      which is characteristic of a pseudo-Meigs syndrome.

PMID- 15852295
TI  - Family cases of gastroschisis.
AB  - The etiology of gastroschisis is still unclear. To the authors' knowledge, there
      are only 14 cases of familial gastroschisis in the literature. The authors add
      the second case of mother-and-son occurrence and a case of siblings occurrence,
      thereby updating the current literature for family gastroschisis.

PMID- 15852296
TI  - Aortoesophageal fistula as a complication of Montgomery salivary bypass tube.
AB  - The authors describe a 2-year-old girl with a right-sided aortic arch who
      developed a sudden, fatal aortoesophageal fistula after prolonged placement of
      Montgomery salivary bypass tubes in the distal esophagus.

PMID- 15852297
TI  - Acute phlegmonous gastritis in an infant.
AB  - The authors present a case of acute phlegmonous gastritis occurring in an 11
      month-old infant in whom the diagnosis was made by microscopic examination after
      surgery for perforation of the stomach. The patient recovered uneventfully. The
      pathogenesis, diagnosis, and treatment in this inflammatory process are
      discussed.

PMID- 15852298
TI  - The role of the surgeon in the case of a giant neck mass in the EXIT procedure.
AB  - Large fetal neck masses can present a major challenge to securing an airway at
      birth, with associated risks of hypoxia, brain injury, and death. The authors
      report a case of a giant neck mass, diagnosed in a fetus of 28 weeks, treated
      through ex utero intrapartum treatment procedure to assist in securing an airway
      followed by excision of the mass on the day after delivery. A multidisciplinary
      team approach, combined with an accurate prenatal diagnosis obtained through
      fetal ultrasound magnetic resonance imaging examination, was the key to a
      successful outcome. The role of the pediatric surgeon was initially to secure the
      airways through a tracheostomy followed by excision of the mass when the infant's
      vital parameters had been stabilized.

PMID- 15852299
TI  - Our minimally invasive approach to pectus excavatum.

PMID- 15852300
TI  - Proteome analysis of human hepatocellular carcinoma tissues by two-dimensional
      difference gel electrophoresis and mass spectrometry.
AB  - Proteome analysis of human hepatocellular carcinoma tissues was conducted using
      two-dimensional difference gel electrophoresis coupled with mass spectrometry.
      Paired samples from the normal and tumor region of resected human liver were
      labeled with Cy3 and Cy5, respectively while the pooled standard sample was
      labeled with Cy2. After analysis by the DeCyder software, protein spots that
      exhibited at least a two-fold difference in intensity were excised for in-gel
      tryptic digestion and matrix-assisted laser desorption/ionization-time of flight
      mass spectrometry. A total of 6 and 42 proteins were successfully identified from
      the well- and poorly-differentiated samples, respectively. The majority of these
      proteins are related to detoxification/oxidative stress and metabolism. Three
      down-regulated metabolic enzymes, methionine adenosyltransferase, glycine N
      methyltransferase, and betaine-homocysteine S-methyltransferase that are involved
      in the methylation cycle in the liver are of special interest. Their expression
      levels, especially, methionine adenosyltransferase, seemed to have a major
      influence on the level of S-adenosylmethionine (AdoMet), a vital intermediate
      metabolite required for the proper functioning of the liver. Recent work has
      shown that chronic deficiency in AdoMet in the liver results in spontaneous
      development of steatohepatitis and hepatocellular carcinoma, and hence the down
      regulation of hepatic methionine adenosyltransferase in our hepatocellular
      carcinoma samples is in line with this observation. Moreover, when a comparison
      is made between the differentially expressed proteins from our human
      hepatocellular carcinoma samples and from the liver tissues of knockout mice
      deficient in methionine adenosyltransferase, there is a fairly good correlation
      between them.

PMID- 15852301
TI  - Effects of excluded volume and polydispersity on solution properties of lentinan
      in 0.1 M NaOH solution.
AB  - Seven lentinan fractions of various weight-average molecular weights (M(w)),
      ranging from 1.45 x 10(5) to 1.13 x 10(6) g mol(-1) were investigated by static
      light scattering and viscometry in 0.1M NaOH solution at 25 degrees C. The
      intrinsic viscosity [eta] - M(w) and radius of gyration s(2)(z) (1/2) - M(w)
      relationships for lentinan in 0.1M NaOH solution were found to be represented by
      [eta] = 5.1 x 10(-3)M(w) (0.81) cm(3) g(-1) and s(2)(z) (1/2) = 2.3 x 10(-1)M(w)
      (0.58) nm, respectively. Focusing on the effects of the M(w) polydispersity with
      the Schulz-Zimm distribution function, the data of M(w), s(2)(z) (1/2), and [eta]
      was analyzed on the basis of the Yoshizaki-Nitta-Yamakawa theory for the
      unperturbed helical wormlike chain combined with the quasi-two-parameter (QTP)
      theory for excluded-volume effects. The persistence length, molecular weight per
      unit contour length, and the excluded-volume strength were determined roughly to
      be 6.2 nm, 980 nm(-1), and 0.1, respectively. Compared with the theoretical value
      calculated by the Monte Carlo model, the persistence length is longer than that
      of the single (1 --> 3)-beta-(D)-glucan chain. The results revealed that lentinan
      exists as single-stranded flexible chains in 0.1M NaOH solution with a certain
      degree of expansion due to the electrostatic repulsion from the interaction
      between the OH(-) anions and lentinan molecules.

PMID- 15852302
TI  - Enantioseparation by HPLC using phenylcarbonate, benzoylformate, p
      toluenesulfonylcarbamate, and benzoylcarbamates of cellulose and amylose as
      chiral stationary phases.
AB  - Phenylcarbonate, benzoylformate, and p-toluenesulfonylcarbamate of cellulose and
      five new benzoylcarbamate derivatives of both cellulose and amylose were
      synthesized and their chiral recognition abilities were evaluated as chiral
      stationary phases (CSPs) for high-performance liquid chromatography (HPLC).
      Cellulose benzoylcarbamate has a higher chiral recognition ability compared to
      phenylcarbonate, p-toluenesulfonylcarbamate, and benzoylformate of cellulose. The
      benzoylcarbamate derivatives exhibited a characteristic chiral recognition for
      the racemates, which bear a hydrogen atom capable of hydrogen bonding to the
      carbonyl group of the benzoylcarbamates. The structures of the benzoylcarbamates
      were investigated by CD spectroscopy.

PMID- 15852303
TI  - Chiral recognition of cyclic alpha-hydroxyketones by CD-sensitive zinc
      tetraphenylporphyrin tweezer.
AB  - A combined chemical/chiroptical microscale protocol for the determination of
      absolute configurations of cyclic alpha-hydroxyketones is described. The hydroxyl
      group in cyclic alpha-hydroxyketones is converted into (3
      aminopropylamino)acetate (NH2CH2CH2CH2NHCH2COOR), or more generally, according to
      a newly developed protocol, into (3-hydroxypropylamino)acetate group
      (HOCH2CH2CH2NHCH2COOR). The resultant conjugated compound forms a 1:1 host-guest
      complex with a dimeric zinc porphyrin tweezer, which exhibits exciton-coupled
      bisignate CD spectrum centered around the 420-nm porphyrin Soret band due to
      induced helicity between the two porphyrins in the complex. The absolute
      configurations of the alpha-stereogenic center is then determined by comparison
      of the sign of the observed CD exciton couplet of the complex with that of the
      preferred porphyrin twist predicted by the Merck Molecular Force Field (MMFFs)
      method.

PMID- 15852304
TI  - Relationship between enzyme activity and dimeric structure of recombinant HIV-1
      reverse transcriptase.
AB  - The multifunctional enzyme human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) is a heterodimer composed of a 66-kDa (p66) subunit and a p66
      derived 51-kDa (p51) subunit. p66/p51 HIV-1 RT contains 1 functional DNA
      polymerase and 1 ribonuclease H (RNase H) active site, which both reside in the
      p66 subunit at spatially distinct regions. In this study, we have investigated
      the relationship between the heterodimeric structure of HIV-1 RT and its
      enzymatic properties by introducing mutations at RT codon W401 that inhibit the
      formation of p66/p51 heterodimers. We demonstrate a striking correlation between
      abrogation of both HIV-1 RT dimerization and DNA polymerase activity. In
      contrast, the p66 monomers exhibited only moderately slowed catalytic rates of
      DNA polymerase-dependent and DNA polymerase-independent RNase H cleavage activity
      compared with the wild-type (WT) enzyme. Furthermore, no major changes in the
      unique cleavage patterns were observed between the WT and mutant enzymes for the
      different substrates used in the RNase H cleavage assays. Based on these results,
      and on our current understanding of HIV-1 RT structure, we propose that the p66
      monomer can adopt an open tertiary conformation that is similar to that observed
      for the subunit in the heterodimeric enzyme. We also propose that the formation
      of intersubunit interactions in HIV-1 RT regulates the establishment of a
      functional DNA polymerase active site.

PMID- 15852305
TI  - A consistent set of statistical potentials for quantifying local side-chain and
      backbone interactions.
AB  - The frequencies of occurrence of atom arrangements in high-resolution protein
      structures provide some of the most accurate quantitative measures of interaction
      energies in proteins. In this report we extend our development of a consistent
      set of statistical potentials for quantifying local interactions between side
      chains and the polypeptide backbone, as well as nearby side-chains. Starting with
      phi/psi/chi1 propensities that select for optimal interactions of the 20 amino
      acid side-chains with the 2 flanking peptide bonds, the following 3 new terms are
      added: (1) a distance-dependent interaction between the side-chain at i and the
      carbonyl oxygens and amide protons of the peptide units at i +/- 2, i +/- 3, and
      i +/- 4; (2) a distance-dependent interaction between the side-chain at position
      i and side-chains at positions i + 1 through i + 4; and (3) an orientation
      dependent interaction between the side-chain at position i and side-chains at i +
      1 through i + 4. The relative strengths of these 4 pseudo free energy terms are
      estimated by the average information content of each scoring matrix and by
      assessing their performance in a simple fragment threading test. They vary from 
      0.4 - -0.5 kcal/mole per residue for phi/psi/chi1 propensities to a range of 
      0.15 - -0.6 kcal/mole per residue for each of the other 3 terms. The combined
      energy function, containing no interactions between atoms more than 4 residues
      apart, identifies the correct structural fragment for randomly selected 15 mers
      over 40% of the time, after searching through 232,000 alternative conformations.
      For 14 out of 20 sets of all-atom Rosetta decoys analyzed, the native structure
      has a combined score lower than any of the 1700-1900 decoy conformations. The
      ability of this energy function to detect energetically important details of
      local structure is demonstrated by its power to distinguish high-resolution
      crystal structures from NMR solution structures.

PMID- 15852306
TI  - Enhanced sampling near the native conformation using statistical potentials for
      local side-chain and backbone interactions.
AB  - In the preceding article in this issue of Proteins, an empirical energy function
      consisting of 4 statistical potentials that quantify local side-chain-backbone
      and side-chain-side-chain interactions has been demonstrated to successfully
      identify the native conformations of short sequence fragments and the native
      structure within large sets of high-quality decoys. Because this energy function
      consists entirely of interactions between residues separated by fewer than 5
      positions, it can be used at the earliest stage of ab initio structure prediction
      to enhance the efficiency of conformational search. In this article, protein
      fragments are generated de novo by recombining very short segments of protein
      structures (2, 4, or 6 residues), either selected at random or optimized with
      respect this local energy function. When local energy is optimized in selected
      fragments, more efficient sampling of conformational space near the native
      conformation is consistently observed for 450 randomly selected single turn
      fragments, with turn lengths varying from 3 to 12 residues and all 4 combinations
      of flanking secondary structure. These results further demonstrate the energetic
      significance of local interactions in protein conformations. When used in
      combination with longer range energy functions, application of these potentials
      should lead to more accurate prediction of protein structure.

PMID- 15852307
TI  - Crystal packing effects on protein loops.
AB  - The effects of crystal packing on protein loop structures are examined by (1) a
      comparison of loops in proteins that have been crystallized in alternate packing
      arrangements, and (2) theoretical prediction of loops both with and without the
      inclusion of the crystal environment. Results show that in a minority of cases,
      loop geometries are dependent on crystal packing effects. Explicit representation
      of the crystal environment in a loop prediction algorithm can be used to model
      these effects and to reconstruct the structures, and relative energies, of a loop
      in alternative packing environments. By comparing prediction results with and
      without the inclusion of the crystal environment, the loop prediction algorithm
      can further be used to identify cases in which a crystal structure does not
      represent the most stable state of a loop in solution. We anticipate that this
      capability has implications for structural biology.

PMID- 15852308
TI  - Foregut glands of Solenogastres (mollusca): anatomy and revised terminology.
AB  - In the molluscan class Solenogastres, different types of foregut glands vary in
      number, structure, and location within the foregut. The present article describes
      their anatomy and cytology and intends to clarify their confused terminology.
      Pharyngeal glands, esophageal glands, and the more complex dorsal and
      ventrolateral foregut glands can be distinguished. The ventrolateral foregut
      glands (ventral foregut glandular organs, ventral salivary glands of auct.), in
      the literature subdivided previously into four types, are revisited here in the
      context of current vertebrate gland terminology. The results of recent
      investigations are added to earlier ones, and a classification system for these
      multicellular glands is proposed. This system is based on cytological characters
      of glandular cells (intra- or extraepithelial), characters of the associated
      musculature (inner or outer musculature), location of the gland relative to the
      pharynx epithelium (endoepithelial or exoepithelial), characters of the gland
      openings (paired or unpaired), morphology of the gland duct (simple or branched),
      and some additional features like the arrangement of glandular cells along the
      gland ducts. Gross morphology and anatomy of ventrolateral foregut glands
      constitute useful taxonomic characters in determining higher taxa (family level),
      and finer details of the anatomy and cytology are useful in determining lower
      levels (genus and species). Possible pathways for the evolution of the different
      gland types of Solenogastres in relation to foregut glands present in the other
      molluscan clades are presented. The importance of ventrolateral foregut gland
      characters for phylogenetic considerations within the Solenogastres is discussed.

PMID- 15852310
TI  - Anorexia nervosa: definition, epidemiology, and cycle of risk.
AB  - Anorexia nervosa is a debilitating psychiatric disorder with profound biological,
      psychological, and social consequences. After an initial evaluation of the most
      widely used diagnostic criteria for anorexia nervosa, this paper reviews genetic
      and environmental risk factors for the development of anorexia with special
      emphasis on gene environment interplay and the impact of adverse perinatal
      events.

PMID- 15852311
TI  - Translational approaches to understanding anorexia nervosa.
AB  - Translational research has fostered significant gains in neuroscience and
      psychiatry and has been identified by the NIMH as a "priority area" for further
      funding. As applied to anorexia nervosa (AN), "translational research" describes
      the application of principles and methodologies employed in related fields to
      advance the understanding, and ultimately treatment and prevention, of this
      disorder. Several promising areas of translational research in AN are identified.
      Such research, particularly when linked to a conceptual framework, offers the
      potential of lending much-needed novel insight into this challenging and
      enigmatic disorder.

PMID- 15852312
TI  - Neurobiology of anorexia nervosa: clinical implications of alterations of the
      function of serotonin and other neuronal systems.
AB  - Recent evidence suggests that genetic and neurobiologically mediated mechanisms
      contribute to the etiology of anorexia nervosa (AN). Serotonin neuronal systems,
      in particular, may create vulnerabilities related to pathological feeding,
      anxiety and obsessions, and extremes of impulse control, that make individuals
      susceptible to developing an eating disorder, perhaps in combination with
      environmental stressors.

PMID- 15852314
TI  - Assessment of anorexia nervosa.
AB  - Standardized assessment of anorexia nervosa (AN) is essential in research and can
      dramatically enhance clinical practice as well. This article highlights
      conceptual and practical considerations pertaining to the establishment and
      administration of an assessment battery for AN. Commonly utilized assessment
      measures are described briefly, and recommendations for advancing assessment of
      AN are provided.

PMID- 15852315
TI  - Evidence-based treatment of anorexia nervosa.
AB  - This paper addresses the question "Is evidence-based treatment of anorexia
      nervosa possible?" "Barely" is the conclusion drawn. New forms of treatment are
      needed for adults with anorexia nervosa, and the true value of family-based
      treatment for adolescents has yet to be established.

PMID- 15852316
TI  - Health services research in anorexia nervosa.
AB  - The present paper reviews studies of the delivery of health services for
      individuals with anorexia nervosa, utilizing four interrelated concepts that
      guide much of health services research: equity, effectiveness, efficiency, and
      economy. It identifies major gaps in knowledge regarding health services
      utilization and costs.

PMID- 15852317
TI  - A community-based training program for eating disorders and its contribution to a
      provincial network of specialized services.
AB  - The Ontario Community Outreach Program for Eating Disorders is a pilot training
      project within the eating disorder programs at the University Health Network-
      Toronto General Hospital (TGH) and the Hospital for Sick Children. This system
      provides ongoing training, consultation, and research evaluation in areas ranging
      from prevention through to tertiary care, in the hopes of increasing the capacity
      of practitioners to respond to the healthcare pressures of those experiencing
      eating disorders. A total of 3,315 health care practitioners and educators in
      Ontario participated in community-based training workshops. A pre-post analysis
      of participants' self-report evaluations was conducted using chi-square analyses.
      The findings revealed that there was a statistically significant increase in
      participants' (a) knowledge of eating disorders and of body image issues and (b)
      level of comfort to either treat clients with eating disorders or teach a
      curriculum on body image. The contribution of the training program to the
      development of a provincial network of specialized eating disorder services,
      designed to promote the public's access to timely and appropriate care for the
      full spectrum of eating disorders, are discussed.

PMID- 15852319
TI  - A review and primer of molecular genetic studies of anorexia nervosa.
AB  - Recent research on anorexia nervosa (AN) has focused on examining the genetic
      underpinnings of its etiology. The current article reviews molecular genetic
      studies that have focused on this aspect of AN development. Medline and PsychInfo
      literature searches, in addition to close inspection of study reference sections,
      were used to identify studies that examined the genetic diathesis for AN.
      Findings from association studies indicate some role for the serotonin system in
      the development of AN. Genomic regions on chromosomes 1 and 10 are also likely to
      harbor susceptibility genes for AN as well as a range of eating pathologies.
      Findings corroborate those of neurobiologic studies suggesting that alterations
      in serotonergic functioning may contribute to the pathogenesis of AN.
      Nonetheless, future molecular genetic research would benefit from larger and more
      sustained investigations of candidate genes in homogeneous phenotypes.

PMID- 15852320
TI  - Functional neuroimaging in early-onset anorexia nervosa.
AB  - Previous neuroimaging studies in early-onset anorexia nervosa provide evidence of
      limbic system dysfunction. The current study adds support to the possibility by
      revealing a significant association between unilateral reduction of blood flow in
      the temporal region and impaired visuospatial ability, impaired visual memory,
      and enhanced speed of information processing.

PMID- 15852321
TI  - Medical complications in adolescents with anorexia nervosa: a review of the
      literature.
AB  - The purpose of the current article is to summarize the evidence-based medical
      complications and treatments that are both common and unique to adolescents with
      anorexia nervosa (AN). Recent literature relating to the cardiovascular
      complications, refeeding syndrome, alterations in linear growth, impaired bone
      mineral accretion, and structural and functional brain changes was reviewed. The
      literature suggests that the medical complications in adolescents with AN are
      different from those reported in adults. The unique clinical presentation, the
      early onset, and the unknown impact of these complications underscore the need
      for early identification and treatment of AN in adolescents. AN is a serious
      disorder with significant and often life-threatening medical complications. The
      increasing growth of evidence highlights the importance of early identification
      and treatment by an interdisciplinary team of health care providers who have
      expertise in managing adolescents with AN and their medical sequelae.

PMID- 15852322
TI  - Pharmacologic treatment of anorexia nervosa: where do we go from here?
AB  - Anorexia nervosa (AN) is a serious mental disorder, characterized by severely low
      weight and cognitive distortions about body shape and weight. AN is generally
      associated with a range of psychological symptoms, including depression, anxiety,
      obsessions, and rituals. The current study summarized findings from randomized
      controlled trials (RCT) using pharmacologic treatments in patients with AN. We
      conducted a review of literature using Medline. Several classes of pharmacologic
      agents have been studied in small samples of patients with acute AN without
      finding clear benefit to eating, weight, body shape concerns, or associated
      psychopathology. Studies have been limited by small sample sizes, as well as by
      research design with most studies adding medication to comprehensive hospital
      based treatment programs. Future directions for pharmacologic treatment research
      in AN should include outpatient trials, rigorous study of atypical antipsychotic
      medication, and assessment of medication effect for relapse prevention in weight
      restored patients.

PMID- 15852323
TI  - Family-based treatment of eating disorders.
AB  - The current article provides a brief description of the theory and empirical
      support for family treatment of eating disorders. The main literature related to
      family treatment for anorexia nervosa (AN) and bulimia nervosa (BN) is reviewed
      and the findings highlighted. Family treatment, particularly as devised by
      researchers at the Maudsley Hospital, appears to be an effective treatment for
      adolescents with short-term AN. It also may be an appropriate treatment for BN in
      the same age group, although evidence for this is in much shorter supply. Data
      support the use of family treatments for adolescents with eating disorders.
      Controlled trials and other systematic research are needed to determine whether
      family treatment is the best approach.

PMID- 15852324
TI  - Personality and anorexia nervosa.
AB  - We provided a selective review of the relationship between anorexia nervosa (AN)
      and personality. They reviewed the existing empirical literature examining the
      relationship between AN and personality. In spite of continued methodologic
      challenges related to personality assessment, there appears to be a relatively
      common phenotype in restricting-type AN characterized by high degrees of
      obsessionality, restraint, and perfectionism. However, there is also evidence of
      variability within the AN diagnostic category that is related to personality
      variables. Importantly, personality variables may significantly predict the
      course and outcome of AN. Personality variables may be risk factors for AN,
      consequences of AN, share a common cause with AN, or affect the course and
      outcome of AN. This literature would be enhanced by the articulation of
      conceptual models of these relationships that can be empirically tested.

PMID- 15852325
TI  - Neuropsychological studies in anorexia nervosa.
AB  - Neuropsychological findings in eating disorders are somewhat inconsistent. This
      may be because individual studies have used a broad range of tests on relatively
      small, heterogeneous clinical groups, thus limiting the detection of subtle
      neuropsychological differences in these patients. Therefore, rather than using
      broad assessments of a variety of neuropsychological functions, adoption of a
      more focused, hypothesis-driven approach based on clinical practice is proposed.
      This will allow more in-depth investigations of targeted functions and will
      improve the chances of detecting a problem, of exploring its ecologic validity,
      and of tailoring a treatment. We have demonstrated this approach using our
      neuropsychological studies of cognitive flexibility in anorexia nervosa (AN).

PMID- 15852326
TI  - Parenting concerns of women with histories of eating disorders.
AB  - The current article reviews the literature on parenting among women with EDs, and
      outlines the process of developing an intervention addressing their parenting
      concerns.

PMID- 15852327
TI  - The process of recovery in eating disorder sufferers' own words: an Internet
      based study.
AB  - This exploratory Internet-based study attempts to understand what eating disorder
      sufferers suggest when they mention the word recovery. All messages (N = 685)
      posted in a Finnish-language eating disorders discussion group during a 3-month
      period were analyzed for the contexts of the word recovery using text analysis
      software and qualitative methods. The discussion group participants' views of
      recovery changed according to their current stage of change. Mentioning recovery
      was least likely during precontemplation and relapse. Internet discussion group
      was seen as helpful in the early stages of change, but as impeding recovery in
      the last stages. Willpower and ceasing to identify with eating disorders were
      viewed as essential to recovery. The value of professional help in recovery was
      viewed as conditional on the eating disorders sufferer's own willingness to
      change. Internet-based support groups have many potential therapeutic
      applications. Motivational aspects need to be taken into account in promoting
      recovery.

PMID- 15852329
TI  - The future of treatment research in anorexia nervosa.
AB  - In spite of much being written on the treatment of anorexia nervosa (AN), and the
      well-documented long-term morbidity of this illness, treatment effects have been
      little investigated. The current article considers the prospects for treatment
      research, taking note of the formidable challenges that lie ahead for the design,
      implementation, and interpretation of controlled clinical trials, and
      highlighting opportunities for effectiveness studies. In the light of increasing
      evidence of the role played by biologic susceptibility factors in AN, the
      potential future contribution to treatment research of advances in
      pharmacogenetics and molecular neuroscience also receives comment.

PMID- 15852330
TI  - Diagnostic criteria for anorexia nervosa: looking ahead to DSM-V.
AB  - In considering possible revisions to the diagnostic criteria for anorexia nervosa
      (AN), questions can be raised regarding the 85% cutoff and consideration could be
      given to using a body mass index (BMI) score instead. The criterion most likely
      to change in the 4th ed. of the Diagnostic and Statistical Manual of Mental
      Disorders (Washington, DC: American Psychiatric Association) is the amenorrhea
      criterion because this does not appear to add to the diagnostic specificity.

PMID- 15852331
TI  - Research training in anorexia nervosa.
AB  - Training of new investigators is critical to promoting research in anorexia
      nervosa. Obstacles to training are noted, examples of current research training
      and early career funding opportunities are discussed, and suggestions to support
      training are offered.

PMID- 15852332
TI  - Federal advocacy for anorexia nervosa: an American model.
AB  - Advocacy efforts aimed at influencing federal policy are needed to strengthen
      accessible resources for anorexia nervosa (AN) and to improve treatment and
      prevention. Federal advocacy in the United States is spearheaded by the Eating
      Disorders Coalition for Research, Policy, and Action (EDC) whose mission is to
      advance the federal recognition of eating disorders as a public health priority.

PMID- 15852333
TI  - Discrimination of single-nucleotide alterations by G-specific fluorescence
      quenching.
AB  - A new strategy for the detection of single-base alterations through fluorescence
      quenching by guanine (G) is described. We have devised a novel base
      discriminating fluorescent (BDF) nucleoside, 4'PyT, that contains a
      pyrenecarboxamide fluorophore at the thymidine sugar's C4'-position. 4'PyT
      containing oligodeoxynucleotides only exhibited enhanced fluorescence in response
      to the presence of a complementary adenine base. In contrast, the fluorescence of
      mismatched duplexes containing 4'PyT/N base pairs (N = C, G, or T) was
      considerably weaker. This highly A-selective fluorescence was a product of
      guanine-specific quenching efficiency; when the complementary base to 4'PyT was a
      mismatch, the pyrenecarboxamide fluorophore was able to interact intimately with
      neighboring G bases (the most likely interaction in the case of intercalation),
      so effective quenching by the G bases occurred in the mismatched duplexes. In
      contrast, duplexes containing 4'PyT/A base pairs exhibited strong emission, since
      in this case the fluorophores were positioned in the minor groove and able to
      escape fluorescence quenching by the G bases.

PMID- 15852334
TI  - Bacterial cell penetration by beta3-oligohomoarginines: indications for passive
      transfer through the lipid bilayer.

PMID- 15852335
TI  - From virtual to real screening for D3 dopamine receptor ligands.

PMID- 15852336
TI  - Regulating enzyme activities in a multiple-enzyme complex.

PMID- 15852337
TI  - Quantum dots protected with tiopronin: a new fluorescence system for cell-biology
      studies.

PMID- 15852338
TI  - Validation of commonly used immunostains on cell-transferred cytologic specimens.
AB  - BACKGROUND: Immunocytochemical staining (ICC) is often limited by the lack of
      cell blocks that contain diagnostic cells or by the unavailability of smear
      materials. The cell-transfer technique, in which original smear material is
      divided into several pieces and then transferred to multiple slides, can
      facilitate multiple ICC on limited materials. However the reliability of the
      staining results has not been systematically evaluated. METHODS: The authors
      validated 21 commonly used antibodies (cytokeratin [CK] 7, CK 20, TTF-1, panCK,
      vimentin, HMB-45, Mart-1, leukocyte common antigen, chromogranin, synaptophysin,
      estrogen receptor, progesterone receptor, prostate-specific antigen, prostatic
      acid phosphatase, calretinin, CK5/6, WT-1, BerEP4, MOC-31, p63, and
      thyroglobulin) on the cell-transferred materials of various tumor samples (n =
      20) and reactive effusion samples (n = 2). The staining results were compared
      with the previously available ICC results (performed either on cell block
      sections or on smears) of the same specimens. RESULTS: One hundred pieces of
      transferred materials were immunostained, of which 5 (5%) were lost during the
      staining procedure. Of the remaining 95 pieces, 92 (97%) showed staining results
      that agreed with those of the previous ICC, whereas 3 (3%) showed results that
      disagreed. The original ICC in the latter three specimens was performed on cell
      block sections and showed focally positive synaptophysin staining in a sample
      with a neuroendocrine tumor, focally positive CK5/6 staining in a pleural
      effusion sample with mesothelioma, and positive TTF-1 staining in a lymph node
      sample with metastatic lung carcinoma. Their corresponding ICC of cell
      transferred materials showed negative results. An increase in background staining
      was observed in 1 of the 95 tissue pieces, but no false-positive results were
      observed. CONCLUSIONS: In general, ICC can be reliably performed on cell
      transferred tissue specimens for markers tested. However, caution should be taken
      when interpreting ICC results in tissue specimens with limited cellularity and
      heavy background staining.

PMID- 15852339
TI  - High abundance protein profiling of cystic fibrosis lung epithelial cells.
AB  - Protein profiles of cultured cystic fibrosis (CF) lung epithelial cells were
      analyzed by two-dimensional gel electrophoresis and mass spectrometry (MS). The
      analysis gave rise to a protein map over the pI range of 4-7, and a molecular
      weight range of ca. 100-10 kDa. The map contains 194 identified proteins, which
      were detectable by silver stain. All silver stained features were identified by
      matrix-assisted laser desorption/ionization-time of flight MS of tryptic
      peptides. Some proteins were found to be represented by multiple features on the
      2-D gel. Among the high abundance proteins identified were sets of proteins
      associated with inflammation, including the classical NFkappaB, p65 (RelA) and
      NFkappaB, p65 (RelB). We suggest that this composite atlas of the high abundance
      CF lung epithelial proteome will serve as a reference database for future studies
      of candidate CF drugs, validating different approaches to CFTR gene therapy, and
      analogous investigations of other types of human lung disorders.

PMID- 15852340
TI  - Proteome analysis of Escherichia coli using high-performance liquid
      chromatography and Fourier transform ion cyclotron resonance mass spectrometry.
AB  - The basic problem of complexity poses a significant challenge for proteomic
      studies. To date two-dimensional gel electrophoresis (2-DE) followed by enzymatic
      in-gel digestion of the peptides, and subsequent identification by mass
      spectrometry (MS) is the most commonly used method to analyze complex protein
      mixtures. However, 2-DE is a slow and labor-intensive technique, which is not
      able to resolve all proteins of a proteome. To overcome these limitations gel
      free approaches are developed based on high performance liquid chromatography
      (HPLC) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR
      MS). The high resolution and excellent mass accuracy of FT-ICR MS provides a
      basis for simultaneous analysis of numerous compounds. In the present study, a
      small protein subfraction of an Escherichia coli cell lysate was prepared by size
      exclusion chromatography and proteins were analyzed using C4 reversed phase (RP)
      HPLC for pre-separation followed by C18 RP nanoHPLC/nanoESI FT-ICR MS for
      analysis of the peptide mixtures after tryptic digestion of the protein
      fractions. We identified 231 proteins and thus demonstrated that a combination of
      two RP separation steps - one on the protein and one on the peptide level - in
      combination with high-resolution FT-ICR MS has the potential to become a powerful
      method for global proteomics studies.

PMID- 15852341
TI  - Proteomic analysis of the expression of proteins related to rice quality during
      caryopsis development and the effect of high temperature on expression.
AB  - Proteins are essential to rice caryopsis development and quality formation. High
      temperature is an important environmental factor, which may decrease grain
      quality. In the present study rice caryopsis proteins were profiled by two
      dimensional polyacrylamide gel electrophoresis, and differentially expressed
      proteins were analyzed by liquid chromatography/tandem mass spectrometry.
      Expressions of more than 400 polypeptide spots during caryopsis development, in
      response to temperature treatments or between varieties were monitored. Among
      them, more than 70 differentially expressed polypeptides were analyzed by liquid
      chromatography/tandem mass spectrometry. We identified 54 proteins with known
      functions. Of these, 21 were involved with carbohydrate metabolism, 14 with
      protein synthesis and sorting, and 9 with stress responses. Waxy (Wx) proteins
      and glutelins were the most significant spots, which increased significantly
      during development. Allergen-like proteins, PPDK and NADH-SDH, also were
      expressed during development, implying their physiological roles in caryopsis.
      Expression of large isoforms of Wx proteins was correlated with the amylose
      content of rice caryopses. One protein with high GC content in its DNA sequence
      was correlated with the chalky trait of kernels. High temperature (35/30 degrees
      C) decreased the expression of Wx proteins, allergen-like proteins, and
      elongation factor 1beta, but increased the expression of small heat shock
      proteins (sHSP), glyceraldehyde-3-phosphate dehydrogenase, and prolamin. sHSP was
      positively correlated with the appearance of chalky kernels. During development,
      glutelins were phosphorylated and glycosylated, indicating that these molecules
      were post-translationally modified. Possible functions of the expression of
      candidate proteins on the grain quality are discussed.

PMID- 15852342
TI  - E7-expressing HaCaT keratinocyte cells are resistant to oxidative stress-induced
      cell death via the induction of catalase.
AB  - Cervical carcinoma is one of the most prevalent cancers in women worldwide, and
      human papillomavirus (HPV) type 16 is the most common agent linked to human
      cervical carcinoma. In order to identify various relevant factors affected by the
      E7 oncogene, we established a stable cell line, which constitutively expressed E7
      using the HaCaT human keratinocyte cell line. The increased expression and
      activity of catalase in the E7-expressing HaCaT cells (HaCaT/E7) were verified
      via matrix-assisted laser desorption/ionization-time of flight, Western blot, and
      reverse transcription-polymerase chain reaction analyses. The regulation of
      catalase by E7 was investigated by the detection of catalase promoter activity.
      E7 enhanced the activities of both the catalase promoter and nuclear factor
      kappaB, one of the major transcription factors regulating the expression of the
      catalase gene. HaCaT/E7 cells produced lower quantities of intracellular reactive
      oxygen species (ROS), and appeared to be more resistant to H(2)O(2)-induced cell
      death. Moreover, in order to test the specific effects of E7 on catalase
      induction, the HaCaT/E7 cells were transiently transfected with E7 antisense
      vector, resulting in reductions in both the expression and activity of catalase,
      and a recovery of intracellular ROS levels, thus resulting in recovered
      sensitivity to H(2)O(2)-induced cell death. These results suggest that the HPV 16
      E7 oncogene induces higher resistance to ROS-induced cell injury in the E7
      infected cells, probably via the modulation of several anti-oxidant enzymes,
      including catalase.

PMID- 15852344
TI  - Comprehensive proteomics in yeast using chromatographic fractionation, gas phase
      fractionation, protein gel electrophoresis, and isoelectric focusing.
AB  - We have investigated the use of a variety of different techniques to identify as
      many proteins as possible in a yeast lysate, with the aim of investigating the
      overlap and complementarity of data from different approaches. A standard lysate
      was prepared from log phase yeast (Saccharomyces cerevisiae). This was then
      subjected to analysis via five different approaches aimed at identifying as many
      proteins as possible using an ion trap mass spectrometer. The total number of non
      redundant protein identifications from each experiment was: 524 proteins by 2-D
      (SCX/C18) nanoflow liquid chromatography-liquid chromatography tandem mass
      spectrometry (nanoLC-LC MS/MS (MudPIT)); 381 proteins by nanoLC-MS/MS with gas
      phase fractionation by mass range selection; 390 proteins by nanoLC-MS/MS with
      gas phase fractionation by ion abundance selection; 898 proteins by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation of
      proteins, in-gel digestion, and nanoLC-MS/MS of gel slices; and 422 proteins by
      isoelectric focusing of proteins, in-gel digestion and nanoLC-MS/MS of gel
      slices. The total number of non-redundant protein identifications in the five
      experiments was 1204. Combining only the two best experiments, the SDS-PAGE gel
      slices and the Mudpit, produces 1024 proteins identified, more than 85% of the
      total. Clearly, combining a Mudpit analysis with an SDS-PAGE gel slice experiment
      gives the greatest amount of protein identification information from a limited
      amount of sample.

PMID- 15852345
TI  - Proteome analysis of brown spider venom: identification of loxnecrogin isoforms
      in Loxosceles gaucho venom.
AB  - Brown spiders of the Loxosceles genus are distributed worldwide. In Brazil, eight
      species are found in Southern states, where the envenomation by Loxosceles venom
      (loxoscelism) is a health problem. The mechanism of the dermonecrotic action of
      Loxosceles venom is not totally understood. Two isoforms of dermonecrotic toxins
      (loxnecrogins) from L. gaucho venom have been previously purified, and showed
      sequence similarities to sphingomyelinase. Herein we employed a proteomic
      approach to obtain a global view of the venom proteome, with a particular
      interest in the loxnecrogin isoforms' pattern. Proteomic two-dimensional gel
      electrophoresis maps for L. gaucho, L. intermedia, and L. laeta venoms showed a
      major protein region (30-35 kDa, pI 3-10), where at least eight loxnecrogin
      isoforms could be separated and identified. Their characterization used a
      combined approach composed of Edman chemical sequencing, matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry, and electrospray
      ionization-quadropole-time of flight tandem mass spectrometry leading to the
      identification of sphingomyelinases D. The venom was also pre-fractionated by gel
      filtration on a Superose 12 fast protein liqiud chromatography column, followed
      by capillary liquid chromatography-mass spectrometry. Eleven possible loxnecrogin
      isoforms around 30-32 kDa were detected. The identification of dermonecrotic
      toxin isoforms in L. gaucho venom is an important step towards understanding the
      physiopathology of the envenomation, leading to improvements in the immunotherapy
      of loxoscelism.

PMID- 15852343
TI  - A proteomic survey of rat cerebral cortical synaptosomes.
AB  - Previous findings from our laboratory and others indicate that two-dimensional
      gel electrophoresis (2-DE) can be used to study protein expression in defined
      brain regions, but mainly the proteins which are present in high abundance in
      glia are readily detected. The current study was undertaken to determine the
      protein profile in a synaptosomal subcellular fraction isolated from the cerebral
      cortex of the rat. Both 2-DE and liquid chromatography - tandem mass spectrometry
      (LC-MS/MS) procedures were used to isolate and identify proteins in the
      synaptosomal fraction and accordingly >900 proteins were detected using 2-DE; the
      167 most intense gel spots were isolated and identified with matrix-assisted
      laser desorption/ionization - time of flight peptide mass fingerprinting or LC
      MS/MS. In addition, over 200 proteins were separated and identified with the LC
      MS/MS "shotgun proteomics" technique, some in post-translationally modified form.
      The following classes of proteins associated with synaptic function were
      detected: (a) proteins involved in synaptic vesicle trafficking-docking (e.g.,
      SNAP-25, synapsin I and II, synaptotagmin I, II, and V, VAMP-2, syntaxin 1A and
      1B, etc.); (b) proteins that function as transporters or receptors (e.g.,
      excitatory amino acid transporters 1 and 2, GABA transporter 1); (c) proteins
      that are associated with the synaptic plasma membrane (e.g., post-synaptic
      density-95/synapse-associated protein-90 complex, neuromodulin (GAP-43), voltage
      dependent anion-selective channel protein (VDACs), sodium-potassium ATPase
      subunits, alpha 2 spectrin, septin 7, etc.); and (d) proteins that mediate
      intracellular signaling cascades that modulate synaptic function (e.g.,
      calmodulin, calcium-calmodulin-dependent protein kinase subunits, etc.). Other
      identified proteins are associated with mitochondrial or general cytosolic
      function. Of the two proteins identified as endoplasmic reticular, both interact
      with the synaptic SNARE complex to regulate vesicle trafficking. Taken together,
      these results suggest that the integrity of the synaptosomes was maintained
      during the isolation procedure and that this subcellular fractionation technique
      enables the enrichment of proteins associated with synaptic function. The results
      also suggest that this experimental approach can be used to study the
      differential expression of multiple proteins involved in alterations of synaptic
      function.

PMID- 15852346
TI  - Bacterial protein microarrays for identification of new potential diagnostic
      markers for Neisseria meningitidis infections.
AB  - Neisseria meningitidis is the most common cause of meningitis and causes epidemic
      outbreaks. One trait of N. meningitidis, which is associated with most of the
      currently recognized virulence determinants, is the presence of phase-variable
      genes that are suspected to enhance its ability to cause an invasive disease. To
      detect the immune responses to phase-variable expressed proteins, we applied
      protein microarray technology for the screening of meningitis patient sera. We
      amplified all 102 known phase-variable genes from N. meningitidis serogroup B
      strain MC58 by polymerase chain reaction and subcloned them for expression in
      Escherichia coli. With this approach, we were able to express and purify 67
      recombinant proteins representing 66% of the annotated genes. These were spotted
      robotically onto coated glass slides to generate protein microarrays, which were
      screened using 20 sera of patients suffering from meningitis, as well as healthy
      controls. From these screening experiments, 47 proteins emerged as immunogenic,
      exhibiting a variable degree of seroreactivity with some of the patient sera.
      Nine proteins elicited an immune response in more than three patients, with one
      of them, the phase-variable opacity protein OpaV (NMB0442), showing responses in
      11 patient sera. This is the first time that protein microarray technology has
      been applied for the investigation of genetic phase variation in pathogens. The
      identification of disease-specific proteins is a significant target in biomedical
      research, as such proteins may have medical, diagnostic, and commercial potential
      as disease markers.

PMID- 15852347
TI  - Proteomic identification of ubiquitinated proteins from human cells expressing
      His-tagged ubiquitin.
AB  - A proteomics method has been developed to purify and identify the specific
      proteins modified by ubiquitin (Ub) from human cells. In purified samples, Ub and
      21 other proteins were identified by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) spectra using SEQUEST. These proteins included several of
      the expected carriers of Ub including Ub-conjugating enzymes and histone
      proteins. To perform these experiments, a cell line coexpressing epitope tagged
      His(6X)-Ub and green fluorescent protein (GFP) was generated by stably
      transfecting HEK293 cells. Ubiquitinated proteins were purified using nickel
      affinity chromatography and digested in solution with trypsin. Complex mixtures
      of peptides were separated by reversed phase chromatography and analyzed by nano
      LC-MS/MS using the LCQ quadrupole ion-trap mass spectrometer. Proteins identified
      from His(6X)-Ub-GFP transfected cells were compared to a list of proteins from
      HEK293 cells, which associate with nickel-nitrilotriacetic acid (Ni-NTA)-agarose
      in the absence of His-tagged Ub. In a proof of principle experiment, His(6X)-Ub
      GFP transfected cells were treated with As (III) (10 microM, 24 h) in an attempt
      to identify substrates increasingly modified by Ub. In this experiment,
      proliferating cell nuclear antigen, a DNA repair protein and known ubiquitin
      substrate, was confidently identified. This proteomics method, developed for the
      analysis of ubiquitinated proteins, is a step towards large-scale
      characterization of Ub-protein conjugates in numerous physiological and
      pathological states.

PMID- 15852348
TI  - Autopolyploidy in cabbage (Brassica oleracea L.) does not alter significantly the
      proteomes of green tissues.
AB  - Polyploidization is a major evolutionary process in eukaryotes. In plants,
      genetic and epigenetic changes occur rapidly after formation of allopolyploids.
      Hybridization, rather than genome doubling itself, is considered as the main
      cause for the resulting differential gene expression. We studied the consequences
      of genome doubling alone in an autopolyploid model, by comparing two-dimensional
      gel electrophoresis (2-DE) gels of haploid, diploid, and tetraploid Brassica
      oleracea cabbages. Two fully homozygous lines, HDEM and RC, as well as two
      organs, leaf and stem, were studied. For the 558 common spots found present in
      all the 29 2-DE gels of the experiment, inter-organ and -genotype differences
      were the major sources of the variation in protein amounts: 41 and 10-13%,
      respectively. HDEM leaf and stem proteomes were not significantly affected by the
      ploidy level, since no qualitative variation was detected and since the number of
      quantitative variations could be due to chance. For RC, no qualitative variations
      were observed, but a few spots were significantly variable in protein amount.
      However, the number of inter-ploidy variations was of the same range as the
      number of intra-ploidy variations. In conclusion, whatever the ploidy level, leaf
      and stem proteomes remained globally unchanged in both cabbage lines.

PMID- 15852349
TI  - On-line isotachophoretic preconcentration and gel electrophoretic separation of
      sodium dodecyl sulfate-proteins on a microchip.
AB  - A microchip for integrated isotachophoretic (ITP) preconcentration with gel
      electrophoretic (GE) separation to decrease the detectable concentration of
      sodium dodecyl sulfate (SDS)-proteins was developed. Each channel of the chip was
      designed with a long sample injection channel to increase the sample loading and
      allow stacking the sample into a narrow zone using discontinuous ITP buffers. The
      pre-concentrated sample was separated in GE mode in sieving polymer solutions.
      All the analysis steps including injection, preconcentration, and separation of
      the ITP-GE process were performed continuously, controlled by a high-voltage
      power source with sequential voltage switching between the analysis steps.
      Without deteriorating the peak resolution, four SDS-protein analyses with
      integrated ITP-GE system resulted in a decreased detectable concentration of
      approximately 40-fold compared to the GE mode only. A good calibration curve for
      molecular weights of SDS-proteins indicated that the integrated ITP-GE system can
      be used for qualitative analysis of unknown protein samples.

PMID- 15852350
TI  - Aperiodic capillary electrophoresis method using an alternating current electric
      field for separation of macromolecules.
AB  - Switching from direct current (DC) to alternating current (AC) electric fields
      has provided substantial improvements in various instrument techniques that use
      electric fields for manipulating with various liquid-based systems. For example,
      AC fields are now used in both light scattering and electroacoustic instruments
      for measuring xi-potential, largely replacing more traditional
      microelectrophoresis techniques that use DC fields. In this paper, we suggest a
      novel way to make a similar transition in the area of separation techniques,
      capillary electrophoresis (CE) in particular. Dielectrophoresis is one well-known
      separation effect in which a drifting motion of particles is produced in a
      "spatially nonhomogeneous" AC electric field. However, there is another field
      effect that also causes a similar drift of particles. Instead of a "spatially
      nonhomogeneous" field, this method relies on a "temporally nonhomogeneous" field,
      normally referred to as "aperiodic electrophoresis". Despite a number of recently
      published experimental and theoretical papers describing this effect, it is less
      well-known than dielectrophoresis. We present a short overview of some of the
      relevant papers. We point out for the first time the idea that "aperiodic
      electrophoresis" might be useful for separation of macromolecules. We suggest
      several new mechanisms that could induce this effect in a sufficiently strong AC
      electric field. This effect can be used as a basis for a new separation method
      having several important advantages over traditional CE. We present a simple
      scheme as an example illustrating this new method.

PMID- 15852351
TI  - Separation of small peptides by electrochromatography on silica-based reversed
      phases and hydrophobic anion exchange phases.
AB  - Peptide separations are regarded as a promising application of capillary
      electrochromatography (CEC) and, at the same time, a suitable model to elucidate
      its mixed separation mechanism when charged analytes are involved. In this paper,
      studies on the separation of small peptides (2-4 amino acids) on a Spherisorb
      octadecyl silane (ODS) phase at acidic pH and on a strong anion exchange
      (SAX)/C18 mixed mode phase at weakly basic pH are reported. For the ODS phase a
      comparison of CEC, capillary zone electrophoresis (CZE) and high-performance
      liquid chromatography (HPLC) under identical buffer/eluent conditions is
      presented. The predicted retention factors for CEC under the assumption of simple
      superposition of HPLC retention and CZE migration matched the measured results
      for the peptides that had small retention factors in HPLC. For both types of
      stationary phases, a variation of the acetonitrile content in the mobile phase
      led to a wide range of retention factors, including negative values when co
      electroosmotic migration was dominant. Though both the ODS and the SAX/C18 phase
      offer unique advantages, the SCX/C18 phase at pH 9 provides more flexibility to
      alter separation selectivity for the selected peptides.

PMID- 15852352
TI  - On-line concentration of peptides and proteins with the hyphenation of polymer
      monolithic immobilized metal affinity chromatography and capillary
      electrophoresis.
AB  - An iminodiacetic acid (IDA)-type adsorbent is prepared at the one end of a
      capillary by covalently bonding IDA to the monolithic rods of macroporous
      poly(glycidyl methacrylate-co-ethylene dimethacrylate). Cu(II) is later
      introduced to the support via the interaction with IDA. By this means, polymer
      monolithic immobilized metal affinity chromatography (IMAC) materials are
      prepared. With such a column, IMAC for on-line concentration and capillary
      electrophoresis (CE) for the subsequent analysis are hyphenated for the analysis
      of peptides and proteins. The reproducibility of such a column has been proved
      good with relative standard deviations (RSDs) of dead time of less than 5% for
      injection-to-injection and 12% for column-to-column (n = 3). Through application
      on the analysis of standard peptides and real protein samples, such a technique
      has shown promising in proteome study.

PMID- 15852353
TI  - Development of migration models for acids in capillary electrophoresis using
      heuristic and radial basis function neural network methods.
AB  - A quantitative structure-mobility relationship (QSMR) was developed for the
      absolute mobilities of a diverse set of 277 organic and inorganic acids in
      capillary electrophoresis based on the descriptors calculated from the structure
      alone. The heuristic method (HM) and the radial basis function neural networks
      (RBFNN) were utilized to construct the linear and nonlinear prediction models,
      respectively. The prediction results were in agreement with the experimental
      values. The HM model gave a root-mean-square (RMS) error of 3.66 electrophoretic
      mobility units for the training set, 4.67 for the test set, and 3.88 for the
      whole data set, while the RBFNN gave an RMS error of 2.49, 3.19, and 2.65,
      respectively. The heuristic linear model could give some insights into the
      factors that are likely to govern the mobilities of the compounds, however, the
      prediction results of the RBFNN model seem to be better than that of the HM.

PMID- 15852354
TI  - Contaminant-induced current decline in capillary array electrophoresis.
AB  - High-throughput capillary array electrophoresis (CAE) instruments for DNA
      sequencing suffer to varying degrees from read length degradation associated with
      electrophoretic current decline and inhibition or delay in the arrival of
      fragments at the detector. This effect is known to be associated with residual
      amounts of large, slow-moving fragments of template or genomic DNA carried
      through from sample preparation and sequencing reactions. Here, we investigate
      the creation and expansion of an ionic depletion region induced by overloading
      the capillary with low-mobility DNA fragments, and the effect of growth of this
      region on electrophoresis run failure. Slow-moving fragments are analytically and
      experimentally shown to reduce the ionic concentration of the downstream
      electrolyte. With injection of large fragments beyond a threshold quantity, the
      anode-side boundary of the nascent depletion region begins to propagate toward
      the anode at a rate faster than the contaminant DNA migration. Under such
      conditions, the depletion region expands, the capillary current declines
      dramatically, and the electrophoresis run yields a short read length or fails
      completely.

PMID- 15852355
TI  - Electrokinetic properties of noncharged lipid nanocapsules: influence of the
      dipolar distribution at the interface.
AB  - Lipid nanocapsules (LNCs) containing poly(ethylene glycol) (PEG) were developed
      according to a phase inversion process without organic solvent. The distribution
      of PEG chains at the surface was determined due to electrokinetic properties, in
      order to correlate it with protein adsorption potentiality. In this aim,
      electrophoretic mobilities were measured as a function of ionic strength and pH,
      for particles differing by their size, dialysis effects, and the presence or not
      of lecithin in their shell. The study allowed the determination of the
      isoelectric point (pI) as well as the charge density (ZN) in relation with the
      dipolar distribution in the polyelectrolyte accessible layer (depth = 1/lambda),
      by using soft-particle electrophoresis analysis. These parameters pointed out
      that the PEG surface organization was dependent on the particle size. Moreover,
      this organization could be modified by dialyzing particles and/or by formulating
      them with or without lecithin. Lecithin was found to be present in the inner part
      of the polyelectrolyte layer and to play a role in the outer part
      disorganization. Dialyzing LNCs formulated with lecithin allowed to obtain stable
      and well-structured nanocapsules, ready to an in vivo use as drug delivery
      system.

PMID- 15852356
TI  - Epoetin-alpha during radiotherapy for stage III esophageal carcinoma.
AB  - BACKGROUND: It has been suggested that hemoglobin levels of 12-14 g/dL are
      optimal for tumor oxygenation, radiosensitivity, and prognosis. In this
      prospective study, the authors evaluated the effectiveness of epoetin-alpha to
      maintain hemoglobin levels at 12-14 g/dL during radiotherapy (RT) for patients
      with UICC Stage III esophageal carcinoma, and they examined the impact of
      erythropoetin on overall survival (OS), metastatic-free survival (MFS), and local
      control (LC). METHODS: Sixty patients who received RT between March, 2001 and
      September, 2004, were included in this prospective, nonrandomized study. Thirty
      patients received epoetin-alpha (150 IU/kg 3 times per week) during RT (Group A),
      and 30 patients did not receive epoetin-alpha (Group B). Epoetin-alpha was
      started at hemoglobin levels < 13 g/dL and was stopped at hemoglobin levels > or
      = 14 g/dL. Hemoglobin was measured before RT and once weekly during RT. RESULTS:
      Both patient groups were balanced for age, gender, performance status, tumor
      location/length, histology, grading, tumor classification, lymph node status,
      chemotherapy, treatment (45-50.4 grays [Gy] plus resection vs. 45.0-50.4 Gy vs.
      59.4-66.0 Gy), and hemoglobin level before RT. In 20 of 30 patients (67%) from
      Group A and in 3 of 30 patients (10%) from Group B, > or = 60% of hemoglobin
      levels during RT were 12-14 g/dL (P = 0.003). The median change in hemoglobin was
      + 0.4 g/dL per week in Group A and - 0.4 g/dL per week in Group B. LC was
      significantly better in Group A (66% vs. 38% at 1 year, respectively; P = 0.012),
      a trend was observed for OS (59% vs. 33%, respectively; P = 0.08), and MFS did
      not differ significantly (43% vs. 38%, respectively; P = 0.34). No epoetin-alpha
      related toxicity was observed. CONCLUSIONS: Epoetin-alpha was effective in
      maintaining the hemoglobin levels at 12-14 g/dL during RT. The application of
      epoetin-alpha significantly improved LC, and a trend was observed for OS.

PMID- 15852357
TI  - Risk factors for the development of second primary tumors among men after
      laryngeal and hypopharyngeal carcinoma.
AB  - BACKGROUND: Second primary tumors (SPT) constitute a major threat to the survival
      of patients with laryngeal carcinoma. However, to the authors' knowledge little
      is known regarding the risk factors for developing SPTs or about the strategy to
      be followed to avoid them. METHODS: Eight hundred seventy-six male patients with
      laryngeal/hypopharyngeal carcinoma enrolled in a population-based, case-control
      study in 5 centers from South Europe during 1979-1982 were followed up to
      ascertain the occurrence of SPTs. Standardized incidence ratios were calculated
      to estimate the risk of SPT occurring in the cohort. Cox proportional hazard
      models were fitted to estimate the hazard ratio for development of SPTs in
      relation to use of tobacco smoking, alcohol consumption, and dietary habits
      before the first primary tumor. RESULTS: One hundred forty-five patients
      developed an SPT with an annual average rate of 2.1%. An excess risk of
      developing an SPT of the tongue, mouth, esophagus, and lung was observed. No
      elevated risks of SPTs were observed in other organs. Alcohol consumption
      strongly increased the risk of developing an SPT of the upper aerodigestive tract
      (UADT). Heavy cumulative cigarette smoking increased the risk of developing a
      lung SPT. A protective effect of high intake of citrus fruit was noticed for SPT
      in the lung, whereas high butter intake was associated with an increased risk for
      SPT of the UADT. CONCLUSIONS: Continuous medical surveillance was essential in
      the UADT and lung to reduce the risk from an SPT after initial
      laryngeal/hypopahryngeal carcinoma. Alcohol consumption before the first primary
      tumor was a risk factor for SPT of the UADT. The study suggested a protective
      role of citrus fruits in the development of a lung SPT.

PMID- 15852358
TI  - Dedifferentiated parosteal osteosarcoma: the experience of the Rizzoli Institute.
AB  - BACKGROUND: Dedifferentiated parosteal osteosarcoma (DPOS) is a variant of
      osteosarcoma in which a high-grade sarcoma coexists with a conventional parosteal
      osteosarcoma (c-POS), either at presentation (synchronous type) or at the time of
      recurrence (metachronous type). Only approximately 60 patients have been reported
      in the literature. The objective of this study was to analyze the
      clinicopathologic and radiographic features of a relatively large number of
      patients with DPOS in an attempt to define further the histologic and biologic
      behavior of this rare entity. METHODS: In a series of 120 patients with parosteal
      osteosarcoma who were seen at the Rizzoli Institute from 1958 to 2000, the
      authors identified 29 patients who were diagnosed with DPOS. The authors reviewed
      the clinical and radiologic features, histologic sections, treatments, and
      outcomes in this group of patients with DPOS. RESULTS: Twelve patients were male,
      and 17 patients were female. The patients ranged in age from 15 years to 65 yrs
      (average, 36 years; median, 32 years). One tumor involved the scapula, one
      involved the ilium, and another involved the skull. All 26 of the other tumors
      were located in the long bones (14 in the femur, 5 in the humerus, 3 in the
      tibia, 3 in the fibula, and 1 in the ulna). In 18 patients, radiographic areas of
      lucency were seen within an otherwise sclerotic lesion. Histologically, the
      dedifferentiated component was high-grade osteoblastic osteosarcoma in 14
      patients, fibroblastic osteosarcoma in 10 patients, giant cell-rich osteosarcoma
      in 3 patients, and chondroblastic osteosarcoma in 2 patients. All tumors were
      Stage IIB, and invasion of the medullary canal was detected in 19 patients (65%).
      Twenty-eight patients underwent surgery, and 18 of those patients received
      chemotherapy (5 patients received neoadjuvant chemotherapy, and 13 patients
      received adjuvant). Nine patients were dead and 20 patients were alive (average
      follow-up, 107 months; range, from 3 months to 36 years) at the last follow-up.
      Of the nine patients who died, one patient received no treatment, five patients
      underwent surgery (with three patients achieving adequate margins) in combination
      with chemotherapy, and three patients underwent surgery only (with adequate
      margins achieved). Of the 20 patients who remained alive, 13 patients underwent
      surgery (with 10 patients achieving adequate margins) in combination with
      chemotherapy, whereas 7 patients underwent surgery only (all with adequate
      margins). Seven of the nine patients who died had widespread metastases. One
      patient died of causes unrelated to the tumor, and another patient died shortly
      after undergoing resection of a lesion in the skull. CONCLUSIONS:
      Dedifferentiation occurred in approximately 24% of patients with c-POS. The
      prognosis for patients with DPOS was better than the prognosis for patients with
      dedifferentiated central and dedifferentiated peripheral chondrosarcoma.

PMID- 15852359
TI  - Distribution according to histologic type and outcome by gender and age group in
      Taiwanese patients with lung carcinoma.
AB  - BACKGROUND: The results from previous studies suggested that the clinical
      characteristics and outcomes of patients with lung carcinoma vary between gender
      and age groups. The objective of the current study was to assess the trend in the
      evolution of the histologic types in Taiwan and to compare the outcomes of
      patients with lung carcinoma between different gender and age groups. METHODS:
      Patients with primary lung carcinoma were identified through the cancer registry
      system. Clinical records were reviewed and analyzed for age, gender, disease
      stage, histology, treatment modalities, and survival. A multivariate analysis
      using a Cox proportional hazards model was applied for gender, age (by decade),
      histologic type, disease stage, and treatment modality. RESULTS: Between 1991
      1999, 2714 patients with histologically or cytologically proven lung carcinoma
      were included. Adenocarcinoma was the major cell type of lung carcinoma (52.5%),
      with a significant trend toward an increase in adenocarcinoma during the study
      period. A significantly high percentage of adenocarcinoma was demonstrated in
      female patients (73.5%), who also had better survival compared with male patients
      (P = 0.002), especially in the group age 50-69 years. Patients age < 40 years
      also had a poor prognosis, which was worse compared with the prognosis for
      patients age 40-59 years. patients who had adenocarcinoma had a better survival
      rate compared with patients who had other histologic types (relative risk, 0.78;
      95% confidence interval, 0.69-0.87). CONCLUSIONS: Adenocarcinoma was predominant
      in female patients and emerged as a greater problem than other histologic types
      in Taiwan, potentially raising the importance of studies regarding the benefit of
      population diversity in new antitumor therapies, such as gefitinib. Female
      patients with lung carcinoma had a better prognosis than male patients in the
      group age 50-69 years, warranting further studies on potential prognostic factors
      associated with middle age, such as hormone status.

PMID- 15852360
TI  - Women age < or = 35 years with primary breast carcinoma: disease features at
      presentation.
AB  - BACKGROUND: The purpose of the current study was to describe a population of
      young patients with breast carcinoma, their characteristics at the time of
      diagnosis, and the association of these characteristics with disease recurrence
      and survival. METHODS: Four hundred fifty-two women age < or = 35 years with
      breast carcinoma were registered at The University of Texas M. D. Anderson Cancer
      Center (Houston, TX) between 1990 and 2002. The relation between
      clinicopathologic factors and disease recurrence-free survival (RFS) and overall
      survival (OS) was assessed. Cox regression analysis was used to identify
      independent survival predictors. RESULTS: The median age of the patients was 32
      years. Most of the patients were white, and 20% were obese. Approximately 50%
      reported oral contraceptive use, 34% reported a family history of breast
      carcinoma, and 5% reported a family history of ovarian carcinoma. Sixty-nine
      percent of tumors were nuclear Grade 3 (using the modified Black's nuclear
      grading system), 52% had positive estrogen receptors, and 48% had positive
      progesterone receptors. HER-2/neu status was available in 60% of tumor specimens
      and 34% were HER-2/neu positive. The median follow-up was 36 months. There were
      185 disease recurrences and 84 deaths. RFS was significantly shorter in patients
      who reported a family history of ovarian carcinoma (P < 0.0001) and in those who
      had hormone receptor-negative tumor specimens (P = 0.001). OS was significantly
      shorter in patients who reported a family history of ovarian carcinoma (P =
      0.001), those who had hormone receptor-negative tumor specimens (P < 0.0001), or
      those with > nuclear Grade 3 tumor specimens (P = 0.005). CONCLUSIONS: This young
      population with breast carcinoma was found to have more aggressive biologic
      features. Hormone receptor negativity and a family history of ovarian carcinoma
      were associated with shorter RFS and OS.

PMID- 15852362
TI  - The risk of developing second cancers among survivors of childhood soft tissue
      sarcoma.
AB  - BACKGROUND: Previous studies have shown that children who are treated for soft
      tissue sarcoma (STS) are at increased risk for developing second cancers.
      However, the risk for specific cancer sites and variations in risk by treatment
      and STS histology remain unclear. METHODS: The study evaluated 1499 children (age
      < 18 years) who survived for > or = 1 year after they were diagnosed with STS and
      who were reported to the Surveillance, Epidemiology, and End Results (SEER)
      population-based cancer registries from 1973 to 2000. RESULTS: Twenty-seven
      children developed 28 subsequent primary malignancies, compared with 4.5 expected
      malignancies based on general population rates (observed-to-expected [O/E] ratio
      = 6.3 (95% confidence interval [95% CI], 4.2-9.1). The risk of developing a
      subsequent malignancy was increased among children with rhabdomyosarcoma
      (observed = 11 malignancies; O/E ratio = 7.7), fibromatous neoplasms (observed =
      9 malignancies; O/E ratio = 5.8), and other specified STS (observed = 7
      malignancies; O/E ratio = 6.5). Initial therapy with radiation and
      chemotherapeutic agents was associated with a significantly higher risk of second
      malignancies compared with surgery alone (O/E ratio = 15.2 vs. 1.4; P < 0.0001).
      Elevated risks were observed for acute myeloid leukemia, cutaneous melanoma,
      female breast cancer, and sarcomas of the bone and soft tissue, with generally
      higher risks among patients who initially received combined modality therapy.
      Excess cancers of the oral cavity were prominent among long-term survivors. For
      several children, the pattern of multiple malignancies was consistent with a
      genetic syndrome, particularly neurofibromatosis type 1 and Li-Fraumeni syndrome.
      CONCLUSIONS: The risk of second malignancies was increased for all histologic
      types of childhood STS and was particularly high among patients who received
      combined modality therapy.

PMID- 15852361
TI  - Undetectable prostate specific antigen at 6-12 months: a new marker for early
      success in hormonally treated patients after prostate brachytherapy.
AB  - BACKGROUND: The concept of a prostate-specific antigen (PSA) "nadir" has been
      used as a predictive marker for treatment success in patients treated with
      radiotherapy for localized prostate carcinoma. However, this approach is not
      applicable in patients who are concomitantly treated with short-term hormonal
      therapies. To address this, the authors sought to develop a new predictive marker
      in such patients after prostate brachytherapy (BT). METHODS: Between March 1997
      and November 2002, 194 men with clinical Stage T1A-T3N0M0 prostate carcinoma
      (according to the 1992 International Union Against Cancer/American Joint
      Committee on Cancer TNM classification system) were treated with interstitial
      palladium (103Pd3) BT and androgen ablation therapy with or without external beam
      radiotherapy (EBRT). Based on tumor characteristics, 127 patients received an
      antiandrogen, finasteride, and BT whereas 67 received an antiandrogen,
      leuprolide, and EBRT followed by a BT boost. Hormonal therapy was initiated 2-3
      months before any radiotherapy for a total duration of 8-9 months. Follow-up
      included physical examination and determining the PSA level at 3-month intervals.
      Postoperative serum testosterone was evaluated in preoperatively potent patients
      with erectile dysfunction > 6 months after therapy. A PSA level < or = 0.06 ng/mL
      or < or = 0.20 ng/mL detected during a 6-12-month window after the implant were
      evaluated as predictors of biochemically disease-free survival (DFS), defined as
      the time to a PSA level > or = 1.0 ng/mL. RESULTS: Of the 194 patients, 163 were
      available for analysis. The median length of follow-up was 48 months. In those
      patients with a PSA level < or = 0.20 ng/mL at 6-12 months, the DFS at 48 months
      after the implant was 96% (95% confidence interval [95% CI], 91-99%) compared
      with the remainder of the patients, whose DFS decreased to 80% (95% CI, 65-89%)
      (P < 0.001). When a PSA level < or = 0.06 ng/mL was used as an indicator, the 48
      month DFS was 99% (95% CI, 91-100%) compared with that for patients with a PSA
      level > 0.06 ng/mL, in whom the DFS was 85% (95% CI, 74-92%) (P = 0.004).
      Furthermore, because testosterone levels may occasionally remain low after the
      cessation of luteinizing hormone-releasing hormone agonist therapy and result in
      erectile dysfunction and an artificially low PSA level, the authors reviewed the
      serum testosterone levels in 23 patients who were so treated and were
      experiencing erectile dysfunction. None had PSA values below the lower limit of
      normal. CONCLUSIONS: A PSA level < or = 0.20 ng/mL or < or = 0.06 ng/mL measured
      at 6-12 months after BT appears to be a useful predictive marker for detecting
      early success in patients with prostate carcinoma who are treated with
      neoadjuvant androgen ablation and BT. These markers may be used to identify those
      patients who are at an increased risk of biochemical failure and may be useful in
      stratifying patients for closer follow-up, long-term adjuvant therapies, or
      clinical trials. A longer follow-up period will be needed to verify whether these
      are predictive of long-term cancer control.

PMID- 15852363
TI  - Pallidal stimulation reduces treatment-induced dyskinesias in "minimal-change"
      multiple system atrophy.
AB  - Deep brain stimulation therapy is increasingly gaining acceptance in the
      management of levodopa-induced dyskinesia and fluctuations in idiopathic
      Parkinson's disease. It is generally not recommended for the other forms of
      parkinsonism such as progressive supranuclear palsy or multiple system atrophy
      where the response to levodopa is usually poor and disease progression more
      rapid, making any benefit short-lived. Here, we present an autopsy-confirmed case
      of "minimal-change" multiple system atrophy in whom pallidal stimulation surgery
      was effective in abolishing severe levodopa-induced dyskinesia.

PMID- 15852364
TI  - Apolipoprotein E epsilon4 and catechol-O-methyltransferase alleles in autopsy
      proven Parkinson's disease: relationship to dementia and hallucinations.
AB  - We determined whether apolipoprotein E epsilon4 (ApoE4) or catechol-O
      methyltransferase (COMT) genotypes were associated with dementia, hallucinations,
      Alzheimer's disease pathological findings (AP), or cortical Lewy bodies (CLBs) in
      autopsy-confirmed cases of Parkinson's disease (PD). Outcomes were obtained from
      medical records. Pathology reports identified AP and CLBs. Brain tissue was
      genotyped. A total of 47 subjects (33 men, 14 women) had PD onset at 62.4 +/- 8.7
      years of age and died at 77.8 +/- 5.6 years of age. Demented and hallucinating
      patients did not differ in age at onset (AO) of PD or age at death, or the
      proportion ApoE4+, AP+, or CLB+ compared to nondemented patients or non
      hallucinating patients. ApoE4 and COMT (low metabolizer [LH], intermediate
      metabolizer [HL], or high metabolizer [HH]) did not influence AO, death, or
      dementia- or hallucination-free survival, based on age or duration of treatment.
      All seven subjects with AP were demented and had hallucinations. CLBs were
      associated with dementia but not hallucinations. In Cox regression models
      adjusting for AO and duration of treatment, increased risk of dementia was
      associated with male sex but not significantly with ApoE4; inclusion of AP in the
      model did not affect the results; COMT was not a risk factor for dementia.
      Psychosis risk was not associated with ApoE4, COMT, or sex. The observation that
      males have increased dementia risk and the trend for ApoE4 requires confirmation
      in larger prospective autopsy studies.

PMID- 15852365
TI  - A new mutation (Thr106Ile) of the GTP cyclohydrolase 1 gene associated with DYT5
      dystonia (Segawa disease).

PMID- 15852366
TI  - Mutation of the Parkin gene in a Persian family: clinical progression over a 40
      year period.
AB  - We report on an Israeli family originating from Iran in which 4 of 7 brothers
      born from a consanguineous marriage had juvenile Parkinsonism. Linkage analysis
      of markers covering the autosomal recessive juvenile Parkinsonism (AR-JP, PARK2,
      Parkin gene, OMIM #602544) gene resulted in a maximal logarithm of odds score of
      2.18. A homozygous deletion that expanded from exon 4 to exon 6 was identified in
      all the patients. Significant clinical heterogeneity was present between
      siblings.

PMID- 15852367
TI  - Can chronic subthalamic nucleus stimulation induce de novo tremor in Parkinson's
      disease?
AB  - Subthalamic nucleus stimulation dramatically improves parkinsonian symptoms,
      notably the tremor. The occurrence of a tremor in the first 6 months after the
      surgical procedure in patients without tremor preoperatively is much less common.
      We report on the cases of 3 patients who developed such modification of their
      parkinsonian symptomatology. Physiopathological hypotheses are discussed.

PMID- 15852368
TI  - Cross-sectional survey of Parkinson's disease and parkinsonism in a rural area of
      the United Kingdom.
AB  - The objective of this study was to estimate the crude and standardized age/sex
      adjusted prevalence rates of parkinsonism and Parkinson's disease (PD) in a rural
      area of North Wales. Cases of PD and parkinsonism in a geographically defined
      rural area of North Wales were ascertained from the prescription of
      antiparkinsonian medication in primary care, hospital records, attendance at
      general medical outpatient clinics and at a specialist movement disorder clinic.
      In this population, the crude prevalence of clinically probable/possible PD was
      144 per 1000,000 (95% confidence interval [CI], 120-173) and for parkinsonism 169
      per 100,000 (95% CI, 143-201). When adjusted to the UK population, the prevalence
      for clinically probable PD was 105 per 100,000 (95% CI, 85-124) and for
      parkinsonism 122 per 100,000 (95% CI, 102-143). Age- and sex-adjusted
      standardized rates indicate that regional variations in PD and parkinsonism may
      exist in the United Kingdom. There are several possible reasons for this,
      although methodological differences between studies may be the most likely
      explanations for the present findings.

PMID- 15852369
TI  - Virus-delivered small RNA silencing sustains strength in amyotrophic lateral
      sclerosis.
AB  - Mutations in superoxide dismutase cause a subset of familial amyotrophic lateral
      sclerosis and provoke progressive paralysis when expressed in mice. After
      retrograde transport to the spinal cord following injection into muscles, an
      adeno-associated virus carrying a gene that encodes a small interfering RNA was
      shown to target superoxide dismutase messenger RNA for degradation. The
      corresponding decrease in mutant superoxide dismutase in spinal motor neurons
      preserved grip strength. This finding provides proof of principle for the
      selective reduction of any neuronal protein and supports intramuscular injections
      of a small interfering RNA-encoding virus as a viable therapy for this type of
      familial amyotrophic lateral sclerosis.

PMID- 15852370
TI  - Electrophysiologic transition from physiologic tremor to essential tremor.
AB  - We electrophysiologically examined the transition from physiologic tremor to
      essential tremor in people at risk for familial essential tremor. Two healthy
      people from different families with hereditary essential tremor were studied on
      multiple occasions. A 23-year-old man was studied in 1995, 1997, and 2004, and a
      44-year-old woman was studied in 1993, 1995, 1997, and 2003. Hand acceleration
      and forearm electromyographic readings were measured with and without 300-g
      loading to determine the characteristic frequency-invariant motor unit
      entrainment of essential tremor. Clinically and electrophysiologically, the man
      and woman had normal tremor until the last examination, when both exhibited a
      fine tremulousness in the outstretched hands and frequency-invariant motor unit
      entrainment at 7.5 and 6.5 Hz, respectively. At no time did either patient
      exhibit a prominent 8-12 Hz component of physiologic tremor. Essential tremor in
      young adults may begin at frequencies less than 8-12 Hz, and this
      electrophysiologic abnormality is detectable when clinical examinations reveal
      only questionably abnormal tremor. More young adults at risk for essential tremor
      must be studied to determine whether initial frequencies less than 8 Hz are the
      rule or the exception. Nevertheless, the data from our 2 patients demonstrate
      that a prominent 8-12 Hz component of physiologic tremor does not always precede
      the development of essential tremor; therefore, the origins of essential tremor
      and the 8-12 Hz component of physiologic tremor may be different.

PMID- 15852371
TI  - Clinical features of LRRK2-associated Parkinson's disease in central Norway.
AB  - Several pathogenic mutations in the leucine-rich repeat kinase 2 (LRRK2; PARK8)
      gene recently have been identified in familial and sporadic parkinsonism. We
      screened 435 Norwegian patients diagnosed with Parkinson's disease and 519
      control subjects for the presence of 7 LRRK2 mutations. Nine patients from seven
      families were found to be heterozygote carriers of the LRRK2 6055G>A (G2019S)
      mutation. Twelve of 28 first-degree relatives also carried the mutation, but only
      1 had Parkinson's disease. The clinical features included asymmetric resting
      tremor, bradykinesia, and rigidity with a good response to levodopa and could not
      be distinguished from idiopathic Parkinson's disease.

PMID- 15852372
TI  - Overlap of pathology in paralytic rabies and axonal Guillain-Barre syndrome.
AB  - We describe clinical and pathological features of a case of paralytic rabies with
      acute axonal neuropathy that closely resembled axonal Guillain-Barre syndrome.
      This case emphasizes that there is overlap of both clinical and pathological
      features in paralytic rabies and axonal Guillain-Barre syndrome. These findings
      raise the possibility that infectious and autoimmune etiologies can lead to
      similar morphological changes in the nerves.

PMID- 15852373
TI  - Aerobic training in patients with myotonic dystrophy type 1.
AB  - The effect of 12 weeks of aerobic training on a cycle ergometer was studied in 12
      patients with myotonic dystrophy. Efficacy was evaluated by cycle testing and
      muscle morphology before and after training. Patients increased their maximal
      oxygen uptake by 14%, the maximal workload by 11%, muscle fiber diameter
      increased significantly, and creatine kinase did not increase with training. The
      study indicates that aerobic training is safe and can improve fitness effectively
      in patients with myotonic dystrophy.

PMID- 15852374
TI  - Neuroprotection by the PGE2 EP2 receptor in permanent focal cerebral ischemia.
AB  - Recent studies suggest a neuroprotective function of the PGE2 EP2 receptor in
      excitotoxic neuronal injury. The function of the EP2 receptor was examined at
      time points after excitotoxicity in an organotypic hippocampal model of N-methyl
      D-aspartate (NMDA) challenge and in a permanent model of focal forebrain
      ischemia. Activation of EP2 led to significant neuroprotection in hippocampal
      slices up to 3 hours after a toxic NMDA stimulus. Genetic deletion of EP2
      resulted in a marked increase in stroke volume in the permanent middle cerebral
      artery occlusion model. These findings support further investigation into
      therapeutic strategies targeting the EP2 receptor in stroke.

PMID- 15852375
TI  - Effects of Cav3.2 channel mutations linked to idiopathic generalized epilepsy.
AB  - Heron and colleagues (Ann Neurol 2004;55:595-596) identified three missense
      mutations in the Cav3.2 T-type calcium channel gene (CACNA1H) in patients with
      idiopathic generalized epilepsy. None of the variants were associated with a
      specific epilepsy phenotype and were not found in patients with juvenile absence
      epilepsy or childhood absence epilepsy. Here, we introduced and functionally
      characterized these three mutations using transiently expressed human Cav3.2
      channels. Two of the mutations exhibited functional changes that are consistent
      with increased channel function. Taken together, these findings along with
      previous reports, strongly implicate CACNA1H as a susceptibility gene in complex
      idiopathic generalized epilepsy.

PMID- 15852376
TI  - Severe neuropathy with leaky connexin32 hemichannels.
AB  - X-linked Charcot-Marie-Tooth disease is one of a set of diseases caused by
      mutations in gap junction proteins called connexins. We identified a connexin32
      missense mutation (F235C) in a girl with unusually severe neuropathy. The
      localization and trafficking of the mutant protein in cell culture was normal,
      but electrophysiological studies showed that the mutation caused abnormal
      hemichannel opening, with excessive permeability of the plasma membrane and
      decreased cell survival. Abnormal leakiness of connexin hemichannels is likely a
      mechanism of cellular toxicity in this and perhaps other diseases caused by
      connexin mutations.

PMID- 15852377
TI  - Genetic linkage of autosomal dominant progressive supranuclear palsy to 1q31.1.
AB  - Progressive supranuclear palsy (PSP) is a disorder of unknown pathogenesis.
      Familial clusters of PSP have been reported related to mutations of protein tau.
      We report the linkage of a large Spanish family with typical autosomal dominant
      PSP to a new locus in chromosome 1. Four members of this family had typical PSP,
      confirmed by neuropathology in one case. At least five ancestors had similar
      disease. Other members of the family have incomplete phenotypes. The power of the
      linkage analysis was increased by detecting presymptomatic individuals with 18F
      fluoro-dopa and 18F-deoxyglucose positron emission tomography. We screened the
      human genome with 340 polymorphic markers and we enriched the areas of interest
      with additional markers. The disease status was defined according to the clinical
      and positron emission tomography data. We excluded linkage to the tau gene in
      chromosome 17. PSP was linked, in this family, to one area of 3.4 cM in
      chromosome 1q31.1, with a maximal multipoint < OD score of +3.53. This area
      contains at least three genes, whose relevance in PSP is unknown. We expect to
      further define the gene responsible for PSP, which could help to understand the
      pathogenesis of this disease and to design effective treatment.

PMID- 15852378
TI  - Protective effects of ginseng components in a rodent model of neurodegeneration.
AB  - To test the proposed neuroprotective activity of whole ginseng extract and its
      components, we used 3-nitropropionic acid (3-NP), an inhibitor of succinate
      dehydrogenase, to produce neurodegeneration. Treatment with 3-nitropropionic acid
      (90 mg/kg) over a 5-day period resulted in severe impairment of movement and loss
      of neurons in the striatum. Pretreatment with a preparation from the whole root
      of American ginseng had no protective effects. Pretreatment with a preparation of
      ground leaves and stems, which contains greater levels of ginsenosides than
      ground root, improved the behavioral score and reduced the volume of the striatal
      lesion. A partial purification of American ginseng was performed to concentrate
      the putative protective components: Rb1, Rb3, and Rd (termed Rb extract).
      Pretreatment with the Rb extract significantly reduced the 3-nitropropionic acid
      induced motor impairment and cell loss in the striatum, and it completely
      prevented any mortality. Significant effects on motor function, mortality, and
      the striatal lesion volume also were measured in animals pretreated with the
      individual ginsenosides, Rb1, Rb3, or Rd. The results demonstrate that some of
      the ginsenosides have neuroprotective activity, and that a partial purification
      of whole ginseng to concentrate the neuroprotective components may have utility
      as a neuroprotective agent.

PMID- 15852379
TI  - Attentional modulation of perceptual grouping in human visual cortex: functional
      MRI studies.
AB  - When presented with a complex visual scene, our visual system has to organize the
      discrete entities present into useful perceptual units. The current work
      investigated the neural substrates of perceptual grouping defined by Gestalt laws
      of proximity and similarity of shape, and whether the neural substrates
      underlying perceptual grouping are modulated by task relevance and spatial
      attention. In visual discrimination tasks, subjects identified the orientations
      of perceptual groups formed by proximity or similarity of local elements or
      alternatively identified colors of either dots around the grouped stimuli or the
      fixation cross. Using functional magnetic resonance imaging (fMRI), we identified
      that the calcarine cortex was involved in proximity grouping but not in the
      grouping process defined by similarity of shape. Moreover, we showed evidence
      that the neural correlates of proximity grouping in the calcarine cortex were
      weakened when the elements were of low task relevance and fell outside an
      attended area of field. The findings reveal the neural basis for basic grouping
      operations, as well as illustrating how attention and proximity grouping interact
      in human visual cortex.

PMID- 15852380
TI  - Adaptive cortical plasticity in higher visual areas after acute optic neuritis.
AB  - The ability to distinguish adaptive cortical reorganization may help to target
      future therapeutic strategies after neurological insult. We investigated cortical
      plasticity by prospectively applying visual functional magnetic resonance imaging
      (fMRI) and optic nerve MRI to 20 patients with acute optic neuritis at baseline,
      1, 3, 6, and 12 months. We performed three types of correlation analyses to
      investigate the relationships between fMRI activity, clinical function, and optic
      nerve structure. The first analysis directly correlated the fMRI response to
      clinical function or optic nerve structure and found dynamic relations especially
      within the first 3 months. The second analysis used a novel technique that
      modeled the fMRI response and optic nerve structure together with clinical
      function, to determine the contribution fMRI made to clinical function after
      accounting for structural factors. Significant effects were found at baseline
      only, within the right peristriate cortex, and bilaterally in the lateral
      occipital complexes, which are normally involved in higher order visual
      processing. The third analysis investigated the relation between the modeled
      visual recovery rate and fMRI response but found no significant effects. The key
      findings of this study are from the second analysis and suggest a genuine
      adaptive role for cortical reorganization within extrastriate visual areas early
      after optic neuritis.

PMID- 15852381
TI  - Preservation of limbic and paralimbic structures in aging.
AB  - Patterns of gray matter (GM) loss were measured in 223 healthy subjects spanning
      eight decades. We observed significant clusters of accelerated loss in focal
      regions of the frontal and parietal cortices, including the dorsolateral frontal
      cortex, pre- and postcentral gyrus, and the inferior and superior parietal lobes.
      The rate of loss in these clusters was approximately twice that of the global
      average. By contrast, clusters of significant GM preservation were found in
      limbic and paralimbic structures, including the amygdala, hippocampus, thalamus,
      and the cingulate gyrus. In these clusters, GM loss was attenuated significantly
      relative to the global rate. The preservation of these structures is consistent
      with the functional importance of the thalamo-limbic circuits in sensory
      integration, arousal, emotion, and memory, and lends credence to the idea that
      later-maturing cortical regions are more vulnerable to age-related morphologic
      changes. Moreover, the limbic findings act as a frame of reference to explore
      further the effects of stress and learning on these structures in an evidence
      based manner across age.

PMID- 15852382
TI  - Within-subject reproducibility of category-specific visual activation with
      functional MRI.
AB  - We used functional magnetic resonance imaging (fMRI) to investigate within
      subject reproducibility of activation in higher level, category-specific visual
      areas to validate the functional localization approach widely used for these
      areas. The brain areas investigated included the extrastriate body area (EBA),
      which responds selectively to human bodies, the fusiform face area (FFA) and the
      occipital face area (OFA), which respond selectively to faces, and the
      parahippocampal place area (PPA), which responds selectively to places and
      scenes. All six subjects showed significant bilateral activation in the four
      areas. Reproducibility was very high for all areas, both within a scanning
      session and between scanning sessions separated by 3 weeks. Within sessions, the
      mean distance between peak voxels of the same area localized by using different
      functional runs was 1.5 mm. The mean distance between peak voxels of areas
      localized in different sessions was 2.9 mm. Functional reproducibility, as
      expressed by the stability of T-values across sessions, was high for both within
      session and between-session comparisons. We conclude that within subjects, high
      level category-specific visual areas can be localized robustly across scanning
      sessions.

PMID- 15852383
TI  - Asymmetry analysis of deformable hippocampal model using the principal component
      in schizophrenia.
AB  - The hippocampus is thought to play an important role in learning and memory
      processing, and impairments in memory, attention, and decision making are found
      commonly in schizophrenia. Although many studies have reported decreases in
      hippocampal volume in the left hemisphere in schizophrenia, regionally specific
      hippocampal volume loss has not been revealed consistently using volume analysis.
      Recently, many studies have analyzed shape asymmetry using 3-D models; however,
      inconsistent results have been reported, mainly due to methodologic differences.
      We therefore used an active, flexible, deformable shape model for surface
      parameterization, and compared shape asymmetry based on principal component
      analysis (PCA) in the hippocampi of schizophrenic patients with those of the
      normal controls. Although the overall pattern of the statistical results did not
      change according to the number of principal components, the reconstructed results
      based on six major components were much more distinguishable. Although the left
      hemispheric hippocampal volume was larger than the right hemispheric was in this
      study, the difference was not significant. In shape asymmetry analysis, the right
      hemisphere hippocampus was bilaterally larger than the left hemisphere
      hippocampus was in the head of the superior CA1 and smaller in the tail and head
      of the inferior CA1. The asymmetry in the schizophrenia group was statistically
      smaller than that in the control group through reduction of the left hemisphere
      hippocampus volume.

PMID- 15852384
TI  - Tactile discrimination of grating orientation: fMRI activation patterns.
AB  - Grating orientation discrimination is employed widely to test tactile spatial
      acuity. We used functional magnetic resonance imaging (fMRI) to investigate the
      neural circuitry underlying performance of this task. Two studies were carried
      out. In the first study, an extensive set of parietal and frontal cortical areas
      was activated during covert task performance, relative to a rest baseline. The
      active regions included the postcentral sulcus bilaterally and foci in the left
      parietal operculum, left anterior intraparietal sulcus, and bilateral premotor
      and prefrontal cortex. The second study examined selective recruitment of
      cortical areas during discrimination of grating orientation (a task with a
      macrospatial component) compared to discrimination of grating spacing (a purely
      microspatial task). The foci activated on this contrast were in the left anterior
      intraparietal sulcus, right postcentral sulcus and gyrus, left parieto-occipital
      cortex, bilateral frontal eye fields, and bilateral ventral premotor cortex.
      These findings not only confirm and extend previous studies of the neural
      processing underlying grating orientation discrimination, but also demonstrate
      that a distributed network of putatively multisensory areas is involved.

PMID- 15852385
TI  - Effects of long-term practice and task complexity in musicians and nonmusicians
      performing simple and complex motor tasks: implications for cortical motor
      organization.
AB  - Motor practice induces plastic changes within the cortical motor system. Whereas
      rapidly evolving changes of cortical motor representations were the subject of a
      number of recent studies, effects of long-term practice on the motor system are
      so far poorly understood. In the present study pianists and nonmusicians were
      investigated using functional magnetic resonance imaging. Both groups performed
      simple and complex movement sequences on a keyboard with the right hand, the
      tasks requiring different levels of ordinal complexity. The aim of this study was
      to characterize motor representations related to sequence complexity and to long
      term motor practice. In nonmusicians, complex motor sequences showed higher fMRI
      activations of the presupplementary motor area (pre-SMA) and the rostral part of
      the dorsal premotor cortex (PMd) compared to simple motor sequences, whereas
      musicians showed no differential activations. These results may reflect the
      higher level of visuomotor integration required in the complex task in
      nonmusicians, whereas in musicians this rostral premotor network was employed
      during both tasks. Comparison of subject groups revealed increased activation of
      a more caudal premotor network in nonmusicians comprising the caudal part of the
      PMd and the supplementary motor area. This supports recent results suggesting a
      specialization within PMd. Furthermore, we conclude that plasticity due to long
      term practice mainly occurs in caudal motor areas directly related to motor
      execution. The slowly evolving changes in M1 during motor skill learning may
      extend to adjacent areas, leading to more effective motor representations in
      pianists.

PMID- 15852386
TI  - Visualization of thalamic nuclei on high resolution, multi-averaged T1 and T2
      maps acquired at 1.5 T.
AB  - The ability to differentiate noninvasively between the primary nuclear divisions
      of the thalamus has immediate clinical applicability for surgical planning and
      guidance of functional stereotactic procedures. Comparison of prior qualitative
      magnetic resonance imaging (MRI) studies carried out at field strengths of 1.5
      and 4 Tesla have revealed contrast within the thalamus that varies with field
      strength, suggesting possible differences in the inherent T1 and T2 relaxation
      times of the constituent nuclei. We investigate this hypothesis through
      acquisition of high-resolution, multi-averaged deep-brain T1 and T2 maps of a
      healthy volunteer. Fourteen nuclei were identified using their center-of-mass
      coordinates (in Talairach space) and average T1 and T2 values obtained from
      regions of interest placed within each. Results from this analysis revealed
      significant differences in T1 and T2 between the nuclei with a T1 range from 700
      to 1,400 ms and a T2 range from 89 to 122 ms, allowing visual discrimination
      between the major nuclei groups. Furthermore, the high-resolution images showed
      distinct borders of T1 and T2 hypointensity surrounding each nucleus, revealing
      structure not reported previously. These results confirm our hypothesis and
      demonstrate the potential high-resolution quantitative imaging for nucleus
      visualization and surgical planning.

PMID- 15852388
TI  - Function of striatum beyond inhibition and execution of motor responses.
AB  - We used functional magnetic resonance imaging (fMRI) to study the role of the
      striatum in inhibitory motor control. Subjects had to refrain from responding to
      designated items (STOP trials) within a similar series of motor stimuli. Striatal
      activation was increased significantly compared to that when responding to all
      targets within a series of motor stimuli, indicating that the striatum is more
      active when inhibitory motor control over responses is required. The likelihood
      of a STOP trial was varied parametrically by varying the number of GO trials
      before a STOP trial. We could thus measure the effect of expecting a STOP trial
      on the fMRI response in the striatum. We show for the first time in humans that
      the striatum becomes more active when the likelihood of inhibiting a planned
      motor response increases. Our findings suggest that the striatum is critically
      involved in inhibitory motor control, most likely by controlling the execution of
      planned motor responses.

PMID- 15852389
TI  - High endogenous cannabinoid levels in the cerebrospinal fluid of untreated
      Parkinson's disease patients.

PMID- 15852390
TI  - Serum lipids and hippocampal volume: the link to Alzheimer's disease?

PMID- 15852391
TI  - Torsin A haplotype predisposes to idiopathic dystonia.
AB  - Previous work has suggested that in many neurological diseases genetic
      variability in the loci predisposing subjects to autosomal dominant disease
      contributes to the risk of sporadic disease. Here, using a population-based
      sample of dystonia cases, we show an association with the torsin A haplotype and
      sporadic idiopathic dystonia.

PMID- 15852392
TI  - Very late onset in ataxia oculomotor apraxia type I.

PMID- 15852393
TI  - Pallidal stimulation improves pantothenate kinase-associated neurodegeneration.
AB  - Pantothenate kinase-associated neurodegeneration (PKAN) causes a progressive
      generalized dystonia which remains pharmacologically intractable. We performed
      bilateral internal globus pallidus stimulation in six patients with genetically
      confirmed PKAN who obtained a major and long-lasting improvement of their painful
      spasms, dystonia, and functional autonomy. This study shows the benefits of
      pallidal DBS for the dystonia of PKAN patients.

PMID- 15852394
TI  - Acetylcholinesterase inhibitors reduce brain and blood interleukin-1beta
      production.
AB  - Overproduction of interleukin-1 within the brain is associated with Alzheimer's
      disease and other neurological conditions. We report that peripheral
      administration of the acetylcholinesterase inhibitors tacrine, rivastigmine,
      neostigmine, or EN101 (an antisense oligonucleotide directed at
      acetylcholinesterase messenger RNA) to mice significantly attenuated the
      production of interleukin-1beta in the hippocampus and blood, concomitantly with
      the reduction in acetylcholinesterase activity. These findings demonstrate that
      cholinergic enhancement produces central and peripheral antiinflammatory effects
      and suggest a novel therapeutic mechanism for acetylcholinesterase inhibitors.

PMID- 15852395
TI  - Cerebrospinal fluid profile in frontotemporal dementia and Alzheimer's disease.
AB  - We assessed cerebrospinal fluid (CSF) levels of tau and other biomarkers of
      neurodegenerative disease. CSF tau levels vary widely in reports of
      frontotemporal dementia (FTD). CSF samples were assayed for tau, amyloid beta1-42
      (A1-42), and the isoprostane 8,12-iso-iPF2a-VI (iP) prospectively in 64 patients
      with FTD, retrospectively in 26 autopsied cases with FTD or Alzheimer's disease
      (AD), and in 13 healthy seniors. To validate our observations in vivo, we
      correlated CSF tau levels with cortical atrophy in 17 FTD patients using voxel
      based morphometry analyses of high-resolution magnetic resonance imaging. CSF
      levels of tau, Abeta1-42, and iP differed significantly in FTD compared with AD.
      Individual patient analyses showed that 34% of FD patients had significantly low
      levels of CSF tau, although this was never seen in AD. A discriminant analysis
      based on CSF levels of tau, Abeta1-42, and iP was able to classify 88.5% of these
      patients in a manner that corresponds to their clinical or autopsy diagnosis.
      Magnetic resonance imaging studies showed that CSF tau levels correlate
      significantly with right frontal and left temporal cortical atrophy, brain
      regions known to be atrophic in patients with autopsy-proved FTD. We conclude
      that CSF tau levels are significantly reduced in many patients with FTD.

PMID- 15852396
TI  - Spastic paraplegia, optic atrophy, and neuropathy is linked to chromosome 11q13.
AB  - We report an autosomal recessive neurodegenerative disorder in 25 white members
      from a large inbred Brazilian family, 22 of whom were evaluated clinically. This
      condition is characterized by (1) subnormal vision secondary to apparently
      nonprogressive congenital optic atrophy; (2) onset of progressive spastic
      paraplegia in infancy; (3) onset of progressive motor and sensory axonal
      neuropathy in late childhood/early adolescence; (4) dysarthria starting in the
      third decade of life; (5) exacerbated acoustic startle response; and (6)
      progressive joint contractures and spine deformities. Motor handicap was severe,
      and all patients were wheelchair bound after 15 years old. We performed a genome
      wide screen including 25 affected individuals and 49 of their unaffected
      relatives. Linkage was detected at 11q13 region with a maximum logarithm of odds
      score of +14.43, obtained with marker D11S1883. The candidate region, which lies
      between D11S1908 and D11S1889, encompasses approximately 4.8Mb and has more than
      100 genes and expressed sequences. We propose the acronym SPOAN (spastic
      paraplegia, optic atrophy, and neuropathy) for this complex syndrome.

PMID- 15852397
TI  - Natural history of denervation in SMA: relation to age, SMN2 copy number, and
      function.
AB  - Denervation was assessed in 89 spinal muscular atrophy (SMA) 1, 2, and 3 subjects
      via motor unit number estimation (MUNE) and maximum compound motor action
      potential amplitude (CMAP) studies, and results correlated with SMN2 copy, age,
      and function. MUNE and maximum CMAP values were distinct among SMA subtypes (p <
      0.05). Changes in MUNE and maximum CMAP values over time were dependent on age,
      SMA type, and SMN2 copy number. SMN2 copy number less than 3 correlated with
      lower MUNE and maximum CMAP values (p < 0.0001) and worse functional outcomes. As
      SMN2 copy number increases, so does functional status (p < 0.0001). Change in
      MUNE longitudinally over the time intervals examined in this study was not
      statistically significant for any SMA cohort. However, a decline in maximum CMAP
      over time was apparent in SMA2 subjects (p = 0.049). Age-dependent decline in
      MUNE and maximum CMAP was apparent in both SMA 1 (p < 0.0001) and SMA 2 (p <
      0.0001) subjects, with age as an independent factor regardless of type. Maximum
      CMAP at the time of the initial assessment was most predictive of functional
      outcome (p < 0.0001). Prospective longitudinal studies in four prenatally
      diagnosed infants demonstrated significant progressive denervation in association
      with symptomatic onset or functional decline. These data highlight the potential
      value of such measures in increasing our understanding of pathophysiological
      factors involved in denervation in SMA.

PMID- 15852398
TI  - Fruit and vegetable consumption and cognitive decline in aging women.
AB  - We prospectively examined fruit and vegetable intake in relation to cognitive
      function and decline among aging women. Participants were followed from in 1976
      with biennial questionnaires, and food frequency questionnaires were administered
      in 1984, 1986, and every 4 years thereafter. From 1995 to 2001, we administered,
      by telephone, six cognitive tests measuring general cognition, verbal memory,
      category fluency, and working memory. We repeated assessments two years later for
      13,388 women (>90% follow-up). We averaged dietary intakes from 1984 through the
      first cognitive assessment, and used linear regression to obtain multivariable
      adjusted mean differences in performance and decline in performance across intake
      levels. Fruits were not associated with cognition or cognitive decline. However,
      total vegetable intake was significantly associated with less decline.
      Specifically, on a global score combining all tests, women in the highest
      quintile of cruciferous vegetables declined slower (by 0.04 unit; 95% confidence
      interval, 0.003, 0.07; p trend = 0.1) compared with the lowest quintile. Women
      consuming the most green leafy vegetables also experienced slower decline than
      women consuming the least amount (by 0.05 unit; 95% confidence interval, 0.02,
      0.09; p trend < 0.001). These mean differences were equivalent to those observed
      for women about 1 to 2 years apart in age.

PMID- 15852399
TI  - Distal spinal and bulbar muscular atrophy caused by dynactin mutation.
AB  - Impaired axonal transport has been postulated to play a role in the
      pathophysiology of multiple neurodegenerative disorders. In this report, we
      describe the results of clinical and neuropathological studies in a family with
      an inherited form of motor neuron disease caused by mutation in the p150Glued
      subunit of dynactin, a microtubule motor protein essential for retrograde axonal
      transport. Affected family members had a distinct clinical phenotype
      characterized by early bilateral vocal fold paralysis affecting the adductor and
      abductor laryngeal muscles. They later experienced weakness and atrophy in the
      face, hands, and distal legs. The extremity involvement was greater in the hands
      than in the legs, and it had a particular predilection for the thenar muscles. No
      clinical or electrophysiological sensory abnormality existed; however, skin
      biopsy results showed morphological abnormalities of epidermal nerve fibers. An
      autopsy study of one patient showed motor neuron degeneration and axonal loss in
      the ventral horn of the spinal cord and hypoglossal nucleus of the medulla.
      Immunohistochemistry showed abnormal inclusions of dynactin and dynein in motor
      neurons. This mutation of dynactin, a ubiquitously expressed protein, causes a
      unique pattern of motor neuron degeneration that is associated with the
      accumulation of dynein and dynactin in neuronal inclusions.

PMID- 15852400
TI  - Mitochondrial abnormalities in Alzheimer brain: mechanistic implications.
AB  - Reductions in cerebral metabolism sufficient to impair cognition in normal
      individuals also occur in Alzheimer's disease (AD). The degree of clinical
      disability in AD correlates closely to the magnitude of the reduction in brain
      metabolism. Therefore, we tested whether impairments in tricarboxylic acid (TCA)
      cycle enzymes of mitochondria correlate with disability. Brains were from
      patients with autopsy-confirmed AD and clinical dementia ratings (CDRs) before
      death. Significant (p < 0.01) decreases occurred in the activities of the
      pyruvate dehydrogenase complex (-41%), isocitrate dehydrogenase (-27%), and the
      alpha-ketoglutarate dehydrogenase complex (-57%). Activities of succinate
      dehydrogenase (complex II) (+44%) and malate dehydrogenase (+54%) were increased
      (p < 0.01). Activities of the other four TCA cycle enzymes were unchanged. All of
      the changes in TCA cycle activities correlated with the clinical state (p <
      0.01), suggesting a coordinated mitochondrial alteration. The highest correlation
      was with pyruvate dehydrogenase complex (r = 0.77, r2= 0.59). Measures to improve
      TCA cycle metabolism might benefit AD patients.

PMID- 15852402
TI  - Transient ischemic attack with infarction: a unique syndrome?
AB  - It is debated whether transient symptoms associated with infarction (TSI) are
      best considered a minor ischemic stroke, a subtype of transient ischemic attack
      (TIA), or a separate ischemic brain syndrome. We studied clinical and imaging
      features to establish similarities and differences among ischemic stroke, TIA
      without infarction, and TSI. Eighty-seven consecutive patients with TIA and 74
      patients with ischemic stroke were studied. All underwent diffusion-weighted
      imaging on admission. Symptom duration and infarct volume were determined in each
      group. Thirty-six patients (41.3%) with TIA had acute infarct(s). Although TIA
      related infarcts were smaller than those associated with ischemic stroke (mean,
      0.7 vs 27.3 ml; p < 0.001), there was no lesion size threshold that distinguished
      ischemic stroke from TSI. In contrast, the symptom duration probability density
      curve was not broad, but instead peaked early with only a few patients having
      symptoms for longer than 200 minutes. The probability density function for
      symptom duration was similar between TIA with or without infarction. The in
      hospital recurrent ischemic stroke and TIA rate was 19.4% in patients with TSI
      and 1.3% in those with ischemic stroke. TIA with infarction appears to have
      unique features separate from TIA without infarction and ischemic stroke. We
      propose identifying TSI as a separate clinical syndrome with distinct prognostic
      features.

PMID- 15852401
TI  - Interferon-alpha/beta-mediated innate immune mechanisms in dermatomyositis.
AB  - Dermatomyositis has been modeled as an autoimmune disease largely mediated by the
      adaptive immune system, including a local humorally mediated response with B and
      T helper cell muscle infiltration, antibody and complement-mediated injury of
      capillaries, and perifascicular atrophy of muscle fibers caused by ischemia. To
      further understand the pathophysiology of dermatomyositis, we used microarrays,
      computational methods, immunohistochemistry and electron microscopy to study
      muscle specimens from 67 patients, 54 with inflammatory myopathies, 14 with
      dermatomyositis. In dermatomyositis, genes induced by interferon-alpha/beta were
      highly overexpressed, and immunohistochemistry for the interferon-alpha/beta
      inducible protein MxA showed dense staining of perifascicular, and, sometimes all
      myofibers in 8/14 patients and on capillaries in 13/14 patients. Of 36 patients
      with other inflammatory myopathies, 1 patient had faint MxA staining of myofibers
      and 3 of capillaries. Plasmacytoid dendritic cells, potent CD4+ cellular sources
      of interferon-alpha, are present in substantial numbers in dermatomyositis and
      may account for most of the cells previously identified as T helper cells. In
      addition to an adaptive immune response, an innate immune response characterized
      by plasmacytoid dendritic cell infiltration and interferon-alpha/beta inducible
      gene and protein expression may be an important part of the pathogenesis of
      dermatomyositis, as it appears to be in systemic lupus erythematosus.

PMID- 15852403
TI  - Synergy of insulin-like growth factor-1 and exercise in amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the
      neuromuscular system resulting in paralysis and ultimately death. Currently, no
      effective therapy is prescribed for patients; however, several therapeutic
      strategies are showing promise. Either exercise or treatment with adeno
      associated virus/insulin-like growth factor-1 alone has therapeutic benefits in
      an amyotrophic lateral sclerosis transgenic mouse model. We show here that
      activity duration affects the therapeutic benefit associated with exercise, with
      6- and 12-hour exposure to a running wheel providing significant motor function
      benefits and increased survival. Remarkably, a combination of insulin-like growth
      factor-1 gene delivery and exercise has profound effects on survival and
      function, indicative of synergistic effects with exercise and insulin-like growth
      factor-1. Our results indicate that a drug treatment in combination with
      appropriate exercise may provide the most promising therapy for amyotrophic
      lateral sclerosis to date.

PMID- 15852404
TI  - Is freezing of gait in Parkinson's disease related to asymmetric motor function?
AB  - Freezing of gait (FOG) is a disabling phenomenon common in patients with advanced
      Parkinson's disease (PD). The cause of FOG is unclear. The objective of this
      study was to explore a novel hypothesis stating that FOG is related to asymmetric
      motor performance. We compared PD patients that experience FOG episodes (PD+FOG)
      with PD patients that do not (PD-FOG) and studied the relationship of FOG to
      asymmetry in gait and in rhythmic hand movement performance to determine whether
      potential FOG-related gait asymmetry is unique to walking or whether it is
      systemic. Subjects were tested in an "off" (unmedicated) and again in an "on"
      (medicated) state. Gait was more asymmetric in PD+FOG than in PD-FOG during "off"
      state (p = 0.005) and during "on" (p = 0.016). Rhythmicity of foot swing in one
      leg was correlated with the other leg in PD-FOG but not in PD+FOG. There was no
      difference in asymmetry in performance of rhythmic hand movements between the two
      groups. No correlation was found between asymmetry of clinical symptoms and gait
      asymmetry. Taken together, the results of this study suggest that bilateral
      uncoordinated gait and marked gait asymmetry, but not asymmetry in motor
      performance in general, are associated with FOG.

PMID- 15852405
TI  - Deep brain stimulation for dystonia: make the lame walk.

PMID- 15852406
TI  - Quality of life of husbands of women with breast cancer.
AB  - The life-threatening nature of breast cancer, along with the side effects of
      treatment, place great strain on patients and their families. Husbands may be
      especially vulnerable as the main source of support to patients. The present
      study compared the quality of life (QOL) of husbands of patients with breast
      cancer (HBC; n=79) to spouses of healthy wives (n=79). Additionally, associations
      between QOL and caregiver burden, social support, and coping were examined. HBC
      scored lower on general health, vitality, role-emotional, and mental health
      subscales of the Medical Outcomes Study (MOS) SF-36 than comparison group
      participants. No differences were found between groups on the physical
      functioning, role-physical, bodily pain, or social functioning subscales. Higher
      QOL in HBC was associated with less caregiver burden as evidenced by lower burden
      on the Illness Impact Form, lower use of emotion-focused coping on the Ways of
      Coping Questionnaire, and higher social support on the Interpersonal Support
      Evaluation List. Wife illness characteristics such as stage of disease and time
      since diagnosis were not related to QOL in husbands. These findings illuminate
      the need to support HBC, whose QOL suffers during the breast cancer experience.

PMID- 15852408
TI  - Neurocognitive complications after coronary artery bypass surgery.
AB  - Both short- and long-term cognitive changes continue to occur after coronary
      artery bypass grafting (CABG), but the pathophysiology of these neurobehavioral
      changes remains incompletely understood. The persistence of mild postoperative
      neurocognitive changes despite multiple improvements in the cardiopulmonary
      bypass procedure may be partially because of surgical populations being older and
      having more prevalent comorbid disease. The cause of the early postoperative
      changes is most likely multifactorial and may include ischemic injury from
      microemboli, hypoperfusion, and other factors resulting from major surgery.
      Several lines of evidence suggest that the late cognitive decline between 1 and 5
      years after surgery may be secondary to high rates of cerebrovascular disease
      among candidates for CABG. A history of hypertension and other risk factors for
      vascular disease is known to be associated with increased risk for long-term
      cognitive decline in community-dwelling elderly individuals. Cerebrovascular risk
      factors are also associated with silent magnetic resonance imaging abnormalities
      in patients undergoing CABG. Thus, whereas both short- and long-term
      postoperative cognitive changes have been associated with CABG, only the short
      term, transient changes appear to be directly related to the use of
      cardiopulmonary bypass.

PMID- 15852407
TI  - Results of combined-modality therapy for limited-stage small cell lung carcinoma
      in the elderly.
AB  - BACKGROUND: A Phase III trial was conducted by the North Central Cancer Treatment
      Group to determine whether chemotherapy (etoposide and cisplatin) plus either
      twice-daily radiotherapy (BIDRT) or once-daily radiotherapy (QDRT) resulted in a
      better outcome for patients with limited-stage small cell lung carcinoma (LD
      SCLC). No difference in survival was identified between the two arms. The current
      analysis examined the relation between age and outcome for patients treated
      during this trial. METHODS: The current study included 263 patients with LD-SCLC
      and an Eastern Cooperative Oncology Group performance status of < or = 2 who were
      randomized to receive QDRT or split-course BIDRT. The outcomes of the 209 (79%)
      younger patients (age < 70 years old) were compared with the 54 (21%) elderly
      patients (age > or = 70 years old). RESULTS: Elderly patients presented with
      significantly greater weight loss and poorer performance status. The 2-year and 5
      year survival rates were 48% and 22% for younger patients compared with 33% and
      17% for older patients (P = 0.14). One specific toxicity (i.e., Grade > or = 4
      pneumonitis [according to National Cancer Institute Common Toxicity Criteria])
      occurred in 0% of those patients age < 70 years compared with 6% of older
      patients (P = 0.008). Grade 5 toxicity occurred in 1 of 209 (0.5%) patients age <
      70 years compared with 3 of 54 (5.6%) older patients (P = 0.03). CONCLUSIONS:
      Despite having more weight loss, poorer performance status, increased pulmonary
      toxicity, and more deaths due to treatment, survival was not found to be
      significantly worse in older individuals. Fit elderly patients with LD-SCLC can
      receive combined-modality therapy with the expectation of relatively favorable
      long-term survival. Future research should focus on ways to decrease toxicity
      especially in the elderly.

PMID- 15852409
TI  - Induced tolerance to isohaemagglutinins.

PMID- 15852412
TI  - Characterization of antiproliferative and cytotoxic properties of the HSV-1
      immediate-early ICPo protein.
AB  - BACKGROUND: The identification of novel proteins displaying cytostatic and/or
      cytotoxic actions that could eventually be used for gene therapy is a major issue
      in cancer research. Data from the literature suggested that the immediate-early
      ICP0 protein from herpes simplex virus type 1 (HSV-1) could fulfill these
      properties as it had been observed that this protein is involved in arrest of
      cell growth at the G1/S and G2/M phases of the cell cycle and that deletion of
      ICP0 from HSV-1 or HSV-1-recombinant vectors significantly reduced their
      cytotoxicity. The molecular basis of its action is likely related to the ability
      of ICP0, which possesses E3-ubiquitin ligase activity, to target destruction of
      key cellular proteins, including centromeric proteins, resulting in abnormal
      chromosome segregation, unusual cytokinesis, and emergence of nuclear
      morphological aberrations. However, neither the gene therapy potential of ICP0 on
      its own nor its action on primary quiescent cells has been assessed to date. The
      aim of this work was therefore to evaluate the antiproliferative and cytotoxic
      properties of ICP0 on a human glioblastoma cell line and on quiescent primary
      cells, and to explore whether this protein has a potential for gene therapy of
      cancer. METHODS: HSV-1-based amplicon particles were generated following a
      recently described method that produces relatively high titers of vector stocks
      that are essentially free of helper virus. These vectors express either wild-type
      ICP0 or FXE, a RING finger mutated inactive form of ICP0, together with reporter
      green fluorescent protein (GFP). The vectors were used to infect Gli36 cells,
      which derive from a human glioblastome, and cultured rat primary cardiomyocytes
      and brain cells, two well-established models of non-dividing cells. Expression
      and localization of ICP0 and FXE, as well as their action on centromeres and
      nuclear morphology, were evaluated by Western blotting, indirect immune
      fluorescence, and confocal microscopy using specific antibodies and DAPI
      labeling. The impact of ICP0 on cell growth, toxicity, and viability was
      evaluated in the different cells using a variety of methods, including FACS
      analysis after propidium iodide and AnnexinV staining, crystal violet staining,
      clonogenic capability, caspase 3 activation, MTT tests, and release of lactate
      dehydrogenase, after infection with the different vectors. RESULTS: The three
      cell types under study showed high levels of transduction by amplicons and strong
      expression of GFP, ICP0, and FXE transgenic proteins. Wild-type ICP0, but not
      FXE, induced centromeric disruption, appearance of micronuclei, arrest of
      proliferation, and significant cell death in glioblastoma Gli36 cells. In
      contrast, neither micronuclei formation nor any other sign of cell toxicity could
      be observed in cultured primary cardiomyocytes or brain cells, as evaluated by
      MTT tests and crystal violet staining. Furthermore, in the case of
      cardiomyocytes, expression of ICP0 did not interfere with beating as cells
      continued to beat at the same frequency as non-infected cells for several days
      post-infection. Neither AnnexinV early staining nor caspase 3 activation was
      observed in dying infected Gli36 cells, suggesting that these cells were not
      entering apoptosis. In contrast, release of lactate dehydrogenase by infected
      Gli36 cells suggested a necrotic way of death. CONCLUSIONS: ICP0 induced a strong
      cytostatic action followed by significant cell death on the glioblastoma Gli36
      cell line. In contrast, neither cell death nor any other evidence of ICP0-induced
      toxicity affecting major physiological parameters was observed in primary
      cultured cardiomyoctes and brain cells, two models of primary non-cycling cells.
      These results suggest that ICP0 has gene therapy potential and could represent
      the first member of a novel family of directly acting proteins that could be used
      to treat cancers.

PMID- 15852413
TI  - Randomized clinical trial of continuous sutures or non-penetrating clips for
      radiocephalic arteriovenous fistula (Br J Surg 2004; 91: 1438-1442).

PMID- 15852414
TI  - Letter 1: Randomized clinical trial assessing impact of a lightweight or
      heavyweight mesh on chronic pain after inguinal hernia repair (Br J Surg 2005;
      92: 166-170).

PMID- 15852415
TI  - Letter 3: Randomized clinical trial assessing impact of a lightweight or
      heavyweight mesh on chronic pain after inguinal hernia repair (Br J Surg 2005;
      92: 166-170).

PMID- 15852416
TI  - Letter 2: Randomized clinical trial assessing impact of a lightweight or
      heavyweight mesh on chronic pain after inguinal hernia repair (Br J Surg 2005;
      92: 166-170).

PMID- 15852417
TI  - Early impact of centralization of oesophageal cancer surgery services (Br J Surg
      2004; 91: 1630-1632).

PMID- 15852418
TI  - Five-year follow-up of a randomized trial to assess pain and numbness after
      laparoscopic or open repair of groin hernia (Br J Surg 2004; 91: 1570-1574).

PMID- 15852419
TI  - Systematic review and meta-analysis of technique for closure of the pancreatic
      remnant after distal pancreatectomy.
AB  - BACKGROUND: Appropriate closure of the pancreatic remnant after distal
      pancreatectomy is still debated. A variety of procedures have been recommended to
      reduce the frequency of pancreatic fistula. This review quantitatively compares
      the available techniques. METHODS: Original articles and abstracts published up
      to the end of June 2004 were searched without language restriction in the
      Cochrane Controlled Trials Register, Medline and Embase. Three reviewers
      independently assessed each study's eligibility and quality, and extracted the
      data. A random effects model was performed using weighted odds ratios. RESULTS:
      Only ten of 262 articles could be included, two randomized clinical trials and
      eight observational studies. Reported postoperative morbidity varied from 13.3 to
      64 per cent. The primary outcome measure, pancreatic fistula rate, occurred
      within the range 0-60.9 per cent. Meta-analysis of the six studies comparing
      stapler versus hand-sutured closure showed a non-significant combined odds ratio
      for occurrence of a pancreatic fistula of 0.66 (95 per cent confidence interval
      0.35 to 1.26, P = 0.21) in favour of stapler closure. CONCLUSIONS: The quality
      and quantity of information extracted from the available trials are insufficient
      to enable any firm conclusion to be drawn on the optimal surgical technique of
      pancreatic stump closure; there is a trend in favour of the stapling technique.

PMID- 15852421
TI  - Injectable bulking agents for treating faecal incontinence.
AB  - BACKGROUND: Reports of the use of injectable bulking agents for faecal
      incontinence are currently confined to a small number of pilot studies. However,
      the use of these agents is rapidly becoming widespread based on this limited
      knowledge. METHODS: This review provides an overview of the products available
      and the methods of delivery based on the pilot studies, selected articles
      reporting experience of these agents in urology, plastic surgery and laryngology,
      and some animal studies. RESULTS AND CONCLUSIONS: Although bulking agents have
      been used to treat urinary incontinence for over four decades, their use in
      faecal incontinence has so far been limited. The large choice of products now
      available and the lack of a defined injection strategy will hamper efforts to
      produce meaningful prospective randomized trials.

PMID- 15852422
TI  - Ischaemic preconditioning in transplantation and major resection of the liver.
AB  - BACKGROUND: Ischaemia-reperfusion injury (IRI) contributes significantly to the
      morbidity and mortality of transplantation and major resection of the liver. Its
      severity is reduced by ischaemic preconditioning (IP), the precise mechanisms of
      which are not completely understood. This review discusses the pathophysiology
      and role of IP in this clinical setting. METHODS: A Medline search was performed
      using the keywords 'ischaemic preconditioning', 'ischaemia-reperfusion injury',
      'transplantation' and 'hepatic resection'. Additional articles were obtained from
      references within the papers identified by the Medline search. RESULTS AND
      CONCLUSION: The mechanisms underlying hepatic IRI are complex, but IP reduces the
      severity of such injury in several animal models and in recent human trials.
      Increased understanding of the cellular processes involved in IP is of importance
      in the development of treatment strategies aimed at improving outcome after liver
      transplantation and major hepatic resection.

PMID- 15852423
TI  - Diagnostic peritoneal lavage - an obituary.

PMID- 15852424
TI  - Laparoscopic surgery for colorectal cancer.

PMID- 15852426
TI  - Short-term cost effectiveness and long-term cost analysis comparing laparoscopic
      Nissen fundoplication with proton-pump inhibitor maintenance for gastro
      oesophageal reflux disease.
AB  - BACKGROUND: This study examined the short-term cost-effectiveness and long-term
      cost of laparoscopic Nissen fundoplication (LNF) versus maintenance proton-pump
      inhibitor (PPI) medication for severe gastro-oesophageal reflux disease (GORD)
      based on a randomized clinical trial. METHODS: Costs and outcomes for 12 months
      were obtained from the first 100 patients in the trial. Detailed costing was
      performed using resource use data from hospital records and general
      practitioners' notes. Short-term incremental cost-effectiveness ratios,
      calculated as the cost difference divided by the effectiveness difference between
      LNF and PPI therapy, were analysed using net benefit and bootstrap approaches.
      Long-term cost was examined using sensitivity analyses incorporating published
      data from other large series. RESULTS: The incremental cost of LNF compared with
      PPI therapy per additional patient returned to a physiologically normal acid
      score (less than 13.9) at 3 months was pound5515 (95 per cent confidence interval
      (c.i.) pound3655 to pound13 400) and the incremental cost per point improvement
      in combined Gastro-Intestinal and Psychological Well-being score at 12 months was
      pound293 (90 per cent c.i. pound149 to pound5250). On average, LNF cost pound2247
      (95 per cent c.i. pound2020 to pound2473) more than PPI therapy in year 1 and
      broke even in year 8. Break-even was highly sensitive to hospital unit costs but
      less sensitive to PPI ingestion rate after LNF, LNF reoperation rate, PPI relapse
      rate, future PPI price, PPI dose escalation and discount rate. CONCLUSION: From a
      National Health Service perspective, LNF may be cost-saving after 8 years
      compared with maintenance PPI therapy for the treatment of GORD.

PMID- 15852425
TI  - Colorectal cancer and the CHEK2 1100delC mutation.
AB  - The CHEK2 1100delC mutation was recently identified as a low-penetrance breast
      cancer susceptibility allele. The mutation occurred more frequently in families
      with clustering of breast and colorectal cancers (CRCs) than in families with
      clustering of breast cancer only. Hence, the 1100delC mutation could also be a
      low-penetrance CRC susceptibility allele. To test this hypothesis, we examined
      the mutation in 629 unselected CRC cases, 230 controls, and 105 selected CRCs
      diagnosed in patients before age 50. The mutation was observed in 1.6% of
      unselected patients and in 0.3% of controls (Not significant (NS)). After
      stratifying unselected patients according to defined genetic risk (on the basis
      of age at diagnosis and family history of colorectal and endometrial cancer), the
      highest frequency was observed in high-risk patients (12.5%), followed by
      moderate-risk patients (3.3%), and was lowest in low-risk patients (1.0%,
      P(trend) 0.014). In selected patients, 1.6% carried the mutation (NS). Subgroup
      analyses for tumor localization, gender, and age at diagnosis did not reveal an
      association with the 1100delC genotype. In addition, a pooled analysis, combining
      data of one published study in unselected CRC cases and our study, also did not
      reveal an association. In conclusion, the frequency of the 1100delC genotype was
      neither significantly increased in unselected CRC patients nor in selected CRC
      patients diagnosed before age 50. However, after stratifying unselected CRC
      patients according to defined genetic risk, a significant trend of increasing
      frequency was observed. Together, the results are consistent with a low
      penetrance effect (OR 1.5-2.0) of the CHEK2 1100delC on CRC risk. Large case
      control studies are required to clarify the exact role of the CHEK2 1100delC
      mutation in CRC.

PMID- 15852427
TI  - Efficient 1,5-chirality transfer in palladium-catalyzed allylic alkylations of
      chelated amino acid ester enolates.

PMID- 15852428
TI  - Aminolysis route to monodisperse titania nanorods with tunable aspect ratio.

PMID- 15852429
TI  - Supramolecular interactions as determining factors of the geometry of metallic
      building blocks: tetracarboxylate dimanganese species.

PMID- 15852430
TI  - Insight into and practical application of pH-controlled asymmetric transfer
      hydrogenation of aromatic ketones in water.

PMID- 15852431
TI  - ALK-positive diffuse large B-cell lymphoma.
AB  - Anaplastic lymphoma kinase (ALK) positive diffuse large B-cell lymphoma (DLBCL)
      is a rare subtype of non-Hodgkins lymphoma. Five such cases have been described
      in children. We present a 9-year-old boy, in whom diagnosis of DLBCL has been
      established in addition to congenital multiple enchondromatosis.
      Immunohistopathological evaluation of tumor biopsy established the final
      diagnosis of ALK + DLBCL. The clathrin gene (CLTC)-ALK fusion underlying aberrant
      expression of ALK in the present case was demonstrated by interphase fluorescence
      in situ hybridization (FISH) using break-apart rearrangement probes for ALK and
      CLTC. The disease in this patient was highly resistant to applied chemotherapy
      regimens and to radiotherapy. Analysis of the disease course in our patient and
      review of other cases reported previously show that ALK + DLBCL can be an
      aggressive malignancy that can be cured with conventional chemotherapy protocols
      only at stage of localized disease.

PMID- 15852432
TI  - Transfusion related acute lung injury: a pediatric perspective.
AB  - Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion
      associated mortality. TRALI occurs in children and adults, but the syndrome has
      not been reviewed from a pediatric perspective. We reviewed the literature on
      TRALI from a pediatric perspective. TRALI has been documented in pediatric
      patients, especially in the setting of hematologic malignancy. Additional TRALI
      cases have been reported in pediatric patients with a variety of diagnoses. TRALI
      is likely to be much more common than previously appreciated in the pediatric
      patient population. TRALI should be considered in the differential diagnosis of
      all pediatric patients who develop new acute lung injury (ALI) or acute
      respiratory distress syndrome (ARDS) during or within six hours of a blood
      product transfusion. When a case of TRALI is suspected, a transfusion reaction
      report to the blood bank is important to initiate the investigation and identify
      the implicated donor.

PMID- 15852433
TI  - Major depression as a risk factor for early institutionalization of dementia
      patients living in the community.
AB  - OBJECTIVE: Although depression is known to be frequently associated with
      dementia, it is nonetheless under-diagnosed and under-treated among this patient
      population. Its effect on outcome for dementia patients is thought to be
      substantial, because depression appears to induce higher than normal rates of
      disability as well as supplementary cognitive decline. The aim of this study was
      to measure the impact of major depression on the institutionalization rate of
      community-dwelling dementia patients. DESIGN: Prospective cohort study. SETTING:
      Paris, France. PARTICIPANTS: Three-hundred forty-eight consecutive dementia
      outpatients of a geriatric clinic (mean age: 81 years, 69.8% women, 65.5%
      dementia of Alzheimer's type, mean baseline MMSE score: 20.5), followed between
      1997 and 2002 (mean follow-up: 20.5 months). RESULTS: Twenty-five percent of the
      patients met the criteria of major depression at baseline, and only 30.3% of
      these received antidepressant medication. Major depression at baseline was
      independently associated with nursing home admission within one year of the
      baseline assessment. Antidepressant medication tended to protect against this
      outcome, but not to a statistically significant extent. CONCLUSIONS: Major
      depression at baseline is an independent risk factor for early
      institutionalization of dementia sufferers. Early institutionalization is defined
      in this study as nursing home placement within a year of diagnosis with dementia
      at our specialized outpatient center. The study highlights the need for better
      management of depression among dementia outpatients. Further investigation is
      needed to evaluate the protective effect of antidepressant medication (and/or non
      pharmacological therapies) on the institutionalization rate.

PMID- 15852434
TI  - The role of adjuvant chemotherapy in children and adolescents with surgically
      resected, high-risk adult-type soft tissue sarcomas.
AB  - PURPOSE: This analysis evaluates whether adjuvant chemotherapy can be recommended
      for high-risk, surgically-resected, adult-type non-rhabdomyosarcoma soft tissue
      sarcomas (NRSTS) within the new European Pediatric Soft Tissue Sarcoma Study
      Group (EpSSG) protocol. The Italian and German Cooperative Groups reviewed their
      data-bases, analyzing patients classified as group I-II, with high-grade tumor
      (G3) larger than 5 cm in size. METHODS: The analysis included 36 patients, and
      compared the clinical features and outcome of the group of 21 patients who
      received chemotherapy versus the group of 15 patients treated with local
      therapies only. RESULTS: For the series as a whole, 5-year event-free survival
      (EFS), metastasis-free survival (MFS), and overall survival (OS) were 26.2%,
      34.0%, and 37.5%, respectively. In patients treated with chemotherapy, MFS and OS
      were 49.5% and 41.5% (median time to relapse: 13 months). In patients who did not
      receive chemotherapy, MFS and OS were 0% and 23.8% (median time to relapse: 3
      months). CONCLUSION: The role of adjuvant chemotherapy in NRSTS is still
      uncertain, however, the current retrospective analysis showed that: (1) despite
      the globally good prognosis of grossly-resected cases, patients with G3 and large
      size have a high-risk of metastatic spread, and (2) MFS appears to be better in
      patients who had chemotherapy. Based in part on these results, and in accordance
      with recent suggestions coming from the literature on adult sarcomas, the EpSSG
      NRSTS protocol will recommend adjuvant chemotherapy in high-risk surgically
      resected patients.

PMID- 15852435
TI  - Positive affect and its relationship to free recall memory performance in a
      sample of older Dutch adults from the Maastricht Aging Study.
AB  - OBJECTIVE: A Dutch translation of the Positive and Negative Affect Scale (PANAS)
      was used to measure Positive Affect (PA) and its relationship to episodic memory
      in a sample of Dutch adults between the ages of 40 to 82 years. Specifically, the
      role of PA was examined as a predictor of performance on a serial list learning
      task that included a recognition and free recall component. METHODS: Participants
      were divided into two age groupings representing middle-age (40 to 64 years) and
      older (65 to 82 years) adults with respect to the study sample. RESULTS: PA was
      not related to recognition performance in either age grouping. In the older age
      group, however, PA predicted free recall. CONCLUSIONS: PA facilitated episodic
      memory in older adults when unsupported tasks conditions were present that placed
      heavy demands on processing resources.

PMID- 15852436
TI  - A pilot study examining the effectiveness of maintenance Cognitive Stimulation
      Therapy (MCST) for people with dementia.
AB  - BACKGROUND: A recent randomised controlled trial on Cognitive Stimulation Therapy
      (CST) identified the need to evaluate its more long-term benefits for people with
      dementia. This study evaluates the effectiveness of a weekly maintenance CST
      programme for people with dementia in residential care. METHOD: Thirty-five
      people with dementia were included, following on from a seven-week twice-weekly
      study of CST. The maintenance CST sessions ran in two residential homes using a
      once a week programme of CST over an additional 16 weeks. Two control homes did
      not receive the maintenance intervention. RESULTS: Using repeated measures
      ANOVAS, there was a continuous, significant improvement in cognitive function
      (MMSE) for those receiving MCST (CST+maintenance CST sessions) as compared to CST
      alone or no treatment (p = 0.012). There were no effects on quality of life,
      behaviour or communication following maintenance sessions. The initial cognitive
      improvements following CST were only sustained at follow-up when followed by the
      programme of maintenance CST sessions. CONCLUSIONS: The cognitive benefits of CST
      can be maintained by weekly sessions for around 6 months. A large-scale, multi
      centre maintenance CST trial is required to clarify potential longer-term
      benefits of maintenance CST for dementia.

PMID- 15852437
TI  - Switching from donepezil to galantamine: a double-blind study of two wash-out
      periods.

PMID- 15852438
TI  - Does education moderate neuropsychological impairment in late-life depression?
AB  - OBJECTIVE: The increased resistance of better-educated individuals to the
      cognitive effects of neuropathology has been conceptualized as reflecting brain
      reserve. This study examined whether educational level influences the degree of
      neuropsychological impairment associated with late-life depression. METHODS: The
      neuropsychological performances of 115 older depressed patients and of 44
      comparison subjects of similar age and education were compared as a function of
      educational level. RESULTS: While depressed patients performed worse than
      comparison subjects on all the measures, the severity of this impairment (with
      respect to comparison subjects) did not differ with the educational level of the
      patients. CONCLUSIONS: Brain reserve, as indexed by the patients' level of
      education, does not mitigate the cognitive decrements associated with late-life
      depression.

PMID- 15852439
TI  - The Center for Epidemiologic Studies Depression Scale in older Chinese:
      thresholds for long and short forms.
AB  - OBJECTIVE: No study has examined the diagnostic validity of the Center for
      Epidemiologic Studies Depression Scale (CES-D) in the Chinese elderly. This study
      aims to determine appropriate cutoffs for the 20- (CESD-20) as well as a ten-item
      (CESD-10) version of the instrument. Data were also provided, based on simulated
      scoring, for the diagnostic performance of the scales when using dichotomous
      instead of 4-point rating scales. METHODS: Three hundred and ninety eight persons
      aged 60 +referred for psychiatric assessment by a physician were administered the
      CES-D as well as given an independent psychiatric assessment. A spectrum of
      depression diagnosis as the criterion was used to assess the diagnostic validity
      of the CES-D. RESULTS: The ten and the 20-item version of the CES-D, regardless
      of scoring method, produced essentially identical performance indices. The
      optimal thresholds were 12 and 22 for CESD-10 and CESD-20 respectively, and based
      on these thresholds, sensitivity, specificity, positive predictive value and
      negative predictive value were 0.76, 0.55, 0.57 and 0.74 for CESD-10, and 0.75,
      0.51, 0.55 and 0.72 for CESD-20. With both ends of the rating scale collapsed to
      create dichotomous items, the optimal thresholds became 4 for CESD-10 and 7 for
      CESD-20, and the corresponding performance indices were 0.67, 0.58, 0.56 and 0.69
      for CESD-10, and 0.70, 0.58, 0.57 and 0.70 for CESD-20. CONCLUSIONS: The ten-item
      version can be used in lieu of the 20-item version, and a dichotomous response
      format would probably work as well as the original four-point format, in order to
      simplify administration for elderly persons.

PMID- 15852440
TI  - Does modafinil have the potential to improve disrupted sleep patterns in patients
      with dementia?

PMID- 15852441
TI  - Electron ionization mass spectrometry in the analysis of substituted
      stilbenethiols.

PMID- 15852442
TI  - Laser ablation generation of cluster ions from concentrated sulfuric and selenic
      acids.
AB  - The generation and identification of novel homo- and hetero-polyacid clusters was
      achieved using a standard matrix-assisted laser desorption/ionization time-of
      flight (MALDI-TOF) mass spectrometer. The formation of several singly charged
      species was achieved via the interaction of a laser beam with concentrated
      sulfuric acid, selenic acid or their mixtures, applied on a graphite
      microcrucible. A higher yield of the species was observed in the negative
      detection mode, where sulfuric acid adducts HSO(4) (-) . mH(2)SO(4) (m = 0-3) and
      HSO(4) (-) . mH(2)SO(4) . SO(3) (m = 1, 2), and selenic acid adducts HSeO(4) (-),
      HSeO(4) (-) . X (X = SeO(3), H(2)SeO(4), 2SeO(3), H(2)SO(4) . SeO(3)) and
      NaSeO(4) (-). Y (Y = H(2)SeO(4), H(2)SeO(4). SeO(3), 2H(2)SO(4), H(2)SeO(4) .
      2SeO(3), 2H(2)SeO(4) . SeO(3), 3H(2)SeO(4)), were identified. In the mass spectra
      of the mixture of acids, besides the homo-polyacidic adducts, eleven mixed
      species containing both sulfuric and selenic acid molecules or ions were
      identified, of which the heaviest was found to correspond to NaSeO(4) (-) .
      H(2)SeO(4) . 3SO(3). The stoichiometry of the species was confirmed using
      isotopic pattern modeling.

PMID- 15852443
TI  - The CIDI as an instrument for diagnosing depression in older Turkish and Moroccan
      labour migrants: an exploratory study into equivalence.
AB  - OBJECTIVE: The number of elderly migrants from Turkey and Morocco in Western
      Europe will increase sharply in the coming decades. Many of these migrants seem
      to have mental health problems. As mental health care programs are based on DSM
      criteria, there is a need for diagnostic instruments with good psychometric
      properties. This exploratory study examines the presence of construct bias,
      method bias and item bias in the Composite International Diagnostic Interview
      (CIDI) Basis Life time version 2.1 in elderly Turkish and Moroccan men and women.
      METHOD: From a community based health survey four groups of migrants aged 55-74
      were selected for semi-structured interviews including the CIDI depression
      section. Data included interview transcriptions and observations of 11
      respondents in each group (Turkish men, Turkish women, Moroccan men, and Moroccan
      women). The data were analysed using qualitative techniques. RESULTS: Construct
      bias, method bias and item bias of the CIDI was found in all groups. The poor
      match between the CIDI on the one hand and the taboo on mental health problems
      and the poor level of education of the respondents can partly explain this bias.
      CONCLUSIONS: The use of the CIDI in elderly migrants of Moroccan and Turkish
      descent is problematic, due to the presence of construct, method and item bias.

PMID- 15852444
TI  - Effects of memantine on behavioural symptoms in Alzheimer's disease patients: an
      analysis of the Neuropsychiatric Inventory (NPI) data of two randomised,
      controlled studies.
AB  - INTRODUCTION: Behavioural symptoms are common in moderate to severe Alzheimer's
      disease (AD). We have analysed the databases of two randomised studies with
      regard to the effects of memantine treatment on behavioural symptoms, measured
      using the 12-item version of the Neuropsychiatric Inventory (NPI). SUBJECTS: The
      monotherapy study (memantine only) reported by Reisberg et al. (2003) involved
      252 patients with baseline MMSE total score of between 3 and 14, whereas the
      combination study (memantine and donepezil) reported by Tariot et al. (2004)
      comprised 404 patients with MMSE scores of between 5 and 14. In both studies,
      patients received 10 mg memantine b.i.d. or matching placebo, and lived in the
      community. METHODS: For both studies NPI total and individual domains scores were
      analysed in the ITT population. For the monotherapy study a dichotomised analysis
      was performed separately for patients who had behavioural symptoms at baseline
      and for those without pre-existing symptoms. Furthermore, a factor analysis was
      used to identify any behavioural clusters within the patient population. RESULTS:
      In both studies, the change in NPI total scores at endpoint was consistently in
      favour of memantine treatment, reaching statistical significance in the
      combination study (p = 0.002). Memantine treatment showed a significant
      beneficial effect in comparison to placebo treatment in the NPI
      agitation/aggression domain in both studies (p = 0.008; p = 0.001). The
      dichotomised analysis of the monotherapy study showed that there was
      significantly less agitation/aggression emerging in the memantine-treated group
      compared to placebo (p = 0.003). Factor analysis showed that hyperactivity
      accounted for 27% of the data variance. CONCLUSIONS: Memantine has a beneficial
      effect on the behavioural symptoms of patients with moderate to severe AD, with
      the most pronounced effect on agitation/aggression.

PMID- 15852445
TI  - Increased renal hypertrophy in diabetic mice genetically modified at the
      haptoglobin locus.
AB  - BACKGROUND: The human haptoglobin (Hp) gene is polymorphic with two functional
      classes of alleles, denoted 1 and 2. We have demonstrated in three longitudinal
      studies and several cross-sectional studies that the Hp genotype is an
      independent risk factor for diabetic vascular disease. These studies have
      presented a compelling argument that diabetic individuals homozygous for the Hp 1
      allele are at decreased risk of vascular complications as compared to diabetic
      individuals with the Hp 2 allele. METHODS: The naturally occurring (wild type)
      mouse Hp is a class 1 Hp allele. We examined renal hypertrophy in wild-type mice,
      Hp knockout mice (Hp 0), and in mice with the Hp 2 allele (Hp 2) with and without
      diabetes. RESULTS: In the absence of diabetes, we found that renal hypertrophy
      was significantly increased in Hp 0 mice and that this could be prevented with
      vitamin E. There was no difference between wild type and Hp 2 mice with regard to
      renal hypertrophy in the absence of diabetes. However, in the presence of
      diabetes, Hp 2 mice demonstrated a significant increase in renal hypertrophy as
      compared to wild-type mice. CONCLUSIONS: These results support a direct linkage
      between diabetic vascular disease and the Hp genotype. These Hp-modified mice may
      serve as a platform on which to test a variety of pharmacological agents in order
      to decrease diabetic vascular disease.

PMID- 15852446
TI  - The role of vitamin D in protecting type 1 diabetes mellitus.
AB  - The relationship between autoimmune diabetes or type 1 diabetes mellitus and
      vitamin D has been reported in the literature. Many factors, environmental and
      genetic, have been known, as risk factors, to cause both type 1 diabetes and
      vitamin D deficiency. Vitamin D treatment has improved or prevented type 1
      diabetes mellitus in animals and humans. Vitamin D also has been known to protect
      from autoimmune diseases in animal models. Therefore, it would be interesting to
      review the role of vitamin D in type 1 diabetes mellitus.

PMID- 15852448
TI  - Simplex maximization of the correlation coefficient for DNA sizing analysis by
      capillary electrophoresis.
AB  - The separation of DNA molecules in polymeric solution by capillary
      electrophoresis involves the optimization of several variables, such as polymer
      solution concentration, electric field separation, temperature, etc. The
      optimization of each variable individually usually is a time-consuming process
      and the results may reach a false optimum point. Chemometric methods are suitable
      to be applied in such cases in which a number of variables can be optimized
      simultaneously. The simplex is a chemometric method that can perform such a task
      easily and efficiently. In this study, a simplex method was carried out to
      maximize the correlation coefficient (r(2)) of a logarithmic plot of mobility
      (mu) vs. base pair (bp), which was obtained from the separation of DNA fragments
      of size between 75 and 4072 bp. The simplex showed three vertexes with r(2) >
      0.98 and the vertex 21 showing the highest resolution. For the fragments between
      201 and 2036 bp, the r(2) increased to 0.992 with and relative standard deviation
      (RSD) lower than 0.2% (inter- and intra-day variation). The precision of the
      method in determining the size of a PCR DNA fragment was carried out using a 1
      kbp DNA ladder. With the addition of an internal standard to the sample, the
      precision could be further improved.

PMID- 15852450
TI  - Development of a multi-target screening analysis for 301 drugs using a QTrap
      liquid chromatography/tandem mass spectrometry system and automated library
      searching.
AB  - A new multi-target screening (MTS) procedure for drugs in blood and urine for
      toxicological analysis has been developed using a hybrid triple-quadrupole linear
      ion trap mass spectrometer (QTrap) for the fast detection and identification of
      301 forensically important drugs, e.g. tranquilizers (benzodiazepines),
      hypnotics, drugs of abuse (opiates, cocaine, amphetamines, cannabinoids),
      antidepressants, neuroleptics, and some cardiac drugs, in one single liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) analysis. Samples were
      extracted either with liquid-liquid extraction or solid-phase extraction. A
      multiple reaction monitoring (MRM) as survey scan and an enhanced product ion
      (EPI) scan as dependent scan were performed in an information-dependent
      acquisition (IDA) experiment. Finally, drug identification was carried out by
      library search with a newly developed MS/MS library based on EPI spectra at three
      different collision energies in positive mode. The advantage of this newly
      developed method is the possibility to detect and identify 301 drugs in one
      single LC/MS/MS run.

PMID- 15852451
TI  - Electron ionization mass spectra of indolenines obtained using sector and ion
      trap mass spectrometers.
AB  - The electron impact (EI)-induced fragmentations of 18 indolenines were studied
      using both double-focusing and ion trap mass spectrometers. The compounds used in
      this study were synthesized to provide correlations of characteristic fragment
      ions with specific structural differences. In 2-hydroxyindolenines the hydroxy
      group was involved in a major fragmentation process by interacting with the ester
      side chain to generate an alpha,beta-unsaturated gamma-lactone structure, with
      concomitant loss of the corresponding alcohol. In contrast, loss of an alkyl
      radical, derived solely from the 2-alkoxy group, is a major primary decomposition
      process for 2-alkoxyindolenines. EI-MS analyses using sector and ion trap
      spectrometers resulted in similar fragmentation patterns.

PMID- 15852452
TI  - Positive electrospray liquid chromatography/mass spectrometry using high-pH
      gradients: a way to combine selectivity and sensitivity for a large variety of
      drugs.

PMID- 15852453
TI  - Does arm length indicate cognitive and functional reserve?
AB  - BACKGROUND: This study aimed to examine whether arm length and height were
      associated with cognitive and functional abilities. METHODS: Screening interviews
      were conducted in 235 community dwelling individuals aged 65 and over. The
      assessment scales included the Korean version of modified Mini-Mental State
      Examination (K-mMMSE) for cognition, and the Korean Instrumental Activities of
      Daily Living (K-IADL) for functional ability. All the participants were examined
      clinically and a diagnosis of dementia was ascertained. Anthropometric
      measurements included total arm span and height. RESULTS: Both arm length and
      height correlated significantly with the cognitive and functional scales. In the
      multivariate regression models, their associations were significant, independent
      of age, sex, education, and other variables. Shorter arm length was also
      significantly associated with dementia; while, height lost significance after an
      adjustment for the potential confounders. CONCLUSIONS: Arm length and height
      could indicate cognitive and functional ability. Arm length, which was known to
      be less prone to degenerative processes, might be more stable as an indicator for
      cognitive and functional reserve capacity than height.

PMID- 15852455
TI  - Effects coding in discrete choice experiments.
AB  - This paper discusses the inherent problems associated with applying dummy coding
      when including a fixed comparator in a discrete choice experiment, and seeks to
      illustrate the misinterpretations that may arise if the analyst is not aware of
      the problem. This note provides two examples of possible misinterpretations with
      dummy coding and how it is solved with the use of effects coding.

PMID- 15852454
TI  - Dementia in Parkinson's disease: a post-mortem study in a population of brain
      donors.
AB  - OBJECTIVE: To identify factors associated with dementia in a cohort of
      Parkinson's disease (PD) brain donors and determine whether its presence may
      influence the clinical phenotype of the disease. METHODS: We included 67
      consecutive patients with a clinical and pathological diagnosis of PD, who while
      alive, consented to donate their brains to the University of Miami Brain
      Endowment Bank(TM). Dementia and psychiatric complications of PD were diagnosed
      according to established criteria. Case histories were abstracted and reviewed
      and comparisons between PD patients with (PD-D, n = 34) and without (PD, n = 33)
      dementia were made. RESULTS: Age at death, age at disease onset and disease
      duration did not differ significantly between PD-D and PD patients. Other
      symptoms were similar in both groups. Visual hallucinations and bilateral
      symptoms at diagnosis were significantly higher in PD-D patients. No association
      between dementia and overall survival duration was found. Although the frequency
      of depression and psychosis was higher in the PD patients with dementia no
      statistical significance was reached. The overall lifetime prevalence of dementia
      in our group was 50.7%. CONCLUSIONS: Visual hallucinations and bilateral symptoms
      were associated with dementia in our cohort of PD brain donors. No association
      between dementia and survival duration was found. Understanding the influence of
      dementia on the clinical phenotype of the disease and predicting its development
      is essential for the successful management of PD.

PMID- 15852456
TI  - Allocating health care resources under risk: risk aversion and prudence matter.
AB  - In a recent contribution to this journal, M. Hoel correctly shows that under risk
      aversion the allocation of health resources should be directed to health
      conditions for which the expected outcomes are below average. In this letter we
      show that besides risk aversion, the degree of absolute prudence (to be defined
      in the text) also matters to obtain an optimal allocation.

PMID- 15852457
TI  - Structure and function studies of glucagon-like peptide-1 (GLP-1): the designing
      of a novel pharmacological agent for the treatment of diabetes.
AB  - Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide secreted from
      gut endocrine cells in response to nutrient ingestion. The multifaceted actions
      of GLP-1 include the following: (1) the stimulation of insulin secretion and of
      its gene expression, (2) the inhibition of glucagon secretion, (3) the inhibition
      of food intake, (4) the proliferation and differentiation of beta cells, and (5)
      the protection of beta-cells from apoptosis. The therapeutic utility of the
      native GLP-1 molecule is limited by its rapid enzymatic degradation by a serine
      protease termed dipeptidyl peptidase-IV (DPP-IV). The present article reviews the
      research studies aimed at elucidating the biosynthesis, metabolism, and molecular
      characteristics of GLP-1 since it is from these studies that the development of a
      GLP-1-like pharmacological agent may be derived.

PMID- 15852458
TI  - Rivastigmine in the treatment of dementia in Alzheimer's disease in adults with
      Down syndrome.

PMID- 15852459
TI  - Childhood conduct problems, stages of Alzheimer's disease, and physical
      aggression against caregivers.
AB  - OBJECTIVE: To assess the prevalence of physical aggression against caregivers by
      Alzheimer's patients. METHOD: One hundred and ninety-eight individuals with
      dementia, primarily Alzheimer's disease (AD) were evaluated with the Cohen
      Mansfield Agitation Inventory, the Mini Mental Status Examination, two measures
      of Activities of Daily Living, portions of the Conflict Tactics Scale to measure
      physical aggression against partner, questions about conduct problems during
      childhood/adolescence of the patients, and chart records of delusion and
      paranoia. RESULTS: 25% of the patients engaged in physical aggression against
      their caregivers in the past year, and 33% of the patients engaged in some act of
      physical aggression against any individual in the past two weeks. Physical
      aggression against a caregiver was more likely in the middle (34%) than the early
      stage of AD (4%). Physical aggression against a partner and agitation were more
      likely if the patient had a history of symptoms of conduct disorder. Delusions
      and paranoia were both associated with general physical aggression and general
      verbal aggression but not physical aggression against a caretaker. CONCLUSIONS:
      25% of Alzheimer's disease and Multi-Infarct dementia patients engaged in acts of
      physical aggression against their caregivers. The rate of aggression seen in this
      clinical sample was much higher than the rate of physical aggression in a
      community sample of the elderly.

PMID- 15852460
TI  - Depressive symptom quality and neuropsychological performance in dementia.
AB  - BACKGROUND: It is unknown to what extent depression and cognitive dysfunction are
      related in subjects with dementia. A limitation of earlier studies is that only
      general measures of depression have been studied. METHODS: In a sample of 60
      subjects with dementia according to DSM-III-R criteria depressive symptoms were
      divided into factors of mood and motivation disturbance according to a principal
      components analysis. Correlations were computed between the factor scores and the
      performance on a number of specific neuropsychological tests. As the symptom
      content of motivation disturbance suggests subcorticofrontal dysfunction it was
      hypothesized that this factor is related to impaired executive functions.
      RESULTS: 77% of the depressive symptoms contributed to the dimension of
      motivation disturbance and most of these symptoms occurred outside the context of
      a major depressive episode. Our hypothesis was supported by a significant
      negative correlation between motivation symptoms and semantic verbal fluency.
      This relationship seems to have specificity, as both the dimensions of mood
      symptoms and of general depressive symptoms did not correlate significantly with
      specific neuropsychological test scores. CONCLUSIONS: The division of depressive
      symptoms in factors of mood and motivation disturbance contributes to insight
      into the relationship between depression and cognitive dysfunction in dementia.
      An advantage of the motivation disturbance factor compared to the regular apathy
      scales is that it consists of depressive symptoms. Therefore, it becomes evident
      that apathy or impaired motivation may occur in patients with dementia both in
      and outside the context of a depressive syndrome.

PMID- 15852461
TI  - Detecting effects of donepezil on visual selective attention using signal
      detection parameters in Alzheimer's disease.
AB  - BACKGROUND: Attentional function is impaired in Alzheimer's disease (AD).
      Moreover, attention is mediated by acetylcholine. But, despite the widespread use
      of acetylcholinesterase inhibitors (AChE-I) to augment available acetylcholine in
      AD, measures of attentional function have not been used to assess the drug
      response. OBJECTIVES: We hypothesized that as cholinergic augmentation impacts
      directly on the attentional system, higher-order measures of visual selective
      attention would be sensitive to effects of treatment using an AChE-I (donepezil
      hydrochloride). We also sought to determine whether these attentional measures
      were more sensitive to treatment than other measures of cognitive function.
      METHODS: Seventeen patients with AD (8 untreated, 9 treated with donepezil) were
      contrasted on performance of a selective cancellation task. Two signal detection
      parameters were used as outcome measures: decision strategy (beta, beta) and
      discriminability (d-prime, d'). Standard screening and cognitive domain measures
      of vigilance, language, memory, and executive function were also contrasted.
      RESULTS: Treated patients judged stimuli more conservatively (p = 0.29) by
      correctly endorsing targets and rejecting false alarms. They also discriminated
      targets from distractors more easily (p = 0.58). The screening and
      neuropsychological measures failed to differentiate the groups. CONCLUSIONS:
      Higher-order attentional measures captured the effects of donepezil treatment in
      small groups of patients with AD. The results suggest that cholinergic
      availability may directly affect the attentional system, and that these selective
      attention measures are sensitive markers to detect treatment response.

PMID- 15852462
TI  - The clinical psychiatry of late life in Britain from 1950 to 1970: an overview.
AB  - BACKGROUND: The psychiatry of old age in Britain can be traced back to the 1940s.
      Provision of services for mentally ill older people, however, did not become
      widespread until the 1970s. METHOD: Survey of archive sources, published work,
      and oral history interviews relating to the development of services for mentally
      ill older people in Britain between 1950 and 1970. RESULTS AND CONCLUSIONS:
      Despite considerable progress in research leading to a firm academic foundation
      for the specialty of old age psychiatry, there was relatively little progress
      made in the coordinated development of services from 1950 to 1970. A new
      generation of old age psychiatrists began to take service delivery issues forward
      at the very end of the 1960s and into the 1970s.

PMID- 15852463
TI  - VITA: subtypes of mild cognitive impairment in a community-based cohort at the
      age of 75 years.
AB  - BACKGROUND: Mild cognitive impairment (MCI) is defined to diagnose prodromal
      dementia and prodromal Alzheimer dementia, in particular. OBJECTIVE: The main aim
      of this study is to identify subtypes of MCI in comparison to the frequency of
      Petersen's MCI-amnestic in an elderly age-cohort. PARTICIPANTS: The study is
      based on the cross sectional data from the Vienna-Transdanube-Aging (VITA) study.
      The data refer to the age cohort of 592 individuals at age 75 to 76 years who
      completed extensive neuropsychological examination. RESULTS: Dementia was present
      in 15 subjects (2.5%, CI: 1.4-4.1). 141 subjects (23.8%, CI: 20.4-27.5) of the
      entire age cohort 75 (n = 592) showed cognitive impairment without dementia
      concerning one or more cognitive functions (1.5 SD paradigm). These subjects were
      assigned to three subtypes of MCI: Selective Memory Impairment: n = 22 (3.7%, CI:
      2.3-5.6), Memory Impairment+Non-Memory Impairment: n = 31 (5.2%, CI: 3.6-7.4) and
      Non-Memory Impairment: n = 88 (14.9%, CI: 12.1-18.0). CONCLUSIONS: The frequency
      of MCI-amnestic, the so-called prestage of AD according to Petersen, was very low
      (0.5%, CI: 0.1-1.5) compared to the estimated incidence rates of AD at this age.
      Established criteria of MCI could be modified in order to include a higher
      percentage of high-risk subjects for later developing Alzheimer dementia.

PMID- 15852464
TI  - Effects of caffeine on prospective duration judgements of various intervals
      depend on task difficulty.
AB  - The effects of caffeine on prospective duration judgements were investigated in
      two double-blind placebo-controlled experiments. After taking either 200 mg of
      caffeine or a placebo, participants performed a task that demanded considerable
      attention, driving a car in a simulator (Experiment 1) or a task that demanded
      relatively little attention, watching a videotaped scene from a driven car
      (Experiment 2). Each participant made duration judgements of three target
      intervals: 15 s, 60 s and 300 s. Actively driving participants in the caffeine
      condition judged it as shorter than did those in the placebo condition. Caffeine
      had no effect on duration judgements following passive viewing. When people must
      perform a relatively difficult task, caffeine causes participants to allocate
      relatively more of their attentional resources to the task and relatively less to
      duration timing. Although caffeine may increase the pacemaker rate of an internal
      clock (via dopamine D(1) agonism), when external events are attention-demanding,
      caffeine mainly influences the relative allocation of attention to external
      events or to time (via dopamine D(2) agonism) in cerebral areas subserving the
      executive control of attention.

PMID- 15852465
TI  - Brain mechanisms of involuntary visuospatial attention: an event-related
      potential study.
AB  - The brain mechanisms mediating visuospatial attention were investigated by
      recording event-related potentials (ERPs) during a line-orientation
      discrimination task. Nonpredictive peripheral cues were used to direct
      participant's attention involuntarily to a spatial location. The earliest
      attentional modulation was observed in the P1 component (peak latency about 130
      ms), with the valid trials eliciting larger P1 than invalid trials. Moreover, the
      attentional modulations on both the amplitude and latency of the P1 and N1
      components had a different pattern as compared to previous studies with voluntary
      attention tasks. In contrast, the earliest visual ERP component, C1 (peak latency
      about 80 ms), was not modulated by attention. Low-resolution brain
      electromagnetic tomography (LORETA) showed that the earliest attentional
      modulation occurred in extrastriate cortex (middle occipital gyrus, BA 19) but
      not in the primary visual cortex. Later attention-related reactivations in the
      primary visual cortex were found at about 110 ms after stimulus onset. The
      results suggest that involuntary as well as voluntary attention modulates visual
      processing at the level of extrastriate cortex; however, at least some different
      processes are involved by involuntary attention compared to voluntary attention.
      In addition, the possible feedback from higher visual cortex to the primary
      visual cortex is faster and occurs earlier in involuntary relative to voluntary
      attention task.

PMID- 15852466
TI  - Brain structures involved in interoceptive awareness and cardioafferent signal
      processing: a dipole source localization study.
AB  - Afferent signals from the body play an important role for emotional and
      motivational aspects of behavior. Nevertheless, little is known about the
      cortical and subcortical structures involved in interoceptive processes.
      Recently, a functional MRI study demonstrated that insula, somatomotor, and
      cingulated cortices are activated when subjects focus attention on their
      heartbeats. Aside from the use of imaging data, cardiac awareness has frequently
      been studied by using the heartbeat-evoked potential (HEP), a brain wave that
      appears contingent on the heartbeat. The present study aimed at localizing
      sources of the HEP. Multichannel EEG was recorded in 44 subjects while they
      performed a heartbeat perception task. This task was used to quantify
      interoceptive awareness and to subdivide the subjects into good and poor
      heartbeat perceivers. Analyses showed highest HEP amplitudes over frontal and
      frontocentral electrode locations in the time range of later than 200 ms after R
      wave onset. By means of a BESA dipole-source-analysis, four sources of the HEP
      were identified which were located in the anterior cingulate, the right insula,
      the prefrontal cortex, and the left secondary somatosensory cortex. Good
      heartbeat perceivers showed both significantly higher HEP amplitudes and higher
      dipole strength than poor heartbeat perceivers in all four cortical sources. We
      conclude that the identified structures are involved in the processing of cardiac
      signals, whereby anterior cingulate and right insula seem to serve as
      interoceptive centers for cardioception.

PMID- 15852467
TI  - Modulation of auditory cortex activation by sound presentation rate and
      attention.
AB  - We studied the effects of sound presentation rate and attention on auditory
      supratemporal cortex (STC) activation in 12 healthy adults using functional
      magnetic resonance imaging (fMRI) at 3 T. The sounds (200 ms in duration) were
      presented at steady rates of 0.5, 1, 1.5, 2.5, or 4 Hz while subjects either had
      to focus their attention to the sounds or ignore the sounds and attend to visual
      stimuli presented with a mean rate of 1 Hz. Consistent with previous
      observations, we found that both increase in stimulation rate and attention to
      sounds enhanced activity in STC bilaterally. Further, we observed larger
      attention effects with higher stimulation rates. This interaction of attention
      and presentation rate has not been reported previously. In conclusion, our
      results show both rate-dependent and attention-related modulations of STC
      indicating that both factors should be controlled, or at least addressed, in fMRI
      studies of auditory processing.

PMID- 15852468
TI  - Spontaneous low-frequency BOLD signal fluctuations: an fMRI investigation of the
      resting-state default mode of brain function hypothesis.
AB  - Recent neuroimaging studies have lead to the proposal that rest is characterized
      by an organized, baseline level of activity, a default mode of brain function
      that is suspended during specific goal-oriented mental activity. Previous studies
      have shown that the primary function subserved by the default mode is that of an
      introspectively oriented, self-referential mode of mental activity. The default
      mode of brain function hypothesis is readdressed from the perspective of the
      presence of low-frequency blood oxygenation level-dependent (BOLD) functional
      magnetic resonance imaging (fMRI) signal changes (0.012-0.1 Hz) in the resting
      brain. The results show that the brain during rest is not tonically active in a
      single mode of brain function. Rather, the findings presented here suggest that
      the brain recurrently toggles between an introspectively oriented mode (default
      mode) and a state-of-mind that tentatively might be interpreted as an
      extrospectively oriented mode that involves a readiness and alertness to changes
      in the external and internal environment.

PMID- 15852469
TI  - The effect of social content on deductive reasoning: an fMRI study.
AB  - Psychological studies of deductive reasoning have shown that subjects'
      performance is affected significantly by the content of the presented stimuli.
      Specifically, subjects find it easier to reason about contexts and situations
      with a social content. In the present study, the effect of content on brain
      activation was investigated with functional magnetic resonance imaging (fMRI)
      while subjects were solving two versions of the Wason selection task, which
      previous behavioral studies have shown to elicit a significant content effect.
      One version described an arbitrary relation between two actions (Descriptive: "If
      someone does ..., then he does ..."), whereas the other described an exchange of
      goods between two persons (Social-Exchange: "If you give me ..., then I give you
      ..."). Random-effect statistical analyses showed that compared to baseline, both
      tasks activated frontal medial cortex and left dorsolateral frontal and parietal
      regions, confirming the major role of the left hemisphere in deductive reasoning.
      In addition, although the two reasoning conditions were identical in logical
      form, the social-exchange task was also associated with right frontal and
      parietal activations, mirroring the left-sided activations common to both
      reasoning tasks. These results suggest that the recruitment of the right
      hemisphere is dependent on the content of the stimuli presented.

PMID- 15852470
TI  - Exploring the unity and diversity of the neural substrates of executive
      functioning.
AB  - Previous studies exploring the neural substrates of executive functioning used
      task-specific analyses, which might not be the most appropriate approach due to
      the difficulty of precisely isolating executive functions. Consequently, the aim
      of this study was to use positron emission tomography (PET) to reexamine by
      conjunction and interaction paradigms the cerebral areas associated with three
      executive processes (updating, shifting, and inhibition). Three conjunction
      analyses allowed us to isolate the cerebral areas common to tasks selected to tap
      into the same executive process. A global conjunction analysis demonstrated that
      foci of activation common to all tasks were observed in the right intraparietal
      sulcus, the left superior parietal gyrus, and at a lower statistical threshold,
      the left lateral prefrontal cortex. These regions thus seem to play a general
      role in executive functioning. The right intraparietal sulcus seems to play a
      role in selective attention to relevant stimuli and in suppression of irrelevant
      information. The left superior parietal region is involved in amodal
      switching/integration processes. One hypothesis regarding the functional role of
      the lateral prefrontal cortex is that monitoring and temporal organization of
      cognitive processes are necessary to carry out ongoing tasks. Finally,
      interaction analyses showed that specific prefrontal cerebral areas were
      associated with each executive process. The results of this neuroimaging study
      are in agreement with cognitive studies demonstrating that executive functioning
      is characterized by both unity and diversity of processes.

PMID- 15852471
TI  - Neural network involved in time perception: an fMRI study comparing long and
      short interval estimation.
AB  - In this study, long ( approximately 1,300 ms) and short duration ( approximately
      450 ms) estimation trials in an event-related functional MRI (fMRI) study were
      contrasted in order to reveal the regions within a time estimation network
      yielding increased activation with the increase of the duration to be estimated.
      In accordance with numerous imaging studies, our results showed that the
      presupplementary motor area (preSMA), the anterior cingulate, the prefrontal and
      parietal cortices, and the basal ganglia were involved in the estimation trials
      whatever the duration to be estimated. Moreover, only a subset of the regions
      within this distributed cortical and subcortical network yielded increased
      activation with increasing time, namely, the preSMA, the anterior cingulate
      cortex, the right inferior frontal gyrus (homolog to Broca's area), the bilateral
      premotor cortex, and the right caudate nucleus. This suggests that these regions
      are directly involved in duration estimation. We propose that the caudate-preSMA
      circuit, the anterior cingulate, and the premotor-inferior frontal regions may
      support a clock mechanism, decision and response-related processes, and active
      maintenance of temporal information, respectively.

PMID- 15852472
TI  - Amplification of IGH/MYC fusion in clinically aggressive IGH/BCL2-positive
      germinal center B-cell lymphomas.
AB  - Activation of an oncogene via its juxtaposition to the IGH locus by a chromosomal
      translocation or, less frequently, by genomic amplification is considered a major
      mechanism of B-cell lymphomagenesis. However, amplification of an IGH/oncogene
      fusion, coined a complicon, is a rare event in human cancers and has been
      associated with poor outcome and resistance to treatment. In this article are
      descriptions of two cases of germinal-center-derived B-cell lymphomas with
      IGH/BCL2 fusion that additionally displayed amplification of an IGH/MYC fusion.
      As shown by fluorescence in situ hybridization, the first case contained a
      IGH/MYC complicon in double minutes, whereas the second case showed a
      BCL2/IGH/MYC complicon on a der(8)t(8;14)t(14;18). Additional molecular
      cytogenetic and mutation analyses revealed that the first case also contained a
      chromosomal translocation affecting the BCL6 oncogene and a biallelic
      inactivation of TP53. The second case harbored a duplication of REL and acquired
      a translocation affecting IGL and a biallelic inactivation of TP53 during
      progression. Complicons affecting Igh/Myc have been reported previously in
      lymphomas of mouse models simultaneously deficient in Tp53 and in genes of the
      nonhomologous end-joining DNA repair pathway. To the best of our knowledge, this
      is the first time that IGH/MYC complicons have been reported in human lymphomas.
      Our findings imply that the two mechanisms resulting in MYC deregulation, that
      is, translocation and amplification, can occur simultaneously.

PMID- 15852473
TI  - Somatotopic organization of the corticospinal tract in the human brainstem: a MRI
      based mapping analysis.
AB  - To investigate the incompletely understood somatotopical organization of the
      corticospinal tract in the human brainstem, we performed a voxel-based
      statistical analysis of standardized magnetic resonance scans of 41 prospectively
      recruited patients with pyramidal tract dysfunction caused by acute brainstem
      infarction. Motor hemiparesis was rated clinically and by the investigation of
      motor evoked potentials to arms and legs. Infarction affected the pons in 85% of
      cases. We found the greatest level of significance of affected brainstem areas
      between the pontomesencephalic junction and the mid pons. Lesion location was
      significantly more dorsal in patients with hemiparesis affecting more proximal
      muscles and was significantly more ventral in patients with predominantly distal
      limb paresis. Comparison of magnetic resonance lesion from patients with paresis
      predominantly affecting arm or leg did not show significant topographical
      differences. We conclude that a topographical arm/leg distribution of
      corticospinal fibers is abruptly broken down as the descending corticospinal
      tract traverses the pons. Corticospinal fibers, however, follow a somatotopical
      order in the pons with fibers controlling proximal muscles being located close to
      the reticular formation in the dorsal pontine base, and thus more dorsal than the
      fibers controlling further distal muscle groups.

PMID- 15852474
TI  - Hypoparathyroidism-retardation-dysmorphism (HRD) syndrome in triplets.
AB  - We report female triplets with the clinical and biochemical manifestations of
      hypoparatyroidism-retardation-dysmorphism (HRD) syndrome also known as Sanjad
      Sakati syndrome. They were born at 35 weeks gestation after assisted pregnancy
      (in vitro fertilization). The parents are first degree cousins from Saudi Arabia.

PMID- 15852475
TI  - Other tumors in Sotos syndrome.

PMID- 15852476
TI  - Novel autosomal recessive progressive hyperpigmentation syndrome.
AB  - We present a family of Iraqui origin with three siblings affected by a novel type
      of progressive hyperpigmentation syndrome. The generalized initially diffuse,
      later disseminated hyperpigmentation started in early infancy and increased
      during childhood. It also affected palms and soles, and the face but spared the
      cheeks. Additional features were dry, itchy and sunlight sensitive skin,
      dystrophy of toe nails, hair loss, and myopia, but normal sweat glands. Light and
      electron microscopy showed signs of pigment incontinence and compound melanosomes
      as well as fibrillar bodies. The occurrence of this entity in affected siblings
      from a consanguineous mating suggests autosomal recessive inheritance. Extensive
      review of the literature showed no previous report with this distinct combination
      of clinical and microscopic findings.

PMID- 15852477
TI  - Tumor necrosis factor-alpha inhibits seizures in mice via p75 receptors.
AB  - Brain inflammatory reactions have been described in various neurological
      disorders, including epilepsy. Although there is clear evidence that cytokines
      affect neuroglial functions and blood-brain barrier permeability, scarce
      information is available on the functional consequences of brain inflammation on
      seizures. We studied the role of tumor necrosis factor-alpha (TNF)-alpha and its
      p55 and p75 receptors in seizure modulation. We found that intrahippocampal
      injection of murine recombinant TNF-alpha potently inhibits seizure in mice while
      human recombinant TNF-alpha, which shows strong specificity for mouse p55
      receptors, was ineffective. p75 receptors were detected in mouse hippocampal
      neurons, whereas p55 receptors were absent. Transgenic mice with a perturbed TNF
      alpha system showed profound alterations in seizure susceptibility: astrocytic
      overexpression of TNF-alpha was associated with reduced seizures, whereas mice
      lacking TNF-alpha p75 or both p55 and p75, receptors showed prolonged seizures.
      Mice deficient in p55 receptor only showed reduced seizures; and both p75 and TNF
      receptor-associated factor 2 protein levels were upregulated in their hippocampi.
      Our findings show that increased brain levels of TNF-alpha result in significant
      inhibition of seizures in mice, and this action is mediated by neuronal p75
      receptors. This evidence highlights a novel function of TNF-alpha in brain and
      indicates a new system for anticonvulsive intervention.

PMID- 15852478
TI  - Highly active antiretroviral therapy and human immunodeficiency virus
      encephalitis.
AB  - The ability of highly active antiretroviral therapy (HAART) to prevent the onset
      of HIV-associated dementia and to prevent or reduce the neuropathological
      features of HIV encephalitis (HIVE) remains unclear. Using a severe combined
      immunodeficient (SCID) mouse model of HIVE, we determined the effects of regular
      HAART treatment on HIVE. Before studying HAART in infected SCID mice,
      nonmanipulated SCID mice were treated with a single injection of the HAART
      cocktail (consisting of zidovudine, lamivudine, and indinavir) to determine
      optimum dosage and sampling time and to measure antiretroviral levels in the
      brain. After these preliminary studies, SCID mice that were inoculated with
      either HIV-infected or uninfected human monocytes were given intraperitoneal (IP)
      injections of HAART three times daily over a 1- and 2-week period. All three
      drugs were detected in the brain using a novel drug extraction technique and a
      modified high-performance liquid chromatography method. HAART significantly
      decreased the amount of astrogliosis and viral load in treated mice compared with
      mice that received vehicle injections. These studies offer insight into the
      ability of HAART to treat HIV infection of the brain.

PMID- 15852480
TI  - Drawing on mind's canvas: differences in cortical integration patterns between
      artists and non-artists.
AB  - Our primary question was to learn whether mentally composing drawings of their
      own choice produce different brain electric features in artists and laymen. To
      this purpose, we studied multichannel electroencephalograph (EEG) signals from
      two broad groups (all participants were females): artists (professionally trained
      in visual arts) and non-artists (without any training in art). To assess the
      underlying synchronization, which is assumed to be the platform for general
      cognitive integration between different cortical regions, three measures inspired
      by nonlinear dynamical system theory were applied as follows: (1) index based on
      generalized synchronization; (2) index based on mean phase coherence; and (3)
      index of phase synchrony based on entropy. Results consistent over all three
      measures were as follows: comparing the tasks to rest, the artists showed
      significantly stronger short- and long-range delta band synchronization, whereas
      the non-artists showed enhancement in short-range beta and gamma band
      synchronization primarily in frontal regions; comparing the two groups during the
      tasks, the artists showed significantly stronger delta band synchronization and
      alpha band desynchronization than did the non-artists. Strong right hemispheric
      dominance in terms of synchronization was found in the artists. In artists, the
      higher synchrony in the low-frequency band is possibly due to the involvement of
      a more advanced long-term visual art memory and to extensive top-down processing.
      The results demonstrate that in artists, patterns of functional cooperation
      between cortical regions during mental creation of drawings were significantly
      different from those in non-artists.

PMID- 15852479
TI  - Use of MLL/GRAF fusion mRNA for measurement of minimal residual disease during
      chemotherapy in an infant with acute monoblastic leukemia (AML-M5).

PMID- 15852481
TI  - Progressive neuronal degeneration of childhood: prenatal diagnosis by MRI.
AB  - We report two cases in the same family of progressive neuronal degeneration of
      childhood--Alpers syndrome--with prenatal MRI findings in one case. The first
      infant presented at birth with severe microcephaly, then rapidly evolved to
      progressive encephalopathy with refractory epilepsy, leading to death at 10
      months. Biochemical investigations including liver function tests were normal. CT
      and MRI showed severe diffuse brain atrophy. The diagnosis of progressive
      neuronal degeneration of childhood was made on the clinical and imaging data. The
      second pregnancy was marked by gradual decrease of fetal cerebral biometry and a
      prenatal MRI performed at 32 weeks showed diffuse cortical atrophy, as observed
      in the sibling. The infant died at 5 months. Neuropathological findings were
      consistent with Alpers syndrome.

PMID- 15852482
TI  - Antifungal activity of steroidal glycosides from Yucca gloriosa L.
AB  - The antifungal activity of a crude steroidal glycoside extract from Yucca
      gloriosa flowers, named alexin, was investigated in vitro against a panel of
      human pathogenic fungi, yeasts as well as dermatophytes and filamentous species.
      The minimal inhibitory concentration (MIC) was determined by an agar dilution
      method. Alexin had a broad spectrum of antifungal activity, found to reside
      entirely in the spirostanoid fraction. The major tigogenyl glycosides,
      yuccaloeside B and yuccaloeside C, exhibited MICs between 0.39 and 6.25
      microg[sol ]mL for all the tested yeast strains except for two (C. lusitaniae and
      C. kefyr). They were also active against several clinical Candida isolates known
      to be resistant to the usual antifungal agents. The MICs for the dermatophytes
      were between 0.78 and 12.5 microg[sol ]mL. The most sensitive filamentous species
      was A. fumigatus (MIC = 1.56 microg[sol ]mL). For most of the strains, the MICs
      of both glycosides were similar to those of the reference antifungal agent.

PMID- 15852483
TI  - Evaluation of antiprotozoal and plasmodial enoyl-ACP reductase inhibition
      potential of turkish medicinal plants.
AB  - A total of 58 extracts of different polarity were prepared from various organs of
      16 species of Turkish plants and screened for their antitrypanosomal,
      antileishmanial and antiplasmodial activities. No significant activity was
      observed against Trypanosoma cruzi, whereas many extracts showed appreciable
      trypanocidal potential against T. brucei rhodesiense, with the CHCl(3)-soluble
      portion of Phlomis kurdica being the most active (IC(50) 2.7 microg[sol ]mL).
      Almost all extracts, particularly the CHCl(3) phases, exhibited growth inhibition
      activity against Leishmania donovani amastigotes. The CHCl(3)-solubles of Putoria
      calabrica roots (IC(50) 1.9 microg[sol ]mL), Wendlandia ligustroides leaves
      (IC(50) 2.1 microg[sol ]mL) and Rhododendron luteum leaves (IC(50) 2.3 microg[sol
      ]mL) displayed the highest leishmanicidal potential. The majority of the extracts
      also possessed antiplasmodial activity against the multi-drug resistant K1
      Plasmodium falciparum strain. The most potent antiplasmodial activity was
      observed with the CHCl(3) extracts of Phlomis kurdica (IC(50) 1.5 microg[sol
      ]mL), P. leucophracta (IC(50) 1.6 microg[sol ]mL), Scrophularia cryptophila
      (IC(50) 1.8 microg[sol ]mL), Morina persica (IC(50) 1.9 microg[sol ]mL) and the
      aqueous root extract of Asperula nitida subsp. subcapitellata (IC(50) 1.6
      microg[sol ]mL). Twenty-one extracts with significant antimalarial activity
      (IC(50) < 5 microg[sol ]mL) were also tested for their ability to inhibit the
      purified enoyl-ACP reductase (FabI), a crucial enzyme in the fatty acid
      biosynthesis of P. falciparum. The CHCl(3) extract of Rhododendron ungernii
      leaves (IC(50) 10 microg[sol ]mL) and the H(2)O-soluble portion of Rhododendron
      smirnovii leaves (IC(50) 0.4 microg[sol ]mL) strongly inhibited the FabI enzyme.
      The preliminary data indicate that some (poly)phenolic compounds are responsible
      for the FabI inhibition potential of these extracts. The presented work reports
      for the first time the antiprotozoal activity of nine different genera as well as
      a target specific antimalarial screening for the identification of P. falciparum
      FabI inhibitors from medicinal plant extracts.

PMID- 15852484
TI  - Anorectic and behavioural effects of chronic Cissampelos sympodialis treatment in
      female and male rats.
AB  - Male and female rats were treated daily for 13 weeks with an ethanol extract of
      Cissampelos sympodialis leaves (9, 45 and 225 mg[sol ]kg). The food consumption,
      body weight and behavioural effects in the open-field test were evaluated by
      weekly monitoring. The results showed that the extract chronic treatment in
      female rats (45 and 225 mg[sol ]kg) reduced significantly the food intake and the
      body weight, and produced several alterations in the open-field test. These
      findings indicate that repeated oral administration of the extract may produce a
      sex-dependent difference in anoretic and behavioural effects.

PMID- 15852486
TI  - Protective effect of Sargassum polycystum (brown alga) against acetaminophen
      induced lipid peroxidation in rats.
AB  - Lipid peroxidation is believed to play an important role in the pathogenesis of
      several diseases, such as cancer, diabetic mellitus and liver injury. Aqueous and
      ethanol extracts of Sargassum polycystum C. Agardh (Phaeophyta) were screened for
      their protective effects against acetaminophen (ACP; Paracetamol)-induced lipid
      peroxidation in rats. A single dose of acetaminophen significantly elevated the
      levels of lipid peroxides (LPO) with decreased levels of free radical scavenger
      enzymes (SOD, CAT, GSH, GPx, GST) in liver homogenate. The oral pretreatment of
      rats with ethanol and aqueous extracts of Sargassum polycystum C. Agardh (100 mg,
      200 mg[sol ]kg body wt[sol ]day respectively, for a period of 15 days)
      significantly reduced the acetaminophen-induced oxidative stress in rats. The
      animals treated with the ethanol and aqueous extracts alone did not show any
      toxicity on liver tissue. This observation shows that the seaweed crude extracts
      probably acted to protect against acetaminophen-induced lipid peroxidation
      through their free radical scavenging property.

PMID- 15852485
TI  - Cytotoxic constituents of the twigs of Simarouba glauca collected from a plot in
      Southern Florida.
AB  - Activity-guided fractionation of a chloroform-soluble extract of Simarouba glauca
      twigs collected from a plot in southern Florida, and monitored with a human
      epidermoid (KB) tumor cell line, afforded six canthin-6-one type alkaloid
      derivatives, canthin-6-one (1), 2-methoxycanthin-6-one (2), 9-methoxycanthin-6
      one (3), 2-hydroxycanthin-6-one (4), 4,5-dimethoxycanthin-6-one (5) and 4,5
      dihydroxycanthin-6-one (6), a limonoid, melianodiol (7), an acyclic squalene-type
      triterpenoid, 14-deacetyleurylene (8), two coumarins, scopoletin (9) and fraxidin
      (10), and two triglycerides, triolein (11) and trilinolein (12). Among these
      isolates, compounds 1-4, 7 and 8 exhibited cytotoxic activity against several
      human cancer cell lines. 14-Deacetyleurylene (8) was selectively active against
      the Lu1 human lung cancer cell line, but was inactive in an in vivo hollow fiber
      assay using this same cell type.

PMID- 15852487
TI  - Ipriflavone modulates IGF-I but is unable to restore bone in rats.
AB  - Previously it has been reported that ipriflavone can prevent bone loss in ovarian
      hormone deficient rats. The present study evaluated whether ipriflavone was able
      to restore bone mass in osteopenic ovariectomized rats. Seventy-two, 90 day-old
      Sprague-Dawley rats were divided into six groups (sham two groups; ovariectomized
      four groups). Thirty-five days from the date of surgery, one sham and one ovx
      group were killed to verify the occurrence of bone loss. The remaining four
      groups were sham, ovx, ovx + ipriflavone (100 mg[sol ]kg body weight per day), or
      ovx + 17beta-estradiol (10 microg[sol ]kg body weight daily) for a period of 65
      days. Ipriflavone was ineffective in restoring bone density and unlike estrogen
      did not prevent bone resorption as evidenced by increased (p < 0.05) urinary
      excretion of hydroxyproline and serum tartrate-resistant acid phosphatase
      activity. Ipriflavone increased (p < 0.05) the expression of IGF-I in the femur.
      These observations suggest that higher doses of ipriflavone or longer-term
      studies may be necessary to restore bone mass.

PMID- 15852488
TI  - Lignans from Acanthopanax chiisanensis having an inhibitory activity on
      prostaglandin E2 production.
AB  - The chloroform and the ethyl acetate fractions from the roots of Acanthopanax
      chiisanensis exhibited the significant inhibition of TPA-induced prostaglandin
      E(2) (PGE(2)) production in rat peritoneal macrophages. Five lignans were
      isolated from the chloroform fraction and their structures were elucidated as l
      sesamin, helioxanthin, savinin, taiwanin C, and 3-(3,4-dimethoxybenzyl)-2-(3,4
      methylenedioxybenzyl)butyrolactone. Among the lignans tested, taiwanin C showed
      the most potent inhibitory activity (IC(50) = 0.12 microM) on PGE(2) production
      with the relative order of potency, taiwanin C >> 3-(3,4-dimethoxybenzyl)-2-(3,4
      methylenedioxybenzyl)butyrolactone > savinin = helioxanthin. l-Sesamin showed no
      inhibitory activity at 30 microM.

PMID- 15852489
TI  - In Vitro culture studies of FlorEssence on human tumor cell lines.
AB  - FlorEssence (FE) is an herbal tea widely used by patients to treat chronic
      conditions in North America, particularly cancer patients during chemo- and
      radiation therapy. Although individual components of FE have antioxidant,
      antiestrogenic, immunostimulant and antitumor properties, in vitro evidence of
      anticancer activity for the herbal tea itself is still lacking. We studied the
      antiproliferative effect of FE on MCF7 and MDA-MB-468 human breast cancer, and
      Jurkat and K562 leukemia cell lines. We found that FE significantly inhibited the
      proliferation of both breast and leukemia cells in vitro only at high
      concentrations, with 50% inhibition of MDA-MB-468 cells at about 1[sol ]20
      dilution, Jurkat cells at about 1[sol ]10 dilution and MCF7 and K562 cells at
      less than 1[sol ]10 dilution. Flow cytometry analysis showed that treatment with
      a high concentration of FE induced G2[sol ]M arrest in MCF7 and Jurkat cells,
      with also an increased SubG0[sol ]G1 fraction in MCF7 cells. MDA-MB-468 cells
      showed a significantly increased Sub G0[sol ]G1 fraction after treatment with
      1[sol ]10 dilution of FE while the cell cycle of K562 was unaffected. When MCF7
      and MDA-MB-468 breast cancer cells were treated with a combination of FE with
      either paclitaxel or cisplatin, results showed that only the combination of 1[sol
      ]20 dilution of FE with 0.5 microM cisplatin resulted in a small but
      significantly higher MCF7 cell survival than 0.5 microM cisplatin treatment
      alone. FE at 1[sol ]20 and 1[sol ]50 dilutions did not affect the
      antiproliferative properties of these two commonly used chemotherapeutic agents.
      The results suggest that FE at high concentrations show differential inhibitory
      effect on different human cancer cell lines. Further studies are needed to assess
      the biological activities of FE.

PMID- 15852490
TI  - Siberian ginseng reduces infarct volume in transient focal cerebral ischaemia in
      Sprague-Dawley rats.
AB  - Siberian ginseng, the root and stem bark of Acanthopanax senticosus Harms, has
      been used as a tonic and adaptogen to strengthen qi in traditional Korean
      medicine. The neuroprotective effects of water extracts of A. senticosus (ASW)
      were investigated in transient middle cerebral artery occlusion (MCAo, 90 min
      occlusion, 24 h reperfusion) of Sprague-Dawley rats. The infarct volume was
      significantly reduced by 36.6% after the peritoneal injection of ASW (100 mg[sol
      ]kg) compared with the control. In the immunohistochemical study, ASW markedly
      inhibited both cyclooxygenase-2 and OX-42 expressions in the penumbral region at
      24 h after MCAo. These results suggest that A. senticosus has a neuroprotective
      effect by inhibiting inflammation and microglial activation in brain ischaemia.

PMID- 15852491
TI  - Hepatoprotective activity of aqueous-methanol extract of Artemisia vulgaris.
AB  - The effect of a crude extract of the aerial parts of Artemisia vulgaris (Av.Cr)
      was investigated against D-galactosamine (D-GalN) and lipopolysaccharide (LPS)
      induced hepatitis in mice. Co-administration of D-GalN (700 mg[sol ]kg) and LPS
      (1 microg[sol ]kg) significantly (p < 0.05) raised the plasma levels of alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) in mice in the toxin
      group compared with the values in the control group. Pre-treatment of mice with
      different doses of Av.Cr (150-600 mg[sol ]kg) significantly (p < 0.05) reduced
      the toxin-induced rise in plasma ALT and AST. The hepatoprotective effect was
      further verified by histopathology of the liver, which showed improved
      architecture, absence of parenchyma congestion, decreased cellular swelling and
      apoptotic cells, compared with the findings in the toxin group of animals. These
      findings scientifically validated the traditional use of Artemisia vulgaris for
      various liver disorders.

PMID- 15852492
TI  - Crocus sativus L. in the treatment of mild to moderate depression: a double
      blind, randomized and placebo-controlled trial.
AB  - Depression is a serious disorder in today's society, with estimates of lifetime
      prevalence as high as 21% of the general population in some developed countries.
      As a therapeutic plant, saffron is considered excellent for stomach ailments and
      as an antispasmodic, to help digestion and to increase appetite. It is also used
      for depression in Persian traditional medicine. Our objective was to assess the
      efficacy of the stigmas of Crocus sativus (saffron) in the treatment of mild to
      moderate depression in a 6-week double-blind, placebo-controlled and randomized
      trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of
      Mental Disorders, 4th edition for major depression based on the structured
      clinical interview for DSM IV participated in the trial. Patients had a baseline
      Hamilton rating scale for depression score of at least 18. In this double-blind,
      placebo-controlled, single-centre and randomized trial, patients were randomly
      assigned to receive a capsule of saffron 30 mg[sol ]day (BD) (Group 1) or a
      capsule of placebo (BD) (Group 2) for a 6-week study. At 6 weeks, Crocus sativus
      produced a significantly better outcome on the Hamilton depression rating scale
      than the placebo (d.f. = 1, F = 18.89, p < 0.001). There were no significant
      differences in the two groups in terms of the observed side effects. The results
      of this study indicate the efficacy of Crocus sativus in the treatment of mild to
      moderate depression. A large-scale trial is justified.

PMID- 15852493
TI  - Antiproliferative effects of daucane esters from Ferula communis and F. arrigonii
      on human colon cancer cell lines.
AB  - Certain jaesekanadiol p-hydroxy- and p-methoxybenzoates - typical of Ferula
      communis and Ferula arrigonii sardinian plants - show antiproliferative activity
      on human colon cancer less. The inhibitory doses 50%, calculated after 72 h of
      treatment, revealed that the antiproliferative capacity of the compounds was in
      the following descending order: ferutinin > 2alpha-OH-ferutidin > ferutidin >
      siol anisate > lapiferin > jaeskeanadiol. Evidence is presented that interaction
      with type II estrogen-binding sites (EBS) underlies this activity.

PMID- 15852494
TI  - Ritual use of plants with possible action on the central nervous system by the
      Kraho Indians, Brazil.
AB  - The aim of the present study was to document the use of plants, probably acting
      on the central nervous system (CNS), in rituals carried out by the Kraho Indians,
      who occupy the cerrado biome in the central region of Brazil. The 2 years of
      fieldwork were guided by methods of anthropology and botany. The local shamans
      have indicated 286 formulas, consisting of 138 plant species in 50 uses that
      could be associated with some type of action on the CNS; of which 98 formulas, 87
      plants and 25 uses, appear to involve psychoactive properties, such as: 'to get
      slow', 'stimulant effect', 'to calm down', 'to enhance memory', 'to reduce
      anxiety' and 'to induce sleep'. Phytochemical and pharmacological literature data
      were queried to establish any correlation between indigenous knowledge and
      scientific indications, for each one of the 138 plant species. Studies were
      available for 11 of these plants; and for two of them, scientific data coincided
      with indigenous information.

PMID- 15852495
TI  - Radical scavenging activity of Alkanna tinctoria root extracts and their main
      constituents, hydroxynaphthoquinones.
AB  - Alkannin and shikonin (A[sol ]S) are pharmaceutical substances with a wide
      spectrum of biological properties. Radical scavenging activity is involved in
      aging processes, antiinssammatory, anticancer and wound healing activities.
      Hence, in the present study the DPPH radical scavenging activity of alkannin and
      shikonin, both monomeric and oligomeric, and extracts of Alkanna tinctoria roots
      were studied and a structure-activity relationship was approximated. It was shown
      that both monomeric and oligomeric alkannin and shikonin and also A[sol ]S esters
      exhibited extremely high radical scavenging activity. The presence of the
      naphthoquinone moiety seems to be essential for that activity, while the side
      chain of A[sol ]S possibly plays a minor role. Esterification of A[sol ]S on the
      side chain hydroxyl group does not affect radical scavenging activity. Organic
      solvents and olive oil (extracted at room temperature) extracts of Alkanna
      tinctoria roots, which contain as active ingredients A[sol ]S esters, exhibited
      very good antiradical activity. Alkannin and shikonin and their esters and also
      extracts of Alkanna tinctoria roots could be used promisingly in pharmaceutical
      and cosmetic preparations for their radical scavenging activity and probably for
      their antiaging activity.

PMID- 15852496
TI  - Lipoxygenase inhibitors from natural plant sources. Part 1: Medicinal plants with
      inhibitory activity on arachidonate 5-lipoxygenase and 5-lipoxygenase[sol
      ]cyclooxygenase.
AB  - Arachidonate 5-lipoxygenase is the key enzyme in leukotriene biosynthesis and
      catalyses the initial steps in the conversion of arachidonic acid to biologically
      active leukotrienes. Leukotrienes are considered as potent mediators of
      inflammatory and allergic reactions and regarding their pro-inflammatory
      properties the inhibition of 5-lipoxygenase pathway is considered to be
      interesting in the treatment of a variety of inflammatory diseases. Besides 5
      lipoxygenase inhibitors, drugs able to block the 5-lipoxygenase as well as the
      cyclooxygenase metabolic pathway are also of therapeutic value. A potential
      source for new 5-lipoxygenase inhibitors is undoubtedly provided by the abundance
      of medicinal plants used in traditional medicine. The present review article
      reports the results from a comprehensive literature search of plants that have
      been tested for 5-lipoxygenase inhibitory activity over the past 15 years. The
      obtained information is summarized in a tabular format and promising plant
      species and chemical classes of compounds are presented. Relevant in vitro tests
      are also described in this article.

PMID- 15852497
TI  - Hypoglycaemic activity of Retama raetam in rats.
AB  - The purpose of this study was to determine the underlying mechanism of the
      hypoglycaemic activity of an aqueous extract perfusion of Retama raetam (RR) in
      normal and streptozotocin-induced diabetic rats. The aqueous extract was
      administered intravenously and the blood glucose changes were determined within 4
      h after starting the treatment. Plasma insulin concentrations and glycosuria were
      determined. The aqueous RR extract at a dose of 10 mg[sol ]kg[sol ]h produced a
      significant decrease in blood glucose levels in normal rats (p < 0.001) and an
      even more marked decrease in diabetic rats (p < 0.001). This hypoglycaemic effect
      might be due to an extra-pancreatic action of the aqueous extract of RR, since
      the basal plasma insulin concentrations were unchanged after RR treatment. A
      potent increase of glycosuria was observed both in normal and diabetic rats (p <
      0.001). It is concluded that an aqueous extract perfusion of RR caused a potent
      inhibition of renal glucose reabsorption. This renal effect is at least one
      mechanism to explain the observed hypoglycaemic activity of this plant in normal
      and diabetic rats.

PMID- 15852498
TI  - Adenomas and follicular carcinomas of the thyroid display two major patterns of
      chromosomal changes.
AB  - It was recently shown by flow and static cytometry that a large sub-group of
      follicular adenomas of the thyroid--fetal/embryonal adenomas--display an
      aneuploid phenotype. It was also shown that thyroid lesions with a DNA content
      within the triploid range were either fetal adenomas or follicular carcinomas
      with a fetal adenoma growth pattern. Follicular tumours with growth patterns
      other than the so-called fetal adenoma-like pattern were usually diploid or near
      diploid. In an attempt to clarify the pattern of chromosomal imbalances in
      follicular tumours, comparative genomic hybridization (CGH) analysis was
      performed in a series of 18 follicular neoplasms (ten fetal/embryonal and four
      common follicular adenomas and four minimally invasive follicular carcinomas).
      For each tumour, the DNA content was determined by flow cytometry and, in some
      cases, also by static cytometry. Finally, the copy number of selected chromosomes
      was determined by interphase fluorescence in situ hybridization (FISH) using
      centromere probes. With the exception of the single diploid fetal adenoma, all
      fetal adenomas displayed several DNA copy number changes, with frequent gains of
      several chromosomes, which were found to be either tetrasomic or trisomic by
      FISH. This genetic pattern was also present in the single case of follicular
      carcinoma with aneuploidy and fetal adenoma-like growth pattern. Follicular
      adenomas other than fetal adenomas, and the remaining follicular carcinomas,
      showed more losses than gains of chromosomes. These results suggest that
      follicular tumourigenesis may follow at least two pathways: one characterized by
      prominent aneuploidy and numerous gains, in which the tumours display a fetal
      adenoma-like growth pattern; and another accompanied by less obvious aneuploidy
      or even quasi-diploidy and dominant chromosome losses, in which the tumours
      display a common follicular architecture.

PMID- 15852499
TI  - E-cadherin-dependent adhesion of dendritic and Langerhans cells to keratinocytes
      is defective in cervical human papillomavirus-associated (pre)neoplastic lesions.
AB  - Although human papillomavirus (HPV) DNA is detected in the majority of squamous
      intraepithelial lesions (SILs) and squamous cell carcinomas (SCCs) of the uterine
      cervix, the persistence and progression of cervical lesions suggest that viral
      antigens are not adequately presented to the immune system. This hypothesis is
      reinforced by the observation that most SILs show quantitative and functional
      alterations of Langerhans cells (LCs). The aim of this study was to determine
      whether modulation of E-cadherin-mediated homophilic and heterotypic interactions
      between keratinocytes and LCs is involved in these abnormalities of LCs in
      (pre)neoplastic cervical epithelium. Cell membrane expression of E-cadherin and
      the density of CD1a+ LCs were low in the epithelium of SILs and SCC biopsy
      specimens, compared with normal exocervical epithelium. Dendritic cells (DCs) and
      LCs generated in vitro were randomly distributed throughout the full thickness of
      organotypic cultures of E-cadherin- HPV-transformed cells. In contrast, these
      cells rapidly adhered to the keratinocyte cell layers when HPV-transformed cells
      transfected with E-cadherin were used. These data suggest that the E-cadherin
      mediated contact between keratinocytes and LCs is potentially important for
      initiating or maintaining the immune response during chronic HPV infection.

PMID- 15852500
TI  - Minimum redundancy feature selection from microarray gene expression data.
AB  - How to selecting a small subset out of the thousands of genes in microarray data
      is important for accurate classification of phenotypes. Widely used methods
      typically rank genes according to their differential expressions among phenotypes
      and pick the top-ranked genes. We observe that feature sets so obtained have
      certain redundancy and study methods to minimize it. We propose a minimum
      redundancy - maximum relevance (MRMR) feature selection framework. Genes selected
      via MRMR provide a more balanced coverage of the space and capture broader
      characteristics of phenotypes. They lead to significantly improved class
      predictions in extensive experiments on 6 gene expression data sets: NCI,
      Lymphoma, Lung, Child Leukemia, Leukemia, and Colon. Improvements are observed
      consistently among 4 classification methods: Naive Bayes, Linear discriminant
      analysis, Logistic regression, and Support vector machines. SUPPLIMENTARY: The
      top 60 MRMR genes for each of the datasets are listed in
      http://crd.lbl.gov/~cding/MRMR/. More information related to MRMR methods can be
      found at http://www.hpeng.net/.

PMID- 15852501
TI  - Complexity and approximability of double digest.
AB  - We revisit the DOUBLE DIGEST problem, which occurs in sequencing of large DNA
      strings and consists of reconstructing the relative positions of cut sites from
      two different enzymes. We first show that DOUBLE DIGEST is strongly NP-complete,
      improving upon previous results that only showed weak NP-completeness. Even the
      (experimentally more meaningful) variation in which we disallow coincident cut
      sites turns out to be strongly NP-complete. In the second part, we model errors
      in data as they occur in real-life experiments: we propose several optimization
      variations of DOUBLE DIGEST that model partial cleavage errors. We then show that
      most of these variations are hard to approximate. In the third part, we
      investigate variations with the additional restriction that coincident cut sites
      are disallowed, and we show that it is NP-hard to even find feasible solutions in
      this case, thus making it impossible to guarantee any approximation ratio at all.

PMID- 15852502
TI  - Systematic variation normalization in microarray data to get gene expression
      comparison unbiased.
AB  - Normalization removes or minimizes the biases of systematic variation that exists
      in experimental data sets. This study presents a systematic variation
      normalization (SVN) procedure for removing systematic variation in two channel
      microarray gene expression data. Based on an analysis of how systematic variation
      contributes to variability in microarray data sets, our normalization procedure
      includes background subtraction determined from the distribution of pixel
      intensity values from each data acquisition channel and log conversion, linear or
      non-linear regression, restoration or transformation, and multiarray
      normalization. In the case when a non-linear regression is required, an empirical
      polynomial approximation approach is used. Either the high terminated points or
      their averaged values in the distributions of the pixel intensity values observed
      in control channels may be used for rescaling multiarray datasets. These pre
      processing steps remove systematic variation in the data attributable to
      variability in microarray slides, assay-batches, the array process, or
      experimenters. Biologically meaningful comparisons of gene expression patterns
      between control and test channels or among multiple arrays are therefore unbiased
      using normalized but not unnormalized datasets.

PMID- 15852503
TI  - Multiple sequence alignment using an exhaustive and greedy algorithm.
AB  - We describe an exhaustive and greedy algorithm for improving the accuracy of
      multiple sequence alignment. A simple progressive alignment approach is employed
      to provide initial alignments. The initial alignment is then iteratively
      optimized against an objective function. For any working alignment, the
      optimization involves three operations: insertions, deletions and shuffles of
      gaps. The optimization is exhaustive since the algorithm applies the above
      operations to all eligible positions of an alignment. It is also greedy since
      only the operation that gives the best improving objective score will be
      accepted. The algorithms have been implemented in the EGMA (Exhaustive and Greedy
      Multiple Alignment) package using Java programming language, and have been
      evaluated using the BAliBASE benchmark alignment database. Although EGMA is not
      guaranteed to produce globally optimized alignment, the tests indicate that EGMA
      is able to build alignments with high quality consistently, compared with other
      commonly used iterative and non-iterative alignment programs. It is also useful
      for refining multiple alignments obtained by other methods.

PMID- 15852504
TI  - An ancova approach to normalize microarray data, and its performance to existing
      methods.
AB  - A microarray experiment includes many steps, and each one of them may include
      systematic variations. To have a sound analysis, the systematic bias must be
      identified and removed prior to the data being analyzed. Based on the M-A
      dependency observed by Dudoit et al. (2002), we suggest that, instead of using
      the lowess normalization, a new normalization method called ANCOVA be used for
      dealing with genes with replicates. Simulation studies have shown that the
      performance of the suggested ANCOVA method is superior to any of the available
      approaches with regards to the Fisher's Z score and concordance rate. We used a
      microarray data from bladder cancer to illustrate the application of our
      approach. The edge the ANCOVA method has over the existing normalization
      approaches is further confirmed through real-time PCR.

PMID- 15852505
TI  - An optimization method for the identification of minimal sets of discriminating
      gene markers: application to cultivar identification in wheat.
AB  - A potentially large number of molecular markers are available for identifying
      genotypes in various species. For wheat, cultivar identity is an important
      determinant for end-use segregation and for payment of end-point royalties and
      grower premiums. A number of dominant DNA markers, that give either a positive or
      negative response, have been developed previously for wheat cultivar
      identification. This paper gives a method for identifying minimal marker sets for
      a given cultivar group, for example those grown in a specific geographical zone.
      It is based on an integer linear programming formulation of the problem, and can
      find all minimal marker sets for the group if required. The paper then describes
      the production of two software packages, GGDS and GGIP, that incorporate this
      methodology. Various practical issues are also discussed. These packages enable
      the rapid selection of minimal marker sets for the efficient discrimination of
      any sample set where the marker responses of the samples are known. They are
      already being used by the Australian wheat industry.

PMID- 15852506
TI  - Clustering and re-clustering for pattern discovery in gene expression data.
AB  - The combined interpretation of gene expression data and gene sequences is
      important for the investigation of the intricate relationships of gene expression
      at the transcription level. The expression data produced by microarray
      hybridization experiments can lead to the identification of clusters of co
      expressed genes that are likely co-regulated by the same regulatory mechanisms.
      By analyzing the promoter regions of co-expressed genes, the common regulatory
      patterns characterized by transcription factor binding sites can be revealed.
      Many clustering algorithms have been used to uncover inherent clusters in gene
      expression data. In this paper, based on experiments using simulated and real
      data, we show that the performance of these algorithms could be further improved.
      For the clustering of expression data typically characterized by a lot of noise,
      we propose to use a two-phase clustering algorithm consisting of an initial
      clustering phase and a second re-clustering phase. The proposed algorithm has
      several desirable features: (i) it utilizes both local and global information by
      computing both a "local" pairwise distance between two gene expression profiles
      in Phase 1 and a "global" probabilistic measure of interestingness of cluster
      patterns in Phase 2, (ii) it distinguishes between relevant and irrelevant
      expression values when performing re-clustering, and (iii) it makes explicit the
      patterns discovered in each cluster for possible interpretations. Experimental
      results show that the proposed algorithm can be an effective algorithm for
      discovering clusters in the presence of very noisy data. The patterns that are
      discovered in each cluster are found to be meaningful and statistically
      significant, and cannot otherwise be easily discovered. Based on these discovered
      patterns, genes co-expressed under the same experimental conditions and range of
      expression levels have been identified and evaluated. When identifying regulatory
      patterns at the promoter regions of the co-expressed genes, we also discovered
      well-known transcription factor binding sites in them. These binding sites can
      provide explanations for the co-expressed patterns.

PMID- 15852507
TI  - Clustering gene expression data with kernel principal components.
AB  - Kernel principal component analysis (KPCA) has been applied to data clustering
      and graphic cut in the last couple of years. This paper discusses the application
      of KPCA to microarray data clustering. A new algorithm based on KPCA and fuzzy C
      means is proposed. Experiments with microarray data show that the proposed
      algorithms is in general superior to traditional algorithms.

PMID- 15852508
TI  - Approximate matching of structured motifs in DNA sequences.
AB  - Several methods have been developed for identifying more or less complex RNA
      structures in a genome. All these methods are based on the search for conserved
      primary and secondary sub-structures. In this paper, we present a simple formal
      representation of a helix, which is a combination of sequence and folding
      constraints, as a constrained regular expression. This representation allows us
      to develop a well-founded algorithm that searches for all approximate matches of
      a helix in a genome. The algorithm is based on an alignment graph constructed
      from several copies of a pushdown automaton, arranged one on top of another. This
      is a first attempt to take advantage of the possibilities of pushdown automata in
      the context of approximate matching. The worst time complexity is O(krpn), where
      k is the error threshold, n the size of the genome, p the size of the secondary
      expression, and r its number of union symbols. We then extend the algorithm to
      search for pseudo-knots and secondary structures containing an arbitrary number
      of helices.

PMID- 15852509
TI  - Support vector machines for prediction and analysis of beta and gamma-turns in
      proteins.
AB  - Tight turns have long been recognized as one of the three important features of
      proteins, together with alpha-helix and beta-sheet. Tight turns play an important
      role in globular proteins from both the structural and functional points of view.
      More than 90% tight turns are beta-turns and most of the rest are gamma-turns.
      Analysis and prediction of beta-turns and gamma-turns is very useful for design
      of new molecules such as drugs, pesticides, and antigens. In this paper we
      investigated two aspects of applying support vector machine (SVM), a promising
      machine learning method for bioinformatics, to prediction and analysis of beta
      turns and gamma-turns. First, we developed two SVM-based methods, called BTSVM
      and GTSVM, which predict beta-turns and gamma-turns in a protein from its
      sequence. When compared with other methods, BTSVM has a superior performance and
      GTSVM is competitive. Second, we used SVMs with a linear kernel to estimate the
      support of amino acids for the formation of beta-turns and gamma-turns depending
      on their position in a protein. Our analysis results are more comprehensive and
      easier to use than the previous results in designing turns in proteins.

PMID- 15852510
TI  - The incomplete perfect phylogeny haplotype problem.
AB  - The problem of resolving genotypes into haplotypes, under the perfect phylogeny
      model, has been under intensive study recently. All studies so far handled
      missing data entries in a heuristic manner. We prove that the perfect phylogeny
      haplotype problem is NP-complete when some of the data entries are missing, even
      when the phylogeny is rooted. We define a biologically motivated probabilistic
      model for genotype generation and for the way missing data occur. Under this
      model, we provide an algorithm, which takes an expected polynomial time. In tests
      on simulated data, our algorithm quickly resolves the genotypes under high rates
      of missing entries.

PMID- 15852511
TI  - Exploring protein's optimal HP configurations by self-organizing mapping.
AB  - Self-organizing map (SOM) has been used in protein folding prediction when the HP
      model is employed. The existing work uses a square-like shape lattice with l = m
      x n points to represent the optimal compact structure of a sequence of l amino
      acids. In this paper, a general l'-size sequence of amino acids is self-organized
      in a two dimensional lattice with l (> l') points. The obtained minimum
      configuration then has a flexible shape, in contrast to the compact structure
      limited in the lattice. To fulfil this extension, a new self-organizing map (SOM)
      technique is proposed to deal with the difficulty of the unsymmetric input and
      output spaces. New competition rules in the training phase are introduced and a
      local search method is applied to overcome the multi-mapping phenomena. Several
      HP benchmark examples with up to 36 amino acids are tested to verify the
      effectiveness of the proposed approach in this paper.

PMID- 15852512
TI  - Three-dimensional definition of leaf morphological traits of Arabidopsis in
      silico phenotypic analysis.
AB  - The detection of phenotypic alterations of mutants and variants is one of the
      bottlenecks that hinder systematic gene functional studies of the model plant
      Arabidopsis. In an earlier study, we have addressed this problem by proposing a
      novel methodology for phenome analysis based on in silico analysis of polygon
      models that are acquired by 3-dimensional (3D) measurement and which precisely
      reconstruct the actual plant shape. However, 3D quantitative descriptions of
      morphological traits are rare, whereas conventional 2D descriptions have already
      been studied but may lack the necessary precision. In this report, we focus on
      six major leaf morphological traits, which are commonly used in the current
      manual mutant screens, and propose new 3D quantitative definitions that describe
      these traits. In experiments to extract the traits, we found significant
      differences between two variants of Arabidopsis with respect to blade roundness
      and blade epinasty. Remarkably, the detected difference between variants in the
      blade roundness trait was undetectable when using conventional 2D descriptions.
      Thus, the result of the experiment indicates that the proposed definitions with
      3D description may lead to new discoveries of phenotypic alteration in gene
      functional studies that would not be possible using conventional 2D descriptions.

PMID- 15852513
TI  - Dizzy: stochastic simulation of large-scale genetic regulatory networks.
AB  - We describe Dizzy, a software tool for stochastically and deterministically
      modeling the spatially homogeneous kinetics of integrated large-scale genetic,
      metabolic, and signaling networks. Notable features include a modular simulation
      framework, reusable modeling elements, complex kinetic rate laws, multi-step
      reaction processes, steady-state noise estimation, and spatial
      compartmentalization.

PMID- 15852514
TI  - Dizzy: stochastic simulation of large-scale genetic regulatory networks
      (supplementary material).

PMID- 15852515
TI  - The probability distribution for a random match between an experimental
      theoretical spectral pair in tandem mass spectrometry.
AB  - Proteomic techniques are fast becoming the main method for qualitative and
      quantitative determination of the protein content in biological systems. Despite
      notable advances, efficient and accurate analysis of high throughput proteomic
      data generated by mass spectrometers remains one of the major stumbling blocks in
      the protein identification problem. We present a model for the number of random
      matches between an experimental MS-MS spectrum and a theoretical spectrum of a
      peptide. The shape of the probability distribution is a function of the
      experimental accuracy, the number of peaks in the experimental spectrum, the
      length of the interval over which the peaks are distributed, and the number of
      theoretical spectral peaks in this interval. Based on this probability
      distribution, a goodness-of-fit tool can be used to yield fast and accurate
      scoring schemes for peptide identification through database search. In this
      paper, we describe one possible implementation of such a method and compare the
      performance of the resulting scoring function with that of SEQUEST. In terms of
      speed, our algorithm is roughly two orders of magnitude faster than the SEQUEST
      program, and its accuracy of peptide identification compares favorably to that of
      SEQUEST. Moreover, our algorithm does not use information related to the
      intensities of the peaks.

PMID- 15852516
TI  - Theoretically modeling microarray with the chemical equilibrium and
      thermodynamics.
AB  - To date, the idea that microarray may shed the light on cellular processes by
      identifying groups of genes that appear to be co-expressed seems to remain a
      dream. This is partly because that there are some blank (meaning the knowledge is
      unavailable) or even erroneous areas in the fundamental theory in this field.
      This paper attempts to present the digest of microarray hybridization system with
      chemical thermodynamics, theoretically clarifying some misunderstandings and
      looking for answers to some critical questions around this technology, such as
      the mechanisms and conditions of quantitative measuring by hybridization
      reaction, the reasons of inconsistency of the data and the analysis results and
      the solutions, how to analyze the data, etc. A theoretical model for the next
      generation of microarray is proposed. We believe that this model is universal,
      laying the foundation for microarray technology from array design through the
      data analysis.

PMID- 15852517
TI  - Hidden Markov Models, grammars, and biology: a tutorial.
AB  - Biological sequences and structures have been modelled using various machine
      learning techniques and abstract mathematical concepts. This article surveys
      methods using Hidden Markov Model and functional grammars for this purpose. We
      provide a formal introduction to Hidden Markov Model and grammars, stressing on a
      comprehensive mathematical description of the methods and their natural
      continuity. The basic algorithms and their application to analyzing biological
      sequences and modelling structures of bio-molecules like proteins and nucleic
      acids are discussed. A comparison of the different approaches is discussed, and
      possible areas of work and problems are highlighted. Related databases and
      softwares, available on the internet, are also mentioned.

PMID- 15852518
TI  - A novel combination of methods to assess sarcopenia and muscle performance in
      mice.
AB  - A novel combination of assays was developed to assess sarcopenia and muscle
      performance. Three techniques were tested to assess muscle function both during
      and upon termination of treatments designed to induce sarcopenia. In unsuspended
      (US) and hindlimb suspended (HS) mice, a Hindlimb Exertion Force Test (HEFT),
      cage wheel running, and in vitro muscle electrophysiology were performed. Twelve
      week old, mature male C57BL/6J mice were HS (n = 24) for two weeks, or served as
      US controls (n = 26). Both groups were subjected to a HEFT on day 13; that is,
      the maximum force exerted against a beam force transducer (2 lb. linear range,
      Transducer Techniques, Temecula CA) following applied tail shock stimulus (0.15
      mA, 300 msec). This test primarily evaluated the hindlimb muscles used for an
      escape response (i.e., hamstrings, quadriceps and calf muscles). Mice (n = 10
      11/group) were given voluntary access to running wheels for 7 days post treatment
      to evaluate muscle endurance. On day 13, HS mice showed a mean 18.9% (p = 0.002)
      decrease in the maximum force exerted compared to US mice. After 7 days of wheel
      running, HS running distance tended to decrease (13.2%, p = 0.084). HS mice ran
      an average of 2.0 km/day less than US control mice, with similar running
      patterns: distance declined on day 2 following completion of HS but increased
      steadily thereafter. With in vitro testing, the maximum soleus tetanus response
      decreased by 31.8% (p = 0.01) with HS, in agreement with the changes observed by
      the other assays. These three assays, combined, appear to provide effective and
      complementary ways to measure muscle performance and functional differences.

PMID- 15852519
TI  - Clinical features, diagnostic and therapeutic approaches to haematogenous
      vertebral osteomyelitis.
AB  - This article review the clinical features and the diagnostic approach to
      haematogenous vertebral osteomyelitis in order to optimise treatment strategies
      and follow-up assessment. Haematogenous spread is considered to be the most
      important route: the lumbar spine is the most common site of involvement for
      pyogenic infection and the thoracic spine for tuberculosis infection. The risk
      factors for developing haematogenous vertebral osteomyelitis are different among
      old people, adults and children: the literature reports that the incidence seems
      to be increasing in older patients. The source of infection in the elderly has
      been related to the use of intravenous access devices and the asymptomatic
      urinary infections. In young patients the increase has been correlated with the
      growing number of intravenous drug abusers, with endocarditis and with immigrants
      from areas where tuberculosis is still endemic. The onset of symptoms is
      typically insidious with neck or back pain often underestimated by the patient.
      Fever is present in 10-45% of patients. Spinal infections may cause severe
      neurological compromise in few cases, but mild neurological deficit, limited to
      one or two nerve roots, was detected in 28-35% of patients. The diagnosis of
      haematogenous vertebral osteomyelitis may be very difficult, as the symptoms can
      be sometimes not specific, vague or almost absent. The usual delay in diagnosis
      has been reported to be two to four months, despite the use of imaging
      techniques: in the early diagnosis of vertebral ostemyelitis is important the
      role of bone scintigraphy. The general principles for the management of spine
      infections are non operative, consisting of external immobilization and
      intravenous antibiotics, followed by oral antibiotics. Indications for surgery
      should be given in case of absence of clinical improvement after 2-3 weeks of
      intravenous antibiotics, persistent back pain and systemic effects of chronic
      infection and with presence or progression of neurological deficit in elderly or
      in cervical infection. Chronic ostemyelitis may require surgery in case of a
      development of biomechanical instability and/or a vertebral collapse with
      progressive deformity.

PMID- 15852521
TI  - [The 106th annual meeting of the Japan Surgical Society. Nagoya, Japan. May 11
      13, 2005. Abstracts].

PMID- 15852520
TI  - Mucoepidermoid carcinoma of the bronchus: a rare entity in childhood.

PMID- 15852522
TI  - Asymptomatic intracranial sewing needle: an unsuccessful infanticide attempt?

PMID- 15852523
TI  - The United Nations and human cloning: a debate on hold.

PMID- 15852524
TI  - Billing practices.

PMID- 15852525
TI  - Salivary-type hyperamylasemia in theophylline poisoning.

PMID- 15852526
TI  - Benumbed.

PMID- 15852527
TI  - Hypokalemic paralysis and rhabdomyolysis in distal renal tubular acidosis.

PMID- 15852528
TI  - Cardiopulmonary bypass in a child with hereditary angioedema.

PMID- 15852529
TI  - Neoplasms in three patients following Kawasaki disease.

PMID- 15852530
TI  - KCNJ2 mutation in intractable ventricular arrhythmia with Andersen's syndrome.

PMID- 15852531
TI  - A case of 2-year-old boy with tuberous sclerosis complicated with descending
      aortic aneurysm.

PMID- 15852532
TI  - [Effects of high +Gx during simulated spaceship emergency return on learning and
      memory in rats].
AB  - OBJECTIVE: To observe the effects of high +Gx during simulated spaceship
      emergency return on learning and memory in rats. METHOD: Thirty two male SD rats
      were randomly divided into control group, 7 d simulated weightlessness group, +15
      Gx/180 s group and +15 Gx/180 s exposure after 7 d simulated weightlessness
      group, with 8 rats in each group. The changes of learning and memory in rats were
      measured after stresses by means of Y-maze test and step-through test. RESULT: In
      Y-maze test, as compared with control group, percentage of correct reactions
      decreased significantly (P<0.01) and reaction time increased significantly
      (P<0.01) in hypergravity after simulated weightlessness group at all time after
      stress; as compared with +15 Gx group or simulated weightlessness group,
      percentage of correct reactions decreased significantly (P< 0.05) and reaction
      time increased significantly (P< 0.05) immediately after stress. In step-through
      test, as compared with control group, total time increased significantly (P<0.01)
      in hypergravity after simulated weightlessness group at 1 d after stress; latent
      time decreased significantly (P<0.01) and number of errors increased
      significantly (P< 0.01) at all the time after stress. As compared with +15 Gx
      group, total time increased significantly (P<0.05) immediately, 1 d after stress.
      As compared with simulated weightlessness group, total time and number of errors
      increased significantly (P<0.05) immediately after stress. CONCLUSION: It is
      suggested that +15 Gx/180 s and simulated weightlessness may affect the ability
      of learning and memory of rats. Simulated weightlessness for 7 d can aggravate
      the effect of +Gx on learning and memory ability in rats.

PMID- 15852533
TI  - [Reactivity of pulmonary arteries and thoracic aortae in rats under tail
      suspension and the effects of NOS inhibitor].
AB  - OBJECTIVE: To further disclose mechanisms in adaptation of pulmonary and systemic
      arteries to simulated microgravity (SM), so as to elucidate the mechanisms
      accounting for orthostatic intolerance after SM, and to explore a new kind of
      countermeasure for orthostatic intolerance. METHOD: 300 tail suspended (TS) rats
      were used as the model to simulate the physiological effects of microgravity.
      Vasoreactivity changes of rings sectioned from pulmonary artery (PA) and thoracic
      aorta (TA) to 68 mmoles/L KCl, plus phenylephrine (PE) and acetylcholine (ACh)
      were observed after 7 d and 14 d tail-suspension. After preconditioning with 10(
      5) moles/L N-nitro-L-arginine methyl ester (L-NAME) for 20 min, vasoreactivity
      changes of PA and TA to PE and ACh were respectively repeated. RESULT: The
      contractile responsiveness of PA and TA to KCl and PE decreased significantly or
      very significantly after TS7 d and TSI4 d. The dilatory reactivity of PA and TA
      to ACh after TS7 d had a significant or very significant increase, but reactivity
      of PA showed no change and TA showed only a tendency to increase after TS14 d.
      After preconditioning with 10(-5) moles/L L-NAME, responsiveness of PA to PE
      after TS7 d and TS14 d had no difference among the three groups, but
      responsiveness of TA to PE after TS7 d and TS14 d had a significant decrease. The
      dilatory reactivity of PA after TS7 d decreased significantly or very
      significantly, and the remains showed no significant change. CONCLUSION: The
      decrease of contractile responsiveness of PA and TA might be due to the increased
      dilatory function of the endothelial cells. The fact that 10(-5) moles/L L-NAME
      reversed the decrease of contractile responsiveness of PA and partly of TA after
      tail suspension implicates that there might be an inhibitory action on the
      dilatory function of the endothelial cells. The NOS inhibitors may be helpful in
      preventing orthostatic intolerance.

PMID- 15852534
TI  - [Daily 4-h standing can prevent soleus atrophy induced by 4 weeks tail suspension
      in rats].
AB  - OBJECTIVE: To observe the effects of intermittent standing in counteracting the
      soleus atrophy induced by simulated microgravity. METHOD: Eighteen male Sprague
      Dawley rats were randomly assigned to 3 groups: control (CON), four-week tail
      suspension (TS), and TS plus daily 4 h standing (TS + STD4). After 4 weeks,
      bilateral adrenal glands and soleus muscle were dissected and weighed. The left
      soleus was sectioned with cryostat and stained with ATPase staining. The cross
      sectional area (CSA) of type I and II fibers and the relative proportion of type
      I fibers were measured using Leica image analysis system. The right soleus was
      homogenized and stained with Coomassie Brilliant Blue following electrophoresis
      on 8% SDS-PAGE under 70 V and < 4 degrees C for 28 h. The Scion image software
      was used to evaluate the result of the densitometry of different types of MHC.
      RESULT: In TS, wet weights of the soleus, CSA of type I and II fibers, and
      proportion of type I fibers decreased obviously, as compared with those rats in
      CON (P<0.01 or P<0.05). The SDS-PAGE showed similar results as by ATPase staining
      in the proportion of MHC I. Whereas in TS + STD4, there were no significant
      differences of those parameters compared with those rats in CON. CONCLUSION:
      Daily 4-h standing fully prevented the soleus atrophy induced by simulated
      microgravity for 4 wk in rats.

PMID- 15852535
TI  - [Effects of three Chinese traditional drugs on afferent discharge from single
      muscle spindle in toads].
AB  - OBJECTIVE: To shed some light on treatment of muscle atrophy through testing the
      effects of several Chinese traditional drugs that can invigorate blood
      circulation on the afferent discharge of muscle spindle. METHOD: Single muscle
      spindle was isolated from sartorius muscle of toad. Afferent discharge from the
      muscle spindle was recorded using air-gap technique and effects of three Chinese
      traditional drugs on afferent activity of the muscle spindle were observed.
      RESULT: Ligustrazine could markedly tingle the spontaneous electrical activity of
      the muscle spindle, and it also showed a good dose-response relationship, while
      Salvia Miltiorrhiza and Safflower had no such excitative effect. CONCLUSION: It
      is known that ligustrazine can expand blood vessels and agitate microcirculation,
      and this effect on the muscle spindle makes it helpful for persons with muscle
      atrophy.

PMID- 15852536
TI  - [A study on etiology and pathogenic mechanism of decompression sickness].
AB  - OBJECTIVE: To explain the etiology of decompression sickness (DCS) and to
      elucidate its pathogenic mechanism. METHOD: Tunica conjunctiva was examined by
      microscopy and blood pressure was measured at the exposed femoral arteries in
      inadequately decompressed animals after hyperbaric exposure. Then pathological
      examinations were done. RESULT: Animals with vascular spasm and dysfunction after
      decompression showed DCS symptoms. Severe DCS was found in the period of
      increasing of blood pressure swelling. Appeared in endothelial cells, fracted,
      hemorrhages were also formed in the body of DCS animals. CONCLUSION: DCS is a
      disease with vascular spasm and dysfunction caused by decompression. It's
      resulted from anoxia or pathological change caused by vascular spasm, dysfunction
      or even failure of blood vessels due to the gas tension (etiology) provoked by
      supersaturated gas in the blood during descending of ambient pressure. Vascular
      spasm and dysfunction impede the elimination of gas from the blood, and once the
      gas amount is sufficient to cause severe ischemia of the circulation system, the
      state of disease would be severe.

PMID- 15852537
TI  - [Effects of acute hypoxia on expression of heat shock protein 70 in cochlea of
      guinea pigs].
AB  - OBJECTIVE: To investigate the changes of the expression of heat shock protein 70
      (HSP70) in the cochlea of guinea pigs under acute hypoxia. METHOD: Different
      degrees of acute hypoxia were imposed on guinea pigs and slices of the cochlea
      were examined by immunohistochemistry to detect HSP70. RESULT: In normal
      situation, HSP70 is expressed in guinea pig's cochlea, especially in spiral
      ganglion and Corti's organ, under acute hypoxia, this expression was
      strengthened, and the degree of this strengthening showed no correlation with
      degree of hypoxia. CONCLUSION: These results suggest that acute hypoxia can
      strengthen the expression of HSP70 in guinea pig's cochlea, and the degree of
      hypoxia has no effects on the degree of this strengthening. The expression of
      HSP70 in the cochlea may be a kind of protection to the structure and the
      function of the inner ear.

PMID- 15852538
TI  - The carbon or silicon colonization of the universe?
AB  - At the time of the Apollo Programme, a first human mission to Mars was proposed
      as early as 1984 with the argument that the higher costs of human exploration
      would be more than justified by the increased effectiveness of human explorers.
      This was based on the Apollo experience, where "ground truth" measurements and
      sampling provided the basis for subsequent unmanned exploration of the Solar
      System. A human Mars mission is now not seen until 2030, at the end of a series
      of increasingly sophisticated unmanned probes. Each robot mission not only
      teaches us something about Mars, but also through experience increases our
      capabilities for the unmanned exploration of that planet. As a consequence, what
      a human mission would have to do becomes progressively more demanding. Any
      extended plan for the human exploration of Space will tend to be overtaken by
      advances in technology, and if this is not factored into the scenario the
      proposals will become progressively unrealistic.

PMID- 15852539
TI  - Physiological and biomechanical considerations for a human Mars mission.
AB  - Evolving on Earth has made humans perfectly adapted, both physiologically and
      biomechanically, to its gravity and atmospheric conditions. Leaving the Earth and
      its protective environment, therefore, results in the degradation of a number of
      human systems. Long-duration stays on the International Space Station (ISS) are
      accompanied by significant effects on crew's cardiovascular, vestibular and
      musculoskeletal systems. Bone loss and muscle atrophy are experienced at a rate
      of 1-3% and 5% per month respectively, while VO2 (oxygen consumption)
      measurements are reduced by approximately 25% after a few weeks in space. If
      these figures are simply extrapolated, a future human mission to Mars will be
      seriously jeopardised and crews may find they cross the threshold of bone and
      muscle loss and aerobic fitness--ultimately with them being unable to return to
      Earth. When arriving on Mars, considerable biomechanical alterations will also
      occur. Optimum walking speeds will be approximately 30% lower and transitioning
      from a walk to a run will occur at a speed 25% slower. Peak vertical forces will
      be reduced by as much as 50%, while stride length, stride time and airborne time
      will all increase. On Mars, half as much energy will be required to travel the
      equivalent distance on Earth and it will be 65% more economical to run rather
      than to walk.

PMID- 15852540
TI  - [Pregnancy and tobacco].

PMID- 15852541
TI  - W.W.W. MOON? The why, what and when of a permanent manned lunar colony.
AB  - Several reasons for going back to the Moon are listed: scientific study of our
      natural satellite, Earth and in general the Solar System; exploitation of the
      resources of Outer Space; geopolitical considerations that made Apollo possible
      and are still valid in the long term; advancement of manned spaceflight, as robot
      based exploration is time-wise inefficient and politically negligible.
      Technological, organisational and legal challenges are then outlined. After a
      discussion of human physiology, building materials and transportation of people
      and goods, an underground polar location is proposed as settlement site, either
      within kilometre-size lava tubes or man-made caves. An analysis of spaceflight
      history is conducted to determine a target date for returning to the Moon to
      stay. In the absence of political or commercial competition, experience indicates
      the last decades of the XXI century. To shorten this timescale, it is recommended
      to focus on accomplishing the task of establishing a reliable lunar travel and
      settlement system, rather than developing new technologies: simplifying the goals
      of each single step forward (as was the case of the Clementine mission) and
      concentrating on production-ready (or almost-ready) equipment (compare the ill
      fated X-33 to the dependable Soyuz capsules).

PMID- 15852542
TI  - A human galaxy: a prehistory of the future.
AB  - In the very long term, how could humans colonise the Galaxy? Colonisation cannot
      be centrally controlled; deeper drives must be tapped. It may take centuries to
      colonise the nearest stars: it may be a 'programme' like the Industrial
      Revolution, fuelled by entrepreneurship. To build a respectable interstellar
      empire may take millennia. Religions are similar multigenerational projects.
      Perhaps colonists will be motivated by appropriate creeds. To win the Galaxy,
      starship technology must persist for tens or hundreds of millennia. Homo erectus
      made the same hand-axe for a million years. The driver was biological, not
      conscious. Perhaps to our descendants starships will be like peacock tails.

PMID- 15852543
TI  - Importance of X-ray in chronic stridor.

PMID- 15852544
TI  - Perceptual analysis of speech and the activity in the lateral pharyngeal walls
      before and after velopharyngeal flap surgery.
AB  - The purpose of this study was to investigate the effects of velopharyngeal flap
      surgery on speech and its relation with the activity in the lateral pharyngeal
      walls. Videofluoroscopic recordings made before and after operation were used in
      this retrospective study, which comprised 28 patients who had pharyngeal flap
      surgery between 5:5 and 14:3 (mean 8:6) years:months of age at the Sahlgrenska
      University Hospital, Goteborg, Sweden. Twenty-four patients had different types
      of clefts and four had velopharyngeal impairment (VPI) without a cleft palate.
      Eleven had additional malformations. Speech and activity in the lateral
      pharyngeal walls were perceptually preoperatively and postoperatively. The study
      confirmed that patients with VPI can be helped by a velopharyngeal flap
      operation. There seemed to be a relation with the activity in the lateral
      pharyngeal wall and speech. The later the postoperative assessment, the better
      the speech, but the age at operation did not affect the result. The impact of
      additional anomalies and syndromes should be investigated further.

PMID- 15852545
TI  - Commentary on "Noninvasive detection of multidrug resistance in patients with
      hematological malignancies: are we there yet?".

PMID- 15852546
TI  - [Relationship between respiration exchange ratio and muscle oxygen content
      measured by near-infrared spectroscopy].
AB  - OBJECTIVE: To study the relationship between respiration exchange ratio (RER) and
      tissue oxygen content in human skeletal muscle. METHOD: Using a portable tissue
      oximeter based on near-infrared spectroscopy (NIRS), the relative changes of
      skeletal muscle oxygen content were measured non-invasively and in vivo when
      healthy volunteers were performing an incremental intensity running protocol. The
      results were compared with heart rate (HR), VO2, VCO2, and RER. RESULT: In the
      experiment, the change in skeletal muscle oxygenation content of the volunteers
      was regular and has a significant close relationship to HR, VO2 and RER (P=0.01).
      CONCLUSION: It shows that NIRS is a new photonic technology which provides a
      measurable biomedical parameter for the evaluation of athlete's physique and
      training effect. It offers reference for monitoring and assessing training effect
      in vivo, real-time and non-invasively.

PMID- 15852547
TI  - [Protective effect of Danzhi-xiaoyao San on rat brain energy or material
      metabolism (correction of matebolism) dealt with D-galactose].
AB  - OBJECTIVE: To research the mechanism of Danzhi-xiaoyao San (DZXYS) for treating
      Alzheimer's disease model of rats dealt with D-galactose. METHOD: An Alzheimer's
      disease-like model of rats has been set up with sc. D-galactose 150.0 mg kg-1 D-1
      x 49 d. Comparing with Acricept in 0.54 mg kg-1 D-1 dosage as a positive control
      drug, DZXYS in 12.636 g kg-1 D-1 x 49 d dosage has orally been administrated
      orally to treat the injury in the Alzheimer's disease-like model of rats. The
      energy charge in the cerebral tissues had been detested with waters liquid
      chromatography; the protein content and DNA content in the cerebral tissues had
      been detested with ultraviolet assay, the relative content of aldose reductase
      mRNA is detested with RT-PCR. The difference was analyzed between the control
      rats without D-galactose, the model rats dealt with D-galactose, the model rats
      treated with Aricept and the model rats treated with DZXYS, it is significant as
      P<0.05. RESULT: 1) DZXYS can not affect the energy charge in their cerebral
      tissues. 2) DZXYS can increase the protein content from 0.3139 +/- 0.019468 to
      0.3213 +/- 0.015528 (ni=10, P>0.05) in their cerebral tissues. 3) DZXYS can
      increase the total DNA content from 1.093 +/- 0.267 to 1.488 +/- 0.341 (ni=10,
      P<0.01) in their cerebral tissues. 4) DZXYS can increase the content of AR-mRNA
      in their cerebral tissue from 0.732 +/- 0.159 to 1.418 +/- 0.277 (ni=5, P<0.01).
      CONCLUSION: It suggests that DZXYS could be effective in human Alzheimer's
      disease for its stabling gene expression, maintaining protein characteristics,
      recovering signal transduction in the Alzheimer's disease-like model rats dealt
      with D-galactose.

PMID- 15852548
TI  - [Development of a prototype of space vegetable-cultivating facility for ground
      based experiments].
AB  - OBJECTIVE: To develop a ground-based experimental prototype of space vegetable
      cultivating facility (GEPSVF), so as to solve the main key techniques related to
      higher plant cultivation in space environmental conditions, and to further lay a
      foundation for future development and application of the prototype of space
      vegetable-growing facility. METHOD: Based on detailed demonstration and design of
      technique plan, the blueprint design and machining of components, whole facility
      installment, debugging, trial operations and verification experiments were done.
      RESULT: The parameters in the growing chamber such as temperature, relative
      humidity, wind velocity, total pressure, O2 partial pressure, CO2 partial
      pressure and water content of the growing media were totally and effectively
      controlled; the light source was electronic fluorescent lamp; the average
      vegetable-producing output reached 60 g (fresh weight) d-1. CONCLUSION: The
      prototype could operate stably; its actual performance indexes achieved the
      expected ones basically; some of its operating principles can adapt to space
      microgravity condition. Therefore, the prototype is a good beginning for future
      development of space vegetable-producing facilities.

PMID- 15852549
TI  - [Development of a special controlled-releasing long effect fertilizer used in
      controlled ecological life support system].
AB  - OBJECTIVE: To develop a special controlled-releasing long effect fertilizer
      (SCRLEF) for growing higher plant in controlled ecological life support system
      (CELSS). METHOD: First, a plan was designed. According to requirements, some
      original fertilizers were chosen and compounded in proper proportions, and a
      granule product was obtained and encapsulated in certain materials to form
      SCRLEF. Then, experiments were done by measuring the content and releasing-rate
      of the fertilizer, and cultivating plants with the fertilizer. RESULT: The
      fertilizer contains nutrients for plant growing, such as: N 18.0%, P2O5 14.3%,
      K2O 12.6%, Ca 2.6%, S 3.5%, Mg 0.12%, and other micro-nutrients. The granules of
      the SCRLEF are uniform in size with diameters form 2.5 mm to 4.0 mm. Under 20-25
      degrees C, the cumulative amounts of released nutrients from the fertilizer in 10
      d, 20 d, 30 d, 40 d, and 50 d, are 7.9%, 21.6%, 40.5%, 50.2%, 60.9% respectively,
      within 10 d, 20 d, 30 d, 40 d, 50 d. By cultivating lettuce with the fertilizer,
      we found that the vegetable could grow normally, and there wasn't any deficiency
      symptom in the plants within 45 d. CONCLUSION: The design consideration of the
      SCRLEF is reasonable. The fertilizer provides total nutrients for plant growing,
      and can be used to supply the required nutrients for the plants grown in the
      CELSS.

PMID- 15852551
TI  - [An experimental study of the effect of structure sealing of infrared CO2 sensor
      on its accuracy].
AB  - OBJECTIVE: To study the effect of structure sealing of infrared CO2 sensor on its
      accuracy. METHOD: Two experiments were designed. The IR CO2 sensor based on
      infrared principle and no comparing lighting path with only one beam of light
      were calibrated in one experiment, and in the other experiment the sensors were
      placed in an environment simulating the practical condition. The temperature,
      pressure and standard gas were kept same in the two experiments while CO2
      concentrations in the dead volume were varied. RESULT: Readings from the sensors
      varied with the variation of the CO2 concentration in the dead volume of the
      sensors. CONCLUSION: The structure sealing of the IR CO2 sensor has great
      influence on its accuracy. A sealed dead volume in the IR CO2 sensor can decrease
      or eliminate the effect.

PMID- 15852550
TI  - [An experimental study of effects of active-heating-system for extravehicular
      spacesuit gloves on working performance].
AB  - OBJECTIVE: To observe the effects of active heating system for spacesuit gloves
      on extravehicular working performance. METHOD: After analyzing the factors with
      gloves influence on the working performance, the effects of active heating system
      for gloves were studied experimentally with aspects to fatigue, hand strength,
      dexterity and tactile sensing. RESULT: 1) Heating-system had not influence to
      grip; 2) Heating-system had 17% influence to fatigue except specific person; 3)
      Nut assembly and nipping pin showed that heating-system had little influence to
      dexterity; 4) Apperceiving shape of object and two-point distance showed heating
      system had little influence to tactility. CONCLUSION: The active heating method
      is rational and has little influence on working performance.

PMID- 15852552
TI  - [Simulation of the rat tibial bone density changes with the finite element
      method].
AB  - OBJECTIVE: To calculate changes of rat tibial density induced by mechanical load
      with the finite element method. METHOD: A three-dimensional computer model was
      formed by processing the industrial CT image of rat tibia; bone remodeling
      results were predicted by using the internal bone remodeling theory presented by
      Beaupre in conjunction with the finite element method. RESULT: The increments of
      the elements density and its distribution plot were obtained. CONCLUSION: The
      simulation results agree well with the results of the biological experiment, so
      the simulation results were proved to be accurate.

PMID- 15852553
TI  - [Application of fractal dimension in heart rate variability analysis during head
      down tilt].
AB  - OBJECTIVE: The paper applies the fractal dimension to heart rate variability
      (HRV), and discusses the changes of the fractal dimension of cardiovascular
      system during head down tilt (HDT). METHOD: ECG of 10 subjects were recorded
      during HDT, the experiment was repeated in each subject. Fractal dimension was
      used to analyze the HRV. RESULT: Compared to supine before HDT, the standard
      deviation of all normal to normal RR intervals (SDNN) at 15-20 min, 20-25 min, 25
      30 min and restoration increased significantly; the root mean square of
      successive differences between adjacent normal cycles (rMSSD) at 20-25 min
      increased significantly; the fractal dimension at 0-5 min, 5-10 min, 10-15 min,
      20-25 min, 25-30 min and restoration increased significantly. CONCLUSION: The
      result shows that HRV and the nonlinearity of cardiovascular system increase
      during HDT. It is feasible that the fractal dimension can be used for analyzing
      HRV.

PMID- 15852554
TI  - [Method for segmenting medical image based on anatomical model].
AB  - OBJECTIVE: To improve the automatization and reliability of medical image
      segmentation. METHOD: An anatomical model was built and used to guide the low
      level segmentation process. The system architecture was made up of an anatomical
      model, image processing routines and an inference engine, the interaction of
      which are governed by a blackboard. RESULT: The result of application of the
      segmentation for chest CT image was satisfactory and needs less operator
      intensive. CONCLUSION: This method improves automatization and reliability of the
      medical image segmentation. Because of the good expansibility, it may serve as a
      template for knowledge-based processing of medical image.

PMID- 15852555
TI  - [Development of a portable ECG and blood pressure monitor based on personal
      digital assistant (PDA)].
AB  - OBJECTIVE: To develop a portable multifunctional electrocardiograph (ECG) and
      blood pressure monitor with its convenience to use. METHOD: It consisted of the
      electrocardiograph and blood pressure monitor module, microprocessor module and a
      personal digital assistant (PDA), to implement the functions of ECG/blood
      pressure signal automatic monitoring and remote data transferring to the
      hospital. RESULT: Under the control of the microprocessor, the monitor module can
      achieve the ECG signal, the blood pressure signal and transmit the data to the
      PDA. The program runs in PDA, integrating the capabilities of data waveform
      browsing and remote data transfering. CONCLUSION: The monitor meets the design
      requirements and has a good future for application.

PMID- 15852556
TI  - [Random amplified polymorphic DNA analysis of tomato from seeds carried in
      Russian Mir space station].
AB  - OBJECTIVE: To identify the variation of hereditary substance of tomato offspring
      from seeds under long-duration spaceflight condition. METHOD: The tomato seeds
      carried in Russian MIR space station for six years, and the ground-based control
      were planted on the ground. The leaves of plants were used to do random amplified
      polymorphic DNA (RAPD) analysis. RESULT: Forty random primers were used in this
      study, among which 31 primers generated the same DNA band type, and 9 primers
      generated different DNA band types. Forty primers amplified 269 DNA bands, among
      which 29 DNA bands were polymorphic ones with a percentage of polymorphism of
      10.8%. Compared with the control, plants from seeds carried in space station
      generated different band types. Band types were different among five plants from
      seeds carried in space station. The number of polymorphic bands generated by
      plant No. 5 compared with the control was the most, and that by plant No. 2 was
      the least. CONCLUSION: Long-duration spaceflight can cause variation of
      hereditary substance DNA of tomato.

PMID- 15852557
TI  - [Research progresses on deformable model in medical image processing].
AB  - In recent years, image processing technique based on deformable models has been
      widely used in the field of medical image processing and analysis. This survey
      demonstrates the principle of two kinds of basic deformable models, i.e.
      parametric deformable model and geometric deformable model. The design of model
      in application is also discussed. By incorporating prior knowledge and modeling
      global properties, several new extensions of basic deformable model are then
      reviewed. At last, some prospects of possible research are given.

PMID- 15852558
TI  - What's new in Nicotine and Tobacco Research?

PMID- 15852559
TI  - Artificial gravity.

PMID- 15852560
TI  - In memoriam George L. Wied, M.D., D.Sc. (hon), F.I.A.C. February 7, 1921-July 25,
      2004.

PMID- 15852561
TI  - Report of the Inner City Task Force of the Royal College of General
      Practitioners.

PMID- 15852562
TI  - General practice and clinical pharmacology--bridging the gap.

PMID- 15852563
TI  - Education and general practice: the future.

PMID- 15852564
TI  - Evaluation of drug education--another suitable case for treatment?
AB  - Drug Education may be evaluated in two ways: by examination of what a doctor
      knows, or by audit of what a doctor does. Since knowledge does not necessarily
      determine performance, the audit approach is more appropriate. It has three
      requirements: --detailed prescribing data must be available for the purpose of
      comparison; --drug volumes must be measured accurately, and prescribing rates be
      standardized for the age-sex structure and morbidity of the practice population; 
      -valid standards must be established. In the United Kingdom detailed prescribing
      data are available. However, methods of measurements are unsatisfactory and
      standards are based either on local averages of dubious worth, or on an approach
      that is negative and often arbitrary. The work of the Prescribing Research Unit
      at Leeds in addressing these problems is described.

PMID- 15852565
TI  - Prescribing decisions in general practice--learning and changing.
AB  - The key to changing the prescribing behaviour of doctors is to understand the
      decision-making processes underlying their prescribing. Prescribing decisions
      have been described as a two-stage process. The first stage is to consider a
      range of possible treatment options and the second stage is to make a selection
      from among these. A large number of non-pharmacological influences have been
      identified as operating between the first and second stage. These emanate chiefly
      from influences being brought to bear on the process by patients, doctors other
      than the prescriber, the pharmaceutical industry and from the funders of health
      care. Doctors need to acquire a range of new knowledge and skills to deal with
      these pressures to prescribe. Among these are skills in negotiating with
      patients; an appreciation of the realities of decision making in primary (as
      opposed to secondary) care; skills in the critical appraisal of drug company
      claims and dealing with the marketing skills of pharmaceutical company sales
      representatives; and knowledge of and skills in health economics to deal with the
      concerns of health care funders. In addition, new ways of working with these and
      other interested parties need to be evolved and certain decisions may be more
      appropriately considered and taken in situations other than face to face with
      patients.

PMID- 15852566
TI  - Impact of feedback and peer review on prescribing.

PMID- 15852567
TI  - Can feedback on prescribing be integrated into continuing medical education?

PMID- 15852568
TI  - Can rational prescribing be summatively assessed?

PMID- 15852569
TI  - The prescribing jigsaw: getting prescribing costs into perspective.

PMID- 15852570
TI  - Drug formularies--helpful tools for drug education?

PMID- 15852571
TI  - Professionalism in central service.

PMID- 15852572
TI  - Ophthalmologists cleared in two cases,.

PMID- 15852574
TI  - Mutual expectations of laymen and religious.

PMID- 15852573
TI  - Improvement and control of performance in the laboratory.

PMID- 15852575
TI  - Sisters share with retarded men.

PMID- 15852576
TI  - Educational preparation for hospital religious.

PMID- 15852577
TI  - The religious congregation and the hospital.

PMID- 15852578
TI  - Responsibilities of trustees.

PMID- 15852579
TI  - Relieving the nursing shortage...what administration can do.

PMID- 15852580
TI  - Sound receiving procedures--a must for purchasing.

PMID- 15852581
TI  - Professional pill pusher.

PMID- 15852582
TI  - Small-town pharmacists wanted.

PMID- 15852584
TI  - Winning team.

PMID- 15852583
TI  - Adoption agent.

PMID- 15852585
TI  - Race and a heart drug.

PMID- 15852586
TI  - Take my advice.

PMID- 15852587
TI  - Physicians' plan for a healthy Minnesota.

PMID- 15852588
TI  - Lawmakers hear from physicians during Day at the Capital.

PMID- 15852589
TI  - Safe sedation.

PMID- 15852590
TI  - When short is not sweet.

PMID- 15852591
TI  - When genes and drugs collide.

PMID- 15852592
TI  - The Vioxx fallout.

PMID- 15852593
TI  - Direct-to-Consumer advertising for prescription drugs.

PMID- 15852594
TI  - Secrecy in medical journals.

PMID- 15852595
TI  - Beyond the sales pitch and samples.

PMID- 15852596
TI  - What will the new medicare drug benefit mean for Minnesota physicians?
AB  - The Medicare Modernization Act passed by Congress in 2003 included a prescription
      drug benefit that will go into effect in January 2006. In addition to providing
      prescription drug coverage, the new benefit presents physicians and their
      patients with a complex set of procedures and regulations. This article explores
      the historical context for the law, the effects of the interim benefit for 2004
      and 2005, the provisions of the benefit, and the implications for Minnesota
      seniors and their physicians.

PMID- 15852597
TI  - Influenza 2004--2005: the best of times, the worst of times.
AB  - Last year's flu vaccine shortage caught public health officials around the
      country off guard. Minnesota's efforts to locate vaccine within the state and
      distribute extra doses to areas with the greatest need paid off, as the state was
      able to make vaccinations available to people who were at greatest risk--and
      eventually to everyone else--long before the rest of the country. This article
      looks at how officials in Minnesota handled the situation and how better
      communication and development of a Web-based data collection tool to assess and
      project the supply of vaccine could better prepare the state for another
      shortage.

PMID- 15852598
TI  - A perspective on U.S. drug reimportation.

PMID- 15852600
TI  - [To serve life--to love people].

PMID- 15852601
TI  - [Attitudes in nursing--2d part].

PMID- 15852602
TI  - [Nursing care of patients with thoracic drainage after cardiothoracic surgery].

PMID- 15852603
TI  - [Sadya--a life story].

PMID- 15852604
TI  - [Sex behavior of adolescents].

PMID- 15852606
TI  - [National health plan--perspective of the Church--intervention of the health
      pastoral. Conclusions].

PMID- 15852605
TI  - [Nursing education: what are the challenges?].

PMID- 15852607
TI  - The CSI effect.

PMID- 15852608
TI  - Germs on the loose: a deadly flu virus somehow got mailed to laboratories around
      the world.

PMID- 15852609
TI  - No scientific consensus on silicone breast implants Health risk or a woman's
      choice?

PMID- 15852610
TI  - Auditors sound alarm bells in Surrey and Sussex cash crisis.

PMID- 15852611
TI  - 'Entertainment advisors' under attack.

PMID- 15852612
TI  - Hutton leaves options open over SHA future.

PMID- 15852613
TI  - Sexual health. Why PCTs are reluctant to rise to the challenge.

PMID- 15852614
TI  - On the dangers of pessimism.

PMID- 15852615
TI  - A matter of life and death. Interview by Nick Edwards.

PMID- 15852616
TI  - Data briefing. Waiting times. Cancer treatment variations persist.

PMID- 15852617
TI  - NHS activists. Health's angels.

PMID- 15852618
TI  - On clinical management. How can we make space for a sane and well-balanced life?

PMID- 15852619
TI  - Finance: the English job. Interview by Lynne Greenwood.

PMID- 15852620
TI  - Staff survey. Listen very carefully.

PMID- 15852621
TI  - [Effects of propofol and thiamylal on nicorandil induced ATP-sensitive potassium
      channel activities in cultured rat aortic smooth muscle cells].
AB  - BACKGROUND: Nicorandil, a hybrid ATP-sensitive potassium (K(ATP)) channel opener
      and nitrate compound, is used clinically for the treatment of angina pectoris. In
      the present study, we investigated the effects of propofol and thiamylal on
      sarcolemmal K(ATP) channels activities induced by nicorandil in cultured rat
      aortic smooth muscle cells. METHODS: We used inside-out patch clamp
      configurations to investigate the effects of propofol and thiamylal on nicorandil
      induced K(ATP) channel activities. RESULTS: K(ATP) channel was not spontaneously
      activated by patch excision in the absence of intracellular ATP. Application of
      nicorandil (100 microM) induced a marked activation of KATP channel currents,
      which was completely blocked by 3 microM glibenclamide, the sulfonylurea that
      blocks K(ATP) channels. Nicorandil induced KATP channel currents were not
      significantly inhibited by application of 10 and 100 microM propofol to
      intracellular surface. However, application of 100 and 300 microM thiamylal to
      intracellular surface significantly inhibited the nicorandil induced K(ATP)
      channel currents, with relative channel activities decreasing to 0.65 +/- 0.08
      and 0.46 +/- 0.10 of control, respectively. CONCLUSIONS: Propofol had no effect
      on nicorandil induced sarcolemmal KATP channel activities in rat aortic smooth
      muscle cells, whereas thiamylal significantly inhibited these channel activities
      at clinically relevant concentrations.

PMID- 15852622
TI  - [Mouth opening in relation to the craniocervical position during induction of
      general anesthesia].
AB  - BACKGROUND: Decreased mouth opening and limited neck mobility sometimes make
      direct laryngoscopy or tracheal intubation difficult and compromise the safety in
      establishing the airway during induction of general anesthesia. Recent report
      indicated that mouth opening was related to the craniocervical position in awake
      subjects. The query about whether the neck position modulate the mouth opening
      during anesthetic induction under paralyzed condition is not clarified. We
      hypothesized that the neck extension and the flexion induce changes in inter
      incisor distance (IID) during anesthetic induction. METHODS: Thirty relatively
      young patients for general anesthesia were (male; 20, female; 10) subjected. IID
      was measured with his/her neck positioned flexed, neutral and extended in the
      sagittal plane, each at preanesthetic awake period, and during anesthetic
      induction period. The effect of sniffing position on the mouth opening was also
      studied. RESULTS: At preanesthetic period, IID (mean +/- SD in mm) at neck
      flexion (37.4 +/- 7.8) was significantly shorter than both at neutral (44.1 +/-
      7.5) and at extension (47.4 +/- 7.0). During induction, significant increase in
      IID was observed as patients' neck position changed from flexed (31.8 +/- 5.4) to
      neutral (36.6 +/- 5.4), and extended, (41.7 +/- 8.3). Sniffing position did not
      affect the mouth opening both at preanesthetic and during anesthetic induction
      period. CONCLUSIONS: Craniocervical extension may play a desirable role in the
      airway management with mouth opening widely during anesthetic induction under
      neuromuscular blockade.

PMID- 15852623
TI  - [Clinical study of vecuronium maintenance speed in trigeminal microvascular
      decompression surgery].
AB  - BACKGROUND: Patients receiving chronic carbamazepine therapy may be resistant to
      vecuronium. The purpose of this study was to determine maintenance speed of
      vecuronium in trigeminal microvascular decompression surgery. METHODS: The
      vecuronium maintenance speed of the patient for microvascular decompression
      diagnosed as trigeminal neuralgia (group T: n=18) or hemi-facial spasm (group C:
      n=18) was examined retrospectively. Anesthesia was induced with propofol,
      ketamine, midazolam and buprenorphine. Vecuronium was given to facilitate
      tracheal intubation. The patients received balanced anesthesia with infusion of
      propofol, ketamine, buprenorphine and vecuronium (60-80 microg x kg(-1) x h(-1)),
      with nitrous oxide. In both groups the scheduled vecuronium maintenance speed was
      increased if needed, using the TOF-Watch, at the time of body movement or with
      more than four TOF count. RESULTS: All patients of group T were medicated with
      carbamazepine before operation. None of C received carbamazepine. With C,
      vecuronium maintenance speed was as scheduled. With T, however, scheduled
      vecuronium speed increased in most of the cases. Actual vecuronium speed was
      significantly faster with T, compared with C. Although actual speed divided by
      scheduled speed was 1 in group C, it was 1.4 in T. CONCLUSIONS: Vecuronium
      maintenance speed is 1.4 times of scheduled speed in patients medicated with
      carbamazepine.

PMID- 15852624
TI  - [The antiemetic effect of dexamethasone during continuous subcutaneous infusion
      of morphine for postoperative pain relief].
AB  - BACKGROUND: Dexamethasone is known to reduce the incidence of postoperative
      nausea and vomiting, associated with perioperative intrathecal, epidural, or
      intravenous morphine. However, the effect of dexamethasone on subcutaneous
      morphine is unclear. Therefore, we evaluated the antiemetic effect of intravenous
      dexamethasone during continuous subcutaneous infusion of morphine for
      postoperative pain relief. METHODS: Twenty patients scheduled for spinal surgery
      under general anesthesia were enrolled in this randomized, double-blind, and
      placebo-controlled study. The dexamethasone group (n=10) received dexamethasone 8
      mg and the saline group (n=10) received the same amount of saline before the
      induction of anesthesia. Anesthesia was maintained with propofol and fentanyl.
      Postoperative pain was treated with continuous subcutaneous morphine via a
      patient-controlled analgesia device. Postoperatively patients were assessed
      during 48 hours for nausea and vomiting. RESULTS: Nausea or vomiting ascribable
      to the subcutaneous morphine developed in 40% of the patients in each group
      (P:NS). CONCLUSIONS: Our results suggest that the single dose of dexamethasone (8
      mg) does not reduce postoperative nausea and vomiting associated with continuous
      subcutaneous infusion of morphine after spinal surgery.

PMID- 15852625
TI  - [A retrospective study on awareness in 1922 cases during induction of general
      anesthesia].
AB  - BACKGROUND: There are some reports on the incidence of awareness during general
      anesthesia that is usually stable at the maintenance period. The aim of this
      study is to evaluate the incidence of awareness during the induction period of
      general anesthesia in which the effects of anesthetics are unstable. METHODS: The
      research-nurses interviewed the patients, who had undergone general anesthesia,
      on the awareness during anesthesia within a week after operation. The patients
      were excluded from the study if they were in deep sedation or unconscious because
      of the medical reasons. We defined the induction period from the administration
      of hypnotic drugs to the tracheal intubation. RESULTS: Seven cases with ages from
      20 s to 70 s out of 1922 cases were identified as the residual awareness cases
      during the induction period. Six cases were managed with low concentrations of
      inhalation anesthetics after injection of intravenous hypnotics. The incidence
      was lower, but not significant, if they were managed with total intravenous
      technique. The BIS values were above 60 in all these cases if the monitor was
      attached. CONCLUSIONS: The incidence of awareness during the induction was 0.36%.
      We have to pay more attention to the disappearance of the hypnotic effect at the
      induction period.

PMID- 15852626
TI  - [Effect of extended paraaortic lymph node dissection on postoperative pancreatic
      function in gynecologic procedures].
AB  - BACKGROUND: We tested a hypothesis that extended gynecological paraaortic lymph
      node dissection seriously impairs postoperative pancreatic function. METHODS: We
      studied 82 patients who underwent gynecologic surgery for malignancy from
      January, 2002 to October, 2003. After scheduled operation, we assigned them to
      one of two groups; patients who underwent extended gynecological paraaortic lymph
      node dissection (n=34) or those who did not (n=48). We measured plasma amylase
      levels in all patients before operation and 1, 3, 7 days after operation.
      RESULTS: Preoperative amylase levels were the same in the two groups. Time
      dependent increases in plasma amylase level were noted in both groups. From 1 to
      3 days after operation, however, plasma amylase levels were significantly higher
      in patients who had undergone paraaortic lymph node dissection than in those who
      had not. Furthermore, lethal postoperative pancreatitis developed in one patient
      who showed marked high levels in plasma amylase level after paraaortic lymph node
      dissection. CONCLUSIONS: Our results suggest that paraaortic lymph node
      dissection in gynecologic operations seriously impairs pancreatic function and
      that one should maintain a high suspicion of postoperative pancreatitis.

PMID- 15852627
TI  - [Comparison of perioperative factors of elective abdominal aortic aneurysm
      surgery and those of ruptured abdominal aortic aneurysm surgery].
AB  - BACKGROUND: Currently the mortality rate of elective abdominal aortic aneurysm
      (eAAA) surgery has improved. However the mortality rate of ruptured abdominal
      aortic aneurysm (rAAA) surgery remains high. We compared perioperative variables
      of eAAA surgery and those of rAAA surgery. METHODS: From 1997 to 2002, 98
      consecutive patients who had undergone graft replacement of infrarenal AAA (56
      eAAA and 42 rAAA) were evaluated retrospectively. RESULTS: Significant
      differences existed between eAAA and rAAAs in following perioperative variables:
      agg (eAAA: 74.2 +/- 6.8 years, rAAA: 74.2 +/- 8.6 years), duration from the
      admission to the time of starting operation (eAAA: 62 +/- 11 min, rAAA: 28 +/- 17
      min), duration from the time of starting operation to the aortic cross clamping
      (eAAA: 87 +/- 29 min, rAAA: 29 +/- 32 min), duration of the aortic cross clamping
      (eAAA:59 +/- 19 min, rAAA: 71 +/- 29 min), blood loss (eAAA: 1297 +/- 1046 ml,
      rAAA: 4619 +/- 4960 ml), total amount of blood products required (eAAA: 1058 +/-
      953 ml, rAAA: 5619 +/- 4945 ml), intensive and/or high care unit stay (eAAA: 1.8
      +/- 1.2 days, rAAA: 6.4 +/- 8.1 days), the postoperative mortality rate (eAAA:
      0%, rAAA: 19%), and postoperative complications (eAAA: 14%, rAAA: 48%),
      CONCLUSIONS: Patients who had undergone rAAA surgery had higher mortality and
      more postoperative complications than those after eAAA surgery. Elective rapair
      before AAA ruptures is recommended.

PMID- 15852628
TI  - [Effects of landiolol hydrochloride on cardiohemodynamics in patients who
      underwent coronary artery bypass grafting].
AB  - BACKGROUND: It is important to control heart rate for coronary artery bypass
      grafting. The purpose of this study was to evaluate the effects of landiolol
      hydrochloride, ultra-short-acting beta-blocker, on cardiohemodynamics in 10
      patients who underwent coronary artery bypass grafting. METHODS: Anesthesia was
      induced and maintained with midazolam and fentanyl. After stabilization of
      anesthesia, landiolol hydrochloride was administered at a rate of 0.04 mg x kg(
      1) x min(-1) for 30 min after 0.125 mg x kg(-1) x min(-1). Hemodynamic
      measurements were made before and every 5 min after administration of landiolol
      hydrochloride. RESULTS: Heart rate decreased significantly although arterial
      pressure was unchanged. There were no changes in cardiac index, left ventricular
      stroke volume index, systemic vascular resistances and pulmonary vascular
      resistance after landiolol hydrochloride administration. CONCLUSIONS: These
      results suggest that landiolol hydrochloride possesses less negative inotropic
      action than negative chronotropic action. Landiolol hydrochloride did not affect
      both systemic and pulmonary vascular resistances because of high
      cardioselectivity.

PMID- 15852629
TI  - [General anesthesia by propofol infusion for delivery by cesarean section
      compared with sevoflurane anesthesia using bispectral index (BIS) monitoring].
AB  - BACKGROUND: We compared the postoperative effects of propofol and sevoflurane
      used for anesthesia during elective cesarean section, using bispectral index
      (BIS) monitoring. METHODS: Fourteen parturients were randomized into two groups
      (Propofol group; P group, Sevoflurane group; S group). All patients received
      thiopental and suxamethonium for induction and had orotracheal intubation in
      rapid sequence. All patients received 1% sevoflurane until delivery. In the P
      group, sevoflurane was stopped after delivery and propofol infusion was started,
      to achieve target BIS values below 60; the infusion rate was 6. 17 +/- 0.98 mg x
      kg(-1) x h(-1). Patients in the S group received 1% sevoflurane. All patients
      were given fentanyl and vecuronium as required. RESULTS: There were no
      significant differences between the two groups in their times for beginning
      drinking, walking, eating or removal of urinary catheters after the operations.
      There were no significant differences in total blood loss or intraoperative dose
      of oxytocin, but postoperative and total doses of oxytocin were significantly
      higher in those in the P group. CONCLUSIONS: Comparing the effects of propofol
      and sevoflurane on the postoperative condition of parturients, no differences
      could be detected. We can choose to use propofol instead of sevoflurane for
      cesarean section.

PMID- 15852630
TI  - [Severe hyponatremia during transurethral resection of prostate].
AB  - We report a case of severe hyponatremia (Na 82 mEq x l(-1)) during transurethral
      resection of the prostate for benign prostatic hypertrophy. A 61-year-old man was
      managed with epidural anesthesia and intravenous propofol. Three percent sorbitol
      (Uromatic S) solution was used for irrigation fluid. The serum sodium level 1 and
      3 hours after the start of operation was 103 mEq x l(-1) and 82 mEq x l(-1),
      respectively. One hour after cessation of propofol administration he did not wake
      up, although he responded to mechanical stimulation. Saline (1.7%) and sodium
      bicarbonate (8.4%) were infused. Thirteen hours after the operation, serum sodium
      level rose to 114 mEq x l(-1), and he opened the eyes on verbal commands. Twenty
      eight hours after the operation, serum sodium level was 132 mEq x l(-1).
      Postoperative neurological deficit did not occur.

PMID- 15852631
TI  - [Perioperative thyroid storm in a patient with undiscovered hyperthyroidism].
AB  - Thyroid storm can develop in patients with longstanding untreated
      hyperthyroidism. It is more often precipitated by an acute event such as surgery,
      trauma, or infection. We experienced a case in whom thyroid storm occurred during
      surgery, while he had no preoperative diagnosis of thyroid disease. A 30-year-old
      man was scheduled for left tympanoplasty. Anesthesia was induced and maintained
      with sevoflurane and nitrous oxide in oxygen. Heart rate and rectal temperature
      went up to 140 beats x min(-1) and 39 degrees C, respectively, in 3 hours during
      surgery. Cooling blanket, cold fluid infusion, flurbiprofen, diltiazem, and
      verapamil were used to decrease body temperature and heart rate. Surgery was
      completed and after emergence he was in agitation for 4 hours along with
      hyperpyrexia and tachycardia. He was diagnosed as hyperthyroidism by
      postoperative physical and laboratory examination. Thiamazole and propranorol
      were administered. In one week, symptom has declined with body temperature and
      heart rate of around 36 degrees C and 90 beats x min(-1), respectively. We should
      be more careful about evaluation of preoperative patients.

PMID- 15852632
TI  - [Management of postoperative pharyngeal swelling after anterio-posterior cervical
      fusion under pharyngoscopy].
AB  - A 47-year-old man with traumatic cervical spinal cord injury underwent anterio
      posterior cervical fusion, which accompanied high-risk of upper airway
      obstruction by postoperative reactive pharyngeal swelling. After the operation,
      we ascertained that he had no paralysis of his extremities, and sedation and
      mechanical ventilation were started at ICU. We evaluated the degree of edema in
      the hypopharyngeal and supraglottic regions with pharyngoscopy. On postoperative
      day 3, the direct fiberoptic evaluation showed postoperative swelling of the
      upper airway. On postoperative day 8, extubation was performed after confirming
      the healing pharyngeal edema by fibroptic evaluation. To achieve successful
      extubation, fibroptic pharyngoscopy should show that the pharynx around the
      endotracheal tube wide enough to see the larynx including epiglottis.
      Pharyngoscopy is a useful method to evaluate the upper airway.

PMID- 15852633
TI  - [Cranial subdural hematoma after inadvertent dural puncture at epidural
      anesthesia].
AB  - Intracranial subdural haematoma has been reported to be an exceptionally rare
      complication of accidental dural puncture. An accidental lumbar dural puncture
      occurred in a 36-yr-old male undergoing orthopedic knee surgery. On the morning
      after the operation, the patient complained of severe occipital headache,
      although this was relieved with loxoprofen and rest. This was assumed to be a
      postdural puncture headache (PDPH) because it had a postural component (it was
      worse on sitting up). On the third day after the operation, the patient developed
      a severe diffuse headache together with nausea, which did not subside with
      analgesia and bed rest. Magnetic resonance imaging of the head showed a small
      acute subdural hematoma in the bilateral temporooccipital region with no mass
      effect. The patient was conscious and oriented. There was no focal neurological
      deficit. The patient was managed conservatively with bed rest and intravenous
      fluids. His condition improved without surgical decompression and was discharged
      on the 40 th day after the operation. Severe and prolonged PDPH shoud be
      considered as a warning sign of an intracranial complication.

PMID- 15852634
TI  - [Conditions under which alveolar air equations are modified and the compensation
      terms of saturated water vapor in those equations].
AB  - Concentration-pressure conversion by a capnometer is confused even now. This
      might be attributed to the fact that the alveolar air equation is defined without
      saturated water vapor. In the present report, alveolar air equations (Riley,
      Filley and a tidal volume residual type) are modified under the condition that
      inspired gas is dry (BTPD) and expired gas is saturated by water vapor (BTPS).
      Consequently only a compensation term of saturated water vapor is simply added to
      the Riley type alveolar air equation, and two terms to the Filley type. The tidal
      volume residual type one is simplified. Modification of the equations enables the
      values of expired volume and expired gas concentration which are measured under
      the above condition to be substituted directly for variables of these equations
      written in the form of concentration.

PMID- 15852635
TI  - [Role of anesthesiologists is the education of cardiopulmonary resuscitation in
      local hospitals].
AB  - BACKGROUND: In Japanese local hospitals there are not many persons who can give
      speedy and exact medical treatment in emergency. We investigated a role of
      anesthesiologists in the education of cardiopulmonary resuscitation (CPR) in
      local hospitals. METHODS: A total of 3 doctors and 30 nurses completed the
      questionnaire about the education of CPR after training of advanced cardiac life
      support (ACLS) in a local hospital. RESULTS: It showed that all doctors and
      nurses have had some anxiety about the emergency treatment of patients and could
      understand the importance of CPR. Moreover, most of them answered that they
      wanted to learn ACLS more, and that the training of ACLS simulation was the most
      impressive. CONCLUSIONS: It is important for anesthesiologists to teach ACLS and
      to promote the spread of ACLS in local hospitals.

PMID- 15852636
TI  - [Critical incidents during regional anesthesia in Japanese Society of
      Anesthesiologists-Certified Training Hospitals: an analysis of responses to the
      annual survey conducted between 1999 and 2002 by the Japanese Society of
      Anesthesiologists].
AB  - BACKGROUND: Recently, a national survey in France including 35,439 patients who
      had received spinal anesthesia showed that the incidences of cardiac arrest and
      mortality associated with spinal anesthesia were 2.5 and 0.8 per 10,000
      anesthetics, respectively. In this study, we investigated these values using data
      obtained from annual surveys conducted by the Japanese Society of
      Anesthesiologist (JSA). METHODS: Since 1994, JSA has conducted annual surveys
      concerning critical incidents in the operating theater by sending confidential
      questionnaires to JSA-certified training hospitals, then collecting and analyzing
      the responses. We investigated critical incidents associated with regional
      anesthesia using data from annual surveys between 1999 and 2002. The
      questionnaire was identical in each survey conducted during these years. The
      total number of anesthetics available for this analysis was 3,855,384, of which
      spinal anesthesia, combined spinal-epidural anesthesia and epidural anesthesia
      were performed in 409,338, 146,282, and 69,001 patients, respectively. In
      patients receiving regional anesthesia, 628 critical incidents including 108
      cardiac arrests, and 45 subsequent deaths were reported. The causes of critical
      incidents were classified as follows: totally attributable to anesthetic
      management, due mainly to intraoperative pathological events, preoperative
      complications, and surgical management. IP consists of coronary ischemia
      including coronary vasospasm not suspected preoperatively, arrhythmias including
      severe bradycardia, pulmonary thromboembolism, and other conditions. Mortality
      was determined by postoperative day 7. Statistical analysis was performed by chi
      square test and Mann-Whitney test. A p value less than 0.05 was considered
      significant. RESULTS: The incidences of cardiac arrest and mortality due to all
      etiologies were 1.69 and 0.76 with spinal anesthesia, 1.78 and 0.68 with combined
      spinal-epidural anesthesia, and 1.88 and 0.58/10,000 anesthetics with epidural
      anesthesia, respectively. The incidences of cardiac arrest and mortality due to
      anesthetic management were 0.54 and 0.02 with spinal anesthesia, 0.55 and 0.00
      with combined spinal-epidural anesthesia, and 0.72 and 0.14/10,000 anesthetics
      with epidural anesthesia, respectively. These values did not significantly differ
      among regional anesthesia. Death attributable to anesthetic management was
      reported in 2 patients: both patients were classified as ASA-PS 3 E, and
      developed cardiac arrest; one due to inadvertent high spinal anesthesia with
      spinal anesthesia, and the other due to local anesthetic intoxication with
      epidural anesthesia. Anesthetic management and intraoperative pathological events
      comprised 33 and 43% of cardiac arrests, respectively. The distribution of causes
      of death was as follows: anesthetic management, 5%; intraoperative pathological
      events, 34%; preoperative complications, 35%; surgical management, 26%. Among the
      causes of anesthetic management-induced critical incidents, inadvertent high
      spinal anesthesia was the leading cause of cardiac arrest in spinal and combined
      spinalepidural anesthesia: 90% of arrests occurred in patients with ASA-PS 1+2;
      88% in patients below 65 years of age; 45 and 25% in patients undergoing hip or
      lower extremities surgery, and cesarean section, respectively. Among the causes
      of intraoperative pathological event-induced critical incidents, pulmonary
      thromboembolism was the leading cause of cardiac arrest in spinal and combined
      spinal-epidural anesthesia: 59% of arrests occurred in patients with ASA-PS 1+2;
      81% in patients above 66 years of age; 91% in patients undergoing hip or lower
      extremity surgery. CONCLUSIONS: The incidence of cardiac arrest and mortality
      associated with spinal anesthesia in Japan was shown to be in the same order as
      in France by analyzing a larger population. In patients with good ASA-PS,
      critical incidents occurred more often under regional anesthesia than under
      general anesthesia. Inadvertent high spinal anesthesia should be carefully
      avoided. We should also pay much attention to subclinical deep vein thrombosis in
      patients who were scheduled for hip or lower extremity surgery, and tourniquet-
      or bone cement-associated pulmonary embolism in these patients.

PMID- 15852637
TI  - [The management for elderly patients with infectious diseases].

PMID- 15852638
TI  - [Aging and DNA methylation].

PMID- 15852639
TI  - [Possible translation of findings in biomedical gerontology into clinical
      practice in geriatrics].

PMID- 15852640
TI  - [Suitable treatment and management for diabetic elderly].

PMID- 15852641
TI  - [Genes for age-related diseases and longevity].

PMID- 15852642
TI  - [Aging and eye diseases].

PMID- 15852643
TI  - [Gender-specific medicine in older women].

PMID- 15852644
TI  - [Associated factors for activities of daily livings in 3 towns in Japan].

PMID- 15852645
TI  - [Community-dwelling elderly in Asian countries].

PMID- 15852646
TI  - [New methods for evaluation of abilities remaining in the elderly with severe
      dementia].
AB  - The elderly with dementia show distinct characteristics and different remaining
      abilities even in advanced disease. For improvement of the quality of care for
      the elderly, it is essential to evaluate their remaining abilities. Mini
      communication Test, Braiding Test and Vitality Index have been developed to
      evaluate the abilities remaining in the elderly with severe dementia. The
      reliability, validity and usefulness of these new methods were discussed.

PMID- 15852647
TI  - [Nutritional factors and functional assessment].

PMID- 15852648
TI  - [The guideline for comprehensive geriatric assessment].

PMID- 15852649
TI  - [Burden felt by family caregivers of the elderly registered with visiting nurses'
      stations in Kyoto].

PMID- 15852650
TI  - [Duties of homehelper in homecare].

PMID- 15852651
TI  - [Role of assistive technology to lighten caregiving burden--dementia care].

PMID- 15852652
TI  - [Caregiver's burden and use of public services among dementia caregivers].

PMID- 15852653
TI  - [Assessment of family caregiver burden in the context of the LTC insurance
      system: J-ZBI and J-ZBI_8].

PMID- 15852654
TI  - [Functional status of very old people in urban area: the Itabashi Oldest-Old
      Study I].
AB  - It is predicted that the future increase in the oldest-old (85 years and older)
      population will have a marked influence on society. However, little is known
      about the features of various functions in the oldest-old. The purpose of this
      study was to clarify the functional status of the oldest-old. We surveyed all
      oldest-old residents in a small area of Itabashi ward in metropolitan Tokyo to
      clarify their living conditions. The oldest-old themselves and their family
      members were invited to participate, and 235 out of 311 residents (75.6%) agreed
      to do so. Forty-two percent of the participants were dependent and needed care
      from others. The ADL status measured by the Barthel Index showed that 30% of
      independent participants also had some deterioration of physical function. These
      results are indicative of increased frailty in the oldest-old. Comparison between
      independent and dependent (need care from others in daily living) showed that the
      functional status was lower in dependent group. However, the psychological well
      being was the same in this two groups. These results indicate progressive
      functional deterioation and psychological adaptation to it, in the oldest-old.
      Further research to elucidate the process of psychological adaptation to frailty
      is necessary in order to promote the well-being among the oldest-old, in whom
      functional limitation is evident.

PMID- 15852655
TI  - [Reliability and validity of a new assessment of the burden on caregivers (ABC
      16)].
AB  - The aim of this study was to evaluate the reliability and validity of a newly
      developed self-administered assessment of the burden on caregivers (ABC-16) in 82
      caregivers (21 men: 61 women, mean age 61 +/- 13 years) including 51 family
      members caring for patients after stroke with physical impairments, and 31 family
      members caring for patents with chronic schizophrenia. The ABC-16 consists of 16
      items and is designed to cover 4 domains (burden of troubles with care receivers,
      burden of loss of social life, financial burden, burden of impairment of
      caregiver's health). The internal consistency was high (alpha=0.854) and
      significant correlations among the four dimensions were found (P < 0.0001).
      Factorial analysis showed 5 latent factors and a multiple regression analysis
      showed the strong correlations between the ABC-16 and care giving during the
      night (P = 0.0045), which strongly suggested excellent validation. The mean and
      standard deviation of the total score of the ABC-16 was 14.66 +/- 7.87 (burden of
      troubles with care receivers; 4.10 +/- 2.36, burden of loss of social life; 4.21
      +/- 2.54, financial burden; 2.93 +/- 2.65, burden of impairment of caregiver's
      health; 3.43 +/- 2.32). The results indicated that the ABC-16 was a tool assess
      care burden with high reliability and validity, and was carried out easily and
      quickly by all participants without complex explains.

PMID- 15852656
TI  - [Cognitive function among physically independent very old people in an urban
      community in Japan: the Itabashi Oldest-Old Study II].
AB  - This study was conducted to clarify the characteristics of cognitive function
      among physically independent very old people dwelling in an urban community in
      Japan. Five hundred and thirteen Old-Old (aged 75-84 years) and 168 Oldest-Old
      (aged 85-100 years) adults participated. We carried out the Mini-Mental State
      Examination (MMSE) for measuring cognitive functions in the elderly. Age-related
      differences in the total score and sub-scale scores of the MMSE were analyzed by
      sex using ANCOVA, controlling for education, vision and hearing problems. Mean
      MMSE scores for Old-Old and Oldest-Old males were 27.53 and 25.88, respectively,
      and those for Old-Old and Oldest-Old females were 27.77 and 24.98, respectively.
      Age-related differences in the MMSE total score between the Old-Old and Oldest
      Old were observed in both sexes, suggesting that overall cognitive functions
      continue to decline over time in very old age. Age-related differences between
      the Old-Old and Oldest-Old in items measuring, registration, calculation and
      delayed recall were observed in both sexes, and in addition, time orientation,
      place orientation, delayed recognition, writing sentences, and copying figures
      were observed in females. These findings suggest that the faculties are those
      most sensitive to normal aging among very old individuals. There were no age
      group differences in five items: reverse spelling, naming objects, repeating a
      sentence, listening and obeying, and reading and obeying.

PMID- 15852657
TI  - [Risk factors for heavy burden among family caregivers in a rural town in
      Hokkaido].
AB  - OBJECTIVE: The present study was conducted in order to investigate risk factors
      for heavy burden of family caregivers. STUDY DESIGN: Cross-sectional study.
      PARTICIPANTS: 51 pairs of the frail elderly and their family caregivers in one
      town in Hokkaido. RESULTS: Compared to those with a lighter burden, family
      caregivers with heavier burden looked after the frail elderly with more behavior
      disturbances due to dementia. They cared for the elderly longer and had less time
      to go out without accompanying their charges than less burdened caregivers. On
      the other hand, the elderly had similar activities of daily living and degree of
      need of care between the two groups. In addition, physical caring time did not
      differ between the two groups. These findings suggest that the psychological
      burden may be more important than the physical burden. In addition, caregivers
      used only 30-40% of services they had the right to use with long-term care
      insurance. These findings suggest that more convenient services for users should
      be provided.

PMID- 15852658
TI  - [The assessment of the reliability and the validity of the EOQOL questionnaire of
      osteoporotics--QOL assessment of elderly osteoporotics by EOQOL].
AB  - We presented a novel and specific questionnaire for quality of life of elderly
      subjects with osteoporosis (EOQOL), and analyzed its reliability and validity.
      Based on the discussions with elderly people of osteoporosis, we extracted key
      words related to complaints of patients with vertebral fractures. A 49
      questionnaire was developed on concepts derived from key words. The
      subdirectories of the questionnaire for elderly osteoporotic subjects consisted
      of pain, daily activity, movement, physiological activity, duty, recreation and
      well-being. To analyze the reliability and the validity of EOQOL, it was
      evaluated in 101 elderly subjects with osteoporosis. Crohnbach's alpha coeffient
      was 0.82 for pain, 0.86 for daily activity, 0.73 for movement, 0.83 for mood,
      0.78 for anxiety against falls, 0.84 for physiological activity, 0.85 for duty,
      0.66 for free time, 0.78 for a nice feeling about life. These results indicated
      that EOQOL is useful as a disease specific questionnaire for elderly osteoporotic
      patients with osteoporosis.

PMID- 15852659
TI  - [A case of lactic acidosis caused by buformin in an oldest elderly diabetic
      patient].
AB  - A 93-year-old male was urgently admitted to our hospital with dyspnea and
      disturbance of consciousness. The patient had been visiting a general physician
      regularly for ten years, for treatment of type 2 diabetes. He had been treated
      with glibenclamide and voglibose, until voglibose was replaced with buformin 3
      months before admission. During pre-admission treatment, his HbA1c was 10-12% and
      serum Cr level was around 2mg/dL, but insulin therapy had never been considered
      because of "being too old". The patient had started taking furosemide one year
      before admission, because of edema of the lower legs, and also spironolactone two
      months before admission. Anorexia had continued for one month before admission on
      May 29, 2003. On admission, his laboratory data were; blood glucose 87mg/dL,
      HbA1c 12.5%, BUN 75mg/dL, Cr 3.9mg/dL, lactate 253.1 mg/dL, and blood gas
      analysis; pH 6.97, anion gap 45.3mmol/L breathing room air, suggesting marked
      lactic acidosis with renal failure. Intensive care with bicarbonate and fluid
      therapy was successful, and his glycemic control improved markedly with insulin.
      On the other hand, his activity of daily living (ADL) severely deteriorated while
      in hospital Home follow-up was therefore not indicated, and he had to change a
      hospital for further follow-up. This case report gives rise to the question of
      how we should manage diabetes in the oldest elderly, including the use of insulin
      and biguanides. In addition, complications of biguanides in the elderly are
      reviewed.

PMID- 15852660
TI  - [A case of an elderly type 2 diabetes who had severe diabetic nephropathy without
      retinopathy].
AB  - We encountered a man who developed severe diabetic nephropathy without
      progression of diabetic retinopathy. He had a 14-year history of diabetes, and
      had been treated with sulfonylurea, and his HbA1c remained around 6.5%. He was
      admitted because of systemic edema and dyspnea on effort Laboratory data revealed
      renal failure and nephrotic syndrome, whereas there was no symptom of diabetic
      retinopathy. Since diabetic nephropathy usually progresses in parallel with
      retinopathy, it is atypical to develop severe nephropathy without retinopathy. In
      this case, longstanding hypertension and his genetic background including
      angiotensin converting enzyme D/I polymorphism might have played an important
      role in development of diabetic nephropathy.

PMID- 15852661
TI  - [Genetic counseling--present status and future trend].

PMID- 15852662
TI  - [Medical virtual reality: an application to surgery simulation].

PMID- 15852663
TI  - Immune tolerance induced by donor antigen and cyclophosphamide in rat fetal small
      bowel transplantation.
AB  - BACKGROUND/PURPOSE: Donor specific immune tolerance is thought to be the ideal
      state for the recipient after organ transplantation. The administration of donor
      antigens and cyclophosphamide has been reported to induce donor specific immune
      tolerance in heart or liver transplantation. However, the effectiveness of this
      method for small bowel transplantation has not yet been studied. We assessed the
      cyclophosphamide induced immune tolerance on rat fetal small bowel
      transplantation. METHODS: Lewis rats (RT1(1), n=99) were used as recipients while
      either F344 (RT1(1), n=44) or WKAM (RT1(u), n=47) rats were used as donors. The
      combination of F344 and Lewis rats produces an immunologically low responder,
      while that of WKAM and Lewis rat produces a high responder. Bone marrow and
      spleen cells were harvested from the donor rats and 3x10(8)/kg of each were
      administrated to the recipient rats intravenously on day 0. Next,
      cyclophosphamide was given either divisionally or bolously. The fetal small bowel
      of the same strain as the donor was transplanted into the rectus muscle of the
      recipient abdominal wall on day 10. On day 17, all grafts were taken out and
      graft survival was thereafter evaluated. The body weight of recipient was also
      assessed. RESULTS: Most of the grafts (87.5%) survived in the F344-Lewis rat (low
      responder) combination using the divisional administration of 120 mg/kg of
      cyclophosphamide. Histologically, most of them showed the whole layers of the
      intestinal architectureto be well preserved. The weight loss of the recipient was
      minimal after divisional administration. In contrast, no graft survived in the
      WKAM-Lewis rat (high responder) combination. CONCLUSIONS: Immune tolerance is
      considered to be induced by the administration of donor specific antigen and
      cyclophosphamide in an immunologically low responder combination. Therefore, this
      method is expected to be useful as an adjuvant therapy and may also be able to
      reduce the dose of immunosuppressive agents in living-related clinical small
      intestinal transplantation.

PMID- 15852664
TI  - A laparoscopic radical prostatectomy assisted by the "ZEUS" robotic system: an
      initial case report.
AB  - A 68-year-old man with prostate cancer, T1cN0M0, was treated with laparoscopic
      radical prostatectomy (LRP) assisted by the ZEUS robotic system. The ZEUS system
      was utilized only for vesico-urethral anastomosis, one of the most difficult
      procedures to perform during LRP. We could complete the vesico-urethral
      anastomosis using the ZEUS system for 100 min without any intraoperative
      complications. The urethral catheter was removed 7 days after operation. To our
      knowledge, this is the initial case of robot-assisted radical prostatectomy using
      the ZEUS system.

PMID- 15852665
TI  - [Usefulness of an all-in-one clinical pathway for transurethral resection of
      prostate].
AB  - We evaluated the usefulness of our original all-in-one clinical pathway for
      transurethral resection of the prostate (TUR-P) on 86 consecutive patients. There
      were 27 consecutive patients treated before introduction of the clinical pathway
      (group 1). Twenty-nine consecutive patients were treated just after the
      introduction of the clinical pathway (group 2) and 30 consecutive patients were
      treated one year after the introduction of the clinical pathway (group 3). Our
      pathway includes all items such as vital sign charts and events charts. Although
      the hospitalization ranged from 5 days to 12 days after introduction of the
      clinical pathway, the average length of hospital stay was shortened by 2.6 days
      in group 3. Although the duration of the postoperative indwelling urethral
      catheter ranged from 2 days to 7 days in the groups 2 and 3, the average duration
      was approximately 4 days in group 3. Postoperative complications did not differ
      among the three groups. The medical insurance claims decreased with the
      introduction of the clinical pathway. Our all-in-one clinical pathway is
      considered to be a good tool for not only reduction of health care costs but also
      giving higher quality and better service to patients.

PMID- 15852666
TI  - [Efficacy of intranasal desmopressin in the treatment of nocturia due to
      nocturnal polyuria].
AB  - Older adults often cite nocturia as one of the most bothersome lower urinary
      tract symptoms (LUTS). We investigated the efficacy and safety of intranasal
      desmopressin in the treatment of nocturia due to nocturnal polyuria on 12
      patients (ten men, two women) ranging in age from 53 to 77 years (mean 67 years).
      All patients experienced more than two episodes of nocturia per night, and had a
      nocturnal urine volume greater than 35% of the daily voided volume, measured
      using a 3-day voiding diary with a frequency-volume chart. They began taking
      intranasal desmopressin (10 microg) at bedtime. When compared with the baseline
      data, the nocturnal urine volume, (928 +/- 307 versus 469 +/- 251 ml, p = 0.0007)
      and nocturnal frequency (4.8 +/- 2.0 versus 2.8 +/- 1.8, p = 0.0009) were
      significantly decreased. The daytime urine volume (1,008 +/- 458 versus 930 +/-
      419 ml, p = 0.49) did not change significantly. The unine osmolarity (420 +/- 143
      versus 598 +/- 158 mOsm/kg, p = 0.0065), and urine sodium levels (100 +/- 32
      versus 140 +/- 60 mEq/l, p = 0.007) increased significantly, whereas the serum
      sodium levels (141 +/- 3 versus 135 +/- 7 mEq/l, p = 0.048) decreased
      significantly. Among the 12 patients, 5 (41.6%) patients reported side effects,
      including headache in 1, edema in 1 and hyponatremia in 3. The patient with edema
      discontinued medication, but the other 4 patients continued their medication and
      the side effects subsided. In conclusion, desmopressin is an effective treatment
      for adult patients complaining of nocturia due to nocturnal polyuria. One should
      be aware of the potential side effects including hyponatremia.

PMID- 15852667
TI  - [Outcome of treatment with surgical resection of the remaining tumor after
      modified M-VAC treatment for advanced urothelial carcinoma].
AB  - We retrospectively evaluated the effect of the surgical resection of the
      remaining tumor after modified M-VAC (methotrexate, vinblastine, doxorubicin and
      cisplatin) (m-M-VAC) treatment for locally advanced or metastatic urothelial
      carcinoma. In m-M-VAC therapy, methotrexate and vinblastine on 15 and 22 days
      were omitted from the classical M-VAC to avoid the discontinuation and the dose
      reduction, and duration of 1 course was shortened to 21 days from 28 days of the
      classical M-VAC. Seven patients with locally invasive or metastatic carcinoma of
      the renal pelvis, ureter, and bladder, 6 males and 1 female, with a median age
      64.1 years, ranging from 49 to 77 years received m-M-VAC chemotherapy without
      severe side effects. In all patients, the residual viable carcinoma was
      completely resected and they achieved complete remission. The median survival
      time was 20 months (range, 7 to 61). Five of these 7 patients were still alive.
      Two patients had no recurrence and achieved long-term survival (survival
      duration; 61 and 39 months). Although further studies and long-term follow up are
      required, these results suggest that patients who present with locally advanced
      or metastatic urothelial carcinoma may benefit from surgical resection after m-M
      VAC.

PMID- 15852668
TI  - [Transurethral resection for prostatic adenoma larger than 100 ml--preoperative
      treatment with interstitial laser coagulation of the prostate plus chlormadinone
      acetate as a treatment maneuver for safer operations].
AB  - Between August 1985 and March 2004, we performed transurethral resection of the
      prostate (TURP) in 18 patients with benign prostatic hyperplasia (BPH) whose
      prostatic volume was larger than 100 ml. We divided the patients into two groups.
      Group A consisted of a total of 14 cases: 10 cases whose mean prostate volume was
      114 ml (100 to 137 ml) and 4 cases whose prostate volume was not measured before
      TURP but whose mean resected prostatic tissue weight was 113 g (105 to 118 g).
      Group B consisted of 4 cases whose mean prostate volume was 110 ml (101 to 133
      ml). Patients in group B underwent interstitial laser coagulation of the prostate
      (ILCP) followed by oral chlormadinone acetate (CMA) therapy (50 mg/day); TURP was
      performed 6 months later, once the prostate volume had shrunk to an average of 76
      ml (66 to 91 ml). Mean resected weights and operation times were: group A, 93.1
      g, 66.3 min; group B, 60.5 g, 55.7 min. There were 12 blood transfusion cases
      (85.7%; intraoperative) in group A, and 1 (25.0%; POD 1) in group B. Accordingly,
      this preoperative treatment was considered a safer method of TURP for BPH 100 ml
      or more. There were no cases of TURP syndrome or death in either group.

PMID- 15852669
TI  - [Active combination immunochemotherapy with interferon-alpha, interleukin-2 and
      gemcitabine for four patients with metastatic renal cell carcinoma].
AB  - Immunochemotherapy consisting of interferon-alpha (IFN-alpha), interleukin-2 (IL
      2), and gemcitabine (GEM) for metastatic renal cell carcinoma. A partial response
      maintained for 15 months, was obtained in one case resistant to IFN-alpha and IL
      2 of para-aortic lymph node metastases (case 1). A minor response with 30%
      reduction of lung metastasis was obtained in one IFN-alpha resistant case, and
      the duration was 6 months (case 2). In one case, in contra-lateral renal
      metastasis, no disease progression was obtained for 6 months (case 3). One case
      with resistance to IFN-alpha and IL-2, and who had preoperative abnormalities of
      corrected serum calcium, serum c-reactive protein and hemoglobin, had progressive
      disease and died of cancer after 6 months (case 4). Grade 3 toxicity was noted in
      leucopenia (4/4), anemia (1/4), and nausea/ vomiting (1/4). Although the response
      duration was short, the combination immunochemotherapy consisting of IFN-alpha,
      IL-2 and GEM may be a promising salvage regimen for the patients with metastatic
      renal cell carcinoma.

PMID- 15852670
TI  - [A case of retroperitoneal liposarcoma arising from the renal capsule].
AB  - We treated a case of retroperitoneal liposarcoma arising from the renal capsule
      by operation and adjuvant radiation. A 61-year-old woman was referred to our
      department for treatment of a right renal tumor revealed by computed tomography
      (CT). CT, magnetic resonance imaging and angiography demonstrated a large renal
      tumor with fat tissue, fed from the renal capsular artery. Right radical
      nephrectomy was performed on February 4, 2003. The tumor was diagnosed
      histopathologically as well differentiated liposarcoma arising from the renal
      capsule. The surgical margin was positive. Therefore, the patient was given 50 Gy
      of radiation postoperatively. There have been only 18 reports of liposarcoma
      arising from the renal capsule in Japan.

PMID- 15852671
TI  - [Treatment with TAE of subcapsular hematoma as a complication of extracorporeal
      shock wave lithotripsy (ESWL): a case report].
AB  - A 58-year-old man with a left renal stone and with poor controlled hypertension
      was attacked by sudden onset of left renal colic pain, gross hematuria and nausea
      at 3 hours after ESWL. Ultrasonography and enhanced computed tomography revealed
      severe subcapsular hematoma, which compressed the left kidney. Since serum
      hemoglobin level continued to decrease in spite of 7 days of conservative
      therapy, we performed transfusion of red blood cells and selective transarterial
      embolization (TAE). Renal angiography showed multiple pseudo-aneurysms of
      arteriole at the lower pole of the left kidney. Embolization of left renal artery
      was effective to relieve patient's symptom and to stabilize the serum hemoglobin
      level.

PMID- 15852672
TI  - [A case of five metachronous primary cancers].
AB  - We report a case of five metachronous primary cancers completely resected during
      39 years. An 80-year-old woman had been diagnosed with and treated for bilateral
      breast cancers, gastric cancer, sigmoid colonic cancer, Bowen's disease and renal
      pelvic cancer. These cancers were found as metachronous cancers and were
      surgically treated. This is the first case of completely resected metachronous
      five cancers in Japan.

PMID- 15852673
TI  - [Malacoplakia in the ureter and bladder].
AB  - We report a case of malacoplakia in the ureter and bladder. A 78-year-old woman
      was admitted to our department for detailed examination of hydronephrosis. A
      small-fingertip-sized tumorous yellowish white lesion was detected by cytoscopy
      at a site that appeared to be the right side of the ureteral orifice.
      Transurethral resection was performed on the same site. Flat yellowish white
      protruding lesions were seen at two sites on the right ureter. Michaelis-Gutmann
      bodies were observed in biopsy specimens from both the bladder and ureter, and a
      diagnosis of malacoplakia was made. Ascorbic acid and bethanechol chloride were
      administered postoperatively. Endoscopy performed three months after the
      operation showed that the protruding lesions in the bladder and ureter had
      disappeared. Narrowing of the ureter or vesicoureteral reflux has not been seen
      to date.

PMID- 15852674
TI  - [Endoscopic treatment for severe encrusted ureteral stent left in place for 3
      years].
AB  - A 52-year-old man had bilateral ureteral stents placed before treatment for
      ureteral and renal stones, but did not return for treatment and follow-up. Three
      years later, he complained of hematuria and vertigo. An abdominal X-ray revealed
      large renal and ureteral stones rising from and enveloping the stent. A bilateral
      percutaneous nephrostomy was placed. The right ureteral stent was easily removed
      with a cystoscope. The left ureteral stone was separated from the stent by
      ureteroscopic lithotripsy (TUL) and percutaneous nephroscopic lithotripsy (PNL).
      The left stent was torn off and difficult to remove because of encrustation. It
      was finally removed through an endoscopic procedure. Right PNL and extracorporeal
      shock wave lithotripsy (ESWL) were performed and all stones and stents were
      extracted. He was stone-free at 4 months.

PMID- 15852675
TI  - [Carcinoma of the urachus: a case report].
AB  - A 34-year-old married woman complaining of macrohematuria was admitted to our
      institute. Cystoscopy revealed a broad-stalk, nonpapillary tumor at the urinary
      bladder dome, and cold-punch biopsy proved it to be a mucus-producing
      adenocarcinoma. Abdominal managnetic resonance imaging demonstrated a tumor
      extending from the umbilicus to the bladder dome, and chest computed tomography
      (CT) demonstrated a small lung tumor with calcification. Examination of the upper
      gostroinstestinal tract, barium enema, and colon fiberscopy did not reveal
      abnormalities. We therefore diagnosed an urachal carcinoma with lung metastases.
      Total cystectomy, umbilical-urachal resection, hysterectomy, ileal neobladder,
      and partial resection of lung were performed, followed by partial resection of
      the left lung using thoracoscopy. About 6 months later, chest CT demonstrated
      multiple metastases in the right lung. After treatment with three courses of
      chemotherapy (paclitaxel and carboplatin), the right lung was partially resected.
      Serum CEA and CA19-9 levels were used to follow her disease, since both were
      elevated before the surgery and at the recurrence. Both indicators returned to
      their normal ranges after treatment. Such cases require careful observation using
      imaging modalities and tumor markers.

PMID- 15852676
TI  - [Urethral recurrence and distant metastases of bladder cancer 9 years after
      cystectomy and neobladder].
AB  - We report a 79-year-old female with urethral recurrence and distant metastases of
      urothelial bladder cancer. She had undergone urethra-sparing cystectomy and
      orthotopic ileal neobladder at 70 years of age. Chemotherapy was not performed
      and the patient died 5 months later. We concluded that long-term follow-up for
      urethral recurrence in women with neobladders was necessary.

PMID- 15852677
TI  - [Giant sarcomatoid carcinoma with spontaneous vesical rupture: a case report].
AB  - A 60-year-old woman has been on steroids under the diagnosis of polymyositis for
      25 years. She was referred to our hospital complaining of asymptomatic
      macroscopic hematuria and lower abdominal pain. Physical examination revealed
      abdominal tenderness and rigidity. We suspected peritonitis because of free air
      image on the abdominal roentogenogram. The computed tomographic (CT) scan
      demonstrated an 8 cm solid mass in the bladder and defect of anterior wall of
      urinary bladder. Then we performed total cystectomy with cutaneous ureterostomy
      and partial resection of ileum as an emergency operation. Macroscopically, intra
      peritoneal bladder rupture and severe adhesion of necrotic bladder dome wall to
      ileum were recognized and the tumor 8 cm in diameter existed in posterior wall of
      urinary bladder. Microscopic examination showed sarcomatoid carcinoma with
      spindle cell component and no invasion to ileum was recognized. Multiple lung,
      liver and bone metastasis appeared 6 months after the operation. She died of
      cancer 11 months after the operation.

PMID- 15852678
TI  - [Inverted papilloma of urinary bladder in two patients with urination difficulty
      as initial symptom].
AB  - We report two men with inverted papilloma of urinary bladder with urination
      difficulty as initial symptom. One was 51 years old and the other was 60 years
      old. Ultrasound revealed a tumor in the bladder and cystoscopy revealed a smooth
      surfaced tumor with a stalk at the bladder trigon. They underwent transurethral
      resection of the bladder tumor and histopathological findings were consistent
      with inverted papilloma. Postoperatively, they are free of urination difficulty
      and have had no recurrence for 3 and 1 years, respectively.

PMID- 15852679
TI  - Pure prostatic papillary adenocarcinoma with ductal features.
AB  - Papillary adenocarcinoma resembling ductal carcinoma and arising in the
      peripheral zone is extremely rare. We report a case of prostatic papillary
      adenocarcinoma with ductal features. The patient was a 68-year-old man who
      initially presented with dysuria and sensation of residual urine after voiding.
      Prostatic needle biopsy findings supported pathological diagnosis of prostatitis.
      The symptoms were improved by medication for prostatitis, and prostate-specific
      antigen (PSA) level of 22.6 ng/ml descreased to 9.9 ng/ml. It remained between
      7.2 ng/ml and 9.9 ng/ml for 2 years. However, it gradually increased to 11.9
      ng/ml. Transrectal digital examination, T2-weighted magnetic resonance imaging
      (MRI) of the prostate and transrecral ultrasound showed a mass in the enlarged
      right side of the prostate. Transrectal needle biopsy of the mass was performed,
      and papillary adenocarcinoma was suspected by histological examination. Radical
      prostatectomy was performed. Histological and immunohistochemical examination of
      the prostatectomy specimen revealed pure prostatic papillary adenocarcinoma with
      ductal features.

PMID- 15852680
TI  - Successful recovery from interstitial pneumonitis, induced by bicalutamide and
      leuprorelin acetate given as treatment for prostate cancer.
AB  - We report a case of interstitial pneumonitis induced by bicalutamide and/or
      leuprorelin acetate given as therapy for prostate cancer, in which the
      pneumonitis was successfully managed by steroid treatment. Steroids were given
      promptly on the day following onset of pneumonitis, and the patient (72 years
      old) recovered almost completely within one and a half months. Interstitial
      pneumonitis, induced by hormone treatment given for prostate cancer, is a
      reversible condition and a quick diagnosis followed by prompt, proper treatment
      is important to ensure a successful recovery. The patient had been free of
      interstitial pneumonitis for 14 months, but died of pneumothorax.

PMID- 15852681
TI  - [Clinical equivalence trial of UROCALUN miniaturized tablet in patients with
      upper urinary tract stone disease].
AB  - We performed a clinical trial on patients with upper urinary tract stone disease
      (renal stone disease) to prove the clinical equivalence as the target for removal
      of renal stones between the new formulation (miniaturized tablet) and the
      conventional formulation (capsule) of UROCALUN. The clinically effective rate of
      both formulations was the same at 70% (28 of 40 cases), and it was suggested that
      these two formulations possess the same clinical efficacy. Adverse drug reactions
      were observed in 10.0% (4 of 40 cases) with the tablet and 5.0% (2 of 40 cases)
      with the capsule. There were no significant differences between the two
      formulations in the incidence of adverse drug reactions, and there were no
      clinically significant safety problems. In the questionnaire survey for patients
      about medication compliance, we found that the patients felt the miniaturized
      tablets were much easier to swallow than the conventional formulation. In
      conclusion, it is suggested that the miniaturized tablet contributes to improve
      the medication compliance for patients and thus it is expected to improve the
      clinical efficacy.

PMID- 15852682
TI  - [Evaluation of forklift trucks operated in dockyards for reducing exposure to
      whole-body vibration].
AB  - Our preceding study revealed that many fork-lift truck drivers in Japanese
      dockyards suffer from fatigue symptoms such as low back pain (LBP). It has been
      suggested that exposure to whole-body vibration (WBV) is a cause of their LBP.
      Using forklift models manufactured from 1982 to 2000, we measured and evaluated
      the vibration of forklift trucks operated in dockyards, adopting experimental
      procedures based on the European Standard. We investigated various factors
      related to WBV, with the main focus on attenuating seat vibration. This study
      showed that (1) the seats did not attenuate vibration in the vertical direction,
      (2) forklift trucks and their seats had not improved in terms of WBV attenuation
      for a decade, (3) some forklift trucks in which the seat suspension could no
      longer be adjusted to the driver's weight continued to be used without being
      repaired, and impractical seat adjustment methods were adopted, and (4) the seats
      did not attenuate vertical vibration well in the most undesirable frequency
      range. We conclude that forklift trucks and especially their seats should
      urgently be improved with regard to WBV attenuation in order to prevent LBP in
      forklift truck drivers.

PMID- 15852683
TI  - [Assessment of the railway workers showing Brugada type electrocardiogram in the
      regular medical checkup].

PMID- 15852684
TI  - [The state and results of countermeasures for mental health at a certain apparel
      company].
AB  - We speculated that there would be more occupational stress in an apparel company
      than in other areas of business, because employees work long hours and under poor
      conditions. We investigated 66 employees of an apparel company who visited an
      occupational physician to consult about their mental health. There were 561 male
      and 387 female employees in that company. The employees who had visited an
      occupational physician had worked long every day under poor conditions, and they
      had been required to be more artistic than other employees in that company.
      Female employees visited occupational physicians more than males. Apparel
      companies, use a system of "specialty store retailer of Private-label Apparel
      (SPA)", and several sections make special trademark "brands". These sections
      compete with each other. Employees must plan, design, make patterns, and sew new
      dresses in a 7-day cycle. They are extremely busy and this therefore creates
      stress. We came to the conclusion that many apparel companies were stressful
      workplaces. It is important that a psychiatrist examines employees who
      occupational physicians have diagnosed as unhealthy. Frequent consultation with
      occupational physicians is as important as a psychiatrists examination. Managers
      must manage absence, efficiency, and written correspondence of all employees.
      These are useful signs of mental disorder. When employees return to work after
      sick leave, rehabilitation in the workplace after absence is useful. The employee
      should work for only two hours a day at first. Working hours are then extended
      gradually. The employee can then return to work easily if this rehabilitation
      program is followed.

PMID- 15852686
TI  - Fortune 1,000 ranked within industries. Health care.

PMID- 15852685
TI  - Doesn't anyone know how to run a drug company?

PMID- 15852687
TI  - Fortune 1,000 ranked within industries. Insurance: life and health.

PMID- 15852688
TI  - Fortune 1,000 ranked within industries. Medical products and equipment.

PMID- 15852689
TI  - Fortune 1,000 ranked within industries. Pharmaceuticals.

PMID- 15852690
TI  - Plans push IT. With an eye to the future, three very different health plan
      organizations look to a new generation of information management solutions.

PMID- 15852691
TI  - Integration and automation transform medication administration safety. Successful
      eMars mandate a multifold integration strategy that includes people, process,
      applications and technology.

PMID- 15852692
TI  - Maximizing the gains of mobility. Mobile technology's workflow improvements for
      physicians have a downstream effect throughout entire healthcare systems.

PMID- 15852693
TI  - Credentialing software: the ayes have it! Pennsylvania eye clinic uses
      credentialing software to improve accounts receivable.

PMID- 15852694
TI  - Healthcare sweeps across the plains.

PMID- 15852695
TI  - The five foundations of successful e-prescribing programs. The right combination
      of technology, people, process and commitment drive success for electronic
      prescribing.

PMID- 15852696
TI  - Music to call center manager's ears. Software distribution reduces management and
      desktop support costs, while providing agents with fast, flexible and dependable
      systems.

PMID- 15852697
TI  - Recovering buried revenue potential. New Hampshire Medical Center deploys
      document management solution that attracts at-home coders and enables reduction
      of unbilled days.

PMID- 15852698
TI  - Meeting the future without paper. Midwest specialty medical group deinstalls a
      disappointing EMR, but adopts new technology to still create a computerized chart
      in a paperless environment.

PMID- 15852699
TI  - Quality as a passion.
AB  - CIGNA Senior Vice President and Chief Clinical Officer W. Allen Schaffer, M.D.,
      describes how a national health plan combines IT and human resources, and
      embraces national evidence-based standards, to influence the individual health
      status of millions of members.

PMID- 15852700
TI  - Health plans & technology hotlist.

PMID- 15852701
TI  - Next-generation health plans: managing the customer experience.

PMID- 15852702
TI  - [Occupational hazard evaluation in exposure to pesticides].
AB  - In the world there are several models of occupational hazard evaluation in
      exposure to pesticides, including the German calculation model as the most
      popular one. Natural investigations in Russia have not confirmed the basic idea
      of the German model, according to which there is a direct relation between the
      amount of active pesticide ingredient and the exposure of an operator to it. The
      use of Russian model implies establishing actual pesticide exposures and
      correlating them with hygienic regulations.

PMID- 15852704
TI  - [Hygienic aspects of forming a healthy lifestyle in Russian Federation].
AB  - The existing system of motivating the population of Russian Federation to lead a
      healthy lifestyle is insufficient. The authors substantiate the necessity of a
      strategy of forming a healthy lifestyle which would be based on the analysis of
      hygienic features of problem situations concerning health and the environment
      (regional differences are taken into account). The strategy should fulfill
      collective- and individual-directed propagandistic programs with broad
      application of modern informational and propagandistic techniques under the
      leadership of Russian Ministry of Health, which is considered to be one of
      priority directions in active motivation towards a healthy lifestyle.

PMID- 15852703
TI  - [The mutagenic and carcinogenic activity of chemical compounds].
AB  - The article presents data on the association between the mutagenicity and
      carcinogenicity of chemical compounds. Genotoxic carcinogens, which universally
      act via interaction with DNA, are positive in tests for mutagenicity. The
      mechanisms of the carcinogenicity of non-genotoxic carcinogens include promotion,
      cytotoxicity and oxidative stress. As mutagenicity tests do not allow
      determination the carcinogenicity of chemical substances, long-term experiments
      on rodents should be considerred the only reliable method of carcinogenicity
      detection.

PMID- 15852705
TI  - [Hygienic aspects of size correction of sanitary-hygienic zones of contemporary
      industrials and other objects].
AB  - The creation and organization of sanitary-hygienic zones plays a significant role
      in diminishing technological pressing on residents of industrialized cities.
      There are three positions that may be considered in connection with this problem.
      The first one consists in deflating the size of a sanitary-hygienic zone together
      with substantiated modifications in the conventional production classification
      for industrials which apply nature-conservative technology. The second position
      implies that the size of a sanitary-hygienic zone should be determined by the
      industrial with the greatest technological pressing on the atmosphere among those
      going to be situated in the given territory. The third position implies that
      large industrial complexes must find financial resources to systematically
      modernize their technological equipment and introduce effective nature
      conservative constructions to diminish the intensity and spread of pollutants in
      the atmosphere. The question of sanitary-hygienic zones along the reservoir banks
      is also topical.

PMID- 15852706
TI  - [Present-day problems of complex hygienic evaluation of drinking water use].
AB  - The authors offer substantiated methodical approaches to complex evaluation of
      the sanitary reliability of drinking water supply systems. They recommend not
      only evaluating drinking water quality, but also assessing the sanitary state of
      water sources (catchment areas), the reliability of water preparation and
      transportation, the standards of water supply and the reliability of production
      laboratory control. A range of complex hygienic studies have demonstrated that
      the problems of Voronezh interurban reservoir as a water source are caused by its
      multi-purpose use. Under these conditions insufficient hygienic efficiency of the
      conventional water preparation schemes and low sanitary reliability of water
      transportation systems favors negative influence of water factor on population
      mortality. The offered methodical approaches give the systematic idea of factors
      that determine drinking water quality. Operative administrative decisions
      concerning hygienic safety of public water use may be made with these methodical
      approaches taken into consideration.

PMID- 15852707
TI  - [Hygienic problems of population health maintenance under the extremal conditions
      of North].
AB  - A range of multi-sided studies, carried out in various regions of Far North
      (Jamalo-Nenets autonomous region, Komi republic, Sakha republic (Yakutia)) have
      established the leading hygienic risk factors of population health deterioration,
      including those characteristic of small nationalities of North. The consideration
      of the obtained data, including regional alimentary status peculiarities, the
      condition of metabolic processes and antioxidant balance of the organism, allowed
      establishment of effective approaches to the maintenance of notherners' health.
      These approaches are based upon the optimization of nutrition as an element of
      population health control under extremal conditions.

PMID- 15852708
TI  - [Hygienic ranking of basic professions in metallurgical industry according to
      labor conditions and state of health].
AB  - In order to establish priorities in health-improving programs the researchers
      analyzed the hygienic situation at Novolipetsk metallurgical complex and ranked
      its technological divisions according to labor conditions of 73 basic professions
      and state of health of the workers engaged to agglomeration works (AW), chemical
      recovery works (CRW), plate rolling (PR) and the workers of a blast-furnace shop
      (BFS) and an oxygen-converter shop (OCS-I and OSC-II).

PMID- 15852709
TI  - [Contemporary laboratory markers of early stages of vibratory pathology
      development].
AB  - Having analyzed literature data and results of their own research, the authors
      describe early alterations on the cellular and molecular levels of the organism
      in exposure to local and general vibration. Those include changes in oxidative
      metabolism, immune shifts, lesions of cell membranes, deterioration of blood
      rheology, lesions of muscular and connecting tissues, disturbances of mineral
      exchange. The paper suggests a complex of laboratory tests for early detection of
      prepathological conditions of the organism in exposure to vibration. It includes
      measurement of certain parameters, such as the serum levels of vitamin E, malonic
      dialdehyde, immunoglobulins IgA, IgM, IgG, circulating immune complexes as well
      as assessment of antioxidative activity, peroxide erythrocyte hemolysis,
      spontaneous and ADF-induced thrombocyte aggregation, measurement of erythrocyte
      diameter and volume, creatinine and oxiproline urine concentration, myoglobine
      blood level and copper serum level. The above parameters are of sufficiently high
      diagnostic sensitivity and reflect the main aspects of vibratory pathology
      pathogenesis.

PMID- 15852710
TI  - [Industrial aerosols are a risk factor of oncologic diseases in underground
      miners].
AB  - The paper contains new data on the carcinogenicity of industrial aerosol to
      miners engaged to underground extraction of sulphide copper and nickel ores.
      Earlier appearance of oncologic diseases (lung and stomach cancer) is typical of
      this category of workers, exposed to higher aerogenic concentration of nickel in
      mine atmosphere. This fact demonstrates that the leading role in the ethiology of
      these diseases is played by multicomponent industrial aerosol containing nickel
      in the form of complex sulphides.

PMID- 15852711
TI  - [Antioxidant and microelement status of the organism: present-day diagnostic
      problems].
AB  - The paper presents methodical approaches to non-invasive biological testing,
      based upon the found correlations between the parameters of the microelement
      status and the intensity of free radical oxidation processes in human alveolar
      moisture. The study demonstrates that the ratio of microelements with close
      chemical properties that display high biological activity and are key environment
      pollutants plays a prognostic role in the organism homeostasis.

PMID- 15852712
TI  - [The epidemiology, risk factors and present-day aspects of allergic disease
      prevention in an industrial center].
AB  - The article is dedicated to the topical problem of allergic diseases in various
      population groups of a large industrial region of Moscow suburb, and presents a
      brief review of present-day epidemiological data on allergic pathology prevalence
      as well as authors' own data on the morbidity of bronchial asthma, allergic
      dermatoses, and allergic rhinitis. The paper also contains the results of an
      analysis of allergic pathology dynamics within 5 to 10 years, and a retrospective
      analysis of allergic pathology structure in adolescents. The researchers
      undertook a multifactor analysis of population habitat in the town Mitishchy,
      based upon ecological and hygienic data concerning atmospheric air and water
      composition. The study points to the role played by industrial environment in the
      appearance of allergic skin diseases. Complex measures on allergic disease
      prevention are considered, and an effective pathogenically grounded method of
      ozonotherapy is suggested as one of prospective non-drug means of treatment.

PMID- 15852713
TI  - [Occupational hazads in metal mining industry].
AB  - Miners of basic professions employed in contemporary metal mining industry are
      exposed to a range of industrial factors, such as vibration, noise, dustiness,
      and unfavorable microclimate. Long-term exposure to these factors is hazardous to
      their health, which is manifested by elevated general and occupational morbidity
      and a higher rate of biological aging. This is most typical of Far North miners,
      who are exposed to the combination of the industrial factors and extremal climate
      and geographic conditions. Research into the health status of miners engaged to
      underground works and open excavations in regions with contrasting climate and
      geographic conditions, allowed determination of main industrial risk factors
      (vibration and noise), leading occupational diseases and groups of high risk of
      their development (according to the occupation and the length of service). The
      study found high risk of cardivascular diseases as well as pathology of the
      musculoskeletal system, which was highest in miners in Norilsk region.

PMID- 15852714
TI  - [Hygienic aspects of health hazards at school age].
AB  - The researchers have developed a method of qualitative and quantitative
      evaluation of risk factors in various types of educational institution. The use
      of this method in the system of social-and-hygienic monitoring makes it possible
      to take into account a greater number of objects of vital activity environment,
      objectively characterize factors of vital activity environment that are hazardous
      to schoolchildren, and determine the order and extent of necessary preventive
      measures. Use of computer techniques in hygienic investigations promotes early
      prenosological diagnostics of school-age conditions that develop under the
      influence of factors of vital activity environment, and allows their timely
      correction.

PMID- 15852715
TI  - [Topical problems of health protection in childhood and juvenile age in relation
      to forming cadre workers' labor longevity].
AB  - Complex investigations of worker-training process have revealed that priority
      within the process of choosing professon and vocational training is not given to
      hygienic problems concerning health of workers to be. The main stages of training
      do not have a common hygienic goal of improving health of workers to be and
      making their professional work more reliable. The authors substantiate the
      necessity for creating a common vocational training system based upon system
      analysis principles and providing for the consistent maintenance and improvement
      of students' health throughout the training process, including such stages as
      vocational guidance, vocational selection and training, to prolong professional
      longevity of qualified workers.

PMID- 15852716
TI  - [Hygienic assessment of the immunobiochemical status of children of Far North
      aboriginal nationalities].
AB  - The study covers the influence of tuition, dwelling and nutrition conditions in
      boarding school on metabolism and immunity of pupils during the initial and final
      stage of tuition. The actual dietary intake in boarding school was found to have
      a carbohydrate bias and be short of micronutrients. The study established age
      specific and regional peculiarities of immunological and biochemical parameters
      of schoolchildren's health status in Far North. The authors conclude that the
      alteration of metabolism typical of arctic aborigines is not genetically
      determined, but is observed as a result of ontogenesis. The study revealed
      alimentary-dependent changes in biochemical parameters of lipid, mineral and
      vitamin exchange. The results show that arctic children experience adaptive
      exertion and immunity alteration due to the change of living stereotype and the
      character of nutrition.

PMID- 15852717
TI  - [Present-day hygienic aspects of dealing with industrial and consumption waste].
AB  - The article covers scientific hygienic positions in forming and solving the acute
      scientific and technical problem of dealing with waste. The given problem is
      topical due to growing amount and diversity of waste and relatively small
      knowledge of ecological, medical and biological aspects of the problem. The paper
      covers the entire "life cycle" of waste, chiefly industrial and communal, as the
      most diverse and potentially dangerous to the environment. Special attention is
      paid to neutralization and recycling of waste for its application as secondary
      material in various branches of national economy. Having critically analized the
      results of complex studies, the authors conclude the article with outlining the
      prospective tasks of research for scientific and practical institutions of
      sanitary surveillance of Russian Federation Ministry of Health.

PMID- 15852718
TI  - [Methodical approaches to evaluation of the safety of veterinary preparation
      application].
AB  - Evaluation of toxicologic hazards associated with the use of veterinary
      preparations against ecto- and endoparasites of animals and poultry with the
      purpose of prophylaxis and treatment, evaluation of industrial safety and
      determination of the upper limits of their residue in live-stock products and the
      environment, underlies protection of population's and operators' health from the
      effects of the drugs. The article shows the difference between the acute toxicity
      parameters of cypermethrin isomers and demonstrates that they enter the organism
      chiefly through the skin.

PMID- 15852719
TI  - Histological classification of lung cancer.
AB  - A histological classification should provide guidelines for tumor diagnosis in
      order to evaluate patient prognosis and therapy. Pre-invasive lesions identified
      as precursors of invasive lung carcinoma are: squamous dysplasia/carcinoma in
      situ, atypical adenomatous hyperplasia and idiopatic pulmonary neuroendocrine
      cell hyperplasia. Squamous carcinoma and adenocarcinoma are the commonest types
      of lung carcinoma with the latter increasing in many countries mainly for changed
      smoking habits. Bronchioloalveolar carcinomas include exclusively noninvasive
      mucinous or non-mucinous tumors. Neuroendocrine tumors range from well
      differentiated neuroendocrine carcinoma (typical carcinoid) to intermediate grade
      (atypical carcinoma) to very aggressive poorly differentiated lesions (large cell
      neuroendocrine carcinoma and small cell carcinoma).

PMID- 15852720
TI  - Cytologic diagnosis of pulmonary lesions.
AB  - The major types of cytologic preparations used in most laboratories to detect the
      lesions of the lower respiratory tract (LRT) are examined. These methods include
      sputum, bronchial washing, bronchial brushing, bronchoalveolar lavage (BAL) and
      fine-needle aspiration biopsy (FNAB). Sputum represents the simplest and most
      cost-effective sampling method even though fiberoptic bronchoscopy and radiologic
      guided FNAB are superseding it as the first diagnostic choice in most cases.
      There are advantages and disadvantages associated with each technique:bronchial
      brushing and FNABs tend to preserve both the cellular details and their
      architectural arrangement whereas sputum and bronchial washing often cause a
      variable degree of cellular degeneration and fragmentation. As a result, most
      pulmonary lesions may be detected and correctly diagnosed if multiple techniques
      are used to acquire diagnostic material. CT-guided FNAB represents the most
      effective method to achieve a correct diagnosis in pulmonary tumors.

PMID- 15852721
TI  - Noninvasive staging of lung cancer.
AB  - Accurate evaluation of disease extent is mandatory when the diagnosis of
      resectable lung cancer is established. Staging has a significant impact on
      subsequent therapeutic options and prognosis. Radiologists can now rely on
      numerous instruments, each with different advantages and limitations. The
      procedure of choice is still chest X-ray whose intrinsic limitations require
      better tumor characterization with chest CT. CT difficulties in the differential
      diagnosis between the tumor and secondary changes occurring in adjacent
      structures can be overcome by 18F-FDG-PET or MRI. Functional information is
      acquired with the former and multiparametric information with the latter.
      According to the case, further extension to adjacent structures can be evaluated
      based on CT or MRI. For lymph node and distant metastasis PET is increasingly
      used, except for brain parenchyma where MRI is definitely more accurate in the
      detection of brain metastasis.

PMID- 15852722
TI  - Tnm independent prognostic factors in lung cancer.
AB  - Large studies have demonstrated that TNM staging system is the most consistent
      prognostic factor in patients with non small cell lung carcinoma. However,
      because patients within the same stage may have very different survival, better
      prognostic information is needed. The recent progress in molecular biology has
      allowed the analysis of proteins and genes involved in cancer development. To
      date, more than 150 different prognostic factors affecting survival in patients
      with lung cancer have been discovered and extensively studied. Despite the
      encouraging prognostic results in angiogenesis markers, there is not yet a
      molecular marker validated in large prospective trials that has major independent
      predictive prognostic value.

PMID- 15852723
TI  - Lung cancer screening with spiral CT.
AB  - Lung cancer is the main cause of death from malignancies due to the high
      prevalence and adverse prognosis when diagnosis is established in symptomatic
      patients. With early diagnosis, survival is far better; this led to perform some
      trials of screening in subjects at high risk with chest X-ray since 1970 but
      outcomes were contrasting. The technological evolution with the introduction of
      spiral CT and low dose techniques in the last decade led to a new interest in
      lung cancer screening. Numerous trials were performed and several diagnostic
      algorithms based on the dimensional and densitometric analysis of CT-evidenced
      nodules were designed. In spite of the encouraging outcome achieved so far, the
      high rate of false positives, the high costs and the use of ionizing radiation
      advise caution at least until a decreased mortality rate from lung cancer is
      evidenced.

PMID- 15852724
TI  - The PRE.DI.CA. project for radiographic lung cancer screening in cigarette
      smokers.
AB  - In heavy cigarette smokers and former smokers who have accumulated a high risk of
      lung carcinoma, a primary objective is early detection. Annual chest x-ray
      screening is a readily available, low cost method to detect asymptomatic lung
      carcinoma at an early stage (stage I) and, after radical resection, to improve
      the 5-year survival rate. A project of annual chest x-ray screening, named
      PRE.DI.CA. was started, for the early diagnosis of asymptomatic lung cancer in
      the high risk population of heavy cigarette smokers and former smokers, males and
      females, aged 45-75 years, in the province of Varese. Over a 7-year period, 4.598
      heavy smokers enrolled in the PRE.DI.CA. lung project underwent 14.461 chest x
      ray examinations. 45 asymptomatic lung cancers were detected and defined
      histologically. In the province of Varese it was possible to establish early
      diagnosis of lung carcinoma with annual chest x-ray screening of asymptomatic
      high risk smokers. 52% stage I diagnosis was achieved at the incidence screening.

PMID- 15852725
TI  - Resection of small indeterminate lung nodules by video-assisted thoracoscopic
      surgery (VTS). Implications for the early diagnosis of lung cancer.
AB  - Small indeterminate lung nodules are increasingly detected because of the
      extensive use of chest x-rays and of computed tomography scans. In evaluating a
      small solitary pulmonary nodule the main concern is whether the nodule is benign
      or malignant. Resection by video-assisted thoracic surgery is the standard
      treatment for solitary pulmonary nodules, especially if they are small and not
      accessible by bronchoscopy or by percutaneous transthoracic needle aspiration. In
      this prospective study the personal experience in the diagnosis and treatment of
      lung nodules by video-assisted thoracic surgery and its implications in early
      diagnosis of lung cancer, are illustrated In the reported series video-assisted
      lung wedge resection was carried out successfully in (94%) of lung nodules, with
      low morbidity and no mortality. A definitive pathologic diagnosis was achieved in
      all cases. These findings indicate that indeterminate lung nodules > 1 cm in
      diameter have a high probability (65%) of being malignant and therefore need to
      be resected to establish a definitive diagnosis.

PMID- 15852726
TI  - Preoperative evaluation and risk factors in patients undergoing lung resection
      for cancer.
AB  - Surgical resection remains the mainstay of treatment in lung cancer patients.
      Stratification of preoperative risk should be based on the functional status of
      pulmonary and cardiac systems usually damaged by cigarette smoking. Preoperative
      pulmonary evaluation should be performed taking into consideration the specific
      characteristics of the single patient and the type of surgery planned. Spirometry
      only may be required or oxygen consumption determination is necessary. Cardiac
      assessment should be based on clinical and instrumental examinations while
      invasive tests should be limited to high-risk patients. The potential
      difficulties in endotracheal intubation and lung isolation, the risk for
      desaturation during one-lung ventilation, and postoperative pain control should
      be analyzed.

PMID- 15852727
TI  - Preoperative assessment and risk factors in the surgical treatment of lung
      cancer: the role of age.
AB  - The incidence of lung cancer in the elderly is increasing in Western countries.
      This disease represents the second leading cause of cancer death in this age
      group and it is also responsible for a substantial increment in morbidity and
      health care costs. Several studies suggested that age per se should not be
      considered a risk factor for surgical mortality and morbidity in lung cancer
      patients and access to surgical treatment should not be denied only on the basis
      of age. Indeed, advanced age may represent an indicator of several factors such
      as comorbidity or poor physical performance which in turn can increase surgical
      risk and dramatically reduce life expectancy. Therefore, a careful preoperative
      assessment of these factors, with particular regard to comorbid conditions (such
      as cardiovascular and pulmonary diseases or secondary malignancy) is necessary in
      older adults. In consideration of the need of a multidisciplinary assessment to
      identify comorbidities and operative risk a close collaboration between
      pneumologists, radiologists, oncologists, thoracic surgeons, anesthesiologists,
      cardiologists, geriatric specialists, physical therapists is highly recommended.

PMID- 15852728
TI  - Pneumonectomy for lung cancer: technical and general aspects.
AB  - The current role and technical aspects of pneumonectomy for the treatment of lung
      cancer are evaluated based on the personal experience and on the review of the
      international literature. Over a four-year period 669 operations for lung cancer
      were performed. Fifty-nine were pneumonectomies 11 of which were completion
      pneumonectomies and 7 tracheal sleeve right pneumonectomies 5 of which performed
      with the anesthesiological tube always kept in trachea. Overall postoperative
      mortality was about 10% for pneumonectomy, and about 16,6 % for completion
      pneumonectomy with a median survival rate of 21 and 26 months respectively. In
      agreement with reports of the international literature, it is confirmed that
      pneumonectomy is a high-risk thoracic surgical procedure and an accurate
      cardiovascular and respiratory evaluation is very important for patient
      selection.

PMID- 15852730
TI  - Surgical treatment of non-small cell lung cancer: mediastinal lymph node
      dissection.
AB  - The effectiveness of lymph node dissection in the treatment of non-small cell
      lung cancer is evaluated. The extent of lymphadenectomy in the treatment of NSCLC
      is still controversial. Although some centers perform only mediastinal lymph node
      sampling with resection of suspicious lymph nodes, others recommend radical,
      systematic mediastinal lymph node dissection to improve survival and achieve a
      better staging. Reports of the literature on the subject are reviewed and the
      results achieved with the various procedures are analyzed. A personal technique
      to perform mediastinal lymph node dissection is described.

PMID- 15852729
TI  - Chest wall reconstruction after resection in lung cancer: personal experience.
AB  - Chest wall reconstruction after resection, for locally advanced lung cancer but
      also for some selected secondary tumors, is a demanding challenge to surgeons,
      anesthetists and experts in respiratory function rehabilitation who must
      guarantee a regular natural ventilation, adequate protection of intrathoracic
      organs and acceptable cosmetic outcome. To this aim, many procedures using
      autologous, heterologous, or prosthetic materials, are available. A study
      conducted on 13 lung cancer patients who after resection underwent reconstruction
      with heterologous prosthetic material is presented. No intraoperative mortality
      or septic complications were observed. There was prompt wall stabilization in 10
      patients; it occurred 3 weeks later in another patient (polytetrafluoridethylene
      patch). Only in one patient (prolene mesh) a seroma developed, treated with US
      guided drainage. In the authors' experience, even for fairly small defects
      reconstruction with prosthetic material is suitable, to prevent, in case of the
      presence of risk factors, pulmonary hernia-induced major respiratory symptoms.
      Prosthetic materials are also preferred for benign lesions characterized by a
      long-term survival.

PMID- 15852731
TI  - Pulmonary rehabilitation: pre-and postoperative treatment.
AB  - Lung cancer is the leading cause of cancer-related death in women and men in the
      United States. Since 1987, mortality due to lung cancer surpassed death caused by
      breast cancer in women. Equally discouraging is the fact that survival at five
      years for all lung cancer patients is only 15%. Despite improved survival in many
      patients with early disease, the vast majority suffer from significant morbidity
      and early death. Therefore, proper management of these patients is extremely
      challenging and requires the utmost collaboration between many different
      specialties. In lung cancer patients, pulmonary rehabilitation lowers the risk of
      postoperative complications and reduces the length of hospital stay. At the same
      time, exercise tolerance is improved, anxiety and depression are controlled, thus
      improving the quality of life. Even though quality of life is commonly overlooked
      when treating lung cancer patients, studies have demonstrated that better quality
      of life is a priority for these patients.

PMID- 15852732
TI  - Adjuvant chemotherapy in resected non-small cell lung cancer.
AB  - There is still a high mortality ratio in completely resected non-small cell lung
      cancer patients either due to local or, more often, to metastatic recurrence. The
      NSCLC Collaborative Group Meta-analysis demonstrated a not statistically
      significant advantage in patients treated with cisplatin-based regimens. Many
      subsequent trials were unable to demonstrate the real effectiveness of cisplatin
      based adjuvant chemotherapy with a significant rate of toxicity. The IALT trial
      demonstrated little advantage in overall and disease-free survival with
      acceptable toxicity. A recent meta-analysis of trials including 5716 patients
      demonstrated the role of cisplatin-based chemotherapy as adjuvant treatment of
      resected non-small cell lung cancer even if results shoud be carefully examined.
      At present, adjuvant chemotherapy in non-small cell cancer should not be reserved
      to experimental trials.

PMID- 15852733
TI  - Neoadjuvant concurrent chemotherapy and radiotherapy in non-small cell lung
      cancer.
AB  - Abstract. Radiotherapy was the standard treatment for patients with locally
      advanced non-small cell lung cancer until the mid 1990s. Chemotherapy was added
      in order to improve outcome, and during the last decade sequential, concurrent or
      mixed modalities have been extensively explored and discussed. Goals of
      neoadjuvant chemoradiation are resecability and downstaging. Recent published
      experiences evidenced that neoadjuvant chemoradiotherapy is feasible if delivered
      with low total dose and limited volume; pathological downstaging to stage 0-I
      could be a reasonable surrogate end-point for overall and disease free survival
      and for distant metastasis.

PMID- 15852734
TI  - Induction therapy before surgery for non-small cell lung cancer.
AB  - Surgery alone is currently still accepted as the principal therapy for cure for
      patients with localized non-small cell lung cancer. The optimal therapy in
      locally advanced and unresectable stage III disease remains unclear. The limited
      performance of each single therapeutic strategy (surgery, radiotherapy, or
      chemotherapy) in the treatment of locally advanced non-small cell lung cancer
      accounted for the rationale of the many attempts at improvement by integrating
      the different approaches. In recent years, to improve clinical outcome,
      chemotherapy or chemoradiation followed by surgery, and definitive chemoradiation
      have commonly been used. Despite numerous phase-II trials, little evidence from
      randomized phase-III trials has been generated. The ongoing randomized trials
      will probably provide more reliable indications to define the management of the
      large number of patients with locally advanced disease.

PMID- 15852735
TI  - Cancer-related fatigue: evaluation and treatment.
AB  - Cancer-related fatigue is one of the most common and disabling conditions
      referred by patients with neoplastic diseases. However, it is one of the symptoms
      related to cancer and its treatment, oncologists largely underestimate. The
      guidelines of the National Comprehensive Cancer Network on the diagnosis and
      treatment of this multifactorial pathology are illustrated. Attention is focused
      on the most recent evidences present in the literature about the therapeutic
      benefit of physical exercise and its effects on muscular function,
      cardiorespiratory performance and life quality of oncologic patients.

PMID- 15852736
TI  - Intraoperative complications in lung cancer surgery.
AB  - Lung cancer surgery is burdened by complications often related to the performed
      procedure. An accidental damage to thoracic structures may be caused by the
      surgeon's incorrect operative management. Elective thoracic surgery for lung
      cancer includes technically well-known operations. However, thoracic anatomy is
      characterized by a number of variants which a thoracic surgeon should know to be
      able to tackle serious situations. In this review the major variants and hazards
      which may be the cause of operative problems are presented. An approach to
      control hiatrogenic damages while performing lung resection for neoplastic
      lesions is suggested. It is stressed that surgical injuries, especially in
      thoracic surgery, should be prevented rather than repaired.

PMID- 15852737
TI  - Intraoperative aspects and complications for the anesthesiologist in the
      management of patients undergoing thoracic surgery for lung cancer.
AB  - Surgery, when feasible, rappresents the treatment of choice for lung cancer.
      Several problems can come to the attention of the anesthesiologist in relation to
      the respiratory function with implications in airway control (double-lumen tube
      for lung collapse required for better surgical exposure of the pulmonary tissue),
      mechanical and gas-exchange aspects (increase in airway pressure of the dependent
      lung, increased blood shunt). The effect of these disorders, with no compensatory
      mechanism (pulmonary hypoxic vasoconstriction) and in the absence of an
      anesthesiologist (higher FiO2, low tidal volumes, allowing "permissive
      hypercapnia", CPAP to the non-dependent lung), normal arterial oxygenation
      (hypoxemia) is impaired. Right heart failure is the major risk particularly in
      preexisting pulmonary hypertension Supraventricular arrytmias can often occur in
      case of history of cardiovascular disease, metabolic and mechanical
      intraoperative alterations (type and duration of surgery, pericardial and
      autonomic nervous system manipulations). Unusual complications are cardiac
      herniation and pulmonary re-expansion-edema.

PMID- 15852738
TI  - Postoperative complications after thoracic surgery for lung cancer.
AB  - Postoperative complications and related risk factors after lung reduction surgery
      are analyzed based on a review of the literature. In particular the pathogenesis
      of some of postoperative respiratory disorders is carefully assessed. Most
      commonly cardiac arrhythmias, respiratory failure, bronchopleural fistula are
      observed. Main risk factors for postoperative complications are old age, chronic
      obstructive pulmonary disease, coronary disease, poor nutritional state,
      neoadjuvant therapy. Attention should be paid to all these factors, both in
      preoperative assessment and postoperative care, to prevent and promptly treat
      postoperative complications.

PMID- 15852739
TI  - [Penalty standards for professional medical responsibility in lung cancer].

PMID- 15852740
TI  - [Medical responsibility in civil law].

PMID- 15852741
TI  - The obesity epidemic--a challenge of this century.

PMID- 15852742
TI  - Variability in lipid profile before and after coronary artery bypass grafting
      (CABG).
AB  - OBJECTIVE: To investigate changes in total cholesterol, low density lipoprotein
      (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, and triglycerides
      in serum of Pakistani patients before, immediately after and 5 days post CABG.
      METHOD: Serum samples from 31 consecutive Pakistani angina patients undergoing
      CABG at the Aga Khan University Hospital were analyzed for total cholesterol, LDL
      cholesterol, HDL cholesterol and triglycerides using kit methods. RESULTS:
      Immediately after CABG, there is a significant decline in the mean levels of
      serum cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. However, 5
      days post CABG, there is a significant increase in the concentrations of total
      cholesterol (P = 0.01) and LDL cholesterol (P = 0.001) in nondiabetic angina
      patients (n = 13). Among the diabetic group of patients (n = 18), the levels of
      total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides went back
      to the pre-operative levels within 5 days post CABG. Compared to European
      patients, Pakistani patients tend to have very low levels of HDL cholesterol
      (24.9 +/- 7.1 mg/dl) and high levels of triglycerides (185 +/- 50 mg/dl) on day 5
      post CABG. CONCLUSION: Since risk of mortality following CABG increases with low
      level of HDL cholesterol and high level of triglycerides, close monitoring and
      treatment of high lipid levels of Pakistani patients following CABG is necessary
      to prevent further coronary events.

PMID- 15852743
TI  - Impact of cyclosporin immunosuppression on serum magnesium and its fractional
      excretion in renal transplant recipients.
AB  - OBJECTIVE: To evaluate the effect of cyclosporine (CSA) on serum magnesium and
      its fractional excretion in renal transplant recipients. METHODS: A cross
      sectional comparative study on 50 live related renal transplant recipients on CSA
      therapy with serum creatinine < 2.0 mg/dl and 30 healthy controls. Serum
      creatinine, magnesium and its fractional excretion and CSA levels were monitored.
      Patients were followed at 6 months. RESULTS: The mean serum creatinine in
      patients was 1.41 +/- 0.42 mg/dl, cyclosporine 210 +/- 66 ng/ml at a dose of 4.8
      +/- 1.4 mg/kg/day. The serum magnesium was 1.77 +/- 0.32 mg/dl vs 1.98 +/- 0.17
      mg/dl in healthy controls (p < 0.05). Fractional excretion was 5.05 +/- 2.53% in
      patients vs 2.8 +/- 1.05% in controls (p < 0.05). No correlation was found
      between CSA levels (100-400 ng/ml) and serum magnesium (r = 0.053) or FEMg% (r =
      0.215). Of the 50 recipients 27 (54%) had FEMg% in the control range. At 6 months
      follow up no difference in CSA levels was found between recipients with FEMg% in
      the normal range vs those with FEMg > 5%. However, serum creatinine increased
      from 1.42 +/- 0.30 mg/dl to 1.68 +/- 0.82 mg/dl (p < 0.05). CONCLUSION: CSA
      therapy lowers serum magnesium as compared to healthy controls and there is
      marked increase in FEMg% in 50% of the patients. Patients with FEMg > 5%
      developed renal function deterioration. FEMg percent can thus be a good follow up
      marker of CSA chronic toxicity in stable transplant recipients.

PMID- 15852744
TI  - Immunophenotypic characterization of high grade pleomorphic sarcomas: a
      demographic and immunohistochemical study in a major referral center of Pakistan.
AB  - OBJECTIVE: Immunophenotypic characterization of high grade (pleomorphic) sarcomas
      and determination of their frequency, mean/median age, sex preferences and common
      sites in Pakistani patients. METHODS: This study included 134 consecutive cases
      of high grade (pleomorphic) sarcomas diagnosed in adults above the age of 15
      years in the section of histopathology at theAga Khan University Hospital,
      Karachi during a period of two years. These high grade (pleomorphic) sarcomas
      were immunophenotyped using a panel including antibodies against Vimentin,
      Desmin, Smooth muscle Actin, S 100, CD34, CD68 and Cytokeratin etc by indirect
      immunoperoxidase. RESULTS: Of the 134 cases which were characterized, 38.1% were
      pleomorphic leiomyosarcoma, followed by pleomorphic rhabdomyosarcoma 14.9%,
      Malignant Peripheral Nerve Sheath Tumour 9%, pleomorphic liposarcoma 3.7% and
      pleomorphic storiform Malignant Fibrous Histiocytoma 0.7%. Thirty three percent
      of cases could not be characterized further. Mean/ median age for Leiomyosarcoma
      was 50/50, for Rhabdomyosarcomas 33/22, for MPNST 42/41, for Liposarcoma 52/50
      and for Malignant Fibrous Histiocytoma 46/46 respectively. The commonest site for
      leiomyosarcoma was lower limb (43%), for rhabdomyosarcoma head and neck (42%),
      for MPNSTthorax (36.4%) and for liposarcoma abdomen (50%). CONCLUSION: It was
      concluded that the most common pleomorphic sarcoma occurring in our adult
      population was Leiomyosarcoma, and that immunohistochemical stains are essential
      in most cases for further characterization of pleomorphic high grade sarcoma.

PMID- 15852745
TI  - The role of thrombofilia related to Factor V Leiden and Factor II G20210A
      mutations in recurrent abortions.
AB  - OBJECTIVE: To study, the impact of thrombophilia caused by Factor V, Factor ll
      G20210A mutations on recurrent abortions, the prevelance of Factor V Leiden and
      Factor II G20210A mutation in patients with habitual abortions. METHODS: Forty
      one patients with a diagnosis of habitual abortion were enrolled in the study.
      Control group consisted of 50 women without a history of poor obstetric outcome.
      10 ml. peripheral venous blood was taken from study and control groups and
      transferred to EDTA tubes, and were tested for Factor V Leiden and Factor II
      G20210A mutations by PCR in genetics laboratory. RESULTS: Phenotypes of 91 cases
      were determined by PCR for Factor V Leiden. It was established that of 41
      patients in the study group, 31 (75.6%) had GG genotype, 9 (22%) had GA genotype
      and 1 (2.4%) had AA genotype. In the control group, 45 (90%) of 50 women had GG
      genotype and 5 (10%) had GA genotype. A allele carrier status was found to be
      24.4% in study group and 10% in the control group. The difference between them
      was not statistically significant (p = 0.06). CONCLUSIONS: The results obtained
      from patients and control group have no difference in Factor V Leiden and Factor
      II G20210A mutations.These results suggest that mutations have no role in
      etiology of 1. and 2. trimester recurrent abortions.

PMID- 15852746
TI  - Percutaneous endoscopic gastrostomy: nine years experience in a tertiary care
      centre in Pakistan.
AB  - OBJECTIVE: To review the experience of percutaneous endoscopic gastrostomy (PEG)
      tube placement and its management in the last nine years, at a tertiary care
      center in Pakistan. METHODS: All patients who underwent percutaneous endoscopic
      gastrostomy from January 1995 to January 2004 at Shifa International Hospital,
      Islamabad, were included in this study. The indications, technique, complications
      and follow up were reviewed. RESULTS: A total of 182 persons underwent this
      procedure. There were 118 (65.0%) males and 64 (35.0%) females. Age ranged from
      55-86 years. One hundred seventy five (96.0%) patients had cerebro-vascular
      accident, five (2.75%) had Parkinson's disease and two (1.25%) malignancy. More
      than 99% procedures were successful and no procedure related mortality was noted.
      Mild PEG site infections were encountered in eighteen (9.8%) patients which were
      manageable with local treatment and oral antibiotics. Four (2.2%) patients had
      severe tube site infection and needed parenteral antibiotics. Tube dislodgement
      took place in five (2.75%) patients and had to be removed and reinserted. Thirty
      days follow up was uneventful with regard to the tube. Longest follow up was 736
      days. CONCLUSION: Percutaneous endoscopic gastrostomy had proved a viable means
      of enteral nutrition in patients with neurological impairment. Complications were
      insignificant. However, patient and care giver's education could be improved for
      more effective tube management, and prevention of PEG insertion site infection.

PMID- 15852747
TI  - Pattern of tobacco consumption among adult women of low socioeconomic community
      Karachi, Pakistan.
AB  - OBJECTIVE: To assess pattern and to determine risk factors associated with
      tobacco consumption in various forms among adult women above 18 years of age in a
      low socioeconomic community of Manora Island, Karachi. METHODS: A cross-sectional
      survey was conducted and 200 adult women above 18 years of age were selected
      using systematic sampling with random start from a community of 5000 people in
      Manora Island, Karachi. There were 400 households in the community. Every 2nd
      household was visited and a woman above 18 years was selected. A semi-structured
      pre-tested questionnaire was administered to respondents by investigators. Data
      on tobacco consumption and other variables such as age, sex, marital status,
      education, employment and stress and anxiety related symptoms were obtained.
      RESULTS: A total of 104 (52%) reported tobacco consumption. Use of huqqa (hubble
      bubble) was more prevalent (79%). Women above 30 years of age, being married and
      living in a joint family were more likely to consume tobacco. Illiterate women as
      compared to women with more than five years of schooling were more likely to
      consume tobacco (OR = 3.16,95% CI = 1.13-7.72). Women having household income
      more than 5000 rupees were more likely to consume tobacco (OR = 2.63,95% CI =
      1.36-5.09) and face more financial difficulties at home (OR = 4.72, 95% CI = 2.45
      9.81). Women consuming tobacco reported anxiety related symptoms more as compared
      to women who did not consume tobacco. CONCLUSION: Our study concluded that in
      this particular study setting, huqqa is the commonest form of tobacco consumption
      among women of low socioeconomic class. They start huqqa usually in childhood and
      after marriage by peer pressure especially in joint families. Women consuming
      tobacco report more psychosomatic symptoms and financial difficulties at home.

PMID- 15852748
TI  - Andragogy [corrected] how adults learn.

PMID- 15852749
TI  - Screening for diseases in family practice.
AB  - The active check-over for disease among apparently healthy people is a
      fundamental aspect of prevention. This is perceivable by screening, which is a
      search of unrecognized disease or condition by means of rapidly applied test,
      examination or other procedures in apparently healthy individuals. This is
      carried out in the hope that earlier diagnosis and subsequent management
      favorably alters the natural history of the disease in a significant proportion
      of those who are identified as 'test-positive'. Family Practitioners have
      privilege to provide comprehensive and holistic health care services including
      preventive, curative and rehabilitative on continuous and long-term basis to all
      members of family irrespective of their age, sex and nature of disease and
      condition. Screening of disease being an important preventive strategy should be
      offered by Family Practitioners to their clients when ever recommended and
      appropriate. However, before screening is initiated, a decision must be made
      whether it is worthwhile, which requires scientific, financial and ethical
      justification. This review summarizes the basic concepts and criteria regarding
      the screening for diseases.

PMID- 15852750
TI  - Obesity: an epidemic of the 21st century.

PMID- 15852751
TI  - Unraveling the function of claustrum.
AB  - Claustrum is a thin sheet of gray matter located between external and extreme
      capsules of lentiform nucleus (basal ganglia). Functions of claustrum are still
      not clear. Positron emission tomography (PET) studies have been helpful in
      measuring the cerebral blood flow responses, as reflection of regional neuronal
      activity to various sensory stimuli. With PET it was seen that claustrum of
      healthy males displayed one of the highest activity with visual sexual stimuli.
      Bilateral activation of claustrum was seen to be involved in motivational
      processed, which direct behavior to a sexual goal.

PMID- 15852752
TI  - Lithium-induced nephrogenic diabetes insipidus.
AB  - We report a case of a 43 year-old female who presented with lithium-induced
      nephrogenic diabetes insipidus. This patient had history of bipolar disorder for
      which she had been taking lithium carbonate for last 16 years. Appropriate work
      up was done and she was diagnosed with nephrogenic diabetes insipidus, secondary
      to lithium toxicity, and was managed accordingly.

PMID- 15852753
TI  - A case of non-resolving cough and weight loss.
AB  - Sarcoidosis is a chronic granulomatous multi-system disease with a clinical
      picture often mimicking tuberculosis. We present a case of a patient who
      presented with a clinical picture akin to both of these granulomatous disorders
      and was started on anti-tuberculous regimen despite the lack of any solid
      evidence pointing towards tuberculosis. As a result her clinical condition
      continued to deteriorate for months until finally a bronchoscopic biopsy
      established her disease process as sarcoidosis. She was then started on systemic
      corticosteroid therapy for sarcoidosis and during the ensuing period has shown
      marked improvement in her clinical picture with near normalization of the
      biochemical and radiographic parameters of her pathology. This case illustrates
      the need for vigilant interpretation of the clinical scenario in patients such as
      these where a misdiagnosis may lead to significant patient distress as well as
      weighing down on the economic and health resources.

PMID- 15852754
TI  - False-positive HIV test.

PMID- 15852755
TI  - Modern technology in lifelong learning of occupational medicine.
AB  - The introduction of new learning technologies and an increasing usage of the
      Internet have the potential of changing the image of postgraduate education. A
      rapid progress in innovative communication systems has lead to essential changes
      in conditions of acquiring knowledge and professional skills. This has resulted
      in the development of different educational models and the incorporation of
      computer-assisted education into training programs. In 2002, the School of Public
      Health at the Nofer Institute of Occupational Medicine has launched first in
      Poland the introductory course in occupational medicine specialization in the
      form of distance education. The course was recognized to be equivalent to the
      traditional face-to-face education. The training process was based on the use of
      CD-ROM. E-mail was used as the main means of communication to facilitate the
      exchange between trainers and trainees. Particularly wide interest in distance
      education among physicians specializing in occupational medicine indicates the
      need to consider the possibility of introducing consecutive courses, which are
      required for specialization or for other professional developments in this form
      of teaching. The purpose of this paper was to discuss the development and
      implementation of a distance learning course taking into consideration the
      academic and educational requirements necessary for effective education and
      training at the post basic level.

PMID- 15852756
TI  - Vagus nerve participates in regulation of the airways: inflammatory response and
      hyperreactivity induced by occupational asthmogens.
AB  - An initial recognition of occupational asthmogens present in dust, fume or
      aerosol particles is carried out by a specialized subset of immune cells,
      dendritic cells and macrophages, present in the airway tissues. When activated by
      asthmogens these cells release proinflammatory molecular signals and not only
      send them to other cells of the innate immunological system, but also activate
      sensory pathways that relay information to the central nervous system (CNS). The
      precise mechanisms by which the peripheral immune system can signal to the CNS
      the airway injury has been the subject of much debate. Recently, a new pathway of
      the CNS-mediated regulation of the peripheral immune response has been found. The
      efferent vagus nerve was proposed as an immune-to-brain pathway and it was
      suggested that acetycholine, the principal vagal neurotransmitter, may directly
      modulate the airway immune response to pathogenic invasion or to injury by
      irritant asthmogens. Sensory innervation of the airways by ascending fibres
      traveling in the vagus nerve as well as by pain sensory pathways, provides an
      important input about the status of injurious challenges in the inflammation zone
      of the airway compartments. These neural inflammation-sensing pathways can
      function at low thresholds of detection and can activate responses even when
      inflammatory agents are present in the airway tissues in quantities that are not
      high enough to reach the brain through the bloodstream. The cholinergic vagus
      nerves participate not only in the regulation of the airways inflammatory
      response. The airways function in response to spastic stimuli such as irritants,
      allergens, and inflammatory mediators is also controlled, in a larger part, by
      efferent vagal endings present in the airway smooth muscles. Cholinergic
      mechanisms represent the predominat constrictor neural pathway in human airways.
      Differences in expression of muscarinic acetylcholine receptors in asthma suggest
      that cholinergic system may participate in the molecular framework influencing
      the airway functions in occupational asthma.

PMID- 15852757
TI  - Occupational allergy to wheat flour. Nasal response to specific inhalative
      challenge in asthma and rhinitis vs. isolated rhinitis: a comparative study.
AB  - OBJECTIVES: The purpose of the study was to compare cytological and biochemical
      changes in nasal lavage fluid induced by wheat flour inhalatory challenge in
      bakers with allergic rhinitis and with asthma accompanied by rhinitis. MATERIALS
      AND METHODS: A single-blind, placebo controlled study was conducted in 64 bakers
      with allergic rhinitis (n = 17), bronchial asthma and rhinitis (n = 24) and
      without occupational allergy (n = 23). Nasal washings were examined before, 30
      min, 4 and 24 h after the specific provocation, wheras non-specific bronchial
      hyperreactivity (PC20) before and after 24 h. RESULTS: A significant decrease in
      PC20 after the challenge test was observed only in patients with asthma and
      rhinitis. Eosinophil count and percentage, basophil count and the permeability
      index induced by specific provocation were significantly increased in both
      rhinitis patients and asthmatics. Moreover, the increase especially in total
      count and proportion of eosinophils as well as in the permeability index was more
      pronounced in subjects suffering from asthma and rhinitis than in those with
      rhinitis alone, although the changes were not statistically significant.
      CONCLUSIONS: The results indicate the applicability of the "nasal pool" technique
      as a simple diagnostic procedure in flour-induced airway allergy. However, the
      evaluation of nasal lavage fluid, although a very sensitive and specific method
      of diagnosing respiratory allergic disease, cannot be used to distinguish
      patients with upper and lower airway allergy.

PMID- 15852758
TI  - Respiratory complaints and medication use following cessation of exposure to
      construction dust and diesel truck emissions (Neve Yakov, Jerusalem).
AB  - OBJECTIVES: The aim of the study was to assess respiratory complaints in the
      residents of Neve Yakov following the closure of a municipal dump, operating in
      the neighborhood for 3 years. MATERIALS AND METHODS: We carried out a cross
      sectional survey of 250 adult residents. Exposures to sporadic dust, measurements
      and estimates of diesel emissions based on traffic load were assessed. RESULTS:
      Adjusted odds ratios for respiratory symptoms in persons living in the nearest
      and downwind areas compared to the areas farthest from the dump site were
      (nearest and downwind respectively): cough OR = 3.7 (95% CI: 1.18-11.4) and OR =
      2.9 (95% CI 0.79-10.9); phlegm OR = 1.9 (0.7-5.1) and OR = 2.3 (0.7-7.3);
      shortness of breath OR = 1.7 (0.6-4.8) and OR = 3.7 (0.9-14.6). After closing the
      dump, 33% of residents reported improvement in symptoms. Following closure of the
      dump, residual respiratory illness was observed in many residents. CONCLUSION: A
      substantial part of the respiratory complaints may have come from diesel
      emissions in addition to the ambient dust.

PMID- 15852759
TI  - Effects of duration of exposure to wood dust on peak expiratory flow rate among
      workers in small scale wood industries.
AB  - OBJECTIVES: Occupational and environmental lung diseases are one of major
      problems of clinical medicine. Several occupations are associated with adverse
      health effects, and the lung is one of the parts of the body most vulnerable to
      airborne hazards. Exposure to gas, fume, and dust can lead to occupational lung
      diseases. The objective of the study was to assess the effects of wood dust and
      the duration of exposure on peak expiratory flow rate (PEFR) and additionally, to
      minimize possible health risks for wood workers by providing them with
      information about wood dust related hazards. METHODS: The present study was
      conducted under the supervision of the Department of Physiology, College of
      Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia during the year
      2002. It was designed as a matched case-control cross-sectional study of
      spirometry in forty six non-smoking wood workers, aged 20-60 years, who worked
      without the benefit of wood dust control ventilation or respiratory protective
      devices. PEFR measurements were performed using an electronic spirometer.
      RESULTS: The present study results demonstrated that in wood workers exposed for
      longer periods than 8 years, PEFR was significantly reduced as compared with
      their matched controls. CONCLUSION: Based on the results of the present study, we
      conclude that PEFR in wood workers is impaired and the stratification of results
      shows a dose-response effect of years of wood dust exposure on its value.

PMID- 15852760
TI  - Leisure-time physical activity, cardiorespiratory fitness and work ability: a
      study in randomly selected residents of Lodz.
AB  - OBJECTIVES: Low physical activity is a serious health problem in developed and
      developing countries. Much attention is also given to the role of physical
      activity in the modification of work ability in adults. The aim of this studywas
      to assess leisure-time physical activity, cardiorespiratory fitness and their
      influence on the subjective work ability in a randomly selected group of
      professionally active residents of Lodz. MATERIALS AND METHODS: The study was
      performed in the randomly selected group of professionally active persons (n =
      198). Physical activity was determined by means of the Seven Day Physical
      Activity Recall (SDPAR). To determine cardiorespiratory fitness in the examined
      persons, the submaximal treadmill test was performed. Subjective work ability was
      evaluated using the work ability index (WAI). RESULTS: Correlation coefficient
      for the WAI and leisure-time physical activity was high r = 0.3, p < 0.0001.
      Moreover, WAI, its compounds and cardiorespiratory fitness were highly correlated
      r = 0.4, p < 0.0001. CONCLUSIONS: Our analysis of leisure-time physical activity,
      cardiorespiratory fitness and WAI emphasizes a great, potential feasibility of
      improving the WAI and its components, e.g., through the development, promotion,
      and broad use of training schedules.

PMID- 15852761
TI  - Industrial differences in disability retirement rates in Denmark, 1996-2000.
AB  - OBJECTIVES: The objective of the study was to identify industries associated with
      a high risk of disability retirement and to roughly estimate the fraction of the
      retirements that can be attributed to a non-optimum work environment. MATERIALS
      AND METHODS: All economically active people in Denmark, aged 20-54 years, in the
      beginning of 1996 (1196235 men and 1063058 women) were followed-up from 1996 to
      2000. Gender stratified and age standardized incidence ratios (SIR) for
      disability retirement were calculated for each of 58 baseline industries. A Monte
      Carlo simulation model was used to estimate attributable fractions. RESULTS: In
      total, we observed 17242 disability retirements among the men and 20910 among the
      women. The attributable fraction was 38% for the women and 40% for the men.
      Twenty-six of the SIR-values (13 among the men and 13 among the women) were
      statistically significantly high. Twenty-two of the 26 groups with a high SIR had
      been identified by previous research as groups at high risk of circulatory
      disease and/or musculoskeletal disorders. Two of the remaining four groups with a
      high SIR were associated with hard physical work (men and women engaged in
      horticulture and forestry) while the other two consisted of men in female
      dominated industries (child-care and cleaning). CONCLUSIONS: The present study
      identified a series of high-risk industries. It also corroborated previous
      findings, which state that circulatory disease and musculoskeletal disorders are
      major risk factors and that hard physical work is an independent risk factor of
      disability retirement. Further research is needed to find out why men in some
      stereotypically feminine industries are at high risk of disability retirement.

PMID- 15852762
TI  - Trends in laryngeal cancer incidence in Lithuania: a future perspective.
AB  - OBJECTIVES: The aim of the present study was to assess the incidence of larynx
      cancer in Lithuania in the years 1978-2001 and to outline possible future trends.
      MATERIALS AND METHODS: The number of new laryngeal cancer cases in 1978-2001 was
      obtained from the Lithuanian Cancer Registry. The Lithuanian Department of
      Statistics provided data on the population being at the same age in the same
      years. The data were adjusted for age, using the direct method in accordance with
      the European standard; a linear regression analysis of trends in the larynx
      cancer incidence was performed. RESULTS: After standardization of data for the
      period of 1978-2001, an upward trend was registered for both men and women: in
      1978 the incidence was 10.73 for men and 0.26 for women per 100000 population, in
      2001 the corresponding data were 11.6 and 0.7. Throughout the study period the
      incidence was higher in men than in women and the mean age of male and female
      larynx cancer patients was increasing: mean age for men was annually increasing
      by 0.1566 years and for women by 0.0602 years. The forecast for men in 2006 is
      13.88 and for women 0.54 cases per 100000 population. CONCLUSIONS: The increase
      in larynx cancer incidence is growing more rapidly among women than among men,
      and the mean age of the patients is also increasing. The forecast is that in 2006
      the incidence rate will be increasing, and both men and women will get ill at an
      older age.

PMID- 15852764
TI  - Different lists of occupational diseases in European Union Member States: is it a
      problem for the law harmonization?

PMID- 15852763
TI  - Serum vasoactive agents in rats poisoned with cadmium.
AB  - OBJECTIVES: Mechanisms of the vascular effect of cadmium vary and involve
      nervous, hormone and intracellular signaling pathways. However, it is still not
      clear if mechanisms of the vascular effect of cadmium (Cd) include changes in the
      synthesis or release of vasoactive agents. The aim of this study was to evaluate
      the impact of subchronic Cd poisoning on blood nitric oxide or endothelin in
      blood and to relate it to the redox system activity in vessel walls and to blood
      Cd concentration. MATERIALS AND METHODS: The study was performed on male Buffalo
      rats which were given cadmium in drinking water, 50 or 200 ppm, for 12 weeks.
      RESULTS: The study showed different dose-dependent changes in toxicological and
      biochemical status. Mean serum nitric oxide concentration (measured using R&D
      Systems) was lower in rats poisoned with cadmium compared with the control group
      (57.7 +/- 7.6 vs. control 65.0 +/- 4.9 micromol/l, p < 0.05), whereas the plasma
      endothelin-1 level (measured using enzymoimmunoassay) and serum prostaglandin
      PGF2alpha concentration (determined using R&D System) were similar in all
      animals. The lipid peroxides concentration (measured colorimetrically) was higher
      in the group treated with cadmium in a dose of 50 ppm than in controls (5.2 +/-
      3.0 vs. controls 1.4 +/- 0.4 nmol/ml, p < 0.001) and gluthatione concentration
      was decreased in the group treated with cadmium in a dose of 200 ppm as compared
      with the control group, (1.3 +/- 1.2 vs. control 2.5 +/- 0.9, micromol/l p <
      0.05). CONCLUSIONS: It is concluded, that cadmium induces oxidative stress in
      both doses, however, the activity of defending mechanisms depends on Cd dose.
      Oxidative stress can be responsible for decreased nitric oxide concentration in
      serum. We suppose that the mechanisms of the vascular effect of cadmium vary and
      are dose-dependent. Cd used in a dose of 50 ppm for three months induces more
      severe functional vascular disturbances than its dose of 200 ppm.

PMID- 15852765
TI  - Polish bibliography of occupational medicine, 2003.

PMID- 15852766
TI  - Getting tougher. Punishments by state medical boards up nearly 20%.

PMID- 15852767
TI  - Women even the odds. Healthcare isn't an "old boys' network" anymore, as women
      catch up to men in leadership positions.
AB  - Women are increasingly taking influential jobs in healthcare, whether it's
      Carolyn Clancy at the AHRQ helping lead the way on improving quality through IT
      or Risa Lavizzo-Mourey helping dole out millions of dollars in grants at the
      Robert Wood Johnson Foundation. Both won spots on Modern Healthcare's inaugural
      list of the Top 25 Women in Healthcare.

PMID- 15852768
TI  - Coming soon. HIPAA compliance deadline looms for security.

PMID- 15852769
TI  - Intergovernmental gimmicks. Hospitals caught in the middle of finger-pointing.

PMID- 15852770
TI  - Try, try again. Mease, Morton Plant to pursue another merger.

PMID- 15852771
TI  - System upgrade. Not-for-profits have a good first quarter.

PMID- 15852772
TI  - Miami system suffers big loss.

PMID- 15852773
TI  - Scrushy wins a round. 'Perjury trap' ruling could affect other cases.

PMID- 15852774
TI  - One of their own. Doc-execs' toughest challenges come from the inside.

PMID- 15852775
TI  - Building consolidation. Costs not expected to rise for providers.

PMID- 15852776
TI  - Senior-living market grows.

PMID- 15852777
TI  - It's women's turn. Top 25 female health execs point the way to change in male
      dominated industry.

PMID- 15852778
TI  - Rx for e-prescribing. Groups offer comments on proposed standards.

PMID- 15852779
TI  - [Genetic determination of smell].
AB  - The recent study of olfactory receptor genes sheds new light on the significance
      of this receptor not only for smell recognition but also in human embryogenesis.
      In this work current data concerning the role of olfactory receptors in human as
      well as their genetic determination are presented. Olfactory receptors are
      encoding approximately by 1000 hOR genes. The hOR gene family is most likely the
      largest in human genome. Among 1000 hOR genes, 347 are functional, the rest 70%
      being pseudogenes are not expressed. HOR genes reside at 25 locations in human
      genome in multiple clusters on all human chromosomes, except 2, 4, 18, 20, 21,
      and Y. Each receptor recognizes single as well as multiple odorant, and each
      odorant binds to multiple receptors to generate specific activation patterns for
      each of a great number of distinct smells. There is more and more evidence
      showing close correlation between HLA complex and smell recognition, which
      influence mating behavior in animals, consequently leading to increase immune
      response to various pathogens. The last investigations showed hOR expression in
      germinal cells and in developing embryo, suggest that hOR may play functional
      role in cell recognition in organogenesis.

PMID- 15852780
TI  - [The Erbium-Yag laser in stapes surgery].
AB  - Laser has been used for 21 years in otology. This technique was introduced to
      decrease the number of complications after micromanipulations within the middle
      ear. Continuous-wave laser and pulsed laser have clinical application. In the ENT
      Dept. in Poznan pulsed Er-Yag laser (Zeiss Corp.) is used in the treatment of
      otosclerosis. First experiences and results of treatment of 35 patients using
      this method were presented. In all patients recovery of hearing was observed. No
      damage of the inner ear (deafness or hypoacusis) was found.

PMID- 15852781
TI  - [Manometric analysis of the oral and pharyngeal phases of the act of swallowing].
AB  - Manometric analysis of swallowing was conducted on 35 subjects, aged 44 to 60.
      The course of physiological changes in pressure during oral and pharyngeal phase
      of swallowing was analysed. To objectify the evaluation of analysed phenomena,
      parameters that include both pressure values inside pharynx and oesophagus and
      time dependences connected with changes in their value were used as proposed by
      the authors of this paper and as applied by other authors involved with these
      issues.

PMID- 15852782
TI  - [Complications of three methods of stapedectomy].
AB  - In a group of 270 partial stapedectomies performed by one surgeon using teflon
      piston prosthesis it was assessed whether incidence of complications depended on
      sequence of surgical steps. In group I of 50 ears classical stapedectomy was
      performed: 1. removal of stapes superstructure, 2. making a hole in the
      footplate, 3. placing the prosthesis on the incus. In group II of 167 ears the
      hole in the footplate was made before removal of stapes arch. In group III of 53
      ears: 1. the hole in the footplate, 2. placing the prosthesis on the incus, 3.
      removal of stapes arch, was performed. Total deafness had one patient of the
      whole group. No patient had perilymphatic fistula and facial nerve palsy.
      Floating footplate developed in 4 patients of group I, in one patient of group II
      and in none patient of group III. Subluxation of incus developed in 3 patients of
      group I, in 12 patients of group II and in none patient of group III. Comparison
      of three stapedectomy methods showed that making the hole in the footplate before
      removal of stapes arch prevents floating footplate and placing the prosthesis on
      the incus before removal of stapes arch prevents subluxation of the incus.

PMID- 15852783
TI  - [Clinical and immunohistoenzymatic investigations in patients with vasomotor and
      perennial allergic rhinitis].
AB  - The aim of our study was evaluation of the results of clinical examination in
      patients with vasomotor and perennial allergic rhinitis and assessment of number
      of blood vessels, nerve fibres and mast cells on the basis of
      immunohistoenzymatic examination. There were 42 patients examined aged from 18 to
      50 and divided into three groups: I--16 patients with vasomotor rhinitis and II-
      14 patients with perennial allergic rhinitis and III--12 patients (control) with
      nasal septum deviation. On the basis of the patient's history data, clinical
      otorhinolaryngologic examination and active anterior rhinomanometry the patients
      were qualified to bilateral inferior turbinectomy. The nasal mucosa removed
      during surgery underwent immunohistoenzymatic examination using the monoclonal
      antibody against the tryptase of mast cells (MCT company, DAKO), the endothelin
      of blood vessels (EC - DAKO) and the neurospecific enolase (NSE - DAKO). In
      examined groups of patients with vasomotor and perennial allergic rhinitis and
      control group similar escalation of clinical symptoms expressed by means of
      points index were stated. In immunohistoenzymatic studies the differences in mean
      number of blood vessels and nerve fibres between examined groups were not
      statistically significant, however statistically significant difference concerned
      higher number of mast cells patients with vasomotor rhinitis in comparison to
      perennial allergic rhinitis.

PMID- 15852784
TI  - [Problems in swallowing after partial supraglottic and supracricoid
      laryngectomy].
AB  - The results of above 30 year research of pharyngeal phase of deglutition act in
      patients after classical and extended supraglottic laryngectomies and
      supracricoid laryngectomies are presented and compared with physiologic data.
      Initially roentgenocinematographic method has been used, computerized topokinetic
      analysis of acquired images was introduced later. With the latter method
      visualization of the deglutition act was better and the analysis more objective.
      The main purpose of the study was to find which functions and structures were
      spared after operations, that were necessary to facilitate pharyngeal phase of
      deglutition act and make it similar to physiologic act of deglutition.

PMID- 15852785
TI  - [Treatment of labyrinthine fistulas in chronic otitis media].
AB  - Labyrinthine fistulas (l.f.) are reported to be diagnosed in 3-12.9% of the
      chronic otitis media patients. Their most frequent location is the lateral
      semicircular canal. The other locations include posterior semicircular canal,
      superior s.c. and vestibular window. Surgical removal of the cholesteatoma matrix
      brings a high risk of the complete hearing loss in the operated ear. Preoperative
      diagnosis of the l.f. is not always possible. Authors present the analysis of the
      group of 18 patients with l.f. treated at the Otosurgery Department, Medical
      University of Lodz. In all patients the radical modified surgery has been
      performed. Postoperative results are strictly correlated to the l.f location and
      size. As a conclusion authors present an algorithm of the l.f. surgical treatment
      based on their experience.

PMID- 15852786
TI  - [Use of intratympanic gentamycin for the treatment of Meniere's disease].
AB  - The ablation treatment of Meniere's disease by intratympanic streptomycin
      applications was first reported by Schuknecht in 1957. Streptomycin and
      gentamycin are the most frequent aminoglycosides used for the Meniere's disease
      treatment. Gentamycin is responsible for the damage of vestibular dark cells
      causing the impairment of endolymph production. This method gives the possibility
      for the control of the vertigo with a potential hearing preservation. Fifteen
      patients with unilateral Meniere's disease who had not responded to conventional
      therapy, were treated by intratympanic gentamycin injections. The hearing status
      and the caloric test were staged before and after treatment according to the AAO
      HNS guidelines. Overall results after minimum 1 year follow-up in this group were
      as shown below: complete vertigo control--5 patients, substantial vertigo control
      -8 patients, complete relief of tinnitus--10, relief of aural fullness--12
      patients, hearing loss--none. According to presented results, intratympanic
      injections of gentamycin is the useful alternative to the surgery. This method
      should be consider in every patient with the unilateral Meniere's disease, who
      had not responded to the conventional treatment.

PMID- 15852787
TI  - [Usefulness of questionnaire EORTC QLQ C-30 and EORTC QLQ H&N C-35 in assessment
      of quality of life before surgical treatment in patients with head and neck
      cancer].
AB  - BACKGROUND: Quality of life (Qob) has become an important issue in head and neck
      cancer. Nowadays the explanation of factors predicting quality of life after
      surgical treatment has important role and implications for patient's management.
      METHODS: We analyzed which pretreatment parameters and factors predicted QoL
      after surgery of 46 patients with larynx cancer. The patients completed the EORTC
      Core Questionnaire, the Head and Neck Module. RESULTS: The QLQ H&N35 Core
      Questionnaire demonstrated acceptable reliability. The instrument was sensitive
      to the effect of patients' disagreement of quality of life state. Scores were
      significant associated with total quality of life score. CONCLUSIONS: Results
      support the sensitivity and applicability of Core Questionnaire. The use of this
      disease-specific measure to assess quality of life among patients with advanced
      larynx cancer.

PMID- 15852789
TI  - [Tumor escaping mechanisms present in microenvironment of laryngeal cancer].
AB  - In tumor tissue obtained from a group of 21 patients treated surgically for
      laryngeal carcinoma, the expression of Fas, Fas-L, CD3, TCR zeta chain and Bcl-2
      were estimated. It has been shown that tumor often express: Fas-L, Fas, Bcl-2,
      the molecules which may influence increased tumor survival. On the other hand
      lack of MHC class I antigen expression on tumor cells frequently has been
      observed. As it is known, such tumor cells can not be recognized by cytotoxic T
      lymphocytes. Frequently observed decreased expression of TCR zeta chain and high
      level of apoptosis among T cells present in tumor microenvironment seems to
      depend on direct interactions with molecules expressed by tumor. Understanding of
      these interactions may be of great importance in evaluation of tumor
      aggressiveness, patients follow up and the approach to treatment.

PMID- 15852788
TI  - [Role of sentinel lymph nodes in treatment of head and neck cancer].
AB  - Current points of view on significance of sentinel node biopsy in No-neck are
      presented and at the same time is pointed out the importance of this technique
      for the detection of occult cervical metastases. Methods of identification of the
      sentinel lymph nodes are described. Usefulness of the handheld gamma probe to
      determine the position of sentinel nodes during operative procedure was
      emphasised.

PMID- 15852790
TI  - [Bone anchored hearing aids (BAHA) used for treatment of conductive hypoacusis-
      current problems in Poland].
AB  - Basic principles, indications and limitations of BAHA implantation as well as
      different kinds of operation techniques are presented. The beginning and the
      development of BAHA use in Poland are mentioned together with some difficulties
      in broadening of this kind of implantation.

PMID- 15852791
TI  - [Rare case of multiple primary malignant neoplasm of the larynx: squamous
      carcinoma and fibrosarcoma].
AB  - The problem of primary mixed neoplasms has been recently a subject of numerous
      research works trying to find out their pathogenetic mechanisms, early detection,
      clinical course and treatment opportunities. The authors present a rare case
      (fibrosarcoma and squamous carcinoma) in a 73-year-old man. The patient had a
      surgery (total laryngectomy) and complementary irradiation at the Institute of
      Oncology.

PMID- 15852792
TI  - [Hypopharyngeal carcinoma in 24 years old female].
AB  - A case of multifocal squamous cell carcinoma of posterior wall of the hypopharynx
      in 24 year female was described. A course of the disease and treatment were
      presented. Despite radical combined therapy patient died 1,5 year after the tumor
      diagnosis.

PMID- 15852793
TI  - [Double adenoid cystic and squamous cells carcinoma of the hypopharynx and
      larynx. A contribution to the issue of multicomponent neoplasms].
AB  - Bicomponent cancer of the piriform fossa and larynx of 55 years old man has been
      described. The patient was treated surgically and by radiotherapy. The
      performance of laryngectomy and partial pharyngectomy with conservative bilateral
      neck dissection was used as surgical treatment. In histopathological findings of
      postoperative specimens two types of neoplasms: squamous cells and adenoid-cystic
      cancers were stated. The authors presented opinions on the affection arising of
      multicomponent tumours of the aerodigestive truct.

PMID- 15852794
TI  - [Myoepitheliomas of the palate].
AB  - The authors present a case of myoepithelioma of the palate. Frequency, treatment
      and pathologic diagnosis of the disease are discussed. A Polish name of the
      disease is suggested.

PMID- 15852795
TI  - [Diseases of the larynx and voice disorders in teachers after many years of
      performing their profession, claiming the recognition of occupational disease].

PMID- 15852796
TI  - Healthcare professionals to operate!

PMID- 15852797
TI  - Relevant healthcare education.

PMID- 15852798
TI  - NHS IT costs out of control?

PMID- 15852799
TI  - It's nice to be nice.

PMID- 15852800
TI  - Shaping my own future.

PMID- 15852801
TI  - Achieving your potential!
AB  - Many of us peruse job advertisements, in Job Forum, the nursing press and
      relevant newspapers as well as searching the web. Some are looking for a change
      of employment, but perhaps most of us are just curious as to what is on offer
      around the country. At some point, it is likely you will see a job that you want
      and know that you are capable of doing it well, and you will need to maximise
      your chances of being successful. This article aims to assist you in getting the
      job you want by providing information on the job application and interview
      processes.

PMID- 15852802
TI  - Applying cricoid pressure.
AB  - This article discusses the literature surrounding the application of cricoid
      pressure during rapid sequence induction and suggests ways in which the training
      of this skill can be improved.

PMID- 15852803
TI  - Daisy Ayris Lecture. The operating room: a personal history.
AB  - This is the first of two articles based on a presentation given at NATN Congress
      2004. The presentation was given as the Daisy Ayris Memorial Lecture. In this
      article NATN archivist Nancy Cox describes her experiences working in the
      operating room beginning in the 1950s.

PMID- 15852804
TI  - A surgical care practitioners' pilot programme in Wales.
AB  - The Surgical Care Practitioner Pilot Programme, funded by the Welsh Assembly
      Government, commenced in October 2003. Preliminary evidence suggests that the
      pilot is making a significant difference to the care of surgical patients in
      those NHS trusts involved. The authors describe why the programme was initiated
      and what it was designed to deliver, together with the preliminary evaluation.

PMID- 15852805
TI  - [The synthesis and characteristic of Co3O4 nanocrystals].
AB  - The authors found a new method to synthesize Co3O4 nanocrystals, which were
      synthesized using Co(CH3COO)2 x4H2O and PVP as precursor. The as-prepared
      products were measured by SEM, TEM and XRD. Co(CH3COO)2 x 4H2O and PVP were
      dissolved together in a kind of solvent. Then, the solution was vaporized in
      water bath at 60 degrees C till the solution became viscid. The viscid solution
      was transferred into a ceramic boat and was dried in a oven at 110 degrees C for
      12 hours. Finally, the dried sample was calcined in tube-like stove at 400
      degrees C for 2 hours in air to produce the Co3O4 nanocrystals. To prepare the
      precursor composed of PVP and Co (CH3COO)2 x 4H2O, the authors employed two
      different solvent (ethanol and H2O). It was found that different appearance of
      Co3O4 nanocrystals was achieved by using different solvent. When ethanol is used
      as solvent, the prepared spherical particles with diameter of about 1 microm were
      consisted of Co3O4 nanocrystals with diameter of 20-50 nm. However, only Co3O4
      nanocrystals with diameter of 20 nm were synthesized when H2O is used as solvent.
      This indicated that the solvent played a big role for the final appearance of
      Co3O4 nanocrystals.

PMID- 15852806
TI  - [Studies on fluorescent properties of multi-walled carbon nanotubes before and
      after concentrated nitric acid treatment].
AB  - Fluorescent properties of multi-walled carbon nanotubes (MWNTs) before and after
      concentrated nitric acid treatment were studied. The results show that both multi
      walled carbon nanotubes (MWNTs) and treated multi-walled carbon nanotubes (t
      MWNTs) could emit fluorescence; compared with MWNTs, fluorescence from t-MWNTs is
      stronger and fluorescent emission peak from t-MWNTs blue shifts slightly to short
      wavelength. Luminescence from MWNTs could be related to the trapping of
      excitation energy at defect sites and the energy bandgap between the lowest
      unoccupied molecular orbital (LUMO) and the highest occupied molecular orbital
      (HOMO). Treating MWNTs with concentrated nitric acid could introduce more defects
      on MWNTs and make MWTNs trap more excitation energy, leading to a fluorescence
      enhancement of t-MWTNs; in addition, the energy bandgap between LUMO and HOMO
      increases with length decreasing of MWNT, and the shortening of MWNT caused by
      concentrated nitric acid treatment could make energy bandgap between LUMO and
      HOMO increase, resulting in a slight blue shift of fluorescent emission peak of t
      MWTNs to short wavelength.

PMID- 15852807
TI  - [Up-conversion luminescence and volumetric display research on Er(0.5): FOG
      material excited by 1 520 nm laser].
AB  - The volumetric display technology is one of the important science frontiers of
      modern society. Multi-photon up-conversion volumetric 3-D display, attractive
      especially in its self-spatial vision, has the advantages of total
      solidification, high reliability and speedy operation so that it has a broad
      range of applications. The up-conversion luminescence of oxyfluoride glass
      material Er(0.5): FOG, when excited by 1 520 nm semiconductor laser, was studied.
      The common-fluorescence spectra were measured also, in order to know up
      conversion sufficiently. It was found that there are several up-conversion
      luminescence lines (407.43, 411.20 nm), (522.51(m), 528.57 nm), (540.53(m),
      543.70, 549.00 nm), (654.75(m), 665.50 nm) and 802.10(m) nm, which can be
      recognized as the fluorescence-transitions of (2G4F2H)9/2 --> 4 I15/2, 4H11/2 -->
      4 I15/2, 4S3/2 --> 4 I15/2, 4F9/2 --> 4I15/2 and 4I9/2 --> I15/2 respectively. It
      is interesting that the slopes of log F-log P curves, the double logarithmic
      variation of up-conversion luminescence intensity F with the laser power P, are
      various for these observed up-conversion luminescences, which are valuable for
      volumetric display. The comprehensive analysis found that the (2G4F2H)9/2 -->
      4I15/2 up-conversion luminescence is a four photon up-conversion luminescence,
      while [2 H11/2 --> 4I15/2, 4S3/2 --> 4I15/2 and 4F9/2 --> 4I15/2] up-conversion
      luminescence is three-photon up-conversion luminescences, and 4I9/2 --> 4I15/2 up
      conversion luminescence is a two-photon up-conversion luminescence. It was found
      also that the absorption from the ground-state 4I15/2 level to first excited
      level is very large, resulting in the fact that the sequential energy transfer
      and step-by-step absorption up-conversion are readily to happen.

PMID- 15852808
TI  - [Luminescence of Eu3+ ions in nanocrystalline zirconia].
AB  - Zirconia doped with 1 mol% Eu3+ and annealed at 600, 800 and 1 000 degrees C and
      zirconia doped with 1 mol%, 3 mol%, 5 mol% Eu3+ and annealed at 800 degrees C
      were prepared by co-precipitation method; luminescence of Eu3+ ions was
      investigated under 394 nm excitation, and the emission of 5D0 -->7F2 was peaked
      at 604 nm in zirconia annealed at 600 and 800 degrees C, however, peaked at 610
      nm in the sample annealed at 1 000 degrees C. By studying omega2 of 5 D0 --> 7F2,
      the authors found that omega2 increased with increasing annealing temperature.
      When monitored with 604 nm, the authors found that the contribution of population
      of 5L6 level to the luminescence of 5D0 --> 7F2 increased with increasing
      annealing temperature. By investigating the luminescence in the samples doped
      with 1 mol%, 3 mol% and 5 mol% Eu3+ ions, we found that the emission of 5D0 -->
      7F1 transition for the sample doped with 3 mol% Eu3+ ions was a broad band peaked
      at 597 nm.

PMID- 15852809
TI  - [Photovoltaic character of organic EL devices MEH-PPV/Alq3].
AB  - An organic photovoltaic(PV) cell, ITO/MEH-PPV/Alq3/LiF/Al, was fabricated. The
      MEH-PPV and Alq3 are the electron-acceptor and donor in the cell, respectively.
      The respond region matchs the adsorption of Alq3 film. Under UV light with 0.5 mW
      x cm(-2), the cell shows a short-circuit current of 2.4 microA x cm(-2), open
      circuit voltage of 2.6 V, a fill factor of 0.71, and a power conversion
      efficiency of 0.9%. It was found that the PV cell indicates electroluminescence
      (EL) performance and could emit orange light at DC voltage. The maximum luminance
      is about 1 000 cd x cm(-2) at 15 V.

PMID- 15852810
TI  - [Photoelectron decay time-resolved spectrum of AgCl crystals doped with K4Ru(CN)6
      complex].
AB  - Microwave absorption and film dielectric spectrum detection technology was used
      to study the influence of complex K4Ru (CN)6 on the photoelectron decay time
      resolved spectrum of cubic AgCl crystals illuminated in this paper. The results
      indicate that the influence of the doping content and doping position of the
      complex K4Ru(CN)6 on the photoelectron decay time-resolved spectrum is evident.
      The photoelectron decay process of this emulsion is slowest, and the
      photoelectron lifetime is longest when doped with K4Ru (CN)6 of 2.45 x 10(-5) mol
      x (mol Ag)(-1) at doping positions of 75% Ag.

PMID- 15852811
TI  - [Infrared spectra of polyoxometalates].
AB  - The infrared spectra of polyoxometalates are addressed. The vibration frequencies
      of some synthesized polyoxometalates in recent years are emphasized. It was found
      that the infrared spectra of polyoxometalates result from stretch vibration
      frequency of the metal-oxygen, and 1 100-400 cm(-1) is the region of the
      characteristic absorption peak. The infrared spectrum contains information about
      the symmetry of polyoxoanion as well. As an analytical means, the infrared
      spectrum can be used to distinguish heteropolyanion and provide information on
      structure.

PMID- 15852812
TI  - [Study on application of Fourier transformation near-infrared spectroscopy
      analysis with support vector machine (SVM)].
AB  - Support Vector Machine (SVM) is a method for the research on identifying two
      types of problem. It is the latest branch in the statistics study theories, and
      the identification model has a strict mathematics foundation. In this paper, the
      basic principle and method of SVM are not only introduced, but also applied to
      chemometrics. One hundred and three rhubarb samples were used as experimental
      materials. The identification models were established with near-infrared
      spectroscopy and SVM training method with the intention of identifying whether
      the rhubarb samples are true or false. The thirty-three samples in training set
      were identified by the identifying models with the accurate rate of 100%, while
      seventy estimate samples had an accurate rate of 96.77%. The research result
      provided the method of identifying the traditional Chinese medicine rhubarb
      quickly. So, it shows the feasibility of establishing the models with near
      infrared spectroscopy and SVM method to identify biological samples. This paper
      introduced the theme of SVM training method in order to beget the attention of
      the research members who deal with chemometrics.

PMID- 15852813
TI  - [Quality control of Corydalis Yanhusuo W. T. Wang by second derivative FTIR
      spectroscopy combined with statistics].
AB  - A new method using single reflection Fourier transform infrared spectroscopy was
      proposed for direct and fast determination of Corydalis yanhusuo W. T. Wang of
      traditional Chinese herbal medicines and its confusable varieties. Data were
      collected directly for Fourier transform infrared spectra with OMNI sampler. Then
      through converting FTIR spectra of the samples into second derivative spectra by
      derivative spectra software, it is possible to identify Corydalis yanhusuo W. T.
      Wang from the confusable varieties with statistics. The result shows that the
      second derivative FTIR of Corydalis yanhusuo W. T. Wang and its confusable
      varieties are different in the 2 050-650 cm(-1) range. The probability is less
      than 0.01 and the result is significant. Corydalis yanhnsuo W. T. Wang and its
      confusable varieties can be identified by identifying the inner layer parts of
      the cuticles of samples by second derivative FTIR spectroscopy with statistics
      directly, rapidly and accurately.

PMID- 15852814
TI  - [Raman spectra and photoluminescence spectra of InGaN/GaN multiquantum wells
      annealed].
AB  - InGaN/GaN multiquantum well, grown by MOCVD on a sapphire substrate and annealed
      under the conditions of 700 and 900 degrees C x (20 min)(-1), was studied by
      means of mirco-Raman spectroscopy and photoluminescence. The Raman peak of E2, A1
      showed red shift after multiquantum were wells annealed, and the HWHM of Raman
      peakdecreased imperceptibly. Moreover,the photoluminescence peak of the sample
      annealed under the condition of 700 degrees x (20 min)(-1) showed a red shift,
      then appeared a blue shift under the condition of 900 degrees C x (20 min)(-1).
      These results clearly showed that the sample annealed induced strain stress
      relief that could explain Raman peak shift, but the piezoelectric field induced
      the quantum-confined Stark effect, which can't agree with the photoluminescence
      experiment. Sample annealed could change the width of quantum well and InGa phase
      segregated; these factors influencing structure of quantum well could explain the
      results of photoluminescence spectra.

PMID- 15852815
TI  - [Raman spectra study on the GeS2-Ga2S3-KCl system glasses].
AB  - Raman spectra of GeS2 -Ga2S3-KCl pseudo-ternary system glasses at room
      temperature in the air were probed systematically in the region of 150-500 cm(
      1). Based on the results of Raman spectra and preparing procedure in pseudo
      binary systems GeS2 -KCl and Ga2S3 -KCl, the sole interaction of Ga2S3 and KCl
      was identified and new units GaS3/2 Cl were produced in GeS2 -Ga2S3-KCl glasses.
      That K+ ions in the form of Cl as the nearest coordination were homogeneously
      dispersed in the polymeric network was confirmed by the Raman spectra evolution
      of samples on the serials I and Ill. Raman spectral evolution of three
      composition serials can be successfully interpreted using a localized model
      considering the effect of K+ ions on the structural units GaS3/2 Cl and Ga2 S4
      Cl2.

PMID- 15852816
TI  - [Raman spectroscopic analysis of dissolution and phase transformation of
      chloropinnoite in the boric acid aqueous solution].
AB  - Raman spectroscopy of dissolution and transformation of chloropinnoite in 4.5%
      (w.t.%) boric acid aqueous solution at 30 degrees C has been recorded. The Raman
      spectra of kinetics process have been obtained. The phase transformation product
      is kurnakovite (2MgO x 3B2O3 x 15H2O). The main polyborate anions and their
      interaction in aqueous solution have been proposed according to the Raman
      spectrum. Some assignments were tentatively given and the relations between the
      existing forms of polyborate anions and the crystallizing solid phases have been
      gained. A mechanisms of dissolution and crystallization reactions and the
      formation condition of kurnakovite in Qinghai-Tibet plateau were proposed and
      discussed.

PMID- 15852817
TI  - [Application of depth-analysis of confocal Raman micro-spectroscopy to
      chirography identification].
AB  - Depth analysis of confocal Raman micro-spectroscopy was applied to chirography
      identification. The result indicated that depth analysis has potential
      application to forensic science field, especially in longitudinal identification
      of ink and inkpad. No matter what the spatial distributions of the signature pen
      and inkpad are, confocal Raman micro-spectroscopy can longitudinally distinguish
      those spatial differences. All those suggested that confocal Raman micro
      spectroscopy is a fast, simple, high sensitive and non-destructive technique.

PMID- 15852818
TI  - [Raman spectrum of nano-graphite synthesized by explosive detonation].
AB  - The nano-graphite powder synthesized by the detonation of explosives with
      negative oxygen balance is a new powder material with potential applications. In
      this work, the preparation of nano-graphite powder in steel chamber by pure TNT
      (trinitrotoluene) explosives has been introduced. In the synthesis process, the
      protective gases in the steel chamber are N2, CO2 and Ar, and the pressure is
      0.25-2 atm. Raman spectrum of the nano-graphite was measured. The characteristic
      Raman band assigned to sp2 of graphite has been observed at about 1 585 cm(-1)
      with half-peak width of 22 cm(-1). The peak shifted to a higher frequency by 5
      cm(-1) compared with that of bulk graphite. The authors explain this blue shift
      phenomenon by size effect. The average size of nanographite from Raman
      measurement is 2.97-3.97 nm. X-ray diffraction (XRD) and transmission electron
      microscopy (TEM) were used to measure the structure and particle size of the nano
      graphite. The crystallite size of nano-graphite estimated from XRD andTEM are
      2.58 nm (acid untreated) and 1.86 nm (acid treated) respectively, which is in
      accord with the results of the measurement approximately.

PMID- 15852819
TI  - [Raman spectra of cell from breast cancer patients].
AB  - Raman spectra of normal and cancer cell from breast cancer patients a
      represented. It is reported that all of the Ramanlines become weak. The
      intensities of Raman lines 782 and 1 084 cm(-1) of DNA phosphate group and 1 155
      and 1 262 cm(-1) of deoxyribosephosphate decrease. The spectral lines 812 cm(-1)
      of A-type DNA and 979 and 668 cm(-1) disappear, and the 905 cm(-1) peak is
      shifted to lower frequency by 6 cm(-1). This means that the phosphate backbone of
      DNA is destroyed to a certain extent and the fissiparity of cancer cell can't be
      controlled effectively. In addition, the authors found a kind of Raman line 960
      cm(-1) concerning calcificationand sclerosis of cancer cell. The results indicate
      that Raman spectra may offer the experiment basis for the cancer diagnosis and
      treatment.

PMID- 15852820
TI  - [Preparation and properties of organobentonites].
AB  - The chemistry organobentonites were synthesized by means of the ionexchange
      reaction between single-octadecyl trimethyl ammonium chloride(SOAC), di-octadecyl
      dimethyl ammonium chloride (DOAC) , tri-octadecyl methylammonium chloride (TOAC)
      quaternary ammonium salts and sodium base bentonies, respectively. The authors
      used FTIR, X-ray diffraction diagram and DSC thermograms to characterate the
      structure of the modified bentonites, and discussed the effect of different
      quaternary ammonium salt on the properties of organobentonites. The results
      showed that ion of the surfactants had entered into the chip layer of the
      bentonites, and changed the hydrophilic environment of the chip layer into
      hydrophobic environment and increased the distance among the chip layer, all of
      these had laid a base for the preparation of the nanometer composite material of
      high polymer/bentonite.

PMID- 15852821
TI  - [Investigation of the (6, 1) and (7, 2) bands in the A 2IIi-X 2sigma+ red system
      of CN radical].
AB  - The CN radical was produced by Penning AC discharge of the mixture of trace
      acetonitrile (36 Pa) and helium (660 Pa) and the ro-vibrational spectra were
      measured by optical heterodyne magnetic rotation enhanced concentration
      modulation spectroscopy in the range of 16 850-17 480 cm(-1). 138 lines and 118
      lines were assigned to the (6, 1) and (7, 2) bands in red system A 2IIi-X 2sigma+
      of CN respectively, while others were due to (8, 3) band in CN red system and C2
      Swan band system. More accurate molecular constants of A 2IIi (v = 6, 7) state
      and perturbation parameters zeta and eta between A and X states were derived
      based on nonlinear least-square fitting, individually, by diagonalizing the
      effective Hamiltonian matrix involving the perturbation elements of two
      electronical states and the standard deviation of fitting was less than the
      experimental uncertainty 0.007 cm(-1), which implied the accuracy of our results.

PMID- 15852822
TI  - [Synthesis and photoluminescence properties of Tb(3+) -acetylacetone ternary
      complexes doped with La3+ or Y3+].
AB  - Four series of solid complexes including RE(x) Tb(1-x) (acac)3 phen and RE(x)
      Tb(1-x) (acac)3 bipy (RE = La, Y; x = 0, 0.10, 0.20, 0.30, 0.50, 0.70, 0.90,
      1.00) were synthesized. These complexes were characterized by IR spectra and XRD.
      Photoluminescence (PL) properties of these complexes were studied. The relation
      between their fluorescence intensities and the content of doped ions was also
      discussed. The experimental results show that the PL intensity of Tb3+ was
      sensitized by La3+ or Y3+ , and La3+ is better than Y3+ in enhancing the
      fluorescence of Tb3+. When x = 0.1-0.3, the fluorescence intensities of most
      doped complexes are stronger than their corresponding pure Tb3+ complex.

PMID- 15852823
TI  - [Studying on the relationship between the fluorescence occurring time and
      fluorescence summit wavelength].
AB  - The authors have detected the fluorescence characteristic of aromatic pollution
      material-anthracene by OMA and obtained its 3-D(time-wavelength-fluorescence
      intensity) fluorescence diagrams, three summit wavelengths's fluorescence time
      spectra, equal high spectra. By analyzing these spectra properties, the authors
      find that there is a clear order with the occurring time among the three
      fluorescence summit wavelengths (399 nm, 423 nm, 445 nm). Long fluorescence wave
      occurs earlier than short fluorescence wave. This solution is also analyzed and
      explained by atomic energy levels theory.

PMID- 15852824
TI  - [Preparation and fluorescence study of anthracene, perylene and 1
      aminoanthraquinone colloids].
AB  - Anthracene, perylene and 1-aminoanthraquinone colloids have been prepared by
      reprecipitation method. In comparison with the fluorescence emission spectra of
      colloids and molecules (in acetone solution), it was indicated that collids
      fluorescence spectra are red-shifted and easy emission. Base on the fluorescence
      emission and molecular structure theory, the authors conclude that these
      molecules overlap when they form particles. At the same time they are planar
      molecules. This results in the strong stacking electronic properties. So
      fluorescence excitation and emission become easy.

PMID- 15852825
TI  - [Study on the effect of aluminum (III) on NADH in the presence of NH4Ac in
      aqueous solution].
AB  - This paper studied the interactions of Al (III ) and dihydronicotinamide adenine
      dinucleotide (NADH) in nearly neutral aqueous solutions (pH 6.5) by means of UV
      Vis and 1H, 13C-NMR techniques. The results suggested that Al (III) interacts
      with NADH to form Al-NADH complexes by occupying the binding sites of phosphate
      oxygen atoms O(N)1 and O(A)1 and ribose ring hydroxyl groups, which are the
      potential recognition sites for substrates, coenzyme and enzyme. In the presence
      of NH4Ac salt buffer and with Al (III) salt solution, NADH will be marked with
      structural changes at the nicotinamide moiety in contrast with almost no
      structural changes in Tris-HCl buffer solution with Al (III) salt.

PMID- 15852826
TI  - [UV-Vis spectroscopic study of aluminum-manganese cooperative effect on the
      melanin formation from DOPA oxidation].
AB  - The effect of aluminum and manganese ions on the melanin formation from oxidized
      DOPA was investigated by UV-Vis spectroscopy. In the weak acidic buffer solution
      (pH 5.5), aluminum and manganese ions have cooperative effect on the melanin
      formation. Aluminum is not a transition metal and therefore cannot initiate
      oxidative effect. However, manganese ions initiate the oxidation of DOPA to yield
      dopachrome. Aluminum ions can greatly catalyze the conversion reaction of
      dopachrome to form 5,6-dihydroxyindole, which is a key step in the biosynthesis
      of melanin. Its product is further oxidized and polymerized immediately to
      produce melanin. Therefore, the cooperative effect of manganese and aluminum ions
      increases the melanin formation from DOPA and enhances the oxidative stress.

PMID- 15852827
TI  - [Ultraviolet absorption spectra of iodine, iodide ion and triiodide ion].
AB  - Ultraviolet absorption spectra of iodine I2, iodide ion I(-) and triiodide ion
      I3(-) were studied, and molar absorptivities of these species were determined.
      Absorption spectrum of I2 aqueous solution appears as an absorption peak at 203
      nm with a molar absorptivity of 1.96 x 10(4) L x mol(-1) x cm(-1). Absorption
      spectrum of I(-) appears as two absorption peaks at 193 and 226 nm with molar
      absorptivities of 1.42 x 10(4) and 1.34 x 10(4) L x mol(-1) x cm(-1),
      respectively. When I2 aqueous solution is mixed with KI solution, two absorption
      peaks appear at 288 and 350 nm, respectively, indicating the formation of I3(-).
      Using saturation method, molar absorptivities of I3(-) at 288 and 350 nm were
      determined to be 3.52 x 10(4) and 2.32 x 10(4) L x mol(-1) x cm(-1),
      respectively.

PMID- 15852828
TI  - [Determination on conditional equilibrium constants of the complexes of Gd(III)
      and Yb(III) with HBED by UV difference spectra].
AB  - In 0.01 mol x L(-1) Hepes, pH 7.4 and at room temperature the binding of HBED
      with Gd(III) or Yb(III) was monitored by UV difference spectrum. The results show
      that the molar ratio of the complexes is most likely 1 : 1. Gd-HBED or Yb-HBED
      complex produced peaks at 237 nm and 291 nm. The molar absorptivities of Gd-HBED
      and Yb-HBED at 237 nm are deltaepsilon(Gd) = (22.52 +/- 0.20) x 10(3) cm(-1) x
      mol(-1) x L, deltaepsilon(Yb) = (27.15 +/- 0.11) x 10(3) cm(-1) x mol(-1) x L,
      respectively. The conditional equilibrium constants for the complexes were
      measured to be lgK(Gd-HBED) = 13.56 +/- 0.28 and lgK(Yb-HBED) = 16.06 +/- 0.03. A
      linear free energy relationship for the complexes of Yb(III) and Gd(III) has been
      established by using equilibrium data on 18 complexes. The HBED binding constants
      for Yb(III) and Gd (III) are in agreement with the linear free energy
      relationship.

PMID- 15852829
TI  - [Spectrophotometric determination of albumin with acid brown SR].
AB  - A new method for the determination of albumin in human serum and mouse serum has
      been developed by spectrophotometry coupled with acid brown SR(ASR) as probe
      molecule. The maximum absorption wavelength of ASR was at 445 nm, while the
      maximum absorption wavelength of their product was at 610 nm. However, the
      reaction of ASR with albumin such as BSA or HSA was so strong that parts of their
      product were undissoluble in water. The addition of gum water into the system
      effectively eliminated the deposition. Under optimum reaction conditions, the
      ranges of working lines for BSA and HSA were 0-91.0 mg x L(-1) and 0-95.2 mg x L(
      1), respectively. The detection limits were 5.72 mg x L(-1) for BSA and 5.15 mg x
      L(-1) for HSA. The relative standard derivation and the recovery of the method
      for the determination of total proteins in 6 human serum samples were 1.8%-4.4%
      and 93.6% - 109.1%, respectively. The proposed method has been employed in the
      assay of protein of human serum and mouse serum. The results of this work were in
      agreement with those obtained by Biuret method.

PMID- 15852830
TI  - [Review of atomic spectroscopy].
AB  - The content of this review covers atomic absorption spectroscopy, atomic
      fluorescence spectroscopy, atomic emission spectroscopy, inductively coupled
      plasma mass spectroscopy, sampling systems and preconcentration systems of
      spectrochemical analysis, speciation of inorganic elements, process analytical
      chemistry, and sensors of inorganic elements.

PMID- 15852831
TI  - [Temperature-dependence emission properties of Eu(3+)-doped in LiNbO3 single
      crystal].
AB  - The temperature-dependence emission spectra of lower and upper part of Eu(3+) 
      doped LiNbO3 crystals from 77 to 600 K were investigated under the excitation of
      a 488 nm light. The results show that, for upper part of crystal, the
      fluorescence intensity of Eu3+ ions increases with the temperature increase,
      however, for lower part, the intensity first increases with the temperature
      increase, and then decreases obviously with temperature increase. The variations
      of fluorescence intensity for lower and upper part of crystals are explained. The
      emission intensity of Eu3+ ions in LN is the total effect of thermally excited
      emission, phonon-assistant absorption and temperature-quenching effect.

PMID- 15852832
TI  - [Emission spectra of hydroxyl radical generated in air corona discharge].
AB  - In this paper, the relative emission intensity of the 309 nm transition band of
      hydroxyl radical (OH) was measured by a CCD imaging spectrometer in a pin-plane
      corona discharge scheme of one atmosphere pressure air injected with unsaturated
      water vapor from the central hole of the used pins. The influences of several
      factors on the OH radical production were investigated by relative emission
      intensity measurement. The production of OH radical increased with a limited
      increment of water vapor concentration in the mixed gas. Compared with positive
      DC corona discharges, more OH radicals were generated in positive pulsed corona
      discharges and less in negative DC corona discharges. The spatial distribution of
      OH radical production was also observed. Most OH radicals were produced within
      the range of 5 mm off the discharge pin electrode. In conclusion, this means of
      optical emission spectroscopy, compared with more sophisticated laser
      fluorescence measurements used for plasma OH production diagnostics
      investigation, is simpler and more effective for characterizing the OH radical
      potential for pollutant oxidation.

PMID- 15852833
TI  - [Quantitatively determining trace elements Co and Bi in gelatin by inductively
      coupled plasma atomic emission spectrometry method--applying IEC model to correct
      the spectral interference of Fe to Co].
AB  - By ICP-AES, the authors established the method to quantitatively determine the
      trace elements Co and Bi in gelatin. The authors processed the unknown sample
      with wet digesting method. Trace elements in gelatin could be quantitatively
      determined at the same time. To correct the spectral interference of Fe to Co at
      specific wavelength, the Interelement Correction(IEC) model was established. The
      results of the experiment showed that the IEC model could effectively erase the
      spectral interference of Fe to Co. The result of the spectral correction was
      greatly superior to the result where the spectral interference weren't corrected
      by the IEC model. The method was accurate, quick with high performance and wide
      linear range. The linear correlation coefficient of the tested elements was over
      0.999 90. The relative standard deviation (RSD%) was less than 2.00%. The
      recovery rates were in the range of 98%-107%.

PMID- 15852834
TI  - [Determination and correlation analysis of trace elements in hair of dependence
      drug addicts].
AB  - The concentrations of Al, Ba, Ca, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Sr and Zn in
      the human hair of dependence drug addicts and healthy contrast were determined by
      ICP-AES. The RSD of the method was 1.3%-4.9%, and recovery was 89%-129%.
      Correlation of the trace elements was analyzed by SPSS software. The contents of
      Zn and Ca in the hair of dependence drug addicts were lower, while those of Pb,
      Fe and Mg were higher than healthy contrasts. The result provided a foundation
      for improving immune function of dependence drug addicts and enhancing the effect
      of giving up taking addictive drugs.

PMID- 15852835
TI  - [Visible spectra analysis on edge recycling in HT-7 tokamak].
AB  - The main efforts of HT-7 superconducting tokamak were directed to quasi-steady
      state discharges and their relevant physics. Significant progress in obtaning
      high-performance discharges under quasi-steady state in HT-7 has been realized.
      The long pulse discharges have been obtained with a duration up to 63.95 s. The
      edge recycling was studied by the ratio of H to D through OSMA (Optical
      Spectroscopy Multichannel Analyzer) system. During the discharge, recycling
      dominated the particle balance. In the steady state, when the density was
      controllable, the deuterium(hydrogen) recycling played an important role and the
      recycling coefficient R < or = 1. During the later time, R >1 and the density was
      uncontrollable. The main contribution was from the D(H) recycling and impurity
      from the surfaces of the limiter and the first wall due to the increased surface
      temperature and radiation power, and these limited the duration of long duration
      discharges. The influence of wall conditioning on the edge recycling was also
      studied through the ratio of H to D.

PMID- 15852836
TI  - [A new de-noising technique for spectra based on Mexican hat wavelet].
AB  - Signals in spectral analysis often have random noise, which has negative
      influence on the accuracy and detection limit of analysis. A new chemometrics
      method named Mexican Hat Wavelet De-noising Arithmetic (MWDA) is presented, which
      can be used to remove noise in analytical chemical signals. In this method,
      Mexican Hat wavelet is chosen to construct de-noising function because of its
      excellent properties, then the de-noising function is used to extract useful
      information from noisy signals. MWDA is effective for signals with either wide
      peaks or very sharp peaks. Many processing results of simulated and experimental
      signals indicate that MWDA is a simple and powerful de-noising method, even when
      the signal has very high noise (whose signal to noise ratio is 1). After
      processed, the relative errors of peak position, peak height and peak area are
      less than 0.2%, 3.2% and 1.1% respectively. When it is applied to experimental
      spectra, the results are also satisfactory. This new method can increase the
      accuracy of spectral analysis, and the result is credible and satisfying.

PMID- 15852837
TI  - [Determination of relative error of pressure-broadening linewidth for the
      experimentally indistinguishable overlapped spectral lines with Voigt profile].
AB  - The simulation and fitting of the overlapped spectral lines with Voigt profile
      were presented in this paper. The relative errors epsilon of the fitted pressure
      broadening linewidth when taking the overlapped spectral line as one spectrum
      were discussed in detail. The relationship between such error and the two
      spectral lines center distance deltav0, and theoretical pressure-broadening
      linewidth deltav(L)0 were analyzed. Epsilon is found to be very large and the
      relationship between epsilon and deltav0, deltav(L)0 is very complicated when the
      value of pressure-broadening linewidth is considerably less than that of
      Dopplerian one deltavD. When deltav(L)0 is comparative to deltaVD the
      relationship between epsilon and deltav0 is close to the smooth two-order
      polynomial curve. However, the slop of this curve is negative while deltav(L)0 is
      smaller than deltavD and is positive when larger. Generally, epsilon decreases
      with the increase of proportion of deltav(l)0 to the whole spectral linewidth.
      All the above conclusion and corresponding data are the significant reference to
      determine the precise pressure-broadening coefficient from the experimentally
      indistinguishable overlapped spectrum, as well as to correct the fitted pressure
      broadening linewidth.

PMID- 15852838
TI  - [The influence of dissolved oxygen on sonoluminescence].
AB  - Abstract Ultrasound at frequency of 1.1 MHz was used to study the
      sonoluminescence(SL) in air-saturated water at temperature ranging from 283 to
      313 K. It was found that the logarithm of the detected SL intensity increases
      linearly with the dissolved oxygen (DO) concentration. The waters with five kinds
      of anions in different concentration (mg x L(-1)): Cl(-) (5-25), NO3(-) (0.2
      1.8), F- (0.1-2.7), HCO3(-) (8-15), SO4(2-) (0.4-40) were used to simulate
      natural environmental chemistry background. The experimental results show that
      the anions in the simulated water have no influence on the SL intensity.

PMID- 15852839
TI  - [Adopting the method of correlation coefficient to improve the accuracy of the
      xylene isomer's prediction model].
AB  - This paper focuses on the detailed researches on the correlation coefficient in
      near infrared spectrum and points out its characteristics in multi-component
      solution; the paper also proves the principle of obtaining more accurate results
      when using high correlation coefficient for model building, and presents a
      practical experiment to test the conclusions by using para-xylene, meta-xylene,
      and orthoxylene's mixture.

PMID- 15852840
TI  - [Spectroscopy of alpha-isoxazoleazoxyl-beta-diketone derivatives and their
      tautomers].
AB  - In this paper, the IR and UV-Vis spectroscopy of five novel alpha-isoxazoleazoxyl
      beta-diketone derivatives with different structures have been studied, and their
      keto-enol and azo-hydrazone tautomeric phenomena have been discussed. It was
      found that all compounds, which are in the solid or in the solution, exist in the
      form of hydrazodiketo and azoenol isomers. The authors can also see that there
      are two absorption bands which are in the range 246-262 nm and 326-339 nm,
      respectively, for all compounds in the UV spectra, and the intensities of long
      wavelength absorption bands which are attributed to azoenol forms are stronger
      than short wavelength absorption bands which are attributed to hydrazodiketo
      forms. This shows that the quantities of azoenol forms in the compounds are more
      than hydrazodiketo forms, and it may be due to that the varieties of the azoenol
      isomers can easily form six-membered rings structure in the form of
      intramolecular hydrogen bonding, and make chemical structures more stable.

PMID- 15852841
TI  - [Synthesis of a novel rare earth light conversion agent and study on its
      compatibility in plastics].
AB  - 2-octyl-1, 3-diphenol-1, 3-propdione was synthesized by phase transfer catalysis
      and its Sm complexes were prepared. These compounds were characterized by IR, EA,
      UV and 1H NMR; Sm complex and its mixture doped with PE and PVC show
      photoluminescence at 650 nm. There is excellent compatibility between Sm complex
      and plastics by the addition of long carbon chain. Therefore, Sm complex with
      long carbon chain is a superior light conversion agent with good compatibility in
      resins with emission wavelength suitable to the 643 and 660 nm for plants'
      photosynthesis.

PMID- 15852842
TI  - [Studies on properties of aggregates and Langmuir-Blodgett films for
      centrosymmetric naphthalocyanine molecules].
AB  - Deposition of Langmuir-Blodgett films and the aggregative properties of three
      centrosymmetric naphthalocyanine derivatives were investigated by using linear
      absorption spectra. Good LB films could be formed for all the three compounds. In
      dilute solution,the monomers are the main formation for the tetra-tert-butyl-cyan
      naphthalocyanine. Due to atomic zinc action, the tetra-tert-butyl
      naphthalocyanine zinc molecules could not only form H-aggregates, but also form J
      aggregates. The tetra-tert-butyl naphthalocyanine zinc molecules mainly are
      aggregates in dilute solution. In the Langmuir-Blodgett films, both tetra-tert
      butyl-cyan naphthalocyanine and tetra-tert-butyl-cyan naphthalocyanine zinc
      formed H-aggregates. The monomers are the main formation for the bi-( tetra
      tertbutyl-naphthalocyaninato)-orbium in dilute solution and Langmuir-Blodgett
      films.

PMID- 15852843
TI  - [Wavelet transform zero-crossing method for auto-extraction of spectral lines].
AB  - Wavelet transform method is used in this paper. The authors firstly studied the
      properties of spectral lines in the wavelet domain. By introducing the items of
      up-zero-crossings and down-zero-crossings, the authors concluded that absorption
      lines and emission lines correspond to different kinds of zero-crossings.
      Therefore the authors presented a new wavelet transform zero-crossing method for
      the extraction of spectral lines and the normalization of continuum spectra. The
      useful spectral lines can be obtained together with the continuum spectra. The
      extraction of spectral lines in this paper is a direct method, which avoids the
      errors caused during the process of noise reduction. The experiments both on
      stars and nearby galaxies show that our method can be used to accurately extract
      the spectral lines, which is helpful to the computation of characteristic
      parameters and the automatic classification of spectra based on spectral lines.

PMID- 15852844
TI  - [The properties of energy upconversion of Yb(3+) -doped materials based on ZrF4].
AB  - There have been few reports on studies of energy upconversion from Yb(3+) -doped
      materials based on oxide, fluoride or oxyfluoide, because researches commonly
      considered that Yb3+ was only a good sensibilizer. This paper reports the
      properties of energy upconversion of Yb(3+) -doped materials based on ZrF4. The
      rare earth Yb3+ was doped in the ZrF4 glass under the specific condition. Using
      980 nm laser as an excitation light, the upconversion fluorescence spectra of the
      sample were measured, and the red band, green band, blue band and purple band
      observed, respectively. The peaks were at 412, 478, 558 and 671 nm, respectively.
      This paper reports the upconversion from Yb3+ standard energy level to Yb3+
      energy level 2 F7/2.

PMID- 15852845
TI  - [Comprehensive analysis of up-conversion luminescence saturation phenomena of
      ErYb:oxyfluoride vitroceramics].
AB  - The saturation phenomenon of the up-conversion luminescence of erbium ytterbium
      co-doped oxyfluoride vitroceramics (ErYb:FOV), when excited by a 966 nm diode
      laser, was investigated comprehensively in the present article. A new kind of
      "characteristic saturation phenomenon", which results from energy diffusion, was
      found, i. e. the slope of logI-logP curve, the double logarithmic variation of up
      conversion luminescence intensity I upon laser power P, is increased evidently
      toward regular multi-photon relation with the increase of laser facula. The
      "typical saturation phenomenon" resulting from ground state population's
      exhaustion has huge influence as well, which causes these logI-logP curves to
      bend gradually with the increase in laser power. Interestingly, this "typical
      saturation phenomenon" can be decreased obviously and even vanishes when the
      pumping laser power density is decreased enough.

PMID- 15852846
TI  - [Theoretical analysis of wavelength choice in tri-wavelength method of
      temperature measurement].
AB  - In this paper, a non-dimensional emissivity model with universality is
      established. For the tri-wavelength method of temperature measurement, based on
      the non-dimensional emissivity, the applicable measurement condition and
      theoretical analysis of wavelength choice are mainly introduced. In the
      discussion of theoretical analysis of wavelength choice, by optimizing the
      analysis of measurement method and the concept of isothermal line induced by the
      measurement coordinates, two kinds of ideal choice rules of measurement
      wavelength are put forward, which will be necessary to the technology application
      of this tri-wavelength method. Meanwhile the optimizing idea is also applicable
      to multi-wavelength method of temperature measurement.

PMID- 15852847
TI  - [Collisional excitation transfer between Na2(B 1pi(u)) and Na2(2 1sigma(g)+)].
AB  - The B 1pi(u) electronic state of Na2 was excited by the 441.6 nm He-Cd laser
      line. The Na atomic transitions and the A 1sigma(u)+ --> X 1sigma(g)+ band of Na2
      were recorded. From the intensities and spectra of the Na and Na2 fluorescence
      several collisional processes in the excited sodium atom-dimer system were
      identified. The Na atomic lines are the result of collisional energy transfer
      from Na2 (B 1pi(u)) to Na(3P). Predissociation process may also contribute to
      atomic fluorescence. The A 1sigma(u)+ --> X 1sigma(g)+ band is interpreted
      through a populating mechanism involving collisional transfer from B 1pi(u) to 2
      1sigma(g)+ followed by a radiative transfer to the A 1sigma(u)+ state. From the
      decay constants and fluorescence intensities, the rate coefficient at 360 degrees
      C for collisional energy transfer from Na2 (B 1pi(u)) to Na2 (2 1sigma(g)+) was
      found to be 5.7 x 10(-10) cm3 x s(-1). The predissociation rate of the B 1pi(u)
      is 2.7 x 10(6) s(-1).

PMID- 15852848
TI  - [Electronic spectral study on salicylaldehyde-amino acid Schiff bases in water].
AB  - Seven salicylaldehyde-amino acid Schiff bases in water were investigated by means
      of electronic spectra, which is helpful to investigate the label of radionuclides
      with the seven ligands in water for radiopharmaceutical study. Except 10(-5) mol
      x L(-1) for Sal-tyr, the minimum concentration of formation is 10(-4) mol x L(-1)
      for all other Sal-aas. Only Sal-his is generated at pH 9-10, while the minimum pH
      conditions for formation are 8 for Sal-gly and Sal-tyr, and 9 for other four. All
      Sal-aa but Sal-cys, whose concentration at 36 h is higher than that of newly
      produced one, decompose gradually since generation, with existing time of 24 h
      for Sal-gly and Sal-glu, and 48 h for other four.

PMID- 15852849
TI  - [Investigation on the spectral characteristics and existing state of a
      substituted 3H-indole molecular probe in triton X-100 reverse micelle].
AB  - The interactions between a fluorescent molecular probe, i. e., [2-(p-hexylamino)
      phenyl-3, 3-dimethyl-5-ethoxycarbonyl-3H-indole] methyldioctadecylammonium iodide
      (A) and Triton X-100/heptane/hexanol/water reverse micelle have been investigated
      by spectroscopy. Micropolarity of the environment, fluorescence anisotropy
      parameter and the pH effect of A in Triton X-100 reverse micelle were determined.
      Furthermore, the state of water in reverse micellar systems was studied by FTIR.
      According to the above experimental results, some information on the structure of
      Triton X-100 reverse micelle was obtained and the probable site of A in this
      system was discussed.

PMID- 15852850
TI  - [S2-->S0 radiative transition of 2,2'-bipyridine doped in silica gel glass].
AB  - Doping 2,2'-bipyridine molecules in silica gel glass leads to special
      spectroscopic properties compared to those dissolved in liquid solutions. For the
      sample without heat treatment, two broad bands centered at 400 nm and 454 nm
      respectively, induced by the radiative transition from the first excited level S1
      to the ground level S0 and attributed to the emission from an excited dimeric
      2,2'-bipyridine species respectively, were observed. After heat-treated at 200
      degrees C, the excimer emission at 454 nm disappeared, and the sample exhibited
      another emission band centered at 325 nm due to the radiative transition from the
      second excited level S2 to the ground level. S2-->S0 transition resulted from
      restricting 2,2'-bipyridine molecules in silica networks. Only the structure
      emission of S2-->S0 transition was observed when heat-treated at 550 degrees C,
      which indicates that most of 2,2'-bipyridine molecules were entrapped in the
      cages of Si-O network. The above results can be used to characterize the
      microstructural evolution of hybrid organic-inorganic optical materials.

PMID- 15852851
TI  - [Determination of nitrite in water samples by sequential injection analysis with
      chemiluminescence detection on chip flow cell].
AB  - A sequential injection chemiluminescence's system using a chip flow cell was
      described for the determination of trace amount of nitrite in water samples.
      Nitride reacted with hydrogen peroxide to form peroxynitrous acid in sulfuric
      acid medium, which was an unstable in acid medium and subsequently was quenched
      into peroxynitrite in basic solution. During the composition of peroxynitrite the
      chemiluminescence intensity was enhanced with the presence of uranin and
      ethyldimethylcetylammonium bromide. The reaction coil (flow cell) and holding
      coil was combined for tracking the emission signal. The experimental parameters
      including physical and chemical parameter were optimized. The interference of
      cations in water samples was eliminated by passing previously the sample solution
      through a cation-exchange column. The linear range of the calibration graph was
      obtained from 1 x 10(-6) to 1 x 10(-4) mol x L(-1) with a correlation coefficient
      of 0.9998. The detection limit at 95% confidence was 6.8 x 10(-7) mol x L(-1).
      The relative standard deviation at 1 x 10(-5) mol x L(-1) nitrite level was 2.7%,
      and the recovery of 90%-99% and the sampling frequency of 80 h(-1) were obtained.

PMID- 15852852
TI  - [Studies on the effects of steric hindrance of guest molecule on the formation of
      inclusion complexes by molecular luminescence].
AB  - Fluorescence and room temperature phosphoresce (CD-RTP) induced by cyclodextrin
      methods were employed to investigate the effects of steric hindrance of guest
      molecule on the formation of inclusion complexes of beta-cylcodextrin (beta-CD)
      and bromonaphthalene (BrN). It has been found that the RTP intensity of 2
      BrN/beta-CD/n-Bu/ph was less than one third of that of 1-BrN/beta-CD/n-Bu/ph and
      fluorescence emission spectra of 2-BrN/beta-CD/n-Bu/ph had a red shift of 5-10 nm
      comparing with that of 1-BrN/beta-CD/n-Bu/ph under the optimum experimental
      conditions, respectively. These results exhibited that the steric locations of
      bromine in BrN strongly influenced the formation of inclusion complexes. The
      determination of the two quadri-inclusion complexes constants further
      demonstrated that the steric hindrance has a great effect on the formation of
      inclusion complexes. According to the above experimental results, the mechanism
      of formation of inclusion complexes were discussed briefly.

PMID- 15852853
TI  - [Determination of total effective value of flavonoids in propolis by quenched
      electrochemiluminescence analysis].
AB  - Propolis is a kind of quality health foodstuff containing flavonoids, which is an
      important clinical effective component in many Chinese traditional medicines. The
      flavonoids could be used to reduce or clear free radicals, which manifests its
      medical functions. But there are no satisfactory methods to analyze the content
      of flavonoids in propolis. This paper reports a new method to determine the total
      effective value of flavonoids in propolis based on quenched effect for iodide
      catalyzed electrochemiluminescence of luminol. It is a sensitive and simple
      method and might be a probable approach to examining the quality of propolis
      products.

PMID- 15852854
TI  - [The determination of glutathione by electrochemiluminescence quenching method].
AB  - Glutathione is an important active substance in organisms. Its study and
      determination are very significant to human being's health and life. In neutral
      medium, the quenching effect of reduced glutathione on the
      electrochemiluminescence of luminol-iodide was studied in this paper. Therefore a
      novel sensitive method for the determination of reduced glutathione was developed
      based on it. The linear response range of this method is from 3.38 x 10(-13) mol
      x L(-1) to 4.72 x 10(-3) mol x L(-1). This method is the most sensitive one and
      its linear range is the widest among those reported in the literature.

PMID- 15852855
TI  - [FTIR spectroscopic explorations of clinical practice of breast cancer].
AB  - The authors detected ten normal breast tissue samples and eight breast cancer
      samples by FTIR spectroscopy with an ATR probe. Nineteen variables of thirteen
      bands in the spectra were compared using standard statistic methods. The results
      demonstrated that bands of protein, lipid, carbohydrate, and nucleic acid from
      cancerous samples were significantly different from those from normal ones: (1)
      The relative intensity of N-H band increased and amide I band shifted to lower
      wave number significantly; (2) Symmetric and antisymmetric vibrations of -CH2
      group, C=O vibration, and relative intensity of (-CH2)n decreased; (3) The
      intensity of 1160 cm(-1) band was much weaker than that of 1120 cm(-1); (4) The
      band of P=O or P-O-C shifted toward lower wave number. The authors believe that
      FTIR spectroscopy has a promising future in breast cancer diagnosis.

PMID- 15852856
TI  - [Studies on spectral characteristics of solid propellant by remote sensing FTIR].
AB  - The infrared spectral characteristics of high-intensity IR solid propellant were
      measured in this paper using a Bruker EQUINOX55 remote sensing FTIR spectrometer.
      The emission spectra of the combustion flame were recorded in the range of 4700
      1800 cm(-1) with a spectral resolution of 4 cm(-1). The combustion temperatures
      of solid propellant at the burning time of 0, 9, 18, 27 and 36 s calculated from
      the molecular rotation-vibration spectra were 1992.5, 1610.9, 2294.4, 2361.1 and
      1916.9 K, respectively. Moreover, the spectral radiance distributions of the high
      IR flare material at different times were given, and the combustion product
      concentrations of HCl, HF, CO2 and CO were determined quantitatively. Results
      showed that remote sensing FTIR is a potential technology that can be applied to
      the measurement of IR spectral characteristics, especially to the identification
      of the IR objects, guidance and anti-guidance in the military, and the
      modification of the make-up of solid propellant.

PMID- 15852857
TI  - [In situ FTIR spectroscopic studies of the catalytic combustion of acid red B on
      CuFe2O4 in the presence and absence of O2].
AB  - The reaction process of catalytic combustion of ARB on CuFe2O4 in the presence
      and absence of O2 was studied by in situ DRIFT spectroscopy. The results showed
      that the decomposition of the sulfonic group of ARB molecule was not affected by
      the reaction atmosphere, but the decompositions of azo group and aromatic ring
      were markedly affected by the presence or absence of O2. The catalytic combustion
      of ARB was faster in air atmosphere than that in N2 atmosphere, and ARB could be
      completely oxidized to CO2 and nitrate at 300 degrees C. But in N2 atmosphere, it
      was very difficult for the decomposition of ARB to complete at 300 degrees C,
      even though air was introduced following this process. The temperature required
      for the rapid and complete decomposition would be as high as 500 degrees C.

PMID- 15852858
TI  - [Fast outlier detection for milk near-infrared spectroscopy analysis].
AB  - Near-infrared spectroscopy is a fast and efficient analytical technique based on
      multivariate calibration model, which correlates near-infrared spectra with the
      property of samples (such as concentration). The reliability of analytical
      results depends mostly on the accuracy of measured spectra. But outliers do not
      make for reliable data. The authors combined RHM (Resampling by Half-Means) with
      SHV (Smallest Half-Volume) method to detect the outliers of the near-infrared
      spectra of milk samples, and the results were satisfactory. The performance of
      the new method is superior to the traditional outliers detecting algorithms such
      as Mahalanobis distances and hat matrix leverage. And this combined method is
      simple and fast to use, conceptually clear, and numerically stable, so it is
      recommended to be used for the detection of multiple outliers in multivariate
      data, especially the online measurement and discriminant analysis.

PMID- 15852859
TI  - [Synthesis, spectral characterization and bioactivity of complexes of
      furoylpyrazolone-thiosemicarbazone].
AB  - A new Schiff base containing sulphur, 1-phenyl-3-methyl-4-(alpha-furoyl)
      pyrazolone-5-thiosemicarbazone (HL) and its Zn(II), Cd(II) and Co(II) complexes
      have been synthesized. On the basis of elemental analysis and molar conductance,
      the general formulae of the complexes, [ZnL2] x 1.5H2O, [CdL2] x C2H5OH and
      [CoL2] x H2O, were given. They were characterized by IR, UV-Visible, 1H NMR, 13C
      NMR and magnetic moments. The results show that the metal ions exhibit
      coordination of six in the complexes. The antibacterial experiments indicate that
      they have high antibacterial activities against S. aureus, B. subtilis, E. coli,
      E. carotovora, and C. flaccumfaciens.

PMID- 15852860
TI  - [Study on an unknown complex by gas chromatography/infrared spectrometry].
AB  - If the authors use normal infrared spectrometry, a lot of mixture compounds are
      difficult to characterize, because most of the peaks are overlapped in the
      spectra. Gas chromatography/Infrared spectrometry (GC-IR) are widely used in the
      separation and identification of organic complexes. The GC-IR can characterize
      the ingredients quickly and correctly that are difficult to do for normal
      infrared spectrometry. The technique also can be used to quantitatively analyze
      the ingredients by integral. The authors studied an unknown complex by GC-IR
      here.

PMID- 15852861
TI  - [High temperature Raman spectra and structure character study of BSO crystal].
AB  - The structure character of BSO crystal at room temperature was generalized. The
      main Raman shifts of lattice vibration at room temperature were interpreted. The
      Raman spectra of BSO crystal were measured in a temperature range from 293 K to
      1123 K with high temperature Raman spectroscopy and time-resolved detection
      techniques. Temperature-dependence character of the Raman spectra of the crystal
      was investigated. The vibration mode of the longest bond Bi-O(1) in crystal
      shifts from 542 cm(-1) to 512 cm(-1) with the temperature increasing from room
      temperature to 1123 K. It can be attributed to the fact that oxygen atoms are
      electrostatic bond to Bi atoms. The intensity of 88 cm(-1) modes, which belongs
      to combination mode of bending and stretching in Bi3O4 unit, changes not so
      noticeably as other modes, and even the 58 cm(-1) mode of Bi atoms motions in
      crystal lattice decreases rapidly when the temperature is higher than 873 K,
      which indicates that the framework structure of the crystal is broken down at
      high temperature, while the Bi3O4 unit still exists.

PMID- 15852862
TI  - [Spectroscopy studies on the interaction of bis(p-nitrophenyl) esters and beta
      cyclodextrin].
AB  - The bis(p-nitrophenyl) esters of succinic acid, adipic acid and sebacic acid have
      been synthesized, respectively, by employing 1,3-dicyclohexylcarbodiimide (DCC)
      as a dehydration agent. The composition and structure of the esters have been
      characterized by elemental analysis, FTIR, 1H NMR and DSC. Furthermore, the host
      guest interactions of the esters with beta-cyclodextrin (beta-CD) have been
      studied systematically by using fluorescence quenching, fluorescence spectroscopy
      and UV-Vis spectroscopy measurements. It was demonstrated that the chain of the
      esters was longer, the interactions was weaker between the esters and the beta
      CD. Both p-nitrophenyl groups in bis(p-nitrophenyl) esters of succinic acid can
      enter the inner cavity of beta-CD. In contrast, only one of the groups in bis(p
      nitrophenyl) esters of adipic acid can enter the cavity. For bis(p-nitrophenyl)
      esters of sebacic acid, however, both groups can not enter the cavity of the beta
      CD. The difference in the host-guest interactions of the three esters with beta
      CD has been attributed to the difference in the conformations adopted by the
      esters. Based upon these observations, it is proposed that the esters with short
      linker may be more suitable for construction of new networks, which are based
      upon, in concept, host-guest interactions.

PMID- 15852863
TI  - [Study on the interaction of anticancer drugs and DNA using fluorescence
      spectroscopy].
AB  - Fluorescence spectroscopy has achieved great successes in the study on the
      interaction of drugs and DNA in both quantitative analysis and qualitative
      analysis. While the fluorescence probe technique can be used to measure the
      intensity of drugs-DNA interaction, because the injected drugs can change the
      fluorescence intensity of the probe. In this paper, the authors use berberine as
      a probe to measure the interaction intensity between some anticancer drugs and
      DNA, calculate the constant D and determine the effects of those drugs. In
      addition, the authors point out that this method can not be efficient for certain
      drug solution.

PMID- 15852864
TI  - [Ultraviolet and blue-violet photoluminescence of gold nanoparticles].
AB  - Suspended gold nanoparticles (size range 20-30 nm) have been synthesized via
      electrochemical method. The emission spectra of gold colloidal nanoparticles were
      studied at room temperature. Fluorescence occurs at ultraviolet and blue-violet
      wavelengths. Two emission peaks were observed at 377 nm and 459 nm, respectively,
      when the corresponding excitation wavelength was at 220 nm. The emission peak at
      377 nm increases with increasing particle density or excitation intensity,
      whereas the emission peak at 459 nm decreases with decreasing excitation
      intensity or increasing the particle density, and disappears below the threshold.
      With increasing the slit width, the intensity difference between these two
      emission peaks decreases and the ratio approaches 1. All these observed results
      are in agreement with the theory of self-organized random micro-cavity. It is
      indicated that the fluorescence emissions in ultraviolet and blue-violet
      wavelength regions are induced by the multiple scattering in a disordered gold
      nanoparticles system. And these photoluminescence features suggest the possible
      future applications in the areas of optical data storage and full color display.

PMID- 15852865
TI  - [The research on the quenching of fluorescence spectra of TOP I by iodine anion].
AB  - Comparing the fluorescence spectra of tobacco peroxidase I (TOP I) solution and
      the solutions titrated by iodine anions, the number of binding locus and the
      binding constant of iodine anion to TOP I were calculated by using the modified
      Stern-Volmer equation. The mechanism of the quenching of fluorescence spectra and
      the distribution of tryptophane residues in the TOP I molecule were discussed.

PMID- 15852866
TI  - [Influence of excitation light wavelength on the fluorescence spectra of ethanol
      solutions].
AB  - Ethanol solution can emit visible fluorescence when induced by UV light. With
      emission spectral profiles similar on the whole, the peaks are red-shifted
      distinctly when the excitation light alters from 200 to 250 nm. And the spectral
      profiles of ethanol solutions with different concentrations are also red-shifted
      when induced by the same wavelength of excitation light. A thorough analysis of
      the rule of spectrum peaks that are red-shifted is carried out and discussed in
      theory and in experiment. Investigation on the intrinsic fluorescence spectrum of
      ethanol solution and its characteristics will contribute to the study of the
      fluorescence spectra when ethanol serves as a solute and hydrolysis catalyst.
      Especially, this study will also help to offer a sensitive method of the
      determination of ethanol.

PMID- 15852867
TI  - [Study on the interaction of Pb2+ and bovine serum albumin by fluorescence].
AB  - The interaction of Pb2+ and bovine serum albumin (BSA) was studied under
      conditions similar to those in human bodies by fluorescence spectra. The results
      indicated that tryptophan and tyrosine, which were located in BSA, had a max
      fluorescence emission peak at 341 nm with an excitation wavelength of 283 nm. It
      was shown that Pb2+ had a powerful ability to quench the BSA fluorescence with a
      mechanism of a static process rather than a dynamic one. The apparent quenching
      constant Kq was obtained to be 9.5 x 10(12) L x mol(-1) x s(-1) by Stern-Volmer
      equation. The apparent complexation constant of Pb2 x BSA is lgK = 11.61. The
      nitrogen in BSA could coordinate with lead in Pb2-BSA.

PMID- 15852868
TI  - [Inhibitory kinetic fluorimetric determination of trace aniline].
AB  - An inhibitory kinetic fluorimetric method is reported for the determination of
      trace aniline. The proposed method is based on the inhibitory effect of aniline
      on the reaction of potassium periodate oxidation of rhodamine 6G in phosphoric
      acid medium. The detection limit is 7.2 ng x mL(-1), the linear range of the
      determination is 0.010-0.183 microg x mL(-1). This method has been applied to the
      determination of trace aniline in phenolic tubes and water samples with
      satisfactory results.

PMID- 15852869
TI  - [Assay of three kinds of aluminum fractions (Al(a), Al(b) and Al(c)) in
      polynuclear aluminum solutions by Al-Ferron timed spectrophotometry and
      demarcation of their time limits].
AB  - Al-Ferron timed spectrophotometry assay is a basic method in the study on the
      formation of polynuclear hydroxyl aluminum species and their transformation laws
      in aqueous systems. In actual working process, this methodology has some
      dogmatism and arbitrariness in the time limits demarcation of the three kinds of
      aluminum fractions (Al(a), Al(b) and Al(c)) in polynuclear aluminum solutions,
      which makes this kind of classification rougher, and the experimental results non
      reproducible. The reason for this difference is that the specific species within
      Al(a), Al(b) and Al(c) have different reaction mechanism and dynamics, and that
      specific species of Al(b) having different OH/Al ratios have different reaction
      rates with ferron. In this paper, the ExpAssoc distribution was applied to
      quantitatively fit the Al-Ferron reaction dynamics curve, and the extrapolation
      method was used to survey the 1 min measured value [Al(a)] of monomeric Al, which
      is hard to obtain in manual manipulation. The time demarcation between Al(b) and
      Al(c) should reach the point of the experimental data curve up to horizontal
      platform. The microwave-radiated technology was used to fast assay the total
      aluminum concentration [Al(T)]. With these methods, the contents of monomeric
      Al(a), polynuclear Al(b) and gel Al(c) can be conveniently and quantitatively
      measured. It offers a novel method for surmounting the arbitrariness in the
      measurement of the three kinds of aluminum fractions and the repetitive
      calculation of Al(a) and Al(b).

PMID- 15852870
TI  - [Synthesis of 2,3,4-trihydroxyacetophenone hydrazones and study on their spectral
      properties].
AB  - 2,3,4-Trihydroxyacetophenone was synthesized with pyrogallol. Benzoylhydrazone
      and p-hydroxybenzoylhydrazone were synthesized using the reaction of ethyl
      benzoate and methyl p-hydroxybenzoate with hydrazine hydrate. Three novel 2,3,4
      trihydroxyacetophenone hydrazones were synthesized using the reaction of 2,3,4
      trihydroxyacetophenone with benzoylhydrazone, p-hydroxybenzoylhydrazone and
      phenylhydrazine. IR, UV and the fluorescence spectrum of 2,3,4
      trihydroxyacetophenone hydrazones were studied.

PMID- 15852871
TI  - [Analysis of spectral properties of oil matrix raw materials in skin care
      products].
AB  - There are many kinds of oil matrix raw materials used in skin care products.
      Their spectral properties are different. The matrix raw material that has better
      ultra-violet absorption will enhance the sun-screening agent effect obviously. In
      the present article the spectral properties of six oil matrix raw materials often
      used in skin care products were mainly measured and analyzed by
      spectrophotometer. The analysis of T-lambda spectra shows that castor oil can
      absorb ultraviolet as well as near infrared light. It was shown that castor oil
      chosen as the matrix raw material will improve the effect of sun-screening agent
      and enhance the products. The function of sun-screening agent and skin health
      care product will stand out clearly.

PMID- 15852872
TI  - [Speciation analysis of selenium by flow-injection catalytic spectrophotometry].
AB  - A new flow-injection catalytic spectrophotometric method was proposed for the
      determination of Se(IV) based on its catalytic effect on the reduction reaction
      of azure I by Na2S in pH 7.0 citric-acid sodium-hydrogen-phosphate buffer
      solution. Some different schematic diagrams of FIA were compared. Effects of the
      flow rates of reagents and sample, the medium and its acidity, the temperature,
      and coexistent substances were studied respectively. The amount of used reagents
      and the experimental conditions for sampling volume and coil length were
      optimized by using the controlled and weighed centroid simplex method. The Linear
      range of the determination is 0.1-2.0 mg x L(-1), the detection limit is 0.015 mg
      x L(-1), the relative standard deviation is less than 3.1%, and the sampling
      frequency is 120 samples per hour. The method has been applied to the
      determination of organic selenium and inorganic selenium in garlic and selenium
      yeast. It was found that garlic had a strong enriching effect for selenium, and
      the conversion ratio of organic selenium decreased with increasing the
      concentration of selenium in the environment. The recovery of this method is
      97.1%-104.3%.

PMID- 15852873
TI  - [Quantitative determination of total flavonoids in sea-buckthorn fruit juice by
      three wavelength spectrophotometry].
AB  - Numerous studies dealing with the quantitative determination of total flavonoids
      in sea-buckthorn fruit juice by spectrophotometry are presented. The flavonoids
      in sea-buckthorn fruit juice and aluminate produce stable complex whose
      absorption occurred at longer wavelength. To determine the total flavonoids in
      sea-buckthorn fruit juice by traditional spectrophotometry method, baseline shift
      and asymmetric absorption peak occurred on the absorption curve. Quantitative
      determination of flavonoids in sea-buckthorn fruit juice by three wavelength
      spectrophotometry method can eliminate the absorbance error caused interfering
      components in turbid solution and the scattering effect. Background changing with
      the concentration change and asymmetric absorption peak problems can also be
      solved. The regression equation of concentration vs deltaA was obtained: deltaA =
      - 0.00703 + 0.00048c with a relation coefficient gamma = 0.9991. The experimental
      results demostrate the total flavonoids concentrations in 0-800 microg x mL(-1)
      with deltaA obeying linear relation when the absorbance was measured at
      wavelength lambda1 = 495 nm, lambda2 = 415 nm and lambda3 = 368 nm. The recovery
      is 97.0%-101.0% and the coefficient of variation is 0.058% (n = 9). The method is
      more advantageous than tranditional spectrophotometry method.

PMID- 15852874
TI  - [Study on the measurement of residual stresses around indentations in SiC/Al2O3
      nanocomposite using fluorescence].
AB  - The residual stresses induced by an indentation were studied in 5% SiC/Al2O3
      nanocomposite using fluorescence spectroscopy in this work. It was found that
      within the indentation and the region of about 10 microm outside the impression,
      the broadening of the R-lines is obvious, and that the compression shift is a
      strong function of the distance from the indentation centre. From the observed
      frequency shifts, the hydrostatic stresses in regions sampled in the indentation,
      and in the complex stress field surrounding it were measured. The same variation
      regularity of stresses exists along the diagonal direction and the side vertical
      bisector direction. The symmetry of the residual stress field around the
      indentation was also found.

PMID- 15852875
TI  - [Preparation of Ce-loaded nano-TiO2 and study on its UV-Vis reflective spectrum].
AB  - Ce-loaded nano-TiO2 was prepared by the loading technology of metallic ions, and
      was characterized by XRD and TEM. The UV-Vis reflective spectra of nano-TiO2 and
      Ce-loaded nano-TiO2 were analyzed. The result shows that after loading rare earth
      element Ce the reflective spectral characteristic of nano-TiO2 moves to the
      visible region with a red shift to 500 nm, and the obvious change takes place in
      the absorbance in the visible spectral range with a three-fold enhancement. It is
      indicated that the load of rare earth element Ce is favorable to enhancing the
      absorption of visible and UV light of anatase nano-TiO2, and thereby greatly
      increases its photocatalytic activity.

PMID- 15852876
TI  - [Ultraviolet spectral characteristics of charge-transfer reaction complex in
      micellar system and its application].
AB  - Charge-transfer (CT) reaction of chloranil (TCBQ) as a pi-electron acceptor with
      fleroxacin (FLX) as an electron donor has been studied by ultraviolet
      spectrophotometry method. Experiment showed that FLX reacted with TCBQ in sodium
      dodecyl sulfate (SDS) micellar systems, and a stable complex was formed and the
      absorbency was remarkably enhanced. Therefore, a simple, rapid, accurate and
      sensitive method for the determination of FLX has been developed. Beer's law is
      obeyed in the range of 0.6-24 mg x L(-1) of FLX and r = 0.9993. The apparent
      molar absorptivity of CT complexes at 326 nm is 3.3 x 10(4) L x mol(-1) x cm(-1).
      The composition of CT complex was found to be 1:1 by Bent-French and curved
      intersection methods. The proposed method has been applied to the determination
      of ESL in tablets. The recoveries are 99.2%-99.7%. The relative standard
      deviation is 0.7%-2.1%. The proposed methods are suitable for the routine quality
      control of drug alone and in tablets or capsules without fear of interference
      caused by the excipients expected to be present in tablets or capsules.

PMID- 15852877
TI  - [Determination of twenty one elements in lithium hexafluorophosphate by ICP-AES].
AB  - One gram (+/- 0.0001 g) of lithium hexafluorophosphate was weighed exactly under
      dry atmosphere and was dissolved with an adequate amount of dimethyl carbonate
      (DMC). After the sample solution was pretreated with a series of methods, Be, Cu,
      Pb, Ca, Zr, Co, Mg, V, Ti, Mo, Ni, Mn, Sr, Zn, K, Al, Ba, Cd, Fe, Cr and Na were
      determined by ICP-AES. The results show that the recoveries of standard addition
      were 93.3%-102.1%, and the relative standard deviations (n = 11) were 0%-3.56%.
      The method is efficient, accurate and easy to operate. It has been applied to the
      determination of lithium hexafluorophosphate products with satisfactory results.

PMID- 15852878
TI  - [Determination of trace zirconium and hafniumin sample by atomic emission
      spectrometry].
AB  - This paper describes the determination of trace Zr and Hf in the sample using
      carbon powder and titanium oxide as the buffer by Atomic Emission Spectrometry
      (AES). Titanium was selected for the internal standard line. Sample separation
      and chemical treatment were not required. The sample was directly loaded into an
      ordinary electrode. The method is simple, rapid and accurate. The conditions for
      the determination, and the factors of influence have been studied. A new method
      has been developed for the determination of zirconium and hafnium. The analytical
      lines of Zr and Hf were 327.3 and 286.6 nm respectively. The internal standard
      line of Ti was 308.8 nm. The linear range of the determination of Zr and Hf was 0
      0.50% and 0-0.25% respectively. The detection limit of Zr and Hf was 0.0010% and
      0.010% respectively. The range of the recovery of zirconium and hafnium was
      96.67%-105.0%. The results for these elements in standard sample are in agreement
      with certified values with a precision of 3.61% RSD for Zr (n = 9), and 4.82% RSD
      for Hf (n = 9). The method has been applied to the determination of Zr and Hf
      with satisfactory results.

PMID- 15852879
TI  - [Speciation analysis of mercury in traditional Chinese medicine by vapor
      generation atomic fluorescence spectrometry].
AB  - A sensitive method has been proposed for the determination of inorganic mercury
      and total organic mercury in traditional Chinese medicine (Wanshi Niuhuang
      Qingxin) by vapor-generation atomic fluorescence spectrometry. The experimental
      conditions that influence the atomic fluorescence signal intensity of Hg and the
      oxidization of organic mercury were investigated and optimized. Thiourea citric
      acid was selected as a sensitization agent, which greatly enhanced atomic
      fluorescence signal intensity of mercury. The influence of foreign ions and their
      elimination were studied. The detection limit of the method for Hg was 7.6 ng x
      L(-1) and the relative standard deviation was 1.56%-3.28% for Hg. The proposed
      method was successfully applied to the determination of mercury speciation in
      real samples with a recovery range of 90.3%-110.3%.

PMID- 15852880
TI  - [Determination of trace silver by flame atomic absorption spectrometry using
      chitosan enriching method].
AB  - A method for the determination of trace silver by flame atomic absorption
      spectrometry using chitosan enriching method has been investigated. The
      conditions that influence the adsorption of silver by chitosan were studied. The
      optimal flow rate of the sample solution was 1 mL x min(-1), and the optimal
      sorption (96.7%) was possible by using the systems with pH 6.0 for silver. The
      amount of saturated adsorption of silver in the chitosan was 97.8 mg x g(-1).
      Silver was eluted from the chitosan by 1 mol x L(-1) H2SO4. 100 mg x mL(-1) of
      Al3+, Cr3+ and 80 mg x mL(-1) of Ni2+, Cu2+, Pb2+ and Zn2+ did not disturb the
      determination of silver. K+, Na+, Ca2+, Mg2+ and Mn2+ did not disturb the
      determination of silver because they were not adsorbed by chitosan. The method
      has been applied to the determination of silver (1.83 microg x mL(-1)) in waste
      water sample with a recovery of 94.3%.

PMID- 15852881
TI  - [Determination of eight trace elements in the flowers of Hylocereus undatus by
      FAAS].
AB  - The effects of different sample digestives for the flowers of Hylocereus undatus
      are compared. Eight trace elements in the flowers of Hylocereus undatus were
      determined by flame atomic absorption spectrophotometer. The result shows that
      the RSD and recovery are better if the flowers of Hylocereus undatus was digested
      with HNO3-HClO4 (5:1) mixed acid, and the flowers of Hylocereus undatus contains
      many essential elements among which the contents of Fe, Mn and Zn are higher than
      those of Ni and Cu. Co and Cd were not determined, but Pb was determined. The
      experimental results showed that the detection limits were all smaller than 0.086
      microg x mL(-1), the RSDs (n = 8) all smaller than 8.37%, and the addition
      standard recovery (ASR) (n = 8) was 79.69%-118.6% for all elements.

PMID- 15852882
TI  - [Analysis and separation of organic and inorganic speciations of soluble zinc in
      edible flowers].
AB  - Considering the medicinal effects of the edible flowers, the authors studied the
      separation of trace element zinc's soluble organic and inorganic speciations in
      water decoction of three edible flowers: Chrysanthemum, Cottonrose hibiscus and
      Honeysucker by using the 0.45 microm membrane filter and amberlite XAD-2
      macroreticular resins. And trace element zinc contents were determined by atomic
      absorption spectrometry. The optimal conditions for separation had been
      established. This study verifies the economic value of developing edible flowers,
      and provides theoretical basis for developing edible flowers as the third
      functional food materials.

PMID- 15852883
TI  - [Characterization of dinosaur fossils and their surrounding rocks by atomic
      emission spectrometry and X-ray powder diffractometry].
AB  - More dinosaur fossils have been found in the Laochangqing valley, Lufeng county
      than anywhere else in the world, and the dinosaur fossils found here cover the
      longest time span (including the early and middle Jurassic ages). This excavation
      offers an ideal experimental base for prehistoric biology studies. This paper
      presents an elementary analysis of the components and structure of the dinosaur
      fossils in three different geologic-layers and their surrounding rocks in the
      above mentioned area. Atomic emission spectrum shows that the fossils are rich in
      the contents of calcium (>5%) and phosphor, but low in the content of silicon (3%
      8%), while the surrounding rocks are high in the content of silicon (>10%).
      Furthermore, XRD results show that the major compound of the fossils is CaCO3
      (66%), followed by SiO2 (17%); while that of the surrounding rocks is SiO2
      (>80%), followed by CaCO3 (<12%). The most important difference between the
      fossils and the surrounding rocks is, according to the experiment, that phosphate
      has been identified in the former but not in the latter. This is a characteristic
      that can be used to distinguish the dinosaur fossils from other rocks. This paper
      provides valuable data for further zoological studies on the living conditions
      and evolution of the dinosaurs in the Laochangqing valley, Lufeng county.

PMID- 15852884
TI  - [Investigations on the movement of pigment particles in the electrophoretic
      liquids].
AB  - In the present report, the authors studied the movement of pigment particles
      which decide the display status, enduced the equation of the motion and the
      expression of reflectivity, and estimated the value of the delay time. Combining
      the above theoretical conclusion with the experimental results, the authors
      discussed the feasibility of the passive matrix addressing of electrophoretic
      image displays, and provided good advice on how to acquire display devices of
      good quality.

PMID- 15852885
TI  - [Spectral similarity measure and retrieval based on the complete spectral
      reflectance and absorption feature--nonlinear spectral angle mapper].
AB  - A novel method for spectral similarity measure, which is called nonlinear
      spectral angle mapper, is presented. In this method, on one hand, nonlinear
      transformation and removing high relativity among bands are used through kernel
      PCA; on the other hand, the feature of both spectral reflection and absorption
      are combined in transformed space. At last, spectral angle mapper is used to
      measure spectral similarity. The authors' experiments show that this method is
      effective in spectral similarity retrieval.

PMID- 15852886
TI  - [A new method of avoiding entrainment swelling in liquid surfactant membrane for
      the determination of trace Hg(II)].
AB  - Entrainment swelling consists of occlusion swelling and reliquefaction swelling.
      Entrainment swelling is significant to industrialized liquid surfactant membrane
      in the process of operation. The present study based on the life-span of W/O
      emulsion and O/W emulsion discussed the process of forming entrainment swelling.
      The result shows that no matter what surface-active agent was used, the life-span
      of W/O emulsion is 20-88 times longer than that of O/W emulsion. After oil drop
      was dispersed in water, no swelling was discovered, thus, the ratio of swelling
      is less than that by other method. The new method of determination of trace
      mercury by avoiding entrainment swelling in liquid surfactant membrane and FAAS
      is described. The precision(RSD) and recovery are 1.9%-2.3% and 99.8%-101.1%
      respectively. Hg2+ at ng x g(-1) level can be enriched and determined. This
      method can be used in the determination of trace mercury in waste water.

PMID- 15852887
TI  - [Studies on the constituents of polysaccharide and the content of saccharide from
      Mongolian medicine Hara Buri-16].
AB  - This article describes the extraction of dissolvable polysaccharide from Hara
      Buri-16, and using phenyl hydrate-sulfuric acid to determine the content of
      dissolvable polysaccharide. The average recovery is 101.1% and RSD is 0.94%. The
      components of water soluble polysaccharide were identified by gas chromatography
      as: fucose, arabinose, xylose, mannose, galactose and glucose in the molar ratio
      of 0.57:6.67:0.46:6.61:2.47:4.80 respectively.

PMID- 15852888
TI  - [Determination of lead and cadmium contents in chicken granules and gourmet
      powder].
AB  - Through atomic absorption detector, the contents of Pb and Cd in chicken granules
      and gourmet powder were determined. From the result it was found that there are
      differing contents of pollutant elements, i. e. 0.00-10.00 microg x mL(-1) for Pb
      and 0.00-4.00 microg x mL(-1) for Cd, respectively. The relative standard
      deviations of Pb and Cd are 3.15% and 4.26%, respectively. At the same time, a
      recovery experiment for Pb and Cd in chicken granules and gourmet powder were
      performed, and the recoveries are 96.7%-102.1% for Pb and 91.9%-107.6% for Cd,
      respectively.

PMID- 15852889
TI  - Heart failure--definition and diagnosis.

PMID- 15852890
TI  - Insights into the molecular mechanisms of plaque rupture and thrombosis.

PMID- 15852891
TI  - Third heart sound revisited: a correlation with N-terminal pro brain natriuretic
      peptide and echocardiography to detect left ventricular dysfunction.
AB  - BACKGROUND: Auscultation of the third heart sound is an age-old sign for
      predicting ventricular dysfunction. New technology and biomarkers like two
      dimensional echocardiography and N-terminal pro brain natriuretic peptide,
      respectively, have sidelined the utility of this sign, which does not involve any
      cost and is readily accessible. We sought to find the predictive accuracy of
      third heart sound and its correlation with N-terminal pro brain natriuretic
      peptide and ejection fraction using two-dimensional echocardiography to detect
      left ventricular dysfunction in patients of acute coronary syndrome. METHODS AND
      RESULTS: One hundred and ten patients presenting with acute coronary syndrome
      [acute ST elevation myocardial infarction (n=74) and non-ST elevation myocardial
      infarction (n=36)] were prospectively studied. A senior cardiologist, blinded to
      N-terminal pro brain natriuretic peptide and ejection fraction results
      auscultated for a left ventricular third heart sound in each patient. Ejection
      fraction was measured using modified Simpson's technique on two-dimensional
      echocardiography and N-terminal pro brain natriuretic peptide was measured using
      electrochemiluminiscence assay. Median levels of N-terminal pro brain natriuretic
      peptide were used to provide a dichotomous approach for analysis of the data.
      Third heart sound was present in 40 patients (acute ST elevation myocardial
      infarction: n=27, non-ST elevation myocardial infarction: n=13) and absent in 70
      patients (acute ST elevation myocardial infarction: n=47, non-ST elevation
      myocardial infarction: n=23). The sensitivity and specificity of third heart
      sound for predicting N-terminal pro brain natriuretic peptide above median was
      65.5% and 92.7%, respectively. The positive and negative predictive value was 90%
      and 73%, respectively. The N-terminal pro brain natriuretic peptide of those
      having third heart sound was 4081 +/- 2705 pg/ml compared to 1239.3 +/- 1169
      pg/ml in those without third heart sound (p < 0.001). The sensitivity of third
      heart sound to detect ejection fraction <45% was 67.9% while the specificity was
      74.4%. The positive and the negative predictive values were 47.5% and 87.1%,
      respectively. The ejection fraction of patients having third heart sound was 47.5
      +/- 11.3% compared to 56 +/- 10.4% without third heart sound (p < 0.001).
      CONCLUSIONS: Auscultation of third heart sound has a good specificity and
      predictive value for predicting elevated N-terminal pro brain natriuretic peptide
      and left ventricular dysfunction. Thus age-old clinical cardiology still holds
      its forte in this new era of technology-driven cardiology.

PMID- 15852892
TI  - Natural history of secundum atrial septal defect revisited in the era of
      transcatheter closure.
AB  - BACKGROUND: Several reports in the past have described the natural history of
      atrial septal defects, most dealing with a decrease in size or spontaneous
      closure of the defect. Some recent articles have also described an increase in
      size of the defect in a sizable number of cases which may be important in the
      current era of transcatheter closure. We analyzed the data of 52 consecutive
      cases diagnosed to have secundum atrial septal defect in the first year of life,
      seen over the last six years at our center. METHODS AND RESULTS: All infants with
      a defect size of > or =4 mm on echocardiography were included. The first and the
      last echocardiographic images with a minimum interval of 6 months were used for
      analysis. Cases were divided into three groups depending upon the defect diameter
      (small: 4-5 mm, moderate: 6-8 mm and large: > or =9 mm). The age ranged from one
      day to 12 months (mean 2.9 +/- 3.2 months). On a follow-up of 0.7 to 7.0 years
      (mean 2.9 +/- 1.4 years), the septal defect reduced in size in 24 (46%) cases
      with complete closure in 14 of these. The size remained same in 13 (25%) and
      enlarged in 15 (29%) cases. The likelihood of closure was highest in small defect
      group as compared to the large defect group (p < 0.05). Similarly, enlargement
      was more often seen in large defects. CONCLUSIONS: Small atrial septal defects of
      4 mm to 5 mm are very likely to decrease in size or completely close on follow
      up. Larger defects, on the other hand may remain large or enlarge further in a
      significant proportion of cases. A close observation is required for these cases
      if being considered for transcatheter closure.

PMID- 15852893
TI  - Serum leptin levels in acute myocardial infarction.
AB  - BACKGROUND: Several studies have shown an association of serum leptin levels with
      cardiovascular diseases. The present study was undertaken to assess levels of
      serum leptin in patients presenting with acute ST segment elevation myocardial
      infarction. METHODS AND RESULTS: Ninety-four consecutive patients presenting with
      acute ST segment elevation myocardial infarction were studied and 46 controls
      were taken from patients who presented with chest pain but had no history of
      myocardial infarction in the past. There were 59 patients with anterior wall
      infarction and 31 had inferior wall infarction and in 4 it was a combination of
      anterior and inferior wall infarction. The serum leptin levels in patients with
      myocardial infarction was 6.51 +/- 6.76 ng/ml versus 2.86 +/- 2.22 ng/ml in
      controls. In the multivariate analysis the odds ratio for serum leptin with
      myocardial infarction was 1.45 with a 95% confidence interval of 1.2 to 1.8.
      CONCLUSIONS: Our results suggest that serum leptin level is elevated in patients
      with acute ST segment elevation myocardial infarction.

PMID- 15852894
TI  - Post-operative outcome of ventricular reshaping by septal exclusion in patients
      with severe left ventricular dysfunction.
AB  - BACKGROUND: Post-myocardial infarction, anteroseptal dysfunction or akinesia is
      treated by septal reshaping to improve the surgical outcome in patients with
      severe left ventricular dysfunction. METHODS AND RESULTS: Between February 2003
      to December 2003, 30 consecutive patients with previous anterior wall myocardial
      infarction and severe ventricular dysfunction underwent septal reshaping. All the
      dyskinetic and akinetic septal areas were excluded using an oval dacron patch
      which was sutured from the healthy septal area to the anterior wall, resulting in
      formation of a new apex. There were two mortalities in the group. After a mean
      follow-up of 4.2 +/- 1.6 months (1-7 months) it was seen that this procedure
      resulted in significant reduction of ventricular volume, increase in ejection
      fraction, an improvement in New York Heart Association class from 2.9 +/- 1.1 to
      1.7 +/- 0.3, and a better apical geometry. CONCLUSIONS: In selected patients with
      left anterior descending artery occlusion resulting in anteroseptal dyskinesia or
      akinesia, septal exclusion technique provides good clinical and morphological
      results with significant improvement in left ventricular function.

PMID- 15852895
TI  - Conscious off-pump coronary artery bypass surgery.
AB  - BACKGROUND: Cardiothoracic surgery has been previously performed successfully
      under thoracic epidural anesthesia alone. Between October 2001 and December 2003,
      we performed 123 conscious off-pump coronary artery bypass surgeries using
      epidural anesthesia as the sole anesthetic. This technique is an alternative to
      cardiothoracic surgery performed under general anesthesia. Certain modifications
      in the technique facilitate the process. METHODS AND RESULTS: There were 24
      female patients and 99 male patients with mean age of 58.6 +/- 6.2 years; 12
      patients underwent repeat coronary artery bypass surgery. All the patients
      underwent epidural catheterization on the evening before surgery. Out of the 123
      patients scheduled for coronary artery bypass graft surgery, 120 underwent off
      pump coronary artery bypass graft surgery successfully; 4 patients underwent off
      pump surgery via left thoracotomy and the rest through mid sternotomy. These
      patients received 295 grafts in all (single graft in 26 patients, double in 42
      patients, triple in 35 patients, and quadruple in 20 patients). Three patients
      required conversion to general anesthesia and one to cardiopulmonary bypass.
      There was no mortality in the group. CONCLUSIONS: Our experience suggests that by
      modifying the surgical techniques, we can accomplish conscious coronary artery
      bypass surgery.

PMID- 15852896
TI  - Plasma CRP level predicts left ventricular function and exercise capacity in
      patients with acute myocardial infarction.
AB  - BACKGROUND: C-reactive protein estimation can help in predicting short- and long
      term prognosis after acute myocardial infarction. High plasma C-reactive protein
      level in the acute phase strongly indicates a poor clinical outcome of the
      patients with myocardial infarction. METHODS AND RESULTS: One hundred consecutive
      patients admitted with ST elevation myocardial infarction in the intensive
      coronary care unit in our hospital who were able to do symptom-limited treadmill
      test during early recovery phase were studied. Plasma C-reactive protein was
      measured at the time of admission by immunoturbidity method. The normal value of
      the C-reactive protein was taken as 0.8 mg/dl. Echocardiographic study was done
      on day three of admission and ejection fraction was estimated by modified
      Simpson's method. Symptom-limited treadmill exercise test was done in all the
      patients. Patients were classified into two groups based on level of C-reactive
      protein: those with low C-reactive protein level (1.26 +/- 0.91 mg/dl, n=40) and
      those with high C-reactive protein level (6.52 +/- 3.97 mg/dl, n=60). Ejection
      fraction was lower in high C-reactive protein group (46.7 +/- 11.9%) compared to
      low C-reactive protein group (56.9 +/- 7.7%) (p = 0.011). Exercise capacity was
      lower in high C-reactive protein group (2.8 +/- 1.4 METs) compared to low C
      reactive protein group (5.5 +/- 2.5 METs) p = 0.027). CONCLUSIONS: C-reactive
      protein levels are an index of the severity of myocardial necrosis which
      translate to worse left ventricular function. Higher the C-reactive protein
      level, lower the ejection fraction and worse may be the prognosis.

PMID- 15852897
TI  - Non-surgical transpericardial catheter ablation of post-infarction ventricular
      tachycardia.
AB  - Non-surgical transpericardial approach for catheter-based epicardial
      radiofrequency ablation of post-infarction left ventricular tachycardia has been
      described as an alternative and additive procedure to standard endocardial
      technique for delivery of radiofrequency energy in difficult situations. We
      report our initial experience with this approach in three patients of post
      infarction recurrent ventricular tachycardia, refactory to multiple
      antiarrhythmic drugs. Ablation was successful in terminating the tachycardia in
      two and in modifying the circuit to be amenable for control with single
      antiarrhythmic drug in one patient. There were no serious acute or long-term
      complications related to the procedure. Epicardial approach is an effective and
      safe adjunct to standard endocardial ablative technique for patients of post
      infarction ventricular tachycardia.

PMID- 15852898
TI  - Use of PercuSurge in primary angioplasty.
AB  - Thrombus load and its subsequent distal embolization causing slow flow makes
      primary angioplasty a challenging task. Although data is scanty, these
      complications may be potentially mitigated by use of distal protection devices.
      We report 6 cases of PercuSurge distal protection device-assisted primary
      angioplasty. All lesions were stented with patients achieving brisk TIMI 3 flow;
      none of the patients had in-hospital major adverse cardiac events. The strategy
      of PercuSurge Guardwire-assisted primary angioplasty seems encouraging in
      improving successful outcome in this subset of patients.

PMID- 15852899
TI  - Congestive heart failure in unoperated tetralogy of Fallot: can hypoxia be a
      cause?
AB  - A 10-year-old boy with tetralogy of Fallot and congestive heart failure underwent
      a right-sided modified Blalock-Taussig anastomosis because of severe
      biventricular dysfunction and repeated hypercyanotic spells. Postoperatively,
      there was improvement in systemic oxygen saturation and myocardial function. We
      postulate that congestive heart failure occurred because of severe myocardial
      hypoxia and its elimination resulted in markedly improved cardiac performance.

PMID- 15852900
TI  - Seroma following modified Blalock-Taussig shunt resulting in subsequent occlusion
      of the shunt which was opened by balloon angioplasty.
AB  - We report the case of a 9-year-old boy with tetralogy of Fallot who had undergone
      left modified Blalock Taussig shunt. The patient developed seroma around the
      shunt which was excised surgically. The patient developed total occlusion of the
      shunt post-operatively with clinical deterioration. We used emergency
      percutaneous angioplasty to successfully treat the patient.

PMID- 15852901
TI  - Coarctation of aorta presenting as acute abdominal pain.
AB  - Coarctation of aorta is the most common cardiovascular cause of secondary
      hypertension. The condition is correctable although early diagnosis is often not
      made. We report the case of a 9-year-old child who was admitted with severe
      intractable abdominal pain as the presenting symptom of post-subclavian
      coarctation of aorta with hypertension. His pain resolved after control of
      hypertension with parenteral antihypertensives and the narcotic analgesics. He
      subsequently underwent transcatheter balloon dilation of the coarctation of aorta
      and remains well with normal blood pressure on follow-up.

PMID- 15852902
TI  - Ruptured left sinus of valsalva aneurysm to right atrium.
AB  - A 6-year-old child presented with left sinus of Valsalva aneurysm opening in
      right atrium. Origin of sinus of Valsalva from left aortic sinus and its opening
      into right atrium is extremely rare. The anomaly was corrected surgically by
      patch closure at the aortic end. Follow-up echocardiography did not reveal any
      residual shunt in right atrium.

PMID- 15852903
TI  - Thrombolytic therapy for acute ST segment elevation myocardial infarction: should
      it be given to all patients?

PMID- 15852904
TI  - Cobra head deformity of Amplatzer septal occluder.

PMID- 15852905
TI  - Electrocardiographic changes in submassive pulmonary embolism.

PMID- 15852906
TI  - Optimizing intra-aortic balloon timing by pulse oximeter tracing.

PMID- 15852907
TI  - [Sabina przewalskii community structure in the upper reaches of Minjiang River].
AB  - In this paper, the physiognomy and the structure of Sabina przewalskii community
      were studied by sample plot method. The results showed that in the life spectrum
      of the community, hemicryptophyte was dominated, but therophytes also occurred
      frequently, which presented some features of temperate vegetation. The vertical
      structure of the community was quite simple, consisting of tree layer, shrub
      layer and herb layer, and there were no interstratum plants and ground layer.
      Sabina przewalskii was the only species in the tree layer. In fruticose stratum,
      the important value of Spiraea alpina was 153.3, ranking the first; while in herb
      layer, the important value of Carex caespifosa ranked the first, amounting to
      36.8. Among the three plot groups on different slopes, spiny-shrubs such as
      Berberis wilsonae and Caragana erinacea grown on small slope were more than those
      on bigger slope, so did unpalatable grasses such as Pedicularis axillaries and
      Artemisia tauguticat, which mainly owed to retrogressive succession caused by
      frequently grazing. The age and height structures of Sabina przewalskii
      population indicated a declining trend, and the community would develop
      retrogressively if disturbances (e.g., grazing) could not be reduced. The
      disturbance caused by livestock was more obvious in the plot group on small slope
      than on bigger slope, and livestock mainly destroyed seedlings and small trees,
      which made tree population be impossible to regenerate. The coverage of upper
      layers had a notable impact on the lower layers, and there wasn't any correlation
      between coverage and diversity index (Shannon-Wiener Index) in each layer.

PMID- 15852908
TI  - [Relationships between net primary production and nitrogen cycling in Chinese
      forest ecosystems].
AB  - In order to better understand the relationships between net primary production
      (NPP) of forest ecosystem and nitrogen cycling, we studied and analyzed the
      relationships between NPP, litter nitrogen, plant nitrogen retention, and soil
      net nitrogen mineralization rate in Chinese forest ecosystems. The results
      indicated that NPP was linearly and positively related to litter nitrogen, plant
      nitrogen retention and soil net nitrogen mineralization rate, with the most
      correlation with soil net nitrogen mineralization rate (R2 = 0.74, n = 37), and
      the next with plant nitrogen retention (R2 = 0.60, n = 37).

PMID- 15852909
TI  - [Spatial distribution pattern of Larix chinensis population in Taibai Mt].
AB  - Larix chinensis is an endangered species only distributed in Qinling Mountains of
      China. It has a concentrated distribution in Taibai Mt., and plays an important
      role in environmental protection in the high altitude. After an investigation on
      fifteen 400 m2 plots, a comparative study on the spatial distribution pattern of
      L. chinensis population and its dynamics was made by the tests of discrete
      distribution pattern and aggregation intensity. The results showed that at
      different sampling areas, L. chinensis populations all performed the pattern of
      clustering distribution. As the sampling area increased, the congregating
      intensity of L. chinensis population appeared the pattern of high-->low-->high,
      but the highest congregation occurred in the areas of 100 m2 and 25 m2. The
      clustering intensity went down from low to high altitude, and the area with the
      highest clustering intensity occurred on that of 25 m2 in low altitude, 150 m2 in
      middle altitude, and 100 m2 in higher altitude. The clustering intensity in shade
      slope was higher than that in sunny slope, and the area with the highest
      clustering intensity was 100 m2 on shade slope, and 150 m2 on sunny slope. With
      the population age increased, the distribution pattern had a trend from
      clustering to random, the clustering intensity decreased somewhat, and the area
      with the highest clustering intensity was 150 m2 in young or old stages, and 100
      m2 in middle stage. The distribution pattern of L. chinensis population was
      related to its ecological characteristics, community composition, and
      environmental factors. In situ conservation should be strengthened in the future.
      In lower altitude or on shade slope, the measurements of thinning no-aim in tree
      and shrub species should be taken; while in higher altitude area or sunny slope,
      thinning shrub species in patch form would be better for L. chinensis populations
      block renovating. The fostering area for L. chinensis populations should be suit
      to the area with the highest clustering intensity of populations.

PMID- 15852910
TI  - [Alleviation effect of exogenous Ca, P and N on the growth of Chinese fir
      seedlings under Al stress].
AB  - In this study, three month-old seedlings of Chinese fir (Cunninghamia laceolata)
      were grown in solution culture with 1 mmol x L(-1) Al at pH 4.0 for 80 days to
      evaluate the effects of varying concentrations of Ca, P, and NH4+-N or NO3(-)-N
      in solution on their growth. The morphological indexes (fresh weight, dry weight,
      shoot length, root length and relative elongation ratio) and physiological
      indexes (MDA content and POD activity) were submitted to statistical analysis and
      compared. The results indicated that the seedlings weight or shoot length had a
      significantly positive correlation with the molar ratio of solution Ca/Al. The
      MDA content and POD activity decreased with the increasing molar ratio of Ca/Al,
      and Ca/Al > or = 2.8 was the critical ratio. Similar to Ca/Al, high P/Al molar
      ratio also had an obvious effect on the growth of Chinese fir seedlings under Al
      stress, and P/Al > or = 4.5 was the critical ratio. The growth of Chinese fir
      seedlings was improved by increased NH4+-N supply, but the effect was less
      obvious than Ca and P. Solution NH4+-N/Al > or = 4.7 was the critical molar
      ratio. Solution NO3(-)-N could mitigate some adverse effects of Al on Chinese fir
      seedlings growth, but no regular effects were found with the change of solution
      NO3(-)-N/Al molar ratio.

PMID- 15852911
TI  - [Effects of exogenous nitric oxide on photosynthetic characteristics of poplar
      leaves under water stress].
AB  - Nitric oxide (NO) is an active molecule involved in many biological pathways, but
      its effects on photosynthesis of tree leaves have not been established yet. This
      paper studied the effects of exogenous NO, sodium nitroprusside (SNP), on the
      water status, photosynthesis and scavenging enzyme activities in poplar leaves.
      Different levels of SNP treatments had remarkable effects on the water content of
      leaves, which increased with increasing SNP levels. When the SNP level exceeded
      500 micromol x L(-1), differences in leaf water content were no longer
      significant between different SNP treatments. Exogenous NO increased the
      photosynthesis rate, photochemical efficiency of PSII Fv/Fm, and Fm/Fo and Fv/Fo
      ratios, and the effects decreased with increasing duration of water stress. The
      SOD and POD activities in poplar leaves were higher in 1 hour water stress
      treatment than in 3 h treatment. Treating with SNP could markedly increase POD
      activity, but SOD activity did not change much. POD and SOD activities increased
      initially, and then decreased with increasing SNP levels. The results indicated
      that exogenous NO delayed the accumulation of active oxygen by increasing POD and
      SOD activities, and thereby, alleviated the effects of water stress on
      photosynthetic organization of poplar leaves.

PMID- 15852912
TI  - [Relationship between plant community succession and fertility variation of
      mountain yellow soil in east Chongqing].
AB  - Based on the analyses of soil physical and chemical properties, this paper
      studied the relationship between plant community succession and fertility
      variation of mountain yellow soil in east Chongqing. The results showed that the
      values of integrated soil fertility index of Pinus massoniana, Cunninghamia
      lanceolata, deciduous oak, Camellia sinensis and evergreen broad-leaved forest
      soils were 0.1256, 0.2085, 0.3514, 0.2479 and 0.9329, respectively, implying that
      soil development had a close relation to plant community succession.

PMID- 15852913
TI  - [Spatial distribution pattern and fractal analysis of Larix chinensis populations
      in Qinling Mountain].
AB  - In this paper, the fractal characters of Larix chinensis populations in Qinling
      Mountain were studied by contiguous grid quadrate sampling method and by boxing
      counting dimension and information dimension. The results showed that the high
      boxing-counting dimension (1.8087) and information dimension (1.7931) reflected a
      higher spatial occupational degree of L. chinensis populations. Judged by the
      dispersal index and Morisita's pattern index, L. chinensis populations clumped at
      three different age stages (0-25, 25-50 and over 50 years). From Greig-Smiths'
      mean variance analysis, the figure of pattern scale showed that L. chinensis
      populations clumped in 128 m2 and 512 m2, and the different age groups clumped in
      different scales. The pattern intensities decreased with increasing age, and
      tended to reduce with increasing area when detected by Kershaw's PI index. The
      spatial pattern characters of L. chinensis populations may be their responses to
      environmental factors.

PMID- 15852914
TI  - [Experience model for self-thinning process of even-aged pure stands].
AB  - Based on the famous -3/2 power rule and generalized Schumacher growth equation, a
      mathematical model for the density change of even-aged pure stands with time
      during self-thinning process was presented, and the genetic algorithms was used
      to fit this nonlinear model. With the collected data from Populus tremula var.
      davidiana, Pinus yunnanensis and Cunninghamia lanceolata even-aged pure stands,
      the new model was verified and compared with other models. The results showed
      that the new model could fit observed data very well, and was very useful in
      practice. The surplus square, mean relative error, mean absolute error and
      surplus standard deviation of the new model were all smaller than those of other
      models, indicating its good qualification in describing stand density change
      during self-thinning process and its useness in studying forest self-thinning
      rules. The study also showed that genetic algorithms could give a better global
      convergence, and be used to estimate the parameters of nonlinear models in
      ecology, biology and forestry.

PMID- 15852916
TI  - [Simulation of nitrogen mineralization and immobilization of crop straw during
      its initial decomposition in soil].
AB  - The nitrogen (N) transformation of crop straw during its initial decomposition in
      soil was simulated by Model-maker software. A good fit was obtained between the
      simulated and measured data of 6 variables, including the amount of soil ammonium
      N, nitrate N, microbial biomass N and their 15N atom %. The simulation results
      indicated that the main N form immobilized by soil microbes was ammonium, while
      the immobilization of nitrate was very small. N mineralization occurred
      dominantly in crop straw but very small in humus. The N mineralization of crop
      straw could be better described by first order than zero order kinetics. N re
      mineralization occurred later than N immobilization. The assumptions on the
      absence of N re-mineralization or the simultaneous presence of re-mineralization
      and immobilization during straw decomposition led to a serious error in
      calculating the gross N mineralization and immobilization; while no consideration
      of nitrification and volatilization losses led to a low estimation of gross N
      mineralization. The occurrence of net N mineralization or net N immobilization
      depended not only on the C/N of straw, but also on the duration of straw
      decomposition.

PMID- 15852915
TI  - [Effects of urease and nitrification inhibitors on alleviating the oxidation and
      leaching of soil urea's hydrolyzed product ammonium].
AB  - With simulation test of in-situ soil column, this paper studied the effects of
      urease inhibitor hydroquinone (HQ), nitrification inhibitors coated calcium
      carbide (ECC) and dicyandiamide (DCD),and their different combinations on the
      persistence, oxidation, and leaching of soil urea's hydrolyzed product ammonium.
      The results showed that compared with other treatments, the combination of HQ and
      DCD could effectively inhibit the oxidation of the ammonium, and make it as
      exchangeable form reserve in soil in a larger amount and a longer period. The
      inhibition of this oxidation not only decreased the accumulation of oxidized
      product NO3- in soil, but also decreased the potential of NO3- leaching, making
      the NO3- only leach to 5-10 cm in depth, and the leached amount significantly
      decreased.

PMID- 15852917
TI  - [Short-term changes of pH value and Al activity in acid soils after urea
      fertilization].
AB  - Acidic soils are widely distributed in South China, and their acidity is the
      major environmental stress factor limiting the growth of most crops. It is well
      known that soil Al solubilized at low pH is a main toxic factor for plant growth.
      Our study with three acidic soils showed that soil pH increased quickly, while
      soil exchangeable Al decreased sharply with the increasing concentrations of
      applied urea. The time-course experiment revealed that the increase of soil pH
      was short-lived, with a subsequently slow drop after reached its maximum. Urea
      fertilization caused a drastic change of soil pH during 2-4 weeks of the
      experimental period. There was a negative relationship between soil pH and soil
      exchangeable Al. Biological toxicity test demonstrated that applying urea to
      acidic soils could obviously decrease the aluminum toxicity of maize in a short
      term period.

PMID- 15852918
TI  - [Effects of fertilization on soil active organic carbon under Phyllostachys
      praecox stand].
AB  - In this paper, fertilization experiment was conducted on Phyllostachys praecox
      stand to study the effects of different heavy application of chemical fertilizers
      and manure on soil active organic carbon pool. The results showed that compared
      with only applying chemical fertilizers, the combined application of chemical
      fertilizers and manure significantly increased the contents of soil total organic
      carbon (TOC), water-soluble organic carbon (WSOC), microbial biomass carbon (MBC)
      and mineralized carbon (MC) as well as the ratios of WSOC/TOC, MGC/TOC and MC/TOC
      (P < 0.01 or P < 0.05). With the decreasing application rate of manure, soil TOC,
      WSOC, MBC and MBC/TOC decreased significantly (P < 0.05), and when the
      application rate of manure was decreased by 50%, soil TOC, WSOC, MBC and MBC/TOC
      decreased by 10.75%, 12.02%, 30.94% and 22.61%, respectively. In the treatments
      of only applying chemical fertilizers, soil WSOC, MBC and MBC/TOC decreased
      obviously when the application rate of fertilizer nitrogen exceeded 1009.5 kg x
      hm(-2) x yr(-1). There were significant correlations between soil TOC, WSOC, MBC
      and MC (P < 0.01 or P < 0.05), among which, MBC and MBC/TOC could be used as the
      quality indications of soil carbon pool under Phyllostachys praecox stand.

PMID- 15852919
TI  - [Several infection factors of Pseudoperonospora cubensis].
AB  - The study on the effects of temperature and humidity on the pathogenicity of
      Pseudoperonospora cubensis showed that the optimum temperature for the occurrence
      of cucumber downy mildew was 25-35 degrees C. An alternation of 15/35 degrees C
      was the most propitious to the infection of Pseudoperonospora cubensis, while the
      high temperature above 35 degrees C could kill the pathogens. 2 hours humid was
      enough for infection. Pseudoperonospora cubensis stored at -20 degrees C for 10
      months and dried for 7 days could still infect cucumber. The infected cucumber
      leaves could continuously produce sporangium, with its quantity gradually
      decreased with time. The quantity of sporangium produced in vivo was more than
      that in vitro.

PMID- 15852920
TI  - [Productivity of crop-fruit ecological agriculture in middle-south Loess
      Plateau].
AB  - With the Xipo, Feimahe and Nangou villages as test objects, the productive
      characteristics of crop-fruit ecological agriculture in the middle-south Loess
      Plateau were investigated. The results showed that the biomass productivity of a
      plant was different with its organs, the highest for grain or fruit, and followed
      by stem, leaf and root. In the crop-fruit ecological agriculture, the higher
      ratio the crop subsystem, the higher productivity its biomass, the lower economic
      productivity and lower economic value was; while the fruit subsystem was on the
      contrary. The productivity of livestock farming subsystem was in a lower level,
      which restricted the increase of the total ecosystem's productivity. Based on
      these results, a countermeasure of increasing the ecosystem productivity was put
      forward.

PMID- 15852921
TI  - [Effects of exogenous Ca on some physiological characteristics of tomato
      (Lycopersicon esculentum) seedlings with different Ca sensitivity].
AB  - Two tomato (Lycopersicon esculentum) cultivars with different Ca sensitivity were
      used to study the effects of exogenous Ca on their root activity, CaM content,
      chlorophyll a/b ratio, and reactive oxygen-scavenging enzymes' activities under
      different Ca concentrations in nutrient solution. The results showed that the
      root activity and CaM content of two cultivars increased with increasing Ca
      concentrations in the nutrient solution. The root activity and chlorophyll a/b
      ratio of Ca-insensitive cultivar Jiangshuyihao were higher than those of Ca
      sensitive L-402 under extreme low Ca stress (1 and 4 mg x L(-1)), while lower
      than those of L-402 when sufficient Ca was applied (100 mg x L(-1)), indicating
      that Jiangshuyihao had a greater capability to bear the nutrient and light stress
      under low Ca stress. The SOD activity of Ca-insensitive cultivar Jiangshuyihao
      under 1 and 4 mg x L(-1) Ca was higher than that of L-402, while the activities
      of POD and CAT of L-402 were consistently higher than that of Jiangshuyihao under
      test Ca concentrations in the nutrient solution. Comparing with 100 mg x L(-1) Ca
      in solution, 4 mg x L(-1) Ca led to an increase of CAT and POD activities and a
      decrease of SOD activity in the two cultivars, but the variation of SOD activity
      was greater in L-402 than in Jiangshuyihao, indicating that the system of defence
      enzymes in Ca-insensitive cultivar played a key role when suffered from Ca
      stress.

PMID- 15852922
TI  - [Physiological characteristics of nitrogen nutrition and stress-resistance of
      film-mulched rice in various ecological regions of Zhejiang Province].
AB  - The study showed that different ecological environment and cultivation system in
      various ecological regions of Zhejiang Province resulted in some different
      physiological characteristics of nitrogen nutrition and stress-resistance,
      especially in the aspect of NO3(-)-N and NH4+-N concentrations, between film
      mulched and conventional flooded rice. Owing to the heat stress in Hangjiahu
      plain, the NO3(-)-N concentration of film-mulched rice decreased to some extent,
      but NH4+-N concentration increased markedly at tillering, jointing and booting
      stages, compared to conventional flooded rice. In Jinqu basin, the NO3(-)-N
      concentration of film-mulched rice at booting stage was higher, while the NH4+-N
      concentration in its roots was notably lower than those of conventional flooded
      rice, with NH4+-N concentration in its basal stems and leaves somewhat increased.
      Generally, the glutamine synthetase (GS) and nitrate reductase (NR) activities in
      film-mulched rice leaves were enhanced at booting stage, while malondiadehyde
      (MDA), soluble sugar (SS) and proline (Pro) concentrations had little changes. In
      conclusion, film-mulched cultivation was beneficial to the rice growth and its
      high yielding.

PMID- 15852923
TI  - [Gradient distribution of soil nitrogen and its response to climate change along
      the Northeast China Transect].
AB  - Terrestrial transect is an important and effective method for global change
      study. The Northeast China Transect (NECT), which is assigned along the latitude
      43 degrees 30'N in the mid-latitude of temperate zone and located at 112 degrees
      130 degrees 30'E and 42-46 degrees N, is one of the fifteen global transects
      recognized by IGBP. It is about 1600 km in length and 300 km in width. The NECT
      is mainly driven by precipitation, and becomes an effective platform of global
      change study in China. Based on the field survey in 2001 and a simulated
      experiment, this paper analyzed the gradient distribution of soil nitrogen and
      its response to climate change along the Transect. The results indicated that
      soil total and available nitrogen in NECT were significantly related to
      longitude, with a correlation coefficient being 0.695 (P < 0.001) and 0. 636 (P <
      0.001), respectively, and had a similar horizontal distribution with soil organic
      carbon. Soil available nitrogen content in the NECT was decreased from east to
      west, and could be one of factors restricting plant growth. The decreasing rate
      of soil total and available nitrogen from topsoil to subsoil was different with
      ecosystems along the NECT. Soil total and available nitrogen contents had a close
      linear relationship with soil pH, total and labile carbon, total and available
      phosphorus, total sulphur, total and available zinc, available potassium,
      available manganese, bulk density, water holding capacity, and total porosity.
      They also had a significant linear relationship with precipitation, the
      correlation coefficient being 0.682 (P < 0.001) and 0.688 (P < 0.001),
      respectively. The short-term simulated experiment showed that doubled ambient CO2
      concentration and soil moisture regime had no significant effects on soil total
      and available nitrogen, the variation coefficients being 5.55% and 3.84%,
      respectively.

PMID- 15852924
TI  - [Wave-type time series variation of the correlation between NDVI and climatic
      factors].
AB  - Based on the 1992-1996 data of 1 km monthly NDVI and those of the monthly
      precipitation and mean temperature collected by 400 standard meteorological
      stations in China, this paper analyzed the temporal and spatial dynamic changes
      of the correlation between NDVI and climatic factors in different climate
      districts of this country. The results showed that there was a significant
      correlation between monthly precipitations and NDVI. The wave-type time series
      model could simulate well the temporal dynamic changes of the correlation between
      NDVI and climatic factors, and the simulated results of the correlation between
      NDVI and precipitation was better than that between NDVI and temperature. The
      correlation coefficients (R2) were 0.91 and 0.86, respectively for the whole
      country.

PMID- 15852925
TI  - [Fragmentation process of wetland landscape in watersheds of Sanjiang Plain,
      China].
AB  - The Sanjiang Plain is the largest fresh water wetland distribution area in China
      and the center of waterfowls breeding and habitat area in Asia, but over the past
      50 years, more than 73% of its wetland had lost because of agricultural
      development, and as a result, the wetland biodiversity declines dramatically, and
      the remnant wetlands are in a very fragment state. Based on historical maps,
      remote sensing data and GIS techniques, this paper selected two watersheds to
      analyze their wetland landscape fragmentation process during 1950-2000. It was
      indicated that land reclamation resulted in a decrease of 98% wetland corridors
      in Qixing River, 90% in Naoli River, 87% in the middle reach of Bielahong River,
      and 94% in the lower reach of Bielahong River; The amount of isolated wetlands in
      watershed increased dramatically; The maximum patch areas of wetland decreased by
      92.6% in Naoli River watershed and 74.6% in Bielahong River watershed, and the
      mean wetland patch area in the two watersheds decreased by 99%. Before 1983, the
      wetland landscape was in an extensive area distribution state (the index of patch
      density was < 0.1), but after 1983, it fragmented dramatically, with the index of
      patch density larger than 1.5. The shape fragmentation indices of wetland
      decreased from 1950 to 2000, indicating a very big change in wetland patch shapes
      in the watersheds. The area fragmentation indices of wetland also increased from
      1950 to 2000, especially after 1983, showing that the wetlands were in a serious
      fragmentation state. The wetland landscape fragmentation changed from a landmass
      and island model to a satellite model, and finally to a completely isolated
      model, which indicated the great changes in spatial structure of wetland in the
      Sanjiang Plain.

PMID- 15852926
TI  - [Land cover classification in Xianghai Nature Reserve].
AB  - This paper discussed the application of Fuzzy ARTMAP neural network in land cover
      classification in Xianghai Nature Reserve. The structure and algorithm of Fuzzy
      ARTMAP neural network were described in detail, and an automatic adjustment
      method of vigilance parameter was put forward to solve the problem of searching
      the optimum value in the selection of vigilance parameter. The results showed
      that the automatic adjustment method could adjust network parameter
      automatically, and improve the running speed of network. In comparing with
      maximum likelihood classification method and traditional Fuzzy ARTMAP neural
      network, the Fuzzy ARTMAP neural network with the functioning of automatic
      adjustment depended less on samples and had higher accuracy, and thus, could
      effectively make the classification of TM image covering Xianghai Nature Reserve.
      It's shown from the classification that in the Xianghai Nature Reserve, farmland
      covered large area while grassland and marsh were facing degradation, and hence,
      corresponding countermeasures should be taken to improve the eco-environment of
      this Reserve.

PMID- 15852927
TI  - [Structural characteristics and heterogeneity analysis of yard-greenbelts in
      Shenyang city].
AB  - The analysis of the landscape and pattern of yard-greenbelts in Shenyang city
      indicated that residential greenbelt had the highest green path number, occupying
      32.2% of all greenbelt types, but the virescence situation in residential area
      was the worst because its greenbelt ratio was only 19.5% in average. The average
      area of all yards was 4.04 hm2, with an average greenbelt of 0.93 hm2, and the
      green belt ratio was 23% in average that was lower than the standard established
      by the government. About 62.7% of all yards were lower than 15% in virescence,
      and 30% of them had a < 13.3% of virescence. Micro-green patch was dominant (over
      70%) in Shenyang yard-greenbelts. Landscape diversity index of residential areas
      was the highest, while that of hospital and army units was the lowest. The
      dominant degrees of all yard-greenbelt types in the researched 7 districts of the
      city were obviously different. The dominance of factory greenbelt in Yuhong
      district was 31.23 times of that in Heping district. The evenness indexes were
      also very different, the highest in residential greenbelt and the lowest in army
      unit. The highest fragmentation degree was in residential greenbelt and the
      lowest in army unit. The fragmentation degrees of old districts, especially in
      Shenhe district were more serious than the new districts.

PMID- 15852928
TI  - [Characteristics, dynamics and niche of insect community in plum orchard].
AB  - The insect community in plum orchard was investigated on organization level and
      temporal-spatial niche. The results showed that the insect community was
      abundant, which included 6 orders, 23 families. The individuals of species,
      diversity indices, and evenness increased with time. Myzus persicae and
      Asiaarposina sasokii had the widest spatial niche breadth, while Didesmococcus
      koreauus borchs had the widest temporal niche breadth. Among the natural enemies,
      Chilocorus rubidus had the widest both temporal and spatial niche breadth. The
      niche of Chicocorus rubidus and Didesmococcus koreauus overlapped larger than
      that of the others, which indicated their synchrony in temporal dimension and
      their similarity in spatial dimension. As the dominant natural enemies, the two
      populations should be protected and utilized to control plum pest.

PMID- 15852929
TI  - [Suppressive effects of non-preferable plant alcohol extracts on diamondback moth
      Plutella xylostella population].
AB  - In this paper, a life table and an interference index of population control
      (IIPC) were used to evaluate the effects of spraying the alcohol extracts of non
      preferable plants on the dynamics of diamondback moth Plutella xylostella)
      population. The results showed that the alcohol extracts of Eupatorium odoratum,
      Lantana camara and Wedelia chinensis were available to protect kidney bean from
      Plutella xylostella infestation. Their IIPC were 0.110, 0.136 and 0.165, and the
      efficacies of controlling P. xylostella were 89.0%, 86.4% and 83.5%,
      respectively, compared with control.

PMID- 15852930
TI  - [Scanning electron microscopic observations of Monochamus alternatus antennal
      sensilla and their electroantennographic responses].
AB  - With scanning electron microscope (SEM), this paper observed the shape, category,
      amount and distribution of the main antenna sensilla of adult Monochamus
      alternatus, and tested their electroantennographic (EAG) responses to the main
      volatiles of Pinus spp.. There were seven types of antennal sensilla, i. e.,
      sensilla trichoid, sensilla basiconica, sensilla digit-like, sensilla rod-like,
      sensilla bottle-like, sensilla bud-like and sensilla chaetica, among which,
      sensilla trichoid and sensilla basiconica were the most abundant on the antenna
      surface, and each of them could be divided into three subtypes. Two subtypes of
      sensilla digit-like could also be observed. The II and III subtypes of sensilla
      trichoid and I and II subtypes of sensilla basiconica had deep longitudinal
      grooves on their surface, the typical characteristics of olfactory receptor. The
      comparison of the EAG response of different parts of Monochamus alternatus
      antennae to alpha-Pinene showed that each volatile and their compounds could
      provoke significant EAG responses of both females and males. The dose-response
      test showed that there was a certain rule in the EAG responses of M. alternatus.

PMID- 15852931
TI  - [Selection behavior of Cuscuta japonica on their hosts].
AB  - A field investigation on the selection behavior of Cuscuta japonica on their
      hosts showed that among the test plant communities, the number of coiling, the
      time of haustorium occurring, and the rate of coiling of C. japonica on hosts
      followed the order of B. papyrifera, W. chinensis, I. cairica, and L. camara; but
      the length of the elongation of C. japonica growing tips from coiling to
      haustorium occurring was with the order of L. camara, I. cairica, W. chinensis,
      and B. papyrifera. Furthermore, the growing tips of C. japonica coiled 3 circles
      in left direction on all selected hosts in 12 hrs, but grew away after contacting
      PVC rods within 24 hrs. The host diversity of C. japonic was beneficial to the
      survival of both C. japonica and its hosts. The selection behavior of C. japonica
      on their hosts had no correlation with the total N contents of different hosts.
      It could be postulated that the secondary metabolites of hosts made a
      contribution to the selection behavior of C. japonica on their hosts.

PMID- 15852932
TI  - [Cu and Zn pollution and soil enzyme activities in sewage irrigation area near
      smeltery].
AB  - This paper studied the Cu and Zn status in soil and rice plant as well as the
      soil enzyme activities in the sewage irrigation area near a smeltery. The results
      showed that the soils near the smeltery were polluted. The soil total and
      extractable Cu contents at the distance of 100 m were 182.45 and 81.91 mg x kg(
      1), respectively, 9.3 and 34 times higher than the control. The Cu concentration
      in different parts of rice was in order of root > leaf and stem > grain, while
      the Zn concentration was in order of leaf and stem > root > grain. Zn was more
      mobile than Cu which was likely to accumulate in rice root. It was considered
      that root could act as a barrier which retarded the upwards transport of Cu and
      protected the above ground parts of rice from toxication. The Cu contents of rice
      stem and leaf had a significant correlation with soil Cu contents in the sewage
      irrigation area. Among the three test enzymes, urease was the most sensitive one
      to Cu, and its activity had a significant correlation with soil Cu content.
      Therefore, it is feasible to use soil urease activity as an indicator of soil Cu
      pollution in sewage irrigation area near the smeltery.

PMID- 15852933
TI  - [Effects of acid rain on nitrogen content in the water body of Wenzhou Sanyang
      wetland].
AB  - In order to understand the effects of acid rain on the nitrogen (N) content in
      the water body of Wenzhou Sanyang wetland, this paper measured the concentrations
      of different N forms in the wetland, of which, NH4+-N was 2.90-10.75 mg x L(-1),
      average in 5.38 mg x L(-1); NO3(-)-N was 0.16-0.44 mg x L(-1), average in 0.31 mg
      x L(-1); and total was 34.04-63.20 mg x L(-1), average in 55.75 mg x L(-1). The
      pH value was 6.1-6.5, average in 6.4. The measurement of the N input from
      precipitation in the past two years and its proportion to the existed N in the
      water body of the wetland showed that the input of NH4+-N, NO3(-)-N and total N
      was 2.48 x 10(4)-2.86 x 10(4) kg, 2.87-4.96 x 10(4) kg and 5.35 x 10(4)-7.82 x
      10(4) kg, and its proportion was 56-64%, 11.21-19.38 times and 12%-17%,
      respectively. The N amount directly to the wetland water body was 0.72 x 10(4)
      0.84 x 10(4) kg, 0.83 x 10(4)-1.44 x 10(4) kg and 1.55 x 10(4)-2.27 x 10(4), and
      its proportion was 16%-19%, 3.24-5.63 times and 3%-5%. The results indicated that
      acid rain was one of the main sources of pollutant nitrogen which aggravated the
      water pollution of the Sanyang wetland.

PMID- 15852934
TI  - [Physiological responses of Ceratophyllum demersum under different nutritional
      conditions].
AB  - With static experiments, this paper investigated the protein and chlorophyll
      contents, and the peroxidase (POD) and superoxide dismutase (SOD) activities of
      Ceratophyllum demersum cultured in meso-, eutro- and hypertrophic and Hoagland's
      solutions. The results showed that the changes of total N (TN) and total P (TP)
      concentrations in nutrient solutions had an obvious effect on the biosynthesis of
      C. demersum. When the concentrations of TN and TP were less than 1 mg x L(-1) and
      0.1 mg x L(-1), respectively, the protein and chlorophyll contents of plant
      declined. The plant from eutrophic solution had higher SOD and POD activities. It
      was indicated that C. demersum was more preferable to eutropic condition (1 mg TN
      x L(-1) and 0.1 mg TP x L(-1)), and the raised concentration of nutrients (e. g.,
      hypertrophic and Hoagland's solutions) was a stress to C. demersum and could
      affect its hardiness physiology.

PMID- 15852935
TI  - [Effects of Dipterocarpaceae on arbuscular mycorrhizal fungi].
AB  - An investigation was carried out on the colonization percentage, spore density,
      relative abundance, occurrence frequency, and species richness of arbuscular
      mycorrhizal (AM) fungi on 4 species of Dipterocarpaceae trees grown both in
      natural forests in Yunnan and Hainan Provinces and in greenhouse pots. The
      results showed that all dipterocarp species were able to form AM, the
      colonization rates ranged from 30.6% to 45.3%, 37% on average. Hopea hainanensis
      (Dipterocarpacea) seedlings without AM fungal colonization were cultivated in
      pots with soil collected from Dipterocarpacea rhizosphere, and harvested a year
      later. The colonization rate of the seedlings ranged from 10.6% to 20.3%, 14.2%
      on average, indicating the significant effect of host plants on AM fungi
      frequency. The relative abundance of Glomu, Acaulospora and Gigaspora also varied
      with host plants. It was concluded that the dominant AM fungi in the rhizospheric
      soil of dipterocarp plants were Acaulospora spp. and Glomus spp. Using the same
      species of Dipterocarpacea as host plants might promote the growth and
      development of AM fungi, and increase the AM diversity.

PMID- 15852936
TI  - [A comprehensive quantitative assessment model for arid area's basin water-soil
      environment quality].
AB  - The existing assessment models for water-soil environment quality are usually
      established on the relationships between assessment indicators and their
      assessment criteria. Such kinds of models are varied with regional scale, and
      always need a mass of calculation work. This paper tried to find a general
      assessment model based on a given water-soil quality assessment criteria. In this
      process, stochastic technology was used to simulate enough assessment indictor
      series, and then, assessment model was built up by using artificial neural
      network to assess these series. This model could reduce work load, and needn't
      construct functional relations between assessment indicators and their criteria
      and calculate weigh value. A case study in a basin with the highest level of
      water resources utilization showed that the model was practical and convenient,
      and could be used in basin water-soil quality assessment.

PMID- 15852937
TI  - [Correlation analysis on the damage of Mikania micrantha to plant communities in
      Neilingdind Island of Guandong Province, China].
AB  - The analysis showed that 58 species of trees, short-trees and shrubs in
      Neilingding Island of Guangdong Province were damaged by M. micrantha, of which,
      woody trees accounted for 67%. Short-trees and sunny shrubs were damaged most
      seriously, followed by the communities with low canopy density consisted of only
      2 dominant species, and those with high canopy density consisted of 5 or 6
      dominant species. The coverage of M. micrantha mainly related to the vertical
      structure of plant communities. The taller the community height and the more the
      synusia, the lesser was the coverage of M. micrantha. The damaging ratio mainly
      related to species diversity and community density. The higher the species
      diversity and community density, the lower the damaging ratio was. The damaging
      degree mainly related to the coverage of other liana. The more the coverage of
      other liana, the higher was the damaging degree of M. micrantha.

PMID- 15852938
TI  - [Effects of ecological environment in Qinba Mountains on hair trace element
      contents of local inhabitants].
AB  - Determinations of Zn, Fe, Ca, Cu, Mg, Al, Se, Mn, Cr and Pb contents in the hairs
      of 136 children aged 0-13 and of 22 adults in the Qinba Mountains showed that the
      contents of test trace elements except Mg were abnormal in different degrees. The
      Al, Mn and Cr contents were highly excessive, their mean values being 2.04, 1.67
      and 2.07 times as the highest value of normal range, and the people excessive in
      three elements occupied 83.54%, 77.85% and 72.78%, respectively. On the other
      hand, Zn and Se contents were in shortage, with the mean values being only 91.96%
      and 68.33% of the lowest value of normal range, and the people deficient in Zn
      and Se occupied 69.62% and 79.11%, respectively. Based on the local environmental
      geochemistry, this paper analyzed the possible causes of this abnormal status in
      trace elements and its harm.

PMID- 15852939
TI  - [Ecological restoration and reconstruction of degraded lakeside zone ecosystem].
AB  - As a kind of aquatic-terrestrial ecotone, lakeside zone plays an important role
      in the lake basin ecosystem, and has high ecological, social and economic values.
      Its functions include lake buffer, conservation of biological diversities and
      special habitats, dike protection from soil erosion, and economic and esthetics
      values. The main factors inducing lakeside zone degradation are the anthropogenic
      activities that caused the converse succession of communities and the decline of
      ecological function. The theoretical basis of ecological restoration and
      reconstruction of degraded lakeside zone is restoration ecology; while the
      technologies are of three types, i. e., habitat restoration and reconstruction,
      species restoration and reconstruction, and structural and functional
      restoration. A three-year case study on the ecosystem restoration and
      recontruction of degraded lakeside zone of Erhai Lake in Yunnan Province showed
      that the aquatic macrophytes were restored, purifying function was distinct,
      algae were restrained, and the component and individuals of zooplankton were
      changed. In a word, the biological diversity and stability in the degraded
      lakeside-zone ecosystem increased after the restoration and reconstruction.

PMID- 15852940
TI  - [Research advance in response of forest seedling regeneration to light
      environmental heterogeneity].
AB  - Based on the analysis of characteristics of forest light environmental
      heterogeneity, this paper reviewed the research advance in the response of forest
      seedlings to light environmental heterogeneity from the aspects of
      photosynthesis, thermal dissipation, biomass accumulation and distribution,
      morphological traits, germination, and population dynamics, and discussed the
      ecological significance of different responses of seedling regeneration to light
      environmental heterogeneity in forest biodiversity maintenance, forest
      succession, and revegetation. Some suggestions for future research in this field
      were put forward.

PMID- 15852941
TI  - [Research advances in catalytic kinetics of soil oxidoreductase].
AB  - Soil oxidoreductase is a group of enzymes catalyzing many important soil
      biochemical reactions and concerning with the transformation of soil organic
      matter, formation of humic substance, and dynamics of soil fertility. The
      catalytic kinetics of oxidoreductase can illuminate its catalytic
      characteristics, substantial properties, and response to environmental changes.
      This paper summarized the research advance of its kinetics, and proposed some
      comments in understanding its action mechanism and in regulating its catalytic
      processes.

PMID- 15852942
TI  - [Redundancy theory and its application in agro-ecosystem management].
AB  - Redundancy theory is an ecological theory developed in 1990s. This paper gave a
      brief introduction on the concept of redundancy, its hypothesis and redundancy
      degree, and briefly reviewed the research advances in redundancy theory and in
      the methodologies about species redundancy, layer redundancy, gene redundancy,
      and growth redundancy. A hypothesis of optimal growth redundancy degree (OGRD)
      was proposed, i. e., under certain cultivation and management conditions, there
      existed a growth redundancy degree corresponding to the highest crop yield, and a
      high yield would be obtained if OGRD could be achieved through the regulation of
      management practices. The hypothesis was tested by using the data from high
      yielding rice cultivation cases.

PMID- 15852943
TI  - [Research advance on environmental exposure and ecotoxicological effects of
      polybrominated diphenyl ethers (PBDEs)].
AB  - Polybrominated diphenyl ethers (PBDEs) are a group of new type organic pollutants
      with significant ecological risk. As flame retardants, they have been
      increasingly added to industrial products, and thus, resulted in more and more
      extensive pollution of air, water, sediment and soil as well as their relevant
      ecosystems. In view of the new environmental problem and based on limited
      available data, this paper approached the anthropogenic sources of PBDEs and
      their pathways of environmental exposure, and gave the possible occurrence and
      concentration of PBDEs in several living organisms and different human tissues.
      The toxic effects and ecological influences of PBDEs acting on animals and human
      beings, and their potential biological accumulation and magnification in
      ecosystems were analyzed in the aspects of hypothyroid, neurotoxicity, and
      reproductive and developmental toxicity, and the pivots of further researches on
      environmental exposure, ecological effects and human health influences of PBDEs
      were thus suggested.

PMID- 15852944
TI  - [Application of microsatellite DNA in molecular ecology and strategies for loci
      isolation].
AB  - Microsatellite DNA has been widely used as a good genetic marker in molecular
      ecology. This paper reviewed its application in molecular population biology,
      molecular environmental genetics, and molecular adaptation. The isolation of the
      loci is the basis of microsatellite DNA genetic analysis. Compared with the
      traditional isolation method by genomic library, some novel approaches carried
      out recently, such as enrichment library, PIMA and FIASCO, are more efficient and
      timesaving. The details and compare-analysis of these approaches were introduced,
      which would offer good choices for researches on molecular ecology.

PMID- 15852945
TI  - [Mercury concentration and its distribution in Nycticorax nycticorax and Chinese
      Ardeola bacchus fledglings at Huangpu District of Guangzhou City, China].
AB  - In this study, live fledglings of Nycticorax nycticorax and Ardeola bacchus at
      the Huangpu District of Guangzhou City were collected, and their primary feather,
      breast feather, tail feather, liver, chest muscle and egg shell were sampled for
      mercury determination. The results showed that these two heron species had a very
      similar distribution pattern of mercury concentration in their tissues and
      organs, i. e., tail feather > breast and primary feather > liver > chest muscle >
      egg shell. Ardeola bacchus had higher levels of mercury in all its tissues than
      Nycticorax nycticorax. There were significant interspecific differences in
      mercury level for breast feather and primary feather. Because the collection of
      breast feather is easier and not harmful to birds, it is better to use it rather
      than primary or tail feather to monitor environmental pollution. The mercury
      level in breast feather was ten times higher than that in liver, lower than that
      in tail feather, but not significantly different to that in primary feather. The
      mercury concentrations in the tissues of Nycticorax nycticorax and Ardeola
      bacchus from Huangpu District of Guangzhou were similar to those from the suburbs
      of Chengdu, Sichuan Province, but lower than those from Taihu Lake, Jiangsu
      Province and higher than those from Hong Kong.

PMID- 15852946
TI  - [Effects of no-tillage plus inter-planting and remaining straw on the field on
      cropland eco-environment and wheat growth].
AB  - The studies showed that under no-tillage plus inter-planting rice and wheat, the
      height of rice stubble remained on the field significantly affected light
      transmission rate, with an optimal height of 20-30 cm. No-tillage and straw
      remaining decreased soil temperature at noon in sunny days, but slightly
      increased it in the morning and evening, led to a less diurnal difference of soil
      temperature. The average diurnal soil temperature under no-tillage was higher in
      cloudy but lower in sunny days. Under no-tillage and straw-remaining, both the
      bulk density and the penetration resistance of topsoil increased, but no apparent
      adverse effect of them was observed on wheat growth. Under no-tillage, soil water
      content was higher under drought condition, and soil permeability after
      irrigation was better, which was propitious to the wheat growth. Straw-remaining
      significantly inhibited weeds, but led to the decrease of basic seedlings and
      enhanced the damage of freezing. Under no-tillage plus inter-planting, the
      individuals of effective ears decreased, while the kilo-grain weight increased.
      The grain yield was slightly but not significantly low under no-tillage plus
      inter-planting.

PMID- 15852947
TI  - [Assessing forest ecosystem health II. A case study].
AB  - On the bases of samples investment and related data collected by others, and with
      the method of health distance assessment and the ecosystem health index system of
      Korean pine and broad-leaved mixed forest established in prior paper, this paper
      attempted to assess the ecosystem health of Korean pine and broad-leaved mixed
      forest under various human disturbances. The results showed that the health
      degree was in the order of 20% intensity selective cutting stand (0.21) < 50%
      intensity selective cutting stand (0.44) < middle and mature birch stand (0.67) <
      youth birch stand (0.72) < Korean pine plantation (0.74) < larch plantation
      (0.77).

PMID- 15852949
TI  - [Relationship between tree-ring chronology of Larix olgensis in Changbai
      Mountains and the climate change].
AB  - The relationship of larch (Larix olgensis) radial growth in Changbai Mountains
      with climate change was assessed by dendrochronological techniques including
      correlation functions and single-years analysis. The results showed that larch
      growth was sensitive to environmental change, and temperature was the primary
      factor affecting larch growth. The larch growing in high and low elevations had a
      significantly different response to temperature. In high elevation, larch growth
      was significant correlated to the mean temperature of June, but in low elevation,
      it had a more complicated relationship to the environment. Besides the mean
      temperature of April and May, the temperature of last June and September and the
      humid index of last September significantly correlated with the larch tree ring
      width. Therefore, it was not the same relationship of the same tree species with
      different environmental gradients.

PMID- 15852948
TI  - [Stem respiration of Pinus koraiensis in Changbai Mountains].
AB  - In this paper, soil respiration chamber, a simple and precise method, was used to
      measure the stem respiration of trees. LI-6400-09 respiration chamber serving as
      a system is usually used in soil respiration, but we made polyvinyl chloride
      (PVC) collar and fixed it on the stem surface to measure the stem respiration.
      From May to October 2003, the stem respiration of Pinus koraiensis, the dominant
      tree species in Changbai Mountain, was measured in different time and different
      places using this technique. Meanwhile, the temperatures in the stems and in the
      forests were measured. The results showed that the stem respiration rate had a
      remarkably seasonal tendency with a single peak, the maximum was in August and
      the minimum was in February. The stem respiration rate had an exponential
      relationship with stem temperature, and the curve exponential regressions for
      stem respiration rate and temperature factor of trees with big DBH were better
      than those with small DBH. The stem respiration in different DBH trees was higher
      in the south stem face than that in the north stem face, and the variance of
      respiration rate between south and north decreased with a decrease of DBH trees.
      During the growing season from May to October, the average maintenance
      respiration accounted for 63.63% in different DBH trees, and the maintenance
      respiration contribution to total respiratory consumption increased with
      increasing DBH, which was 66.76, 73.29% and 50.84%, respectively. The stem
      respiration Q10 values ranged from 2.56-3.32 in different DBH of trees, and the
      seasonal tendency for stem R, and Rm in different DBH of trees was obtained by
      using respiration Q10. Therefore, the differences between different parts of stem
      and different DBH of trees should be considered in estimating the respiration
      model in ecosystem.

PMID- 15852950
TI  - [Root biomass of different stand-age Pinus yunnanensis forests and its
      distribution pattern in different soil depths].
AB  - With average-tree-specific sampling method, the authors measured the root biomass
      of Pinus yunnanensis forests with different stand ages in Yongren County, Yunnan
      Province. The results indicated that total root biomass increased from 8.50 t x
      hm(-2) in young stand (15-17 yr) to 11.70 t x hm(-2) in middle-aged stand (30-32
      yr), and to 18.91 t x hm(-2) in mature stand (60-130 yr). Among different stand
      age classes, the biomass of coarse roots (>10 mm) varied greatly (1.5-12.3 t x
      hm(-2)), whereas those of medium (5-10 mm) and fine (<5 mm) roots showed less
      variation (medium roots 1.4-1.6 t x hm(-2), fine roots 5.3-6.2 t x hm(-2)). The
      root biomass of mature stand decreased with soil depth, approximately 93% of
      total underground biomass being distributed in surface layer (0-30 cm), and only
      7% in deeper layer (30-115 cm).

PMID- 15852951
TI  - [Fate of Larix chinensis apex buds and its influence on branching pattern].
AB  - Using box-counting dimension method, this paper investigated the spatial
      occupation ability of different branching patterns related to the fate of Larix
      chinensis apex buds. The results showed that type I branching was beneficial to
      the branches to extend their spatial occupation, type II branching was beneficial
      to spread their areas, and type III branching was beneficial both to extend their
      spatial occupation and to spread their areas. As a whole, the death of apex buds
      could help branches to improve their spatial occupation ability and energy
      utilization efficiency, and play an important role in adjusting crown type, and
      hence, in improving its photosynthesis. The death of Larix chinensis apex buds
      was probably a compelled result of their rigorous living conditions.

PMID- 15852952
TI  - [Ecological plasticity of Larix chinensis population cones and seeds in Qinglin
      Mountain].
AB  - The study on 13 characters of cones and seeds of 6 Larix chinensis populations in
      Qinglin Mountain showed that there were significant differences in and among the
      populations. Except seed width and seed scale width, the other 11 characters were
      significantly different among populations. The variation coefficients of seed
      scale length, seed scale width, ratio of scale length to width, seed wing length,
      and seed wing width were larger among populations than in populations, while
      those of the other 8 characters were in adverse. Altitude had an obvious
      influence on the characters of cones and seeds, among which, seed width, scale
      width, scale length, seed wing length width, scale width, cone width, cone width,
      and the number of scales had a negative correlation with altitude, the ratio of
      scale length to width negatively correlated to slope, and scale width positively
      correlated to annual precipitation. The ratio of seed length to width and that of
      seed wing length to width showed a negative correlation to altitude.

PMID- 15852953
TI  - [Anatomical and nutrient features of plant leaves in Yuanjiang savanna valley].
AB  - Due to rain shadow effect, the valleys in southwestern China mountainous areas
      have hot and dry climate, and savanna or semi-savanna vegetations occur on the
      slopes of these valleys. Yuanjiang dry-hot valley is such a valley, which has a
      distinct dry season of about six months from November to next April. This paper
      studied the anatomical and nutrient features of the leaves of twenty plant
      species, including those on upland soils and hilly slopes. The results showed
      that compared with the species on upland soil and the rain forest, the leaves of
      the plants from savanna showed more xeromorphic features, such as thicker leaf
      thickness, greater leaf mass per area (LMA), smaller ratios of spongy/palisade
      tissues (S:P) and higher stomatal density (SD), which mainly came from the more
      severe drought in Yuanjiang savanna valley. Seven plant species in the savanna
      valley showed a shortage of nutrients in their leaves, and the leaf nutrient
      content was in order of 1.3% > Ca > N > K > 1% > Mg > P > S. Savanna had lower
      leaf mineral element concentrations than rain forest, but higher than other dry
      forests, including Asian heath forest and Bana forest. The differences in leaf
      nutrient concentrations between Yuanjiang valley savanna and other dry forests
      were mainly ascribed to the difference of soil nutrient contents, while those
      between valley savanna and rainforest were largely determined by the different
      plant biology. It could be concluded that the leaves of plant species in
      Yuanjiang savanna valley not only had obvious xeromorphic features, but also were
      deficit in nutrients.

PMID- 15852954
TI  - [Niche of the mosses on floor in Shanghai City].
AB  - The mosses on the floor of 22 sites at 20 main parks and 2 chemical plants in
      Shanghai were sampled, and 75 moss species were recorded. Their niche breadths
      were calculated by Levins equation. The results indicated that most moss species
      had rather narrow niche breadth, 68% of them with a niche breadth less than 0.1.
      The relationship between species number (N) and their niche breadth (B) followed
      the model N = 0.344 x e(-0.0377B), R = 0.9684. The niche overlaps of 39 main moss
      species (important value > 0.1) were calculated by Wang's equation. Based on
      their niche overlaps, the ordination plot of Principal Axes Analysis (PAA) and
      the Minimal Spanning Tree (MST) were drawn. The results showed that five
      ecological groups of the 39 moss species related to different habitats could be
      identified.

PMID- 15852955
TI  - [Age structure and growth pattern of Polytrichum juniperum populations in a mire
      of Changbai Mountains].
AB  - In this paper, the age structure and growth pattern of two Polytrichum juniperum
      populations with and without sporophytes in Hani mire of Changbai Mountains were
      studied by 'innate annual marker' method. The ramets of both populations were
      composed of 6 age classes, and their quantity and biomass showed a declining age
      structure, which was more obvious in the sporophyte produced population. No
      significant difference of biomass was found (P > 0.05) between the two
      populations. The dry material accumulation of the ramets in both populations
      increased with aging, and showed similar patterns of linear function. The ramets
      mean height of sporophyte-produced population was 6.17% shorter (P < 0.05) than
      the another, because sporophyte production limited the height growth. The ramets
      mean height also increased with aging, and showed similar patterns of linear
      function. In non-sporophyte produced population, the variation coefficient of
      ramets height was only 2.44%, which indicated the significance of similar height
      for ramets survival. In sporophyte produced population, the variation coefficient
      of ramets height was 25.07%, while that of ramets biomass was 8.25%, suggesting
      the significance of similar biomass to the reproduction of population. The
      biomass of ramets had a significantly positive correlation with height in both
      populations (P < 0.001), and no allometric growth was showed.

PMID- 15852956
TI  - [CO2 concentration character in broad-leaved Korean pine forest of Changbai
      Mountains].
AB  - The CO2 concentration in broad-leaved Korean pine forest of Changbai Mountains
      was measured continuously with a CO2 infra-red analyzer in 2003. The results
      showed that the CO2 concentration in the forest had striking characteristics of
      temporal-spatial variations, which were mainly influenced by the physiological
      processes of plants, soil respiration, and intensity of turbulence exchange. In
      growing season, the daily maximum and minimum CO2 concentration appeared mostly
      on the surface floor at about 5:00 in the early morning and at canopy location at
      about 15:00 in the afternoon, respectively. There was an obviously process of
      forest CO2 emission when the inversion broke at dawn. The average CO2
      concentration in forest was 377 micromol x mol(-1) in 2003, the maximum of
      monthly average appeared in January as 388 micromol x mol(-1), and the minimum of
      monthly average appeared in August as 352 micromol x mol(-1). The forest acted as
      CO2 source in night time and turned to sink in daytime, during growing season. In
      non-growing season, the forest acted as CO2 source in both daytime and night
      time, but still had a clear evidence of CO2 assimilation at noon, with canopy
      location during non-growing season.

PMID- 15852957
TI  - [Soil nitrogen mineralization under different land use patterns in
      Xishuangbanna].
AB  - Nitrogen (N) cycle is very important for forest ecosystem, and soil N
      mineralization rate is often used as the index of soil N availability and its
      losses. Using Close-Top incubation method, we measured the N mineralization rate
      in soils (0-15 cm) of monsoon evergreen broadleaf forest, seasonal rain forest,
      rubber plantation, heavily disturbed seasonal rain forest, Millettia laptobotrya
      secondary forest and upland rice field. The results showed that the net N
      mineralization rate and N nitrification rate were decreased in the sequence of
      heavily disturbed seasonal rain forest > Millettia laptobotrya secondary forest >
      seasonal rain forest > monsoon evergreen broadleaf forest > rubber plantation >
      upland rice field. Rubber plantation and upland rice field were the most
      seriously disturbed land use patterns. Their soil N storage and mineralization
      rate were very low and exhibited significant variations, compared with other land
      use patterns. Lower net N mineralization rate correlated with lower N storage,
      and also, with lower fungi numbers. The N mineralization rate in disturbed forest
      soil which had recovered for several years was similar to that in primary forest
      soil, but decreased significantly when the forests were converted to agricultural
      land.

PMID- 15852958
TI  - [Ecological effects of landscape structure on desertification process of Keerqin
      sandy land].
AB  - By the methods of ANOVA, correlative analysis and regression analysis, this paper
      studied the ecological effects of landscape structure on desertification process
      of a typical Keerqin sandy land at spatial and temporal scales. The results
      showed that any single factor of landscape structure indices had no remarkable
      impact on desertification (significant at 95%). Principal component analysis
      (PCA) on the landscape structure indices suggested that landscape structure
      played an important role in desertification, because it reflected the interaction
      between natural changes and human being's activities and was the feedback of the
      interaction. At temporal scale, the contribution rate of the first and second
      vectors reached 90.26% of total information. There was a single peak in
      desertification, which indicated that the influence of landscape structure was
      simple during the past four decades. At spatial scale, the contribution rate of
      the first and second vectors was up to 80.20%, and there were two peaks in
      desertification, which indicated that the influence of landscape structure was
      more complicated at spatial scale than at temporal scale.

PMID- 15852959
TI  - [Regional simulation of rice yield change under two emission scenarios of
      greenhouse gases].
AB  - Based on the newest emission scenarios of SO2 and greenhouse gases, i. e., the
      Intergovernmental Panel on Climate Change (IPCC) Special Report on Emission
      Scenarios (SRES) A2 and B2 scenarios, and by using RCM (Regional Climate Model)
      PRECIS and CERES-Rice model, this paper simulated the rice yield change in 2080
      at 50 x 50 km scale. The results showed that there was a great range of yield
      change across whole China. The yield would increase along the Changjiang River
      and in South China, and decrease in North and Northeast China. Because of the
      direct effect of CO2 on rice growth, the SRES A2 scenario would be more positive
      to the increase of rice yield than B2. In 2080, the total rice yield in whole
      China would increase under A2 emission scenario, while decrease under B2 emission
      scenario.

PMID- 15852960
TI  - [Analysis of paddy field evapotranspiration in North China and calculation of
      crop coefficient].
AB  - The potential evapotranspiration (ET0) values from 1951 to 2002 for the lower
      reaches of Liaohe Plain, North China, were estimated by Penman-Monteith equation,
      and the annual change in ET0 was analyzed. By using non-weighting lysimeters at
      Shenyang Experimental Station of Ecology (CAS) in North China, the daily
      evapotranspiration of flooded rice (Oryza sativa L.) at the interval of 10-11
      days was determined for eight seasons from 1993-2002 (except for 1997 and 1999).
      The results showed that the total evapotranspiration ranged from 581 mm to 695 mm
      during 1993 and 2002, averaged 634 mm. Both in dry and wet seasons, supplemental
      irrigation was essential in this region for the uneven distribution of rainfall
      and time. The average crop coefficient (Kc) for eight years from 1993 to 2002
      during the whole growth period was 1.32, with a second-degree polynomial change
      for the values of Kc during different rice growth stages.

PMID- 15852961
TI  - [Response of strawberry leaves photosynthesis to strong light and its mechanism].
AB  - In this paper, PAM-2000 portable chlorophyll fluorometer and HCM-1000
      photosynthesis measurement system were applied to measure the apparent quantum
      efficiency (AQY), initial fluorescence (Fo), maximal photochemical efficiency of
      PSII (Fv/Fm), maximal fluorescence (Fm), photochemical quenching (qP), non
      photochemical quenching (qN), actual quantum yield of PS II electron transport
      (phiPSII), electron transport rate (ETR), amount of inactive PS II reaction
      centers (Fi-Fo), Q(A) reduction rate, proportion of Q(B)-non-reducing PS II
      reaction centers [(Fi-Fo)/(Fp-Fo)], and energy-dependent quenching (qE),
      photoinhibitory quenching (qI) and state-transition quenching (qT) of non
      photochemical quenching of strawberry leaves. The results showed that the Fv/Fm,
      Fm, Fi-Fo and Q(A) reduction rate decreased in strong light and increased during
      subsequent dark recovery, but (Fi-Fo)/(Fp-Fo) was in reverse. They changed
      drastically within the first 10 minutes in strong light or in subsequent
      darkness. In strong light, phiPSII, ETR and qP increased firstly and then
      decreased, while qN decreased drastically firstly and then increased slightly.
      After exposure to strong light for 4 hours, the AQY of two varieties "Toyonoka"
      and "Houkouwase" decreased by 20.9% and 37.5%, respectively, and qE was 89.1% and
      87.1%, respectively in NPQ (qE + qI + qT). In strong light, "Toyonoka" showed
      less changes than "Houkouwase" in Fo, Fv/Fm, Fm, ETR, phiPSII and AQY. After
      treated with DTT, the Fv/Fm and Fm were lower, but Fo was much higher than
      control. It is deduced that in strong light, xanthophyll cycle-dependent non
      radiative energy dissipation and pH-dependent heat dissipation could play an
      important protective role against photo-damage to the photosynthetic apparatus in
      strawberry leaves.

PMID- 15852962
TI  - [Dynamics of soil phenols in continuous cropping solar greenhouse and their
      effects on disease resistance-related enzyme activities in cucumber root].
AB  - The study showed that under solar greenhouse condition, the contents of soil p
      hydroxybenzoic acid, ferulic acid and benzoic acid and their total amounts
      increased with increasing continuous cropping years, and were obviously higher
      after continuously cropped for 5, 7 and 9 years than for 1 and 3 years. Different
      concentration of soil phenols resulted in completely different effects on disease
      resistance-related enzyme activities in cucumber root, e. g., under lower
      concentrations (40 and 80 microg x g(-1)), the activities of phenylalanine (PAL),
      ployphenol oxidase (PPO) and peroxidase (POD) were increased, while under higher
      levels (120 and 160 microg x g(-1)), they were restrained. Therefore, the changes
      of soil phenol contents in continuous cropping solar greenhouse could be one of
      the essential factors affecting the disease-resistance of cucumber.

PMID- 15852963
TI  - [Effects of soil moisture on photosynthetic characteristics of different
      specialized end-uses winter wheat at their later growth stages and on their
      yields].
AB  - In this study, pot experiments with various cultivars of specialized end-uses
      winter wheat were carried out at Henan Agricultural University Research Station
      during 2001-2003. The results showed that as for cultivar Yumai 34, the values of
      its chlorophyll meter (SPAD), PSII activity (Fv/Fo) and maximal PSII light energy
      transformation efficiency (Fv/Fm) were the highest when soil moisture content was
      at 60% of field capacity (FC), but the photochemical quenching coefficient (qP),
      non-photochemical quenching coefficient (qN), apparent photosynthetic electron
      transport rate (ETR) and the ratio of PSII photochemical quantum yield (phi2)
      were all increased at 80% of FC. For high-yielding cultivar Yumai 49, its SPAD,
      qP, qN and ETR were higher at 80% of FC, but Fv/Fo, Fv/Fm and phi2 were less
      affected by FC. For cultivar Yumai 50, the values of its photosynthetic
      characteristics were the highest at 80% of FC, except that the qN value was the
      lowest. The yield and the relative content of grain protein of cultivar Yumai 34
      were also increased at 60% of FC. Furthermore, there was a significant difference
      among grain yields. The relative contents of grain protein of cultivars Yumai 49
      and 50 were improved at 40% of FC, while the highest yields were obtained at 80%
      of FC. There were significant differences in the grain yields of Yumai 49 and 50
      among different soil moisture treatments.

PMID- 15852964
TI  - [Variation of soil temperature before and after cultivation of marsh and its
      effect on soil thermal regime].
AB  - Marsh has important ecological and environmental functions and is sensitive to
      the global climate change, while the variation of soil temperature could better
      indicate the climate fluctuation. Our study showed that the annual and seasonal
      dynamic changes of soil temperature in marsh showed distinctly "sinusoid"
      character curve, whereas the mean annual temperature of different soil depths
      showed "U" feature. From May to September, the mean temperature at the topsoil
      (10 cm) of uncultivated marsh was 11.69 +/- 3.04 degrees C, while that of
      cultivated marsh was 15.80 +/- 3.41 degrees C. The soil respiration rate of
      uncultivated marsh in August and September was 156.41 +/- 76.91 mg x m(-2) x h(
      1) and 116.75 +/- 57.43 mg x m(-2) x h(-1), accounted for 14.6% and 13.1% of that
      of cultivated marsh, respectively. The soil temperature was significantly
      positively correlated with soil respiration.

PMID- 15852965
TI  - [Humus composition of black soil and its organo-mineral complexes under different
      fertility level].
AB  - Determinations by Kumada method showed that with the improvement of black soil
      fertility, the free and combined humus contents in soil and its different size
      organo-mineral complexes increased, but the humification degree of free humus
      decreased, which was more obvious in silt and fine sand size complexes. The
      organic carbon content in complexes, humus extraction rate, free humus content,
      and humification degree of free humic acid decreased with the increasing particle
      size of complexes. All free humic acids in fertile soil were Rp type, while in
      unfertile soil, they were Rp and B type. With the increasing particle size of
      complexes, the type of free humic acids changed in the sequence A type (clay)-->B
      type (silt)-->Rp type (fine sand). Combined form humic acid mainly belonged to A
      type, no matter what particle size the complex was. The improvement of soil
      fertility could make the humification degree of free humus in soil and its
      complexes decrease, and furthermore, result in type change. In black soil, the
      type change of free humic acid mainly occurred in silt size complex, and that of
      combined form humic acid mainly occurred in fine sand size complex.

PMID- 15852966
TI  - [Effects of N application and maize growth on N2O emission from soil].
AB  - With pot experiment and using static chamber-GC technique, this paper studied the
      effects of N application (150 and 300 mg x kg(-1) soil) and maize growth on N2O
      emission from soil. In maize-planted soil, the N2O emission rate increased with
      increasing N application rate, its peak appeared at seedling stage, and there was
      no significant correlation between N2O emission and air temperature. Contrarily,
      in bare soil, the peak of N2O emission rate occurred at the anaphase of the
      experiment, and there was a significant exponential correlation between N2O
      emission and air temperature. The total amount of N2O emission increased
      remarkably with increasing N application rate in both planted and bare soils. In
      comparing with bare soil, maize-planting reduced N2O emission by 92% and 87%,
      respectively at high and low N application rates, which suggested that maize
      planting not only affected the seasonal variation and magnitude of N2O emission
      from soil, but also altered the relationship between air temperature and soil N2O
      emission.

PMID- 15852967
TI  - [Effects of soil water status on gas exchange of peanut and early rice leaves].
AB  - The gas exchange characteristics of peanut and early rice leaves were
      investigated in experimental plots under different soil water conditions over a
      long growth period. The results showed that at the branching stage of peanut, the
      stomatal conductance (Gs) and transpiration rate (Tr) decreased slightly under
      mild and moderate soil water stress, while the net photosynthetic rate (Pn) and
      leaf water use efficiency (WUE) increased. The Gs/Tr ratio also increased under
      mild water stress, but decreased under moderate water stress. At podding stage,
      the Gs, Tr, Gs/Tr ratio and Pn decreased, while WUE increased significantly under
      mild and moderate water stress. The peanut was suffered from water stress at its
      pod setting stage. At the grain filling stage of early rice, the Gs, Tr and Gs/Tr
      ratio fluctuated insignificantly under mild and moderate water stress, while Pn
      and WUE increased significantly, with an increase in grain yield under mild water
      stress. It's suggested that the combination of Gs and Gs/Tr ratio could be a
      reference index for crop water stress, namely, crops could be hazarded by water
      stress when Gs and Gs/Tr decreased synchronously.

PMID- 15852968
TI  - [Effects of high concentration CO2 on lily growth and its two allelochemicals].
AB  - Under greenhouse condition, this paper studied the effects of different
      concentrations CO2 to the growth of oriental yellow poly-bud cut lily and to the
      two allelochemicals in lily leaves. The results showed that the optimum CO2
      concentration for Pn was 600 micromol x mol(-1). There was less impact on
      photosynthesis when continually supplying 600-1000 micromol x mol(-1) CO2 for 45
      days, probably due to the photosynthesis adaptability of new bulblets. 600
      micromol x mol(-1) CO2 could increase the stem height about 0.57 grades, and also
      had a positive effect on the growth of color bud. 600 micromol x mol(-1) and 800
      micromol x mol(-1) CO2 could markedly increase the contents of polyphenols and
      flavonoids in lily leaves, and there was no plant leaves withered, because the
      appropriate concentrations CO2 was beneficial to the Pn and to the formation and
      transformation of carbohydrates and allelochemicals, which increased the
      premunition of the plant. The contents of polyphenols and flavonoids in lily
      leaves reached the maximum when the concentration of CO2 was 600 micromol x mol(
      1).

PMID- 15852969
TI  - [Effects of transgenes insertion on pollen vigor and hybrid seed set of rice].
AB  - In this paper, the effects of transgenes insertion on the outcross potentiality
      of rice varieties were assessed by pollen vigor and hybrid seed set. The in vitro
      pollen germination rates of five transgenic rice lines transformed respectively
      with bar, crylAb, BADH and Xa21 gene were investigated, and compared with their
      relative receptor rice varieties. The results showed that there existed a
      significant difference in in vitro pollen germination rates between receptor rice
      varieties, but no significant difference was found between transgenic rice
      varieties and their relative receptors. The in vitro pollen germination rate for
      transgenic rice varieties varied from 0.416 to 0.584, similar to that of their
      relative receptors (0.400-0.574). Investigation on the hybrid seed set of 26 hand
      crosses showed that the inserted bar or crylAb gene had a significant effect on
      the hybrid seed set of receptors, while the effect of Xa21 gene was smaller. The
      hybrid seed set rate of non-transgenic rice in crosses with transgenic rice
      (pollen donor) was from 0.056 to 0.413, not different from that in crosses with
      their relative receptors (0.052-0.417). It's suggested that transgenes insertion
      had little effect on the outcross potentiality of rice varieties.

PMID- 15852970
TI  - [An approach to the screening index for low phosphorus tolerant rice genotype].
AB  - Screening and breeding low phosphorous (P) tolerant rice genotype is one of the
      effective alternatives to alleviate the scarcity of mineral P resource and to
      increase the utilization efficiency of P fertilizer. Selecting a simple and
      scientific screening index plays an important role in the screening and breeding
      program. In this study, a hydroponic culture experiment and a field trial were
      carried out to approach the screening index for low P tolerant rice genotypes.
      The results showed that among all the rice characters studied, total dry weight
      demonstrated a significant genotypic variation at both normal and low P supply
      (the CV was 21.73% and 19.54%, respectively). Relative total dry weight (low P
      supply/normal P supply) also demonstrated significant genotypic variation (CV was
      19.60%), which was significantly correlated to relative root dry weight, relative
      plant height, relative total P uptake, relative shoot P accumulation, relative P
      utilization efficiency and relative P concentration (P < 0.01). Therefore, the
      relative total dry weight of rice would be an important evaluation or screening
      index for the low P tolerance ability of rice at its seedling stage. The relative
      total dry weight of rice in hydroponic culture system was not correlated to the
      relative grain yield (minus-P/plus-P) in field trial, which meant that it could
      not be used as an index to evaluate the low P tolerance ability of rice. The
      internal P utilization efficiency of rice grown in low P solution was
      significantly correlated to that of rice grown in P-deficient soil (r = 0.798 *
      *, n = 8). Therefore, screening rice genotypes by using internal P utilization
      efficiency of rice grown in low P solution at seedling stage as screening index
      and subsequently testing in field trial would probably be an effective
      alternative to screen rice genotype with high P utilization efficiency.

PMID- 15852971
TI  - [A comparative study on asynchronous hatching and nestling growth of three heron
      species].
AB  - The study on the asynchronous hatching and nestling growth of three heron species
      (Ardeola bacchus, Egretta garzetta, Nycticorax nycticorax) in laboratory and
      field at the Changshan and Yuhang heron reserve in Zhejiang Province in 1996-1999
      showed that the herons migrated to the reserve in the first and second ten days
      of April, and left in late September. The average hatching period was 23.0 days
      for Ardeola bacchus, 23.9 days for Egretta garzetta, and 25.3 days for Nycticorax
      nycticorax. Nycticorax nycticorax had the highest hatching rate (95.45%),
      followed by Egretta garzetta (86.98%) and Ardeola bacchus (76.23%). The hatch
      ability of Nycticorax nycticorax (3.50) was higher than those of Egretta garzetta
      (3.38) and Ardeola bacchus (3.21). The increase of nestling weight was negatively
      related to the adult body size, but positively related to the hatching order. All
      nestlings developed well at their early growth stage, and then, there existed a
      significant difference among the nestlings based on the hatching order. The
      growth curves of the first three nestlings were similar and obviously better than
      that of the fourth, which indicated that early-hatched nestlings could obtain
      enough food, while the last one might be short of food. The optimal hatching
      quantity of the three heron species was assumed to be three offsprings.

PMID- 15852972
TI  - [Simulation of Plutella xylostella population control by granulosis virus].
AB  - By means of the life table of acting factors combinations and the theory of
      modern population system control, this paper evaluated the efficacy of different
      combinations of application dosage and times of granulosis virus on Plutella
      xylostella control. The results showed that with gradually recovered natural
      enemies, the second generation of Plutella xylostella in the field of spring
      flowering Chinese cabbage would increase 4.1 times if no control methods were
      carried out to the first generation. After applying a suspension of 0.25 LE/L
      (Larval equivalent) two times, the egg and larval numbers of the second
      generation Plutella xylostella were reduced significantly, but the index of
      population increase was still beyond 1, while applying a suspension of 0.5 LE/L
      two times or 1 LE/L one time at the peak of 2nd instar larvae of the 1st
      generation could significantly reduce the egg and larval numbers, and the index
      of population increase was only 0.13. Therefore, if used appropriately, the
      granulosis virus originated from Plutella xylostella could control the damage of
      Plutella xylostella effectively.

PMID- 15852973
TI  - [Accumulation of La(NO3)3 in mice liver and its genetic toxicity].
AB  - By using ICP-MS method, this paper determined the accumulation of La in mice
      liver after the mice being fed with La(NO3)3 water solution for thirty days, and
      through in vitro experiment, studied the effect of La(NO3)3 on the micronucleus
      rate of mice bone marrow cells and the cleavage action of La(NO3)3 on genome DNA
      to investigate the genetic toxicity of La. The results showed that when the
      treated concentration was 1000, 500, 300 and 50 microg x ml(-1), the amount of La
      in mice liver reached 1.46, 0.558, 0.529 and 0.083 microg x g(-1), respectively.
      Compared with control, the La amount in disposed groups' mice livers increased
      with increasing La(NO3)3 concentration in water (r = 0.980). T-test results
      showed that there existed significant differences in 1000, 500 and 300 microg x
      ml(-1) disposed groups when compared with the control (P < 0.05). The
      micronucleus rate of mice bone marrow cells increased with increasing La(NO3)3
      concentration in water (r = 0.853). The in vitro experiments showed that La(NO3)3
      could make DNA cleaved. It could be concluded that that La might be accumulated
      in organisms, and could induce the damage of genetic material in cells.

PMID- 15852974
TI  - [Allelopathy of root exudates from two genotypes soybeans on root pathogenic
      fungi].
AB  - With biological simulation experiment and chemical analysis, this paper studied
      the allelopathy of carbohydrates, amino acids and organic acids in the root
      exudates from two genotypes soybeans (9536 and Jilin 30) on the pathogenic fungi
      of root rot. The results showed that the water soluble carbohydrates in the root
      exudates from test soybeans significantly promoted the growth of Fusarium
      oxysporium and Fusarium semitectum at low concentrations and inhibited their
      growth at high concentrations, but had no evident influence on Gliocladium
      roseum. The water soluble amino acids from the root exudates demonstrated
      different actions, i. e., at middle and high concentrations, those from 9536
      significantly inhibited the growth of Fusarium oxysporium, Fusarium semitectum
      and Gliocladium roseum, while those from Jilin 30 mostly promoted their growth.
      The organic acids from the root exudates of 9536 and Jilin 30 significantly
      inhibited the growth of Fusarium oxysporium, Fusarium semitectum and Gliocladium
      roseum. It's suggested that there existed interactions between the root exudates
      of the two genotypes soybeans and the pathogenic fungi of root rot. Different
      genotypes of soybean may have different allelopathy on pathogenic fungi of root
      rot.

PMID- 15852975
TI  - [Construction of Bacillus thuringiensis labeled recombinant strain and horizontal
      transfer of its cry1Ac10 gene].
AB  - A recombinant plasmid pBMBZGC10 was obtained by the ligation of gfp-cry1Ac10
      fusion gene and vector plasmid pAD4412, which was then introduced by gene pulser
      into acrystalliferous strain CryB, and a recombinant strain CryB(pBMBZGC10) was
      obtained. Different fermentative solutions of recombinant strain were used for
      multi-spraying on Brassica pekinesis, Ipomoea aquatica and Lycopersicon
      esculentum leaves. The results of fluorescent detection and PCR amplification
      revealed that cry1Ac10 gene did not transfer into indigenous bacteria,
      actinomyces and fungi in test soil, and could not be detected in roots, stems and
      leaves of test plants.

PMID- 15852976
TI  - [Field distribution pattern and metabolic activity of AM fungi and their effects
      on Ipomoea batatas growth].
AB  - The study showed that after eight weeks of inoculating sweet potato seedlings
      with AM fungus Glomus intraradices BEG141 under field condition, the shoot dry
      weight, individuals of tuber and their fresh weight, as well as the P uptake by
      the plant increased significantly. Compared with the control, the root
      colonization rate, extraradical hyphal density and intraradical alkaline
      phosphatase (ALP) activity were greatly increased. After inoculation with BEG141,
      the total and succinate dehydrogenase (SDH)- active hyphae paralleling with ridge
      were much more than those in underside direction, while there was no significant
      difference in different directions in the control. The increase of intra- and
      extraradical active hyphae density and the change of AM fungus distribution
      pattern after inoculation with mycorrhizal fungi may be the main reasons for the
      growth improvement of sweet potato.

PMID- 15852977
TI  - [Ecological relationships among artificial vegetations during their restoration
      in Antaibao mining area].
AB  - By the methods of TWINSPAN, DCA and DCCA, and from the aspects of the relations
      between plant species, communities and environmental factors, this paper studied
      the ecological relationships among artificial vegetations during their
      restoration in Antaibao mining area. 63 collected quadrates were classified into
      12 community types by TWINSPAN, and the distribution of the communities could
      comprehensively reflect the influence of environmental factors. DCA ordination
      indicated that soil water content, which was increased with restoration time, was
      the main factor restricting the distribution of the communities. DCCA ordination
      showed that soil organic matter content was the decisive factor to the
      development of communities.

PMID- 15852978
TI  - [Comparison of nutrient removal ability between Cyperus alternifolius and
      Vetiveria zizanioides in constructed wetlands].
AB  - In order to compare the nutrient removal ability of Cyperus alternifolius and
      Vetiveria zizanioides, a 17.0 m2 subsurface flow wetland covered with Cyperus
      alternifolius and another 13.3 m2 one covered with Vetiveria zizanioides were
      constructed for piggery wastewater treatment, and the biomass as well as the N,
      P, Cu and Zn contents in the root and shoot of the plants was measured by the end
      of each season. The results showed that the below-ground biomass of V.
      zizanioides was greater than that of C. alternifolius. By the contrary, the above
      ground biomass of C. alternifolius was greater than that of V. zizanioides. The
      annual biomass yield of C. alternifolius was 2.3 times higher than that of V.
      zizanioides,which was 3406.47 g x m(-2) and 1483.88 g x m(-2), respectively. The
      N concentration in C. alternifolius tissue was higher than that in V. zizanioides
      tissue, being 22.69 mg x g(-1) and 15.44 mg x g(-1) respectively, and similarly,
      the P concentration in C. alternifolius tissue was higher than that in V.
      zizanioides tissue, being 6.09 mg x g(-1) and 5.47 mg x g(-1) respectively. The
      Cu and Zn concentrations in C. alternifolius tissue were a little higher than
      those in V. zizanioides. 68.72 g N x m(-2) and 18.49 g P x m(-2) were removed by
      harvesting C. alternifolius vegetation, while 8.93 g N x m(-2) and 3.69 g x P m(
      2) were removed by harvesting V. zizanioides vegetation. It was concluded that
      the removals of N, P, Cu and Zn by harvesting vegetation were 4-7 times higher in
      C. alternifolius wetland than in V. zizanioides wetland.

PMID- 15852979
TI  - [Tolerance of Arundo donax to heavy metals].
AB  - This paper studied the tolerance of Arundo donax grown in a simulated heavy
      metals polluted wetland, and determined the biological characters and chlorophyll
      contents of the plant at its different growth stages as well as the changes of
      soil heavy metals contents. The results showed that Arundo donax could survive in
      the wetland when the concentrations of Cu2+, Pb2+, Cd2+, Zn2+, Ni2+ and Hg2+ were
      100 mg x kg(-1) and Cr6+ concentration was 50 mg x kg(-1). During 40 days growth
      period, the chlorophyll content decreased by 20%-56% and the leaf became soft
      with its tip withered, but the plant still grew. Compared with control, Arundo
      donax in the polluted wetland was slight and yellow-green, but the impact on
      plant height was inconspicuous. Arundo donax treated with 100 mg x kg(-1) Cr6+
      grew slowly with its root stock rotted, and its leaves withered in a short time,
      indicating that the plant could not tolerate the pollution of high concentration
      Cr6+. The concentrations of soil heavy metals declined with the growth of the
      plant, probably due to the translocation of heavy metals from peripheral soil to
      rhizosphere and the phytoextraction and phytovolatilization, because the heavy
      metals contents in rhizosphere were much higher than those in the bulk soil in
      the test jar. The characters of large biomass, exuberant root and good
      adaptability of Arundo donax suggested its great potential in remediation of
      polluted soils. The study on the application of Arundo donax to phytoremediation
      is of realistic significance.

PMID- 15852980
TI  - [Effects of aluminum stress on photosynthetic characters of soybean].
AB  - With three soybean (Glycine max) varieties Zhechun No. 2, Zhechun No. 3 and 9703
      as test materials, this paper studied the effects of different aluminum (Al)
      concentration on their photosynthetic characters. The results showed that the
      leaf chlorophyll content decreased by 5%-35% when Al concentration increased. Al
      also affected various physiological functions, e. g., stomatal resistance
      increased by 10%-35%, stomatal conductance decreased by 10%-40%, photosynthetic
      and transpiration rate decreased by 5%-40% and 20%-50%, respectively, and water
      utilization efficiency decreased by 15%-50%. Al stress could inhibit the
      photosynthesis of soybean leaves, and the inhibition was more serious in
      vegetative than in reproductive growth period. In addition, three test soybean
      varieties had definite genetic difference in response to Al toxicity.

PMID- 15852981
TI  - [Phototactic behavior of Daphnia carinata as an indicator of chromium
      biotoxicity].
AB  - The study on the phototactic behavior of Daphnia carinata clone Dc42 as an
      indicator of chromium biotoxicity showed that the phototaxis inhibition ratio
      (Rpi) of D. carinata could better indicate the chromium status in water. There
      was a negative linear correlation between phototactic index (Ip) and Cr6+
      concentration in standardized K2Cr2O7 solutions (R2=0.8089, P<0.001). The
      detection limit of Cr6+ by Ip was 0.056 mg x L(-1), much lower than that of LC50
      or EC50, and the mean precision index for detection reached up to 5.46%, which
      suggested the sensitivity, precision and reliability of this method in monitoring
      chemicals biotoxicity.

PMID- 15852982
TI  - [Eco-toxicity diagnosis on sediments of petroleum wastewater irrigation channel].
AB  - Sediment samples were collected from several sites in the upper, mid and lower
      reaches of the petroleum wastewater irrigation channel in eastern Shenyang of
      China, and the concentrations of their Cu, Zn, Pb, Cd and mineral oil were
      analyzed. The results showed that the pollutants were accumulated in all of
      sediment samples, with 408-118,300 mg x kg(-1) mineral oil, 17.83-78.53 mg x kg(
      1) Cu, 35.76-155.16 mg x kg(-1) Zn, 8.50-31.03 mg x kg(-1) Pb and 0.1-1.0 mg x
      kg(-1) Cd. The sediments showed an inhibition or stimulation effect on plant root
      elongation and a lethal and sub-lethal effect on earthworm. The inhibition rate
      of root elongation based on germination test was -29.81 to 93.8%. During 14 d
      exposure, the maximum mortality rate of earworm was 100%, and during 14d and 28d
      exposure, the inhibition rate of its body weight growth was -36.6%-(-)6.08% and 
      40.4%-6.1%, respectively. The study indicated that a long-term irrigation with
      petroleum wastewater resulted in the accumulation of pollutants in channel
      sediments and enhanced eco-toxicity.

PMID- 15852983
TI  - [Evaluation on self-pollution of marine culture in the Yellow Sea and Bohai Sea].
AB  - This paper studied the respective contribution of feeding and non-feeding marine
      culture on seawater and red tide occurrence. The results showed that the annual
      output of marine had a positive correlation with the nutrients and COD in the
      Yellow Sea and Bohai Sea, of which, the correlation between DIN content and
      shrimp yield was significant. The output also had a positive correlation with the
      occurrence times of red tide recorded in the Yellow and Sea Bohai Sea. These
      results illustrated that the self-pollution of marine culture had a significant
      influence on the eutrophication and red tide occurred in the neighboring waters.
      It was estimated that the amounts of N, P and COD entered into seawater through
      the marine culture in the Yellow Sea and Bohai Sea accounted for 2.8%, 5.3% and
      1.8% of the amounts of corresponding land-based pollutants entered to the sea,
      respectively. Although the discharge of the pollutants produced by marine culture
      was less than that produced by other human activities, some local waters,
      especially dense marine culture areas, would bring out some additive effects on
      environment. Therefore, the pollutants discharged by marine culture were very
      likely to be an important factor stimulating the eutrophication and red tide
      occurrence in coastal waters, which should be paid adequate attention.

PMID- 15852984
TI  - [Interrelation between plant species diversity and soil environmental factors in
      bird island of Qinghai Lake].
AB  - The study on the relationship between plant species diversity and soil factors in
      the bird island of Qinghai Lake indicated that this island was a low diversity
      district, its Shannon-Wienner index and species richness decreased with the
      increasing soil available K, water soluble salt concentration and pH, and there
      were significant linear and quadratic correlations between them. Stepwise linear
      regressions showed that soil available K and water soluble salt were the key
      factors to estimate Shannon-Wienner index and species richness in this island,
      respectively, and no correlation was found between species evenness and soil
      factors.

PMID- 15852985
TI  - [Nitrite content of common vegetables in Wuhu City].
AB  - Laboratory analysis was carried out to study the nitrite content and its
      affecting factors of 10 common vegetables in terminal markets of Wuhu City. The
      results showed that the nitrite content of root or stem- and fruit vegetables was
      lower than the national standard, but that of leaf vegetables exceeded the
      standard seriously. The nitrite in vegetables increased significantly with
      storage time. Stored under room temperature, the test vegetables had 1-2 times
      higher nitrite content at the fourth day than at the first day, but storage under
      low temperature, i. e., in refrigerator, could hinder the increase of nitrite
      content in vegetables, and the daily increase was only 1/2-1/6 times of that
      under room temperature. Abluent could eliminate nitrite effectively, whose
      efficiency was 1-5 times higher than that of tap water.

PMID- 15852986
TI  - [Effects of exogenous jasmonic acid-induced plant responses on development and
      growth of Plutella xylostella].
AB  - Jasmonic acid (JA) is a naturally occurred growth regulator found in higher
      plants and a main signal molecule carrying information about injury. Its
      increased concentration in plants infested by herbivores can induce the wounded
      plants to produce defense responses which will affect herbivores. The application
      of exogenous JA to plants could imitate the effects of herbivores infestation.
      This study showed that applying exogenous JA on cabbage plants did not affect the
      survival of Plutella xylostella larvae, but retarded their development and
      reduced the pupal weight and female fecundity.

PMID- 15852987
TI  - Influence of intra-aortic balloon pumping on cerebral blood flow pattern in
      patients after cardiac surgery.
AB  - BACKGROUND AND OBJECTIVE: The effects of intra-aortic balloon pumping (IABP) on
      cerebral perfusion are still a matter of debate. End-diastolic reversal of blood
      flow in cerebral arteries has been observed in a small number of patients. We
      prospectively investigated the incidence and the amount of transient cerebral
      artery blood flow reversal during balloon pumping in patients recovering from
      cardiac surgery. METHODS: In 23 patients receiving IABP support, blood flow
      velocities in the right middle cerebral artery were assessed by transcranial
      Doppler-sonography. Additionally, systemic haemodynamics were monitored. In each
      patient, measurements were performed at three different pump settings: without
      support, assist ratio 1 : 1 and assist ratio 1 : 2. RESULTS: In 8 of 23 patients,
      balloon pumping caused a transient diastolic reversal of blood flow in the middle
      cerebral artery during balloon deflation. Antegrade mean flow velocity in the
      middle cerebral artery significantly increased from 57 +/- 27 to 61 +/- 26
      (assist ratio 1 : 1) and 61 +/- 29 cm s(-1) (assist ratio 1 : 2) (P < 0.05).
      Taking transient blood flow reversal into account, net mean flow velocity did not
      increase with balloon pump support. Systemic haemodynamic parameters remained
      unchanged. CONCLUSION: Left ventricular support with IABP significantly changed
      flow patterns in basal cerebral arteries of our patients. In 35% of patients,
      support resulted in a transient reversal of intracranial blood flow which
      counterbalanced a slight increase in mean antegrade flow.

PMID- 15852988
TI  - The effect of inhalational anaesthetics on QTc interval.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to assess time dependent
      cumulative effects of three different inhalation anaesthetics on QTc interval
      during the maintenance of anaesthesia. METHOD: Seventy-five ASA I-II male
      patients undergoing inguinal herniorrhaphy were randomly allocated into three
      groups. No premedication was given. Anaesthesia was induced with thiopental and
      tracheal intubation was facilitated by vecuronium in all groups. Anaesthesia was
      maintained with 0.8% halothane (Group I) (n = 25), 1% isoflurane (Group II) (n =
      25), or 2% sevoflurane (Group III) (n = 25) and 66% nitrous oxide in oxygen.
      Three lead electrocardiogram recordings were taken before induction, 2, 5, 10,
      15, 30 and 45 min after induction and after extubation. Heart rate, systolic,
      diastolic, mean arterial pressure and SpO2 were recorded at the same time. Heart
      rate and corrected QT interval were evaluated by using Bazett's formula.
      Multivariate analysis of variance for repeated measures was used to determine
      intergroup and intragroup differences. RESULTS: There was no statistically
      significant difference in the baseline QTc values of the groups. There was no
      difference between QTc values with halothane and sevoflurane. There was a
      difference between QTc values with isoflurane and those with the other two
      inhalation anaesthetics (P < 0.05). Although QTc values in the isoflurane group
      were higher at all times, the critical value of 440 ms was not exceeded.
      CONCLUSION: We conclude that halothane 0.8%, isoflurane 1% and sevoflurane 2% do
      not prolong QTc interval.

PMID- 15852989
TI  - Pressure-volume curve variations after a recruitment manoeuvre in acute lung
      injury/ARDS patients: implications for the understanding of the inflection points
      of the curve.
AB  - BACKGROUND AND OBJECTIVE: Although the pressure-volume (P-V) curve has been
      proposed in the management of mechanically ventilated patients, its
      interpretation remains unclear. Our aim has been to study the variations of the P
      V curve after a recruitment manoeuvre (RM). Our hypothesis was that the lower
      inflection point (LIP) represents the presence of compressive atelectases, so it
      should not change after lung recruitment, while the upper inflection point (UIP)
      reflects reabsorptive atelectases, and an effective recruitment should result in
      changes at this level. METHODS: Two P-V curves (quasi-static method) separated by
      an RM (40 cmH2O, two consecutive manoeuvres) were plotted in 35 postoperative
      patients with criteria of acute lung injury/acute respiratory distress syndrome
      (ARDS). LIP, UIP and expiratory inflection point (EIP) were defined as the first
      point where the curve consistently starts to separate from the line. RESULTS: One
      to six measurements were obtained per patient (73 procedures). Neither the lower
      nor the EIPs varied significantly after the RM (P = 0.11 and 0.35, respectively).
      An UIP was observed in 18 curves (25%) before the RM and disappeared on nine
      occasions after the recruitment. Similar results were obtained when first
      measurements only were analysed, and when the cause (pulmonary vs.
      extrapulmonary), severity of lung injury or duration of mechanical ventilation at
      first measurement were studied. CONCLUSIONS: An RM does not modify the LIP
      significantly, but induces the disappearance of the UIP in 50% of the cases in
      which this point is found.

PMID- 15852990
TI  - Effects of isovolaemic haemodilution on oxygenation of liver and skeletal muscle.
AB  - BACKGROUND AND OBJECTIVE: Hydroxyethyl starch is frequently used for volume
      substitution during surgical procedures and for isovolaemic haemodilution.
      Haemodilution has also been shown to improve tissue oxygen tension in skeletal
      muscle: However, effects of this volume substitute on tissue oxygen tension of
      the liver during haemodilution remains unknown. METHODS: Fourteen foxhounds were
      anaesthetized with fentanyl/midazolam and mechanically ventilated with 30%
      oxygen. Following splenectomy animals were randomly assigned to a control group
      without haemodilution but fluid substitution with Ringer's lactate (Group C) or
      underwent isovolaemic haemodilution to a haematocrit of 25% with hydroxyethyl
      starch 70/0.5 (Group H). Haemodynamic parameters and oxygen transport during 100
      min following isovolaemic haemodilution were measured. Liver oxygen tension was
      recorded using a flexible polarographic electrode tonometer, whereas in the
      muscle a polarographic needle probe was used. RESULTS: Animal characteristics and
      baseline haematocrit were similar in both groups. At baseline the tissue oxygen
      tension of liver and skeletal muscle were not different between groups.
      Haemodilution with hydroxyethyl starch 70/0.5 provided augmentation of mean liver
      tissue oxygen tension (baseline: 46 +/- 13 mmHg; 20 min: 60.3 +/- 12 mmHg; 60
      min: 60 +/- 16 mmHg; 100 min: 63 +/- 16 mmHg; P < 0.05 vs. baseline), while
      oxygen tensions in Group C remained unchanged (baseline: 48 +/- 16 mmHg; 20 min:
      52 +/- 19 mmHg; 60 min: 49 +/- 12 mmHg; 100 min: 52 +/- 16 mmHg) and no
      differences could be detected between groups. Oxygen tension in skeletal muscle
      changed as follows: Group H - baseline: 24 +/- 32 mmHg; 20 min: 32 +/- 3 mmHg; 60
      min: 33 +/- 7 mmHg; 100 min: 33 +/- 11 mmHg. Group C - baseline: 22 +/- 6 mmHg;
      20 min: 21 +/- 3 mmHg; 60 min: 24 +/- 4 mmHg; 100 min: 18 +/- 4 mmHg (P < 0.05
      vs. baseline, p < 0.05 vs. Group C). CONCLUSION: In this animal model,
      isovolaemic haemodilution with hydroxyethyl starch 70/0.5 increased tissue oxygen
      tension in liver and skeletal muscle in comparison with baseline values. However,
      when compared between groups haemodilution only resulted in an increase of tissue
      oxygen tension in the muscle but not in the liver.

PMID- 15852991
TI  - Melatonin vs. midazolam premedication in children: a double-blind, placebo
      controlled study.
AB  - BACKGROUND AND OBJECTIVE: Unlike midazolam, melatonin premedication is not
      associated with cognitive impairment in adults despite its anxiolytic properties.
      The use of melatonin as a premedicant in children has not been reported. This
      randomized, double-blind, placebo-controlled study compared the perioperative
      effects of different doses of melatonin and midazolam in children. METHODS: Seven
      groups of children (n = 15 in each) were randomly assigned to receive one of the
      following premedicants. Midazolam 0.1, 0.25 or 0.5 mg kg(-1) orally, melatonin
      0.1, 0.25 or 0.5 mg kg(-1) orally each mixed in 15 mg kg(-1) acetaminophen, or
      placebo only (15 mg kg(-1) acetaminophen). Anxiety and temperament were evaluated
      before and after administration of the study drug, on separation from parents and
      on the introduction of the anaesthesia mask. At week 2 postoperatively, the
      behaviour of the children was measured by the Post Hospitalization Behaviour
      Questionnaire. RESULTS: Melatonin or midazolam each in doses of 0.25 or 0.5 mg
      kg(-1) were equally effective as premedicants in alleviating separation anxiety
      and anxiety associated with the introduction of the anaesthesia mask. A trend was
      noted for midazolam to prolong recovery times as the dosage increased. The use of
      melatonin was associated with a lower incidence (P = 0.049) of excitement at 10
      min postoperatively, and a lower incidence (P = 0.046) of sleep disturbance at
      week 2 postoperatively than that observed with midazolam and control groups. No
      postoperative excitement was noted in the melatonin groups at 20, 30 and 45 min.
      DISCUSSION: Melatonin was not only as effective as midazolam in alleviating
      preoperative anxiety in children, but it was also associated with a tendency
      towards faster recovery, lower incidence of excitement postoperatively and a
      lower incidence of sleep disturbance at week 2 postoperatively.

PMID- 15852992
TI  - Decreased mivacurium infusion rate and delayed neuromuscular recovery after
      metoclopramide: a randomized double blind placebo-controlled study.
AB  - BACKGROUND AND OBJECTIVE: Metoclopramide is an antiemetic drug which inhibits
      plasma cholinesterase activity. We have compared the mivacurium infusion
      requirements and neuromuscular recovery after administration of metoclopramide to
      a group of adults compared to a control group. METHODS: Forty-five patients were
      randomized into three groups. Two groups received either 10 or 20 mg of
      intravenous (i.v.) metoclopramide and the third group received i.v. saline.
      Metoclopramide and saline were given 5 min before i.v. induction of anaesthesia.
      Plasma cholinesterase activity was measured before induction and 30 min after
      metoclopramide or saline injection. Neuromuscular block was monitored by
      accelerography using single and train-of-four (TOF) stimulation. The mivacurium
      intubation dose was followed by an infusion titrated every 5 min to maintain 95%
      block until the end of surgery when the infusion was stopped. Recovery from
      mivacurium was then monitored until complete. RESULTS: Mivacurium infusion rates
      were significantly lower in the metoclopramide groups. After 45 min of infusion,
      the infusion rates were 1.82 +/- 0.8 and 2.1 +/- 1 microg kg(-1) min(-1) in the
      20 and 10 mg metoclopramide groups, respectively, and 6.8 +/- 2.7 in the saline
      group. Time to recovery of TOF to greater than 90% was significantly prolonged in
      both metoclopramide groups compared to the saline group: 33.2 +/- 7.2 and 29.5 +/
      10.3 min in the metoclopramide 20 and 10 mg groups, respectively, compared to 22
      +/- 3.9 in the saline group (P < 0.001 for the 20 mg group compared to control).
      CONCLUSION: Metoclopramide enhances the effect of a mivacurium infusion.

PMID- 15852993
TI  - Initial distribution volume of glucose is correlated with intrathoracic blood
      volume in hypovolaemia and following volume loading in dogs.
AB  - BACKGROUND AND OBJECTIVE: Initial distribution volume of glucose (IDVG) reliably
      measures the central extracellular fluid volume in the presence of fluid gain or
      loss. We hypothesized that IDVG has a close relationship with intrathoracic blood
      volume (ITBV), which has recently been used as an indicator of cardiac preload.
      We therefore examined whether IDVG can correlate with ITBV in various fluid
      volume states. METHODS: Fourteen anaesthetized mongrel dogs were mechanically
      ventilated. ITBV and cardiac output were measured by single transpulmonary
      thermodilution technique. IDVG and indocyanine green derived plasma volume (PV
      ICG) were determined by the administration of 100 mg kg(-1) glucose and 0.5 mg
      kg(-1) indocyanine green solutions, respectively, and calculated by applying a
      one-compartment model. Three sets of measurements were performed before and after
      haemorrhage (30 mL kg(-1) and subsequent fluid volume loading (90 mL kg(-1) of
      lactated Ringer's solution). RESULTS: A linear correlation was observed between
      IDVG and ITBV (r2 = 0.52, n = 42, P < 0.001) and between PV-ICG and ITBV (r2 =
      0.44, n = 42, P < 0.001) throughout the procedures. A linear correlation was also
      observed between changes in IDVG and those in ITBV (r2 = 0.76, n = 28, P <
      0.001). The ITBV/IDVG ratio during normovolaemia was 0.26 +/- 0.04, which
      remained unchanged during the procedure. CONCLUSION: Results showed that that
      IDVG has a linear correlation with ITBV, and support the concept that IDVG
      measurement has potential as a surrogate measure of ITBV in various fluid volume
      states.

PMID- 15852994
TI  - Insignificant effect of desflurane-fentanyl-thiopental on hepatocellular
      integrity--a comparison with total intravenous anaesthesia using propofol
      remifentanil.
AB  - BACKGROUND AND OBJECTIVE: Inhalational anaesthetics have been associated with
      hepatotoxicity. Even desflurane, with its low solubility in blood and tissues,
      and its minimal hepatic biotransformation, is known to affect hepatic integrity.
      The effects of propofol on hepatic function are, however, a matter of
      controversy. Alpha-glutathione S-transferase (alpha-GST), a sensitive and
      specific biomarker for hepatic integrity, was measured to assess the influence of
      total intravenous anaesthesia (TIVA) with propofol vs. anaesthesia with
      desflurane. METHODS: Forty-two patients scheduled for elective prostatectomy were
      randomly allocated to receive either desflurane, fentanyl and thiopental
      (desflurane group) or propofol and remifentanil (TIVA group). Depth of
      anaesthesia was guided by bispectral index. Plasma concentrations of alpha-GST
      and aminotransferases were measured before induction of anaesthesia (TO), at the
      end of surgery (T1), as well as 2 h (T2) and 24 h (T3) postoperatively.
      Haemodynamic parameters and bispectral index values were documented. RESULTS:
      alpha-GST increased significantly in the desflurane group from TO (3.0 +/- 2.2
      microg L(-1)) to T1 and T2 (5.5 +/- 4.3 and 5.6 +/- 3.7 microg L(-1),
      respectively), whereas no changes were seen in the TIVA group. alpha-GST values
      above the normal upper limit (> 7.5 microg L(-1)) were seen in 24% of the
      patients receiving desflurane. Aminotransferases remained unchanged in both
      groups throughout the study period. CONCLUSIONS: The use of propofol as part of a
      TIVA regimen seems to have no influence on hepatocellular function during and
      after surgery. In contrast, patients receiving desflurane showed a transient
      slight, but significant, increase of alpha-GST to above the normal upper limit
      after anaesthesia, although this was without further clinical relevance.

PMID- 15852995
TI  - Ketamine enantiomers differentially relax isolated coronary artery rings.
AB  - BACKGROUND AND OBJECTIVE: It has been shown that racemic ketamine increases
      coronary blood flow and that this effect is at least in part due to a direct
      vasorelaxing effect of this substance. This study was designed to determine
      whether ketamine might stereoselectively relax isolated porcine coronary
      arteries. METHODS: Using the model of isolated vessels we studied the effects of
      S(+) ketamine, R(-) ketamine, and racemic ketamine (5-500 microg mL(-1)) on
      artery strips pre-contracted by either potassium chloride (KCl) or prostaglandin
      F2alpha (PGF2alpha). To elucidate possible mechanisms of action these experiments
      were repeated in the presence of one of the following compounds: N(omega)-nitro-L
      arginine (L-NNA), indomethacin, glibenclamide, and tetraethylammonium (TEA)
      chloride, an inhibitor of the BK(Ca) K+ channel. RESULTS: Both isoforms and
      racemic ketamine relaxed isolated coronary arteries in a concentration-dependent
      manner in concentrations beyond those used in clinical practice. S(+) ketamine
      exerted the strongest vasorelaxing effect, followed by racemic ketamine and R(-)
      ketamine. Pretreatment with L-NNA, indomethacin, or glibenclamide did not alter
      the vasodilating properties of ketamine, whereas TEA chloride significantly
      attenuated the vasorelaxing effects of all the three forms of ketamine.
      CONCLUSIONS: Ketamine dilates coronary arteries in vitro when administered in
      high concentrations. There is a stereoselective difference with a stronger
      vasorelaxing effect of S(+) ketamine compared to racemic and R(-) ketamine. The
      impact of TEA chloride suggests that the activation of the BK(Ca) channel may
      contribute to the vasodilating effect of ketamine.

PMID- 15852996
TI  - Mechanisms of ketamine action on lipid metabolism in rats.
AB  - BACKGROUND AND OBJECTIVE: This study was conducted to determine the effect of
      ketamine on metabolic homoeostasis and particularly in lipoprotein lipase (LPL)
      activity in adipose tissue. METHODS: Sixty male Wistar rats were divided into six
      groups of 10 each. Group A served as controls, while Groups B-F received,
      respectively, ketamine 60, 80, 100, 120 and 140 mg kg(-1) intraperitoneally. The
      animals were sacrificed 20 min after the administration of ketamine. Insulin
      concentrations in plasma and total cholesterol, triglyceride, high-density
      lipoprotein (HDL) and free fatty acid (FFA) concentrations in serum were
      measured. LPL activity in adipose tissue and medium-chain acyl-CoA dehydrogenase
      (MCAD) content in muscle were determined. RESULTS: FFA concentrations in serum
      significantly increased from the second lowest dose of ketamine. Insulin
      concentrations in plasma did not exhibit any significant difference between
      groups. MCAD levels were 0.5-fold more in Group F than in Group A, while there
      were no significant differences between control group and Groups B-E.
      Furthermore, high concentrations (120 and 140 mg kg(-1)) of ketamine interfered
      with in metabolic homoeostasis by significantly reducing LPL activity, thus
      elevating triglyceride concentrations in serum without affecting cholesterol and
      HDL metabolism. CONCLUSIONS: Ketamine induces various metabolic effects due to
      changes in adipose LPL activity and MCAD levels in muscles. These findings seem
      to be significant only at high doses.

PMID- 15852997
TI  - An Italian survey of severe head trauma management during extracranial surgery.
AB  - BACKGROUND AND OBJECTIVE: Anaesthetic drugs and procedures interfere with
      secondary brain injury following severe head trauma, yet studies regarding the
      anaesthetic management of these patients are lacking. We investigated the
      behaviour of Italian anaesthetists regarding this topic. METHODS: A questionnaire
      investigating the approach to a patient with severe head trauma requiring an
      urgent splenectomy for ruptured spleen was sent to 250 Italian anaesthetists.
      Questions regarded the pre-, intra- and postoperative phases, and concerned the
      rationale use and availability of specific monitoring systems, and indications
      for invasive procedures and use of drugs, fluids and blood products. RESULTS:
      There were 162 (64.8%) responders. Seventy-five percent believed that early
      tracheal intubation within the emergency room was necessary, while 25% postponed
      it to the operating room. Basic monitoring was defined as essential by all
      responders, 147 (90.7%) considered invasive arterial pressure monitoring to be
      essential. Fifty-seven (84%) anaesthetists working in hospitals without
      neurosurgical facilities would have transferred the patient after splenectomy.
      Prophylactic hyperventilation was frequently used (36%). Sixty-eight percent of
      responders would have preferred in intracranial pressure monitoring inserted
      before laparotomy, but only 35% actually had this possibility. In case of acute
      intraoperative arterial hypotension after splenectomy, 54% of the responders
      advocated the use of blood or blood products to optimize peripheral oxygen
      transport. CONCLUSIONS: More widespread knowledge of certain areas of severe head
      trauma management such as early tracheal intubation, avoidance of prophylactic
      hyperventilation, adequate invasive monitoring, appropriate use of blood
      products, and timing of transfer to hospitals with neurosurgical facilities is
      needed.

PMID- 15852998
TI  - A comparison of propofol and sevoflurane anaesthesia for percutaneous trigeminal
      ganglion compression.

PMID- 15852999
TI  - Failed spinal anaesthesia after intrathecal chemotherapy.

PMID- 15853000
TI  - Intracerebroventricular and intrathecal injectate spread in rats.

PMID- 15853001
TI  - Perioperative sonoclot analysis in patients given flurbiprofen.

PMID- 15853002
TI  - Difficult airway in an obese patient managed with the ProSeal laryngeal mask
      airway.

PMID- 15853003
TI  - [The place of laparoscopic-assisted radical vaginal hysterectomy in surgical
      treatment of cervical cancer].
AB  - OBJECTIVES: to resume the surgical technique of laparoscopic assisted radical
      vaginal hysterectomy (LARVH) and to show preliminary results of the patients'
      treatment with this method. MATERIAL AND METHODS: in a period of six months
      (16.06.04-16.12.04) in Oncogynecological Clinic, Medical University--Pleven eight
      patients with cervical cancer were performed LARVH on and six--laparoscopic
      pelvic lymph node dissection. RESULTS AND DISCUSSION: LARVH has three steps-
      laparoscopic part, vaginal part and laparoscopic inspection. It is an anatomic
      surgical technique which is assosiated with lower blood lose because of the
      several time enlargement of the operative field by videolaparoscope and the
      profilactic coagulation to even smallest blood vessels. LARVH is a new method in
      surgical treatment of early stage cervical cancer.

PMID- 15853004
TI  - [Primary peritoneal carcinoma: a report of two cases and a review of the
      literature].
AB  - Primary serous peritoneal carcinoma (PSPC) is rare tumor histologically identical
      to epithelial ovarian carcinoma (EOC); it is differentiated from EOC based on the
      extent of gross ovarian involvement and microscopic invasion of the cortex. When
      this tumor involves the extraovarian peritoneum significantly and the ovarian
      surface minimally or not at all, it is generally considered to be of peritoneal
      origin. We report macroscopical and histopathological findings of 2 cases of PPC,
      which were diagnosed, in our Department. Total abdominal hysterectomy, bilateral
      salpingo-oophorectomy and omentectomy were performed in 2 patients. PPC is a rare
      tumor currently managed in the same way as ovarian cancer. Primary debulking
      surgery and chemotherapy represent the cornerstones of treatment. Considering the
      limited number of patients with PPC, no definitive conclusion can be drawn
      concerning the prognostic factors for survival.

PMID- 15853005
TI  - [Ovarian tumours--accuracy of frozen section diagnosis].
AB  - A retrospective study of 450 ovarian biopsy results were examined for the period
      of 1998 till 2004 to evaluate the accuracy of frozen section diagnosis. In
      addition to this we performed a review of the literature for all previous studies
      in this field in order to study the accuracy rates of the different clinics
      throughout the world. The histhopathological results of the frozen section
      diagnosis were equal with the diagnosis of the paraffin blocks in 90%. The
      sensitivity rates for benign, malignant and borderline tumours, were 96%, 84% and
      60% respectively. We had 10 patients (2,1%) false-positive results
      (overdiagnosed) and 26 (5,2%) false-negative results (underdiagnosed) in frozen
      section examinations. Frozen section examination of mucinous tumours showed
      hogher underdiagnosis--18%. The review of the literature showed that there is no
      significant difference in accuracy rates of frozen section diagnosis for benign
      and malignant ovarian tumours in relation with time. We found low accuracy rates
      for borderline tumours which was similar with most of the foreign publications.
      However the accuracy of the frozen section diagnosis is bettering with the time.
      As a result of this we conclude that the accuracy rates of the frozen section
      diagnosis for evaluation of the malignant and benign tumours is quite enough for
      correct diagnosis. Since accuracy rates for borderline ovarian tumours are low we
      have to take care and attention of improvement in this field.

PMID- 15853006
TI  - [Gynecological laparscopy, endometriosis and sterility].
AB  - The authors presented the importance of the gynecological laparoscopy for
      diagnosis of the external genital endometriosis in its different forms. In the
      last 20 years, it was seen that laparoscopy is not only the basic method for
      diagnostics but also for the surgical treatment of the endometriosis. Thirty to
      fifty percent of the females with endometriosis in reproductive age have
      available sterility. The authors presented the cases, which have been
      laparoscopically proven for endometriosis and sterility for 7 years' period in
      Gynecological clinic in MBAL-Pleven and the results from the treatment with
      analog of the Gonadoliberins (Zoladex).

PMID- 15853007
TI  - [Results of diagnostic hysteroscopy in a 7-year period in the gynecological
      clinic of "UMBAL-Pleven"].
AB  - The aim of the authors is to show the data for the reception diagnosis, age,
      histological results and the conduct after the performed diagnostic
      hysteroscopies in Gynecological clinic of UMBAL-Pleven. For the fulfillment of
      this aim was made a prospective study for 7 years' period: from 01/01/1997 to
      31/01/2003. The objects of observation were 74 women of age from 16 to 65 years,
      with performed hysteroscopies for gynecologic complaints. There were performed 74
      diagnostic hysteroscopies for the studied period. The hysteroscopic findings were
      20 cases with endometrial polyposis, 14--submucosal myoamatic nodes, deforming
      the uterine cavity, 4--cervical polyp, 19--increased endometrium, 9--Asherman
      syndrome, 1--bicomous uterus, 1--a suspected section for endometrial carcinoma
      and 6 cases without pathologic findings. There were performed 59 trial abrasions
      and the removed materials were sent for histological examination The performed
      comparative analysis between the hysteroscopic presentation and histological
      findings showed a coincidence of the diagnosis. It was made the conclusion, that
      the hysteroscopy is an easy, accessible and inexpensive diagnostic method, which
      must take its place as one of the basic contemporary diagnostic methods in
      gynecology.

PMID- 15853008
TI  - [Reference values range of the fetal oxygen saturation and its dispersal during
      labor without cardiotocographic evidence for fetal distress].
AB  - The objective of this study is to establish the reference values range of the
      fetal oxygen saturation during the first and the second period of labor and their
      dispersal according to the extent of cervical dillatation in cases with normal
      FHR--absence of fetal hypoxia and asphyxia of the newborn. MATERIAL AND METHODS:
      This is a prospective study which involves 94 women with normal FHR. All of the
      newborns are with umbilical artery pH values greater than 7.15 and 5 min Apgar
      score greater than 7; there was no necessity for any reanimation procedures,
      assisted ventilation or intensive care treatment. The fetal oxygen saturation
      (SpO2) is monitored by fetal pulseoxymeter Nellcor N 400, fetal sensors FS - 14.
      Cardiotocographic monitoring is carried out simultaneously. Blood is obtained
      from the fetal scalp during labor for blood gas and pH analysis, and umbilical
      artery pH as well as the Apgar score of the newborn are determined. RESULTS: The
      average monitoring time during the first period of labor is 107.19+/-29.49 min.
      with reliability of the recordings 86.54+/-6.10%. The average monitoring time for
      the second period of labor is 36.72+/-8.31 min. with reliability of the
      recordings 75.42 +/-9.61%. The mean SpO2 values are 48.71+/-5.52% during the
      first period and 47.30+/-4.62% during the second period of labor. The reference
      SpO2 values ranging between the 25-th and 75-th percentile in fetuses with normal
      FHR are 46-52 % for the first and 44-50 % for the second period. The results for
      fetal SpO2 during the different stages of cervical dillatation are as follows:
      for 4-5 cm - 49.49+/-5.12%, for 6-7 cm - 48.76+/-5.42%, for 8-9 cm - 48.39+/
      5.49%. CONCLUSIONS: The fetal SpO2 dispersal during cervical dillatation of 4-5,
      6-7 and 8-9cm accordingly demonstrates a nonsignificant decrease of SpO2 for the
      different groups (p>0.05). The fetal SpO2 dispersal between the first and the
      second period of labor also demonstrates decrease of SpO2 values and shows a
      minor statistically significant difference (p < 0.05 - Repeated measures ANOVA),
      which is considered to be within the normal range and does not reflect on the
      newborn's well-being.

PMID- 15853009
TI  - [Ultrasound screening for Down syndrome and other chromosomal abnormalities by
      fetal nuchal translucency measurement between 11-14 weeks of gestation].
AB  - AIM: To assess the feasibility of nuchal translucency [NT] measurement as a
      screening tool for Down syndrome [DS] and other chromosomal anomalies [ChA]
      between 11-14 weeks of gestation [w.g.]. MATERIALS AND METHODS: A longitudinal
      prospective follow up study was carried out at a tertiary referral center
      including 408 singleton pregnancies between 11+0 and 14+0 w.g. Three experienced
      sonographers performed transabdominal and/or transvaginal scans using high
      resolution ultrasound equipment. The ultrasound examinations included assessment
      of fetal number and viability, NT measurement and fetal anatomy survey. Down
      syndrome [DS] risk was calculated using the specialized computer program provided
      by the Fetal Medicine Foundation [FMF], UK. In cases of estimated DS risk > or =
      1:300 invasive prenatal diagnosis was offered--chorionic villus sampling [CVS]
      between 11-14 w.g. or amniocentesis [AC] after 15 w. g., as well as follow-up
      scans including fetal echocardiography. The samples were tested by cytogenetic
      analysis, DNA analysis and/or FISH. When chromosomal fetal abnormality was
      detected termination of pregnancy was an option. Pregnancy outcome was
      ascertained from hospital records, referring physicians or the patients
      themselves. RESULTS: 108 (26%) out of the 408 women were ?35 years and 300 (74%)-
      below that age. A total number of 9 fetal chromosomal anomalies [ChA] were found
      including 6 cases with DS, 2--with trisomy 18 [T18] and 1--with Turner syndrome.
      The overall sensitivity for DS was 66.7% for a false-positive rate [FPR] of
      13.4%. The figures for all ChA were 77.7% and 12.8%, respectively. All three
      cases of ChA other than DS were in the screen-positive group. The overall
      sensitivity and FPR for ChA for patients > or = 35 years was 80% and 35%, while
      for patients < 35 years it was 75% and 5.1 %, respectively. Diagnostic invasive
      procedures were performed in 50 out of 58 screen-positive cases, including 7 of
      the cases with ChA. In all 7 cases with prenatal diagnosis of fetal ChA the
      parents chose to terminate the pregnancy. CONCLUSIONS: First trimester DS
      screening by NT measurement has high sensitivity and specificity. Screening for
      other chromosomal abnormalities missed by second trimester biochemical serum
      tests is also possible. Invasive prenatal diagnosis is performed at an early
      gestational age when termination of affected pregnancies by D&C is still an
      option. Other important advantages are the possibility of screening for ChA in
      multiple gestations, as well as early diagnosis of major fetal anomalies.

PMID- 15853010
TI  - [Link between the state of vaginal flora and the development of uroinfection
      during pregnancy].
AB  - One hundred and forty urines and vaginal secretions from pregnant women were
      investigated. Significant account of microorganisms in urine was found in 12
      cases/8.5%/. In the group I/N normal vaginal flora/ in 3.2%, in the group II/I
      intermediate vaginal flora/ in 8.1%, in the group III/BV/ in 20% of the cases.
      The high-degree vaginal colonization with uropathogens endangers the women with
      development of ascendant uroinfection during pregnancy.

PMID- 15853011
TI  - [Lymphocyte populations and subpopulations in peripheral blood of pregnant women
      with pre-eclampsia].
AB  - AIM: To investigate the changes of lymphocyte populations and subpopulations in
      peripheral blood of pregnant women suffering preeclampsia. MATERIAL AND METHODS:
      By means of flowcytometry the following lymphocyte populations and subpopulations
      were determined in peripheral blood of 37 pregnant women, of whom 12 had
      preeclampsia and 25 had normal pregnancy pespectively: Total lymphocyte count
      CD19+ (B-lymphocytes), CD2+ (Total T-lymphocytes), CD3+ (Immunocompetent T
      lymphocytes) CD3+CD4+ (T-helpers), CD3+CD8+ (Suppressor-cytoxic T-lymphocytes),
      CD4+/CD8+ ratio, Lymphocyte subpopulations with predominant killer activity: CD8
      CD56+, CD8+CD56+ and activated immunocompetent T-lymphocytes (CD3+HLADR+).
      RESULTS: In patients with preeclampsia a T-helper increase and relative T
      suppressor cytotoxic decrease was found. A significant increase of activated
      immunocompetent T-lymphocyte was found, compared to the total increase of
      immunocompetent T cell. No significant difference between cytotoxic cell with MHC
      unrestrained function (CD8-CD56+) and cell with MHC restrained cytotoxic function
      (CD8+CD56+) was found. CONCLUSIONS: In pregnant women with preeclampsia the main
      lymphocyte populations and the immunocompetent T-lymphocytes are increased. The
      raised level of T-lymphocytes is found as a result of the substantial
      quantitative changes of T-helper cells an increase of CD4+/CD8+ ratio is
      prominent, which is a proof of the activated immune potential in pregnant women
      with preeclampsia with the dominant influence of T-helper subpopulations.

PMID- 15853012
TI  - [Uterine endosonography with sterile serum infusion in infertile women].
AB  - Infusion of sterile serum in the uterine cavity during ultrasound examination is
      useful for investigation bout polyps, submucous myoma, adhesion and anatomical
      malformation. Examination of the patients with ultrasound is suitable to be with
      medicine in the infusion, menometrorrhagia sterility, all changes in the
      endometrium. CONTRAINDICATIONS: genital infection, pregnancy, neoplasma of cavum
      uteri. TECHNIQUES: investigation was between 7th and 12th day of the cycle. We
      used insemination catheter to put in the cervical canal. There is a syringe with
      infusion on the other end. The speculum was took of the vagina and put on the
      transducer. We performed examination of the uterus in the different scans. When
      the infusion was fulfilled the avum uteri we observed different findings. 24
      patients with sterility were passed for ultrasound examination with sterile serum
      for the period of 1 year (2003--2004). We diagnosed normal cavum uteri thiken
      endometrium, endometrial polyp, submucous myoma amd malformation uteri.

PMID- 15853013
TI  - [Upper extremity gangrene in an infant of a diabetic mother, presenting at
      birth].
AB  - In utero gangrene of an extremity because of an arterial thrombosis is rare. More
      than 20% of the reported cases concern infants of diabetic mothers (IDM) with
      poor control of diabetes. Changes in coagulation related to deviation of clotting
      factors and low plasminogen activity may be the cause. We report a case of an IDM
      who presented at birth with upper extremity gangrene. The Dopplersonography has
      shown missing pulsations and thrombosis of a. brachialis sin, which was confirmed
      after amputation of the arm on the 5th day. The postoperative period was
      complicated by septicaemia, necrotising enterocolitis and disseminated intravasal
      coagulation resulting in the baby's death 10 days after birth.

PMID- 15853014
TI  - [Localization of leiomyoma with respect to the placenta--factor for complications
      during pregnancy?].
AB  - We are presenting two cases of pregnant women with leiomyoma of the uterus,
      diagnosed antepartum. In both cases the patients were admitted on an emergency
      basis due to premature uterine contractions. In both cases preterm hemorrhage and
      fetal malpresentations were observed. The complications of pregnancy in both of
      the cases were primarily based on the location of the leiomyoma with respect to
      the placenta--intramural or submucosal disposition of the leiomyoma,
      retroplacentarily situated.

PMID- 15853015
TI  - [Weak D (Du) phenotype and pregnancy].

PMID- 15853016
TI  - [A case of abdominal pregnancy in 16-th gestational week].
AB  - The authors report a rare case of an abdominal pregnancy in 16-th gestational
      week. The diagnostic difficulties and management of the abdominal pregnancy are
      discussed.

PMID- 15853017
TI  - Correlation of conventional and liquid-based cytology and their meaning in
      management of precancerous cervical lesions.
AB  - AIM: Introduction of efficiency of liquid-based citoscreen cytology METHOD:
      Conventional cytology with Papanicolaou method and comparison with novel cytology
      liquid-based method in women with histological findings associated to Human
      Papilloma Virus praecancerous lesions for "gold standard" method. RESULTS: 100
      women with praecancerous cervical lesions were included in the study. In all of
      the women, biopsy and endocervical curettage were made, and histological results
      were taken as a "gold standard". From the histology: LSIL was found in 64 women
      (64%) and HSIL in 36 women (36%). In LSIL, in 8 women the lesions are associated
      with existence of HPV or with coilocitic atipya and the other 56 women were with
      CIN 1. In group with HSIL, in 26 women was found CIN 2, 6 women were with CIN 3
      and 4 women with CIS. In all women from both groups, conventional PAP and LBC
      cytoscreen were made. The results from conventional PAP were adequate in 42 women
      (42%), sub diagnosis in 34 (34%), over diagnosis in 10 (10%) and false-negative
      in 14 (14%). The results from LBC cytoscreen were adequate in 56 (56%), sub
      diagnosis in 22 (22%), over diagnosis in 16 (16%) and false-negative in 6 (6%).
      Sensitivity for PAP test is 84% and for LBC 94%. CONCLUSION: LBC cytoscreen
      method is better than the conventional PAP test in detection of the cervical
      epithlial abnormalities.

PMID- 15853018
TI  - [Risk factors for fetal macrosomia].
AB  - AIM: To determine the influence of some of the risk factors on fetal macrosomia.
      MATERIALS AND METHODS: A retrospective study was provided at the Department of
      Obstetrics and Gynecology, Medical University, Pleven, from January, 1, 2001 to
      December, 31, 2002 over 625 deliveries: 225 cases of fetal macrosomia--fetal
      birth weight (FBW) more than 4000 g and/or over 90. percentile (macrosomic group-
      MG) and 400 cases of singleton term newborns--with FBW between 10. and 90.
      percentile (nonmacrosomic group--NMG). Analysis included influence of: maternal
      age, height, prepregnant weight, BMI, weight gain and weight before delivery,
      previous delivery of macrosomic infant, maternal diabetes mellitus, fetal sex and
      gestational age. RESULTS: A comparative analysis of data for both of groups was
      performed. It was found significant correlation (p = 0.001) for influence of
      maternal age (r = 0.34); height (r = 0.33); prepregnant weight (r = 0.42); BMI (r
      = 0.32); weight before delivery (r = 0.49); weight gain (r = 0.34); previous
      delivery of macrosomic infant (r = 0.41); maternal diabetes mellitus (r = 0.54);
      fetal sex (r = 0.37) and gestational age (r = 0.39). Correlations are different
      in both of groups. CONCLUSION: Positive correlations between analysed factors and
      delivering of macrosomic infants and differences in both of groups suggest that
      analysed factors can't explain completely fetal macrosomia.

PMID- 15853019
TI  - [The place of the planned cesarean section in women with breech presentation].
AB  - We studied retrospectively the delivery of 202 pregnant women with foetus in
      breech presentation. Caesarian deliveries have had 79.2% from primiparas and
      31.3% from multiparas. Planned caesarian deliveries have been performed to two
      thirds (63.7%) from the primiparas (n = 135). In the context of cotemporary
      literature and practice we consider, that we do not make enough "trial of vaginal
      labour" for women with breech presentation of the foetus and we think, that
      caesarian delivery frequency in these cases is too high.

PMID- 15853020
TI  - [Intraoperative lymphatic mapping and sentinel lymph node dissection in cervical
      uterine cancer].
AB  - Regional lymph node involvement is the most important prognostic indicator in
      patients with solid tumors. Conventional lymph node dissection has not been shown
      to affect survical and is often associated with considerable morbidity.
      Intraoperative lymphatic mapping and sentinel lymph node dissection were
      therefore designed as a minimally invesive alternative to routine elective lymph
      node dissection in patients with primary cutaneous melanoma. This study examined
      whether intraoperative lympatic mapping and sentinel lymph node dissection were
      accurate in staging patients with cervical cancer.

PMID- 15853021
TI  - [Chemoimmunoterapy in combination with radiotherapy for treatment of stage III B
      cervical cancer].
AB  - We wanted to examine the tolerability and the toxicity of the chemoimmunotherapy
      in combination with radiotherapy in patients with stage III B cervical cancer.
      Sixteen patients were selected for examination and the experience of the
      Gynecological Cancer Center in Sidney was summarized as well. We used cisplatin
      in dose from 10 to 20 mg/m2 intravenously weekly, 5-Fluoruracil/5 Fu/500 mg/m2-
      24 hours infusion, weekly, interferon-alpha--2a 3MU subcutaneously for 3 days
      course weekly and 13 cis-retinoic acid 0.5 mg/kg daily by month together with 8
      weeks period of radiotherapy after the end of the radiotherapy these medicaments
      were given for another 4 weeks. According to the dose of the cisplatin
      medicaments we divided the patients into 3 groups--first group--6 patients with
      dose to 10 mg/m2 cisplatin, second group--6 patients to 15 mg/m2 cisplatin, third
      group 4 patients with dose to 20 mg/m2 cisplatin. The patients from the first and
      second group tolerated the cisplatin. In the third group--4 patients had
      leucopenia. After the end of chemoimmunotherapy and the patients recovered from
      the toxicity, they prolonged with radiotherapy. In conclusion from our small
      experience the cisplatin--15 mg/m2, 5-Fu-500 mg/m2 weekly, interferon alpha--2a
      3MU subcutaneously for 3 days course weekly and 13-cis-retinoic acid 0.5 mg/kg
      daily in combination with radiotherapy for stage III B cervical cancer we can say
      that and the dose is tolerated extremely well. The leucopenia is the dose
      limiting toxicity for this group of patients. The survival rate will be followed.
      The first results show better survival rate for this group of patients.

PMID- 15853022
TI  - [Proliferation of villous trophoblast and stroma in normal and pathologic
      pregnancies (preeclampsia)].
AB  - Pregnancies, complicated with preeclampsia, present with intrauterine growth
      retardation of the fetus and small (in size and weight) placentas. The present
      study aims at establishing the expression of proliferative nuclear antigen Ki-67
      in the villous trophoblast and stroma, and to compare the results between study
      (preeclamptic cases n = 30) and control (normal n = 30) groups. The number of Ki
      67 positive nuclei both in the preeclamptic trophoblast and stroma significantly
      increases those of the controls. Our results show that the defect in the
      development of the placenta in preeclampsia is not associated with low
      proliferative potential.

PMID- 15853023
TI  - [Gynecological laparoscopy and treatment of ectopic pregnancy].
AB  - The aim of the present study is to show the advantages of the gynecologic
      laparoscopy for the diagnosis and treatment of the intact tubal pregnancy. For
      the fulfillment of this aim was made a prospective study for 5 years' period of
      the patients with diagnosis "Ectopic pregnancy", treated in Gynecological clinic
      of UMBAL-Pleven. The objects of observation were 33 women with diagnosis: "Intact
      ectopic pregnancy". Methotrexate was used by plan for 6 patients, in 7 patients
      was made laparotomy, and in 20 patients--gynecological laparoscopy. From the
      performed 20 gynecological laparoscopy, 16 women were recovered laparoscopically,
      in 14 of which was made partial salpingectomy, and in 2--milking. In one of the
      last two patients was injected Methotrexate in the bed of the gestational bag. In
      4 women was necessary laparotomy, because of impossibility of performing of
      laparoscopic surgery. The authors emphasized the advantages of the gynecological
      laparoscopy for precise diagnosis and contemporary treatment of the intact
      ectopic pregnancy.

PMID- 15853024
TI  - [Correlation between receptive wall analysis of benign ovarial cysts and their
      clinical conduct].
AB  - The biological behaviour (conduct) of benign ovarial cysts is interesting due to
      their comparatively high frequency of appearance and clinical manifestation.
      (During the last five years their frequency is between 62%-65% of the
      gynaecological surgical interventions). With this current survey the authors try
      to set up a target for research study of the wall receptive status of benign
      ovarial cysts. This study should be treated as a start up point rendering a
      prognosis for their eventual biological development. MATERIALS AND METHODS: An
      immunohistochemical survey was carried on with 50 patients who have already
      reached the surgical treatment in retrospective order for the period 2001-2003
      (three years' period). The survey search is in direction receptive analysis of
      Estrogene /E2/ and Progesterone /P/ wall receptor in the ovarial cyst. A
      perspective observation was also carried on (control group of 50 cases) of
      hormonal-gestagene treatment of the benign ovarial cystogenesis. It appears to be
      the necessary prove material for hormonal receptors' participation in the cyst
      wall as an active factor for its development and involution. RESULTS: In the
      basic group /surgical treatment/ it was stated: In 39 patients--E2/-/, P/-/; in 4
      patients--E2/+/, P/+/ In 5 patients--E2/+/, P/-/; in 2 patients--E2/-/, P/+/
      CONCLUSION: The executed retrospective analysis demonstrates statistical
      importance in receptor competency lack in the wall of benign ovarial cysts as the
      probable grounds for them not being influenced during the conservative treatment
      method. This method led to the surgical elimination of the cyst. The statistical
      reliability, connected with the receptor E2 participation in the therapeutic
      behaviour of the benign ovarial cysts, is not stated. The final conclusions
      acquired from the executed research work would be a discussion issue after the
      correlative aspects in the prospective group are surveyed. The benign ovarial
      cysts' hormonal profile would be taken into consideration also.

PMID- 15853025
TI  - [First facioscapulohumeral muscular dystrophy prenatal diagnosis in a Bulgarian
      family].
AB  - Facioscapulohumeral muscular dystrophy (FSHD) is the third most common myopathy.
      It is characterized by progressive descendent involvement of facial, shoulder
      girdle, truncal and lower extremities muscles. FSHD locus was mapped on the
      terminal part of the long arm of chromosome 4 (4q35). The disease is caused by a
      deletion of an integral number of tandem D4Z4 repeats and dimension of the
      pathological fragments < or = 38kb. Prenatal diagnosis of FSHD is possible but it
      is potentially difficult because of the big amount and high quality of DNA
      required. Hereby we describe the first prenatal tests performed for a Bulgarian
      family.

PMID- 15853026
TI  - [Fetal ovarian cyst--possible modalities for subsequent follow up and
      management].
AB  - We present a case report of a fetal ovarian cyst (d - 40/50 MM), which was
      diagnosed at 30 weeks of gestation [w.g.] and removed by laparotomy after a
      Cesarean section performed at term. The possible modalities for subsequent follow
      up and management are discussed.

PMID- 15853027
TI  - [Amyloid-producing leiomyoma of the womb--a complete morphological study and
      possible etiology].
AB  - Case study of a 41 year old woman with tumor-related amyloidosis in a singular
      intramural leiomyoma of the uterine corpus. The tumor has been thoroughly revised
      with electron microscopy and underwent a histological, histochemical, and
      imunohistochemical studies. A hypothesis of its origin has been suggested. To our
      knowledge, this is the first documented case of amyloid-producing leiomyoma.

PMID- 15853028
TI  - [Microglandular endocervical hyperplasia and endocervical adenocacinoma in
      pregnant--description of two cases].
AB  - Two clinically identical cases of young, pregnant women, presented with
      exocervical polypoid masses are described. Because of beginning delivery in both
      cases, the diagnoses are made on frozen sections. In the first case histological
      examination reveals microglandular endocervical hyperplasia. A successful
      delivery by caesarian section and no more operations is performed. In the second
      case, an endocervical adenocarcinoma is diagnosed and after a successful delivery
      by caesarian section, a laparohysterectomy with bilateral adnexectomy and lymph
      node dissection is performed. Detailed histological examination of the
      endocervical neoplasm discloses a well differentiated papillary villoglandular
      adenocarcinoma, containing minor elements of more aggressive serous carcinoma,
      which may adversely affect the outcome. Three consequent recurrences are found in
      this patient for a period of 5 years and 3 months after the operation.

PMID- 15853029
TI  - [Choriocarcinoma of the uterine tube--a rare localization].

PMID- 15853030
TI  - The right plan at the riqht time.

PMID- 15853031
TI  - Physicians' Plan for a healthy Minnesota. The MMA proposal for health care
      reform. The report of the Minnesota Medical Association Health Care Reform Task
      Force.
AB  - The health care system in the United States, according to some, is on the verge
      of imploding. The rapidly rising cost of services is causing more and more
      Minnesotans to forego needed care. At the same time, the increasing costs are
      placing additional pressure on families, businesses, and state and local
      government budgets. The Minnesota Medical Association's (MMA) Health Care Reform
      Task Force has proposed a bold new approach that seeks to ensure affordable
      health care for all Minnesotans. The proposal is a roadmap to provide all
      Minnesotans with affordable insurance for essential health care services. In
      creating this plan, the task force strove to achieve three common reform goals:
      expand access to care, improve quality, and control costs. To achieve those ends,
      it has proposed a model built on four key features: (1) A strong public health
      system, (2) A reformed insurance market that delivers universal coverage, (3) A
      reformed health care delivery market that creates incentives for increasing
      value, (4) Systems that fully support the delivery of high-quality care. The task
      force believes that these elements will provide the foundation for a system that
      serves everyone and allows Minnesotans to purchase better health care at a
      relatively lower price. Why health care reform again? The average annual cost of
      health care for an average Minnesota household is about 11,000 dollars--an amount
      that's projected to double by 2010, if current trends continue. Real wages are
      not growing fast enough to absorb such cost increases. If unabated, these trends
      portend a reduction in access to and quality of care, and a heavier economic
      burden on individuals, employers, and the government. Furthermore, Minnesota and
      the United States are not getting the best value for their health care dollars.
      The United States spends 50 percent more per capita than any other country on
      health care but lags far behind other countries in the health measures of its
      population.

PMID- 15853032
TI  - The growing challenge of Medicare.

PMID- 15853033
TI  - A philosophy in PHD.

PMID- 15853034
TI  - No place like home: telemonitoring can improve home care.
AB  - Effective use of telemonitoring equipment can reduce costs of providing home
      health care and increase revenues enough to ensure the fiscal health of this
      industry segment. Using telemonitoring as a basis, a home health agency can
      develop a disease management program, making itself more attractive to managed
      care organizations. Telemonitoring offers home health agencies a means to partner
      with hospitals to help reduce length of stay and recurrent hospitalizations of
      patients with chronic illness.

PMID- 15853035
TI  - Employer-directed marketing: a boon for hospitals.
AB  - Frustrated by their inability to measure the financial contribution of
      traditional advertising, hospital CFOs are turning to employer-focused marketing
      initiatives to enhance volume and payer mix.

PMID- 15853036
TI  - Top 10 questions for rural, community hospital CFOs.
AB  - Want an easier way to keep tabs on your revenue cycle? CFOs and business managers
      at rural, community hospitals will find these 10 questions handy when developing
      action plans to correct underperforming areas.

PMID- 15853037
TI  - Containing costs in the ED.
AB  - Slow patient throughput doesn't have to be the norm in your ED. In this article,
      leaders from several hospitals discuss strategies they have used to improve
      patient flow, reduce patient wait times, decrease ambulance diversion hours, and
      improve resource use.

PMID- 15853038
TI  - HFMA focus: financial billing policies for the uninsured.

PMID- 15853039
TI  - Strategic supply cost management: physician preference without deference.
AB  - Strategic supply chain management differs from traditional supply chain
      management in that it leaves nothing to chance: It takes into account physician
      preference in product selection and pricing. It does not allow vendors to bypass
      supply chain leaders. Its leaders require a broad understanding of strategic,
      financial, and clinical issues. Its leaders are accountable for maintaining
      control over supply costs across the board.

PMID- 15853040
TI  - Taking a new look at the hosted applications model.
AB  - Deciding whether to adopt a hosted applications model for your organization?
      Advantages--rapid time to value, no hardware and software maintenance
      responsibilities, reduced IT staff support burden. Disadvantages--reliance on the
      Internet to deliver applications, concerns about security, and limited
      customization options with some vendors.

PMID- 15853041
TI  - Harnessing technology to redesign labor cost management reports.
AB  - Over the past two decades, the difficult hospital productivity puzzle of how to
      manage labor costs has evolved into a far more complex multidimensional Rubik's
      Cube. The complexity has been compounded by the creation of massive databases to
      capture all types of hospital information. The challenge is to make use of
      advances in IT to create more meaningful labor cost management tools.

PMID- 15853042
TI  - Understanding statements now a virtual cinch.
AB  - With a click of the mouse, some patients are accessing and paying their hospital
      bills online. Novant Health revamped its patient billing process so it's easier
      to understand and use. Developing a clear, concise billing statement and then
      implementing an online bill presentment and payment system resulted in improved
      customer relations, fewer payment processing errors, and faster receipt of
      payment.

PMID- 15853043
TI  - Northwest synergy: a lesson in effective collaboration.
AB  - Collaboration can be the most effective way to preserve the financial viability
      of providers and service lines in the same competitive market. When pursuing a
      large-scale collaboration, it's best to start small, with a single specific
      service area that can act as a testing ground for working out organizational,
      cultural, and financial issues. Organizational, cultural, and financial issues
      are best dealt with by focusing the collaborative effort within an entity that
      has a separate organizational structure.

PMID- 15853044
TI  - Analyzing your hospital's labor productivity.

PMID- 15853045
TI  - Cost management and leadership: the ethical high ground.

PMID- 15853046
TI  - Not another gizmo!

PMID- 15853047
TI  - Annexing the neighbor's backyard: increasing area service.

PMID- 15853048
TI  - Controlling supply costs key to profitability for spinal fusion.

PMID- 15853049
TI  - History in the making.

PMID- 15853050
TI  - The business of caring.

PMID- 15853051
TI  - A labour of love.
AB  - Dame Lorna Muirhead retired recently after 40 years in midwifery and more than
      seven years as president of the Royal College of Midwives. She has seen many
      changes--not all of which she agrees with. Her life's work has been at the
      bedside and championing the cause of midwives

PMID- 15853052
TI  - Going green.
AB  - While citizens are being encouraged to become 'green' and recycle household and
      garden waste, the NHS is lagging far behind. Clinical waste has to be disposed of
      in a safe way, much 'domestic' waste could be recycled and save trusts money--as
      some hospitals in the United States have found.

PMID- 15853053
TI  - Crossed wires.

PMID- 15853054
TI  - Look and learn.

PMID- 15853055
TI  - Using a competency based approach in nurse education.
AB  - This article examines the development of the competency based approach to
      assessment in practice within pre-registration nursing. An historical perspective
      to the approach is given, including brief descriptions of the different models
      that have been used in nurse training and how these relate to the current system
      of nurse education. The approach is examined in relation to government,
      professional and educational requirements. Implications for practice are
      discussed, taking into consideration staffing levels, training and availability
      of mentors and assessors, and the impact these have on nurse training.

PMID- 15853056
TI  - Assessing motivation and readiness to alter lifestyle behaviour.
AB  - The aim of this article, the second in the health promotion series, is to
      highlight the importance of assessing clients' motivation and readiness to
      change, and to offer advice on how to achieve this.

PMID- 15853057
TI  - Haemodynamic monitoring: arterial catheters.
AB  - The arterial catheter is one of the most common monitoring tools available in the
      intensive care unit. However, as an invasive device it has the potential to cause
      complications, especially when managed by inexperienced staff. When successfully
      managed, it can facilitate the high-level care needed by the critically ill
      patient.

PMID- 15853058
TI  - Grief and bereavement.
AB  - As a nurse working in a busy 18-bed medical ward, I have encountered many dying
      patients, and have witnessed the grief which death causes family members and
      friends. This article discussed how impending loss and bereavement affect people,
      and provided an insightful explanation of how people react to the death of a
      loved one and the reasons.

PMID- 15853060
TI  - Solve it.

PMID- 15853059
TI  - Taking the fight to the streets.

PMID- 15853061
TI  - Keep in touch.

PMID- 15853062
TI  - [The treatment of the disease "hypertonia" based on the new recommendations].
AB  - Hypertonia is a widespread disease among the population, and one of the most
      important reasons behind the morbidity and mortality of cardiovascular diseases.
      In the past few years, recommendations from the American (JNC 7), the European
      (ESH/ESC 2003) and the Hungarian Hypertonia Associations have been published. The
      international and domestic recommendations are similar in that they all state
      that normal and optimal blood pressure is 120/80 Hgmm. The lower limit of
      hypertonia is specified as 140/90 Hgmm. The reduction of risks is an absolute
      priority in the treatment of hypertonia. Before starting the administration of
      medicines, the patient's risk category is identified and a target blood pressure
      is specified. The treatment strategy is then set up. The recommendations deal in
      detail with the first choice, the fixed and not fixed combinations of medicines
      to be administered. All three recommendations pay special attention to the
      determination of the indicators of preventing thrombocyte aggregation and statin
      treatments.

PMID- 15853063
TI  - [Squamous papilloma of the esophagus. Clinical and pathological observations
      based on 172 papillomas in 155 patients].
AB  - INTRODUCTION: The papilloma of the oesophagus is a rare disease. The pathogenesis
      and biological features of the disorder are not clearly known. AIMS: The purpose
      of the present paper is to outline the clinical and pathological significance of
      the papilloma of the oesophagus as detected in the authors' endoscopic
      laboratory. METHODS: Endoscopic examinations were carried out with a flexible
      endoscope. The alterations in the oesophagus were removed by biopsy forceps in
      order to perform histological investigations, large-sized ones were removed by
      way of endoscopic mucosectomy. To assess the structure major alterations and
      their circumstances relative to their environment, endoscopic ultrasonography was
      performed, as well. Histological examination was done in formalin-fixed slides
      embedded in paraffin and dyed with hematoxiline eosine. HPV detection was done
      through polymerase chain reaction (PCR). RESULTS: During the 35 years a total of
      59.056 upper panendoscopic examinations were carried out. Planocellular papilloma
      were detected in 155 patients (0.26% of the total number of patients). 85 of the
      patients were female, 70 were male. The vast majority of papilloma cases were
      solitary (142 patients). A minority--13 patients--had multiplex alterations. Most
      often, the papillomas were sessile changes, most often located in the middle and
      upper part of the intrathoracic section of the oesophagus. The probability of the
      papilloma can be established on the basis of the findings of endoscopic
      morphology, as well. This, however, has to be supported by a histological
      examination. In the majority of the cases the papillomas of the oesophagus can be
      removed by endoscopical biopsy forceps, because most often the alterations were
      only a few millimetres in size. Larger papillomas can be removed by way of
      endoscopic mucosectomy. Examining the transformation of papillomas into
      carcinomas, no papilloma was found which directly transformed into a carcinoma.
      Synchronically occurring planocellular carcinoma was found in the oesophagus of
      only 2 out of the 155 patients. During the follow-up examination of patients,
      recurrence of the disease was found only in one patient. The frequency of the
      human papilloma virus in papilloma of the oesophagus: the authors were able to
      detect the presence of HPV by way of PCR technique in 12 out of 26 cases (46.2%).
      With the expectation of 3, they were all viruses with a high risk of cancerous
      transformation. CONCLUSION: The squamous papillomas of the oesophagus are begin
      tumors. Papillomas is not caused by hiatus hernia or reflux oesophagitis. The
      distinct localization of the two different types of alternations also suggests a
      non-reflux oesophagus origin of the papilloma. The reason is that papillomas are
      most often located in the middle and upper part of the intrathoracic section of
      the esophagus--on the other hand, reflux esophagitis is located in the lower
      section. It is now generally accepted that papillomas of the mucous membrane
      covered by multiple planocellular layers are caused by HPV. The identical
      localization of the papillomas and planocellular cancer in the oesophagus refer
      to potentially identical etiology (HPV infection), and it may rarely occur that
      the papillomas wil in fact transform into carcinoma. Papillomas of the esophagus
      is a rare disorder. Its detection is in part important in order to distinguish it
      from planocellular carcinoma (especially carcinoma verrucosum), In part it
      indicated the HPV-infection of the oesophagus, or in HPV-positive cases it may be
      regarded as a precancerous state. For all this, it is important that the
      papilloma should be recognised by way of endoscopic examination, removed and a
      precancerous state should be taken into consideration.

PMID- 15853065
TI  - [The problem of multiple testing and solutions for genome-wide studies].
AB  - The problem of multiple testing and its solutions for genome-wide studies. Even
      if there is no real change, the traditional p = 0.05 can cause 5% of the
      investigated tests being reported significant. Multiple testing corrections have
      been developed to solve this problem. Here the authors describe the one-step
      (Bonferroni), multi-step (step-down and step-up) and graphical methods. However,
      sometimes a correction for multiple testing creates more problems, than it
      solves: the universal null hypothesis is of little interest, the exact number of
      investigations to be adjusted for can not determined and the probability of type
      II error increases. For these reasons the authors suggest not to perform multiple
      testing corrections routinely. The calculation of the false discovery rate is a
      new method for genome-wide studies. Here the p value is substituted by the q
      value, which also shows the level of significance. The q value belonging to a
      measurement is the proportion of false positive measurements when we accept it as
      significant. The authors propose using the q value instead of the p value in
      genome-wide studies.

PMID- 15853064
TI  - [The place of estramustine in the treatment of prostate cancer].
AB  - INTRODUCTION/AIMS: Prostate cancer is a dynamic disease. Androgen ablation is
      palliative, and does not cure advanced prostate cancer. The hormone-sensitive
      cells die, and the hormone-resistant cells come into excess; the disease then
      progresses, which results in a deterioration of the condition of the patient. The
      theoretical basis of the curing strategy is the fact that the prostate tumour
      itself changes during the progression; the molecular determinants of the
      resistance are present in the varying stages of the disease. The treatment of
      advanced prostate cancer remains unsolved; it is a well-known fact that a hormone
      resistant state develops after the primary treatment forms (androgen withdrawal).
      The drug of choice for the secondary treatment is estramustine. This can be
      utilized as monotherapy or in combination. METHODS: In the present study, the
      results of estramustine treatment of 79 patients with advanced prostate cancer
      were evaluated. The preparation, known and clinically applied for more than 20
      years, was studied in 12 centres. RESULTS: The mean prostate-specific antigen
      level improved for 6 months, but rose from the 9th month on. The improvement in
      the subjective condition of the patients paralleled the change in the prostate
      specific antigen level. The shortness of the improvement was a consequence of the
      very high prostate-specific antigen level and the poor general condition.
      CONCLUSIONS: Estramustine administration is recommended when the prostate
      specific antigen level becomes more than doubled following the primary treatment.
      At a starting prostate-specific antigen level of >100 ng/ml, the treatment leads
      to total androgen blockade. If the prostate-specific antigen level has not
      decreased after treatment for 3 months, the secondary strategy is to apply
      chemotherapy.

PMID- 15853066
TI  - [Treatment of urinary tract infections].

PMID- 15853067
TI  - [Commencement address in the 236th academic year].

PMID- 15853068
TI  - Where the waters are rising: a close-up look at the low-lying Malsives, where
      global warming hits the seawall.

PMID- 15853070
TI  - [Creation of a nursing society, the battle for the National Federation of Nursing
      Students). Interview by Helene Delmotte].

PMID- 15853071
TI  - [Laetitia Ricou, laureate nursing student at the Bleustein-Blanchet Foundation.
      Interview by Helene Delmotte].

PMID- 15853072
TI  - [Temporary work, necessary or profitable?].

PMID- 15853073
TI  - [Parents of premature infants: what happens during the first year?].

PMID- 15853074
TI  - [Atherosclerosis: butter on the arteries?].

PMID- 15853075
TI  - [Evolution of transfusion risks in 15 years (1987-2002)].

PMID- 15853076
TI  - [Handwashing].

PMID- 15853077
TI  - [Bladder catheterization].

PMID- 15853079
TI  - [The House of Diabetes and informing and educating about cardiovascular risk].

PMID- 15853080
TI  - [Instruments of past years].

PMID- 15853081
TI  - ["Depression: a disease or bad luck?" Interview by Helene Delmotte].

PMID- 15853082
TI  - [Patient associations and users of the health system].

PMID- 15853083
TI  - [Ezetimibe].

PMID- 15853084
TI  - N-type calcium channel blockers: a call for papers.

PMID- 15853085
TI  - No time limit on Medicare hospice benefit.

PMID- 15853086
TI  - The hospice Medicare benefit and peer review.

PMID- 15853087
TI  - The quality of life of hospice patients: patient and provider perceptions.
AB  - The purposes of this study were to describe the quality of life (QOL) of
      terminally ill patients in a home-based hospice program and to examine the
      relationship between QOL data and patients' symptom distress, ability to
      function, interpersonal communication (support from family and friends), well
      being (their affairs in order), and transcendence (religious comfort/support) as
      recorded in their charts. QOL was measured by the Missoula-Vitas Quality of Life
      Index (MVQOLI), an instrument designed specifically for use with terminally ill
      patients. The study was conducted over a three-year period with 129 terminally
      ill patients enrolled in a home-based hospice program of care. The MVQOLI was
      administered to patients within 20 days of their admission to hospice. A
      retrospective chart review was conducted to determine patients' levels of symptom
      distress, ability to function, social support, whether or not their affairs were
      in order, and religious comfort/support. The mean age of participants in this
      study was 67, with 54.3 percent male and 45.7 percent female. Cancer was the
      primary diagnosis for 92.2 percent of the sample, and 35 percent of these
      patients had a diagnosis of lung cancer. Of the 7.8 percent non-cancer diagnoses,
      five were diagnosed with AIDS, four with chronic obstructive pulmonary disease,
      and one with chronic heart failure. The results of this study revealed positive
      scores on the five dimensions of the MVQOLI QOL scale, indicating that within 20
      days of admission to hospice, patients rated their QOL as good to very good. Data
      obtained from the chart review also indicated that patients did not experience a
      great deal of symptom distress (e.g., pain, nausea, shortness of breath, and
      restlessness). A significant correlation existed between age and QOL; number of
      interventions and pain levels; and marital status, well-being, interpersonal
      relationships, and transcendence. Shortness of breath and well-being were
      significantly correlated with QOL. There was no significant correlation between
      gender, race, or closeness to death and the five dimensions of the MVQOLI and
      chart review assessments.

PMID- 15853088
TI  - Palliative care volunteerism among college students in Canada.
AB  - The goal of Study 1 was to investigate whether young Canadian adults were
      interested in becoming involved in palliative care volunteer work. After reading
      a brief description of what volunteering in a palliative care environment
      typically involves, participants (undergraduate students) were asked to indicate
      whether they would be interested in this kind of volunteer experience and to
      provide a written explanation of their answer. Of the 105 participating students,
      only 39 (37.1 percent) expressed an interest in volunteering, while 66 (62.9
      percent) were not interested. Not surprisingly, the results revealed that
      significantly more females than males were interested in palliative care
      volunteer work (45.9 percent and 25.0 percent, respectively). The most common
      reason students gave for wanting to become a palliative care volunteer was to
      help others; the reason given most often for not wanting to volunteer was that it
      would be too emotionally demanding. It is important to note that prior to taking
      part in this study the majority of the participating students (75.9 percent) did
      not know what palliative care was. The goal of Study 2 was to investigate
      undergraduate students' interest in volunteering in a nursing home, in a
      classroom, and at a food bank. Of the 111 participating students, 74 (66.7
      percent) expressed an interest in volunteering at a food bank and in a nursing
      home, and 89 (80.2 percent) were interested in becoming a classroom volunteer.
      Together, the results of Studies 1 and 2 support the view that young people in
      Canada (especially males) are not interested in becoming involved in the care of
      dying persons. However, the results also indicate that they are very interested
      in volunteering with other populations (e.g., the elderly, school children) and
      in other settings (e.g., food bank).

PMID- 15853089
TI  - Exploratory study on end-of-life issues: barriers to palliative care and advance
      directives.
AB  - BACKGROUND: In the United States, as in most developed countries, death is rarely
      unexpected. It usually occurs in older persons with chronic progressive illnesses
      that often are complicated by infections or exacerbations. Many patients with
      terminal illnesses choose palliative care to relieve symptoms, improve the
      quality of their lives, and strive for a peaceful death. Professionals who serve
      dying patients need to recognize the importance of advance directives as part of
      a patient's decision to forgo curative treatment for palliative care. OBJECTIVES:
      SOLACE (Supporters of Life-Affirming Care at End of Life) is a coalition of
      interdisciplinary professionals in the northern Virginia community dedicated to
      improving end-of-life care. The objectives of the SOLACE survey were to identify
      and describe: 1) professionals' perceptions about barriers related to hospice and
      palliative care, 2) professionals' opinions about barriers related to dying at
      home, 3) professionals' perceptions about barriers related to advance directives,
      and 4) relationships between professionals and their perceived barriers to
      advance directives and hospice and palliative care. METHODS: From several
      consultations with hospice experts, a survey questionnaire was developed to
      solicit responses from professionals on palliative care, dying at home, and
      advance directives. Measures that assessed obstacles to palliative care were
      modified from previous studies to yield composite barrier scores. From a sample
      of a variety of participants at a national conference on palliative care (n =
      200), 101 subjects returned questionnaires (51 percent) yielding 100 usable
      completed forms from attendees who demonstrated an interest in palliative care
      and, in some cases, a high level of personal or professional experience. Survey
      results were analyzed on respondents' perceptions concerning barriers related to
      advance directives and the delivery of palliative care. RESULTS: Of the 13
      obstacle statements, results show that respondents rated the top three barriers
      as 1) physician reluctance to make referrals (mean = 4.23), 2) physician lack of
      familiarity with availability and suitability of hospice (mean = 3.93), and 3)
      association of hospice with death (mean = 3.93). There was a statistically
      significant difference in scores for respondents from hospitals and respondents
      from hospices on their assessment of barriers for the association of hospice with
      death (t = -2.09, p < .05) and the lack of information about the severity of or
      irreversibility of the patients illness (t = -2.78, p < .01).

PMID- 15853090
TI  - A self-care plan for hospice workers.
AB  - Caring for dying patients and their families is a fulfilling, enriching, and
      meaningful experience. It can also be extremely stressful. Maintaining the
      balance between the output and input of energy in a caregiver's professional and
      personal life is an ongoing process. Clinical staff members often formulate plans
      of care for patients. To prevent worker burnout, hospice caregivers must develop
      a plan of self-care to balance their own needs with the needs of their patients.
      The goal of this article is to provide an overview of ways for hospice caregivers
      to relieve stress and develop an individualized self-care plan within the context
      of their work.

PMID- 15853091
TI  - Patient speaking: hospice patients discuss their care.
AB  - Much research examines the effects of hospice assistance on the primary
      caregivers of hospice patients, but very little systematic research has
      investigated the perceptions of hospice patients themselves of the care they
      receive. This researcher asked 38 hospice patients whether and how hospice
      provided comfort, allowing the patients to guide discussion of services. Patients
      reported that hospice helped them by providing human contact, allowing open
      discussion and communication with other health professionals, providing
      assistance with tasks they could no longer do for themselves, and providing
      physical measures to alleviate discomfort.

PMID- 15853092
TI  - The use of metal or plastic needles in continuous subcutaneous infusion in a
      hospice setting.
AB  - OBJECTIVES: Battery-driven portable syringe drivers are a convenient method for
      administering many drugs by continuous subcutaneous infusion (CSCI) to patients
      who cannot swallow medications. At the St. Clare Hospice, nurses usually use
      plastic needles to minimize needlestick injury but sometimes have patients
      transferred to metal needles. This study retrospectively examines this practice
      and its effectiveness. METHODS: The duration of audit was four months. During
      this period, there were 40 patients (23 women, 17 men), who required their
      medications delivered by CSCI. A total number of 74 sites were used. Metal or
      plastic needle CSCIs connected with one-hour release Graseby Syringe Drivers were
      used. The syringes were set to deliver 2 mm/hour. The maximum volume syringe used
      was 50 ml. The data were collected retrospectively. Analysis and results. Sixteen
      patients (21.6 percent) developed minor complications (13 plastic, three metal).
      Among them, 16 showed inflammation. Two patients (3.5 percent) showed slight
      bleeding. Only one patient (1.7 percent) showed local infection (metal). In 14
      patients (18.9 percent), the needle was reinserted due to various reasons,
      including needles pulled out by patients or needles falling out due to unknown
      reasons. There were no needlestick injuries reported, and the staff members
      reported that all problems encountered were easy to identify and resolve.
      CONCLUSION: Plastic needle CSCI prevents needlestick injury and gives minimum
      distress to the patients. More research is needed to determine the local side
      effects of drugs used and the strategies to resolve these problems.

PMID- 15853093
TI  - Central nervous system aspergillosis in an immunocompetent patient: cure in a
      hospice setting with very high-dose itraconazole.
AB  - Aspergillosis of the central nervous system (CNS) is a rare condition with
      exceedingly high mortality. This study describes the case of an immunocompetent
      42-year-old man with a history of intravenous drug use and hepatitis C who
      developed multiple Aspergillus lesions in the cerebellum. Despite neurosurgery
      and antifungal therapy with amphotericin B, he had a protracted hospital course
      with multiple complications, eventually developing cognitive and motor impairment
      due to progressive cerebellar lesions. After transfer to hospice and palliative
      care service, oral itraconazole was escalated to 1600 mg/day with the hope of
      palliating headache, nausea, and cognitive impairment. Remarkably, the patient
      stabilized and improved over time. After 14 months, this unprecedented high-dose
      regimen was discontinued, and the patient was discharged home with only mild
      cerebellar motor impairment.

PMID- 15853094
TI  - Deep vein thrombosis (DVT) in advanced cancer patients with lower extremity edema
      referred for assessment.
AB  - Lower extremity edema is a common complication in advanced cancer patients, and
      deep vein thrombosis (DVT) is one among many causes. Clinical signs and symptoms
      are known to be unreliable, and radiographic investigations are often required in
      diagnosing DVT. A retrospective chart review was conducted on 46 advanced cancer
      patients with lower extremity edema. Researchers analyzed 52 venous duplex scans
      to determine the radiographic incidence of DVT the reliability of other clinical
      signs and symptoms in diagnosing DVT, apart from leg edema, and to assess other
      potential causes of lower extremity edema and their correlation to DVT. Twenty
      three (44 percent) of 52 scans were positive for DVT. The most common
      presentation of edema in the patients with positive scans was bilateral
      asymmetric edema (11/23, 48 percent). There was limited documentation of other
      clinical signs and symptoms suggesting DVT. Other variables such as serum albumin
      (p = 0.46) and creatinine (p = 0.11) were not statistically different in patients
      who had positive and negative scans. Of other potential causes of lower extremity
      edema, such as previous surgery, radiotherapy, tumor, or lymph node compression,
      a number of patients had a coexisting DVT with bilateral asymmetric edema as the
      most common presentation. The results of this study suggest that advanced cancer
      patients with bilateral asymmetric lower extremity edema of potentially
      multifactorial origin have a high incidence of DVT.

PMID- 15853095
TI  - Too beautiful: insights for the end-of-life process.

PMID- 15853096
TI  - Case study: Sedation for palliation of terminal symptoms (SPTS), and nutrition
      and hydration at end of life.

PMID- 15853097
TI  - Polishing occlusal surfaces of direct Class II composite restorations in vivo.
AB  - This study evaluated the effects of four polishing methods on the occlusal
      surfaces of direct Class II composite restorations under clinical conditions.
      Forty premolars and 40 molars were treated with direct Class II restorations
      using the hybrid composite Herculite XRV (Kerr). After placement of the
      restorations, all of which were on occlusal surfaces, they were finished with a
      sequence of 30 microm diamonds and tungsten carbide instruments. Twenty
      restorations each, consisting of 10 premolars and 10 molars, were polished with
      one of the four following methods: (1) Diafix-oral (Mueller-Dental), (2) MPS gel
      (Premier), (3) P 403-W (Dentsply) and (4) Occlubrush (KerrHawe). Selection of the
      polishing methods followed a randomized protocol. Replicas of the restored teeth
      were fabricated and the occlusal surfaces were evaluated quantitatively for
      roughness with the help of profilometry. Qualitative assessment of the surfaces
      by SEM was done with respect to roundness of contours and surface roughness. The
      results were analyzed statistically by two-way ANOVA, chi-squared test for
      crosstables and Kruskal-Wallis test. Analysis of the quantitative data showed
      that there was no significant effect of the polishing methods on occlusal surface
      roughness (p>0.05). Localization of the restoration in premolars or molars had no
      effect on surface roughness (p>0.05). With respect to occlusal relief, SEM
      examination revealed that the use of the Occlubrush resulted in significantly
      more edged contours compared to the other polishing methods (p=0.008).
      Qualitative roughness evaluation showed that there were no significant
      differences among the four polishing methods (p>0.05).

PMID- 15853098
TI  - Response of human pulp capped with a bonding agent after bleeding control with
      hemostatic agents.
AB  - PURPOSE: This study evaluated the response of human pulps capped with a bonding
      agent after bleeding control with different hemostatic agents. MATERIAL AND
      METHODS: Twenty-five Class II cavities were prepared in 25 caries-free human
      premolars scheduled for extraction due to orthodontic treatment. The pulp
      exposures were performed on the occlusal floor. The teeth were randomly divided
      into five groups. Groups 1-4 were capped with an adhesive system after hemostasis
      with different agents: Group 1--saline solution; 2--ferric sulfate; 3--2.5%
      NaOCl; 4--Ca(OH)2 solution. In Group 5, after hemostasis with saline solution,
      the pulp was capped with calcium hydroxide (control group). Then, ScotchBond
      Multi Purpose Plus was applied and the resin composite Z-100 placed incrementally
      according to the manufacturers' directions. After 60 days, the teeth were
      extracted and processed for light microscopic examination (HE) and the groups
      were categorized in a histological score system. The data were subjected to a non
      parametric test (alpha=0.05). RESULTS: Overall, the histological features showed
      that the pulp response from Groups 1 through 4 was inferior to the response from
      Group 5, where dentin bridging occurred. In all groups, where the adhesive system
      was used for capping, the pulp response varied from an acute inflammatory, with
      varying degrees, to necrosis. No dentin bridge was formed after adhesive capping.

PMID- 15853099
TI  - Efficacy, side-effects and patients' acceptance of different bleaching techniques
      (OTC, in-office, at-home).
AB  - This clinical study compared the efficacy of three different bleaching techniques
      with respect to the bleaching times required in order to achieve six grades of
      whitening in human teeth. Any side effects that were noted and the patients'
      acceptance of the method were recorded by a visual analog scale ranging from 0 to
      10. Moreover, epoxy casts from the study teeth were analyzed by scanning electron
      microscopy in order to detect any potential changes in the enamel surface due to
      treatments. Thirty-nine volunteers participated in the study and were allocated
      randomly to one of three different bleaching treatments: Group A (n=13) used
      Whitestrips (over-the-counter technique; one cycle=30 minutes), Group B (n=13)
      used Opalescence PF 10% (at-home bleaching technique; one cycle=8 hours) and
      Group C (n=13) used Opalescence Xtra Boost (in-office bleaching technique; one
      cycle=15 minutes) until a defined whitening of six tabs compared to the baseline
      were reached (assessed by the VITA shade guide). All three methods achieved six
      grades of whitening. The mean treatment time required to reach the defined level
      of whitening was 31.85 +/- 6.63 cycles in Group A, 7.15 +/- 1.86 cycles in Group
      B and 3.15 +/- 0.55 cycles in Group C. All products differed significantly from
      each other in terms of treatment cycles and required treatment time (p<0.001 by
      ANOVA and Mann-Whitney-U-test). Using the VA scale, side effects noted within the
      three groups were minimal. Tooth hypersensitivity ranged from 2.62 (Whitestrips)
      to 3.38 (Opalescence PF), and gingival irritation ranged between 0.23
      (Opalescence Xtra Boost) and 0.85 (Whitestrips). The most accepted method was the
      at-home bleaching technique. None of the teeth studied showed detectable enamel
      surface changes in the subsequent SEM analysis using 200x and 2000x
      magnification.

PMID- 15853100
TI  - Microleakage of compomer restorations in primary teeth after preparation with bur
      or air abrasion.
AB  - This study compared the degree of marginal leakage of a compomer in Class V
      cavities of human primary molars prepared by a conventional dental bur and air
      abrasion with or without acid etching. Fifty-six non-carious extracted primary
      molars were randomly divided into four groups (n=14) to be prepared by four
      techniques: Group-1: Bur followed by acid etching: Class V cavity preparations
      were placed on the buccal surfaces of each tooth using a high-speed handpiece.
      The preparations were 1.5-mm deep, 3-mm long and 2-mm wide, with the occlusal
      margin in enamel and the cervical margin extending 0.5 mm below the cementoenamel
      junction. The preparations were acid etched with 37% phosphoric acid starting at
      the enamel margins for 30 seconds and rinsed with water for 20 seconds. The
      preparations were then restored with Compoglass F. 2-Group 2: Bur: The
      preparations and the treatment procedures were the same as in Group 1, with the
      exception of 37% phosphoric acid application. Group 3: Air abrasion followed by
      acid etching: Class V cavity preparations were placed on the buccal surfaces of
      each tooth using a handpiece of an air-abrasive system (PrepStart, Danville
      Engineering). The system was supplied with dry compressed air at 80 psi. In all
      tests, the air-abrasion system was operated with an 80 degrees-angle handpiece
      tip and 50-mm aluminum oxide particles. A tip with a 0.38-mm inner diameter was
      used at a 2-mm distance. The treatment procedures were the same as in Groups 1
      and 2. Group 4: Air abrasion: The preparations and treatment procedures were the
      same as in Group 3, with the exception of 37% phosphoric acid. After finishing
      the restorations, the teeth were stored in distilled water at 37 degrees C for 24
      hours. The samples were thermocycled for 500 cycles between 5 degrees C and 55
      degrees C with a dwell time of 30 seconds. The samples were then immersed in 0.5
      percent basic fuchsin dye for 24 hours at 37 degrees C. The surface-adhered dye
      was then rinsed in tap water and the teeth were embedded in a chemically
      activated acrylic resin and bisected longitudinally in a mesiodistal direction
      with a low speed diamond disk. Each section was examined under a stereomicroscope
      (Nikon, Tokyo, Japan) at 20x magnification. The data were analyzed statistically
      by Kruskal-Wallis analysis of variance to determine any statistical significant
      differences in microleakage scores among the groups at a p-value of 0.05. Also,
      the enamel versus cementum-dentin microleakage scores of each group were compared
      using z-test at the 0.05 significance level. There was no statistically
      significant difference among the groups (p>0.05), but a statistical difference
      between enamel and cementum-dentin surfaces was evaluated (p<0.05).

PMID- 15853101
TI  - Bond strength and SEM observation of CO2 laser irradiated dentin, bonded with
      simplified-step adhesives.
AB  - This study investigated, mechanically and morphologically, whether the dentin
      surface irradiated by CO2 laser could be a possible adherent when bonded with
      simplified-step adhesives. Buccal enamel and cementum of extracted human
      premolars were removed to expose a flat dentin surface. The dentin surfaces were
      irradiated continuously with CO2 laser at 1.0 W. Before bonding with either a
      single-bottle adhesive (Single Bond) or a self-etching priming system (Mega
      Bond), the irradiated dentin surface was treated as follows: no treatment, NaHCO3
      powder abrasion and wet-grinding with 600-grit SiC paper. The treated dentin
      surfaces were bonded to resin composite with either of the two adhesives. Non
      irradiated dentin surfaces were also used as control. Resin bonded specimens were
      stored in water at 37 degrees C for 24 hours and subjected to microtensile bond
      test. Additionally, to observe the resin/irradiated dentin interface, resin
      bonded specimens were similarly prepared, sectioned into slabs, embedded in epoxy
      resin, polished with diamond pastes, sputter coated Au-Pd and examined with
      scanning electron microscopy (SEM). After SEM observation, the specimens were
      further polished with diamond paste to remove the Au-Pd sputter-coat, immersed in
      HCL and NaOCl and finally observed by SEM again. In the presence of carbonized
      dentin, microtensile bond strength drastically decreased but recovered to the
      control value by removing the carbonized dentin layer visually with SiC paper for
      both adhesive systems. However, the laser-affected dentin that remained on the
      bonded interface was easily dissolved with NaOCl and HCl.

PMID- 15853102
TI  - Effect of prophylaxis regimens on surface roughness of glass ionomer cements.
AB  - This study investigated the surface roughness of conventional (Fuji II Capsulated
      [FC], GC Corporation, Tokyo, Japan), resin-modified (Fuji II LC [FL], GC
      Corporation) [FL] and highly viscous (Fuji IX GP Fast [FN], GC Corporation) glass
      ionomer cements [GICs] after exposure to five prophylaxis regimes. The surface
      roughness obtained was compared to untreated polished specimens (control). The
      prophylaxis regimes evaluated were rotating brush with pumice-water slurry [PB];
      rotating rubber cup with pumice-water slurry [PC]; rotating rubber cup with
      prophylaxis paste [PP]; rotating rubber cup with prophylaxis gel [PG] and air
      powder polishing [PJ]. Forty-eight specimens (3-mm long x 3-mm wide x 2-mm deep)
      were made for each material. The specimens were stored in distilled water at 37
      degrees C for one month, polished with 1200 grit sandpaper using a lapping device
      and randomly divided into six groups (n=8). They were then stored for an
      additional two months in distilled water at 37 degrees C prior to exposure to the
      various prophylaxis regimens. The mean surface roughness value (Ra; microm) was
      measured with a profilometer. Data was subjected to ANOVA/Scheffe's tests at
      significance level 0.05. Mean Ra ranged from 0.30 to 1.70 microm for FC, 0.40 to
      2.52 microm for FL and 0.36 to 1.79 microm for FN. Regardless of the type of
      glass ionomer, treatment with PJ resulted in significantly rougher surfaces when
      compared to the control group. For FC and FN, a significant increase in roughness
      was observed after treatment with PB and PP, respectively. Glass ionomer
      restorations may require re-polishing after exposure to some prophylaxis
      regimens.

PMID- 15853103
TI  - Curing depth of a resin-modified glass ionomer and two resin-based luting agents.
AB  - The degree of conversion of resin-based luting agents used for retention of
      prefabricated posts has been questioned due to the difficulty of light
      penetration into the resin-filled root canal. This study evaluated the depth of
      cure of a resin-modified glass ionomer cement (Rely X--3M ESPE) and two resin
      based luting agents (Rely X ARC--3M ESPE and Enforce-Dentsply). Twenty-four
      14x2x2mm3 specimens were prepared in a Teflon split mold with the three luting
      agents (n=8). After preparation, the specimens were stored at 37 degrees C in a
      dark box for 24 hours prior to microhardness testing. Measurements of Knoop
      hardness were performed at three different depths: superficial, medium and deep
      thirds. The results (KHN) were statistically analyzed by repeated measures ANOVA
      and Tukey test (0.05), which showed that resin-based luting agents presented the
      highest Knoop hardness values within the superficial third. Within the medium
      third, there were no significant differences among luting materials. However,
      within the deep third, Rely X presented the highest values. KHN values of resin
      based luting agents decreased remarkably as depth increased.

PMID- 15853104
TI  - The assessment of unaided visual examination, intraoral camera and operating
      microscope for the detection of occlusal caries lesions.
AB  - This study compared the efficiency of unaided visual examination, intraoral
      camera and operating microscope according to a visual scoring system (ERK) at
      occlusal caries detection. A total of 84 extracted human molars were mounted to
      create mouth models with a premolar in contact on both sides. The models were
      examined in a phantom head simulating clinical conditions by four observers using
      the three techniques: unaided visual examination, an intraoral camera and on
      operating microscope according to the ERK scale. The teeth were than sectioned in
      a mesio-distal direction and examined under a stereomicroscope with 10x
      magnification for histological validation. The sensitivity, specificity, positive
      predictive and negative predictive values were calculated for the four observers
      with three techniques and statistical analyses were performed using Friedman and
      DUNN tests, while strength of agreement was determined by calculating Kappa
      values. From the data, mean sensitivity values were cal. culated as 0.26, 0.43,
      0.49 and mean specificity values as 0.87, 0.80 and 0.73 for unaided visual
      examination, intraoral camera and operating micro scope, respectively. The Kappa
      values ranged between 0.187 and 0.301 for visual examination, 0.328 and 0.459 for
      intraoral camera and 0.363 and 0.516 for operating microscope. As a result, the
      use of an intraoral camera and operating microscope improved occlusal caries
      detection according to the ERK scale.

PMID- 15853105
TI  - Microtensile bond strengths of one-step and self-etching adhesive systems.
AB  - The microtensile bond strength of resin composite bonded to human enamel was
      evaluated utilizing four light-cure bonding agents. Human third molars were
      embedded in auto-cure acrylic and the buccal surfaces were sequentially abraded
      to 400 grit. Resin composite cylinders were then bonded using the four bonding
      systems according to the manufacturer's specifications. Each bonded tooth
      produced three to four longitudinal sections which were then laterally notched to
      give a square bond area (approximately 2.25 mm2). Specimens (n=10) were assigned
      to two groups: Group I was stored in distilled water at 37 degrees +/- 2 degrees
      C for seven days. Group II was stored in distilled water at 37 degrees +/- 2
      degrees C for seven days, during which time it was thermocycled in hot and cold
      water baths for 1,000 cycles. In addition, a water sorption test was performed on
      three of the four adhesive systems. The microtensile bond strength of the
      conventional adhesive Optibond Solo Plus was significantly greater than that of
      the self-etching adhesives Tyrian SPE and Prompt L-Pop. Adhesive systems that
      were more hydrophilic tended to show lower bond strengths, especially after
      thermocycling.

PMID- 15853106
TI  - The in vitro morphological effects of some current pre-treatments on dentin
      surface: a SEM evaluation.
AB  - This in vitro study morphologically evaluated the effect of some current surface
      pre-treatments on dentin, using scanning electron microscopy, and related these
      morphological alterations to clinical implications. The labial surfaces of 30
      bovine lower incisors were ground to obtain a flat dentin surface and were
      finished with 600-grit SiC paper to produce standardized smear layers. The teeth
      were randomly divided into six groups of five each. Group 1 was the control
      group, smear layer covered dentin; Group 2 was etched with 37% phosphoric acid
      (PA) for 15 seconds; Group 3, 37% PA for 15 seconds, followed by 10% NaOCl for 60
      seconds; Group 4, 10% NaOCl for 60 seconds; Group 5, a self-etching primer
      (Clearfil SE Bond, CSEB-primer) was applied for 20 seconds; Group 6, CSEB-primer
      for 20 seconds, followed by NaOCl for 60 seconds. The specimens were fixed,
      dehydrated, dried and analyzed by SEM. Treatment with 37% PA removed the smear
      layer, funneled the tubules and resulted in a collagen-rich surface which
      appeared to have collapsed in its outermost part, producing a dense surface layer
      covered with silica particles. When 37% PA treatment was followed by 10% NaOCl,
      the collagen network was removed to reveal an eroded, rough mineral surface with
      numerous lateral branches and larger than normal tubular orifices. The action of
      10% NaOCl on the smear layer-covered dentin showed no significant alteration in
      surface morphology. The treatment with CSEB-primer dissolved the smear layer but
      only partially dissolved the smear plugs. The tubules did not present the typical
      funnel shape seen following PA treatment. These morphological aspects on dentin
      surface must influence bonding results. The dentin surface alterations produced
      by PA appeared to be a very severe demineralization pattern, quite irregular and
      less permeable to monomer infiltration, while the surface provided by the self
      etching primer appeared to be a more uniform, less porous surface, and the
      association with simultaneous monomer infiltration may reduce the occurrence of
      mistakes in clinical bonding procedures.

PMID- 15853107
TI  - Influence of different beverages on the microhardness and surface roughness of
      resin composites.
AB  - This study assessed the influence of different beverages on the microhardness and
      surface roughness of microfilled (A110, 3M/ESPE), hybrid (Z250 3M/ESPE) and
      flowable (Flow, 3M/ESPE) resin composites, over time. Twenty-four disc-shaped
      specimens (10 mm; 2-mm thick) of each resin composite were fabricated, thereby
      forming three groups (n=24). Knoop microhardness and surface roughness (Ra) were
      analyzed at predetermined evaluation periods: 24 hours, and 7, 30 and 60 days
      after specimens fabrication. The 24-hour measurements were recorded after storage
      in artificial saliva. Next, each group (n=24) was divided into four subgroups
      (n=6) according to the test beverages: Coca-Cola, sugar cane spirit, coffee and
      artificial saliva (control). Control specimens were kept in saliva throughout the
      experiment (60 days). For experimental specimens, a 60-day testing cycle was
      carried out: specimens were initially stored in saliva for four hours, then
      submitted to a five-minute immersion in the beverages (Coca-Cola, sugar cane
      spirit, coffee) intercalated by immersions in saliva three times daily.
      Microhardness/roughness measurements were done at 7-, 30- and 60-day intervals.
      Data were submitted to three-way ANOVA and Scheffee test (p<0.05). It was
      observed that the tested beverages somewhat altered (p<0.05) the composites'
      microhardness and/or surface roughness. Knoop microhardness-for all resin
      composites, microhardness remained stable up to the 30-day record, decreasing
      significantly at the 60-day evaluation. During the interaction beverage X
      evaluation period, it was observed that the microhardness of materials immersed
      in coffee and Coca-Cola remained stable up to the seven-day measurement, showing
      a decrease at the 30-day record and a more accentuated drop at the 60-day
      evaluation (p<0.05). Specimens immersed in sugar cane spirit exhibited no
      significant change in microhardness up to the seven-day measurement, increasing
      significantly at the 30-day record and later decreasing at the 60-day evaluation.
      Surface Roughness--For all resin composites, surface roughness increased at the
      seven-day measurement, while decreasing at the 30-day record and even more at the
      60-day record. In the interaction beverage X evaluation period, the surface
      roughness of specimens immersed in test beverages increased at the seven-day
      measurement, showing a gradual decrease at the following records (30- and 60-day
      evaluations). The findings of the reported research disclosed that all beverages
      altered, to some degree, the microhardness and/or surface roughness of the tested
      resin composites. The alterations' effects ranged from slightly adverse to a
      markedly negative impact on the composites' microhardness and surface roughness,
      depending on the characteristics of the materials, type of beverage and the
      evaluated period. Generally, the greater number of immersions in beverages
      resulted in a more accentuated impact on the resins' properties.

PMID- 15853108
TI  - The influence of fatigue loading on the quality of the cement layer and retention
      strength of carbon fiber post-resin composite core restorations.
AB  - Clinical studies have shown that endodontically treated teeth restored with short
      posts or deficient ferrules show a high failure risk. This study. evaluated the
      influence of fatigue loading on the quality of the cement layer between
      prefabricated quartz coated carbon fiber posts with restricted length and the
      root canal wall in maxillary pre-molars. Two adhesive resin composite cements,
      chemical-cured Panavia 21 (Group 1) and dual-cured RelyX-ARC (Group 2), and one
      resin-modified glass-ionomer cement, chemical-cured RelyX (Group 3), delta were
      selected for this study. Post- and-core restorations were made on single-rooted
      human maxillary premolars from which the coronal sections were removed at the
      level of the proximal cemento-enamel junction (CEJ). Following endodontic
      treatment, a post-and-core restoration with 6-mm post length was prepared for
      each tooth. The posts were directly cemented into the root canal and, after
      applying an adhesive (Clearfil Photo Bond), they were built up with a core build
      up composite (Clearfil Photo Core). For each group (n=8), half of the specimens
      were exposed to fatigue loading (10(6) load cycles) almost perpendicular to the
      axial axis (85 degrees), while the other half were used as the control. Three
      parallel, transverse root sections, 1.5-mm thick, were cut from each specimen at
      the apical, medial and coronal location. These sections were examined by Scanning
      Electron Microscopy (SEM) to evaluate the integrity of the cement layer, while
      the retention strength of the cemented post sections was determined with the push
      out test. The multivariate results of MANOVA showed that the condition main
      effect (fatigue or control) was not significant (p=0.059); the two other main
      effects, type of cement and section location, were significant (p=0.001 and
      p=0.008). For both the push-out strength and SEM evaluation of the cement layer
      integrity, the results significantly improved from RelyX to RelyX-ARC to Panavia
      21 and also from apical to coronal.

PMID- 15853109
TI  - Bonded amalgam restorations: microleakage and tensile bond strength evaluation.
AB  - PURPOSE: The objective of this study was to evaluate the tensile bond strength
      (BS) and microleakage (MI) of bonded amalgam restorations to dentin when an
      unfilled and a filled system are used under three application modes. MATERIAL AND
      METHODS: Seventy-two and 96 human molars, respectively, were employed for BS and
      MI tests. For BS, the occlusal surface of the molars was ground flat until dentin
      exposure. A 3-mm area was delimited for bonding. For MI, Class V cavities were
      prepared in the CEJ (4 mm x 4 mm x 2 mm). For each test, the molars were randomly
      divided into six treatment groups defined by a combination of the levels:
      Adhesive system (Scotchbond Multi-Purpose Plus [SBMP], Optibond dual cure [OPTB])
      and Application mode (light-LC, chemical-C and combination of light and chemical
      curing-LCC). After adhesive application, the amalgam was condensed into a Teflon
      mold (BS) and into the cavities (MI). After storage in saline solution for seven
      days at 37 degrees C, the specimens were subjected to the BS test at 0.5
      mm/minute. For microleakage evaluation, the restorations were sealed with nail
      varnish, except for an area 1 mm around the restoration, immersed in 5% methylene
      blue solution for 24 hours and sectioned into two halves. Each half was evaluated
      by two trained examiners at 25x magnification in a 0-3 score system and the
      highest score was recorded. The BS data was evaluated by two-way ANOVA and
      Tukey's test (alpha=0.05). The MI data were analyzed by Kruskal Wallis and Mann
      Whitney tests (alpha=0.05). RESULTS: The main factors were significant for the BS
      test: the highest BS mean was obtained using the LCC technique and the OPTB
      system. Regarding the MI test, only the application mode was significant: lower
      dye infiltration was observed for LC and LCC.

PMID- 15853110
TI  - Effect of flexural load cycling on microleakage of extended root caries
      restorations.
AB  - This study evaluated the microleakage of resin-modified glass ionomer, flowable
      compomer and flowable resin composite restorations on a Class V cavity of
      simulated advanced root caries under a flexural load cycling condition. Thirty
      six non-carious human maxillary premolars were mounted in cylindrical acrylic
      resin molds. The cavities were prepared in the proximal root surface, from the
      middle of the buccal surface to the middle of the lingual surface, approximately
      1 mm below the cemento-enamel junction, 2 mm axial width and 1.2 mm in depth. The
      teeth were randomly assigned to one of three groups with 12 teeth in each group:
      Group 1: Cavity conditioner and Fuji II LC (GC America), Group 2: Prime & Bond NT
      and Dyract Flow (Caulk-Dentsply), Group 3: Excite and Tetric flow
      (Ivoclar/Vivadent). Specimens were settled laterally on a fatigue-testing machine
      that was adjusted to deliver a force of 60N. The specimens were load cycled at 1
      Hz for 5000 cycles, placed in a staining solution and sectioned to evaluate
      microleakage penetration. Results indicate that the coronal and gingival margins
      showed significant microleakage differences among the three restorations
      (p<0.05). At the coronal margin, there was no significant difference between
      Groups 2 and 3. At the gingival margin, there was no significant difference
      between Groups 1 and 2. It was concluded that the marginal sealing ability of a
      flowable resin composite under a flexural cycling load was better than in other
      selected materials and that flowable resin composite with dentin adhesive was a
      desirable alternative for root caries restorations extended to the proximal
      surface.

PMID- 15853111
TI  - Flexural properties of eight flowable light-cured restorative materials, in
      immediate vs 24-hour water storage.
AB  - This study evaluated the flexural strength, flexural modulus, modulus of
      resilience and water sorption of eight flowable light-cured restorative materials
      compared with two conventional restoratives (as control). Forty specimens of each
      material were made. Twenty specimens were immediately flexural tested, while the
      remaining 20 were weight-measured and immersed in distilled water in a 37 degrees
      C incubator. After 24 hours, the samples were weight-measured again to identify
      water sorption and they were flexural tested. The findings were statistically
      analyzed using t-test, one-way ANOVA, Tukey test and Pearson's Product-Moment
      Correlation. The results of the flexural strength test were also analyzed using
      Weibull statistic. All flowable light-cured restorative materials except Palfique
      Estelite Low Flow exhibited immediate flexural strength values between the
      conventional ones. All flowable light-cured restorative materials showed 24-hour
      flexural strength values between the conventional ones. The Weibull modulus for
      immediate flexural strength of the materials varied from 6.37 to 15.23, while for
      24-hour flexural strength, the strength varied from 8.10 to 14.30. In both
      conditions, all flowable light-cured resin composites showed lower flexural
      moduli but higher modulus of resilience than the conventional ones. The water
      sorption of all resin composites was lower than the flowable light-cured
      compomer. There was a distinct relation (r=-0.84, p<0.01) between the increasing
      ratio in modulus of resilience and the amount of water sorption.

PMID- 15853112
TI  - Influence of disinfectants on dentin bond strength of different adhesive systems.
AB  - The influence of water disinfectants used in dental unit waterlines on the dentin
      bonding of different adhesive systems was investigated by using push-out tests.
      Three hundred and twenty dentin disc specimens were prepared from caries-free
      human molars. In each specimen, a standardized conical cavity was prepared while
      cooling with water from a dental unit containing one of three different
      disinfectants (n=80 each group; A=control: water without disinfectant, B: Alpron
      neutral, C: Alpron mint, D: Dentosept P). Subsequent rinsing of the cavities was
      performed With the respective disinfectant. The cavities were filled with the
      following combinations of dentin adhesives and composites, resulting in 16
      subgroups (n=20): Syntac Classic/Tetric Ceram, Clearfil Liner Bond 2V/Luxacore,
      OptiBond FL/Prodigy and Prime&Bond NT/Spectrum. After polishing the fillings, one
      half of each subgroup (n=10) was stored in water (37 degrees C) for 24 hours. The
      other half was stored in water (37 degrees C) for 180 days and additionally
      thermocycled (2000 cycles at 5/55 degrees C). The bond strength was then measured
      by push-out tests. Statistical analysis of the data was carried out using ANOVA
      and pairwise t-tests (Significance level p < or = 0.01). The disinfectants showed
      no significant influence on the loads required for debonding of Syntac
      Classic/Tetric Ceram, Clearfil Liner Bond 2V/Luxacore and OptiBond FL/Prodigy as
      compared to the controls. However, the use of disinfectants in the water supply
      of a dental unit decreased dentin bond strength in the specimens filled with
      Prime&Bond NT/Spectrum. Disinfectants in the water of dental unit waterlines may
      have an influence on dentin bonding, depending on the adhesive system used.

PMID- 15853113
TI  - Thermal emission and curing efficiency of LED and halogen curing lights.
AB  - The purpose of this study was to compare the thermal emission and curing
      efficiency of LED (LEDemetron 1, SDS/Kerr) and QTH (VIP, BISCO) curing lights at
      maximum output and similar power, power density and energy density using the same
      light guide. Also, another LED curing light (Allegro, Den-Mat) and the QTH light
      at reduced power density were tested for comparison. Increase in temperature from
      the tips of the light guides was measured at 0 and 5 mm in air (23 degrees C)
      using a temperature probe (Fluke Corp). Pulpal temperature increase was measured
      using a digital thermometer (Omega Co) and a K-type thermocouple placed on the
      central pulpal roof of human molars with a Class I occlusal preparation.
      Measurements were made over 90 seconds with an initial light activation of 40
      seconds. To test curing efficiency, resin composites (Z100, A110, 3M/ESPE) were
      placed in a 2-mm deep and 8-mm wide plastic mold and cured with the LED and QTH
      curing lights at 1- and 5-mm curing distances. Knoop Hardness Numbers (KHN) were
      determiped on the top and bottom surfaces (Leco). Bottom hardness values were
      expressed as a percentage of maximum top hardness. No significant differences
      were found in maximum thermal emission or KHN ratios between the LED (LEDemetron
      1) and the QTH (VIP) at maximum output and similar energy densities
      (ANOVA/Tukey's; alpha=0.05).

PMID- 15853114
TI  - The effect of whitening agents on caries susceptibility of human enamel.
AB  - This in vitro study evaluated whether the treatment of human enamel with
      whitening agents containing different concentrations of carbamide or hydrogen
      peroxide changes the susceptibility of enamel to caries. Twenty-four sound human
      incisors were selected for this study. For each tooth, the crown was sectioned
      into two halves in the cervical-incisal direction. One half of the sectioned
      tooth was treated and the other half was used as a control specimen. Each half
      was randomly divided into three treatment groups (eight two-halves/group). The
      whitening agents were 10% carbamide peroxide, 20% carbamide peroxide with
      fluoride and 35% hydrogen peroxide. Following pretreatment, the specimens were
      demineralized for four days in an in vitro microbial caries model and then
      analyzed using a confocal laser scanning microscope (CLSM). Results showed that
      there were no significant differences between the treated and controlled
      specimens for teeth treated with 10% carbamide peroxide or 35% hydrogen peroxide.
      However, specimens treated with 20% carbamide peroxide with FP (0.11% fluoride
      and potassium nitrate) were less susceptible to caries than their controls at p <
      or = 0.05. In conclusion, application of bleaching agents does not increase the
      caries susceptibility of human enamel.

PMID- 15853115
TI  - Are doctors fit to manage type 2 diabetes?

PMID- 15853116
TI  - Evidence-based European guidelines on diet and diabetes.

PMID- 15853117
TI  - Prudent diet and the risk of insulin resistance.
AB  - BACKGROUND AND AIM: Diet is a potentially modifiable risk factor for diabetes.
      Dietary patterns may exert greater effects on health than individual foods,
      nutrients or food groups. Data on associations between dietary patterns and the
      risk of insulin resistance and type 2 diabetes are sparse. The aim of the study
      was to examine associations between dietary patterns and the risk of insulin
      resistance. METHODS AND RESULTS: We performed a cross sectional study involving a
      group of 1018 men and women, sampled from 17 general practice lists in the South
      of Ireland, with a response rate of 69%. Participants completed a detailed health
      and lifestyle questionnaire and provided fasting blood samples for analysis of
      glucose, insulin and lipids. Dietary intake was assessed using a food frequency
      questionnaire. The food frequency questionnaire was a modification of the UK arm
      of the European Prospective Investigation into cancer, EPIC study, which was
      based on that used in the US Nurses' Health Study. Dietary patterns were assessed
      by K cluster analysis. Insulin resistance was estimated on the basis of fasting
      glucose and insulin, using the glucose homeostasis model (HOMA scores). Insulin
      resistance was defined as the upper quartile of the HOMA scores. Three dietary
      patterns were identified by cluster analysis (traditional Irish diet, a prudent
      diet and an alcohol and convenience foods diet). Participants in clusters 1
      (traditional Irish diet) and 3 (high alcohol and convenience foods) had a lower
      intake of more 'healthy' food groups (such as fruit, vegetables, low fat dairy
      products, poultry, fish and whole grain products) and higher intake of foods
      richer in total and SFA content (such as high fat dairy products, butter, meat
      and meat products). Cluster 2 (prudent dietary pattern) was characterized by a
      higher intake of food groups that are typically recommended in health promotion
      programs and a lower intake of meat (read meat), meat products, sweets, high fat
      dairy and white bread (white bread and unrefined cereal). The prudent diet had
      the lowest HOMA scores in analysis of covariance. The prevalence of insulin
      resistance in the prudent diet was lower than that in the traditional diet
      (OR=0.53; 95%CI, 0.33-0.85 in fully adjusted analysis). CONCLUSION: A prudent
      diet may be associated with enhanced insulin sensitivity and a lower risk of type
      2 diabetes.

PMID- 15853118
TI  - Can foods with added soya-protein or fish-oil reduce risk factors for coronary
      disease? A factorial randomised controlled trial.
AB  - BACKGROUND AND AIMS: To develop functional foods which are capable of reducing
      key risk factors for coronary heart disease in an at risk population. The
      specific hypothesis tested here was that providing bread, cracker biscuits and
      snack bars fortified with DHA (long-chain omega 3) and soya-protein would havd a
      positive impact on cholesterol and blood pressure. METHODS AND RESULTS: A
      pragmatic, double-blind, factorial placebo-controlled randomised trial recruiting
      213 middle-aged men and women with untreated elevated total cholesterol or blood
      pressure. The factors examined were the effect of giving supplies of bread,
      cereal bars and cracker biscuits fortified with 2 g fish oils (DHA, 22: 6n-3), or
      25 g soya-protein (containing 50 mg of isoflavonoids) for five weeks. Primary and
      secondary outcomes included total, low-density and high-density cholesterol (HDL
      C), and systolic and diastolic blood pressure. Compliance was assessed using
      biomarkers and food intake histories. DHA enriched foods increased HDL-C by 6.0%
      (95% CI 2.5%, 9.6%) but had no effect on total or low-density cholesterol or
      blood pressure. Overall, soya-protein did not influence any of the outcomes
      assessed. However, in women only, soya-protein increased systolic blood pressure
      by 5.9% (95% CI 1.73, 9.9%). CONCLUSIONS: Adding DHA (fish-oils) to staple foods
      might supplement existing methods to help reduce CVD morbidity and mortality.
      However, these findings highlight the importance of ensuring that functional
      foods do not present any harms to particular subgroups within a general
      population, if they are to be made freely available to consumers. This latter
      point requires further attention by the research community in relation to soya
      protein.

PMID- 15853119
TI  - Cardiac lipids and antioxidant status in high fructose rats and the effect of
      alpha-lipoic acid.
AB  - BACKGROUND AND AIMS: The development of insulin resistance has been shown to be
      an early step in the development of cardiovascular diseases in diabetic patients.
      Oxidative stress may be important in the development of coronary artery disease.
      Fructose loaded rats, which show the characteristic features of insulin
      resistance, also display an imbalance between the peroxidation process and the
      antioxidant system. Alpha-lipoic acid (LA)--a co-enzyme--is known for its potent
      antioxidant effects. The present study examined whether LA mitigates fructose
      induced oxidative stress in heart tissue. METHODS AND RESULTS: Male Wistar rats
      with a body weight of 150-170g were divided into 4 groups of 6 rats each. Control
      rats received a control diet containing starch and water ad libitum. Fructose
      rats received a fructose-enriched diet (>60% of total calories). Fructose + LA
      rats received a fructose diet and alpha-lipoic acid (35mg/kg b.w i.p.). Control +
      LA rats received control diet and alpha-lipoic acid. After the 20-day treatment
      period, we assessed the insulin sensitivity index in terms of HOMA. The levels of
      lipid peroxidation markers and the enzymatic and non-enzymatic antioxidant status
      in the heart tissue were measured. Plasma and heart tissue lipids were also
      analysed. Fructose rats showed decreased insulin sensitivity as reflected by high
      values of HOMA, increased peroxidation, impaired antioxidant status and lipid
      abnormalities in the cardiac tissue. These abnormalities were attenuated and the
      antioxidant levels were enhanced by LA. The reduction in HOMA values suggests LA
      improves insulin sensitivity. CONCLUSIONS: Improvement of insulin sensitivity and
      enhancement of cardiac antioxidant status suggest that LA may be useful as a
      cardioprotective agent in insulin-resistant states.

PMID- 15853120
TI  - Effect of non-enzymatic glycation on aluminium-induced lipid peroxidation of
      human high density lipoproteins (HDL).
AB  - BACKGROUND AND AIM: Several studies have shown that non-enzymatic glycation and
      oxidative damage play an important role in the pathogenesis of neurological
      diseases. Increased levels of advanced glycation end-products (AGEs) and of lipid
      peroxidation products have been observed in the brain, in the cerebrospinal fluid
      (CSF) and in the plasma of subjects affected by Alzheimer's disease (AD). The aim
      of this study was to investigate the effect of non-enzymatic glycation on
      aluminium-induced lipid peroxidation and on the stimulatory effect exerted by
      aluminium on iron-triggered oxidation of high density lipoproteins (HDL) isolated
      from human plasma. METHODS AND RESULTS: Aluminium (10-200 microM) and iron (20
      microM) induced a significant increase in lipid hydroperoxides in HDL compared to
      untreated HDL. Therefore, our results confirm that aluminum and iron exert an
      oxidant effect on HDL. Moreover, aluminium exerted a stimulatory effect on iron
      induced lipid peroxidation of HDL, in agreement with our previous studies. The
      aluminum/iron-induced increase in lipid hydroperoxides was significantly higher
      in HDL incubated for different time periods (24-72 hours) in the presence of 50
      mM glucose (Gly-HDL) compared to HDL incubated alone. These results demonstrate
      that Gly-HDL is more susceptible to aluminium and iron-oxidative treatment with
      respect to control HDL. CONCLUSION: We suggest that aluminium and iron-induced
      oxidative damage on HDL could be involved in the development of neurological
      diseases and that glycation of HDL could represent an additional risk factor for
      these human diseases.

PMID- 15853121
TI  - Insulin sensitivity assessment in uncomplicated obese women: comparison of
      indices from fasting and oral glucose load with euglycemic hyperinsulinemic
      clamp.
AB  - BACKGROUND AND AIM: Obesity is associated with a great variability to insulin
      sensitivity degree. Several formulae developed from measurements in the fasting
      state and during the oral glucose tolerance test (OGTT) have been proposed to
      assess insulin sensitivity. AIM: In this work we sought to compare the published
      insulin sensitivity indices with the metabolized glucose index obtained by
      hyperinsulinemic euglycemic clamp in uncomplicated obese subjects. Uncomplicated
      obesity provides a good model in order to study insulin sensitivity per se.
      METHODS AND RESULTS: In this protocol, 65 obese women affected by uncomplicated
      obesity (without impaired glucose tolerance, diabetes, hypertension and
      dyslipidemia) underwent 2 h OGTT and euglycemic hyperinsulinemic clamp. Common
      formulae obtained in the fasting state and from a 2h OGTT were calculated. Simple
      linear regression analysis showed that ISI (r=0.592, p=0.01), 2 h OGIS (r=0.576,
      p=0.02), MCRest (r=0.507, p=0.02), 120 insulin (r=-0.494, p=0.03) and fasting
      insulin (r=-0.382, p =0.02) are significantly correlated to the M index obtained
      from the hyperinsulinemic euglycemic clamp. The Bland-Altman plot confirmed the
      good agreement between indices from OGTT and the clamp. CONCLUSION: OGTT-derived
      indices provide a good assessment of insulin sensitivity in obesity. OGTT could
      easily be applied in a large number of obese patients in order to obtain
      information on both glucose tolerance and insulin sensitivity.

PMID- 15853122
TI  - Evidence-based nutritional approaches to the treatment and prevention of diabetes
      mellitus.

PMID- 15853123
TI  - A controlled study of the use of autologous platelet gel for the treatment of
      diabetic foot ulcers.

PMID- 15853124
TI  - Mediterranean diet score: correlation with 25-year mortality from coronary heart
      disease in the Seven Countries Study.

PMID- 15853125
TI  - A healer or an executioner? The proper role of a psychiatrist in a criminal
      justice system.

PMID- 15853126
TI  - A death by any other name: the federal government's inconsistent treatment of
      drugs used in lethal injections and physician-assisted suicide.

PMID- 15853127
TI  - Bioterrorism defense: are state mandated compulsory vaccination programs an
      infringement upon a citizen's constitutional rights?

PMID- 15853128
TI  - A tripartite threat to medical records privacy: technology, HIPAA's privacy rule
      and the USA Patriot Act.

PMID- 15853129
TI  - Ohio's patient-physician privilege: whether planned parenthood is a protected
      party.

PMID- 15853130
TI  - Prohibiting procreation: a step in the right direction to protect the children of
      deadbeat dads; an analysis of the court decision in State v. Oakley.

PMID- 15853131
TI  - Do Not Resuscitate decision-making: Ohio's Do Not Resuscitate law should be
      amended to include a mature minor's right to initiate a DNR order.

PMID- 15853132
TI  - What successful companies know that law firms need to know: the importance of
      employee motivation and job satisfaction to increased productivity and stronger
      client relationships.

PMID- 15853133
TI  - Template guided self-assembling two-dimensional array of Au@SiO2 core-shell
      nanoparticles for room-temperature single electron transistors.
AB  - The composite nanoparticles of a gold core capped by a SiO2 shell with well
      controlled thickness have been synthesized and fabricated into two-dimensional
      array on silicon surface by a simple self-assembly method combined with an AFM
      nanolithography technique. Current-voltage measurements of the Au@SiO2 composite
      nanoparticles (shell thickness of 6 nm) show a well-pronounced Coulomb staircase
      with a period of 300 mV at room temperature, demonstrating single electron
      transistor behavior. The step width of the Coulomb staircase can be tuned by
      controlling the thickness of SiO2 shell. The tunable single electron tunneling
      properties make the 2D array of Au@SiO2 composite nanoparticles an ideal
      candidate for planar single electron transistor devices.

PMID- 15853134
TI  - Synthesis and characterization of Dy(OH)3 and Dy2O3 nanotubes.
AB  - Dy(OH)3 nanotubes with high aspect ratios of up to about 50 were synthesized in
      the presence of poly(ethylene glycol) via a hydrothermal method. Poly(ethylene
      glycol), as a nonionic surfactant, plays an important role in the formation of
      morphologies. Subsequent thermal treatment of Dy(OH)3 nanotube precursors at 450
      degrees C for 6 h led to Dy2O3 nanotubes, during which the precursor tubular
      morphology was maintained. Selected-area electron diffraction and high-resolution
      transmission electron microscopy reveal the single-crystal nature of the Dy(OH)3
      and Dy2O3 nanotubes. The morphologies and crystalline structure of the as
      obtained products were characterized by scanning electron microscopy,
      transmission electron microscopy, and X-ray diffraction, respectively. By this
      method, we can obtain a mass of products.

PMID- 15853135
TI  - Oriented carbon nanostructures containing nitrogen obtained by ion beam assisted
      deposition.
AB  - In this paper, we report the deposition of graphite multilayer containing
      nitrogen covering nanometric nickel particles. In-situ photoelectron emission
      spectroscopy (XPS) reveals the presence of nitrogen in the carbon layer covering
      the nickel particles. The field emission properties of the structures are
      reported. Atomic force microscopy displays regular domelike structures. Raman
      spectroscopy shows the characteristic frequencies associated with graphite and
      disordered structures. High-resolution transmission electron microscopy confirms
      the presence of multiwall well-organized graphite layers covering the nickel
      particles. Disorder increases on increasing nitrogen content. The samples were
      prepared in-situ by depositing first a few atomic layers of nickel and subsequent
      islands formation by thermal annealing. Then, an argon ion beam bombards an
      ultrapure carbon target and simultaneously the growing film is assisted with a
      second low-energy nitrogen ion beam (ion beam assisted deposition).

PMID- 15853136
TI  - Metal-oxide-Semiconductor capacitors fabricated by layer-by-layer nanoassembly
      and microfabrication.
AB  - Metal oxide semiconductor (MOS) capacitors were fabricated by electrostatic layer
      by-layer self-assembly (LbL-SA) combined with a modified lift-off technique. The
      MOS capacitors were built on both n-type and p-type silicon substrates. The
      numbers of silicon dioxide (SiO2) nanoparticle layers were varied to characterize
      the electrical performance of MOS capacitors. Unlike the conventional process,
      LbL-SA allows us to deposit the thin films for a semiconductor device with a
      lower temperature, lower cost, and shorter processing time. The stability of the
      silica insulation layers was also investigated. Atomic force microscopy (AFM)
      served to monitor the film quality of the self-assembled thin films.

PMID- 15853137
TI  - Thermal stripping of supramolecular structures: C60 nanorods.
AB  - The investigated ionic C60 derivative self-assembles into nanorods. When the
      functional side groups are removed by heating the nanorods to 623 K, they retain
      their shape. Utilization of lithographic markers allows the study of identical
      nanostructures before and after heat treatment by dynamic mode atomic force
      microscopy. Various independent techniques, including Raman spectroscopy and mass
      spectroscopy demonstrate that the shape-preserving mechanism is a thermal
      stripping process, stabilizing the original supramolecular morphology. The latter
      implies two coherent sub-processes: detachment of the side groups and
      oligopolymerization running in parallel, eventually yielding rod-shaped C60
      polymers. Synthesizing fullerenic polymers in this way can lead to several
      applications.

PMID- 15853138
TI  - Determination of the diameter distribution of single-wall carbon nanotubes from
      the Raman G-band using an artificial neural network.
AB  - A novel, artificial neural network-based method is now available for obtaining
      the mean diameter of single wall carbon nanotube (SWCNT) samples from the
      diameter dispersive features of their Raman G-band. The method is demonstrated
      here for six different diameter SWCNT samples and 14 different excitation
      wavelengths. With an adequately large pool of standard nanotube samples, the
      suggested method is a useful complementary technique for SWCNT diameter analysis
      as it is capable of rapid diameter evaluation without prior knowledge of the
      relevant phonon dispersion relations.

PMID- 15853139
TI  - Resonance Raman spectroscopy characterization of single-wall carbon nanotube
      separation by their metallicity and diameter.
AB  - Several techniques were recently reported for the bulk separation of metallic (M)
      and semiconducting (S) single wall carbon nanotubes (SWNTs), using optical
      absorption and resonance Raman spectroscopy (RRS) as a proof of the separation.
      In the present work, we develop a method for the quantitative evaluation of the M
      to S separation ratio, and also for the SWNT diameter selectivity of the
      separation process, based on RRS. The relative changes in the integrated
      intensities of the radial-breathing mode (RBM) features, with respect to the
      starting material, yield the diameter probability distribution functions for M
      and S SWNTs in the separated fractions, accounting for the different resonance
      conditions of individual SWNTs, while the diameter distribution of the starting
      material is obtained following the fitting procedure developed by Kuzmany and
      coworkers. Features other than the RBM are generally less effective for
      characterization of the separation process for SWNTs.

PMID- 15853140
TI  - Evaporated nanostructured Y2O3:Eu thin films.
AB  - Europium-doped yttrium oxide (Y2O3:Eu) is a well-known luminescent material that
      in recent years has been studied in thin-film form. However, to date there has
      not been a great effort put into altering the nanostructure of these films. A
      thin-film deposition technique called glancing angle deposition allows for a high
      degree of control over the nanostructure of the thin film, resulting in thin
      films with nanostructure geometries ranging from chevron and post to helix.
      Glancing-angle deposition was used to make europium-doped yttrium oxide thin
      films with slanted-post nanostructures. Portions of the films were annealed in
      air at 850 degrees C for 10 hours following deposition. Scanning electron
      microscopy was used to characterize the nanostructures of the films, while UV
      laser excitation was used to characterize the photoluminescence properties of the
      films. The annealed samples exhibited increased photoluminescent responses
      compared to unannealed samples; however, the porous nanoscale geometry of the
      films was unaffected. In order to optimize the photoluminescence properties of
      the films, both the partial pressure of oxygen during film deposition and the
      level of europium doping in the source material used were varied. Films
      fabricated from the source material with a greater amount of europium doping had
      larger photoluminescent responses, while the optimal partial pressure of oxygen
      during electron-beam evaporation was found to be less than 1.0 x 10(-4) torr.

PMID- 15853141
TI  - Nanostructured antifouling poly(ethylene glycol) films for silicon-based
      microsystems.
AB  - The creation of antifouling surfaces is one of the major prerequisites for
      silicon-based micro-electrical-mechanical systems for biomedical and analytical
      applications (known as BioMEMS). Poly(ethylene glycol) (PEG), a water-soluble,
      nontoxic, and nonimmunogenic polymer has the unique ability to reduce nonspecific
      protein adsorption and cell adhesion and, therefore, is generally coupled with a
      wide variety of surfaces to improve their biocompatibility. To this end, we have
      analyzed PEG thin films of various grafting densities (i.e., number of PEG chains
      per unit area) coupled to silicon using a single-step PEG-silane coupling
      reaction scheme using variable-angle ellipsometry. Initial PEG concentration and
      coupling time were varied to attain different grafting densities. These data were
      theoretically analyzed to understand the phenomenon of PEG film formation.
      Furthermore, all the PEG films were evaluated for their ability to control
      biofouling using albumin and fibrinogen as the model proteins. PEG thin films
      formed by using higher PEG concentrations ( > or = 10 mM PEG) or coupling time (
      > or = 1 h) demonstrated enhanced protein fouling resistance behavior. This
      analysis is expected to be useful to form PEG films of desired grafting density
      on silicon substrates for appropriate application.

PMID- 15853142
TI  - Synthesis and antibacterial properties of silver nanoparticles.
AB  - Nanometer sized silver particles were synthesized by inert gas condensation and
      co-condensation techniques. Both techniques are based on the evaporation of a
      metal into an inert atmosphere with the subsequent cooling for the nucleation and
      growth of the nanoparticles. The antibacterial efficiency of the nanoparticles
      was investigated by introducing the particles into a media containing Escherichia
      coli. The antibacterial investigations were performed in solution and on petri
      dishes. The silver nanoparticles were found to exhibit antibacterial effects at
      low concentrations. The antibacterial properties were related to the total
      surface area of the nanoparticles. Smaller particles with a larger surface to
      volume ratio provided a more efficient means for antibacterial activity. The
      nanoparticles were found to be completely cytotoxic to E. coli for surface
      concentrations as low as 8 microg of Ag/cm2.

PMID- 15853143
TI  - Magnetic-field-sensing materials composed of metal-semiconductor hybrid
      nanostructures.
AB  - A huge positive magnetoresistance effect, about 4 orders of magnitude at room
      temperature, was discovered in metal-semiconductor hybrid nanostructures. The
      hybrid material consisting of metallic nanostructures that are fabricated on a
      GaAs substrate by ultra-high vacuum deposition method exhibits magnetic field
      sensitive current-voltage characteristics. When a constant voltage above the
      threshold value, is applied to the film, a very steep change in the current,
      which we term magnetoresistive switch, is driven by the huge magnetoresistance
      effect under a relatively low magnetic field at room temperature. The
      magnetoresistance effect is very sensitive to the nanoscale morphology of the
      hybrid film; in other words, one can control the magnetoresistance function at
      will by modifying the nanostructure of this material. The origin of the
      magnetoresistive switch effect and its possible application as a magnetic field
      sensor is discussed.

PMID- 15853144
TI  - Synthesis of SiC nanowires with in-situ deposition of carbon coating.
AB  - SiC nanowires are effective reinforcement materials in ceramic matrix composites.
      A compliant coating such as carbon on nanowires is necessary in order to moderate
      the nanowire/matrix interfacial bounding for taking the most advantages of SiC
      nanowires. SiC nanowires with an in-situ deposition of carbon shell coating were
      fabricated by a novel chemical vapor growth process. Highresolution transmission
      electron microscopy examinations showed that the nanowires consisted of a single
      crystal beta-SiC core with an amorphous carbon shell 2-5 nm in thickness. The
      nanowires were straight with a length generally over 10 microm and a diameter 15
      150 nm. The growth direction of the core SiC nanowires is (111). A simple three
      step growth model for SiC nanowires was proposed based on a vapor-solid growth
      mechanism. Because the carbon-coated nanowires were grown directly on continuous
      Tyranno-SA SiC fibers, in-situ application of the present technique on the
      fabrication of SiC nanowire-reinforced SiC/SiC composites is expected.

PMID- 15853145
TI  - Preparation of gold nanoparticles on silica substrate by radio frequency
      sputtering.
AB  - Radio frequency sputtering of gold on amorphous silica substrates was used for
      the preparation of Au nanoparticles on SiO2. Deposition experiments were carried
      out in Ar plasmas under mild conditions (RF power = 5/10 W, total pressure = 0.38
      mbar, substrate temperature < or = 210 degrees C), focusing in particular on the
      effect of sputtering time (5/30 min) and substrate temperature on gold nucleation
      and coalescence, with the aim of obtaining SiO2-supported Au nanoparticles
      characterized by precise structural and morphological features. To this aim,
      several analytical techniques were employed for a thorough characterization of
      the systems properties, including glancing incidence X-ray diffraction,
      transmission electron microscopy, X-ray photoelectron spectroscopy, atomic force
      microscopy, and UV-Vis absorption spectroscopy. In particular, the evolution of
      optical spectra, i.e., of the surface plasmon resonance peak, was used as a probe
      for the structural features and was related to the results obtained by other
      characterization techniques. Gold nanoclusters (phi approximately 4/10 nm)
      dispersed uniformly on silica matrices were obtained under soft conditions, with
      morphology ranging from island to cluster like. The obtained results make
      possible a careful modulation of substrate coverage and gold nanoparticle size.

PMID- 15853146
TI  - Synthesis of solvent-stabilized colloidal nanoparticles of platinum, rhodium, and
      ruthenium by microwave-polyol process.
AB  - Solvent-stabilized Pt, Rh, and Ru colloidal nanoparticles were synthesized by a
      microwave-polyol process. They were characterized by TEM and XPS, XRD, and UV-vis
      examination. These colloids have small particle sizes with narrow size
      distribution, and they were stable in glycol upon storage under ambient condition
      for months. Separation and XPS characterization of the intermediate colloids
      demonstrated the two-step mechanism for the formation of solvent-stabilized metal
      colloids via hydrolysis.

PMID- 15853147
TI  - Fabrication of highly efficient full-color electroluminescent device composed of
      nanocrystalline silicon.
AB  - We fabricated a highly-efficient full-color electroluminescent device composed of
      nanocrystalline silicon (nc-Si). High luminance red, green and blue luminescence
      from the device was achieved by using hydrofluoric acid solution and oxidation
      techniques, because these techniques lead to reduction of both nc-Si size and
      P(b)-center on the surface, which is related closely to luminescent color and
      luminance, respectively. Moreover, direct current (DC) operating voltage on
      red/green/blue light emission of the device was realized at a relative low value
      below 10.0 V by controlling the thickness of the oxidized layer on the nc-Si
      surface. These results are a strong indication that the device developed in this
      study can be adapted to future flat panel display and illumination fields.

PMID- 15853148
TI  - Highly ordered carbon nanotubes based on porous aluminum oxide: fabrication and
      mechanism.
AB  - Highly ordered carbon nanotubes (CNTs) are wildly pursued due to their unique
      properties. Anodic aluminum oxide (AAO) exhibits great possibility for this
      purpose. Here, CNTs based on AAO template were produced using acetylene or
      ethylene as the hydrocarbon sources with or without the presence of Co catalysts.
      CNTs grown on the Co-embedded AAO samples were normally confined within the
      nanopores of the AAO template. It was found that C2H4 normally requires 100
      degrees C higher pyrolysis temperature than C2H2 under otherwise identical
      conditions. The pyrolysis temperature is greatly reduced with the presence of Co
      catalysts. CNTs can grow out of the nanopores, if Co particles are present at the
      bottom of the nanopores and if the nanopores are short in length or large in
      diameter. The graphitization of AAO template grown CNTs was studied by Raman
      spectroscopy. The CNTs produced from ethylene are generally better in
      graphitization than those from acetylene, and the CNTs grown with the presence of
      Co catalysts deposited at the bottom of nanopores are better than those without
      Co catalysts or with Co catalysts coated on the entire inner wall of nanopores.
      The growth temperature is found not to play a critical role in graphitization.

PMID- 15853149
TI  - Novel single-phase and gram-scale synthesis of thiol-uncapped stable colloidal
      gold nanoparticles.
AB  - Here we describe a new chemical route for obtaining nanometer-sized gold(0)
      particles with a narrow size distribution and a band gap of 1.45 eV. The
      synthetic method is based on the reduction of AuBr3 with t-BuOLi activated LiH in
      dioxane. The single-phase process developed allows the production of large
      quantities of stable thiol-uncapped gold(0) nanoparticles. These clusters were
      further used for the production of monodisperse Au nanoparticles with controlled
      surface properties through ligand exchange with 1-dodecanethiol or 1-decylamine.

PMID- 15853150
TI  - Application of the Taguchi analytical method for optimization of effective
      parameters of the chemical vapor deposition process controlling the production of
      nanotubes/nanobeads.
AB  - Seven variable parameters of the chemical vapor deposition system have been
      optimized with the help of the Taguchi analytical method for getting a desired
      product, e.g., carbon nanotubes or carbon nanobeads. It is observed that almost
      all selected parameters influence the growth of carbon nanotubes. However, among
      them, the nature of precursor (racemic, R or Technical grade camphor) and the
      carrier gas (hydrogen, argon and mixture of argon/hydrogen) seem to be more
      important parameters affecting the growth of carbon nanotubes. Whereas, for the
      growth of nanobeads, out of seven parameters, only two, i.e., catalyst (powder of
      iron, cobalt, and nickel) and temperature (1023 K, 1123 K, and 1273 K), are the
      most influential parameters. Systematic defects or islands on the substrate
      surface enhance nucleation of novel carbon materials. Quantitative contributions
      of process parameters as well as optimum factor levels are obtained by performing
      analysis of variance (ANOVA) and analysis of mean (ANOM), respectively.

PMID- 15853151
TI  - Synthesis and characterization of superconducting nanocrystalline niobium
      nitride.
AB  - Nanocrystalline niobium nitride (NbN0.9) was successfully synthesized at 600
      degrees C through a solid-state reaction. The synthesis was carried out in an
      autoclave by using NbCl5 and NaN3 as the reactants. The X-ray powder diffraction
      pattern indicates the formation of cubic NbN0.9. Transmission electron microscopy
      images show that typical NbN0.9 crystallites are composed of uniform particles
      with an average size of about 30 nm and nanorod crystallites with a typical size
      of about 40 x 2500 nm. Magnetic measurements exhibited that a superconducting
      transition occurred at 15.4 K for the NbN0.9 product.

PMID- 15853152
TI  - CdS nanoparticles grown in a polymer matrix by chemical bath deposition.
AB  - Nanocrystallites of CdS have been grown by chemical bath deposition within the
      pores of poly(vinyl alcohol) (PVA) on glass and Si substrates. The CdS-PVA
      composite films are transparent in the visible region. XRD and TEM diffraction
      patterns confirmed the nanocrystalline CdS phase formation. TEM study of the film
      revealed the manifestation of nano CdS phase formation and the average particles
      size was varied in the range 5-12 nm. UV-vis spectrophotometric measurement
      showed high transparency (nearly 80% in the wavelength range 550-900 nm) of the
      films with a direct allowed band gap lying in the range 2.64-3.25 eV. Particle
      sizes have also been calculated from the shift of band gap with respect to that
      of bulk value and were found to be in the range 3.3-6.44 nm. The high dielectric
      constant (lies in the range 120-250 at high frequency) of PVA/CdS nanocomposite
      compared to that of pure PVA (-28) has been observed. The dielectric constant
      decreases with increase of dispersibility of the CdS nanoparticles within PVA.
      The nanocrystalline PVA/CdS thin films have also showed field emission properties
      with a turn-on field of approximately 6.6 V/microm, whereas only PVA thin film
      and bulk CdS on PVA have shown no field emission.

PMID- 15853154
TI  - Electric field-assisted deposition of nanowires on carbon nanotubes for
      nanoelectronics and sensor applications.
AB  - Manipulation and control of matter at the nanoscale and atomic scale levels are
      crucial for the success of nanoscale sensors and actuators. The ability to
      control and synthesize multilayer structures using carbon nanotubes that will
      enable the building of electronic devices within a nanotube is still in its
      infancy. In this paper, we present results on selective electric field-assisted
      deposition of metals on carbon nanotubes realizing metallic nanowire structures.
      Silver and platinum nanowires have been fabricated using this approach for their
      applications in chemical sensing as catalytic materials to sniff toxic agents and
      in the area of biomedical nanotechnology for construction of artificial muscles.
      Electric field-assisted deposition allows the deposition of metals with a high
      degree of selectivity on carbon nanotubes by manipulating the charges on the
      surface of the nanotubes and forming electrostatic double-layer supercapacitors.
      Deposition of metals primarily occurred due to electrochemical reduction,
      electrophoresis, and electro-osmosis inside the walls of the nanotube. SEM and
      TEM investigations revealed silver and platinum nanowires between 10 nm and 100
      nm in diameter. The present technique is versatile and enables the fabrication of
      a host of different types of metallic and semiconducting nanowires using carbon
      nanotube templates for nanoelectronics and a myriad of sensor applications.

PMID- 15853153
TI  - Formation of Au nanostructures through an alumina mask by laser-assisted
      deposition.
AB  - We report a new method to produce ordered arrays of metal nanostructures on
      substrates. The method employs a through-hole nanoporous alumina membrane as a
      mask that is attached onto the substrate, silicon in this study. The material of
      deposition, Au in this study, was provided by pulsed laser ablation of a target
      gold. At an early stage of the deposition, a significant portion of Au penetrated
      the alumina through-holes and formed an ordered nanodot array on the silicon
      surface. At the later stage, the through-hole deposition was blocked by the
      growth of Au film on the top surface of the alumina, so that the heights of the
      Au nanodots were limited to about 10 nm under current experimental conditions.
      Subsequent attempts to clean up the top surface of the alumina with a lower power
      laser illumination resulted in the formation of new nanostructures around the
      alumina pores, nanospheres, or nanorings, depending on the fluence of the laser
      and the duration of the cleanup. We will discuss the underlying mechanism of the
      formation of these nanostructures.

PMID- 15853155
TI  - Visualizing adhesion-induced agglutination of Escherichia coli with mannosylated
      nanoparticles.
AB  - Polymeric nanoparticles covalently functionalized with derivatized D-mannose
      molecules were synthesized and characterized. These nanoparticles have an average
      size of approximately 160 nm in diameter, thus bearing a large number of surface
      tethered mannose moieties for multivalent interactions with adhesins on bacterial
      cells. Specifically, the mannosylated nanoparticles bind strongly with
      Escherichia coli, allowing the convenient visualization of adhesion interactions
      under a conventional electron microscope. Since a single nanoparticle is capable
      of binding more than one cell, the adhesion interactions result in significant
      nanoparticle-mediated cell agglutination according to electron microscopy
      imaging. Potential applications of the mannosylated nanoparticles in the
      inhibition of enteropathogenic infections are discussed.

PMID- 15853156
TI  - Nanoalloys based on clays: intercalated semicrystalline blends of syndiotactic
      polystyrene with poly(2,6-dimethyl-p-phenylene oxide).
AB  - Nanoalloys of syndiotactic polystyrene with poly(2,6-dimethyl-p-phenylene oxide)
      clay were prepared by a solution intercalation technique using 1,1,2,2
      tetrachloroethane. A mixed intercalated/exfoliated morphology in the nanoalloys
      containing organo-clays is evinced by transmission electron microscopy. Thermal
      stability is found to improve with 5% by weight of organo-clays, but a reverse
      trend is observed by increasing the concentration of clay. The influence of
      montmorillonite clays in isothermal melt-crystallization behavior of blends was
      thoroughly investigated by using differential scanning calorimetry and wide-angle
      X-ray diffraction. A considerable change in polymorphic behavior of syndiotactic
      polystyrene is observed by the incorporation of different clays into the blends,
      and the temperature window of isothermal crystallization for the formation of a
      crystals of syndiotactic polystyrene is found to broaden in the presence of
      organo-clays. In contrast, the pristine clay is found to induce only the beta
      crystal of syndiotactic polystyrene at all the crystallization temperatures
      studied in this work. The amorphous component poly(2,6-dimethyl-p-phenylene
      oxide) affects the crystallinity of syndiotactic polystyrene adversely and favors
      the beta-form of syndiotactic polystyrene in blends; a-crystals are observed in
      the nano-alloys containing 20 wt% of poly(2,6-dimethyl-p-phenylene oxide). The
      crystalline morphology, as characterized by polarized optical microscopy, clearly
      indicates rapid formation of the alpha-form induced by the nanoscale dispersion
      of organo-clays in spherulites of smaller dimension.

PMID- 15853157
TI  - Microscopy and quantitative morphology of aluminum silicate nanoparticles grown
      on organic templates.
AB  - Biomimetic synthesis of ceramic materials is increasing in popularity because it
      offers many advantages. In this work, aluminum silicate nanoparticles were
      obtained on a self-assembled organic multilayer at near room temperature (30 < or
      = T < or = 50 degrees C) and at atmospheric pressure. Morphological and
      microanalytical characterization was carried out by means of transmission
      electron microscopy and subsequent image analysis. The roles of some process
      parameters such as template type, reactant concentration, [Al]:[Si] molar ratio,
      number of initiation steps (IS) of mineralization, and reaction time (rt) were
      assessed by comparing images, diffraction patterns, and EDX spectra. Generally,
      the Si-rich phase exhibited higher crystallinity, whereas the Al-rich phase was
      mostly amorphous. Crystal structure resulted with rt > or = 4 days for template
      grown materials. Images of materials obtained at T = 50 degrees C, rt = 3 days,
      and 1 < or = IS < or = 4 were further analyzed by "spectrum enhancement," an
      algorithm based on the Fourier transform. Morphological indicators were extracted
      from suitably processed power spectral densities, a correlation matrix was
      formed, and multivariate statistics was carried out. Visual differences in
      nanoaggregate morphology were quantitatively translated. Materials were ranked by
      the spatial uniformity of nanoparticle distribution: the most uniform aggregates
      were those grown on templates by IS > or = 2. Univariate statistics validated the
      conclusion: the particles of those same materials had a narrower size
      distribution and sharper edges. This last property has been ascribed to
      crystalline structure, independently demonstrated by diffraction patterns.

PMID- 15853158
TI  - A nurse's responsibility.

PMID- 15853159
TI  - Graft failure following allogeneic blood and marrow transplant: evidence-based
      nursing case study review.
AB  - Despite the advances made since the earliest days of transplant therapy, graft
      failure following allogeneic blood and marrow transplant is still a life
      threatening complication. This article reviews the science of graft failure and
      uses a case study presentation to address how an oncology nursing staff was
      motivated by a patient's experience of graft failure. An evidence-based
      literature review was undertaken to answer three relevant clinical questions: (a)
      What factors contribute to graft failure in patients receiving allogeneic
      hematopoietic stem cell transplants? (b) What interventions are appropriate for
      these patients? and (c) How can this information assist nursing staff in
      providing improved care for these patients? An example of the table of evidence
      is provided.

PMID- 15853160
TI  - Nursing implications of imatinib as molecularly targeted therapy for
      gastrointestinal stromal tumors.
AB  - Gastrointestinal stromal tumor (GIST), a form of soft-tissue sarcoma, is the most
      common noncarcinomatous tumor of the gastrointestinal tract. Despite its high
      incidence of recurrence, the malignant potential of GIST has been under
      recognized. Advances in diagnostic technology since 2000 have led to increased
      diagnoses of GIST, suggesting that GIST is more common than previously suspected.
      Historically, the only treatment for GIST was surgical resection, but recent
      advances in the understanding of the pathogenesis of the disease have led to the
      development of a new treatment. A key factor in the growth and survival of
      cancerous GIST cells is the uncontrolled activation of a signaling enzyme known
      as KIT, a receptor tyrosine kinase, which becomes locked in an activated state.
      The abnormal signaling from the overactive KIT enzyme causes GIST cells to
      survive and proliferate uncontrollably. Imatinib mesylate is an oral drug
      designed to inhibit the kinase enzyme activity of KIT. Imatinib has been proven
      in several clinical trials to be effective against GIST and is currently the
      firstline medical therapy for malignant metastatic or recurrent GIST. Imatinib is
      administered as an outpatient oral drug and warrants nursing management with
      particular attention to potential side effects, significant drug interactions,
      monitoring, and patient education. This article--based on published trials and
      clinical experience--summarizes the nursing implications, clinical efficacy, and
      safety of imatinib as an effective and rationally targeted treatment for GIST.

PMID- 15853161
TI  - Interventions to prevent loss of bone mineral density in women receiving
      chemotherapy for breast cancer.
AB  - Loss of bone mineral density (BMD) is a significant problem for women receiving
      breast cancer treatment. The purpose of this article is to present the state of
      the knowledge on BMD loss and analyze interventions to prevent BMD loss in women
      receiving breast cancer treatment. The data sources include primary research
      reports, review articles, and book chapters. With increased numbers of breast
      cancer survivors, BMD loss experienced with treatment is a significanthealth
      concern because of risks of osteoporosis and bone fractures. These long-term
      treatment effects may significantly impact patients' long-term morbitity and
      mortality. BMD screening as well as an assessment of physical activity and
      dietary history should be conducted with women undergoing breast cancer
      treatment. Bisphosphonates are effective in preventing BMD loss, and other
      interventions such as physical activity and dietary interventions need further
      testing. Oncology nurses are ideal candidates for implementing interventions to
      prevent BMD loss because of their understanding of cancer treatments, knowledge
      of health-related behaviors, and ability to teach patients about the positive
      health benefits of lifestyle changes.

PMID- 15853162
TI  - Case report: painful peripheral neuropathy following treatment with docetaxel for
      breast cancer.
AB  - Peripheral neuropathy is a common side effect of many chemotherapy agents. As
      many as 60% of patients receiving taxane therapy report symptoms such as
      numbness, tingling, burning, pain, and, in severe cases, weakness in a stocking
      and glove pattern. These symptoms are associated with problems in physical
      mobility and decreased quality of life, yet few articles in the literature
      discuss collaborative interdisciplinary assessment and treatment of this
      population. This article describes the care of a patient with diabetes and
      docetaxel-induced, painful peripheral neuropathy by a multidisciplinary team of
      nurses, physicians, and physical therapists. Because nurses are often the first
      clinicians to recognize symptoms of chemotherapy-induced peripheral neuropathy,
      they provide the essential coordination of care by appropriate medical and
      rehabilitative services. This case also raises important questions about the
      relationship between diabetes mellitus and persistent, painful peripheral
      neuropathy.

PMID- 15853163
TI  - Ten simple strategies to prevent chemotherapy errors.
AB  - Safety experts currently recommend using technology to prevent medication errors.
      Computerized prescriber order entry, automated medication-dispensing machines,
      and bar coding are a few of the technologies being advocated to promote safety.
      Simple, easily implemented safety strategies to prevent chemotherapy errors
      should not be overlooked and include consistent use of a reliable method to
      verify patient identity, metric measurement, and workplace illumination and
      organization. Other strategies are elimination of abbreviations and acronyms,
      provision of up-to-date information at the point of care, and partnering with
      patients for safety. These strategies can be customized for use in a variety of
      practice settings. Oncology nurses are at the forefront of chemotherapy error
      prevention initiatives and play a key role in implementing safety measures.

PMID- 15853164
TI  - The impact of humor on patients with cancer.
AB  - Using the Stetler model, in-depth literature reviews were performed that
      demonstrated a positive correlation between humor and comfort levels in patients
      with cancer. Humor frequently was used for relaxation and as a coping mechanism
      that aided in promoting general wellness. The literature indicated that various
      types of humorous material lessened anxiety and discomfort, which allowed for
      patients' concerns and fears to be discussed openly. The literature also showed
      that humor had a positive effect on the immune system. Improvements in pain
      thresholds and elevations in natural killer cell activity consistently appeared
      in quantitative experimental studies. In addition, measurements of specific
      neuroendocrine and stress hormone levels revealed biochemical changes that
      suggested improved physical stress responses and increased feelings of well-being
      after humorous interventions. This article has implications for nurses because
      humor can be an effective intervention that impacts the health and well-being of
      patients with cancer.

PMID- 15853165
TI  - Staying focused with a changing career focus.

PMID- 15853166
TI  - Reading a research article part II: parametric and nonparametric statistics.
AB  - Researchers often try to use a randomization technique in an attempt to reduce
      bias and ensure that treatment and control groups are as similar as possible.
      This article has provided an overview of how researchers might use parametric and
      nonparametric statistics when analyzing data and looking for differences between
      groups. Researchers must consider the types of data and choose the tests that are
      appropriate for the variable types to draw appropriate conclusions. The next
      article in this series will address comparison of more than two groups and
      repeated measures and other design issues.

PMID- 15853167
TI  - Complementary and alternative medicine patients are talking about: lycopene.

PMID- 15853168
TI  - Endometrial cancer and tamoxifen.

PMID- 15853169
TI  - Magnetic resonance imaging: a view from the inside.

PMID- 15853170
TI  - Novel breast-imaging methods.

PMID- 15853171
TI  - Chemotherapy-induced nausea and vomiting.

PMID- 15853172
TI  - Osteoporosis in the oncology setting.

PMID- 15853173
TI  - A pharmacologic overview of current and emerging anticoagulants.
AB  - For over 50 years, anticoagulant options for the treatment and prevention of
      thrombosis have been limited mainly to traditional agents such as unfractionated
      heparin and oral vitamin K antagonists such as warfarin. These traditional agents
      are fraught with limitations that complicate their clinical use. A variety of
      novel anticoagulants with improved pharmacologic and clinical profiles have
      recently been introduced or are in development, offering benefits over
      traditional therapies. Specifically, progress has been made in the development of
      low-molecular-weight heparins, factor Xa inhibitors, and direct thrombin
      inhibitors. Because of their convenience and ease of use, some of these novel
      compounds are competing with the traditional anticoagulants and are needed
      additions to the antithrombotic arsenal.

PMID- 15853174
TI  - Prevention of venous thromboembolism in medical and surgical patients.
AB  - Prophylaxis against venous thromboembolism (VTE) should be considered in all
      hospitalized patients, as VTE is a significant cause of morbidity and mortality
      in the hospital. Although VTE risk is greatest and VTE prophylaxis is more
      established in surgical patients, most hospitalized medical patients have one or
      more risk factors for VTE and are candidates for prophylaxis. Selection of a
      prophylaxis strategy should be guided by the patient's risk factors for VTE and
      the risks associated with prophylaxis options. This review surveys evidence and
      recommendations for various VTE prophylaxis methods in medical and surgical
      patients.

PMID- 15853175
TI  - Current and emerging options in the management of venous thromboembolism.
AB  - Venous thromboembolism (VTE) is a common disease whose diagnosis is challenging.
      The best diagnostic approaches combine the patient's pretest clinical probability
      of disease with D-dimer testing and/or diagnostic imaging. In light of several
      advantages, low-molecular-weight heparins are now recommended over unfractionated
      heparin for most patients with acute VTE. Newer anticoagulants such as the factor
      Xa inhibitor fondaparinux also show promise for acute VTE. For chronic
      management, the duration and intensity of warfarin therapy should be tailored to
      the individual patient.

PMID- 15853176
TI  - Stroke prevention in atrial fibrillation: current anticoagulation management and
      future directions.
AB  - Atrial fibrillation (AF) is an important cause of stroke, and stroke risk
      stratification is critical to the management of patients with AF. Anticoagulation
      with warfarin is the current standard of care for stroke prevention in these
      patients, despite the need for close monitoring. Aspirin alone is not as
      effective. Warfarin is recommended for patients with AF and valvular disease or
      with AF and one or more stroke risk factors. Other novel anticoagulants and
      antiplatelet combinations are under investigation. Curative procedures for AF are
      possible, but their long-term safety and effect on stroke risk are unknown.

PMID- 15853177
TI  - Heparin-induced thrombocytopenia: principles for early recognition and
      management.
AB  - Heparin-induced thrombocytopenia (HIT) is a potentially devastating complication
      of therapy with either unfractionated or low-molecular-weight heparin.
      Thrombocytopenia is no longer essential for the diagnosis of HIT, since a 50%
      drop in the platelet count may be a more specific indicator. Once HIT is
      clinically suspected, heparin should be stopped immediately and direct thrombin
      inhibitor therapy started; waiting for laboratory confirmation may be
      catastrophic.

PMID- 15853178
TI  - Anticoagulation in special patient populations: are special dosing considerations
      required?
AB  - Optimal dosing of low-molecular-weight heparin (LMWH) therapy has not yet been
      established for patients with morbid obesity or renal insufficiency or for
      pregnant women. Monitoring of anti-Xa levels appears to be helpful in guiding
      LMWH dosing in all of these patient groups. Use of fondaparinux in these
      populations has yet to be defined. Cancer patients are at particular risk of
      venous thromboembolism and generally require escalated and/or prolonged
      anticoagulation with intense monitoring of therapy.

PMID- 15853180
TI  - A winter day in Rowan County.

PMID- 15853179
TI  - Cost considerations surrounding current and future anticoagulant therapies.
AB  - Because the costs of anticoagulation therapy are substantial and the difference
      between the risks and benefits of this therapy are often narrow, economic
      analyses are particularly valuable when weighing anticoagulation options.
      Economic analyses to date suggest that anticoagulation is most effective and
      results in the greatest cost savings when applied to populations at highest risk
      for thrombotic events. They also suggest that in situations where a more costly
      anticoagulant agent is available, that agent is cost-effective only if it is
      clearly more efficacious or if it substantially reduces costs in other areas,
      such as hospitalization. These principles should guide clinicians' choices of
      anticoagulation strategies.

PMID- 15853181
TI  - Inhaled nitric oxide in the treatment of persistent pulmonary hypertension/
      hypoxic respiratory failure in neonates: an update.
AB  - Persistent pulmonary hypertension (PPHN) and subsequent hypoxic respiratory
      failure is seen in association with numerous diseases and conditions in the
      neonate. This includes infections such as group B streptococcus, meconium
      aspiration syndrome, perinatal asphyxia, congenital diaphragmatic hernia,
      congenital heart disease, and as an idiopathic phenomenon. Conventional therapy
      of persistent pulmonary hypertension is discussed, as well as integrated with
      current treatment modalities such as surfactant replacement therapy and high
      frequency ventilation. The molecular action of nitric oxide including its
      relationship to neonatal cardiopulmonary transition at birth and the human
      neonatal clinical experience with term infants from 1992 to the present is
      explored. Also, the current use of inhaled nitric oxide in preterm infants is
      reviewed. Additionally, the follow-up of infants treated with inhaled nitric
      oxide is summarized, and novel therapies including inhaled prostacyclin and other
      pulmonary vasodilators such as sildenafil are introduced.

PMID- 15853182
TI  - The many faces of hypothyroidism: a review of two inpatient populations.
AB  - Unusual presentations of acute hypothyroidism often go unrecognized and delay the
      onset of effective therapy. We reviewed admissions of two different patient
      populations at the University of Louisville Hospital and the Veterans Affairs
      Medical Center to evaluate the extent and profiles of such patients admitted for
      acute care. We found that although these hospitals differed in gender and age
      profiles, similarities existed for their admissions and delay in diagnosis for
      hypothyroidism. These similarities were related to unusual clinical presentation
      including myxedematous states, which were not usually recognized, and psychiatric
      conditions that were also commonly complicated by hypothyroidism. In all cases,
      the history, physical examinations, and thyroid-stimulating hormone test were
      essential in recognizing acute hypothyroidism so as to institute effective
      therapy with thyroid replacement early in the course of the disorder.

PMID- 15853183
TI  - The physician's duty and role in communicating with family members regarding
      results of patients' genetic testing.

PMID- 15853184
TI  - Succession planning.

PMID- 15853185
TI  - A cancer clip.

PMID- 15853186
TI  - Bush plan takes security out of social security.

PMID- 15853187
TI  - Is there a global common core to social work? A cross-national comparative study
      of BSW graduate students.
AB  - This article reports findings from a cross-national comparative study that
      examined the commonalities and differences in professional ideology among social
      work graduates in 10 countries by studying their attitudes toward poverty and the
      goals of social work. The major finding is the substantial similarity in the
      students' professional ideology despite the different contexts of their
      professional socialization process. Students in all the countries attributed
      poverty to structural causes and supported the extension of state social welfare
      as a way of dealing with poverty. They expressed a large degree of support for
      individual well-being and social justice as major goals of social work.
      Differences were also identified. The similarities and differences reflect the
      interplay of centrifugal and centripetal forces that fashion the characteristics
      of global social work.

PMID- 15853188
TI  - The influence of Sekentei on family caregiving and underutilization of social
      services among Japanese caregivers.
AB  - The Asian family is regarded as a close-knit social unit in which elderly people
      are believed to occupy a highly respected position. Family members are thought to
      provide care for elderly parents gratefully because of filial piety. This
      stereotypic portrayal of Asian families, however, may not apply fully to Japanese
      families. This article points out misunderstandings and stereotypic views of
      family caregiving of Japanese elderly people. The article describes how the
      cultural virtue of filial piety has been incorrectly identified as the major
      factor influencing underutilization of social services among Japanese family
      caregivers. The authors provide new insights into Japanese family caregiving by
      describing the concept of sekentei and how this concept may influence family
      caregiving of elderly family members and underutilization of social services
      among Japanese caregivers.

PMID- 15853189
TI  - Bioterrorism and smallpox: policies, practices, and implications for social work.
AB  - Terrorist acts and the fear of terrorism have become a part of everyday life in
      the early 21st century. Among the threats most feared is bioterrorism, including
      the intentional release of smallpox. With the invasion of Iraq and toppling of
      the Saddam Hussein regime, acute bioterrorism fears have abated; however, an
      ongoing threat remains.This article addresses the need for knowledge and rational
      policies in dealing with potential bioterrorism attacks. It presents information
      on four of the most likely bioterrorism agents: smallpox, anthrax, botulism, and
      plague. It illustrates the importance of accurate knowledge and rational decision
      making in addressing the threat of terrorism through the intentional release of
      biological weapons such as smallpox. Finally, it provides information essential
      for social workers to make informed practice decisions, to educate clients and
      the public, and to advocate for sound public policy.

PMID- 15853190
TI  - American Indian/Alaskan Native grandparents raising grandchildren: findings from
      the Census 2000 Supplementary Survey.
AB  - This article documents the prevalence and national profile of American
      Indian/Alaskan Native (AI/AN) grandparents who are raising their grandchildren,
      based on data from the American Community Survey/Census 2000 Supplementary
      Survey. In 2000 there were estimated to be nearly 53,000 AI/AN grandparent
      caregivers age 45 and older in the United States. Almost half of the caregiving
      grandparents had been raising a grandchild for five years or longer. The findings
      reveal a portrait of grandparents committed to raising their grandchildren
      despite the fact that many were living in extreme poverty, with ill health, and
      with limited resources and services. One-third of grandparent caregivers were
      living below the poverty line, and only one-quarter of these were receiving
      public assistance. Even when compared with their noncaregiving AI/AN peers,
      grandparents raising grandchildren were disproportionately female, poor, living
      with a functional disability, and living in overcrowded conditions. Implications
      for social work practice are presented and recommendations for policy and
      research are discussed.

PMID- 15853191
TI  - The role of the social worker in the face of terrorism: Israeli community-based
      experience.
AB  - Terrorism and its aftermath have become part of the Western way of life, and
      social workers have a central role to play in helping affected families and their
      communities. Drawing on community-based experience in Israeli communities, the
      authors examine the planning of multidisciplinary teams and how their planning
      was put into effect in their communities in several terrorist attacks. The
      authors use reports of social workers, community volunteers, and clients to map
      the phases of the activity, the roles and goals of the social workers with
      different focal systems during the phase stages, and the tasks that the social
      workers carried out.

PMID- 15853192
TI  - Social work in Jewish community centers: a question of compatibility.
AB  - This article focuses on the Jewish community center JCC) as a host setting for
      social work practice. Findings of a national study of JCC professional staff
      designed to explore the degree of congruence between social work values and JCC
      practice are presented. The findings have implications for other sectarian and
      nonsectarian host settings providing similar types of services. The survey was
      sent to practitioners at 191 of 200 JCCs. The sample was drawn from a population
      of MSW and non-MSW personnel. Respondents were asked to indicate the extent to
      which they fulfilled particular social work responsibilities. One-way analysis of
      variance (ANOVA) and the independent t tests were used to analyze the data. The
      study findings demonstrate that social workers actively call on their knowledge,
      values, and skills, deal with the social welfare concerns of constituents, and
      use the agencies' Jewish function as a guide for their practice.

PMID- 15853193
TI  - Social work and the house of Islam: orienting practitioners to the beliefs and
      values of Muslims in the United States.
AB  - Despite the media attention focused on the Islamic community after the terrorist
      attacks on the World Trade Center on September 11, 2001, Muslims remain one of
      the most misunderstood populations in the United States. Few articles have
      appeared in the social work literature orienting practitioners to the Islamic
      community, and much of the mainstream media coverage misrepresents the
      population. This article reviews the basic beliefs, practices, and values that
      commonly characterize, or inform, the House of Islam in the United States. The
      organizations that embody and sustain the Muslim communities that constitute the
      House of Islam are profiled, and areas of possible value conflicts are examined.
      The article concludes by offering suggestions for integrating the article's
      themes into practice settings. Particular attention is given to enhancing
      cultural competence and to suggestions for spiritual assessment and
      interventions.

PMID- 15853194
TI  - The largely untold story of welfare reform and the human services.
AB  - Welfare reform has placed the lives of clients, the jobs of social workers, and
      the mission of agencies in jeopardy. Based on interviews with senior staff at 107
      nonprofit human services agencies, this article documents the largely untold
      story of how nonprofit agencies' workers responded to the impact of welfare
      reform on their clients, their jobs, and the delivery of services. Workers
      reported less time for social services because of welfare-related regulations,
      penalties, work mandates, crises, and paper work. They also reported more service
      dilemmas including less control of the job, more ethical conflicts, less
      efficacy, and increased burn-out. Even so, workers felt that they were making a
      difference, and agencies indicated increased advocacy. Relying heavily on the
      voice of social workers, the article illuminates the experiences and feelings of
      agency staff as they try to do their best for clients in difficult times.

PMID- 15853195
TI  - Pet loss: implications for social work practice.

PMID- 15853196
TI  - National Hospital Discharge Survey: 2002 annual summary with detailed diagnosis
      and procedure data.
AB  - OBJECTIVES: This report presents 2002 national estimates and selected trend data
      on the use of non-Federal short-stay hospitals in the United States. Estimates
      are provided by selected patient and hospital characteristics, diagnoses, and
      surgical and nonsurgical procedures performed. Estimates of diagnoses and
      procedures are presented according to International Classification of Diseases,
      9th Revision, Clinical Modification (ICD-9-CM) codes. METHODS: The estimates are
      based on data collected through the National Hospital Discharge Survey (NHDS).
      The survey has been conducted annually since 1965. In 2002, data were collected
      for approximately 327,000 discharges. Of the 474 eligible non-Federal short-stay
      hospitals in the sample, 445 (94 percent) responded to the survey. RESULTS: An
      estimated 33.7 million inpatients were discharged from non-Federal short-stay
      hospitals in 2002. They used 164.2 million days of care and had an average length
      of stay of 4.9 days. Common first-listed discharge diagnoses included delivery,
      ischemic heart disease, psychoses, pneumonia, and malignant neoplasms. Inpatients
      had 6.8 million cardiovascular procedures and 6.6 million obstetric procedures.
      Males had higher rates for cardiac procedures such as cardiac catheterization and
      coronary artery bypass graft, but males and females had similar rates of
      pacemaker procedures. The number and rate of all cesarean deliveries, primary and
      repeat, rose from 1995 to 2002; the rate of vaginal birth after cesarean delivery
      dropped from 35.5 in 1995 to 15.8 in 2002.

PMID- 15853197
TI  - [Corrosion study of anodically and thermically surface-treated osteosynthesis
      plates].
AB  - For the fixation of mandibular fractures, at the Department of Oral Surgery and
      Dentistry at Semmelweis University, anodically and thermically treated TiO2/Ti
      osteosynthesis plates are used. The corrosion studies were performed in a
      generally-applied 3-electrode electrochemical measurement cell, with a calomel
      electrode as reference electrode, and a Pt net as conducting electrode. The
      cyclic voltammetric measurements demonstrated that the pore-free surface TiO2
      layer forms a highly protective barrier on the surface of Ti. The electrochemical
      impedance spectrum reflected a decrease in inhomogeneity of the sample because of
      a decrease in the number of pinholes. Such a change is indicative of passivation.
      The reported techniques appear to comprise a reliable method of study for an
      evaluation of the long-term corrosion behaviour of implants.

PMID- 15853198
TI  - [Background data about the dental fear scores of Hungarian secondary school
      students].
AB  - Free association (coupling) of 139 Hungarian secondary school students (90
      females, 49 males, age between 14-18 yr.) about their teeth was collected. Dental
      fear (DAS, DFS) and general anxiety scores were measured. Typical dental events
      (i.e.: simple and traumatising dental treatments, etc.) were coupled by the
      participants in 36,7% of the cases. Functions and importance of the teeth and
      oral hygiene were described in 7,2% of the cases. Simple, grotesque, or magical
      stories and tales about teeth were found in 16,5% of the cases. No answer was
      found in 39,6% of the cases. Highest dental fear and general anxiety scores were
      found in the group coupled traumatising dental treatment. Age had no influence on
      the sense of the association (coupling).

PMID- 15853199
TI  - [The effectiveness of a benzydamine rinse in the management of stomato
      glossopyrosis].
AB  - Burning mouth syndrome (BMS) is a frequent source of oral discomfort and
      sensation mainly at middle-aged or elderly women without identifiable local
      pathology. Forty-two patients with stomato-glossopyrosis were registered at the
      Department of Periodontology, Dental School, University Pecs, between August 2002
      and January 2003. Oral clinical examination failed to identify physical
      explanation for the complaint of painful or burning mouth. After complete
      examination (blood test included), scaling, root planning and oral hygiene
      instructions were given. Six patients reported decreasing mucosal pain or
      burning. Two patients had iron-deficiency and Sjogren's syndrome was suspected
      and verified at another two patients. Thirty-two patients completed the
      benzydamine-study. They were divided into two groups. The study group (16
      patients) rinsed with benzydamine containing solution, the control group (16
      patients) received placebo solution for rinsing the same way for ten days.
      Differences were found between the two groups favouring the benzydamine
      containing solution. Pain reduction, mouth dryness and diminution of burning
      sensation were detected by means of visual analog scale (VAS). Benzydamine rinses
      could be effective in the management of BMS, but clinicians need to monitor
      patients for possible side effects in the case of long-term use.

PMID- 15853200
TI  - [Use of questionnaires in screening for risk factors in the dental care of
      elderly patients].
AB  - The medical and dental history is one of the crucial part of the routine dental
      practice. According to a survey performed in 2001 27% of the total Hungarian
      population was above the age of 60. The prognosis forecasts an increasing
      tendency in life expectancy and an even higher percentage of elderly population
      in the foreseeable future. Due to the increasing life expectancy the risk for
      complications of common dental treatments is also increasing. More care and
      attention should be paid to anticipate the occurrence of sudden complications
      during dental treatment that might also be a life threatening condition. In 1941
      the American Dental Association drew up a questionnaire based on the risk groups
      established by the American Society of Anaesthesiologists (ASA). In 1993 K.J.M.
      de Jong et al. presented the results of their experience with the clinical
      application of these questionnaires. Based on their studies the Dental Working
      Group of the Health Committee of the European Council recommended the European
      application of this questionnaire. The major objective of our investigation was
      to evaluate how this questionnaire--developed by ASA--can assist the proper
      registration of the medical history in dental practice. Our survey also
      investigated how the risk groups distributed among the subjects. The data of 207
      randomly selected individuals from the patient pool of the Dental Faculty of
      Semmelweis University were processed. The data of risk groups distribution is
      outlined here: ASAI:35,8%, ASAII:24%, ASAIII:17%, ASAIV:23,2%. In the age group
      60+ the following distributions were obtained: ASAI:20,9%, ASAII:13,2%,
      ASAIII:24,2%, and ASAIV:41,7%. The results of this survey also confirmed that the
      occurrence of ASAIII and ASAIV risk scores increased in the age of 60+.
      Consequently the number of patients whose treatment plan should be modified due
      to health risk factors is also increasing. It can be stated that the ASA
      classification is appropriate to inform the dentist about the general physical
      status and health problems of the patients that may influence the dental
      treatment.

PMID- 15853201
TI  - [A case of healed orbito-facial mucormycosis with dental origin].
AB  - A case and the treatment of a 42-year-old male patient with orbito-facial
      mucormycosis are presented by the authors. The most important steps in the
      treatment of this opportunistic infection--with a lethality rate of 30-50 %--are
      as follows: immediate diagnosis, specific antimycotic therapy (Amphotericin-B
      treatment), a series of extensive surgical interventions and adequate control of
      patient's diabetes mellitus.

PMID- 15853202
TI  - [Treatment of young permanent teeth following luxation based on two clinical
      cases].
AB  - Treatment of young permanent teeth following luxation based on two clinical cases
      The most problematic field of pediatric dentistry is the treatment of dental
      trauma. There has been a remarkable increase in the number of dental injuries
      resulting in damaged periodontal tissues at the pediatric dentistry department of
      the University of Debrecen. The aim of the authors' present study was to call
      attention to the most common problems emerging during the treatment of dental
      trauma of young permanent teeth following luxation based on two clinical cases.
      Furthermore, the article offers guidance for the more effective therapy of
      traumatized teeth according the IADT protocols in Hungarian.

PMID- 15853203
TI  - [Pastoral psychology, spiritual counseling in dentistry. Review of the
      literature].
AB  - Although there were drastic changes in the XX-th century, still 70% of the
      Hungarian population believe in God, and 10-15% can be counted as active
      believer. A percentage of 44% of the hospitalised patients indicated a need of
      pastoral counseling during the treatment time. In the field of psychiatry and
      psychotherapy the percentage of the need of religious care (pastoral psychology,
      pastoral counseling) may be even higher. In the field of dentistry the increasing
      number of psychosomatic patients justify the introduction of such religious
      treatment methods into the dental care system as well. In this review authors try
      to collect the main points of this special, religious type of therapy to help
      dental professionals working in the field of psychosomatic dentistry in the
      orientation in this interesting and important field.

PMID- 15853204
TI  - [Molecular-pathological diagnosis of gastric cancer].
AB  - Gastric cancer is one of the most common human cancers and is the second most
      frequent cause of cancer-related death in the world. In the course of multistep
      carcinogenesis of the stomach, various alterations of oncogenes, tumor suppressor
      genes, DNA repair genes, growth factors/receptors, cell cycle regulators and cell
      adhesion molecules are accumulated. These can be biological markers of malignancy
      for molecular-pathological diagnosis. The gene expression profile and scoring
      system, based on microarray analysis, have great potential for differentiating
      the character of gene expression in individual cancers and predicting biological
      behavior and chemosensitivity. Genetic polymorphism is an important determinant
      of the endogenous cause of cancer and can be used as a marker for gastric cancer
      risk that will directly connect with personalized cancer prevention. Genetic
      polymorphisms have been also associated with therapeutic efficacy and toxicity of
      anti-cancer drugs. Serial analysis of gene expression (SAGE) is a powerful
      technique to allow genome-wide analysis of gene expression in a quantitative
      manner. By comparing SAGE libraries of gastric cancer with those of various
      normal tissues, novel genes specifically expressed in gastric cancer can be
      selected. If the gene is not expressed in normal crucial organs, the gene can be
      not only a cancer-biomarker but also a therapeutic target with minimal adverse
      effects. A custom-made array, based on SAGE libraries, is useful to study the
      molecular pathogenesis of gastric cancer and obtain information on biological
      behavior. Combined analyses of gene expression profile and genetic polymorphism
      will enable the characterization of the individual cancer and person, that is
      directly connected with personalized medicine and cancer prevention.

PMID- 15853205
TI  - [Brief review of the neuro oncology for recent three decades in Japan].

PMID- 15853206
TI  - [New development of surgical treatment for malignant brain tumors].
AB  - The most important prognosticator for malignant brain tumor patients is the
      degree of tumor removal. On the other hand, surgical removal should not induce
      aggravation of the patient performance status. In accordance with the result,
      surgical planning for glioma should be carefully considered. However, there is no
      standard guide for preoperative planning to date. However, there is no standard
      guide for preoperative planning to the present. We attempted to divide gliomas
      into 5 stages according to the difficulty of the surgery and analyzed the
      relation between the removal rate and each stage. The results demonstrated that
      the stage is correlated with the removal rate. This staging might contribute to
      standardization of glioma surgery. For surgical planning of tumors around the
      motor area, fiber tractography and magnetoencephalography should be very useful.
      As an intraoperative examination, monitoring of motor evoked potential is
      necessary to resect tumors around the motor area. For resection of tumors around
      the speech area, functional brain mapping under awake surgery is the most
      reliable method. In addition to these techniques for safe surgery, neuro
      navigation and chemical navigation using 5-aminolevulinic acid are used to
      achieve of the maximum removal rate. Finally, development of preoperative
      examinations, microsurgical technique, and intraoperative monitoring enabled us
      to do safer and move sure surgery.

PMID- 15853207
TI  - [Resent advances in chemotherapy for malignant brain tumors].
AB  - Most malignant brain tumors are resistant to the chemotherapeutic agents because
      of the existence of several mechanisms or substances such as the blood-brain
      barrier, genes and proteins. Recently many studies have been started to overcome
      the chemoresistance. Especially recent advances in the field of molecular biology
      have contributed to examination of the chemosensitivities of tumor cells. Trials
      for the individualization of the treatment, so-called Taylor-made therapy, is one
      of these challenges. Loss of chromosome 1 p and 19 q is considered to be closely
      related to chemosensitivity in anaplastic oligodendrogliomas. This is one of the
      breakthroughs in the field of chemotherapy for malignant brain tumors. O6
      methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme which reduces
      the cytocidal effect of nitrosourea. In order to overcome the chemoresistance,
      drugs except nitrosourea or some drugs which reduce the MGMT activity are used
      for tumors expressing MGMT. New technology targeting growth factor receptor such
      as EGFR or VEGFR is also applied to cancer chemotherapy. On the other hand, multi
      institutional cooperative studies have been started to obtain evidence in cancer
      treatment. Phase II study for a small number of patients is not sufficient to
      demonstrate the efficacy of the treatment and to establish the standard therapy.
      Multi-institutional randomized controlled study by JCOG Brain Tumor Study Group
      is the first trial for the treatment of malignant astrocytomas under well
      established quality control and quality assurance systems. It can be a model of
      clinical trials for malignant brain tumors in Japan.

PMID- 15853208
TI  - [Highly quality-controlled radiation therapy].
AB  - Advanced radiation therapy for intracranial disease has focused on set-up
      accuracy for the past 15 years. However, quality control in the prescribed dose
      is actually as important as the tumor set-up in radiation therapy. Because of the
      complexity of the three-dimensional radiation treatment planning system in recent
      years, the highly quality-controlled prescription of the dose has now been
      reappraised as the mainstream to improve the treatment outcome of radiation
      therapy for intracranial disease. The Japanese Committee for Quality Control of
      Radiation Therapy has developed fundamental requirements such as a QC committee
      in each hospital, a medical physicist, dosimetrists (QC members), and an external
      audit.

PMID- 15853209
TI  - [Novel immunotherapeutic approach].
AB  - Malignant astrocytoma is the most common primary brain tumor in adults. The
      median survival time of patients with high-grade malignant astrocytoma is about 1
      year, despite aggressive treatment with surgical resection, radiotherapy, and
      cytotoxic chemotherapy. Novel therapeutic approaches are therefore needed to
      prolong survival. Immunotherapy is one such novel approach that has been
      investigated for application with different types of tumors, including brain
      tumors. The author reviews immunotherapeutic approaches for malignant gliomas and
      the relevance of recent clinical trials and their outcomes. A number of
      potentially targetable antigens have been identified in gliomas. Both tenascin
      and epidermal growth factor receptor (EGFR) have been studied extensively as
      targets for direct immune attack via specific antibodies. As a novel target,
      interleukin 13 receptor alpha 2-chain (IL-13 R alpha 2) has been identified. IL
      13 R alpha 2 is abundantly and specifically overexpressed in glioblastoma
      multiforme, and recently a MHC class I-restricted CTL epitope has been
      identified. Dendritic cells (DCs) are professional antigen presenting cells
      (APCs) that have a unique potency for activating T cells. DCs have been
      investigated in several clinical trials in patients with malignant tumors
      including malignant gliomas. So far, seven papers concerning immunotherapy with
      DCs against malignant gliomas have been published. These reports demonstrate that
      immunotherapy with DCs induces immune responses and clinically antitumor effects
      in some patients with malignant glioma. In addition, none of these studies
      reported evidence of autoimmune neurotoxicity.

PMID- 15853210
TI  - [Gene therapy for brain tumors--present conditions and prospects].
AB  - Malignant brain tumors, particularly malignant gliomas, are one of the most
      difficult diseases to cure. Gene therapy for malignant gliomas has been
      clinically applied since 1992 as an advanced therapeutic strategy for a
      breakthrough. Suicide gene therapy with retroviral or adenoviral vectors was the
      mainstream at first. Now protocols of immune gene therapy and oncolytic therapy
      with replication competent virus only within tumor cells are increasing in
      number. So far, it would be difficult to hold that gene therapy for malignant
      brain tumors has shown a remarkable therapeutic effect. However, gene therapy
      would be a more powerful tool for exploration of therapeutic genes on the basis
      of molecule antitumor mechanisms, improvement of gene expression systems and
      amelioration of gene delivery methods. Besides in addition, cooperation among
      industry, administration and university is necessary for promotion of basic and
      clinical research as well as the development of gene therapy to overcome
      malignant brain tumors.

PMID- 15853211
TI  - [Mangement of brain metastases based on EBM].
AB  - Some three hundred thousand of patients die of cancers yearly and at least 20
      40%, i. e., 60,000-120,000 of them suffered from brain metastases. Those with
      such metastases have a generally poor outcome with a median survival of 1-2
      months with steroids only, and approximately 6 months with whole-brain radiation
      therapy (WBRT). The results of important and historical clinical trials including
      surgery, WBRT, stereotactic radiosurgery (SRS), and chemotherapy are reviewed.
      Surgery with WBRT has been used in the treatment of a single brain metatasis with
      a diameter of more than 3 cm, while survival time of those patients is
      approximately 12 months. SRS including gamma knife is widely used for treatment
      of small and multiple brain metastases. However, many clinical studies have
      revealed that SRS+WBRT is superior to WBRT or SRS alone in survival time and
      local control rates. The accurate incident rates of radiation-induced dementia or
      neurological deficit are still unclear, so the problem and possible avoidance of
      an additional WBRT after surgery or SRS are discussed. To improve neurologic
      function and survival, the treatment for patients with brain metastases should be
      selected with accurate knowledge of EBM.

PMID- 15853212
TI  - [Modified pharmacokinetic modulating chemotherapy for progressive gastric cancer
      accompanied by peritoneal dissemination].
AB  - Peritoneal dissemination is a major event in the development of gastric cancer.
      However, most patients with it have been excluded from clinical studies because
      they rarely have measurable lesions. We conducted an analysis to evaluate the
      efficacy and feasibility of modified pharmacokinetic modulating chemotherapy, for
      gastric cancer patients with peritoneal dissemination. Between May 2002 and April
      2004, 10 patients were treated by modified pharmacokinetic modulating
      chemotherapy. This analysis was based on 10 consecutive chemotherapy-naive
      patients with confirmed peritoneal dissemination. This therapy regimen was
      repeated with a weekly schedule of MTX 100 mg/body, given as intraarterial
      infusion 1 h prior to a 24-hr infusion of 5-FU 500 mg/body. Simultaneously,
      enteric-coated tegafur/uracil (400 mg) was administered every day. The one-year
      overall survival rate was 50. 0%. The median survival time was 311 days. Grade 1
      stomatitis and Grade 1/2 oral dryness were involved in 40% of the cases. No
      patient had to discontinue this therapy because of complications. Objective
      improvement of ascites was seen in all patients, and all patients could be
      treated at outpatient clinics. This regimen may be well-tolerated and of clinical
      benefit for patients with peritoneal dissemination of gastric cancer.

PMID- 15853213
TI  - [A dose escalation study of concurrent chemoradiation therapy with nedaplatin for
      cervical cancer].
AB  - Doses of nedaplatin (CDGP) were established for concurrent chemoradiation therapy
      (CCRT) for cervical cancer, and a collaborative dose escalation study involving 8
      hospitals was conducted to investigate the safety and efficacy of this therapy.
      Radiotherapy was performed according to the standard treatment described in the
      Regulations of Cervical Carcinoma Treatment. CDGP at 80 mg/m2 as Level 1 or at 90
      mg/m2 as Level 2 was administered on Days 1 and 29 of treatment. Dose-limiting
      toxicity (DLT) was observed in 1 of 6.patients receiving 80 mg/m2 of CDGP and in
      all 2 patients receiving 90 mg/m2 of CDGP; therefore, Level 2 was regarded as the
      maximum tolerated dose (MTD), and Level 1 as the recommended dose. DLT signs
      consisted of delayed improvement in the leukocyte count in 2 patients and
      anorexia in 1 patient, suggesting that delayed improvement in the leukocyte count
      is the main DLT of this combination therapy. The main side effects were digestive
      disorders such as nausea and anorexia and bone marrow suppression, such as
      leukopenia, neutropenia, and thrombopenia. Side effects in the Level 1 group were
      more mild than in the Level 2 group. The efficacy was PR or better in all
      patients. The CR rates were 60% (6/10) in the Level 1 group and 50% (1/2) in the
      Level 2 group; there was no marked difference between the two groups. These
      results suggest that CCRT involving administration of CDGP at 80 mg/m2 on Days 1
      and 29 is safe and effective.

PMID- 15853214
TI  - [A clinical study of YM 294 (rhlL-11) in patients with gynecologic cancer].
AB  - YM 294 was administered for chemotherapy-induced thrombocytopenia in patients
      with gynecologic cancer at a dose of 50 microg/kg in order to examine the
      efficacy and safety by a randomized trial, using the non-treatment observation
      group as a control. Increase in the nadir platelet counts as well as shortening
      of the days to return the platelet number to>100,000/ microl were significantly
      higher in the 50 microg/kg groups, in comparison with the non-treatment
      observation group. The major adverse drug reactions observed in the 50 microg/kg
      groups were edema, erythema of injection site, and fever. All of these adverse
      reactions were either mild or moderate (not serious), and they resolved. Abnormal
      changes in laboratory value for which a casual relationship with the study drug
      could not be excluded were reversible and manageable. The efficacy and safety of
      50 microg/kg groups for chemotherapy-induced thrombocytopenia in patients with
      gynecological cancer was confirmed by the results of this study.

PMID- 15853215
TI  - [An early phase II clinical study of YM 294 (rhlL-11) in patients with solid
      tumors and malignant lymphoma].
AB  - An early phase II study was conducted to examine the efficacy and safety of YM
      294 on chemotherapy-induced thrombocytopenia in patients with solid tumors and
      malignant lymphoma. The response rates which were judged as having good or
      excellent efficacy by the investigators were 66.7% in all groups with 25
      microg/kg or more, and the increase in nadir platelet counts and decrease in
      platelet transfusions were observed. Adverse reactions were fever, edema,
      abnormal electrocardiogram and weight gain. All adverse reactions as well as
      abnormal changes in laboratory values for which the casual relationship with the
      study drug could not be excluded were resolved and proved to be not serious. The
      results of this study suggest the efficacy of YM 294 at 25 microg/kg or more for
      chemotherapy-induced thrombocytopenia in patients with solid tumors and malignant
      lymphoma. It was considered that a study should be performed to assess the
      efficacy and safety of YM 294 using a dose of 25 microg/kg or more in the future.

PMID- 15853216
TI  - [Dose response curve of paclitaxel measured by histoculture drug response assay].
AB  - Dose response curves of paclitaxel were measured by histoculture drug response
      assay (HDRA) in 11 lung cancer patients. Inhibition rates of paclitaxel at
      several concentrations were measured and fitted to the sigmoid dose response
      curve, using non-linear least square analysis, with fitting equation y=A (1
      1/(1+exp (b (x-log (ED50)). Parameters A, b, and ED50 were 88.3+/-6.0 (80.0
      100.0) %, 9.57+/-4.32 (2.25-15.0), and 26.8+/-8.1 (15.0-41.0) microg/ml,
      respectively. The parameter b was lower in well-differentiated tumors compared
      with moderately and poorly-differentiated tumors. Dose response curves of
      paclitaxel could be measured by HDRA in lung cancer. This method provides us more
      information for drug sensitivity than the usual HDRA method. This may lead to the
      improved accuracy of HDRA.

PMID- 15853217
TI  - [A case of CA19-9 producing gastric cancer treated by low-dose administration of
      TS-1 for adjuvant chemotherapy].
AB  - A 72-year-old woman underwent total gastrectomy for CA19-9 producing gastric
      cancer. TS-1 was administered for recurrent gastric cancer because the duodenal
      stump was histologically positive and the serum CA19-9 level elevated after
      temporary regression. The dose was reduced from 80 mg/body/day to 50 mg/body/day
      because of grade 3 neutropenia. One course consisted of consecutive
      administration for 28 days followed by 14 days' rest. Upon the completion of the
      second course, the serum CA19-9 level became within normal limits, and no
      recurrence nor remarkable adverse reaction has been recognized for 6 courses.
      Adjuvant use of TS-1 for gastric cancer is ongoing as clinical trials, however,
      the incidence of adverse reaction does not seem to be negligible with
      administration of the recommended dose. Low-dose administration of TS-1 is
      thought to be one effective method of postoperative adjuvant chemotherapy for
      gastric cancer.

PMID- 15853218
TI  - [Three advanced gastric cancer patients successfully treated by combination
      therapy of docetaxel and TS-1].
AB  - We have experienced three gastric carcinoma cases successfully treated by the
      combination therapy of docetaxel and TS-1. Case 1: 66-year-old male with advanced
      gastric cancer invading the pancreas with metastasis to the liver and left neck
      lymph nodes. Case 2: 50-year-old female with scirrhous gastric carcinoma causing
      huge amount of malignant ascites. Case 3: 59-year-old male with recurrent gastric
      cancer of the remnant stomach presenting with obstruction and vessel involvement.
      Primary and metastatic diseases of these patients were remarkably improved with
      the combination therapy, indicating that the combination therapy of docetaxel and
      TS-1 can be a new therapeutic tool for advanced and recurrent gastric cancer
      patients.

PMID- 15853219
TI  - [A patient with multiple bone metastases from gastric cancer after an 8-year
      disease-free interval following gastrectomy].
AB  - We present a patient with multiple bone metastases who was treated successfully
      using only TS-1. Metastasis was diagnosed 8 years after distal gastrectomy for
      early gastric cancer in a woman now 61 years old. Surgery was performed on
      February 13, 1995. The primary tumor was located in the midportion of the gastric
      body, and had invaded the submucosa with metastasis to lymph nodes in the area of
      the lesser curvature and the left gastric artery. She was discharged from our
      hospital 41 days after surgery. After the 8 years of follow-up, elevation of
      alkaline phosphatase (ALP: 1,029 IU/l) was noted. Bone scintigraphy disclosed
      scattered areas of uptake in systemic bones. The biopsy specimen from the pubic
      bone contained metastatic adenocarcinoma, and the bone lesions were diagnosed as
      multiple bone metastases from gastric cancer. Chemotherapy was started with oral
      administration of TS-1 alone at 80 mg/day for 2 weeks, followed by 2 weeks of
      rest. The patient did not experience any side effects, and treatment was repeated
      on an outpatient basis. At 4 month after initiation of therapy, decreases in ALP
      and number of foci of abnormal bone uptake in scintigrams were noted. She has
      survived for an additional 16 months after starting TS-1, without major
      complications.

PMID- 15853220
TI  - [A case of advanced gastric cancer with pulmonary carcinomatous lymphangiosis
      responding remarkably to combination chemotherapy of docetaxel (TXT) and TS-1].
AB  - A 51-old-female patient was admitted because of dyspnea. This case was diagnosed
      inoperable advanced gastric cancer and pulmonary carcinomatous lymphangiosis. She
      was treated by combination of docetaxel (TXT) and TS-1. TXT (40 mg/m2) was
      administered on day 1, and TS-1 (80 mg/body/day) was then administered for 14
      days followed by a 7-day interval as one course. After two courses of
      chemotherapy, carcinomatous lymphangiosis declined, tumor markers decreased, and
      dyspnea improved. Administration of oxygen was thus discontinued. No side effects
      appeared (hematological or non-hematological).

PMID- 15853221
TI  - [A case of advanced gastric cancer with bone metastasis and severe DIC responding
      to hypertensive subselective chemotherapy with pharmacokinetic modulating
      chemotherapy].
AB  - We report a 47-year-old female patient who was suffering from severe DIC due to
      multiple bone metastases. This patient was treated weekly with an intraarterial 5
      FU (500 mg) and MTX (100 mg) including AT-II by a subcutaneously implanted port
      system placed into her abdominal aorta. Furthermore, she was administered
      tegafur/uracil (400 mg/day) 5 days weekly for pharmacokinetic modulating
      chemotherapy (PMC). After three courses of PMC treatment, DIC was resolved and
      the tumor marker was reduced. However, after 22 courses of this regimen, DIC
      suddenly recurred. As second line chemotherapy, we then administered paclitaxel
      (80 mg) in place of CDDP. After five courses of this second line chemotherapy,
      DIC recovered and the tumor marker was again decreased. We concluded that this
      chemotherapy is effective for advanced gastric cancer complicated with bone
      metastasis and DIC from the standpoint of toxicities, antitumor effect and QOL of
      the patient.

PMID- 15853222
TI  - [A case with advanced carcinoma of the gallbladder responding to UFT
      monotherapy].
AB  - Gallbladder carcinoma is a fatal disease with highly metastatic potential, and
      the chemotherapeutic regimen has not been established yet. We reported here a
      case of gallbladder carcinoma with lung and liver meatstases responding to a
      single agent, UFT. A 70-year-old female with advanced carcinoma of the
      gallbladder and bilateral pulmonary metastases were treated with UFT 600 mg/day
      weekday for half a year. Pulmonary metastases disappeared completely, and the
      primary lesion shrank markedly 6 months after. Unfortunately, the patient died
      1.5 years after the start of treatment due to relapse of liver and lung lesions.

PMID- 15853223
TI  - [Three cases of advanced breast cancer successfully treated with a weekly dose of
      paclitaxel].
AB  - We report three cases with advanced breast cancer were treated with a weekly dose
      of paclitaxel (TXL). Case 1: A 52-year-old female, diagnosed as having bilateral
      breast cancer with metastatis to right lung (S9) and sternum. A TXL weekly
      regimen was started (80 mg/m2 with the administration of the drug for three weeks
      followed by one week rest as one course). After twelve courses of treatment,
      bilateral breast masses significantly regressed with the disappearance of
      bilateral axillary and parasternal lymph node metastasis. The tumor marker was
      normalized, too. After two years and four months, the patient is still alive and
      continuing the weekly TXL regimen. Case 2: A 51-year-old female with right breast
      cancer and skin ulcer formation. After completing two courses of weekly TXL
      regimen, her mass was markedly reduced in size, which made it possible for her to
      undergo a modified mastectomy. Case 3: A 52-year-old female with breast cancer
      which invaded the skin. As a result of two courses of weekly TXL therapy, the
      tumor responded significantly and a modified mastectomy was conducted. The TXL
      weekly regimen seems to be very effective in regressing breast tumors and can be
      given safely in the outpatient setting with an extremely high utility profile as
      neoadjuvant chemotherapy as well.

PMID- 15853224
TI  - [A case of recurrent breast cancer with multiple lung, adrenal, inferior vena
      cava tumor thrombus and bone metastases successfully treated with 5'-DFUR and
      hormonal therapy].
AB  - A 42-year-old woman with multiple organ metastases from breast cancer was
      successfully treated with 5'-deoxy-5-fluorouridine (5'-DFUR) and hormonal therapy
      (leuprorelin+tamoxifen). She underwent radical mastectomy for advanced left
      breast cancer in June 1998. In September 2000, she was treated with docetaxel for
      multiple lung metastases, and the lesions were diagnosed as in complete
      remission. In June 2001, she received radiation for bone metastasis in left
      femoral and received a resection of subcutaneous metastases in the face. Then she
      received 2 courses of paclitaxel. In May 2002, she had multiple lung metastases,
      right adrenal metastasis, tumor thrombus in the inferior vena cava and multiple
      bone metastases, and was treated with cycrophosphamide, epirubicin, and 5-FU,
      however, they were abandoned due to severe leucopenia. Therefore, 600 mg/day of
      5'-DFUR was administered from December 2002. The lesions of lung and adrenal
      decreased extendedly in March 2003. She was diagnosed as being in CR in March
      2004, and this condition has continued to the present.

PMID- 15853225
TI  - [A case of recurrent breast cancer with bone metastasis causing pancytopenia-
      efficacy of low-dose CPT-11+ MPA].
AB  - A 46-year-old woman underwent breast-conserving surgery. The patient was treated
      with six cycles of CMF and, subsequently, combination therapy with UFT and CPA.
      However, multiple metastases were detected in the thoracic vertebrae after two
      years and two months of surgery. Weekly administration of paclitaxel was
      initiated, but the drug could not be continued due to pancytopenia. CPT-11 (40
      mg/body) once a week and medroxyprogesterone acetate (MPA) 600 mg a day was
      substituted for paclitaxel. During the treatment with CPT-11, no severe adverse
      reactions, such as myelosuppression and diarrhea, were observed, and the
      patient's condition was stable without discontinuing the chemotherapy. The
      results suggest that the low-dose CPT-11 and MPA therapy should improve the
      prognosis of advanced and recurrent breast cancers with only slight adverse
      effects.

PMID- 15853226
TI  - [Case of gastric perforation after TAI (trancatheter arterial infusion) of SMANCS
      with special reference to accessory left gastric artery].
AB  - In 1993, a 55-year-old-man was diagnosed with chronic active hepatitis (HCV). In
      January 1999, a solitary hepatocellular carcinoma (HCC) was discovered in his
      liver S8, and a sub-segmental hepatectomy was performed. In July 1999, multiple
      recurrences in the liver were noticed, and on August 6, 1999, the first SMANCS
      TAE was performed. After that, PEIT was added, and then on July 18, 2000 and
      November 9, 2000, a second and third SMANCS-TAE were carried out, respectively.
      This time multiple HCCs in the bilateral lobes were discovered, and the 4 th
      SMANCS-TAE was undergone on April 12, 2001. On a celiac angiogram, the right
      hepatic artery was shown to have been obliterated by the last TAE. In addition,
      accessory left gastric artery (accessory LGA) originating in the left hepatic
      artery (LHA) proximal to the umbilical point (UP) could be seen. So we advanced a
      microcatheter to the LHA distal to the accessory LGA and injected SMANCS (0.8 mg)
      into the left hepatic artery. On April 24, he was admitted to hospital by
      ambulance due to severe upper abdominal pain. The muscular defense was noticed,
      and an air pocket under the diaphragm was indicated on an X-ray. An emergency
      total gastrectomy and R-Y re-construction were performed under the diagnosis of
      gastric perforation. A hole of approximately 10 cm in diameter was found in the
      anterior wall between the cardia and the upper body, and the accessory left
      gastric artery (LGA) was obliterated. The principal known side effects of SMANCS
      are fever, nausea and vomiting. However, as far as this writer has investigated,
      gastric perforation has never been reported. SMANCS presumably can flow into the
      stomach wall through the accessory LGA, triggering necrosis of the gastric wall
      due to circulatory damage. Although arterial infusion of SMANCS is an effective
      treatment, it causes considerable vascular damage, so intensive follow-up
      treatment is necessary.

PMID- 15853227
TI  - [A case of pulmonary intravascular lymphoma treated with CHOP chemotherapy plus
      rituximab].
AB  - We report a case of pulmonary intravascular lymphoma of large B cell type in a 72
      year-old woman. She had a one-month history of fever and dry cough before
      admission. Chest X-ray revealed ground glass shadow in both lung fields, and the
      high-resolution CT disclosed centrilobular distribution of ground glass
      opacities. Transbronchial lung biopsy demonstrated large lymphoid cells in the
      capillaries of alveolar septa. The tumor cells showed strong immunohistochemical
      reactivity to CD 20. After combined treatment with CHOP and rituximab, clinical
      symptoms, laboratory and radiological findings were improved. As with diffuse
      large B cell lymphoma, CHOP chemotherapy plus rituximab may prove useful as a
      standard regimen for pulmonary intravascular lymphoma.

PMID- 15853228
TI  - [Sentinel node navigation surgery for colorectal cancer].
AB  - Sentinel nodes (SN) are defined as direct drainage nodes from the primary lesion
      and the initial sites of micrometastasis. We have been trying to detect sentinel
      nodes of colorectal cancer using the dying method. The skip metastasis frequency
      was 15.7% (50 cases) among 318 cases with lymph node metastases. The
      identification of SN was possible in 110 (98.2%) out of 112 cases. Saltation
      lymph node metastasis was accepted by 6 examples, but all cases were identified
      as SN. The diagnostic accuracy of lymph node metastasis by a dying method was
      94.5%. In Dukes A cases, 36 of 37 cases (97.2%) were diagnosed correctly.
      Although there are several remaining issues to be solved, sentinel node
      technologies would be great tools to establish individualized minimally invasive
      surgical management of colorectal cancer.

PMID- 15853229
TI  - [Thyroid carcinoma].
AB  - Among thyroid carcinomas, thyroglobulin is a good tumor marker for differentiated
      carcinoma (papillary carcinoma, follicular carcinoma). In particular, it is
      widely used for monitoring of patients with total or near-total thyroidectomy. On
      the other hand, medullary thyroid caricima has a very sensitive and specific
      tumor marker, calcitonin. In inherited medullary carcinoma (multiple endocrine
      neoplasia type 2), RET protooncogene analysis is the best for detecting early
      medullary thyroid carcinoma.

PMID- 15853230
TI  - [Introduction of novel anti-emetic agent, indisetron hydrochloride, developed
      recently in Japan].
AB  - Recently, an anti-emetic agent, indisetron hydrochloride was developed in Japan.
      In the pre-clinical studies, it showed almost similar affinity to 5-HT3 receptor
      as those developed before. Indisetron reduced 2-methyl-5-serotonin (HT)-induced
      bradycardia. The 5-HT3 antagonistic activity was over 20 times more than that of
      granisetron or ondansetron, indicating the excellent anti-emetic activity against
      anticancer drug induced vomiting. After phase I and II clinical studies, phase
      III studies consisting of a comparative double-blind randomized clinical trial
      (comparing with ondansetron) and open clinical trials, the effectiveness and
      safety profiles of this indisetron were clearly shown. From these studies, it was
      considered that indisetron seemed to be equally or more effective against
      chemotherapy-induced nausea and vomiting compared with existed 5-HT3 receptor
      antagonists.

PMID- 15853231
TI  - A comprehensive model for evaluating telemedicine.
AB  - Increasingly, telecommunications and advanced information technologies are being
      used for a variety of activities: clinical, administrative, and
      education/research. These activities are undertaken with the expectation that
      health care delivery will be improved. To validate this expectation, a number of
      investigations have been undertaken to assess the effectiveness and efficiency of
      the activities. Unfortunately, many of these investigations have either been
      incomplete or have applied inappropriate techniques in the evaluation process.
      This is especially true in the attempts to evaluate the cost effectiveness of
      various telecommunication technologies and service delivery. The model presented
      here provides a systematic framework that can be used in evaluating the
      effectiveness, efficiency, and feasibility of telemedicine. The model delineates
      the different aspects and characteristics of an evaluation across three
      dimensions-focus (cost, quality, access), level (individual, community, society),
      and activities (clinical, administration, education/research). These dimensions
      are interrelated, making comprehensive evaluation difficult.

PMID- 15853232
TI  - Home based E-health applications.
AB  - Home based e-health applications use telecommunication and videoconferencing
      technologies to enable a healthcare provider at the clinical site to conmunicate
      with patients at their home. Such an interaction is called a 'virtual visit'.
      Numerous applications are utilizing commercially available monitoring devices and
      the Internet to enable home based disease management and monitoring. The aim to
      meet older adults' desire to remain independent at home while controlling home
      health care costs has also led to the development of "smart home" technologies. A
      smart home is a residence equipped with technology that enhances safety of
      patients at home and monitors their health conditions. Therefore, the devices and
      sensors chosen to be installed and maintained in the older adults' residences
      need to address functional limitations and social and health care needs. This
      paper provides an overview of home based e-health applications and discusses the
      challenges of implementing and evaluating e-health applications.

PMID- 15853233
TI  - Mr. Young's doctor: how must physicians be prepared for practice?
AB  - What will the practice of medicine be like when people use publicly-available
      performance data to choose their physicians, own their own medical records and
      therefore exercise more control over medical decision making than has ever been
      seen in the past? What do these changes mean for the preparation of physicians?
      The Institute of Medicine has set forth six aims for health care in the United
      States, that it be safe, effective, patient-centered, timely, efficient and
      equitable. Achieving this requires new rules for our work in health care and new
      goals for medical education. The University of Missouri-Columbia School of
      Medicine has identified eight key characteristics of its graduating students and
      residents. We believe these are the qualities required for future physicians to
      deliver the care that their patients need and deserve.

PMID- 15853234
TI  - E-health tools and social workers.
AB  - Social workers have been using telemedicine technologies since the late 1950's.
      The use of telemedicine has been most common in mental health practice.
      Psychotherapy using telephones, interactive video and more recently the Internet
      have gained in popularity with social workers in these settings. However, the use
      of e-health tools in medical social work is limited and worthy of further
      investigation. This paper will report promising projects with medical social
      workers and discuss the potential application of e-health tools for these
      practitioners. The purpose of the paper is to advocate for research measuring
      effectiveness of e-health interventions in social work practice.

PMID- 15853235
TI  - Telework for persons with disabilities in the E.U. and the U.S.A: what can we
      learn from each other?
AB  - Persons with disabilities represent a growing population in both the European
      Union (EU) and the United States (USA). The ability to work is a key component in
      achieving independence and full inclusion in society, and employability is
      increasingly seen as an important outcome variable for studies in health and
      disability. However, persons with disabilities face considerable challenges in
      returning to work due to barriers related to transportation, job changes after
      disability, lack of support services in the workplace, and related barriers.
      Telework, or work from a distance, may help to mitigate these obstacles, while
      expanding the range of work options available for persons with disabilities. The
      EU has made substantial policy progress to support telework, but persons with
      disabilities have had only limited long-term success in telework initiatives due
      to lack of work support services. The USA has generally strong support services
      but lacks telework policy infrastructure. The EU and the USA can benefit from
      collaborative work to enhance their complementary strengths.

PMID- 15853236
TI  - Evidence-based retrieval in E-health.
AB  - In this chapter we address the issue of standards for information retrieval to
      support decision making in e-health. Specifically, we consider the issue of
      evidence-based retrieval in the e-health domains of the consumer, healthcare
      practitioner, healthcare researcher, and genomics researcher. We present the
      results of a preliminary study to assess the current state of evidence-based
      retrieval in e-health. Within this study, we reviewed articles in e-health and
      telemedicine to determine the extent to which authors provide details of the
      information retrieval strategies used, as well as evidence of the effectiveness
      of those strategies. We also examined the extent to which the associated journals
      require authors of reviews to explicitly provide details of information retrieval
      strategies that they used, as well as reporting any evidence for the
      effectiveness of those strategies.

PMID- 15853237
TI  - The impact of genomics on E-health.
AB  - The Human Genome Project (HGP) and e-Health are two fundamental changes that will
      alter the way we approach human health and life. These two scientific and
      societal forces will inevitably impact each other. This paper not only explores
      the ways that the HGP will change health care but also investigates the ways that
      e-Health systems will be influenced by the genomic data. The Electronic Medical
      Record (EMR) is discussed at length, including the probable impact on the
      laboratory, pharmacy, computerized provider order entry (CPOE), and other
      components. Thirteen points of a possible genomic future involving the EMR are
      presented. The genomic impact on other e-Health systems includes those at all
      levels of data: population, disease, patient, tissue and organ banks, cellular
      and for specific genes. The genomic impact on consumer health systems is
      explored, including Internet consumer information resources and the movement for
      direct-to-consumer genetic testing. The paper concludes that technology and
      trends of e-Health will enable the upcoming revolution caused by the health
      implications of the research emanating from the Human Genome Project.

PMID- 15853238
TI  - Privacy enhancing techniques in E-health: an overview.
AB  - This overview highlights the relevance of Privacy Enhancing Techniques (PETs) in
      the context of e-Health. A number of validated privacy protecting techniques is
      briefly presented. The implementation of such PETs could provoke, for a number of
      applications, a shift in paradigm, namely from "Privacy through Security" to
      "Security through Privacy".

PMID- 15853239
TI  - Health captology--application of persuasive technologies to health care.
AB  - Professionals in industries such as advertising and sales have used techniques of
      persuasion to enhance the efficacy of marketing campaigns and sales revenues. In
      contrast, health care has traditionally relied on the persuasive power of facts
      and evidence to encourage healthy behavior. The evidence suggests, however, that
      this current approach is failing. Health care experts and opinion leaders cite
      overwhelming evidence of an epidemic in diseases such as obesity and diabetes,
      despite numerous initiatives to educate the public how to prevent morbidity and
      mortality. Health captology, the application of persuasive technology to health
      care, attempts to leverage proven persuasive techniques to improve clinical
      outcomes.

PMID- 15853240
TI  - Speak-eR: an audible web-based medical record for emergency patients.
AB  - Emergency conditions can inhibit the use of clinical data, even when it has been
      professionally collected and structured. Our aim is to improve the assessment of
      patients' medical histories in emergency situations. Under emergency conditions,
      when it may be impractical for health care providers to interact with a visual
      display of patient data, a "speaking" medical record may be useful. We are
      investigating the use of a voice synthesizer in conjunction with MyAngelWeb, an
      Italian web-based medical record service. Only the textual subset of patient
      medical records was considered and restructured according to the needs imposed by
      voice communication. The quality of the received messages was tested. Some
      quantitative features, including the number of words and time durations, were
      considered together with other subjective features, including intelligibility of
      single words and overall significance of the voice messages. Provided that the
      linguistic architecture of a medical records' text is arranged to minimize the
      number of choices presented to the user, and phrases are kept short with few
      acronyms, health care providers can satisfactorily interact with the service..
      Audible medical record delivery may be considered as an effective enhancement to
      those datasets needed in emergencies.

PMID- 15853241
TI  - MobiHealth: ambulant patient monitoring over next generation public wireless
      networks.
AB  - The wide availability of high bandwidth public wireless networks as well as the
      miniaturisation of medical sensors and network access hardware allows the
      development of advanced ambulant patient monitoring systems. The MobiHealth
      project developed a complete system and service that allows the continuous
      monitoring of vital signals and their transmission to the health care institutes
      in real time using GPRS and UMTS networks. The MobiHealth system is based on the
      concept of a Body Area Network (BAN) allowing high personalization of the
      monitored signals and thus adaptation to different classes of patients. The
      system and service has been trialed in four European countries and for different
      patient cases. First results confirm the usefulness of the system and the
      advantages it offers to patients and medical personnel.

PMID- 15853242
TI  - Service level web monitoring in the field management of emergencies.
AB  - Cardiologic Emergency Project is based on a hospital network in Milan, Italy, in
      order to provide patients with more efficient first aid immediately after the
      occurrence of an Acute Coronary Syndrome. The Project includes ECG transmission
      from running ambulances to the 118 telephone central help desk, and from there to
      the suitable hospital. Since the maximum total transfer time should stay within a
      few tens of minutes, and given that a number of different factors may cause very
      dangerous delays, the effective coordination of several healthcare systems,
      devices and organizations is critical. Monitoring of the activities on each
      component is a must. Cardiologic Emergency Project uses a Web application devoted
      to the monitoring and evaluation of the service levels. Web applications allow
      the quantitative monitoring of the durations of extra-hospital operations.
      Several types of tables and graphics are automatically filled for the best care
      of the patient. For example, given a lengthy total time request by a satisfactory
      full ECG transmission, the system allows analysis of the ECG machine, of the
      cellular phone partial-only coverage along the ambulance pathway, of the transfer
      time in rush hours, etc., to determine which elements in the process can be
      improved to avoid future delays.

PMID- 15853243
TI  - E-health in the Scandinavian countries.
AB  - For more than 10 years the Scandinavian countries have been focusing on utilizing
      information technology to increase efficiency in the delivery of healthcare
      services. Over the last 3 years all three countries have built closed secure IP
      based healthcare networks that cover nearly all aspects of the national
      healthcare sector. The next step is to connect the national networks and
      integrate them into one large Scandinavian healthcare network. This paper
      describes the history of e-health in the Scandinavian Countries, the challenges
      and emerging trends.

PMID- 15853244
TI  - The added value of a process oriented hospital information system supporting the
      integrated patient care.
AB  - This paper will demonstrate the added value of a Process Oriented Hospital
      Information System based on the current trends and changes in the organisation of
      patient care in hospitals. To support the integrated patient care with IT, basic
      functionalities will be described.

PMID- 15853245
TI  - Classifying clinical pathways.
AB  - BACKGROUND: Clinical pathways are commonly developed for homogenous patient
      groups. We were wondering if the traditional patient classification systems could
      be used for classifying clinical pathways. METHODOLOGY: To examine the utility of
      patient classification systems for clinical pathways, a sample of 13 clinical
      pathways was analyzed, involving a total of 412 patients. Three classification
      systems were tested: International Classification of Diseases, Ninth Revision
      (ICD9-CM), Clinical Coding System (CCS) data and All-Patient Redefined Diagnosis
      Related Groups (APR-DRG). RESULTS: Categorization with ICD9-CM and CCS shows
      rather wide variation. However, when restricting for the principal codes, CCS
      classification shows an almost homogeneous relationship with clinical pathways.
      APR-DRG's are already corrected for secondary procedures and are difficult to
      assess. Categorization with the Risk Of Mortality (ROM) is more homogeneous than
      with the Severity Of Illness (SOI). CONCLUSION: Patient groups in clinical
      pathways are rather heterogeneous. When restricting for the principal procedures,
      the strongest relationship seems to exist between clinical pathways and CCS.
      Further research is needed to refine this relationship.

PMID- 15853246
TI  - Introduction of wireless integrated care plans at the bedside.
AB  - For years electronic care plans have been touted as an important tool to provide
      better patient care. Until recently however, most efforts were hampered by design
      gaps in available Electronic Patient Record (EPR) systems and the difficulties
      involved in extending continuous care to the bedside. The growth in wireless LAN
      solutions, and the emerging maturity of EPR systems have finally made practical
      implementations possible. An extensive analysis, development and preparation
      phase followed by a pilot on the department of traumatology in the University
      hospital of Gent has proven the possibilities and validity of multidisciplinary
      electronic care plans as an integral part of the EPR. Wireless consultation,
      observation and charting enables bedside management of patient care. Roll-out on
      5 more departments is planned in the coming year.

PMID- 15853247
TI  - A nation-wide project for the revision of the Belgian nursing minimum dataset:
      from concept to implementation.
AB  - This paper describes the process of revising the Belgian Nursing Minimum Data Set
      (NMDS). The study started in 2000. Implementation is planned from 2006. The
      project is divided in 4 major phases. The first phase (June-October 2002) implied
      the development of the conceptual framework based on literature review and
      secondary data-analysis. The Nursing Interventions Classification (NIC) was
      selected as framework for the revision of the NMDS. The second phase focused on
      the language development (November 2002 - September 2003) with panels of clinical
      experts (N=75) for six care programs. They indicated hospital financing, nurse
      staffing allocation and assessment of the appropriateness of hospitalization as
      priorities of a revised B-NMDS. A draft instrument with 84 variables, using NIC,
      was developed during this period. This leads to an alpha version of a revised
      NMDS. The third phase (October 2003 - December 2004) focused on the data
      collection and validation of the new tool. The new NMDS was tested on 158 nursing
      wards in 66 Belgian hospitals from December 2003 until March 2004. This test
      generated data for some 95.000 inpatient days. The interrater-reliability of the
      revised NMDS is tested. The criterion-related validity of the revised NMDS is
      compared with the actual NMDS. The discriminative power of the revised NMDS is
      tested to select the most relevant items for data collection. This will result in
      a beta version of revised NMDS in December 2004. The records of the revised NMDS
      are linked with the hospital discharge dataset and other mandatory datasets to
      integrate the revised NMDS in the broader health care management. The fourth
      phase (January-December 2005) will focus on information management.

PMID- 15853248
TI  - From patient data to information needs.
AB  - The goal of this paper is to contribute to the improvement of the quality of
      care. For physicians, it is a problem that they are often not aware of gaps in
      their knowledge and the corresponding information needs. Our research aim is to
      resolve this problem by formulating information needs automatically. Based on
      these information needs, patient-specific literature can be retrieved. As a first
      step, we investigate how to model a physician's information needs. Thereafter, we
      design and analyse an approach to instantiate the model with patient data,
      resulting in information-need templates that are able to represent patient
      specific information needs. Our experiments show that a physician's information
      needs can be modelled adequately and can be substantiated into patient-specific
      information needs. Since the number of formulated information needs is rather
      high, future research will focus on methods that restrict the set of
      automatically formulated information needs to a more specialized set.

PMID- 15853249
TI  - Quality of care assessment using GPs' electronic patient records: do we need data
      from home visits?
AB  - The paper tackles the topic of collecting data from home visits using the
      electronic patient record (EPR) of general practitioners (GPs), in a context with
      a high proportion of home visits in primary care. Since data from home visits,
      representing about 40% of GPs' consultations in Belgium, are rather scarcely
      recorded in the EPR, we wanted to study the impact of not taking into account
      home visits for quality assessment in primary care. Five quality indicators,
      which measured the accordance of the delivered care with guidelines on the
      management of osteoarthritis, were compared between a pooled database
      (consultations and home visits) and a restricted database (after removal of home
      visits). Our findings suggest that removing home visits from a database collected
      from primary care may provide a slight modification of the estimate of the
      quality of care, whereas conclusions on quality improvement remain relatively
      stable. Quality of care assessment with the EPR of GPs seems not to be
      dramatically hampered by the poor recording rate of home visits in the EPR.

PMID- 15853250
TI  - Exploitation of electronic medical records data in primary health care.
      Resistances and solutions. Study in eight Walloon health care centres.
AB  - INTRODUCTION: The Electronic Medical Records (EMR), used every day for primary
      health care may constitute an instrument for gathering locally usable data to
      improve the quality of care and, on a larger scale, be a basis of epidemiological
      data. In spite of a policy of promotion of the EMR made by the Federation of
      French-speaking Belgian "Medical Houses", its use remains very marginal. METHODS:
      Eight Medical Houses, motivated by computerization of medical records have been
      met. Quantitative indicators of use of the EMR have been assessed. A qualitative
      assessment of the resistances to computerization, and solutions which can be
      brought, has been realized through the technique of the nominal group. RESULTS:
      The use of the EMR remains slight, allowing for exceptions. The proposed
      solutions could be put together in 5 categories : ethics, training, search for
      sense, practice and interdisciplinarity. DISCUSSION: The practitioners are
      willing to computerize if they get immediate advantages (knowledge of their
      patients and their team operating). They expressed the need of having a tool easy
      to use, that doesn't make them lose time and that has respect for their
      specificity of work and organization (interdisciplinary and self-managed teams).
      They expressed the need of an external support, under the form of adapted
      training and supervision for the data management. Ethical concerns (security,
      data transfer, place of the computer in the relationship with the patient) are
      surprisingly not present enough.

PMID- 15853251
TI  - PropeR and archetypes.
AB  - The PropeR project studies a genric combination of an electronic health record
      (EHR) and decision support software (DSS). This study comprises different medical
      domains. GOAL: Develop a distributed EHR system that is flexible enough to be
      used in different domains without major modifications. METHODS: Use of standards
      and standardized specification and available open source components to develop an
      EHR system that meets the goals. RESULT: PropeRWeb is a generic webbased EHR
      system that is flexible enough to easily accommodate different domains.
      DISCUSSION: Discussion of some of the problems encountered in the development of
      the EHR system.

PMID- 15853252
TI  - Incorporating evaluation into the design of a decision-support system.
AB  - Medical decision support systems will only be accepted by the medical community
      if properly evaluated. However, little attention has been given in the scientific
      literature to the topic of how to incorporate evaluation issues into the design
      of a decision-support system. In this paper, we describe work in developing a
      decision-support system that is intended to support the management (diagnosis and
      treatment selection) of ventilator-associated pneumonia in patients. From the
      beginning of the development of this system, we have taken care to incorporate
      evaluation issues into the design of the system. In the paper, we analyse the
      problems that need be taken into account when evaluating a system. Next, we
      describe the consequences for the functionality of the system.

PMID- 15853253
TI  - Introduction of an operating room information management system improved overall
      operating room efficiency.
AB  - Operating Room (OR) information systems should manage the OR time, assigned to
      every surgeon, thereby minimizing the sum of costs of unused OR time and
      minimizing the costs of elective cases performed outside normal allocated OR time
      (excess OR-time). The aim of this paper is to illustrate how the introduction of
      an OR information system influenced daily OR activity performance. Since January
      2001, we introduced an OR information system with a visual, airport-like, screen
      as central part, displaying all scheduled OR activity linked in real-time
      activity with all OR theatres. For the aim of this paper, we compared all data of
      OR activity for elective abdominal surgery (EAS) for the first half of 2000
      compared to the first half of 2001, after the introduction of our information
      system. In 2000, 764 elective cases were performed, compared to 815 cases in
      2001. For both periods, the total OR time allocated to EAS for this 6 months
      period was 805 h. For 2000, the total duration of OR activity for EAS was 1044 h
      50 min (implicating 239 h 50 min over-time), compared to 1127 h 35 min
      (implicating 322 h 35 min overtime) for 2001. For 2000, we recorded 147 h 20 min
      excess time (=exceeding the time limits of OR activity and inducing extra costs)
      and 46h45min unused OR time. For 2001, we recorded 123 h 04 min excess time and
      35 h 21 min unused time. In conclusion, in 2001 we recorded an increase in total
      OR activity for elective abdominal surgery by 7% in number of procedures and by
      8% in total duration. However, in 2001 we recorded a decrease in excess time by
      16% (123 h 04 min vs 147 h 20 min), which was for a large part due to a 23%
      decrease in unused OR time in 2001 compared to 2000 (35 h 21min vs 46 h 45 min).
      Therefore, the introduction of an OR information system, with a real-time visual
      display of ongoing OR activity, resulted in a increased performance of OR
      activity, with more OR procedures performed despite less excess time and less
      extra costs.

PMID- 15853254
TI  - "The declaration of Innsbruck": some reflections.
AB  - In 2003 a workshop was held in Innsbruck, Austria, on the topic of evaluation of
      ICT applications in Health Care. A result of that workshop was the "Declaration
      of Innsbruck". In the current paper we will further elaborate on this declaration
      and discuss some of the activities that are currently undertaken as supportive
      measures to enable the realization of the vision expressed in the declaration.

PMID- 15853255
TI  - Testing the ISO nursing reference terminology model for mapping.
AB  - PURPOSE: The ISO IS 18104 is intended for helping the nursing profession to
      integrate their terminologies into computer systems and into larger health care
      reference terminologies. One purpose of the standard is to map between different
      terminologies. METHOD: This mapping was tested, using three terminologies that
      are relevant for nursing in the Netherlands. Concepts and terms where selected,
      and their equivalence was determined by experts, and next these were dissected.
      RESULTS: The dissection revealed that several concepts can easily be interchanged
      among the three example terminologies, while others cannot, or only for specific
      purposes. CONCLUSIONS: The ISO IS 18104 fulfills this purpose very well and can
      be considered the gold standard for mapping of nursing terminologies.

PMID- 15853256
TI  - Digital signature and electronic certificates in health care.

PMID- 15853257
TI  - Implementation framework for digital signatures for electronic data interchange
      in healthcare.
AB  - This paper aims to propose an action plan for the deployment of the use of
      digital signatures in Belgian healthcare. This action plan is the result of a
      number of technical, legal and organisational requirements. It starts by
      establishing the functional components that are needed to set up a framework for
      the deployment of digital signatures. The main components should implement an
      infrastructure for: --the creation of digital signatures; --the verification of
      digital signatures; --the certification of signature keys; --the certification of
      attributes; --the handling of revocation. The tasks in the action plan are the
      logical consequence of all the functions that need to be addressed. The objective
      of this report is to list what has to be done and how it can be done in the
      context of healthcare, rather to state who will perform the functions required.

PMID- 15853258
TI  - Recommendations regarding national development of standardized electronic health
      care messages.

PMID- 15853260
TI  - Coordination of medical and hospital information.

PMID- 15853259
TI  - Long term preservation of hospital patients records.

PMID- 15853261
TI  - If ontology is the solution, what is the problem?
AB  - In this paper we show the usefulness of an ontological approach for solving some
      problems arising in medicine. We point out the relevance of terminological
      ontologies for disambiguating polysemous terms, for re-organizing very large
      corpora and detecting possible inconsistencies and for managing a catalog of bio
      medical equipments. We also put in evidence the fundamental role played by
      ontologies when integration and interoperability of heterogeneous knowledge
      sources is needed, in particular in the field of clinical guidelines and evidence
      based medicine.

PMID- 15853262
TI  - Biodynamic ontology: applying BFO in the biomedical domain.
AB  - We propose a modular formal ontology of the biomedical domain with two
      components, one for biological objects, corresponding broadly to anatomy, and one
      for biological processes, corresponding broadly to physiology. The result
      constitutes what might be described as a joint venture between two perspectives-
      of so-called three-dimensionalism and four-dimensionalism--which are normally
      regarded as incompatible. We outline an approach which allows them to be combined
      together, and provide examples of its application in biomedicine.

PMID- 15853263
TI  - Bodily systems and the spatial-functional structure of the human body.
AB  - The human body is a system made of systems. The body is divided into bodily
      systems proper, such as the endocrine and circulatory systems, which are
      subdivided into many sub-systems at a variety of levels, whereby all systems and
      subsystems engage in massive causal interaction with each other and with their
      surrounding environments. Here we offer an explicit definition of bodily system
      and provide a framework for understanding their causal interactions. Medical
      sciences provide at best informal accounts of basic notions such as system,
      process, and function, and while such informality is acceptable in documentation
      created for human beings, it falls short of what is needed for computer
      representations. In our analysis we will accordingly provide the framework for a
      formal definition of bodily system and of associated notions.

PMID- 15853264
TI  - Inflammation ontology design pattern: an exercise in building a core biomedical
      ontology with descriptions and situations.
AB  - Formal ontology has proved to be an extremely useful tool for negotiating
      intended meaning, for building explicit, formal data sheets, and for the
      discovery of novel views on existing data structures. This paper describes an
      example of application of formal ontological methods to the creation of
      biomedical ontologies. Addressed here is the ambiguous notion of inflammation,
      which spans across multiple linguistic meanings, multiple layers of reality, and
      multiple details of granularity. We use UML class diagrams, description logics,
      and the DOLCE foundational ontology, augmented with the Description and Situation
      theory, in order to provide the representational and ontological primitives that
      are necessary for the development of detailed, flexible, and functional
      biomedical ontologies. An ontology design pattern is proposed as a modelling
      template for inflammations.

PMID- 15853265
TI  - Context-based task ontologies for clinical guidelines.
AB  - Evidence-based medicine relies on the execution of clinical practice guidelines
      and protocols. A great deal of effort has been invested in the development of
      tools which can automate the representation and execution of the recommendations
      contained within such guidelines, by creating Computer Interpretable Guideline
      Models (CIGMs). Context-based task ontologies (CTOs), based on standard
      terminology systems like UMLS, form one of the core components of such models. We
      have created DAML+OIL-based CTOs for the tasks referred to in the WHO guideline
      for hypertension management, drawing comparisons also with other, related
      guidelines. The advantages of CTOs include: contextualization of ontologies,
      tailoring of ontologies to specific aspects of the phenomena of interest,
      division of the complex tasks involved in creating ontologies into different
      levels, and provision of a methodology by means of which the task recommendations
      contained within guidelines can be integrated into the clinical practices of a
      health care set-up.

PMID- 15853266
TI  - An ontological framework for the implementation of clinical guidelines in health
      care organizations.
AB  - The paper presents the outlines of an ontology of plans and guidelines, which is
      then used as the basis for a framework for implementing guideline-based systems
      for the management of workflow in health care organizations. The framework has a
      number of special features, above all in that it enables us to represent in
      formal terms assignments of work-items both to individuals and to teams and to
      tailor guideline to specific contexts of application in health care
      organizations. It is designed also to enable implementations to do justice to the
      fact that the processes carried out in health care organizations may deviate in
      different ways from the norms set forth in corresponding guideline definitions.
      This means that implementations built in conformity with the framework will be
      marked by a type of flexibility that might make them more likely to be accepted
      by healthcare professionals than are standard guideline-based management systems.

PMID- 15853267
TI  - Gene ontology application to genomic functional annotation, statistical analysis
      and knowledge mining.
AB  - While a massive amount of biomolecular information is increasingly accumulating
      in different databanks, on the other hand high-throughput technologies are
      generating a great quantity of data that need to be annotated with the genomic
      information available, and interpreted. To this aim, the use of specific
      ontologies can greatly help either in integrating different information stored
      within heterogeneous databanks, or in identifying and clustering sequence data
      sharing common characteristics. In the molecular biology domain, the Gene
      Ontology (GO) is the most developed and widely used ontology. To demonstrate its
      great utility in the annotation and biological interpretation of gene sets
      obtained by means of high-throughput experiments, we implemented the web
      application here described. It enables functional annotations of a given gene set
      on a genomic scale and across different species. Within our application the
      annotations provided by the GO vocabulary allow either to easily bind several
      information from different resources, or to cluster annotated genes according to
      their biological characteristics. Through the GO structure it is also possible to
      represent biological concepts with different specificity levels, from very
      general to very precise concepts. Furthermore, the statistical evaluation of the
      categorizations provided by the GO annotations enables to highlight the most
      significant biological characteristics of a gene set, and therefore to mine
      knowledge from data. Our created tool meets the need to manage a vast quantity of
      biological data with a simple user interface adapt also for users with limited
      informatics knowledge, leading them to evaluate the functional significance of
      experiment's results with graphical views and statistical indexes in a well-known
      web browser user interface.

PMID- 15853268
TI  - Evolving from standard vocabularies to formal ontology for an information system
      dedicated to organ transplantation.
AB  - Semantic heterogeneity is a key issue in the deployment of medical applications.
      In this paper, we examine solutions to address semantic heterogeneity for a
      complex organ transplantation information system. The information system that has
      been developed by the French agency for transplantation (EfG) has to gather
      medical information concerning patients and donors for organ allocation,
      epidemiological studies, and public health decisions. We analyze in this context
      the limits of the traditional approach based on a standard vocabulary and a
      relational database for the transplantation domain. We present its evolution
      towards a system that combines a terminology server and a data warehouse. The
      perspective is now to build a formal ontology that may support semantic
      integration in an advanced transplantation information system. Two open issues in
      formal ontology design are discussed. First, providing definitions of all medical
      concepts is not an obvious task if we want those definitions be meaningful,
      formal, and compatible with other ontologies. Second, propagation of properties
      along relations raises the needs for extending description logics with rules.

PMID- 15853269
TI  - Mistakes in medical ontologies: where do they come from and how can they be
      detected?
AB  - We present the details of a methodology for quality assurance in large medical
      terminologies and describe three algorithms that can help terminology developers
      and users to identify potential mistakes. The methodology is based in part on
      linguistic criteria and in part on logical and ontological principles governing
      sound classifications. We conclude by outlining the results of applying the
      methodology in the form of a taxonomy different types of errors and potential
      errors detected in SNOMED-CT.

PMID- 15853270
TI  - Mixed dentition analysis in a Moroccan population.
AB  - The aims of this study were to produce odontometric data for a Moroccan
      population, to test Tanaka and Johnston and Moyers methods, to derive regression
      equations and elaborate a specific orthodontic prediction table for Moroccan
      children. 50 dental casts of Moroccan students (25 males, 25 females, mean age
      22.6 years sd 1.35) were used to perform measurements of the greatest mesiodistal
      widths of all mandibular and maxillary canines and premolars and mandibular
      incisors with an orthodontic calliper. Significant sexual dimorphism was found in
      tooth sizes (p = .001). The study revealed close relationships between the total
      mesiodistal widths of the mandibular permanent incisors and that of the maxillary
      and mandibular canines and premolars. The correlation coefficients (r) and the
      coefficient of determination (R2) were better sexes combined for the maxilla (r =
      0.60 ; R2 = 0.36 ) and for the mandible (r = 0.61 ; R2= 0.37). The regression
      equations elaborated for males and females were used as a basis for establishing
      an orthodontic prediction table for Moroccan children.

PMID- 15853271
TI  - Maxillary tuberosities size and shape in African Blacks total edentulous.
AB  - The manufacturing of impression standardized trays adapted to Blacks total
      edentulous patients is necessary. This study in complement to previous ones
      quantified maillary tuberosity size and shape in a sample of Ivory Coast
      population a very melting pot example in Africa. Hundred maxillary complete
      edentulous casts issuing from impressions with Schreinemakers trays adjusted or
      not with thermoplastic materials. The two tuberosities for each cast were marked
      and measured. The mesiodistal, vestibulopalatal diameters and the vestibule
      heights measurements were computer-generated. Tubercles were not significantly
      different in the two sectors for the same cast. They were elliptical-shaped with
      the mesiodistal length superior to the vestibulopalatal width and they are higher
      than large. There was no statistical correlation between the data. These findings
      are independent from patients age and sex. Therefore it had been proposed three
      standardized impression trays prototypes adapted to African Blacks posterior
      palatal sector according to tuberosity size and shape. This specificity is
      relevant in prosthodontics since individualization of treatment leads to more
      effective treatment by working within the patient's arch from instead of making
      patients fit a single standard.

PMID- 15853272
TI  - [Prevalence of non carious dental lesions in the department of Dakar].
AB  - Non carious dental lesions are destructions of dental external surfaces
      originating from non bacterial cause in opposition to dental caries. We
      distinguish 5 types of non carious dental lesions: attrition, abrasion,
      abfraction, erosion and demastication. These lesions may be pathological or
      physiological. Data dealing with them are not very numerous in the literature.
      Their study shows a real interest in conservative dentistry because of problems
      both aesthetic and functional they set We carried out an epidemiological trial in
      the department of Dakar with as aim providing data on the prevalence of these
      lesions. Our results have disclosed the following rates of prevalence: 60% of
      attrition, 25,55% of abrasion, 7,22% of abfraction, 5,55% of demastication and
      1,68% of erosion. The results indicate once more the importance of the need for
      clinical evaluation of those dental lesions.

PMID- 15853273
TI  - Dental caries status of primary school children aged 4-16 years in southwest
      Nigeria.
AB  - OBJECTIVE: To assess the dental caries status of primary schoolchildren aged 4-16
      in both urban and rural areas of Lagos State, Southwest Nigeria. DESIGN: Cross
      sectional and descriptive. METHOD: Sample comprised of primary school children (n
      = 1,829) selected from five urban non-fee paying schools and three fee-paying
      schools as well as five rural fee-paying schools. Caries was diagnosed based on
      the WHO caries diagnostic criteria (1997). RESULTS: Caries prevalence was 14.4%
      in the urban area and 5.7% in the rural area (p < 0.01). Children from the fee
      paying schools had a caries prevalence of 21% while those from the non-fee paying
      schools had a caries prevalence of 8.1% (p < 0.01). There was no significant
      difference in dft score among 4-6 year-olds, which was 0.33 and 0.32 in both the
      urban and the rural areas respectively but there was a significant difference in
      dft and DMFT score in the older age groups. Most of the caries were unrestored,
      only 3 (0.16%) had filled teeth. 9.1% required restorative treatment, 2.4% had
      teeth for extraction. CONCLUSION: The prevalence of caries is low in the Nigerian
      population studied. Treatment rate is very low.

PMID- 15853274
TI  - Endodontic flare-ups: comparison of incidence between single and multiple visits
      procedures in patients attending a Nigerian teaching hospital.
AB  - The present study was performed to compare the incidence of endodontic flare ups
      in single with multiple visits treatment procedures, to establish the
      relationship between pre-operative and post obturation pain in patients attending
      for endodontic therapy in a Nigerian teaching Hospital. Patients were randomly
      assigned to either single visit or multiple visits group. Data collected at root
      canal treatment appointment and recall visits (1st, 7th and 30th day post
      obturation) include pulp vitality status, the presence or absence of pre
      operative pain, presence and degree of post obturation pain. Presence of
      endodontic flare-ups (defined as either patient's report of pain not controlled
      with over the counter medication and or increasing swelling). The compiled data
      were analyzed using chi-square where applicable. P level < 0.05 was taken as
      significant. Ten endodontic flare-ups (8.1 %) were recorded in the multiple
      visits group compared to 19 (18,3%) flare-ups for the single visit group, P =
      0.02. For both single and multiple visits procedures, there were statistically
      significant correlations between pre operative and post obturation pain (P =
      0.002 and P = 0.0004 respectively). Teeth with vital pulps reported the lowest
      frequency of post obturation pain (48.8%), while those with non vital pulps were
      found to have the highest frequency oh post obturation pain (50,3%), P = 0.9.
      Although the present study reported higher incidences for post obturation pain
      and flare-ups following the single visit procedures, single visit endodontic
      therapy has been shown to be a safe and effective alternative to multiple visits
      treatment.

PMID- 15853275
TI  - Dental health service utilization by children seen at the University College
      Hospital-an update.
AB  - Asymptomatic hospital visits have been generally accepted as health behaviour
      that should be encouraged, although some factors have been identified as factors
      affecting compliance and attendance. A three years prospective study of the
      pattern of dental clinic attendance of children seen at the University college
      Hospital Ibadan was carried out between January 2001-December 2003. A total of
      875 children comprising of 421 (48.1%) males and 454 (51.89%) females formed
      subjects for the study. Results showed that the modal age of presentation was 6
      10yers. 88.8% of the children had symptomatic visits while 11.2% had asymptomatic
      visits and dental caries and its sequel were the frequently diagnosed symptoms.
      67.8% of the symptomatic cases required extraction of their badly broken down
      teeth due to their late presentations at the clinic. Over 80% of the children
      with asymptomatic visits required only oral prophylaxis. In conclusion, an early
      age at presentation and asymptomatic visits are health behaviours that should be
      encouraged through regular dental health education to parents especially mothers.

PMID- 15853276
TI  - Permanent double teeth and hypodontia in a pair of monozygotic twins: case
      report.
AB  - Double and congenitally missing teeth are known to be commoner in the primary
      dentition than the permanent. The knowledge of this trait in the permanent
      dentition in Africa is still poor. This paper describes the clinical findings in
      a pair of monozygotic Nigerian twins. This illustrates the claims of genetic
      basis of such conditions, which have been reported severally in developed parts
      of the globe but not much among the indigenous Nigerian Negroid population
      especially involving the permanent dentition.

PMID- 15853277
TI  - Expectations of treatment and satisfaction with facial appearance in Nigerian
      orthodontic patients.
AB  - The aim of this study was to investigate correlation between satisfaction with
      facial appearance and expectations of orthodontic treatment. The effects of sex
      and age on these variables were also explored. A sample of 201 patients who
      presented for orthodontic treatment at two referral centers in Nigeria: the
      Orthodontic Unit, University College Hospital, Ibadan and Department of Child
      Dental Health, Lagos University Teaching Hospital, Lagos, completed a
      questionnaire on satisfaction with facial appearance and expectations of
      orthodontic treatment. They consisted of 89 (44.3%) males and 112 (55.7%) females
      with age range of 8 to 40 years (mean age, 13.60 +/- 8.03 SD). Correlation
      between patients' expectations, satisfaction with facial appearance, age and sex
      were examined. A multiple regression analysis was used to estimate the effect of
      the initial facial satisfaction on expectations of orthodontic treatment. No
      significant correlation was found between satisfaction with facial appearance and
      patients' expectations. The correlation was invariant over gender, but age was
      found a significant predictor of expectations of orthodontic treatment for
      patients up to 16 years of age (r = .210; p < 0.05). It was concluded that
      satisfaction with facial appearance is not a significant predictor of Nigerian
      orthodontic patients' expectations of treatment. However, age was found a
      significant predictor of orthodontic patients' expectations of treat-ment for the
      child orthodontic population sub-sample.

PMID- 15853278
TI  - The years ahead: addressing the public policy issues that involve us all.

PMID- 15853279
TI  - Understanding genetics: the relationship of disease and genetic predisposition in
      African-Americans.

PMID- 15853280
TI  - Gender differences in community services knowledge, needs, and use among older
      African-Americans.
AB  - The primary purpose of this study was to compare knowledge of use of and need for
      community services between older (60 years of age and older) African-American men
      and women. A secondary purpose was to determine whether predisposing, enabling,
      and health-status factors could predict knowledge of need for, and use of
      specific community services among African-American women and men, 60 years of age
      and older Data were gleaned from a community-based random telephone survey of
      African-Americans (77 female and 23 male), 60 years of age and older, living in
      northeastern Ohio. Data generated from this study were analyzed using chi-square,
      and independent samples t-test, and multiple regression. Findings from this study
      suggested that women had higher levels of knowledge of use of and need for
      community-specific services than their male counterparts. Another finding from
      this study suggested that none of the identified predisposing, enabling, and
      health-status factors found in this study could plausibly explain knowledge of
      need for, or use of community-specific services.

PMID- 15853281
TI  - Senior nursing students respond to an HIV experiential-teaching method with an
      African-American female.
AB  - This experimental study compared an HIV experiential-teaching method to the
      traditional lecture and discussion method to determine if one method was more
      likely to produce significant indications of senior nursing students' willingness
      and perceived preparedness to provide HIV-patient care to affected clients. The
      sample included 70 (N = 70) baccalaureate senior nursing students from one
      university. In this study, 35 (n = 35) students were randomized into either the
      experimental group or into the control lecture and discussion group (n = 351
      Unlike the traditional lecture and discussion method, the experiential-teaching
      method entitled "To be Touched by AIDS" included an affective component with an
      African-American female who was an HIV-Positive intravenous drug user. Findings
      from this study indicated that the experiential-teaching method was efficacious
      in increasing willingness to provide HIV patient care to affected clients using a
      Wilcoxon (Z = -251 p< 0.05) test as compared to the traditional lecture and
      discussion method of teaching Further findings from this study also suggested
      that there was a weak inverse correlation found using a Spearman Rho.
      Nonetheless, there was a statistically significant relationship between perceived
      preparedness and willingness to provide care to affected HIV clients (r(s) = 
      0.26, p = 0.05) in the experiential-teaching group as compared to the traditional
      lecture and discussion group. It is plausible to assume that in light of these
      statistical findings, nurse educators need to incorporate components of HIV
      experiential-teaching methods in an effort to assist future nurses. These
      experiential-teaching methods, such as situational role-playing and patients
      recollections of lived experiences as HIV-Positive individuals would aid future
      nurses in providing optimal healthcare to all patients, but particularly to those
      who are HIV-Positive.

PMID- 15853282
TI  - A comparison of influences on attitudes towards mental health service use in an
      African-American and White community.
AB  - The purpose of this study was to examine the attitudes toward mental health
      service (MHS) use within a sample of African-American and White adults (N = 739)
      and to identify correlates associated with those expressed attitudes. African
      Americans (n = 132) and Whites (n = 607) were interviewed using the Louisville
      Metropolitan Survey that included the Attitudes Toward Seeking Professional
      Psychological Help Scale. Findings from this study indicated that responses
      regarding seeking mental health services were positively correlated with
      educational attainment and gender In addition, further findings also suggested
      that while race was significantly associated with attitudes toward seeking mental
      health services, it was also associated with prior familiarity with mental health
      services African-Americans reported both less willingness to seek mental health
      services and less familiarity with mental health services. The unexpected finding
      of the association between familiarity and attitudes toward mental health
      services use has value in furthering scientific inquiry. Investigation into the
      role of familiarity with mental health services and the decision-making process
      leading to mental health services use in diverse populations holds potential.

PMID- 15853283
TI  - Prevalence estimates of violence in the dating experiences of college women.
AB  - Young women are vulnerable to experiencing psychological, physical, and sexual
      violence and stalking through dating experiences. This study used a correlational
      design to report prevalence estimates of psychological, physical, and sexual
      violence and stalking that occur within the dating experiences of college women.
      This study also compared prevalence estimates of violence between African
      American and White college women. A convenience sample of 863 (N = 863) women
      between 18 and 25 years of age from a private, historically African-American
      college in the south and a private, historically primarily White college in the
      mid-Atlantic completed the Abuse Assessment Screen, and a background data sheet.
      All participants had the option of completing a narrative note. Data analysis
      consisted of frequencies, and chi2. Almost half of the total sample 48% (n = 412)
      reported the experience of violence and of these, 39% (n = 160) reported more
      than one form of violence. Specific prevalence was as follows: psychological
      violence 22% (n = 190), stalking or harassment 31% (n = 266), physical violence
      12% (n = 99), and all unwanted sexual activity 9% (n = 80). Prevalence estimates
      were consistent for African-American and White college students in all types of
      violence except in reporting threats of physical violence and threats plus actual
      physical violence. Study findings highlight the need for nurses to routinely
      screen and assess all young women for psychological, physical, and sexual
      violence and stalking Surveillance efforts will help identify victims and
      potential victims so that appropriate referrals for treatment and support can be
      made.

PMID- 15853284
TI  - Overcoming: breast cancer and its effect on intimacy in middle aged African
      American women.
AB  - There is a dearth of literature addressing the impact of breast cancer treatments
      on intimacy in African-American women. Much of what is known about living with
      the intimate effects of breast cancer comes from studies composed primarily of
      White women. Grounded theory was used to discover the personal and intimate
      concerns of middle-aged African-American women diagnosed with breast cancer
      African-American interviewers conducted interviews with 15 middle-aged African
      American women. Constant comparative analysis revealed a core process of
      "Overcoming" so they could move on with their lives. Overcoming was influenced by
      their partner standing by them so they could adjust and tell others that they too
      could survive breast cancer. For these African-American women, ability to
      overcome was grounded in their spirituality. This study provides suggestions on
      how to provide culturally appropriate care to middle-aged African-American women
      with breast cancer in relation to their personal and intimate lives.

PMID- 15853285
TI  - Osteoporosis among perimenopausal African-American women: the relationship
      between sources of information and levels of knowledge about osteoporosis.
AB  - The aim of this study is to increase awareness of the occurrence of osteoporosis
      in perimenopausal African-American women. This quantitative study was designed to
      measure African-American women's knowledge of osteoporosis and to determine on
      what sources of information about osteoporosis African-American women rely Aside
      from demographic variables, other data were collected to determine which sources
      of information about osteoporosis African-American women use, whether they know
      that osteoporosis is a preventable disease, and whether there is a relationship
      between sources of information and the level of knowledge about osteoporosis
      among these women. Participants consisted of 45 perimenopausal African-American
      women from 42 to 52 years of age residing in Houston, Texas Data were utilized
      from an ongoing research project. Analysis of the data presented suggests that
      there is an association between specific sources of information and the level of
      knowledge about osteoporosis in this age group of African-American women.

PMID- 15853286
TI  - Project Sugar: a recruitment model for successful African-American participation
      in health research.
AB  - Attempts to increase the number of African-Americans participating in clinical
      trials, regardless of age, have been hampered by a lack of published data
      regarding successful recruitment and retention strategies. Successful strategies
      can be used as a guide for future researchers in the design of studies to recruit
      African-Americans, regardless of age, into clinical as well as qualitative
      studies to promote health among this vulnerable population. The goal of the
      primary study was to recruit 400 families with 2 or more family members affected
      with diabetes, totaling 800 participants. Project Sugar utilized the coordinated
      research principals known as CPR (Community, Plan, Reward) to recruit 615 African
      American families totalling 1,230 people known as the Sea Island people (Gullahs)
      in the first five years of the study. The intention of the study was to identify
      markers for diabetes among these Sea Island natives who tended to be genetically
      homogenous. In so doing, specific strategies were identified as serendipitous
      findings for this study. Nonetheless, these serendipitous findings were thought
      to be so integral to success in the recruitment of African-Americans, mainly
      because of their success among this fairly close-knit, historically isolated, and
      significantly genetically homogenous Sea Islanders (Gullah). In recognizing the
      success of this model, an alternate aim was examined to devise rigorous
      scientific strategies to promote methods for recruitment of African-Americans
      into clinical trials aimed at reducing health disparities among this vulnerable
      population. This projects success can be attributed to the involvement of a local
      citizen advisory committee and rewards in the form of services, benefits, and
      incentives to the community. Findings from this alternative aim, which was
      scientifically built on the CPR model, suggest that when services are provided to
      the community, coupled with the use of local community advisory committees, the
      possibilities of recruiting participants into a clinical trial are significantly
      enhanced and augmented.

PMID- 15853288
TI  - Improving applicant interviewing--using a behavioral-based questioning approach.
AB  - Selecting the correct person for the job is crucial for occupational health nurse
      managers. A successful interview takes time to prepare and implement. A
      structured, well-planned interview using behavioral-based questioning can
      significantly increase the amount of information a manager has available to
      determine how a potential candidate may perform in the intended job.

PMID- 15853287
TI  - Lung cancer in African-Americans.
AB  - Lung cancer is the most preventable cancer death, yet African-Americans continue
      to suffer disproportionately from the disease. Lung cancer kills more African
      Americans than any other cancer and most lung cancers are smoking-related. This
      paper will present an overview of the state of the nursing science on lung
      cancer, as well as pertinent lung cancer statistics risk factors myths and facts,
      health beliefs, and psychosocial factors that influence morbidity, mortality,
      smoking behaviors, and smoking cessation. Strategies for addressing community and
      professional education as well as advocacy for tobacco control, smoking
      prevention, and smoking cessation are addressed.

PMID- 15853289
TI  - Alcohol abuse and ethnicity.

PMID- 15853290
TI  - Research with protected populations--vulnerable participants.
AB  - Workers as study participants are a vulnerable population and additional
      considerations for their protection in research are needed. Issues related to
      invasion of privacy and coercion to participate in research studies must be
      carefully weighed and closely monitored. Worker autonomy must be fostered with
      respect to assuring that informed consent is given, meaning the information
      transferred is understood. Research will add to the body of knowledge and advance
      nursing practice, but one must always remember that risks and benefits must be
      balanced to achieve appropriate end results.

PMID- 15853291
TI  - Interdisciplinary practice, education, and research: the expanding role of the
      occupational health nurse.
AB  - The nurses' roles are changing and expanding along with the changing health care
      system. Occupational health and environmental health nurses are in key positions
      to coordinate and direct interdisciplinary practice, education, and research.
      Occupational and environmental health nurses have a broad knowledge base in which
      they deal with employers, employees, stakeholders in communities, different
      governmental organizations, and families. Interdisciplinary collaboration is a
      way to find possible solutions to meet the needs of the work force, their
      families, communities, and the global community. Nurses must educate the
      different disciplines about their worth in collaborative interdisciplinary
      practice, education, and research. No single discipline can help individuals
      reach their full level of well-being. Interdisciplinary practice, education, and
      research should be encouraged for nurses to provide the best care for individuals
      in need of health care.

PMID- 15853292
TI  - Building the occupational health team: keys to successful interdisciplinary
      collaboration.
AB  - Teamwork among occupational health and safety professionals, management, and
      employees is vital to solving today's complex problems cost-effectively. No
      single discipline can meet all the needs of workers and the workplace. However,
      teamwork can be time-consuming and difficult if attention is not given to the
      role of the team leader, the necessary skills of team members, and the importance
      of a supportive environment. Bringing team members together regularly to foster
      positive relationships and infuse them with the philosophy of strength in
      diversity is essential for teams to be sustained and work to be accomplished. By
      working in tandem, occupational health and safety professionals can become the
      model team in business and industry delivering on their promise of a safe and
      healthy workplace for America's work force.

PMID- 15853293
TI  - Emotional intelligence: recognizing and regulating emotions.
AB  - Occupational health nurses are in the unique position to influence health in the
      work force. To maximize this positive health influence, occupational health
      nurses should develop the skills of emotional intelligence. Emotional
      intelligence includes awareness of self and others and empathy. These behaviors
      are congruent with the mission of nursing because they improve health outcomes.
      Occupational health nurses who are emotionally intelligent have improved
      relationships with others, an important aspect of the nursing role. Emotional
      intelligence can be developed. The process begins with self-awareness, enhanced
      through self-care behaviors, such as exercise and journaling. Reading popular
      self-help literature also can improve self-awareness. After a nurse becomes self
      aware, the next phase is to develop an awareness of others. This can be learned
      using the same type of techniques in the self-awareness stage. The final step is
      the development of empathy. This is the active step using the knowledge developed
      in the prior two stages. Through discipline and effort, an individual can learn
      to actively listen to others. This type of listening fosters empathy. By working
      in a positive, caring environment, personal growth in emotional intelligence can
      be enhanced (McMullen, 2003). Through the development of emotional intelligence,
      the nurse can improve personally and professionally, a win-win situation for all
      involved.

PMID- 15853294
TI  - Shaping effective communication skills and therapeutic relationships at work: the
      foundation of collaboration.
AB  - Effective communication is essential to practice and can result in improved
      interpersonal relationships at the workplace. Effective communication is shaped
      by basic techniques such as open-ended questions, listening, empathy, and
      assertiveness. However, the relationship between effective communication and
      successful interpersonal relationships is affected by intervening variables. The
      variables of gender, generation, context, collegiality, cooperation, self
      disclosure, and reciprocity can impede or enhance the outcome of quality
      communication. It is essential for occupational health nurses to qualitatively
      assess the degree to which each of these concepts affects communication and, in
      turn, relationships at work.

PMID- 15853295
TI  - C-reactive protein--should it be used to assess cardiac risk?

PMID- 15853296
TI  - Tuning the enantioselective N-acetylation of racemic amines: a spectacular salt
      effect.
AB  - We have described a spectacular salt effect in the kinetic resolution of (+/-)-1
      phenylethylamine, which leads to an increase in reactivity, high levels of
      selectivity, and a complete reversal of the stereoselectivity. By tuning the
      reaction conditions, we were able to increase the selectivity factor of (1S,2S)-1
      to s = 115.

PMID- 15853297
TI  - Site-specific binding of quinones to proteins through thiol addition and addition
      elimination reactions.
AB  - Ubiquinone-0, menaquinone-0, and 2,3,5-trimethyl-1,4-benzoquinone were site
      specifically bound to free cysteine of proteins (yeast iso-1 cytochrome c as a
      model protein) through thioether bond formation. Model thioether quinone
      conjugates showed unexpected reactivity to cysteine of proteins as their parent
      quinones by thiol addition-elimination reaction. Cyclic voltammetry studies of
      the model compounds showed only minor differences in their redox potentials as
      compared to their parent quinones. Thioether ligation provides a general, simple,
      and fast method to construct model quinone protein systems. In addition, these
      studies also contribute to the understanding of biological activities, toxicity,
      and anti-cancer mechanism of quinones and thioether quinone adducts.

PMID- 15853298
TI  - Polypeptide and carbohydrate structure of an intact glycoprotein from Raman
      optical activity.
AB  - A vibrational Raman optical activity (ROA) study of bovine alpha1-acid
      glycoprotein (AGP) is reported. Using the recently introduced ChiralRAMAN
      instrument from BioTools, Inc., a high-quality ROA spectrum of AGP, measured as a
      small circularly polarized component in the scattered light, was obtained in the
      range of 200-1800 cm-1. Comparison with the ROA spectra of beta-lactoglobulin and
      N,N'-diacetylchitobiose reveals features consistent with previous suggestions
      that the peptide component of AGP has a structure based on the lipocalin fold,
      and that the first two glycosidic links after the N-links to asparagine in the
      pentasaccharide core are of the beta(1-4)-type. A detailed analysis of the band
      patterns may ultimately provide information on the more conformationally
      heterogeneous and functionally crucial peripheral oligosaccharide segments.
      Hence, information about both the polypeptide and carbohydrate components may be
      obtained from the ROA spectra of intact glycoproteins.

PMID- 15853299
TI  - Sorption-desorption behavior of bispyrazolato-copper(II) 1D coordination
      polymers.
AB  - A new polycrystalline vapochromic polymorph of the one-dimensional copper
      bispyrazolate polymer reversibly and selectively absorbs a number of small
      molecules; the crystal structures of the anhydrous and fully hydrated species,
      determined by powder diffraction methods, are markedly different despite their
      simple, fast, and reversible interconversion.

PMID- 15853300
TI  - Electrodeposition of noble metal nanoparticles on carbon nanotubes.
AB  - Noble metal nanoparticles can be electrodeposited on carbon nanotubes under
      potential control. The nanotube sidewalls serve both as the electrodeposition
      template and as the wire electrically connecting the deposited nanoparticles.

PMID- 15853301
TI  - Enzymatic approach to unnatural glycosides with diverse aglycon scaffolds using
      glycosyltransferase VinC.
AB  - Glycosyltransferase VinC was explored for a construction of glycoside libraries
      using dTDP-vicenisamine and structurally unrelated unnatural aglycons, and new
      unnatural vicenisaminides were successfully constructed. Structural elements of
      aglycon recognition by VinC were proposed by modeling studies and were confirmed
      by the success of transglycosylation upon a designed aglycon.

PMID- 15853302
TI  - Protonation of the acidic residues in the transmembrane cation-binding sites of
      the ca(2+) pump.
AB  - The ionization states of the acidic residues around the Ca2+-binding sites of
      sarcoplasmic reticulum Ca2+ ATPase are studied by continuum electrostatic
      calculations and all-atom molecular dynamics simulations with explicit solvent
      and phospholipids. The two methods consistently indicate that Glu58 and Glu908
      are protonated at neutral pH. The Ca2+ coordination and the H-bonds formed by the
      protonation of Glu58 and Glu908 are stable in an MD simulation, whereas the H
      bonds are disrupted and the Ca2+ coordination geometry is severely altered in
      another simulation treating these residues unprotonated. The results clearly
      indicate that the H-bonds formed by protonation of Glu58 and Glu908 provide extra
      stability for the Ca2+-binding sites of Ca2+ ATPase.

PMID- 15853303
TI  - A new family of small molecules to probe the reactivation of mutant p53.
AB  - Cells that express mutant p53 derived from cancers are selectively killed by a
      new class of small organic molecules. The protein p53 is recognized as one of the
      most important guardians in the body that prevents tumor development. Mutant
      forms of p53 are present in approximately 50% of all human cancers. Molecules
      that selectively kill cells expressing mutant p53 could become important
      chemotherapeutic agents. Our research focuses on developing a synthetically
      accessible class of molecules that can be easily modified to examine structural
      activity relationships and mechanism of biological activity or to optimize for
      anticancer activity. In this communication, a new class of molecules that
      selectively arrests growth of cells expressing two forms of mutant p53 is
      described. Synthetic routes to these compounds are also presented.

PMID- 15853304
TI  - Heteronuclear two-bond correlation: suppressing heteronuclear three-bond or
      higher NMR correlations while enhancing two-bond correlations even for vanishing
      2J(CH).
AB  - A novel two-dimensional NMR pulse sequence, H2BC, for long-range correlation of
      1H and 13C nuclei is presented. The experiment has several attractive features
      compared to the widely used HMBC experiment, for example, (a) typically strong
      enhancement of correlations over two bonds while suppressing those over more
      bonds, that is, resolving ambiguities in standard HMBC spectra and showing two
      bond correlations not present in HMBC spectra, (b) independence of long-range 1H
      13C coupling constants, (c) full homo- and heteronuclear decoupling in the
      indirect dimension and heteronuclear decoupling in the acquisition dimension, (d)
      pure 2D absorption peak shapes, and (e) a pulse sequence duration significantly
      shorter than that of HMBC. The experiment is quite complementary to HMBC and does
      not effect correlations to quaternary carbons that must be obtained by HMBC.

PMID- 15853305
TI  - Heterometallic bismuth-transition metal homoleptic beta-diketonates.
AB  - Bismuth(III) hexafluoroacetylacetonate reacts readily with the first row
      transition-metal species to produce trinuclear heterobimetallic coordination
      complexes Bi2M(beta-diketonate)8 (M = Mn, Fe, Co, Ni, Cu, Zn). This unique,
      general approach may offer new possibilities for developing single-source
      molecular precursors for advance oxide materials.

PMID- 15853306
TI  - Reversible insulin self-assembly under carbohydrate control.
AB  - Insulin with built-in pairs of boronates and polyols can produce soluble high
      molecular weight self-assemblies under control by carbohydrates. The illustrated
      principle has potential utility for general protein and peptide protraction and
      controlled drug release.

PMID- 15853307
TI  - Promiscuous catalysis by the tetrahymena group I ribozyme.
AB  - Catalytic promiscuity, the ability of an enzyme to catalyze alternative
      reactions, has been suggested to have played an important role in the evolution
      of new catalytic activities in protein enzymes. Similarly, promiscuous activities
      may have been advantageous in an earlier RNA world. The Tetrahymena Group I
      ribozyme naturally catalyzes the site-specific guanosine attack on an anionic
      phosphate diester and has been shown to also catalyze aminoacyl transfer to
      water, albeit with a small rate acceleration (<10-fold). This inefficient
      catalysis could be due to the differences in charge and/or geometry requirements
      for the two reactions. Herein, we describe a new promiscuous activity of this
      ribozyme, the site-specific guanosine attack on a neutral phosphonate diester.
      This alternative substrate lacks the negative charge at the reaction center but,
      in contrast to the aminoacyl substrate, can undergo nucleophilic attack with the
      same geometry as the natural substrate. Our results show that the neutral
      phosphonate reaction is catalyzed about 1 x 106-fold, substantially better than
      the acyl transfer but far below the normal anionic substrate. We conclude that
      both charge and geometry are important factors for catalysis of the normal
      reaction and that promiscuous catalytic activities of ribozymes could have been
      created or enhanced by reorienting and swapping RNA domains.

PMID- 15853308
TI  - Cooperative Friedel-Crafts catalysis in heterobimetallic regime: alkylation of
      aromatics by pi-activated alcohols.
AB  - The highly active Friedel-Crafts alkylation (FCA) catalyst,
      [Ir(COD)Cl(SnCl3)(SnCl4)(arene)]+Cl- (1-SnCl4), is easily generated in one-pot
      from [Ir(COD)Cl]2 or [Ir(COD)(mu-Cl)Cl(SnCl3)]2 (1) and SnCl4. The reaction of
      arenes, heteroarenes with benzyl, and allyl alcohols is promoted by 1-SnCl4 (1
      mol %) with high turnover frequency. Kinetic evidence is presented to establish
      FCA pattern. From dual-catalyst combination studies varying the transition metal
      and main group metal partner, the efficiency of the present catalysts is
      attributed to the electrophilic "IrIII-SnIV" core.

PMID- 15853309
TI  - Direct evidence for the gas phase thermal polymerization of styrene.
      Determination of the initiation mechanism and structures of the early oligomers
      by ion mobility.
AB  - We present here direct evidence for the thermal self-initiated polymerization of
      styrene in the gas phase and establish that the initiation process proceeds via
      essentially the same mechanism (the Mayo mechanism) as in condensed phase
      polymerization. Furthermore, we provide structural identifications of the dimers
      and trimers formed in the gas phase.

PMID- 15853310
TI  - A magnetic route to measure the average oxidation state of mixed-valent manganese
      in manganese oxide octahedral molecular sieves (OMS).
AB  - A magnetic route has been applied for measurement of the average oxidation state
      (AOS) of mixed-valent manganese in manganese oxide octahedral molecular sieves
      (OMS). The method gives AOS measurement results in good agreement with titration
      methods. A maximum analysis deviation error of +/-7% is obtained from 10 sample
      measurements. The magnetic method is able to (1) confirm the presence of mixed
      valent manganese and (2) evaluate AOS and the spin states of d electrons of both
      single oxidation state and mixed-valent state Mn in manganese oxides. In
      addition, the magnetic method may be extended to (1) determine AOS of Mn in
      manganese oxide OMS with dopant "diamagnetic" ions, such as reducible V5+ (3d0)
      ions, which is inappropriate for the titration method due to interference of
      redox reactions between these dopant ions and titration reagents, such as KMnO4,
      (2) evaluate the dopant "paramagnetic" ions that are present as clusters or in
      the OMS framework, and (3) determine AOS of other mixed-valent/single oxidation
      state ion systems, such as Mo3+(3d3)-Mo4+(3d2) systems and Fe3+ in FeCl3.

PMID- 15853311
TI  - One-bond C-C coupling constants in ethers are not primarily determined by N-sigma
      delocalization.
AB  - One-bond carbon-carbon coupling constants, 1JCC, were measured for a series of
      cyclic and acyclic ethers. Surprisingly, the dependence on COCC dihedral angle,
      tau, parallels cos(tau), rather than the cos(2tau) characteristic of n-sigma*
      delocalization. These results complement recently calculated 1JCH values in three
      ethers. The variations in 1J are not primarily determined by delocalization but
      instead are attributed to a dipolar interaction that affects electron density,
      perhaps via the hybridization.

PMID- 15853312
TI  - Three-component coupling reactions of silylglyoxylates, alkynes, and aldehydes: a
      chemoselective one-step glycolate aldol construction.
AB  - A single-pot three-component coupling reaction of silylglyoxylates (1), terminal
      alkynes, and aldehydes in the presence of ZnI2 and Et3N is presented. The
      products of the reaction, densely functionalized silyl-protected glycolate aldols
      (2), can be converted to the corresponding acetonides (3) in a one-pot
      deprotection/ketalization sequence. A variety of terminal alkynes and aldehydes
      can be successfully employed to give a range of highly functionalized, fully
      protected 1,2-diols in good yields and moderate diastereoselectivities.
      Mechanistic experiments suggest that the zinc acetylide reacts with the
      silylgyloxylate (1) in a chemoselective manner. Using an unoptimized (+)-N
      methylephedrine and Zn(OTf)2 system, silyl-deprotected adduct 2 was formed in 64%
      ee and 89:11 dr.

PMID- 15853313
TI  - CpRu(PN) complex-catalyzed isomerization of allylic alcohols and its application
      to the asymmetric synthesis of muscone.
AB  - Highly efficient isomerization of allylic alcohols into saturated carbonyls is
      accomplished using the catalyst system of Cp*RuCl[Ph2P(CH2)2NH2-kappa2-P,N]-KOt
      Bu (Cp* = eta5-C5(CH3)5) under mild conditions. Mechanistic consideration based
      on isotope-labeling experiments indicated the present reaction is applicable to
      the asymmetric isomerization of racemic sec-allylic alcohols with a prochiral
      olefin via dynamic kinetic resolution. A concise asymmetric synthesis of muscone
      has been achieved, where the asymmetric isomerization using an optically active
      ligand is a key reaction.

PMID- 15853314
TI  - Enantioselective reductive cyclization of 1,6-enynes via rhodium-catalyzed
      asymmetric hydrogenation: C-C bond formation precedes hydrogen activation.
AB  - Asymmetric hydrogenation of 1,6-enynes using chirally modified cationic rhodium
      precatalysts enables enantioselective reductive cyclization to afford alkylidene
      substituted carbocycles and heterocycles in a completely atom economical fashion.
      Good to excellent yields and exceptional levels of asymmetric induction are
      observed across a structurally diverse set of substrates. Mechanistic studies
      involving hydrogen-deuterium crossover experiments, along with the observance of
      nonconjugated cycloisomerization products 14c and 15c, suggest rhodium(III)
      metallocyclopentene formation occurs in advance of hydrogen activation. This
      oxidative coupling-hydrogenolytic cleavage motif should play a key role in the
      design of related hydrogen-mediated couplings.

PMID- 15853315
TI  - Catalytic asymmetric synthesis of esters from ketenes.
AB  - By building on elementary principles of Bronsted acid-base chemistry, a
      nucleophile-catalyzed method for the asymmetric synthesis of esters from ketenes
      has been transformed into a much more versatile and effective Bronsted acid
      catalyzed process. The product aryl esters can be converted into useful
      derivatives, such as enantioenriched alcohols and carboxylic acids.

PMID- 15853316
TI  - Intramolecular [4 + 2] cycloadditions of 1,3-enynes or arylalkynes with alkenes
      with highly reactive cationic phosphine Au(I) complexes.
AB  - New Au(I) complexes with bulky, biphenyl phosphines are the most reactive
      catalysts for the cyclizations of enynes. 1,6-Enynes with an aryl ring at the
      alkyne give 2,3,9,9a-tetrahydro-1H-cyclopenta[b]naphthalenes by a 5-exo-dig
      cyclization followed by a Nazarov-type ring expansion. 1,8-Dien-3-ynes also
      cyclize by a 5-exo-dig pathway to form hydrindanes.

PMID- 15853317
TI  - Single crystal SnO2 zigzag nanobelts.
AB  - Zigzag SnO2 nanobelts have been synthesized by evaporating tin grain in air. XRD,
      SEM, and TEM were employed to characterize the prepared samples. SEM images
      showed large amounts of zigzag nanobelts with periodic morphology. XRD result
      showed a pure tetragonal SnO2 phase. HRTEM and SAED revealed a single crystal
      structure with [010] zone axis on the whole zigzag zone. The zigzag structure is
      deduced to be formed by shifting the growth direction from [101] to [10] or vice
      versa. Growing nanobelts along different equivalent directions opens a new avenue
      for the preparation of novel nanostructured materials.

PMID- 15853318
TI  - PdCl2-catalyzed two-component cross-coupling cyclization of 2,3-allenoic acids
      with 2,3-allenols. An efficient synthesis of 4-(1',3'-dien-2'-yl)-2(5H)-furanone
      derivatives.
AB  - Cross-coupling cyclization reaction between 2,3-allenoic acids 1 and 2,3-allenols
      2, in which two allenes functioned differently, was realized to afford 4-(1',3'
      dien-2'-yl)-2(5H)-furanone derivatives 3. The reaction may proceed via an
      oxypalladation, insertion, and beta-hydroxide elimination process. A high E
      stereoselectivity of the new formed C=C double bond was observed.

PMID- 15853319
TI  - Sodium dialkyl-amidozincates: alkyl or amido bases? An experimental and
      theoretical case study.
AB  - Alkali metal zincate reagents are attracting considerable attention at present in
      respect to their often special reactivity/selectivity in hydrogen-metal and
      halogen-metal interconversion reactions. Heteroleptic diorgano-amidozincates,
      typified by lithium di-tert-butyltetramethylpiperidinozincate, have proved to be
      especially useful reagents in such applications. In this paper the related sodium
      TMP-zincate, prepared as its TMEDA (N,N,N',N'-tetramethylethylenediamine) adduct,
      [TMEDA.Na(mu-tBu)(mu-TMP)Zn(tBu)], 1, is introduced. This new zincate was
      synthesized from a 1:1:1 mixture of tBu2Zn, NaTMP, and TMEDA in hexane solution,
      as a colorless crystalline solid in an isolated yield of 58%. It has been
      characterized in solution by 1H and 13C NMR spectroscopic studies. An X-ray
      crystallographic study reveals that 1 adopts a five-membered (NaNZnCC) ring
      system featuring a TMP bridge and an unusual, asymmetrical tBu bridge involving a
      Na...Me agostic contact. Probing the basicity of 1, reaction with benzene affords
      the new hetero(tri)leptic zincate [TMEDA.Na(mu-Ph)(mu-TMP)Zn(tBu)], 2, which has
      also been crystallographically characterized. Thus, in this hydrogen-metal
      exchange reaction 1 functions as an alkyl base, with the elimination of butane,
      as opposed to an amido base. Also reported are DFT calculations using B3LYP
      functionals and the 6-311G** basis set on model zincate systems, which intimate
      that the preference of 1 for tBu ligand transfer over TMP ligand transfer in the
      reaction toward benzene is due to favorable thermodynamic factors.

PMID- 15853320
TI  - Total synthesis of (+)-13-deoxytedanolide.
AB  - A total synthesis of 13-deoxytedanolide is described. The synthesis features a
      highly stereoselective fragment assembly aldol reaction of methyl ketone 4 and
      aldehyde 5 to establish the complete carbon skeleton of the natural product in
      the form of aldol 15. The facile formation of the remarkably unreactive hemiketal
      16 thwarted attempts to elaborate 15 to tedanolide. However, deoxygenation of the
      C(13)-hydroxyl of 16 provided the 13-deoxy hemiketal 17 that was smoothly
      elaborated to 13-deoxytedanolide.

PMID- 15853321
TI  - Phase- and size-controlled synthesis of hexagonal and cubic CoO nanocrystals.
AB  - Highly crystalline, phase- and size-controlled CoO nanocrystals of hexagonal and
      cubic phases have been prepared by thermal decomposition of Co(acac)3 in
      oleylamine under an inert atmosphere. Kinetic and thermodynamic control for the
      precursor formation leads to two different seeds of hexagonal and cubic phases at
      higher temperatures. The crystal size of both CoO phases can be easily
      manipulated by changing the precursor concentration and reaction temperature.

PMID- 15853322
TI  - Mechanism and origin of enantioselectivity in the Rh2(OAc)(DPTI)3-catalyzed
      cyclopropenation of alkynes.
AB  - The mechanism of cyclopropenations of alkynes with ethyl diazoacetate catalyzed
      by Rh2(OAc)4 and Rh2(OAc)(DPTI)3 (1) is studied by a combination of kinetic
      isotope effects and theoretical calculations. With each catalyst, a significant
      normal 13C KIE was observed for the terminal acetylenic carbon, while a very
      small 13C KIE was observed at the internal acetylenic carbon. These isotope
      effects are predicted well from canonical variational transition structures for
      cyclopropenations with intact tetrabridged rhodium carbenoids. A viable mechanism
      based on the recently proposed importance of a [2 + 2] cycloaddition on a
      tribridged rhodium carbenoid could not be identified. An explanation for the
      enantioselectivity with DPTI ligands is described.

PMID- 15853323
TI  - Thermodynamic evidence for Ca2+-mediated self-aggregation of Lewis X gold
      glyconanoparticles. A model for cell adhesion via carbohydrate-carbohydrate
      interaction.
AB  - Thermodynamic evidence for the selective Ca(2+)-mediated self-aggregation via
      carbohydrate-carbohydrate interactions of gold glyconanoparticles functionalized
      with the disaccharides lactose (lacto-Au) and maltose (malto-Au), or the
      biologically relevant trisaccharide Lewis X (Le(X)-Au), was obtained by
      isothermal titration calorimetry. The aggregation process was also directly
      visualized by atomic force microscopy. It was shown in the case of the
      trisaccharide Lewis X that the Ca(2+)-mediated aggregation is a slow process that
      takes place with a decrease in enthalpy of 160 +/- 30 kcal mol(-)(1), while the
      heat evolved in the case of lactose and maltose glyconanoparticles was very low
      and thermal equilibrium was quickly achieved. Measurements in the presence of
      Mg(2+) and Na(+) cations confirm the selectivity for Ca(2+) of Le(X)-Au
      glyconanoparticles. The relevance of this result to cell-cell adhesion process
      mediated by carbohydrate-carbohydrate interactions is discussed.

PMID- 15853324
TI  - Development of a tandem protein trans-splicing system based on native and
      engineered split inteins.
AB  - Protein trans-splicing involving naturally or artificially split inteins results
      in two polypeptides being linked together by a peptide bond. While this
      phenomenon has found a variety of applications in chemical biology and
      biotechnology, precious little is known about the molecular recognition events
      governing the initial fragment association step. In this study, fluorescence
      approaches have been used to measure the dissociation constant for the Ssp DnaE
      split intein interaction and to determine the on and off rates of fragment
      association. The DnaE fragments bind with low nanomolar affinity, and our data
      suggest that electrostatics make an important contribution to the very rapid
      association of the fragments at physiological pH. This information was used to
      develop a tandem trans-splicing system based on native and engineered split
      inteins. This novel system allows the one-pot assembly of three polypeptides
      under native conditions and can be performed in crude cell lysates. The
      technology should provide a convenient approach to the segmental isotopic or
      fluorogenic labeling of specific domains within the context of large multidomain
      proteins.

PMID- 15853325
TI  - Polypeptide chains containing D-gamma-hydroxyvaline.
AB  - Life has an unexplained and distinct l-homochirality. Proteins typically
      incorporate only l-amino acids into their sequences. In the present study, d-Val
      and d-gamma-hydroxyvaline (d-Hyv; V) have been found within ribosomally expressed
      polypeptide chains. Four conopeptides were initially isolated, gld-V/gld-V'from
      the venom of Conus gladiator and mus-V/mus-V' from the venom of Conus mus. Their
      complete sequences (gld-V/gld-V' = Ala-Hyp-Ala-Asn-Ser-d-Hyv-Trp-Ser and mus
      V/mus-V' = Ser-Hyp-Ala-Asn-Ser-d-Hyv-Trp-Ser) were determined by a combination of
      nano/pico-NMR and MS/MS methods. The amino acid triad that contains the gamma
      hydroxylated residue, Ser-d-Hyv-Trp, is a novel structural motif that is
      stabilized by specific interactions between the d-amino acid and its neighboring
      l-counterparts. These interactions inhibit lactonization, a peptide backbone
      scission process that would normally be initiated by gamma-hydroxylated residues.
      Conopeptides possessing the Ser-d-Hyv-Trp motif have been termed gamma
      hydroxyconophans. We have also isolated analogous conopeptides (gld-V and mus-V)
      containing d-Val instead of d-Hyv; these are termed conophans. gamma
      Hydroxyconophans and conophans are particularly atypical because (i) they are not
      constrained as most conopeptides, (ii) they are extremely short in length, (iii)
      they have a high content of hydroxylated residues, and (iv) their sequences have
      no close match with other peptides in sequence databases. Their modifications
      appear to be part of a novel hyperhydroxylation mechanism found within the venom
      of cone snails that enhances neuronal targeting. The finding of d-Val and d-Hyv
      within this family of peptides suggests the existence of a corresponding d
      stereospecific enzyme capable of d-Val oxidation.

PMID- 15853326
TI  - Reactions of nitrogen oxides with heme models. Spectral and kinetic study of
      nitric oxide reactions with solid and solute Fe(III)(TPP)(NO3).
AB  - The reaction(s) of nitric oxide (nitrogen monoxide) gas with sublimed layers
      containing the nitrato iron(III) complex Fe(III)(TPP)(eta(2)-O(2)NO) (1, TPP =
      meso-tetraphenyl porphyrinate(2)(-)) leads to formation of several iron porphyrin
      species that are ligated by various nitrogen oxides. The eventual products of
      these low-temperature solid-state reactions are the nitrosyl complex Fe(TPP)(NO),
      the nitro-nitrosyl complex Fe(TPP)(NO(2))(NO), and 1 itself, and the relative
      final quantities of these were functions of the NO partial pressure. It is
      particularly notable that isotope labeling experiments show that the nitrato
      product is not simply unreacted 1 but is the result of a series of
      transformations taking place in the layered material. Thus, the nitrato complex
      formed from solid Fe(TPP)(eta(2)-O(2)NO) maintained under a (15)NO atmosphere was
      found to be the labeled analogue Fe(TPP)(eta(2)-O(2)(15)NO). The reactivities of
      the layered solids are compared to the behaviors of the same species in ambient
      temperature solutions. To interpret the reactions of the labeled nitrogen oxides,
      the potential exchange reactions between N(2)O(3) and (15)NO were examined, and
      complete isotope scrambling was observed between these species under the reaction
      conditions (T = 140 K). Overall it was concluded from isotope labeling
      experiments that the sequence of reactions is initiated by reaction of 1 with NO
      to give the nitrato nitrosyl complex Fe(TPP)(eta(1)-ONO(2))(NO) (2) as an
      intermediate. This is followed by a reaction in the presence of excess NO that is
      equivalent to the loss of the nitrate radical NO(3)(*)( )()to give Fe(TPP)(NO) as
      another transient species. A plausible pathway involving NO attack on the
      coordinated nitrate of 2 resulting in the release of N(2)O(4) concerted with
      electron transfer to the metal center is proposed.

PMID- 15853327
TI  - Photoinduced carbon monoxide migration in a synthetic heme-copper complex.
AB  - Time-resolved infrared (TRIR) flash photolytic techniques have been employed to
      initiate and observe the efficient dissociation of CO from a synthetic heme
      CO/copper complex, [((6)L)Fe(II)(CO)..Cu(I)](+) (2), in CH(3)CN and acetone at
      room temperature. In CH(3)CN, a significant fraction of the photodissociated CO
      molecules transiently bind to copper (nu(CO)(Cu) = 2091 cm(-)(1)) giving
      [((6)L)Fe(II)..Cu(I)(CO)](+) (4), with an observed rate constant, k(1) = 1.5 x
      10(5) s(-)(1). That is followed by a slower direct transfer of CO from the copper
      moiety back to the heme (nu(CO)(Fe) = 1975 cm(-)(1)) with k(2) = 1600 s(-)(1).
      Additional transient absorption (TA) UV-vis spectroscopic experiments have been
      performed monitoring the CO-transfer reaction by following the Soret band. Eyring
      analysis of the temperature-dependent data yields DeltaH(double dagger) = 43.9 kJ
      mol(-)(1) for the 4-to-2 transformation, similar to that for CO dissociation from
      [Cu(I)(tmpa)(CO)](+) in CH(3)CN (DeltaH(double dagger) = 43.6 kJ mol(-)(1)),
      suggesting CO dissociation from copper regulates the binding of small molecules
      to the heme within [((6)L)Fe(II)..Cu(I)](+)(3). Our observations are analagous to
      those observed for the heme(a3)/Cu(B) active site of cytochrome c oxidase, where
      photodissociated CO from the heme(a3) site immediately (ps) transfers to Cu(B)
      followed by millisecond transfer back to the heme.

PMID- 15853328
TI  - Trapping H- bound to the nitrogenase FeMo-cofactor active site during H2
      evolution: characterization by ENDOR spectroscopy.
AB  - We here show that the iron-molybdenum (FeMo)-cofactor of the nitrogenase alpha
      70(Ile) molybdenum-iron (MoFe) protein variant accumulates a novel S = (1)/(2)
      state that can be trapped during the reduction of protons to H(2). (1,2)H-ENDOR
      measurements disclose the presence of two protons/hydrides (H(+/)(-)) whose
      hyperfine tensors have been determined from two-dimensional field-frequency (1)H
      ENDOR plots. The two H(+/)(-) have large isotropic hyperfine couplings, A(iso)(
      )() approximately 23 MHz, which shows they are bound to the cofactor. The favored
      analysis for these plots indicates that the two H(+/)(-) have the same principal
      values, which indicates that they are chemically equivalent. The tensors are
      further related to each other by a permutation of the tensor components, which
      indicates an underlying symmetry of binding relative to the cofactor. At present,
      no model for the structure of the iron-molybdenum (FeMo)-cofactor in the S =
      (1)/(2) state trapped during the reduction of H(+) can be shown unequivocally to
      satisfy all of the constraints generated by the ENDOR analysis. The data
      disfavors any model that involves protonation of sulfides, and thus suggests that
      the intermediate instead contains two chemically equivalent bound hydrides; it
      appears unlikely that these are terminal monohydrides.

PMID- 15853329
TI  - Hybrid nanocapsules: interactions of ABA block copolymers with liposomes.
AB  - Amphiphilic ABA triblock copolymers, such as poly(2-methyloxazoline)-block
      poly(dimethylsiloxan)-block-poly(2-methyloxazoline) (PMOXA-PDMS-PMOXA), form
      vesicular structures. Here, the interaction of these ABA molecules with lipids is
      investigated by electron microscopy, fluorescence spectroscopy, light scattering,
      and differential scanning calorimetry. Our observations suggest the formation of
      homogeneous mixed polymer-lipid composites, independent of preparation method,
      i.e. film hydration, dispersion, or detergent removal. When ABA polymersomes and
      liposomes are mixed, we observed monomer exchanges on a time scale of minutes.
      The possibility of forming mixed structures and the exchanges between preformed
      structures allow the combination of the properties of lipids and polymers such as
      stability and loading encapsulation capacity.

PMID- 15853330
TI  - Environmentally responsive "hairy" nanoparticles: mixed homopolymer brushes on
      silica nanoparticles synthesized by living radical polymerization techniques.
AB  - This article reports on the preparation of environmentally responsive "hairy"
      nanoparticles by growth of mixed poly(tert-butyl acrylate) (PtBA)/polystyrene
      (PS) brushes from silica particles using living radical polymerization techniques
      and subsequent hydrolysis of PtBA to produce amphiphilic mixed poly(acrylic acid)
      (PAA)/PS brushes. Silica particles were synthesized by the Stober process and
      were functionalized with an asymmetric difunctional initiator-terminated
      monolayer. Surface-initiated atom transfer radical polymerization of tBA was
      carried out in the presence of a free initiator. Kinetics study showed that the
      polymerization was well controlled. By cleaving PtBA off the particles, the
      molecular weights of the grafted and free polymers were found to be essentially
      identical. Mixed PtBA/PS brushes were obtained by the nitroxide-mediated radical
      polymerization of styrene from PtBA particles. The M(n) of the grafted PS was
      found to be the same as that of the free PS formed in the solution from the free
      initiator. Amphiphilic mixed PAA/PS brush-coated nanoparticles were synthesized
      from mixed PtBA/PS particles by hydrolysis of PtBA with iodotrimethylsilane.
      Tyndall scattering experiments and (1)H NMR study showed that the mixed PAA/PS
      particles can be dispersed and form a stable suspension in CHCl(3), a selective
      solvent for PS, and also in CH(3)OH, a selective solvent for PAA, demonstrating
      the capability of these hairy nanoparticles to undergo chain reorganization in
      response to environmental changes.

PMID- 15853331
TI  - Ab initio studies on the radiationless decay mechanisms of the lowest excited
      singlet states of 9H-adenine.
AB  - The mechanisms that are responsible for the rapid deactivation of the (1)npi and(
      1)pipi excited singlet states of the 9H isomer of adenine have been investigated
      with multireference ab initio methods (complete-active-space self-consistent
      field (CASSCF) method and second-order perturbation theory based on the CASSCF
      reference (CASPT2)). Two novel photochemical pathways, which lead to conical
      intersections of the S(1) excited potential-energy surface with the electronic
      ground-state surface, have been identified. They involve out-of-plane
      deformations of the six-membered aromatic ring via the twisting of the N(3)C(2)
      and N(1)C(6) bonds. These low-lying conical intersections are separated from the
      minimum energy of the lowest ((1)npi) excited state in the Franck-Condon region
      by very low energy barriers (of the order of 0.1 eV). These properties of the
      S(1) and S(0) potential-energy surfaces explain the unusual laser-induced
      fluorescence spectrum of jet-cooled 9H-adenine, showing sharp structures only in
      a narrow energy interval near the origin, as well as the extreme excess-energy
      dependence of the lifetime of the singlet excited states. It is suggested that
      internal-conversion processes via conical intersections, which are accessed by
      out-of-plane deformation of the six-membered ring, dominate the photophysics of
      the lowest vibronic levels of adenine in the gas phase, while hydrogen
      abstraction photochemistry driven by repulsive (1)pisigma states may become
      competitive at higher excitation energies. These ultrafast excited-state
      deactivation processes provide adenine with a high degree of intrinsic
      photostability.

PMID- 15853332
TI  - Construction of polymeric delta-graph: a doubly fused tricyclic topology.
AB  - A doubly fused tricyclic polymer architecture, corresponding to a delta-graph,
      has been constructed effectively through metathesis polymer cyclization (MPC) of
      an 8-shaped dicyclic polymer precursor having two allyl groups placed at opposite
      positions of the two rings of the 8-shaped structure. The 8-shaped polymer
      precursor has been obtained through the covalent conversion of an electrostatic
      self-assembly (composed of two units of the linear poly(tetrahydrofuran)s,
      poly(THF)s, having pyrrolidinium salt end groups and having a pendant allyl group
      at the middle of the chain, carrying a tetrafunctional carboxylate counteranion)
      by the heating treatment under appropriate dilution to cause the ring-opening
      reaction of pyrrolidinium salt groups by carboxylate anions.

PMID- 15853333
TI  - Asymmetrically modified silica particles: a simple particulate surfactant for
      stabilization of oil droplets in water.
AB  - Spherical silica particles that are able to assemble at a phase boundary of a
      dual-phase mixture of water and an immiscible organic solvent were prepared by a
      partial modification of their surface hydroxyl groups with an alkylsilylation
      agent. Scanning electron microscopic observation of these particles in which
      their remaining surface hydroxyl groups had been selectively modified with
      colloidal gold particles revealed that each particle has an asymmetric surface
      structure: one side of the surface is hydrophilic and the other is hydrophobic.
      We found that these particles could form a micellar structure in water in the
      presence of an organic solution of a toluene/polystyrene mixture. The micellar
      structure was evidenced by formation of golf-ball-like polystyrene particles with
      dimples imprinting morphologies of the hydrophobic part of modified silica
      particles.

PMID- 15853334
TI  - Biomimetic synthesis of antimalarial naphthoquinones.
AB  - The total synthesis of naphthoquinone natural products isolated from the
      Bignoniaceae plant family is described. Pinnatal, isopinnatal, sterekunthals A
      and B, pyranokunthones A and B, and anthrakunthone have been prepared along the
      lines of a biosynthetic proposal involving pericyclic reactions as key steps. The
      first case of catalysis in oxa 6pi electrocyclizations is reported.

PMID- 15853335
TI  - A highly enantio- and diastereoselective catalytic intramolecular Stetter
      reaction.
AB  - A highly enantio- and diastereoselective intramolecular Stetter reaction has been
      developed. Subjection of alpha,alpha-disubstituted Michael acceptors to an
      asymmetric intramolecular Stetter reaction results in a highly enantioselective
      conjugate addition and a diastereoselective proton transfer. Available evidence
      suggests the diastereoselective protonation occurs via intramolecular delivery to
      the sterically more hindered face of the enolate. The scope of the trisubstituted
      Michael acceptors has been examined and found to be broad with respect to the
      size of the alpha-substituent and nature of the Michael acceptor. Aliphatic and
      aromatic aldehydes were examined and found to afford the desired product in good
      overall yield with high enantio- and diastereoselectivity.

PMID- 15853336
TI  - Why do the heavy-atom analogues of acetylene E2H2 (E = Si-Pb) exhibit unusual
      structures?
AB  - DFT calculations at BP86/QZ4P have been carried out for different structures of
      E(2)H(2) (E = C, Si, Ge, Sn, Pb) with the goal to explain the unusual equilibrium
      geometries of the heavier group 14 homologues where E = Si-Pb. The global energy
      minima of the latter molecules have a nonplanar doubly bridged structure A
      followed by the singly bridged planar form B, the vinylidene-type structure C,
      and the trans-bent isomer D1. The energetically high-lying trans-bent structure
      D2 possessing an electron sextet at E and the linear form HEEH, which are not
      minima on the PES, have also been studied. The unusual structures of E(2)H(2) (E
      = Si-Pb) are explained with the interactions between the EH moieties in the
      (X(2)Pi) electronic ground state which differ from C(2)H(2), which is bound
      through interactions between CH in the a(4)Sigma(-) excited state. Bonding
      between two (X(2)Pi) fragments of the heavier EH hydrides is favored over the
      bonding in the a(4)Sigma(-) excited state because the X(2)Pi --> a(4)Sigma(-)
      excitation energy of EH (E = Si-Pb) is significantly higher than for CH. The
      doubly bridged structure A of E(2)H(2) has three bonding orbital contributions:
      one sigma bond and two E-H donor-acceptor bonds. The singly bridged isomer B also
      has three bonding orbital contributions: one pi bond, one E-H donor-acceptor
      bond, and one lone-pair donor-acceptor bond. The trans-bent form D1 has one pi
      bond and two lone-pair donor-acceptor bonds, while D2 has only one sigma bond.
      The strength of the stabilizing orbital contributions has been estimated with an
      energy decomposition analysis, which also gives the bonding contributions of the
      quasi-classical electrostatic interactions.

PMID- 15853337
TI  - The reaction of tetrakis(dimethylamido)titanium with self-assembled
      alkyltrichlorosilane monolayers possessing -OH, -NH2, and -CH3 terminal groups.
AB  - The reactions of tetrakis(dimethylamido)titanium, Ti[N(CH(3))(2)](4), with
      alkyltrichlorosilane self-assembled monolayers (SAMs) terminated by -OH, -NH(2),
      and -CH(3) groups have been investigated with X-ray photoelectron spectroscopy
      (XPS). For comparison, a chemically oxidized Si surface, which serves as the
      starting point for formation of the SAMs, has also been investigated. In this
      work, we examined the kinetics of adsorption, the spatial extent, and
      stoichiometry of the reaction. Chemically oxidized Si has been found to be the
      most reactive surface examined here, followed by the -OH, -NH(2), and -CH(3)
      terminated SAMs, in that order. On all surfaces, the reaction of
      Ti[N(CH(3))(2)](4) was relatively facile, as evidenced by a rather weak
      dependence of the initial reaction probability on substrate temperature (T(s) = 
      50 to 110 degrees C), and adsorption could be described by first-order
      Langmuirian kinetics. The use of angle-resolved XPS demonstrated clearly that the
      anomalous reactivity of the -CH(3) terminated SAM could be attributed to reaction
      of Ti[N(CH(3))(2)](4) at the SAM/SiO(2) interface. Reaction on the -NH(2)
      terminated SAM proved to be the "cleanest", where essentially all of the
      reactivity could be associated with the terminal amine group. In this case, we
      found that approximately one Ti[N(CH(3))(2)](4) adsorbed per two SAM molecules.
      On all surfaces, there was significant loss of the N(CH(3))(2) ligand,
      particularly at high substrate temperatures, T(s) = 110 degrees C. These results
      show for the first time that it is possible to attach a transition metal
      coordination complex from the vapor phase to a surface with an appropriately
      functionalized self-assembled monolayer.

PMID- 15853338
TI  - Organolanthanide-catalyzed synthesis of phosphine-terminated polyethylenes. Scope
      and mechanism.
AB  - Primary and secondary phosphines are investigated as chain-transfer agents for
      organolanthanide-mediated olefin polymerization. Ethylene polymerizations were
      carried out with [Cp'(2)LnH](2) and Cp'(2)LnCH(SiMe(3))(2) (Cp' = eta(5)
      Me(5)C(5); Ln = La, Sm, Y, Lu) precatalysts in the presence of dicyclohexyl-,
      diisobutyl-, diethyl-, diphenyl-, cyclohexyl-, and phenylphosphine. In the
      presence of secondary phosphines, high polymerization activities (up to 10(7) g
      of polymer/(mol of Ln.atm ethylene.h)) and narrow product polymer
      polydispersities are observed. For lanthanocene-mediated ethylene
      polymerizations, the phosphine chain-transfer efficiency correlates with the rate
      of Ln-CH(SiMe(3))(2) protonolysis by the same phosphines and follows the trend
      H(2)PPh >> H(2)PCy > HPPh(2) > HPEt(2) approximately HP(i)()Bu(2) > HPCy(2).
      Under the conditions investigated, dicyclohexylphosphine is not an efficient
      chain-transfer agent for Cp'(2)LaPCy(2)- and Cp'(2)YPCy(2)-mediated ethylene
      polymerizations. Diisobutylphosphine and diethylphosphine are efficient chain
      transfer agents for Cp'(2)La-mediated polymerizations; however, phosphine chain
      transfer does not appear to be competitive with other chain-transfer pathways in
      Cp'(2)Y-mediated polymerizations involving diisobutylphosphine. Regardless of the
      lanthanide metal, diphenylphosphine is an efficient chain-transfer agent for
      ethylene polymerization. Polymerizations conducted in the presence of primary
      phosphines produce only low-molecular-weight products. Thus, Cp'(2)Y-mediated
      ethylene polymerizations conducted in the presence of phenylphosphine and
      cyclohexylphosphine produce low-molecular-weight phenylphosphine- and
      cyclohexylphosphine-capped oligomers, respectively. For Cp'(2)YPPh(2)-mediated
      ethylene polymerizations, a linear relationship is observed between M(n) and
      [diphenylphosphine](-)(1), consistent with a phosphine protonolytic chain
      transfer mechanism.

PMID- 15853339
TI  - Carbon-fluorine bond activation coupled with carbon-carbon bond formation at
      iridium. Confirmation of complete kinetic diastereoselectivity at the new carbon
      stereocenter by intramolecular trapping using vinyl as the migrating group.
AB  - The iridium(perfluoropropyl)(vinyl) complex CpIr(PMe(3))(n-C(3)F(7))(CH=CH(2))
      (5) has been prepared. It has been characterized by X-ray crystallography, and
      its ground state conformation in solution has been determined by (19)F{(1)H}
      HOESY NMR studies. It reacts with the weak acid lutidinium iodide to afford the
      eta(1)-allylic complex CpIr(PMe(3))((Z)-CH(2)CH=CFC(2)F(5))I (6), which has also
      been characterized crystallographically. The mechanism of C-F bond activation and
      C-C bond formation leading to 6 has been elucidated in detail by studying the
      reaction of 5 with lutidinium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate
      [LutH(+)B(ArF)(4)(-)], containing a weakly coordinating counteranion. The main
      kinetic product of this reaction, determined by (19)F{(1)H} HOESY studies at -50
      degrees C, is the endo-CpIr(PMe(3))(anti-eta(3)-CH(2)CHCFCF(2)CF(3))[B(ArF)(4)]
      diastereomer 9, along with a small amount of the exo-syn-isomer 8. Isomer 9
      rearranges at -20 degrees C to its exo-anti isomer 7, and subsequently to the
      thermodynamically favored exo-syn-isomer 8, which has been isolated and
      crystallographically characterized. Complex 8 reacts with iodide to afford
      complex6. On the basis of the unambiguously defined kinetically controlled
      stereochemistry of 9 and 8, a detailed mechanism for the C-F activation/C-C
      coupling reaction is proposed, the principal conclusion of which is that C-F
      activation is completely diastereoselective.

PMID- 15853341
TI  - Ag4V2O6F2: an electrochemically active and high silver density phase.
AB  - Low-temperature hydrothermal techniques were used to synthesize single crystals
      of Ag(4)V(2)O(6)F(2). This previously unreported oxide fluoride phase was
      characterized by single-crystal X-ray diffraction and IR spectroscopy and was
      also evaluated as a primary lithium battery cathode. Crystal data: monoclinic,
      space group P2(1)/n (No. 14), with a = 8.4034(4) A, b = 10.548(1) A, c =
      12.459(1) A, beta = 90.314(2) degrees , and Z = 4. Ag(4)V(2)O(6)F(2) (SVOF)
      exhibits two characteristic regions within the discharge curve, an upper plateau
      at 3.5 V, and a lower sloped region around 2.3 V from reduction of the vanadium
      oxide fluoride framework. The material has a nominal capacity of 251 mAh/g, with
      148 mAh/g above 3 V. The upper discharge plateau at 3.5 V is nearly 300 mV over
      the silver reduction potential of the commercial primary battery material,
      Ag(2)V(4)O(11) (SVO).

PMID- 15853340
TI  - Structures, electronic states, photoluminescence, and carrier transport
      properties of 1,1-disubstituted 2,3,4,5-tetraphenylsiloles.
AB  - The excellent electroluminescent (EL) properties of 1,1-disubstituted 2,3,4,5
      tetraphenylsiloles, 1-methyl-1,2,3,4,5-pentaphenylsilole (MPPS), and 1,1,2,3,4,5
      hexaphenylsilole (HPS) have been found. Despite some studies devoted to these
      materials, very little is known about the real origin of their unique EL
      properties. Therefore, we investigated the structures, photoluminescence (PL),
      and charge carrier transport properties of 1,1-disubstituted 2,3,4,5
      tetraphenylsiloles as well as the effect of substituents on these
      characteristics. The single crystals of the three siloles involving 1,1-dimethyl
      2,3,4,5-tetraphenylsilole (DMTPS), MPPS, and HPS were grown and their crystal
      structures were determined by X-ray diffraction. Three siloles have nonplanar
      molecular structures. The substituents at 1,1-positions enhance the steric
      hindrance and have predominant influence on the twisted degree of phenyl groups
      at ring carbons. This nonplanar structure reduces the intermolecular interaction
      and the likelihood of excimer formation, and increases PL efficiency in the solid
      state. The silole films show high fluorescence quantum yields (75-85%), whereas
      their dilute solutions exhibit a faint emission. The electronic structures of the
      three siloles were investigated using quantum chemical calculations. The highest
      occupied molecular orbitals (HOMOs) and the lowest unoccupied molecular orbitals
      (LUMOs) are mainly localized on the silole ring and two phenyl groups at 2,5
      positions in all cases, while the LUMOs have a significant orbital density at two
      exocyclic Si-C bonds. The extremely theoretical studies of luminescent properties
      were carried out. We calculated the nonradiative decay rate of the first excited
      state as well as the radiative one. It is found that the faint emission of DMTPS
      in solutions mainly results from the huge nonradiative decay rate. In solid
      states, molecular packing can remarkably restrict the intramolecular rotation of
      the peripheral side phenyl ring, which has a large contribution to the
      nonradiative transition process. This explains why the 1,1-disubstituted 2,3,4,5
      tetraphenylsiloles in the thin films exhibit high fluorescence quantum yields.
      The charge carrier mobilities of the MPPS and HPS films were measured using a
      transient EL technique. We obtained a mobility of 2.1 x 10(-)(6) cm(2)/V.s in the
      MPPS film at an electric field of 1.2 x 10(6) V/cm. This mobility is comparable
      to that of Alq(3), which is one of the most extensively used electron transport
      materials in organic light-emitting diodes (LEDs), at the same electric field.
      The electron mobility of the HPS film is about approximately 1.5 times higher
      than that of the MPPS film. To the best of our knowledge, this kind of material
      is one of the most excellent emissive materials that possess both high charge
      carrier mobility and high PL efficiency in the solid states simultaneously. The
      excellent EL performances of MPPS and HPS are presumably ascribed to these
      characteristics.

PMID- 15853342
TI  - Pyrolysis of mesoporous silica-immobilized 1,3-diphenylpropane. Impact of pore
      confinement and size.
AB  - Mesoporous silicas such as SBA-15 and MCM-41 are being actively investigated for
      potential applications in catalysis, separations, and synthesis of nanostructured
      materials. A new method for functionalizing these mesoporous silicas with
      aromatic phenols is described. The resulting novel hybrid materials possess silyl
      aryl ether linkages to the silica surface that are thermally stable to ca. 550
      degrees C, but can be easily cleaved at room temperature with aqueous base for
      quantitative recovery of the organic moieties. The materials have been
      characterized by nitrogen physisorption, FTIR, NMR, and quantitative analysis of
      surface coverages. The maximum densities of 1,3-diphenylpropane (DPP) molecules
      that could be grafted to the surface were less than those measured on a
      nonporous, fumed silica (Cabosil) and were also found to decrease as a function
      of decreasing pore size (5.6-1.7 nm). This is a consequence of steric congestion
      in the pores that is magnified at the smaller pore sizes, consistent with
      parallel studies conducted using a conventional silylating reagent, 1,1,3,3
      tetramethyldisilazane. Pyrolysis of the silica-immobilized DPP revealed that pore
      confinement leads to enhanced rates and altered product selectivity for this free
      radical reaction compared with the nonporous silica, and the rates and
      selectivities also depended on pore size. The influence of confinement is
      discussed in terms of enhanced encounter frequencies for bimolecular reaction
      steps and pore surface curvature that alters the accessibility and resultant
      selectivity for hydrogen transfer steps.

PMID- 15853343
TI  - Liquid hydrogen in protonic chabazite.
AB  - Due to its fully reversible nature, H(2) storage by molecular adsorption could
      represent an advantage with respect to dissociative processes, where kinetic
      effects during the charging and discharging processes are present. A drawback of
      this strategy is represented by the extremely weak interactions that require low
      temperature and high pressure. High surface area materials hosting polarizing
      sites can represent a viable way toward more favorable working conditions. Of
      these, in this contribution, we have studied hydrogen adsorption in a series of
      zeolites using volumetric techniques and infrared spectroscopy at 15 K. We have
      found that in H-SSZ-13 zeolite the cooperative role played by high surface area,
      internal wall topology, and presence of high binding energy sites (protons)
      allows hydrogen to densify inside the nanopores at favorable temperature and
      pressure conditions.

PMID- 15853344
TI  - The formation mechanism of a textured ceramic of thermoelectric
      [Ca2CoO3](0.62)[CoO2] on beta-Co(OH)2 templates through in situ topotactic
      conversion.
AB  - We investigated the formation mechanism of thermoelectric
      [Ca(2)CoO(3)](0.62)[CoO(2)] (CCO) on beta-Co(OH)(2) templates with maintained
      orientations by identifying the intermediate phases and specifying the
      relationship between their crystallographic orientations. We mixed beta-Co(OH)(2)
      templates with the complementary reactant CaCO(3) and prepared a compact by tape
      casting, with the developed (001) plane of the templates aligned along the
      casting plane. High-temperature XRD of the compact revealed that beta-Co(OH)(2)
      decomposed into Co(3)O(4) by 873 K, and Co(3)O(4) reacted with CaO to form CCO by
      1193 K via the formation of the newly detected intermediate phase beta
      Na(x)()CoO(2)-type Ca(x)()CoO(2) at 913-973 K. Pole figure measurements and SEM
      and TEM observations revealed that the relationship between the crystallographic
      planes was (001) beta-Co(OH)(2)//{111} Co(3)O(4)//(001) Ca(x)()CoO(2)//(001) CCO.
      The crystal structures of the four materials possess the common CoO(2) layer (or
      similar), which is composed of edge-sharing CoO(6) octahedra, parallel to the
      planes. The cross-sectional HRTEM analysis of an incompletely reacted specimen
      showed transient lattice images from Ca(x)()CoO(2) into CCO, in which every other
      CoO(2) layer of Ca(x)()CoO(2) was preserved. Thus, it was demonstrated that a
      textured CCO ceramic is produced through a series of in situ topotactic
      conversion reactions with a preserved CoO(2) layer of its template.

PMID- 15853345
TI  - Multifunctionality and crystal dynamics of a highly stable, porous metal-organic
      framework [Zn4O(NTB)2].
AB  - A porous metal-organic framework [Zn(4)O(NTB)(2)].3DEF.EtOH (1), in which (3,6)
      connected nets are doubly interpenetrated to generate curved three-dimensional
      channels, has been prepared. Framework 1 exhibits high permanent porosity
      (Langmuir surface area, 1121 m(2)/g; pore volume, 0.51 cm(3)/cm(3)), high thermal
      stability (up to 430 degrees C), high hydrogen adsorption capacity (1.9 wt % at
      77 K and 1 atm), selective organic guest binding ability (K(f)()( )(): MeOH >
      pyridine > benzene > dodecane), and guest-dependent blue luminescence
      (lambda(max) depending on guest identity). Most interestingly, the framework
      sustains single crystallinity even at 400 degrees C and 10(-)(5) Torr, and the
      framework components undergo reversible dynamics, mainly rotational motion, in
      response to removal and rebinding of the guest molecules.

PMID- 15853346
TI  - Reversible molecular switching of ruthenium bis(bipyridyl) groups bonded to
      oligothiophenes: effect on electrochemical and spectroscopic properties.
AB  - We report the preparation of complexes in which ruthenium(II) bis(bipyridyl)
      groups are coordinated to oligothiophenes via a diphenylphosphine linker and a
      thienyl sulfur (P,S bonding) to give [Ru(bpy)(2)PT(3)-P,S](PF(6))(2) (bpy = 2,2'
      bipyridyl, PT(3) = 3'-(diphenylphosphino)-2,2':5',2' '-terthiophene),
      [Ru(bpy)(2)PMeT(3)-P,S](PF(6))(2) (PMeT(3) = 3'-(diphenylphosphino)-5-methyl
      2,2':5',2' '-terthiophene), [Ru(bpy)(2)PMe(2)T(3)-P,S](PF(6))(2) (PMe(2)T(3) =
      5,5' '-dimethyl-3'-(diphenylphosphino)-2,2':5',2' '-terthiophene), and
      [Ru(bpy)(2)PDo(2)T(5)-P,S](PF(6))(2) (PDo(2)T(5) = 3,3' '' '-didodecyl-3' '
      diphenylphosphino-2,2':5',2' ':5' ',2' '':5' '',2' '' '-pentathiophene). These
      complexes react with base, resulting in the complexes [Ru(bpy)(2)PT(3)-P,C]PF(6),
      [Ru(bpy)(2)PMeT(3)-P,C]PF(6), [Ru(bpy)(2)PMe(2)T(3)-P,C]PF(6), and
      [Ru(bpy)(2)PDo(2)T(5)-P,C]PF(6), where the thienyl carbon is bonded to ruthenium
      (P,C bonding). The P,C complexes revert back to the P,S bonding mode by reaction
      with acid; therefore, metal-thienyl bonding is reversibly switchable. The effect
      of interaction of the metal groups in the different bonding modes with the
      thienyl backbone is reflected by changes in alignment of the thienyl rings in the
      solid-state structures of the complexes, the redox potentials, and the pi --> pi
      transitions in solution. Methyl substituents attached to the terthiophene groups
      allow observation of the effect of these substituents on the conformational and
      electronic properties and aid in assignments of the electrochemical data. The
      PT(n)() ligands bound in P,S and P,C bonding modes also alter the electrochemical
      and spectroscopic properties of the ruthenium bis(bipyridyl) group. Both bonding
      modes result in quenching of the oligothiophene luminescence. Weak, short-lived
      Ru --> bipyridyl MLCT-based luminescence is observed for [Ru(bpy)(2)PDo(2)T(5)
      P,S](PF(6))(2), [Ru(bpy)(2)PT(3)-P,C]PF(6), [Ru(bpy)(2)PMeT(3)-P,C]PF(6), and
      [Ru(bpy)(2)PMe(2)T(3)-P,C]PF(6), and no emission is observed for the alternate
      bonding mode of each complex.

PMID- 15853347
TI  - Solid-state composite electrolyte LiI/3-hydroxypropionitrile/SiO2 for dye
      sensitized solar cells.
AB  - A new compound, LiI(3-hydroxypropionitrile)(2), is reported here. According to
      its single-crystal structure (C2/c), this compound has 3-D transporting paths for
      iodine. Further ab initio calculation shows that the activation energy for
      diffusion of iodine (0.73 eV) is much lower than that of lithium ion (8.39 eV)
      within the lattice. Such a mono-ion transport feature is favorable as solid
      electrolyte to replace conventional volatile organic liquid electrolytes used in
      dye-sensitized solar cells (DSSC). LiI and 3-hydroxypropionitrile (HPN) can form
      a series of solid electrolytes. The highest ambient conductivity is 1.4 x 10(
      )(3) S/cm achieved for LiI(HPN)(4). However, it tends to form large crystallites
      and leads to poor filling and contact within porous TiO(2) electrodes in DSSC.
      Such a drawback can be greatly improved by introducing micrometer-sized and
      nanosized SiO(2) particles into the solid electrolyte. It is helpful not only in
      enhancing the conductivity but also in improving the interfacial contact greatly.
      Consequently, the light-to-electricity conversion efficiency of 5.4% of a DSSC
      using LiI(HPN)(4)/15 wt % nano-SiO(2) was achieved under AM 1.5 simulated solar
      light illumination. Due to the low cost, easy fabrication, and relatively high
      conversion efficiency, the DSSC based on this new solid-state composite
      electrolyte is promising for practical applications.

PMID- 15853348
TI  - Large structure rearrangement of colicin ia channel domain after membrane binding
      from 2D 13C spin diffusion NMR.
AB  - One of the main mechanisms of membrane protein folding is by spontaneous
      insertion into the lipid bilayer from the aqueous environment. The bacterial
      toxin, colicin Ia, is one such protein. To shed light on the conformational
      changes involved in this dramatic transfer from the polar to the hydrophobic
      milieu, we carried out 2D magic-angle spinning (13)C NMR experiments on the water
      soluble and membrane-bound states of the channel-forming domain of colicin Ia.
      Proton-driven (13)C spin diffusion spectra of selectively (13)C-labeled protein
      show unequivocal attenuation of cross-peaks after membrane binding. This
      attenuation can be assigned to distance increases but not reduction of the
      diffusion coefficient. Analysis of the statistics of the interhelical and
      intrahelical (13)C-(13)C distances in the soluble protein structure indicates
      that the observed cross-peak reduction is well correlated with a high percentage
      of short interhelical contacts in the soluble protein. This suggests that colicin
      Ia channel domain becomes open and extended upon membrane binding, thus
      lengthening interhelical distances. In comparison, cross-peaks with similar
      intensities between the two states are dominated by intrahelical contacts in the
      soluble state. This suggests that the membrane-bound structure of colicin Ia
      channel domain may be described as a "molten globule", in which the helical
      secondary structure is retained while the tertiary structure is unfolded. This
      study demonstrates that (13)C spin diffusion NMR is a valuable tool for obtaining
      qualitative long-range distance constraints on membrane protein folding.

PMID- 15853349
TI  - Solution 1H NMR characterization of the distal H-bond network and the effective
      axial field in the resting-state, high-spin ferric, substrate-bound complex of
      heme oxygenase from N. meningitidis.
AB  - The solution (1)H 1D and 2D NMR spectra of the high-spin ferric, resting-state,
      substrate-bound complex of heme oxygenase, HO, from the pathological bacterium N.
      meningitidis have been investigated to assess the prospects for definitive
      assignment of hyperfine shifted and relaxed residue protons and the
      interpretation of those shifts in terms of the anisotropy and orientation of the
      paramagnetic susceptibility tensor, chi. Appropriately tailored 1D/2D NMR data,
      together with analyses of paramagnetic relaxation and a preliminary estimate of
      the magnetic anisotropy, reveal a chi that is axially anisotropic and oriented
      along the Fe-His vector. Together with T(-)(2) dependence of the shifts,
      Deltachi(ax) yields a zero-field splitting constant, D = 9.1 cm(-)(1), which is
      expected to serve as a very sensitive probe of H-bond interactions between the
      iron-ligated water and a series of distal ordered water molecules implicated in
      the mechanism of HO action. The side chains, Gln49 and His53, involved in the
      stabilization of catalytically relevant water molecules, were found to exhibit
      orientations rotated by 180 degrees about the beta-gamma bonds in solution
      relative to those in the crystal. The implication of these reorientations on the
      details of the distal H-bond network is discussed. The H-bond donor strengths of
      Gln 49 and His53 were found to respond appropriately to H-bond donor (water)
      versus H-bond acceptor (cyanide) iron ligands. Very slow NH exchange for the N
      terminal portion of the distal helix suggest that an intrinsically "unstable"
      distal helix may be valid only for the C-terminal portion.

PMID- 15853350
TI  - Electrochemically controlled hydrogen bonding. Nitrobenzenes as simple redox
      dependent receptors for arylureas.
AB  - Reduction of nitrobenzene derivatives in the presence of arylureas in aprotic
      solvents results in large positive shifts in potential of the nitrobenzene(0/)(-)
      cyclic voltammetry wave with little change in wave shape. This behavior is
      indicative of reversible hydrogen bonding between nitrobenzene radical anions and
      arylureas. Computer fitting of the cyclic voltammetry of 4-nitroaniline, NA, plus
      1,3-diphenylurea in DMF shows essentially no binding between urea and NA in the
      oxidized state (K(ox) < 1 M(-)(1)), but very strong binding in the reduced state
      (K(red) = 8 x 10(4) M(-)(1)), along with very rapid rates of hydrogen bond
      formation (k(f)'s approximately 10(8)-10(10) M(-)(1) s(-)(1)), making this system
      a fast on/off redox switch.

PMID- 15853351
TI  - A ruler for determining the position of proteins in membranes.
AB  - Both the oxygen diffusion rate and the oxygen solubility vary with depth into the
      interior of biological membranes. The product of these two gradients generates a
      single gradient, a permeability gradient, which is a smooth continuous function
      of the distance from the center of the membrane. Using electron paramagnetic
      resonance and the spin-probe method, the relaxation gradient of oxygen, which is
      directly proportional to the permeability gradient, is the quantity that can be
      directly measured in membranes under physiological conditions. The gradient
      obtained provides a calibrated ruler for determining the membrane depth of
      residues either from loop regions of membrane-binding proteins or from the
      membrane-exposed residues of transmembrane proteins. We have determined the
      relaxation gradient of oxygen in zwitterionic and anionic phospholipid membranes
      by attaching a single nitroxide probe to a transmembrane alpha-helical
      polypeptide at specific residues. The peptide ruler was used to determine the
      depth of penetration of the calcium-binding loops of the C2 domain of cytosolic
      phospholipase A(2). The positions of selected residues of this membrane-binding
      protein that penetrate into the membrane, determined using this ruler, compared
      favorably with previous determinations using more complex methods. The relaxation
      gradient constrains the possible values of the membrane-dependent oxygen
      concentration and the oxygen diffusion gradients. The average oxygen diffusion
      coefficient is estimated to be at least 2-fold smaller in the membrane than that
      in water.

PMID- 15853352
TI  - AT base pair anions versus (9-methyl-A)(1-methyl-T) base pair anions.
AB  - The anionic base pairs of adenine and thymine, (AT)(-), and 9-methyladenine and 1
      methylthymine, (MAMT)(-), have been investigated both theoretically and
      experimentally in a complementary, synergistic study. Calculations on (AT)(-)
      found that it had undergone a barrier-free proton transfer (BFPT) similar to that
      seen in other dimer anion systems and that its structural configuration was
      neither Watson-Crick (WC) nor Hoogsteen (HS). The vertical detachment energy
      (VDE) of (AT)(-) was determined by anion photoelectron spectroscopy and found to
      be in agreement with the VDE value predicted by theory for the BFPT mechanism. An
      AT pair in DNA is structurally immobilized into the WC configuration, in part, by
      being bonded to the sugars of the double helix. This circumstance was mimicked by
      methylating the sites on both A and T where these sugars would have been tied,
      viz., 9-methyladenine and 1-methylthymine. Calculations found no BFPT in (MAMT)(
      ) and a resulting (MAMT)(-) configuration that was either HS or WC, with the
      configurations differing in stability by ca. 2 kcal/mol. The photoelectron
      spectrum of (MAMT)(-) occurred at a completely different electron binding energy
      than had (AT)(-). Moreover, the VDE value of (MAMT)(-) was in agreement with that
      predicted by theory. The configuration of (MAMT)(-) and its lack of electron
      induced proton transfer are inter-related. While there may be other pathways for
      electron-induced DNA alterations, BFPT in the WC/HS configurations of (AT)(-) is
      not feasible.

PMID- 15853353
TI  - Solid-state NMR and quantum chemical investigations of 13Calpha shielding tensor
      magnitudes and orientations in peptides: determining phi and psi torsion angles.
AB  - We report the experimental determination of the (13)C(alpha) chemical shift
      tensors of Ala, Leu, Val, Phe, and Met in a number of polycrystalline peptides
      with known X-ray or de novo solid-state NMR structures. The 700 Hz dipolar
      coupling between (13)C(alpha) and its directly bonded (14)N permits extraction of
      both the magnitude and the orientation of the shielding tensor with respect to
      the C(alpha)-N bond vector. The chemical shift anisotropy (CSA) is recoupled
      under magic-angle spinning using the SUPER technique (Liu et al., J. Magn. Reson.
      2002, 155, 15-28) to yield quasi-static chemical shift powder patterns. The
      tensor orientation is extracted from the (13)C-(14)N dipolar modulation of the
      powder line shapes. The magnitudes and orientations of the experimental
      (13)C(alpha) chemical shift tensors are found to be in good accord with those
      predicted from quantum chemical calculations. Using these principal values and
      orientations, supplemented with previously measured tensor orientations from
      (13)C-(15)N and (13)C-(1)H dipolar experiments, we are able to predict the (phi,
      psi, chi(1)) angles of Ala and Val within 5.8 degrees of the crystallographic
      values. This opens up a route to accurate determination of torsion angles in
      proteins based on shielding tensor magnitude and orientation information using
      labeled compounds, as well as the structure elucidation of noncrystalline organic
      compounds using natural abundance (13)C NMR techniques.

PMID- 15853354
TI  - Orientational properties of stretched polystyrene gels in organic solvents and
      the suppression of their residual 1H NMR signals.
AB  - While residual dipolar couplings (RDCs) are an established method in high
      resolution biomolecular NMR, their use for structure determination of small
      molecules in organic solvents is limited by the alignment media available. Only
      recently stretched polystyrene (PS) gels were introduced for the measurement of
      RDCs on small compounds that allowed urgently needed free scalability of the
      induced anisotropy. Here, the properties of such stretched PS gels in different
      organic solvents as well as for different magnetic field strengths and
      temperatures are studied and practical NMR-spectroscopic aspects are discussed.

PMID- 15853355
TI  - Competing simple cleavage reactions: the elimination of alkyl radicals from amine
      radical cations.
AB  - Two different alkyl radicals can be expelled when unsymmetrical aliphatic amine
      radical cations undergo C-C bond cleavage. The branching ratio is strongly
      dependent on the internal energy of the reactant, even when the competition
      involves loss of closely related alkyl radicals. In mass spectrometers, the rate
      of loss of the smaller radical (excepting methyl) always exceeds the rate of loss
      of the larger close to threshold. The preference is reversed for the more highly
      energized ions that react in the ion source, demonstrating that the rate of loss
      of the larger radical rises much more rapidly with increasing internal energy
      than does the rate of loss of the smaller radical. This result is not easily
      reconciled with a simple RRKM model, given the expected strong resemblance
      between the transition states involved, whereas it agrees well with a description
      based on variational transition state theory. The heats of formation of the
      products determined with the G3 composite ab initio method show that loss of the
      smaller radical is without exception the more favorable reaction. The relative
      rates of the competing C-C bond cleavage reactions of the metastable ions vary
      with the number of degrees of freedom of the reactant, with the critical energy
      of the reaction, and with the difference between the heats of formation of the
      products. The presence of intermediate energy barriers when cleavage occurs at a
      branching point can give rise to variations in relative rates that are not easily
      interpreted.

PMID- 15853356
TI  - Experimental study of the interplay between long-range electron transfer and
      redox probe permeation at self-assembled monolayers: evidence for potential
      induced ion gating.
AB  - Evidence for the competition between long-range electron transfer across self
      assembled monolayers (SAMs) and incorporation of the redox probe into the film is
      reported for the electroreduction of Ru(NH(3)) at hydroxyl- and carboxylic-acid
      terminated SAMs on a mercury electrode, by using electrochemical techniques that
      operate at distinct time scales. Two limiting voltammetric behaviors are
      observed, consistent with a diffusion control of the redox process at
      mercaptophenol-coated electrodes and a kinetically controlled electron transfer
      reaction in the presence of neutral HS-(CH(2))(10)-COOH and HS-(CH(2))(n)()
      CH(2)OH (n = 3, 5, and 10) SAMs. The monolayer thickness dependence of the
      standard heterogeneous electron transfer rate constant shows that the electron
      transfer plane for the reduction of Ru(NH(3)) at hydroxyl-terminated SAMs is
      located outside the film | solution interface at short times. However, long time
      scale experiments provide evidence for the occurrence of potential-induced gating
      of the adsorbed structure in some of the monolayers studied, which takes the form
      of a chronoamperometric spike. Redox probe permeation is shown to be a
      kinetically slow process, whose activation strongly depends on redox probe
      concentration, applied potential, and chemical composition of the intervening
      medium. The obtained results reveal that self-assembled monolayers made of
      mercaptobutanol and mercaptophenol preserve their electronic barrier properties
      up to the reductive desorption potential of a fully grown SAM, whereas those of
      mercaptohexanol, mercaptoundecanol, and mercaptoundecanoic acid undergo an
      order/disorder transition below a critical potential, which facilitates the
      approach of the redox probe toward the electrode surface.

PMID- 15853357
TI  - The microenvironment effect on the generation of reactive oxygen species by Pd
      bacteriopheophorbide.
AB  - Generation of reactive oxygen species (ROS) is the hallmark of important
      biological processes and photodynamic therapy (PDT), where ROS production results
      from in situ illumination of certain dyes. Here we test the hypothesis that the
      yield, fate, and efficacy of the species evolved highly depend on the dye's
      environment. We show that Pd-bacteriopheophorbide (Pd-Bpheid), a useful reagent
      for vascular targeted PDT (VTP) of solid tumors, which has recently entered into
      phase II clinical trials under the code name WST09 (trade name TOOKAD), forms
      appreciable amounts of hydroxyl radicals, superoxide radicals, and probably
      hydrogen peroxide in aqueous medium but not in organic solvents where singlet
      oxygen almost exclusively forms. Evidence is provided by pico- and nanosecond
      time-resolved spectroscopies, ESR spectroscopy with spin-traps, time-resolved
      singlet oxygen phosphorescence, and chemical product analysis. The quantum yield
      for singlet oxygen formation falls from approximately 1 in organic solvents to
      approximately 0.5 in membrane-like systems (micelles or liposomes), where
      superoxide and hydroxyl radicals form at a minimal quantum yield of 0.1%.
      Analysis of photochemical products suggests that the formation of oxygen radicals
      involves both electron and proton transfer from (3)Pd-Bpheid at the
      membrane/water interface to a colliding oxygen molecule, consequently forming
      superoxide, then hydrogen peroxide, and finally hydroxyl radicals, with no need
      for metal catalysis. The ability of bacteriochlorophyll (Bchl) derivatives to
      form such radicals upon excitation at the near infrared (NIR) domain opens new
      avenues in PDT and research of redox regulation in animals and plants.

PMID- 15853358
TI  - Quercetin-dependent inhibition of nitration induced by peroxidase/H2O2/nitrite
      systems in human saliva and characterization of an oxidation product of quercetin
      formed during the inhibition.
AB  - Local pH in the oral cavity can decrease to below 7 at the site where acid
      producing bacteria are proliferating. Effects of pH on nitration of 4
      hydroxyphenylacetic acid were studied using dialyzed human saliva. Dialyzed
      saliva nitrated 4-hydroxyphenylacetic acid to 4-hydroxy-3-nitrophenylacetic acid
      in the presence of nitrite and H(2)O(2). The rate of the nitration was dependent
      on pH, and the maximal rate was observed between pH 5.5 and 7.2. The optimum pH
      seemed to reflect rates of formation of nitrogen dioxide and 4
      hydroxyphenylacetic acid radicals. Quercetin inhibited the nitration. The
      quercetin-dependent inhibition might be due to scavenging of nitrogen dioxide and
      4-hydroxyphenylacetic acid radicals, which were formed by salivary peroxidase
      dependent oxidation of nitrite and 4-hydroxyphenylacetic acid, respectively, and
      competition with nitrite and 4-hydroxyphenylacetic acid for peroxidase in saliva.
      An oxidation product of quercetin was formed during inhibition of the nitration
      by quercetin. The oxidation product was identified as 2-(3,4-dihydroxybenzoyl)
      2,4,6-trihydroxy-3(2H)-benzofuranone. This component could also be oxidized by
      salivary peroxidase and nitrogen dioxide radicals. The oxidation products were
      2,4,6-trihydroxyphenylglyoxylic and 3,4-dihydroxybenzoic acids. On the basis of
      the results, the significance of quercetin for inhibition of nitrogen dioxide
      formation and for scavenging of nitrogen dioxide radicals in the oral cavity is
      discussed.

PMID- 15853359
TI  - Development of a monoclonal antibody-based enzyme-linked immuosorbent assay for
      the beta-adrenergic agonist zilpaterol.
AB  - Zilpaterol is a beta-adrenergic agonist approved for use as a growth promoter in
      cattle in South Africa and Mexico but not in the European Union, United States,
      or Asia. Here, we report the development of a monoclonal antibody-based enzyme
      linked immunosorbent assay (ELISA) for zilpaterol. Mice immunized with zilpaterol
      butyrate-keyhole limpet hemocyanin were utilized for monoclonal antibody
      generation whereas zilpaterol-butyrate-bovine serum albumin was used as a coating
      antigen for ELISA. Thirteen clones were isolated, and after the initial
      sensitivity and isotyping experiments, three clones were selected for further
      ELISA optimization. Studies indicated that the optimum pH was near 7.4. Clone 3H5
      had the highest sensitivity to zilpaterol and some interaction with clenbuterol
      and terbutaline at high concentrations but not other N-alkyl [bamethane, (-)
      isoproterenol, (+)-isoproterenol, metaproterenol, or salbutamol] or N-arylalkyl
      (fenoterol, isoxsuprine, ractopamine, or salmeterol) beta-agonists tested.
      However, clone 3H5 was not functional at high salt concentrations, which
      precluded further development for urine analysis. Clone 2E10 showed increased
      sensitivity as salt concentrations were increased and did not cross-react with
      any of the structural analogues tested. However, its sensitivity to salt and
      urine concentration changes could cause high variability. Clone 7A8 showed good
      sensitivity and only a modest change with the salt concentration changes. Clone
      7A8 also demonstrated smaller changes in IC(50) and B(0) with increasing sheep
      urine or cattle urine concentrations as compared to clones 2E10 or 3H5 and, thus,
      was selected for further development. The IC(50) for all of the antibodies showed
      exponential increases with increasing organic solvents concentrations, making it
      desirable to minimize solvent levels. In conclusion, a sensitive, specific
      zilpaterol monoclonal antibody-based ELISA has been developed that can serve as a
      rapid screening assay.

PMID- 15853360
TI  - Detection of sugar adulterants in apple juice using fourier transform infrared
      spectroscopy and chemometrics.
AB  - Fourier transform infrared spectroscopy and attenuated total reflection sampling
      have been used to detect adulteration of single strength apple juice samples. The
      sample set comprised 224 authentic apple juices and 480 adulterated samples.
      Adulterants used included partially inverted cane syrup (PICS), beet sucrose
      (BS), high fructose corn syrup (HFCS), and a synthetic solution of fructose,
      glucose, and sucrose (FGS). Adulteration was carried out on individual apple
      juice samples at levels of 10, 20, 30, and 40% w/w. Spectral data were compressed
      by principal component analysis and analyzed using k-nearest neighbors and
      partial least squares regression techniques. Prediction results for the best
      classification models achieved an overall (authentic plus adulterated) correct
      classification rate of 96.5, 93.9, 92.2, and 82.4% for PICS, BS, HFCS, and FGS
      adulterants, respectively. This method shows promise as a rapid screening
      technique for the detection of a broad range of potential adulterants in apple
      juice.

PMID- 15853361
TI  - A comparison of the test tube and the dialysis tubing in vitro methods for
      estimating the bioavailability of phosphorus in feed ingredients for swine.
AB  - The validity of a simplified in vitro test tube (TT) method was compared with a
      more complicated dialysis tubing (DT) method to estimate the percentage of
      available phosphorus (P) in 41 plant origin and five animal origin feed
      ingredients for swine. The TT method using 1.0 or 0.25 g samples was compared
      with the DT method using 1.0 g samples at two pancreatic incubation times (2 vs 4
      h) in a 3 x 2 factorial arrangement of treatments. Each DT and TT method
      treatment was replicated three and six times, respectively. Both methods utilize
      three enzymatic digestions: (i) predigestion with endoxylanase and beta-glucanase
      for 1 h, (ii) pepsin digestion for 2 h, and (iii) pancreatin digestion for 2 or 4
      h. For the TT method, the entire procedure was conducted in a 50 mL conical
      centrifuge tube and replicated six times. For the DT method, the first two
      digestions were conducted in a 10 mL plastic syringe before the contents were
      quantitatively transferred into a segment of DT for the pancreatic digestion. The
      percentages of hydrolyzed P for plant origin ingredients measured by the DT
      method using 1.0 g samples and the TT method using 0.25 g samples were highly
      correlated (r = 0.94-0.97, P < 0.001) with each other and with published in vivo
      available P values for swine. Repeatabilities for these two methods ranged from
      99.64 to 99.86%. The TT method using 1.0 g samples, however, did not provide
      valid estimates of P availability for all ingredients. For animal origin
      ingredients, neither method was significantly correlated (r = 0.1-0.6, P >or =
      0.4) with published in vivo available P values. In conclusion, the accuracy and
      validity of the TT method using 0.25 g samples with a 2 h pancreatic digestion
      time was equal to or superior to the DT method using 1.0 g samples with a 4 h
      pancreatic digestion time for estimating P availability in plant origin feed
      ingredients.

PMID- 15853362
TI  - Optothermistor as a breakthrough in the quantification of lycopene content of
      thermally processed tomato-based foods: verification versus absorption
      spectrophotometry and high-performance liquid chromatography.
AB  - This study reports on the first use of the "optothermistor" as a novel, precise,
      fast, and low-cost detector of lycopene in a wide range of commercially available
      processed-tomato products. The quantitative performance of the new device was
      evaluated by comparing data obtained to that acquired by conventional methods,
      namely, absorption spectrophotometry and high-performance liquid chromatography
      (HPLC); the linear correlation was high (R = 0.98). The variation of data
      obtained with the optothermistor in a series of consecutive measurements
      performed with the same loading of the sample was better than 1%. However, the
      repeatability (RSD 0.5-9.0%, n = 3-5) achieved with the optothermistor by
      independent analyses (multiple loading) is comparable to that of HPLC and
      spectrophotometry. Results of the studies performed on the 19 products derived
      from tomatoes demonstrated that the optothermistor is suitable for selective,
      accurate, precise, and simple determination of lycopene (range = 7-75 mg/100 g of
      product weight) without the need for a sample pretreatment step. The estimated
      sensitivity of the present optothermistor is 2 mg of lycopene/100 g of product.

PMID- 15853363
TI  - Development and validation of an ultrasensitive chemiluminescent enzyme
      immunoassay for aflatoxin M1 in milk.
AB  - A fast and ultrasensitive chemiluminescent enzyme immunoassay for aflatoxin M(1)
      in milk samples has been developed and validated. The method is an indirect
      competitive type format involving the immobilization of an aflatoxin M(1)-bovine
      serum albumin conjugate on 384 well black polystyrene microtiter plates and the
      use of a secondary antibody labeled with horseradish peroxidase detected with a
      luminol-based substrate. Aflatoxin M(1) standard solutions were prepared in milk
      based buffer, and milk samples were analyzed without any cleanup procedure. The
      limit of quantification was 1 ppt, the coefficient of variation was below 9% for
      both intra- and interassay precision, and the recovery ranged from 96 to 122%.
      The method is specific, and other aflatoxins do not significantly cross-react
      with the antibody. Twenty-four milk samples were analyzed, and a good correlation
      was observed (y = 0.98x + 1.71, r(2) = 0.98, n = 24) when the data were compared
      with a reference high-performance liquid chromatography method with a fluorescent
      detector. The developed method is suitable for an accurate, sensitive, and high
      throughput screening of aflatoxin M(1) in milk samples with a reduction of costs
      and increased detectability, as compared with previously developed immunoassays.

PMID- 15853364
TI  - Development of a HPLC/tandem-MS method for the analysis of the larvicides
      methoprene, hydroprene, and kinoprene at trace levels using Diels-Alder
      derivatization.
AB  - The invasion and subsequent spread of the mosquito-borne West Nile virus in the
      United States has resulted in increased use of methoprene. With the increased
      need for sensitive detection and monitoring of methoprene in the environment, an
      analytical LC/ESI-MS/MS method has been developed for the analysis of methoprene
      and two analogues, kinoprene and hydroprene, in water. To improve the ionization
      efficiency of the nonpolar analytes, a derivatization step with the Cookson-type
      reagent 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) was used. Derivatization
      improved the limit of detection 100-fold. For tandem MS analyses, limits of
      detection in environmental water samples (S/N = 3) are about 6 pg/mL for
      methoprene and 20 pg/mL for kinoprene and hydroprene, resulting in limits of
      quantification (S/N = 10) of 20 pg/mL for methoprene and 60 pg/mL for hydroprene
      and kinoprene extracted from 10 mL of water. This method was applied to measure
      methoprene concentrations in water samples from a treated site.

PMID- 15853365
TI  - Antioxidants in raspberry: on-line analysis links antioxidant activity to a
      diversity of individual metabolites.
AB  - The presence of antioxidant compounds can be considered as a quality parameter
      for edible fruit. In this paper, we studied the antioxidant compounds in
      raspberry (Rubus idaeus) fruits by high-performance liquid chromatography (HPLC)
      coupled to an on-line postcolumn antioxidant detection system. Both developmental
      and genetic factors were assessed by comparing fruits from a single cultivar of
      different ripening stages and by comparing ripe fruits of 14 raspberry cultivars,
      respectively. The HPLC-separated antioxidant compounds were identified using HPLC
      photodiode array coupled to mass spectrometry (quadrupole time-of-flight tandem
      mass spectrometry), using a reference lock mass for determining accurate masses.
      The dominant antioxidants could be classified as anthocyanins, ellagitannins, and
      proanthocyanidin-like tannins. During fruit ripening, some anthocyanins were
      newly produced, while others, like cyanidin-3-glucoside, were already present
      early in fruit development. The level of tannins, both ellagitannins and
      proanthocyanidin-like tannins, was reduced strongly during fruit ripening. Among
      the 14 cultivars, major differences (>20-fold) were observed in the levels of
      pelagonidin type anthocyanins and some proanthocyanidin type tannins. The content
      of ellagitannins varied approximately 3-fold. The findings presented here suggest
      that the content of individual health-promoting compounds varies significantly in
      raspberry, due to both developmental and genetic factors. This information will
      assist in the future development and identification of raspberry lines with
      enhanced health-promoting properties.

PMID- 15853366
TI  - Sandwich immunoassays for the determination of peanut and hazelnut traces in
      foods.
AB  - People suffering from food allergies are dependent on accurate food labeling, as
      an avoidance diet is the only effective countermeasure. Even a small amount of
      allergenic protein can trigger severe reactions in highly sensitized patients.
      Therefore, sensitive and reliable tests are needed to detect potential cross
      contamination. In this paper two fast sandwich immunoassays are described for the
      determination of peanut (Arachis hypogaea) and hazelnut (Corylus avellana) traces
      in complex food matrices. Mouse monoclonal antibodies were used as capture
      antibodies, and labeled rabbit polyclonal antibodies were used as detection
      antibodies in both assays. The assay time was 30 min in total, and cross
      reactivities against a variety of fruits and seeds were found to be in the low
      10(-4)% (ppm) level or in some cases not detectable. The recoveries in all tested
      food matrices ranged from 86 to 127%, and the limits of detection were in the
      range of 0.2-1.2 mg/kg (ppm) in food for both peanut and hazelnut, respectively.

PMID- 15853367
TI  - Rapid screening of wood chemical component variations using transmittance near
      infrared spectroscopy.
AB  - A rapid transmittance near-infrared (NIR) spectroscopy method was developed to
      predict the variation in chemical composition of solid wood. The effect of sample
      preparation, sample quantity (single versus stacked multiple wood wafers), and
      NIR acquisition time on the quantification of alpha-cellulose and lignin content
      was investigated. Strong correlations were obtained between laboratory wet
      chemistry values and the NIR-predicted values. In addition to the experimental
      protocol and method development, improvements in calibration error associated
      with utilizing stacked multiple wood wafers as opposed to single wood wafers are
      also discussed.

PMID- 15853368
TI  - Interlaboratory transfer of a PCR multiplex method for simultaneous detection of
      four genetically modified maize lines: Bt11, MON810, T25, and GA21.
AB  - The number of cultured hectares and commercialized genetically modified organisms
      (GMOs) has increased exponentially in the past 9 years. Governments in many
      countries have established a policy of labeling all food and feed containing or
      produced by GMOs. Consequently, versatile, laboratory-transferable GMO detection
      methods are in increasing demand. Here, we describe a qualitative PCR-based
      multiplex method for simultaneous detection and identification of four
      genetically modified maize lines: Bt11, MON810, T25, and GA21. The described
      system is based on the use of five primers directed to specific sequences in
      these insertion events. Primers were used in a single optimized multiplex PCR
      reaction, and sequences of the amplified fragments are reported. The assay allows
      amplification of the MON810 event from the 35S promoter to the hsp intron
      yielding a 468 bp amplicon. Amplification of the Bt11 and T25 events from the 35S
      promoter to the PAT gene yielded two different amplicons of 280 and 177 bp,
      respectively, whereas amplification of the 5' flanking region of the GA21 gave
      rise to an amplicon of 72 bp. These fragments are clearly distinguishable in
      agarose gels and have been reproduced successfully in a different laboratory.
      Hence, the proposed method comprises a rapid, simple, reliable, and sensitive
      (down to 0.05%) PCR-based assay, suitable for detection of these four GM maize
      lines in a single reaction.

PMID- 15853369
TI  - Analysis of zearalenone in cereal and Swine feed samples using an automated flow
      through immunosensor.
AB  - The development of a sensitive flow-though immunosensor for the analysis of the
      mycotoxin zearalenone in cereal samples is described. The sensor was completely
      automated and was based on a direct competitive immunosorbent assay and
      fluorescence detection. The mycotoxin competes with a horseradish-peroxidase
      labeled derivative for the binding sites of a rabbit polyclonal antibody. Control
      pore glass covalently bound to Prot A was used for the oriented immobilization of
      the antibody-antigen immunocomplexes. The immunosensor shows an IC(50) value of
      0.087 ng mL(-1) (RSD = 2.8%, n = 6) and a dynamic range from 0.019 to 0.422 ng
      mL(-1). The limit of detection (90% of blank signal) of 0.007 ng mL(-1) (RSD =
      3.9%, n = 3) is lower than previously published methods. Corn, wheat, and swine
      feed samples have been analyzed with the device after extraction of the analyte
      using accelerated solvent extraction (ASE). The immunosensor has been validated
      using a corn certificate reference material and HPLC with fluorescence detection.

PMID- 15853370
TI  - New method of DNA isolation from two food additives suitable for authentication
      in polymerase chain reaction assays.
AB  - Locust bean gum and guar gum are galactomannans used as additives (E 410 and E
      412, respectively) in the food industry as stabilizing agents. Analytical
      discrimination between the two additives in gums and foods is now feasible by
      molecular techniques. However, only complex and time-consuming DNA isolation
      protocols are available to date. We have developed simple improved protocols to
      obtain enough DNA suitable for PCR amplification from a few milligrams of
      commercial E 410 and E 412 additives (containing more than 75% polysaccharides).
      The suspension of additives in water or 10 mM Tris-HCl, pH 8.5, efficiently
      recovers DNA suitable for authentication in PCR assays. However, the Tris method
      was much more efficient for the extraction of DNA from E 410 than for E 412
      additives. Conversely, the water method was the most suitable for detecting DNA
      extracted from E 412 or from E 410/E 412 mixtures. Combined with the use of the
      two specific ribosomal primer pairs previously designed, our methods are well
      suited for a fast and simple high-throughput sample treatment of commercial gums
      for molecular certification.

PMID- 15853371
TI  - Fish species identification using PCR-RFLP analysis and lab-on-a-chip capillary
      electrophoresis: application to detect white fish species in food products and an
      interlaboratory study.
AB  - Identification of 10 white fish species associated with U.K. food products was
      achieved using PCR-RFLP of the mitochondrial cytochrome b gene. Use of lab-on-a
      chip capillary electrophoresis for end-point analysis enabled accurate sizing of
      DNA fragments and identification of fish species at a level of 5% (w/w) in a fish
      admixture. One restriction enzyme, DdeI, allowed discrimination of eight species.
      When combined with NlaIII and HaeIII, specific profiles for all 10 species were
      generated. The method was applied to a range of products and subjected to an
      interlaboratory study carried out by five U.K. food control laboratories. One
      hundred percent correct identification of single species samples and six of nine
      admixture samples was achieved by all laboratories. The results indicated that
      fish species identification could be carried out using a database of PCR-RFLP
      profiles without the need for reference materials.

PMID- 15853372
TI  - Characterization of peppercorn, pepper oil, and pepper oleoresin by vibrational
      spectroscopy methods.
AB  - NIR-FT-Raman as well as ATR-IR and NIR spectroscopy in combination with efficient
      chemometric algorithms was applied for rapid determination of piperine in black
      and white ground pepper and green whole pepper berries as well as pepper
      oleoresins. Most of the well-resolved Raman signals detected in the spectra of
      pepper and the related oleoresins can be assigned to piperine, which is known to
      be the main pungent principle in these products. On the basis of the specific key
      bands of piperine, also selective Raman mappings were successfully performed to
      determine the in situ distribution of the alkaloid in the whole green berry and
      the dried peppercorn as well. It was found that piperine occurs more or less in
      the whole perisperm of the green fruit. Furthermore, the content and composition
      of the volatile fraction in various pepper samples were determined by applying
      the mentioned vibrational spectroscopy techniques. Whereas only NIRS measurements
      present sufficient reliability to predict the main essential oil substances
      directly in ground black and white pepper, all spectroscopy methods applied in
      this study can be used to analyze individual terpenoids in the hydrodistilled
      oil. It can be assumed that some of the new, efficient vibrational spectroscopy
      methods have the potential to replace the standard analysis procedures presently
      applied for the quality control of peppercorns, pepper extracts, and pepper oil.

PMID- 15853373
TI  - Development of an immunoassay-based lateral flow dipstick for the rapid detection
      of aflatoxin B1 in pig feed.
AB  - The aim of this work was to develop an immunoassay-based lateral flow dipstick
      for the rapid detection of aflatoxin B(1) in pig feed. The test consisted of
      three main components: conjugate pad, membrane, and absorbent pad. The membrane
      was coated with two capture reagents, that is, aflatoxin B(1)-bovine serum
      albumin conjugate and rabbit anti-mouse antibodies. The detector reagent
      consisted of colloidal gold particles coated with affinity-purified monoclonal
      anti-aflatoxin B(1) antibodies, which saturated the conjugate pad. A comparison
      of several extraction methods for the pig feed matrix is presented. A mixture of
      methanol/water (80:20, v/v) gave the best recoveries. After sample extraction and
      dilution, the dipstick was put in the sample solution at the conjugate pad side
      and developed for 10 min. Analyte present in the sample competed with the
      aflatoxin B(1) immobilized on the membrane for binding to the limited amount of
      antibodies in the detector reagent. Thus, the line color intensity of an
      aflatoxin B(1)-positive dipstick is visually distinguishable from that of an
      aflatoxin B(1)-negative sample. The visual detection limit for aflatoxin B(1) is
      5 microg/kg. The major advantages of this one-step striptest are that results can
      be obtained within 10 min and that all reagents are immobilized on the lateral
      flow dipstick.

PMID- 15853374
TI  - Angiotensin I converting enzyme inhibitory peptides from in vitro pepsin
      pancreatin digestion of soy protein.
AB  - Angiotensin I converting enzyme (ACE) inhibitory activity was determined in the
      soy protein isolate (SPI) digest produced by in vitro pepsin-pancreatin
      sequential digestion. The inhibitory activity was highest within the first 20 min
      of pepsin digestion and decreased upon subsequent digestion with pancreatin. An
      IC(50) value of 0.28 +/- 0.04 mg/mL was determined after 180 min of digestion,
      while no ACE inhibitory activity was measured for the undigested SPI at 0.73
      mg/mL. Chromatographic fractionation of the SPI digest resulted in IC(50) values
      of active fractions ranging from 0.13 +/- 0.03 to 0.93 +/- 0.08 mg/mL. Although
      many of the fractions showed ACE inhibition, peptides with lower molecular masses
      and higher hydrophobicities were most active. The findings show that many
      different peptides with ACE inhibitory activities were produced after in vitro
      pepsin-pancreatin digestion of SPI and lead to the speculation that physiological
      gastrointestinal digestion could also yield ACE inhibitory peptides from SPI.

PMID- 15853375
TI  - Major phytochemicals in apple cultivars: contribution to peroxyl radical trapping
      efficiency.
AB  - Forty-one samples of apples (peel plus pulp), obtained from eight cultivars, were
      examined for concentration of some important phytochemicals and for antioxidant
      activity expressed as peroxyl radical trapping efficiency. Five major
      polyphenolic groups plus ascorbate were identified and quantified by HPLC in the
      apple varieties. Oligomeric and polymeric proanthocyanidins were found to be
      about two-thirds of total polyphenols. The antioxidant efficiency of the apple
      extracts and of representative pure compounds for each group of phytochemicals
      was measured in a micellar system mimicking lipid peroxidation in human plasma.
      Although the amount of polyphenols measured by HPLC is similar to that measured
      by standard methods, the antioxidant efficiency calculated on the basis of the
      contribution of the pure compounds was lower than the antioxidant efficiency of
      the apple extracts. The higher efficiency of apples appears to be strictly
      related to the overwhelming presence of oligomeric proanthocyanidins.

PMID- 15853376
TI  - Lipid peroxidation by "free" iron ions and myoglobin as affected by dietary
      antioxidants in simulated gastric fluids.
AB  - Grilled red turkey muscle (Doner Kabab) is a real "fast food" containing
      approximately 200 microM hydroperoxides, homogenized in simulated gastric fluid
      and oxidized more rapidly at pH 3.0 than at pH 5.0, after 180 min, producing 1200
      and 600 microM hydroperoxides, respectively. The effects of "free" iron ions and
      metmyoglobin, two potential catalyzers of lipid peroxidation in muscle foods,
      were evaluated for linoleic acid peroxidation at pH 3.0 of simulated gastric
      fluid. The prooxidant effects of free iron ions on linoleic acid peroxidation in
      simulated gastric fluid was evaluated in the presence of ascorbic acid. At low
      concentrations of ascorbic acid, the effects were prooxidative, which was
      reversed at high concentrations. In the presence of metmyoglobin, ascorbic acid
      with or without free iron enhanced the antioxidative effect. Lipid peroxidation
      by an iron-ascorbic acid system was inhibited totally by 250-500 microM catechin
      at pH 3.0. The catechin antioxidant effect was determined also in the iron
      ascorbic acid system containing metmyoglobin. In this system, catechin totally
      inhibited lipid peroxidation at a concentration 20-fold lower than without
      metmyoglobin. The ability of catechin to inhibit lipid peroxidation was also
      determined at a low pH with beta-carotene as a sensitive target molecule for
      oxidation. The results show that a significant protection was achieved only with
      almost 100-fold higher antioxidant concentration. Polyphenols from different
      groups were determined for the antioxidant activity at pH 3.0. The results show a
      high antioxidant activity of polyphenols with orthodihydroxylated groups at the B
      ring, unsaturation, and the presence of a 4-oxo group in the heterocyclic ring,
      as demonstrated by quercetin.

PMID- 15853377
TI  - Lipid hydroperoxidase activity of myoglobin and phenolic antioxidants in
      simulated gastric fluid.
AB  - Our recent study demonstrated the potential of gastric fluid at pH 3.0 to
      accelerate lipid peroxidation and cooxidation of dietary constituents in the
      stomach medium. Metmyoglobin is known to catalyze the breakdown of lipid
      hydroperoxides to free radicals, a reaction that could enhance the propagation
      step and general lipid peroxidation. During this reaction, a part of the free
      radicals is autoreduced by metmyoglobin. At pH 3.0, metmyoglobin at low
      concentration was almost 7 x 10(4) times as effective as at pH 7.0 in enhancing
      the rate of lipid peroxidation. Our study demonstrated that metmyoglobin, at a
      low concentration (approximately 1:30), as compared with that of the
      hydroperoxides in the lipid system, worked prooxidatively increasing the amounts
      of linoleate hydroperoxides. However, at a high concentration (approximately
      1:3), metmyoglobin acted antioxidatively and decomposed hydroperoxides, whose
      concentrations then remained at zero for a long time. Catechin, a known
      polyphenol, supports the inversion of metmyoglobin catalysis, from prooxidation
      to antioxidation. The antioxidative activity of the couple metmyoglobin-catechin
      was better at pH 3.0 than at pH 7.0, indicating that this reaction is more
      dependent on metmyoglobin than on catechin. During this reaction, catechin or
      quercetin not only donates reducing equivalents to prevent lipid peroxidation but
      also prevents the destruction and polymerization of metmyoglobin. The results of
      this research highlighted the important and possible reactions of heme proteins
      and polyphenols as couple antioxidants, working as hydroperoxidases or as pseudo
      peroxidases. We hypothesize that the occurrence of these reactions in the stomach
      could have an important impact on our health and might help to better explain the
      health benefits of including foods rich in polyphenol antioxidants in the meal,
      especially when consuming red meat.

PMID- 15853378
TI  - Lipid peroxidation and coupled vitamin oxidation in simulated and human gastric
      fluid inhibited by dietary polyphenols: health implications.
AB  - The Western diet contains large quantities of oxidized lipids, because a large
      proportion of the food in the diet is consumed in a fried, heated, processed, or
      stored form. We investigated the reaction that could occur in the acidic pH of
      the stomach and accelerate the generation of lipid hydroperoxides and cooxidation
      of dietary vitamins. To estimate the oxygen content in the stomach after food
      consumption, oxygen released from masticated bread (20 g) into deoxygenated water
      (100 mL) was measured. Under these conditions, the oxygen concentration rose by
      250 microM and reached a full oxygen saturation. The present study demonstrated
      that heated red meat homogenized in human gastric fluid, at pH 3.0, generated
      hydroperoxides and malondialdehyde. The cross-reaction between free radicals
      produced during this reaction cooxidized vitamin E, beta-carotene, and vitamin C.
      Both lipid peroxidation and cooxidation of vitamin E and beta-carotene were
      inhibited at pH 3.0 by red wine polyphenols. Ascorbic acid (44 mg) at a
      concentration that represented the amount that could be ingested during a meal
      inhibited lipid peroxidation only slightly. Red wine polyphenols failed to
      prevent ascorbic acid oxidation significantly but, in conjunction with ascorbic
      acid, did inhibit lipid peroxidation. In the presence of catechin, a well-known
      polyphenol found in red wine, ascorbic acid at pH 3.0 works in a synergistic
      manner preventing lipid peroxidation and beta-carotene cooxidation. The present
      data may explain the major benefits to our health and the crucial role of
      consuming food products rich in dietary antioxidants such as fruits, vegetables,
      red wines, or green tea during the meal.

PMID- 15853380
TI  - A gamma-glutamyl peptide isolated from onion (Allium cepa L.) by bioassay-guided
      fractionation inhibits resorption activity of osteoclasts.
AB  - One gram of onion added to the food of rats inhibits significantly (p < 0.05)
      bone resorption as assessed by the urinary excretion of tritium released from
      bone of 9-week-old rats prelabeled with tritiated tetracycline from weeks 1 to 6.
      To isolate and identify the bone resorption inhibiting compound from onion, onion
      powder was extracted and the extract fractionated by column chromatography and
      medium-pressure liquid chromatography. A single active peak was finally obtained
      by semipreparative high-performance liquid chromatography. The biological
      activity of the various fractions was tested in vitro on the activity of
      osteoclasts to form resorption pits on a mineralized substrate. Medium,
      containing the various fractions or the pure compound, was added to osteoclasts
      of new-born rats settled on ivory slices. After 24 h of incubation, the tartrate
      resistant acid phosphatase positive multinucleated cells, that is, osteoclasts,
      were counted. Subsequently, the number of resorption pits was determined.
      Activity was calculated as the ratio of resorption pits/osteoclasts and was
      compared to a negative control, that is, medium containing 10% fetal bovine serum
      only and to calcitonin (10(-12) M) as a positive control. Finally, a single peak
      inhibited osteoclast activity significantly (p < 0.05). The structure of this
      compound was elucidated with high-performance liquid chromatography-electrospray
      ionization-mass spectrometry, time-of-flight electrospray ionization mass
      spectrometry, and nuclear magnetic resonance spectroscopy. The single peak was
      identified as gamma-L-glutamyl-trans-S-1-propenyl-L-cysteine sulfoxide (GPCS). It
      has a molecular mass of 306 Da and inhibits dose-dependently the resorption
      activity of osteoclasts, the minimal effective dose being approximately 2 mM. As
      no other peak displayed inhibitory activity, it likely is responsible for the
      effect of onion on bone resorption.

PMID- 15853379
TI  - Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor
      alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic
      hamsters.
AB  - Resveratrol, a stilbenoid antioxidant found in grapes, wine, peanuts and other
      berries, has been reported to have hypolipidemic properties. We investigated
      whether resveratrol and its three analogues (pterostilbene, piceatannol, and
      resveratrol trimethyl ether) would activate the peroxisome proliferator-activated
      receptor alpha (PPARalpha) isoform. This nuclear receptor is proposed to mediate
      the activity of lipid-lowering drugs such as the fibrates. The four stilbenes
      were evaluated at 1, 10, 100, and 300 microM along with ciprofibrate (positive
      control), for the activation of endogenous PPARalpha in H4IIEC3 cells. Cells were
      transfected with a peroxisome proliferator response element-AB (rat fatty acyl
      CoA beta-oxidase response element)-luciferase gene reporter construct.
      Pterostilbene demonstrated the highest induction of PPARalpha showing 8- and 14
      fold increases in luciferase activity at 100 and 300 microM, respectively,
      relative to the control. The maximal luciferase activity responses to
      pterostilbene were higher than those obtained with the hypolipidemic drug,
      ciprofibrate (33910 and 19460 relative luciferase units, respectively), at 100
      microM. Hypercholesterolemic hamsters fed with pterostilbene at 25 ppm of the
      diet showed 29% lower plasma low density lipoprotein (LDL) cholesterol, 7% higher
      plasma high density lipoprotein (HDL) cholesterol, and 14% lower plasma glucose
      as compared to the control group. The LDL/HDL ratio was also statistically
      significantly lower for pterostilbene, as compared to results for the control
      animals, at this diet concentration. Results from in vitro studies showed that
      pterostilbene acts as a PPARalpha agonist and may be a more effective PPARalpha
      agonist and hypolipidemic agent than resveratrol. In vivo studies demonstrate
      that pterostilbene possesses lipid and glucose lowering effects.

PMID- 15853381
TI  - Selective herbicide activity of 2,5-di(benzylamine)-p-benzoquinone against the
      monocot weed Echinochloa crusgalli. An in vivo analysis of photosynthesis and
      growth.
AB  - Six 2,5-diamino-p-benzoquinone derivatives previously characterized as
      photosystem I electron acceptors were tested for their postemergence herbicide
      activity. By induction kinetics of chlorophyll a fluorescence performed in vivo
      it was determined that 2,5-di(benzylamine)-p-benzoquinone diverted electrons at
      the reducing side of the chloroplast photosystem I. This derivative decreased the
      efficiency of photosystem II as evidenced by the decrease in the F(v)/F(m) change
      in Echinochloa crusgalli leaf disks. In addition, 2,5-di(benzylamine)-p
      benzoquinone was a CO(2) assimilation inhibitor to Rubisco: the A/C(i) curve
      analysis indicates that 2,5-di(benzylamine)-p-benzoquinone affected both the
      carboxylation reaction itself and the regeneration of RuBP. 2,5-di(benzylamine)-p
      benzoquinone did not exhibit any effect on the dicot plants Phaseolus vulgaris
      and Physalis ixocarpa or the monocot Zea mays. These species may have metabolized
      the herbicide to an inactive compound. Thus, 2,5-di(benzylamine)-p-benzoquinone
      was found to be a selective herbicide against the monocot weed E. crusgalli.

PMID- 15853382
TI  - Masked mycotoxins: determination of a deoxynivalenol glucoside in artificially
      and naturally contaminated wheat by liquid chromatography-tandem mass
      spectrometry.
AB  - Conjugated mycotoxins, in which the toxin is usually bound to a more polar
      substance like glucose, are referred to as masked mycotoxins, as these substances
      escape routine detection methods but can release their toxic precursors after
      hydrolysis. This is the first report on the natural occurrence of a glucoside of
      deoxynivalenol (DON) in Fusarium-infected wheat and maize. To obtain appropriate
      standards, we chemically synthesized deoxynivalenol-3-beta-D-glucopyranoside (DON
      3-glucoside) and deoxynivalenol-15-beta-D-glucopyranoside (DON-15-glucoside). The
      synthesis products were characterized by liquid chromatography-tandem mass
      spectrometry. The DON-glucosides showed different collision-induced dissociation
      (CID) fragmentation behaviors and could therefore be distinguished. Wheat plants
      were either treated with DON (n = 52) or with Fusarium spp. (n = 4) at anthesis,
      and after harvest, wheat ears were analyzed for DON and DON-glucosides. All 56
      treated wheat samples contained DON and a DON-glucoside with the same retention
      time, molecular mass, and CID fragmentation behavior as the synthetic DON-3
      glucoside. Moreover, the DON-glucoside was also found in two out of three
      analyzed naturally DON-contaminated maize and in five out of five naturally
      contaminated wheat samples, in a range from 4 to 12% of the DON concentration. To
      further confirm the identity of the DON-glucoside, the compound was isolated from
      wheat extracts and characterized as DON-3-glucoside with NMR. The results of this
      study indicate the importance to consider both DON and DON-3-glucoside with
      regard to food and feed safety.

PMID- 15853383
TI  - Identification of casein phosphopeptides released after simulated digestion of
      milk-based infant formulas.
AB  - Adapted, follow-up, probiotic follow-up, toddler, and probiotic toddler infant
      formulas were subjected to an in vitro enzymatic procedure simulating
      physiological digestion. The formation and identification of casein
      phosphopeptides (CPPs) in the milk-based infant formulas were studied using
      reversed phase high-performance liquid chromatography coupled on line to an ion
      trap mass spectrometer. Most CPPs formed contained the cluster sequence SpSpSpEE,
      a mineral binding site. Phosphopeptide alpha(s2)-CN(1-19)4P was present in all
      formulas analyzed. Probiotic formulas released CPPs not detected in nonprobiotic
      formulas and probably formed by bifidobacteria action. These observations suggest
      that physiological digestion of these products promotes the formation of
      bioactive peptides with mineral carrier properties in the gastrointestinal tract,
      which resist further proteolysis.

PMID- 15853384
TI  - Thermo-FTIR spectroscopic study of the siderophore ferrioxamine B: spectral
      analysis and stereochemical implications of iron chelation, pH, and temperature.
AB  - FTIR spectra of the microbial siderophore, ferrioxamine B, and its nonchelated
      form (iron free; desferrioxamine B) were studied to facilitate in-depth
      investigation on the undisrupted structure of the siderophore and its
      interactions with the environment. Effects of iron chelation as well as those of
      various levels of pH and temperature on the stereochemical structure of the free
      ligand and the ferric complex were examined. The presence of a number of
      functional groups in these compounds and the mutual interaction between them
      resulted in significant shifts and overlapping of their characteristic absorption
      bands. Thermal and pH treatments combined with a comprehensive use of curve
      fitting analysis facilitated bands resolution. Absorption bands of all functional
      groups were identified. The results imply that the compact and rigid structure of
      the ferric complex (ferrioxamine B) is sustained by intense and specific
      intramolecular hydrogen bonds. Dehydration was the main process observed at low
      temperature (25-60 degrees C). At 105 degrees C the free ligand form
      (desferrioxamine B) had already begun to decompose, whereas ferrioxamine B
      exhibited stability. The thermal destruction became acute at the 170 degrees C
      treatment for both molecules. The secondary amide groups and the hydroxamate
      groups, which comprise the binding site for the Fe atom in the complex, were
      found to be the most sensitive to the thermal degradation. Significant pH effects
      were observed only for desferrioxamine B samples at pH 9, accompanied by partial
      decomposition, similar to that observed at 105 degrees C. Deprotonation of
      desferrioxamine B was found to begin with the deprotonation of the NH(3+) group.
      Characteristics of the rigid conformational structure of the ferric complex and
      the state of the NH(3+) group, both assumed to play an important role in the
      recognition and uptake of the siderophore by membranal receptors, were elaborated
      by means of FTIR and are discussed in detail.

PMID- 15853385
TI  - Properties of zein films coated with drying oils.
AB  - Zein films prepared by resin were coated with either flax oil or tung oil and
      cured by UV- or gamma-radiation. Coated zein films were then evaluated for
      tensile and water barrier properties. Film microstructure was examined by
      transmitted light microscope. Tensile strength, elongation, and toughness of oil
      coated samples increased substantially with respect to uncoated films. Flax oil
      coated samples showed an increase in elongation of 300%. It was suggested that
      oil coatings fill in pinholes and cracks existing in zein films, affecting their
      mechanical properties. Water vapor permeability also decreased statistically for
      coated film (except for tung oil coated-UV treated films), suggesting water vapor
      transfer was controlled by film hydrophobicity and microstructure. Moreover, the
      liquid water transmission rate of coated films was at least 10 times slower than
      for control films. Examination of film microstructure revealed that flax oil
      coatings had uniform coverage and smooth finish, which explained their high
      elongation, low water vapor permeability. Tung oil coatings cured under UV light
      showed patterns of intertwined dark and light regions, which may be caused by
      cross-linking and drying at different times. The oriented structures were found
      when tung oil coatings were cured by gamma-radiation.

PMID- 15853386
TI  - Biotransformation and impact of ferulic acid on phenylpropanoid and capsaicin
      levels in Capsicum annuum L. cv. P1482 cell suspension cultures.
AB  - Cell suspension cultures of Capsicum annuum L. cv. P1482 were fed with exogenous
      ferulic acid to monitor their biotransformation abilities. A portion of the
      ferulic acid was biotransformed into vanillin, a major natural flavor, and
      capsaicin, a principle secondary metabolite characteristic of Capsicum species.
      The cellular vanillin concentrations were relatively higher than capsaicin levels
      and were maximal (2 mg/g DW) 4 days after 0.6 mM ferulic acid feeding. Maximal
      vanillin levels in the culture medium were 10 mg/L at 4 and 3 days after feeding
      with 1.25 and 2.5 mM ferulic acid, respectively. With regard to capsaicin levels,
      the cellular levels were slightly decreased by ferulic acid feeding, whereas the
      levels in the culture medium were increased. Ferulic acid feeding not only
      enhanced vanillin and capsaicin production but also increased the concentrations
      of other phenylpropanoid metabolites.

PMID- 15853387
TI  - 14-3-3 protein down-regulates key enzyme activities of nitrate and carbohydrate
      metabolism in potato plants.
AB  - The 14-3-3 protein is one of the best candidates for coordinating all plant
      metabolic pathways. To verify this suggestion transgenic potato plants with
      repression of one (J4 and J5 plants), two (G1 plants), and six (G3 plants)
      constitutive 14-3-3 protein isoforms as well as plants overexpressing the 14-3-3
      protein were studied. Reduction in the 14-3-3 protein level in the J4 and J5
      transformants, the G1 transformants, and the G3 transformants was close to 29,
      41.5, 38, and 55%, respectively. In the case of the 14-3-3 overexpressing plants
      (J2), a 30% increase in protein content was detected. Changes in nitrate
      reductase (NR), sucrose phosphate synthase (SPS), and starch synthase (SS)
      activities in the transgenic plants perfectly reflect the overall 14-3-3 protein
      level. The highest increase in enzyme activities was observed for the G3 plants
      and the lowest for the J4 transformants. The same was detected for the measured
      metabolites. The highest increase in the protein, starch, and sucrose levels was
      detected in the tubers from the G3 transgenic plants. Because there was almost no
      change in the isoform ratio in the transgenic plants when compared to the
      control, it is suggested that it is the overall content of the 14-3-3 protein,
      rather than the content of particular isoforms, which plays a crucial role in the
      regulation of enzyme activities and thus in metabolite synthesis. The properties
      of the 14-3-3 overexpressing plants are very similar to those of the control
      ones, suggesting that the protein is in excess in the nontransformants and a
      further increase in its content is not recognized by cell metabolism. A
      considerable influence of the 14-3-3 protein level on potato plant metabolism was
      demonstrated. This effect was observed in key metabolic enzyme activities and
      metabolite content as well. A high variability between mean values, representing
      individual transgenes, with respect to nitrate reductase, sucrose phosphate
      synthase, and starch synthase activities in the examined genotypes was noted.
      These changes were closely correlated with metabolite levels, among them protein,
      starch, reducing sugars, and sucrose. The results obtained for the five types of
      transgenic potato plants in comparison with the control were statistically
      assessed using discriminate function and cluster analyses.

PMID- 15853388
TI  - Transgenic rice containing human CYP2B6 detoxifies various classes of herbicides.
AB  - The human gene for CYP2B6, a cytochrome P450 monooxygenase that inactivates
      xenobiotic chemicals, was introduced into Oryza sativa cv. Nipponbare by
      Agrobacterium-mediated transformation. At germination, R(1) seeds of transgenic
      rice plants expressing CYP2B6 (CYP2B6 rice) showed a high tolerance to 5 microM
      metolachlor, a preemergence herbicide that is degraded by CYP2B6. Thin-layer
      chromatography after culture with (14)C-labeled metolachlor revealed that the
      amounts of residual metolachlor decreased in plant tissues and the medium of
      CYP2B6 rice faster than those of untransformed Nipponbare. CYP2B6 rice plants
      were able to grow in the presence of 13 out of 17 herbicides: five
      chloroacetamides and mefenacet, pyributicarb, amiprofos-methyl, trifluralin,
      pendimethalin, norflurazon, and chlorotoluron. These herbicides differ in their
      modes of action and chemical structures. Transgenic rice expressing a xenobiotic
      degrading human CYP2B6, which has broad substrate specificity, should be good not
      only for developing herbicide tolerant rice but also for reducing the
      environmental impact of agrochemicals.

PMID- 15853389
TI  - Quantitative structure-activity relationship analysis as a tool to evaluate the
      mode of action of chemical hybridizing agents for wheat (Triticum aestivum L.).
AB  - Augmentation of wheat production calls for introduction of wheat hybrids in
      cultivation. In the absence of viable alternative technology of hybrid wheat
      development, chemical induction of male sterility mediated technology based on
      chemical hybridizing agents (CHAs) holds a great potential. The QSAR method was
      applied to two families of CHAs in the N-acylanilines and pyridone class of
      chemistry. The models for each CHA family gave good correlation between the
      variations in log percent of male sterility and the steric-electrostatic
      properties of the sets. QSAR analysis has revealed a direct relationship of the
      Swain-Lupton constant F(p) and molecular mass but an inverse relationship of MR,
      ES, and Swain-Lupton resonance constant R in influencing the bioactivity in the N
      acylanilines. QSAR analysis of four parent families consisting of two training
      sets each of pyrid-2-ones and prid-4-ones revealed the positive contributions of
      field effect exemplified by the Swain-Lupton field constant (F) and the negative
      contributions of the molar refractivity (MR) of aromatic substituents in all but
      one training set. The QSAR models also indicated that increased steric bulk at
      the 4-position on the phenyl ring is associated with enhanced activity. These
      leads will be useful in explaining the CHA binding fit in the macromolecular
      receptor site.

PMID- 15853390
TI  - Heat-induced soy-whey proteins interactions: formation of soluble and insoluble
      protein complexes.
AB  - The aggregation behavior during heating of a solution containing soy protein and
      whey protein isolate (WPI) was studied using rheology, confocal microscopy, gel
      filtration, and electrophoresis. Soy/WPI mixtures formed gels at 6% total protein
      concentration with a high elastic modulus (G') and no apparent phase separation.
      The ratio of soy to WPI was fundamental in determining the type of network
      formed. Systems containing a high soy to WPI ratio (>70% soy protein) showed a
      different evolution of the elastic modulus during heat treatment, with two
      apparent stages of network development. Whey proteins formed disulfide bridges
      with soy proteins during heating, and at low ratios of soy/WPI, the aggregates
      seemed to be predominantly formed by 7S, the basic subunits of 11S and beta
      lactoglobulin. Size exclusion chromatography indicated the presence of high
      molecular weight soluble complexes in mixtures containing high soy/WPI ratios.
      Results presented are the first evidence of interactions between soy proteins and
      whey proteins and show the potential for the creation of a new group of
      functional ingredients.

PMID- 15853391
TI  - Formation of decarboxylated betacyanins in heated purified betacyanin fractions
      from red beet root (Beta vulgaris L.) monitored by LC-MS/MS.
AB  - Mixtures of mono-, bi-, and tridecarboxylated betacyanins together with their
      corresponding neobetacyanins obtained from Beta vulgaris L. root juice as heating
      degradation products of betacyanins were identified by high-performance liquid
      chromatography with tandem mass spectrometry (LC-MS/MS) and diode-array (LC-DAD)
      detection. Two monodecarboxy-betacyanin pairs of diastereomers were detected
      after the decarboxylation in ethanolic and aqueous solutions. Generation of 17
      decarboxy-betacyanins and 2-decarboxy-betacyanins was suggested, the latter so
      far never having been attributed to betacyanin thermal degradation products.
      Other main products of decarboxylation were 2,17-bidecarboxybetanin, its isoform,
      and 14,15-dehydrogenated (neobetacyanin) derivatives of all the decarboxylated
      betacyanins. The results of this research are crucial in determining betacyanin
      degradation mechanisms in juices or extracts of B. vulgaris L. roots and other
      products containing these pigments.

PMID- 15853392
TI  - pH of solution greatly affects sorption of ionizable compounds into low-density
      polyethylene film.
AB  - Sorption of ionizable compounds of pyridines and aromatic carboxylic acids into
      low-density polyethylene (LDPE) film was investigated as a function of pH ranging
      from 4 to 7. The sorptions for pyridines were increased with increasing pH.
      Within the range examined, pH 7 was observed to promote the highest degree of
      sorption. When the pH increased by one unit from 6 to 7, the sorptions for 2
      propylpyridine and 2,4,6-trimethylpyridine were both increased approximately 3.8
      and 10.5 times, respectively. At pH 4, the sorption for the pyridines entirely
      disappeared. In contrast, the sorptions for aromatic carboxylic acids increased
      with decreasing pH. Within the range examined, pH 4 was observed to promote the
      highest degree of sorption. The magnitude of sorption for pyridines and
      carboxylic acids apparently depended on the affinity (delta(c)) of these
      compounds for LDPE film. Another factor affecting the sorption at various pHs was
      the pK(a) of these compounds; the sorption greatly decreased with the ionization
      degree of these compounds. To elucidate the phenomena, the following
      thermodynamic sorption equation was applied: S = S(0)gamma exp[V(v){(delta(w) -
      delta(v))(2) - delta(c)(2))/RT}. The plots of ln S for pyridines vs the term of
      the equation gave an insufficient relationship (r = 0.519). In contrast, taking
      into account the ratio (chi(i)()) of concentration of un-ionized compound to
      total concentration, the improvement for the equation was made: S' = S/chi(i)() =
      S(0)gamma exp[V(v){(delta(w) - delta(v))(2) - delta(c)(2))/RT}. The plots of ln
      S' vs the term of the equation gave a better relationship (r = 0.884).
      Furthermore, the equation was also applicable for the sorption behavior of
      carboxylic acids into LDPE (r = 0.769).

PMID- 15853393
TI  - Rapid measurement and evaluation of the effect of drying conditions on
      harpagoside content in Harpagophytum procumbens (devil's claw) root.
AB  - The effect of drying conditions on harpagoside (HS) retention, as well as the use
      of near-infrared spectroscopy (NIRS) for rapid quantification of the iridoids,
      HS, and 8-rho-coumaroyl harpagide (8rhoCHG) and moisture, in dried Harpagophytum
      procumbens (devil's claw) root was investigated. HS retention was significantly
      (P < 0.05) lower in sun-dried samples as compared to tunnel-dried (60 degrees C,
      30% relative humidity) and freeze-dried samples. The best retention of HS was
      obtained at 50 degrees C when evaluating tunnel drying at dry bulb temperatures
      of 40, 50, and 60 degrees C and 30% relative humidity. NIRS can effectively
      predict moisture content with a standard error of prediction (SEP) and
      correlation coefficient (r) of 0.24% and 0.99, respectively. The HS and 8rhoCHG
      NIRS calibration models established for both iridoid glucosides can be used for
      screening purposes to get a semiquantitative classification of devil's claw roots
      (for HS: SEP = 0.236%, r = 0.64; for 8rhoCHG: SEP = 0.048%, r = 0.73).

PMID- 15853394
TI  - Formation pathways of ethyl esters of branched short-chain fatty acids during
      wine aging.
AB  - The particular behavior during wine aging of fermentative branched fatty acid
      ethyl esters, related to yeast nitrogen metabolism, compared that of their
      straight-chain analogues, related to yeast lipid metabolism, was first checked in
      1-5 year aged Muscadet wines. Quantitative SIDA measurements showed that the
      levels of the former increased, whereas those of the latter decreased. Then,
      three hypothetical pathways suggested in the literature to explain these
      variations of branched esters were investigated. Two Muscadet and Sylvaner wines
      were spiked with levels of deuterated isobutanoic acid and its ethyl ester,
      similar to those of their natural analogues, then they were submitted to model
      aging. Quantitative SIDA measurements on the formation of these natural and
      labeled ethyl esters from the corresponding acids revealed that the behavior of
      the natural and labeled compounds were similar. The acid levels were much higher
      than the ester levels in the initial young wine, and a significant upward trend
      of their esterification ratios to those of the acid-ester equilibrium was
      observed with aging. Thus, this equilibrium proved to be the most effective in
      generating the branched fatty acid ethyl esters during wine aging. In contrast,
      the formation of these acids by Strecker-type degradation of wine amino acids in
      the conditions of the model aging or by hydrolysis of their glycoconjugates
      proved to be ineffective.

PMID- 15853395
TI  - Sodium carbonate treatment induces scoparone accumulation, structural changes,
      and alkalinization in the albedo of wounded citrus fruits.
AB  - Following sodium carbonate treatment, accumulation of scoparone (6,7
      dimethoxycoumarin) but not scopoletin (6-methoxy-7-hydroxycoumarin) was found in
      the albedo of wounded fruit from different Citrus sp. and cultivars. Treating
      wounded mandarin fruit cv. Fairchild with 5% Na(2)CO(3) (SC) lead to a scoparone
      accumulation in the albedo of 310, 361, and 382 microg g(-1) fresh weight after
      7, 10, and 15 days, respectively. Scoparone accumulation was associated with a
      decrease in decay severity. When oranges cv. Biondo comune wounded and treated
      with 5% SC were inoculated with Penicillium digitatum or Penicillium italicum
      conidia 3 days posttreatment, the decay percentage as compared to untreated
      wounds was reduced by 97.2 and 93.9%, respectively. Observations by scanning
      electron microscopy of wounded Citrus fruits treated at 20 degrees C with 2, 3,
      4, or 5% (w/v) solutions of sodium carbonate showed structural modifications to
      the albedo as well as damage to 24-48 h old mycelia of P. digitatum, the cause of
      citrus green mold. Modifications were more evident in orange, lemon, and
      grapefruit as compared to mandarin fruit. The efficacy of the treatment was
      strictly related to the SC interaction with the albedo tissue that, in addition
      to structural changes, significantly increased tissue pH, affecting P. digitatum
      pathogenicity. The SC remaining as a film on unwounded flavedo had no effect in
      preventing contact infection by the Penicillia.

PMID- 15853396
TI  - Effect of ultrahigh-temperature continuous ohmic heating treatment on fresh
      orange juice.
AB  - The scope of this study is the effect of ohmic heating thermal treatment on
      liquid fruit juice made of oranges. Effects of ohmic heating on the quality of
      orange juice were examined and compared to those of heat pasteurization at 90
      degrees C for 50 s. Orange juice was treated at temperatures of 90, 120, and 150
      degrees C for 1.13, 0.85, and 0.68 s in an ohmic heating system. Microbial counts
      showed complete inactivation of bacteria, yeast, and mold during ohmic and
      conventional treatments. The ohmic heating treatment reduced pectin esterase
      activity by 98%. The reduction in vitamin C was 15%. Ohmic-heated orange juice
      maintained higher amounts of the five representative flavor compounds than did
      heat-pasteurized juice. Sensory evaluation tests showed no difference between
      fresh and ohmic-heated orange juice. Thus, high-temperature ohmic-heating
      treatment can be effectively used to pasteurize fresh orange juice with minimal
      sensory deterioration.

PMID- 15853397
TI  - Isolation, characterization, and antioxidant activity of E- and Z-p-coumaryl
      fatty acid esters from cv. Annurca apple fruits.
AB  - A total of 12 fatty acid esters of Z- and E-p-coumaryl alcohol were isolated from
      cv. Annurca apple fruit and characterized. This apple variety is widely
      cultivated in the south of Italy, and the fruits typically undergoe a reddening
      treatment after harvest. Structures of the p-coumaryl esters were elucidated by
      GC-MS and (1)H and (13)C NMR after purification of individual compounds by HPLC.
      It was found that the esters are localized in the fruit peel. During reddening of
      the fruit, there was a substantial increase in the amount of esters and
      particularly in molecular species with unsaturated fatty acids. The individual
      compounds were tested for antioxidant activity, and over half were shown to be at
      least as effective as alpha-tocopherol.

PMID- 15853398
TI  - Application of Hansch's model to guaianolide ester derivatives: a quantitative
      structure-activity relationship study.
AB  - A quantitative structure-activity study to evaluate the effect of
      lipophilia/aqueous solubility on etiolated wheat coleoptiles elongation has been
      carried out with 34 guaianolides having different numbers of hydroxyl groups and
      ester side chains of variable length and structure: linear, branched, aromatic,
      and unsaturated. Compounds have been tested in a range of concentrations between
      10 and 1000 microM. Data show a strong influence of lipophilia, expressed as logP
      values. Specially, data from alkylic side chain ester derivatives adjust to the
      mathematical model based on Hansch's transport theory; hence, a quantitative
      structure-activity relationships (QSAR) correlation with a high degree of
      reliance is provided. Moreover, all active compounds fit the Lipinski's rule of
      five. Also, the presence of additional hydroxyl groups and their derivatives in
      the basic skeleton does not affect the mode of action but greatly influences the
      activity, as they modify the transport through membranes and aqueous phases.
      Finally, a second hydroxyl group enhances differences of activity between alkylic
      side chain derivatives by increasing differences in van der Waals interactions.

PMID- 15853399
TI  - Controlled release of the herbicide norflurazon into water from ethylcellulose
      formulations.
AB  - The herbicide norflurazon was encapsulated in ethylcellulose (EC(40))
      microspheres by the solvent evaporation technique to obtain controlled release
      formulations. The kinetics of release of the active ingredient into the aqueous
      solution from different preparations was determined. It was found that the
      percentage release of the incorporated herbicide was a function of the
      composition and formation conditions of the formulations (amount of emulsifying
      agent, EC(40)/herbicide ratio, stirring speed, and percentage of pore-forming
      agent). The percentage of the herbicide release was related to the properties of
      the different microspheres obtained, such as particle size distribution,
      herbicide loading, or surface morphology. The release percentage depended
      inversely on the particle size of the microspheres and directly on the content of
      active ingredient and emulsifying and pore-forming agents. An empirical equation
      was used to fit the herbicide release data, indicating that the release of
      norflurazon from the various formulations is controlled by a diffusion mechanism.
      The time taken for 50% of the active ingredient to be released into water (T(50))
      was calculated, showing a wide variation among the different preparations (0.95
      16.4 days).

PMID- 15853400
TI  - Sorption of 2,4,6-trichlorophenol in model humic acid-clay systems.
AB  - Humic acids and clays are important soil components that influence the sorption
      and desorption of organic contaminants; however, it is unclear how humic acids
      influence the sorption of organic contaminants onto clays and their subsequent
      desorption. Sorption and desorption of 2,4,6-trichlorophenol (2,4,6-TCP) by and
      from humic acid-modified K(+)- and Ca(2+)-montmorillonite and -illite were
      compared with unmodified clays using batch equilibration methods. Commercial
      humic acid and the humic acid extracted from forest soil were employed in this
      experiment. The adsorbed amount of 2,4,6-TCP by commercial humic acid was almost
      twice as large as that adsorbed by the extracted soil humic acid. More 2,4,6-TCP
      was sorbed onto K(+)- and Ca(2+)-illite than onto K(+)- and Ca(2+)
      montmorillonite. K(+) clays were more effective in adsorbing 2,4,6-TCP than
      Ca(2+) clays. Sorption of 2,4,6-TCP on humic acid-modified Ca(2+)- and K(+)
      montmorillonite and -illite increased as compared with unmodified clays. The
      sorption nonlinearity of 2,4,6-TCP on humic acid-modified Ca(2+)- and K(+)-illite
      increased remarkably as compared with the unmodified clays. The sorption
      nonlinearity of 2,4,6-TCP on humic acid-modified Ca(2+)- and K(+)-montmorillonite
      increased slightly in contrast to unmodified montmorillonites. By comparing
      sorption and desorption results, we observed hysteresis for all sorbents
      including humic acids, clays, and humic acid-modified clays. Sorption
      nonlinearity and hysteresis were dependent on the structure of humic acids.
      Higher aromaticity of humic acids resulted in greater sorption nonlinearity and
      desorption hysteresis. In addition, sorption capacity (K(f)') was positively
      correlated with the humic acid content of the sorbents. These results show that
      modification of humic acids on clays can not only increase the adsorption ability
      of clays but also affect the sorption nonlinearity of 2,4,6-TCP, and the
      desorption hysteresis was probably due to the structural characteristics of humic
      acids.

PMID- 15853401
TI  - Arsenic transport and transformation associated with MSMA application on a golf
      course green.
AB  - The impact of extensively used arsenic-containing herbicides on groundwater
      beneath golf courses has become a topic of interest. Although currently used
      organoarsenicals are less toxic, their application into the environment may
      produce the more toxic inorganic arsenicals. The objective of this work was to
      understand the behavior of arsenic species in percolate water from monosodium
      methanearsonate (MSMA) applied golf course greens, as well as to determine the
      influences of root-zone media for United State Golf Association (USGA) putting
      green construction on arsenic retention and species conversion. The field test
      was established at the Fort Lauderdale Research and Education Center (FLREC),
      University of Florida. Percolate water was collected after MSMA application for
      speciation and total arsenic analyses. The results showed that the substrate
      composition significantly influenced arsenic mobility and arsenic species
      transformation in the percolate water. In comparison to uncoated sands (S) and
      uncoated sands and peat (S + P), naturally coated sands and peat (NS + P) showed
      a higher capacity of preventing arsenic from leaching into percolate water,
      implying that the coatings of sands with clay reduce arsenic leaching. Arsenic
      species transformation occurred in soil, resulting in co-occurrence of four
      arsenic species, arsenite (As(III)), arsenate (As(V)), monomethylarsonic acid
      (MMA), and dimethylarsinic acid (DMA) in percolate water. The results indicated
      that substrate composition can significantly affect both arsenic retention in
      soil and arsenic speciation in percolate water. The clay coatings on the soil
      particles and the addition of peat in the soil changed the arsenic
      bioavailability, which in turn controlled the microorganism-mediated arsenic
      transformation. To better explain and understand arsenic transformation and
      transport after applying MSMA in golf green, a conceptual model was proposed.

PMID- 15853402
TI  - Impact of growing environment on chickasaw blackberry (Rubus L.) aroma evaluated
      by gas chromatography olfactometry dilution analysis.
AB  - The aroma extract of Chickasaw blackberry (Rubus L.) was separated with silica
      gel normal phase chromatography into six fractions. Gas chromatography
      olfactometry (GCO) was performed on each fraction to identify aroma active
      compounds. Aroma extraction dilution analysis (AEDA) was employed to characterize
      the aroma profile of Chickasaw blackberries from two growing regions of the
      United States: Oregon and Arkansas. Comparative AEDA analysis showed that the
      berries grown in the two regions had similar aroma compositions; however, those
      odorants had various aroma impacts in each region. The compounds with high flavor
      dilution factors in Oregon's Chickasaw were ethyl butanoate, linalool, methional,
      trans,cis-2,6-nonadienal, cis-1,5-octadien-3-one, and 2,5-dimethyl-4-hydroxy
      3(2H)-furanone, whereas in the Chickasaw grown in Arkansas, they were ethyl
      butanoate, linalool, methional, ethyl 2-methylbutanoate, beta-damascenone, and
      geraniol.

PMID- 15853403
TI  - Model studies on retention of added volatiles during breadcrumb production.
AB  - Breadcrumb samples were prepared with a range of volatile compounds at known
      concentrations. The retention of these volatiles was assessed via solvent
      extraction and quantification by gas chromatography-mass spectrometry. Volatile
      loss during processing was shown to be substantial and dependent upon the
      compound's vapor pressure. The influence of initial concentration levels on the
      retention of volatiles was linear within the bounds of the experimental
      concentrations (0-300 mg/kg). Comparison of volatile concentration at various
      stages throughout the production process (by headspace analysis) showed that the
      greatest losses occurred during the processing stages that involved heat, namely,
      microwave heating and drying. The production of samples by freeze drying showed
      an increased average retention of 17% as compared to fluidized bed drying and
      flat bed drying, which showed the highest volatile losses.

PMID- 15853404
TI  - Effect of xanthan on flavor release from thickened viscous food model systems.
AB  - The influence of xanthan concentration (0, 0.02, 0.1, 0.4, and 0.8% w/w) and bulk
      viscosity on the release of 20 aroma compounds of different chemical classes (5
      aldehydes, 4 esters, 5 ketones, 3 alcohols, and 3 terpenes) was evaluated in
      xanthan-thickened food model systems having different viscosities. Interactions
      between flavor compounds and xanthan were assessed by measuring air-liquid
      partition coefficients, K, of aroma compounds in pure water and in the xanthan
      solutions by static headspace gas chromatography. Mass transfer of aroma
      compounds was estimated by dynamic headspace gas chromatography. Notably,
      limonene and some of the esters and aldehydes exhibited decreased K values in the
      presence of xanthan, indicating that the release of these volatile aroma
      compounds was reduced due to interaction with the xanthan matrix. The degree of
      interaction depended on the physicochemical characteristics of the aroma
      compounds. A similar tendency was observed at nonequilibrium with the decreases
      in release rates being most pronounced for limonene, followed by the esters and
      aldehydes, with no effect for ketones and an apparent "salting out" effect for
      alcohols. The reduction in flavor release by xanthan was thus dependent on the
      physicochemical properties of the aroma compounds and was apparently a result of
      the aroma-xanthan interactions and not influenced by the viscosity of the system
      itself.

PMID- 15853405
TI  - Quantitative analysis, occurrence, and stability of (E)-1-(2,3,6
      Trimethylphenyl)buta-1,3-diene in wine.
AB  - A stable isotope dilution assay has been developed for quantification of (E)-1
      (2,3,6-trimethylphenyl)buta-1,3-diene (4) in wine using a [(2)H(6)]-analogue.
      Using this method, 4 was found in 96 out of 97 white wines, but in none of 12 red
      wines analyzed. 4 was found to be most prevalent in Semillon wines, followed by
      Chardonnay, with Riesling showing the least amount of 4 among these three
      varieties. 4, like 1,1,6-trimethyldihydronaphthalene (TDN, 3), appears to be
      formed during the aging process. 4 was found to be unstable in model wine, and in
      both white and red wine, with the order of stability being model > white > red.
      In a PVPP-stripped red wine, the rate of degradation of 4 was substantially
      lessened, with the final concentrations very close to those observed in model
      wine. When treated with either grape or wine tannin extracts in model wine, the
      concentration of 4 was found to decrease to levels very close to those observed
      with an untreated red wine. When white wine was heated at 45 degrees C, 4 was
      formed, indicating the presence of precursor forms. The amounts formed were much
      higher than those found in a commercial white wine. 4 was also observed in red
      wine heated to 45 degrees C, but the concentration produced was much less than
      that with white wine.

PMID- 15853406
TI  - Elucidation of the emulsification properties of sugar beet pectin.
AB  - A protocol has been developed to fractionate sugar beet pectin using hydrophobic
      affinity chromatography. Three samples eluted from the column using 4 M NaCl as
      solvent (fractions 1A, 1B, and 1C), two fractions eluted using 2 M NaCl
      (fractions 2A and 2B), and one fraction eluted using water (fraction 3). The
      fractions were shown to be very polydisperse, and differences between the GPC
      refractive index and UV absorbance (214 nm) elution profiles demonstrated
      chemical heterogeneity. They were found to contain significantly different
      proportions of protein (1A, 2.79%; 1B, 0.97%; 1C, 0.77%; 2A, 1.41%; 2B, 5.09%;
      and 3, 5.89%) and ferulic acid (approximately 1A, 0.5%; 1B, 0.5%; 1C, 0.9%; 2B,
      1.5%; and 3, 2%). The weight-average molecular mass, M(w), of the fractions also
      varied (1A, 153 kDa; 1B, 155 kDa; 1C, 306 kDa; 2A, 562 kDa; 2B, 470 kDa; 3, 282
      kDa). Three fractions, that is, 1A, 1B, and 3, produced orange oil emulsions with
      a relatively small droplet size that were stable over a period of weeks. The
      other three fractions (1C, 2A, and 2B with higher M(w) values) produced emulsions
      with an initially larger droplet size, and the droplet size increased
      considerably over time. The increased droplet size may be influenced by the
      viscosity of the aqueous continuous phase. There was no simple relationship
      between protein or ferulic acid content and emulsification ability. For example,
      fraction 1B, which contained the lowest proportion of both protein and ferulic
      acid, produced stable emulsions of similar droplet size to fraction 3, which
      contained the largest proportion of protein and ferulic acid. The role of protein
      in the emulsification process was investigated by measuring the amount of protein
      in the aqueous phase before and after emulsification. It was clearly demonstrated
      that proteinaceous material adsorbed at the oil-water interface. It is evident
      that the emulsification properties of sugar beet pectin are influenced by the
      accessibility of the protein and ferulic acid groups to the surface of the oil
      droplets, the proportion of ester groups, and the molecular mass distribution of
      the fractions.

PMID- 15853407
TI  - Effects of structure on radical-scavenging abilities and antioxidative activities
      of tea polyphenols: NMR analytical approach using 1,1-diphenyl-2-picrylhydrazyl
      radicals.
AB  - Tea (Camellia sinensis) leaves contain various antioxidants such as ascorbic acid
      (1) and polyphenols. This study tries to clarify the molecular mechanisms
      underlying the antioxidative and radical-scavenging activities of these
      antioxidants, and the reactivities of each antioxidant have been compared against
      that of the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH, 2) using
      nuclear magnetic resonance (NMR) analysis. Catechol (3) and (+)-taxifolin (4)
      were oxidized to o-quinone by 2. However, ethyl protocatechuate (5) and quercetin
      (6) were not oxidized to o-quinone, even though they possess a catechol
      structure. The radical-scavenging ability of o-dihydroxyl phenolic compounds with
      a conjugated olefinic double bond (e.g., 6) was superior to that of compounds
      without this bond (e.g., 4), whereas the ability of o-dihydroxyl phenolic
      compounds possessing a conjugated carbonyl bond (5) was inferior to that of
      compounds lacking this bond (3). Vicinal trihydroxyl phenolic compounds with a
      conjugated olefinic double bond [e.g., myricetin (7)] had an inferior scavenging
      ability as compared with compounds lacking this bond [e.g., pyrogallol (8)], but
      7 was a better scavenger than compounds with a conjugated carbonyl double bond
      [e.g., ethyl gallate (9)]. In addition, vicinal trihydroxyl phenolic compounds
      (e.g., 9) were superior to o-dihydroxyl phenolic compounds (e.g., 6). Finally, 1
      scavenged radicals more quickly than 8.

PMID- 15853408
TI  - Effect of pH on hemoglobin-catalyzed lipid oxidation in cod muscle membranes in
      vitro and in situ.
AB  - The effect of pH and hemoglobin on oxidation of the microsomal lipids of cod was
      determined in isolated microsomes and in washed cod muscle. An increase of
      hemoglobin concentration from 0.5 to 15 microM accelerated lipid oxidation in
      both systems. In cod microsomes the rate of lipid oxidation increased in the
      order pH 6.8 >> pH 7.6 > pH 8.4 > pH 6.0 > pH 3.5. However, in washed cod muscle
      a decrease of pH from 7.8 to 6.8 greatly increased the lag phase and decreased
      the rate of lipid oxidation. A further decrease in pH to 3.5 decreased the lag
      phase and increased the rate of lipid oxidation further. A decrease of pH from
      7.6 to 6.4 greatly reduced the affinity of hemoglobin for oxygen. Formation of
      methemoglobin due to autoxidation occurred more rapidly at pH 6.0 than at pH 7.5.
      Structural changes of the isolated microsomal membranes could be the reason for
      the unexpected slow lipid oxidation in microsomes at pH 6.0 and below.

PMID- 15853409
TI  - Functional properties of guava seed glutelins.
AB  - Five guava seed glutelin extracts were obtained with different buffer solutions:
      Na(2)B(4)O(7) alone (Glut.Bo) or containing SDS (Glut. BoSDS), 2-mercaptoethanol
      (Glut.Bo2-ME), or a combination of both (Glut. BoSDS2-ME) and NaOH (Glut.Na). All
      borate buffer solutions were at pH 10. The higher yield of glutelins corresponded
      to the Glut. BoSDS extract (81.9% dry basis) and the lower to Glut.Bo (6.8%). The
      functional properties of the five guava seed glutelin extracts were determined.
      Glut. BoSDS, Glut. BoSDS2-ME, and Glut.Na showed high values for several
      properties, including surface hydrophobicity (7.7, 10.8, and 0.6, respectively),
      solubility at pH 10 (91.1, 77.9, and 96.7, respectively), water-holding capacity
      at pH 3.6 (1.7, 2.5, and 2.8, respectively), emulsifying activity index (pH 10;
      503.5, 238.2, and 838.0, respectively), and foaming properties (pH 10; V(0) =
      0.14, 0.25, and 0.19, respectively; V(max) = 6.1, 5.59, and 4.51, respectively;
      t(1/2) = 266, 255.3, and 94 s, respectively). These results suggest that the
      denaturing reagent (SDS or NaOH) during extraction conferred on the proteins a
      structure that facilitated the development of their functional properties.

PMID- 15853410
TI  - Plasma-enhanced modification of xanthan gum and its effect on rheological
      properties.
AB  - The structure and rheological properties of xanthan gum (XG) modified in a cold
      plasma environment were investigated. XG was functionalized in a capacitively
      coupled 13.56-MHz radio frequency dichlorosilane (DS)-plasma conditions and,
      consecutively, in situ aminated by ethylenediamine. The surface structure of
      modified XG was evaluated on the basis of survey and high-resolution ESCA, FTIR,
      and fluorescence labeling techniques. The types of species generated in DS-plasma
      were reported using residual gas analysis (RGA). The aqueous solutions of
      modified XG were cross-linked and cured at room temperature to form stable gels.
      The dynamic rheological characteristics of virgin XG and functionalized and cross
      linked XG were compared. It was found that parameters such as plasma treatment
      time and concentration of solutions can be optimized to form stable gels of XG.
      Thus, cold plasma technology is a novel, efficient, and nonenzymatic route to
      modify XG.

PMID- 15853411
TI  - Quantitation of nine organic acids in wild mushrooms.
AB  - The organic acids composition of six wild edible mushroom species (Amanita
      caesarea, Boletus edulis, Gyroporus castaneus, Lactarius deliciosus, Suillus
      collinitus, and Xerocomus chrysenteron) was determined by an HPLC-UV detector
      method. The results showed that all of the samples presented a profile composed
      of at least five organic acids: citric, ketoglutaric, malic, succinic, and
      fumaric acids. Several samples also contained oxalic, ascorbic, quinic, and
      shikimic acids. In a general way, the quantitation of the identified compounds
      indicated that malic acid, followed by the pair citric plus ketoglutaric acids,
      were the main compounds in the analyzed species, with the exception of A.
      caesarea, in which malic and ascorbic acids were the most abundant compounds. The
      relative amounts and the presence/absence of each identified compound may be
      useful for the differentiation of the species.

PMID- 15853412
TI  - Influence of dietary genistein levels on tissue genistein deposition and on the
      physical, chemical, and sensory quality of rainbow trout, Oncorhynchus mykiss.
AB  - Genistein, the primary isoflavone in soybean, is one of the chemical components
      responsible for some of the off-flavors associated with soy-based foods. The
      potential effects of genistein on the sensory and chemical quality of fish muscle
      may affect the full utilization of soybean meal as an alternative protein in
      aquaculture diets. Fingerling trout fed commercial diets containing 0, 500, 1000,
      or 3000 ppm pure genistein were analyzed after 6 and 12 months of feeding.
      Genistein was extracted by enzymatic digestions in Tris buffer and quantified by
      high-performance liquid chromatography. Moisture, fat, protein, ash, and
      tristimulus color of the fillets were determined. The extent of lipid oxidation
      occurring in fillets harvested after 12 months of feeding was studied by
      measurements of thiobarbituric acid reactive substances (TBARS) after 4 and 8
      days of refrigerated storage at 4 degrees C. Triangle tests were performed to
      determine if there were any detectable sensory differences. A dietary genistein
      content of 3000 ppm led to the deposition of approximately 5.4 pmol of
      genistein/mg of fillet. Triangle test panelists were unable to detect any
      significant (p < or = 0.05) differences between the fillets from trout fed the 0
      and 3000 ppm genistein concentrations. Moisture, ash, and protein content were
      influenced by time of harvest, while color was unaffected. TBARS levels on days 4
      and 8 were significantly (p < 0.05) higher in the fillets from the 0 ppm
      genistein level than in fillets from fish fed dietary genistein.

PMID- 15853413
TI  - Inhibition of induced DNA oxidative damage by beers: correlation with the content
      of polyphenols and melanoidins.
AB  - Beers are a source of dietary flavonoids; however, there exist differences in
      composition, alcohol concentration, and beneficial activities. To characterize
      these differences, three kinds of lager beer of habitual consumption in Spain,
      dark, blond, and alcohol-free, were assayed for total phenolic content,
      antioxidant activity, superoxide and hydroxyl radical scavenging activities, and
      in vitro inhibitory effect on DNA oxidative damage. Furthermore, their melanoidin
      content and correlation with antioxidant activity were evaluated. Dark beer
      contained the highest total phenolic (489 +/- 52 mg/L) and melanoidin (1.49 +/-
      0.02 g/L) contents with a 2-fold difference observed when compared to the alcohol
      free beer. For the three kinds of beer, the antioxidant activity measured as N,N
      dimethyl-p-phenylenediamine dihydrochloride concentration was strongly correlated
      with the total polyphenol content (R(2) = 0.91102, p < 0.005) and with the
      melanoidin content (R(2) = 0.7999, p < 0.05). The results support a positive
      effect of beers on the protection of DNA oxidative damage, by decreasing the
      deoxyribose degradation, DNA scission (measured by electrophoresis), and
      inhibition of 8-hydroxydeoxyguanosine (8-OH-dG) formation. Furthermore, a
      correlation between the total melanoidin content (R(2) = 0.7309, p < 0.01) and
      inhibition of 8-OH-dG was observed.

PMID- 15853414
TI  - Properties of tilapia carboxy- and oxyhemoglobin at postmortem pH.
AB  - Hemoglobin plays an important role in the color and oxidative stability of
      seafoods. A recent practice in the seafood industry is to stabilize muscle color
      by the application of gases containing carbon monoxide. The goal of this study
      was to examine and compare the properties of tilapia hemoglobin complexed to
      either O(2) (Oxy-Hb) or CO (CO-Hb) at pH 6.5, which reflects the tilapia muscle
      postmortem pH. CO-Hb was significantly (p < 0.01) more stable against
      autoxidation compared to Oxy-Hb when kept at 4 and -30 degrees C for 23 days.
      Almost no loss of CO was detected for both temperatures according to the UV-vis
      spectra of Hb. This stabilization was also believed to play a role in increased
      protein structure stabilization (p < 0.001) since less protein aggregation was
      seen for CO-Hb. The higher protein stabilization for Hb was linked to the heme
      group, which was maintained in its reduced state longer for CO-Hb vs Oxy-Hb and
      was likely less exposed to solvent. CO-Hb had significantly (p < 0.01) less
      peroxidase activity than Oxy-Hb and thus reactivity with H(2)O(2). The pro
      oxidative activity of CO-Hb was significantly (p < 0.01) reduced in a linoleic
      acid micelle system compared to that of Oxy-Hb, while smaller differences in
      activity were seen in a washed cod and tilapia muscle model system.

PMID- 15853415
TI  - Structure-function relationships of soybean proglycinins at subunit levels.
AB  - Glycinin consists of five kinds of subunits, group I (A1aB1b, A1bB2, and A2B1a)
      and group II (A3B4 and A5A4B3). cDNAs for individual subunits were cloned by
      reverse transcription-polymerase chain reaction method and expressed in
      Escherichia coli using pET vector. The recombinant proglycinins were purified by
      ammonium sulfate fractionation and column chromatography in the form of
      homotrimers. Physicochemical properties such as molecular dimensions, solubility,
      surface hydrophobicity, thermal stability, and emulsifying ability of individual
      proglycinins were studied. Molecular dimensions were proportional to molecular
      size for all proglycinins except A2B1a. Solubility was intrinsic to each
      proglycinin. At the ionic strength of 0.5, all proglycinins except A1aB1b showed
      a very low solubility at acidic pH, but A1aB1b was soluble to higher than 60%. At
      ionic strength 0.08, all proglycinins exhibited isoelectric precipitation,
      although A2B1a and A1bB2 were not completely insoluble. The order of emulsifying
      ability (A1bB2 < A2B1a < A5A4B3 < A3B4 < or = A1aB1b) was not of the same for
      surface hydrophobicity (A5A4B3 < A1aB1b < or = A3B4 < A1bB2 < A2B1a) and thermal
      stability (A1bB2 << A2B1a < or = A5A4B3 < A3B4 < or = A1aB1b).

PMID- 15853416
TI  - Molecular analysis and physicochemical properties of electrophoretic variants of
      wild soybean Glycine soja storage proteins.
AB  - Cultivated soybeans (Glycine max) are derived from wild soybeans (Glycine soja)
      and can be crossed with them to produce fertile offspring. The latter exhibit
      greater genetic variation than the former, suggesting a possibility that wild
      soybeans contain storage proteins with properties different from and better than
      those of cultivated soybeans. To identify a wild soybean suitable for breeding a
      new soybean cultivar, we analyzed seed proteins from 390 lines of wild soybeans
      by electrophoresis. We found some lines containing electrophoretic variants of
      glycinin and beta-conglycinin subunits: one line containing a small alpha'
      subunit of beta-conglycinin and two and five lines containing small A3 and large
      A4 polypeptides of glycinin, respectively. Beta-Conglycinin and glycinin
      containing such variant subunits exhibited solubility and emulsifying ability
      similar to those of the predominant types of wild and cultivated soybeans.
      Glycinins containing small A3 and large A4 gave a shoulder derived from the start
      of denaturation at a temperature 4 degrees C lower than that of glycinin from the
      predominant types of wild and cultivated soybeans, although their thermal
      denaturation midpoint temperatures were very similar to each other. Cloning and
      sequencing of the predominant and variant subunit cDNAs revealed that the small
      alpha' and the small A3 lacked 24 amino acid residues in the extension region and
      four amino acid residues in the hypervariable region, respectively, and that the
      large A4 did not have an insert corresponding to the difference in the
      electrophoretic mobility but Arg279 and Gln305 were replaced by glutamine and
      histidine, respectively, in the hypervariable region. These suggest that small
      differences even in the hypervariable region can affect the thermal stability, as
      well as the electrophoretic mobilities, of the proteins.

PMID- 15853417
TI  - Purification and partial characterization of lipoxygenase from desert truffle
      (Terfezia claveryi Chatin) ascocarps.
AB  - A lipoxygenase from Terfezia claveryi Chatin ascocarp, a mycorrhizal hypogeous
      fungus, is described for the first time. The higher proportion of PUFA in T.
      claveryi ascocarps makes lipid rancidity the main factor limiting its storage
      life. Thus, the studies on LOX from T. claveryi are important because this
      enzyme, among other roles, may be involved in an alteration of lipids leading to
      consumer rejection. The enzyme has been purified to apparent homogeneity by phase
      partitioning in the presence of Triton X-114, followed by two steps of cation
      exchange chromatography. The purified T. claveryi LOX preparation consisted of a
      single major band with an apparent molecular mass of 66 kDa after sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis. The enzymic activity exhibited a
      strong specificity toward linoleic and linolenic acids as substrates, while only
      32% activity was observed using gamma-linolenic acid. The pH optimum of this
      enzyme was pH 7.0. When the enzyme reacted with linoleic acid, it produced a
      single peak, which comigrated with standard 13-hydroperoxy-octadecadienoic acid;
      13-hydroperoxy-octadecatrienoic acid was produced during the reaction with
      linolenic acid.

PMID- 15853418
TI  - Vacuolar invertases in sweet potato: molecular cloning, characterization, and
      analysis of gene expression.
AB  - Two cDNAs (Ib beta fruct2 and Ib beta fruct3) encoding vacuolar invertases were
      cloned from sweet potato leaves, expressed in Pichia pastoris, and the
      recombinant proteins were purified by ammonium sulfate fractionation and
      chromatography on Ni-NTA agarose. The deduced amino acid sequences encoded by the
      cDNAs contained characteristic conserved elements of vacuolar invertases,
      including the sequence R[G/A/P]xxxGVS[E/D/M]K[S/T/A/R], located in the prepeptide
      region, Wxxx[M/I/V]LxWQ, located around the starting site of the mature protein,
      and an intact beta-fructosidase motif. The pH optimum, the substrate specificity,
      and the apparent K(m) values for sucrose exhibited by the recombinant proteins
      were similar to those of vacuolar invertases purified from sweet potato leaves
      and cell suspensions, thus confirming that the proteins encoded by Ib beta fruct2
      and Ib beta fruct3 are vacuolar invertases. Moreover, northern analysis revealed
      that the expression of the two genes was differentially regulated. With the
      exception of mature leaves and sprouting storage roots, Ib beta fruct2 mRNA is
      widely expressed among the tissues of the sweet potato and is more abundant in
      young sink tissues. By contrast, Ib beta fruct3 mRNA was only detected in shoots
      and in young and mature leaves. It appears, therefore, that these two vacuolar
      invertases play different physiological roles during the development of the sweet
      potato plant.

PMID- 15853419
TI  - Deactivation of triplet-excited riboflavin by purine derivatives: important role
      of uric acid in light-induced oxidation of milk sensitized by riboflavin.
AB  - The reactivity of purine derivatives (uric acid, xanthine, hypoxanthine, and
      purine) toward triplet-excited riboflavin in aqueous solution at pH 6.4 is
      described on the basis of kinetic (laser flash photolysis), electrochemical
      (square-wave voltammetry), and theoretical data (density functional theory, DFT).
      Direct deactivation of triplet-excited riboflavin in aqueous solution, pH 6.4 at
      24 degrees C, in the presence of uric acid, xanthine, and hypoxanthine strongly
      suggests a direct electron transfer from the purine to the triplet-excited
      riboflavin with k = 2.9 x 10(9) M(-1) s(-1) (DeltaH(++) = 14.7 kJ mol(-1),
      DeltaS(++) = -15.6 J mol(-1) K(-1)), 1.2 x 10(9) M(-1) s(-1) (DeltaH(++) = 34.3
      kJ mol(-1), DeltaS(++) = +45.3 J mol(-1) K(-1)), and 1.7 x10(8) M(-1) s(-1)
      (DeltaH(++) = 122 kJ mol(-1), DeltaS(++) = +319 J mol(-1) K(-1)), respectively.
      From the respective one-electron oxidation potentials collected in aqueous
      solution at pH 6.4 for uric acid (E = +0.686 vs normal hydrogen electrode, NHE),
      xanthine (E = +1.106 vs NHE), and hypoxanthine (E = +1.654 vs NHE), the overall
      free energy changes for electron transfer from the quencher to the triplet
      excited riboflavin are as follows: uric acid (DeltaG(o) = -114 kJ mol(-1)),
      xanthine (DeltaG(o) = -73.5 kJ mol(-1)), hypoxanthine (DeltaG(o) = -20.6 kJ mol(
      1)), and purine (DeltaG(o) > 0). The inertness observed for purine toward triplet
      excited riboflavin corroborates with its electrochemical inactivity in the
      potential range from 0 up to 2 V vs NHE. These data are in agreement with the DFT
      results, which show that the energy of the purine highest occupied molecular
      orbital (HOMO) (-0.2685 arbitrary unit) is lower than the energy of the
      semioccupied molecular orbital (SOMO) (-0.2557 a.u.) of triplet-excited
      riboflavin, indicating an endergonic process for the electron-transfer process.
      The rate-determining step for deactivation by purine derivatives can be assigned
      to an electron transfer from the purine derivative to the SOMO orbital of the
      triplet-excited riboflavin. The results show that uric acid may compete with
      oxygen and other antioxidants to deactivate triplet-excited riboflavin in milk
      serum and other biological fluids leading to a free radical process.

PMID- 15853420
TI  - Pleiotropic effect of phenolic compounds content increases in transgenic flax
      plant.
AB  - The principal goal of this paper was to generate flax (Linum usitatissimum L.)
      plants with increased antioxidant properties. To accomplish this a vector
      containing a multigene construct was prepared, and transgenic plants
      overexpressing essential flavonoid biosynthesis pathway enzymes were generated
      and analyzed. The simultaneous expression of genes encoding chalcone synthase
      (CHS), chalcone isomerase (CHI), and dihydroflavonol reductase (DFR) resulted in
      a significant increase of flax antioxidant capacity. To investigate the
      determinants of higher antioxidant properties of transgenic plants, the phenolic
      acids and lignans compound contents were measured. In both green part and seed
      extracts from transgenic plants, the phenolic acids level was increased when
      compared to the control. The calculated correlation coefficient between phenolic
      acids content and antioxidant capacity (0.82 and 0.70 for green part and
      flaxseed, respectively) perfectly reflects their strong relationship. The
      increase in yield of transgenic plants and their higher resistance to Fusarium
      culmorum and Fusarium oxysporum when compared to the control plants was a
      characteristic feature. It was assessed a very high correlation (correlation
      coefficient = 0.9) between phenolic acids level in flaxseed extract and
      resistance to F. culmorum. The flowering date of transgenic plants was
      approximately 3 weeks earlier than that of the control plants. Interestingly, a
      significant increase in monounsaturated fatty acids and a slight increase in
      lignans content accompanied the increase in antioxidant properties of flaxseeds.

PMID- 15853421
TI  - Simplified preparation of coniferyl and sinapyl alcohols.
AB  - Coniferyl and sinapyl alcohols were prepared from commercially available
      coniferaldehyde and sinapaldehyde using borohydride exchange resin in methanol.
      This reduction is highly regioselective and exceptionally simple, making these
      valuable monolignols readily available to researchers lacking synthetic chemistry
      expertise.

PMID- 15853422
TI  - Effect of chitosan on the biological properties of sweet basil (Ocimum basilicum
      L.).
AB  - The effect of the treatment of chitosan at various concentrations (0.01%, 0.05%,
      0.1%, 0.5%, and 1%) upon sweet basil (Ocimum basilicum L.) before seeding and
      transplanting was investigated in aspects of the amount of phenolic and terpenic
      compounds, antioxidant activity, and growth of the basil, as well as the
      phenylalanine ammonia lyase (PAL) activity. The total amount of the phenolic and
      terpenic compounds increased after the chitosan treatment. Especially, the
      amounts of rosmarinic acid (RA) and eugenol increased 2.5 times and 2 times,
      respectively, by 0.1% and 0.5% chitosan treatment. Due to the significant
      induction of phenolic compounds, especially RA, the corresponding antioxidant
      activity assayed by the DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical
      scavenging test increased at least 3.5-fold. Also, the activity of PAL, a key
      regulatory enzyme for the phenylpropanoid pathway, increased 32 times by 0.5%
      chitosan solution. Moreover, after the elicitor chitosan treatment, the growth in
      terms of the weight and height of the sweet basil significantly increased about
      17% and 12%, respectively. Our study demonstrates that an elicitor such as
      chitosan can effectively induce phytochemicals in plants, which might be another
      alternative and effective means instead of genetic modification.

PMID- 15853423
TI  - Mushroom tyrosinase: catalase activity, inhibition, and suicide inactivation.
AB  - Mushroom tyrosinase exhibits catalase activity with hydrogen peroxide (H(2)O(2))
      as substrate. In the absence of a one-electron donor substrate, H(2)O(2) is able
      to act as both oxidizing and reducing substrate. The kinetic parameters V(max)
      and K(m) that characterize the reaction were determined from the initial rates of
      oxygen gas production (V(0)(O)()2) under anaerobic conditions. The reaction can
      start from either of the two enzyme species present under anaerobic conditions:
      met-tyrosinase (E(m)) and deoxy-tyrosinase (E(d)). Thus, a molecule of H(2)O(2)
      can reduce E(m) to E(d) via the formation of oxy-tyrosinase (E(ox)) (E(m) + H(2)
      <==> O(2) right harpoon over left harpoon E(ox)), E(ox) releases oxygen into the
      medium and is transformed into E(d), which upon binding another molecule of
      H(2)O(2) is oxidized to E(m). The effect of pH and the action of inhibitors have
      also been studied. Catalase activity is favored by increased pH, with an optimum
      at pH = 6.4. Inhibitors that are analogues of o-diphenol, binding to the active
      site coppers diaxially, do not inhibit catalase activity but do reduce
      diphenolase activity. However, chloride, which binds in the equatorial
      orientation to the protonated enzyme (E(m)H), inhibits both catalase and
      diphenolase activities. Suicide inactivation of the enzyme by H(2)O(2) has been
      demonstrated. A kinetic mechanism that is supported by the experimental results
      is presented and discussed.

PMID- 15853424
TI  - Black and green teas equally inhibit diabetic cataracts in a streptozotocin
      induced rat model of diabetes.
AB  - Green and black teas were given at 1.25% in the drinking water to streptozotocin
      induced diabetic rats for 3 months. Normal and diabetic control groups were also
      studied. As expected, diabetic animals had significantly increased glucose in
      lens and plasma. Lens and red blood cell sorbitol were significantly increased as
      a result of the aldose reductase pathway activation. Plasma and lens lipid
      thiobarbituric acid-reactive substances and protein glycation were also
      significantly elevated. Both teas significantly inhibited diabetic cataracts and
      caused significant reductions in the biochemical pathway implicated in the
      development of the pathology. After corrections for glucose, it was found that
      the teas retard the development of diabetic cataracts by a hypoglycemic effect
      that in turn inhibits the biochemical indicators of pathology. There were
      significant correlations between glucose, cataract score, and these indicators.
      Green tea but not black tea caused a significant decline in triglycerides in the
      diabetic animals. Tea may be a simple, inexpensive means of preventing or
      retarding human diabetes and the ensuing complications. Tea also should be
      investigated as an adjunct therapy for diabetes treatment.

PMID- 15853425
TI  - Chlorogenic acid moderately decreases the quality of whey proteins in rats.
AB  - During processing and storage, phenolic compounds (PCs) may react with food
      protein bound amino acids (AAs). Such reactions have been reported to change
      physicochemical and to decrease in vitro digestion properties of proteins. A rat
      growth and nitrogen (N) balance study was conducted to prove whether
      derivatization with chlorogenic acid (CA) affects the nutritional quality of beta
      lactoglobulin (beta-LG). Test diets (10% protein level) contained nonderivatized
      beta-LG (LG, treated under omission of CA), low derivatization level beta-LG
      (LGL), high derivatization level beta-LG (LGH), or casein supplemented with l
      methionine (0.3% of diet; C+met) as an internal standard. An additional group
      received untreated beta-LG supplemented with pure CA (1.03% of diet; LG+CA). The
      AA composition of test proteins, plasma AAs, and liver glutathione (GSH)
      concentrations were determined. Protein digestibility-corrected amino acid score
      (PDCAAS) was calculated using human or rat AA requirement patterns and rat fecal
      digestibility values. N excretion was significantly higher in feces and lower in
      urine of rats fed with LGH as compared to LG and LGL. Consequently, true N
      digestibility (TND) was significantly lower with LGH as compared to LG and LGL.
      The lower content of methionine, cysteine, lysine, and tryptophan in LGH
      corresponded to a reduced TND. Net protein utilization (NPU) was not different
      between treated beta-LG fed diet groups but was lower than in LG+CA and C+met fed
      groups. Only at a relatively high level of derivatization with CA, the otherwise
      good nutritional quality of beta-LG is affected so that TND is reduced, while NPU
      still remains unaffected. Derivatization of beta-LG with CA does not seem to lead
      to an additional deficiency in a specific indispensable AA in growing rats fed
      with 10% protein.

PMID- 15853426
TI  - Bioavailability of calcium from milk-based formulas and fruit juices containing
      milk and cereals estimated by in vitro methods (solubility, dialyzability, and
      uptake and transport by caco-2 cells).
AB  - An adequate calcium intake during the first years of life is needed for normal
      growth and development and to prevent rickets. The bioavailability of calcium
      from infant foods (milk-based formulas and fruit juices containing milk and
      cereals, FMC), the dietary sources of calcium in these stages of life, has been
      estimated on the basis of simulated gastrointestinal digestion and calcium
      solubility and dialyzability values and on the efficiency of transport and uptake
      by Caco-2 cells. The ranking of samples according to calcium bioavailability
      depends on the use of solubility or dialyzability as criterion. On the basis of
      the former, the highest value corresponded to adapted formulas and the lowest to
      fruit juices. However, when using percentage dialysis, the highest value
      corresponded to fruit juices and the lowest to follow-up formulas. The highest
      percentages of transport efficiency and uptake by Caco-2 cells corresponded to
      calcium from the analyzed fruit juices, followed by toddler, follow-up, and
      adapted formulas.

PMID- 15853427
TI  - Esterified whey proteins can protect Lactococcus lactis against bacteriophage
      infection. Comparison with the effect of native basic proteins and L-polylysines.
AB  - Inhibitory action of basic esterified milk whey proteins [methylated (Met) or
      ethylated (Et) beta-lactoglobulin (BLG) and alpha-lactalbumin (ALA)], basic
      native proteins (chicken egg white lysozyme and calf thymus histone), and basic
      protein-like substances (L-polylysines) against the activity and replication of
      lactococcal bacteriophages (bIL66, bIL67, and bIL170) was tested. Chemical
      interactions of these proteins with phage DNA were determined as well as their
      protective effect on the growth of a laboratory plasmid-cured Lactococcus lactis
      subjected to an infection by the bacteriophages. All the proteins studied showed
      inhibitory activity against the three bacteriophages as tested by marked
      reduction of their lytic activities and decreasing the replication of studied
      phages. Histone and Met-BLG were more active toward bIL66 and bIL67,
      respectively, while both proteins were highly and equally active toward bIL170.
      Lysozyme showed lower antiviral activity. Antiviral activity of Et-BLG was a
      little bit lower than that observed in the case of the Met derivative. Esterified
      ALA also showed considerable but slightly lower antiviral activity as compared to
      other proteins. L-polylysines also showed an antiviral effect against the three
      bacteriophages studied, their influence being highly dependent on their molecular
      size. The best effective size of L-polylysines was in the range 15-70 kDa.
      Replication of bIL67 was inhibited by the presence of esterified ALA or BLG and
      native basic proteins. Complete inhibition of replication of bIL67 occurred when
      using polylysines with molecular masses in the ranges 4-15, 15-30, and 30-70 kDa,
      while protein-like substrates with lower molecular masses had only a slight
      effect. The presence of histone and Met-BLG at a concentration of 0.13 mg/mL in
      the incubation medium protected L. lactis against lysis when it was subjected to
      an infection by bIL67 (10(5) pfu/mL). The same action was achieved by l
      polylysine (15-30 kDa) used at a concentration of 0.03 mg/mL in the incubation
      medium.

PMID- 15853428
TI  - Use of fatty acid profiles to identify food-borne bacterial pathogens and aerobic
      endospore-forming bacilli.
AB  - Capillary gas chromatography (GC) with flame ionization detection was used to
      determine the cellular fatty acid profiles of various food-borne microbial
      pathogens and to compare the fatty acid profiles of spores and vegetative cells
      of the same endospore-forming bacilli. Fifteen bacteria, representing eight
      genera (Staphylococcus, Listeria, Bacillus, Yersinia, Salmonella, Shigella,
      Escherichia, and Vibrio) and 11 species were used to compare the extracted fatty
      acid methyl esters (FAMEs). Endospore-forming bacilli were processed to obtain
      pure spores and whole cell FAMEs for GC analysis. A data set for each bacterial
      agent was prepared using fatty acid profiles from five replicates prepared on
      different days. The results showed that these fatty acid intensity profiles were
      unique for each of the 11 species and that they could be used as a fingerprint
      for the organisms. The cellular fatty acid profiles for Bacillus anthracis and
      Bacillus cereus show that there are two branched chain fatty acids, iso 17:1
      omega10c and 17:1 anteiso, which are unique in these species. Iso 17:1 omega10c
      is present in B. cereus vegetative cells and spores but is not observed in B.
      anthracis. The 17:1 anteiso fatty acid is present in B. anthracis cells but not
      in B. cereus cells. Fatty acids 16:0 2OH and 17:0 iso 3OH are present in B.
      anthracis and B. cereus spores but not in the vegetative cells. In summary,
      analysis of FAMEs from bacteria and spores can provide a sensitive procedure for
      the identification of food-borne pathogens.

PMID- 15853429
TI  - Modification of IgE binding to beta-lactoglobulin by fermentation and proteolysis
      of cow's milk.
AB  - The effect of fermentation by Lactobacilli and of proteolytic hydrolysis of whole
      milk on the IgE binding ability of beta-lactoglobulin was studied using an ELISA
      inhibition assay. Sera from nine adult milk allergic patients were tested. The
      individual sera showed a similar inhibition pattern in the changes during
      fermentation and proteolysis. The degradation of beta-lactoglobulin was studied
      with liquid chromatography. In general, fermentation with Lactobacilli gave
      little effect on IgE binding, even though chromatography data showed a gradual
      degradation of beta-lactoglobulin. Proteolysis with trypsin, however, gave
      extensive degradation of beta-lactoglobulin and strongly decreased IgE binding.
      In addition, we measured the inhibition pattern of beta-lactoglobulin in various
      selected commercially available fermented milk products. These showed an IgE
      binding capacity similar to that of nonfermented high pasteurized milk.

PMID- 15853430
TI  - Comment on cube resin insecticide: identification and biological activity of 29
      rotenoid constituents.

PMID- 15853431
TI  - Meningococcal vaccination: cui bono?

PMID- 15853432
TI  - Future challenges for the economic evaluation of healthcare: patient preferences,
      risk attitudes and beyond.
AB  - The continued growth in the economic evaluation of healthcare over the past 25
      years has led to a shortage of trained health economists globally, leading to a
      number of universities and/or national governments developing specialised health
      economics programmes to train more health economists. One of the common problems
      with many of these training programmes is that they only educate new health
      economists to the Masters level, and as such they are unable to cover the many
      skills needed by a successful health economist. Furthermore, government and
      industry interests have ensured that economic evaluation is a heavily regulated
      environment that gives little incentive to seek further education. These two
      related factors (under-education and over-regulation) have lead to a situation
      where economic evaluation methods may adversely limit innovation of therapeutics
      and devices in clinical areas that perform badly when evaluated on the cost per
      QALY scale. The good news, however, is that the tide is turning and theoretically
      sound adjustments (such as risk adjustments and stated preferences) to the
      current paradigm are now being considered. This, of cause, is just the tip of the
      iceberg with other important issues such as time preference and the endogeneity
      of preference remaining very much under-researched areas in health. This paper
      concludes that many of these real-world issues, such as patient preferences, can
      be avoided by using artificial objective functions such as cost per QALY, but
      this comes at the cost of irrelevance and the misallocation of resources. If we
      are to meet all of the future challenges in economic evaluation in healthcare
      then we must focus more on advanced education and far less on the regulation of
      health economists.

PMID- 15853433
TI  - Pharmacoeconomic analyses using discrete event simulation.
AB  - To date, decision trees and Markov models have been the most common methods used
      in pharmacoeconomic evaluations. Both of these techniques lack the flexibility
      required to appropriately represent clinical reality. In this paper an
      alternative, more natural, way to model clinical reality--discrete event
      simulation--is presented and its application is illustrated with a real world
      example.A discrete event simulation represents the course of disease very
      naturally, with few restrictions. Neither mutually exclusive branches nor states
      are required, nor is a fixed cycle. All relevant aspects can be incorporated
      explicitly and efficiently. Flexibility in handling perspectives and carrying out
      sensitivity analyses, including structural variations, is incorporated and the
      entire model can be presented very transparently. The main limitations are
      imposed by lack of data to fit realistic models. Discrete event simulation,
      though rarely employed in pharmacoeconomics today, should be strongly considered
      when carrying out economic evaluations, particularly those aimed at informing
      policy makers and at estimating the budget impact of a pharmaceutical
      intervention.

PMID- 15853434
TI  - Review of the cost effectiveness of immunisation strategies for the control of
      epidemic meningococcal meningitis.
AB  - Outbreaks of meningococcal disease have caused devastation worldwide. Effective
      vaccines have not been used routinely, due to perceived limitations of the
      duration of effectiveness as well as immunogenicity when administered during
      infancy. Given the sporadic nature of outbreaks, the optimal use of these
      vaccines to control both short-term epidemic and endemic meningococcal disease
      has been the subject of much debate. Seven economic studies on the use of
      polysaccharide vaccination strategies help to highlight the relevant
      epidemiological and economic issues surrounding the decisions for their use. Five
      of these studies were based in Africa, the region where annual incidence rates
      can be several orders of magnitude greater than the rest of the world. These
      studies demonstrated that vaccination against meningococcal disease during
      outbreak situations is suboptimal given the inability to rapidly immunise
      populations in a timely fashion in resource-poor areas. However, depending on the
      disease incidence and the ability to deliver vaccines, the polysaccharide vaccine
      can be cost effective for preventive strategies when given prior to the start of
      outbreaks, either through presumptive vaccination or through a modified routine
      delivery strategy. Economic analyses of mass immunisation campaigns and modelled
      routine vaccination suggest that routine use of meningococcal vaccines for
      preventive strategies could be within the range of cost-effective public health
      interventions in those regions of the world where meningococcal disease is
      endemic. This includes the meningococcal belt of Africa, the Sahelian region.

PMID- 15853436
TI  - Cost effectiveness of budesonide/formoterol in a single inhaler for COPD compared
      with each monocomponent used alone.
AB  - OBJECTIVE: To compare the healthcare costs and effects of budesonide/formoterol
      in a single inhaler with those of budesonide and formoterol monotherapies, and
      placebo, in a multinational study in patients with chronic obstructive pulmonary
      disease (COPD), National Heart, Lung and Blood Institute (NHLBI)/WHO Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) stages III or IV. Previous
      analysis of the clinical data from the study had shown that budesonide/formoterol
      was associated with better lung function and improved health-related QOL compared
      with the monocomponents or placebo and lower frequency of exacerbations compared
      with formoterol and placebo. METHOD: Patients (n = 1022) were randomised to twice
      daily treatment with two inhalations of budesonide/formoterol (160 microg/4.5
      microg) in a single inhaler, budesonide 200 microg, formoterol 4.5 microg or
      placebo for 12 months. Data on medication and healthcare use were combined with
      Swedish unit cost data to estimate the total annual healthcare cost per patient
      from the Swedish healthcare payer perspective. Costs were valued in Swedish
      kronor (SEK) [2001 values] and converted to euros (SEK 1 = euro 0.11, 25th April
      2003). RESULTS: This evaluation estimated the total annual healthcare costs per
      patient to be numerically lower for budesonide/formoterol (euro 2518) than for
      budesonide (euro 3194), formoterol (euro 3653) or placebo (euro 3213). Cost
      effectiveness acceptability curves suggest that budesonide/formoterol may be cost
      effective compared with formoterol, even if the decision maker is not willing to
      pay anything for the additional clinical effects, and that budesonide/formoterol
      is cost effective compared with placebo if a decision maker is willing to pay
      about euro 2 per day, per avoided exacerbation. CONCLUSION: This economic
      analysis suggests that the clinical benefits of using budesonide/formoterol in a
      single inhaler are achieved at a numerically lower total healthcare cost than
      either monocomponent or placebo. Budesonide/formoterol in patients with severe
      COPD (GOLD stages III or IV) may be cost effective, from the healthcare provider
      perspective, compared with either monocomponent.

PMID- 15853435
TI  - Health-related QOL in acute exacerbations of chronic bronchitis and chronic
      obstructive pulmonary disease: a review of the literature.
AB  - There is a lack of emphasis on health-related QOL (HR-QOL) changes associated
      with acute exacerbation of chronic bronchitis (CB) or chronic obstructive
      pulmonary disease (COPD). The aim of this review is to examine the use of HR-QOL
      instruments to evaluate acute exacerbation of CB or COPD, so as to form
      recommendations for future research.A literature search of papers published
      between 1966 and July 2003 identified more than 300 articles that used acute
      exacerbation of CB or COPD as the search term. However, only 21 of these studies
      employed HR-QOL measures as predictors of outcome or in the assessment of the
      impact, evolution or treatment of acute exacerbations of COPD or CB. A variety of
      HR-QOL measures were used, both generic and disease specific. The disease
      specific St George's Respiratory Questionnaire (SGRQ), devised for patients with
      stable CB and with a recall period of 1-12 months, was the most widely used
      measure, with the Chronic Respiratory disease Questionnaire (CRQ) and the
      Baseline and Transitional Dyspnoea Index (BDI, TDI) being the only other disease
      specific measures used. Most measures, both generic and disease specific,
      performed adequately when used during acute exacerbation of CB or COPD and
      indicated poor HR-QOL during acute exacerbation, which improved on resolution of
      the exacerbation. Relationships were evident between HR-QOL during an acute
      exacerbation and various outcomes, including post-exacerbation functional status,
      hospital re- admission for acute exacerbation or COPD, and mortality. There is a
      need for studies of treatments for acute exacerbation of CB or COPD to include an
      appropriate HR-QOL instrument to aid in the stratification of patients so as to
      target the right treatment to the right patient group. While a new instrument
      could be developed to measure HR-QOL during acute exacerbation of CB or COPD,
      currently available disease-specific measures such as the CRQ and the SGRQ appear
      to be acceptable to patients during acute exacerbation. However, the recall
      period of the SGRQ symptoms component should be shortened to make it more
      appropriate for use during acute exacerbation.

PMID- 15853437
TI  - Modelling cost effectiveness and cost utility of sequential DMARD therapy
      including leflunomide in rheumatoid arthritis in Germany: I. Selected DMARDs and
      patient-related costs.
AB  - OBJECTIVE: To quantify direct costs of medication and cost of illness (according
      to functional capacity) for patients with rheumatoid arthritis (RA) in Germany,
      allowing further use in a health economic evaluation of sequential therapy with
      disease-modifying antirheumatic drugs (DMARDs) in specialised, i.e.
      rheumatological, care in Germany. DESIGN AND SETTING: The analysis was conducted
      from the societal perspective in Germany using a modelling approach, which was
      based on secondary analysis of existing data and on data from a sample of 583
      patients from the German rheumatological database of 1998. Functional capacity
      was defined by the Hannover Functional Ability Questionnaire (HFAQ) scores. Costs
      were calculated from resources utilised and patients' work capacity. Direct costs
      consisted of outpatient medical services, inpatient treatment, long-term care and
      rehabilitation treatment. Indirect costs incurred by sick leave and premature
      retirement were quantified according to the human-capital approach. MAIN OUTCOME
      MEASURES AND RESULTS: Average total direct costs (year 1998-2001 values) per
      patient per year for continuous treatment with the selected DMARDs comprising
      costs for drugs, monitoring and treatment of adverse drug reactions (ADRs) were
      highest for intramuscular gold (sodium aurothiomalate) [euro 2106 (euro 1
      approximately equal to $US 0.91; average of the period from 2000 through 2001)]
      followed by leflunomide (euro 2010), azathioprine (euro 1878), sulfasalazine
      (euro 1190), oral methotrexate (euro 708), and lowest for the antimalarials
      chloroquine/hydroxychloroquine (euro 684). There were additional yearly costs for
      RA-related non-DMARD medication of euro 554 per patient, including management of
      ADRs. Mean cost of illness (year 1998 values) excluding medication cost amounted
      to euro 17,868 per RA patient per year. Annual costs increased with increasing
      disability, i.e. decreasing functional capacity, of RA patients from euro 6029
      per patient with more than 94% of functional capacity to euro 28,509 per patient
      with <20% of functional capacity. In general, there was a predominance of
      indirect costs in each of the categories of functional capacity, ranging between
      74% and 87% of total (direct and indirect) annual costs per RA patient. Annual
      direct costs increased from euro 811 to euro 7438 per patient with increasing
      disability. Inpatient treatment was the predominant component of direct costs.
      Patients in the worst category (<20%) of function experienced hospital costs that
      were 6.5 times higher than those of patients in the best category (>94%).
      CONCLUSIONS: On the basis of the data presented it can be concluded that the
      results of this investigation are typical for patients in rheumatological care in
      Germany and can therefore be used in a health economic analysis of different
      DMARD sequences aimed at changing disease progression over time.

PMID- 15853438
TI  - Modelling cost effectiveness and cost utility of sequential DMARD therapy
      including leflunomide for rheumatoid arthritis in Germany: II. The contribution
      of leflunomide to efficiency.
AB  - OBJECTIVE: To estimate the 3-year incremental cost effectiveness and cost utility
      of introducing leflunomide into sequential therapy, consisting of the most
      frequently used disease-modifying antirheumatic drugs (DMARDs), for patients with
      rheumatoid arthritis in specialised, i.e. rheumatological, care in Germany.
      DESIGN AND SETTING: The analysis was conducted from the societal perspective in
      Germany using an existing 3-year simulation model, which was adapted to the
      German healthcare system after secondary analysis of relevant publications and
      data. DMARD sequences including leflunomide were compared with those excluding
      leflunomide. Costs comprised direct costs incurred by treatment and indirect
      costs incurred by loss of productivity (sick leave and premature retirement) of
      rheumatoid arthritis patients. Effectiveness parameters were given by response
      years gained (RYGs) according to the American College of Rheumatology (ACR)
      criteria for 20%, 50% and 70% improvement (ACR20/50/70RYGs) and by QALYs gained
      (QALYGs). Costs, effects and QALYs were discounted by 5% per annum. In the base
      case analysis, average values of costs, response years and QALYs were applied.
      Costs were in 1998-2001 values (euro 1 approximately equal to $US 0.91, average
      of the period from the year 2000 through 2001). MAIN OUTCOME MEASURES AND
      RESULTS: After 3 years, adding leflunomide was less costly and more effective
      than the strategy excluding leflunomide when total (direct and indirect) costs
      were considered. There were savings of euro 271,777 and 8.1, 4.3, 5.1 and 4.9
      ACR20RYGs, ACR50RYGs, ACR70RYGs and QALYGs per 100 patients, respectively,
      obtained through adding leflunomide. Focusing on direct costs, adding leflunomide
      was more costly and more effective compared with excluding leflunomide, with an
      incremental cost effectiveness of euro 5004 per ACR20RYG, euro 9535 per ACR50RYG,
      euro 7996 per ACR70RYG, and an incremental cost utility of euro8301 per QALYG,
      after 3 years. The robustness of the results was shown in comprehensive
      sensitivity analyses. In the analysis of extremes, different combinations of the
      limits of cost, effectiveness and utility parameters were investigated. Adding
      leflunomide to sequential DMARD therapy remained dominant in 79% of the possible
      cases, i.e. was less costly and more effective than the strategy excluding
      leflunomide. Focusing on direct costs, adding leflunomide became dominant in 29%
      and remained more costly and more effective in 50% of possible cases.
      CONCLUSIONS: Our analysis suggests, with its underlying data and assumptions,
      that having leflunomide as an additional option in a DMARD treatment sequence
      extends the time patients benefit from DMARD therapy at reasonable additional
      direct costs. Adding leflunomide may even be cost saving when total (direct and
      indirect) costs are considered. As data on DMARD effectiveness were extracted
      from the results of clinical trials, real-world data from observational studies
      would be needed to corroborate the findings of the present analysis.

PMID- 15853439
TI  - Potential determinants of drug-drug interaction associated dispensing in
      community pharmacies.
AB  - Although the number of clinically relevant drug-drug interactions (DDIs) is
      probably low, DDIs may be responsible for a substantial number of hospital
      admissions. In some countries, the pharmacist is responsible for preventing the
      use of unsafe or non-effective drug regimens. Specifically they should avoid the
      dispensing of combinations of drugs that may cause serious DDIs. In order to
      assess the determinants related to community pharmacies and associated with these
      dispensings, a systematic literature review was conducted. Medline and
      International Pharmaceutical Abstracts were searched for articles published in
      English between 1993 and 2003. Additional relevant articles were identified by
      screening the reference lists of relevant articles. Seven papers were located.
      The determinants described in the literature were divided into three groups. The
      first group focussed on the relationship between the pharmacist and the
      prescriber. The number of prescribers is of importance as well as the number of
      dispensing pharmacies. Both a high number of primary care physicians and multiple
      dispensing pharmacies increased the risk of DDIs. The availability, quality and
      sensitivity of the medication surveillance software appeared to be a second
      important determinant. Both too many and too few signals increased the risk of
      dispensing interacting drugs. The third group of determinants was related to the
      pharmacist and pharmacy organisation. Signals from the surveillance program are
      usually judged first by technicians and subsequently managed by the pharmacist.
      Consequently, knowledge, instructions and supervision are important determinants.
      A fourth group of determinants was identified in literature assessing
      interventions by pharmacists, including interventions for DDIs. A higher workload
      was associated with lower intervention rates, which indicated a higher risk of
      dispensing interacting drugs. The determinants identified in this review can be
      used to develop strategies to minimise patient harm resulting from DDIs. Further
      assessment of the relation between these determinants and the dispensing of DDIs
      and of the relation between DDI-associated dispensing and patient harm is
      recommended.

PMID- 15853440
TI  - The WHO World Alliance for Patient Safety: a new challenge or an old one
      neglected?
AB  - The WHO World Alliance on Patient Safety is a new, all encompassing project to
      improve medical care. Individual patients are the focus and all countries are
      encouraged to develop systems in which medical error, therapeutic accidents and
      failures are minimised. The potential for adverse events is present at all levels
      of healthcare and in all disciplines. One working group in the Alliance is
      charged with promoting and developing a 'reporting and learning' culture for
      adverse events in all areas of medical care. Central to current thinking for this
      group is a no-fault approach and to report near misses. The aim is not to provide
      certainty over the individual events, but rather to draw attention to possible
      improvements in systems that may prevent future problems. Adverse events relating
      to drug therapy have been reported for decades to national pharmacovigilance
      authorities, but this is aimed at finding problems with the drugs themselves as
      early as possible. The Alliance approach in the area of drug safety, by contrast,
      has a greater focus on safety in the systems of drug provision (including
      prescription and dispensing) and other systematic issues relating to safe drug
      provision, such as fraudulent drugs. Thus, current pharmacovigilance can be seen
      as representing a part of the reporting and learning envisaged by the Alliance.
      The two approaches are also complementary, but there are practical and
      philosophical areas of overlap in which difficulties may occur, such as
      anonymised reporting in a no-fault system and consequent impossibility for follow
      up. In pharmacovigilance follow-up for more information is regarded as essential.
      Whether pharmacovigilance broadens into the area of patient safety or the latter
      involves completely new systems to do its work will be a matter for each country
      to consider. One thing is certain, working together both systems will improve
      patient care, but without cooperation more bureaucracy will take valuable health
      professional time with a lesser result.

PMID- 15853441
TI  - The safety of herbal medicinal products derived from Echinacea species: a
      systematic review.
AB  - Echinacea spp. are native to North America and were traditionally used by the
      Indian tribes for a variety of ailments, including mouth sores, colds and snake
      bites. The three most commonly used Echinacea spp. are E. angustifolia, E.
      pallida and E. purpurea. Systematic literature searches were conducted in six
      electronic databases and the reference lists of all of the papers located were
      checked for further relevant publications. Information was also sought from the
      spontaneous reporting programmes of the WHO and national drug safety bodies.
      Twenty-three manufacturers of echinacea were contacted and asked for data held on
      file. Finally our own departmental files were searched. No language restrictions
      were imposed. Combination products and homeopathic preparations were excluded.
      Data from clinical studies and spontaneous reporting programmes suggest that
      adverse events with echinacea are not commonly reported. Gastrointestinal upsets
      and rashes occur most frequently. However, in rare cases, echinacea can be
      associated with allergic reactions that may be severe. Although there is a large
      amount of data that investigates the efficacy of echinacea, safety issues and the
      monitoring of adverse events have not been focused on. Short-term use of
      echinacea is associated with a relatively good safety profile, with a slight risk
      of transient, reversible, adverse events. The association of echinacea with
      allergic reactions is supported by the present evaluation. While these reactions
      are likely to be rare, patients with allergy or asthma should carefully consider
      their use of echinacea. The use of echinacea products during pregnancy and
      lactation would appear to be ill-advised in light of the paucity of data in this
      area.

PMID- 15853443
TI  - Benefit-risk assessment of irinotecan in advanced colorectal cancer.
AB  - Irinotecan exerts its cytotoxic activity through inhibition of the nuclear enzyme
      topoisomerase I. It has been approved in most countries worldwide for treatment
      of patients with advanced colorectal cancer (CRC). Activity is seen in previously
      untreated patients and in patients refractory to fluorouracil treatment, whether
      it is given alone or in combination with other cytotoxic drugs. Irinotecan was
      first developed in patients refractory to fluorouracil. Activity in terms of
      tumour responses and patient benefit was seen in several phase II trials that
      used either a weekly or a three-weekly schedule. In two randomised trials
      (irinotecan vs best supportive care, and irinotecan vs an infused fluorouracil
      based regimen), irinotecan prolonged median survival by approximately 2.5 months
      without any deterioration in quality-of-life. It was later studied in previously
      untreated patients with advanced CRC in combination with fluorouracil/folinic
      acid (leucovorin). In three large randomised trials, median time to tumour
      progression was prolonged by approximately 2.5 months and overall survival by
      about 2.5 months compared with fluorouracil/folinic acid alone. Tumour responses
      were also seen more frequently in the irinotecan arm (35-40% vs 20%). Again,
      quality-of-life scores were not deteriorated by the addition of irinotecan.
      Irinotecan has many acute adverse effects. The most prominent and dose limiting
      being diarrhoea and neutropenia. With irinotecan monotherapy, diarrhoea was seen
      in 80% of patients and severe grade 3 to 4 diarrhoea occurred in 30-40% of the
      patients. The severity of diarrhoea can be diminished by preventive actions. Less
      risk of diarrhoea is generally seen when irinotecan is combined with
      fluorouracil. Neutropenia is generally short-lived, but may be severe if
      diarrhoea is also present. This has been noticed particularly when irinotecan has
      been given in combination with a bolus fluorouracil/folinic acid regimen. Other
      toxicities include acute cholinergic-like symptoms, nausea and vomiting, and
      alopecia. In spite of these adverse effects, irinotecan has been accepted as an
      important first-line treatment for patients with advanced CRC, in combination
      with, preferably, an infused fluorouracil-based regimen, and has been approved
      for use as monotherapy in the second-line indication.

PMID- 15853442
TI  - Chemotherapy-induced ovarian failure: manifestations and management.
AB  - Thanks to improvements in treatment regimens, more and more patients are now
      surviving cancer. However, cancer survivors are faced with the serious long-term
      effects of the different modalities of cancer treatments. One of these adverse
      effects is chemotherapy-induced irreversible damage to the ovarian tissues, which
      leads to premature ovarian failure and its resulting consequences such as hot
      flashes, osteoporosis, sexual dysfunction and the risk of infertility.
      Chemotherapy-induced ovarian failure (or chemotherapy-induced premature
      menopause) affects the quality of life of female cancer survivors. Although there
      is no clear definition of chemotherapy-induced ovarian failure, irreversible
      amenorrhoea lasting for several months (>12 months) following chemotherapy and a
      follicle stimulating hormone level of > or = 30 MIU/mL in the presence of a
      negative pregnancy test seems to be an appropriate characterisation. Different
      chemotherapy agents, alkylating cytotoxics in particular, have the potential to
      cause progressive and irreversible damage to the ovaries. The result of this
      damage is a state of premature ovarian failure, with progressive declining of
      estrogen levels, decreasing bone mass and an increased risk of fractures.
      Historically, hormonal replacement therapy (HRT) has been used to treat
      menopausal problems in the general population, but concerns about the potential
      of estrogen to increase the risk of breast cancer in women at high-risk or
      increase the risk of recurrence in cancer survivors, have forced physicians to
      utilise alternative treatments. This review discusses some of the newer therapies
      that are now available to provide appropriate symptom control, avoid
      complications such as fractures and possibly prevent infertility by making the
      ovarian epithelium less susceptible to cytotoxic agents.

PMID- 15853444
TI  - Incidence of thrombotic cardiovascular events in patients taking celecoxib
      compared with those taking rofecoxib: interim results from the New Zealand
      Intensive Medicines Monitoring Programme.
AB  - BACKGROUND: Rofecoxib was withdrawn from the market worldwide because of concerns
      relating to cardiovascular safety. There is conflicting evidence as to whether
      celecoxib, the most popular alternative to rofecoxib, carries the same
      cardiovascular risks. This study's aim was to compare the incidence of thrombotic
      cardiovascular events in patients taking celecoxib with patients taking
      rofecoxib. METHODS: Prescription event monitoring methodology was used in this
      prospective, longitudinal, observational cohort study, in which cohorts of
      patients were established from prescription data and thrombotic cardiovascular
      events were identified from follow-up questionnaires to patients' doctors and
      other sources. SUBJECTS: New Zealand patients with at least one prescription for
      either rofecoxib or celecoxib between 1 December 2000 and 30 November 2001.
      ANALYSIS: For this interim analysis the total cohorts were separated into three
      groups at different stages of follow-up: complete, incomplete and no follow-up.
      Cox's proportional hazards models were applied to calculate hazard ratios for
      celecoxib compared with rofecoxib. RESULTS: The total cohorts included 26,403
      patients receiving rofecoxib and 32,446 patients receiving celecoxib. 4882 (18%)
      rofecoxib and 6267 (19%) celecoxib patients had been completely followed up. In
      this group the unadjusted hazard ratio for celecoxib compared with rofecoxib was
      1.07 (95% CI 0.59, 1.93). After adjustment for age this hazard ratio was 0.94
      (95% CI 0.51, 1.70). Further adjustment for sex, 'as required' use, indication
      for use, concomitant NSAID use and pre-existing cardiovascular disease resulted
      in only minor changes to the hazard ratio. CONCLUSION: This interim analysis of
      the Intensive Medicines Monitoring Programme data suggests that in 'real-life'
      postmarketing use in New Zealand there is no significant difference in the risk
      of cardiovascular thrombotic events in patients taking celecoxib compared with
      those taking rofecoxib.

PMID- 15853445
TI  - Retrospective analysis of the safety profile of oral moxifloxacin in elderly
      patients enrolled in clinical trials.
AB  - BACKGROUND AND OBJECTIVE: As aging is associated with physiological changes,
      including renal and hepatic insufficiency, and a higher risk of drug
      interactions, special attention needs to be directed towards the safety of
      medications in the elderly. The objective of this analysis was to evaluate the
      safety of oral moxifloxacin in elderly patients who were enrolled in clinical
      trials and to compare these results to those of other commonly used
      antibacterials. METHODS: Safety data from 27 prospective, randomised, comparative
      phase II/III trials of oral moxifloxacin included in the Bayer clinical trial
      database were pooled and analysed by age group (<65 years of age, 65-74 years of
      age, > or = 75 years of age) and by treatment group (moxifloxacin vs comparator).
      The primary endpoints included rates of treatment-emergent adverse events (all
      adverse events regardless of causality), drug-related adverse events, drug
      related serious adverse events, deaths and premature discontinuations because of
      a treatment-emergent adverse event. A treatment by age group interaction test was
      used to determine if the comparison between moxifloxacin and the comparator group
      in the incidence rates of any treatment-emergent or drug-related adverse events
      were affected by increasing age. RESULTS: Of the 12 231 patients who had valid
      safety data, 6270 had been treated with oral moxifloxacin and 5961 with a
      comparator antibacterial. The most frequently used comparators were cefuroxime
      and clarithromycin. Most patients (n = 9671) were <65 years of age (4939
      moxifloxacin, 4732 comparator); 1636 patients were 65-74 years of age (842
      moxifloxacin, 794 comparator); and 924 patients were > or = 75 years of age (489
      moxifloxacin, 435 comparator). The treatment by age group interaction test
      revealed that the comparison of drug-related adverse event rates between the
      moxifloxacin and comparator group were not affected by increasing age (p = 0.43).
      Rates of premature termination between the moxifloxacin and comparator treatment
      groups also did not increase with age (p = 0.552). No arrhythmias related to
      corrected QT (QTc) interval prolongation were reported following oral
      moxifloxacin or comparator treatment in this large group of young and elderly
      patients. Overall, the number of deaths was similar between the treatment groups
      (17 moxifloxacin, 19 comparator). CONCLUSIONS: Drug-related adverse event rates
      associated with oral moxifloxacin or the comparator therapy used in these studies
      did not significantly increase with advancing age. This pooled analysis suggests
      that oral moxifloxacin can be safely used in elderly patients with
      characteristics consistent with those enrolled into the clinical trials.

PMID- 15853446
TI  - Detecting adverse drug reactions on paediatric wards: intensified surveillance
      versus computerised screening of laboratory values.
AB  - BACKGROUND: Adverse drug reactions (ADRs) contribute significantly to patient
      morbidity and mortality, as well as to costs for healthcare systems. Our aim was
      to evaluate the type and incidence of ADRs in a paediatric hospital population,
      comparatively ascertained by two different methodological approaches. METHODS:
      Our prospective study enrolled all patients admitted to two of the general
      children wards (46 beds) and the paediatric intensive care unit (6 beds) at the
      HELIOS Klinikum Wuppertal teaching hospital in Germany, over the study period of
      3 months. We used two methods to detect ADRs. The intensified surveillance system
      relied on a trained physician conducting ward rounds and assessing patient
      charts. The computer-assisted screening of pathological laboratory parameters
      used values slightly below or above the age-specific normal range as a trigger
      signal for a potential ADR, which was subsequently assessed by trained personnel.
      RESULTS: By applying both methods simultaneously we observed that 14.1% of
      children experienced an ADR while they were hospitalised and 2.7% of children
      were admitted to hospital because of the ADR. Intensified surveillance resulted
      in the detection of 101 ADRs in 11.9% of patients, predominantly presenting with
      gastrointestinal symptoms, skin and CNS disorders; computer-assisted screening
      identified 45 ADRs in 5.7% of patients, mainly with drug-induced blood dyscrasia
      and liver damage. Furthermore, the ADRs detected by the intensified method were
      more severe, affected younger children and showed a closer causal attributability
      to the reaction than the ADRs observed by the computerised method. The spectra of
      drugs involved were similar, with the anti-infectives being suspected most
      frequently. The sensitivities of the intensified surveillance system and the
      computerised surveillance screening came to 67.2% and 44.8%, respectively, with
      computer-assisted screening having a specificity of 72.8%. The mean positive
      predictive value of the pathological laboratory values under surveillance by
      computer-assisted screening was 18.6%. Approximately 25% of ADR-related drugs
      administered were used for off-label indications. CONCLUSION: Using the published
      literature for comparison, we found that ADRs occur as frequently in paediatric
      patients as in adult patients. Intensified surveillance and computerised
      surveillance applied in the paediatric setting show substantial differences in
      their detection specificities. A higher number of and more severe ADRs can be
      detected by intensified surveillance than by computerised surveillance, but
      require higher personnel resources.

PMID- 15853447
TI  - Protective effects of an antioxidant derived from serine and vitamin B6 on skin
      photoaging in hairless mice.
AB  - The generation of reactive oxygen species (ROS) by ultraviolet radiation (UVR)
      accelerates skin aging, which is known as photoaging. Because cutaneous iron
      catalyzes ROS generation, sequestering iron by chelating agents is thought to be
      an effective approach toward preventing photoaging. Previously, N-(4
      pyridoxylmethylene)-l-serine (PYSer) was designed as an antioxidant to suppress
      iron-catalyzed ROS generation by its iron-sequestering activity. In this study,
      PYSer showed protective effects against skin damage in hairless mice irradiated
      with ultraviolet B (UV-B). Topical application of PYSer to the skin significantly
      delayed and/or decreased the visible wrinkle formation induced by chronic UV-B
      irradiation. A histological study indicated that UV-B-induced epidermal
      hypertrophy and lymphocytic infiltration were suppressed by PYSer. Moreover,
      PYSer showed suppressive activity against the UV-B-induced increase in
      glycosaminoglycans (GAG). These results indicate that PYSer is a promising
      antioxidant for the prevention of chronic skin photoaging by its iron
      sequestering activity.

PMID- 15853448
TI  - Temperature stress tolerance of conifer seedlings after exposure to UV-B
      radiation.
AB  - Ground-level UV-B radiation has increased globally due to a thinning
      stratospheric ozone layer. We estimated the effects of increased UV-B on 10
      conifer species grown in chambers in greenhouses with supplemental UV-B. Species
      were selected from a wide range of geographic locations. Plant material of two
      ages (germinants, first growing season; seedlings, second season) were exposed to
      three levels of UV-B from ambient (at Victoria, B.C., Canada) to three times
      ambient (12 kJ m(-2) d(-1)) for up to four months. Frost hardiness and heat
      tolerance of shoots were estimated from changes in chlorophyll fluorescence after
      exposure to test temperatures. There were no significant differences among seed
      sources from different elevations in their response to temperature stresses. When
      UV-B increased above the ambient level, three species (interior Douglas-fir,
      Engelmann spruce, and interior lodgepole pine) increased in frost hardiness and
      four (grand fir, interior spruce, yellow-cedar, and western redcedar) decreased.
      Two species (western redcedar and western hemlock) increased in heat tolerance
      when UV-B increased to the 12 kJ level. The main differences in stress tolerance
      were between the triple ambient and the other two treatments, not between ambient
      and double ambient, suggesting that any changes in UV-B would have to be large to
      elicit physiological changes in conifer seedlings.

PMID- 15853450
TI  - Interview with David S. Fedson, MD, Former Professor of Medicine, University of
      Virginia School of Medicine, and Director of Medical Affairs, Aventis Pasteur MSD
      by Madeline Drexler.

PMID- 15853451
TI  - Willingness of private physicians to be involved in smallpox preparedness and
      response activities.
AB  - BACKGROUND: The public health system continues its efforts to prepare for
      bioterrorist events, such as a smallpox outbreak, but may need to call on other
      health professionals to ensure sufficient capacity to implement preparedness
      plans. OBJECTIVE: The goal was to understand the willingness of primary care
      physicians to participate in possible smallpox pre- or post-event activities.
      METHODS: A 23-question mail survey was sent to a national random sample of 727
      internists and 720 family physicians. After three mailings, a one-page version of
      the survey was sent to nonrespondents. RESULTS: Response rates were 26% for
      questions common to both surveys and 22% for questions on the longer survey only.
      Respondents to the survey expressed moderate support for participating in certain
      smallpox pre- and post-event activities. Under a pre-event scenario, many
      providers would be willing to vaccinate first responders in their practice, and
      roughly one-third would be willing to vaccinate patients in their practice or to
      work in a public health clinic as a vaccinator. Most physicians, however, would
      be unwilling to be vaccinated themselves. Under post-event conditions, most
      providers would be willing to vaccinate their own patients, and many would
      vaccinate other community members in their practice. CONCLUSIONS: Despite the low
      response rate, information from this study on the smallpox preparedness
      activities in which physicians are most willing to participate can help to inform
      efforts by public health officials and private physicians to collaborate on
      bioterrorism preparedness efforts.

PMID- 15853452
TI  - Hospital decision-making regarding the smallpox pre-event vaccination program.
AB  - OBJECTIVES: To understand the factors underlying the decision by U.S. hospitals
      to participate or not in the U.S. Smallpox Pre-Event Vaccination Program (SPVP).
      METHODS: We conducted semistructured telephone interviews with a convenience
      sample of 123 hospital decision-makers in nine states between June and November
      2003. RESULTS: Within our sample, 88 hospitals (72%) decided to participate in
      the SPVP and 35 (28%) decided against doing so. Nearly all hospital decision
      makers considered the risk of a smallpox outbreak, risks associated with
      vaccination, hospital costs, and the reaction of hospital stakeholders. However,
      these factors often were weighed differently by hospitals that decided to
      participate compared to those that did not. Fewer than half of all hospitals
      reported that public health officials played an important role in their decision
      making process, but those that did felt the influence of public health officials
      was positive. CONCLUSIONS: Strengthening the linkage between the public and
      private health sectors may help to address some of the barriers to broader
      participation by hospitals in the SPVP and foster the success of smallpox
      outbreak response preparedness efforts in the future.

PMID- 15853453
TI  - Are public health workers aware of what they don't know?
AB  - OBJECTIVES: Training of public health workers is an important part of
      preparedness. Self-assessment is often used to measure how well workers are
      trained and whether they are ready to respond to an emergency event. The current
      study assessed how well self-assessment predicts actual knowledge. METHODS:
      Public health workers at a Public Health Ready pilot site self-assessed their
      general level of confidence, answered objective knowledge items about their local
      response plan, and self-assessed whether they were correct on the objective
      knowledge items. Correlational analysis was used to assess how well workers could
      assess what they knew and did not know. RESULTS: In the first analysis, for 15
      objective knowledge items, the median correlation between self-assessment and
      actual performance was 0.18. When the average self-assessment on the core
      competencies was correlated with the number of correct answers to the objective
      knowledge items, the correlation was 0.34. CONCLUSIONS: The modest sizes of the
      correlations suggest that workers are weak judges of what they know and do not
      know. To prepare public workers for emergency events, it is suggested that two
      steps are important: (1) using the core competencies, develop a local response
      plan, and (2) develop an objective knowledge test to assess workers' knowledge of
      the local response plan.

PMID- 15853455
TI  - Globalizing biosecurity.
AB  - A harmonized international regime that enhances biosecurity is needed to reduce
      the risk of bioterrorism. Like other security regimes, this will entail mutually
      reinforcing strands, which need to include: enactment of legally binding control
      of access to dangerous pathogens, transparency for sanctioned biodefense
      programs, technology transfer and assistance to developing countries to jointly
      advance biosafety and biosecurity, global awareness of the dual-use dilemma and
      the potential misuse of science by terrorists, and development of a global ethic
      of compliance. To work, this effort must be undertaken collectively, utilizing
      the international and regional institutions that already have a role to play in
      providing safety and security. Most notably, it must grow in a top-down manner
      from the Biological Weapons Convention accord, in which States Parties have
      agreed to ban the development of biological weapons, and in a bottom-up manner
      from the scientific and health communities, which are engaged in the research and
      public health efforts that must be protected against misuse-especially involving
      the World Health Organization.

PMID- 15853454
TI  - Automated screening for biological weapons in homeland defense.
AB  - Biological threat detection programs that collect air samples and monitor for
      large-scale release of biowarfare agents generate large numbers of samples that
      must be quickly and accurately screened for the presence of biological agents. An
      impediment to the rapid analysis of large numbers of environmental biological
      samples is that manual laboratory processes are time-consuming and require
      resources to maintain infrastructure, trained personnel, and adequate supplies of
      testing reagents. An ideal screening system would be capable of processing
      multiple samples rapidly, cost-effectively, and with minimal personnel. In the
      present study, we evaluated the Automated Biological Agent Testing System (ABATS)
      to explore the capability of automation to increase sample throughput, maximize
      system accuracy, and reduce the analysis costs associated with biological threat
      agent screening in environmental samples. This study demonstrates the utility of
      this concept and the potential of an automated system to address the growing
      environmental monitoring needs of the United States.

PMID- 15853456
TI  - Pandemic influenza preparedness in Maryland: improving readiness through a
      tabletop exercise.
AB  - In February 1999, the Maryland Department of Health and Mental Hygiene initiated
      pandemic influenza planning for the state of Maryland. This process involved
      several major steps, including the development of the Maryland Pandemic Influenza
      Preparedness Plan, and culminated in a high-level tabletop exercise to test the
      plan in April 2004. During the tabletop exercise, participants were presented
      with nine different fictitious scripts encompassing a single scenario. They were
      asked to respond to the information presented in each script, discuss
      organization-specific questions posed by the exercise facilitator, and make
      decisions regarding action steps that their organization would take in response
      to the various issues raised. The exercise identified a number of important gaps
      that need to be addressed, including (1) additional surge capacity specific to a
      pandemic, (2) greater understanding of the realities and implications of pandemic
      influenza among elected officials and decision-makers, (3) coordination of
      pandemic influenza planning with the existing emergency response infrastructure
      coupled with additional training in incident command, (4) further steps to
      operationalize several aspects of the Maryland Pandemic Influenza Preparedness
      Plan, and (5) additional federal guidance.

PMID- 15853457
TI  - The threat of pandemic influenza: are we ready?

PMID- 15853460
TI  - An adult rat spinal cord contusion model of sensory axon degeneration: the estrus
      cycle or a preconditioning lesion do not affect outcome.
AB  - A therapeutic strategy for acute spinal cord injury would be to reduce the
      progressive degeneration and disconnection of axons from their targets. Here, we
      describe a model to evaluate degeneration of the ascending sensory projections to
      the nuclei in the medulla following graded spinal cord contusions in adult female
      Sprague-Dawley rats. Cholera toxin B (CTB) labeling from the sciatic nerve of
      naive rats revealed effective labeling of the terminal fibers in the gracile
      nucleus at 3 days post-injection and a subpopulation of rapidly transporting
      fibers after 1 day. Seven days after contusions using the Infinite Horizon
      impactor the area of CTB-labeled terminal fibers had a negative correlation with
      increasing impact force. Moderate spinal contusions of around 150 kilodyne (kdyn
      or 0.15 x 10(-3) newton) caused a reduction to 40% in the fiber area which will
      enable the identification of protective as well as detrimental drugs and post
      injury mechanisms. A preconditioning injury of the sciatic nerve reportedly can
      enhance growth of sensory axons but did not affect the terminal fiber area in the
      gracile nucleus. Estrogen and progesterone are protective in various systems and
      could therefore influence experimental outcomes when using females. However, the
      phase of the estrus cycle at the time of contusion or during the post-injury time
      did not affect the outcome of the contusion, indicating that female rats may be
      used without consideration of the estrus cycle. This model can readily be used to
      evaluate pharmacological agents for protection of sensory axons and
      pathophysiological mechanisms of their degeneration.

PMID- 15853461
TI  - Telemetric monitoring of corpus spongiosum penis pressure in conscious rats for
      assessment of micturition and sexual function following spinal cord contusion
      injury.
AB  - Disruption of bladder function and sexual reflexes are major complications
      following spinal cord injury (SCI). We examined the use of telemetric monitoring
      of corpus spongiosum penis (CSP) pressures for assessment of micturition and
      erectile events following SCI in rats. Pressure catheters were implanted in the
      bulb of the CSP of seven male Long-Evans hooded rats, subjected to a standardized
      weight drop SCI (10 g x 12.5 mm) at T10. CSP pressures were analyzed for
      spontaneously occurring micturition and erectile events, and during ex copula
      reflex erection tests until 25 days after SCI. Urine volume was determined until
      21 days after SCI. Results show initial loss of bladder function after SCI with
      gradual return of reflex micturition. When compared to baseline (BL), micturition
      pressure characteristics after SCI included prolonged duration, increased area
      under the curve (AUC), increased mean pressures, increased number of pressure
      peaks, and increased peak frequency. At 21 days after SCI, the urine volume per
      micturition was significantly increased. The number of full erectile events
      decreased significantly following SCI. Pressure wave analyses demonstrated
      increased AUC, increased maximum pressures, increased suprasystolic peak
      duration, increased AUC of the suprasystolic peaks, and increased maximum
      pressures of the suprasystolic peaks during recovery. The number of partial
      erectile events decreased significantly following SCI. Ex copula reflex erection
      testing demonstrated significantly decreased latency. The study demonstrates that
      telemetric monitoring of CSP pressures in conscious rats is a valuable and
      reliable method for assessing recovery of autonomic function following SCI.

PMID- 15853462
TI  - Neuromechanical control of locomotion in the rat.
AB  - Rodent models are being extensively used to investigate the effects of traumatic
      injury and develop and assess the mechanisms of repair and regeneration. We
      present quantitative assessment of two-dimensional (2D) kinematics of overground
      walking and for the first time three-dimensional (3D) joint angle kinematics of
      all four limbs during treadmill walking in intact adult female Long-Evans rats.
      Gait cycle with subphases and intralimb and interlimb cyclograms are presented.
      Phase relationships between joint angles on a cycle-by-cycle basis and interlimb
      footfalls are assessed using a simple technique. Electromyogram (EMG) data from
      major flexor and extensor muscles for each of the hindlimb joints and elbow
      extensor muscles of the forelimbs synchronized to the 3D kinematics are also
      obtained. Overground walking kinematics, provides information on base of support,
      stride length, and hindfoot rotation. Treadmill walking kinematics indicate
      primarily monophasic angle trajectories for the hip and shoulder joints, weak
      double peak patterns for the knee and elbow joints, and a prominent double peak
      pattern for the ankle joints. Maximum flexion of the knee during swing precedes
      that of the ankle, which precedes that of the hip. A mild exercise regimen over 8
      weeks does not alter the kinematics. EMG activity indicates specific
      relationships of the neural activity to joint angle kinematics. We find that the
      ankle flexors as well as the hip and elbow extensors maintain constant burst
      duration with changing cycle duration. Data and techniques described here are
      likely to be useful for quantitative assessment of altered gait and neural
      control mechanisms after neurotrauma.

PMID- 15853463
TI  - Whiplash-associated disorders impairment rating: neck disability index score
      according to severity of MRI findings of ligaments and membranes in the upper
      cervical spine.
AB  - The aim of this study was to explore whether reported pain and functional
      disability in whiplash-associated disorders (WAD) patients is associated with
      lesions to specific soft tissue structures in the upper cervical spine, as
      assessed by MRI. Pre-selected structures for MRI assessment included the alar
      ligaments, the transverse ligament, the tectorial and the posterior atlanto
      occipital membranes. The questionnaire employed was a modification of the
      Oswestry Low Back Pain Index. It was comprised of ten single items related to
      pain and activity of daily living. Ninety-two whiplash patients and 30 control
      persons, randomly drawn, were included. WAD patients reported significantly more
      pain and functional disability than the controls, both for total score and each
      of the ten single items. In the WAD patients, MRI lesions to the alar ligaments
      showed the most consistent association to the reported pain and disability.
      Lesions to other structures often occurred in combination with lesions to the
      alar ligaments. Lesions to the transverse ligament and to the posterior atlanto
      occipital membrane also appeared to be related to the NDI score, although the
      association was weaker than for the alar ligament. The disability score increased
      with increasing number of abnormal (grade 2-3) structures. These results indicate
      that symptoms and complaints among WAD patients can be linked with structural
      abnormalities in ligaments and membranes in the upper cervical spine, in
      particular the alar ligaments.

PMID- 15853464
TI  - A significant increase in both basal and maximal calcineurin activity following
      fluid percussion injury in the rat.
AB  - Calcineurin, a neuronally enriched, calcium-stimulated phosphatase, is an
      important modulator of many neuronal processes, including several that are
      physiologically related to the pathology of traumatic brain injury. This study
      examined the effects of moderate, central fluid percussion injury on the activity
      of this important neuronal enzyme. Animals were sacrificed at several time-points
      postinjury and cortical, hippocampal, and cerebellar homogenates were assayed for
      calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A
      significant brain injury-dependent increase was observed in both hippocampal and
      cortical homogenates under both basal and maximally-stimulated reaction
      conditions. This increase persisted 2-3 weeks post-injury. Brain injury did not
      alter substrate affinity, but did induce a significant increase in the apparent
      maximal dephosphorylation rate. Unlike the other brain regions, no change in
      calcineurin activity was observed in the cerebellum following brain injury. No
      brain region tested displayed a significant change in calcineurin enzyme levels
      as determined by Western blot, demonstrating that increased enzyme synthesis was
      not responsible for the observed increase in activity. The data support the
      conclusion that fluid percussion injury results in increased calcineurin activity
      in the rat forebrain. This increased activity has broad physiological
      implications, possibly resulting in altered cellular excitability or a greater
      likelihood of neuronal cell death.

PMID- 15853465
TI  - Traumatic injury activates protein kinase B/Akt in cultured astrocytes: role of
      extracellular ATP and P2 purinergic receptors.
AB  - Protein kinase B/Akt is a key signaling molecule that regulates cell survival,
      growth, and metabolism, and inhibits apoptosis. Traumatic brain injury (TBI)
      activates Akt, and Akt has been implicated in neuronal survival after TBI, but
      little is known about injury-induced Akt activation in astrocytes, cells that
      exhibit hypertrophic and hyperplastic responses to CNS injury. Here we have
      investigated the effect of mechanical strain on Akt activation in primary
      cultures of rat cortical astrocytes growing on deformable Silastic membranes.
      When astrocytes were subjected to mechanical strain (50 msec; 5-7.5 mm
      displacement), we observed an increase in phosphorylation of serine 473, a key
      indicator of Akt activation. Akt phosphorylation was increased at 3 min
      postinjury, was maximal from 5 to 10 min, and declined gradually thereafter. Akt
      activation was also dependent on the severity of the injury. Stretch-induced Akt
      phosphorylation was attenuated by blocking calcium influx and phosphoinositide 3
      kinase (PI3K), an upstream activator of Akt. In addition, we found that ATP is
      rapidly released after mechanical strain and that the P2 purinergic receptor
      antagonist iso-pyridoxal-5'-phosphate-6-azophenyl-2',5'disulfonate (PPADS)
      attenuated trauma-induced Akt activation. We conclude that mechanical strain
      causes activation of Akt in astrocytes via stimulation of P2 receptors. This
      suggests that P2 receptor/Akt signaling promotes astrocyte survival and growth,
      and this process may play a role in the generation of reactive gliosis after TBI.

PMID- 15853466
TI  - Expression of myelencephalon-specific protease after cryogenic lesioning of the
      rat parietal cortex.
AB  - The gene for myelencephalon-specific protease (MSP) is a member of the kallikrein
      gene family and in rats is expressed mainly in the central nervous system. Its
      function and alteration in brain injury have not yet been clarified. We examined
      the expression of MSP after cryogenic injury (CI) using in situ hybridization,
      immunohistochemistry, and Western blotting. Analysis of MSP mRNA by in situ
      hybridization revealed a higher level of expression around the cryogenic area
      than on the contralateral side at 2-7 days after CI, with peak expression
      occurring 7 days after CI. Immunohistochemical analysis demonstrated expression
      of MSP protein at 1 day after CI, in the same region in which MSP mRNA was
      observed, with peak expression again at 7 days after CI, in the area around the
      lesion. Double immunohistochemical labeling revealed that MSP was expressed
      mainly in oligodendrocytes. These results suggest that expression of MSP may be
      related to the turnover of myelin-associated proteins and extracellular matrix
      proteins after CI. The regulation of active MSP may be important in the
      physiological or pathological changes involved in remyelination or demyelination.

PMID- 15853467
TI  - Bipolar disorder: current clinical research trends.

PMID- 15853469
TI  - Stroke Society of Australasia annual scientific meeting. 13-16 September 2004,
      Hobart, Tasmania, Australia.

PMID- 15853470
TI  - Valdecoxib for the management of chronic and acute pain.
AB  - Cyclooxygenase-2 specific inhibitors have anti-inflammatory and analgesic
      properties, and are effective in managing a wide range of chronic and acute
      painful conditions such as adult rheumatoid arthritis, osteoarthritis, migraine,
      primary dysmenorrhea and postoperative pain. Valdecoxib, an orally administered
      cyclooxygenase-2 specific inhibitor, provides effective pain relief for both
      chronic and acute conditions, and reduces postoperative opioid use, with a
      concomitant reduction in opioid-related adverse events. Valdecoxib also has
      superior gastrointestinal safety compared with nonspecific nonsteroidal anti
      inflammatory drugs, and at therapeutic doses, it is generally safe and well
      tolerated in terms of renal and cardiovascular events. This drug profile reviews
      the efficacy, safety and tolerability of valdecoxib for the management of chronic
      and acute pain.

PMID- 15853471
TI  - Interferon-beta1a treatment for multiple sclerosis.
AB  - Although multiple sclerosis is probably the most common cause of neurologic
      disability in young adults, the cause is unknown, the prognosis uncertain and
      available treatments unsatisfactory. Multiple sclerosis is an inflammatory
      autoimmune disorder of the CNS and the result of both environmental factors and
      susceptibility genes. The prognosis is difficult or impossible to predict at the
      time of diagnosis. Treatments that modulate the course of the disease have only
      recently become available but the long-term aim to prevent disability and promote
      repair remains distant. Interferon-beta is the most widely used therapy. The
      efficacy of interferon-beta in the short term is well documented in many large
      treatment trials, but the treatment effects are only modest and many issues
      relating to efficacy in the long term are unresolved. These include uncertain
      benefit on conversion to secondary-progressive multiple sclerosis, the relevance
      of neutralizing antibodies and the controversial effect on multiple sclerosis
      related brain atrophy.

PMID- 15853472
TI  - Ropinirole in the treatment of restless legs syndrome.
AB  - Ropinirole is an original nonergoline dopamine agonist indicated for the
      treatment of Parkinson's disease. However, recent developments in the study of
      restless legs syndrome have demonstrated another role for this drug. The symptoms
      of restless legs syndrome are responsive to dopaminergic agents such as
      ropinirole. The dosage of ropinirole needed to treat the symptoms of restless
      legs syndrome appears to be much smaller than what is necessary for Parkinson's
      disease therapy. The liver is primarily responsible for the metabolism of
      ropinirole, which has an elimination half-life of approximately 6 h. Ropinirole
      is generally well tolerated, with no serious adverse effects. Clinical studies
      have indicated that ropinirole can effectively reduce the motor symptoms of
      restless legs syndrome and improve overall sleep quality.

PMID- 15853473
TI  - Eletriptan in migraine.
AB  - Migraine is a highly prevalent, chronic and disabling illness in which the gap
      between practice guideline recommendations and actual clinical practice remains
      wide. Eletriptan, similar to other triptans, is a potent 5-HT(1B/1D) receptor
      agonist with a high selectivity for cranial versus coronary artery constriction
      and favorable pharmacokinetic profile. An extensive program of double-blind,
      placebo-controlled, head-to-head comparator trials has demonstrated the superior
      efficacy of eletriptan compared with the combination of ergotamine and caffeine,
      and selected oral triptans for the acute treatment of migraine. Eletriptans
      tolerability profile makes it a good choice as a first-line treatment of
      migraine. An early treatment study suggests that treatment of mild headache is
      associated with unusually high sustained pain-free rates and a tolerability
      profile that is equivalent to placebo.

PMID- 15853474
TI  - Rofecoxib in migraine.
AB  - Migraine is a highly prevalent primary headache. The disability of migraine
      attacks results in considerable economic and social losses. The acute treatment
      of migraine aims to rapidly and consistently alleviate the head pain and
      associated symptoms, therefore reducing the headache-related disability, ideally
      without side effects and recurrence of the attack within 24 h. Although several
      drug options and different formulations are available, the choice of a specific
      medication should depend on an individual patients characteristics. Among the
      available drugs, nonsteroidal anti-inflammatory drugs still represent effective
      options and a new class of nonsteroidal anti-inflammatory drugs known as
      selective cyclooxygenase-2 inhibitors may represent an even better-tolerated
      therapy with regard to gastrointestinal side effects. This article aims to
      discuss the role of rofecoxib in the acute treatment of migraine. Although this
      drug was recently withdrawn from the market, it provides a good model to
      understand the role of the cyclooxygenase-2 inhibitors in migraine therapy
      overall. The pharmacologic profile and therapeutic use in the acute treatment of
      migraine of rofecoxib is reviewed. In addition, the limitations of a
      monotherapeutic orally administered approach and possible ways of raising the
      efficacy of rofecoxib and other acute migraine treatments are reviewed.

PMID- 15853475
TI  - Bipolar mixed states and their treatment.
AB  - Bipolar mixed states remain a nosologic dilemma, diagnostic challenge and
      neglected area of therapeutic research. While the outcome of mixed states is
      generally poorer than that of pure manic and depressive episodes, little is known
      about how to treat such a condition. The aim of this report is to investigate the
      results of clinical trials, including mixed bipolar patients, in order to provide
      some hints on the efficacy of the different compounds on this specific
      subpopulation. As a result of this research, it becomes clear that only dysphoric
      mania has been reasonably addressed in clinical trials, and unfortunately very
      little is known about the treatment of other mixed states. There is some indirect
      evidence that mixed mania may be more responsive to anticonvulsants than to
      lithium. Divalproate, and to a lesser extent carbamazepine, may be used either in
      monotherapy or as adjuncts to lithium. Use of other anticonvulsants, such as
      gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate or
      zonisamide is not yet supported by controlled data. The use of antidepressants is
      largely discouraged, as they may worsen this condition. On the other hand,
      atypical antipsychotics may be effective and safe either in monotherapy or in
      combination with lithium or valproate. Further research is urgently needed in
      this neglected area of psychiatry.

PMID- 15853476
TI  - Treatment of bipolar depression: focus on pharmacologic therapies.
AB  - Recent studies have highlighted significant limitations in our capacity to
      effectively treat bipolar depression. This article reviews the present status of
      treatments for this condition, highlighting emerging new pharmacotherapies such
      as lamotrigine, olanzapine and quetiapine, while also addressing modern
      psychologic interventions such as cognitive behavioral therapy and
      psychoeducation. The role of older treatments such as lithium and the
      antidepressants is also discussed, particularly as a recent meta-analysis has
      thrown into question current heightened concern over antidepressant-induced
      mania. The advent of new pharmacologic and psychologic treatments provides
      optimism for improved outcomes for this highly disabling condition.

PMID- 15853477
TI  - Executive dysfunction in major depressive disorder.
AB  - Executive dysfunction is commonly seen in major depression. The types of
      executive deficits seen in depression include problems with planning, initiating
      and completing goal-directed activities. Executive dysfunction may vary as a
      function of the severity of depression. In addition, a subset of geriatric
      depression is also characterized by prominent deficits in executive functioning.
      The presence of executive dysfunction in depression is associated with vocational
      disability and possibly poorer treatment response. While few studies have
      examined the treatment of executive dysfunction in depression, preliminary work
      suggests that both pharmacologic interventions and psychosocial interventions
      such as problem solving therapy may be efficacious.

PMID- 15853478
TI  - Neuropsychologic functioning and structural MRI of the brain in patients with
      schizophrenia.
AB  - The first episode of schizophrenia represents a transition from a premorbid to a
      morbid state. Studying the first episode of schizophrenia is useful since it is
      devoid of the confounds of chronicity and long-term medication. It is also likely
      to direct us to the core deficits of the illness. Studies on first-episode
      schizophrenia suggest a generalized neuropsychologic impairment, but that memory,
      attention and executive function are more severely impaired. Support for a
      neurodevelopmental model of neuropsychologic impairment in schizophrenia is
      derived from the findings that much of the neuropsychologic impairment is present
      by illness onset, that neuropsychologic impairment remains stable over time and
      that there is a weak relation between duration of untreated psychosis and
      neuropsychologic impairment. However, neuropsychologic impairment is moderated by
      neuroleptic treatment, with some evidence that atypical antipsychotics may have
      some beneficial effects over conventional antipsychotics. The causal mechanisms
      of brain abnormality in the temporal and frontal lobes appear to be different to
      that of neuropsychologic impairment in schizophrenia. The observation that there
      is a brain volume decrement over time and that the rate of change is higher
      during the first 5 years would be consistent with a neurodegenerative model of
      schizophrenia. At the same time, the basal ganglia are vulnerable to volumetric
      increase secondary to neuroleptic medication. Understanding the roles of the
      neurodevelopmental and neurodegenerative models of schizophrenia is important in
      deciding intervention strategies.

PMID- 15853479
TI  - Suicidal behavior in schizophrenia.
AB  - There is a high prevalence of suicidal behavior in individuals suffering from
      schizophrenia and recent investigations substantially elucidate this problem and
      provide useful insights about clinical risk factors, neurobiologic underpinnings
      and the impact of various treatments on reducing such behavior. The risk of
      suicide is greatest early in the course of schizophrenic illness but continues
      throughout life; risk factors for suicidal behavior include psychosis, depression
      and substance abuse. Effectively treating positive symptoms and depression,
      reducing substance abuse, avoiding akathisia, addressing demoralization and
      instilling hope are important elements in this treatment approach. The newer
      generation of atypical antipsychotics (particularly clozapine) and new
      psychologic approaches (particularly cognitive behavioral therapy) appear to be
      useful in reducing suicidality in schizophrenia. The significant advances in
      defining the neurobiologic basis of suicidality may enable the development of
      more effective treatments. The renewed emphasis on resilience and recovery as
      desired outcomes in schizophrenia and the accompanying sense of hope encourage
      optimism about effectively reducing suicidality in schizophrenia. Over the past
      10 years, much has been learnt and hopefully this momentum will be translated
      into increasingly better outcomes.

PMID- 15853480
TI  - Butyrylcholinesterase: impact on symptoms and progression of cognitive
      impairment.
AB  - The most successful approach for treating people with Alzheimer's disease to date
      has been by improving cholinergic transmission using cholinesterase inhibitors.
      Many of these drugs selectively inhibit acetylcholinesterase but some agents
      inhibit both acetylcholinesterase and butyrylcholinesterase. Recent evidence from
      studies examining butyrylcholinesterase in post mortem brain samples from
      dementia patients and examining the relationship between butyrylcholinesterase
      polymorphisms and the progression of cognitive impairment in dementia with Lewy
      bodies and Alzheimer's disease add to a body of work suggesting that
      butyrylcholinesterase is present in key brain areas and may influence the
      maturation of plaques in Alzheimer's disease. These accumulating data suggest
      that butyrylcholinesterase contributes to disease progression in people with
      dementia, which may be particularly important in individuals with more severe
      dementia as butyrylcholinesterase activity increases with disease development. It
      is a priority for future clinical trials to determine whether agents which
      inhibit butyrylcholinesterase and acetylcholinesterase have a greater clinical
      efficacy.

PMID- 15853481
TI  - Treatment of attention deficit hyperactivity disorder in adults.
AB  - A number of medication and psychologic treatment options for adults with
      attention deficit hyperactivity disorder have become available during the past 5
      years, while others are under investigation. This review describes the safety and
      effectiveness of the stimulants (i.e., methylphenidate and dexedrine), and
      particularly the newer long-acting stimulants (i.e., Concerta) and Adderall XR)
      in the treatment of this population. Some nonstimulant/nonantidepressants,
      particularly atomoxetine, have also been shown to improve attention deficit
      hyperactivity disorder symptoms. Combination treatment of stimulants and
      antidepressants require more study with regard to safety and efficacy.
      Psychosocial interventions (e.g., cognitive behavioral therapy, mindfulness
      training and cognitive remediation) can also benefit adults with attention
      deficit hyperactivity disorder. Cognitive behavioral therapy combined with
      medication is more effective than either intervention alone, especially for
      addressing the emotional and functional aspects of peoples lives and thus
      improving occupational, interpersonal and emotional outcomes.

PMID- 15853482
TI  - Aromatase inhibitors as add-on treatment for men with epilepsy.
AB  - Manipulation of neurosteroids to treat epilepsy has been an area of active
      research. The effect of testosterone on brain excitability and seizure threshold
      has been mixed; the estradiol metabolite of testosterone increases brain
      excitability, while the reduced metabolite of testosterone, 3alpha
      androstanediol, decreases brain excitability, likely through an action at the
      gamma-amino butyric acid A receptor. Therefore, the metabolites of testosterone
      produce opposite effects on brain excitability in seizure models. Aromatase is
      the enzyme for the conversion of testosterone to 17beta-estradiol. Aromatase
      inhibitors could decrease brain excitability by decreasing local estradiol levels
      and therefore, could be beneficial for the treatment of epilepsy. Aromatase
      inhibitors are US Food and Drug Administration-approved and have a long history
      of safe use in menopausal women with breast cancer. This review presents the
      results of using anastrazole in an open-label, add-on manner in a small group of
      men with epilepsy in order to improve seizures. The results suggested some effect
      on reduction of seizures and no side effects. Testosterone levels did increase,
      but not to above the normal range. Letrozole used in a single case was also
      beneficial for seizures. It was concluded that aromatase inhibitors may be a
      useful adjunct to the treatment of epilepsy, but habituation to the treatment may
      be limiting. Many men with epilepsy have low testosterone, and aromatase
      inhibition may be helpful in restoring levels to normal. Modulation of
      reproductive hormones by aromatase inhibition as well as enhancement of the
      3alpha-androstanediol pathway may be an avenue of epilepsy treatment that would
      not produce sedative side effects, which is often a limiting factor with standard
      antiseizure medications. A further interesting result is that elevated follicle
      stimulating hormone and luteal stimulating hormone levels were associated with
      seizure reduction, suggesting that they may be a biomarker for a beneficial
      effect of aromatase inhibition on brain excitability.

PMID- 15853483
TI  - Pharmacotherapy of post-traumatic stress disorder: a family practitioners guide
      to management of the disease.
AB  - Post-traumatic stress disorder is a difficult to treat, yet common disorder,
      which is associated with significant morbidity, mortality and societal burden.
      Comprehensive management of post-traumatic stress disorder must include both
      psychotherapeutic and pharmacologic components. The current evidence-based
      pharmacologic management approaches to post-traumatic stress disorder, suggests
      that first-line treatments for monotherapy are the selective serotonin reuptake
      inhibitors, sertraline, paroxetine and fluoxetine. Other potential options
      include other monotherapies including venlafaxine, mirtazapine, tricyclic
      antidepressants, monoamine oxidase inhibitors, as well as adjunctive usage of
      atypical antipsychotics, lamotrigine, trazadone and a number of adrenergic
      agents. A trial of therapy should be at least 8 weeks and continue for at the
      very least 12 months, but is likely to be much longer. In light of the risks of
      untreated post-traumatic stress disorder (e.g., suicide and impaired psychosocial
      functioning), therapy may need to be continued for 2 years or more. Pharmacologic
      therapy instituted at the time of acute psychologic trauma shows promise for the
      prevention of post-traumatic stress disorder in the future and warrants further
      study.

PMID- 15853484
TI  - Combining therapies for the treatment of migraine: is there a role?

PMID- 15853486
TI  - Interferon-beta1b for multiple sclerosis.
AB  - Interferon-beta1b (Betaseron/Betaferon) was the first approved therapy for
      relapsing-remitting multiple sclerosis. The US Food and Drug Administration has
      expanded the indication to include relapsing forms of multiple sclerosis which
      encompasses secondary-progressive multiple sclerosis if relapses are present. In
      one scientifically sound head-to-head comparison (Independent Comparison of
      Interferon trial), interferon-beta1b was shown to be clinically superior to low
      dose interferon-beta1a (Avonex). Current studies are underway to compare it with
      a double dosage of interferon-beta1b [corrected] as well as glatiramer acetate.
      Neutralizing antibodies are more likely to occur with interferon-beta1b, but
      their clinical significance has shown conflicting and confusing results making
      the utility of measuring neutralizing antibodies uncertain. Up to 12 years of
      follow-up data suggest that the drug remains effective on T2 magnetic resonance
      imaging burden of disease in those who stay on therapy. Initially, the major
      problem with interferon-beta1b was a lack of tolerability due to high incidents
      of skin reactions and influenza-like side effects. Patient adherence has improved
      dramatically with the introduction of autoinjectors and protocol changes
      including initial dose escalation, prophylactic ibuprofen or acetaminophen,
      evening administration of drug and an attentive nurse support system. Interferon
      beta1b remains a first-line treatment for relapsing-remitting multiple sclerosis
      and relapsing forms of secondary-progressive multiple sclerosis based on robust
      efficacy data and a long-term safety profile.

PMID- 15853487
TI  - Divalproex sodium in the treatment of pediatric psychiatric disorders.
AB  - Divalproex sodium is an anticonvulsant that is used extensively in adults with
      indications for epilepsy, acute mania and migraine prophylaxis. It has been used
      in children and adolescents as a first-line agent for mania in bipolar disorder.
      Its efficacy as a mood stabilizer has been established, and there have been
      studies outlining its efficacy as an agent effective in the treatment of conduct
      disorder, disruptive behavior disorders, aggression and explosive disorder.
      Longer-acting formulations are now available that cause less gastrointestinal
      side effects and can also be taken once a day, thus potentially increasing
      adherence, an important factor in this patient population. Future directions
      would include developing a more potent valproic acid formulation with fewer side
      effects, completing randomized controlled trials to establish the efficacy of
      divalproex sodium in various other pediatric psychiatric disorders, establishing
      the relative efficacy of the compound in head-to-head comparisons with other mood
      stabilizers, examining systematically the value of the compound in multimodal
      pediatric psychiatric treatment packages, and complete effectiveness trials that
      demonstrate the short- and long-term effectiveness of the compound in the real
      world of clinicians. In this drug profile, divalproex sodium and its uses in the
      pediatric population for psychiatric conditions are reviewed.

PMID- 15853488
TI  - Risperidone for bipolar disorders.
AB  - Atypical antipsychotic medications are a relatively new, increasingly prominent
      component of the treatment armamentarium for bipolar disorder -- a development
      that provides more options for potentially improved outcomes for patients and
      families affected by bipolar disorder. The US Food and Drug Administration
      approved bipolar indications for risperidone include monotherapy for the short
      term treatment of acute manic or mixed episodes associated with bipolar I
      disorder and combination therapy with lithium or valproate for the short-term
      treatment of acute manic or mixed episodes associated with bipolar I disorder.
      Risperidone is also approved in over 30 countries worldwide for bipolar mania
      either as monotherapy, adjunct therapy, or both monotherapy and adjunct therapy.
      A number of controlled and open-label treatment trials have shown risperidone's
      efficacy and tolerability in the manic phase of bipolar disorder. Risperidone has
      also been reported to be useful in the longer-term treatment of bipolar disorder.
      This drug profile of risperidone for bipolar disorder will address the chemistry,
      pharmacodynamics, pharmacokinetics and metabolism of risperidone, clinical trials
      in bipolar disorder, postmarketing surveillance, safety, tolerability and
      regulatory issues. Finally, a discussion of potential future directions, a
      summary of key issues and information resources are provided.

PMID- 15853489
TI  - Advances in revascularization for acute ischemic stroke treatment.
AB  - Intravenous thrombolysis with recombinant tissue plasminogen activator is the
      established treatment for acute ischemic stroke patients presenting within 3 h
      after stroke onset. In a significant number of patients, however, intravenous
      thrombolysis with recombinant tissue plasminogen activator remains ineffective.
      New thrombolytic agents, such as reteplase, tenecteplase or desmoteplase, offer
      pharmacokinetic and dynamic advantages over recombinant tissue plasminogen
      activator and have been or are currently being tested for safety and efficacy in
      clinical trials. Endovascular revascularization is an evolving treatment option
      enabling mechanical clot disruption or extraction in combination with
      thrombolysis. Several new endovascular devices have been successfully tested for
      safety in acute ischemic stroke patients and are now being tested for efficacy in
      larger clinical trials. Continued innovation and refinement of endovascular
      technology and techniques is expected to increase technical success with a
      minimal procedure-related morbidity in the treatment of acute ischemic stroke.

PMID- 15853490
TI  - The need for emergency treatment of transient ischemic attack and minor stroke.
AB  - The risk of recurrent stroke following transient ischemic attack or minor stroke
      has recently been shown to be 5-10% at 1 week and 10-20% at 3 months, depending
      on study population and methods. This is considerably higher than previously
      estimated and current clinical guidelines reflect the need for rapid assessment
      although a wide variation in practice exists. Effective management of patients
      with transient ischemic attack or minor stroke, therefore, requires
      identification of individuals at the highest (and lowest) risk and initiation of
      appropriate secondary prevention. Risk can be stratified at initial presentation
      by the presence or absence of simple clinical features and following subsequent
      investigation. For transient ischemic attack patients, older age, diabetes,
      longer duration of symptoms and weakness or speech disturbance identify patients
      at highest risk, as does the presence of large artery atherosclerosis (mainly
      internal carotid artery stenosis) and lesions on diffusion-weighted magnetic
      resonance imaging. Strong evidence exists for the benefit of some early
      interventions (carotid endarterectomy and antiplatelet agents), but is
      circumstantial or awaited for others (statins and antihypertensives). In order
      for the public health challenge posed by transient ischemic attack and minor
      stroke to be met, considerable change is required in both public education (to
      ensure correct recognition of symptoms and swift presentation to medical
      attention) and the provision of clinical services to ensure the timely initiation
      of effective treatment.

PMID- 15853491
TI  - Treatment with statins in the acute phase of ischemic stroke.
AB  - Although statins are being used for the secondary prevention of ischemic stroke,
      recent experimental data have shown new pleiotropic effects of these drugs
      independent of their lipid-lowering properties that might be responsible for
      their role in neuroprotection. In fact, statins have been successfully tested in
      animal models of acute cerebral ischemia. In humans, the possibility that statins
      could be used for the treatment of acute ischemic stroke has not yet been
      addressed, however, a pilot trial and observational studies testing this approach
      showed promising results for a disease in which tissue plasminogen activator is
      the only available treatment for a reduced number of patients. The aim of this
      review is to answer the basic question of whether treatment with statins
      initiated in the acute phase of ischemic stroke is feasible and if it can improve
      neurologic outcome. The possible benefits of this scenario will be discussed.

PMID- 15853492
TI  - Thrombolytic therapy for acute ischemic stroke: 3 h and beyond.
AB  - The current status of thrombolytic therapy approved by the US Food and Drug
      Administration is intravenous recombinant plasminogen activator given within 3 h
      of the onset of ischemic stroke. Intra-arterial therapy is possible for up to 6 h
      but is not Food and Drug Administration-approved for this purpose. Based on
      current radiologic methods (i.e., magnetic resonance imaging and perfusion
      computed tomography scans), it is being increasingly realized that the time
      window for effective thrombolytic therapy is variable, and salvageable tissue in
      the form of the ischemic penumbra may exist for longer periods of time and could
      therefore offer a greater time window based on these imaging studies. Development
      of an effective neuroprotective drug would greatly enhance the stability of the
      penumbra and offer further opportunities for extending the time window for
      reperfusion.

PMID- 15853493
TI  - Therapeutic hypothermia for stroke: do new outfits change an old friend?
AB  - Clinically significant neuroprotection for the brain continues to be an elusive
      quest. All attempts at developing effective pharmacologic agents have failed in
      clinical trials. Hypothermia has been thought to confer protection after brain
      injury for many years, but has recently regained interest as a neuroprotectant
      for focal ischemic stroke in the basic science and clinical literature. The
      failure to develop safe and efficacious pharmacologic agents along with promising
      clinical data on the efficacy of hypothermia for cardiac arrest patients have
      raised a great interest in hypothermia as a neuroprotectant for ischemic stroke.
      As a clinically meaningful neuroprotectant for stroke, hypothermia confers
      several theoretical advantages over pharmacologic agents. A major problem with
      neuroprotectant therapy is instituting therapy within a narrow time window. This
      obstacle may be easier for hypothermia to overcome as emergency medical service
      personnel can theoretically initiate it in the field. Additionally, pharmacologic
      agents are usually restricted to one aspect of the pathophysiologic cascade
      triggered by focal ischemia, whereas hypothermia acts on several of these
      pathways simultaneously. The recent advances and future directions in the
      utilization of hypothermia as a potential therapy for focal ischemic stroke are
      reviewed.

PMID- 15853494
TI  - Cognitive behavioral psychotherapy for generalized anxiety disorder: a primer.
AB  - Generalized anxiety disorder is a highly debilitating psychologic disorder
      associated with cognitive, affective, behavioral and physiologic forms of
      rigidity and dysfunction. Chronic and uncontrollable worry, a future-oriented and
      highly negative form of verbal thought, is its hallmark symptom. Cognitive
      behavioral therapy, the most well-established psychologic treatment for
      generalized anxiety disorder, entails techniques designed to target and reduce
      dysfunction in each of these mutually interrelating domains. This review serves
      as an introduction to cognitive behavioral therapy for generalized anxiety
      disorder, including conceptualization, treatment methods and evidence for
      efficacy. Future directions for augmenting treatment efficacy are also discussed.

PMID- 15853495
TI  - Management of panic disorder.
AB  - Selective serotonin reuptake inhibitors are the first-line treatment for panic
      disorder. They are effective and well tolerated. Although tricyclic
      antidepressants are equally effective, they are less well tolerated than the
      selective serotonin reuptake inhibitors. Monoamine oxidase inhibitors can be
      efficacious but have a range of unwanted effects that preclude their use as first
      line treatments. Benzodiazepines should be reserved for short-term use and for
      treatment-resistant patients who do not have a history of dependence and
      tolerance. Also, they can be combined with selective serotonin reuptake
      inhibitors in the first weeks of treatment to tide the patient over before the
      onset of the response. Cognitive behavioral therapy is the psychologic treatment
      of first choice. The methods of combining drug and nondrug treatments need
      careful and thorough exploration.

PMID- 15853496
TI  - Emerging roles for atypical antipsychotics in chronic post-traumatic stress
      disorder.
AB  - Post-traumatic stress disorder is an anxiety disorder that may occur after the
      individual is exposed to severe psychologic trauma such as combat, sexual
      assault, or childhood physical or sexual abuse. Chronic post-traumatic stress
      disorder may result in considerable psychologic pain and suffering for the
      individual in addition to significant functional impairment. In addition to the
      heterogeneity of symptoms that occur in post-traumatic stress disorder, there may
      also be extensive comorbidity with other anxiety disorders, mood disorders,
      psychotic disorders, and other psychiatric disorders. This complicates the
      treatment picture. Currently, accepted treatments for post-traumatic stress
      disorder include psychotherapy, in particular cognitive behavioral-based
      approaches and antidepressant medication. However, many patients are refractory
      to these initial treatments or have only a partial response. In light of this,
      may clinicians combine additional classes of psychotropic agents and different
      psychotherapeutic approaches to enhance treatment response. This article reviews
      the literature on the use of atypical antipsychotics in the treatment of post
      traumatic stress disorder. Most of the research to date has involved combat
      veterans partially responsive or refractory to treatment, namely with
      antidepressants. Studies have shown improvement across post-traumatic stress
      disorder symptom clusters, as well as improvement in comorbid psychotic symptoms
      or disorders. More research is needed to confirm these recent findings and
      further delineate the role of atypical antipsychotics in the treatment of post
      traumatic stress disorder. Currently, possible indications for their use include
      treatment-resistant post-traumatic stress disorder and post-traumatic stress
      disorder with comorbid psychotic features.

PMID- 15853497
TI  - Acetylcholinergic neurotransmission and the beta-amyloid cascade: implications
      for Alzheimer's disease.
AB  - Alzheimer's disease is characterized by both decreases in acetylcholinergic
      neurotransmission and increases in beta-amyloid accumulation. Currently,
      available clinical psychopharmacologic treatment is focused on increasing
      acetylcholinergic neurotransmission, whereas no clinical treatments to directly
      reduce beta-amyloid accumulation are available. Cholinesterase inhibitors improve
      cognition, certain neuropsychiatric symptoms and functional impairment in
      patients with mild-to-moderate Alzheimer's disease, and it is believed that this
      is mainly symptomatic treatment. However, this review discusses various levels of
      interaction between acetylcholinergic neurotransmission and the beta-amyloid
      cascade, which suggest that some specific acetylcholinergic treatments may reduce
      beta-amyloid accumulation, and therefore may slow disease progression over the
      long term. Various suggestions are made on how such potential disease-modifying
      effects could be studied in the future.

PMID- 15853499
TI  - Dementia: molecules, measures and methods.

PMID- 15853501
TI  - CNS diseases congress: advances in therapeutics, tools and trials. 28-29 June
      2004, Strategic Research Institute, Philadelphia, PA, USA.

PMID- 15853502
TI  - Uses of topiramate in the treatment of alcohol dependence.
AB  - Alcohol dependence is a major cause of morbidity and mortality in the USA and
      throughout the world. Over the last 10 years there has been an intense interest
      in developing pharmacotherapies that address the neurochemistry of alcohol
      dependence. Using a novel pharmacological approach to treating alcohol
      dependence, topiramate (Topamax, Ortho-McNeil Pharmaceutical) has recently been
      shown to improve the drinking outcomes of alcohol-dependent individuals. This
      drug profile highlights the scientific concepts and clinical evidence in the
      development of topiramate for treating alcohol dependence.

PMID- 15853503
TI  - Use of olanzapine in the treatment of bipolar I disorder.
AB  - Olanzapine (Zyprexa, Eli Lilly & Co.) is an atypical antipsychotic medication
      with once-daily dosing that was originally developed for the treatment of
      schizophrenia. It has shown broad efficacy in the treatment of bipolar mixed and
      manic episodes, but is less effective in the treatment of bipolar depression.
      Double-blind studies have demonstrated a rapid onset of action in acute bipolar
      mania, significantly greater rates of response compared with placebo, and a
      remission rate of 88.3% in a 49-week open-label study. Diverse presentations of
      the illness responded well to olanzapine including patients with rapid-cycling
      bipolar disorder, mixed episodes, as well as psychotic and nonpsychotic manias.
      Olanzapine monotherapy improved symptoms of depression related to its sedating
      and appetite-enhancing profile, but core symptoms such as depressed mood did not
      improve significantly. However, in combination with fluoxetine, bipolar depressed
      patients responded without an increased risk of mania. Weight gain and sedation
      are prominent adverse effects, and it has been associated with atherogenic
      dyslipidemia and glucose intolerance.

PMID- 15853504
TI  - Escitalopram: better treatment for depression is through the looking glass.
AB  - Depression remains a common and often devastating illness. With the introduction
      of the selective serotonin reuptake inhibitors in the 1980s, patients were
      afforded treatment for depression that was both safer and better tolerated than
      any prior treatment modality offered. Although selective serotonin reuptake
      inhibitors quickly became the most widely used medications for the treatment of
      depression, no single agent has been recognized as an obvious first-line choice.
      Chirality potentially offers one method to improve upon the selective serotonin
      reuptake inhibitor class. For racemic compounds that differ in stereospecificity,
      separation into single enantiomers can result in significant changes in potency,
      tolerability and efficacy. One of the most widely prescribed selective serotonin
      reuptake inhibitors is citalopram, which exists as a racemic mixture of R- and S
      enantiomers. The S-enantiomer escitalopram (Cipralex, Lundbeck) is the
      therapeutically active portion of the parent compound and has a proven
      antidepressant efficacy. The R-enantiomer lacks activity as an antidepressant and
      has been shown to inhibit the effect of the S-enantiomer when the two are
      combined. Escitalopram is the most selective member of its class and with minimal
      effects on the cytochrome P450 system, has a negligible potential for drug-drug
      interactions. In placebo-controlled trials, escitalopram has consistently
      demonstrated symptomatic improvement as early as the first to second week of
      treatment. In addition to antidepressant efficacy, escitalopram also appears to
      exhibit significant anxiolytic properties. It has also shown efficacy in treating
      panic disorder and generalized and social anxiety disorders. This is advantageous
      as many patients who suffer from depression also experience comorbid anxiety
      disorders.

PMID- 15853505
TI  - Ropivacaine: a pharmacological review.
AB  - Ropivacaine (Naropin, AstraZeneca) a new long-acting amide local anaesthetic
      agent, is a pure S-enantiomer, with a high pKa and relatively low-lipid
      solubility. Since its clinical introduction in 1996, it has been the focus of
      intense interest because of its increased CNS and cardiovascular safety compared
      with bupivacaine. This article reviews the pharmacology of ropivacaine with
      particular emphasis placed on toxicological issues. Compared with bupivacaine
      (the drug of choice for many years), ropivacaine is equally effective for
      subcutaneous infiltration, epidural, intrathecal and peripheral nerve block
      surgery, and obstetrics and postoperative analgesia. Ropivacaine is virtually
      identical to bupivacaine in terms of onset, quality and duration of sensory
      block, but seems to produce less motor block. The lesser toxicity of ropivacaine
      compared with bupivacaine has been confirmed in numerous animal experiments as
      well as human studies, including studies considering the presumed lower potency
      of ropivacaine. In fact, the reduced cardiovascular toxicity compared with
      bupivacaine may be a distinct feature of ropivacaine. So far, the increased cost
      of ropivacaine compared with bupivacaine has limited its wider clinical use -- in
      spite of the improved safety profile. During the last few years, cost differences
      between bupivacaine and ropivacaine have been minimized, thus making
      pharmacoeconomical speculations a much lesser concern when choosing a local
      anaesthetic drug. In conclusion, ropivacaine appears to be a safer local
      anaesthetic agent than bupivacaine. It seems particularly indicated for major
      peripheral nerve blocks and obstetrics. Ropivacaine should be considered when
      regional blocks are used in neonates and young infants. With the current trend in
      the cost development, ropivacaine will most likely be used increasingly in the
      future.

PMID- 15853506
TI  - Inflammatory processes and Alzheimer's disease.
AB  - The inflammatory hypothesis of Alzheimer's disease, which states that anti
      inflammatory drugs could have beneficial effects on the pathophysiology of
      Alzheimer's disease, has been extensively investigated in clinical,
      epidemiological and basic research studies over the last 20 years. However,
      despite much hope, the hypothesis remains unproven. Although the results from the
      first small clinical trial with an anti-inflammatory agent in Alzheimer's disease
      appeared promising, subsequent trials with a variety of anti-inflammatory agents
      have failed to show beneficial effects. There are many potential reasons for this
      including drug selection, drug dose, timing and duration of treatment. This
      article reviews evidence in support of the inflammatory hypothesis in Alzheimer's
      disease, as well as the progress of clinical trials using specific anti
      inflammatory treatment regimens. It is concluded that such treatments should not
      be recommended, although additional investigation is warranted.

PMID- 15853507
TI  - Utilizing combination therapy in the treatment of Alzheimer's disease.
AB  - Alzheimer's disease may not yet be curable, but it is treatable. Two classes of
      drugs with differing mechanisms of action have received Food and Drug
      Administration approval for the treatment of Alzheimer's disease: the
      cholinesterase inhibitors and the N-methyl-D-aspartate receptor antagonist
      memantine (Ebixa, Lundbeck; Namenda, Forest Laboratories). Alzheimer's disease
      research directed at increasing the understanding of the underlying disease
      process has led to the identification of several other potential targets for drug
      development strategies. Due to the complexity of the disease, it is possible that
      combination therapy -- concomitant use of agents with nonoverlapping or even
      synergistic mechanisms of action -- may represent the best means available to
      enhance treatment effectiveness. This review evaluates the available data on
      combination therapy in Alzheimer's disease and provides an expert opinion on the
      use and implementation of combination therapy in clinical practice.

PMID- 15853508
TI  - Nonpharmacological and pharmacological interventions for symptoms in Alzheimer's
      disease.
AB  - Patients with Alzheimer's disease may suffer from noncognitive symptoms as well
      as cognitive symptoms, which the condition is better known for. Behavioral and
      psychiatric symptoms are common in patients with Alzheimer's disease and may
      cause great distress to them and their carers. Symptoms include agitation,
      aggression, wandering, shouting, depression, apathy and sleep disturbance. The
      safe and effective management of behavioral and psychiatric symptoms of
      Alzheimer's disease is one of the greatest challenges clinicians face.
      Traditionally, pharmacological interventions have been the mainstay of treatment
      but there is growing evidence for the effectiveness of a wide range of
      nonpharmacological measures. In this review, the evidence and appropriateness of
      both types of intervention for behavioral and psychiatric symptoms in Alzheimer's
      disease are discussed.

PMID- 15853509
TI  - Cholesterol homeostasis and the pathophysiology of Alzheimer's disease.
AB  - The past 4 years have seen a growing interest in cholesterol metabolism and its
      relationship to Alzheimer's disease. From the first report linking cholesterol
      and beta-amyloid metabolisms to the recent positive report on the use of
      atorvastatin (Lipitor, Pfizer Inc.), a cholesterol-lowering drug, in mild-to
      moderate Alzheimer's disease, this review examines the scientific progress
      pertaining to etiopathology of Alzheimer's disease over the past 15 years and the
      central role of lipids in this field of research. The role of key proteins
      involved in this metabolic pathway such as apolipoprotein E, lipoprotein lipase,
      caveolin, hydroxy-methylglutaryl Coenzyme A reductase, low-density lipoprotein
      receptors, cholesterol 24-hydroxylase, acyl-coenzyme A:cholesterol
      acyltransferase and beta-amyloid are discussed.

PMID- 15853510
TI  - Magnetic resonance and PET studies in the early diagnosis of Alzheimer's disease.
AB  - The demographics of aging identify an immediate need for the early diagnosis and
      development of dementia prevention strategies. Recent neuropathological studies
      have pointed to the early involvement of the hippocampus and entorhinal cortex in
      the progression of Alzheimer's disease in the brain. In particular, these studies
      have implicated tau-related pathology as an important cause of neuronal death. In
      addition, there is a large body of evidence showing that beta-amyloid, which has
      a predilection for the neocortex, is also involved early in the course of the
      disease and may also have toxic effects on cells. In vivo cerebrospinal fluid
      studies have shown that markers for these brain changes have a diagnostic value
      for Alzheimer's disease and that some measures also provide diagnostic
      specificity for Alzheimer's disease. Structural and metabolic imaging studies
      demonstrate brain changes in impaired and at-risk individuals. While currently
      available magnetic resonance and positron emission tomography techniques are not
      by themselves specific for the pathologic features of Alzheimer's disease, there
      are patterns of change that have been useful for the early diagnosis. As such,
      both prediction and longitudinal imaging studies demonstrate a capacity to
      recognize abnormalities that relate to future Alzheimer's disease and most
      recently to future mild cognitive impairment. This review highlights cross
      sectional, prediction, and longitudinal magnetic resonance and positron emission
      tomography imaging studies and attempts to put into perspective their utility for
      the early diagnosis of Alzheimer's disease, and for their utility to provide
      diagnostic specificity. It is concluded that there is considerable promise for an
      early and specific diagnosis for Alzheimer's disease by combining information
      from imaging and biomarker modalities.

PMID- 15853511
TI  - Role of progesterone and other neuroactive steroids in anxiety disorders.
AB  - It remains unexplained why a greater prevalence of anxiety disorders exists in
      women than in men, and how female hormone-related events (i.e., menstrual cycle
      and postpartum) can influence the course of anxiety disorders. It would appear
      logical that female hormones and their derivatives play a major role in these
      observations. The abundance of preclinical data demonstrating a role for sex
      hormones and their derivatives in anxiety-like behavior is in contrast to the
      relative paucity of experimental clinical data on the role of female hormones and
      neuroactive steroids in anxiety disorders. There is a dramatic potential for
      therapeutic anxiolytic activity of pharmacological compounds derived from
      powerful anxiolytic agents, such as the progesterone derivative,
      allopregnanolone. As a result, there is currently tremendous interest from the
      pharmaceutical industry in developing and testing such agents in anxiety
      disorders.

PMID- 15853512
TI  - Cognitive behavioral therapy in the treatment of schizophrenia.
AB  - This review outlines the role that cognitive behavioral therapy can play in
      specifically addressing the distress associated with the symptoms of
      schizophrenia, such as hallucinations and delusions. Some of the features that
      are given greater emphasis (or are a feature of working with people with
      psychotic illness), engagement, understanding the onset of the illness and work
      with hallucinations and delusional beliefs are outlined. The evidence base for
      the utility of cognitive behavioral therapy is considered, and the development
      and further application of cognitive behavioral therapy for schizophrenia and
      related disorders are outlined.

PMID- 15853513
TI  - Neuroglial responses to CNS injury: prospects for novel therapeutics.
AB  - Immune-mediated therapies can reduce the relapse rate in multiple sclerosis.
      However, there is no clear-cut evidence that any of these therapies substantially
      alter the long-term outcome for patients with progressive multiple sclerosis. The
      neurological disability that all too frequently accompanies multiple sclerosis is
      ultimately due to injury to target cells, principally oligodendroglia, within the
      nervous system. Recent data suggest that activation of leukemia inhibitory factor
      receptor signaling is an important component of a neurobiological response that
      serves to limit the extent of immune-mediated injury. Therefore, inactivation of
      this pathway could provide a novel approach to the treatment of demyelinating
      disease.

PMID- 15853514
TI  - Advances in the treatment of pediatric brain tumors.
AB  - Brain tumors are a heterogeneous group of neoplasms with different origins,
      pathobiologies, treatments and prognoses. The collective contributions from the
      fields of neuro-oncology, neurosurgery, radiation oncology, neurology,
      neuropathology, neuroradiology and molecular biology have all led to significant
      advances in the treatment of certain brain tumors. Ideas from these fields, under
      the cooperative umbrella of clinical cancer trial consortia, have been tested in
      large-scale studies. As a result, patient survivals have increased markedly for
      these tumor types. Unfortunately, there are certain brain tumors in childhood,
      such as the diffuse intrinsic pontine glioma and atypical teratoid rhabdoid
      tumor, for which survival advantages have not been found. This review will
      discuss the current and possible future therapies of the most common pediatric
      brain tumors and highlight some of the novel imaging modalities that are used pre
      and intraoperatively.

PMID- 15853515
TI  - Cluster headache: focus on emerging therapies.
AB  - Cluster headache is a strictly unilateral headache that occurs in association
      with cranial autonomic features. It is an excruciating syndrome and is probably
      one of the most painful conditions known to mankind with female patients
      describing each attack as being worse than childbirth. In most patients, it has a
      striking circannual and circadian periodicity. This disorder has a highly
      stereotyped clinical phenotype and responds to specific therapies, thereby
      underlying the importance of distinguishing it from other primary headache
      syndromes. In this review, the clinical manifestations, differential diagnosis,
      diagnostic workup and treatment options for this syndrome have been outlined.

PMID- 15853516
TI  - On the way to cure epilepsy.

PMID- 15853517
TI  - Reducing the burden of care in dementia through the amelioration of BPSD by drug
      therapy.

PMID- 15853519
TI  - Adderall XR: long acting stimulant for single daily dosing.
AB  - Adderall XR (SLI381) is the latest addition to the group of psychostimulant
      formulations, which provides the mixed amphetamine salts contained in Adderall as
      a single-daily dose formulation. Adderall XR is indicated for the treatment of
      attention deficit hyperactivity disorder in children and adolescents, with recent
      US Food and Drug Administration approval for attention deficit hyperactivity
      disorder in adults. Novel and important aspects of Adderall XR is its 12 h
      duration of action, relative superior efficacy to nonstimulant atomoxetine in a
      comparator trial, and significant quality of life impact in children, confirmed
      by the largest effectiveness trial yet to be performed for any attention deficit
      hyperactivity disorder therapy. Potentially important benefits of Adderall XR are
      proven safety and efficacy in adults with attention deficit hyperactivity
      disorder and positive postmarketing findings in treating oppositional defiant
      disorder -- the most common comorbidity in children with attention deficit
      hyperactivity disorder. This review summarizes the important properties of
      Adderall XR, to include a distinct two-stage delivery system and combination of
      active ingredients, offering unique advantages. Relevant clinical trials and the
      newest data from meeting reports are also discussed.

PMID- 15853520
TI  - Zonisamide: newer antiepileptic agent with multiple mechanisms of action.
AB  - Zonisamide (Zonegran, Eisai, Inc.) is a broad spectrum antiepileptic drug
      indicated for use as adjunctive therapy in the treatment of partial seizures.
      Zonisamide has multiple mechanisms of action, which may explain widespread
      reports of its utility in focal epilepsy and generalized epilepsy, and for
      nonseizure disorders such as headache and neuropathic pain. Zonisamide has been
      available in Japan since 1989 and became available in the USA in 2002. The rights
      to this drug in North America and Europe were recently acquired by Eisai Co. A
      review of the chemical properties, pharmacokinetics, metabolism, potential
      mechanisms of action, efficacy in seizure and nonseizure disorders, and
      tolerability was therefore thought to be timely.

PMID- 15853521
TI  - Primary prevention of epilepsy in patients with different epileptogenic
      conditions.
AB  - Epileptic seizures are a common complication of several clinical conditions
      affecting the CNS. In these cases, the occurrence of seizures and epilepsy may
      increase the functional damage provoked by the underlying epileptogenic condition
      and affect the patient's quality of life to a significant extent. Therefore, the
      search of effective means for primary prevention of seizures and epilepsy is
      necessary in these cases. However, the use of antiepileptic drugs for the primary
      prevention of seizures and epilepsy can be considered only if the ratio between
      efficacy, safety and tolerability of treatment is favorable, in that the
      advantages, in terms of seizure prevention, outweigh the disadvantages in terms
      of adverse effects and overall costs of treatment. In this article, the efficacy,
      safety and tolerability of antiepileptic drugs for the primary prevention of
      seizures and epilepsy are reviewed. The areas covered include: the definition of
      early (provoked) and late (unprovoked) seizures; knowledge of the overall risk of
      seizures and epilepsy in CNS disorders for which primary prevention of seizures
      can be attempted; rationale for the use of antiepileptic drugs for the primary
      prevention of epilepsy; experimental data on the antiepileptogenic properties of
      antiepileptic drugs; available literature findings on the prevention of early and
      late seizures, with specific emphasis on randomized clinical trials; and the main
      problems with experimental trials for the primary prevention of epileptic
      seizures. On this basis, practice recommendations for the primary prevention of
      epilepsy will be offered where indicated. Suggestions for future research are
      also made as concluding remarks, by indicating the areas of investigation and the
      design of future studies.

PMID- 15853522
TI  - Use of psychotropic drugs in patients with epilepsy: interactions and seizure
      risk.
AB  - It is now accepted that patients with epilepsy are more prone than the general
      population to develop psychiatric disorders, being significantly at risk due to
      psychosocial reasons, the presence of electrophysiologic and anatomopathologic
      abnormalities mainly in the limbic system, and because they are taking
      antiepileptic drugs which may have negative psychotropic effects. It is also
      known that many patients with epilepsy sometimes receive psychotropic medications
      on account of their psychiatric symptoms. This review focuses on the main
      problems that a clinician may encompass when treating psychiatric disorders in
      patients with epilepsy. On one hand, the effects of antiepileptic drugs on mood
      and behavior for a correct differential diagnosis of psychiatric symptoms. On the
      other hand, the main factors that may affect choice of therapy, patients'
      response and compliance, when prescribing antidepressants or antipsychotic drugs,
      drug interactions and the potential proconvulsive risk are reviewed.

PMID- 15853523
TI  - Brain stimulation in the treatment of epilepsy.
AB  - Stimulation of the brain for the treatment of epilepsy, indirectly via the vagus
      nerve and directly through intracranial targets, is feasible and has increased in
      use and complexity over the past 10 years. Vagus nerve stimulation is widely
      applied and the present indications and outcomes together with possible ways in
      which the treatment could be refined are reviewed. The application of stimulation
      to deep-brain targets is also reviewed along with present practice and results.
      Possible developments in the use of direct intracranial stimulation are also
      considered.

PMID- 15853524
TI  - Recent advances in the neuropathology of focal lesions in epilepsy.
AB  - This review addresses the main neuropathologic advances that have been made over
      recent years in the study of focal lesions in patients with epilepsy undergoing
      surgical treatment. There have been revisions and simplifications to the
      classification of focal cortical dysplasias. Hippocampal sclerosis is a well
      characterized lesion but further pathologic studies have explored its possible
      relationship to temporal lobe developmental lesions, ongoing neurogenesis and
      mechanisms of its epileptogenicity. The important contribution of astrocytes to
      epileptogenesis is also unfolding and is briefly discussed, as are the possible
      cellular mechanisms of drug resistance.

PMID- 15853525
TI  - Outcome measures for clinical trials in Parkinson's disease: achievements and
      shortcomings.
AB  - Three areas of intense investigation in Parkinson's disease clinical trials
      include symptomatic treatment of Parkinsonism, disease-modifying therapy (or
      neuroprotection), and the prevention and treatment of motor complications of
      dopaminergic therapy. Difficulty interpreting the results of many studies in
      recent years has been attributed to problems with the chosen outcome measures.
      This article reviews the most common outcome measures used, assesses their
      positive attributes and proposes needs for future research. The Unified
      Parkinson's disease Rating Scale has been extensively validated and is by far the
      most common outcome measure used in trials of symptomatic therapy. Ambiguities in
      the response scale descriptors, poor inter-rater reliability of some items and a
      lack of items addressing nonmotor features of the disease are being addressed in
      a revision of the scale. Quality of life outcomes are being used in the minority
      of clinical trials, and no single generic or disease-specific quality of life
      measure is being used most frequently. Additional work validating several of the
      disease-specific instruments is needed. When a generic measure is used, its
      validity for use in Parkinson's disease must be critically assessed despite its
      previously established validity in other diseases. With respect to measuring
      motor complications, significant unmet needs include a consensus as to the best
      way to define the first motor complication and validating time to the first
      occurrence of motor complications as a surrogate of future disability and quality
      of life. Measuring the effectiveness of a potential neuroprotective agent
      presents unique challenges, particularly since symptomatic effects of the
      experimental agent or concomitant treatment can obscure any neuroprotective
      effects. Study designs and biomarkers are being developed that may overcome this
      problem. Currently, neuroimaging techniques that reflect function of the
      dopaminergic system are the most promising biomarkers but still require
      additional validation.

PMID- 15853526
TI  - Therapeutic potential of oxidant mechanisms in Alzheimer's disease.
AB  - Oxidative stress is a major feature and one of the earliest changes in
      Alzheimer's disease. The complex nature and genesis of oxidative damage in
      Alzheimer's disease can be partly answered by mitochondrial and redox-active
      metal abnormalities. Evidence indicates that in the initial phase of Alzheimer's
      disease development, amyloid-beta deposition and hyperphosphorylated tau,
      hallmarks of the disease, are consequences of oxidative stress. Therefore, the
      authors propose that oxidative modifications in early stages of Alzheimer's
      disease may actually serve as a homeostatic response or compensatory mechanism
      against stressful agents resulting in a shift of neuronal priority from normal
      function to basic survival. Since the cause of Alzheimer's disease
      pathophysiology remains controversial, several and distinct therapeutic
      strategies have been tried to avoid, or at least reduce, the development of this
      neurodegenerative disorder. In this line, the inherent theoretical limitations of
      secretase inhibitors and immunotherapy, aimed to avoid the production or clear
      amyloid-beta from the brain is discussed. Promising antioxidant strategies, with
      the focus on fighting oxidative stress, are highlighted. Currently, antioxidant
      strategies appear to be the most encouraging therapeutics in reducing the
      clinical manifestation and evolution of Alzheimer's disease.

PMID- 15853527
TI  - Treatment of low-grade gliomas in children: an update.
AB  - Pediatric low-grade gliomas are a heterogeneous group of tumors that require
      integration of the pathology and radiographic appearance with the biologic
      heterogeneity associated with these tumors. Balancing surgery, radiation and
      chemotherapy to optimize disease control while limiting treatment-related
      morbidity is of critical importance in this susceptible population and is the
      focus of this review.

PMID- 15853528
TI  - Treating brain metastases: current approaches and future directions.
AB  - Brain metastases frequently present with neurologic signs or symptoms in a
      patient with a history of cancer. The finding of a brain metastasis is usually
      associated with terminal disease. However, patients with brain metastases are a
      heterogeneous group. Therefore, the treatment of brain metastases must be
      tailored to each individual patient. In this article, which patients with brain
      metastases benefit from surgical resection, radiosurgery and whole-brain
      radiation therapy are reviewed. Reports of treating patients with brain
      metastases with chemotherapy are also reviewed and data that supports
      prophylactic treatment of the brain for select patients is discussed. This review
      aims to provide a framework for treating patients with different presentations of
      brain metastases and to highlight important avenues for future research.

PMID- 15853529
TI  - Primary and secondary prevention of stroke by antihypertensive drug treatment.
AB  - Hypertension is the most powerful risk factor for stroke. Antihypertensive drug
      treatment reduces the incidence of stroke. In a meta-analysis of actively
      controlled trials, calcium-channel blockers, including (-8%; p = 0.07) or
      excluding verapamil (-10%; p = 0.02), as well as angiotensin Type 1 receptor
      blockers (-24%; p = 0.0002) resulted in better stroke prevention than the old
      drugs (diuretics or beta-blockers), whereas the opposite trend was observed for
      angiotensin-converting enzyme inhibitors (+10%; p = 0.03). An overview of six
      trials conducted in patients with a history of cerebrovascular disease
      demonstrated that blood pressure-lowering therapy reduced stroke recurrence by
      25% (p = 0.004). A meta-regression analysis showed that within-trial differences
      in systolic blood pressure accounted for the prevention of stroke in most trials.
      This finding was corroborated by the recently published Valsartan
      Antihypertensive Long-term Use Evaluation trial.

PMID- 15853530
TI  - Learning from headaches? Old problems and new insights in migraine.

PMID- 15853532
TI  - Oral almotriptan: practical uses in the acute treatment of migraine.
AB  - Almotriptan (Almogran, Lundbeck; Almirall Prodesfarma; Axert, Ortho-McNeil) is a
      novel 5-HT(1B/1D) receptor agonist (triptan) that is widely available on
      prescription for the acute treatment of migraine. Almotriptan has pharmacodynamic
      and pharmacokinetic profiles that make it suitable for use in this indication. It
      is a potent agonist at 5-HT(1B), (1D) and (1F) receptors, while having a low
      affinity for other 5-HT receptors. It is also a potent inhibitor of neurogenic
      inflammation. Almotriptan has a high oral bioavailability, is absorbed rapidly,
      has a relatively short plasma half-life and its route of elimination presents few
      potential problems. Placebo-controlled dose-finding studies have demonstrated
      that almotriptan tablets are effective and well-tolerated in the acute treatment
      of migraine, with a 12.5 mg dose providing the best balance between efficacy and
      tolerability. Large placebo-controlled studies show that the efficacy of oral
      almotriptan is comparable with that of the other oral triptans. In direct
      comparator-controlled studies, almotriptan was as effective as sumatriptan 50 and
      100 mg but had a superior tolerability profile. Furthermore, the efficacy and
      tolerability of almotriptan is sustained in the long term following open-label
      administration. Meta-analyses and post hoc analyses of clinical data confirm
      these findings. In conclusion, almotriptan 12.5 mg is a good therapeutic choice
      for the symptomatic treatment of acute migraine attacks.

PMID- 15853533
TI  - Divalproex sodium in the treatment of adults with bipolar disorder.
AB  - Divalproex sodium (Depakote, Abbott Laboratories) is an anticonvulsant with well
      established efficacy in the treatment of bipolar I disorder, manic or mixed
      episode. Over the past 10 years, an increased number of studies indicate that
      divalproex has a broad spectrum of activity in the treatment of bipolar
      depression and rapid cycling, psychotic symptoms, impulsive aggression and post
      traumatic stress disorder. Newer formulations of divalproex, namely the extended
      release formulation, are now available. The improved tolerability and convenience
      of the once-daily extended-release formulation has a significant potential to
      improve patient compliance and thus, clinical and functional outcomes. The use of
      divalproex in the treatment of bipolar and other related psychiatric disorders is
      reviewed.

PMID- 15853534
TI  - Lamotrigine for bipolar disorder: translating research into clinical practice.
AB  - Lamotrigine (Lamictal, GlaxoSmithKline) is a recently developed anticonvulsant
      which has been investigated for efficacy in bipolar disorder. Increasing evidence
      indicates that it may have a different therapeutic profile than more established
      first-line mood stabilizers such as lithium and valproate. In particular,
      evidence from well-designed trials suggests efficacy for acute management and
      prophylaxis of bipolar depression but not mania. However, clinically relevant
      drug interactions and side effects can occur with lamotrigine, including benign
      to serious rash. The objectives of this drug profile are to review the basic
      chemical and pharmacological characteristics of lamotrigine, critically examine
      the growing body of research literature on its clinical use in the treatment of
      bipolar disorder, and review the safety and tolerability of lamotrigine as well
      as drug interactions relevant to clinical practice. Practical recommendations
      regarding titration and the management of rash are offered.

PMID- 15853535
TI  - Venlafaxine in the treatment of anxiety disorders.
AB  - Venlafaxine extended-release (Effexor XR, Wyeth-Ayerst Co.) is a novel, dual
      acting serotonin-norepinephrine reuptake inhibitor antidepressant, which inhibits
      the synaptic reuptake of both serotonin and norepinephrine. Controlled trials
      have demonstrated the efficacy and safety of venlafaxine in the treatment of
      anxiety disorders including social anxiety disorder, generalized anxiety
      disorder, post-traumatic stress disorder, panic disorder and obsessive-compulsive
      disorder. Generally well-tolerated with side effects that usually abate with
      continued treatment, venlafaxine is an important alternative to the selective
      serotonin reuptake inhibitors for patients with anxiety disorders.

PMID- 15853536
TI  - Diagnosis and pathophysiology of migraine.
AB  - Over the past 10 years there has been an explosion of knowledge about headache,
      particularly migraine. Fueled by new, highly effective therapeutic agents, vast
      resources have been invested in improving diagnostic accuracy and attempting to
      understand the mechanisms by which this symptom is generated. Public awareness
      has increased as has that of the medical community. Tools are now available to
      help diagnose particular types of headache and measure/monitor disability.
      Numerous pathophysiologic changes have been studied which may in turn increase
      the therapeutic armamentarium. With approximately 10% of the public suffering
      from migraine and with most of these cases remaining undiagnosed, it is likely
      that this segment of the healthcare market will continue to expand in the future.

PMID- 15853537
TI  - Future pharmacologic targets for acute and preventive treatments of migraine.
AB  - Advances in investigative research (e.g., functional magnetic resonance imaging)
      have made it possible to study putative migraine processes and better understand
      the pathophysiology of the disorder. Consequently, the apparent opposing vascular
      and neuronal theories of migraine are now reconciled into a neurovascular
      hypothesis that pieces together migrainous events and allows us to better target
      such events in the hope of providing safe and effective therapies. Parallel
      discoveries in the fields of pharmacology, physiology, genetics and other
      biomedical disciplines will lead to the development of optimal migraine
      therapeutics. Such discoveries have already yielded some major enhancement in
      acute migraine treatment with the development of sumatriptan (Imitrex,
      GlaxoSmithKline) and other triptans and the trajectory is likely to be
      exponential. Novel targets, such as calcitonin gene-related peptide antagonists
      and inhibitors of excitatory glutamatergic receptors, are leading the pack but
      many other promising targets are in development. The post-sumatriptan decades
      will witness treatment strategies that will improve the therapeutic index of
      acute therapies and others which will effectively and safely prevent migraine
      attacks.

PMID- 15853538
TI  - Behavioral treatment of migraine: current status and future directions.
AB  - The empirical support for three behavioral treatments (relaxation, biofeedback
      and cognitive therapy) for managing migraine headaches in children and adults is
      reviewed. Meta-analyses and evidence-based reports show that these approaches are
      of considerable value, they appear to work equally well when applied
      individually, in groups or in limited contact formats. Meta-analyses comparing
      behavioral and prophylactic medication show equivalent results. However, outcomes
      are optimized when these treatments are combined. Researchers are currently
      seeking to identify factors predictive of response to behavioral approaches.
      Patients experiencing medication-overuse, refractory, cluster or post-traumatic
      forms of headache or comorbid conditions present special challenges that can
      require intensive, comprehensive and multidisciplinary approaches to treatment.
      Behavioral treatments have met with mixed success for menstrual migraine in the
      few studies that have been conducted. This review concludes by highlighting
      directions for future research efforts such as importing treatments to settings
      where headache patients most often seek care and developing algorithms for
      optimizing combinations of behavioral and pharmacological treatments to enhance
      effectiveness, reduce costs, minimize dosing requirements and improve adherence
      to needed medications. Other research efforts include developing treatments that
      target the underlying pathophysiology more directly, gaining a greater
      understanding of mediators and moderators of behavioral treatments, exploiting e
      technology for assessment and treatment, and assessing outcome in multiple ways-
      such as quality of life.

PMID- 15853539
TI  - Etiology of primary headaches: the importance of genes and environment.
AB  - Results from twin studies show that genes play an important role for
      susceptibility to migraine. The propensity for migraine to run in some families
      but not in others arises predominantly from alleles shared by family members and
      not the shared family environment, and that environmental influences on migraine
      are unique to the affected family member. The main genetic and environmental
      architecture for the other two major primary headaches, tension-type and cluster,
      remains to be elucidated. This review focuses on recent advances in twin studies
      of primary headaches and the future prospects are outlined.

PMID- 15853540
TI  - Evaluation and management of headache in primary care.
AB  - Headache disorders are ubiquitous, common, disabling and to a very large extent
      treatable in primary care. In this review, the important headache disorders are
      described together with their impact on public health. Suggestions are set out
      for their optimal management, although many of these are necessarily based more
      on expert opinion than on formal evidence, since clinical trials have covered
      only narrow areas of headache treatment. Most people whose lives are adversely
      affected by headache disorders benefit from drug interventions, either acute or
      preventative, but other forms of treatment are always important and should never
      be overlooked. An important disorder is entirely iatrogenic: its recognition is
      crucial to its effective management, which requires medication withdrawal. Future
      research is needed not only into the mechanisms of headache causation, as a
      prerequisite for the development of better treatments, but also into public
      health aspects seeking an explanation of (and remedy for) the low priority given
      worldwide to headache-related healthcare despite the severe human and
      socioeconomic consequences.

PMID- 15853541
TI  - Chemokine network in multiple sclerosis: role in pathogenesis and targeting for
      future treatments.
AB  - Multiple sclerosis is the most common inflammatory disorder of the CNS. Evidence
      suggests that an immunomediated mechanism plays a crucial role during the
      development of the disease. Currently, two classes of immunomodulatory agents --
      interferon-beta and glatiramer acetate (Copaxone, Teva Pharmaceutical
      Industries), have been approved for the long-term treatment of multiple
      sclerosis. New drugs which effectively target the immunological processes
      occurring in multiple sclerosis have been proposed. This review summarizes the
      immunological background that occurs during the pathogenesis of multiple
      sclerosis focusing on chemokines and related receptors. The effects of standard
      treatments on the immune system are analyzed along with the current knowledge of
      potential new immunomodulatory molecules, such as antiadhesion molecules,
      statins, estriol, cannabinoids, neurotrophic factors and chemokine antagonists.

PMID- 15853542
TI  - Disease-modifying drugs for the early treatment of multiple sclerosis.
AB  - The introduction of new immunomodulatory therapies such as, interferon-beta,
      glatiramer acetate (Copaxone, Teva Pharmaceutical Industries) and mitoxantrone
      (Ralenova, Wyeth Pharma; Novantrone, Immunex Corp.) has considerably improved the
      therapeutic options for patients with multiple sclerosis. These agents have been
      shown to reduce relapse rate, slow down progression of disability and prevent the
      accumulation of magnetic resonance imaging lesion load in clinically definite
      multiple sclerosis. Moreover, two formulations of interferon-beta delayed
      conversion into clinically definite multiple sclerosis in patients with
      clinically isolated syndromes suggestive of multiple sclerosis. Since axonal
      damage leading to irreversible neurological disability is already present early
      at the onset of the disease, immunomodulatory therapy should start as soon as
      possible. This article reviews the arguments for the early initiation of therapy
      and provides an overview of clinical studies dealing with the early treatment of
      multiple sclerosis.

PMID- 15853543
TI  - Deep brain stimulation in the treatment of neurological and psychiatric disease.
AB  - Deep brain stimulation has become a topic of intense interest both from a
      clinical and basic science perspective. Its indications, currently including
      Parkinson's disease, tremor and dystonia, may expand in the future to include not
      only other movement disorders but also epilepsy, obsessive-compulsive disorder
      and other neuropsychiatric conditions. The mechanism(s) of action of deep brain
      stimulation have only recently begun to be characterized and have already yielded
      surprises that may open the door to a greater expansion of the indications for
      this novel and powerful therapeutic intervention.

PMID- 15853544
TI  - Do minimally invasive procedures have a place in the treatment of chronic low
      back pain?
AB  - Chronic low back pain is the leading cause of disability in the industrialized
      world. Medical and surgical treatments remain costly despite limited efficacy.
      The field of 'interventional pain' has grown enormously and evidence-based
      practice guidelines are systematically developed. In this article, the vast,
      complex and contradictory literature regarding the treatment of chronic low back
      pain is reviewed. Interventional pain literature suggests that there is moderate
      evidence (small randomized, nonrandomized, single group or matched-case
      controlled studies) for medial branch neurotomy and limited evidence
      (nonexperimental one or more center studies) for intradiscal treatments in
      mechanical low back pain. There is moderate evidence for the use of
      transforaminal epidural steroid injections, lumbar percutaneous adhesiolysis and
      spinal endoscopy for painful lumbar radiculopathy, and spinal cord stimulation
      and intrathecal pumps mostly after spinal surgery. In reality, there is no gold
      standard for the treatment of chronic low back pain, but these results appear
      promising.

PMID- 15853545
TI  - Pain management in neonates.
AB  - Multiple lines of evidence suggest an increased sensitivity to pain in neonates.
      Repeated and prolonged pain exposure may affect the subsequent development of
      pain systems, as well as potentially contribute to alterations in long-term
      development and behavior. Despite impressive gains in the knowledge of neonatal
      pain mechanisms and strategies to treat neonatal pain acquired during the last 15
      years, a large gap still exists between routine clinical practice and research
      results. Accurate assessment of pain is crucial for effective pain management in
      neonates. Neonatal pain management should rely on current scientific evidence
      more than the attitudes and beliefs of care-givers. Parents should be informed of
      pain relief strategies and their participation in the health care plan to
      alleviate pain should be encouraged. The need for systemic analgesia for both
      moderate and severe pain, in conjunction with behavioral/environmental approaches
      to pain management, is emphasized. A main sources of pain in the neonate is
      procedural pain which should always be prevented and treated. Nonpharmacological
      approaches constitute important treatment options for managing procedural pain.
      Nonpharmacological interventions (environmental and preventive measures, non
      nutritive sucking, sweet solutions, skin-skin contact, and breastfeeding
      analgesia) can reduce neonatal pain indirectly by reducing the total amount of
      noxious stimuli to which infants are exposed, and directly, by blocking
      nociceptive transduction or transmission or by activation of descending
      inhibitory pathways or by activating attention and arousal systems that modulate
      pain. Opioids are the mainstay of pharmacological pain treatment but there are
      other useful medications and techniques that may be used for pain relief.
      National guidelines are necessary to improve neonatal pain management at the
      institutional level, individual neonatal intensive care units need to develop
      specific practice guidelines regarding pain treatment to ensure that all staff
      are familiar with the effects of the drugs being used and to guarantee access and
      safe administration of pain treatment to all neonates.

PMID- 15853546
TI  - C-reactive protein, cardiovascular disease and stroke: new roles for an old
      biomarker.
AB  - Stroke is a leading cause of death and disability worldwide. A new and exciting
      development in cardiovascular disease is the recognition of the role of
      inflammation in atherosclerosis. C-reactive protein, an acute phase reactant,
      appears to be a promising biomarker for cardiovascular disease, possibly more
      predictive than cholesterol and also may play an etiological role. C-reactive
      protein also appears to be predictive of stroke risk, although less so in the
      elderly. Although the number of studies on stroke (apart from cardiovascular
      disease) is limited, there is a significant graded increase in stroke risk within
      the low-to-high normal range of C-reactive protein. C-reactive protein is readily
      amenable to treatment with anti-inflammatory drugs, such as aspirin and statins.
      New and increasingly available high-sensitivity assays may make C-reactive
      protein a standard screening tool for cardiovascular disease.

PMID- 15853547
TI  - Molecular biology of channelopathies: impact on diagnosis and treatment.
AB  - Channelopathies are genetically determined ion channel alterations that lead to
      acute and transient symptoms in subjects who otherwise appear to be normal. This
      article reviews the recent progression of biomolecular studies that have
      clarified the mechanisms by which gene mutations may result in alterations of
      excitable tissues responsible for episodic neurological, neuromuscular and
      cardiac disorders, defined as channelopathies. The development of technologies
      capable of testing pharmacological agents in vitro on mutated channels expressed
      in cell lines makes it possible to define a more rational use of the available
      drugs acting on ion channels, and to design new molecules specifically targeted
      to known channel dysfunctions and new ones that could be identified by future
      genetic studies.

PMID- 15853548
TI  - Oxidative injury in epilepsy: potential for antioxidant therapy?
AB  - Biological ill effects of oxidative injury from excess free radical production
      are implicated in many human conditions. Epilepsy is a chronic, dynamic
      neurological disorder associated with ongoing neuronal damage, particularly when
      uncontrolled. Oxidative injury may play a role in the initiation and progression
      of epilepsy, and therapies aimed at reducing oxidative stress may ameliorate
      tissue damage and favorably alter the clinical course. There is abundant in vivo
      evidence of oxidative injury in animal models of epilepsy and for efficacy of
      antioxidant therapy in reducing this injury in animal models of epileptogenesis.
      However, there is sparse direct clinical data on the use of antioxidants in human
      epilepsy. This review examines the evidence for the role of oxidative injury in
      epilepsy, the rationale for use of antioxidant therapy in epilepsy and appraises
      the current clinical performance of the studies of antioxidant therapies.

PMID- 15853550
TI  - Treatment of neoplastic meningitis: what is the standard of care?
AB  - This discussion will focus on defining the standard of care for neoplastic
      meningitis, including: What is the role of radiation therapy? What are first-line
      pharmacotherapeutic agents? Is combination therapy useful? What is the role of
      corticosteroids?

PMID- 15853551
TI  - Primary CNS lymphoma: is there a role for prophylaxis against lymphomatous
      meningitis?
AB  - This part of the program extends the previous discussion of metastatic CNS
      disease to prophylaxis of primary CNS lymphoma against meningeal involvement.

PMID- 15853552
TI  - Leukemia and lymphoma: what is the role for intrathecal prophylactic treatment in
      adults?
AB  - The final subject to be addressed is the role of prophylactic treatment for
      hematologic tumors. Prophylactic intrathecal therapy is the standard of care in
      pediatric acute lymphocytic leukemia patients. Should prophylaxis be applied to
      adult patients with leukemia? In addition and as an extension of the adult
      leukemia patient discussion, is there a role for intrathecal prophylaxis in
      patients with lymphoma, a population at risk for neoplastic meningitis?

PMID- 15853553
TI  - Defining patients at risk for neoplastic meningitis: what parameters can be used
      to determine who should be treated?
AB  - While a growing body of clinical research is defining how better to treat
      neoplastic meningitis, questions regarding which parameters can be used to define
      who to treat remain. This discussion initiates the clinical core and practical
      components of the symposium.

PMID- 15853554
TI  - Antithrombotic therapy for prevention of recurrent stroke in the new millennium.

PMID- 15853556
TI  - Galantamine: use in Alzheimer's disease and related disorders.
AB  - Galantamine (Reminyl) has long been used as a traditional medicine and has an
      interesting pharmacology as it is both a reversible acetylcholinesterase
      inhibitor and an allosteric potentiator of nicotinic cholinergic receptors. The
      efficacy of galantamine has been studied in an extensive development program in
      Alzheimer's disease, and mixed and vascular dementia. Randomized, double-blind,
      placebo-controlled trials of up to 6 months duration and subsequent open-label
      follow-up studies have produced a broad spectrum of beneficial effects on
      cognitive and noncognitive disease symptoms. Apparent benefits for caregivers
      paralleled these, with a potentially reduced burden and cost. It appears that
      early and continued treatment maximizes the observed effects, which translate
      into economic terms, when applied to cost-effectiveness models. Overall,
      galantamine has a broad ranging efficacy and tolerability across an increasing
      range of conditions.

PMID- 15853557
TI  - Parecoxib: a shift in pain management?
AB  - Parecoxib (Dynastat) is a parenteral cyclooxygenase-2 inhibitor available in
      Europe. Clinical trials have reported a benefit in reducing pain following oral,
      orthopedic, gynecologic and cardiac surgeries. The overall efficacy was dose
      related and similar to ketorolac (Toradol). Several trials reported an opioid
      sparing effect with parecoxib. No trials have reported significantly fewer opioid
      related gastrointestinal side effects (e.g., nausea, vomiting, constipation and
      intestinal ileus) when opioids were administered with parecoxib versus placebo.
      Gastroduodenal ulcers, gastric ulcers and duodenal ulcers or erosions were less
      common with parecoxib than ketorolac. Parecoxib does not affect platelet
      aggregation, interfere with the antiplatelet affect of aspirin, affect
      prothrombin and partial thromboplastin time or platelet counts when administered
      with heparin.

PMID- 15853558
TI  - Ziprasidone: a novel psychotropic with unique properties.
AB  - Ziprasidone (Geodon) is a relatively new atypical antipsychotic medication with a
      unique pharmacological profile. It is indicated for the treatment of
      schizophrenia, but has also often been used off-label for other uses. This review
      summarizes its important properties, specifically the pharmacodynamic parameters,
      receptor-binding profile and relevance to clinical outcomes, side effects, and
      potential for drug-drug interactions and established clinical indications. Novel
      therapeutic applications and relevant clinical trials or reports are also
      examined. The authors review the current market and speculate on likely changes
      in 5 years.

PMID- 15853559
TI  - Is clozapine antisuicidal?
AB  - Suicide accounts for approximately 10% of patient deaths in schizophrenia. The
      atypical antipsychotic clozapine (Clozaril), successful in treatment-resistant
      patients with schizophrenia, may have an additional antisuicidal effect. Numerous
      published reports, including the collaborative International Suicide Prevention
      Trial, have compared mortality rates between clozapine recipients and patients
      receiving other forms of antipsychotic treatment and observed a significant
      reduction in patient risk for suicide with clozapine therapy. Preliminary reports
      indicate improvements in suicidality in schizophrenia patients treated with other
      modern atypical antipsychotics, for example olanzapine [Zyprexa], risperidone
      [Risperdal] and sertindole [Serdolect], but further investigation is required to
      clarify their role as antisuicidal drugs. It has been estimated that 53 suicides
      in treatment-resistant patients could have been prevented by clozapine, but the
      number of lives saved may be significantly higher if clozapine therapy was
      extended to treatment responders at a high risk for suicide.

PMID- 15853560
TI  - Paroxetine in panic disorder: clinical management and long-term follow-up.
AB  - Panic disorder is one of the most common anxiety disorders and has a lifetime
      prevalence of 3-5%. Panic attacks can begin at any age, but commonly have their
      onset in early adulthood between the ages of 20 and 40 years. Naturalistic data
      has shown that panic disorder has a chronic and relapsing course. Panic disorder
      is reported to be associated with an increased risk of suicidal behavior and
      comorbid psychiatric diagnoses such as depression and substance abuse. Currently,
      recommended treatment modalities for panic disorder include the use of
      antidepressant pharmacotherapy and/or cognitive behavioral therapy. Paroxetine is
      unique among the selective serotonin reuptake inhibitors since, in addition to
      its effect on the CNS serotonergic neurotransmission, it also has mild
      noradrenergic properties demonstrated to be effective in the treatment of anxiety
      disorders and depression. Paroxetine treatment has the potential to cause weight
      gain and sexual dysfunction, primarily anorgasmia and ejaculatory dysfunction for
      the long term. In the short-term, treatment causes nausea, gastrointestinal
      disturbances, irritability, headaches and eating and sleeping difficulties.
      Paroxetine is an example of an selective serotonin reuptake inhibitor agent,
      which has been well studied in the treatment of panic disorder and is efficacious
      and well-tolerated. Paroxetine pharmacotherapy has been recommended to be
      continued for 1 year as specified in the treatment guidelines set by the American
      Psychiatric Association in the treatment of panic disorder.

PMID- 15853561
TI  - Sumatriptan: a decade of use and experience in the treatment of migraine.
AB  - The migraine-specific triptans have revolutionized the treatment of migraine and
      are usually the drugs of choice to treat a migraine attack in progress.
      Sumatriptan (Imitrex) has been available for the longest time within the class,
      is most flexible in form and has been given successfully to the most number of
      patients. It is useful for the full range of attacks experienced by a migraine
      suffer. The aim of this review is to provide an overview of the first 10 years of
      the use of sumatriptan.

PMID- 15853562
TI  - Drug treatment of poststroke aphasia.
AB  - Impairment of language function (aphasia) is one of the most common neurological
      symptoms after stroke. Approximately one in every three patients who have an
      acute stroke will suffer from aphasia. The estimated incidence and prevalence of
      stroke in Western Europe is 140 and 800 per 100,000 of the population. Aphasia
      often results in significant disability and handicap. It is a major obstacle for
      patients to live independently in the community. When recovery from aphasia
      occurs, it is usually incomplete and patients are rarely able to return to full
      employment and other social activities. Currently, the main treatment for aphasia
      is conventional speech and language therapy. However, the effectiveness of this
      intervention has not been conclusively demonstrated and empirical observations
      suggest that spontaneous biological recovery may explain most of the improvement
      in language function that occurs in aphasics. The generally poor prognosis of the
      severe forms of poststroke language impairment (Broca, Wernicke and global
      aphasia), coupled with the limited effectiveness of conventional speech and
      language therapy has stimulated the search for other treatments that may be used
      in conjunction with speech and language therapy, including the use of various
      drugs. Dopamine agonists, piracetam (Nootropil), amphetamines, and more recently
      donepezil (Aricept), have been used in the treatment of aphasia in both the acute
      and chronic phase. The justification for the use of drugs in the treatment of
      aphasia is based on two types of evidence. Some drugs, such as dextroamphetamine
      (Dexedrine), improve attention span and enhance learning and memory. Learning is
      an essential mechanism for the acquisition of new motor and cognitive skills, and
      hence, for recovery from aphasia. Second, laboratory and clinical data suggest
      that drug treatment may partially restore the metabolic function in the ischemic
      zone that surrounds the brain lesion and also has a neuroprotective effect
      following acute brain damage. An example of this is the nootropic agent
      piracetam. Extensive animal studies have demonstrated the beneficial effects of
      this and other drugs on neural plasticity, but data on humans are still sparse.
      This review provides a critical analysis of the current evidence of the
      effectiveness of these drugs in the treatment of acute and chronic aphasia.

PMID- 15853563
TI  - Road to recovery: drugs used in stroke rehabilitation.
AB  - The practice of neurorehabilitation is unique in that it supplements treatments
      with medications which complement and expedite the rehabilitation process. In
      stroke rehabilitation, medications can be used not only to treat poststroke
      secondary complications but also to facilitate recovery. Since only thrombolytics
      have been demonstrated to be effective in minimizing brain damage and maximizing
      functional outcome, intensive rehabilitation remains the most significant and
      important means by which stroke survivors possibly may maximize stroke recovery.
      There is an opportunity to complement intensive rehabilitation with pharmacologic
      interventions that facilitate the recovery of damaged neurons as well as plastic
      responses in underutilized and unused brain tissue. However, few of these
      medications have been approved for these indications or have been subjected to
      large randomized clinical trials. Nonetheless, this review identifies areas in
      stroke rehabilitation that can be addressed with neuropharmacologic agents, lists
      specific medications currently used to treat these conditions and describes the
      evidence that supports the recommendations for these medications.

PMID- 15853564
TI  - Stroke prevention with lipid-lowering therapy.
AB  - Despite great progress in the medical sciences, the effects of stroke in the
      modern world are profound, both in the aspect of death and disability it causes,
      as well as the economic demands it poses. The most important modifiable risk
      factors of stroke are arterial hypertension, heart disease, cigarette smoking and
      transient ischemic attacks. Secondary risk factors include hyperlipidemia,
      obesity and physical inactivity. The role of lipids in atherosclerosis and
      cerebral vascular events, and the influence of lipid-lowering therapies on stroke
      occurrence is a subject of debate in the medical literature. The aim of this
      review is to answer the basic question of whether lipid-lowering therapy should
      be used routinely in stroke prevention.

PMID- 15853565
TI  - HMG CoA reductase inhibitors (statins): use in stroke prevention and outcome
      after stroke.
AB  - The use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins)
      has been demonstrated to reduce the risk of primary and secondary ischemic stroke
      in patients with ischemic heart disease (relative risk reduction is 20-30%),
      confirmed by several prospective randomized placebo-controlled trials. At least
      one large prospective trial has also shown a similar benefit in patients without
      underlying ischemic heart disease. This is in contrast to an open-labeled trial
      conducted in the USA, which failed to demonstrate a significant benefit of
      statins in reducing stroke risk in hypertensive hyperlipidemic patients. It is
      less clear if treatment with statins before or after the onset of ischemic stroke
      also reduces its severity (improves outcome). Experimental animal studies where
      mice were pretreated with statins, demonstrated a reduced infarct size compared
      with untreated animals. Treatment with statins after stroke onset has also been
      demonstrated to enhance recovery without influencing infarct size (by increased
      angiogenesis, synaptogenesis and blood flow). A few clinical retrospective
      studies have demonstrated similar results. Prospective blinded placebo-controlled
      trials to test these findings are still lacking. This review discusses the
      various prospective trials in stroke prevention and available data on the effects
      of statins in improving outcome of established ischemic stroke. Alternate
      mechanisms of statins besides their lipid-lowering effect and relevance in
      reducing stroke risk and improving outcome are discussed. Finally, based on the
      present information, an evidence-based perspective about current and future use
      of statins in the short- and long-term management of ischemic stroke is
      presented.

PMID- 15853566
TI  - Fuzzy logic and causal reasoning with an 'n' of 1 for diagnosis and treatment of
      the stroke patient.
AB  - The current scientific model for clinical decision-making is founded on binary or
      Aristotelian logic, classical set theory and probability-based statistics.
      Evidence-based medicine has been established as the basis for clinical
      recommendations. There is a problem with this scientific model when the physician
      must diagnose and treat the individual patient. The problem is a paradox, which
      is that the scientific model of evidence-based medicine is based upon a
      hypothesis aimed at the group and therefore, any conclusions cannot be
      extrapolated but to a degree to the individual patient. This extrapolation is
      dependent upon the expertise of the physician. A fuzzy logic multivalued-based
      scientific model allows this expertise to be numerically represented and solves
      the clinical paradox of evidence-based medicine.

PMID- 15853567
TI  - Collateral therapeutics for cerebral ischemia.
AB  - Current therapeutic strategies for acute ischemic stroke focus on vessel
      recanalization or penumbral neuroprotection without consideration of collaterals.
      Collateral circulation defines the extent of the ischemic penumbra, providing
      blood flow to tissues at risk of infarction downstream from an occluded artery.
      Therefore, leptomeningeal collaterals are a principal delivery route for oxygen,
      nutrients and potential therapeutic agents. Understanding of collateral anatomy
      and physiology is essential for the development of effective stroke treatments.
      Diagnostic imaging modalities may illustrate the penumbra from the collateral
      perspective, defining regions of relative ischemic vulnerability. Although
      specific collateral therapeutics are unrealized, insight may be gleaned from
      subtle details of prior stroke studies. Future advances will result from nascent
      research in therapeutic arteriogenesis and gene therapy adapted to the specific
      features of the cerebral circulation.

PMID- 15853568
TI  - Magnetic resonance imaging in the evaluation of intracranial hemorrhage.
AB  - Magnetic resonance imaging is emerging as a valuable tool for the urgent
      evaluation of patients with acute stroke. This review focuses on the applications
      of magnetic resonance imaging in the diagnosis and management of intracranial
      hemorrhage. The biophysical properties of blood in the neuroaxis and the magnetic
      resonance imaging evolution of intracranial bleeding are reviewed. The potential
      applications of magnetic resonance imaging in the evaluation and therapy of
      specific types of intracranial hemorrhage are discussed. Emphasis is made on the
      superiority of magnetic resonance imaging in detecting intracranial hemorrhage
      and ischemic stroke. Although there is some hesitation to perform magnetic
      resonance imaging to evaluate acute intracranial hemorrhage, there is strong
      evidence that magnetic resonance imaging is not inferior to computerized
      tomography in this clinical setting. In the era of acute stroke intervention,
      magnetic resonance imaging offers significant advantages over computed
      tomography.

PMID- 15853569
TI  - Brain imaging in anxiety disorders.
AB  - Animal studies of the effects of stress on the brain have been used as a model
      for anxiety disorders. There is increasing evidence that brain areas involved in
      the stress response, including prefrontal cortex, hippocampus and amygdala, play
      a role in the symptoms of anxiety. In the past few years, brain imaging studies
      have been critical to advancing the understanding of the neural circuitry of
      anxiety disorders. Although some anxiety disorders may fit in with animal models
      of stress, both conceptually and in terms of imaging findings (e.g., post
      traumatic stress and panic disorder), other anxiety disorders (e.g., obsessive
      compulsive disorder) may require a more specific model to understand the
      neurobiology completely. This article reviews animal models for anxiety
      disorders, current brain imaging findings and outlines future directions for
      research in this area.

PMID- 15853570
TI  - Treatments for generalized anxiety disorder.
AB  - Generalized anxiety disorder is characterized by excessive chronic anxiety in
      association with many somatic symptoms. The disorder has pervasive effects on
      quality of life, including work, social and educational aspects and requires long
      term therapy. Available studies in patients are the Diagnostic and Statistical
      Manual of Mental Disorders, third edition-revised and fourth edition, which have
      defined generalized anxiety disorder and demonstrate the efficacy of
      benzodiazepines, azapirones, some antidepressants and psychotherapy.
      Benzodiazepines are effective anxiolytics for short-term use but are accompanied
      by many adverse events. The antidepressants, paroxetine and venlafaxine (Efexor),
      have demonstrated efficacy in patients with generalized anxiety disorder with
      mild side-effect profiles. They have the additional benefit of efficacy in
      depression, which frequently occurs comorbidly in these patients. Long-term
      efficacy has been shown with venlafaxine in the treatment of this chronic
      condition, confirming that as in depression, the goal must not just be remission
      beyond simple symptom resolution but also on to improved functioning and quality
      of life. Psychotherapy with applied relaxation, cognitive therapy and cognitive
      behavioral therapy show the most promise in resolving and maintaining treatment
      gains in the long-term. These approaches may be useful alone or in combination
      with adjunctive pharmacotherapy to achieve remission. Based on current evidence,
      the recommended approach to achieving long-term benefits for patients with
      generalized anxiety disorder is antidepressant therapy with paroxetine or
      venlafaxine in combination with cognitive behavioral therapy.

PMID- 15853571
TI  - Current management of pediatric postoperative pain.
AB  - Pain is a common complaint in children after surgery. Four out of five children
      require analgesia even after minor surgery, and after more extensive surgery,
      significant postoperative pain may last for weeks. Severe pain during, and after
      surgery may aggravate long-lasting negative effects to the body and mind. In
      order to prevent harmful effects, all children should be provided with effective
      analgesia. Pain management should be safe and easy to administer. Postoperative
      pain management in children has improved substantially during the last 5 years.
      Recent trials indicate that children may undergo major surgery with minimal
      untoward effects when effective proactive pain management is provided. This
      review will focus on new clinical strategies on pain management in children.
      Since most pediatric surgery is performed as a day-case or short-stay basic
      recommendations for parental guidance and pain management after discharge are
      also presented.

PMID- 15853572
TI  - Assessment and treatment of disturbed sleep in attention deficit hyperactivity
      disorder.
AB  - Attention deficit hyperactivity disorder affects 3-5% of children in the USA, and
      is commonly accompanied by disrupted sleep in the form of insomnia, restless
      sleep or excessive daytime tiredness. In addition, daytime inattention and
      hyperactivity which mimicks attention deficit hyperactivity disorder can result
      from intrinsic sleep disorders such as obstructive sleep apnea or periodic limb
      movement disorder. In most cases, the correct clinical evaluation permits
      appropriate diagnosis and management. Current research investigating the
      relationship between attention deficit hyperactivity disorder and sleep, as well
      as general precepts of clinical assessment and treatment are reviewed.

PMID- 15853573
TI  - Assessment of dementia in the primary care setting.
AB  - The aging population of the developed world has led to a significant increase in
      the number of people suffering from dementia. Most of these patients are cared
      for in the community by primary care physicians and paramedical staff. However,
      the comprehensive assessment of cognitive changes in an elderly patient is time
      consuming and requires skills that are often lacking in the primary care setting.
      This may lead to misdiagnosis and unnecessary delays in therapeutic intervention.
      In this review, the primary care physician is provided with a structured approach
      to the assessment of cognitive decline.

PMID- 15853574
TI  - Cluster headache: from vascular theories to brain therapy.

PMID- 15853576
TI  - Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors
      for MS.
AB  - Natalizumab (Antegren, Elan Corp. plc.; Biogen Idec.) is the first alpha4
      integrin antagonist in the class of selective adhesion molecule inhibitors and is
      in Phase III clinical trials for the treatment of multiple sclerosis. After a 300
      mg intravenous infusion, natalizumab has an elimination half-life of 6 to 9 days,
      but alpha4-integrin receptors expressed on the surface of peripheral blood
      leukocytes are more than 80% saturated approximately 1 month postinfusion.
      Therefore, natalizumab is given as a 300 mg dose administered monthly.
      Preliminary efficacy results showed a marked reduction (approximately 90%) in the
      formation of new gadolinium-enhancing lesions and reduced the number of patients
      with relapse by 50% in patients with relapsing-remitting or secondary progressive
      multiple sclerosis receiving natalizumab versus those receiving placebo over a 6
      month period. In clinical studies, natalizumab has demonstrated a favorable
      safety profile. Pivotal Phase III studies of natalizumab as monotherapy and in
      combination with intramuscular interferon-beta-1a are underway in patients with
      relapsing-remitting multiple sclerosis. Natalizumab may be an important addition
      to the therapeutic armamentarium for multiple sclerosis.

PMID- 15853577
TI  - Ropinirole therapy for Parkinson's disease.
AB  - Ropinirole (Requip, GlaxoSmithKline) is a novel nonergoline dopamine D2 agonist
      indicated for the treatment of early and advanced Parkinson's disease. It is
      mainly metabolized by the liver and its elimination half-life is approximately
      5.8 h. When used as monotherapy in early Parkinson's disease, ropinirole improves
      signs and symptoms of the disorder. When used as an adjunct to levodopa in
      advanced Parkinson's disease patients with motor fluctuations, ropinirole reduces
      off time and allows a reduction of levodopa dose. The initial use of ropinirole
      in early Parkinson's disease to which levodopa is added when necessary, has been
      demonstrated to lead to a lower incidence of dyskinesias compared with treatment
      with levodopa alone. An 18F-dihydroxyphenylalanine positron emission tomography
      study suggested the possibility that ropinirole could slow the progression of
      loss of dopamine neurons compared with treatment with levodopa but this remains
      to be proven. Side effects of ropinirole include nausea, somnolence, edema,
      orthostatic hypotension, hallucinations and dyskinesia. A once-daily formulation
      of ropinirole is currently in development that has the potential for greater
      convenience, improved tolerability and greater efficacy.

PMID- 15853578
TI  - Clinical experience with the novel levodopa formulation entacapone + levodopa +
      carbidopa (Stalevo).
AB  - Levodopa is the main pharmacologic treatment for Parkinson's disease. However,
      the long-term administration of levodopa is associated with the development of
      motor complications which can seriously compromise patient function. Increasing
      evidence indicates that such problems are related to abnormal pulsatile
      stimulation of striatal dopamine receptors and that treatments providing more
      continuous stimulation reduce the risk of motor complications. It is possible
      that administering levodopa with a reversible catechol-O-methyl transferase
      inhibitor at frequent intervals might reduce the risk of these complications.
      Stalevo (Orion) combines levodopa, the dopa-decarboxylase inhibitor carbidopa and
      the catechol-O-methyl transferase inhibitor entacapone in a single tablet. This
      review provides an overview of the initial clinical experience gained with
      Stalevo during clinical trials, including several case studies.

PMID- 15853579
TI  - Atomoxetine in the treatment of attention deficit hyperactivity disorder.
AB  - Atomoxetine (Strattera, Eli Lilly & Co.) is a highly selective noradrenaline
      reuptake inhibitor and the first nonstimulant medication to be approved for the
      treatment of attention deficit hyperactivity disorder. Currently, nine published
      clinical trials have documented the safety and efficacy of atomoxetine in the
      treatment of children, adolescents and adults with attention deficit
      hyperactivity disorder and data presented throughout the past year at national
      scientific meetings has further addressed its utility. This article reviews the
      available information on atomoxetine, accompanied by a discussion of its clinical
      use.

PMID- 15853580
TI  - Clinical application of C-reactive protein in stroke prevention: bright and dark
      sides of the moon.
AB  - In different study populations, several studies have shown that modest C-reactive
      protein elevation, in the range of apparently healthy individuals, is a strong
      predictor of future vascular events. Willcox and colleagues summarize the
      epidemiological and clinical observations that have led to the enthusiastic
      suggestion that determination of serum C-reactive protein levels could also be
      used as an adjunct for risk assessment in primary and secondary prevention of
      cerebrovascular disease. Currently, high-sensitivity C-reactive protein assays as
      a screening test to ascertain individuals at risk of cerebrovascular disease does
      not provide an accurate determination of the risk of stroke likelihood, and
      adequate evidence that early detection improves health outcomes and that an early
      intervention is likely to have a beneficial impact. High-sensitivity C-reactive
      protein assays as a screening test, only provide inadequate evidence to be
      considered as an effective cerebrovascular screening test, especially in the
      elderly.

PMID- 15853581
TI  - Aggression and disruptive behavior disorders in children and adolescents.
AB  - Aggression is a common symptom of many psychiatric disorders including attention
      deficit hyperactivity disorder, oppositional defiant disorder, conduct disorder,
      Tourette's disorder, mood disorders (including bipolar disorder), substance
      related disorders, alcohol-related disorders, mental retardation, pervasive
      developmental disorders, intermittent explosive disorder and personality
      disorders (particularly antisocial personality disorder). Many forms of organic
      brain disorders may present with aggressive behavior. Aggression is common in
      some epileptic patients and some endocrinological diseases (e.g., diabetes and
      hyperthyroidism) may be associated with aggressive behavior. Physicians need to
      rule out many medical and psychiatric disorders before diagnosing aggressive
      behavior. A thorough diagnostic work up is the most important step in determining
      the nature of comorbid disorders associated with the behavioral problem.
      Structured interviews and rating scales completed by patients, parents, teachers
      and clinicians may aid the diagnosis and provide quantification for the change
      process related to treatment. The integration of medication, individual and
      family counseling, educational and psychosocial interventions including the
      school and community, may increase the effectiveness of interventions. Due to the
      common association of aggression and disruptive behaviors with attention deficit
      hyperactivity disorder, psychostimulants including new generation long-acting
      medications and other nonstimulant medications are considered the drug of choice
      for managing aggressive behavior and disruptive behavior disorders. Severe
      aggressive behavior not responding to these medications may require the single or
      combined use of mood regulators including lithium and/or antispychotic
      medications. Drugs such as risperidone (Risperdal, Janssen-Cilag) have documented
      effectiveness and safety in children and adolescents, and can be used in
      treatment.

PMID- 15853582
TI  - Metastases to the brain: current management perspectives.
AB  - Brain metastases are ten-times more common than primary brain tumors and are a
      common complication in patients with systemic cancer. The most common sources of
      brain metastases are lung and breast cancers, although in 15% of patients, the
      primary site is unknown. Optimal treatment is dependant upon tumor location,
      size, number of tumors and status of the systemic disease. Currently, management
      of brain metastases with surgery, radiotherapy and stereotactic radiosurgery is
      known to improve the quality of life and even life expectancy for selected
      patients. Techniques under investigation include focal radiation techniques,
      magnetic resonance imaging guided thermal ablation of metastases, drug delivery
      modes that bypass the blood-brain barrier and novel drug and molecular
      therapeutics. Efforts are ongoing to understand the molecular biology of brain
      metastases.

PMID- 15853583
TI  - Intracranial meningiomas: diagnosis and treatment.
AB  - Meningiomas are extra-axial CNS tumors which have a female predominance and occur
      in middle-to-late adult life. Most meningiomas (90%) are benign, 6% are atypical
      and a small proportion (2%) are malignant. Most patients diagnosed with a
      meningioma undergo surgical resection to relieve neurological symptoms. Complete
      surgical resection is often curative. For most incompletely resected or recurrent
      tumors not previously irradiated, radiotherapy is administered. Radiotherapy may
      be administered as either conventional external beam irradiation or
      stereotactically by linear accelerator, gamma knife or cyberknife radiosurgery.
      Advocates of stereotactic radiotherapy have suggested this therapy in lieu of
      surgery particularly in poor surgical risk patients, patients with meningiomas in
      eloquent or surgically inaccessible locations and in patients of advanced age.
      When the meningioma is unresectable or all other treatments (e.g., surgery and
      radiotherapy) have failed, hormonal chemotherapy may be considered.
      Notwithstanding limited data, hydroxyurea has been modestly successful in
      patients with recurrent meningiomas.

PMID- 15853584
TI  - Delivery systems and molecular targets of mechanism-based therapies for GBM.
AB  - Glioblastoma multiforme (GBM) is the most common malignant brain tumor of adults
      and is in great need of novel diagnostic and therapeutic approaches. Diagnosis is
      beginning to consider a tumor's genetic status and in the future may incorporate
      gene expression or proteomic profiles. Genetic alterations in gliomas that are
      being used in classification include TP53 and retinoblastoma pathway disruption,
      PTEN mutations, epidermal growth factor receptor amplification and 1p/19q losses.
      Molecular mechanisms are being exploited to treat glioblastoma multiforme.
      Tyrosine kinase inhibitors directed at epidermal growth factor receptor (ZD1839,
      OSI-774) are being explored. Farnesyltransferase inhibitors (R115777) block
      activation of the ras pathway and may be effective. Antagonists of the endothelin
      receptor (e.g., atrasentan) expressed on blood vessels may block the high degree
      of angiogenesis in gliomas. Tumors lacking methylthioadenosine phosphorylase are
      sensitive to inhibitors of de novo adenosine synthesis (SDX-102) since they lack
      a salvage pathway. Future goals are to tailor therapies to a tumor's molecular,
      proteomic or genomic status ,and manage glioblastoma multiformes as in chronic
      diseases in a multidisciplinary clinical setting.

PMID- 15853585
TI  - Neuroimaging in glioma therapy.
AB  - The introduction of computed tomographic and magnetic resonance imaging into
      clinical practice is among the most important of all advances in the care of
      patients with brain tumors. Diffuse astrocytomas of the adult cerebral
      hemispheres are unique among human tumors for the degree to which their imaging
      features correlate with pathologic characteristics and clinical behavior.
      However, there is still little understanding of the value of various imaging
      features in measuring response and progression in brain tumors. This review
      focuses on some of the unsolved problems in the use of neuroimaging in measuring
      the response of brain tumors to therapy.

PMID- 15853586
TI  - Safety and efficacy of outpatient gamma knife radiosurgery for multiple cerebral
      metastases.
AB  - This review highlights the experience of a single institution using the Leksell
      gamma knife for 8 years. More than 500 patients with multiple cerebral metastases
      received outpatient radiosurgery. The results prove that there is a high efficacy
      and attractively low morbidity of modern outpatient radiosurgery. When compared
      with whole brain radiation therapy, radiosurgery improved survival in patients
      with cerebral metastases. Most importantly, the number of brain metastases had no
      prognostic impact in patients with non-small cell lung cancer, renal cell cancer,
      malignant melanoma and gastrointestinal cancer.

PMID- 15853587
TI  - Current approaches to CNS tumors in infants and very young children.
AB  - Treatment of infants and very young children with tumors of the CNS is
      challenging due to the vulnerability of the developing nervous system.
      Historically, treatment has relied upon surgery and radiation for control of
      malignant tumors with limited success and severe long-term consequences in most
      young patients. More recent studies have attempted to utilize chemotherapy and
      second-look surgery in attempts to reduce, delay or avoid radiation.
      Identification of prognostic factors for specific tumor types may distinguish
      which patients should receive more aggressive therapies and which patients can
      potentially avoid them and their potential side effects. Achieving successful
      tumor control while optimizing quality of life for survivors is the major goal of
      recent research.

PMID- 15853588
TI  - Treatment of malignant gliomas: radiotherapy, chemotherapy and integration of new
      targeted agents.
AB  - Progress in the biological and molecular characterization of gliomas and studies
      of factors associated with tumor growth and progression have led to translational
      research projects and the development of rational new approaches regarding
      prognostic models, better prediction of response to treatment and innovative
      therapeutic strategies. This review summarizes the available data on established
      and emerging prognostic factors and prognostic scores, and discusses their
      limitations as well as their potential influence on future therapeutic efforts.
      Recent developments in standard treatment options (i.e., surgery, radiotherapy
      and chemotherapy) are reviewed. Experimental data indicate that inhibition of
      several signaling pathways (e.g., epidermal growth factor, transforming growth
      factor-beta and phosphatidylinositol 3 kinase) may represent a promising
      therapeutic strategy. Some inhibitory agents (i.e., drugs, antibodies and
      antisense oligonucleotides) have now entered clinical trials, mainly for
      recurrent gliomas and a small number are being tested in combination with
      radiotherapy. Early results of such approaches are presented.

PMID- 15853589
TI  - Pharmacological treatment strategies for schizophrenia.
AB  - The pharmacological choices for the treatment of schizophrenia have been greatly
      expanded with the availability of the atypical compounds clozapine (Clozaril,
      Novartis), risperidone (Risperdal, Janssen-Cilag), olanzapine (Zyprexa, Eli Lilly
      & Co.), quetiapine (Seroquel, AstraZeneca), ziprasidone (Geodon, Pfizer Inc.) and
      aripiprazole (Abilify, Otsuka Pharmaceutical Co. Ltd). In this article, the
      effects of the newer antipsychotics and their side effects are reviewed. Key
      issues in acute and maintenance treatment, often lifelong, will be reviewed. Side
      effect management to ensure adherence to an optimal treatment regimen will be
      discussed. Coexisting syndromes must be treated in concordance with the patient's
      clinical presentation. For treatment-resistant patients, atypical compounds are
      generally more effective than their typical counterparts but medication
      augmentation strategies are frequently recommended. Finally, the results of
      recent meta-analyses comparing the effects of atypical versus typical compounds
      will be critically reviewed and remaining gaps in the current pharmacotherapy of
      schizophrenia will be explored.

PMID- 15853590
TI  - Genetics of schizophrenia: implications for treatment.
AB  - Schizophrenia is a common, debilitating illness for which treatment is empirical
      and unsatisfactory. Intense efforts to identify etiological factors have been
      launched in order to facilitate rational therapy. Such efforts have included gene
      mapping studies since a significant heritability has been proved. In common with
      other polygenic/multifactorial disorders, mapping efforts for schizophrenia pose
      daunting challenges. Faced with such complexities, attempts to detect genetic
      associations with pharmacological response have been initiated. Although
      intriguing associations have been reported, formal replication is required.
      Suggestions for the design of replicate studies are proposed. This review is
      restricted to studies that investigated response to clozapine (Clozaril,
      Novartis) and other novel antipsychotic medications.

PMID- 15853591
TI  - Adiposopathy: role of adipocyte factors in a new paradigm.

PMID- 15853593
TI  - Tirofiban in acute coronary syndromes.
AB  - Acute coronary syndromes represent a major health problem in terms of incidence
      and mortality. Intracoronary platelet-rich thrombi may develop in response to
      plaque rupture, and are involved in the pathogenesis of all acute coronary
      syndromes. The glycoprotein IIb/IIIa receptor, a platelet surface integrin, plays
      a key role in platelet aggregation once it has been activated by specific
      ligands. The development of glycoprotein IIb/IIIa inhibitors has revolutionized
      the management of acute coronary syndromes. Tirofiban is one of three parenteral
      glycoprotein IIb/IIIa inhibitors in clinical use, and many trials have
      demonstrated its clinical efficacy and low rate of adverse effects in patients
      with non-ST-segment elevation acute coronary syndrome. This article reviews the
      data concerning its use in the clinical settings of acute coronary syndromes and
      percutaneous coronary angioplasty, and discusses its benefits in different
      treatment strategies and in association with other drugs. In particular, the role
      of early, upstream tirofiban coupled with early aggressive revascularization in
      the management of high-risk non-ST-segment elevation acute coronary syndromes is
      emphasized.

PMID- 15853594
TI  - Barnidipine: a new calcium channel blocker for hypertension treatment.
AB  - Although it is commonly agreed that all antihypertensive medications have similar
      efficacy, there are important differences related to safety, tolerability,
      patient adherence, cost effectiveness and effects on the prevention or
      retardation of associated disease progression. It is desirable for
      antihypertensives to have a long duration of action so that once-daily dosing is
      possible. In addition, antihypertensive medication must be able to be
      administered concomitantly with other drugs likely to be taken by the patients.
      This is particularly critical in the elderly population. Barnidipine, a novel,
      long-acting calcium antagonist, has met these challenges of modern
      pharmacotherapy. Its once-daily dosing, good tolerability and durable
      antihypertensive effect contribute to excellent patient adherence and make this
      drug a valuable addition to the antihypertensive formulary.

PMID- 15853595
TI  - Iloprost for idiopathic pulmonary arterial hypertension.
AB  - Idiopathic pulmonary arterial hypertension is a rare but serious and life
      threatening disease that leads to right heart failure and death within 2.8 years
      without specific treatment. This review focuses on the stable prostacyclin analog
      iloprost, its biologic action and pharmacology and, finally, on its clinical
      development, efficacy and safety in patients with idiopathic pulmonary arterial
      hypertension, which led to its approval for this indication. Furthermore, this
      review assesses the role of iloprost compared with other newly developed drugs,
      such as the endothelin receptor antagonist bosentan and the phosphodiesterase-5
      inhibitor sildenafil, as well as other modes of application of prostacyclin and
      its analogs for the treatment of idiopathic pulmonary arterial hypertension.
      Based on the different modes of action of these substances, a combination of
      these treatments could be most promising for the future.

PMID- 15853596
TI  - Management of obesity cardiomyopathy.
AB  - Obesity causes a variety of hemodynamic alterations that may lead to changes in
      cardiac structure and function. Although such abnormalities may occur in patients
      with mild-to-moderate obesity, they are most pronounced in those with morbid
      obesity. When these alterations produce congestive heart failure, obesity
      cardiomyopathy is said to be present. In this review, the authors will first
      discuss the pathogenesis and clinical manifestations of obesity cardiomyopathy
      and then describe the management of this clinical syndrome with emphasis on the
      effects of weight reduction.

PMID- 15853597
TI  - Lifestyle modification and endothelial function in obese subjects.
AB  - The metabolic syndrome is a cluster of metabolic and vascular abnormalities that
      include central obesity, insulin resistance, hyperinsulinemia, glucose
      intolerance, hypertension, dyslipidemia, hypercoagulability and an increased risk
      of coronary and cerebral vascular disease. These metabolic and vascular
      abnormalities are the main cause of cardiovascular mortality in western
      societies. Endothelial dysfunction, an early step in the development of
      atherosclerosis, has been reported in obese nondiabetic individuals and in
      patients with Type 2 diabetes. It has also been observed in individuals at high
      risk for Type 2 diabetes, including those with impaired glucose tolerance and the
      normoglycemic first-degree relatives of Type 2 diabetic patients. Recent evidence
      points to adipocytes as a complex and active endocrine tissue whose secretory
      products, including free fatty acids and several cytokines (i.e., leptin,
      adiponectin, tissue necrosis factor-alpha, interleukin-6, and resistin) play a
      major role in the regulation of human metabolic and vascular biology. These
      adipocytokines have been claimed to be the missing link between insulin
      resistance and cardiovascular disease. Interventions designed to improve
      endothelial and/or adipose-tissue functions may reduce cardiovascular events in
      obese individuals with either the metabolic syndrome or Type 2 diabetes.
      Lifestyle modification in the form of caloric restriction and increased physical
      activity are the most common modalities used for treating those individuals at
      risk and is unanimously agreed to be the initial step in managing Type 2
      diabetes. Several recent studies have demonstrated favorable impacts of lifestyle
      modifications in improving endothelial function and insulin sensitivity, in
      addition to altering serum levels of adipocytokines and possibly reducing
      cardiovascular events. This review discusses current knowledge of the role of
      lifestyle modifications in ameliorating cardiovascular risk in obese subjects
      with either the metabolic syndrome or Type 2 diabetes.

PMID- 15853598
TI  - Diabetes and obesity: new data on mechanisms and intervention trials.
AB  - The increase in obesity and Type 2 diabetes on a global scale has heightened
      interest in how to counteract this epidemic. Improved lifestyle is a fundamental
      approach but other remedies, such as drugs and surgery, have also been tested.
      One question requiring further research is what happens after weight loss.
      Ongoing studies will try to address this question, including the Swedish Obese
      Subjects (SOS) study, and the Look Action for HEAlth in Diabetes (Look AHEAD)
      trial in the USA, the latter looking at obese Type 2 diabetes patients.

PMID- 15853599
TI  - Role of surgical revascularization in diabetic patients with coronary artery
      disease.
AB  - Diabetes is a well-known risk factor for morbidity and mortality associated with
      coronary artery disease. Currently, diabetics represent approximately a quarter
      of patients requiring coronary revascularization in the USA. The purpose of this
      article is to review and analyze the available data in surgical revascularization
      of diabetic patients with coronary artery disease. The review will also examine
      new developments in myocardial revascularization and assess their probable impact
      on the long-term outcome of diabetic patients.

PMID- 15853600
TI  - Role of stents in congenital heart disease.
AB  - For more than 10 years, balloon-expandable intravascular stents have become an
      integral part of treatment for obstructive vascular lesions in children and
      adults with congenital heart disease. The initial problems with stents, such as
      sharp edges, rigid frame and unacceptable shortening when over-expanded have been
      overcome to a large extent with the newer designs. The problems related to
      delivery of stents, such as stent migration, balloon rupture, flaring of the
      edges of the stent, rupture of vessels and milking of the stent off the balloon,
      have also been overcome by newer designs of balloons. The failure of growth of
      balloon-expandable stents with the growth of the child is managed by redilation
      with or without additional stenting and newer growth stents. Self-expanding
      stents are not appropriate for use in growing children due to the limitation of
      their maximum diameters. The development of biodegradable stents may overcome
      these disadvantages in the future. Various new developments have recently
      occurred. Covered stents are ideal for treating acute vessel rupture and in
      isolating vascular aneurysms. Drug-eluting stents may prevent restenosis, but
      have not been used in children. Valved stents are a recent innovation for the
      treatment of regurgitant pulmonary valves.

PMID- 15853601
TI  - Mitral regurgitation: overview of current surgical techniques and future
      developments.
AB  - Mitral regurgitation is a complex disease with many different etiologies,
      underlying dysfunctions and histologic alterations. Surgical correction of this
      condition dramatically improves the life expectancy and life quality of affected
      patients. The structure of the mitral valve lends itself to many surgical
      techniques. The purpose of this review is to offer readers an overview on this
      subject.

PMID- 15853602
TI  - Left-ventricular aneurysms: from disease to repair.
AB  - Myocardial infarction may be complicated by the formation of a left-ventricular
      aneurysm that distorts the normal elliptical geometry of the ventricle to produce
      a dilated spherical ventricle with limited contractile and filling capacities.
      One of the consequences is congestive heart failure, which may be refractory to
      medical therapy and require surgical treatment. Surgical methods to restore the
      volume and shape of the left ventricle have evolved over the years. Nevertheless,
      although surgery for left-ventricular aneurysms has been performed for almost 50
      years, the most appropriate approach is still controversial. This review gives an
      overview of the postinfarction left-ventricular aneurysm, tackling issues from
      the disease itself to surgical and other techniques of ventricular remodeling.

PMID- 15853603
TI  - Bicuspid aortic valve disease: recent insights in pathophysiology and treatment.
AB  - Bicuspid aortic valve is a common congenital cardiac malformation with a broad
      spectrum of clinical outcomes. Bicuspid aortic valve may go undetected throughout
      an individual's lifetime or, alternatively, they may have devastating clinical
      consequences, resulting in death. Both clinicians and medical scientists have
      taken a renewed interest in the development, pathophysiology and treatment
      options for this subtle but often substantial clinical entity. Evidence is
      mounting to suggest that an underlying disease of the aorta is inherited with
      bicuspid aortic valve, although considerable controversy surrounds this theory.
      Novel molecular mechanisms underlying the valve and vascular pathologies, as well
      as new surgical therapies for these patients have been proposed in the past 10
      years.

PMID- 15853604
TI  - Advances in cardiac magnetic resonance imaging and computed tomography.
AB  - Imaging evaluation of the heart encompasses structural evaluation of the
      chambers, valves and coronary arteries, and functional evaluation, including
      assessment of perfusion, wall motion and myocardial viability. Magnetic resonance
      imaging is well established for the structural and functional evaluation of the
      heart, and benefits from direct multiplanar image acquisition and a lack of
      ionizing radiation. Magnetic resonance imaging assessment of myocardial viability
      after myocardial infarction appears to be helpful in predicting benefit from
      revascularization procedures. Magnetic resonance imaging continues to hold
      promise as the least invasive method of coronary artery evaluation, and
      continuing developments are improving image quality and decreasing examination
      time. The development of cardiac-gating techniques for multidetector computed
      tomography has the potential to provide widespread availability of cardiac
      computed tomography. Short examination times and straightforward scanning
      procedures promise a convenient method for the examination of cardiac structure
      and function. However, this convenience must be balanced against radiation dose
      and contrast-media requirements when determining the appropriate use of cardiac
      computed tomography. Computed tomography coronary-calcium scoring can aid in the
      prediction of significant coronary events in all but the lowest-risk patients.
      The high negative-predictive value of computed tomography coronary angiography
      may allow some patients to avoid cardiac catheterization, but its role in the
      assessment of patients with moderate coronary atherosclerosis remains unclear.
      New software tools can assist in the complex and tedious analysis of the large
      volumes of data produced by these examinations.

PMID- 15853605
TI  - Renal angioplasty and stenting: long-term results and the potential role of
      protection devices.
AB  - Renal angioplasty and stenting have become the first treatments to be proposed to
      patients presenting with renal artery stenosis. The immediate technical success
      rate is high, with a low complication rate and good long-term patency. In most
      reports, renal stenting has been proven to improve blood pressure. However,
      despite good immediate- and long-term results, postprocedural deterioration of
      renal function is a concern, and may occur after renal artery angioplasty and
      stenting in 20 to 40% of patients, which limits the immediate benefits of this
      technique. Of the causes of this deterioration in renal function, atheroembolism
      seems to play an important role. Contrary to earlier beliefs that
      atheroembolization is not an issue during percutaneous catheter interventions,
      there is now mounting evidence that distal atherosclerotic debris commonly
      embolizes from lesions in many vascular territories during percutaneous
      interventions. Atheroembolism seems to be the root cause of many procedural
      complications wherever atherosclerotic lesions are treated. Distal embolization
      was first demonstrated in saphenous vein grafts and now, clinical data are
      proving that similar embolization and distal-organ complications also occur
      during catheter treatment in certain native coronary lesions, carotid stenting
      and renal artery stenting, demonstrating the role and efficacy of protection
      devices to reduce the incidence of end-organ complications. The same protection
      devices (protection balloon and filters) utilized for coronary or carotid
      procedures may be used to protect the kidney from atheroembolism. In this review,
      the authors discuss recently published data concerning the techniques and results
      of renal angioplasty and stenting procedures performed under protection, and
      evaluate the benefits of this technique on renal function and its role in the
      future. Indications for this technique need to be discussed.

PMID- 15853606
TI  - Diagnosis and management of heparin-induced thrombocytopenia.
AB  - Heparin use is ubiquitous, wherein 1 to 5% of patients exposed to standard
      unfractionated heparin develop thrombocytopenia due to antibodies to a complex of
      heparin and platelet factor 4. Classic features include onset of thrombocytopenia
      after 5 to 10 days of ongoing heparin exposure, a 50% fall in the platelet count
      from baseline, resolution of the thrombocytopenia 5 to 10 days after cessation of
      heparin and a high risk of thrombosis noted in 30 to 75% of patients with heparin
      induced thrombocytopenia (HIT) in terms of every-other-day platelet-count
      monitoring in patients on standard unfractionated heparin. And those patients
      developing thrombocytopenia necessitate an accurate, readily accessible
      diagnostic test for HIT. Diagnosis has been recently facilitated by the
      development of an enzyme-linked immunosorbent assay (ELISA) test for the heparin
      P4 antibody complex, although this test carries a relatively low specificity.
      Widespread use of the ELISA demonstrates a relatively high prevalence of the
      antibody in patients exposed to heparin in certain settings, such as
      cardiopulmonary bypass, wherein a quarter of patients have a positive ELISA of
      unclear significance. Once HIT is diagnosed, the high risk of thrombosis
      necessitates empiric anticoagulation with an antithrombin such as argatroban or
      lepirudin, or the heparinoid danaparoid. Additional agents under further study
      include the antithrombin bivalirudin and the pentasaccharide fondaparinux. Future
      issues in HIT include increasing awareness for HIT, improving the specificity of
      HIT testing and the development of new anticoagulants for HIT that will enable
      out-patient management.

PMID- 15853607
TI  - Medical therapeutics for pulmonary arterial hypertension: from basic science and
      clinical trial design to evidence-based medicine.
AB  - Pulmonary arterial hypertension is a severe disease with poor prognosis, caused
      by obliteration of the pulmonary vasculature as a result of pulmonary-vascular
      remodeling, active vasoconstriction and in situ thrombosis. Left untreated,
      pulmonary arterial hypertension results in right-ventricular failure and death.
      There has been dramatic progress in the treatment of pulmonary arterial
      hypertension during recent years. A remarkable number of randomized-controlled
      trials with agents known to target specific abnormalities present in pulmonary
      arterial hypertension have been completed. Most commonly, therapeutic efficacy
      was judged by the ability of the drug under study to improve exercise capacity
      and to decrease the rate of severe complications. Completed clinical trials have
      mainly evaluated patients with relatively advanced disease. Despite these
      advances, responses to therapy in pulmonary arterial hypertension are not
      uniformly favorable and frequently incomplete. In addition, the methods of
      delivery and the adverse effect profile of the currently available pulmonary
      arterial hypertension-specific drugs create further management difficulties.
      Based on newly identified pathobiologic abnormalities in the pulmonary
      vasculature, future studies are likely to focus on the discovery of new
      therapeutic targets. Clinical trial design will continue to evolve in an attempt
      to enable inclusion of patients with less advanced disease and evaluation of
      treatment combinations or comparisons of the currently approved drugs.

PMID- 15853610
TI  - Donepezil (Aricept) for treatment of Alzheimer's disease and other dementing
      conditions.
AB  - Alzheimer's disease is common, incurable and disabling. It is expected to grow
      dramatically in prevalence over the next 50 years. At current, the standard of
      care for patients with mild and moderately severe Alzheimer's disease includes
      the use of acetylcholinesterase inhibitors. Donepezil (Aricept) is a highly
      selective acetylcholinesterase inhibitors with a pharmacokinetic profile allowing
      once-daily dosing. There is an extensive knowledge base derived from published
      clinical trials of donepezil in Alzheimer's disease, revealing consistent
      efficacy in cognition, global clinical ratings and daily function. Donepezil is
      also associated with additional meaningful outcomes such as reduced risk for, or
      delay to, nursing home placement. Despite a sense of limited efficacy of this
      drug class among prescribers, number needed-to-treat analyses suggest donepezil
      is highly effective at reducing the long-term adverse outcomes associated with
      Alzheimer's disease.

PMID- 15853611
TI  - Mitoxantrone (Novantrone) in multiple sclerosis: new insights.
AB  - The conclusions of a recent study of mitoxantrone (Novantrone) in multiple
      sclerosis and the approval of several health authorities support its use in
      patients with active relapsing-remitting or secondary progressive multiple
      sclerosis. This drug profile provides an outline on relevant preclinical and
      clinical studies, discusses relevant side effects of the compound and places
      mitoxantrone in the context of other therapeutic approaches available against
      this disabling disorder.

PMID- 15853612
TI  - Botulinum toxin type A (Botox) in the treatment of migraine and other headaches.
AB  - Botulinum toxin type A (Botox) is increasingly used in the management of migraine
      and tension-type headaches. The results from small placebo-controlled trials and
      extensive open-label experience has suggested a significant role for this
      neurotoxin in the management of refractory headache. Several large placebo
      controlled trials of episodic and chronic migraine are currently underway.

PMID- 15853613
TI  - Zolmitriptan (Zomig).
AB  - New triptans are being released in rapid succession with each addition
      demonstrating some specific pharmacokinetic properties, which may be translated
      into clinical advantages. Zolmitriptan (Zomig) offers a range of alternatives to
      migraine sufferers. The conventional tablet is consistently effective across a
      wide range of migraine subtypes. The orally disintegrating tablet offers an
      effective option for those migraineurs who are nauseated or need to take their
      medication earlier in the course of their migraine. Since it can be taken without
      fluid, the orally disintegrating tablet may be consistently used early in the
      migraine attack when the pain is still mild. The nasal spray aggregates all the
      benefits of the oral formulations and has a faster onset of action. The 5-mg dose
      of all three forms of zolmitriptan offers additional benefits over the 2.5-mg
      dose at early time points. The physician can now choose the optimum route of
      delivery of zolmitriptan to stop the headache, increase the likelihood of
      reducing disability and restore the patient to complete functionality.

PMID- 15853614
TI  - Verbal memory deficit in patients with schizophrenia: an important future target
      for treatment.
AB  - Despite more than two-thirds of patients with schizophrenia showing reductions in
      delusions and hallucinations following optimum available treatment, many are left
      with crippling cognitive impairments. Neurocognitive deficit is a core feature of
      schizophrenia, but the question arises as to whether efforts should be geared
      towards ameliorating and normalizing these deficits. Verbal memory dysfunction is
      one of the most consistently reported cognitive deficits and among the best
      predictors of functional outcome in schizophrenia. Therefore, a better
      understanding of the nature of this deficit could lead to treatments that not
      only improve the specific systems mediating the impairment, but could also have
      wider implications for clinical and social outcome.

PMID- 15853615
TI  - Pharmacologic treatment of adolescent and child schizophrenia.
AB  - Although relatively rare in childhood, the incidence of schizophrenia increases
      in adolescence. Compared with adult-onset schizophrenia, there are differences in
      the response to various psychopharmacologic agents and an urgent need for more
      clinical treatment trials in child-onset schizophrenia. The history, epidemiology
      and clinical presentation of early- and very early-onset schizophrenia is
      reviewed with a focus on the available pharmacologic treatment literature.
      Information on the older typical antipsychotics, newer atypical antipsychotics
      and most promising new potential agents, their benefits and pitfalls are
      summarized. Acute management as well as continuation and maintenance therapy
      recommendations are made.

PMID- 15853616
TI  - Course of cognitive functioning in first episode schizophrenia spectrum
      disorders.
AB  - Studies of cognitive functioning in patients with first episode schizophrenia
      spectrum disorders can be particularly informative. Through the use of electronic
      and bibliography-based searches, the authors identified studies examining the
      course of cognitive functioning in first episode patients. The results of this
      review indicated that first episode patients at presentation for treatment often
      show compromised cognitive functioning, particularly in the domains of verbal
      learning and memory, psychomotor speed and attention. However, in comparison with
      patients with a longer illness history, first episode patients demonstrate
      significantly superior performance. In longitudinal studies of first episode
      patients, cognitive functioning generally remained static, suggesting limited
      change in performance over the first several years of the illness. The
      implications of these findings for future research are discussed.

PMID- 15853617
TI  - Review of magnetic resonance imaging and spectroscopy studies in children with
      bipolar disorder.
AB  - Pediatric bipolar disorder is a serious condition that affects a child's ability
      to function normally during important developmental stages. Pediatric bipolar
      disorder often presents with a different symptom complex than adult-onset bipolar
      disorder, including higher rates of irritability and rapid cycling. Due to these
      differences, it is important to understand the neural substrates of the disease
      as it presents in children, especially when compared with adults. Understanding
      the brain abnormalities associated with pediatric bipolar disorder may provide
      much needed markers useful in diagnosing childhood-onset bipolar disorder, give
      insight into the neurobiological etiology of the disorder and lead to more
      effective treatments. Currently, there has been little neuroimaging research into
      pediatric bipolar disorder, specifically with regards to brain function. This
      review summarizes the neurobiological research that has been conducted on
      childhood- and adolescent-onset bipolar disorder using magnetic resonance
      technology. Future directions of research needed in this area also are discussed
      in the context of the existing literature.

PMID- 15853618
TI  - Insulin-like growth factor I and Alzheimer's disease: therapeutic prospects?
AB  - The search for a cure of Alzheimer's dementia is restless. In recent years,
      unexpected epidemiological data showing a protective effect of anti-inflammatory
      and cholesterol-lowering drugs gave way to clinical trials with these compounds.
      Now, a newly described mechanism indicating that brain amyloid clearance is
      modulated by serum insulin-like growth factor I may also lead to new trials with
      this growth factor. Insulin-like growth factor I is an abundant circulating
      hormone with potent central actions whose levels in serum appear to be altered in
      Alzheimer's patients. Amyloid clearance, a potential therapeutic target in
      Alzheimer's disease was mostly neglected until recent antiamyloid therapies
      proved to involve a peripheral amyloid sink. Although more work in animal models
      are required, the evidence available strongly indicates that insulin-like growth
      factor I therapy in Alzheimer's dementia may be addressing pathogenic processes.

PMID- 15853619
TI  - Angiotensin and Alzheimer's disease: therapeutic prospects.
AB  - This review describes the features of Alzheimer's disease and discusses the
      evidence that antihypertensive therapies may be beneficial in its treatment and
      prevention. Drugs acting via the renin-angiotensin system are considered and it
      is suggested that these drugs may produce their effects via mechanisms other than
      by their antihypertensive actions. Using evidence from animal studies, the role
      of angiotensin as a neurotransmitter and its involvement in the control of normal
      cognitive function is described. Studies of angiotensin and human cognition are
      reviewed along with studies investigating the possible link between disorders of
      the system, either inherited or acquired, and the symptoms of Alzheimer's
      disease. The therapeutic potential of screening for markers of renin-angiotensin
      abnormality for the prediction of Alzheimer's disease is considered, as is the
      potential use of agents known to influence the renin-angiotensin system in the
      treatment or prevention of the disease.

PMID- 15853620
TI  - Novel ventriculo-peritoneal shunt in Alzheimer's disease cerebrospinal fluid
      biomarkers.
AB  - Alzheimer's disease is an age-related dementia and its incidence is rising in
      developed countries as the population ages. Amyloid plaques and tau-rich
      neurofibrillary tangles are pathologic hallmarks of the disease. Treatment is
      symptomatic, consisting of compounds that block enzymatic acetylcholine
      degradation (acetylcholinesterase inhibitors). Cognitive benefits of the four
      approved antidementia drugs are typically modest and limited in duration. While
      Alzheimer's disease is undoubtedly multifactorial in cause, advancing age is the
      most important risk factor. Any robust theory of pathogenesis must account for
      the profound influence of age on the emergence of Alzheimer's disease. There is
      evidence that senescent changes in cerebrospinal fluid production, circulation,
      turnover and clearance of amyloid beta-peptides may be a key factor in the onset
      and progression of Alzheimer's disease. The effect of increasing cerebrospinal
      fluid circulation and turnover in Alzheimer's disease patients by implanting a
      novel, low-flow drainage system (COGNIshunt) has been studied and promising
      trends in cognitive stabilization and improvement in cerebrospinal fluid
      biomarkers have been found.

PMID- 15853621
TI  - Assessment and prediction of functional impairment in vascular dementia.
AB  - Vascular dementia is associated with cognitive, physical and functional
      impairments that often lead to disability among the elderly. Declines in
      activities of daily living significantly contribute to the disability reported
      among patients with vascular dementia and compromise quality of life for both
      patients and their families. Assessment of activities of daily living is an
      important component of the diagnosis, tracking and management of vascular
      dementia patients. Furthermore, an understanding of the determinants of
      activities of daily living dysfunction may provide an earlier identification of
      individuals at risk for functional disability and allow opportunities for
      improved patient care. In this review, methods for assessing and tracking
      activities of daily living are discussed and the literature on the correlates of
      functional impairment in vascular dementia is summarized. Also, the potential use
      of executive dysfunction as a marker for instrumental activities of daily living
      impairment is discussed and recommendations for clinical practice and future
      research are provided.

PMID- 15853622
TI  - Nerve growth factor and chronic daily headache: a potential implication for
      therapy.
AB  - The pivotal role of nerve growth factor in inducing hyperalgesia and central
      sensitization has been emphasized in experimental pain models. Higher nerve
      growth factor levels have recently been found in the cerebrospinal fluid of
      patients with chronic daily headache. These levels were significantly correlated
      with the cerebrospinal fluid levels of substance P and calcitonin gene-related
      peptide, supporting the involvement of this neurotrophin in enhancing the
      production of the two sensory neuropeptides of the trigemino-vascular system in
      chronic daily headache. This may, in part, account for the long-lasting
      sensitization and activation of this system, which could contribute to headache
      chronicity. More recent research has shown a significant correlation between the
      higher cerebrospinal fluid levels of nerve growth factor and those of another
      neurotrophin, the brain-derived neurotrophic factor, as well as glutamate in
      chronic daily headache patients. These findings suggest the potential involvement
      of nerve growth factor-mediated upregulation of brain-derived neurotrophic factor
      in persistent head pain. Therefore, nerve growth factor appears to indirectly
      exert its effect through enhancing glutamatergic transmission involved in the
      processing of head pain via brain-derived neurotrophic factor. Based on these
      data, a potential application can be hypothesized for novel strategies targeting
      neurotrophins (nerve growth factor and brain-derived neurotrophic factor) and
      their receptors to chronic daily headache. To date, the majority of the molecules
      discovered in this regard have been scarcely or never proved in animal pain
      models and are far from clinical use in chronic pain, including chronic daily
      headache. If this approach is to be developed in the near future, research should
      be focused on identifying strategies with few central side effects and specific
      selective action on central sites involved in chronic head pain and more
      generally in chronic pain conditions. This will represent a very difficult
      challenge, taking into account the pleiotropic effect of nerve growth factor and
      the wide range of intracellular signalling pathways activated by this
      neurotrophin which are not limited to the nociceptive system.

PMID- 15853623
TI  - Therapy for neurocysticercosis.
AB  - Therapy for neurocysticercosis has advanced during the last 20 years with the
      advent of albendazole (Zentel) and praziquantel (Cysticide). Albendazole is the
      current medication of choice for the treatment of neurocysticercosis and is
      recommended for symptomatic patients with multiple viable cysts in the brain
      parenchyma. Albendazole may also be useful in extraparenchymal cysticercosis,
      especially in the subarachnoid racemose form, when complete surgical resection of
      the cysts is usually impracticable. Currently, there is an intense debate over
      the value and safety of anticysticercal therapy. Causes for failure of
      anticysticercal therapy include high inter-individual variability in plasma
      concentration of albendazole sulfoxide and the complex interactions of several
      drugs with the albendazole metabolite. Furthermore, albendazole sulfoxide is an
      enantiomeric mixture of (+)- and (-)-albendazole sulfoxide with accumulation of
      the (+)-enantiomer in the cerebrospinal fluid. However, the question over which
      enantiomer is effective against cysticerci remains to be clarified.

PMID- 15853624
TI  - Therapeutic drugs for targeting chloroquine resistance in malaria.
AB  - While the post-genomic era could lead into new targets for antimalarial drug
      development, herein few successful targets including medicinals involved in those
      processes are presented. Further, contribution of bioinorganic chemistry has also
      started to make its impact in the field of pharmaceuticals. Therefore, metal
      chelators, selected organometallics, and metalloantimalarials that would offer
      potential therapeutic drugs are also discussed. Finally, a brief summary on
      chloroquine-resistance mechanism(s) has been included.

PMID- 15853625
TI  - Folding and mis-folding of peptides and proteins: insights from molecular
      simulations.
AB  - In this paper, the main achievements and problems of the application of all-atom
      molecular simulations, with particular attention for Molecular Dynamics (MD),
      will be critically reviewed. Starting from unfolding simulations, through biased
      simulations, which require a knowledge of the native state conformation, to
      folding studies based on the simple knowledge of the protein (or peptide)
      sequence, the strengths and weaknesses of theoretical approaches to the study of
      folding and their matching with experimental observations will be discussed.
      Finally, we will give a critical outlook on the possible developments of this
      field in the near future.

PMID- 15853626
TI  - Therapeutics and prion disease: can immunisation or drugs be effective?
AB  - Prion diseases are of considerable importance because of the threat of a variant
      form of Creutzfeldt Jakob disease that has emerged in recent years. Pre-clinical
      diagnosis of prion diseases still remains poor and effective therapies also do
      not exist at present. This review examines research on possible therapeutic
      strategies that might have potential benefits if applied before neurodegeneration
      has occurred.

PMID- 15853627
TI  - Medicinal chemistry and properties of 1,2,4-thiadiazoles.
AB  - 1,2,4-Thiadiazole is a distinctive class of small heterocyclic thiol trapping
      agents that serve as an interesting pharmacophore in the design of inhibitors
      targeting the cysteine residues of proteins. X-Ray crystal structures of enzyme
      inhibitor complex indicate that the cysteine thiol reacts with the N-S bond of
      the thiadiazole moiety to form a disulfide bond resulting in the inactivation of
      the enzymes. This review addresses the medicinal chemistry and various properties
      of 1,2,4-thiadiazoles in their potential as new electrophilic "warheads" for
      targeting the cysteine residues of biomolecules (e.g, H+/K+ ATPase), and cysteine
      dependent enzymes (e.g., cathepsin B and transglutaminase).

PMID- 15853628
TI  - Endothelin receptor antagonists: an overview of their synthesis and structure
      activity relationship.
AB  - Endothelins (ETs) are potent vasoconstrictor peptides and are associated with
      several disease states like pulmonary hypertension, systemic hypertension and
      heart failure. Endothelin-1 (ET-1) is the first member of the family and it has
      the receptor subtypes known as ETA and ETB. The receptors ETA and ETB are
      attractive new therapeutic targets for diseases associated with elevated ET-1
      levels. Several studies have thus led to the discovery of selective ETA receptor
      antagonists as well as non-selective ETA/ETB antagonists. The preclinical and
      clinical studies have clearly established that these antagonists are effective in
      the treatment of essential hypertension, pulmonary hypertension, heart failure
      and atherosclerosis. The advances in this area have resulted in the FDA approval
      of the orally active dual antagonist Bosentan for pulmonary hypertension in 2001.
      This review highlights the synthesis and structure-activity of the endothelin
      receptor antagonists and covers the literature in this area up to 2001.

PMID- 15853629
TI  - Imidazole and benzimidazole derivatives as chemotherapeutic agents.
AB  - Imidazole and benzimidazole systems are presented in a large number of common
      therapeutics agents. They were widely used in organic and medicinal chemistry,
      but recently the development of N-oxide derivatives got an improvement from the
      point of view of its chemical and biological activity. Though we will review
      recent developments in chemical and biological profiles (as antitumoral,
      antiparasitic, antiviral and antimicrobial agents) of these heterocycle systems
      and the corresponding N-oxides.

PMID- 15853630
TI  - Cardiovascular toxicity from the perspective of oxidative stress, electron
      transfer, and prevention by antioxidants.
AB  - This review demonstrates that oxidative stress, reactive oxygen species, and
      electron transfer can serve as unifying mechanistic themes for large numbers of
      cardiovascular toxins, both endogenous and exogenous. Lipid peroxidation is a
      prevalent insult. Common among the various conditions are atherosclerosis and
      arrhythmia. The preventive effects of antioxidants are documented.

PMID- 15853631
TI  - Targeting small arteries of hypertensive status with novel ATP-sensitive
      potassium channel openers.
AB  - The excessive contraction of small arteries under high blood pressure is the main
      contributor to the pathological change of hypertension. Current anti-hypertensive
      drugs, which lack a selective effect on small arteries in a hypertensive state,
      may cause many adverse effects. We have developed a novel opener of ATP-sensitive
      potassium channels, iptakalim, the vasorelaxing action of which is determined by
      the hypertensive status of small arteries. In conscious stroke-prone,
      spontaneously hypertensive rats and "two-kidneys, one-clip" renal hypertensive
      dogs, this compound produced long-lasting hypotensive effects, with no tolerance.
      Furthermore, it exerted a protective effect against hypertensive damage to target
      organs. Given its potency and fewer side effects, iptakalim hydrochloride is a
      promising drug for the treatment of hypertension.

PMID- 15853632
TI  - Somatostatin: a hormone for the heart?
AB  - Somatostatin (somatotropin release inhibitory factor; SRIF) peptides are widely
      distributed throughout the mammalian body and act through a family of genetically
      distinct, guanine nucleotide regulatory protein coupled (G-protein-coupled), cell
      surface receptors (sst(1-5)). Compelling evidence shows that SRIF and SRIF
      peptidyl analogs modulate vascular function, with actions upon smooth muscle and
      endothelium. SRIF receptors are known to exist in the carotid endothelium, a
      principal target for the pro-inflammatory cascade that accompanies coronary
      artery disease. SRIF-14 and SRIF analogs are anti-inflammatory but the molecular
      mechanism involved remains unclear. Since crucial steps in the endothelial
      inflammation response include endothelial activation by cytokines, adhesion
      molecule expression and cell-monocyte interactions, peptide agents that inhibit
      these steps might provide a novel strategy for reducing vascular inflammation.
      SRIF, acting through its cognate receptors, modulates a variety of intracellular
      effectors that are linked to inflammation including phosphotyrosine phosphatases,
      the extracellular regulated protein kinase 1 and 2 (ERK1/2) cascade, adenylyl
      cyclase and endothelial nitric oxide synthase. Directly or indirectly, SRIF also
      functions to inhibit endothelial cell proliferation and induce apoptosis. A
      detailed understanding of SRIF actions could provide a rational basis for using
      SRIF ligands in controlling vascular inflammation and inhibiting cytokine
      signaling, critical events in atherogenesis.

PMID- 15853633
TI  - Is the vascular system a main target for thyroid hormones? From molecular and
      biochemical findings to clinical perspectives.
AB  - The cardiovascular system is an important target for thyroid hormones (THs).
      Until recently, our understanding of the biological role of THs has been largely
      based on a catalog of effects observed in excess or deficiency of THs. In the
      last decades, however, some important progress has been done in defining the
      molecular and biochemical basis of thyroid hormone action at the cellular and
      nuclear level. Most of the molecular and cellular mechanisms responsible for the
      effects of THs on the heart have been clarified, whereas few data are available
      about the mechanisms of action of THs on the vasculature. Data reported so far
      describe the thyroid hormone effects on the vascular system as indirect
      consequences of thermogenic or hemodynamic derangements. The aim of this review
      is to focus on the direct role of THs in the vascular system, to analyze the main
      factors involved in this regulatory process, to evaluate the causes of imbalance,
      their relationships to some pathophysiological conditions, and, finally, to
      hypothesize effective therapeutic approaches. Our review considers data on the
      molecular and biochemical properties of iodothyronine deiodinases, with
      particular attention to D2, the enzyme for the local conversion of the precursor
      thyroxine (T4) into the biologically active triiodothyronine (T3). We summarize
      data on the deiodinase tissue distribution, subcellular localization, topology
      and structure-activity relationships. We also discuss the physiological role of
      deiodinases and their involvement in the TH-mediated regulation of vascular
      function.

PMID- 15853634
TI  - Are the antioxidant properties of carvedilol important for the protection of
      cardiac mitochondria?
AB  - The cellular role of mitochondria includes ATP generation and the modulation of
      cytosolic calcium signals, besides being the "crossroads" for several cell death
      pathways. The maintenance of optimal mitochondrial functioning during the disease
      process increases the chances for survival. For example, ischaemia followed by
      reperfusion is known to negatively affect mitochondrial function, namely by
      inducing a deleterious condition called mitochondrial permeability transition
      (MPT). The MPT is responsible for mitochondrial dysfunction and can ultimately
      lead to cell death. Therefore, it seems important to protect mitochondrial
      function in cardiac disease. Carvedilol, a beta-adrenergic receptor antagonist
      with antioxidant properties, has a positive impact on cardiac mitochondria during
      in vitro, ex-vivo and in vivo models of cardiac dysfunction. Particularly,
      carvedilol was shown to inhibit MPT in isolated heart mitochondria and protect
      mitochondria against the oxidative damage induced by the xanthine
      oxidase/hypoxanthine pro-oxidant system. The observation that carvedilol acts as
      an inhibitor of mitochondrial complex-I is also of importance, since this
      mitochondrial system was proposed as cause of the cardiotoxicity associated with
      the anti-neoplasic drug doxorubicin. This review points out the major findings
      concerning the positive impact of carvedilol on mitochondrial function and its
      use in the treatment of myocardial diseases where oxidative stress is known to be
      involved.

PMID- 15853635
TI  - Urotensin II: a vascular mediator in health and disease.
AB  - Urotensin II is the most potent vasoconstrictor known. Paradoxically, urotensin
      II also possesses vasodilator activity in certain vascular beds. While much is
      still to be learnt regarding urotensin II's actions on vascular tone, it is now
      clear that it mediates its effects by interacting with a specific G-protein
      coupled receptor. The presence of urotensin II and its receptor in both
      vertebrate and invertebrate species suggests an evolutionarily conserved role in
      normal physiology although evidence is mounting for both species-specific as well
      as disease-specific effects of this peptide. This somatostatin-like peptide was
      originally thought to reside solely in compartments of the central nervous
      system. However, recent evidence implicated urotensin II in the pathogenesis of a
      variety of disease processes ranging from hypertension to hepatic cirrhosis.
      Increased expression of this peptide has been noted in cardiac, renal and hepatic
      disease. While the contribution of urotensin II to these diseases remains
      unclear, the advent of urotensin II antagonists allows for not only the
      possibility of a new range of therapeutic drugs but also new avenues of
      investigation and further mechanistic insights into the pathophysiology of these
      disease processes.

PMID- 15853636
TI  - The emerging roles of leptin and ghrelin in cardiovascular physiology and
      pathophysiology.
AB  - Leptin and ghrelin are novel peptide hormones which are counter-regulatory in the
      central control of appetite. More recently, it has become clear that these
      hormones have a range of effects on the cardiovascular system. Leptin increases
      sympathetic activity, producing a pressor effect when acting on the central
      nervous system. However, leptin produces vasodilation by an endothelium-dependent
      mechanism peripherally. Ghrelin decreases sympathetic activity and has a
      depressor effect when acting on the central nervous system. Peripherally, ghrelin
      produces vasodilation by an endothelium-independent mechanism. Ghrelin improves
      left ventricular function and cardiac cachexia in heart failure. Leptin may
      contribute to cardiac cachexia, and to obesity-related cardiomyopathy by a
      variety of mechanisms. Leptin has pro-inflammatory, proliferative and
      calcification promoting effects in the vasculature. Ghrelin has recently been
      shown to be anti-inflammatory in the vasculature. Leptin may also produce a pro
      thrombotic state through stimulation of platelet aggregation and inhibition of
      coagulation and fibrinolysis. The evidence for and against these effects as well
      as their pathophysiological significance in obesity hypertension, heart failure,
      atherosclerosis and thrombosis are discussed.

PMID- 15853637
TI  - Vascular calcifications in chronic kidney disease: are there new treatments?
AB  - Cardiovascular disease is extremely common in patients with end-stage renal
      disease (ESRD) and accounts for at least 50% of deaths among these patients.
      Vascular calcifications (VC) have been recently implicated as a possible cause of
      this excess cardiovascular mortality. Medial calcification is a striking feature
      of vascular disease in patients with ESRD. The traditional view that VC is a
      degenerative and passive process has been seriously challenged, based on strong
      evidence suggesting that VC is an active and highly regulated process similar to
      bone formation. Different data support the notion that elevated levels of
      phosphorus and/or other uremic toxins may play an important role by transforming
      vascular smooth muscle cells into osteoblast-like cells, which can produce bone
      matrix proteins. This nidus can then mineralize if the balance of pro
      mineralizing factors outweighs inhibitory factors. The advent of newer
      noninvasive screening tests have generated great interest for screening patients
      with ESRD for vascular calcifications. Control of serum phosphorus with
      sevelamer, a recently developed non-calcium, non-aluminum phosphate binder, have
      attenuated or arrested progression of coronary artery and aortic calcifications
      compared to treatment with calcium-based binders. Amino bisphosphonates, have
      shown to completely inhibit soft tissue calcifications, calciphylaxis and prevent
      death in animal models. The first generation bisphosphonate, etidronate, reduces
      the progression of coronary artery calcifications patients receiving long-term
      hemodialysis and intravenous pamidronate has produced a rapid improvement of
      calciphylaxis. In conclusion, VC is a widespread phenomenon in patients with ESRD
      with important cardiovascular consequences. A better understanding of the
      processes of VC is leading to therapies to retard or improve this phenomenon and
      will probably have an important impact on patient mortality.

PMID- 15853638
TI  - Obesity and cardiovascular physiology: impact of some pharmacological agents.
AB  - The increase in obesity prevalence is problematic as this condition is associated
      with health complications such as diabetes and cardiovascular diseases, more
      particularly when the excess body fat is stored in the deep abdominal region. The
      mainstay of therapy consists of behavior modification related to obesity such as
      overeating and physical inactivity. When these lifestyle modifying attempts fail,
      the use of anti-obesity drugs is warranted. Drug treatment is often indicated but
      is somewhat limited by the minimal number of well tolerated drugs that have
      proven to have long-term efficacy in maintaining body weight loss. The currently
      available drugs, sibutramine and orlistat, appear modestly effective in promoting
      weight loss. Ongoing studies continue to evaluate other drug treatments that may
      result in body weight reduction through a number of different mechanisms. Thus,
      the aim of this review is to present an overview of the current drugs available
      (particularly sibutramine and orlistat) as well as potential future candidates,
      and the impact of these agents on obesity and cardiovascular physiology.
      Furthermore, the therapeutic paradox of sibutramine in preventing obesity will be
      discussed as well as the beneficial impact of physical exercise on cardiac
      economy.

PMID- 15853639
TI  - Dihydropyridines, nitric oxide and vascular protection.
AB  - For more than decades calcium antagonists (CEBs) have been widely used for the
      treatment of myocardial ischaemia (angina pectoris). Among the classes of CEBs,
      the 1,4-dihidropyridine (DHPs) have been used for this indication because of
      their haemodynamic and electrophysiological properties. In particular, DHPs are
      compounds capable of vascular protection on both smooth muscle and endothelium.
      The main protective activity is related to their calcium antagonist activity. In
      addition, they present vascular dilatation function, which has been related to an
      anti-endothelin efficacy. The newer DHPs are endowed with slow onset and long
      duration of vasodilator activity and reduce coronary resistance with little or no
      effect on heart rate. The more lipophilic DHP, lacidipine, is also able to reduce
      the formation of atheroma plaque in animal models at therapeutic doses. It has
      potent and long-lasting antihypertensive properties and appears to protect the
      arterial wall against the development of atherosclerotic lesions in animal models
      or human subjects with severe and multiple risk factors. Additionally, it has
      been observed that: i) NO/cyclic GMP pathway facilitates the inhibitory effect of
      Ca(++) antagonists on KCl-evoked contraction in rat aorta; ii) Vasodilator effect
      of lacidipine was significantly attenuated in the presence of NO-synthase
      inhibitors; iii) DHPs stimulate an electrochemical activity related to the nitric
      oxide (NO) system within the aortic vessel tissue, in rats and mice. In
      particular, they implement endothelial NO at "useful" and not toxic nanomolar
      levels. These activities join the already described positive effects of these
      compounds upon vascular functions.

PMID- 15853641
TI  - The Akt/PKB family of protein kinases: a review of small molecule inhibitors and
      progress towards target validation.
AB  - This article describes recent advances in the development and biological
      evaluation of small molecule inhibitors for the serine/threonine kinase Akt
      (PKB). Akt plays a pivotal role in cell survival and proliferation through a
      number of downstream effectors. Recent studies indicate that unregulated
      activation of the PI3K/Akt pathway is a prominent feature of many human cancers
      and Akt is over-expressed or activated in all major cancers. Akt is considered an
      attractive target for chemotherapy and it has been postulated that inhibition of
      Akt alone or in combination with standard cancer chemotherapeutics will reduce
      the apoptotic threshold and preferentially kill cancer cells. The development of
      specific and potent inhibitors will allow this hypothesis to be tested in
      animals. The majority of small molecule inhibitors in this nascent field are
      classic ATP-competitive inhibitors which provide little specificity.
      Phosphatidylinositol (PI) analogs have been reported to inhibit Akt, but these
      inhibitors may also have specificity problems with respect to other PH domain
      containing proteins and may have poor bioavailability. None of the inhibitors in
      these classes have been reported to have Akt isozyme specificity. Recently, novel
      allosteric inhibitors have been reported which are pleckstrin homology domain
      dependent and exhibit Akt isozyme selectivity. Inhibitors in this class may have
      sufficient potency and specificity to test for tumor efficacy in animal models
      and recently reported preliminary experiments are reviewed.

PMID- 15853642
TI  - Mitotic kinesins: prospects for antimitotic drug discovery.
AB  - Kinesins, mechanochemical enzymes that utilize the energy of ATP to translocate
      along or destabilize microtubules, are essential for accurate completion of cell
      division. Recently, small moleculer inhibitors of one kinesin, kinesin spindle
      protein (KSP/Eg5/kinesin5), have been shown to be efficacious in pre-clinical
      studies, with one quinazolinone-based inhibitor advancing to Phase II clinical
      trials as a potential anticancer chemotherapeutic agent. This highlights the
      potential of KSP and other mitotic kinesins as targets for chemotherapeutic
      intervention. Ten other kinesins have been shown to play essential roles in cell
      division and thus may provide additional therapeutic opportunities. In this
      review, the biological roles of these proteins are described with emphasis on
      their importance to cell proliferation. In addition, kinesin motor domain
      structure and mechanism are described with particular attention given to the
      conformational changes that offer opportunities for chemical inhibition. Finally,
      a current list of KSP inhibitor classes is described in the context of their
      potential as clinical leads.

PMID- 15853643
TI  - The Hedgehog signaling pathway as a target for anticancer drug discovery.
AB  - The Hedgehog (Hh) signaling pathway directs the development of multiple tissues
      during embryonic development, and contributes to tissue homeostasis in adults.
      Deficient Hh signaling results in defective embryogenesis; conversely, excessive
      Hh signaling is associated with an inherited cancer predisposition syndrome
      (Gorlin Syndrome), and a growing list of sporadic human cancers. It is now clear
      that multiple components of "The Hh Pathway" can be altered in tumors. The Hhs
      are morphogens that signal through effectors that are largely unprecedented in
      drug discovery, with many key concepts derived from studies in Drosophila
      melanogaster. However, studies in tumor cell lines have recently identified
      targets that can be exploited for the discovery of human Hh antagonists, with
      additional targets likely to emerge as the human pathway is further defined.
      Here, we review basic aspects of Hh signal transduction, with an emphasis on
      molecular targets for drug discovery. The use of first-generation Hh antagonists
      such as cyclopamine will also be discussed; such agents remain invaluable in
      ongoing efforts to validate drug discovery assays and survey tumor lines for Hh
      dependence. The various types and frequencies of Hh signaling defects in
      different human tumors will also be reviewed, as will the status of medicinal
      chemistry efforts to discover novel Hh antagonists. In section VI, we review
      assays from the literature that could be utilized to discover new Hh antagonists
      for the treatment of cancer.

PMID- 15853644
TI  - Small molecule inhibitors of p53/MDM2 interaction.
AB  - The discovery of the key negative regulator MDM2 (mouse double minute 2, also
      termed HDM2 for its human equivalent) provided a great opportunity to manipulate
      the levels of the tumor suppressor p53 in cancer cells. Activation of p53 in
      tumor cells by inhibiting the interaction of MDM2 with p53 has therefore been the
      focus of a large effort in drug discovery. The modulation of protein-protein
      interactions, however, has historically been very difficult to achieve owing to
      the large surface area of interaction. In this article, we review the recent
      accomplishments in this area and our quest for a clinically viable MDM2
      inhibitor.

PMID- 15853645
TI  - Recent advances in the development of selective small molecule inhibitors for
      cyclin-dependent kinases.
AB  - Loss of normal cell cycle regulation is the hallmark of human cancers, and
      alteration of the components involved in cell cycle regulation occurs in most
      human tumors. This suggests that Cyclin dependent kinases (CDKs) are an
      attractive target for the development of pharmacological agents for the treatment
      of cancer. Recently, CDK family members that are not directly involved in cell
      cycle regulation have been identified. This includes CDK7, CDK8, and CDK9, which
      participate in transcription regulation, and CDK5, which plays a role in neuronal
      and secretory functions. Given the involvement of CDKs in multiple cellular
      processes, development of selective small molecule inhibitors for specific CDKs
      is expected to help clarify whether improved specificity of cell cycle CDK
      inhibitors will enhance their therapeutic potential in cancer treatment.
      Selective inhibitors are also needed as tools to explore the biology of diseases
      in which CDKs may participate and to help develop therapeutics to treat them.
      Intensive screening and drug design based on CDK/inhibitor co-crystal structure
      and SAR studies have led to the identification of a large variety of chemical
      inhibitors of CDKs. Although they are competitive with ATP at the catalytic site,
      their kinase selectivity varies greatly, and inhibitors selective for certain
      CDKs have begun to be identified. There are currently two categories of selective
      CDK inhibitors: those that are selective for CDK2 and CDK1 and those that are
      selective for CDK4/6. These two types of inhibitors have different effects on
      tumor cells and are expected to be useful in the treatment of cancer.

PMID- 15853646
TI  - Progress in the discovery of polo-like kinase inhibitors.
AB  - Polo-like kinases (PLKs) are key enzymes that control mitotic entry of
      proliferating cells and regulate many aspects of mitosis necessary for successful
      cytokinesis. Of the four known human PLKs, PLK1 is the best characterized and is
      overexpressed in many tumour types with aberrant elevation frequently
      constituting a prognostic indicator of poor disease outcome. Despite the fact
      that PLK1 has been regarded as a validated mitotic cancer target for a number of
      years, very few reports of small-molecule PLK inhibitors have appeared to date.
      In order to provide a starting point for the discovery and development of
      selective PLK inhibitors, we have characterized a number of known generic kinase
      inhibitors with hitherto unknown activity against PLK1, as well as discovering
      novel inhibitors through structure-guided design. Previously, the only
      characterized biochemical PLK1 inhibitor was scytonemin, a symmetric indolic
      marine natural product that is a micromolar non-specific ATP competitor. In
      addition to the progress in the development of ATP-competitive small-molecule PLK
      inhibitors, recent reports on the use of antisense oligonucleotides (ASONs) and
      small interfering RNAs (siRNAs) directed against PLK1 have shown selective
      antiproliferative effects on cancer cells both in vitro and in vivo, producing
      phenotypes consistent with known PLK functions, and confirming that targeting
      PLKs with conventional small-molecule agents may be a valid and effective
      anticancer strategy. Here we present a progress update on the approaches taken so
      far in developing PLK inhibitors.

PMID- 15853647
TI  - Progress in the development of selective inhibitors of Aurora kinases.
AB  - Errors in the mitotic process are thought to be one of the principal sources of
      the genetic instability that hallmarks cancer. Unsurprisingly, many of the
      proteins that regulate mitosis are aberrantly expressed in tumour cells when
      compared to their normal counterparts. These may represent a good source of
      targets for the development of novel anti-cancer agents. The Aurora kinases
      represent one such family of mitotic regulators. In recent years there has been
      intense interest in both understanding the role of the Aurora kinases in cell
      cycle regulation and also in developing small molecule inhibitors as potential
      novel anti-cancer drugs. With several companies now starting to take Aurora
      kinase inhibitors into clinical development, the time is right to review the
      medicinal chemistry contribution to developing the field, in particular to review
      the increasingly broad range of small molecule inhibitors with activity against
      this kinase family.

PMID- 15853648
TI  - Progress towards therapeutic small molecule MEK inhibitors for use in cancer
      therapy.
AB  - This paper reviews recent progress in the design and evaluation of MEK inhibitors
      as cancer therapeutics. Activation of the Ras / Raf / MEK / MAP kinase pathway
      has been implicated in uncontrolled cell proliferation and tumor growth. Mutated,
      oncogenic forms of Ras are found in 50% of colon, 90% of pancreatic and 30% of
      lung cancers. Recently, B-Raf mutations have been identified in more than 60% of
      malignant melanomas and from 40-70% of papillary thyroid cancers. MEK, a dual
      specificity kinase, is a key player in this pathway; it is downstream of both Ras
      and Raf and activates ERK1/2 through phosphorylation of key tyrosine and
      threonine residues. Representative examples of both ATP competitive and non
      competitive inhibitors as well as natural product based inhibitors will be
      discussed.

PMID- 15853649
TI  - Structural organization of the regulatory domain of human 5-lipoxygenase.
AB  - The enzyme 5-lipoxygenase (5-LO) initiates the synthesis of leukotrienes. For
      this reason, 5-LO activity is important for immune defense, whereas improper
      regulation contributes to pathogenesis, including chronic inflammation, asthma
      and atherosclerosis. Like all lipoxygenases, the 5-LO protein consists of two
      domains, a regulatory domain and a catalytic domain. Naturally, the regulatory
      domain determines catalytic activity and controls leukotriene synthesis. This
      domain shares features with classical C2 domains in that it has a beta-sandwich
      structure and binds calcium, nucleotides and phospholipids. However, important
      structural features place this domain in a distinct family, the PLATs (for
      Polycystin-1, Lipoxygenase, alpha-Toxin). In this review, we summarize our
      current understanding of the three dimensional organization of this important
      component of the 5-LO molecule. In addition, we point to findings from structural
      analyses of related proteins to suggest further details relating 5-LO structure
      to function.

PMID- 15853650
TI  - Molecular recognition of cyclic-nucleotides and current sensors for their
      detection.
AB  - This work briefly describes available sensors for cAMP and cGMP. Many sensors are
      based on derivatization of naturally occurring products such as immunoglobulins,
      protein kinases, etc. Only a few published works deal with chemosensors, which
      are built up by "total" chemical synthesis. This field stays opened for
      combinatorial chemist. The best sensors are protein kinases genetically modified
      with mutants of green fluorescent protein, which allow screening of entire cell
      cultures.

PMID- 15853651
TI  - SH3-like fold proteins are structurally conserved and functionally divergent.
AB  - The folding space for all the protein sequences is limited. Therefore it was
      observed that many proteins, whose sequences are not related, have similar fold
      characteristics. The fold databases like SCOP and CATH have classified various
      protein folds. However, in-depth analysis of the functional features of these
      folds was not done. We analyzed about twenty unique SH3-like folded proteins in
      their structural environment and functional characteristics. From our analysis it
      is apparent that the SH3-like folds could carry out various functions by
      modulation of loops and the functional region is restricted to one side of a
      particular sheet helped by two or three loops. The functions vary from
      oligonucleotide-binding to peptide-binding and other ligand binding. Although
      certain degree of sequence similarity was observed among the SH3-fold proteins,
      the similarity was restricted to the beta-strand regions of the proteins.

PMID- 15853652
TI  - Design and structure of peptide and peptidomimetic antagonists of protein-protein
      interaction.
AB  - Peptides based on the amino acid sequences found at protein-protein interaction
      sites make excellent leads for antagonist development. A statistical picture of
      amino acids involved in protein-protein interactions indicates that proteins
      recognize and interact with one another through the restricted set of specialized
      interface amino acid residues, Pro, Ile, Tyr, Trp, Asp and Arg. These amino acids
      represent residues from each of the three classes of amino acids, hydrophobic,
      aromatic and charged, with one anionic and one cationic residue at neutral pH.
      The use of peptides as drug leads has been successfully used to search for
      antagonists of cell-surface receptors. Peptide, peptidomimetic, and non-peptide
      organic inhibitors of a class of cell surface receptors, the integrins, currently
      serve as therapeutic and diagnostic imaging agents. In this review, we discuss
      the structural features of protein-protein interactions as well as the design of
      peptides, peptidomimetics, and small organic molecules for the inhibition of
      protein-protein interactions. Information gained from studying inhibitors of
      integrin functions is now being applied to the design and testing of inhibitors
      of other protein-protein interactions. Most drug development progress in the past
      several decades has been made using the enzyme binding-pocket model of drug
      targets. Small molecules are designed to fit into the substrate-binding pockets
      of proteins based on a lock-and-key, induced-fit, or conformational ensemble
      model of the protein binding site. Traditionally, enzymes have been used as
      therapeutic drug targets because it was easier to develop rapid, sensitive
      screening assays, and to find low molecular weight inhibitors that blocked the
      active site. However, for proteins which interact with other proteins, rather
      than with small substrate molecules, the lack of binding pockets means that this
      approach will not generally succeed. There exist many diseases in which the
      inhibition of protein-protein interactions would provide therapeutic benefit, but
      there are no general methods available to address such problems. The focus of the
      first part of this review is to discuss the features of protein-protein
      interactions which may serve as general guidelines for the development and design
      of inhibitors for protein-protein interactions. In the second part we focus on
      the design of peptides (lead compounds) and their conversion into peptidomimetics
      or small organic molecules for the inhibition of protein-protein interactions. We
      draw examples from the important and emerging area of integrin-based cell
      adhesion and show how the principles of protein-protein interactions are followed
      in the discovery, optimization and usage of specific protein interface peptides
      as drug leads.

PMID- 15853653
TI  - From structure to function: methods and applications.
AB  - The rapid increase in experimental data along with recent progress in
      computational methods has brought modern biology a step closer toward solving one
      of the most challenging problems: prediction of protein function. Comprehension
      of protein function at its most basic level requires understanding of molecular
      interactions. Currently, it is becoming universally accepted that the scale of
      the accumulated data for analysis and for prediction necessitate highly efficient
      computational tools with appropriate application capabilities. The review
      presents the up-to-date advances in computational methods for structural pattern
      discovery and for prediction of molecular associations. We focus on their
      applications toward a range of biological problems and highlight the advantages
      of the combination of these methods and their integration with biological
      experiments. We provide examples, synergistically merging structural modeling,
      rigid and flexible structural alignment and detection of conserved structural
      patterns and docking (rigid and flexible with hinge-bending movements). We hope
      the review will lead to a broader utilization of computational methods, and their
      cross-fertilization with experiment.

PMID- 15853654
TI  - Immunomodulatory peptides from IgSF proteins: a review.
AB  - The immunoglobulin (Ig) domain is a highly conserved domain predominantly
      observed in cell surface proteins due to its ability to resist proteolysis. By
      mutation and selection the Ig domain has evolved to serve diverse biological
      functions including growth and development, signaling, adhesion and protein
      carbohydrate interactions. Collectively, proteins with Ig-like domain constitute
      the immunoglobulin superfamily (IgSF). The IgSF proteins make up over 2% of human
      genes constituting the largest gene family in the human genome. Analogous to the
      complementarity determining regions (CDR)s that form the antigen combining sites
      of the antibody, the high specificity of the IgSF receptor-ligand interaction is
      attributed to the sequence and structure of the CDR-like regions unique to each
      IgSF protein. Hence, CDR-like regions provide ideal templates for the design of
      mimetics that can potentially perturb specific IgSF receptor/ligand interactions.
      The determinants of binding are localized near the CDR-like regions, conformation
      is determined locally and is unique for each loop. In structure based drug design
      one of the approaches to identify lead agents is to map the receptor/ligand
      binding epitope onto a small peptide. Data from theoretical, structural and
      functional studies have been adopted in the design of novel peptide antagonists
      of the IgSF protein-protein interactions. Many peptide antagonists have shown
      significant therapeutic potential in multiple animal models. The design of the
      IgSF peptide analogs, rationale as therapeutic targets, functional efficacy and
      the clinical benefits are reviewed here.

PMID- 15853655
TI  - Chaperone activities of the 26S and 20S proteasome.
AB  - The accumulation of misfolded or damaged proteins causes the failure of normal
      cell structure and functions necessary for growth and viability. To abort this
      adverse development, defective proteins must be rapidly repaired by molecular
      chaperones or destroyed by energy-dependent cytoplasmic proteases. A balance
      among these processes ultimately maintains cellular homeostasis. In eukaryotes,
      the 26S proteasome, a protease/chaperone complex, is a central component in the
      protein triage decision process. The 26S proteasome generally acts as a
      ubiquitination system, though it also selectively degrades structurally abnormal
      proteins in an ubiquitin-independent manner. In either case, all substrate
      proteins must undergo structural changes and stabilization necessary for their
      rapid degradation. It has, therefore, often been suggested that several chaperone
      functions are closely related to the stimulation of proteasomal degradation. This
      review summarizes recent discoveries pertaining to chaperone activities in the
      proteasomal degradation pathway, and to their regulation of protein breakdown
      mediated by the proteasome.

PMID- 15853657
TI  - Lipid nucleoside conjugates for the treatment of cancer.
AB  - Phospholipid nucleoside conjugates and nucleosides with chemical additions to the
      hydroxyl and amino moieties have been used since the 1970s in order to increase
      the biological activity of the parent compound. Previous investigators have found
      that adding lipid moieties to ara-C or chemically linking ara-C to a phospholipid
      creates a prodrug that exhibits superior cytotoxic activity compared to ara-C
      alone when used in animal tumor models. The novel ara-C molecules reveal
      different pharmacological profiles from the parent compound such as decreased
      catabolism by cytidine deaminase, increased plasma half-life, and release of
      nucleoside monophosphate, a reaction that bypasses the rate limiting initial
      nucleoside phosphorylation. Additionally, these compounds were able to penetrate
      the blood-brain barrier and were active against tumor cells implanted i.c. The
      purpose of this review is to briefly cover the history and successes of previous
      investigators who have synthesized and tested these phospholipid ara-C
      conjugates, to discuss recent phospholipid ara-C and fludarabine conjugates, and
      to discuss the synthetic design and synthesis of a novel phospholipid gemcitabine
      conjugate. These phospholipid nucleoside conjugates possess the potential to have
      superior anti-neoplastic cytotoxicity profiles with fewer side effects than the
      parent nucleoside and merit further investigation.

PMID- 15853658
TI  - A mechanistic approach to anticancer therapy: targeting the cell cycle with
      histone deacetylase inhibitors.
AB  - The activity of genes encoded by the highly-condensed DNA in cellular nuclei must
      be precisely regulated. Regulation of the accessibility of gene promoters to
      transcription complexes is one level of gene regulation and is influenced by
      histone tail modifications such as acetylation, methylation, and phosphorylation.
      Acetylation is a reversible modification catalyzed by histone acetyl transferase
      (HAT) and histone deacetyltransferase (HDAC) enzymes. Histone deacetylation is
      associated with transcriptional repression of genes, as the removal of acetyl
      groups from lysine residues allows for tighter electrostatic interactions between
      DNA and histones, limiting accessibility of the DNA for transcription. Inhibition
      of HDAC activity permits histones to remain in an acetylated state, and through
      the resulting alterations in gene regulation, inhibits cell cycle progression,
      inhibits differentiation, and in some cases induces apoptosis. Inhibition of
      proliferation by HDAC inhibitors is characterized by arrest at the G1 or G2/M
      phases of the cell cycle. Many types of tumor cells then undergo programmed cell
      death. Exposure to HDAC inhibitors may also allow reactivation of tumor
      suppressor genes which had been silenced by hypoacetylation during tumorigenesis.
      HDAC inhibitors from a number of chemical classes have shown promise as anti
      cancer agents in animal studies and early clinical trials. The development of
      HDAC inhibitors which specifically target HDAC isozymes, and more detailed
      understanding of their anti-neoplastic actions, heralds a new epigenetic
      antitumor therapeutic strategy.

PMID- 15853659
TI  - Targeting telomerase by antisense-based approaches: perspectives for new anti
      cancer therapies.
AB  - Oligonucleotide-based therapies have been under investigation for many years, and
      different antisense oligomers are being tested in clinical trials on patients
      with cancer and other diseases. Since telomerase reactivation has been defined as
      one of the six hallmarks of cancer because of the enzyme's ability to provide
      tumor cells with unlimited proliferative potential, antisense-based approaches,
      aimed to inhibit the core enzyme components, could represent innovative
      anticancer therapies. Overall, available information indicates antisense-based
      strategies as powerful tools to inhibit telomerase and interfere with tumor cell
      proliferative potential. Specifically, cancer cell growth arrest was observed in
      several tumor models as a consequence of telomere shortening in the presence of
      prolonged telomerase inhibition. However, in other studies, antisense-based
      treatments caused rapid loss of tumor cell viability and induced apoptosis
      independently of telomere attrition. The results would suggest that telomerase
      inhibition affects tumor cell growth by mechanisms that are dependent as well as
      independent of the enzyme telomere elongating activity. However, the role of
      telomerase in tumorigenesis and tumor progression, beyond the classical mechanism
      of telomere lengthening, needs to be further investigated to provide a better
      rationale for the design and development of antitelomerase-based therapies in
      clinical oncology.

PMID- 15853660
TI  - Novel insights into c-Src.
AB  - Since identifying a transmissible agent responsible for tumorigenesis in
      chickens, the v-Src oncogene, significant progress has been made in determining
      the functions of its cellular homologue. c-Src is the product of the SRC gene and
      has been found both over-expressed and highly activated in a number of human
      cancers. In fact the relationship between c-Src activation and cancer progression
      is significant. Furthermore c-Src may play a role in the acquisition of the
      invasive and metastatic phenotype. In this review we will summarize some of the
      latest evidence for the role of c-Src in tumorigenesis and particularly in human
      tumor progression. In this review, specifically, we will address growth signals,
      adhesion, migration, invasion, angiogenesis and functional genomics.

PMID- 15853661
TI  - Hsp90 inhibitor geldanamycin and its derivatives as novel cancer chemotherapeutic
      agents.
AB  - Geldanamycin, an ansamycin-derivative benzoquinone compound, was originally
      isolated as a natural product with anti-fungal activity. Later, geldanamycin was
      found to have anti-proliferative activity on tumor cells transformed by oncogene
      kinases such as v-Src. Geldanamycin neither bind nor inhibit oncogene kinases
      directly, but specifically binds and inhibits a major molecular chaperone, Hsp90.
      Hsp90 is a highly abundant and essential cytosolic protein and the expression
      level of Hsp90 increases by environmental stress. Hsp90 functions as a molecular
      chaperone by binding to various cellular proteins and supporting the proper
      folding, stability, and function of target proteins. The Hsp90 client proteins
      include a wide variety of signal-transducing proteins that regulate cell growth
      and differentiation, such as protein kinases and steroid hormone receptors. Hsp90
      functions in an ATP-dependent manner in cooperation with other molecular
      chaperones such as Cdc37 and FKBP52. Geldanamycin specifically inhibits the
      essential ATPase activity of Hsp90. Thus, treatment of cells with geldanamycin
      results in inactivation, destabilization, and degradation of Hsp90 client
      proteins. Because Hsp90 client proteins play important roles in the regulation of
      the cell cycle, cell growth, cell survival, apoptosis, and oncogenesis,
      geldanamycin obstructs the proliferation of cancer cells and shows anti-cancer
      activity in experimental animals. Although difficulties with solubility and
      toxicity should be overcome, Hsp90 inhibitors will be potential and effective
      cancer chemotherapeutic drugs with a unique profile. In fact, a modified
      geldanamycin with lower toxicity, 17-allylaminogeldanamycin (17-AAG), has been
      examined in phase I clinical trials with encouraging results.

PMID- 15853662
TI  - Receptor tyrosine kinases and anticancer therapy.
AB  - Receptor and non-receptor protein tyrosine kinases (PTKs) are essential enzymes
      in cellular signaling processes and signal transduction pathways that regulate
      cell growth, differentiation, migration and metabolism by catalyzing protein
      phosphorylation and dephosphorylation. In recent years, different tyrosine kinase
      receptors were identified as regulators of tumor or tumor vessel growth. Their
      inhibition by specific tyrosine kinase inhibitors and antibodies targeting growth
      factors and their receptors were recently shown to constitute a new modality for
      treating cancers. The pathognomonic role of the inhibited tyrosine kinase defines
      the way of action, whereas the amount of expression in tumor tissue is thought to
      define the indication for the tumor entity. Various compounds targeting PTKs are
      under clinical investigation in phase I-III trials or are already approved. This
      review describes new drugs targeting BCR-Abl, c-kit, EGFR (epidermal growth
      factor receptor), tumor angiogenesis via VEGF (vascular endothelial growth
      factor), HER2/neu and "multitarget" tyrosine kinase inhibitors.

PMID- 15853663
TI  - Apoptosis following photodynamic tumor therapy: induction, mechanisms and
      detection.
AB  - As a treatment modality for malign and certain non-malignant diseases,
      photodynamic therapy (PDT) involves a two step protocol which consists of the
      (selective) uptake and accumulation of a photosensitizing agent in target cells
      and the subsequent irradiation with light in the visible range. Reactive oxygen
      species (ROS) produced during this process cause cellular damage and, depending
      on the treatment dose/severity of damage, lead to either cellular
      repair/survival, apoptotic cell death or necrosis. PDT-induced apoptosis has been
      focused on during the last years due to the intimate connection between ROS
      generation, mitochondria and apoptosis; by this PDT employs mechanisms different
      to those in the action of radio- and chemotherapeutics, giving rise to the chance
      of apoptosis induction by PDT even in cells resistant to conventional treatments.
      In this review, the (experimental) variables determining the cellular response
      after PDT and the known mechanistic details of PDT-triggered induction and
      execution of apoptosis are discussed. This is accompanied by a critical
      evaluation of wide-spread methods employed in apoptosis detection with special
      respect to in vitro/cell-based methodology.

PMID- 15853664
TI  - Targeting cytotoxic conjugates of somatostatin, luteinizing hormone-releasing
      hormone and bombesin to cancers expressing their receptors: a "smarter"
      chemotherapy.
AB  - Chemotherapy is one of the main modalities in the therapy of cancer. However, an
      improvement in the efficacy and a reduction in the toxicity of chemotherapeutic
      agents remains a great challenge to oncologists. A specific delivery of cytotoxic
      drugs to cancerous cells may help improving both aspects. Peptide hormones, for
      which receptors have been found in various human cancers, can serve as carriers
      for a local delivery of cytotoxic agents or radiopharmaceuticals to the tumors,
      as demonstrated by the successful clinical use of radiolabeled somatostatin
      analog Octreoscan for the detection and treatment of some somatostatin receptor
      positive tumors. Thus, in recent years we developed a series of cytotoxic peptide
      hormone conjugates based on derivatives of hypothalamic hormones such as
      somatostatin and luteinizing hormone-releasing hormone (LHRH), and the brain-gut
      hormone bombesin. To create targeted conjugates with high cytotoxic activity, a
      derivative of doxorubicin (DOX), 2-pyrrolino-DOX (AN-201), which is 500-1, 000
      times more active than its parent compound, was developed. This agent was coupled
      to somatostatin octapeptide RC-121 to form cytotoxic conjugate AN-238, and to [D
      Lys6]LHRH carrier to produce analog AN-207. Cytotoxic bombesin hybrid AN-215 also
      contains AN-201. DOX was likewise linked to [D-Lys6]LHRH to form AN-152. A
      comprehensive testing of these cytotoxic conjugates in experimental models of
      various human and rodent cancers led to their selection as candidates for
      clinical trials.

PMID- 15853665
TI  - Autologous formalin-fixed tumor vaccine.
AB  - A novel tumor vaccine consisting of autologous formalin-fixed tumor fragments,
      cytokine-encapsulated microparticles, and an adjuvant was developed. Although
      mice experiments revealed mild efficacy, vaccination in a Phase I/IIa clinical
      trial of patients after resection of hepatocellular carcinoma resulted in
      significantly longer time before the first recurrence with no problematic adverse
      effect, than compared to historical control patients operated in the same
      department. In the followed academic Phase IIb randomized clinical trial, the
      vaccination significantly improved the recurrence-free survival and overall
      survival rates in a median follow-up of 15 months. The vaccine will be promising
      against recurrence of many types of human cancers after resection.

PMID- 15853666
TI  - New methodologies for ligand-based virtual screening.
AB  - Computational screening of compound databases has become increasingly popular in
      pharmaceutical research. Virtual screening approaches can roughly be divided into
      target structure-based screening (often referred to as docking) and screening
      using active compounds as templates (ligand-based virtual screening). Ligand
      based screening techniques essentially focus on comparative molecular similarity
      analysis of compounds with known and unknown activity, regardless of the methods
      or algorithms used. In this review, we first provide an overview of widely used
      ligand-based virtual screening approaches including various database filters and
      then discuss recent trends in this field and new methodological developments.

PMID- 15853667
TI  - Cell therapy for inner ear diseases.
AB  - Degeneration of inner ear cells, especially sensory hair cells and associated
      neurons, results in hearing impairment and balance disorders. These disabilities
      are incurable because loss of hair cells and associated neurons is currently
      irreversible. Protection or regeneration of hair cells and associated neurons is
      an important area of research for developing an effective treatment for inner ear
      diseases. Cell therapy is a rapidly growing area of research and has potential
      applications in the treatment of inner ear disorders. The first attempts to
      examine the feasibility of cell therapy in the treatment of inner ear disorders
      have been performed using neural stem cells (NSCs). Grafted NSCs can survive in
      the inner ear and differentiate into neural, glial and/or hair cell-phenotypes,
      making NSC transplantation for the restoration of inner ear cells a potentially
      viable treatment. Further studies have suggested embryonic stem cells (ESCs),
      dorsal ganglion cells and cell lines derived from fetal inner ear cells could be
      used to restore damaged inner ear cells. Cell transplantation has also been
      suggested as a strategy for drug delivery into the inner ear, and the ability of
      NSC-derived cells to produce neurotrophins in the inner ear has been
      demonstrated. Results from studies using autologous bone marrow stromal cells
      (MSCs) indicate a high survival and migration potential suggesting that MSCs can
      be used as a drug delivery vehicle to the inner ear. These cell transplantation
      findings provide a sound foundation for the development of therapies to treat
      inner ear disorders.

PMID- 15853669
TI  - Pathophysiology of blood-spinal cord barrier in traumatic injury and repair.
AB  - Blood-spinal cord barrier (BSCB) plays an important role in the regulation of the
      fluid microenvironment of the spinal cord. Trauma to the spinal cord impairs the
      BSCB permeability to proteins leading to vasogenic edema formation. Several
      endogenous neurochemical mediators and growth factors contribute to trauma
      induced BSCB disruption. Studies carried out in our laboratory suggest that those
      drugs and neurotrophic factors capable to attenuate the BSCB dysfunction
      following trauma are neuroprotective in nature. Whereas, agents that do not exert
      any influence on the BSCB disruption failed to reduce cell injury. These
      observations are in line with the idea that BSCB disruption plays an important
      role in the pathophysiology of spinal cord injuries. The probable mechanism(s) of
      trauma induced BSCB dysfunction and its contribution to cell injuries are
      discussed.

PMID- 15853670
TI  - TNF(alpha) modulation of visceral and spinal sensory processing.
AB  - The cytokine tumor necrosis factor(alpha) (TNF(alpha)) is associated with a
      constellation of physiological and behavioral characteristics that follow in
      response to infection such as fever, fatigue, listlessness, loss of appetite,
      malaise, and tactile hypersensitivity. These responses are examples of central
      nervous system (CNS) functions modified by the activated immune system. Our
      studies have focused on the involvement of TNF(alpha) in CNS control of
      gastrointestinal function and "visceral malaise". We have demonstrated that
      TNF(alpha) can elicit gastric stasis in a dose-dependent fashion via its
      interaction with vago-vagal neurocircuitry in the brainstem. Sensory elements of
      the vago-vagal reflex circuit (i.e., neurons of the solitary tract [NST] and area
      postrema [AP]) are activated by exposure to TNF(alpha), while the efferent
      elements (i.e., dorsal motor neurons of the vagus [DMN]) cause gastroinhibition.
      Transient exposure to low doses of TNF(alpha) cause potentiated (exaggerated) NST
      responses to stimulation. Subsequent studies suggest that TNF(alpha)
      presynaptically modulates the release of glutamate from primary afferents to the
      NST. Using immunohistochemical studies, we have observed the constitutive
      expression of the TNFR1 receptor on central vagal afferents and spinal trigeminal
      afferents in the medulla, as well as on cells and afferent fibers within the
      dorsal root ganglia and within laminae I and II of the dorsal horn throughout the
      spinal cord. The constitutive presence of these receptors on these afferents may
      explain why inflammatory or infectious processes that generate TNF(alpha) can
      disrupt gastrointestinal functions and cause tactile hypersensitivity. These
      receptors may also play a critical role in the chronic allodynia and hyper
      reflexia observed after spinal cord injury or peripheral nerve damage.

PMID- 15853671
TI  - From discovery to clinical trials: treatment strategies for central neuropathic
      pain after spinal cord injury.
AB  - Spinal cord injuries (SCI) result in a devastating loss of function below the
      level of the lesion in which there are variable motor recoveries and, in the
      majority of cases, central neuropathic pain syndromes (CNP) develop several
      months to years following injury. Unfortunately, the study of chronic pain after
      SCI has been neglected in the past due in part to the lack of good animal models
      but largely due to the clinically held dogma that CNP is not a real phenomenon
      and is psychogenic in nature rather than based on described pathophysiological
      mechanisms. The purpose of this article is to offer standardized terminology of
      pain, insight into animal modeling issues of CNP, descriptions of current
      clinical therapies and to discuss the pathophysiological mechanisms that provide
      the substrate for CNP that will lead to innovative new therapies. It is hoped
      that this information will give insight for research strategies as well as better
      care not only of SCI individuals, but is generalizable to many other CNP
      syndromes.

PMID- 15853672
TI  - Research on the possibility of overcoming traumatic paraplegia and its first
      clinical results.
AB  - The interruption of the continuity of the spinal cord is still an incurable
      lesion. In contrast with the peripheral nerves, the axons regenerating from the
      mother cells of the brain do not progress inside the cord. The reasons of this
      "non-permissiveness" are still unclear. This article describes the attempts of
      the author to overcome this non-permissiveness by means of a research that began
      in 1980 on rats, and continued since 1993 on monkeys. Results of the research on
      experimental animals were good and convincing so that this operation has been
      performed on fully informed human being volunteers affected by total severance of
      the cord between T8 and T11. Results of the first clinical cases are presented
      regarding operations performed either by rerouting the ulnar nerve to the lower
      limbs, or connecting the rostral stump of the severed cord with peripheral nerves
      of the hip to obtain rudimentary, but efficient, walking. Recovery occurred well
      in advance of the expected time, and continued to improve up to allow the first
      patient operated on by connecting CNS with PNS to walk with sticks after having
      walked for some months with a walker. This connection functioned even if the
      axons activating the single muscles were from mother cells dispersed in different
      regions of the brain cortex. These cells fire together giving selective
      contraction of diverse muscles. Furthermore, function occurred although the upper
      motor neuron uses the neurotransmitter glutamate, whereas motor end plates use
      receptors for acetylcholine. These data are under further investigation to
      determine whether the upper motor neuron changes the transmitter, or if the motor
      end changes its receptors (as seems to be by the first results).

PMID- 15853673
TI  - Motor control in the human spinal cord and the repair of cord function.
AB  - In this review we describe clinical and neurophysiological features of motor
      control in human spinal cord injury based on two models. First, motor control is
      considered in subjects with injury-induced complete division of the spinal cord
      from brain and brainstem structures, and second, in those in which the division
      is partial. We describe motor control in terms of segmental and plurisegmental
      reflex activity that dominates motor unit output to the muscles following
      complete separation from the brain motor structures by accidental injury. With
      incomplete separation of the spinal cord from brain structures, motor control is
      defined as the voluntary manipulation of reflex and automatic activity integrated
      with internal and external feedback signals. We review here motor control found
      after complete spinal cord injury with paradigm of single and regular-repeating
      stimuli applied to elicit cutaneous and muscle stretch reflex responses. We
      argue, that isolated spinal cord neural circuitry is capable of organizing
      characteristic reflex events that depend on the characteristics of the stimulus.
      Also, the profile of residual brain and brainstem, modified by the reduction in
      descending long spinal tract fibers arriving at their targets in the spinal gray
      matter, produces characteristic changes in motor output to the muscles that leads
      to the development of new neural strategies for control of segmental and
      plurisegmental neural circuitry. In the second part of this review, we discuss
      available treatment modalities for impaired cord function and briefly outline
      neurobiological interventions under development for repair of spinal cord injury.

PMID- 15853675
TI  - Roles of methionine suldfoxide reductases in antioxidant defense, protein
      regulation and survival.
AB  - One of the most oxidation-sensitive amino acids is methionine. Oxidation of
      methionine to methionine sulfoxide (MetO) could, on the one hand, be an important
      component of signal transduction pathways and on the other hand, may lower the
      cellular antioxidant capacity, alter protein function, interfere with signal
      transduction, and damage proteins. The latter changes could lead to the
      accumulation and malfunction of various proteins. As a result, enhanced
      development of certain diseases and signs of aging may occur. So far, two major
      enzymes that could reduce MetO in proteins have been described, denoted as MsrA
      and MsrB (Methionine sulfoxide reductases). In general, Msrs have been shown to
      be important in protecting cells from oxidative stress throughout many species
      from bacteria to mammals. In addition, the activities of certain enzymes could be
      restored or controlled following reduction of their MetO residues, through the
      Msr system. Of all Msrs, MsrA seems to be important in controlling MetO reduction
      in general and MsrB, thioredoxin reductase (Trr), and the adhesion capabilities
      of certain bacterial cells in particular. The recently discovered MsrB can reduce
      specifically the R-MetO enantiomer while MsrA can reduce specifically the S-MetO
      enantiomer. Another significant difference between MsrA and MsrB is that the
      latter's major form in mammalian cells is a selenoprotein. The current review
      will discuss the major characteristics of methionine sulfoxide reductases as
      physiological antioxidants, repair systems, and cellular regulating enzymes.

PMID- 15853674
TI  - Neural plasticity after spinal cord injury.
AB  - Spinal cord injury (SCI) has devastating physical and socioeconomical impact.
      However, some degree of functional recovery is frequently observed in patients
      after SCI. There is considerable evidence that functional plasticity occurs in
      cerebral cortical maps of the body, which may account for functional recovery
      after injury. Additionally, these plasticity changes also occur at multiple
      levels including the brainstem, spinal cord, and peripheral nervous system.
      Although the interaction of plasticity changes at each level has been less well
      studied, it is likely that changes in subcortical levels contribute to cortical
      reorganization. Since the permeability of the blood-brain barrier (BBB) is
      changed, SCI-induced factors, such as cytokines and growth factors, can be
      involved in the plasticity events, thus affecting the final functional recovery
      after SCI. The mechanism of plasticity probably differs depending on the time
      frame. The reorganization that is rapidly induced by acute injury is likely based
      on unmasking of latent synapses resulting from modulation of neurotransmitters,
      while the long-term changes after chronic injury involve changes of synaptic
      efficacy modulated by long-term potentiation and axonal regeneration and
      sprouting. The functional significance of neural plasticity after SCI remains
      unclear. It indicates that in some situations plasticity changes can result in
      functional improvement, while in other situations they may have harmful
      consequences. Thus, further understanding of the mechanisms of plasticity could
      lead to better ways of promoting useful reorganization and preventing undesirable
      consequences.

PMID- 15853676
TI  - Synthetic glucocorticoids: antenatal administration and long-term implications.
AB  - A clear relationship between intrauterine development and later life
      predisposition to long-term disease is well established. Weight at birth provides
      a surrogate measure for fetal development and low birth weight predicts changes
      in most endocrine axes in adulthood. The exposure of the fetus to elevated levels
      of either endogenous or synthetic glucocorticoids, pre and periconceptional
      nutritional status and immediate postnatal development including catch-up growth
      all contribute substantially to the development of adult onset disease. Fetal
      exposure to high levels of glucocorticoids has direct clinical relevance.
      Synthetic glucocorticoids (betamethasone/ dexamethasone) are administered to
      women at risk of preterm delivery to advance fetal maturation and reduce neonatal
      morbidity and mortality. However, in human pregnancy, evidence suggests that
      fetal exposure to synthetic glucocorticoids has detrimental effects on birth
      outcome, childhood cognition and long-term behavior. Studies in animals have
      established a link between prenatal exposure to synthetic glucocorticoids and
      alterations in fetal development as well as changes in placental function. These
      developmental alterations appear to be permanent. Whether this is the case in
      humans awaits long-term follow-up of children enrolled in randomized controlled
      trials of prenatal glucocorticoid therapy. The research challenges in this field
      are now centered on uncovering the mechanisms by which glucocorticoids are
      involved in programming the fetus for its future life, and discovering ways in
      which the effectiveness and safety of antenatal glucocorticoids can be enhanced.
      The purpose of this mini-review is to provide a background into the use of
      antenatal synthetic corticosteroids and to highlight and summarize recently
      published clinical and animal-based studies.

PMID- 15853678
TI  - Neuroprotection and regeneration strategies for spinal cord repair.
AB  - The journey toward a cure for spinal cord injury (SCI) has taken many paths. In
      this article, we review these paths, and highlight the clinical applications of
      these experimental repair strategies. Initial strategies involved attempts at
      neuroprotection with steroids and other anti-inflammatory drugs. Other anti
      ischemia treatments, agents to eliminate the damage from excitotoxicity, and anti
      apoptotic agents were also tried. Another avenue involved enhancing the function
      of the remaining uninjured axons by measures to produce remyelination and
      medications to improve axonal conduction. In the last two decades there has been
      a major effort to enhance spinal cord axonal regeneration through a variety of
      techniques including neutralization of neurite inhibition, administration of
      neurotrophic factors, implantation of synthetic channels, and transplantation of
      a variety of cell types. Indeed, several of these strategies have been so
      promising in animals that clinicians have been stimulated to explore their
      potential human application. We also examine the different experimental models of
      SCI used to assess repair, and discuss how the injury model impacts on the
      assessment of axonal regeneration and functional recovery after SCI. The
      mechanisms of recovery that may be involved after SCI will be analyzed, and their
      relevance toward finding a cure for human SCI. Unfortunately, the goal of
      producing significant functional regeneration of the human spinal cord has not
      yet been achieved despite the many strategies that have been developed. It is our
      hope that improved understanding of the mechanisms underlying functional recovery
      will lead to successful therapeutic strategies in humans.

PMID- 15853679
TI  - Inflammatory-mediated injury and repair in the traumatically injured spinal cord.
AB  - Spinal cord trauma activates the immune system and elicits leukocyte recruitment
      to the site of injury. This increase in immunological activity contributes to
      acute lesion expansion over a period of days to weeks following the initial
      trauma. At the same time, inflammatory cells and mediators facilitate endogenous
      repair processes such as axonal sprouting and remyelination. Thus, to be
      effective, therapies that target the immune system must limit the destructive
      effects of neutrophil, macrophage and lymphocyte activation, while simultaneously
      preserving their reparative functions.

PMID- 15853680
TI  - Cell elimination as a strategy for repair in acute spinal cord injury.
AB  - Following injury, as part of the wound-healing process, cell proliferation occurs
      mostly to replace damaged cells and to reconstitute the tissue back to normal
      condition/function. In the spinal cord some of the dividing cells following
      injury interfere with the repair processes. This interference occurs at the later
      stages of wound healing (the third week after injury) triggering chronic
      inflammation and progressive tissue decay that is the characteristic pathology of
      spinal cord injury. Specific cell elimination within a critical time window after
      injury can lead to repair in the acutely injured spinal cord. Cell proliferation
      events can be manipulated/modified by x-irradiation. Clinically, numerous
      radiation protocols (i.e., radiation therapy) have been developed that
      specifically eliminate the rapidly dividing cells without causing any
      noticeable/significant damage to the tissue as a whole. Radiation therapy when
      applied within the critical time window after injury prevents the onset of
      chronic inflammation thus leading to repair of structure and function. Various
      aspects of the development of this cell-elimination strategy for repair in acute
      spinal cord injury by utilizing radiation therapy are being reviewed. Topics
      reviewed here: identifying the window of opportunity; and the beneficial repair
      effects of radiation therapy in a transection injury model and in a model
      relevant to human injury, the contusion injury model. The possible involvement of
      cellular components of the blood-spinal cord barrier as the trigger of chronic
      inflammation and/or target of the radiation therapy is discussed.

PMID- 15853681
TI  - Targeting neurite growth inhibitors to induce CNS regeneration.
AB  - Prominent among the several endogenous inhibitors known to limit recovery and
      plasticity after CNS injury are Nogo (neurite outgrowth inhibitor) and MAG
      (myelin associated glycoprotein). The effects of these inhibitors on axonal
      regeneration can be reduced by administration of specific antagonists, some of
      which are commercially available for experimental investigation. There are three
      aspects of therapeutic manipulations: targeting the inhibitory proteins,
      antagonizing the known receptor, and inhibiting the intracellular signal
      transduction of these inhibitory molecules. Infusion of an antibody against Nogo
      improves behavioral deficits and enhances corticospinal tract regeneration in
      animals after stroke and spinal cord injury (SCI). Similarly, peripheral
      injection of a mouse monoclonal antibody directed against MAG results in dramatic
      preferential motor reinnervation in mice after transection of the femoral nerve,
      indicating that interference with the repellant function of MAG facilitates
      reinnervation of correct pathways by motor neurons. Further, antagonism of the
      Nogo receptor by the peptide NEP 1-40 (Nogo extracellular peptide residues 1-40)
      can promote axonal regeneration in rats after SCI. Blockade of signal
      transduction also can be effective. The p75 neurotrophin receptor probably
      represents the signaling part of the receptor complex for neurite growth
      inhibitors. There is evidence in vitro that the inhibitory actions of MAG and
      myelin are blocked if neurons are primed with a variety of neurotrophins. Thus,
      there are several therapeutic approaches to overcome the actions of endogenous
      neurite growth inhibitors so as to promote CNS regeneration.

PMID- 15853682
TI  - Plasticity and therapeutic potential of mesenchymal stem cells in the nervous
      system.
AB  - Mesenchymal stem cells resident in adult bone marrow are best characterized by
      their capacity to differentiate into connective tissue cell types such as
      adipocytes, chondrocytes, osteoblasts and hematopoiesis-supporting stroma.
      Accordingly, these cells are being evaluated in human clinical trials for
      efficacy in treating genetic diseases of bone, to speed hematopoietic recovery
      after bone marrow transplantation and reduce the severity of graft versus host
      disease. In the past few years MSCs have also been reported to exhibit a broad
      degree of plasticity commensurate with other adult stem cell populations,
      including the ability to differentiate in vitro and in vivo into non-mesodermal
      cell types such as neurons and astrocytes. MSCs have also been reported to
      promote repair and regeneration of nervous tissue within the central and
      peripheral nervous system, although the mechanism by which this occurs remains
      indeterminate. Herein, we review evidence purporting the differentiation of MSCs
      into neural cell lineages and evaluate the utility of MSCs as cellular vectors
      for treating neurological disorders and spinal cord injury. Based on our analysis
      of their transcriptome, we also theorize how the varied functions of MSCs and
      their progeny in bone marrow may extrapolate to a therapeutic benefit in models
      of neurological disease.

PMID- 15853683
TI  - Strategies to create a regenerating environment for the injured spinal cord.
AB  - Spine cord injury (SCI) leads to devastating functional loss below the level of
      injury. Partially explained by the presence of a non-permissive environment, the
      injured spinal cord does not mount adequate regeneration to re-establish
      functional connections. Therefore, it is important to identify the cellular and
      molecular factors and their interactions that affect axonal regeneration within
      the changed environment. This review will discuss the current understanding of
      the neuronal and glial factors and the extracellular matrix in the spinal cord
      that inhibit axonal growth, and it will summarize some major approaches for
      facilitation of regeneration. The strategies are classified into the following
      categories: penetration of the blood-brain barrier; modulation of caspase
      activity to reduce apoptosis; stem cells and tissue implantation; administration
      of neurotrophic factors, including viral vector-mediated delivery; and modulation
      of the extracellular matrix. Although recent studies on genomic regulation and
      apoptosis have identified particularly important molecular targets, more is
      necessary to achieve long-term regeneration. A combination of the approaches
      targeting various aspects in the regenerating environment would be more effective
      than a single strategy. Overall, insights arising from the experimental results
      may eventually lead to better therapeutic intervention so as to lessen the
      functional disability and enhance the quality of life in patients with SCI.

PMID- 15853684
TI  - Innate immunity and the heart.
AB  - The immune system of higher vertebrates consists of two components: the innate
      and adaptive immunity. While the adaptive immune system relies on somatically
      generated and clonally selected antigen receptors, the innate immune system
      detects the presence of pathogens by their evolutionarily highly conserved,
      relatively invariant structural motifs. Interestingly, recent data suggest that
      activation of the innate immune system could play an important role in various
      diseases without the direct involvement of infectious pathogens. For example, a
      number of inflammatory cytokines, including TNF (tumor necrosis factor), IL
      (interleukin)-1beta, IL-6 and IL-8, as well as iNOS (inducible nitric oxide
      synthase), all components of innate immunity, are also implicated in
      ischemia/reperfusion injury, and in the abnormal myocardial remodeling
      characteristic of chronic heart failure. Understanding of the regulation and
      activation of the innate immune system in diseases not obviously related to an
      immune response to specific pathogen could provide new therapeutic targets for
      cardiovascular diseases. Thus, in this review, we provide a general overview of
      the components of innate immunity with a focus on humoral factors, their role in
      the response to foreign pathogens, and their potential role in the response to
      tissue injury (i.e., the "Expanded Self-Non-Self" and the "Danger" theories of
      immune activation).

PMID- 15853685
TI  - The reno-protective effect of the dual blockade of the renin angiotensin system
      (RAS).
AB  - Hypertension and proteinuria are risk factors for renal disease progression.
      There is clear evidence that pharmacological blockade of the RAS with angiotensin
      converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB)
      reduces proteinuria and slows down the progression of renal disease in diabetic
      and non diabetic nephropathies, a beneficial effect not related to blood pressure
      control. However, not all patients respond similarly to these treatments. Some
      patients exhibit a significant beneficial response while others do not. The
      absence of response may be explained by the incomplete blockade of the RAS
      obtained with ACEI, which are unable to block completely the formation of AII,
      some generation of AII is produced via other non ACE pathways. In the search of
      new alternatives that could improve the antiproteinuric and nephroprotective
      effects of RAS blockers, the association of ACEI and ARB might prove to be
      useful. ARB produces a complete blockade of the RAS and stimulates the
      vasodilating and non-proliferative actions of AII via the AT-2 receptor.
      Furthermore, ACE inhibitors but not ARB; inhibit the metabolism of kinins, which
      increases the level of bradykinin, a potent vasodilator. Recently, several
      authors have shown a more marked antiproteinuric effect of the dual blockade of
      the RAS versus ACEI or ARB alone in spite of a similar effect on blood pressure.
      A recent study also has demonstrated that this more marked antiproteinuric effect
      is associated with a less progression of renal disease in primary, non diabetic
      nephropathies. Furthermore, at least two studies have shown that, treatment with
      ARB postpones end-stage renal disease and reduces the rate of decline in renal
      function in patients with type 2 diabetes and nephropathy, but until now, there
      is not any clear evidence of a superior beneficial effect of dual blockade versus
      maximal recommended dose of ARB regarding renal progression in type 2 diabetic
      nephropathy, which is the most frequent cause of end stage renal disease. Long
      term clinical trials are needed and encouraged to further establish the
      significant role of dual blockade in renal protection particularly in diabetic
      nephropathy.

PMID- 15853686
TI  - Phospholipase A2 inhibitors as potential anti-inflammatory agents.
AB  - Phospholipase A(2) (PLA(2))-catalyzed hydrolysis of membrane phospholipids
      results in the stoichiometric production of a free fatty acid, most importantly
      arachidonic acid, and a lysophospholipid. Both of these phospholipid metabolites
      serve as precursors for inflammatory mediators such as eicosanoids or platelet
      activating factor (PAF). Since it was initially discovered that non-steroidal
      anti-inflammatory drugs inhibit prostaglandin synthesis, a vast amount of drug
      development has been performed to selectively inhibit the production of the
      inflammatory metabolites of arachidonic acid while preserving their protective
      role. This research has culminated in the development of selective cyclooxygenase
      2 (COX-2) inhibitors that act on the inducible, inflammatory COX enzyme, but do
      not affect the constitutive prostaglandin synthesis in cells that is mediated via
      COX-1. The development of PLA(2) inhibitors as potential anti-inflammatory agents
      has also been extensively pursued since the release of arachidonic acid from
      membrane phospholipids by PLA(3) is one of the rate-limiting factors for
      eicosanoid production. In addition to the production of eicosanoids, PLA(2)
      catalyzed membrane phospholipid hydrolysis is also the initiating step in the
      generation of PAF, a potent inflammatory agent. Thus, inhibition of PLA(2)
      activity should, in theory, be a more effective anti-inflammatory approach.
      However, developing an inhibitor that would be selective for the production of
      inflammatory metabolites and not inhibit the beneficial properties of PLA(2) has
      so far proved to be elusive. This review will focus on agents used currently to
      inhibit PLA(2) activity and will explore their possible therapeutic use.

PMID- 15853687
TI  - Targeting kinin receptors for the treatment of neurological diseases.
AB  - Kinins (bradykinin, kallidin and their active metabolites) are peptide autacoids
      with established functions in cardiovascular homeostasis, contraction and
      relaxation of smooth muscles, inflammation and nociception. They are believed to
      play a role in disease states like asthma, allergies, rheumatoid arthritis,
      cancer, diabetes, endotoxic and pancreatic shock, and to contribute to the
      therapeutic effects of ACE inhibitors in cardiovascular diseases. Although kinins
      are also neuromediators in the central nervous system, their involvement in
      neurological diseases has not been intensively investigated thus far. This review
      analyzes the potential of central kinin receptors as therapeutic targets for
      neurological disorders. Initial data highlight potential roles for B(1) receptor
      antagonists as antiepileptic agents, and for B(2) receptor antagonists (and/or
      B(1) agonists) in the treatment of stroke. Functional B(1) receptors located on T
      lymphocytes and on the blood brain-barrier are also putative targets for the
      management of multiple sclerosis. However, successful elucidation of the
      therapeutic value of these new pharmacological approaches will require refinement
      of our knowledge on the physiology and cellular localization of central kinin
      receptors.

PMID- 15853688
TI  - The role of alterations in arachidonic acid metabolism and nitric oxide
      homeostasis in rat models of diabetes during early pregnancy.
AB  - The diabetic pathology induces reproductive abnormalities that enhance
      spontaneous abortion, congenital anomalies and neonatal morbidity/mortality
      rates, abnormalities that begin with an altered female gamete. In this review we
      focus on the damage induced by maternal hyperglycemia during ovulation, early
      embryo development, implantation and embryo organogenesis in experimental rat
      models of diabetes. Hyperglycemia can induce cellular damage by enhancing the
      production of reactive oxygen species (ROS), by altering arachidonic acid
      metabolism (thus leading to altered production of prostaglandins such us
      PGE(2)and 15deoxydelta(12-14)PGJ(2), involved in signalling and developmental
      pathways), and by enhancing the generation of nitric oxide (a mediator of many
      cell functions including apoptotic cell death). In maternal diabetes all of these
      abnormalities are present from the oocyte stage, during embryonic implantation,
      and during embryo organogenesis. The involvement of these alterations in embryo
      loss and congenital malformations due to diabetes and the cross-talk among these
      metabolic pathways are discussed. As maternal hyperglycemia induces damage from
      the oocyte stage and throughout embryo development the data reviewed suggests the
      need of strict preconceptional metabolic control. The importance of the molecules
      involved in hyperglycemia-induced damage as future pharmacological targets for
      intervention is discussed.

PMID- 15853689
TI  - Opioids: old drugs for potential new applications.
AB  - Opioids are commonly used analgesics in clinical practice. Three opioid receptors
      (mu, delta and kappa) that mediate opioid effects have been identified by
      molecular cloning. Each type of opioid receptors consists of subtypes of
      receptors as suggested by pharmacological studies. Although mu opioid receptors
      are the major receptor to mediate the analgesic effects of opioids, delta and
      kappa receptors are also important in anti-nociception (for example, delta and
      kappa receptors can mediate spinal analgesia). Recently, the cytoprotective
      effects of opioids have been recognized. The presence of opioids during harmful
      events such as ischemia reduces cell injury in multiple organs including heart
      and brain. These effects appear to be mediated by delta receptors in most
      studies. A new form of cytoprotection in which a prior exposure to opioids
      renders protection against cell ischemia (opioid preconditioning) has been
      identified. In the heart, this opioid preconditioning-induced protection has been
      well documented by multiple studies and may be mediated by delta receptors,
      G(i/o) proteins, protein kinase C, ATP-sensitive potassium channels and free
      radicals. Our initial study suggests that opioid preconditioning also induces
      neuroprotection. This neuroprotection involves delta(1) receptors, mitochondrial
      ATP-sensitive potassium channels and free radical production. In this review, we
      will briefly describe the analgesic effects of opioids. We will focus our
      discussion on opioid preconditioning-induced protection and its mechanisms.
      Opioids and agents that specifically work on the signaling molecules for opioid
      preconditioning-induced protection may prove to be useful in inducing protection
      against ischemia in clinical practice.

PMID- 15853690
TI  - NMR spectroscopy and protein structure determination: applications to drug
      discovery and development.
AB  - Recent technological advances in NMR methods and instrumentation are having a
      significant impact in structural biology. These innovations are also impacting
      pharmaceutical biotechnology as it is now possible to use NMR spectroscopy to
      rapidly characterize a growing number of prospective protein drugs and protein
      drug targets. This review provides a general summary of how solution-state NMR
      can be used to determine protein structures. It also focuses on exploring how
      advances in solution state NMR are changing the way in which protein structures
      can be determined and protein-ligand interactions can be characterized. Recent
      innovations in protein sample preparation, in instrumentation and data
      collection, in spectral assignment and in structure generation are highlighted.
      The impact of solution-state NMR on pharmaceutical biotechnology is also
      discussed, with a special emphasis on describing how NMR has been used to study a
      number of pharmaceutically important proteins and how NMR is currently being used
      to rapidly screen and to map the binding sites of small molecules to a range of
      protein targets.

PMID- 15853691
TI  - Release kinetics from bio-polymeric nanoparticles encapsulating protein synthesis
      inhibitor- cycloheximide, for possible therapeutic applications.
AB  - Cycloheximide, a protein synthesis inhibitor, was encapsulated in cross-linked
      gelatin nanoparticles (Type B, Bovine skin, 75 Bloom) of 168 nm diameter with 26%
      entrapment efficiency. In-vitro release kinetics of the drug from the
      nanoparticles was done in phosphate buffer saline (PBS) at pH 7.4 and pH 5.8. The
      release kinetics showed a bi-phasic curve. Interestingly, the release of drug is
      approx 90% in acidic pH as compared to 50% release in neutral pH. The particle
      size was determined by Dynamic Light Scattering (DLS) technique, and size
      distribution spectra at different pH were observed to vary inversely with
      increase in pH. These drug loaded nanoparticles were found to be stable in whole
      blood showing negligible haemolysis. Cytotoxicity in HBL-100 and MCF-7, breast
      cancer cell lines was done in a 24-72 hrs assay, showing increased anti-tumour
      activity over a period of time indicating slow release. Dose dependent
      cytotoxicity was observed after 24 hours upto 72 hours of incubation of
      nanoparticles while the drug per se (<4 microg) showed 93% toxicity within 24
      hours. Phase contrast microscopy of nanoparticle-cell interaction, clearly
      indicated aggregation along the lipid cell-membrane. Electron Microscopy (TEM,
      SEM) studies revealed its size and spherical shape. The stability of the
      particle, the slow and controlled release of drug from the gelatin nanoparticles
      indicate that it is a good candidate to deliver bio-pharmaceuticals. These behave
      as "intelligent" carriers for drug delivery, and can be exploited to empty their
      drug load in acidic medium. The paper focuses on the release kinetics of the
      gelatin nanoparticles that can be successfully exploited to treat solid tumors.

PMID- 15853692
TI  - Targeting therapeutic and imaging agents to folate receptor positive tumors.
AB  - The membrane-bound folate receptor (FR) is overexpressed on a wide range of human
      cancers, such as those originating in ovary, lung, breast, endometrium, kidney
      and brain. The vitamin folic acid is a high affinity ligand of the FR which
      retains its receptor binding properties when conjugated to other molecules.
      Consequently, "folate targeting" technology has successfully been applied for the
      delivery of protein toxins, chemotherapeutic agents, radio-imaging and
      therapeutic agents, MRI contrast agents, liposomes, gene transfer vectors,
      antisense oligonucleotides, ribozymes and immunotherapeutic agents to FR-positive
      cancers. These folate-bearing delivery systems have produced major enhancements
      in cancer cell specificity and selectivity over their non-targeted formulation
      counterparts. Hence, it is hopeful that this targeting strategy will lead to
      improvements in the safety and efficacy of clinically-relevant anti-cancer
      agents. Therefore, the focus of this review will be to highlight the current
      status of folate-targeted technology with particular emphasis on the recent
      advances in this field as well as possible directions for future development.

PMID- 15853693
TI  - Diffusion behavior of gap junction hemichannels in living cells.
AB  - Due to its non-invasive character, fluorescence correlation spectroscopy (FCS) is
      particularly suited for the investigation of diffusion behavior of proteins in
      living cells. In this study we have investigated the diffusion properties of CFP
      labeled gap junction hemichannels in the plasma membrane of living HeLa cells.
      Gap junction hemichannels or connexons are the precursors for the cell-cell- or
      gap junction channels that form large plaques at the contact areas between two
      adjacent cells. It has been proposed that new channels are recruited into a gap
      junction structure from a pool of hemichannels that can freely diffuse over the
      entire plasma membrane. The statistical approach shows that the geometry of the
      membrane within the focus is the most important property for the form of the
      autocorrelation curve and in turn for the determination of the diffusion
      coefficient. On the other hand binding-unbinding events which lead to anomalous
      diffusion have only a minor effect to the position and shape of the correlation
      curve compared to the geometry of the membrane.

PMID- 15853694
TI  - Analysis of cellular functions by multipoint fluorescence correlation
      spectroscopy.
AB  - The biophysical investigation of living cells is currently possible by single
      molecular detection methods such as fluorescence correlation spectroscopy (FCS).
      FCS is applied for measuring the dynamic mobility of target molecules in living
      cells; however, the conventional FCS systems still lack quantitative analysis for
      many regions of interests (ROI) in real time. To improve this situation, we have
      developed a novel multipoint FCS system (M-FCS) that can measure multipoint
      correlation functions in the cell simultaneously. To evaluate its performance, we
      measured correlation functions for rhodamine 6G (Rh6G) in homogeneous conditions
      and for green fluorescence protein (GFP) in HeLa cells. We conclude that M-FCS
      possesses reliable performance. As a pharmacological application, glucocorticoid
      receptor protein fused GFP (GR-GFP) was transfected in HeLa cells and FCS
      measurements were carried out in the cytoplasm and the nucleus simultaneously.
      The translocation of GR-GFP from the cytoplasm to the nucleus by ligand
      stimulation was observed with laser scanning microscopy (LSM) and M-FCS.
      Particularly in the nucleus, the slower diffusion of GR-GFP suggested molecular
      interactions after the translocation. These data imply that M-FCS can be applied
      for quantitative analysis of kinetic processes in living cells.

PMID- 15853695
TI  - Prion disease: a deadly disease for protein misfolding.
AB  - An infectious particle, termed prion, composed largely and perhaps solely of a
      single protein, is the likely causative agent of prion disease. It produces
      lethal decline of cognitive and motor function. The responsible protein arrives
      at a pathogenic state by misfolding from a normal form that has ubiquitous tissue
      distribution. Prion diseases are often called spongiform encephalopathies.
      Probably most mammalian species develop these diseases. Specific examples in
      various animals are -Scrapie, Transmissible Mink Encephalopathy (TME ), Chronic
      Wasting Disease(CWD) and bovine spongiform encephalopathy (BSE). Humans are also
      susceptible to several prion diseases: Creutzfeld-Jacob Disease (CJD), Gerstmann
      Straussler-Scheinker Syndrome (GSS), Fatal Familial Insomnia (FFI), Kuru and
      Alpers Syndrome. This paper reviews transmission of this diseases, protein
      involvement, nature of protein, the conversion process from PrP(c) to PrP(Sc),
      conversion of prion protein in vitro, the different proposed models for the
      conversion of PrP(c) to PrP(Sc), prion and other amyloid diseases, prion strains,
      structure of PrP(c) the particular process that may induce prion disease, and
      immunization against these diseases.

PMID- 15853696
TI  - Natriuretic peptide family: new aspects.
AB  - Thus far, five molecules comprise the natriuretic peptide family (NPF): ANP,
      urodilatin, BNP, CNP and DNP. Precursor hormones for ANP, BNP and CNP are encoded
      by a different gene. Final peptides are ligands for A, B and C receptors, acting
      the latter as a clearance receptor besides neutral endopeptidase (EC 24.11). cGMP
      acts as a second messenger. Natriuretic peptides (NP) have well-known functions
      such as natriuretic, antihypertensive and reduction of plasma renin-aldosterone
      concentrations. An antiinflammatory ANP potential and a pro-apoptotic action in
      rats endothelial cells of different NP have been described. Unlike adults, NP
      show a different distribution during ontogeny and a different pattern of
      excretion under different stimuli. Noncompetitive immunoassays have become more
      suitable than competitive ones for routine measurement of NP with recent advances
      in speed of measurement. BNP and pro-BNP are emerging as useful tools in
      diagnosis, management and prognosis of heart disease. Preliminary data support a
      role of NP in the therapy of congestive heart failure. Finally, potential
      therapeutic compounds of NP in different pathologies are updated with an
      important focus on vasopeptidase inhibitors. These are capable of strengthening
      NP and inhibiting renin-angiotensin system at the same time, as potential useful
      molecules in cardiovascular therapy.

PMID- 15853697
TI  - Recent development of peptides from glycoproteins IIb (alphaIIb) and IIIa (beta3)
      that inhibit platelet fibrinogen binding.
AB  - The glycoprotein (GP) IIb/IIIa (alphaIIbbeta3) found on platelets binds
      fibrinogen when platelets are activated, thereby mediating the platelet
      aggregation process. Blockading of alphaIIbbeta3 has been proposed to prevent
      platelet aggregation independent of the substance(s) responsible for activating
      the platelets. This inhibition of platelet aggregation is thought to be an
      effective therapeutic approach to various thromboembolic syndromes. The
      development of various forms of alphalambdapietaalpha;IIbbeta3 inhibitors has
      resulted in the inhibition of platelet aggregation, although studies of
      alphaIIbbeta3 receptor function and various alphaIIbbeta3 inhibitors have
      demonstrated the potential for these agents to produce effects on other aspects
      of platelet function as well as having non-platelet effects. This review
      describes the newly derived peptides from 1) glycoprotein IIb (alphaIIb) that
      interferes with platelet aggregation by inhibiting the binding of fibrinogen to
      alphaIIbbeta3 and from 2) GP IIIa (beta3) by blocking the alphaIIbbeta3 complex
      formation. These peptides may become effective agents to block the interaction of
      ADP, type I collagen, and type III collagen (type I collagen and type III
      collagen are present in abundant amounts in blood vessel walls) with platelets.

PMID- 15853698
TI  - Molecular predictors of drug-induced prolongation of the QT interval.
AB  - One of the most common causes of drug withdrawal from the market is the
      prolongation of the QT interval associated with polymorphic ventricular
      tachycardia or torsade de pointes (TdP) that can degenerate into ventricular
      fibrillation and sudden cardiac death. Cardiac and non-cardiac drugs prolong the
      QT interval and cause TdP by blocking cardiac K+ channels in general, and
      selectively blocking the rapidly activating delayed rectifier channel IKr. Co
      assembly of HERG (human-ether-a-go-go-related gene) alpha-subunits and MiRP1
      (MinK-related peptide 1) beta-subunits recapitulate the behavior of native human
      IKr, and the majority of mutations of HERG and MiRP1 decrease the repolarizing
      current, delay ventricular repolarization and prolong the QT. Thus, drug-induced
      QT prolongation and TdP might represent an iatrogenic reproduction of the
      congenital long-QT syndrome (LQTS). Current evidence suggests that 5 to 10% of
      persons in whom TdP develops on exposure to QT-interval prolonging drugs harbor
      mutations associated with the LQTS and can therefore be viewed as having a
      subclinical form of the congenital syndrome. This clinical observation is
      entirely consistent with the concept of reduced repolarization reserve arising
      from a mutation in an ion-channel gene, which predisposes the carrier to drug
      induced TdP. This review centers on the possible molecular mechanisms underlying
      drug-induced QT prolongation and TdP, the description of specific drugs and risk
      factors facilitating the development of TdP, and the recommendations for
      preventing and treating this potentially fatal arrhythmia.

PMID- 15853699
TI  - The multifunctional protein C system.
AB  - The protein C pathway is a major regulator of blood coagulation, since it
      controls the conversion of prothrombin to thrombin through a feedback inhibition
      mechanism. Protein C circulates in plasma as an inactive zymogen and is activated
      on the surface of endothelial cells by the thrombin-thrombomodulin complex, a
      process that can be further enhanced when protein C binds to its membrane
      receptor, the endothelial-cell protein C receptor. Activated protein C (APC) is
      then released from the complex, binds protein S and inhibits thrombin formation
      by inactivating coagulation factors Va and VIIIa. The importance of the protein C
      anticoagulant pathway is emphasized by the increased risk of venous
      thromboembolism (VTE) associated with protein C and protein S deficiencies, the
      factor V Leiden mutation, and reduced circulating APC levels. The protein C
      pathway also plays a significant role in inflammatory processes, since it
      prevents the lethal effects of E. coli-associated sepsis in animal models and
      improves the outcome of patients with severe sepsis. APC seems to display anti
      apoptotic and neuroprotective activities. Thus, it reduces organ damage in animal
      models of sepsis, ischemic injury, endothelial cell injury, or stroke. Further
      research will hopefully widen the current therapeutic perspectives in all these
      illnesses, where these effects might play a crucial role in their treatment. This
      review will summarize the mechanisms that contribute to these biological
      activities of the protein C pathway.

PMID- 15853700
TI  - Angiotensin II type I receptor blocker and endothelial function in humans: role
      of nitric oxide and oxidative stress.
AB  - Recent large clinical trials have shown that angiotensin II type I receptor
      blockers (ARBs) reduce cardiovascular morbidity and mortality in patients with
      heart failure, acute myocardial infarction, and hypertension. However, the
      mechanism underlying antiatherogenic effects of ARBs remains unclear. The
      vascular endothelium is involved in the release of various vasodilators,
      including nitric oxide (NO), prostacyclin, and endothelium-derived
      hyperpolarizing factor as well as vasoconstrictors. NO plays an important role in
      the regulation of vascular tone, the inhibition of platelet aggregation, and the
      suppression of smooth muscle cell proliferation. Several investigators have
      reported impairment in endothelium-dependent vasodilation in the forearm,
      coronary, and renal vasculature in cardiovascular diseases, including
      hypertensive patients. Cardiovascular diseases are associated with alteration in
      endothelial function. Endothelial dysfunction is the initial step in the
      pathogenesis of atherosclerosis. Anti-renin-angiotensin system agents,
      angiotensin-converting enzyme (ACE) inhibitors improve endothelial function in
      patients with hypertension, diabetes mellitus, and coronary artery disease. It is
      well known that ACE inhibitors augment endothelium-dependent vasodilation through
      an increase in NO bioavailability, by an increase in NO production and a decrease
      in NO inactivation. ARBs are also thought to prevent cardiovascular complications
      through an augmentation of endothelial function. In this review, we focus on
      recent findings and putative mechanisms of the beneficial effects of ARBs on
      endothelial function.

PMID- 15853701
TI  - Chronic heart failure- potential for pharmacological intervention.
AB  - Heart failure is commonly associated with vascular diseases and a high rate of
      athero-thrombotic events, but the risks and benefits of antithrombotic therapy
      are unknown. The incidence of thromboembolism in heart failure patients (which
      may include stroke, peripheral embolism, pulmonary embolism) seems to be around
      2%, based on the data available from several small studies. However, the
      incidence of thromboembolism should greatly depend upon what is being looked at
      in each of these studies, as it will (generally) not be individually categorised.
      There is very little true epidemiological data to base this figure. The
      pathophysiology of heart failure is complex. There are many well- recognised
      factors, which are associated with thrombosis in heart failure patients, such as
      vascular abnormalities, increased coagulability and impaired blood flow. In the
      past 50 years, many studies have been performed to find out if oral
      anticoagulation is of benefit for the prevention of thromboembolism in patients
      with heart failure. Expert therapeutic guidelines in the Europe and North America
      agree that there is insufficient evidence to recommend that antithrombotic
      therapy should be given to patients with heart failure, unless they have atrial
      fibrillation or, perhaps, a previous thrombo-embolic episode. There is a lack of
      evidence for any antithrombotic agent that is effective in patients with heart
      failure; therefore, randomised clinical trials need to be designed to test the
      hypothesis that patients with chronic heart failure would have benefit from
      anticoagulant therapy. This review summarises the incidence, potential mechanism
      and therapeutic approaches for the management of thromboembolism in heart
      failure.

PMID- 15853702
TI  - Prostacyclin synthase gene: genetic polymorphisms and prevention of some
      cardiovascular diseases.
AB  - Prostacyclin (PGI2) inhibits platelet aggregation and vasoconstriction.
      Prostacyclin synthase (PGIS), a catalyst of PGI2 synthesis from prostaglandin H2,
      is widely distributed and predominantly found in vascular endothelial and smooth
      muscle cells. The PGIS gene is localized to 20q13.11-13, and a candidate gene for
      cardiovascular disease. We discovered mutations and polymorphisms in this gene
      and reported that they were associated with essential hypertension, myocardial
      infarction and cerebral infarction. These results suggest that PGI2 function
      depends on the different alleles of the PGIS gene and that they may influence the
      risk of cardiovascular diseases. Thus, individualized management strategies, such
      as administration of PGI2 analog, could be selected for variants of this gene to
      help prevent the development of cardiovascular diseases.

PMID- 15853703
TI  - Ethiopathogenesis, diagnosis and prevention of vascular calcification in end
      stage renal disease.
AB  - Extensive atherosclerosis and heavy vascular and valvular calcifications are
      common complications of end stage renal disease (ESRD) and are very likely
      related to the high incidence of cardiovascular disease in these patients. The
      greatly increased incidence of cardiovascular disease is only partly explained by
      traditional risk factors for atherosclerosis. In ESRD, vascular calcification
      occurs both in the vascular intima layer and in the tunica media. Intimal
      calcification is disseminated and is characteristically associated with damaged
      and abnormally functioning endothelium, and macrophage and vascular smooth muscle
      cell (VSMC) infiltration typical of atherosclerosis. On the contrary, medial
      calcification occurs in patchy distribution and the most frequent cell types
      found in its vicinity are the VSMC and macrophage. The uremic state is associated
      with numerous metabolic abnormalities and endocrine disturbances primarily
      involving calcium and phosphorus metabolism. Furthermore, chronic kidney disease
      and dialysis are considered states of active and strong inflammatory response.
      These dysfunctions occur early in the course of renal failure and likely
      contribute to the development and progression of vascular calcification and
      atherosclerosis. For many years, vascular calcification was considered solely the
      result of a passive deposition of hydroxyapatite crystals in the arterial wall
      due to elevated calcium-phosphate ion product. However, a large body of evidence
      has now shown that this is a highly regulated process governed by factors that
      closely resemble calcium deposition in bone tissue. In fact, vascular
      calcification requires changes in the phenotype of VSMC and the expression of
      several proteins normally involved in bone metabolism. This review is centered on
      the etiopathogenesis of vascular calcification in ESRD, its detection with modern
      imaging modalities and the therapeutic approaches currently available to slow its
      progression.

PMID- 15853704
TI  - Simple coumarins and analogues in medicinal chemistry: occurrence, synthesis and
      biological activity.
AB  - Coumarins, also known as benzopyrones, are present in remarkable amounts in
      plants, although their presence has also been detected in microorganisms and
      animal sources. The structural diversity found in this family of compounds led to
      the division into different categories, from simple coumarins to many other kinds
      of policyclic coumarins, such as furocoumarins and pyranocoumarins. Simple
      coumarins and analogues are a large class of compounds that have attracted their
      interest for a long time due to their biological activities: they have shown to
      be useful as antitumoural, anti-HIV agents and as CNS-active compounds.
      Furthermore, they have been reported to have multiple biological activities
      (anticoagulant, anti-inflammatory), although all these properties have not been
      evaluated systematically. In addition, their enzyme inhibition properties,
      antimicrobial and antioxidant activities are other foremost topics of this field
      of research. The present work is to survey the information published or
      abstracted from 1990 till 2003, which is mainly related to the occurrence,
      synthesis and biological importance of simple coumarins and some analogues, such
      as biscoumarins and triscoumarins. Data are also highlighted, concerning the
      development of new synthetic strategies that could help in drug design and in the
      work on SAR or QSAR.

PMID- 15853705
TI  - Matrix metalloproteinases in coronary artery disease: clinical and therapeutic
      implications and pathological significance.
AB  - Matrix metalloproteinases (MMP) and their inhibitors (TIMP) are central factors
      in the control of extracellular matrix turnover. They are important in normal
      physiology and also during a range of pathological states. Only recently has
      their role in cardiovascular disease been explored and their analysis through
      measurements in blood been studied. We have systematically identified clinical
      articles relevant to coronary artery disease from the last 10 years using
      MEDLINE. In this review we outline the structure, function and regulation of
      metalloproteinases and their key roles in angiogenesis, stable and unstable
      coronary artery disease. Metalloproteinases and their inhibitors are fundamental
      mediators of change in aging and atherosclerosis, the cell membrane, and in
      myocardial and vascular tissue. Defining their overall importance and
      understanding their complex interrelationships with pressure, thrombosis and
      local neural and hormonal tone will require detailed clinical study. The
      modulation of MMP and TIMP activity using drugs that affect the expression and
      function of these proteins will provide us with new ways to treat these serious
      and disabling diseases, and we explore potential mechanisms and treatments.

PMID- 15853706
TI  - Recent advances in the chemistry and pharmacological activity of new steroidal
      antiandrogens and 5 alpha-reductase inhibitors.
AB  - The object of this paper is to summarize for the past two years the most recent
      development in the field of prostate cancer and 5 alpha-reductase inhibitors. In
      addition we are also including some results on the synthesis and pharmacological
      evaluation of new steroidal compounds developed in our laboratory. Most of the
      new steroidal derivatives are based on the progesterone skeleton and showed a
      high inhibitory activity for the enzyme 5 alpha-reductase. Presently, similar
      compounds are used for the treatment of androgen dependent diseases such as:
      hirsutism, androgenic alopecia, benign prostatic hyperplasia and prostate cancer.
      Dihydrotestosterone 2 (Fig. 1) a 5 alpha-reduced metabolite of testosterone 1 has
      been implicated as a causative factor for the progression of these diseases,
      largely through the clinical evaluation of males who are genetically deficient of
      the enzyme steroid 5 alpha-reductase. As a result of this study, the inhibition
      of this enzyme has become a pharmacological strategy for the design and synthesis
      of new antiandrogenic drugs. The advent of finasteride 7 (Fig. 3) a 5 alpha
      reductase inhibitor has greatly alleviated the symptoms associated with benign
      prostatic hyperplasia. In our laboratory, we recently synthesized several new 16
      beta-methylpregnadiene-3,20-diones: 40, 41 (Fig. 8), 16 beta-phenylpregnadiene
      3,17a-dione derivatives 46 and 47 (Fig. 9) and 49 (C-4 bromoderivative) (Fig.
      11), 52-56 (Fig. 13). The analogue pregnatriene derivatives were also prepared:
      44, 45 (Fig. 9) 50, 51 (Fig. 11) and 57-60 (Fig. 13) These compounds were
      evaluated as 5 alpha-reductase inhibitors in the following biological models:
      Penicillium crustosum broths, the flank organs of gonadectomized male hamsters,
      the incorporation of radiolabeled sodium acetate into lipids, the effect of the
      new steroids on the reduction of the weight of the seminal vesicles and on the in
      vitro metabolism of [3H]T to [3H]DHT in seminal vesicles of homogenates of
      gonadectomized male hamsters. All trienones 44, 45, 50, 51 and 57-60 in all
      biological models showed consistently a higher 5 alpha-reductase inhibitory
      activity than the corresponding dienones: 40, 41, 46, 47, 49 and 52-56. We
      believe that with these compounds the 5 alpha-reductase enzyme is inactivated by
      an irreversible Michael type addition of the nucleophilic portion of the enzyme
      to the conjugated double bond of the steroid. The trienones having a more
      coplanar structure react faster with the enzyme thus showing a higher inhibitory
      activity.

PMID- 15853707
TI  - Recent developments in the identification of chemotherapeutics for Chagas
      disease.
AB  - Chagas Disease, caused by the T. cruzi parasite, is one of the largest public
      health problems in the Western hemisphere. Although its spread has diminished due
      to vector eradication programs, effective chemotherapeutics for the disease
      itself remain elusive. Many efforts towards the development of antiparasitic
      agents active against a number of targets have been described recently in the
      literature. This review summarizes developments in trypanosidal agents from 2000
      through 2003.

PMID- 15853708
TI  - Yeast system as a screening tool for pharmacological assessment of g protein
      coupled receptors.
AB  - G-protein-coupled receptors (GPCRs) constitute the largest but the most divergent
      class of cell surface proteins. Although they are thought to share a common 3D
      structure composed of seven transmembrane helical domains, they can be activated
      by extracellular signals as diverse as light, peptides, proteins, lipids, organic
      odorants, taste molecules, nucleotides or nucleosides. They are involved in an
      extraordinarily large number of physiological functions and are therefore
      potential drug targets for many human diseases. During the last decade various
      GPCRs have been successfully expressed in S. cerevisiae. Yeast is an attractive
      expression system because it offers the genetic engineering tools typical of a
      microorganism while possessing an eukaryotic type of secretory pathway and post
      translational machinery. This host is particularly attractive for in-vivo
      manipulation of these receptors due to the high homology between the yeast
      pheromone signaling pathway and that of mammalian GPCRs. When expressed in yeast,
      mammalian GPCRs have been shown to couple functionally to either the endogenous
      yeast Galpha (Gpa1), or co-expressed mammalian Galpha subunits (wild-type or
      chimeric), and are characterized by a similar pharmacology in response to
      agonists or antagonists as in native cells. Heterologous expression of wild type
      or mutant GPCRs in S. cerevisiae allows a rapid assessment of their ability to
      detect and transduce extracellular stimulations, through the use of a reporter
      system. Furthermore, this approach is amenable to high-throughput screening of
      new drugs, which would provide a determinant advantage in the field of
      therapeutic research, and also for investigation of the still unknown ligands of
      orphan receptors. This review will focus on the latest developments of yeast
      based technology to screen for potential GPCR agonists/antagonists.

PMID- 15853709
TI  - The therapeutic potential of inhibitors of dipeptidyl peptidase IV (DPP IV) and
      related proline-specific dipeptidyl aminopeptidases.
AB  - In this review the structural and functional aspects of dipeptidyl peptidase IV
      (DPP IV) will be described, and the therapeutic potential of DPP IV inhibitors
      will be highlighted. DPP IV will be situated in clan SC, a group of serine
      proteases that contains several proline specific peptidases. Structural aspects
      of DPP IV and its interaction with different types of inhibitors are recently
      revealed by the publication of several crystal structures. Especially the design
      and development of new DPP IV inhibitors based on the three-dimensional
      structure, substrate specificity and catalytic mechanism will be discussed. In
      the last years there was an important development of new pyrrolidine-2-nitriles
      with very promising therapeutic properties for the treatment of type 2 diabetes.
      The role of DPP IV in peptide metabolism of members of the PACAP/glucagon peptide
      family, neuropeptides and chemokines has been thoroughly investigated during
      recent years. This is directly related to the promising therapeutic potential of
      DPP IV inhibitors in the treatment of type 2 diabetes and in the treatment of
      immunological disorders. Several inhibitors are currently under investigation in
      clinical trials for the treatment of type 2 diabetes and represent a new class of
      drugs for the treatment of this disease.

PMID- 15853710
TI  - Gadolinium meets medicinal chemistry: MRI contrast agent development.
AB  - Magnetic resonance imaging (MRI) contrast agents are utilized adjunctively to
      enhance the contrast between normal and abnormal structures on MRI scans. Along
      with the rapid evolution of the field has come a new appreciation for the
      medicinal chemistry of this unique class of metallopharmaceuticals. The efficacy
      of MRI agents is a complex function of chemical, biophysical, and pharmacological
      properties, which must be married in a package of exquisite safety. This report
      illustrates the wide range of medicinal chemistry relevant to existing agents
      that are either approved or in clinical development, as well as concepts, which
      may result in exciting new pharmaceuticals in the future.

PMID- 15853711
TI  - Scintigraphic imaging of gene expression and gene transfer.
AB  - Assessment of gene function following the completion of human genome sequencing
      can be performed with nuclear medicine procedures. These techniques may be
      applied for the determination of gene function and regulation using established
      and new tracers or using in vivo reporter genes such as genes encoding enzymes,
      receptors, antigens, or transporters. Visualization of in vivo reporter gene
      expression can be done using radiolabeled substrates, antibodies, or ligands.
      Combinations of specific promoters and in vivo reporter genes may deliver
      information about the regulation of the corresponding genes. The role of
      radiolabeled antisense molecules for the analysis of mRNA content has to be
      investigated. However, possible applications are therapeutic interventions using
      triplex oligonucleotides with therapeutic isotopes, which can be brought near to
      specific DNA sequences to induce DNA strand breaks at selected loci. Imaging of
      labeled siRNA's makes sense if these are used for therapeutic purposes in order
      to assess the delivery of these new drugs to their target tissue.
      Pharmacogenomics will identify new surrogate markers for therapy monitoring which
      may represent potential new tracers for imaging.

PMID- 15853712
TI  - Fluorescence imaging of tumors in vivo.
AB  - We review recent progress in tumor imaging in vivo using fluorescent tags,
      highlight the problems of fluorescence imaging in small animals, discuss recent
      advances in near-infrared fluorochromes and quantum dots, and point to some
      future possibilities. GFP-based fluorescence imaging is briefly discussed. The
      authors believe that improvements in near-infrared fluorochromes are required to
      enable practical imaging in tissues at centimeter depths.

PMID- 15853713
TI  - Positron-emitting isotopes produced on biomedical cyclotrons.
AB  - This review will discuss the production and applications of positron-emitting
      radionuclides for use in Positron Emission Tomography (PET), with emphasis on
      radionuclides that can be produced onsite with a biomedical cyclotron. In PET the
      traditional radionuclides of choice are (11)C, (113)N, (15)O and (18)F and
      although they will be briefly discussed in this article, the emphasis of this
      review will be on 'non-standard' PET radionuclides that are generating increased
      interest by the medical research community.

PMID- 15853714
TI  - 19F: a versatile reporter for non-invasive physiology and pharmacology using
      magnetic resonance.
AB  - The fluorine atom provides an exciting tool for diverse spectroscopic and imaging
      applications using Magnetic Resonance. The organic chemistry of fluorine is
      widely established and it can provide a stable moiety for interrogating many
      aspects of physiology and pharmacology in vivo. Strong NMR signal, minimal
      background signal and exquisite sensitivity to changes in the microenvironment
      have been exploited to design and apply diverse reporter molecules. Classes of
      agents are presented to investigate gene activity, pH, metal ion concentrations
      (e.g., Ca(2+), Mg(2+), Na(+)), oxygen tension, hypoxia, vascular flow and
      vascular volume. In addition to interrogating speciality reporter molecules,
      (19)F NMR may be used to trace the fate of fluorinated drugs, such as
      chemotherapeutics (e.g., 5-fluorouracil, gemcitabine), anesthetics (e.g.,
      isoflurane, methoxyflurane) and neuroleptics. NMR can provide useful information
      through multiple parameters, including chemical shift, scalar coupling, chemical
      exchange and relaxation processes (R1 and R2). Indeed, the large chemical shift
      range (approximately 300 ppm) can allow multiple agents to be examined,
      simultaneously, using NMR spectroscopy or chemical shift selective imaging.

PMID- 15853715
TI  - Post-assembly peptide modifications by chemical methods.
AB  - The demand for peptide drugs is increasing and in this context, "post-assembly
      (or post-translational) peptide modification strategies" by chemical manipulation
      of intact oligo-peptides has provided several analogues. Compounds prepared by
      this method are useful therapeutic molecules for structure activity studies.
      Herein, we describe various chemical methods such as cross-coupling reactions,
      cycloaddition reactions, radical reactions and ring-closing metathesis reactions
      that are useful for post-translational peptide modifications.

PMID- 15853716
TI  - 2(3H)-benzoxazolone and bioisosters as "privileged scaffold" in the design of
      pharmacological probes.
AB  - The 2(3H)-benzoxazolone heterocycle and its bioisosteric surrogates (such as
      2(3H)-benzothiazolinone, benzoxazinone, etc.) have received considerable
      attention from the medicinal chemists owing to their capacity to mimic a phenol
      or a catechol moiety in a metabolically stable template. These heterocycles and
      pyrocatechol have indeed similar pKa's, electronic charge distribution, and
      chemical reactivity. Therapeutic applications of this template are very broad,
      and range from analgesic anti-inflammatory compounds (including PPAR-gamma
      antagonists) to antipsychotic and neuroprotective anticonvulsant compounds. High
      affinity ligands have been obtained also for dopaminergic (D2 and D4),
      serotoninergic (5-HT1A and 5-HT-2A), sigma-1 and sigma-2 receptors. Owing to the
      high number of positive hits encountered with this heterocycle and its congeners,
      2(3H)-benzoxazolone template certainly deserves the title of "privileged
      scaffold" in medicinal chemistry.

PMID- 15853717
TI  - HIV vaccine rationale, design and testing.
AB  - A central obstacle to the design of a global HIV vaccine is viral diversity.
      Antigenic differences in envelope proteins result in distinct HIV serotypes,
      operationally defined such that antibodies raised against envelope molecules from
      one serotype will not bind envelope molecules from a different serotype. The
      existence of serotypes has presented a similar challenge to vaccine development
      against other pathogens. In such cases, antigenic diversity has been addressed by
      vaccine design. For example, the poliovirus vaccine includes three serotypes of
      poliovirus, and Pneumovax presents a cocktail of 23 pneumococcal variants to the
      immune system. It is likely that a successful vaccine for HIV must also comprise
      a cocktail of antigens. Here, data relevant to the development of cocktail
      vaccines, designed to harness diverse, envelope-specific B-cell and T-cell
      responses, are reviewed.

PMID- 15853718
TI  - Viral correlates of HIV-1 disease.
AB  - The transmission of HIV and the progression of HIV disease are influenced not
      only by a large number of human host factors, but also by certain correlates of
      the ever fluctuating virus quasispecies. The present review article aims at
      providing the current state of knowledge as well as an in-depth critical
      discussion of recent developments on the potential effects of HIV subtype,
      phenotype and attenuation on HIV disease. Despite the extensive research, several
      questions regarding the precise role that each of these correlates plays in human
      AIDS pathogenesis remain unanswered. Unraveling these roles is expected to aid
      the continued quest for truly effective antiretroviral drug regimens and
      preventive vaccines.

PMID- 15853719
TI  - Inpatient care of the HIV infected patient in the highly active antiretroviral
      therapy (HAART) era.
AB  - The inpatient presentation of the HIV infected patient has changed over the
      years. From the early years when patients presented with accumulating
      opportunistic infections that led to an early demise to the HAART era with
      reports of dramatic decreases in opportunistic infections and improvements in
      life expectancy, the evolution of inpatient HIV care has been a challenge to the
      clinician. In the HAART era the presentation of the HIV inpatient has diversified
      and in many ways is more challenging than the management of the HIV inpatient in
      the pre-HAART era. We will discuss the changing dynamics of HIV inpatient care
      from socioeconomic changes to changes in the presentation and reasons for
      hospitalization.

PMID- 15853720
TI  - Structural bases of the annealing of primer tRNA(3Lys) to the HIV-1 viral RNA.
AB  - To promote the initiation of reverse transcription, the HIV-1 virus uses a host
      tRNA as a primer, tRNA(3Lys). The annealing of tRNA(3Lys) to the viral RNA
      requires the breaking of the 3D structure of the tRNA and RNA rearrangements, to
      form a stable initiation complex recognised by the reverse transcriptase. The
      annealing is mediated by a viral factor, the nucleocapsid protein. This protein
      has been studied for a long while to define the role of its different sub-domains
      and their mode of action. Only recently, a consensus view seems to emerge. The
      structure of the initiation complex, is still discussed. The goal of this review
      is to clarify what is known about the formation and the structure of the
      tRNA/viral RNA complex and the role of the nucleocapsid protein from a structural
      point of view.

PMID- 15853721
TI  - Non-replicating viral vector-based AIDS vaccines: interplay between viral vectors
      and the immune system.
AB  - During the past 20 years, the development of HIV vaccines has come a long way.
      The focus has progressively changed from the traditional protein-based HIV
      vaccines that induce humoral immunity to the live recombinant viral vector-based
      HIV vaccines capable of eliciting both cellular and humoral immune responses.
      These new viral vector-based vaccines encoding multiple HIV antigens, delivered
      either alone or in heterologous prime-boost modalities elicited antigen-specific
      CTL responses in immunized hosts and protected animals from disease. The viral
      vector-based vaccines have proven to be potent vaccines in pre-clinical studies
      and foster the hope to put an end to the ever-increasing threat of the AIDS
      epidemic. Several unique features of viral vector-based HIV vaccines have
      contributed to their success, including their intrinsic immune-modulating
      properties, high transduction efficiency, and in vivo production of immunogens
      within the cell mimicking a natural infection without the associated health
      risks. In this review, we will discuss the characteristics of non-replicating
      viral vectors most commonly used for HIV vaccines with a particular focus on
      immune responses elicited by the vector particles alone and their effect on the
      potency of viral vector-based HIV vaccines.

PMID- 15853722
TI  - Evaluation of a low cost reverse transcriptase assay for plasma HIV-1 viral load
      monitoring.
AB  - We evaluated a low cost manual reverse transcriptase assay (ExaVir Load V.1 and
      V.2; Cavidi Tech AB) against commercially available HIV RNA assays that quantify
      viral load to assess its suitability for use in resource-constrained settings.
      Frozen plasma samples previously tested for RNA by RT-PCR (Roche Diagnostics) and
      bDNA (Bayer Diagnostics) were retested for RT activity. Text sequence obtained
      from HIV genotype analysis was submitted to the Stanford HIV Resistance Database
      V.3.9 and were examined for resistant virus. Detectable RT was present in 98% of
      samples (V.1; n=127) and in 95% of samples (V.2; n=69) with RNA >10,000 and
      >1,000 copies/ml respectively. Positive association was found between the log10
      RNA copies/ml and log10 RT copies/ml equivalents variables using Pearson's
      correlation (V.1: r=0.89, n=189; V.2: r=0.89, n=85). The RT activity over time
      closely followed the trend for RNA levels in samples from 10 HIV seropositive
      patients with progressive disease. A strong association between RT and RNA was
      also found with paired samples from 19 patients taken at initiation or change of
      antiretroviral therapy and again within 2 months. Current (n=40) or no (n=119)
      exposure to efavirenz therapy had no effect on RT assay performance despite
      efavirenz binding tightly to the RT enzyme. Samples that demonstrated resistance
      to the non-nucleoside RT inhibitors (n=112) had a decrease in RT of 0.20 log10
      indicating a possible decrease in RT fitness. The RT assay showed good
      association with current molecular assays, and V.2 is sufficiently sensitive for
      monitoring HIV viral load in resource-constrained settings.

PMID- 15853724
TI  - What they are, how they work and why they do what they do? The story of SV40
      derived gene therapy vectors and what they have to offer.
AB  - The natural function of viruses is to deliver their genetic material to cells.
      Among the most effective of viruses in doing that is Simian Virus-40 (SV40). The
      properties that make SV40 a successful virus make it an attractive candidate for
      use as a gene delivery vehicle: high titer replication, infectivity for almost
      all nucleated cell types whether the cells are dividing or resting, potential for
      integration into cellular DNA, a peculiar pathway for entering cells that
      bypasses the cells' antigen processing apparatus, very high stability, and the
      apparent ability to activate expression of its own capsid genes in trans.
      Exploiting these and other characteristics of wild type (wt) SV40, increasing
      numbers of laboratories are studying recombinant (r) SV40-derived vectors. Among
      the uses to which these vectors have been applied are: delivering therapy to
      inhibit HIV, hepatitis C virus (HCV) and other viruses; correction of inherited
      hepatic and other protein deficiencies; immunizing against lentiviral and other
      antigens; treatment of inherited and acquired diseases of the central nervous
      system; protecting the lung and other organs from free radical-induced injury;
      and many others. The effectiveness of these vectors is a reflection of the
      adaptive evolution that produced their parent virus, wt SV40. This article
      explores how and why these vectors work, their strengths and their limitations,
      and provides a functional model for their exploitation for experimental and
      clinical applications.

PMID- 15853723
TI  - C3d enhances immune responses using low doses of DNA expressing the HIV-1
      envelope from codon-optimized gene sequences.
AB  - DNA vaccinations effectively induce both humoral and cellular immune responses to
      immunogens from diverse infectious agents. However, DNA vaccines expressing the
      HIV-1 envelope glycoprotein (Env) are poorly immunogenic when expressed from wild
      type (wt) DNA sequences. Two recent approaches used to enhance the immunogenicity
      of Env expressed from a DNA vaccine are the fusion of the molecular adjuvant,
      C3d, to a soluble form of Env and the use of codon-optimized (co) env gene
      inserts. Independently, each approach enhances antibody titer and cellular
      responses against Env expressed from gene inserts. The goal of this study was to
      examine if both codon-optimization of env gene inserts and C3d conjugation to Env
      could function in a synergistic manner to enhance immunogenicity. Mice (BALB/c)
      were inoculated with decreasing doses (2.0 microg, 0.2 microg or 0.02 microg) of
      co DNA expressing Env alone or fused to three copies of murine C3d (mC3d3) gene.
      Mice vaccinated with the highest dose (2.0 microg) of DNA had high anti-Env
      specific antibody titers regardless of the addition of mC3d3. At lower doses (0.2
      microg and 0.02 microg) of DNA, mice vaccinated with Env-mC3d3 had enhanced
      immune responses compared to mice vaccinated with DNA expressing Env only. In
      addition, mice vaccinated with Env-mC3d3 at the highest doses of DNA had enhanced
      interleukin-4 secreting cells, while mice vaccinated with the lowest dose of DNA
      had enhanced interferon-gamma secreting cells. Therefore, both codon-optimization
      of env sequences and C3d conjugation to Env appear to enhance anti-Env antibodies
      in an independent and additive manner.

PMID- 15853725
TI  - Gene therapy for bone regeneration.
AB  - Efficacious bone regeneration could revolutionize the clinical management of many
      bone and musculoskeletal disorders. Bone has the unique ability to regenerate and
      continuously remodel itself throughout life. However, clinical situations arise
      when bone is unable to heal itself, as with segmental bone loss, fracture non
      union, and failed spinal fusion. This leads to significant morbidity and
      mortality. Current attempts at improved bone healing have been met with limited
      success, fueling the development of improved techniques. Gene therapy in many
      ways represents an ideal approach for augmenting bone regeneration. Gene therapy
      allows specific gene products to be delivered to a precise anatomic location. In
      addition, the level of transgene expression as well as the duration of expression
      can be regulated with current techniques. For bone regeneration, the gene of
      interest should be delivered to the fracture site, expressed at appropriate
      levels, and then deactivated once the fracture has healed. Delivery of biological
      factors, mostly bone morphogenetic proteins (BMPs), has yielded promising results
      both in animal and clinical studies. There has also been tremendous work on
      discovering new growth factors and exploring previously defined ones. Finally,
      significant advances are being made in the delivery systems of the genes, ranging
      from viral and non-viral vectors to tissue engineering scaffolds. Despite some
      public hesitation to gene therapy, its use has great potential to expand our
      ability to treat a variety of human bone and musculoskeletal disorders. It is
      conceivable that in the near future gene therapy can be utilized to induce bone
      formation in virtually any region of the body in a minimally invasive manner. As
      bone biology and gene therapy research progresses, the goal of successful human
      gene transfer for augmentation of bone regeneration draws nearer.

PMID- 15853726
TI  - Non-viral gene delivery to the lungs.
AB  - The lung represents an important target for gene therapy: for correction of
      genetic abnormalities such as cystic fibrosis, for lung cancer therapy, and for
      vaccination. Genes in the form of expression plasmids can be delivered both by
      the intravenous route and via the airways. So-called "naked" DNA can be delivered
      by both of these methods, but gene expression is low. Successful delivery is
      usually accomplished by complexing the DNA with cationic lipids or with
      polycations. This review will discuss the efficacy of delivery for particular
      purposes by various methods and complexing agents, as well as issues of
      biodistribution, inflammatory reactions, and improvements in formulations. Non
      viral gene delivery to the lung has a long history of development, and it is now
      poised to represent a significant addition to the medical arsenal.

PMID- 15853727
TI  - Gene therapy in in vivo isolated perfusion models.
AB  - Locoregional administration of a genetic construct by means of in vivo, in situ
      isolated perfusion (IP) of a target organ or extremity is a method that may
      increase in vivo efficacy. Vascular isolation and perfusion minimizes systemic
      exposure and thereby reduces unwanted side effects. Isolated hepatic perfusion
      (IHP) is the most extensively studied IP model, especially in gene therapy
      protocols for inborn errors of metabolism. To achieve stable transduction most
      frequently retroviruses are used in IHP. IHP is combined with hepatectomy or
      vascular ligation of liver lobes to induce liver regeneration increasing
      transduction efficacy. When adenoviruses are used in IHP high transduction
      percentages of hepatocytes can be achieved without significant toxicity. In tumor
      models adenoviral IHP has been performed, but has not been very successful up
      till now. Isolated limb perfusion (ILP) is a promising treatment modality in pre
      clinical cancer gene therapy studies. After ILP a homogeneous distribution of
      transduced cells was demonstrated especially at the viable rim of the tumor and
      around tumor associated vessels. Moreover complete tumor responses have been
      observed. Isolated pulmonary perfusion (IPP) results in selective expression in
      the perfused lung and the duration of expression is longer than after systemic
      administration. In rats a significant decrease of tumor nodules upon IPP can be
      achieved. Furthermore other less studied perfusion models are discussed: isolated
      kidney perfusion (IKP), isolated spleen perfusion (ISP) and isolated cardiac
      perfusion (ICP). IP is a methodology that delivers vectors highly selectively,
      with a long exposure time and high concentrations at the target side. This
      results in higher transduction rates and thereby may improve therapeutic effects.

PMID- 15853728
TI  - Adenoviral gene delivery for HIV-1 vaccination.
AB  - The AIDS epidemic continues to spread throughout nations of Africa and Asia and
      is by now threatening to undermine the already frail infrastructure of developing
      countries in Sub-Saharan Africa that are hit the hardest. The only option to stem
      this epidemic is through inexpensive and efficacious vaccines that prevent or at
      least blunt HIV-1 infections. Despite decades of pre-clinical and clinical
      research such vaccines remain elusive. Most anti-viral vaccines act by inducing
      protective levels of virus-neutralizing antibodies. The envelope protein of HIV
      1, the sole target of neutralizing antibodies, is constantly changing due to
      mutations, B cell epitopes are masked by heavy glycosylation and the protein's
      structural unfolding upon binding to its CD4 receptor and chemokine co-receptors.
      Efforts to induce broadly cross-reactive virus-neutralizing antibodies able to
      induce sterilizing or near sterilizing immunity to HIV-1 have thus failed.
      Studies have indicated that cell-mediated immune responses and in particular CD8+
      T cell responses to internal viral proteins may control HIV-1 infections without
      necessarily preventing them. Adenoviral vectors expressing antigens of HIV-1 are
      eminently suited to stimulate potent CD8+ T cell responses against transgene
      products, such as antigens of HIV-1. They performed well in pre-clinical studies
      in rodents and nonhuman primates and are currently in human clinical trials. This
      review summarizes the published literature on adenoviral vectors as vaccine
      carriers for HIV-1 and discusses advantages and disadvantages of this vaccine
      modality.

PMID- 15853729
TI  - Cancer gene therapy utilizing interleukin-13 receptor alpha2 chain.
AB  - Cancer cells are known to express cell surface molecules such as specific
      antigens or cytokine receptors, e.g., EGFR, Fas/CD95, gp100, HER-2/neu, IL
      13Ralpha2, and MAGE. Among them, interleukin-13 receptor (IL-13R) alpha2 chain is
      expressed on certain types of cancer cells including glioblastoma, AIDS Kaposi's
      sarcoma, and head and neck cancer. This protein is one of the receptor components
      for IL-13, a Th2 cell-derived pleiotropic immune regulatory cytokine. IL
      13Ralpha2 chain on these cancer cells can be targeted with a receptor-directed
      cytotoxin termed IL13-PE to induce specific cancer cell killing, however, this
      molecule does not mediate cytotoxicity to cells that do not express or express
      low levels of IL-13Ralpha2. In order to achieve a broad therapeutic window for
      IL13-PE, plasmid-mediated gene transfer of IL-13Ralpha2 in cancer cells was
      employed in vitro and in vivo. Cancer cells transfected with IL-13Ralpha2
      demonstrated increased binding to IL-13 and sensitivity to IL13-PE in vitro. In
      vivo intratumoral gene transfer of IL-13Ralpha2 profoundly enhanced the antitumor
      activity of IL13-PE, providing complete elimination of established tumor in some
      xenografts. In this review article, current findings from IL-13Ralpha2 gene
      transfer in a variety of human cancer models in nude mice are summarized. In
      addition, safety issues and possible future directions utilizing this therapeutic
      approach are discussed.

PMID- 15853730
TI  - DNA repair proteins as molecular therapeutics for oxidative and alkylating lung
      injury.
AB  - Endogenous and environmental oxidation is increasingly becoming an important
      factor associated with numerous disorders in both children and adults. The lung
      is particularly prone to oxidation, as the gas exchange organ is continuously
      exposed to a great deal of airborne oxidants. Lung oxidation-induced toxicity is
      a critical clinical problem that is currently lacking cure. For example,
      treatment for acute respiratory distress syndrome (ARDS), a common type of acute
      diffuse lung injury, is strictly supportive. Alkylating chemotherapeutics and
      many methyl chemicals can cause acute or chronic lung injury, which is also
      difficult to treat. Many new approaches are being tried to improve the treatment
      of lung oxidation and alkylation; one of these is the use of DNA repair proteins,
      such as base excision repair proteins that are largely involved in repairing DNA
      damage caused by oxidation and alkylation. Recent advances have revealed their
      promising potential for treating oxidation toxicity. Here we discuss discoveries
      that have led to this possibility, including pioneering research into the
      cellular signaling transduction and molecular mechanisms of DNA repair proteins.
      In conclusion, when combined with other therapeutic measures such as anti-oxidant
      chemicals and enzymes, DNA repair proteins may have great potential for treating
      acute and chronic lung toxicity induced by oxidation and alkylation.

PMID- 15853731
TI  - Adenovirus-mediated transgene-engineered dendritic cell vaccine of cancer.
AB  - Dendritic cells (DCs) are the most effective antigen presenting cells (APCs) to
      elicit both primary and secondary T-cell response that is critical for antitumor
      immunity and elimination of intracellular pathogens. Therefore, DCs pulsed ex
      vivo with antigens have the potential used as cell-based vaccines against tumors.
      Viral vectors derived from adenoviruses have been extensively used to pulse DCs
      ex vivo by delivering genes encoding immunomodulatory molecules and tumor
      antigens to DCs since these vectors are relatively safe, effective in inducing
      the maturation of DCs, and can accommodate large expression cassettes encoding
      antigens. One of the hurdles for gene delivery to DCs by adenovirus (Ad) vectors,
      however, is low transfection efficiency of DCs due to the paucity of Ad receptor
      on DCs. To overcome this obstacle, targeted Ad vectors have been made by
      modifying viral capsid proteins. These targeted Ad vectors not only enhance the
      gene delivery to DCs, but also allow in vivo gene delivery to DCs, thus avoiding
      ex vivo manipulation of DCs.

PMID- 15853732
TI  - Approaches for the cure of type 1 diabetes by cellular and gene therapy.
AB  - Type 1 diabetes results from insulin deficiency caused by autoimmune destruction
      of insulin-producing pancreatic beta cells. Islet transplantation, beta cell
      regeneration, and insulin gene therapy have been explored in an attempt to cure
      type 1 diabetes. Major progress on islet transplantation includes substantial
      improvements in islet isolation technology to obtain viable and functionally
      intact islets and less toxic immunosuppressive drug regimes to prevent islet
      graft failure. However, the availability of human islets from cadaveric pancreata
      is limited. Regeneration of pancreatic beta cells from embryonic or adult stem
      cells may overcome the limited source of islets and transplant rejection if beta
      cells are regenerated from endogenous stem cells. However, it is difficult to
      overcome the persisting hostile beta cell-specific autoimmune response that may
      destroy the regenerated beta cells. Insulin gene therapy might overcome the
      weakness of islet transplantation and beta cell regeneration with respect to
      their vulnerability to autoimmune attack. This method replaces the function of
      beta cells by introducing various components of the insulin synthetic and
      secretory machinery into non- beta cells, which are not targets of beta cell
      specific autoimmune responses. However, there is no regulatory system that
      results in the expression and release of insulin in response to glucose with
      satisfactory kinetics. Although there is no perfect solution for the cure of type
      1 diabetes at the present time, research on a variety of potential approaches
      will offer the best choices for the cure of human type 1 diabetes.

PMID- 15853734
TI  - NOS:molecular mechanisms, clinical aspects, therapeutic and monitoring
      approaches.
AB  - Nitrosative stress and nitration of proteins in airway epithelium maybe
      responsible for steroid resistance in asthma and steroid ineffectiveness in
      chronic obstructive pulmonary disease (COPD), supporting the potential role of
      future therapeutic strategies aimed at regulating NO synthesis in asthma and COPD
      (for example, combination treatment with NOS inhibitors and corticosteroids).
      Here, the potential role of NO modulators (NO synthase inhibitors and NO donors)
      has been reviewed, which if are given on a regular basis may have clinical
      benefit in asthma and COPD.

PMID- 15853735
TI  - Arachidonic acid signaling in pathogenesis of allergy: therapeutic implications.
AB  - In recent years, significant progress has been made in understanding the
      involvement of pro-inflammatory lipidic mediators in the pathogenesis of allergic
      diseases. The most relevant lipidic mediator is arachidonic acid and its
      metabolites. Arachidonic acid is the precursor for biosynthesis of eicosanoids,
      potent mediators of inflammation that have been implicated in the pathogenesis of
      diverse disease processes. Eicosanoids are mainly synthesized by the action of
      cyclo-oxygenase (prostaglandin endoperoxide synthase) that generates
      prostaglandins and thromboxane, and 5-lipoxygenase, which leads to the production
      of leukotrienes. In addition, 12- and 15-lipoxygenase are found in mammalian
      systems. The activity of these enzymes results in the formation of different
      hydroxyeicosatetraenoic acids, but their functions in vivo have not been clearly
      established in normal or pathological states. Since several arachidonic acid
      metabolites clearly play an important role in allergic response, a substantial
      effort has been directed to understanding the cellular and molecular aspects of
      these pathways and their pharmacological modulation. This review summarizes some
      of these aspects based on our current knowledge of the involvement of arachidonic
      metabolism in the pathogenesis of allergic diseases and outlines the potential
      therapeutic opportunities that can result from the modulation of these
      metabolites.

PMID- 15853736
TI  - The role of beta(2)-adrenergic receptors in inflammation and allergy.
AB  - Essential role of beta(2)-adrenoreceptor (beta(2)AR) in airway relaxation is well
      established. Nevertheless, beta(2)AR seems playing an actual role in allergy and
      inflammation. Interaction between beta(2)AR and proinflamatory cytokines in
      airway smooth muscle has been revealed. Being located on proinflamatory cells,
      beta(2)ARs may influence function of these cells in vivo. It was clear
      established, that stimulation of beta(2)AR inhibits release of proinflamatory
      mediators from mast cells, influences T-cell growth and function, eosinophil
      survival and function, including GM-CSF- or PAF-induced degranulation.
      Stimulation of beta(2)ARs, located on alveolar macrophages and epithelial cells,
      has ambiguity influence on their regulation and function, including phagocytosis
      and mediator secretion, in vivo. Vascular responses, resulting in inhibition of
      plasma exudation were confirmed, but modulation of sensory nerves via beta(2)AR
      is not certain yet. beta(2)AR-agonists are effective in treatment of immediate
      allergic reactions, but desensitisation of beta(2)ARs on inflammatory cells may
      result in paradoxical effects, especially in asthma. In summary, it is clear that
      beta(2)ARs may play an anti-inflammatory role in vitro. Unfortunately, in vitro
      data have shown limited applicability in vivo; therefore further research in this
      field is required.

PMID- 15853737
TI  - Targeting chemoattractant receptors in allergic inflammation.
AB  - Asthma, atopic dermatitis, allergic rhinitis, which are amongst the most
      clinically relevant allergic disorders in industrialized countries affecting
      hundreds of millions of people world-wide, are characterized by tissue
      infiltration of Th2 cells, eosinophils, mast cells and basophils. Recruitment of
      these leukocyte subpopulations proceeds in response to specific chemotactic clues
      produced by tissue resident cells and is further amplified by incoming
      leukocytes. Over the last decade a number of receptors for chemokines and other
      chemoattractants have been identified on distinct leukocyte subpopulations
      participating to the pathogenesis of allergic inflammation. Preferential
      expression of discrete chemoattractant receptors on relevant cell types and their
      up-regulation in affected organs and animal models of allergic inflammation has
      helped to restrict the list of culprits. Although searching of the appropriate
      target for pharmacological intervention is still in progress, discrete
      chemoattractant receptors are already attracting a strong interest from the
      pharmaceutical industry. Here, we will review the most recent advances on the
      role that specific chemoattractant receptors play in the pathogenesis of allergic
      inflammation and will discuss emerging developments in this field.

PMID- 15853738
TI  - CD14 and toll-like receptors: potential contribution of genetic factors and
      mechanisms to inflammation and allergy.
AB  - Innate and adaptive immune responses evolve as protective mechanisms against
      infectious microorganisms in humans. CD14 and toll-like receptors (TLRs) are
      examples of pattern recognition receptors that detect antigenic molecules on the
      surface of gram-positive (peptidoglycans, lipoteichoic acid) and gram-negative
      (lipopolysaccharide) bacteria. In vitro studies suggest that lipopolysaccharide
      is a potent inducer of interleukin-12 production that is mediated by both CD14
      and TLR4. The associated increase in interferon-gamma steers our immune system
      away form the allergy-driven type-2 helper T cell phenotype. Epidemiological
      studies that shed light on the possible protective influences of natural
      microbial exposure on asthma and atopy development will be discussed. Recent
      insights into the complex mechanisms of human innate immunity suggest that
      genetic variability in genes encoding its components may alter the susceptibility
      to develop atopic disorders and other complex human diseases. The findings of
      these genetic association studies will be presented. Although highly conserved
      across a wide range of species, innate immunity genes demonstrate considerable
      inter-ethnic variability predominantly in the form of single nucleotide
      polymorphisms. The frequencies of these polymorphisms in CD14 and TLR genes in
      different ethnic groups will be discussed. Genetic variation in these genes may
      also play a role in the development of other human diseases that have an
      inflammatory component. Lastly, the prospect of using immunomodulatory agents
      targeting on the innate immunity to treat or even prevent asthma and other
      allergic diseases will be discussed.

PMID- 15853739
TI  - Matrix metalloproteinase-9 and airway remodeling in asthma.
AB  - Airway remodeling is a major change responsible for irreversible asthmatic
      airflow restriction. The Th-2 cytokines-dominant eosinophilic inflammatory
      mechanism cannot fully explain the progressive subepithelial fibrosis and
      structural changes in the extracellular matrix (ECM). Matrix metalloproteinases
      (MMPs) are the key enzymes responsible for ECM degradation. MMPs are normally
      produced and secreted under the tight regulation of, at least, 3 different
      levels: the gene transcriptional level, the activation of the latent form of
      enzyme, and the inactivation by specific endogenous inhibitors. In asthmatic
      condition, as shown by the large amount of accumulated evidence in this review,
      MMP-9 is the most relevant among the 23 kinds of human MMPs at present detected.
      Although the mechanism is still under investigation and not accurately known, the
      imbalance between MMP-9 and tissue inhibitor of metalloproteinase-1 is considered
      a major theory to explain the progression of asthmatic airway remodeling. Various
      inflammatory cytokines including TGF beta and growth factors play a pivotal role
      in MMP-9 production and secretion. This review mainly focuses upon the pivotal
      role of MMP-9 in airway remodeling, and also upon major cellular source of MMP-9
      in asthma such as eosinophils, neutrophils, epithelial cells and alveolar
      macrophages. This review also refers to the partial contribution of nitric oxide
      to MMP-9 in asthma.

PMID- 15853742
TI  - Modulation of TNF receptor family members to inhibit autoimmune disease.
AB  - Certain members of the TNF-receptor family have shown proinflammatory function
      during immune activation and can be directly involved with the pathogenic effects
      observed during an autoimmune episode. The TNF-R family members summarized in
      this review includes: TNF-RI + II, OX40, and 4-1BB and they are expressed on a
      variety of leukocytes within the body. Studies within the last decade suggest
      that all of these proteins or their natural ligands can be targeted with various
      agents designed to diminish clinical signs of disease in autoimmune models. The
      data from the preclinical models specifically involving TNF-blockade have led to
      the development of clinical trials for patients with multiple sclerosis and
      rheumatoid arthritis. This review will chronicle the preclinical development of
      agents designed to inhibit OX40 and 4-1BB functions in autoimmunity and discuss
      relevant preclinical and clinical data associated with TNF-blockade.

PMID- 15853743
TI  - Therapeutic blockade of TCR signal transduction and co-stimulation in autoimmune
      disease.
AB  - Autoimmune diseases are initiated and maintained by presentation of self antigen
      through complex interactions between different cells of the immune system. In
      most autoimmune disorders, autoantigen-specific responses are induced by the
      activation of specific T cells with self peptides displayed on activated antigen
      presenting cells (APCs). These T cells may then activate and drive B cell
      responses that either initiate or contribute to chronic disease pathogenesis. In
      order to activate the T cell, two signals are required: T cell receptor (TCR)
      engagement by autoantigen presented in the context of self MHC class II and
      costimulation (CD28-CD80/CD86 interactions). Feedback must also be provided to
      the APC through MHC class II engagement by the TCR and through costimulatory
      events controlling T cell differentiation and effector function (CD154-CD40
      interactions, among others). With this in mind, numerous strategies have been
      developed to block the engagement and activation of self-reactive cells. We
      review and discuss recent progress in understanding the efficacy and underlying
      molecular mechanisms of three separate immunotherapeutic strategies targeting the
      TCR and costimulatory molecules: i) blocking TCR signaling (using non-mitogenic
      anti-CD3 monoclonal antibody); ii) blocking CD28 costimulation (anti-B7
      monoclonal antibody blockade); and iii) blocking CD40 engagement on APCs (anti
      CD154 monoclonal antibody blockade).

PMID- 15853741
TI  - Systemic immunomodulation of autoimmune disease using MHC-derived recombinant TCR
      ligands.
AB  - Human autoimmune disease involves local activation of antigen-specific CD4(+) T
      cells that produce inflammatory Th1 cytokines leading to the further recruitment
      and activation of lymphocytes and monocytes, resulting ultimately in the
      destruction of target tissue. Antigen presenting cells (APCs) initiate activation
      of CD4(+) T cells in a multistep process that minimally involves co-ligation of
      the TCR and CD4 by the MHC class II/peptide complex and costimulation through
      additional T cell surface molecules such as CD28. Disruption of this highly
      orchestrated series of events can result in the direct modulation of CD4(+) T
      cell behavior. The interaction between MHC and TCR holds unique promise as a
      focal point for therapeutic intervention in the pathology of CD4(+) T cell
      mediated diseases, and MHC class II-derived Recombinant TCR Ligands ("RTLs") have
      emerged as a new class of therapeutics with potent clinical efficacy in a diverse
      set of animal models for multiple sclerosis. Here I review the systemic effect
      that RTL therapy has on the intact immune system and present an overview of a
      molecular mechanism by which RTL therapy could induce these systemic changes.

PMID- 15853744
TI  - TCR peptide vaccination in multiple sclerosis: boosting a deficient natural
      regulatory network that may involve TCR-specific CD4+CD25+ Treg cells.
AB  - Vaccination with self peptides contained within T cell receptor (TCR) chains,
      expressed by pathogenic Th1 cells can induce a second set of regulatory T cells
      that can reverse paralysis in rodents with experimental encephalomyelitis, and
      similarly, may have the potential to regulate myelin-reactive Th1 cells in
      patients with multiple sclerosis (MS). In this review, we discuss our recent
      discovery that TCR-reactive T cells generally possess classical inhibitory
      activity associated with Treg cells. CD4+CD25+ TCR-reactive T cells can inhibit
      CD4+CD25- indicator cells stimulated with anti-CD3/anti-CD28 antibody in a dose
      dependent and cell-contact-dependent manner. Additionally, CD4+CD25+ T cells from
      blood of healthy control donors have significant responses to a pool of
      discriminatory TCR peptides, including BV10S1P, BV19S20, BV13S7, BV12S2A2T,
      BV11S1A1T, BV21S3A1T, AV15S1, and BV12S1A1N1. Patients with MS have varying
      degrees of deficient responses to TCR peptides, and by association, a defect in
      Treg cell function as well. TCR peptide vaccination using a new tripeptide
      mixture emulsified in IFA produced strong T cell responses in 100% of MS
      recipients, a dramatic improvement over previous vaccines given i.d. in saline
      that induced TCR-reactive T cell responses in about 50% of recipients. Responders
      to vaccination had a tendency towards reduced MRI lesions, and an early
      indication of enhanced Treg activity mediated by TCR-reactive T cells that could
      provide suppression of target as well as bystander T cells. These data provide a
      strong foundation for future TCR vaccination studies that will critically test
      the ability of the tripeptide mixture to induce significantly enhanced Treg
      activity and possible clinical and MRI benefits in vivo.

PMID- 15853745
TI  - Evidence that pregnancy specific glycoproteins regulate T-Cell function and
      inflammatory autoimmune disease during pregnancy.
AB  - The capacity of the pregnancy state to regulate T-cell function is well
      documented. A consequence of this regulation is that many T-cell mediated
      autoimmune disorders, including multiple sclerosis (MS) are suppressed during
      pregnancy. The suppression of MS during pregnancy is more potent than the
      currently available treatments for this disease. Thus, the study of
      immunoregulatory factors of pregnancy could potentially result in the discovery
      of novel MS treatments. The regulation of T-cell function during pregnancy is
      likely the result of significant hormonal changes and may well involve
      immunoregulatory proteins derived from the placenta. Pregnancy specific
      glycoproteins (PSGs) are the most abundant placentally derived glycoproteins in
      the maternal serum. The levels of PSGs are highest during the third trimester of
      pregnancy, a time marked by the most profound suppression of MS disease attacks.
      Recent studies by our laboratories, and others, suggest that PSGs regulate T-cell
      function. We propose this regulation occurs by two distinct, but complementary
      mechanisms. PSGs may regulate T-cell function by (1) directly signaling
      tetraspanins present on the cell surface and by (2) regulating T-cell function
      indirectly through signaling of tetraspanins expressed by macrophages and
      dendritic cells. In this report, we will review evidence implicating PSGs as
      important immunoregulatory proteins and discuss our recent findings regarding the
      mechanisms by which PSGs regulate T-cell function.

PMID- 15853746
TI  - The role of CD8(+) T cells in multiple sclerosis and its animal models.
AB  - The role of CD8(+) T cells in multiple sclerosis (MS) and its animal models has
      been enigmatic. Most studies of MS have focused on the role of CD4(+) Th1 T cells
      and many therapeutic strategies have been directed toward ameliorating the
      activity of this subset. Some of these strategies were effective in experimental
      autoimmune encephalomyelitis (EAE), a widely used animal model for MS dependent
      on CD4(+) T cells, but paradoxically have worsened disease in MS patients. A
      great deal of evidence suggests that CD8(+) T cells contribute to the
      pathogenesis of MS and should be considered in designing therapies. CD8(+) T
      cells outnumber CD4(+) T cells in MS lesions, and both clonal expansion and
      enrichment of memory cells is preferentially seen in the CD8(+) T cell subset in
      the brain and cerebrospinal fluid of MS patients. New animal models have been
      developed that employ myelin-specific CD8(+) T cells to induce central nervous
      system autoimmunity. In a CD8(+) T cell model targeting myelin basic protein,
      clinical signs and pathology distinct from CD4(+) T cell-mediated disease were
      observed that exhibited similarities to some aspects of MS. These differences are
      consistent with distinct effector mechanisms employed by CD8(+) and CD4(+) T
      cells in mediating tissue damage and suggest a need to consider the activity of
      CD8(+) T cells in drug design. This review will focus on our current
      understanding of the role of CD8(+) T cells in MS and the new animal models that
      allow us to investigate further the pathogenicity of this subset.

PMID- 15853747
TI  - Mechanisms of cell signaling and inflammation in Alzheimer's disease.
AB  - Alzheimer's disease, the most common neurodegenerative dementia in the elderly,
      affects cognition, behavior and functioning, and a prominent neuroinflammatory
      component likely contributes to disease pathogenesis. The epidemiology of AD has
      previously shown that NSAID use decreases the incidence of AD, and evidence from
      tissue culture, in vivo models, and Alzheimer brain tissue studies indicate that
      inflammation in AD is mediated by the production of proinflammatory molecules,
      leading to microglial activation and neuronal damage. Preliminary clinical drug
      trials of anti-inflammatory agents, such as indomethacin, suggest slowing of
      cognitive decline in AD, further supporting a role for inflammation. The basic
      mechanisms underlying the AD neuroinflammatory cascade, which might accelerate
      the development of AD neuropathology, are poorly understood, but several recent
      studies implicate a number of established signaling pathways in this process.
      Microglial activation might involve beta-amyloid binding and activation of cell
      surface immune and adhesion molecules such as CD45, CD40, CD36 and integrins,
      with the subsequent recruitment of Src family tyrosine kinases such as Fyn, Lyn
      and Syk kinases. ERK and MAPK pathways are then activated, which induces
      proinflammatory gene expression and leads to the production of cytokines and
      chemokines. These molecules may then contribute to synaptic pruning, damage and
      loss, while TNFalpha can induce neuronal apoptosis and injury. The production of
      interleukins and other cytokines and chemokines also may lead to microglial
      activation, astrogliosis, and further secretion of proinflammatory molecules and
      amyloid, thus perpetuating the cascade. Simultaneously, direct neuronal injury
      from amyloid-induced signaling also contributes to neurodegeneration. Of clinical
      relevance, components of these pathways may be suitable targets for therapeutic
      modulation in AD and for the development of novel disease-modifying anti
      inflammatory therapy.

PMID- 15853748
TI  - Inflammatory mediators as potential therapeutic targets in the spine.
AB  - Inflammation plays a variable part in the pathogenesis of several spinal
      disorders. Ankylosing spondylitis is a chronic inflammatory arthropathy of the
      spine and rheumatoid arthritis, whilst affecting predominantly limb joints, also
      affects the cervical spine in a significant proportion of people. Inflammation is
      also involved in disorders such as disc herniation and sciatica, which have
      previously been thought of as being primarily mechanical or degenerative. Anti
      inflammatory agents which have been shown to be effective elsewhere in the body
      are discussed in this review as possible therapeutic agents in the spine. As the
      inflammatory cascade and immunopathology of these conditions continue to be
      elucidated, it has become apparent that individual molecules may be potential
      targets for inactivation or down-regulation. Candidates include pro-inflammatory
      cytokines, such as TNF-alpha, cytokines, e.g. IL-1 and IL-15, or enzymes
      enhancing the inflammation pathway such as the cyclooxygenases. Hence treatments
      based on inactivation of these molecules by various mechanisms, including
      antibodies, receptor antagonists, enzyme inhibitors or gene therapy, are being
      introduced. However, the mode of action of a particular molecule can be complex
      and sometimes apparently contradictory. For example, TNF-alpha is known to play
      an important role in promoting inflammation by upregulating expression of cell
      adhesion molecules on endothelial cells and stimulating the production of
      reactive oxygen intermediates, nitric oxide and prostaglandins. However, it can
      also have an immunosuppressive and anti-inflammatory role after prolonged
      release. Therefore, although inhibitors of many of these molecules are now in
      clinical application and trials (many with promising results in rheumatoid
      arthritis), it is important to remain vigilant and monitor long-term outcomes
      particularly when these treatments are used in clinical syndromes with relatively
      poorly defined immunopathology such as spinal disorders.

PMID- 15853749
TI  - TH2 cytokines and associated transcription factors as therapeutic targets in
      asthma.
AB  - The increasing levels of morbidity and mortality due to the rising prevalence of
      asthma and other allergic diseases have inspired investigations of several new
      molecular techniques to improve treatment. Recently, several preclinical studies
      have been published which utilize attributes or facets of DNA to address asthma
      therapy. These novel therapeutics include antisense oligonucleotides against TH2
      cytokines and associated transcription factors. While no clinical experience has
      yet been reported for any of these areas of research in asthma, specific small
      molecule inhibitors of TH2 cell responses would be desirable for treatment of
      this chronic disease. Six transcription factors (c-Maf, NF-AT, NF-IL-6, AP-1,
      STAT-6 and GATA-3) have been implicated in the differentiation of TH2-type
      lymphocytes and therefore, in addition to TH2-type cytokines, represent
      therapeutic targets for asthma. This review will focus on new research involving
      suppression of Th2-type cytokines and associated transcription factors using
      antisense and decoy oligonucleotides. Recently, novel oligonucleotides have been
      devised to improve stability in vitro and in vivo stability against nucleases,
      and the efficacy of these approaches will also be presented.

PMID- 15853750
TI  - Biological properties of baicalein in cardiovascular system.
AB  - The dried roots of Scutellaria baicalensis (S. baicalensis) Georgi (common name:
      Huangqin in China) have been widely employed for many centuries in traditional
      Chinese herbal medicine as popular antibacterial and antiviral agents. They are
      effective against staphylococci, cholera, dysentery, pneumococci and influenza
      virus. Baicalein, one of the major flavonoids contained in the dried roots,
      possesses a multitude of pharmacological activities. The glycoside of baicalein,
      baicalin is a potent anti-inflammatory and anti-tumor agent. This review
      describes the biological properties of baicalein (Table 1), which are associated
      with the prevention and treatment of cardiovascular diseases. Baicalein is a
      potent free radical scavenger and xanthine oxidase inhibitor, thus improving
      endothelial function and conferring cardiovascular protective actions against
      oxidative stress-induced cell injury. Baicalein lowers blood pressure in renin
      dependent hypertension and the in vivo hypotensive effect may be partly
      attributed to its inhibition of lipoxygenase, resulting in reduced biosynthesis
      and release of arachidonic acid-derived vasoconstrictor products. On the other
      hand, baicalein enhances vasoconstricting sensitivity to receptor-dependent
      agonists such as noradrenaline, phenylephrine, serotonin, U46619 and vasopressin
      in isolated rat arteries. The in vitro effect is likely caused by inhibition of
      an endothelial nitric oxide-dependent mechanism. The anti-thrombotic, anti
      proliferative and anti-mitogenic effects of the roots of S. baicalensis and
      baicalein are also reported. Baicalein inhibits thrombin-induced production of
      plasminogen activator inhibitor-1, and interleukin-1beta- and tumor necrosis
      factor-alpha-induced adhesion molecule expression in cultured human umbilical
      vein endothelial cells. The pharmacological findings have highlighted the
      therapeutic potentials of using plant-derived baicalein and its analogs for the
      treatment of arteriosclerosis and hypertension.

PMID- 15853751
TI  - Statins: effects beyond cholesterol lowering.

PMID- 15853752
TI  - Statins and thrombin.
AB  - L-Mevalonic acid is the distant precursor of cholesterol, in contrast to
      cholesterol, L-mevalonic acid, its distant precursor gives rise to farnesyl and
      geranylgeranyl pyrophosphates in relatively few metabolic steps. These isoprenyl
      pyrophophates covalently conjugate with specific G-proteins and serve as membrane
      anchors enabling them to carry out their function. Although farnesyl-proteins may
      participate in signal transduction, geranylgeranyl-proteins (e.g., Rho GTP
      binding proteins) are well known to downregulate signaling pathways by inhibiting
      L-mevalonic acid synthesis. Such inhibitors include 3-hydroxy-3-methylglutaryl
      CoA reductase inhibitors, drugs (statins) and isoprenoids of dietary origins,
      where Rho protein activation appears to be necessary for cellular-mediated
      thrombin generation. Thrombin and other proteases (e.g., coagulation factor Xa,
      tryptase) upregulate protease-activated receptor (PAR) synthesis and PAR
      activation promotes synthesis and expression of other proteins [e.g., tissue
      factor (TF) and plasminogen activator inhibitor-1 (PAI-1)]. With the PAR-1
      activating peptide SSFLRNP, we found that either cerivastatin or atorvastatin
      mitigated platelet stimulation in a time- and dose-dependent manner, as predicted
      if a statin-mediated Rho pathway is required. We also found that simvastatin
      decreased prothrombin fragments F1+2 in plasma from type 2 diabetics,
      demonstrating that statins downregulate thrombin generation. Thus, independent of
      cholesterol, statins and dietary isoprenoids behave as inhibitors of TF-dependent
      thrombin generation. Because thrombin has multiple physiological functions, the
      20 pleiotropic effects reported for statins may reflect a common mechanism for
      downregulation of thrombin-mediated events, in particular at the cellular level.

PMID- 15853753
TI  - Mechanisms for antiplatelet action of statins.
AB  - Hydroxymethyl-glutaryl coenzyme A reductase inhibitors (statins) offer important
      benefits for the large populations of individuals at high risk for coronary heart
      and cerebrovascular disease. the overall clinical benefits observed with statin
      therapy appear to be greater than what might be expected from changes in lipid
      profile alone, suggesting that the beneficial effects of such drugs may extend
      beyond their effects on serum cholesterol. Platelet hyperactivity is a key step
      in atherothrombosis and experimental data suggest that statins could exert an
      antiplatelet effect which could be involved in their protective action. In the
      present review we report of the major studies in humans showing the effect of
      statins on platelets, especially by the more sensitive methods to explore
      platelet function such as cytofluorymetric detection of specific proteins.
      Moreover we describe the putative mechanisms involved in platelet deactivation
      with particular regard to the effects related to cholesterol reduction or beyond
      lipid-lowering. Indeed, data from several studies suggest some differences among
      compounds in terms of timing of action by modulation of several activating
      pathways which could take part either in the early, cholesterol-lowering
      independent, effects in the acute phase of vascular disease or during chronic
      treatment.

PMID- 15853754
TI  - Cholesterol-independent effects of statins in inflammation, immunomodulation and
      atherosclerosis.
AB  - Atherosclerosis and its complications still represent the major cause of death in
      developed countries. Statins have revolutionized the treatment of dyslipidemia
      and demonstrated their ability to reduce and prevent coronary morbidity and
      mortality. Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase, an enzyme crucial to cholesterol synthesis. The effectiveness and
      rapidity of statin-induced decreases in coronary events led to the speculation
      that statins possess cholesterol-independent effects. Since mevalonate produced
      by the HMG-CoA reductase is not only the precursor of cholesterol, but also of
      non steroidal isoprenoid compounds, such as the farnesyl pyrophosphate and the
      geranylgeranyl pyrophosphate, statins also regulate the small signaling proteins,
      Ras and Rho. Thus, inhibition of these prenylated proteins might account for the
      non-lipid lowering effects of statins. In this review, we describe the numerous
      beneficial pleiotropic effects of statins that could modulate atherogenesis.

PMID- 15853755
TI  - Statin-induced vascular smooth muscle cell apoptosis: a possible role in the
      prevention of restenosis?
AB  - Growing evidence suggests that statins are more than simple lipid-lowering drugs.
      The so called pleiotropic effects of statins include multiple actions on cells of
      the vasculature. A large number of studies have confirmed that these compounds
      exert beneficial effects by mechanisms unrelated to cholesterol metabolism. For
      example, statins have been shown to inhibit the migration and proliferation of
      vascular smooth muscle cells (VSMC), and to induce apoptosis in this cell type.
      It is not yet clear if the induction of apoptosis in VSMC by statins is
      beneficial or detrimental. In the context of post-angioplasty restenosis,
      recurrent plaque growth after intervention, the inhibition of neointimal
      proliferation as well as a reduction of neointimal cell numbers by apoptosis is
      appealing. Multiple animal studies and clinical trials have therefore been
      undertaken to investigate effects of statin treatment on the development of
      restenosis, with very controversial results. Conversely, in advanced
      atherosclerotic lesions VSMC in the intima may stabilize the plaque and prevent
      plaque rupture by synthesizing collagen. VSMC in media adjacent to plaque areas
      or restenotic lesions should not be exposed to apoptosis promoting agents. In
      this context, recent evidence suggests that pravastatin protects such lesions by
      inhibiting inflammation and macrophage activation Our recent findings together
      with observations from other groups suggest that neointima cells are more
      sensitive to the induction of apoptosis than media VSMC. Importantly, statins
      were found to preferentially induce apoptosis in neointimal VSMC in our study.
      The purpose of the present review is to summarize statin effects on proliferation
      and apoptosis in VSMC in vitro and in vivo. Furthermore, the development of drug
      coated stents may help to deliver high local doses of statins to enhance their
      effectiveness in the treatment of post-angioplasty restenosis.

PMID- 15853756
TI  - Three's company: regulation of cell fate by statins.
AB  - Inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (statins), the rate
      limiting enzyme of the mevalonate biosynthetic pathway, are currently the leading
      prescription drugs worldwide. Programmed cell death (apoptosis) is a powerful
      physiological regulator of cellular development, function and dynamics. Statins
      are known to induce cellular apoptosis in vitro; however, the clinical relevance
      of this action remains controversial. This paper draws from 15 years' worth of
      research to explore the impact of statin treatment on cell fate, as represented
      by the interlinked processes of cellular growth, differentiation and apoptosis.
      In particular, I outline our current understanding of the pertinent molecular
      mechanisms; and discuss the evidence for clinical relevance of statin-induced
      apoptosis.

PMID- 15853757
TI  - The role of statins in oxidative stress and cardiovascular disease.
AB  - Statins have emerged as a highly efficacious class of drugs in the prevention of
      cardiovascular events. The primary mechanism of its cardioprotective effect is
      likely through its effectiveness in lowering serum lipids, particularly the low
      density lipoprotein (LDL) fractions. Recent studies suggest that statins also
      confer direct beneficial effects on the vascular cells in the attenuation of the
      atherogenic process through a variety of mechanisms. It remains the current dogma
      that oxidative modification of the LDL particles in the vessel wall plays a
      critical role for these lipoprotein particles to initiate the atherogenic
      cascade. The current failure of a number of antioxidants, which includes vitamin
      E, to favorably impact on the cardiovascular outcome in large scale clinical
      trials attests to the complexity of the oxidation processes in biological
      systems. In this review, we will highlight the current advances in a number of
      endogenous pro-oxidative and anti-oxidative systems in how they contribute to the
      net oxidative stress and how statin drugs may modulate this complex array of pro-
      and anti-oxidative processes.

PMID- 15853758
TI  - Common therapeutic strategies in the management of sexual dysfunction and
      cardiovascular disease.
AB  - Sexual dysfunction is a frequent complication of treated and untreated
      cardiovascular disease. In fact, approximately 30% of hypertensives have been
      found to suffer from erectile dysfunction (ED) resulting from arterial
      dysfunction. Recent evidence has suggested that ED may be an early indicator of
      subclinical cardiovascular disease. In women, the evidence is similar, but more
      limited, showing that in hypertensive patients there is an increased prevalence
      of sexual dysfunction involving decreased vaginal lubrication, decreased orgasm,
      and increased pain. Clouding the issue, however, is that some antihypertensive
      agents may induce sexual dysfunction in hypertensives with normal sexual
      function. In contrast to the chronic treatments used in hypertension, therapies
      for ED involve acute treatments (none currently approved for women) targeting
      vasodilation of penile arteries, resulting in erection. Common to the treatment
      of hypertension and ED is that the current therapies were not designed to target
      underlying disorders of local, neural, vascular, or endocrine origin. In fact,
      while blood pressure is lowered, and erectile responses are improved with the
      respective therapies, the causal abnormalities may progress thereby limiting the
      long-term effectiveness of the medication. Some antihypertensive agents have been
      shown to have additional effects beyond blood pressure reduction and their impact
      on sexual function is a key focus of this review. This review examines the
      current and future strategies for treatments of male and female sexual
      dysfunction and the potential for therapeutic modalities that go beyond the
      recovery of the responses by targeting the fundamental mechanisms common to both
      sexual dysfunction and cardiovascular disease.

PMID- 15853759
TI  - Effect of coenzyme Q10 on warfarin hydroxylation in rat and human liver
      microsomes.
AB  - Our previous animal study has suggested that the accelerated metabolism of
      warfarin enantiomers with concurrent coenzyme Q(10) (CoQ(10)) treatment accounts
      for the reduced anticoagulant effect of warfarin in rats. The present study was
      to assess the effect of CoQ(310) on individual hydroxylation pathways of the in
      vitro microsomal metabolism of warfarin enantiomers and to extrapolate in vitro
      data to in vivo situation. The effect of the antioxidant CoQ(10) on the
      hydroxylation of warfarin enantiomers was examined using rat and human liver
      microsomes. Based on the in vitro kinetic data, together with the information
      retrieved from the literature, the magnitude of warfarin-CoQ(10) interaction in
      man was quantitatively predicted. In rat liver microsomes, CoQ(10) exhibited a
      selective activation effect on the 4'-hydroxylation of S-warfarin, with a K(A)
      value (i.e. dissociation constant of the enzyme-activator complex) being one
      third and one fifth of those for the 6- and 7-hydroxylation, respectively. The
      activation effect of CoQ(10) was selective towards the 6- and 7-hydroxylation of
      R-warfarin at low substrate concentrations, but towards the 4'-hydoxylation of
      the R-enantiomer at high substrate concentrations. In human liver microsomes,
      CoQ(10) was a selective activator of the 7-hydroxylation of both R- and S
      enantiomers of warfarin, with K(A) values being half to one twelfth of those for
      the other pathways. A relatively accurate prediction was made for the increase in
      the total and hepatic clearance of both S- and R-warfarin in rats with concurrent
      CoQ(10) treatment based on their respective overall hydroxylation, when the
      active transport of CoQ(10)into the hepatocytes was taken into consideration. In
      man, one would expect about 32% and 17% increase in the total clearance of S- and
      R-warfarin, respectively, with coadministration of 100 mg CoQ(10). In both
      species, CoQ(10) had enzyme activation effect, which appeared to be
      regioselective but not stereoselective, on the formation of the phenolic
      metabolites of warfarin enantiomers. A moderate increase in the total clearance
      of warfarin enantiomers could occur with coadministration of CoQ(10)in humans.

PMID- 15853760
TI  - Quantitative in vivo microdialysis in pharmacokinetic studies: some reminders.
AB  - This paper reviews the empirical methods of quantitative microdialysis that have
      been used to interpret the results obtained from pharmacokinetic studies. The
      concept of extraction efficiency or recovery and the properties of recovery in
      vivo (variation with flow rate, time dependency and influence of the mode of
      administration) are considered. The most frequently used methods for determining
      recovery in vivo are described and evaluated in the light of recent theoretical
      studies. Specifically, we review the variation of flow rate method, the very slow
      flow method, the no net flux method and the delivery and retrodialysis methods.
      Special emphasis is placed on the description of each method, demonstrating its
      applicability to pharmacokinetic studies conducted under steady-state or
      transient conditions, and also its limitations. Finally, the more relevant
      studies that have compared the suitability of these methods are reviewed.

PMID- 15853761
TI  - Polymorphism of UDP-glucuronosyltransferase and drug metabolism.
AB  - UDP-glucuronosyltransferase is a group of catabolic enzymes involved in the
      detoxification and excretion of many xenobiotic and endogeneous substances in
      intrahepatic and extrahepatic tissues. The group consists of two subfamilies,
      UGT1 and UGT2. UGT1 consists of 5 exons and has a unique gene structure. There
      are thirteen exon 1s from UGT1A1 to UGT1A13P, and exon 2 to exon 5 are used in
      common for all mRNAs expressed from the gene. Each isoform of UGT1 results from
      differential splicing of exon1s to common exon 2-5, and has an unique spectrum of
      substrate specificity. In contrast, the genes of the UGT2 family consist of 6
      exons, and all the enzymes have an individual set of exon 1 to exon 6. In UGT1
      there are no reports of polymorphism in the common exons, although a number of
      polymorphisms have been reported for exon 1s. The mutations of UGT1A1 cause
      hereditary unconjugated hyperbilirubinemias: Crigler-Najjar syndrome type I, type
      II and Gilbert syndrome. UGT1A1 has two major polymorphisms--a missense mutation
      of G71R and an insertion mutation of TATA box. Prevalence of Gilbert syndrome is
      attributed to these polymorphisms. Since UGT1A1 metabolizes not only bilirubin
      but also hormones and drugs, the mutations could be involved in carcinogenesis
      and adverse drug reactions. Recent studies also revealed a widespread presence of
      diverse polymorphisms in other isoforms of UGT1 as well as the UGT2 family,
      including UGT1A6, UGTG1A7, UGT1A8, UGT1A10, UGT2B4, UGT2B7 and UGT2B15. The
      incidences and types of the polymorphisms for these enzymes are quite different
      in region and ethnic groups. Understanding of these polymorphisms is essential
      for the prevention of adverse effects of a considerable number of drugs and to
      predict cancer risks.

PMID- 15853762
TI  - Accelerated cytotoxicity mechanism screening using drug metabolising enzyme
      modulators.
AB  - By assessing how drug/new chemical entity (NCE) cytotoxicity is affected when
      their metabolic pathways are inhibited or activated, the metabolic pathways that
      activate versus detoxify drugs/NCEs can be identified. Reactive metabolites
      contributing to cytotoxicity can also be identified. In the following, the drug
      metabolizing enzyme inhibitors and activators used in vitro with freshly isolated
      rat hepatocytes for the accelerated cytotoxicity mechanism screening (ACMS) of
      drugs/NCEs (a technique used in our laboratory) are reviewed and, this technique
      is useful for determining in vivo rat hepatotoxicity mechanisms. The enzyme
      inhibitors/activators have been chosen on the basis of their selectivity,
      modulator effectiveness, and their lack of toxicity. The use of these
      inhibitors/activators with human hepatocytes or subcellular fractions for
      assessing human hepatotoxicity mechanisms is also reviewed.

PMID- 15853763
TI  - In vitro methods to study chemically-induced hepatotoxicity: a literature review.
AB  - Understanding the hepatotoxicity of drugs and chemicals is essential for progress
      in the pharmaceutical industry, medical science and academic research. The study
      of hepatotoxicity in vitro is complicated by the difficulty of maintaining
      hepatocytes in culture due to a lack of understanding of the humoral and matrix
      requirements of these cells. A variety of in vitro models of the liver have been
      developed, such as perfused livers, liver slices and three-dimensional perfused
      bioreactors, but the static cell culture is the most commonly used system. In
      this review we present the advantages and disadvantages of each system and their
      roles in the study of hepatotoxicity. We will also discuss how the various
      culture conditions such as medium and matrix composition affect the systems. The
      technological advances, which started the fields of genomics, proteomics and
      metabonomics are playing a very important role in uncovering novel biochemical
      pathways and markers of toxicity. Several of these studies have focused on
      hepatotoxicity, particularly on the effects of acetaminophen, carbon
      tetrachloride and aflatoxin B1. Finally, we will discuss the new field of systems
      biology, which focuses on interpreting and integrating data from all of the other
      fields.

PMID- 15853764
TI  - The GABA shunt: an attractive and potential therapeutic target in the treatment
      of epileptic disorders.
AB  - Epilepsy is the most common primary neurological disorder known. Epileptiform
      neurons undergo paroxysmal depolarization shifts (PDS), which result in the
      excessive sustained neuronal firing seen in epilepsy. These shifts are due to
      either an impairment of GABA mediated inhibition, or an enhancement of aspartate
      or glutamate mediated excitatory transmission. Recent research has focused on the
      cellular biology of seizures. 4-Aminobutyric acid (GABA) is a major inhibitory
      neurotransmitter of mammalian central nervous system. In neural and nonneural
      tissues, GABA is metabolized by three enzymes-glutamic acid decarboxylase (GAD),
      which produces GABA from glutamic acid, and the catabolic enzymes GABA
      transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH). Production
      of succinic acid by SSADH allows entry of the GABA carbon skeleton into the
      tricarboxylic acid cycle. GABA-T is present in a variety of circulating cells,
      including platelets and lymphocytes. SSADH, the final enzyme of GABA catabolism,
      has been detected in some of the tissues in which GAD and GABA-T have been
      identified. This paper is aimed at elucidating the organization of the GABA shunt
      and covers a review on the antiepileptic drugs, both established and currently
      under development targeted to the GABA shunt in order to bring about effective
      seizure control.

PMID- 15853765
TI  - A historical overview of the heterologous expression of mammalian UDP
      glucuronosyltransferase isoforms over the past twenty years.
AB  - UDP-Glucuronosyltransferases (UGTs) are actively involved in detoxification of
      xenobiotics and endogenous compounds and are a major source of drug inactivation
      and drug-drug interactions. UGTs are membrane-bound enzymes mostly localized in
      the endoplasmic reticulum (ER) and inner and outer nuclear membranes. UGT
      activities are totally dependent on the phospholipid content of the membrane and,
      as a result, are usually inactive when isolated from the ER in the presence of
      detergent. Several UGT expression systems have been described by different
      laboratories. They include expression in mammalian cells such as COS, V79 and
      HEK293. Also, baculovirus-infected insect cells systems have been developed and
      allow the expression of UGT isoforms with or without histidine molecule tags (His
      tags). Moreover, as for CYP450, UGT isoforms have been expressed in E.coli. This
      review concentrates on a detailed description of all these expression systems in
      terms of their use for substrate specificity studies and the preparation of pure
      UGT proteins for active site identification and other structural studies. The
      effect of detergents and alamethicin on UGT catalytic activity in different
      expression systems will be discussed. Moreover, extensive comparative studies on
      the characterization of recombinant UGTs in terms of substrate specificity,
      evaluation of kinetic parameters, and the effect of inhibitors will be presented
      in this review. An overall picture of the use of different UGT expression systems
      will help in selecting the best one for identification of the individual UGT
      isoforms involved in the glucuronidation of drugs, environmental pollutants and
      physiologically important endogenous compounds. Especially important is an
      expression system where UGTs are biosynthesized with His-tags. UGTs expressed in
      this system can be easily purified to homogeneity, which will result in
      significant development of structure-function relationship studies, including the
      identification of substrate active sites and eventual crystallization. These are
      underdeveloped areas of UGT research and the availability of these recombinant
      UGTs will allow these gaps to be filled.

PMID- 15853766
TI  - Age-associated decline in mitochondrial respiration and electron transport in
      Drosophila melanogaster.
AB  - The principal objective of the present study was to identify specific alterations
      in mitochondrial respiratory functions during the aging process. Respiration
      rates and the activities of electron transport chain complexes were measured at
      various ages in mitochondria isolated from thoraces of the fruit fly, Drosophila
      melanogaster, which consist primarily of flight muscles. The rates of state 3
      respiration (ADP-stimulated), RCRs (respiratory control ratios) and uncoupled
      respiration rates decreased significantly as a function of age, using either NAD+
      or FAD-linked substrates; however, there were no differences in state 4
      respiration (ADP-depleted) rates. There was also a significant age-related
      decline in the activity of cytochrome c oxidase (complex IV), but not of the
      other mitochondrial oxidoreductases examined. Exposure of mitochondria isolated
      from young flies to low doses of KCN or NaAz (sodium azide), complex IV
      inhibitors, decreased cytochrome c oxidase activity and increased the production
      of H2O2. Collectively, these results support the hypothesis that impairment of
      mitochondrial respiration may be a causal factor in the aging process, and that
      such impairment may result from and contribute to increased H2O2 production in
      vivo.

PMID- 15853768
TI  - Characterization of a recombinant type II 3-deoxy-D-arabino-heptulosonate-7
      phosphate synthase from Helicobacter pylori.
AB  - DAH7P (3-Deoxy-D-arabino-heptulosonate 7-phosphate) synthase catalyses the
      condensation reaction between phosphoenolpyruvate (PEP) and D-erythrose 4
      phosphate (E4P) as the first committed step in the biosynthesis of aromatic
      compounds in plants and micro-organisms. Previous work has identified two
      families of DAH7P synthases based on sequence similarity and molecular mass, with
      the majority of the mechanistic and structural studies being carried out on the
      type I paralogues from Escherichia coli. Whereas a number of organisms possess
      genes encoding both type I and type II DAH7P synthases, the pathogen Helicobacter
      pylori has only a single, type II, enzyme. Recombinant DAH7P synthase from H.
      pylori was partially solubilized by co-expression with chaperonins GroEL/GroES in
      E. coli, and purified to homogeneity. The enzyme reaction follows an ordered
      sequential mechanism with the following kinetic parameters: K(m) (PEP), 3 microM;
      K(m) (E4P), 6 microM; and kcat, 3.3 s(-1). The enzyme reaction involves
      interaction of the si face of PEP with the re face of E4P. H. pylori DAH7P
      synthase is not inhibited by phenylalanine, tyrosine, tryptophan or chorismate.
      EDTA inactivates the enzyme, and activity is restored by a range of bivalent
      metal ions, including (in order of decreasing effectiveness) Co2+, Mn2+, Ca2+,
      Mg2+, Cu2+ and Zn2+. Analysis of type II DAH7P synthase sequences reveals several
      highly conserved motifs, and comparison with the type I enzymes suggests that
      catalysis by these two enzyme types occurs on a similar active-site scaffold and
      that the two DAH7P synthase families may indeed be distantly related.

PMID- 15853769
TI  - Changes in the expression of genes related to bile acid synthesis and transport
      by the rat liver during hepatocarcinogenesis.
AB  - The relationship between BA (bile acid) secretion (measured by GC-MS) and the
      expression of genes (measured by reverse transcription real-time PCR) involved in
      liver BA transport and metabolism was investigated at 20 and 32 weeks during rat
      hepatocarcinogenesis. A progressive loss of mRNA for transporters (more marked
      for Ntcp, Bsep and Mrp2 than for Oatp1/Oatp1a1, Oatp2/Oatp1a4 and Oatp4/Oatp1b2)
      was found. The mRNA levels of Cyp7a1 and the nuclear receptors FXR (farnesoid X
      receptor), SHP (small heterodimer partner) and FTF (alpha-fetoprotein
      transcription factor) were not modified, whereas those of Cyp8b1 were enhanced
      and those of Cyp27 were reduced. Biliary secretion of CA (cholic acid) remained
      unchanged, whereas that of CDCA (chenodeoxycholic acid) and other non-C(12)
      hydroxylated BAs was diminished. The re-appearance of 'flat-BAs' (mainly allo-BAs
      at 20 weeks and Delta(4)-unsaturated-BAs at 32 weeks) probably reflects the
      progressive decrease observed in the expression of 3-oxo-Delta(4)-steroid 5beta
      reductase, together with the maintenance of steroid 5alpha-reductase type I. A
      significant correlation between the 5alpha-reductase/5beta-reductase ratio and
      bile output of 'flat-BAs' was found. In conclusion, during rat
      hepatocarcinogenesis, the expression of transporters/enzymes responsible for BA
      homoeostasis is changed due to mechanisms other than those controlled by
      FXR/SHP/FTF. These modifications result in the re-appearance of 'flat-BAs',
      together with an increased CA/CDCA ratio in bile.

PMID- 15853770
TI  - Paraoxonase-1 (PON-1) genotype and activity and in vivo oxidized plasma low
      density lipoprotein in Type II diabetes.
AB  - The HDL (high-density lipoprotein)-associated enzyme PON (paraoxonase)-1 protects
      LDL (low-density lipoprotein) from oxidative modification in vitro, although it
      is unknown if this anti-atherogenic action occurs in vivo. In a cross-sectional
      study of 58 Type II diabetic subjects and 50 controls, we examined the fasting
      plasma LDL basal conjugated diene concentration [a direct measurement of
      circulating oxLDL (oxidatively modified LDL)], lipoprotein particle size by NMR
      spectroscopy, PON-1 polymorphisms (coding region polymorphisms Q192R and L55M,
      and gene promoter polymorphisms -108C/T and -162G/A), PON activity (with paraoxon
      or phenyl acetate as the substrates) and dietary antioxidant intake. Plasma oxLDL
      concentrations were higher in Type II diabetic patients (males, P = 0.048;
      females, P = 0.009) and unrelated to NMR lipoprotein size, PON-1 polymorphisms or
      PON activity (with paraoxon as the substrate) in any group. In men with Type II
      diabetes, however, there was a direct relationship between oxLDL concentrations
      and PON activity (with phenyl acetate as the substrate; r = 0.611, P = 0.0001)
      and an atherogenic NMR lipid profile in those who were PON-1 55LL homozygotes.
      Circulating oxLDL concentrations in vivo were unrelated to PON-1 genotypes or
      activity, except in male Type II diabetics where there was a direct association
      between PON activity (with phenyl acetate as the substrate) and oxLDL levels.
      These in vivo data contrast with in vitro data, and may be due to confounding by
      dietary fat intake. Male Type II diabetic subjects with PON-1 55LL homozygosity
      have an atherogenic NMR lipid profile independent of LDL oxidation. These data do
      not support an in vivo action of PON on LDL oxidation.

PMID- 15853771
TI  - Miniature bioreactors for automated high-throughput bioprocess design (HTBD):
      reproducibility of parallel fed-batch cultivations with Escherichia coli.
AB  - To verify the reproducibility of cultivations of Escherichia coli in novel
      millilitre-scale bioreactors, fully automated fed-batch cultivation was performed
      in seven parallel-operated ml-scale bioreactors with an initial volume of 10
      ml/reactor. The process was automatically controlled by a liquid-handling system
      responsible for glucose feeding, titration and sampling. Atline analysis (carried
      out externally of the reaction vessel with a short time delay) comprised
      automated pH and attenuance measurements. The partial pressure of oxygen (pO2)
      was measured online by a novel fluorimetric sensor block measuring the
      fluorescence lifetime of fluorophors immobilized inside the millilitre-scale
      bioreactors. Within a process time of 14.6 h, the parallel cultivation yielded a
      dry cell weight of 36.9+/-0.9 g.l(-1). Atline pH measurements were characterized
      by an S.D. of <1.1% throughout the process. Computational-fluid-dynamics
      simulation of single-phase flow yields a mean power input of 21.9 W.l(-1) at an
      impeller speed of 2800 rev./min corresponding to a power number (NP) of 3.7.

PMID- 15853772
TI  - Triptan-induced contractile (5-HT1B receptor) responses in human cerebral and
      coronary arteries: relationship to clinical effect.
AB  - Triptans are agonists at 5-HT1B and 5-HT1D (where 5-HT is 5-hydroxytryptamine;
      serotonin) receptors and cause vasoconstriction of isolated blood vessels. The
      aim of the present study was to determine vasoconstrictor potency (EC50) of
      triptans in human coronary and cerebral arteries and to examine whether there was
      any relationship with the maximal plasma concentrations (Cmax; nM) of the drugs
      achieved following oral administration of clinically relevant doses to man using
      values reported in the literature. We also examined the expression of 5-HT1B
      receptors in atherosclerotic and normal coronary arteries. The vasocontractile
      responses to sumatriptan, rizatriptan or eletriptan were characterized by in
      vitro pharmacology. The ratio of Cmax/EC50 was calculated. 5-HT1B and 5-HT1D
      receptors were visualized by immunohistochemical techniques in coronary arteries.
      Sumatriptan, rizatriptan and eletriptan were powerful vasoconstrictors in
      cerebral artery. The rank order of agonist potency was
      eletriptan=rizatriptan=sumatriptan. In the coronary artery, the triptans were
      weaker vasoconstrictors. The rank order of potency was similar. In cerebral
      artery the ratio of Cmax/EC50 was not significantly different from unity,
      indicating a relationship between these two parameters. In general for the
      coronary artery, the ratios were significantly less than unity, indicating no
      direct relationship. Immunohistochemistry showed expression of 5-HT1B receptors
      in the medial layer, but did not reveal any obvious difference in 5-HT1B receptor
      expression between normal and atherosclerotic coronary arteries. The results
      support the notion that triptans are selective vasoconstrictors of cerebral
      arteries over coronary arteries and that there is a relationship between
      vasoconstrictor potency in cerebral arteries and clinically relevant plasma
      levels.

PMID- 15853773
TI  - The human D-glucuronyl C5-epimerase gene is transcriptionally activated through
      the beta-catenin-TCF4 pathway.
AB  - Heparan sulphate (HS) is a ubiquitous constituent of the extracellular matrix
      that is required for the biological activity of circulating soluble and insoluble
      extracellular ligands. GLCE (D-glucuronyl C5-epimerase), an enzyme responsible
      for the epimerization of D-glucuronic acid into L-iduronic acid of HS, endows the
      nascent polysaccharide chain with the ability to bind to growth factors and
      cytokines. In order to examine the mechanism of regulation of GLCE expression,
      the functional organization of the human GLCE gene promoter has been
      investigated. Studies utilizing stepwise deleted and site-directed mutagenized
      promoter constructs have shed light on the functional relevance of two cis-acting
      binding elements for the beta-catenin-TCF4 complex (where TCF4 stands for T-cell
      factor 4) that are located in the enhancer region of the promoter. The ability of
      the putative binding sequences to bind the beta-catenin-TCF4 complex has been
      confirmed through electrophoretic mobility-shift and supershift analyses. We have
      found that, in a set of human colon carcinoma cell lines, the expression of GLCE
      correlates with the degree of activation of the beta-catenin-TCF4 transactivation
      complex. Furthermore, the ectopic expression of beta-catenin-TCF4 in cells that
      constitutively express low levels of the transactivation complex produces a
      significant increase of GLCE transcript level and, at the same time, enhances the
      rate of D-glucuronic acid epimerization in HS. The data obtained are consistent
      with the idea that the beta-catenin-TCF4 transactivation pathway plays a major
      role in modulating GLCE expression, thus contributing to the regulation of HS
      biosynthesis and its structural organization.

PMID- 15853775
TI  - Shiga toxin B-subunit binds to the chaperone BiP and the nucleolar protein B23.
AB  - BACKGROUND INFORMATION: In many cell lines, such as HeLa cells, STxB (Shiga toxin
      B-subunit) is transported from the plasma membrane to the ER (endoplasmic
      reticulum), via early/recycling endosomes and the Golgi apparatus, bypassing the
      late endocytic pathway. In human monocyte-derived macrophages and dendritic cells
      that are not sensitive to Shiga toxin-induced protein biosynthesis inhibition,
      STxB is not detectably targeted to the retrograde route and is degraded in late
      endosomes/lysosomes. RESULTS: We have identified B-subunit interacting proteins
      in HeLa cells and macrophages. In HeLa cells, the ER-localized chaperone BiP
      (binding protein) was co-immunoprecipitated with the B-subunit. This interaction
      was not observed in macrophages, consistent with our previous trafficking
      results. In both cell types, the B-subunit also interacted with the nucleolar
      protein B23. Consistently, the B-subunit could be detected on nucleoli,
      suggesting that it could serve to bring the holotoxin to the site of synthesis of
      its molecular target, rRNA. The nucleolar localization data are critically
      discussed. CONCLUSION: The interaction of STxB with BiP, involved in the
      retrotranslocation process to the cytosol and nucleolar B23, as described in this
      study, might be of relevance for explaining the efficiency of even low doses of
      Shiga toxin to inactivate cellular ribosomes, and for the use of STxB as a vector
      for targeting antigens to cytosolic proteasomes of the MHC I-restricted antigen
      presentation pathway.

PMID- 15853774
TI  - Matriptase-3 is a novel phylogenetically preserved membrane-anchored serine
      protease with broad serpin reactivity.
AB  - We report in the present study the bioinformatic identification, molecular
      cloning and biological characterization of matriptase-3, a novel membrane
      anchored serine protease that is phylogenetically preserved in fish, birds,
      rodents, canines and primates. The gene encoding matriptase-3 is located on
      syntenic regions of human chromosome 3q13.2, mouse chromosome 16B5, rat
      chromosome 11q21 and chicken chromosome 1. Bioinformatic analysis combined with
      cDNA cloning predicts a functional TTSP (type II transmembrane serine protease)
      with 31% amino acid identity with both matriptase/MT-SP1 and matriptase-2. This
      novel protease is composed of a short N-terminal cytoplasmic region followed by a
      transmembrane domain, a stem region with one SEA, two CUB and three LDLRa (low
      density lipoprotein receptor domain class A) domains and a C-terminal catalytic
      serine protease domain. Transcript analysis revealed restricted, species
      conserved expression of matriptase-3, with the highest mRNA levels in brain,
      skin, reproductive and oropharyngeal tissues. The full-length matriptase-3 cDNA
      directed the expression of a 90 kDa N-glycosylated protein that localized to the
      cell surface, as assessed by cell-surface biotin labelling. The purified
      activated matriptase-3 serine protease domain expressed in insect cells
      hydrolysed synthetic peptide substrates, with a strong preference for Arg at
      position P(1), and showed proteolytic activity towards several macromolecular
      substrates, including gelatin, casein and albumin. Interestingly, activated
      matriptase-3 formed stable inhibitor complexes with an array of serpins,
      including plasminogen activator inhibitor-1, protein C inhibitor, alpha1
      proteinase inhibitor, alpha2-antiplasmin and antithrombin III. Our study
      identifies matriptase-3 as a novel biologically active TTSP of the matriptase
      subfamily having a unique expression pattern and post-translational regulation.

PMID- 15853776
TI  - Exploring Web-based resources to support the family history public health
      initiative.

PMID- 15853777
TI  - Caring for ourselves.

PMID- 15853778
TI  - Dimensions of the transition service coordinator role.
AB  - ISSUES AND PURPOSE: This article describes the development and implementation of
      an innovative advanced practice role, as a transition service coordinator for
      nurses who work with adolescents with special healthcare needs. Transition
      services for adolescents with special healthcare needs is an area of growing
      clinical need requiring that all healthcare professionals, including advanced
      practice nurses develop new clinical knowledge and skills to practice
      effectively. CONCLUSION: This emerging specialty area will require advanced
      practice nurses to provide direct services blending both pediatric and adult
      healthcare needs and to function in advanced practice roles such as case managers
      who can ensure the coordination of services between these two very different
      systems of care while promoting the youth's acquisition of goals for adulthood.
      This nursing role was first created to provide and coordinate transition services
      to youth seen in a piloted clinic titled Creating Healthy Futures. PRACTICE
      IMPLICATIONS: This article describes the various components of this nursing role
      that incorporated the advanced practice dimensions of clinical expert,
      consultant, change agent, leader, researcher, and educator that can be replicated
      in other clinical settings.

PMID- 15853779
TI  - Are all children equal? An analysis of the predictive value of selected pediatric
      characteristics of the referral of children to pediatric home health services.
AB  - ISSUES AND PURPOSE: To examine the predictive value of selected pediatric
      characteristics of the referral of children to pediatric home health services
      (PHHS). No empirical studies to date have evaluated the criteria used to
      determine the need for PHHS or if disparities in the referral of children to PHHS
      occur. DESIGN AND METHODS: Randomly selected hospital records of 557 children
      discharged from one pediatric hospital between October 1999 and September 2000
      were examined. Sequential logistic regression was used to calculate the odds of
      being referred to PHHS based on age, race or ethnicity, number of legal guardians
      in the household, and the number of technological devices at discharge. Insurance
      was excluded as a predictor because 97% of the study sample was insured. RESULTS:
      Only the number of technological devices at discharge added predictive value
      (chi(2)[DF = 3, N= 557]= 42.023, P<0.001) to the SLR model. There was no evidence
      of disparities in referral. IMPLICATIONS FOR PRACTICE: To ensure availability and
      equitable access to PHHS, nurses must actively participate in the discharge
      planning process for all children.

PMID- 15853780
TI  - Conflicts between young adolescents with type I diabetes and their parents.
AB  - ISSUES AND PURPOSE: The purposes were to describe sources of parent-adolescent
      conflict in families of young adolescents with type I diabetes and to determine
      if the sources of conflict were similar to those in a comparable nondistressed
      group from an earlier study. DESIGN AND METHODS: A descriptive study of 161
      adolescents with type I diabetes and their parents examined conflict using the
      Issues Checklist. RESULTS: Adolescents with type I diabetes and their families
      were similar to a non-distressed population in their ranking of quantity,
      intensity, and frequency by intensity scores. Issues generating the highest
      frequency of discussion were comparable to those reported in the nondistressed
      group, with the exception of topics regarding what time to have meals and to
      watch television. Intensity of discussion was also comparable, with the exception
      of topics regarding getting up in the morning and bothering the parents.
      Adolescent report of conflict with the mother was significantly lower overall for
      the adolescents with type I diabetes. PRACTICE IMPLICATIONS: Conflict is expected
      between young adolescents and parents, and having type I diabetes does not
      heighten conflict with parents with respect to general adolescent issues.
      Understanding this principle should help healthcare workers recognize usual
      adolescent-parent conflict and use similar approaches to address these conflicts
      as are used with nondistressed families.

PMID- 15853782
TI  - Nontraditional therapies for the PICU--part 2.

PMID- 15853783
TI  - Spinal cord injury interdisciplinary education.

PMID- 15853784
TI  - From research idea to research question: the who, what, where, when, and why.

PMID- 15853785
TI  - Family-centered care: a case study.

PMID- 15853786
TI  - A broader view of evidence.

PMID- 15853787
TI  - Physical and chemical restraints in acute care: their potential impact on the
      rehabilitation of older people.
AB  - Agitation is a major problem for older people and is present in over half of the
      hospitalizations for people > 65 years of age. In a previous study by the
      authors, results indicated that nursing actions often did not meet best-practice
      standards in the care of older, agitated patients. This paper builds on these
      results by reviewing the literature pertaining to the use of restraints and
      contributes to the body of knowledge surrounding the impact of the acute-care
      experience on rehabilitation outcomes. Successful rehabilitation relies on the
      improvement of functional health outcomes and, for this to happen, physical and
      emotional well-being are important. The sequelae of restraint use in acute care
      have the potential to alter peoples' ability to participate fully in a
      rehabilitation programme, thereby placing their future placement at risk. This
      paper explores the outcomes of restraint use in the acute-care setting and
      presents the argument that their effects are likely to be detrimental to
      rehabilitation outcomes.

PMID- 15853788
TI  - Relationships in nurse prescribing in district nursing practice in England: a
      preliminary investigation.
AB  - Nurse prescribing is a significant change in the working lives of district nurses
      in the United Kingdom. It has been achieved as the result of a 13-year
      sociopolitical struggle, eventually culminating in an Act of Parliament, which
      enabled selected nurses to prescribe from a limited formulary. This research
      attempts to discover the nature of its impact on the relationships between
      prescribers, nurses, doctors, pharmacists, patients and carers. Using a
      qualitative approach, guided interviews were carried out with nurses, doctors,
      pharmacists, patients and carers. Initial findings indicate that far from
      producing an independent prescribing workforce, some prescribers are reverting to
      their preprescribing behaviour. For these prescribers, there is a suggestion that
      old hierarchies are being reinforced, which might be detrimental to nurse
      prescribing.

PMID- 15853789
TI  - The role of the neonatal intensive care nurse in decision-making: advocacy,
      involvement in ethical decisions and communication.
AB  - Neonatal intensive care unit (NICU) nurses are often faced with complex clinical
      and ethical problems. Little is known about the role of the NICU nurse in ethical
      decision-making, or processes that inform decision-making in this setting. The
      purpose of this study was to explore and describe nurses' perceptions of their
      role as patient advocate, clinical situations that cause them concern and the
      extent of their involvement in ethical decision-making. A combined quantitative
      and qualitative research design was used. A questionnaire was administered to
      nurses working in the NICU of the sole perinatal tertiary referral centre of
      Western Australia, Australia. Findings showed that NICU nurses saw their role in
      ethical decision-making primarily as advocating for the best interests of the
      infant and family, that they used clinical knowledge and experience to guide
      ethical decision-making, they were able to clearly articulate ethical problems
      and respond to them according to the clinical scenario and, while being primarily
      assertive in presenting their views, some nurses took a more passive approach.
      These findings support the need for development of a multidisciplinary model for
      ethical decision-making, where the view of all team members are considered.

PMID- 15853790
TI  - Finding the balance: living with memory loss.
AB  - Since the late 1980s, it has been increasingly recognized that the experiences of
      people with dementia have been omitted from research in the area of dementia and
      memory loss. More recently, it has been accepted that people with dementia have
      insight into their condition and, therefore, the ability to contribute to
      research. A qualitative research project was undertaken with nine participants to
      explore the experiences and coping strategies of people with dementia. Interviews
      were undertaken and the data analysed using thematic analysis. Three major themes
      emerged: coming to terms with memory loss, maintaining control and independence,
      and the impact of illness on relationships. Understanding the reality for people
      is essential given that representations of the catastrophic impact of dementia
      generate high levels of anxiety and depression. Implications for nurses' practice
      include the need for skilled, well-paced, sensitive and ongoing information about
      the condition, along with the need to recognize and support the active coping
      strategies of people with memory loss.

PMID- 15853791
TI  - Familial contribution to adolescent subjective well-being.
AB  - The purpose of this study was to obtain a more complete understanding of which
      familial factors contribute to adolescent satisfaction and ill-being, the latter
      term originally developed by Alexander Grob. Semistructured interviews were
      conducted with 19 non-clinical adolescents from the 7th and 9th grades. The data
      were analysed using qualitative content analysis. Six themes concerning
      satisfaction arose from the analysis. Teenagers described familial contribution
      to their satisfaction in terms of experiences of a comfortable home, emotionally
      warm atmosphere, open communication, familial involvement, possibilities for
      external relations and a sense of personal significance in the family. Three
      themes related to ill-being emerged: familial hostility, ill-being or death of a
      family member, as well as excessive dependency. The findings expand our
      understanding of the diversity of familial contribution to adolescent life and
      subjective well-being. They challenge nurses to focus on the adolescent's self
      perception of familial effects on well-being and on promotion of familial factors
      in adolescent health issues.

PMID- 15853792
TI  - A clinical development unit in cardiology: the way forward.
AB  - The clinical development unit (CDU) has been recognized as an effective strategy
      to progress creativity and resourcefulness in nursing practice to improve patient
      outcomes. Clinical development units, through transformational leadership,
      promote staff development, the use of research evidence and dissemination of
      research findings through publication and presentations. The aim of this paper is
      to clearly articulate the processes (in particular, research and education
      initiatives) related to the development of staff that address issues in the
      everyday workplace and, accordingly, have been instrumental in the success of the
      creation of a CDU in cardiology. These units aim to achieve and promote
      excellence in an identifiable area of nursing using a systematic, transparent and
      defensible approach. A review of acute coronary syndrome informed the needs and
      direction of staff activities in the cardiology unit of a tertiary referral
      hospital. Through a collaborative staff approach, evidence was carefully examined
      to plan its appropriate adoption into the clinical area. Nursing practice and
      education resulting from this review was scheduled into staff career progression.
      These initiatives have been incorporated into staff development learning,
      enabling the integration of research into practice, which ultimately has a
      positive impact on patient outcomes.

PMID- 15853794
TI  - Protein families and RNA recognition.
AB  - This minireview series examines the structural principles underlying the
      biological function of RNA-binding proteins. The structural work of the last
      decade has elucidated the structures of essentially all the major RNA-binding
      protein families; it has also demonstrated how RNA recognition takes place. The
      ribosome structures have further integrated this knowledge into principles for
      the assembly of complex ribonucleoproteins. Structural and biochemical work has
      revealed unexpectedly that several RNA-binding proteins bind to other proteins in
      addition to RNA or instead of RNA. This tremendous increase in the structural
      knowledge has expanded not only our understanding of the RNA recognition
      principle, but has also provided new insight into the biological function of
      these proteins and has helped to design better experiments to understand their
      biological roles.

PMID- 15853795
TI  - The social life of ribosomal proteins.
AB  - Ribosomal proteins hold a unique position in biology because their function is so
      closely tied to the large rRNAs of the ribosomes in all kingdoms of life.
      Following the determination of the complete crystal structures of both the large
      and small ribosomal subunits from bacteria, the functional role of the proteins
      has often been overlooked when focusing on rRNAs as the catalysts of translation.
      In this review we highlight some of the many known and important functions of
      ribosomal proteins, both during translation on the ribosome and in a wider
      context.

PMID- 15853796
TI  - The double-stranded RNA-binding motif, a versatile macromolecular docking
      platform.
AB  - The double-stranded RNA-binding motif (dsRBM) is an alphabetabetabetaalpha fold
      with a well-characterized function to bind structured RNA molecules. This motif
      is widely distributed in eukaryotic proteins, as well as in proteins from
      bacteria and viruses. dsRBM-containing proteins are involved in processes ranging
      from RNA editing to protein phosphorylation in translational control and contain
      a variable number of dsRBM domains. The structural work of the past five years
      has identified a common mode of RNA target recognition by dsRBMs and dissected
      this recognition into two functionally separated interaction modes. The first
      involves the recognition of specific moieties of the RNA A-form helix by two
      protein loops, while the second is based on the interaction between structural
      elements flanking the RNA duplex with the first helix of the dsRBM. The latter
      interaction can be tuned by other protein elements. Recent work has made clear
      that dsRBMs can also recognize non-RNA targets (proteins and DNA), and act in
      combination with other dsRBMs and non-dsRBM motifs to play a regulatory role in
      catalytic processes. The elucidation of functional networks coordinated by dsRBM
      folds will require information on the precise functional relationship between
      different dsRBMs and a clarification of the principles underlying dsRBM-protein
      recognition.

PMID- 15853797
TI  - The RNA recognition motif, a plastic RNA-binding platform to regulate post
      transcriptional gene expression.
AB  - The RNA recognition motif (RRM), also known as RNA-binding domain (RBD) or
      ribonucleoprotein domain (RNP) is one of the most abundant protein domains in
      eukaryotes. Based on the comparison of more than 40 structures including 15
      complexes (RRM-RNA or RRM-protein), we reviewed the structure-function
      relationships of this domain. We identified and classified the different
      structural elements of the RRM that are important for binding a multitude of RNA
      sequences and proteins. Common structural aspects were extracted that allowed us
      to define a structural leitmotif of the RRM-nucleic acid interface with its
      variations. Outside of the two conserved RNP motifs that lie in the center of the
      RRM beta-sheet, the two external beta-strands, the loops, the C- and N-termini,
      or even a second RRM domain allow high RNA-binding affinity and specific
      recognition. Protein-RRM interactions that have been found in several structures
      reinforce the notion of an extreme structural versatility of this domain
      supporting the numerous biological functions of the RRM-containing proteins.

PMID- 15853798
TI  - Mammalian mitotic centromere-associated kinesin (MCAK): a new molecular target of
      sulfoquinovosylacylglycerols novel antitumor and immunosuppressive agents.
AB  - Sulfoquinovosylacylglycerols (SQAGs), in particular compounds with C18 fatty
      acid(s) on the glycerol moiety, may be clinically promising antitumor and/or
      immunosuppressive agents. They were found originally as inhibitors of mammalian
      DNA polymerases. However, SQAGs can arrest cultured mammalian cells not only at S
      phase but also at M phase, suggesting they have several molecular targets. A
      screen for candidate target molecules using a T7 phage display method identified
      an amino acid sequence. An homology search showed this to be a mammalian mitotic
      centromere-associated kinesin (MCAK), rather than a DNA polymerase. Analyses
      showed SQAGs bound to recombinant MCAK with a K(D)=3.1x10(-4) to 6.2x10-5 M. An
      in vivo microtubule depolymerization assay, using EGFP-full length MCAK fusion
      constructs, indicated inhibition of the microtubule depolymerization activity of
      MCAK. From these results, we conclude that clinically promising SQAGs have at
      least two different molecular targets, DNA polymerases and MCAK. It should be
      stressed that inhibitors of MCAK have never been reported previously so that
      there is a major potential for clinical utility.

PMID- 15853799
TI  - Identification of small scale biochemical networks based on general type system
      perturbations.
AB  - New technologies enable acquisition of large data-sets containing genomic,
      proteomic and metabolic information that describe the state of a cell. These data
      sets call for systematic methods enabling relevant information about the inner
      workings of the cell to be extracted. One important issue at hand is the
      understanding of the functional interactions between genes, proteins and
      metabolites. We here present a method for identifying the dynamic interactions
      between biochemical components within the cell, in the vicinity of a steady
      state. Key features of the proposed method are that it can deal with data
      obtained under perturbations of any system parameter, not only concentrations of
      specific components, and that the direct effect of the perturbations does not
      need to be known. This is important as concentration perturbations are often
      difficult to perform in biochemical systems and the specific effects of general
      type perturbations are usually highly uncertain, or unknown. The basis of the
      method is a linear least-squares estimation, using time-series measurements of
      concentrations and expression profiles, in which system states and parameter
      perturbations are estimated simultaneously. An important side-effect of also
      employing estimation of the parameter perturbations is that knowledge of the
      system's steady-state concentrations, or activities, is not required and that
      deviations from steady-state prior to the perturbation can be dealt with. Time
      derivatives are computed using a zero-order hold discretization, shown to yield
      significant improvements over the widely used Euler approximation. We also show
      how network interactions with dynamics that are too fast to be captured within
      the available sampling time can be determined and excluded from the network
      identification. Known and unknown moiety conservation relationships can be
      processed in the same manner. The method requires that the number of samples
      equals at least the number of network components and, hence, is at present
      restricted to relatively small-scale networks. We demonstrate herein the
      performance of the method on two small-scale in silico genetic networks.

PMID- 15853800
TI  - Conformational heterogeneity of transmembrane residues after the Schiff base
      reprotonation of bacteriorhodopsin: 15N CPMAS NMR of D85N/T170C membranes.
AB  - bR, N-like and O-like intermediate states of [15N]methionine-labelled wild type
      and D85N/T170C bacteriorhodopsin were accumulated in native membranes by
      controlling the pH of the preparations. 15N cross polarization and magic angle
      sample spinning (CPMAS) NMR spectroscopy allowed resolution of seven out of nine
      resonances in the bR-state. It was possible to assign some of the observed
      resonances by using 13C/15N rotational echo double resonance (REDOR) NMR and Mn2+
      quenching as well as D2O exchange, which helps to identify conformational changes
      after the bacteriorhodopsin Schiff base reprotonation. The significant
      differences in chemical shifts and linewidths detected for some of the resonances
      in N- and O-like samples indicate changes in conformation, structural
      heterogeneity or altered molecular dynamics in parts of the protein.

PMID- 15853801
TI  - Functional dissection of two Arabidopsis PsbO proteins: PsbO1 and PsbO2.
AB  - PsbO protein is an extrinsic subunit of photosystem II (PSII) and has been
      proposed to play a central role in stabilization of the catalytic manganese
      cluster. Arabidopsis thaliana has two psbO genes that express two PsbO proteins;
      PsbO1 and PsbO2. We reported previously that a mutant plant that lacked PsbO1
      (psbo1) showed considerable growth retardation despite the presence of PsbO2
      [Murakami, R., Ifuku, K., Takabayashi, A., Shikanai, T., Endo, T., and Sato, F.
      (2002) FEBS Lett523, 138-142]. In the present study, we characterized the
      functional differences between PsbO1 and PsbO2. We found that PsbO1 is the major
      isoform in the wild-type, and the amount of PsbO2 in psbo1 was significantly less
      than the total amount of PsbO in the wild-type. The amount of PsbO as well as the
      efficiency of PSII in psbo1 increased as the plants grew; howeVER, it neVER
      reached the total PsbO level observed in the wild-type, suggesting that the poor
      activity of PSII in psbo1 was caused by a shortage of PsbO. In addition, an in
      vitro reconstitution experiment using recombinant PsbOs and urea-washed PSII
      particles showed that oxygen evolution was better recoVERed by PsbO1 than by
      PsbO2. Further analysis using chimeric and mutated PsbOs suggested that the amino
      acid changes Val186-->Ser, Leu246-->Ile, and Val204-->Ile could explain the
      functional difference between the two PsbOs. Therefore we concluded that both the
      lower expression level and the inferior functionality of PsbO2 are responsible
      for the phenotype observed in psbo1.

PMID- 15853802
TI  - Protein dissection enhances the amyloidogenic properties of alpha-lactalbumin.
AB  - Alpha-lactalbumin (LA) in its molten globule (MG) state at low pH forms amyloid
      fibrils. Here, we have studied the aggregation propensities of LA derivatives
      characterized by a single peptide bond fission (1-40/41-123, named Th1-LA) or a
      deletion of a chain segment of 12 amino acid residues located at the level of the
      beta-subdomain of the native protein (1-40/53-123, named desbeta-LA). We have
      also compared the early stages of the aggregation process of these LA derivatives
      with those of intact LA. Th1-LA and desbeta-LA aggregate at pH 2.0 much faster
      than the intact protein and form long and well-ordered fibrils. Furthermore, in
      contrast to intact LA, the LA derivatives form regular fibrils also at neutral
      pH, even if at much reduced rate. In acidic solution, Th1-LA and desbeta-LA adopt
      a MG state which appears to be similar to that of intact LA, as given by
      spectroscopic criteria. At neutral pH, both Th1-LA and desbeta-LA are able to
      bind the hydrophobic dye 1-anilinonaphtalene-8-sulfonate, thus indicating the
      presence of exposed hydrophobic patches. It is concluded that nicked Th1-LA and
      gapped desbeta-LA are more relaxed and expanded than intact LA and, consequently,
      that they are more suitable protein species to allow the large conformational
      transitions required for the polypeptide chain to form the amyloid cross-beta
      structure. As a matter of fact, the MG of LA attains an even more flexible
      conformational state during the early phases of the aggregation process at acidic
      pH, as deduced from the enhancement of its susceptibility to proteolysis by
      pepsin. Our data indicate that deletion of the beta-subdomain in LA does not
      alter the ability of the protein to assemble into well-ordered fibrils, implying
      that this chain region is not essential for the amyloid formation. It is proposed
      that a proteolytic hydrolysis of a protein molecule at the cellular level can
      trigger an easier formation of amyloid precipitates and therefore that limited
      proteolysis of proteins can be a causative mechanism of protein aggregation and
      fibrillogenesis. Indeed, a vast majority of protein deposits in amyloid diseases
      are given by protein fragments derived from larger protein precursors.

PMID- 15853803
TI  - The two IQ-motifs and Ca2+/calmodulin regulate the rat myosin 1d ATPase activity.
AB  - The light chain binding domain of rat myosin 1d consists of two IQ-motifs, both
      of which bind the light chain calmodulin (CaM). To analyze the Myo1d ATPase
      activity as a function of the IQ-motifs and Ca2+/CaM binding, we expressed and
      affinity purified the Myo1d constructs Myo1d-head, Myo1d-IQ1, Myo1d-IQ1.2, Myo1d
      IQ2 and Myo1dDeltaLV-IQ2. IQ1 exhibited a high affinity for CaM both in the
      absence and presence of free Ca2+. IQ2 had a lower affinity for CaM in the
      absence of Ca2+ than in the presence of Ca2+. The actin-activated ATPase activity
      of Myo1d was approximately 75% inhibited by Ca2+-binding to CaM. This inhibition
      was observed irrespective of whether IQ1, IQ2 or both IQ1 and IQ2 were fused to
      the head. Based on the measured Ca2+-dependence, we propose that Ca2+-binding to
      the C-terminal pair of high affinity sites in CaM inhibits the Myo1d actin
      activated ATPase activity. This inhibition was due to a conformational change of
      the C-terminal lobe of CaM remaining bound to the IQ-motif(s). Interestingly, a
      similar but Ca2+-independent inhibition of Myo1d actin-activated ATPase activity
      was observed when IQ2, fused directly to the Myo1d-head, was rotated through 200
      degrees by the deletion of two amino acids in the lever arm alpha-helix N
      terminal to the IQ-motif.

PMID- 15853804
TI  - Crystal structures of Aedes aegypti kynurenine aminotransferase.
AB  - Aedes aegypti kynurenine aminotransferase (AeKAT) catalyzes the irreversible
      transamination of kynurenine to kynurenic acid, the natural antagonist of NMDA
      and 7-nicotinic acetycholine receptors. Here, we report the crystal structure of
      AeKAT in its PMP and PLP forms at 1.90 and 1.55 A, respectively. The structure
      was solved by a combination of single-wavelength anomalous dispersion and
      molecular replacement approaches. The initial search model in the molecular
      replacement method was built with the result of single-wavelength anomalous
      dispersion data from the Br-AeKAT crystal in combination with homology modeling.
      The solved structure shows that the enzyme is a homodimer, and that the two
      subunits are stabilized by a number of hydrogen bonds, salts bridges, and
      hydrophobic interactions. Each subunit is divided into an N-terminal arm and
      small and large domains. Based on its folding, the enzyme belongs to the
      prototypical fold type, aminotransferase subgroup I. The three-dimensional
      structure shows a strictly conserved 'PLP-phosphate binding cup' featuring PLP
      dependent enzymes. The interaction between Cys284 (A) and Cys284 (B) is unique in
      AeKAT, which might explain the cysteine effect of AeKAT activity. Further
      mutation experiments of this residue are needed to eventually understand the
      mechanism of the enzyme modulation by cysteine.

PMID- 15853805
TI  - Development of an HSV-tk transgenic mouse model for study of liver damage.
AB  - The herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system that
      selectively depletes cells expressing HSV-tk upon treatment with GCV has provided
      a valuable tool for developing a new animal model expressing the desired tissue
      damage. In this paper, an HSV-tk vector with an albumin promoter/enhancer was
      constructed. Based on the favourable killing effect on Hep-G2 cells by the
      recombinant construct, the HSV-tk transgenic mouse strains were developed. One
      strain of the TK transgenic mouse (TK5) was studied intensively. Integration of
      the target gene was confirmed primarily by PCR. Fluorescence in situ
      hybridization following G-banding analysis demonstrated that the insertion site
      was located at 2F1-G3. The hepatocyte-specific transcription and expression of
      HSV-tkwas verified by reverse transcription (RT)-PCR as well as by
      immunohistochemical staining. When two second-generation mice (TK5-F1 and TK5-F2)
      were injected with GCV, the pathogenic alterations in the liver were readily
      identified, including the appearance of vaculation in the hepatocytes with
      inflammatory infiltration in the liver, and diffuse proliferation of hepatocytes.
      In addition, the blood test demonstrates a significant increase of serum alanine
      aminotransferase, aspartate aminotransferase and total bilirubin. In conclusion,
      the transgenic mouse model with hepatocyte-specific expressed HSV-tk developed
      hepatitis with administration of GCV, had morphological and clinical chemical
      characteristics indicative of hepatocellular disease and should be useful for the
      the study of inducible liver-specific diseases.

PMID- 15853806
TI  - Guanidinium chloride- and urea-induced unfolding of FprA, a mycobacterium NADPH
      ferredoxin reductase: stabilization of an apo-protein by GdmCl.
AB  - The guanidinium chloride- and urea-induced unfolding of FprA, a mycobacterium
      NADPH-ferredoxin reductase, was examined in detail using multiple spectroscopic
      techniques, enzyme activity measurements and size exclusion chromatography. The
      equilibrium unfolding of FprA by urea is a cooperative process where no
      stabilization of any partially folded intermediate of protein is observed. In
      comparison, the unfolding of FprA by guanidinium chloride proceeds through
      intermediates that are stabilized by interaction of protein with guanidinium
      chloride. In the presence of low concentrations of guanidinium chloride the
      protein undergoes compaction of the native conformation; this is due to
      optimization of charge in the native protein caused by electrostatic shielding by
      the guanidinium cation of charges on the polar groups located on the protein side
      chains. At a guanidinium chloride concentration of about 0.8 m, stabilization of
      apo-protein was observed. The stabilization of apo-FprA by guanidinium chloride
      is probably the result of direct binding of the Gdm+ cation to protein. The
      results presented here suggest that the difference between the urea- and
      guanidinium chloride-induced unfolding of FprA could be due to electrostatic
      interactions stabilizating the native conformation of this protein.

PMID- 15853807
TI  - Analysis of active-site amino-acid residues of human serum paraoxonase using
      competitive substrates.
AB  - Serum paraoxonase (PON1) is a calcium-dependent six-fold beta-propeller protein
      structurally similar to the di-isopropylfluorophosphatase (DFPase) found in the
      squid Loligo vulgaris. Human serum paraoxonase (HuPON1) has been shown to
      hydrolyze an array of substrates even though relatively little is known about its
      physiological role(s) or its catalytic mechanism. Through site-directed
      mutagenesis studies, designed from a DFPase-like homology model, and from a
      crystal structure of a hybrid PON1 molecule, amino-acid residues essential for
      enzyme function, including H115 and F222, have been identified. It was shown
      previously that, when H115 is replaced with tryptophan, the resulting enzyme
      hydrolyzes paraoxon but not phenyl acetate. This study shows that, when present
      simultaneously, phenyl acetate competitively inhibits paraoxon hydrolysis by
      H115W. Conversely, when F222 is replaced with tyrosine, mutant F222Y can
      hydrolyze phenyl acetate but not paraoxon. The presence of DFP, an inhibitor of
      both arylesterase and paraoxonase activities of wild-type HuPON1 (mean Ki=0.48+/
      0.15 mM), has no effect on the ability of F222Y to catalyze the hydrolysis of
      phenyl acetate, suggesting that the F222Y mutant is unable to bind DFP. Together,
      the results suggest that, in wild-type HuPON1, H115 and F222 are important in
      determining substrate binding and specificity, but are not likely to be directly
      involved in substrate hydrolysis.

PMID- 15853808
TI  - Collagenous Alzheimer amyloid plaque component assembles amyloid fibrils into
      protease resistant aggregates.
AB  - Recently, a novel plaque-associated protein, collagenous Alzheimer amyloid plaque
      component (CLAC), was identified in brains from patients with Alzheimer's
      disease. CLAC is derived from a type II transmembrane collagen precursor protein,
      termed CLAC-P (collagen XXV). The biological function and the contribution of
      CLAC to the pathogenesis of Alzheimer's disease and plaque formation are unknown.
      In vitro studies indicate that CLAC binds to fibrillar, but not to monomeric,
      amyloid beta-peptide (Abeta). Here, we examined the effects of CLAC on Abeta
      fibrils using assays based on turbidity, thioflavin T binding, sedimentation
      analysis, and electron microscopy. The incubation of CLAC with preformed Abeta
      fibrils led to increased turbidity, indicating that larger aggregates were
      formed. In support of this contention, more Abeta was sedimented in the presence
      of CLAC, as determined by gel electrophoresis. Moreover, electron microscopy
      revealed an increased amount of Abeta fibril bundles in samples incubated with
      CLAC. Importantly, the frequently used thioflavin T-binding assay failed to
      reveal these effects of CLAC. Digestion with proteinase K or trypsin showed that
      Abeta fibrils, incubated together with CLAC, were more resistant to proteolytic
      degradation. Therefore, CLAC assembles Abeta fibrils into fibril bundles that
      have an increased resistance to proteases. We suggest that CLAC may act in a
      similar way in vivo.

PMID- 15853810
TI  - Binding of ligands originates small perturbations on the microscopic
      thermodynamic properties of a multicentre redox protein.
AB  - NMR and visible spectroscopy coupled to redox measurements were used to determine
      the equilibrium thermodynamic properties of the four haems in cytochrome c3 under
      conditions in which the protein was bound to ligands, the small anion phosphate
      and the protein rubredoxin with the iron in the active site replaced by zinc.
      Comparison of these results with data for the isolated cytochrome shows that
      binding of ligands causes only small changes in the reduction potentials of the
      haems and their pairwise interactions, and also that the redox-sensitive acid
      base centre responsible for the redox-Bohr effect is essentially unaffected.
      Although neither of the ligands tested is a physiological partner of cytochrome
      c3, the small changes observed for the thermodynamic properties of cytochrome c3
      bound to these ligands vs. the unbound state, indicate that the thermodynamic
      properties measured for the isolated protein are relevant for a physiological
      interpretation of the role of this cytochrome in the bioenergetic metabolism of
      Desulfovibrio.

PMID- 15853809
TI  - Apoptosis-inhibiting activities of BIR family proteins in Xenopus egg extracts.
AB  - In many animal species including Xenopus, ovulated eggs possess an intrinsic
      apoptotic execution system. This program is inhibited for a limited time by some
      maternal apoptosis inhibitors, although their molecular properties remain
      uncharacterized. Baculovirus IAP repeat (BIR) family proteins contain
      evolutionarily conserved BIR domains and play important roles in apoptosis
      suppression, and are therefore good candidates as maternal apoptosis inhibitors.
      We identified four maternal BIR family proteins in Xenopus eggs and, using the
      biochemical advantages of egg extracts, examined their physiological functions.
      These molecules included two survivin-related proteins, xEIAP/XLX, and a possible
      ortholog of XIAP named xXIAP. The addition of recombinant xXIAP greatly delayed
      apoptotic execution, whereas the immunodepletion of endogenous xXIAP
      significantly accelerated the onset of apoptosis. In contrast, xEIAP/XLX was a
      poor apoptosis inhibitor, and neither of the survivin orthologs showed anti
      apoptotic activity in our assay. Both xEIAP/XLX and xXIAP were degraded by
      activated caspases, and also by a novel proteolytic system that required the
      presence of C-terminal RING finger domain but was insensitive to proteasome
      inhibition. Our data suggest that the regulation of endogenous xXIAP
      concentration is important for the survival of Xenopus eggs.

PMID- 15853811
TI  - Evidence for interactions between domains of TatA and TatB from mutagenesis of
      the TatABC subunits of the twin-arginine translocase.
AB  - The twin-arginine translocation (Tat) system transports folded proteins across
      the bacterial plasma membrane. Three subunits, TatA, B and C, are known to be
      involved but their modes of action are poorly understood, as are the inter
      subunit interactions occurring within Tat complexes. We have generated mutations
      in the single transmembrane (TM) spans of TatA and TatB, with the aim of
      generating structural distortions. We show that substitution in TatB of three
      residues by glycine, or a single residue by proline, has no detectable effect on
      translocation, whereas the presence of three glycines in the TatA TM span
      completely blocks Tat translocation activity. The results show that the integrity
      of the TatA TM span is vital for Tat activity, whereas that of TatB can
      accommodate large-scale distortions. Near-complete restoration of activity in
      TatA mutants is achieved by the simultaneous presence of a V12P mutation in the
      TatB TM span, strongly implying a direct functional interaction between the
      TatA/B TM spans. We also analyzed the predicted amphipathic regions in TatA and
      TatB and again find evidence of direct interaction; benign mutations in either
      subunit completely blocked translocation of two Tat substrates when present in
      combination. Finally, we have re-examined the effects of previously analyzed
      TatABC mutations under conditions of high translocation activity. Among numerous
      TatA or TatB mutations tested, TatA F39A alone blocked translocation, and only
      substitutions of P48 and F94 in TatC blocked translocation activity.

PMID- 15853812
TI  - gammaN-crystallin and the evolution of the betagamma-crystallin superfamily in
      vertebrates.
AB  - The beta and gamma crystallins are evolutionarily related families of proteins
      that make up a large part of the refractive structure of the vertebrate eye lens.
      Each family has a distinctive gene structure that reflects a history of
      successive gene duplications. A survey of gamma-crystallins expressed in mammal,
      reptile, bird and fish species (particularly in the zebrafish, Danio rerio) has
      led to the discovery of gammaN-crystallin, an evolutionary bridge between the
      beta and gamma families. In all species examined, gammaN-crystallins have a
      hybrid gene structure, half beta and half gamma, and thus appear to be the
      'missing link' between the beta and gamma crystallin lineages. Overall, there are
      four major classes of gamma-crystallin: the terrestrial group (including
      mammalian gammaA-F); the aquatic group (the fish gammaM-crystallins); the gammaS
      group; and the novel gammaN group. Like the evolutionarily ancient beta
      crystallins (but unlike the terrestrial gammaA-F and aquatic gammaM groups), both
      the gammaS and gammaN crystallins form distinct clades with members in fish,
      reptiles, birds and mammals. In rodents, gammaN is expressed in nuclear fibers of
      the lens and, perhaps hinting at an ancestral role for the gamma-crystallins,
      also in the retina. Although well conserved throughout vertebrate evolution,
      gammaN in primates has apparently undergone major changes and possible loss of
      functional expression.

PMID- 15853813
TI  - Control analysis as a tool to understand the formation of the las operon in
      Lactococcus lactis.
AB  - In Lactococcus lactis the enzymes phosphofructokinase (PFK), pyruvate kinase (PK)
      and lactate dehydrogenase (LDH) are uniquely encoded in the las operon. We used
      metabolic control analysis to study the role of this organization. Earlier
      studies have shown that, at wild-type levels, LDH has no control over glycolysis
      and growth rate, but high negative control over formate production
      (C(Jformate)LDH=-1.3). We found that PFK and PK exert no control over glycolysis
      and growth rate at wild-type enzyme levels but both enzymes exert strong positive
      control on the glycolytic flux at reduced activities. PK exerts high positive
      control over formate (C(Jformate)PK=0.9-1.1) and acetate production
      (C(Jacetate)PK=0.8-1.0), whereas PFK exerts no control over these fluxes at
      increased expression. Decreased expression of the entire las operon resulted in a
      strong decrease in the growth rate and glycolytic flux; at 53% expression of the
      las operon glycolytic flux was reduced to 44% and the flux control coefficient
      increased towards 3. Increased las expression resulted in a slight decrease in
      the glycolytic flux. At wild-type levels, control was close to zero on both
      glycolysis and the pyruvate branches. The sum of control coefficients for the
      three enzymes individually was comparable with the control coefficient found for
      the entire operon; the strong positive control exerted by PK almost cancels out
      the negative control exerted by LDH on formate production. Our analysis suggests
      that coregulation of PFK and PK provides a very efficient way to regulate
      glycolysis, and coregulating PK and LDH allows cells to maintain homolactic
      fermentation during glycolysis regulation.

PMID- 15853814
TI  - Endogenous expression and protein kinase A-dependent phosphorylation of the
      guanine nucleotide exchange factor Ras-GRF1 in human embryonic kidney 293 cells.
AB  - We have previously reported the Ras-dependent activation of the mitogen-activated
      protein kinases p44 and p42, also termed extracellular signal-regulated kinases
      (ERK)1 and 2 (ERK1/2), mediated through Gs-coupled serotonin receptors
      transiently expressed in human embryonic kidney (HEK) 293 cells. Whereas Gi- and
      Gq-coupled receptors have been shown to activate Ras through the guanine
      nucleotide exchange factor (GEF) called Ras-GRF1 (CDC25Mm) by binding of
      Ca2+/calmodulin to its N-terminal IQ domain, the mechanism of Ras activation
      through Gs-coupled receptors is not fully understood. We report the endogenous
      expression of Ras-GRF1 in HEK293 cells. Serotonin stimulation of HEK293 cells
      transiently expressing Gs-coupled 5-HT7 receptors induced protein kinase A
      dependent phosphorylation of the endogenous human Ras-GRF1 on Ser927 and of
      transfected mouse Ras-GRF1 on Ser916. Ras-GRF1 overexpression increased basal and
      serotonin-stimulated ERK1/2 phosphorylation. Mutations of Ser916 inhibiting
      (Ser916Ala) or mimicking (Ser916Asp/Glu) phosphorylation did not alter these
      effects. However, the deletion of amino acids 1-225, including the
      Ca2+/calmodulin-binding IQ domain, from Ras-GRF1 reduced both basal and serotonin
      stimulated ERK1/2 phosphorylation. Furthermore, serotonin treatment of HEK293
      cells stably expressing 5-HT7 receptors increased [Ca2+]i, and the serotonin
      induced ERK1/2 phosphorylation was Ca2+-dependent. Therefore, both cAMP and Ca2+
      may contribute to the Ras-dependent ERK1/2 activation after 5-HT7 receptor
      stimulation, through activation of a guanine nucleotide exchange factor with
      activity towards Ras.

PMID- 15853815
TI  - Determination of thioxylo-oligosaccharide binding to family 11 xylanases using
      electrospray ionization Fourier transform ion cyclotron resonance mass
      spectrometry and X-ray crystallography.
AB  - Noncovalent binding of thioxylo-oligosaccharide inhibitors, methyl 4-thio-alpha
      xylobioside (S-Xyl2-Me), methyl 4,4II-dithio-alpha-xylotrioside (S-Xyl3-Me),
      methyl 4,4II,4III-trithio-alpha-xylotetroside (S-Xyl4-Me), and methyl
      4,4II,4III,4IV-tetrathio-alpha-xylopentoside (S-Xyl5-Me), to three family 11 endo
      1,4-beta-xylanases from Trichoderma reesei (TRX I and TRX II) and Chaetomium
      thermophilum (CTX) was characterized using electrospray ionization Fourier
      transform ion cyclotron resonance (FT-ICR) MS and X-ray crystallography. Ultra
      high mass-resolving power and mass accuracy inherent to FT-ICR allowed mass
      measurements for noncovalent complexes to within |DeltaM|average of 2 p.p.m. The
      binding constants determined by MS titration experiments were in the range 10(4)
      10(3) M-1, decreasing in the series of S-Xyl5-Me>or=S-Xyl4-Me>S-Xyl3-Me. In
      contrast, S-Xyl2-Me did not bind to any xylanase at the initial concentration of
      5-200 microM, indicating increasing affinity with increasing number of
      xylopyranosyl units, with a minimum requirement of three. The crystal structures
      of CTX-inhibitor complexes gave interesting insights into the binding.
      Surprisingly, none of the inhibitors occupied any of the aglycone subsites of the
      active site. The binding to only the glycone subsites is nonproductive for
      catalysis, and yet this has also been observed for other family 11 xylanases in
      complex with beta-d-xylotetraose [Wakarchuk WW, Campbell RL, Sung WL, Davoodi J &
      Makoto Y (1994) Protein Sci3, 465-475, and Sabini E, Wilson KS, Danielsen S,
      Schulein M & Davies GJ (2001) Acta CrystallogrD57, 1344-1347]. Therefore, the
      role of the aglycone subsites remains controversial despite their obvious
      contribution to catalysis.

PMID- 15853816
TI  - Secondary transporters of the 2HCT family contain two homologous domains with
      inverted membrane topology and trans re-entrant loops.
AB  - The 2-hydroxycarboxylate transporter (2HCT) family of secondary transporters
      belongs to a much larger structural class of secondary transporters termed ST3
      which contains about 2000 transporters in 32 families. The transporters of the
      2HCT family are among the best studied in the class. Here we detect weak sequence
      similarity between the N- and C-terminal halves of the proteins using a sensitive
      method which uses a database containing the N- and C-terminal halves of all the
      sequences in ST3 and involves blast searches of each sequence in the database
      against the whole database. Unrelated families of secondary transporters of the
      same length and composition were used as controls. The sequence similarity
      involved major parts of the N- and C-terminal halves and not just a small
      stretch. The membrane topology of the homologous N- and C-terminal domains was
      deduced from the experimentally determined topology of the members of the 2HCT
      family. The domains consist of five transmembrane segments each and have opposite
      orientations in the membrane. The N terminus of the N-terminal domain is
      extracellular, while the N terminus of the C-terminal domain is cytoplasmic. The
      loops between the fourth and fifth transmembrane segment in each domain are well
      conserved throughout the class and contain a high fraction of residues with small
      side chains, Gly, Ala and Ser. Experimental work on the citrate transporter CitS
      in the 2HCT family indicates that the loops are re-entrant or pore loops. The re
      entrant loops in the N- and C-terminal domains enter the membrane from opposite
      sides (trans-re-entrant loops). The combination of inverted membrane topology and
      trans-re-entrant loops represents a new fold for secondary transporters and
      resembles the structure of aquaporins and models proposed for Na+/Ca2+
      exchangers.

PMID- 15853818
TI  - Mineralocorticoid resistance.
AB  - The mineralocorticoid aldosterone plays a crucial role in regulation of volume
      and electrolyte homeostasis. In recent years there has been considerable progress
      in deciphering the role of aldosterone in human physiology by the study of
      monogenic disorders exhibiting mineralocorticoid resistance. Although these
      disorders are rare, the elucidation of their molecular basis has yielded many
      insights into aldosterone biology that are proving relevant to the care of
      patients with a wide variety of cardiovascular diseases. Recent advances in
      understanding the molecular basis of syndromes of mineralocorticoid resistance
      are reviewed with a view towards an improved understanding of the role of
      aldosterone in renal sodium transport and its relationship to cardiovascular
      disease.

PMID- 15853819
TI  - The effect of combination therapy with propylthiouracil and cholestyramine in the
      treatment of Graves' hyperthyroidism.
AB  - OBJECTIVE: The study aims to evaluate the efficacy of combination therapy with
      propylthiouracil (PTU) and cholestyramine in the treatment of Graves'
      hyperthyroidism. BACKGROUND: Thyroxine (T4) is metabolized mainly in the liver by
      conjugation to glucuronides and sulphates that enter the enterohepatic
      circulation. Thyrotoxic patients have an abnormal increase in thyroid hormone in
      their enterohepatic circulation. Previous studies on combination therapy with
      methimazole and cholestyramine for Graves' hyperthyroidism have shown it to be an
      effective adjunctive treatment. In this study, we examined the efficacy of
      combination therapy with PTU and cholestyramine in the treatment of Graves'
      hyperthyroidism. METHODS: Thirty patients with newly diagnosed Graves'
      hyperthyroidism were randomly divided into two groups: group I (n = 15) received
      PTU 100 mg twice a day, propranolol 40 mg twice a day and cholestyramine 4 g
      twice a day for 4 weeks; group II (n = 15) received PTU 100 mg twice a day and
      propranolol 40 mg twice a day for 4 weeks. The therapeutic efficacy was
      determined by serum total triiodothyronine (TT3), free thyroxine (FT4) and TRAb
      levels at baseline, and at the end of 2 and 4 weeks during the study period.
      RESULTS: There was no significant difference in baseline thyroid function
      parameters. At the end of 2 and 4 weeks of the study period, serum TT3 and FT4
      levels of group I were significantly lower than those of group II. No significant
      differences in the TRAb level were found between the two groups. CONCLUSION:
      Cholestyramine contributed to a more rapid and complete decline in thyroid
      hormone levels in patients with Graves' hyperthyroidism. It was thus proved to be
      an effective and well-tolerated adjunctive therapy.

PMID- 15853820
TI  - Prevalence of hypopituitarism and growth hormone deficiency in adults long-term
      after severe traumatic brain injury.
AB  - OBJECTIVE: Traumatic brain injury (TBI) has been associated with hypopituitarism
      and GH deficiency. However, TBI-mediated hypopituitarism may be more frequent
      than previously thought. The present work, performed in patients with severe TBI
      at least 1 year before, had three aims: (i) to evaluate the prevalence of
      hypopituitarism, (ii) in particular to evaluate the prevalence of GH deficiency,
      and (iii) to compare three different tests of GH reserve in this cohort. DESIGN
      AND PATIENTS: From a nonselected group of 249 patients admitted to our Clinical
      Centre for severe TBI over the last 5 years, 200 of them answered a custom made
      questionnaire of symptoms of hypopituitarism enclosed in the invitation letter to
      participate in the study. A total of 170 (99 men and 14 women), accepted to
      participate in the study (study cohort); 57 had normal questionnaires and were
      not further studied, 14 discontinued the study, and 99 attended the hospital for
      dynamic tests of pituitary hormone deficiencies. From these, 44 subjects with IGF
      I in the lower range were tested with GHRH+GHRP-6; ITT; and glucagon tests of GH
      reserve, on three different occasions. MEASUREMENTS: Pituitary hormones plus IGF
      I and target gland hormones were analysed. RESULTS: With regard to the initial
      cohort of 170 subjects (100%), three (1.7%) showed diabetes insipidus; 10 (5.8%)
      TSH deficiency, 11 (6.4%) ACTH deficiency and 29 (17%) gonadotrophin deficiency.
      In 10 subjects (5.8%), GH deficiency was diagnosed by strict criteria. Finally,
      15 (8.8%) showed combined deficit of several hormones. CONCLUSION: After severe
      head trauma, gonadotrophin deficiency was the most common pituitary deficit. GH
      deficiency showed a prevalence similar to ACTH and TSH deficits, i.e. near 6% of
      the cohort. Taken together, 24.7% of the subjects studied showed any type of
      pituitary hormone deficiency.

PMID- 15853821
TI  - Expression of growth hormone-releasing hormone receptor splicing variants in
      human primary adrenocortical tumours.
AB  - OBJECTIVE: Several splice variants (SVs) of GHRH receptor (GHRH-R) have been
      identified in various human cancers through which GHRH antagonists may exert
      their IGF-II-mediated antiproliferative action. Because the overexpression of the
      IGF-II gene is a frequent feature of adrenal carcinoma, we searched for the
      presence of GHRH-R SVs in these tumours. METHODS AND RESULTS: The expression of
      GHRH-R SVs was assessed by nested PCR in 45 human adrenocortical tumours. We have
      amplified 720-, 566- and 335-bp PCR products only in carcinomas. Their sequence
      revealed three open reading frames, corresponding to SV1, SV2 and SV4 of GHRH-R.
      SV2 was detected in five of 24 cancers examined, whereas the incidence of SV1 and
      SV4 was lower. Their simultaneous expression was observed in one carcinoma. No
      PCR products for SV3 or wild-type GHRH-R were found in carcinomas; mRNA for wild
      type GHRH-R or SVs of GHRH-R were not observed either in adenomas or in normal
      adrenal or in NCI-H295R cells. Interestingly, all carcinomas which expressed SVs
      were also positive for the presence of GHRH mRNA. CONCLUSION: This is the first
      time that the expression of splice variants of GHRH-R has been demonstrated in
      human adrenal carcinoma. This study raises the possibility that splice variants
      might play a role in adrenal carcinogenesis and might offer the possibility for
      new therapeutic strategies at least in a subgroup of adrenal carcinomas.

PMID- 15853822
TI  - Effects of small intestinal and gastric glucose administration on the suppression
      of plasma ghrelin concentrations in healthy older men and women.
AB  - OBJECTIVE: Ghrelin is a peptide hormone secreted primarily from the gastric
      mucosa. It plays a role in energy balance by stimulating appetite, thereby
      increasing food intake and enhancing weight gain and fat mass deposition. Plasma
      ghrelin concentrations increase with fasting and are suppressed by nutrient
      intake. The aim of this study was to examine in humans the relative contributions
      of small intestinal and gastric nutrient exposure to postprandial suppression of
      ghrelin, to determine whether gastric exposure is necessary for ghrelin
      suppression. PATIENTS: Twelve healthy older (age range 65-85 years) men (n = 7)
      and women (n = 5) were studied. DESIGN: On three separate days, equivolaemic (315
      ml) intragastric (IG) and intraduodenal (ID) carbohydrate solutions (both 300
      kcal) or intragastric water (control) were infused over 150 min. MEASUREMENTS:
      Food intake was quantified at a buffet meal offered immediately following each
      150-min infusion. Blood ghrelin, cholecystokinin and glucose concentrations were
      measured. RESULTS: There was a 25% suppression of mean plasma ghrelin
      concentrations following ID glucose (ID 2016 vs. control 2686 ng/l, P < 0.0001)
      and a 19% suppression following IG glucose (IG 2181 vs. control 2686 ng/l, P <
      0.0001), with ghrelin concentrations slightly (7.6%) and nonsignificantly lower
      after ID than after IG glucose infusions (P = 0.2). There was no difference
      between the treatments for the amount of food consumed at the buffet meal (P =
      0.88). CONCLUSIONS: Although the primary source of ghrelin is the gastric mucosa,
      these results suggest that small intestinal nutrient exposure is sufficient for
      food-induced plasma ghrelin suppression in humans, and that gastric nutrient
      exposure is not necessary for suppression.

PMID- 15853823
TI  - Novel mutations in epithelial sodium channel (ENaC) subunit genes and phenotypic
      expression of multisystem pseudohypoaldosteronism.
AB  - OBJECTIVES: Multisystem pseudohypoaldosteronism (PHA) is a rare autosomal
      recessive aldosterone unresponsiveness syndrome that results from mutations in
      the genes encoding epithelial sodium channel (ENaC) subunits alpha, beta and
      gamma. In this study we examined three PHA patients to identify mutations
      responsible for PHA with different clinical presentations. PATIENTS: All three
      patients presented uniformly with symptoms of severe salt-loss during the first
      week of life and were hospitalized for up to a year. Beyond infancy, one of the
      patients showed mild renal salt loss and had no lower respiratory tract
      infections until 8 years of age, while the other patients continue with a severe
      course. RESULTS: We sequenced the complete coding regions and intron-exon
      junctions of the genes encoding alpha, beta and gamma subunits of ENaC for all
      patients. The results revealed that the mild case represents a novel compound
      heterozygote including a missense (Gly327Cys) mutation in the alphaENaC gene.
      Sequences of relatives over three generations confirmed that the missense
      mutation co-segregates with PHA. This mutation was not found in 60 control
      subjects. The other patients with severe PHA had two homozygous mutations, a
      novel deletion mutation in exon 8 of the alphaENaC gene and a splice site
      mutation in intron 12 of the betaENaC gene. Most of the PHA-causing mutations
      appear in the alphaENaC gene located on chromosome 12 rather than in the beta and
      gammaENaC genes located tandemly on chromosome 16. However, the frequency of
      sequence variants in patients and control subjects showed no difference between
      genes. CONCLUSIONS: Severe PHA cases are associated with mutations leading to
      absence of normal-length alpha, beta or gammaENaC, while a mild case has been
      found to be associated with a missense mutation in alphaENaC. The predominance of
      PHA-causing mutations in the alphaENaC gene may be related to the function of
      this subunit.

PMID- 15853824
TI  - Ghrelin and its relationship to growth hormones during normal pregnancy.
AB  - OBJECTIVE: Ghrelin and GH secretagogue receptors have been found in reproductive
      organs, including the placenta. The physiology of ghrelin in pregnancy has not
      been explored. In human pregnancy, pituitary GH is gradually replaced by
      placental GH (PGH). The present study was undertaken to examine serum ghrelin
      levels during normal pregnancy and to determine to what extent changes in ghrelin
      levels coincide with changes in serum levels of free and total GH and PGH. Design
      Prospective study with blood sampling from pregnant women in gestational weeks 8,
      18, 26 and 36 and postpartum. PATIENTS: Eleven nondiabetic pregnant women with
      singleton pregnancies. MEASUREMENTS: Serum ghrelin was determined using an in
      house radioimmunoassay. Serum PGH was determined in a solid-phase
      immunoradiometric assay, serum GH and insulin in a time-resolved
      immunofluorometric assay, and serum GHBP in an in-house immunofunctional assay.
      RESULTS: Serum ghrelin levels peaked in week 18 (1.20 +/- 0.09 microg/l) and the
      lowest levels were observed in late third trimester (0.87 +/- 0.06 microg/l),
      corresponding to a mean decrease of 27.7% (P < 0.001) from peak levels. An
      increase was observed again postpartum. Serum GH diminished throughout pregnancy
      to low third-trimester values (0.12 +/- 0.03 microg/l; P < 0.001), and PGH
      increased to 25.7 +/- 2.86 microg/l (P < 0.001) in week 36. Neither total nor
      calculated free levels of growth hormones correlated to ghrelin levels, and no
      significant correlations were observed between ghrelin and maternal body mass
      index (BMI) or fasting insulin levels. CONCLUSIONS: Serum ghrelin levels peak
      around mid-gestation in human pregnancy. Ghrelin levels during pregnancy are at
      their lowest in the third trimester at a time of increased body weight,
      development of insulin resistance and high serum levels of PGH. However, no
      associations were observed between ghrelin and the two growth hormones.

PMID- 15853825
TI  - A retrospective study of growth hormone use in adolescents with cystic fibrosis.
AB  - OBJECTIVES: Studies of growth hormone (GH) effectiveness in prepubertal children
      with cystic fibrosis (CF) have been published previously. We present a
      retrospective study of GH treatment in adolescents with CF. STUDY DESIGN: We
      performed a retrospective evaluation of data from 25 pubertal adolescents (ages
      13 years 4 months to 16 years 11 months, Tanner stage III or IV). Thirteen (4 F)
      were followed for 1 year, then received 1 year of treatment with GH (GHTX). We
      compared the results with a 'control' group of 12 (4 F) whose growth was followed
      for 1 year (NonTX) but who were not treated with GH at the time of this review.
      Anthropometric data included: height, weight, lean tissue mass (LTM) and bone
      mineral content (BMC). Pulmonary function, number of hospitalizations,
      glycosylated haemoglobin (HbA1c), random blood glucose levels, IGF-I, oestradiol
      and testosterone levels are also reported. RESULTS: There was no difference
      between the groups at baseline. After 1 year, GHTX had significantly greater
      height and weight velocity, height and weight Z-scores, body mass index (BMI),
      LTM and BMC. Absolute pulmonary function was better and hospitalizations were
      fewer in the GHTX. No subject developed glucose intolerance or had any other side
      effects. CONCLUSION: These results suggest that GH use in pubertal adolescents
      with CF safely improves height, body weight, bone mineralization and clinical
      status.

PMID- 15853826
TI  - Adiponectin, acylation stimulating protein and complement C3 are altered in
      obesity in very young children.
AB  - OBJECTIVE: Childhood obesity is increasing worldwide. This, in turn, is
      associated with chronic disease risk factors including hyperlipidaemia. The aim
      of the present study was to examine adiponectin, acylation-stimulating protein
      (ASP) and its precursor, complement C3, in very young obese and nonobese children
      and the corresponding associations with plasma lipid and lipoproteins. All three
      adipose tissue secreted factors are involved in fat metabolism, and little is
      known of the levels in very young children. DESIGN AND METHODS: A total of 124
      healthy children from 2 to 6 years old were evaluated for weight, height, plasma
      lipids and adipokines. Based on percentage ideal body weight (%IBW), 60 children
      were nonobese and 64 were overweight/obese. RESULTS: ASP and C3 were
      significantly increased (P = 0.0002 and P < 0.0001, respectively) in obese vs.
      nonobese, and this pattern held true when separated in three age groups: toddler
      (2-3 years), preschool (4-5 years) and primary school (6 years). By contrast,
      adiponectin was significantly decreased (P = 0.04). When separated based on a
      positive family history of obesity, ASP was increased (P = 0.005). Other than a
      small (23.4%) increase in plasma triglyceride, all other lipids [cholesterol, low
      density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol
      and nonesterified fatty acids] were normal. ASP, C3 and adiponectin were strongly
      correlated with %IBW (r = 0.515, P < 0.0001; r = 0.383, P < 0.0001; r = -0.211, P
      = 0.03, respectively). CONCLUSIONS: Changes in plasma adipokines are seen in very
      young obese children in the absence of lipid changes. These changes in ASP, C3
      and adiponectin in very young obese children may predispose towards enhanced fat
      storage (ASP) and decreased fat oxidation (adiponectin) further driving the
      obesity profile.

PMID- 15853827
TI  - The peroxisome proliferator activated receptor gamma Pro12Ala polymorphism is
      associated with a lower hirsutism score and increased insulin sensitivity in
      women with polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism
      and chronic anovulation. The genetic background of the insulin resistance
      frequently associated with PCOS is unclear. OBJECTIVES: To examine the influe nce
      of the Pro12Ala polymorphism of the peroxisome proliferator activated receptor
      gamma (PPARgamma), which is thought to play a role in the regulation of insulin
      sensitivity, on endocrine and metabolic parameters in PCOS patients. METHODS:
      PPARgamma alleles were analysed in 102 PCOS patients (age 27 +/- 5.3 years) and
      104 age matched control women. PCOS was defined by the NIH-criteria as the
      presence of chronic oligo- or anovulation and hyperandrogenism. Family history
      and clinical parameters were evaluated by personal interview and physical
      examination, parameters of insulin resistance [homeostasis model assessment
      (HOMA) and Matsuda-index] were evaluated with a glucose tolerance test. RESULTS:
      Seventy-nine (77.5%) PCOS patients were carriers of the wild-type PPARgamma
      allele (Pro/Pro), while 23 (22.5%) had at least one Ala allele (X/Ala), with an
      equal distribution in controls. X/Ala PCOS women were more insulin-sensitive,
      evidenced by lower fasting insulin, HOMA index and insulin secretion. Differences
      in insulin resistance did not depend on body mass index. The genotype had no
      influence on lipid status, leptin, adiponectin, ghrelin, or family history of
      type 2 diabetes. A significantly lower proportion of Pro/Ala patients had
      hirsutism and they had on average lower hirsutism scores than Pro/Pro patients.
      No relationship was found between the Pro/Ala polymorphism and other signs of
      hyperandrogenism. CONCLUSION: The Pro12Ala polymorphism of the PPARgamma gene is
      associated with increased insulin sensitivity and lower hirsutism scores in PCOS
      women.

PMID- 15853828
TI  - Are thyroid peroxidase antibodies associated with cardiovascular disease risk in
      patients with subclinical hypothyroidism?
AB  - OBJECTIVE: Conflicting evidence has been reported about whether subclinical
      hypothyroidism (SCH) is associated with hyperlipidemia or cardiovascular disease.
      Thyroid peroxidase antibodies (TPOAb) are more common in persons with SCH. The
      purpose of this study was to evaluate whether the presence of (TPOAb) in people
      with SCH is associated with markers of cardiovascular disease. DESIGN: Cross
      sectional study using multivariate regression. PATIENTS: Adults over age 40 who,
      in the National Health and Nutrition Examination Survey (NHANES) III, met the
      criteria for SCH (n = 188). MEASUREMENTS: Participants were stratified into TPOAb
      negative (n = 82) and TPOAb-positive (n = 106) groups. Markers of cardiovascular
      disease risk were compared between the TPOAb-negative and TPOAb-positive groups.
      Multivariate regression models were performed to adjust for potential
      confounders. RESULTS: In bivariate analyses, individuals with and without TPOAb
      had similar levels of triglycerides, high-density lipoprotein, low-density
      lipoprotein, total cholesterol and C-reactive protein. Homocysteine levels were
      higher in the patients without antibodies (P = 0.01). After adjusting for, age,
      gender, smoking, hypertension, diabetes and use of a lipid-lowering medication,
      however, no statistically significant relationships were found between the
      presence of TPOAb and any of the cardiovascular risk markers. CONCLUSIONS: The
      presence of thyroid peroxidase antibodies does not appear to correlate with
      cardiovascular disease risk in patients with subclinical hypothyroidism. This
      study does not support the measurement of TPOAb antibodies in SCH as a strategy
      for guiding treatment or assessment of cardiovascular disease risk.

PMID- 15853829
TI  - Arg16Gly polymorphism in beta2-adrenergic receptor gene is not associated with
      thyrotoxic periodic paralysis in Korean male patients with Graves' disease.
AB  - BACKGROUND: Thyrotoxic periodic paralysis (TPP) occurs most frequently in Asian
      males and present with an acute episode of proximal muscle weakness in the
      setting of thyrotoxicosis. Despite the fact that mutations were described in
      genes encoding ion channels in familial hypokalaemic periodic paralysis, no
      definite genetic variants were found in TPP. beta2-adrenergic receptors (ADRB2s)
      are expressed in skeletal muscle and stimulate the sodium pump. Single nucleotide
      polymorphisms in ADRB2 gene were identified and may act as disease modifiers in
      various diseases. OBJECTIVE: We were to demonstrate that ADRB2 gene might be a
      susceptibility gene for TPP in Korean male patients with Graves' disease. DESIGN
      AND PATIENTS: In a series of 28 male TPP patients and 31 control patients, three
      polymorphisms in ADRB2 gene have been studied: a T to C substitution at -47 (
      47T/C), Arg16Gly and Gln27Glu. Control patients were male Graves' patients
      without history of paralysis. RESULTS: The distributions of the -47C, Gly16 and
      Glu27 alleles in all patients were 0.02, 0.34 and 0.02, respectively. The
      genotype Arg16/Arg16 was not significantly associated with TPP (odds ratio 0.53;
      95% confidence interval, 0.19-1.50; corrected P = 0.897). Also, the frequency of
      genotype Gly16/Gly16 was not significantly different in TPP patients than in
      controls (0.07 vs. 0.23; odds ratio, 0.26; 95% confidence interval, 0.05-1.40;
      corrected P = 0.45). Allele frequencies of ADRB2 in patients with TPP did not
      differ from controls. CONCLUSIONS: The polymorphism of the ADRB2 gene may not
      confer genetic susceptibility to TPP in Korean male patients with Graves'
      disease.

PMID- 15853830
TI  - Improvement of intrinsic myocardial contractility and cardiac fibrosis degree in
      acromegalic patients treated with somatostatin analogues: a prospective study.
AB  - BACKGROUND: Acromegalic patients have increased left ventricular (LV) mass (M)
      and impaired diastolic function. AIM: Using ultrasonic cardiac tissue
      characterization, we evaluated the early changes in cardiac fibrosis (IBS) and
      intrinsic myocardial contractility (CVI) as well as their reversibility after
      treatment with somatostatin analogues (SMSA) in patients with acromegaly.
      PATIENTS AND METHODS: Twenty-two acromegalic patients with active untreated
      disease (Acro(UNTR)) underwent conventional Doppler echocardiography and
      integrated backscattering; 25 healthy subjects (controls) and eight patients with
      acromegaly in remission after pituitary adenomectomy (Acro(REM)) served as
      controls. RESULTS: As expected, Acro(UNTR) at baseline had higher LVM than
      controls or Acro(REM) (P < 0.001); LVM reduced in acromegalic patients after SMSA
      (P < 0.005 vs. baseline) while LV ejection fraction did not change. LV diastolic
      function was reduced in all acromegalic patients, either at baseline or after
      SMSA therapy (E/A ratio, 0.96 +/- 0.3 and 1.1 +/- 0.3, respectively, P < 0.002
      vs. controls, 1.6 +/- 0.3). CVI was reduced in Acro(UNTR) (14.3 +/- 5.8%, P <
      0.003 vs. controls, 28.7 +/- 7.5%) and greatly improved after SMSA (22.5 +/-
      4.5%, P < 0.003 vs. baseline). Cardiac fibrosis was increased in Acro(UNTR)
      (IBS(MSI), 53.7 +/- 5.3%P < 0.002 vs. controls) and reduced after SMSA (43.7 +/-
      4.2%P < 0.002 vs. baseline) albeit not reaching values observed in controls. More
      importantly, five of 22 (23%) Acro(UNTR) patients had normal LVM, but increased
      cardiac fibrosis as revealed by back scattering. IBS values and CVI% were related
      with serum GH and IGF-1 (P < 0.0001) levels, and the estimated duration of
      disease (P < 0.005). CONCLUSIONS: The present study demonstrated that active
      acromegalic patients had early impairment of systolic function and increased
      cardiac fibrosis; increased fibrosis may precede LV hypertrophy; these changes
      are related to the activity of disease and might improve during treatment with
      SMSA.

PMID- 15853831
TI  - Evaluation of GH reserve in patients with adrenal incidentalomas and biochemical
      evidence of subclinical autonomous glucocorticoid hypersecretion.
AB  - OBJECTIVE: Although it is well established that overt hypercortisolism in
      patients with active Cushing's syndrome leads to a profound suppression of
      stimulated GH secretion, the role of subclinical autonomous glucocorticoid
      hypersecretion (SAGH), currently detected with increasing frequency in patients
      with adrenal incidentalomas, on GH secretory reserve has received little
      attention. The aim of the present study was to evaluate whether SAGH in patients
      presented with adrenal incidentalomas has a negative effect on GH secretory
      reserve. DESIGN AND PATIENTS: Sixteen patients with overt Cushing's syndrome (CS)
      and 36 patients with adrenal incidentalomas were investigated. The latter group
      was further divided in 23 patients who demonstrated an adequate suppression of
      cortisol levels (of < 70 nmol/l) following the low-dose dexamethasone suppression
      test (LDDST) and in 13 patients, who failed to suppress (cortisol levels post
      LDDST > 70 nmol/l). The former group was defined as normocortisolaemic (NC) and
      the latter group as representing patients with SAGH. The combined pyridostigmine
      + GHRH test (PD + GHRH) was used to assess the GH secretory reserve of these
      patients. RESULTS: Peak GH levels following PD + GHRH administration were
      significantly lower in CS patients compared to both the NC and SAGH group of
      patients with adrenal incidentalomas (2.2 +/- 0.7 vs. 18.9 +/- 2.6 and 21.5 +/-
      3.6 microg/l, respectively, P < 0.05); no difference was observed in peak GH
      responses between the NC and SAGH group of patients. A subnormal GH response
      (defined as GH(max) < 12.8 microg/l) was observed in all 16 patients with CS.
      However, only seven NC and three SAGH patients failed to respond adequately.
      Correlation analysis revealed a negative correlation between peak GH response to
      PD + GHRH and plasma cortisol concentrations in CS patients (R =-0.6, P = 0.012),
      while in patients with adrenal incidentalomas such a correlation was absent.
      Contrary to patients with CS in whom body mass index (BMI) was not correlated to
      peak GH, a significant negative correlation between peak GH response to PD + GHRH
      and BMI was disclosed in patients with adrenal incidentalomas (R =-0.49, P =
      0.003). In these patients, again contrary to CS patients, a significant negative
      correlation was also found between peak GH post PD + GHRH and age (R = -0.46, P =
      0.002). CONCLUSIONS: In conclusion, our results provide evidence that, contrary
      to patients with overt CS, SAGH does not affect the GH secretory response to
      provocative stimulation.

PMID- 15853832
TI  - Mutational analysis of PPARG as a candidate tumour suppressor gene in
      enteropancreatic endocrine tumours.
AB  - OBJECTIVES: Loss of heterozygosity (LOH) or deletion of chromosome 3p is a
      frequent finding in enteropancreatic endocrine tumours (EPETs), suggesting the
      pathogenetic involvement of one or more tumour suppressor genes on 3p. PPARG, the
      gene encoding the gamma isoform of the peroxisome proliferator-activated receptor
      (PPARgamma), is highly expressed in normal human pancreatic islet cells, is
      located at 3p25, and has been reported to sustain loss-of-function mutations in
      human colorectal carcinomas. Additionally, the development of islet cell
      hyperplasia in an islet cell-specific pparg knockout mouse has further emphasized
      the attractiveness of PPARG as a candidate gene important in the pathogenesis of
      EPETs. Therefore, we sought to examine PPARG for intragenic inactivating
      mutations, the evidence needed to rigorously establish it as a tumour suppressor
      in EPETs. PATIENTS AND DESIGN: Twenty-three EPETs from 20 patients were examined
      for coding region mutations in PPARG and for LOH on 3p at microsatellite markers
      flanking PPARG. RESULTS: LOH on 3p was detected in tumours from six patients
      (30%), but no intragenic mutations were detected in PPARG, whether or not LOH was
      present. CONCLUSION: These findings strongly suggest that PPARG does not commonly
      function as a classical tumour suppressor gene in the pathogenesis of EPETs.

PMID- 15853833
TI  - The effect of plasminogen activator inhibitor-1 gene 4G/5G polymorphism on
      glucose and lipid metabolisms in Turkish obese children.
AB  - OBJECTIVE: Obesity is a metabolic disorder that is associated with increased
      plasminogen activator inhibitor-1 (PAI-1) concentration in the circulation. This
      increase is related to insulin resistance, dyslipidaemia and cardiovascular
      disease. Some studies have demonstrated a relationship between plasma PAI-1
      concentrations and the 4G/5G gene polymorphism in the PAI-1 gene, while other
      studies have not. It is well known that plasma PAI-1 levels are increased in
      obesity; however, the relationship between the polymorphism and obesity remains
      unclear. In this study, we aimed to elucidate the effect of the PAI-1 4G/5G
      polymorphism on glucose and lipid metabolism parameters in Turkish obese
      children. DESIGN AND PATIENTS: Ninety children with obesity (37 male, 53 female;
      mean age 11.1 +/- 3.4 years; range 5.8-17.6 years) were included in the study.
      The children were divided into three groups according to the PAI-1 promoter 4G/5G
      polymorphism (4G/4G, 4G/5G and 5G/5G). These groups were compared for age, body
      mass index (BMI), serum glucose, lipid and insulin levels, and homeostasis model
      assessment of insulin resistance (HOMA-IR) score. RESULTS: The genotype
      distribution was 52% (47/90) 4G/4G, 25% (22/90) 4G/5G and 23% (21/90) 5G/5G. No
      statistically significant differences among genotype groups were found with
      respect to age, BMI, serum levels of glucose, lipid and insulin, and HOMA-IR
      score. CONCLUSION: Although the frequency of the 4G/4G genotype was higher in
      subjects in the current study than in subjects reported in the literature, in our
      study group we observed no influence of the PAI-1 4G/4G polymorphism on lipid and
      glucose metabolism.

PMID- 15853834
TI  - Glycodelin responses to hyperinsulinaemic clamp vary according to basal serum
      glycodelin concentration.
AB  - OBJECTIVE: Treatment with metformin, an insulin-lowering agent, increases serum
      glycodelin, a progesterone-regulated lipocalin protein of the reproductive axis
      that may play a role in foeto-maternal defence mechanisms. This finding led to
      the hypothesis that insulin might decrease serum glycodelin concentration.
      DESIGN, PATIENTS AND MEASUREMENTS: Euglycaemic hyperinsulinaemic clamp
      experiments (n = 50) were carried out on 28 women of reproductive age (range 25
      47 years; mean +/- SEM 39 +/- 1.0 years), and the results were analysed with
      respect to their baseline serum progesterone (< 10 or > or = 10 nmol/l) and
      glycodelin (< 10 or > or = 10 microg/l, equivalent to < 357 or > or = 357 pmol/l)
      concentrations at the onset of the clamp. Ten clamp experiments were performed on
      five women wearing a levonorgestrel-releasing intrauterine device (IUD), and
      these were analysed as a separate group. RESULTS: Contrary to the hypothesis, no
      acute glycodelin-lowering effect of insulin was found in any of the groups
      studied. All the small rises in glycodelin levels detected during acute
      hyperinsulinaemia occurred in the comparisons of medians and not means, and all
      such changes took place within the limits seen in the women with no progesterone
      exposure. In the group with low progesterone/low glycodelin (n = 21), glycodelin
      showed a small but significant increase at 30 and 90 min of the clamp (P < 0.01).
      In the group with elevated progesterone/low glycodelin (n = 11), there was a
      slight glycodelin increase at 30 min (P < 0.05), whereas no increase was found in
      the group with elevated glycodelin levels (n = 8). In the clamp experiments on
      women with levonorgestrel-releasing IUD, the basal glycodelin level was low in
      all cases and, as in the other women with low glycodelin levels, glycodelin was
      slightly increased at 30, 60 and 90 min of hyperinsulinaemia (P < 0.01).
      CONCLUSIONS: The results rule out any acute glycodelin-reducing effects of
      insulin, although indirect long-term effects mediated by insulin on glycodelin
      secretion cannot be excluded.

PMID- 15853835
TI  - Effect of growth hormone and 17beta-oestradiol treatment on metabolism and body
      composition in girls with Turner syndrome.
AB  - OBJECTIVE: Girls with Turner syndrome (TS) receive GH treatment during childhood,
      and in adolescence this treatment may be combined with oestradiol. We have
      studied the effects of this combined treatment on metabolism and body
      composition. MATERIAL AND METHODS: We performed a double-blind, placebo
      controlled, randomized, crossover study. All girls with TS (n = 8, 16 +/- 2
      years) were treated with placebo + placebo, GH + placebo or GH + 17beta
      oestradiol for 2 months, and were studied at the end of each period. Controls (n
      = 10, 14 +/- 2 years) were studied once without treatment. Twenty-four-hour
      sampling of oestradiol, growth factors, insulin, glucose, lipolytic and
      gluconeogenic precursors was performed, followed by an oral glucose tolerance
      test (OGTT) and assessment of body composition and mineral content. RESULTS: GH
      induced insulin resistance, which was not aggravated further by concomitant
      oestradiol treatment. The 24-h integrated serum 17beta-oestradiol was reduced
      compared to controls (0.58 +/- 0.32 vs. 2.81 +/- 2.78 nmol/l/24 h, P = 0.032),
      but increased during GH + oestrogen (E2) treatment without reaching control
      levels, while GH + placebo caused a further reduction (anova, P = 0.008). Total
      fat mass was increased in girls with TS compared with controls (P = 0.009), while
      lean body mass (P = 0.02) and bone mineral content (P = 0.04) was decreased, with
      specific regional characteristics in body composition. CONCLUSION: GH treatment
      induces insulin resistance and changes in body composition in TS, which is not
      further compromised by concomitant oestradiol treatment. Body composition is
      changed in TS, with specific regional changes, in comparison with controls.
      Integrated 24-h oestradiol is low in TS, and is only partially restored during
      treatment with standard doses of 17beta-oestradiol.

PMID- 15853836
TI  - A new sustained-release preparation of human growth hormone and its
      pharmacokinetic, pharmacodynamic and safety profile.
AB  - OBJECTIVE: Adult GH replacement is currently given by daily subcutaneous (sc)
      injections. Recently, sustained-release (SR) preparations of GH have been
      developed, the preparations being characterized by a dominant early release,
      resulting in supraphysiological early GH peaks, and a rapid decline thereafter.
      We present data on a new SR GH preparation. DESIGN: Phase I/II study of hGH
      Biosphere(R) (SkyePharma AB, Malmo, Sweden), a new SR preparation of recombinant
      human GH in amylopectin microspheres coated with polylactide-coglycolide.
      PATIENTS: Eight adults with severe, untreated GH deficiency (stimulated GH peaks
      between < 1 and 1.7 microg/l), aged 36.1 years (range 22-49 years) in good
      general health. MEASUREMENTS: Pharmacokinetic (PK), pharmacodynamic (PD) and
      safety data over a period of 28 days. RESULTS: The systemic and local
      tolerability of the drug was satisfactory, and no serious adverse events
      occurred. PK analysis showed a smaller early serum hGH peak followed by a broad
      sustained second peak of hGH (C(max) 1.20 microg/l at 7.2 days), and hGH levels
      were maintained above baseline for at least 14 days. The mean GH level never
      exceeded 1.1 microg/l, making the GH fluctuations comparable to continuous sc
      infusion. Resultant IGF-I concentrations were characterized by sustained
      elevation at a level near C(max) of 103 microg/l (at t(max) of 9.7 days), equal
      to an SD score of +0.8. IGF-I generation per administered GH was more efficient
      compared with reports of other SR preparations. CONCLUSION: hGH-Biosphere(R) is a
      well-tolerated SR GH preparation with superior efficacy in achieving target IGF-I
      levels without causing supraphysiological GH concentrations. Our data suggest the
      suitability of this preparation for longer-term trials in adults with injection
      frequencies of no more than once every 2-3 weeks.

PMID- 15853837
TI  - Growth hormone releasing hormone plus arginine stimulation testing in young
      adults treated in childhood with cranio-spinal radiation therapy.
AB  - OBJECTIVE: Growth hormone deficiency (GHD) secondary to cranio-spinal radiation
      therapy (CSRT) is a complication seen in medulloblastoma survivors. The standard
      for diagnosis of adult GHD is a peak GH < 3 microg/l by the insulin tolerance
      test (ITT). However, insulin tolerance testing exposes patients to the risks of
      hypoglycaemia. Recent studies suggest that the GH releasing hormone + arginine
      (GHRH + ARG) test can identify GHD in cranially irradiated patients at longer
      time intervals after radiation. We evaluated the GHRH + ARG stimulation test
      compared to the ITT in young adults diagnosed with medulloblastoma during
      childhood. PATIENTS: We evaluated 10 young adult patients (age range 17-26 years)
      who were treated with CSRT during childhood for medulloblastoma, and who had
      resultant childhood-onset GHD. MEASUREMENTS: Subjects underwent GH provocative
      testing with the ITT and the GHRH + ARG test. IGF-I and IGFBP3 levels were also
      measured at baseline. RESULTS: Insulin tolerance testing and GHRH + arginine
      stimulation were performed at a mean +/- SD 14 +/- 4.4 years after cranial
      radiation. All patients failed the ITT with median peak GH 0.40 microg/l (range <
      0.05-2.2). GHRH + arginine gave higher peak GH levels with a mean of 7.9 +/- 5.7
      microg/l (P = 0.003). Four patients had peak GH > 9 microg/l and were between 7.8
      and 19.6 years from cranial radiation. There was no correlation of peak GH levels
      with time interval since CSRT. Thirty-three per cent of subjects had normal IGF
      I; neither IGF-I nor IGFBP3 standard deviation scores (SDS) correlated with ITT
      results. CONCLUSIONS: Using a GHRH + arginine cut-off for GHD of 9 microg/l, four
      patients would have been misclassified as GH sufficient, despite being > 7 years
      (with two patients being nearly 20 years) out from CSRT. These findings suggest
      that the pituitary GH-producing cells of young adults continue to maintain
      responsiveness to GHRH + arginine more than 5-10 years after cranial irradiation.

PMID- 15853838
TI  - Use of the Significant Caries Index in quantifying the changes in caries in
      Switzerland from 1964 to 2000.
AB  - OBJECTIVES: To follow the changes in the Significant Caries Index (SiC) and the
      DMFT during the period 1964-2000 in children aged 12 and 15 in the Canton of
      Zurich. METHODS: Examinations of random samples of children in 16 communities of
      the Canton were repeated every 4 years from 1964 onwards using the same standards
      for diagnosing caries. RESULTS: In the 12-year-olds, the children in the low
      tertile had virtually no DMF-experience from 1980 on. On the contrary, the SiC,
      based on the children in the highest tertile, decreased until 1996. At the age of
      15, the zero-average in the low tertile was reached in 1992 but the SiC continued
      to decrease until 2000. In the 12-year age group the reduction of the SiC from
      1964 to 1996 was 81.3% and for the overall DMFT it was 89.7%. The corresponding
      reductions for the 15-year-olds, in this case from 1964 to 2000, were 77.0 and
      88.4%, respectively. The DMFT-counts in the total samples had substantially
      higher coefficients of variation than those in the highest tertile. As a
      consequence, the SiC had relatively smaller confidence intervals than the average
      DMFT. CONCLUSIONS: The SiC is a very useful measure of dental caries experience.
      On the basis of the results in the 15-year-old group, the target of an SiC below
      5.0 is proposed. The decline of the SiC demonstrates that even in the high-risk
      children caries experience has been reduced substantially.

PMID- 15853839
TI  - The association between tooth loss and the self-reported intake of selected CVD
      related nutrients and foods among US women.
AB  - OBJECTIVES: Many studies have reported associations between oral health and
      cardiovascular diseases; poor nutritional status due to impaired dentition status
      has been suggested as a mediator. Our objective is to evaluate the associations
      between tooth loss and the self-reported consumption of fruits and vegetables and
      selected CVD-related nutrients. METHODS: A total of 83,104 US women who completed
      a food frequency questionnaire (FFQ) in 1990 and 1994 and reported number of
      natural teeth in 1992, were included in a cross-sectional analysis relating
      dietary intake to number of natural teeth. A longitudinal analysis was also
      conducted to evaluate whether tooth loss in 1990-1992 was associated with change
      in diet between 1990 and 1994. RESULTS: After adjusting for age, total calorie
      intake, smoking and physical activity, edentulous women appeared to have dietary
      intake associated with increased risk for CVD, including significantly higher
      intake of saturated fat, trans fat, cholesterol and vitamin B12, and lower intake
      of polyunsaturated fat, fiber, carotene, vitamin C, vitamin E, vitamin B6,
      folate, potassium, vegetables, fruits, and fruits excluding juices compared with
      women with 25-32 teeth. In the longitudinal analyses, women who lost more teeth
      were more likely to change their diet in ways that would potentially increase
      risk for development of CVD. They also tended to avoid hard foods, such as raw
      carrot, fresh apple or pear. CONCLUSIONS: Women with fewer teeth have unhealthier
      diets such as decreased intake of fruits and vegetables, which could increase CVD
      risk. Diet may partially explain associations between oral health and
      cardiovascular disease.

PMID- 15853840
TI  - Dental trauma and its association with anatomic, behavioral, and social variables
      among fifth and sixth grade schoolchildren in Jerusalem.
AB  - With the decrease in dental caries prevalence, public health should place
      emphasis on other dental diseases. Dental trauma is an irreversible pathology
      which after occurrence is characterized by life-long debilitating effects.
      OBJECTIVES: To measure the prevalence of trauma in anterior permanent teeth among
      children, and to assess the associations with social, behavioral, and orthodontic
      variables. METHODS: A total of 1195 fifth and sixth grade schoolchildren
      participated, representing the general Jewish population of Jerusalem. Trauma,
      incisal overjet and lip competence were measured by two calibrated examiners in
      the schools. Reasons and location of trauma were assessed according to telephone
      interviews with the parents of the children with severe trauma. RESULTS: The
      total prevalence of dental trauma was 29.6%. Severe trauma, at least involving
      the dentine, was found among 13.5% of the children. Severe dental trauma was more
      prevalent among children with an incisal overjet of 4-6 mm (adjusted OR=1.50,
      P=0.049) or more than 7 mm (adjusted OR=2.51, P=0.018); with incompetent lips
      (adjusted OR=2.31, P<0.001), who learned in public religious schools (adjusted
      OR=1.59, P=0.048) and were males (adjusted OR=1.45, P=0.041). The main reason for
      dental trauma in all surroundings was falling, but sports and violence (not at
      orthodox private schools) were also important reasons. CONCLUSIONS: Based upon
      these findings a community effort is being planned and initiated with the aim of
      educating sports teachers, teachers, health personnel, and schoolchildren
      regarding awareness of dental trauma prevention, with emphasis on utilizing mouth
      guards and early orthodontic intervention, when financially possible.

PMID- 15853841
TI  - The role of dentist, practice and patient factors in the provision of dental
      services.
AB  - OBJECTIVES: Service provision varies by dentist, practice and patient factors.
      However, limited subsets of these potential influences on service rates have been
      explored. More comprehensive models could improve our understanding of the
      factors influencing the pattern of care delivered. The aim of this study was to
      examine variation in dental services by dentist (treatment choice, practice
      beliefs, preferences for patients, demographics), practice (type, location, size
      and volume of practice) and patient (visit, demographic, oral health and socio
      economic) characteristics. METHODS: A random sample of Australian dentists was
      surveyed in 1997-98 (response rate=60.3%). Private general practitioners (n=345)
      provided dentist and practice data, and service provision and patient variables
      were collected from a log of a typical clinical day (n=4,115 patients).
      Multivariate negative binomial regression models were fitted for diagnostic,
      preventive, restorative, extraction and prosthodontic services. RESULTS:
      Significant dentist factors included (P<0.05; RR=rate ratio): lower diagnostic
      rates (RR=0.78) for dentists with stronger practice beliefs for giving
      information about cost and treatment options; preventive rates were lower
      (RR=0.74) for male dentists and higher (RR=1.48) for younger dentists aged 20-29
      years; restorative rates were higher (RR=1.27) for dentists that rated patient
      preferences more highly in treatment choice and in the dentist age group 30-39
      years (RR=1.25); extraction rates were lower (RR=0.61) for dentists with stronger
      preferences for patients that would adhere with treatment but higher (RR=1.57)
      for dentists with stronger preferences for sociable patients; and prosthodontic
      rates were lower (RR=0.38) for dentists with stronger preferences for adaptable
      patients who were willing to cooperate when expected to do so. Practice factors
      included: higher preventive (RR=1.28) and prosthodontic rates (RR=2.07) in solo
      practice; higher preventive (RR=1.34) but lower prosthodontic rates (RR=0.42) in
      capital cities; lower diagnostic (RR=0.82) and extraction rates (RR=0.55) in
      practices with fewer other dentists; higher diagnostic (RR=1.33) and extraction
      (RR=1.62) rates but lower restorative rates (RR=0.84) in practices with lower
      patient visits per year. Patient factors included: lower preventive (RR=0.76) but
      higher extraction rates (RR=1.45) for emergency visits; lower extraction rates
      (RR=0.60) for the insured; higher diagnostic rates (RR=1.17) for new patients;
      higher restorative (RR=1.31) but lower prosthodontic rates (RR=0.46) for patients
      with decayed teeth; higher prosthodontic rates (RR=2.14) for those with dentures;
      and lower preventive (RR=0.66), but higher extraction (RR=2.22) and prosthodontic
      rates (RR=1.82) for patients from lower socio-economic status areas. CONCLUSIONS:
      Dental service rates were influenced by large number of small effects from a wide
      range of dentist, practice and patient factors. Socio-economic and geographic
      barriers may need broad policy innovations to be addressed, but factors such as
      insurance and visit type have the potential to be altered to achieve better
      service outcomes and there is scope for research into clinical outcomes to
      improve the knowledge upon which treatment decisions are based.

PMID- 15853842
TI  - The Children's Fear Survey Schedule-Dental Subscale in Japan.
AB  - OBJECTIVES: The aims of this research are to examine the reliability and validity
      of the Japanese version of the Dental Subscale of Children's Fear Survey Schedule
      (CFSS-DS), and to examine the responses of children in the dental setting and in
      the community. METHODS: The CFSS-DS was translated into Japanese and administered
      to three samples. The first sample comprised 134 child patients aged 8-15 years,
      of whom 100 were assigned for test-retest analysis, and the behavior of the
      remaining 34 additional children were rated during their dental appointments, and
      compared with their questionnaire results. A second sample of 532 child patients
      aged 8-15 years, completed the CFSS-DS and also one additional item measuring
      fear of returning to the dentist. A third sample of 1250 school children aged 8
      15 years was surveyed using the CFSS-DS and the additional item measuring fear of
      returning to the dentist. RESULTS: The Japanese version of the CFSS-DS showed
      good internal consistency (alpha=0.91) and test-retest reliability (r=0.90), as
      well as good criterion validity assessed by the relationship with actual child
      behavior (r(s)=0.51). It also showed good construct validity assessed by
      correlation with willingness to return to the dentist. Fear levels were higher in
      the school sample than in the clinic sample (27.7 versus 24.6). Girls reported
      more fear than boys (26.2 versus 23.2 in the clinic sample, and 30.7 versus 24.8
      in the school sample). Injections, choking, having a stranger touch them, and
      drilling were the most common fears. Factor analyses demonstrated a factor
      pattern similar to the results found in other cultures. CONCLUSION: The results
      suggest that the CFSS-DS is reliable and valid and operates in Japan as it does
      in other cultures.

PMID- 15853843
TI  - What do children's global ratings of oral health and well-being measure?
AB  - OBJECTIVES: To explore the constructs children incorporate in the responses to
      global ratings of their oral health (OH) and OH-related overall well-being (OWB).
      METHODS: Data were collected as part of a project to validate the Child
      Perceptions Questionnaire for ages 11-14 (CPQ11-14), a self-report measure of OH
      related quality of life. Its 37 questions are organized in the symptoms,
      functional limitations, emotional and social well-being domains. Children were
      recruited from paediatric dentistry, orthodontic and orofacial dental clinics. To
      identify the CPQ11-14 domain scores and questions predicting the global ratings,
      correlation and multiple regression analyses were used. RESULTS: Of the 123
      children, 22.8% rated their OH as 'Fair/Poor' and 30.1% reported that their OWB
      was affected by their oral/orofacial condition. Positive significant correlations
      were observed between the OH ratings and the CPQ11-14 oral symptoms and emotional
      well-being domains, and between the OWB ratings and all four CPQ11-14 domains.
      The number of the CPQ11-14 questions significantly correlated with the OH and OWB
      ratings were 8 and 19, respectively. Only the symptoms domain entered the model
      for the OH (R2=0.05), while age, functional limitations and emotional well-being
      domains predicted the OWB (R2=0.18). The OH model included three questions
      (R2=0.13) and the OWB model included age and six questions (R2=0.25). In both
      models all but one of the questions came from the emotional and social well-being
      domains. CONCLUSIONS: These findings suggest that children view OH and its impact
      on well-being as multidimensional concepts. Further research, including
      qualitative studies, is needed to better understand the referents children use
      when responding to global ratings and the factors that determine their responses.

PMID- 15853844
TI  - Comparison of radiographic and clinical diagnosis of approximal and occlusal
      dental caries in a young adult population.
AB  - OBJECTIVES: The aims of the study were: (1) to determine if bitewing radiographs
      provided additional diagnostic yield for occlusal and approximal dental caries in
      adults aged between 17 and 30 years of age when compared with a clinical
      examination only, (2) how this translated into the measurement of dental caries
      experience, and (3) to determine the influence of water fluoridation on the
      diagnosis of dental caries in occlusal and approximal surfaces by clinical
      examination alone and by radiographic examination. METHODS: Between November 2002
      and March 2003 a total of 879 subjects aged 17-30 years had a clinical
      examination using visual and tactile criteria. Subsequent to this examination,
      bitewing radiographs were taken and viewed separately and blind. Approximal and
      occlusal surfaces of molars and premolars were examined on the radiographs.
      RESULTS: Between 22.9-32.9% of approximal caries and 75.9-82.9% of occlusal
      caries was detected by clinical examination, while 93.1-97.1% of approximal
      caries and 33.1-42.6% of occlusal caries was detected by radiographic
      examination. In addition, while only 0.97% of clinically sound approximal
      surfaces and 0.83% of clinically sound occlusal surfaces were diagnosed with
      dentine caries on the radiographs, 67.1-77.1% of approximal caries was detected
      by radiographs alone, an additional diagnostic yield of 204-336%. The DS score
      increased 45-46% and the DMFS score increased 6-11% from the clinical examination
      with the addition of the radiographic information (P<0.001). CONCLUSIONS: The
      prevalence of approximal and occlusal caries was underestimated when clinical
      means only were employed. There was a significant increase in DS and DMFS scores
      from the clinical examination only when radiographic information was added across
      all age groups (P<0.001). This study confirms the value of bitewing radiographs
      in caries diagnosis.

PMID- 15853845
TI  - Routine oral examination: differences in characteristics of Dutch general dental
      practitioners related to type of recall interval.
AB  - OBJECTIVES: The aim of this study was to explore differences in behaviour
      (characteristics and opinions) among general dental practitioners (GDPs), using
      either a fixed (Fx) or an individualized recall interval (Iv) between successive
      routine oral examinations (ROEs). METHODS: In the year 2000, data were collected
      by means of a written questionnaire sent to a random stratified sample of 610
      dentists of whom 521 responded, of which 508 (83%) were used for analysis.
      RESULTS: Two groups of GDPs were distinguished based on their answer to the
      question: 'Do you apply for all patients a fixed recall interval between two
      successive ROEs?' Fifty-one per cent of the GDPs (n=257) applied Fxs for all
      patients, generally for a period of 6 months. Ivs were applied by 49% (n=251) of
      GDPs, depending on the determination of specific patient characteristics.
      Logistic regression analysis showed that GDPs applying Fxs also used fixed
      periods between successive bitewing radiographs for all patients. Furthermore,
      dentists applying Ivs required more time to conduct an ROE, partly because of a
      more extensive periodontal screening. GDPs applying Fxs, adhered more to the
      opinion that a fixed recall regime (every 6 months, as existed before 1995)
      should be re-introduced, whereas the GDPs in support of Ivs were more in favour
      to support the opinion that the ROE is 'an excellent instrument for effective,
      individualized oral care'. CONCLUSIONS: Dutch GDPs differ in the way they deal
      with the determination of recall interval frequency. These are also specific
      differences in performance and opinions regarding ROE. With the changing
      prevalence of oral diseases and the skewed distribution within populations,
      further research is advocated on consistent decision making to determine the most
      appropriate recall policy in preventing oral disease.

PMID- 15853846
TI  - A follow-up study of patients with subjective symptoms related to dental
      materials.
AB  - OBJECTIVES: The extent to which substances released from dental materials cause
      adverse health effects and whether removal of dental materials results in
      improvement of health is a matter of dispute. The aim of the study was to
      investigate changes in the intensity of subjective symptoms after replacement of
      dental materials in patients referred for adverse reactions related to dental
      materials, and to compare the profiles of symptoms with those found in the
      general population. METHODS: Information was obtained from 142 patients referred
      to the Dental Biomaterials Adverse Reaction Unit in Bergen, Norway. At the time
      of examination, all patients completed a questionnaire regarding a range of
      subjective symptoms. A follow-up questionnaire was sent to all patients 1 to 2
      years later. Similar questionnaires were sent to a reference group of 800 persons
      drawn from the general population. RESULTS: The follow-up questionnaires were
      completed and returned by 84 patients, and 441 persons in the reference group.
      The patient group presented higher symptom indices than the reference group
      (P<0.001). Generally, there was some decrease in the intensity of different
      symptoms in patients who had replaced dental materials. The decrease was evident
      regarding intraoral symptoms (P=0.022) and total symptom index (P=0.041). The
      group of patients who had replaced materials still had significantly higher
      symptom indices than those of the reference group. Patients who had not replaced
      dental materials did not present any reduction in symptom indices. CONCLUSION:
      The pattern of symptoms was similar for the groups investigated. At the group
      level, the intensity of local and some general subjective symptoms was reduced
      after replacement of the materials, but not to the level found in the general
      population.

PMID- 15853847
TI  - Letter to the editor.

PMID- 15853849
TI  - Case reports.

PMID- 15853850
TI  - Aortic valve 'sclerosis': a clinically useful marker in coronary disease?

PMID- 15853851
TI  - The role of percutaneous drainage in the modern management of pancreatic
      pseudocysts.

PMID- 15853852
TI  - Asthma and COPD: differences and similarities. With special reference to the
      usefulness of budesonide/formoterol in a single inhaler (Symbicort) in both
      diseases.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) both have a high
      prevalence worldwide and yet each condition remains underdiagnosed. Despite a
      number of common features, these inflammatory respiratory syndromes have distinct
      clinical outcomes. COPD represents a greater economic burden than asthma because
      it has a less favourable prognosis and is associated with greater morbidity and
      mortality. Therefore, it is important to distinguish between these two diseases
      at an early stage, so that appropriate therapy can be prescribed to prevent
      deterioration. However, effective treatments that may be used in both conditions
      can minimise the effects of misdiagnosis and maximise the impact of treatment
      without the associated complexity when both conditions occur together. The
      current review summarises the differences and similarities of asthma and COPD, in
      terms of risk factors, pathophysiology, symptoms and diagnosis, to provide
      greater understanding of the role of budesonide/formoterol in a single inhaler in
      both diseases.

PMID- 15853853
TI  - Schizophrenia syndromes associated with changes in ventricle-to-brain ratios: a
      serial high-resolution three-dimensional magnetic resonance imaging study in
      first-episode schizophrenia patients using subvoxel registration and
      semiautomated quantification.
AB  - A cohort of patients with first-episode schizophrenia was dichotomised into two
      age- and sex-matched groups of clinical syndromes, the active and withdrawn, and
      underwent high-resolution three-dimensional magnetic resonance imaging at
      baseline and 8 months later. A cohort of age- and sex-matched normal controls was
      also imaged at the same time intervals. The application of subvoxel registration
      and semiautomated quantification techniques demonstrated a significantly
      different outcome in ventricular changes between the two groups of patients.
      Compared with the controls, the withdrawn patients showed progressive ventricular
      enlargement, with an increase in ventricle-to-brain volume ratio, whereas the
      active group showed a reduction in ventricle-to-brain volume ratio, with a change
      opposite in sign and smaller in magnitude. These findings lend further support
      for the aetiological validity of this syndromal model of schizophrenia and are
      likely to be of importance in furthering our understanding of its pathogenesis
      and in the development of suitable therapeutic strategies.

PMID- 15853854
TI  - What do patients with chronic rhinitis do with their disease?
AB  - There are numerous patients suffering from chronic rhinitis. What kind of doctors
      do they consult? What are their symptoms? What kind of examinations do they do?
      What kind of medication do they use? Are they ever treated surgically? The
      objective of this study was to give answers to such questions. This is a study of
      269 patients suffering from chronic rhinitis aged from 3 to 72 years. Of the 269
      patients, 198 had already visited another physician before consulting us. The
      most common symptom was nasal obstruction. The most commonly used oral medication
      was antihistamines, whereas the most commonly used topical medication was
      sympathomimetic agents. Additionally, 2.2% of them had used natural herbs
      intranasally, herbs they had collected by themselves and not sold in drugstores.
      The operation most commonly performed was polypectomy. Sufferers from rhinitis
      most commonly consult general practitioners. The percentage of patients using
      alternative medication is limited in comparison with other studies.

PMID- 15853855
TI  - Atherothrombosis: management of patients at risk.
AB  - Vascular disease is the most common cause of mortality and morbidity on a
      worldwide basis and represents a major social burden. Atherothrombosis, which is
      one of the disease processes underlying vascular disease, consists of thrombus
      formation superimposed upon an existing atherosclerotic lesion. A number of
      factors are associated with the risk of developing atherothrombotic clinical
      events, such as myocardial infarction (MI) or ischaemic stroke (IS). The most
      significant of these include a previous vascular event (such as MI or IS),
      hypertension, obesity, diabetes and smoking. Encouraging patients to institute
      lifestyle modifications such as weight loss and smoking cessation can
      significantly reduce the risk of experiencing a primary or secondary vascular
      event. Lifestyle modifications must be supplemented with pharmacological
      therapies if a significant risk reduction is to be achieved. Studies have shown
      that antihypertensives, statins and antithrombotic agents are the most successful
      agents in reducing vascular risk and avoiding unpredictable and life-threatening
      atherothrombotic events.

PMID- 15853856
TI  - The effect of fenofibrate on the levels of high sensitivity C-reactive protein in
      dyslipidaemic hypertensive patients.
AB  - It is now well documented that hypertension is associated with a chronic low
      grade inflammatory state. Levels of high-sensitivity C-reactive protein (hs-CRP),
      a marker of systemic inflammation and a mediator of atherothrombotic disease,
      have been shown to correlate with cardiovascular disease risk. Our objective was
      to evaluate the effect of fenofibrate on the levels of hs-CRP in dyslipidaemic
      hypertensive patients. We selected 30 dyslipidaemic hypertensive patients and 20
      normolipidemic normotensive healthy subjects. Dyslipidaemic hypertensive patients
      were treated with fenofibrate 200 mg/day for 3 months. Serum hs-CRP and metabolic
      parameters were evaluated at baseline in both groups and after fenofibrate
      treatment in dyslipidaemic hypertensive patients. At baseline, significantly
      higher hs-CRP levels were found in dyslipidaemic hypertensive patients than
      normal subjects (0.48 +/- 0.3 vs. 0.15 +/- 0.1 mg/dl, p < 0.01). Total
      cholesterol, low-density lipoprotein cholesterol and triglyceride significantly
      decreased (p < 0.05, p < 0.05 and p < 0.01, respectively), and levels of high
      density lipoprotein cholesterol significantly increased (p < 0.05) after
      treatment with fenofibrate in dyslipidaemic hypertensive group. Levels of hs-CRP
      significantly decreased after fenofibrate treatment from a mean of 0.48 +/- 0.3
      mg/dl to vs. 0.16 +/- 0.2 mg/dl, p < 0.01). Our findings suggest that fenofibrate
      may be used as a first-line therapy for improving the plasma lipids profile as
      well as the chronic low-grade inflammatory state in dyslipidaemia and
      hypertension.

PMID- 15853857
TI  - Use of refractive direct ophthalmoscopy for estimation of refractive error.
AB  - The purpose of this study was to find if direct ophthalmoscopy, a simple
      technique, could be used to give an approximate value of the refractive
      correction for a patient. This would shorten the time and lessen the effort to be
      expended during the following retinoscopic examination done for finding the
      patient's refractive correction. The use of direct ophthalmoscopy for this
      specific purpose is especially desirable where retinoscopic examination is quite
      tedious, e.g. uncooperative patients like children, bed-ridden patients and
      mentally retarded subjects, in patients with a large central corneal opacity and
      in patients having a large refractive error. The study was divided into two
      phases. In phase I, refractive direct ophthalmoscopy followed by classical
      retinoscopy was done for 92 subjects (184 eyes) in the age group of 11-35 years.
      The method of regression analysis was used to find a regression equation relating
      the readings to refractive error determined by the two above techniques. In phase
      II of study, the refractive correction needed for 50 other subjects in the
      similar age group was estimated using this regression equation by inserting their
      respective direct ophthalmoscopy readings. Then, these estimated values and
      classical retinoscopic examination values were compared. The refractive error
      determined after retinoscopy and that derived from regression equation
      (incorporating direct ophthalmoscopy readings) was statistically comparable (t =
      0.52, p = 0.60). The correlation coefficient (r value) between the two methods
      was 0.37. Direct ophthalmoscopic lens reading can be used to give a fairly
      accurate estimate of refractive error in a patient's eye by using a linear
      regression equation, which relates these two examination techniques. The
      magnitude of astigmatic error, however, cannot be obtained.

PMID- 15853858
TI  - Gender-dependent effect of ageing on peripheral insulin action.
AB  - The aim of the present study was to investigate the effect of both gender and age
      on insulin secretion, peripheral insulin effectiveness and insulin-receptor
      binding. Eighty healthy volunteers, 40 females of mean age 38.47 +/- 11.37 years
      and mean BMI 21.99 +/- 2.06 kg/m(2) and 40 males of mean age 34.87 +/- 11.22
      years and mean BMI 22.65 +/- 2.31 kg/m(2), with normal glucose tolerance
      participated in the study. Peripheral insulin effectiveness was measured by the
      artificial endocrine pancreas, using the euglycaemic hyperinsulinaemic clamp
      technique and insulin-receptor binding on circulating mononuclear blood cells.
      Peripheral insulin sensitivity was significantly higher in females as compared to
      males (p < 0.001), while males demonstrated higher total number of insulin
      receptors (p < 0.0001) and number of high-affinity receptors (p < 0.01).
      Peripheral insulin sensitivity decreased with ageing in both males and females,
      the reduction in females being more pronounced (p < 0.05). In the group under 40
      years, the females demonstrated significantly higher insulin sensitivity as
      compared to males (p < 0.001) and lower insulin-receptor binding. Over 40 years,
      females presented higher peripheral insulin sensitivity and higher insulin
      receptor binding. The percentage of specifically bound insulin increased
      significantly with ageing in females and decreased in males. We consider that
      probably the higher androgen level in males affects the post-receptor processes
      in insulin action and despite the higher insulin-receptor binding, males have
      lower insulin sensitivity. The androgen levels in females increase with ageing,
      which could probably affect peripheral insulin sensitivity at the post-receptor
      level. In conclusion, our results demonstrate that when analysing peripheral
      insulin effectiveness and insulin-receptor binding, one should always consider
      both gender and age.

PMID- 15853859
TI  - Beta-cell function and insulin sensitivity contribute to the shape of plasma
      glucose curve during an oral glucose tolerance test in non-diabetic individuals.
AB  - To clarify whether beta-cell function and/or insulin resistance contributes to
      the shape of plasma glucose curve during an oral glucose tolerance test (OGTT),
      we investigated 583 Japanese subjects with normal glucose tolerance (NGT, n =
      306) or impaired glucose tolerance (IGT, n = 277). Each subject was subdivided
      into three shapes of plasma glucose curve as follows: monophasic pattern (M
      type), biphasic pattern (B type) and two peaks (T type). Homeostasis model
      assessment of insulin resistance, quantitative insulin sensitivity check index
      and insulinogenic index were assessed by plasma glucose and insulin
      concentrations obtained at fasting or during an OGTT. There was a greater
      proportion of M type in the IGT group (M = 80.9%, B = 15.5% and T = 3.6%),
      whereas the prevalence of B and T types was much higher in the NGT group (M =
      66.6%, B = 26.5% and T = 6.9%). There were significant differences in the
      proportions of shape types between the NGT and IGT groups (p = 0.0006). Among the
      NGT category, insulin sensitivity was significantly higher in the B type than in
      the M type, and beta-cell function adjusted for insulin resistance was
      significantly higher in the B and T types than in the M type. Among the IGT
      category, no significant differences were seen among the three shape types with
      respect to insulin sensitivity, but the beta-cell function adjusted for insulin
      resistance was significantly lower in the M type than in the B and T types. In
      conclusion, both impaired insulin secretion and insulin resistance may contribute
      to the underlying mechanisms of the shape of plasma glucose curve in Japanese
      subjects.

PMID- 15853860
TI  - Detection and evaluation of salivary antibodies to Helicobacter pylori in
      dyspeptic patients.
AB  - Helicobacter pylori infection is one of the most prevalent infections in humans.
      The high prevalence and the association with peptic ulceration and gastric cancer
      require simple and non-invasive methods for the diagnosis of the infection.
      Detection of salivary anti-H. pylori IgG antibodies has advantages compared with
      those on serum. In this study, salivary immunoglobulin G response to H. pylori
      was evaluated in 100 consecutive dyspeptic patients by enzyme-linked
      immunosorbent assay (ELISA), in comparison with culture and histopathologic
      examination of gastric biopsy specimens obtained at endoscopic procedures and
      assessed the accuracy of salivary diagnosis of the infection. The overall
      sensitivity and specificity of the test were 87 and 73%, respectively. These
      results suggest that saliva testing for H. pylori antibodies could be used
      reliably for screening dyspeptic patients in general practice, especially in
      children in whom venesection is more difficult.

PMID- 15853861
TI  - Maternal carriage and neonatal colonisation of group B streptococcus in eastern
      Turkey: prevalence, risk factors and antimicrobial resistance.
AB  - Our object is to determine the prevalence of group B streptococcus (GBS) carriage
      among pregnant women, the neonatal colonisation rate and the antimicrobial
      susceptibility to formulate a policy for treatment and prevention regarding
      perinatal GBS diseases in eastern Turkey. A total of 150 pregnant women were
      screened for GBS colonisation. Samples were collected from the vagina and the
      rectum of pregnant women, and the ear canal, throat and umbilicus of the neonates
      of colonised mothers. Antimicrobial susceptibility of the isolates was also
      investigated. GBS was isolated in at least one specimen from the 150 women in 48
      cases; it was estimated that, overall, about 32% of the pregnant women and 17.3%
      of overall newborns were colonised with GBS. The overall rate of GBS vertical
      transmission was 54.2% in this study. Maternal colonisation rate was
      significantly higher in younger ages (p < 0.01) when maternal age of 20 years was
      taken as a cut-off point. All isolates were found to be sensitive to penicillin,
      ampicillin, cefazolin and vancomycin. Resistance to erythromycin and clindamycin
      were found to be 13.5 and 2.7%, respectively.

PMID- 15853862
TI  - A national survey of Turkish emergency physicians perspectives regarding family
      witnessed cardiopulmonary resuscitation.
AB  - We investigated Turkish emergency physicians' views regarding family witnessed
      resuscitation (FWR) and to determine the current practice in Turkish academic
      emergency departments with regard to family members during resuscitation. A
      national cross-sectional, anonymous survey of emergency physicians working in
      academic emergency departments was conducted. Nineteen of the 23 university-based
      emergency medicine programs participated in the study. Two hundred and thirty
      nine physicians completed the survey. Of the respondents, 83% did not endorse
      FWR. The most common reasons for not endorsing FWR was reported as higher stress
      levels of the resuscitation team and fear of causing physiological trauma to
      family members. Previous experience, previous knowledge in FWR, higher level of
      training and the acceptance of FWR in the institution where the participant works
      were associated with higher rates of FWR endorsement for this practice among
      emergency physicians.

PMID- 15853863
TI  - The participation of health professionals in a smoking-cessation programme
      positively influences the smoking cessation advice given to patients.
AB  - This study assessed the degree of smoking cessation advice given by health
      professionals, before and after their participation in a smoking cessation study
      using bupropion-sustained release (bupropion SR, Zyban). A total of 690
      physicians and nurses who had smoked an average of 10 cigarettes/day over the
      previous year and were motivated to quit smoking, were randomised in a double
      blind manner to receive bupropion SR (days 1-3, 150 mg/day; days 4-49, 150 mg
      twice daily) or placebo for 7 weeks, with follow-up to week 52. All subjects
      received regular follow-up and brief motivational support throughout the study.
      Questions regarding their smoking cessation advice formed part of the study, with
      the aim of determining whether study participants became more proactive with
      their smoking cessation advice. A positive shift from baseline to end of study
      was observed with respect to the advice and support they gave to their smoking
      patients. These changes were not related to study treatment or current smoking
      status. An increase in advising patients to quit smoking and in offering
      cessation counselling was observed. Participation in a smoking-cessation study by
      physicians and nurses who smoke has a positive effect, regardless of study
      medication, in smoking cessation advice and counselling given to their patients.

PMID- 15853864
TI  - Physiotherapy involvement in non-invasive ventilation hospital services: a
      British Isles survey.
AB  - The aim of this study was to assess the involvement of physiotherapists in the
      delivery of non-invasive ventilation (NIV) services in the British Isles. A
      postal questionnaire was sent to all senior physiotherapists in hospitals
      providing specialist respiratory medicine. The response rate was 88% (269/305).
      Physiotherapists were involved in managing patients using NIV in 212/233
      hospitals that used NIV. The majority of physiotherapists, 97% (206/212), were
      involved in treating patients on NIV. Physiotherapists assessed patients for NIV
      in 68% (145/212) of hospitals and were involved in setting up patients on NIV in
      46% (97/212) of hospitals. There were no major differences between countries,
      within the British Isles, in the level of involvement of Physiotherapists in the
      management of patients on NIV. Physiotherapists need to develop specialist skills
      with regard to assessment and setting up patients on NIV if they want to expand
      their role in the management of patients on NIV.

PMID- 15853865
TI  - Development of a case report review instrument.
AB  - Case reports are valued components of the medical literature. The assessment of
      case reports by editors of medical journals and peer reviewers is largely
      subjective. The purpose of this study was to develop a reliable instrument to
      evaluate the quality of written case reports. Instrument development involved
      review of the literature and the materials provided to peer reviewers who review
      manuscripts, communications with journal editors and discussions of the study
      team. After multiple amendments, the instrument was pilot tested on both
      published and unpublished case reports. Further revisions resulted in the final
      11-item tool. Four independent reviewers evaluated 28 case reports in their
      original submission format that had been submitted to five medical journals. The
      reviewers were blinded to the specific journal that the manuscripts had been
      submitted and to whether the case reports had been accepted for publication.
      Inter-rater reliability was assessed using multirater kappa. Inter-rater
      reliability ranged from 0.03 to 0.90. The four variables with the highest
      agreement between raters were (i) rationale for writing the case report; (ii)
      implications of the case report; (iii) adequacy of the literature review; and
      (iv) overall impression about whether to accept or reject the manuscript (kappas
      of 0.67, 0.67, 0.90 and 0.67, respectively). Six of the instrument's first 10
      variables were highly correlated with the reviewers' decision about whether to
      accept or reject the case report for publication (item 11) (all p < 0.001). No
      correlation existed between the reviewers' decision to accept or reject the
      manuscript and the actual decision that had been made by the various journals.
      The case report review instrument is the first such tool for objectively
      evaluating case reports and appears to have reasonable reliability. Medical
      journals may wish to incorporate the use of this instrument into the decision
      making about a case report's suitability for publication.

PMID- 15853866
TI  - Genes and atherosclerosis: at the origin of the predisposition.
AB  - Atherosclerosis (ATS) is a multifactorial disease caused by the interaction of
      established or emerging risk factors with multiple predisposing genes that
      regulate ATS-related processes. This review will discuss the current knowledge
      concerning the potential role of the genetic variations that could promote and/or
      accelerate ATS, in both animal models and humans. Allelic polymorphisms or
      variations of distinct genes that enhance the risk of ATS frequently occur in the
      general population, but only adequate gene-environment interactions will lead to
      the disease. The main genes so far studied are involved in the regulation of
      processes such as endothelial function, antioxidant potential, coagulation,
      inflammatory response, and lipid, protein and carbohydrate metabolism. The
      detection of candidate genes associated with ATS could allow, in the near future,
      earlier interventions in genetically susceptible individuals. Further, large
      scale population studies are needed to obtain more information on the specific
      gene-environment and drug-gene interactions capable of influencing ATS
      progression.

PMID- 15853867
TI  - Cognitive performance in Alzheimer's disease patients receiving rivastigmine for
      up to 5 years.
AB  - This analysis aimed to assess mini-mental state examination (MMSE) scores in
      patients with Alzheimer's disease who received rivastigmine, an inhibitor of
      acetylcholinesterase and butyrylcholinesterase, for up to 5 years. Rivastigmine
      data came from two pooled open-label extensions of four 6-month, randomised,
      placebo-controlled trials. Projections of decline, had the same patients not been
      treated, were made using a baseline-dependent mathematical model. MMSE data were
      available for 1998 rivastigmine-treated patients and 657, 298 and 83 were still
      on treatment at 3, 4 and 5 years, respectively. The mean (+/-SD) baseline MMSE
      score was 19.3 (+/-4.9). Projected mean scores in model-based untreated patients
      declined below 10 points on the MMSE at about 3 years, while the mean MMSE score
      of patients who remained on rivastigmine stayed above 10 points for 5 years.

PMID- 15853868
TI  - Effectiveness and safety of eprosartan on pulse pressure for the treatment of
      hypertensive patients.
AB  - A multicentre, prospective, non-comparative open-label study was conducted to
      assess the effect of eprosartan, 600 mg/day, on pulse pressure (PP) in patients
      with hypertension (stage I or II, Joint National Committee, sixth report) treated
      in the primary care setting, as well as safety and compliance. The duration of
      treatment was 16 weeks. Eprosartan decreased PP (-13 mmHg), systolic blood
      pressure (SBP) (-26 mmHg), diastolic blood pressure (DBP) (-13 mmHg) and mean
      arterial pressure (MAP) (-17.4 mmHg) significantly (p < 0.0001). The PP/MAP ratio
      changed significantly from 62 to 59%, so that the reduction of PP was 3% higher
      than the overall decrease in MAP. Twenty adverse events, mostly gastrointestinal
      complaints, were recorded in 12 patients (1.9%). Compliance with treatment at the
      end of the study was 94%. Eprosartan was a well-tolerated and an effective drug
      in reducing PP, SBP and DBP below the recommended levels in patients with mild-to
      moderate essential hypertension, allowing a high therapeutic compliance.

PMID- 15853869
TI  - Aripiprazole in schizophrenia: consensus guidelines.
AB  - Schizophrenia is a chronic disabling disease which in the majority of cases
      requires long-term treatment with antipsychotic medication. Before the
      development of atypical antipsychotics, treatment choice was restricted to
      conventional (or typical) antipsychotics, which are known to cause a range of
      side effects including extrapyramidal symptoms. Although atypical agents provide
      a favourable alternative (advocated by the National Institute of Clinical
      Excellence in the UK), they are associated with side effects. These differ
      between agents, but can include weight gain, sedation and hyperprolactinaemia.
      Aripiprazole is a newly available atypical antipsychotic for the treatment of
      schizophrenia. With the apparent imitations of currently available medications,
      aripiprazole provides clinicians with another treatment option. The purpose of
      these guidelines is to outline the consensus reached by the Schizophrenia
      Innovation Working Group on best practice in prescribing and appropriate use of
      aripiprazole in the UK.

PMID- 15853870
TI  - Single-photon emission computed tomography perfusion imaging in the differential
      diagnosis of dementia: a retrospective regional audit.
AB  - A retrospective audit of (99m)Tc-HMPAO SPECT scans was undertaken to assess the
      utility of brain perfusion imaging in a cohort of young cognitively impaired
      patients in whom diagnostic uncertainty remained after standard clinical and
      neuropsychological assessment and structural brain imaging. SPECT scans were
      assessed by five raters (two neurologists and three nuclear medicine specialists)
      on two occasions 6 months apart, first without any clinical data and second with
      brief pertinent clinical information. SPECT diagnoses were compared with
      criterion diagnoses subsequently established by the two neurologists with access
      to all clinical, neuropsychological and neuroimaging data. Despite reasonable
      intra- and interrater reliability, diagnostic accuracy ranged from 32 to 58%.
      SPECT scan normality or abnormality in blind and informed viewings gave
      respective sensitivities of 77 and 71%, specificities of 44 and 38%, positive
      predictive values of 88 and 87% and negative predictive values of 27 and 18%.
      Calculating pairwise disease group comparisons, likelihood ratios suggested some
      diagnostic gain in differentiating AD from 'not AD' and from FTD/focal syndromes.
      SPECT scanning was of little help in establishing diagnoses in this cohort of
      patients, a finding which supports the conclusion of the American Academy of
      Neurology evidence-based review that SPECT imaging cannot be recommended for
      either the initial or the differential diagnosis of suspected dementia because it
      has not demonstrated superiority to clinical criteria.

PMID- 15853871
TI  - Simultaneous midline laser glossectomy with palatopharyngeal surgery for
      obstructive sleep apnoea syndrome.
AB  - We investigate the outcome of performing tongue base reduction surgery and
      palatopharyngeal surgery in a single stage to determine whether the same-stage
      midline laser glossectomy (MLG) with extended uvulopalatal flap (EUPF) for
      obstructive sleep apnoea syndrome (OSAS) is a safe and effective procedure. Six
      male patients with a history of severe OSAS were recruited into the retrospective
      study. They were the first patients to undergo the MLG with EUPF procedure.
      Patients were identified to have retropalatal and hypopharyngeal sites of
      obstruction on the basis of fiberoptic endoscopy with Muller's manoeuvre and
      three-dimensional computerised tomography. No significant adverse events
      occurred. The follow-up polysomnography (6-month follow-up) revealed that the
      mean respiratory disturbance index from 50.7 to 11.6, snoring index from 230.9 to
      137.3 and the minimal oxygen saturation from 76.3 to 88.8. This study confirms
      that the same-stage MLG with EUPF for OSAS is a safe and effective procedure.

PMID- 15853872
TI  - Munchausen syndrome revisited.

PMID- 15853873
TI  - Talking about death -'I can ... '.

PMID- 15853875
TI  - Bacillus subtilis antibiotics: structures, syntheses and specific functions.
AB  - The endospore-forming rhizobacterium Bacillus subtilis- the model system for Gram
      positive organisms, is able to produce more than two dozen antibiotics with an
      amazing variety of structures. The produced anti-microbial active compounds
      include predominantly peptides that are either ribosomally synthesized and post
      translationally modified (lantibiotics and lantibiotic-like peptides) or non
      ribosomally generated, as well as a couple of non-peptidic compounds such as
      polyketides, an aminosugar, and a phospholipid. Here I summarize the structures
      of all known B. subtilis antibiotics, their biochemistry and genetic analysis of
      their biosyntheses. An updated summary of well-studied antibiotic regulation
      pathways is given. Furthermore, current findings are resumed that show roles for
      distinct B. subtilis antibiotics beyond the "pure" anti-microbial action: Non
      ribosomally produced lipopeptides are involved in biofilm and swarming
      development, lantibiotics function as pheromones in quorum-sensing, and a
      "killing factor" effectuates programmed cell death in sister cells. A discussion
      of how these antibiotics may contribute to the survival of B. subtilis in its
      natural environment is given.

PMID- 15853876
TI  - The role of nucleoid-associated proteins in the organization and compaction of
      bacterial chromatin.
AB  - The bacterial chromosomal DNA is folded into a compact structure called nucleoid.
      The shape and size of this 'body' is determined by a number of factors. Major
      players are DNA supercoiling, macromolecular crowding and architectural proteins,
      associated with the nucleoid, which are the topic of this MicroReview. Although
      many of these proteins were identified more than 25 years ago, the molecular
      mechanisms involved in the organization and compaction of DNA have only started
      to become clear in recent years. Many of these new insights can be attributed to
      the use of recently developed biophysical techniques.

PMID- 15853877
TI  - The McbR repressor modulated by the effector substance S-adenosylhomocysteine
      controls directly the transcription of a regulon involved in sulphur metabolism
      of Corynebacterium glutamicum ATCC 13032.
AB  - In a recent proteomics study we have shown that the mcbR gene of Corynebacterium
      glutamicum ATCC 13032 most probably encodes a transcriptional repressor of the
      TetR type, which regulates the expression of at least six genes involved in the
      synthesis of sulphur-containing amino acids. By means of DNA microarray
      hybridizations we detected 86 genes with enhanced transcription in an mcbR mutant
      when compared with the wild-type strain. Bioinformatic analysis identified the
      inverted repeat 5'-TAGAC-N6-GTCTA-3' as a consensus sequence within the upstream
      region of 22 genes and operons, suggesting that the transcription of at least 45
      genes is directly controlled by the McbR repressor. These 45 genes encode a
      variety of functions in (S-adenosyl)methionine and cysteine biosynthesis, in
      sulphate reduction, in uptake and utilization of sulphur-containing compounds and
      in transcriptional regulation. The function of the inverted repeat motif as
      potential McbR binding site in front of the genes hom, cysI, cysK, metK and mcbR
      was verified experimentally by competitive electrophoretic mobility shift
      analysis. A systematic search for the potential effector substance modulating the
      function of McbR revealed that only S-adenosylhomocysteine prevented the binding
      of McbR to its target sequence. These results indicate that the transcriptional
      repressor McbR directly regulates a set of genes comprising all aspects of
      transport and metabolism of the macroelement sulphur in C. glutamicum. As the
      activity of McbR is modulated by S-adenosylhomocysteine, a major product of
      transmethylation reactions, the results point also to a novel regulatory
      mechanism in bacteria to control the biosynthesis of S-adenosylmethionine.

PMID- 15853878
TI  - An unusual primary sigma factor in the Bacteroidetes phylum.
AB  - The presence of housekeeping gene promoters with a unique consensus sequence in
      Bacteroides fragilis, previously described by Bayley et al. (2000, FEMS Microbiol
      Lett 193: 149-154), suggested the existence of a particular primary sigma factor.
      The single rpoD-like gene observed in the B. fragilis genome, and similarly in
      those of other members of the Bacteroidetes phylum, was found to be essential. It
      encodes a protein, sigma(ABfr), of only 32.7 kDa that is produced with equal
      abundance during all phases of growth and was concluded to be the primary sigma
      factor. sigma(ABfr) and its orthologues in the Bacteroidetes are unusual primary
      sigma factors in that they lack region 1.1, have a unique signature made up of 29
      strictly identical amino acids and are the only RpoD factors that cluster with
      the RpoS factors. Although binding to the Escherichia coli core RNA polymerase,
      sigma(ABfr) does not support transcription initiation from any promoter when it
      is part of the heterologous holoenzyme, while in the reconstituted homologous
      holoenzyme it does so only from typical B. fragilis, including rrs, promoters but
      not from the lacUV5 or RNA I promoters.

PMID- 15853879
TI  - A conserved set of pilin-like molecules controls type IV pilus dynamics and
      organelle-associated functions in Neisseria gonorrhoeae.
AB  - Type IV pili (Tfp) play central roles in prokaryotic cell biology and disease
      pathogenesis. As dynamic filamentous polymers, they undergo rounds of extension
      and retraction modelled as pilin subunit polymerization and depolymerization
      events. Currently, the molecular mechanisms and components influencing Tfp
      dynamics remain poorly understood. Using Neisseria gonorrhoeae as a model system,
      we show that mutants lacking any one of a set of five proteins sharing structural
      similarity to the pilus subunit are dramatically reduced in Tfp expression and
      that these defects are suppressed in the absence of the PilT pilus retraction
      protein. Thus, these molecules are not canonical assembly factors but rather act
      as effectors of pilus homeostasis by promoting extension/polymerization events in
      the presence of PilT. Furthermore, localization studies support the conclusion
      that these molecules form a Tfp-associated complex and influence levels of PilC,
      the epithelial cell adhesin, in Tfp-enriched shear fractions. This is the first
      time that the step at which individual pilin-like proteins impact on Tfp
      expression has been defined. The findings have important implications for
      understanding Tfp dynamics and fundamental Tfp structure/function relationships.

PMID- 15853880
TI  - A yeast genetic system for the identification and characterization of substrate
      proteins transferred into host cells by the Legionella pneumophila Dot/Icm
      system.
AB  - The Dot/Icm system is a type IVb secretion system used by Legionella pneumophila
      to modulate vesicular transport in both protozoan and mammalian host cells. It
      has been shown that proteins and processes that are highly conserved in all
      eukaryotic cells are targets for some of the proteins injected by the Dot/Icm
      system. For example, the Legionella protein RalF was shown previously to be a
      Dot/Icm substrate that functions as a guanine nucleotide exchange factor (GEF)
      for the Arf family of eukaryotic small GTP-binding proteins. Here we show that
      ectopic production of the RalF protein in Saccharomyces cerevisiae interferes
      with yeast growth. Inhibition of yeast growth was found to be dependent on the
      ability of RalF to function as an Arf-GEF in vivo. The possibility that other
      Dot/Icm substrate proteins would have the capacity to interfere with yeast growth
      was used as a rationale to screen plasmid libraries containing random fragments
      of Legionella chromosomal DNA positioned downstream of a galactose-inducible
      promoter. This screen identified Legionella proteins that conferred a conditional
      growth defect when overproduced by yeast cultured in the presence of galactose.
      Most of the Legionella proteins identified were determined to be substrates of
      the Dot/Icm system. This screen led to the identification of a new Dot/Icm
      substrate protein that was called YlfA, for yeast lethal factor A. A paralogue of
      YlfA was identified on an unlinked region of the Legionella chromosome and this
      protein was also translocated by the Dot/Icm system. It was determined that a
      hydrophobic region near the N-terminus of the YlfA protein and an adjacent region
      predicted to form a coiled-coil domain were necessary for a biological activity
      that interfered with yeast growth. The YlfA protein did not decorate the
      Legionella-containing vacuole during the first 7 h of infection but could be
      observed on the endoplasmic reticulum (ER)-derived replicative vacuole and on
      punctate structures throughout the host cell at later stages. Ectopic production
      of YlfA in mammalian cells revealed that the N-terminal hydrophobic domain in
      YlfA was able to localize the protein to early secretory organelles, including
      endoplasmic reticulum. These studies show that yeast genetics can be exploited to
      identify and characterize proteins that are injected into host cells by bacterial
      pathogens that utilize type IV secretion systems for pathogenesis.

PMID- 15853881
TI  - Silkworm pathogenic bacteria infection model for identification of novel
      virulence genes.
AB  - Silkworms are killed by injection of pathogenic bacteria, such as Staphylococcus
      aureus and Streptococcus pyogenes, into the haemolymph. Gene disruption mutants
      of S. aureus whose open reading frames were previously uncharacterized and that
      are conserved among bacteria were examined for their virulence in silkworms. Of
      these 100 genes, three genes named cvfA, cvfB, and cvfC were required for full
      virulence of S. aureus in silkworms. Haemolysin production was decreased in these
      mutants. The cvfA and cvfC mutants also had attenuated virulence in mice. S.
      pyogenes cvfA-disrupted mutants produced less exotoxin and had attenuated
      virulence in both silkworms and mice. These results indicate that the silkworm
      infection model is useful for identifying bacterial virulence genes.

PMID- 15853882
TI  - The PilC adhesin of the Neisseria type IV pilus-binding specificities and new
      insights into the nature of the host cell receptor.
AB  - Type IV pili of Neisseria gonorrhoeae and Neisseria meningitidis mediate the
      first contact to human mucosal epithelial cells, an interaction which is also
      critical for the interaction with vascular endothelial cells. The PilC proteins
      have been characterized as the principal pilus-associated adhesin. Here we show
      that PilC2 exhibits a defined cell and tissue tropism, as it binds to human
      epithelial and endothelial cell lines, but not to human T cells or fibroblasts.
      Piliated gonococci and PilC2 exhibit similar patterns of binding to human
      epithelial and endothelial cells, supporting the function of PilC as the key
      pilus adhesin. Although CD46 has previously been suggested to be a pilus
      receptor, several observations indicate that neisserial type IV pili and the
      pilus adhesin PilC2 interact with epithelial cells in a CD46 independent manner.
      Biochemical approaches were used to characterize the nature of host cell factors
      mediating binding of piliated gonococci and PilC2 protein. Our data indicate that
      the putative host cell receptor for gonococcal pili and the PilC2 pilus adhesin
      is a surface protein. Glycostructures were found to not be involved in binding.
      Moreover, we observed the uptake of purified PilC2 protein together with its
      receptor via receptor-mediated endocytosis and subsequent receptor re-exposure on
      the cell surface. Our data support the existence of a specific pilus receptor and
      provide intriguing information on the nature of the receptor.

PMID- 15853883
TI  - Iron limitation induces SpoT-dependent accumulation of ppGpp in Escherichia coli.
AB  - In Escherichia coli the beta-lactam mecillinam specifically inhibits penicillin
      binding protein 2 (PBP2), a peptidoglycan transpeptidase essential for
      maintaining rod shape. We have previously shown that PBP2 inactivation results in
      a cell division block and that an increased concentration of the nucleotide
      ppGpp, effector of the RelA-dependent stringent response, confers mecillinam
      resistance and allows cells to divide as spheres in the absence of PBP2 activity.
      In this study we have characterized an insertion mutation which confers
      mecillinam resistance in wild-type and DeltarelA strains but not in
      DeltarelADeltaspoT strains, devoid of ppGpp. The mutant has an insertion in the
      fes gene, coding for enterochelin esterase. This cytoplasmic enzyme hydrolyses
      enterochelin-Fe(3+) complexes, making the scavenged iron available to the cells.
      We show that inactivation of the fes gene causes iron limitation on rich medium
      plates and a parallel SpoT-dependent increase of the ppGpp pool, as judged by the
      induction of the iron-regulated fiu::lacZ fusion and the repression of the
      stringently controlled P1(rrnB)::lacZ fusion respectively. We further show, by
      direct ppGpp assays, that iron starvation in liquid medium produces a SpoT
      dependent increase of the ppGpp pool, strongly suggesting a role for iron in the
      balance of the two activities of SpoT, synthesis and hydrolysis of (p)ppGpp.
      Finally, we present evidence that ppGpp exerts direct or indirect positive
      control on iron uptake, suggesting a simple homeostatic regulatory circuit: iron
      limitation leads to an increased ppGpp pool, which increases the expression of
      iron uptake genes, thereby alleviating the limitation.

PMID- 15853884
TI  - Biosynthesis of the red antibiotic, prodigiosin, in Serratia: identification of a
      novel 2-methyl-3-n-amyl-pyrrole (MAP) assembly pathway, definition of the
      terminal condensing enzyme, and implications for undecylprodigiosin biosynthesis
      in Streptomyces.
AB  - The biosynthetic pathway of the red-pigmented antibiotic, prodigiosin, produced
      by Serratia sp. is known to involve separate pathways for the production of the
      monopyrrole, 2-methyl-3-n-amyl-pyrrole (MAP) and the bipyrrole, 4-methoxy-2,2'
      bipyrrole-5-carbaldehyde (MBC) which are then coupled in the final condensation
      step. We have previously reported the cloning, sequencing and heterologous
      expression of the pig cluster responsible for prodigiosin biosynthesis in two
      Serratia sp. In this article we report the creation of in-frame deletions or
      insertions in every biosynthetic gene in the cluster from Serratia sp. ATCC
      39006. The biosynthetic intermediates accumulating in each mutant have been
      analysed by LC-MS, cross-feeding and genetic complementation studies. Based on
      these results we assign specific roles in the biosynthesis of MBC to the
      following Pig proteins: PigI, PigG, PigA, PigJ, PigH, PigM, PigF and PigN. We
      report a novel pathway for the biosynthesis of MAP, involving PigD, PigE and
      PigB. We also report a new chemical synthesis of MAP and one of its precursors, 3
      acetyloctanal. Finally, we identify the condensing enzyme as PigC. We reassess
      the existing literature and discuss the significance of the results for the
      biosynthesis of undecylprodigiosin by the Red cluster in Streptomyces coelicolor
      A3(2).

PMID- 15853885
TI  - A role for the Plasmodium falciparum RESA protein in resistance against heat
      shock demonstrated using gene disruption.
AB  - During erythrocyte invasion, the Plasmodium falciparum Ring-infected erythrocyte
      surface antigen (RESA) establishes specific interactions with spectrin. Based on
      analysis of strains with a large chromosome 1 deletion, RESA has been assigned
      several functions, none of which is firmly established. Analysis of parasites
      with a disrupted resa1 gene and isogenic parental or resa3-disrupted controls
      confirmed the critical role of RESA in the surface reactivity of immune adult
      sera on glutaraldehyde-fixed ring stages. Absence of RESA did not influence
      merozoite invasion or erythrocyte membrane rigidity, was associated with a modest
      increase of cytoadhesion to CD36 under conditions of flow, but resulted in marked
      susceptibility to heat shock. resa1-KO-infected erythrocytes were prone to heat
      induced vesiculation like uninfected erythrocytes, whereas parental or resa3-KO
      infected erythrocytes remained undamaged. Furthermore, a 6 h exposure of ring
      stages at 41 degrees C resulted in 33% culture inhibition of resa1-KO parasites
      while marginally impacting parental and resa3-KO parasite growth. This points to
      a role for RESA in protecting the infected erythrocyte cytoskeleton during
      febrile episodes. Infection patterns of resa1-KO and parental parasites in
      Saimiri sciureus indicated that RESA does not, at least on its own, modulate
      virulence in the squirrel monkey, as had been previously suggested.

PMID- 15853886
TI  - Compensatory role of PspA, a member of the phage shock protein operon, in rpoE
      mutant Salmonella enterica serovar Typhimurium.
AB  - Sigma(E) is an alternative sigma factor that responds to and ameliorates
      extracytoplasmic stress. In Salmonella enterica serovar Typhimurium (S.
      Typhimurium), sigma(E) is required for oxidative stress resistance, stationary
      phase survival and virulence in mice. Microarray analysis of stationary-phase
      gene expression in rpoE mutant bacteria revealed a dramatic increase in
      expression of pspA, a member of the phage shock protein (psp) operon. The psp
      operon can be induced by filamentous bacteriophages or by perturbations of
      protein secretion, and is believed to facilitate the maintenance of proton motive
      force (PMF). We hypothesized that increased pspA expression may represent a
      compensatory response to the loss of sigma(E) function. Increased pspA expression
      was confirmed in rpoE mutant Salmonella and also observed in a mutant lacking the
      F(1)F(0) ATPase. Alternatively, expression of pspA could be induced by exposure
      to CCCP, a protonophore that disrupts PMF. An rpoE pspA double mutant strain was
      found to have a stationary-phase survival defect more pronounced than that of
      isogenic strains harbouring single mutations. The double mutant strains were also
      more susceptible to killing by CCCP or by a bactericidal/permeability-increasing
      protein (BPI)-derived anti-microbial peptide. Using fluorescence ratio imaging,
      differences were observed in the Deltapsi of wild-type and rpoE or pspA mutant
      bacteria. These findings suggest that pspA expression in S. Typhimurium is
      induced by alterations in PMF and a functional sigma(E) regulon is essential for
      the maintenance of PMF.

PMID- 15853887
TI  - Evidence of selection for low cognate amino acid bias in amino acid biosynthetic
      enzymes.
AB  - If the enzymes responsible for biosynthesis of a given amino acid are repressed
      and the cognate amino acid pool suddenly depleted, then derepression of these
      enzymes and replenishment of the pool would be problematic, if the enzymes were
      largely composed of the cognate amino acid. In the proverbial "Catch 22", cells
      would lack the necessary enzymes to make the amino acid, and they would lack the
      necessary amino acid to make the needed enzymes. Based on this scenario, we
      hypothesize that evolution would lead to the selection of amino acid biosynthetic
      enzymes that have a relatively low content of their cognate amino acid. We call
      this the "cognate bias hypothesis". Here we test several implications of this
      hypothesis directly using data from the proteome of Escherichia coli. Several
      lines of evidence show that low cognate bias is evident in 15 of the 20 amino
      acid biosynthetic pathways. Comparison with closely related Salmonella
      typhimurium shows similar results. Comparison with more distantly related
      Bacillus subtilis shows general similarities as well as significant differences
      in the detailed profiles of cognate bias. Thus, selection for low cognate bias
      plays a significant role in shaping the amino acid composition for a large class
      of cellular proteins.

PMID- 15853888
TI  - In vitro analysis of sequence requirements for the excision reaction of the
      Bacteroides conjugative transposon, CTnDOT.
AB  - CTnDOT, a Bacteroides conjugative transposon (CTn), initiates its transfer by
      excising to form a circular intermediate. This process has been shown to be
      complex, involving an unusual DNA intermediate with a short region of heterology
      and several CTn-encoded proteins. No information was available, however, about
      the sizes or sequence requirements of the att sites (attL and attR) at the ends
      of the integrated element where the processing occurs during excision. Using a
      newly developed in vitro competition excision assay, we have now localized attL
      to 153 bp and attR to 179 bp. Excision of CTnDOT involves staggered cuts that
      produce 5 bp chromosomal sequences at either end of the CTn. These 5 bp sequences
      (coupling sequences) form a region of heterology in the excised circular
      intermediate. Site-directed mutations that made the coupling sequences
      complementary and removed the region of heterology had no effect on excision.
      Thus, heterology is not essential. Mutagenesis of sequences adjacent to the
      coupling sequences revealed a 6 bp site in attR that was essential for excision.
      Mutating the analogous region in attL had little effect on excision. Regions
      within the attL site that appear to play a role in excision were found by
      introducing small insertions (phasing mutations) that could interfere with
      protein-protein or protein-DNA interactions. Similar insertion mutations in attR
      had no significant effect on excision. These results support the hypothesis that
      the CTnDOT excision reaction is asymmetrical with respect to likely protein
      binding sites and involves multiple protein-DNA interactions.

PMID- 15853889
TI  - Measuring chromosome dynamics on different time scales using resolvases with
      varying half-lives.
AB  - The bacterial chromosome is organized into multiple independent domains, each
      capable of constraining the plectonemic negative supercoil energy introduced by
      DNA gyrase. Different experimental approaches have estimated the number of
      domains to be between 40 and 150. The site-specific resolution systems of closely
      related transposons Tn3 and gammadelta are valuable tools for measuring supercoil
      diffusion and analysing bacterial chromosome dynamics in vivo. Once made, the
      wild-type resolvase persists in cells for time periods greater than the cell
      doubling time. To examine chromosome dynamics over shorter time frames that are
      more closely tuned to processes like inducible transcription, we constructed a
      set of resolvases with cellular half-lives ranging from less than 5 min to 30
      min. Analysing chromosomes on different time scales shows domain structure to be
      dynamic. Rather than the 150 domains detected with the Tn3 resolvase, wild-type
      cells measured over a 10 min time span have more than 400 domains per genome
      equivalent, and some gyrase mutants exceed 1000.

PMID- 15853890
TI  - Activation of both acfA and acfD transcription by Vibrio cholerae ToxT requires
      binding to two centrally located DNA sites in an inverted repeat conformation.
AB  - The Gram-negative bacterium Vibrio cholerae is the infectious agent responsible
      for the disease Asiatic cholera. The genes required for V. cholerae virulence,
      such as those encoding the cholera toxin (CT) and toxin-coregulated pilus (TCP),
      are controlled by a cascade of transcriptional activators. Ultimately, the direct
      transcriptional activator of the majority of V. cholerae virulence genes is the
      AraC/XylS family member ToxT protein, the expression of which is activated by the
      ToxR and TcpP proteins. Previous studies have identified the DNA sites to which
      ToxT binds upstream of the ctx operon, encoding CT, and the tcpA operon,
      encoding, among other products, the major subunit of the TCP. These known ToxT
      binding sites are seemingly dissimilar in sequence other than being A/T rich.
      Further results suggested that ctx and tcpA each has a pair of ToxT binding sites
      arranged in a direct repeat orientation upstream of the core promoter elements.
      In this work, using both transcriptional lacZ fusions and in vitro copper
      phenanthroline footprinting experiments, we have identified the ToxT binding
      sites between the divergently transcribed acfA and acfD genes, which encode
      components of the accessory colonization factor required for efficient intestinal
      colonization by V. cholerae. Our results indicate that ToxT binds to a pair of
      DNA sites between acfA and acfD in an inverted repeat orientation. Moreover, a
      mutational analysis of the ToxT binding sites indicates that both binding sites
      are required by ToxT for transcriptional activation of both acfA and acfD. Using
      copper-phenanthroline footprinting to assess the occupancy of ToxT on DNA having
      mutations in one of these binding sites, we found that protection by ToxT of the
      unaltered binding site was not affected, whereas protection by ToxT of the mutant
      binding site was significantly reduced in the region of the mutations. The
      results of further footprinting experiments using DNA templates having +5 bp and
      +10 bp insertions between the two ToxT binding sites indicate that both binding
      sites are occupied by ToxT regardless of their positions relative to each other.
      Based on these results, we propose that ToxT binds independently to two DNA sites
      between acfA and acfD to activate transcription of both genes.

PMID- 15853891
TI  - Clustering requires modified methyl-accepting sites in low-abundance but not high
      abundance chemoreceptors of Escherichia coli.
AB  - Chemotaxis signalling complexes of Escherichia coli, composed of chemoreceptors,
      CheA and CheW, form clusters located predominantly at cell poles. As the only
      kind of receptor in a cell, high-abundance receptors are polar and clustered
      whereas low-abundance chemoreceptors are polar but largely unclustered. We found
      that clustering was a function of the cytoplasmic, carboxyl-terminal domain and
      that effective clustering was conferred on low-abundance receptors by addition of
      the approximately 20-residue sequence from the carboxyl terminus of either high
      abundance receptor. These sequences are different but share a carboxyl-terminal
      pentapeptide that enhances adaptational covalent modification and allows a
      physiological balance between modified and unmodified methyl-accepting sites,
      implying that receptor modification might influence clustering. Thus we
      investigated directly effects of modification state on chemoreceptor clustering.
      As the sole receptor type in a cell, low-abundance receptors were clustered only
      if modified, but high-abundance receptors were clustered independent of extent of
      modification. This difference could mean that the two receptor types are
      fundamentally different or that they are poised at different positions in the
      same conformational equilibrium. Notably, no receptor perturbation we tested
      altered a predominant location at cell poles, emphasizing a distinction between
      determinants of clustering and polar localization.

PMID- 15853892
TI  - DksA represses ribosomal gene transcription in Pseudomonas aeruginosa by
      interacting with RNA polymerase on ribosomal promoters.
AB  - In Escherichia coli transcription of ribosomal RNA (rRNA) is regulated by the H
      NS and Fis proteins, as well as by the small signal molecule ppGpp and the
      initiating nucleotides. During amino acid starvation, the concentration of ppGpp
      increases, and binding of this alarmone to RNA polymerase (RNAP) leads to
      inhibition of rRNA transcription, a regulatory event called stringent response.
      Here we show that in Pseudomonas aeruginosa DksA, a protein with pleiotropic
      effects, is a negative regulator of rRNA transcription both during exponential
      growth and stringent conditions. A dksA mutant overexpresses rRNA, without being
      affected in the production of ppGpp. Cell-fractionation and chromosome
      immunoprecipitation experiments demonstrate that DksA is associated with DNA, in
      particular with promoters of ribosomal genes in vivo. The binding to rRNA
      promoters specifically increases during stringent response, and correlates with
      the binding of RNAP to these regions. Moreover DksA can be copurified with RNAP
      subunits in vivo. DNA band shift experiments show that DksA, in synergy with
      ppGpp, increases the binding of RNAP to ribosomal promoters. Therefore DksA might
      be a new regulator of rRNA transcription in P. aeruginosa.

PMID- 15853893
TI  - Characterization of TetD as a transcriptional activator of a subset of genes of
      the Escherichia coli SoxS/MarA/Rob regulon.
AB  - In Escherichia coli, SoxS, MarA and Rob form a closely related subset of the
      AraC/XylS family of positive regulators, sharing approximately 42% amino acid
      sequence identity over the length of SoxS and the ability to activate
      transcription of a common set of target genes that provide resistance to redox
      cycling compounds and antibiotics. On the basis of its approximately 43% amino
      acid sequence identity with SoxS, MarA and Rob, TetD, encoded by transposon Tn10,
      appears to be a fourth member of the subset. However, although its expression has
      been shown to be negatively regulated by TetC and not inducible by tetracycline,
      the physiological function of TetD is unknown. Accordingly, in the work presented
      here, we initiate a molecular characterization of TetD. We show that expression
      of TetD activates transcription of a subset of the SoxS/MarA/Rob regulon genes
      and confers resistance to redox-cycling compounds and antibiotics. We show that
      mutations in the putative TetD binding site of a TetD-activatable promoter and a
      mutation in the protein's N-terminal DNA recognition helix interfere with
      transcription activation, thereby indicating that TetD directly activates target
      gene transcription. Finally, we show that TetD, like SoxS and MarA, is
      intrinsically unstable; however, unlike SoxS and MarA, TetD is not degraded by
      Lon or any of the cell's known cytoplasmic ATP-dependent proteases. Thus, we
      conclude that TetD is a bona fide member of the SoxS/MarA/Rob subfamily of
      positive regulators.

PMID- 15853894
TI  - Unraveling innate immunity using large scale N-ethyl-N-nitrosourea mutagenesis.
AB  - With the mouse genome almost entirely sequenced and readily accessible to all who
      wish to examine it, the challenge across most biological disciplines now lies in
      the decipherment of gene and protein function rather than in the realm of gene
      identification per se. In the field of innate immunity, forward genetic methods
      have repeatedly been applied to identify key sensors, adapters, and effector
      molecules. However, most spontaneous mutations that affect innate immune function
      have been mapped and cloned, and the need for new monogenic phenotypes has been
      felt evermore keenly. N-Ethyl-N-nitrosourea (ENU) mutagenesis is an efficient
      tool for the creation of aberrant monogenic innate immune response phenotypes. In
      this review, we will discuss the potential of the forward genetic approach and
      ENU mutagenesis to identify new genes and new functions of known genes related to
      innate immunity.

PMID- 15853895
TI  - Genomic characterization of KIR2DL4 in families and unrelated individuals reveals
      extensive diversity in exon and intron sequences including a common frameshift
      variation occurring in several alleles.
AB  - The KIR2DL4 gene including a portion of exon 1 through exon 9 was sequenced from
      two families and eight cell lines from the International Histocompatibility
      Workshop (IHWS). Two known alleles and eight variants were detected. Overall,
      there were five synonymous and three non-synonymous changes when the variants
      were compared to the coding sequences of the most closely related known alleles
      plus a common frameshift change in five of the variant alleles. Alignment of the
      new variants with all known alleles showed that the regions encoding the
      extracellular region and the cytoplasmic tail were the most polymorphic. Two non
      synonymous changes, P146H and L161V, occurred in an extracellular immunoglobulin
      like domain. Five of the eight variants had a single adenine deletion in the exon
      encoding the transmembrane region, potentially resulting in a truncated protein
      lacking the cytoplasmic tail. The distribution of the deletion variant among many
      KIR2DL4 alleles may explain the high frequency of this variation in the
      population. Four of the eight consanguineous IHWS cell lines were found to be
      heterozygous for KIR2DL4 carrying two alleles that differed from one another by a
      few nucleotide substitutions. Analysis of intron sequences in the families
      revealed the nature and distribution of interspersed repeat elements which
      comprise 46% of the KIR2DL4 nucleotide sequence and consist of 12 elements
      including six SINEs (13.73% of the total length), one LINE (12.41%), and five LTR
      elements (19.51%). The results revealed the presence of extensive diversity in
      the KIR2DL4 gene. This is the first extensive report providing both exon and
      intron data in related individuals.

PMID- 15853896
TI  - Selective monomorphic and polymorphic HLA class I antigenic determinant loss in
      surgically removed melanoma lesions.
AB  - The analysis of human leukocyte antigen (HLA) class I allospecificity expression
      in malignant lesions has been hampered by the limited availability of HLA class I
      allospecificity-specific monoclonal antibodies (mAbs) which stain tissues in
      immunohistochemical (IHC) reactions. During the 12th International
      Histocompatibility Workshop, the HLA and cancer component made available a panel
      of mAbs capable of detecting monomorphic, locus- and allo-specific HLA class I
      antigenic determinants in surgically removed frozen tissue sections by IHC
      staining. In the present study, we have utilized this panel of mAbs to analyze
      the expression of HLA class I allospecificities in 33 primary and in 11
      metastatic lesions surgically removed from HLA-typed patients with malignant
      melanoma, as this information contributes to determine the extent of HLA class I
      antigen abnormalities in melanoma lesions. HLA class I antigens were
      downregulated in six (18.2%) of the primary lesions and in six (54.5%) of the
      metastatic lesions. Selective loss of HLA-A and HLA-B antigens was detected in
      two (6.1%) and in one (3.0%), respectively, of the primary lesions, but in none
      of the metastases. HLA-A and HLA-B antigens were downregulated in three (9.1%)
      and four (36.4%) of the primary and metastatic lesions, respectively. Selective
      loss of one or more HLA class I allospecificities was found in 10 (33.0%) and two
      (18.0%) of the 33 primary and 11 metastatic melanoma lesions analyzed,
      respectively. HLA class I antigen abnormalities were present in 16 (48.5%) of the
      33 primary lesions analyzed (i.e. six lesions demonstrating abnormal reactivity
      with HLA class I monomorphic-specific mAb, two lesions demonstrating selective
      abnormal reactivity with HLA-B locus-specific mAb, one lesion demonstrating
      selective abnormal reactivity with HLA-A and HLA-B locus-specific mAbs, and seven
      lesions demonstrating selective abnormal reactivity with HLA class I allele
      specific mAb). Furthermore, HLA class I antigen abnormalities were present in
      nine (81.8%) of the 11 metastatic lesions analyzed (i.e. six lesions
      demonstrating abnormal reactivity with HLA class I monomorphic-specific mAb, one
      lesion demonstrating selective abnormal reactivity with HLA-A locus-specific mAb,
      and two lesions demonstrating selective abnormal reactivity with HLA class I
      allele-specific mAb). It cannot be ruled out that the frequency of HLA class I
      allospecificity abnormalities is higher, as the expression of several HLA class I
      allospecificities could not be investigated because of the lack of appropriate
      probes. The frequency of HLA class I antigen defects in primary lesions was
      significantly correlated with primary lesion thickness, an important prognostic
      marker in melanoma, arguing for a potential clinical significance of HLA class I
      antigen abnormalities in melanoma. In conclusion, the results of the present
      study (i) demonstrate that the frequency of HLA class I allospecificity
      abnormalities in primary melanoma lesions is markedly higher than that of total
      HLA class I antigen downregulation described in the literature; (ii) corroborate
      our previous findings that staining of melanoma lesions with mAb to monomorphic
      determinants of HLA class I antigens does not detect selective HLA class I
      allospecificity loss; and (iii) demonstrate for the first time selective loss of
      antigenic determinants expressed on HLA class I molecules in melanoma lesions.
      The latter finding indicates that at least two mAbs recognizing distinct
      antigenic determinants on the HLA molecule being investigated should be used for
      IHC staining of tissue sections in order to prove that lack of immunostaining
      reflects actual loss of the corresponding HLA molecule and not selective loss of
      antigenic determinants.

PMID- 15853897
TI  - Analysis of 250 HLA-B44 genotypes in European Caucasoids: high diversity and
      preferential ABCDRB1 associations in B*4402, B*4403, and B*4405 haplotypes.
AB  - Based on high-resolution DNA typing within 235 pedigrees, a total of 250 HLA
      A/B/C/DRB1/DRB3 genotypes have been characterized. These comprise 129 different
      B44 haplotypes, of which 73.6% occurred only once. Only four different B*44
      alleles were identified: B*4402-4405, with B*4402 and B*4403 haplotypes
      accounting for 57.6 and 36.8%, respectively, of all haplotypes. Although the
      relative numbers of different A/B/C/DRB1/B3 haplotypic associations were similar
      in both B*4402 and B*4403 haplotypes, the genotypic profiles were quite different
      in the two groups. When associated with the A*0101, A*0201, A*2402, A*3201, and
      A*6801 alleles, a much more extensive polymorphism of B*4402 haplotypes with
      respect to HLA-C and DRB1 associations was disclosed. On the other hand, B*4403
      haplotypes were more diverse in the A23-B44 and A29-B44 groups with respect to
      DRB1 associations. Considering B-C linkage, B*4402-Cw*0501, B*4402-Cw*0704,
      B*4402-Cw*1604, B*4403-Cw*0401, B*4403-Cw*1601, B*4404-Cw*1601, and B*4405
      Cw*0202 accounted for 98% of all genotypes. Eight A/B/C/DRB1 haplotypes occurred
      at a relative genotypic frequency of >0.015, with A*2902-B*4403-Cw*1601-DRB1*0701
      (11.2%) and A*0201-B*4402-Cw*0501-DRB1*0401 (8.4%) as the two most frequent
      genotypes. Some A and DRB1 alleles were predominantly, if not exclusively,
      associated with specific B-C pairs: A*0301 with B*4402-Cw*0501 and B*4403
      Cw*0401; A*2301 with B*4403-Cw*0401; A*2608 with B*4402-Cw*0501; A*2902 with
      B*4403-Cw*1601; DRB1*0101/0401/0403/0404/1101/1104/0801/1301/1302 with B*4402
      Cw*0501; and DRB1*0701 with B*4403-Cw*1601. On the basis of this dataset and our
      experience with searches for phenotypically matched unrelated stem cell donors,
      several ABDR haplotypes were identified that would confer a higher probability of
      B44- and C-incompatibility. The analysis of 112 consecutive unrelated stem cell
      donor searches revealed that 24% of the 400 tested donors were B44-mismatched,
      and that no single B44 allele- matched donor could be identified for only 7% of
      the patients. HLA-C incompatibility rate was 22.2% for the patients with > or =1
      B44 allele-matched donor(s). This dataset can therefore be used as a predictive
      tool for B44- and C-disparities in unrelated stem cell transplantation.

PMID- 15853898
TI  - Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the
      Korean population.
AB  - High-resolution human leukocyte antigen (HLA) typing exposes the unique patterns
      of HLA allele and haplotype frequencies in each population. In this study, HLA-A,
      -B, -C, -DRB1, and -DQB1 genotypes were analyzed in 485 apparently unrelated
      healthy Korean individuals. A total of 20 HLA-A, 43 HLA-B, 21 HLA-C, 31 HLA-DRB1,
      and 14 HLA-DQB1 alleles were identified. Eleven alleles (A*0201, A*1101, A*2402,
      A*3303, B*1501, Cw*0102, Cw*0302, Cw*0303, DQB1*0301, DQB1*0302, and DQB1*0303)
      were found in more than 10% of the population. In each serologic group, a maximum
      of three alleles were found with several exceptions (A2, B62, DR4, DR14, and
      DQ6). In each serologic group exhibiting multiple alleles, two major alleles were
      present at 62-96% (i.e. A*0201 and A*0206 comprise 85% of A2-positive alleles).
      Multiple-locus haplotypes estimated by the maximum likelihood method revealed 51
      A-C, 43 C-B, 52 B-DRB1, 34 DRB1-DQB1, 48 A-C-B, 42 C-B-DRB1, 46 B-DRB1-DQB1, and
      30 A-C-B-DRB1-DQB1 haplotypes with frequencies of more than 0.5%. In spite of
      their high polymorphism in B and DRB1, identification of relatively small numbers
      of two-locus (B-C and DRB1-DQB1) haplotypes suggested strong associations of
      those two loci, respectively. Five-locus haplotypes defined by high-resolution
      DNA typing correlated well with previously identified serology-based haplotypes
      in the population. The five most frequent haplotypes were: A*3303-Cw*1403-B*4403
      DRB1*1302-DQB1*0604 (4.2%), A*3303-Cw*0701/6-B*4403-DRB1*0701-DQB1*0201/2 (3.0%),
      A*3303-Cw*0302-B*5801-DRB1*1302-DQB1*0609 (3.0%), A*2402-Cw*0702-B*0702-DRB1*0101
      DQB1*0501 (2.9%), and A*3001-Cw*0602-B*1302-DRB1*0701-DQB1*0201/2 (2.7%). Several
      sets of allele level haplotypes that could not be discriminated by routine HLA-A,
      -B, and -DRB1 low-resolution typing originated from allelic diversity of A2, B61,
      DR4, and DR8 serologic groups. Information obtained in this study will be useful
      for medical and forensic applications as well as in anthropology.

PMID- 15853899
TI  - High-resolution genotyping of HLA-DQA1 in the GoKinD study and identification of
      novel alleles HLA-DQA1*040102, HLA-DQA1*0402 and HLA-DQA1*0404.
AB  - In order to achieve high-resolution HLA-DQA1 genotyping, it is necessary to
      identify polymorphisms in exons 1, 2 and 3. We present a high-resolution sequence
      based typing (SBT) strategy for genotyping exons 1, 2 and 3 of the polymorphic
      HLA-DQA1 locus. This method is an improvement upon previously presented methods,
      because it utilizes the minimum number of SSP-PCR assays to obtain clear DNA
      sequence in both the forward and reverse directions of all three exons. All known
      HLA-DQA1 alleles are resolved with the exception of HLA-DQA1*010101 and HLA
      DQA1*010102 for which the distinguishing polymorphism is located in exon 4 and
      does not result in an amino acid change. This method has enabled our laboratory
      to identify three new HLA-DQA1 alleles - HLA-DQA1*040102, HLA- DQA1*0402 and HLA
      DQA1*0404 - in the Genetics of Kidneys in Diabetes (GoKinD) study population.
      Additionally, we present single-allele amplification methods, which identify the
      coding sequences of HLA-DQA1 exons 1, 2, 3, intron 2 and 300 bp of the HLA-DQA1
      promoter (QAP). This study, also describes the QAP for most of the known HLA-DQA1
      alleles, three HLA-DQA2 promoter sequences and the intron 2 sequences for HLA
      DQA1*040101, HLA-DQA1*040102, HLA-DQA1*0402 and HLA-DQA1*0404.

PMID- 15853900
TI  - HLA class II DPB1, DQA1, DQB1, and DRB1 genotypic associations with occupational
      allergic cough to Bunashimeji mushroom.
AB  - We previously reported that two-third of workers in a Bunashimeji mushroom
      (Hypsizigus marmoreus) farm complained of respiratory allergic symptoms, but one
      third workers did not suffer from such symptoms even when working for a long
      period. CD4+ T-helper (Th) cells increased, and Th2/Th1 ratio increased in the
      allergic workers. To address these immunological backgrounds, we have
      investigated whether there is any relationship between mushroom allergy and human
      leukocyte antigen (HLA) class II alleles of DPB1, DQA1, DQB1, and DRB1 by using
      the polymerase chain reaction-restriction fragment length polymorphism (RFLP) and
      sequencing-based typing methods. We observed that the allele frequencies of
      DQA1*0103, DQB1*0601, and DRB1*0803 were significantly higher in the workers
      having no allergic symptoms than allergic workers (DQA1*0103: 57 vs 25%,
      DQB1*0601: 49 vs 14%, and DRB1*0803: 29 vs 0%). However, this phenomenon was not
      seen in workers producing another kind of mushroom, Honshimeji (Lyophyllum
      aggregatum). The HLA-DRB1*0803 allele alone, the DRB1*0803, DQA1*0103, DQB1*0601
      haplotype, or both were negatively associated with allergy to Bunashimeji, and
      these alleles might be involved in the prevention of Bunashimeji mushroom
      specific respiratory allergy.

PMID- 15853901
TI  - Oligonucleotide microarray for HLA-DRB1 genotyping: preparation and clinical
      evaluation.
AB  - In this study, HLA-DRB1 gene was genotyped by using the microarray technique.
      Oligonucleotide probes were designed based on partial sequences of various
      genotypes of HLA-DRB1, and were fixed on a silylated slide to form a microarray.
      The second exon of HLA-DRB1 gene in the extracted genomic DNA samples was
      amplified and labelled by means of polymerase chain reaction (PCR); then it was
      hybridized to the microarray. The microarray was scanned, and the result was
      analysed in order to determine the genotypes of HLA-DRB1 of the tested sample. A
      total of 1574 of 1592 clinical samples had accordant results of genotypes in
      either microarray assay or PCR-SSP assay; 8 of 10 samples that had inconsistent
      results of genotypes were proved to be microarray-assay reliable by confirmation
      of DNA sequencing. It is concluded that microarray is an alternative reliable
      method for HLA-DRB1 genotyping.

PMID- 15853902
TI  - Genetic study of ICAM1 in clinical malaria in Senegal.
AB  - Many genes have been implicated in the risk of severe malaria, generally based on
      candidate gene studies in case/control populations. Among these genes, there has
      been conflicting reports for the implication of a variant of the intercellular
      adhesion molecule 1 (ICAM1), ICAM1(Kilifi), in the risk of severe malaria, while
      in vitro studies provided independent support for a functional role of this
      variant. In order to explore the possible implication of ICAM1 in the
      susceptibility/resistance to malaria and to try to understand its clinical
      relevance in the disease process, we have conducted linkage and association
      studies of ICAM1 in two Senegalese villages located in regions of endemic
      malaria. We explored the full genetic variability of ICAM1, and tested it on
      several clinical malarial traits which are under genetic control, focusing
      principally on variables related to the parasite density and the number of
      malarial attacks. Our study provides no evidence for a role of ICAM1 variability
      on the malarial phenotypes studied.

PMID- 15853903
TI  - HLA antigens in Greek children with allergic bronchial asthma.
AB  - The aim of our study was to investigate the genetic linkage between mite allergic
      bronchial asthma and HLA class I and II antigens and haplotypes. Sixty Greek
      children with allergic bronchial asthma due to mite sensitivity (Dermatophagoides
      pteronyssinus and Dermatophagoides farinae) and their family members were typed
      for HLA class I and II antigens (total 263 subjects). One hundred and twenty-five
      healthy, unrelated Greek children without medical history of atopy were also
      typed as control group. Major histocompatibility complex class I and II gene
      analysis revealed that only HLA-DRB1*04 and HLA-DQA1*0301 alleles are possibly
      important factors in the development of atopic asthma in Greek children with
      sensitivity to mites. No significant differences among the HLA-DRB1*04 subtypes
      have been established. Transmission disequilibrium test revealed that no specific
      HLA-A, -B, -DRB1, -DQA1 and -DQB1 alleles were transmitted preferentially to the
      affected children. HLA-DQB1*0301-4 alleles were associated with high levels of
      total serum immunoglobulin E in affected children. The study of the HLA
      haplotypes failed to demonstrate any significant association between any extended
      or natural selection haplotype and mite allergic bronchial asthma in Greek
      children.

PMID- 15853904
TI  - A new HLA-A allele, HLA-A*6824, identified in three unrelated individuals.
AB  - A novel allele, human leukocyte antigen (HLA)-A*6824, has been identified in
      three unrelated individuals of northwestern European origin in a period of less
      than 4 months, implying that this allele may be quite common in this population.
      HLA-A*6824 differs from A*680102 by a single nucleotide change at position 275 in
      exon 2, which results in a conservative amino acid substitution from lysine to
      arginine in the peptide-binding groove at codon 68.

PMID- 15853905
TI  - Routine HLA-B genotyping with PCR-sequence-specific oligonucleotides detects a
      B*52 variant (B*5206).
AB  - A new human leukocyte antigen (HLA)-B allele was found during routine typing of
      samples for a German unrelated bone marrow donor registry, the "Aktion
      Knochenmarkspende Bayern". After first interpretation of data of two independent
      low-resolution sequence-specific oligonucleotide typing tests, a B*51 variant was
      suggested. Further analysis via sequence-based typing identified the sequence as
      new B*52 allele. This new allele officially assigned as B*5206 differs from HLA
      B*520102 by one nucleotide exchange in exon 2. The mutation is located at
      nucleotide position 274, at which a cytosine is substituted by a thymine leading
      to an amino acid change at protein position 67 from serine (TCC) to phenylalanine
      (TTC).

PMID- 15853906
TI  - Identification of three novel HLA class I alleles: HLA-A*0261, HLA-B*1585 and HLA
      B*1587.
AB  - Three novel human leucocyte antigen (HLA) class I alleles have been characterized
      by means of direct DNA sequencing analysis. HLA-A* 0261 showed sequence variation
      at conserved codon. It differs from HLA-A* 020601 by a single-nucleotide
      substitution at codon 57 (CCG-->GCG) resulting in an amino acid change from Pro
      to Ala. The sequences of HLA-B*1585 are similar to those of HLA-B*15010101, but
      differed five nucleotides on exon 3 resulting in three amino acid changes at
      residues 94 (Thr-->Ile), 95 (Leu-->Ile) and 103 (Val-->Leu). Likewise, HLA-B*1587
      is identical to HLA-B*15010101 except at codons 80-83 (Asn-Leu-Arg-Gly-->Ile-Ala
      Leu-Arg) which has been replaced by HLA-Bw4 motif. These alleles seemed to be
      generated by either a point mutation or a gene conversion-like event from alleles
      existing in the population with high frequencies.

PMID- 15853907
TI  - Bone marrow donor routine HLA typing identified a novel B*07 allele, B*0734,
      confirmed by allele-specific DNA cycle sequencing.
AB  - In this article, we report the identification of a new human leukocyte antigen-B
      allele in a sample that was tested in our routine typing for bone marrow donors.
      This novel allele officially designed B*0734 was found in a female donor of
      Bavarian Caucasoid origin (Laboratory code 121036). The search for unrelated bone
      marrow donors was initiated by the Aktion Knochenmarkspende Bayern. In comparison
      to the common B*070201, B*0734 differs at four nucleotide positions, 412 (G-->A),
      539 (G-->T), 559 (G-->A) and 560 (A-->C) causing three amino acid substitutions,
      at postion 138 Asp-->Asn, at position 180 Arg-->Leu and at position 187 Glu-
      >Thr.

PMID- 15853908
TI  - A novel HLA-B*55 allele, HLA-B*5514, found in a DNA sample derived from a bone
      marrow donor.
AB  - In this study, we report the identification of a new human leucocyte antigen-B
      (HLA-B) allele in a sample that was found in our routine typing. This novel
      allele, officially designed HLA-B*5514, was found in a male donor of Bavarian
      Caucasoid origin (Laboratory code: 117562) typed in order for a request of the
      bone marrow donor registry Aktion Knochenmarkspende Bayern. Although this novel
      allele was added to the HLA-B*55 family by the Nomenclature Committee, the next
      related alleles were found in the HLA-B*56 group; HLA-B*5612 differing in six
      positions from HLA-B*5514 is the closest related allele.

PMID- 15853909
TI  - Identification of a novel HLA-DQB1 allele, DQB1*0314, by sequence-based typing in
      the Korean population.
AB  - The polymorphism of HLA class II genes is largely confined to the exon 2 region.
      Sequence analysis of exon 2 of the DQB1 gene revealed the novel polymorphism in
      the Korean population. The new DQB1 allele, DQB1*0314, was differed from
      DQB1*0304 only at codon 46 (GAG-->GGG), corresponding to non-synonymous amino
      acid change (Glu-->Gly).

PMID- 15853910
TI  - Peptide-binding characteristics of the novel allele DRB1*0112 are probably
      identical to DRB1*0101.
AB  - So far 11 different amino acid variants of the HLA-DRB1*01 family have been
      reported. We here describe the identification of a new HLA-DRB1*01 allele in a
      healthy female Caucasian. The allele was detected by sequencing-based typing
      during high-resolution typing of a potential unrelated donor from the North
      German Bone Marrow Registry (NKR). Compared with DRB1*010101, to which it is
      closest, the new variant is characterized by a new replacement mutation (G-->T)
      at nucleotide position 202 of exon 2, resulting in the amino acid substitution
      Arg-->Leu at position 72. Because this amino acid position is not involved in
      peptide binding or T-cell interaction, it is likely to represent a permissive
      mismatch to the more common HLA-DRB1*0101 allele.

PMID- 15853911
TI  - Candida albicans cell-wall fraction exacerbates collagen-induced arthritis in
      mice.
AB  - The immune system generates a specific response against most pathogens, while
      developing tolerance to self-antigens. Commensal micro-organisms can express
      molecular structures that mimic self-epitopes. During acute infection, such
      pathogen may activate self-reactive T-cell clones promoting autoimmunity. In the
      present study, a beta-mercaptoethanol cell-wall fraction (MF) from Candida
      albicans was injected into the paw of naive ICR and BALB/c mice and into the paw
      of ICR mice with bovine collagen type II-induced arthritis (CIA). Development of
      inflammation was monitored for 6 weeks. MF provoked a stable swelling and
      histopathologic changes in the injected joint, with a predominance of T-helper 1
      cytokines in ICR mice. In BALB/c strain, a swelling was observed only in the
      early period, with no evidence of joint pathology. Injection of the MF fraction
      exacerbated the disease in ICR mice with CIA, and this was associated with the
      elevation of interferon-gamma and anti-bovine type II collagen (bCII)
      immunoglobulin G2a antibodies. These results indicate that component(s) in the MF
      fraction cross-react with bCII-specific cells.

PMID- 15853912
TI  - In vivo transduction of thymic dendritic cells with adenovirus and its potential
      use in acute inflammatory diseases.
AB  - Dendritic cells (DC) represent a potential target for gene therapy. In their
      ability to process antigens and present them to T cells, DC have been allocated a
      unique role as initiators of the immune response in both the innate and acquired
      immunity. Recent in vitro studies have showed the feasibility of DC transduction
      with adenoviral recombinants. In cancer therapy, targeting of DC with adenovirus
      has been proved to be effective in inhibiting tumour growth, as well as in
      reducing the number of tumour metastases. The aim of our study is to evaluate the
      feasibility of in vivo transduction of DC in a murine lymphocyte-rich compartment
      (thymus) as a potential treatment for acute inflammatory diseases. Nearly 50% of
      the total thymic DC were transduced with a first-generation adenoviral construct
      following intrathymic injection, and post-transductional inflammation was
      neglectable. Transduction of thymic cells with adenoviral recombinants was able
      to induce the expression of an intracellular protein (beta-galactosidase, green
      fluorescent protein), as well as the secretion of human interleukin-10, within
      the local compartment. Furthermore, this induction of the latter significantly
      decreased thymic apoptosis in the applied model of acute bacterial peritonitis
      (cecal ligation and puncture).

PMID- 15853913
TI  - Sodium alginate as a novel therapeutic option in experimental colitis.
AB  - The potential therapeutic effect of low-viscosity sodium alginate (LVA) was
      studied in a rat model of acute colitis induced by intracolonic administration of
      acetic acid. This experimental model produced a significant ulcerative colitis.
      Induction of colitis also significantly enhanced the serum and colonic mucosal
      cytokine (IL-6 and TNF-alpha) and eicosanoid (LTB4 and PGE2) levels, which
      paralleled with the severity of colitis. LVA solution was administered orally as
      drinking water at concentration of 0.5% (W/V) for 1 week. The tolerability and
      inhibitory effect of LVA on matrix metalloproteinase-2 (MMP-2) were tested using
      WEHI-164 cell line and zymography method. The results showed that LVA therapy is
      able to significantly reduce colonic damage score, histological lesion, serum and
      colonic mucosal IL-6, TNF-alpha, LTB4 and PGE2 levels in treated group compared
      with nontreated controls. Moreover, in vitro examinations revealed that treatment
      with LVA could diminish MMP-2 activity. It is concluded that LVA is able to
      suppress acetic acid-induced colitis in rats. Some of the action of LVA may be
      associated with its inhibitory effects on cytokine and eicosanoid production and
      MMP-2 activity. Our data suggest that LVA could potentially be a novel
      therapeutic option for inflammatory bowel disease.

PMID- 15853914
TI  - Complement dependency of splenic localization of pneumococcal polysaccharide and
      conjugate vaccines.
AB  - The immune response to polysaccharides is initiated when polysaccharides bind
      complement factor C3d, and these polysaccharide-C3d complexes subsequently
      localize on splenic marginal zone B cells strongly expressing CD21 (complement
      receptor 2). Infants and children under the age of 2 years have low or absent
      expression of CD21 on their marginal zone B cells, and consequently do not
      adequately respond to polysaccharides. In contrast, polysaccharide-protein
      conjugate vaccines are able to induce antibodies at this young age. Conjugate
      vaccines apparently overcome the necessity for CD21-C3d interaction for an
      antipolysaccharide immune response. We demonstrate in a rat model that
      localization of pneumococcal polysaccharides on splenic marginal zone B cells
      indeed is complement dependent. We also show that pneumococcal conjugates do not
      specifically localize on splenic marginal zone B cells and that splenic
      localization of polysaccharide conjugates is independent of the presence of
      complement. Thus, the induction of antipolysaccharide antibodies by conjugate
      vaccines apparently can occur independently of CD21-C3d interaction. These basic
      findings may explain the effectiveness of conjugated vaccines in young children
      and may open the way for their application in other patient groups.

PMID- 15853915
TI  - Immunology of cutaneous vasculitis associated with both etanercept and
      infliximab.
AB  - Targeted inhibition of tumour necrosis factor-alpha (TNF-alpha) is an effective
      therapy in rheumatoid arthritis and Crohn's disease (CD). Infliximab, a
      monoclonal murine-human chimeric antibody to TNF-alpha, and etanercept, a fusion
      protein of two p75 chains of the TNF receptor II and the Fc portion of IgG1, are
      generally well tolerated. Rarely does clinically significant autoimmunity,
      including drug-induced lupus and vasculitis occur. Immunologic mechanisms
      underlying the development of autoimmunity in the presence of such powerful
      immunosuppressants are unknown. We describe a patient with CD, who developed
      cutaneous vasculitis on etanercept, which worsened significantly with switch to
      infliximab. Investigation of the associated systemic and local immune response
      demonstrated the absence of human antichimera antibodies, but mRNA for T-helper 1
      cytokines, chemokines and defensins in the skin and elevated angiogenesis factors
      in the serum, as determined by reverse-transcriptase polymerase chain reaction
      and enzyme-linked immunosorbent assay. Histopathology revealed a lymphocytic
      vasculitis composed of T cells. A permanent B-cell line (MD-B) producing
      extremely high amounts of chemokines and interleukin-6 was established from this
      patient's peripheral blood. Lesions progressed despite discontinuation of the
      drugs and (40 mg/day) prednisone but almost completely resolved with single dose
      of (0.1 mg/kg) intravenous dexamethasone, which may be therapy of choice for this
      reaction. A few lesions (<10) have recurred intermittently over 4 years of follow
      up, suggesting possible persistence of this TNF-inhibitor-triggered autoimmune
      disease.

PMID- 15853916
TI  - Effect of LACK and KMP11 on IFN-gamma production by peripheral blood mononuclear
      cells from cutaneous and mucosal leishmaniasis patients.
AB  - The immune modulatory properties of recombinant antigens Kinetoplasmid membrane
      protein-11 (KMP11) and Leishmania homologue of receptors for activated C kinase
      (LACK) in cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML) patients
      were evaluated. The mean levels of interferon-gamma (IFN-gamma) in soluble
      leishmania antigen (SLA) stimulated peripheral blood mononuclear cells (PBMC) of
      ML and CL patients were 5625 +/- 2333 pg/ml and 4422 +/- 3665 pg/ml,
      respectively. IFN-gamma was not detected in cultures stimulated with KMP11 or
      LACK. Interleukin-10 (IL-10) concentration in SLA, KMP11 and LACK-stimulated PBMC
      of ML patients was 13 +/- 12 pg/ml, 285 +/- 388 pg/ml and 802 +/- 483 pg/ml,
      respectively. Addition of KMP11 or LACK to SLA-stimulated PBMC of CL and ML
      patients enhanced IL-10 production (P < 0.05). Addition of KMP11 decreased IFN
      gamma levels by 52% in CL patients and by 19% in ML patients. Addition of LACK to
      SLA-stimulated cultures decreased IFN-gamma levels by 58% in CL patients and by
      30% in ML patients. Neutralization of IL-10 abrogated the downregulatory effect
      of LACK and KMP11. The modulatory properties of LACK and KMP11 are due to
      induction of IL-10 production and may be helpful for attenuating chronic
      inflammatory diseases. However, in some clinical conditions, as demonstrated for
      ML, these molecules are not able to suppress the IFN-gamma response, even
      inducing IL-10 production.

PMID- 15853917
TI  - Antibodies against extractable nuclear antigen in non-Hodgkin lymphoma patients.
AB  - Autoantibodies are found at higher frequency in malignant lymphoproliferative
      diseases and also the association of these diseases with autoimmunity is
      documented. However precise mechanisms are not yet understood beyond these
      findings. We measured anti-extractable nuclear antigen (ENA) antibodies in non
      Hodgkin's lymphoma patients before, during and after chemotherapy and compared
      these values to healthy controls. Sixty six lymphoma patients' data were compared
      with 30 healthy patients' data. ENA levels were significantly elevated in
      untreated lymphoma patients compared with healthy controls (1.85 U/l versus 0.68
      U/l, P < 0.05). This increase could be observed during and after treatment as
      well. Those patients who responded well to initial chemotherapy were demonstrated
      with gradually increasing ENA antibody titers compared with the rest of patients,
      where a gradual decrease in titer was found. These findings are not yet
      statistically significant, but may help us further understand immunological
      reactions beyond the treatment of malignant lymphomas.

PMID- 15853918
TI  - Reduced release of intact and cleaved urokinase receptor in stimulated whole
      blood cultures from human immunodeficiency virus-1-infected patients.
AB  - The blood levels of the soluble forms of the urokinase receptor (suPAR) are
      increased in human immunodeficiency virus (HIV)-1-infected patients. This study
      investigated whether the release of urokinase-type plasminogen activator receptor
      (uPAR) in whole-blood cultures was affected by HIV infection. The release of
      different uPAR forms in whole-blood cultures incubated 24 h with or without
      phytohemagglutinin and lipopolysaccharide was analysed in 47 HIV patients and 19
      controls. suPAR was measured by enzyme-linked immunosorbent assay (ELISA) (bulk
      suPAR) and three different time-resolved fluorescence immunoassays measuring
      three-domain suPAR [suPAR(I-III)], three- and two-domain suPAR [suPAR(I-III) +
      suPAR(II-III)] and one-domain suPAR [suPAR(I)]. The uPAR release was correlated
      to leucocyte subpopulations and plasma levels of suPAR. The stimulated net whole
      blood culture release of bulk-uPAR, uPAR(I-III), uPAR(II-III) and uPAR(I) was
      reduced in HIV patients (all P < 0.01), whereas the spontaneous bulk-uPAR and
      uPAR(I-III) release was increased in HIV patients (both P < 0.05). The stimulated
      uPAR release in whole-blood cultures correlated well to leucocytes and
      circulating suPAR levels in controls, whereas the correlation was weaker to
      leucocytes and nonexisting to circulating suPAR levels in HIV patients. These
      findings demonstrate that HIV infection affects stimulated and spontaneous uPAR
      release in whole-blood cultures. Given that high blood levels of suPAR in HIV
      patients are linked to immune activation, the perturbations in uPAR release in
      whole-blood cultures from HIV patients may also reflect immune activation.

PMID- 15853919
TI  - The autoreactivity of therapeutic intravenous immunoglobulin (IVIG) preparations
      depends on the fractionation methods used.
AB  - Natural immunoglobulin G (IgG) autoantibodies are present in the plasma of
      healthy individuals and, as a result, in pooled therapeutic intravenous
      immunoglobulin (IVIg) preparations. The production processes of commercial IVIg
      preparations involve different fractionation and virus-inactivation steps that
      include in some cases treatments at extreme conditions. Different physical and
      chemical treatments are known to augment greatly the reactivity of natural
      autoantibodies to self-antigens. It is not clear to what extent the self
      reactivity of IVIg preparations is due to the presence of natural IgG antibodies
      in the plasma pools used for fractionation, and to what extent it is due to the
      treatments that the IgG molecules have been subjected to during the fractionation
      process. We compared the binding of seven different commercial IVIg preparations
      to human liver antigens. All studied IVIg's could be clearly separated into two
      distinct groups: those that possess significant self-reactivity and those with
      low binding to self-antigens. Increased self-binding was seen in the preparations
      produced using a fractionation step at low pH. The treatment of IVIg at low pH
      resulted in increasing the inhibitory effect of the pooled IgG on PHA-induced
      proliferation of human peripheral blood mononuclear cells. IVIg's with high and
      low self-binding may have different immunomodulating activities when infused to
      autoimmune patients.

PMID- 15853920
TI  - Allogeneic dendritomas induce anti-tumour immunity against metastatic colon
      cancer.
AB  - Colon cancer (CC) is one of the most common malignancies in the Western world.
      Although surgical resection is the first choice worldwide, at this point an
      effective approach for the treatment of patients with metastasis and cancer
      recurrence post-operation has not yet been found. The aim of this study was to
      investigate the role of the allogeneic dendritomas from fusion of dendritic cells
      (DC) and metastatic CC cells in the activation of anti-tumour immunity against
      metastatic CC. Dendritomas were generated by fused allogeneic human peripheral
      blood DC with metastatic CC cells using 50% polyethylene glycol. The
      proliferation of the T cells and the toxicity of the cytotoxic T lymphocytes were
      observed after T cell pulsed with allogeneic dendritomas. The activated ratios of
      CD4+T helper 1 and CD8+Tc1 cells were about 51.55 and 65.60% after T cells were
      mixed with fusions for 24 h, which higher than those of controls. The
      proliferation of T cells were significantly higher than those of control after T
      cell pulsed with dendritomas (P < 0.01). Significantly, the activated CD8+ T
      lymphocytes effectively lysed the CC cells. These results demonstrate that
      allogeneic dendritomas activate T-cell responses against metastatic CC cells.

PMID- 15853921
TI  - Cytokine mRNA expression and iron status in children living in a malaria endemic
      area.
AB  - Iron deficiency has been reported to affect both malaria pathogenesis and cell
      mediated immune responses; however, it is unclear whether the protection afforded
      by iron deficiency is mediated through direct effects on the parasite, through
      immune effector functions or through both. We have determined cytokine mRNA
      expression levels in 59 children living in a malaria endemic area on the coast of
      Kenya who we selected on the basis of their biochemical iron status. Real-time
      quantitative reverse transcriptase polymerase chain reaction analysis of cytokine
      mRNA levels of peripheral blood mononuclear cells (PBMC) obtained from these
      children showed an association between interleukin-4 (IL-4) mRNA levels and all
      the biochemical indices of iron that we measured. Furthermore, IL-10 mRNA was
      higher in parasite blood smear-positive children than in blood smear-negative
      children irrespective of their iron status. This study suggests that IL-4
      expression by PBMC may be affected by iron status.

PMID- 15853922
TI  - A sero-epidemiological survey of gelatin sensitization in young Japanese children
      during the 1979-1996 period.
AB  - Recently, an increasing number of adverse reactions in children inoculated with
      live attenuated virus vaccines containing gelatin have been reported. However,
      the distribution, magnitude and rate of gelatin sensitization in the Japanese
      population have not been established. Here, the purpose was to investigate the
      distribution of children with positive gelatin immunoglobulin G (IgG) and/or IgE
      in Japan and to ascertain whether the incidence of positive antigelatin antibody
      cases among the general population, as reflected in the sample employed here, has
      been increasing during the period in question. The presence of IgE and IgG
      antibodies were measured against gelatin in 1600 panel sera collected from
      different age groups of Japanese children in Hokkaido/Sapporo from 1979 through
      1996. Among the subjects, 39 had gelatin IgG- and/or IgE-positive sera, and these
      were correlated with the time of obtaining the sera as well as with the age of
      the subjects. The older the subject and the later the period, the higher the sero
      incidence. Japanese children have become increasingly sensitized to gelatin,
      especially since the mid-1990s.

PMID- 15853923
TI  - Distinct interethnic differences in immunoglobulin G class/subclass and
      immunoglobulin M antibody responses to malaria antigens but not in immunoglobulin
      G responses to nonmalarial antigens in sympatric tribes living in West Africa.
AB  - The well-established relative resistance to malaria observed in the Fulani as
      compared with other sympatric tribes in West Africa has been attributed to their
      higher levels of serum immunoglobulin (Ig) G antibodies to malarial antigens. In
      this study, we confirm and extend the previous findings by analyses of the levels
      of IgM, IgG and IgG subclasses of anti-malarial antibodies in asymptomatic
      individuals of different sympatric tribes in Burkina Faso (Fulani/Mossi) and Mali
      (Fulani/Dogon). The Fulani showed significantly higher median concentrations of
      anti-malarial IgG and IgM antibodies than the sympatric tribes at both locations.
      Although the overall subclass pattern of antibodies did not differ between the
      tribes, with IgG1 and IgG3 as dominant, the Fulani showed consistently
      significantly higher levels of these subclasses as compared with those of the non
      Fulani individuals. No significant differences were seen in the levels of total
      IgG between the tribes, but the Fulani showed significantly higher levels of
      total IgM than their neighbours in both countries. While the antibody levels to
      some nonmalarial antigens showed the same pattern of differences seen for
      antibody levels to malaria antigens, no significant such differences were seen
      with antibodies to other nonmalarial antigens. In conclusion, our results show
      that the Fulani in two different countries show higher levels of anti-malarial
      antibodies than sympatric tribes, and this appears not to be a reflection of a
      general hyper-reactivity in the Fulani.

PMID- 15853924
TI  - Association of interferon-gamma +874(T/A) single nucleotide polymorphism with the
      rate of tryptophan catabolism in healthy individuals.
AB  - Abstract Mechanisms induced by tryptophan (trp) catabolism are important in the
      regulation of both normal and pathogenetic immune responses. The key enzyme is
      indoleamine-pyrrole 2,3-dioxygenase (EC 1.13.11.42) (IDO) which converts trp to
      kynurenine (kyn), the main toxic metabolite. It is known that interferon-gamma
      (IFN-gamma) is able to activate IDO. We wanted to analyse whether the strength of
      this mechanism would be under genetic control. To this end, we analysed the IFN
      gamma+874(T/A) genotypes, which are known to have an effect on IFN-gamma
      production, of 309 healthy blood donors and correlated these to the levels of trp
      and kyn in their blood. The data obtained demonstrate that the presence of the
      high producer T allele was associated with increased IDO activity (i.e. elevated
      kyn and kyn/trp levels), but this effect was observed only in females. These data
      show that trp catabolism is genetically controlled by the IFN-gamma gene and may
      thus be operative in those disease conditions associated with the polymorphisms
      of the IFN-gamma gene.

PMID- 15853925
TI  - New mathematical methods in pharmacokinetic modeling.
AB  - In recent years, several new methods for the mathematical modeling have gradually
      emerged in pharmacokinetics, and the development of pharmacokinetic models based
      on these methods has become one of the most rapidly growing and exciting
      application-oriented sub-disciplines of the mathematical modeling. The goals of
      our MiniReview are twofold: i) to briefly outline fundamental ideas of some new
      modeling methods that have not been widely utilized in pharmacokinetics as yet,
      i.e. the methods based on the following concepts: linear time-invariant dynamic
      system, artificial-neural-network, fuzzy-logic, and fractal; ii) to arouse the
      interest of pharmacological, toxicological, and pharmaceutical scientists in the
      given methods, by sketching some application examples which indicate the good
      performance and perspective of these methods in solving pharmacokinetic problems.

PMID- 15853926
TI  - Structural analysis of the genes for human arylamine N-acetyltransferases and
      characterisation of alternative transcripts.
AB  - Arylamine N-acetyltransferases are polymorphic drug-metabolising enzymes. The
      human isoforms, NAT1 and NAT2, are encoded by two genes with intronless coding
      regions. Human NAT1 protein is found in many tissues, unlike NAT2 which is
      present predominantly in the intestine and liver. We describe the exon-intron
      structure of the human NAT genes by analysing data from genomic databases.
      Comparison of expressed sequence tags, matching NAT gene sequences, with the
      sequence of human chromosome 8 implied the presence of 8 non-coding exons located
      51.5, 51.4, 12.3, 11.9, 10.8, 9.6, 5.2 and 2.6 kb upstream of the single coding
      exon of the NAT1 gene. A number of expressed sequence tags also indicated
      transcription initiation from the upstream region adjacent to the NAT1 coding
      exon, consistent with earlier studies. The NAT2 gene consists of one previously
      described non-coding and one coding exon, located 8.6 kb apart. These findings
      were also confirmed by RT-PCR, using cDNA from heart, brain, placenta, lung,
      liver, skeletal muscle, kidney and pancreas. Alternatively spliced NAT1
      transcripts were found in all tissues. Transcription of the NAT2 gene was also
      detected in these tissues and was demonstrated to start either from the non
      coding exon or from immediately upstream of the coding exon. Comparison of the RT
      PCR products provided an initial estimate of the relative amounts of the
      different NAT transcripts expressed in each tissue. Finally, both expressed
      sequence tag analysis and RT-PCR demonstrated the presence of two differentially
      utilised polyadenylation signals for NAT1 and NAT2, located about 0.2 and 0.3 kb
      downstream of the coding region of each gene.

PMID- 15853927
TI  - Antioxidant properties of carnosine re-evaluated with oxidizing systems involving
      iron and copper ions.
AB  - Carnosine has antioxidant properties and is efficient in the treatment of
      chemically-induced inflammatory lesions in animals. However, some studies
      question its biological significance as antioxidant and show lack of protection
      and even pro-oxidant effect of carnosine in systems containing nickel and iron
      ions. The ability of carnosine to: (1) reduce Fe(3+) into Fe(2+) ions; (2)
      protect deoxyribose from oxidation by Fe(2+)-, Fe(3+)-, and Cu(2+)-H(2)O(2)-EDTA
      systems; (3) protect DNA from damage caused by Cu(2+)-, and Fe(2+)-H(2)O(2)
      ascorbate systems; (4) inhibit HClO- and H(2)O(2)-peroxidase-induced luminol
      dependent chemiluminescence was tested in vitro. At concentration 10 mM carnosine
      reduced 16.6+/-0.5 nmoles of Fe(3+) into Fe(2+) ions during 20 min. incubation
      and added to plasma significantly increased its ferric reducing ability.
      Inhibition of deoxyribose oxidation by 10 mM carnosine reached 56+/-5, 40+/-11
      and 30+/-11% for systems containing Fe(2+), Fe(3+) and Cu(2+) ions, respectively.
      The damage to DNA was decreased by 84+/-9 and 61+/-14% when Cu(2+)-, and Fe(2+)
      H(2)O(2)-ascorbate systems were applied. Combination of 10 mM histidine with
      alanine or histidine alone (but not alanine) enhanced 1.3 and 2.3 times (P<0.05)
      the DNA damage induced by Fe(2+)-H(2)O(2)-ascorbate. These amino acids added to
      10 mM carnosine decreased 3.1-fold (P<0.05) its protective effect on DNA.
      Carnosine at 10 and 20 mM decreased by more than 90% light emission from both
      chemiluminescent systems. It is concluded that carnosine has significant
      antioxidant activity especially in the presence of transition metal ions.
      However, hydrolysis of carnosine with subsequent histidine release may be
      responsible for some pro-oxidant effects.

PMID- 15853928
TI  - Effects of perinatal combined exposure to 1,4-dichlorobenzene and 1,1-dichloro-2,
      2-bis (p-chlorophenyl) ethylene on rat male offspring.
AB  - 1,4-Dichlorobenzene (DCB) is used as an air deodorant or a moth repellent and 1,
      1-dichloro-2, 2-bis (p-chlorophenyl) ethylene (p,p'-DDE) is a persistent
      metabolite of 1, 1, 1-trichloro-2, 2-bis (p-chlorophenyl) ethane (DDT) which was
      used as a pesticide before. DCB concentrations of residential air and oral p,p'
      DDE intake through marine products are demonstrated to be very high in Japan and
      consequently, foetuses and neonates may be exposed much more to DCB and/or p,p'
      DDE via the maternal body. It has recently been reported that DCB is oestrogenic
      and that p,p'-DDE is antiandrogenic. Therefore, the combined effects of perinatal
      exposure to DCB and p,p'-DDE have been investigated in rat male offspring of dams
      ingesting these contaminants during the perinatal period from gestational day 1
      to postpartum day 21 for 42 days. In this study, no obvious developmental effects
      on male offspring have been recognized until 6 weeks of age, following oral
      administration of 25 ppm DCB (approximately 2 mg/kg) and/or 125 ppm p,p'-DDE
      (approximately 10 mg/kg) to dams. In contrast to female offspring, the thymus
      weight in male offspring was not affected by DCB at 6 weeks of age, but there
      might be sexual differences concerning the effects of DCB on the thymus.

PMID- 15853929
TI  - The effect of ciprofloxacin and gentamicin on spinal morphine-induced
      antinociception in rats.
AB  - This paper investigates the possible antinociceptive effect of systemically
      administered ciprofloxacin and gentamicin and its influence on intrathecal
      morphine-induced antinociception. Using thermal nociceptive tests (hot-plate test
      and tail-flick test) and a motor function test (catalepsy test) in male Sprague
      Dawley rats (n=5-9/dose), the following observations were made: ciprofloxacin
      administered intraperitoneally in the dose range 4-64 mg/kg demonstrated a modest
      antinociceptive effect in both nociceptive tests. Solvent of ciprofloxacin
      (intraperitoneally) and saline (intraperitoneally), given as a control, showed no
      effect. Gentamicin, administered at a dose of 0.1-4 mg/kg intraperitoneally,
      demonstrated a significant (P<0.05) antinociceptive effect in the tail-flick test
      but not in the hot-plate test. However, opioid antagonists caused no significant
      change in the antibiotics. Furthermore, ciprofloxacin intraperitoneally produced
      a significant left-shift in the hot-plate test (ED50 saline-morphine=2.86 [CI
      95%: 2.2, 4.32]microg; ED50 ciprofloxacin-morphine=0.87 (CI 95% 0.68, 1.21)
      microg, P<0.05) and in the tail-flick test (ED50 saline-morphine=1.98 (CI 95%:
      1.21, 2.84) microg; ED50 ciprofloxacin-morphine=0.37 (CI 95%: 0.23, 0.44) microg;
      P<0.05) for intrathecal morphine-induced antinociception. From a comparison of
      these data with the predicted ciprofloxacin-morphine value (hot-plate test: 1.61
      (CI 95%: 1.18, 2.51]microg; tail-flick test: 0.82 (CI 95%: 0.52, 1.92) microg) we
      estimate that ciprofloxacin and morphine produce at least additive effects
      (P>0.05). This was reversed with intraperitoneal naloxone (P<0.05). Gentamicin
      intraperitoneally did not influence the antinociception achieved with intrathecal
      administration of morphine (hot-plate test: ED50 gentamicin-morphine=2.71 (CI
      95%: 2.35; 3.2) microg; tail-flick test: ED50 gentamicin-morphine=2.43 (CI 95%:
      1.58; 5.22]microg; P>0.05). These data show that intraperitoneal administration
      of ciprofloxacin and gentamicin produces a modest antinociceptive effect in the
      hot-plate test and tail-flick test. Ciprofloxacin, but not gentamicin, can
      interact at least additively to increased naloxone-reversible morphine
      intrathecal antinociception. Differences in the ability to penetrate the blood
      brain barrier between the two antibiotics could explain the lack of effect from
      gentamicin in the hot plate and on morphine-induced antinociception.

PMID- 15853930
TI  - Resolution of liver fibrosis in chronic CCl4 administration in the rat after
      discontinuation of treatment: effect of silymarin, silibinin, colchicine and
      trimethylcolchicinic acid.
AB  - The purpose of this work was to obtain a suitable model of fibrosis, in which
      spontaneous reversion was minimal, to study the ability of silymarin, silibinin,
      colchicine and trimethylcolchicinic acid (TMCA) to reverse it. Reversal of liver
      fibrosis was studied in male Wistar rats after one, two or three months of CCl(4)
      administration (0.4 g/kg intraperitoneally, three times per week), by
      discontinuation of the toxin for 2 months. Silymarin (50 mg/kg), silibinin (50
      mg/kg), colchicine (10 microg/rat) and trimethylcolchicinic acid (100 microg/rat)
      were administered daily, by gavage, after 3 months of CCl(4) administration.
      Collagen content was determined by measuring hydroxyproline in liver samples;
      glycogen, was determined utilizing the anthrone reagent; Mallory's trichromic
      stains of liver sections were performed. The best scheme of treatment was
      obtained when CCl(4) was administered during three months (collagen increased 6
      times). Discontinuation of the toxin for two months produced a significant but
      relative small reduction of fibrosis (collagen was still 4.5 times over control).
      Colchicine, TMCA, silymarin or silibinin treatment showed no significant
      fibrolitic effect. This scheme of treatment may be an excellent tool to study the
      ability of drugs to reverse fibrosis. The hepatoprotective properties of
      silymarin, silibinin, colchicine and trimethylcolchinic acid may be irrelevant to
      reverse established cirrhosis.

PMID- 15853931
TI  - Effect of local anaesthesia on neuronal c-fos expression in the spinal dorsal
      horn and hypothalamic paraventricular nucleus after surgery in rats.
AB  - The surgical stress response is the neurophysiologic reflex response to surgery,
      which involves activation of the hypothalamic-pituitary-adrenal axis and is
      regulated by the hypothalamic paraventricular nucleus. The effect of pre
      operative use of local anaesthetics on activation of neurones in the
      paraventricular nucleus during surgery was studied by quantification of the
      neuronal expression of the c-fos-gene after a standardized plantar incision in
      rats. Furthermore, c-fos expression in the spinal dorsal horn was used as a
      measure of spinal nociception. Six halothane-anaesthetized animals underwent
      surgery following infiltration with lidocaine and bupivacaine, six animals were
      operated without local anaesthetics, and six control animals were subjected to
      the anaesthetic procedures. After two hours, the animals were perfused with 4%
      formaldehyde and the spinal cords and brains were collected and processed by
      immunohistochemistry for stereological quantification of the number of neurones
      with Fos-like immunoreactivity. Furthermore, brain and spinal cord were sampled
      from nine control animals right after induction of halothane anaesthesia. Surgery
      without local anaesthetics caused a significant increased number of neurones with
      Fos-like immunoreactivity in the spinal cord (4258+/-1710; mean+/-S.D.; P<0.01)
      compared to the anaesthesia control group (1204+/-436). Local anaesthetics
      reduced this number to 2029+/-919 (P<0.05), which was not significantly different
      from the anaesthesia control group. After surgery, the number of neurones with
      Fos-like immunoreactivity in paraventricular nucleus increased from 2948+/-1365
      in the anaesthetized control group to 5550+/-3875 and 5191+/-1558 in the surgery
      and local anaesthetics plus surgery group, respectively, although significance
      was only reached for the group receiving local anaesthetics (P<0.05). In
      conclusion, preoperative local anaesthetic infiltration did not reduce the
      surgery-induced c-fos expression in paraventricular nucleus after paw surgery in
      rats, although spinal nociception was reduced.

PMID- 15853932
TI  - Cost-effectiveness of alendronate in the prevention of osteoporotic fractures in
      Danish women.
AB  - Pharmacological interventions for osteoporosis may reduce morbidity and
      mortality, but they incur additional health care costs. The aim was to quantify
      the additional costs and health benefits of prescribing alendronate 10 mg and
      calcium/vitamin D daily for 71-year-old women with a fracture risk twice that of
      the population average in stead of calcium/vitamin D alone. A state transition
      model based primarily on Scandinavian data was developed. Women were followed
      from age of 71 years until 100. Alendronate was assumed to reduce the fracture
      risk by 50%. Health benefits from the interventions were expressed in terms of
      life years, quality adjusted life years, and fractures avoided. Societal costs
      were estimated using literature estimates and Danish tariffs. All costs were
      measured in 2002 Danish Kroner (DKK). Future costs and benefits were discounted
      at 5% per year. The incremental cost per QALY gained was DKK125,000 while the
      cost per life year gained was DKK 374,000. The use of alendronate was cost-saving
      when 1) the treatment was extended to five years, 2) the risk of fracture was
      four times the population average, 3) the effect of alendronate was assumed to
      persist for three years after discontinuation of treatment, 4) a greater
      proportion had severe sequelae after a hip fracture, or 5) the start of therapy
      was delayed until age of 77 years. In conclusion, the use of alendronate compares
      well with other well established therapies in terms of cost-effectiveness in
      older women with high risk of fracture.

PMID- 15853933
TI  - Organophosphate poisoning in pregnancy: a case report.
AB  - A 42-year-old pregnant woman (26 weeks of gestation, G(4)P(0+3)) presented at the
      emergency department with a two-hour history of dizziness, blurred vision and
      repeated vomiting. These symptoms started during the use of an undiluted
      insecticide liquid (diazinon 60 EC) while cleaning a small non-aired bathroom.
      After clinical and laboratory confirmation for organophosphate poisoning (plasma
      pseudocholinesterase levels 161 U/l), treatment with atropine and pralidoxime was
      started. She recovered within 7 days and delivered a healthy baby 12 weeks later
      (Apgar score 9 and 10) by elective cesarean section. The child showed no signs or
      symptoms of organophospate, atropine or pralidoxime exposure.

PMID- 15853934
TI  - Microbiology of periodontal diseases: introduction.

PMID- 15853935
TI  - Spirochetes at the forefront of periodontal infections.

PMID- 15853936
TI  - Herpesviruses in periodontal diseases.

PMID- 15853937
TI  - Oral microbiology and genomics.

PMID- 15853938
TI  - Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the "red
      complex", a prototype polybacterial pathogenic consortium in periodontitis.

PMID- 15853939
TI  - In vivo induced genes in human diseases.

PMID- 15853940
TI  - Periodontal microbial ecology.

PMID- 15853941
TI  - A Meccano set approach of joining trpzip a water soluble beta-hairpin peptide
      with a didehydrophenylalanine containing hydrophobic helical peptide.
AB  - A 16 residues long, water soluble, monomeric beta-hairpin peptide 'trpzip',
      stabilized by tryptophan zipper has been linked via a tetraglycyl linker to a
      hydrophobic didehydrophenylalnine (DeltaF) containing helical octapeptide.
      Circular dichroism studies of this 28 residues long peptide, 'trpzipalpha' (Ac
      GEWTWDDATKTWTWTE-GGGG-DeltaFALDeltaFALDeltaFA-NH(2)) in water have revealed the
      presence of both the beta-hairpin and the helical conformations. This is the
      first instance where a DeltaF containing peptide has been found to display a
      helical fold in water. The fluorescence emission wavelengths of tryptophan in Ac
      G-W-G-NH(2), trpzip and trpzipalpha were 341.5, 332.8 and 332.6 nm, respectively.
      The fluorescence quantum yield of trpzip was 2.6-fold higher than trpzipalpha
      suggesting that proximal interactions between the beta-hairpin and the helix
      caused the quenching of tryptophan fluorescence in the former by the DeltaFs in
      the latter. The molar ellipticity of the far UV couplet characteristic of trpzip
      was reduced in trpzipalpha and the CD based thermal melting temperatures at 228
      nm were 62 degrees C (trpzip) and 57 degrees C (trpzipalpha). A concentration
      dependent variable temperature CD study in water showed that in trpzipalpha,
      increasing temperature is detrimental to the beta-hairpin, but it augments the
      helical motif, perhaps by intermolecular oligomerization. Our results show that
      in water, trpzipalpha exhibits long-range interactions between two different
      secondary structures. In contrast to trpzip, trpzipalpha has shown a greater
      tendency to oligomerize in water.

PMID- 15853942
TI  - Specific binding of amyloid-beta-protein to IMR-32 neuroblastoma cell membrane.
AB  - In flow cytometry using two detecting methods, we have found that amyloid-beta
      protein(1-40) [Abeta(1-40)] has high affinity to IMR-32 neuroblastoma cell
      membrane when it is aggregated to form beta-sheet conformation, whereas random
      coil small Abeta-species has low affinity. The difference in the binding ability
      to the cell membranes well accounts for the cytotoxicity of Abeta(1-40); namely,
      aggregated beta-sheet Abeta(1-40) gives cytotoxicity higher than random coil
      Abeta(1-40). Specific binding between Abeta(1-40) and ganglioside GM1 of the raft
      like domain in lipid membrane is suggested from a surface plasmon resonance (SPR)
      experiment.

PMID- 15853943
TI  - Interactions of the antimicrobial peptide Ac-FRWWHR-NH(2) with model membrane
      systems and bacterial cells.
AB  - The acetylated and amidated hexapeptide FRWWHR (combi-2), previously identified
      by combinatorial chemistry methods, shows strong antimicrobial activity. The
      binding of the peptide to 1-palmitoyl-2-oleoyl-sn-glycero-3-[(phospho-rac-(1
      glycerol)] (POPG) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)
      vesicles was studied using fluorescence spectroscopy and isothermal titration
      calorimetry (ITC). Differential scanning calorimetry (DSC) with
      dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG)
      multilamellar vesicles was performed to determine changes in the lipid phase
      behaviour upon binding the peptide. Two-dimensional proton nuclear magnetic
      resonance (NMR) spectroscopy, to solve the bound peptide structure, was performed
      in the presence of dodecylphosphatidylcholine (DPC) and sodium dodecyl sulphate
      (SDS) micelles. The fluorescence, ITC and DSC studies indicate that the peptide
      interacts preferentially with lipid vesicles containing negatively charged head
      groups. Conformational information determined using NMR indicate that the combi-2
      peptide adopts a coiled amphipathic conformation when bound to SDS and DPC
      micelles. Leakage assays indicate that the peptide is not very efficient at
      causing leakage from calcein-filled large unilamellar vesicles comprised of
      POPG/POPC (1 : 1). The rapid passage of either the fluorescent-tagged peptides
      combi-2 or the previously studied peptide Ac-RRWWRF-NH(2) (combi-1) into
      Escherichia coli and Staphylococcus aureus suggests that instead of membrane
      disruption, the main bactericidal site of action of these peptides might be
      located inside bacteria.

PMID- 15853944
TI  - Probing the binding of the coumarin drugs using peptide fragments of DNA gyrase B
      protein.
AB  - Bacterial DNA gyrase, has been identified as the target of several antibacterial
      agents, including the coumarin drugs. The coumarins inhibit the gyrase action by
      competitive binding to the ATP-binding site of DNA gyrase B (GyrB) protein. The
      high in vitro inhibitory potency of coumarins against DNA gyrase reactions has
      raised interest in studies on coumarin-gyrase interactions. In this context, a
      series of low-molecular weight peptides, including the coumarin resistance
      determining region of subunit B of Escherichia coli gyrase, has been designed and
      synthesized. The first peptide model was built using the natural fragment 131-146
      of GyrB and was able to bind to novobiocin (K(a) = 1.8 +/- 0.2 x 10(5)/m) and ATP
      (K(a) = 1.9 +/- 0.4 x 10(3)/m). To build the other sequences, changes in the
      Arg(136) residue were introduced so that the binding to the drug was
      progressively reduced with the hydrophobicity of this residue (K(a) = 1.3 +/- 0.1
      x 10(5)/m and 1.0 +/- 0.2 x 10(5)/m for Ser and His, respectively). No binding
      was observed for the change Arg(136) to Leu. In contrast, the binding to ATP was
      not altered, independently of the changes promoted. On the contrary, for peptide
      coumarin and peptide-ATP complexes, Mg(2+) appears to modulate the binding
      process. Our results demonstrate the crucial role of Arg(136) residue for the
      stability of coumarin-gyrase complex as well as suggest a different binding site
      for ATP and in both cases the interactions are mediated by magnesium ions.

PMID- 15853947
TI  - Does childhood immunization against infectious diseases protect from the
      development of atopic disease?
AB  - The argument of whether early immunization against infections promotes allergy or
      protects from it is presently under debate. The relationship between childhood
      immunization and the development of atopic diseases (asthma, allergic rhinitis
      and eczema) was examined in a population-based sample of 718 adolescents by
      taking individual data drawn from personal paediatric records on the schedule and
      the type of vaccination into account. Atopic diseases were determined using a
      standardized questionnaire. After adjustment for sex, age, father's socioeconomic
      status and active smoking, adolescents having been vaccinated (n = 694) had a
      significant lower risk to suffer from asthma or atopic diseases than non
      vaccinated adolescents did (n = 24) [odds ratio (OR) = 0.30; 95% CI: 0.10, 0.92].
      The relationship did not depend on the disease against which the vaccine was used
      as prophylaxis, the observance of the vaccination schedule or the number of
      inoculations. A higher protection was observed in the case of live attenuated
      vaccines (oral poliomyelitis and bacilli Camille-Guerin; OR = 0.26; 95% CI: 0.08,
      0.83). These results, in agreement with previous ecological data, support the
      hypothesis that early vaccines could promote Th1 proliferation in response to the
      infectious agent contained in it, which inhibits the enhancement of atopic
      manifestations. Further studies are needed to confirm the phenomenon.

PMID- 15853948
TI  - Exclusive breastfeeding and risk of atopic dermatitis in some 8300 infants.
AB  - Earlier studies on breastfeeding and atopy in infants have yielded contradictory
      results. We examined the relationship between exclusive breastfeeding and atopic
      dermatitis (AD) in a cohort of infants born between 1 October 1997 and 1 October
      1999 in south-east Sweden. We evaluated the risk of AD 'at least once' or 'at
      least three times' during the first year of life in relation to duration of
      exclusive breastfeeding: <4 months (short exclusive breastfeeding; SEBF) vs. > or
      = 4 months. All data were obtained through questionnaires. Of 8346 infants with
      breastfeeding data, 1943 (23.3%) had suffered from AD during the first year of
      life. Duration of exclusive breastfeeding was not associated with lower risk of
      AD (p = 0.868). SEBF did not influence the risk of any AD (OR = 1.03; 95% CI OR =
      0.91-1.17; p = 0.614) or AD at least three times (OR = 0.97; 95% CI OR = 0.81
      1.16; p = 0.755) during the first year of life. Adjustment for confounders did
      not change these point estimates. Neither was there any link between SEBF and
      risk of AD among infants with a family history of atopy [adjusted odds ratio
      (AOR) = 1.16; 95% CI AOR = 0.90-1.48; p = 0.254]. Furred pets at home were linked
      to a lower risk of AD both among infants with a family history of atopy (AOR =
      0.76; 95% CI AOR = 0.60-0.96; p = 0.021) and among infants with no such history
      (AOR = 0.79; 95% CI AOR = 0.69-0.90; p < 0.001). Infants with no family history
      of atopy were less prone to develop AD if parents smoked (AOR = 0.76; 95% CI AOR
      = 0.61-0.95; p = 0.016). This study indicates that exclusive breastfeeding does
      not influence the risk of AD during the first year of life, while presence of
      furred pets at home seems to be negatively associated with AD.

PMID- 15853949
TI  - Bet v 1-specific IgA increases during the pollen season but not after a single
      allergen challenge in children with birch pollen-induced intermittent allergic
      rhinitis.
AB  - Allergen-specific immunoglobulins of the Immunoglobulin A (IgA) type have been
      found in the nasal fluid of patients with allergic rhinitis. IgA may play a
      protective role, but there are also data which show that allergen-specific IgA
      can induce eosinophil degranulation. The aim of this study was to quantitate Bet
      v 1-specific IgA in relation to total IgA in the nasal fluid of children with
      birch pollen-induced intermittent allergic rhinitis and healthy controls, after
      allergen challenge and during the natural pollen season. Eosinophil cationic
      protein (ECP), Bet v 1-specific IgA and total IgA were analyzed in nasal fluids
      from 30 children with birch pollen-induced intermittent allergic rhinitis and 30
      healthy controls. Samples were taken before the pollen season, after challenge
      with birch pollen and during the pollen season, before and after treatment with
      nasal steroids. During the pollen season, but not after nasal allergen challenge,
      Bet v 1-specific IgA increased in relation to total IgA in children with allergic
      rhinitis. No change was found in the healthy controls. The ratio of Bet v 1
      specific IgA to total IgA increased from 0.1 x 10(-3) (median) to 0.5 x 10(-3) in
      the allergic children, p < 0.001. No change was seen after treatment with nasal
      steroids, although symptoms, ECP and eosinophils were reduced. In conclusion,
      allergen-specific IgA in relation to total IgA increases in nasal fluids during
      the pollen season in allergic children but not in healthy controls. These
      findings are compatible with the hypothesis that allergen-specific IgA plays a
      role in the allergic inflammation and further studies are needed to clarify the
      functional role of these allergen-specific antibodies.

PMID- 15853950
TI  - Time course of antibody response to recombinant Aspergillus fumigatus antigens in
      cystic fibrosis with and without ABPA.
AB  - We determined follow-up levels of specific serum IgE to the recombinant
      Aspergillus fumigatus (A. fumigatus) allergens rAsp f 1, 3, 4 and 6 in patients
      suffering from cystic fibrosis (CF) with and without allergic bronchopulmonary
      aspergillosis (ABPA). Over a 32-month period follow-up data of 74 patients were
      collected. According to serology, 11 CF patients were not sensitized (CF
      controls), 40 were sensitized to A. fumigatus (Asp. f-sens.) and 23 patients
      fulfilled the serologic criteria for ABPA. Of these 23 ABPA patients 11 expressed
      the full clinical ABPA picture (classicABPA) and 12 failed to show sufficient
      relevant clinical signs (seroABPA), despite positive serology. The 23 ABPA
      patients had 16-18 times higher serum levels of specific IgE to rAsp f 4 and/or
      rAsp f 6 than those of Asp. f-sens. patients (rAsp f 4: 31.3 +/- 45 EU/ml vs. 1.9
      +/- 2.2 EU/ml and rAsp f 6: 39.0 +/- 44.3 EU/ml vs 2.1 +/- 1.7 EU/ml). The
      combination of increased total serum IgE (>1000 IU/l) and increased specific IgE
      to rAsp f 4 and/or rAsp f 6 allowed to diagnose classicABPA with 100% specificity
      and 64% sensitivity and with a high predicted positive (100%) and a high
      predicted negative (94%) value. During a combined treatment (seven patients) with
      oral corticosteroid and itraconazole, itraconazole alone (two patients) or
      neither oral corticosteroid nor itraconazole therapy (two patients) total serum
      IgE and specific IgE to rAsp f 4 and/or rAsp f 6 did decrease but did not
      normalize. Over the observation period, lung function remained unchanged,
      independent of whether oral steroids and/or concomitant itraconazole were either
      given or not given. In the follow-up of CF patients with ABPA under therapy the
      determination of total or specific IgE serum levels were of limited value to
      guide therapy.

PMID- 15853951
TI  - Allergies in patients with chromosome 22q11.2 deletion syndrome (DiGeorge
      syndrome/velocardiofacial syndrome) and patients with chronic granulomatous
      disease.
AB  - Humoral immunodeficiencies have a recognized association with atopy. This study
      investigated the association of a T-cell disorder (chromosome 22q11.2 deletion)
      and a neutrophil disorder [chronic granulomatous disease (CGD)] with asthma,
      eczema, and rhinitis using a standardized survey instrument. Patients were
      recruited from either a national referral center (chromosome 22q11.2 deletion
      syndrome) or from a registry (CGD). Controls consisted of siblings of patients.
      Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial
      syndrome) was found to be significantly associated with both eczema and asthma
      but not allergic rhinitis. CGD was not found to be significantly associated with
      atopic diseases.

PMID- 15853952
TI  - Mannose-binding lectin levels in children with asthma.
AB  - Mannose-binding lectin (mbl), one of the important components of innate immunity,
      can activate the lectin pathway of the complement system. After binding mannose
      containing carbohydrate structures of foreign antigen, mbl initiates and
      regulates the inflammatory responses. Asthma is a complex inflammatory disease of
      the lung involving many components of the immune system. Our objective was to
      investigate the serum mbl levels of asthmatic children in comparison with healthy
      controls. Serum mbl levels were determined by nephelometric assay in 72 asthmatic
      children (5-15 yr old) and 30 healthy age-matched controls. Mbl levels of
      asthmatic children were measured both during acute attack and after complete
      remission. There was no significant difference between the mbl levels during
      acute attack (median 4.1 mg/l) or quiescence of symptoms (median 3.6 mg/l). Serum
      mbl levels both during acute attack or quiescence of symptoms was significantly
      higher in asthmatic children than in the healthy controls (median 2.8 mg/l, p <
      0.0001 for each). Furthermore, mbl levels of asthmatic children positively
      correlated with peripheral blood eosinophils (r = 0.377, p < 0.001), which is a
      systemic component of airway inflammation in asthma. Our findings indicate that
      mbl may be implicated in the pathogenesis of asthma by contributing to airway
      inflammation or by increasing the risk of developing asthma.

PMID- 15853953
TI  - Exhaled nitric oxide, total serum IgE and allergic sensitization in childhood
      asthma and allergic rhinitis.
AB  - Exhaled nitric oxide (eNO) levels are correlated with several markers of atopy
      and inflammatory activity in the airways, but the relationship between eNO and
      total serum IgE has not been fully elucidated in the context of allergic
      sensitization. The aim of this study was to investigate the relationship between
      eNO, total serum IgE and allergic sensitization in childhood asthma and allergic
      rhinitis. eNO levels, lung function, skin prick tests and total serum IgE were
      determined in 109 children (mean age, 10.4 yr) with mild intermittent asthma and
      in 41 children (mean age, 10.1 yr) with allergic rhinitis; 25 healthy non-atopic
      children were recruited as controls. eNO levels (median) were significantly
      higher in patients with asthma (22.7 p.p.b.) and in those with allergic rhinitis
      (15.3 p.p.b.) than in healthy controls (5.9 p.p.b.). Children with allergic
      asthma had higher eNO levels than children with allergic rhinitis. A significant
      positive correlation was found between eNO and total serum IgE (asthma, r = 0.42,
      p < 0.0001; allergic rhinitis, r = 0.31, p < 0.01), and between eNO and the
      number of positive skin prick tests (asthma, r = 0.31, p < 0.0001; allergic
      rhinitis, r = 0.39, p < 0.01). eNO levels were better correlated with total IgE
      than with the number of positive skin prick tests. This correlation was
      independent of allergic sensitization. High total serum IgE represents a specific
      and predictive marker of eNO increase in children with asthma or allergic
      rhinitis. This finding adds further support to the hypothesis that increased
      serum IgE could be a marker itself of airway inflammation in patients with
      allergic disease.

PMID- 15853954
TI  - The effect of spirometry and exercise on exhaled nitric oxide in asthmatic
      children.
AB  - American Thoracic Society (ATS) guidelines recommend to refrain from spirometry
      or exercise before measuring fractional exhaled nitric oxide (FENO) because
      forced breathing maneuvers might influence FENO values. However the few studies
      already reported in children have given conflicting results. The aim of the study
      was to observe to what extent spirometry or exercise could affect FENO in
      asthmatic children. Twenty-four asthmatic children (mean age 12.8 yr) were
      enrolled. Measurements of FENO were performed before and 5, 15, 30, 45 and 60 min
      after spirometry or a 6-min walk test, on two separate days in random order.
      Geometric mean FENO at baseline was 25.6 parts per billion (ppb) before
      spirometry and 23.5 ppb before exercise. A small drop of FENO to 24.2 and 23.7
      ppb was found 5 and 15 min after spirometry (both p = 0.04). After exercise, FENO
      values showed a larger drop to 18.5 ppb after 5 min and 20.7 ppb after 15 min (p
      < 0.001; p = 0.004 respectively). Changes in FENO occurred after exercise
      irrespective of baseline FENO and values returned to baseline within 30 min. We
      conclude that both spirometry and exercise affect FENO in asthmatic children. As
      the changes after exercise may lead to erroneous interpretations, children should
      refrain from physical exercise during at least 30 min before FENO measurements.

PMID- 15853955
TI  - Measurement of exhaled nitric oxide in young children during tidal breathing
      through a facemask.
AB  - Measurement of exhaled nitric oxide (eNO) offers a non-invasive means for
      assessment of airway inflammation. The currently available methods are difficult
      to apply in preschool children. We evaluated four methods potentially applicable
      for eNO measurement during tidal breathing in young children. eNO was assessed
      during tidal breathing in 24 children, 2-7 yr old, using a facemask which
      separated nasal and oral airflow. Facemasks with and without a one-way valve
      allowing exhalation through the nose were used. Expiratory flow control was not
      attempted. Measurements of eNO were performed both on-line and off-line. In 11
      children, 8-12 yr old, measurements were compared with the standard single breath
      on-line method. eNO was significantly lower applying the one-way valve in on-line
      and off-line measurements in comparison with measurements without the valve [4.6
      and 3.9 parts per billion (ppb) vs. 6.9 ppb and 6.5 ppb]. The mean within subject
      coefficient of variation (CV) was significantly lower in on-line measurements
      with the one-way valve (9.6%) compared with the other three methods (18.8, 27.7
      and 29.3% respectively). Measurements with a facemask fitted with a one-way valve
      yielded similar eNO levels as the standard single breath method (7.0 ppb vs. 6.9
      ppb) and reproducibility (9.8% vs. 7.1%). In conclusion, reproducible
      measurements of eNO can be obtained without control of expiration flow using a
      facemask fitted with a one-way valve on the nasal compartment. The likely
      explanation to this is that the one-way valve reduces the admixture of nasal NO,
      thereby improving the reliability of eNO measurements.

PMID- 15853956
TI  - Hand-held turbine spirometer: agreement with the conventional spirometer at
      baseline and after exercise.
AB  - Portable hand-held spirometers are widely used in outpatient clinics and in field
      surveys when examining children for asthma. However, the validity of the results
      obtained from the hand-held spirometers has not been assessed in population-based
      studies. We evaluated the agreement between the forced expiratory volume (FEV1)
      values got by the conventional flow volume spirometer (FVS) and the pocket-sized
      turbine spirometer (TS) at baseline and after exercise, among the 212 children
      screened for asthma and asthma-like symptoms from a population of 1633 school
      aged children. The comparison was made between and within three diagnostic
      groups: clinical asthma (n = 34), possible asthma (n = 31), and controls (n =
      147). In general, the differences in FEV1 between the FVS and the TS were small.
      For all children, the mean difference in FEV1 and the limits of agreement
      (difference +/-2 s.d.) was 0.05 l (0.23 to -0.13) at baseline and 0.06 l (0.24 to
      -0.12) after exercise. No significant differences were observed in the agreement
      between the diagnostic groups. In conclusion, although FEV1 results obtained by
      the hand-held spirometer are not interchangeable with those by the conventional
      spirometer, they are in reasonable agreement. The agreement is similar both at
      baseline and after exercise, and is not influenced by the presence of asthma.

PMID- 15853957
TI  - Assessment of use of spacer devices for inhaled drug delivery to asthmatic
      children.
AB  - In the treatment of bronchial asthma, inhaled therapy with both bronchodilators
      and corticosteroids represents the basis for acute and long-term management. Drug
      therapy in asthma is predominantly by pressurized metered dose inhalers. The
      impact of treatment on the disease morbidity and mortality depends to a large
      extent on appropriate delivery of drug to the lungs by means of a spacer device.
      We performed an audit on spacer use in 200 children and showed that 99% owned a
      spacer, 2% owned but did not use their spacer, 11% were using a spacer which was
      not ideal for their age, 17% had a poor technique, and 24% were not following the
      recommendations given on previous visits to wash the spacer only with a soapy
      solution. Although physicians frequently associate poor control of asthma with
      inadequate doses of drugs, many factors must be considered before increasing the
      dose of inhaled medications to children. We should all ensure that the drugs we
      prescribe are delivered in the best possible manner, thus improving control of
      asthma, reducing side effects and offering a more cost-effective therapy.

PMID- 15853958
TI  - Which cereal is a suitable substitute for wheat in children with wheat allergy?
AB  - Wheat is one of the main food allergens. It is among widely used cereals and
      there is an extensive cross-reaction between cereals. The aim of this study is to
      evaluate the extent to which cereals cross-react and to find the best substitute
      for wheat. Eighteen patients with definite diagnosis of type I hypersensitivity
      reactions to wheat enrolled in this study. Measurement of serum-specific IgE and
      skin prick test (SPT) for cereals flour (wheat, barley, oat, rye, rice and corn)
      and wheat bran was carried out. Also, open food challenge tests with available
      and conventional cereals in Iranian food culture (wheat, corn, rice and barley)
      were carried out. The SPTs were positive in 44.4% of patients for barley, 94.5%
      for wheat and 44-77% for other cereals. Positive serum-specific IgE was
      remarkable for wheat and barley and there was correlation between wheat and
      barley-specific IgE concentrations (r = 0.773 and p < 0.01). Corn serum-specific
      IgE was measured in 10 patients, which were positive in six of them. Of the
      patients, 55.5% had positive barley challenge tests, but all corn and rice
      challenge tests were negative. The best substitutes for wheat in wheat allergic
      patients are rice and corn. Regarding the correlation of wheat and barley serum
      specific IgEs, there might be a high antigenic cross-reaction, therefore barley
      is not a good substitute for wheat and consuming barley needs a careful challenge
      test. Considering concordance of positive SPT to wheat flour and wheat bran,
      avoiding both of them is necessary in patients with wheat allergy.

PMID- 15853959
TI  - Levocetirizine in children: evidenced efficacy and safety in a 6-week randomized
      seasonal allergic rhinitis trial.
AB  - Studies evaluating newer antihistamines in children are few. Levocetirizine is a
      potent and highly selective H1-antihistamine with a proven efficacy in adults.
      Primary objective was to assess the efficacy of levocetirizine 5 mg once-daily in
      reducing seasonal allergic rhinitis (SAR) symptoms, as measured by Total Four
      Symptom Score (T4SS = sum of sneezing, rhinorrhea, nasal and ocular pruritus),
      over the first 2 wk of treatment. Efficacy over 4 and 6 wk of treatment, effect
      on nasal congestion and on health-related quality of life as measured by PRQLQ
      (Paediatric Rhinoconjunctivitis Quality of Life Questionnaire) were among the
      major secondary objectives. A double-blind, randomized, placebo-controlled study
      including 177 children with a documented SAR (to grass and/or weed) for at least
      a year and having a mean baseline T4SS > or = 6 (out of 12). Children evaluated
      daily the severity of T4SS and nasal congestion on a scale from 0 (absent) to 3
      (severe). PRQLQ responses were assessed on a scale from 0 (not bothered) to 6
      (extremely bothered) and analysed descriptively. Global evaluation of disease
      evolution judged by investigators, parents and children was made on a scale from
      1 (marked worsening) to 7 (marked improvement). For the primary objective,
      levocetirizine was statistically highly superior to placebo with a difference in
      adjusted means of 1.29 (95% CI: 0.66-1.92) in favour of levocetirizine (p <
      0.001). The effect of levocetirizine was almost twice that of placebo (94.1%
      relative improvement over placebo). Nasal congestion was improved with
      levocetirizine reaching maximum difference to placebo of 0.31 (p < 0.05), a
      relative improvement over placebo of 77.5%. PRQLQ scores at week 2 improved with
      levocetirizine more than with placebo (0.85 vs. 0.51, respectively) remaining
      larger after 4 and 6 wk of treatment. In the study, 84.3%, 80.9%, 80.9% of
      children had their disease evolution rated as slightly-to-markedly improved by,
      respectively, the investigators, the parents and children themselves. Incidence
      of treatment-emergent adverse events was similar in both groups (33.7% with
      levocetirizine; 30.7% with placebo). No child in the levocetirizine group
      discontinued treatment because of adverse events. The 6-wk duration of this study
      was longer than the usual 2-4-wk duration for similar studies and shows that
      levocetirizine controls SAR symptoms in children over the entire pollen season.

PMID- 15853960
TI  - Analysis of tracheal secretions for rhinovirus during natural colds.
AB  - Rhinoviruses (RV) cause 50% of common colds and are frequently isolated from
      children and adults hospitalized for asthma exacerbations. Although colds may
      trigger severe coughing and wheezing, it is not known whether these symptoms are
      a result of lower airway infection with RV. Previous efforts to address this
      question by sampling lower airway secretions during experimental RV infections
      have been complicated by the possibility of contamination of the bronchoscope
      with nasopharyngeal cells and secretions. To further test the hypothesis that RV
      infections involve the lower airways, tracheal and nasal secretions were obtained
      from 23 pediatric tracheostomy patients, including seven with cold symptoms and
      16 asymptomatic controls. RV was detected by reverse-transcription polymerase
      chain reaction from the nasal and tracheal secretions of three of the seven
      children with cold symptoms. In the 16 well children, RV was not detected in any
      samples of nasal secretions, but was isolated from four samples of tracheal
      secretions. These results demonstrate the presence of RV in the lower airways of
      children with tracheostomies during community-acquired colds, without the
      possibility of nasal contamination. In addition, these findings suggest that
      children with tracheostomies carry subclinical viral infections in their
      tracheas, rather than their noses.

PMID- 15853961
TI  - Alloimmune neonatal neutropenia and thrombocytopenia associated with maternal
      anti HNA-1a, HPA-3b and HLA antibodies.
AB  - The incidence of alloimmune neonatal neutropenia combined with neonatal
      alloimmune thrombocytopenia is very low. We report a case of a neonate who
      suffered severe neutropenia and thombocytopenia with widespread petechial spots.
      The presence of alloantibodies in mother's and patient's sera was analyzed by
      lymphocytotoxicity test, agglutination test, granulocyte indirect
      immunofluorescence test, platelet immunofluorescence test (PIFT) and solid phase
      enzyme-linked immunosorbent assay. Human neutrophil antigens (HNA) and human
      platelet antigen (HPA) genotypes were tested by polymerase chain reaction
      analyses. The mother's and patient's sera reacted with neutrophils and
      lymphocytes of the father. PIFT revealed the presence of IgG anti-platelet
      antibodies in the patient's serum but the test was negative in the maternal
      serum. Analyses of HNA-1 and HPA genotypes of the family revealed maternal
      neonatal HNA-1a and HPA-3b mismatch. The study of the mother's and patient's sera
      showed the presence of anti HNA1a, HPA-3b and HLA antibodies specific for HLA-A3
      and HLA-B38 antigens. These results suggest that the transplacental passage of
      maternal HNA-1a, HPA-3b and HLA alloantibodies caused neutropenia and
      thrombocytopenia in this patient.

PMID- 15853962
TI  - Does the severity of atopic dermatitis correlate with serum IgE levels?

PMID- 15853963
TI  - Sequence variations in rgpA and rgpB of Porphyromonas gingivalis in
      periodontitis.
AB  - OBJECTIVE: The aim of the present study was to determine sequence variations in
      the active centre of the Arg-X-specific protease encoding genes rgpA and rgpB of
      clinical Porphyromonas gingivalis isolates and to analyse their prevalence in
      periodontitis patients before and 3 months after mechanical periodontal therapy.
      BACKGROUND: Genetic diversity at nucleotides 281, 283, 286 and 331 has been shown
      to result in amino acid substitutions in the catalytic domain of RgpA and RgpB
      that affect the substrate specificity and thus may influence the efficacy of Arg
      X-protease specific inhibitors. METHODS: Sequence analysis of rgpA and rgpB genes
      in clinical P. gingivalis strains isolated from subgingival plaque samples of 82
      periodontitis patients before and 3 months after mechanical supra- and
      subgingival debridement was performed. RESULTS: No specific variation within the
      rgpA sequence was observed. However, the rgpB sequence in the region of the
      active centre showed five different rgpB genotypes, which were named NYPN, NSSN,
      NSSK, NYPK and DYPN according to the derived amino acid substitution.
      Porphyromonas gingivalis genotype NYPN was detected in 27 patients (32.9%) before
      and in 8 patients (9.8%) after therapy, NSSN in 26 (31.7%) and 10 (12.2%), NSSK
      in 22 (26.8%) and 2 (2.4%), NYPK in 5 (6.2%) and 1 (1.2%), and DYPN in 1 patient
      (1.2%) and 0 patients (0%), respectively. Only one patient (1.2%) harboured two
      P. gingivalis rgpB genotypes (NSSK/NYPN) before treatment; these were no longer
      detected after therapy. CONCLUSION: The results indicate that five rgpB genotypes
      are maintained in natural populations of P. gingivalis. These data may be of
      importance with regard to the development of specific rgpB inhibitors.

PMID- 15853964
TI  - Longitudinal analysis of metalloproteinases, tissue inhibitors of
      metalloproteinases and clinical parameters in gingival crevicular fluid from
      periodontitis-affected patients.
AB  - BACKGROUND: The aim of this work was to improve the assessment of the periodontal
      disease status through measurements of extracellular matrix metalloproteinases
      (MMPs) and their tissular inhibitors (TIMPs) in the gingival crevicular fluid
      from patients diagnosed with chronic periodontitis. METHODS: Gingival crevicular
      fluid samples from patients (n = 13) were taken from 60 sites initially, and from
      51 and 41 sites, respectively, 3 and 6 months after scaling and root planing.
      Gingival crevicular fluid samples were also taken from healthy subjects (n = 11,
      24 sites). The presence of MMP-9 and MMP-8 was assessed by zymography and
      immunowestern blotting, respectively. The actual MMP activity (gelatinase and
      collagenase) was measured using the fluorogenic substrate assay. TIMP-1 and -2
      levels were measured by immunodot blot. RESULTS: The fluorogenic substrate assay
      determinations showed higher MMP activity in sites with probing depth > or = 4
      mm, with significant reduction post-treatment. Gelatinase activity followed by
      zymography consisted mainly of MMP-9. A different pattern of MMP-8 in control and
      patient sites was found. Controls only showed species of a partially active form
      (69 kDa), whereas patient sites showed a high frequency of the active form (56
      kDa), and in some cases the latent form (85 kDa) was also observed. The active
      form reduced its frequency in sites with probing depth > or = 4 mm. TIMP-1 and -2
      levels in patients were significantly lower than in controls, and after treatment
      the recovery of TIMP-1 level similar to control was observed. CONCLUSION:
      Significant correlations between the severity of the periodontal disease and the
      actual MMP activity, the active form of MMP-8 and the low level of both TIMP-1
      and TIMP-2 were found.

PMID- 15853965
TI  - Protective effects of etoricoxib, a selective inhibitor of cyclooxygenase-2, in
      experimental periodontitis in rats.
AB  - BACKGROUND: The purpose of the present study was to evaluate the effect of a
      potent selective cyclooxygenase-2 (COX-2) inhibitor, etoricoxib, on the
      prevention of alveolar bone loss in experimental periodontitis induced in rats.
      METHODS: Ninety Wistar rats were separated into three experimental groups. Cotton
      ligatures were placed at the gingival margin level of lower right first molars.
      The rats were randomly assigned to one of the following groups: control received
      a daily oral dose of 1 ml/kg of saline solution; Eto1 received 6 mg/kg of
      etoricoxib; Eto2 received 12 mg/kg of etoricoxib. Serum levels of etoricoxib and
      white blood cells were determined. Standardized digital radiographs were taken
      after death at 3, 5, 10, 18 and 30 days to measure the amount of bone loss at the
      mesial root surface of the first molar tooth in each rat. RESULTS: One-way
      analysis of variance (anova) indicated that groups treated with both doses of
      etoricoxib had significantly (p < 0.05) less alveolar bone loss when compared to
      controls. Furthermore, etoricoxib treatment significantly inhibited the
      leukocytosis observed 3 days after the induction of periodontitis. CONCLUSION:
      These data provide evidence that systemic therapy with etoricoxib can retard
      alveolar bone loss in a ligature-induced periodontitis model in rats.

PMID- 15853966
TI  - The effect of spironolactone on experimental periodontitis in rats.
AB  - BACKGROUND: Elevated levels of tumour necrosis factor (TNF) have been found in
      patients with adult periodontitis. Animal studies have shown that TNF plays an
      important role in the pathogenesis of periodontitis. New findings suggest that
      the aldosterone-inhibitor spironolactone possesses an anti-TNF effect. The
      purpose of the study was to determine the anti-TNF effect of spironolactone in an
      endotoxic shock rat model and to disclose the effect of oral administration of
      spironolactone on the development of experimental periodontitis in rats. METHODS:
      The study was divided in two parts. Part 1: oral administration of spironolactone
      (100 mg/kg) followed by intravenous lipopolysaccharide (1 mg/kg) infusion 45 min
      later. Blood samples were taken before and 90 min after lipopolysaccharide
      infusion to determine the TNF levels in spironolactone treated and non-treated
      rats. Part 2: oral administration of spironolactone [100 mg/(kg day)] starting 2
      days prior to induction of experimental periodontitis established by peridental
      ligatures. Morphometrical and radiographical registrations of alveolar bone
      destruction were carried out to determine the effect of spironolactone on the
      progression of experimental periodontitis. RESULTS: In part 1 the endotoxic shock
      model showed a significant reduction in TNF levels in the spironolactone-treated
      group compared to the non-treated group, suggesting that spironolactone acts as a
      TNF inhibitor. In part 2 spironolactone-treated rats did not demonstrate
      significantly less alveolar bone destruction compared to non-treated rats.
      CONCLUSIONS: The insignificant effect of spironolactone treatment could be
      explained by the fast metabolism of spironolactone and that spironolactone does
      not completely inhibit TNF production in rats. Moreover, many other cytokines and
      mediators involved in alveolar bone destruction may account for the lacking
      response to spironolactone.

PMID- 15853967
TI  - Cyclosporin A promotes mineralization by human cementoblastoma-derived cells in
      culture.
AB  - OBJECTIVE: The immunosuppressive drug cyclosporin A has been shown to induce
      cementum deposition in vivo in experimental animals. Using cementoblastoma
      derived cells, we have studied whether this drug will be useful to study cementum
      mineralization and differentiation in vitro. METHODS: Human cementoblastoma cells
      and gingival fibroblasts (controls) were cultured and treated with 0.5, 1.0 and
      5.0 microg/ml of cyclosporin A. Cell proliferation was evaluated by MTT
      (tetrazolium) assay and cell number, and cell viability was assessed by trypan
      blue dye exclusion. Induction of mineralization was evaluated by alizarin red S
      staining to detect mineralized nodules and by reverse transcription-polymerase
      chain reaction (RT-PCR) to assess the expression of bone differentiation markers
      alkaline phosphatase, osteocalcin, bone sialoprotein and core-binding factor a1
      (Cbfa1). RESULTS: Cyclosporin A at 5.0 microg/ml concentration reduced
      significantly the increase in the number of cementoblastoma cells. A dose
      dependent increase in the number of mineralized nodules occurred in cultures of
      cementoblastoma-derived cells treated with cyclosporin A, and RT-PCR analyses
      showed significantly higher levels of expression of alkaline phosphatase, bone
      sialoprotein, type I collagen, matrix metalloproteinase-1, osteocalcin,
      osteopontin, and Cbfa1. Human gingival fibroblast proliferation and cell number
      were not affected. Mineralized nodules were not detected in gingival fibroblasts
      and bone specific proteins were not expressed. CONCLUSIONS: Presence of
      cyclosporin A during 14-day culture period appears to suppress the proliferation
      of cementoblastoma cells and induce the formation mineralized-like tissue by
      these cells.

PMID- 15853968
TI  - An in vitro model of chlorhexidine-induced tooth staining.
AB  - BACKGROUND: Tooth staining is a common feature of chlorhexidine treatment for
      periodontal disease and there is a large variation between patients as to the
      degree of their tooth staining. Although the mechanism of tooth staining is
      uncertain, diet, smoking and oral hygiene appear probable factors. OBJECTIVES:
      This study investigated the role of saliva in chlorhexidine-induced tooth
      staining and used tea as the staining agent in an in vitro model with
      hydroxyapatite mimicking teeth. METHODS: Saliva has been used to create an
      acquired pellicle and in solution to mimic its effects in vivo. Using different
      combinations of tea, chlorhexidine and parotid saliva, substances binding to
      hydroxyapatite were analysed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. Using this system, tea, chlorhexidine and salivary proteins were
      clearly identifiable following staining by Coomassie Brilliant Blue. RESULTS: The
      results indicated that tea interacted with many salivary proteins, in particular
      proline-rich proteins and histatins. Chlorhexidine did not appear to complex with
      or precipitate salivary proteins nor prevent the formation of an acquired
      pellicle on the hydroxyapatite. In isolation, tea and chlorhexidine bound in
      small amounts to hydroxyapatite, but when added in combination, binding of both
      to hydroxyapatite was greatly increased. The acquired pellicle reduced
      chlorhexidine and tea binding, but conversely increased the binding of either tea
      or chlorhexidine alone to hydroxyapatite. CONCLUSION: In conclusion, salivary
      proteins play an important role in the staining process and the combination of
      tea and chlorhexidine appears to be a very potent staining factor.

PMID- 15853969
TI  - Marker of cemento-periodontal ligament junction associated with periodontal
      regeneration.
AB  - OBJECTIVE: The purpose of this study was to identify factors promoting formation
      of the cemento-periodontal ligament junction. BACKGROUND: Regeneration of the
      cemento-periodontal ligament junction is an important factor in recovery of the
      connective tissue attachment to the cementum and it is important to identify all
      specific substances that promote its formation. To clarify the substances
      involved in cemento-periodontal ligament junction formation, we produced a
      monoclonal antibody (mAb) to human cemento-periodontal ligament junction
      (designated as the anti-TAP mAb) and examined its immunostaining properties and
      reactive antigen. METHODS: Hybridomas producing monoclonal antibody against human
      cemento-periodontal ligament junction antigens were established by fusing P3U1
      mouse myeloma cells with spleen cells from BALB/c mice immunized with homogenized
      human cemento-periodontal ligament junction. The mAb, the anti-TAP mAb for
      cemento-periodontal ligament junction, was then isolated. The immunoglobulin
      class and light chain of the mAb were examined using an isotyping kit. Before
      immunostaining, antigen determination using an enzymatic method or heating was
      conducted. Human teeth, hard tissue-forming lesions, and animal tissues were
      immunostained by the anti-TAP mAb. RESULTS: The anti-TAP mAb was positive in
      human cemento-periodontal ligament junction and predentin but negative in all
      other human and animal tissues examined. In the cemento-osseous lesions, the anti
      TAP mAb was positive in the peripheral area of the cementum and cementum-like
      hard tissues and not in the bone and bone-like tissues. The anti-TAP mAb showed
      IgM (kappa) and recognized phosphoprotein. CONCLUSION: The anti-TAP mAb is
      potentially useful for developing new agents promoting cementogenesis and
      periodontal regeneration.

PMID- 15853970
TI  - Variance components of gingival thickness.
AB  - OBJECTIVES: Distinct periodontal phenotypes have been identified by cluster
      analysis, which is an explorative method with very low external validity. The aim
      of the present study was to investigate variance components of facial gingival
      thickness in young adults with mild gingivitis. MATERIAL AND METHODS: Thirty
      three non-smoking females, 18-23 years of age, with mild or moderate plaque
      induced gingivitis participated. Gingival thickness was measured at every tooth
      present by use of ultrasound technology to the next 0.1 mm with a lowest
      measurement of 0.5 mm. Periodontal probing depth and clinical attachment level
      were measured with a pressure-controlled probe. Gingival bleeding index was
      assessed after probing on a 0-2 scale, where 1 was slight, and 2 was profuse
      bleeding on probing. The Silness-Loe plaque index was recorded. Multilevel
      variance components and random intercept models were built. RESULTS: A 2-level
      (subject, tooth) variance component model of gingival thickness without any
      explanatory variable revealed an intercept (mean) of 0.93 +/- 0.02 mm. Subject
      variation of gingival thickness amounted to 4.2% of the total variance. Addition
      of tooth- and subject-related covariates to the model revealed, after adjusting
      for tooth type, an association with periodontal probing depth (estimated
      coefficient 0.067 +/- 0.025), and considerable association with average bleeding
      index (-0.395 +/- 0.149) and plaque index (0.125 +/- 0.048). Variation at the
      tooth level was drastically reduced; subject variation amounted to 5.2%.
      CONCLUSION: Gingival thickness is mainly associated with tooth-related variables.
      Bleeding tendency is higher if gingiva is thin. Subject variability related to
      periodontal phenotype may add to the total variance, however, to a very low
      extent.

PMID- 15853971
TI  - Application of periodontal ligament cell sheet for periodontal regeneration: a
      pilot study in beagle dogs.
AB  - OBJECTIVE: The ultimate goal of periodontal treatment is to regenerate the
      damaged periodontal support. Although periodontal ligament (PDL) cells are
      essential for periodontal regeneration, few studies have reported the
      transplantation of periodontal ligament cells to periodontal defects. We
      developed a new method to apply periodontal ligament cells as a sheet to the
      defect. The aim of this study was to investigate the periodontal healing after
      application of the periodontal ligament cell sheet in beagle dogs. METHODS:
      Autologous periodontal ligament cells were obtained from extracted premolars of
      each beagle dog. Periodontal ligament cell sheets were fabricated using a
      temperature-responsive cell culture dish. Dehiscence defects were surgically
      created on the buccal surface of the mesial roots of bilateral mandibular first
      molars of each dog. In the experimental group (five defects), periodontal
      ligament cell sheet with reinforced hyaluronic acid carrier was applied to the
      defect. Only the hyaluronic acid carrier was applied to the contralateral side as
      a control (five defects). Eight weeks after surgery, the animals were sacrificed
      and decalcified specimens were prepared. Healing of the periodontal defects was
      evaluated histologically and histometrically. RESULTS: No clinical signs of
      inflammation or recession of gingiva were observed in both experimental and
      control groups. In the experimental group, periodontal tissue healing with bone,
      periodontal ligament and cementum formation was observed in three out of five
      defects. In the control group, such periodontal tissue formation was not observed
      except in one defect. Histometric analysis revealed that the formation of new
      cementum in the experimental group was significantly higher than that in the
      control group. CONCLUSION: The periodontal ligament cell sheet has a potential to
      regenerate periodontal tissue and may become a novel regenerative therapy.

PMID- 15853972
TI  - The up-regulation of heme oxygenase-1 expression in human gingival fibroblasts
      stimulated with nicotine.
AB  - BACKGROUND: Cigarette smoking is a major risk factor in the development and
      further progression of periodontal diseases. Heme oxygenase-1 (HO-1) is known as
      a stress-inducible protein and functions as an antioxidant enzyme. There is
      limited information on the expression of HO-1 in smoking-associated periodontal
      disease. OBJECTIVES: The aim of the present study was to investigate the effects
      of nicotine on the expression of HO-1 protein in cultured human gingival
      fibroblasts in vitro and further to compare HO-1 expression in gingival tissues
      obtained from cigarette smokers and non-smokers in vivo. METHODS: Western blot
      assay was used to investigate the effects on human gingival fibroblasts exposed
      to nicotine. In addition, antioxidants catalase, superoxide dismutase (SOD), and
      N-acetyl-l-cysteine (NAC) were added to test how they modulated the effects on
      nicotine-induced HO-1 expression. Gingival biopsies taken from the flap surgery
      of 20 male patients with periodontal disease (10 cigarette smokers and 10 non
      smokers) were examined by immunohistochemistry. RESULTS: The exposure of
      quiescent human gingival fibroblasts to 10 mm nicotine resulted in the induction
      of HO-1 protein expression in a time-dependent manner (p < 0.05). The addition of
      glutathione (GSH) precursor NAC inhibited the nicotine-induced HO-1 protein
      expression (p < 0.05). However, SOD and catalase did not decrease the nicotine
      induced HO-1 protein expression (p > 0.05). The results from immunohistochemistry
      demonstrated that HO-1 expression was significantly higher in cigarette smokers
      (p < 0.05). HO-1 was noted in the basal layers of epithelium, inflammatory cells,
      and fibroblasts in specimens from cigarette smoking. CONCLUSIONS: Taken together,
      these results suggest that HO-1 expression is significantly up-regulated in
      gingival tissues from cigarette smokers, and nicotine may, among other
      constituents, be responsible for the enhanced HO-1 expression in vivo. The
      regulation of HO-1 expression induced by nicotine is critically dependent on the
      intracellular GSH concentration.

PMID- 15853973
TI  - Characterization of Actinobacillus actinomycetemcomitans isolated from young
      Chinese aggressive periodontitis patients.
AB  - OBJECTIVE: This study characterized Actinobacillus actinomycetemcomitans isolates
      from young Chinese aggressive periodontitis patients. METHODS: Subgingival plaque
      samples (two/subject) were collected from diseased subjects < 25 years old (n =
      9, mean age 21.1 +/- 1.6 years) and age-matched periodontitis-free controls (n =
      47, mean age 22.0 +/- 1.1 years). Selective and anaerobic culture were used. The
      serotype, leukotoxin gene (ltx) operon promoter and the cytolethal distending
      toxin (cdt) genes complex of the A. actinomycetemcomitans isolates were
      investigated. Effects of the isolates on non-keratinizing periodontal ligament
      epithelial cells monolayer were studied. RESULTS: Diseased subjects had
      significantly higher full-mouth bleeding score (p = 0.002) and total viable
      counts from plaque samples (7.2 x 10(6) vs. 2.1 x 10(5) CFU/paperpoint, p <
      0.005). A. actinomycetemcomitans was isolated from 67%/56% or 6%/4% of diseased
      or controls subject/sites, respectively (p < 0.001). The proportion of A.
      actinomycetemcomitans isolatable from aggressive periodontitis or periodontitis
      free associated subgingival plaque was low (0.7% vs. 0.1%, p < 0.02). The
      serotype of the isolates was characterized. All isolates possessed 652-like ltx
      gene promoter and all but one serotype c isolate from a diseased patient had
      intact cdtABC genes. That particular strain appeared to confer the least cellular
      damages on periodontal ligament epithelial monolayer compared to others.
      CONCLUSION: This preliminary study confirmed the notion of increased prevalence
      and quantity of A. actinomycetemcomitans associated with aggressive periodontitis
      in young patients. The overall ltx promoter and cdt characteristics of the A.
      actinomycetemcomitans isolates, however, were similar among the diseased and
      control groups. A strain lacking the cdtABC gene appeared to be less damaging to
      a periodontal ligament epithelial cell model. Further studies therefore are
      warranted to clarify the pathogenic role and potentials of A.
      actinomycetemcomitans in aggressive periodontitis.

PMID- 15853974
TI  - Three-dimensional evaluation for augmented bone using guided bone regeneration.
AB  - OBJECTIVE: This study evaluated new bone regeneration beyond the skeletal
      envelope within an occlusive titanium cap on rabbit calvaria using microfocus
      computed tomography images. METHODS: In 10 rabbits, the calvaria was exposed and
      a circular groove was prepared. After penetrating the marrow, a standard
      hemispherical titanium cap was placed in the groove and covered with a cutaneous
      flap. After 1 or 3 months, the animals were killed and the calvariae and titanium
      caps were dissected. After taking microfocus computed tomography images of the
      specimens, histological sections were made. The specimens were observed using
      three-dimensional images constructed from the microfocus computed tomography
      images, and the histological sections were examined to compute bone parameters.
      RESULTS: The three-dimensional images and histological specimens showed that new
      bone formed in flat, cup-like, and dome shapes. The bone parameters trabecular
      thickness and the proportion of marrow space to the capacity of the titanium cap
      increased, whereas bone density decreased, and there were significant differences
      between the 1- and 3-month groups. DISCUSSION: First, a cylinder of new bone
      formed from the existing bone. Gradually, bone formed along the cap wall and the
      new tissue formed in a crater indented centrally. Finally, the new tissue formed
      in the shape of a dome. CONCLUSION: Trabecular bone formed along the wall of the
      titanium cap, and bone filled the inside of the cap within 3 months.

PMID- 15853975
TI  - Molecular analysis of human oral microbiota.
AB  - OBJECTIVES: The application of molecular, mainly 16S ribosomal RNA (rRNA)-based
      approaches enables researchers to bypass the cultivation step and has proven its
      usefulness in studying the microbial composition in a variety of ecosystems,
      including the human oral cavity. In this mini-review, we describe the impact of
      these culture-independent approaches on our knowledge of the ecology of the human
      oral cavity and provide directions for future studies that should emphasize the
      role of specific strains, species and groups of microbes in periodontal disease.
      MATERIALS AND METHODS: Recent findings are summarized to elucidate the
      relationship between periodontal disease and human oral microbiota, including as
      yet-to-be-cultured organisms. RESULTS: The real-time polymerase chain reaction
      (PCR) method was developed to detect and quantify periodontopathic bacteria, such
      as Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella
      intermedia, Tannerella forsythensis (formerly Bacteroides forsythus) and
      Treponema denticola. The checkerboard DNA-DNA hybridization technique allowed
      enumeration of large numbers of species in very large numbers of samples. 16S
      rRNA gene clone library analysis revealed the diversity of human oral microbiota
      and the existence of as-yet-to-be-cultured organisms that are presumed
      periodontal pathogens. In addition, terminal restriction fragment length
      polymorphism (T-RFLP) analysis was applied for assessment of diversity of human
      oral microbiota. CONCLUSION: Culture-independent approaches are useful for
      studying the microbial ecology in the human oral cavity and should be useful in
      the future to elucidate the etiology of periodontal disease.

PMID- 15853976
TI  - Dual hepatitis B virus and hepatitis C virus infection: To treat or not to treat,
      and how?

PMID- 15853977
TI  - Agenesis of the gallbladder: difficulties in management.
AB  - Gallbladder agenesis is a rare congenital biliary anomaly that may be associated
      with other biliary and extrabiliary congenital anomalies. Awareness of this
      entity by clinicians and radiologists is essential because many of these patients
      present with biliary symptoms and have unnecessary operations. In the present
      article, the relative epidemiological, etiological (embryology and development),
      pathophysiological, diagnostic tools and pitfalls and management aspects of this
      rare anatomic anomaly are briefly discussed through review of the literature.
      Particular reference to the difficulty in preoperative diagnosis is highlighted.
      The importance of the possibility of preoperative diagnosis to avoid unnecessary
      surgery is stressed.

PMID- 15853978
TI  - Carcinoid of the ampulla of Vater.
AB  - Endocrine neoplasms only rarely occur at the ampulla of Vater, comprising mostly
      carcinoids and malignant carcinoids, as well as few cases of poorly
      differentiated endocrine carcinomas (small cell carcinomas). Only 105 cases are
      reported in the literature, most as single case reports. For many years, the
      neoplasms of the disseminated neuroendocrine cell system of the gastrointestinal
      tract have been subsumed as 'carcinoids'. Instead, in the latest World Health
      Organization (WHO) classification published in 2000, it is recommended to
      distinguish between (i) well-differentiated endocrine tumors (carcinoids); (ii)
      well-differentiated endocrine carcinomas (malignant carcinoids); and (iii) poorly
      differentiated endocrine carcinomas (small cell carcinomas). Patients with
      carcinoid tumors of the ampulla of Vater are very often free of clinical and
      laboratory findings that belong to the carcinoid syndrome. Approximately 26% of
      all patients with carcinoid tumor reported in the literature had
      neurofibromatosis. Besides endoscopic retrograde cholangiopancreatography,
      endosonography, computed tomography or magnetic resonance imaging may complete
      the staging approach of this tumor. The Kausch-Whipple procedure or pylorus
      preserving pancreaticoduodenectomy is considered the treatment of choice for
      ampullary, well-differentiated carcinoids >2.0 cm and for ampullary
      neuroendocrine carcinomas. However, it should be considered that long-term
      survival of patients with ampullary carcinoids is also reported after local tumor
      excision (5-year survival rate of 90%). The dilemma is that the differentiation
      of neuroendocrine tumors cannot be assessed intraoperatively in most cases.
      Therefore, considering that the 5-year survival rate in patients with
      neuroendocrine carcinomas of the ampulla of Vater is very low without radical
      resection, neuroendocrine tumors of the ampulla of Vater without definite
      histological differentiation should undergo extended surgery.

PMID- 15853979
TI  - Characteristics of gastritis in patients with Helicobacter pylori-positive reflux
      esophagitis.
AB  - BACKGROUND AND AIM: The influence of Helicobacter pylori on gastric acid
      secretion differs with the status of gastritis. The histological characteristics
      of gastritis in H. pylori-positive patients with reflux esophagitis have not been
      fully investigated. We therefore studied the pattern of endoscopic gastric
      mucosal atrophy and degree of histological gastritis in such patients. METHODS:
      Subjects comprised 41 H. pylori-positive patients with reflux esophagitis, 41 age
      and sex-matched patients with duodenal ulcer, and 41 patients with early gastric
      cancer. The endoscopic pattern of gastric mucosal atrophy was reviewed, and the
      degree of histological gastritis in biopsy specimens from the antrum and corpus
      was assessed in accordance with the updated Sydney system. RESULTS: The grade of
      endoscopic and histological gastric mucosal atrophy in patients with reflux
      esophagitis was significantly lower than that in patients with gastric cancer,
      and the histological scores for antral atrophy and metaplasia in patients with
      reflux esophagitis tended to be lower than those in patients with duodenal ulcer.
      In patients with reflux esophagitis and duodenal ulcer, the scores for antral
      inflammation and activity tended to be higher than those for the corpus.
      Conversely, the inflammation and activity score in patients with early gastric
      cancer showed a corpus-predominant gastritis pattern. CONCLUSION: In H. pylori
      positive patients with reflux esophagitis, the degree of endoscopic gastric
      mucosal atrophy is low and histologically there is an antral-predominant
      gastritis pattern. Therefore, gastric acid secretion in H. pylori-positive
      patients with reflux esophagitis may be augmented by H. pylori infection.

PMID- 15853980
TI  - Segmental colonoscopic biopsies in the differentiation of ileocolic tuberculosis
      from Crohn's disease.
AB  - BACKGROUND AND AIM: The differentiation between Crohn's disease (CD) and
      tuberculosis (TB) of the intestine can be difficult in areas where both diseases
      occur. The present study examined histological criteria that would enable the
      diagnosis in mucosal biopsies. METHODS: Colonoscopic biopsies from 33 patients
      with TB and 31 patients with CD were examined for several specific histological
      features and their distribution. RESULTS: The salient distinguishing features of
      TB were granulomas larger than 400 microm in maximum dimension, more than four
      sites of granulomatous inflammation per site, cessation, a band of epithelioid
      histiocytes in ulcer bases and location of granulomas in the caecum. The salient
      features of CD were granulomas not showing any of the above features, focally
      enhanced colitis, pericryptal granulomatous inflammation, and the presence of
      architectural alteration/activity/chronic inflammation/deep ulceration at sites
      that did not show granulomatous response in the same or adjacent segments.
      Although granulomas in CD were distributed throughout the colon, they were more
      frequent in the rectosigmoid than in TB. All biopsies from endoscopically
      abnormal sites did not show distinguishing features of TB or CD, emphasizing the
      need for multiple biopsies. There was an accrual in the number of diagnoses made
      with increasing numbers of biopsies from rectum to ileum. CONCLUSIONS: Histology
      of mucosal biopsies can aid in the differentiation of TB from CD, but multiple
      biopsies from different colonic segments are important for complete evaluation.

PMID- 15853981
TI  - Impaired capsaicin and neurokinin-evoked colonic motility in inflammatory bowel
      disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is associated with altered sensory
      and motor function in the human colon. The aim of the present study was to
      compare neuromuscular function in normal and IBD-affected colon in vitro, with
      emphasis on inhibitory enteric nerves, sensory neuropeptides and stimulation of
      axon collaterals. METHODS: Strips of longitudinal and circular muscle were
      prepared following colectomy from six patients with intestinal carcinoma (mean
      age 64.2 +/- 4.8 years) and six patients with IBD (Crohn's disease, n = 3;
      ulcerative colitis, n = 3: mean age 35.8 +/- 5.7 years). Responses were measured
      to electrical field stimulation, potassium chloride, 1,1-dimethyl-4
      phenylpiperazinium iodide, isoprenaline, calcitonin gene-related peptide (CGRP),
      capsaicin and neurokinin (NK)-1 and -2 receptor subtype-specific agonists, alone
      or after muscle precontraction. RESULTS: The NK-1 and CGRP receptor-mediated
      relaxation was reduced in the circular (by 44%, P < 0.05) and longitudinal (by
      61%, P < 0.05) muscle from IBD-affected colon, respectively. Maximal NK-2
      receptor-mediated contraction was also significantly decreased in both
      longitudinal (71%, P < 0.001) and circular (51%, P < 0.01) muscle. Capsaicin
      evoked relaxation in precontracted colonic longitudinal and circular muscle; this
      was significantly diminished in the IBD-affected colon (by 63%, P < 0.001 and
      76%, P < 0.01, respectively). Responses evoked by stimulation of enteric
      inhibitory nerves were not significantly altered. CONCLUSIONS: Colonic muscle
      strips from patients with IBD exhibited impaired CGRP and NK-1 receptor-mediated
      relaxation and NK-2 receptor-mediated contraction. Capsaicin-activated relaxation
      of colonic smooth muscle is deficient in IBD-affected colon. These results
      suggest a discrete effect of IBD on sensory-motor coupling and tachykinin
      mediated effects on colonic motility.

PMID- 15853982
TI  - Risk of colorectal cancer in ulcerative colitis in India.
AB  - BACKGROUND: The risk for colorectal cancer (CRC) in ulcerative colitis (UC) in
      India is not known. METHOD: Retrospective cohort from a tertiary level hospital
      in South India. Analysis of archived records of all patients with UC who
      underwent colonoscopy and segmental biopsies over the last 25 years. Incidence
      densities and risk of developing high grade dysplasia or CRC was calculated and
      chi-squared test was performed for risk factors of interest. RESULTS: Complete
      records were available for 532 patients, 336 (63.2%) male. The mean (+/- SEM)
      duration of illness was 6.04 +/- 0.29 years. In total, 234 patients (44%) had
      pancolitis, 121 (22.7%) had left-sided colitis and 177 (33.3%) had proctitis or
      proctosigmoiditis. Overall, five (0.94%) patients developed carcinoma and one
      (0.19%) patient had high grade dysplasia. The incidence density and risk of
      developing either CRC or high grade dysplasia was zero in the first 10 years of
      disease. In those with disease duration of 10-20 years, incidence density was
      2.34 per 1000 person years' duration (PYD) for all patients with colitis and 4.5
      per 1000 PYD for patients with pancolitis alone. This corresponded to risks of
      2.3% and 4.4%, respectively. For those with disease duration longer than 20
      years, incidence density was 2.73 per 1000 PYD for all patients and 4.9 per 1000
      PYD for patients with pancolitis. This corresponded to risks of 5.8% and 10.2%,
      respectively. Duration of disease beyond 10 years and extent of colitis were the
      only risk factors significantly associated with CRC. CONCLUSIONS: The risk of
      developing CRC is Indian patients with UC is lower than that reported from the
      West. Strategies for cancer surveillance in Indian patients with UC need to be
      tailored accordingly.

PMID- 15853983
TI  - Clinical significance of microsatellite instability in the inflamed mucosa for
      the prediction of colonic neoplasms in patients with ulcerative colitis.
AB  - BACKGROUND AND AIM: Although molecular mechanisms underlying ulcerative colitis
      (UC)-associated neoplasms have been studied for years, understanding of these
      mechanisms remains incomplete and no good predictable marker for development of
      colonic neoplasms in patients with UC has been established. The aim of this study
      was to assess if microsatellite instability (MSI) contributes to the development
      of colonic neoplasms in patients with UC. METHODS: We have examined MSI in
      chronic inflamed and neoplastic colonic mucosa of UC patients. We have also
      obtained serial biopsied colonic tissues retrospectively 2-12 years before the
      final diagnosis from patients with high level MSI (MSI-H+) UC-associated
      neoplasms, and analyzed MSI using them at different periods. RESULTS: Eight of 12
      UC-associated colon cancers (67%), four of six UC-associated high grade
      dysplasias (67%), and two of six UC-associated low grade dysplasias (33%)
      revealed MSI-H+ phenotypes. In contrast, 15 of 59 lesions (25%) in inflamed UC
      mucosa without colonic neoplasm revealed MSI-H +. Interestingly, all four
      patients with MSI-H+ phenotypes at the final diagnosis of UC-associated colon
      cancer or dysplasia had already had MSI-H+ at the stage of chronic colitis, 2-12
      years before the final diagnosis. CONCLUSION: These results support the notion
      that MSI contributes to the carcinogenesis of UC-associated neoplasms, and
      indicate that this analysis in inflamed colonic mucosa at surveillance
      colonoscopy is useful for identifying UC patients who have high risk for
      neoplastic progression.

PMID- 15853984
TI  - Push enteroscopy alters management in a majority of patients with obscure
      gastrointestinal bleeding.
AB  - INTRODUCTION: Although enteroscopy has been increasingly used to investigate
      occult or obscure bleeding, little is known about its impact on patient
      management. The aim of the present paper was to evaluate both the diagnostic
      yield and the impact of push enteroscopy on the management of patients referred
      to a tertiary Australian institution. METHODS: Data were collected prospectively
      in all patients undergoing push enteroscopy at Royal Adelaide Hospital. Fifty
      five patients were investigated for obscure gastrointestinal (GI) bleeding (25
      women, mean age 65.6 years), the cause of which remained unknown despite previous
      gastroscopy and colonoscopy. The patients were divided into two groups: occult
      obscure (anemia without macroscopic blood loss) and overt-obscure (macroscopic
      bleeding). Findings at enteroscopy, therapeutic procedures, and complications
      were recorded. Patients were followed to establish the impact of the procedure on
      subsequent management and clinical outcome. RESULTS: Enteroscopy demonstrated a
      potential site of bleeding in 38 patients (69%), and 38% of lesions found were
      within the reach of the gastroscope. The most common lesions were small
      intestinal angiodysplasia. Seventy-five percent of patients with positive
      findings had alterations to their management. After subsequent treatment, 62%
      were no longer anemic and there was a significant reduction in rebleeding (P <
      0.05) and transfusion requirements (P < 0.05) compared to patients with negative
      findings. The procedure was well tolerated and complications were rare.
      CONCLUSION: Enteroscopy has a positive impact on patient management and clinical
      outcome in a majority of patients with obscure gastrointestinal bleeding.

PMID- 15853985
TI  - Human immunodeficiency virus and endoscopy: Experience of a general hospital in
      Singapore.
AB  - INTRODUCTION: As the human immunodeficiency virus (HIV) pandemic continues,
      demand on the endoscopic services will also increase. The aim of the present
      study was to characterize the characteristics and endoscopic findings of HIV
      infected Asian patients. METHODS: Patients with HIV/AIDS who had endoscopy from
      January 1997 to September 2002 were identified and retrospectively reviewed.
      RESULTS: There were 125 patients (male, 111; mean age: 43.2 +/- 11 years; mean
      CD4 count 63 +/- 85/mm(3), range, 1-342/mm(3)) who underwent 181 procedures
      (upper gastrointestinal endoscopy [UGIE], n = 141; lower gastrointestinal
      endoscopy [LGIE], n = 40). The median time from diagnosis to endoscopy was 240
      days (-660 to 4680 days). For UGIE the main findings were candidiasis, 23.1%;
      cytomegalovirus esophagitis/ulcers, 11.2%; duodenal ulcers, 8.4%; gastric ulcers,
      7.0%; portal-hypertensive-related changes, 6.3%; idiopathic esophageal ulcers,
      3.5%; herpes simplex esophagitis/ulcers, 3.5%; and tuberculosis, 2.1%. The CD4
      counts were significantly lower in those with opportunistic infections (P =
      0.004) but there was no difference between significant and non-significant
      findings (P = 0.191). For LGIE 35% had endoscopic colitis, 80% of which were non
      specific. Significant findings were ileal tuberculosis, n = 3; colon cancer, n =
      1; and colonic fistula, n = 1. Ten patients had undergone 16 procedures (UGIE, n
      = 13; LGIE, n = 3) prior to the diagnosis of HIV/AIDS. They were all male Chinese
      patients, with positive contact with commercial sex workers (CSW) and had
      lymphopenia at time of endoscopy. The median time from endoscopy to diagnosis was
      180 days (range, 1-660 days). There were no significant differences in age (P =
      0.512) and CD4 count at diagnosis (P = 0.066) between patients who had endoscopy
      before and after diagnosis of HIV/AIDS. Four procedures led to the suspicion of
      HIV. CONCLUSIONS: Endoscopic findings of symptomatic HIV Asian patients are
      comparable to those of the West. Universal precautions should always be exercised
      in all procedures to avoid transmission of disease.

PMID- 15853986
TI  - Combination therapy with interferon-alpha and ribavirin in patients with dual
      hepatitis B and hepatitis C virus infection.
AB  - BACKGROUND: Patients with dual hepatitis B virus (HBV) and hepatitis C virus
      (HCV) infection have responded poorly to interferon (IFN) monotherapy. The
      purpose of the present paper was to assess the effect of combined IFN-alpha and
      ribavirin therapy in patients infected with both hepatitis B and C. METHODS:
      Thirty-six patients received 3 or 5 MU IFN-alpha-2b thrice weekly and oral
      ribavirin (800-1200 mg/day) for 24 weeks. All patients had positive hepatitis B
      surface antigen, antibody to HCV, and HCV-RNA. Before treatment, one patient had
      positive hepatitis B e antigen. Eighteen patients had positive HBV-DNA tested by
      Amplicor (Cobas Amplicor Monitor, Roche Diagnostics, Branchburg, NJ, USA), with a
      mean HBV-DNA level of 3.1 +/- 0.9 log copies/mL. Another 72 patients with HCV
      infection alone served as controls. RESULTS: Adverse events led to withdrawal in
      three patients receiving 5 MU IFN. Based on an intent-to-treat analysis, the
      biochemical response and serum HCV clearance rate at the end of 48 weeks follow
      up was similar in patients with dual infection and HCV infection alone (56% vs
      72%; and 69% vs 71%, respectively). There was no significant difference in
      sustained HCV clearance rate between the 3-MU group (n = 13) and the 5-MU group
      (n = 23; 85% vs 61%). At the end of 48 weeks follow up, two (11%) of 18
      pretreatment viremic patients had negative serum HBV-DNA (<200 copies/mL), while
      eight of those without pretreatment viremia had re-occurrence of HBV-DNA.
      CONCLUSIONS: Combination therapy with IFN-alpha and ribavirin was effective in
      achieving sustained HCV clearance in patients with dual HBV and HCV infection,
      comparable to those with hepatitis C infection alone. Combination therapy using 3
      MU IFN-alpha seemed as effective as 5 MU, and was well tolerated in the study
      population. However, large-scale control trials are necessary to clarify these
      findings.

PMID- 15853987
TI  - Human parvovirus B19 infection in patients with chronic hepatitis B or hepatitis
      C infection.
AB  - BACKGROUND AND AIM: Parvovirus B19 has been reported to be detected in the sera
      of patients with acute or chronic hepatitis. The prevalence and clinical
      significance of B19 DNA in serum samples from patients with chronic hepatitis B
      virus (HBV) and hepatitis C virus (HCV) infection were investigated. METHODS:
      Serum samples from 54 patients with HBV infection, 51 with HCV infection and 53
      normal controls were examined for anti-B19 antibodies and B19 DNA by enzyme
      linked immunosorbent assay (ELISA), the nested polymerase chain reaction (PCR),
      Southern blotting and direct nucleotide sequencing, respectively. RESULTS: Anti
      B19 IgM and IgG antibodies were detected in 19 (35.2%) and 46 (85.2%) of 54 serum
      samples from patients with HBV infection, and eight (15.7%) and 36 (70.6%) of 51
      serum samples from patients with HCV infection. B19 DNA was detected in serum
      samples of 20 (37%) of 54 patients with HBV infection and 12 (23.5%) of 51
      patients with HCV infection, but not in 53 serum samples from normal controls.
      The occurrence of liver dysfunction was not affected by B19 infection in patients
      with HBV and HCV infection (P > 0.05). All of the 20 serum samples with B19 DNA
      from patients with chronic HBV infection and all of the 12 serum samples with B19
      DNA from patients with chronic HCV infection exhibited TW-3 subtype and TW-9
      subtype, respectively. The variant subtypes of B19 were found to be distinctive
      in patients with HBV or HCV infection. CONCLUSIONS: These data revealed that
      human parvovirus B19 infection was frequently found in patients with chronic HBV
      or HCV infection. The variant genotypes were present in patients with different
      chronic hepatitis. The coinfection of B19 with HBV or HCV did not increase the
      frequency of liver dysfunction in patients with chronic hepatitis. Long-term
      longitudinal studies are required to determine the natural course of parvovirus
      B19 infection and whether its coinfection affects the natural history of chronic
      hepatitis B or hepatitis C.

PMID- 15853988
TI  - Liver histopathology in human immunodeficiency virus-hepatitis C virus co
      infected patients with fatal liver disease.
AB  - BACKGROUND: Liver failure is an increasing cause of death in human
      immunodeficiency virus-hepatitis C virus (HIV-HCV) co-infected patients. Here,
      histopathological features of fatal liver disease in HIV-HCV co-infected patients
      were comparatively assessed. METHODS: Liver biopsies of seven HIV-HCV co-infected
      patients with clinically imminent liver death and advanced immune deficiency were
      studied. Biopsies of seven asymptomatic patients with stable hepatic and immune
      functions, who were matched according to their documented duration of HIV-HCV co
      infection, served as controls. Inflammatory and fibrotic changes as well as
      hepatocellular steatosis and cholestasis were assessed semiquantitatively by
      established scores. RESULTS: All patients with fatal liver disease had severe
      immunodeficiency and jaundice, while biliary ducts were patent. Unexpectedly, the
      extent of hepatic steatosis, inflammatory activity and fibrosis was strikingly
      similar in both study groups. Importantly, liver failure was observed even in the
      absence of marked fibrosis. Lobular bilirubinostasis was the only feature that
      significantly distinguished patients with advanced immunodeficiency and fatal
      liver disease from the control group. CONCLUSION: Thus, rapid deterioration of
      liver function and death can occur in HIV-HCV co-infected patients with advanced
      immunodeficiency even when liver histology does not reveal markers of end-stage
      liver disease. Jaundice and marked bilirubinostasis in the absence of biliary
      tract obstruction seem to herald this complication of chronic hepatitis C in HIV
      infection.

PMID- 15853989
TI  - Clinical features of HBsAg-negative but anti-HBc-positive hepatocellular
      carcinoma in a hepatitis B virus endemic area.
AB  - BACKGROUND: The presence of antibody to the hepatitis B core antigen (anti-HBc)
      IgG in serum usually means a past infection of the hepatitis B virus (HBV). The
      clinical characteristics of patients with hepatocellular carcinoma (HCC), who
      have only a marker for past HBV infection, were investigated. METHODS: A total of
      565 HCC patients were classified according to their markers for HBV and the
      hepatitis C virus (HCV). The clinical features and the survival rate of hepatitis
      B surface antigen (HBsAg)(-)/anti-HBc(+) patients were compared to those of
      HBsAg(+) patients. RESULTS: Four hundred and three patients were positive for
      HBsAg (B group, 71.3%), 64 were positive for anti-HCV (11.3%), and 90 were
      negative for both HBsAg and anti-HCV (N group, 15.9%). In the N group, 71 were
      positive for anti-HBc (PB group, 12.6% of total patients). The clinical
      characteristics of the PB group were different from those of the B group: age at
      diagnosis (60.6 +/- 9.6 vs 53.3 +/- 10.6 years, P < 0.001), habitual drinking
      (59.2% vs 23.6%, P < 0.001), family history of liver disease (9.9% vs 38.9%, P <
      0.005), detection with periodic screening (28.2% vs 50.4%, P < 0.001), and
      elevated alpha-fetoprotein (53.5% vs 76.2%, P < 0.001). In both the PB group and
      the B group, liver cirrhosis was accompanied by a similar high prevalence (74.6%
      vs 89.1%). However, there was no significant difference in the cumulative
      survival rate. CONCLUSIONS: The prevalence of HBsAg(-)/anti-HBc(+) HCC is not
      rare or more common than that of anti-HCV(+) HCC in Korea, a high HBV endemic
      area. Although some differences in clinical characteristics may imply a different
      pathogenesis, chronic HBV infection or habitual drinking may be major
      contributing factors in the development of HCC in these patients.

PMID- 15853990
TI  - Risk factors for the development of hepatocellular carcinoma among patients with
      chronic hepatitis C who achieved a sustained virological response to interferon
      therapy.
AB  - BACKGROUND AND AIM: Hepatitis C virus (HCV)-infected patients who responded to
      interferon (IFN) treatment with clearance of serum HCV RNA may rarely develop
      hepatocellular carcinoma (HCC). The aim of the present study was to elucidate the
      risk factors for liver carcinogenesis among such patients. METHODS: In total, 126
      patients with chronic hepatitis C (CHC) who achieved a sustained virological
      response (SVR) to IFN monotherapy, which was defined as the absence of detectable
      HCV RNA in the serum at 6 months after completion of treatment, were enrolled and
      possible risk factors for HCC were analyzed. RESULTS: During the observation
      period of 66 +/- 36 months after cessation of IFN treatment, five (4.0%) of the
      126 patients developed HCC. The cumulative incidence of HCC at 3, 5 and 10 years
      was estimated to be 0.9, 4.7 and 7.5%, respectively. The cumulative incidence of
      HCC was significantly higher among patients with severe fibrosis (F3 or F4) than
      among patients with no or mild fibrosis (F0 to F2) in the liver before treatment
      (P = 0.007); among patients with alcohol intake of > or = 27 g/day than among
      patients with that of < 27 g/day (P = 0.015); and among patients who were > or =
      65 years old than among patients who were < 65 years old at the start of
      treatment (P = 0.026). CONCLUSIONS: Patients with CHC who had severe fibrosis,
      who had regularly taken moderate amounts of alcohol, or who were > or = 65 years
      at the start of IFN treatment should be carefully followed to detect small and
      controllable HCC, even after eradication of HCV.

PMID- 15853991
TI  - Clinicopathologic features of patients with primary malignant hepatic tumors
      seropositive for alpha-fetoprotein-L3 alone in comparison with other patients
      seropositive for alpha-fetoprotein-L3.
AB  - BACKGROUND: Patients with hepatocellular carcinoma (HCC) seropositive for lectin
      reactive alpha-fetoprotein (AFP-L3) have a poor prognosis. However, there have
      been no studies of the clinicopathologic features of patients seronegative for
      both AFP and des-gamma-carboxy prothrombin (DCP), and seropositive for AFP-L3
      alone in comparison with other patients seropositive for AFP-L3. METHODS:
      Patients with primary malignant hepatic tumors seropositive for AFP-L3 who
      underwent hepatectomy (n = 84) were divided into four groups, and their
      clinicopathologic features were compared: (i) group A, seronegative for AFP <100
      ng/mL and DCP <40 mAU/mL; (ii) group B, seropositive for AFP > or =100 ng/mL and
      seronegative for DCP; (iii) group C, seronegative for AFP and seropositive for
      DCP > or =40 mAU/mL; and (iv) group D, seropositive for AFP and DCP. RESULTS:
      Among the 14 group A patients seropositive for AFP-L3 alone with low AFP
      concentrations, three had intrahepatic cholangiocarcinoma (ICC), one had a
      cholangiolocellular carcinoma, one had combined HCC and ICC, and one had
      undifferentiated hepatic sarcoma. Group A had a higher incidence of non-HCC
      tumors (P < 0.001) and tumors derived from cholangiocytes (P < 0.001) than the
      other three groups. They also had a high frequency of poorly differentiated
      tumors and sarcomatous changes, and showed a poor prognosis. CONCLUSIONS:
      Patients with primary malignant hepatic tumors seropositive for AFP-L3 alone with
      low AFP concentrations have unique clinicopathologic features. Thus, we should be
      aware of these patients and should measure AFP-L3 levels, at least once, even in
      those seronegative for both AFP and DCP.

PMID- 15853992
TI  - Evaluation of predictive value of CLIP, Okuda, TNM and JIS staging systems for
      hepatocellular carcinoma patients undergoing surgery.
AB  - BACKGROUND: An accurate staging system is required to assess hepatocellular
      carcinoma (HCC) patients in order to benefit from hepatic resection before
      surgery. Cancer of the Liver Italian Program (CLIP) score was considered to be
      better than the Okuda staging system to predict survival. Japan Integrated
      Staging Score (JIS score) includes tumor, nodes, metastases (TNM) stage and Child
      Pugh grade as a new staging system for HCC. The purpose of the present paper was
      to compare the CLIP, Okuda, TNM and JIS staging systems for HCC patients
      undergoing surgery. METHODS: From 1991 to 1995, 599 patients undergoing hepatic
      resection for HCC from four medical centers in Taiwan were evaluated. All
      patients were classified by Okuda, CLIP, TNM and JIS systems. Factors associated
      survivals were analyzed. RESULTS: There was no statistical difference in survival
      between CLIP 0 and 1 patients, or among CLIP 2-4 patients. The prognostic
      validation of the Okuda and CLIP scoring systems in discriminating survival in
      HCC patients undergoing surgery was not satisfied. The TNM system was successful
      in predicting survival for HCC patients undergoing surgery. The JIS score could
      also differentiate survivals for those patients except for JIS 3. By multivariate
      analysis, age > or =60 years old, serum albumin <3.5 g/dL, tumor size >5 cm and
      TNM stage were associated with survival. CONCLUSION: Both the Okuda and CLIP
      systems are not superior to TNM staging for HCC patients who undergo surgical
      resection. Whether JIS score is feasible for those patients with advanced HCC
      needs further evaluation.

PMID- 15853993
TI  - Influence of juxtapapillary diverticulum on hepatic clearance in patients after
      endoscopic sphincterotomy.
AB  - BACKGROUND AND AIM: The role of juxtapapillary diverticulum ( JPD) in biliary
      stone formation is controversial. This study was designed to understand the
      relationship between the size of JPD, hepatic clearance and recurrent bile duct
      stones in patients after endoscopic sphincterotomy. METHODS: Five hundred and
      twenty patients with choledocholithiasis who had received endoscopic
      sphincterotomy were enrolled. They were divided into three groups: group A (n =
      268) without diverticula; group B (n = 156) with small diverticula; and group C
      (n = 96) with large diverticula. All patients were regularly followed with
      interviews, liver function test and sonogram to detect the recurrent bile duct
      stones. Quantitative cholescintigraphy was performed in 176 cholecystectomized
      patients to evaluate the hepatic clearance. Sphincter of Oddi manometry was
      performed to exclude incomplete sphincterotomy if quantitative cholescintigraphy
      was abnormal. RESULTS: After 9-111 months of follow-up, 76 patients had recurrent
      bile duct stones. There was a significant higher bile duct stone recurrence in
      group C than in group A (P < 0.01), but no statistical difference was noted
      between group B and group A (P = 0.2). Patients with JPD were older than those
      without (P < 0.05). Of 176 cholecystectomized patients, two were excluded because
      sphincter of Oddi basal pressure was more than 10 mmHg. In the remaining 174
      patients, the E45' was significantly lower in group C than in group A (41.2% +/-
      18.6%vs 49.1% +/- 14.1%; P < 0.05), and there was no significant difference
      between group B and group A. CONCLUSIONS: JPD is a predisposing factor of delayed
      biliary emptying and it increases the chance and incidence of recurrent bile duct
      stones.

PMID- 15853994
TI  - Symptomatic portal system thrombosis in soldiers due to extended stay at extreme
      altitude.
AB  - BACKGROUND: With induction of Indian Army to heights over 5000 m above mean
      sealevel (MSL), several new complications of long-term stay at extreme altitude
      have come to light. The authors' experience with soldiers who developed
      symptomatic portal system thrombosis (SPST) is described here. METHODS: Clinical
      data were prospectively collected between April 1998 and April 2003, on all
      patients hospitalized for SPST from high-altitude areas (HAA, >3000 m above MSL)
      and those from non-high-altitude areas (NHAA). Site of thrombosis was confirmed
      by imaging and included splenic, portal, superior mesenteric, or inferior
      mesenteric vein thrombosis. Patients were investigated to rule out known
      predisposing factors and prothrombotic conditions. RESULTS: A total of 37 cases
      of SPST were seen during the study period, of which 26 were from HAA. Mean age of
      cases from HAA was 27 +/- 4.6 years and all were male. Mean stay at high altitude
      was 11.7 +/- 6.2 months. First symptom was pain in abdomen in almost all the
      cases, later followed by gastrointestinal bleeding and fever in 14 each, and
      vomiting in 19. Clinical examination showed ascites (81%), splenomegaly (76.9%),
      and hepatomegaly (69.2%). Diagnosis was made by imaging scans (23 cases) and on
      surgery in three cases. A known prothrombotic state was detected in five cases
      from HAA and in eight cases from NHAA (P < or = 0.01). Ultrasound Doppler scan
      picked up collaterals as early as 12-45 days after onset of symptoms.
      CONCLUSIONS: Extended stay at HAA may be a risk factor for development of
      symptomatic portal system thrombosis.

PMID- 15853995
TI  - Biliary excretion of olmesartan, an anigotensin II receptor antagonist, in the
      rat.
AB  - BACKGROUND AND AIM: Olmesartan (RNH-6270) is a newly developed anigotensin II
      receptor antagonist, and has been reported to be excreted into feces. To examine
      the mechanism of the biliary excretion of olmesartan, we studied its biliary
      excretion in rats. METHODS: The biliary excretion of olmesartan in Eisai
      hyperbilirubinemic rats (EHBR), a multidrug resistance protein 2-deficient rat,
      was compared with control rats, and the effect of organic anions and cation and
      bile acids on the biliary excretion of olmesartan was studied in control rats.
      RESULTS: The biliary excretion of olmesartan was markedly delayed in EHBR. The
      biliary excretion of olmesartan was inhibited by sulfobromophthalein, cefpiramide
      and pravastatin, but was not inhibited by taurocholate or tauroursodeoxycholate.
      Vinblastine inhibited and phenothiazine treatment increased the biliary excretion
      of olmesartan. CONCLUSIONS: These findings suggest that olmesartan is excreted
      into the bile mainly by multidrug resistance protein 2 and partly by P
      glycoprotein.

PMID- 15853996
TI  - Images of interest. Gastrointestinal: bleeding from ischemic colitis.

PMID- 15853997
TI  - Images of interest. Gastrointestinal: sigmoid volvulus.

PMID- 15853998
TI  - Images of interest. Hepatobiliary and pancreatic: biliary cast syndrome.

PMID- 15853999
TI  - Images of interest. Hepatobiliary and pancreatic: hepatic granulomas and
      hepatitis C.

PMID- 15854000
TI  - Polymorphism and gastric cancer.

PMID- 15854001
TI  - Multiple hypervascular liver nodules in a heavy drinker of alcohol.
AB  - A case of hypervascular nodules in the liver, but without hepatitis B or C virus
      infection in a 38-year-old woman with a history of alcohol abuse is presented. An
      ultrasound disclosed 1-2-cm hypoechoic tumors in the right and left lobes.
      Magnetic resonance imaging showed high-intensity tumors at both the T1-weighted
      and T2-weighted sequences. Incremental dynamic computed tomography and hepatic
      angiography revealed hypervascular tumors. Ultrasound-guided needle biopsy
      revealed no evidence of hepatocellular carcinoma, metastatic liver cancer,
      hemangioendothelioma, inflammatory pseudotumors or pseudolymphoma, but
      demonstrated stellate-scar fibrosis septa, which contained small unpaired
      arteries without hyperplasia dividing the nodule. Moreover, marked pericellular
      fibrosis, neutrophilic infiltration and Mallory bodies were observed in the
      cytoplasm. There was no evidence of bile duct proliferation. From these findings,
      the diagnosis of alcohol-induced fibrosis, distinctly different from focal
      nodular hyperplasia, was tenable. Further studies may provide insights into the
      pathogenesis of nodule formation and hypervascularity in heavy drinkers of
      alcohol.

PMID- 15854002
TI  - Pseudomalignant erosion in hyperplastic polyp at esophago-gastric junction.

PMID- 15854003
TI  - Polymyalgia rheumatica presenting as acute cholestatic hepatitis.

PMID- 15854004
TI  - Retroperitoneal bronchogenic cyst mimicking pancreatic pseudocyst in a patient
      with colorectal cancer.

PMID- 15854006
TI  - Things I've learned about personality from studying political leaders at a
      distance.
AB  - Studying the personalities of political leaders requires methods of measuring
      personality at a distance. One such method is content analysis of speeches,
      interviews, and other texts. This article reviews the author's research on
      achievement, affiliation, and power motives of U.S. presidents and other leaders
      and draws the following conclusions: (1) motivation and personality can be
      objectively and reliably measured at a distance; (2) personality is complex,
      consisting of several different elements or kinds of variables (e.g., motives and
      cognitions as well as traits); (3) personality exists in social contexts, and
      past social contexts are embodied in personality; (4) political behaviors and
      outcomes can be predicted from personality, but only in contingent ("if/then")
      ways.

PMID- 15854007
TI  - Linking personality to helping behaviors at work: an interactional perspective.
AB  - Previous efforts to elucidate dispositional antecedents of organizational
      citizenship behaviors have yielded equivocal results. The current study presents
      and tests a theoretical argument for expecting conscientiousness to interact with
      interpersonal dimensions of personality in predicting helping behaviors. As
      hypothesized, the responses of 374 women and their supervisors reveal significant
      interactions between conscientiousness, on the one hand, and agreeableness,
      extraversion, and emotional stability, on the other, in predicting helping
      behaviors. Clarifying the relationship between personality and helping, these
      results suggest that the impact of conscientiousness in a social context depends
      on a positive interpersonal orientation. The implications of these findings for
      research and practice are discussed.

PMID- 15854008
TI  - Cognitive coping with the threat of rape: vigilance and cognitive avoidance.
AB  - Individual differences in women's avoidant and vigilant style in coping with the
      threat of rape were explored in four studies. In the first study, 97 women read a
      rape scenario and completed measures of cognitive vigilance and avoidance. They
      also provided ratings of fear of rape and anticipated coping problems in case of
      sexual assault. Vigilance was associated with significantly higher levels of fear
      of rape and anticipation of more severe coping problems. No effects were found
      for cognitive avoidance. Study 2 replicated these findings with a sample of 275
      women. In addition, it showed that high vigilance was associated with
      significantly more rape-preventive behaviors. Study 3, including 172 women, was
      an online study on the effect of cognitive coping style on fear of rape,
      anticipated coping problems, and two behavioral measures of rape avoidance. High
      vigilance was related to higher levels of fear of rape, anticipation of more
      severe coping problems, and more rape-preventive behaviors. Finally, Study 4
      (N=210) showed that individual differences in cognitive coping style affected
      rape-related affect and behavior in the absence of a rape scenario, underlining
      the chronic salience of the threat of rape for women. Vigilance was positively
      related to fear of rape, rape-avoidance behavior, and anticipated coping
      problems. In contrast, a negative relationship was found between cognitive
      avoidance and fear of rape, rape-avoidance strategies, and anticipated coping
      problems. Across the four studies, no evidence was found for an interactive
      effect of cognitive avoidance and vigilance, as suggested by the construct of
      repression versus sensitization. The findings are discussed in the light of
      previous research on repression-sensitization in coping with threatening
      information.

PMID- 15854009
TI  - Processes underlying gender-role flexibility: do androgynous individuals know
      more or know how to cope?
AB  - This research examined gender-role flexibility across a variety of stressful
      events, and tested two proposed hypotheses that explicate the processes
      underlying gender-role flexibility. The knowing-more hypothesis posits that
      androgynous individuals have a broad coping repertoire. The knowing-how
      hypothesis posits that androgynous individuals know how to cope according to
      changing situational characteristics. The coping responses of Chinese university
      students were assessed in both real-life (Study 1) and hypothetical (Study 2)
      stressful situations. Results revealed that androgynous participants, who were
      less depressed than others, were characterized by (a) cognitive astuteness in
      distinguishing among situational characteristics and (b) deployment of strategies
      that fit specific situational demands. Results supported the knowing-how
      hypothesis only.

PMID- 15854010
TI  - Interpersonal perception and pathological personality features: consistency
      across peer groups.
AB  - This study investigated the consistency of interpersonal perceptions regarding
      people who exhibit features of personality disorders. The participants (N=82)
      were college students who were assessed for features of personality disorders,
      using both self-report and peer nominations at Time 1. Two years later,
      participants attended four meetings in groups of 7 to 12 people for a total of 2
      hours. Group discussions were designed to encourage interaction and give
      participants an opportunity to behave in ways that might be expected from people
      with personality problems. After Meetings 1 and 4, group members ranked their
      impressions of each other with regard to several personality traits and
      behavioral attributes. We observed important consistencies between the peer
      nominations collected at Time 1 and personality rankings made by a different peer
      group at Time 2. There was considerable convergence between personality disorder
      features and negative evaluations by others, with participants high in detachment
      eliciting the most negative reactions from peers in the lab.

PMID- 15854011
TI  - Subdomains of gender-related occupational interests: do they form a cohesive
      bipolar M-F dimension?
AB  - In four studies, with a total of 1780 male and 2969 female participants,
      subdomains of masculine and feminine occupations were identified from sets of
      occupational preference items. Identified masculine subdomains included "blue
      collar realistic" (e.g., carpenter), "educated realistic" (electrical engineer),
      and "flashy, risk-taking" (jet pilot). Feminine subdomains included "fashion
      related" (fashion model), "artistic" (author), "helping" (social worker), and
      "children-related" (manager of childcare center). In all studies, principal
      components analyses of subdomain preference scales showed that masculine
      subdomains were bipolar opposites of feminine subdomains. This bipolar structure
      emerged in analyses conducted on combined-sex groups, high-school boys, high
      school girls, men, women, heterosexual men, gay men, heterosexual women, and
      lesbian women. The results suggest that, although there are distinct masculine
      and feminine occupational subdomains, gender-related occupational preferences,
      nonetheless, form a replicable, cohesive, bipolar individual difference
      dimension, which is not an artifact of studying mixed-sex or mixed-sexual
      orientation groups.

PMID- 15854012
TI  - Contrasting effects of self-schema priming on lexical decisions and interpersonal
      stroop task performance: evidence for a cognitive/interactionist model of
      interpersonal dependency.
AB  - Four experiments tested a key tenet of Bornstein's (1992, 1993)
      cognitive/interactionist (C/I) model of interpersonal dependency: that priming
      the helpless self-schema (HSS) alters processing of dependency-related
      information in dependent--but not nondependent--individuals. Experiments 1 and 2
      assessed the effects of subliminal lexical priming and an emotional priming
      manipulation on lexical decision (LD) judgments for dependency-related words and
      control words. Experiments 3 and 4 assessed the effects of these same priming
      procedures on Interpersonal Stroop Task (IST) performance. As predicted, priming
      the HSS produced contrasting effects on different outcome measures, decreasing LD
      latencies, but increasing IST response times. Results are discussed in the
      context of the C/I model, and suggestions for future studies are offered.

PMID- 15854013
TI  - Prayers, spiritual support, and positive attitudes in coping with the September
      11 national crisis.
AB  - This study was designed to help fill gaps in faith-related and positive
      psychology research. Psychologists have called for precise assessment of
      effective faith factors inherent within spiritual experiences that may explain
      their beneficial effects. Positive psychologists suggest the need to examine
      social and faith-related origins of optimism. Based on previous research, we
      redefined spiritual support and developed a new assessment. The study is a survey
      of 453 graduate and undergraduate students 3 months after the September 11, 2001,
      terrorist attacks. The results showed that participants, who believed in diverse
      spiritual entities, used various types of prayer for coping. A structural
      equation model showed that a linkage of spiritual support and positive attitudes
      mediated the effect of faith-based and secular factors on post-September 11
      distress. Higher levels of initial negative emotional response were associated
      with the use of prayer for coping, which was, in turn, related to less distress
      through the pathway of the above linkage.

PMID- 15854014
TI  - Continuity and correlates of emotions and motives in self-defining memories.
AB  - Two studies examined emotions and motives in self-defining memories. In Study 1,
      participants recalled five self-defining memories (four recent and one earliest
      childhood), rated their emotions and motives during each memory, and completed a
      set of personality measures. A subset of participants provided a second set of
      memories, as well as emotion and motive ratings, approximately 2 weeks after the
      initial session. Results suggest that emotions and motives are moderately stable
      across memories and over time and show theoretically meaningful relations with
      self-esteem, narcissism, and affective dispositions. Study 2 extended the
      findings of Study 1 to a longitudinal context. Emotions and motives coded from
      self-defining memories were associated with changes in personality, well-being,
      and academic performance over a 4-year period.

PMID- 15854019
TI  - Implications of Epstein-Barr Virus (EBV)-induced carcinogenesis on cutaneous
      inflammation and carcinogenesis: evidence of recurring patterns of angiogenesis
      and signal transduction.

PMID- 15854020
TI  - Our legacy-of what? Of the JID, of dermatology, of physician-hood, of (wo)man
      hood?

PMID- 15854021
TI  - Osteopontin in melanocytic lesions--a first step towards invasion?

PMID- 15854022
TI  - Clothing the nude: a new model for trichogenesis.

PMID- 15854023
TI  - Osteopontin expression correlates with melanoma invasion.

PMID- 15854024
TI  - Organogenesis from dissociated cells: generation of mature cycling hair follicles
      from skin-derived cells.
AB  - Hair follicle formation and cycling involve extensive and continuous interactions
      between epithelial and mesenchymal components. A system for rapidly and
      reproducibly generating hair follicles from dissociated epithelial and
      mesenchymal cells is described here. The system serves both as a tool for
      measuring the trichogenic property of cells and as a tool for studying the
      mechanisms that dissociated cells use to assemble an organ. In this system, hair
      follicles develop when dissociated cells, isolated from newborn mouse skin, are
      injected into adult mouse truncal skin. This morphogenetic process involves the
      aggregation of epithelial cells to form clusters that are sculpted by apoptosis
      to generate "infundibular cysts". From the "infundibular cysts", hair germs form
      centrifugally followed by follicular buds and then pegs that grow asymmetrically
      to differentiate into cycling mature pilosebaceous structures. Marker studies
      correlate the molecular differentiation of these follicles with in situ systems.
      This study suggests that the earliest phase of a developing epithelial
      mesenchymal system--even from dissociated cell preparations--requires an
      epithelial platform.

PMID- 15854025
TI  - Comprehensive analysis of FGF and FGFR expression in skin: FGF18 is highly
      expressed in hair follicles and capable of inducing anagen from telogen stage
      hair follicles.
AB  - We quantified the mRNA expression of all 22 fibroblast growth factor family
      members (FGF) and their four receptors (FGFR) in adult mouse full-thickness skin
      at various stages of the hair growth cycle. We found that in addition to mRNA
      encoding FGF previously identified in skin (FGF1, 2, 5, 7, 10, 13, and 22), FGF18
      mRNA was also strongly expressed. Expression of these FGF varied throughout hair
      growth cycle: mRNA expression of FGF18 and 13 peaked at telogen; FGF7 and 10 at
      anagen V; and FGF5 and 22 at anagen VI. In situ hybridization revealed that FGF18
      mRNA is mainly expressed in the anagen inner root sheath and telogen bulge of
      hair follicles. In culture, FGF18 stimulated DNA synthesis in human dermal
      fibroblasts, dermal papilla cells, epidermal keratinocytes and vascular
      endothelial cells. When FGF18 was administered subcutaneously to mice in a
      uniform telogen state, anagen hair growth was observed. Our findings suggest that
      FGF18 is important for the regulation of hair growth and the maintenance of skin
      in adult mice.

PMID- 15854026
TI  - Constitutive phosphorylation of focal adhesion kinase is involved in the
      myofibroblast differentiation of scleroderma fibroblasts.
AB  - Most of the cultured scleroderma fibroblasts have been reported to be
      myofibroblasts that have the ability to express alpha smooth muscle actin
      (alphaSMA). It is reported that, in human lung fibroblasts, alphaSMA is induced
      by transforming growth factor-beta (TGF-beta), which requires focal adhesion
      kinase (FAK) phosphorylation on its Tyr-397 site. In this study, we investigated
      how alphaSMA expression is upregulated in cultured scleroderma fibroblasts. 4
      amino-5-(4-chlorophenyl)-7-(butyl)pyrazolo[3,4-d]pyrimidine, which is a
      pharmacologic inhibitor of FAK/Src, markedly diminished upregulated alphaSMA
      expression in scleroderma fibroblasts as well as in normal fibroblasts stimulated
      with TGF-beta. Likewise, alphaSMA expression was significantly reduced in
      sclerderma fibroblasts transfected with kinase-deficient FAK mutant. FAK
      phosphorylation levels on Tyr-397 in scleroderma fibroblasts were significantly
      higher than those in normal fibroblasts. Both alphaSMA expression and FAK
      phosphorylation levels in scleroderma fibroblasts were markedly diminished by the
      treatment with TGF-beta antisense oligonucleotide. These results indicate that
      the constitutive phosphorylation of FAK, which is possibly because of the
      autocrine TGF-beta signaling, may play an important role in alphaSMA expression
      in scleroderma fibroblasts.

PMID- 15854027
TI  - Fifteen-year follow-up of hand eczema: predictive factors.
AB  - The aim of this study was to identify factors of importance for the long-term
      prognosis of hand eczema in the general population. In a 15-y follow-up, 868
      (78%) individuals with hand eczema, diagnosed and clinically examined in a
      previous population-based study, answered a postal questionnaire with questions
      concerning persistence of the disease. In a logistic regression model, the extent
      of eczema involvement at the initial examination was the strongest negative
      factor for the prognosis, followed by history of childhood eczema and age below
      20 y at onset of hand eczema. These factors significantly influenced both the
      total time with hand eczema during the 15 y follow-up and occurrence of hand
      eczema the previous year. The predictive factor for hand eczema 15 y later was
      doubled for an individual with all three risk factors compared with one without
      them, 72%vs 35%. Contact allergy to any of the standard allergens also related
      significantly to current hand eczema. In conclusion, the main determinant for a
      poor long-term prognosis was widespread hand dermatitis at the initial
      examination. Other important factors were low age at onset of hand eczema,
      history of childhood eczema, and contact allergy.

PMID- 15854028
TI  - Hyaluronan synthase induction and hyaluronan accumulation in mouse epidermis
      following skin injury.
AB  - Hyaluronan, a major extracellular matrix component in the epidermis, has been
      shown to control keratinocyte proliferation and differentiation in vitro. We
      assayed hyaluronan and hyaluronan synthases (has1-3) in mouse epidermis during
      fetal development, postnatal life, and trauma reaction in vivo. Hyaluronan
      increased in the epidermis when keratinocytes started to stratify on day E15,
      remained high until birth, and then rapidly declined, with corresponding changes
      in the mRNA levels of has2 and has3. The hyaluronan in adult mouse epidermis
      mainly resided around the orifices of the hair follicles, and the overall
      concentration was about one order of magnitude lower than in adult human
      epidermis. In adult mice, epidermal trauma caused by tape stripping rapidly
      increased hyaluronan, leading to a 6-fold increase in epidermal hyaluronan on day
      3 following trauma. The hyaluronan response was associated with a strong
      induction of has2 and has3 mRNA, slightly higher CD44 expression, and
      considerable epidermal hyperplasia. The data show that the pre- and postnatal
      fluctuations in epidermal hyaluronan content correlate with the expression levels
      of has2 and has3. Stimulated hyaluronan synthesis through upregulated has
      expression is an inherent feature of the keratinocyte activation triggered by
      tissue trauma, and presumably important for a proper healing response.

PMID- 15854029
TI  - Three-dimensional migration of human adult dermal fibroblasts from collagen
      lattices into fibrin/fibronectin gels requires syndecan-4 proteoglycan.
AB  - Fibroblast migration from the peri-wound collagenous stroma into the fibrin-laden
      wound is critical for granulation tissue formation and subsequent healing.
      Previously we found that fibroblast transmigration from a collagen matrix into a
      fibrin matrix required fibronectin (FN). Integrins alpha4beta1, alpha5beta1, and
      alphavbeta3 and dermatan sulfate CD44 were required for this invasive migration.
      Here we demonstrated that syndecan-4, a transmembrane heparan sulfate (HS)
      proteoglycan, known to bind FN, is also required for fibroblast invasive
      migration of a fibrin/FN gel. This conclusion was based on fibroblast migration
      using two independent means of disrupting syndecan-4: heparinase degradation of
      HS glycosaminoglycans or suppression of syndecan-4 core protein with antisense
      oligodeoxynucleotides. Isolated syndecan-4 from these fibroblasts bound Hep II
      recombinant constructs FN III12-V15>FN III12-15>FN III12-14 but did not bind the
      IIICS (V) domain. Furthermore, platelet-derived growth factor (PDGF), which is
      required to stimulate fibroblast migration, markedly increased cell levels of
      syndecan-4 core protein in a time and concentration-dependent fashion. PDGF also
      induced upregulation of syndecan-4 at transcriptional level as determined by RT
      PCR. These results demonstrate that syndecan-4 is essential for fibroblast
      invasive migration into fibrin clot and that PDGF, the stimulus for migration,
      induces increased syndecan-4 core protein expression.

PMID- 15854030
TI  - A novel mutation in the lysyl hydroxylase 1 gene causes decreased lysyl
      hydroxylase activity in an Ehlers-Danlos VIA patient.
AB  - The clinical diagnosis of a patient with the phenotype of Ehlers-Danlos syndrome
      type VI was confirmed biochemically by the severely diminished level of lysyl
      hydroxylase (LH) activity in the patient's skin fibroblasts. A novel homozygous
      mutation, a single base change of T(1360)-->G in exon 13 of the LH1 gene,
      predicted to result in W446G, was identified in the patient's full-length cDNA.
      This was confirmed in genomic DNA from both the patient and her parents, who were
      heterozygous for the mutation. This mutation was introduced into an LH1-pAcGP67
      baculoviral construct and expressed, in parallel with normal LH1, in an insect
      cell system. The loss of LH activity in the mutated recombinant construct
      confirmed the pathogenicity of this mutation. Although not in the major catalytic
      site, this mutation occurs in a highly conserved region of the LH1 gene and may
      contribute to loss of activity by interfering with normal folding of the enzyme.

PMID- 15854031
TI  - Mutations in the CYLD gene in Brooke-Spiegler syndrome, familial cylindromatosis,
      and multiple familial trichoepithelioma: lack of genotype-phenotype correlation.
AB  - Brooke-Spiegler syndrome (BSS), familial cylindromatosis (FC), and multiple
      familial trichoepithelioma (MFT), originally described as distinct entities,
      share overlapping clinical findings. Patients with BSS are predisposed to
      multiple skin appendage tumors such as cylindroma, trichoepithelioma, and
      spiradenoma. FC, however, is characterized by cylindromas and MFT by
      trichoepitheliomas as the only tumor type. These disorders have recently been
      associated with mutations in the CYLD gene. In this report, we describe three
      families with BSS, one with FC, and two with MFT phenotypes associated with novel
      and recurrent mutations in CYLD. We provide evidence that these disorders
      represent phenotypic variation of a single entity and lack genotype-phenotype
      correlation.

PMID- 15854032
TI  - Fine mapping of the psoriasis susceptibility gene PSORS1: a reassessment of risk
      associated with a putative risk haplotype lacking HLA-Cw6.
AB  - Human leukocyte antigen (HLA)-Cw6 has long been associated with psoriasis, and
      PSORS1 (psoriasis susceptibility 1), a major gene for psoriasis susceptibility,
      has been mapped to its vicinity. A previous analysis identified multiple risk
      haplotypes carrying HLA-Cw6 and one haplotype (cluster 17, HLA-Cw8-B65) that
      appeared to carry risk for psoriasis but did not carry HLA-Cw6. This haplotype
      was very similar to other risk haplotypes for at least 60 kb telomeric to HLA-C,
      suggesting identity by descent with the remaining risk chromosomes. The
      association, however, between psoriasis and this haplotype as assessed by the
      transmission/disequilibrium test (TDT) was of borderline significance (p-value
      0.048). In order to better assess the risk associated with cluster 17, a
      multicenter collaboration typed additional subjects for a single marker (M6S161)
      for which one allele (249 bp) was found only on cluster 17. The new sample
      included 1275 pedigrees as well as 300 cases and 913 controls. Transmission of
      this allele to affected individuals was examined using the TDT and the pedigree
      disequilibrium test (PDT), and case-control samples were analyzed by a trend test
      across genotype categories. By all methods, the newly acquired genotypes failed
      to confirm the association originally reported, despite adequate power. In
      contrast, the 248 bp allele, which is found on all HLA-Cw6-positive risk
      haplotypes as well as several non-risk haplotypes, shows significant excess
      transmission for all cohorts. Taken together, these results indicate that cluster
      17 does not carry a psoriasis-susceptibility allele, and expand the PSORS1 risk
      interval to approximately 300 kb.

PMID- 15854033
TI  - Distinct strains of Propionibacterium acnes induce selective human beta-defensin
      2 and interleukin-8 expression in human keratinocytes through toll-like
      receptors.
AB  - Acne is a chronic inflammatory disease of the pilosebaceous follicle. One of the
      main pathogenetic factors in acne is the increased proliferation of
      Propionibacterium acnes (P. acnes) in the pilosebaceous unit. We investigated
      whether direct interaction of P. acnes with keratinocytes might be involved in
      the inflammation and ductal hypercornification in acne. The capacities of
      different P. acnes strains to activate the innate immune response and the growth
      of cultured keratinocytes were investigated. We have found that two clinical
      isolates of P. acnes significantly induced human beta-defensin-2 (hBD2) messenger
      RNA (mRNA) expression; in contrast a third clinical isolate and the reference
      strain (ATCC11828) had no effect on hBD2 mRNA expression. In contrast, all four
      strains significantly induced the interleukin-8 (IL-8) mRNA expression. The P.
      acnes-induced increase in hBD2 and IL-8 gene expression could be inhibited by
      anti-Toll-like receptor 2 (TLR2) and anti-TLR4 neutralizing antibodies,
      suggesting that P. acnes-induced secretion of soluble factors in keratinocytes
      are both TLR2 and TLR4 dependent. In addition, the clinical isolate P. acnes
      (889) was capable of inducing keratinocyte cell growth in vitro. Our findings
      suggest that P. acnes modulates the antimicrobial peptide and chemokine
      expression of keratinocytes and thereby contributes to the recruitment of
      inflammatory cells to the sites of infections.

PMID- 15854034
TI  - In vitro keratinocyte dissociation assay for evaluation of the pathogenicity of
      anti-desmoglein 3 IgG autoantibodies in pemphigus vulgaris.
AB  - Patients with pemphigus vulgaris (PV) have circulating anti-desmoglein (Dsg) 3
      immunoglobulin G (IgG) autoantibodies that induce blister formation. We developed
      an in vitro quantitative assay to evaluate the pathogenic strength of anti-Dsg3
      IgG autoantibodies in blister formation. To obtain intercellular adhesion
      mediated dominantly by Dsg3, we used primary cultured normal human keratinocytes
      expressing low level of Dsg2 in the presence of exfoliative toxin A that
      specifically digests Dsg1. After incubation with various antibodies, monolayers
      released by dispase were subjected to mechanical stress by pipetting, and the
      number of cell fragments were counted. When anti-Dsg3 monoclonal antibodies (mAb)
      obtained from pemphigus model mice were tested, pathogenic AK23 mAb yielded
      significantly higher number of cell fragments than AK7 or AK20 non-pathogenic
      mAb. Dissociation scores, defined with AK23 mAb as the positive control, were
      significantly higher with active stage PV sera (n=10, 77.4+/-21.4) than controls
      (n=11, 16.0+/-9.6; p=0.003). When pair sera obtained from 6 PV patients in active
      stage and in remission were compared, the dissociation scores reflected well the
      disease activity as those in active stage were four to 17 times higher than those
      in remission. When sera from different patients showing similar ELISA scores but
      different clinical severity were tested (n=6), the dissociation scores with sera
      from severe disease activity were significantly higher than those with sera in
      remission. These findings indicate that this dissociation assay will provide a
      simple and objective biological method to measure the pathogenic strength of
      pemphigus autoantibodies.

PMID- 15854035
TI  - Transfer of CD8(+) cells induces localized hair loss whereas CD4(+)/CD25(-) cells
      promote systemic alopecia areata and CD4(+)/CD25(+) cells blockade disease onset
      in the C3H/HeJ mouse model.
AB  - Alopecia areata (AA) is a suspected hair follicle specific autoimmune disease.
      The potential for cell transfer of AA using the C3H/HeJ mouse model was examined.
      Cells isolated from lymph nodes and spleens of AA-affected mice using magnetic
      bead conjugated monoclonal antibodies were subcutaneously injected into normal
      C3H/HeJ recipients. Within 5 wk, all CD8(+) cell-injected mice exhibited
      localized hair loss exclusively at the site of injection that persisted until
      necropsy. In contrast, some CD4(+) and CD4(+)/CD25(-) cell-injected mice
      developed extensive, systemic AA, and a combination of CD8(+) and CD4(+)/CD25(-)
      cells injected yielded the highest frequency of systemic AA induction.
      CD4(+)/CD25(+) cells were less able to transfer the disease phenotype, partially
      blockaded systemic AA induction by CD4(+)/CD25(-) cells, and prevented CD8(+)
      cell-induced, injection site-localized hair loss. CD11c(+) and CD19(+) cells
      failed to promote significant phenotype changes. Increases in co-stimulatory
      ligands CD40 and CD80, plus increased leukocyte apoptosis resistance with reduced
      CD95, CD95L, and CD120b expression, were associated with successful alopecia
      induction. The results suggest that CD8(+) cells may be the primary instigators
      of the hair loss phenotype. However, systemic disease expression fate is,
      apparently determined by CD4(+)/CD25(-) cells, while CD4(+)/CD25(+) lymphocytes
      may play a predominantly regulatory role.

PMID- 15854036
TI  - Evidence that anti-type VII collagen antibodies are pathogenic and responsible
      for the clinical, histological, and immunological features of epidermolysis
      bullosa acquisita.
AB  - Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease
      characterized by autoantibodies to type VII (anchoring fibril) collagen.
      Therefore, it is a prototypic autoimmune disease defined by a well-known
      autoantigen and autoantibody. In this study, we injected hairless immune
      competent mice with purified immunoglobulin G (IgG) fraction of serum from
      rabbits immunized with the non-collagenous amino-terminal domain (NC1) of human
      type VII collagen, the domain known to contain immunodominant epitopes. As a
      control, identical mice were injected with the IgG fraction of serum from non
      immunized rabbits. Mice injected with immune IgG developed subepidermal skin
      blisters and erosions, IgG deposits at the epidermal-dermal junction of their
      skin, and circulating anti-NC1 antibodies in their serum-all features reminiscent
      of patients with EBA. Similar concentrations of control IgG purified from normal
      rabbits did not induce disease in the mice. These findings strongly suggest that
      autoantibodies that recognize human type VII collagen in EBA are pathogenic. This
      murine model, with features similar to the clinical, histological, and
      immunological features of EBA, will be useful for the fine dissection of
      immunopathogenic mechanisms in EBA and for the development of new therapeutic
      interventions.

PMID- 15854037
TI  - Immunolocalization of low-affinity prostaglandin E receptors, EP and EP, in adult
      human epidermis.
AB  - Four prostaglandin (PG)E(2) receptors have been described, termed E-series
      prostaglandin receptors (EP(1)-EP(4)), that can be further subclassified as low
      affinity (EP(1) and EP(2)) or high-affinity (EP(3) and EP(4)) receptors.
      Activation of the low-affinity PGE(2) receptors is likely to be important in
      mediating the actions of the high levels of PGE(2) found in various pathologic
      processes. The pattern of expression of these receptors in epidermis, however, is
      unknown. We therefore examined the immunolocalization of the EP(1) and EP(2)
      receptors in human epidermis. The EP(1) and EP(2) receptors demonstrated both
      plasma membrane and perinuclear or nuclear staining within the basal and spinous
      layers. Within the granular layer, both receptors were expressed in the cytoplasm
      with a grainy or granular appearance. The major differences were that the EP(2)
      receptor demonstrated a zone of decreased to absent plasma membrane staining in
      the superficial spinous layer and only scattered cellular staining within the
      granular layer. In contrast, the EP(1) receptor was prominently expressed
      throughout the stratum granulosum and the plasma membrane staining pattern was
      seen throughout the spinous layer. In cultured primary human keratinocytes, we
      also verified the presence of functional EP(1) receptor coupled to intracellular
      calcium mobilization and EP(2) receptor coupled to cAMP production.

PMID- 15854038
TI  - Dermal delivery of topically applied oligonucleotides via follicular transport in
      mouse skin.
AB  - Antisense oligodeoxynucleotides formulated in cream preparations are being
      examined in the clinic as topical therapy for psoriasis. To produce their
      intended anti-inflammatory effects, these large anionic molecules must penetrate
      the stratum corneum and reach the living epidermis and dermis. A topically
      applied phosphorothioate antisense oligonucleotide targeted to intercellular
      adhesion molecule-1 recently was shown to modulate cytokine-inducible target gene
      expression in engrafted human skin. In this study, we examined the route of entry
      into mouse skin of fluorochrome-tagged or naked second-generation 2'-O
      methoxyethyl-modified oligonucleotides that react specifically with an antibody,
      using topical cream-based formulations. In hairless mouse skin,
      immunohistochemical analysis and fluorescence microscopy were unable to detect
      the presence of oligonucleotide in the epidermis or dermis following topical
      application although immunostaining was associated with the stratum corneum and
      fluorescein isothiocyanate-labeled oligonucleotide was observed in hair
      follicles. Kinetic analysis of oligonucleotide topically applied to hair-clipped
      BALB/c mouse skin showed early follicular localization, diffusion of
      oligonucleotide from the mid-follicle, and subsequent dermal accumulation. Saline
      formulation resulted in oligonucleotide remaining within the hair follicle. These
      results suggest that oligonucleotide penetration in skin involves a follicular
      route and further, that topical oligonucleotide therapy may be particularly well
      suited for altering physiology within the hair follicle and related structures.

PMID- 15854039
TI  - Less keratinocyte-derived factors related to more keratinocyte apoptosis in
      depigmented than normally pigmented suction-blistered epidermis may cause passive
      melanocyte death in vitiligo.
AB  - Stem cell factor (SCF) of keratinocyte origin regulates melanocyte growth and
      survival. Deprivation of survival factors causes the apoptosis of melanocytes.
      Vitiligo often develops following physical trauma, even if this is minor. The
      exact mechanism of the Koebner phenomenon in vitiligo is unclear. Apoptosis of
      keratinocytes, which occurs more in depigmented suction-blistered epidermis than
      in the normally pigmented counterpart, could reduce levels of keratinocyte
      derived factors such as SCF and basic fibroblast growth factor (bFGF). Levels of
      SCF expression were examined in the depigmented and normally pigmented paired
      epidermis of 19 patients with vitiligo, and bFGF expression in six patients. The
      expression of SCF (p<0.001) and bFGF was usually reduced in the depigmented
      compared with the normally pigmented epidermis. Apoptosis of cultured normal
      human keratinocytes, which was induced by staurosporine, resulted in a
      concentration-dependent decrease in levels of SCF mRNA and protein. Normal human
      melanocytes proliferated more in medium containing SCF or keratinocyte (XB-2)
      feeder than in medium with neither. Deprivation of SCF or keratinocyte feeder in
      the culture medium induced a marked decrease in melanocytes as a result of
      apoptosis. Therefore, lower expression of keratinocyte-derived factors, including
      SCF, in vitiliginous keratinocytes, which could result from keratinocyte
      apoptosis, might be responsible for passive melanocyte death and may explain the
      Koebner phenomenon.

PMID- 15854040
TI  - In vivo ultrastructural localization of the desmoglein 3 adhesive interface to
      the desmosome mid-line.
AB  - Desmoglein (Dsg) is a cadherin cell-cell adhesion molecule located in desmosomes
      and its precise mechanism for cell-cell adhesion still remains to be elucidated.
      Opposing cadherin molecules may adhere to the N-terminal EC1 domains, or the
      entire length of the extracellular (EC) domains may overlap. To solve this
      controversy, we performed immunoelectron microscopy to map the Dsg3 epitopes in
      desmosomes. Three different hybridoma cell lines producing anti-Dsg3 monoclonal
      antibodies (mAb) were intraperitoneally injected into immunodeficient mice and
      the precise ultrastructural location of bound IgG between the mucosal epithelial
      cells in vivo was statistically measured and analyzed. The binding site of the
      AK23 mAb that recognizes the N-terminal EC1 domain was localized to the electron
      dense mid-line of desmosomes. The binding sites of AK7 and AK18, which recognize
      the C-terminal membrane proximal and middle portions of the EC domains, were
      localized to the desmosomal region proximal to the membrane and the region
      between the plasma membrane and the dense mid-line, respectively. These results
      indicate that the N-terminal regions of Dsg3 from opposing cells interact at the
      dense mid-line of desmosomes where EC1 overlaps.

PMID- 15854041
TI  - Cornulin, a new member of the "fused gene" family, is expressed during epidermal
      differentiation.
AB  - The protein encoded by the C1orf10 gene was described to be esophageal-specific
      and a marker for cancer development. This protein, however, has the previously
      unreported structural features of the "fused gene" family combining sequences and
      structural similarities of both the S100 proteins and precursor proteins of the
      cornified cell envelope as in profilaggrin, trichohyalin, and repetin. Since all
      members of this family are expressed in keratinocytes, we suspected a role in
      epidermal differentiation and named the protein cornulin. Here, we report that
      human cornulin mRNA is expressed primarily in the upper layers of differentiated
      squamous tissues including the epidermis. Using polyclonal peptide antibodies, we
      show that cornulin is expressed in the granular and lower cornified cell layers
      of scalp epidermis and foreskin, as well as in calcium-induced differentiated
      cultured keratinocytes. Ca(2+)-overlay assay indicated that EF-hand domains of
      cornulin are functional and bind calcium. In HeLa cells, cornulin, co-transfected
      with transglutaminase 1, was diffusely distributed throughout the cytoplasm in
      contrast to small proline-rich 4, which localized to the cell periphery. We
      conclude that cornulin is a new member of the "fused gene" family, does not
      appear to be a precursor of the cornified cell envelope by itself, and is a
      marker of late epidermal differentiation.

PMID- 15854042
TI  - Isolation and characterization of human repetin, a member of the fused gene
      family of the epidermal differentiation complex.
AB  - The human repetin gene is a member of the "fused" gene family and localized in
      the epidermal differentiation complex on chromosome 1q21. The "fused" gene family
      comprises profilaggrin, trichohyalin, repetin, hornerin, the profilaggrin-related
      protein and a protein encoded by c1orf10. Functionally, these proteins are
      associated with keratin intermediate filaments and partially crosslinked to the
      cell envelope (CE). Here, we report the isolation and characterization of the
      human repetin gene and of its protein product. The repetin protein of 784 amino
      acids contains EF (a structure resembling the E helix-calcium-binding loop-F
      helix domain of parvalbumin) hands of the S100 type and internal tandem repeats
      typical for CE precursor proteins, a combination which is characteristic for
      "fused" proteins. Repetin expression is scattered in the normal epidermis but
      strong in the acrosyringium, the inner hair root sheat and in the filiform
      papilli of the tongue. Ultrastructurally, repetin is a component of cytoplasmic
      non-membrane "keratohyalin" F-granules in the stratum granulosum of normal
      epidermis, similar to profilaggrin. Finally, we show that EF hands are functional
      and reversibly bind Ca(2+). Our results indicate that repetin is indeed a member
      of the fused gene family similar to the prototypical members profilaggrin and
      trichohyalin.

PMID- 15854043
TI  - Unsaturated fatty acids induce calcium influx into keratinocytes and cause
      abnormal differentiation of epidermis.
AB  - Abnormal follicular keratinization is involved in comedogenesis in acne vulgaris.
      We recently demonstrated that calcium influx into epidermal keratinocytes is
      associated with impaired skin barrier function and epidermal proliferation. Based
      on these results, we hypothesized that sebum components affect calcium dynamics
      in the keratinocyte and consequently induce abnormal keratinization. To test this
      idea, we first observed the effects of topical application of sebum components,
      triglycerides (triolein), saturated fatty acids (palmitic acid and stearic acid),
      and unsaturated fatty acids (oleic acid and palmitoleic acid) on hairless mouse
      skin. Neither triglyceride nor saturated fatty acids affected the skin surface
      morphology or epidermal proliferation. On the other hand, application of
      unsaturated fatty acids, oleic acid, and palmitoleic acid induced scaly skin,
      abnormal keratinization, and epidermal hyperplasia. Application of triglycerides
      and saturated fatty acids on cultured human keratinocytes did not affect the
      intracellular calcium concentration ([Ca(2+)](i)), whereas unsaturated fatty
      acids increased the [Ca(2+)](i) of the keratinocytes. Moreover, application of
      oleic acid on hairless mouse skin induced an abnormal calcium distribution in the
      epidermis. These results suggest that unsaturated fatty acids in sebum alter the
      calcium dynamics in epidermal keratinocytes and induce abnormal follicular
      keratinization.

PMID- 15854044
TI  - Proliferation, cell cycle exit, and onset of terminal differentiation in cultured
      keratinocytes: pre-programmed pathways in control of C-Myc and Notch1 prevail
      over extracellular calcium signals.
AB  - So far it was reported that a switch from low to high extracellular calcium
      induces growth arrest and terminal differentiation in cultured human and mouse
      keratinocytes. We had observed that both canine and mouse keratinocytes
      proliferate in high (1.8 mM, respectively, 1.2 mM) or low (0.09 and 0.06 mM)
      calcium-containing medium. In-depth analysis of this phenomenon revealed, as
      reported here, that the switch between proliferation and terminal differentiation
      occurred irrespective of calcium conditions when the canine and murine
      keratinocytes reach confluency. The "confluency switch" coincided with
      transcriptional upregulation of cell cycle inhibitors p21(WAF1) and p27(KIP1) as
      well as proteins marking onset of terminal differentiation. It was further
      accompanied by downregulation and nuclear clearance of c-Myc, and conversely
      activation of Notch1, which are shown to be critical determinants of this
      process. Together, this study demonstrates that even in the absence of and
      similar to their in vivo environment, cultured canine and mouse keratinocytes
      follow a pre-defined differentiation program. This program is in control of c-Myc
      and Notch1 and does not require complementary signals for onset of terminal
      differentiation except those given by cell-cell contact. Once triggered,
      completion of the terminal differentiation process depends on elevated
      extracellular calcium to stabilize intercellular junctions and components of the
      cornified envelope.

PMID- 15854045
TI  - Regulation of the expression of peptidylarginine deiminase type II gene (PADI2)
      in human keratinocytes involves Sp1 and Sp3 transcription factors.
AB  - Peptidylarginine deiminases (PAD) convert protein-bound arginine residues into
      citrulline residues in a Ca(2+) ion-dependent manner. Among the five isoforms
      (PAD1, 2, 3, 4, and 6) existing in rodents and humans, PAD2 is the most widely
      expressed in both species, tissues, and organs. In order to study the mechanisms
      regulating the expression of the human PAD2 gene, PADI2, we characterized its
      promoter region using transfected human keratinocytes. A series of reporter gene
      constructions derived from the 2 kb region upstream of the transcription
      initiation site defined a minimal promoter sequence from nucleotides -132 to -41.
      This PADI2 region is GC-rich and lacks canonical TATA and CAAT boxes.
      Investigation of cis-acting elements in the region, further deletion analyses and
      electrophoretic mobility shift assays using specific antibodies revealed four Sp1
      binding sites and identified Sp1 and Sp3 as binding factors important for the
      promoter activity. These results suggest that Sp1/Sp3 cooperation may provide a
      mechanism to control the transcription of PADI2.

PMID- 15854046
TI  - The book of opposites: the role of the nuclear receptor co-regulators in the
      suppression of epidermal genes by retinoic acid and thyroid hormone receptors.
AB  - Transcriptional regulation by nuclear receptors occurs through complex
      interactions that involve DNA response elements, co-activators/co-repressors, and
      histone modifying enzymes. Very little is known about how molecular interplay of
      these components may determine tissue specificity of hormone action. We have
      shown previously that retinoic acid (RA) and thyroid hormone (T3) repress
      transcription of a specific group of epidermal keratin genes through a novel
      mechanism that utilizes receptors homodimers. In this paper, we have analyzed the
      epidermal specificity of RA/T3 action by testing the role of co-repressors and co
      activators in regulation of epidermal genes. Using transient co-transfections,
      northern blots, antisense oligonucleotides, and a histone deacetylase (HDAC)
      inhibitor, trichostatin A, we found that in the context of specific keratin RE
      (KRE), co-activators and histone acetylase become co-repressors of the RA/T3
      receptors in the presence of their respective ligands. Conversely, co-repressors
      and HDAC become co-activators of unliganded T3Ralpha. The receptor-co-activator
      interaction is intact and occurs through the NR-box. Therefore, the role of co
      activator is to associate with liganded receptors whereas the KRE-receptor
      interaction determines specific transcriptional signal, in this case repression.
      This novel molecular mechanism of transcriptional repression conveys how RA and
      T3 target specific groups of epidermal genes, thus exerting intrinsic tissue
      specificity.

PMID- 15854047
TI  - Osteopontin expression correlates with melanoma invasion.
AB  - Melanoma is one of the most aggressive cancers affecting humans. Although early
      melanomas are curable with surgical excision, metastatic melanomas are associated
      with high mortality. The mechanism of melanoma development, progression, and
      metastasis is largely unknown. In order to uncover genes unique to melanoma
      cells, we used high-density DNA microarrays to examine the gene expression
      profiles of metastatic melanoma nodules using benign nevi as controls. Over 190
      genes were significantly overexpressed in metastatic melanomas compared with
      normal nevi by at least 2-fold. One of the most abundantly expressed genes in
      metastatic melanoma nodules is osteopontin (OPN). Immunohistochemistry staining
      on tissue microarrays and individual skin biopsies representing different stages
      of melanoma progression revealed that OPN expression is first acquired at the
      step of melanoma tissue invasion. In addition, blocking of OPN expression by RNA
      interference reduced melanoma cell numbers in vitro. Our observations suggest
      that OPN may be acquired early in melanoma development and progression, and may
      enhance tumor cell growth in invasive melanoma.

PMID- 15854048
TI  - Upregulation of the IFN-gamma-stimulated genes in the development of delayed
      pigmented spots on the dorsal skin of F1 mice of HR-1 x HR/De.
AB  - DNA microarray hybridization was used to measure the changes of mRNA levels over
      time during the development of delayed pigmented spots on the dorsal skin of F1
      mice of HR-1 x HR/De. Upregulation of a number of interferon (IFN)-gamma
      stimulated genes was detected in delayed pigmented lesions, suggesting that IFN
      gamma may play a pivotal role in the development of delayed pigmented spots in
      this model. Upregulation of these genes was further supported by the increased
      protein expression level of IFN-gamma in the lesions. Epidermal infiltration of
      CD8(+) T lymphocytes and mast cell accumulation in the dermis were observed in
      delayed pigmented spots. Genes encoding chemokines such as monocyte
      chemoattractant protein-2 (MCP-2), IFN-inducible protein 10 (IP-10), and monokine
      induced by IFN-gamma (MIG) were among those upregulated by IFN-gamma. We
      hypothesize that chemokines produced in the epidermis induce migration of
      inflammatory cells, such as T lymphocytes, mast cells, and macrophages, to the
      vicinity of melanocytes. Keratinocytes, T lymphocytes, mast cells, and
      macrophages would become involved in an interactive network, providing a suitable
      local environment for melanocyte activation. In this environment, melanocytes are
      exposed to an extensive array of secreted mediators. Reciprocal activation among
      these cells to maintain this interactive network results in constitutive
      melanocyte activation and chronic melanin synthesis in delayed pigmented lesions.

PMID- 15854049
TI  - Late cornified envelope family in differentiating epithelia--response to calcium
      and ultraviolet irradiation.
AB  - The late cornified envelope (LCE) gene cluster within the epidermal
      differentiation complex on human chromosome one (mouse chromosome three) contains
      multiple conserved genes encoding stratum-corneum proteins. Within the LCE
      cluster, genes form "groups" based on chromosomal position and protein homology.
      We link a recently accepted nomenclature for the LCE cluster (formerly XP5, small
      proline-rich-like, late-envelope protein genes) to gene structure, groupings, and
      chromosomal organization, and carry out a pan-cluster quantitative expression
      analysis in a variety of tissues and environmental conditions. This analysis
      shows that (i) the cluster organizes into two "skin" expressing groups and a
      third group with low-level, tissue-specific expression patterns in all barrier
      forming epithelia tested, including internal epithelia; (ii) LCE genes respond
      "group-wise" to environmental stimuli such as calcium levels and ultraviolet (UV)
      light, highlighting the functional significance of groups; (iii) in response to
      UV stimulation there is massive upregulation of a single, normally quiescent, non
      skin LCE gene; and (iv) heterogeneity occurs between individuals with one
      individual lacking expression of an LCE skin gene without overt skin disease,
      suggesting LCE genes affect subtle attributes of skin function. This quantitative
      and pan-cluster expression analysis suggests that LCE groups have distinct
      functions and that within groups regulatory diversification permits specific
      responsiveness to environmental challenge.

PMID- 15854050
TI  - An action spectrum for the production of cis-urocanic acid in human skin in vivo.
AB  - Urocanic acid (UCA) is present at millimolar concentrations in mammalian
      epidermis and undergoes photoisomerization from the naturally occurring trans
      isomer to the cis-isomer on exposure to ultraviolet radiation (UVR). Cis-UCA
      causes downregulation of various immune responses in mouse and human experimental
      models and has been proposed as both a chromophore and a mediator of UV-induced
      immune suppression. In this study, the wavelength dependence from 260-340 nm for
      trans to cis-UCA photoisomerization in human skin was analyzed in five healthy
      volunteers. The resulting action spectrum demonstrated maximal cis-UCA production
      in the UVB spectral region of 280-310 nm. This spectral peak is red-shifted to
      longer wavelengths compared with the erythemal action spectrum. The cis-UCA
      action spectrum can be used to predict the ability of sunscreens to protect
      against UVR-induced cis-UCA formation and may assist in explaining discrepancies
      between sunscreens' abilities to protect against erythema and
      photoimmunosuppression.

PMID- 15854051
TI  - UVB irradiation increases the release of SCF from human epidermal cells.

PMID- 15854052
TI  - Sun protection, vitamin D deficiency, and management of cutaneous oncology in
      organ transplant recipients (OTR).

PMID- 15854053
TI  - Variation in skin thickness may explain some of the within-person variation in
      ultraviolet radiation-induced erythema at different body sites.

PMID- 15854054
TI  - Proportion of lifetime UV dose received by age 18, what Stern et al actually said
      in 1986.

PMID- 15854056
TI  - Reporting Hardy-Weinberg tests in case-control studies: reasons for caution but
      not for panic reactions.

PMID- 15854055
TI  - Vitamin D induces the antimicrobial protein hCAP18 in human skin.

PMID- 15854057
TI  - A novel deletion mutation in keratin 5 causing the removal of 5 amino acids and
      elevated mutant mRNA levels in Dowling-Meara epidermolysis bullosa simplex.

PMID- 15854058
TI  - Single nucleotide polymorphisms of the fibroblast growth factor receptor 2 gene
      in patients with chronic venous insufficiency with leg ulcer.

PMID- 15854059
TI  - Increased serum CCL28 levels in patients with atopic dermatitis, psoriasis
      vulgaris and bullous pemphigoid.

PMID- 15854060
TI  - Cultured cells from the adult human hair follicle dermis can be directed toward
      adipogenic and osteogenic differentiation.

PMID- 15854062
TI  - Probing the causes of visual acuity loss in patients diagnosed with functional
      amblyopia.

PMID- 15854063
TI  - Possible contraindications and adverse reactions associated with the use of
      ocular nutritional supplements.
AB  - The role of oxidation in the development of age-related eye disease has prompted
      interest in the use of nutritional supplementation for prevention of onset and
      progression. Our aim is to highlight possible contraindications and adverse
      reactions of isolated or high dose ocular nutritional supplements. Web of Science
      and PubMed database searches were carried out, followed by a manual search of the
      bibliographies of retrieved articles. Vitamin A should be avoided in women who
      may become pregnant, in those with liver disease, and in people who drink
      heavily. Relationships have been found between vitamin A and reduced bone mineral
      density, and beta-carotene and increased risk of lung cancer in smoking males.
      Vitamin E and Ginkgo biloba have anticoagulant and anti-platelet effects
      respectively, and high doses are contraindicated in those being treated for
      vascular disorders. Those patients with contraindications or who are considered
      at risk of adverse reactions should be advised to seek specialist dietary advice
      via their medical practitioner.

PMID- 15854064
TI  - Systemic associations of retinal microvascular signs: a review of recent
      population-based studies.
AB  - Retinal microvascular signs, such as generalized retinal arteriolar narrowing,
      focal arteriolar narrowing, arteriovenous nicking and retinal haemorrhages,
      microaneurysms and cotton wool spots, are common fundus findings in the general
      population, even in individuals without hypertension or diabetes. Recent
      population-based studies have provided new insights into the systemic
      associations and clinical significance of these retinal signs. Studies show that
      these retinal microvascular signs are strongly associated with elevated blood
      pressure (BP). Generalized retinal arteriolar narrowing may be associated with
      markers of inflammation and risk of diabetes and hypertension. Retinal
      haemorrhages, microaneurysms and cotton wool spots are associated with risk of
      subclinical and clinical stroke, cognitive impairment, renal dysfunction and
      cardiovascular mortality, independent of BP and cardiovascular risk factors. A
      consistent pattern of association between retinal microvascular signs and
      ischaemic heart disease has not been demonstrated. This suggests that patients
      with some retinopathy signs (retinal haemorrhages, microaneurysms and cotton wool
      spots) may benefit from a careful systemic evaluation and, if supported by
      further research, appropriate risk reduction therapy.

PMID- 15854065
TI  - The validity of a digital eyelid tonometer (TGDc-01) and its comparison with
      Goldmann applanation tonometry - a pilot study.
AB  - PURPOSE: To determine the intra- and inter-examiner repeatability of a new eyelid
      tonometer, and its agreement with Goldmann applanation tonometry (GAT). MATERIALS
      AND METHODS: Forty normal subjects were recruited and their intraocular pressure
      was measured by two examiners using the eyelid tonometer. Examiner 1 carried out
      the first set of measurement, followed by examiner 2, and then examiner 1 again.
      Finally, a third examiner was responsible for GAT measurement. Five readings were
      obtained from the eyelid tonometer by each examiner each time and were masked,
      and three readings were obtained from GAT. The mean readings from the eyelid
      tonometer and GAT were used for analysis. RESULTS: The intra-examiner
      repeatability for the eyelid tonometer was better (around +/-5 mmHg 95% of the
      cases) than the inter-examiner repeatability (around +/-8 mmHg 95% of the cases).
      The mean difference between the eyelid tonometer and GAT was small from examiner
      1 (<0.5 mmHg). However, the limits of agreement were greater than the clinically
      acceptable level of +/-3 mmHg. Examiner 2 gave an even greater difference from
      GAT. CONCLUSIONS: Similar to other recent studies, we have found that this eyelid
      tonometer does not provide good agreement with GAT. Different examiners could
      position the instrument differently and this eyelid tonometer is suggested for
      screening purposes only.

PMID- 15854066
TI  - Distance vergence adaptation is abnormal in subjects with convergence
      insufficiency.
AB  - It is well known that in convergence insufficiency (CI) prism adaptation is
      reduced in response to base-out (BO) prisms at near. There have also been some
      suggestions in the literature that adaptation is reduced at other distances as
      well. The present data show that in CI adaptation is not only reduced in response
      to BO at near, but also in response to base-in (BI) at near and for both BI and
      BO at distance. This raises the interesting question whether distance adaptation
      becomes reduced because of reduced near adaptation or whether these subjects have
      a generally reduced horizontal adaptation mechanism.

PMID- 15854067
TI  - Horizontal and vertical prism adaptation are different mechanisms.
AB  - As part of a study on subjects with convergence insufficiency (CI), their
      vertical and horizontal vergence adaptation was assessed and compared with age
      matched controls in order to investigate whether the horizontal adaptation system
      can be regarded as being independent of the vertical adaptation system. Using a
      flashed Maddox rod technique horizontal vergence adaptation was found to be
      reduced in CI subjects whereas no difference could be found in vertical
      adaptation. These results confirm that the vertical and horizontal adaptation
      systems can be treated as independent mechanisms.

PMID- 15854068
TI  - Visual experience during cataract surgery: a nation-wide survey on the knowledge
      of optometry students.
AB  - PURPOSE: Many patients experience a variety of visual sensations during cataract
      surgery under local anaesthesia. Up to 16.2% of patients are frightened by their
      intraoperative visual experience. This study aimed to determine the knowledge and
      beliefs of optometry students on this subject. METHODS: A nationwide survey using
      a standardised, self-administered questionnaire was conducted on all optometry
      students in Singapore. RESULTS: For cataract surgery under regional anaesthesia,
      38.9% of the respondents believed that patients might experience no light
      perception while 68.5% felt that patients were likely to be able to perceive
      light. Overall, 70.4% felt that patients might be frightened by their visual
      experiences and 88.0% believed that preoperative counselling of patients would
      serve to reduce the fear experienced during the surgery. For cataract surgery
      under topical anaesthesia, 37.0% of the respondents believed that patients would
      perceive no light and 74.1% believed that patients would retain light perception.
      Overall, 67.6% believed that patients may be frightened and 86.1% felt that
      preoperative counselling would help. CONCLUSION: Many optometry students
      correctly believed that patients might experience a variety of visual sensations
      during cataract surgery under local anaesthesia. The majority were also aware
      that patients might be frightened by this and felt that preoperative counselling
      would be helpful.

PMID- 15854069
TI  - The detection of small relative simulated field defects using multifocal VEPs.
AB  - INTRODUCTION: The multifocal visual-evoked potential (mfVEP) has been widely used
      in the study of diseases of the visual system. However, the sensitivity of the
      mfVEP in the objective detection of relative field defects has not been
      determined. This study investigates variations in mfVEP responses while
      simulating relative field defects by using different luminous transmission masks
      [neutral density (ND) filters] on the stimulus pattern. METHODS: Simulated
      relative field defects with four different luminous transmissions were obtained
      by using 0.2, 0.4, 0.6, and 0.8 ND filters, 5 degrees in size, at two different
      retinal eccentricities (10 and 16 degrees) on a standard mfVEP dartboard
      stimulus. Eleven normal subjects were recruited for mfVEP measurements. The
      response amplitudes and latencies of the N1 and P1 of the mfVEP, with and without
      small simulated relative field defects, were compared. RESULTS: The mfVEP
      amplitudes of N1 and P1 decreased substantially when 0.6 and 0.8 ND filters were
      introduced. The effects were similar at both the 10- and 16-degree eccentricities
      but there was no change in latency with simulated field defects at either
      location. CONCLUSIONS: The mfVEP can detect a simulated relative field defect 5
      degrees in size starting with 0.6 log unit reduction in luminance at both 10
      degree and 16-degree eccentricities. This illustrates that the sensitivity of the
      mfVEP measurement is nearly comparable with that of the Humphrey Visual Field
      Analyser.

PMID- 15854070
TI  - Frequency doubling technology perimetry and standard automated perimetry in
      migraine.
AB  - The literature suggests that visual field defects may be more common in people
      who experience migraine. The Humphrey frequency doubling (FDT) visual field
      instrument selectively examines the magnocellular visual pathway, but has not
      previously been used to investigate visual function in migraine. In a masked
      controlled study we compared Humphrey FDT and Humphrey Swedish Interactive
      Threshold Algorithm fields of 25 migraine sufferers with 25 age- and gender
      matched controls. Although both mean deviation and pattern standard deviation
      were a little worse in the migraine group, these differences did not reach
      statistical significance. There were no inter-eye visual field differences in the
      migraine group compared with controls. Comparing the mean of all the contrast
      thresholds in each hemisphere, there were no more inter-hemifield visual field
      differences in the migraine group compared with controls. There was no
      significant difference between the migraine and control groups in intra-ocular
      pressures. The visual field parameters were not correlated with the interval
      since the last migraine headache, the severity of migraine headache, the duration
      of migraine headache or the number of migraine headaches per annum. In our data,
      there was no evidence of visual field deficits, a magnocellular deficit, or
      indications of glaucomatous pathology.

PMID- 15854071
TI  - The pupillary light reflex in migraine.
AB  - The literature suggests that there may be pupil size and response abnormalities
      in migraine headache sufferers. We used an infra-red pupillometer to measure
      dynamic pupil responses to light in 20 migraine sufferers (during non-headache
      periods) and 16 non-migraine age and gender matched controls. There was a
      significant increase in the absolute inter-ocular difference of the latency of
      the pupil light response in the migraine group compared with the controls (0.062
      s vs 0.025 s, p = 0.014). There was also a significant correlation between
      anisocoria and lateralisation of headache such that migraine sufferers with a
      habitual head pain side have more anisocoria (r = 0.59, p < 0.01), but this was
      not related to headache laterality. The pupil changes were not correlated with
      the interval since the last migraine headache, the severity of migraine headache
      or the number of migraine headaches per annum. We conclude that subtle
      sympathetic and parasympathetic pupil abnormalities persist in the inter-ictal
      phase of migraine.

PMID- 15854072
TI  - Corneal mechanical sensitivity measurement using a staircase technique.
AB  - PURPOSE: To determine the repeatability of an unequal staircase technique (Garcia
      Perez Staircase, GPS) to measure corneal mechanical threshold using the CRCERT
      belmonte Aesthesiometer, and to compare this with a previously-reported
      psychophysical method (method of constant stimuli, MOCS). METHODS: The GPS,
      utilising unequal ascending and descending steps, was used to obtain a threshold
      measurement from the mean of six response reversals. repeatability was determined
      for the GPS and MOCS methods (N = 14), and threshold results obtained with each
      method were compared (N = 10). RESULTS: The GPS (65.0 +/- 16.9 mL min(-1); CoR +/
      18.3 mL min(-1)) method was more repeatable than the MOCS (64.0 +/- 15.7 mL min(
      1); CoR +/- 37.3 mL min(-1)) and the absolute values obtained with the two
      methods were not significantly different. CONCLUSIONS: Although each method gave
      equivalent threshold results, the GPS method was more repeatable and quicker to
      apply and hence should reduce the influence of patient fatigue and help to
      minimise possible carry-over effects.

PMID- 15854073
TI  - In vivo corneal confocal microscopy in keratoconus.
AB  - PURPOSE: To evaluate the corneas of keratoconic subjects using in vivo confocal
      microscopy. METHODS: Slit scanning confocal microscopy was used to evaluate the
      central cornea of one eye of each of 29 keratoconic subjects (mean age 31 +/- 10
      years; range 16-49 years). Quantitative aspects of corneal morphology were
      compared against data from control subjects. RESULTS: Compared with normal
      control corneas, epithelial wing cell nuclei were larger (p < 0.0001) and
      epithelial basal cell diameter was larger (p < 0.05) in the keratoconic cornea.
      Many of the keratoconic corneas investigated showed increased levels of stromal
      haze and reflectivity, which appeared to be related to the presence of apical
      scarring on slit lamp examination. A grading scale was devised to quantify the
      levels of haze. This scale was shown to provide a measure of the level of
      scarring present. The anterior keratocyte density (AKD) and posterior keratocyte
      density were 19% lower (p < 0.0001) and 10% lower (p = 0.004) than in controls,
      respectively. The reduction in AKD was significantly associated with three
      factors: a history of atopy, eye rubbing and the presence of corneal staining.
      The mean endothelial cell density in keratoconus was 6% greater than that of
      normal controls (p = 0.05). The level of endothelial polymegethism was shown not
      to be different between keratoconic subjects and matched controls (paired t-test:
      t = 1.82, p = 0.08). CONCLUSIONS: Confocal microscopy demonstrates significant
      quantitative alterations of corneal morphology in keratoconus.

PMID- 15854074
TI  - Microbiological analysis of chronic dacryocystitis.
AB  - AIMS: To investigate the microbiology of specimens from patients with chronic
      dacryocystitis. METHODS: A total of 100 samples were obtained from the contents
      of the lacrimal duct in 91 consecutive patients with chronic dacryocystitis,
      including nine bilateral cases. These samples were cultured for aerobic and
      anaerobic bacteria and fungi with a routine microbiological technique. Positive
      cultured isolates were identified. RESULTS: A total of 180 strains were isolated
      from the 85 bacterial samples, including 150 strains of aerobic bacteria and 30
      strains of anaerobic bacteria. Fungi were found in eight samples and actinomyces
      in three samples. The bacterial species that were most frequently found were
      Staphylococcus species, representing 34.5% of all strains, followed by
      Corynebacterium diphtheroides (15.5%). The sensitivity tests revealed that levo
      ofloxacin and amikacin were the most effective antibiotics. CONCLUSIONS: Gram
      positive cocci was the predominant pathogen of chronic dacryocystitis. Levo
      ofloxacin and amikacin had the best effect in vitro.

PMID- 15854075
TI  - White lesion in the corneal pigmented ring associated with orthokeratology.
AB  - The development of the pigmented corneal arc and a white lesion near the inner
      margin of the arc in a girl wearing overnight orthokeratology (ortho-k) lenses
      for myopic control is reported. The girl was examined before and followed up
      every 6 months after the treatment over a 3-year period. The initial spherical
      equivalent refractive error and keratometric readings (flattest/steepest
      meridians) were -2.37 D and 45.00 D/46.75 D respectively in the right eye and 
      3.12 D and 45.25 D/46.00 D respectively in the left eye. She was wearing ortho-k
      lenses of a four-zone design made of Boston XO material on a nightly basis. The
      same lens design was used throughout the monitoring period. Corneal topography
      showed a rather well-centred treatment zone but vision varied between visits
      because of fluctuations in residual refractive error. The corneal condition of
      each eye was unremarkable except for the presence of the pigmented corneal arc
      first observed 6 months after the commencement of the treatment. The intensity of
      the arc did not change over the years in the right eye but increased in the left
      eye. A faint white lesion within the inner border of the left pigmented arc was
      first observed at the end of the second year and it became more obvious at the
      end of the third year. This lesion appears to be similar to those reported in
      intense Fleischer's rings associated with keratoconus. Although the presence of
      the arc may have no clinical ramification, the change in the intensity and the
      development of the white lesion may reflect an increased stress exerted on the
      cornea with continued ortho-k lens wear.

PMID- 15854076
TI  - How precise do precision tints have to be and how many are necessary?
AB  - Among those individuals who habitually wear precision tints, reading speed can
      vary as a function of the chromaticity of the illuminating light. The reading
      speed decreases as the chromaticity departs from optimum, whether in saturation
      or in hue. When the distance in the CIE 1976 UCS diagram between the chromaticity
      of the illuminating light and that optimal for reading exceeds about 0.08, the
      colour has little residual benefit. We attempt to answer two questions
      numerically: (1) how is reading speed affected by the variation in the colour
      provided by the tint under different lighting conditions? (2) how many different
      tints does an ophthalmic tinting system need to be able to provide? Analysis of
      1000 recent prescriptions suggests that, for most, the variation in colour with
      illumination is sufficient to reduce, but not eliminate, the beneficial effects
      of the tints. The number of trial tints required by an ophthalmic tinting system
      is a power function of the degree of efficacy desired, and for an average
      efficacy >95% of optimum, the number of trial tints needs to exceed 1000. In
      practice this requirement can readily be achieved by combining trial lenses and
      by appropriate dyeing techniques.

PMID- 15854077
TI  - Caught between a rock and the Data Protection Act.

PMID- 15854078
TI  - Baseline flow in coronary bypass grafts.
AB  - BACKGROUND: The purpose of the study is to estimate the total blood flow in
      coronary artery bypass grafts. METHODS: In a 3-year period 102 patients having a
      standardized coronary artery bypass grafting (CABG) with the left internal
      mammary artery (LIMA) anastomosed to the left anterior descending artery and a
      sequential vein grafted to the remaining diseased coronary arteries were included
      in the study, 21 females and 81 males. In females a mean of 3.9 anastomosis
      (range 2-5) were performed and in males a mean of 4.2 (range 2-6) were performed.
      Flow in the bypass grafts was measured with the transit-time method before
      termination of cardiopulmonary bypass. RESULTS: Females: LIMA 31 mL/min, vein
      graft 74 mL/min (26 mL/min per anastomosis), cumulated flow 105 mL/min. Males:
      LIMA 31 mL/min, vein graft 93 mL/min (29 mL/min per vein anastomosis), cumulated
      flow 124 mL/min. CONCLUSION: Conventional CABG may restore half of the normal
      resting coronary artery blood flow (250 mL/min).

PMID- 15854079
TI  - Does mediastinitis affect the graft patency?
AB  - As inflammation began to be recognized as a major contributor to the pathogenesis
      of atherosclerosis, we evaluated the patients that developed mediastinitis, a
      long-standing inflammatory process, after coronary artery bypass grafting. There
      are many studies that have focused on the graft patency. But, till now, no study
      has been done to detect the effects of mediastinitis to graft patency. So, we
      aimed to detect the effect of mediastinitis on the graft patency in patients who
      have undergone coronary artery bypass surgery. Sixteen of 45 patients who have
      been operated upon for coronary artery bypass surgery and developed
      mediastinitis, which was treated with open drainage and mediastinal irrigation
      with late wound closure, were included in the study. The mean age of the patients
      was 55 +/- 11 (range 35-69) and nine of the patients were male. The graft patency
      was evaluated with control coronary angiographies after a mean period of 30.42 +/
      43.17 months (range 1-132). The left internal thoracic artery was patent in all
      patients (100%). Right internal thoracic artery patency rate was 50% (1/2). One
      individual bypassed radial artery was patent, whereas the sequential bypassed
      graft was occluded. The patency ratio of radial artery anastomosis was 33% (1/3).
      Twelve of the 17 saphenous vein grafts were patent (70.58%). The total number of
      patent distal anastomosis was 30/38 (78.94%). When compared with the graft
      patency of patients without infection, it was found that mediastinitis does not
      affect the graft patency rates adversely.

PMID- 15854080
TI  - Survival and quality of life after cardiac surgery complicated by prolonged
      intensive care.
AB  - AIM: To determine survival, factors determining survival and evaluate quality of
      life (QOL) after 1 year, in patients who had prolonged intensive care unit (ICU)
      stay after cardiac surgery. METHODS: In the year 2001, 804 patients underwent
      various cardiac procedures utilising cardiopulmonary bypass (CPB). Eighty-nine
      consecutive patients requiring ICU stay of > or = 5 days constituted the study
      group, majority of these suffered from multiorgan failure (> 2 organ systems).
      Survival was determined in the study group after 1 year. Patients with an
      uncomplicated postoperative course were matched to the survivors in the study
      group with respect to age, gender, type of surgery, risk scores, and duration of
      follow-up and constituted the control group. The, Short Form Health Survey was
      used to assess QOL at the end of 1 year in these patients. QOL was compared
      between the study group and the control group and to that of general population.
      RESULTS: Seventy percent of the patients in the study group suffered from failure
      of at least three organ systems. Mean ICU stay was 13 +/- 3 days (median nine,
      maximum 53). At the end of 1 year the mortality in the study group was 34%. The
      independent predictors of mortality were: preoperative cardiac support, lower
      ejection fraction, higher Parsonnet score, higher Euroscore, pulmonary
      complications, renal failure necessitating hemofiltration, CNS complications, and
      failure of three or more organ systems. The QOL was lower in the study group than
      the control group in all eight dimensions measured (significant in five p <
      0.05): Physical function, Role physical, Vitality, Mental health, General health,
      and Bodily pain. CONCLUSION: One year mortality in patients with prolonged ICU
      stay after cardiac surgery remains high. Identification of risk factors will help
      to reduce the mortality with help of regular follow up. The QOL remains low in
      all dimensions especially those measuring physical aspects and pain.

PMID- 15854081
TI  - Management of intractable sternal wound infections with topical negative pressure
      dressing.
AB  - BACKGROUND: Sternal osteomyelitis after cardiac surgery is a life-threatening
      complication. The potential spread of infection into the mediastinum, involving
      the prosthetic valve, grafts, and suture lines, makes this an extremely serious
      complication confronting both cardiac and plastic surgeons. AIM: Topical negative
      pressure (TNP) dressing has been proven to be effective for wound healing. We
      want to take advantages of this equipment to improve the results of intractable
      sternal wound infection. The results are discussed. METHODS: From December 1996
      to July 2002, 25 patients with sternal wound infections were treated at Kaohsiung
      Medical University Hospital. Nine patients suffering intractable sternal
      osteomyelitis were managed with debridement and TNP dressings. These patients
      received 1-3 debridements (an average of 2.2 debridements), and the average TNP
      dressing treatment period was 20.2 days (ranging from 3 to 43 days). After
      management, the infections were controlled and healthy vascularized wounds were
      achieved. Then, flap reconstruction could be performed for complete wound
      closure. Seven of the nine patients survived, and there was no recurrence of
      sternal osteomyelitis during follow-up period (ranging from 5 to 70 months).
      CONCLUSION: The advantages of applying TNP dressings in cases of intractable
      sternal wound infections include (1) protecting the underlying mediasternal
      structure from infection, (2) permitting delayed sternal closure to avoid cardiac
      compression induced compromised cardiopulmonary function, (3) possibility of
      repeated wound inspection and bedside debridement, (4) cost-effectiveness of
      wound care, and (5) providing an option to promote sternal wound secondary
      healing for patients in poor physical condition.

PMID- 15854082
TI  - Changing surgical management for acute aortic dissections type a improves
      immediate outcomes.
AB  - BACKGROUND: Surgical treatment of acute aortic dissection type A is well
      established. This study analyzes the impact of changing surgical management of
      Type A dissections on hospital mortality and postoperative complications. METHOD:
      Between January 1980 and December 2002, 141 consecutive patients were operated
      for acute Type A aortic dissection. Patients were analyzed in 3 time periods;
      1980-1989, n = 26, 1990-1999, n = 71 and 2000-2002, n = 44). Antegrade cerebral
      perfusion via subclavian cannulation, a more extensive resection as well as
      valvar repair was introduced as routine procedures from January 2000. RESULTS:
      Mortality and neurological complications decreased over time; from 31% to 9.1%
      and from 27% to 2.5%, respectively. During follow-up, 14 patients (12%) required
      surgical re-intervention for aneurysms (1 to 17 years later) with associated
      hospital mortality of 21%. CONCLUSIONS: Antegrade cerebral perfusion reduces
      neurological complications and more extensive surgical approach did not increase
      mortality and morbidity.

PMID- 15854083
TI  - LDH levels and left atrial ultrastructural chances in patients with mitral
      paraprosthetic regurgitation.
AB  - BACKGROUND AND AIM: The aim of this study was to assess the effect of
      paraprosthetic regurgitation of mitral mechanical valves to myocardial tissue and
      lactate dehydrogenase (LDH) level. METHODS: We compared 19 patients (study group)
      who had mitral mechanical valve with severe mitral paravalvular regurgitation
      with 20 patients (control group) who had native valve with severe rheumatic
      mitral regurgitation. None of the patients had clinical hemolytic anemia. On
      transesophageal echocardiographic examination, semiquantative evaluation and
      spatial distribution of regurgitant jets were noted in both of the groups. Five
      LDH isoenzymes were studied in two groups. Myocardial tissue specimens were taken
      from the left atrial wall during reoperation. Grids randomly taken were studied
      under the transmission electron microscope. RESULTS: Total serum LDH levels of
      the study group (578 +/- 12 IU/L) were higher than the control group (495 +/- 6.2
      IU/L) (p < 0.001). We found LDH1/LDH2 more than 1 in all patients; the ratio was
      not statistically different in the control group. Electron microscopy revealed
      the same degree of injury in both groups. Haptoglobin levels were decreased and
      reticulocyte counts were increased in patients with paraprosthetic valve
      regurgitation. CONCLUSIONS: Electron microscopic findings support that myocardial
      injury contributes to increase of total LDH level and high LDH1/LDH2 ratio. But
      statistically significant elevation in total LDH level in study group and the
      stable state of LDH1/LDH2 ratio between two groups showed that hemolysis caused
      by paraprosthetic regurgitation is the most important factor for the increase of
      total LDH level, so that high LDH level can be used as a reliable parameter for
      the diagnosis of intravascular hemolysis in paraprosthetic regurgitation.

PMID- 15854084
TI  - Simultaneous carotid and coronary arteries disease: staged or combined surgical
      approach?
AB  - BACKGROUND: Patients suffering from a concomitant coronary and carotid artery
      occlusive disease represent a high-risk population whose management remains
      controversial. METHODS: Between April 1979 and June 2002, 202 patients (163 men
      and 39 women, mean age 65 +/- 7 years) were admitted at the Department of
      Cardiovascular Surgery of the University of Bologna for coronary artery bypass
      graft and carotid endarterectomy (CEA). In Group 1 (140 patients) coronary artery
      bypass graft and carotid endarterectomy were performed simultaneously while in
      Group 2 (62 patients) they were performed as two-staged procedures. RESULTS: The
      rate of postoperative stroke was 6.4% in Group 1 (9/140) and 4.8% in Group 2
      (3/62). Significant univariate predictors of myocardial infarction were smoking
      history and previous myocardial infarction; for stroke they were older, greater
      than 70 years, and a smoking history; for death the significant predictors were
      the operative approach, the low ejection fraction, smoking history, renal
      failure, and peripheral vascular occlusive disease. The hospital mortality was
      6.4% in Group 1 versus 12.9% in Group 2. CONCLUSIONS: Despite the highly selected
      populations, the contemporary surgical results indicate that the management of
      these patients needs careful pre-, intra-, and postoperative assessment and
      timing aimed at reducing the ischemic injuries, both cerebral and cardiac,
      therefore we believe that the surgical technique should be individualized for
      each patient.

PMID- 15854085
TI  - Effects of ischemic preconditioning in human heart.
AB  - BACKGROUND: The aim of this study is to investigate the effects of ischemic
      preconditioning (IP) on myocardium and the level of nitric oxide (NO) in patients
      undergoing aorta-coronary bypass surgery. METHODS: Twenty consecutive patients
      with coronary artery disease were subjected into two equal groups; the IP group
      and the control group. Following the onset of cardiopulmonary bypass in the study
      group, hearts were preconditioned with two 3-minute periods of cross-clamping
      separated by 2 minutes of reperfusion. In the control group, cardiopulmonary
      bypass was continued for 10 minutes without using cross-clamp. Arterial and
      coronary sinus blood samples were used to determine serum NO, malondialdehyde
      (MDA), creatine phosphokinase-MB (CKMB), and lactate dehydrogenase (LDH) levels.
      Need for defibrillation after cross-clamp removal, ECG changes, postoperative
      arrhythmias, ejection fraction, and fractional shortening rates were recorded as
      hemodynamic data. RESULTS: Serum NO level was higher in the study group 5 minutes
      after aortic clamp removal (199.3 +/- 92.7 vs. 112.2 +/- 35.8 micromol; p = 001).
      Serum MDA (2.55 +/- 0.4 vs. 4.06 +/- 0.5; etamol/ml; 5 minutes after the aortic
      clamp removal; p = 0.0002); CK-MB (22.8 +/- 2.5 vs. 37.4 +/- 4.1; U/L 12 hours
      after the operation, p < 0.0001), and LDH (501.8 +/- 46.7 vs. 611.4 +/- 128.3;
      IU/L 48 hours after the operation, p = 0.02) levels were significantly lower in
      the preconditioned group when compared with the control group. Also, need for
      electrical defibrillation was significantly lower in the study group; Ejection
      fraction (64.3 +/- 6.3 vs. 57.6 +/- 7.6; p = 0.04) and fractional shortening
      (31.7 +/- 3.9 vs. 26.2 +/- 4.0; p = 0.04) rates were better in the study group
      postoperatively. CONCLUSIONS: These data may suggest that cardioprotection by
      ischemic preconditioning offers higher NO production, a lower myocardial
      ischemia, and better functional recovery of the hearts in coronary artery surgery
      patients.

PMID- 15854086
TI  - Does robotic technology make minimally invasive cardiac surgery too expensive? A
      hospital cost analysis of robotic and conventional techniques.
AB  - BACKGROUND: While potential benefits of robotic technology include decreased
      morbidity and improved recovery, some have suggested a prohibitively high cost.
      This study was undertaken to compare actual hospital costs of robotically
      assisted cardiac procedures with conventional techniques. METHODS: We conducted a
      retrospective review of clinical and financial data of 20 patients who underwent
      atrial septal defect (ASD) closure and 20 patients who underwent mitral valve
      repair (MVr) using either robotic techniques or a conventional approach with a
      sternotomy. Total hospital cost (actual resource consumption) was subdivided into
      operative and postoperative costs. RESULTS: Robotic technology did not
      significantly increase total hospital cost for ASD closure or MVr (p = 0.518 and
      p = 0.539). However, when including the initial capital investment for the robot
      through amortization of institutional costs, total hospital cost was increased by
      $3,773 for robotic ASD closure and $3,444 for robotic MVr (p = 0.021 and p =
      0.004). The major driver of cost for robotic cases (operating room time)
      decreased over time. CONCLUSIONS: Robotic technology did not significantly
      increase hospital cost. While the absolute cost for robotic surgery was higher
      than conventional techniques after taking into account the institutional cost of
      the robot, the major driver of cost for robotic procedures will likely continue
      to decrease, as the surgical team becomes increasingly familiar with robotic
      technology. Furthermore, other benefits, such as improvement in postoperative
      quality of life and more expeditious return to work may make a robotic approach
      cost-effective. Thus, it is possible that the benefits of robotic surgery may
      justify investment in this technology.

PMID- 15854087
TI  - The effect of oral prednisolone with chronic obstructive pulmonary disease
      undergoing coronary artery bypass surgery.
AB  - BACKGROUND: Chronic obstructive pulmonary disease is still one of the most
      important problems in patients undergoing cardiopulmonary bypass. The purpose of
      this prospective study was to assess the beneficial effects of oral prednisolone
      on pulmonary functions in patients undergoing cardiopulmonary bypass. METHODS:
      Forty patients with chronic obstructive pulmonary disease were divided into two
      groups randomly and were given 20 mg oral prednisolone once daily perioperatively
      (Group I, n = 20) or identical placebo (Group II, n = 20). FEV(1) values, dates
      of intensive care unit and hospital stays of the two groups were compared.
      RESULTS: FEV1 values during the admission to our hospital were similar in each
      group mean predicted FEV1: 56.7 +/- 5.35% in Group I and 57.2 +/- 4.88% in Group
      II (p = 0.759). After 10 days of oral prednisolone treatment in Group I,
      predicted FEV1 values were significantly different between two groups (63.2%+/-
      4.24 and 57.9%+/- 4.38) (p = 0.0001). While predicted FEV1 values revealed
      difference between two groups at the date of discharge (p = 0.0001) the values
      became similar at the third month (55.6%+/- 4.09 in Group I and 55.45%+/- 3.87 in
      Group II) (p = 0.897). CONCLUSION: Various types of complications may occur after
      cardiopulmonary bypass. Oral prednisolone not only decreases the rates of
      complications (reintubation, intubation times, and rhythm disturbances) but also
      decreases the cost of cardiac operations according to shorter hospital stays.

PMID- 15854088
TI  - Effect of posterior pericardiotomy on early and late pericardial effusion after
      valve replacement.
AB  - OBJECTIVE: Pericardial effusion (PE) after cardiac surgery is frequent. It is
      more frequently seen after valve replacement or other types of heart surgery.
      Oral anticoagulants and antiplatelet agents may induce effusion development after
      open heart surgery. Our objective was to determine the efficiency of posterior
      pericardiotomy (PP) after cardiac valve operation for reducing the incidence of
      early and late PE and tamponade. METHODS: This prospective randomized study was
      carried out in 100 consecutive patients undergoing mechanical valve replacement
      between August 2001 and May 2003 in our institution. Patients were divided into
      two groups; each group consisted of 50 patients. Longitudinal incision was made
      parallel and posterior to the left phrenic nerve, extending from the left
      inferior pulmonary vein to the diaphragm in Group 1. Posterior pericardiotomy was
      not done in Group 2. RESULTS: Early PE was detected in four patients (8%) and in
      19 patients (38%) in Group 1 and Group 2, respectively (p < 0.001). No late PE
      effusion was developed in Group 1 despite nine (18%) late PE developing in Group
      2 (p < 0.003). The rate of delayed pericardial tamponade was lower in Group 1,
      but this difference was not statistically significant (0% vs 10%; p < 0.056).
      CONCLUSION: These findings suggest that PP is an easy, feasible, and beneficial
      technique for reducing both the occurrence of early and late PE or pericardial
      tamponade in patients undergoing valve replacement.

PMID- 15854089
TI  - Repair of ALCAPA in a 4-kg patient followed by successful weaning and "off-pump"
      explantation of an apical venting pulsatile LVAD.
AB  - Even in infants and small children, ventricular assist devices have an emerging
      role in the treatment of congenital and postcardiotomy heart failure.
      Extracorporeal pneumatic pulsatile devices are considered the strategy of choice
      if long-lasting bridge to recovery or transplantation is expected. However,
      complete explantation of the device may be complicated by hemorrhage and
      subsequent transfusions due to the establishment of CPB. The present case
      demonstrates successful weaning and complete removal of an apical venting
      pulsatile LVAD in a 4-kg infant without the employment of CPB.

PMID- 15854090
TI  - Autopericardial patch tracheoplasty for tracheal stenosis after arterial switch
      operation.
AB  - Though congenital tracheal stenosis in infants with congenital heart disease is
      uncommon, congestive heart failure is often deteriorated by respiratory symptoms.
      We report an infant having a diagnosis of congenital tracheal stenosis
      complicated with congenital heart disease who underwent pericardial patch
      tracheoplasty after the arterial switch operation for the transposition of the
      great arteries. External appearance of the trachea showed no stenosis and
      tracheal rings were well formed. Intraoperative bronchofiberscopy
      transilluminated the upper border of stenosis. The trachea was opened
      longitudinally to the extent of 30 mm to the point from 10 mm point proximal to
      the bifurcation. The incision was enlarged with the autologous pericardial patch
      using running absorbable suture. Then pericardial patch was anchored at several
      points to the posterior surface of the ascending aorta, innominate artery, and to
      the strap muscles of the neck. He is doing well now without any respiratory
      symptom.

PMID- 15854091
TI  - Combined valve and coronary surgery in a patient with erythropoietic
      protoporphyria.
AB  - Erythropoietic protoporphyria (EPP) is an autosomal dominant disorder of heme
      synthesis, causing excess of protoporphyrin in blood, skin, liver, and other
      organs. A 58-year-old male patient with EPP underwent aortic valve replacement
      and a concomitant aortocoronary bypass. The patient has been followed without
      complications due to EPP postoperatively. Cardiac surgery can safely be performed
      on patients with EPP by considering close attention not to stimulate porphyrin
      synthesis.

PMID- 15854092
TI  - Reverse "U" aortotomy for aortic valve replacement after previous coronary artery
      bypass grafting.
AB  - The presence of patent vein grafts on the proximal aorta may give technical
      difficulties during exposure to aortic valve replacement after previous coronary
      artery bypass operations. A tongue or reverse "U" shape aortotomy allows
      excellent exposure of the aortic valve and antegrade cardioplegic administration
      without mobilizing vein grafts. This approach may facilitate uni- or
      bidirectional aortic root enlargement in patients with small aortic root.

PMID- 15854093
TI  - The reinforced sternal closure system is reliable to use in elderly patients.
AB  - BACKGROUND: Sternal dehiscence is a rare, but serious complication after cardiac
      surgery procedures when performed through mid-line sternotomy. Osteoporosis,
      especially at advanced age, may be a significant factor in the unfavorable
      results of sternum fixation. The present prospective, randomized study was
      carried out to evaluate whether the reinforced sternal-closure system is an
      effective and safe fixation and approximation of the sternum in cardiac
      procedures, and to compare with the conventional sternal-closure method in
      elderly patients. METHODS: Forty elderly patients underwent various cardiac
      procedures via mid-line sternotomy under cardiopulmonary bypass. Patients were
      randomized into two groups: group I (n = 20) closed with the reinforced sternal
      closure system, and group II (n = 20) with standard stainless steel wires. The
      mean age of patients in group I was 70.5 years, and group II with 70.4 years.
      RESULTS: Superficial wound infection appeared in only one case of stapler group
      and in two cases of control group. Deep wound infections or dehiscence was not
      detected in the patients of both groups. There were no significant differences in
      the patient's age, drainage, pain index, time of removal of the drains, and
      postoperative hospital stay between the groups (p > 0.05). CONCLUSIONS: The
      reinforced sternal-closure system provided no additional risk with similar
      postoperative pain index and postoperative hospital stay compared with
      conventional method. It is reliable to use in elderly patients undergoing open
      heart surgery, in the cases presenting a risk factor such as osteoporosis for
      increased incidence of sternal dehiscence.

PMID- 15854094
TI  - Repair of multiple muscular ventricular septal defects: septal obliteration
      technique.
AB  - BACKGROUND: The management of the apical multiple muscular ventricular septal
      defects (VSDs) remains still controversial. There are various surgical techniques
      and approaches for closure of "Swiss-cheese" VSDs. In this study, we report the
      outcome of multiple muscular VSDs repair, using the septal obliteration
      technique. METHODS: We used the septal obliteration technique in five "Swiss
      cheese" ventricular septal defects cases through right atriotomy. Four of the
      cases had isolated multiple VSDs. One case also had an aortic arch interruption
      type A, which was repaired prior to cardiopulmonary bypass. Their ages varied
      between 43 days and 6 years. RESULTS: We did not experience any mortality or
      serious morbidity. Tracheostomy was required in one patient. There was no
      important residual shunt in postoperative period, except a minimal shunt in one
      case. CONCLUSION: The closure technique of "Swiss-cheese" trabecular multiple
      VSDs using a large single patch was not troubling. Transatrial approach prevented
      postoperative problems of ventricular incision. Using a large needle with a large
      pledgett is the key, which provides deep tissue penetration to avoid residual
      shunt.

PMID- 15854095
TI  - Endocavitary patch repair for a left ventricular pseudoaneurysm: an alternative
      approach.
AB  - We present a case of postinfarction posterolateral left ventricular wall
      pseudoaneurysm with severe mitral regurgitation and poor left ventricular
      function. The patient had New York Heart Association (NYHA) class IV heart
      failure at the time of surgery, which was performed on an emergency basis. The
      surgical approach included coronary revascularization, surgical posterior mitral
      leaflet detachment with patch closure of the pseudoaneurysm neck from inside of
      the left ventricular cavity followed by mitral valve reconstruction, and
      subsequent implantation of a mitral annuloplasty ring.

PMID- 15854096
TI  - "Off-pump" repair of a postangioplasty coronary artery bleed.
AB  - Following percutaneous multivessel coronary stent implantation with full
      anticoagulation, a 65-year-old man suffered tamponade and cardiac arrest. After
      successful resuscitation, he underwent repeat coronary angiography which
      demonstrated extravasation of contrast from a distal circumflex subbranch.
      Thereafter, he was transferred to the cardiothoracic surgery unit where the
      leaking vessel was oversewn using the Medtronic Octopus Retractor for
      stabilization. This report illustrates the growing wider use of "off-pump"
      techniques beyond coronary artery bypass grafting. In this case, the patient was
      exposed to a much shorter procedure with less morbidity than could have been
      expected had cardiopulmonary bypass been used.

PMID- 15854097
TI  - Successful off-pump pericardiectomy and coronary artery bypass in liver
      cirrhosis.
AB  - Cardiopulmonary bypass can be detrimental to patients with hepatic cirrhosis.
      Pericardiectomy performed on the beating heart is an effective treatment for
      pericardial constriction. Off-pump coronary artery bypass grafting is becoming
      firmly established as a surgical option for myocardial ischemia associated with
      multivessel disease. A single-stage operation combining both procedures without
      utilizing cardiopulmonary bypass has not been reported. This provided excellent
      surgical outcome for a patient with the dual pathology and coexisting liver
      cirrhosis. The off-pump approach should be considered in such a high-risk
      scenario.

PMID- 15854098
TI  - Successful surgical correction of a single atrium associated with cleft mitral
      valve persistent left superior vena cava and pulmonary valvular stenosis as an
      isolated cardiac defect.
AB  - Single atrium (SA) is a complex cardiac anomaly and generally a component of
      certain congenital syndromes. It is extremely rare for SA to be observed as an
      isolated defect. We report here a 13-year-old male patient with SA as an isolated
      cardiac defect, successfully corrected by surgery.

PMID- 15854099
TI  - Critical role of inferior vena caval filter placement after pulmonary
      embolectomy.
AB  - Surgical pulmonary embolectomy is a definitive treatment for patients with severe
      pulmonary embolism (PE). Postoperative placement of an inferior vena caval filter
      (IVCF) may prevent recurrent PE. We present a patient who underwent pulmonary
      embolectomy in whom postoperative placement of an IVCF was postponed due to
      hemodynamic instability and severe hemorrhage. Recurrent PE was recognized 12
      hours after the initial surgery, and required reoperative pulmonary embolectomy.
      This report documents that recurrent PE can occur early after pulmonary
      embolectomy even in the presence of coagulopathy. Therefore, concurrent IVCF
      placement should be considered during or immediately after pulmonary embolectomy
      to prevent recurrent pulmonary embolism.

PMID- 15854100
TI  - Incidental locally infiltrating malignant thymoma and coronary artery bypass
      surgery-excision should always be considered.
AB  - The incidental finding of thymic tumors during thoracic surgery has been
      reported. Meticulous management planning is necessary if such tumor is found
      during a cardiac operation. We describe a rare case of asymptomatic invasive
      malignant thymoma discovered incidentally during routine elective coronary artery
      bypass grafting in a 48-year-old male. Total thymectomy and enbloc excision of
      tumor with adjacent involved pericardium, pleura, and phrenic nerve was
      performed. This was followed by quadruple coronary artery bypass grafting and
      adjuvant radiotherapy. The patient made an uneventful recovery and remains free
      from recurrence and angina 2 years following surgery. The different management
      options available for incidentally occurring malignant thymomas are discussed.

PMID- 15854101
TI  - Intravenous magnesium for prevention of atrial fibrillation after coronary artery
      bypass surgery: a systematic review and meta-analysis.
AB  - Atrial fibrillation (AF) is one of the most common complications after coronary
      artery bypass surgery. The objective of this study was to assess the
      effectiveness of intravenous magnesium in preventing postoperative atrial
      fibrillation. A meta-analysis of eight identified randomized controlled trials,
      reporting comparisons between magnesium and control was undertaken. The primary
      outcome was incidence of postoperative atrial fibrillation. Our review revealed
      that use of intravenous magnesium is associated with a significant reduction in
      the incidence of atrial fibrillation after coronary artery bypass surgery, with a
      relative risk of 0.64 (95% confidence interval = 0.47, 0.87, and p = 0.004).

PMID- 15854102
TI  - Surgical management of cardiac myxoma.
AB  - OBJECTIVE: Between 1994 and December 2003, 55 patients were operated for cardiac
      myxoma in Kosuyolu Heart and Research Hospital in Istanbul. METHODS: We
      retrospectively analyzed our results according to the preoperative
      characteristics, operative procedures, and postoperative courses. RESULTS: Of 55
      patients operated, 36 (65.4%) were female and 19 (34.6%) male. The average age of
      the patients was 48 +/- 15.5 years (range, 12-75). Thirteen patients (23.6%)
      previously had cerebrovascular accidents. Peripheral arterial emboli had occurred
      in 11 (20%) patients. The majority of the patients (44.4%) were in NYHA Class II
      preoperatively. One patient was presented with Carney's complex. Most frequent
      location was the left atrium (85.2%). Eight patients had concommitant surgery
      together with myxoma extirpation. Postoperative courses were uneventful. Three
      patients had a new onset atrial fibrillation, two had transient conduction
      disturbances. There were two (3.6%) in-hospital deaths. No recurrences have been
      noted during the 82.4 +/- 40.6 months (a total of 315.75 patient/years) follow
      up. CONCLUSIONS: Surgical management of cardiac myxoma gives excellent results.
      In selected cases, a conservative approach may be adequate. Despite the scarcity
      of the neoplastic properties, careful follow-up is necessary.

PMID- 15854104
TI  - A health policy paradox: the mind-body disconnect in primary mental healthcare
      policy. Part I.

PMID- 15854105
TI  - Heart failure from diastolic dysfunction related to hypertension: guidelines for
      management.
AB  - PURPOSE: To provide advanced practice nurses with a greater understanding of the
      pathophysiology, diagnostics, and management of diastolic dysfunction resulting
      from hypertension. DATA SOURCES: Electronic database searches were performed
      using Medline and CINAHL. Data were obtained from medical textbooks and research
      and review articles. CONCLUSIONS: As the number of older adults with heart
      failure (HF) continues to increase, so will the need for effective care and
      guidance. In addition to further testing of appropriate pharmacologic regimens,
      adherence factors such as medication costs and patients' functional abilities
      must be considered. IMPLICATIONS FOR PRACTICE: HF resulting from diastolic
      dysfunction has emerged as a separate entity over the past 10-15 years. One of
      the most common causes of diastolic dysfunction is uncontrolled hypertension.
      Populations at greatest risk include elders, particularly women, and African
      Americans.

PMID- 15854106
TI  - Telemedicine: benefits to advanced practice nursing and the communities they
      serve.
AB  - PURPOSE: To review the use of telemedicine in a variety of advanced nursing
      practice settings, its contribution in expanding the service and role of the
      nurse practitioner, and the regulatory issues of reimbursement and licensure.
      DATA SOURCES: Literature review of relevant journals, research articles, case
      examples, and web searches. CONCLUSIONS: Although telemedicine has been utilized
      for many years, it has historically been used primarily by physicians. In recent
      years, telemedicine has been demonstrating its growing potential in advanced
      nursing practice in terms of economy, efficacy, and quality of care. When used
      appropriately, telemedicine complements advanced nursing practice in cost
      effective ways and improves healthcare access to the populations served.
      IMPLICATIONS FOR PRACTICE: Incorporating telemedicine into the advanced nursing
      practice can be rewarding for both clinicians and their patients. Because of the
      high variability that exists among state regulations and payer reimbursements,
      clinicians are advised to verify their respective Board of Nursing Examiners,
      State, and payers' policies prior to investing in the establishment of
      telemedicine in practice.

PMID- 15854107
TI  - Coccidioidal meningitis presenting as memory loss.
AB  - PURPOSE: This case study is designed to help the nurse practitioner recognize
      atypical symptoms of coccidioidal meningitis, particularly in high-risk groups
      that require further diagnostic treatment. DATA SOURCES: Selected research,
      clinical articles, and case studies. CONCLUSIONS: Coccidioidal meningitis is a
      potentially lethal infection unless recognized and treated. Unlike other
      infectious meningitides that present with more acute meningeal symptoms,
      disseminated coccidioidomycosis can present insidiously. When it presents as
      cognitive dysfunction, it may be mistaken for early dementia and if undiagnosed
      can result in death. While it is an infectious disease that is endemic to a small
      number of southwestern states, these areas see a high volume of tourists who can
      unwittingly become infected. Knowledge of this infectious disease and the many
      ways it can imitate other diseases is critical to its early recognition and
      treatment. IMPLICATIONS FOR PRACTICE: Failure to recognize this reemerging,
      endemic fungal infection in high-risk groups can result in death.

PMID- 15854108
TI  - Fetal alcohol spectrum disorders prevention: an exploratory study of women's use
      of, attitudes toward, and knowledge about alcohol.
AB  - PURPOSE: The incidence of fetal alcohol spectrum disorders (FASD) is increasing,
      even though it is 100% preventable. This study examined use of, knowledge about,
      and attitudes toward alcohol of women requesting emergency contraception (EC)
      and/or a pregnancy test, and evaluated whether a brief intervention would be
      effective in educating them about the risks of FASD. DATA SOURCES: Fifty women
      from two outpatient clinics participated. Information was collected on
      demographic and personal health habits, alcohol use, and knowledge of and
      attitudes toward alcohol. As a brief intervention to increase knowledge about
      FASD, participants read a short pamphlet about the risks of alcohol exposure in
      pregnancy and then completed a post-test questionnaire. Descriptive statistics,
      including means, standard deviations, and skewness, were calculated for all
      variables. Pearson correlations were computed to assess relationships between
      demographic/lifestyle variables and attitudes toward and knowledge about alcohol.
      Paired t-tests were used to analyze the relationship between pretest and post
      test knowledge scores. CONCLUSIONS: The majority of participants were single
      (76%), college educated (94%), and received EC at the clinic visit (60%). The
      average age was 24 years. Slightly over half (52%) reported drinking beer at
      least once a week, with one to six cans on occasion. Younger women expressed more
      tolerant attitudes toward alcohol use (p= .02) and drank significantly more beer
      on occasion (p= .015). Women who reported drinking alcohol when they last had sex
      were significantly (p= .017) less tolerant in their attitudes toward alcohol use.
      The intervention used in this study was effective in communicating knowledge
      about FASD to this population (p < .0001). IMPLICATIONS FOR PRACTICE: These
      findings suggest that young women may be engaging in behaviors that could put
      potential offspring at risk for exposure to alcohol. Clinicians are advised to
      take a thorough history to determine alcohol use in all women of childbearing age
      and to provide information regarding FASD prevention.

PMID- 15854109
TI  - Healthcare providers' perspectives: estimating the impact of chronicity.
AB  - PURPOSE: To compare elders' self-ratings of the impact of their chronic
      conditions with healthcare providers' estimates of the impact of the same
      conditions on older adults. The effect of length of time in clinical practice and
      rural or urban clientele on healthcare providers' impact ratings was also
      explored. DATA SOURCES: A pen-and-paper survey was administered to 122 community
      dwelling adults aged 55 years and older, attending health education or exercise
      programs held by a hospital in a city of approximately 60,000 people. Elders were
      asked to identify which of 11 common chronic conditions they had and then to rate
      the impact each condition had on their daily lives. A sample of 290 healthcare
      providers who are members of the Gerontological Society of America completed a
      mailed survey asking them to estimate the impact that each of the 11 conditions
      had on older adults. CONCLUSIONS: Healthcare providers consistently overestimated
      the impact that chronic health conditions had on older adults when compared with
      the elders' self-ratings of impact. Greater levels of experience were not
      significantly related to providers' impact ratings of chronic conditions.
      IMPLICATIONS FOR PRACTICE: Nurse practitioners, as primary care providers, must
      understand the impact of chronic conditions on older adults' daily lives in order
      to provide effective, efficient, and evidence-based health care. This study
      points to the need for more research to discover why older adults and healthcare
      providers have such different perspectives on the impact of chronic health
      conditions.

PMID- 15854111
TI  - Danish dentists' knowledge, attitudes and management of procedural dental pain in
      children: association with demographic characteristics, structural factors,
      perceived stress during the administration of local analgesia and their tolerance
      towards pain.
AB  - OBJECTIVE: The aim of the present study was to describe Danish dentists'
      knowledge of, attitudes towards and management of procedural pain during
      paediatric dental care, and to assess the importance of demographic
      characteristics, structural factors, perceived stress during administration of
      local analgesia and the dentists' own tolerance towards procedural dental pain.
      DESIGN: A cross-sectional questionnaire study was conducted in Denmark in May
      2001. SUBJECTS AND METHODS: The subjects were a random sample of 30% of Danish
      dentists treating children. Usable information was obtained from 327 (80.3%) of
      the dentists in the sample. RESULTS: One-quarter of the respondents answered that
      a 3-5-year-old child could report pain only with uncertainty. More than 80% of
      the dentists stated that they never compromised on painlessness. Very few agreed
      to the statement that children forget pain faster than adults. One-third agreed
      to, or were neutral to, the statement that all restorative care in primary teeth
      could be performed painlessly using N2O-O2 sedation alone. The majority of the
      respondents reported using three or more methods to assess the effect of their
      pain control methods. Almost 90% reported using local analgesia for restorative
      work 'always' or 'often'. A similar proportion reported using topical analgesia
      before injection 'always' or 'often'. Administering a mandibular block to
      preschool children was the procedure perceived as the most stressful (33.6%) pain
      control method. Demographic factors (gender), structural factors (always working
      alone and treating 3-5-year-old children daily), perceived stress during the
      administration of a mandibular block in preschool children and the dentists' own
      willingness to accept potentially painful dental treatment without local
      analgesia were associated with knowledge of, attitudes towards and management of
      procedural dental pain in children. CONCLUSIONS: Danish dentists treating
      children demonstrate concern about procedural dental pain in children. Factors
      amenable to change via training and reorganization into larger clinical units
      seem to determine their knowledge of, attitudes towards and management of
      procedural dental pain in children.

PMID- 15854112
TI  - A study to assess the validity of clinical judgement in determining paediatric
      dental anxiety and related outcomes of management.
AB  - OBJECTIVE: The aim of the present study was to determine the validity of
      subjective anxiety assessment and the outcomes of management of children
      receiving operative dental treatment. SETTING: The study was conducted at the
      Departments of Sedation and Child Dental Health, Newcastle Dental Hospital,
      Newcastle upon Tyne, UK. SUBJECTS AND METHODS: One hundred children and
      adolescents aged between 8 and 15 years participated in the study. Clinicians
      subjectively allocated 50 children for treatment with local analgesia alone (low
      anxiety), and identified 50 children who had the potential to benefit from
      nitrous oxide and oxygen sedation (high anxiety). Participants then completed the
      State-Trait Anxiety Inventory for Children (STAIC), the Venham Picture Test (VPT)
      and the Child Fear Survey Schedule-Dental Subscale (CFSS-DS). A global rating
      scale classified behaviour during dental treatment. RESULTS: State anxiety and
      dental fear prior to treatment were significantly higher in children allocated to
      receive inhalation sedation (P = 0.004 and P = 0.005, respectively). There was no
      significant difference in trait anxiety or post-treatment state anxiety between
      the two groups (P = 0.69 and P = 0.06, respectively). Only 11% displayed
      'negative' behaviour during treatment: 82% of this group represented those
      allocated to receive sedation. CONCLUSION: Children receiving inhalation sedation
      were significantly more anxious prior to treatment than children receiving
      treatment with local analgesia alone. The findings support the subjective
      assessment of anxiety in children; however, objective anxiety measures may assist
      clinicians in identifying specific fears, which may ultimately aid patient
      management.

PMID- 15854113
TI  - Dental emergencies presenting to a university-based paediatric dentistry clinic
      in the West Indies.
AB  - OBJECTIVES: The aims of the present study were to investigate the type and
      prevalence of dental emergencies presenting at a teaching hospital paediatric
      emergency clinic in Trinidad, and to describe the socio-demographic factors
      related to the use of the service. DESIGN AND METHODS: The authors used a
      prospective study of consecutive dental patients presenting to a paediatric
      emergency clinic. Data recorded included type of presenting emergency and socio
      demographic variables. RESULTS: Data were available for 309 participants; 47%
      were male and 53% female. The average age of the participants was 8.66 years (SD
      = 3.75 years; range = 1-16 years). Seventy-three per cent of the participants'
      parents were involved in manual work or unemployed, and 21% were in
      nonmanual/professional employment; the occupation was not known in 6% of cases.
      Caries-related problems accounted for 74% of emergencies. Dental trauma mostly
      affected the upper permanent incisor teeth, with concussion, subluxation and
      intrusion being the most common injuries. CONCLUSION: Dental emergencies
      presenting to this university-based clinic were predominantly related to caries
      and trauma. The service was more frequently utilized by children in the mixed
      dentition stage, children from lower socioeconomic groups and those living in the
      local area. The frequency of caries-related problems indicates the need for more
      community-based preventive strategies, including encouraging greater attendance
      for routine dental care and dental health education. Strategies for oral health
      promotion should also be developed to prevent dental trauma.

PMID- 15854114
TI  - Prevalence of cleft lip and palate in a hospital-based population in the Sudan.
AB  - Cleft lip and palate represents one of the most common developmental deformities
      seen in oral surgery clinics. It is usually associated with problems which
      include not only cosmetic and dental abnormalities, but also speech, hearing and
      facial growth difficulties. OBJECTIVES: The purpose of the present study was to
      determine the prevalence of cleft lip and palate in births taking place in
      hospitals in the Sudan. METHODS: The records of 15,890 Sudanese new-borns
      delivered at three hospitals during the period from 1997 to 2000 were examined.
      RESULTS: Thirteen cases of cleft lip and palate were found, demonstrating a
      prevalence of 0.9 per 1000. There were more girls than boys, with a male:female
      ratio of 3:10. Fifty-four per cent of the cases had cleft lip with cleft palate,
      30% had only cleft palate and the remaining 16% had cleft lip alone. CONCLUSIONS:
      The present study was confined to hospital-based births in one city, and the true
      incidence of cleft lip and/or palate in the Sudan is not yet known. Findings
      differ from reports from other countries in terms of suggesting a higher
      incidence in girls.

PMID- 15854115
TI  - Eating habits, smoking and toothbrushing in relation to dental caries: a 3-year
      study in Swedish female teenagers.
AB  - OBJECTIVES: The aims of the present study were to describe eating, toothbrushing
      and smoking habits in a cohort of Swedish female adolescents, and to relate the
      findings to dental caries increment. DESIGN: The research took the form of a
      longitudinal study. SUBJECTS AND METHODS: The study sample consisted of a cohort
      of 162 girls under regular dental care, aged 12 years at baseline, who were
      followed for 3 years, from the sixth to the ninth grade. Eating, oral cleaning
      and smoking habits were self-reported three times per year through a
      questionnaire, and caries data at baseline and after 3 years were collected from
      dental records. RESULTS: The results showed significantly (P < 0.05) impaired
      eating habits during the study period and that adherence to regular main meals
      diminished. In the eighth grade, one-third of the girls skipped breakfast before
      school and only 50% had their free school lunch daily. The omission of breakfast
      and irregular main meals, as well as smoking were significantly associated with
      caries (decayed, missed and filled surfaces) increment in the eighth grade (odds
      ratio = 4.1-4.9, P < 0.05). Snacks, light meals, soft drinks and sweets were
      already frequently consumed at baseline and continued to be so over the years.
      Although > 95% of subjects reported that they brushed their teeth at least once a
      day, approximately 20% did not do it every evening, and this figure remained
      stable over the study period. However, snacks, soft drinks and sweets, and
      toothbrushing habits had no significant influence on caries development.
      CONCLUSION: Dietary advice for caries prevention in adolescent girls should focus
      on the importance of retaining regular main meals, and especially, not skipping
      breakfast.

PMID- 15854116
TI  - Primary care research: difficulties recruiting preschool children to clinical
      trials.
AB  - OBJECTIVES: The aims of the present study were to report difficulties experienced
      recruiting preschool children to a clinical trial and to report the acceptability
      of a dental intervention to their parents. DESIGN: The study was a randomized
      controlled trial (RCT). SETTING: The study took place in community dental
      clinics, health centres and patient homes. SAMPLE AND METHODS: Health visitors
      were used to recruit 508 children aged between 18 and 30 months from high caries
      areas of South Wales. Children with caries-free first primary molars were entered
      into a placebo-controlled individual RCT of fissure sealants. All children
      received a standard package of dental health education. Children in the test
      group had their first primary molars sealed with glass ionomer. All children were
      reviewed once. Families were asked to rate the acceptability of procedures.
      RESULTS: Health visitors referred 1228 children for screening, but only 547 were
      seen (44.5%) and 508 subjects were recruited to the trial. Of these, 449 (88.4%)
      were seen at follow-up. Some 667 children missed 1610 visits at baseline, and 373
      of those recruited missed an appointment. At follow-up, 1056 appointments were
      staffed to review 449 children. Three-quarters of parents reported the
      examination to be very easy. CONCLUSIONS: Preschool children are difficult to
      access for community trials. Dental examinations and sealant placement were
      acceptable to the majority of families who were seen.

PMID- 15854117
TI  - Acid-etched and erbium:yttrium aluminium garnet laser-treated enamel for fissure
      sealants: a comparison of microleakage.
AB  - OBJECTIVES: A pilot study aimed to compare the microleakage of pit and fissure
      sealants in acid-etched and Erbium:Yttrium Aluminium Garnet (Er:YAG)-treated
      enamel. METHODS: Forty permanent noncarious young molars and premolars, which
      were extracted for orthodontic reasons, were selected. The teeth were divided
      into four groups, with five molars and five premolars in each group. The groups
      were treated as follows: (1) group A--laser irradiation of the enamel of the
      occlusal surface without contact and in scanning mode was carried out using an
      Er:YAG laser, placement of sealant material, light curing, and thermocycling
      between 6 degrees and 55 degrees C; (2) group B--the same as group A, but with no
      thermocycling; (3) group C--acid etching of the enamel surface, placement of
      sealant material, light curing and thermocycling; and (4) group D--the same as
      group C, but with no thermocycling. After being immersed in 1% methylene blue
      solution, all teeth were sectioned in the mesio-distal dimension into four
      slices. Images of the slices were then scanned to a Macintosh G3 computer and
      examined for marginal leakage. Leakage was measured by the degree of dye
      penetration. Three independent examiners evaluated the dye penetration. RESULTS:
      No penetration of dye material was observed in any of the slices in any of the
      four groups by any of the examiners. CONCLUSIONS: No difference in microleakage
      was seen between lasing or acid etching, and therefore, the results of the
      present study would suggest that the technique may be efficacious.

PMID- 15854118
TI  - Maxillary premolar resorption by canines: three case reports.
AB  - Three unusual cases of maxillary premolar root resorption are reported. Three
      teenage patients were referred to the orthodontic department for management of
      ectopic maxillary canines. Radiographic examination revealed unilateral premolar
      root resorption in all three patients. This represents an unusual finding.
      Whereas the prevalence of maxillary lateral incisor root resorption secondary to
      palatally ectopic canines has been reported, the prevalence of premolar root
      resorption is unknown. This report discusses the findings in the context of the
      available literature. The postulated aetiology and the need for early diagnosis
      are highlighted.

PMID- 15854119
TI  - Meningococcal septicaemia and dental complications: a literature review and two
      case reports.
AB  - The present report describes two cases of dental complications of meningococcemia
      at an early age. The meningococcal infection in these young children resulted in
      limb amputation and significant plastic surgery. Dental treatment and
      psychological considerations are described in both cases. Similar dental
      complications, especially in the premaxilla, were found. Some of the severely
      affected teeth were extracted.

PMID- 15854120
TI  - Kartagener's syndrome: unusual dental morphology.
AB  - The present paper describes the dental presentation of a female patient with
      Kartagener's syndrome. There are no reports in the literature identifying dental
      anomalies in patients with this condition. The subject presented with the
      congenital absence of an upper lateral incisor, enamel hypoplasia and aberrant
      tooth morphology.

PMID- 15854121
TI  - Peutz-Jeghers syndrome in a 14-year-old boy: case report and review of the
      literature.
AB  - Peutz-Jeghers syndrome (PSJ) is a relatively rare but well-recognized condition,
      with a prevalence of approximately one in 120,000 births in the USA. It is
      generally inherited as an autosomal dominant trait, although 35% of cases are new
      mutations. This disorder is characterized by melanocytic macules on the hands,
      feet, peri-oral skin and oral mucosa, and multiple gastrointestinal hamartomatous
      polyps. People with PSJ have an increased risk for developing a variety of
      malignant tumours. The aim of the present study was to report one case of PSJ in
      a 14-year-old boy with mucocutaneous pigmentation associated with duodenal
      hamartomatous polyps.

PMID- 15854125
TI  - Influence of prostaglandin F2alpha and its analogues on hair regrowth and
      follicular melanogenesis in a murine model.
AB  - Latanoprost and isopropyl unoprostone, which are analogues of prostaglandin
      F2alpha (PGF2alpha), are promising drugs for the reduction of intra-ocular
      pressure. However, they have been reported to have side effects, including
      hypertrichosis and hyperpigmentation of the eyelashes and periocular skin, and
      occasionally poliosis. In order to investigate these effects further, PGF2alpha,
      latanoprost and isopropyl unoprostone were applied to the dorsal skin of 7-week
      old C57BL/6 mice, and hair length was measured during the treatment. The three
      molecules all showed stimulatory effects on the murine hair follicles and the
      follicular melanocytes in both the telogen and anagen stages, and stimulated
      conversion from the telogen to the anagen phase. PGE2 is known to act
      synergistically with PGF2alpha, and hence the influence of PGE2 was also
      examined. PGE2 did not induce distinct telogen-to-anagen conversion, but showed
      moderate growth stimulatory effects on early anagen hair follicles. In addition,
      we observed a case of hypertrichosis and trichomegaly with an excess of
      melanogenesis, leading to the emergence of white hair, suggesting that poliosis
      can occur as a side effect of eye treatment with solutions of PGF2alpha
      analogues. The stimulatory effects of PGF2alpha and PGE2 on hair growth have been
      discussed with regard to the role of protein kinase C and mast cells.

PMID- 15854126
TI  - Quantitative analysis of laminin 5 gene expression in human keratinocytes.
AB  - To examine the expression of laminin 5 genes (LAMA3, LAMB3, and LAMC2) encoding
      the three polypeptide chains alpha3, beta3, and gamma2, respectively, in human
      keratinocytes, we developed novel quantitative polymerase chain reaction (PCR)
      methods utilizing Thermus aquaticus DNA polymerase, specific primers, and
      fluorescein-labeled probes with the ABI PRISM 7700 sequence detector system. Gene
      expression levels of LAMA3, LAMB3, and LAMC2 and glyceraldehyde-3-phosphate
      dehydrogenase were quantitated reproducibly and sensitively in the range from 1 x
      10(2) to 1 x 10(8) gene copies. Basal gene expression level of LAMB3 was about
      one-tenth of that of LAMA3 or LAMC2 in human keratinocytes, although there was no
      clear difference among immunoprecipitated protein levels of alpha3, beta3, and
      gamma2 synthesized in radio-labeled keratinocytes. Human serum augmented gene
      expressions of LAMA3, LAMB3, and LAMC2 in human keratinocytes to almost the same
      extent, and this was associated with an increase of the laminin 5 protein content
      measured by a specific sandwich enzyme-linked immunosorbent assay. These results
      demonstrate that the absolute mRNA levels generated from the laminin 5 genes do
      not determine the translated protein levels of the laminin 5 chains in
      keratinocytes, and indicate that the expression of the laminin 5 genes may be
      controlled by common regulation mechanisms.

PMID- 15854127
TI  - Downregulation of NDUFA1 and other oxidative phosphorylation-related genes is a
      consistent feature of basal cell carcinoma.
AB  - Basal cell carcinoma (BCC) is the most common cutaneous malignancy that, like
      other tumours, possesses a heterogeneous genetic composition. In order to select
      genes with consistent changes in expression among these tumours, we analysed BCC
      microarray expression data by using a novel approach, termed correlative analysis
      of microarrays (CAM). CAM is a nested, non-parametric method designed to
      qualitatively select candidates based on their individual, similar effects upon
      an array-wide closeness measure. We applied the CAM method to expression data
      generated by two-channel cDNA microarray experiments, where 21 BCC and patient
      matched normal skin specimens were examined. Fifteen candidate genes were
      selected, with six overexpressed and nine underexpressed in BCC vs. normal skin.
      Five of the nine consistently downregulated genes in the tumour samples are
      involved in mitochondrial function and the oxidative phosphorylation (OXPHOS)
      pathway. One of these genes was the 7.5-kDa subunit, NADH dehydrogenase
      (ubiquinone) alpha subcomplex-1 (NDUFA1), an accessory component of OXPHOS
      complex-I that is essential for respiratory activity. These findings support the
      hypothesis that irregularities in mitochondrial function are involved in
      neoplasia. Suppression of NDUFA1 expression could represent a key pathogenic
      mechanism in the development of BCC.

PMID- 15854128
TI  - UV-induced DNA damage in human keratinocytes: quantitation and correlation with
      long-term survival.
AB  - Ultraviolet (UV) radiation has a major role in the pathogenesis of skin cancer
      due to its capacity to induce immunosuppression and DNA damage in cells. In this
      study, we describe the use of a novel extra-long polymerase chain reaction (XL
      PCR) assay for detection of UV-inducible DNA lesions in a human keratinocyte line
      (HaCaT cells). Ultraviolet B (UVB), in doses from 4 to 50 mJ/cm2 resulted in a
      linear increase in the number of DNA lesions in the genome [range 0.3 +/- 0.2
      lesions-3.6 +/- 0.7 lesions (mean +/- SD)/10 kb]. At lower doses of UVB (<10
      mJ/cm2), 89 +/- 13% lesions were repaired within 24 h of culture. At higher
      doses, more lesions remained unrepaired, but the repair efficacy expressed as a
      proportion of repaired lesions to the total amount of DNA lesions remained
      constant in the range 0-50 mJ/cm2. Moreover, we demonstrated a correlation
      between the dose of UV and cell survival. The D37 (dose that reduced clonogenic
      survival to 37%) of UVB equaled 19 mJ/cm2, corresponding to the introduction of
      1.4 lesions/10 kb. In contrast to UVB, UVA1 irradiation neither induced
      measurable DNA damage nor induced cell death in the doses up to 15 J/cm2. In
      conclusion, the non-radioactive extra-long (XL)-based real-time (RT)-PCR assay
      system can be used to quantify the UV-induced DNA damage in intact cells. The DNA
      lesions detected by this assay are mainly induced by short-waved radiation in the
      UVB range, and unrepaired DNA lesions cause keratinocyte death or permanent cell
      cycle block.

PMID- 15854129
TI  - Involvement of urokinase-type plasminogen activator in
      sphingosylphosphorylcholine-induced angiogenesis.
AB  - Sphingosylphosphorylcholine (SPC) has been shown to accelerate wound healing. As
      angiogenesis is fundamental to proper wound healing, we examined the effect of
      SPC on angiogenesis using a well-established rat aortic ring assay. SPC
      significantly stimulated the sprouting of endothelial cells from rat aortic ring.
      Recognizing its potential effect on angiogenesis, we further investigated the
      action of SPC using human umbilical vein endothelial cells (HUVECs) cultured in
      vitro. SPC significantly accelerated the closure of in vitro wound. In addition,
      SPC markedly enhanced the chemotactic migration and capillary-like tube
      formation. Subsequently, we examined whether SPC affected the production of
      urokinase-type plasminogen activator (uPA), an important regulator of
      angiogenesis, and found that SPC stimulated the expression of uPA at both the
      transcriptional and translational levels. Consistent with these results, SPC
      increased the activity of cell-surface-associated plasminogen activator.
      Pretreatment with antiuPA antibody significantly diminished both the chemotactic
      migration and capillary-like tube formation, indicating the potential importance
      of uPA in SPC-induced angiogenesis. Together, these results suggest that SPC may
      affect angiogenesis in the wound-healing process via regulation of uPA
      production.

PMID- 15854130
TI  - Dopa oxidase activity in the hair, skin and ocular melanocytes is increased in
      the presence of stressed fibroblasts.
AB  - We previously reported that mesenchymal cells (dermal fibroblasts and dermal
      papilla cells) can stimulate dopa oxidase activity in the skin melanocytes. This
      study extends the investigation of the influence of the fibroblast in a
      comparative study of melanogenesis in melanocytes from the hair, the skin and the
      eye. Culture of melanocytes with normal proliferative dermal fibroblasts slightly
      increased dopa oxidase activity of the hair, skin and ocular melanocytes (by 17,
      11 and 28%, respectively), but co-culture with fibroblasts recovering from
      storage in liquid nitrogen or growth-arrested by means of gamma radiation showed
      much greater effects. Most dramatic results were obtained with fibroblasts, which
      had been both gamma-irradiated and then frozen in liquid nitrogen, where
      increases in dopa oxidase activity of 125, 227 and 185% for melanocytes of the
      hair, the skin and the eye, respectively, were seen. Experiments by using
      transwell cultures of melanocytes and fibroblasts and by using fibroblast
      conditioned medium showed that a large proportion of this fibroblast influence
      could be mediated by diffusible factors, of which a good proportion was
      attributable to basic Fibroblast Growth Factor (bFGF). The addition of bFGF
      significantly increased dopa oxidase activity of the skin melanocytes, when
      fibroblasts were present, but not in their absence. These data show that
      fibroblasts in vitro, particularly when deliberately stressed, have the ability
      to increase dopa oxidase activity in melanocytes of the hair, the skin and the
      eye and further suggest that this effect is mediated by bFGF acting in
      combination with some other fibroblast-derived factors.

PMID- 15854131
TI  - Two mouse mutations mapped to chromosome 11 with differing morphologies but
      similar progressive inflammatory alopecia.
AB  - Alopecia is a common dermatological condition in humans and other mammals. Here,
      we present two similar but histologically distinct mouse models of scarring
      alopecia. Both mutant lines were generated using random genome-wide N-ethyl-N
      nitrosourea mutagenesis, and both harbor dominant mutations on chromosome 11. In
      both mutants, there is an early onset of alopecia that progresses to nearly
      complete pelage hair loss in both males and females by 20 weeks of age.
      Histologically, there is an increased dermal cellularity due to inflammatory cell
      infiltration at 7-10 days of age. By 3 weeks of age, the epidermis is acanthotic
      and the dermis is approximately twice as thick as in control mice due to a
      substantial, mostly mononuclear, inflammatory cell infiltrate. This infiltrate
      becomes more perifollicular by 4-5 weeks of age but is localized differently in
      the two mutants. In alopecia 1 (Alo-1), the perifollicular infiltrate is confined
      to the portion of the follicle within the dermis, whereas in Alo-2, the
      infiltrate extends the full length of the follicle. Expression of major
      histocompatibility complex (MHC) class I on the follicular epithelium in the two
      mutants is much greater than that in non-mutants. Furthermore, MHC class I
      expression is localized differently in the two mutant lines and mirrors the
      pattern of the inflammatory infiltrate. Despite these differences, the clinical
      progression of alopecia is identical in both mutants. The early onset of the
      disease, predictable progression, and differences in inflammatory cell
      localization between the two mutants make these mice particularly useful models
      for inflammatory hair loss and autoimmune diseases in general.

PMID- 15854132
TI  - Apoptosis in CD30-positive lymphoproliferative disorders of the skin.
AB  - The spectrum of CD30-positive cutaneous lymphoproliferative disorders (CD30+
      CLPD) includes lymphomatoid papulosis (LyP), primary cutaneous CD30+ large T-cell
      lymphoma (LTCL) and rare borderline patients. Despite their malignant
      histopathology, CD30+ CLPD exhibit a low-grade malignant course with an excellent
      prognosis and a characteristic tendency for spontaneous regression. Apoptosis of
      tumour cells is considered a principal mechanism of tumour regression. We
      examined the proliferation and apoptosis rates as well as the expression of
      apoptosis-related proteins in various clinical entities, tumour cell lines and
      evolutional (evolving and regressing) stages of CD30+ CLPD. Skin biopsies of LyP
      (n = 20) and LTCL (n = 19) and five CD30+ lymphoma cell lines were analysed by
      means of immunohistochemistry and Western blotting in order to evaluate the
      proliferation (Ki67), apoptosis (FragEl) and expression of Bax, Bcl-x, C-kit and
      Mcl-1. A significantly higher apoptotic index (AI) was found in LyP (AI = 12.5%)
      than in LTCL (AI = 3.1%, P < 0.005). Bax was expressed by the majority of tumour
      cells in all forms of CD30+ CLPD and CD30+ cell lines. However, no Bax expression
      was found in tumour cell lines derived from systemic CD30+ lymphomas, which lack
      spontaneous regression and display an aggressive clinical course. No significant
      correlation was found between the expression of apoptosis-related proteins and
      the tumour type and evolutional stage of CD30+ CLPD. We conclude that the higher
      AI in LyP may contribute to the regression of LyP lesions and the excellent
      prognosis of the disease. Pro-apoptotic protein Bax is expressed at high levels
      in CD30+ CLPD and may play a crucial role in mediating apoptosis of tumour cells.

PMID- 15854133
TI  - Modeling TEWL-desorption curves: a new practical approach for the quantitative in
      vivo assessment of skin barrier.
AB  - The objective of the present study was to test the discriminative capacity of the
      mathematical modeling of the transepidermal water loss (TEWL) curves that result
      from a plastic occlusion stress test (POST) to variations in the skin barrier-
      insults inflicted to the skin or differences in two distinct anatomical regions.
      This study was exclusively performed in the arm. On the first part of the work,
      three different insults to the skin barrier were assessed: tape stripping, lipid
      extraction with ether : acetone, and skin-surface biopsy. Anatomical differences
      were studied in the mid-forearm and in the wrist. All sites were submitted to a
      POST, after which the desorption curves were recorded. The mathematical model was
      adjusted to the TEWL data points. Results indicate differences in the parameters
      obtained in the control and treated sites, which suggests differences in the
      water dynamics after the damage was inflicted and shows that the method is valid
      for the objectives proposed. There were also significant differences in the
      parameters obtained in the wrist and in the volar forearm, which indicates that
      the method is also sensitive to variations in skin histology and anatomy.

PMID- 15854134
TI  - In vitro culture of skin-homing T lymphocytes from inflammatory skin diseases.
AB  - We, in this study, describe how T lymphocytes in a skin biopsy can proliferate in
      vitro for up to 3 months by using T-cell growth factors - interleukin-2 (IL-2)
      and IL-4 yielding approximately 100-160 million T lymphocytes within 1 month. We
      established cell lines from three tuberculin skin tests, four positive patch
      tests, 15 of 16 biopsies from atopic dermatitis (AD), 15 of 19 biopsies from
      mycosis fungoides (MF), 12 of 24 biopsies from psoriasis vulgaris, which was
      significantly less than AD (P < 0.05), and with a reduced cumulative number of
      lymphocytes (P < 0.05). Omitting IL-2 and IL-4 led to immediate halt of
      proliferation. Blood mononuclear cells from patients and biopsies from healthy
      persons never gave cell lines. All cells were T lymphocytes expressing CD45RO+,
      HLA-DR+ and CD150. The CD7 expression was significantly increased in cell lines
      from AD (P < 0.05). T-cell receptor beta-chain studies by using reverse
      transcription-polymerase chain reaction showed that all T lymphocytes had access
      to the skin compartment. Single-stranded conformational analysis showed clonally
      expanded T cells numbering between 40 and 60 clones. After approximately 2 months
      of growth, the mean CD4+ : CD8+ ratio was for AD 1.20, MF 0.65 and psoriasis
      0.85. Patients with AD treated with cyclosporin-A had almost no growth of CD8+
      cells in vitro. Our findings indicate a changed homeostasis among skin-homing
      lymphocytes for in vitro culture. Our culture system of skin-homing T lymphocytes
      leads to a prominent cellular expansion allowing for a range of studies of in
      vivo activated skin T lymphocytes.

PMID- 15854138
TI  - Clarifying homologies in the mammalian cerebral cortex: the case of the third
      visual area (V3).
AB  - 1. Experiments in mammalian models are the main source of information on the
      neural architecture underlying human visual perception, establishing scientific
      boundaries for the interpretation of experiments using non-invasive techniques in
      humans and for the realistic modelling of visual processes. Thus, it is important
      to define the homology between visual areas in different species. 2. To date,
      relatively few visual areas can be defined with certainty across mammalian
      Orders. Here, we review the evidence pointing to the fact that the third visual
      area (V3; or area 19) is a crucial node of a system involved in shape recognition
      that exists in most, if not all, eutherian mammals. 3. The size and shape of area
      V3 are variable, even between species that belong to the same Order. Although
      some features of the visuotopic organization of V3 are constant (including the
      relative location of the representations of the upper and lower quadrant and
      correspondence between the anterior border and the representation of the vertical
      meridian of the visual field), others are variable between species and even
      individuals. A complex pattern of representation, involving topological
      discontinuities, can exist. 4. In addition to its location in relation to the
      first (V1) and second (V2) visual areas, the identification of V3 homologues can
      be aided by certain other features, including low myelination, weak cytochrome
      oxidase reactivity, response properties that are indicative in the processing of
      stimulus shape, relationship to clusters of neurons forming interhemispheric
      connections and projections from the koniocellular (W-cell-like) components of
      the lateral geniculate nucleus. 5. Recent research in primates has clarified the
      organization of the V3 homologue in members of this Order. Regions of cortex that
      were formerly thought to belong to V3 (including a densely myelinated region near
      the dorsal midline) are better considered as part of a separate dorsomedial area,
      involved in motion analysis and visuomotor integration. The redefined V3, which
      includes the 'ventral posterior area' and parts of the dorsolateral complex
      proposed by earlier studies, is very similar to V3 (area 19) of other species in
      terms of structure and function.

PMID- 15854139
TI  - Pretreatment with intravenous ascorbic acid preserves endothelial function during
      acute hyperglycaemia (R1).
AB  - 1. Acute hyperglycaemia may impair endothelial function. Ascorbic acid (AA),
      administered intra-arterially, has been reported to improve endothelium-dependent
      vasodilatation during a forearm hyperglycaemic clamp. Using a randomized, double
      blind, placebo-controlled, cross-over study, we investigated the potential for
      intravenous ascorbic acid to modify the endothelial response to acute systemic
      hyperglycaemia in humans. 2. Nine healthy male volunteers were recruited from the
      hospital staff. Endothelial function was determined by measuring the forearm
      blood flow responses to intrabrachial infusions of endothelium-dependent (ED) and
      endothelium-independent (EID) vasodilators. The endothelial function index (EFI)
      was derived from the ratio of ED and EID vasodilatation. Haemodynamic and
      endothelial function measurements were performed at baseline and then repeated 2
      h after a systemic hyperglycaemic clamp (14 mmol/L). The subjects, studied on two
      separate occasions, were randomized to placebo or 2 g intravenous ascorbic acid
      prior to the initiation of hyperglycaemia. 3. After systemic hyperglycaemia with
      placebo pretreatment, the EFI fell from 1.08 +/- 0.21 to 0.74 +/- 0.13
      (difference (95% confidence interval): 0.34 (0.20, 0.47); P < 0.001). When
      subjects were pretreated with ascorbic acid, the EFI was not affected by
      hyperglycaemia (1.11 +/- 0.21 to 1.12 +/- 0.17; P = 0.938). This difference
      between placebo and ascorbic acid was significant (P < 0.001). Plasma ascorbate
      concentrations decreased during hyperglycaemia and correlated directly with the
      reduction in the EFI (r = 0.798; P < 0.001). 4. Pretreatment with an intravenous
      bolus of ascorbic acid can prevent endothelial dysfunction during acute systemic
      hyperglycaemia. Therefore, ascorbic acid may have potential therapeutic use in
      clinical situations where acute hyperglycaemia may be a complication.

PMID- 15854140
TI  - Euphorbia thymifolia suppresses herpes simplex virus-2 infection by directly
      inactivating virus infectivity.
AB  - 1. The ethyl acetate (EtOAc) extract and 3-O-galloyl-4,6-(S)-hexahydroxydiphenoyl
      d-glucose (3OG46HG) of Euphorbia thymifolia Linnea have been shown to exhibit
      anti-herpes simplex virus (HSV)-2 activity in vitro. In the present study, we
      investigated the mode of action of these two compounds in suppressing HSV-2
      multiplication. 2. The results demonstrated that the EtOAc extract and 3OG46HG
      affected virus infectivity in a dose-dependent manner. The EtOAc extract
      significantly reduced virus infectivity at a concentration of 4.0 microg/mL,
      whereas 3OG46HG obviously diminished virus infectivity at concentration of a 0.5
      microg/mL. The virucidal ability of the EtOAc extract was affected by the
      incubation period, but not by the incubation temperature. In the case of the
      action of 3OG46HG against HSV-2, the effects of incubation time and temperature
      were negligible. 3. In summary, the EtOAc extract and 3OG46HG of E. thymifolia
      are concluded to inhibit HSV-2 multiplication by reducing virus infectivity.

PMID- 15854141
TI  - 15-F-isoprostane and 5-F-isoprostane are not triggers of myocardial
      preconditioning.
AB  - 1. Myocardial ischaemia-reperfusion in humans is associated with increased
      formation of 15-F(2t)-isoprostane and 5-F(2t)-isoprostane (15-F(2t)-IsoP and 5
      F(2t)-IsoP, respectively). Whether this formation is relevant clinically remains
      controversial. The present study was performed in order to evaluate the ability
      of the isoprostanes 15-F(2t)-IsoP and 5-F(2t)-IsoP to reduce myocardial ischaemic
      injury in rat isolated heart. 2. Rats were divided into six groups. Hearts were
      excised, perfused retrogradely and pretreated with vehicle (ethanol 5.10(-7) and
      2.10(-9) mol/L; n = 6), subjected to ischaemic preconditioning (n = 8) or
      pretreated with the isoprostanes 15-F(2t)-IsoP (3.10(-10) and 3.10(-7) mol/L; n =
      8) or 5-F(2t)-IsoP (10(-9) mol/L; n = 8). After a 5 min treatment-5 min washout
      period, hearts were submitted to 30 min global ischaemia, followed by a 120 min
      reperfusion period. 3. The infarct-to-ventricle zone ratio was significantly
      reduced in ischaemic preconditioned (20.6 +/- 2.6%) compared with vehicle groups
      (44.5 +/- 4.3 and 51.3 +/- 2.5% in groups pretreated with 5.10(-7) or 2.10(-9)
      mol/L ethanol, respectively). Pretreatment with either isoprostane had no
      cardioprotective effect; the infarct-to-ventricle ratios were 43.1 +/- 2.2, 49.4
      +/- 5.9 and 44.5 +/- 5.0% for groups treated with 3.10(-10) mol/L 15-F(2t)-IsoP,
      3.10(-7) mol/L 15-F(2t)-IsoP or 10(-9) mol/L 5-F(2t)-IsoP, respectively. 4. These
      data provide evidence that the isoprostanes 15-F(2t)-IsoP and 5-F(2t)-IsoP are
      not implicated in early myocardial preconditioning at concentrations similar to
      those found in the human coronary sinus following coronary angioplasty.

PMID- 15854143
TI  - Brain pharmacokinetics of lignocaine before and following intravenous
      perfluorocarbon emulsion infusion in sheep.
AB  - 1. Perfluorocarbon emulsions have potential medical applications, particularly as
      temporary oxygen carriers and are likely to be coadministered with other
      intravenous drugs. It is possible that perfluorocarbon emulsions may alter the
      disposition of other drugs in the body. 2. In the present study, we examined the
      brain pharmacokinetics of a 5 min infusion of 100 mg lignocaine in three
      chronically instrumented sheep before and after the administration of a new
      investigational perflurocarbon emulsion (Oxygent; Alliance Pharmaceutical, San
      Diego, CA, USA). 3. The rate constant for the blood : brain equilibration of
      lignocaine was larger after perflubron administration. This change could not be
      attributed to a change in brain blood flow and, therefore, may be the result of a
      change in the free fraction of lignocaine in the blood.

PMID- 15854142
TI  - Mutated G-protein-coupled receptor GPR10 is responsible for the
      hyperphagia/dyslipidaemia/obesity locus of Dmo1 in the OLETF rat.
AB  - 1. We have confirmed the Diabetes Mellitus OLETF type I (Dmo1) effect on
      hyperphagia, dyslipidaemia and obesity in the Otsuka Long-Evans Tokushima Fatty
      (OLETF) strain. The critical interval was narrowed down to 570 kb between
      D1Got258 to p162CA1 by segregation analyses using congenic lines. 2. Within the
      critical 570 kb region of the Dmo1 locus, we identified the G-protein-coupled
      receptor gene GPR10 as the causative gene mutated in the OLETF strain. The ATG
      translation initiation codon of GPR10 is changed into ATA in this strain and, so,
      is unavailable for the initiation of translation. 3. The GPR10 protein has a
      cognate ligand, namely prolactin-releasing peptide (PrRP). Centrally administered
      PrRP suppressed the food intake of congenic rats that have a Brown Norway derived
      Dmo1 region (i.e. with wild-type GPR10), but did not suppress that of the OLETF
      strain, indicating that GPR10 is without function and could explain hyperphagia
      in the OLETF strain. 4. Moreover, when restricted in food volume to the same
      level consumed by the congenic strain, OLETF rats showed few differences in the
      parameters of dyslipidaemia and obesity compared with congenic strains. 5. Taken
      together, these results demonstrate that the mutated GPR10 receptor is
      responsible for the hyperphagia leading to obesity and dyslipidaemia in the obese
      diabetic strain rat.

PMID- 15854144
TI  - Neural, hormonal and renal interactions in long-term blood pressure control.
      Proceedings of a conference, 7-10 December 2004, Jaipur, India.

PMID- 15854145
TI  - Hypertension 2020: confronting tomorrow's problem today.
AB  - 1. In developed countries, the major burden of disease is due to chronic
      diseases, such as heart disease and stroke. In contrast, the major burden of
      disease among people in developing countries has been due largely to diseases
      caused by malnutrition, poor sanitation and infection. In recent years, with
      increasing economic and demographic development, there has been a shift in
      developing countries from diseases caused by poverty towards chronic, non
      communicable, lifestyle-related diseases. The rapid emergence of these chronic
      diseases has not occurred with a similarly rapid decline in infectious diseases.
      Therefore, these developing countries are experiencing high rates of both
      infectious and chronic diseases. 2. The increase in chronic diseases in
      developing countries has been brought about by the increasing prevalence of risk
      factors, such as increased alcohol consumption, smoking, obesity, physical
      inactivity and low fruit and vegetable intake. In parallel with this, there is
      also increased evidence of high blood pressure and high cholesterol levels. 3.
      The preventive strategies required to reverse this trend for these emerging
      diseases include the education of public health professionals, the introduction
      of surveillance activities to monitor changes in risk factors, the introduction
      of health promotion, the development of prevention research and improved advocacy
      for disease prevention programmes. Experience from other countries provides
      evidence that prevention programmes can work. The global challenge is to ensure
      that implementation of such programmes in the world's developing nations does not
      come too late.

PMID- 15854146
TI  - Hypothesis: the systemic circulation as a regulated free-market economy. A new
      approach for understanding the long-term control of blood pressure.
AB  - 1. The purpose of the present paper is to discuss the long-term regulation of
      arterial blood pressure. Current thinking on the topic favours the theory that
      tight regulation is achieved through the action of a central (or primary)
      controller, usually assumed to be in either the brain or kidneys. 2. Here, an
      alternative explanation is considered; namely, that the average long-term level
      of arterial pressure is an emergent property of a decentralized control system.
      The goal of the system is to deliver nutrient-rich blood to distinct vascular
      regions based on their energy demand. 3. Specifically, the circulation is
      conceptualized as a free-market economy where tissues 'compete' for a scarce
      resource (the energy contained in blood) supplied by the heart-lung unit; the
      'price' of the resource (analogous to the reciprocal of arterial pressure) is
      determined primarily by the dynamic relationship between supply and demand, not
      by a central mechanism. 4. Based on this concept of the circulation as an energy
      market, economic analogies are used to suggest novel mechanisms by which the
      brain and kidney may affect the long-term control of blood pressure. 5. Market
      based control, a process derived from quantitative theoretical analysis of the
      performance of economic markets, is proposed as a new, potentially useful
      strategy for mathematically modelling the behaviour of the circulation.

PMID- 15854147
TI  - Hypothesis: set-points and long-term control of arterial pressure. A theoretical
      argument for a long-term arterial pressure control system in the brain rather
      than the kidney.
AB  - 1. It has been hypothesised that the 'set-point' for the long-term control of
      mean arterial (MAP) resides within the kidney. In this model, the set-point of
      the 'chronic renal function curve' establishes the steady state relationship
      between renal perfusion pressure and urinary excretion of sodium and water,
      which, in turn, affects blood volume and cardiac output. The 'renal-MAP set
      point' theory predicts that the kidney controls MAP to maintain its own excretory
      function and that long-term regulation of blood volume and cardiac output are
      paramount to the regulation of arterial pressure. 2. An alternative hypothesis is
      proposed in which the 'set-point' for the long-term control of MAP resides within
      the central nervous system (CNS) rather than the kidney. In contrast with the
      'renal-MAP set-point' model, the 'CNS-MAP set-point' model dictates that the
      brain controls MAP to maintain cerebral blood flow and CNS function. 3. The 'CNS
      MAP set-point hypothesis' predicts that long-term regulation of MAP is paramount
      to the regulation of blood volume and cardiac output. It is proposed that the
      'CNS-MAP set-point' system operates independently of the arterial baroreceptor
      reflex, which is a short-term controller of MAP. 4. The precise mechanisms by
      which the CNS 'senses' MAP are complex and remain to be discovered. The MAP
      'sensor' likely involves integration of hormone levels linked to body fluid
      homeostasis and osmoreceptor and baroreceptor inputs. It is also proposed that an
      as yet undiscovered 'central baroreceptor' exists within the brain itself. 5. The
      'CNS-MAP set-point hypothesis' predicts that many forms of experimental and
      essential hypertension are due to a primary shift in the CNS-MAP set-point.

PMID- 15854148
TI  - The 'body fluid pressure control system' relies on the Renin-Angiotensin
      aldosterone system: balance studies in freely moving dogs.
AB  - 1. The physiological role of the 'renal body fluid pressure control system',
      including the intrarenal mechanism of 'pressure natriuresis', is uncertain. 2.
      Balance studies in freely moving dogs address the following questions: (i) what
      is the physiological contribution of pressure natriuresis to the control of total
      body sodium (TBS); (ii) to what extent is long-term mean arterial blood pressure
      (MABP) determined by TBS and total body water (TBW); and (iii) during Na
      accumulation, is Na stored in an osmotically inactive form? 3. Diurnal time
      courses of Na excretion (U(Na)V) and MABP reveal no correlation. Spontaneous MABP
      changes do not affect U(Na)V. The long-term 20% reduction of renal perfusion
      pressure (RPP) results in Na retention via pressure-dependent stimulation of the
      renin-angiotensin-aldosterone system (RAAS), not via a pressure natriuresis
      mechanism. Prevention of pressure natriuresis does not result in ongoing Na
      retention when the RAAS is operative. The long-term 20% elevation of RPP induced
      by sustained TBS elevation facilitates Na excretion via pressure natriuresis, but
      does not restore TBS to normal. 4. Changes in TBW correlate well with changes in
      TBS (r(2) = 0.79). This correlation is even closer when concomitant changes in
      total body potassium are also considered (r(2) = 0.91). 5. With normal or
      elevated TBW, long-term MABP changes correlate well with TBW changes (r(2) =
      0.69). At lowered TBW, no correlation is found. 6. In conclusion, the
      physiological role of pressure natriuresis is limited. Pressure natriuresis does
      not appear to be operative when RPP is changed from -20 to +10% and neurohumoral
      control of U(Na)V is unimpeded. Within this range, pressure-dependent changes in
      the RAAS mediate the effects of changes in RPP on U(Na)V. Pressure natriuresis
      may constitute a compensating mechanism under pathophysiological conditions of
      substantial elevation of RPP. A large portion of the long-term changes in MABP
      are attributable to changes in TBW. The notion of osmotically inactive Na storage
      during Na accumulation appears to be invalid.

PMID- 15854149
TI  - Mechanisms mediating pressure natriuresis: what we know and what we need to find
      out.
AB  - 1. It is well established that pressure natriuresis plays a key role in long-term
      blood pressure regulation, but our understanding of the mechanisms underlying
      this process is incomplete. 2. Pressure natriuresis is chiefly mediated by
      inhibition of tubular sodium reabsorption, because both total renal blood flow
      and glomerular filtration rate are efficiently autoregulated. Inhibition of
      active sodium transport within both the proximal and distal tubules likely makes
      a contribution. Increased renal interstitial hydrostatic pressure (RIHP) likely
      inhibits sodium reabsorption by altering passive diffusion through paracellular
      pathways in 'leaky' tubular elements. 3. Nitric oxide and products of cytochrome
      P450-dependent arachidonic acid metabolism are key signalling mechanisms in
      pressure natriuresis, although their precise roles remain to be determined. 4.
      The key unresolved question is, how is increased renal artery pressure 'sensed'
      by the kidney? One proposal rests on the notion that blood flow in the renal
      medulla is poorly autoregulated, so that increased renal artery pressure leads to
      increased renal medullary blood flow (MBF), which, in turn, leads to increased
      RIHP. An alternative proposal is that the process of autoregulation of renal
      blood flow leads to increased shear stress in the preglomerular vasculature and,
      so, release of nitric oxide and perhaps products of cytochrome P450-dependent
      arachidonic acid metabolism, which, in turn, drive the cascade of events that
      inhibit sodium reabsorption. 5. Central to the arguments underlying these
      opposing hypotheses is the extent to which MBF is autoregulated. This remains
      highly controversial, largely because of the limitations of presently available
      methods for measurement of MBF.

PMID- 15854150
TI  - Angiotensin II-nitric oxide interaction in glomerular arterioles.
AB  - 1. Resistance changes of the afferent and efferent arterioles determine blood
      flow and filtration rate in the kidney. The tone of both vessels results from the
      influence of nerves and humoral and paracrine factors, through a balance of
      constrictor and dilator systems. Angiotensin (Ang) II and nitric oxide (NO) are
      important factors determining vascular tone. 2. In the present review, we show
      that, in addition to the basal production of NO, a specific and significant AngII
      induced release of NO occurs in glomerular arterioles. Data from investigations
      of arteriolar contraction, as well as from fluorescence measurements of NO, in
      the presence of selective angiotensin AT(1) and AT(2) receptor antagonists
      indicate an AT(1) receptor-stimulated release of NO in afferent arterioles. 3.
      The AngII-induced liberation of NO could prevent glomerular arterioles from a
      marked constriction, particularly in situations of high AngII levels in the
      kidney.

PMID- 15854151
TI  - Pathogenesis of hypertension in renal failure: role of the sympathetic nervous
      system and renal afferents.
AB  - 1. The kidney receives a dense innervation of sympathetic and sensory fibres and
      can be both a target of sympathetic activity and a source of signals that drive
      sympathetic tone. In the normal state, interactions between the kidney and
      sympathetic nervous system (SNS) serve to maintain blood pressure and glomerular
      filtration rate within tightly controlled levels. In renal failure, a defect in
      renal sodium excretory function leads to an abnormal pressure natriuresis
      relationship and activation of the renin-angiotensin-aldosterone system,
      contributing to the development of hypertension and progression of kidney
      disease. 2. Evidence now strongly indicates a role for the SNS in the
      pathogenesis of hypertension in renal failure. Hypertension occurs commonly and
      early in renal disease and is paralleled by increases in SNS activity, as
      indicated by increased muscle sympathetic nerve activity and circulating
      catecholamines. This appears to be driven by the diseased kidneys, because
      nephrectomy or denervation has been shown to correct blood pressure and SNS
      activity in human and animal studies. 3. Afferent signals from the kidney,
      detected by chemoreceptors and mechanoreceptors, feed directly into central
      nuclei of the SNS, including the hypothalamus and circumventricular organs, in
      addition to the stimulus provided by circulating and brain-derived angiotensin
      II. Therefore, the pathogenesis of hypertension in renal failure is complex and
      arises from the interaction of haemodynamic and neuroendocrine factors. 4.
      Increased SNS activity has significant implications with regard to increased risk
      of cardiovascular disease and is an important consideration in the treatment of
      renal failure.

PMID- 15854152
TI  - Long-term regulation of arterial blood pressure by hypothalamic nuclei: some
      critical questions.
AB  - 1. The long-term level of arterial pressure is dependent on the relationship
      between arterial pressure and the urinary output of salt and water, which, in
      turn, is affected by a number of factors, including renal sympathetic nerve
      activity (RSNA). In the present brief review, we consider the mechanisms within
      the brain that can influence RSNA, focusing particularly on hypothalamic
      mechanisms. 2. The paraventricular nucleus (PVN) in the hypothalamus has major
      direct and indirect connections with the sympathetic outflow and there is now
      considerable evidence that tonic activation of the PVN sympathetic pathway
      contributes to the sustained increased level of RSNA that occurs in conditions
      such as heart failure and neurogenic hypertension. The tonic activity of PVN
      sympathetic neurons, in turn, depends upon the balance of excitatory and
      inhibitory inputs. A number of neurotransmitters and neuromodulators are involved
      in these tonic excitatory and inhibitory effects, including glutamate, GABA,
      angiotensin II and nitric oxide. 3. The dorsomedial hypothalamic nucleus (DMH)
      also exerts a powerful influence over sympathetic activity, including RSNA, via
      synapses with sympathetic nuclei in the medulla and, possibly, also other
      brainstem regions. The DMH sympathetic pathway is an important component of the
      phasic sympathoexcitatory responses associated with acute stress, but there is no
      evidence that it is an important component of the central pathways that produce
      long-term changes in arterial pressure. Nevertheless, it is possible that
      repeated episodic activation of this pathway could lead to vascular hypertrophy
      and, thus, sustained changes in vascular resistance and arterial pressure. 4.
      Recent studies have reactivated the old debate concerning the possible role of
      the baroreceptor reflex in the long-term regulation of sympathetic activity.
      Therefore, central resetting of the baroreceptor-sympathetic reflex may be an
      important component of the mechanisms causing sustained changes in RSNA. However,
      little is known about the cellular mechanisms that could cause such resetting.

PMID- 15854153
TI  - Translation of salt retention to central activation of the sympathetic nervous
      system in hypertension.
AB  - 1. Increased dietary salt increases blood pressure in many hypertensive
      individuals, producing salt-sensitive hypertension (SSH). The cause is unknown,
      but a major component appears to be activation of the sympathetic nervous system.
      The purpose of this short review is to present one hypothesis to explain how
      increased dietary salt increases sympathetic activity in SSH. 2. It is proposed
      that increased salt intake causes salt retention and raises plasma sodium
      chloride (NaCl) concentrations, which activate sodium/osmoreceptors to trigger
      sympathoexcitation. Moreover, we suggest that small and often undetectable
      increases in osmolality can drive significant sympathoexcitation, because the
      gain of the relationship between osmolality and increased sympathetic activity is
      enhanced. Multiple factors may contribute to this facilitation, including
      inappropriately elevated levels of angiotensin II or aldosterone, changes in gene
      expression or synaptic plasticity and increased sodium concentrations in
      cerebrospinal fluid. 3. Future studies are required to delineate the brain sites
      and mechanisms of action and interaction of osmolality and these amplification
      factors to elicit sustained sympathoexcitation in SSH.

PMID- 15854154
TI  - Long-term recording of sympathetic nerve activity: the new frontier in
      understanding the development of hypertension?
AB  - 1. With increasing evidence that the sympathetic nervous system plays a critical
      role in the development of hypertension, focus is turning to how these signals
      translate to a chronic increase in arterial pressure. 2. The kidney's role in the
      control of salt and water homeostasis makes it an obvious target for such
      investigations. However, to date, many studies have been restricted to
      experiments lasting only a few hours or, at most, a few days, whereas others may
      use indirect methods of assessing sympathetic activity rather than direct
      recordings. 3. We review current approaches used to determine the effects of
      renal sympathetic nerve activity (SNA) on arterial pressure and suggest possible
      avenues of future investigation. We propose that although afferent inputs, such
      as from chemoreceptors and baroreceptors, are important for the short-term
      control of blood pressure via regulation of SNA to multiple organs, it is highly
      likely that alternative signals are important for setting the long-term level of
      renal SNA. 4. Emerging evidence indicates circulating angiotensin II is hormone
      that may act on the central nervous system to regulate renal SNA, renal function
      and, thus, blood pressure. 5. We propose that an integral part of future studies
      seeking an understanding of the genesis of hypertension should include chronic
      direct recordings of renal SNA.

PMID- 15854155
TI  - Nitric oxide and sympathetic nerve activity in the control of blood pressure.
AB  - 1. Endothelial dysfunction marked by impairment in the release of nitric oxide
      (NO) is seen very early in the development of hypertension and is considered
      important in mediating the impaired vascular tone evident in essential
      hypertensive patients. 2. Recently, a hypothesis has emerged that NO acting as a
      neurotransmitter in the brain can modulate levels of sympathetic nerve activity
      and thereby blood pressure. The NO inhibition model of hypertension has been used
      to explore the possibility that a decrease in levels of NO can cause an increase
      in levels of sympathetic nerve activity that can mediate the hypertension. 3. In
      the present review, we examine the literature regarding the role of NO in setting
      the mean level of sympathetic nerve activity and blood pressure. Although the
      acute effects of NO inhibition are well understood, the chronic interaction
      between the sympathetic nervous system and NO has only been investigated using
      indirect measures of sympathetic nerve activity, such as ganglionic blockade.
      This has led to inconsistent results regarding the role of NO in modulating
      sympathetic nerve activity chronically. 4. Some of the conflicting results may be
      explained by differences in the 'background' levels of angiotensin (Ang) II.
      Evidence suggests that NO may interact with AngII and baroreceptor afferent
      inputs in the central nervous system to set the mean level of sympathetic nerve
      activity. 5. We suggest chronic NO inhibition can increase sympathetic nerve
      activity if baroreceptor input is intact and AngII levels are elevated. Although
      studies exploring the actions of NO or AngII in isolation are useful for
      gathering initial information, future studies should focus on their interactions
      and their role in setting the long-term levels of sympathetic activity and blood
      pressure.

PMID- 15854156
TI  - Cardiovascular alterations by chronic intermittent hypoxia: importance of carotid
      body chemoreflexes.
AB  - 1. Humans experiencing intermittent hypoxia (IH) owing to recurrent apnoea
      syndromes exhibit serious cardiovascular morbidity, including high blood
      pressure, increased sympathetic nerve activity, cardiac arrhythmia and myocardial
      infarction. Although apnoeas are accompanied by a simultaneous decrease in
      arterial O(2) (hypoxia) and an increase in CO(2) (hypercapnia), studies on
      experimental animals suggest that hypoxia, rather than hypercapnia, is the
      primary stimulus for developing hypertension and enhanced sympathetic nerve
      activity. Enhanced hypoxic-sensing ability of the carotid bodies and the ensuing
      reflex activation of the sympathetic nervous system have been suggested to play a
      critical role in cardiorespiratory alterations resulting from recurrent apnoeas.
      2. The purpose of the present review is to highlight recent studies demonstrating
      the effects of IH on carotid body sensory activity and its consequences on
      sympathetic activation in a rodent model of chronic IH. Adult rats exposed to
      chronic IH (15 s of 5% O(2) followed by 5 min of 21% O(2), nine episodes per h, 8
      h/day for 10 days) exhibited selective enhancement of carotid body sensory
      response to hypoxia. In addition, chronic IH induced a novel form of sensory
      plasticity in the carotid body, manifested as sensory long-term facilitation
      (LTF). Functional changes in the carotid body occurred in the absence of
      morphological changes in the chemoreceptor tissue. 3. Acute hypoxia increased
      expiratory modulated splanchnic nerve activity (SNA) and acute IH-induced LTF in
      SNA. Hypoxia-induced SNA activation was prevented by bilateral sectioning of the
      sinus nerves. Rats exposed to chronic IH exhibited enhanced hypoxia-induced
      sympathetic activation and augmented LTF of the SNA. Bilateral sectioning of the
      sinus nerves abolished these responses, suggesting chronic IH-induced alterations
      in carotid body sensitivity contribute to LTF in SNA and the subsequent
      cardiovascular alterations.

PMID- 15854157
TI  - Role of the central nucleus of the amygdala in the control of blood pressure:
      descending pathways to medullary cardiovascular nuclei.
AB  - 1. One of the key areas that links psychologically induced stress with the blood
      pressure-regulatory system is the central nucleus of the amygdala (CeA). This is
      an integratory forebrain nucleus that receives input from higher centres in the
      forebrain and has extensive connections with the hypothalamus and the medulla
      oblongata, areas involved in the regulation of the cardiovascular reflexes. 2.
      Based on studies using electrical or chemical stimulation or electrolytic lesions
      of the CeA, it has become clear that the CeA plays an important role in the
      regulation of blood pressure in response to stressful or fearful stimuli. 3. Two
      important medullary areas known to receive projections from the CeA are the
      nucleus tractus solitarius (NTS) and the rostral ventrolateral medulla (RVLM).
      The NTS is the site of the first synapse for afferent fibres originating from
      baroreceptors, chemoreceptors and the heart, whereas the RVLM contains neurons
      that maintain resting blood pressure and sympathetic nerve activity via
      projections to sympathetic preganglionic neurons in the intermediolateral cell
      column of the thoracolumbar spinal cord. 4. Electron microscopic studies using
      combined anterograde tracing and pre- and post-embedding immunogold labelling
      have shown that the pathways originating from the CeA to the NTS are inhibitory
      and may use GABA as a neurotransmitter. The results of these studies suggest that
      blood pressure changes produced by activation of the CeA may be mediated by
      attenuation of baroreceptor reflexes through a GABAergic mechanism at the level
      of the NTS. 5. Neuronal tract tracing combined with neurofunctional studies using
      the Fos protein as a marker of activated neurons indicate that the CeA projects
      directly to baroreceptive neurons in the NTS and RVLM that are activated by
      changes in blood pressure. 6. In conclusion, studies that have examined the
      efferent pathways of the CeA suggest that CeA neurons with projections to
      medullary baroreceptive neurons may play a vital role in the reflex changes in
      sympathetic nerve activity that are involved in blood pressure regulation in
      response to stress or anxiety.

PMID- 15854158
TI  - Thermoregulatory role of periventricular tissue surrounding the anteroventral
      third ventricle (AV3V) during acute heat stress in the rat.
AB  - 1. Thermoregulatory effector mechanisms are strongly influenced by hydration
      status. Dehydration delays the onset of evaporative heat loss and the
      redistribution of cardiac output in response to elevations in core temperature,
      yet very little is known about how and where thermal and non-thermal information
      is integrated. 2. The anteroventral third ventricular (AV3V) region encompasses
      several distinct neural structures, including the organum vasculosum of the
      lamina terminalis, the median preoptic nucleus, the preoptic periventricular
      nucleus and the medial aspects of the medial preoptic nucleus. In addition to its
      well-documented role in body fluid and cardiovascular homeostasis, recent
      anatomical and in vitro evidence has indicated the AV3V region may also be
      pivotal in the integration of thermal and osmotic information. 3. Electrolytic
      lesions of the AV3V region produce a markedly reduced thermal tolerance in rats.
      Elevations in mean arterial pressure, heart rate and mesenteric resistance were
      all attenuated in the AV3V-lesioned animals in response to a heat stress;
      however, hindquarter resistance was unaffected. Heat-induced salivation was also
      attenuated, severely reducing the ability of rats to lose heat via evaporation.
      4. The AV3V region clearly has a functional role in thermoregulation, as well as
      cardiovascular and body fluid homeostasis. These data add further support to the
      hypothesis that thermal and non-thermal information may be integrated within this
      region.

PMID- 15854159
TI  - Chronic effects of angiotensin II and at1 receptor antagonists in subfornical
      organ-lesioned rats.
AB  - 1. Angiotensin (Ang) II is known to exert some of its effects centrally via
      circumventricular organs. These unique central nervous system areas lack the
      normal blood-brain barrier and, therefore, allow peptide hormones access to the
      brain. Of these, the subfornical organ (SFO) has been shown to be involved in
      many of the acute dipsogenic and pressor effects of AngII, but much less is known
      about the role of the SFO in the chronic effects of AngII. We hypothesized that
      the SFO is a central site involved in the chronic hypotensive effects of
      endogenous AT(1) receptor blockade, as well as the chronic hypertensive effects
      of exogenously administered AngII. 2. In order to test these hypotheses, SFO
      lesioned (SFOx) or sham Sprague-Dawley rats were instrumented with venous
      catheters and radiotelemetric pressure transducers for intravenous administration
      of losartan or AngII and continuous measurement of blood pressure and heart rate.
      Rats were given 3 days of saline control infusion (7 mL/day of 0.9% NaCl) and
      were then infused with either losartan (10 mg/kg per day) or AngII (10 ng/kg per
      min) for 10 days. 3. By day 4 of losartan treatment, arterial pressure had
      decreased 24 +/- 2 and 18 +/- 2 mmHg in sham (n = 9) and SFOx (n = 10) rats,
      respectively. Furthermore, by day 5 of AngII infusion, arterial pressure had
      increased 12 +/- 3 mmHg in sham rats (n = 9), but only by 4 +/- 1 mmHg in SFOx
      rats (n = 9). In each treatment group, these attenuated pressure responses in
      SFOx rats continued through day 10 of treatment. 4. These results support the
      hypotheses that the SFO plays a role in both the hypotensive effects of chronic
      AT(1) receptor blockade and the chronic hypertensive phase of exogenously
      administered AngII.

PMID- 15854160
TI  - Autonomic and respiratory responses to microinjection of ATP into the
      intermediate or caudal nucleus tractus solitarius in the working heart-brainstem
      preparation of the rat.
AB  - 1. Activation of peripheral chemoreceptors with KCN in the working heart
      brainstem preparation from young male Wistar rats (70-90 g) increases phrenic
      (PNA; +105 +/- 18%) and thoracic (tSNA; +44 +/- 6%) sympathetic nerve activity
      compared with baseline and reduces heart rate (HR; from 377 +/- 27 to 83 +/- 6
      b.p.m.). 2. Microinjections of increasing doses of ATP (1, 5, 25, 100 and 500
      mmol/L; n = 7) into the intermediate nucleus tractus solitarius (NTS) produced a
      dose-dependent reduction in PNA (from -6 +/- 3 to -82 +/- 1%) and in HR (from -12
      +/- 4 to -179 +/- 47 b.p.m.). Microinjections of ATP into the intermediate NTS
      also produced a reduction in tSNA (from -3 +/- 3 to -26 +/- 5%), which was not
      dose dependent. 3. Microinjections of ATP into the caudal NTS (n = 5) produced a
      dose-dependent increase in PNA (from 0.2 +/- 3 to 115 +/- 27%) and minor changes
      in HR and tSNA, which were not dose dependent. 4. The data show that
      microinjection of ATP into distinct subregions of the NTS produces different
      respiratory and autonomic responses and suggest that ATP in the caudal NTS is
      involved in the respiratory but not in the sympathoexcitatory component of the
      chemoreflex.

PMID- 15854161
TI  - A neglected 'accessory' vasomotor pathway: implications for blood pressure
      control.
AB  - 1. Distinct from 'regular' sympathetic preganglionic neurons, there exists a
      population of 'accessory' preganglionic neurons. The latter are distinguishable
      by their unmyelinated axons and their different functional properties. They
      synapse on the same ganglion cells. 2. Ongoing sympathetic activity is driven by
      'regular' preganglionic neurons. 3. 'Accessory' preganglionic neurons drive
      hexamethonium-resistant ganglionic transmission: part of this is muscarinic and
      part not (possibly peptidergic or nitrergic). 4. 'Accessory' preganglionic
      neurons supply cardiovascular (vasomotor, cardiac, adrenal), but apparently not
      other, sympathetic pathways. 5. 'Accessory' preganglionic neurons are activated
      by arterial chemoreceptors. 6. Brief activation of 'accessory' preganglionic
      neurons potentiates ongoing post-ganglionic activity for tens of minutes by an
      action at the ganglion. This is probably by enabling previously subthreshold
      excitatory post-synaptic potentials to trigger action potentials. 7. Evidence is
      presented that microinjections of GABA into the rostral ventrolateral medulla
      activate the 'accessory' pathway while inhibiting the 'regular' pathway. 8. A
      role for this 'accessory' pathway in the long-term control of blood pressure in
      health and disease is predicted, but still untested.

PMID- 15854162
TI  - Decreased vasodilation induced by a new nitric oxide donor in two kidney, one
      clip hypertensive rats is due to impaired k channel activation.
AB  - 1. We studied the effect of the new compound trans-[RuCl([15]aneN(4))NO](2+) (15
      ane) in denuded aortic rings of two kidney (2K) normotensive and two kidney, one
      clip (2K-1C) hypertensive rats. 2. The compound 15-ane releases nitric oxide (NO)
      when reduced by a catecholamine (noradrenaline). 3. Oxyhemoglobin (HbO(2)), an NO
      scavenger, completely abolished the effect of 15-ane in both 2K and 2K-1C rats,
      indicating that the relaxation is really due to NO release. 4. We tested the
      hypothesis that an impairment of K(+) channels plays an important role in the
      vasodilation induced by 15-ane. 5. The selective inhibitor of soluble guanylyl
      cyclase, namely 1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ; 1
      micromol/L) reduced the relaxation induced by 15-ane. In 2K-1C rat aortic rings,
      ODQ reduced the maximum effect (E(max)) of 15-ane, whereas in 2K rat aortic rings
      ODQ reduced E(max) and pD(2) values to 15-ane. 6. The selective K(+) channel
      blockers glibenclamide (blocks K(ATP); 3 micromol/L), 4-aminopyridine (blocks
      K(V); 1 mmol/L) and the small conductance K(Ca) channel blocker apamin (1
      micromol/L) reduced E(max) and pD(2) values for 15-ane-induced relaxation
      responses of aortas from 2K rats. However, iberiotoxin, a blocker of large
      conductance K(Ca) channels, reduced only the E(max) to 15-ane. None of these K(+)
      channel blockers had any effect on the relaxation induced by 15-ane of aortas
      from 2K-1C rats. 7. These data indicate that an impaired functional activity of
      K(+) channels contributes to the deficient relaxation induced by the NO donor 15
      ane in renal hypertensive 2K-1C rat aortas.

PMID- 15854163
TI  - Role of endothelium-derived hyperpolarizing factor in endothelial dysfunction
      during diabetes.
AB  - 1. Under normal conditions, the endothelium plays a major role in the maintenance
      of vasodilatory tone via the production of endothelium-derived vasodilator
      agents, such as prostacyclin, nitric oxide and endothelium-derived
      hyperpolarizing factor (EDHF). Inhibition of endothelium-dependent relaxation
      features prominently in a range of cardiovascular diseases, including
      hypertension, coronary artery disease and diabetes. 2. Endothelium-derived
      hyperpolarizing factor is a prominent vasodilator, particularly in smaller
      arteries and arterioles. There is now emerging evidence to suggest that EDHF may
      play a role in the endothelial dysfunction in diabetes. 3. Since the first
      description of endothelium-dependent hyperpolarization some 20 years ago, it has
      emerged that EDHF is heterogeneous in nature, consisting of diffusible factors
      and contact-mediated mechanisms. The specific identity of EDHF in any particular
      vascular bed may influence the impact of diabetes on vascular function. 4. There
      is accumulating evidence in diabetic rat models and humans showing impaired EDHF
      activity in small resistance vessels. In contrast, studies in mice suggest that
      EDHF activity is actually enhanced under diabetic conditions. 5. It is clear that
      alterations in EDHF activity may have an important contribution in diabetes, more
      specifically in contributing to microvascular complications observed under
      diabetic conditions.

PMID- 15854164
TI  - Cardiovascular autonomic regulation in subjects with normal blood pressure, high
      normal blood pressure and recent-onset hypertension.
AB  - 1. In the present study, we tested the hypothesis that heart rate variability
      (HRV) is reduced in recent-onset hypertension and that pressor responses to
      standard autonomic reflex tests are not any different in hypertensives compared
      with normotensives. We also hypothesized that subjects with high-normal blood
      pressure (BP) would be distinguishable from normotensives on the basis of short
      term HRV indices. 2. Three groups of subjects, each consisting of 15 men and 10
      women, were examined. The first group consisted of subjects with recent-onset
      hypertension who were not taking antihypertensive medication (mean (+/-SD) age 50
      +/- 12 years; BP >/= 140/90 mmHg), the second group consisted of subjects with
      high-normal BP (mean age 46 +/- 13 years; BP 130-139/85-89 mmHg) and the third
      group consisted of subjects with normal BP (mean age 48 +/- 12 years; BP < 120/80
      mmHg). The aim was to characterize the autonomic state in each group. 3. Blood
      pressure, heart rate (HR), indices of short-term HRV during supine rest and quiet
      standing, HR variation during timed deep breathing (HRVdb) and pressor responses
      to the cold pressor test and sustained isometric handgrip were compared between
      the groups. 4. Although the three groups were comparable (P > 0.1) in terms of
      mean HR and low-frequency (LF) power expressed in normalized units at rest and
      during quiet standing, the standard deviation of normal-to-normal RR intervals
      (SDNN) during supine rest, LF and high-frequency spectral powers during supine
      rest and HRVdb were lowest in hypertensives (P </= 0.05 for each), indicating
      diminished baroreflex modulation of RR intervals in hypertensives. 5. In
      contrast, LF power was highest in subjects with high-normal BP (P </= 0.05)
      during supine rest and this is possibly because of higher BP variability. 6. The
      results suggest that HRVdb provides a simple measure of cardiac vagal effects in
      hypertensives, the rate-pressure product provides a simple measure of overall HRV
      in hypertensives and, in clinical hypertension, the arterial baroreflex mechanism
      is reset to maintain a higher BP through diminished vagal modulation of HR and
      possibly heightened sympathetic outflow to the heart and resistance vessels.

PMID- 15854165
TI  - A haplotype of the angiotensinogen gene is associated with hypertension in
      african americans.
AB  - 1. Hypertension is a serious risk factor for myocardial infarction, heart
      failure, vascular disease, stroke and renal failure. The incidence of
      hypertension is 25-30% in the adult Caucasian population and complications due to
      hypertension are even greater in African Americans. 2. The renin-angiotensin
      system plays an important role in the regulation of blood pressure and previous
      studies have suggested that angiotensinogen (AGT) gene locus is linked with human
      essential hypertension. Earlier studies suggested that a single nucleotide
      polymorphism (SNP) that converts methionine to threonine at amino acid 235 is
      associated with hypertension in the Caucasian population. However, this SNP is
      not associated with hypertension in African American and Chinese populations. 3.
      We have found an A/G polymorphism at -217 of the human AGT gene promoter and have
      shown that the frequency of allele A at -217 is significantly increased in the
      genomic DNA of African American hypertensive patients. 4. We have also shown
      that: (i) reporter constructs containing the AGT gene promoter with nucleoside A
      at -217 have increased promoter activity on transient transfection; and (ii) the
      CCAAT box enhancer binding protein (C/EBP) family of transcription factors and
      glucocorticoid receptor (GR) bind preferentially to this region of the promoter
      when nucleoside A is present at -217. In addition, variant -217A is always
      present with variants -532T, -793A and -1074T in the human AGT gene promoter. 5.
      These data suggest that the AGT haplotype containing -217A, -532T, -793A and 
      1074T may be involved in increased transcription of this gene and may play a role
      in human hypertension.

PMID- 15854166
TI  - Systematic review and meta-analysis: enhanced efficacy of proton-pump inhibitor
      therapy for peptic ulcer bleeding in Asia--a post hoc analysis from the Cochrane
      Collaboration.
AB  - BACKGROUND: Proton-pump inhibitors reduce re-bleeding rates after ulcer bleeding.
      However, there is significant heterogeneity among different randomized-controlled
      trials. AIM: To see whether proton-pump inhibitors for ulcer bleeding produced
      different clinical outcomes in different geographical locations. METHODS: This
      was a post hoc analysis of our Cochrane Collaboration systematic review and meta
      analysis of proton-pump inhibitor therapy for ulcer bleeding. Sixteen randomized
      controlled trials conducted in Europe and North America were pooled and re
      analysed separately from seven conducted in Asia. We calculated pooled rates for
      30-day all-cause mortality, re-bleeding and surgical intervention and derived
      odds ratios and numbers needed to treat with 95% confidence intervals. RESULTS:
      There was no significant heterogeneity for any outcome. Reduced all-cause
      mortality was seen in the Asian randomized-controlled trials (odds ratios = 0.35;
      95% confidence interval: 0.16-0.74; number needed to treat = 33), but not in the
      others (odds ratios = 1.36; 95% confidence interval: 0.94-1.96; number needed to
      treat--incalculable). There were significant reductions in re-bleeding and
      surgery in both sets of randomized-controlled trials, but the effects were
      quantitatively greater in Asia. CONCLUSIONS: Proton-pump inhibitor therapy for
      ulcer bleeding has been more efficacious in Asia than elsewhere. This may be
      because of an enhanced pharmacodynamic effect of proton-pump inhibitors in Asian
      patients.

PMID- 15854167
TI  - Infliximab reverses growth hormone resistance associated with inflammatory bowel
      disease.
AB  - BACKGROUND: Increasing evidence shows that inflammation plays a major role in the
      aetiology of catabolism and wasting observed in inflammatory bowel disease via
      growth hormone resistance. AIM: To evaluate the effect of infliximab treatment on
      the growth hormone/insulin-like growth factor-1 axis. METHODS: Fourteen adults
      with active Crohn's disease or ulcerative colitis underwent three infliximab
      infusions at a dose of 5 mg/kg for induction of remission, plus two maintenance
      infusions 8 weeks apart. Blood samples were collected for the analysis of serum
      growth hormone, insulin-like growth factor-1, insulin-like growth factor-binding
      protein-3 and acid labile subunit. RESULTS: Serum insulin-like growth factor-1
      and insulin-like growth factor-binding protein-3 concentrations, which were
      significantly lower in inflammatory bowel disease patients before treatment
      compared with controls (P < 0.01), significantly increased during the induction
      phase (+58% and +29%, respectively, after the second infusion, P < 0.01), and
      dropped to baseline levels during maintenance therapy. Both insulin-like growth
      factor-1 and insulin-like growth factor-binding protein-3 showed significant
      negative correlations with C-reactive protein (rho = -0.37, P = 0.002; rho = 
      0.35, P = 0.01, respectively). Growth hormone and acid labile subunit levels were
      not statistically different between controls and inflammatory bowel disease
      patients either at baseline or during treatment. CONCLUSIONS: Infliximab
      induction treatment reverses growth hormone resistance observed in active
      inflammatory bowel disease through the suppression of systemic inflammation. The
      restored growth hormone/insulin-like growth factor-1 axis is impaired again
      following the prolonged interval between maintenance infusions, possibly because
      of the subclinical reactivation of the inflammatory process.

PMID- 15854168
TI  - Seasonality of vitamin D status and bone turnover in patients with Crohn's
      disease.
AB  - BACKGROUND: While winter-time vitamin D deficiency has been well-documented in
      Crohn's disease patients, less is known about vitamin D status during summertime
      and whether a seasonal variation exists in bone turnover. AIMS: To compare
      vitamin D status and bone turnover markers in Crohn's disease patients with age-
      and sex-matched controls during late-summer and late-winter. SUBJECTS: Crohn's
      disease patients (n = 44; mean age 36.9 years, currently in remission) and
      matched controls (n = 44) were recruited from Cork University Hospital and Cork
      City area, respectively. METHODS: Bloods were analysed for 25-hydroxyvitamin D,
      parathyroid hormone, bone-specific alkaline phosphatase, osteocalcin and urine
      analysed for N-telopeptides of type 1 collagen. RESULTS: Serum 25-hydroxyvitamin
      D concentrations were significantly (P < 0.003) lower in Crohn's disease patients
      than in control subjects during both seasons. In Crohn's disease patients, serum
      25-hydroxyvitamin D concentrations were lower (P < 0.0001) whereas serum
      parathyroid hormone, osteocalcin and bone-specific alkaline phosphatase and
      urinary N-telopeptides of type 1 collagen levels were higher (P < 0.001) during
      late-winter than late-summer. CONCLUSION: There were notable seasonal variations
      in vitamin D status and bone turnover markers in Crohn's disease patients. The
      impact of winter decline in vitamin D status and increase in bone turnover on
      long-term risk of osteopenia/osteoporosis in Crohn's disease patients is unclear.

PMID- 15854169
TI  - The significance of rectal bleeding after pelvic radiotherapy.
AB  - BACKGROUND: Rectal bleeding after pelvic radiotherapy is often attributed to
      radiation proctitis and patients do not routinely undergo flexible endoscopy.
      AIMS: To assess the significance of bleeding after radiotherapy. METHODS: We
      maintained a prospective register of all such patients referred to our endoscopy
      unit. RESULTS: One hundred and thirty-nine men (median age 70 years; range 31
      82), and 32 women (median age 61 years; range 30-81) were referred with rectal
      bleeding (median 2 years; range 0-21) after pelvic radiotherapy. Primary tumour
      sites were urological (n = 139), gastrointestinal (n = 7) and gynaecological (n =
      25). Ninety patients had bleeding alone; 81 had other symptoms. One hundred and
      forty-one had typical radiation proctitis; in 65 this was the sole diagnosis;
      eight had cancer, nine had high-risk adenomas, and six had three or more small
      adenomas. Ninety-five other diagnoses were made. Eleven (73%) patients with
      advanced polyps or cancer required only flexible sigmoidoscopy to make the
      diagnosis, while four (27%) diagnoses were made only after colonoscopy; 47% of
      these patients had no other symptoms apart from rectal bleeding. CONCLUSIONS:
      After pelvic radiotherapy, clinical symptoms are not reliable in differentiating
      between radiation proctitis alone or more significant pathology. It is mandatory
      that all patients with new onset rectal bleeding are investigated with, at least,
      flexible sigmoidoscopy.

PMID- 15854170
TI  - Inflammatory gene signature in ulcerative colitis with cDNA macroarray analysis.
AB  - BACKGROUND: Most array analyses of ulcerative colitis have focused on identifying
      susceptibility genes for ulcerative colitis. AIM: To clarify the changes in gene
      expression during inflammation in ulcerative colitis colon mucosa using cDNA
      macroarray. METHODS: From 23 ulcerative colitis patients, 16 each of inflamed and
      non-inflamed specimens (total 32 samples for individual analysis) were obtained
      by colonoscopic biopsy. Eighteen of the 32 samples, used for pairwise analysis,
      consisted of nine sample pairs, each pair being from the same patient. We
      examined expression profiles of approximately 1300 genes with cDNA macroarray.
      Comparisons were made using two kinds of statistics, t-test and significance
      analysis of microarray in both analyses. The reproducibility of significant genes
      from the macroarray analysis was confirmed by real-time ploymerase chain
      reaction. RESULTS: We detected five upregulated genes, categorized into
      proinflammatory genes (MRP14, GRO gamma and SAA1) and anti-inflammatory genes
      (TIMP1 and Elafin) in inflamed mucosa, and one upregulated gene (L-FABP) in non
      inflamed mucosa. CONCLUSIONS: As the cDNA macroarray analysis in this study
      exactly reflects the total profile of gene expression in the clinical setting of
      ulcerative colitis, the genes identified will be directly applicable to
      diagnostics or as novel therapeutic targets in active ulcerative colitis.

PMID- 15854171
TI  - Multicentre randomized-controlled clinical trial of Ipocol, a new enteric-coated
      form of mesalazine, in comparison with Asacol in the treatment of ulcerative
      colitis.
AB  - BACKGROUND: 5-Aminosalicylates remain important in the treatment of ulcerative
      colitis, but it is uncertain if the various preparations currently available are
      equivalent given the different delivery systems that exist. Generic prescription
      of mesalazine (mesalamine) is therefore inappropriate. Ipocol has recently become
      available as an alternative to Asacol-MR. AIM: To compare the two agents in a
      controlled trial using a non-inferiority design. METHODS: Eighty-eight ulcerative
      colitis patients with a mild to moderate clinical relapse were randomized to one
      of the two drugs at a daily dose of 2.4 g for 8 weeks. Safety was the key
      concern; the primary measured end-point was efficacy as judged from a colitis
      activity index. RESULTS: There were no unexpected adverse events of clinical
      consequence. The colitis score improved similarly in both patient groups (by 2.3
      with Ipocol and by 1.5 with Asacol: not significant), and a similar proportion
      was in clinical remission at the end of the study (26.1% for Ipocol and 28.6% for
      Asacol: not significant). Systemic steroids were needed in 11.9% of the Asacol
      treated patients compared with 6.5% with Ipocol (not significant). CONCLUSION: It
      appears appropriate to conclude that, while not identical to Asacol-MR, Ipocol
      offers a safe and similarly effective alternative.

PMID- 15854172
TI  - Effects of aminosalicylates on thiopurine S-methyltransferase activity: an ex
      vivo study in patients with inflammatory bowel disease.
AB  - BACKGROUND: Based on in vitro experiments using recombinant human thiopurine S
      methyltransferase this enzyme is inhibited by sulfasalazine (sulphasalazine) and
      5-aminosalicylate. Thus, during treatment with azathioprine or mercaptopurine,
      both metabolized by thiopurine S-methyltransferase, sulfasalazine or 5
      aminosalicylate could modify the action of azathioprine/mercaptopurine. AIMS: To
      examine whether this interaction is effective under ex vivo conditions. METHODS:
      In 18 azathioprine-free patients and in 12 patients on azathioprine the
      inhibitory potential of sulfasalazine, 5-aminosalicylate and its metabolite (Ac-5
      aminosalicylate) was assessed by ex vivo measurement of thiopurine S
      methyltransferase in red blood cells. RESULTS: According to concentration
      response curves mean IC50 values (microm) for sulfasalazine, 5-aminosalicylate
      and Ac-5-aminosalicylate have been calculated in three groups of azathioprine
      free patients and variable basal levels of thiopurine S-methyltransferase
      activity (very high, normal and intermediate). In all three groups sulfasalazine
      was the strongest inhibitor (IC50: 9-17 microm) if compared with 5
      aminosalicylate (129-236) and Ac-5-aminosalicylate (58-74). In patients on
      azathioprine similar IC50 values have been calculated. CONCLUSIONS: Comparing
      human plasma concentrations of sulfasalazine (15-77 microm), 5-aminosalicylate (3
      14 microm) and Ac-5-aminosalicylate (8-18 microm) with the IC50 values one can
      assume that only sulfasalazine would have the potential to inhibit thiopurine S
      methyltransferase in vivo. However, the therapeutic impact should be proved by
      clinical studies.

PMID- 15854173
TI  - Comparison of two different daily dosages (2.4 vs. 1.2 g) of oral mesalazine in
      maintenance of remission in ulcerative colitis patients: 1-year follow-up study.
AB  - BACKGROUND: Mesalazine as maintenance therapy in ulcerative colitis is used
      worldwide and has been proven to be effective. However, the optimal dosage
      remains to be defined. AIM: To establish whether daily treatment with 2.4 g of
      oral mesalazine is more effective than 1.2 g in preventing disease relapse.
      METHODS: A total of 156 patients with ulcerative colitis in remission were
      randomly treated for 1 year with 2.4 (n = 80) or 1.2 (n = 76) g/day of
      mesalazine. Activity of disease was assessed by periodical clinical, endoscopic
      and histological examinations. RESULTS: After 12 months, 24 of 80 patients (30%)
      on 2.4 g and 20 of 76 patients (26%) on 1.2 g were still in remission (P = N.S.).
      Patients in 2.4 g group remained in remission for a longer time than those in 1.2
      g group (P < 0.001). Among clinical variables considered in the study, course of
      disease prior to enrollment (< or = 3 or > 3 relapses/year) was found to
      influence response to therapy. CONCLUSIONS: A daily dosage of 2.4 g of oral
      mesalazine seems to better at preventing and delaying relapses of ulcerative
      colitis than 1.2 g. The course of disease seems to be crucial in choosing the
      optimal dosage of mesalazine in a maintenance regimen.

PMID- 15854174
TI  - Clinical features of gastric cancer discovered after successful eradication of
      Helicobacter pylori: results from a 9-year prospective follow-up study in Japan.
AB  - BACKGROUND: Eradication of Helicobacter pylori is expected to prevent the
      development of gastric cancer. However, gastric cancer is sometimes discovered
      after successful eradication of H. pylori. AIM: To conduct a prospective study to
      determine the clinical features of patients who underwent successful eradication
      and were later diagnosed with gastric cancer. METHODS: A total of 1787 patients
      (1299 males and 488 females; mean age, 58.2 years; range: 15-84) who underwent
      successful eradication therapy between April 1994 and March 2001 were our study
      subjects. RESULTS: Gastric cancer occurred at a rate of 1.1% (20 of 1787) during
      the follow-up period. Gastric cancer comprises six of 105 (5.7%) with early
      gastric cancer after endoscopic resection, 12 of 575 (2.1%) with gastric ulcer
      and two of 453 (0.4%) with atrophic gastritis. Gastric cancer did not develop in
      any patient with duodenal ulcer. All patients with gastric cancer had baseline
      severe atrophic gastritis in the corpus. CONCLUSION: Careful endoscopic
      examination is necessary even after successful eradication of H. pylori in
      patients with early gastric cancer or gastric ulcer with severe mucosal atrophy
      in the corpus.

PMID- 15854175
TI  - Symptoms of gastro-oesophageal reflux disease and the severity of obstructive
      sleep apnoea syndrome are not related in sleep disorders center patients.
AB  - BACKGROUND: Studies suggest obstructive sleep apnea syndrome (OSAS) frequently
      manifests in patients with gastroesophageal reflux disease (GERD) and that there
      may be a causal relationship. AIM: To determine the relationship between OSAS and
      symptoms of GERD. METHODS: Consecutive patients referred to the Sleep Disorders
      Center (SDC) 18 years and older with polysomnographically defined OSAS were
      evaluated prospectively for GERD using a validated symptoms questionnaire. The
      GERD and OSAS relationship was assessed by 1) determining frequency of GERD in
      patients with and without OSAS; 2) ascertaining the relationship between OSAS
      severity categories and presence of GERD; 3) examining GERD score in relation to
      those factors that might affect both GERD and OSAS, e.g. obesity. RESULTS: One
      thousand and twenty-three SDC patients met entry criteria. Amongst participants,
      GERD was common (29% of women and 17% of males) and OSAS extremely common (58% of
      women and 80% of males). GERD score did not correlate with OSAS variables. The
      severity of OSAS did not influence the prevalence of GERD. CONCLUSION: In a large
      group of patients referred to a sleep disorders center, there was no relationship
      between OSAS and GERD symptoms. Also, there was no relationship between the
      severity of OSAS and the likelihood of GERD symptoms.

PMID- 15854176
TI  - Managing dyspepsia without alarm signs in primary care: new national guidance for
      England and Wales.
AB  - AIM: To report new recommendations for the primary care management of dyspepsia
      without alarm signs in England and Wales. METHOD: An independent, representative
      group of health care professionals, patient representatives and researchers
      developed the guideline using evidence-based and small group-working principles,
      and incorporated extensive peer-reviewing and feedback from stakeholder
      organizations. RESULTS: Referral to investigate dyspepsia should be made for
      alarm signs and not on the basis of age alone, reflecting the balance of benefit
      and harm from endoscopy. Empirical management without formal diagnosis is
      appropriate for most patients: reviewing patient history, lifestyle, over-the
      counter medicines, and providing a course of proton-pump inhibitors and/or
      Helicobacter pylori test and treatment. Patients with ongoing symptoms require at
      least annual review to discuss symptoms and lifestyle, and as appropriate,
      encourage stepping down prescribed medication and returning to self-care. A new
      strategy included in the step down process is the use of therapies 'on-demand'.
      CONCLUSION: The guideline provides structured and supported recommendations for
      both undiagnosed and endoscopically investigated dyspepsia. Some favour increased
      investigation to detect Barrett's oesophagus and carcinoma. However, there is
      inconclusive evidence that patients without alarm signs will benefit subsequently
      from endoscopy, while investigation involves a small but real risk of harm.

PMID- 15854177
TI  - Effect of different organic acids (citric, malic and ascorbic) on intragastric
      urease activity.
AB  - BACKGROUND: The mechanism of citric acid-enhanced Helicobacter pylori urease
      activity remains unclear. AIM: To compare ascorbic, citric and malic acid given
      at the same concentration and pH on intragastric urease activity. METHODS:
      Volunteers received 40 mg of famotidine the evening prior to breath testing.
      After an overnight fast volunteers were randomized to receive 100 mL of water or
      100 mm citric, malic, or ascorbic acid, pH 2.3 containing 75 mg of 13C-urea. At
      15 min a second 100 mL solution of one of the test solutions was taken without
      added urea. RESULTS: Twelve volunteers were studied (eight men, four women, age
      19-57, median 50.7) in a randomized-crossover study. The mean breath test result
      at 30 min with ascorbic (17.5 +/- 5), malic (25.8 +/- 5) and citric acid (29.5 +/
      5) were all significantly greater than with water (9.5 +/- 3). Citric and malic
      acid were similar (P = 0.699) and significantly greater than ascorbic acid (P <
      0.02). When the ascorbic acid was followed by citric acid, the result was similar
      to that with citrate alone (25.8 +/- 4) and greater than with ascorbic then
      ascorbic (P = 0.026). CONCLUSIONS: Enhancement of H. pylori urease activity is
      not strictly a function of the pH. We propose the effect is related to
      differential effects of the availability of nickel, which is required for urease
      activity. Citric acid and malic acid were essentially equivalent such that malic
      acid could substitute for citric acid in the UBT; ascorbic acid would be a poor
      choice.

PMID- 15854178
TI  - Why do complications of gastrointestinal disease and procedures come as serial
      rather than singular events?
AB  - BACKGROUND: It often appears as if complications arising from gastrointestinal
      disease and interventional procedures come in 'series' and 'cluster' in
      individual patients. AIM: The aim of this study was to analyse the clustering of
      complications in terms of stochastic modelling and Markov chains. METHODS: A
      patient with gastrointestinal disease is simulated to move along either a 'bad
      track' associated with multiple consecutive complications or a 'good track' free
      of complications, the transitions within each track and between the two tracks
      being governed by probability values. RESULTS: Because the occurrence of a single
      complication increases the risk of further complications, subjects who encounter
      their first complication are more likely to experience a second, third or even
      more complications, before they leave the 'bad track' and their personal chain of
      cascading complications becomes discontinued. The model of a Markov chain
      explains why the overall number of complications in the total population of
      patients with digestive disease remains low even if individual patients are
      expected to encounter more than a single complication. CONCLUSIONS: Published
      complication rates for gastrointestinal procedures underestimate the true risk to
      the patient, because they do not consider the added vulnerability to cascading
      complications after the first event.

PMID- 15854179
TI  - Predicting which patients can resume oral nutrition after percutaneous endoscopic
      gastrostomy tube placement.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy tubes are placed with high
      frequency and relative safety for a variety of indications. One of these
      indications is temporary nutritional support for patients expected to resume oral
      nutrition. AIMS: To determine if baseline clinical characteristics can predict
      which patients attain the clinical goal of resuming oral nutrition with
      consequent tube removal. METHODS: We conducted a single site observational cohort
      study from December 1999 to April 2001, enrolling all patients scheduled for
      percutaneous endoscopic gastrostomy placement. Standard descriptive and bivariate
      analyses were performed. Cox proportional hazard models were constructed to
      identify patient characteristics prior to percutaneous endoscopic gastrostomy
      placement that might predict resumption of oral nutrition with tube removal.
      RESULTS: Bivariate analyses revealed four potential clinical predictors: age < 65
      years, localized head and neck cancer, serum albumin > or = 3.75 g/dL, and serum
      creatinine < or = 1.1 mg/dL. In multivariable analysis, age < 65 years (HR = 3.7,
      95% CI: 1.0-14.3) and a diagnosis of localized head and neck cancer (HR = 4.6,
      95% CI: 1.4-15.0) predicted resumption of oral nutrition with percutaneous
      endoscopic gastrostomy removal. CONCLUSIONS: When discussing percutaneous
      endoscopic gastrostomy placement, doctors should consider the likelihood of
      achieving clinically important outcomes such as the resumption of oral nutrition
      with tube removal. This clinical goal is unlikely for older patients with
      diagnoses other than localized head and neck cancer.

PMID- 15854180
TI  - The safety of pegylated interferon alpha-2b in the treatment of chronic hepatitis
      B: predictive factors for dose reduction and treatment discontinuation.
AB  - BACKGROUND: Treatment with interferon-alpha has been shown to be effective in one
      third of hepatitis B e antigen-positive chronic hepatitis B patients, but is
      clinically associated with relevant adverse events. AIM: To investigate the
      safety of pegylated interferon alpha-2b in 300 hepatitis B e antigen-positive
      patients with compensated liver disease. METHODS: Patients were treated with
      pegylated interferon alpha-2b for 52 weeks combined with either lamivudine 100
      mg/day or placebo. Pegylated interferon alpha-2b was administered for 100 microg
      once a week for 32 weeks; thereafter, the dose was reduced to 50 microg once a
      week. Adverse events and their effect on study medication were reported at
      monthly visits in a standardized way. RESULTS: The most frequently reported side
      effects were flu-like syndrome (68%), headache (40%), fatigue (39%), myalgia
      (29%) and local reaction at the injection site (29%). These symptoms typically
      occurred within the first month of therapy and subsided during the course of
      therapy. Neutropenia and thrombocytopenia induced by pegylated interferon alpha
      2b increased the risk of infections and bleeding complications, but these
      complications were rare and mild. The frequency of all side-effects was not
      different between patients treated with pegylated interferon alpha-2b combined
      with lamivudine or placebo. In 69 (22%) patients the dose of pegylated interferon
      alpha-2b was reduced prematurely. Of these dose reductions, 36 (52%) were because
      of neutropenia. Therapy was discontinued in 28 (8%) patients. The most frequent
      reasons for early discontinuation were psychiatric side-effects (depression,
      psychosis) and flu-like symptoms. Multivariate Cox regression analysis showed
      that low neutrophil count at baseline and cirrhosis were independent predictors
      of dose reduction or therapy discontinuation. CONCLUSION: We conclude that in
      patients with chronic hepatitis B and compensated liver disease prolonged
      pegylated interferon alpha-2b therapy is safe, and that pre-existent cirrhosis
      and neutropenia are the most important predictors of dose reduction or early
      treatment discontinuation.

PMID- 15854183
TI  - Generic prescribing--cost saving chaos.

PMID- 15854181
TI  - Impact of liver steatosis on virological response in [corrected] Italian patients
      with chronic hepatitis C treated with peg-interferon alpha-2b plus ribavarin.
AB  - BACKGROUND: Whether liver steatosis affects sustained virological response in
      patients with chronic hepatitis C is still under discussion. AIM: To evaluate the
      impact of liver steatosis in patients treated (for chronic hepatitis C) with
      combination therapy. METHODS: We evaluated 97 (male/female 82/15, mean age 41.1
      years) consecutive naive patients treated with pegylated interferon alpha-2b plus
      ribavirin. RESULTS: Prevalence and severity of liver steatosis were significantly
      associated with genotype 3a [grade 3-4 in 14 of 32 patients (44%) vs. 8 of 65
      patients (12%) with other genotypes; P = 0.001], while steatosis grade 1 (<10% of
      hepatocytes affected) was more frequently associated with genotype 1a/1b [9/39
      (23%) vs. 4/57 (7%); P = 0.02]. Overall, sustained virological response was
      62.8%, and was statistically uninfluenced by the presence/absence of liver
      steatosis. On the contrary, the following variables were independently associated
      with sustained virological response at logistic regression analysis: genotype
      other than 1a/1b, positive association, (odds ratio 3.4, P < 0.04), and low-grade
      liver steatosis, negative association, (odds ratio 9.0, P = 0.009), whereas
      sustained virological response was unaffected by severe liver steatosis, which
      was mainly associated with genotypes 2 and 3 [steatosis grade 2, 18/29 (62%);
      grade 3, 10/12 (83%); grade 4, 7/10 (70%)]. CONCLUSIONS: Only low-grade liver
      steatosis negatively affects the outcome of combination therapy, with
      peginterferon alpha-2b plus ribavirin, while severe steatosis (which is virus
      related in most cases) has no impact on virological response.

PMID- 15854184
TI  - The new vaccines in the UK: chaos or progress?

PMID- 15854185
TI  - Laparoscopic nephrectomy: the new gold standard?
AB  - Laparoscopic nephrectomy has lesser blood loss, quicker recovery and return to
      work, shorter hospital stay, lesser post operative pain and analgesia requirement
      associated with it compared to open nephrectomy along with having oncological
      equivalence to open nephrectomy for T1, T2 renal tumours and for level 1 renal
      vein invasion by tumour thrombus. It has assumed the status of the New Gold
      Standard.

PMID- 15854186
TI  - Cophenylcaine spray vs. placebo in flexible nasendoscopy: a prospective double
      blind randomised controlled trial.
AB  - Practices vary across the UK on the use of topical preparation prior to flexible
      fibreoptic nasendoscopy. In this double-blind study, we randomised 98 patients to
      receive cophenylcaine or placebo nasal spray before flexible nasendoscopy. A
      visual analogue scale (1-100) was used to record pain, unpleasantness of taste
      and overall discomfort experienced. Overall, the procedure was associated with
      minimal pain and discomfort in both groups. There was no significant difference
      in pain or overall discomfort experienced between the two groups; however, the
      sensation of bad taste was significantly worse in the cophenylcaine group. In
      linear regression, factors that predicted the overall unpleasantness of the
      experience were primarily pain experienced and secondarily unpleasantness of
      taste. We conclude that the routine use of cophenylcaine for nasal preparation is
      not justified before flexible nasendoscopy.

PMID- 15854187
TI  - Pioglitazone in a subgroup of patients with type 2 diabetes meeting the criteria
      for metabolic syndrome.
AB  - Pioglitazone monotherapy and combinations were assessed in patients with type 2
      diabetes and metabolic syndrome (Adult Treatment Panel III criteria) from four
      worldwide randomised, multicentre, double-blind studies. Patients were treated
      for 52 weeks with pioglitazone (PIO, n = 1040), sulphonylurea (SU, n = 535) or
      metformin (MET, n = 500) PIO + SU (n = 277) or MET + SU (n = 273); or PIO + MET
      (n = 286) or SU + MET (n = 275). Pooled week 52 glycaemic and lipid changes were
      compared using analysis of covariance. Haemoglobin A(1c) decreased significantly
      with pioglitazone compared with sulphonylurea (p < 0.05). Fasting, 2- and 3-h
      plasma glucose, insulin and homeostasis model assessment for insulin resistance
      decreased significantly with pioglitazone compared with other monotherapies (p <
      0.05) and decreased significantly with PIO + MET compared with SU + MET (p <
      0.05). Pioglitazone, alone and with metformin, improved lipid components of
      diabetic dyslipidaemia more than did their respective comparison groups.
      Pioglitazone was associated with weight increase. In conclusion, pioglitazone
      provided effective glycaemic control and lipid profile improvements in patients
      with type 2 diabetes and metabolic syndrome.

PMID- 15854188
TI  - A 6-month study of the efficacy and safety of tadalafil in the treatment of
      erectile dysfunction: a randomised, double-blind, parallel-group, placebo
      controlled study in Australian men.
AB  - The efficacy and safety of tadalafil for the treatment of erectile dysfunction
      (ED) were assessed in a 6-month, randomised, double-blind, placebo-controlled
      study. Australian men with mild, moderate or severe ED of organic, psychogenic or
      mixed aetiology were randomised to tadalafil 20 mg as needed (n = 93) or placebo
      (n = 47). Efficacy assessments included the international index of erectile
      function (IIEF) and the sexual encounter profile (SEP) diary. Tadalafil
      significantly improved erectile function compared with placebo (p < 0.001, all
      measures). At the end of the study, the mean per-patient proportion of successful
      sexual intercourse attempts (SEP question three) was 73.5% for patients treated
      with tadalafil and 26.8% for placebo-treated patients. Improved erections were
      reported by 78% of tadalafil-treated patients compared to 12.8% of placebo
      treated patients. The most common treatment-emergent adverse events--headache and
      dyspepsia--were generally mild or moderate. Tadalafil was effective and well
      tolerated in Australian men with mild to severe ED.

PMID- 15854189
TI  - Lipoprotein(a) levels in patients with unstable angina and their relationship
      with atherothrombosis and myocardial damage.
AB  - The aim of the study was to compare lipoprotein(a) [Lp(a)] levels in patients
      with cTroponin-I (cTn-I)-positive or -negative unstable angina and to investigate
      their relationship with atherothrombosis. A total of 202 consecutive patients
      were enrolled in the study. Lp(a), fibrinogen, plasminogen, PAI-1 and t-PA levels
      were measured and C-reactive protein (CRP) assays were performed on admission for
      all patients, and venous blood samples were drawn 12 and 24 h later for cTn-I
      measurements. The patients were divided into cTn-I-negative (cTn-I < 1 ng/ml) and
      -positive (cTn-I > or = 1 ng/ml) unstable angina groups. Lp(a) levels of the cTn
      I-positive patients were higher than those of the cTn-I-negative patients (52.9
      +/- 6.0 and 15.7 +/- 2.5 mg/dl, p < 0.0001). There was a positive correlation
      between Lp(a) and cTn-I levels (r = 0.692; p = 0.0001). Increase in coagulation
      activity and impairment in fibrinolytic activity were significant in the cTn-I
      positive patients. Elevated Lp(a) levels may have a role in the development of
      myocardial damage in patients with unstable angina.

PMID- 15854190
TI  - Short-acting beta 2-agonist and oral corticosteroid use in asthma patients
      prescribed either concurrent beclomethasone and long-acting beta 2-agonist or
      salmeterol/fluticasone propionate combination.
AB  - Prescriptions for short-acting beta(2)-agonists (SABAs) and oral corticosteroids
      recorded in a primary care database were used as markers of asthma control. Drug
      use in the 6 months before and after step-up in treatment from inhaled
      corticosteroids [ICs; total daily dosage of < or =1000 microg beclomethasone
      dipropionate (BDP) or equivalent] to either salmeterol/fluticasone propionate
      combination (SFC) or concurrent BDP and long-acting beta(2)-agonists (LABAs)
      given in separate inhalers was compared. After step-up, the calculated median
      number of doses of SABAs prescribed fell by 100 in the SFC group (n = 211) but
      was unchanged with BDP + LABA (n = 377, p < 0.0001), and fewer patients in the
      SFC group were prescribed oral corticosteroids (13.7 vs. 20.7%, p = 0.036). Other
      measures of SABA use after step-up indicated lower use in the SFC group. In
      clinical practice, adding LABA to IC therapy by using a combination inhaler
      produces significantly better asthma control than administering the drugs in
      separate inhalers.

PMID- 15854191
TI  - Pulmonary function studies in Kuwaiti children with sickle cell disease and
      elevated Hb F.
AB  - Conflicting ventilatory defects have been reported in children with sickle cell
      disease (SCD). In Kuwait, the disease is relatively mild with a low incidence of
      acute chest syndrome and other complications, presumably due to the Arab-Indian
      haplotype chromosomal background and elevated Hb F levels. There have been no
      previous studies of pulmonary function in patients with this haplotype. Pulmonary
      function test (PFT) was carried out on 28 steady state children with SCD (21
      homozygous sickle cell (SS), seven S beta(o) thal) and two group of controls: 17
      age- and sex-matched healthy children and 10 children with HbH disease. The
      charts of the SCD patients were reviewed for frequency of acute chest syndrome
      and vaso-occlusive crisis. The mean values of forced vital capacity (FVC) (83.2
      +/- 11.9 vs. 91.2 +/- 11.7) and vital capacity (VC) (81.5 +/- 11.8 vs. 90.5 +/-
      10.9) were significantly lower in the SS patients compared with healthy controls
      (p < 0.05). Similarly, these values were significantly lower than in those of the
      HbH group (p < 0.001 for VC and p < 0.01 for FVC). The mean forced expiratory
      volume in 1 s (FEV1) was lower in SS patients (86.4 +/- 11.5) compared with
      healthy controls (94.2 +/- 14.2), but the difference was not significant (p =
      0.07). Also, the FEV1 was significantly lower in SS patients than in the HbH
      group (p < 0.001). There was no significant difference in the PFT parameters
      between SS patients with acute chest syndrome and those without. Although
      patients with frequent vaso-occlusive crisis had lower PFT parameters, the
      differences were not significant in comparison to those with infrequent crisis.
      This study revealed an early restrictive and obstructive pulmonary function
      pattern in steady state children with SCD. The finding also indicates that the
      changes of PFT parameters in SS patients could not be attributed to anaemia per
      se as patients with HbH who also have chronic anaemia did not show similar
      changes. This observation underscores the early occurrence of pulmonary
      involvement, even in patients with an otherwise relatively mild SCD.

PMID- 15854192
TI  - Surgical approach of pulmonary hydatidosis in childhood.
AB  - To review the results of different surgical treatment in hydatid disease of the
      lung in paediatric patients. A total of 102 children with pulmonary hydatid cysts
      were treated at the our clinic in the period from 1990 to 2001. There were 59
      boys and 43 girls and their age ranged from 4 to 16 years (mean 10.2). Chest
      radiography, computed tomography and abdominal ultrasonography were the most
      commonly used diagnostic techniques. The cysts were located in the right lung in
      68 patients (66.6%), in the left lung in 30 patients (29.4%), in both lungs in
      four patients (3.9%). Concomitant liver cyst hydatid was also detected in 12
      patients that were located at right lung, and two patients with bilateral lung
      involvement. All cases were managed surgically. Of 14 cases with concomitant
      liver and intrathoracic hydatid cysts, right thoracophrenotomy was performed in
      12, median sternotomy in one, and phrenotomy in other. Partial cystectomy and
      capitonnage were the most commonly used surgical methods. Post-operative
      complication was seen in 10 (9.8%) patients. Infection at the incision site
      occurred in four patients and air leakage in three. Complications of capitonnage
      were seen in three patients. One patient (1%) died at fourth post-operative day
      due to sepsis. Parenchyma protective operations should be performed especially in
      children living in endemic areas because of the possibility of recurrence of the
      disease in the future. Single stage operations in suitable cases decrease the
      cost of treatment and make surgical therapy suitable in both children and young
      adults, by reducing the hospital in-patient time and morbidity.

PMID- 15854193
TI  - Neck pain and disability: a cross-sectional survey of the demographic and
      clinical characteristics of neck pain seen in a rheumatology clinic.
AB  - This hospital-based cross-sectional cohort study examines the clinical and
      demographic features of neck pain, disability (using the Northwick Park neck pain
      questionnaire) and relationships to handicap in employment. Of 173 consecutive
      referrals to a rheumatology clinic with neck pain, 70% had neck/arm pain without
      neurological involvement, 13% other conditions, 11% nerve involvement and 5%
      other spinal pain. 141 patients (mean age 50 years) had mechanical or
      degenerative neck pain, of which 13% was probably work-related and 13% was trauma
      related. 44 had taken sickness absence for an average of 30 weeks. Comorbidities
      were frequent (lumbar pain 51%). Those in work were significantly less disabled
      than those not working (p = 0.001) and those off sick (p < 0.01). Those reporting
      sleep disturbance, tearfulness and crying were significantly more disabled (p =
      0.0001) than those who did not. Neck pain in secondary care is complicated by
      physical and emotional comorbidities. Comprehensive management requires a
      biopsychosocial model of care.

PMID- 15854194
TI  - Characteristics of patients with late onset systemic lupus erythematosus in
      Turkey.
AB  - Systemic lupus erythematosus (SLE) is a multi-system autoimmune disorder mainly
      affecting young women. In this study, we aimed at investigating the clinical,
      laboratory and management characteristics of our SLE patients with an age of
      onset > or =50. Twenty patients with late onset SLE (> or =50 years) were
      identified from the records, on the basis of their first SLE-related symptoms
      (Group I). A hundred consecutive SLE patients with initial symptoms before the
      age of 50 were also selected as controls (Group II). Clinical, laboratory and
      management characteristics of the patients were recorded according to pre-defined
      protocol and compared by chi(2), Student's t-test and Fisher's exact test.
      Comparison of the demographic findings between the Group I (F/M: 18/2) and the
      Group II (F/M: 90/10) were as follows: the mean age of disease onset was 53.9 +/-
      4.5 years vs. 26.3 +/- 9.2 years, mean time of follow-up was 44.2 +/- 40.5 months
      vs. 50.1 +/- 47.4 months, mean damage index was 0.6 +/- 0.6 vs. 0.58 +/- 1.4.
      There was no significant difference between the two groups with regard to
      clinical, laboratory parameters, damage index and immunosuppressive treatment
      characteristics. SLE-related manifestations were similar in two groups except
      fever (10% in the Group I vs. 41% in the Group II; p = 0.01). The only two
      patients with pulmonary fibrosis were found in the Group I (p = 0.027). The
      clinical and laboratory characteristics and the disease outcome in SLE patients
      with an age of onset > or =50 years did not show significant differences from the
      control SLE patients with a younger age of onset.

PMID- 15854195
TI  - Renal involvement in patients with polymyositis and dermatomyositis.
AB  - Renal involvement in patients with polymyositis (PM)/dermatomyositis (DM) is
      previously thought to be uncommon, but two main types of renal lesion have been
      described. First, acute tubular necrosis with renal failure related to
      myoglobulinemia and myoglobulinuria is a well-recognised feature of acute
      rhabdomyolysis. Second, chronic glomerulonephritis has been infrequently reported
      in a small group of patients with PM/DM. This study aims at investigating the
      incidence, severity and prognosis of renal disease in PM/DM patients, admitted to
      a single centre in a 10-year interval. The hospital records of 65 Taiwanese
      patients with PM/DM, examined between 1992 and 2002, were studied
      retrospectively. Of the 65 patients, 14 were found to have suffered varying
      degree of renal involvement, and the incidence rate was 21.5%. All the 14
      patients had varying degree of haematuria and proteinuria. Acute tubular necrosis
      with renal failure developed in four patients with PM and in five patients with
      DM. Renal biopsy in two DM patients with overt proteinuria revealed IgA
      nephropathy in one and membranous nephropathy in the other. We, therefore,
      concluded that renal involvement in PM/DM patients is not as uncommon as
      previously thought.

PMID- 15854196
TI  - Dyspepsia management in primary care: a management trial.
AB  - The aim was to evaluate the outcomes associated with four initial management
      strategies in new patients presenting to primary care physicians with dyspepsia.
      Patients with new symptoms (no alarm features) were randomised to empirical
      therapy (n = 11), Helicobacter pylori (HP) serology (n = 8), HP breath testing (n
      = 11) or oesophagogastroduodenoscopy (n = 13). Dyspepsia and health-related
      quality of life were assessed using standardised questionnaires at entry, 6 and
      24 weeks post-trial enrollment. Outcomes were assessed by structured telephone
      interview every 6 weeks. In the initial HP testing arms, 21% were positive; 27%
      in the oesophagogastroduodenoscopy arm had inflammatory changes without ulcers at
      baseline. The majority (67%) received over the counter medication after initial
      management. Symptom-free status was similarly common in all groups (p = 0.49);
      only 20% pursued further evaluation. Total billed charges were higher in the
      oesophagogastroduodenoscopy group (US 2077 dollars) vs. empirical therapy (US 512
      dollars), despite excluding the charge for initial oesophagogastroduodenoscopy,
      but overall, no effects on total medical charges were detected (p = 0.10).
      Regardless of initial management, most patients remained symptomatic, yet did not
      return for health care visits or undergo endoscopies. The cost of upfront
      endoscopy may not be the best choice for patients presenting with new dyspepsia.

PMID- 15854197
TI  - Characteristics of patients with adult-onset familial Mediterranean fever in
      Turkey: analysis of 401 cases.
AB  - It has been generally accepted that the clinical onset of familial Mediterranean
      fever (FMF) begins before 20 years of age in most patients. In this study, we
      aimed to investigate the demographic and clinical characteristics of our FMF
      patients with an age of onset > or =20. Records of 401 patients (female/male:
      204/197) that followed up between 1990 and 1999 were reviewed according to a pre
      defined protocol. All patients fulfilled the diagnostic criteria of Livneh et al.
      The demographic and clinical features of adult-onset FMF patients were compared
      to those of patients with a disease onset before 20 years of age. There were 57
      patients (14%) who experienced symptoms of FMF at > or =20 years of age; 34 of
      them (8.5%) reported their first attack between 20 and 29 years of age; 18 of
      them (4.5%) between 30 and 39 years of age and five patients (1.25%) had their
      first attack after 40 years of age. Arthritis (42 vs. 65%, p = 0.001) and
      erysipelas-like erythema (7 vs. 17%, p = 0.047) were significantly less frequent
      in patients with adult-onset FMF compared to patients with disease onset before
      20 years of age. Arthritis and erysipelas-like erythema were less frequent in
      adult-onset patients compared to those with an earlier disease onset. Adult-onset
      FMF may be a form of disease with distinct clinical, demographic and molecular
      characteristics. Prospective clinical studies and investigation of genotypic
      features are needed to identify the characteristics of this phenotypic variant.

PMID- 15854198
TI  - Frequency of hepatitis G virus and transfusion-transmitted virus infection in
      type II diabetes mellitus.
AB  - The hepatitis G virus (HGV) and transfusion-transmitted virus (TTV) are recently
      defined hepatitis viruses that the pathogenic roles in liver diseases are still
      not clear. It has been well known that some hepatitis virus, such as hepatitis C,
      might have an affinity to pancreatic islet cells. To investigate the relationship
      between the newly defined hepatitis viruses and diabetes mellitus (DM), we
      studied the prevalence of TTV and HGV in a type 2 diabetic patient population.
      Serum samples of 60 patients with DM and 45 healthy volunteers as control were
      taken. HGV RNA and TTV DNA was investigated by polymerase chain reaction. HGV was
      detected in none of diabetic patients (0%) and only one in control group (2.2%).
      However, TTV DNA was detected in 16 patients with DM (26%) and in five controls
      (11%). TTV was more prevalent in diabetic patients, but the difference between
      groups was not statistically significant (p > 0.05). These results revealed that
      TTV is more common in diabetic patients than in controls. At present, we don't
      know if this result is only a coincidence or a sign of potential association
      between TTV and DM. Further studies are certainly needed to elucidate a potential
      relationship.

PMID- 15854199
TI  - Predisposing factors and clinical symptoms in HIV-negative patients with Candida
      oesophagitis: are they always present?
AB  - Candida oesophagitis (CO) is scarce among immunocompetent patients. This study
      aimed at evaluating predisposing factors, clinical symptoms and endoscopic
      findings in this group. We retrospectively reviewed 55 patients diagnosed as CO
      endoscopically (whitish plaques) and cytologically (fungal mycelia on brush
      cytology). Carcinoma, diabetes, acid suppression, steroids, gastric surgery and
      oesophageal motility disorders were considered as predisposing factors. Twenty of
      55 patients lacked any predisposing factor for CO. These patients were more
      frequently asymptomatic (8/20) when compared with those with known predisposing
      factors (5/35) (p = 0.031). Moreover, dysphagia was more prevalent in the latter
      group (24/35 vs. 8/20; p = 0.039). Endoscopic findings correlated with the
      presence of neither predisposing factors nor symptoms (Wilcoxon p > 0.05). Thus,
      CO can be discovered in patients without apparent predisposing risk factors and
      clinical symptoms. Further studies are needed to elucidate the mechanisms of
      transition from colonisation to infection.

PMID- 15854200
TI  - Redefining efficacy of antihypertensive therapies beyond blood pressure reduction
      -the role of angiotensin II antagonists.
AB  - Antihypertensive efficacy must be redefined beyond blood pressure (BP) lowering
      per se to include reducing the cardiovascular complications of hypertension.
      Treatment decisions should be based on results from large clinical trials with
      relevant clinical outcomes. Several recent morbidity and mortality trials with
      angiotensin II receptor antagonists (AIIAs) provide an evidence-based rationale
      for the use of AIIAs in patients with hypertension. Studies with AIIAs in
      comparison to conventional antihypertensive agents showed improved morbidity and
      mortality outcomes in patients with hypertension and left ventricular hypertrophy
      (losartan) and diabetes mellitus (losartan and irbesartan). Trials with some
      members of the AIIA class (candesartan and valsartan) have not demonstrated such
      benefits in comparison to conventional agents, possibly due to differences in BP
      control during the trials. The results of these AIIA outcome trials have impacted
      on recently issued clinical guidelines for management of hypertension.

PMID- 15854201
TI  - Endothelial dysfunction links erectile dysfunction to heart disease.
AB  - Erectile dysfunction (ED) and coronary artery disease (CAD) overlap in risk
      factors, aetiology and clinical outcomes. It has become clear that ED is an
      important marker of vascular disease throughout the arterial tree--including CAD,
      stroke and diabetes. Epidemiological studies have demonstrated a close
      association between ED and vascular disease. The shared aetiological factor is
      endothelial dysfunction. The fact that ED tends to precede the onset of symptoms
      of other vascular diseases--because blood vessels in the penis are narrower in
      diameter than elsewhere in the body so blood flow is restricted sooner by
      atherosclerosis--means that it can be used as a 'window' on vascular health.
      There is growing evidence that patients presenting with ED should be investigated
      for cardiovascular disease (CVD), including diabetes, even if they have no
      symptoms. Early detection could facilitate prompt intervention and a reduction in
      long-term complications. Treatments that reduce endothelial dysfunction offer the
      potential of improving the functioning of the entire vascular system, improving
      outcomes in CVD and diabetes, as well as providing effective treatment for ED.

PMID- 15854202
TI  - Update on treatment guidelines for acute bacterial sinusitis.
AB  - Acute bacterial sinusitis (ABS) is a common complication of viral upper
      respiratory tract infections and represents a considerable social burden both in
      terms of diminished quality of life for the patient and the economic implications
      of decreased productivity and treatment costs. Several national health
      authorities have developed guidelines for the management of ABS, which aim to
      promote rational selection of anti-bacterial therapy to optimise clinical
      outcomes while minimising the potential for selection of anti-bacterial
      resistance as a result of inappropriate anti-bacterial usage. This article
      provides an overview of current guidelines, with particular focus on the clinical
      significance of variations in treatment recommendations and new treatment
      options, such as the ketolide telithromycin, which was recently added to a number
      of national treatment guidelines.

PMID- 15854203
TI  - Pitavastatin.
AB  - The growing number of trials that have highlighted the benefit of intensive
      lowering of total- and low density lipoprotein (LDL)-cholesterol levels
      especially with statins has created a need for more efficacious agents.
      Pitavastatin is a new synthetic 3-hydroxy-3-methyl glutaryl coenzyme A reductase
      inhibitor, which was developed, and has been available in Japan since July 2003.
      Metabolism of pitavastatin by the cytochrome P450 (CYP) system is minimal,
      principally through CYP 2C9, with little involvement of the CYP 3A4 isoenzyme,
      potentially reducing the risk of drug-drug interactions between pitavastatin and
      other drugs known to inhibit CYP enzymes. To date, human and animal studies have
      shown pitavastatin to be potentially as effective in lowering LDL-cholesterol
      levels as rosuvastatin; although, head-to-head studies are yet to be conducted.

PMID- 15854204
TI  - Hypertriglyceridaemia and malignancy.
AB  - Severe hypertriglyceridaemia is a rare presentation usually associated with acute
      pancreatitis. We present two case reports of severe hypertriglyceridaemia
      occurring in patients with previous autoimmune disease and haematological and
      solid malignancies but no evidence of prior or concurrent pancreatitis or
      hyperlipidaemia. These case reports illustrate that haematological and solid
      organ malignancies and autoimmunity may be relevant as exacerbating factors in
      the presentation of severe type IV or V hypertriglyceridaemia.

PMID- 15854205
TI  - The effect of consultant-led interactive pre-clinic case note review on follow-up
      rates of an otology outpatient clinic.
AB  - The effect of pre-clinic consultant-led interactive case note discussion on the
      follow-up rate of an otology outpatient clinic was assessed. The clinic was
      divided into two groups. In one group, all cases were delegated by the consultant
      at the beginning of clinic without discussion. In the other group, before the
      start of clinic, the team reviewed all case notes and formed a management plan
      for each patient. Overall, lower follow-up rates were observed in cases which
      were discussed prior to the start of clinic (53.2-45.7%; p = 0.02). This was
      found in all doctor grades, although statistically significant only for middle
      grade (consultant: 48.3-41.6%, p = 0.10; middle grade: 58.5-45.5%, p = 0.05 and
      senior house officer: 60.2-57.8%, p = 0.73). Junior doctor's follow-up rates were
      much higher than the consultant's rates (p < 0.01). In conclusion, pre-clinic
      consultant-led case note review reduced otology outpatient follow-up rate.

PMID- 15854206
TI  - Aseptic meningitis as initial presentation of rheumatic fever in an adult man: an
      extraordinary rare manifestation.

PMID- 15854209
TI  - Abstracts of the 38th Congress of the Japan Epilepsy Society, Shizuoka, Japan,
      September 30-October 1, 2004.

PMID- 15854210
TI  - Devices and the food and drug administration.

PMID- 15854211
TI  - Stem cell therapy as the reinforcement of organ regeneration.

PMID- 15854212
TI  - Right ventricular failure after left ventricular assist device implantation: the
      need for an implantable right ventricular assist device.
AB  - Right ventricular failure after implantation of a left ventricular assist device
      is an unremitting problem. Consideration of portal circulation is important for
      reversing liver dysfunction and preventing multiple organ failure after left
      ventricular assist device implantation. To achieve these objectives, it is
      imperative to maintain the central venous pressure as low as possible. A more
      positive application of right ventricular assistance is recommended. Implantable
      pulsatile left ventricular assist devices cannot be used as a right ventricular
      assist device because of their structure and device size. To improve future
      prospects, it is necessary to develop an implantable right ventricular assist
      device based on a rotary blood pump.

PMID- 15854213
TI  - Off-design considerations of the 50cc Penn State Ventricular Assist Device.
AB  - Particle image velocimetry is used to study the flow field associated with off
      design conditions of the 50cc Penn State Ventricular Assist Device. Phase average
      data, for 300 consecutive beats, was acquired for 60, 75, and 90 beats per minute
      (bpm) at 35/65 systolic duration and at 75 bpm for 50/50 systolic duration.
      Diastolic flow is dominated by the inflow jet and shows more penetration and
      better wall washing at higher beat rates and shorter diastolic time. A flow
      separation near the minor orifice of the aortic valve, however, is larger under
      these conditions. Turbulent energy, which peaks during diastole, is found to be
      strongest at the edges of the jet and near the valves and scales well with the
      maximum inlet jet velocity. A region of potential separation on the right lateral
      wall is identified and will be relieved by geometric modifications of the
      evolving design.

PMID- 15854214
TI  - Dynamic analysis of the resultant force acting on the hip joint during level
      walking.
AB  - The present study was designed to determine the resultant force acting on the hip
      joint during walking using a new dynamic analysis method. Our model utilized
      joint motion, ground reaction force, and muscle strength data from 18 women (6
      normal women aged 20-24 years, 6 normal women aged 50-57 years, and 6 female
      patients with osteoarthritis, aged 50-66 years). We analyzed the resultant force
      using the multibody dynamic analysis system. To determine the factors that
      influence the force acting on the hip, we examined the effect of age and total
      hip arthroplasty. The maximum resultant force acting on the femoral head was
      dependent on the subject body weight and correlated with muscle strength and
      walking speed. The results of this study highlight the agreement between computer
      simulation analysis and actual measurement of the resultant force acting on the
      hip. Our results suggest that muscle strength and walking speed are significant
      determinants of the resultant force acting on the hip.

PMID- 15854215
TI  - Potential predictive markers for proliferative capacity of cultured human
      articular chondrocytes: PCNA and p21.
AB  - The purpose of this study was to investigate age-related changes in the
      proliferative ability of human articular chondrocytes in culture. In addition,
      the possible markers for the proliferative capacity of chondrocytes were
      examined. Chondrocytes obtained from human articular cartilages of young (under
      40 years) or old (over 60 years) individuals were expanded until their growth was
      arrested. The number of cells and the type II collagen phenotype were determined
      together with the expression levels of proliferating cell nuclear antigen (PCNA)
      and p21(WAF1/CIP) along with the passages of cultured chondrocytes. The results
      showed that young chondrocytes had higher proliferative capacity and viability
      than old chondrocytes. The growth arrest and the cessation in the expression of
      type II collagen were accompanied by down-regulation of PCNA and up-regulation of
      p21(WAF1/CIP) levels in both young and old chondrocytes. Notably, the expression
      levels of PCNA and p21(WAF1/CIP) along with the passages were correlated
      inversely to each other and showed distinct patterns between young and old
      chondrocytes. These results suggest that senescence of human articular
      chondrocytes leads to the decrease in the proliferative capacity and phenotypic
      stability. In addition, PCNA and p21 could be molecular markers that represent
      the status of these age-related properties of human articular chondrocytes in
      vitro.

PMID- 15854216
TI  - Survival and complications of indwelling venous catheters for permanent use in
      hemodialysis patients.
AB  - BACKGROUND: The risk factors influencing the survival of indwelling central vein
      catheters and their potential complications have not been assessed in depth and
      on a large scale. METHODS: We investigated the general characteristics of 245
      single lumen cuffed tunneled catheters and analyzed their survival by Kaplan
      Meier and Cox regression analysis. Risk factors for bacteremia and thrombosis
      were assessed by logistic regression analysis. RESULTS: The incidence of exit
      site infection, tunnel infection, bacteremia and thrombotic events was 0.35,
      0.25, 1.71, and 1.94/1000 catheter days, respectively. The mean survival time per
      catheter was 276 days. After censoring for non catheter-related events leading to
      the removal of the catheter (n = 245 with 120 catheters censored and 125 events),
      the mean survival time of the catheter appeared to be 615 +/- 67 days (95% CI of
      483-747) and the median survival time 310 +/- 50 days (95% CI of 212-408). The
      localization of the catheter into the right internal jugular vein results in
      significantly better survival as compared with other insertion sites both in
      Kaplan-Meier (mean survival of 650 days compared to a mean survival of 519 days,
      P value < 0.009) and in Cox regression analysis (relative risk of 0.537, P value
      < 0.001). Localization of the catheter into the right internal jugular vein
      seemed to increase the risk for bacteremia (relative risk of 1.798, P value of
      0.063). The use of anticoagulant agents was not protective for thrombosis,
      although this might be due to lack of power (relative risk of 0.626, P value of
      0.141). CONCLUSION: We provide evidence of a mean survival in long-term
      hemodialysis catheter close to 2 years with an acceptable complication rate. If a
      long-term hemodialysis catheter is required, it is best placed in the right
      internal jugular vein.

PMID- 15854217
TI  - On-line hemodiafiltration does not induce inflammatory response in end-stage
      renal disease patients: results from a multicenter cross-over study.
AB  - BACKGROUND: On-line hemodiafiltration (HDF) represents the supreme blood
      purification modality for end-stage renal disease (ESRD) patients. Large-volume
      infusion of on-line prepared substitution fluid may, however, expose patients to
      inflammatory contaminants. As a result, on-line HDF might aggravate chronic
      inflammation, which correlates with malnutrition, cardiovascular disease, and
      mortality among ESRD patients. METHODS: In a multicenter cross-over study, 27
      ESRD patients were randomly assigned to treatment with on-line HDF and low-flux
      hemodialysis (HD). After 6 months, patients were crossed to the other treatment
      modality, and treatment continued for another 6 months. Both on-line HDF and low
      flux HD were conducted with polysulfone membranes and ultrapure dialysis fluid.
      Samples were drawn at the end of each treatment period. RESULTS: Inflammatory
      parameters were elevated in the study population when compared to healthy
      controls. Induction of interleukin-1 receptor antagonist (IL-1Ra) and tumor
      necrosis factor alpha (TNF-alpha) was comparable for on-line HDF and low-flux HD,
      and there was no intradialytic increase in cytokine production. As a result,
      interleukin-6 (IL-6) plasma levels did not differ significantly between the two
      treatment modalities. Similarly, no difference between on-line HDF and low-flux
      HD was observed for C-reactive protein (CRP) and albumin. Markers of endothelial
      cell activation (soluble intercellular and vascular cell adhesion molecules sICAM
      1 and sVCAM-1) as well as the cardiovascular risk marker cardiac troponin T
      (cTnT) remained elevated compared to healthy subjects, but showed no difference
      between the two treatment modalities. CONCLUSIONS: On-line HDF, as the most
      effective renal replacement therapy, does not provoke inflammatory response and
      is both safe and highly biocompatible.

PMID- 15854218
TI  - Changes in conjugated linoleic acid and palmitoleic acid are correlated to
      retinol levels in chronic renal failure in both hemodialysis and conservative
      treatment patients.
AB  - An increase in conjugated linoleic acid (CLA), a natural fatty acid present in
      our diet, which possesses anticarcinogenic and antiatherogenic activities in
      experimental models, has been found in both the plasma and adipose tissue of end
      stage chronic renal failure (ESCRF) patients. Increased levels of retinol have
      also been found in those patients, due to a reduced excretion of the retinol
      binding protein. Since retinol is known to influence lipid metabolism, we
      evaluated whether changes in retinol, CLA, and other fatty acids are correlated
      in the plasma of CRF patients. We measured CLA, retinol, and unsaturated fatty
      acids in the plasma of the following groups: (A) 35 ESCRF patients; (B) 20
      hemodialysis (HD) patients; (C) 20 healthy controls. Subjects with total
      cholesterol and/or triglycerides higher than 250 mg/dL were excluded. We found a
      significant increase in CLA, retinol, palmitoleic (16:1), and oleic (18:1) acids
      in ESCRF patients. In HD patients we found a similar pattern, however, CLA
      increase was not significant. No changes were observed in the other fatty acids
      measured. In the groups of ESCRF and HD patients, a positive correlation between
      the levels of plasma retinol and CLA, and between retinol and 16:1 was found.
      These correlations were not detected in controls. The abnormal levels of plasma
      retinol in CRF patients might partly explain the changes in CLA and 16:1. The
      influence of retinol levels on these fatty acids might be due to an induction of
      delta 9 desaturase. In fact, 16:1 is known to be produced, partly, by delta 9
      desaturation of palmitic acid. Moreover, the formation of CLA from delta 9
      desaturation of vaccenic acid-a trans-monounsaturated fatty acid present in our
      diet-has recently been demonstrated in humans. Nevertheless, our data do not
      represent direct evidence supporting an increased delta 9 desaturase activity in
      CRF patients. Another possible explanation might be a variation in the exogenous
      intake.

PMID- 15854219
TI  - Characterization of a hollow fiber bioartificial liver device.
AB  - A three-compartment bioartificial liver (BAL) has been developed for potential
      treatment of fulminant hepatic failure. It has been shown previously that
      viability and liver-specific functions were maintained in laboratory-scale
      bioreactors of such design. In this study, the performance of hepatocytes in a
      clinical-scale bioartificial liver was verified by sustained specific production
      rates of albumin and urea, along with oxygen consumption rates for up to 56 h and
      liver-specific gene expression for up to 72 h. In addition, transmission of
      porcine endogenous retrovirus and other type C retroviral particles across the
      hollow fibers was not detected under both normal and extreme operating fluxes.
      These results demonstrate that the clinical-scale BAL performs at a level similar
      to the laboratory scale and that it offers a viral barrier against porcine
      retroviruses.

PMID- 15854220
TI  - Development and characterization of a new stationary phase for an
      immunoadsorption wall.
AB  - This study introduces a newly developed method for the formation of a stationary
      phase superficially embedded with immunoadsorbent, that is partially incomplete
      two-stage polymerization of acrylamide. Preliminary experimental studies show
      that binding activity of the immunoadsorbent was satisfactorily maintained after
      immobilization. With an appropriate configuration of selected immunoadsorption
      matrices and immunoisolation barriers, it is hoped that this stationary phase
      could be used to resolve some difficult problems arising from the accumulation of
      certain middle molecular weight toxins not removed by other blood purification
      procedures.

PMID- 15854221
TI  - Sensori-motor adaptation to knee osteoarthritis during stepping-down before and
      after total knee replacement.
AB  - BACKGROUND: Stepping-down is preceded by a shift of the center of mass towards
      the supporting side and forward. The ability to control both balance and lower
      limb movement was investigated in knee osteoarthritis patients before and after
      surgery. It was hypothesized that pain rather than knee joint mobility affects
      the coordination between balance and movement control. METHODS: The experiment
      was performed with 25 adult individuals. Eleven were osteoarthritic patients with
      damage restricted to one lower limb (8 right leg and 3 left leg). Subjects were
      recruited within two weeks before total knee replacement by the same orthopedic
      surgeon using the same prosthesis and technics of surgery. Osteoarthritic
      patients were tested before total knee replacement (pre-surgery session) and
      then, 9 of the 11 patients were tested one year after the surgery when re
      educative training was completed (post-surgery session). 14 adult individuals
      (men: n = 7 and women: n = 7) were tested as the control group. RESULTS: The way
      in which the center of mass shift forward and toward the supporting side is
      initiated (timing and amplitude) did not vary within patients before and after
      surgery. In addition knee joint range of motion of the leading leg remained close
      to normal before and after surgery. However, the relative timing between both
      postural and movement phases was modified for the osteoarthritis supporting leg
      (unusual strategy for stepping-down) before surgery. The "coordinated" control of
      balance and movement turned to be a "sequential" mode of control; once the body
      weight transfer has been completed, the movement onset is triggered. This
      strategy could be aimed at shortening the duration-time supporting on the painful
      limb. However no such compensatory response was observed. CONCLUSION: The change
      in the strategy used when supporting on the arthritis and painful limb could
      result from the action of nociceptors that lead to increased proprioceptor
      thresholds, thus gating the proprioceptive inputs that may be the critical
      afferents in controlling the timing of the coordination between balance and
      movement initiation control.

PMID- 15854222
TI  - Promiscuous drugs compared to selective drugs (promiscuity can be a virtue).
AB  - BACKGROUND: The word selectivity describes a drug's ability to affect a
      particular cell population in preference to others. As part of the current state
      of art in the search for new therapeutic agents, the property of selectivity is a
      mode of action thought to have a high degree of desirability. Consequently there
      is a growing activity in this area of research. Selectivity is generally a worthy
      property in a drug because a drug having high selectivity may have a dramatic
      effect when there is a single agent that can be targeted against the appropriate
      molecular-driver involved in the pathogenesis of a disease. An example is chronic
      myeloid leukemia (CML). CML has a specific chromosomal abnormality, the
      Philadelphia chromosome, that results in a single gene that produces an abnormal
      protein. DISCUSSION: There is a burgeoning understanding of the cellular
      mechanisms that control the etiology and pathogeneses of diseases. This
      understanding both enables and motivates the development of drugs that induce a
      specific action in a selected cell population; i.e., a targeted treatment.
      Consequently, drugs that can target distinct molecular targets involved in
      pathologic/pathogenetic processes, or signal-transduction pathways, are being
      developed. However, in most cases, diseases involve multiple abnormalities. A
      disease may be associated with more than one dysfunctional protein and these may
      be out-of-balance with each other. Likewise a drug might strongly target a
      protein that shares a similar active domain with other proteins. A drug may also
      target pleiotropic cytokines, or other proteins that have multi-physiological
      functions. In this way multiple normal cellular pathways can be simultaneously
      influenced. Long term experience with drugs supposedly designed for only a single
      target, but which unavoidably involve other functional effects, is uncovering the
      fact that molecular targeting is not medically flawless. SUMMARY: We contend that
      an ideal drug may be one whose efficacy is based not on the inhibition of a
      single target, but rather on the rebalancing of the several proteins or events,
      that contribute to the etiology, pathogeneses, and progression of diseases, i.e.,
      in effect a promiscuous drug. Ideally, if this could be done at minimum drug
      concentration, side effects could be minimized. Corollaries to this argument are
      that the growing fervor for researching truly selective drugs may be imprudent
      when considering the totality of responses; and that the expensive screening
      techniques used to discover these, may be both medically and financially
      inefficient.

PMID- 15854223
TI  - Investigating hookworm genomes by comparative analysis of two Ancylostoma
      species.
AB  - BACKGROUND: Hookworms, infecting over one billion people, are the mostly closely
      related major human parasites to the model nematode Caenorhabditis elegans.
      Applying genomics techniques to these species, we analyzed 3,840 and 3,149 genes
      from Ancylostoma caninum and A. ceylanicum. RESULTS: Transcripts originated from
      libraries representing infective L3 larva, stimulated L3, arrested L3, and
      adults. Most genes are represented in single stages including abundant
      transcripts like hsp-20 in infective L3 and vit-3 in adults. Over 80% of the
      genes have homologs in C. elegans, and nearly 30% of these were with observable
      RNA interference phenotypes. Homologies were identified to nematode-specific and
      clade V specific gene families. To study the evolution of hookworm genes, 574 A.
      caninum/A. ceylanicum orthologs were identified, all of which were found to be
      under purifying selection with distribution ratios of nonsynonymous to synonymous
      amino acid substitutions similar to that reported for C. elegans/C. briggsae
      orthologs. The phylogenetic distance between A. caninum and A. ceylanicum is
      almost identical to that for C. elegans/C. briggsae. CONCLUSION: The genes
      discovered should substantially accelerate research toward better understanding
      of the parasites' basic biology as well as new therapies including vaccines and
      novel anthelmintics.

PMID- 15854224
TI  - Introducing the National Library for Health Skin Conditions Specialist Library.
AB  - BACKGROUND: This paper introduces the new National Library for Health Skin
      Conditions Specialist Library http://www.library.nhs.uk/skin. DESCRIPTION: The
      aims, scope and audience of the new NLH Skin Conditions Specialist Library, and
      the composition and functions of its core Project Team, Editorial Team and
      Stakeholders Group are described. The Library's collection building strategy,
      resource and information types, editorial policies, quality checklist, taxonomy
      for content indexing, organisation and navigation, and user interface are all
      presented in detail. The paper also explores the expected impact and utility of
      the new Library, as well as some possible future directions for further
      development. CONCLUSION: The Skin Conditions Specialist Library is not just
      another new Web site that dermatologists might want to add to their Internet
      favourites then forget about it. It is intended to be a practical, "one-stop
      shop" dermatology information service for everyday practical use, offering high
      quality, up-to-date resources, and adopting robust evidence-based and knowledge
      management approaches.

PMID- 15854225
TI  - The use of time-resolved fluorescence imaging in the study of protein kinase C
      localisation in cells.
AB  - BACKGROUND: Two-photon-excitation fluorescence lifetime imaging (2P-FLIM) was
      used to investigate the association of protein kinase C alpha (PKCalpha) with
      caveolin in CHO cells. PKCalpha is found widely in the cytoplasm and nucleus in
      most cells. Upon activation, as a result of increased intracellular Ca2+ and
      production of DAG, through G-protein coupled-phospholipase C signalling, PKC
      translocates to a variety of regions in the cell where it phosphorylates and
      interacts with many signalling pathways. Due to its wide distribution, discerning
      a particular interaction from others within the cell is extremely difficult.
      RESULTS: Fluorescence energy transfer (FRET), between GFP-PKCalpha and DsRed
      caveolin, was used to investigate the interaction between caveolin and PKC, an
      aspect of signalling that is poorly understood. Using 2P-FLIM measurements, the
      lifetime of GFP was found to decrease (quench) in certain regions of the cell
      from approximately 2.2 ns to approximately 1.5 ns when the GFP and DsRed were
      sufficiently close for FRET to occur. This only occurred when intracellular Ca2+
      increased or in the presence of phorbol ester, and was an indication of PKC and
      caveolin co-localisation under these conditions. In the case of phorbol ester
      stimulated PKC translocation, as commonly used to model PKC activation, three PKC
      areas could be delineated. These included PKCalpha that was not associated with
      caveolin in the nucleus and cytoplasm, PKCalpha associated with caveolin in the
      cytoplasm/perinuclear regions and probably in endosomes, and PKC in the
      peripheral regions of the cell, possibly indirectly interacting with caveolin.
      CONCLUSION: Based on the extent of lifetime quenching observed, the results are
      consistent with a direct interaction between PKCalpha and caveolin in the
      endosomes, and possibly an indirect interaction in the peripheral regions of the
      cell. The results show that 2P-FLIM-FRET imaging offers an approach that can
      provide information not only confirming the occurrence of specific protein
      protein interactions but where they occur within the cell.

PMID- 15854226
TI  - The role of mutation in the new cancer paradigm.
AB  - The almost universal belief that cancer is caused by mutation may gradually be
      giving way to the belief that cancer begins as a cellular adaptation that
      involves the local epigenetic silencing of various genes. In my own
      interpretation of the new epigenetic paradigm, the genes epigenetically
      suppressed are genes that normally serve in post-embryonic life to suppress and
      keep suppressed those other genes upon which embryonic development depends. Those
      other genes, if not silenced or suppressed in the post-embryonic animal, become,
      I suggest, the oncogenes that are the basis of neoplasia.Mutations that occur in
      silenced genes supposedly go unrepaired and are, therefore, postulated to
      accumulate, but such mutations probably play little or no causative role in
      neoplasia because they occur in already epigenetically silenced genes. These
      mutations probably often serve to make the silencing, and therefore the cancer,
      epigenetically irreversible.

PMID- 15854227
TI  - The Familial Intracranial Aneurysm (FIA) study protocol.
AB  - BACKGROUND: Subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms
      (IAs) occurs in about 20,000 people per year in the U.S. annually and nearly half
      of the affected persons are dead within the first 30 days. Survivors of ruptured
      IAs are often left with substantial disability. Thus, primary prevention of
      aneurysm formation and rupture is of paramount importance. Prior studies indicate
      that genetic factors are important in the formation and rupture of IAs. The long
      term goal of the Familial Intracranial Aneurysm (FIA) Study is to identify genes
      that underlie the development and rupture of intracranial aneurysms (IA).
      METHODS/DESIGN: The FIA Study includes 26 clinical centers which have extensive
      experience in the clinical management and imaging of intracerebral aneurysms. 475
      families with affected sib pairs or with multiple affected relatives will be
      enrolled through retrospective and prospective screening of potential subjects
      with an IA. After giving informed consent, the proband or their spokesperson
      invites other family members to participate. Each participant is interviewed
      using a standardized questionnaire which covers medical history, social history
      and demographic information. In addition blood is drawn from each participant for
      DNA isolation and immortalization of lymphocytes. High- risk family members
      without a previously diagnosed IA undergo magnetic resonance angiography (MRA) to
      identify asymptomatic unruptured aneurysms. A 10 cM genome screen will be
      performed to identify FIA susceptibility loci. Due to the significant mortality
      of affected individuals, novel approaches are employed to reconstruct the
      genotype of critical deceased individuals. These include the intensive
      recruitment of the spouse and children of deceased, affected individuals.
      DISCUSSION: A successful, adequately-powered genetic linkage study of IA is
      challenging given the very high, early mortality of ruptured IA. Design features
      in the FIA Study that address this challenge include recruitment at a large
      number of highly active clinical centers, comprehensive screening and recruitment
      techniques, non-invasive vascular imaging of high-risk subjects, genome
      reconstruction of dead affected individuals using marker data from closely
      related family members, and inclusion of environmental covariates in the
      statistical analysis.

PMID- 15854228
TI  - The importance of APC.
AB  - Readers in immunology are familiar with the importance of antigen presenting
      cells in mounting immune responses. For the purpose of this particular editorial
      article, however, the abbreviation APC will stand for article processing charges.
      The publisher will introduce APCs for this Journal in May, 2005. Here we explain
      why article-processing charges are important to maintain our Open Access journal.

PMID- 15854230
TI  - Relative transcript quantification by quantitative PCR: roughly right or
      precisely wrong?
AB  - BACKGROUND: When estimating relative transcript abundances by quantitative real
      time PCR (Q-PCR) we found that the results can vary dramatically depending on the
      method chosen for data analysis. RESULTS: Analyses of Q-PCR results from a salmon
      louse starvation experiment show that, even with apparently good raw data,
      different analytical approaches 12 may lead to opposing biological conclusions.
      CONCLUSION: The results emphasise the importance of being cautious when analysing
      Q-PCR data and indicate that uncritical routine application of an analytical
      method will eventually result in incorrect conclusions. We do not know the extent
      of, or have a universal solution to this problem. However, we strongly recommend
      caution when analysing Q-PCR results e.g. by using two or more analytical
      approaches to validate conclusions. In our view a common effort should be made to
      standardise methods for analysis and validation of Q-PCR results.

PMID- 15854229
TI  - Human T-cell leukemia virus type I (HTLV-I) infection and the onset of adult T
      cell leukemia (ATL).
AB  - The clinical entity of adult T-cell leukemia (ATL) was established around 1977,
      and human T-cell leukemia virus type 1 (HTLV-I) was subsequently identified in
      1980. In the 25 years since the discovery of HTLV-I, HTLV-I infection and its
      associated diseases have been extensively studied, and many of their aspects have
      been clarified. However, the detailed mechanism of leukemogenesis remains
      unsolved yet, and the prognosis of ATL patients still poor because of its
      resistance to chemotherapy and immunodeficiency. In this review, I highlight the
      recent progress and remaining enigmas in HTLV-I infection and its associated
      diseases, especially ATL.

PMID- 15854231
TI  - Time course study of oxidative and nitrosative stress and antioxidant enzymes in
      K2Cr2O7-induced nephrotoxicity.
AB  - BACKGROUND: Potassium dichromate (K2Cr2O7)-induced nephrotoxicity is associated
      with oxidative and nitrosative stress. In this study we investigated the relation
      between the time course of the oxidative and nitrosative stress with kidney
      damage and alterations in the following antioxidant enzymes: Cu, Zn superoxide
      dismutase (Cu, Zn-SOD), Mn-SOD, glutathione peroxidase (GPx), glutathione
      reductase (GR), and catalase (CAT). METHODS: Nephrotoxicity was induced in rats
      by a single injection of K2Cr2O7. Groups of animals were sacrificed on days
      1,2,3,4,6,8,10, and 12. Nephrotoxicity was evaluated by histological studies and
      by measuring creatinine clearance, serum creatinine, blood urea nitrogen (BUN),
      and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and total protein.
      Oxidative and nitrosative stress were measured by immunohistochemical
      localization of protein carbonyls and 3-nitrotyrosine, respectively. Cu, Zn-SOD,
      Mn-SOD, and CAT were studied by immunohistochemical localization. The activity of
      total SOD, CAT, GPx, and GR was also measured as well as serum and kidney content
      of chromium and urinary excretion of NO2 -/NO3-. Data were compared by two-way
      analysis of variance followed by a post hoc test. RESULTS: Serum and kidney
      chromium content increased reaching the highest value on day 1. Nephrotoxicity
      was made evident by the decrease in creatinine clearance (days 1-4) and by the
      increase in serum creatinine (days 1-4), BUN (days 1-6), urinary excretion of NAG
      (days 1-4), and total protein (day 1-6) and by the structural damage to the
      proximal tubules (days 1-6). Oxidative and nitrosative stress were clearly
      evident on days 1-8. Urinary excretion of NO2-/NO3- decreased on days 2-6. Mn-SOD
      and Cu, Zn-SOD, estimated by immunohistochemistry, and total SOD activity
      remained unchanged. Activity of GPx decreased on days 3-12 and those of GR and
      CAT on days 2-10. Similar findings were observed by immunohistochemistry of CAT.
      CONCLUSION: These data show the association between oxidative and nitrosative
      stress with functional and structural renal damage induced by K2Cr2O7. Renal
      antioxidant enzymes were regulated differentially and were not closely associated
      with oxidative or nitrosative stress or with kidney damage. In addition, the
      decrease in the urinary excretion of NO2-/NO3- was associated with the renal
      nitrosative stress suggesting that nitric oxide was derived to the formation of
      reactive nitrogen species involved in protein nitration.

PMID- 15854232
TI  - Gene expression levels assessed by oligonucleotide microarray analysis and
      quantitative real-time RT-PCR -- how well do they correlate?
AB  - BACKGROUND: The use of microarray technology to assess gene expression levels is
      now widespread in biology. The validation of microarray results using independent
      mRNA quantitation techniques remains a desirable element of any microarray
      experiment. To facilitate the comparison of microarray expression data between
      laboratories it is essential that validation methodologies be critically
      examined. We have assessed the correlation between expression scores obtained for
      48 human genes using oligonucleotide microarrays and the expression levels for
      the same genes measured by quantitative real-time RT-PCR (qRT-PCR). RESULTS:
      Correlations with qRT-PCR data were obtained using microarray data that were
      processed using robust multi-array analysis (RMA) and the MAS 5.0 algorithm. Our
      results indicate that when identical transcripts are targeted by the two methods,
      correlations between qRT-PCR and microarray data are generally strong (r = 0.89).
      However, we observed poor correlations between qRT-PCR and RMA or MAS 5.0
      normalized microarray data for 13% or 16% of genes, respectively. CONCLUSION:
      These results highlight the complementarity of oligonucleotide microarray and qRT
      PCR technologies for validation of gene expression measurements, while
      emphasizing the continuing requirement for caution in interpreting gene
      expression data.

PMID- 15854233
TI  - Practical PCR genotyping protocols for Plasmodium vivax using Pvcs and Pvmsp1.
AB  - BACKGROUND: Plasmodium vivax is the second most prevalent malaria parasite
      affecting more than 75 million people each year, mostly in South America and
      Asia. In addition to major morbidity this parasite is associated with relapses
      and a reduction in birthweight. The emergence and spread of drug resistance in
      Plasmodium falciparum is a major factor in the resurgence of this parasite. P.
      vivax resistance to drugs has more recently emerged and monitoring the situation
      would be helped, as for P. falciparum, by molecular methods that can be used to
      characterize parasites in field studies and drug efficacy trials. METHODS:
      Practical PCR genotyping protocols based on polymorphic loci present in two P.
      vivax genetic markers, Pvcs and Pvmsp1, were developed. The methodology was
      evaluated using 100 P. vivax isolates collected in Thailand. RESULTS AND
      DISCUSSION: Analysis revealed that P. vivax populations in Thailand are highly
      diverse genetically, with mixed genotype infections found in 26 % of the samples
      (average multiplicity of infection = 1.29). A large number of distinguishable
      alleles were found for the two markers, 23 for Pvcs and 36 for Pvmsp1. These were
      generally randomly distributed amongst the isolates. A total of 68 distinct
      genotypes could be enumerated in the 74 isolates with a multiplicity of infection
      of 1. CONCLUSION: These results indicate that the genotyping protocols presented
      can be useful in the assessment of in vivo drug efficacy clinical trials
      conducted in endemic areas and for epidemiological studies of P. vivax
      infections.

PMID- 15854234
TI  - Role of medical therapy in the management of acromegaly.
AB  - Medical therapy plays an important role in the management of patients with
      acromegaly and is commonly used adjunctively after surgical resection of the
      pituitary tumor. Generally, surgery alone provides a 50 to 70% rate of cure;
      however, the outcome depends on the experience and ability of the surgeon and the
      characteristics of the tumor. The role of postsurgical medical therapy is to
      achieve long-term biochemical control of the growth hormone (GH)/insulin-like
      growth factor I (IGF-I) axis. In some patients, medical therapies may be
      implemented sooner as primary or preoperative therapy. Somatostatin analogs have
      been the mainstay of medical therapy for acromegaly. The somatostatin analog
      octreotide produces normalization of IGF-I in approximately 50% of patients but
      is associated with gastrointestinal adverse effects, including the development of
      gallstones. Octreotide requires thrice-daily subcutaneous administration. Long
      acting formulations of somatostatin analogs (octreotide LAR, lanreotide) are at
      least as effective and as well tolerated as short-acting octreotide.
      Unfortunately, some patients are suboptimally responsive to or become intolerant
      of these agents. Pegvisomant belongs to a new class of agents known as GH
      receptor antagonists. This novel agent competitively binds to the GH receptor,
      blocking IGF-I production. Pegvisomant is highly effective in achieving normal
      IGF-I concentrations and in reducing signs and symptoms of acromegaly, even in
      patients resistant to previous treatments. Pegvisomant has been proved safe and
      well tolerated and has no effect on gallbladder motility. GH levels remain
      elevated. Transient elevations in liver enzyme levels require monitoring but
      rarely necessitate termination of therapy. Normalizing IGF-I concentrations with
      pegvisomant also may have a beneficial effect on carbohydrate metabolism and
      cardiovascular risk.

PMID- 15854235
TI  - Analysis of cost related to clinical and angiographic outcomes of aneurysm
      patients enrolled in the international subarachnoid aneurysm trial in a North
      American setting.
AB  - OBJECTIVE: The goal of this study was to compare, in a North American setting,
      the cost-effectiveness of neurosurgical clipping versus endovascular coiling
      treatment of ruptured intracranial aneurysms. A secondary goal was to assess the
      clinical outcomes of patients enrolled into the International Subarachnoid
      Aneurysm Trial (ISAT) from the largest contributing North American center.
      METHODS: Of 230 patients with ruptured intracranial aneurysms, 62 were randomized
      into ISAT at our institution. Of these, 30 were randomized to endovascular
      coiling and 32 to neurosurgical clipping. For these, we evaluated the costs of
      treatment related to all aspects of the inpatient stay, the clinical outcomes at
      2 months and at 1 year using the modified Rankin Scale, and the radiological
      outcomes at 6 months after Guglielmi detachable coiling. RESULTS: There were no
      significant differences in the total cost of treatment between the endovascular
      group and the neurosurgical clipping group. The benefits of apparent decrease in
      length of stay in the endovascular group were offset by higher procedure costs.
      There were no significant differences in clinical outcomes at 2 months and at 1
      year. At 6 months after coiling, 15 (50%) of 30 aneurysms were completely
      obliterated, and 19 (63%) of 30 were angiographically stable. CONCLUSION: The
      high procedure costs of endovascular coiling tended to offset apparent reductions
      in length of stay. Long-term follow-up is indicated both for costs incurred after
      initial treatment and for clinical outcome in patients with incompletely
      obliterated aneurysms.

PMID- 15854236
TI  - Application of nicardipine prolonged-release implants: analysis of 97 consecutive
      patients with acute subarachnoid hemorrhage.
AB  - OBJECTIVE: Since October 1999, nicardipine prolonged-release implants (NPRIs)
      have been used to prevent vasospasm in patients with subarachnoid hemorrhage.
      This study was conducted to examine the incidence of cerebral vasospasm and
      outcome after the application of NPRIs. METHODS: Ninety-seven consecutive
      patients among 125 patients with subarachnoid hemorrhage who were surgically
      treated within 72 hours were analyzed. NPRIs were applied principally to patients
      with thick clots (Fisher Group 3) through a frontotemporal or frontal craniotomy.
      Sixty-nine patients, including five in Fisher Group 2, were treated with NPRIs,
      and 28 were not. NPRIs were placed in the cisterns of thick clots where vasospasm
      was highly probable. RESULTS: Four (6%) of the 69 patients treated with NPRIs and
      3 (11%) of the 28 patients not treated with NPRIs developed delayed ischemic
      neurological deficits (DINDs). Of these patients, clinical deterioration with
      infarction occurred in two patients (3%). Current smoking (P = 0.0088) and
      intraventricular hemorrhage on admission computed tomographic (CT) scans (P =
      0.0077) were correlated with DIND. CT groupings on admission and postoperatively
      were not correlated, nor were World Federation of Neurosurgical Societies grades.
      Hypertension was inversely correlated with DIND (P = 0.0233). Eighty-six patients
      (89%) had an independent status at 3 months. Logistic regression analysis
      demonstrated that age (odds ratio [OR], 6.836; P = 0.034), World Federation of
      Neurosurgical Societies grade (OR, 23.317; P = 0.001), intraventricular
      hemorrhage on admission CT scans (OR, 6.332; P = 0.024), and surgical
      complications (OR, 32.861; P = 0.003) were independent risk factors influencing
      an unfavorable outcome. CT grouping on admission and DIND were not. CONCLUSION:
      Our findings suggest that the incidence of DIND may decrease and, therefore, an
      unfavorable outcome may improve if NPRIs are applied for patients with thick
      clots (Fisher Group 3) during surgery.

PMID- 15854237
TI  - Preoperative cerebral aneurysm assessment by three-dimensional magnetic resonance
      angiography: feasibility of surgery without conventional catheter angiography.
AB  - OBJECTIVE: In this study, we aimed to assess whether surgery could be performed
      in patients with cerebral aneurysms by using three-dimensional (3-D) magnetic
      resonance (MR) angiography alone, without conventional catheter angiography.
      METHODS: A total of 108 patients who had undergone MR angiography and aneurysm
      surgery between January 1998 and January 2004 were enrolled in this study. The
      study subjects included 49 patients without subarachnoid hemorrhage (SAH) and 59
      patients with SAH. RESULTS: In our preliminary study, 13 patients without SAH
      were diagnosed using 3-D MR angiography compared with catheter angiography and 3
      D computed tomographic angiography before surgery. The 3-D MR angiography
      demonstrated all 18 unruptured aneurysms that were detected by catheter
      angiography. Thirty-six patients without SAH and 59 patients with SAH were
      examined using 3-D MR angiography. In 33 patients (91.6%) without SAH and 56
      patients (94.9%) with SAH, we were able to reach a diagnosis on the basis of 3-D
      MR angiography alone. A majority of aneurysms were regular-sized and located in
      the anterior part of the circle of Willis. A total of 89 patients (93.7%) who
      underwent surgery with the aid of 3-D MR angiography alone were treated
      successfully and had no complications related to the lack of information that
      might have been gathered by catheter angiography. The 3-D MR angiography provided
      the authors with the aneurysm locations as well as with surgically important
      information regarding the configuration of the aneurysmal sac and neck and its
      relationship with the surrounding vessels. In the remaining 6 patients, 3-D MR
      angiography was followed by catheter angiography to acquire additional diagnostic
      confirmation. CONCLUSION: The results of this study support the notion that 3-D
      MR angiography can replace conventional catheter angiography for preoperative
      assessment in the majority of regular-sized anterior circulation aneurysms.

PMID- 15854238
TI  - Carotid tissue levels of argatroban after direct local delivery during carotid
      endarterectomy to prevent perioperative cerebral embolism.
AB  - OBJECTIVE: Argatroban is a synthetic direct thrombin inhibitor. We applied
      argatroban locally during carotid endarterectomy to prevent local mural thrombus
      formation. Although local delivery of argatroban is expected to be effective for
      inhibition of mural clot formation, there is no report of the evaluation of its
      clinical effectiveness or local drug concentration in humans. METHODS: Five mg of
      argatroban (0.5 mg/ml) was applied twice intraoperatively just after arteriotomy
      for measurement of intraplaque level of argatroban and during closure of the
      arteriotomy for preventing thrombus formation. After exposure of the carotid
      plaque to argatroban for a specified duration (0, 3, 5, or 10 min), argatroban
      was sufficiently washed with saline and the carotid plaque was removed for
      measurement of tissue concentration of argatroban. Intraplaque level of
      argatroban was determined by high-performance liquid chromatography. A second
      application was performed during closure of the arteriotomy. Argatroban was
      applied for 10 minutes, followed by washing with saline. Postoperative embolic
      cerebrovascular complications and carotid restenosis also were investigated to
      verify the efficacy of direct local application of argatroban. RESULTS: Tissue
      levels of argatroban in the carotid plaque after 3, 5, and 10 minutes of direct
      application were 24.0 +/- 13.7, 31.6 +/- 20.0, and 44.0 +/- 15.1 mug/g,
      respectively. The concentrations at all time points were significantly elevated
      compared with the control, and a significant difference in concentration was
      observed between 3 minutes and 10 minutes. In the present study, concentration at
      3 minutes was much higher than the effective tissue levels of argatroban reported
      in experimental studies. No patient developed postoperative cerebrovascular
      complications. CONCLUSION: The results suggest that direct local application of
      argatroban during carotid endarterectomy for at least 3 minutes may deliver high
      local tissue levels. Argatroban may be effective for prevention of perioperative
      embolic cerebral complications during carotid endarterectomy.

PMID- 15854239
TI  - Comparison of magnetic resonance spectroscopy and perfusion-weighted imaging in
      presurgical grading of oligodendroglial tumors.
AB  - OBJECTIVE: Oligodendroglial tumors form an uncommon, but distinct, subgroup of
      gliomas with longer survival, better treatment response, and characteristic
      genetic alterations. Noninvasive grading of oligodendroglial tumors using
      functional and metabolic magnetic resonance imaging may be helpful in guiding the
      treatment approach and predicting malignant transformation of these tumors. We
      used perfusion-weighted magnetic resonance imaging and proton magnetic resonance
      spectroscopic imaging (MRSI) to predict the oligodendroglioma grade. METHODS:
      Twenty-four patients with pathologically confirmed oligodendrogliomas underwent
      dynamic contrast-enhanced perfusion-weighted magnetic resonance imaging and/or
      proton MRSI before surgery. We assessed the ability of tumor contrast
      enhancement, normalized cerebral blood volume, normalized choline, and the
      presence of either lactate or lipid metabolites to correctly predict the World
      Health Organization tumor grade. The accuracy of tumor grading using each method
      was also compared. RESULTS: Tumor contrast enhancement (P = 0.069) and normalized
      cerebral blood volume (P = 0.181) were not significantly different between low
      and high-grade oligodendrogliomas. The MRSI measurement of normalized choline was
      significantly higher in high-grade (2.82 +/- 0.64) than in low-grade (1.62 +/-
      0.46) oligodendrogliomas (P < 0.001), and the presence of lactate or lipid
      metabolites also correctly predicted high-grade tumors (P = 0.014). The maximum
      accuracy of contrast enhancement, normalized cerebral blood volume, normalized
      choline, and lactate or lipid metabolites in grading oligodendroglioma was 71,
      83, 90, and 85%, respectively. CONCLUSION: MRSI measurements are more accurate
      than perfusion-weighted magnetic resonance imaging or conventional contrast
      enhancement in differentiating oligodendroglial tumor grade. In these inherently
      vascular tumors, metabolic measurements of mitosis and necrosis may be better
      than measures of neovascularity in presurgical grading.

PMID- 15854240
TI  - Vestibular schwannomas: clinical results and quality of life after microsurgery
      or gamma knife radiosurgery.
AB  - OBJECTIVE: The aim of the present study was to evaluate the overall treatment
      efficacy (tumor control, facial nerve function, complications) and quality of
      life for patients treated primarily for unilateral vestibular schwannomas of 30
      mm or less, either by microsurgery or by gamma knife (GK) radiosurgery. The
      results for the two treatment groups are compared with each other, with main
      emphasis on the long-term quality of life. METHODS: This is a retrospective study
      of 189 consecutive patients, 86 treated by microsurgery and 103 by gamma knife.
      The mean observation time was 5.9 years. All patients had a magnetic resonance
      imaging scan and clinical evaluation performed toward the end of the study. To
      evaluate the quality of life, we used two standardized questionnaires, the
      Glasgow Benefit Inventory and Short-Form 36. The questionnaires were sent to the
      168 living patients. The reply rate was 83.3%. RESULTS: A total of 79.8% of the
      patients in the microsurgery group and 94.8% of the GK patients had a good facial
      nerve function (House-Brackmann Grade 1-2). Hearing was usually lost after
      microsurgery, whereas the GK patients had preserved hearing, which often became
      reduced over the years after the treatment. The treatment efficacy, defined as no
      need for additional treatment, was similar for the two treatment modalities.
      Quality of life was reduced compared with normative data, being most reduced in
      the microsurgery group. Some of the quality of life questions showed an
      association with facial nerve function and sex. CONCLUSION: Posttreatment facial
      nerve function, hearing, complication rates, and quality of life were all
      significantly in favor of GK radiosurgery.

PMID- 15854241
TI  - Outcome variation among "radioresistant" brain metastases treated with
      stereotactic radiosurgery.
AB  - OBJECTIVE: To determine the influence of histopathological diagnosis on the
      outcome of "radioresistant" brain metastases treated with stereotactic
      radiosurgery (SRS). METHODS: Patients (n = 189) with "radioresistant" brain
      metastases (n = 264) were consecutively treated with SRS between August 1991 and
      July 2002. The primary site of brain metastases was melanoma (n = 103), renal
      cell carcinoma (n = 77), and sarcoma (n = 9). The median age of the patients was
      52 years, and the median Karnofsky Performance Scale score was 80. Initial brain
      metastasis presentation was single in 112 patients (59%). The median SRS dose was
      18 Gy (range, 10-24 Gy). The median tumor volume was 1.6 cm3 (range, 0.06-27.5
      cm3). The median follow-up of all patients was 7.4 months (range, 0.16-52 mo).
      RESULTS: The actuarial freedom from progression after 1 year was 64% for renal
      cell carcinoma patients, 47% for melanoma patients, and 0% for sarcoma patients
      (P < 0.001). The median survival time for all patients from time of SRS was 7.5
      months. The rate of 1-year survival was 40% for renal cell carcinoma patients,
      25% for melanoma patients, and 22% for sarcoma patients (P = 0.0354). The
      incidence of neurological death was lower among patients diagnosed with renal
      cell carcinoma (31%) than among patients with melanoma (66%) or sarcoma (60%) (P
      = 0.001). CONCLUSION: Survival after SRS is significantly worse for patients with
      melanoma and sarcoma brain metastases compared with patients with renal cell
      carcinoma. Our data show that progressive brain metastases seem to cause most of
      the cancer-related deaths among patients with SRS-treated melanoma and sarcoma
      brain metastases. Future investigations using chemotherapy or novel agents to
      enhance the effectiveness of SRS to melanoma and sarcoma brain metastases seem
      warranted.

PMID- 15854242
TI  - Growth pattern changes of meningiomas: long-term analysis.
AB  - OBJECTIVE: Although tumors are generally expected to grow exponentially, it is
      not known whether meningiomas retain a constant growth rate or not because of the
      lack of long-term follow-up. We analyzed the long-term growth pattern of
      meningiomas. METHODS: Twenty patients with a total of 31 meningiomas were
      radiologically followed for 4.1 to 18.3 years (median, 10.1 yr). Seven patients
      (including two neurofibromatosis cases) had incidental tumors. Another 13
      patients with symptomatic tumors were followed after surgery. Their volumes were
      measured, and their time-volume curves were plotted. RESULTS: The growth curves
      of four atypical meningiomas fitted better to an exponential curve (R > 0.95).
      Two calcified tumors did not grow. Although the other benign tumors grew
      exponentially or linearly, their tumor volume doubling times in the initial phase
      were shorter than those in the later phase in most cases. Meningiomas without
      calcification tended to grow exponentially, whereas those with calcification were
      likely to reveal a linear growth pattern (P = 0.002, chi2 test). This was
      supported by the observation that in two patients, the tumor growth pattern
      changed from exponential to linear and from linear to no growth with progression
      of calcification. CONCLUSION: Three growth patterns of meningiomas were
      demonstrated. Atypical meningiomas grew exponentially. Conversely, benign
      meningiomas revealed exponential, linear, or no growth. The growth pattern of the
      latter may change with the appearance of calcification.

PMID- 15854243
TI  - Thirty-seven cases of intracranial meningiomas in the ninth decade of life: our
      experience and review of the literature.
AB  - OBJECTIVE: We report a series of 37 elderly patients who were surgically treated
      for intracranial meningioma in the ninth decade of life at our neurosurgical
      division between 1985 and 2002. METHODS: Our study included 37 patients ranging
      in age from 80 to 86 years (29 women, 8 men). The preoperative neurological
      status was evaluated according to Karnofsky Performance Scale (KPS) status. The
      patients' general health condition was evaluated according to the American
      Society of Anesthesiology (ASA) classification. RESULTS: Five patients (13.5%)
      experienced perioperative mortality. The risk of postoperative mortality was
      higher in patients graded as ASA Class III who had low preoperative KPS ratings
      (< 70), whereas it was lower in patients graded as ASA Classes I and II (P >
      0.001). The postoperative mortality rate was significantly higher in patients
      graded as having a KPS score of less than 70 (P > 0.01). The risk of
      postoperative morbidity seems higher with larger maximum tumor diameters (P <
      0.05). Surgical excision and the presence of a severe peritumoral edema seem to
      be associated with a higher risk of postoperative morbidity (P < 0.05).
      CONCLUSION: Surgical removal of a meningioma in the elderly is a safe procedure
      if the preoperative ASA classification is I or II and if the KPS rating is at
      least 70. Age seems not to be an insuperable obstacle when adequate management of
      all risk factors has been obtained.

PMID- 15854244
TI  - Cerebral perfusion pressure between 50 and 60 mm Hg may be beneficial in head
      injured patients: a computerized secondary insult monitoring study.
AB  - OBJECTIVE: To describe the occurrence of secondary insults using a computerized
      monitoring data collecting system and to investigate their relationship to
      outcome when the neurointensive care was dedicated to avoiding secondary insults.
      METHODS: Patients 16 to 79 years old admitted to the neurointensive care unit
      between August 1998 and December 2002 with traumatic brain injury and 54 hours or
      more of valid monitoring within the first 120 hours after trauma (one value/min)
      were included. Monitoring of intracranial pressure (ICP), cerebral perfusion
      pressure (CPP), systolic blood pressure (BPs), and mean blood pressure (BPm) was
      required, and insult levels were defined (ICP >25/>35, BPs <100/<90/>160/>180,
      BPm <80/<70/>110/>120, and CPP <60/<50/>70/>80 mm Hg). Insults were quantified as
      proportion of valid monitoring time at the insult level. Logistic regression
      analyses were performed with admission and secondary insult variables as
      explanatory variables and favorable outcome as dependent variable. RESULTS:
      Eighty-one patients, 63 men and 18 women, with a mean age of 43.0 years,
      fulfilled the inclusion criteria. Seventy-two patients (89%) had Glasgow Coma
      Scale scores of 8 or less. Thirty-one patients (38%) had diffuse injury, and 50
      (62%) had mass lesions. Mean Injury Severity Score was 26.6. After 6 months, 54%
      of the patients had achieved a favorable outcome. Most patients spent 5% or less
      of the monitoring time at the insult level except for CPP greater than 70 mm Hg.
      Low age, high Glasgow Coma Scale motor score, low Injury Severity Score, and CPP
      less than 60 mm Hg insults were significant predictors of favorable outcome in
      the final multiple logistic regression model. CONCLUSION: Overall, the secondary
      insults were rare, except for high CPP. The results suggest that patients with
      traumatic brain injury might benefit from a CPP slightly less than 60 mm Hg.

PMID- 15854245
TI  - Long-term follow-up of intramedullary spinal cord tumors: a series of 202 cases.
AB  - OBJECTIVE: To review a series of patients who underwent surgical removal of
      intramedullary spinal cord tumors, focusing on the long-term functional outcome,
      recurrence rates for the various tumors, and technical problems continually
      debated in neurosurgical practice. METHODS: From December 1972 to June 2003, 202
      patients underwent removal of intramedullary tumors. Lesions were located in the
      cervical spinal cord in 61 patients (30%), at a dorsal site in 60 (29%), at a
      cervicodorsal site in 51 (25%), and in the medullary cone in 30 (15%). The most
      frequent histological tumor types were astrocytomas (86 patients, 42%) and
      ependymomas (68 patients, 34%). RESULTS: Of the 68 ependymomas, 55 (81%) were
      completely removed and 13 (19%) incompletely removed. In 66% of the patients (42
      patients), the presenting signs and symptoms remained unchanged at long-term
      follow-up; in 25% (16 patients), they improved; and in 9% (6 patients), the
      clinical status worsened. Of the 27 Grade I astrocytomas, 22 (81%) were
      completely removed and 5 (19%) incompletely removed. Functional assessment of the
      23 patients available at "late" follow-up showed that 26% (6 of 23 patients) had
      improved, 9% (2 of 23 patients) had worsened, and 66% (15 of 23 patients)
      remained unchanged from preoperative status. Conversely, of the 41 Grade II
      astrocytomas, only 5 (12%) were completely removed, and 10% had improved. None of
      the 18 Grade III to IV astrocytomas could be completely removed. In 61% (11 of 18
      patients), the postoperative functional status worsened. CONCLUSION: Determinant
      predictors of a good outcome after surgery for intramedullary spinal cord tumors
      are histological type of lesion, complete removal of the lesion, and a
      satisfactory neurological status before surgery.

PMID- 15854246
TI  - Changes in transcranial motor evoked potentials during intramedullary spinal cord
      tumor resection correlate with postoperative motor function.
AB  - OBJECTIVE: Intraoperative monitoring of transcranial motor evoked potentials
      (TcMEPs) has been investigated recently as a means of preventing motor deficits
      associated with resection of intramedullary spinal cord tumors (IMSCTs). In this
      study, we hypothesized that changes in the intraoperative MEPs during tumor
      resection correlate with postoperative motor function deficits. METHODS: A
      retrospective record review was conducted for 28 patients who underwent resection
      of an IMSCT using myogenic or muscle-recorded TcMEPs during a 44-month period.
      Intraoperative MEP recordings and results from preoperative, immediate
      postoperative, and subsequent follow-up neurological examinations were analyzed.
      RESULTS: Of the 28 patients who underwent resection of an IMSCT using TcMEPs, MEP
      changes occurred in 13 patients (46%). Impaired motor conduction was detected by
      changes in pattern and duration of the MEP waveform morphology (polyphasic to
      biphasic in 9 patients and polyphasic to biphasic to loss of MEP response in 5
      patients, 1 patient demonstrated both changes) and by an increase in voltage
      threshold (median, 175 V; range, 100-225 V; n = 22 extremities). Alterations in
      morphology and reduction in duration of the MEP response persisted despite
      significant increases in stimulation voltage. In 12 patients, reductions in the
      complexity and/or loss of the TcMEP waveform correlated with motor grade loss in
      the immediate postoperative period (P < 0.0001), at discharge (P < 0.001), and at
      follow-up (P < 0.001). The decrease in the duration of the response correlated
      with motor grade loss immediately after surgery (P < 0.001), at discharge (P <
      0.0001), and at follow-up (P < 0.005). CONCLUSION: These results support the
      application of distal muscle-recorded TcMEPs to predict the occurrence and
      severity of postoperative motor deficits during resection of IMSCTs. Attention to
      such quantitative intraoperative monitoring data may help to minimize
      postoperative motor deficits by avoiding or correcting excessive spinal cord
      manipulation and modifying surgical technique during tumor resection.

PMID- 15854247
TI  - Lost productive work time after mild to moderate traumatic brain injury with and
      without hospitalization.
AB  - OBJECTIVE: Lost productivity after mild traumatic brain injury (TBI) is a large
      component of the economic costs of brain trauma in the United States. This is the
      first prospective study of employment after mild TBI to include patients not
      admitted to a hospital. METHODS: Concurrent inception cohorts of 210 working-age
      adults with mild to moderate TBI and 122 patients who sustained general trauma
      not involving the brain were recruited at a trauma center and followed up to 6
      months later. Outcomes were time from injury until first day worked and problems
      reported after resuming work. RESULTS: Most patients who worked after their
      injury remained employed 6 months later in a similar capacity as before the
      injury. No consistent differences were demonstrated between employment outcomes
      of patients with mild TBI and those with general trauma. The majority of
      nonhospitalized patients with mild TBI did not work for at least 1 month and did
      not begin working until 1 to 3 months after injury. Most patients with moderate
      TBI remained unemployed at 6 months postinjury. Patients with lower preinjury
      occupational status tended to have longer work absences. CONCLUSION: Lost
      productive work time after nonhospitalized TBI may cause significant economic
      costs because these injuries are frequent. Contrary to the theory that brain
      injury is more disabling to patients in cognitively demanding occupations,
      patients with higher job status tended to begin work earlier. A technique is
      needed to screen patients with mild TBI for risk of employment problems.
      Rehabilitation after moderate TBI may help to minimize lost productivity.

PMID- 15854248
TI  - Surgical management of remote, isolated type II odontoid fractures with
      atlantoaxial dislocation causing cervical compressive myelopathy.
AB  - OBJECTIVE: The remote (more than 6 mo after injury) and isolated (not associated
      with any other cervical spinal fractures) Type II fractures of the odontoid (RI
      IIO) are unique in being inherently unstable and prone to malunion or nonunion,
      leading to cervical compressive myelopathy. The present study discusses their
      surgical management. METHODS: Nineteen patients with RI IIO with atlantoaxial
      dislocation (AAD) causing compressive myelopathy were treated. Their preoperative
      disability was graded as Grade I: neurologically intact (presented with
      hyperreflexia and mild spasticity; n = 3); Grade II: independent with minor
      disability (n = 7); Grade III: partially dependent for daily needs (n = 6); and
      Grade IV: totally dependent (n = 3). They were classified as irreducible AAD
      caused by 1) malunited fracture of the odontoid (n = 2), 2) fixed anterolisthesis
      of the anterior arch of a C1-fractured odontoid complex (n = 3), and 3) fixed
      retrolisthesis of the anterior arch of a C1-fractured odontoid complex (n = 1);
      and reducible AAD caused by 1) mobile AAD (n = 11) and 2) hypermobile AAD (n =
      2). The patients with irreducible AAD underwent a transoral decompression and
      posterior fusion; those with a malunited fracture underwent surgery immediately,
      whereas those with fixed anterolisthesis or retrolisthesis were initially placed
      in cervical traction. The patients with reducible AAD underwent a direct
      posterior fusion. In the patient with "hypermobile" AAD, a proper alignment of
      the fractured segment of the odontoid relative to the body of the axis in a
      neutral position of the neck was ensured before the posterior fusion was
      performed. RESULTS: At follow-up (mean, 15.37 +/- 9.67 mo), three patients in
      Grade I maintained their neurological status. Of the seven patients in Grade II
      and six in Grade III, five had improved to Grade I, and eight were in Grade II.
      The three patients in Grade IV improved to Grade I, II, and III, respectively.
      CONCLUSION: The patients with RI IIO may be divided into five groups on the basis
      of their differing management protocols. There is a considerable risk of delayed
      myelopathy unless surgical reduction and stabilization are performed. Posterior
      stabilization is the preferred option in dealing with these fractures. Despite
      the presence of severe neurological deficits and the prolonged duration of
      symptoms, a significant neurological improvement usually occurs after surgery.

PMID- 15854249
TI  - Surgical management of 33 ilioinguinal and iliohypogastric neuralgias at
      Louisiana State University Health Sciences Center.
AB  - OBJECTIVE: This is a retrospective review of 33 charts of patients with
      ilioinguinal and iliohypogastric neuralgias who underwent a neurectomy at
      Louisiana State University Health Sciences Center between 1967 and 2000.
      Operations associated with neuralgias and postoperative pain outcomes were
      analyzed. METHODS: There were 23 ilioinguinal and 10 combined ilioinguinal
      iliohypogastric neuralgias, and the side of the lesion and sex of the patient
      were found to be evenly distributed in this group. Nerve blocks must have
      resulted in a complete or substantial decrease in pain before a neurectomy was
      recommended. Twenty-nine (88%) of 33 neuralgia patients had injuries from
      iatrogenic causes, and 4 (12%) injuries were caused by blunt trauma. In the 23
      isolated ilioinguinal neuralgias, the operation associated with neuralgias in 13
      (57%) of 23 patients was a herniorrhaphy. This was followed by 4 (17%) neuralgias
      after an appendectomy and 3 (13%) after a hysterectomy. Three (13%) patients had
      neuralgias resulting from blunt trauma. Nine (90%) of 10 ilioinguinal
      iliohypogastric lesions were caused by iatrogenic causes, and 1 (10%) neuralgia
      resulted from blunt trauma. A neurectomy was performed in all patients. RESULTS:
      The neurectomy resulted in considerable pain relief in 21 (91%) of 23 patients
      with ilioinguinal lesions and 9 (90%) of 10 patients with ilioinguinal
      iliohypogastric lesions. Postoperative side effects were persistent numbness
      below the resected nerve and loss of the cremasteric reflex. Minor postoperative
      complications consisted of two superficial skin infections. CONCLUSION:
      Ilioinguinal and ilioinguinal-iliohypogastric neuralgias are infrequent
      conditions; however, 33 patients from the Louisiana State University Health
      Sciences Center were accrued and analyzed in this study, and most had significant
      pain relief after neurectomy.

PMID- 15854250
TI  - Reevaluation of surgery for the treatment of brain metastases: review of 208
      patients with single or multiple brain metastases treated at one institution with
      modern neurosurgical techniques.
AB  - OBJECTIVE: Patients with brain metastases were analyzed retrospectively to assess
      the risks and benefits of surgery with modern neurosurgical techniques, including
      image guidance coupled as indicated with corticography. METHODS: We
      retrospectively analyzed charts of patients treated surgically for brain
      metastases. We identified patients with single or multiple brain metastases who
      underwent craniotomies to reverse associated neurological symptoms or establish a
      diagnosis. We assessed patients according to recursive partitioning analysis
      (RPA) prognostic groups as well as functional grades of tumor location (eloquent
      versus noneloquent, Grades I-III). Perioperative complications, neurological
      outcomes after surgery, survival, and prognostic factors were analyzed.
      Statistical analysis of survival was performed with the Kaplan-Meier method. A P
      value of <0.05 was considered statistically significant. RESULTS: Two hundred
      eight patients were treated between March 1995 and December 2002. Patient age
      ranged from 31 to 82 years (median, 59 yr). One lesion was resected in 191
      patients, and of 76 patients with multiple lesions, two or more metastases were
      resected in 17 patients. Tumors were located in eloquent cortex in 27 patients
      and near eloquent cortex in 124 patients. Four patients died within 30 days after
      surgery for a mortality rate of 1.9%. Neurological deterioration was noted in 13
      patients (6%) after surgery for Grade I and II tumors and in 5 patients (19%) of
      27 patients with Grade III tumors. Karnofsky Performance Scale scores were
      improved (68 patients) or unchanged (124 patients) in 192 patients and worse in
      16 patients after surgery. The median survival time (MST) from the date of
      surgery was 8 months for all patients and 9 months for 163 patients who did not
      undergo prior whole-brain radiation therapy. There was no difference in survival
      between patients operated for single metastasis (MST, 8 mo) versus patients with
      two or three metastases (MST, 9 mo; P = 0.9364). By both univariate and
      multivariate analysis, variables significantly affecting outcome included a high
      Karnofsky Performance Scale score and RPA Class I assignment. By univariate
      analysis, significant treatment variables included postoperative radiotherapy and
      postoperative chemotherapy. The MSTs of RPA Class I, II, and III patients were
      16.1 months, 7.2 months, and 1.4 months, respectively (P < 0.001, log-rank test).
      These survival data compare favorably with the stereotactic radiosurgery boost
      arm of the recently published Radiation Therapy Oncology Group 9508 trial.
      CONCLUSION: In most patients with single or multiple brain metastases, surgical
      resection reversed or stabilized neurological symptoms with therapeutic benefit,
      conveying a notable survival advantage without apparent increased risk,
      particularly in RPA Class I patients. In patients with Grade III single
      metastasis or RPA Class II multiple metastasis, surgical judgment should be
      exercised, and stereotactic radiosurgery boost treatment may be preferable. An
      algorithm for treatment of brain metastases is proposed.

PMID- 15854251
TI  - Y-configured dual intracranial stent-assisted coil embolization for the treatment
      of wide-necked basilar tip aneurysms.
AB  - OBJECTIVE: Despite advances in both the surgical and endovascular treatment of
      intracranial aneurysms, wide-necked basilar tip aneurysms (i.e., basilar tip
      aneurysms in which both posterior cerebral arteries emanate from the base of a
      wide-necked aneurysm) represent a subset of aneurysms that continues to pose
      technical challenges in treatment. We sought to demonstrate the safety and short
      term durability of a novel dual stent-assisted coil embolization technique.
      METHODS: Two Neuroform stents (Boston Scientific/Target, Fremont, CA) were
      deployed in the posterior cerebral arteries and the basilar artery, one passing
      through the interstices of the other in a Y-configuration, thereby recreating an
      aneurysm neck and enabling safe coil delivery while preserving the parent
      vessels. RESULTS: Seven patients with unruptured, asymptomatic, wide-necked
      basilar tip aneurysms involving both posterior cerebral arteries and ranging in
      size from 7 to 20 mm underwent treatment with this stent-assisted coiling
      technique. Two stents were successfully deployed in six of the patients and one
      stent was successfully deployed in the seventh. One patient developed a transient
      internuclear ophthalmoplegia, and another experienced transient partial right
      oculomotor nerve palsy. All aneurysms had complete or near-complete embolization
      with the initial procedure. Follow-up angiography performed 6 months (six
      patients) and 1 year (one patient) after treatment demonstrated coil compaction
      and slight recanalization in one patient and recanalization requiring retreatment
      in another. All patients were neurologically intact at least 6 months after the
      initial procedure, as well as subsequent procedures, without clinical signs of
      subarachnoid hemorrhage. CONCLUSION: These initial technical and clinical results
      are highly encouraging, and this technique may significantly improve the
      endovascular treatment of intracranial aneurysms.

PMID- 15854252
TI  - Antimicrobial-impregnated external ventricular catheters: does the very low
      infection rate observed in clinical trials apply to daily clinical practice?
AB  - OBJECTIVE: A recent multicenter, randomized, prospective study using
      antimicrobial-impregnated ventricular catheters (AIVCs) has demonstrated a
      dramatic reduction in the incidence of catheter-related infections. By necessity,
      such trials are subject to notoriously close and careful monitoring; thus, the
      results of multicenter, randomized clinical trials do not automatically apply to
      daily clinical practice. The aim of the present study was to establish whether
      the very low incidence of ventriculitis with AIVCs reported in these trials is
      also observed in routine clinical practice. METHODS: Data on 139 consecutive
      patients admitted to a Neurocritical Intensive Care Unit who underwent placement
      of 154 AIVCs were reviewed. All patients included in the data analysis had an
      AIVC for at least 48 hours, and cultures as well as cell counts were obtained
      from the CSF at various intervals after placement of the AIVC. RESULTS: One
      hundred thirteen catheters in 100 patients met criteria for inclusion in the
      analysis. There were four positive cultures. In three patients, the culture
      result was thought to be a contaminant (because it was not corroborated by
      clinical findings or cell count or because of the characteristics of the
      culture). Only one gram-negative infection was considered to be clinically
      significant (0.88% of catheters, 1.00% of patients) and confirmed on clinical and
      other laboratory grounds. CONCLUSION: The very low infection rate with currently
      available AIVCs observed in rigorously controlled clinical trials translates to
      routine clinical practice.

PMID- 15854253
TI  - Transoral odontoidectomy.
AB  - The transoral approach for odontoidectomy is described in detail, and the
      operating room setup and surgical positioning are demonstrated. We also discuss
      our methods of retractor placement and techniques for optimal surgical exposure.
      The microsurgical technique used for decompression is presented in detail. The
      surgical pearls and pitfalls of transoral odontoidectomy, learned from a 70-case
      experience, are described and illustrated.

PMID- 15854254
TI  - Clinicopathological review: tumefactive demyelination in a 12-year-old girl.

PMID- 15854255
TI  - Coexpression of angiogenic factors in brain arteriovenous malformations.
AB  - OBJECTIVE: Brain arteriovenous malformations (BAVMs) are structurally unstable
      blood vessels that display an angiogenic phenotype, possibly maintained by
      concerted effects of key angiogenic factors. Therefore, we hypothesized that
      there are close correlations among key angiogenic factors in BAVMs and that
      levels of key angiogenic factors are associated with BAVM clinical
      characteristics that are linked with vascular instability. METHODS: We measured
      the expression of angiopoietin-2 (Ang-2), matrix metalloproteinase-9, vascular
      endothelial growth factor (VEGF), and platelet-derived growth factor-AA and -BB
      by use of enzyme-linked immunosorbent assay in 27 BAVM surgical specimens.
      Tissues were also collected from 14 structurally normal brain specimens obtained
      during epilepsy surgery. RESULTS: Ang-2, VEGF, and matrix metalloproteinase-9
      were highly expressed in BAVM samples (11.9 +/- 15.5 ng/mg protein, 137 +/- 102
      pg/mg protein, and 379 +/- 455 pg/mg protein, respectively). Platelet-derived
      growth factor-BB was detectable in 7 of 21 BAVM samples. There were close
      correlations between Ang-2 and VEGF (R2 = 0.79). Higher Ang-2 and VEGF levels
      seemed to be associated with draining vein characteristics linked with BAVM
      hemorrhage but not with feeding artery pressure or BAVM size. In the structurally
      normal brain specimens, levels of Ang-2, VEGF, and matrix metalloproteinase-9
      were low (0.8 +/- 2.3 ng/mg protein, 38 +/- 25 pg/mg protein, and 52 +/- 43 pg/mg
      protein, respectively). CONCLUSION: There were close correlations among
      angiogenic factors in BAVMs. Concerted effects of angiogenic factors may maintain
      the angiogenic phenotype in BAVMs and thereby determine the clinical course of
      BAVMs.

PMID- 15854256
TI  - Pituitary carcinoma: a clinicopathological review.
AB  - Pituitary carcinomas are rare tumors; less than 100 well-documented cases have
      been reported to date. Such tumors are aggressive and associated with a high
      mortality rate. The molecular events leading to the development of pituitary
      carcinomas are largely unknown. Recent studies have only begun to shed light on
      the probable mechanisms of tumor initiation and progression. A review of the
      clinicopathological and molecular genetic characteristics of pituitary carcinomas
      is presented.

PMID- 15854257
TI  - Accelerated embolization healing of aneurysms by polyethylene terephthalate coils
      seeded with autologous fibroblasts.
AB  - OBJECTIVE: The objective of this study was to develop a therapeutic system of
      aneurysm embolization on the basis of organization of fibrous tissue. The healing
      process of aneurysms by means of polyethylene terephthalate (PET) fiber coils
      seeded with autologous fibroblasts was evaluated. METHODS: The aneurysm was
      prepared at the common carotid artery of 42 rabbits by end-to-side anastomosis of
      the jugular vein pouch. PET fiber coils seeded with or without autologous
      fibroblasts were applied to the aneurysm. Assessment of the tissue appearance and
      histological examination were performed 3 and 5 weeks after application to
      evaluate the area embolized by fibrous organization in the aneurysm and the
      neointima formation at the aneurysm orifice. RESULTS: An agitated seeding method
      enabled autologous fibroblasts to attach and proliferate homogeneously on the PET
      fiber coil. In contrast to the PET fiber coil, the PET fiber coil seeded with
      autologous fibroblasts accelerated the organization of fibrous tissue in the
      aneurysm and time to achieve aneurysm embolization. The aneurysm orifice was
      closed with neointima formed. The aneurysm was histologically embolized with
      newly formed fibrous tissue, and the area embolized was significantly larger than
      that of nontreated and the PET fiber coil-treated groups. The orifice was
      completely covered with endothelial cells. CONCLUSION: The PET fiber coil seeded
      with autologous fibroblasts is a promising tool for healing aneurysms using
      embolization therapy by tissue organization.

PMID- 15854258
TI  - Inflammation in the brain after experimental subarachnoid hemorrhage.
AB  - OBJECTIVE: To study the occurrence of an inflammatory response in the brain after
      subarachnoid hemorrhage and its relation to the decrease in acute cerebral blood
      flow, subarachnoid blood proximity, and cell damage. METHODS: Subarachnoid
      hemorrhage was induced in rats via endovascular perforation of the internal
      carotid artery or injection of blood into the prechiasmatic cistern. Cerebral
      blood flow was measured by laser Doppler flowmetry for 60 minutes. After 2 and 7
      days, the brains were analyzed by immunohistochemistry using the following
      antibodies: OX6, ED1, intercellular adhesion molecule 1, tumor necrosis factor
      alpha, interleukin-1beta, interleukin-6, inducible nitric oxide synthase, and
      nestin. Deoxyribonucleic acid fragmentation was assessed using terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labeling. RESULTS: In approximately half of the surviving animals (0-92%,
      depending on the marker and subgroup), signs of inflammation were detected. The
      most common findings were increased immunoreactivity to nestin, ED1, OX6,
      intercellular adhesion molecule 1, and tumor necrosis factor alpha. There was
      great variability in the intensity and the location of the inflammatory reaction
      among the animals, but tissues in proximity to the extravasated blood seemed to
      be especially affected. A significant correlation between the duration of
      cerebral blood flow under 30% of the baseline and the degree of the inflammation
      was observed. There was a strong correspondence between areas showing
      deoxyribonucleic acid fragmentation and inflammation. CONCLUSION: Subarachnoid
      hemorrhage triggered an inflammatory reaction in the brain in a large fraction of
      the surviving animals, which may have contributed to cell death. Acute ischemic
      episodes and direct effect of blood seemed to be significant factors in its
      genesis.

PMID- 15854259
TI  - Disorganization of the facial nucleus after nerve lesioning and regeneration in
      the rat: effects of transplanting candidate reparative cells to the site of
      injury.
AB  - OBJECTIVE: After the facial nerve has been damaged, functional recovery is
      impaired by synkinesis: the abnormal movement of part of the face during
      voluntary movement of another part. This is primarily because of aberrant
      regenerating axons that fail to reach the correct distal targets. We studied the
      effects of transplanting Schwann cells, mixed olfactory ensheathing cells, and S
      type olfactory ensheathing cells on the histological and functional organization
      of the connections between the facial nucleus and distal muscles. METHODS: In a
      control group of adult rats (n = 18), the proximal part of the extracranial
      facial nerve was completely severed and immediately repaired by suture. In an
      experimental group (n = 34), a bolus of cultured cells was applied to the cut
      ends before suture (Schwann cells, n = 10; olfactory ensheathing cells, n = 18; S
      type cells, n = 6). A period of regeneration was permitted, after which the
      animals were assessed functionally by measurement of eye closure in response to a
      puff of air. The site of lesion and the somatotopic organization of the facial
      nucleus were assessed histologically, after application of different retrograde
      fluorescent tracers simultaneously to the buccal and temporal divisions of the
      facial nerve. RESULTS: The rate of recovery of eye closure was increased by the
      use of the cell transplants, but the disorganization of the facial nucleus and
      aberrant nerve branching were unchanged. CONCLUSION: Perhaps regenerating axons
      become misguided throughout the whole length of the nerve, not only at the site
      of the lesion, and strategies aimed at improving axon path-finding solely at the
      lesion site will therefore be inadequate.

PMID- 15854260
TI  - Stretch-associated injury in cervical spondylotic myelopathy: new concept and
      review.
AB  - The simple pathoanatomic concept that a narrowed spinal canal causes compression
      of the enclosed cord, leading to local tissue ischemia, injury, and neurological
      impairment, fails to explain the entire spectrum of clinical findings observed in
      cervical spondylotic myelopathy. A growing body of evidence indicates that
      spondylotic narrowing of the spinal canal and abnormal or excessive motion of the
      cervical spine results in increased strain and shear forces that cause localized
      axonal injury within the spinal cord. During normal motion, significant axial
      strains occur in the cervical spinal cord. At the cervicothoracic junction, where
      flexion is greatest, the spinal cord stretches 24% of its length. This causes
      local spinal cord strain. In the presence of pathological displacement, strain
      can exceed the material properties of the spinal cord and cause transient or
      permanent neurological injury. Stretch-associated injury is now widely accepted
      as the principal etiological factor of myelopathy in experimental models of
      neural injury, tethered cord syndrome, and diffuse axonal injury. Axonal injury
      reproducibly occurs at sites of maximal tensile loading in a well-defined
      sequence of intracellular events: myelin stretch injury, altered axolemmal
      permeability, calcium entry, cytoskeletal collapse, compaction of neurofilaments
      and microtubules, disruption of anterograde axonal transport, accumulation of
      organelles, axon retraction bulb formation, and secondary axotomy. Stretch and
      shear forces generated within the spinal cord seem to be important factors in the
      pathogenesis of cervical spondylotic myelopathy.

PMID- 15854261
TI  - A fantastic voyage: a personal perspective on involvement in the development of
      modern stereotactic and functional neurosurgery (1974-2004).
AB  - Stressing environments, individuals, ideas, and global events, this historical
      stereotactic and functional neurosurgical vignette initially presents a review of
      factors in the genesis of personal interest and the foundations of involvement in
      the discipline of neurological surgery. The vignette then traces the development
      of concepts and instrumentation and their ultimate practical utilization in
      patient care on the neurosurgical services at the Keck School of Medicine at the
      University of Southern California over the course of a 3-decade period (1974
      2004). The article summarizes and elaborates details of contributions to the
      literature and complex involvement on the national and international levels as
      the refinements and capabilities of stereotactic and functional neurosurgery have
      been reinvented over a generation through the emergence of new technology, ideas,
      individual ingenuity, and active collegial exchange.

PMID- 15854262
TI  - Neurosurgery at the Hadassah-Hebrew University Medical Center in Jerusalem.
AB  - Henrietta Szold founded the Hadassah Women's Organization in the United States in
      1912 to alleviate widespread disease and poverty in Jerusalem. In 1918, the
      Rothschild-Hadassah Hospital and the Hadassah School of Nursing opened in central
      Jerusalem. Chaim Weizmann and Albert Einstein, together with a small group of
      visionaries, founded the Hebrew University in 1923. After 1933, many physicians
      and scientists fled from Europe to Jerusalem, where they carried on their
      tradition of academic research at the university and Hadassah, and British
      military doctors joined medical rounds and lectures at Hadassah beginning in the
      1930s. Young physicians who had graduated from European medical schools were
      trained in the subspecialties at Hadassah beginning in the 1940s, and the Hebrew
      University-Hadassah Medical School enrolled its first class in 1949. These were
      the first academic institutions of their kind in Israel. The Department of
      Neurosurgery at Hadassah was established in 1941 under the leadership of Dr.
      Henry Wigderson, who was recruited from the United States. Dr. Aaron Beller
      became chairman in 1951, Dr. Mordechai Shalit became chairman in 1977, and Dr.
      Felix Umansky, the current chairman, was appointed in 1993. Today, more than 900
      neurosurgical procedures spanning the spectrum of subspecialties and using state
      of-the-art techniques and equipment are performed annually.

PMID- 15854263
TI  - A novel gene mutation (1292 deletion) in a Chinese family with cerebral cavernous
      malformations.
AB  - OBJECTIVE: Hereditary cerebral cavernous malformations (CCMs) are characterized
      by focal abnormalities of small blood vessels in the brain and consequent
      hemorrhage and seizures. Previous studies of this type of CCM have mainly
      reported on this disorder in Hispanic and Caucasian cases. Here, we report on
      hereditary CCM in a Chinese family further characterized by a novel CCM1 gene
      mutation. METHODS: We investigated a family of 21 members, of whom 3 died and 16
      of the survivors became the subjects of this study by brain magnetic resonance
      imaging. RESULTS: Brain magnetic resonance imaging demonstrated abnormal results
      in 11 members (69% penetrance), including multiple intracranial lesions in seven
      cases and single lesions in four cases. The clinical manifestation of CCM was
      found in these cases. The youngest patient was 4 years old. The remaining 5
      members were normal. Nucleotide sequencing analysis of the family member
      representing the index case and other affected members revealed a deletion
      frameshift mutation of A and T at nucleotides 1292 and 1293 in exon 13 of the
      CCM1 gene, which resulted in truncated encoding Krev interaction trapped-1
      protein. CONCLUSION: Our results indicated a novel hereditary CCM1 gene mutation
      of 1292delAT, a finding that may contribute to the clarification of the mechanism
      of the disease.

PMID- 15854264
TI  - Giant somatotrophinoma without acromegalic features: more "quiet" than "silent":
      case report.
AB  - OBJECTIVE AND IMPORTANCE: "Silent" somatotrophinomas are very rare, typically
      large pituitary adenomas that present with mild or no acromegalic features
      despite positive immunostaining for growth hormone and autonomous (nonglucose
      suppressible) growth hormone secretion. Because of this, they may be amenable to
      treatment with somatostatin analogues. CLINICAL PRESENTATION: We report a giant
      somatotrophinoma (7 cm in maximal diameter) in a young woman with 6 years of
      amenorrhea who had no clinical features of acromegaly despite frankly elevated
      serum insulin-like growth factor 1 level at the time of diagnosis.
      Immunohistochemistry revealed focal strong positive staining for growth hormone
      in only 10% of the surgical specimen. Mutations in exons 8 or 9 of GNAS1, which
      are present in 40% of somatotrophinomas, were absent in the surgical specimen.
      The patient's clinical, biochemical, and radiological presentation is described
      and is compared with previously reported cases of silent somatotrophinomas.
      INTERVENTION: Because of the size and visual symptomatology, partial resection
      was performed via a transcranial approach. External adjuvant beam radiotherapy
      was used. As insulin-like growth factor 1 levels remained elevated, treatment
      with somatostatin analogue is being pursued. CONCLUSION: This case represents one
      of the largest somatotrophinomas described to date, and it demonstrates that
      serum insulin-like growth factor 1 should be measured even in the absence of
      acromegalic features in patients presenting with apparently nonsecreting
      macroadenomas. In addition to surgery and radiotherapy, somatostatin analogues
      may play an important role in controlling tumor growth.

PMID- 15854265
TI  - Association of craniovertebral and upper cervical anomalies with dermoid and
      epidermoid cysts: report of four cases.
AB  - OBJECTIVE AND IMPORTANCE: Four patients with craniovertebral junction anomalies
      (CVJ) and Klippel-Feil cervical fusion defects associated with dermoid and
      epidermoid cysts are described. CLINICAL PRESENTATION: During the 10-year period
      from 1994 until May 2004, 435 patients with developmental CVJ anomalies presented
      to our institution. Four of these patients harbored a constellation of CVJ
      anomalies with dermoid and epidermoid cysts (hospital prevalence, 0.9%). All
      patients (ages 18, 23, and 25 yr) presented with features of spastic
      quadriparesis, restriction of neck movements, and raised intracranial pressure.
      Magnetic resonance imaging showed features of CVJ anomalies in all patients
      (occipitalization of C1, 3 patients; basilar invagination, 3 patients;
      atlantoaxial dislocation, 4 patients; and an abnormal posteriorly pointed dens, 1
      patient), along with a Klippel-Feil anomaly (Patients 1-3, 2nd and 3rd cervical
      vertebrae). Patient 4 also had a Chiari malformation with syrinx. In addition,
      all four patients had coexisting dermoid or epidermoid cysts (Patients 1 and 3,
      midline posterior fossa epidermoid; Patient 2, midline posterior fossa dermoid;
      Patient 4, quadrigeminal cistern epidermoid). INTERVENTION: Patients 1 and 2
      underwent a posterior midline approach, excision of the tumor, and an
      occipitocervical fusion (the atlantoaxial dislocation was reducible). Patient 3
      underwent transoral excision of the odontoid, followed by tumor excision and
      occipitocervical fusion via the posterior route. These patients had uneventful
      recovery. Patient 4 did not undergo an operation. CONCLUSION: Association of CVJ
      anomalies with Klippel-Feil and dermoid and epidermoid cysts is extremely rare,
      with only two previously reported cases. The patient who presented with a
      quadrigeminal cistern epidermoid with a craniovertebral junction anomaly and
      Chiari malformation with syrinx is the first such case ever reported in the
      literature. Apart from therapeutic implications, these patients may shed new
      light on the embryogenesis. Furthermore, the gathering of these manifestations
      may constitute components of a new syndrome that has gone unnoticed until now.

PMID- 15854266
TI  - Spontaneous spinal epidural hematoma during pregnancy: case report and literature
      review.
AB  - OBJECTIVE AND IMPORTANCE: Spinal epidural hematoma is a rare cause of spinal cord
      compression and acute para- or quadriplegia. Traumatic spinal epidural hematomas
      are usually seen in older men with a history of ankylosing spondylitis and
      vertebral fracture. Spontaneous spinal epidural hematomas are commonly associated
      with coagulopathies, tumors, or vascular malformations. There have been only five
      previously published case reports in the English-language literature of
      spontaneous spinal epidural hematomas in conjunction with pregnancy. CLINICAL
      PRESENTATION: We present the case of a 24-year-old woman at 20 weeks' gestation
      who presented to our service with a spontaneous cervicothoracic spinal epidural
      hematoma and complete quadriplegia. INTERVENTION: The patient was taken to the
      operating room for urgent surgical decompression and evacuation of the spinal
      epidural hematoma. CONCLUSION: The patient made a complete neurological recovery
      in long-term follow-up. In the meantime, she carried her pregnancy to term and
      gave birth to a healthy baby. Therefore, we advocate aggressive and early
      surgical intervention, similar to the five previously reported cases in the
      English-language literature, in the case of a spinal epidural hematoma causing
      cord compression and devastating neurological deficit in a pregnant woman.

PMID- 15854267
TI  - Symptomatic epidural hematoma caused by lumbar synovial cyst rupture: report of
      two cases and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: Juxtafacet cysts of the lumbar spine are a recognized
      cause of back pain, radicular symptoms, neurogenic claudication, and, less often,
      cauda equina compression syndrome. Hemorrhagic rupture of a juxtafacet cyst and
      the resulting epidural hematoma may cause chronic and/or acute cauda equina
      compression. CLINICAL PRESENTATION: We report two cases of ruptured hemorrhagic
      lumbar synovial cysts resulting in epidural hematoma and progressive symptomatic
      cauda equina compression. INTERVENTION: Surgical excision of the epidural
      hematoma and the associated cyst resulted in complete resolution of symptoms.
      CONCLUSION: Rarely, juxtafacet cysts of the lumbar spine may rupture and
      hemorrhage into the epidural space causing symptomatic cauda equina compression.
      It is important to consider this entity when evaluating the patient with cauda
      equina compression. The findings of these cases give insight into the clinical
      presentation, operative treatment, and outcome in these patients.

PMID- 15854268
TI  - Spontaneous resolution of acquired tonsillar herniation caused by isolated
      cerebellar tonsil inflammation: case report.
AB  - OBJECTIVE AND IMPORTANCE: Chiari I malformation is a well-known disease involving
      caudal descent of the cerebellar tonsils and is generally considered to be a
      congenital condition. Acquired Chiari I malformations as a result of various
      causes are well described. An unusual case is reported in which regression of an
      acquired Chiari I malformation caused by isolated cerebellar tonsil inflammation
      in a patient with infectious mononucleosis was observed after conservative
      treatment. This supports the view that the cause of tonsillar herniation should
      be considered as an important factor in patient selection for surgical
      decompression. CLINICAL PRESENTATION: A 6-year-old boy presented with a 1-week
      history of progressive occipital headache, neck pain, and dysequilibrium. A
      neurological examination revealed hyperreflexia in all extremities; he also had a
      fever, pharyngitis, and cervical adenopathy. A magnetic resonance imaging study
      demonstrated isolated right cerebellar tonsil enhancement and herniation into the
      foramen magnum. Further laboratory findings disclosed Epstein-Barr virus
      infection. INTERVENTION: The patient underwent conservative treatment for
      systemic illness, and he was asymptomatic after 3 weeks. A follow-up magnetic
      resonance imaging study obtained 2 months after discharge demonstrated resolution
      of the tonsillar herniation. CONCLUSION: Because the patient presented with
      infectious mononucleosis and cerebellar tonsillar herniation, direct treatment of
      decompression was considered unnecessary. Thus, caution in patient selection for
      surgical treatment is suggested in such unique cases.

PMID- 15854269
TI  - Vertebral artery-to-middle cerebral artery bypass with coil embolization of giant
      internal carotid artery aneurysm: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Cerebral revascularization with extracranial-to
      intracranial bypass is often required during the surgical treatment of complex
      intracranial aneurysms. This report is the first in which a vertebral artery (VA)
      to-middle cerebral artery (MCA) bypass in conjunction with endovascular coil
      embolization is used in the successful treatment of a giant intracranial
      aneurysm. CLINICAL PRESENTATION: A 68-year-old man previously diagnosed with a 6
      cm internal carotid artery (ICA) aneurysm presented complaining of progressing
      left hemiparesis and mental status changes. His aneurysm had been treated
      previously by common carotid artery occlusion 20 years earlier. Arteriography
      defined the partially thrombosed, right supraclinoid ICA aneurysm arising at the
      junction of the posterior communicating artery and the supraclinoid ICA.
      INTERVENTION: Because of the patient's worsening symptomatology, endovascular
      coiling with placement of a superficial temporal artery-to-MCA bypass was
      performed. The patient tolerated this procedure well, and his symptoms resolved.
      However, they recurred several months later, and imaging suggested poor right
      hemispheric perfusion despite a patent bypass. A VA-MCA bypass using a saphenous
      vein graft was then performed using the distal right VA at the level of cervical
      vertebra 1 (C1) as the donor vessel with a distal anastomotic site on the right
      MCA. Coil embolization of the aneurysm was repeated, and the feeding posterior
      communicating artery was sacrificed. The patient is currently asymptomatic more
      than 1 year after the second bypass and coil embolization. CONCLUSION: This
      report describes a safe and definitive treatment option for a giant intracranial
      ICA aneurysm using a posterior-to-anterior circulation (VA-MCA) bypass, followed
      by endovascular coil embolization in a patient with previous ligation of the
      common carotid artery. VA-MCA high-flow saphenous vein bypass followed by coil
      embolization is a useful technique that is especially valuable in the subset of
      giant aneurysm patients who have previously been treated by carotid ligation.

PMID- 15854270
TI  - Near-miss injection of an anesthetic agent into a cerebrospinal fluid external
      ventricular drain: special report.
AB  - OBJECTIVE AND IMPORTANCE: Human error has been increasingly recognized as a cause
      of patient morbidity and mortality. One method of error prevention is the
      reporting of a near-miss event. We report that intravenous anesthetic agents were
      nearly injected into the external ventricular drainage (EVD) of a patient during
      an emergency shunt procedure. CLINICAL PRESENTATION: A 3-year-old male patient
      with multiple cerebrospinal fluid shunts and shunt infection had an external
      ventricular drain catheter tunneled to exit just inferior to the left clavicle
      during a previous procedure. The exit site was covered by an occlusive dressing.
      This particular system, the Codman external drainage system II collection bag and
      tubing set (Codman & Shurtleff, Inc., Raynham, MA), contains two access ports (a
      three-way stoppered port and an angled rubber stoppered injection port). At
      induction of anesthesia, the EVD system was mistaken for a central venous line
      and was nearly injected with propofol and rocuronium. Fortunately, the error was
      quickly recognized and the patient came to no harm. INTERVENTION AND TECHNIQUE: A
      modified EVD system has recently been released that does not include the three
      way port, and features an embedded bright green stripe in the tubing to
      distinguish it from intravenous tubing. CONCLUSION: We recommend using caution
      when tunneling EVDs to sites that might be confused with central venous access
      sites. EVD system tubing should be designed so it can be easily distinguished
      from intravenous tubing, and it should be clearly labeled as an EVD line.

PMID- 15854271
TI  - [Present status in studying immunotherapy for acute leukemia and its perspective-
      Editorial].
AB  - One of the important approaches for further prolonging remission duration and
      eradicating minimal residual disease in acute leukemia is immunotherapy. Four
      kinds of immunotherapy for acute leukemia are under investigation: (1) monoclonal
      antibodies, among them, Mylotarg (cytotoxic antibiotic calicheamicin linked to
      CD33 Mab) is given for the treatment of refractory or relapsed acute myeloid
      leukemia and molecular relapse in acute promyelocytic leukemia with good results,
      Campath-1H (antiCD52 Mab) is administered in the treatment of prolymphocytic
      leukemia and Rituximab (anti-CD20 Mab) in B-PLL with high complete remission
      rates. Other Mabs under preclinical and clinical trials include anti-IL-2
      receptor Mab for the treatment of acute T lymphocytic leukemia, anti-220 kD Mab
      6G7 for acute leukemias, recombinant immune toxin BL22 (anti-CD22) for hairy cell
      leukemia and Mabs labeled with radio-isotopes for different types of acute
      leukemias; (2) adoptive cellular immunotherapy using cytokine-induced killer
      cell, alloreactive NK cells, allogeneic or autologous leukemic-specific CD8(+)
      cytotoxic T lymphocytes, and other immune effector cells; (3) cytokines and other
      immune modulators comprising IL-2, IL-12, GM-CSF, CD40L, FLT-3L and thalidomide
      and its derivatives; (4) leukemia vaccines of several different formulations
      including antigen-specific, leukemia cell-based, leukemia antigen-pulsed
      dendritic cell (DC) and leukemia-derived DC vaccines, the latter two formulations
      are more attractive. In conclusion, up to now, the most effective example of
      immunotherapy in acute leukemia is provided by the administration of Mabs, and
      the majority of other approaches in immunotherapy for acute leukemia although
      promising, need further studies.

PMID- 15854272
TI  - [The mechanisms of p21WAF1/Cip-1 expression in MOLT-4 cell line induced by TSA].
AB  - To investigate the function and molecular mechanism of p21(WAF1/Cip-1) expression
      in MOLT-4 cells induced by HDAC inhibitor TSA, the expression pattern of
      p21(WAF1/Cip-1) and the distribution of cell cycle in TSA treated cells were
      analyzed. The results showed that TSA could effectively induce G(2)/M arrest and
      apoptosis of MOLT-4 cells. Kinetic experiments demonstrated that p21(WAF1/Cip-1)
      were upregulated quickly before cell arrested in G(2)/M and began decreasing at
      the early stage of apoptosis. Meanwhile, the proteasome inhibitor MG-132 could
      inhibit the decrease of p21(WAF1/Cip-1) at the early stage of apoptosis, which
      showed that proteasome pathway involved in p21(WAF1/Cip-1) degradation during the
      TSA induced G(2)/M arrest and apoptosis responses. This study also identified
      that the protein level of p21(WAF1/Cip-1) was highly associated with the cell
      cycle change induced by TSA. Compared to cells treated by TSA only, exposure MOLT
      4 cells to TSA meanwhile treatment with MG-132 increased the protein level of
      p21(WAF1/Cip-1) and increased the numbers of cell in G(2)/M-phase, whereas the
      cell apoptosis were delayed. It is concluded that p21(WAF1/Cip-1) plays a
      significant role in G(2)/M arrest and apoptosis signaling induced by TSA in MOLT
      4 cells.

PMID- 15854273
TI  - [GFP fused to the cytoplasmic tail of integrin alphaIIb allows the normal
      expression of alphaIIb beta3 compound in CHO cells].
AB  - To investigate the effect of GFP fused to C terminal of integrin alpha(IIb) on
      the biosynthesis and expression of alpha(IIb) beta(3) compound, the alpha(IIb)
      GFP expression plamid, named palpha(IIb) GFP, the cDNA of alpha(IIb) was
      constructed from p3.1-2b and fused to pEGFP-N1 in frame. When the sequence of
      palpha(IIb) GFP was confirmed by sequencing it was transferred to Chinese Hamster
      Ovary (CHO) cells with or without p3.1-3a expressing integrin beta(3). Then the
      expression of alpha(IIb) GFP fusion protein was confirmed by Western blot and
      then its subcellular localization was determined with laser confocal scanning
      microscopy. The results showed that the target gene was cloned into recombinant
      vector by restriction analysis and sequencing. Overexpression of the fusion
      protein in the transfected CHO cells was identified with Western blot.
      Subcellular localization analysis confirmed that alpha(IIb) GFP was expressed in
      CHO cells and could be transferred from endoplasmic reticulum to Golgi apparatus.
      It is concluded that the eukaryotic expression plasmid containing alpha(IIb) GFP
      fusion gene is successfully constructed. GFP fused to the cytoplasmic tail of
      integrin alpha(IIb) allows the normal expression of alpha(IIb) beta(3) in CHO
      cells.

PMID- 15854274
TI  - [Analysis of the methylation in the promoter of LRP15 gene and its expression].
AB  - To study the methylation in the promoter of LRP15 gene and its relationship with
      gene expression and to explore the possible mechanism of regulating LRP15 gene
      methylation, the methylation in the promoter of LRP15 gene in K562 cell line was
      detected by MS-PCR. Then K562 was exposed to 5-aza-2'-deoxycytidine (CdR) and
      trichostatin (TSA), to determine whether the silencing of LRP15 gene by de novo
      methylation could be reversed. As a result, it was confirmed by MS-PCR that the
      promoter of LRP15 was hypermathylated in K562 cell line, and lost its
      transcription activity. After CdR, with or without TSA, the silencing of LRP15
      gene by de novo methylation can be reversed. Observation demonstrated that the
      expression of LRP15 was controlled by methylation in its promoter in K562. It is
      suggested that methyltransferase inhibitor and deacetylase inhibitor may be
      effective agents in leukemia therapy.

PMID- 15854275
TI  - Anti-CD47 monoclonal antibody (B6H12) impairs the maturation and function of
      human dendritic cells.
AB  - To investigate the influence and mechanisms of CD47 engagement by its soluble mAb
      B6H12 on the maturation and function of cultured dendritic cells (DCs), monocyte
      derived DCs were propagated in granulocyte-macrophage colony stimulating factor
      (GM-CSF) combined with lipopolysaccharide (LPS) and interleukin (IL)-4, in the
      presence or absence of soluble anti-CD47 monoclonal antibodies (anti-CD47 mAbs,
      B6H12). The characteristic morphology of DCs was identified by using the
      transmission electron microscopy. Flow cytometry was used to detect the cell
      surface phenotypes. The concentration of IL-12 P70 in supernatant was measured by
      ELISA. The antigen-presenting functions of DCs were determined in one-way mixed
      leukocyte reaction by BrdU-ELISA. Electrophoretic mobility shift assay (EMSA) was
      applied to examine the activity of NF-kappaB. The results indicated that the anti
      CD47 mAbs markedly suppressed the expression of CD80, CD86, CD83, CD1a and HLA-DR
      on the surface of DCs (P < 0.05). The data of the mixed leukocyte reaction and IL
      12 P70 production were consistent with the results by flow cytometry (P < 0.01).
      Pre-exposure to B6H12 mAb during the development of DCs resulted in a dramatic
      depletion of the DNA binding activity of NF-kappaB toward nucleus protein.
      Moreover, such an inhibition effect seemed to be dose dependent. In conclusion,
      the soluble mAb B6H12 inhibits the expression of the costimulatory molecules and
      MHCII molecules on the DCs. The antigen-presenting function of DCs was also
      impaired by B6H12. And these modulations are closely related with the depletive
      DNA binding activity of NF-kappaB. It is suggested that the soluble B6H12 exerts
      a negative effect on the maturation and function of in vitro cultured DCs due to
      inhibition of NF-kappaB binding activity.

PMID- 15854276
TI  - Expansion in vitro and cytotoxicity of dendritic cells from patients with chronic
      myeloid leukemia.
AB  - The study was aimed to investigate the extensive amplification and the
      cytotoxicity of dendritic cells (DC) derived from chronic myeloid leukemia cells.
      DC were cultured in two steps: firstly, extensive amplification in primary
      culture of CD34(+) or mononuclear cells isolated from CML patients' bone marrow
      and peripheral blood with rhFlt3-L and rhTPO for 7 days; secondly, inducing
      culture of DC with rhGM-CSF, rhTNF and rhIL-4 for 14 days. A system inducing DC
      directly were established for comparison. DC were identified by immunophenotype
      with flow cytometry, chromosome analysis by displaying G banding and electric
      microscopy analysis. The function of stimulating T cells proliferation and
      cytotoxicity of CML cells were confirmed through MTT assay. The results showed
      that after first extensive amplification in primary culture with rhFlt3-L and
      rhTPO for 7 days, CD34(+) cells had a total cell number with (77 +/- 5) fold
      expansion, and DC were (39 +/- 8)% of total cell respectively after induction
      culture of DC with rhGM-CSF, rhTNF and rhIL-4 for 14 days. Both the amplification
      of cell number and yield of DC were higher than the system without extensively
      culture (P < 0.01). Such DC could stimulate T cells to proliferate and kill
      leukemia cells finally. In conclusion, two-step culture method can obviously
      improve the cell number of DC required, that is better than inducing them
      directly. DC derived from CML cells induce the generation of anti-leukemia
      immunization.

PMID- 15854277
TI  - [Application of immunomagnetic screening strategy for separation of CD4+ and CD8+
      T cell subpopulations of peripheral blood].
AB  - To evaluate the separation of T lymphocyte subsets by immunomagnetic beads and to
      find optimization of strategy for specific binding of antibody-coated beads to
      cells, two strategies to isolate enriched T lymphocyte subpopulation CD4+ T cells
      and CD8+ T cells from small volumes (< 5 ml) of peripheral blood by using
      immunomagnetic beads or complement cytotoxicity method were compared. The purity
      and activity of CD4+ T cells and CD8+ T cells were measured by using flow
      cytometry, trypan-blue dye exclusion test, etc. The results showed that the
      yields of CD4+ T lymphocytes and CD8+ T lymphocytes by using immunomagnetic beads
      were (94.2 +/- 1.4)% and (93.8 +/- 3.0)% respectively, higher than those of
      control group and the group of using completement cytotoxicity method (P < 0.05).
      At the same time, the yields of CD4+ T lymphocytes and CD8+ T lymphocytes by
      using complement cytotoxicity method were (76.0 +/- 2.8)% and (77.0 +/- 3.0)%
      respectively, higher than those of unenriched group (P < 0.05). The trypan-blue
      dye exclusion test confirmed that there were no influences on activity of CD4+ T
      cells and CD8+ T cells when immunomagnetic beads were used for separation of
      these cells from peripheral blood. It is concluded that the immunomagnetic bead
      method has a higher efficiency for separation of CD4+ T cells and CD8+ T cells
      from peripheral blood than complement cytotoxic method, especially for small
      sample. This method has no influence on activity and proliferation of T
      lymphocyte subpopulations, and would be expected to establish conditions for
      research of biological characteristics of CD4+ T cells and CD8+ T cells in
      future.

PMID- 15854278
TI  - [Study on the correlation between acute lymphoblastic leukemia and HLA genes in
      southern China Han population].
AB  - To study the correlation between acute lymphoblastic leukemia (ALL) and HLA-A, B
      and DRB1 gene in southern Chinese Han population and to investigate the
      susceptible HLA gene to ALL, a total of 4707 healthy volunteer bone marrow donors
      from southern Chinese Han population were used as a control group, 201 patients
      diagnosed as patient group from southern Han individuals were genotyped at HLA-A,
      B and DRB1 loci by PCR-SSP, PCR-SSOP and SBT. HLA allele frequency and its
      distribution of ALL patient group were compared with the control group by using
      chi(2) test, and calculated the statistic value of relative risk (RR),
      pathogenicity score (EF) and preventive score (PF). The results showed that in
      comparison with the control group, the gene frequence of HLA-A26, B56 and DR9
      increased significantly, but the gene frequence of HLA-A30, A33 and B58 allele
      frequency decreased significantly for patients with ALL. It is concluded that HLA
      A26, B56 and DR9 gene have a high correlation with ALL and seem to contribute the
      genetic susceptibility to ALL in southern Chinese Han populations. However, HLA
      A30, A33 and B58 gene seem to have protective role for southern Han individuals
      suffered from ALL.

PMID- 15854279
TI  - [Polymorphism of HLA-B* 40 gene family in Chinese Han population].
AB  - To investigate the allele distribution of HLA-B* 40 gene family in Chinese Han
      population and to study its influence on the selection of clinical
      transplantation donor, the HLA-B genetypes of 381 individuals randomly selected
      from Chinese National Marrow Donor Project were identified by PCR-SSO, and then
      all the HLA-B* 40 positive samples from the above population and the B* 40
      homozygote samples received from another 1 270 registered donors were analyzed by
      PCR-SBT and PCR-SSP at high resolution. The results showed that the population of
      381 registered donors was examined at HLA-B locus by using Hardy-Weinberg
      equilibrium, the gene frequency of HLA-B* 40 was 0.1692. Four different HLA-B* 40
      alleles (B* 4001, B* 4002, B* 4003, B* 4006) were identified, and the serological
      specificity was B60 and B61 respectively. The relative frequency of each allele
      was 0.1192 for B* 4001, 0.0154 for B* 4002, 0.0038 for B* 4003, 0.0308 for B*
      4006. The distribution of B* 40 homozygote revealed a certain regularity at high
      resolution, B* 40XX (B* 4001 group), at low-resolution; B* 4001 at high
      resolution; B* 40XX (B* 4002 group), at low-resolution; B* 4002 or B* 4006 or
      heterozygote of both at high-resolution. It is concluded that in Chinese Han
      population, predominant allele in HLA-B* 40 gene family is B* 4001, the high
      resolution typing may be recommended to use for the selection of clinical
      transplantation donor.

PMID- 15854280
TI  - [Sequence analysis of 3'-non-coding region of RHD].
AB  - There are 3' non-coding region, downstream Rhesus box, SMP1 gene et cetera. after
      RHD stop code. This study was intended to determine the sequence of 3' non-coding
      region. One pairs of primer was designed and then a polymerase chain reaction
      (PCR) was established for specific amplification of whole length of 3' non-coding
      region of RHD in 10 Rh-positive and 10 D(el) samples. The PCR products were
      purified and directly sequenced. The results showed that all Rh-positive and
      D(el) samples were identical, which revealed that there were 103 bp between 3'
      end of RHD coding region and 5'-end of downstream Rhesus box. The D(el) samples
      showed the same result with the normal Rh-positive sample. It suggests that lower
      expression of D antigen in D(el) red cells does not associate with 3' non-coding
      region of D(el) gene.

PMID- 15854281
TI  - [Differentiation from human embryonic stem cells to hematopoietic cells and
      endothelial cells].
AB  - Embryonic stem cells are pluripotent and their differentiation in vitro can serve
      as an experimental model to explore the molecular mechanisms of early embryonic
      development. To investigate the effect of stromal cell conditioned medium
      combined with cytokines (sccm + cys) on the differentiation from human embryonic
      stem cells to hematopoietic cells and endothelial cells, the mouse fibroblast
      feeder cells to make human embryonic stem cells grown into embryonic bodies (EBs)
      were initially deleted. After culture for 3 days, EB cells were trypsinized into
      single cells and induced for 8 days by sccm + cys. Then, the differentiated cells
      were cultured in the semisolid medium containing 0.9% methylcellulose and
      cytokines to study the colony forming and self-renewal ability of cells.
      Immunocytochemical staining was used to check the surface markers of the colony
      cells. During the induction, mRNA expression of flk-1, BMI-1, scl, and Zeta
      globin genes was tested by RT-PCR. Surface markers, such as flk-1, CD34 were
      tested by the flow cytometry. The results demonstrated that: (1) cell clusters
      containing 20-30 cells were formed after culture for 8 - 14 days in the semisolid
      medium, replanting these cells resulted in similar cell cluster forming. In
      addition, CD45 positive in big cell colonies were also found in the semisolid
      medium; (2) attached cell colonies appeared after culture for 8 days in the
      semisolid medium and VIII factor, UEA and KDR could be detected as negative by
      immunocytochemical staining; (3) on the 4(th) day of induction, mRNAs of flk-1,
      BMI-1, scl and Zeta-globin were all expressed. On the 8(th) day of induction, all
      of the above genes except Zeta-globin were expressed, while ES cell and EB cells
      which served as controls did not express scl and Zeta-globin genes; (4) on the
      8(th) day of induction, the proportions of flk-1(+) cells and CD34(+) cells among
      all the inducing population were 9.8% and 16.8%, respectively, while the
      corresponding positive populations were 0.36% and 1.16% in spontaneously
      differentiated 11(th) day's EB, and 0.04% and 0.16%, respectively, in ES cells.
      If is concluded that embryonic stem cells can differentiate into hematopoietic
      cells and endothelial cells in combinant culture system of this study.

PMID- 15854282
TI  - [Proliferation and apoptosis in vitro of umbilical cord blood CD34+CD38-
      hematopoietic early progenitor cells].
AB  - To cultivate CD34(+)CD38(-) cells isolated from umbilical cord blood of healthy
      puerperal women over a longer-period of time for observation of cell division,
      proliferation, apoptosis, and effects of stem cell factor on the growth of
      CD34(+)CD38(-) cells, with flow cytometry, CD34(+)CD38(-) cells were isolated
      from umbilical cord blood of 10 healthy puerperal women and cultivated in stem
      cell media with supplement of IL-3, IL-6, GM-CSF, EPO, IGF-1 and SCF 6 kinds cell
      growth stimulating factors for six months. The cell growth curves were
      established. The effects of stem cell factor on the growth of CD34(+)CD38(-)
      cells and cell apoptosis were investigated with the single cell gel
      electrophoresis technique and flow cytometry method, respectively. The results
      showed that CD34(+)CD38(-) cells isolated from umbilical cord blood were capable
      of proliferating after being cultivated in vitro over a longer-period of time
      with no evidence of the presence of excessive apoptosis. In conclusion, under
      appropriate culture conditions, CD34(+)CD38(-) hematopoietic early progenitor
      cells from umbilical cord blood can serve as a resource providing a large amount
      of primitive cells for transplantation therapy after a longer period of
      cultivation and proliferation in vitro.

PMID- 15854283
TI  - [Expansion ex vivo of human bone marrow mesenchymal stem cells and cord blood
      CD34+ cells].
AB  - The aim was to study the roles that the bone marrow mesenchymal stem cells (MSC)
      and cytokines play in cord blood CD34(+) cell expansion ex vivo and the influence
      of culture ex vivo on expression of the adhesive molecule of CD44. CD34(+) cells
      sorted from cord blood cells had been cultured in each well of 24 well culture
      plates containing culture medium supplemented with mesenchymal stem cells layer
      or/and cytokines for a week, and then all kinds of indexes of different groups
      were compared. The results showed that as for cord blood cell expansion, there
      was no significant difference between the groups with cytokines SDF-1alpha + SCF
      + TPO + FL and SCF + TPO + FL no matter if MSC layer existed or not. The groups
      with MSC layer and cytokines were superior to the corresponding groups without
      MSC layer. In addition, the expression of the adhesion molecule CD44 had no
      distinct change after culture. It is concluded that SDF-1alpha has no distinct
      influence on the effect of cytokines SCF + TPO + FL on cord blood cell expansion
      ex vivo. MSC enhance the effect of cytokines on cord blood cell expansion ex
      vivo. Such expansion ex vivo may not influence the expression of the adhesive
      molecule CD44 on cord blood cells.

PMID- 15854284
TI  - [Retrospective analysis of 54 cases of unrelated umbilical cord blood
      transplantation].
AB  - In order to research the related factors of umbilical cord blood transplantation,
      54 cases of unrelated umbilical cord blood transplantation were analyzed
      retrospectively, which were performed from June 1998 to July 2003. All cord blood
      units were obtained from full term normal vaginal deliveries in Guangzhou
      Maternal-Neonatal Hospital. The fractionation, cryopreservation and thawing of
      cord blood have been done according to the regulation of New York umbilical cord
      blood bank and pertinent literature. The selection of cord blood is based on HLA
      typing and the number of nucleated cells. The results showed that from June 1998
      to July 2003, 3 475 units of cord blood were collected in Guangzhou Umbilical
      Cord Blood Bank and 99 units were provided for therapy of 85 patients in 21
      transplantation centers, including 11 sibling and 74 unrelated cord blood
      transplantations. 54 cases of unrelated cord blood transplantation were reported,
      including 43 malignant diseases and 11 non-malignant diseases. The median age of
      recipients was 9.5 (range 1.2 - 33) years, the median weight was 27 (range 10 -
      60) kg, the median number of TNC was 6.82 x 10(7)/kg, 43 cord blood were
      implanted (ANC > 500/microl) at day 60 after transplantation (79.6%, median 17).
      The time of nuclear cell reconstitution after cord blood transplantation was
      statistically related with nucleated cells and the type of disease, not related
      with HLA matching. Acute GVHD was present in 8 patients (21.6%) and chronic GVHD
      occurred in 2 patients (5.4%), 6 patients suffered from graft failure (11.1%).
      The total survival rate was 42.6%. It is suggested that unrelated umbilical cord
      blood transplantation seems to be a good substitute for bone marrow
      transplantation and has good prospects especially in children.

PMID- 15854285
TI  - [Comparison of the effect of Cobe Spectra and Fenwal CS 3000 plus blood cell
      separators in collection of peripheral blood stem cell components].
AB  - To evaluate the hematopoietic stem/progenitor cell apheresis effect of Cobe
      Spectra (Version 6.1) and Fenwal CS 3000 Plus cell separators, fourty-two
      procedures on twenty donors using Cobe Spectra cell separator and twenty-two
      procedures on sixteen donors using Fenwal CS 3000 Plus cell separator were
      retrospectively analyzed. The number of CD34(+) cells collected, the collection
      efficiency (CE) of CD34(+) cells and the contaminations of red blood cell and
      platelet in the stem/progenitor cell products of two devices were compared. The
      results showed that there were no significant differences in the total number of
      CD34(+) cells collected and the CD34(+) cell CE between the two devices. There
      were positive correlations between the count of peripheral blood cells including
      leukocyte, monocyte, hematopoietic progenitor cell and CD34(+) cell after
      mobilization and the total number of CD34(+) cells collected. The stepwise
      multiple variable analyses revealed the peripheral blood stem/progenitor cell
      count emerged as the only significant independent predictive factor for CE. A
      negative correlation was seen between the peripheral blood monocyte count and the
      CD34(+) cell CE for the Fenwal CS 3000 Plus. The Fenwal CS 3000 Plus product
      contained more red blood cells than that of the Cobe Spectra. The decrease in the
      peripheral platelet count after Fenwal CS 3000 Plus apheresis was also greater.
      It is concluded that collection efficacy of Cobe Spectra (Version 6.1) and Fenwal
      CS 3000 Plus was similar. Cobe Spectra shall be used preferably to assure higher
      CD34(+) cell CE at a high peripheral blood monocyte count. The Cobe Spectra cell
      separator is better for the donors with mismatched blood type and the donors with
      thrombocytopenia.

PMID- 15854286
TI  - [Immunophenotypes in 115 patients with acute myeloid leukemia by multi-color flow
      cytometry].
AB  - Immunophenotyping has become common in the diagnosis and classification of
      leukemia. To evaluate the immunophenotype of acute myeloid leukemia (AML),
      multiparameter flow cytometry and CD45/SSC gating were used to analyze the
      surface and cytoplasmic antigen expressions in 115 cases of AML. The results were
      compared with the French-American-British (FAB) Cooperative Group classification
      to help define the best use and role of multiparameter flow cytometry in the
      diagnosis and proper classification of AML. The results showed that CD38, CD38
      and CD13 were the most commonly expressed antigen (94.8%, 91.3% and 89.6%,
      respectively). CD7 was the most commonly expressed lymphoid antigen (20.2%),
      followed by CD19 (16.5%) and CD2 (15%). Some immunophenotypes correlated with FAB
      type, including increased frequency of CD2 in M(3); lack of HLA-DR, CD34 and CD56
      expression in M(3); increased frequency of CD19 in M(2), CD14 and CD56 in M(5)
      and lack of MPO in M(0). In conclusion, multiparameter flow cytometry is a
      reliable technique in the diagnosis of AML, and some immunophenotypes correlate
      with FAB type.

PMID- 15854287
TI  - [Expression of cyclin g2 mRNA in patients with acute leukemia and its clinical
      significance].
AB  - To evaluate the expression of cyclin G2 mRNA in patients with acute leukaemia
      (AL) and its clinical value, the expression of cyclin G2, G1 and P53 mRNA in the
      bone marrow from 74 AL patients and 10 normal individuals as control were
      detected with reverse transcription polymerase chain reaction (RT-PCR). The
      positive segment of cyclin G2 was analyzed by DNA sequencing. The results showed
      that (1) the positive rate and the expressing level of cyclin G2 in AL patients
      (52.7%, 0.552 +/- 0.498) were significantly lower than those in normal control
      (100%, 1.953 +/- 0.675) (P < 0.01); (2) among new diagnosed AL patients, the
      complete remission (CR) rate (69.2%) in the positive cyclin G2 patients was
      higher than that (40%) in negative cyclin G2 patients (P < 0.05); (3) the
      positive rate of cyclin G2 (43.6%) in resistance group was significantly higher
      than that (68.6%) in sensitive group (P < 0.01); (4) following-up for 14.3 month
      (11 - 18.5 month) in 28 AL patients with CR, there were 10 relapsed in 11 AL
      patients with low expression level of cyclin G2 (90.9%); and 7 relapsed in 17 AL
      patients with high expression (41.2%), and there was significant difference (P <
      0.05). In conclusion, the expression of cyclin G2 in AL patients was higher than
      that in normal control, the abnormal expression of cyclin G2 might be a
      prognostic marker of CR in AL patients.

PMID- 15854288
TI  - [Clinical significance of the expression of DNA methyltransferase genes (DNMT) in
      acute leukemia patients].
AB  - To investigate the relationship between the expression of DNMT and clinical
      prognosis in adult patients with acute leukemia (AL), the mRNA expressions of
      DNMT, p15(INK4B), mdr1 were measured in 72 AL patients and 20 normal controls by
      semi-quantitative reverse transcription polymerase chain reaction (RT-PCR); the
      ratio of p15 CpG land methylation was measured in 56 AL patients and 14 normal
      controls by methylation-specific PCR (MSP-PCR). The results showed that all three
      DNMT mRNA expressions in AL patients were significantly higher than that in
      normal controls (P < 0.01). When the internal control was changed into PCNA, a
      kind of cell proliferation marker gene, the difference still showed a statistic
      significance. All three DNMT genes were significantly expressed and positively
      correlated with AL patients, showing high synergistic expression, and there was a
      negative correlation between the levels of p15, mdr1 gene expression and DNMT.
      The complete remission (CR) rate in AL patients with the positive expression of
      all DNMT genes was significantly higher than that of AL patients with partially
      positive or negative expression (P < 0.01) of DNMT genes. In 56 AL patients, the
      P15I(NK4B) was completely methylated in 55.4% (31 of 56), partly methylated in
      21.4% (12 of 56) and all 14 cases of normal controls were not methylated. It is
      concluded that DNMT genes are abnormally high expressed in adult AL patients,
      which lead to methylation-silence of tumor suppressor genes by CpG land
      hypermethylation, the AL patients with high expression of DNMT are more sensitive
      to chemotherapy, which may be a good prognostic factor for AL patients.

PMID- 15854289
TI  - [Sensitivity of survivin-positive primary leukemia cells to chemotherapy].
AB  - To explore the sensitivity of survivin-positive primary acute leukemia (AL) cells
      to various chemotherapeutics, RT-PCR was used to detect the expression of
      survivin mRNA in AL cells, the cytotoxicity of chemotherapeutics was investigated
      with the MTT assay. The results indicated that for the primary AL cells cultured
      with various chemotherapeutics for 15 hours, the cytotoxicities of daunorubicin
      (DNR), homoharringtonine (HHT), aclacinomycin (Acla), Ara C (cytosine
      arabinoside), HA (HHT + Ara C), DA (DNR+Ara C) to the survivin-positive AL cells
      were similar with that to the survivin-negative AL cells. When AL cells were
      treated with AA (Acla + Ara C) in vitro, the cytotoxicity in survivin-positive
      group was apparently higher than that in survivin-negative group [(37.24 +/-
      18.36)% vs (24.32 +/- 9.33)%, P = 0.032]. It is suggested that the survivin
      positive AL cells may be sensitive to some chemotherapy, such as AA (Acla + Ara
      C).

PMID- 15854290
TI  - [Influence of anti-CXCR4 monoclonal antibody 12G5 on killing effect of cytosine
      arabinoside to HL-60 cell].
AB  - This study was aimed to explore the influence of anti-CXCR4 monoclonal antibody
      12G5 on killing effect of cytosine arabinoside (Ara C) to HL-60 cell, and to
      assess its therapeutic value in marrow residual disease. HL-60 cells were
      cultured and co-cultured with leukemic stromal cells, and SDF-1 activity was
      inhibited with 10 microg/ml 12G5, then, killing effects of Ara C on HL-60 cells
      were investigated by MTT and morphology assay. Curves by MTT assay revealed that
      in the test group of 20 microg/ml Ara C, A(540) values decreased slowly but
      straightly, however, in control group A(540) values decreased markedly for the
      first two days, and increased from day 3 or 4. In the test group of 40 microg/ml
      Ara C, although increasing at constricted range of 7 - 9 days, A(540) values
      decreased in whole observing period of 12 days, while in control group A(540)
      values decreased markedly at day 0-3, and increased from day 4. Furthermore, two
      curves go across each other at day 5, and continue the increasing tendency.
      Morphology results showed that in both treated groups, the number of HL-60 cell
      decreased markedly and increased gradually in control group, but just contrary to
      test group. It is concluded that 12G5 may weaken the killing effect of Ara C on
      HL60 cell in earlier period, but reinforce the total killing effect and delay the
      occurrence of drug resistance simultaneously. Thus 12G5 has the therapeutic
      potential on marrow residual disease.

PMID- 15854291
TI  - [Expression of stromal cell derived factor-1(SDF-1) and its receptor CXCR4 in
      hematologic malignancies].
AB  - The aim was to analyze the expression level of stromal cell derived factor-1 (SDF
      1) and its functional chemokine receptor CXCR4 in the patients with hematologic
      malignant tumor and their clinic significance. 28 patients with hematologic
      malignant tumor and 12 normal controls were chosen to be experimental objects.
      CXCR4 expressed on the cell membrane in bone marrow was enumerated by flow
      cytometry and serum level of SDF-1 was determined by ELISA assay. The result
      showed that the expression of SDF-1 and CXCR4 in hematologic malignant tumor were
      higher than that in normal controls, and the expression levels of two molecules
      were correlated. What is more, the different hematologic malignant tumor had
      different CXCR4 expression. In conclusion, the high expression of SDF-1 and CXCR4
      in serum and bone marrow cells can be used as detective factors to hematologic
      malignant tumor. A correlation exists between the high expression of CXCR4 and
      the infiltration of hematologic malignant cells.

PMID- 15854292
TI  - [Study on NB4 cell apoptosis induced by trichosanthin].
AB  - In order to study the influence of trichosanthin (TCS) on apoptosis and growth
      inhibition of human NB4 cells in vitro, the expression of annexin V and the
      change of DeltaPsim of NB4 cells induced by TCS was analyzed by FACS, and MTT
      assay was adopted to measure the growth inhibition ratio of NB4 cells treated
      with TCS. Apoptosis was assayed by agarose gel electrophoresis. The results
      showed the higher concentration of TCS and the longer the acting time, the
      stronger growth inhibition of NB4 cells. The expression of annexin V was
      positive, and the positive ratio was greatly enhanced with prolongation of acting
      time. DeltaPsim reduced gradually while the apoptosis cells increasing. DNA
      agarose gel electrophoresis showed a gradient, which confirmed that TCS could
      induce NB4 cells apoptosis. In conclusion, taken together, data show that TCS can
      inhibit NB4 growth in vitro, and induce apoptosis. Experiment provides an
      important evidence for application of TCS in clinical treatment of acute
      promyelocytic leukemia.

PMID- 15854293
TI  - [Influence of cytochrome C on apoptosis induced by daunorubicine in acute myeloid
      leukemia (AML) cells].
AB  - The purpose was to study the responses of AML cell treated with cytochrome C and
      to explore the influence of cytochrome C on apoptosis of AML cell induced by
      daunorudicine (DNR). The differentiation of AML cell was detected by Wright
      Giemsa staining and NBT test, the apoptosis of AML cell was assayed by flow
      cytometry and fluorescence microscopy. The results showed as follows: (1)
      different concentrations of cytochrome C could induce different effects on AML
      cells. Concentration of cytochrome C for differentiation was 10 microl/ml, for
      apoptosis was 20 microl/ml, and for necrosis was 40 microl/ml. (2) the apoptosis
      of AML cells decreased with the administration of cytochrome C in 10.0 microg/ml
      before treating AML cells with DNR (P < 0.01), but no change was shown with the
      administration of cytochrome C in 20.0 microg/ml (P > 0.05). (3) in reverse
      sequence, administrating of cytochrome C in 10 microl/ml and 20 microl/ml after
      treating AML cells with DNR, two different concentrations of cytochrome C could
      increase the apoptosis of AML cells (P < 0.01). It is suggested that cytochrome C
      may probably affect the apoptosis of AML cells induced by DNR.

PMID- 15854294
TI  - [Effect of bone marrow stromal cells on the apoptotic sensitivity of HL-60 and HL
      60/VCR cells].
AB  - This study was aimed to investigate the effects of human bone marrow
      fibroblastoid stromal cell line (HFCL) on chemosensitivity of acute myeloid
      leukemia sensitive HL-60 cell line and multidrug-resistant (MDR) HL-60/VCR cell
      line in vitro co-culture. Setting up co-culture system of HL-60 or HL-60/VCR
      cells in direct contact with HFCL cells, or with HFCL cells separated by
      transwell, and exposing HL-60 or HL-60/VCR cells to different concentrations of
      topotecon (TPT), morphologic evidence for apoptosis was determined by staining
      with Wright-Giemsa stain and acridine orange/ethidium bromide (AO/EB). Cell
      cycle, sub-G(1) and annexin V FITC staining were detected by flow cytometry. The
      expression of active caspase-3, Bcl-2 and Pgp was detected by Western blot. The
      results showed that HL-60 or HL-60/VCR cells treated by TPT revealed
      characteristic apoptotic morphological changes by Wright-Giemsa and AO/EB
      staining. The percentage of annexin V-positive cells and apoptotic cells
      decreased when they were cocultured with HFCL cells. The proportion of G(0)/G(1)
      HL-60 or HL-60/VCR cells treated by TPT increased and the sub-G(1) appeared
      significantly, but apoptotic and sub-G cells reduced after direct contact with
      HFCL cells. Meanwhile, although HL-60 or HL-60/VCR cells treated by TPT expressed
      activated caspase-3, and the expression of Bcl-2 decreased, the expression of
      activated caspase-3 decreased and Bcl-2 increased after direct contact with HFCL
      cells. In conclusion, HFCL stromal cells can prevent TPT-induced apoptosis in HL
      60 and HL-60/VCR cells via modulation of Bcl-2 and active caspase-3.

PMID- 15854295
TI  - [Effect of 2-methoxyestradiol on proliferation and apoptosis of myeloma cell
      lines].
AB  - The objective was to explore the in vitro effects of growth inhibition and
      apoptosis induction of 2-methoxyestradiol (2ME2), an estrogen derivative, on
      seven myeloma cell lines NCI-H929, HS-sultan, KM3, SKO-007, CZ-1, U266 and LP
      1and to observe its synergistic effects in combination with some other drugs,
      such as dexamethasone, As(2)O(3), thalidomide and zoledronic acid. Seven myeloma
      cell lines NCI-H929, HS-sultan, KM3, SKO-007, CZ-1, U266 and LP-1 were cultured
      at different concentrations with or without dexamethasone, As(2)O(3), thalidomide
      and zoledronic acid. Cell viability was assessed by trypan blue assay, plasma
      cell labeling index (PCLI) was detected by BrdU assay, terminal-deoxynucleotidyl
      transferase mediated dUTP nick end labeling (TUNEL) assay were used to determine
      apoptosis cells in situ. Synergistic effects of 2ME2 in combination with other
      drugs were judged by King's formula. The results showed that after treatment with
      1, 4, 8, 12, 16 micromol/L 2ME2 at 12, 24, 36 and 48 hours respectively, 2ME2
      caused a dose- and time-dependent inhibition of the cell viability. The
      concentration of 50% growth inhibition (IC(50)) was between (20.8 +/- 0.27) and
      (34.1 +/- 0.57) micromol/L. After treatment with 12 micromol/L 2ME2 within 24
      hours, 2ME2 led to a progressive decline in the fraction of S-phase cells by BrdU
      assay, plasma cell labeling index (PCLI) declined from (30.14 +/- 4.28)% to
      (14.71 +/- 6.27)% (P < 0.05). After treatment with 1, 4, 8, 12, 16 micromol/L
      2ME2 at 12, 24, 36 and 48 hours respectively, 2ME2 can induce a dose- and time
      dependent apoptosis of myeloma cell lines. The percentage of apoptosis was
      between 9% - 33% (P < 0.05). Q value of synergistic effects was between 1.13 to
      1.43. It is concluded that 2ME2 can inhibit proliferation and induce apoptosis of
      myeloma cell lines and has synergistic effects with dexamethasone, As(2)O(3),
      thalidomide and zoledronic acid.

PMID- 15854296
TI  - [Establishment of cytokine-independent human myelodysplastic cell line and its
      characteristics].
AB  - This study was aimed to establish a cytokine-independent human myelodysplastic
      cells line from bone marrow of a patient with MDS-CMML. This cell line was
      incubated in mixed culture of RPMI 1640 and DMEM with 15% bovine serum, but
      without cytokines; its biological characteristics were identified by morphology,
      surface marker profiles, cell proliferation, differentiation and apoptosis. The
      results showed that the established cell line could not depend on cytokines for
      long-term survival and growth, and could differentiate into colony-forming unit
      macrophage, colony-forming unit-megakaryocyte. In conclusion, a cytokine
      independent human myelodysplastic syndrome cell line, named MDS-JSN04 (MDS
      Nanjing Jiansu 04), was established. Its partial biological characteristics were
      identified and clarified.

PMID- 15854297
TI  - [Expression of platelet collagen receptor-glycoprotein VI fragment in E. coli and
      its biological activities].
AB  - This study was aimed to further investigate the function of platelet collagen
      receptor-glycoprotein VI and to screen its specific inhibitor. The extracellular
      domain of platelet glycoprotein VI (GPVI) in E. coli was expressed by recombinant
      technology, the extracellular domain cDNA of GPVI was amplified from pBluescript
      KS(-)-GPVI plasmid by PCR. Proved by sequencing, the expression vector pET-20b(+)
      GPVI was constructed, which was then transformed into E. coli (BL21(DE3)pLysS)
      and induced by IPTG. The recombinant GPVI was purified on Ni-NTA resin column and
      renatured in PBS containing GSH and GSSG. The anti-penta His McAb and anti-GPVI
      polyclonal antibody were used to identify the recombinant GPVI in Western
      blotting. Collagen binding test was conducted to investigate the biological
      activity of recombinant GPVI. The results showed that the recombinant GPVI was
      expressed in E. coli and successfully purified, which was confirmed to be similar
      to the native GPVI in Western blotting. The recombinant GPVI can bind the type I
      collagen in dose-dependent manner. In conclusion, the recombinant GPVI can be
      achieved in E. coli and restore its native characteristics after renaturation.

PMID- 15854298
TI  - [Slide platelet aggregation test used as a monitor for patient treated with anti
      pletelet drugs].
AB  - The aim was to verify the effectiveness of slide platelet aggregation test (SPAT)
      to monitor the inhibition effect of anti-platelet drugs. A group of eight healthy
      volunteers was examined for SPAT value and T(50) (time necessary for reaching 50%
      of total aggregation) induced by ADP, arachidonic acid (AA) and cationic propyl
      gallate (c-PG) respectively before and after administration of ASA in dose of 100
      mg/day for 3 days. The group of 41 inpatients at the Department of Cardiovascular
      Disease treated with anti-platelet drugs and the group of 327 healthy blood
      donors were also examined for SPAT. The SPAT value of healthy volunteer samples
      stored at room temperature were measured hourly for four hours. The results
      showed that: (1) no significant difference was detected between the T(50) before
      and after ASA administration in health volunteer group when ADP was used as
      inducer, but a significant difference was detected in this group when AA or c-PG
      was used as inducer. There was significant linear correlation between SPAT value
      and T(50) induced by c-PG in health volunteer group before and after
      administration of ASA (r = 0.998, P = 0.000); (2) there was no significant
      difference between the SPAT value of health volunteer group before administration
      of ASA and the SPAT value of health blood donors group (P = 0.853), but there was
      a significant difference between the SPAT values before and after administration
      of ASA in health volunteer group (P = 0.000). There was significant difference
      when the SPAT value of the inpatients treated with anti-platelet drugs was
      compared with that of healthy blood donor group and with that of health volunteer
      group before and after administration of ASA (P = 0.000). The cut-off value of
      SPAT in health blood donor group was 44.6 +/- 11.7 seconds, reference value was
      from 21.1 seconds to 68.0 seconds; (3) there was no significant difference
      between SPAT values when platelets samples stored at room temperature for 1, 2,
      3, 4 hours (P = 0.815). In conclusion, SPAT can rapidly monitor the inhibition
      effect of anti-platelet drugs and SPAT may have the similar clinic value with
      T(50) induced by c-PG.

PMID- 15854299
TI  - [Preparation of transfusable human universal red blood cell with recombinant
      alpha-galactosidase].
AB  - In order to meet the demand for safe transfusion in special conditions and to
      utilize the donated blood supply efficiently, technology has been developed to
      convert erythrocytes from type A, B, or AB to "universal donor" blood. Conversion
      of blood type B to O was performed by means of recombinant alpha-galactosidase
      digestion. The results showed that blood type B to O was converted successfully,
      1 transfusion unit of red cells of group B (100 ml totally) could converted to
      universal blood cells in the optimal conditions including pH 5.6, 26 degrees C, 2
      hours, obturation and sterilization. It is concluded that the universal red blood
      cells converted from group B to group O are conformed to demand of identification
      rules of biological products, no harmful effects of alpha-galactosidase on cell
      structure and function are observed. The converted red cells can stored in 4
      degrees C for 21 days.

PMID- 15854300
TI  - [Follow-up of 3 605 cord blood donors after 6 months of cord blood donation in
      Guangzhou cord blood bank].
AB  - To study the program of evaluating mothers and infants after 6 months of cord
      blood donation, from June 1998 to February 2004, all mothers after 6 months of
      cord blood donation were followed-up by phone calls or letters to report on the
      health condition. The results showed that when 3 195 mothers were visited by
      phone calls, 18 mothers declined to answer. 392 letter were send to those who
      could not be found by phone, 15 of whom wrote back. The average time to talk with
      each mother was approximately 12 minutes. Follow-up on the baby donors showed two
      cases with chromosome abnormality, one with hypothyroidism, one with neutropenia,
      one with albinism and 5 dead with unclear reasons. The cord blood components from
      all these abnormal donors found were discarded. In conclusion, the programs to
      evaluate mother and baby after 6 months of cord blood donation seems important in
      quality control of the components stored in cord blood bank.

PMID- 15854301
TI  - [Influence of repeated platelet donation on megakaryopoiesis in donors].
AB  - To explore influence of platelet donation on donor's megakaryocytopoiesis,
      platelet counts and plasma concentrations of thrombopoietin (TPO), interleukin-3
      (IL-3), IL-6 and nitric oxide (NO) were determined in 42 frequent platelet donors
      (undergoing plateletpheresis more than once a month for 24 months and their mean
      platelet yield of collection was 2.5 x 10(11)), in 62 limited platelet donors
      (undergoing plateletpheresis less than once a month for 24 months) after a
      donation-free period of > 5 weeks and in 40 whole blood donors who never
      undergoing plateletpheresis after a donation-free period of > 6 months. The
      results showed that the TPO levels was significantly lower in frequent platelet
      donors than in limited platelet donors (P < 0.01) and whole blood donors (P <
      0.01). There were no significant differences between three groups in platelet
      counts, IL-3, IL-6 and NO. These findings suggest that the number of
      megakarocytes significantly increased in frequent platelet donors.

PMID- 15854302
TI  - [Change of free hemoglobin content after mixing type B whole blood with different
      amounts of type O whole blood].
AB  - To investigate the changes of free hemoglobin (FHb) content after mixing type B
      whole blood with different amounts of type O whole blood at room temperature and
      at 37 degrees C, two lots of type B whole blood stored at 4 degrees C for 24
      hours were randomly taken as recipient blood, and were packed as 60 ml
      respectively. Type O blood was taken as donor blood. 60 ml type B whole bloods
      were mixed with different amounts of type O whole blood, i.e. with 9, 12, 15 and
      18 ml. The mixed blood was packed into 100 ml plastic blood bags and stored at 37
      degrees C or room temperature, shaken once every 15 minutes. Free hemoglobin
      content was determined for the harvested samples at 1, 2, 4, 8 and 12 hours after
      store. The results showed that there was no significant elevation of FHb within
      12 hours after mixing B whole blood with different amounts of type O whole blood.
      In another lot, there was obvious difference in FHb after 1 hour store along with
      the prolongation of store at either room temperature or 37 degrees C. In one lot,
      there was no difference of FHb (P > 0.05) during 1 - 8 hours of store at room
      temperature or 37 degrees C, but significant difference at 12 hours of store (P <
      0.001). In another lot, there was no difference of FHb (P > 0.05) within 1 hour
      of store at room temperature and at 37 degrees C, but significant difference
      during 2 approximately 8 hours of store (P < 0.001). It is concluded that the FHb
      would not change significantly within 12 hours after type B blood was mixed with
      1 200 ml of type O whole blood, but when the mixed blood was placed at room
      temperature or at 37 degrees C for 8 hours, the FHb content approaches, even
      exceeds 170.4 mg/L which was observed in the blood stored for 2 days. It suggests
      that freshly collected blood must be put into refrigerator of 2 approximately 4
      degrees C for storing as soon as possible, so as to decrease the catabolism of
      erythrocyte and the releasing of FHb and other metabolites which are deleterious
      to the recipients.

PMID- 15854303
TI  - [Clinical study on transplantation of G-CSF-mobilized allo-PBSC and allo-bone
      marrow for leukemia patients].
AB  - To study clinical outcome of G-CSF-mobilized allo-peripheral blood stem cell
      (PBSC) and allo-bone marrow (BM) transplantation for patients with leukemia,
      donors were injected G-CSF 8-10 microg/(kg.d) for 5 days, PBSC were collected on
      day 4-5 and G-CSF mobilized BM was extracted on day 7. Conditioning regimen
      consisting of fludarabine, busulfan and cyclophosphamide. The results showed that
      transplanted cells in all patients were engrafted, the median days of neutrophil
      exceeding 0.5 x 10(9)/L and platelet exceeding 20 x 10(9)/L were 10.2 days (range
      9 - 12 days) and 12.5 days (range 12 - 14 days), respectively. Patients were
      monitored up to 100 days, 4 of 12 patients (33.3%) developed II aGVHD, 10 of 12
      patients (83.3%) developed limited cGVHD. The median follow-up duration was 5
      months. Two patients died, the others were alive in disease-free situation. In
      conclusion, allogeneic transplantation of G-CSF mobilized PBSC plus BM was safe
      and effective treatment for patients with leukemia, the therapy provides rapid
      and sustained engraftment without increase in incidence of aGVHt and cGVHD.

PMID- 15854304
TI  - [Sensitivity and specificity analysis of the lineage related antibodies in acute
      leukemia immunophenotyping by flow cytometry].
AB  - To evaluate the sensitivity and specificity analysis of the lineage related
      antibodies in acute leukemia immunophenotyping by flow cytometry (FCM),
      immunophenotyping in 184 patients with acute leukemia was performed by FCM
      analysis. The results showed that in the lineage-related antibodies of acute
      myelocytic leukemia (AML), the sensitivity of CD13 and CD33 was higher (95.5% and
      91.2%, respectively), the specificity of them was deficient (72.5% and 62.2%,
      respectively); the sensitivity of MPO was low (69.1%), but the specificity was
      high (100%); the sensitivity and specificity of CD117 were high (88.2% and 100%,
      respectively); the sensitivity of CD14 and CD15 was low (18.4% and 27.2%,
      respectively); the specificity of CD14 with monocytes was high. As the lineage
      related antibodies of B-lineage ALL were concerned, CD19 showed high sensitivity
      and low specificity (100% vs 83.4%); the sensitivity and specificity of CD79a
      (96.4% vs 100%) and CD22 (100% vs 100%) were high; the sensitivity and
      specificity of CD10 (53.6% vs 82.5%) and CD20 (70.4% vs 87.5%) were low. In T
      lineage ALL, the specificity of CD3 was high (97.5%), but the sensitivity was
      below the mark (80.0%); the sensitivity of CD7 was high (100%), but the
      specificity was low (77.9%); while the sensitivity and specificity of CD5, CD2
      and CD1a were all deficient. In conclusion, the sensitivity and specificity
      analysis of the lineage-related antibodies in acute leukemia immunophenotyping
      are coincident with St Jude immunophenotyping project. It seems only that CD117
      is superior to MPO in defining AML, but the sensitivity and specificity analysis
      of CD22 and CD79 are similar in defining B-lineage ALL, therefore, anyone of them
      may be selected as your need.

PMID- 15854305
TI  - [Hematopoietic growth factor EPO has neuro-protective and neuro-trophic effects-
      review].
AB  - Erythropoietin (EPO) is an acidic glycoprotein that was first detected as a
      hematopoietic factor and its synthesis is triggered in response to cellular
      hypoxia-sensing. EPO binds to type I cytokine receptors, which associate with the
      non-receptor tyrosine kinase Jak2, and thereby activate Stat 5a/5b, Ras/MAPK, and
      PI3-K/Akt signaling pathways. The recent discovery shows that there is a specific
      EPO/EPO-receptor system in the central nervous system (CNS), independently of the
      haematopoietic system. Hypoxia and anemia can up-regulate EPO/EPOR expressions in
      the CNS. Further studies demonstrate that EPO has substantial neuro-protective
      effects and acts as a neurotrophic factor on central cholinergic neurons,
      influencing their differentiation and regeneration. EPO also exerts neuro
      protective activities in different models of brain damage in vivo and in vitro,
      such as hypoxia, cerebral ischaemia and sub-arachnoid haemorrhage. EPO may also
      be involved in synaptic plasticity via the inhibition or stimulation of various
      neurotransmitters. Therefore, human recombinant EPO that activate its receptors
      in the central nervous system might be utilized in the future clinical practice
      involving neuroprotection and brain repair.

PMID- 15854306
TI  - [Effects of rhG-CSF on T cell during peripheral blood stem/progenitor cell
      mobilization and its mechanisms--review].
AB  - Recombinant human granulocyte-colony-stimulating factor (rhG-CSF) can widely
      regulate human immunologic response. In the protocol of peripheral blood
      stem/progenitor cell mobilization, rhG-CSF can change the numbers and functions
      of T cells. Then the results can impact the incidence of graft-versus-host
      disease after allogeneic peripheral blood stem/progenitor cell transplantation.
      The regulation of rhG-CSF on T cell is an indirect action which is based on the
      direct action to monocytes and dendritic cells. The numerous IL-10 secreted by
      monocytes plays a key role in cytokines production, proliferative response and
      cytotoxicity of T cells. Endogenous IL-10 can induce high expression of SOCS3 and
      the SOCS3 is very important for regulating the signal transduction of the
      activities of T cells. In this review influences of rhG-CSF on T-cells in
      mobilization process and related mechanisms were elaborated with emphasis.

PMID- 15854307
TI  - [HOXB gene family and functions of hematopoietic stem/progenitor cells--review].
AB  - Recently, many researches indicated the important role played by homeobox (HOX)
      gene family in normal hematopoiesis. As a kind of transcription factors, HOX gene
      products regulate and control the expression of target genes by binding to
      special DNA sequences. HOXB, a member of HOX gene family, especially HOXB(4),
      interests people greatly. It has been found that its expression relates closely
      to the self-renewal of hematopoietic stem cells and effective proliferation of
      hematopoietic progenitor cells. This review presents some new research progress
      in this area.

PMID- 15854308
TI  - [Immunosuppressive therapy for aplastic anemia--review].
AB  - Immunosuppressive therapy (IST) is essential to treat aplastic anemia. The
      pharmacological mechanism, therapeutic effect of main drugs and their application
      method, reasonable dosage, synergistic action are briefly reviewed in this
      article. These reviewed drugs include ATG/ALG, CsA, ALG/ATG + CsA, IIST (ALG +
      CsA) + HGFs, McAb-T, HD-MP and HD-IVIG. The purpose of this review was to direct
      to clinical therapy for patients with aplastic anemia.

PMID- 15854309
TI  - [Continuous improvement of oral health in the 21st century: the approach of the
      WHO Global Oral Health Programme].

PMID- 15854310
TI  - [Reconstruction of accessory nerve defects with sternocleidomastoid muscle-great
      auricular nerve flap].
AB  - OBJECTIVE: To describe a new method of accessory nerve defect reconstruction with
      sternocleidomastoid muscle-great auricular flap. METHODS: Thirty-four cases
      receiving traditional radical neck dissection were divided into two groups:
      single neck dissection group (n = 19) and accessory nerve reconstruction group (n
      = 15). Surgical procedure of the reconstruction was described in detail.
      Postoperative shoulder functions were compared between the two groups. RESULTS:
      Accessory nerve reconstruction group experienced much better shoulder function
      recovery than that in single neck dissection group. CONCLUSIONS: Reconstruction
      of accessory nerve defects with sternocleidomastoid muscle-great auricular nerve
      flap is simple, effective and complication-free.

PMID- 15854311
TI  - [The usefulness of FDG-PET in patients with cervical lymphadenopathy].
AB  - OBJECTIVE: To assess the usefulness of 2-(fluorine-18) fluoro-2-deoxy-D-glucose
      (FDG) positron emission tomography (PET) in patients with cervical
      lymphadenopathy. METHODS: From March 1999 to October 2001, 27 patients with
      cervical lymphadenopathy were imaged with FDG-PET. Maximum and mean standard
      uptake value (SUVmax and SUVmean) of lymphadenopathy and SUV of normal cervical
      tissue (SUVneck) were measured. All 21 patients with malignant lymphadenopathy
      got pathologically confirmed. RESULTS: All 26 malignant lymph nodes in 21
      patients could be detected by FDG-PET. FDG uptake of these nodes was higher than
      that of cervical tissue (SUVmax, SUVmean and SUVneck were 4.62 +/- 2.31, 3.45 +/-
      2.74 and 0.55 +/- 0.08, respectively P < 0.001). Other 9 benign lymph nodes in 6
      patients couldn't be detected by FDG-PET. The accuracy of PET in 21 patients with
      malignant lymphadenopathy, was higher than those of routine examinations such as
      ultrasonography plus CT or MR (P < 0.001). CONCLUSIONS: FDG-PET allows effective
      diagnosis of patients with cervical lymphadenopathy and can contribute
      substantially to patient care.

PMID- 15854312
TI  - [Changes of bone height after vascularized fibular bone graft in mandibular
      reconstruction].
AB  - OBJECTIVE: To investigate the changes of vascularized fibular bone height after
      transplantation for mandibular reconstruction. METHODS: Thirty-two patients with
      mandibular defects were reconstructed with vascularized fibular bone.
      Postoperative follow-up pantomography was used to evaluate the changes of bone
      height. RESULTS: At different distance from the vessel pedicles, the changes of
      bone height showed no significant difference. The height of fibular bone
      decreased gradually with time and reduced by 6.64% at 1 year postoperatively.
      CONCLUSIONS: Multiple segmental osteotomies had no effect on blood flow and the
      different pieces of graft after modeling by osteotomy experienced the similar
      reconstruction. The volume of grafted fibular bone almost remained stable.

PMID- 15854313
TI  - [Radiographic evaluation of the quality of root canal filling in a dental
      teaching hospital].
AB  - OBJECTIVE: To evaluate the quality of root canal filling performed by dentists
      and advanced dental trainees (ADTs) and the current level of continuing education
      in a dental teaching hospital. METHODS: 2 043 cases, randomly completed by six
      dentists and eight ADTs over half a year, were divided into two groups. The
      quality of root canal filling was analyzed radiographically. RESULTS: The overall
      percentage of the adequate root filling was 49.6%. The percentages of the
      adequate teeth filling and root canals filling (59.9%; 63.9%) by dentists were
      significantly higher than those (40.1%; 47.4%) by ADTs. In addition, the
      frequency of the adequate root canals filling by ADTs in the last two months
      (57.8%) was significantly higher than that in the first two months (40.0%), and
      the adequate filling rate by ADTs during the last two months was close to that by
      dentists. CONCLUSIONS: The quality of root canal filling performed by dentists
      was adequate. There was a substantial improvement for ADTs in filling quality
      after six months training.

PMID- 15854314
TI  - [Immunization of rats with a targeted fusion anticaries DNA vaccine].
AB  - OBJECTIVE: To observe the expression of a targeted fusion anticaries DNA vaccine
      pGJA-P in situ. To compare the levels of specific antibodies and anticaries
      efficacy generated by pGJA-P and pGLUA-P, a fusion anticaries DNA vaccine.
      METHODS: pGJA-P was administrated intramuscularly or intranasally to rats, and
      the expression of recombinant protein was detected by immunohistochemistry
      technique. Wistar rats were fed a cariogenic diet and orally infected with S.
      mutans, then immunized with pGJA-P or pGLUA-P via the intramuscular or intranasal
      route. All rats received a booster immunization 2 weeks later. At the termination
      of the experiment, blood and saliva samples were collected for assay of
      antibodies by ELISA and jaws were obtained for caries evaluation by the Keyes
      method. RESULTS: Recombinant protein could be detected in muscle in
      intramuscularly immunized rats and in nasal mucosa in intranasally immunized
      rats. Rats immunized intramuscularly with pGJA-P had significantly higher serum
      IgG levels than others (P < 0.01). Rats immunized intranasally or intramuscularly
      with pGJA-P had significantly higher salivary IgA levels than others (P < 0.01).
      Keyes scores of pGJA-P groups were significantly lower than those of pGLUA-P
      groups and pCI groups (P < 0.01). CONCLUSIONS: pGJA-P could be correctly
      expressed in vivo. pGJA-P generated increased humoral immune response and
      anticaries efficacy compared with pGLUA-P.

PMID- 15854315
TI  - [Effect of irradiation on tooth hard tissue and its resistance to acid].
AB  - OBJECTIVE: To study the effect of irradiation on the susceptibility of radiation
      caries. METHODS: The structures of 56 teeth enamel and dentin of 63 roots were
      observed using SEM and the collagen fibre and the resistance to the acid were
      also investigated after irradiation of 30 Gy, 50 Gy and 70 Gy. RESULTS: The
      enamel structure changes were found after irradiation with different doses. The
      significant difference was found in the enamel changes between high or middle
      dose group and low dose group or control. The dentin morphology changed, some
      collagen fibre vanished and resistance to acid was reduced after irradiation with
      50 Gy and 70 Gy. CONCLUSIONS: The radiation reduced the resistance of teeth to
      the acid and increased the caries susceptibility.

PMID- 15854316
TI  - [The study of magnetic resonance sialography in diagnosing parotid diseases].
AB  - OBJECTIVE: To study the feasibility of diagnosing parotid disease with magnetic
      resonance sialography (MRS) and to select the optimal scanning sequence. METHODS:
      Twenty-three patients with parotid gland disease and 5 normal adults received
      sialography using magnetic resonance imaging technique and several sequences
      (including IR-FSE, FSE, SS-IR-FSE, SS-FSE) were used. After first scanning, the
      patients were scanned respectively 3 and 10 minutes after buccal application of
      vitamin C. And MR images of duct obtained. The images of parotid duct system were
      analysed and evaluated according to their displaying effects. Qualitative
      diagnosis was made based on MRI and those diagnosis were compared with
      pathological diagnosis after operation. RESULTS: Images of MR sialography clearly
      displayed the main duct and its branches of parotid gland and the pathological
      changes of duct, such as narrow, expanded, stoppage. Of the scanning sequences,
      IR-FSE was superior to others in manifesting the parotid gland duct (P < 0.05).
      The performance of images after being given vitamin C did not significantly
      improve the displaying effect. The accurate rate of qualitative diagnosis was
      95.6%. CONCLUSIONS: MR sialography can clearly display the parotid ducts and
      their pathological changes. The accurate rate of qualitative diagnosis of parotid
      disease was higher than that X-ray sialography.

PMID- 15854317
TI  - [Comparative study on the clinical appearances between acute and chronic anterior
      disc displacement without reduction].
AB  - OBJECTIVE: To compare the clinical appearances of TMD patients between acute and
      chronic anterior disc displacement without reduction. METHODS: Successive one
      hundred TMD patients with fully recorded documents diagnosed as anterior disc
      displacement without reduction (ADDw/oR) were included, 45 acute and 55 chronic
      ADDw/oR patients. Clinical appearances including signs and symptoms, maximal
      mouth opening, Fricton's craniomandibular index, condylar bone changes on
      radiograms, findings on arthrograms and MRI were compared. RESULTS: The main
      reason for asking treatment was joint pain in chronic, instead of limited mouth
      opening in acute patients. Clinical symptoms such as pain and limited mandibular
      movement showed improvement in chronic patients. Fricton's joint dysfunction
      index was higher in acute than in chronic patients, but muscle palpation index
      was higher in chronic than in acute patients, but Fricton's craniomandibular
      index was not significantly different between chronic and acute patients. The
      destructive bone changes of condyle on radiograms, the damage of stretched disc
      attachment on arthrograms and the morphological deformed disc on MRI were more
      frequently found in chronic than in acute patients. CONCLUSIONS: In acute
      patients there is a great likelihood that tissues are healthy and not
      morphologically changed, we suggest that early and efficacious intervention
      should be made to reposition the anterior displaced disc that may block the
      progress of pathological impairment to both the disc and the condyle of TMJ.

PMID- 15854318
TI  - [Clinicopathologic study of a family cherubism].
AB  - OBJECTIVE: To investigate the clinicopathologic features of familial cherubism
      and its differentiation from other giant cell lesions in jaws and the results of
      surgical treatments with a long-term follow-up. METHODS: Four cases of familial
      cherubism were reviewed and their clinical and radiographic features,
      histopathologic appearance, biochemical markers and surgical treatments analysed.
      RESULTS: Clinically, cherubism was characterized by bilateral painless swelling
      of jaws, mandibular deformity was common. Radiographs showed multilocular
      radiolucencies with sclerotic thickening border. Histopathologically, numerous
      randomly distributed multinucleated giant cells and vascular spaces within a
      fibrous connective tissue stroma with or without eosinophilic collagen
      perivascular cuffing were shown. The lesion regressed without treatment in 1
      cases. Curettage was performed in 3 cases with good results. CONCLUSIONS:
      Cherubism can be diagnosed according to its typical clinical and radiographical
      features with a positive family history. It might regress without treatment. But
      surgery intervention is suggested to improve physiological function and to solve
      the psychologic problem of the patients.

PMID- 15854319
TI  - [Clinical study on velopharyngeal function after maxillary advancement].
AB  - OBJECTIVE: To explore possible alterations in velopharyngeal function after
      maxillary advancement. METHODS: Ten patients (3 secondary deformity of cleft
      palate, 7 maxillary retrusion) had maxillary advancement surgery. Pre- and post
      operative examinations consisted of lateral cephalometric radiography,
      nasopharyngoscopy and speech recording. RESULTS: There was no significant changes
      on speech or velopharyngeal competence after maxillary advancement. Cleft palate
      patients appeared slight hypernasality and nasal emission. CONCLUSIONS: Good
      velopharyngeal function pre-operation is not affected after the surgery of
      maxillary advancement.

PMID- 15854320
TI  - [Clinical application of lateral lag screw in fixing intracapsular sagittal
      condylar fracture].
AB  - OBJECTIVE: To introduce the clinical application and curative effect of lateral
      lag screw technique in fixing condylar intracapsular sagittal fractures. METHODS:
      Thirteen condyles with intracapsular sagittal fracture of 11 cases were fixed
      using lateral lag screw technique. Curative effects were observed by clinical and
      radiological follow-up for 6 approximately 30 months (mean 12 months)
      postoperatively. RESULTS: The favorable results were obtained in all cases. All
      patients were satisfied with the clinical results. slight malocclusion existed in
      2 cases. Radiological abnormalities were seen in 3 cases by CT scanning, but
      without any obvious function disturbances. CONCLUSIONS: Lateral lag screw
      technique is a simple and effective treatment in fixing intracapsular sagittal
      condylar fractures.

PMID- 15854321
TI  - [Preliminary study of tooth measured by a noncontact 3D image survey system].
AB  - OBJECTIVE: To perform the quantitative study of tooth occlusal surface wear by a
      noncontact 3D image survey system. METHODS: Thirty-two old people's complete
      dental casts in five years which had normal occlusion were studied. The same way
      was used to determine the individual reference surface, and the range of the
      maxillary first molar occlusal surface was delimited by the unite regulation.
      Then the quantity of wear in five years and wear rate of maxillary first molar
      occlusal surface were measured by the noncontact 3D image survey system. RESULTS:
      Wear of maxillary first molar occlusal surfaces was as follows: the mean height
      loss was 0.293 mm in five years and the mean wear rate was 0.059 mm/year; the
      mean volume loss was 97.881 mm(3) in five years and the mean wear rate was 19.576
      mm(3)/year. CONCLUSIONS: Under the necessary conditions, the noncontact 3D image
      survey system is an effective method to measure the wear of dental occlusal
      surface, but some set-up conditions need to be improved further.

PMID- 15854322
TI  - [Production of interleukin-11 in human gingival fibroblasts stimulated with IL
      1alpha and tumor necrosis factor-alpha].
AB  - OBJECTIVE: To investigate what role IL-11 plays in periodontal disease and to
      determine the level of IL-11 in HGFs stimulated with IL-1alpha and TNF-alpha.
      METHODS: HGFs were stimulated with IL-1alpha and TNF-alpha alone or in
      combination. The production of IL-11 was measured using enzyme-linked
      immunosorbent assay (ELISA). IL-11 and Glyceraldehyde 3-Phosphate Dehydrogenase
      (GAPDH) messenger RNA (mRNA) levels in HGFs were determined by real-time reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: IL-1alpha
      significantly increased the levels of IL-11 in HGFs. TNF-alpha also significantly
      augmented IL-11 production in HGFs, and synergistically stimulated HGFs to
      produce IL-11 when combined with IL-1alpha. Indomethacin, an inhibitor of
      prostaglandin synthesis, significantly reduced IL-11 production by HGFs
      stimulated with IL-1alpha and TNF-alpha individually or in combination. IL-1alpha
      alone or combined with TNF-alpha enhanced the ratio of IL-11/GAPDH mRNA
      expression in HGFs, and the augmentation was abolished by indomethacin after co
      incubation for 24 hs. CONCLUSIONS: Production of IL-11 in HGFs stimulated with IL
      1alpha and TNF-alpha was transcriptionally upregulated by the endogenous
      prostaglandin synthesis. Inhibition of prostaglandin might suppress the
      osteoclastogenesis by IL-11 in inflammatory periodontal diseases.

PMID- 15854323
TI  - [Study on the mechanism of discoloration and the efficacy of bleaching in non
      infected traumatically discolored teeth].
AB  - OBJECTIVE: To investigate the mechanism of discoloration and the efficacy of
      bleaching in non-infected traumatically discolored teeth. METHODS: In vitro model
      of discolored teeth: sample of fresh erythrocytes was placed in the pulp cavity
      of 20 extracted teeth and centrifuged for 3 consecutive days. These discolored
      teeth were divided equally and randomly into two groups: group A (control group);
      group B (bleaching group), bleached with 10% carbamide peroxide gel for 4 weeks.
      And then all teeth were prepared for histological examination and subjected to a
      series of histochemical tests to analyze some of the biochemical changes
      following haemorrhage into the pulp chamber and post-bleaching. RESULTS:
      Haemoglobin and haematin were detected in the dentinal tubules of discolored
      teeth from group A and no evidence of ferric or haemosiderin. Specimens from
      group B demonstrated a negative response to histochemical tests. CONCLUSIONS: In
      the absence of bacterial invasive, haemoglobin and haematin could cause
      discoloration of non-infected traumatized teeth. Peroxide bleaching agent can
      effectively remove haemoglobin and haematin.

PMID- 15854324
TI  - [Microtensile bond strengths of three dentin adhesive systems].
AB  - OBJECTIVE: To evaluate in vitro the microtensile bond strengths of three dentin
      adhesive systems and their respective fracture modes. METHODS: A total of 15
      intact young human premolars extracted for orthodontic reasons were used. The
      enamel of occlusal surfaces of these premolar teeth was removed and superficial
      dentine was exposed, finished with wet 600-grit silicon carbide paper. And then
      these teeth were randomly divided into three groups. A block of composite resin
      was bonded respectively with three dentin adhesive systems: All-bond 2 (Group
      AB(2)), Fluoro-Bond (Group FB) and Xeno III (Group Xeno) according to
      manufacturers' instructions. The bonded teeth were kept in distilled water for 24
      h at 37 degrees C. The roots were removed from the remaining crown approximately
      1 - 2 mm below the cemento-enamel junction with a slow-speed diamond saw. The
      teeth were sectioned to obtain bar-shaped specimens, whose bonded surface areas
      were about 0.8 mm(2). The specimens were stressed at a crosshead speed of 1
      mm/min until rupture of the bond. SEM was used to observe the fracture modes. The
      mean bond strengths were compared using one-way ANOVA and LSD tests. The
      frequency of fracture modes was compared using Krukal-Wallis and Mann-Whitney U
      test. RESULTS: Mean microtensile bond strengths were (29.56 +/- 5.47) MPa for
      Group AB(2), (15.81 +/- 7.67) MPa for Group Xeno, and (14.61 +/- 4.50) MPa for
      Group FB. The bond strength of Group AB(2) was greater than those of the other
      two groups (P < 0.01). The bond strengths of Group Xeno and Group FB were not
      significantly different. SEM examination indicated that the adhesive failure was
      the most mode of fracture. CONCLUSIONS: The microtensil bond strengths of three
      dentin adhesive systems to normal human dentine were different and the total
      etching adhesive All-Bond 2 exhibited the greatest bond strength. It was
      recommended that dentin adhesive agent should be used according to clinical
      situation.

PMID- 15854325
TI  - [Effects of TCP/HA-coating titanium on the adhesion behavior of human gingival
      fibroblasts].
AB  - OBJECTIVE: To investigate effects of hydroxyapatite (HA) and porous tricalcium
      phosphate/hydroxyapatite (TCP/HA)-coating titanium on the adhesion behavior of
      human gingival fibroblasts (HGFs). METHODS: Coatings of HA and duplex phases
      TCP/HA on titanium (Ti) were formed by ion beam assisted deposition (IBAD)
      method. Attachment, spreading, extracellular matrix (ECM) production, and focal
      adhesion plaque formation of HGFs were investigated on commercially pure (CP)
      titanium, HA-coated CP titanium and porous TCP/HA-coated CP titanium. After
      incubation of HGFs on these substrates, the number of attached cell, the area of
      cell spreading, immunostained ECM including fibronectin (FN) and type I collage,
      and vinculin (presenting the formation of focal adhesion plaque) were quantified
      by morphometric analysis using immunofluorescence microscope. RESULTS: TCP/HA and
      HA coatings exhibited that the attached cell number and cell spreading area were
      greater than those of CP titanium (P < 0.05), and the formation of focal adhesion
      plaque was earlier than that of uncoated substrate (P < 0.05). The number of
      attached cell and the formation of type I collagen on TCP/HA were more than those
      on Ti and HA. After 24-hour incubation on TCP/HA surface, the number of attached
      cell was 198.1 +/- 27.7 and the fluorescent intensity of type I collagen was
      154.10 +/- 31.56. While under the same condition, the corresponding numbers for
      the CP titanium were 125.1 +/- 29.9 and 132.63 +/- 35.26. The differences between
      the two groups were significant (P < 0.05). CONCLUSIONS: In this study, the
      porous TCP/HA coating significantly facilitated the adherence of human gingival
      fibroblasts to Ti surface and could improve the biocompatibility of titanium.

PMID- 15854326
TI  - [Clinical application of miniscrew implant for maximum anchorage cases].
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficiency of the self
      drilling miniscrew implant for maximum anchorage cases. METHODS: The study
      comprised 5 patients whose ages ranged from 14 to 31 years. All patients
      presented with. Class II skeletal pattern, maxillary protrusion or bimaxillary
      protrusion. Maximum molar anchorage and first premolar extraction were required.
      In the stage of anterior teeth retraction, self-drilling miniscrew implants were
      inserted into the buccal alveolar bone between maxillary second premolar and
      first molar. Sliding mechanics with 150 - 200 g force was used to retract
      anterior teeth. The cephalometric films before and after retraction were
      measured. RESULTS: Dental protrusion and facial profile were improved
      significantly in all patients. The edge of upper incisors was retracted 6.4 mm
      and anchor molar moved anteriorly 0.3 mm averagely. All miniscrew implants
      remained stable during treatment and peri-implant soft tissue remained healthy.
      CONCLUSIONS: Self-drilling minisrcew implant could be used as an efficient method
      for anchorage control and an alternative choice of extra-oral forces.

PMID- 15854327
TI  - [Application of straight wire appliance for pre- and post-surgical orthodontics].
AB  - OBJECTIVE: To analyze the surgical patients treated with straight wire appliance
      for guidelines of clinical using of the appliance. METHODS: Totally 51 patients
      from Joint Clinic of Orthodontic Surgery, Peking University School of Stomatology
      with dentofacial deformities treated with straight wire appliance were analyzed.
      The patients were aged from 15 years to 34 years 5 months, average 18 years 9
      months. Among whom, 16 are males, while the other 35 are females. RESULTS:
      Eighteen patients were treated with extraction of teeth, while other 33 cases
      were nonextraction case. The duration of average presurgical orthodontic
      treatment was 13.3 months, and 10.4 months was for postsurgical orthodontic
      treatment, totally active treatment time was 25.5 months. CONCLUSIONS: Straight
      wire appliance would benefit a lot for three dimensional control of teeth when
      doing pre- and post-surgical orthodontic treatment. Good results could be
      achieved without wire bending.

PMID- 15854328
TI  - [Applied anatomy of adult mandibular ramus].
AB  - OBJECTIVE: To study applied anatomy of adult mandibular ramus and condyle.
      METHODS: Observation and measurement were made on 16 adult mandibular rami and
      condyles. RESULTS: Thickness became gradually greater within 15 mm from the back
      edge of ramus. Some adult mandibular rami had no spongy bone at the level of 10
      mm above mandibular foramen. CONCLUSIONS: These date are very important for
      application of lag screw osteosynthesis in condylar fracture.

PMID- 15854329
TI  - [To be an excellent dentist in clinic].

PMID- 15854330
TI  - [A review guideline and strategy for the candidates of national certificated
      dentist qualification test].

PMID- 15854331
TI  - [Development and advancement in periodontal tissue engineering].

PMID- 15854332
TI  - [The evolution on alveolar ridge augmentation by distraction osteogenesis].

PMID- 15854333
TI  - [The advances of thalidomide in oral mucosal uses].

PMID- 15854334
TI  - [Surgical treatment of chronic pulmonary thromboembolism].
AB  - OBJECTIVE: To evaluate the perioperative management and safety of pulmonary
      thromboendarterectomy for chronic pulmonary thromboembolism. METHODS: From March
      1999 to March 2004, 12 patients with chronic pulmonary thromboembolism received
      thromboendarterectomy. The operation was performed under cardio-pulmonary bypass
      with low flow or circulative arrest and deep hypothermia. The clinical data of
      the 12 cases were reviewed retrospectively. RESULTS: Pulmonary pressure
      immediately decreased 20 to 40 mm Hg (1 mm Hg = 0.133 kPa) after operation in 6
      cases. Various degrees of postoperative pulmonary edema happened in 8 cases. One
      patient died at the 19th day after operation due to severe lung infection and
      pulmonary re-embolism. Eleven patients were followed-up for 2 months to 5 years,
      the clinical symptom and routine daily activity were improved after surgery.
      CONCLUSION: Pulmonary thromboendarterectomy is an effective treatment for chronic
      pulmonary thromboembolism. It is very important to management of postoperative
      reperfusion injury and pulmonary edema. A key point to enhance the safety of
      surgical treatment for chronic pulmonary thromboembolism is preoperative correct
      evaluation and indication selection.

PMID- 15854335
TI  - [Diagnosis and surgical treatment of metachronous second primary lung cancer].
AB  - OBJECTIVE: To review the experience of the diagnosis, surgical treatment and
      prognosis of metachronous second primary lung cancers. METHODS: Between January
      1983 and April 2004, 32 patients with metachronous second primary lung cancers
      were operated in our department. Clinical data of all these patients were
      reviewed retrospectively. RESULTS: The initial procedures for their first primary
      lung cancers were lobectomy or pneumonectomy. Lobectomy or completion
      pneumonectomy for the second primary lung cancers were performed in 17 cases,
      limited pulmonary resection was done in 14 cases and exploration was in 1 case.
      The postoperative morbidity and mortality were 12% (4/32) and 3% (1/32),
      respectively. The 1-, 3-, and 5-year survival rate after second operation were
      66% (19/29), 32% (9/28) and 19% (4/21), respectively. CONCLUSIONS: The incidence
      of metachronous second primary lung cancers has been increasing gradually during
      recent years. The closely follow-up for patients undergoing resection for their
      first primary lung cancers is most important factor for improvement of the
      diagnosis of metachronous second primary lung cancers. Limited resection and
      incomplete lymph node dissection might be the factors contributing to the poor
      prognosis.

PMID- 15854336
TI  - [Hand-assisted video-thoracoscopy for resection of esophageal cancer].
AB  - OBJECTIVE: To explore the feasibility and advantages of hand-assisted video
      thoracoscopy for resection of esophageal cancer. METHODS: Forty-five patients
      with esophageal cancer received hand-assisted video-thoracoscopic esophagectomy
      (group I). 45 patients underwent esophagectomy through routine open thoracotomy
      during the same period as control (group II). The data of lymph node resection,
      operating time and blood loss were compared. RESULTS: There were no operative
      mortality in 2 groups. In group I, the number of dissected paraesophageal lymph
      nodes, cardiac lymph nodes and left gastric nodes were (3.6 +/- 1.0), (1.3 +/-
      1.1) and (4.3 +/- 1.4), respectively. While for group II the dissected lymph
      nodes were (3.3 +/- 1.5), (1.6 +/- 1.1) and (4.7 +/- 2.1), respectively. There
      was no significant difference between two groups (P > 0.05). However, the number
      of dissected mediastinal nodes was (6.6 +/- 3.7) for group I and (3.8 +/- 2.5)
      for group II (chi(2) = 2.95, P < 0.05). The mean operating time was (29 +/- 5)
      minutes for group I and (60 +/- 6) minutes for group II. The mean blood loss was
      (93 +/- 19) ml for group I and (145 +/- 35) ml for group II. The mean chest tube
      drainage was (201 +/- 45) ml for group I and (295 +/- 57) ml for group II in the
      first postoperative day. The difference in above parameters between 2 groups was
      significant (chi(2) = 18.69, 6.13, 6.08, P < 0.001). CONCLUSIONS: It is suggested
      that hand-assisted video-thoracoscopic esophagectomy is a safer, minimal invasive
      procedure in the resection of esophagus carcinoma.

PMID- 15854337
TI  - [The clinical significance of vascular endothelial growth factor and
      intercellular adhesion molecule-1 expression in non-small cell lung cancer].
AB  - OBJECTIVE: To investigate the expression of vascular endothelial growth factor
      (VEGF) and intercellular adhesion molecule-1 (ICAM-1), and their relationship to
      behaviors of the non-small-cell lung cancer. METHODS: The study included 86
      patients with non-small-cell lung cancer. A rapid immunohistochemical method
      (streptoavidin-peroxidase, SP) was used to detect VEGF and ICAM-1 expression. All
      patients were treated surgically and without preoperative radio- or chemotherapy.
      RESULTS: The positive expression of VEGF was significantly correlated with the
      lymph node metastasis, TNM stage, prognosis and hematogenous tumor metastasis
      positively, but ICAM-1 was negatively. For patients with positive expression of
      VEGF and negative expression of ICAM-1, the 5-year survival rate was the lowest
      in all patients. CONCLUSIONS: The expression of VEGF and ICAM-1 correlates with
      the malignant behavior of non-small-cell lung cancer. Examination of VEGF and
      ICAM-1 in non-small-cell lung cancer may help to evaluate its intensity of lymph
      node metastasis, TNM stage and prognosis. VEGF and ICAM-1 may play an important
      role in the development and metastasis of non-small-cell lung cancer.

PMID- 15854339
TI  - [Surgical treatment of active infective endocarditis].
AB  - OBJECTIVE: To summarize the recent experience of surgical management of the
      active infective endocarditis (IE) disease in Fuwai Hospital. METHODS: From
      October 1, 1996 to December 31, 2003, 54 patients with active IE underwent heart
      operation in Fuwai Hospital. There were 41 males, 13 females, with an average age
      of 35 years old and an average weight 58 kg. Of the cases, 23 had congenital
      anomalies of the heart, and 1 had rheumatic valvulitis. Streptococci were found
      in 20 patients, staphylococci in 3, enterococci in 1, enterococcus in 2 and G(+)
      cocci in 1. Pre-operative cardiac classification (NYHA): class I was in 6 cases,
      class II in 12 cases, class III in 7 cases and class IV in 29 cases. Systemic
      embolization occurred in 23 cases and pulmonary infarction in 2 cases. Emergent
      operations were performed in 27 cases because of heart failure (8 cases),
      embolism (4 cases), aggressive infection (3 cases), heart failure plus embolism
      (2 cases), heart failure with aggressive infection (4 cases), aggressive
      infection with embolism (2 cases) and all the three factors (4 cases). The
      operations included aortic valve replacement (25 cases), aortic and mitral valves
      replacement (15 cases), mitral valve replacement (6 cases), mitral valve repair
      (3 cases), pulmonic valve replacement (1 case) and intracardiac shunt repair (4
      cases). RESULTS: The operative mortality was 17% (5 operative death and 4 lost in
      following-up after being discharged). All of operative deaths were due to
      infection. Fourteen patients had operative complications. The morbidity included
      peri-prosthetic leakage (8 cases), prosthetic IE (5 cases), residual intracardiac
      shunt (2 cases), complete heart block (2 cases), myocardial infarction,
      ventricular fibrillation, pulmonary trunk stenosis, and mitral regurgitation (1
      case in each). Post-operative cardiac classification (NYHA): class I was in 41
      cases, class II in 3 cases, class III in 1 case. Two patients were re-operated
      because of peri-prosthetic leakage, and then they were cured. Re-operation was
      also performed in other 3 patients. Unrelated late sudden death occurred in 1
      patient and hemiplegia caused by anticoagulant intracranial hemorrhage in another
      patient. CONCLUSION: Acceptable results can be achieved with active surgical
      intervention in active patients with IE.

PMID- 15854340
TI  - [Effects of taurine on early changes of excitatory amino acids in rabbit brain
      due to deep hypothermic circulatory arrest].
AB  - OBJECTIVE: To study the effects of taurine (Tau) on early changes of excitatory
      amino acids (EAA) in hippocampus rabbit brain due to deep hypothermic circulatory
      arrest (DHCA). METHODS: Sixteen New Zealand rabbits were randomly allocated into
      2 groups: Tau 150 mg/kg group (group I, n = 8), control group (group II, n = 8).
      Cardiac pulmonary bypass (CPB) was set up after cerebral microdialysis model was
      established. High performance liquid chromatography was employed to monitor the
      continuous changes of glutamic acid (Glu), aspartic acid (Asp), Tau and glycine
      (Gly) in the hippocampus CA1 region at anaesthesia periods, CPB stage, pre 30
      minutes in DHCA, post 30 minutes in DHCA, pre 30 minutes in rewarming, post 30
      minutes in rewarming. RESULTS: The increase of Glu in group II was (5.1 +/- 1.5)
      and (4.1 +/- 1.4) times higher than that at anaesthesia periods (t = 3.74, 5.45,
      P < 0.01), and the increase of Glu in group I was (2.1 +/- 1.5) and (1.1 +/- 0.4)
      times than that at anaesthesia periods at pre 30 minutes and post 30 minutes
      rewarming stage respectively. Rising of Gly in group II was 6.7 (3.6, 13.6) times
      than that at anaesthesia periods (T = 75.00, P < 0.05), the rising of Gly in
      group I was 4.2 (3.8, 11.5) times at post 30 minutes in DHCA. Rising of Tau in
      group I was 6.9 (3.0, 14.2) and 10.6 (2.8, 22.5) times than that at anaesthesia
      periods (T = 75.00, P < 0.05 and T = 90.00, P < 0.05) and rising of Tau in group
      II was 4.0 (3.0, 5.7) and 3.2 (1.2, 7.6) times than that at anaesthesia periods
      at post 30 minutes in DHCA and pre 30 minutes rewarming stage respectively. Asp
      was no evident change at every periods. CONCLUSION: DHCA might increase the
      excitatory amino acids in the early phases of circulatory restoration. Exterior
      Tau 150 mg/kg could inhibit release of EAA.

PMID- 15854341
TI  - [Construction of a tissue-engineered valve with decellular porcine aortic valve
      scaffold in the abdominal aorta of canine].
AB  - OBJECTIVE: To explore an experimental method for construction of tissue
      engineered heart valve (TEHV) in canine abdominal aorta. METHODS: The decellular
      porcine aortic valve (PAV) leaflets seeded with canine vessel interstitial cells
      and endothelial cells (ECs) were implanted into 6 canine abdominal aortas. Valve
      specimens were obtained respectively at the end of 4, 6, 8 and 10 weeks after
      implantation were studied for morphology, histology and immunohistochemistry.
      RESULTS: (1) After 4 weeks implantation, multiple layers of cells grew into
      peripheral portion of valve scaffold, while new extracellular matrix appeared,
      and original scaffold tissue was partially absorbed. (2) At the end of 10th week
      after implantation, the decellular PAV scaffold disappeared completely and was
      substituted by recipient cells and new extracellular matrix. The interstitial
      cells in matrix was mainly consisted of fibroblasts and myofibroblast. The matrix
      was mainly composed by type I, III collagen, some elastic fibers with neutral and
      acid mucopolysaccharide. (3) Surface of valve leaflets were covered with
      endothelial cells. CONCLUSIONS: (1) TEHV is primarily constructed with
      recellularized PAV after implantation into canine abdominal aorta for 10 weeks.
      (2) Heterotopic implantation into the abdominal aorta is an alternative
      experimental procedure to study the TEHV.

PMID- 15854346
TI  - [Clinical study of CT virtual endoscopy in staging diagnosis of bladder tumors].
AB  - OBJECTIVE: To evaluate CT virtual endoscopy (CTVE) based on spiral CT in the
      staging diagnosis of bladder neoplasms and its clinical application. METHODS:
      Forty patients with bladder neoplasms and 10 normal patients underwent volume
      scanning using spiral CT. All images with thin collimation and overlapping
      reconstruction were transferred to computer workstation to obtain the images of
      CTVE. The results of all CTVE findings were compared with those of conventional
      CT, cystoscopy, operation and pathological data. RESULTS: CTVE showed the normal
      anatomical structure of bladder as actual cystoscopy. The size, configuration,
      location and extension of bladder neoplasms was detected by CTVE scans agreed
      with that of actual cystoscopy. CTVE revealed the structure of trigone of urinary
      bladder that were not available in actual cystoscopy, and they were confirmed
      operatively and compared with the pathological results according to the TNM
      classification of malignant neoplasms. The sensitivity of CTVE for bladder tumors
      and accuracy in preoperative neoplasms staging was 98% (39/40) and 85% (33/39),
      respectively. The sensitivity of mass detection of diameter > or = 0.5 cm was
      100%. The results were studied in a blind way. CONCLUSIONS: CTVE is a
      noninvasive, safe and reliable procedure in the staging diagnosis of bladder
      neoplasms. CTVE can well show bladder neck anatomy and serve as an important
      complementary method to conventional cystoscopy. The limitation of CTVE is that
      it can not observe change of mucosal appearances and perform biopsy.

PMID- 15854347
TI  - [Expression of SSX2 gene in human urologic neoplasms].
AB  - OBJECTIVE: To investigate the expression of SSX(2)gene in human renal cell
      carcinoma and urinary transitional cell carcinoma. METHODS: Reverse-transcription
      polymerase chain reaction (RT-PCR) was used for detecting SSX(2) gene in the
      specimens from renal cell carcinoma (n = 26), urinary transitional cell carcinoma
      (n = 27) and in 15 specimens taken from the tumor surrounding tissues. RESULTS:
      Positive expression of SSX(2) gene at mRNA was detected in 69% renal cell
      carcinomas (18/26), in 81% urinary transitional cell carcinomas (22/27). The mRNA
      of SSX(2) was not detected in the 15 specimens from tumor surrounding tissues.
      CONCLUSION: The SSX(2) gene is highly expressed in human renal cell carcinoma and
      urinary transitional cell carcinoma.

PMID- 15854349
TI  - [Correlation of benign prostatic hyperplasia with hyperlipemia].
AB  - OBJECTIVE: To investigate relationship between benign prostatic hyperplasia (BPH)
      and hyperlipemia, and to clear out possible factors related to BPH etiology.
      METHODS: A total of 462 cases of BPH diagnosed by pathological examination were
      studied retrospectively. RESULTS: Of 462 cases, BPH with hyperlipemia was noted
      in 232 cases (50.22%). In comparison with the data of simple BPH, both prostate
      volume (P = 0.029) and residual urine (P = 0.03) were significantly increased in
      the BPH patients with hyperlipemia. Statistical analysis regarding the effects of
      different components of serum lipid on BPH clinical factors showed that the level
      of high density lipoprotein was significantly associated with both the
      enlargement of prostate volume (P < 0.05) and increasing of serum PSA (P < 0.05)
      Further study indicated that hypertension was demonstrated in 39.2% patients of
      BPH with hyperlipemia. Hyperlipemia accompanied with hypertension in BPH patients
      was significantly related to increased IPSS (P = 0.004). CONCLUSION: The
      situation of BPH with hyperlipemia is frequently noted in clinics, and the
      decreased level of high-density lipoprotein is significantly associated with the
      enlargement of prostate volume. Co-existence of hypertension with hyperlipemia in
      BPH patients greatly worsens the lower urinary tract symptoms (LUTS) of BPH.
      Hyperlipemia may be one of the risk factors in the processes of BPH growth and
      progression.

PMID- 15854348
TI  - [The effect of cell killing and apoptosis by human herpes simplex virus-
      thymidine kinase/ganciclovir system combined with allitride in BIU87 cells].
AB  - OBJECTIVE: To study the killing effect of human herpes simplex virus-thymidine
      kinase/ganciclovir (HSV-TK/GCV) system combined with allitride and the possible
      apoptosis mechanism in BIU87 cells. METHODS: The cytotoxicity after combination
      were estimated by theamine blue tetrazolium bromide (MTT). The morphological
      changes were observed with inverted microscope and in-situ cell apoptosis
      detection kit. Changes of apoptosis rate and cell cycle were assessed by flow
      cytometry. B-cell lymphoma-2 (bcl-2), bax, caspase-3 (cysteine aspartate specific
      proteinase) mRNA changes were detected by reverse transcriptase polymerase chain
      reaction, and caspase-3 activity was estimated with colorimetry. RESULTS: For
      combination group, the cell killing rate was raised to 72.50% to compare with
      35.00% of GCV and 37.00% of allitride separately and there was a synergistic
      effect between these two drugs. The cell apoptosis was induced in all three
      groups and for the combination group the time of S-phase and G(2)-phase arrest
      were earlier than other two groups. Both drugs could inhibit the expression of
      bcl-2 and promote the expression and activity of caspase-3. CONCLUSIONS: The
      combination of HSV-TK/GCV system with allitride can inhibit the proliferation of
      BIU87 cells congenerously through apoptosis, which may be correlated with S- and
      G(2)-phase arrest, down-regulation of bcl-2 and increased caspase-3 expression
      and its activity.

PMID- 15854350
TI  - [The expression of hypoxia inducible factor-1,2 alpha in sporadic clear cell
      renal cell carcinoma and their relationships to the mutations of von Hippel
      Lindau gene].
AB  - OBJECTIVE: To evaluate the expression of hypoxia inducible factor (HIF)-1alpha,
      2alpha in sporadic clear cell renal cell carcinoma and their relationships to the
      mutations of von Hippel-Lindau (VHL) gene. METHODS: Mutations of VHL gene,
      expression of HIF-1alpha and 2alpha were detected by polymerase chain reaction
      (PCR), direct DNA sequencing and immunohistochemistry in 77 cases of Chinese
      sporadic clear cell renal cell carcinoma (CCRCC). The stage was pT(1)N(0)M(0)in
      55 patients (71%), pT(2)N(0)M(0) in 7 patients (9%), pT(3)N(0)M(0) in 14 patients
      (18%), and pT(4)N(0)M(0) in 1 patient (1%). The classification according to the
      tumor nuclear grading system showed 15 carcinomas (19%) of tumor nuclear grade 1,
      56 (73%) of tumor nuclear grade 2 and 6 (8%) of tumor nuclear grade 3. RESULTS:
      None of the VHL gene mutations were found in all the normal tissue specimens. VHL
      gene mutations were detected in 40 (52%) cases of CCRCC. The positive rate of HIF
      2alpha (81%) was higher than that of HIF-1alpha (66%) (chi(2) = 23.310, P <
      0.01); The positive rate of HIF-1alpha and HIF-2alpha in the cases of mutations
      (98% and 93% respectively) was higher than that of them in non-mutations (32% and
      68% respectively) (chi(2) = 36.386, 7.617, P < 0.01); The correlation between HIF
      1alpha and VHL gene mutations was closer than that between HIF-2alpha and VHL
      gene mutations (partial correlation coefficiency was 4.481 and 2.027
      respectively, P < 0.01). The expression of HIF-1alpha and 2alpha in different
      pathological grade and stage of CCRCC showed no significant difference (P >
      0.05). CONCLUSIONS: Our study suggests that VHL gene mutations are frequent in
      sporadic CCRCC, and the high expression of HIF-1alpha and 2alpha are found in the
      group of VHL mutations. However, we have not found significant correlation
      between the expression of HIF-1alpha and 2alpha and pathological grade and stage
      of CCRCC in our study.

PMID- 15854351
TI  - [Short-term neoadjuvant hormone therapy enhanced expression of clusterin in
      prostate cancer].
AB  - OBJECTIVE: To define changes in clusterin expression following short-term
      neoadjuvant hormone therapy (NHT) and its biological significance in prostate
      cancer tissues. METHODS: Twenty-six archival radical prostatectomy (RP) specimens
      without receiving NHT, 19 needle biopsies and corresponding 19 RP specimens
      following 3-month NHT, were subjected to immunohistochemical clusterin staining.
      RESULTS: Staining for clusterin was mainly found in cytoplasm and part of
      extracellular matrix. Clusterin expression was significantly greater in RP
      specimens with preoperative NHT (t = 2.91, P < 0.01); Needle biopsies obtained
      before NHT consistently demonstrated lower staining intensity (1.42 +/- 0.51)
      than corresponding RP specimens (2.16 +/- 0.60) following 3-month NHT (t = 7.10,
      P < 0.01). CONCLUSIONS: Upregulation of clusterin in part accounts for malignant
      progression of prostate cancer through its anti-apoptotic action following
      androgen withdrawal. These findings support that adjuvant therapy targeting
      clusterin may enhance androgen ablation therapy in advanced prostate cancer.

PMID- 15854359
TI  - [Eversion carotid endarterectomy for carotid stenosis].
AB  - OBJECTIVE: To observe the effect of using eversion carotid endarterectomy (eCEA)
      for carotid stenosis. METHODS: Twenty four patients with carotid stenosis
      (stenosis grade 65% approximately 95%), of which 18 were symptomatic and 6 were
      asymptomatic, were treated by eCEA under regional anesthesia. All patients
      underwent preoperative cervical duplex and DSA, CT or MRA scanning examination.
      The eversion technique involved an oblique transection of the internal carotid
      artery at the carotid bulb and a subsequent endarterectomy by everting the
      internal carotid artery over the atheromatous plaque. RESULTS: There was no
      perioperative mortality and stroke. Transient ischemic attacks (TIA) disappeared,
      cerebral ischemia symptom improved in our patients. But there were mini chronic
      symptom of cerebral ischemia in 4 patients with both carotid arterial stenosis.
      CONCLUSION: Carotid eversion endarterectomy appears to be a universally
      applicable, safe, and durable operative technique.

PMID- 15854360
TI  - [Treatment of the infrequent complications after stent graft placement for aortic
      disease].
AB  - OBJECTIVE: To explore the infrequent complications and treatment after
      endoluminal stent graft implantation for aortic diseases. METHODS: Review of the
      characters and complications for five cases of aortic diseases by stent graft
      implantation. RESULTS: The complications of 4 cases have been relieved by
      operation or re-stent implantation, 1 case was died. CONCLUSION: The
      complications are difficult to forecast for stent graft placement in aortic
      diseases, the surgeon should be well practiced in surgical and interventional
      technique, so as to treat the complications in time.

PMID- 15854361
TI  - [Surgical treatment of abdominal aortic aneurysms in octogenarians].
AB  - OBJECTIVE: To evaluate the open surgery as well as the endovascular treatment of
      abdominal aortic aneurysms (AAA) in octogenarians. METHODS: Twenty AAA cases
      aging from 80 to 90 in the past six years were reviewed. Open surgery on 12
      patients and endovascular repair on the other 8 ones were performed. RESULTS:
      During peri-operation, there were 2 mortality from the surgical group among all
      20 cases. The endovascular group underwent significantly better operational
      procedure and complication situation than the surgical one. Eighteen cases were
      followed up for 3-69 months (average months) except for 2 patients of surgical
      group. Both group suffered 2 late mortality. The accumulated survival rate were
      6/10 in the surgical group and 6/8 in the endovascular group, respectively.
      CONCLUSION: Surgical treatment in applicable for octogenarians with AAA. The
      endovascular repair was preferable to suitable cases.

PMID- 15854363
TI  - [Latest cognition of treatment on deep vein thrombosis of lower extremity].
AB  - OBJECTIVE: To explore the effects of surgical procedure combined with the
      intravascular minimal invasive technique for the treatment of deep vein
      thrombosis (DVT) of lower extremity. METHODS: At the curse of disease from six
      hours to ninety days, one hundred and two patients with DVT including one hundred
      and three lower extremities had received surgical procedure and intravascular
      minimal invasive treatment. RESULTS: There were not procedure-related morbidities
      in 102 cases, and symptoms disappeared, all procedures were successful based on
      angiography. The detecting head for the intravascular ultrasound ablation was
      entered to inferior vena cava (IVC) in 74 cases (78%), Forgarty catheter was
      entered to IVC in 21 cases (21%), the stenosis in the confluence of the common
      iliac vein and IVC was dilated by sacculus rotundus catheter in 89 cases (88%),
      including 9 patients underwent percutaneous transluminal stenting. One hundred
      and two patients followed up for twenty months, follow-up by angiography showed
      no restenosis in 91 cases, restenosis in ilio-femoral vein in 1 cases, and
      thrombus recontouring in 4 cases, as well as 6 cases died caused by primary
      disease. CONCLUSION: Surgical procedure combined with the intravascular minimal
      invasive technique is a safe and effective therapeutic method for DVT.

PMID- 15854364
TI  - [To resolve the difficulties of entering into the aortic dissections' true lumen
      in endovascular graft exclusion].
AB  - OBJECTIVE: To review the methods about resolving the difficulties of entering
      into the aortic dissections' true lumen in endovascular graft exclusion. METHODS:
      The patients who had Stanford B type thoracic aortic dissection and been treated
      with endovascular graft exclusion from September 1998 to February 2004 were
      reviewed. The operations performed under DSA surveillance. In the operation, the
      wire was difficult to enter into the true lumen of the aortic dissection in 28
      cases, and was wrong into the false lumen then into the true lumen in 4 cases.
      Five methods were used to resolve these problems, including catheter smoking
      technique, different position projection, left brachial artery puncture proximal
      guide-wire floating technique, arterial choice of entering into the true lumen
      and guide-wire transfixion between proximal and distal. RESULTS: The method of
      catheter smoking technique was used in 32 cases, different position projection in
      12 cases, left brachial artery puncture proximal guide-wire floating technique in
      10 cases, arterial choice of entering into the true lumen in 28 cases, and guide
      wire transfixion between proximal and distal in 2 cases. The wires were
      ultimately successful to enter the true lumen and the stent-grafts excluded
      successfully the tears of the aortic dissections in 32 cases. CONCLUSION: The
      difficulty of entering into the true lumen and the wrong way into the false lumen
      could lead to losing the operation, even a disaster. The problem could be
      resolved by some methods of endovascular techniques.

PMID- 15854365
TI  - [The study on platelet-derived growth factor and proliferating cell nuclear
      antigen antisense oligodeoxynucleotides together inhibiting the stenosis of
      transplanted vascular].
AB  - OBJECTIVE: To study the effect of platelet-derived growth factor (PDGF) and
      proliferating cell nuclear antigen (PCNA) antisense oligodeoxynucleotides (AODN)
      together on inhibiting the proliferation of the stenosis of transplanted
      vascular. METHODS: The left and right external iliac arteries (length 1.0 cm) of
      rabbits were transplanted reciprocally. The transplanted vascular were
      respectively soaked in liposomes, PDGF-AODN, PCNA-AODN and PDGF-AODN adding PCNA
      AODN solution about 20 minute, the vascular anastomotic were sutured by 8/0
      suture of soaked in AODN solution. Four weeks later, the specimens were harvested
      for microscopy. The pathological morphology of transplanted vascular were
      observed under microscope (HE). The intimal thickness and area, stenosis ratio(%)
      of transplanted vascular were calculate and analysed statistically among group by
      computer system. The number of positive cells of PDGF's mRNA in transplanted
      vascular wall were counted with in situ hybridization histo-cytochemistry and the
      number of positive cells of PCNA's protein in transplanted vascular wall were
      counted by S-P immunochemistry. RESULTS: The intimal thickness and area, stenosis
      ratio of transplanted vascular, the number of PDGF and PCNA positive cell in PDGF
      AODN adding PCNA-AODN group were significantly lower than those in other group (P
      < 0.01), and that were lower evidently than PDGF-AODN group and PCNA-AODN group.
      CONCLUSION: PDGF and PCNA antisense oligodeoxynucleotides together could
      significantly inhibit the proliferation of vascular smooth muscle cell and
      stenosis of transplanted vascular.

PMID- 15854366
TI  - [The effect of examination of enzymes in serum to diagnosis of acute mesenteric
      ischemia in rabbit].
AB  - OBJECTIVE: To study the change regulation of enzymes in serum for the diagnosis
      and treatment of acute mesenteric ischemia by earlier period. METHODS: Thirty-six
      of rabbits were divided into three groups included from artery, vein and artery
      with vein by interrupted in mesenteric vessels respectively and there was twelve
      rabbits in every groups. It was observed that ALT, AST, ALP, gamma-GT, CK, CK-MB,
      LDH in serum at mesenteric vessels pre-interrupted and post-interrupted 1, 3, 6,
      9 h respectively and the bowel color variety was observed at the same time too.
      RESULTS: After 3 h from post-occluded of mesenteric vessels, among the three
      groups there was bowel infarction and ALT, AST, ALP, gamma-GT, LDH in serum all
      to obviously go up. CONCLUSION: It is beneficial to diagnosis of acute mesenteric
      ischemia at earlier by the examination of enzymes in serum.

PMID- 15854367
TI  - [The effects of portal vein microscopic and macroscopic tumor thrombi on post
      operation patients with hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the effects of portal vein microscopic and macroscopic
      tumor thrombi on post-operation patients with hepatocellular carcinoma (HCC).
      METHODS: Three thousand three hundred and forty eight HCC patients were
      retrospectively reviewed, which were divided into no portal vein tumor thrombi
      (PVTT), microscopic PVTT and macroscopic PVTT groups according to the pathology,
      effects of portal vein microscopic and macroscopic tumor thrombi on post
      operation patients's survival were studied by univariate analysis and overall
      survival was evaluated in each group. RESULTS: Hazard ratio (HR) of portal vein
      microscopic tumor thrombi and macroscopic tumor thrombi was 1.421 and 3.136
      respectively; The overall 1-, 3-, 5- and 10-year cumulative survival rate was
      85.97%, 62.78%, 49.88% and 35.42% respectively, and mean time for survival was
      59.7 months in group without PVTT, while 74.42%, 51.66%, 39.25% and 27.28%
      respectively and mean time for survival 39.1 months in group with microscopic
      PVTT, 52.59%, 25.97%, 20.42% and 11.33% respectively and mean time for survival
      13.5 months in group with macroscopic PVTT. CONCLUSIONS: PVTT was an important
      prognostic factor for survival in post-operation patients with HCC while
      macroscopic PVTT was more danger than microscopic PVTT. The period of microscopic
      PVTT was the landmark affecting post-operation survival.

PMID- 15854368
TI  - [Treatment and surgery of primary hepatic cancer with portal vengus tumor
      thrombosis].
AB  - OBJECTIVE: To study the methods of surgery for hepatocellular carcinoma (HCC)
      with tumor thrombi in portal vein (TTPV). METHODS: To Analyze and summarize the
      clinical information from 138 HCC patients with tumor thrombi in portal vein
      collected during January 1990 and January 2003. RESULTS: Thirty-seven patients
      receiving palliative therapy died from 1 to 8 months, and average survival time
      is 3.9 months. 101 patients had operation treatment, 23 of them underwent
      hepatoma resection, and average survival time was 10.9 months; 78 patients
      underwent hepatoma resection and removal of tumor thrombi, and average survival
      time was 26.8 months. 52 of whom underwent hepatic artery and portal vein
      chemoembolization, the 1-, 3-, 5-year survival rates was 96.2%, 51.9%, 11.5%, the
      1-, 3-, 5-year survival rates of the 26 patients who didn't undergo
      chemoembolization were 76.9%, 23.1%, 0%. CONCLUSIONS: Operation treatment can
      comparatively extend the survival time of hepatocellular carcinoma with tumor
      thrombi in portal vein patients, and the best choice is hepatoma resection and
      removal of tumor thrombi, hepatic artery and portal vein chemoembolization after
      operation can enhance the effect.

PMID- 15854369
TI  - [Cryohepatectomy for liver cancer: preliminary evaluation of reducing
      postoperative recurrence].
AB  - OBJECTIVE: To determine whether cryohepatectomy is potentially beneficial in
      reducing the recurrence and prolonging survival for hepatocellular carcinoma
      (HCC). METHODS: The study included 84 patients who underwent cryohepatectomy,
      cryosurgery with liquid nitrogen (-196 degrees C) followed by the resection of
      the frozen tumor by conventional technique, for HCC and were closely follow-up
      after surgery. Recurrence and survival rates were calculated by the life-table
      method. RESULTS: The postoperative course of cryohepatectomy in all of the 84
      patients was uneventful, there being no operative mortality or severe
      complications. The 1-, 3-, and 5-year survival rates after cryohepatectomy were
      98.7%, 83.9% and 64.0%, respectively. The 1-, 3-, and 5-year recurrence rates
      after cryohepatectomy were 15.1%, 30.1% and 39.0%, respectively. CONCLUSIONS:
      Cryohepatectomy for HCC is a safe procedure and may be potentially beneficial in
      reducing recurrence and prolonging survival. More time is needed to further
      define whether this procedure will improve long-term survival as compared with
      conventional resection.

PMID- 15854370
TI  - [Role of united hepatectomy and splenectomy in the surgical treatment of
      hepatocellular carcinoma complicated with hepatic cirrhosis and hypersplenism].
AB  - OBJECTIVE: To investigate the role of united hepatectomy and splenectomy in the
      surgical treatment of hepatocellular carcinoma complicated with hepatic cirrhosis
      and hypersplenism. METHODS: Two hundred and four patients of hepatocellular
      carcinoma complicated with liver cirrhosis and hypersplenism were divided into
      two groups: the group of combined resection of hepatocellular carcinoma and
      spleen (group A, n = 94) and the group of hepatectomy only (group B, n = 110).
      The counts of white blood cell and platelet, total serum bilirubin levels,
      changes of immune function, operative morbidity and 5-year survival rates were
      compared between the two groups. RESULTS: (1) There was no significant difference
      of the counts of CD4, CD8, CD4/CD8 and the levels of IL-2, IFN-gamma and IL-10
      between the two groups before the operation. (2) Two months after operation, the
      percentage of CD4 and the ratio of CD4/CD8 were significantly higher in the group
      A [(40.8 +/- 4.1)% and (1.8 +/- 0.2)%, respectively] than those of group B [(33.8
      +/- 3.6)% and (1.1 +/- 0.3)%, respectively], while the percentage of CD8 was
      (25.8 +/- 3.8)% in the group A, significantly lower than that of group B [(32.9
      +/- 4.1)%, P < 0.05]; Both the levels of IFN-gamma and IL-2 were significantly
      higher in the group A than those of group B while the level of IL-10 in group A
      was lower compared with that of group B (P < 0.05). (3) On the 14 postoperative
      day, the counts of white blood cell and platelet were (9.1 +/- 1.4) x 10(9)/L and
      (310 +/- 55) x 10(9)/L, which were significantly higher than those of group B
      [(3.6 +/- 1.2) x 10(9)/L and (99 +/- 36) x 10(9)/L, respectively]. (4) On the 7th
      postoperative day, the total serum bilirubin concentration of group A [(24 +/- 7)
      micromol/L] was lower than that of group B [(37 +/- 13) micromol/L]. (5) There
      was no significant difference in the postoperative morbidities between the two
      groups (15.9% and 14.5%, respectively). (6) There was no significant difference
      of the 5-year cumulative survival rates between group A (56.4%) and group B
      (50.9%, P > 0.05), but the survival rate without tumor of group A was 37.7%,
      higher than that of group B (18.9%, P < 0.05). CONCLUSIONS: The combined
      resection of hepatocellular carcinoma and spleen for the hepatocellular carcinoma
      complicated with liver cirrhosis and portal hypertension may promote the recovery
      of the balance between the subgroup of T cell and B cell, normalize the counts of
      white blood cell and platelet, alleviate the bilirubin burden and benefit for the
      recovery of liver physiological role without increase; the 5-year disease-free
      survival rate was improved significantly while no increase of postoperative
      morbidity. Combined resection may also be helpful for the delay of the
      progression of liver cirrhosis and for the prevention of esophageal variceal
      bleeding.

PMID- 15854371
TI  - [The analysis for the variation of hepatic arteries of the donor livers].
AB  - OBJECTIVE: To investigate the variations type of hepatic artery and discuss the
      method of how to protect hepatic artery from injury during the quick harvest of
      the donor liver. METHODS: A retrospective review of the variations of hepatic
      arteries of the donor livers and the course of excision and reconstruction of 200
      donor livers was performed, and the aberrance and reconstruction method of
      hepatic arteries were summarized. RESULTS: 37 out of 200 hepatic arteries varied
      and 2 patients suffered biliary complications because of improper preservation of
      aberrant hepatic arteries. CONCLUSIONS: Most aberrant liver arteries come from
      superior mesenteric artery or left gastric artery. Proper quick harvest of
      multiple organs is the basis of the integrity of hepatic arteries, and all the
      aberrance must be reconstructed.

PMID- 15854372
TI  - [Liver transplantation for hepatocellular carcinoma: prognostic analysis of 89
      cases].
AB  - OBJECTIVE: To summarize the experience of liver transplantation (LT) for
      hepatocellular carcinoma (HCC) in one center and identify prognostic factors for
      survival. METHODS: The clinical data and survival results of 89 patients with HCC
      receiving LT from January 1999 to December 2003 were retrospectively analyzed and
      various clinicopathologic risk factors for actuarial survival and tumor free
      survival were evaluated by univariate and multivariate analysis. RESULTS: Six
      month, 1-, and 2-year survival rates were 81.8%, 55.3% and 43.7%, respectively.
      The 6-month, 1-, and 2-year tumor free survival rates were 62.4%, 35.6% and
      24.9%, respectively. The overall tumor recurrence and metastasis rate was 52.8%.
      In the univariate analysis, portal vein tumor thrombi (PVTT) (chi(2) = 15.14, P =
      0.0001), tumor size (chi(2) = 15.05, P = 0.0001), hepatic cirrhosis background
      (chi(2) = 6.14, P = 0.0132), preoperative alpha-fetoprotein (AFP) level (chi(2) =
      5.82, P = 0.0159) and histopathologic grading (chi(2) = 4.61, P = 0.0319) were
      found to be significantly associated with actuarial survival rate. Seven factors
      influencing tumor free survival included PVTT (chi(2) = 26.30, P < 0.0001), tumor
      size (chi(2) = 25.25, P < 0.0001), preoperative AFP level (chi(2) = 14.83, P =
      0.0001), histopathologic grading (chi(2) = 12.54, P = 0.0004), tumor distribution
      (chi(2) = 12.73, P = 0.0004), number of nodules (chi(2) = 9.81, P = 0.0017) and
      cirrhosis background (chi(2) = 9.76, P = 0.0018). In the multivariate Cox
      regression analysis, the prognostic factors independently associated with patient
      survival were identified to be PVTT (RR = 4.721, P = 0.001), age (RR = 3.282, P =
      0.007) and histopathologic grading (RR = 2.368, P = 0.037). For tumor free
      survival, histopathologic grading (RR = 3.739, P < 0.0001), PVTT (RR = 4.382, P =
      0.001), cirrhosis background (RR = 0.421, P = 0.011), age (RR = 2.312, P = 0.027)
      and AFP (RR = 2.301, P = 0.047) were identified as prognostic parameters.
      CONCLUSIONS: LT is a good therapeutic option for strictly selected patients with
      HCC. PVTT and histopathologic grading are the most important factors of
      predicting outcomes of HCC patients undergoing LT. Further studies should be
      strengthened to establish a reliable and feasible selection criteria and an
      optimal prognosis scoring system for LT.

PMID- 15854373
TI  - [A survey on the diagnosis and treatment of biliary tract cancers in Shanghai].
AB  - OBJECTIVE: To survey the status of diagnosis and treatment of biliary tract
      cancer in Shanghai. METHODS: A clinical epidemiology investigation was carried
      out on 658 new cases of biliary duct cancers aged 35-74, that registered between
      June 1997 and May 2001 in urban Shanghai. Clinical findings were collected in 390
      gallbladder cancer, 195 bile duct cancer and 73 ampullary cancer. RESULTS:
      Biliary tract cancers mainly occurred in elderly patients. Ratio of males to
      female was 1:2.61 in gallbladder cancer, while bile duct cancer and ampullary
      cancer were slightly more common in men. Association with gallstones was 68.5%,
      43.1% and 22.4% for gallbladder cancer, bile duct cancer and ampullary cancer,
      respectively. Diagnostic accuracy rate of B-ultrasonography was 63.1% in
      gallbladder cancer. Incidental gallbladder cancer accounted for 20%, while stage
      IVA and IVB patients reached up to 43.6%. Misdiagnosis rate was still high in
      bile duct cancer and ampullary cancer, it was 19.1% and 47.1% respectively. In
      addition, most patients presented jaundice at diagnosis. 69 cases (18.2%) of
      gallbladder cancer, 50 cases (25.6%) of bile duct cancer and 54 cases (74%) of
      ampullary cancer underwent radical resection, the 1-, 3- and 5-year survival
      rates were 58.5%, 42.8% and 40.7%, 58%, 28.3% and 11.1%, 81.5%, 39.2% and 26.9%,
      respectively. 79 patients with bile duct cancer underwent palliative drainage,
      and most cases died within 1 year. Metal endo-prostheses or plastic stents were
      placed into the biliary tract in 38 patients. The median survival was about 7
      months. CONCLUSIONS: It is difficult to make early diagnosis of biliary tract
      cancers. Standardization of the operation for gallbladder cancer must be
      respected. Surgical exploration should be undertaken when a bile duct cancer is
      suspected and there are no contraindications to surgery. Pancreatoduodenectomy
      should be recommended for ampullary cancer.

PMID- 15854374
TI  - [Analysis of the treatment of unexpected gallbladder cancer].
AB  - OBJECTIVE: To investigate the secondary operation methods and the effects on the
      prognosis of unexpected gallbladder cancer (UGC). METHODS: A retrospective
      analysis on the clinical data was made for 41 patients who underwent extended
      radical excision from June 1995 to December 2002. Among the patients, 12 were
      male, 29 were female. The average age was 51 years old. The 41 patients had
      undergone gallbladder excision because of cholecystitis complicated lithiasis of
      gallbladder (32 cases), polypi of gallbladder or adenoma (9 cases). Postoperative
      pathology showed that 32 cases were adenocarcinoma of gallbladder, 6 cases were
      squamous carcinoma, 3 cases were squamous adenocarcinoma. Six cases were on the
      stage of Nevin I, 16 on Nevin II, 17 on Nevin III, 2 on Nevin IV. The second
      operation was performed after 6-30 d of the first operation. The second operation
      chose the improved method of Glenn excision of carcinoma of gallbladder. RESULTS:
      On the second operation, 14 cases were with lymphatic metastasis, 14 with
      gallbladder metastasis, 6 with bile duct metastasis, 2 with pancreas metastasis.
      Fourteen cases were on the stage of Nevin IV, 9 on Nevin V, none on Nevin I, II
      and III. After the second operation, 1 year survival rate was 100% (41 cases);
      The three-year survival rate was 53.8% (22 cases); The five-year survival rate
      was 17.5% (7 cases). CONCLUSION: Extended radical excision is one of the most
      important methods for the treatment of UGC.

PMID- 15854382
TI  - [How should we evaluate the status of pulmonary function in respiratory
      medicine?].

PMID- 15854376
TI  - [Perioperative cortisol circadian secretion and neuropsychological states in
      patients undergoing coronary artery bypass grafting surgery].
AB  - OBJECTIVE: To investigate the relationship between the circadian rhythm of
      perioperative cortisol secretion and neuropsychological states in patients
      undergoing coronary artery bypass grafting surgery. METHODS: Forty male patients
      scheduled for elective coronary artery bypass grafting (CABG) under hypothermic
      cardio-pulmonary bypass (CPB) or off-pump were enrolled in this study. They were
      allocated into CPB group or off-pump group with 20 patients in each group. Blood
      samples were withdrawn during surgery at specific time-points and every 3 h for
      24 h in the immediate postoperative period. Plasma cortisol was measured by
      radioimmunoassay. All subjects were investigated preoperatively as well as 7 to
      10 d and 3 months postoperatively with a comprehensive neuropsychologic
      assessment, while depression and anxiety were assessed by Self-Rating Depression
      Scale and the State-Trait Anxiety Inventory respectively. RESULTS: During
      postoperative 24 h, three patients in the CPB group and 7 patients in the off
      pump group were demonstrating a circadian secretion pattern, while they were
      disturbed in the remaining patients in both groups. Postoperative depression
      scores of patients in both groups were significantly higher than preoperative
      values. Postoperative anxiety scores of patients in the CPB group were
      significantly higher than those in the off-pump group. The CABG with CPB patients
      showed a significant deficit in the Digit Span subtest of the WAIS-R and the
      Stroop colour word interference test. The disturbed cortisol circadian secretion
      in the CPB group correlated with depression and the Stroop colour word
      interference test, whereas in the off-pump group it correlated with depression,
      Digit Span subtest (forward), symbol digit modalities test and the Stroop colour
      word interference test. Degree of depression correlated with some items of
      cognitive dysfunctions. CONCLUSION: Perioperative secretion rhythm of cortisol in
      patients undergoing CABG surgery with CPB or off-pump was disturbed. The
      disordered cortisol may correlate directly or indirectly through mood with
      neuropsychological deficits.

PMID- 15854383
TI  - [Intrinsic positive end-expiratory pressure should be well-recognized in clinical
      practice].

PMID- 15854387
TI  - [The effect of montelukast, a leukotriene antagonist, on improvement of exercise
      induced bronchoconstriction].
AB  - OBJECTIVE: To study the efficacy of montelukast, a cysteinyl leukotriene receptor
      antagonist, in the treatment and prevention of exercise-induced
      bronchoconstriction (EIB) in mild asthmatic patients and patients with exercise
      induced asthma (EIA). METHODS: Thirty mild asthmatic patients with positive
      standardized exercise challenge test were enrolled. The subjects received
      montelukast 10 mg once daily in the evening. Standard exercise challenge was
      performed before, three days and twenty-eight days after the administration of
      the drug. The end points included: (1) Area under the percent fall in forced
      expiratory volume in one second (FEV1) versus time curve (AUC0 to approximately
      60 min); (2) Time of recovery to within 5% of the pre-exercise baseline FEV1
      value; and (3) Maximal percent fall in FEV1 from pre-exercise baseline. RESULTS:
      Montelukast caused significant reduction in AUC0 to approximately 60 min, which
      was (39 +/- 21)%.min before treatment as compared to (13 +/- 14)%.min and (12 +/-
      14)%.min three days and twenty-eight days respectively after the treatment with
      montelukast. Time of recovery to within 5% of the pre-exercise baseline FEV1
      value were (51 +/- 36) min, (26 +/- 28) min and (25 +/- 33) min respectively. The
      mean maximal percentage decrease in FEV1 after exercise was 44.4% before
      treatment, 26.8% and 18.2% following montelukast. FEV1 and peak expiratory flow
      rate (PEFR) were maintained to nearly normal during all the study. Inhale
      corticosteroid did not prevent EIB/EIA. CONCLUSION: Montelukast attenuates and
      protects against EIB/EIA.

PMID- 15854388
TI  - [The long term effect of small dose budesonide turbuhaler on mild bronchial
      asthma].
AB  - OBJECTIVE: To investigate the long term efficacy as well as the side-effects of
      small dose budesonide turbuhaler in mild bronchial asthma. METHODS: Fifty-two
      patients with mild asthma were randomly divided into groups A, B and C. Twenty
      two cases in group A received 200 microg budesonide turbuhaler by inhalation
      every night. Fifteen cases in group B received oral prednisone 5 mg/d and
      theophyllin control release tablet 0.2 g twice daily, as well as ventolin aerosol
      inhalation 200 microg three times daily during asthmatic attack. Fifteen cases in
      group C received no glucocorticoids, but theophyllin control release tablet 0.2 g
      twice daily as well as ventolin aerosol inhalation (200 microg/d) were given
      during asthmatic attack. All three groups received treatment consecutively for 3
      years, and followed for one year after stopping treatment. During the total 4
      years, pulmonary function measurements (FEV1, Raw, Gaw), bronchial
      hyperreactivity (BHR), clinical effects, plasma cortisol level and the activated
      reaction of ACTH were evaluated. RESULTS: (1) Before the treatment, BHR of the
      three groups were similar, with most cases graded III-IV, being 91% (20/22), 100%
      (15/15) and 93% (14/15) respectively. After the treatment, the BHR of 18 (82%)
      cases of group A was reduced to grades I-II. However, 13 cases (87%) of group B
      still remained at grades III-IV and 15 cases (100%) of group C were still at
      grades III-IV. The results of the three groups showed a significant difference (P
      < 0.01). (2) Compared to measurements before the treatment, Raw was (623 +/-
      103)% vs (158 +/- 24)% in group A, (605 +/- 90)% vs (340 +/- 61)% in group B, and
      (638 +/- 108)% vs (420 +/- 81)% in group C, the difference among the three groups
      being significant (P < 0.01). (3) Compared to the measurements before the
      treatment, Gaw was (22 +/- 4)% vs (83 +/- 15)% in group A, (27 +/- 6)% vs (42 +/-
      9)% in group B, and (27 +/- 5)% vs (31 +/- 6)% in group C, the difference among
      the three groups being significant (all P < 0.01 respectively). (4) Compared with
      the measurements before the treatment, FEV1 was (2.3 +/- 0.4) L vs (2.9 +/- 0.4)
      L in group A, (2.3 +/- 0.4) L vs (2.6 +/- 0.4) L in group B, and (2.3 +/- 0.4) L
      vs (2.7 +/- 0.4) L in group C, the difference among the three groups being
      significant (P < 0.01). (5) With asthmatic symptom control as the criteria of
      therapeutical effects, the effective rate of group A, B and C were 91%, 53% and
      33% respectively, which showed significant difference among the three groups (all
      P < 0.01 respectively). (6) The plasma cortisol levels of group A and B were (326
      +/- 103) nmol/L and (308 +/- 29) nmol/L before treatment, compared with (318 +/-
      78) nmol/L and (299 +/- 98) nmol/L after treatment, the difference in group A or
      in group B was not significant (all P > 0.05). When the measurements before and
      after treatment were compared, the cortisol levels of group A and B were (365 +/-
      102) nmol/L vs (373 +/- 102) nmol/L and (343 +/- 79) nmol/L vs (346 +/- 103)
      nmol/L respectively after the stimulation of ACTH, which showed no significant
      changes even after the stimulation of ACTH (all P > 0.05). CONCLUSIONS: Long term
      small dose budesonide turbuhaler inhalation could effectively decrease BHR and
      the Raw, while increase the Gaw of asthmatic patients, hence improving the
      pulmonary function and preventing acute attack. In addition, it did not induce
      suppression of HPAA axis function in the patients.

PMID- 15854389
TI  - [Effect of chronic intermittent hypoxia on hypoxia inducible factor-1alpha in
      mice].
AB  - OBJECTIVE: To explore the mechanism of the effect of chronic intermittent hypoxia
      (CIH), an important pathophysiological state of sleep apnea syndrome (SAS), on
      cardiovascular system. METHODS: Thirty male ICR mice were divided into three
      groups: an experimental group, an air mimic control group and a blank control
      group. Immunohistochemistry was used to examine the expression of hypoxia
      inducible factor-1alpha (HIF-1alpha) and inducible nitric oxide synthase (NOS-2)
      in the myocardial cells. Enzyme-linked immunosorbent assay (ELISA) was used to
      measure the plasma concentration of vascular endothelial growth factor (VEGF) and
      endothelin-1 (ET-1). RESULTS: The expression of HIF-1alpha in myocardial cells of
      the experimental group significantly increased compared with that of the air
      mimic control group (t = 3.54, P < 0.05), and that of the blank control group (t
      = 2.92, P < 0.05). The expression of HIF-1alpha in myocardial cells of the air
      mimic control group was not significantly different from that of the blank
      control group (P > 0.05). The plasma concentration of VEGF of the experimental
      group [(9.57 +/- 1.41) ng/ml] was significantly higher than that of the blank
      control group [(8.10 +/- 0.62) ng/ml, q = 4.27, P < 0.05], and that of the air
      mimic control group [(8.32 +/- 0.99) ng/ml, q = 3.64, P < 0.05]. While the plasma
      concentration of ET-1 of the experimental group [(3.31 +/- 0.81) ng/ml] was
      significantly higher than that of the blank control group [(2.50 +/- 0.72) ng/ml,
      q = 3.64, P < 0.05], it was not significantly different from that of the air
      mimic control group [(2.69 +/- 0.43) ng/ml, P > 0.05]. There was no significant
      difference between the expression of NOS-2 in myocardial cells of all groups (P >
      0.05). CONCLUSION: CIH enhances the expression of HIF-1alpha and its target gene
      products VEGF and ET-1, and therefore affects the cardiovascular system.

PMID- 15854390
TI  - [Changes of the activity and expression of gamma-glutamylcysteine synthetase in
      patients with chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To investigate the oxidative/antioxidative status in patients with
      chronic obstructive pulmonary disease (COPD), and to study the expression and
      location of gamma-glutamylcysteine synthetase (gamma-GCS) in lung tissues.
      METHODS: (1) Serum samples of 13 patients with COPD in exacerbation and 9 healthy
      non-smokers were collected for measurements of the level of reduced glutathione
      (GSH), reactive oxygen species (ROS), total antioxidative capacity (T-AOC) and
      gamma-GCS activity. (2) Lung tissues from 22 patients (12 patients with COPD and
      10 patients as control) undergoing resection for lung tumor were collected for
      study of the expression and location of gamma-GCS and gamma-GCS mRNA by
      immunohistochemistry and in situ hybridization, respectively. RESULTS: (1)
      Significantly decreased level of GSH [(23.87 +/- 3.86) mg/ml], increased level of
      ROS [(2 463 +/- 199) U/ml], decreased T-AOC [(5.34 +/- 0.22) U/ml] and enhanced
      activity of gamma-GCS [(19.22 +/- 3.36) U/ml] were shown in the serum of patients
      with an acute exacerbation of COPD, as compared to the control group [(36.87 +/-
      6.34) mg/ml, (1 023 +/- 112) U/ml, (11.36 +/- 1.07) U/ml and (12.37 +/- 2.96)
      U/ml, respectively, all P < 0.05]. (2) There was no relationship between the
      level of GSH, ROS, T-AOC, gamma-GCS activity in serum and FEV1%, FEV1/FVC, PaO2,
      PaCO2 of patients with COPD in exacerbation (P > 0.05). (3) In situ hybridization
      showed that the expressions of gamma-GCS mRNA in alveoli, bronchi and
      inflammatory cells (A value was 0.29 +/- 0.05, 0.31 +/- 0.05 and 0.28 +/- 0.06,
      respectively) from the COPD group were stronger than those from the control group
      (0.14 +/- 0.03, 0.17 +/- 0.04 and 0.20 +/- 0.05, respectively) by semi
      quantitative analysis (all P < 0.05). (4) By immunohistochemistry, the
      expressions of gamma-GCS was significantly higher in alveoli (0.20 +/- 0.04),
      bronchi (0.18 +/- 0.02) and inflammatory cells (0.25 +/- 0.06) in the COPD group
      as compared to the control group (0.12 +/- 0.04, 0.10 +/- 0.03 and 0.14 +/- 0.04,
      respectively, all P < 0.05). (5) Negative correlations were shown between gamma
      GCS and FEV1%, FEV1/FVC (r = - 0.501 and - 0.542, respectively, P < 0.05), while
      the level of gamma-GCS expression had no correlation with FEV1% and FEV1/FVC (r =
      - 0.221 and - 0.148, respectively, P > 0.05), and a positive relationship was
      observed between gamma-GCS and gamma-GCS mRNA (r = 0.732, P < 0.05). CONCLUSIONS:
      Systemic oxidative/antioxidative imbalance occurs in patients with acute
      exacerbation of COPD, and the total antioxidative capacity decrease may not
      correlate significantly to the obstruction of airways, in spite of the high level
      of gamma-GCS activity in serum and gamma-GCS expression in the lungs.

PMID- 15854392
TI  - [Relationship between the acquired multi-drug resistance of human large cell lung
      cancer cell line NCI-H460 by cisplatin selection and p53 mutation].
AB  - OBJECTIVE: To explore the role of p53 mutation in the development of acquired
      multi-drug resistance during lung cancer chemotherapy. METHODS: A resistance
      large cell lung carcinoma cell line (H460/DDP) was established by high dose (50
      micromol/L) cisplatin intermittent selection from its parental cell NCI-H460 that
      had wild type p53 (wtp53). Several multi-drug resistant proteins (MRP) including
      lung relative protein (LRP), P-gp, MRP, glutathione transferase-pi, topoisomerase
      II and P53 were checked by immunocytochemistry. Immunofluorescence was used to
      check the phosphoration of P53. p53 cDNA was amplified and sequenced. The
      H460/DDP cells were transected with plasmid pShuttle-CMV-wtp53 cDNA and
      measurement of drug sensitivity was performed after transfection. RESULTS: The
      resistance index to cisplatin and carboplatin in H460/DDP cell line was 10.21 and
      9.98 respectively, and the cell line also exhibited cross-resistance to 5
      fluorouracil, etoposide, methotrexate, adriamycin, epirubicin, bleomycin and
      novantrone, except for taxol. It was found that P53 protein translocated from
      nuclear to cytoplasm and could not phosphorate after the stimulation of
      cisplatin. LRP was expressed increasingly and other proteins showed insignificant
      changes. Sequencing showed an important insertion "t" after 277 bp on the gene
      level. H460/DDP cells transfected with plasmid pShuttle-CMV-wtp53 cDNA reversed
      partly (53.2%) the resistance to cisplatin/carboplatin, compared to the H460/DDP
      cells transfected with blank vector. CONCLUSIONS: p53 mutation induced by
      cisplatin/carboplatin might play an important role in the development of acquired
      multi-drug resistance of lung cancer chemotherapy. wtp53 substitute therapy
      during chemotherapy may be an effective method to overcome the acquired drug
      resistance.

PMID- 15854393
TI  - [The application of 18F-fluorodeoxyglucose positron emission tomography in the
      diagnosis and staging of lung cancer].
AB  - OBJECTIVE: To study the clinical value of 18F-fluorodeoxyglucose (FDG) positron
      emission tomography (PET) in the diagnosis and staging of lung cancer. METHODS:
      Ninety-four patients with lung nodular changes were examined by CT, 18F-FDG PET
      and pathology, cytology. 18F-FDG PET images were analyzed by semi-quantitative
      standard uptake value (SUV) only and (or) SUV plus visual observation. Focuses
      with a SUV > 2.5 were judged as malignant changes, while SUV < or = 2.5 was
      judged as benign. SUV plus visual analysis, based on the focal SUV, the nodular
      size and shape, and clinical data, was carried out by two nuclear doctors. CT
      imaging was interpreted by two radiological doctors. The sensitivity,
      specificity, accuracy, positive predictive and negative predictive values of 18F
      FDG PET and CT in the diagnosis, and in the evaluation of lymphatic metastasis
      and remote metastasis of lung lesions were calculated. The diagnostic efficiency
      of the two methods (SUV or visual plus SUV method) was compared. RESULTS: (1) 58
      cases were confirmed to be malignant by surgery or pathological examination,
      while 36 cases were proved benign by pathology or empirical therapy. (2) The
      sensitivity, specificity, accuracy, positive and negative predictive values were
      69%, 65%, 68%, 82% and 49% respectively for CT; and 91%, 89%, 90%, 93% and 87%
      respectively for SUV analysis; and 95%, 94%, 95%, 97% and 92% respectively for
      visual plus SUV methods. (3) Among 34 patients with mediastinal lymph node
      involvement confirmed by pathology, 18F-FDG PET detected 30 cases, while CT
      detected only 18 cases (P < 0.01). (4) 18F-FDG PET revealed 19 cases with distant
      metastases, while CT only discovered 8 cases with distant metastases. As a
      result, the therapy was modified by PET examination in 14 patients. CONCLUSION:
      18F-FDG PET imaging is of important clinical value in the diagnosis of lung
      lesions and the staging of malignancy.

PMID- 15854394
TI  - [A retrospective cohort study of the influence of time of hospital-acquired
      pneumonia onset on pathogen constitution].
AB  - OBJECTIVE: To study the influence of duration of hospitalization on etiologic
      agent and antibiotic-resistance of hospital-acquired pneumonia (HAP). METHODS:
      Cases of HAP were patients hospitalized in Fudan University Zhongshan Hospital,
      Ruijin Hospital, Beijing Hospital, Zhongshan University Affiliated Third
      Hospital, Guangzhou Medical College Affiliated Hospital and Guangdong People's
      Hospital. These patients were hospitalized from January 2001 to December 2003,
      and the diagnosis of HAP was made based on positive respiratory specimen
      cultures. Clinical data including time of HAP onset, severity of illness, risk
      factors, isolated bacteria and antimicrobial susceptibility were collected and
      analyzed. Statistical analysis was performed with the SPSS 12.0 software.
      RESULTS: A total of 562 cases of HAP were recruited, including 136 cases of early
      onset pneumonia (time of onset < or = 5 d), 326 cases of middle-onset pneumonia
      (time of onset 6 - 14 d) and 100 cases of late-onset pneumonia (time of onset >
      or = 15 d). The rate of prior antibiotic use increased from 68.4% in the early
      onset group to 88.0% in the late-onset group (P = 0.002); ICU admission increased
      from 29.4% to 46.0% (P = 0.03), and immunosuppression increased from 1.5% to 15%
      (P = 0.001). A total of 918 strains of bacteria were isolated, the most common
      pathogens being Pseudomonas aeruginosa (18.6%), Staphylococcus aureus (16.1%),
      Acinetobacter spp (16.1%), Klebsiella spp (14.4%) and Enterobacter spp (8.8%).
      Early-onset HAP were more commonly caused by Klebstella (18.3%), while the main
      etiologic agents for late-onset HAP were Pseudomonas aeruginosa (24.2%) and
      Methicillin-resistant Staphylococcus aureus (19.3%). The rates of pneumonia
      caused by Haemophilus and Streptococcus were 4.3% and 2.4% respectively in the
      early-onset cases, but none was found in late-onset cases. The antibacterial
      activity of ceftriaxone was influenced by duration of hospitalization, risk
      factors and severity of the disease. In less severe early-onset cases without
      risk factors, the sensitivity of ceftriaxone was 80%. But in severe late-onset
      cases, it was only 50%. CONCLUSIONS: There was significant difference in the
      pathogen constitution and antibiotic-resistance among early-onset, middle-onset
      and late-onset cases of HAP. The sensitivity of ceftriaxone was high in less
      severe early-onset cases without risk factors.

PMID- 15854395
TI  - [A study on the model of tuberculous pleurisy and intrapleural inflammatory and
      immunological responses in rats].
AB  - OBJECTIVE: To develop a rat model of tuberculous pleurisy and to explore the
      mechanism of intrapleural inflammatory and immunological responses. METHODS:
      Fifty Wistar rats were injected intrapleurally with 0.03 mg of standard human
      mycobacterium tuberculous bacilli H37Rv each. The rats were killed in group on
      days 1, 2, 3, 5, 7, 10, 15, 20, 30 and 60 after the day of intrapleural
      injection. The thorax was opened and the amount of pleural effusion was recorded,
      and histopathology of pleural tissues and lung tissues were observed. The white
      blood cell (WBC) count and differentials, levels of total protein (TP), glucose
      (GLU) and lactic dehydrogenase (LDH) of pleural effusions were determined.
      Pleural fluid was analyzed for the levels of soluble intercellular adhesion
      molecule-1 (sICAM-1), transforming growth factor beta1 (TGF-beta1) and interferon
      gamma (IFN-gamma) by using appropriate bioassays. Ten rats were intrapleurally
      received 2 ml of normal saline and another 10 rats received 2 ml of undiluted PPD
      solution each as control. RESULTS: Bilateral pleural effusions appeared within 15
      days in all rats intrapleurally received tuberculous bacilli. The peak amount of
      pleural fluid was on day 5 (6.7 +/- 0.5 ml). The neutrophils were the predominant
      cells for the first 24 hours, and then were followed by lymphocytes. In the
      pleural fluid, total protein concentration was between 51-55 g/L. The levels of
      glucose and LDH were 5.2 mmol/L and 18.1 micromol.s(-1).L(-1) on day 1 and
      changed to 2.8 mmol/L and 28.9 micromol.s(-1).L(-1) on day 15 respectively. The
      biochemistry parameters were in accordance with characteristics of tuberculous
      pleurisy. The sICAM-1 level increased early (21.9 ng/ml on day 1) and peaked on
      day 3 (38.0 ng/ml), then decreased over time (4.4 ng/ml on day 15). The level of
      IFN-gamma was 41.2 pg/ml on day 1 and increased and maintained at high levels
      over time. TGF-beta1 levels increased and peaked on day 7 (47.2 ng/ml), and then
      on day 15 decreased to a level lower than that of day 1. The ratio of IFN
      gamma/TGF-beta1 increased from 1.32 on day 1 to 5.69 on day 15. Correlation
      analysis showed that sICAM-1 and IFN-gamma were closely related with WBC count
      and its differentials, as well as with LDH levels. Histopathological study
      revealed early pleural inflammation and late caseation. CONCLUSIONS: Wistar rats
      can be used as an experimental model for tuberculous pleurisy. Tuberculous
      inflammatory and immunological responses in acute tuberculous pleurisy is
      enhanced rather than suppressed.

PMID- 15854406
TI  - [Clinical significance and shortcoming of classification of asthma severity].

PMID- 15854407
TI  - [Study of genes that differentially expressed in eosinophils of patients with
      asthma by suppression subtractive hybridization technology].
AB  - OBJECTIVE: To study genes that differentially expressed in peripheral blood
      eosinophils of patient with asthmatic. METHODS: Total RNA extracted from
      eosinophils of patient at the time of exacerbation was taken as the tester and
      the total RNA from eosinophils of the same patient after improvement as driver.
      The ds cDNA was synthesized by SMART PCR cDNA Synthesis technology. The
      differentially expressed genes were obtained by suppression subtractive
      hybridization (SSH) technology and were further identified by Southern blot.
      RESULTS: Twelve differentially expressed genes including transformation growth
      factor beta activated kinase like (TAK1L) protein, cGMP gated channel protein
      were obtained. CONCLUSION: Increased expression of these genes were involved in
      the regulation of proinflammatory response, signal transduction, energy
      metabolism and cell apoptosis, which may help to clarify the molecular mechanism
      of eosinophils in asthma and may provide the theoretical base for finding out the
      new medicines towards eosinophils.

PMID- 15854408
TI  - [Effects of budesonide on airway inflammation and airway remodeling in the
      ovalbumin sensitized and challenged mice].
AB  - OBJECTIVE: To investigate the effects of budesonide (BUD) used in an early phase
      or delayed phase on the airway inflammation and airway remodeling in ovalbumin
      (OVA) sensitized and challenged mice. METHODS: Forty mice were divided into 5
      groups (8 in each group) including group A [ovalbumin (OVA) sensitized/challenged
      mice], group B (saline sensitized/challenged mice), group C (OVA
      sensitized/challenged mice treated by BUD in the early phase), group D (OVA
      sensitized/challenged mice treated by BUD in the late phase) and group E (OVA
      sensitized/challenged mice following saline challenge for 18 days). Mice were
      sensitized on days 0 and 14 by OVA and challenged from days 24 to 41 by OVA
      repeatedly to establish a murine model of asthma characterized by airway
      inflammation and airway remodeling. To assess the effects of BUD on the
      development of airway remodeling and on established airway remodeling, animals
      were treated with aerosolized BUD (0.5 mg/ml per day) from day 1 before OVA
      challenge (group C) and from day 18 following first OVA challenge (group D). The
      outcome measurements included airway inflammatory indices, eosinophils (EOS)
      count and amount of collagen deposition around the bronchus, area of airway
      smooth muscle, the degree of mucus secretion in the lumens and depth of airway
      smooth muscle (ASM) in different grade bronchus by HE, PAS and Masson's staining.
      The bronchoalveolar lavage fluids (BALF) were assayed for IL-5 and IFN-gamma
      levels. RESULTS: In repeatedly OVA-challenged mice (group A), EOS counts in BALF
      increased significantly [(57.460 +/- 11.060) x 10(4)/ml] when compared with group
      B [(0.050 +/- 0.020) x 10(4)/ml, P < 0.01]. The IL-5 level increased
      significantly [(52.9 +/- 2.8) pg/ml vs (16.8 +/- 1.5) pg/ml, < 0.01] and IFN
      gamma decreased significantly [(39.5 +/- 3.2) pg/ml vs (63.8 +/- 3.3) pg/ml, <
      0.01]. Repeatedly OVA-challenged animals (group A) also developed an increase in
      EOS counts around bronchus [(1 018 +/- 118)/mm(2)] when compared with group B [(7
      +/- 3)/mm(2), < 0.01], goblet cell hyperplasia [(46.0 +/- 5.8)% vs (1.8 +/-
      0.5)%, < 0.01] and mucus hypersecretion [(score 2.98 +/- 0.23) vs (score 0.13 +/-
      0.06), < 0.01], airway smooth muscle hypertrophy [(30.2 +/- 2.2)/microm(2)/microm
      vs (13.1 +/- 1.0) microm(2)/microm, < 0.01], enhanced collagen deposition of
      reticular basement membrane (RBM) [(24.9 +/- 1.3) microm(2)/microm vs (4.3 +/-
      0.6) microm(2)/microm, all < 0.01]. Early treatment with BUD significantly
      reduced EOS counts in BALF [(7.140 +/- 1.250) x 10(4)/ml] as compared with group
      A [(57.460 +/- 11.060) x 10(4)/ml], < 0.01]. Early BUD treatment also
      significantly reduced EOS counts around bronchus [(214 +/- 26)/mm(2)], allergen
      induced structural changes including goblet cell hyperplasia [(16.1 +/- 2.5)%]
      and mucus hypersecretion (1.10 +/- 0.15), airway smooth muscle hypertrophy [(14.0
      +/- 0.7) microm(2)/microm], and RBM collagen deposition [(12.6 +/- 1.3)
      microm(2)/microm]. In group E, EOS counts in BALF [(1.250 +/- 0.330) x 10(4)/ml]
      were decreased significantly when compared with group A (< 0.01), but airway
      smooth muscle hypertrophy [(32.4 +/- 1.8) microm(2)/microm], and RBM collagen
      deposition [(22.8 +/- 1.7) microm(2)/microm] showed no reduction as compared with
      group A (all P > 0.05). Delayed BUD treatment significantly reduced EOS counts in
      BALF [(0.800 +/- 0.170) x 10(4)/ml], goblet cell hyperplasia [(29.3 +/- 4.3)%]
      and mucus hypersecretion (1.63 +/- 0.17, < 0.05 or < 0.01), but had no effects on
      OVA-induced airway smooth muscle hypertrophy [(30.1 +/- 1.8) microm(2)/microm]
      and RBM collagen deposition [(23.7 +/- 1.4) microm(2)/microm] as compared with
      group A (P > 0.05). CONCLUSIONS: Early treatment with BUD inhibited the
      development of airway inflammation of airway remodeling. However, delayed use
      with BUD inhibited airway inflammation, but only partially reversed airway
      remodeling in a murine model of asthma.

PMID- 15854409
TI  - [A study of interferon-gamma induced airway mucous cell apoptosis and its
      mechanisms].
AB  - OBJECTIVE: To investigate the effect of interferon-gamma (IFN-gamma) on airway
      mucous cells and its mechanisms. METHODS: (1) Normal human bronchial epithelial
      cells (NHBEs) were cultured under specific conditions, and treated by IFN-gamma
      for 3 days. The cells were analyzed with fluorescein isothiocyanate (FITC) and
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
      assay. (2) Twenty wild type C57BL/6J mice were immunized and divided into 4
      groups, and treated with IFN-gamma (50 ng and 100 ng, respectively), interleukin
      13 (IL-13, 5 microg) and saline by nostril instillation. The mice were sacrificed
      and the airway mucous cells were analyzed by morphometry and TUNEL assay.
      RESULTS: (1) IFN-gamma induced apoptosis in NHBEs, which showed condensed nuclei,
      nuclear and DNA fragmentaion, and were positive by TUNEL assay. Bax was
      upregulated and translocated from cell plasma to mitochondria under the
      treatment. (2) Airway mucous cell account in 100 ng IFN-gamma instillation
      immunized mice group (28 +/- 6 mucous cells/mm basal lamina) was significantly
      decreased as compared to that in saline (58 +/- 12) and IL-13 (59 +/- 6)
      instillation groups (all < 0.05). There was no difference among the IFN-gamma 50
      ng (48 +/- 11), saline (58 +/- 12) and IL-13 (59 +/- 6) instillation groups (all
      P > 0.05). TUNEL assay was also positive in airway mucous cells from IFN-gamma
      instillation mice as compared to saline instillation mice. CONCLUSIONS: IFN-gamma
      leads to airway mucous cell apoptosis by Bax upregulating and translocation into
      mitochondria. This might be of significance in the new therapies of asthma.

PMID- 15854410
TI  - [Preliminary analysis of the 5'-flanking region of rat gamma-glutamylcysteine
      synthetase catalytic subunit gene].
AB  - OBJECTIVE: To analyze the characteristic of regulatory elements and corresponding
      transcriptional factors in the 5'-flanking region of rat gamma-glutamylcysteine
      synthetase (gamma-GCS) catalytic subunit (GCLC) gene. METHODS: A 1 760 bp 5'
      flanking region of the rat GCLC was cloned and constructed into pGL-3 enhancer
      vector which includes luciferase reporter gene. Exonuclease III was used to cut
      the 5'-flanking region of rat GCLC gene unidirectionally into deletion mutants of
      different length, GCLC-Luc and its deletion mutants were used to transfect rat
      alveolar epithelium cells CCL-149, then the regulatory region of the gene was
      determined by luciferase activity assay of the transfected cells. Analysis of the
      transcription-factor-binding site was done using Transcription Factor Search
      software to indicate possible transcriptional factors. Electrophoresis mobility
      shift assay (EMSA) was used to determine the cis-acting elements and
      transcriptional factors in these regulatory regions. RESULTS: The experiment
      cloned the upstream regulatory sequence of rat GCLC gene and its reporter vector
      GCLC-Luc, as well as 11 deletion mutants of GCLC-Luc. Luciferase activity assay
      of the cells transfected by GCLC-Luc (-1 758/+2-Luc), mutant 1 (-1 231/+2-Luc),
      mutant 2 (-1 108/+2-Luc), mutant 3 (-1 087/+2-Luc), mutant 4 (-876/+2-Luc),
      mutant 5 (-745/+2-Luc), mutant 6 (-705/+2-Luc), mutant 8 (-613/+2-Luc), mutant 9
      (-595/+2-Luc), mutant 10 (-403/+2-Luc) and mutant 11(-111/+2-Luc) were (90 012 +/
      2 445), (77 652 +/- 840), (149 927 +/- 4 915), (71 588 +/- 1 108), (99 283 +/- 2
      612), (75 443 +/- 1 438), (282 772 +/- 7 046), (96 891 +/- 2 275), (148 917 +/- 5
      966), (258 991 +/- 5 015) and (895 +/- 49) U, respectively. EMSA proved that
      activated protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) can bind to the
      region of -403 to -111 bp; nuclear factor-1 (NF-1) and CCAAT/enhancer binding
      protein (C/EBP) can bind to the region of -705 to -613 bp; and upstream
      stimulatory factor (USF) can bind to the region of -745 to -705 bp. CONCLUSIONS:
      Two DNA regions -403 to -111 bp and -705 to -613 bp of GCLC gene, which can be
      bound by transcriptional factors such as NF-1, C/EBP, AP-1, and NF-kappaB on
      EMSA, are involved in positive gene regulation. A newly identified region -745 to
      -705 bp of GCLC gene, which can be bound by USF, is involved in negative gene
      regulation, suggesting that the interaction between E-box and USF can inhibit the
      expression of gamma-GCS.

PMID- 15854411
TI  - [The changes of apoptosis and proliferation of pulmonary tissue in chronic
      obstructive pulmonary disease rats].
AB  - OBJECTIVE: To observe the changes of apoptosis and proliferation of pulmonary
      tissue cells in rats with chronic obstructive pulmonary disease (COPD). METHODS:
      The rat model of COPD was established by exposure to cigarette smoking. Thirty
      three Wistar rats were randomly divided into a normal control (NC) group, a
      smoking inhalation for 1 month (COPD-1) group and a smoking inhalation for 2
      month (COPD-2) group. Pathologic changes of lung tissues and inflammatory cell
      differentials were studied. Immunohistochemistry and terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) methods were carried out to
      examine the percentage of positive cells and distribution of apoptotic cells and
      proliferating cells in the lung tissue. RESULTS: Significant increases in total
      leukocyte numbers and neutrophils in the bronchoalveolar lavage were found in the
      COPD groups as compared to NC group. Two months after smoking exposure,
      enlargement of airspaces distal to the terminal bronchiole, destruction of
      alveolar walls, and loss of the alveolar unit were observed. The percentage of
      apoptotic cells of airway epithelium, alveolar wall cell and vascular smooth
      muscle cells were (36.2 +/- 8.5)%, (32.7 +/- 6.4)%, (16.1 +/- 7.2)% in COPD-1
      group; (39.5 +/- 9.3)%, (37.3 +/- 7.6)%, (21.4 +/- 6.5)% in COPD-2 group; the
      difference being significant (all P < 0.01), as compared with NC group [(5.8 +/-
      1.7)%, (6.1 +/- 2.3)%, (4.9 +/- 1.4)%]. The percentage of proliferative cells of
      airway epithelium, alveolar wall cell and vascular smooth muscle cells were (33.4
      +/- 6.3)%, (30.1 +/- 4.6)%, (28.4 +/- 6.3)% in COPD-1 group; (35.5 +/- 9.8)%,
      (33.2 +/- 7.7)%, (34.5 +/- 6.7)% in COPD-2 group; the difference being
      significant (all P < 0.01), as compared with NC group [(7.4 +/- 2.3)%, (5.2 +/-
      2.1)%, (4.4 +/- 1.8)%]. The numbers of apoptotic and proliferating cells were
      significantly higher in the COPD-2 group than those in the COPD-1 group (all P <
      0.01). The ratio of proliferative index (PI)/apoptotic index (AI) of the
      pulmonary tissue cells were also different. The ratio of PI/AI of airway
      epithelium in COPD-1 and COPD-2 group [(0.82 +/- 0.13)%, (0.78 +/- 0.24)%] was
      much lower than NC group [(1.12 +/- 0.23)%, P < 0.05]; The ratio of PI/AI in
      small pulmonary vessels in the COPD groups [(1.55 +/- 0.25)%, (1.47 +/- 0.28)%]
      was significantly higher than NC group [(0.92 +/- 0.05)%, P < 0.05]. CONCLUSION:
      The changes of apoptosis and proliferation of pulmonary tissue in COPD rats might
      contribute to the pathogenesis of COPD.

PMID- 15854412
TI  - [Influence of hypoxia on leptin and leptin receptor gene expression of C57BL/6J
      mice].
AB  - OBJECTIVE: To investigate the influence of hypoxia on leptin and leptin receptor
      gene expression of C57BL/6J mice. METHODS: C57BL/6J mice, exposed to hypoxia in
      the man-made auto pressure and hypoxia control cabin (XQ-I), were divided into 3
      groups: the normal control group, 24 h hypoxia group and 48 h hypoxia group.
      Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the
      mRNA levels of leptin and leptin receptor. RESULTS: (1) Compared with the normal
      control group (0.508 +/- 0.207), the leptin mRNA level of 24 h hypoxia group
      (0.903 +/- 0.190) and 48 h hypoxia group (0.856 +/- 0.336) were up-regulated
      markedly (all < 0.05); (2) Compared with the normal control group (Ra 0.630, Rb
      0.258 +/- 0.049, Rc 0.133), the Ra, Rb, Rc mRNA levels of 24 h hypoxia group (Ra
      0.724, Rb 0.381 +/- 0.038, Rc 0.299) and 48 h hypoxia group (Ra 0.700, Rb 0.345
      +/- 0.042, Rc 0.292) were up-regulated to different degrees. CONCLUSIONS: As an
      independent factor, hypoxia can stimulate increased expression of leptin, leptin
      receptor Ra, Rb, Rc mRNA. It is suggested that leptin play an important role in
      positive regulation of respiratory function.

PMID- 15854413
TI  - [Roles of mutant p53 gene in malignant phenotypes and resistance to drugs in anti
      7,8-dihydrodiol-9,10-epoxide benzo(a)pyrene-induced lung cancer cells].
AB  - OBJECTIVE: To study the role of mutant p53 gene induced by anti-7,8-dihydrodiol
      9,10-epoxide benzo(a)pyrene (BPDE) in the development of lung cancer and the
      effects of wild-type p53 substitution on malignant phenotype and resistance to
      drugs. METHODS: BPDE-induced human lung cancer cells (16HBE, a human bronchial
      epithelial cell line, treated by BPDE) with mutant p53 gene were transfected with
      pShuttle-cmv-wild p53, followed by soft-agar colony formation assay and cell
      growth assay. Genome DNAs were extracted from those cells after transfection for
      detection of apoptosis. Sensitivity of the cells to drugs was also detected
      simultaneously. RESULTS: It was shown that exogenous wild-type p53 transfection
      inhibited colony formation of the lung cancer cells with mutant p53 gene and
      induced cell growth arrest and cell apoptosis. In addition, the lung cancer cells
      transfected with wild-type p53 gene showed enhanced sensitivity to adriamycin
      (ADM) to which the cells before transfection was resistant. CONCLUSIONS: p53
      mutation plays an important role in the development and progress of lung cancer,
      as well as in multi-drug resistance in the management of lung cancer
      chemotherapy. Wild-type p53 substitution therapy may enhance the sensitivity of
      lung cancer to chemical drugs.

PMID- 15854414
TI  - [Treatment of non-small cell lung cancer with gefitinib].
AB  - OBJECTIVE: To investigate the antitumor effects and toxicity of epidermal growth
      factor receptor (EGFR)-tyrosine kinase inhibitor gefitinib (Iressa) in advanced
      non-small cell lung cancer (NSCLC). METHODS: The clinical data and quality of
      life of 66 patients with NSCLC treated with Iressa orally at the dose of 250 mg/d
      were reviewed, and the data were analyzed by using logistic analysis, chi(2) test
      and t test. The impact of treatment on disease-related symptoms and quality of
      life was evaluated with Chinese version of European Organization for Research and
      Treatment of Cancer-Quality of Life Core Questionnaire-30 (EORTC QLQ-C30) and QLQ
      LC13. RESULTS: Tumor response rate was 33%. Disease control rate, which included
      both tumor responses and stable disease, was 70%. The mean scores of each
      functioning scales and global quality of life in QLQ-C30 increased significantly.
      Response rates were 91% - 100%. Mean scores of disease-related symptoms decreased
      significantly. Response rates were 73% - 100%. Quality of life and symptom
      response were correlated with objective tumour response. The 250 mg/day dose of
      Iressa was well tolerated by patients. The majority of adverse events were grade
      I or grade II skin rash and diarrhea, which were manageable and reversible.
      CONCLUSION: Iressa offers a new treatment option providing meaningful tumor
      control and symptom relief for many patients with advanced NSCLC.

PMID- 15854415
TI  - [Cell apoptosis and the change of Fas/FasL gene in experimental pulmonary
      fibrosis].
AB  - OBJECTIVE: To investigate the changes and significance of cell apoptosis and
      Fas/FasL gene in pulmonary fibrosis. METHODS: Forty mice were divided into two
      groups randomly, each group contained twenty mice. TUNEL, immunohistochemistry
      and in situ hybridization were used to detect the change of cell apoptosis,
      Fas/FasL mRNA and protein in mice with pulmonary fibrosis caused by bleomycin.
      RESULTS: The apoptosis index of lung cells in the pulmonary fibrosis group (55.3
      +/- 12.2) was higher than that of control group (4.7 +/- 1.0, t = 13.06, < 0.01).
      The expression of Fas/FasL mRNA (175.8 +/- 21.6, 5.2 +/- 1.6) and protein (956 +/
      96, 285 +/- 76) in the pulmonary fibrosis group was higher than that of control
      group (mRNA: 26.6 +/- 1.9, 0.5 +/- 0.4, t = 21.7, 8.79, all < 0.01; protein: 491
      +/- 96, 100 +/- 18, t = 5.03, 12.81, < 0.01). CONCLUSION: The apoptosis index of
      lung cells, Fas/FasL genes and protein were up-regulated in lung tissue of
      pulmonary fibrosis, which may play an important role in the development of
      disease.

PMID- 15854416
TI  - [Knowledge of tuberculosis amongst service industry workers of the floating
      population in Changning district, Shanghai].
AB  - OBJECTIVE: To study tuberculosis related knowledge among the floating population
      who work in service enterprises in Changning District, Shanghai. METHODS: A self
      completed questionnaire interview was conducted in Nov. 2003 among 274 floating
      persons who were recruited through cluster sampling in Changning District (male
      113, female 161). RESULTS: It was found that the floating population had some
      knowledge of tuberculosis, however, the weighted marks were not high. 34.7% of
      the study subjects responded correctly to more than 60% of the knowledge
      questions, and therefore were considered to have an adequate knowledge of
      tuberculosis. Through logistic regression, education level and marriage status
      were found to be correlated with the mean weighted marks of knowledge of
      tuberculosis (chi(2) = 19.650, P < 0.01; chi(2) = 4.059, P < 0.05). It was also
      found that education level was associated with the ways of obtaining knowledge
      (chi(2) = 6.87, < 0.01). As to the expected ways of receiving health education,
      it was correlated with education level and the work place (chi(2) = 6.74, P <
      0.05; chi(2) = 17.81, < 0.05). CONCLUSION: Findings from this study reflect that
      it is important to provide health education on tuberculosis to the floating
      population in order to prevent tuberculosis infection and transmission and to
      improve the case detection of tuberculosis among the floating population in
      cities.

PMID- 15854417
TI  - [In vitro study on cross resistance of rifampin and rifapentine for Mycobacterium
      tuberculosis].
AB  - OBJECTIVE: To study the bactericidal effect of rifapentine and its cross
      resistance with rifampin for Mycobacterium tuberculosis and to determine the
      critical concentration of rifapentine for laboratory drug susceptibility test and
      therefore to provide the laboratory data for using rifapentine in the treatment
      of tuberculosis, particularly rifampin resistant tuberculosis. METHODS: We
      detected the minimal inhibitory concentrations (MICs) of rifampin and rifapentine
      to H(37) Rv and isolated strains of rifampin susceptible and resistant
      Mycobacterium tuberculosis by using Middlebrook 7H9, Sauton and Lowenstein-Jensen
      media. RESULTS: The MICs of rifampin were > or = 0.32 microg/ml for 80% of the 19
      rifampin susceptible strains on Middlebrook 7H9 and the MICs of rifapentine
      ranged from 0.02 microg/ml to 0.32 microg/ml for most of the strains (84%). The
      MICs of rifapentine were 2 - 4 times lower than those of rifampin to H(37) Rv and
      most clinical isolates. The rifapentine susceptible isolates were mostly
      separated from resistant strains at MICs 5-10 microg/ml. CONCLUSIONS: Our results
      demonstrate the cross resistance of rifampin and rifapentine and the stronger
      bactericidal potency of rifapentine than rifampin. Some rifampin resistant
      strains still show susceptibility to rifapentine, which suggests rifapentine may
      be effective in the treatment of rifampin resistant tuberculosis. Our results
      also determined a critical resistant concentration of rifapentine for routine
      drug susceptibility test.

PMID- 15854426
TI  - [Respiratory physicians should pay attention to the prevention and treatment of
      lung cancer].

PMID- 15854427
TI  - [Application of technetium-99m labelled sandostatin Somatostatin receptor imaging
      in the detection of lung cancer].
AB  - OBJECTIVE: To evaluate the clinical value of (99)Tc(m)-sandostatin receptors
      imaging ((99)Tc(m)-sandostatin) in detection of lung tumors in comparison with
      fludeoxyglucose F18 dual head coincidence imaging ((18)F-FDG DHC). METHODS: Fifty
      six consecutive patients (40 men, 16 women; mean age: 62 years, range 35 - 80
      years) with pulmonary neoplasm were referred for evaluation. All underwent
      sandostatin scintigraphy using hybrid SPECT/CT. (18)F-FDG DHC imaging was also
      performed in 23 patients using the same camera. The tumor uptake of (99)Tc(m)
      sandostatin and (18)F-FDG DHC were measured respectively and expressed as the
      ratio of T/Nr and T/Nm. Final clinical diagnosis was confirmed by
      histopathological study. RESULTS: Out of 56 cases, 46 were confirmed to be
      malignant and 10 benign. The sensitivity, specificity and accuracy of (99)Tc(m)
      sandostatin in diagnosis of lung cancer were 95.7%, 90.0%, 94.6%, respectively.
      The positive predictive value (PPR) was 97.8%, and the negative predictive value
      (NPR) was 81.8%. In the 23 patients underwent both methods, the sensitivity,
      specificity and accuracy of (18)F-FDG DHC were 100%, 60.0%, 82.6%, respectively;
      the PPR was 76.5%, and the NPR 100%. Out of 13 patients with malignant neoplasms,
      6 patients had regional lymph node metastasis, and all of 10 abnormal lymph
      nodules showed high uptake of FDG, while (99)Tc(m)-sandostatin imaging only 2
      regional metastasized lymph nodes in one patient. T/N(r) and T/N(m) were 3.15 +/-
      1.30, and 10.61 +/- 4.35 respectively. There was no relationship between
      sandostatin uptake and glucose metabolism. CONCLUSION: (99)Tc(m)-sandostatin
      scintigraphy is a promising noninvasive imaging technique for detection of the
      primary tumor of lung cancer but of limited value in the detection of lymph node
      metastasis.

PMID- 15854428
TI  - [Application of positron emission tomography in diagnosis and staging for lung
      cancer].
AB  - OBJECTIVE: To determine the usefulness of positron emission tomography with
      fluoro-2-deoxyglucose (FDG-PET) in lung cancer. METHODS: From September 1999 to
      April 2003, patients with lung cancer or indeterminate lung lesions on chest CT
      scan were enrolled, and underwent FDG-PET scanning. RESULTS: Of 104 patients, 64
      (60%) had malignancy and 40 (40%) had a benign process. The standard uptake ratio
      (SUV) in patients with lung cancer was significantly higher than that in patients
      with benign disease, 4.5 (1.2 - 11.7) and 1.0 (0 - 7.7) respectively. The SUV was
      not related with histologic type, differentiation, staging and the size of
      lesion. The diagnostic sensitivity, specificity and accuracy of PET imaging for
      lung cancer were 88%, 85% and 87% respectively, and the diagnostic specificity
      and accuracy for lung cancer with PET were significant higher than those with CT
      scan. The specificity and accuracy of lung lesions with a diameter >or= 1.5 cm
      with SUV method was better than that of lesions with a diameter < 1.5 cm. In 6
      false positive patients, 4 were tuberculosis, 1 fungal infection and 1 organic
      pneumonia. Both PET and CT scan were poorly sensitive and specific for detecting
      local lymph node metastasis. CONCLUSIONS: PET had advantages in evaluation of
      lung lesions, and integrated PET and CT were recommended for detecting local
      lymph node metastasis.

PMID- 15854429
TI  - [The expression of survivin messenger RNA in sputum and cancerous tissue in human
      lung cancer].
AB  - OBJECTIVE: To study the diagnostic significance of the expression of survivin
      mRNA in transbronchial biopy samples and sputum samples in lung cancer. METHODS:
      The resected lung cancer tissues and their para-carcinomatous normal tissue
      specimens of 41 patients with lung cancer and tissue specimens of 9 patients with
      benign pulmonary diseases were studied. 110 bronchial biopsy specimens from 80
      patients with lung cancer and 30 patients with benign pulmonary diseases and
      their 160 sputum samples were also evaluated. RT-PCR was performed for the
      detection of survivin mRNA expression in specimens. The results were compared
      with their histological or cytological examinations. RESULTS: (1) The positive
      rate of survivin mRNA in resected lung cancer tissues (29/41; 70.7%) was higher
      than that in the para-carcinomatous normal tissues (7/41; 17.1%) and the benign
      pulmonary tissues (1/9; 11.1%, P < 0.05). There was no statistical difference (P
      > 0.05) in the positive rate of survivin mRNA between para-carcinomatous normal
      tissues and the benign pulmonary disease tissues. In the bronchial biopsy
      samples, the positive rate of survivin mRNA in 80 lung cancer tissues (51/80;
      63.8%) was also higher than that in the benign pulmonary tissues (4/30; 13.3%, P
      < 0.05). There were no relationships between survivin mRNA expression and age,
      sex, histopathological subtype, differentiation, or lymph node metastases of the
      patients. The sensitivity and specificity of diagnosis for lung cancer by
      detecting survivin mRNA in resected cancer tissue and transbronchial biopsy
      tissue were 63.8% - 70.7% and 86.7% - 88.9%, respectively. (2) The sensitivity of
      cytological examinations combined with detecting survivin mRNA in sputum samples
      was higher than that of either cytological examination or survivin mRNA detection
      of sputum samples alone (P < 0.05). The sensitivity of the diagnosis for lung
      cancer increased from 47.1% (sputum cytology alone) to 80.2% (sputum survivin
      mRNA detection combined with sputum cytology, P < 0.05) and the negative
      predictive value increased from 37.9% for sputum cytology alone to 57.9% (P <
      0.01) for sputum survivin mRNA detection combined with sputum cytology. The
      specificity did not change significantly. CONCLUSIONS: Detecting survivin mRNA
      expression from bronchial biopsy specimens might be used as one of the specific
      molecular markers for diagnosis of lung cancer, while the detection of survivin
      mRNA from sputum samples as a new ancillary diagnostic method for lung cancer.

PMID- 15854430
TI  - [Cooccurrence of pulmonary tuberculosis and carcinoma: diagnosis and the
      prognostic factors for surgical effects].
AB  - OBJECTIVE: To study the association, clinical diagnosis and treatment of the
      coexistence of lung cancer and tuberculosis. METHODS: Sixty-five patients with
      coexistence of lung cancer and tuberculosis underwent surgical treatment in our
      hospital between 1954.1 and 2004.3. Twelve factors possibly influencing the
      survival were selected. A multivariate analysis of these individual variables was
      performed using the cumulative survival rate by the computer' COX proportional
      hazard model. RESULTS: Histologically, there were 41 cases of squamous cell
      carcinoma, 15 adenocarcinoma, 3 small cell carcinoma and 6 mixed carcinoma. Chest
      radiological study showed infiltrative tuberculosis in 41, military tuberculosis
      in 2, and chronic fibrocavitary tuberculosis in 22 cases. Of these, wedge
      excision was performed in 4, lobectomy in 38, bilobectomy in 4, pneumonectomy in
      17 and palliative resection in 2 patients. There was no operative mortality.
      Follow-up showed that 1-, 3- and 5-year survival was 67.7% (44/65), 35.4%
      (23/65), and 23.1% (15/65) respectively. Clinical analysis showed that the major
      significant prognostic factors influencing survival were malignancy occurred in
      local tuberculosis, the operation procedures for lung cancer, and the stage of
      lung cancer (P < 0.01). CONCLUSIONS: The occurrence of lung cancer is highly
      correlated to the site of tuberculosis. The recognize of this can facilitate the
      early diagnosis and resection of malignancy as well as the initiation of regular
      medical therapy.

PMID- 15854431
TI  - [Evaluation of the clinical efficacy and the safety of salmeterol/fluticasone
      propionate accuhaler compared to budesonide turbuhalar in the control of adult
      asthma].
AB  - OBJECTIVE: To evaluate the efficacy and the safety of low dose
      salmeterol/fluticasone (SM/FP) combination therapy as compared to morate dose of
      budesonide (BUD) in the management of adult asthma. METHODS: A multicentre,
      randomised, open-label, parallel-group, 6-week treatment study was conducted. 398
      patients (18 - 70 years) were given SM/FP (50/100 microg) twice daily via
      Accuhaler or BUD 400 microg twice daily via Turbuhaler. RESULTS: The morning and
      the evening peak expiratory flow (PEF) measurements both increased significantly
      (P < 0.01) in the SM/FP group, and the increase was greater than that in the BUD
      group. The significant benefit of SM/FP was evident from the first week. SM/FP
      led to a more significant reduction in the use of rescue medication and in the
      day- and night-time asthma symptom scores, as compared to budesonide. Both
      treatments were well tolerated, and the adverse reactions showed no significant
      difference between the two groups. CONCLUSIONS: Combination use of low doses of
      SM/FP is a better choice for the control of asthma. The addition of a low-dose
      long-acting beta(2) agonist is superior to the simple increase of the dosage of
      inhaled corticosteroids.

PMID- 15854432
TI  - [Safety of sputum induction in subjects with acute exacerbations of chronic
      obstructive pulmonary disease].
AB  - OBJECTIVE: To evaluate the safety of sputum induction in subjects with acute
      exacerbations of chronic obstructive pulmonary disease (AECOPD). METHODS: Twenty
      two patients with AECOPD were enrolled in the study. All subjects inhaled a mist
      of 3% hypertonic saline solution and the forced expiratory volume in one second
      (FEV(1)) and pulse oxygen saturation (SpO(2)) were measured during the procedure.
      RESULTS: A significant fall in SpO(2) and FEV(1) was found during sputum
      induction by inhalation of 3% hypertonic saline solution. Mean decline in SpO(2)
      during sputum induction was (2.1 +/- 0.4)% (P < 0.01) and recovered within 10 min
      after cessation of sputum induction. Mean decline in FEV(1) during sputum
      induction was (12.3 +/- 3.1)% (P = 0.027), an absolute fall of (0.11 +/- 0.03) L,
      and the FEV(1) returned to the baseline in all subjects within 10 min after
      cessation of sputum induction. The sputum induction was successful in 19 of the
      22 (86%) patients. CONCLUSION: The use of a standardized sputum induction
      protocol is relatively safe in sampling the lower airways in patients with
      AECOPD.

PMID- 15854433
TI  - [Pulmonary alveolar proteinosis treated with whole-lung lavage utilizing
      extracorporeal membrane oxygenation: a case report and review].
AB  - OBJECTIVE: To improve the treatment of severe hypoxaemia in patients with
      pulmonary alveolar proteinosis (PAP). METHODS: The clinical data of a patient
      with pathologically proven PAP treated with whole-lung lavage utilizing
      extracorporeal membrane oxygenation (ECMO) were described and the literature was
      reviewed. RESULTS: This 57-year-old man was admitted because of cough and
      progressive dyspnea for 12 months. His PaO(2) was 46 mm Hg (1 mm Hg = 0.133 kPa)
      and saturation of pulse oximeter (SpO(2)) was from 85% to 88% with oxygen 5 L/min
      by nasal cannula. His chest CT, bronchoscopy with bronchoalveolar lavage and
      transbronchial biopsies were consistent with PAP. Whole-lung lavage was performed
      in the operation room under general anesthesia. A double-lumen tube was intubated
      in order to selectively ventilate and lavage a single lung independently. During
      mechanical ventilation for both lungs, the SpO(2) was from 80% to 90%, but when a
      single right lung ventilation was tried, the SpO(2) (from 68% to 80%) dropped
      significantly. To ensure adequate oxygen supply during lavage, a veno-arterial
      ECMO was set up by inserting catheters percutaneously into the right femoral
      artery and right femoral vein respectively. Then the SpO(2) improved, from 89% to
      97% during single right lung ventilation. The left lung was lavaged with a total
      of 20.8 L of normal saline. The SpO(2) ranged from 80% to 94% during the lavage.
      After the lavage, the patient no longer experienced shortness of breath. Then 28
      days later the right lung was lavaged without the aid of ECMO. A month after the
      second lavage, his chest CT showed marked improvement in infiltrates of both
      lungs. CONCLUSION: When a patient with PAP has refractory hypoxemia prior to the
      lavage procedure, ECMO should be considered in order to avoid severe hypoxaemia
      with fatal consequences during lavage.

PMID- 15854434
TI  - [Comparison of four methods in the detection of isoniazid resistance in clinical
      isolates of Mycobacterium tuberculosis].
AB  - OBJECTIVE: To evaluate the use of phage amplified biologically (PhaB) assay,
      Bactec-960 system, minimum inhibitory concentration (MIC) method and gene chip in
      drug susceptibility testing of isoniazid (INH) in clinical isolates of
      Mycobacterium tuberculosis (MTB). METHODS: INH resistance of 167 clinical
      isolates of MTB was detected by PhaB assay, Bactec-960 system, MIC and gene-chip
      methods respectively, and the results of these four methods were compared.
      RESULTS: 111 INH resistant isolates and 56 INH sensitive isolates were detected
      by Bactec-960 system. If the result of Bactec-960 system was set as the golden
      standard, the sensitivity, specificity, positive predictive value (PPV), negative
      predictive value (NPV), and accuracy of PhaB assay were 96.4%, 96.4%, 93.1%,
      98.2%, and 96.4% respectively; the sensitivity, specificity, PPV, NPV, and
      accuracy were 92.9%, 99.1%, 98.1%, 96.5%, and 97.0% for the MIC method, and they
      were 83.9%, 96.4%, 92.2%, 92.2%, and 92.2% respectively for the gene-chip method.
      If the result of the MIC method was set as the golden standard, the sensitivity,
      specificity, PPV, NPV, and accuracy of PhaB assay were 100%, 95.6%, 91.4%, 100%,
      and 97.0% respectively. The sensitivity, specificity, PPV, NPV, and accuracy were
      98.1%, 96.5%, 92.9%, 99.1%, and 97.0% for the Bactec-960 system, and they were
      88.7%, 96.5%, 92.2%, 94.8%, and 94.0% respectively for the gene-chip method.
      CONCLUSIONS: The PhaB assay is highly sensitive and specific, and its result is
      highly consistent with those of the Bactec-960 system and the MIC method. It is
      easy to use and took only three days in the detection of drug susceptibility of
      INH in clinical isolates of MTB. The results indicate that this low-cost assay
      can be used in rapid screening for INH resistance in MTB isolates. The MIC method
      proves to be as efficient as the Bactec-960 system, but whether it can be used as
      the standard method still needs further investigation. The sensitivity of the
      gene-chip method is lower as compared to the other methods, and therefore can
      only be used as an ancillary test.

PMID- 15854436
TI  - [Characterization of the katG, inhA, ahpC, kasA, and oxyR gene mutations in
      isoniazid-resistant and susceptible strain of Mycobacterium tuberculosis by
      automated DNA sequencing].
AB  - OBJECTIVE: To study the characteristics of katG, inhA, ahpC, kasA, and oxyR gene
      mutations in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis.
      METHODS: A total of 101 isoniazid-resistant and 43 susceptible strains of
      Mycobacterium tuberculosis were analyzed by PCR and sequence analysis of their
      katG, inhA, ahpC, kasA, and oxyR genes. RESULTS: (1) Sequencing of katG from 101
      INH-resistant strains showed point mutations, small deletions or insertions in 81
      isolates (80.2%), but no complete deletions were identified. The mutations at 16
      position were found for the first time. Point mutations at position 315 were
      found in the genomes of 38.6% (39/101) of isoniazid-resistant strains. Low level
      isoniazid resistant strains (1 microg/ml) had higher mutation frequency at 315
      Ser than high level isoniazid resistant strains (10 microg/ml; chi(2) = 9.31, P <
      0.05). Mutations at position 463 were detected in 58 (57.4%) isoniazid-resistant
      strains. Arg463leu was also present in 23 of 43 susceptible strains. (2)
      Mutations in inhA genes were identified in 5 isoniazid-resistant isolates (4.9%).
      None of the susceptible strains contained any mutation in inhA genes. (3) Only 3
      isolates in the 101 (2.97%) isoniazid-resistant clinical isolates had mutations
      in ahpC genes. No mutations were identified in the ahpC genes in 43 isoniazid
      susceptible isolates. (4) Mutations in kasA genes were present in 17 of 101
      (16.8%) isoniazid-resistant isolates. However, G312S was also present in 3 of 43
      susceptible strains. (5) None of the isoniazid-resistant strains and susceptible
      isolates contained oxyR gene mutation. (6) Taken together, 91 of 101 (90%)
      isoniazid-resistant strains had mutations in katG, inhA, ahpC, and kasA genes
      which were associated with drug resistance. CONCLUSION: These studies provide
      further evidence supporting the association between katG, inhA, ahpC, and kasA
      gene mutations and INH resistance in Mycobacterium tuberculosis, while other
      mechanisms of INH resistant may exist.

PMID- 15854437
TI  - [Screening and construction of recombinant BCG strains expressing the Ag85B-ESAT6
      fusion protein].
AB  - OBJECTIVE: To screen and construct recombinant BCG strains which express the
      Ag85B-ESAT6 fusion protein. METHODS: The heat shock protein 60 (Hsp60) and the
      alpha-ss signal peptide encoding sequence were amplified by PCR from
      Mycobacterium tuberculosis H(37)Rv and cloned into E. coli/Mycobacteria shuttle
      vector-pOLYG. The resulting expression vector was named pDE22, and then ag85b and
      esat6 genes were cloned into pDE22 at different sites. The resulting recombinant
      plasmids Ag85B-ESAT6 and ESAT6-Ag85 were electroporated into BCG. Positive clones
      were screened by hygromycin resistance and confirmed by PCR. Recombinant BCG
      culture supernatants were collected and analyzed by SDS-PAGE and Western blot.
      RESULTS: Two recombinant BCG strains were obtained, which secreted the 37,000
      fusion protein in their culture supernatant, which was confirmed by Western blot
      with specific immune serum against Ag85B and ESAT6. CONCLUSIONS: Recombinant BCG
      strains expressing Ag85B and ESAT6 fusion proteins of Mycobacterium tuberculosis
      were constructed. They may serve as new vaccine candidates for preventing
      tuberculosis.

PMID- 15854438
TI  - [Study on the drug resistance and beta-lactamases of Pseudomonas aeruginosa].
AB  - OBJECTIVE: To analyze the resistance and beta-lactamases of 93 strains of
      Pseudomonas aeruginosa. METHODS: Antimicrobial activity to 93 strains of
      Pseudomonas aeruginosa were determined by K-B test, and the beta-lactamases
      produced by these strains were characterized by isoelectric focusing, three
      dimensional test, 2-mercaptopropanoic acid inhibited assays, and polymerase chain
      reaction (PCR). RESULTS: The resistance of amikacin, cefepime,
      cefoperazone/sulbactam, ceftazidime, meropenem were 82.8%, 81.7%, 81.7%, 80.6%,
      77.4%, respectively. The susceptibility of rate imipenem was 71.0%. Three
      dimensional test showed that 14 strains produced carbapenemases, only and 2
      strain produced metallo-beta-lactamase, which was in agreement with the result of
      2-mercaptopropanoic acid inhibited assays, 13 strains produced AmpC enzymes, and
      2 strains produced AmpC enzymes and ESBLs. The 15 strains and other two (Number
      19, 54) had 1 band on IEF electrophoresis, and the isoelectric points were 9.0
      and 6.3 respectively. The 2 metallo-beta-lactamases were revealed by amplified
      PCR products with VIM-2 specific PCR, the production was sequenced and revealed
      that the found to match with the known sequences of VIM-2. CONCLUSION: The
      production of carbapenemases and AmpC enzymes was the main cause for multi-drug
      resistance in Pseudomonas aeruginosa in our hospital.

PMID- 15854440
TI  - [Effects of adenoviral vector containing human angiotensin II type 1 receptor
      antisense cDNA on biological action of human pulmonary artery smooth muscle
      cells].
AB  - OBJECTIVE: To investigate the effect of human angiotensin II (AngII) type 1
      receptor (AT(1)R) antisense cDNA (ahAT(1)) on migration, proliferation, and
      apoptosis of cultured human pulmonary artery smooth muscle cells (PASMC).
      METHODS: Two recombinant adenoviral vectors, AdCMVahAT(1) containing full length
      antisense cDNA targeting to human AT(1)R mRNA, and AdCMVLacZ containing LacZ,
      were constructed by orientation clone technology and homologous recombination.
      The PASMC was divided into 3 groups (DMEM, AdCMVLacZ, AdCMVahAT(1)) and different
      interventions were given to different groups. AT(1)R expression was detected by
      RT-PCR and immunohistochemistry method; migration of PASMC was measured by
      Boyden's Chamer method. Other PASMC was divided into 4 groups (DMEM, AngII,
      AdCMVLacZ + AngII and AdCMVahAT(1) + AngII), and only the last 2 groups were
      respectively transfected with AdCMVLacZ and AdCMVahAT(1) before administration of
      AngII. From 6 h to 96 h after stimulation by AngII (10(-7) mol/L), proliferation
      index (PI) and apoptosis of PASMC were determined by flow cytometry. RESULTS: At
      the 48 h the level of AT(1)R mRNA was significantly less in PASMC transfected
      AdCMVahAT(1) than that in group DMEM and in group AdCMVLacZ. The protein level
      showed a same difference (P < 0.01). At 24 h the migration distance of PASMC also
      was significantly less in group AdCMVahAT(1) than that in group DMEM and Group
      AdCMVLacZ (P < 0.01). Stimulated by AngII for 48 h, in group AngII the PI of
      PASMC markedly increased (P < 0.01 vs group DMEM). But in Group AdCMVahAT(1) +
      AngII PI of PASMC clearly decreased (P < 0.01 vs group AngII and group DMEM
      respectively). There was no statistic difference of PI between group AdCMVLacZ +
      AngII and group AngII. Moreover, apoptosis peak emerged only in group
      AdCMVahAT(1) + AngII. The rate of apoptosis in those PASMC used AdCMVahAT(1) and
      AngII was 24.70 +/- 4.04 (P < 0.01 vs the other 3 groups respectively).
      CONCLUSIONS: These results indicate that AngII stimulates proliferation via AT(1)
      receptors in human PASMC, and antisense cDNA targeting to human AT(1)R
      transfection mediated by adenoviral vector has powerful inhibitory effects on
      AngII-induced migration and proliferation of human PASMC by attenuating AT(1)R
      mRNA and protein expression. Also, it can promote apoptosis of human PASMC. That
      demonstrate that AT(1)R antisense cDNA is a potent inhibitors of the actions of
      AngII on PASMC. Antisense inhibition targeting to AT(1)R has therapeutic
      potential for the treatment of pulmonary vascular diseases.

PMID- 15854451
TI  - [Murine models of asthma].

PMID- 15854450
TI  - [Proteomics in the pathogenetic study of lung cancer].

PMID- 15854453
TI  - [Laparoscopic surgery in the treatment of abdominal diseases: present status and
      prospects].

PMID- 15854455
TI  - [Mastoscopic surgery the progress and problems].

PMID- 15854454
TI  - [Minimally invasive surgery and problems in gynecologic practice of China].

PMID- 15854456
TI  - [Laparoscopic cholecystectomy with remote zeus surgical robotic system: report of
      16 cases].
AB  - OBJECTIVE: To explore the methodology and operative essentials of laparoscopic
      cholecystectomy with remote Zeus surgical robotic system. METHODS: Based on
      strict training and successful experiment in animal model of swine, laparoscopic
      cholecystectomy using Zeus robotic system was performed on 16 patients with
      biliary diseases, including choledocholithiasis, cholelithiasis, polyposis of
      gallbladder, and chronic cholecystitis, 10 males and 16 females, aged 33 (14
      approximately 27), 26 April to 31 August 2004. The general data, preoperative
      preparation time, operation time, amount of bleeding, complications, and
      hospitalization time were analyzed. RESULTS: All operations were performed
      without event. Along with the accumulation of experience the preoperative
      preparation time was shortened from 90 min to 30 min with an average of 41.7 min,
      and the operation time from 120 min to 30 min with an average of 64.4 min. The
      average amount of bleeding was 27.7 ml, and the average postoperative
      hospitalization time was 2.4 d. A telephone follow-up 30 days after operation
      showed no abnormality. CONCLUSION: Laparoscopic cholecystectomy with Zeus
      surgical robotic system is feasible and reliable with the advantages of clearer
      images in the field of operation, more precise handling, and remote surgery or
      education.

PMID- 15854457
TI  - [The anatomical characteristics and its applied significance of laparoscopic
      rectal surgery].
AB  - OBJECTIVE: To realize the anatomical characteristics of laparoscopic rectum
      surgery and its clinical significance. METHODS: 117 cases with benign and
      malignant diseases of rectum were operated by laparoscopic methods. The anatomy
      closely related with operation was analyzed. RESULTS: The median operative time
      were 144 min. 4 cases were converted to open operations, so the converted rate
      was 1.7%. The blood loss in operation was rather little with an average of 126
      ml. No instant or delayed injury of ureters, large bleeding in front of sacrum
      and other operation-related severe complications happened intra- and after
      operation. Dissecting only in one case disrupted the anterior-left wall of
      rectum. CONCLUSION: Laparoscopic rectal surgery is clinically feasible. Mastering
      the anatomical characteristics of laparoscopic rectum surgery can make us reduce
      the operative mistakes and complications.

PMID- 15854458
TI  - [Laparoscopic hepatectomy by curettage and aspiration: 54 cases reported].
AB  - OBJECTIVE: Introduce the experience on 54 cases of laparoscopic hepatectomy-liver
      transection by curettage and aspiration (LTCA). METHODS: We used Peng
      multifunctional operative dissector (PMOD) to perform laparoscopic liver
      transection by curettage and aspiration. RESULTS: 52 patients underwent
      laparoscopic hepatectomy successfully. 2 patients were converted to an open
      hepatectomy for raw surface hemorrhage or severe abdominal cavity adherence. Mean
      operative time was 146.5 minutes, the mean bleeding volume was 460 mL, the
      largest excised liver size was 20 cm x 7 cm x 4 cm. Bile leakage and pneumothorax
      occurred in 2 patients. Patients could walk one day after operation and were
      discharged one week postoperatively. CONCLUSION: Laparoscopic hepatectomy by
      curettage and aspiration is a safe and effective technique. PMOD is an optimal
      tool to perform laparoscopic hepatectomy.

PMID- 15854459
TI  - [Laparoscopic resection of true pancreatic cyst: report of 5 cases].
AB  - OBJECTIVE: To summarize the experience in laparoscopic resection of true
      pancreatic cyst. METHODS: Five patients with true pancreatic cyst, including 1
      case of pancreatic head cyst and 4 cases of distal pancreatic cyst, underwent
      laparoscopic resection. Among them one case with pancreatic head cyst and 4 cases
      of distal pancreatic cyst underwent simple laparoscopic cyst resection and one
      case of distal pancreatic cyst underwent laparoscopic distal pancreatectomy with
      resection of the spleen. The curative effects were evaluated. A follow-up lasting
      2 approximately 33 months was conducted. RESULTS: All operations were successful
      with intraoperative blood loss of 50 to 150 ml. The patients could get up and
      move about 6 hours after the operation and were recovered and discharged 4 to 6
      days later. Follow-up showed that all symptoms disappeared and no recurrence of
      cyst occurred. CONCLUSION: Laparoscopic resection of true pancreatic cyst is
      feasible with the advantages of reduced injury and earlier recovery.

PMID- 15854460
TI  - [Hand-assisted laparoscopic renal surgery: report of 45 cases].
AB  - OBJECTIVE: To evaluate the effect and clinical application of hand-assisted
      laparoscopic renal surgery. METHODS: Forty-five patients with urologic diseases
      underwent hand-assisted laparoscopic renal surgery: radical nephrectomy was
      performed on 23 cases, simple nephrectomy on 9 cases, nephroureterectomy on 8
      cases, excision of cysts of kidney on 3 cases, partial nephrectomy on 1 case, and
      upper pole heminephrectomy in duplex kidney on 1 case. The operation was
      performed by transperitoneal approach in 38 cases and by underwent and by
      retroperitoneal approach in 7 cases. RESULTS: Hand-assisted laparoscopic renal
      surgery were performed successfully on all patients. The mean operation time was
      154.7 minutes (40 approximately 300 min), and the mean estimated blood loss was
      100.4 ml (15 approximately 300 ml). CONCLUSION: With the advantages of minimal
      invasion, less blood loss, faster recovery, hand-assisted laparoscopic renal
      surgery is worth popularizing in urologic clinical practice.

PMID- 15854461
TI  - [Evaluation of laparoscopic surgery in the early stage-malignant tumor of ovary
      with lower risk].
AB  - OBJECTIVE: To evaluate the laparoscopic operation for early ovarian malignant
      tumor with low risk. METHODS: Ten patients with ovarian malignant tumor who
      underwent laparoscopic total hysterectomy, pelvic lymph nodes dissection,
      bilateral adnexectomy, ovarian aortic and vein high ligation, omentectomy, and
      additional appendectomy. Eleven patients with the same diagnosis who underwent
      operation by laparotomy were served as control group. The operation time,
      intraoperative blood loss, number of pelvic lymph nodes excised, and
      postoperative recovery were analyzed retrospectively. RESULTS: Frozen section
      method during operation proved the diagnosis of ovarian malignant tumor and
      cytological examination proved a negative result of the peritoneal irrigation
      liquid. The operation time was 298 min +/- 60 min for the laparoscopy group and
      182 min +/- 43 min for the laparotomy group (P < 0.05). The intraoperative blood
      loss was 280 ml +/- 156 ml for the laparoscopy group and 346 ml +/- 170 ml for
      the laparotomy group (P < 0.05). The number of pelvic lymph node resected was 25
      +/- 5 and 27 +/- 7 for the laparoscopy group and laparotomy group respectively (P
      > 0.05). The postoperative illness rate was 20.0% and 72.7% for the laparoscopy
      group and laparotomy group respectively (P < 0.01). Seven patients and 1 case in
      the laparoscopy group and laparotomy group left their beds 48 hours after
      operation (P < 0.05). The right obtuator nerve was injured and was sutured on 1
      patient in the laparoscopy group. CONCLUSION: The whole procedure of total
      hysterectomy, bilateral adnexectomy, pelvic lymph node dissection, ovarian aortic
      and vein high ligation, omentectomy, and additional appendectomy may be performed
      under laparoscope in the treatment of early stage ovarian malignant tumor with
      lower risk. The laparoscopic operation has the advantage of less intraoperative
      bleeding, less morbidity and rapid recovery.

PMID- 15854462
TI  - [Transcervical resection of myoma in treatment of hysteromyoma, experience in 962
      x?cases].
AB  - OBJECTIVE: To study the technique and effect of transcervical resection of myoma
      (TCRM) in treatment of hysteromyoma. METHODS: 962 women suffering type 0
      hysteromyoma (n = 281), 316 type 1 hysteromyoma (n = 316), type 2 hysteromyoma (n
      = 282), submucous and intramural myoma (n = 34), cervical myoma (n = 11),
      prolapse myoma (n = 23), and adenomyoma (n = 15) underwent TCRM with "five-step
      technique", monitored by B-ultrasound or laparoscopy, Follow-up lasted more than
      6 months. RESULTS: The primary operation successful rate was 99.77%. The mean
      size and depth of uterus were 7.44 +/- 1.3 gestation weeks and (8.31 +/- 1.43)
      cm, the diameter of the biggest myoma was 7.2 cm. The mean weight of the resected
      tissues was (22.63 +/- 31.41) g, and the mean operation time and blood loss
      during the operation were 32.50 +/- 172.72 minutes and (7.75 +/- 19.49) ml. No
      transfusion was needed. The complications included postoperative fever (3 cases),
      uterine bleeding (1 case), uterine perforation (1 case), and TURP syndrome (2
      cases). Postoperative scanty menstrual rate was 100% in the type 0 hysteromyoma
      group, 99.1% in the type I hysteromyoma group, 94.02% in the type II hysteromyoma
      group, 100% in the cervical myoma and prolapse myoma group, 84% in the multiple
      myoma and intramural myoma group, and 87% in the adenomyoma group respectively.
      The alleviation rates of dysmenorrhea and anemia were 78% and 82.95%
      respectively. Those who have severe complications of internal medicine showed
      obvious improvement. The residual myoma of 2 cases were resected during the
      secondary operation 9 days and 3 months after the primary operation. 455 cases
      (52.17%) resumed their work in 1 month postoperatively. 32 living infants were
      delivered. CONCLUSION: Safe and highly effective, TCRM can be the first choice in
      treatment of submucous and intramural hysteromyoma.

PMID- 15854463
TI  - [Effect of enucleation of hysteromyoma by laparoscopic surgery on protein
      oxidation and lipid hyperoxidation].
AB  - OBJECTIVE: To evaluate the effect of laparoscopic surgery on and lipid
      hyperoxidation in patients with hysteromyoma. METHODS: Forty patients with
      hysteromyoma were randomly divided into 2 equal groups: laparoscopy group and
      laparotomy group. The plasma advanced oxidation protein products (AOPP),
      malondialdehyde (MDA), antioxidant activity (AOA), and glutathione peroxidase
      (GPx) activity were measured before operation, just after operation (5 minutes
      after deflation) and 24 hours after operation. RESULTS: (1) In the laparoscopy
      group, the levels of AOPP and MDA were (50.20 +/- 9.23) micromol/L and (1.85 +/-
      0.19) micromol/L before operation, increased significantly just after operation
      [(68.75 +/- 12.69) micromol/L and (2.52 +/- 0.55) micromol/L respectively, both P
      < 0.01], and recovered to the normal level 24 hour postoperatively [(49.70 +/-
      9.92) micromol/L and (2.05 +/- 0.68) micromol/L respectively, both P > 0.05]. The
      levels of GPx and AOA decreased significantly just after operation [(0.29 +/-
      0.09) U/ml vs. (0.62 +/- 0.27) U/mL and (0.90 +/- 0.24) mmol/L vs. (1.41 +/-
      0.39) mmol/L respectively, both P < 0.01], and the GPx level recovered 24 hours
      after operation [(0.52 +/- 0.06) U/mL, P > 0.05], however, the AOA level was
      still lower [(1.00 +/- 0.31) mmol/L, P < 0.01]. In the laparotomy group, the
      levels of plasma AOPP and MDA level slightly increased just after operation in
      comparison with those before operation [(53.39 +/- 9.86) micromol/L vs. (52.30 +/
      7.10) micromol/L and (2.09 +/- 0.51) micromol/L vs. (1.83 +/- 0.64) micromol/L
      respectively, both P > 0.05] and continued to increase 24 hours after operation
      [(63.40 +/- 15.5) micromol/L, P < 0.05, and (2.42 +/- 0.44) micromol/L, P <
      0.01]; the GPx and AOA levels decreased a little just after operation [(0.51 +/-
      0.17) U/mL vs. (0.57 +/- 0.21) U/mL and (1.20 +/- 0.46) mmol/L vs. (1.33 +/-
      0.37) mmol/L, both P > 0.05] and continued to decrease 24 hours after operation
      [(0.35 +/- 0.19) U/mL and (0.92 +/- 0.22) mmol/L respectively, both P < 0.01].
      Compared with those of the laparotomy group, the plasma AOPP and MDA levels of
      the laparoscopy group were both significantly lower (P < 0.01 and P < 0.05), and
      the GPx level was significantly higher (P < 0.01) 24 hours after operation,
      however, the AOA level was not significantly different (P > 0.05). CONCLUSION:
      Laparoscopic surgery is better than laparotomy. Protein oxidation and lipid
      hyperoxidation occur during the laparoscopic surgery, however, disappeared after
      operation. Free radicals are generated by the end of laparoscopic procedure,
      possibly as a result of an ischemia-reperfusion phenomenon induced by the
      inflation and deflation of the pneumoperitoneum. AOPP and MDA are induced during
      laparoscopic procedure and then return to the normal levels finally.

PMID- 15854464
TI  - [Application of endoscopy-assistant operation in surgical treatment of breast
      diseases].
AB  - OBJECTIVE: To explore the technique and problems of endoscope-assistant breast
      surgery. METHODS: Five patients with breast cancer underwent endoscope-assistant
      modified radical mastectomy, 30 patients with breast cancer underwent endoscope
      assistant modified radical mastectomy with small incision, and 13 patients with
      breast cancer underwent endoscope-assistant resection of breast cancer with
      retained breast plus axillary lymph node dissection. Two patients with
      fibroadenoma and 2 patients with fibrocystic disease breast with atypical
      hyperplasia were treated with endoscope-assistant subcutaneous total mastectomy
      and breast reconstruction by one-stage silica gel filling operation. Seven
      patients with fibrocystic disease with atypical hyperplasia and 16 patients with
      gynecomastia were treated with endoscope-assistant subcutaneous total mastectomy.
      One 10-month-old infant with huge chest lymphangioma was treated with endoscope
      assistant tumor resection via axilla. RESULTS: All operations were performed
      smoothly. The duration of operation was 180 approximately 360 min. The frozen
      sections of skin and breast tissue at the incision margin resected during
      operation endoscope-assistant modified radical mastectomy with small incision and
      endoscope-assistant conservative surgery were all negative There were 2 cases of
      postoperative incisional bleeding, 1 case of skin margin necrosis of axillary
      incision, 1 case of skin margin incisional necrosis after endoscope-assistant
      resection of breast cancer with retained breast plus axillary lymph node
      dissection, 4 cases of epidermal necrosis of nipple, and one case of full
      thickness skin necrosis of nipple surface. CONCLUSION: Endoscope-assistant breast
      surgery has changed the routine method in breast operation and manifests the
      cosmetic effects that cannot be achieved by routine surgery.

PMID- 15854465
TI  - [Two year follow-up of acute ischemic syndrome without ST elevation].
AB  - OBJECTIVE: To analyze the characteristics, treatment, and natural course during
      two years of the patients with acute coronary ischemic syndrome (ACS) without ST
      elevation in China as a part of the international multicentre registry of acute
      ischemic syndrome, Organization to Assess Strategies for Ischemic Syndromes
      (OASIS). METHODS: 2294 patients with ACS without ST elevation, including unstable
      angina pectoris and non-Q-wave myocardial infarction, aged 63 +/- 8, 62.3% being
      males, were registered and observed for 2 years based on informed consent in the
      northwest, north, and northeast China. The specific clinical protocols for
      patients were decided by the attending physicians without outside intervention.
      The patients' clinical characteristics, treatments, major events in hospital, and
      natural course of disease during the period of two years were recorded by filling
      in Case Report Forms offered by Canadian Cardiovascular Collaboration. RESULTS:
      89.8% of the patients showed abnormal ECG. The most probable clinical diagnosis
      on admission was unstable angina in 88.5% of the patients and non-Q-wave
      myocardial infarction in the other 11.5%. 56.2% of the patients had past history
      of coronary artery disease, and nearly half of them had myocardial infarction.
      57.4%, 18.3%, 47.6%, and 7.1% of them had the prior history of hypertension,
      diabetes, cigarette smoking and stroke respectively. During hospitalization, anti
      platelet therapy and nitrate were used in 94.5% and 96.6% of the cases
      respectively, and 67.5%, 57.4%, and 59.1%t of them took beta-blockers, calcium
      antagonists and angiotensin-converting enzyme inhibitor (ACEI) respectively
      simultaneously. The medication rate dropped by 20.2% approximately 50.2% after
      discharge from hospital. During the two-year follow up the therapeutic rates of
      anti-platelets, nitrates, beta-blockers, calcium antagonists, and ACEI were
      73.8%, 69.4%, 43.9%, 35.8%, and 31.6% respectively. During the 2 years 43.1%,
      23.1%, and 8.2% of the patients underwent coronary angiography, percutaneous
      coronary intervention (PCI), and coronary artery bypass graft surgery (CABG)
      respectively. The two-year total mortality was 8.0%. The most common causes of
      death were severe arrhythmias or sudden death with an incidence of 4.3%. The
      major events were refractory angina, heart failure, new MI, stroke, and major
      bleeding with incidence rates of 29.4%, 15.4%, 7.9%, 4.8%, and 0.3%,
      respectively. CONCLUSION: Most patients with acute ischemic syndrome without ST
      elevation in China are diagnosed as unstable angina. The patients with acute
      ischemic syndrome are diagnosed as unstable angina mostly in China. More than
      half of the patients are treated with anti-platelets, nitrates, beta-blockers,
      calcium antagonists, and ACEI during hospitalization. The medication rate
      gradually decreases after discharge. The two-year mortality is 8.0%. The most
      common causes of death include severe arrhythmias and sudden death.

PMID- 15854466
TI  - [Using ANN and serum protein pattern models in liver cancer diagnosis].
AB  - OBJECTIVE: To set up a method for the detection of the serum protein fingerprint
      pattern by using the protein chip technology for exploration of serum protein
      fingerprint pattern models based on the artificial neural network in diagnosis of
      liver cancer. METHODS: One hundred and six serum samples form subjects with liver
      cancer, hepatocirrhosis, and healthy individuals were detected with protein
      biochip surface enhanced laser desorption/ionization time-of-flight mass
      spectrometry (SELDI-TOF-MS) for protein fingerprint pattern, and analyzed with
      the artificial neural network. The 106 samples were randomly put into a training
      group (n = 70, 35 patients with liver cancer, 14 patients with hepatocirrhosis,
      and 21 healthy individuals) and a blind test group (n = 36, 17 patients with
      liver cancer, 8 patients with hepatocirrhosis, and 11 healthy individuals).
      RESULTS: The serum protein fingerprint pattern model obtained by the artificial
      neural network from training group was used to detect the 36 unknown serum
      samples. The sensitivity and specificity of this method in detection of liver
      cancer were 88.2% (15/17) and 94.6% (18/19) respectively. CONCLUSION: In
      comparison with the traditional methods, this new method has higher sensitivity
      and specificity in diagnosis of liver cancer and should be further studied.

PMID- 15854467
TI  - [Vaccination of mice with recombinant nucleic acid vaccine encoding the integral
      membrane protein Sj23 and cytokine IL-12 elicits specific immune responses
      against schistosoma japonica].
AB  - OBJECTIVE: To develop a Schistosoma japonica integral membrane protein Sm23 or
      Sj23 combined with murine IL-12 DNA-base vaccine against schistosomiasis.
      METHODS: Plasmids pVIVO2-Sj23 and pVIVO2-IL12-Sj23, expressing the integral
      membrane protein Sj23 of Schistosoma japonica and/or murine IL-12 were
      constructed. The plasmid pVIVO2-IL12-Sj23 was transfected into the human
      embryonic kidney cells of the line 293. RT-PCR was used to detect the expression
      of Sj23 mRNA in the 293 cells. Indirect immunofluorescence test was used to
      detect the expression of Sj23 protein. Fifty BALB/c mice were randomly divided
      into 5 equal groups to be injected with pVIVO2-IL12-Sj23 plasmid DNA, pVIVO2-Sj23
      plasmid DNA, pVIVO2-IL12 plasmid DNA, pVIVO2 blank vector, and normal saline
      respectively into the quadriceps muscle of thigh. Four weeks after each mouse
      were infested with 40 +/- 2 cercariae of Schistosoma japonica. Six weeks after
      the infestation the mice were killed to calculate the load of schistosoma and the
      amount of eggs per gram (EPG) of liver so as to calculate the worm reduction rate
      and egg reduction rate after the vaccination. Before immunization, 4 weeks after
      immunization, and 6 weeks after immunization blood samples were collected from
      the caudal veins of mice. With soluble egg antigen (SEA) and adult worm antigen
      (AWA) ELISA was used to detect the serum IgG level. Western blotting was used to
      detect the serum specific anti-Sj23 IgG level. Six weeks after the cercaria
      challenge single splenocyte suspension was prepared. Splenocytes were cultured
      with SEA, and concanavalin A (ConA). ELISA was used to detect the levels of IL-4
      and IFN-gamma in the supernatant. Flow cytometry was used to analyze the
      subgroups of splenocyte. RESULTS: + Forty-eight hours after the transfection, RT
      PCR and indirect immunofluorescence test showed expression of Sj23 mRNA and
      protein in the HEK-293 cells. The worm reduction rate was 45.53% and the egg
      reduction was 58.35% in the pVIVO2-IL12-Sj23 group, significantly higher than
      those in the monovalent vaccine pVIVO2-Sj23 group (27.23% and 33.93%
      respectively, both P <0.05). ELISA and Western blotting analysis showed that the
      level of IgG specific for Sj23 significantly increased 4 weeks after vaccination
      in the pVIVO2-IL12-Sj23 and pVIVO2-Sj23 groups without significant difference
      between these 2 groups (P > 0.05). After stimulation of ConA and SEA the level of
      Th1 type cell factor IFN-gamma was higher and the level of the Th2 type cellular
      factor IL-4 was low in the supernatant of suspension of splenocytes of the pVIVO2
      IL12-Sj23 group. FCM showed the percentages of CD4+ and CD8+ subgroups of the
      murine splenocytes of all experimental groups were all significantly lower than
      those of the normal mice (all P < 0.001 approximately 0.02). However, there was
      no significant difference in the CD4+/CD8+ ratio among the experimental groups
      (all CONCLUSION: pVIVO2-IL12-Sj23 is sufficient to elicit significant levels of
      protective immunity against Schistosoma japonica challenge infection. IL-12, a
      cytokine and a gene adjuvant, is able to induce Th1 responses and hence the
      protective immunity.

PMID- 15854468
TI  - [Effect of specific siRNA targeting against bcr-abl chimeric gene on chronic
      myelogenous leukemia cells].
AB  - OBJECTIVE: To investigate the effect of specific small interfering RNA (siRNA)
      targeting against bcr-abl chimeric gene on the biological traits of chronic
      myelogenous leukemia (CML) cells. METHODS: CML cells of the line K561
      transcribing a type of b3: a2 mRNA of bcr-abl chimeric gene were cultured. A 21nt
      siRNA targeting against the chimeric location of the b3: a2 mRNA of bcr-abl
      chimeric gene was designed, synthesized, and transfected into the K562 cells as
      RNA interference group. Another K562 cells were transfected with fluorescein
      enzyme gene specific siRNA as indifferent controls, or with lipid alone as blank
      vector controls. Some K562 cells without treatment were used as normal controls.
      48 hours after the transfection Western blotting was used to detect the
      expression of P210bcr-abl fusion protein. 3H-TdR incorporation was used to detect
      the proliferation activity of K562. Annexin V-fluorescencein isothiocyanate
      (FITC)/phosphatidylinositol (PI) staining was used to detect the apoptosis of
      K2562 cells. Flow cytometry was used to observe the cell cycle of K562 cells.
      Benzidine staining was used to detect the differentiation of K562 cells towards
      erythrocytic series. Western blotting was used further to detect the expression
      of apoptosis-related protein Bcl-xL/Bax. RESULTS: (1) In contrast with the
      control groups, the expression level of bcr-abl chimeric gene was much lower in
      the RNAi group. (2) (3)H-TdR incorporation test showed time-dependent inhibition
      of proliferation of K562 cells, reflected in decrease of counts per minute (CPM)
      value in RNAi group 24 h, 48 h, 72 h, and 96 h after siRNA transfection by
      33.06%, 52.25%, 57.64%, and 70.87% respectively (F=17.7, P < 0.01). (3) About
      43.2% of K562 cells in the RNAi group were apoptotic 48 h after siRNA
      transfection (F=13.6, P < 0.01). (4) In contrast with the control groups, the
      expression of apoptosis-associated protein Bcl-xL was greatly down-regulated;
      however, the expression of Bax protein showed little change. (5) The percentage
      of benzidine-positive cells in the RNAi group was 23.5% +/- 3.2%, significantly
      higher than those in the indifferent control group, blank vector group, and
      normal control group (2.4% +/- 0.3%, 4.5% +/- 0.5%, and 3.6% +/- 0.2%
      respectively, all P < 0.01), which meant that part of the K562 cells
      differentiated towards erythrocytic series. (6) The percentage of G1 phase of
      K561 cells in the RNA1 group was significantly higher than those of the other
      groups (F = 6.2, P < 0.05), showing a capture in G1-phase of cell cycle.
      CONCLUSION: The specific siRNA distinctly inhibits the expression of bcr-abl
      chimeric gene and influences essential biological traits of K562 cells, which
      will ultimately result in differentiation or apoptosis of K562 cells.

PMID- 15854469
TI  - [Changes of growth hormone and insulin-like growth factor axis in patients with
      anorexia nervosa and its clinical significance].

PMID- 15854470
TI  - [Effect of tortoise plastron on cell differential of neurons after mesenchymal
      stem cell transplantation in cerebral ischemia in rats].

PMID- 15854471
TI  - [Revascularization of multiple coronary vascular disease in diabetes mellitus--a
      case report].

PMID- 15854472
TI  - [Huge malignant gastrointestinal stromal tumor--a case report].

PMID- 15854473
TI  - [Progress on the study of mechanism and biomarkers of arterial and cardiac
      aging].

PMID- 15854474
TI  - [Amplatzer septal occluder interventional therapy of acute myocardial infarction
      complicated with ventricular septal perforation--report of 2 cases].

PMID- 15854475
TI  - [Advance in minimally invasive neurosurgery].

PMID- 15854476
TI  - [The importance of solving the clinical dilemma by ethic principles].

PMID- 15854477
TI  - [Microsurgical treatment of posterior cranial fossa tumors via keyhole
      approaches].
AB  - OBJECTIVE: To explore the surgical outcome and skills of keyhole approaches to
      posterior cranial fossa tumors. METHODS: A retrospective analysis of the clinical
      data of 43 consecutive patients with posterior cranial fossa tumors, including
      acoustic neurinoma, petroclival meningioma, pons tumor, fourth ventricular tumor,
      etc. was conducted. Subtemporal, retromastoid, or middle suboccipital keyhole
      approach was chosen respectively according to the anatomic positions of those
      different tumors. The length of the incision was about 4 cm, and the diameter of
      bone window was 2.0 - 2.5 cm. Normally dura was sutured tightly and no catheter
      was placed in the surgical fields. RESULTS: The tumors were totally removed in 37
      of the 43 patients (86.0%), subtotally removed in 5 (11.6%) and mostly removed in
      1 (2.3%). There were no complications obviously related to the limited exposure
      resulting from keyhole approaches. All of the 18 acoustic neurinomas (100%) were
      totally removed and the facial nerves of 15 patients (83.3%) were preserved
      anatomically, however, one patient died of brain stem edema on the 2nd
      postoperative day. Out of the 8 petroclival meningiomas, 5 (62.5%) were resected
      totally, 2 (25%) subtotally, and 1 (12.5%) grossly. Postoperatively, 2 patients
      still remained slight hemiparesis, and 1 presented with mild facial paralysis.
      Among the 6 pons tumors 3 were removed totally and 3 subtotally. There were no
      postoperative neurological deficits. All the other tumors were resected
      completely without neurological dysfunction observed, however, one patient with a
      cholesteatoma failed to demonstrate apparent improvement in his diplopia.
      CONCLUSION: Microsurgical treatment of posterior cranial fossa tumors via keyhole
      approaches, with safe, succinct and minimally invasive property, is one of the
      promising directions in modern neurosurgery.

PMID- 15854479
TI  - [Neuronavigation and electrocorticography monitoring in resection of brain
      cavernous malformations].
AB  - OBJECTIVE: To investigate the indications, technical considerations, and effects
      of neuronavigation and electrocorticography (ECOG) monitoring in resection of
      brain cavernous malformations (CM). METHODS: From 1997 to 2003, 70 patients with
      CM, 53 males and 17 females, aged 33 (8 - 62), underwent resection of CM using
      neuronavigation and neurophysiological monitoring. The first episodes included
      hemorrhage (31 cases, 44.3%), seizure (29 cases, 41.4%), headache (5 cases,
      7.1%), and focal neurological deficit (4 cases, 5.7%). One case was asymptomatic
      (1.4%), only discovered during physical examination. The size of CM focus was 21
      mm (5-50 mm). The depth of tumor measured from the surface was 3-70 mm. Six
      patients had multiple lesions. The foci were located deep in the white matter of
      hemispheres in 39 cases, within the brainstem in 9 cases, within the basal
      ganglia or thalamus in 11 cases, within the cerebellum in 5 cases, and within the
      optic nerve in 1 case. Preoperatively a MRI procedure using 5 skin markers was
      performed with the data transferred to a neuronavigation workstation, thus
      reconstructing a three-dimensional image of the tumor. Supratentorial subcortical
      lobar cavernomas underwent microsurgery through sulcus and fissure approach. ECOG
      monitoring was performed on 29 patients with seizure during the operation and
      bipolar electrocoagulation on functional cortex was conducted. Follow-up was
      conducted for 19.4 months (6-24 months). RESULTS: No intraoperative death was
      found. Postoperative disability rate was 8.6%. Complete removal of the lesion
      demonstrated by postoperative MRI was obtained in all patients. New transitory
      neurological deficits occurred in 4 patients after operation and recovered within
      1 month. Hemiparesis developed in 1 patient with thalamus CM (1.4%) and facial
      paralysis developed in 1 patient with pons CM, and both recovered in 6 mouths.
      Nineteen out of the 24 patients with preoperative seizure history (79.2%) were
      postoperatively free of seizure, five (20.8%) of them showed improvement.
      CONCLUSION: Patients with asymptomatic CM can be kept under observation. CM deep
      in brain after the first bleeding is the indication of surgical treatment.
      Combination of neuronavigation and neurophysiological monitoring contributes to
      safety of operation and decrease of postoperative disability rate.

PMID- 15854481
TI  - [Minimally invasive surgery of the spinal cord hemangioblastoma].
AB  - OBJECTIVE: To clarify and discuss the diagnosis and minimally invasive surgery of
      spinal cord hemangioblastoma. METHODS: The clinical data of 16 patients with
      spinal cord hemangioblastoma who were operated on between 1992 and 2001 were
      analyzed retrospectively with a review of the literature. RESULTS: Twelve
      patients were subjected to MRI examination, nine to spinal cord angiography, and
      six to preoperative embolization. Thirteen patients underwent complete excision,
      and three underwent partial excision due to massive bleeding and anterior
      location of the tumor in spinal cord. Eleven patients showed improvement of their
      symptoms, four no change at all, and tumor recurrence was seen in one patient
      with aggravation. CONCLUSION: MRI and spinal angiography are essential for
      preoperative diagnosis and surgical planning. Early diagnosis and microsurgical
      resection greatly preserve the neurological function of the patients.
      Preoperative embolization sometimes is helpful in surgery.

PMID- 15854482
TI  - [Clinical efficiency of interventional therapy on internal carotid-posterior
      communicating artery aneurysm].
AB  - OBJECTIVE: To evaluate the effect of endovascular embolization of internal
      carotid-posterior communicating artery (IC-PC) aneurysm. METHODS: 145 patients
      with IC-PC aneurysms underwent endovascular embolization through the
      microcatheter under digital subtraction angiography (DSA). Of the 145 cases, 55
      patients with 62 aneurysms were embolized by mechanical detachable spiral (MDS)
      and 90 patients with 106 aneurysms were embolized by Guglielmi detachable coil
      (GDC) or electrical detachable coil (EDC). RESULTS: 168 aneurysms in 145
      patients, 96 of which with 100% embolization, 45 with 95% embolization, 15 with
      90% embolization, and 12 with less than 90% embolization, were embolized
      successfully. During the surgery, aneurysm rupture occurred in 3 cases, cerebral
      vasospasm in 5, and cerebral infarction in 1 case. 118 cases were cured, 23
      improved, and 3 died. 17 patients were followed-up by DSA, 3 aneurysms recurred
      and 2 were totally embolized with EDC for the second time. CONCLUSION:
      Endovascular embolization is a safe and effective therapeutic method for IC-PC
      aneurysm.

PMID- 15854483
TI  - [Diagnostic role of SOX13 antibody in latent autoimmune diabetes of adults].
AB  - OBJECTIVE: To explore the diagnostic role of SOX13 antibody in latent autoimmune
      diabetes of adults (LADA). METHODS: Sera of 328 patients with slow-onset diabetes
      and 120 sex and age-matched healthy controls underwent radiochemical test to
      detect the positive rates of SOX13-Ab, glutamic acid decarboxylace antibody (GAD
      Ab) and carboxypeptidase H antibody (CPH-Ab). According to the GAD-Ab and CPH-Ab
      status the patients were divided into autoimmune (GAD-Ab and/or CPH-Ab positive,
      n = 130) and non-autoimmune (GAD-Ab and CPH-Ab negative, n = 198) diabetic
      subgroups. Then according to SOX13-Ab, GAD-Ab and CPH-Ab status, the diabetic
      patients were divided into 4 groups: SOX13-Ab positive, GAD-Ab positive, CPH-Ab
      positive, and antibody-negative group to compare their clinical characteristics.
      The effect of SOX13-Ab on islet beta-cell function was evaluated by comparison of
      C-peptide among the four subgroups. RESULTS: The positive rates of SOX13-Ab in
      the slow-onset diabetic patients (10.4%), autoimmune subgroup patients (13.1%),
      and non-autoimmune subgroup patients (8.6%) were all higher than that in the
      healthy controls (2.5%, all P < 0.05). Thirteen patients were positive for both
      SOX13-Ab and CPH-Ab (13/328, 4.0%), but only 2 were positive for both SOX13-Ab
      and GAD-Ab (2/328, 0.6%). The highest prevalence of SOX13-Ab was observed in the
      patients with the duration of disease ranging from 16 to 20 years. There were no
      differences in the clinical parameters between the SOX13-Ab positive and antibody
      negative diabetic patients. CONCLUSION: SOX13-Ab testing helps improve the
      sensitivity of screening for LADA. SOX13-Ab positive patients tend to have a
      longer course of disease and varied clinical manifestations.

PMID- 15854484
TI  - [Application of percutaneous transluminal angioplasty and stent placement at the
      third hepatic porta in treatment of Budd-Chiari syndrome].
AB  - OBJECTIVE: To evaluate percutaneous transluminal angioplasty (PTA) and stent
      placement at the third hepatic porta in treatment of Budd-Chiari syndrome (BCS).
      METHODS: Twenty patients with BCS, 12 males and 8 females, aged 17 to 53, with
      the main clinical symptom of abdominal distention and mild abdominal pain, were
      treated with PTA and stent placement: after the identification of the target
      vessel percutaneous puncture was performed at femoral or jugular vein and
      rendezvous procedure was used so as to conduct PTA or place a stent. Follow-up
      was made for 3 - 54 months. RESULTS: Operation was succeeded in all patients
      without severe complication with a clinical effective rate of 85%. Symptoms were
      gradually relieved in 17 cases. Restenosis occurred in 2 cases. One patient died
      from severe gastric bleeding and one formed thrombosis in the stent. CONCLUSION:
      A safe and effective new method for diagnosing and treating BCS, PTA and stent
      placement at the third hepatic porta has the same treatment value for BCS just as
      the operation at the second hepatic porta.

PMID- 15854485
TI  - [Clinical analysis of 39 cases of heterotopic gastric mucosa in the upper
      esophagus].
AB  - OBJECTIVE: To determine accurately the incidence of heterotopic gastric mucosa in
      the upper esophagus (HGMUE) in China, and to study the macroscopic and
      microscopic aspects of the lesions and to evaluate the clinical importance of
      HGMUE. METHODS: A prospective study was made among a total of 15,228 consecutive
      patients, 8,573 male and 6,655 female, aged 54 (8-95), undergoing gastroscopy.
      Disease histories of all patients were carefully inquired, especially those
      regarding possible complaints including discomfort of throat and swallowing pain
      and so on. Special care was taken in the upper esophageal sphincter area to make
      sure whether the area was adequately inspected. Biopsy specimens from aberrant
      mucosa were obtained and the sections were stained with haematoxylin and eosin,
      and Giemsa stain for Helicobacter pylori. RESULTS: HGMUE was found in 39 patients
      (0.26%) with an average age of 50. Five patients with H. pylori infection in
      heterotopic gastric mucosa also presented the infection in the stomach. The
      gastric mucosa was gastric body type in 8 patients, transitional type in 11
      patients, and antral pattern in 7 patients. Intestinal metaplasia was found in 5
      patients, and mild atypical hyperplasia in 2 patients. An impressive finding was
      coexistent erosive gastritis in 14 patients (35.9%), Barrett's esophagus in one
      patient (2.6%), peptic ulcer in 8 patients (20.5%), and a patient had the
      complication of constriction in the upper esophagus. CONCLUSION: HGMUE is not
      rare in China. The presence of inlet patches is possibly correlated with specific
      symptoms. There are some severe complications in HGMUE, especially esophageal
      constriction. Close surveillance should be taken for rare cases with metaplasia
      or dysplasia in HGMUE.

PMID- 15854486
TI  - [Phenotype and function of myeloid dendritic cells pulsed with hepatitis B virus
      antigens in patients with HBV-associated hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the characteristics of phenotype and function of
      myeloid dendritic cells (mDCs) pulsed with HBV antigens derived from HBV
      associated hepatocellular carcinoma (HCC) patients. METHODS: Peripheral blood
      mononuclear cells (PBMCs) were collected, using blood cell separator, from 21
      primary HCC patients and 4 healthy donors. mDCs were propagated in serum-free AIM
      V medium in the presence of cytokine cocktail, and pulsed with HBcAg or HBsAg.
      After 9 days' incubation, the phenotypic patterns of mDC were characterized by
      flow cytometry and the levels of IL-10 and IL-12 produced by mDCs were analyzed
      by ELISA. Autologous T cells proliferation stimulated by mDC was tested by non
      radioactive cell proliferation assay kit. RESULTS: The expression rates of CD80,
      CD86, CD40, and HLA-DR in the mDCs pulsed with HBcAg were 55% +/- 26%, 80% +/-
      13%, 70% +/- 13% and 73% +/- 24% respectively, significantly higher than those of
      the control group (29% +/- 25%, 35% +/- 18%, 44% +/- 26% and 45% +/- 23%
      respectively, all P < 0.05). Among the expression rates of surface molecules of
      the mDCs pulsed with HBsAg only the expression rate of HLA-DR was significantly
      higher than that of the un-pulsed mDCs (63% +/- 15% vs 45% +/- 23%, P < 0.05). T
      cell proliferation assay revealed an impaired allostimulatory capacity of mDCs in
      HCC and the stimulatory capacity of the mDCs pulsed with HBcAg to induce
      proliferation of autologous T cells was more powerful than that pulsed with HBsAg
      (P < 0.05). The levels of IL-10 and IL-12 produced by the mDCs pulsed with HBsAg
      were (35 pg/ml +/- 9 pg/ml and 135 pg/ml +/- 63 pg/ml respectively, both
      significantly lower than those pulsed with HBcAg (236 pg/ml +/- 95 pg/ml and 733
      pg/ml +/- 212 pg/ml respectively, both P < 0.05). CONCLUSION: Pulsation of mDCs
      in vitro by HBcAg or HBsAg enhance the expression of CD80, CD86, CD40, and HLA
      DR, and increase the ability of mDCs to stimulate the proliferation of autologous
      T lymphocytes.

PMID- 15854487
TI  - [Apoptosis of pulmonary alveolar macrophages in aged and adult rats: a
      comparative study].
AB  - OBJECTIVE: To investigate the role of alveolar macrophages (AM) in the initiation
      of multiple organ failure in the elderly (MOFE). METHODS: Three-month-old (adult)
      and 24-month-old (aged) males SD rats were used as experimental animals. Zymosan
      0.5 g/kg was used to establish animal model of MOFE, normal saline were used
      among the control rats. The rats were divided into 4 groups: aged model group,
      aged control group, adult model group, and adult control group. Twenty-four hours
      after the establishment of model, 6 surviving rats from each group were killed.
      The trachea, bronthi, and lungs were isolated and lavaged with normal saline. One
      minute later the bronchi-alveolar lavage fluid (BALF) was re-extracted. Cells
      were collected from the fluid and put into 24-well cell culture plate. The
      alveolar macrophages (AMs) adhered to the wall were collected, suspended again,
      cultured, re-collected, centrifuged, and isolated. Apoptosis of the enriched AM
      was measured by propidium staining and flow cytometry. Fluo-3.AM staining and
      flow cytometry were used to detect the intracellular free calcium. Mitochondrial
      membrane electric potential was detected by rhodamine 123 staining with flow
      cytometry. RESULTS: The apoptotic rate (APO) of AM in the aged rat models was
      43.4% +/- 8.4%, significantly higher than that of adult model rats (24.2% +/-
      3.0%, P < 0.01). Compared with the controls, the intracellular calcium increased,
      but mitochondrial Dgr;Psim decreased in the 2 model groups. CONCLUSION: The AM
      APO% of aged MOFE model increases. It may be one of the causes of difficulty to
      control the inflammation in the lung with MOFE and easiness to induce MOFE in
      elderly when their lungs are infected or injured. Changes of intracellular
      calcium and mitochondrial Dgr;Psim may play pivotal roles in apoptosis of AM.

PMID- 15854488
TI  - [Effect of acid suppression therapy for eradicating Helicobacter pylori infection
      on bismuth absorption from colloidal bismuth pectin].
AB  - OBJECTIVE: To investigate whether acid suppression therapy influences the
      absorption of bismuth from colloidal bismuth pectin (CBP). METHODS: 48 male SD
      rats were randomly divided into five groups to be administer with different
      medicines once a day for 14 days: group A1 (administered with CBP only and killed
      on the cessation day of administration), group B1 (administered with CBP only and
      killed 8 weeks after the cessation of administration), group A2 [administered
      with CBP + amoxicillin (AMO) + metronidazole (MTR) + losec and killed on the
      cessation day of administration], group B2 (administered with CBP + AMO + MTR +
      losec and killed 8 weeks after the cessation of administration), and control
      group (administered with distilled water). The kidney issue sections were
      counterstained after AMG development. The bismuth deposited in tissues was
      observed by microscopy. The gray level of kidney tissue sections were measured
      and compared through image processing program. The deposition of bismuth and the
      degrees of cell organ's impairment were observed by electron microscopy. By using
      electron probe microanalysis bismuth was identified from the chemical elements in
      the specimens. RESULTS: Under the light microscopy, black-brown granules were
      discovered in the cell bodies of the proximal convoluted renal tubule. The
      amounts of bismuth accumulated in kidney of the 2 quadruple therapy groups were
      much more than those of the 2 single compound therapy groups (all P < 0.05). The
      amount of bismuth accumulated in kidney on the cessation day of administration
      was more than that eight weeks later (both P < 0.01). Under electron microscopy,
      black-brown granules were observed exclusively in the lysosomes of the proximal
      convoluted renal tubule cell. Electron microscopy found cell impairment in the
      quadruple therapy groups. Impairment of these cells could be recovered 8 weeks
      after the cessation of administration. CONCLUSION: Acid suppression therapy
      causes an increase of absorption and accumulation of bismuth from CBP in the
      kidney. Bismuth can be accumulated in the cell bodies of proximal convoluted
      renal tubule after its absorption. The absorbed bismuth can be discharged out of
      the body via kidney. Large amounts of bismuth accumulation in kidney can impair
      the functions of proximal convoluted renal tubule cells.

PMID- 15854489
TI  - [Experimental study of dually targeting gene therapy system for pituitary
      adenomas].
AB  - OBJECTIVE: To construct a dually targeting gene therapy system for pituitary
      adenomas and investigate its effect. METHODS: Promoter hGHp containing human
      growth hormone gene was obtained from human genome and cloned into the plasmid
      pcDNA3.1/His A with the promoter cut to construct the recombinant plasmid
      pcDNA3.1/His A-hGHp. HSV-TK gene was obtained from the plasmid pcDNA3.1/His A-TK
      and integrated into the plasmid pcDNA3.1/His A-hGHp to construct the recombinant
      plasmid pcDNA3.1/His A-hGHp-TK. A GE7 gene delivery system-mediated human growth
      hormone promoter controlled gene therapy system was constructed by adding the
      mixture of GE7-polylysine and HA20-polylysine into the DNA solution. Human growth
      hormone-secreting pituitary adenoma cells of the GH3 line, human myeloma cells of
      the U-2OS line, and human oophoroma cells of the HO8910PM line were cultured and
      transfected with PBS or GE7 packaged pcDNA3.1/HisA-TK or pcDNA3.1/HisA-hGHp-TK.
      Western blotting was used to examine the expression of PBS or GE7 packaged
      pcDNA3.1/HisA-TK or pcDNA3.1/HisA-hGHp-TK protein, MTT method was used to detect
      the cell survival rate. Another GH3, U-2OS, and HO8910PM cells were cultured and
      transfected with PBS or GE7 packaged pcDNA3.1/HisA-TK or pcDNA3.1/HisA-hGHp-TK
      and then ganciclovir (GCV) was added. MTT method was used to examine the cell
      survival rates. GH3 cells were injected subcutaneously into the right axilla of
      200 SD nude rats loaded with human pituitary adenoma. Three weeks after the rats
      were randomly divided into 5 equal groups: PBS group in which PBS was injected
      into the tumor and GCV was injected peritoneally; GE7 group in which GE7
      polylysine and HA20-polylysine were injected into the tumor and GCV was injected
      peritoneally; without TK group in which GE7-packaged pcDNA3.1/His A-hGHp was
      injected into the tumor and GCV was injected peritoneally; without GCV group in
      which GE7-packaged pcDNA3.1/His A-hGHp-TK was injected into the tumor and PBS was
      injected peritoneally; and treatment group in which GE7-packaged pcDNA3.1/His A
      hGHp-TK was injected into the tumor and GCV was injected peritoneally. Peritoneal
      injection lasted 21 days for all groups. On the days 3, 7, 14, and 21 eight rats
      from each group were killed to measure the volume of tumor. The survival rate of
      the rest 8 rats was observed. RESULTS: A dually targeting gene therapy system for
      pituitary adenoma was composed successfully. HSV-TK protein was expressed in the
      GH3 cells but not in the U-2OS and HO8910PM cells after transfection of GE7
      packaged pcDNA3.1/HisA-hGHp-TK; and was expressed in the GH3 and HO8910PM cells
      but not in the U-2OS cells after transfection of GE7-packaged pcDNA3.1/HisA-TK.
      Transfection of GE7-packaged pcDNA3.1/HisA-hGHp-TK and addition of GCV
      significantly decreased the survival rate of the GH3 cells, but did not influence
      the survival rates of the U-2OS and HO8910PM cells. Transfection of GE7-packaged
      pcDNA3.1/HisA-TK and addition of GCV significantly decreased the survival rate of
      GH3 and HO8910PM cells but did not influence the survival of the U-2OS and
      HO8910PM cells. When the GH3 cells were transfected with GE7-packaged
      pcDNA3.1/HisA-hGHp-TK with the addition of GCV of the concentration of 4 mg/L the
      survival rate decreased to 10%, when the GCV concentration was raised to 8 mg/L
      the survival rate of the GH3 cells was < 5%. Three days after the beginning of
      treatment the tumor volume of different groups of rats increased at different
      degrees and the tumor was smallest in the treatment group in comparison with the
      other groups (all P < 0.05). Seven days after the beginning of treatment the
      tumor volume of the treatment group significantly decreased and the tumors of the
      other groups still increased (all P < 0.001). The survival time of the treatment
      group was over 120 days, significantly longer than those of the other groups (all
      about 40 days). CONCLUSION: GE7 system-mediated hGHp controlled gene therapy
      system is hopeful to be the targeted therapeutic strategy for pituitary adenomas.

PMID- 15854490
TI  - [Role of MyD88-dependent nuclear factor-kappaB signaling pathway in the
      development of cardiac hypertrophy in vivo].
AB  - OBJECTIVE: To investigate the role of MyD88-dependent nuclear factor-kappaB (NF
      (B) activation signaling pathway in the development of cardiac hypertrophy in
      vivo. METHODS: Dominant negative myeloid differentiation protein (dn-MyD) 88
      fragment was inserted into pShuttle plasmid and then fused into adenovirus so as
      to construct Ad5-dn-MyD88. Some Sprague-Dawley (SD) rats underwent banding of
      aorta (aorta binding group) and some SD rats underwent sham operation (sham
      operation group). Part of the rats in the aorta banding group were transfected
      with Ad5-dn-MyD88 into the myocardium tissue (Ad5-dn-MyD88 transfection group) or
      adenovirus expressing dnMyD88 (Ad5-GFP) (control group) so as to determine the
      effect of blocking down stream of MyD88 signaling on the development of cardiac
      hypertrophy. Three days after the hearts of some rats from the 4 groups were
      collected and Western blotting was used to detect the expression of dn-MyD88
      protein and fluorescent microscopy was used to detect the expression of GFP.
      Three weeks after the beginning of experiment the hearts were collected to
      calculate the heart weight/body weight (HW/BW) ratio and extract the plasma
      protein and nuclear protein. Electrophoretic mobility shift assay (EMSA) was used
      to determine the NFkappaB binding activity. Western blotting was used to examine
      the phosphorylation of IkappaBalpha and IKKalpha/beta with appropriate specific
      anti-phospho antibodies. RESULTS: Flag and dn-MyD88 were effectively expressed 3
      days after the transfection of Ad5-dn-MyD88 into the myocardium. Three weeks
      after the HW/BW ratio was 0.47 +/- 0.01 in the aorta banding group, significantly
      higher, by 37.8%, than that of the sham operation group (0.34 +/- 0.01, P <
      0.01), and was 0.41 +/- 0.02 in the Ad5-dn-MyD88 transfection group,
      significantly lower, by 11.58%, than that of the aorta banding group (P < 0.01);
      the myocardial ANP protein expression level of the aorta binding group was
      significantly higher, by 43.5%, than that of the sham operation group (P < 0.01)
      and 36.2% higher than that of the Ad5-dnMyD88 transfection group (P < 0.01); the
      ANP/GAPDH in the aorta binding group was significantly higher than that of the
      sham operation group (P < 0.01) and that of the Ad5-dn-MyD88 transfection group
      (P < 0.01); the NF-kappaB binding activity in the myocardium of the aorta banding
      group was 9.94 +/- 1.58, significantly higher, by 144.8%, than that of the sham
      operation group (4.06 +/- 0.52, P < 0.01) and significantly lower, by 41.8%, than
      that of the Ad5-dn-MyD88 transfection group (5.79 +/- 0.52, P < 0.05); the
      phospho-(p-) IkappaBalpha level and p-IkappaBalpha/IkappaBalpha of the aorta
      binding group were significantly higher than those of the sham operation group (P
      < 0.01) and significantly higher, by 26.7%, than that of the Ad5-dn-MyD88
      transfection group (P < 0.05); the p-IKKalphabeta/IKKalphabeta in the myocardium
      of the aorta binding group was significantly higher, by 318.0%, than that of the
      sham operation group (P < 0.01), and significantly higher, by 77.4%, than that of
      the Ad5-dn-MyD88 transfection group (P < 0.01). CONCLUSION: MyD88-dependent
      NFkappaB signaling is a novel pathway for inducing the development of cardiac
      hypertrophy in vivo and blocking MyD88 mediated signaling pathway attenuates the
      development of cardiac hypertrophy.

PMID- 15854492
TI  - [Castleman disease complicated with paraneoplastic pemphigus--a case report].

PMID- 15854493
TI  - [Evidence-based medicine: the new model of medical practice].

PMID- 15854494
TI  - [Payment of living donors for solid human organ--feasibility and ethics issue].

PMID- 15854495
TI  - [Prevention and treatment of obstetric brachial plexus injury(I)].

PMID- 15854496
TI  - [New choice of therapy of pulmonary hypertension: endothelin receptor
      antagonist].

PMID- 15854497
TI  - [Importance to the application of abdominal scan skill of CT and MRI].

PMID- 15854498
TI  - [Methods of modern clinical research design].

PMID- 15854499
TI  - [Novel use of CO2 splenoportography: via spleen percutaneous fine needle puncture
      portography].

PMID- 15854500
TI  - [Noninvasive image diagnosis of Budd-Chiari syndrome and its evaluation study].

PMID- 15854501
TI  - [Imaging diagnosis of hepatocellular carcinoma].

PMID- 15854502
TI  - [Indications of clinical uses of contrast agents for MR imaging of liver].

PMID- 15854503
TI  - [Improvement of the diagnosis of small bowel diseases with modern medical imaging
      technics].

PMID- 15854504
TI  - [Budd-Chiari syndrome with occlusion of hepatic vein: multi-slice spiral CT
      diagnosis and its clinical significance in the treatment].
AB  - OBJECTIVE: To evaluate the multi-slice spiral CT dynamic enhancement features and
      the diagnostic value of CT angiography in Budd-Chiari syndrome with occlusion of
      hepatic vein (HVBCS), and to assess the CT clinical significance in the treatment
      of HVBCS. METHODS: Twenty-one patients with HVBCS confirmed by digital
      subtraction angiography (DSA) were retrospectively analyzed. All patients
      received multi-slice spiral dynamic enhancement scans within 2 weeks before DSA.
      The relevant vein vessels were reconstructed respectively with Maximum Intensity
      Projection (MIP), Volume Rendering (VR) and Oblique Reformat techniques. The
      course of disease was less than three months in four patients, more than three
      months in seventeen patients. RESULTS: In the four patients with the course of
      disease of less than three months, CT showed global liver enlargement with
      diffuse hypodensity on plain scans and patchy enhancement in caudate lobe and
      perihilar areas on post-contrast CT scans, and the enhancement field spread to
      larger area as the time of scans delayed. In the seventeen patients with the
      course of disease of more than three months, plain CT scans showed abnormalities
      of liver morphology and hypodensity either in atrophic areas or in the periphery
      of the liver. On post-contrast CT scans, the hypodensity areas showed poor and
      heterogeneous enhancement, and hepatic drainage veins in these areas obstructed,
      whereas in hepatic veins drainage normal areas hepatic parenchymal showed
      homogeneous enhancement, their drainage veins had at least one patent hepatic
      vein or a dilated accessory hepatic vein that can provide adequate collaterals.
      Hepatic CT enhancement features were closely related to the occlusion location of
      hepatic vein and collateral drainage veins. In twenty-one patients, a total of 42
      hepatic veins were occluded. Among them, 9 left hepatic veins, 12 middle hepatic
      veins, 16 right hepatic veins, and 6 accessory hepatic veins were occluded. The
      accuracy rate of hepatic veins occlusion showed on transverse scans and CT
      angiography were 61.9% and 100% respectively. CONCLUSION: Multi-slice spiral
      dynamic enhancement scans can accurately reflect the changes of intrahepatic
      hymodynamics. Transverse scans combined with CT angiography can explicitly show
      the location of hepatic veins occlusion and collateral circulation in HVBCS,
      which is of important clinical significance in the treatment of HVBCS.

PMID- 15854505
TI  - [Portal vein involvement by hepatocellular carcinoma: diagnosis with three
      dimensional contrast-enhanced MR angiography].
AB  - OBJECTIVE: To assess the accuracy of three-dimensional contrast-enhanced magnetic
      resonance angiography (3D CE MRA) in evaluating the portal vein involvement in
      patients with hepatocellular carcinoma. METHODS: Ninety patients with
      hepatocellular carcinoma underwent 3D CE MRA of the portal venous system, using a
      high-field 1.5 T MR machine and a body coil and using Gd-DTPA as contrast
      material, before hepatic surgery or interventional therapy. The acquired source
      images of the examination were reconstructed into 3D MRA image similar to that of
      conventional X-ray angiography. The patency of the main, right and left portal
      veins was evaluated. A total of 270 veins were assessed. The patency was
      classified as normal or involved. The involvement included encasement, occlusion,
      and tumor thrombosis. The 3D CE MRA diagnoses were compared with the surgical
      pathologic, intra-operative sonographic, and X-ray portographic findings.
      RESULTS: 74 of the 75 involved portal veins and 188 of the 195 noninvolved portal
      veins confirmed by surgery or X-ray portography were detected by 3D CE MRA with
      an overall sensitivity rate of 99%, specificity rate of 96%, positive predictive
      value of 91%, and negative predictive value of 99%. The accuracy in diagnosis of
      the main portal vein was 100%. 3D CE MRA resulted in 7 false-positive
      interpretations involving 6 left portal veins and 1 right portal vein. One false
      negative diagnosis was made on the right portal vein. CONCLUSION: 3D CE MRA is
      quite accurate in evaluation of portal vein involvement in patients with
      hepatocellular carcinoma.

PMID- 15854507
TI  - [Apolipoprotein B is associated with metabolic syndrome in Chinese pedigrees with
      familial hyperlipidemia].
AB  - OBJECTIVE: To investigate the prevalence of metabolic syndrome (MS) as well as
      the potential predictors in families with familial combined hyperlipidemia
      (FCHL), familial hypertriglyceridemia (FHTG), familial hypercholesterolemia (FH)
      and normolipidemic families in China. METHODS: The prevalence of MS was
      identified among 70 different families with 560 individuals aged > or = 20,
      including 43 FCHL families with 379 individuals, 3 FHTG families with 30
      individuals, 16 FH families with 102 individuals and 8 normolipidemic families
      with 49 individuals. Diagnosis of MS was based on the modified criteria of
      National Cholesterol Education Program, US, substituting body mass index for
      waist circumference. Multivariate logistic regression was used to analyze the
      association between MS and different pedigrees. RESULTS: MS was identified in
      60.7% of the FCHL patients and 71.4% of the FHTG patients. The prevalence of MS
      in the family members was 36.7% for the FCHL families, 33.3% for the FHTG
      families, 17.6% for the FH families, and 16.3% for the normolipidemic families,
      with an odds ratio (OR) of 2.97 (95% CI 1.29 to 7.07) in the FCHL families
      compared with in the normolipidemic families. Multivariate logistic regression
      showed an association between apolipoprotein (apo) B and MS with an OR of 1.05
      (1.03 to 1.07) in the FCHL families, an OR of 1.26 (1.03 to 1.55) in the FHTG
      families, and an OR of 1.07 (1.01 to 1.12) in the FH families, independent of
      variables such as age, gender, apoA1, and LDL cholesterol, but showed no
      association in the normolipidemic families (P >0.05). Similarly, apo A1 provided
      an OR of 0.95 (0.94 to 0.97) in the FCHL families and an OR of 0.94 (0.90 to
      0.99) in the FH families, but neither in the FHTG families nor in the
      normolipidemic families (both P >0.05). CONCLUSION: Apo B may be regarded as a
      relevant factor in the assessment of MS in FCHL, FHTG and FH families in Chinese.
      However, this finding needs to be verified by prospective studies in diverse
      ethnicities and warrants additional studies to elucidate the possible mechanisms
      linking apoB to MS.

PMID- 15854508
TI  - [Expression and clinical significance of inducible co-stimulator on peripheral
      blood T lymphocyte subsets in patients with systemic lupus erythematosus].
AB  - OBJECTIVE: To investigate the expression of inducible co-stimulator (ICOS) and
      other immunological molecules on peripheral blood T lymphocyte subsets in
      patients with systemic lupus erythematosus (SLE) and to find out the relationship
      with disease-activity, disease-stage and the contents of anti-dsDNA antibody and
      immunoglobulin in serum so as to pave the way for further studying the possibly
      immunologically pathological role of ICOS in SLE. METHODS: Peripheral blood
      samples were collected from 51 patients with SLE, 3 males and 22 females. Three
      color flow cytometry was used to detect the levels of ICOS, CD45RO, CD45RA, and
      HLA-DR expression on the peripheral blood T lymphocytes subsets. The results were
      analyzed along with the disease-activity, disease-stage, contents of anti-dsDNA
      antibody and immunoglobulin in serum. Thirty healthy subjects were used as
      controls. RESULTS: Compared with the healthy subjects the level of ICOS
      expression on the peripheral blood CD4+ and CD8+ T cells in the patients with SLE
      during active- and stable-stages were significantly increased (all P < 0.05), but
      there was no significant difference between the last two group patients (P > or =
      0.05); In the same patients, the level of ICOS expression on the peripheral blood
      CD4+, CD8+, CD45RO+, CD4+CD45RO+ and CD8+CD45RO+ cells in active-stage were
      significantly increased compared with those in stable-stage (P <0.05); The level
      of ICOS expression on the peripheral blood CD45RO+ cells in the untreated primary
      patients was higher than those with disease-relapse (P <0.05); The levels of ICOS
      expression on the peripheral blood CD45RO+ and CD4+CD45RO+ cells were
      significantly increased in the patients with serum anti-dsDNA antibody(+) and the
      patients with aberrantly high content of immunoglobulin compared with those of
      the patients with serum anti-dsDNA antibody(-) and the patients with normal
      content of immunoglobulin, respectively (all P < 0.05). CONCLUSION: ICOS is
      aberrantly highly expressed on certain peripheral blood T lymphocyte subsets in
      patients with SLE, which is related to disease-activity, disease-stage and the
      contents of serum anti-dsDNA antibody and immunoglobulin, thus ICOS may play a
      role in SLE pathogenesis.

PMID- 15854509
TI  - [Construction and evaluation of the property of decellular porcine aortic valve].
AB  - OBJECTIVE: To construct decellular porcine aortic valve (PAV) and to observe the
      existence of porcine endogenous retrovirus (PERV) and valve scaffold structure
      before and after implantation. METHODS: (1) Porcine aortic valve was obtained.
      The cellular components of PAV were completely removed by using detergent and
      nucleotidase solution combined with alteration of osmosis. (2) The decellular
      underwent HE staining and light microscopy and detection of its physical and
      chemical properties. (3) 20 pieces of decellular PAV were implanted into dogs. On
      e month later blood samples of the dogs were collected. PCR and RT-PCR were used
      to detect the PERV expression in 20 samples of pig's peripheral blood, 20 fresh
      PAVs, cultured pig kidney cells of the PK15 line (as positive control),
      decellular PAVs implanted into the dogs, and 10 samples of dogs' peripheral
      blood. (4) Small pieces of decellular PAVs were implanted into the subcutaneous
      tissues of 6 rabbits at the back, 6 pieces for one rabbit, and then extracted by
      the ends of the 4th, 6th, 8th and 10th week respectively after implantation to
      undergo HE staining and light microscopy. RESULTS: (1) Almost all cellular
      components in the PAVs had been removed after decellularization; the soluble
      protein contents lost markedly [(0.238 +/- 0.038)% vs. (0.484 +/- 0.116)%]; the
      water content of the decellular tissues increased significantly [(92.16 +/-
      1.48)% vs. (89.2 +/- 1.55)%]; however, the decellular PAVs still maintained their
      excellent fibrous scaffold structure, and their shrinkage temperature and tension
      at fracture were not significantly changed [(72.0 +/- 0.7) degrees C vs. (71.2 +/
      0.8) degrees C, and (448.7 +/- 18.65)g/mm2 vs. (540.7 +/- 19.46)g/mm2
      respectively]. (2) Agarose gel electrophoresis of all fresh PAVs and porcine
      peripheral blood samples showed a 219 bp band, which was 90% to 97% homologous
      with PERV-C gene, and the sequence of which is published in Medline. No 219 bp
      amplified band was found in all decellular PAVs and the peripheral blood samples
      of the dogs implanted with decellular PAV one month after the implantation. (3)
      The PAVs implanted in rabbit body showed very slight tissue reaction. Neutrophil,
      lymphocyte and plasmacyte infiltration were seen 4 weeks after; such inflammatory
      cell infiltration decreased markedly and the peripheral portions of the
      decellular PAVs began to be absorbed by the end of the 6th week after
      implantation. The decellular PAVs were completely absorbed without fibrosis or
      scar formation in the implantation area by the end of the 10th week. CONCLUSION:
      (1) The cellular components of PAV can be completely removed, the excellent
      fibrous scaffold structure and mechanical strength of aorta valve can be
      maintained, and the antigenicity is very weak. Subcutaneous implantation
      investigation shows that decellular PAV is an absorbable and degradable
      biological material. (2) There is PERV-C in PAV that can be removed after
      decellularization. PERV-C reaction is negative in the peripheral blood samples of
      the recipients implanted with decellular PAV.

PMID- 15854510
TI  - [Transforming growth factor-beta1 stimulates matrix metalloproteinase-9
      production through ERK activation pathway and upregulation of Ets-1 protein].
AB  - OBJECTIVE: To investigate the molecular mechanism of transforming growth factor
      beta1 (TGF-beta1) in regulating the production of matrix metalloproteinase-9 (MMP
      9) protein. METHODS: Mouse immortal podocyte cells were cultured. Different
      concentrations (1, 2, and 5 ng/l) of TGF-beta1 were added into the culture
      medium. Cell culture without TGF-beta1 stimulation was used as control group. The
      activity of MMP-9 in the supernatant of the culture medion was assayed by gelatin
      zymography, expression of MMP-9 mRNA was assessed by RT-PCR; the activation of
      ERK pathway and the level of a transcriptional factor Ets-1 protein was analyzed
      by Western blotting. PD98059, a specific inhibitor of ERK1/2 activation, was
      added into the culture fluid of the podocytes for 30 minutes, than 2 ng/ml TGF
      beta1 was added. The above mentioned tested were conducted to observe the
      influence of the inhibitor of ERK1/2 activation. RESULTS: The MMP-9 activity was
      very week in the supernatant of culture fluid of the control group and was
      increased in the TGF-beta1 groups dose-dependently. After the podocytes were co
      incubated with 1 ng/ml TGF-beta1 for 24 hours, the MMP-9 activity was 26.86 times
      that of the control group (P < 0.01). Since the 12th hour after co-incubation
      with 2 ng/ml TGF-beta1 the MMP-9 activity in the supernatant of culture fluid
      began to be significantly increased and remained at high level till the 48 th
      hour. RT-PCR showed that low-level MMP-9 mRNA expression in the control group.
      After stimulation of 2 ng/ml TGF-beta1 for 6 hours the MMP-9 mRNA expression was
      2.71 times that of the control group (P < 0.01) and the high-level expression
      lasted 24 hours. Western blotting showed low-level Ets-1 protein in the control
      group. At the time point of 12 th hour after stimulation of TGF-beta1 the Ets-1
      protein expression was increased in all the three TGF-beta1 groups. After
      stimulation with 2 ng/ml TGF-beta1 for 4 hours the Ets-1 protein expression was
      2.71 times that of the control group (P <0.01). After pretreatment of the
      podocyte with PD98059 for 30 minutes, the added 2 ng/ml TGF-beta1 failed to
      increase the MMP-9 activity and up-regulate the MMP-9 mRNA expression.
      CONCLUSION: TGF-beta1 stimulates the production of MMP-9 by activation of
      cytoplasmic ERK signaling pathway and upregulation of Ets-1 expression.

PMID- 15854511
TI  - [The influence of early vascular rejection on late rejection in first cadaveric
      renal transplantation].
AB  - OBJECTIVE: To explore the influence of early completely reversal vascular
      rejection on late rejection. METHODS: The data of 1062 patients who received
      their first cadaveric transplants between May 1988 and March 2003 were analyzed
      respectively. The patients were divided into 2 groups: group with vascular
      rejection occurring within 1 month postoperatively (n = 45), and group without
      vascular rejection (n = 1017). Follow up was performed for at least 6 months. The
      influence of demographic characteristics (transplant age, sex), transplant
      variables (complement dependent cytotoxicity test, cold/warm ischemia time), and
      post-transplant variables (immunosuppressive agents for the prevention of acute
      rejection,) were analyzed. RESULTS: There were no differences in the age at
      transplantation, sex, complement dependent cytotoxicity test, cold/warm ischemia
      time, immunosuppression agent protocol, and serum creatinine during follow-up
      between the recipients of these two groups. Late rejection, including acute
      interstitial rejection, borderline rejection, and chronic rejection, occurring
      one month after transplantation was 2.22% (1/45) in the vascular rejection group,
      significantly lower than that of the no vascular rejection group (12.59%,
      128/1017, P = 0.034) CONCLUSION: Early completely reversal vascular rejection can
      reduce the rate of late rejection.

PMID- 15854512
TI  - [Effects of teriparatide and alendronate on bone mineral density of osteoporotic
      rats].
AB  - OBJECTIVE: To investigate the effects of teriparatide (hPTH1-34, PTH) and
      alendronate (Alen) on bone turnover rate and bone mineral density (BMD) of
      ovariectomized (OVX) osteoporotic rats. METHODS: 70 female 6-month-old Wistar
      rats were randomly divided into 7 groups: (1) baseline group: killed immediately
      as baseline controls; (2) sham operation group: injected subcutaneously with
      normal saline (NS) as normal controls; (3) OVXb group: underwent ovarietomy (OVX)
      and killed 6 weeks after OVX as pre-therapeutic controls; (4) OVXe group:
      injected with NS subcutaneously and then sacrificed 14 weeks after OVX as
      controls by the end of treatment; (5) PTH group: PTH 40 microg.kg(-1).d(-1) was
      administered; (6) Alen group: Alen 100 microg.kg(-1).d(-1) was administered; (7)
      A + P group: PTH 40 microg.kg(-1).d(-1) and Alen 100microg.kg(-1).d(-1) were
      administered. In groups 4 approximately 7, different medicines were injected
      subcutaneously QD 5 times per week from the 6th week to the 14th week after OVX
      and then the rats were killed and their right femurs, lumbar vertebrae, and
      samples of blood and urine were collected. Absorptometry was used to measure the
      BMD of the right femur and lumbar vertebrae. The serum calcium, phosphate,
      creatinine, alanine transaminase, and alkaline phosphatase (ALP) activity were
      measured by automatic biochemical analysis. The bone resorption marker urine
      deoxypyridinoline/creatinine (UDpd/Cr) level was measured by enzyme-linked
      immuosorbent assay. RESULTS: Six weeks after OVX the ALP and UDpd/Cr levels in
      the OVXb group were 101 U/L +/- 59 U/L and (118 +/- 32) x 10(-6) respectively,
      both significantly higher than those of the baseline group (58 U/L +/- 10 U/L and
      (48 +/- 34) x 10(-6) respectively, both P < 0.01) and the BMD results of the OVXb
      group were all significantly lower than those in the baseline group (all P <
      0.01), which indicated that an OVX osteoporotic rat model was established
      successfully. The ALP and UDpd/Cr levels of the Alen group were 61 U/L +/- 28 U/L
      and (17 +/- 39) x 10(-6), significantly lower than those of the PTH group 120 U/L
      +/- 36 U/L and (111 +/- 26) x 10(-6) respectively, both P < 0.01) and the UDpd/Cr
      levels of the A + P group were between those of the Alen group and those of the
      PTH group. The BMD levels of the femur and lumbar vertebrae of the PTH, Alen, and
      A + P groups were all significantly higher than those of the control groups (all
      P < 0.01), and were similar to or higher than those of the sham operation group
      without significant differences between the PTH and Alen groups. The BMD level of
      the lumber vertebrae of the A + P group were significantly higher than those in
      the PTH group (all P < 0.05), and the femoral BMD results of the A + P group were
      significantly higher than those in the PTH and Alen groups (all P < 0.01).
      CONCLUSION: PTH and Alen are all effective on osteoporosis. In particular, the
      combination of PTH and Alen is more effective on increasing the BMD level.

PMID- 15854513
TI  - [Expression and clinical significance of MAPK in non-small cell lung cancer].
AB  - OBJECTIVE: To explore the expression of p38,ERK1 (extracellular signal regulated
      kinases1) and JNK1 (c-jun NH2-terminal kinases1), subtribes of MAPK (mitogen
      activated protein kinases), and their clinical implication in non-small cell lung
      cancer (NSCLC) cells. METHOD: Immunohistochemistry was used to detect the
      expression of p38, ERK1, JNK1, and ras in the resected specimens of non-small
      cell lung cancer from 73 patients. The relation between p38, ERK1, and JNK1 and
      clinicopathological factors were analyzed by Mann-Whitney u test, chi(2) test,
      and Fisher precise probability method. The relations between ras and various
      subtribes of MAPK were analyzed by chi(2) test; the post-operative clinical
      effects were detected by Kaplan-Meier curve. RESULTS: Expression of p38 was
      related with lymph node metastasis (P = 0.000) and TNM staging (P = 0.001).
      Expression of ERK1 was correlated with pathological type (P = 0.015), lymph node
      metastasis (P = 0.000) and TNM staging (P = 0.000). Expression of JNK1 was
      related with the tumor location (P = 0.005). ras expression was correlated with
      p38 (P = 0.003) and ERK1 (P = 0.012). Univariate analysis showed that TNM staging
      (P = 0.0000), lymph node metastasis (P = 0.0000), tumor differentiation (P =
      0.0000), p38 (P = 0.0001), JNK1 (P = 0.0232), and ras (P = 0.0022) were of
      prognostic significance. Multivariable analysis showed that NSCLC patients with
      negative expression of p38 (P = 0.035), clinical I stage (P = 0.026), negative
      lymph node metastasis (P = 0.044) and fine tumor differentiation (P = 0.020)
      might have a better prognosis. CONCLUSION: Among the subtribes of MAPK, p38 may
      be of use to assess lymph node metastasis and TNM staging, ERK1 may be of use to
      evaluate histological type, lymph node metastasis and TNM staging, and JNK1 to
      assess the tumor location. ras may increase the expression of p38 and ERK1. p38,
      as well as some clinicpathological factors, including TNM staging, lymph node
      metastasis and tumor differentiation are prognostic factors of NSCLC.

PMID- 15854514
TI  - [Preparation of 99mTc-labeled SZ-51 F(ab)2 and radioimmunoimaging in dogs with
      pulmonary embolism].

PMID- 15854515
TI  - [Mutation on the 4th and 5th extrons of COCH gene in Meniere's disease].

PMID- 15854516
TI  - [Experimental study on the prevention of vascular prosthetic infection with an
      antibiotic-bonded dacron graft].

PMID- 15854517
TI  - [Chronic arsenic intoxication--a case report ].

PMID- 15854518
TI  - [Efficacy of radiofrequency ablation in the treatment of liver neoplasms and its
      influencing factors].

PMID- 15854519
TI  - [SRY negative 46XX male syndrome--a case report].

PMID- 15854522
TI  - [Non-drug treatment of atrial fibrillation].

PMID- 15854521
TI  - [New age of systems medical biology].

PMID- 15854523
TI  - [Cloning and functional analysis of melanocortin 4 receptor mutation gene F261S].
AB  - OBJECTIVE: To evaluate the function change of the melanocortin 4 receptor (MC4R)
      protein with mutation of F261S. METHODS: Human embryonic cells of the HEK293 line
      were cultured. Wild-type genomic DNA and F261S mutation human melanocortin 4
      receptor genes from the genomic DNA of aproband of homozygotic F612 mutation were
      amplified and cloned into a topo-TA eukaryotic expression plasmid vector. After
      the wild-type and F261S mutated proteins were expressed in HEK293 cells, alpha
      MSH (10(-11) approximately 10(-5) mmol/L) was added, then the intracellular cAMP
      was detected with dual luciferase reporter assay system. RESULTS: When the
      concentration of alpha-MSH added was 10(-9) approximately 10(-8) mmol/L, the
      intracellular alpha-MSH concentration of the cells transfected with wild-type
      MC4R gene was significantly higher than that of the cells transfected with F261S
      mutation gene (P < 0.05). When the concentration of alpha-MSH added went to 10(
      7) approximately 10(-5) mmol/L, the differences became even more significant (all
      P < 0.01). CONCLUSION: The novel MC4R mutation F261S undermines the signal
      transduction. It may be the possible reason leading to monogenic mutation obesity
      in Chinese.

PMID- 15854524
TI  - [Proliferation of type II collagen specific T cell response and antibody
      formation in rheumatoid arthritis and their relations to HLA-DR4].
AB  - OBJECTIVE: To investigate the proliferation of type II collagen specific T cell
      response and antibody formation in rheumatoid arthritis (RA) and their relations
      to HLA-DR4 subtype. METHODS: Peripheral blood mononuclear cells and serum were
      obtained from 62 RA patients, 14 males and 48 females, aged 43 +/- 29. CII263-272
      decapeptide and the peripheral blood mononuclear cells (PBMCs) from 62 RA
      patients were co-incubated for 5 approximately 7 days. MTT method was used to
      examine the T cell proliferation. The serum antibodies specific to CII 263-272
      were examined by ELISA. HLA-DR typing was detected in 40 patients by SSP-PCR.
      RESULTS: Positive T cell response challenged by CII 263-272 decapeptide was
      observed in 38 (61.3%) RA patients. The positive rate of CII 263-272 antibody was
      66.7% in the T cell response positive group, significantly higher than that of
      the T cell response negative group (34.6%, P < 0.05). The T cell response rate of
      the CII 263-272 antibody positive group was 69.7%, significant higher than that
      of the negative group (42.1%, P < 0.05). In all patients, the stimulation index
      (SI) of T cell proliferation to CII263-272 peptide was positively correlated with
      the level of antibody (r = 0.68, P < 0.01). HLA-DR4 allele was detected in 16 out
      of the 40 patients. Positive T cell response and presence of antibody to CII 263
      272 were not associated with HLA-DR4 phenotype. CONCLUSION: The formation of CII
      antibody may be related to B cell activation mediated by CII specific T cell.

PMID- 15854525
TI  - [Effects of angiotensin II and aldosterone on NF-kappaB binding activity in
      hepatic stellate cells].
AB  - OBJECTIVE: To investigate the signal transduction mechanism underlying the
      effects of angiotensin II (AngII) and aldosterone (Aldo) on nuclear factor-kappaB
      (NF-kappaB) DNA binding activity. METHODS: Sixty male Wistar rats were randomly
      divided into 4 groups: model group (Mo group), injected with CCl(4)
      subcutaneously twice a week to establish a model of hepatic fibrosis; perindopril
      group (Pe group), injected with CCl(4) subcutaneously twice a week and perfused
      with perindopril once a day; losartan group (Lo group), injected with CCl(4)
      subcutaneously twice a week and perfused with losartan once a day; and control
      group (Nc group), injected with olive oil subcutaneously. The rats were killed in
      batches respectively 4 and 6 weeks after and their livers were collected to
      undergo Masson staining and be observed by light microscope. Electrophoretic gel
      mobility shift assay (EMSA) was used to detect the NF-kappaB DNA binding activity
      in the liver tissues. Western blotting was used to detect the expression of
      IkappaBalpha in the plasma protein. Hepatic stellate cells (HSCs)-T6 were
      cultured and preincubated for 1 h or not with U0126 (an inhibitor of MAPK/ERK
      kinase MEK), irbesartan (an AT-1 receptor blocker), and N-acetylcysteine (NAC, an
      antioxidant), angiotensin-converting enzyme inhibitor (ACEI), or tumor necrosis
      factor alpha (TNFalpha) prior to exposure to AngII or Aldo for 0.5 h, 1 h, 2 h,
      and 4 h respectively. The binding activities of NF-kappaB DNA were observed by
      EMSA. The expression of IkappaBalpha protein was detected with Western blotting.
      Histochemistry was used to detect the expression of NF-kappaB p65. RT-PCR was
      used to detect the expression of TNFalpha mRNA in HSC-T6 cells. RESULTS: The
      binding activity to NF-kappaB of the liver tissues was the strongest in the Mo
      group, followed by the Pe and Lo groups and Nc group. The IkappaBalpha
      expressions in liver tissues 4 and 6 weeks after the beginning of experiment in
      the Pe and Lo groups were significantly stronger than that in the Mo group (both
      P < 0.05). 0.5 hour after the intervention of AngII the DNA binding activity of
      the HSCs began to increase and peaked 1 hour later and then gradually decreased.
      The increase of NF-kappaB activity induced by AngII could be inhibited by
      irbesartan, ACEI and NAC pretreatment and could not be inhibited by U0126
      pretreatment. Combined action of AngII and TNFalpha significantly increased the
      NF-kappaB DNA binding activity. The IkappaBalpha expression began to decrease 0.5
      hour after the intervention of AngII and reached the lowest value 2 hours after.
      The expression of IkappaBalpha protein was increased by ACEI (P < 0.05),
      irbesartan and NAC (both P < 0.01). EMSA showed that 0.5 hour after the
      intervention of Aldo the DNA binding activity began to be increased and peaked by
      1 hour and then began to be decreased. NAC, but not U0126 partly inhibited the
      increased of NF-kappaB activity induced by Aldo. Combined action of Aldo and
      TNFalpha significantly increased the NF-kappaB activity. Aldo increased the
      expression of IkappaBalpha protein in the HSCs at different time points (all P <
      0.05). 0.5 hour after the AngII intervention the IkappaBalpha protein expression
      began to decrease and reach the lowest value 1 hour later and then began to
      increase 2 hours later. the IkappaBalpha protein expression was significantly
      decreased in the NAC and NAC+ Aldo intervention groups (both P < 0.05). There was
      no significant difference in IkappaBalpha protein expression between the Aldo
      intervention group and U0126 + Aldo, TNFalpha, and Aldo + TNFalpha treatment
      groups (all P > 0.05). Before stimulation, NF-kappaB was expressed in the plasma
      of HSCs, however, after the stimulation of AngII or Aldo for 1 hour it was
      expressed in the nuclei, and then transferred from the nuclei to the plasma 4
      hours after the stimulation. However, little nuclear transfer was observed after
      pretreatment of NAC followed by AngII or Aldo intervention. The TNFalpha mRNA
      expression was significantly increased in the AngII and Aldo treatment groups in
      comparison with the control group (both P < 0.05). The TNFalpha mRNA expression
      was significantly weaker in the irbesartan + AngII, NAC + AngII, and ACEI groups
      in comparison with the AngII group (all P < 0.05). CONCLUSION: Stimulation of NF
      kappaB activity mediates hepatic fibrosis induced by intrahepatic renin
      angiotensin-aldosterone system (RAAS).

PMID- 15854526
TI  - [Expression of mucin 1 and tumor invasiveness in breast carcinoma].
AB  - OBJECTIVE: To study the relationship of abnormal expression of mucin 1 with the
      invasiveness of breast carcinoma cells. METHODS: Immunohistochemistry was used to
      detect the protein expression of mucin 1 in 5 specimens of juxta-cancerous normal
      tissues, 20 specimens of benign breast tumors, 35 specimens of early breast
      carcinoma, 22 specimens of infiltrating cancerous tissues, and 20 specimens of
      lymph node foci with metastatic breast carcinoma. Human breast cancer cells of
      the line MCF-7 were cultured and transfected with antisense oligodeoxynucleotide
      (ASODN) of mucin 1. The mucin 1 mRNA expression in the cells was detected by RT
      PCR and the protein expression of mucin 1 in the cells was detected by flow
      cytometry. The cell invasiveness was detected by Matrigel invasion assays.
      RESULTS: Top membrane positive expression of mucin 1 was observed in the normal
      breast tissues and breast benign tumors and whole membrane positive expression of
      mucin 1 was observed in the 30 of the 35 specimens of early breast carcinoma, 18
      of the 22 specimens of breast infiltrating carcinoma, and 17 of the 20 specimens
      of lymph node metastatic tissues. The mRNA and protein expressions of mucin 1 in
      the breast carcinoma cells treated with ASODN of mucin 1 were significantly
      decreased (both P < 0.05). The number of invasive cells decreased significantly
      in the cell treated with ASODN of mucin 1 in comparison with those treated with
      sense nucleotide (P < 0.05). CONCLUSION: The abnormal distribution of mucin 1
      contributes to the invasiveness of carcinoma cells and may not make difference in
      the lymphogenous metastasis of the carcinoma. The invasiveness of breast
      carcinoma cells can be inhibited by the ASODN complementary to the start site of
      mucin1 mRNA.

PMID- 15854527
TI  - [Screening of differential expression genes between primary breast cancer and its
      lymph node metastasis using single primer amplification of cDNA for microarray].
AB  - OBJECTIVE: To screen genes related to breast cancer metastasis by comparing
      difference of expression profile between primary breast cancer and its lymph node
      metastasis. METHODS: The cell total RNA was extracted from 10 breast cancer
      specimens, including the primary cancer and metastatic cancer tissues of axillary
      lymph nodes resected during operation. Single primer amplification (SPA) was used
      to prepare fluorescence-labeled targets and then Oligo microarray concluding 21
      000 human functional genes was used to screen out 1.5 fold or more differential
      expression genes in at least 5 pairs of samples. The screened-out genes were
      identified by real-time PCR. RESULTS: Preparing targets by using SPA reduced the
      initial RNA to 0.25 microg, with 57 genes screened out, the expression of 19 of
      which were up-regulated and the expression of 38 of which were down-regulated in
      the metastatic tissues. Eight differentially expressed genes were related to cell
      migration and adhesion, 14 to signal transduction, and 14 to cell growth or
      metabolism. Real-time PCR showed that the fibronectin (FN) mRNA expression in the
      lymph node metastasis was only 1/3.6 of that in the matched primary breast cancer
      in 30 cases (t = -3.188, P = 0.003). CONCLUSION: SPA is a sensitive method for
      preparing targets. Genes related to cell migration and adhesion, signal
      transduction, and cell growth or metabolism, which are associated with the
      biology process of metastasis have been screened out. FN as a potent marker may
      contribute to diagnosis of metastasis and prognosis for breast cancer patients.

PMID- 15854528
TI  - [Association between Helicobacter infection in liver tissue and primary liver
      carcinoma].
AB  - OBJECTIVE: To investigate the relationship between Helicobacter species and
      primary liver carcinoma (PLC). METHODS: The liver samples resected during
      operation from 21 patients with PLC diagnosed by histopathology and 12 patients
      with other liver diseases as controls were studied. Helicobacter species in liver
      specimens from the studied subjects were examined by PCR with Helicobacter
      specific 16SrRNA primers. The amplified products were identified by Southern
      hybridization and nucleic acid hybridization in situ and sequencing. The
      specimens were made slices to undergo in situ hybridization of cDNA-mRNA of
      Helicobacter. Qualitative and quantitative studies were used to assess the
      correlation of liver tissue helicobacter infection with PLC. RESULTS: Thirteen of
      the 21 samples (62%) of PLC were positive for Helicobacter specific 16SrRNA gene,
      while none was positive in the controls (P < 0.01). In situ hybridization results
      demonstrated a highly Helicobacter 16SrRNA-mRNA positive rate in the PLC group
      (62%) and none of positive specimen in the control group (P < 0.01). Nine of the
      Helicobacter specific PCR applicants were sequenced and a homology of 97.80% in
      comparison with 16SrRNA of H p was found. CONCLUSION: Helicobacter infection may
      exist in the liver tissues of PLC patients with a high infection rate, suggesting
      an association between Helicobacter infection and PLC.

PMID- 15854530
TI  - [Effects of leptin and insulin on leptin receptors mRNA expression in human
      hepatocellular HepG2 cells].
AB  - OBJECTIVE: To study the leptin receptor isoforms regulation by leptin and
      insulin. METHODS: Human hepatocellular carcinoma cells of the line HepG2 were
      cultured in DMEM containing 10% FBS in six-well plate and were incubated for 24
      hours in serum-free medium containing 0, 10(-9), 10(-8), 10(-7), and 10(-6) mol/L
      of human leptin or insulin. Using the semi-quantitative RT-PCR technique, the
      mRNA expressions of long (OB-Rb) and short (OB-Ra: OB-R219.3) leptin receptor
      isoforms were measured. RESULTS: OB-Rb and OB-R219.3 mRNAs were expressed in this
      cell line. Leptin of the concentrations of 10(-7) approximately 10(-6) mol/L
      significantly inhibited the OB-Rb mRNA expression, with the maximum decrease (by
      43%) at the concentration of 10(-6) mol/L. Similarly the mRNA expression of OB
      R219.3 was also markedly reduced in cells treated with leptin of the
      concentrations of 10(-8) approximately 10(-6) (mol/L), with the maximum
      inhibition (by 49%) at the concentrations of 10(-6) mol/L. Insulin showed no
      effect on OB-Rb and OB-R219.3 mRNAs expression in HepG2 cell. CONCLUSION: In
      HepG2 cells, leptin down-regulates the expressions of OB-Rb and OB-R219.3 mRNAs,
      and insulin has no effect on OB-Rb and OB-R219.3 mRNAs, which contributes at
      least partly to an understanding of the mechanism of leptin resistance in vivo
      and suggests that leptin-induced receptor down-regulation may be relevant to
      leptin resistance at sites of peripheral action.

PMID- 15854531
TI  - [Detection of integration status of human papillomavirus 16 in cervical
      precancerous lesions].
AB  - OBJECTIVE: To investigate the prevalence of integration of human papillomavirus
      16 (HPV16) DNA into the host genome in cervical squamous intraepithelial lesions
      (SIL). METHODS: Multiplex PCR was used to detect the HPV/HPV16 infection and
      integration status of HPV16 in the surplus cells from liquid-based cytological
      samples from 108 patients with cervical cancer precursor lesions. Consensus
      primers GP5+/GP6+ were used to amplify a 150 bp long fragment in the conserved
      region of the HPV L1 gene so as to detect the presence pf HPV. Scion Image 4.0
      electrophoresis image analysis soft was used to calculate the E2/E6 ratio so as
      to evaluate the episomal and integrated status of HPV16 infection: in episomal
      form, both targets should be equivalent, and in integrated form, E2 gene would be
      absent, while in mixed form of episomal/integrated mixed form, the copy number of
      E2 would be less than that of E6. RESULTS: Sixty-two out of the 108 patients
      (57.41%) had HPV infection. HPV16 were found in 32 of the 108 samples (29.63%).
      Among the 32 cases HPV16 DNA was exclusively episomal in 15 cases (46.88%),
      concomitant in 13 cases (40.62%), and integrated in 4 cases (12.50%). The
      prevalence of integrated and/or concomitant forms of HPV-16 DNA increased with
      progression of cervical disease. The prevalence of integrated form was 54.55% in
      the patients of CIN3 type, 50.00% in CIN2 type, 28.07% in CIN1 type, and 11.54%
      in the inflammatory type with significant differences between any 2 groups (all P
      < 0.01). CONCLUSIONS: HPV16 integration into the host genome is already present
      in some of CIN lesions. The multiplex PCR estimation of the HPV L1, HPV16 E2, E6
      genes and E2/E6 ratio could be a simple method for detecting HPV/HPV16 infection
      and its integration status in liquid-based residual samples. It would be a
      helpful complementary tool for cytological screening to identify those patients
      at high risk of developing high-grade squamous intraepithelial lesions and
      cervical cancer.

PMID- 15854532
TI  - [Regulation of AAV-mediated glial cell-line derived neurotrophic factor
      expression by using improved Tet-on trans-activator].
AB  - OBJECTIVE: To control the expression of AAV-mediated glial cell-line derived
      neurotrophic factor (GDNF) gene purposely by incorporating novel Tet-On trans
      activator rtTA2s-S2, which prevents potential harms caused by over-expression of
      recombinant target genes. METHODS: Oligonucleotide with specific monocloning
      sites was inserted into the hHG part of pAAV-GDNFflag. Trans-activator from
      pUHrT61-rtTA2s-S2 and TRE from pTRE-d2EGFP were amplified by PCR and inserted
      into pCRII-TOPO respectively. Possible mutation was eliminated by sequencing. TRE
      and rtTA2s-S2 were then inserted into the oligonucleotide of pAAV-GDNFflag to
      form pAAV-rtTA2s-S2-TRE-GDNFflag. pAAV-rtTA2s-S2-TRE-d2EGFP was constructed by
      replacing the GDNFflag part with d2EGFP. The plasmids were digested by Xba I and
      compared with theoretic values. HEK 293 cells were cultured and co-transfected
      with pAAV-GDNFflag and helper plasmids pHLP19 and pAdeno5 so as to complete the
      package of recombinant adeno-associated virus (rAAV) Crude virus lysate was
      purified by two-sequential continuous CsCl gradient ultracentrifugation, dialyzed
      and condensed by millipore filter. The titer of rAAV was determined by real-time
      quantitative PCR. Another HEK293 cells were cultured, transfected with rAVV, and
      then cultured in 2 kinds of culture fluid: with or without doxycyclin (Dox).
      Fluorescence microscopy was used to calculate the percentage of fluorescent cells
      so as to detect AAV-rtTA2s-S2-TRE-d2EGFP, and Western blotting was used to detect
      the GDNF protein in the lysate of the HEK293 cells, thus testifying the
      regulatory function in vitro of rtTA2s-S2. Twenty male Wistar mice were randomly
      divided into 2 groups: experiment group, fed with Dox and sucrose (Dox-positive
      group), and control group, fed with only sucrose (Dox-negative group). Two days
      after AAV-rtTA2s-S2-TRE-GDNF was injected into the gastrocnemius muscles of the
      mice. Two weeks the mice were killed and their gastrocnemius muscles were taken
      out. ELISA was used to examine the content of GDNF in the homogenate of
      gastrocnemius muscle so as to examine the regulatory effect of rtTA2s-S2 in vivo.
      RESULTS: Tests showed that the recombinant plasmids were constructed correctly.
      The fluorescent cell positive rate in the Dox-positive culture fluid of HEK293
      cells was 52.4%, significantly higher than that in the Dox-negate culture fluid
      (7.2%, P < 0.01). Western blotting of the HEK 293 cell lysate showed clear band
      of GDNF in the Dox-positive group and failed to show visible band in the Dox
      negative group. The content of GDNF in the homogenate of gastrocnemius muscles of
      the Dox-positive group was 32.6pg/ml +/- 2.6 pg/ml, significantly higher than
      that of the Dox-negative group (10.1 pg/ml +/- 2.4 pg/ml, P < 0.01). CONCLUSION:
      Novel Tet-on trans-activator rtTA2s-S2 regulates downstream AAV-mediated GDNF
      expression in a stringent manner and does not impair AAV infecting efficiency
      when constructed together with TRE and GDNF within one AAV vector.

PMID- 15854533
TI  - [Therapeutic effects of RNA interference targeting HIF-1 alpha gene on human
      osteosarcoma].
AB  - OBJECTIVE: To investigate the inhibition effect of the small hairpin RNA (shRNA)
      targeting HIF-1alpha gene on the growth of osteosarcoma in vitro and in vivo.
      METHODS: The small hairpin RNA (shRNA) eukaryotic expression vector targeting HIF
      1alpha gene, named pSilencer-HIF, was constructed and transfected into cultured
      human osteosarcoma cell of line SaOS-2 via liposome reagent. Then the
      osteosarcoma cells were cultured under chemical hypoxia conditions. The
      inhibition effects on HIF-1alpha gene were determined by semi-quantitative
      reverse transcription PCR and Western blot analysis. The in vitro cellular growth
      activities were assayed by MTT colorimetry. The cell apoptosis was studied by
      electron microscopy, TUNEL assay, and annexin V/PI double staining. Eighteen
      Balb/C mice were randomly divided into 3 equal groups to be inoculated with SaOS
      2/shRNA, SaOS-2/neo (blank vector), or SaOS-2 subcutaneously respectively and
      then the appearance and size of tumors were observed. Four weeks later the mice
      were killed and the volumes of tumor were calculated so as to evaluate the
      therapeutic effects of shRNA. RESULTS: The successful construction of pSilencer
      HIF plasmid was identified with sequencing. After the shRNA expression vector was
      transfected into the SaOS-2 cells, the expression of HIF-1alpha gene was
      inhibited significantly (by 90%). The cellular growth activities in the SaOS-2
      cells transfected with pSilencer-HIF plasmid decreased obviously in hypoxia
      culture. After 72 hours of exposure to hypoxia, electron microscopy and TUNEL
      assay showed classic apoptosis characters in the SaOS-2 cells transfected with
      pSilencer-HIF plasmid with an apoptosis rate of 18.71% +/- 0.98%, significantly
      higher than those in the negative control group transfected with pSilencer-neo
      and in the nontransfected group (both P < 0.01). The growth speed and formation
      rate of xenograft tumor in pSilencer-HIF transfected mice slowed down
      significantly. A lot of necrotic tissues could be observed in the pSilencer-HIF
      transfected group by HE staining, however, there was no similar inhibitive effect
      in the control groups. CONCLUSION: shRNA targeting HIF-1alpha gene blocks the
      hypoxia transduction pathway efficiently and inhibits the growth of osteosarcoma
      cells.

PMID- 15854534
TI  - [Effect of transforming growth factor beta1 on cellular biological behavior in
      primary and recurrence ovarian cancer].

PMID- 15854535
TI  - [Effects of carvedilol on the expression of IL-1beta and collagen precipitation
      in myocardium in post-myocardial infarction rats ].

PMID- 15854536
TI  - [Comparative study of effects of fluvastatin and losartan on left ventricular
      remodeling in rat myocardial infarction].

PMID- 15854537
TI  - [Heparin in the treatment of severe intrahepatic cholestasis of pregnancy].

PMID- 15854538
TI  - [Drug allergy induced salivary and lacrimal diseases: clinical analysis of 25
      cases ].

PMID- 15854539
TI  - [Medical ethics: unavoidable issue in medical research].

PMID- 15854540
TI  - [Basic research of atherosclerosis].

PMID- 15854541
TI  - [Rituximab monoclonal antibody in the treatment of retractable idiopathic
      thrombocytopenic purpura--a case report].

PMID- 15854543
TI  - [Hemopoietic stem cell transplantation: say farewell to few donors].

PMID- 15854542
TI  - [Can acute leukemia be cured?].

PMID- 15854544
TI  - [New targets for molecular therapy of acute leukemia: a "single-hit" or "multiple
      hit" strategy against signaling pathway].

PMID- 15854545
TI  - [Arsenic treatment for leukemia: new model of human cancer target treatment].

PMID- 15854546
TI  - [Monoclonal antibody therapy targeting surface antigens of leukemic cells].

PMID- 15854547
TI  - [Significance of dynamic detection of WT1 expression on monitoring minimal
      residual disease in leukemia patients following allogeneic bone marrow
      transplantation].
AB  - OBJECTIVE: To investigate the significance of monitoring Wilms' tumor gene (WT1)
      expression level in bone marrow of leukemia patients following allogeneic bone
      marrow transplantation (allo-BMT). METHODS: Real-time quantitative reverse
      transcription polymerase chain reaction method was established for measuring WT1
      and GAPDH expression levels in bone marrow cells of 15 patients with leukemia,
      including a total of 111 specimens during the follow-up, and in 23 non-leukemia
      patients by using LightCycler. Normalized WT1 expression level (WT1(N)) was
      determined as a ratio of WT1 to GAPDH times 10(4). RESULTS: The median expression
      levels of WT1(N) in 17 samples of newly diagnosed patients, 6 samples of relapsed
      patients, 88 samples from leukemia patient in complete remission and 23 samples
      of non-leukemic controls were 40.18 (5.48 to 510.27), 125.89 (34.50 to 273.95),
      4.80 (0 to 56.96) and 1.47 (0 to 8.56) respectively. Nonparameter statistic
      analysis (Mann-Whitney U test) showed that the WT1(N) expression levels in the
      newly diagnosed group and relapsed group were statistically higher than in those
      in the complete remission group and non-leukemic controls (all P < 0.01), without
      significant differences between the complete remission group and control group (P
      = 0.692) and between the newly diagnosed group and relapsed group (P = 0.595). In
      general, the dynamic curves of WT1(N) levels following allo-BMT were consistent
      with the tendency of changes in expression levels of corresponding fusion genes
      for minimal residual disease (MRD) monitoring. Spearman Rho correlation analysis
      revealed that the correlation coefficient between the WT1(N) expression levels
      and BCR/ABL, AML/ETO, PML/RARalpha and MLL/AF17 fusion genes expression were
      0.678 (P = 0.00), 0.677 (P = 0.00), 0.806 (P = 0.00) and 0.553 (P = 0.049)
      respectively. Three patients relapsed after allo-BMT and one patient relapsed
      before allo-BMT during the follow-up. A re-increment of WT1(N) expression level
      during follow-up could be detected 40 to 180 days earlier to hematological
      relapse. CONCLUSION: The WT1 expression level of leukemia patients following allo
      BMT measured by real time RT-PCR can be a useful tool for monitoring MRD and
      warning the clinical relapse during follow-up.

PMID- 15854548
TI  - [The activation of JAK/STAT signal pathway in hypereosinophilic syndrome and the
      patients therapeutic response to imatinib].
AB  - OBJECTIVE: To determine whether JAK/STAT pathway is involved in proliferation of
      hypereosinophilic syndrome (HES) cells, and reveal the pathogenesis of HES;
      observe the dynamic change of the clinical phenotype and hematological response,
      the expression of janaus kinase/signal transducer and activator of transcription
      (JAK/STAT) protein or FIP1L1-PDGFRA mRNA in one HES patient treated with low-dose
      imatinib. METHODS: The granulocytes of peripheral blood of 4 HES patients,
      including 3 FIP1L1-PDGFRA positive cases and 1 negative case, were collected. The
      expression of JAK2, STAT3, and phosphorylated STAT (P-STAT5) proteins were
      detected by western blotting. One FIP1L1-PDGFRA fusion gene positive patient was
      administered with low-dose imatinib. Retrospective reverse transcription
      polymerase chain reaction (RT-PCR) analysis of FIP1L1-PDGFRA was performed and
      the expressions of JAK2, STAT3 and P-STAT5 were detected by western blotting
      before treatment and 10, 30, and 60 days after the beginning of treatment.
      RESULTS: Upregulation of JAK2, STAT3, and P-STAT5 proteins was shown in 3 FIP1L1
      PDGFRA fusion gene positive HES patients, while all of these proteins were not
      expressed in one case of FIP1L1-PDGFRA negative HES. Continuous hematological
      remission was observed in one FIP1L1-PDGFRA fusion gene positive HES patient
      after low-dose imatinib treatment. The amount of FIP1L1-PDGFRA transcripts in
      peripheral blood granulocytes was significantly decreased in 30 days after
      therapy and turned negative 60 days after therapy. JAK2, STAT3, STAT5, and P
      STAT5 expressions were all down-regulated time-dependently and were all negative
      60 days after. CONCLUSION: There is excessive activation of JAK/STAT signal
      pathway in HES patient, which may contribute to the malignant proliferation of
      eosinophils. Low-dose imatinib, that induces complete hematological and molecular
      genetic remission, exerts significant effects on FIP1L1-PDGFRA positive HES.

PMID- 15854550
TI  - [Detection and quantification of BCR-ABL transcripts in patients with chronic
      myeloid leukemia by real-time quantitative reverse transcriptase polymerase chain
      reaction].
AB  - OBJECTIVE: To investigate the effect of real-time quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR) approach in chronic myeloid
      leukemia (CML) for detecting the minimal residual disease (MRD) or monitoring the
      treatment response and predicting the prognosis. METHODS: Fifty-six CML patients,
      39 males and 17 females, aged 39 (16 approximately 66), with disease history and
      frozen RNA specimens were studied, 31 of which were in the incipient chronic
      phase, 7 in the accelerated phase, and 17 in the rapidly progressing phase. Three
      or more frozen RNA specimens collected before and after treatment were preserved
      in 11 of the patients. Breakpoint cluster region-Abelson murine leukemia viral
      oncogene (BCR-ABL) of the patients in different CML stages was analyzed by RT-PCR
      approach. RESULTS: The BCR-ABL transcript of those patients remaining in chronic
      period after treatment decreased to 1/3 that of the baseline level six months
      after the initiation of treatment and then remained at that level. The BCR-ABL
      transcript of those in which progressing change occurred increased when such
      change occurred. After allogeneic transplantation of peripheral blood stem cells
      the BCR-ABL level decreased significantly. The median DoseN in the 17 progressing
      patients was 10 492, significantly higher than those of the 31 patients in
      chronic phase (5920) and in the 7 patients in accelerated phase (4444, both P <
      0.05). The minimal residual disease and the treatment response were closely
      associated with the level and its variation of BCR-ABL transcripts, the
      transcripts level in blastic crisis was significantly higher than that in chronic
      phase or accelerated phase. CONCLUSION: Real-time quantitative RT-PCR is reliable
      and can be used to detect the minimal residual disease, monitor the treatment
      outcome, and predicting blastic crisis.

PMID- 15854551
TI  - [Cardiovascular disease in Chinese chronic renal insufficiency patients
      epidemiology survey].
AB  - OBJECTIVE: Cardiovascular (CV) disease (CVD) is the single most important cause
      of death among Chinese dialysis patients, accounting for 51% of overall
      mortality. The study was performed to investigate the prevalence and the spectrum
      of CVD in Chinese chronic kidney disease (CKD) patients. METHODS: The multicenter
      Chinese cohort study examined 1239 CKD patients from 7 main medical centers
      (distributed in 5 regions of China) who were hospitalized between 2002 and 2003.
      RESULTS: (1) The most prevalent pathological form of CVD was left ventricular
      (LV) hypertrophy (LVH), accounting for 58.5% of total patients. The prevalence of
      coronary artery disease (CAD), congestive heart failure (CHF), and
      cerebrovascular accidents (CVA) was 16.5%, 27.7% and 5.6%, separately. (2) The
      cohort with minor renal dysfunction (stage 2-3) had higher prevalence of CAD
      (5.9%) and CVA (1.0%) compared with general population in the same regions. Up to
      41.2% of minor CKD patients were complicated with LVH, and 13.8% of them had
      clinical evidence of CHF. The prevalence of CAD, LVH and CHF increased as
      glomerular filtration decline. (3) The prevalence of CAD (20.0%) was much lower
      and the prevalence of CVA (5.4%) was higher in Chinese dialysis patients than
      that in American dialysis population. There was significant geographical
      variations in CAD prevalence, but it was not different between genders.
      CONCLUSION: The CV risk is significantly increased in patients with CKD. Even
      minor CKD has a major impact on the CV risk. The prevalence of CAD in Chinese
      dialysis patients is markedly lower than that in American dialysis population.

PMID- 15854552
TI  - [Amniotic fluid: a novel source for tissue engineering].
AB  - OBJECTIVE: To investigate the possibility of using amniotic fluid cells as seed
      cells for tissue engineering. METHODS: Amniotic fluid was obtained by ultrasound
      guided amniocentesis performed on pregnant women with a gestational age ranging
      from 16(th) approximately 23(rd) weeks. The cells isolated from the amniotic
      fluid were cultured in F10 culture fluid with 10% FBS. Immunocytochemistry was
      used to examine the standard intermediate filaments. After 3 passages of
      subculture, the cells were harvested and seeded onto PGA polymer scaffold. The
      cellular morphology, structure and adhesion with scaffold were evaluated by
      contrast microscope and scanning electronic microscope. RESULTS: The amniocytes
      expanded rapidly in culture media. Immunocytochemistry revealed positive signals
      for vimentin, smooth muscle action (SMA), and pan cytokeratin, and negative
      signals for desmin. Amniocytes-polymer complex analysis showed confluent cells
      firmly attached to the scaffold, with no evidence of cell death. CONCLUSION: The
      expansion potential of amniotic fluid cells is active. They express the
      characteristics of mesenchymal cells. The cells on PGA polymer scaffold can grow
      rapidly and maintain its morphological property. So the amniotic fluid may be a
      practical cell source for tissue engineering.

PMID- 15854553
TI  - [hTERT promoter regulated replication-selective adenovirus CNHK300 in treatment
      of hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the therapeutic efficiency of replicative adenovirus
      CNHK300 targeted at telomerase-positive hepatocellular carcinoma. METHODS: Human
      liver cancer cell line HepGII and Hep3B, human embryonic kidney cell line 293,
      and normal human fibroblasts of the line BJ were cultured and added with
      adenoviruses CNHK300, ONYX-015 (55 000 protein deleted adenovirus), or wtAd5
      (wild type 5) with different multiplicity of infection (MOI) for 7 days. 293
      cells were used to measure the titer of the filial generation virus from
      different cells. The cell survival rate was calculated by MTT method 2, 4, 6, and
      8 days after. Different cells were added with CNHK300 virus and then the E1A
      protein in the cytoplasm was measured by western blotting. Fluorescence
      microscopy was used to observe the CNHK300-EGFP proliferation after the cells
      were cultured and added with the virus for 1.5 hours. RESULTS: The replicative
      viruses CNHK300 and wtAd5 proliferated rapidly in HepGII and Hep3B cells since 24
      hours after inoculation and proliferated 40625 and 65326 times respectively with
      a proliferation potential similar to that of the wild-type adenovirus and much
      higher than that of the ONYX-015 virus. CNHK300 of the MOI of 0.0002 killed half
      of the cancer cells, especially those of the line Hep3B, within 5 approximately 6
      days, and CNHK300 virus of the MOI of 0.5 pfu/cell killed almost all the HepGII
      cells in the 8th day, with a killing power lower than that of the wild-type virus
      and higher than that of the ONYX-015 cells. The IC(50) was as low as MOI of 0.002
      pfu/cell for the Hep3B cell and was as high as MOI of 100 pfu/cell for the BJ
      cell. CNHK300 was a less powerful killer of fibroblasts than wild-type virus. E1A
      expression was shown by western blotting in 293 cells and CNHK300-infected liver
      cancer cells, but not in the CNHK300-infected normal human fibroblasts.
      Fluorescence microscopy showed only isolated fluorescence-positive fibroblasts
      till the 10th day of infection, but obvious proliferation of CNHK300-EGFP virus
      since the 3rd day and fluorescence-positive cells in sheets by the 7th day,
      however, the fluorescent intensity was weakened since the 10th day. CONCLUSION:
      Tumor-selective adenovirus CNHK300 replicates in telomerase-positive liver cancer
      cells efficiently as well as wtAd5 and causes oncolysis, but has severely
      attenuated proliferation and cytolysis in normal cells.

PMID- 15854555
TI  - [Study on p53 tetramerization domain in improving functional affinity and
      biological activity of antibody].
AB  - OBJECTIVE: To fuse the genes of p53 tetramerization domain and anti-CD3/anti
      prostate-cancer bispecific single-chain antibody (BsAb), and exploit a new way to
      improve the functional affinity and biological activity of antibody. METHODS:
      Genes of p53 tetramerization domain and anti-CD3/anti-prostate-cancer BsAb was
      fused by technique of DNA sub-cloning. The fusion gene confirmed by sequencing
      was subcloned into the pSectag2-B plasmid. Then the recombinant plasmid was
      transfected into HeLa cells. The expression products, which were analyzed by both
      SDS-PAGE and western blotting, were purified with Ni(2+)-NTA superflow affinity
      chromatography. mBsAb-pSectag2-B plasmid was added into the suspensions of human
      peripheral blood mononuclear cells (PBMCs) and PC-3 cells respectively. Flow
      cytometry was used to examine the binding rate of multivalent anti-prostate
      cander/anti-CD3 bispecific scFv with PBMCs and PC-3 cells. T cells were isolated
      from the PBMCs. PC-3 cells were labeled with Na(2)[(51)Cr]O(4) used as target
      cells. Labeled PC-3 cells, T cells, and different concentrations of mBsAb were
      mixed. Natural release control well with labeled target cells only and maximum
      release control well with labeled target cells and 10% SDS were prepared. The
      supernatants were extracted. gamma calculator was used to calculate the counts
      per minute (cpm) values to calculate the specific release rate of (51)Cr.
      RESULTS: Sequencing showed a fragment from mBsAb-pSectag2-B with the size of 1.7
      kb corresponding to the predicted value. SDS-PAGE and Western blotting showed
      expression of 67 000 D protein in the supernatant of culture fluid of HeLa cells
      transfected with MBsAb-pSectag2-B plasmid. The binding rates of multivalent anti
      prostate-cancer/anti-CD3 bispecific scFv with PBMC and PC-3 cells were 70.4% and
      81% respectively, significantly higher than those of anti-prostate-cancer/anti
      CD3 bispecific scFv. In the presence of mBsAb the activated T cells lysed PC-3
      cells in positive correlation with the antibody concentration and effective
      cell/target cell ratio and with a lysis rate significantly higher than those of
      the control groups. CONCLUSION: Multivalent anti-CD3 x anti-prostate-cancer BsAb
      exhibits much higher functional affinity and biological activity than anti-CD3 x
      anti-prostate-cancer BsAb, which may break a new path to the improvement of
      functional affinity and biological activity of antibody.

PMID- 15854554
TI  - [Promotion of the survival of ischemic skin flap by transplanted endothelial
      progenitor cells transfected with VEGF165 gene: an experimental study with mice].
AB  - OBJECTIVE: To investigate the feasibility of transplanted endothelial progenitor
      cells transfected with VEGF165 gene to ischemic flap with increased
      neovascularization and augmented the survival areas. METHODS: EPCs were isolated
      from human cord blood and cultured in vitro. Plasmid PcDNA3.1(-)/VEGF165
      containing VEGF gene was transfected into the EPCs. EPCs transfected with blank
      plasmid, and EPCs without transfection were used as controls. ELISA was used to
      detect the expression of VEGF protein in the culture fluids. The EPCs were dyed
      with CM-DiI 7 days later. Ischemic skin flaps were made on the backs of 27 nude
      mice. The mice were randomly divided into 3 equal groups with their skin flaps
      being transplanted with EPCs transfected with 3.1(-)/VEGF165 plasmid, EPCs not
      transfected with 3.1(-)/VEGF165 plasmid, and injected with M199 medium at the
      basal part. Four days after the peduncles of the skin flaps were cut. Seven days
      after the cutting-off of the peduncles the survival rate of skin flap was
      observed and the blood perfusion was observed with laser Doppler flowmetry, 10
      days after the density of capillary arteries were observed with microcirculation
      microscope. Three specimens of skin flap were taken 7 and 11 days after the skin
      flaps were made to undergo histological examination to detect the density of
      capillary arteries by CD34 immunohistochemistry and to observe the proliferation
      of EPCs with fluorescence microscopy. Peripheral blood samples were collected 1,
      4, 7, 14, and 28 days after the skin flaps were made to undergo ELISA to detect
      the levels of VEGF protein RESULTS: The VEGF levels in the culture supernatants
      of the groups A, B, and C were 352 ng/L +/- 35 ng/L, 45 ng/L +/- 5 ng/L, and 0
      ng/L respectively with significant difference between any 2 groups (all P <
      0.05). The skin flap survival rates of the three groups were 97.2%, 60.3%, and
      34.2% respectively with significant difference between any 2 groups (all P <
      0.05) and the survival quality of the group A was the best. The capillary density
      of the group A was greater than those of the groups B and C. The VEGF levels at
      any time point of the group A were all significantly higher than those of the
      group B and C (all P < 0.05) and there was not a significant difference between
      the groups B and C. The capillary density levels at different time points
      decreased progressively in the order of groups A, B, and C with significant
      difference between any 2 groups (all P < 0.05). No EPC was shown by fluorescence
      microscopy in the skin flaps of the group C. The EPC density in skin flap 7 and
      11 days after the flaps were made were 136 +/- 10 and 75 +/- 6/mm(2) and 305 +/-
      26 and 199 +/- 18/mm(2) respectively with significant differences between the
      groups A and B. (both P < 0.05). CONCLUSION: The EPCs from human cord blood,
      especially those transfected with VEGF165 gene increases the neovascularization
      in ischemic skin flaps and augments their survival rate.

PMID- 15854557
TI  - [Oligonucleotide microarrays in the screening of differentially expressed genes
      in skin of rat fetus in early and late pregnancy ].

PMID- 15854556
TI  - [Heat-shock protein 70 may be a putative endogenous ligand of Toll-like receptor
      4 of human monocytes].
AB  - OBJECTIVE: To explore the relation between human heat shock protein 70 (HSP70)
      and Toll-like receptor-4 (TLR4) in human monocytes. METHODS: Periphery blood
      mononuclear cells were isolated from the samples of healthy blood donors' whole
      blood and monocytes were prepared and cultured. HSP70 of the final concentrations
      of 2.5 microg/ml, 5.0 microg/ml, 7.5 microg/ml, and 10 microg/ml respectively was
      added; 6 hours later the concentration of TNF-alpha in the supernatant was
      detected. Another monocytes were cultured and HSP70 of the final concentration of
      5.0 microg/ml was added and the concentrations of NF-kappaB were detected 0, 30,
      60, and 120 minutes later respectively. TLR4 blocker of the final concentrations
      of 5 microg/ml, 20 microg/ml, and 30 microg/ml respectively was added into
      another culture for 30 minutes and 5.0 microg/ml HSP70 was added, then
      immunochemistry was used to detect the concentration of NF-kappaB 120 minutes
      after ELISA was used to detect the concentration of and TNF-alpha 8 hours later.
      In order to examine the influence of HSP70 on the TLR4 in the cytomembrane of
      monocytes, HSP70 of the final concentration of 5.0 microg/ml was added into the
      culture of monocytes for 0, 30, 60, and 120 minutes respectively then flow
      cytometry was used to detect the mean fluorescence intensity (MFI) of TLR4.
      RESULTS: HSP70 stimulation increased the TNF-a concentration in the supernatant
      dose-dependently. The percentages of NF-kappaB positive monocytes were 38 +/- 6,
      67 +/- 12, and 54 +/- 12 30 min, 60 min, 120 min after HSP70 stimulation, all
      significantly higher than that at the beginning of experiment (17 +/- 6, P <
      0.05, P < 0.01, and P < 0.01). The percentages of NF-kappaB positive monocytes
      were 39% +/- 4%, 32% +/- 6%, and 28% +/- 6% 120 minutes after anti-TLR4 mAb
      stimulation, all significantly lower than that of the control group (67% +/- 12%,
      all P < 0.05). TLR4 blocker of different concentrations significantly inhibited
      the TNF-alpha secretion by the monocytes (all P < 0.05). The MFI of TLR4 in the
      cytomembrane of monocyte was significantly down-regulated 60 minutes, especially
      120 minutes, after the HSP70 stimulation in comparison with that before the
      stimulation (P < 0.05 and P < 0.01). CONCLUSION: TLR4 appears to be involved in
      HSP70-mediated activation of innate immunity.

PMID- 15854558
TI  - [Comparative study of different diagnostic criteria of metabolic syndrome].

PMID- 15854559
TI  - [Acute deep vein thrombosis of lower limbs treated by thrombolytic therapy with
      recombinant tissue-type plasminogen activator].

PMID- 15854560
TI  - [Coronary artery bypass with ascending aorta no-touch technics].

PMID- 15854561
TI  - [Adenomatoid tumor of peritoneum--a case report].

PMID- 15854562
TI  - [Molecular imaging of the cardiovascular system].

PMID- 15854563
TI  - [Critical selection of nursing literature].
AB  - The aim of the article is to sensitize nurses to use systematic bibliographic
      review to have a picture of nursing scientific products in nursing domain
      (education, management, research and clinical). It is a must to contribute to the
      scientific development of nursing by methods, tools and critical evaluation
      systems to be able to choose the useful information. To become familiar with
      international literature it is necessary to be familiar with specific
      consultation criteria that respect and are part of a systematic process that can
      be devised in: access, individuation, selection and font utility.

PMID- 15854564
TI  - [Support Strategies and provincial survey on nursing research].
AB  - The Board of Directors of the Nurses College of Venice has started a promotional
      strategy in order to stimulate the nursing research that will be developed in the
      next two years. There will be five different actions. Among them, an annual
      meeting on this subject. During the first of these meetings, a questionnaire has
      been given to the participants, to evaluate their interest for specific topics
      and investigate on their previous research experiences. The results show a
      variety of interests. Nevertheless the main topics are sanitary management and
      work safety. Furthermore, by splitting the preferences by subjects, it has been
      observed a greatest interest for organizational activities, the quality of
      assistance, the clinical nursing and the personal relationship with the
      customers. The collected data show also that only a small amount of participants
      has already managed some research projects that ended up with a scientific
      publication.

PMID- 15854565
TI  - [Professional Master: nurse coordinator University of Milan].
AB  - This article is intended to illustrate the experience of the Medical Faculty of
      the University of Milan, as regards the Master s Program for Nursing Coordinator
      funded by the FSE of the European Union for the Academic year 2003/2004.
      Specifically, this article highlights: Organizational aspects: admission policy,
      theoretical and practical formative planning Methodology used, as applied to
      adult education Course evaluation and observations by the participants.

PMID- 15854566
TI  - [Hearing and information as strategies to better coping abilities in the client].
AB  - The purpose of this issue the importance of the active hearing, participating
      information and the alliance with the client in the helping relation. The
      relation between nurse and client has an essential objective cannot be deferred
      neither delegated because the nursing essence is to restore self government to
      the client. The nurse can better the approach with the un-defended client, to
      face prejudicial factors and to apply strategies to develop the coping.

PMID- 15854567
TI  - [Eficiency, equity or eficacy? Is it nurses or health systems dilemma?].
AB  - Besides the increasing costs of health technologies and the epidemic and
      demographic transactions, the causes of the current inadequacy of resources in
      the health field are also to be ascribed to people changed expectations toward
      nursing and medicine. Such aspects have put in a critical position the working of
      the health services, which are incapable of facing the escalating and relentless
      health expenses. The evidence-based approach to the clinical practice and the
      following output of guidelines as a solution to the rationing of health services,
      may, in someone opinion, make headway towards the control of expenditure because
      it allows a synergy between optimal and basic principles. The reasoned use of the
      resources does not only presuppose that nurses can decide, as far as the patient
      is concerned, what is strictly necessary and at the same time most effective to
      the fulfillment of the nursing needs which have been pinpointed; nurses should
      also commit themselves to organise for the best, according to their level of
      responsibility, the scenario where clinic decisions are taken and to affect the
      guidance processes of the strategic choices of the institution they are part of.
      Nurses, as other professional do, have to honour also a commission which implies,
      on different levels, to take on an executive function, a teamwork function, an
      active and responsible cooperation in the working of health service. A
      superficial and cursory use of the guidelines as an allocation of resources
      might, on the other hand, raise objections in the name of ethics: health cannot
      be treated as a commodity, nor can health be subjected to market laws of supply
      and demand. The degree of legitimation of a health policy must therefore derive
      from the degree of harmonization and coherence between an evidence element and a
      social and cultural context where both have to be put a test.

PMID- 15854568
TI  - Identification of vehicle design requirements for older drivers.
AB  - The proportion of older people in the population is rising, as is the proportion
      of older women driving licence holders. The needs and abilities of older drivers
      therefore need to be considered in vehicle design. Following some initial focus
      groups an extensive nation-wide postal survey was conducted to ascertain the type
      and degree of problems associated with automotive design for older drivers and to
      guide further research into the most appropriate areas. Over a thousand
      questionnaires were received. Findings indicate that particular difficulties are
      experienced significantly more often by older drivers than younger drivers, in
      particular turning to look out of the rear window and getting in and out of the
      car. Reasons for these were ascertained and are reported here. The findings have
      guided a subsequent research project into the factors affecting ease of entry and
      exit by older drivers.

PMID- 15854569
TI  - An integrated analysis of ergonomics and time consumption in Swedish 'craft-type'
      car disassembly.
AB  - Car disassembly is at the edge of extensive rationalization due to increased
      legislative demands for recycling. This study focused on (1) assessing current
      mechanical exposures (physical work loads) for comparison with future
      rationalised systems, with particular emphasis on time aspects, (2) analysing
      disassembly work in terms of time consumption and exposures in constituent tasks
      as defined by a loss analysis technique, and (3) predicting the consequences of
      car disassembly rationalisation for mechanical exposures. The study showed that
      disassembly implied pronounced circulatory loads, and that more walking and
      higher lumbar peak loads were found than in studies of assembly work. Value
      adding tasks comprised 30% of the total working time, and implied higher postural
      exposures for the head, arm, trunk and wrist, as well as less opportunities to
      recover, as compared to non-value-adding tasks. Organisational-type
      rationalization can be expected to increase the time spent in value-adding work,
      thus increasing local exposures for the average worker, while a concurrent
      increase in mechanization level might reduce circulatory exposures, the amount of
      walking, and peak lumbar loads.

PMID- 15854570
TI  - Workload of window cleaners using ladders differing in rung separation.
AB  - The objective of the present study was to compare energetic workload, perceived
      exertion, perceived discomfort, safety, and mechanical load at lower limb joints
      among window cleaners during usage of extension ladders with 30 and 35 cm rung
      separation. Eleven healthy male professional window cleaners of short and tall
      stature participated in this study. No significant differences between 30 and 35
      cm rung separation were observed for the energetic workload. Results concerning
      the perceived exertion, discomfort, and safety indicate that 35 cm rung
      separation is preferred. Based on the mechanical load at the hip, knee, and ankle
      during ascending and descending the ladder, 30 cm rung separation is preferable
      to 35 cm rung separation. It is advised to climb ladders with the knees inside
      the side rails of the ladder, but this seems only possible with 35 cm rung
      separation. Findings of the presents study suggest that overall, a 35 cm rung
      separation is marginally favourable while using extension ladders.

PMID- 15854571
TI  - The development of a quantitative flexibility test for body armour and comparison
      with wearer trials.
AB  - In this paper a mechanical flexibility test is developed which can be used to
      assess multi layer body armour systems. This is compared with a subjective manual
      test, and then with the results of wearer trials conducted using the recently
      approved ISO body armour standard ISO 14876-1 (2002). A series of trials was
      conducted on six different ballistic and/or stab resistant body armour types with
      a variety of protection levels and constructions. These were tested using the
      mechanical test system in which the armour was forced through a 200 mm hole by a
      100 mm hemispherical plunger. The results of this test were then compared to a
      second set of trials in which flexibility of the same armour was assessed by
      manual handling and flexing of the armour. Finally an ergonomic wearer trial was
      conducted with four armours according to ISO 14876-1 (2002) each armour being
      assessed by four volunteers and the results compared to flexibility data
      collected in the first two trials. It was shown that the mechanical flexibility
      test produced results which were in good agreement with a purely subjective
      flexibility assessment. These results in turn showed reasonable but not exact
      correlation with the wearer trials. The ISO wearer trials addressed other factors
      such as overall comfort and fit of the systems and so the results were not purely
      a function of flexibility.

PMID- 15854572
TI  - Effect of a splint on measures of sustained grip exertion under different forearm
      and wrist postures.
AB  - Despite the facts that gripping tasks have been found to be highly correlated
      with CTS and that splints are gaining popularity as personal protective
      equipment, the influence of splints on grip performance has not been determined
      adequately. The present study intends to investigate the influence of splints
      without the volar parts as well as of forearm and wrist postures on grip
      performances including maximal volitional contraction (MVC), maximum acceptable
      sustained time (MAST), cumulated exertion output (CEO), and normalized exertion
      level (NEL). Twenty college-student volunteers, 10 males and 10 females, were
      recruited. The factors of interest were gender, forearm position, wrist
      deviation, and splint (with and without). The forearm positions were set at 30
      degrees internal shoulder rotation, 0 degrees internal shoulder rotation, and 30
      degrees external shoulder rotation, the angles being measured between the
      sagittal plane and the long axis of dominant forearm. The wrist deviations were
      extension 30 degrees , neutral, and flexion 30 degrees , the angles being
      measured between the sagittal plane and the long axis of the grip gauge. The
      results indicate that the gender effect is the most dominantly significant on all
      evaluated response variables. Males have more MVC (220 vs. 337N), longer MAST
      (20.2 vs. 10.5s), and greater CEO (4306 vs. 1638Ns), but less NEL (66.6 vs.
      73.9%MVC). The forearm posture is shown to be significant only on MVC. In
      addition, the effect of wrist posture cannot shift all responses, nor can the
      effect of splints. In general, a splint without volar part seems to be
      recommended while performing infrequent and forceful gripping tasks under the
      consideration of prevention, but there should be more information about the
      application of a splint without volar part while performing a repetitively
      gripping task.

PMID- 15854573
TI  - An investigation of thermal comfort inside an automobile during the heating
      period.
AB  - This paper describes a combined theoretical and experimental study of thermal
      comfort during the heating period inside an automobile. To investigate the
      effects of thermal conditions on the human physiology and thermal comfort during
      the heating period, temperature, humidity and air velocity were measured at a
      number of points inside the automobile, so thermal conditions were accurately
      determined. The human body was divided into 16 sedentary segments, and the change
      of temperature was observed both experimentally and theoretically. During
      transient conditions of the heating period, heat and mass transfer between the
      human body and the interior environment of an automobile were simulated by a
      computational model, and predictions were compared with the measured data. It is
      shown that there is a good agreement between the model predictions and
      experimental results. By means of the present model, the effects of the fast
      transient conditions of the heating period on the sensible and latent heat
      transfer from the body, body segments skin temperatures and thermal sensation
      were investigated in detail.

PMID- 15854574
TI  - Train drivers' sleep and alertness during short relay operations.
AB  - Within Australia, there has been a recent expansion of relay working operations.
      To address concerns about the amount of sleep obtained by drivers in relay vans,
      and potential deficits in alertness associated with relay work, the current study
      assessed the sleep behaviour and alertness of 15 train drivers working short (<48
      h) relay operations. In total, drivers obtained 8-12h of sleep during the relay
      trip (which took approx 40 h). Overall, they reported that they felt more alert
      following each sleep period. Drivers were able to sustain attention during the 10
      min vigilance tasks administered before and after each shift. These findings
      suggest that the amount of sleep obtained in crew vans during short relay
      operations is sufficient to maintain alertness during the trip. They also
      emphasise the importance of scheduling shifts to maximise the number of sleep
      opportunities that occur between 2200 and 0700 h.

PMID- 15854575
TI  - Concordance between VDU-users' ratings of comfort and perceived exertion with
      experts' observations of workplace layout and working postures.
AB  - The aim of the present study was to evaluate the concordance (agreement) between
      VDU-users' ratings of comfort and ergonomists' observations of workplace layout,
      and the concordance between VDU-users' ratings of perceived exertion and
      ergonomists' observations of working postures during VDU-work. The study
      population consisted of 853 symptom free subjects. Data on perceived comfort in
      different dimensions and data regarding perceived exertion in different body
      locations were collected by means of a questionnaire. Data concerning workplace
      layout and working postures were collected with an observation protocol, by an
      ergonomist. Concordance between ratings of comfort and observations of workplace
      layout was reasonably good for the chair and the keyboard (0.60, 0.58) and good
      regarding the screen and the input device (0.72, 0.61). Concordance between
      ratings of perceived exertion and observations of working postures indicated good
      agreement (0.63-0.77) for all measured body locations (neck, shoulder, wrist and
      trunk). In conclusion ratings of comfort and perceived exertion could be used as
      cost-efficient and user-friendly methods for practitioners to identify high
      exposure to poor workplace layout and poor working postures.

PMID- 15854576
TI  - An ergonomic intervention to reduce back strain among apple harvest workers in
      New York State.
AB  - The impact of modifications to the apple picking bucket on common picking
      postures, self-reported comfort, ease of use, and speed of harvest were measured.
      Fourteen apple pickers wore an intervention hip belt, were interviewed and
      measured using posture-activities-tools-handling methodology. The use of hip belt
      did not significantly alter time spent in various postures. 78.6% of interviewed
      workers preferred the modified bag, 71.4% noted a difference in the back, neck,
      or shoulder, while 64.3% said regular use of modified bag would slow their work.
      Major themes in worker comments are discussed. The hip belt modification to apple
      harvest bag seems generally acceptable to workers, but needs further development
      to overcome unintended effects. Although work sampling demonstrates that the bag
      does not affect work practices, workers appear somewhat concerned that
      productivity will be negatively impacted. Further training of workers in the use
      and potential benefits of bag are needed.

PMID- 15854577
TI  - Effects of increasing visual load on aurally and visually guided target
      acquisition in a virtual environment.
AB  - The aim of the present study is to investigate interactions between vision and
      audition during a target acquisition task performed in a virtual environment. We
      measured the time taken to locate a visual target (acquisition time) signalled by
      auditory and/or visual cues in conditions of variable visual load. Visual load
      was increased by introducing a secondary visual task. The auditory cue was
      constructed using virtual three-dimensional (3D) sound techniques. The visual cue
      was constructed in the form of a 3D updating arrow. The results suggested that
      both auditory and visual cues reduced acquisition time as compared to an uncued
      condition. Whereas the visual cue elicited faster acquisition time than the
      auditory cue, the combination of the two cues produced the fastest acquisition
      time. The introduction of secondary visual task differentially affected
      acquisition time depending on cue modality. In conditions of high visual load,
      acquiring a target signalled by the auditory cue led to slower and more error
      prone performance than acquiring a target signalled by either the visual cue
      alone or by both the visual and auditory cues.

PMID- 15854578
TI  - Developing an observational instrument to evaluate personal computer keyboarding
      style.
AB  - While computer use is considered to be a risk factor for musculoskeletal
      disorders of the upper extremity (MSD-UE), there is currently little information
      on how the fingers, hand and thumb are used during keyboarding, and no means to
      document their postures and motions. A computer keyboarding observational
      instrument, termed the Personal Computer Keyboarding Style (PeCKS), is being
      developed to meet this need. The goal of this paper is to describe the process by
      which the PeCKS was developed. Literature on MSD-UE was reviewed and discussions
      were held with content experts to develop criterion-based items considered to be
      potential risk factors for MSD-UE during keyboard use. These items were
      systematically reviewed and rated by seven experts using the Delphi technique.
      These ratings were used to determine which items to retain and which to discard,
      resulting in 19 items to define keyboarding style. The PeCKS, when further
      psychometric testing is completed, will be useful to document and assess
      keyboarding to identify those individuals who may be at risk for MSD-UE.

PMID- 15854579
TI  - Effects of shoe inserts and heel height on foot pressure, impact force, and
      perceived comfort during walking.
AB  - Studying the impact of high-heeled shoes on kinetic changes and perceived
      discomfort provides a basis to advance the design and minimize the adverse
      effects on the human musculoskeletal system. Previous studies demonstrated the
      effects of inserts on kinetics and perceived comfort in flat or running shoes. No
      study attempted to investigate the effectiveness of inserts in high heel shoes.
      The purpose of this study was to determine whether increasing heel height and the
      use of shoe inserts change foot pressure distribution, impact force, and
      perceived comfort during walking. Ten healthy females volunteered for the study.
      The heel heights were 1.0cm (flat), 5.1cm (low), and 7.6cm (high). The heel
      height effects were examined across five shoe-insert conditions of shoe only;
      heel cup, arch support, metatarsal pad, and total contact insert (TCI). The
      results indicated that increasing heel height increases impact force (p<0.01),
      medial forefoot pressure (p<0.01), and perceived discomfort (p<0.01) during
      walking. A heel cup insert for high-heeled shoes effectively reduced the heel
      pressure and impact force (p<0.01), an arch support insert reduced the medial
      forefoot pressure, and both improved footwear comfort (p<0.01). In particular, a
      TCI reduced heel pressure by 25% and medial forefoot pressure by 24%, attenuate
      the impact force by 33.2%, and offered higher perceived comfort when compared to
      the non-insert condition.

PMID- 15854580
TI  - Survey instrument for the universal design of consumer products.
AB  - Universal design is a process intended to include all user groups in product or
      environmental design. The objective of this study was to develop a usability
      testing survey instrument to inform how well consumer products complied with
      established principles of universal design. Thirty-six adults, aging adults and
      adult wheelchair users performed standardized tasks with pens, food storage
      containers, pliers and calculators, and for each task responded to a preliminary
      set of survey items and rated task difficulty. Factor analysis of the survey
      responses produced an eleven-factor solution that accounted for 67% of the
      variance in scores and corresponded fairly closely to the principles of universal
      design. Analysis of scale scores developed from each factor showed that some of
      the scales were sensitive to product feature and user group differences, and were
      negatively associated with perceived task difficulty. Such a tool may aid
      designers who intend their products for user groups of diverse abilities and
      preferences.

PMID- 15854581
TI  - Maximum isoinertial lifting capabilities for different lifting ranges and
      container dimensions.
AB  - The aim of this study was to examine the effects of lifting range and container
      dimension on human maximum isoinertial lifting capability in the sagittal plane.
      Ten young and experienced lifters were tested for their maximum isoinertial
      lifting capabilities for 12 different lifting conditions (three lifting ranges x
      four container dimensions). The results showed that lifting range and container
      dimension significantly affected human maximum isoinertial lifting capability.
      The order for the highest to lowest lifting capability for the three lifting
      ranges was FK (from floor to knuckle height, 0-74 cm), FS (from floor to shoulder
      height, 0-141 cm) and KS (from knuckle height to shoulder height, 74-141 cm)
      regardless of the container dimension, and for the four container dimensions was
      50 x 35 x 15 cm(3), 70 x 35 x 15 cm(3), 50 x 50 x 15 cm(3) and 70 x 50 x 15 cm(3)
      regardless of the lifting range. The mean(SD) maximum isoinertial lifting
      capability ranged from 29.3(3.3) kg for the combination of KS range and 70 x 50 x
      15 cm(3) container to 53.2(5.7)kg for the combination of FK range and 50 x 35 x
      15 cm(3) container. The results of this study can help our knowledge of human
      maximum isoinertial lifting capability and designing the upper limit of lifting
      weight.

PMID- 15854582
TI  - Head and facial anthropometry of mixed-race US Army male soldiers for military
      design and sizing: a pilot study.
AB  - In the United States, the biologically admixed population is increasing. Such
      demographic changes may affect the distribution of anthropometric
      characteristics, which are incorporated into the design of equipment and clothing
      for the US Army and other large organizations. The purpose of this study was to
      examine multivariate craniofacial anthropometric distributions between
      biologically admixed male populations and single racial groups of Black and White
      males. Multivariate statistical results suggested that nose breadth and lip
      length were different between Blacks and Whites. Such differences may be
      considered for adjustments to respirators and chemical-biological protective
      masks. However, based on this pilot study, multivariate anthropometric
      distributions of admixed individuals were within the distributions of single
      racial groups. Based on the sample reported, sizing and designing for the admixed
      groups are not necessary if anthropometric distributions of single racial groups
      comprising admixed groups are known.

PMID- 15854583
TI  - Natriuretic peptide interaction with [3H]isatin binding sites in rat brain.
AB  - Isatin is an endogenous indole, which has a distinct and discontinuous
      distribution in the brain and exhibits a wide range of physiological and
      pharmacological effects. In the present study, we have demonstrated that atrial
      natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) inhibited
      [3H]isatin binding to rat brain sections and isolated membrane fractions. Isatin
      itself antagonised not only natriuretic peptide receptor type A (NPR-A) (ANP
      stimulation of guanylyl cyclase) but also NPR-C (ANP and CNP mediated inhibition
      of adenylyl cyclase) signalling. These results suggest that some [3H]isatin
      binding in the brain may be to NPR-A and NPR-C. Competitive interactions between
      isatin and natriuretic peptides and their receptors give a possible explanation
      of the known anxiogenic effect of low doses of isatin, interacting at NPR-A, and
      the sedative effects of higher doses, antagonising respectively the anxiolytic
      effect of ANP and the anxiogenic effect of CNP.

PMID- 15854584
TI  - Effects of prenatal alcohol exposure on brain-derived neurotrophic factor and its
      receptor tyrosine kinase B in offspring.
AB  - Prenatal alcohol exposure produces many developmental defects in the central
      nervous system. The underlying molecular mechanism, however, has not been fully
      understood. The present study was undertaken to examine the effects of prenatal
      alcohol exposure on brain-derived neurotrophic factor (BDNF) and its receptor
      tyrosine kinase B (TrkB) in offspring. The pregnant Sprague-Dawley rats received
      1 or 3 g/kg of alcohol or an isocaloric solution by intragastric intubation once
      a day from gestational day (GD) 5 to GD 20. On postnatal day 7-8, pups were
      killed and the hippocampus, striatum, cortex, and cerebellum dissected out.
      Levels of BDNF mRNA and proteins, total TrkB proteins and receptor
      phosphorylation were measured. The results showed that prenatal alcohol exposure
      at the dose of 1 g/kg/day did not significantly affect BDNF protein levels in any
      region examined. However, administration of alcohol at the dose of 3 g/kg/day
      markedly reduced levels of BDNF protein and mRNA in the cortex and hippocampus of
      offspring. Western blotting showed that prenatal alcohol exposure at the dose of
      3 g/kg/day also inhibited TrkB phosphorylation in the hippocampus although no
      changes in total TrkB protein levels were observed in any region examined. Our
      data suggest that prenatal alcohol exposure alters both presynaptic and
      postsynaptic BDNF function in certain brain areas of offspring. These alterations
      in BDNF function may contribute to the development of alcohol-related birth
      defects.

PMID- 15854585
TI  - Exaggeration of epileptic-like patterns by nicotine receptor activation during
      the GABA withdrawal syndrome.
AB  - To understand how nicotinic cholinergic receptors may participate in epileptic
      seizures, we tested the effects of nicotine and of the competitive nicotinic
      antagonists dihydro-beta-erythroidine and alpha-bungarotoxin on synaptic
      paroxysmal depolarization shifts (PDSs) and intrinsic bursts of action potentials
      recorded in slices from rats presenting a cortical status epilepticus. This model
      named GABA-withdrawal syndrome (GWS) appears consecutive to the interruption of a
      prolonged intracortical GABA infusion. Effects of both nicotinic antagonists
      suggest a distinct involvement of alpha4-beta2 and alpha7 subunits in shaping
      individual PDSs and patterning repetitive bursts. On one hand, in GWS rats, an
      increase of PDS latency and prolongation of PDS and bursts were induced by
      nicotine and reduced by dihydro-beta-erythroidine, but not by alpha-bungarotoxin.
      The K+ blocker tetraethylammonium also increased duration without changing
      latency. Thus, dihydro-beta-erythroidine-sensitive receptors exert distinct
      controls on the presynaptic generation of PDS and on the process which terminates
      PDSs and bursts. On the other hand, alpha-bungarotoxin depolarized neurons and
      generated rhythmic discharges of clustered bursts. Clustered bursts were also
      observed in slices obtained from GWS rats treated with the acetylcholinesterase
      inhibitor eserine. We suggest that both dihydro-beta-erythroidine and alpha
      bungarotoxin-sensitive sites control paroxysmic activities in GWS and could be
      involved in some human and animal epilepsies presenting mutations of nicotinic
      cholinergic receptors.

PMID- 15854586
TI  - Reduced serotonin synthesis during early embryogeny changes effect of subsequent
      prenatal stress on persistent pain in the formalin test in adult male and female
      rats.
AB  - The considerable evidence supporting a role for serotonin (5-HT) in the embryonic
      formation of CNS, mediation of prenatal stress, and pain processing is reviewed.
      Long-term influences of prenatal 5-HT depletion as well as its combination with
      prenatal stress effects on tonic nociceptive system in 90-day-old Wistar rats
      were studied in the formalin test. Pregnant dams were injected with para
      chlorophenylalanine (pCPA, 400 mg/kg/2 ml, ip), producing 5-HT depletion during
      the early period of fetal serotonergic system development. The adult offspring
      from pCPA-treated dams revealed changes in behavioral indices of persistent pain
      (flexing + shaking and licking) in the formalin test (2.5%, 50 microl) that were
      accompanied by irreversible morphological alterations in the dorsal raphe nuclei.
      In the other series of experiments, the role of 5-HT in the mediation of prenatal
      stress on the behavioral indices of persistent pain was investigated in the adult
      offspring from dams with 5-HT depletion followed by restraint stress. Stress
      during the last embryonic week caused much more increase in flexing + shaking and
      licking in the second tonic phase of the response to formalin in offspring from
      pCPA- than saline-treated (control) dams. The former was characterized by
      alterations in the durations of the interphase, the second phase, and the whole
      behavioral response too. In offspring from pCPA-treated dams, sex dimorphism was
      revealed in tonic pain evaluated by licking. Together with our previous results
      in juvenile rats demonstrating the necessity of definite level of prenatal 5-HT
      for normal development of tonic nociceptive system, the present pioneering
      findings obtained in adult rats indicate that prenatal 5-HT depletion causes long
      term morphological abnormalities in the dorsal raphe nuclei accompanied by
      alterations in behavioral indices of tonic pain. Early prenatal 5-HT depletion
      increases vulnerability of tonic nociceptive circuits to the following prenatal
      stress.

PMID- 15854587
TI  - Sleep disturbances in the rotenone animal model of Parkinson disease.
AB  - Parkinson disease (PD) is characterized by the degeneration of dopaminergic
      neurons in the substantia nigra pars compacta (SNc) and the presence of
      intracytoplasmatic inclusions known as Lewy bodies. Chronic administration of
      rotenone (RT) produces Parkinson's-like symptoms in rats. Because PD patients
      have disrupted sleep patterns, we determined if chronic RT administration
      produces similar changes in rat sleep. RT was administered for 28 days to rats.
      Basal and vehicle (VH) rats received saline or dimethyl sulfoxide and
      polyethylene glycol (1:1), respectively. VH infusion induced a progressive
      decrease in non-rapid eye movement sleep (NREMS) during the 4-week period of VH
      infusion and REMS was reduced in the third and fourth week of VH infusion. VH
      infusion did not induce dopaminergic cell degeneration. Rats receiving RT
      infusion also showed decreased NREMS during the treatment. REMS was dramatically
      reduced on day 7 although subsequently on days 13 and 20 REMS was similar to
      basal values. After 4 weeks of RT infusion, time in REMS was decreased again. In
      RT-treated rats, progressive dopaminergic cell degeneration occurred in the SNc.
      After 4 weeks of daily injections of L-dopa in RT-infused rats, NREMS values
      remained similar to those values obtained after RT alone. L-dopa therapy did,
      however, induce a recovery of REMS in weeks 3 and 4 of RT infusion. Dopaminergic
      cell damage persisted in the L-dopa-RT-infused rats. We conclude that the RT-PD
      rat model is associated with large long-term sleep disruption, however, the
      vehicle, DMSO/PEG had as large an effect as RT on sleep, thus changes in sleep
      cannot be ascribed to loss of dopaminergic cells. Such results question the
      validity of the RT-PD rat model.

PMID- 15854588
TI  - Reactive oxygen species mediate the neuroprotection conferred by a mitochondrial
      ATP-sensitive potassium channel opener during ischemia in the rat hippocampal
      slice.
AB  - Reactive oxygen species (ROS) are known to mediate the protection conferred by
      the opening of mitochondrial ATP-sensitive potassium channels (mitoK(ATP)) during
      ischemia in heart, but this has not been demonstrated in brain. The present study
      examined whether ROS mediate the neuroprotection conferred by a mitoK(ATP) opener
      during ischemia in rat hippocampal slices. Ischemia was simulated by oxygen and
      glucose deprivation. The direct current potential and population spike were
      recorded in the stratum pyramidale of the CA1 region, and lactate dehydrogenase
      (LDH) efflux into the medium was assayed. ROS generation was measured
      spectrophotofluorometrically. Pretreatment of slices with diazoxide (DIA, 300
      microM), a mitoK(ATP) opener, (i) prolonged the latency to ischemic
      depolarization and decreased its amplitude, (ii) delayed the onset of population
      spike disappearance and enhanced its recovery after reperfusion, (iii) decreased
      LDH efflux and (iv) increased ROS levels. The effects induced by DIA were
      attenuated by 5-hydroxydecanoic acid (200 microM), a mitoK(ATP) blocker.
      Pretreatment with N-2-mercaptopropionyl glycine (MPG, 500 microM), a ROS
      scavenger, also abrogated the effects induced by DIA, while treatment with MPG
      alone had no effect during normoxia and ischemia. These results indicate that ROS
      participate in the neuroprotection conferred by a mitoK(ATP) opener during
      ischemia.

PMID- 15854589
TI  - Differential environmental exposure alters NMDA but not AMPA receptor subunit
      expression in nucleus accumbens core and shell.
AB  - Environmentally enriched (EE) rats show neurobehavioral differences relative to
      less stimulated, socially isolated (SI) littermates. Although experience
      dependent cortical changes are presumed to underlie learning differences in these
      differentially housed animals, EE rats show reduced reward-seeking behavior and
      altered cytoarchitecture and dopaminergic function in the nucleus accumbens
      (NAcc), a brain area involved in adaptive, goal-directed activity. Given that
      glutamate and its interaction with dopamine regulate motivational and associative
      processing in this brain region, we assessed expression of the NR1 subunit of the
      N-methyl-D-aspartate (NMDA) receptor and the GluR1 subunit of the alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor in the NAcc core and
      shell of EE and SI rats. Our results indicate fewer intensely stained NR1
      immunopositive neurons in both core and shell of EE relative to SI rats. No such
      differences were observed in GluR1 staining. These results suggest that
      environmental experience alters NMDA but not AMPA receptor expression in NAcc.
      Increased expression of the NR1 subunit in the NAcc of SI rats may augment
      impulsivity and reward-seeking behavior relative to EE rats.

PMID- 15854590
TI  - Effects of atorvastatin on blood-brain barrier permeability during L-NAME
      hypertension followed by angiotensin-II in rats.
AB  - Recent studies suggest that 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors, statins, can have direct effects on blood vessels beyond
      their cholesterol-lowering effects. We investigated the effects of atorvastatin
      on the functional and structural properties of blood-brain barrier (BBB) and the
      activity of astrocytes during the N(omega)-nitro-L-arginine methyl ester (L-NAME)
      hypertension followed by angiotensin (ANG) II. We found that decreases in
      concentration of serum catalase and plasma nitric oxide (NO) induced by L-NAME
      were significantly ameliorated by atorvastatin, whereas L-NAME-induced serum
      malondialdehyde and cholesterol concentration increases were significantly
      reduced by atorvastatin. The content of Evans blue (EB) dye significantly
      increased in cerebellum, left cerebral cortex and diencephalon regions but
      atorvastatin markedly reduced the increased BBB permeability to EB in the brain
      regions of animals treated with L-NAME and L-NAME plus ANG II. Brain vessels of L
      NAME-treated animals showed a considerable loss of immunoreactivity of tight
      junction proteins, zonula occludens (ZO)-1 and occludin. Immunoreactivity for ZO
      1 and occludin increased in animals treated with atorvastatin and L-NAME plus
      atorvastatin. Glial fibrillary acidic protein (GFAP) immunoreactivity was seen in
      few astrocytes in the brain sections of L-NAME, but immunoreactivity for GFAP
      increased in L-NAME plus atorvastatin-treated animals. We suggest that long-term
      L-NAME treatment may affect BBB permeability through disruption of tight junction
      proteins, at least partly, via decreased NO concentration and increased oxidant
      capacity; the improvement of BBB integrity and astrocytic activity would be more
      closely associated with the action of atorvastatin favoring the increase in anti
      oxidant capacity and expression of tight junction proteins and GFAP.

PMID- 15854591
TI  - Gradual enlargement of human withdrawal reflex receptive fields following
      repetitive painful stimulation.
AB  - Dynamic changes in the topography of the human withdrawal reflex receptive fields
      (RRF) were assessed by repetitive painful stimuli in 15 healthy subjects. A train
      of five electrical stimuli was delivered at a frequency of 3 Hz (total train
      duration 1.33 s). The train was delivered in random order to 10 electrode sites
      on the sole of the foot. Reflexes were recorded from tibialis anterior, soleus,
      vastus lateralis, biceps femoris, and iliopsoas (IL). The RRF changes during the
      stimulus train were assessed during standing with even support on both legs and
      while seated. The degree of temporal summation was depending on stimulation site.
      At the most sensitive part of the RRF, a statistically significant increase in
      reflex size was seen after two stimuli while four stimuli were needed to observe
      reflex facilitation at less sensitive electrode sites. Hence, the region from
      which reflexes could be evoked using the same stimulus intensity became larger
      through the train, that is, the RRF was gradually expanding. Reflexes evoked by
      stimuli four and five were of the same size. No reflex facilitation was seen at
      other stimulus sites outside the RRF. In all muscles except in IL, the largest
      reflexes were evoked when the subjects were standing. In the ankle joint, the
      main withdrawal pattern consisted of plantar flexion and inversion when the
      subjects were standing while dorsi-flexion was prevalent in the sitting position.
      Up to 35 degrees of knee and hip flexion were evoked often leading to a lift of
      the foot from the floor during standing. In conclusion, a gradual expansion of
      the RRF was seen in all muscles during the stimulus train. Furthermore, the motor
      programme task controls the reflex sensitivity within the reflex receptive field
      and, hence, the sensitivity of the temporal summation mechanism.

PMID- 15854592
TI  - The cardiac-related rhythm in preganglionic sympathetic activities of developing
      piglets.
AB  - This investigation was performed to determine whether partial spectral analysis
      of preganglionic sympathetic nerve discharges would reveal age-related
      differences in the distribution of baroreceptor afferent information to brainstem
      sympathetic-related neurons. Any influence of baroreceptor afferent activity on
      ordinary spectra of cervical sympathetic and splanchnic nerves was removed by
      partialization using the arterial blood pressure signal which represented
      baroreceptor activity. An absence of statistically significant coherence in
      partialized nerve spectra would indicate that sympathetic-related neurons receive
      peripheral baroreceptor afferent input, but are not interconnected, whereas the
      presence of significant coherence would mean that these neurons are
      interconnected. Ordinary spectral analysis did not demonstrate age-related
      differences in the relationship between nerve activity and baroreceptor afferent
      input. In many animals, large peaks, located at cardiac frequencies (range 2.75
      5.6 Hz), were noted in ordinary nerve autopower spectra, and were significantly
      correlated in ordinary coherence spectra. Partialization of nerve spectra
      eliminated or reduced cardiac-related peaks in autopower spectra regardless of
      age, and, in 8 of 10 animals, reduced coherence estimates to non-significant
      values. In two animals, 19 and 36 days old, significant coherence values remained
      after partialization. These results demonstrated that cardiac-related peaks in
      coherence in spectra of preganglionic splanchnic and cervical sympathetic nerves
      were dependent upon peripheral afferent baroreceptor input in most animals.
      Further, the finding that significant residual coherence was absent in most cases
      suggested a paucity of intrabulbar pathways connecting brainstem sympathetic
      related neurons.

PMID- 15854593
TI  - Transient forebrain ischemia effects interaction of Src, FAK, and PYK2 with the
      NR2B subunit of N-methyl-D-aspartate receptor in gerbil hippocampus.
AB  - Two different models of brain ischemia were used to examine the evoked changes in
      the tyrosine phosphorylation of NMDA receptor subunits 2A and 2B (NR2A and NR2B),
      as well as their interactions with non-receptor tyrosine kinases (NRTKs: FAK,
      PYK2 Src), and PSD-95 protein. Only short-term 5 min ischemia followed by 3 h
      reperfusion resulted in the elevated tyrosine phosphorylation of both
      investigated NMDA receptor subunits, but in contrast to previously published
      data, more pronounced in the case of NR2B. Concomitantly, an increased
      association of NR2B with FAK, PYK2, Src and PSD-95 has been observed. This sharp
      early reaction to brief ischemia was markedly attenuated during prolonged
      recovery (72 h) with almost complete return to control values. The initial
      recruitment of tyrosine kinases to NMDA receptor during the first 3 h of
      reperfusion is generally consistent with an active postischemic remodeling of PSD
      and may participate in the induction of the postischemic signal transduction
      pathway in gerbil hippocampus. In contrast, ischemia of longer duration (up to 30
      min) caused an immediate decrease in the protein levels as well as tyrosine
      phosphorylation of both NR2A and NR2B subunits which was accompanied by the
      marked attenuation of the association with their investigated molecular partners-
      PSD-95 and NRTKs. This effect may be mimicked in vitro by Ca2+-dependent
      activation of endogenous calpains in purified PSD preparation suggesting
      irreversible deterioration of the synaptic signaling machinery during
      irreversible long-term ischemia.

PMID- 15854594
TI  - Quantitative analysis of immunolabeling for serotonin and for glutamate
      transporters after administration of imipramine and citalopram.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) is an amine neurotransmitter derived from
      tryptophan and is important in brain systems regulating mood, emotional behavior,
      and sleep. Selective serotonin reuptake inhibitor (SSRI) drugs are used to treat
      disorders such as depression, stress, eating disorders, autism, and
      schizophrenia. It is thought that these drugs act to prolong the action of 5-HT
      by blocking reuptake. This may lead to decreased 5-HT content in the nerve fibers
      themselves; however, this has not previously been directly demonstrated. We have
      studied the effects of administration of two drugs, imipramine and citalopram, on
      levels of 5-HT in nerve fibers in the murine brain. Quantitative analysis of the
      areal density of 5-HT fibers throughout the brain was performed using ImageJ
      software. While a high density of fibers was observed in mid- and hind-brain
      regions and areas such as thalamus and hypothalamus, densities were far lower in
      areas such as cortex, where SSRIs might be thought to exert their actions. As
      anticipated, imipramine and citalopram produced a decline in 5-HT levels in nerve
      fibers, but the result was not uniform. Areas such as inferior colliculus showed
      significant reduction whereas little, if any, change was observed in the adjacent
      superior colliculus. The reason for, and significance of, this regionality is
      unclear. It has been proposed that serotonin effects in the brain might be linked
      to changes in glutamatergic transmission. Extracellular glutamate levels are
      regulated primarily by glial glutamate transporters. Qualitative evaluation of
      glutamate transporter immunolabeling in cortex of control and drug-treated mice
      revealed no discernable difference in intensity of glutamate transporter
      immunoreactivity. These data suggest that changes in intracellular and
      extracellular levels of serotonin do not cause concomitant changes in astroglial
      glutamate transporter expression, and thus cannot represent a mechanism for the
      delayed efficacy of antidepressants when administered clinically.

PMID- 15854595
TI  - Effects of age, gender, and weight on the cerebellar volume of Korean people.
AB  - The average cerebellar volume of Korean men (135.19 cm3) is larger than that of
      Korean women (123.06 cm3), and that of subjects in their twenties (134.28 cm3) is
      larger than that of subjects in their forties (121.83 cm3). Atrophy of the
      cerebellum is more markedly observed in men than in women. There is a relation
      between body weight and cerebellar volume for men, but not for women.

PMID- 15854596
TI  - Induction of DNA repair proteins, Ref-1 and XRCC1, in adult rat brain following
      kainic acid-induced seizures.
AB  - We evaluated the expression of DNA repair proteins, redox factor-1 (Ref-1) and X
      ray repair cross-complementing protein 1 (XRCC1), relevant to neurodegeneration
      following kainic acid-induced seizures in rats. Neurons with oxidative DNA damage
      exhibited increased expression and colocalization of Ref-1 and XRCC1.
      Upregulation of DNA repair proteins was also associated with p53 induction and
      TUNEL. Coexpression of DNA repair proteins and cell death markers following
      seizures suggests that the DNA repair response may not be sufficient to prevent
      excitotoxin-induced neurodegeneration.

PMID- 15854597
TI  - Syntheses of T(N) building blocks Nalpha-(9-fluorenylmethoxycarbonyl)-O-(3,4,6
      tri-O-acetyl-2-azido-2-deoxy-alpha-D-galactopyranosyl)-L-serine/L-threonine
      pentafluorophenyl esters: comparison of protocols and elucidation of side
      reactions.
AB  - T(N) antigen building blocks Nalpha-(9-fluorenylmethoxycarbonyl)-O-(3,4,6-tri-O
      acetyl-2-azido-2-deoxy-alpha-D-galactopyranosyl)-L-serine/L-threonine
      pentafluorophenyl ester [Fmoc-L-Ser/L-Thr(Ac3-alpha-D-GalN3)-OPfp, 13/14] have
      been synthesized by two different routes, which have been compared. Overall
      isolated yields [three or four chemical steps, and minimal intermediary
      purification steps] of enantiopure 13 and 14 were 5-18% and 6-10%, respectively,
      based on 3,4,6-tri-O-acetyl-D-galactal (1). A byproduct of the initial
      azidonitration reaction of the synthetic sequence, that is, N-acetyl-3,4,6-tri-O
      acetyl-2-azido-2-deoxy-alpha-D-galactopyranosylamine (5), has been characterized
      by X-ray crystallography, and shown by 1H NMR spectroscopy to form complexes with
      lithium bromide, lithium iodide, or sodium iodide in acetonitrile-d3.
      Intermediates 3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-galactopyranosyl bromide
      (6) and 3,4,6-tri-O-acetyl-2-azido-2-deoxy-beta-D-galactopyranosyl chloride (7)
      were used to glycosylate Nalpha-(9-fluorenylmethoxycarbonyl)-L-serine/L-threonine
      pentafluorophenyl esters [Fmoc-L-Ser/L-Thr-OPfp, 11/12]. Previously undescribed
      low-level dehydration side reactions were observed at this stage; the unwanted
      byproducts were easily removed by column chromatography.

PMID- 15854598
TI  - Diastereoselective annulation of 4-hydroxypyran-2H-ones with enantiopure 2,3
      dideoxy-alpha,beta-unsaturated sugar aldehydes derived from respective glycals.
AB  - One-pot condensations of 4-hydroxypyran-2H-ones 1 and 2, respectively, with
      various enantiopure 2,3-dideoxy-alpha,beta-unsaturated carbohydrate enals in the
      presence of l-proline in EtOAc at room temperature generated pyrano-pyrones. It
      was observed that, while benzyl-protected carbohydrate enals on condensation with
      1 or 2 under the above conditions produced an inseparable diastereomeric mixture
      in a ratio of 1:1, the acyl-protected carbohydrate enals on treatment with 1 or 2
      under identical conditions yielded products with moderate to very high
      diastereoselectivity. A remarkable asymmetric induction was noticed from the C-4
      stereogenic center of the acyl-protected carbohydrate enals. An almost complete
      diastereoselectivity was observed in those reactions that involved condensation
      of 1 with acetyl-protected enals 5 and 7. The reaction of 2 with 5 also proceeded
      diastereoselectively to furnish the corresponding annulated product. The reaction
      presumably took place by C-1,2-addition of the pyrone onto the iminium salt of
      the alpha,beta-unsaturated carbohydrate enal generated in situ, followed by beta
      elimination and cyclization of the 1-oxatriene involving a 6pi-electron
      electrocyclic process to yield a 2H,5H-pyrano[3,2-c]pyran-5-one derivative.

PMID- 15854599
TI  - Highly functionalised cyclobutanols via samarium(II) iodide-induced pinacol
      cyclisations of carbohydrate-derived 1,4-diketones.
AB  - D-Ribofuranose and D-arabinofuranose derivatives were converted in a few steps
      into their 1,4-diketone derivatives, which were pinacol cyclised under the action
      of SmI2 to form the corresponding chiral cyclobutanediol products. These products
      can potentially be applied to the synthesis of anti-viral agents, some of whose
      structures incorporate chiral cyclobutanediol moieties.

PMID- 15854600
TI  - Enzymatic synthesis of a new inhibitor of alpha-amylases: acarviosinyl
      isomaltosyl-spiro-thiohydantoin.
AB  - Synthesis of acarviosinyl-isomaltosyl-spiro-thiohydantoin in yields up to 20%,
      has been achieved by Bacillus stearothermophilus maltogenic amylase (BSMA). BSMA
      is capable of transferring the acarviosine-glucose residue from an acarbose donor
      onto glucopyranosylidene-spiro-thiohydantoin. Reactions were followed using HPLC
      and MALDI-TOF MS. 1H and 13C NMR studies revealed that the enzyme reserved its
      stereoselectivity. Glycosylation took place mainly at C-6 resulting in alpha
      acarviosinyl-(1-->4)-alpha-D-glucopyranosyl-(1-->6)-D-glucopyranosylidene-spiro
      thiohydantoin. This compound was found to be a much more efficient salivary
      amylase inhibitor than glucopyranosylidene-spiro-thiohydantoin with kinetic
      constants of K(EI)=0.19 microM and K(ESI)=0.24 microM.

PMID- 15854601
TI  - Endoxylanase substrate selectivity determines degradation of wheat water
      extractable and water-unextractable arabinoxylan.
AB  - The relative activity of an endoxylanase towards water-unextractable (WU-AX) and
      water-extractable arabinoxylan (WE-AX) substrates, referred to as endoxylanase
      substrate selectivity, impacts the enzyme functionality in cereal-based
      biotechnological processes such as bread-making and gluten starch separation. A
      set of six endoxylanases representing a range of substrate selectivities as
      determined by a screening method using chromophoric substrates [Anal.
      Biochem.2003, 319, 73-77] was used to examine the impact of such selectivity on
      changes in structural characteristics of wheat WU-AX and WE-AX upon enzymic
      hydrolysis. While WE-AX degradation by the selected endoxylanases was very
      comparable with respect to apparent molecular mass (MM) profiles and arabinose to
      xylose ratio of the hydrolysates formed, WU-AX solubilisation and subsequent
      degradation of solubilised fragments gave rise to widely varying MM profiles,
      depending on the substrate selectivity of the enzymes. Enzymes with high
      selectivity towards WU-AX de facto generated higher MM fragments from WU-AX than
      enzymes with low selectivity. The arabinose to xylose ratios of solubilised
      fragments were independent of the degree of solubilisation.

PMID- 15854602
TI  - Diastereoisomeric saponins from Albizia julibrissin.
AB  - The structures of four new diastereoisomeric triterpenoidal saponins Julibroside
      J5, J8, J12 and J13 (1-4) isolated from Albizia julibrissin Durazz. (Leguminosae)
      have been determined on the basis of comprehensive spectroscopic analysis and
      chemical degradation. Julibroside, J8 and J13 showed marked cytotoxic activities
      against Bel-7402 cancer cell line at 100 microg/mL.

PMID- 15854603
TI  - Mango ripening--chemical and structural characterization of pectic and
      hemicellulosic polysaccharides.
AB  - Ripening of mango is characterized by a gradual, but natural softening of the
      fruit, which is due to progressive depolymerization of pectic and hemicellulosic
      polysaccharides with significant loss of galactose, arabinose and mannose
      residues at the ripe stage. Structural characterization employing permethylation
      followed by GC-MS analysis, IR and 13C NMR measurements revealed the major CWS
      fractions of both unripe and ripe mangoes to be of variable molecular weights and
      having a 1,4-linked galactan/galacturonan backbone, which is occasionally
      involved in side chain branches consisting of single residues of galactose and
      arabinose or oligomeric 1,5-linked arabinofuranose residues linked through 1,3
      linkages; whereas the major hemicellulosic fractions of unripe mango to be of
      xyloglucan-type having 1,4-linked glucan backbone with branching by non-reducing
      terminal arabinose and xylose residues.

PMID- 15854604
TI  - Application of ultra-high magnetic field for saccharide molecules: 1H NMR spectra
      of 6-O-alpha-D-glucopyranosyl-cyclomaltoheptaose and -cyclomaltohexaose.
AB  - 1H NMR spectra of G1-alpha-CD and G1-beta-CD were recorded using a spectrometer
      equipped with a 21.6 T magnet. An ultra-high magnetic field was effective for
      detecting 1H NMR signals with a small difference in chemical shifts. Introducing
      a glucosyl group onto CDs as a branch caused deformation of equilibrated 1H
      signals of cyclodextrin. Particularly, 1H signals in branched glucose were
      shifted greatly.

PMID- 15854605
TI  - Preparation of carboxymethyl chitosan in aqueous solution under microwave
      irradiation.
AB  - Carboxymethyl chitosan was prepared by reacting chitosan with chloroacetic acid
      in water under microwave irradiation. The effect of the reaction conditions was
      investigated and optimal conditions were identified. The influence of mass ratio
      of chloroacetic acid to chitosan, microwave power and pH on the degree of
      substitution or intrinsic viscosity were further studied. The degree of
      substitution of the carboxymethyl chitosan synthesized exceeded 0.85.

PMID- 15854606
TI  - Seaweed processing using industrial single-mode cavity microwave heating: a
      preliminary investigation.
AB  - A single-cavity microwave heating system has been designed and fabricated for
      microwave-assisted extraction of carrageenans from seaweed. The system comprises
      a single mode (TE101) waveguide fitted with power and temperature controls,
      together with a continuous-flow-recycle reactor operating at atmospheric
      pressure. The system has been tested by extraction of E. cottonii and E. spinosum
      in aqueous organic solvents. Even without purification, the extraction products
      were found to have virtually identical FTIR and 13C and 1H NMR spectra to the
      reference samples of kappa- and iota-carrageenan, respectively. The principal
      advantages of the microwave system are substantial reduction of extraction time
      and low consumption of organic solvents.

PMID- 15854607
TI  - Oxidation of gum arabic by soluble colloidal MnO2.
AB  - In the present work, the oxidative degradation of gum arabic by colloidal
      manganese dioxide (MnO2) was carried out. Monitoring the disappearance of the
      MnO2 spectrophotometrically at 375 nm was used to follow the kinetics. The
      oxidation obeyed fractional-order kinetics with respect to the [gum arabic].
      Effect of various experimental parameters such as the initial colloidal [MnO2],
      [HClO4], temperature, and complexing agents (P2O7(4-), F-, and Mn2+) for the
      oxidation of gum arabic was studied. The reaction was acid catalyzed. Addition of
      P2O(7)4-, F-, and Mn2+ ions enhances the rate of oxidation significantly. Gum
      arabic adsorbs onto the surface of the colloidal MnO2 through the equatorial -OH
      groups of the rhamnose moiety, and the complex breaks down into products. The
      Arrhenius equation was valid for the oxidation kinetics between 40 and 60 degrees
      C. To explain the observed kinetic results, a suitable mechanism and rate law for
      the reaction taking place at the surface of the colloidal particle has been
      proposed. The reducing nature of gum arabic is found be due to the presence of 
      OH group in the skeleton.

PMID- 15854608
TI  - Direct one-pot conversion of acylated carbohydrates into their alkylated
      derivatives under heterogeneous reaction conditions using solid NaOH and a phase
      transfer catalyst.
AB  - A convenient one-pot protocol for the direct conversion of acyl-protected
      carbohydrates into their alkylated counterparts has been developed by using alkyl
      halides in the presence of solid sodium hydroxide and a phase transfer catalyst.
      These economically convenient, mild, two-phase reaction conditions allow the
      preparation of a variety of monosaccharide intermediates for use in the synthesis
      of complex oligosaccharides.

PMID- 15854609
TI  - Synthesis of 2-deoxy-2-(4-nitroimidazol-1-yl)-D-alditols.
AB  - Small molecules possessing defined configuration at centres of chirality provide
      a valuable chiral pool. Among different strategies applied for modification of
      chiral compounds, the most common is to begin with a single stereoisomer and use
      a synthesis that does not affect the chiral centres. The ANRORC type reaction has
      been applied for conversion of unprotected 2-amino-2-deoxy-D-hexopyranoses into 2
      deoxy-2-(4-nitroimidazol-1-yl)-D-hexopyranoses in a reaction of some 2
      aminosugars with 1,4-dinitroimidazoles. The reaction occurs with retention of
      configuration at C-2 of sugar ring. The products of the reaction were obtained as
      anomeric mixtures and separated into anomers after acetylation followed by column
      chromatography. 2-Deoxy-2-(4-nitroimidazol-1-yl)-D-hexopyranoses treated with
      sodium borohydride in methanolic solution gave the corresponding 2-deoxy-2-(4
      nitroimidazol-1-yl)-D-hexitols, characterised as per-O-acetylated derivatives.

PMID- 15854610
TI  - InCl3 as a powerful catalyst for the acetylation of carbohydrate alcohols under
      microwave irradiation.
AB  - Indium(III) chloride catalyzed microwave assisted acetylation of different
      carbohydrates is an efficient synthesis of per-O-acetyl derivatives and provides
      the products in good to excellent yields.

PMID- 15854611
TI  - One-pot synthesis of per-O-acetylated thioglycosides from unprotected reducing
      sugars.
AB  - A sequential per-O-acetylation and thioglycosidation of unprotected reducing
      sugars using a stoichiometric quantity of acetic anhydride and alkyl- or
      arylthiols is reported. These reactions, which are catalyzed by BF3.OEt2,
      together constitute an efficient one-pot method for the synthesis of acetylated
      thioglycosides.

PMID- 15854612
TI  - beta-D-Galactopyranosyl-thiohydroximates and D-galactopyranosylidene-spiro
      oxathiazoles: synthesis and enzymatic evaluation against E. colid-galactosidase.
AB  - By reaction with arylhydroximoyl chlorides, 2,3,4,6-tetra-O-acetyl-1-thio-beta-D
      galactopyranose was converted to the corresponding beta-D-galactopyranosyl
      thiohydroximates, which gave predominantly (1S)-D-galactopyranosylidene-spiro
      oxathiazoles on illumination in the presence of NBS. Conventional O-deacetylation
      of both thiohydroximates and oxathiazoles gave weak inhibitors of E. colid
      galactosidase (Ki 1.1-11.1 mM).

PMID- 15854613
TI  - Facile synthesis of 6-amino-6-deoxycellulose.
AB  - 6-Amino-6-deoxycellulose (4) was synthesized from cellulose by three reaction
      steps, namely bromination at C-6, displacement of bromine by azide ion, and
      reduction of the azide group to amino group, in 67% overall yield. The 13C NMR
      spectrum of compound 4 supports the expected structure for 6-amino-6
      deoxycellulose. The degree of substitution of compound 4 was 0.96.

PMID- 15854615
TI  - Cyclomaltooligosaccharide (cyclodextrin)-assisted enantiomeric recognition of
      benzo[lmn][3,8]phenanthroline-derived amino acids.
AB  - Formation of self-assembly molecular aggregates and cyclomaltooligosaccharide
      (cyclodextrin) molecular aggregates with benzo[lmn][3,8]phenanthroline-derived
      amino acids is presented. The nature of the molecular aggregates was studied by
      negative-ion electrospray-ionization mass spectrometry (ESIMS). The enantiomeric
      recognition was demonstrated by NMR enantiomeric discrimination of the amino acid
      derivatives in aqueous solutions of cyclodextrins.

PMID- 15854614
TI  - Structure of the O-polysaccharide from the lipopolysaccharide of Providencia
      stuartii O43 containing an amide of D-galacturonic acid with L-serine.
AB  - The O-polysaccharide was obtained by mild acid degradation of the
      lipopolysaccharide of Providencia stuartii O43:H28 and studied by sugar and
      methylation analyses, Smith degradation and 1H and 13C NMR spectroscopy,
      including 2D ROESY, and H-detected 1H, 13C HSQC and HMBC experiments, as well as
      a NOESY experiment in a 9:1 H2O/D2O mixture to reveal correlations for NH
      protons. It was found that the polysaccharide is built up of linear
      tetrasaccharide repeating units containing an amide of D-galacturonic acid with L
      serine [D-GalA6(L-Ser)] and has the following structure:[3)-beta-D-GalpA6(L-Ser)
      (1-->3)-beta-D-GlcpNAc-(1-->2)-alpha-D-Rhap4NAc-(1-->4)-beta-D-GlcpA-(1-->]n.

PMID- 15854616
TI  - The O-polysaccharide from the lipopolysaccharide of Providencia stuartii O44
      contains L-quinovose, a 6-deoxy sugar rarely occurring in bacterial
      polysaccharides.
AB  - The O-polysaccharide (O-antigen) of Providencia stuartii O44:H4 (strain 3768/51)
      was obtained by mild acid degradation of the lipopolysaccharide and studied by
      sugar and methylation analyses along with (1)H and (13)C NMR spectroscopy,
      including 2D (1)H,(1)H COSY, TOCSY, ROESY, and H-detected (1)H,(13)C HSQC, and
      HMQC-TOCSY experiments. The O-polysaccharide was found to have a branched
      hexasaccharide repeating unit of the following structure: [Formula: see text].

PMID- 15854617
TI  - Periodate oxidation of sodium alginate in water and in ethanol-water mixture: a
      comparative study.
AB  - Periodate oxidation of sodium alginate in aqueous solution as well as a
      dispersion in 1:1 ethanol-water was examined. The oxidation proceeded smoothly in
      both media, and the kinetics of oxidation was surprisingly similar. Polymer
      cleavage was observed in both media, but it was extensive in ethanol-water. The
      weight-average molar mass (Mw) of the oxidized product obtained from aqueous
      solution showed a gradual decrease with increase in the periodate concentration,
      whereas, except for very high periodate equivalent, the change in Mw was not
      reflected with increase in concentration of periodate in ethanol-water. The
      oxidized alginate obtained from the ethanol-water mixture was found to be more
      efficient in crosslinking proteins such as gelatin, leading to hydrogels.
      Oxidation of a dispersion has the advantage of generating large quantities of the
      oxidized alginate in higher yield with one reaction using less solvent.

PMID- 15854618
TI  - Isolation and characterization of xylans from seed pericarp of Argania spinosa
      fruit.
AB  - Hemicellulose-type polysaccharides were isolated from the pericarp of seeds of
      Argania spinosa (L.) Skeels fruit by sequential alkaline extractions and
      fractionated by precipitation. Water soluble and water insoluble fractions were
      obtained, purified and characterized by sugar analysis and 1H and 13C NMR
      spectroscopy. The water soluble fractions were assumed to be (4-O-methyl-D
      glucurono)-D-xylans, with 4-O-methyl-D-glucopyranosyluronic acid groups linked to
      C-2 of a (1-->4)-beta-D-xylan. The 1H NMR spectrum showed that the water soluble
      xylans have, on average, one non-reducing terminal residue of 4-O-methyl-D
      glucuronic acid for every seven xylose units. The water insoluble fractions
      consisted of a neutral xylan with linear (1-->4)-beta-D-xylopyranosyl units.

PMID- 15854619
TI  - The crystal structure of a cyclic glycolipid reveals a carbohydrate-carbohydrate
      interaction interface.
AB  - The crystal structure of an amphiphilic macrocycle [Velasco-Torrijos, T.; Murphy,
      P. V., Tetrahedron: Asymmetry2005, 16, 261-272] derived from saccharides shows
      extensive hydrogen-bonding networks, including participation of water, that may
      have relevance for the modelling of carbohydrate-carbohydrate recognition at cell
      cell interfaces. The structure may provide a basis for understanding the binding
      of the macrocycle to hydrophobic probes.

PMID- 15854620
TI  - Molecular structure of lathyritol, a galactosylbornesitol from Lathyrus odoratus
      seeds, by NMR.
AB  - The molecular structure of galactosyl-D-(-)-bornesitol, a novel compound isolated
      from sweet pea seeds, was determined to be alpha-D-galactopyranosyl-(1-->3)-1-O
      methyl-1D-myo-inositol by 1D and 2D NMR spectroscopy and is assigned the trivial
      name lathyritol.

PMID- 15854621
TI  - Synthesis and mesomorphic properties of glycosyl dialkyl- and diacyl-glycerols
      bearing saturated, unsaturated and methyl branched fatty acid and fatty alcohol
      chains. Part I. Synthesis.
AB  - Glycosyl dialkyl- and diacyl-glycerols bearing saturated, unsaturated or chiral
      methyl branched chains in the tail and disaccharide and trisaccharide
      carbohydrate headgroups were synthesised. Standard procedures were used for the
      preparation of the educts and the glyco lipids: trichloracetimidate procedure for
      the preparation of long-chained compounds, glycosylation using the beta
      peracetate and boron trifluoride etherate was successful for the preparation of
      lipids with a medium-alkyl chain length. Preparation of the ester was afforded in
      a multi-step synthesis according to published procedures. Thus, several lipids
      were synthesised in a few synthetic steps in good yields. The introduction of
      unsaturated or methyl branched chains lead to liquid crystallinity at ambient
      temperature, because these compounds will be used as model compounds for
      biological systems. The biophysical properties of these compounds will be
      reported in a following paper.

PMID- 15854622
TI  - Synthesis and mesomorphic properties of glycosyl dialkyl- and diacyl-glycerols
      bearing saturated, unsaturated and methyl branched fatty acid and fatty alcohol
      chains. Part II. Mesomorphic properties.
AB  - The biophysical properties of a series of glycosyl dialkyl- and diacyl-glycerols
      bearing unsaturated or chiral methyl branched chains in the tail, and di- and
      trisaccharide carbohydrate headgroups are described. Thermotropism was
      investigated by polarising microscopy, the lyotropism was investigated by small
      angle X-ray diffraction and by the contact preparation method, and the gel to
      liquid crystalline phase transition by FT-IR-spectroscopy. The compounds
      displayed thermotropic Smectic A (SmA), cubic and columnar phases, whereas in the
      lyotropic phase diagram lamellar, hexagonal and cubic phases are found. The
      introduction of unsaturated or methyl branched chains leads to liquid
      crystallinity at ambient temperature. The difference between the 1,3-oleyl
      glycerol maltoside and the corresponding 1,2-oleoyl-glycerol maltoside is small.

PMID- 15854623
TI  - The behaviour of beta-carotene in the phosphatidylcholine bilayer as revealed by
      a molecular simulation study.
AB  - A molecular dynamics (MD) simulation of the fully hydrated bilayer made of 1
      palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and containing beta-carotene (beta
      Car) molecules was carried out as a complementary approach to experimental
      techniques to investigate the orientation of beta-Car in the lipid membrane as
      well as its influence on the bilayer properties. The bilayer reached thermal
      equilibrium after 1200 ps of MD simulation and the productive run was carried out
      for 2800 ps. The results indicate that the carotene rings are located in the
      region occupied by the carbonyl groups of the POPC gamma-chain with no trace of
      penetration towards the centre of the bilayer. Carotene exhibits an ordering
      effect on both the beta- and the gamma-chain. While the fully saturated gamma
      chain is affected evenly along, the order of the mono-unsaturated beta-chain is
      modified mainly below the double bond. In general, a high value of the order
      parameter and the chain tilt in the range from 11.4 degrees to 26.7 degrees were
      observed for the beta-Car molecules. However, for chain segment adjacent to
      methyl groups the value of the order parameter is low and the tilt angle is close
      to 75 degrees . Moreover, the probability of trans conformation being generally
      close to 1.0 along the beta-Car chain is reduced for these segments. Our MD
      simulation study suggests two pools of the preferential orientation of beta-Car:
      a slightly bent structure corresponding to a small chain tilt angle and a rather
      stretched structure that corresponds to a higher chain tilt. The results are
      discussed in the light of experimental findings.

PMID- 15854624
TI  - Phosphatidylcholine structure determines cholesterol solubility and lipid
      polymorphism.
AB  - In the present work, we demonstrate that phosphatidylcholine with (16:1)9 acyl
      chains undergoes polymorphic rearrangements in mixtures with 0.6-0.8 mol fraction
      cholesterol. Studies were performed using differential scanning calorimetry, X
      ray diffraction, cryo-electron microscopy, 31P NMR static powder patterns and 13C
      MAS/NMR. Mixtures of phosphatidylcholine with (16:1)9 acyl chains and 0.6 mol
      fraction cholesterol, after being heated to 100 degrees C, can form an ordered
      array with periodicity 14 nm which may be indicative of a cubic phase. Our
      results indicate that the formation of highly curved bilayer structures, such as
      those required for membrane fusion, can occur in mixtures of cholesterol with
      certain phosphatidylcholines that do not form non-lamellar structures in the
      absence of cholesterol. We also determine the polymorphic behavior of mixtures of
      symmetric phosphatidylcholines with cholesterol. Species of phosphatidylcholine
      with (20:1)11, (22:1)13 or (24:1)15 acyl chains in mixtures with 0.6-0.8 mol
      fraction cholesterol undergo a transition to the hexagonal phase at temperatures
      70-80 degrees C. This is not the case for phosphatidylcholine with (18:1)6 acyl
      chains which remains in the lamellar phase up to 100 degrees C when mixed with as
      much as 0.8 mol fraction cholesterol. Thus, the polymorphic behavior of mixtures
      of phosphatidylcholine and cholesterol is not uncommon and is dependent on the
      intrinsic curvature of the phospholipid. Crystals of cholesterol can be detected
      in mixtures of all of these phosphatidylcholines at sufficiently high cholesterol
      mole fraction. What is unusual about the formation of these crystals in several
      cases is that cholesterol crystals are present in the monohydrate form in
      preference to the anhydrous form. Furthermore, after heating to 100 degrees C and
      recooling, the cholesterol crystals are again observed to be in the monohydrate
      form, although pure cholesterol crystals require many hours to rehydrate after
      being heated to 100 degrees C. Both the nature of the acyl chain as well as the
      mole fraction cholesterol determine whether cholesterol crystals in mixtures with
      the phospholipids will be in the monohydrate or in the anhydrous form.

PMID- 15854625
TI  - ATR-FTIR spectroscopy: a chemometric approach for studying the lipid organisation
      of the stratum corneum.
AB  - The barrier function of skin resides in the lipid components of the stratum
      corneum, particularly their spatial organisation. FTIR spectroscopy has already
      been used as a relevant tool to study this lipid organisation: IR vibration band
      shifts have been attributed to the variations in lipid organisation induced by
      temperature. Our study included a stratum corneum model, composed of the three
      main lipids: palmitic acid as an example of fatty acids, cholesterol and ceramide
      III as an example of ceramide. Different films with various ratios of these
      lipids were studied. In our analytical strategy, the interest of using a
      chemometric analysis of global data obtained from ATR-FTIR spectra to highlight
      the main interactions involved in the molecular organisation of lipids has been
      demonstrated. Two kinds of interaction between the three main lipids have been
      shown: a non polar interaction between the long hydrocarbon chains and a polar
      interaction as the hydrogen bonding between polar functional groups. By varying
      the lipid ratio, we have shown first that the relative importance of each
      interaction was modified, second, that the induced modification of organisation
      can be detected by chemometric analysis of the ATR-FTIR spectra. The role of each
      kind of lipid in the organisation has been discussed. In conclusion, associating
      the ATR-FTIR with chemometric treatment is a promising tool: firstly, to
      understand the consequence of lipid relative compositions on the structural
      organisation of the stratum corneum, secondly, to show the relationship between
      lipid organisation and percutaneous penetration data. Indeed, this methodology
      will be transposed to in vivo studies with IR measurements through a probe.

PMID- 15854626
TI  - The effect of cholesterol on the solubilization of phosphatidylcholine bilayers
      by the non-ionic surfactant Triton X-100.
AB  - Most of the studies on the solubilization of model membranes by Triton X-100 (TR)
      involve one lipid. The aim of the present study was to evaluate the effect of the
      addition of cholesterol on the solubilization of bilayers made of
      palmitoyloleoylphosphatidylcholine (POPC) or dipalmitoylphosphatidylcholine
      (DPPC). Detailed investigation of the kinetics of solubilization of the
      cholesterol-containing bilayers by TR at different temperatures reveals that: (i)
      At 4 degrees C, solubilization of both systems is relatively slow. Hence, in
      order to prevent misleading conclusions from turbidity measurements it is
      important to monitor the solubilization after steady-state values of optical
      density (OD) are reached. (ii) Studies of the temperature-induced changes of the
      aggregates present in mixtures of TR, POPC and cholesterol indicate that the
      state of aggregation at all temperatures (including 4 degrees C) represents
      equilibrium. By contrast, for DPPC/cholesterol/TR mixtures "kinetic traps" may
      occur not only at 4 degrees C but at higher temperatures as well (e.g. 37 degrees
      C). (iii) The presence of cholesterol in POPC bilayers makes the bilayers more
      resistant to solubilization at low temperatures, especially at 4 degrees C. As a
      consequence, the temperature dependence of the TR concentration required for
      complete solubilization (Dt(sol)) is no longer a monotonically increasing
      function (as for POPC bilayers) but a bell-shaped function, with a minimum at
      about 25 degrees C. Inclusion of cholesterol in DPPC bilayers makes the bilayers
      more resistant to solubilization at all temperatures except 4 degrees C. In this
      system, we observe a bell-shaped dependence of Dt(sol) on temperature, with a
      minimum at 37 degrees C. (iv) Both the rate of vesicle size growth and the rate
      of the solubilization of POPC vesicles are not affected by the inclusion of
      cholesterol in the bilayers. Similarly, cholesterol did not affect significantly
      the rate of size growth of DPPC bilayers at all temperatures, but reduced the
      rate of solubilization at 4 degrees C.

PMID- 15854627
TI  - Phase transitions in crystals of racemic long chain 2-amino alcohols.
AB  - Various techniques, namely differential scanning calorimetry, optical microscopy,
      dielectric and Raman spectroscopy, all covering a wide range of temperatures,
      were used to study the thermodynamically stable phases and molecular mobility of
      crystals of long chain 2-amino alcohols. The results showed that two different
      crystal forms are present in each sample. The temperature behaviour of the phases
      is studied in details.

PMID- 15854628
TI  - Phospholipid containing mixed micelles. Characterization of diheptanoyl
      phosphatidylcholine (DHPC) and sodium dodecyl sulfate and DHPC and dodecyl
      trimethylammonium bromide.
AB  - Mixed micelles of l,2-diheptanoyl-sn-grycero-3-phosphocholine (DHPC) with ionic
      detergents were prepared to develop well characterized substrates for the study
      of lipolytic enzymes. The aggregates that formed on mixing DHPC with the anionic
      surfactant sodium dodecyl sulfate (SDS) and with the positively charged dodecyl
      trimethylammonium bromide (DTAB) were investigated using time-resolved
      fluorescence quenching (TRFQ) to determine the aggregation numbers and
      bimolecular collision rates, and electron spin resonance (ESR) to measure the
      hydration index and microviscosity of the micelles at the micelle-water
      interface. Mixed micelles between the phospholipid and each of the detergents
      formed in all compositions, yielding interfaces with varying charge, hydration,
      and microviscosity. Both series of micelles were found to be globular up to 0.7
      mole fraction of DHPC, while the aggregation numbers varied within the same
      concentration range of the components less than 15%. Addition of the zwitterionic
      phospholipid component increased the degree of counterion dissociation as
      measured by the quenching of the fluorescence of pyrene by the bromide ions bound
      to DHPC/DTAB micelles, showing that at 0.6 mole fraction of DHPC 80% of the
      bromide ions are dissociated from the micelles. The interface water concentration
      decreased significantly on addition of DHPC to each detergent. For combined
      phospholipid and detergent concentration of 50 mM the interface water
      concentration decreased, as measured by ESR of the spin-probes, from 38.5 M/L of
      interface volume in SDS alone to 9 M/L when the phospholipid was present at 0.7
      mole fraction. Similar addition of DHPC to DTAB decreased the interfacial water
      concentration from 27 M/L to 11 M/L. Determination of the physicochemical
      parameters of the phospholipid containing mixed micelles here presented are
      likely to provide important insight into the design of assay systems for kinetic
      studies of phospholipid metabolizing enzymes.

PMID- 15854629
TI  - Contraceptive equity and access in the United States: a 2005 update.

PMID- 15854630
TI  - Safety and efficacy of Implanon, a single-rod implantable contraceptive
      containing etonogestrel.
AB  - OBJECTIVES: The safety and efficacy of a single-rod implantable contraceptive
      containing etonogestrel (Implanontrade mark) were investigated in a multicenter
      clinical trial. STUDY DESIGN: Sexually active American women (N=330) with
      apparently normal menstrual cycles used the implant for up to 2 years. All
      subjects recorded bleeding and/or spotting daily in a diary. Safety was assessed
      through adverse experiences (AEs), laboratory tests and physical and gynecologic
      examinations. RESULTS: Total exposure was 474 woman-years (6186 cycles), and 68%
      of subjects had at least 1 year of exposure. No pregnancies occurred. The most
      common bleeding pattern observed throughout the study was infrequent bleeding,
      defined as less than three episodes of bleeding in a reference period (excluding
      amenorrhea). The least common pattern was frequent bleeding, defined as more than
      five episodes of bleeding in a reference period. Infrequent, prolonged and
      frequent bleeding patterns were most common early in the study and declined
      thereafter. During the 3-month Reference Periods 2-8 (Months 4-24), the incidence
      of amenorrhea ranged from 14% to 20%. Forty-three subjects (13%) withdrew from
      the study because of bleeding pattern changes and 76 subjects (23%) discontinued
      because of other AEs. Other common AEs leading to discontinuation, besides
      bleeding irregularities, were emotional lability (6.1%), weight increase (3.3%),
      depression (2.4%) and acne (1.5%). Use of Implanon (etonogestrel subdermal
      implant, referred to herein as ENG implant) for up to 2 years had no clinically
      significant effects on laboratory parameters, physical and pelvic examinations,
      vital signs or body mass index. The average length of time required for ENG
      implant insertion and that for removal were 0.5 and 3.5 min, respectively, and
      all the procedures were uncomplicated. The return to normal menstrual cycles and
      fertility was rapid after removal. CONCLUSIONS: Implanon is a safe, highly
      effective and rapidly reversible new method of contraception.

PMID- 15854631
TI  - Medical abortion at 9-13 weeks' gestation: a review of 1076 consecutive cases.
AB  - OBJECTIVE: The aim of the study was to assess the use, efficacy and factors
      influencing the outcome of medical abortion at 9-13 weeks' gestation. METHODS:
      Retrospective chart review of consecutive women undergoing medical abortion at 9
      13 weeks' gestation was done. RESULTS: A total of 1927 abortions were carried out
      at 9-13 weeks' gestation, of which 1076 (55.8%) were undertaken medically.
      Efficacy decreased with increasing gestation (p=.02). Surgical evacuation was
      carried out in 45 (4.2%) women including 10 (2.7%) at 64-70 days, 11 (3.3%) at 71
      77 days, 10 (5.1%) at 78-84 days and 14 (8.0%) at 85-91 days of gestation
      (p=.02). Indications for surgery included continuing pregnancy [16 (1.5%) women],
      retained sac [5 (0.5%)], incomplete abortion [20 (1.9%)] and emergency curettage
      for bleeding [4 (0.4%)]. The number of misoprostol doses used and the induction
      to-abortion interval both significantly increased with gestation (p<.001), while
      analgesia requirements did not vary with increasing gestation (p=.18).
      CONCLUSIONS: Medical abortion at 9-13 weeks' gestation is an effective
      alternative to surgery. Medical methods should be offered routinely at these
      gestations, thus increasing women's choice.

PMID- 15854632
TI  - A pilot study of mifepristone and misoprostol administered at the same time for
      abortion up to 49 days gestation.
AB  - HYPOTHESIS: Simultaneous administration of mifepristone and misoprostol for
      medical abortion in women up to 49 days gestation will result in complete
      abortion in 90% of women within 24 h of treatment. MATERIALS AND METHODS: Forty
      women with pregnancies up to 49 days gestation inserted 800 mug vaginal
      misoprostol in our office immediately after taking mifepristone 200 mg orally.
      Follow-up visits, which included vaginal ultrasonography, occurred 24+/-1 h and 2
      weeks after treatment. If a gestational sac was still present at the first follow
      up visit, the misoprostol dose was repeated. Suction abortion was performed for a
      viable gestation at the second follow-up visit, presence of a nonviable gestation
      within 5 weeks of treatment and when clinically indicated. RESULTS: Expulsion
      occurred in 36/40 (90%, 95% CI 80-99) and 39/40 (98%, 95% CI 93-100) women by the
      first and second follow-up visits, respectively. One woman who had initially
      expelled the gestational sac after a single dose of misoprostol later required a
      suction curettage for an incomplete abortion. CONCLUSION: Simultaneous
      administration of mifepristone and vaginal misoprostol is a promising regimen for
      medical abortion up to 49 days gestation.

PMID- 15854633
TI  - Comparison of oral and vaginal misoprostol for cervical ripening before manual
      vacuum aspiration of first trimester pregnancy under local anesthesia: a
      randomized placebo-controlled study.
AB  - The objective of this prospective randomized placebo-controlled study was to
      determine the effectiveness of 400 mug oral and 400 mug vaginal misoprostol
      administration for cervical priming 3 h prior to manual vacuum aspiration (MVA)
      under local anesthesia for voluntary termination of pregnancy before 10 weeks of
      gestation in comparison with placebo oral or placebo vaginal administration (n=40
      in each group). Postmedication cervical dilatation was similar in the oral (mean,
      6.6+/-1.5) and vaginal (mean, 7.2+/-0.8) misoprostol groups but significantly
      higher compared with the oral (mean, 3.4+/-0.2) and vaginal (mean, 3.6+/-1.9)
      placebo groups. Duration of the procedure was also significantly shorter in the
      misoprostol groups in comparison with their placebo counterparts. Preoperative
      bleeding and side effects were more common in the misoprostol groups, but none
      required medical intervention. Intraoperative bleeding was less in the vaginal
      misoprostol group compared with the placebo groups. There was no significant
      difference in terms of visual analogue scores during the procedure, patient
      satisfaction, days of postoperative bleeding and rate of postoperative
      complications among the groups. Cervical priming with misoprostol administered
      orally or vaginally 3 h before MVA for termination of pregnancy under local
      anesthesia facilitates the procedure by decreasing the need for cervical
      dilatation and by shortening its duration without improving patients' pain
      perception and satisfaction mainly due to side effects.

PMID- 15854634
TI  - Labor induction abortion utilizing trilostane, a 3beta-hydroxysteroid
      dehydrogenase inhibitor.
AB  - Labor induction abortion in the second trimester is a difficult problem in
      developing countries because antiprogestins are either not available or
      unaffordable. When prostaglandins are used alone for labor induction abortion
      without antiprogestin pretreatment, the induction to delivery interval and the
      treatment failure rate increase. Trilostane, an inhibitor of 3beta-hydroxysteroid
      dehydrogenase enzyme system, was given to 93 women between 13 and 19 weeks
      gestation. The trilostane dosage used was 120 mg twice daily for the first 24 h,
      and then 240 mg twice daily for the next 24 h. The women returned after 48 h for
      hospital admission. The women were randomized to three different misoprostol
      regimens: low-dose vaginal group (200 microg every 4 h), high-dose vaginal group
      (initial dose of 400 microg followed by 200 microg every 4 h) and vaginal-oral
      group (400 microg vaginally followed by 200 microg orally every 4 h). The median
      induction to abortion times were 17, 8.3 and 9.4 h, respectively. The latter two
      groups had significantly shorter induction to delivery times (p<.05). The most
      common side effects were a burning feeling in the face (47.7%) and nausea
      (13.3%). Overall, trilostane side effects were mild and self-limiting and did not
      interfere with therapy. In conclusion, trilostane can be given as out-patient
      therapy prior to admission for prostaglandin administration in labor induction
      abortion.

PMID- 15854635
TI  - Different oral contraceptives and voice quality--an observational study.
AB  - The classical literature on endocrine effect on voice considers oral
      contraceptives (OCs) as a risk factor for voice. However, recent studies revealed
      no adverse effect of new-generation OCs on voice. It was also suggested that OCs
      could improve specific voice characteristics via different mechanisms. The aim of
      the present study was to evaluate the effect of OCs on voices of women who use
      different formulations containing drospirenone (n=10), desogestrel (n=9) and
      gestodene (n=10). Acoustic voice measures of the 29 women were evaluated twice
      during the menstrual cycle. Fundamental frequency, frequency as well as amplitude
      stability and noise characteristics were measured using a computerized voice
      analysis program. Results indicated that vocal stability and quality were similar
      in the three groups tested. Marginal differences were observed between the
      drospirenone group and the other two groups. This preliminary observational study
      indicates that although drospirenone was previously shown to reduce water
      retention, this effect was not found to directly influence voice characteristics
      of women who use OCs.

PMID- 15854636
TI  - Birth intervals and injectable contraception in sub-Saharan Africa.
AB  - OBJECTIVE: The interval between births is associated with child survival in the
      developing world. We aimed to investigate associations between use of depot
      medroxyprogesterone acetate and other reversible contraception and short birth
      intervals in sub-Saharan Africa. METHODS: Data from successive Demographic and
      Health Surveys undertaken in nine African countries were analyzed. Logistic
      regression was used to explain changes in the proportion of short birth intervals
      in four countries with relatively high use of reversible contraception. FINDINGS:
      The overall odds ratio for the trend was 0.90 (95% CI 0.84 to 0.95) and this was
      unaffected by adjusting for the other variables. The odds of a short birth
      interval were reduced by exclusive breastfeeding (OR 0.67, 95% CI 0.58 to 0.78)
      and increased by use of injectable contraception (OR 1.23, 95% CI 1.11 to 1.38).
      CONCLUSION: The proportion of short birth intervals has changed little over the
      last decade in a context of very low use of the intrauterine device. Widespread
      adoption of injectable contraception is associated with greater odds of a short
      birth interval, thus not contributing favorable conditions for improved child
      health.

PMID- 15854637
TI  - Distribution of a 3.5-mL (1.0%) C31G vaginal gel using magnetic resonance
      imaging.
AB  - C31G (Savvy) has been developed as a topical vaginal microbicide with broad
      spectrum antibacterial and antiviral properties. The objective of this study was
      to evaluate the distribution of a 1.0% concentration of (3.5 mL) C31G vaginal gel
      in the human pelvis using magnetic resonance imaging (MRI). Gel delivery with a
      standard applicator was primarily to the upper vagina and was well tolerated.
      Vaginal mucosal coverage at 18 min was excellent with 92% linear coverage and 75%
      surface contact coverage of the vagina. The upper vagina was almost completely
      covered and gel was also noted in the lower vagina. Coverage 6 h after
      application was substantially decreased, with 60% of maximal linear coverage and
      41% surface contact. There was a very minimal coverage of the vaginal mucosa
      noted 24 h following insertion. Simulated intercourse resulted in relatively
      little change in overall distribution at all three time points. Repeat
      application of the gel may be necessary if intercourse has not occurred within
      the first few hours after initial insertion.

PMID- 15854638
TI  - Effect of oral contraceptive treatment on bone mass acquisition in skeletally
      immature young female rats.
AB  - The objective of the present study was to investigate the effect of oral
      contraceptive (OC) treatment on bone mass accrual in skeletally immature young
      female rats. Animals in the baseline group were killed at the beginning of the
      experiment and were subjected to bone density assessment by peripheral
      quantitative computerized tomography (pQCT). The control group was fed a base
      diet free of phytoestrogens, while animals in the contraceptive group received
      the same base diet mixed with 2.67 microg desogestrel/100 g body weight and
      0.0533 microg ethinyl estradiol/100 g body weight. The duration of the treatment
      period was 16 weeks. Densitometric measurements by dual energy x-ray
      absorptiometry and serum bone markers assessment were carried out at baseline, at
      8 weeks and at 16 weeks, while pQCT densitometry took place after sacrifice. All
      bone mineral density and bone mineral content indices measured by dual energy x
      ray absorptiometry increased significantly throughout the study period in both
      the OC and control group. Concerning pQCT measurements, animals in both the OC
      and the control group had significantly higher cortical density compared with
      baseline (midtibia: p=.0003 and .0003, respectively). Total area and periosteal
      circumference were significantly higher in OC group, both in proximal (p=.003 and
      .003, respectively) and midtibia (p=.048 and .042, respectively) compared with
      baseline. Osteoprotegerin serum levels increased in both groups, and at the end
      of the experiment, circulating osteoprotegerin was significantly higher in the OC
      group compared with controls (p=.032). At the end of the experiment, carboxyl
      terminal telopeptides of collagen type I levels were significantly lower in the
      OC-treated animals compared with controls (p=.046). Our results suggest that OC
      administration to skeletally immature female rats allows normal bone accrual and
      may even improve bone geometry. This effect may be mediated through enhanced
      inhibition of bone resorption.

PMID- 15854639
TI  - A potent sperm motility-inhibiting activity of bioflavonoids from an
      ethnomedicine of Onge, Alstonia macrophylla Wall ex A. DC, leaf extract.
AB  - The methanol extract (ME) and the n-butanol fractions of methanolic extract of
      Alstonia macrophylla Wall ex A. DC leaves were investigated on the forward
      motility (FM) of mammalian (goat and human) spermatozoa. The ME at 600 microg mL
      1 as well as fraction B at 100 microg mL-1 concentrations showed marked
      inhibition of sperm FM in both goat and human species when tested by microscopic
      and spectrophotometric methods. Approximately 60-80% of the goat spermatozoa lost
      their FM when treated with 600 microg mL-1 of ME and 100 microg mL-1 of fraction
      B. At 100 microg mL-1 concentration, fraction B showed 90% loss of FM in human
      spermatozoa, while fraction B at 400 microg mL-1 concentration showed complete
      inhibition of sperm FM at 0 min. The inhibitory activity of fraction B increases
      with increasing concentration in a dose-dependent manner. Phytochemical study of
      the extract revealed that the leaf contains tannins, flavonoids, sterols,
      triterpenes, alkaloids and reducing sugars. Further fractionation and
      purification of the bioactive n-butanol part of ME showed the presence of ursolic
      acid (fraction B), beta-sitosterol (fraction A), beta-sitosterol glucoside and a
      mixture of minor compounds (fraction C, detected on thin-layer chromatography).
      The results reveal that fraction B (ursolic acid), a pentacyclic triterpene, has
      the potential of sperm motility inhibition and can serve as a topical vaginal
      contraceptive.

PMID- 15854640
TI  - Cyproterone acetate affects protamine gene expression in the testis of adult male
      rat.
AB  - The temporal effects of oral administration of cyproterone acetate (CPA), a
      progestational androgen receptor blocker, were studied on the fertility of adult
      male rat sires, at a dose of 20 mg kg-1 day-1 after 15 days of gavage. The
      treatment reduced the fertility and weights of accessory sex glands, without
      altering the serum levels of luteinizing hormone, follicle-stimulating hormone
      (FSH) and testosterone (T). Sperm counts were significantly reduced after
      treatment. Several changes were evident in caput epididymal sperm chromatin in
      treated rats. The in vitro decondensation rates of sperm chromatin and total
      fluorescent acridine orange (AO) dye uptake were enhanced. The fluorescent AO dye
      uptake by the double- and single-stranded sperm chromatin increased. The uptake
      of thiol-specific monobromobimane fluorescent dye by sperm chromatin was
      significantly reduced. Sperm of treated rats exhibited hypoprotamination.
      Protamine levels in the testis were significantly reduced after treatment.
      Androgen-binding protein (ABP) expression was significantly reduced in testis
      after treatment. A slight but significant increase was observed in cyclic AMP
      immunoexpression in testis after treatment. The expression and levels of
      transition proteins 1 (TP1) and 2 (TP2) as well as cyclic AMP response element
      modulator protein-tau were maintained at control levels in the testis of treated
      rats. The present study reports that androgen receptor occupation by CPA
      preferentially reduces the levels of spermatidal protamine in testis and
      spermatozoa involved in nuclear chromatin condensation. It is inferred that ABP
      could be mediating the effects of T in modulating the sequential expression of
      TPs and protamines during nuclear chromatin condensation. It is likely that
      indirect effects of T involve its aromatization in spermatids.

PMID- 15854641
TI  - A simple technique for localization of deeply inserted, nonpalpable Norplant
      implant.
AB  - Norplant removal may be complicated if deep insertion causes difficulty in
      localization with palpation. Various methods have been used to locate these
      deeply seated implants. Soft tissue X-ray films (standard anteroposterior and
      lateral views) with a paper clip placed as a marker by the clinician provide a
      simple method of locating deep implants.

PMID- 15854642
TI  - Same-day administration of depot-medroxyprogesterone acetate injection: a
      retrospective chart review.
AB  - A chart review of clients administered depot-medroxyprogesterone acetate (DMPA)
      injection in September of 2000 was performed to assess implementation of a same
      day injection administration protocol irregardless of menstrual cycle day. Women
      were classified into one of the three categories: (1) routine injection
      (injection given as specified by the package label), (2) same-day start injection
      (no injection for more than 6 months, did not meet labeled criteria for
      administration and received an injection the day of the visit) or (3) same-day
      restart injection (injection given within 6 months prior to receiving an
      injection at the visit despite being late for their injection). Of the 228 women
      receiving an injection, 104 (46%) had a nonroutine same-day injection, meaning
      almost half of the women receiving a contraceptive injection would have had to
      return for another visit if this protocol had not been in place. Among these
      women administered a same-day injection, 23 (22%) were also dispensed emergency
      contraception. Only 1 of the 104 women was subsequently identified to have become
      pregnant. Other pregnancies are presented to illustrate the importance of
      adherence to pregnancy testing at the time of injection and revisit, and the need
      for backup contraception. Using a same-day injection protocol, women can have
      increased access to injection contraception, and proper adherence to a protocol
      can assure few pregnancies.

PMID- 15854643
TI  - A quantitative description of the binding states and in vitro function of
      antitermination protein N of bacteriophage lambda.
AB  - The N protein of bacteriophage lambda activates transcription of genes that lie
      downstream of termination sequences by suppressing transcription termination. N
      binds to specific (boxB) and non-specific sites on the transcript RNA and
      contacts RNA polymerase via cis-RNA looping, resulting in "antitermination" of
      transcription. To find the effect of N-boxB binding on antitermination, we
      quantitatively relate binding measurements made in isolation to in vitro
      antitermination activity. We measure binding of N to boxB RNA, non-specific
      single-stranded RNA, and non-specific double-stranded DNA fluorimetrically, and
      use an equilibrium model to describe quantitatively the binding of N to nucleic
      acids of Escherichia coli transcription elongation complexes. We then test the
      model by comparison with in vitro N antitermination activity measured in
      reactions containing these same elongation complexes. We find that binding of N
      protein to the nucleic acid components of transcription elongation complexes can
      quantitatively predict antitermination activity, suggesting that antitermination
      in vitro is determined by a nucleic acid binding equilibrium with one molecule of
      N protein per RNA transcript being sufficient for antitermination. Elongation
      complexes contain numerous overlapping non-specific RNA and DNA-binding sites for
      N; the large number of sites compensates for the low N binding affinity, so
      multiple N proteins are expected to bind to elongation complexes. The
      occupancy/activity of these proteins is described by a binomial distribution of
      proteins on transcripts containing multiple non-specific sites. The contribution
      of specific (boxB) binding to activity also depends on this distribution.
      Specificity is not measured accurately by measurements made in the presence and
      in the absence of boxB. We find that antitermination is inhibited by non
      productive binding of N to non-specific sites on template DNA, and that NusA
      protein covers RNA sites on the transcript, limiting N access and activity. The
      activity and specificity of regulatory proteins that loop from high-affinity
      binding sites are likely modulated by multiple non-specific binding events; in
      vivo activity may also be regulated by the modulation of non-specific binding.

PMID- 15854644
TI  - Specific interactions between HIV-1 nucleocapsid protein and the TAR element.
AB  - During retroviral reverse transcription, the minus-strand strong-stop DNA (ss
      cDNA) is transferred to the 3' end of the genomic RNA and this requires the
      repeat (R) sequences present at both ends of the genome. In vitro, the human
      immunodeficiency virus type 1 (HIV-1) R sequence can promote DNA strand transfer
      when present in ectopic internal positions. Using HIV-1 model systems, the R
      sequences and nucleocapsid protein (NC) were found to be key determinants of ss
      cDNA transfer. To gain insights into specific interactions between HIV-1 NC and
      RNA and the influence of NC on R folding, we investigated the secondary
      structures of R in two natural contexts, namely at the 5' or 3' end of RNAs
      representing the terminal regions of the genome, and in two ectopic internal
      positions that also support efficient minus-strand transfer. To investigate the
      roles of NC zinc fingers and flanking basic domains in the NC/RNA interactions,
      we used NC mutants. Analyses of the viral RNA/NC complexes by chemical and
      enzymatic probings, and gel retardation assays were performed under conditions
      allowing ss-cDNA transfer by reverse transcriptase. We report that NC binds the
      TAR apical loop specifically in the four genetic contexts without changing the
      folding of the TAR hairpin and R region significantly, and this requires the NC
      zinc fingers. In addition, we show that efficient annealing of cTAR DNA to the 3'
      R relies on sequence complementarities between TAR and cTAR terminal loops. These
      findings suggest that the TAR apical loop in the acceptor RNA is the initiation
      site for the annealing reaction that is chaperoned by NC during the minus-strand
      transfer.

PMID- 15854645
TI  - Induction of inflammatory cytokines and interferon responses by double-stranded
      and single-stranded siRNAs is sequence-dependent and requires endosomal
      localization.
AB  - The potential induction of inflammatory cytokines and interferon responses by
      small-interfering RNAs (siRNAs) represents a major obstacle for their use as
      inhibitors of gene expression. Therapeutic applications of siRNAs will require a
      better understanding of the mechanisms that trigger such unwanted effects,
      especially in freshly isolated human cells. Surprisingly, the induction of tumor
      necrosis factor (TNF-alpha) and interleukin-6 (IL-6) in adherent peripheral blood
      mononuclear cells (PBMC) was not restricted to double-stranded siRNAs, because
      induction was also obtained with single-stranded siRNAs (sense or antisense
      strands). The immunostimulatory effects were sequence-dependent, since only
      certain sequences are prone to induce inflammatory responses while others are
      not. The induction of TNF-alpha, IL-6 and interferon alpha (IFN-alpha) was
      chloroquine-sensitive and dependent more likely on endosomal Toll-like receptor
      signaling in particular TLR8. Indeed, no significant immunostimulatory effects
      were detected when either double or single-stranded siRNAs were delivered
      directly to cytoplasm via electroporation. Both RNA types activated a NF-kappaB
      promoter-driven luciferase gene in transiently transfected human adherent PBMC.
      Moreover, culture of immature dendritic cells with either double or single
      stranded siRNAs stimulated interleukin-12 production and induced the expression
      of CD83, an activation marker. Interestingly, several double-stranded siRNAs did
      not induce TNF-alpha, IL-6 and IFN-alpha production, however, their single
      stranded sense or antisense did. Taken together, the present data indicate for
      the first time that the induction of inflammatory cytokines and IFN-alpha
      responses by either double-stranded or single-stranded siRNAs in adherent PBMC is
      sequence-dependent and requires endosomal intracellular signaling. The finding
      that endosomal localization of self-RNAs (sense strands) can trigger Toll-like
      receptor signaling in adherent human PBMC is intriguing because it indicates that
      endosomal self-RNAs can display a molecular pattern capable for activating innate
      immunity.

PMID- 15854646
TI  - Molecular basis of gyrase poisoning by the addiction toxin CcdB.
AB  - Gyrase is an ubiquitous bacterial enzyme that is responsible for disentangling
      DNA during DNA replication and transcription. It is the target of the toxin CcdB,
      a paradigm for plasmid addiction systems and related bacterial toxin-antitoxin
      systems. The crystal structure of CcdB and the dimerization domain of the A
      subunit of gyrase (GyrA14) dictates an open conformation for the catalytic domain
      of gyrase when CcdB is bound. The action of CcdB is one of a wedge that
      stabilizes a dead-end covalent gyrase:DNA adduct. Although CcdB and GyrA14 form a
      globally symmetric complex where the two 2-fold axes of both dimers align, the
      complex is asymmetric in its details. At the centre of the interaction site, the
      Trp99 pair of CcdB stacks with the Arg462 pair of GyrA14, explaining why the
      Arg462Cys mutation in the A subunit of gyrase confers resistance to CcdB.
      Overexpression of GyrA14 protects Escherichia coli cells against CcdB, mimicking
      the action of the antidote CcdA.

PMID- 15854647
TI  - Profound flanking sequence preference of Dnmt3a and Dnmt3b mammalian DNA
      methyltransferases shape the human epigenome.
AB  - Mammalian DNA methyltransferases methylate cytosine residues within CG
      dinucleotides. By statistical analysis of published data of the Human Epigenome
      Project we have determined flanking sequences of up to +/-four base-pairs
      surrounding the central CG site that are characteristic of high (5'-CTTGCGCAAG
      3') and low (5'-TGTTCGGTGG-3') levels of methylation in human genomic DNA. We
      have investigated the influence of flanking sequence on the catalytic activity of
      the Dnmt3a and Dnmt3b de novo DNA methyltransferases using a set of synthetic
      oligonucleotide substrates that covers all possible +/-1 flanks in quantitative
      terms. Methylation kinetics experiments revealed a >13-fold difference between
      the preferred (RCGY) and disfavored +/-1 flanking base-pairs (YCGR). In addition,
      AT-rich flanks are preferred over GC-rich ones. These experimental preferences
      coincide with the genomic methylation patterns. Therefore, we have expanded our
      experimental analysis and found a >500-fold difference in the methylation rates
      of the consensus sequences for high and low levels of methylation in the genome.
      This result demonstrates a very pronounced flanking sequence preference of Dnmt3a
      and Dnmt3b. It suggests that the methylation pattern of human DNA is due, in
      part, to the flanking sequence preferences of the de novo DNA MTases and that
      flanking sequence preferences could be involved in the origin of CG islands.
      Furthermore, similar flanking sequence preferences have been found for the
      stimulation of the immune system by unmethylated CGs, suggesting a co-evolution
      of DNA MTases and the immune system.

PMID- 15854648
TI  - Structural determinants of HIV-1 nucleocapsid protein for cTAR DNA binding and
      destabilization, and correlation with inhibition of self-primed DNA synthesis.
AB  - The nucleocapsid protein (NC) of human immunodeficiency virus type 1 (HIV-1) is
      formed of two highly conserved CCHC zinc fingers flanked by small basic domains.
      NC is required for the two obligatory strand transfers in viral DNA synthesis
      through its nucleic acid chaperoning properties. The first DNA strand transfer
      relies on NC's ability to bind and destabilize the secondary structure of
      complementary transactivation response region (cTAR) DNA, to inhibit self
      priming, and to promote the annealing of cTAR to TAR RNA. To further investigate
      NC chaperone properties, our aim was to identify by fluorescence spectroscopy and
      gel electrophoresis, the NC structural determinants for cTAR binding and
      destabilization, and for the inhibition of self-primed DNA synthesis on a model
      system using a series of NC mutants and HIV-1 reverse transcriptase. NC
      destabilization and self-priming inhibition properties were found to be supported
      by the two fingers in their proper context and the basic (29)RAPRKKG(35) linker.
      The strict requirement of the native proximal finger suggests that its
      hydrophobic platform (Val13, Phe16, Thr24 and Ala25) is crucial for binding,
      destabilization and inhibition of self-priming. In contrast, only partial folding
      of the distal finger is required, probably for presenting the Trp37 residue in an
      appropriate orientation. Also, Trp37 and the hydrophobic residues of the proximal
      finger appear to be essential for the propagation of the melting from the cTAR
      ends up to the middle of the stem. Finally, both N-terminal and C-terminal basic
      domains contribute to cTAR binding but not to its destabilization.

PMID- 15854649
TI  - Study of the mechanical properties of myomesin proteins using dynamic force
      spectroscopy.
AB  - Myomesin is the most prominent structural component of the sarcomeric M-Band that
      is expressed in mammalian heart and skeletal muscles. Like titin, this protein is
      an intracellular member of the Ig-fibronectin superfamily, which has a flexible
      filamentous structure and which is largely composed of two types of domain that
      are similar to immunoglobulin (Ig)-like and fibronectin type III (FNIII) domains.
      Several myomesin isoforms have been identified, and their expression patterns are
      highly regulated both spatially and temporally. Particularly, alternative
      splicing in the central part of the molecule gives rise to an isoform, EH
      (embryonic heart)-myomesin, containing a serine and proline-rich insertion with
      no well-defined secondary structure, the EH segment. EH-myomesin represents the
      major myomesin isoform at embryonic stages of mammalian heart and is rapidly down
      regulated around birth, but it is re-expressed in the heart of patients suffering
      from dilated cardio-myopathy. Here, in order to facilitate a better understanding
      of the physiological, and possibly pathological, functions of myomesin proteins,
      we explore the mechanical stability, elasticity and force-driven structural
      changes of human myomesin's sub-molecular segments using single-molecule force
      spectroscopy and protein engineering. We find that human myomesin molecules are
      composed of modules (Ig and FNIII), that are designed to withstand force and we
      demonstrate that the human cardiac EH segment functions like an additional
      elastic stretch in the middle part of the EH-myomesin and behaves like a random
      coil. Consequently myomesin isoforms (proteins with or without the EH segment)
      have different elastic properties, the EH-myomesin being the more compliant one.
      These findings imply that the compliance of the M-band increases with the amount
      of EH-myomesin it contains. So, we provide the evidence that not only titin but
      also other sarcomeric proteins have complicated visco-elastic properties
      depending on the contractile parameters in different muscle types.

PMID- 15854650
TI  - Structural insight into the dioxygenation of nitroarene compounds: the crystal
      structure of nitrobenzene dioxygenase.
AB  - Nitroaromatic compounds are used extensively in many industrial processes and
      have been released into the environment where they are considered environmental
      pollutants. Nitroaromatic compounds, in general, are resistant to oxidative
      attack due to the electron-withdrawing nature of the nitro groups and the
      stability of the benzene ring. However, the bacterium Comamonas sp. strain JS765
      can grow with nitrobenzene as a sole source of carbon, nitrogen and energy.
      Biodegradation is initiated by the nitrobenzene dioxygenase (NBDO) system. We
      have determined the structure of NBDO, which has a hetero-hexameric structure
      similar to that of several other Rieske non-heme iron dioxygenases. The catalytic
      subunit contains a Rieske iron-sulfur center and an active-site mononuclear iron
      atom. The structures of complexes with substrates nitrobenzene and 3-nitrotoluene
      reveal the structural basis for its activity with nitroarenes. The substrate
      pocket contains an asparagine residue that forms a hydrogen bond to the nitro
      group of the substrate, and orients the substrate in relation to the active-site
      mononuclear iron atom, positioning the molecule for oxidation at the nitro
      substituted carbon.

PMID- 15854651
TI  - Molecular recognition by a binary code.
AB  - Functional antibodies were obtained from a library of antigen-binding sites
      generated by a binary code restricted to tyrosine and serine. An antibody raised
      against human vascular endothelial growth factor recognized the antigen with high
      affinity (K(D)=60 nM) and high specificity in cell-based assays. The crystal
      structure of another antigen binding fragment in complex with its antigen (human
      death receptor DR5) revealed the structural basis for this minimalist mode of
      molecular recognition. Natural antigen-binding sites are enriched for tyrosine
      and serine, and we show that these amino acid residues are intrinsically well
      suited for molecular recognition. Furthermore, these results demonstrate that
      molecular recognition can evolve from even the simplest chemical diversity.

PMID- 15854652
TI  - Crystal structure and possible catalytic mechanism of microsomal prostaglandin E
      synthase type 2 (mPGES-2).
AB  - Prostaglandin (PG) H(2) (PGH(2)), formed from arachidonic acid, is an unstable
      intermediate and is converted efficiently into more stable arachidonate
      metabolites (PGD(2), PGE(2), and PGF(2)) by the action of three groups of
      enzymes. Prostaglandin E synthase catalyzes an isomerization reaction, PGH(2) to
      PGE(2). Microsomal prostaglandin E synthase type-2 (mPGES-2) has been
      crystallized with an anti-inflammatory drug indomethacin (IMN), and the complex
      structure has been determined at 2.6A resolution. mPGES-2 forms a dimer and is
      attached to lipid membrane by anchoring the N-terminal section. Two hydrophobic
      pockets connected to form a V shape are located in the bottom of a large cavity.
      IMN binds deeply in the cavity by placing the OMe-indole and chlorophenyl
      moieties into the V-shaped pockets, respectively, and the carboxyl group
      interacts with S(gamma) of C110 by forming a H-bond. A characteristic H-bond
      chain formation (N-H...S(gamma)-H...S(gamma)...H-N) is seen through Y107-C113
      C110-F112, which apparently decreases the pK(a) of S(gamma) of C110. The geometry
      suggests that the S(gamma) of C110 is most likely the catalytic site of mPGES-2.
      A search of the RCSB Protein Data Bank suggests that IMN can fit into the PGH(2)
      binding site in various proteins. On the basis of the crystal structure and
      mutation data, a PGH(2)-bound model structure was built. PGH(2) fits well into
      the IMN binding site by placing the alpha and omega-chains in the V-shaped
      pockets, and the endoperoxide moiety interacts with S(gamma) of C110. A possible
      catalytic mechanism is proposed on the basis of the crystal and model structures,
      and an alternative catalytic mechanism is described. The fold of mPGES-2 is quite
      similar to those of GSH-dependent hematopoietic prostaglandin D synthase, except
      for the two large loop sections.

PMID- 15854653
TI  - The structure of an antitumor C(H)2-domain-deleted humanized antibody.
AB  - C(H)2-domain-deleted CC49 (HuCC49DeltaCH2), a recombinant humanized antibody that
      recognizes the TAG-72 antigen expressed on a variety of human carcinomas, is
      secreted from cultured cells as a mixture of two homodimeric isoforms. Isoform A
      contains two covalent interchain disulfide bonds at heavy chain positions 239 and
      242, while isoform B fails to develop any interchain disulfide bonds but has 239
      242 intrachain disulfide bonds instead. Form A is currently in preclinical
      development as a therapeutic agent for treating colorectal carcinoma, though form
      B shows equal efficacy. HuCC49DeltaCH2 form B can be crystallized from sodium
      formate only in the presence of detergents. X-ray diffraction data were collected
      on a single cryo-cooled crystal grown with Triton X-100 and the structure was
      solved by molecular replacement. The model has refined to R=0.246 (R(free)=0.297)
      for 2.8A data. The antibodies pack in the crystal around crystallographic 2-fold
      axes as tetramers with approximate 222 symmetry. Atomic force microscopy studies
      show that this tetrameric structure is the crystal building block and also exists
      free in the mother liquor. The tetramer is composed of two rings, back-to-back,
      with a thickness of approximately 83A. Each ring is composed of two antibodies
      with the complementarity-determining regions (CDR) of the two Fabs of one
      antibody interacting with the CDR regions of the second antibody in a head-to
      head fashion. These rings are approximately 167A long and 112A wide. The C(H)3
      domain is inverted with respect to the Fabs when compared to the usual
      orientation found in conventional antibodies. The polypeptides joining the C(H)3
      domains to the Fab portions of the antibody are not seen and are almost certainly
      disordered. The antigen combining site of HuCC49DeltaCH2 is very similar, but not
      identical, in topology and charge distribution to that of antibody B72.3, which
      binds a similar epitope on TAG-72. The combining site consists of a deep cleft,
      heavily lined with aromatic amino acid side-chains but bounded by numerous
      charged groups.

PMID- 15854654
TI  - Trypsin inhibition by a peptide hormone: crystal structure of trypsin-vasopressin
      complex.
AB  - The large variety of serine protease inhibitors, available from various sources
      such as tissues, microorganisms, plants, etc., play an important role in
      regulating the proteolytic enzymes. The analysis of protease-inhibitor complexes
      helps in understanding the mechanism of action, as well as in designing
      inhibitors. Vasopressin, an anti-diuretic nonapeptide hormone, is found to be an
      effective inhibitor of trypsin, with a K(i) value of 5 nM. The crystal structure
      of the trypsin-vasopressin complex revealed that vasopressin fulfils all the
      important interactions for an inhibitor, without any break in the scissile
      peptide bond. The cyclic nature due to a disulfide bridge between Cys1 and Cys6
      of vasopressin provides structural rigidity to the peptide hormone. The trypsin
      binding site is located at the C terminus, while the neurophysin-binding site is
      at the N terminus of vasopressin. This study will assist in designing new peptide
      inhibitors. This study suggests that vasopressin inhibition of trypsin may have
      unexplored biological implications.

PMID- 15854655
TI  - Alternative IMP binding in feedback inhibition of hypoxanthine-guanine
      phosphoribosyltransferase from Thermoanaerobacter tengcongensis.
AB  - Crystal structures of Thermoanaerobacter tengcongensis hypoxanthine-guanine
      phosphoribosyltransferase (HGPRT) apoenzyme and the enzyme-inosine monophosphate
      (IMP) complex have been determined to 2.5A and 2.2A resolution, respectively. The
      active form of the enzyme was identified as a tetramer in solution and the K(i)
      value of IMP was measured to be 45 microM for alpha-D-phosphoribosyl-1
      pyrophosphate (PRPP). Conformation of the flexible loop in T.tengcongensis HGPRT,
      which is involved in substrate PRPP binding, is different from that observed in
      phosphoribosyltransferases (PRTs). It contains a 3-10 helix, and a unique double
      serine repeat. This loop is ordered even in the apoenzyme and assumes a half
      closed conformation. The primary magnesium ion is directly coordinated by side
      chains of Glu101 and Asp102, and water molecules in the apoenzyme, suggesting a
      possible prerequisite role for substrate PRPP binding. Most interestingly, an
      alternative IMP binding mode is found in the structure of T.tengcongensis HGPRT
      IMP complex. The 5'-phosphate of IMP occupies the PPi position usually seen in
      PRT-PRPP complexes. This new observation is consistent with the lower K(i) value
      of IMP and may suggest a mechanism involving multiple modes of interactions
      between IMP and T.tengcongensis HGPRT in product release and feedback inhibition.
      The structure of T.tengcongensis HGPRT is compared with those of mesophilic
      HPRTs, and several possible features contributing to its thermostability are
      elucidated. Overall, T.tengcongensis HGPRT appears to be more diverged from other
      PRTs.

PMID- 15854656
TI  - Structure of a full length psychrophilic cellulase from Pseudoalteromonas
      haloplanktis revealed by X-ray diffraction and small angle X-ray scattering.
AB  - Pseudoalteromonas haloplanktis is a psychrophilic Gram-negative bacterium
      isolated in Antarctica, that lives on organic remains of algae. This bacterium
      converts the cellulose, highly constitutive of algae, into an immediate nutritive
      form by biodegrading this biopolymer. To understand the mechanisms of cold
      adaptation of its enzymatic components, we studied the structural properties of
      an endoglucanase, Cel5G, by complementary methods, X-ray crystallography and
      small angle X-ray scattering. Using X-ray crystallography, we determined the
      structure of the catalytic core module of this family 5 endoglucanase, at 1.4A
      resolution in its native form and at 1.6A in the cellobiose-bound form. The
      catalytic module of Cel5G presents the (beta/alpha)(8)-barrel structure typical
      of clan GH-A of glycoside hydrolase families. The structural comparison of the
      catalytic core of Cel5G with the mesophilic catalytic core of Cel5A from Erwinia
      chrysanthemi revealed modifications at the atomic level leading to higher
      flexibility and thermolability, which might account for the higher activity of
      Cel5G at low temperatures. Using small angle X-ray scattering we further explored
      the structure at the entire enzyme level. We analyzed the dimensions, shape, and
      conformation of Cel5G full length in solution and especially of the linker
      between the catalytic module and the cellulose-binding module. The results showed
      that the linker is unstructured, and unusually long and flexible, a peculiarity
      that distinguishes it from its mesophilic counterpart. Loops formed at the base
      by disulfide bridges presumably add constraints to stabilize the most extended
      conformations. These results suggest that the linker plays a major role in cold
      adaptation of this psychrophilic enzyme, allowing steric optimization of
      substrate accessibility.

PMID- 15854657
TI  - Synergistic interactions between aqueous and membrane domains of a designed
      protein determine its fold and stability.
AB  - Membrane-spanning proteins contain both aqueous and membrane-spanning regions,
      both of which contribute to folding and stability. To explore the interplay
      between these two domains we have designed and studied the assembly of coiled
      coil peptides that span from the membrane into the aqueous phase. The membrane
      spanning segment is based on MS1, a transmembrane coiled coil that contains a
      single Asn at a buried a position of a central heptad in its sequence. This Asn
      has been shown to drive assembly of the monomeric peptide in a membrane
      environment to a mixture of dimers and trimers. The coiled coil has now been
      extended into the aqueous phase by addition of water-soluble helical extensions.
      Although too short to fold in isolation, these helical extensions were expected
      to interact synergistically with the transmembrane domain and modulate its
      stability as well as its conformational specificity for forming dimers versus
      trimers. One design contains Asn at a position of the aqueous helical extension,
      which was expected to specify a dimeric state; a second peptide, which contains
      Val at this position, was expected to form trimers. The thermodynamics of
      assembly of the hybrid peptides were studied in micelles by sedimentation
      equilibrium ultracentrifugation. The aqueous helical extensions indeed conferred
      additional stability and conformational specificity to MS1 in the expected
      manner. These studies highlight the delicate interplay between membrane-spanning
      and water-soluble regions of proteins, and demonstrate how these different
      environments define the thermodynamics of a given specific interaction. In this
      case, an Asn in the transmembrane domain provided a strong driving force for
      folding but failed to specify a unique oligomerization state, while an Asn in the
      water-soluble domain was able to define specificity for a specific aggregation
      state as well as modulate stability.

PMID- 15854658
TI  - Progress of structural genomics initiatives: an analysis of solved target
      structures.
AB  - The explosion in gene sequence data and technological breakthroughs in protein
      structure determination inspired the launch of structural genomics (SG)
      initiatives. An often stated goal of structural genomics is the high-throughput
      structural characterisation of all protein sequence families, with the long-term
      hope of significantly impacting on the life sciences, biotechnology and drug
      discovery. Here, we present a comprehensive analysis of solved SG targets to
      assess progress of these initiatives. Eleven consortia have contributed 316 non
      redundant entries and 323 protein chains to the Protein Data Bank (PDB), and 459
      and 393 domains to the CATH and SCOP structure classifications, respectively. The
      quality and size of these proteins are comparable to those solved in traditional
      structural biology and, despite huge scope for duplicated efforts, only 14% of
      targets have a close homologue (>/=30% sequence identity) solved by another
      consortium. Analysis of CATH and SCOP revealed the significant contribution that
      structural genomics is making to the coverage of superfamilies and folds. A total
      of 67% of SG domains in CATH are unique, lacking an already characterised close
      homologue in the PDB, whereas only 21% of non-SG domains are unique. For 29% of
      domains, structure determination revealed a remote evolutionary relationship not
      apparent from sequence, and 19% and 11% contributed new superfamilies and folds.
      The secondary structure class, fold and superfamily distributions of this dataset
      reflect those of the genomes. The domains fall into 172 different folds and 259
      superfamilies in CATH but the distribution is highly skewed. The most populous of
      these are those that recur most frequently in the genomes. Whilst 11% of
      superfamilies are bacteria-specific, most are common to all three superkingdoms
      of life and together the 316 PDB entries have provided new and reliable homology
      models for 9287 non-redundant gene sequences in 206 completely sequenced genomes.
      From the perspective of this analysis, it appears that structural genomics is on
      track to be a success, and it is hoped that this work will inform future
      directions of the field.

PMID- 15854659
TI  - Folding and stability of a primitive protein.
AB  - We have previously attempted to simulate domain creation in early protein
      evolution by recombining polypeptide segments from non-homologous proteins, and
      we have described the structure of one such de novo protein, 1b11, a segment
      swapped tetramer with novel architecture. Here, we have analyzed the
      thermodynamic stability and folding kinetics of the 1b11 tetramer and its
      monomeric and dimeric intermediates, and of 1b11 mutants with changes at the
      domain interface. Denatured 1b11 polypeptides fold into transient, folded
      monomers with marginal stability (DeltaG<1kcalmol(-1)) which convert rapidly (
      approximately 6x10(4)M(-1)s(-1)) into dimers (DeltaG=9.8kcal/mol) and then more
      slowly ( approximately 3M(-1)s(-1)) into tetramers (DeltaG=28kcalmol(-1)).
      Segment swapping takes place during dimerization, as suggested by mass
      spectroscopic analysis of covalently linked peptides derived from proteolysis of
      a disulfide-linked dimer. Our results confirm that segment swapping and
      associated oligomerization are both powerful ways of stabilizing proteins, and we
      suggest that this may have been a feature of early protein evolution.

PMID- 15854660
TI  - Rapid creation of a novel protein function by in vitro coevolution.
AB  - We have developed a simple and efficient method for creation of novel protein
      functions in an existing protein scaffold. The in vitro coevolution method
      involves design of a hypothetical pathway for the target function followed by
      stepwise directed evolution of the corresponding protein along the pathway. As a
      test case, this strategy was used to engineer variants of human estrogen receptor
      alpha ligand-binding domain (hERalphaLBD) with novel corticosterone activity. Two
      steroids, testosterone and progesterone, that provide a progressive structural
      bridge between 17beta-estradiol and corticosterone, were chosen to assist the
      directed evolution of hERalphaLBD. A total of approximately 10(6) variants were
      screened in four rounds of random mutagenesis, resulting in two hERalphaLBD
      variants that respond to corticosterone. Creation of this new ligand activity
      required the presence of four simultaneous mutations. In addition, several
      required mutations were located outside the ligand binding pocket and yet exerted
      important action on ligand binding. Our results demonstrate the ability of in
      vitro coevolution to create novel protein function that is difficult or
      impossible to achieve by existing protein engineering approaches and also shed
      light on the natural evolution of nuclear hormone receptors. This in vitro
      coevolution approach should provide a powerful, broadly applicable tool for
      engineering biological molecules and systems with novel functions.

PMID- 15854661
TI  - Are acidic and basic groups in buried proteins predicted to be ionized?
AB  - Ionizable residues play essential roles in proteins, modulating protein
      stability, fold and function. Asp, Glu, Arg, and Lys make up about a quarter of
      the residues in an average protein. Multi-conformation continuum electrostatic
      (MCCE) calculations were used to predict the ionization states of all acidic and
      basic residues in 490 proteins. Of all 36,192 ionizable residues, 93.5% were
      predicted to be ionized. Thirty-five percent have lost 4.08 kcal/mol solvation
      energy (DeltaDeltaG(rxn)) sufficient to shift a pK(a) by three pH units in the
      absence of other interactions and 17% have DeltaDeltaG(rxn) sufficient to shift
      pK(a) by five pH units. Overall 85% of these buried residues
      (DeltaDeltaG(rxn)>5DeltapK units) are ionized, including 92% of the Arg, 86% of
      the Asp, 77% of the Glu, and 75% of the Lys. Ion-pair interactions stabilize the
      ionization of both acids and bases. The backbone dipoles stabilize anions more
      than cations. The interactions with polar side-chains are also different for
      acids and bases. Asn and Gln stabilize all charges, Ser and Thr stabilize only
      acids while Tyr rarely stabilize Lys. Thus, hydroxyls are better hydrogen bond
      donors than acceptors. Buried ionized residues are more likely to be conserved
      than those on the surface. There are 3.95 residues buried per 100 residues in an
      average protein.

PMID- 15854662
TI  - A specific feature of the angiosperm Rab escort protein (REP) and evolution of
      the REP/GDI superfamily.
AB  - Rab GTPases participating in the regulation of vesicle trafficking in eukaryotes
      are geranylgeranylated by the Rab geranylgeranyl transferase (RabGGTase) in
      complex with the Rab escort protein (REP). Here, we describe basic properties of
      the Arabidopsis thaliana REP (AthREP), first REP outside yeasts or metazoans to
      be characterized. GFP-tagged AthREP, as well as the geranylgeranylation activity,
      were localized predominantly to the cytoplasm. Recombinant AthREP interacted with
      yeast 6His-Ypt1, tobacco 6His-RabA1a, and Arabidopsis RabA2a in vitro preferring
      the GDP-bound form of the latter. Recombinant AthREP with C-terminal but not N
      terminal tags stimulated geranylgeranylation of various Rab GTPases in
      Arabidopsis extracts in vitro. Neither recombinant AthREP protein exhibited
      activity in yeast extracts, while recombinant yeast REP (6His-SceMrs6) stimulated
      Rab geranylgeranylation in all extracts tested. We found that a conserved
      arginine residue, R195, known to be crucial for yeast REP function, is
      substituted by an asparagine or threonine residue in angiosperm REPs. A point
      mutant allele of AthREP with arginine at this position complemented the yeast REP
      mutation, while wild-type AthREP did not. Based on phylogenetic analysis of REP
      and GDP dissociation inhibitor (GDI) sequences from a broad range of eukaryotic
      lineages, we propose a new view on evolution of the REP/GDI superfamily with a bi
      functional REP/GDI protein as a direct ancestor.

PMID- 15854663
TI  - Upregulation of cyclooxygenase-II gene and PGE2 production of peritoneal
      macrophages in diabetic rats.
AB  - BACKGROUND: Patients with diabetes mellitus have increased risk of developing
      infectious complications following trauma and surgery. Recent studies have
      attributed altered immunoinflammatory responses of these patients as the cause of
      the underlying pathophysiology. This study was designed to investigate the effect
      of hyperglycemia on tissue-fixed macrophages (MO) PGE2 production. METHODS:
      Experimental hyperglycemia was induced in Sprague-Dawley rats by intraperitoneal
      injection of streptozotocin (65 mg/kg). Peritoneal MO were harvested and
      stimulated with Escherichia coli LPS (1 ng to 1 microg/ml). COX-2 mRNA expression
      was measured by RT-PCR with specific primers. PGE2 production by peritoneal MO
      was determined by ELISA. In addition, the effect of hyperglycemia on NFkappaB
      activation and pro-inflammatory cytokines induced by LPS were studied on RAW
      264.7 cells cultured in media with either 5.5 mm or 25 mm of glucose. RESULTS:
      LPS stimulation induced a dose-dependent response of PGE2 production and COX-2
      mRNA expression. MO from diabetic animals produced more COX-2 mRNA and PGE2 than
      the control animals. LPS stimulation induced NFkappaB activation that was
      attenuated by hyperglycemia in RAW cells. Similarly, hyperglycemia reduced the
      production of TNF and IL-6. CONCLUSIONS: Our data suggest that hyperglycemia
      alters LPS-stimulated macrophage responses by augmenting anti-inflammatory
      activities such as PGE2. In addition, hyperglycemia also reduces NFkappaB
      activity and NFkappaB-dependent cytokines production.

PMID- 15854664
TI  - Hemorrhagic shock-induced vascular hyporeactivity in the rat: relationship to
      gene expression of nitric oxide synthase, endothelin-1, and select cytokines in
      corresponding organs.
AB  - BACKGROUND: Our previous work observed that vascular hyporeactivity to
      norepinephrine (NE) developed after hemorrhage and the response was not the same
      in the 4 arteries examined. To evaluate possible mechanisms involved, the present
      study investigated the gene expression of iNOS, eNOS, IL-1beta, IL-6, TNF-alpha,
      and endothelin-1 in the corresponding organs, and the roles of nitric oxide (NO)
      and endothelin (ET). MATERIALS AND METHODS: LAnesthetized rats (n=7/time
      point/group) were hemorrhaged to a mean arterial pressure of 50 mmHg for 60 min.
      The vascular reactivity of the superior mesenteric (SMA), celiac (CA), left renal
      (LRA), and left femoral arteries (LFA) to NE was measured at baseline, at the end
      of the hypotensive period (E), and at 1, 2, and 4 h later in the three groups
      (hemorrhage, hemorrhage+NG-nitro-L-arginine methyl ester (L-NAME), an NO synthase
      inhibitor, or hemorrhage+PD142893, an ET receptor antagonist). Gene expression in
      ileum, left kidney, liver, and skeletal muscle was determined by quantitative RT
      PCR at these times. RESULTS: Vascular reactivity of SMA, CA, LRA, and LFA to NE
      decreased as much as 98% over 4 h compared with baseline. This loss of
      responsiveness in CA and LFA was more severe than in SMA and LRA. Gene expression
      of iNOS, eNOS, IL-1beta, IL-6, TNF-alpha, and endothelin-1 in the corresponding
      organs of select vasculatures increased markedly over baseline levels and the
      fold increase in mRNA levels of these enzymes and mediators in liver and skeletal
      muscle was higher than in ileum and left kidney. For example, at 4 h, iNOS
      expression was over 16-fold higher than baseline in liver and skeletal muscle,
      but 5- and 7-fold higher in ileum and kidney, respectively. L-NAME or PD142893
      partially attenuated the decreased vascular reactivity induced by hemorrhagic
      shock and attenuated the changes in gene expression observed. CONCLUSION: These
      findings suggest that the differential expression of NOS, cytokines, and
      endothelin-1 in different organs are associated with the development of vascular
      hyporeactivity after hemorrhagic shock and may account, at least in part, for the
      vascular bed diversity observed.

PMID- 15854665
TI  - The experimental agent pirfenidone reduces pro-fibrotic gene expression in a
      model of tacrolimus-induced nephrotoxicity.
AB  - BACKGROUND: Tacrolimus nephrotoxicity is thought to contribute to renal allograft
      dysfunction and subsequent failure, a process that is underpinned by alterations
      in mRNA expression of genes involved in matrix metabolism. The new anti-fibrotic
      pirfenidone was tested for its potential to reverse markers of renal dysfunction.
      MATERIALS AND METHODS: Rats were salt-depleted before tacrolimus and pirfenidone
      treatment. Serum creatinine, urinary protein/creatinine ratio, extracellular
      matrix deposition (ECM), and mRNA expression of genes involved in matrix turnover
      were assessed. RESULTS: Tacrolimus reduced TGF-beta mRNA expression below control
      levels and treatment with pirfenidone at all doses did not alter this effect.
      Likewise, TIMP-1 mRNA expression was depressed by the addition of tacrolimus and
      pirfenidone caused a further decrease in expression. Collagen III, MMP-2, and MMP
      9 expression was unchanged by tacrolimus, but pirfenidone reduced collagen III
      below control levels. ECM was slight (1-4%) and not significantly different
      between groups. CONCLUSIONS: These findings suggest that pirfenidone can
      attenuate the limited fibrotic potential of tacrolimus.

PMID- 15854666
TI  - Clinical evaluation of circulating interleukin-6 and interleukin-10 levels after
      surgery-induced inflammation.
AB  - BACKGROUND: It was previously reported that both pro- and anti-inflammatory
      cytokines are elevated in systemic inflammatory response syndrome (SIRS).
      Cytokine-mediated systemic neutrophil activation is a direct consequence of SIRS,
      and can lead to multiple organ dysfunction syndrome (MODS). This prospective
      study assessed the risk of SIRS and MODS after orthognathic surgery by measuring
      the circulating levels of inflammatory cytokines such as IL-6 and IL-10 as well
      as the neutrophil functions as a marker of organ failure. MATERIALS AND METHODS:
      Blood samples for the measurement of IL-6, IL-10, CRP, neutrophil counts, and
      neutrophil function were drawn from 21 patients with mandibular prognathism at 2
      days before, and at 1 and 3 days after orthognathic surgery. The neutrophil
      function was estimated by superoxide production and elastase release under the
      stimulation of FMLP. RESULTS: Eight of the 21 patients were applicable to SIRS
      criteria 1 day postoperatively, and all of the subjects were excluded from SIRS
      criteria 3 days postoperatively. Although IL-6 and IL-10 levels were raised 1 day
      postoperatively, increased cytokine concentrations were decreased in most
      patients at 3 days postoperatively. The IL-6 concentration and the ratio of IL-6
      to IL-10 were higher in the SIRS-matched group compared with the non-SIRS-matched
      group. Neutrophil priming for superoxide production and elastase release was
      discovered 1 day after orthognathic surgery, and differences in those values
      could not be distinguished between the groups. CONCLUSIONS: These results suggest
      that a few patients in whom high levels of circulating inflammatory cytokine and
      neutrophil-derived toxic factor continue may have a possibility of contracting
      severe diseases such as SIRS and MODS after orthognathic surgery. We conclude
      that the ratio of IL-6 to IL-10 may be a predictive factor in SIRS.

PMID- 15854667
TI  - Expression of TGF-beta1 in smooth muscle cells regulates endothelial progenitor
      cells migration and differentiation.
AB  - OBJECTIVE: Endothelial angiogenesis in the intima of the arterial wall is one of
      key events in the pathogenesis of arteriosclerosis. The molecular mechanisms by
      which transforming growth factor beta 1 (TGFbeta1) and endothelial progenitor
      cells may be responsible for angiogenesis of arteriosclerosis lesions are poorly
      understood. MATERIALS AND METHODS: Primary culture smooth muscle cells were
      transfected with pMAMneoTGFbeta1. ELISA checked VEGF expression in smooth muscle
      cells. Human EPCs (CD34+ cells) were cultured in pMAMneoTGFbeta1 or pMAMneo
      transfected smooth muscle cells conditional medium. After 21 days, differentiated
      endothelial colonies were confirmed by immunofluorescence for von Willebrand
      factor (vWF) and vascular-endothelial (VE)-cadherin. The VEGFR-1 expression in
      differentiated endothelial colonies was detected by ELISA. Cells migration and
      adhesion toward pMAMneoTGFbeta1 and pMAMneo transfected smooth muscle cells were
      also measured in parallel flow chamber. RESULTS: Abundant TGFbeta1 stable
      expressed in smooth muscle cells. TGFbeta1 transfected smooth muscle cells
      expressed significantly higher level VEGF than pMAMneo group. As judged by
      positive staining for endothelial markers vWF and VE-cadherin, the combination of
      TGFbeta1 transfected smooth muscle cells conditional medium produced
      significantly more endothelial colonies (P<0.05) than did pMAMneo group. The
      adhesion force between endothelial progenitor cells and smooth muscle cells in
      TGFbeta1 group was higher than control. CONCLUSION: TGFbeta1 expressed smooth
      muscle cells can be helpful for increasing endothelial progenitor cells adhesion
      and differentiation. It may be responsible for angiogenesis of arteriosclerosis
      lesions and useful for blood vessel tissue engineering.

PMID- 15854668
TI  - Regional differences of melphalan lung levels after isolated lung perfusion in
      the rat.
AB  - BACKGROUND: Efficacy studies of isolated lung perfusion (ILuP) with melphalan
      showed superior results compared to intravenous therapy. However, the influence
      of pharmacokinetic parameters on the final melphalan lung concentration (FMLC) is
      unknown. In this study, we studied the impact of three different perfusion
      parameters on the FMLC in different areas of the lung. MATERIAL AND METHODS:
      Fifty-four rats were randomized into nine groups. Each group underwent ILuP with
      variation of perfusion duration (15, 30, and 60 min), the flow (0.125, 0.25, and
      0.5 ml/min), concentration (8.3, 16.7, 33.3, 66.7, and 133.3 microg/ml) and the
      resulting dose (maximum 4 mg/kg). Lung samples were taken from the hilum and at
      the periphery of the lung (apex, base). Additional samples were taken to evaluate
      wet-to-dry ratio (W/D-ratio). Multiple linear regression and Student's t test
      were used for analysis. Significance was defined as a P<or=0.05. RESULTS:
      Experiment 1: The W/D-ratio was not influenced by varying the perfusion
      parameters (P=0.97). Experiment 2: multiple regression led to an equation that
      predicts FMLC for each area of the lung studied. FMLC is dependent on
      concentration, perfusion time, and region. CONCLUSION: The influence of the
      perfusion parameters on FMLC is dependent on the area of the lung perfused. This
      should be taken into consideration when pulmonary metastases are treated with
      ILuP.

PMID- 15854669
TI  - Evaluation of an absorbable cyanoacrylate adhesive as a suture line sealant.
AB  - BACKGROUND: Previous formulations of cyanoacrylate, though very effective, proved
      to have too high a tissue reactivity to be used internally. A novel cyanoacrylate
      compound with less tissue reactivity was recently developed. The objective of
      this study was to assess this novel cyanoacrylate compound for the use as
      vascular suture line sealant. MATERIALS AND METHODS: Twelve adult female sheep
      received a 6 mm PTFE interposition graft in each iliac artery, for a total of 24
      grafts. Using oxidized cellulose (Surgicel) as a control, two formulations of a
      new cyanoacrylate compound (named "compound A" and "compound B") were assessed
      during this trial. Hemostatic efficiency was measured at the time of operation by
      the assessment of bleeding time and amount of blood loss. Long-term graft patency
      was assessed angiographically at 4, 6, and 18 months. Tissue reaction at 2 weeks,
      1, 6, and 18 months was assessed grossly by vascular surgeons and microscopically
      by a blinded pathologist. RESULTS: Average time to hemostasis was 37.6, 50.6, and
      219 s in group A, group B, and oxidized cellulose control groups, respectively
      (P<or=0.001 for both compounds versus control). There were no significant
      differences between groups with regards to graft patency. Histopathology analysis
      demonstrated mild to moderate tissue reaction at 2 weeks and 1 month in the
      cyanoacrylate groups compared with controls at 1 month (ANOVA P=0.004). Mild
      tissue reaction was seen at 6 months and 18 months, with no significant
      differences between groups (ANOVA P=0.08, 0.62, respectively). CONCLUSIONS: The
      novel cyanoacrylate compound examined in this study is a highly effective suture
      line sealant with only mild tissue reactivity and no significant effects on graft
      patency when studied over an 18 month period.

PMID- 15854670
TI  - Is the preconditioning threshold different in females?
AB  - BACKGROUND: Preconditioning is injury induced protection against subsequent
      insult. Studies have shown that both males and females may be preconditioned.
      Females appear to have an innate cardioprotection, therefore, we hypothesized
      that the preconditioning threshold may differ between males and females.
      MATERIALS AND METHODS: Male and female rats were divided into five groups (n=4
      9). Animals were given an intraperitoneal (i.p.) injection of 125, 250, or 500
      micrograms/kilogram Salmonella typhimurium lipopolysaccharide (ETX) or 0.4-ml
      normal saline (NS). After 24-h incubation another i.p. injection of either 500
      micrograms/kilogram ETX (injury dose) or NS was given and the animals incubated
      an additional 6 h. Shams received two injections of NS. Non-preconditioned rats
      (PC-) received NS followed by ETX. Preconditioned rats had i.p. injections of 125
      mug/kg ETX (PC +125), 250 microg/kg ETX (PC +250), or 500 microg/kg ETX (PC +500)
      followed by the injury dose ETX. The rats were then anesthetized and myocardial
      function evaluated with the Langendorff perfusion model. RESULTS: PC +500 females
      were preconditioned and were able to maintain cardiac function similar to shams.
      Conversely, PC +125 females were not preconditioned with this stimulus and had a
      significant decrease in cardiac function similar to PC- rats. Male PC +500 and PC
      +125 rats, however, retained cardiac function comparable to shams, while PC-
      males showed a significant decrement. CONCLUSIONS: Males and females may each be
      preconditioned by endotoxin; however, the preconditioning threshold is higher in
      females than males.

PMID- 15854671
TI  - A GM-CSF/CD40L producing cell augments anti-tumor T cell responses.
AB  - BACKGROUND: Tumors evade T cell-mediated rejection despite the presence of tumor
      associated antigens (TAAs) and T cells specific for these TAAs in cancer
      patients. Therapeutic tumor vaccines are being developed to prevent this evasion.
      Previous reports revealed that anti-tumor T cell responses could be activated in
      mice when granulocyte macrophage-colony stimulating factor (GM-CSF) or CD40L are
      produced at tumor vaccine sites. We sought to test the hypothesis that production
      of GM-CSF and CD40L by a bystander cell line could induce an anti-tumor T cell
      response in an in vitro human model. MATERIALS AND METHODS: The K562 cell line
      was stably transfected with the human GM-CSF and CD40L genes. The effect of this
      cell line on T cell responses was tested in a human autologous mixed tumor
      cell/lymph node cell model using tissue from a series of cancer patients.
      RESULTS: There was no significant anti-tumor T cell response when human
      lymphocytes derived from tumor-draining lymph nodes were stimulated with
      autologous tumor cells in vitro. However, significant anti-tumor T cell responses
      were observed when bystander cells transfected with CD40L and GM-CSF were added
      to the cultures. CONCLUSIONS: A fully autologous human model consisting of tumor
      cells as stimulator cells and tumor-draining lymph nodes as responder cells can
      be used to test immunotherapeutic strategies. T cells in these lymph nodes are
      unresponsive to autologous tumor cells, but this lack of responsiveness can be
      reversed in the presence of GM-CSF and CD40L. These data provide a rationale for
      testing tumor cell vaccines incorporating GM-CSF- and CD40L-expressing bystanders
      in clinical trials.

PMID- 15854672
TI  - Do preservation solutions protect rat cremaster microcirculation during ischemia
      and reperfusion?
AB  - BACKGROUND: Our aim was to investigate the potential of the preservation solution
      Celsior to protect rat cremaster muscle microcirculation during ischemia and
      reperfusion, and to compare its effects with those of HTK (histidine-tryptophan
      ketoglutarate-Bretschneider solution). Because of its anti-oxidant contents, we
      expected Celsior to be more protective than HTK. MATERIALS AND METHODS: Capillary
      perfusion and leukocyte-endothelium interactions were examined in rat cremaster
      muscle using intravital microscopy. After perfusion with Celsior or HTK (4
      degrees C), the cremaster was subjected to 4 or 6 h of warm (33-34 degrees C)
      ischemia and 2 h of reperfusion. Measurements were performed prior to perfusion
      and/or ischemia, and 0, 1, and 2 h after restoration of flow. RESULTS: Without
      Celsior or HTK, capillary perfusion transiently decreased to 50% of baseline
      after 4 h of ischemia; it remained low (45%) after 6 h of ischemia. Whereas HTK
      had no significant influence, Celsior deteriorated capillary perfusion: it
      remained low after 4 h of ischemia (39-48%) and decreased even further after 6 h
      of ischemia (18-8%). Both preservation solutions similarly reduced the increase
      in leukocyte-endothelium interactions after ischemia. CONCLUSIONS: Preischemic
      tissue perfusion with Celsior had an adverse effect on capillary perfusion in rat
      cremaster muscle after 4 and 6 h of ischemia, whereas HTK did not significantly
      influence this parameter. Both preservation solutions similarly prevented the
      increase in leukocyte-endothelium interactions after ischemia. These data suggest
      that HTK is more suited as a preservation solution for muscular tissue than
      Celsior, especially when the known protective effects of HTK on muscle function
      are taken into account.

PMID- 15854673
TI  - New molecular concepts of Barrett's esophagus: clinical implications and
      biomarkers.
AB  - Barrett's esophagus (BE) represents the most serious histological consequence of
      gastroesophageal reflux disease (GERD) that develops in 5-10% of patients with
      GERD. Given that BE is the only known precursor to esophageal adenocarcinoma
      (EA), a systematic endoscopic biopsy protocol can detect EAs at an early stage.
      However, endoscopic and histopathological evaluation of BE are not adequate for
      effective screening of high risk patients. Therefore, molecular abnormalities
      associated with BE have been considered as surrogate markers and their use as
      such is proposed. Flow cytometry is the most useful adjunct to histology, and
      ploidy status of BE is an independent risk factor. Cyclin D1 overexpression is
      inversely correlated with survival in EA. C-erbB2 (+) patients have poorer
      prognosis. High plasma adenomatous polyposis coli levels correlate with reduced
      patient survival. p53 expression allows patient risk for EA stratification.
      Nuclear factor-kappaB overexpression inversely correlates with good response to
      adjuvant chemotherapy and radiotherapy in EA. Patients with cyclooxygenase-2
      overexpression have reduced survival rates. Increased E-cadherin staining is
      associated with shorter survival in EA patients who received chemoradiotherapy.
      Finally, existing data cannot rule out a correlation between EA and colorectal
      tumors. Seventeen BE molecular alterations yielded noteworthy clinical
      implications. Apart from endoscopy and histology, these data allow for better
      risk stratification for patients with BE and for more efficient and timely
      therapeutic approaches.

PMID- 15854674
TI  - A physiological model of cerebral blood flow control.
AB  - The construction of a computational model of the human brain circulation is
      described. We combine an existing model of the biophysics of the circulatory
      system, a basic model of brain metabolic biochemistry, and a model of the
      functioning of vascular smooth muscle (VSM) into a single model. This represents
      a first attempt to understand how the numerous different feedback pathways by
      which cerebral blood flow is controlled interact with each other. The present
      work comprises the following: Descriptions of the physiology underlying the
      model; general comments on the processes by which this physiology is translated
      into mathematics; comments on parameter setting; and some simulation results. The
      simulations presented are preliminary, but show qualitative agreement between
      model behaviour and experimental results.

PMID- 15854675
TI  - The structural identifiability of the susceptible infected recovered model with
      seasonal forcing.
AB  - In this paper, it is shown that the SIR epidemic model, with the force of
      infection subject to seasonal variation, and a proportion of either the
      prevalence or the incidence measured, is unidentifiable unless certain key system
      parameters are known, or measurable. This means that an uncountable number of
      different parameter vectors can, theoretically, give rise to the same idealised
      output data. Any subsequent parameter estimation from real data must be viewed
      with little confidence as a result. The approach adopted for the structural
      identifiability analysis utilises the existence of an infinitely differentiable
      transformation that connects the state trajectories corresponding to parameter
      vectors that give rise to identical output data. When this approach proves
      computationally intractable, it is possible to use the converse idea that the
      existence of a coordinate transformation between states for particular parameter
      vectors implies indistinguishability between these vectors from the corresponding
      model outputs.

PMID- 15854676
TI  - Turing instability in pioneer/climax species interactions.
AB  - Systems of pioneer and climax species are used to model interactions of species
      whose reproductive capacity is sensitive to population density in their shared
      ecosystem. Intraspecies interaction coefficients can be adjusted so that
      spatially homogeneous solutions are stable to small perturbations. In a reaction
      diffusion pioneer/climax model we will determine the critical value of the
      diffusion rate of the climax species, below which the equilibrium solution is
      unstable to non-homogeneous perturbations. For diffusion rates smaller than this
      critical value, an equilibrium solution remains stable to spatially homogeneous
      perturbations but is unstable to non-homogeneous perturbations. A Turing
      (diffusional) bifurcation leads to the formation of spatial patterns in species'
      densities. Forcing, interpreted as stocking or harvesting of the species, can
      reverse the bifurcation and establish equilibrium solutions which are stable to
      small perturbations. The implicit function theorem is used to determine whether
      stocking or harvesting of one of the species in the model is the appropriate
      remedy for diffusional instability. The use of stocking or harvesting by a
      natural resource manager thus influences the long-term dynamics and spatial
      distribution of species in a pioneer/climax ecosystem.

PMID- 15854677
TI  - Modeling the simple epidemic with deterministic differential equations and random
      initial conditions.
AB  - In a simple epidemic the only transition in the population is from susceptible to
      infected and the total population size is fixed for all time. This paper
      investigates the effect of random initial conditions on the deterministic model
      for the simple epidemic. By assuming a Beta distribution on the initial
      proportion of susceptibles, we define a distribution that describes the
      proportion of susceptibles in a population at any time during an epidemic. The
      mean and variance for this distribution are derived as hypergeometric functions,
      and the behavior of these functions is investigated. Lastly, we define a
      distribution to describe the time until a given proportion of the population
      remains susceptible. A method for finding the quantiles of this distribution is
      developed and used to make confidence statements regarding the time until a given
      proportion of the population is susceptible.

PMID- 15854678
TI  - An operator splitting method for solving the bidomain equations coupled to a
      volume conductor model for the torso.
AB  - In this paper we present a numerical method for the bidomain model, which
      describes the electrical activity in the heart. The model consists of two partial
      differential equations (PDEs), which are coupled to systems of ordinary
      differential equations (ODEs) describing electrochemical reactions in the cardiac
      cells. Many applications require coupling these equations to a third PDE,
      describing the electrical fields in the torso surrounding the heart. The
      resulting system is challenging to solve numerically, because of its complexity
      and very strict resolution requirements in time and space. We propose a method
      based on operator splitting and a fully coupled discretization of the three PDEs.
      Numerical experiments show that for simple simulation cases and fine
      discretizations, the algorithm is second-order accurate in space and time.

PMID- 15854679
TI  - Hemolymph coagulation and phenoloxidase in Drosophila larvae.
AB  - Hemolymph coagulation is a first response to wounding in insects. Although
      studies have been performed in large-bodied insects such as the moth Galleria
      mellonella, less is known about clotting in Drosophila melanogaster, the insect
      most useful for genetic and molecular analyses of innate immunity. Here we show
      the similarities between clots in Drosophila and Galleria by light- and electron
      microscopy. Phenoloxidase changes the Drosophila clot's physical properties
      through cross-linking and melanization, but it is not necessary for preliminary
      soft clot formation. Bacteria associate with the clot, but this alone does not
      necessarily kill them. The stage is now set for rapid advances in our
      understanding of insect hemolymph coagulation, its roles in immune defense and
      wound healing, and for a more comprehensive grasp of the insect immune system in
      general.

PMID- 15854680
TI  - Localization and bacteriostasis of Vibrio introduced into the Pacific white
      shrimp, Litopenaeus vannamei.
AB  - Although numerous mechanisms of immune defense have been described in
      crustaceans, the tissue distribution and fate of live bacteria introduced into
      the host remain unclear. In the present study, Litopenaeus vannamei were injected
      with a sub-lethal dose of kanamycin-resistant Vibrio campbellii expressing green
      fluorescent protein. Accumulation of intact bacteria was quantified by real-time
      PCR, while bacteriostasis was quantified as the percentage of intact bacteria
      that could not be recovered by selective plating. Over the 240 min examined, the
      lymphoid organ contained the greatest number of intact V. campbellii per gram
      tissue as well as the lowest percentage of culturable V. campbellii compared to
      other tissues, including the hemolymph. In contrast, the gills and hepatopancreas
      accumulated intact bacteria, but contained a significantly greater percentage of
      culturable bacteria than the hemolymph after 240 min. These data suggest that the
      lymphoid organ plays a major role in bacterial uptake and bacteriostasis in
      penaeid shrimp.

PMID- 15854681
TI  - Molecular cloning and characterization of two types of CD8alpha from ginbuna
      crucian carp, Carassius auratus langsdorfii.
AB  - We cloned and sequenced full-length cDNAs for two types of CD8alpha from the S3n
      strain of ginbuna crucian carp (Carassius auratus langsdorfii) and quantified the
      expression of CD8alpha genes after sensitization by scale grafting, employing a
      model system of clonal triploid ginbuna and tetraploid ginbuna-goldfish hybrids.
      RT-PCR yielded four different fragments of CD8alpha homologue from the S3n strain
      of ginbuna and these sequences were classified into two groups. The two types of
      ginbuna CD8alpha (gbCD8alpha) were also found in other strains of triploid
      ginbuna and goldfish, which are a subspecies of ginbuna. The gbCD8alpha chains
      consisted of a signal peptide, Ig superfamily (IgSf) V-like domain, hinge,
      transmembrane domain, and cytoplasmic domain similar to other known CD8alpha.
      Phylogenetic analysis indicated that both types of gbCD8alpha are closely related
      to CD8alpha from other vertebrates. Expression of both types of gbCD8alpha mRNA
      was detected in the gill, thymus, head kidney, posterior kidney, spleen,
      intestine and peripheral blood leucocytes. In addition, quantitative real-time
      PCR analysis demonstrated that copy numbers of both gbCD8alpha gene products in
      kidney cells increased significantly following grafting with allogeneic but not
      isogeneic scales, and that regulation of expression correlated with that of
      TCRbeta. Expression of both gbCD8alpha genes after second scale allografting was
      elevated compared to that after the first set of grafting. These results suggest
      that expression analysis of these two gbCD8alpha sequences provides a useful tool
      to address the involvement of cytotoxic T-lymphocytes during the cell-meditated
      immune response in fish.

PMID- 15854682
TI  - The opsonising activity of a pentraxin-like protein isolated from snapper (Pagrus
      auratus, Sparidae) serum.
AB  - In mammals the pentraxins, C-reactive protein (CRP) and serum amyloid P component
      (SAP) are important components of the immune response. Although pentraxins have
      been isolated from a number of fish species few studies detail their functional
      immunological role. In this paper we report the establishment of a flow cytometry
      based assay to measure the phagocytic activity of isolated snapper head kidney
      leukocytes (HKLs). This assay was then used to examine the ability of a pentraxin
      like protein isolated from the serum of snapper (P. auratus) (Sn-PLP) to act as
      an opsonin. Incubation of snapper head kidney leukocytes (HKL) with FITC-labelled
      beads resulted in uptake of these particles by approximately 35% of HKLs.
      Incubation of beads with Sn-PLP enhanced phagocytosis by snapper HKLs in a dose
      dependant manner. Enhanced phagocytosis could be inhibited by addition of a
      rabbit anti-Sn-PLP antibody suggesting that Sn-PLP may act as a ligand for a HKL
      cell surface receptor. This study provides further evidence toward a functional
      role for pentraxins in the host defence repertoire of fish.

PMID- 15854683
TI  - Activation of TLR3 and TLR5 in channel catfish exposed to virulent Edwardsiella
      ictaluri.
AB  - Two toll-like receptors (TLR3 and TLR5) were identified from a catfish cDNA fry
      library based on sequence similarity to other vertebrate TLR genes. Expression
      (using real-time PCR) of TLR3 and TLR5 was measured for two strains of channel
      catfish in previously non-exposed fish 2, 5, 8, and 21 days after experimental
      Edwardsiella ictaluri challenge to determine if TLRs are associated with host
      response to E. ictaluri infection. Expression of TLR5 was higher than TLR3
      (P<0.0001). TLR3 expression in kidney was elevated in Norris strain (P=0.480) and
      differed over time in spleen (P=0.0134). Fold induction of TLR5 compared to non
      exposed fish increased on days 5 (Norris; 154.72+/-62.12 fold induction) and 8
      (USDA103; 164.65+/-50.56) post-exposure in liver and was slightly increased on
      day 5 (Norris; 10.17+/-24.73, USDA103; 42.56+/-24.73) in kidney. Upregulation of
      TLR3 suggests a more widespread function in primitive fish. TLR5 was highly
      expressed in liver tissue, which may be due to macrophage aggregation during ESC
      infection. This suggests that toll-like receptors are an important component of
      the innate immune system of catfish.

PMID- 15854684
TI  - Cloning and characterization of Xenopus beta2-microglobulin.
AB  - cDNAs for Xenopus beta2-microglobulin (beta2m), the obligatory light chain of
      most vertebrate Major Histocompatibility Complex (MHC) class I molecules, were
      isolated and ESTs were identified. Alignment of the deduced amino acid sequence
      to other species' beta2m showed that the overall structure is evolutionarily
      conserved, and phylogenetic analysis showed that the Xenopus beta2m sequence is
      intermediate between fish and bird/mammal beta2m. The Xenopus beta2m mRNA is
      expressed ubiquitously with highest expression in intestine, spleen, and thymus,
      correlating well with classical class Ia expression. beta2m mRNA and protein were
      also detected in Xenopus thymic tumor and kidney cell lines. Segregation analysis
      on a tetraploid Xenopus laevis family revealed two independently segregating, non
      MHC-linked loci. As expected, only one locus was found in the diploid Xenopus
      tropicalis, strongly suggesting that the two beta2m loci in the tetraploid
      species were generated by genome-wide duplication, and did not undergo
      diploidization unlike many other MHC genes.

PMID- 15854685
TI  - Characterization of duck leucocytes by monoclonal antibodies.
AB  - cDNAs encoding CD3epsilon, CD4 and the alpha-chain of CD8 of ducks were cloned.
      Monoclonal antibodies against Pekin duck CD4 and CD8alpha revealed that the
      antigens were expressed by the majority of thymocytes and by subpopulations of
      CD3+ cells in peripheral tissues. CD8alpha cell surface expression was also found
      on 90% of bursal cells. The B cell specificity of a newly developed mab to the
      immunoglobulin light-chain (L-chain) was confirmed by double labelling studies
      with the chicken B-cell cytokine BAFF. Using these tools and a mab reacting with
      the cytoplasmic domain of CD3epsilon, we demonstrated that the CD8alpha molecule
      is expressed to high levels in CD3-positive T cells and at lower levels in CD3
      negative bursal and peripheral B cells. Mab 2-4, which recognizes the chicken
      CD28 molecule, was found to react with CD4-positive duck lymphocytes and with CD8
      positive duck T cells but not with CD8-positive B cells. Mab K1, which recognizes
      a common antigen on chicken thrombocytes and monocytes/macrophages, was found to
      react with duck thrombocytes and macrophages. Thus, a range of mabs is now
      available which will allow to phenotype the major leucocyte populations in ducks,
      a surrogate infection model for hepatitis B virus.

PMID- 15854687
TI  - Methods to determine the growth domain in a multidimensional environmental space.
AB  - Data from a database on microbial responses to the food environment (ComBase, see
      www.combase.cc) were used to study the boundary of growth several pathogens
      (Aeromonas hydrophila, Escherichia coli, Listeria monocytogenes, Yersinia
      enterocolitica). Two methods were used to evaluate the growth/no growth
      interface. The first one is an application of the Minimum Convex Polyhedron (MCP)
      introduced by Baranyi et al. [Baranyi, J., Ross, T., McMeekin, T., Roberts, T.A.,
      1996. The effect of parameterisation on the performance of empirical models used
      in Predictive Microbiology. Food Microbiol. 13, 83-91.]. The second method
      applies logistic regression to define the boundary of growth. The combination of
      these two different techniques can be a useful tool to handle the problem of
      extrapolation of predictive models at the growth limits.

PMID- 15854688
TI  - Modelling the variability of lag times and the first generation times of single
      cells of E. coli.
AB  - A mathematical model combining deterministic and stochastic elements describes
      the growth and division of single cells. Its deterministic part is based on the
      model of Baranyi and Roberts [International Journal of Food Microbiology 23
      (1994) 277] modelling the gradual adjustment of the cells to a new environment.
      The stochastic part assumes a random threshold size for the division of a single
      cell, which accounts for the variability of the individual generation times.
      Experimental results of the first division times of thousands of single cells
      using a microscopic flow system could be reproduced with this model, and it has
      the potential to be used to study the effects of different stress and
      environmental factors on the distribution of the lag and generation times of
      individual cells.

PMID- 15854689
TI  - A quasi-chemical model for the growth and death of microorganisms in foods by non
      thermal and high-pressure processing.
AB  - Predictive microbial models generally rely on the growth of bacteria in
      laboratory broth to approximate the microbial growth kinetics expected to take
      place in actual foods under identical environmental conditions. Sigmoidal
      functions such as the Gompertz or logistics equation accurately model the typical
      microbial growth curve from the lag to the stationary phase and provide the
      mathematical basis for estimating parameters such as the maximum growth rate
      (MGR). Stationary phase data can begin to show a decline and make it difficult to
      discern which data to include in the analysis of the growth curve, a factor that
      influences the calculated values of the growth parameters. In contradistinction,
      the quasi-chemical kinetics model provides additional capabilities in microbial
      modelling and fits growth-death kinetics (all four phases of the microbial
      lifecycle continuously) for a general set of microorganisms in a variety of
      actual food substrates. The quasi-chemical model is differential equations (ODEs)
      that derives from a hypothetical four-step chemical mechanism involving an
      antagonistic metabolite (quorum sensing) and successfully fits the kinetics of
      pathogens (Staphylococcus aureus, Escherichia coli and Listeria monocytogenes) in
      various foods (bread, turkey meat, ham and cheese) as functions of different
      hurdles (a(w), pH, temperature and anti-microbial lactate). The calculated value
      of the MGR depends on whether growth-death data or only growth data are used in
      the fitting procedure. The quasi-chemical kinetics model is also exploited for
      use with the novel food processing technology of high-pressure processing. The
      high-pressure inactivation kinetics of E. coli are explored in a model food
      system over the pressure (P) range of 207-345 MPa (30,000-50,000 psi) and the
      temperature (T) range of 30-50 degrees C. In relatively low combinations of P and
      T, the inactivation curves are non-linear and exhibit a shoulder prior to a more
      rapid rate of microbial destruction. In the higher P, T regime, the inactivation
      plots tend to be linear. In all cases, the quasi-chemical model successfully fit
      the linear and curvi-linear inactivation plots for E. coli in model food systems.
      The experimental data and the quasi-chemical mathematical model described herein
      are candidates for inclusion in ComBase, the developing database that combines
      data and models from the USDA Pathogen Modeling Program and the UK Food
      MicroModel.

PMID- 15854690
TI  - Development of a global stochastic model relating the distribution of individual
      cell and population physiological states.
AB  - Our ability to predict the lag (lambda) prior to growth of foodborne pathogens is
      limited by our lack of understanding of the physiological changes taking place in
      the individual cell during the adaptation process. Theoretical models have been
      developed to describe the stochastic nature of individual cells, and probability
      distributions have been used to assign hypothetical values of the physiological
      state to individual cells (p(i)). The aim of this study is to develop a
      polynomial model which will link distributions of p(i) values to the
      physiological state of the population (h(0)), and thus to the lambda. Risk
      analysis software was used to simulate values of p(i) for populations of cells
      drawn from lognormal distributions with parameters alpha and beta, and growth
      curves were simulated using a modified continuous-discrete-continuous (CDC)
      model. Values for h(0) were then obtained for each growth curve by fitting with
      the heterogeneous population model (HPM). Multiple regression analysis was used
      to develop a polynomial function which described the subsequent h(0) value as a
      function of alpha and beta (R(2)=0.9957). Outputs from simulations using the
      polynomial model agree well with results from related stochastic models, and
      suggest that distributions can accurately describe the physiological state of
      cell populations.

PMID- 15854691
TI  - Modelling the individual cell lag phase: effect of temperature and pH on the
      individual cell lag distribution of Listeria monocytogenes.
AB  - The individual-based approach of the lag phase is gaining interest, especially
      for pathogens that initially contaminate food products in low amounts. In this
      paper, the effect of temperature (30, 10, 7, 4 and 2 degrees C) and pH (7.4, 6.1,
      5.5, 5.0, 4.7 and 4.4) on the individual cell lag phase of Listeria monocytogenes
      was examined in a factorial design, using OD measurements. Individual lag phases
      of about 100 individual cells per condition were examined and calculated using a
      linear extrapolation method. Generation times were calculated out of the slope.
      The obtained data were analyzed at three different levels: in a first approach,
      the mean values were calculated for each set of environmental conditions and
      compared to predictions made by the USDA's Pathogen Modeling Program (PMP) for
      analogous growth conditions. The PMP predictions of the generation times were in
      the same order of magnitude as the obtained data, although a persistent
      underestimation could be observed. The observed individual cell lag data differed
      from lag phase predictions by PMP. Possible reasons for this discrepancy are
      discussed. Secondly, histograms of individual lag phase measurements were
      constructed for the different temperature-pH combinations. In this way, the
      influence of both factors on the variability of individual lag phases could be
      estimated. At low stress levels, most individual cells showed a short lag phase
      resulting in a compression of the histograms at the zero-lag level, while, at
      high stress levels, the histograms shifted to longer lag phases with a
      significant increase in variability. Thirdly, 37 different distribution types
      were fitted to the datasets to reveal the distributions that fitted best the
      obtained data. The gamma distribution was preferred at moderate stress levels,
      while the Weibull distribution was chosen for harsher growth conditions.

PMID- 15854692
TI  - Obtaining single cells: analysis and evaluation of an experimental protocol by
      means of a simulation model.
AB  - The research presented in this paper analyses a newly developed experimental
      protocol for isolating single cells by constructing a simulation model of the
      process. The protocol involves sequential 50% dilutions of a cell suspension in a
      microtiter plate, so that eventually, wells are obtained containing exactly one
      cell. The aim of this modelling study is (i) to gain insight in the governing
      mechanisms of the dilution process, (ii) to confirm experimental findings and
      (iii) to enable the prediction of an average outcome for future experiments. The
      model construction process is presented chronologically. The initial basic model
      simulates the experiment as a sequence of binomial processes, using Monte Carlo
      techniques. Statistical analysis of the results shows that aggregational factors
      need to be taken into account in the form of a lognormal distribution. Several
      issues involved in this adaptation are discussed. To fully account for cell
      aggregation in the dilution process, a cell clumping algorithm is built into the
      simulation model. Simulation data from the resulting model show similar
      statistical characteristics as the experimental data and yield reliable
      prediction intervals for the available experimental data. The simulation model is
      a useful tool to support experimental findings and predict the outcome of future
      experiments. Even more importantly, this study emphasises the importance of
      careful statistical analysis in single cell research. The impact of stochastic
      effects is considerably amplified at the low cell concentrations involved and
      needs to be taken into account in any modelling effort.

PMID- 15854693
TI  - Germination and growth from spores: variability and uncertainty in the assessment
      of food borne hazards.
AB  - We have developed a model for the variability of spore lag times and shown that
      variability has an important role in the quantitative assessment of risks
      associated with spore forming bacteria in food. The model includes two sequential
      independent delay times that contribute to the lag time for a single spore. We
      have shown that a population of variable spores also has a variable lag time, and
      we have emphasised the significance of this variability in quantitative
      representations of population dynamics for small populations. We have made a
      Bayesian estimate for the extent of the variability in spore lag times and made a
      comparison with direct microscopic observations of individual spores of
      nonproteolytic Clostridium botulinum. We conclude that Bayesian inference is a
      practical method for quantifying variability and hence a significant element in
      the development of quantitative risk assessments for hazards associated with
      spore forming bacteria.

PMID- 15854694
TI  - Modelling the effect of a temperature shift on the lag phase duration of Listeria
      monocytogenes.
AB  - The aim of this work is to study and model the effect of a temperature shift on
      h(0), the product of the growth rate by the lag phase duration (mulambda). Our
      work is based on the data of Whiting and Bagi [Int. J. Food Microbiol. 73 (2002)
      291], who studied the influence of both the pre-incubation temperature (T(prior))
      and the growth temperature (T(growth)) on lambda values of Listeria
      monocytogenes. We introduce a new model to describe the evolution of the
      parameter h(0) as a function of T(prior) and T(growth), and compare it to Whiting
      and Bagi's published polynomial model that describes the influence of T(prior)
      and T(growth) on lambda independently of mu. For exponential as well as
      stationary phase cells, h(0) increases almost linearly with the magnitude of the
      temperature shift. A simple linear model of h(0) turns out to be more suitable to
      predict lambda values than a polynomial model of lambda.

PMID- 15854695
TI  - Quantifying microbial lag phenomena due to a sudden rise in temperature: a
      systematic macroscopic study.
AB  - The microbial lag phase is a complex and yet not completely understood
      phenomenon. Many studies on the microbial lag phase have been published but few
      report a systematic study; moreover, previous lag studies have involved the
      effect of multiple confounded factors. Here, the effect of sudden temperature
      rises on an exponentially growing Escherichia coli culture is systematically
      investigated. Experiments are performed in a computer-controlled bioreactor where
      E. coli K12 MG1655 is grown under aerobic conditions in Brain Heart Infusion
      (BHI) broth. This experimental set-up is used to characterise the effect of (i)
      the amplitude of the temperature shift, (ii) the pre-shift temperature level and
      (iii) the post-shift temperature level on the occurrence and length of a lag
      phase. Besides temperature, no other environmental changes take place at the
      moment of the temperature shift. To quantify the length of the induced lag phase,
      the experimental data are described with a common growth model. Depending on the
      three factors tested, a lag phase of more or less 1 h is induced or not. This
      lag/no lag behaviour can largely be explained by the existence of a normal
      physiological temperature range but also the amplitude of the temperature rise
      plays a role. It can be concluded that for the microorganism under study the
      lower boundary of the normal range lies approximately between 22.78 and 23.86
      degrees C. It is shown that this boundary is no cut-off point, but rather a
      transition zone. Even more, repeated experiments at this boundary have yielded
      different results (lag or no lag). This observation points out that the mechanism
      triggering this lag phase is not absolute but may be subject to biological
      variability.

PMID- 15854696
TI  - Towards a novel class of predictive microbial growth models.
AB  - Food safety and quality are influenced by the presence (and possible
      proliferation) of pathogenic and spoilage microorganisms during the life cycle of
      the product (i.e., from the raw ingredients at the start of the production
      process until the moment of consumption). In order to simulate and predict
      microbial evolution in foods, mathematical models are developed in the field of
      predictive microbiology. In general, microbial growth is a self-limiting process,
      principally due to either (i) the exhaustion of one of the essential nutrients,
      and/or (ii) the accumulation of toxic products that inhibit growth. Nowadays,
      most mathematical models used in predictive microbiology do not explicitly
      incorporate this basic microbial knowledge. In this paper, a novel class of
      microbial growth models is proposed. In contrast with the currently used logistic
      type models, e.g., the model of Baranyi and Roberts [Baranyi, J., Roberts, T.A.,
      1994. A dynamic approach to predicting bacterial growth in food. International
      Journal of Food Microbiology 23, 277-294], the novel model class explicitly
      incorporates nutrient exhaustion and/or metabolic waste product effects. As such,
      this novel model prototype constitutes an elementary building block to be
      extended in a natural way towards, e.g., microbial interactions in co-cultures
      (mediated by metabolic products) and microbial growth in structured foods
      (influenced by, e.g., local substrate concentrations). While under certain
      conditions the mathematical equivalence with classical logistic type models is
      clear and results in equal fitting capacities and parameter estimation quality
      (see Poschet et al. [Poschet, F., Vereecken, K.M., Geeraerd, A.H., Nicolai, B.M.,
      Van Impe, J.F., 2004. Analysis of a novel class of predictive microbial growth
      models and application to co-culture growth. International Journal of Food
      Microbiology, this issue] for a more elaborated analysis in this respect), the
      biological interpretability and extendability represent the main added value.

PMID- 15854697
TI  - Analysis of a novel class of predictive microbial growth models and application
      to coculture growth.
AB  - In this paper, a novel class of microbial growth models is analysed. In contrast
      with the currently used logistic type models (e.g., the model of Baranyi and
      Roberts [Baranyi, J., Roberts, T.A., 1994. A dynamic approach to predicting
      bacterial growth in food. International Journal of Food Microbiology 23, 277
      294]), the novel model class, presented in Van Impe et al. (Van Impe, J.F.,
      Poschet, F., Geeraerd, A.H., Vereecken, K.M., 2004. Towards a novel class of
      predictive microbial growth models. International Journal of Food Microbiology,
      this issue), explicitly incorporates nutrient exhaustion and/or metabolic waste
      product effects inducing stationary phase behaviour. As such, these novel model
      types can be extended in a natural way towards microbial interactions in
      cocultures and microbial growth in structured foods. Two illustrative case
      studies of the novel model types are thoroughly analysed and compared to the
      widely used model of Baranyi and Roberts. In a first case study, the stationary
      phase is assumed to be solely resulting from toxic product inhibition and is
      described as a function of the pH-evolution. In the second case study, substrate
      exhaustion is the sole cause of the stationary phase. Finally, a more complex
      case study of a so-called P-model is presented, dealing with a coculture
      inhibition of Listeria innocua mediated by lactic acid production of Lactococcus
      lactis.

PMID- 15854698
TI  - A model of the specific growth rate inhibition by weak acids in yeasts based on
      energy requirements.
AB  - Zygosaccharomyces bailii, a spoilage yeast, capable of metabolic activity in food
      environments with low pH, low a(w) and in the presence of weak acid preservatives
      was chosen for a study on the effect of benzoic acid on growth parameters. In
      batch cultures, under controlled pH, this food preservative inhibited growth,
      decreasing the specific growth rate (mu) and the yield coefficient (Y(S)) on
      glucose. Data obtained at pH 3.5, 4.0 and 4.5 showed that this inhibition was
      exclusively promoted by the undissociated form of the acid since the effect was
      independent of pH when the concentration of the acid was expressed in this form.
      Moreover, the relationship between the values for mu and Y(S), provided evidence
      that the specific consumption rate of glucose (q(S)) was not affected by benzoic
      acid, indicating that the inhibition of growth should be completely explained by
      a decrease of Y(S). The outcome of parallel experiments performed in continuous
      culture was that the decrease of Y(S) was due to an increase of the maintenance
      coefficient (m), defined as the fraction of q(S) diverted from growth to cope
      with stress, represented in this case by the presence of the preservative. Based
      on these results a model was built, assuming that m increased hyperbolically with
      the concentration of benzoic acid, from zero in the absence of the acid up to
      q(S) when growth was completely inhibited. The concentration of the acid, for
      which m=q(S)/2, is a constant (K(W)), and represents a measure of the tolerance
      for a preservative, in this case benzoic acid. The simple equation
      mu/mu(0)=1+W/K(W) predicts the value of mu for a concentration (W) of the
      preservative, requiring the knowledge of two parameters: the specific growth rate
      in the absence of the preservative (mu(0)) and K(W). The equation fitted very
      well the data of the effect of benzoic acid on the specific growth rate of Z.
      bailii, having K(W)=0.96 mM benzoic acid. The model was also validated with other
      spoilage yeasts grown in the presence of benzoic acid in microtiter plates in an
      automated spectrophotometer. The values obtained for K(W) under these conditions
      confirm Z. bailii as the most tolerant (K(W)=2.1 mM) followed by Pichia sp.
      (K(W)=0.78 mM), Saccharomyces cerevisiae (K(W)=0.53 mM) and Debaryomyces hansenii
      (K(W)=0.11 mM).

PMID- 15854699
TI  - Modelling the growth dynamics of interacting mixed cultures: a case of
      amensalism.
AB  - In this work, a specific membrane bioreactor was used to perform co-cultures of
      two Saccharomyces cerevisiae yeast strains: a killer strain and a sensitive
      strain. Biomass could be segregated into four groups: viable killer yeasts, dead
      killer yeasts, viable sensitive yeasts and dead sensitive yeasts. An existing
      mathematical model describing the population dynamics in the mixed
      killer/sensitive cultures was confronted with the new experimental data. As it
      gave poor accuracy, some improvements were proposed and tested. In particular, a
      lag phase before the beginning of the lethal interaction between the two strains
      was introduced, in correspondence to the experimental observations.

PMID- 15854700
TI  - Simulation of the effect of sausage ingredients and technology on the
      functionality of the bacteriocin-producing Lactobacillus sakei CTC 494 strain.
AB  - Bacteriocin-producing lactic acid bacteria may be applied as novel functional
      starter cultures for sausage fermentation. In this way, safer and more
      standardised end products may be obtained. However, it is not clear how such
      strains behave under sausage fermentation conditions. In this study, the combined
      effects of typical sausage ingredients and process technology on the
      functionality of Lactobacillus sakei CTC 494 were simulated by a modelling
      approach. Under simulated sausage fermentation conditions, the strain was able to
      produce a considerable amount of bacteriocin. Model simulations indicate that
      sausage fermentation conditions of temperature and pH favour bacteriocin
      production, whereas salting and curing with sodium nitrite decrease growth and
      bacteriocin production. Sodium nitrite inhibits cell growth under its
      undissociated nitrous acid form, and its inhibitory effect seems to parallel
      lactic acid production. Whereas oxygen and magnesium levels did not influence
      bacterial functionality, manganese limitations severely decreased cell growth.
      Moreover, the presence of large amounts of fat, which is typical for a sausage
      environment, leads to an apparent bacteriocin inactivation, probably due to
      adsorption of the bacteriocin molecules from the water phase to the fat
      particles.

PMID- 15854701
TI  - Optimal experiment design for cardinal values estimation: guidelines for data
      collection.
AB  - Optimal experiment design for parameter estimation (OED/PE) is an interesting
      technique for modelling practices when aiming for maximum parameter estimation
      accuracy. Nowadays, experimental designs for secondary modelling within the field
      of predictive microbiology are mostly arbitrary or based on factorial design. The
      latter type of design is common practice in response surface modelling
      approaches. A number of levels of the factor(s) under study are selected and all
      possible treatment combinations are performed. It is however not always clear
      which levels and treatment combinations are most relevant. An answer to this
      question can be obtained from optimal experiment design for-in this particular
      case-parameter estimation. This technique is based on the extremisation of a
      scalar function of the Fisher information matrix. The type of scalar function
      determines the final focus of the optimised design. In this paper, optimal
      experiment designs are computed for the cardinal temperature model with
      inflection point (CTMI) and the cardinal pH model (CPM). A model output
      sensitivity analysis (depicting the sensitivity of the model output to a small
      change in the model parameters) yields a first indication of relevant temperature
      or pH treatments. Performed designs are: D-optimal design aiming for a maximum
      global parameter estimation accuracy (by minimising the determinant of the Fisher
      information matrix), and E-optimal design improving the confidence in the most
      uncertain model parameter (by maximising the smallest eigenvalue of the Fisher
      information matrix). Although lowering the information content of a set of
      experiments, boundary values on the design region need to be imposed during
      optimisation to exclude unworkable experiments and partly account for incorrect
      nominal parameter values. Opposed to the frequently applied equidistant or
      arbitrary treatment placement, optimal design results show that typically four
      informative temperature or pH levels are selected and replicate experiments are
      to be performed at these points. Informative experiments are typically placed at
      points with an extreme model output sensitivity.

PMID- 15854702
TI  - Modelling the influence of single acid and mixture on bacterial growth.
AB  - Depending on environmental factors, the prediction of bacterial growth is made
      difficult by the complexity of foodstuff. Although the influence of temperature,
      pH, and water activity are usually taken into account, models have to be
      completed with the influence of acid mixture. Nine strains of Listeria spp., four
      Salmonella spp., one Staphylococcus aureus, one Escherichia coli, and Listeria
      innocua ATCC 33090 were used for this study to extend model proposed by [Le Marc,
      Y., Huchet, V., Bourgeois, C., Guyonnet, J., Mafart, P., Thuault, D., 2002.
      Modelling the growth kinetics of Listeria as a function of temperature, pH and
      organic acid concentration. International Journal of Food Microbiology 73, 219
      237]. Derived from data of [Houtsma, P.C., Kusters, B.J., De Wit, J.C., Rombouts,
      F.M., Zwietering, M.H., 1994. Modelling growth rates of Listeria innocua as a
      function of lactate concentration. International Journal of Food Microbiology 24,
      113-123] and our own data, the extended model described accurately different
      effects of addition of acid salts in the medium (decrease of water activity and
      pH, variation of undissociated weak acid form, and variation of synergetic effect
      between environmental factors). This previous model was implemented to describe
      the observed variability of behaviour of the different studied strains. alpha
      reflected the general behaviour of species (sensitiveness to low or high
      undissociated acid concentration), and MIC(U) reflected the various resistances
      of strains. From this simple model, a new model was built for describing the
      effects of concentrations of several mixed acids on bacterial growth rates.
      Simulations of growth were carried out from three acids mixtures by inputting
      parameter estimates previously obtained. Despite a very variable effect of
      investigated acids on growth, the new model yielded fair predictions.

PMID- 15854703
TI  - Temperature effect on bacterial growth rate: quantitative microbiology approach
      including cardinal values and variability estimates to perform growth simulations
      on/in food.
AB  - Temperature effect on growth rates of Listeria monocytogenes, Salmonella,
      Escherichia coli, Clostridium perfringens and Bacillus cereus, was studied.
      Growth rates were obtained in laboratory medium by using a binary dilutions
      method in which 15 optical density curves were generated to determine one mu
      value. The temperature was in the range from 2 to 48 degrees C, depending on the
      bacterial species. Data were analysed after a square root transformation. No
      large difference between the strains of a same species was observed, and
      therefore all the strains of a same species were analysed together with the same
      secondary model. The variability of the residual error, including both
      measurements errors and biological strain difference, was homogenous for sub
      optimal temperature values. To represent this variability in bacterial kinetic
      simulation, the 95% confidence interval based on an asymptotic Normal
      distribution, around the growth rate value was determined. With this modelling
      approach, the behaviour of bacterial species on food, irrespective of the strain
      or the laboratory, was described. This growth simulation with confidence limits
      has several applications, such as to facilitate comparisons between a challenge
      test and simulation results, and, to appreciate if the temperature change has or
      has not a significant effect on a bacterial growth profile, with regard to the
      uncontrolled factors. The integration of this piece of work in the Sym'Previus
      software is now in process. Results obtained in five French laboratories will be
      extended by working on new food and new microbial species and improved by further
      work on variability estimation.

PMID- 15854704
TI  - Basis of predictive mycology.
AB  - For over 20 years, predictive microbiology focused on food-pathogenic bacteria.
      Few studies concerned modelling fungal development. On one hand, most of food
      mycologists are not familiar with modelling techniques; on the other hand, people
      involved in modelling are developing tools dedicated to bacteria. Therefore,
      there is a tendency to extend the use of models that were developed for bacteria
      to moulds. However, some mould specificities should be taken into account. The
      use of specific models for predicting germination and growth of fungi was
      advocated previously []. This paper provides a short review of fungal modelling
      studies.

PMID- 15854705
TI  - A modified Weibull model for bacterial inactivation.
AB  - In this paper, a modified Weibull model is proposed to fit microbial survival
      curves. This model can incorporate shoulder and/or tailing phenomena if they are
      encountered. We aim to obtain an accurate fit of the "primary" modelling of the
      bacterial inactivation and to provide a useful and meaningful model for
      biologists and food industry. A delta parameter close to the classical concept of
      the D value, established for sterilisation processes, is used in the model. The
      specific parameterisation of the Weibull model is evaluated for the parameter of
      interest delta. The goodness-of-fit of the model is compared to the one produced
      by the model proposed by Geeraerd et al., [Geeraerd, A.H., Herremans, C.H., Van
      Impe, J.F., 2000. Structural model requirements to describe microbial
      inactivation during a mild heat treatment. Int. J. Food Microbiol. 59, 185-209.]
      on experimental data. As our model provides good fits for the different types of
      survival curves analysed, further research can focus on the development of
      suitable secondary model types. In this respect, it is interesting to note that
      the delta parameter is close to the D concept.

PMID- 15854706
TI  - Comparing predicting models for heat inactivation of Listeria monocytogenes and
      Pseudomonas aeruginosa at different pH.
AB  - Under the same experimental conditions it has been demonstrated that whereas
      survival curves of Listeria monocytogenes in the range of temperatures from 54 to
      62 degrees C followed a first-order kinetic, those of Pseudomonas aeruginosa in
      the range of temperatures from 50 to 56 degrees C were not linear showing a
      shoulder followed by a linear region. The first order kinetic model did not
      describe survival curves of P. aeruginosa. A model based on the Weibull
      distribution (Log(10)(N(t)/N(0))=(1/-2.303)*(t/b)(n))) accurately described the
      inactivation kinetics of both microorganisms at the three pHs of 4, 5.5, 7.4
      investigated. For both microorganisms, the b value depended on the treatment
      temperature and the pH of the treatment medium. Whereas for L. monocytogenes the
      n value was independent of the treatment conditions, for P. aeruginosa the n
      value depended on the pH of the treatment medium. The model based on the Weibull
      distribution was capable of accurately predicting the treatment time to
      inactivate five Log(10) cycles of both microorganisms at the three pHs
      investigated.

PMID- 15854707
TI  - Validation of an overall model describing the effect of three environmental
      factors on the apparent D-value of Bacillus cereus spores.
AB  - Several factorial models extending the famous Bigelow model to describe the
      influence of the heating and recovery pH and a(w) conditions on bacterial heat
      resistance have been developed. These models can be associated in an overall
      multifactorial model describing the influences of heating and recovery conditions
      on D values. For Bacillus cereus strain ADQP 407 the model parameters
      characterising the environmental factor influences (pH, Temperature, a(w)) were
      evaluated. Determination of bacterial heat resistance in cream chocolate have
      been realised to validate these parameter values and to evaluate the level of the
      influence of food texture or different compounds not taken account of in the
      model.

PMID- 15854708
TI  - The "Sym'Previus" software, a tool to support decisions to the foodstuff safety.
AB  - Describing the Sym'Previus project, the software and its deliverable facilities
      is the aim of this present paper. This software concerns all the partners of the
      food industry who are involved in the management of food safety and allows food
      borne pathogen behaviour in food to be predicted, as function of the environment
      (nature of the food, manufacturing process, conditions of conservation). This
      analysis of microbial behaviour has been possible thanks to the progress made in
      predictive microbiology since the 1980s. Sym'Previus offers to food industry
      professionals and their partners the possibility of applying this progress, by
      giving access to a database, to simulation systems and expertise.

PMID- 15854709
TI  - Food engineering and predictive microbiology: on the necessity to combine
      biological and physical kinetics.
AB  - Predictive microbiology is mainly applied in the area of risk assessment, but
      unusually regarded as a tool for the optimisation of processes, which needs the
      implementation of food engineering. Combination of predictive microbiology and
      food engineering allows both the assessment of a process in relation to risk and
      its optimisation. Intrinsic comparison between processes in relation to risk, on
      one hand, and the development of process optimisation tools on the other hand,
      necessitates the implementation of new concepts and the involvement of simplified
      and standard calculations based upon reference target strains and environmental
      conditions. Some conventional concepts related to heat treatments are extended,
      while some new ones related to bacterial growth are derived from the gamma
      concept of Marcel Zwietering.

PMID- 15854710
TI  - Development of a Safety Monitoring and Assurance System for chilled food
      products.
AB  - The principles of a novel chill chain management policy, coded Safety Monitoring
      and Assurance System (SMAS) for the optimisation of the distribution of chilled
      food products within the chill chain are developed. In this system, a new
      approach based on actual risk evaluation at important points of the chill chain
      is used in order to promote products to the next stage of distribution. This
      evaluation based on product's time-temperature history, variation in product's
      characteristics (e.g. a(w), pH, etc.), and the use of predictive models for the
      growth of food pathogens, allows to give priority to products in such a way that
      risk at consumption time is minimized. The effectiveness of SMAS was evaluated
      against the First In First Out (FIFO) approach, the current method for food
      distribution, in a case study on the risk of listeriosis of cooked ham using the
      Monte Carlo simulation technique. Furthermore, the two approaches were compared
      for their effect on the quality of the products in terms of remaining shelf life
      at the time of consumption. The results showed that following the SMAS approach
      the risk of listerisosis is significantly lower while the spoiled products at the
      time of consumption are significantly reduced compared to FIFO approach.

PMID- 15854711
TI  - Development of predictive modelling approaches for surface temperature and
      associated microbiological inactivation during hot dry air decontamination.
AB  - This research deals with the development of predictive modelling approaches in
      the field of heat transfer and microbial inactivation. Upon making some backstage
      microbiological considerations, surface temperature predictions during hot dry
      air decontaminations are incorporated in a microbial inactivation model, in order
      to describe inactivation kinetics under realistic (time-varying) temperature
      conditions. In the present study, the following parts are presented. (i) First, a
      one-dimensional heat transfer model is developed taking into account exchanges by
      convection, radiation and evaporation. The model is subsequently validated on a
      laboratory setup and on a test rig, assuming no water activity changes. This test
      rig is developed for studying-at a later stage-surface pasteurisation treatment
      on food products with the use of hot dry air. (ii) Isothermal inactivation data
      of Escherichia coli K12 MG1655 have been collected and inactivation parameters
      are accurately estimated by using a primary and a secondary model in a global
      modelling approach. (iii) Microbiological considerations such as microbial growth
      effects during come-up times, initial temperature of inactivation, and heat
      resistance effects, based on experimental observations and on literature studies,
      are formulated in order to evaluate possible microbial effects arising under the
      dynamic temperature conditions modelled in step (i). (iv) Microbial inactivation
      simulations with the incorporation of surface temperature predictions are
      presented. (v) Finally, the level of the microbial decontamination in an example
      based on the design of an industrial installation is presented, outlining the
      importance of the combination of surface temperature and microbial inactivation
      modelling approaches.

PMID- 15854712
TI  - Accounting for inherent variability of growth in microbial risk assessment.
AB  - Risk assessments of pathogens need to account for the growth of small number of
      cells under varying conditions. In order to determine the possible risks that
      occur when there are small numbers of cells, stochastic models of growth are
      needed that would capture the distribution of the number of cells over replicate
      trials of the same scenario or environmental conditions. This paper provides a
      simple stochastic growth model, accounting only for inherent cell-growth
      variability, assuming constant growth kinetic parameters, for an initial, small,
      numbers of cells assumed to be transforming from a stationary to an exponential
      phase. Two, basic, microbial sets of assumptions are considered: serial, where it
      is assume that cells transform through a lag phase before entering the
      exponential phase of growth; and parallel, where it is assumed that lag and
      exponential phases develop in parallel. The model is based on, first determining
      the distribution of the time when growth commences, and then modelling the
      conditional distribution of the number of cells. For the latter distribution, it
      is found that a Weibull distribution provides a simple approximation to the
      conditional distribution of the relative growth, so that the model developed in
      this paper can be easily implemented in risk assessments using commercial
      software packages.

PMID- 15854713
TI  - Estimating the probability and level of contamination with Salmonella of feed for
      finishing pigs produced in Switzerland--the impact of the production pathway.
AB  - Contaminated feed is a source of infection with Salmonella for livestock,
      including pigs. Because pigs rarely show clinical signs of salmonellosis,
      undetected carriers can enter the food production chain. In a "Farm to Fork" food
      safety concept, safe feed is the first step for ensuring safe food. Heat
      treatment or adding organic acids are process steps for reducing or eliminating a
      contamination with Salmonella. The aims of this study were (I) to estimate the
      probability and the level of Salmonella contamination in batches of feed for
      finishing pigs in Swiss mills and (II) to assess the efficacy of specific process
      steps for reducing the level of contamination with Salmonella. A quantitative
      release assessment was performed by gathering and combining data on the various
      parameters having an influence on the final contamination of feed. Fixed values
      and probability distributions attributed to these parameters were used as input
      values for a Monte Carlo simulation. The simulation showed that-depending on the
      production pathway-the probability that a batch of feed for finishing pigs
      contains Salmonella ranged from 34% (for feed on which no specific
      decontaminating step was applied) to 0% (for feed in which organic acids were
      added and a heat treatment was implemented). If contamination occurred, the level
      of contamination ranged from a few Salmonella kg(-1) feed to a maximum of 8E+04
      Salmonella kg(-1) feed. Probability and levels of contamination were highest when
      no production process able to reduce or eliminate the pathogen was implemented.
      However, most of the Swiss production was shown to undergo some kind of
      decontaminating step. A heat treatment, in combination with the use of organic
      acids, was found as a solution of choice for the control of Salmonella in feed.

PMID- 15854714
TI  - Microbiological risk assessment models for partitioning and mixing during food
      handling.
AB  - To describe the transmission dynamics of a pathogen over a food pathway in
      quantitative microbiological risk assessment (QMRA), several types of processes
      need to be modelled. Next to microbial processes like bacterial growth and
      inactivation, four food handling processes can be identified. Among these are
      partitioning and mixing of the food product. With these processes, the (sizes of)
      units of food product are modified and the pathogenic cells are reallocated over
      the units, so that the prevalence of contaminated units and the number of cells
      per unit may change. Usually, simple models of these processes are applied in
      QMRA food chain models. These models assume independence of units, random
      homogeneous distribution of cells (for partitioning) and equal contribution of
      units (for mixing), which is often not realistic in food and food handling
      processes. In this paper, these assumptions are abandoned. The use of
      multivariate distributions is proposed to include the effect of dependence
      between units: the Multinomial distribution for partitioning and the Dirichlet
      distribution for mixing. Effects of cell clustering and/or unequal sizes of units
      formed by partitioning or contributing to mixing are incorporated. Some
      algorithms are derived that are easily implemented in spreadsheet models that
      simulate food production and preparation. Some examples show the effect of more
      realistic modelling by implementation of these algorithms on the prevalence and
      the probability distribution of the number of pathogens per unit of food product.
      In general, cell clustering will result in lower prevalences, but higher levels
      of contamination in contaminated food units. With the methods presented, these
      effects can be quantified. Difficulties in estimating the model parameters and
      the impact of implementation of the proposed methods on risk estimates in QMRA
      are discussed.

PMID- 15854715
TI  - Individual-based modelling of growth and migration of Salmonella enteritidis in
      hens' eggs.
AB  - An individual-based model (IbM) was developed to describe the growth and
      migration of Salmonella enteritidis in hens' eggs. The Bacteria Simulator
      (BacSim) environment was used to implement the model; the bacteria are
      represented by spheres that grow by nutrient uptake and divide in two daughter
      cells upon exceeding a certain threshold volume. Motility of the Salmonella
      bacteria was described by a run and tumble mechanism. For the sake of simplicity,
      the bacteria were assumed to grow exponentially, an appropriate assumption for
      the initial phase of growth relevant for shelf-life predictions. Both albumen and
      yolk were assumed to be homogeneous. The impact of several model parameters
      (chemotaxis, growth rate, initial contamination numbers and bacterial swimming
      speed) was assessed by a sensitivity analysis. The results show that chemotaxis
      towards the yolk would have a strong effect on the time needed to reach the
      vitelline membrane, an aspect that future research should focus on. The
      contamination position had less impact on the time to reach the vitelline
      membrane. The simulation results illustrate the need for more detailed knowledge
      on the subject of bacterial migration in hens' eggs. Our model can easily
      incorporate this knowledge when it becomes available.

PMID- 15854716
TI  - Models of the behavior of Escherichia coli O157:H7 in raw sterile ground beef
      stored at 5 to 46 degrees C.
AB  - Escherichia coli O157:H7 can contaminate raw ground beef and cause serious human
      foodborne illness. Previous reports describe the behavior of E. coli O157:H7 in
      ground beef under different storage conditions; however, models are lacking for
      the pathogen's behavior in raw ground beef stored over a broad range of
      temperature. Using sterile irradiated raw ground beef, the behavioral kinetics of
      10 individual E. coli O157:H7 strains and/or a 5- or 10-strain cocktail were
      measured at storage temperatures from 5 degrees to 46 degrees C. Growth occurred
      from 6 to 45 degrees C. Although lag phase duration (LPD) decreased from 10.5 to
      45 degrees C, no lag phase was observed at 6, 8, or 10 degrees C. The specific
      growth rate (SGR) increased from 6 to 42 degrees C then declined up to 45 degrees
      C. In contrast to these profiles, the maximum population density (MPD) declined
      with increasing temperature, from approximately 9.7 to 8.2 log cfu/g. Bias (B(f))
      and accuracy (A(f)) factors for an E. coli O157:H7 broth-based aerobic growth
      model (10 to 42 degrees C) applied to the observations in ground beef were 1.05,
      2.70, 1.00 and 1.29, 2.87, 1.03, for SGR, LPD and MPD, respectively. New
      secondary models increased the accuracy of predictions (5 to 45 degrees C), with
      B(f) and A(f) for SGR, LPD, and MPD of 1.00, 1.06, and 1.00 and 1.14, 1.33, and
      1.02, respectively. These new models offer improved tools for designing and
      implementing food safety systems and assessing the impact of E. coli O157:H7
      disease.

PMID- 15854717
TI  - Probabilistic representation of the exposure of consumers to Clostridium
      botulinum neurotoxin in a minimally processed potato product.
AB  - We have examined the potential of a well-specified, minimally processed potato
      product as a vehicle for the exposure of consumers to Clostridium botulinum
      neurotoxin. The product is a relatively simple combination of raw potato flakes,
      flour, starch and other minor ingredients and has an extended lifetime under
      refrigeration conditions. A combination of information and data, from a variety
      of sources that includes the manufacturer, has shown that the product is
      particularly safe with respect to non-proteolytic C. botulinum hazards. The model
      concentrates on a simple end point, the toxicity of an individual retail unit of
      the product at the point of consumer preparation, which is related to an
      individual risk. The probabilistic analysis was built using Bayesian Belief
      Network (BBN) techniques.

PMID- 15854718
TI  - Illuminating reactive microbial transport in saturated porous media:
      demonstration of a visualization method and conceptual transport model.
AB  - We demonstrate a method to study reactive microbial transport in saturated
      translucent porous media using the bacteria Pseudomonas fluorescens 5RL
      genetically engineered to carry a plasmid with bioluminescence genes inducible by
      salicylate. Induced bacteria were injected into a cryolite grain filled chamber
      saturated with a sterile non-growth-promoting (phosphorus limited) chemical
      mixture containing salicylate as an aromatic hydrocarbon analogue. The amount of
      light produced by the bacteria serves as an estimator of the relative efficiency
      of aerobic biodegradation since bioluminescence is dependent on both salicylate
      and oxygen but only consumes oxygen. Bioluminescence was captured with a digital
      camera and analyzed to study the evolving spatial pattern of the bulk oxygen
      consuming reactions. As fluid flow transported the bacteria through the chamber,
      bioluminescence was observed to initially increase until an oxygen depletion zone
      developed behind the advective front. Bacterial transport was modeled with the
      advection dispersion equation and oxygen concentration was modeled assuming
      bacterial consumption via Monod kinetics with consideration of additional effects
      of rate-limited mass transfer from residual gas bubbles. Consistent with previous
      measurements, bioluminescence was considered proportional to oxygen consumed.
      Using the observed bioluminescence, model parameters were fit that were
      consistent with literature values and produced results in good agreement with the
      experimental data. These findings demonstrate potential for using this method to
      investigate the complex spatial and temporal dynamics of reactive microbial
      transport in saturated porous media.

PMID- 15854719
TI  - Prediction of two-phase capillary pressure-saturation relationships in fractional
      wettability systems.
AB  - Capillary pressure/saturation data are often difficult and time consuming to
      measure, particularly for non-water-wetting porous media. Few capillary
      pressure/saturation predictive models, however, have been developed or verified
      for the range of wettability conditions that may be encountered in the natural
      subsurface. This work presents a new two-phase capillary pressure/saturation
      model for application to the prediction of primary drainage and imbibition
      relations in fractional wettability media. This new model is based upon an
      extension of Leverett scaling theory. Analysis of a series of DNAPL/water
      experiments, conducted for a number of water/intermediate and water/organic
      fractional wettability systems, reveals that previous models fail to predict
      observed behavior. The new Leverett-Cassie model, however, is demonstrated to
      provide good representations of these data, as well as those from two earlier
      fractional wettability studies. The Leverett-Cassie model holds promise for field
      application, based upon its foundation in fundamental scaling principles, its
      requirement for relatively few and physically based input parameters, and its
      applicability to a broad range of wetting conditions.

PMID- 15854720
TI  - Effects of skin and hydraulic fractures on SVE wells.
AB  - Soil vapor extraction (SVE) systems are intended to cause substantial volumes of
      air to flow through the subsurface with the purpose of removing volatile
      contaminants. The effectiveness of SVE can be influenced by any effect that
      changes the specific gas capacity (discharge as a function of vacuum) of a well.
      Skins of low permeability material enveloping a well bore are widely recognized
      to affect the performance of wells used to recover water, natural gas, or
      petroleum, and skin can also significantly diminish the performance of an SVE
      well. Skins a few mm thick consisting of material whose gas phase permeability is
      0.01 of the formation can reduce the specific gas capacity of an SVE well by
      factors of 2 to 10 or more. Hydraulic fractures created in the vicinities of
      shallow wells commonly resemble sand-filled layers shaped like flat-lying disks
      or gently dipping saucers. The contrast between the gas-phase permeability of the
      sand in the fracture and that of the formation is particularly important, with
      significant effects requiring the ratio to be greater than approximately 50.
      Shallow hydraulic fractures filled with several tenths of m3 of sand in
      formations that are several orders of magnitude less permeable than that of the
      enveloping formation should increase specific gas capacity by factors of 10 or
      more. Field tests of the effects of hydraulic fractures on the performance of SVE
      were conducted by creating four wells intersecting fractures and a suite of
      control wells created using conventional methods in silty saprolite. Specific gas
      capacities ranged over more than an order of magnitude for 10 wells completed
      within a small area (2 m2) and at the same depth. Specific capacities correlate
      to the drilling method that was used to create the bore for the well: lowest
      values occurred in wells drilled with a machine auger, slightly better results
      were obtained using a Shelby tube, and the best results were obtained from
      conventional wells bored with a hand auger. Skin factors determined for wells
      created with a machine auger could be explained by a layer 1 cm thick that has
      0.007 times the permeability of the enveloping material, which could readily have
      been created during the drilling procedure. Specific capacities of wells
      intersecting hydraulic fractures were 5 to 100 times more than those of
      conventional wells. The large difference in performance appears to be due in part
      to the beneficial effects of the fracture, and in part to the detrimental effects
      of well skin.

PMID- 15854721
TI  - Large-scale effects on resistivity index of porous media.
AB  - The estimation of humidity in the unsaturated zone of soils and NAPL saturation
      in contaminated aquifers may be based on the interpretation of electrical
      resistivity index logs. In the present work, concepts of the theory of the two
      phase flow in pore networks are employed to interpret the form of the equilibrium
      and dynamic resistivity index curves of large porous samples. A resistivity cell
      is constructed to measure the capillary and electrical properties of large
      samples of unconsolidated porous media. The drainage capillary pressure and
      resistivity index curves of a sand column are measured by using the micropore
      membrane (porous plate) method, where a 0.5% wt/vol NaCl aqueous solution is
      displaced by n-dodecane. The dynamic resistivity index curves are measured by
      using the continuous injection technique for various orientations of the sand
      column. Based on concepts of the two-phase flow theory, concerning the dominant
      displacement growth pattern in a pore network and arising from the cooperative
      effects of capillary, buoyancy, and viscous forces, approximate relationships are
      developed for the resistivity index and saturation exponent as functions of the
      water saturation. The saturation exponent decreases as the displacement advances
      and the fluid distribution across the sand column tends to be homogenized after
      oil breakthrough. Both the resistivity index and saturation exponent increase as
      the displacement pattern tends to become compact and stable. In the destabilized
      flow pattern, as the Bond number decreases, the resistivity index may increase
      respectably within a narrow range of values of the Bond number. This happens when
      the thickness of the unstable capillary finger exceeds the lateral dimension of
      the porous sample and becomes a fractal percolation cluster. The saturation
      exponent becomes almost constant and independent of water saturation only over
      the destabilized displacement pattern at high values of the Bond number.

PMID- 15854722
TI  - Co-injection of air and steam for the prevention of the downward migration of
      DNAPLs during steam enhanced extraction: an experimental evaluation of optimum
      injection ratio predictions.
AB  - When steam is injected into soil containing a dense volatile non-aqueous phase
      liquid contaminant, the DNAPL vaporized within the heated soil region condenses
      and accumulates ahead of the steam condensation front. If enough DNAPL
      accumulates, gravitational forces can overcome trapping forces allowing the
      liquid contaminant to flow downward. By injecting air with steam, a portion of
      the DNAPL vapor remains suspended in equilibrium with the air, decreasing liquid
      contaminant accumulation ahead of the steam condensation front, and thus reducing
      the possibility of downward migration. In a previous work, a theoretical model
      was developed to predict the optimum injection ratio of air to steam that would
      eliminate accumulation of DNAPL ahead of the temperature front and thus minimize
      the potential for downward migration. In this work, the theoretical model is
      summarized, and an experiment is presented in order to evaluate the optimum
      injection ratio prediction. In the experiment, a two-dimensional water saturated
      sand pack is contaminated with a known mass of TCE (DNAPL). The system is then
      remediated by co-injecting air and steam at the predicted optimum injection
      ratio, calculated based on the average contaminant soil concentration in the sand
      pack. Results for the co-injection of air and steam are compared to results for
      the injection of pure steam or pure air. Injection at the predicted optimum
      injection ratio for a volumetric average NAPL saturation, reduced accumulation of
      the contaminant ahead of the condensation front by over 90%, as compared to steam
      injection alone. This indicates that the optimum injection ratio prediction is a
      valuable tool for limiting the spreading of DNAPL during steam-enhanced
      extraction. Injection at the optimum injection ratio resulted in earlier recovery
      of contaminant than for steam injection alone. Co-injection of steam and air is
      also shown to result in much higher recovery rates than air injection alone.

PMID- 15854724
TI  - Estimation of biogenic emissions with satellite-derived land use and land cover
      data for air quality modeling of Houston-Galveston ozone nonattainment area.
AB  - The Houston-Galveston Area (HGA) is one of the most severe ozone non-attainment
      regions in the US. To study the effectiveness of controlling anthropogenic
      emissions to mitigate regional ozone nonattainment problems, it is necessary to
      utilize adequate datasets describing the environmental conditions that influence
      the photochemical reactivity of the ambient atmosphere. Compared to the
      anthropogenic emissions from point and mobile sources, there are large
      uncertainties in the locations and amounts of biogenic emissions. For regional
      air quality modeling applications, biogenic emissions are not directly measured
      but are usually estimated with meteorological data such as photo-synthetically
      active solar radiation, surface temperature, land type, and vegetation database.
      In this paper, we characterize these meteorological input parameters and two
      different land use land cover datasets available for HGA: the conventional
      biogenic vegetation/land use data and satellite-derived high-resolution land
      cover data. We describe the procedures used for the estimation of biogenic
      emissions with the satellite derived land cover data and leaf mass density
      information. Air quality model simulations were performed using both the original
      and the new biogenic emissions estimates. The results showed that there were
      considerable uncertainties in biogenic emissions inputs. Subsequently, ozone
      predictions were affected up to 10 ppb, but the magnitudes and locations of peak
      ozone varied each day depending on the upwind or downwind positions of the
      biogenic emission sources relative to the anthropogenic NOx and VOC sources.
      Although the assessment had limitations such as heterogeneity in the spatial
      resolutions, the study highlighted the significance of biogenic emissions
      uncertainty on air quality predictions. However, the study did not allow
      extrapolation of the directional changes in air quality corresponding to the
      changes in LULC because the two datasets were based on vastly different LULC
      category definitions and uncertainties in the vegetation distributions.

PMID- 15854725
TI  - Sensitivity analysis of ground-level ozone concentration to emission changes in
      two urban regions of southeast Texas.
AB  - Air pollutant emission is one of the predominant factors affecting urban air
      quality such as ground-level ozone formation. This paper assesses the impact of
      changing emission inventory scenarios, based on combinations of point, mobile,
      area/non-road and biogenic sources, on the tropospheric ozone concentration in
      two southeast Texas urban areas, i.e. Houston-Galveston and Beaumont-Port Arthur,
      during the rapid ozone formation event (ROFE) on August 25, 2000. The EPA's
      Community Multiscale Air Quality (CMAQ) modeling system with 1999 national
      emission inventory (NEI99) estimates and updated SAPRC99 chemical mechanism are
      used in the sensitivity analysis for twelve different emission scenarios. Based
      on model results, it is found that the point source emission of NOx and VOC
      contributes the greatest ozone peak in the ROFE. Removing Texas point sources of
      VOC and NOx emission from the inventory results in a reduction in peak O3
      concentration by 128 and 70 ppbv in Houston urban area, respectively. Similar but
      less drastic impact from point source is also observed in the Beaumont-Port
      Arthur area. The effect on peak ozone concentration due to mobile, area and non
      road sources emissions are less significant compared to that of point source
      emission. Reducing VOC emission appears to be more effective than reducing NOx
      emission in lowering peak O3 concentration in the studied region. Although
      biogenic emission can contribute up to 37 ppbv of peak ozone level over a large
      area, the affected area is away from the urban region of concern, and should not
      be the main cause for O3 non-attainment in the two urban areas. Removing CO
      emission from mobile sources does not lead to significant reduction (< 1 ppbv) in
      ozone concentrations. The modeled data also show that the transport of O3
      precursors from adjacent states can cause a significant ozone plume near Beaumont
      due to its proximity to the state border based on the conditions during the
      August 25, 2000 O3 episode.

PMID- 15854726
TI  - Regional scale flood modeling using NEXRAD rainfall, GIS, and HEC-HMS/RAS: a case
      study for the San Antonio River Basin Summer 2002 storm event.
AB  - This paper develops a framework for regional scale flood modeling that integrates
      NEXRAD Level III rainfall, GIS, and a hydrological model (HEC-HMS/RAS). The San
      Antonio River Basin (about 4000 square miles, 10,000 km2) in Central Texas, USA,
      is the domain of the study because it is a region subject to frequent occurrences
      of severe flash flooding. A major flood in the summer of 2002 is chosen as a case
      to examine the modeling framework. The model consists of a rainfall-runoff model
      (HEC-HMS) that converts precipitation excess to overland flow and channel runoff,
      as well as a hydraulic model (HEC-RAS) that models unsteady state flow through
      the river channel network based on the HEC-HMS-derived hydrographs. HEC-HMS is
      run on a 4 x 4 km grid in the domain, a resolution consistent with the resolution
      of NEXRAD rainfall taken from the local river authority. Watershed parameters are
      calibrated manually to produce a good simulation of discharge at 12 subbasins.
      With the calibrated discharge, HEC-RAS is capable of producing floodplain
      polygons that are comparable to the satellite imagery. The modeling framework
      presented in this study incorporates a portion of the recently developed GIS tool
      named Map to Map that has been created on a local scale and extends it to a
      regional scale. The results of this research will benefit future modeling efforts
      by providing a tool for hydrological forecasts of flooding on a regional scale.
      While designed for the San Antonio River Basin, this regional scale model may be
      used as a prototype for model applications in other areas of the country.

PMID- 15854727
TI  - Sustainable pattern analysis of a publicly owned Material Recovery Facility in a
      fast-growing urban setting under uncertainty.
AB  - Sustainable development goals are achievable through the installation of Material
      Recovery Facilities (MRFs) in certain solid waste management systems, especially
      those in rapidly expanding multi-district urban areas. MRFs are a cost-effective
      alternative when curbside recycling does not demonstrate long-term success.
      Previous capacity planning uses mixed integer programming optimization for the
      urban center of the city of San Antonio, Texas to establish that a publicly owned
      material recovery facility is preferable to a privatized facility. As a companion
      study, this analysis demonstrates that a MRF alleviates economic, political, and
      social pressures facing solid waste management under uncertainty. It explores the
      impact of uncertainty in decision alternatives in an urban environmental system.
      From this unique angle, waste generation, incidence of recyclables in the waste
      stream, routing distances, recycling participation, and other planning components
      are taken as intervals to expand upon previous deterministic integer-programming
      models. The information incorporated into the optimization objectives includes
      economic impacts for recycling income and cost components in waste management.
      The constraint set consists of mass balance, capacity limitation, recycling
      limitation, scale economy, conditionality, and relevant screening restrictions.
      Due to the fragmented data set, a grey integer programming modeling approach
      quantifies the consequences of inexact information as it propagates through the
      final solutions in the optimization process. The grey algorithm screens optimal
      shipping patterns and an ideal MRF location and capacity. Two case settings
      compare MRF selection policies where optimal solutions exemplify the value of
      grey programming in the context of integrated solid waste management.

PMID- 15854728
TI  - Landfill space consumption dynamics in the Lower Rio Grande Valley by grey
      integer programming-based games.
AB  - The Lower Rio Grande Valley (LRGV) region in South Texas emerges as a warehouse
      and transportation center between Central America and the US with positive growth
      impacts due to the North American Free Trade Agreement (NAFTA). In 10 years time,
      a 39.8% population increase has resulted in a 25% boost in solid waste per capita
      disposal rate in the region. A landfill space shortage drives a need for landfill
      operators to understand their optimal management strategies in this highly
      competitive market. Initially, a strategic plan for optimal solid waste pattern
      distribution minimizes net costs for cities. This is accomplished through a grey
      integer programming algorithm that encapsulates all uncertainty present in the
      solid waste system. Secondly, a series of grey integer submodels construct payoff
      matrices for a zero-sum two-person game. The ensuing game theoretic analysis is
      critical for evaluating optimal pricing strategies for tipping fees available to
      the most significant regional landfills (e.g. Browning-Ferris Industries (BFI)
      and City of Edinburg) as they compete over disposal contracts. The BFI landfill
      intrinsically benefits from its competitive pricing policy and central location
      to solid waste generators. The City of Edinburg landfill, on the other hand,
      wishes to secure its lucrative solid waste management revenue. It desires a
      gaming strategy backed by optimality that integrates ambiguity in solid waste
      generation, design capacity boundaries, and unitary shipping costs. Results show
      that a two-tiered analysis via grey integer programming-based games may pave the
      way for 'grey Nash equilibria' pricing tactics that will help the Edinburg
      landfill maintain its waste contracts.

PMID- 15854729
TI  - An Aquifer Storage and Recovery system with reclaimed wastewater to preserve
      native groundwater resources in El Paso, Texas.
AB  - The traditional concept of Aquifer Storage and Recovery (ASR) has been emphasized
      and extensively applied for water resources conservation in arid and semi-arid
      regions using groundwater systems as introduced in Pyne's book titled Groundwater
      Recharge and Wells. This paper extends the ASR concept to an integrated level in
      which either treated or untreated surface water or reclaimed wastewater is stored
      in a suitable aquifer through a system of spreading basins, infiltration
      galleries and recharge wells; and part or all of the stored water is recovered
      through production wells, dual function recharge wells, or by streams receiving
      increased discharge from the surrounding recharged aquifer as needed. In this
      paper, the author uses the El Paso Water Utilities (EPWU) ASR system for
      injection of reclaimed wastewater into the Hueco Bolson aquifer as an example to
      address challenges and resolutions faced during the design and operation of an
      ASR system under a new ASR system definition. This new ASR system concept
      consists of four subsystems: source water, storage space-aquifer, recharge
      facilities and recovery facilities. Even though facing challenges, this system
      has successfully recharged approximately 74.7 million cubic meters (19.7 billion
      gallons) of reclaimed wastewater into the Hueco Bolson aquifer through 10
      recharge wells in the last 18 years. This ASR system has served dual purposes:
      reuse of reclaimed wastewater to preserve native groundwater, and restoration of
      groundwater by artificial recharge of reclaimed wastewater into the Hueco Bolson
      aquifer.

PMID- 15854730
TI  - Simulation of vegetation dynamics and management strategies on south Texas, semi
      arid rangeland.
AB  - In this paper, we describe a model designed to simulate seasonal dynamics of warm
      and cool season grasses and forbs, as well as the dynamics of woody plant
      succession through five seral stages, in each of nine different plant communities
      on the Rob and Bessie Welder Wildlife Refuge. The Welder Wildlife Refuge (WWR) is
      located in the Gulf Coastal Prairies and Marshes ecoregion of Texas. The model
      utilizes and integrates data from a wide array of research projects that have
      occurred in south Texas and WWR. It is designed to investigate the effects of
      alternative livestock grazing programs and brush control practices, with
      particular emphasis on prescribed burning, the preferred treatment for brush on
      the WWR. We evaluated the model by simulating changes in the plant communities
      under historical (1974-2000) temperature, rainfall, livestock grazing rotation,
      and brush control regimes, and comparing simulation results to field data on
      herbaceous biomass and brush canopy cover collected on the WWR over the same
      period. We then used the model to simulate the effects of 13 alternative
      management schemes, under each of four weather regimes, over the next 25 years.
      We found that over the simulation period, years 1974-2000, the model does well in
      simulating the magnitude and seasonality of herbaceous biomass production and
      changes in percent brush canopy cover on the WWR. It also does well in simulating
      the effects of variations in cattle stocking rates, grazing rotation programs,
      and brush control regimes on plant communities, thus providing insight into the
      combined effects of temperature, precipitation, cattle stocking rates, grazing
      rotation programs, and brush control on the overall productivity and state of
      woody plant succession on the WWR. Simulation of alternative management schemes
      suggests that brush canopy removal differs little between summer and winter
      prescribed burn treatments when precipitation remains near the long-term average,
      but during periods of low precipitation canopy removal is greater under winter
      prescribed burning. The model provides a useful tool to assist refuge personnel
      with developing long-term brush management and livestock grazing strategies.

PMID- 15854731
TI  - Saltcedar control and water salvage on the Pecos river, Texas, 1999-2003.
AB  - A large scale ecosystem restoration program was initiated in 1997 on the Pecos
      River in Western Texas. Saltcedar (Tamarix spp.), a non-native invasive tree, had
      created a near monoculture along the banks of the river by replacing most native
      vegetation. Local irrigation districts, private landowners, federal and state
      agencies, and private industry worked together to formulate and implement a
      restoration plan, with a goal of reducing the effects of saltcedar and restoring
      the native ecosystem of the river. An initial management phase utilizing state-of
      the-art aerial application of herbicide began in 1999 and continued through 2003.
      Initial mortality of saltcedar averaged about 85-90%. Monitoring efforts were
      initiated at the onset of the project to include evaluating the effects of
      saltcedar control on salinity of the river water, efficiency of water delivery
      down the river as an irrigation water source, and estimates of water salvage. To
      date, no effect on salinity can be measured and irrigation delivery was suspended
      in 2002-2003 due to drought conditions. Water salvage estimates show a
      significant reduction in system water loss after saltcedar treatment. However, a
      flow increase in the river is not yet evident. Monitoring efforts will continue
      in subsequent years.

PMID- 15854732
TI  - Linking management and livelihood in environmental conservation: case of the
      Korup National Park Cameroon.
AB  - Biodiversity conservation has emerged within the past two decades as one of the
      most important global challenges confronting national planners, world bodies,
      professionals and academics. Governments faced with increasing biodiversity loss
      as a result of human activities have resorted to the creation of protected areas
      as a strategy to both slow down habitat loss and/or degradation and eventually
      mitigate species extension and reduction rates. However, the creation of a
      protected area can have strong implications on the livelihoods of people
      inhabiting the forest and depending on it, especially those caught within its
      borders. The involvement of such inhabitants in the management process of the
      protected area can be profitable. This paper discusses the case of the Korup
      National Park, Cameroon, considered in the late 1980s by some to be a flagship of
      conservation and development efforts, and later on in the late 1990s by others as
      a catastrophic failure as an example of integrated conservation and development.
      As a means of updating the program's management information base, an in-depth
      participatory and socio-ecological survey was conducted by some of the program's
      technical staff. This study aimed at appraising the extent to which the Park's
      human community of 4200 inhabitants continued to relate to its resources and
      depend on them for their livelihood. The aim was to evaluate the potential links
      between the communities' livelihood and the long-term management and survival of
      the Park as the important biodiversity conservation zone it had been found to be.
      Results indicate that the successful management of a Park like Korup may well
      depend on the involvement of the local communities; and that successful
      management through approaches that minimize the potential contributions and
      aspirations of the local people is difficult to achieve.

PMID- 15854733
TI  - An assessment of household willingness to pay for curbside recycling: a
      comparison of payment card and referendum approaches.
AB  - Curbside recycling is a tool that communities use to reduce the need for landfill
      space. This study provides contingent valuation estimates of household
      willingness to pay (WTP) to continue a curbside recycling program in the face of
      budget cuts. Comparisons of two forms of the contingent valuation method (CVM)
      are provided: a single bounded referendum and a payment card. Neither approach
      emerges as unambiguously superior. Response rates were virtually identical. Both
      approaches show that support for curbside recycling is highly sensitive to price.
      Regression results from the payment card provided a more thorough identification
      of socio-demographic variables associated with WTP than the referendum, but the
      explanatory power of the two regressions did not differ significantly. The
      referendum estimates of mean WTP exceed those from the payment card, although the
      disparities are less than those typically reported in the CVM literature. Local
      policy makers cited the CVM results as influencing their decisions regarding
      funding options for the future of the program, and seemed to appreciate the fact
      that the two approaches provided a fairly narrow range of estimates of WTP. In an
      era when more of the burden of financing of environmental programs is being
      shifted to the local level, use of CVM to estimate the WTP of consumers for
      highly disaggregated goods and services designed to achieve environmental
      improvement will likely become more relevant to local decision makers who are
      interested in understanding their constituents' views.

PMID- 15854734
TI  - Solutions for characterising natural landscapes in New Zealand using geographical
      information systems.
AB  - This paper explores solutions for characterising naturalness in relation to
      visual landscapes using Geographical Information System (GIS). It is argued that
      planners need to identify natural landscapes and monitor changes in their extent.
      Just like the indices that have been developed to describe the state of the
      economy, indices need to be developed that monitor the state of natural
      landscapes. The complications in characterising natural landscapes are outlined
      but it is argued that there is a need to develop definitions of natural
      landscapes that can be operationalised with a GIS. This will have the advantages
      of the efficiency of the technology and that the definition will be explicit and
      the implementation will be independent of the operator. Several GIS solutions are
      provided and these are an analysis of landcover, a density analysis of roads and
      utilities, and an analysis of property sizes. The analysis of property sizes is
      sensitive to many human modifications of the landscape because many developments
      begin with the subdivision of properties. However, it is argued in this paper
      that no one definition will suffice and that all three methods provide different,
      yet important, insights into natural landscape character. An aggregate
      classification of naturalness based on the majority value of the indices is
      demonstrated as well as a range of techniques for expressing the uncertainty of
      the aggregate classification.

PMID- 15854735
TI  - Forecasting land use change and its environmental impact at a watershed scale.
AB  - Urban expansion is a major driving force altering local and regional hydrology
      and increasing non-point source (NPS) pollution. To explore these environmental
      consequences of urbanization, land use change was forecast, and long-term runoff
      and NPS pollution were assessed in the Muskegon River watershed, located on the
      eastern coast of Lake Michigan. A land use change model, LTM, and a web-based
      environmental impact model, L-THIA, were used in this study. The outcomes
      indicated the watershed would likely be subjected to impacts from urbanization on
      runoff and some types of NPS pollution. Urbanization will slightly or
      considerably increase runoff volume, depending on the development rate, slightly
      increase nutrient losses in runoff, but significantly increase losses of oil and
      grease and certain heavy metals in runoff. The spatial variation of urbanization
      and its impact were also evaluated at the subwatershed scale and showed
      subwatersheds along the coast of the lake and close to cities would have runoff
      and nitrogen impact. The results of this study have significant implications for
      urban planning and decision making in an effort to protect and remediate water
      and habitat quality of Muskegon Lake, which is one of Lake Michigan's Areas of
      Concern (AOC), and the techniques described here can be used in other areas.

PMID- 15854736
TI  - Changing abundance of elephants and willingness to pay for their conservation.
AB  - This paper explores the way in which the stated willingness to pay for the
      conservation of Asian elephants in Sri Lanka varies with hypothetical variations
      in their abundance. To do that, it relies on results from a sample of residents
      of Colombo. The willingness to pay function is found to be unusual. It increases
      at an increasing rate for hypothetical reductions in the elephant population
      compared to its current level (a level that makes the Asian elephant endangered)
      and also increases at a decreasing rate for increases in this population from its
      current level. Rational explanations are given for this relationship. The
      relationship is, however, at odds with relationships suggested in some of the
      literature for total economic value as a function of the abundance of a wildlife
      species. It is suggested that willingness to pay for conservation of a species
      rationally includes a strategic element and may not always measure the total
      economic value of a species. Nevertheless, willingness to pay is still policy
      relevant in such cases.

PMID- 15854737
TI  - Time series modelling of global mean temperature for managerial decision-making.
AB  - Climate change has important implications for business and economic activity.
      Effective management of climate change impacts will depend on the availability of
      accurate and cost-effective forecasts. This paper uses univariate time series
      techniques to model the properties of a global mean temperature dataset in order
      to develop a parsimonious forecasting model for managerial decision-making over
      the short-term horizon. Although the model is estimated on global temperature
      data, the methodology could also be applied to temperature data at more localised
      levels. The statistical techniques include seasonal and non-seasonal unit root
      testing with and without structural breaks, as well as ARIMA and GARCH modelling.
      A forecasting evaluation shows that the chosen model performs well against rival
      models. The estimation results confirm the findings of a number of previous
      studies, namely that global mean temperatures increased significantly throughout
      the 20th century. The use of GARCH modelling also shows the presence of
      volatility clustering in the temperature data, and a positive association between
      volatility and global mean temperature.

PMID- 15854738
TI  - Phosphate uptake and release rates with different carbon sources in biological
      nutrient removal using a SBR.
AB  - A three-step sequencing batch reactor (SBR) was used for nutrient removal from
      synthetic wastewater with different glucose-organic acid mixtures (1/1). Acetic,
      butyric, propionic and citric acids were used as organic acids along with
      glucose. The operation consisted of anaerobic, anoxic and oxic (An/Ax/Ox) phases
      with durations of 2/1/4.5h. Sludge age was kept constant for 10 days. Phosphate
      release and uptake rates were determined for different glucose-organic acid
      mixtures in the feed wastewater. Maximum phosphate uptake (8.1mgPl(-1)h(-1)) and
      release rates (2.23mgPl(-1)h(-1)) were obtained with the glucose-citric acid
      mixture. The highest (96%) percent phosphate removal at the end of the nutrient
      removal cycle (7.5h) was also obtained with the glucose-citric acid mixture while
      the glucose-acetic acid mixture resulted in comparable percent phosphate removal
      (95%).

PMID- 15854739
TI  - Soil carbon stocks and changes in the Republic of Ireland.
AB  - The soil carbon (C) stock of the Republic of Ireland is estimated to have been
      2048 Mt in 1990 and 2021 Mt in 2000. Peat holds around 53% of the soil C stock,
      but on 17% of the land area. The C density of soils (tCha(-1)) is mapped at 2 km
      x 2 km resolution. The greatest soil C densities occur where deep raised bogs are
      the dominant soil; in these grid squares C density can reach 3000 tCha(-1). Most
      of the loss of soil C between 1990 and 2000-up to 23 MtC (1% of 1990 soil C
      stock)-was through industrial peat extraction. The average annual change in soil
      C stocks from 1990 to 2000 due to land use change was estimated at around 0.02%
      of the 1990 stock. Considering uncertainties in the data used to calculate soil C
      stocks and changes, the small average annual 'loss' could be regarded as 'no
      change'.

PMID- 15854740
TI  - Activation of Src tyrosine kinase in microglia in the rat hippocampus following
      transient forebrain ischemia.
AB  - To better understand the pathophysiological role of Src protein, a non-receptor
      protein tyrosine kinase of 60kDa, in the ischemic brain, we investigated the time
      course and regional distribution of active Src expression by using a specific
      antibody against Tyr416 phosphorylated Src (phospho-Src) in the rat hippocampus
      after transient forebrain ischemia. In the hippocampus of the control animals,
      active Src expression was too low to be detected by immunolabeling. Beginning 4h
      after reperfusion, active Src expression became evident and, after 1 day, had
      increased preferentially in the CA field of the hippocampus proper and the
      dentate gyrus. By day 3, active Src expression markedly increased in the
      pyramidal cell layer of CA1 and the dentate hilar region in temporal correlation
      with neuronal cell death occurring in these areas, where cells typical of
      phagocytic microglia showed phospho-Src immunoreactivity. Double-labeling
      experiments revealed that cells expressing active Src were microglia that stained
      for biotinylated lectin derived from Griffonia simplicifolia (GSI-B4). Active Src
      expression began to decline at day 7 and returned to the basal level by day 14
      after reperfusion. These results demonstrate increased phosphorylation of Src in
      activated microglia of the post-ischemic hippocampus, indicating that Src
      signaling may be involved in the microglial reaction to an ischemic insult.

PMID- 15854741
TI  - Angiotensin-converting enzyme (ACE) interacts with dopaminergic mechanisms in the
      brain to modulate prepulse inhibition in mice.
AB  - A renin-angiotensin system, separate to that in the periphery, has been found in
      the brain. Angiotensin-converting enzyme (ACE) is crucial in the synthesis of
      angiotensin II, breakdown of bradykinin and the hydrolysis of several other
      neuropeptides such as enkephalin, substance P, dynorphin and neurotensin. Changes
      in the levels of ACE have been found in brains of schizophrenia patients,
      suggesting an involvement of ACE in the illness which awaits further
      investigation. Prepulse inhibition (PPI) has been suggested to be an operational
      measure of sensorimotor gating and is disrupted in patients with schizophrenia.
      We found that ACE knockout mice have increased startle responses but no
      differences in baseline PPI compared to wildtype controls. Treatment with the
      dopamine receptor agonist, apomorphine, or the dopamine-releasing drug,
      amphetamine, produced significant disruption of PPI in control mice but not in
      ACE knockout mice. Pretreatment with the ACE inhibitor, captopril, which itself
      did not affect PPI, caused a reduction in the effect of apomorphine on PPI,
      similar to that seen in the ACE knockout mice. These data suggest an important
      role of ACE substrates in modulating dopaminergic mechanisms involved in PPI.
      Further studies are needed to ascertain if angiotensin or other neuropeptides are
      involved in these interactions and to investigate the neurochemical mechanism
      behind these effects.

PMID- 15854742
TI  - Losartan blocks the excitatory effect of peripheral hypertonic stimulation on
      vasopressinergic neurons in hypothalamic paraventricular nucleus in rats:
      electrophysiological and immunocytochemical evidence.
AB  - The effect of peripheral hypertonic stimulation on the neurons of hypothalamic
      paraventricular nucleus (PVN) was investigated in the present study with both
      electrophysiological and immunocytochemical methods. The discharge frequency of
      the neurons with phasic activity in PVN could be increased by intraperitoneal
      (i.p.) injection of hypertonic saline (HS, 1.5M NaCl) (from 2.8 +/- 0.5 Hz to 5.4
      +/- 0.9 Hz, P<0.001). The Fos expression in PVN could be enhanced (from 21.2 +/-
      12.9 to 217.3 +/- 38.5 Fos-positive neurons, P<0.001) by i.p. HS and the majority
      of AVP-positive neurons expressing Fos (91.7 +/- 3.6%) was in magnocellular
      subdivision of PVN. After intracerebroventricular (i.c.v.) injection of losartan,
      angiotensin II type 1 (AT1) receptor antagonist (5 microg/microl), the excitatory
      effect of peripheral hypertonic stimulation on PVN neurons with phasic activity
      was inhibited significantly, and the number of the neurons co-expressing Fos and
      AVP in PVN decreased significantly (P<0.001) as well. The result demonstrated
      that the vasopressinergic neurons in PVN could be excited by peripheral
      hypertonic stimulation, and this excitation might be mediated by angiotensin II
      fibers projecting from subfornical organ to PVN.

PMID- 15854743
TI  - Changes in the expression of Hes5 and Mash1 mRNA in the adult rat dentate gyrus
      after transient forebrain ischemia.
AB  - Accumulating evidence indicates that neurogenesis in the adult brain occurs in
      restricted brain regions, including the hippocampal dentate gyrus and is promoted
      by ischemia. The mechanism responsible for ischemia-induced neurogenesis in the
      adult brain, however, remains unclear. Notch pathway plays a pivotal role in the
      regulation of the timing for differentiation and determination of the fate of
      neural progenitor cells in the developing nervous system. To elucidate the
      mechanism underlying ischemia-induced neurogenesis, we investigated changes in
      the expression of mRNAs of Hes5, which is a downstream target of Notch, and
      Mash1, a neurogenic basic helix-loop-helix factor, which is negatively regulated
      by Hes5, in the adult hippocampal dentate gyrus after transient forebrain
      ischemia. Transient forebrain ischemia was produced by four-vessel occlusion
      procedure in rats. The levels of Hes5 mRNA decreased on days 1 and 3 after the
      start of reperfusion and the decreased levels of the mRNA returned to the basal
      level by 5 days after ischemia. In contrast, the level of Mash1 mRNA increased on
      day 1 and then returned to the basal level by 3 days after ischemia. These
      results suggest that an inhibition of Notch activity and subsequent expression of
      neurogenic basic helix-loop-helix factors, including Mash1, may, at least in
      part, contribute to ischemia-induced neurogenesis in the adult dentate gyrus.

PMID- 15854744
TI  - Differential effects of bupivacaine and tetracaine on capsaicin-induced currents
      in dorsal root ganglion neurons.
AB  - Capsaicin opens the TRPV1 channel, a cation channel that depolarizes and
      activates nociceptive neurons. Following this initial activation, neurons become
      desensitized to subsequent applications of capsaicin as well as to other noxious
      stimuli, a phenomenon attributed primarily to the entry of Ca2+ ions through the
      open TRPV1 channel. This ability of capsaicin to desensitize nociceptors has led
      to its use as an analgesic in the treatment of a variety of chronic pain states.
      Because treatment with capsaicin is initially quite painful, local anesthetics
      are sometimes used to block axonal conduction in nociceptive neurons and thus
      minimize pain. However, local anesthetics might also block TRPV1 and prevent the
      Ca2+ entry required for capsaicin-induced desensitization. We have studied the
      direct effect of local anesthetics on currents induced by capsaicin (1 microM) in
      acutely isolated rat dorsal root ganglion neurons using the whole cell patch
      clamp technique. At the highest concentration tested (1 mM), bupivacaine only
      moderately inhibited the capsaicin-induced current to 55 +/- 27% of control (mean
      +/- S.D.; n=12, p<0.01). Tetracaine (1 mM), on the other hand, enhanced the
      capsaicin-induced current to 151 +/- 34% of control (mean +/- S.D.; n=7, p<0.01).
      These results show that local anesthetics can be used to prevent the initial pain
      induced by application of capsaicin without abolishing, and perhaps even
      enhancing, its desensitizing actions.

PMID- 15854745
TI  - Melatonin attenuates amyloid beta25-35-induced apoptosis in mouse microglial BV2
      cells.
AB  - Melatonin has been reported to possess strong antioxidant actions, and is able to
      directly scavenge a variety of reactive oxygen species (ROS). The present study
      investigated whether melatonin possesses protective effects against Abeta-induced
      cytotoxicity in microglial cells. Cells treated with Abeta exhibited several
      characteristic features of apoptosis, while cells pre-treated with melatonin
      prior to exposure to Abeta showed a decrease in the occurrence of such apoptotic
      features. Several previous studies have demonstrated the involvement of ROS in
      Abeta-induced neurotoxicity, and ROS generated by Abeta have been reported to
      lead to the activation of nuclear factor-kappa B (NF-kappaB), a transcription
      factor; pre-treatment with melatonin in the present study reduced the level of
      Abeta-induced intracellular ROS generation, inhibited NF-kappaB activation, and
      suppressed the Abeta-induced increase in caspase-3 enzyme activity. In addition,
      it was found that pre-treatment with melatonin inhibits Abeta-induced increase in
      the levels of bax mRNA and that it enhances the level of bcl-2 expression. Based
      on these findings, the authors speculate that melatonin may provide an effective
      means of treatment for Alzheimer's disease through attenuation of Abeta-induced
      apoptosis.

PMID- 15854746
TI  - Localization of the Nav1.8 sodium channel isoform at nodes of Ranvier in normal
      human radicular tooth pulp.
AB  - The activation of voltage-gated sodium channels is necessary for action potential
      propagation and multiple sodium channel isoforms have been identified that show a
      differential distribution throughout the nervous system. An evaluation of sodium
      channel localization in the radicular pulp from normal human extracted third
      molars established the presence of the Na(v)1.8 isoform at nodes of Ranvier in a
      subpopulation of the myelinated axons as demonstrated with immunofluorescence
      confocal microscopy. A caspr antibody was used to identify the paranodal region
      of nodes of Ranvier and quantitative analysis revealed that 16.5% of the nodes
      contained significant Na(v)1.8 immunoreactivity. Since the Na(v)1.6 isoform has
      been described as the predominant sodium channel at essentially all nodes, the
      finding of Na(v)1.8 in a subpopulation of nodes suggests that multiple isoforms
      may coexist at some nodes of Ranvier and also suggests that this isoform may be
      an important nodal sodium channel type in the peripheral sensory nervous system
      of humans.

PMID- 15854747
TI  - Vitamin D receptor variants in 192 patients with schizophrenia and other
      psychiatric diseases.
AB  - Intriguing parallels have been noted previously between the biology of Vitamin D
      and the epidemiology of schizophrenia. We have scanned the Vitamin D receptor
      (VDR) gene by DOVAM-S (Detection of Virtually All Mutations-SSCP), a robotically
      enhanced multiplexed scanning method. In total, 100 patients with schizophrenia
      (86 Caucasians and 14 African-Americans) were scanned. In addition, pilot
      experiments were performed in patients with bipolar disorder (BPD) (24), autism
      (24), attention deficit hyperactivity disorder (ADHD) (24), and alcoholism (20).
      A total of 762 kb of the VDR genomic sequence was scanned. R208N and V339I were
      each found in one African-American patient, while absent in 35 African-American
      controls without schizophrenia (2/14 versus 0/35, P=0.08). Within the power of
      the study (> or =1.6-fold relative risk), the common M1T variant is not
      associated with schizophrenia. In the 92 scanned patients with other psychiatric
      diseases, R173S was found in a single patient with bipolar disorder. In
      conclusion, we describe three novel structural variants of the Vitamin D
      receptor. Further study is required to clarify their role, if any, in psychiatric
      disease.

PMID- 15854748
TI  - Annexin 7-immunoreactive microglia in the hippocampus of control and
      adrenalectomized rats.
AB  - Annexin 7 (ANX7), also termed synexin, is a member of the annexin family of
      calcium-binding proteins. In the present study, we examined the distribution and
      cellular localization of ANX7-immunoreactivity in the rat hippocampus and its
      response to adrenalectomy (ADX). ANX7 was co-localized with OX42 in microglia
      distributed throughout the hippocampus of both control and ADX animals. ANX7
      immunoreactivity was not detected in GFAP-positive astrocytes or in hippocampal
      neurons. At 1-week and 4-weeks following ADX, we observed a population of large,
      ameboid, ANX7-immunopositive microglia ("reactive microglia") which were largely
      confined to the granule cell layer of the dentate gyrus throughout its
      rostrocaudal extent. No reactive microglia were present in the hippocampus of
      sham-ADX or ADX + corticosterone treated animals. In 4-weeks ADX animals but not
      1-week ADX, ANX7-immunostaining was significantly increased in the mossy fiber
      layer of CA3, due to the presence of many small, dark-staining "activated
      microglia". Our results show that ANX7 is abundantly expressed in the rat
      hippocampus by different microglial forms (e.g., ramified, activated and reactive
      microglia), suggesting an important role for this calcium-binding protein in
      microglial Ca2+-dependent processes.

PMID- 15854749
TI  - The administration of cobra venom factor reduces post-ischemic cerebral injury in
      adult and neonatal rats.
AB  - The role of complement in post-ischemic cerebral injury is incompletely
      understood. Therefore, experiments were designed to test the effect of complement
      depletion on cerebral infarct volume in adult rats and cerebral atrophy in
      neonatal rats. Cerebral infarcts were induced in adult rats by transient
      filamentous occlusion of the right middle cerebral artery (MCAO). Cerebral
      atrophy was induced by subjecting 7-day-old rats to ligation of the right common
      carotid artery followed by 2.5h of hypoxia (8% O2). Forty-eight hours after MCAO,
      coronal sections of adult brains were obtained and stained with 2,3,5-triphenyl
      tetrazolium chloride. The infant rat brains were removed for analysis 6 weeks
      after the hypoxic-ischemic insult. Volumes of infarcts and normal hemispheric
      parenchyma were quantified by computer-based planimetry. Twenty-four hours prior
      to MCAO (adults) or hypoxia-ischemia (neonates), each animal received an i.p.
      injection of either 1 mcg/g body weight cobra venom factor (CVF; adult n=11;
      neonatal n=20) or normal saline (adult n=12; neonatal n=24). In the neonates, a
      second dose of CVF or saline was administered 2 days after hypoxia-ischemia. The
      administration of CVF significantly reduced: (1) post-ischemic cerebral infarct
      volume in the adults and (2) post-hypoxic-ischemic cerebral atrophy in the
      neonates. Therefore, complement activation augmented post-ischemic cerebral
      injury in adult and neonatal rats. Complement depletion induced by CVF
      significantly reduced post-ischemic cerebral infarct volume and atrophy in adult
      and neonatal rats.

PMID- 15854750
TI  - The effects of face spatial frequencies on cortical processing revealed by
      magnetoencephalography.
AB  - To study the spatial frequency (SF) effects on cortical face processing, we
      recorded magnetoencephalographic responses in seven healthy subjects to upright
      and inverted human faces. Four face types were used, including original (broad
      band SF, BSF), low SF (LSF, <5 cycles/face), middle SF (MSF, 5-15 cycles/face),
      and high SF (HSF, >15 cycles/face) face images. Using equivalent current dipole
      (ECD) modeling, neuromagnetic M170 responses peaking around 160-185 ms were
      localized in right occipitotemporal region across subjects to BSF faces. M170
      responses to LSF faces showed longer latency and smaller amplitude compared with
      those to BSF faces. We found no significant difference between BSF, MSF, and HSF
      conditions in M170 amplitude or latency. ECD locations for the four upright face
      conditions were close to one another, although the mean locations for MSF or HSF
      seemed more medial than those for BSF or LSF. Longer latencies for inverted than
      upright faces were observed in BSF (183.4+/-8.5 ms versus 168+/-6.9 ms, P<0.001)
      and LSF face conditions (223.6+/-13.1 ms versus 207.3+/-16.3 ms, P<0.01). M170
      ECDs were located more medial for inverted than upright images in either BSF or
      LSF condition. In conclusion, the less M170 activation to LSF faces suggests that
      face parts information is important for early face processing. The cortical
      representations in right occipitotemporal region for configural and face feature
      processing are overlapping. Our findings on the face inversion effect suggest
      that inverted BSF and LSF faces may be processed as objects.

PMID- 15854752
TI  - Rapid in vitro elimination of anesthetic doses of thiopental in the isolated
      guinea pig brain.
AB  - Electrophysiological and metabolic activities in brain tissue preparations
      maintained in vitro may be influenced by the persistent effect of anesthetic
      drugs utilized during tissue dissection. In order to clarify this issue, we
      studied elimination kinetics of the barbiturate thiopental from the brain
      parenchyma in the isolated guinea pig brain maintained in vitro, arterially
      perfused with a protein-free saline solution [M. de Curtis, G. Biella, C.
      Buccellati, G. Folco, Simultaneous investigation of the neuronal and vascular
      compartments in the guinea pig brain isolated in vitro, Brain Res. Protoc. 3
      (1998) 21-28]. At the onset of anesthesia induced by a single i.p. injection of
      125 mg/kg thiopental, the brain concentration of the drug, measured by high
      performance liquid chromatographic assay, was 44.22+/-5.1 mg/L (mean+/-S.E.;
      n=7). After 30 min of arterial perfusion in vitro with a thiopental-free
      solution, the cerebral levels of the barbiturate decreased to 2.03+/-0.56 mg/L
      (n=3), and reached values close to zero within 1 h. No significant changes in
      thiopental elimination curve were observed when in vitro perfusion rate was
      either increased or decreased. The study demonstrates that thiopental is rapidly
      eliminated from the brain tissue with a mono-exponential kinetic. It can be
      concluded that barbiturate anesthesia utilized during brain dissection is not
      likely to influence activities recorded from the in vitro isolated brain
      preparation.

PMID- 15854751
TI  - Visualization of stress-responsive inhibitory circuits in the GAD65-eGFP
      transgenic mice.
AB  - Here, we have revealed that a subset of GABAergic neurons in the mouse brain
      became activated during systemic stress response. Stress-induced expression of
      immediate early gene product c-Fos, as a marker of neuronal activation was
      visualized in a transgenic mouse line expressing enhanced green fluorescent
      protein (eGFP) under the control of the regulatory region of mouse glutamic acid
      decarboxylase (GAD) 65 gene. In most GABAergic regions egfp transgene expression
      corresponded to acknowledged distribution of GABA neurons. Ether inhalation, as a
      strong systemic stressor induced c-Fos expression throughout the stress-related
      circuit, and did not affect the distribution and expression of the eGFP
      transgene. Stress provoked strong neuronal activation in the piriform cortex,
      midline thalamic nuclei, lateral septum (LS), bed nucleus of the stria terminalis
      (BNST), and in parvocellular part of the hypothalamic paraventricular nucleus
      (PVN) as revealed by c-Fos immunfluorescence. Cells in the LS, BNST, and AHA
      including the subparaventricular zone (SPVZ) displayed significant eGFP/c-Fos co
      localization, revealing stress-responsive GABAergic neurons. None of the stress
      activated neurons within the medial parvocellular subdivision of the PVN were
      GABAergic. Our present results suggest that stress-recruited GABAergic neuron
      populations are preferentially located in distinct limbic and hypothalamic
      regions and these neurons might be involved in an inhibitory mechanism that
      counteract the endocrine, autonomic and behavioral aspects of the stress
      response. Furthermore, the present GAD65-eGFP transgenic model seems to be a
      relevant tool to analyze inhibitory control of the central stress circuit at
      single cell level.

PMID- 15854753
TI  - Reduced nNOS expression induced by repeated nicotine treatment in mu-opioid
      receptor knockout mice.
AB  - To determine whether neuronal nitric oxide synthase (nNOS) is involved in
      nicotine-induced behavioral sensitization in mu-opioid receptor knockout mice we
      adopted an immunohistochemical approach. Our results confirm that repeated
      nicotine administration increased locomotor activity in wild-type mice, but
      failed to increase locomotor activity in mu-opioid receptor knockout mice, thus
      suggesting that the mu-opioid receptor is involved in behavioral sensitization.
      Higher numbers of nNOS-positive cells were observed in the striatum of wild-type
      mice repeatedly treated with nicotine than in saline-treated wild-type mice.
      However, mu-opioid receptor knockout mice showed significantly lower nicotine
      induced nNOS expression in the striatum versus wild-type mice. No differences
      were found in the hilus of the dentate gyrus between wild-type and mu-opioid
      receptor knockout mice. These findings demonstrate that the absence of mu-opioid
      receptors can cause a significant reduction in the expression of nNOS in the
      striatum, as induced by repeated nicotine treatment.

PMID- 15854754
TI  - Hemodynamic response to emotional memory recall with eye movement.
AB  - Previous studies on rapid eye movement sleep have demonstrated the effect of eye
      movement on emotional memory. However, the brain mechanism involved in the
      influence of the eye movement on the emotional recall remains unclear. We
      investigated the prefrontal response during an emotional memory recall with and
      without eye movement. Ten healthy volunteers were recruited. The changes in
      concentration of oxygenated hemoglobin ([oxy-Hb]) in the prefrontal cortex were
      examined using near-infrared spectroscopy (NIRS) during a task that involved
      emotional recall with and without eye movement. Six participants demonstrated a
      significant increase in [oxy-Hb] during emotional recall, and the level of
      increase was reduced through repeated emotional recall with eye movement. The
      results suggest that eye movement is associated with a reduction in the
      hemodynamic response to emotional memory recall.

PMID- 15854755
TI  - Transient gamma-band response is dissociated from sensory memory as reflected by
      MMN.
AB  - The auditory gamma-band transient oscillatory response has been considered to
      reflect early cognitive processing and attention triggering, as has been
      suggested of the mismatch negativity (MMN). We examined whether the auditory
      gamma-band response was related to sensory memory as reflected by MMN. During the
      electroencephalogram (EEG) recordings, approximately 2000 click sounds were
      presented to nine healthy adult subjects with constant SOA of 120 or 170 ms in an
      ignored condition. At a probability of 10%, a click sound was randomly omitted
      from the stimulus sequence. EEG epochs responding to omitted clicks and to click
      sounds were averaged for analysis, respectively, and then those were convoluted
      by Gabor wavelet for the gamma-band response calculation. The MMN to a deviant
      omission in a sequence of click sounds was elicited with SOA of 120 ms which was
      shorter than the duration of temporal window of integration, whereas no MMN was
      elicited with SOA of 170 ms. In contrast with the MMN, the transient gamma-band
      response clearly commenced after the stimuli but not after the omissions,
      regardless whether SOA was short or long. The findings indicate that the brain
      process underlying the transient gamma-band response should be dissociated from
      the sensory memory function.

PMID- 15854756
TI  - Differential effects of clozapine on ethanol-induced ascorbic acid release in
      mouse and rat striatum.
AB  - Previous studies have shown that acute systemic administration of ethanol-induced
      striatal ascorbic acid (AA) release in mice and rats. In the present study, in
      vivo brain microdialysis coupled with high performance liquid chromatography
      (HPLC) with electrochemical detection (ECD) was used to comparatively evaluate
      the effects of clozapine on ethanol-induced AA release in mouse and rat striatum.
      The results showed that clozapine, at the dose of 15 mg/kg i.p., had no effect on
      basal AA or ethanol-induced AA release in rat striatum. The potentiating effect
      of clozapine on ethanol-induced striatal AA release was still observed in rats,
      at the higher dose of 30 mg/kg. In contrast, clozapine significantly inhibited
      ethanol-induced AA release in mouse striatum, at the dose of 15 and 30 mg/kg,
      without affecting basal AA release. The present study suggested that clozapine
      differentially regulated ethanol-induced AA release in the mouse and rat
      striatum.

PMID- 15854757
TI  - Speeded right-to-left information transfer: the result of speeded transmission in
      right-hemisphere axons?
AB  - Both reaction time (RT) and evoked potential (EP) studies have shown that
      interhemispheric transfer is faster from the right to the left hemisphere than
      vice versa. This has been explained either in terms of an asymmetry of callosal
      fibres or as a result of hemispheric specialization. Here we suggest that it may
      be due to greater activity resulting from a greater number of fast-conducting,
      myelinated fibres in the right hemisphere than in the left. Interhemispheric
      transfer times (IHTTs) were measured in 13 males by comparing latencies and
      amplitudes of N160 EPs ipsilateral and contralateral to checkerboard stimuli
      presented to the left or right visual field. IHTT estimates were obtained from
      three homologous electrode pairs. The shorter IHTT from right-to-left was
      associated with a concomitant increase in N160 negativity in the right
      hemisphere. There was no evidence from RTs to stimuli in each visual field to
      suggest that the right hemisphere was dominant for this task, suggesting that the
      faster speed of transfer from the right-to-left hemisphere may depend on faster
      axonal conduction in the right hemisphere relative to the left.

PMID- 15854758
TI  - Retrograde dopaminergic neuron degeneration following intrastriatal proteasome
      inhibition.
AB  - Recent studies have suggested that defects in the ubiquitin-proteasome system
      (UPS) contribute to the etiopathogenetic mechanisms underlying dopaminergic
      neuronal degeneration in Parkinson's disease. The present study aims to study the
      effects of proteasome inhibition in the nerve terminals of nigrostriatal
      dopaminergic neurons in the substantia nigra pars compacta (SNpc). Following a
      unilaterally intrastriatal injection of lactacystin, a selective proteasome
      inhibitor, dopaminergic neurons in the ipsilateral SNpc progressively degenerated
      with alpha-synuclein-immunopositive intracytoplasmic inclusions. When lactacystin
      was administered at a high concentration, the striatum was simultaneously
      involved, and alpha-synuclein-immunopositive extracytoplasmic granules appeared
      extensively within the SN pars reticulata (SNpr). In addition, during the
      retrograde neuron degeneration in SN, the level of heme oxygenase-1
      immunopositivity, an oxidative stress marker, was markedly increased in SNpc
      neurons. These results reveal that intrastriatal proteasome inhibition
      sufficiently induces retrograde dopaminergic neuronal degeneration with abundant
      accumulation of alpha-synuclein in the SN.

PMID- 15854759
TI  - Prognostic value of median and tibial somatosensory evoked potentials in acute
      stroke.
AB  - The predictive values of early somatosensory evoked potentials (SSEPs) for the
      functional outcome after stroke are investigated. Ninety-four stroke patients
      (mean age: 61.2, S.D.: 11.8) with CT confirmed diagnoses of middle cerebral
      artery (MCA) infarction in 71 and supratentorial intracerebral hemorrhage in 23.
      Median and tibial SSEPs were recorded within 3 days of onset. SSEP parameters
      were compared to motor (MRC) and functional ability (Barthel index) followed up
      at 1, 3, 6 and 12 months. Upper limb MRC remains the strongest single predictor
      of functional outcome, determining 54.3% of Barthel index value at 12 months. The
      highest predictive value among SSEP parameters has N20-P25 amplitude ratio-34.5%.
      Combined application of upper limb MRC and N20-P25 amplitude ratio provided
      significantly stronger prognostic information-66%. Combined assessment of SSEP
      parameters and muscle power in acute stroke considerably improves prediction of
      functional outcome.

PMID- 15854760
TI  - The regulation of pro-inflammatory gene expression induced by pigment epithelium
      derived factor in rat cultured microglial cells.
AB  - Pigment epithelium-derived factor (PEDF) is a potent and broadly acting
      neurotrophic factor that protects various cultured neurons against apoptotic
      stimuli. To investigate whether PEDF acts not only on neurons, but also glial
      cells, we analyzed the effects of recombinant human PEDF (rhPEDF) on cytokine
      mRNA levels, transcription factors, and signal transduction pathways in cultured
      microglial cells. RT-PCR analysis revealed that pro-inflammatory genes such as IL
      1beta, IL-6, and TNFalpha were induced in rhPEDF-treated cultured microglial
      cells. Furthermore, rapid phosphorylation of CREB protein had occurred in rhPEDF
      treated neonatal astrocytes. Up-regulation of pro-inflammatory genes by rhPEDF
      was blocked by overexpression of dominant negative CREB or a mutated form of
      IkappaBalpha. These results suggest that the induction of pro-inflammatory genes
      by rhPEDF is mediated via activation of NF-kappaB or CREB in microglial cells.
      Taken together, these results demonstrate that PEDF is a multipotent factor,
      capable of affecting not only neurons, but also microglial cells, and suggests
      that it may act as a neuro-immune modulator in the rodent brain.

PMID- 15854761
TI  - The pharmacological stimulation of NMDA receptors via co-agonist site: an fMRI
      study in the rat brain.
AB  - d-Serine has been proposed as an endogenous modulator at the co-agonist glycine
      binding site of N-methyl-d-aspartate (NMDA) receptors. There is still some debate
      as to whether this site is saturated in vivo, but it seems likely that this
      depends on regional differences in local glycine or d-serine concentrations. In
      order to identify areas where the co-agonist site was not fully activated in
      vivo, we studied the effect of intraperitoneal d-serine administration in the rat
      brain using functional magnetic resonance imaging (fMRI). Using contrast agent
      injection, the variations in the relative cerebral blood volume (CBVrel) in
      several regions of interest were evaluated. d-Serine (50 mg/kg) elicited a
      significant statistical increase in the CBVrel in the hippocampus. This effect
      was inhibited by the specific full antagonist of the co-agonist glycine site L
      701,324 indicating that the hippocampal activation occurred through the binding
      of the agonist d-serine to the glycine-binding site of NMDA receptors. This
      result demonstrates that in the hippocampus, the co-agonist sites of NMDA
      receptors are not endogenously saturated under our experimental conditions,
      suggesting an important role of d-serine in the modulation of receptor function
      in the hippocampus.

PMID- 15854762
TI  - The elicitation of phonological and semantic neuromagnetic field components by
      non-words in human auditory sentence comprehension.
AB  - The current research examined whether neuromagnetic field components relating to
      pre-lexical and semantic analysis would be evoked by non-word violations in
      Japanese auditory sentence comprehension. Stimuli contained semantically
      congruent short vowel-duration words, long vowel-duration non-words, and short
      duration non-words with a deviant second syllable. Native speakers listened to
      sentences, while neuromagnetic fields were recorded with a twin 37-channel
      gradiometer system. The results in the 200-400 ms time window showed that at a
      peak latency of approximately 300 ms, vowel-lengthening and deviant-syllable
      violations produced larger magnetic fields than congruent words. In the 450-600
      ms time range, the magnetic fields in response to deviant-syllable violations,
      but not vowel-lengthening violations, were larger than congruent words, with the
      peak latency at approximately 500 ms. The elicitations of M300 and M500
      components in this study support the biphasic hypothesis where a pre-lexical
      phonological analysis stage precedes a post-lexical semantic integration stage in
      lexical recognition of a native language.

PMID- 15854763
TI  - Evolution of brain-derived neurotrophic factor levels after autologous
      hematopietic stem cell transplantation in multiple sclerosis.
AB  - A neuroprotective role of inflammation has been suggested based on that immune
      cells are the main source of brain-derived neurotrophic factor (BDNF). We
      investigated the 3-year evolution of BDNF levels in serum, CSF and culture
      supernatant of peripheral blood mononuclear cells (PBMC), unstimulated and
      stimulated with anti-CD3 and soluble anti-CD28 antibodies, in 14 multiple
      sclerosis patients who underwent an autologous hematopoietic stem cell
      transplantation (AHSCT). BDNF levels were correlated with previously reported MRI
      measures that showed a reduction of T2 lesion load and increased brain atrophy,
      mainly at first year post-transplant. A significant decrease of serum BDNF levels
      was seen at 12 months post-transplant. BDNF values were found significantly lower
      in stimulated but not in unstimulated PBMC supernatants during the follow-up,
      supporting that AHSCT may induce a down-regulation of BDNF production. The only
      significant correlation was found between CSF BDNF levels and T2 lesion load
      before and 1 year after AHSCT, suggesting that BDNF reflects the past and ongoing
      inflammatory activity and demyelination of these highly active patients. Our
      study suggests that AHSCT can reduce BDNF levels to values associated with lower
      activity. This decrease does not seem to correlate with the brain atrophy
      measures observed in the MRI.

PMID- 15854764
TI  - Cognitive correlates of alterations in acetylcholinesterase in Alzheimer's
      disease.
AB  - We recently reported findings of modest loss of cortical acetylcholinesterase
      (AChE) activity in patients with overall mild Alzheimer's disease (AD) using N
      [11C]methyl-pi-peridin-4-yl propionate ([11C]PMP) AChE positron emission
      tomography (PET). To determine cognitive correlates of in vivo cortical AChE
      activity in patients with mild to moderate AD (n=15), and in normal controls (NC,
      n=12) using [11C]PMP AChE PET imaging. Mean cortical AChE activity in the AD
      subjects was mildly reduced (-11.1%) compared to the control subjects (P<0.05).
      Analysis of the cognitive data showed that mean cortical AChE activity was
      significantly associated with performance on a test of attention and working
      memory (WAIS-III Digit Span, R=0.46, P=0.01) but not with tests of delayed short
      or long-term memory functions. Similar findings were present when the analysis
      was limited to the temporal cortex. Cortical AChE activity is more robustly
      associated with functions of attention and working memory compared to performance
      on primary memory tests in AD.

PMID- 15854765
TI  - 'Mature' nerve growth factor is a minor species in most peripheral tissues.
AB  - The classic neurotrophin hypothesis is based on the idea that innervating neurons
      derive 'mature' neurotrophin provided by the target for their survival. Yet large
      precursor forms of the neurotrophin nerve growth factor (NGF) have been reported
      in both central and peripheral tissues. In the present study, immunoblotting was
      used to survey peripheral tissues containing NGF-responsive neurons and to
      characterize various NGF species. These results demonstrate that 'mature' forms
      of NGF, i.e., the 13 and 16kDa species, are rare in sympathetic and sensory
      ganglia and in their peripheral targets, and that large molecular weight NGF
      precursors are abundant. In addition, certain NGF forms predominate in a given
      tissue, with each tissue exhibiting a characteristic NGF expression pattern.
      These findings suggest that NGF processing in peripheral tissues and in NGF
      responsive ganglia may involve a variety of NGF species.

PMID- 15854766
TI  - Processing of conflicting cues in an attention-shift paradigm studied with fMRI.
AB  - We investigated the effects of conflicting cues in visual attention on brain
      function, based on a modified version of the Posner cue-target paradigm. The
      classic paradigm utilizes either a peripheral or centrally placed cue that
      involuntary or voluntary results in a shift of attention to the cued side. The
      modified paradigm involves presenting both a peripheral and central cue at the
      same time, but where the two cues convey conflicting information regarding
      direction of attention. Functional magnetic resonance imaging (fMRI) were used to
      record neuronal activation in localized brain areas and networks when the
      subjects performed the attention task. We hypothesized that the 'exogenous
      invalid/endogenous valid' condition would activate the anterior attention system
      to a larger extent than the 'exogenous valid/endogenous invalid' condition,
      reflecting a need for top-down information processing in this condition. The
      results for performance data showed that the peripheral cue took precedence over
      the centrally placed cue when the two cues were in conflict, since reaction times
      were significantly longer in the "exogenous invalid/endogenous valid" condition.
      The fMRI data showed an increase in activation in the visual cortex, the left
      parietal lobule, and in the left cingulate gyrus in both the exogenous
      valid/endogenous invalid and exogenous invalid/endogenous valid conditions. For
      the exogenous invalid/endogenous valid condition, there were, in addition,
      significant activations also in the inferior and middle frontal gyri, and in the
      precentral gyrus. We interpret these findings as reflecting that these brain
      areas particularly involved in top-down modulation of attention that interferes
      with a bottom-up, exogenous-driven effect.

PMID- 15854767
TI  - Observation of unaveraged giant MEG activity from language areas during speech
      tasks in patients harboring brain lesions very close to essential language areas:
      expression of brain plasticity in language processing networks?
AB  - We describe a series of 12 patients who suffered from lesions adjacent to the
      classic Broca and Wernicke areas and were examined by magnetoencephalography
      (MEG) for presurgical language localization while performing a protocol of
      different language tasks. In these patients very large MEG activity of up to 5pT
      was observed, which was located not only in the adjacent language processing
      brain areas but also in more distant areas, which are part of the language
      processing neuronal network. The high amplitude and the focal spatial extent of
      this activity allowed MEG source localization from the unaveraged data. In nine
      patients sources of this high amplitude activity were even found in the
      homologous language areas on the contralateral, the nondominant side of the
      brain. The physiological interrelationship of these large MEG changes needs to be
      investigated in more detail in further studies especially in the context of
      possible mechanisms for brain plasticity to overcome inhibitory activity of the
      impaired language area.

PMID- 15854768
TI  - c-Fos, N-methyl-d-aspartate receptor 2C, GABA-A-alpha1 immonoreactivity, seizure
      latency and neuronal injury following single or recurrent neonatal seizures in
      hippocampus of Wistar rat.
AB  - To evaluate the long-term effects of single or recurrent prolonged neonatal
      seizures on seizure threshold and neuronal activity in the brain, a novel "twist"
      seizure was induced by coupling early-life flurothyl-induced seizures with later
      exposure to pentylenetetrazol. The authors assigned six neonatal rats for each
      group: the single-seizure group (SS), the recurrent-seizure group (RS) and the
      control group. At postnatal day 46, seizure threshold was examined using
      pentylenetetrazol, and then the brain slices were evaluated with thionine
      staining, in situ end labeling and immunohistochemical studies. The Results
      showed that the rats in SS and RS groups all had reduced latencies to develop
      generalized tonic seizures induced by PTZ compared with controls (P<0.01).
      Morphologic changes, cell loss and apoptotic cells were observed only in those of
      RS group. Significant fos and NR2C-immunoreactive positive cells were seen in
      hippocampus of rats in both SS and RS groups compared with controls (P<0.01). A
      significant decrease in the number of GABA-A-alpha1 immunoreactive positive
      neurons was detected in hippocampus in rats of SS and RS groups compared with the
      controls (P<0.01). We conclude that neonatal rats subjected to prolonged seizures
      have pronounced long-term effects on seizure threshold and neuronal
      neurophysiological activity in the brain. Obvious neuronal injury, however, was
      only seen in rat with recurrent-seizures. Subtle brain damage might occur in rats
      experiencing single prolonged neonatal seizures.

PMID- 15854769
TI  - Maximum Likelihood Integration of rapid flashes and beeps.
AB  - Maximum likelihood models of multisensory integration are theoretically
      attractive because the goals and assumptions of sensory information processing
      are explicitly stated in such optimal models. When subjects perceive stimuli
      categorically, as opposed to on a continuous scale, Maximum Likelihood
      Integration (MLI) can occur before or after categorization-early or late. We
      introduce early MLI and apply it to the audiovisual perception of rapid beeps and
      flashes. We compare it to late MLI and show that early MLI is a better fitting
      and more parsimonious model. We also show that early MLI is better able to
      account for the effects of information reliability, modality appropriateness and
      intermodal attention which affect multisensory perception.

PMID- 15854770
TI  - The nigro-striatal and nigro-amygdaloid pathways undergo different degeneration
      processes in brains of dementia with Lewy bodies.
AB  - We immunohistochemically investigated the degeneration processes of the nigro
      striatal and nigro-amygdaloid pathways and the relationship between the loss of
      dopaminergic neurons and Lewy bodies (LB) formation in the substantia nigra using
      15 autopsied cases of dementia with Lewy bodies (DLB). The number of tyrosine
      hydroxylase (TH)-positive neurons in the substantia nigra and TH-positive axonal
      terminals in the putamen decreased with a specific pattern. The substantia nigra
      possessed alpha-synuclein-positive LB-bearing neurons that were almost evenly
      distributed, while the putamen exhibited diffuse or granular alpha-synuclein
      immunostaining. Most of the granular stains were positive for anti-phosphorylated
      alpha-synuclein antibody, whereas the diffuse stains were negative. These
      findings suggest that the axonal terminals in the putamen undergo abnormal alpha
      synuclein accumulation, but may not always originate from LB-bearing neurons in
      the substantia nigra. The central amygdaloid nucleus contained anti-alpha
      synuclein- and -phosphorylated alpha-synuclein-positive dystrophic axonal
      terminals, the degree of which was greater for cases with granular staining in
      the putamen, and which was proportional to the number of alpha-synuclein-positive
      neurons in the substantia nigra. Thus, the axonal terminals in the central
      amygdaloid nucleus may have originated from LB-bearing neurons in the substantia
      nigra. The results of the present study indicate that the nigro-striatal and
      nigro-amygdaloid pathways undergo different degeneration processes in DLB, and
      suggest that the degeneration of the nigro-amygdaloid pathway more strongly
      reflects LB formation in dopaminergic neurons of the substantia nigra than that
      of the nigro-striatal pathway. In addition, they indicate that there is no direct
      relationship between the loss of dopaminergic neurons and LB formation in the
      substantia nigra.

PMID- 15854771
TI  - Differences in magnetization transfer ratios of the hippocampus between dementia
      with Lewy bodies and Alzheimer's disease.
AB  - We compared magnetization transfer ratios (MTRs) in the brains of patients with
      dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) to determine whether
      regional differences in the brain structures between DLB and AD are detectable
      with magnetization transfer imaging. Seventeen patients with DLB, 31 patients
      with AD and 18 elderly normal controls were included. Although no significant
      differences were found in MTRs in the frontal white matter between the three
      groups, MTRs in the hippocampus, parahippocampus, and posterior cingulate white
      matter in both patients with DLB and AD were significantly lower than those in
      age-matched control subjects. However, MTRs in the hippocampus of patients with
      DLB were significantly higher than those in patients with AD. Logistic regression
      analysis revealed that hippocampal MTR yielded a sensitivity of 76% and a
      specificity of 71% in discriminating DLB from AD. These results may reflect
      underlying histopathological differences with less severe neuronal degeneration
      in the hippocampus of DLB. MTR measurement of the hippocampus may contribute to
      the clinical differentiation between DLB and AD.

PMID- 15854772
TI  - Alpha-synuclein binding to rab3a in multiple system atrophy.
AB  - Glial cytoplasmic inclusions (GCIs) are characteristic protein deposits in
      multiple system atrophy (MSA), which are composed of abnormally phosphorylated,
      partially insoluble alpha-synuclein. In addition, recent studies have shown
      abnormal widespread accumulation of alpha-synuclein in neurons and neuronal
      processes, and in several regions including the thalamus and cerebral cortex in
      MSA. Combined alpha-synuclein and rab3a immunoprecipitation assays have shown
      alpha-synuclein/rab3a binding in the cerebellum and pons (in which GCIs were
      present) and in the cerebral cortex (area 8) (in which GCIs were absent) in MSA
      cases, but not in the cerebellum and cerebral cortex in age-matched controls.
      Similar findings were found in MSA-C and MSA-P cases (olivopontocerebellar
      atrophy and striatonigral degeneration types, respectively), thus indicating
      possible abnormal interactions of alpha-synuclein and rab3a in diseased brains.
      Abnormal alpha-synuclein binding to rab3a was also found in the substantia nigra
      but not in the cerebral cortex in Parkinson's disease. These findings suggest
      membrane and synaptic vesicle trafficking as vulnerable targets in MSA. Since
      rab3a is a member of the Ras super-family of small (21-25 kDa) GTP-binding
      proteins which is involved in the regulation of the internal trafficking,
      exocytosis and neurotransmission, and vesicle endocytosis, the present findings
      might suggest membrane and synaptic vesicle trafficking as vulnerable targets in
      MSA.

PMID- 15854773
TI  - Budesonide epimer R, LAU-8080 and phenyl butyl nitrone synergistically repress
      cyclooxygenase-2 induction in [IL-1beta+Abeta42]-stressed human neural cells.
AB  - Interleukin-1beta (IL-1beta) and amyloid-beta peptide 42 (Abeta42) together
      induce a robust proinflammatory gene expression program in human neural cells in
      primary culture. One consistent genetic marker for this triggered inflammatory
      response is an increase in the expression of cycloooxygenase-2 (COX-2), a
      prostaglandin synthase also found to be up-regulated in neurological disorders
      such as Alzheimer's disease. In this study we provide data illustrating the
      combined effect of three independent classes of compounds: the glucocorticoid
      budesonide epimer R, the platelet-activating factor antagonist LAU-8080, and the
      free radical scavenger phenyl butyl nitrone, upon COX-2 gene activation and
      prostaglandin E2 (PGE2) levels in [IL-1beta+Abeta42]-stressed HN cells. The data
      indicate that specific combinations of repressors of COX-2 activity are
      synergistic in modulating the stress-induced up-regulation of COX-2 and PGE2, and
      this may be of potential therapeutic value in the design of treatment for complex
      neuroinflammatory disorders.

PMID- 15854774
TI  - Cerebral oxygenation declines despite maintained orthostatic tolerance after
      brief exposure to gravitational stress.
AB  - We examined the effect of a single 120 s of exposure to +3Gz (head-to-foot
      inertial forces) centrifugation as orthostatic stress on cerebral oxygenation
      (oxy-Hb) and cerebral blood volume (CBV) changes in response to stand test, in
      order to relate the occurrence of altered cerebral oxygenation control to any
      increase in sympathetic activity. Frontal near-infrared spectroscopy and mean
      arterial blood pressure at brain level (MAPbrain) were recorded in 14 subjects in
      supine and then in standing (10 min) position, before and after +3Gz
      centrifugation. The decrease in oxy-Hb (-7 +/- 5 a.u. versus -27 +/- 4 a.u.,
      P<0.001) and in CBV (-6 +/- 10 a.u. versus -15 +/- 8 a.u., P<0.05) upon standing
      was more important after +3Gz centrifugation, with unchanged MAPbrain (-8 +/- 8
      mmHg versus -3 +/- 11 mmHg). Upon standing, the high-frequency component of heart
      rate was lower (1090 +/- 460 ms2 versus 827 +/- 412 ms2, P<0.05) after +3Gz
      centrifugation. These findings suggest a downward shift in the static cerebral
      autoregulatory curve. We conclude that cerebral vasoconstriction might have
      occurred without centrally mediated increase in the entire peripheral sympathetic
      activity of the body.

PMID- 15854775
TI  - Developmental change of GABAergic postsynaptic current in rat periaqueductal
      gray.
AB  - The present study was designed to examine developmental changes of GABAergic
      spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in periaqueductal
      gray (PAG) neurons mechanically isolated from young (12- to 18-day) and adult (8-
      to 12-week) rats. While the frequency of mIPSCs was similar, the current
      amplitude in adult rats was significantly smaller than in young rats. In the
      study of mIPSC kinetics, all kinetic parameters except for the fast decay time in
      adult rats were smaller or shorter than in the case of young rats. The present
      study demonstrates that a decrease in the amplitude of GABAergic mIPSC during
      development may result from a decrease in the GABA contents of synaptic vesicles
      and from changes in the kinetics of postsynaptic GABA-activated Cl- channels.

PMID- 15854776
TI  - CD14 receptor polymorphism and Alzheimer's disease risk.
AB  - Activation of microglial cells is involved in the inflammatory component of
      Alzheimer's disease (AD), and it may be triggered by infectious pathogens. CD14,
      a receptor upregulated in activated microglia, plays a central role in innate
      immunity through recognition of bacterial lipopolysaccharide and initiation of
      inflammatory response. A polymorphism in the promoter region (-260) of the CD14
      receptor has been found to be related to increased risk of bacterial infections
      and inflammatory diseases such as atherosclerosis. In a case-control study
      utilizing a clinically well-defined group of 310 sporadic AD patients and 310
      control subjects, we investigated whether the CD14 (-260) polymorphism might be
      responsible for susceptibility to AD, and we also examined the combined gene
      effects between CD14 and APOE and several other proinflammatory cytokine genes.
      The current study does not demonstrate an association between CD14 (-260)
      polymorphism and AD, neither through an independent effect nor through
      interaction with APOE epsilon4 allele or interleukin (IL)-1A, IL-6, IL-8, tumor
      necrosis factor (TNF)-alpha, and intercellular adhesion molecule-1 polymorphisms.

PMID- 15854777
TI  - Cell proliferation is reduced in the dentate gyrus of aged but not young Ts65Dn
      mice, a model of Down syndrome.
AB  - Reduced number of neurons is a common feature in Down's syndrome (DS) brains.
      Since reduced neuronal number also occurs in the dentate gyrus of Ts65Dn mice
      (TS), a model for DS, hippocampal cell proliferation and survival were analyzed
      in young and old TS mice. For evaluating proliferation and survival, half of the
      mice were sacrificed 1 day, and the other half 30 days after the last
      bromodeoxyuridine injection, respectively. No difference was found in the number
      of proliferating or surviving cells of young TS and control mice. An age
      associated decline in total cell number and density has been found in both
      genotypes, this decline being more pronounced in TS animals. Thus, aged TS mice
      showed reduced cell proliferation and density of surviving cells compared to CO
      mice. Due to the putative involvement of newborn cells in the dentate gyrus in
      learning processes, the reduced proliferative capacity found in TS mice could be
      involved in the cognitive problems found in this model of Down syndrome.

PMID- 15854778
TI  - Modeling cortisol rhythms in a population-based study.
AB  - The aim of these analyses was to develop and describe easily implementable, yet
      information rich, approaches for analysis of the temporal profile of cortisol in
      human populations. A typical waking profile of cortisol in a sample of women aged
      15-44 was parameterized by a piecewise linear regression model, implemented as a
      mixed model to accommodate repeated observations among individuals. The model was
      extended to distinguish characteristic cortisol profiles of obese women from
      those of non-obese women. Sharp inflection points for the diurnal profile of
      cortisol were noted at 30 and 75 min past awakening. Obese women showed a slight
      tendency to have a less sharply rising and declining response to awakening than
      non-obese women.

PMID- 15854779
TI  - Longitudinal evidence of the impact of normal thyroid stimulating hormone
      variations on cognitive functioning in very old age.
AB  - The purpose of this study was to examine longitudinal associations among thyroid
      stimulating hormone (TSH) levels and cognitive performance. Data collected at the
      first three assessment times, approximately 3 years apart, are reported for the
      survivors (n=45) from a previously published cross-sectional study. Participants
      were aged 75-93 years at baseline, and data reported were collected in the
      Kungsholmen Project, a longitudinal project investigating aging and dementia.
      Analyses revealed that although declining verbal fluency and visuospatial
      abilities were accompanied by simultaneously declining TSH levels, the pattern of
      cross-sectional and longitudinal results are interpreted such that declining TSH
      levels may have caused episodic memory deficits later on. These results were
      obtained in the examination of 6-year but not 3-year change, and after removal of
      the cognitive variation associated with depressive mood symptoms.

PMID- 15854780
TI  - No major month to month variation in free testosterone levels in aging males.
      Minor impact on the biological diagnosis of 'andropause'.
AB  - BACKGROUND: The measurement of bioavailable testosterone (BT) or free
      testosterone (FT) levels is currently considered the gold standard for the
      diagnosis of androgen deficiency in elderly men. While the impact of age on
      circulating testosterone levels (total, bioavailable and free) has been strongly
      documented, the existence of seasonal variations in testosterone levels remains
      debated. OBJECTIVE: We investigated whether seasonal variations in serum
      calculated free testosterone (cFT) levels may translate into variations in the
      prevalence of low testosterone levels. Diagnosis was on the basis of biochemical
      determinations and was cross-checked with the prevalence of clinical signs and
      symptoms of 'andropause', as assessed by the Androgen Deficiency in Aging Males
      (ADAM) questionnaire. METHODS: The study recruited 5028 men aged 50 years and
      over from September 2000 to January 2003. Their serum FT levels were assessed and
      they completed the French ADAM test. Men were considered eugonadal when cFT was >
      or =70 ng/l. The ADAM test was scored as described originally. The prevalence of
      'andropause', diagnosed by the two methods, was compared throughout the year, on
      a month by month basis. RESULTS: The percentage of subjects with cFT levels below
      70 ng/l increased significantly with age (P<0.001). Serum cFT levels (mean [SD])
      varied significantly with the month of sampling (P<0.0001), the highest (88.1
      [30.2] ng/l) and lowest (76.9 [28.0] ng/l) mean values occurring in April and in
      October, respectively. Conversely, the prevalence of testosterone deficiency
      (cFT<70 ng/l) reached a peak in October (45.7%) and a nadir in April (29.7%).
      Although the prevalence of 'andropause', based on the ADAM questionnaire,
      increased significantly with age (P<0.0001), no influence of the month of the
      year was noticed. CONCLUSIONS: Our results confirm a progressive age-related
      decline in FT levels. The monthly variations in serum FT values, observed
      throughout the year, do not show a major seasonal rhythm in elderly community
      dwelling males, since the magnitude of the variations (<15%) remains marginal.
      This slight variation may, however, have an impact on the number of elderly men
      diagnosed with Partial Androgen Deficiency in Aging Males (PADAM).

PMID- 15854781
TI  - Stress and salivary cortisol during pregnancy.
AB  - The purpose of this study was to determine whether exposure to stressful life
      events was associated with changes in levels of circulating cortisol during
      pregnancy in a population of 603 pregnant women. The participating pregnant women
      filled out a questionnaire and collected a morning and evening sample of saliva
      in early pregnancy (median 14th gestational week) and in late pregnancy (median
      and 30th gestational week). They were asked to report the number of life events
      experienced during first and second trimester, respectively, and were asked to
      rate the intensity of the experienced events. Complications related to the
      pregnancy such as vaginal bleeding and suspected growth retardation were
      registered and the women were asked about concerns about their pregnancy. The
      salivary samples were analyzed for cortisol and the levels were higher in late
      than in early pregnancy. In late pregnancy women exposed to more than one life
      event or were concerned about pregnancy complications during second trimester had
      a higher evening cortisol level, whereas morning values were unaffected. After
      adjustment for smoking women who experienced more than one very stressful life
      event had 27% higher evening cortisol concentrations (95% confidence intervals: 1
      59%). Women with worries about pregnancy complications had 27% (95% confidence
      intervals: 2-57%) higher levels. In early pregnancy women reporting stressful
      life events did not have higher evening cortisol levels, but tended to have a
      blunted morning HPA response. In conclusion, we found differences in the
      associations between chronic stress in early and late pregnancy and cortisol
      levels indicating that the response to chronic stress is dependent on the stage
      of the pregnancy.

PMID- 15854782
TI  - Sex steroid-related genes and male-to-female transsexualism.
AB  - Transsexualism is characterised by lifelong discomfort with the assigned sex and
      a strong identification with the opposite sex. The cause of transsexualism is
      unknown, but it has been suggested that an aberration in the early sexual
      differentiation of various brain structures may be involved. Animal experiments
      have revealed that the sexual differentiation of the brain is mainly due to an
      influence of testosterone, acting both via androgen receptors (ARs) and--after
      aromatase-catalyzed conversion to estradiol--via estrogen receptors (ERs). The
      present study examined the possible importance of three polymorphisms and their
      pairwise interactions for the development of male-to-female transsexualism: a CAG
      repeat sequence in the first exon of the AR gene, a tetra nucleotide repeat
      polymorphism in intron 4 of the aromatase gene, and a CA repeat polymorphism in
      intron 5 of the ERbeta gene. Subjects were 29 Caucasian male-to-female
      transsexuals and 229 healthy male controls. Transsexuals differed from controls
      with respect to the mean length of the ERbeta repeat polymorphism, but not with
      respect to the length of the other two studied polymorphisms. However, binary
      logistic regression analysis revealed significant partial effects for all three
      polymorphisms, as well as for the interaction between the AR and aromatase gene
      polymorphisms, on the risk of developing transsexualism. Given the small number
      of transsexuals in the study, the results should be interpreted with the utmost
      caution. Further study of the putative role of these and other sex steroid
      related genes for the development of transsexualism may, however, be worthwhile.

PMID- 15854783
TI  - The effects of stress-induced cortisol responses on approach-avoidance behavior.
AB  - High glucocorticoid stress-responses are associated with prolonged freezing
      reactions and decreased active approach and avoidance behavior in animals. The
      present study was designed to investigate the effects of cortisol responses and
      trait avoidance on approach-avoidance behavior in humans. Twenty individuals were
      administered a computerized approach-avoidance (AA)-task before and after stress
      induction (Trier Social Stress Test). The AA-task involved a reaction time (RT)
      task, in which participants made affect congruent and affect incongruent arm
      movements towards positive and threatening social stimuli. Affect congruent
      responses involved arm extension (avoidance) in response to angry faces and arm
      flexion (approach) in response to happy faces. Reversed responses were made in
      affect incongruent instruction conditions. As expected, participants with high
      cortisol responses showed significantly decreased RT congruency-effects in a
      context of social stress. Low trait avoidance was also associated with diminished
      congruency-effects during stress. However, the latter effect disappeared after
      controlling for the effects of cortisol. In sum, in agreement with animal
      research, these data suggest that high cortisol responses are associated with a
      decrease in active approach-avoidance behavior during stress. These findings may
      have important implications for the study of freezing and avoidance reactions in
      patients with anxiety disorders, such as social phobia and post-traumatic stress
      disorder.

PMID- 15854784
TI  - Relationship between cortisol and age-related memory impairments in Holocaust
      survivors with PTSD.
AB  - RATIONALE: Holocaust survivors with PTSD appear to show an accelerated aging
      effect as evidenced by their performance on tests of explicit memory, and also
      show more exaggerated patterns on age-related alterations in cortisol release
      over the diurnal cycle than Holocaust survivors without PTSD and nonexposed
      subjects. To investigate the implications of age-related HPA axis alterations on
      cognition, we examined correlations between parameters reflecting circadian
      cortisol release and implicit and explicit memory performance. METHODS: Nineteen
      Holocaust survivors with PTSD (7 men, 12 women), 16 Holocaust survivors without
      PTSD (7 men, 9 women), and 28 non-exposed healthy comparison subjects (13 men, 15
      women) collected salivary samples at six times over the diurnal cycle, and were
      tested with Paired Associates and Word Stem Completion Tests. RESULTS: Negative
      correlations were observed between several measures of salivary cortisol
      concentrations and explicit memory in Holocaust survivors with PTSD after
      adjusting for IQ, years of education and current age reflecting poorer
      performance in association with higher cortisol levels. This relationship was
      absent in Holocaust survivors without PTSD and in demographically-comparable
      subjects who were not exposed to the Holocaust or other extremely traumatic
      events. CONCLUSION: The significantly different relationship between cortisol and
      memory performance in these groups suggests that the neuropsychological
      impairments observed in Holocaust survivors with PTSD may reflect an interaction
      of PTSD and aging effects.

PMID- 15854785
TI  - Novel males' capacity to disrupt early pregnancy in mice (Mus musculus) is
      attenuated via a chronic reduction of males' urinary 17beta-estradiol.
AB  - Mature male mice of proven fertility were administered chronic oral doses of
      anastrozole, a potent aromatase inhibitor, and also given a low-phytoestrogen
      diet. Urine was taken non-invasively from such males and from untreated control
      males and assayed for 17beta-estradiol and testosterone via ELISA procedures.
      After 8 weeks of drug or vehicle administration, urinary 17beta-estradiol
      declined to significantly lower levels in anastrozole-treated males than in non
      treated males, whereas testosterone levels were comparable in the two groups.
      Inseminated females were exposed to drug-treated, vehicle-treated, or no males
      during days 1-6 of gestation, around intrauterine implantation of fertilized ova.
      Females exposed to vehicle-treated males produced fewer litters than did those
      kept in isolation. Females exposed to anastrozole-treated males produced
      significantly more litters than did those exposed to vehicle-treated males. These
      data support the notion that male excretions of estrogens may in part mediate
      novel-male-induced pregnancy disruptions, although other influences of
      aromatization on behaviour and metabolism remain possibilities.

PMID- 15854786
TI  - Estimating between- and within-individual variation in cortisol levels using
      multilevel models.
AB  - Cortisol measures often are used to examine variation in hypothalamic-pituitary
      adrenal axis (HPA) activity as well as broader patterns of differential health.
      However, substantial within-individual variation renders single cortisol
      measurements unreliable as estimates for probing differences between individuals
      and groups. A standard practice to clarify between-individual differences
      involves collecting multiple samples from each participant and then deriving
      person-specific averages. By ignoring information about variation at between- and
      within-individual levels, this technique impedes cross-study comparison of
      results, ignores data useful for future study design, and hinders the analysis of
      cross-level interactions. This report describes how multilevel approaches can
      simultaneously model between- and within-individual variation in diurnal cortisol
      levels without using crude averages. We apply these models to data from children
      in Nepal (n=29, 11-15 samples per child), Mongolia (n=47, 8-12 samples per child)
      and the US (n=1269, 1-6 samples per child). Using the Nepal data, we show how an
      analysis of crude time-adjusted aggregates does not detect an association between
      aggressive behavior and cortisol levels, while a multilevel analysis does. More
      importantly, we argue that the 'roadmap' to variation generated by these
      multilevel models provides meaningful information about the predictive accuracy-
      not just statistical significance--of relationships between cortisol levels and
      individual-level variables, such as psychopathology, age, and gender. The
      'roadmap' also facilitates comparison between the results from different studies
      and estimation of the necessary number of cortisol measurements for future
      investigations.

PMID- 15854787
TI  - Gender differences in a fenfluramine-activated FDG PET study of borderline
      personality disorder.
AB  - Neuroimaging studies of impulsive-aggressive subjects with borderline personality
      disorder (BPD) demonstrate hypometabolism in areas of prefrontal and frontal
      cortex, and a blunted cortical metabolic response to challenge with serotonergic
      agonists. Neuroendocrine responses to serotonergic challenge are known to vary
      greatly by gender, and may be related to sex differences in expression of
      impulsive aggression. We conducted single-blind, placebo-controlled fenfluramine
      activated positron emission tomography (PET) studies in impulsive male and female
      subjects with BPD to look for gender differences in cortical response. The sample
      comprised 22 BPD (15 female, 7 male) and 24 control subjects (10 female, 14 male)
      who received placebo on Day 1 and d,l-fenfluramine on Day 2 before PET
      neuroimaging. In response to placebo, female, but not male, controls had areas of
      increased uptake of fluorodeoxyglucose-F18 in prefrontal cortex compared with BPD
      subjects, with greatest uptake in the medial orbital frontal cortex, bilaterally.
      Male, but not female, BPD subjects, showed areas of increased glucose utilization
      compared with controls in large areas of parietal and occipital cortex,
      bilaterally. In response to fenfluramine (relative to placebo), significant
      decreases in glucose uptake were found in male, but not female, BPD subjects,
      centered in the left temporal lobe. Female, but not male, control subjects showed
      significantly decreased uptake in areas of right frontal and temporal cortex.
      Covarying for impulsive-aggression rendered nonsignificant the gender differences
      in responses to placebo or fenfluramine. Gender differences in serotonergic
      function may mediate differences in behavioral expression of impulsive aggression
      in subjects with BPD.

PMID- 15854788
TI  - Abnormal effective connectivity of dopamine D2 receptor binding in schizophrenia.
AB  - Receptor binding has been examined region by region in both in vitro and in vivo
      studies, but less attention has been paid to the connectivity of regional
      receptor binding despite the fact that neurophysiological studies have indicated
      an extensive inter-regional connectivity. In this study, we investigated the
      connectivity of regional dopamine D2 receptor binding in positron emission
      tomography data from 10 drug-naive patients with schizophrenia and 19 healthy
      controls. We applied a structural equation method to regional receptor binding.
      The results indicated that the network models of the patients and normal subjects
      were significantly different. As to the individual path coefficients, (a)
      connectivity between cortical regions was different between groups; (b)
      connectivity from the prefrontal cortex, parietal cortex, and thalamus to the
      anterior cingulate differed from that in controls; and (c) connectivity from the
      prefrontal cortex to the anterior cingulate and thalamus via the hippocampus was
      observed in normal subjects but not in patients. These results suggest that a
      systems-level change reflected in the connectivity of D2 receptor binding is
      present in schizophrenia.

PMID- 15854789
TI  - Volumetric MRI study of the short and long insular cortices in schizophrenia
      spectrum disorders.
AB  - We have previously reported volume reductions of the insular cortex in
      schizophrenia, but it is still not clear whether insular cortex volume loss
      preferentially involves the anterior (short insular cortex) or posterior (long
      insular cortex) portion. On the other hand, no volumetric studies of the brain
      have examined changes in insular cortex volume in subjects with schizotypal
      features. In this study, we separately investigated the volumes of the short and
      long insular cortex portions using magnetic resonance imaging in 37 schizotypal
      disorder patients (24 males, 13 females), 62 schizophrenia patients (32 males, 30
      females), and 69 healthy controls (35 males, 34 females). While the volumes of
      the short and long insular cortex were significantly reduced in schizophrenia
      patients compared with schizotypal disorder patients and control subjects, there
      was no difference between schizotypal disorder patients and control subjects.
      These results suggest that the volume reduction of the insular cortex may be
      specific to overt schizophrenia without topographically specific localization.

PMID- 15854790
TI  - Abnormal development of the anterior cingulate in childhood-onset schizophrenia:
      a preliminary quantitative MRI study.
AB  - The anterior cingulate is a key component of neural networks subserving attention
      and emotion regulation, functions often impaired in patients with psychosis. The
      study aimed to examine anterior cingulate volumes and sulcal morphology in a
      group of patients with childhood-onset schizophrenia (COS) compared with
      controls. Brain magnetic resonance imaging (MRI) scans were obtained in 13 COS
      and 18 matched control children, ages 6-17 years. Volume measures for the
      anterior cingulate gyrus (ACG) were obtained through manual labeling. A
      determination of cingulate sulcal pattern (single or double) was made for each
      hemisphere. The COS group had a reduced leftward skew of the double cingulate
      sulcal pattern, and absence of the normal left>right ACG volume asymmetry. The
      right ACG was larger in the COS than in controls. The schizophrenic children
      showed decreases in all ACG volumes with age, while the controls showed increases
      or no change. The data suggest that significant cingulate abnormalities may
      result from deviations in progressive neurodevelopmental processes, beginning
      before birth and continuing through childhood and adolescence, in persons who
      develop schizophrenia. These structural differences may relate to the well
      described cognitive deficits these children display, and to the cardinal symptoms
      of schizophrenia.

PMID- 15854791
TI  - Behavior and corpus callosum morphology relationships in velocardiofacial
      syndrome (22q11.2 deletion syndrome).
AB  - Velocardiofacial syndrome (VCFS) is a neurodevelopmental disorder caused by a
      microdeletion on chromosome 22q11.2 that predisposes affected individuals to
      learning disabilities and psychiatric conditions. Previous research has indicated
      that compared with comparison children, children with VCFS have larger corpus
      callosal areas. Children with VCFS are often diagnosed with comorbid attention
      deficit hyperactivity disorder (ADHD), and previous research has indicated that
      children with ADHD often have smaller corpus callosal areas than controls. The
      present study investigated two hypotheses: children with VCFS would have larger
      callosal areas than controls, and children with VCFS+ADHD would have smaller
      callosal areas than children with VCFS. Corpus callosum area was obtained from
      the mid-sagittal slice and was assessed in children with VCFS (n=60) and age- and
      gender-matched control participants (n=52). Results indicated that all of the
      corpus callosum measures were significantly different between the two groups
      except for the genu. Across all measures, children with VCFS demonstrated a
      larger corpus callosum area. Within the VCFS sample, children with VCFS+ADHD
      (n=30) had smaller total callosal, splenium, and genu areas than children with
      VCFS alone. Although children with VCFS+ADHD had smaller total callosal areas
      than children with VCFS, relative to control participants, these children had
      larger total callosal and subregion areas except for the genu. In addition to
      other anatomic anomalies, corpus callosal abnormalities appear to be another
      variable to consider when analyzing brain/behavior relations in this population.

PMID- 15854792
TI  - Emotional memory: separating content and context.
AB  - It is now well established that emotion enhances episodic memory. However, it
      remains unclear whether the same neural processes underlie enhancement of memory
      for both emotional stimuli and neutral stimuli encoded in an emotive context. We
      designed an experiment that specifically attempted to separate these effects and
      that was validated on 30 participants. We then used functional magnetic resonance
      imaging (fMRI) to examine the neural correlates of encoding and retrieval of the
      two classes of stimuli in 12 healthy male volunteers. We predicted that aversive
      emotional context would enhance memory regardless of content and that activation
      of anterior cingulate would be inversely related to retrieval of aversive items.
      Both predictions were supported. Furthermore we demonstrated apparent
      asymmetrical lateralisation of activation in the hippocampal/parahippocampal
      complex during recognition of words from aversive sentences: more left-sided
      activation for neutral words from aversive contexts, and more right-sided
      activation for aversive content words. These findings, if applicable to the wider
      population, may have application in a range of psychiatric disorders where
      interactions between emotion and cognition are relevant.

PMID- 15854793
TI  - Correlation between striatal dopamine D2 receptor density and neuroticism in
      community volunteers.
AB  - The central dopaminergic system, as well as the central serotonergic system, has
      been reported to be correlated with higher neuroticism. The present study
      examined the relationship between striatal dopamine D(2) receptor density and
      neuroticism. Neuroticism was assessed with the Maudsley Personality Inventory,
      and psychiatric morbidity was evaluated with both the Mini International
      Neuropsychiatric Interview and the Hamilton Depression Rating Scale (HAM-D).
      Single photon emission computed tomography with [(123)I]iodo-benzamide was used
      to measure striatal dopamine D(2) receptor density. HAM-D scores and psychiatric
      morbidity in high-neuroticism individuals were higher than in low-neuroticism
      individuals. Moreover, striatal dopamine D(2) receptor densities were
      significantly correlated with the neuroticism score of the 41 subjects. The
      central dopaminergic system may play an important role in the neurobiological
      characteristics of neuroticism.

PMID- 15854794
TI  - Failure to find progressive temporal lobe volume decreases 10 years subsequent to
      a first episode of schizophrenia.
AB  - The present study used magnetic resonance imaging to examine the volumes of the
      temporal lobe and the superior temporal gyrus in a 10-year follow-up study of 27
      patients with schizophrenia and 10 controls. No change over time was observed in
      these structures when patients were compared with controls. These results do not
      support the notion that progressive temporal lobe deterioration occurs in
      schizophrenia.

PMID- 15854795
TI  - Gilles de la Tourette syndrome and voluntary movement: a functional MRI study.
AB  - Tourette syndrome (TS) is hypothesised to be caused by an abnormal organization
      of movement control. The aim of this study was to use functional magnetic
      resonance imaging to study motor cortex activation in a TS patient. Usual and
      unusual self-paced voluntary movements were performed. The TS patient displayed
      supplementary motor area (SMA) activation during both tasks. This activation
      reflects a continuous use of the SMA to perform the voluntary motor movements
      required in both tasks. Moreover, the absence of tics during the execution of
      these voluntary motor tasks suggests that tic activity may be suppressed by
      additional mental effort.

PMID- 15854796
TI  - Microdialysis--theoretical background and recent implementation in applied life
      sciences.
AB  - In the past decade microdialysis has become a method of choice in the study of
      unbound tissue concentrations of both endogenous and exogenous substances.
      Microdialysis has been shown to offer information about substances directly at
      the site of action while being well tolerable and safe. The large variety of its
      field of application has been demonstrated. However, a few challenges have to be
      met to make this method generally applicable in routine applications. This review
      will provide an overview over theoretical aspects that have to be considered
      during the implementation of microdialysis. Moreover, a comparison between
      microdialysis and other tissue sampling techniques will demonstrate advantages
      and limitations of the methods mentioned. Subsequently, it will present a
      critical synopsis of a variety of scientific/biomedical applications of this
      method with emphasis on the most recent literature, focussing on target tissues
      while giving examples of substances examined. It is concluded that microdialysis
      will be of great value in future investigations of pharmacokinetics,
      pharmacodynamics and in monitoring of disease status and progression.

PMID- 15854797
TI  - Pharmacodynamic behaviour of the selective cyclooxygenase-2 inhibitor lumiracoxib
      in the lipopolysaccharide-stimulated rat air pouch model.
AB  - PURPOSE: To investigate the pharmacodynamic behaviour of the selective
      cyclooxygenase-2 inhibitor, lumiracoxib, in the rat air pouch. METHODS: Air
      pouches were injected with lipopolysaccharide to stimulate prostaglandin E2
      (PGE2) production 1h after lumiracoxib treatment. Pouch fluid samples were
      collected 6 or 24 h after lumiracoxib administration to measure PGE2 levels.
      Lumiracoxib concentrations in pouch fluid and plasma were measured by mass
      spectrometry. RESULTS: Oral administration of lumiracoxib resulted in dose
      dependent inhibition of PGE2 production 6 and 24 h post-dose. The estimated ED50
      values for inhibition of PGE2 production were 0.1 and 2.0 mg/kg at 6 and 24 h,
      respectively. Lumiracoxib concentrations in plasma and pouch fluid increased in
      proportion to dose. There was a strong positive correlation between lumiracoxib
      concentrations in plasma and pouch fluid compartments. Lumiracoxib concentrations
      were higher in plasma than in pouch fluid 6 h post-dose, but at 24 h post-dose,
      pouch fluid concentrations were > or =4-fold greater than plasma concentrations.
      CONCLUSIONS: Lumiracoxib readily enters the air pouch and persists in this
      extravascular compartment for a longer period of time than in plasma. This
      distribution profile may contribute to the ability of lumiracoxib to inhibit PGE2
      production up to 24 h after dosing.

PMID- 15854798
TI  - Chitosan-reinforced alginate microspheres obtained through the
      emulsification/internal gelation technique.
AB  - Alginate microspheres prepared by emulsification/internal gelation were chosen as
      carriers for a model protein, hemoglobin (Hb). Reinforced chitosan-coated
      microspheres were obtained by an uninterrupted method, in order to simplify the
      coating process, minimize protein losses during production and to avoid Hb escape
      under acidic conditions. Microspheres recovery was evaluated as well as its
      morphology by determination of Hb encapsulation efficiency and microscopic
      observation, respectively. The formation of chitosan membrane made of it
      interaction with alginate was assessed by DSC (differential scanning calorimetry)
      and FT-IR (Fourier-transform infrared spectrometry) studies. Spherical uncoated
      microspheres with a mean diameter of 20 microm and encapsulation efficiency above
      89% were obtained. Coated microspheres provided similar encapsulation efficiency
      but a higher mean diameter was obtained due to microspheres clumping during the
      coating step. Protein loss occurred mainly during emulsification rather than
      recovery. FT-IR and DSC together indicated electrostatic interactions between
      alginate carboxylate and chitosan ammonium groups as the main forces for complex
      formation. Hb release from microspheres showed a pH-dependent profile and was
      affected by chitosan coating. Under simulated gastric conditions, a total Hb
      burst release from uncoated microspheres was decreased with one-stage and two
      stage chitosan coatings (68% and 28%, respectively). At pH 6.8, the Hb release
      from coated microspheres was fast but incomplete. These results suggest an
      optimization of the coating method to protect Hb under acidic conditions and to
      permit a complete but sustained release of Hb.

PMID- 15854799
TI  - Melt sonocrystallization of ibuprofen: effect on crystal properties.
AB  - This study deals with development of melt sonocrystallization technique for
      ibuprofen agglomerates and characterization of their physicochemical,
      micromeritic and compressional properties. Melt sonocrystallization process was
      developed for ibuprofen in which ibuprofen melt was poured in deionized water
      maintained at 25 degrees C and simultaneously subjected to ultrasonic energy. The
      agglomerates obtained were evaluated using Scanning electron microscopy (SEM),
      Differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD),
      Fourier transformed infrared spectroscopy (FTIR), intrinsic dissolution rate, BET
      analysis, solubility, image analysis, Heckel plot analysis and friability
      studies. The irregular agglomerates with porous surface were obtained. The
      agglomerates comprised of crystals having different crystal habits such as
      needles, plates, and some hollow tubes. Solubility, specific surface area and
      intrinsic dissolution rate increased with the treatment of ultrasonic energy. SEM
      and XRPD confirmed crystal habit changes. Improvement in compressional properties
      and reduction in sticking was observed due to the change in crystal habit.
      Crystal habit changes and lattice defects during processing have caused favorable
      changes in the physicochemical and compressional properties of the drug.

PMID- 15854800
TI  - Characterization of the 13-cis-retinoic acid/cyclodextrin inclusion complexes by
      phase solubility, photostability, physicochemical and computational analysis.
AB  - 13-cis-Retinoic acid (13-cis-RA) is a synthetic retinoid commonly used in the
      treatment of severe acne. It has also been found to possess potential
      chemopreventive activity. It has extremely low aqueous solubility and high photo
      sensitivity. This study investigated the effects of the complexation of 13-cis-RA
      with alpha-cyclodextrin (alpha-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta
      CD) on its phase solubility. HP-beta-CD was found to be more effective in
      increasing the aqueous solubility of 13-cis-RA compared to alpha-CD. Phase
      solubility studies indicated that the solubility of 13-cis-RA was increased
      dramatically by the formation of inclusion complex with HP-beta-CD. The
      solubility was further enhanced by pH adjustment. The photostability of the
      selected inclusion complex of 13-cis-RA:HP-beta-CD was then evaluated.
      Complexation with HP-beta-CD was found to delay the photo-degradation of 13-cis
      RA in aqueous solution. The physicochemical properties of the solid inclusion
      complex were characterized by Fourier transform infrared spectroscopy (FTIR),
      differential scanning calorimetry (DSC), and X-ray diffractometry (XRD).
      Molecular modeling with MMFF94s force field (SYBYL V6.6) was utilized to predict
      the preferred orientation of 13-cis-RA in the CD cavity and the main structural
      features responsible for the enhancement of its solubility and photostability.
      The energy scores estimated from the computational analysis were found capable of
      reflecting the stability constants of the cyclodextrin complexes obtained in the
      phase solubility studies. The results showed that HP-beta-CD was a proper
      excipient for increasing solubility and stability of 13-cis-RA.

PMID- 15854801
TI  - Vanillin suppresses in vitro invasion and in vivo metastasis of mouse breast
      cancer cells.
AB  - Vanillin, a food flavoring agent, has been reported to show anti-mutagenic
      activity and to inhibit chemical carcinogenesis. In this study, we examined the
      effect of vanillin on the growth and metastasis of 4T1 mammary adenocarcinoma
      cells in BALB/c mice. Mice orally administered with vanillin showed significantly
      reduced numbers of lung metastasized colonies compared to controls. In vitro
      studies revealed that vanillin, at concentrations that were not cytotoxic,
      inhibited invasion and migration of cancer cells and inhibited enzymatic activity
      of MMP-9 secreted by the cancer cells. Vanillin also showed growth inhibitory
      effect towards cancer cells in vitro. However, vanillic acid, a major metabolic
      product of vanillin in human and rat, was not active in these in vitro activity
      assays. Our findings suggest that vanillin has anti-metastatic potential by
      decreasing invasiveness of cancer cells. Since vanillin is generally regarded as
      safe, it may be of value in the development of anti-metastatic drugs for cancer
      treatment.

PMID- 15854802
TI  - A new sunscreen of the cinnamate class: synthesis and enzymatic hydrolysis
      evaluation of glyceryl esters of p-methoxycinnamic acid.
AB  - Glyceryl esters of p-methoxycinnamic acid, 1,3-dipalmitoyl-2-p-methoxycinnamoyl
      1,2,3-propanetriol and 1,3-dioctanoyl-2-p-methoxycinnamoyl-1,2,3-propanetriol
      were synthesised in an attempt to increase substantivity and decrease eventual
      undesirable effects of sunscreens of this class. To assess if the glyceryl esters
      could present a higher stability towards hydrolysis by lipases in the stratum
      corneum, hydrolysis rates were determined in vitro using a commercial fungal
      lipase from Rhizomucor miehei. Results presented herein show that the glyceryl
      esters have similar lambda(max) and epsilon values to sunscreens of the cinnamate
      class. The ester 1,3-dipalmitoyl-2-p-methoxycinnamoyl-1,2,3-propanetriol
      presented a 2.8 times lower hydrolysis rate by lipase, in vitro, than the
      commercial sunscreen 2-ethylhexyl-p-methoxycinnamate (alkyl ester). This finding
      suggests that this triacylglycerol can possibly have a longer retention time in
      the skin and consequently promote a more intense and effective antisolar action
      than the commercial sunscreen.

PMID- 15854803
TI  - Characterization of the rotating dialysis cell as an in vitro model potentially
      useful for simulation of the pharmacokinetic fate of intra-articularly
      administered drugs.
AB  - The rotating dialysis cell consisting of a donor and an acceptor compartment with
      volumes of 10 and 1000 ml, respectively, separated by a dialysis membrane is
      proposed as an in vitro model potentially useful for simulation of the events
      influencing drug residence time in the knee joint cavity after intra-articular
      instillation. The purpose of this study was to characterize the rotating dialysis
      cell model with respect to basic model and drug related factors affecting the
      rate of drug appearance in the acceptor phase after initial instillation of the
      solutes into the donor cell. A total of 15 model compounds were included in the
      study and it was revealed that the transport processes were governed by (i) the
      volume of the donor solution and (ii) the molecular weight of the diffusants. A
      relationship between the donor volume-independent permeability coefficient and
      the molecular weight of the diffusants has been established. Additionally, the
      model was robust with release kinetics being insensitive to changes in pH, ionic
      strength, viscosity of the release medium, and revolution speed of the donor
      cell. The characteristics of the rotating dialysis cell model suggest that it may
      be a useful tool in the design of innovative depot injectables in the area of
      local joint delivery.

PMID- 15854804
TI  - Atomic force microscopy and photon correlation spectroscopy: two techniques for
      rapid characterization of liposomes.
AB  - The direct evaluation of the heterogeneity of the particle population of
      nanometric drug delivery systems as liposomes is difficult to achieve owing to
      the dimension and the carrier characteristics. The influence of the lipidic ratio
      and composition on the physical stability of liposomes during their storage was
      investigated using atomic force microscopy (AFM) and photon correlation
      spectroscopy (PCS). Liposomes were made by a mixture of different lipids and
      obtained using distinct methods of preparation. AFM images, acquired immediately
      after the deposition of the sample on mica surface, clearly showed the spherical
      shape of the lipidic vesicles. In all the 7 months of the experiment, the average
      sizes of the different liposomes evaluated using the two techniques were
      comparable. According to PCS analysis, AFM images confirmed that almost all the
      diversified vesicular systems tended to form aggregates during their storage;
      this loss of stability was strengthened by the increase of polydispersity index
      value. The different behaviours observed were to ascribe to the lipidic
      composition more than the methods of liposome preparation. In conclusion, AFM
      technique owing to the relative simplicity cold be useful for the technological
      control of size distribution profile according to the preparative factors and
      moreover to the batch-to-batch reproducibility.

PMID- 15854805
TI  - Tissue distribution, pharmacokinetics and identification of roscovitine
      metabolites in rat.
AB  - The pharmacokinetics, biodistribution and the metabolic pathway of roscovitine
      were investigated in Sprague-Dawley rats after a single intravenous dose of 25
      mg/kg. Blood, lungs, kidney, liver, testis, adipose tissue, spleen and brain were
      removed at different time-points. Plasma and tissue samples were analyzed using
      high performance liquid chromatography. The metabolites were identified using
      liquid chromatography/tandem mass spectrometry and nuclear magnetic resonance
      spectroscopy. Roscovitine (MW=354) was cleared rapidly from circulation and
      highly distributed to the tissues. The elimination half-life of roscovitine in
      plasma and tissues was short (<30 min). A major metabolite (M1) was observed
      mainly in plasma and in lower levels in all other tissues. M1 was identified as
      conversion of the hydroxyl-group at C2 to carboxylic acid (MW=368). A second
      metabolite (M2) was observed mainly in liver and kidney and identified as a
      hydroxylation product of the C8 of the purine-ring (MW=370). A third metabolite
      (M3) was found in several organs and corresponded to N-dealkylation of the N9
      isopropyl side-chain (MW=312). Roscovitine concentrations in the brain were 30%
      of that observed in plasma, however no metabolites were detected in brain. In
      this investigation, three major metabolites of roscovitine were isolated and
      identified. Also, it was shown that roscovitine eliminates rapidly from both
      blood and tissues.

PMID- 15854806
TI  - A solid-state NMR study of molecular mobility and phase separation in co-spray
      dried protein-sugar particles.
AB  - Molecular mobility and physical form of co-spray-dried sugar-lysozyme
      formulations were evaluated. Co-spray-dried trehalose:lysozyme and
      sucrose:lysozyme formulations in 1:9, 1:1 and 9:1 ratios (w:w) were stored at 0%
      RH and 75% RH for 5-6 days. Molecular mobility and physical form of the co-spray
      dried formulations after storage were determined by using 13C and 1H solid-state
      NMR as well as X-ray powder diffractometry. The results showed that increasing
      sugar content in co-spray-dried formulations stored at 0% RH decreased molecular
      mobility of the amorphous formulations indicating a close association of the
      protein and sugar. Exposure of sugar-lysozyme 1:1 and 9:1 formulations to 75% RH
      led to separation of sugar and protein phases, where the sugar phase was
      crystalline. The intimate sugar-lysozyme interaction of the formulations stored
      at 0% RH and the phase separation of the sugar-rich formulations stored at 75% RH
      were also confirmed by using 13C solid-state NMR spin-lattice relaxation time
      filter (T1-filter) measurements. The propensity of sucrose and trehalose to
      crystallise was similar; however, the results suggest that part of the sugar in
      the phase-separated formulations remained amorphous and in close association with
      lysozyme.

PMID- 15854807
TI  - Permeability of pig urinary bladder wall: the effect of chitosan and the role of
      calcium.
AB  - Chitosan is a cationic polysaccharide widely employed as an absorption enhancer.
      The aim of this work was to examine the effect of chitosan on the permeability of
      isolated pig urinary bladder wall as well as to determine the role of calcium
      ions in this process. Besides permeability studies, scanning electron microscopy
      and fluorescent microscopy were applied to get an insight into the mechanism by
      which chitosan increases the permeability of urinary bladder wall. Additionally,
      the obtained findings were compared to the mechanism proposed for Caco-2 cells.
      The results show that 0.5% (w/v) chitosan increases the permeability of urinary
      bladder wall by causing the desquamation of the urothelium. Calcium ions, when
      applied to the luminal surface of the urinary bladder at the same time as
      chitosan, decreases the effect of chitosan on permeation of the model drug
      moxifloxacin into the bladder wall in concentration dependent way. The
      desquamation of urothelium cells caused by chitosan was reduced in the presence
      of calcium, but not to such extent as it would be expected from the permeability
      studies. When present, calcium obviously interferes directly in the interactions
      between chitosan and the surface of urothelium.

PMID- 15854808
TI  - Estimation of dosing strategies aiming at maximizing utility or responder
      probability, using oxybutynin as an example drug.
AB  - Methods for optimizing dosing strategies for individualization with a limited
      number of discrete doses, in terms of maximizing the expected utility of
      treatment or responder probability, are presented. The optimality criteria
      require models for both beneficial and adverse effects that are part of the
      utility definition and published population models describing those effects for
      oxybutynin (urge urinary incontinence episodes per week and severity of dry
      mouth, respectively) were used for illustration. Dosing strategies with two
      dosing categories were defined in terms of sizes of the daily doses (low and high
      dose) and the proportion of patients that can be expected to be preferentially
      treated at the low dose level. Utility and responder definitions were varied to
      investigate the influence on the resulting dosing strategy. By minimizing a risk
      function, describing the seriousness of deviations from the predefined target,
      optimal dosing strategies were estimated using mixture models in NONMEM. The
      estimated dose ranges for oxybutynin were similar to those recommended. The
      optimal individualization conditions were dependent on the definitions of
      responder and utility. The predicted gain of individualization given utility and
      responder definitions used was greater, when a responder criteria was maximized
      compared with maximizing utility.

PMID- 15854809
TI  - A comparative study of the potential of solid triglyceride nanostructures coated
      with chitosan or poly(ethylene glycol) as carriers for oral calcitonin delivery.
AB  - We have previously reported the formation and characterization of poly(ethylene
      glycol) (PEG)-coated and chitosan (CS)-coated lipid nanoparticles. In the present
      work our goal was to study the interaction of these surface-modified lipid
      nanoparticles with Caco-2 cells and to evaluate the potential of these
      nanostructures as oral delivery systems for salmon calcitonin (sCT). The
      interaction of rhodamine-loaded nanoparticles with the Caco-2 cell monolayers was
      evaluated quantitatively and qualitatively by confocal laser scanning microscopy
      and fluorimetry, respectively. The ability of these nanoparticles to reversibly
      enhance the transport of hydrophilic macromolecules through the monolayers was
      investigated by measuring the transepithelial electric resistance and the
      permeability to Texas Red-dextran. Finally, in vivo studies of the response to
      sCT-loaded nanoparticles were performed in rats. The results showed that the
      association of rhodamine-loaded nanoparticles to the Caco-2 cell monolayer was
      independent of the surface coating of the nanoparticles (CS-coated versus PEG
      coated nanoparticles). However, while PEG-coated nanoparticles did not affect the
      permeability of Caco-2 monolayers, CS-coated nanoparticles produced a dose
      dependent reduction in the transepithelial electric resistance, simultaneously to
      an enhanced dextran transport. The results obtained following oral administration
      of sCT-loaded CS-coated nanoparticles to rats showed a significant and prolonged
      reduction in the serum calcium levels as compared to those obtained for control
      (sCT solution). In contrast, the hypocalcemic response of sCT-loaded PEG-coated
      nanoparticles was not significantly different of that provided by the control
      (sCT solution). Therefore, these results indicate that the surface composition of
      the particles is a key factor in the improvement of the efficiency of oral sCT
      formulations. Moreover, the encouraging results obtained for CS-coated
      nanoparticles underline their potential as carriers for peptide delivery.

PMID- 15854810
TI  - Pyrimidine and nucleoside gamma-esters of L-Glu-Sar: synthesis, stability and
      interaction with hPEPT1.
AB  - The aim of the present study was to improve the synthetic pathway of
      bioreversible dipeptide derivatives as well as evaluate the potential of using l
      Glu-Sar as a pro-moiety for delivering three newly synthesised nucleoside and
      pyrimidine l-Glu-Sar derivatives. l-Glu(trans-2-thymine-1-yl-tetrahydrofuran-3-yl
      ester)-Sar (I), l-Glu(thymine-1-yl-methyl ester)-Sar (II) and l
      Glu(acyclothymidine)-Sar (III) were synthesised and in vitro stability was
      studied in various aqueous and biological media. Affinity to and translocation
      via hPEPT1 was investigated in mature Caco-2 cell monolayers, grown on permeable
      supports. Affinity was estimated in a competition assay, using [14C] labelled Gly
      Sar (glycylsarcosine). Translocation was measured as pHi-changes induced by the
      substrates using the fluorescent probe BCECF and an epifluorescence microscope
      setup. All dipeptide derivatives released the model drugs quantitatively by
      specific base-catalysed hydrolysis at pH>6.0. II was labile in aqueous buffer
      solution, whereas I and III showed appropriate stability for oral administration.
      In 10% porcine intestinal homogenate, the half-lives of the dipeptide derivatives
      indicated limited enzyme catalyzed degradation. All compounds showed good
      affinity to hPEPT1, but the Compounds I and III showed not to be translocated by
      hPEPT1. The translocation of the l-Glu-Sar derivative of acyclovir, l
      Glu(acyclovir)-Sar was also investigated and showed not to take place.
      Consequently, l-Glu-Sar seems to be a poor pro-moiety for hPEPT1-mediated
      transport.

PMID- 15854811
TI  - A simple method for differentiation of monoisotopic drug metabolites with
      hydrogen-deuterium exchange liquid chromatography/electrospray mass spectrometry.
AB  - A simple but efficient method for determination of labile protons in drug
      metabolites using post-column infusion of deuterium oxide (D2O) in liquid
      chromatography/mass spectrometry (LC/MS) experiments with electrospray ionization
      and time-of-flight mass spectrometry is described. The number of exchangeable
      protons in analytes, i.e. hydroxyl, amine, thiol and carboxylic acid protons, can
      easily be determined by comparing the increase in m/z values after H/D-exchange
      occurring online between a HPLC column and electrospray ion source. Especially,
      the hydroxyl metabolites and S/N-oxides with the same accurate mass can be
      distinguished. A good degree of exchange was obtained in repeatable experiments.
      Only a low consumption of D2O is needed in a very easy and rapidly set-up
      procedure. The method is applied in the study of metabolites of omeprazole and
      imipramine in human and mouse in vitro samples, respectively, together with exact
      mass data obtained from time-of-flight mass spectrometric experiments.

PMID- 15854812
TI  - Pharmacokinetic-pharmacodynamic modelling of the schedule-dependent effect of the
      anti-cancer agent CHS 828 in a rat hollow fibre model.
AB  - N-(6-Chlorophenoxyhexyl)-N'-cyano-N''-4-pyridylguanidine (CHS 828) is a novel
      anticancer agent that shows schedule-dependent effects in vitro and in vivo, as
      well as in Phase I clinical trials. A rat hollow fibre model was used to
      investigate whether this dependency is due to pharmacokinetic and/or
      pharmacodynamic factors. The effect on two cell lines, MDA-MB-231 (breast cancer)
      and CCRF-CEM (leukaemia) were studied after CHS 828 was administered orally as a
      single dose or in a 5-day schedule, at different total dose levels. The 5-day
      schedules were associated with greater effects on both cell lines compared with
      single doses. A one-compartment pharmacokinetic model, with a half-life of 2.3h
      and a consecutive zero- and first-order process to describe dissolution and
      absorption, fit the concentration data. Pharmacokinetics were dose-dependent, as
      the fraction absorbed decreased with increasing dose. Clearance increased with
      accumulative exposure. Twenty hours after administration, concentrations started
      to increase again, probably due to coprophagy. Pharmacokinetic-pharmacodynamic
      models characterized the cell growth and cell kill over time and showed that
      schedule-dependent antitumour effects were present also when the dose-dependent
      pharmacokinetics were accounted for. The prolonged schedules of CHS 828 were
      therefore associated with greater antitumour effects than single doses of the
      same total exposure.

PMID- 15854814
TI  - Biosensors for real-time in vivo measurements.
AB  - The current status of sensors capable of continuous measurement of analytes in
      biological media is reviewed. This review containing 173 references deals with
      devices whose use in single cells, tissue slices, animal models and humans has
      been demonstrated. In addition to sensors specific for glucose, lactate,
      glutamate, pyruvate, choline and acetylcholine, insights obtained from monitoring
      nitric oxide, Na(+), K(+), Ca(2+), and dopamine are presented. Performance
      criteria for sensor performance are described as is the subject of biosensor
      calibration. Biocompatibility issues are dealt with in some detail as is the
      status of continuous blood glucose monitoring in humans.

PMID- 15854815
TI  - Systems Biology-an interdisciplinary approach.
AB  - System-level approaches in biology are not new but foundations of "Systems
      Biology" are achieved only now at the beginning of the 21st century [Kitano, H.,
      2001. Foundations of Systems Biology. MIT Press, Cambridge, MA]. The renewed
      interest for a system-level approach is linked to the progress in collecting
      experimental data and to the limits of the "reductionist" approach. System-level
      understanding of native biological and pathological systems is needed to provide
      potential therapeutic targets. Examples of interdisciplinary approach in Systems
      Biology are described in U.S., Japan and Europe. Robustness in biology, metabolic
      engineering and idiotypic networks are discussed in the framework of Systems
      Biology.

PMID- 15854816
TI  - Cytochrome P450 biosensors-a review.
AB  - Cytochrome P450 (CYP) is a large family of enzymes containing heme as the active
      site. Since their discovery and the elucidation of their structure, they have
      attracted the interest of scientist for many years, particularly due to their
      catalytic abilities. Since the late 1970s attempts have concentrated on the
      construction and development of electrochemical sensors. Although sensors based
      on mediated electron transfer have also been constructed, the direct electron
      transfer approach has attracted most of the interest. This has enabled the
      investigation of the electrochemical properties of the various isoforms of CYP.
      Furthermore, CYP utilized to construct biosensors for the determination of
      substrates important in environmental monitoring, pharmaceutical industry and
      clinical practice.

PMID- 15854817
TI  - Analytical applications of aptamers.
AB  - So far, several bio-analytical methods have used nucleic acid probes to detect
      specific sequences in RNA or DNA targets through hybridisation. More recently,
      specific nucleic acids, aptamers, selected from random sequence pools, have been
      shown to bind non-nucleic acid targets, such as small molecules or proteins. The
      development of in vitro selection and amplification techniques has allowed the
      identification of specific aptamers, which bind to the target molecules with high
      affinity. Many small organic molecules with molecular weights from 100 to 10,000
      Da have been shown to be good targets for selection. Moreover, aptamers can be
      selected against difficult target haptens, such as toxins or prions. The selected
      aptamers can bind to their targets with high affinity and even discriminate
      between closely related targets. Aptamers can thus be considered as a valid
      alternative to antibodies or other bio-mimetic receptors, for the development of
      biosensors and other analytical methods. The production of aptamers is commonly
      performed by the SELEX (systematic evolution of ligands by exponential
      enrichment) process, which, starting from large libraries of oligonucleotides,
      allows the isolation of large amounts of functional nucleic acids by an iterative
      process of in vitro selection and subsequent amplification through polymerase
      chain reaction. Aptamers are suitable for applications based on molecular
      recognition as analytical, diagnostic and therapeutic tools. In this review, the
      main analytical methods, which have been developed using aptamers, will be
      discussed together with an overview on the aptamer selection process.

PMID- 15854818
TI  - Home blood glucose biosensors: a commercial perspective.
AB  - Twenty years on from a review in the first issue of this journal, this
      contribution revisits glucose sensing for diabetes with an emphasis on commercial
      developments in the home blood glucose testing market. Following a brief
      introduction to the needs of people with diabetes, the review considers defining
      technologies that have enabled the introduction of commercial products and then
      reviews the products themselves. Drawing heavily on the performance of actual
      instruments and publicly available information from the companies themselves,
      this work is designed to complement more conventional reviews based on papers
      published in scholarly journals. It focuses on the commercial reality today and
      the products that we are likely to see in the near future.

PMID- 15854819
TI  - Nanoparticle labels in immunosensing using optical detection methods.
AB  - Efforts to improve the performance of immunoassays and immunosensors by
      incorporating different kinds of nanostructures have gained considerable momentum
      over the last decade. Apart from liposomes, which will not be discussed here,
      most groups focus on artificial, particulate marker systems, both organic and
      inorganic. The underlying detection procedures may be based either on electro
      magnetical or optical techniques. This review will be confined to the latter
      only, comprising nanoparticle applications generating signals as diverse as
      static and time-resolved luminescence, one- and two-photon absorption, Raman and
      Rayleigh scattering as well as surface plasmon resonance and others. In general,
      all endeavors cited are geared to achieve one or more of the following goals:
      lowering of detection limits (if possible, down to single-molecule level),
      parallel integration of multiple signals (multiplexing), signal amplification by
      several orders of magnitude and prevention of photobleaching effects with
      concomitant maintenance of antigen binding specificity and sensitivity. Inorganic
      nanoparticle labels based on noble metals, semiconductor quantum dots and
      nanoshells appear to be the most versatile systems for these bioanalytical
      applications of nanophotonics.

PMID- 15854820
TI  - Evanescent wave fluorescence biosensors.
AB  - Since discovery and first use in the mid-1970s, evanescent wave fluorescence
      biosensors have developed into a diverse range of instruments, each designed to
      meet a particular detection need. In this review, we provide a brief synopsis of
      what evanescent wave fluorescence biosensors are, how they work, and how they are
      used. In addition, we have summarized the important patents that have impacted
      the evolution from laboratory curiosities to fully automated commercial products.
      Finally, we address the critical issues that evanescent wave fluorescence
      biosensors will face in the coming years.

PMID- 15854821
TI  - Microfluidic immunosensor systems.
AB  - Immunosensing microfluidic devices are reviewed. Devices are commonly fabricated
      in glass, silicon, and polymers, with polymers seeing greater attention in recent
      years. Methods have been developed to immobilize antibodies and other molecules
      and resist non-specific adsorption through surface modification. The most common
      detection method is fluorescence, followed by electrochemistry. Various
      microfluidic designs have been reported for immunoassay applications. The
      observed trends in microfluidic immunoassay applications closely resemble the
      trends of general immunoassays, where large molecules are detected principally
      through a sandwich procedure, while competitive assays are used to detect smaller
      molecules. The following future trends are suggested: more sensitive detection,
      increased integration and miniaturization, multianalyte analysis, more robust
      reagents and devices, and increased functionality of surface treatments.

PMID- 15854823
TI  - Biosensors-a perspective.
AB  - Biosensors have been under development for over 35 years and research in this
      field has become very popular for 15 years. Electrochemical biosensors are the
      oldest of the breed, yet sensors for only one analyte (glucose) have achieved
      widespread commercial success at the retail level. This perspective provides some
      cautions related to expectations for biosensors, the funding of science, and the
      wide gap between academic and commercial achievements for sensor research. The
      goal of this commentary is not to arrive at any particular truth, but rather to
      stimulate lively discussion.

PMID- 15854822
TI  - Genetically encoded optical probes for imaging cellular signaling pathways.
AB  - The intracellular signaling can be monitored in vivo in living cells by
      genetically encoded intracellular fluorescent and bioluminescent probes or
      indicators, which include second messengers, protein phosphorylation, protein
      conformational changes, protein-protein interactions, and protein localizations.
      These probes are of general use not only for fundamental biological studies, but
      also for assay and screening of possible pharmaceutical or toxic chemicals that
      inhibit or facilitate cellular signaling pathways. In this review, two examples
      of such indicators were briefly introduced. First, a genetically encoded
      fluorescent indicator was described for the detection and characterization of
      estrogen agonists and antagonists. The indicator was named SCCoR (single cell
      coactivator recruitment). The high sensitivity of the present indicator made it
      possible to distinguish between estrogen strong and weak agonists in a dose
      dependent fashion, immediately after adding a ligand to live cells.
      Discrimination of agonists from antagonists was efficiently achieved using the
      indicator. The approach described here can be applied to develop biosensors for
      other hormone receptors as well. Another example herein is a genetically encoded
      bioluminescent indicator for monitoring the nuclear trafficking of target
      proteins in vitro and in vivo. We demonstrated quantitative cell-based in vitro
      sensing of ligand-induced translocation of androgen receptor, which allowed high
      throughput screening of exo- and endogenous agonists and antagonists.
      Furthermore, the indicator enabled noninvasive in vivo imaging of the androgen
      receptor translocation in the brains of living mice with a charge-coupled device
      imaging system. These rapid and quantitative analyses in vitro and in vivo
      provide a wide variety of applications for screening pharmacological or
      toxicological compounds and testing them in living animals.

PMID- 15854824
TI  - Direct electron transfer between copper-containing proteins and electrodes.
AB  - The electrochemistry of some copper-containing proteins and enzymes, viz. azurin,
      galactose oxidase, tyrosinase (catechol oxidase), and the "blue" multicopper
      oxidases (ascorbate oxidase, bilirubin oxidase, ceruloplasmin, laccase) is
      reviewed and discussed in conjunction with their basic biochemical and structural
      characteristics. It is shown that long-range electron transfer between these
      enzymes and electrodes can be established, and the mechanistic schemes of the DET
      processes are proposed.

PMID- 15854825
TI  - Fluorescence-based glucose sensors.
AB  - There is an urgent need to develop technology for continuous in vivo glucose
      monitoring in subjects with diabetes mellitus. Problems with existing devices
      based on electrochemistry have encouraged alternative approaches to glucose
      sensing in recent years, and those based on fluorescence intensity and lifetime
      have special advantages, including sensitivity and the potential for non-invasive
      measurement when near-infrared light is used. Several receptors have been
      employed to detect glucose in fluorescence sensors, and these include the lectin
      concanavalin A (Con A), enzymes such as glucose oxidase, glucose dehydrogenase
      and hexokinase/glucokinase, bacterial glucose-binding protein, and boronic acid
      derivatives (which bind the diols of sugars). Techniques include measuring
      changes in fluorescence resonance energy transfer (FRET) between a fluorescent
      donor and an acceptor either within a protein which undergoes glucose-induced
      changes in conformation or because of competitive displacement; measurement of
      glucose-induced changes in intrinsic fluorescence of enzymes (e.g. due to
      tryptophan residues in hexokinase) or extrinsic fluorophores (e.g. using
      environmentally sensitive fluorophores to signal protein conformation). Non
      invasive glucose monitoring can be accomplished by measurement of cell
      autofluorescence due to NAD(P)H, and fluorescent markers of mitochondrial
      metabolism can signal changes in extracellular glucose concentration. Here we
      review the principles of operation, context and current status of the various
      approaches to fluorescence-based glucose sensing.

PMID- 15854826
TI  - Rapid analysis of fatty acid-binding proteins with immunosensors and immunotests
      for early monitoring of tissue injury.
AB  - Fatty acid-binding protein (FABP) holds promise for early detection of tissue
      injury. This small protein (15kD) appears earlier in the blood than large
      proteins after cell damage. Combined its characteristics of high concentration
      tissue contents and low normal plasma values provide the possibility of a rapid
      rise above the respective reference values, and thus an early indication of the
      appearance of tissue injury. A general review was presented on the current status
      of different types of FABP for the detection of tissue injury in patients with
      myocardial injury, brain injury and also in athletes or horses with skeletal
      muscle injury. To take full advantage of the characteristics of the early marker
      FABP, rapid analysis is a crucial parameter. In this review, an overview of the
      development of immunoassay for the quantification of FABP in buffer, plasma or
      whole blood was outlined. The characteristics of different FABP immunosensors and
      immunotests were described. The feasibility of these immunoassays to be used in
      routine clinical practice and in emergency case was also discussed. Nowadays, the
      improved automated immunoassays (e.g. a microparticle-enhanced turbidimetric
      immunoassay), less time-consuming bedside immunosensors and immunotests (e.g. a
      one-step FABP lateral flow immunotest), are the main advance technology in point
      of-care testing. With these point-of-care tests, the application of FABP as an
      early tissue injury marker has a great potential for many clinical purposes.

PMID- 15854827
TI  - Cyanide fishing and cyanide detection in coral reef fish using chemical tests and
      biosensors.
AB  - Sodium cyanide has been used in the Philippines to collect tropical marine fish
      for aquarium and food trades since the early 1960s. Cyanide fishing is a fast
      method to stun and collect fish. This practice is damaging the coral reefs
      irreversibly. In most countries cyanide fishing is illegal, but most of the
      exporting and importing countries do not have test and certificate systems. Many
      analytical methods are available for the detection of cyanide in environmental
      and biological samples. However, most of the techniques are time consuming, and
      some lack specificity or sensitivity. Besides, an ultra sensitive cyanide
      detection method is needed due to the rapid detoxification mechanisms in fish.
      The aim of this review is to give an overview of cyanide fishing problem in the
      south-east Asia and current strategies to combat this destructive practice,
      summarise some of the methods for cyanide detection in biological samples and
      their disadvantages. A novel approach to detect cyanide in marine fish tissues is
      briefly discussed.

PMID- 15854828
TI  - Molecular cloning and characterisation of a Rab-binding GDP-dissociation
      inhibitor from Medicago truncatula.
AB  - We have isolated and sequenced the full-length cDNA of a GDP-dissociation
      inhibitor (GDI) from the model legume Medicago truncatula L. The cDNA (MtGDI)
      contains an open reading frame of 1335 bp, coding for a protein of 444 amino
      acids with a calculated molecular mass of 49,785 kDa. The deduced amino acid
      sequence shows significant homology to other plant GDIs, the highest homology
      being found to GDI from the legume Cicer arietinum (96% identity). The MtGDI was
      expressed as a N-terminal FLAG-fusion protein in Escherichia coli BL21 (DE3). Its
      direct interaction with a small G protein of Rab type from Medicago sativa,
      MsRab11f, was demonstrated in vitro by co-immunoprecipitation using a peptide
      specific antibody raised against MtGDI. The dissociation constant of the MtGDI
      MsRab11f complex (4 muM) was determined by a surface plasmon resonance (SPR)
      assay. Real-time RT-PCR and Western blot analyses suggested that MtGDI is
      ubiquitously expressed in M. truncatula. High levels of MtGDI mRNA were detected
      in uninfected roots, leaves and root nodules. In etiolated seedlings and cell
      cultures, the amount of MtGDI mRNA was much lower. In all tissues tested, the
      peptide-specific anti-MtGDI antibody detected the expected 50 kDa protein in the
      total protein extracts. MtGDI was found in the cytosol; however, a significant
      fraction was associated with the intracellular membranes in seedlings and roots
      indicating a membrane localisation of the protein. A second immunoreactive band
      was detected in leaves suggesting that more than one GDI isoform exist in M.
      truncatula.

PMID- 15854829
TI  - Effects of temperature on oxidative stress defense systems, lipid peroxidation
      and lipoxygenase activity in Phalaenopsis.
AB  - Higher plants growing in natural environments experience various abiotic
      stresses. The aim of this study was to determine whether exposure to temperature
      stress would lead to oxidative stress and whether this effect varied with
      different exposure periods. The thermal dependencies of the activities of
      protective enzymes, photosynthetic efficiency (Fv/Fm), protein, non-protein thiol
      (NP-SH), cysteine content, lipoxygenase (LOX) activity (EC 1.13.11.12) and
      malondialdehyde (MDA) content at 25-40 degrees C were determined for 4, 24 and 48
      h in leaf and root segments of Phalaenopsis. The increase in MDA level and LOX
      activity may be due to temperature-associated oxidative damage to leaf and root
      segments. Temperature-stress induced not only activities of active oxygen species
      (AOS) scavenging enzymes but also protein, NP-SH and cysteine content in both
      leaf and root segments at 30 degrees C for 4 and 24 h (except for 48 h in some
      cases) compared to 25 degrees C-and greenhouse-grown leaf and root segments
      indicating that antioxidants enzymes played an important role in protecting plant
      from temperature-stress. However, activities of dehydroascorbate reductase (DHAR,
      EC 1.8.5.1), glutathione peroxidase (GPX, EC 1.11.1.9) and glutathione-S
      transferase (GST, EC 2.5.1.18) in leaf and root, glutathione reductase (GR, EC
      1.6.4.2) in leaf and guaiacol peroxidase (G-POD, 1.11.1.7) in root segments were
      induced significantly at 40 degrees C compared to 25 degrees C and greenhouse
      grown plants suggesting that these enzymes play protective roles at high
      temperature. In contrast, activities of superoxide dismutase (SOD, EC 1.15.1.1)
      and monodehydroascorbate reductase (MDHAR, EC 1.6.5.4) in leaf and root, catalase
      (CAT, EC 1.11.1.6) in root, GR in root, and protein, cysteine, NP-SH content in
      both root and leaf and Fv/Fm ratio were diminished significantly at 40 degrees C
      compared to 25 degrees C-and greenhouse-grown plants. These indicate that these
      enzymes were apparently not involved in detoxification process and sensitive at
      higher temperature. Also, the close relation between activities of enzymes with
      their metabolites at 30 degrees C than 40 degrees C indicated that the
      antioxidants enzymes and metabolites both may play an important role in
      protecting cells against the temperature-stress.

PMID- 15854830
TI  - Treatment of pea pods with Bruchin B results in up-regulation of a gene similar
      to MtN19.
AB  - Differential display was used to examine changes in gene expression that resulted
      from treatment of pea (Pisum sativum L.) with Bruchin B. This lipid-derived
      regulator, one of several closely related compounds collectively referred to as
      bruchins, is an insect elicitor that causes localized cell division and callus
      formation when applied to pods of pea and certain other legumes. A DNA fragment
      that was prominently displayed after bruchin treatment was cloned and sequenced,
      and a full-length cDNA was obtained. This cDNA exhibited a high degree of
      sequence similarity to a gene, MtN19, expressed in root nodules of Medicago
      truncatula Gaertn. MtN19 codes for a putative protein of unknown function that is
      similar in sequence to predicted proteins from a number of other plant species,
      both leguminous and non-leguminous. Quantitative real-time PCR showed that the
      expression of this MtN19-like gene was significantly up-regulated within 1.5 h of
      bruchin treatment, and increased more than 100-fold within 6 h of treatment.
      Given the rapid and strong up-regulation after exposure of pods to a bruchin, it
      is likely that this gene plays an important role in the response of pea to these
      insect elicitors.

PMID- 15854831
TI  - Isolation and identification of a cold-inducible gene encoding a putative DRE
      binding transcription factor from Festuca arundinacea.
AB  - A new DRE-binding protein gene FaDREB1 encoded for an AP2/ERFBP-type
      transcription factor was isolated by RACE-PCR from Festuca arundinacea Schreb
      seedlings. Its cDNA was sequenced with 988 bp, from which a protein with 216
      amino acid residues was deduced with a predicted molecular mass of 23.479 kDa and
      a pI of 4.70. A search of the Protein Blast data revealed that this protein can
      be classified as a typical member of the AP2/EREBP family of DNA-binding
      proteins. The tissue organ-specific expression pattern of the FaDREB1 gene showed
      that its transcripts were abundant in leaves and leaf sheaths, and scarce in
      roots. Southern blot analysis indicated that it is a multiple-copy gene. Its mRNA
      accumulation profiles made clear that its expression was strongly induced by cold
      treatment, weakly induced by drought and salt stress, but did not respond to ABA
      treatment. It was concluded that the protein FaDREB1 may be involved in the
      process of plant response to cold stress through an ABA-independent pathway.

PMID- 15854832
TI  - Effect of water and temperature stress on the content of active constituents of
      Hypericum brasiliense Choisy.
AB  - Hypericum brasiliense is a medicinal herb containing several compounds with
      important pharmacological activity. In this study, we investigated the effects of
      water stress (waterlogging and drought) and temperature (low and high, constant
      and alternate) on the content of betulinic acid and phenolic compounds
      (quercetin, rutin, 1,5-dihydroxyxanthone, isouliginosin B) in this species. In
      general, the water stress increased the levels of all of the compounds analyzed,
      particularly some of the phenolic compounds. On the other hand, the responses to
      alternating temperatures varied according to the compound. The results for plants
      kept in growth chambers indicated that low light intensity might have influenced
      the levels of the compounds. There was also a reallocation of carbon, with water
      stressed plants showing a reduction in growth while the levels of the compounds
      increased. In the temperature treatments, such an increase was evident only for
      the phenolic compounds.

PMID- 15854833
TI  - Identification of tobacco ESTs with a hypersensitive response (HR)-specific
      pattern of expression and likely involved in the induction of the HR and/or
      localized acquired resistance (LAR).
AB  - Plant defense responses against pathogens often involve the restriction of the
      pathogen to its site of penetration. Restriction is achieved through the combined
      effects of the hypersensitive response (HR) and its tightly connected localized
      acquired resistance (LAR). As LAR is induced by unknown signals released by the
      cells undergoing the HR, LAR inducing/regulating genes must show a HR-specific
      pattern of expression. Here, we describe a differential display reverse
      transcript polymerase chain reaction (DDRT-PCR) strategy to isolate tobacco
      expressed sequence tags (ESTs) characterized by such an expression profile, which
      also characterizes genes involved in the induction/execution of the HR. We
      compared the DDRT-PCR profile of tobacco cell suspensions treated with beta
      megaspermin inducing the HR with that of untreated cells and cells treated with
      alpha-megaspermin inducing a Defense No Death (DND) phenotype. The expression
      profile of the selected ESTs was analyzed in tobacco plants expressing a beta
      megaspermin-induced HR or a DND phenotype, including LAR, induced by three
      different elicitors. This comprehensive analysis allowed to identify 24 HR
      specific ESTs, half of them shows no or non-significant homology with ESTs and
      genes in the databases. The other half exhibits homology with genes encoding a
      receptor-like kinase protein, proteins involved in the regulation of plasma
      membrane structure, proteins of the ubiquitin/26S proteasome proteolytic system,
      RNA binding proteins, and a protein hypothesized to be a true regulator of the
      HR.

PMID- 15854834
TI  - Effects of different cultivation temperatures on plasma membrane ATPase activity
      and lipid composition of sugar beet roots.
AB  - Sugar beet seedlings (Beta vulgaris L. cv. Monohill) were cultivated for 3 weeks
      at different root and shoot temperatures and the plasma membranes (PM) from roots
      were purified by aqueous two-phase partitioning and analyzed for lipid
      composition and ATPase activities. Lipid analyses, undertaken immediately after
      PM purification from the roots, showed that a low root zone temperature (10
      degrees C) decreased the ratio between the major lipids phosphatidylcholine (PC)
      and phosphatidylethanolamine (PE). A low temperature in the root environment
      increased the mol% of PE and decreased the mol% of phosphatidic acid (PA),
      independent on the shoot growth temperature. A low temperature also decreased the
      mol% of linoleic acid (18:2) and increased mol% of linolenic acid (18:3) in the
      analyzed lipid classes, especially in PC and PE. The ratio between acyl chain
      lipids and protein generally increased in PM from roots grown at 10 degrees C,
      compared with higher temperature. The changes in lipid composition correlated
      with changes in ATPase activities, detected as hydrolyses of MgATP. The kinetic
      parameters, K(m) and V of the PM H(+)ATPase in roots increased at a low
      cultivation temperature, independent on shoot temperature. Moreover, Arrhenius
      analyses showed that the transition temperature was independent of both root or
      shoot growth temperature at 10-24 degrees C, whereas the activation energy of the
      ATPase was dependent on the growth temperature of the root, and independent on
      shoot temperature. Thus, acclimation processes can take place in roots,
      irrespective of the shoot temperature.

PMID- 15854835
TI  - Conservation of the drought-inducible DS2 genes and divergences from their ASR
      paralogues in solanaceous species.
AB  - The drought-inducible DS2 genes of potatoes are members of the ASR (abscisic
      acid, stress and ripening) gene family. Previously it was shown that expression
      of DS2 genes is highly dehydration-specific in potato leaves, is not inducible by
      cold, heat, salt, hypoxia or oxidative stresses, and is independent of abscisic
      acid (ABA). Now it is shown that StDS2 does not respond either to sucrose or any
      plant hormones. Conservation of DS2 genes with this unique mode of regulation was
      studied in the solanaceous species with different relationships to potatoes. DS2
      orthologues were identified by DNA sequence alignment in the closely related
      Lycopersicon and Capsicum species but not in the more distantly related Nicotiana
      sp. DNA and RNA gel blot analysis revealed the presence of a gene highly
      homologous to the potato gene StDS2 in tomato (LeDS2) with the same desiccation
      specific expression in leaves and organ-specific expression in flowers and green
      fruits. The LeDS2 promoter was isolated and found to be almost identical in
      sequence with the promoter of StDS2, except for a 45-bp insertion in tomato. In
      contrast, no gene highly similar to StDS2 was detected in Nicotiana species on
      DNA gel blots. Neither StDS2 nor LeDS2 promoter regions were able to confer
      expression for the beta-glucuronidase (GUS) reporter gene in transgenic tobacco
      plants indicating that the trans regulatory factors necessary for DS2 expression
      are not conserved either in Nicotiana tabacum. These data suggest a narrow
      species-specificity and late evolution of the DS2-type genes within the family
      Solanaceae.

PMID- 15854836
TI  - The cellulose/lignin assembly assessed by molecular modeling. Part 2: Seeking for
      evidence of organization of lignin molecules at the interface with cellulose.
AB  - We have extended our previous computational investigation of the cellulose lignin
      assembly by considering more complex systems. Surface coverage of cellulose,
      structural parameters such as molecular mass and structural features of the
      lignin models and the presence of an explicit hydrated environment have been
      taken into account to examine their influence on the associative interactions
      between cellulose and lignin. To this end, different lignin molecular models,
      from beta-O-4 dimers up to a 20-units oligomer, were considered. Independently of
      the system studied, the key feature of the adsorption is globally preserved:
      aromatic rings of lignin adopt a preferential parallel orientation relative to
      the cellulose surface. Such structural order appears to be limited to the first
      shell of lignin units adsorbed on the cellulose. The pre-organization of the
      lignin monolayer at the surface of cellulose is not significantly changed at the
      interface with water. However, adsorption significantly depends on the molecular
      mass and the structure of lignin. The structural order is significantly hindered
      by the presence of branching or some particular inter-units linkages in the
      structure of lignin. Such results rationalize the apparent contradiction between
      the available experimental results.

PMID- 15854837
TI  - Two plasma membrane H(+)-ATPase genes are differentially expressed in iron
      deficient cucumber plants.
AB  - Aim of the present work was to investigate the involvement of plasma membrane
      (PM) H(+)-ATPase (E.C. 3.6.3.6) isoforms of cucumber (Cucumis sativus L.) in the
      response to Fe deficiency. Two PM H(+)-ATPase cDNAs (CsHA1 and CsHA2) were
      isolated from cucumber and their expression analysed as a function of Fe
      nutritional status. Semi-quantitative reverse transcriptase (RT)-PCR and
      quantitative real-time RT-PCR revealed in Fe-deficient roots an enhanced
      accumulation of CsHA1 gene transcripts, which were hardly detectable in leaves.
      Supply of iron to deficient plants caused a decrease in the transcript level of
      CsHA1. In contrast, CsHA2 transcripts, detected both in roots and leaves,
      appeared to be unaffected by Fe. This work shows for the first time that a
      transcriptional regulation of PM H(+)-ATPase involving a specific isoform occurs
      in the response to Fe deficiency.

PMID- 15854838
TI  - The effect of growth regulators and sucrose on anthocyanin production in
      Camptotheca acuminata cell cultures.
AB  - The effect of different concentrations of growth regulators and sucrose on
      anthocyanin production in cell suspension cultures of Camptotheca acuminata
      Decaisne (Nyssaceae) was described for the first time and qualitatively and
      quantitatively evaluated. Anthocyanin production was significantly greater in the
      presence of kinetin, compared to benzyladenine, with the greatest concentration
      observed in the presence of 2 microM kinetin. No significant differences in
      anthocyanin production were observed when comparing 2,4-dichlorophenoxyacetic
      acid to alpha-naphthaleneacetic acid, except when using 2 microM, 2,4
      dichlorophenoxyacetic acid, which resulted in greater anthocyanin production.
      High sucrose concentration enhanced the production of anthocyanins. Based on the
      absence of anthocyanin production in the dark, we concluded that light was
      essential for stimulating anthocyanin production. The optimised medium consisted
      of: 2 microM kinetin, 2 microM 2,4-dichlorophenoxyacetic acid and 292 mM sucrose.
      HPLC/DAD and HPLC/MS analyses revealed that the main anthocyanin was Cy 3-O
      galactoside and that the minor derivative was Cy 3-O-glucoside.

PMID- 15854839
TI  - The cellulose/lignin assembly assessed by molecular modeling. Part 1: adsorption
      of a threo guaiacyl beta-O-4 dimer onto a Ibeta cellulose whisker.
AB  - The assembly of the two major cell wall components, cellulose and lignin, were
      investigated at the atomistic scale using molecular dynamics simulations. To this
      end, a molecular model of a cellulose crystal corresponding to the allomorph
      Ibeta and exhibiting different surfaces was considered to mimic the carbohydrate
      matrix present in native wood cell wall. The lignin model compound considered
      here is a threo guaiacyl beta-O-4 dimer. The dynamical process of adsorption of
      the lignin dimer onto the different surfaces of the cellulose crystal was
      examined. The modes of association between the two constituents were analyzed;
      energies of adsorption of the dimer are calculated favorable and of the same
      order of magnitude on all sides of the cellulosic model, suggesting that the
      deposition of lignin precursors onto cellulose fibers is non-specific from an
      enthalpic point of view. Interestingly, geometrical characteristics and
      energetical details of the adsorption are surface-dependent. Computed data have
      underlined the predominant contribution of van der Waals interactions for
      adsorption onto the (200) face, as well as the major influence of H-bonding
      interactions in the dynamical process of adsorption onto (110) and (1-10) faces.
      A large number of adsorption sites have been identified and a noticeable "flat"
      geometry of adsorption of the lignin dimer has been observed, as a consequence of
      the stacking interactions between lignin aromatic rings and C-H groups of
      cellulose. Importantly, these dispersive interactions lead to a preferential
      parallel orientation of lignin aromatic rings relative to the cellulose surface,
      notably on the (200) face. Such a parallel orientation is consistent with
      previously reported experimental observations.

PMID- 15854840
TI  - Luminosity and contrast normalization in retinal images.
AB  - Retinal images are routinely acquired and assessed to provide diagnostic evidence
      for many important diseases, e.g. diabetes or hypertension. Because of the
      acquisition process, very often these images are non-uniformly illuminated and
      exhibit local luminosity and contrast variability. This problem may seriously
      affect the diagnostic process and its outcome, especially if an automatic
      computer-based procedure is used to derive diagnostic parameters. We propose here
      a new method to normalize luminosity and contrast in retinal images, both intra-
      and inter-image. The method is based on the estimation of the luminosity and
      contrast variability in the background part of the image and the subsequent
      compensation of this variability in the whole image. The application of this
      method on 33 fundus images showed an average 19% (max. 45%) reduction of
      luminosity variability and an average 34% (max. 85%) increment of image contrast,
      with a remarkable improvement, e.g., over low-pass correction. The proposed image
      normalization technique will definitely improve automatic fundus images analysis
      but will also be very useful to eye specialists in their visual examination of
      retinal images.

PMID- 15854841
TI  - 3D multi-scale vessel enhancement filtering based on curvature measurements:
      application to time-of-flight MRA.
AB  - In this paper we evaluate the use of voxel intensity curvature measurements to
      enhance vessels in 3D MRA images. We compare a multi-scale discrete kernel filter
      (MaxCurve) to the Hessian matrix based filter proposed by Frangi and co-workers.
      The MaxCurve filter is based on the maximum difference between the negative
      curvature computed along orthogonal lines defined by a 3x3x3 kernel. Filter
      performance is assessed using measures of vessel and background separation
      (contrast and the area under the ROC curve). Filter parameters are optimized
      using a training set of four typical time-of-flight MRA images and tested on a
      separate set of ten MRA images with the same acquisition parameters. The filters
      tended to provide good MIP image contrast enhancement. The filters are applied to
      MRA images acquired with different parameters and field strengths indicating
      potential usefulness for a variety of images. Overall the discrete kernel and
      Hessian matrix filter performed quite similarly.

PMID- 15854842
TI  - Flux driven automatic centerline extraction.
AB  - We present a fast, robust and automatic method for computing centerline paths
      through tubular structures for application to virtual endoscopy. The key idea is
      to utilize a skeletonization algorithm which exploits properties of the average
      outward flux of the gradient vector field of a Euclidean distance function from
      the boundary of the structure. The algorithm is modified to yield a collection of
      3D curves, each of which is locally centered. The approach requires no user
      interaction, is virtually parameter free and has low computational complexity. We
      validate the method quantitatively on a number of synthetic data sets with known
      centerlines and qualitatively on colon and vessel data segmented from CT and CRA
      images.

PMID- 15854843
TI  - White matter fiber tract segmentation in DT-MRI using geometric flows.
AB  - In this paper, we present a 3D geometric flow designed to segment the main core
      of fiber tracts in diffusion tensor magnetic resonance images. The fundamental
      assumption of our fiber segmentation technique is that adjacent voxels in a tract
      have similar properties of diffusion. The fiber segmentation is carried out with
      a front propagation algorithm constructed to fill the whole fiber tract. The
      front is a 3D surface that evolves with a propagation speed proportional to a
      measure indicating the similarity of diffusion between the tensors lying on the
      surface and their neighbors in the direction of propagation. We use a level set
      implementation to assure a stable and accurate evolution of the surface and to
      handle changes of topology of the surface during the evolution process. The fiber
      tract segmentation method does not need a regularized tensor field since the
      surface is automatically smoothed as it propagates. The smoothing is done by an
      intrinsic surface force, based on the minimal principal curvature. This
      segmentation can be used for obtaining quantitative measures of the diffusion in
      the fiber tracts and it can also be used for white matter registration and for
      surgical planning.

PMID- 15854844
TI  - Thoracic non-rigid registration combining self-organizing maps and radial basis
      functions.
AB  - An automatic three-dimensional non-rigid registration scheme is proposed in this
      paper and applied to thoracic computed tomography (CT) data of patients with
      stage III non-small cell lung cancer (NSCLC). According to the registration
      scheme, initially anatomical set of points such as the vertebral spine, the ribs,
      and shoulder blades are automatically segmented slice by slice from the two CT
      scans of the same patient in order to serve as interpolant points. Based on these
      extracted features, a rigid-body transformation is then applied to provide a pre
      registration of the data. To establish correspondence between the feature points,
      the novel application of the self-organizing maps (SOMs) is adopted. In
      particular, the automatic correspondence of the interpolant points is based on
      the initialization of the Kohonen neural network model capable to identify 500
      corresponding pairs of points approximately in the two CT sets. Then, radial
      basis functions (RBFs) using the shifted log function is subsequently employed
      for elastic warping of the image volume, using the correspondence between the
      interpolant points, as obtained in the previous phase. Quantitative and
      qualitative results are also presented to validate the performance of the
      proposed elastic registration scheme resulting in an alignment error of 6 mm, on
      average, over 15 CT paired datasets. Finally, changes of the tumor volume in
      respect to each reference dataset are estimated for all patients, which indicate
      inspiration and/or movement of the patient during acquisition of the data. Thus,
      the practical implementation of this scheme could provide estimations of lung
      tumor volumes during radiotherapy treatment planning.

PMID- 15854845
TI  - Real-time synthesis of bleeding for virtual hysteroscopy.
AB  - In this paper we present a method for simulating bleeding in a virtual reality
      hysteroscopic simulator for surgical training. The simulated bleeding is required
      to be visually appealing while at the same time instantaneously responsive to any
      feedback that the surgeon may be conducing to the virtual environment. In order
      to meet these real-time requirements, we have based the simulation on graphical
      fluid solvers. These solvers primarily work best over a 2D domain. For correct
      visualization in the hysteroscopic simulator, it is, however, necessary to
      perform the simulation fully in 3D. Therefore in this paper we also present the
      design modifications for 3D graphical fluid solving and show how to use
      parallelization to maintain real-time behavior. We also discuss how the
      incorporation of massless particles into the simulation can improve the visual
      quality of the results by limiting numerical dissipation effects.

PMID- 15854846
TI  - Radiographic stereometry for non-metal-backed acetubular cups: 3D wear estimation
      and related uncertainty.
AB  - The aim of this work was to assess the 3D wear of non-metal-backed acetubular
      cups from two conventional digitized radiographs. The centers of the femoral head
      and the metal ring in the equatorial plane of the cup are located using 3D pose
      techniques for spheres and circles from sampled points in the images. The method
      used to locate these points of interest and also estimate their covariance is
      fully described in previous work. The covariance is used to decrease the bias of
      the pose estimation, while bootstrapping decreases its variance and gives access
      to the directions of minimal variability between the two centers for each image.
      These directions are used to produce the final distance after reconstruction.
      Results are compared with the 2D technique working on a single anteroposterior
      (AP) radiograph and assuming null lateral wear. Validation is performed on
      acetubular cups: (a) simulated by Monte-Carlo, (b) implanted on a pelvic model,
      and (c) acquired on patients just after arthroplasty. The accuracy in wear for
      simulation increases from about one to four hundredths of a millimeter as caudal
      and cranial absolute angulations decreases from 45 degrees to 30 degrees . It is
      more difficult to assess for real prostheses, but results are shown to lie within
      the manufacturer's dimensional tolerances. Globally, the access to the lateral
      wear is obtained at the expense of confidence in the global linear wear (0.06
      mm), which is doubled with regard to 2D technique but still satisfying for
      clinical use, whereas the bias of the measurement is decreased.

PMID- 15854847
TI  - Assimilating intraoperative data with brain shift modeling using the adjoint
      equations.
AB  - Biomechanical models of brain deformation are increasingly being used to
      nonrigidly register preoperative MR (pMR) images of the brain to the surgical
      scene. These model estimates can potentially be improved by incorporating sparse
      displacement data available in the operating room (OR), but integrating the
      intraoperative information with model calculations is a nontrivial problem. We
      present an inverse method to estimate the unknown boundary and volumetric forces
      necessary to achieve a least-squares fit between the model and the data that is
      formulated in terms of the adjoint equations, which are solved directly by the
      method of representers. The scheme is illustrated in a 2D simulation and in a 2D
      approximation based on a patient case using actual OR data.

PMID- 15854848
TI  - HD-16: a new quality of life instrument specifically designed for insomnia.
AB  - BACKGROUND AND PURPOSE: To design a new quality of life (QoL) instrument
      specifically for insomnia. PATIENTS AND METHODS: Based on severe insomniacs'
      interviews, we have built a new quality of life scale that has been tested in one
      group of 240 severe insomniacs, in one group of 422 mild insomniacs and in one
      group of 391 good sleepers. Ten steps led to the construction of a specific QoL
      scale. RESULTS: Five dimensions have been validated as both relevant and
      independent from each other. Sixteen items out of the 43 initially tested were
      retained and significantly different within the groups in each dimension. Based
      on the 16 items selected, we called the scale Hotel Dieu 16 (HD-16). We have
      therefore verified the score's specificity (correlation score of +0.36) and the
      reliability of the scale (Cronbach coefficient alpha=0.78). CONCLUSION: HD-16 may
      be used as a focused instrument to better assess an insomniac's quality of life.

PMID- 15854849
TI  - The pulse transit time arousal index in obstructive sleep apnea before and after
      CPAP.
AB  - BACKGROUND AND PURPOSE: Pulse transit time (PTT) is a non-invasive index which
      reflects changes in peripheral vascular resistance and intrathoracic pressure.
      PTT arousal index (PTT Ar/I) is defined as the frequency (number/hour) of a
      defined decrease in PTT which may serve as a marker for respiratory events, and
      associated arousals which occur in patients with obstructive sleep apnea (OSA).
      This study was designed to evaluate the PTT Ar/I before and after patients with
      OSA were treated with continuous positive airway pressure (CPAP). PATIENTS AND
      METHODS: Individuals referred for evaluation of possible OSA underwent split
      night polysomnography (PSG). The findings from 144 consecutive patients with a
      respiratory disturbance index (RDI)>/=20, who demonstrated at least a 50% drop in
      RDI with CPAP, provide the basis for this analysis. The PTT Ar/I measured before
      and after CPAP were compared to other measures of severity for OSA, including RDI
      and arousal index. RESULTS: The PTT Ar/I correlates with the RDI (r=0.43,
      P</=0.0001) and with the arousal index (r=0.43, P<0.0001). Moreover, the decrease
      in RDI and arousal index that occurs with CPAP treatment correlates with a
      similar decrease in the PTT Ar/I (r=0.54, P<0.0001). CONCLUSIONS: The PTT Ar/I
      correlates well with other standard measures of severity in patients with OSA and
      is potentially a non-invasive marker with which to measure the frequency of
      disruptive events that occur during sleep.

PMID- 15854850
TI  - Awake flow limitation with negative expiratory pressure in sleep disordered
      breathing.
AB  - BACKGROUND AND PURPOSE: Although upper airway collapsibility (UAC) is
      theoretically useful to anticipate severity of sleep-disordered breathing (SDB),
      inspiratory UAC measurements are poorly correlated with obstructive sleep apnea
      (OSA) severity. PATIENTS AND METHODS: We investigated in 15 healthy and 35 SDB
      awake subjects whether negative expiratory pressure (NEP) could be a technique
      which would allow us to anticipate SDB severity. We characterized in these
      subjects, both in supine and sitting position, at -5 and -10 cm H(2)O, the flow
      volume curves and a new NEP quantitative index (ratio of the 'areas under the
      curve' of NEP flow-volume loop vs. spontaneous flow-volume loop). RESULTS:
      Abnormal flow-volume curves were significantly more frequent in patients with SDB
      than in healthy subjects, for both negative pressures in sitting posture and -10
      cm H(2)O in supine position. The quantitative index decreased with the severity
      of SDB, independently of confounding factors (age, body mass index (BMI) and
      expiratory reserve volume (ERV)). In the supine position, at -5 and -10 cm H(2)O,
      thresholds of less than 160 and 180% respectively identified in 96.6% of SDB,
      whereas thresholds of greater than 160 and 180% were adequately classified in
      76.9% of controls. CONCLUSIONS: NEP flow-volume curves and quantitative index
      during wakefulness are useful methods to detect UAC. These results, however,
      should be confirmed by a prospective study in the general population.

PMID- 15854851
TI  - Modified thoracic impedance plethysmography to monitor sleep apnea syndromes.
AB  - BACKGROUND AND PURPOSE: In order to identify sleep disorders by thoracic
      impedance plethysmography (TIP), we propose several new techniques: the
      application of an adaptive filter, a scaled Fourier linear combiner (SFLC) to
      eliminate cardiac-derived fluctuation in the impedance waveform, and the use of
      heart rate variability (HRV) to ascertain whether the airflow is obstructed.
      PATIENTS AND METHODS: Laboratory simulation experiments on four healthy
      individuals and actual overnight measurements on five patients with sleep
      disorders were carried out. Amplified thoracic impedance change (DeltaZ), ECG, a
      phonocardiograph, a pneumotachograph and a standard polysomnograph were recorded.
      The SFLC was applied to DeltaZ to selectively extract the cardiac-synchronous
      component (DeltaZ(CSC)), and the remainder of the waveform (DeltaZ(REM)) was low
      pass filtered to estimate the waveform driven by respiration. The HRV was divided
      into respiratory synchronous (HRV(R)) and low frequency (HRV(L)) components.
      RESULTS: The SFLC could drastically extract DeltaZ(CSC) from DeltaZ and thereby
      demonstrate a DeltaZ(REM) pattern quite similar to the flow-volume curve of the
      pneumotachograph. Central sleep apnea could be identified as the cessation of
      DeltaZ(REM) and concomitant attenuation of HRV(R). Obstructive sleep apnea could
      be identified as the maintenance of rhythmic but attenuated variations of
      DeltaZ(REM) accompanied by asynchronous fluctuation of HRV(R) against
      DeltaZ(REM). Central hypopnea could be identified as a normal but attenuated
      waveform in both DeltaZ(REM) and HRV(R). A large fluctuation in HRV(L) was
      observed during repetitive appearances of apnea/hypopnea in the nocturnal
      experiments. CONCLUSION: The modified TIP together with HRV provides a superior
      tool for accurate and convenient definition of sleep apnea syndromes.

PMID- 15854852
TI  - Periodic limb movements and sleepiness in obstructive sleep apnea patients.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to assess the possibility that
      periodic limb movements during sleep (PLMS) could play an additive role in the
      sleepiness associated with obstructive sleep apnea syndrome (OSAS) before
      treatment, or could account for residual sleepiness in successfully CPAP-treated
      patients. PATIENTS AND METHODS: In order to test this hypothesis, we compared
      objective sleepiness, assessed by the Multiple Sleep Latency Test (MSLT) and
      subjective sleep propensity, assessed by the Epworth Sleepiness Scale (ESS), in a
      clinical series of 57 patients consecutively diagnosed with OSAS (apnea/hypopnea
      index, 53.3+/-26.15), before and after 1 year of treatment with CPAP. RESULTS:
      Twenty-two patients (38.5%) had significant PLMS (at least 5 PLMS/h of sleep;
      mean 52.9+/-53.9) in absence of apneas (with CPAP). The two groups (with and
      without PLMS) were similar in gender distribution, BMI, apnea/hypopnea index or
      CPAP level. Patients with PLMS were older than those without PLMS. Sleepiness
      measurements following OSAS diagnosis and after 1 year of CPAP treatment were
      similar in patients PLMS compared to those without significant PLMS. There was no
      correlation in the PLMS patient group between the PLM index, Epworth Sleepiness
      Scale score and mean latency in the MSLT. CONCLUSION: In this study we did not
      find a link between PLMS and increased objective or self-evaluated sleepiness in
      OSAS patients, before or after treatment with CPAP.

PMID- 15854853
TI  - Electroencephalography and subjective ratings of sleep deprivation.
AB  - BACKGROUND AND PURPOSE: Sleep-related vehicle accidents account for many injuries
      and fatalities each year on monotonous motorways and roads. To effectively
      prevent such incidents requires greater knowledge of the mechanisms and
      development of the effects of sleep deprivation. Ten volunteers participated in a
      laboratory study aimed to analyze the way changes in wakefulness were described
      in terms of EEG changes and subjective ratings. PATIENTS AND METHODS: For each
      subject, the study consisted of four testing sessions that varied in length on
      different days: one session each of 60, 90, and 120 min when sleep-deprived, and
      one session of 120 min when rested. Changes in wakefulness were analyzed using
      electroencephalographic recordings and ratings on two different scales, the
      Karolinska Sleepiness Scale (KSS) and the Category-Ratio Scale (CR-10). RESULTS:
      The results indicate quite conclusively that significant changes in the
      perception of sleepiness occur during the first 60-90 min of sedentary,
      monotonous work. Beyond this time period, subjective and physiological changes
      remained constant throughout the rest of the 120-min period. CONCLUSION: In
      general, the subjective rating scales highly and significantly correlated with
      theta activity in both tired and rested states and with alpha activity in the
      rested state. Similar results were seen using both subjective rating scales.

PMID- 15854854
TI  - Structural cardiac changes as a predictor of respiratory complications after
      adenotonsillectomy for obstructive breathing during sleep in children.
AB  - BACKGROUND AND PURPOSE: To determine the association between structural cardiac
      changes and postoperative respiratory complications after adenotonsillectomy for
      obstructive breathing during sleep. PATIENTS AND METHODS: Forty-eight children,
      ages 2-18 years, undergoing adenotonsillectomy for obstructive breathing during
      sleep were recruited for this case control study. The case group consisted of 24
      children with postoperative respiratory complications after adenotonsillectomy
      who also had an echocardiogram. An equal number of children without postoperative
      respiratory complications after adenotonsillectomy were recruited as controls.
      Left ventricular mass (LVM) was calculated from 2D guided M mode
      echocardiographic measurements of the left ventricle. Left ventricular mass index
      (LVMI) was calculated as left ventricular mass/height(2.7). Left ventricular
      hypertrophy (LVH) was defined as LVMI index greater than the 95th percentile for
      age. The two groups were compared for demographic variables and cardiac
      structure. RESULTS: The two groups did not significantly differ by age, height,
      gender or racial distribution. LVH and right ventricular (RV) dimension greater
      than the 95th percentile for age remained significantly associated with the
      occurrence of postoperative respiratory complications after controlling for body
      mass index (BMI) Z score, age, gender, race, systolic and diastolic blood
      pressure. CONCLUSIONS: The increased prevalence of structural cardiac changes in
      the group with complications (P<0.01) suggests an underlying cardiac origin for
      postoperative respiratory complications in this group of children.

PMID- 15854855
TI  - Sleep duration and caffeine consumption in a French middle-aged working
      population.
AB  - OBJECTIVE/BACKGROUND: To explore the association between sleep duration and daily
      caffeine intake in a working population. Caffeine acutely disrupts sleep in the
      laboratory, but the inter-relations between sleep and caffeine intake in daily
      life are ill-known. METHODS: Questionnaire and diary based survey of 1498 persons
      from the GAZEL cohort of employees of the National Electricity and Gas Company
      (EDF-GDF) working in various locations in the Paris and South-West France areas.
      We analyzed total sleep time, our primary measure, and time in bed, both by sleep
      logs. We assessed daily intake of caffeine, consumption of alcohol and tobacco,
      use of hypnotics, and daytime somnolence, all by questionnaire. RESULTS: Multiple
      linear regression analysis did not find a significant relationship between total
      sleep time and daily caffeine intake less than 8 cups of coffee per day, after
      controlling for age, gender, alcohol intake, smoking status, and use of
      hypnotics. By contrast, time in bed was reduced as caffeine intake increased
      (beta=-0.125; P<0.001). Higher caffeine intake was not related to a higher
      daytime somnolence. CONCLUSION: Despite the well-known acute effects of caffeine
      on sleep, habitual use of up to 7 cups of coffee (or 600 mg of caffeine
      equivalent) per day was not associated with decreased duration of sleep.

PMID- 15854856
TI  - The association between narcolepsy and REM behavior disorder (RBD).
AB  - BACKGROUND AND PURPOSE: Rapid eye movement (REM) sleep Behavior Disorder (RBD) is
      a movement disorder associated with loss of REM-related muscle atonia and is
      characterized by complex, vigorous and frequently violent dream-enacting behavior
      during REM sleep. RBD is usually idiopathic or secondary to neurological problems
      such as Parkinson's disease. This study looked at the association of RBD with
      another sleep disorder, narcolepsy. PATIENTS AND METHODS: Seventy-eight
      questionnaires were sent to known narcoleptics chosen at random from those with
      contact details available at the center. The questionnaire addressed current
      narcolepsy symptoms, medication use and symptoms of RBD. Positive questionnaire
      results were followed up with a telephone interview. Limited polysomnography
      (PSG) data was also analyzed. RESULTS: Fifty-five patients responded (response
      rate 71%). Of these, 20 (36%) had symptoms suggestive of RBD. The typical RBD
      patient is an older male (mean age of onset 60.9 years, 87% male); however, in
      this study, females were as likely to have RBD as males, and the mean age was 41
      years. Sixty-eight percent of patients who regularly experienced cataplexy and
      the associated symptoms of narcolepsy (sleep paralysis, hypnogogic hallucinations
      and automatic behavior) had RBD, compared to 14% of those who never or rarely
      experienced these symptoms. CONCLUSION: This study implies a stronger
      relationship between these disorders than a previously published figure of 7-12%
      This is clinically significant as RBD is a potentially distressing but readily
      treatable disorder. It follows that narcoleptics, especially those with cataplexy
      and other associated symptoms, should be questioned about symptoms of RBD and
      treated accordingly. Similarly, anyone presenting with RBD should be assessed for
      symptoms of narcolepsy, particularly if female or of a younger age group than
      would otherwise be expected.

PMID- 15854857
TI  - Night-to-night variability in periodic leg movements in patients with restless
      legs syndrome.
AB  - BACKGROUND AND PURPOSE: Although a night-to-night variability in periodic leg
      movements (PLM) occurrence has been described in patients with primary PLM
      disorder and sleep apnea syndrome, no study has apparently considered the inter
      night effect on PLM index during wakefulness and sleep in patients with Restless
      Legs Syndrome (RLS). Moreover, no study has examined the night-to-night
      variability in PLM index according to sleep stage and time of night. We therefore
      examined changes in PLM index during wakefulness and sleep during two consecutive
      nights in a group of untreated RLS patients. PATIENTS AND METHODS: Twenty-eight
      drug-free RLS patients, aged 53.4+/-2.3 yr, with a mean International Restless
      Legs Syndrome Study Group (IRLSSG) severity score of 20.2+/-1.6, were studied
      during two consecutive nights. PLM duration and interval, PLM index during
      wakefulness (PLMWI), during total sleep time (PLMSI), as well as during each
      sleep stage were measured. Analysis was also extended to examine PLM occurrence
      during sleep cycles. RESULTS: In the group of patients as a whole, the PLMW and
      PLMS index, duration and interval did not show significant difference between
      nights, these measures being consistently similar for both nights. Comparison of
      PLMS index between different sleep stages did not reveal inter-night differences.
      Nocturnal variation in PLM number, duration and interval for total recording time
      and sleep period revealed a progressive decline across the night for PLM index
      (P</=0.0001) but no interaction, the changes being similar in first and second
      nights. However, a large intra-individual variability was present with a
      correlation coefficient between nights of 0.60 for the PLMWI (P=0.001) and 0.54
      (P=0.003) for the PLMSI. The individual inter-night changes in PLM index were
      independent of age, IRLSSG severity score, duration of the disease and changes in
      sleep parameters. CONCLUSIONS: This study shows that the index and the nocturnal
      pattern of PLM occurrence are highly reliable across nights in RLS patients,
      suggesting that a single-night study may be sufficiently sensitive to confirm
      diagnosis and associated sleep disturbances in these patients. However, an
      individual inter-night variability is present, independent of age, severity and
      duration of the disease, which should be considered in the clinical evaluation.

PMID- 15854858
TI  - Sleep quality and more common sleep-related problems in medical students.
AB  - BACKGROUND AND PURPOSE: The aim of this paper is to conduct a survey based on a
      questionnaire that would characterize nighttime and daytime habits in medical
      students; to estimate how subjective sleep quality is associated with nighttime
      and daytime habits and sleep problems in students; to estimate how academic
      progress and workload is associated with subjective sleep quality, nighttime and
      daytime habits and sleep problems in students; and to estimate the prevalence of
      self-reported sleep problems in Estonian medical students. PATIENTS AND METHODS:
      The study group included 413 medical students of the University of Tartu, aged 19
      33 years. The self-reported Sleep and Daytime Habits Questionnaire (S&DHQ)
      covered demographic characteristics (4 questions) and sleep and daytime habits
      (24 questions). Of the latter, 18 multiple-choice questions provided answers
      expressed as discontinuous variables on a nominal scale, 4 questions provided
      answers expressed as continuous variables on an interval scale, and 2 questions
      provided answers expressed as quality characterization on a five-point scale. The
      supplement includes information about lifestyle and academic progress on a four
      point scale. RESULTS: The S & DHQ could be used to study sleep problems in young
      medical students. The subjective sleep quality of students was as follows:
      excellent-29%; good-40%; satisfactory-24%; poor 6%; very poor-1%. Sleep quality
      is associated with academic progress (R=0.174; P<0.001), leisure activity
      (R=0.210; P<0.001), and living conditions (R=0.195; P<0.001). Sleep quality is
      not associated with students' daily (R=0.021; P>0.05) or nightly workload
      (R=0.0664; P>0.05). Daytime sleepiness poses a significant problem for students
      and is associated both with sleep disorders and work while studying. CONCLUSIONS:
      The study demonstrates that complaints about sleep problems are common in young
      medical students.

PMID- 15854860
TI  - Iron deficiency with normal ferritin levels in restless legs syndrome.
AB  - This report describes a patient with iron deficiency in bone marrow examination
      and iron-responsive restless legs syndrome (RLS), in whom serum ferritin levels
      were well above the conventional cutoff for considering iron deficiency. The
      predictive value of serum ferritin for iron deficiency in RLS depends on the
      cutoff employed, on the pre-test likelihood of iron deficiency and on coexisting
      inflammatory conditions. Bone marrow examination is helpful when ferritin levels
      are equivocal.

PMID- 15854859
TI  - Analysis of the first night effect and sleep parameters in medically refractory
      epilepsy patients.
AB  - OBJECTIVES: To assess the first night effect (FNE) and compare sleep stage
      proportions to normative values in a sample of medically refractory epilepsy
      patients. PATIENTS AND METHODS: Sleep parameters of 53 epilepsy patients, ages
      (18-56, mean: 34+/-12, 25 females 28 men), who underwent two consecutive nights
      of polysomnography (PSG) were compared. Non-rapid eye movement (NREM) stage 3 and
      NREM stage 4 were combined as slow wave sleep (SWS). Sleep efficiency, sleep
      latency, rapid eye movement (REM) latency, number of stage shifts, total minutes
      and proportion of total sleep time for stage 1, stage 2, SWS, and REM sleep were
      compared between the 2 nights. RESULTS: SWS was the only parameter that differed
      between nights 1 and 2 for both total minutes (P=0.02) and proportion of total
      sleep time (P=0.01), although the means for both nights were within the normative
      range. Comparing sleep proportions to normative values indicates that our
      patients had increased NREM stage 1 and decreased REM sleep. CONCLUSIONS: We
      observed a minimal FNE in this sample of epilepsy patients manifested by reduced
      SWS. Multiple PSGs to accommodate the FNE may not be necessary in this
      population.

PMID- 15854861
TI  - Restless legs syndrome associated with primary hyperparathyroidism.
AB  - Restless legs syndrome (RLS) is a poorly understood sleep-related movement
      disorder which can be primary or associated with other conditions, most commonly
      iron deficiency, uremia and peripheral nerve disease. We present a case of RLS
      with an unusual secondary cause: primary hyperparathyroidism with hypercalcemia.
      This patient experienced complete and sustained relief of RLS symptoms
      immediately after parathyroidectomy, with normalization of her serum parathyroid
      hormone (PTH) and calcium levels. Early recognition and treatment of this
      uncommonly detected underlying cause is important because it is potentially
      curative in this frequently disabling condition for which usually only
      symptomatic treatment is available.

PMID- 15854863
TI  - Apnea while awake.

PMID- 15854864
TI  - Body image, eating behaviors, and attitudes toward exercise among gay and
      straight men.
AB  - Gay men tend to be more dissatisfied with their bodies and may be at greater risk
      for symptoms of eating disorders compared to heterosexual men. However, the
      majority of research conducted with gay and heterosexual men has implemented
      instruments designed to assess eating disorder symptomatology in women. The
      present study assessed differences between gay and heterosexual men using the
      Male Eating Behavior and Body Image Evaluation (MEBBIE), an instrument designed
      to assess attitudes and behaviors related to eating, exercise and body image
      specifically in men. Analyses of MEBBIE scale means with body mass index (BMI) as
      the covariate indicated that, relative to their heterosexual counterparts, gay
      men diet more, are more fearful of becoming fat, and are more dissatisfied with
      their bodies in general as well as with their degree of muscularity. Gay men were
      also more likely than heterosexual men to hold distorted cognitions about the
      importance of having an ideal physique. Contrary to hypotheses, however, gay and
      straight men did not differ in the degree to which they exercised or felt guilty
      about missing a workout. Results are discussed in light of previous findings, and
      implications for clinical practice and future research are considered.

PMID- 15854866
TI  - Dispositional correlates of addictive behaviors in college women: binge eating
      and heavy drinking.
AB  - Binge eating and alcohol abuse are often conceptualized as addictive behaviors.
      As these behaviors are relatively common among undergraduate college women, we
      examined whether common dispositional variables underlie their occurrence. Three
      hundred and thirty-five undergraduate women completed self-report questionnaires
      about their eating and alcohol use habits as well as dispositional measures of
      impulsivity, tolerance of deviance, self-esteem, rejection sensitivity,
      extraversion-introversion, conscientiousness, and emotional stability. Multiple
      regression analyses showed that women who either binge eat or abuse alcohol, but
      not both, have similar dispositional characteristics. Both groups exhibited a
      high degree of impulsivity and endorsed socially deviant attitudes; thus, both
      groups could be viewed as "externalizers." In contrast, women who admitted to
      both addictive behaviors, i.e., binge eating as well as alcohol abuse, were not
      particularly impulsive or socially deviant, but manifested a high degree of
      emotional instability ("neuroticism"); thus, these women might be considered
      "internalizers." The theoretical and clinical implications of these findings are
      discussed.

PMID- 15854865
TI  - Binge eating among African American and Caucasian bariatric surgery candidates.
AB  - Bariatric surgery is an increasingly utilized treatment for severe obesity,
      especially among women. Although African American women have high rates of severe
      obesity, most research investigating psychological correlates of obesity has been
      conducted with Caucasians. This study examined the characteristics of African
      American women seeking bariatric surgery, and ethnic differences in BED rates and
      correlates of binge eating. Finally, we examined whether the association between
      psychological factors associated with binge eating was moderated by ethnicity.
      Results indicated that African American women had higher BMIs, higher self
      esteem, and less depression than Caucasians. There were no differences in rates
      of binge eating or BED. Both depression and self esteem accounted for unique
      variance in binge eating; however, these relationships were not moderated by
      ethnicity. These results further highlight African Americans' vulnerability to
      EDs, and suggest that depression and low self esteem are equally relevant to
      binge eating in African American and Caucasian women.

PMID- 15854867
TI  - The cognitive behavioural model for eating disorders: a direct evaluation in
      children and adolescents with obesity.
AB  - OBJECTIVE: The cognitive behavioural model of bulimia nervosa [Fairburn, C.G.,
      Cooper, Z., & Cooper, P.J. (1986). The clinical features and maintenance of
      bulimia nervosa. In K.D. Brownell, and J.P. Foreyt (Eds.), Handbook of eating
      disorders: physiology, psychology and treatment of obesity, anorexia and bulimia
      (pp. 389-404). New York: Basic Books.] provides the theoretical framework for
      cognitive behaviour therapy of Bulimia Nervosa. For a long time it was assumed
      that the model can also be used to understand the mechanism of binge eating among
      obese individuals. The present study aimed to test whether the specific
      hypotheses derived from the cognitive behavioural theory of bulimia nervosa are
      also valid for children and adolescents with obesity. METHOD: The prediction of
      the model was tested using structural equation modeling. Data were collected from
      196 children and adolescents. RESULTS: In line with the model, the results
      suggest that a lower self-esteem predicts concerns about eating, weight and
      shape, which in turn predict dietary restraint, which then further is predictive
      of binge eating. DISCUSSION: The findings suggest that the mechanisms specified
      in the model of bulimia nervosa is also operational among obese youngsters.

PMID- 15854868
TI  - Subjective self-control and behavioural impulsivity coexist in anorexia nervosa.
AB  - OBJECTIVE: Anorexia nervosa (AN) has been associated with impulse regulation
      problems. This study investigated subjective and behavioural impulsivity in women
      with anorexia nervosa (n=15) and a control group (n=16). METHOD: A self-report
      measure (the impulsiveness, venturesomeness, and empathy questionnaire; I(7)) and
      two behavioural measures (a continuous performance task [CPT]; and a novel risk
      taking measure [Bets 16]) of impulsivity were used along with the Beck Depression
      Inventory (BDI). RESULTS: The AN group had elevated BDI scores and lower self
      reported impulsiveness and venturesomeness scores, but they also displayed
      impulsive behaviour on the CPT (more errors of commission with faster reaction
      times). DISCUSSION: The coexistence, in AN, of self-reported self-control and
      behavioural impulsivity indicates that the relationship between impulsivity and
      disordered eating in AN is more complex than previously recognised and supports
      the view that self-awareness in AN is low.

PMID- 15854869
TI  - Cognitive restraint is associated with higher intake of vegetables in a sample of
      university students.
AB  - The main objective of this study was to determine the association between
      cognitive restraint, nutritional intake and eating patterns in free-leaving
      subjects. We administered a questionnaire that included information about eating
      behaviour (restraint, disinhibition, and hunger), dietary intake, and physical
      activity; 380 students (60% female) completed the study. The association of
      restraint (low/high) and disinhibition (low/high) with dietary intake was tested
      using MANOVA in a 2x2 factorial design. Statistically significant main effects
      were further analyzed using ANOVAs. To identify eating patterns, factorial
      analysis was employed. Among women, high restrainers reported lower consumption
      of energy, pastry, and starchy foods, and higher consumption of vegetables, and
      fish, than low restrainers. In male subjects, high restrainers consumed
      significantly more vegetables than low restrainers. The major food pattern in
      female restrainers aggregate: higher consumption of legumes and fruit intake; and
      lower consumption of pastry, sugar, and starchy foods. In restrained men, the
      more important food pattern consists of vegetable soup, fruit, milk, and eggs.
      These differences should be considered in clinical interventions for individuals
      seeking a better body weight control.

PMID- 15854870
TI  - Psychometric properties of the Food Craving Inventory among obese patients with
      binge eating disorder.
AB  - OBJECTIVE: To examine the psychometric properties of the Food Craving Inventory
      [FCI; White, M. A., Whisenhunt, B. L., Williamson, D. A., Greenway, F. L., &
      Netemeyer, R. G. (2002). Development and validation of the food-craving
      inventory. Obesity Research, 10 (107-114)] in a group of obese patients with
      binge eating disorder (BED). METHOD: Participants were 122 obese patients seeking
      treatment for BED who completed the FCI. Data from the original 28-item FCI were
      examined. The current study sample was then compared to a community sample of
      obese patients. RESULTS: Confirmatory factor analysis confirmed the 4-factor
      structure of the FCI. An improved model was found following the deletion of 3
      items, yielding a 25-item questionnaire. Secondary analyses indicated differences
      in patterns of food cravings between BED patients and an obese comparison group.
      DISCUSSION: The current study confirmed the psychometric properties of the FCI
      for use with a group of treatment-seeking obese patients with BED. Collectively,
      the results imply that obese patients with BED may crave sweets to a heightened
      degree relative to other food classes.

PMID- 15854871
TI  - The influence of communicator weight on psychoeducational message acceptance in
      females with high vs. low levels of body image disturbance.
AB  - Researchers have yet to examine the effect of the communicator's weight status on
      participants' responses to an eating disorder or body dissatisfaction prevention
      program. It is plausible that participants may be reactive to the weight of the
      communicator (e.g., therapist), which might adversely affect acceptance of the
      message contained in the program. In the current study, 217 college females were
      randomly assigned to three communicator weight conditions (underweight, average
      weight, and overweight). Participants in each group were subdivided by trait body
      dissatisfaction level, based on a median split. The procedure involved the
      implementation of a well-established psychoeducational intervention designed to
      decrease endorsement of the thin-ideal. Results supported the overall efficacy of
      the intervention but indicated a minimal effect for participant's trait
      dissatisfaction level and communicator weight status on a variety of outcome
      measures. Limitations of the current study are provided, as well as
      recommendations for future research.

PMID- 15854872
TI  - Changing weight-loss expectations: a randomized pilot study.
AB  - Participants in weight-loss programs expect unreasonably large weight losses and
      believe that such reductions will produce dramatic improvements in their lives.
      The failure to achieve such benefits may contribute to poor maintenance of lost
      weight. This randomized pilot study investigated a new cognitive-behavioral
      intervention designed to modify unrealistic expectations regarding weight loss
      and its likely impact on appearance, attractiveness, and self-esteem. Twenty
      eight overweight and obese young women who completed 10 sessions of standard
      behavioral weight-loss treatment were randomly assigned to 10 additional sessions
      of either standard behavioral (SB) treatment or a reformulated cognitive
      behavioral (RCB) treatment. At posttreatment, the RCB intervention produced more
      realistic weight-loss expectations, decreased participants' motivation to lose
      weight as a means of improving self-confidence, and increased their overall self
      esteem, compared with the SB condition (all p's<.05). The mean posttreatment
      weight changes achieved in the SB (-6.2+/-4.5 kg) and RCB (-5.5+/-3.6 kg)
      conditions were equivalent, as were the amounts of weight regained during a 6
      month follow-up (SB=2.3+/-2.7 kg; RCB=1.5+/-1.7 kg). Collectively, these findings
      indicate that the RCB intervention was effective in changing unrealistic weight
      loss expectations, but it did not produce significantly better maintenance of
      lost weight than did the SB intervention.

PMID- 15854873
TI  - Stroop interference for food- and body-related words: a meta-analysis.
AB  - According to cognitive theories of eating disorders, biased information
      processing in favour of dysfunctional attitudes about food and body appearance
      plays a vital role in the development and maintenance of such disorders. Data
      from 27 studies evaluating Stroop interference for food- and body-related words
      with negative overtones were included in a meta-analysis in order to investigate
      whether such processing biases are specific to eating disordered samples.
      Participants were females characterised as eating disordered, non-eating
      disordered but nevertheless over-concerned with body appearance and eating, and
      normal controls. Mean Stroop interference for eating disordered females was of
      medium effect size (Cohen's d=0.48) and significantly larger than for both non
      eating disordered females concerned with body appearance and eating, and normal
      control females (both d=0.21). Stroop interference for eating disordered females
      was thus of fairly modest magnitude where it was unclear whether such
      interference is specific to this sample.

PMID- 15854874
TI  - Validation of a questionnaire measure of the relative reinforcing value of food.
AB  - The traditional method of measuring the relative reinforcing value of food
      provides subjects a choice of food and non-food alternatives, and defines the
      relative reinforcing value of food based on the allocation of responses for the
      two alternatives as the schedules of reinforcement for the alternatives change.
      Greater allocation of responses for one alternative versus another reflects the
      relative reinforcing value of the alternatives. This method was designed for
      laboratory use, but methods are needed to extend measurement of reinforcing value
      to applied research environments. Two experiments were conducted to assess the
      validity of a questionnaire measure of the relative reinforcing value of food in
      normal weight university samples. Study 1 (n=39) assessed the relationship
      between the relative reinforcing value of snack food versus fruits and vegetables
      (condition 1) or enjoyable sedentary behaviors (condition 2) as measured by the
      questionnaire and standardized computerized concurrent schedules criterion. A
      significant relationship (Pearson r=0.49, p<0.01; Guttman's MU2=0.69) across the
      two conditions between the two methods of measuring food reinforcement was
      observed. Experiment 2 (n=10) utilized a within-subject counterbalanced design to
      manipulate food deprivation and hunger levels to determine if food deprivation
      increased the reinforcing value of snack food as measured by the questionnaire to
      provide an index of validity of the questionnaire. Results showed that food
      deprivation increased the relative reinforcing value of snack food. Results from
      both studies suggest that the questionnaire has good validity, and may represent
      an efficient and reliable method of assessing the relative reinforcing value of
      food.

PMID- 15854875
TI  - Is population-level perversity a likely outcome of mass vaccination against HIV?

PMID- 15854877
TI  - Global climate change and malaria.

PMID- 15854880
TI  - "Detox", a mass delusion.

PMID- 15854878
TI  - Global climate change and malaria.

PMID- 15854881
TI  - Postwar re-restablishment and activation of laboratory capacity for disease
      surveillance in southern Iraq, 2003.

PMID- 15854883
TI  - Community-acquired meticillin-resistant Staphylococcus aureus: an emerging
      threat.
AB  - Community-acquired meticillin-resistant Staphylococcus aureus (MRSA) is becoming
      an important public-health problem. New strains of S aureus displaying unique
      combinations of virulence factors and resistance traits have been associated with
      high morbidity and mortality in the community. Outbreaks of epidemic furunculosis
      and cases of severe invasive pulmonary infections in young, otherwise healthy
      people have been particularly noteworthy. We review the characteristics of these
      new strains of community-acquired MRSA that have contributed to their
      pathogenicity and discuss new approaches to the diagnosis and management of
      suspected and confirmed community-acquired MRSA infections.

PMID- 15854884
TI  - Management of anthrax meningitis.
AB  - Meningitis due to infection with Bacillus anthracis is considered an infrequent
      manifestation of the disease but one associated with high mortality. The
      bioterrorism event in the USA in the autumn of 2001 demonstrated our need for a
      better understanding of anthrax meningitis, as well as management and
      antimicrobial therapy. However, human clinical trials are not possible and animal
      experiments to guide such therapy are limited. An approach to the treatment of
      anthrax meningitis, based on the pathogenicity of B anthracis, the
      pharmacokinetics and pharmacodynamics of individual antimicrobial agents, studies
      of anthrax post-exposure prophylaxis in non-human primates, experience with
      antimicrobial susceptibility patterns of the 2001 outbreak strain, and the
      clinical experience with inhalational anthrax cases during the 2001 outbreak is
      presented. These outbreak data, the failure of previous single-drug regimens, the
      concerns of resistance, and the need for coverage for other causes of bacterial
      mengingitis suggest initial treatment of suspected anthrax meningitis should
      anchor on an intravenous fluoroquinolone and should include one or two other
      agents with activity against B anthracis and good penetration into the central
      nervous system. Such other agents include penicillin, ampicillin, meropenem,
      vancomycin, and rifampicin.

PMID- 15854885
TI  - Is hepatitis C virus infection of dendritic cells a mechanism facilitating viral
      persistence?
AB  - More than 170 million people worldwide are chronically infected with hepatitis C
      virus (HCV), which is a major cause of chronic hepatitis, cirrhosis, and
      hepatocellular carcinoma. Impaired T-cell reactivity to HCV, a hallmark of
      inefficient adaptive immunity, is believed to be responsible for the high
      propensity of HCV to cause chronic infection. Dendritic cells are the most potent
      antigen-presenting cells and many viruses affect various dendritic cell
      functions. Data suggest that such changes induced by HCV may have an important
      role in viral persistence. HCV has been shown to bind to dendritic cells,
      although viral replication within these cells occurs at a very low level.
      Dendritic cells from people with chronic HCV infection are impaired in their
      capacity to stimulate T cells. This impairment may be a consequence of changes in
      the expression of major histocompatibility complex and costimulatory molecules on
      its surface, as well as in the production of cytokines such as interleukin 12. In
      addition, hepatic dendritic cells may be affected by the tolerogenic
      microenvironment of the liver, possibly generating dendritic cells that promote
      regulatory T cells, which suppress the cellular immune response mounted against
      HCV.

PMID- 15854886
TI  - Computer-assisted decision support for the diagnosis and treatment of infectious
      diseases in intensive care units.
AB  - Diagnosing nosocomial infections in critically ill patients admitted to intensive
      care units (ICUs) is a challenge because signs and symptoms are usually non
      specific for a particular infection. In addition, the choice of treatment, or the
      decision not to treat, can be difficult. Models and computer-based decision
      support systems have been developed to assist ICU physicians in the management of
      infectious diseases. We discuss the historical development, possibilities, and
      limitations of various computer-based decision-support models for infectious
      diseases, with special emphasis on Bayesian approaches. Although Bayesian
      decision-support systems are potentially useful for medical decision making in
      infectious disease management, clinical experience with them is limited and
      prospective evaluation is needed to determine whether their use can improve the
      quality of patient care.

PMID- 15854887
TI  - Clinical examination and laboratory tests for estimation of trachoma prevalence
      in a remote setting: what are they really telling us?
AB  - Worldwide, an estimated 84 million people have active trachoma and 7.6 million
      people have trachomatous trichiasis. WHO's SAFE strategy is an effective tool in
      the worldwide effort to eliminate blinding trachoma, but its institution and
      monitoring requires a simple, reliable, and cost-effective method to detect
      disease. To date, clinical examination has provided the main method of diagnosis.
      Detection of Chlamydia trachomatis with nucleic acid amplification tests does not
      always correlate well with clinical findings, which has prompted the suggestion
      that these methods should replace clinical examination. However, a review of the
      research carried out in animals and human beings suggests the relation between
      laboratory tests and clinical examination is due to the kinetics of trachoma and
      not to an inherent problem in either detection system. Given the increased
      difficulties of using laboratory tests in parts of the world where trachoma is
      endemic, we should not abandon clinical grading as a tool to assess the need for,
      and the effectiveness of, trachoma intervention programmes.

PMID- 15854888
TI  - Extrahepatic manifestations in transgenic mice of osteopontin in hepatocytes-A
      clue to advent of pathological state in various organs of chronic hepatitis C
      patients.
AB  - Osteopontin is a cytokine essential for initiation of Th1 immune reaction. We
      established transgenic mice expressing osteopontin in hepatocyte, in which liver
      necrosis with lymphocyte infiltration developed gradually from 12 weeks of age
      with up-regulated osteopontin levels in the circulation, suggesting that
      extrahepatic manifestations might also occur as a result of excessive Th1 immune
      reaction. We examined histological and immunohistochemical features of various
      organs in these mice. Splenomegaly and enlargement of lymph nodes around the
      liver and intestine became apparent with marked infiltration of small lymphocytes
      in the transgenic mice later than 24 weeks of age. Immunostaining revealed that
      lymphocytes in the spleen and lymph nodes were positive for either CD3 or CD20,
      suggesting that the infiltrating lymphocytes were both B and T cells. Similar
      lymphocyte infiltration was found in the lung, kidney and submandibular gland.
      Alveolar septa became hypertrophic with lymphocyte infiltration, and the lung
      showed the appearance of interstitial pneumonia. These lesions are similar to
      extrahepatic manifestations in chronic hepatitis C patients, suggesting that
      augmented Th1 immune reaction to hepatitis C virus (HCV) proteins or the proteins
      with molecular mimicry of HCV may be a contributing factor for the formation of
      the pathological state not only in the liver but also in various organs under
      chronic infection of hepatitis C virus.

PMID- 15854889
TI  - Autophagy.

PMID- 15854890
TI  - Selection and the origin of species.

PMID- 15854891
TI  - Shortest recorded vertebrate lifespan found in a coral reef fish.

PMID- 15854892
TI  - Plant genetics: when not to interfere.
AB  - New evidence suggests that the model plant Arabidopsis has two biochemically
      distinct pathways that produce genetic crossovers. Studies in several organisms
      have revealed that one kind of crossover regulation - crossover interference - is
      applied differently from species to species. Arabidopsis appears to use an
      interference system similar to that of budding yeast.

PMID- 15854893
TI  - Genetic imprinting: conflict at the Callipyge locus.
AB  - The imprinted Dlk1-Gtl2 region of the mammalian genome - which in sheep
      encompasses the Callipyge locus, known for its unusual mode of inheritance -
      encodes a number of maternally expressed miRNAs. Five of these miRNAs, hosted by
      the antisense transcript antiPeg11, have now been shown to target degradation of
      the paternally expressed Peg11 mRNA by an RNAi-mediated mechanism.

PMID- 15854894
TI  - Neuronal networks: flip-flops in the brain.
AB  - Neuronal activity can rapidly flip-flop between stable states. Although these
      semi-stable states can be generated through interactions of neuronal networks, it
      is now known that they can also occur in vivo through intrinsic ionic currents.

PMID- 15854895
TI  - Animal phylogeny: fatal attraction.
AB  - MPhylogenetic analyses of hundreds of genes from model animals have placed flies
      closer to vertebrates than to nematodes; recent work suggests this may be due to
      an artefact known as long branch attraction.

PMID- 15854896
TI  - Microtubules: a ring for the depolymerization motor.
AB  - Newly discovered rings around microtubules, assembled from the Dam1 protein
      complex, may provide the dynamic linkage at microtubule ends for force generation
      coupled to microtubule depolymerization and polymerization.

PMID- 15854897
TI  - Axon regeneration: it's getting crowded at the gates of TROY.
AB  - A novel neuronal receptor complex that mediates myelin's inhibitory action on
      nerve fiber regeneration has at last been identified. This discovery could be an
      important step towards promoting nerve regeneration after stroke or spinal cord
      injury.

PMID- 15854898
TI  - Actin nucleation: spire - actin nucleator in a class of its own.
AB  - The rate limiting step for actin filament polymerisation is nucleation, and two
      types of nucleator have been described: the Arp2/3 complex and the formins. A
      recent study has now identified in Spire a third class of actin nucleator. The
      four short WH2 repeats within Spire bind four consecutive actin monomers to form
      a novel single strand nucleus for 'barbed end' actin filament elongation.

PMID- 15854899
TI  - Senescence: even bacteria get old.
AB  - Cellular senescence, even in the presence of abundant nutrients, has now been
      demonstrated in several microbes, including most recently the bacterium
      Escherichia coli, suggesting that it may be a universal adaptive response to the
      inevitable damage to cell constituents that accumulates with time.

PMID- 15854900
TI  - Cytokinesis: new roles for myosin.
AB  - Myosin II is the motor for cytokinesis, an event at the end of cell division
      during which the animal cell uses a contractile ring to pinch itself in half. New
      and surprising research shows that myosin, either through light chain
      phosphorylation or through its ATPase activity, also plays an important role in
      both the assembly and disassembly of the actin contractile ring.

PMID- 15854901
TI  - Two meiotic crossover classes cohabit in Arabidopsis: one is dependent on
      MER3,whereas the other one is not.
AB  - BACKGROUND: Crossovers are essential for the completion of meiosis. Recently, two
      pathways of crossover formation have been identified on the basis of distinct
      genetic controls. In one pathway, crossover inhibits the occurrence of another
      such event in a distance-dependent manner. This phenomenon is known as
      interference. The second kind of crossover is insensitive to interference. The
      two pathways function independently in budding yeast. Only interference
      insensitive crossovers occur in Schizosaccharomyces pombe. In contrast, only
      interference-sensitive crossovers occur in Caenorabditis elegans. The situation
      in mammals and plants remains unclear. Mer3 is one of the genes shown to be
      required for the formation of interference-sensitive crossovers in Saccharomyces
      cerevisiae. RESULTS: To unravel the crossover status in the plant Arabidopsis
      thaliana, we investigated the role of the A. thaliana MER3 gene through the
      characterization of a series of allelic mutants. All mer3 mutants showed low
      levels of fertility and a significant decrease (about 75%) but not a total
      disappearance of meiotic crossovers, with the number of recombination events
      initiated in the mutants being similar to that in the wild-type. Genetic analyses
      showed that the residual crossovers in mer3 mutants did not display interference
      in one set of adjacent intervals. CONCLUSIONS: Mutation in MER3 in Arabidopsis
      appeared to be specific to recombination events resulting in interference
      sensitive crossovers. Thus, MER3 function is conserved from yeast to plants and
      may exist in other metazoans. Arabidopsis therefore has at least two pathways for
      crossover formation, one giving rise to interference-sensitive crossover and the
      other to independently distributed crossovers.

PMID- 15854902
TI  - Rheb binds and regulates the mTOR kinase.
AB  - BACKGROUND: The target of rapamycin (TOR), in complex with the proteins raptor
      and LST8 (TOR complex 1), phosphorylates the p70S6K and 4E-BP1 to promote mRNA
      translation. Genetic evidence establishes that TOR complex activity in vivo
      requires the small GTPase Rheb, and overexpression of Rheb can rescue TOR from
      inactivation in vivo by amino-acid withdrawal. The Tuberous Sclerosis heterodimer
      (TSC1/TSC2) functions as a Rheb GTPase activator and inhibits TOR signaling in
      vivo. RESULTS: Here, we show that Rheb binds to the TOR complex specifically,
      independently of its ability to bind TSC2, through separate interactions with the
      mTOR catalytic domain and with LST8. Rheb binding to the TOR complex in vivo and
      in vitro does not require Rheb guanyl nucleotide charging but is modulated by GTP
      and impaired by certain mutations (Ile39Lys) in the switch 1 loop. Nucleotide
      deficient Rheb mutants, although capable of binding mTOR in vivo and in vitro,
      are inhibitory in vivo, and the mTOR polypeptides that associate with nucleotide
      deficient Rheb in vivo lack kinase activity in vitro. Reciprocally, mTOR
      polypeptides bound to Rheb(Gln64Leu), a mutant that is nearly 90% GTP charged,
      exhibit substantially higher protein kinase specific activity than mTOR bound to
      wild-type Rheb. CONCLUSIONS: The TOR complex 1 is a direct target of Rheb-GTP,
      whose binding enables activation of the TOR kinase.

PMID- 15854903
TI  - The Nef protein of human immunodeficiency virus establishes superinfection
      immunity by a dual strategy to downregulate cell-surface CCR5 and CD4.
AB  - BACKGROUND: Viruses frequently render cells refractory to subsequent infection
      with the same virus. This state of superinfection immunity counteracts
      potentially detrimental consequences for the infected cell and facilitates high
      level replication and viral spread in the host. RESULTS: Here, we show that human
      immunodeficiency virus (HIV) employs its early gene product Nef to efficiently
      interfere with superinfection at the viral-entry step. In this context, we
      identify the downregulation of cell-surface CCR5, the major HIV coreceptor, as a
      novel and highly conserved activity of Nef. Nef targets the CCR5 coreceptor and
      the HIV binding receptor CD4 via distinct cellular machineries to enhance the
      endocytosis rate of both HIV receptor components and to accelerate their
      degradation. Functionally, these genetically separable actions by Nef synergized
      to efficiently protect cells from HIV superinfection at the level of fusion of
      the viral envelope with the plasma membrane. CONCLUSIONS: HIV has evolved two
      independent activities for Nef to downregulate the receptor complex and to
      facilitate its efficient replication and spread. This evasion strategy likely
      represents a mechanism by which the pathogenicity factor Nef elevates viral
      replication in vivo and thus promotes AIDS pathogenesis.

PMID- 15854904
TI  - Myosin-II-dependent localization and dynamics of F-actin during cytokinesis.
AB  - BACKGROUND: The assembly of an F-actin- and myosin-II-containing contractile ring
      (CR) is required for cytokinesis in eukaryotic cells. Interactions between myosin
      II and actin in the ring are believed to generate the force that constricts the
      cell into two daughters. The mechanism(s) that contribute to the spatially and
      temporally regulated assembly and disassembly of the CR at the cell equator are
      poorly understood. RESULTS: We generated an LLCPK1 epithelial cell line that
      stably expresses GFP-actin. Live confocal imaging showed accumulation of GFP
      actin in the equatorial cortex from late anaphase through cytokinesis.
      Fluorescence recovery after photobleaching (FRAP) experiments showed that actin
      in the CR is highly dynamic (t(1/2) = 26 s). In some cells, movement of GFP-actin
      toward the equatorial region was observed and contributed to FRAP. Blocking actin
      dynamic turnover with jasplakinolide demonstrates that dynamic actin is required
      for CR formation and cytokinesis. To test the role of myosin II in actin turnover
      and transport during CR formation, we inhibited myosin light-chain kinase with
      ML7 and myosin II ATPase activity with blebbistatin. Inhibition of myosin light
      chain phosphorylation resulted in clearance of GFP-actin from the equatorial
      region, a reduction in myosin II in the furrow, and inhibition of cytokinesis.
      Treatment with blebbistatin did not block CR formation but reduced FRAP of GFP
      actin and prevented completion of cytokinesis. CONCLUSIONS: These results
      demonstrate that the majority of actin in the CR is highly dynamic and establish
      novel roles for myosin II in the retention and dynamic turnover of actin in the
      CR.

PMID- 15854905
TI  - Cortical actin turnover during cytokinesis requires myosin II.
AB  - The involvement of myosin II in cytokinesis has been demonstrated with
      microinjection, genetic, and pharmacological approaches; however, the exact role
      of myosin II in cell division remains poorly understood. To address this
      question, we treated dividing normal rat kidney (NRK) cells with blebbistatin, a
      potent inhibitor of the nonmuscle myosin II ATPase. Blebbistatin caused a strong
      inhibition of cytokinesis but no detectable effect on the equatorial localization
      of actin or myosin. However, whereas these filaments dissociated from the equator
      in control cells during late cytokinesis, they persisted in blebbistatin-treated
      cells over an extended period of time. The accumulation of equatorial actin was
      caused by the inhibition of actin filament turnover, as suggested by a 2-fold
      increase in recovery half-time after fluorescence photobleaching. Local release
      of blebbistatin at the equator caused localized accumulation of equatorial actin
      and inhibition of cytokinesis, consistent with the function of myosin II along
      the furrow. However, treatment of the polar region also caused a high frequency
      of abnormal cytokinesis, suggesting that myosin II may play a second, global
      role. Our observations indicate that myosin II ATPase is not required for the
      assembly of equatorial cortex during cytokinesis but is essential for its
      subsequent turnover and remodeling.

PMID- 15854906
TI  - A novel ADP/ATP transporter in the mitosome of the microaerophilic human parasite
      Entamoeba histolytica.
AB  - Recent data suggest that microaerophilic and parasitic protozoa, which lack
      oxidative phosphorylation, nevertheless contain mitochondrial homologs [1-6],
      organelles that share common ancestry with mitochondria. Such widespread
      retention suggests there may be a common function for mitochondrial homologs that
      makes them essential for eukaryotic cells. We determined the mitochondrial
      carrier family (MCF) complement of the Entamoeba histolytica mitochondrial
      homolog, also known as a crypton [5] or more commonly as a mitosome [3]. MCF
      proteins support mitochondrial metabolic energy generation, DNA replication, and
      amino-acid metabolism by linking biochemical pathways in the mitochondrial matrix
      with those in the cytosol [7]. MCF diversity thus closely mirrors important
      facets of mitochondrial metabolic diversity. The Entamoeba histolytica mitosome
      has lost all but a single type of MCF protein, which transports ATP and ADP via a
      novel mechanism that is not reliant on a membrane potential. Phylogenetic
      analyses confirm that the Entamoeba ADP/ATP carrier is distinct from archetypal
      mitochondrial ADP/ATP carriers, an observation that is supported by its different
      substrate and inhibitor specificity. Because many functions of yeast and human
      mitochondria rely on solutes transported by specialized members of this family,
      the Entamoeba mitosome must contain only a small subset of these processes
      requiring adenine nucleotide exchange.

PMID- 15854907
TI  - RNAi-mediated allelic trans-interaction at the imprinted Rtl1/Peg11 locus.
AB  - The Dlk1-Gtl2 imprinted domain, encompassing the callipyge (CLPG) locus in sheep,
      has recently been shown to harbor a large number of maternally expressed miRNA
      genes [1, 2]. Two of these (mir127 and mir136) are processed from a transcript
      (antiPeg11) that is antisense to Rtl1/Peg11, a paternally expressed intronless
      gene with homology to the gag and pol polyproteins of Sushi-like retroelements
      [3]. We herein demonstrate that several additional miRNAs are processed from
      antiPeg11 and that these regulate Rtl1/Peg11 in trans by guiding RISC-mediated
      cleavage of its mRNA. This is the first demonstration of miRNA-mediated RNAi
      involving imprinted genes in mammals.

PMID- 15854908
TI  - Loss of function of MULTICOPY SUPPRESSOR OF IRA 1 produces nonviable
      parthenogenetic embryos in Arabidopsis.
AB  - In sexually reproducing species, fertilization brings together in the zygote the
      genomes of the female and male gametes. In several animal species, female gametes
      are able to initiate embryogenesis in the absence of fertilization, a process
      referred to as parthenogenesis. Parthenogenesis has been engineered in mice by
      tampering with expression of loci under epigenetic controls [1]. In plants,
      embryo development in the absence of fertilization has been reported in cases in
      which meiosis is bypassed leading to apomictic development, and parthenogenetic
      development from a reduced egg cell has been only reported in rare accidental
      cases [2]. We report that single mutations in the gene MULTICOPY SUPPRESSOR OF
      IRA 1 (MSI1) are able to initiate parthenogenetic development of the embryo in
      Arabidopsis thaliana from eggs cells produced by meiosis. The WD40 repeat protein
      MSI1 is part of the evolutionarily conserved Polycomb group (PcG) chromatin
      remodeling complexes [3] and is homologous to the Retinoblastoma binding proteins
      P55 in Drosophila and RbAp48 in mammals [4]. Nonviable haploid parthenogenetic
      msi1 embryos express molecular markers and polarity similar to diploid wild-type
      (wt) embryos produced by fertilization, indicating a maternal contribution to
      early patterning of the Arabidopsis embryo.

PMID- 15854909
TI  - humpty dumpty is required for developmental DNA amplification and cell
      proliferation in Drosophila.
AB  - The full complement of proteins required for the proper regulation of genome
      duplication are yet to be described. We employ a genetic DNA-replication model
      system based on developmental amplification of Drosophila eggshell (chorion)
      genes [1]. Hypomorphic mutations in essential DNA replication genes result in a
      distinct thin-eggshell phenotype owing to reduced amplification [2]. Here, we
      molecularly identify the gene, which we have named humpty dumpty (hd),
      corresponding to the thin-eggshell mutant fs(3)272-9 [3]. We confirm that hd is
      essential for DNA amplification in the ovary and show that it also is required
      for cell proliferation during development. Mosaic analysis of hd mutant cells
      during development and RNAi in Kc cells reveal that depletion of Hd protein
      results in severe defects in genomic replication and DNA damage. Most Hd protein
      is found in nuclear foci, and some may traverse the nuclear envelope. Consistent
      with a role in DNA replication, expression of Hd protein peaks during late G1 and
      S phase, and it responds to the E2F1/Dp transcription factor. Hd protein sequence
      is conserved from plants to humans, and published microarrays indicate that
      expression of its putative human ortholog also peaks at G1/S [4]. Our data
      suggest that hd defines a new gene family likely required for cell proliferation
      in all multicellular eukaryotes.

PMID- 15854910
TI  - Cleaner shrimp use a rocking dance to advertise cleaning service to clients.
AB  - Signals transmit information to receivers about sender attributes, increase the
      fitness of both parties, and are selected for in cooperative interactions between
      species to reduce conflict [1, 2]. Marine cleaning interactions are known for
      stereotyped behaviors [3-6] that likely serve as signals. For example, "dancing"
      and "tactile dancing" in cleaner fish may serve to advertise cleaning services to
      client fish [7] and manipulate client behavior [8], respectively. Cleaner shrimp
      clean fish [9], yet are cryptic in comparison to cleaner fish. Signals,
      therefore, are likely essential for cleaner shrimp to attract clients. Here, we
      show that the yellow-beaked cleaner shrimp [10] Urocaridella sp. c [11] uses a
      stereotypical side-to-side movement, or "rocking dance," while approaching
      potential client fish in the water column. This dance was followed by a cleaning
      interaction with the client 100% of the time. Hungry cleaner shrimp, which are
      more willing to clean than satiated ones [12], spent more time rocking and in
      closer proximity to clients Cephalopholis cyanostigma than satiated ones, and
      when given a choice, clients preferred hungry, rocking shrimp. The rocking dance
      therefore influenced client behavior and, thus, appears to function as a signal
      to advertise the presence of cleaner shrimp to potential clients.

PMID- 15854911
TI  - IP3 receptor activity is differentially regulated in endoplasmic reticulum
      subdomains during oocyte maturation.
AB  - Fertilization competency results from hormone-induced remodeling of oocytes into
      eggs. The signaling pathways that effect this change exemplify bistability, where
      brief hormone exposure irrevocably switches cell fate. In Xenopus, changes in
      Ca(2+) signaling epitomize such remodeling: The reversible Ca(2+) signaling
      phenotype of oocytes rapidly adapts to support irreversible propagation of the
      fertilization Ca(2+) wave. Here, we simultaneously resolved IP(3) receptor
      (IP(3)R) activity with endoplasmic reticulum (ER) structure to optically dissect
      the functional architecture of the Ca(2+) release apparatus underpinning this
      reorganization. We show that changes in Ca(2+) signaling correlate with IP(3)R
      redistribution from specialized ER substructures called annulate lamellae (AL),
      where Ca(2+) release activity is attenuated, into IP(3)R-replete patches in the
      cortical ER of eggs that support the fertilization Ca(2+) wave. These data show:
      first, that IP(3)R sensitivity is regulated with high spatial acuity even between
      contiguous ER regions; and second, that drastic reorganization of Ca(2+)
      signaling dynamics can be driven by subcellular redistribution in the absence of
      changes in channel number or molecular or familial Ca(2+) channel diversity.
      Finally, these results define a novel role for AL in Ca(2+) signaling. Because AL
      are prevalent in other scenarios of rapid cell division, further studies of their
      impact on Ca(2+) signaling are warranted.

PMID- 15854912
TI  - The CENP-F-like proteins HCP-1 and HCP-2 target CLASP to kinetochores to mediate
      chromosome segregation.
AB  - During chromosome segregation, kinetochores form dynamic connections with spindle
      microtubules. In vertebrates, these attachments require the activities of a
      number of outer kinetochore proteins, including CENP-F [1, 2] and the widely
      conserved microtubule-associated protein CLASP [3]. Here, we investigate the
      functional relationship between HCP-1/2, two redundant CENP-F-like proteins, and
      CLASP(CLS-2) in Caenorhabditis elegans. HCP-1/2 and CLASP(CLS-2) localize
      transiently to mitotic C. elegans kinetochores with nearly identical kinetic
      profiles, and biochemical purifications demonstrate that they also associate
      physically. In embryos depleted of HCP-1/2, CLASP(CLS-2) no longer localizes to
      chromosomes, whereas CLASP(CLS-2) depletion does not prevent HCP-1/2 targeting.
      Consistent with the localization dependency and biochemical association,
      depletion of HCP-1/2 or CLASP(CLS-2) resulted in virtually identical defects in
      mitotic chromosome segregation characterized by a failure of sister-chromatid
      biorientation. This phenotype could be partially suppressed by disrupting the
      astral forces that pull spindle poles apart in the 1 cell embryo, indicating that
      CLASP(CLS-2) is required for biorientation when chromosome-spindle attachments
      are subjected to poleward force. Our results establish that the key role of HCP
      1/2 is to target CLASP(CLS-2) to kinetochores, and they support the recently
      proposed model that CLASP functions to promote the polymerization of kinetochore
      bound microtubules [4].

PMID- 15854913
TI  - Phosphorylation of ZEN-4/MKLP1 by aurora B regulates completion of cytokinesis.
AB  - The central spindle regulates the formation and positioning of the contractile
      ring and is essential for completion of cytokinesis [1]. Central spindle assembly
      begins in early anaphase with the bundling of overlapping, antiparallel,
      nonkinetochore microtubules [2, 3], and these bundles become compacted and mature
      into the midbody. Prominent components of the central spindle include aurora B
      kinase and centralspindlin, a complex containing a Kinesin-6 protein (ZEN
      4/MKLP1) and a Rho family GAP (CYK-4/MgcRacGAP) that is essential for central
      spindle assembly [4]. Centralspindlin localization depends on aurora B kinase
      [5]. Aurora B concentrates in the midbody and persists between daughter cells.
      Here, we show that in C. elegans embryos and in cultured human cells,
      respectively, ZEN-4 and MKLP1 are phosphorylated by aurora B in vitro and in vivo
      on conserved C-terminal serine residues. In C. elegans embryos, a
      nonphosphorylatable mutant of ZEN-4 localizes properly but does not efficiently
      support completion of cytokinesis. In mammalian cells, an inhibitor of aurora
      kinase acutely attenuates phosphorylation of MKLP1. Inhibition of aurora B in
      late anaphase causes cytokinesis defects without disrupting the central spindle.
      These data indicate a conserved role for aurora-B-mediated phosphorylation of ZEN
      4/MKLP1 in the completion of cytokinesis.

PMID- 15854914
TI  - Planar cell polarity genes regulate polarized extracellular matrix deposition
      during frog gastrulation.
AB  - The noncanonical wnt/planar cell polarity (PCP) pathway [1] regulates the
      mediolaterally (planarly) polarized cell protrusive activity and intercalation
      that drives the convergent extension movements of vertebrate gastrulation [2],
      yet the underlying mechanism is unknown. We report that perturbing expression of
      Xenopus PCP genes, Strabismus (Xstbm), Frizzled (Xfz7), and Prickle (Xpk),
      disrupts radially polarized fibronectin fibril assembly on mesodermal tissue
      surfaces, mediolaterally polarized motility, and intercalation. Polarized
      motility is restored in Xpk-perturbed explants but not in Xstbm- or Xfz7
      perturbed explants cultured on fibronectin surfaces. The PCP complex, including
      Xpk, first regulates polarized surface assembly of the fibronectin matrix, which
      is necessary for mediolaterally polarized motility, and then, without Xpk, has an
      additional and necessary function in polarizing motility. These results show that
      the PCP complex regulates several cell polarities (radial, planar) and several
      processes (matrix deposition, motility), by indirect and direct mechanisms, and
      acts in several modes, either with all or a subset of its components, during
      vertebrate morphogenesis.

PMID- 15854915
TI  - Nontraumatic chest wall systemic-to-pulmonary artery fistula.
AB  - A congenital chest wall systemic-to-left pulmonary artery fistula fed by the left
      internal mammary and left gastric arteries in a 31-year-old man is reported.
      Attempted sclerosis was complicated by rupture of the communicating vessel,
      hemothorax, and deep vein thrombosis of the legs. Fistula resection and pulmonary
      decortication were successfully performed.

PMID- 15854916
TI  - Trans-arterial infusion chemotherapy for recurrence of pleural dissemination
      after thymectomy.
AB  - We present a report of trans-arterial infusion chemotherapy through the
      intercostal arteries and subphrenic artery for pleural dissemination of recurrent
      thymoma after thymectomy. The disseminated tumor did not enlarge for more than a
      year after this treatment, and there were no side effects. Trans-arterial
      infusion chemotherapy appears to be a preferable procedure for pleural
      dissemination of thymoma.

PMID- 15854917
TI  - The future of cardiac surgery: the times, they are a changin'.

PMID- 15854918
TI  - Feasibility of valve repair for regurgitant bicuspid aortic valves--an
      echocardiographic study.
AB  - BACKGROUND: There is increasing interest in the role of valve repair for patients
      with isolated severe aortic regurgitation. Those with bicuspid aortic valves are
      suggested as most suitable for repair. Morphologic features of these valves that
      suggest feasibility of repair are not well defined. METHODS: Perioperative
      echocardiograms on 132 consecutive patients (mean age 42 +/- 12 years; 94% male),
      with bicuspid valves and isolated aortic regurgitation undergoing surgery at our
      institution were reviewed. Seventy-five patients (57%) underwent successful valve
      repair. Repair was attempted but unsuccessful for another 8 patients (6
      intraoperatively and 2 before discharge). RESULTS: Cusp prolapse was the most
      common primary mechanism of regurgitation (88 patients [67%]), with 81 patients
      having primarily eccentrically directed regurgitation. Echocardiographic
      examination of 72 (55%) had evidence of cusp thickening with 40 (30%) having cusp
      calcification. By multivariate analysis, an eccentric regurgitant jet direction
      (odds ratio = 14.3; 95% confidence interval [CI] = 3.4 to 59.6), lack of cusp
      thickening (odds ratio = 5.9 [1.7 to 20]), lack of cusp calcification (odds ratio
      = 4.2; [1.1 to 16.7]) and the absence of commissural thickening (odds ratio = 4.8
      [1.3 to 16.7]) were independently associated with a greater likelihood of
      successful valve repair. Greater cusp thickening was the only factor associated
      with attempted but failed repair. CONCLUSIONS: Successful repair of regurgitant
      bicuspid aortic valves was more feasible for those patients with eccentric
      regurgitant jets, those without cusp or commissural thickening or cusp
      calcification. Recognition of these features may enhance patient selection and
      improve procedural outcomes with aortic valve repair.

PMID- 15854919
TI  - Aortic valve periprosthetic leakage: anatomic observations and surgical results.
AB  - BACKGROUND: One of the most frequent causes of reoperation after heart valve
      replacement is periprosthetic leakage (PPL). Previous studies have failed to
      determine whether PPL is linked to specific anatomic details. The aim of this
      study was to examine the location within the aortic annulus where PPL occurs, and
      to evaluate the postoperative outcome after surgical correction. METHODS: Between
      January 1985 and December 2001, 28 patients underwent reoperation because of PPL
      after aortic valve replacement. The aortic annulus was analyzed in a clockwise
      format with hour 1 corresponding to the commissure between the left coronary
      sinus and the right coronary sinus, hour 5 to the commissure between the right
      coronary sinus and the noncoronary sinus, and hour 9 to the commissure between
      the noncoronary sinus and the left coronary sinus. RESULTS: Overall operative
      mortality was 7.1% (2 patients). Repair of PPL was carried out in 8 patients
      whereas prosthetic valve replacement was necessary in 20 patients. Urgency or
      emergency operation (p < 0.0037), preoperative New York Heart Association class
      IV (p < 0.04), need for prosthetic valve replacement (p = 0.05), and implant of
      mechanical valve (p = 0.031) were independent determinants of dismal prognosis.
      Periprosthetic leakage occurred more frequently between hour 4 and hour 8 (19
      patients), with the risk of leakage being two times greater than in other annular
      areas. CONCLUSIONS: Our study suggests that PPL occurs more frequently in a
      specific portion of the peculiar aortic annulus. In case of PPL diagnosis, a
      timely reoperation might decrease operative risks by avoiding emergency
      procedures and unfavorable preoperative clinical conditions, and preventing
      prosthetic valve replacement.

PMID- 15854920
TI  - Aortic valve translocation for severe prosthetic valve endocarditis: early
      results and long-term follow-up.
AB  - BACKGROUND: Surgical management of ventriculo-aortic disconnection and aortic
      root abscesses after prosthetic aortic valve endocarditis carries high mortality
      and morbidity. Initial experience with translocation of the aortic valve and
      distal coronary artery bypass grafting was disappointing in terms of short-term
      and long-term success in the few published reports. We describe a technique of
      translocation of the aortic valve into the ascending aorta with direct antegrade
      myocardial revascularization. METHODS: Between 1980 and 1992, we included 21
      patients and evaluated their long-term outcome. The surgical technique included
      extracting the aortic valve prosthesis, resecting all infected tissue, restoring
      the left ventricular outflow tract, and translocating the aortic valve into the
      ascending aorta, associated with myocardial revascularization of the left main
      trunk and the proximal right coronary artery. RESULTS: All patients required
      emergency surgery: 15 patients were in severe congestive heart failure, 3
      patients were in cardiogenic shock, and 3 patients had multiple neurologic and
      peripheral signs of distal embolization. Fifteen patients had active prosthetic
      valve endocarditis. Intraoperative findings dictated the translocation. The
      overall hospital mortality was 14%. None of the 18 hospital survivors had
      prosthetic aortic valve endocarditis recurrence. All patients were observed from
      12 to 22 years, are alive, and have resumed normal activities. CONCLUSIONS: In
      severe forms of prosthetic valve endocarditis, this technique provides a safe and
      reliable alternative to homograft replacement. The long-term results are
      satisfactory.

PMID- 15854921
TI  - Valve-related events after aortic root replacement with cryopreserved aortic
      homografts.
AB  - BACKGROUND: Aortic root replacement with aortic homografts for various pathologic
      conditions involving the aortic root has yielded good early results. To assess
      mid-term valve-related events, a follow-up study was conducted. METHODS: From
      February 1989 through January 2003, 213 patients with a mean age of 51.3 +/- 11.8
      years underwent aortic root replacement with a cryopreserved aortic homograft.
      Bacterial endocarditis (58.7%) was the predominant indication for surgery (native
      valve endocarditis, n = 73; prosthetic valve endocarditis, n = 52). Of the 197
      hospital survivors, 194 were entered in the follow-up study (98.5% complete).
      Endpoints of the study were death, valve-related death, reoperation for valve
      failure, endocarditis, thromboembolic events, and anticoagulant-related bleeding
      events. Follow-up was conducted between February and April 2003. RESULTS: Overall
      hospital mortality was 7.5% (n = 16; 70% confidence limits, 5.6% to 9.4%). Mean
      follow-up was 5.8 years (range, 0.3 to 14.3). In total, 20 late deaths occurred
      (10.3%); of these, 5 were valve-related. The overall survival at 5 and 10 years
      is 87.3% +/- 2.4% and 70.8% +/- 5.3%, respectively. Twenty-one patients (10.8%)
      required reoperation, either for structural valve deterioration (n = 12), false
      aneurysm (n = 3), endocarditis of the homograft (n = 3), or for other reason (n =
      3). Mortality for reoperation was 28.6% (n = 6). Five-year and 10-year freedom
      from reoperation is 94.5% +/- 1.8% and 76.4% +/- 5.3%, respectively. Endocarditis
      of the homograft was reported in 4 patients (3.2%), of whom 1 patient was treated
      medically and 3 required reoperation. Thromboembolic events (n = 1) and
      anticoagulant-related bleeding events (n = 0) were rarely seen. A recent
      echocardiographic study was available in 124 patients (71.3%). Aortic
      regurgitation grade I to II was reported in 121 patients (97.6%). CONCLUSIONS:
      Cryopreserved aortic homografts function well on mid-term evaluation. The
      incidence of structural valve failure is acceptable. Reoperations for homograft
      endocarditis carry a high mortality rate.

PMID- 15854922
TI  - Minimally invasive mitral valve repair in the context of Barlow's disease.
AB  - BACKGROUND: The aim of this study is to report our overall experience with
      minimally invasive mitral valve repair for correction of severe mitral
      regurgitation in the setting of Barlow's disease. METHODS: Between 1999 and 2003,
      48 patients with bileaflet prolapse in the context of Barlow's disease underwent
      minimally invasive mitral valve repair using the "edge-to-edge" technique. Mean
      age was 37.9 +/- 9.1 and 58% were female. Most of the patients were in New York
      Heart Association (NYHA) class I or II and all of them had normal left
      ventricular ejection fraction. RESULTS: There were no conversions to sternotomy.
      Mean cardiopulmonary bypass and aortic cross-clamp times were 77 +/- 16 minutes
      and 56 +/- 8 minutes. No in-hospital deaths and no major postoperative
      complications occurred. At a mean follow-up of 22.7 +/- 10.6 months, survival
      rate and freedom from reoperation were 100%. All patients were in NYHA class I
      and in sinus rhythm. No residual mitral regurgitation was detected at
      echocardiography in 33 (68.7%) patients and mild insufficiency was found in 15
      (31.2%). The degree of satisfaction in terms of cosmesis and postoperative pain
      was very high and 73% of the patients were back to work and to normal activity in
      4 weeks. CONCLUSIONS: Mitral insufficiency due to Barlow's disease can be
      effectively corrected through a minimally invasive approach by using the "edge-to
      edge" technique. In our opinion, the excellent midterm results and the high
      degree of patients satisfaction certainly justify the adoption of this strategy
      in a selected group of young and active people.

PMID- 15854923
TI  - Anterior leaflet repair with patch augmentation for mitral regurgitation.
AB  - BACKGROUND: Anterior leaflet repair continues to pose significant operative
      challenges, particularly in patients with retracted or "short" anterior leaflets,
      due to rheumatic or radiation induced mitral valve disease. This often results in
      abandonment of repair in favor of mitral valve replacement, requiring
      anticoagulation and altering left ventricular (LV) function and geometry. This
      study examines our experience of anterior leaflet repair with patch augmentation.
      METHODS: Forty-two patients underwent mitral valve repair for a shortened
      anterior leaflet from 1994 to 2003. Twenty-two patients with a mean age of 53 +/-
      6 years had radiation valvulitis (XR) whereas 20 patients, age 28 +/- 7 years had
      rheumatic heart disease (RHD). Those patients with XR had a mean New York Heart
      Association (NYHA) class of 3.2 +/- 0.4 and an angina score of 2.1 +/- 0.6
      compared with a NYHA class 3.8 +/- 0.2 and no angina in RHD patients. All
      patients presented with severe MR. Anterior leaflet augmentation with a
      gluteraldehyde-treated, autologous pericardial patch and complete annuloplasty
      ring was used in all patients. Additionally, extensive subvalvar debridement was
      performed in RHD patients. Twelve XR patients underwent concomitant CABG with a
      mean of 2.4 +/- 0.8 grafts/patient. Additional surgical procedures included
      tricuspid valve repair, anterior septal defect, and aortic valve replacement.
      Mean follow-up was 39 +/- 10 months for XR patients and 12 +/- 25 months for RHD
      patients. RESULTS: There were two late deaths in XR patients from underlying
      malignancies and no deaths in RHD patients. Two RHD patients required reoperation
      for recurrent mitral regurgitation at 3 and 20 months. All patients demonstrated
      clinical improvements (NYHA I-II) following repair. No mitral stenosis was
      induced. CONCLUSIONS: Despite anterior leaflet shortening from XR or rheumatic
      alterations, opportunity still exists for gratifying mitral valve repair. By
      utilizing anterior leaflet patch augmentation, concomitantly with ring
      annuloplasty, anticoagulation is avoided, LV geometry is preserved, and follow-up
      reveals excellent functional improvement.

PMID- 15854924
TI  - Endocardial radiofrequency ablation during mitral valve surgery: effect on
      cardiac rhythm, atrial size, and function.
AB  - BACKGROUND: Restoration of sinus rhythm is thought to lead to a reduction in left
      atrial size and to recovery of atrial contraction. We aimed to investigate
      changes in atrial size and function in patients undergoing radiofrequency
      ablation for atrial fibrillation during mitral valve surgery. METHODS: In a
      prospective study, 70 patients (64 +/- 10 years) with mitral valve disease and
      atrial fibrillation underwent mitral surgery and left atrial endocardial
      radiofrequency ablation. Evaluation was achieved before surgery, at 7 days, 5
      months, and 22 months after surgery. Maximal right and left atrial areas, left
      atrial diameter, and volume were measured. Atrial filling fraction (ventricular
      filling related to atrial contraction to total ventricular filling ratio) was
      used as an index of atrial contraction. RESULTS: At the end of follow-up (22 +/-
      10 months) most patients (91%) were in sinus rhythm. Actuarial freedom from
      atrial fibrillation recurrence was 62.5% after 2 years. Atrial size decreased,
      with a significant improvement in right (36 +/- 15 vs 10 +/- 20% preoperatively,
      p < 0.0001) and left (25 +/- 12 vs 7 +/- 14%, p < 0.0001) atrial filling
      fraction. Despite similar preoperative atrial size, at the end of follow-up
      atrial fibrillation recurrence was associated with a higher left atrial volume
      than in patients free of recurrence (41 +/- 14 vs 32 +/- 9 mL/m2, p = 0.004).
      Independent predictors of atrial fibrillation recurrence were previous mitral
      procedure (p = 0.029), left ventricular ejection fraction (p = 0.033), and mitral
      rheumatic lesion (p = 0.034). CONCLUSIONS: Left atrial radiofrequency ablation
      for atrial fibrillation during mitral surgery is an effective procedure restoring
      sinus rhythm. Right and left atrial size was significantly reduced, with a
      recovery in atrial contraction.

PMID- 15854925
TI  - Surgical treatment of ascending aortic aneurysms in patients with giant cell
      aortitis.
AB  - BACKGROUND: Giant cell aortitis is a rare cause of ascending aortic aneurysm
      disease despite giant cell arteritis being a common cause of vasculitis. We
      evaluated an 8-year experience with surgical repair with regard to preoperative
      variables, extent of disease, required surgical procedures, and the propensity to
      develop additional great vessel aneurysms. METHODS: Thirty-seven patients (29
      female, 8 male; aged 69.6 +/- 9.5 years) were operated on from 1995 to 2002. Ten
      (27%) patients had a history of steroid treatment for temporal arteritis or
      polymyalgia rheumatica 8.9 +/- 3.9 years before. Nineteen (51%) patients had +3
      or +4 aortic regurgitation. Maximal aneurysm size was 6.1 +/- 0.8 cm. Thirty
      (81%) patients underwent polyethylene terephthalate fiber (Dacron) tube graft
      replacement of the ascending aorta, 4 (11%) had a modified Bentall procedure, 2
      (5%) had a valve-sparing aortic root reconstruction, and 1 (3%) had aortorrhaphy.
      Twenty-two (59%) patients required 22 +/- 9 minutes of hypothermic circulatory
      arrest for hemiarch or complete aortic arch replacement. Twenty-six (70%)
      patients had concomitant cardiac procedures. RESULTS: There was no early
      mortality. Morbidity was reexploration for bleeding in 3 (8%) patients, stroke in
      3 (8%), left vocal cord paralysis in 2 (5%), renal failure in 2 (5%), and
      gastrointestinal bleeding in 1 (3%). Mean follow-up was 2.8 +/- 2.3 years. Four
      year actuarial survival was 74% (95% confidence interval, 57% to 94%). Other
      descending or abdominal aortic or great vessel aneurysms occurred in 17 (46%)
      patients. Four patients had prior aneurysm surgery, 8 are monitored with
      aneurysms, and 5 underwent repair of an aneurysm in the follow-up period. Of 8
      late deaths, 3 were caused by complications of a descending thoracic aneurysm. No
      patient required replacement of a native aortic valve that was preserved during
      the initial operative procedure. CONCLUSIONS: Ascending aortic aneurysms caused
      by giant cell aortitis can involve the aorta from the aortic root through the
      aortic arch, thus requiring a tailored operative approach. The aortic valve
      tissue is spared from the pathologic process. Other aneurysms of the aorta and
      great vessels occur in nearly half of patients. Frequent surveillance of the
      remaining aorta is mandatory.

PMID- 15854926
TI  - Pathologic characteristics and surgical indications of superacute type A
      intramural hematoma.
AB  - BACKGROUND: The treatment policy for acute intramural hematoma involving the
      ascending aorta remains controversial. METHODS: This study compared the
      pathologic characteristics of intramural hematoma with those of acute aortic
      dissection with a false lumen. The study group comprised 69 patients with
      intramural hematoma and 156 with acute aortic dissection who underwent emergency
      operation between 1995 and 2003. RESULTS: Patients were significantly older in
      the intramural hematoma group than in the dissection group (67.7 +/- 7.2 years
      compared with 59.8 +/- 11.6 years; p < 0.0001). Pericardial hemorrhage was
      present in a higher proportion of patients in the intramural hematoma group than
      in the dissection group (66.7% compared with 50.6%; p = 0.0257). Three patients
      (4.3%) died in the intramural hematoma group, whereas 26 patients (16.7%) died in
      the dissection group (p = 0.011). Histopathologic examination showed no
      difference in the severity of medial changes, but the site of dissection
      differed. The thickness of the residual media of the adventitia side was 0.21 +/-
      0.12 mm in the intramural hematoma group compared with 0.32 +/- 0.22 mm in the
      acute aortic dissection group. Dissection was significantly nearer the adventitia
      in the intramural hematoma group (p = 0.0016). CONCLUSIONS: Dissection is nearer
      the adventitia in intramural hematoma than in dissection, leading to a greater
      probability of rupture. These results suggest that operation as soon as possible
      after the onset of intramural hematoma will contribute to improved survival.

PMID- 15854927
TI  - Release of glutaraldehyde from an albumin-glutaraldehyde tissue adhesive causes
      significant in vitro and in vivo toxicity.
AB  - BACKGROUND: A two-component sealant composed of bovine serum albumin and
      glutaraldehyde (BioGlue) is used to treat aortic dissections. Although
      glutaraldehyde guarantees strong adherence to tissues and synthetic materials,
      its toxic potential should be considered. The aim of this study was to determine
      the amount of glutaraldehyde released from BioGlue, its cytotoxic effects on
      cultured cells, and the local reaction of lung, liver, and aortic tissues to
      BioGlue. METHODS: BioGlue was prepared according to the product insert, allowed
      to polymerize, and then overlaid with saline solution. The supernatant was
      analyzed for its content of glutaraldehyde. The cytotoxic effect of BioGlue was
      evaluated by adding the supernatants to either cultured human embryo fibroblasts
      (MRC5) or mouse myoblasts (C2C12). In vivo toxicity was assessed on three
      different tissues by applying BioGlue onto a partial lung resection, a liver
      abrasion, or an intact abdominal aorta in rabbits. Tissue samples were
      histologically evaluated 2 and 7 days after application. RESULTS: Saline
      supernatants from polymerized BioGlue contained 100 to 200 mug/mL glutaraldehyde
      and were cytotoxic to both cell lines tested. Application of BioGlue to lung and
      liver tissue evoked serious adverse effects consisting of high-grade
      inflammation, edema, and toxic necrosis. Intact aortic tissue showed only low
      grade or medium-grade inflammation. CONCLUSIONS: Polymerized BioGlue releases
      amounts of glutaraldehyde that are capable of inducing cytotoxic effects both in
      vitro and in vivo. Use of BioGlue should be restricted to the aortic dissection
      procedure, as other tissues are sensitive to the amounts of glutaraldehyde
      released from the glue.

PMID- 15854929
TI  - C-reactive protein is a risk indicator for atrial fibrillation after myocardial
      revascularization.
AB  - BACKGROUND: Activation of the complement system after coronary artery bypass
      graft surgery involves C-reactive protein (CRP). This inflammatory response is
      related to baseline CRP levels and associated with postoperative arrhythmia, in
      particular atrial fibrillation (AF). We investigated whether baseline CRP levels
      are a risk indicator for the occurrence of AF and whether this phenomenon is
      cardiopulmonary bypass dependent. METHODS: C-reactive protein was measured in
      perioperative blood samples of patients of the Octopus Study (coronary artery
      bypass graft surgery with [n = 73] or without cardiopulmonary bypass [n = 79]).
      Baseline CRP was dichotomized into a low and a high baseline group, using a
      cutoff value of 3.0 mg/L. RESULTS: After coronary artery bypass graft surgery
      with cardiopulmonary bypass 11 of 53 patients (21%) with low preoperative CRP
      levels had AF versus 11 of 20 patients (55%) with high baseline CRP levels (p =
      0.01). In the off-pump group AF occurred in 4 of 52 patients (8%) who had low
      baseline CRP levels, versus 8 of 27 patients (30%) with high preoperative CRP
      levels (p = 0.002). After adjusting for age, the odds ratio (95% confidence
      interval) was 4.6 (1.4 to 15.3) with cardiopulmonary bypass, 3.7 (0.93 to 14.7)
      in the off-pump group, and 3.3 (1.4 to 7.6) for both groups together. Continuous
      baseline CRP was an independent predictor for AF in a multivariate logistic
      regression model (p = 0.02). CONCLUSIONS: Patients with high baseline CRP levels
      are at higher risk of having postoperative AF in both on-pump and off-pump
      surgery.

PMID- 15854930
TI  - Minimally invasive left ventricular epicardial lead placement: surgical
      techniques for heart failure resynchronization therapy.
AB  - BACKGROUND: Epicardial lead placement for biventricular pacing is often a rescue
      procedure after failed coronary sinus cannulation. This study aims to determine
      perioperative and early postoperative outcome of minimally invasive left
      ventricular lead placement as a management strategy for heart failure, comparing
      minithoracotomy and endoscopic approaches. METHODS: From October 2002 through
      October 2003, 41 patients underwent minimally invasive left ventricular lead
      placement, 23 (56%) by minithoracotomy and 18 (44%) endoscopically. Thirty-one
      (76%) were males, 19 (46%) had previous cardiac surgery, 21 (51%) had ischemic
      cardiomyopathy, 17 (41%) were in New York Heart Association class III or IV, and
      28 (65%) had implantable cardioverter-defibrillators. RESULTS: There were no in
      hospital deaths, intraoperative complications, or failures to implant the left
      ventricular lead. Median operative time was longer for the endoscopic approach
      (188 minutes) than for minithoracotomy (151 minutes; p = 0.006). Preoperatively,
      the endoscopic group had more mitral regurgitation (median, 2.5 versus 1.0,
      respectively; p = 0.009). QRS duration was shorter postoperatively (mean change
      from preoperative, -32 +/- 24 ms; p < 0.0001); this change was unrelated to
      surgical approach. Impedance also was less postoperatively (mean change, -490 +/-
      300 ohms; p < 0.0001), and the change was unrelated to surgical approach. Changes
      were greater the larger their preoperative values (p < 0.0001). Threshold
      increased with follow-up time (adjusted p < 0.0001), but impedance decreased
      (adjusted p = 0.0009); these trends were similar for both approaches. No changes
      were evident in left ventricular dimensions. CONCLUSIONS: Minimally invasive left
      ventricular epicardial lead placement is safe and effective, offering selection
      of the best pacing site with minimal morbidity; it can be considered a primary
      option for resynchronization therapy.

PMID- 15854931
TI  - Aprotinin inhibits protease-dependent platelet aggregation and thrombosis.
AB  - BACKGROUND: Hemostatic effects of the protease inhibitor aprotinin in cardiac
      surgery are well described, and recent evidence suggests an antithrombotic
      mechanism of aprotinin through inhibition of thrombin-mediated platelet
      activation. We hypothesized that aprotinin provides hemostasis while reducing
      vascular thrombosis by attenuating protease-dependent platelet function. METHODS:
      Rabbits (3 to 4 kg) underwent carotid artery thrombosis induced by electrical
      current. Treatment animals (n = 8) received aprotinin by a 100,000-KIU bolus
      followed by a continuous infusion (25,000 KIU/h). Control animals (n = 8)
      received crystalloid solution. Thrombus weight and time to thrombotic occlusion
      were determined. Platelet aggregation was examined in response to protease
      dependent (thrombin) and protease-independent (adenosine diphosphate, ADP)
      platelet agonists. Platelet thrombin protease-activated receptor (PAR) expression
      was analyzed by Western blot. Ear bleeding time and abdominal incisional bleeding
      were measured at baseline and serially. RESULTS: Thrombus weight was decreased by
      aprotinin (6.1 +/- 1.1 mg versus 10.8 +/- 1.5 mg, aprotinin versus control, p <
      0.05). Time to thrombotic occlusion was prolonged in the aprotinin group (17.4 +/
      1.0 minutes versus 8.3 +/- 1.3 minutes, p < 0.001). Rabbit platelet expression
      of thrombin PARs was demonstrated by Western blot analysis, and was not altered
      by aprotinin therapy. Platelet aggregation due to thrombin was decreased by
      aprotinin therapy (59.2% +/- 3.0% versus 95.8% +/- 1.5%, p < 0.001), whereas
      protease-independent, ADP-induced platelet aggregation was unchanged with
      aprotinin. Incisional bleeding was not different between groups. In the aprotinin
      group, bleeding time was unchanged at baseline and then reduced for the duration
      of the experiment (35.0 +/- 4.7 seconds versus 76.8 +/- 6.4 seconds, p < 0.05).
      CONCLUSIONS: While providing hemostatic effects, aprotinin attenuates vascular
      thrombosis in part by inhibition of PAR activation, resulting in the prevention
      of thrombin-induced platelet aggregation.

PMID- 15854932
TI  - Cardiac surgery in patients with liver cirrhosis.
AB  - BACKGROUND: Cardiac surgery was infrequently performed in patients with liver
      cirrhosis, and its clinical outcome has been reported only in small series. We
      sought to evaluate the clinical outcome of cardiac operation in patients with
      noncardiac liver cirrhosis. METHODS: Data were collected by a retrospective case
      note review. The preoperative, intraoperative, and postoperative variables were
      recorded. The severity of liver cirrhosis was graded using the Child-Pugh
      classification. RESULTS: Between January 1993 and May 2004, 18 patients with
      liver cirrhosis underwent cardiac surgery at the authors' hospital. Thirteen
      patients had hepatitis virus infection, and 5 cases were alcohol related.
      Thirteen patients were classified as Child A cirrhosis, 4 were class B, and 1 was
      class C. Sixteen patients underwent cardiac surgery with the use of
      cardiopulmonary bypass, and 2 patients underwent off-pump coronary artery bypass
      surgery. The overall in-hospital mortality rate was 6% (1 of 18), and there was
      no death in 5 class B and C cirrhotic patients. The rate of major complication
      was 39% in class A and 80% in class B and C. CONCLUSIONS: Although the
      postoperative complication was common, cardiac operation could be performed
      safely in patients with mild and advanced liver cirrhosis.

PMID- 15854933
TI  - Daily assessment of organ dysfunction and survival in intensive care unit cardiac
      surgical patients.
AB  - BACKGROUND: The purpose of this study was to develop a specific postoperative
      score for intensive care unit (ICU) cardiac surgical patients for assessment of
      organ dysfunction and survival. METHODS: This prospective study consisted of all
      consecutive adult patients admitted after cardiac surgery to our ICU over a
      period of 3 years. Evaluation of variables was performed using the first year
      patients who stayed in the ICU for at least 24 hours. The reproducibility was
      then tested in two validation sets using all patients. Performance was assessed
      with the Hosmer-Lemeshow (chi2 statistics) goodness-of-fit test and receiver
      operating characteristic (ROC) curves and compared with the Acute Physiology and
      Chronic Health Evaluation (APACHE II) and Multiple Organ Dysfunction Score
      (MODS). RESULTS: A total of 3,230 patients were admitted to the ICU after cardiac
      surgery. Mean chi2 values for the new score were 5.8 (APACHE II, 11.3; MODS, 9.7)
      for the construction set, 7.2 (APACHE II, 8.0; MODS, 4.5) for the validation set
      I, and 5.9 for the validation set II. The mean area under the ROC curve was 0.91
      (APACHE II, 0.86; MODS, 0.84) for the new score in the construction set, 0.88
      (APACHE II, 0.84; MODS, 0.84) in the validation set I, and 0.92 in the validation
      set II. CONCLUSIONS: Our new 10-variable risk index performs very well, with
      calibration and discrimination very high, better than general severity systems;
      and it is an appropriate tool for daily risk stratification in ICU cardiac
      surgery patients. Thus, it may serve as an "expert system" for diagnosing organ
      failure, decision making, resource evaluation, and predicting mortality among ICU
      cardiac surgical patients.

PMID- 15854934
TI  - Late outcome after stenting or coronary artery bypass surgery for the treatment
      of multivessel disease: a single-center matched-propensity controlled cohort
      study.
AB  - BACKGROUND: Although several randomized controlled trials examined the relative
      benefits of coronary artery bypass graft (CABG) surgery and percutaneous coronary
      intervention (PCI), the most appropriate treatment remains a matter of debate, at
      least in some subsets of patients. Therefore, we evaluated the 8-year outcome
      after multivessel stent implantation (stent group) or coronary artery bypass
      surgery (CABG group) in a single-center propensity-matched cohort study. METHODS:
      The stent study population consisted of all 409 consecutive patients who
      underwent an elective coronary intervention between 1995 and 1999 in whom at
      least 2 stents were implanted in multiple vessels. They were matched by using the
      propensity score method with 409 CABG patients of 1,723 CABG patients with
      multivessel disease who underwent elective CABG in the same period of time. The
      two populations were very different before matching. After matching, the CABG
      population resembled a stent population. RESULTS: The cumulative survival rates
      after stent were 93%, 90%, and 82% at, respectively, 3, 5, and 8 years; and after
      CABG 97%, 93%, and 87% (p = 0.02). This was caused mainly by patients with left
      main disease (p = 0.03). Event-free survival was only 70%, 68%, and 64% after
      stent and 89%, 82%, and 78% after CABG at, respectively, 3, 5, and 8 years (p <
      0.0001). After adjusting, stent was an independent predictor of higher mortality.
      CONCLUSIONS: In this matched cohort study with an 8-year follow-up, survival was
      better and less repeat revascularizations were needed among patients undergoing
      elective CABG for the treatment of multivessel disease as compared with the stent
      group.

PMID- 15854935
TI  - Effect of risk-adjusted diabetes on mortality and morbidity after coronary artery
      bypass surgery.
AB  - BACKGROUND: Diabetes is commonly regarded as a risk factor for mortality and
      morbidity after coronary artery bypass surgery. METHODS: Between April 1997 and
      December 2002, 6,033 consecutive patients underwent isolated coronary artery
      bypass surgery. Eight hundred and fourteen (13.5%) patients had diabetes (530
      oral-dependent, 284 insulin-dependent). Patients with diet-controlled diabetes
      were classified as nondiabetics. Deaths occurring over time were described using
      Kaplan-Meier techniques. To control for differences in patient characteristics,
      we constructed a propensity score (for diabetes) and this was included along with
      the comparison variable in multivariate logistic regression and Cox proportional
      hazards analyses. RESULTS: In-hospital mortality was significantly higher for
      diabetic patients in the univariate analyses; however, this association
      disappeared after adjusting for the propensity score. Further analyses found that
      insulin-dependent diabetes was associated with an increased incidence of acute
      renal failure (adjusted odds ratio 4.15; p = 0.002), deep sternal wound infection
      (adjusted odds ratio 2.96; p = 0.039), and prolonged postoperative stay (adjusted
      odds ratio 1.60; p = 0.017). Oral-controlled diabetes was not associated with any
      of these outcomes. Four hundred and ninety-eight (8.3%) deaths occurred during
      the study follow-up. After adjusting for patient characteristics, the adjusted
      hazard ratio of midterm mortality for diabetes was 1.35; p = 0.013. CONCLUSIONS:
      Insulin-dependent diabetes has a significant impact on in-hospital morbidity.
      Although diabetic patients are not at increased risk of in-hospital mortality,
      longevity is significantly decreased during a five-year follow-up period.

PMID- 15854936
TI  - Functional renal outcome in on-pump and off-pump coronary revascularization: a
      propensity-based analysis.
AB  - BACKGROUND: Since the advent of off-pump coronary artery bypass grafting (OPCAB),
      comparisons have been made between it and on-pump coronary artery bypass
      grafting. Some observe a lesser incidence of acute renal failure requiring renal
      replacement therapy with OPCAB whereas others do not. The objective was to
      compare the occurrence of renal adverse outcome between on-pump coronary artery
      bypass grafting and OPCAB. Renal adverse outcome was defined as minor (20%
      increase in serum creatinine from preoperative) or major (composite end point of
      postoperative serum creatinine >200 mumol/L or postoperative mechanical renal
      support). METHODS: The study was based on 2,041 patients with no known
      preoperative renal disease having first-time isolated coronary artery bypass
      grafting of multiple coronary arteries between January 2001 and November 2003, at
      St. Mary's Hospital, Harefield Hospital, and Hammersmith Hospital, in West
      London; 1,224 patients had on-pump coronary artery bypass grafting and 817
      patients had OPCAB. Selection bias for surgical technique was addressed by
      calculating the propensity score for each patient and using it as an independent
      variable for adjustment in the multivariate analysis. Univariate and multivariate
      ordered logistic regressions were used to identify factors associated with renal
      adverse outcome ordered as none, minor, and major. RESULTS: The number of grafts
      was 3.22 +/- 0.82 for the on-pump coronary artery bypass grafting group and 3.35
      +/- 0.95 for the OPCAB group. On-pump coronary artery bypass grafting and
      increasing age were found to be the strongest independent predictors (p < 0.001)
      of renal adverse outcome. Other independent predictors included hypertension (p =
      0.005), diabetes (p = 0.032), and preoperative serum creatinine (p = 0.001). A
      left ventricular ejection fraction of 0.30 to 0.49 (p = 0.099) and an ejection
      fraction of 0.50 or greater (p < 0.001) were associated with decreased risk
      compared with patients with an ejection fraction of less than 0.30.
      Interestingly, the use of non-left internal mammary arterial conduits
      significantly decreased the likelihood of renal adverse outcome (p = 0.034).
      CONCLUSIONS: The results of this propensity-based study show that the OPCAB
      technique may reduce the risk for minor and major renal adverse outcome after
      coronary artery bypass grafting.

PMID- 15854937
TI  - Patient-reported outcome after randomization to on-pump versus off-pump coronary
      artery surgery.
AB  - BACKGROUND: Clinical experience with off-pump coronary artery bypass surgery
      raises the question of a patient experienced benefit compared with on-pump
      surgery. This prospective and randomized study compared patient-reported outcome
      between surgical groups, as change scores at 3 months after surgery and
      longitudinally as time-averaged change from baseline through the first year after
      surgery. METHODS: In all, 120 patients were randomly assigned to on- or off-pump
      coronary artery surgery. A questionnaire for patient self-report of angina
      (Canadian Cardiovascular Society scale), health status (Short Form 36, sleep and
      sexual difficulty), and overall quality of life (Quality of Life Scale) was
      administered at baseline and at 3, 6, and 12 months after surgery. RESULTS:
      Patient groups were comparable with regard to age, symptoms, comorbidity, and
      surgical characteristics. Both groups experienced a median of two classes relief
      of angina at 3 months (p < 0.0005), maintained throughout follow-up. Paired t
      tests revealed significant improvement on all Short Form 36 subscales at 3 months
      after surgery, with the exception of physical role functioning in the on-pump
      group. No independent main effects of surgical group were observed in the between
      groups covariance models. The longitudinal effect of sex was significant in four
      Short Form 36 subscales: physical functioning, bodily pain, and role limitation
      due to physical or emotional problems. Overall quality of life scores were stable
      in both groups. CONCLUSIONS: Both on-pump and off-pump patients reported less
      angina and improved health status after surgery. There were no significant
      differences between surgical groups in health status or overall quality of life,
      neither cross-sectionally nor longitudinally.

PMID- 15854938
TI  - Robotic assisted multivessel minimally invasive direct coronary artery bypass
      with port-access stabilization and cardiac positioning: paving the way for
      outpatient coronary surgery?
AB  - BACKGROUND: Minimimal access multivessel coronary artery bypass grafting with
      same day hospital discharge remains the ultimate goal. We evaluated the
      feasibility for achieving multivessel coronary bypass through minimal access.
      METHODS: From January to July 2003, 30 patients under went off-pump minimally
      invasive multivessel coronary bypass. Internal mammary arteries were harvested
      with robotic telemanipulation with three ports. A 2-inch to 3-inch incision with
      soft tissue retractor was used to perform coronary anastomosis. Robotic ports
      were used to introduce stabilization and cardiac positioning devices. Endoscopic
      harvesting of radial artery was done when necessary. RESULTS: Twenty-three
      patients (77%) had anterior throracotomy approach and 7 (23%) had transabdominal
      approach. Average number of bypass grafts was 2.6 (range 2-4). There was no
      mortality in hospital or on 30-day follow-up. Twenty-nine patients (97%) were
      extubated on the operating table. Two patients required reoperation for bleeding
      and 1 of those patients needed conversion to sternotomy for additional bypass
      grafting. Within 24 hours of surgery 50% of patients (n = 15) were discharged,
      10% (n = 3) were discharged in 24 to 36 hours, 17% (n = 5) were discharged in 36
      to 48 hours, 17% (n = 5) were discharged in 48 to 72 hours, and 2 patients stayed
      more than 3 days in the hospital. Two patients needed readmission to hospital
      within 30 days; 1 for pleural effusion and 1 for wound infection. CONCLUSIONS:
      Robotic harvesting of internal mammary arteries and port access stabilization and
      cardiac positioning allows multivessel coronary bypass to be performed through a
      small incision. Currently, the majority of the patients can be safely discharged
      within 36 hours of operation.

PMID- 15854939
TI  - Brain injury and neuropsychological outcome after coronary artery surgery are
      affected by complement activation.
AB  - BACKGROUND: The impact of the postoperative inflammatory response on the central
      nervous system after cardiac surgery is uncertain. The goal of the study was to
      evaluate the role of complement activation on cellular brain injury in patients
      undergoing coronary artery bypass grafting. In addition, neuropsychological
      functioning was assessed. METHODS: We randomly assigned 30 patients to undergo
      surgery using either standard noncoated or heparin-coated extracorporeal
      circuits. Closed cardiopulmonary bypass and controlled suctions of pericardial
      shed blood were standardized in both groups. Complement activation and cellular
      brain injury were assessed by measuring sC5b-9 and protein s100beta.
      Neuropsychometric tests were performed at least 2 weeks before operation and at
      discharge. They served to calculate z scores of cognitive domains and changes in
      neuropsychological functioning. RESULTS: Peak value of sC5b-9 at the end of
      cardiopulmonary bypass in the noncoated group was significantly higher than in
      the heparin-coated group (p = 0.005). Changes in the heparin-coated group were
      not significant. Glial injury started after initiation of surgery and peaked at
      the end of cardiopulmonary bypass with significantly higher concentration of
      s100beta in the noncoated than in the heparin-coated group (p = 0.008). Values of
      s100beta and of sC5b-9 were significantly correlated (p = 0.03). Although no
      statistically significant between group difference was detected, z scores of
      attention and flexibility or executive functions were lowered postoperatively
      within the noncoated group (p = 0.033 and p = 0.028), whereas z scores were
      unchanged within the heparin-coated group. CONCLUSIONS: Inhibition of complement
      activation by heparin-coated cardiopulmonary bypass reduced brain cell injury and
      was associated with preserved neuropsychological functioning after coronary
      artery bypass grafting.

PMID- 15854940
TI  - Gastroepiploic artery minimally invasive grafting in reoperative patients with
      patent mammaries.
AB  - BACKGROUND: Patients with patent grafted bilateral internal thoracic arteries may
      require repeat myocardial revascularization because of either progression of
      disease in a nongrafted native vessel or failure of a saphenous vein graft. In
      order to avoid extensive dissection and possible damage of the internal thoracic
      arteries, we elected to proceed with an off-pump minimally invasive direct
      coronary artery bypass grafting (MIDCABG) approach using the pedicled right
      gastroepiploic artery. This paper summarizes our midterm angiographic results.
      METHODS: From 1996 to 2003, 15 patients were reoperated on using this approach in
      our department. Internal thoracic artery grafts always revascularized the
      anterior and lateral territories and were angiographically patent. Indications
      for repeated surgery were: (1) coronary disease progression in 8 patients; (2)
      occlusion of the saphenous vein graft in 6 patients; and (3) anastomotic stenosis
      of a pedicled right gastroepiploic artery in 1 patient. Off-pump grafting of the
      pedicled right gastroepiploic artery was targeted at the posterior descending
      artery in 14 patients, and at the left anterior descending artery in 1 patient.
      RESULTS: Thirty-day mortality was 6.5% (1 of 15 patients). With a mean follow-up
      of 56 +/- 20 months, angina-free survival was 79%. At angiographic control (mean,
      38 months), the pedicled right gastroepiploic artery was patent in 13 patients.
      One patient had an occluded right gastroepiploic artery graft at 23 months and
      another patient showed progression of disease distal to the right gastroepiploic
      artery anastomosis at 28 months. CONCLUSIONS: Off-pump MIDCABG repeat
      revascularization with a pedicled right gastroepiploic artery is an effective
      method of revascularization for patients with patent bilateral internal thoracic
      arteries.

PMID- 15854941
TI  - Outcomes of coronary artery bypass grafting in patients with connective tissue
      diseases.
AB  - BACKGROUND: Coronary artery disease represents a significant cause of morbidity
      and mortality in patients with connective tissue disease. Few reports exist on
      the results of surgical management of coronary artery disease in these patients.
      METHODS: The medical records of patients with connective tissue diseases who
      underwent coronary artery bypass grafting at our institution between 1995 and
      2002 were reviewed for demographic data, perioperative variables, and
      postoperative complications. The results were compared with data from The Society
      of Thoracic Surgeons database. RESULTS: Forty-four patients were identified from
      a total of 5,496 cases during the study period (0.8%). There were 35 patients
      with rheumatoid arthritis, 8 with systemic lupus erythematosus, and 1 with
      scleroderma. Patients with connective tissue diseases were more likely to be
      women and use immunomodulating agents. They also had a higher incidence of
      Canadian Cardiovascular Society class IV angina, need for inotropic agents, need
      for intraaortic balloon pulsation, use of blood transfusions, and leg wound
      infections. The use of steroids or other immunomodulating agents was associated
      with increased postoperative complications. Mean follow-up was 35 months. The
      overall survival and freedom from reintervention at 3 years were 89% and 75%,
      respectively. CONCLUSIONS: Coronary artery bypass grafting is a safe treatment
      modality in patients with connective tissue diseases, with acceptable early
      results. Wound complications may be a problem in this patient population. Midterm
      results are less favorable, and reinterventions are frequently required.

PMID- 15854942
TI  - Preoperative methylene blue administration in patients at high risk for
      vasoplegic syndrome during cardiac surgery.
AB  - BACKGROUND: Angiotensin-converting enzyme inhibitors, calcium channel blockers,
      and preoperative intravenous heparin use are independent risk factors for
      vasoplegic syndrome after cardiac surgery. We prospectively studied whether
      preoperative methylene blue administration would prevent the vasoplegic syndrome
      in these high-risk patients. METHODS: One hundred patients scheduled for coronary
      artery bypass graft surgery who were at high risk for vasoplegia because they
      were preoperatively using angiotensin-converting enzyme inhibitors, calcium
      channel blockers, and heparin were randomly assigned to either receive
      preoperative methylene blue (group 1, n = 50) or not receive it (group 2,
      controls, n = 50). Methylene blue (1% solution) was administered intravenously at
      a dose of 2 mg/kg for more than 30 minutes, beginning in the intensive care unit
      1 hour before surgery. RESULTS: Although similar in terms of all demographic and
      operative variables, the two groups differed significantly in terms of vasoplegic
      syndrome incidence (0% in group 1[0 of 50] vs 26% in group 2 [13 of 50]; p <
      0.001). In 6 patients, the vasoplegic syndrome was refractory to norepinephrine.
      Four of these patients survived; the other 2 had vasoplegic syndromes that were
      refractory to aggressive vasopressor therapy, and they ultimately died of
      multiorgan failure. Stroke occurred in 1 patient. The two study groups also
      differed significantly in terms of average intensive care unit stay (1.2 +/- 0.5
      days in group 1 vs 2.1 +/- 1.2 days in group 2; p < 0.001) and average hospital
      stay (6.1 +/- 1.7 days in group 1 vs 8.4 +/- 2.0 days in group 2; p < 0.001).
      CONCLUSIONS: Our results suggest that preoperative methylene blue administration
      reduces the incidence and severity of vasoplegic syndrome in high-risk patients,
      thus ensuring adequate systemic vascular resistance in both operative and
      postoperative periods and shortening both intensive care unit and hospital stays.

PMID- 15854943
TI  - Cyclosporin A but not FK-506 protects against dopamine-induced apoptosis in the
      stunned heart.
AB  - BACKGROUND: Dopamine given at moderate doses for inotropy to postischemic hearts
      has been shown to augment myocyte apoptosis in association with elevated
      cytosolic calcium. We hypothesize that dopamine-mediated apoptosis occurs through
      calcium-induced opening of the mitochondrial permeability transition (mPT) pore.
      We also hypothesize that cyclosporin A (CSA), a calcineurin inhibitor known to
      block mPT pore opening, would prevent dopamine-induced apoptosis primarily by
      inhibiting pore opening (cyclophilin D binding). METHODS: Isolated perfused
      rabbit hearts (n = 6/group) were subjected to 30 minutes of 37 degrees C
      cardioplegic arrest followed by 120 minutes reperfusion (ischemic injury that
      produces < 3% infarct by triphenyl-tetrazolium chloride [TTC] staining). Four
      groups were studied: (1) control; (2) dopamine (10 micromol/L) postischemia
      (dopa); (3) dopamine+CSA (0.2 micromol/L) (CSA+D) group; (4) dopamine+FK-506 (0.2
      micromol/L) (FK+D) group. Left ventricular developed pressure and oxygen
      consumption were measured preischemia and postischemia. Bax, caspase-3 and
      caspase-9, and poly-ADP-ribose polymerase (PARP) activation were measured by
      Western blotting. Apoptotic nuclei were quantified by terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling (TUNEL) staining. RESULTS: Dopamine
      postischemia improved contractile function and heart rate and this was not
      affected by CSA or FK. However, TUNEL positive nuclei, Bax, caspase-3 and caspase
      9 activation, and PARP cleavage were all increased in dopa and FK+D groups, but
      not in CSA+D. CONCLUSIONS: Cyclosporin is effective in preventing dopamine
      induced apoptosis in the postischemic heart. The mechanism is likely due to
      inhibition of mPT pore opening since FK-506, a potent calcineurin inhibitor that
      does not bind to cyclophilin, did not prevent this. Low dose cyclosporin may
      prove useful to prevent dopamine-induced apoptosis resulting in long-term
      preservation of cardiac function.

PMID- 15854944
TI  - Control-released hepatocyte growth factor prevents the progression of heart
      failure in stroke-prone spontaneously hypertensive rats.
AB  - BACKGROUND: We have developed a hepatocyte growth factor (HGF)-incorporating
      gelatin hydrogel sheet (HGF sheet), which was designed to release HGF more than 2
      weeks in vivo. The present study investigated whether the HGF sheet could prevent
      the progression of heart failure in stroke-prone spontaneously hypertensive rats.
      METHODS: Stroke-prone spontaneously hypertensive rats at the age of 25 weeks
      received placement of an HGF sheet on the left ventricular free wall (HGF, n =
      10) or sham-operation (control, n = 10). All animals were followed up with
      Doppler echocardiography during the next 4 weeks and then underwent histologic
      analysis. The influence of the hydrogel sheet alone was assessed by
      echocardiography and left ventricular pressure measurements. Survival study was
      performed (each group, n = 11) at the age of 30 weeks. RESULTS: There were two
      deaths in the control group and no deaths in the HGF group during the 4 weeks.
      Fractional shortening was significantly higher, and left ventricular diastolic
      dimension was significantly smaller in the HGF than in the control group. The
      slope of the peak early diastolic filling velocity and the ratio of that slope to
      the slope of the peak filling velocity at atrial contraction were significantly
      lower in the HGF than the control group. Myocardial fibrosis was lower and
      capillary density was significantly higher in the HGF than the control group.
      Placement of the hydrogel sheet alone did not affect any cardiac function
      compared with sham operation. The survival rate at 10 weeks after the surgery was
      much higher in the HGF than the control group. CONCLUSIONS: The HGF sheet
      improves cardiac function, reverses left ventricular remodeling, and markedly
      improves survival in spontaneously hypertensive rats. These beneficial effects
      are associated with angiogenesis and reduced fibrosis in the left ventricular
      myocardium.

PMID- 15854945
TI  - Initial application in the STS congenital database of complexity adjustment to
      evaluate surgical case mix and results.
AB  - BACKGROUND: The analysis of the second harvest (1998-2001) of the Society of
      Thoracic Surgeons Congenital Heart Surgery Database included the first attempt by
      the STS to apply a complexity-adjustment method to evaluate congenital heart
      surgery results. METHODS: This data harvest represents the first STS
      multiinstitutional experience with software utilizing the international
      nomenclature and database specifications adopted by the STS and the European
      Association for Cardio-Thoracic Surgery (April 2000 Annals of Thoracic Surgery)
      and the first STS Congenital Database Report incorporating a methodology
      facilitating complexity adjustment. This methodology, allowing for complexity
      adjustment, gives each operation a basic complexity score (1.5 to 15) and level
      (1 to 4) based upon the work of the EACTS-STS Aristotle Committee, a panel of 50
      expert surgeons. The complexity scoring, based on the primary procedure (from the
      EACTS-STS International Nomenclature Procedures Short List), estimates complexity
      through three factors: mortality potential, morbidity potential, and technical
      difficulty. RESULTS: This STS harvest includes data from 16 centers reporting
      12,787 cases, with discharge mortality known for 10,246 cases. The basic
      complexity score has been applied to the outcomes analysis of these cases and a
      new equation has been proposed to evaluate one aspect of performance: Aristotle
      Performance Index = Outcome x Complexity = (Survival) x (Mean Complexity Score)
      CONCLUSIONS: The complexity analysis represents a basic complexity-adjustment
      method to evaluate surgical results. Complexity is a constant precise value for a
      given patient at a given point in time; performance varies between centers.
      Future STS congenital data harvests will incorporate a second step, the
      Comprehensive Aristotle Score, utilizing additional patient specific complexity
      modifiers to allow a more precise complexity adjustment.

PMID- 15854946
TI  - Neonates with aortic coarctation and cardiogenic shock: presentation and
      outcomes.
AB  - BACKGROUND: Some neonates with coarctation of the aorta (COA) present with
      cardiogenic shock and secondary end-organ injury. The management of this subgroup
      imposes unique challenges. We review our perioperative strategy and outcomes for
      neonates with COA who presented with cardiogenic shock. METHODS: Neonates
      (younger than 30 days) with isolated COA or COA with aortic arch hypoplasia were
      identified. Retrospective review was performed to identify and characterize
      patients who presented with cardiogenic shock, defined as impaired left
      ventricular (LV) or right ventricular (RV) systolic function, or both,
      respiratory failure requiring tracheal intubation, and metabolic acidosis.
      RESULTS: Thirteen neonates presented in cardiogenic shock and underwent surgical
      repair. No patients required catheter or surgical reintervention for
      recoarctation. There were no deaths at a mean follow-up of 54 months. Group I
      neonates (isolated COA, n = 7) underwent end-to-end anastomosis through left
      thoracotomy. The mean age and pH at presentation were 9 (+/-1.1) days and 7.07
      (+/-0.21), respectively. The mean preoperative and postoperative LV myocardial
      performance indices (MPI) were 0.81 (+/-0.22) and 0.37 (+/-0.16), respectively (p
      = 0.002). Group II neonates (COA with arch hypoplasia +/- ventricular septal
      defect, n = 6) underwent aortic arch advancement and ventricular septal defect
      closure through median sternotomy. The mean time from diagnosis to surgery in
      group II was 5.5 (+/-1.9) days versus 2.4 (+/-1.5) days in group 1 (p = 0.01).
      The mean age and pH at presentation were 11.8 (+/-9.3) days and 7.02 (+/-0.21),
      respectively. The mean preoperative and postoperative LV MPI were 0.46 (+/-0.13)
      and 0.35 (+/-0.11), respectively (p = 0.02). The total hospital length of stay in
      group II patients was 18 (+/-6.23) days versus 11.3 (+/-5. 7) days in group I (p
      = 0.04). CONCLUSIONS: Timely intervention with a strategy individualized to the
      patient anatomy can be performed with excellent outcomes in neonates with COA and
      cardiogenic shock. Neonates with isolated COA had worse preoperative LV MPI,
      which reflects more significant global left ventricular systolic dysfunction in
      this subgroup. The elapsed time from diagnosis to surgery was decreased in
      neonates with isolated COA.

PMID- 15854947
TI  - Late left pulmonary artery stenosis after the Norwood procedure is prevented by a
      modification in shunt construction.
AB  - BACKGROUND: Late left pulmonary artery (LPA) stenosis occurs commonly after the
      Norwood procedure, and complicates subsequent stages. Compression by the neoaorta
      and ductal stump may favor flow into the right pulmonary artery, resulting in LPA
      hypoplasia. We hypothesize that an early compromise of LPA flow contributes to
      late LPA stenosis, and have modified our shunt to compensate. METHODS: We
      reviewed 34 consecutive neonates undergoing the Norwood procedure between 1999
      and 2002, and morphometric data from angiograms obtained before the bidirectional
      cavopulmonary anastomosis (BDCPA). The Norwood technique included an autologous
      arch reconstruction with or without augmentation, and a polytetrafluoroethylene
      Blalock-Taussig shunt (BTS). Starting February 2001, the distal shunt was
      modified from an end-to-side construction to an oblique anastomosis directed into
      the retroaortic LPA. RESULTS: Norwood survival was 82%. LPA stenosis required
      plasty in 10 of 13 (77%) premodification survivors, and in 2 of 9 (22%)
      postmodification (p = 0.027). Bypass time was 151 +/- 65 minutes with LPA plasty
      versus 95 +/- 50 minutes without. Mortality (15% vs 0%), hospital stay (25 +/- 35
      vs 9 +/- 6 days), and incidence of subsequent interventions were correspondingly
      higher with LPA stenosis. Ten of 13 patients (77%) with a BTS insertion point
      outside the central region of the pulmonary artery required LPA plasty, versus 2
      of 9 (22%) with an insertion nearer to the center (p = 0.027). CONCLUSIONS: An
      oblique distal BTS anastomosis directed leftward onto the retroaortic pulmonary
      artery at the time of the Norwood procedure may prevent late LPA stenosis and its
      attendant morbidity.

PMID- 15854949
TI  - Is there a role for mechanical valved conduits in the pulmonary position?
AB  - BACKGROUND: The use of allografts or xenografts is the treatment of choice for
      pulmonary valve replacement. However, the limited durability is responsible for
      multiple reoperations associated with increased morbidity. In search of a
      definitive solution, the implantation of a mechanical valved conduit might be an
      option in highly selected patients. This study evaluated short-term results after
      pulmonary valve replacement with a mechanical valved conduit. METHODS: Fourteen
      patients underwent pulmonary valve replacement with a mechanical valved conduit.
      All patients had a mean of 3.0 +/- 1.2 previous operations. Seven patients were
      previously operated on for tetralogy of Fallot, 3 patients for pulmonary atresia,
      3 patients for common arterial trunk, and 1 patient for subaortic stenosis.
      RESULTS: All patients survived the operation and are currently well. At follow-up
      (11 to 63 months), all but 2 patients showed normal right ventricular function,
      with a mean gradient of 14 +/- 9 mm Hg (range, 4 to 30 mm Hg) across the
      pulmonary valve. At follow-up, there was no evidence of valve failure or tissue
      growth within the valve annulus. All patients are receiving anticoagulants to
      maintain an international normalized ratio of 3.0 to 4.5. CONCLUSIONS: In highly
      selected patients, the use of a mechanical valved conduit in the pulmonary
      position leads to satisfactory results. To avoid a predictable reoperation after
      multiple right ventricular outflow tract reconstruction, and therefore
      reoperation-related morbidity, the implantation of a mechanical prosthesis as a
      lifelong solution requires consideration. Selection criteria for this permanent
      solution should include older age, multiple previous operations, and patient
      compliance with anticoagulant therapy.

PMID- 15854951
TI  - Risk factors, dynamics, and cutoff values for homograft stenosis after the Ross
      procedure.
AB  - BACKGROUND: The purpose of this study was to find homograft-related factors that
      might be associated with the development of stenosis after the Ross procedure, as
      well as to identify the natural dynamics of stenosis and find echographic cutoff
      values after one year of follow-up that might predict such an outcome. METHODS:
      We followed up 71 patients (mean age, 24.27 +/- 16.57 years) who had such a
      procedure prospectively by transthoracic echocardiography, between 1993 and 2002.
      Follow-up was 55.26 +/- 29.63 months and was 90.14% complete. Homografts were
      harvested from heart-beating donors or cardiac transplant recipients. Allograft
      stenosis was analyzed and risk factors were identified by univariate,
      multivariate, and survival analysis methods. Stenosis was defined as a mean
      gradient greater than or equal to 20 mm Hg. RESULTS: There were two reoperations
      and 21 homografts were stenotic at the last follow-up, ten of which were already
      so at one year after the procedure. Cox regression analysis revealed a
      transhomograft gradient greater than 9 mm Hg at 1 year after the procedure
      (hazard ratio [HR] = 10.04) and homograft size (HR = 0.75) as independent
      predictors for stenosis. Stenosis-free survival was 85.94 +/- 4.35%, 75.51 +/-
      5.55%, and 68.56 +/- 6.34 after 1, 3, and 5 years, respectively. A cutoff value
      of 9 mm Hg at 1 year of follow-up could predict different stenosis-free survival
      rates. CONCLUSIONS: Homograft size is the most important homograft-related factor
      for stenosis. Most of the increase in transhomograft gradient occurs in the first
      24 months. A gradient of 9 mm Hg or more after 1 year predicts the late
      occurrence of stenosis.

PMID- 15854953
TI  - Airway obstruction owing to tracheopathia osteoplastica: treatment by linear
      tracheoplasty.
AB  - BACKGROUND: Tracheopathia osteoplastica is a rare disease that may involve the
      entire trachea and progress to critical airway obstruction. It is not dilatable
      and does not respond to laser therapy or bronchoscopic curettage. Stents usually
      cannot be inserted. METHODS: Lack of involvement of the membranous wall by the
      disease allows tracheal widening after complete linear tracheoplasty. Opening is
      preserved during healing by prolonged stenting with a T or T-Y silicone tube.
      RESULTS: Stent removal after firm healing produced long-term correction of
      stenosis in 3 of 4 patients, examined up to 12 years. CONCLUSIONS: Severe,
      symptomatic tracheal obstruction by tracheopathia osteoplastica is definitively
      surgically correctible.

PMID- 15854954
TI  - Problems in diagnosis and surgical management of clinical N1 non-small cell lung
      cancer.
AB  - BACKGROUND: Clinical diagnosis of the nodal status is a significant factor in
      determining the treatment and predicting the prognosis in lung cancer patients. A
      patient with clinical N1 (cN1) disease is usually considered to be a candidate
      for surgical intervention in the present staging system in non-small cell lung
      cancer (NSCLC). However, cN1 disease is a subset for which the method of
      treatment and surgical results are variable, simply because both upstaging and
      downstaging can occur. We evaluated the surgical and pathologic results of cN1
      NSCLC patients to reveal the problems in diagnosis and surgical management for
      this subset. METHODS: From January 1998 to March 2003, 1,606 patients underwent
      thoracotomy for primary lung cancer at the National Cancer Center Hospital. Among
      them, the subjects for this study were 168 (10.5%) NSCLC patients who were
      clinically diagnosed as having N1 disease and underwent surgery without induction
      therapy. RESULTS: The tumor cell types of these 168 cN1 NSCLC patients were
      adenocarcinoma in 73 (44%) and squamous cell carcinoma in 79 (47%). Pneumonectomy
      was performed in 26% (n = 43) patients, bilobectomy in 15% (n = 25), and
      exploratory thoracotomy in 11% (n = 19). Of 19 exploratory thoracotomy cases, 10
      cases were due to pleural dissemination. The pathologic nodal status of the 135
      patients who underwent pulmonary resection and mediastinal dissection was pN0,
      19% (n = 25); pN1, 44% (n = 59); and pN2-3, 37% (n = 51). Of the 55
      adenocarcinomas, 60% (n = 33) were revealed to be N2 disease on pathologic
      examination. There were no significant differences in the serum tumor markers
      between the pN1 and pN2 groups. Among the 25 patients who were downstaged
      postoperatively (cN1-pN0), 21 patients (84%) showed obstructive pneumonia in the
      lung. CONCLUSIONS: In the staging process of cN1 disease, it will be helpful to
      perform mediastinoscopy and thoracoscopy to avoid unnecessary thoracotomy
      especially in adenocarcinoma, even though mediastinal nodes and pleural
      dissemination were negative on computed tomography investigation. Since extensive
      pulmonary resection (bilobectomy or pneumonectomy) was required in 41% of the
      patients, preoperative detailed cardiopulmonary function tests should be
      mandatory to reduce surgical morbidity and mortality. On the other hand, when
      pneumonia due to airway obstruction by the tumor exists, false-positive hilar
      nodes can be expected.

PMID- 15854955
TI  - Surgical resection for residual N2 disease after induction chemotherapy.
AB  - BACKGROUND: Induction therapy is a common treatment modality for patients with
      stage IIIA non-small cell lung cancer (NSCLC). Although mediastinal nodal
      downstaging after induction therapy is generally considered a favorable
      prognostic feature, the benefit of resection in the presence of residual N2
      disease is controversial. In this study we analyzed our experience with resection
      after induction chemotherapy in patients with residual N2 disease to more
      precisely define the role of surgical resection in this group of patients.
      METHODS: In this retrospective analysis, we reviewed the records of 78 patients
      with N2 disease who received induction therapy with preoperative intent between
      1990 and 2003. All patients had potentially resectable disease. Survival analysis
      was performed using the Kaplan-Meier method. A Cox proportional hazards
      regression model was used to evaluate multiple prognostic factors. RESULTS: There
      were 78 patients (39 men) with a median age of 64 years. Sixty had nonsquamous
      histology. Resection was performed in 52 patients (47 R0). Hospital mortality was
      1.9%. A complete pathologic response occurred in 2 of 52 (3.8%) patients and 19
      of 52 (36%) patients had no residual N2 disease. Overall 5-year survival for
      resected patients was 23%. Overall 5-year survival was 30% for N0-N1 patients and
      19% for those with residual N2 disease. Multivariable analysis identified
      clinical response to therapy (p = 0.0007) and histology (p = 0.01), but not
      residual N2 disease (p = 0.65), as important prognostic variables. CONCLUSIONS:
      Surgical resection may be a viable option for patients with residual N2 disease
      after induction chemotherapy, provided an R0 resection can be performed.

PMID- 15854956
TI  - Resection of locally advanced (T4) non-small cell lung cancer with
      cardiopulmonary bypass.
AB  - BACKGROUND: Resection of T4 non-small cell lung cancer (NSCLC) on cardiopulmonary
      bypass (CPB) has rarely been reported in the literature. Hence, we have reviewed
      our experience in the role of CPB for the surgical treatment of locally advanced
      NSCLC. METHODS: All patients undergoing lung resection for bronchogenic carcinoma
      on CPB in our institution between January 1998 and June 2004 were reviewed.
      RESULTS: Seven patients underwent lung resections on CPB for bronchogenic
      carcinoma during the study period. Cardiopulmonary bypass was performed for
      tumors invading the subclavian artery down to the aortic arch (n = 2), the
      descending aorta (n = 1), or the origin of the left pulmonary artery with the
      left atrium (n = 2). All patients were discharged home after 9 to 21 days
      (median, 15 days). In the long term, 2 patients are alive without recurrence 17
      and 25 months after their operations, and 3 are alive with recurrence 8, 13, and
      54 months postoperatively. Two additional patients required CPB while undergoing
      carinal resection for difficulty ventilating the left lung. Both patients had a
      difficult postoperative course, but were eventually discharged from hospital. One
      patient died without recurrence 6 months later, and the other is alive without
      recurrence after 72 months. CONCLUSIONS: This study confirms the safety of CPB
      for NSCLC invading the great vessels and/or the left atrium in well-selected
      patients, and its utility when pulmonary edema develops during carinal resection.
      Further studies, however, are required to confirm long-term survival.

PMID- 15854958
TI  - Prediction rule for atrial fibrillation after major noncardiac thoracic surgery.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common complication after major
      noncardiac thoracic surgery and increases the cost and morbidity of these
      operations. We sought to derive and validate a clinical prediction rule to risk
      stratify patients for postoperative AF. METHODS: For a cohort of cancer patients
      who underwent noncardiac thoracic surgery, we examined the association of
      preoperative clinical variables with development of postoperative AF. Logistic
      regression identified multivariable predictors of AF and a clinical risk score
      was developed by assigning weighted point scores for the presence of each
      significant covariate. An independent data set was used for validation purposes.
      RESULTS: Of the 856 patients, 147 (17.2%) developed postoperative AF. Male gender
      (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1 to 2.4), advanced age (55
      to 74 years OR 4.4, 95% CI 2.0 to 9.8; > or =75 years OR 9.2, 95% CI 3.9 to
      21.5), and preoperative heart rate greater than or equal to 72 beats per minute
      (OR 1.7, 95% CI 1.2 to 2.5) were independent predictors of postoperative AF. A
      risk score was assigned with male gender and heart rate greater than or equal to
      72 beats per minute each receiving 1 point, and age 55 to 74 and greater than or
      equal to 75 years receiving 3 and 4 points, respectively. The risk of
      postoperative AF ranged from 0% (0 points) to 54.6% (6 points) (p < 0.001). The
      score-based risk in both derivation and validation sets was similar (p = 0.66).
      CONCLUSIONS: A prediction rule using clinical variables can be used to predict
      the risk of postoperative AF after noncardiac thoracic surgery. This information
      can be used to guide prophylactic therapy.

PMID- 15854959
TI  - Inflammatory gene polymorphisms influence risk of postoperative morbidity after
      lung resection.
AB  - BACKGROUND: Polymorphisms in genes encoding proteins involved in the inflammatory
      response may lead to a differential response to a noxious stimulus. We
      hypothesized that proinflammatory alleles at candidate loci would predispose
      patients undergoing lung resection to cardiopulmonary complications with a
      presumed inflammatory cause. METHODS: We determined the genotypes at six
      candidate loci in 155 patients who underwent 160 lung resection operations at our
      center. We correlated these results with data from our clinical database,
      constructed a model predicting the risk of postoperative complications, and
      assessed its adequacy using receiver operating characteristic curve methodology.
      RESULTS: Preexisting cardiovascular disease (p < 0.001), primary lung cancer (p =
      0.009), extent of lung resection (p = 0.042), interleukin 6 genotype (p = 0.017),
      and tumor necrosis factor genotype (p = 0.005) were significantly associated with
      complications. The odds ratio for complications for rare allele homozygosity was
      3.9 (95% confidence interval, 1.4 to 10.4) for interleukin 6 and 15.3 (95%
      confidence interval, 1.7 to 131.4) for tumor necrosis factor. In multivariate
      analysis we found that cardiovascular disease (p < 0.001; odds ratio, 4.0 [95%
      confidence interval, 1.9 to 8.6]), interleukin 6 genotype (p = 0.027; odds ratio,
      1.8 [95% confidence interval, 1.1 to 3.1]), and tumor necrosis factor genotype (p
      = 0.011; odds ratio, 2.5 [95% confidence interval, 1.2 to 5.1]) were
      independently predictive of complications, with an area under the receiver
      operating characteristic curve for the entire model of 0.765. CONCLUSIONS:
      Carriage of specific alleles, and homozygosity in particular, at loci within the
      interleukin 6 and tumor necrosis factor genes appears to contribute to the risk
      of experiencing an adverse event after lung resection.

PMID- 15854960
TI  - Surgery for pulmonary nodules in breast cancer patients.
AB  - BACKGROUND: The nature of pulmonary nodules that appeared in patients who had
      received surgery for breast cancer, as well as the role of surgery for such
      pulmonary nodules, remains unclear. METHODS: A total of 52 consecutive patients
      who underwent surgery for pulmonary nodules between 1992 and 2001 after curative
      operation for breast cancer were reviewed. RESULTS: The pathologic diagnoses of
      pulmonary nodules were pulmonary metastases of breast cancer in 39 patients,
      primary lung cancer in 6, and other diagnoses in 7 (tuberculosis and hamartoma in
      2 each; sclerosing hemangioma, organizing pneumonia, and paragohimiasis in 1
      each). The incidence of multiple pulmonary nodules was significantly higher in
      metastatic breast cancer patients (64.1%), but 33.3% of primary lung cancer
      patients and 28.6% of other histology patients had multiple pulmonary nodules.
      The average disease-free interval from the initial mastectomy was significantly
      shorter in metastatic breast cancer patients (66.8 months), but disease-free
      intervals were longer than 5 years in 41.0% of metastatic breast cancer patients.
      The 5-year survival rate after pulmonary metastectomy of metastatic breast cancer
      patients was 30.8%, which was not better than those documented in metastatic
      breast cancer patients treated with modern chemotherapy. There was no significant
      difference in postmetastectomy survival according to the number or sites of
      pulmonary metastases or the disease-free interval. CONCLUSIONS: Pulmonary
      metastectomy may not be the primary therapeutic option in metastatic breast
      cancer patients, and patients should be treated principally with chemotherapy. As
      pulmonary nodules that appear in breast cancer patients are not always pulmonary
      metastases, the pathologic diagnosis should be confirmed, and surgery is an
      option for the pathologic confirmation.

PMID- 15854962
TI  - Differential response to preoperative chemoradiation and surgery in esophageal
      adenocarcinomas based on presence of Barrett's esophagus and symptomatic
      gastroesophageal reflux.
AB  - BACKGROUND: Barrett's esophagus and gastroesophageal reflux disease (GERD) are
      recognized to predispose to esophageal adenocarcinoma. Abdel-Latif and colleagues
      recently suggested that esophageal adenocarcinoma patients with GERD might be
      resistant to multimodality treatment. In this study, we investigated potential
      differences in clinical outcomes in esophageal adenocarcinoma patients based on
      the presence of identifiable Barrett's mucosa and/or history of symptomatic GERD.
      METHODS: Eighty-four patients with resectable esophageal adenocarcinoma, who
      completed the planned preoperative chemoradiation and underwent a potentially
      curative esophageal resection were retrospectively evaluated. Postoperative
      survival was compared between patients with or without underlying Barrett's
      esophagus and history of symptomatic GERD. Patients with pathologic complete
      response (path CR) and those with partial or no response (path PR) were compared
      to determine if presence of Barrett's esophagus and history of symptomatic GERD
      influence the path CR rates. RESULTS: We found significantly lower postoperative
      survival in patients with Barrett's associated adenocarcinoma (vs adenocarcinoma
      arising de novo, p = 0.031) and patients with symptomatic GERD (vs patients
      without symptomatic GERD, p = 0.019). Furthermore, the subset of patients with
      path PR (vs path CR) after chemoradiation have a significantly higher proportion
      of patients with Barrett's esophagus (HR = 4.38, confidence interval [CI] = 1.39
      to 13.83, p = 0.012) and patients with GERD (HR = 2.71, CI = 1.13 to 6.50, p =
      0.026). CONCLUSIONS: Patients with esophageal adenocarcinoma may have differences
      in response to preoperative chemoradiation based on the presence of Barrett's
      esophagus and history of symptomatic GERD.

PMID- 15854963
TI  - Blood flow responses in the peristernal thoracic wall during vacuum-assisted
      closure therapy.
AB  - BACKGROUND: Vacuum-assisted closure (VAC) therapy is a recently introduced method
      for the treatment of poststernotomy mediastinitis. The aim of this study was to
      examine the effects of negative pressure on peristernal soft tissue blood flow
      and metabolism because the mechanisms by which vacuum-assisted closure therapy
      promotes wound healing are not known in detail. METHODS: Microvascular blood flow
      was examined by laser Doppler velocimetry in an uninfected porcine sternotomy
      wound model. Microvascular blood flow was examined in the muscular and
      subcutaneous tissue, at different distances from the wound edge, after the
      application of -50 to -200 mm Hg. Wound fluid pH, partial pressures of oxygen and
      carbon dioxide, bicarbonate, and lactate were analyzed after 0, 30, and 60
      minutes of continuous negative pressure. RESULTS: Vacuum-assisted closure therapy
      induced an increase in the microvascular blood flow a few centimeters from the
      wound edge. In muscular tissue, the distance from the wound edge to the position
      at which the blood flow was increased was shorter than that in subcutaneous
      tissue. Close to the wound edge, relative hypoperfusion was observed. The
      hypoperfused zone was larger at high negative pressures and was especially
      prominent in subcutaneous tissue. Wound fluid partial pressure of oxygen and
      lactate levels were increased after 60 minutes of vacuum-assisted closure
      therapy, which may be the result of changes in the microvascular blood flow.
      CONCLUSIONS: Vacuum-assisted closure therapy induces a change in microvascular
      blood flow that is dependent on the pressure applied, the distance from the wound
      edge, and the tissue type. It may be beneficial to tailor the negative pressure
      used for vacuum-assisted closure therapy according to the wound tissue
      composition. Wound fluid partial pressure of oxygen and lactate levels increased
      during vacuum-assisted closure therapy. This combination is known to promote
      wound healing.

PMID- 15854965
TI  - First clinical experience with the HEARTSTRING, a device for proximal anastomoses
      in coronary surgery.
AB  - PURPOSE: The HEARTSTRING is a device designed to enable the creation of a
      clampless hand-sewn proximal anastomosis. DESCRIPTION: Seventy-six patients who
      underwent myocardial revascularization had 113 proximal anastomoses created by
      the HEARTSTRING. Fifty-five procedures were performed on cardiopulmonary bypass
      and 21, off pump. EVALUATION: Of 114 intended proximal anastomoses, 113 (99.1%)
      were successfully performed using the HEARTSTRING. The conduits anastomosed
      proximal with support of the HEARTSTRING were in 92 cases saphenous veins and in
      21 cases radial arteries. Mean time to perform a HEARTSTRING-supported
      anastomosis was 6.6 +/- 1.2 minutes. One patient (1.3%) died postoperatively; the
      death was not device related. In 1 additional patient (1.3%), a stroke most
      likely due to air embolism occurred. Forty-nine patients (64.5%) underwent a
      predischarge coronary angiography (n = 20) or a contrast multislice computed
      tomography (n = 29). Of 76 grafts with a HEARTSTRING-supported proximal
      anastomosis, 74 (97.4%) were patent in these 49 patients. CONCLUSIONS: Our
      initial clinical experience with the HEARTSTRING demonstrates safety,
      reliability, and ease of use. Side clamping of the ascending aorta can be
      avoided, potentially decreasing the incidence of neurologic complications.

PMID- 15854967
TI  - Early clinical results with a magnetic connector for distal coronary artery
      anastomoses.
AB  - PURPOSE: The main goals in the development of an anastomotic device are to reduce
      the invasiveness of the procedure and to improve graft patency. We analyze our
      preliminary clinical experience with the Ventrica magnetic vascular positioner
      (MVP) series 6000 system. DESCRIPTION: Eighteen distal anastomoses were performed
      in 11 patients using the MVP. EVALUATION: The target artery for MVP was left
      anterior descending in 9 patients, a marginal branch in 4, the first diagonal
      branch in 3, and the right coronary artery in 2. Graft material was the left
      internal thoracic artery in 9 patients, saphenous vein in 6, the right internal
      thoracic artery in 2, and the radial artery in 1 case. Fifteen anastomoses were
      performed in an end-to-side and 3 in a side-to-side fashion. Predischarge
      angiography was performed in 10 of 11 patients. There was a patent MVP
      anastomosis in all patients. CONCLUSIONS: Distal anastomoses using the MVP were
      performed successfully in all patients. The procedure is simple. Short-term
      patency is excellent. Further randomized trials are necessary to determine long
      term safety and patency.

PMID- 15854969
TI  - Troubleshooting video-assisted thoracic surgery lobectomy.
AB  - PURPOSE: Surgeons converting their open lobectomy skills to video-assisted
      thoracic surgery (VATS) techniques have sought traditional technical courses,
      publications, and physician mentoring. While these are useful in teaching basic
      principles, it is more difficult to promulgate the numerous advanced techniques
      or technical "tricks" that deal with anatomical variations or pathologic changes
      in the lung tissue. DESCRIPTION: Engineers have simplified the process of rolling
      out complex technology by using troubleshooting guides. Accordingly, helpful
      video-assisted lobectomy maneuvers have been categorized according to the
      specific problems occasionally encountered at different points in the operation.
      EVALUATION: These maneuvers were compiled and reviewed by a panel of thoracic
      surgeons experienced in video-assisted lobectomies and have been active in
      teaching and mentoring of thoracic surgeons, residents and fellows. The
      techniques described have been used successfully by the authors to overcome
      exposure and instrumentation limitations, to achieve the outcomes reported in
      their series, and to guide trainees. CONCLUSIONS: Troubleshooting guides offer an
      organized means for surgeons to improve the parts of the video-assisted lobectomy
      procedure that they find tedious or challenging.

PMID- 15854971
TI  - Covered stent treatment of right pulmonary artery stenosis and Waterston shunt.
AB  - A 35-year-old man with residual Waterston shunt and concomitant right pulmonary
      artery stenosis after multiple surgery for tetralogy of Fallot presented with
      significant left to right shunt and left heart failure. We describe the
      percutaneous placement of an endovascular stent graft to occlude the Waterston
      shunt and relieve the right pulmonary artery stenosis simultaneously. This novel
      use of a covered stent effectively treated a residual problem without reoperative
      thoracotomy.

PMID- 15854972
TI  - Histopathologic findings in a novel decellularized pulmonary homograft: an
      autopsy study.
AB  - Innovative valved conduits for reconstruction of the right ventricular outflow
      tract are desirable to overcome the risk of valve deterioration of conventional
      homografts. This study describes the histopathology of a novel decellularized
      pulmonary homograft (SynerGraft) implanted in the right ventricular outflow tract
      of a 60-year-old man 5 weeks before death. The histomorphology of this
      decellularized homograft showed integrity of its extracellular matrix and a
      gradual cellular infiltrate consisting predominantly of macrophages, resembling
      an early nonspecific inflammatory phase of recellularization without any signs of
      a specific immunologic interference 5 weeks after implantation. Whether this
      morphologic appearance precedes the desired repopulation with autologous
      fibroblasts remains to be established.

PMID- 15854973
TI  - Aortic atresia and type B interrupted aortic arch: diagnosis by physiologic
      cerebral monitoring.
AB  - Physiologic cerebral monitoring has become an important part of our
      cardiovascular surgical unit. We recently encountered an unusual variant of
      aortic atresia that was first suggested by physiologic cerebral monitoring and
      required modification of our operative technique. We describe and discuss the
      anatomy, its translation into cerebral monitor findings, and how we modified our
      operative technique.

PMID- 15854974
TI  - Acute occlusion of left coronary ostium associated with congenital quadricuspid
      aortic valve.
AB  - A 10-year-old girl suffered from chest discomfort during exercise. She
      experienced an acute myocardial infarction accompanied by an obstruction in an
      orifice to the left coronary artery. An emergency operation revealed that the
      aortic valve was quadricuspid, and a left-sided small cusp had adhered to the
      aortic wall resulting in an unusual sac with a tiny slit. Resection of the sac
      disclosed the ostium to left coronary artery. Blood toward the left coronary
      artery passed through the tiny slit. The mechanisms of obstruction in the
      coronary artery were uncertain. She recovered well after the aortic valve
      replacement with resection of the aortic cusps.

PMID- 15854975
TI  - Surgical repair and stent positioning for type A acute aortic dissection: a step
      forward?
AB  - We report two cases of type A acute aortic dissection in which the traditional
      ascending aorta replacement was completed by aortic arch stenting to achieve a
      complete treatment and to avoid the risks that are connected to aortic arch
      replacement. Correct deployment of the stent was evaluated through an endoscope
      inserted in the transverse arch, which avoided fluoroangiography and the
      involvement of a radiologic team.

PMID- 15854976
TI  - Interventricular septal hematoma in ventricular septal defect patch closure.
AB  - We report a case of interventricular septal hematoma after patch closure of a
      perimembranous ventricular septal defect in a 4-month-old infant. On
      postoperative day 1, echocardiography showed a voluminous intramural hematoma
      causing severe thickening of the ventricular septum. Surgical revision was
      necessary immediately to drain the hematoma.

PMID- 15854977
TI  - Surgical treatment of a huge cavernous hemangioma surrounding the right coronary
      artery.
AB  - Hemangioma of the heart is an extremely rare benign cardiac tumor. A 61-year-old
      woman presented with a huge hemangioma on the right ventricle. The tumor was
      completely surrounding the right coronary artery. Under cardiopulmonary bypass,
      the right coronary artery was transected from the aortic sinus and the supplying
      arteries of the tumor were divided. The tumor was successfully resected, and the
      right coronary artery was reanastomosed to the aortic sinus.

PMID- 15854978
TI  - Deep hypothermia and circulatory arrest for surgery of high extracranial internal
      carotid aneurysm.
AB  - A large, high internal carotid artery aneurysm partially filled with thrombi in a
      young, 26-year-old male patient was treated by bypass grafting under deep
      hypothermia and circulatory arrest. This approach may be preferable to other
      alternatives in patients with high embolic risk and difficult exposure or
      inadequate space for distal carotid artery clamping.

PMID- 15854979
TI  - Avoidable errors in cardiac surgery: anastomosis of the left internal mammary
      artery to a vein.
AB  - We report the case of a patient who had undergone a three-vessel coronary artery
      bypass graft surgery 6 years earlier, during which the left internal mammary
      artery was erroneously anastomosed to an epicardial vein instead of the intended
      target, an intramyocardial left anterior descending artery. Visually
      distinguishing artery from vein can be occasionally challenging and can lead to
      errors in distal anastomosis. This case report identifies two difficult problems
      in cardiac surgery and discusses the techniques to differentiate between arterial
      and venous targets.

PMID- 15854980
TI  - Growth of a left atrial sarcoma followed by resection and autotransplantation.
AB  - Left atrial sarcomas are among the rarest primary cardiac tumors. This type of
      tumor has an aggressive behavior and is often resistant to standard approaches to
      treatment. In this case report we show its rapid growth in vivo and document
      successful local control with an aggressive surgical approach of ex-vivo
      resection, reconstruction of the left atrium by a pericardial patch, and
      subsequent autotransplantation.

PMID- 15854981
TI  - Therapeutic management of broncholithiasis.
AB  - Broncholithiasis is characterized by calcified perihilar and mediastinal lymph
      nodes eroding into the tracheobronchial tree. We report herein 4 cases of
      symptomatic broncholithiasis managed by surgical resection in 2 cases and
      bronchoscopic removal in 2 cases. From our experience and from the literature
      review, bronchoscopic removal should be considered in cases of uncomplicated and
      loose broncholithiasis, whereas surgical management should be chosen first in
      complicated cases such as obstructive pneumonitis, bronchiectasis, massive
      hemoptysis, and bronchoesophageal fistulas.

PMID- 15854982
TI  - Congenital bronchoesophageal fistula in a patient with Crohn's disease: a
      cautionary tale.
AB  - We present the case of a young lady suffering from Crohn's disease who was
      diagnosed as having a disabling bronchoesophageal fistula. This was mistakenly
      thought to be due to the Crohn's disease, and surgery was declined for fear of
      further complications. She required multiple admissions for frequent chest
      infections. At review, 5 years later for a second opinion, the fistula was deemed
      congenital in origin. The fistula was successfully resected, and the histology
      confirmed the diagnosis.

PMID- 15854983
TI  - Left pneumonectomy for lung cancer after correction of contralateral partial
      anomalous pulmonary venous return.
AB  - We report the successful treatment of a 48-year-old man with left lung cancer and
      contralateral partial anomalous pulmonary venous return (PAPVR). He was found to
      have an abnormal shadow on a regular checkup. Sputum cytology revealed squamous
      cell carcinoma. Chest computed tomography showed not only a left hilar mass but
      also showed that his right superior pulmonary vein was draining into the high
      portion of the superior vena cava. In the presence of the right partial anomalous
      pulmonary venous return, it was believed that left pneumonectomy would cause
      serious postoperative heart failure due to an increase in the left-to-right
      shunt. Therefore his partial anomalous pulmonary venous return was corrected
      first under cardiopulmonary bypass, and 3 weeks later he underwent successful
      radical left pneumonectomy.

PMID- 15854984
TI  - Videopericardioscopy using endothoracic sonography for lung cancer staging.
AB  - We performed videopericardioscopy using an endothoracic sonographic probe for the
      staging of left hilar nonsmall cell lung cancer. This method will be useful for
      an accurate diagnosis of direct tumor invasion into the intrapericardial great
      vessels and lead to the institution of appropriate treatment.

PMID- 15854985
TI  - Iris metastasis of esophageal cancer.
AB  - Ocular metastasis in patients with esophageal cancer is quite rare. Several cases
      have been reported in the literature, but no successful treatments for such
      metastases have ever been described. We herein report a case of esophageal cancer
      in which the ocular metastasis was controlled by systemic chemotherapy.

PMID- 15854986
TI  - Three-dimensional demonstration of the artery of Adamkiewicz with contrast
      enhanced magnetic resonance angiography.

PMID- 15854987
TI  - Cardiac fibroma.

PMID- 15854988
TI  - Repair of aortic leaflet prolapse: the "sliding leaflet technique".
AB  - Valve-preserving aortic replacement has become an accepted therapeutic option for
      aortic dilatation with normal valve leaflets. The presence of a leaflet prolapse
      often induces the choice of a composite graft repair. In these cases, however,
      the repair of a leaflet prolapse is possible and represents a valuable
      alternative to a prosthetic valve. The conventional techniques of repair of a
      cusp prolapse are designed to restore coaptation through a reduction of free
      margin length. The sliding leaflet technique is an alternative procedure
      conceived to repair the prolapsed valve cusp by remodeling both the free margin
      and the annular insertion.

PMID- 15854989
TI  - Assembly and deployment of a branched arch stent graft using the transaortic
      approach.
AB  - Transaortic stent grafting is an alternative method for treating distal arch
      aneurysms. Total arch grafts are too bulky to be inserted into a sheath catheter
      during usual stent grafting methods. An assembling method that uses a chain
      stitch enables the deployment of any type of stent graft into the distal aorta
      without the need for a sheath catheter. We describe how to safely assemble and
      use a branched arch stent graft. We consider this method to be beneficial in
      selected cases involving extensive distal arch aneurysms or in patients with
      highly calcified aortas.

PMID- 15854990
TI  - Effective use of fibrin glue for acute aortic dissection.
AB  - The use of gelatin-resorcine-formalin (GRF) glue for reconstruction of the
      vascular wall in the context of acute aortic dissection has become more common.
      However, anecdotal evidence suggests that use of the GRF glue results in higher
      rates of postoperative redissection. We describe an alternative method of
      reinforcing the dissected aorta with fibrin glue that may avoid this
      complication. A fabric sheet is presoaked in fibrinogen solution and then placed
      within the false lumen. Thrombin solution is then applied to the fabric sheet.
      That results in obliteration of the false lumen and effective reinforcement of
      the dissected wall.

PMID- 15854991
TI  - Left pulmonary arterioplasty--extended end-to-end anastomosis.
AB  - Surgical arterioplasty for left pulmonary branch stenosis often produces
      unsatisfactory results. We report a new operative approach involving a
      modification of end-to end anastomosis, providing a widely patent and
      nonredundant anastomosis.

PMID- 15854992
TI  - Development of the atrioventricular valves: clinicomorphological correlations.
AB  - The atrioventricular valves are formed from a complex arrangement of an annulus
      and leaflets, supported by a subvalvar apparatus that is composed of tendinous
      cords and papillary muscles. Although much has been said and written about their
      development, the exact nature of the process has yet to be fully elucidated. We
      believe that this is vital, since unraveling this complex process holds the key
      to the understanding of many of the congenital malformations that may afflict the
      valves.

PMID- 15854993
TI  - Internal thoracic artery: to skeletonize or not to skeletonize?
AB  - The internal thoracic artery has been the most reliable graft material used in
      coronary artery bypass grafting with an excellent long-term patency rate.
      Complete myocardial revascularization with internal thoracic arteries improves
      long-term survival and decreases the rate of repeat operations compared with vein
      grafts. Adequate length of the graft in coronary artery bypass graft surgery is
      essential for providing complete arterial revascularization. In the last decade
      or so, technique of skeletonization of internal thoracic artery has been proposed
      to achieve extra length. Skeletonization of the internal thoracic artery allows
      the preparation of longer conduits with a superior free flow and can reduce the
      incidence of postoperative pulmonary and sternal complications. However, concerns
      about vasoreactivity of skeletonized internal thoracic artery grafts, the
      functional consequences of surgical trauma, the possible loss of innervation, and
      vasa vasorum perfusion in the skeletonized conduits have prevented this technique
      from being universally accepted. Presently available evidence from retrospective
      studies (level 3 evidence) suggests that skeletonization is a safe and effective
      technique for myocardial revascularization. However, there is a need for
      conducting multicenter, randomized controlled trials comparing the skeletonized
      and pedicled internal thoracic arteries with special emphasis on long-term
      patency to conclusively validate the safety and efficacy of skeletonization
      technique.

PMID- 15854994
TI  - The clinical development of percutaneous heart valve technology: a position
      statement of the Society of Thoracic Surgeons (STS), the American Association for
      Thoracic Surgery (AATS), and the Society for Cardiovascular Angiography and
      Interventions (SCAI).

PMID- 15854995
TI  - A tribute to Giancarlo Rastelli.
AB  - Giancarlo Rastelli (1933-1970) was a pioneer cardiac surgeon who developed a
      classification of atrioventricular canal and a novel surgical procedure that
      revolutionized the management of children with congenital heart disease. Rastelli
      lived a short, yet fascinating life. His work was ahead of its time and laid the
      foundation for the treatment of complex congenital cardiac anomalies.

PMID- 15854997
TI  - Optimal surgical repair for double outlet right ventricle and intact ventricular
      septum.

PMID- 15854999
TI  - Left heart bypass during descending thoracic aneurysm repair.

PMID- 15855000
TI  - Repair of Ebstein's anomaly.

PMID- 15855001
TI  - Mitral valve repair.

PMID- 15855002
TI  - On decreasing distal endothelial damage after intracoronary shunt insertion.

PMID- 15855003
TI  - Patent ductus arteriosus in neonates and new approaches.

PMID- 15855005
TI  - Intrapleural bupivacine for postthoracotomy analgesia.

PMID- 15855007
TI  - Enhancement of CD4 and CD8 immunity by anti-CD137 (4-1BB) monoclonal antibodies
      during hepatitis C vaccination with recombinant adenovirus.
AB  - The induction of protective or therapeutic cellular immunity against hepatitis C
      virus (HCV) is a difficult goal. In a previous work we showed that immunization
      with a recombinant adenovirus encoding HCV-NS3 (RAdNS3) could partially protect
      mice from challenge with a vaccinia virus encoding HCV antigens. We sought to
      investigate whether systemic administration of an immunostimulatory monoclonal
      antibody directed against the lymphocyte surface molecule CD137 could enhance the
      immunity elicited by RAdNS3. It was found that treatment with anti-CD137 mAb
      after the administration of a suboptimal dose of RAdNS3 enhanced cytotoxic and T
      helper cell responses against HCV NS3. Importantly, the ability of RAdNS3 to
      induce protective immunity against challenge with a recombinant vaccinia virus
      expressing HCV proteins was markedly augmented. Thus, combination of
      immunostimulatory anti-CD137 mAb with recombinant adenoviruses expressing HCV
      proteins might be useful in strategies of immunization against HCV.

PMID- 15855008
TI  - Comparative efficacy of replicating smallpox vaccine strains in a murine
      challenge model.
AB  - There is currently considerable concern about the vulnerability of human
      populations to biowarfare or bioterrorist attacks with variola virus (VARV).
      Traditional smallpox vaccines were manufactured using the lymph of ruminants
      infected with the vaccinia virus (VACV). However, these production methods do not
      meet current standards for vaccines, especially since the emergence of
      transmissable spongiform encephalopathies in domesticated ruminants. This study
      has examined the protective efficacy of the Lister (Elstree) vaccine strain from
      various sources in a murine lethal challenge model. Considerable variation in
      efficacy is observed between the Lister material obtained from the American Type
      Culture Collection (ATCC) and the same strain obtained from vaccine stockpiles. A
      new, tissue-culture derived Lister vaccine is assessed against a bench-mark of
      multiple lots from a historical stockpile of the traditional vaccine. Apparent
      qualitative differences are observed between historical and new vaccines.
      Statistically significant differences are observed between different batches of
      the traditional vaccine, and the efficacy of the tissue-culture produced vaccine
      falls within this range.

PMID- 15855009
TI  - Self HSP60 peptide serves as an immunogenic carrier for a CTL epitope against
      persistence of murine cytomegalovirus in the salivary gland.
AB  - Murine cytomegalovirus (MCMV) infection is associated with persistence of virus
      in the salivary glands, despite relatively rapid clearance of virus from the
      spleen. An effective immunization against MCMV should prevent such viral
      persistence. We previously reported that a peptide (p458) from the sequence of
      the 60 kDa heat shock protein (HSP60) molecule in a conjugate vaccine can provide
      T cell help for the induction of protecting antibody against bacterial capsular
      polysaccharides. We now report that the p458 peptide as a carrier peptide can
      also enhance the immunogenicity of a dominant CTL epitope of the MCMV pp89
      antigen-89pep. We synthesized a linear combined peptide: chimeric p458-89pep. We
      immunized young BALB/c mice and challenged them with MCMV. We found that the p458
      89pep chimeric peptide was more effective than the 89pep in inducing 89pep
      specific IFN(gamma) secretion and specific CTL activity. Moreover, the p458-89pep
      chimeric peptide induced sustained IFN(gamma) secretion in the salivary gland
      specific to 89pep and only this immunization was associated with clearance of
      virus from the salivary gland. These results suggest that a peptide epitope of
      HSP60 may be advantageous as a T cell carrier peptide in the induction of
      specific T cell immunity against infectious agents.

PMID- 15855010
TI  - Disparities in varicella vaccine coverage in the absence of public funding.
AB  - Varicella vaccine has been licensed in Canada since December 1998 but not
      provided free in all provinces. Through a cross-sectional telephone survey to a
      random sample of parents, we assessed factors associated with varicella vaccine
      uptake in the absence of public funding. Parents of children aged 2-3 years
      (Group I) and 6-7 years (Group II) were contacted between March and May 2003 in
      British Columbia, Canada. Response rate was 82% (Group I=571; Group II=704).
      Among susceptible children, varicella vaccine coverage was 21% (95% CI 18-25%)
      and 28% (95% CI 22-33%), respectively. There were significant disparities in
      vaccine coverage based on income and residence. Physician or nurse recommendation
      was a strong determinant of vaccine uptake as were belief in the safety and
      efficacy of vaccine. Among parents of susceptible children, 59% (343/582) would
      vaccinate their child if it were provided free; 25% (148/582) were undecided.

PMID- 15855011
TI  - Heat-shock protein 70 acts as an effective adjuvant in neonatal mice and confers
      protection against challenge with herpes simplex virus.
AB  - Immunization of the neonate is a highly desirable goal for vaccine developers,
      since the neonate is profoundly susceptible to a number of viral and bacterial
      pathogens. The neonatal immune system tends to generate Th2 recall responses,
      known as neonatal tolerance, which may not protect against viral challenge later
      in life. In this study we demonstrate that a potent immune proinflammatory
      stimulator, heat-shock protein 70 (hsp70), can act as an effective and safe
      adjuvant in neonates. Priming of neonates with hsp70 coupled to a viral MHC Class
      I-restricted epitope (gB498-505) and injection with recombinant gB generated
      strong cytotoxic T lymphocyte (CTL) responses and a Th1 primary T helper cell
      response during the neonatal period. In addition, enhanced CTL and predominant
      Th1 recall responses to viral antigens were observed following secondary
      challenge as adults. These responses were sufficient to allow protection against
      a lethal challenge with Herpes Simplex Virus Type-1 (HSV-1). Therefore, hsp70 in
      conjunction with viral epitopes and recombinant viral protein can perhaps prime
      protective immune responses to herpes viruses early in life when infection, which
      can be life-threatening, and the establishment of latency frequently occur.

PMID- 15855012
TI  - Immune response of vaccinated and non-vaccinated mice to Coccidioides posadasii
      infection.
AB  - An immunogenic, recombinant protein of the fungal respiratory pathogen,
      Coccidioides posadasii, was previously identified as a beta-1,3
      glucanosyltransferase homolog (Gel1) and shown to confer protection to C57BL/6
      mice against coccidioidomycosis. However, little is known about the nature of the
      humoral and cellular immune responses of these vaccinated mice to intranasal
      infection with a lethal inoculum of C. posadasii spores compared to non-immune
      control animals. Our studies showed that protective immunity in mice vaccinated
      with two 1 microg doses of the recombinant Gel1 (rGel1) plus adjuvant was
      characterized by high titers of antigen-specific IgG2c and elevated levels of
      interleukin (IL)-12 and interferon-gamma (IFN-gamma) production at 7-14 days post
      challenge compared to significantly lower levels of the respective antibody and
      cytokines in non-immune, infected mice. Mice immunized with either 0.2 or 5
      microg doses of rGel1 plus adjuvant were less well protected and showed evidence
      of a marked decrease in the level of T helper-type 1 (T(H)1) immune response.
      Early T(H)1 immune regulation is essential for protection against pulmonary
      infection with Coccidioides, and the dose of the rGel1 vaccine narrowly defines
      the nature of immune response in the lungs of infected mice.

PMID- 15855013
TI  - Development of a CTL vaccine for Her-2/neu using peptide-microspheres and
      adjuvants.
AB  - With the ultimate goal of developing a therapeutic cancer vaccine, we
      encapsulated the Her-2/neu peptide p369-377 in poly(lactide-co-glycolide)
      microspheres. This formulation was found to effectively elicit CD8+ cytotoxic T
      cell (CTL) responses in an HLA-A*0201 transgenic mouse model. In contrast,
      immunization with either peptide alone or peptide formulated in incomplete
      Freund's adjuvant (IFA) failed to elicit such CTL responses. Responses induced by
      the peptide-microsphere formulation were found to peak at approximately 6 weeks
      post-immunization, and were enhanced by delivering increased doses of peptide and
      with repeated administrations over time. Co-administration of the peptide
      microspheres with adjuvants, including granulocyte-macrophage colony stimulating
      factor, MPL adjuvant and select synthetic Toll-Like Receptor 4 ligands, the
      aminoalkyl glucosaminide-4 phosphates, significantly augmented CTL responses.
      These studies provide important guidance for the design of human clinical trials
      of microsphere vaccines in terms of optimal peptide-microsphere formulation,
      vaccination regimen, vaccine dose, and adjuvant selection.

PMID- 15855014
TI  - HPV-16 L1 VLP vaccine elicits a broad-spectrum of cytokine responses in whole
      blood.
AB  - Here, we evaluated innate and adaptive immune system cytokine responses induced
      by HPV-16 L1 VLP in whole blood (WB) cultures from individuals receiving the
      vaccine (n=20) or placebo (n=4) before and after vaccination. 11 cytokines were
      measured: IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-gamma, TNF
      alpha, and GM-CSF using multiplex bead arrays. Cytokine profiles from WB samples
      clearly discriminated between vaccine and placebo recipients and between pre and
      post-vaccination responses. Significant increases in Th1, Th2 and inflammatory
      cytokines were observed in WB assays following vaccination. Results from WB
      assays were compared against parallel PBMC-based assays in a subset of patients.
      Differences between whole blood assay and PBMC were observed, with the highest
      levels of induction found for WB for several cytokines. Our results indicate that
      multiplex assays for cytokine profiling in WB are an efficient tool for assessing
      broad spectrum, innate and adaptive immune responses to vaccines and identifying
      immunologic correlates of protection in efficacy studies.

PMID- 15855015
TI  - Tumor immunity and prolonged survival following combined adenovirus-HSP72 and CEA
      plasmid vaccination.
AB  - We have studied the effects of recombinant adenoviruses as immune adjuvants for
      DNA vaccination. In a mouse model, using the weak immunogen carcinoembryonic
      antigen (CEA), anti-CEA IgG production was significantly higher and occurred
      earlier when immunization included a recombinant adenovirus together with CEA
      plasmid DNA. Combined immunization with a recombinant adenovirus expressing the
      immunomodulatory molecule heat shock protein 72 (ADHSP72) and CEA-plasmid DNA
      resulted in CEA-specific T-cell activation capable of protecting mice from tumor
      formation with CEA expressing cells. Additionally, animals with CEA expressing
      tumors showed diminished tumor growth and prolonged survival when immunized with
      ADHSP72 and CEA-plasmid DNA compared to controls. Recombinant adenoviruses
      expressing immunomodulatory molecules such as HSP72 may be useful adjuvants for
      DNA vaccination.

PMID- 15855016
TI  - Interactions between helper T-cell epitopes of hepatitis C virus.
AB  - The premise of this work is that within a given hepatitis C virus (HCV) protein
      there exists an array of Th1 and Th2 epitopes, each of which can provide
      synergistic (positive or negative) effects upon other epitopes by intramolecular,
      cytokine-mediated immunoregulation of helper T-cell responses. To address this
      question, we constructed minigene plasmids pHCVTh1, pHCVTh1X3 and pHCVThR, and
      HCV NS3 full-length plasmid pHCVNS3. 293T cells were transfected with these
      plasmids and cell lysates from the transfected cells were used to stimulate PBMC
      from a patient with chronic HCV infection. IL-2 and IFN-gamma in the supernatant
      of the cultured PBMC were tested and proliferation of the PBMC was measured. The
      results demonstrate that interactions exist among helper T-cell epitopes; the
      synergistic effects of suppressive Th2 epitopes upon Th1 epitopes will inhibit
      the responses induced by Th1 epitopes, which may contribute to chronic infection
      by HCV; synergistic effects among Th1 epitopes induce higher levels of IFN-gamma,
      which may suggest a new strategy for HCV vaccine development. Further,
      stimulation of an HCV NS3 specific clone with cell lysates from 293T cells
      transfected with different constructs shows that the HCV NS3 clone could respond
      to all suggesting that the epitope-specific suppression may be due to an
      imbalance of Type 1 and Type 2 cytokines or regulatory T-cells.

PMID- 15855017
TI  - Effect of oral vaccination of cattle with lipid-formulated BCG on immune
      responses and protection against bovine tuberculosis.
AB  - Cattle were given Mycobacterium bovis bacillus Calmette-Guerin (BCG) in a lipid
      based formulation via the oral route and tested for immune responses and
      protection against a challenge with virulent M. bovis. Calves were vaccinated by
      orally administering a pellet containing 10(8) colony forming units (CFU) of BCG,
      or 10 pellets containing a total of 10(9) CFU of BCG, whereas positive controls
      were injected subcutaneously with 10(6) CFU of BCG. All of the subcutaneously
      vaccinated calves produced positive responses in the caudal fold tuberculin skin
      test at 8 weeks after vaccination, whereas only 3/9 of the low dose and 6/10 of
      the high dose orally-vaccinated animals produced positive reactions. None of the
      animals produced positive reactions to the mycobacterial antigens, ESAT-6 and
      CFP10 in the interferon-gamma (IFN-gamma) test and only a total of four of the
      BCG-vaccinated animals produced positive responses in either the standard IFN
      gamma or comparative cervical skin test. Oral administration of 10 pellets of
      lipid-formulated BCG to cattle induced a significant level of protection against
      bovine tuberculosis compared to that observed in non-vaccinated animals and this
      level was similar to that seen in the BCG subcutaneously vaccinated animals. Oral
      vaccination of BCG in a lipid-formulation to calves was shown to induce some
      positive tuberculin skin test reactions, but could also induce protection against
      bovine tuberculosis.

PMID- 15855018
TI  - Role of an immunodominant T cell epitope of the P6 protein of nontypeable
      Haemophilus influenzae in murine protective immunity.
AB  - Nontypeable Haemophilus influenzae (NTHI) is a common cause of otitis media in
      children and lower respiratory tract infection in adults with chronic lung
      disease. The highly conserved P6 protein of NTHI infection is under evaluation as
      a vaccine antigen in several animal models. To elucidate the role of cellular
      immune response to P6 in protective immunity, the goal of this study was to
      identify and characterize T cell epitope(s) on P6 and to investigate the role of
      these epitope(s) in eliciting antigen specific antibody responses and in
      mediating pulmonary clearance of NTHI. We report that T cells from BALB/c
      immunized with P6 recognize a single, immunodominant region, represented by 15
      amino acids (residues 41-55) of the P6 protein. To verify the ability of this
      epitope to elicit T cell responses to the P6 protein, mice were immunized with a
      synthetic peptide corresponding to the sequence of dominant peptide. T cells
      isolated from mice primed in vivo with the peptide responded following in vitro
      stimulation with either the peptide or with the whole P6 molecule. Substitution
      of single amino acids and N or C terminal truncations of the dominant peptide
      resulted in complete abrogation of the response, implicating their importance to
      the T cell response. Furthermore, mucosal immunization of mice with a chimeric
      peptide that encompassed the dominant T cell epitope and a putative B cell
      epitope resulted in enhanced bacterial clearance following pulmonary challenge
      with NTHI. Collectively, these results establish that, in a mouse model, P6
      contains a single immunodominant T cell epitope and this epitope plays an
      important role in protective immune responses induced by immunization with P6.

PMID- 15855019
TI  - PyNTTTTGT prototype oligonucleotide IMT504 is a potent adjuvant for the
      recombinant hepatitis B vaccine that enhances the Th1 response.
AB  - PyNTTTTGT oligodeoxinucleotides (ODNs) cause activation, proliferation and
      immunoglobulin secretion on B cells, and the expression of co-stimulatory
      molecules on plasmacytoid dendritic cells of primates. It has now been discovered
      that these ODNs are also active on rat cells. This fact allowed us to investigate
      the adjuvant properties of PyNTTTTGT ODNs in a human Hepatitis B vaccine using
      this animal model. A very significant increment, as compared with the antigen
      alone, was observed in the antibody production induced by vaccination with the
      recombinant Hepatitis B surface antigen adjuvated with the PyNTTTTGT prototype
      IMT504 ODN. Analysis of the IgG subclass distribution in the sera of vaccinated
      animals indicated that, although an increase was observed in the titer of all the
      IgG subclasses, the increase on the Th1-associated IgG2b subclass was clearly
      more pronounced. Remarkably, this effect on the IgG2b titer was observed even if
      alum, a Th2 promoting adjuvant, was present together with IMT504 in the vaccine
      formulation. The increase in the Th1 response induced by IMT504 was also
      suggested by in vitro gamma interferon secretion assays. Monkeys of the species
      Cebus apella immunized with the recombinant Hepatitis B surface antigen plus alum
      and IMT504 also showed titers of antibodies against the antigen several times
      superior to the titers observed in control animals immunized with the antigen
      plus alum without ODN. Since rat and monkey cells are significantly less
      immunostimulated "in vitro" by PyNTTTTGT ODNs than human cells, the present
      results reasonably predict a very good performance of these ODNs as adjuvants in
      human vaccination.

PMID- 15855020
TI  - Factors influencing influenza vaccination uptake in an elderly, community-based
      sample.
AB  - This study investigated predictors of influenza vaccination uptake since the
      introduction of the policy to target over 65s. Four hundred and forty-four
      participants completed a cross-sectional structured interview. The predictors of
      vaccination uptake were: having a doctor or nurse who explained why the
      vaccination is important and possible side effects; living with others; higher
      occupational status; and having a car or being able to walk to the GPs rather
      than reliant on others or public transport. Most participants who had received
      the vaccination reported having done so in response to reminders or advice from
      medical professionals. The most common explanations given by those who had chosen
      not to receive the vaccination were fear of side effects and concerns regarding
      vaccination efficacy. Current national campaigns and general practitioners'
      reminder programmes appear to have been successful in improving awareness;
      however, these results suggest that a more informational campaign, focused on the
      evidence that the vaccine is efficacious and that side effects are limited, may
      further improve uptake.

PMID- 15855021
TI  - Comparative immunogenicity of the hepatitis B virus core 149 antigen displayed on
      the inner and outer membrane of bacterial ghosts.
AB  - Two membrane compartments of Escherichia coli ghosts, representing empty
      bacterial cell envelopes, were investigated as carriers of foreign antigens. By
      subcutaneous immunisation of mice the immunogenicity of bacterial ghosts carrying
      the Hepatitis B virus core 149 protein (HBcAg-149) as model antigen anchored
      either in the inner or the outer membrane of E. coli was compared. Both systems
      induced significant immune responses against the foreign target antigen, the
      HBcAg-149, in mice. Results indicate that bacterial ghosts provide an excellent
      carrier system for antigen delivery.

PMID- 15855022
TI  - DNA vaccination for the priming of neutralizing antibodies against non
      immunogenic STa enterotoxin from enterotoxigenic Escherichia coli.
AB  - In order to test the use of DNA vaccination for its capacity to induce antibodies
      against the non-immunogenic heat-stable enterotoxin STa from Escherichia coli,
      BALB/c mice were immunized with plasmid DNA encoding hybrid proteins made by the
      insertion of wild type STa or insertion of the Cys6Ala, Cys17Ala and Cys6Ala
      Cys17Ala STa mutants at positions 195 or 216 of the TEM-1 beta-lactamase. No STa
      specific antibodies could be detected after three plasmid injections, but a
      subsequent boost with native STa peptide was capable of inducing low levels of
      neutralizing antibodies, as tested in the suckling mouse assay. Highest STa
      specific responses were found in mice primed with the double mutated STa inserted
      in position 195. This plasmid induced highest T-cell responses to the TEM-1
      protein, indicating that priming of helper T-cell responses to the carrier
      protein was essential. Mixed IgG1/IgG2a isotypes also reflected this T helper 1
      type priming. Moreover, insertion into loop A of the TEM-1 carrier may be more
      suitable than insertion into loop B, because of reduced competition between
      carrier and hapten B cell responses.

PMID- 15855024
TI  - Preoperative differences of cerebral metabolism relate to the outcome of cochlear
      implants in congenitally deaf children.
AB  - In congenitally deaf children, chronological age is generally accepted as a
      critical factor that affects successful rehabilitation following cochlear
      implantation (CI). However, a wide variance among patients is known to exist
      regardless of the age at CI [Sarant, J.Z., Blamey, P.J., Dowell, R.C., Clark,
      G.M., Gibson, W.P., 2001. Variation in speech perception scores among children
      with cochlear implants. Ear Hear. 22, 18-28]. In a previous study, we reported
      that prelingually deaf children in the age range 5-7 years at implantation showed
      greatest outcome variability [Oh S.H., Kim C.S., Kang E.J., Lee D.S., Lee H.J.,
      Chang S.O., Ahn S.H., Hwang C.H., Park H.J., Koo J.W., 2003. Speech perception
      after cochlear implantation over a 4-year time period. Acta Otolaryngol. 123, 148
      153]. Eleven children who underwent CI between the age of 5 and 7 1/2 years were
      subdivided into a good (above 65%: GOOD) and a poor (below 45%: POOR) group based
      on the performance in a speech perception test given 2 years after CI. The
      preoperative (18)F-FDG-PET (F-18 fluorodeoxyglucose positron emission tomography)
      images were compared between the two groups in order to examine if regional
      glucose metabolic difference preexisted before the CI surgery. In the GOOD group,
      metabolic activity was greater in diverse fronto-parietal regions compared to the
      POOR group. In the POOR group, the regions related to the ventral visual pathway
      showed greater metabolic activity relative to the GOOD group. These findings
      suggest that the deaf children who had developed greater executive and
      visuospatial functions subserved by the prefrontal and parietal cortices might be
      successful in auditory language learning after CI. On the contrary, greater
      dependency on the visual function subserved by the occipito-temporal region due
      to auditory deprivation may interfere with acquisition of auditory language after
      CI.

PMID- 15855025
TI  - Asynchronous inputs alter excitability, spike timing, and topography in primary
      auditory cortex.
AB  - Correlation-based synaptic plasticity provides a potential cellular mechanism for
      learning and memory. Studies in the visual and somatosensory systems have shown
      that behavioral and surgical manipulation of sensory inputs leads to changes in
      cortical organization that are consistent with the operation of these learning
      rules. In this study, we examine how the organization of primary auditory cortex
      (A1) is altered by tones designed to decrease the average input correlation
      across the frequency map. After one month of separately pairing nucleus basalis
      stimulation with 2 and 14 kHz tones, a greater proportion of A1 neurons responded
      to frequencies below 2 kHz and above 14 kHz. Despite the expanded representation
      of these tones, cortical excitability was specifically reduced in the high and
      low frequency regions of A1, as evidenced by increased neural thresholds and
      decreased response strength. In contrast, in the frequency region between the two
      paired tones, driven rates were unaffected and spontaneous firing rate was
      increased. Neural response latencies were increased across the frequency map when
      nucleus basalis stimulation was associated with asynchronous activation of the
      high and low frequency regions of A1. This set of changes did not occur when
      pulsed noise bursts were paired with nucleus basalis stimulation. These results
      are consistent with earlier observations that sensory input statistics can shape
      cortical map organization and spike timing.

PMID- 15855026
TI  - Erythropoietin and erythropoietin receptor expression in the guinea pig inner
      ear.
AB  - The erythropoietin receptor (EPOR) is expressed in the brain and erythropoietin
      (EPO) has been shown to have neurotrophic and neuroprotective functions in the
      central nervous system and in the retina. These findings may be applied to the
      inner ear, pending EPO receptor presence. Accordingly, this study determines
      expression of EPO and EPOR in the inner ear of the guinea pig. Normal guinea pig
      inner ears were processed for immunohistochemistry, using poly-clonal antibodies
      against EPO and the EPO receptor. EPO expression was exclusively found in most,
      but not all spiral ganglion neurons. Expression of the EPO receptor was found in
      the cytoplasm of the inner and outer phalangeal cells (Deiters' cells), as well
      as the inner sulcus cells and the supporting cells of the organ of Corti (Hensen,
      Claudius and some Boettcher cells). Some spiral ganglion neurons or glial cells
      expressed the receptor, as did spiral ligament fibrocytes, some intermediate
      cells of stria vascularis and the endothelial cells of some modiolar vessels. No
      parts of the vestibular system stained positive for either antibody. We conclude,
      that EPO is expressed by spiral ganglion neurons and that the EPO receptor is
      widely expressed by several cell types within the guinea pig cochlea. We
      hypothesize on the existence of a local paracrine system and that EPO treatment
      may be feasible following inner ear damage.

PMID- 15855027
TI  - Audio-vestibular disturbances in Behcet's patients: report of 62 cases.
AB  - This study was carried out to determine the characteristics and incidence of
      hearing loss and vestibular disturbance in Behcet's syndrome with a large number
      of patients. Sixty-two patients with Behcet's syndrome were included in this
      study, 34 men and 28 women whose mean age was 33.7 (15-60). Sixty-two healthy
      normal control subjects (38 male and 24 female) were included. Patient and
      control groups were questioned about any history of audio-vestibular disturbance
      and underwent physical and ENT examination and the following audiologic tests:
      pure tone audiometric test (0.25, 0.5, 1, 2, 4, and 6 kHz), tympanogram, speech
      discrimination, short increment sensitivity index, tone-decay test, auditory
      brainstem response. Vestibular system was evaluated by videonistagmogram and
      caloric test. Cranial and brainstem magnetic resonance imagine (MRI) of patients
      who have vestibular disturbances were practiced to examine the central nervous
      system. Both the patient and the control groups were tested with the HLA-B51
      antigen. Pure tone audiogram showed sensory-neural hearing loss (25 dB hearing
      level in at least two frequencies) in 20 of the 62 (32%) Behcet's patients while
      the control group were normal. There was a hearing loss involving high
      frequencies in the audiograms of Behcet's patients with hearing disturbances. The
      recruitment investigation tests and auditory brain stem response confirmed
      cochlear involvement in all 20 patients. Caloric stimulation tests revealed a
      normal vestibular function in all patient and control group. In
      electronystagmography, 21 (34%) patients had hypometric or hypermetric saccades
      and smooth pursuit tests showing that 4 (6%) patients had pathological changes
      while the control group was normal. HLA-B51 antigen was found positive in 15 of
      20 Behcet's patient with hearing loss. CONCLUSION: (1) The hearing and vestibular
      disturbances in Behcet's syndrome is more prevalent than previously recognized;
      (2) Hearing loss in high frequencies in Behcet's patients is an indicator of
      cochlear involvement in this disease; (3) There is a higher prevalence of central
      vestibular syndrome in Behcet's patients than it was thought before; (4) HLA-B51
      antigen may be able to be a prognostic factor for sensorineural hearing loss in
      Behcet's patients.

PMID- 15855028
TI  - The effects of nembutal anesthesia on the auditory steady-state response (ASSR)
      from the inferior colliculus and auditory cortex of the chinchilla.
AB  - We examined the effects of nembutal anesthesia on the amplitude of the auditory
      steady-state response (ASSR) in the inferior colliculus (IC) and auditory cortex
      (AC) of the chinchilla. Tungsten electrodes were chronically implanted following
      anesthesia with ketamine/acepromazine. After a recovery period, the chinchillas
      were placed in a passive restraining device and put in a sound-attenuating booth.
      Recordings were made from the right IC and AC simultaneously, while a two-tone
      stimulus was presented to the left ear. The stimuli consisted of two equal-level
      tones (F1 and F2) that were mixed acoustically; F1 remained constant at 2000 Hz,
      while F2 varied between 2029 and 2249 Hz, in steps of approximately 20 Hz. The
      stimuli decreased in 10 dB steps from 80 to 30 dB pSPL. Animals were evaluated
      when unanesthetized, as well as when anesthetized with nembutal (on separate
      days). In the IC, the administration of nembutal resulted in either no change in
      ASSR amplitude or an amplitude increase for difference tone (DT) frequencies
      below 90 Hz, while an amplitude decrease was typically seen for DT frequencies at
      or above 90 Hz. In the AC, a decrease in amplitude was seen across DT frequencies
      and stimulus levels after the administration of nembutal anesthesia. Our results
      suggest that both the AC and IC may contribute to the scalp-recorded ASSR in the
      awake state. However, in the nembutal-anesthetized state, it seems unlikely that
      the AC contributes substantially to the surface-recorded ASSR, as the AC response
      was greatly attenuated under nembutal anesthesia. In contrast, the IC ASSR
      responses remained robust, which makes it a likely contributor to the surface
      recorded responses under nembutal anesthesia.

PMID- 15855029
TI  - Dependence of the DPOAE amplitude pattern on acoustical biasing of the cochlear
      partition.
AB  - Distortion product otoacoustic emissions (DPOAEs) were recorded from guinea pigs
      in response to simultaneous increases in the levels of high frequency primary
      tones in the presence of a low frequency biasing tone of 30 Hz at 120 dB SPL. The
      DPOAE amplitudes plotted as functions of the biasing tone phase angle show
      distinctive repeatable minima, which are identical to the amplitude notches
      observed for the distortion products at the output of a single saturating non
      linearity. The number of the amplitude minima grows with increasing order of the
      DPOAE, a feature that is also reproduced by the model. The model of DPOAE
      generation due to a single saturating non-linearity does not explain the
      experimentally observed asymmetry of the response of the DPOAEs to rising and
      falling half cycles of the biasing tone. This asymmetry is attributed to a
      hypothetical mechanism, which adjusts the operating point of the outer hair
      cell's mechanoelectrical transducer. Experimental data were consistent with a
      hypothesis that, for the parameters of stimulation used in this study, both lower
      and upper sideband DPOAEs are dominated by emission generated from a single and
      spatially localized place in the cochlea.

PMID- 15855030
TI  - A temporal bone study of insertion trauma and intracochlear position of cochlear
      implant electrodes. I: Comparison of Nucleus banded and Nucleus Contour
      electrodes.
AB  - In recent years, new designs of cochlear implant electrodes have been introduced
      in an attempt to improve efficiency and performance by locating stimulation sites
      closer to spiral ganglion neurons and deeper into the scala tympani. The goal of
      this study was to document insertion depth, intracochlear position and insertion
      trauma with the Nucleus Contour electrode and to compare results to those
      observed with the earlier generation Nucleus banded electrode. For this
      comparison eight Nuclears banded electrodes and 18 Contour electrodes were
      implanted in cadaver temporal bones using a realistic surgical exposure. Two
      experienced cochlear implant surgeons and two otology fellows with specialized
      training in cochlear implant surgery were selected for the study to represent a
      range of surgical experience similar to that of surgeons currently performing the
      procedure throughout the world. Following insertion of the electrodes, specimens
      were imaged using plain film X-ray, embedded in acrylic resin, cut in radial
      sections with the electrodes in place, and each cut surface was polished.
      Insertion depth was measured in digitized X-ray images, and trauma was assessed
      in each cross-section. The Contour electrode inserted more deeply (mean
      depth=17.9 mm or 417 degrees ) than the banded electrode (mean depth=15.3 mm or
      285 degrees ). The incidence and severity of trauma varied substantially among
      the temporal bones studied. However, the nature and frequency of injuries
      observed with the two devices were very similar. The Contour electrode was
      clearly positioned closer to the modiolus than the banded model, and also
      appeared easier to use. Based on this difference in position and data from
      previous studies we conclude that the Contour electrode may provide lower
      thresholds and improved channel selectivity, but the incidence of trauma remains
      a problem with the newer design. The relative influences of electrode positioning
      and neural degeneration that may result from trauma are as yet unclear.

PMID- 15855031
TI  - A temporal bone study of insertion trauma and intracochlear position of cochlear
      implant electrodes. II: Comparison of Spiral Clarion and HiFocus II electrodes.
AB  - In recent years, several new designs of cochlear implant electrodes have been
      introduced clinically with the goal of optimizing perimodiolar placement of
      stimulation sites. Previous studies suggest that perimodiolar electrodes may
      increase both the efficiency and performance of a cochlear implant. This is the
      second of two studies designed to examine the positioning of electrodes and the
      occurrence of insertion-related injury with these newer designs and to directly
      compare two perimodiolar electrodes to their predecessors. In our previous report
      we compared the Nucleus banded electrode with the Nucleus Contour perimodiolar
      electrode. In the present study, using the same protocol, we examine the Spiral
      Clarion electrode and its successor, the HiFocus II electrode with attached
      positioner. Eight Spiral Clarion arrays and 20 HiFocus II electrodes with
      positioners were inserted into human cadaver temporal bones. Following insertion,
      the specimens were embedded in acrylic resin, cut in quarters with a diamond saw
      and polished. Insertion depth, proximity to the modiolus and trauma were
      evaluated in X-ray images and light microscopy. The newer electrode was
      consistently positioned closer to the modiolus than the previous device whereas
      the angular depth of insertion measured for the two electrodes was similar. The
      incidence of trauma was minimal when either electrode was inserted to a depth of
      less than 400 degrees . However, severe trauma was observed in every case in
      which the HiFocus II with positioner was inserted beyond 400 degrees and in some
      cases in which the Spiral Clarion was inserted beyond 400 degrees . To evaluate
      the possible role of electrode size in the trauma observed we modeled both
      devices relative to the dimensions of the scala tympani. We found that the fully
      inserted HiFocus II electrode with positioner was larger than the scala tympani
      in approximately 70% of temporal bones measured. The results suggest that both
      the Clarion spiral and HiFocus II with positioner can be inserted with minimal
      trauma, but in many cases not to the maximum depth allowed by the design.

PMID- 15855032
TI  - Acceleration of cisplatin ototoxicity by perilymphatic application of 4
      methylthiobenzoic acid.
AB  - The antitumor agent cisplatin has dose-limiting side effects such as ototoxicity.
      Systemical co-treatment with anti-oxidants like 4-methylthiobenzoic acid (MTBA)
      and sodium thiosulfate (STS) provides protection against cisplatin ototoxicity.
      However, systemically administered protective agents may reduce the
      chemotherapeutic effect of cisplatin. Local application of the protective agents
      could avoid this undesirable effect. In the present study, we aimed at
      suppressing cisplatin-induced ototoxicity in guinea pigs by administering MTBA or
      STS perilymphatically through cochlear perfusion. Guinea pig cochleas were
      perfused for 10 min with artificial perilymph (ArtP) containing cisplatin at 0.3
      mg/ml, either alone, or in combination with MTBA (0.1 or 1.0 mg/ml) or STS (0.75
      or 3.0 mg/ml). The compound action potential (CAP) and the summating potential
      (SP), evoked by 8 kHz tone bursts, and the endocochlear potential (EP; MTBA only)
      were measured just before and 1, 2, 3 and 4 h after perfusion. Cisplatin
      gradually reduced the CAP amplitude in time. Adding MTBA only accelerated this
      ototoxic effect. After cisplatin treatment a decline was found in the EP,
      irrespective of co-treatment, i.e., addition of MTBA did not accelerate the EP
      decrease. In contrast to MTBA, STS ameliorated the ototoxic effect of cisplatin.
      In conclusion, local application of anti-oxidants can ameliorate cisplatin
      ototoxicity but this is not a feature of all anti-oxidants.

PMID- 15855033
TI  - GJB2 mutations in Turkish patients with ARNSHL: prevalence and two novel
      mutations.
AB  - Mutations in the connexin 26 gene (GJB2) cause a significant proportion of
      prelingual non-syndromic autosomal recessive deafness in all populations studied
      so far. To determine the percentage of hearing loss attributed to GJB2 in
      northeast Turkey, 93 unrelated patients with autosomal recessive non-syndromic
      hearing loss (ARNSHL) were screened. Seven different mutations were found in 29
      of the patients with severe to profound hearing loss. The 35delG mutation was the
      most common mutation, accounting for 76% of all mutant GJB2 alleles. Four already
      described mutations, W24X, 310del14, delE120 and R184P and two novel mutations,
      Q80K and P173S, were identified. The allelic Delta(GJB6-D13S1830), which can
      cause hearing loss in combination with GJB2 mutations, was not present in our
      patients. Our results are comparable to those reported in other regions in Turkey
      and indicate that GJB2 mutations account for about 30% of Turkish patients with
      ARNSHL. Besides 35delG, W24X and delE120 occur more than once in the Turkish
      ARNSHL population with a frequency of about 5%.

PMID- 15855034
TI  - Involvement of nitric oxide generation in noise-induced temporary threshold shift
      in guinea pigs.
AB  - The present study explored the role of endogenous nitric oxide (NO) in the
      temporary threshold shift caused by acoustic trauma. Guinea pigs were exposed to
      broadband white noise at a level of 105+/-2dB sound pressure level (SPL) for
      10min, causing a temporary threshold shift (TTS). The guinea pigs were divided
      into six groups (N-1 to N-6) according to survival days after noise exposure (0,
      1, 2, 3, 7, 28days). Auditory brainstem responses (ABR) were recorded before
      noise exposure, immediately after noise exposure and before sacrifice.
      Immediately after animals were sacrificed, the stria vascularis and the spiral
      ligament of the lateral wall of each individual cochlea were harvest as a unit
      and prepared for assay of NO. There was a significant correlation (P<0.001)
      between the NO concentration and final ABR threshold in the noise exposure
      groups. But the return of ABR threshold to pre-noise-exposed level is early than
      that of NO concentration. An average 16.2dB threshold shift was found immediately
      after noise exposure. The threshold returned to the pre-noise-exposed level on
      the second post-exposure day. Comparing to unexposed control animals, the NO
      concentration increased nearly threefold immediately following noise exposure and
      decreased to twofold when the hearing threshold had returned to the pre-noise
      exposed level. On the seventh post-exposure day the NO concentration was not
      different from that in unexposed control animals. Those findings indicate that
      endogenous NO is generated in the noise-induced temporal threshold shift and its
      concentration is correlated with the hearing loss.

PMID- 15855035
TI  - Breed-dependent susceptibility to acute sound exposure in young chickens.
AB  - Commercially available chickens fall into two categories: egg layers and
      broilers. Durham et al. (Hear. Res. 166 (2002) 82-95) showed that despite similar
      noisy living environments, cochleae of most adult broilers show extensive damage,
      while cochleae of adult egg layers are largely normal. This finding suggests that
      egg layers and broilers differ in their susceptibility to noise damage. Here, we
      evaluate breed differences in susceptibility to acoustic trauma. Young egg layers
      and broilers (10-17 weeks) were exposed to a 1500Hz pure tone (120dB SPL; 24h)
      and killed 24 or 72h later. Cochleae were prepared for scanning electron
      microscopy and photomicrographs of the cochlear surface were used to determine
      location and severity of damage. Cochleae were grouped based upon damage severity
      (moderate or severe). While location and area of damage were similar between both
      breeds at each recovery time, cochlear damage at 72h was more extensive than at
      24h. We found no quantitative breed differences within either damage category or
      recovery time. However, more egg layers (25/27) than broilers (16/32) displayed
      severely damaged cochleae. Our findings conflict with those reported by Durham et
      al. (2002). Our results identify a breed-dependent difference in susceptibility
      to acute sound exposure, with young egg layers displaying increased sensitivity.

PMID- 15855036
TI  - Immunohistochemical detection of platinated DNA in the cochlea of cisplatin
      treated guinea pigs.
AB  - Cisplatin-induced ototoxicity is correlated with functional and morphological
      changes in the organ of Corti, the stria vascularis and the spiral ganglion.
      However, the cochlear sites of cisplatin uptake and accumulation have not been
      properly identified. Therefore, we have developed an immunohistochemical method
      to, indirectly, detect cisplatin in semithin cryosections of the guinea pig
      cochlea (basal turn) using an antiserum containing antibodies against cisplatin
      DNA adducts. Platinated DNA was present in the nuclei of most cells in the organ
      of Corti and the lateral wall after cisplatin administration. Nuclear
      immunostaining was most pronounced in the outer hair cells, the marginal cells
      and the spiral ligament fibrocytes. This study is the first to demonstrate the
      presence of cisplatin in histological sections of the cochlea.

PMID- 15855037
TI  - Transient evoked otoacoustic emissions recorded using maximum length sequences
      from patients with sensorineural hearing loss.
AB  - Much research has shown that transient evoked otoacoustic emissions (TEOAEs) can
      successfully separate normally hearing and hearing impaired populations. However,
      this finding comes from TEOAEs recorded using conventional averaging at low
      stimulation rates. Presenting clicks according to maximum length sequences (MLSs)
      enables TEOAEs to be recorded at very high stimulation rates. This study compares
      conventional and MLS TEOAEs in normally hearing and hearing impaired adults.
      Stimulus presentation rates of 40 clicks/s (conventional) and 5000 clicks/s (MLS)
      were used. The 'linear' TEOAEs (i.e., the directly recorded waveforms), the
      'level nonlinear' (LNL) TEOAEs (i.e., those derived from two linear waveforms
      separated by a known difference in stimulus level) and the 'rate nonlinear' (RNL)
      TEOAEs (i.e., obtained by subtracting the emission recorded at 5000 clicks/s from
      that at 40 clicks/s at a fixed stimulus level) were examined to compare how they
      separated the normally hearing and hearing impaired subjects. When compared to
      the results for both conventional and MLS linear or LNL TEOAEs, the present study
      found that the RNL results best reflected the patients' hearing loss, although
      the conventional linear and LNL responses performed nearly as well. Only two
      impaired ears (2%), both with a best threshold of 30 dB HL at 1000 Hz, produced
      RNL responses with amplitude within the range produced by 95% of the normal
      group.

PMID- 15855038
TI  - The influence of a sensitive period on central auditory development in children
      with unilateral and bilateral cochlear implants.
AB  - We examined the longitudinal development of the cortical auditory evoked
      potential (CAEP) in 21 children who were fitted with unilateral cochlear implants
      and in two children who were fitted with bilateral cochlear implants either
      before age 3.5 years or after age 7 years. The age cut-offs (<3.5 years for early
      implanted and >7 years for late-implanted) were based on the sensitive period for
      central auditory development described in [Ear Hear. 23 (6), 532.] Our results
      showed a fundamentally different pattern of development of CAEP morphology and P1
      cortical response latency for early- and late-implanted children. Early-implanted
      children and one child who received bilateral implants by age 3.5 years showed
      rapid development in CAEP waveform morphology and P1 latency. Late-implanted
      children showed aberrant waveform morphology and significantly slower decreases
      in P1 latency postimplantation. In the case of a child who received his first
      implant by age 3.5 years and his second implant after age 7 years, CAEP responses
      elicited by the second implant were similar to late-implanted children. Our
      results are consistent with animal models of central auditory development after
      implantation and confirm the presence of a relatively brief sensitive period for
      central auditory development in young children.

PMID- 15855039
TI  - Initial characterization of kinocilin, a protein of the hair cell kinocilium.
AB  - A subtracted library prepared from vestibular sensory areas [Nat. Genet. 26
      (2000) 51] was used to identify a 960bp murine transcript preferentially
      expressed in the inner ear and testis. The cDNA predicts a basic 124aa protein
      that does not share any significant sequence homology with known proteins.
      Immunofluorescence and immunoelectron microscopy revealed that the protein is
      located mainly in the kinocilium of sensory cells in the inner ear. The protein
      was thus named kinocilin. In the mouse, kinocilin is first detected in the
      kinocilia of vestibular and auditory hair cells at embryonic days 14.5, and 18.5,
      respectively. In the mature vestibular hair cells, kinocilin is still present in
      the kinocilium. As the auditory hair cells begin to lose the kinocilium during
      postnatal development, kinocilin becomes distributed in an annular pattern at the
      apex of these cells, where it co-localizes with the tubulin belt [Hear. Res. 42
      (1989) 1]. In mature auditory hair cells, kinocilin is also present at the level
      of the cuticular plate, at the base of each stereocilium. In addition, as the
      kinocilium regresses from developing auditory hair cells, kinocilin begins to be
      expressed by the pillar cells and Deiters cells, that both contain prominent
      transcellular and apical bundles of microtubules. By contrast, kinocilin was not
      detected in the supporting cells in the vestibular end organs. The protein is
      also present in the manchette of the spermatids, a transient structure enriched
      in interconnected microtubules. We propose that kinocilin has a role in
      stabilizing dense microtubular networks or in vesicular trafficking.

PMID- 15855040
TI  - Hyperprolactinemia in some Meniere patients even in the absence of incapacitating
      vertigo.
AB  - Stress can be a significant factor influencing ear pathologies and is often
      reported to trigger the symptoms of Meniere's disease. Both physiological and
      psychological stress provokes the release of prolactin from the pituitary thus
      allowing the classification of prolactin as a major stress hormone. We
      investigated the level of the stress hormone prolactin in a Swedish population
      with early symptoms of Meniere's disease. The median prolactin level in the
      Meniere patients (n=33) was not significantly different from that of non-Meniere
      patients (n=23). However, in the Meniere group one female (90 year old) had
      prolactin levels in the upper normal range for women, one male (77 year old) had
      prolactin levels above the normal limit for men, and a third patient (76 year old
      female) presented hyperprolactinemia with more than twice the normal level. MRI
      confirmed a pituitary adenoma in this patient. This study provides further
      support for the recent report of hyperprolactinemia in some patients with long
      standing Meniere's disease and presenting incapacitating vertigo in France. The
      data emphasize the likely implication of stress in this pathology where the
      stress hormone prolactin is likely to represent one actor in a complex hormonal
      imbalance affecting the inner ear.

PMID- 15855041
TI  - Synaptic transmission mediated by ionotropic glutamate, glycine and GABA
      receptors in the rat's ventral nucleus of the lateral lemniscus.
AB  - The synaptic pharmacology of the ventral nucleus of the lateral lemniscus (VNLL)
      was investigated in brain slices obtained from rats of 14-37 days old using
      intracellular recording techniques. Excitatory and inhibitory synaptic potentials
      (EPSPs and IPSPs) were elicited by electrical stimulation of the lemniscal
      pathway and recorded from neurons with five types of intrinsic firing patterns
      (onset, pause, adapting, regular and bursting types). Synaptic receptors that
      mediated the EPSPs and IPSPs were identified using AMPA, NMDA, GABA(A) and
      glycine receptor antagonists. The early/short EPSPs were mediated by AMPA
      receptors. The late/long EPSPs, encountered only in neurons of younger animals,
      were mediated by NMDA receptors. The IPSPs in most neurons were mediated by
      glycine receptors. In some neurons the IPSPs were mediated by GABA(A) receptors
      or both glycine and GABA(A) receptors. The temporal dynamics of fast AMPA EPSPs
      and glycinergic IPSPs were very similar. AMPA EPSPs and glycinergic (and/or
      GABAergic) IPSPs could be encountered in a single neuron. The results suggest
      that the VNLL not only relays incoming signals rapidly from the lower brainstem
      to the inferior colliculus, but also integrates excitatory and inhibitory inputs
      to modify and process auditory information.

PMID- 15855042
TI  - Taicatoxin inhibits the calcium-dependent slow motility of mammalian outer hair
      cells.
AB  - The effects of taicatoxin on the slow motility of isolated outer hair cells of
      guinea pig were studied in the experiments. Pretreatment with taicatoxin (0.19
      microM) was able to prevent both the cell shortening induced by high K(+) (50mM),
      and the cell elongation induced by ionomycin (10 microM). These effects of
      taicatoxin can be mimicked by pretreatment of cells with Ca(2+)-free medium on
      the slow motility in response to ionomycin or high K(+). Pretreatment with
      neither calcium channel blockers such as nifedipine (L-type blocker), omega
      conotoxin GVIA (N-type blocker), and omega-agatoxin IVA (P-type blocker); nor
      potassium channel blockers, such as tetraethylammonium chloride (TEA) and 3,4
      diaminopyridine (3,4-DAP) can antagonize the cell shortening effect induced by
      high K(+) and cell elongation induced by ionomycin. The calcium-imaging
      experiment indicated that taicatoxin, but not nifedipine, did prevent an increase
      of intracellular Ca(2+) level significantly induced by high K(+). These results
      demonstrate that the effect of taicatoxin was to block the calcium entry through
      calcium channels of cell membrane, without relative to its properties of
      potassium channel blockers. We conclude that taicatoxin-sensitive-calcium
      channels at least impart, play a significant role in the slow motility of outer
      hair cell.

PMID- 15855043
TI  - Regeneration of human auditory nerve. In vitro/in video demonstration of neural
      progenitor cells in adult human and guinea pig spiral ganglion.
AB  - Time lapse video recordings of cultured adult human and guinea pig spiral
      ganglion (hSG and gpSG) show that mitogen responsive progenitor/stem cells
      develop in the form of spheres that proliferate and differentiate into mature
      neurons and glia cells. Neurospheres, cultured with EGF and bFGF showed
      expression of nestin and incorporation of 5'-Bromo-2-deoxyuridine (BrdU). Newly
      formed BrdU labelled cells were positive for beta-tubulin, and also for GFAP
      demonstrating that neuronal cells were derived from a dividing population of
      progenitor cells. Dissociated spheres cultured either with glia cell line-derived
      neurotrophic factor (GDNF) or brain-derived neurotrophic factor (BDNF) and
      neurotrophin-3 (NT-3), induced differentiation of the progenitor cells. Video
      microscopy showed that neurons develop from subcultured spheres maintained for up
      to four weeks. Neurons showed fasciculation and migration with a speed of 10-30
      microm/h, and some cells had up to 6 mm long neurites coexpressing TrkB and TrkC
      receptors. Precise dissection suggests that the neurons formed are cochlea
      specific. The results suggest that the mammalian auditory nerve has the
      capability for self-renewal and replacement. Transplantation of progenitor cells
      together with established means to induce neural differentiation and fiber growth
      may facilitate strategies for better repair and treatment of auditory neuronal
      damage.

PMID- 15855044
TI  - Recovery of human compound action potential using a paired-click stimulation
      paradigm.
AB  - The recovery process from adaptation of the compound action potential (CAP) was
      studied using an equilevel paired click stimulation paradigm in humans with
      normal hearing. The CAP amplitude to the second click of paired clicks was
      normalized to the amplitude to the first click. The second-click CAP amplitude
      recovered as a function of interclick interval (ICI) between the first and the
      second click of a pair. A regression line fitted to the recovered amplitude data
      demonstrated the logarithmic function of the ICI. Full recovery times changed
      from 118 to 278 ms with increasing click intensity. The regression lines for
      higher click intensities exhibited two different slopes in two ICI ranges: from 3
      to 100 and 120 to 300 ms. We suppose that the CAP recovery for ICI <100 ms is
      attributable to both the relative refractoriness of auditory nerve and the short
      term adaptation mechanisms, while, for ICI >100 ms chiefly to the short-term
      adaptation mechanisms. The recovery process of the second-click CAP slowed with
      increasing intensity, which is a similar result to that obtained in the animal
      experiments by Parham et al. The input-output (I-O) curve of the second-click CAP
      amplitudes exhibited a different slopes above and below 60 dB normal hearing
      level (nHL). We assume that the mechanisms underlying this characteristic curve
      pattern differ from those for the I-O curve of the CAP in response to single
      click stimuli. We expect that investigating the CAP recovery in pathological ears
      will provide clinically useful information on cochlear synaptic function.

PMID- 15855045
TI  - Corticofugal modulation of directional sensitivity in the midbrain of the big
      brown bat, Eptesicus fuscus.
AB  - In our recent study of corticofugal modulation of collicular amplitude
      sensitivity of the big brown bat, Eptesicus fuscus, we suggested that the
      corticofugal modulation is based upon the best frequency (BF) differences and the
      relative amplitude sensitivity difference between collicular (IC) and cortical
      (AC) neurons but not the absolute amplitude sensitivity of IC and AC neurons. To
      show that corticofugal modulation is systematic and multiparametric, we studied
      corticofugal modulation of directional sensitivity in 89 corticofugally inhibited
      IC neurons in the same bat species under free field stimulation conditions. A
      neuron's directional sensitivity was expressed with the azimuthal range (AR) at
      50% below the maximum of each directional sensitivity curve and the best azimuth
      (BAZ) at which the neuron discharged maximally. Cortical electrical stimulation
      did not affect the directional sensitivity of 40 (45%) neurons with BF(IC-AC)
      differences of 7.3+/-4.4kHz but sharpened the directional sensitivity of other 49
      (55%) neurons with BF(IC-AC) differences of 2.3+/-1.8kHz. Corticofugal modulation
      sharpened directional sensitivity curves of IC neurons by decreasing the AR and
      shifting collicular BAZ toward cortical BAZ. The decrease in AR and the shift in
      BAZ increased significantly with AR(IC-AC) and BAZ(IC-AC) differences but not
      with absolute AR and BAZ of IC and AC neurons or BF(IC-AC) differences.
      Corticofual modulation also shifted collicular BF toward cortical BF. The shift
      in BF increased significantly with BF(IC-AC) differences but not with the BF of
      IC and AC neurons or BAZ shift. Consonant with our previous study, these data
      indicate that corticofugal modulation of collicular directional sensitivity is
      based on topographic projections between the IC and the AC and the difference in
      directional sensitivity but not the absolute directional sensitivity of IC or AC
      neurons.

PMID- 15855046
TI  - Tyrosine phosphorylation in mitochondria: a new frontier in mitochondrial
      signaling.
AB  - Mitochondria are multifunctional organelles that participate in a range of
      cellular processes such as energy production, proliferation, death, and
      senescence. The involvement of mitochondria in such distinct aspects of cell life
      requires the existence of an integrated system of signals that enter and exit the
      organelle according to the diverse needs of the cell. The recent discovery of
      several protein kinases and phosphatases that localize partially or predominantly
      inside mitochondria opens new perspectives into the regulation of these signals.
      This review focuses on tyrosine phosphorylation in mitochondria. A description of
      the protein tyrosine kinases and phosphatases which regulate this process along
      with the mitochondrial tyrosine-phosphorylated proteins identified to date is
      followed by a discussion of the possible involvement of tyrosine phosphorylation
      in mitochondrial signaling and future perspectives for developments in this
      emerging field.

PMID- 15855047
TI  - Mitochondrial dysfunction in cardiovascular disease.
AB  - Whereas the pathogenesis of atherosclerosis has been intensively studied and
      described, the underlying events that initiate cardiovascular disease are not yet
      fully understood. A substantial number of studies suggest that altered levels of
      oxidative and nitrosoxidative stress within the cardiovascular environment are
      essential in the development of cardiovascular disease; however, the impact of
      such changes on the subcellular or organellar components and their functions that
      are relevant to cardiovascular disease inception are less understood. In this
      regard, studies are beginning to show that mitochondria not only appear
      susceptible to damage mediated by increased oxidative and nitrosoxidative stress,
      but also play significant roles in the regulation of cardiovascular cell
      function. In addition, accumulating evidence suggests that a common theme among
      cardiovascular disease development and cardiovascular disease risk factors is
      increased mitochondrial damage and dysfunction. This review discusses aspects
      relating mitochondrial damage and function to cardiovascular disease risk factors
      and disease development.

PMID- 15855048
TI  - Role of peroxidases in Parkinson disease: a hypothesis.
AB  - Extensive research has been done to elucidate the underlying molecular events
      causing neurodegenerative diseases such as Parkinson disease, yet the cause and
      the individual steps in the progression of such diseases are still unknown. Here
      we advance the hypothesis that, rather than or in addition to inorganic radical
      molecules, heme-containing peroxidase enzymes may play a major role in the
      etiology of Parkinson disease. This hypothesis is based on the following
      considerations: (1) several heme-containing enzymes with peroxidase activity are
      present in the substantia nigra pars compacta; (2) these peroxidases have the
      ability to catalyze the oxidation of proteins and lipids; (3) certain heme
      peroxidases are known to destroy cells in vivo; (4) heme peroxidases have the
      stability and specificity that could account for the fact that specific molecules
      and cells are subject to damage in Parkinson disease, rather than a random
      destruction; (5) heme peroxidase activity could account for certain reactions in
      connection with parkinsonism that thus far have not been adequately explained;
      and (6) the participation of a heme peroxidase could explain some recent
      observations that are inconsistent with the oxyradical theory. The peroxidase
      catalyzed oxidative pathway proposed here does not preclude the participation of
      apoptosis as an additional mechanism for cell destruction.

PMID- 15855049
TI  - Hypoxia-reoxygenation-induced mitochondrial damage and apoptosis in human
      endothelial cells are inhibited by vitamin C.
AB  - Hypoxia and hypoxia-reperfusion (H-R) play important roles in human
      pathophysiology because they occur in clinical conditions such as circulatory
      shock, myocardial ischemia, stroke, and organ transplantation. Reintroduction of
      oxygen to hypoxic cells during reperfusion causes an increase in generation of
      reactive oxygen species (ROS), which can alter cell signaling, and cause damage
      to lipids, proteins, and DNA leading to ischemia-reperfusion injury. Since
      vitamin C is a potent antioxidant and quenches ROS, we investigated the role of
      intracellular ascorbic acid (iAA) in endothelial cells undergoing hypoxia
      reperfusion. Intracellular AA protected human endothelial cells from H-R-induced
      apoptosis. Intracellular AA also prevents loss of mitochondrial membrane
      potential and the release of cytochrome C and activation of caspase-9 and caspase
      3 during H-R. Additionally, inhibition of caspase-9 activation prevented H-R
      induced apoptosis, suggesting a mitochondrial site of initiation of apoptosis. We
      found that H-R induced an increase in ROS in endothelial cells that was abrogated
      in the presence of iAA. Our results indicate that vitamin C prevents hypoxia and
      H-R-induced damage to human endothelium.

PMID- 15855050
TI  - Oxidative stress precedes peak systemic inflammatory response in pediatric
      patients undergoing cardiopulmonary bypass operation.
AB  - Oxidative stress seems to contribute to cardiopulmonary bypass (CPB)-related
      postoperative complications. Pediatric patients are particularly prone to these
      complications. With this in mind, we measured oxidative stress markers in blood
      plasma of 20 children undergoing elective heart surgery before, during, and up to
      48 h after cessation of CPB, along with inflammatory parameters and full analysis
      of iron status. Ascorbate levels were decreased by approximately 50% (P < 0.001)
      at the time of aorta cross-clamp removal (or pump switch-off in 4 patients with
      partial CPB), and associated with corresponding increases in dehydroascorbate (P
      < 0.001, r = -0.80) and malondialdehyde (P < 0.01, r = -0.59). In contrast to the
      immediate oxidative response, peak levels of IL-6 and IL-8 were not observed
      until 3-12 h after CPB cessation. The early loss of ascorbate correlated with
      duration of CPB (P < 0.002, r = 0.72), plasma hemoglobin after cross-clamp
      removal (P < 0.001, r = 0.70), and IL-6 and IL-8 levels at 24 and 48 h after CPB
      (P < 0.01), but not with postoperative lactate levels, strongly suggesting that
      hemolysis, and not inflammation or ischemia, was the main cause of early
      oxidative stress. The correlation of ventilation time with early changes in
      ascorbate (P < 0.02, r = 0.55), plasma hemoglobin (P < 0.01, r = 0.60), and
      malondialdehyde (P < 0.02, r = 0.54) suggests that hemolysis-induced oxidative
      stress may be an underlying cause of CPB-associated pulmonary dysfunction.
      Optimization of surgical procedures or therapeutic intervention that minimize
      hemolysis (e.g., off-pump surgery) or the resultant oxidative stress (e.g.,
      antioxidant treatment) should be considered as possible strategies to lower the
      rate of postoperative complications in pediatric CPB.

PMID- 15855051
TI  - Glutathione depletion inhibits lipopolysaccharide-induced intercellular adhesion
      molecule 1 synthesis.
AB  - Cellular redox status is known to regulate a number of biological processes,
      including the activation of inflammatory genes. Our previous studies demonstrated
      that thiol depletion using diethyl maleate (DEM) reduced neutrophil sequestration
      in animal models of inflammation, an effect primarily mediated by impaired
      upregulation of the adhesion molecule, ICAM-1. The present studies were performed
      to discern the mechanism whereby DEM prevents LPS-induced ICAM-1 expression in
      human umbilical vein endothelial cells. DEM caused a time- and concentration
      dependent inhibition of ICAM-1 expression in LPS-stimulated HUVEC by blocking
      induction of gene transcription. Interestingly, DEM had little effect on the
      degradation of the inhibitory protein IkappaB-alpha, but rather appeared to
      prevent translocation of the transcription factor NF-kappaB into the nucleus.
      Readdition of glutathione following DEM treatment restored the ability of LPS to
      induce NF-kappaB translocation and ICAM-1 synthesis. DEM plus LPS caused
      synergistic induction of heme oxygenase-1 (HO-1), suggesting its role in the
      inhibitory effects of DEM. However, HO-1 was shown to be neither sufficient nor
      necessary for the anti-inflammatory effects of glutathione depletion. These
      studies illustrate that thiol depletion may represent a potential therapy for
      inflammation, exerting its effects via a distinct mechanism on cell signaling
      pathways.

PMID- 15855052
TI  - Redox regulation of the transcriptional repressor Bach1.
AB  - Bach1 is a transcriptional repressor of heme oxygenase-1, one of the most
      inducible phase 2 proteins. Bach1 binds in conjunction with a small Maf protein
      to tandem repeats of the antioxidant response element (ARE) and quenches the
      target gene expression. On the other hand, the transactivator Nrf2 binds and up
      regulates the ARE-governed gene expression. By using a sulfhydryl oxidizing
      agent, diamide, here we provide evidence which indicates that the Bach1 function
      is regulated by the redox state. Diamide showed restricted Nrf2 nuclear
      translocation and ARE-driven reporter activity but reversed the ARE
      transcriptional activity suppressed by ectopically expressed Bach1. Substitution
      of the conserved cysteine residue in the DNA binding domain of Bach1 to serine
      (C574S mutant) caused a refractory response to the diamide-mediated reactivation
      of the Bach1-suppressed reporter activity. Moreover, diamide induced cytoplasmic
      translocation of the GFP-Bach1 fusion protein but failed to translocate the
      fusion protein consisting of the C574S mutant. These data suggest that redox
      regulation of Bach1 is an alternative mechanism to induce multiple ARE-governed
      genes.

PMID- 15855053
TI  - Differential apoptotic and redox regulatory activities of curcumin and its
      derivatives.
AB  - We have synthesized different bioconjugates of curcumin, which were tested for
      their pro- and antioxidant properties. In the present study five representative
      derivatives of curcumin, i.e., 4,4'-di-(O-acetyl) curcumin, 4,4'-di-(O-glycinoyl)
      curcumin, 4,4'-di-(O-glycinoyl-di-N-piperoyl) curcumin, 4,4'-di-(O-piperoyl)
      curcumin, and 4,4'-(O,O-cystinoyl)-3,3'-dimethoxydiphenyl-1,6-heptadiene-3,5
      dione, were used for testing their apoptotic potential on tumor cells. Dipiperoyl
      and diglycinoyl derivatives showed higher apoptotic activity at lower
      concentrations, whereas diacetyl curcumin had slightly lower apoptotic activity
      on tumor cells. On the other hand, diglycinoyl-dipiperoyl and cystinoyl
      heptadiene derivatives had lost their apoptotic potential significantly. The
      apoptotic activity of these derivatives correlated very well with the generation
      of ROS by the tumor cells, whereas GSH levels remained unaltered. Our studies
      also indicate downregulation of Bcl-2 and participation of caspase-3 in the
      apoptotic death of tumor cells.

PMID- 15855054
TI  - Nitric oxide-induced resistance to hydrogen peroxide stress is a glutamate
      cysteine ligase activity-dependent process.
AB  - Nitric oxide (*NO) is a reactive nitrogen species known to be involved in
      cytotoxic processes. Cells respond to cytotoxic injury by stress response
      induction leading to the development of cellular resistance. This report
      describes an *NO-induced stress response in Chinese hamster fibroblasts (HA1),
      which leads to glutathione synthesis-dependent resistance to H2O2-mediated
      oxidative stress. The development of resistance to H2O2 was completely abolished
      by the inhibition of glutamate cysteine ligase (GCL) during the first 8 h of
      recovery after *NO exposure. Altered thiol metabolism was observed immediately
      after *NO exposure as demonstrated by up to 75% decrease in intracellular thiol
      pools (glutathione, gamma-glutamylcysteine, and cysteine), which then
      reaccumulated during the *NO-mediated development of resistance. Immunoreactive
      protein and activity associated with GCL decreased immediately after exposure to
      *NO and then reaccumulated during the development of resistance to H2O2
      challenge. Moreover, compared to N2 controls the activity levels of GCL in *NO
      exposed cells increased approximately twofold 24 h after H2O2 challenge. These
      results demonstrate that *NO exposure is capable of inducing an adaptive response
      to H2O2-mediated oxidative stress in mammalian cells, which involves alterations
      in thiol metabolism and is dependent upon glutathione synthesis and increased GCL
      activity.

PMID- 15855055
TI  - Lipid peroxidation during ischemia depends on ischemia time in warm ischemia and
      reperfusion of rat liver.
AB  - Prolonged hepatic warm ischemia has been incriminated in oxidative stress after
      reperfusion. However, the magnitude of oxidative stress during ischemia has been
      controversial. The aims of the present study were to elucidate whether lipid
      peroxidation progressed during ischemia and to clarify whether oxidative stress
      during ischemia aggravated the oxidative damage after reperfusion. Rats were
      subjected to 30 to 120 min of 70% warm ischemia alone or followed by reperfusion
      for 60 min. Lipid peroxidation (LPO) was evaluated by amounts of
      phosphatidylcholine hydroperoxide (PC-OOH) and phosphatidylethanolamine
      hydroperoxide (PE-OOH) as primary LPO products. Total amounts of malondialdehyde
      and 4-hydroxy-2-nonenal (MDA + 4-HNE), degraded from hydroperoxides, were also
      determined. PC-OOH and PE-OOH significantly increased at 60 and 120 min ischemia
      with concomitant increase of oxidized glutathione. These hydroperoxides did not
      increase at 60 min reperfusion after 60 min ischemia, whereas they did increase
      at 60 min reperfusion after 120 min ischemia with deactivation of phospholipid
      hydroperoxide glutathione peroxidase and superoxide dismutase. The amount of MDA
      + 4-HNE exhibited similar changes, but the velocity of production dropped with
      ischemic time longer than 60 min. In conclusion, oxidative stress progressed
      during ischemia and triggered the oxidative injury after reperfusion. Secondary
      LPO products are less sensitive, especially during ischemia, which may cause
      possible underestimation and discrepancy.

PMID- 15855056
TI  - Antioxidant up-regulation and increased nuclear DNA protection play key roles in
      adaptation to oxidative stress in epithelial cells.
AB  - Cells are armed with a vast repertoire of antioxidant defense mechanisms to help
      prevent the accumulation of oxidative damage. It is becoming increasingly
      apparent that the cellular adaptive response has an important antioxidant
      function to counteract oxidative stress. To investigate this adaptive response we
      assessed the effect of sublethal H2O2 on cell viability, enzymatic activity, and
      nuclear (nDNA) and mitochondrial DNA (mtDNA) susceptibility to damage and repair
      in cultured human retinal pigment epithelium (RPE) cells. This nondividing cell
      type exists in a highly oxidizing microenvironment in vivo. Prior exposure to
      sublethal H2O2 confirmed an adaptive response, resulting in a greater cellular
      resistance to subsequent toxic exposures compared to nonadapted RPE (p < 0.05). A
      greater CAT, GPX, and CuZnSOD enzymatic activity (p < 0.05) and increased nDNA
      protection (p < 0.05) were also observed. However, there was no adaptive benefit
      for mtDNA protection or repair in response to oxidative stress. This study
      confirms a role for the adaptive response as an important antioxidant defense for
      cells located in inherently oxidizing microenvironments. Furthermore, it
      identifies that the mitochondria are a weak link in otherwise efficient oxidative
      stress defenses and that this may contribute to aging and age-related disease.

PMID- 15855057
TI  - Analysis of differentially expressed genes in nitric oxide-exposed human
      monocytic cells.
AB  - In this study we examined the gene expression pattern of *NO-dependent genes in
      U937 and Mono Mac 6 monocytes exposed to the synthetic NO-donor DPTA-NO using
      microarray technology. cDNA microarray data were validated by Northern blot
      analysis and quantitative real-time PCR. This approach allowed the identification
      of 17 *NO-sensitive genes that showed at least a twofold difference in
      expression, in both U937 cells and Mono Mac 6 cells exposed to 500 microM DPTA-NO
      for 4 h. NO-stimulated genes belong to various functional groups, including
      transcription factors, signaling molecules, and cytokines. Among the selected
      genes, 11 (ATF-4, c-maf, SGK-1, PBEF, ATPase 8, NADH dehydrogenase 4, STK6, TRAF4
      associated factor 1, molybdopterin synthase, CKS1, and CIDE-B) have not been
      previously reported to be sensitive to *NO. Because several *NO-stimulated genes
      are transcription factors, we analyzed the mRNA expression profile in U937 cells
      exposed to DPTA-NO for 14 h. We found that long-term *NO treatment influenced
      transcription rates of a rather limited set of genes, including CIDE-B, BNIP3,
      p21/Cip1, molybdopterin synthase, and TRAF4-associated factor 1. To accelerate
      formation of nitrosating species, U937 cells were exposed to DPTA-NO along with
      suboptimal concentrations of 2-phenyl-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide
      (PTIO). PTIO-mediated increase in nitrosating species remarkably enhanced *NO
      dependent induction of IL-8, p21/Cip1, and MKP-1 and built a specific gene
      expression profile.

PMID- 15855058
TI  - Vitamin E differentially regulates the expression of peroxiredoxin-1 and -6 in
      alveolar type II cells.
AB  - Vitamin E is the primary lipophilic antioxidant in mammals. Lack of vitamin E may
      lead to an increase of cytotoxic phospholipid-peroxidation products (PL-Ox).
      However, we could previously show that alimentary vitamin E-depletion in rats did
      not change the concentrations of dienes, hydroperoxides, and platelet-activating
      factor-related oxidation products in alveolar type II cells (TII cells). We
      hypothesized that vitamin E deficiency increases the activity of enzymes involved
      in the degradation of PL-Ox. Degradation of PL-Ox may be catalyzed by
      phospholipase A2, PAF-acetylhydrolase, or peroxiredoxins (Prx's). Alimentary
      vitamin E deficiency in rats increased the expression of Prx-1 at the mRNA and
      protein levels and the formation of Prx-SO3, but it did not change the expression
      of Prx-6 or the activity of phospholipase A2 and PAF-acetylhydrolase in TII
      cells. H2O2-induced oxidative stress in isolated TII cells activated protein
      kinase Calpha (PKCalpha) and increased the expression of Prx-1 and Prx-6.
      Inhibition of PKCalpha in isolated TII cells by long-time incubation with PMA
      inhibited PKCalpha and Prx-1 but not Prx-6. We concluded that the expression of
      Prx-1 and -6 is selectively regulated in TII cells; PKCalpha regulates the
      expression of Prx-1 but not Prx-6. Prx-6 expression may be closely linked to
      lipid peroxidation.

PMID- 15855059
TI  - Detection of intracranial hemorrhage: comparison between gradient-echo images and
      b0 images obtained from diffusion-weighted echo-planar sequences on 3.0T MRI.
AB  - In this study, we compared the effectiveness of b0 echo-planar MR images (EPI)
      imaging with gradient recalled echo (GRE) in detecting acute hemorrhage. Brain
      images in 69 patients who suffered from acute infarction were reviewed. Nine of
      them had suffered from acute hemorrhage. Comparing b0EPI and GRE images side-by
      side, we found no significant different effectiveness in detecting hemorrhage (P
      = .522, > or =.05). We concluded that b0EPI imaging could detect hemorrhagic
      lesions as effectively as GRE can without additional acquisition time.

PMID- 15855060
TI  - Diffusion and magnetization transfer MRI of brain infarct, infection, and tumor
      in children.
AB  - The purpose of this study was to determine the efficacy of diffusion-weighted
      imaging (DWI) and magnetization transfer imaging (MTI) in the differential
      diagnosis of brain infarct, infection, hamartoma, and tumor in 106 children. The
      apparent diffusion coefficients (ADCs) and magnetization transfer ratios (MTRs)
      of the lesions were compared using nonparametric tests. There was an inverse
      relationship between ADC and MTR in subacute/chronic infarct, infection,
      hamartoma, arachnoid cyst, and tumor relative to normal brain parenchyma. Both
      ADC and MTR were reduced in acute infarct. DWI and MTI had a complementary role
      in the differential diagnosis of acute infarct from infection with lower MTR,
      from hamartoma with higher ADC, and from low-grade gliomas and benign tumors that
      had higher ADCs and lower MTRs. ADCs increased and MTRs decreased with the
      duration of infarct and lower tumor grade.

PMID- 15855061
TI  - Low-dose multidetector dynamic CT in the breast: preliminary study.
AB  - This study investigated the feasibility of using low-dose multidetector dynamic
      computed tomography (CT) scan for imaging breast. We measured the radiation dose
      using a phantom at low- and standard-dose CT. To compare the image quality at low
      and standard-dose CT, we evaluated normal breasts in 57 cases. In 44 cases with
      breast cancer, we assessed the staging and time-enhancement curves of breast
      cancer. In conclusion, the low-dose multidetector dynamic CT scan is feasible for
      the evaluation of the breast, with reduced radiation dose and with similar image
      quality when compared with standard-dose CT scan. In breast cancers, low-dose
      dynamic CT could be used for the staging of breast cancer before surgery.

PMID- 15855062
TI  - Support vector machines in sonography: application to decision making in the
      diagnosis of breast cancer.
AB  - We evaluated a series of pathologically proven breast tumors using the support
      vector machine (SVM) in the differential diagnosis of solid breast tumors. This
      study evaluated two ultrasonic image databases, i.e., DB1 and DB2. The DB1
      contained 140 ultrasonic images of solid breast nodules (52 malignant and 88
      benign). The DB2 contained 250 ultrasonic images of solid breast nodules (35
      malignant and 215 benign). The physician-located regions of interest (ROI) of
      sonography and textual features were utilized to classify breast tumors. An SVM
      classifier using interpixel textual features classified the tumor as benign or
      malignant. The receiver operating characteristic (ROC) area index for the
      proposed system on the DB1 and the DB2 are 0.9695+/-0.0150 and 0.9552+/-0.0161,
      respectively. The proposed system differentiates solid breast nodules with a
      relatively high accuracy and helps inexperienced operators avoid misdiagnosis.
      The main advantage in the proposed system is that the training procedure of SVM
      was very fast and stable. The training and diagnosis procedure of the proposed
      system is almost 700 times faster than that of multilayer perception neural
      networks (MLPs). With the growth of the database, new ultrasonic images can be
      collected and used as reference cases while performing diagnoses. This study
      reduces the training and diagnosis time dramatically.

PMID- 15855063
TI  - Radiological appearance of postirradiation sarcoma of the chest wall after
      mastectomy.
AB  - Radiotherapy-induced sarcoma arising from the chest wall after mastectomy and
      irradiation is uncommon but deserves special attention due to the increasing
      incidence of this soft-tissue sarcoma, contributed by the early detection and
      employment of radiotherapy in the treatment of breast carcinoma. We report the
      computed tomography (CT) and magnetic resonance imaging (MRI) features of two
      patients who developed cutaneous high-grade sarcoma after mastectomy and
      irradiation for primary breast tumours more than 5 years ago.

PMID- 15855064
TI  - Sonographically guided core biopsy of the salivary gland masses: safety and
      efficacy.
AB  - Over an 8-year period, we performed ultrasonography (US)-guided core biopsy of
      the salivary gland in 37 patients using an 1l-mm-throw 18-gauge automated biopsy
      system. The biopsy results were retrospectively compared with the findings of
      surgical pathology (n=18) or more than 6 months of clinical follow-up (n=19). The
      sensitivity, specificity, and accuracy of US-guided core biopsy for the diagnosis
      of malignancy were 75.0%, 96.6%, and 91.9%, respectively. No immediate or delayed
      complications occurred.

PMID- 15855065
TI  - CT colonography using different reconstruction modi.
AB  - OBJECTIVE: Performing computed tomography (CT) colonography, we compared
      different reconstruction modi for the detection of colorectal polyps. METHODS:
      The CT data of 48 patients using 16-slice helical CT were analysed in axial
      slices, virtual-endoscopy and colon-dissection modus. RESULTS: The sensitivity
      (specificity) for the detection of colonic polyps was 94% (80%) if using "colonic
      dissection" tool and 89% (80%) if using "virtual-endoscopy" tool. The difference
      between the virtual endoscopy and colon dissection, considering polyps up to 4.9
      mm, was significant. CONCLUSIONS: Reconstruction software colon dissection
      improves the sensitivity of CT colonography.

PMID- 15855066
TI  - CT colonography features of sigmoid diverticular disease.
AB  - OBJECTIVE: The objective of this study is to assess the sigmoid distensibility
      during CT colonography (CTC) in patients with diverticular disease. METHODS:
      Consecutive patients without a history of pelvic radiation or neoplasms underwent
      150 CTC. Three radiologists in consensus evaluated axial images for colonic
      distention, luminal diameters (mm), diverticula, and muscular thickening.
      RESULTS: The minimum colon diameter in patients with muscular thickening was
      significantly smaller, irrespective of the presence of diverticula (P=.009).
      CONCLUSION: Muscular thickening with diverticular disease was associated with
      significantly less sigmoid colon distension.

PMID- 15855067
TI  - Carcinoid tumor of the ampulla of Vater. Magnetic resonance imaging findings.
AB  - Carcinoid tumors arising from the ampulla of Vater are rare, and their magnetic
      resonance (MR) imaging findings have not been reported in the literature to date.
      We report a case of carcinoid tumor of the ampulla of Vater and discuss the
      characteristic MR imaging findings. The tumor was isointense relative to the
      muscle on both the T1- and T2-weighted images with heterogeneous enhancement
      after gadolinium administration. Both the common bile and the pancreatic ducts
      were dilated on the MR cholangiopancreatography.

PMID- 15855068
TI  - Transforaminal periradicular infiltration guided by CT for unilateral sciatica-
      an outcome study.
AB  - Selective transforaminal periradicular infiltration with local corticosteroids
      and anesthetics has been performed for preoperative evaluation of lumbosacral
      pain and for patients with sciatia. From July 2001 to November 2003, 143 patients
      with unilateral sciatica were treated with computed tomography (CT)-guided
      transforaminal periradicular infiltration. Needle puncture was possible without
      difficulty in all patients. Of all 143 infiltrations, 140 were followed up with
      the recovery of leg and back pain and improvement of the straight leg-raising
      test (SLRT). Minor complications were seen, but major complications and mortality
      did not occur in our series. In summary, CT guidance allows safe and precise
      needle positioning, and it can readily demonstrate the spread of the medications
      in the exact periradicular space.

PMID- 15855069
TI  - Neuropsychiatric systemic lupus erythematosus: correlation of brain MR imaging,
      CT, and SPECT.
AB  - Systemic lupus erythematosus (SLE) patients frequently present with
      neuropsychiatric symptoms. We conducted an imaging study with magnetic resonance
      (MR) imaging, computed tomography (CT), and single photon emission CT (SPECT) in
      23 patients with SLE, 13 with major neuropsychiatric symptoms (NPSLE) and 10
      without (non-NPSLE). The most frequent brain imaging findings were seen with MR
      imaging and were more prevalent in NPSLE: high signal intensity focal white
      matter lesions, infarcts in the cortex and pons, and basal ganglia lesions.

PMID- 15855070
TI  - Learning the ropes together: assimilation and friendship development among first
      year male medical students.
AB  - This study explores the mutual influences of friendship development and
      organizational assimilation processes among first-year male medical students.
      Interviews and observations were used to examine the ways students constructed
      and enacted their friendships with male classmates during the process of
      assimilating into medical school. The study also examined how the male friends
      viewed the influence of their friendships on their assimilation into medical
      school and how the assimilation process simultaneously influenced their
      developing friendships. Thematic analysis revealed that although the men
      perceived their medical school friendships as "not yet close," the friendships
      provided them with valuable tangible and socio-emotional support during the
      rigorous assimilation process and that the assimilation process paradoxically
      facilitated as well as hindered the development of friendships. Implications for
      practice and future research are discussed.

PMID- 15855071
TI  - Telling it like it is: the adaptive function of narratives in coping with loss in
      later life.
AB  - As the population ages, caregivers and health care providers need more insight
      into how people experience old age and their attitudes and emotions about growing
      older. It is particularly critical to understand how communication processes
      change and how older adults communicate their concerns and feelings. This article
      proposes that some discursive activities may play a crucial role in successfully
      adapting to, and coping with, loss in later life. Thus, this study explored how
      older adults reflect on and express themselves concerning recent experiences of
      loss. A sample of 41 residents of 2 independent-living retirement communities
      wrote in journals about a recent significant loss. Participants wrote about their
      losses during brief lab sessions over the course of 3 consecutive days. Each set
      of 3 journals was content-analyzed to measure the frequency with which the
      participants employed emotional expression, factual recounting, account giving,
      religious-account giving, humor, intensifiers, and referential statements. The
      analysis indicates that, overall, participants shifted from a primarily factual
      mode (what the loss was, how the loss occurred, etc.) to more of a focus on the
      impact of this loss on their lives (e.g., handling new tasks and expressions of
      emotions) over the 3 sessions. In addition, most participants offered accounts of
      their losses; that is, they attempted to find some meaning in the loss and
      integrate the loss into an overall framework for their lives. Many of these
      accounts focused on religion. Final sections of the article discuss the
      implications of journaling as a mechanism for effective coping with loss, as a
      useful tool for expressing emotions, and as a means for older adults' caregivers
      and health care providers to better adapt their supportive messages.

PMID- 15855072
TI  - Life without TV? cultivation theory and psychosocial health characteristics of
      television-free individuals and their television-viewing counterparts.
AB  - Much attention has been paid to the amount of time Americans spend watching
      television. Cultivation theory has been important in exploring behavioral effects
      of television viewing for many years. However, psychosocial health has received
      much less scrutiny in relation to television viewing time. This investigation
      examined the hypotheses that television-free individuals and viewers adhering to
      the American Academy of Pediatrics (AAP) recommendations (up to 2 hr of viewing
      per day) would display a more positive psychosocial health profile when compared
      with more frequent television viewers. Results confirmed the hypothesis for
      women, but not for men. Our analysis showed that moderate television viewing, as
      defined by the AAP, provides a similar relation with psychosocial health as being
      television-free. Results are discussed in a cultivation theory framework.

PMID- 15855073
TI  - Using formative evaluation to improve a smoking cessation intervention for
      pregnant women.
AB  - Triangulation analysis was used to assess qualitative data collected to examine
      smoking cessation materials and methods prior to a large randomized clinical
      trial with pregnant smokers. The patient education program's components were
      tested with 265 patients receiving Medicaid-insured care in 9 public clinics. The
      formative evaluation process conducted during this pilot study of the Smoking
      Cessation and Reduction in Pregnancy Trial included assessment of A Pregnant
      Woman's Guide to Stop Smoking (Windsor et al., 2002), a companion video, clinic
      reinforcement, and patient-centered counseling. Focus groups were conducted, with
      23 (82%) of the nurses and social workers who provided the intervention. Twenty
      nine (20.8%) of the women who received the intervention were interviewed
      individually. The qualitative data were examined to identify convergence and
      divergence among and between providers and patients about presentation, use of
      components, and program impact. Findings were used to refine the intervention to
      enhance patient and staff receptivity, specifically to ensure participant
      comprehension and shorten time required of busy staff.

PMID- 15855074
TI  - It's the product: do risky products compel attention and elicit arousal in media
      users?
AB  - This article reports on two studies designed to measure whether the mere presence
      of a risky product in a mediated message (separate from executional elements of
      the message) elicits greater attention and arousal in media users. In the first
      study, participants viewed and rated 30 pictures of risky (alcohol, tobacco,
      drugs, condoms) and nonrisky (soda, juice, food) products while heart rate and
      skin conductance were measured. In the second study, participants viewed and
      rated 30 risky and nonrisky product words while the same measures were recorded.
      Results showed that the risky pictures and words elicited more emotional and
      physiological arousal than nonrisky pictures and words. Risky pictures elicited
      different orienting responses than nonrisky pictures, but there was no difference
      in orienting for risky and nonrisky words. Both risky pictures and words were
      remembered better than nonrisky pictures and words. The results of this study
      suggest that the mere presence of the representation of a risky product (either
      pictorial or verbal) elicits more arousal and more memory but not more attention
      in media users.

PMID- 15855075
TI  - Authoritative parenting and drug-prevention practices: implications for antidrug
      ads for parents.
AB  - This research employed the theory of reasoned action to investigate the role of
      authoritative parenting in 3 drug-prevention behaviors: (a) parental monitoring,
      (b) parent-child discussions, and (c) awareness of the child's environment. A
      phone survey of 158 parents of adolescents in 7th, 9th, and 11th grades revealed
      that authoritative parenting was correlated with parenting practices that reduce
      the likelihood of adolescent drug use, including discussing family rules about
      drugs, discussing strategies to avoid drugs, discussing those in trouble with
      drugs, parental monitoring, knowing the child's plans for the coming day, and
      personally knowing the child's friends well. Additionally, authoritative
      parenting moderated the attitude-behavioral intention relation for parental
      monitoring and awareness of the child's environment, with the weakest relation
      detected for low-authoritative parents. The utility of these findings in helping
      design and target antidrug messages for parents more effectively is discussed.

PMID- 15855076
TI  - Bibliography.

PMID- 15855077
TI  - U.S. health care policy and the rising uninsured: an alternative solution.
AB  - The lack of adequate health insurance affects one's ability to access care, which
      directly affects one's health. In the 21st century, there are 44 million people
      in the United States without health care insurance. The majority of people
      without health care insurance are working people under age 65, because most
      people over age 65 are retired and have health insurance through the federal
      Medicare program. Maintaining a healthy population makes good business sense
      because healthy people are more able to work, buy goods, and pay taxes that
      contribute to a healthy economy and strong government. We must understand,
      through provider "cost shifting," the American public is already "footing the
      bill" for the uninsured. However, the actual amount is hidden and passed on to
      consumers in payments to insurance companies through raised premiums,
      deductibles, co-payments, exclusions from coverage, and direct out-of-pocket
      payments to providers (e.g., physicians, hospitals). Ironically, the very working
      poor who are uninsured and underinsured help fund the health insurance of select
      federally protected groups through taxation. A huge gap exists in the current
      United States system of health care wherein there is no cogent benefit, only a
      vicious cycle as the insured continue to pay more for their care to help
      compensate provider losses due to the uninsured. This in turn causes a growing
      rank of uninsured individuals that lack access to adequate health care. The
      purpose of this article is to assert an alternative to the current U.S. health
      care insurance system. It takes advantage of structures already in place to
      promote a "win-win" American health system premised on a workable tiered
      universal health care system in which there is a benefit to the major populace.
      As an emanation of a diverse society, the proposed system does not advocate a one
      payer universal system that is not amenable to the U.S. health care, social, or
      political environment.

PMID- 15855078
TI  - Discrimination of gays and lesbians: a social justice perspective.
AB  - The existence of discrimination against America's gay and lesbian citizens is
      widely supported in the research literature of many disciplines. This article
      provides a specific analysis of this discrimination and demonstrates the stark
      contrast between the discrimination of gays and lesbians in American society and
      the social justice concepts of equality and fairness. The works of Rawls, and
      later the works of Nussbaum, provide the theoretical framework highlighting the
      factors related to this discrimination and inequality. In the concluding section,
      specific implications for future policy development are presented that are
      designed to ensure that gays and lesbians are not further discriminated against.
      Areas examined include civil unions, gay marriages, adoptions, hate crime
      legislation and cessation of the U.S. military's "Don't Ask, Don't Tell, Don't
      Pursue" policy, advocating for inclusion of open gays and lesbians in military
      positions and commandership.

PMID- 15855079
TI  - Unfinished business: Radiation Exposure Compensation Act (RECA) for post-1971
      U.S. uranium underground miners.
AB  - Congress enacted the Radiation Exposure Compensation Act (RECA) in 1990 and
      amended it in 2000. Included for compensation were underground uranium miners who
      developed health problems related to radiation exposures. Neither the 1990 Act
      nor the 2000 Amendments covered post-1971 workers. In this article, we will
      examine regulatory history and scientific evidence used for the passage of RECA
      for the pre-1972 miners and will present evidence supporting the inclusion of the
      post-1971 workers.

PMID- 15855080
TI  - A comprehensive snapshot of States' small group market reforms on insurer pricing
      & rating practices, 1999.
AB  - This paper presents a qualitative analysis of states' small group health
      insurance reforms that impact small group premiums, mostly enacted by the states
      during 1996-99, following the federal Health Insurance Portability and
      Accountability Act in 1996. It draws from an intensive review of statutes of 48
      states and the District of Columbia as of 1999. It analyses regulations related
      to insurer pricing and rating practices concerning rating criteria and rating
      bands, pricing incentives, premium stability from year to year, minimum loss
      rations, reinsurance and carve-out coverage for the medically uninsurable. It
      also covers regulations targeting employer purchasing and coverage practices such
      as pooled purchasing and adverse selection. This is the second of a two-part
      series analyzing states' small group market reforms, the first being devoted to
      state reforms to promote access and improving the value of health plans offered
      in this market (Xirasagar et al. 2004). The variety in pricing and rating reforms
      illustrate the differences in the depth of reforms across states, and represent a
      far wider range of potential actuarial combinations than the sample of reforms
      documented in past literature.

PMID- 15855081
TI  - PET/CT unplugged: the merging technologies of PET and CT imaging.
AB  - OBJECTIVE: This article discusses the current and potential issues physicians are
      facing as PET/CT is integrated into medical practice. CONCLUSION: A variety of
      issues related to PET/CT were discussed at the 2004 ARRS annual meeting. Among
      the conclusions were that both PET and CT portions of a PET/CT scan need to be
      reviewed for adequate patient care, and that nuclear medicine should not be
      exempt from current self-referral legislation.

PMID- 15855082
TI  - Issues, controversies, and clinical utility of combined PET/CT imaging: what is
      the interpreting physician facing?
AB  - OBJECTIVE: This article identifies the most commonly encountered issues of
      combined PET/CT and shows the wide variability in perceived possible solutions to
      these issues. This article will serve as a catalyst to stimulate discussion
      between experts in both radiology and nuclear medicine. CONCLUSION: Combining a
      PET tomography and CT scanner into a single unit amounts to advantages that are
      not merely additive, but synergistic. Even PET/CT skeptics will embrace the
      technology after becoming acquainted with the possibilities and will accept the
      reality that there is no return to PET only.

PMID- 15855083
TI  - Establishing a PET/CT practice.
AB  - OBJECTIVE: This chapter discusses the differences in the operation of dual
      technique PET/CT compared with conventional PET tomography in clinical practice.
      CONCLUSION: Although PET/CT still is a relatively new medical imaging technique,
      it is becoming the preferred method for body oncology imaging and will play an
      increasingly important role in molecular imaging in clinical practice. Therefore,
      it is imperative that facilities learn how to establish a successful PET/CT
      practice.

PMID- 15855084
TI  - The business of PET/CT.
AB  - OBJECTIVE: This chapter discusses how to market to and educate the referral
      community and third party payers about the benefits of the emerging PET/CT
      technology. CONCLUSION: Clearly, the fusion of PET and CT into one piece of
      equipment will present challenges for years to come. It is important for
      providers to be involved with all of the administrators, managers, referring and
      interpreting physicians, and the payer communities in their market to clearly
      understand individual payer business practices and to identify opportunities to
      educate and influence changes in payment and coverage policies.

PMID- 15855085
TI  - Reader agreement studies.

PMID- 15855086
TI  - Performance-based assessment of radiology faculty: a practical plan to promote
      improvement and meet JCAHO standards.
AB  - OBJECTIVE: The objective of this article is to describe the process of
      implementing a program for performance-based assessment of clinical faculty.
      CONCLUSION: A performance-based assessment of clinical faculty program
      facilitated quality improvements in our department, improved communication
      concerning our reappointment process, and was well received by faculty. The
      presence of measures on a scorecard stresses what is important for clinical care
      and facilitates process improvement in these areas. Having practitioner-specific
      data compiled in an organized fashion helps meet the standards of the Joint
      Commission on Accreditation of Healthcare Organizations (JCAHO).

PMID- 15855087
TI  - MDCT evaluation of the coronary arteries, 2004: how we do it--data acquisition,
      postprocessing, display, and interpretation.
AB  - OBJECTIVE: Cardiac CT is rapidly becoming part of clinical practice. The
      objective of this article is to discuss and illustrate the current practice of
      coronary artery MDCT, including data acquisition, postprocessing, image display,
      and interpretation. The practice described reflects our experience with a series
      of patients referred in routine clinical practice. CONCLUSION: The reader should
      gain an insight into the current clinical application of coronary artery CT.

PMID- 15855088
TI  - ECG-gated 16-MDCT of the coronary arteries: assessment of image quality and
      accuracy in detecting stenoses.
AB  - OBJECTIVE: The aim of this study was to investigate image quality and diagnostic
      accuracy in detecting coronary artery lesions using a 16-MDCT scanner. MATERIALS
      AND METHODS: Thirty-seven patients (28 men, nine women) underwent unenhanced
      helical CT and MDCT angiography of the coronary arteries. After patients received
      oral beta-blocker medication, CT scans were obtained during a single breath-hold
      with a 16-MDCT scanner using ECG-gating (0.75-mm collimation, 2.8-mm table
      feed/rotation, 0.42-sec rotation time). The image quality was assessed in terms
      of artifacts and segment visibility by two reviewers. Stenosis severity was
      compared with the results of conventional invasive coronary angiography. RESULTS:
      The data evaluation of the image quality was based on a total of 488 segments, of
      which 380 segments were considered to have diagnostic image quality. One hundred
      eight segments (22.1%) could not be sufficiently evaluated because of severe
      calcifications (35 segments) and motion artifacts (73 segments). The mean calcium
      score (Agatston score equivalent [ASE]) was 524.3 +/- 807.6. Twenty-eight (75.7%)
      of the 37 patients had an ASE of less than 1,000 (mean ASE, 90.8 +/- 152.3 [SD]),
      and nine (24.3%) patients had an ASE of 1,000 or greater (mean ASE, 1,761.0 +/-
      637.6). For detecting lesions 50% or greater (without any exclusion criteria),
      the overall sensitivity, specificity, positive predictive value, and negative
      predictive value were 59%, 87%, 61%, and 87%, respectively. When limiting the
      number of patients to those with a calcium score of less than 1,000 ASE, the
      threshold-corrected sensitivity for lesions 50% or greater was 93%; specificity,
      94%; positive predictive value, 68%; and negative predictive value, 99%.
      CONCLUSION: In patients with no or moderate coronary calcification, MDCT of
      coronary arteries using 16-MDCT technology allows the reliable detection of
      coronary artery stenoses with high diagnostic accuracy. Obtaining an initial
      unenhanced scan was found to be mandatory to avoid performing useless
      examinations in patients with severe calcifications.

PMID- 15855089
TI  - Myocardial late enhancement in contrast-enhanced cardiac MRI: distinction between
      infarction scar and non-infarction-related disease.
AB  - OBJECTIVE: Our objective was to assess and compare the patterns of late
      enhancement (LE) in contrast-enhanced cardiac MRI caused by myocardial infarction
      and different myocardial diseases that are not related to ischemic infarction.
      MATERIALS AND METHODS: A total of 811 consecutive contrast-enhanced cardiac MRI
      studies performed for different indications were reviewed for left ventricular
      myocardial LE after gadopentetate dimeglumine administration. MRI studies were
      performed on a 1.5-T scanner using an inversion recovery turbo FLASH sequence
      (TR/TE, 8/4 msec; flip angle, 25 degrees). The LE pattern of ischemic infarction
      scar was compared with that in nonischemic myocardial disease. RESULTS: LE was
      found in 421 (52%) patients. In all patients with myocardial infarction, LE
      included the subendocardial layer. Nineteen patients without history of
      myocardial infarction and angiographically excluded coronary artery disease
      showed different patterns of LE caused by myocarditis, sarcoidosis,
      arrhythmogenic right ventricular dysplasia, cardiomyopathy, endomyocardial
      fibrosis, and iatrogenic scars after biopsy, ablation of septal hypertrophy, and
      myocardial laser revascularization. CONCLUSION: LE in contrast-enhanced cardiac
      MRI is not specific for ischemic infarction. LE in ischemic infarction always
      involves the subendocardial layer, whereas it does not necessarily do so in other
      myocardial diseases. Therefore, if LE omit the subendocardial layer, different
      nonischemic myocardial diseases have to be considered. The pattern of LE might be
      helpful for the differential diagnosis of myocardial disease and in
      distinguishing it from ischemic disease.

PMID- 15855090
TI  - Delayed contrast-enhanced MRI of the aortic wall in Takayasu's arteritis: initial
      experience.
AB  - OBJECTIVE: Delayed contrast-enhanced MRI is increasingly being used for cardiac
      viability imaging. Takayasu's arteritis is a rare inflammatory disorder of
      unknown cause that affects the aorta, its major branches, and the pulmonary
      artery; it is characterized by inflammation and fibrosis in the arterial wall. We
      report our initial experience with seven patients (six women, one man; age range,
      25-62 years) with delayed (20 min) gadolinium-enhanced MRI (inversion recovery
      prepared gated fast gradient-echo pulse sequence) in patients with known
      Takayasu's arteritis. CONCLUSION: Patients with Takayasu's arteritis
      (particularly those with abnormal laboratory values) have evidence of delayed
      hyper-enhancement on delayed contrast-enhanced MRI. Thus, delayed contrast
      enhanced MRI might be a useful technique to identify inflammation in arterial
      wall.

PMID- 15855091
TI  - Endomyocardial fibrosis and intracardiac thrombus occurring in idiopathic
      hypereosinophilic syndrome.

PMID- 15855092
TI  - Aortosternal venous compression in patients with aberrant right subclavian
      arteries.

PMID- 15855093
TI  - Individually adapted examination protocols for reduction of radiation exposure
      for 16-MDCT chest examinations.
AB  - OBJECTIVE: The purpose of our study was to develop a simple protocol for
      reduction of radiation exposure without loss of diagnostic information in chest
      16-MDCT. MATERIALS AND METHODS: Two hundred and four patients underwent MDCT of
      the thorax (Somatom Sensation 16, Siemens). Group 1 was scanned using a standard
      protocol with 100 mAs(effective) (mAs(eff)). Group 2 was scanned using a dose
      modulation template (CareDose). Group 3 was scanned with mAs(eff) = body weight
      (kg). Group 4 was scanned with a combination of weight-adapted mAs(eff) and dose
      modulation. All other parameters were kept constant. Signal-to-noise ratio was
      assessed as an objective measurement for image quality, and subjective image
      quality was rated by three experienced radiologists on a 4-point scale. Effective
      dose was calculated using dedicated software. RESULTS: The mean noise measurement
      values were 8.31 H for the 100 mAs(eff) protocol for the regression between
      weight and signal-to-noise (p < 0.0001), 9.08 H for group 2 (p < 0.0001), 9.0 H
      for group 3 (p = 0.5051), and 9.98 H for group 4 (p = 0.0152). The median image
      quality was 1 (1 = highest quality) in all subgroups. The mean effective dose was
      6.83 mSv, 5.92 mSv, 4.73 mSv, and 3.97 mSv, respectively. The least correlation
      between weight and image noise was achieved for the individually weight-adapted
      protocol and in the weight-adapted with CareDose combination. CONCLUSION: By tube
      current time product adaptation (kg = mAs(eff)) combined with an online tube
      current modulation template, a well-balanced examination without significant loss
      of information was achieved for this specific scanner. Thus, individually adapted
      protocols for chest 16-MDCT can be recommended.

PMID- 15855094
TI  - Dynamic CT evaluation of the central airways in patients undergoing tracheoplasty
      for tracheobronchomalacia.
AB  - OBJECTIVE: The objective of this study was to describe the role of pre- and
      postoperative dynamic CT in patients undergoing tracheoplasty, a novel surgical
      method for treatment of severely symptomatic tracheobronchomalacia. CONCLUSION:
      Five patients were referred for dynamic MDCT before and after undergoing
      tracheoplasty at our institution. Preoperatively, all patients showed signs of
      tracheobronchomalacia (> or = 50% airway collapse) on bronchoscopy, and four
      (80%) of these five patients showed evidence of malacia on dynamic forceful
      expiratory CT scans. In all five cases, postoperative CT showed a reduction in
      the degree of airway collapse during expiration, changes in shape of the trachea
      during inspiration, and posterior wall thickening related to the procedure. Our
      preliminary results suggest a potentially important role for CT in the pre- and
      postoperative assessments of patients with tracheobronchomalacia referred for
      tracheoplasty.

PMID- 15855095
TI  - Rapid musculoskeletal MRI with phase-sensitive steady-state free precession:
      comparison with routine knee MRI.
AB  - OBJECTIVE: The aim of this work was to show the potential utility of a novel
      rapid 3D fat-suppressed MRI method for joint imaging. CONCLUSION: Phase-sensitive
      steady-state free precession provides rapid 3D joint imaging with robust fat
      suppression and excellent cartilage delineation.

PMID- 15855096
TI  - Surgically repaired massive rotator cuff tears: MRI of tendon integrity, muscle
      fatty degeneration, and muscle atrophy correlated with intraoperative and
      clinical findings.
AB  - OBJECTIVE: Our goal in this study was to evaluate by means of MRI the clinical
      significance of tendon integrity, muscle fatty degeneration, and muscle atrophy
      in surgically repaired massive rotator cuff tears and to correlate these and
      other prognostic factors with intraoperative and clinical findings. MATERIALS AND
      METHODS: Twenty-eight surgically proven massive rotator cuff tears were
      retrospectively included in the study. Twenty-two patients underwent complete
      repair, and six patients underwent partial repair. Preoperative and postoperative
      clinical assessment was performed by using the University of California at Los
      Angeles score. Preoperative and postoperative MRI studies were evaluated for the
      presence and extent of rotator cuff tear and for the degree of fatty degeneration
      and atrophy of the rotator cuff muscles. RESULTS: At a mean 44.4 months' follow
      up, 20 patients (71.4%) had a favorable result. A total of 25 patients (89.2%)
      showed postoperative full-thickness rotator cuff tear, 19 of which were
      reruptures. A sagittal preoperative rotator cuff tear of less than or equal to 34
      mm showed a specificity of 100% for predicting a favorable outcome. A coronal
      postoperative rotator cuff tear of less than or equal to 34 mm showed a
      specificity of 85.7% and a positive predictive value of 92.9% for predicting a
      favorable outcome. A postoperative fatty degeneration of infraspinatus muscle
      less than or equal to 2 had a specificity of 87.5% and a positive predictive
      value of 90.9% for predicting a favorable outcome. CONCLUSION: Open repair of
      massive rotator cuff tears may reach a favorable outcome in a significant
      proportion of patients, despite a high rate of recurrent or residual tears.
      Oblique coronal sizes of the recurrent or residual tear of less than or equal to
      34 mm and postoperative fatty degenerations of infraspinatus muscle of less than
      or equal to 2 may allow a favorable outcome.

PMID- 15855097
TI  - Lunate chondromalacia: evaluation of routine MRI sequences.
AB  - OBJECTIVE: Chondromalacia is a commonly encountered abnormality at arthroscopy
      and may be responsible for significant clinical symptoms and disability. In the
      wrist, the most common location for chondromalacia is the lunate bone.
      Consequently, we sought to study the accuracy of clinical MRI in the assessment
      of lunate articular cartilage. MATERIALS AND METHODS: MR images of 34 patients
      who underwent arthroscopy and had an MRI examination within 1 month of surgery
      were evaluated by two reviewers for the presence and location of lunate cartilage
      defects and subchondral edema. RESULTS: Lunate cartilage defects were seen on MRI
      in 10 of the 13 patients with chondromalacia, but these defects were also
      incorrectly noted in three of 21 of patients without chondromalacia. The visible
      locations for cartilage defects were the ulnar aspect of the proximal lunate bone
      (n = 3), radial aspect of the proximal lunate bone (n = 4), ulnar aspect of the
      distal lunate bone (n = 2), and radial aspect of the distal lunate bone (n = 1).
      Subchondral marrow edema was observed in six of the 10 patients with
      chondromalacia seen on MRI; in all six patients, the edema was seen in the same
      quadrant as the cartilage defect. Marrow edema was detected in one patient
      without chondromalacia. CONCLUSION: We conclude that lunate chondromalacia can be
      accurately assessed using routine MRI sequences, although there are occasional
      false-positive interpretations.

PMID- 15855098
TI  - 16-MDCT in the detection of occult wrist fractures: a comparison with skeletal
      scintigraphy.
AB  - OBJECTIVE: Our objective was to assess the potential use of MDCT in the detection
      of occult scaphoid fractures. Fifty-one patients with suspected radiographically
      occult scaphoid fractures at 10-14 days after trauma were investigated
      prospectively with skeletal scintigraphy and CT on the same day. Planar images of
      the wrist were taken 3 hr after IV injection of 400 MBq of (99m)Tc-methylene
      diphosphonate using a single-head gamma camera. CT was performed on a 16-MDCT
      machine using 0.75-mm detectors and reconstruction in 0.5-mm slices. Multiplanar
      reformatted images were then viewed in interactive cine mode. The examinations
      were reported independently, and discordant results were compared at follow-up.
      CT was positive for wrist fracture in 14 (27.4%) of 51 patients and skeletal
      scintigraphy in 23 (45.1%) of 51 patients. Even after retrospective review, there
      were seven discrepant cases (13.7%), all of which were positive for wrist
      fracture on scintigraphy but negative on CT. Four of these seven patients with
      discordant findings underwent further radiography at 6 weeks, which did not show
      fracture. CONCLUSION: Although CT was preferred by most patients and was quicker,
      scintigraphy appears to detect bony abnormality more frequently. However, there
      appears to be an interesting group of patients (7/51) with normal initial
      radiography findings but positive scintigraphy findings who would normally be
      considered to have a fracture but for whom CT results were negative. In some of
      these patients, the results of follow-up radiography at 6 weeks were also
      negative, suggesting that this group of patients warrants further study.

PMID- 15855099
TI  - MRI of spring ligament tears.
AB  - OBJECTIVE: Surgical repair of the spring ligament is becoming recognized as an
      important management component of adult-acquired flatfoot, yet little literature
      exists on the MRI appearance of spring ligament abnormalities. In this article,
      we describe the MRI appearance of surgically proven spring ligament tears.
      CONCLUSION: MRI findings present in surgically proven spring ligament tears
      include an abnormal spring ligament caliber, signal intensity, waviness, a full
      thickness gap, and posterior tibial tendonopathy. The finding unique to cases
      with surgically proven tears is a full-thickness gap in the ligament, seen in 79%
      of the cases in our series. When multiple abnormalities are seen in the spring
      ligament in conjunction with a full-thickness gap, the diagnosis of a tear can be
      made with confidence.

PMID- 15855100
TI  - Skimboarder's toe: findings on high-field MRI.
AB  - OBJECTIVE: Our purpose is to report hyperdorsiflexion injuries of the
      metatarsophalangeal joints associated with the sport of skimboarding and to
      describe the MRI appearance of these injuries. CONCLUSION: Skimboarding can be
      associated with hyperdorsiflexion injuries of the metatarsophalangeal joint. MRI
      shows that such injuries are associated with hyperdorsiflexion of the extensor
      hallucis longus or extensor digitorum longus tendon, causing tear of the extensor
      expansion. Unlike turf toe, in which the plantar plate is involved, skimboarder's
      toe involves structures dorsal to the metatarsophalangeal joint.

PMID- 15855101
TI  - MRI appearance of chondral delamination injuries of the knee.
AB  - OBJECTIVE: We describe the MRI appearance of five cases of chondral delamination
      of the knee. CONCLUSION: Chondral delamination injuries of the knee show
      increased linear signal abnormality at the junction of the articular cartilage
      and subchondral bone on T2-weighted (fast spin-echo) images of the knee.
      Identifying and treating these lesions results in an improved prognosis for
      patients with this injury.

PMID- 15855102
TI  - MRI of the rotator interval capsule.

PMID- 15855103
TI  - Plastic deformation of the femur: cross-sectional imaging.

PMID- 15855104
TI  - MR quantification of the washout changes in breast tumors under preoperative
      chemotherapy: feasibility and preliminary results.
AB  - OBJECTIVE: The objective of our study was to describe and determine the
      feasibility of an MR washout quantification method in patients with breast cancer
      under preoperative chemotherapy. MATERIALS AND METHODS: Nineteen patients with
      breast T2 or T3 tumors were enrolled in a previous study for tumor response
      evaluation during chemotherapy based on dynamic contrast-enhanced MRI. We
      retrospectively used the dynamic acquisition data to produce parametric images
      representing the washout pattern. Two radiologists unaware of the final
      pathologic results measured the volume of pixels exhibiting washout within the
      tumor before chemotherapy (volume 1), after two courses of chemotherapy (volume
      2), and before surgery after four courses of chemotherapy (volume 3). The
      interobserver variability and intraobserver variability were calculated to
      evaluate the reproducibility of our method with the Pearson's correlation
      coefficient and the concordance correlation coefficient. We correlated the
      washout changes by means of a Student's t test and noted the histopathologic
      final outcome. RESULTS: A washout pattern was present in all patients on the
      initial MR study. The quantification method of the washout changes was
      reproducible with good interobserver agreement (r = 0.85, p < 10(-5)) and an
      excellent intraobserver agreement (r = 0.94, p < 10(-5)). A significant decrease
      of the washout volume was observed after two courses of chemotherapy (p = 0.004),
      whereas no significant modification was observed between two and four courses of
      chemotherapy (p = 0.52). CONCLUSION: Quantification of the washout variation in
      breast tumor based on the use of parametric images is feasible and reproducible.
      It may add information to the evaluation of tumor response to preoperative
      therapy.

PMID- 15855105
TI  - Is maximum positive predictive value a good indicator of an optimal screening
      mammography practice?
AB  - OBJECTIVE: Positive predictive value (PPV1) has been used as one important
      indicator of the quality of screening mammography programs. We show how the
      relationship between sensitivity and recall rate may affect the operating point
      at which optimal (maximum) PPV1 occurs. CONCLUSION: Optimal (maximum) PPV1 can
      occur at any sensitivity level and should not be used as the sole indicator for
      practice optimization because it does not take into account the number of cancers
      that would be missed at that sensitivity.

PMID- 15855106
TI  - Screening mammography reduces morbidity of breast cancer treatment.
AB  - OBJECTIVE: This commentary discusses the retrospective cohort study by Barth et
      al. studying the effect of screening mammography on morbidity of breast cancer
      treatment. CONCLUSION: Barth et al. found that cancers identified at screening
      mammography (versus those detected by physical examination) were smaller and more
      frequently node-negative. Hence, the former group of breast cancer patients was
      more likely to be treated with less morbid therapy. This evidence-based study
      contributes to the clinical practice of screening mammography.

PMID- 15855107
TI  - Determination of splenomegaly by CT: is there a place for a single measurement?
AB  - OBJECTIVE: Our objective was to determine if there is a single parameter that can
      be used as a marker of splenomegaly using CT. MATERIALS AND METHODS: Splenic
      length, width, and thickness were measured in 249 CT scans and multidimensional
      indexes were obtained from the multiplication of these measurements. Volume was
      calculated by summing the volumes of multiple contiguous scans. The relationship
      of the spleen to the left liver lobe and inferior third of the left kidney was
      also evaluated. Linear equations were obtained to correlate each measurement to
      the splenic volume. RESULTS: The unidimensional measurements with best
      correlation to volume were splenic length (r = 0.81, p < 0.01) and width (r =
      0.804, p < 0.01). Correlation was better for the multidimensional indexes (r =
      0.95, p < 0.01). Using a previously described upper limit of normality for
      splenic volume of 314.5 cm3 in the linear regression equation obtained, a maximum
      spleen length of 9.76 cm was the upper limit of normality. The relation of the
      lowest point of the spleen to the inferior third of the kidney also showed that
      if the spleen reached or extended below this portion of the kidney, it could be
      used as evidence of splenomegaly (p < 0.005), although it had a low sensitivity.
      CONCLUSION: Splenic length and multidimensional indexes correlate well with
      splenic CT volume. A splenic length of 9.76 cm can be used to accurately diagnose
      splenomegaly and can replace multiple-measurement, time-consuming methods in the
      clinical routine.

PMID- 15855108
TI  - Individual modulation of the tube current-seconds to achieve similar levels of
      image noise in contrast-enhanced abdominal CT.
AB  - OBJECTIVE: Our aim was to determine the optimal region to measure CT image noise
      and to evaluate the usefulness of the individual modulation of the tube current
      second (milliampere-seconds, or mAs) based on body size to obtain images with
      similar noise levels. MATERIALS AND METHODS: Contrast-enhanced abdominal CT
      images obtained by a 4-MDCT scanner were retrospectively analyzed. The image
      acquisition factors were fixed (group A, n = 104). The image noise was measured
      at five regions: the aorta, the back muscle, the spleen, and the peripheral and
      the central hepatic portions. Body size was evaluated by two methods on the basis
      of body weight (method A) and on the scout image data (method B). Coefficients of
      determination of 10 relationships between body size and image noise were
      calculated. For the next study, CT images were prospectively obtained by
      modulating the mAs on the basis of body weight (group B, n = 100) and the scout
      image data (group C, n = 100). We compared the differences in SDs of aortic image
      noise in each group using the F test. RESULTS: The coefficients of determination
      of the aorta were 0.619 and 0.812 for methods A and B, respectively, and the
      highest values in both methods (p = (1/5)(2), Fisher's exact test). The SDs of
      the aortic image noise of groups A, B, and C were 2.03, 1.61, and 1.06,
      respectively. There were statistically significant differences between each group
      (p < 0.022), and the SD was the smallest in group C. CONCLUSION: The aorta was
      the optimal region to measure the image noise. Individual mAs modulation based on
      the scout image data was useful to obtain images of similar noise levels.

PMID- 15855109
TI  - Tailgut cyst: MRI evaluation.
AB  - OBJECTIVE: The purpose of our study was to evaluate the MRI features of tailgut
      cysts in five patients. CONCLUSION: Our results suggest that MRI may be useful in
      the diagnosis of tailgut cyst. A multilocular cystic mass in the presacral space
      is a characteristic MRI finding of tailgut cyst, which may also be revealed as a
      cystic mass consisting of a large cyst accompanied by a small peripheral cyst.
      However, further studies are necessary to establish the usefulness of MRI for
      evaluating tailgut cysts.

PMID- 15855110
TI  - Intraoperative sonogram in mesenteric revascularization: spectrum of findings.
AB  - OBJECTIVE: The role of intraoperative sonography is to detect and prompt revision
      of technical defects that may adversely affect results. Our objective is to
      describe the technique and illustrate normal and abnormal findings in
      intraoperative sonography of mesenteric revascularization. CONCLUSION: An
      abnormality on a gray-scale image associated with hemodynamic changes is a
      significant finding. Awareness and recognition of major abnormalities should
      prompt immediate surgical revision and improved outcome.

PMID- 15855111
TI  - Combined transmesocolic-transomental internal hernia.

PMID- 15855112
TI  - MDCT of hypervascular hepatocellular carcinomas: a prospective study using
      contrast materials with different iodine concentrations.
AB  - OBJECTIVE: The objective of our study was to investigate the effect of different
      iodine concentrations in contrast materials on the depiction of hypervascular
      hepatocellular carcinomas (HCCs) by MDCT. SUBJECTS AND METHODS: This prospective
      study involved 100 consecutive patients with chronic liver disease, including 27
      patients with hypervascular HCCs. The first 50 patients received 100 mL of
      iopamidol at a concentration of 370 mg I/mL (group A) and the subsequent 50, 100
      mL at 300 mg I/mL (group B); in both groups, the contrast material was
      administered at a rate of 3.0 mL/sec. Unenhanced scanning and four-phase enhanced
      scanning at 25, 40, 60, and 180 sec after the start of contrast injection were
      performed. The enhancement of the aorta, liver, and portal vein was measured
      during each phase. In addition, tumor-to-liver contrast was calculated for the 27
      patients with hypervascular HCCs. Of the 27 patients with hypervascular HCCs, 15
      were in group A and 12 were in group B. RESULTS: During all phases, aortic
      enhancement was significantly greater in group A than group B (p < 0.01). Hepatic
      enhancement was significantly greater in group A than group B at 60 and 180 sec
      (both p < 0.01). There was no significant difference in hepatic enhancement
      between the two groups at 25 and 40 sec. Tumor-to-liver contrast was
      significantly greater in group A than group B during the late arterial phase (40
      sec, p = 0.02), although there was no significant difference at 25, 60, and 180
      sec. CONCLUSION: Contrast materials with higher iodine concentration are more
      effective for depicting hypervascular HCCs on MDCT during the late arterial
      phase.

PMID- 15855113
TI  - MRI findings of focal eosinophilic liver diseases.
AB  - OBJECTIVE: The purpose of this study was to describe the MRI findings of focal
      eosinophilic infiltration and eosinophilic abscess of the liver. CONCLUSION: MRI
      shows characteristic findings of focal eosinophilic liver disease that can be
      helpful in differentiating lesions of focal eosinophilic liver disease from other
      focal liver lesions. In addition, eosinophilic abscess and focal eosinophilic
      infiltration showed different MRI findings from each other.

PMID- 15855114
TI  - Hepatic artery pseudoaneurysms in adult living-donor liver transplantation:
      efficacy of CT and Doppler sonography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy of contrast
      enhanced CT and Doppler sonography in the diagnosis of hepatic artery
      pseudoaneurysm after adult living-donor liver transplantation (LDLT). CONCLUSION:
      Because patients with hepatic artery pseudoaneurysm after LDLT can have diverse
      clinical presentations, routine imaging follow-up is important for early
      detection. Although Doppler sonography is limited in showing the pseudoaneurysm,
      contrast-enhanced CT, especially MDCT with CT arteriography, is effective in
      showing it in most patients.

PMID- 15855115
TI  - MR cholangiography with manganese dipyridoxyl diphosphate in the evaluation of
      biliary-enteric anastomoses: preliminary experience.
AB  - OBJECTIVE: The purpose of our study was to assess the usefulness of manganese
      dipyridoxyl diphosphate (Mn-DPDP)-enhanced T1-weighted MR cholangiography for
      evaluating patients with biliary-enteric anastomoses. CONCLUSION: Mn-DPDP
      enhanced T1-weighted MR cholangiography may provide useful functional information
      and may aid in the assessment of the patency of biliary-enteric anastomoses.

PMID- 15855116
TI  - Functional MR cholangiography: diagnosis of functional abnormalities of the
      gallbladder and biliary tree.
AB  - OBJECTIVE: Our objective was to describe the technique and utility of functional
      MR cholangiography (fMRC) in the evaluation of the gallbladder and biliary tree.
      CONCLUSION: FMRC has the potential to provide a comprehensive examination for the
      anatomic and functional assessment of the gallbladder and biliary tree. Complex
      anatomic abnormalities and functional disorders can be shown by fMRC, including
      biliary obstruction and extravasation.

PMID- 15855117
TI  - Hilar and suprapancreatic cholangiocarcinoma: value of 3D angiography and
      multiphase fusion images using MDCT.
AB  - OBJECTIVE: We evaluated the feasibility of creating 3D and multiphase fusion
      images of cholangiocarcinoma. The 3D rendering of the biliary tree provide
      valuable information for planning surgery, including the location of the
      obstruction and its relationship to the surrounding vessels. CONCLUSION: Our data
      emphasize that 3D and multiphase fusion images may be an accurate and routinely
      applicable tool for the diagnosis and therapeutic management of patients with
      biliary system abnormalities.

PMID- 15855118
TI  - Delayed enhancement pattern in a localized fibrous tumor of the liver.

PMID- 15855119
TI  - Adenomatous polyp obscured by small-caliber rectal catheter at low-dose CT
      colonography: a rare diagnostic pitfall.

PMID- 15855120
TI  - Phlebosclerotic colitis: imaging findings of a rare entity.

PMID- 15855121
TI  - Radiologic findings of segmental testicular infarction.
AB  - OBJECTIVE: Our objective was to describe the radiologic findings of segmental
      testicular infarction and to establish a proper diagnosis that can avoid
      orchiectomy. CONCLUSION: The presence of a triangular-shaped avascular
      intratesticular lesion on sonography or MRI and enhancement of the surrounding
      borders on enhanced MR images may suggest a presurgical diagnosis of segmental
      testicular infarction and therefore avoid a total orchiectomy in these patients.

PMID- 15855122
TI  - CT voiding cystourethrography using 16-MDCT for the evaluation of female urethral
      diverticula: initial experience.

PMID- 15855123
TI  - Nonneoplastic hyperdense enhancing renal mass: CT findings and pathologic
      correlation.

PMID- 15855124
TI  - Retroperitoneal ectopic pregnancy.

PMID- 15855125
TI  - Imaging of transposed ovaries in patients with cervical carcinoma.
AB  - OBJECTIVE: Lateral ovarian transposition is a surgical procedure performed in
      premenopausal women with pelvic malignancies in which the ovaries are surgically
      displaced from the pelvis, before radiation therapy. In this article, we present
      the imaging features of normal transposed ovaries as well as the spectrum of
      abnormalities associated with lateral ovarian transposition. CONCLUSION: After
      lateral ovarian transposition, it is important to recognize the ovaries to avoid
      confusing them with peritoneal implants. In addition, benign ovarian lesions must
      be distinguished from primary and secondary malignancies.

PMID- 15855126
TI  - Comparison of effective doses for low-dose MDCT and radiographic examination of
      sinuses in children.
AB  - OBJECTIVE: Our objective was to show that in low-dose MDCT of the sinuses in
      children the effective dose can be lowered to a level comparable to that used for
      standard radiographic images, with resultant CT scans that are still of
      diagnostic image quality. MATERIALS AND METHODS: In standard radiographic
      examinations of sinuses (anteroposterior and lateral views) with 75 kV, 20 mAs,
      and 3-mm aluminum filtration in 69 children (mean age, 4.2 years), the dose-area
      product (DAP; mGy x cm2) was measured and converted to effective dose (mSv)
      according to coefficients published by the British National Radiological
      Protection Board. Another group of 125 children (mean age, 6.8 years) underwent
      low-dose MDCT of the sinuses with 6- or 16-MDCT in two phases and with different
      scanning protocols. An effective dose for MDCT was calculated from conversion of
      the dose-length-product (DLP, mGy xm) according to age. RESULTS: The mean
      effective dose (E) for standard radiography was 0.0528 mSv. The mean E value for
      low-dose MDCT was 0.096 mSv in the first phase of the study but could be lowered
      in the second phase to 0.0531 mSv by a combination of higher pitch and faster
      scan rotation time in our scan protocols, which results in diagnostic image
      quality at a very low dose. Statistical analysis showed no significant
      differences in effective dose between radiography and MDCT of the second phase.
      CONCLUSION: With modern MDCT technology, low-dose CT of the sinuses in children
      can yield diagnostic image quality using an effective dose comparable to that
      used for standard radiography.

PMID- 15855127
TI  - Role of imaging in management of hemophilic patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of symptomatology
      and conventional radiographic scoring in predicting synovial hypertrophy, which
      could affect the clinical management of hemophilic patients. MATERIALS AND
      METHODS: Twenty males (mean age, 14.3 years old) with hemophilic arthropathy,
      including 34 symptomatic joints and 26 asymptomatic joints (16 knees, 20 ankles,
      and 24 elbows) had conventional radiographs of individual joints obtained that
      were rated according to the Arnold-Hilgartner stage and the Pettersson score. The
      patients also underwent MRI for the detection of synovial hypertrophy. The
      association of synovial hypertrophy and symptomatology was evaluated using the
      chi-square or Fisher's exact test. The best sensitivity, specificity, and
      positive and negative predictive values in detection of synovial hypertrophy
      using symptomatology and radiographic scoring were calculated. RESULTS: A
      significant association was seen between symptomatology and synovial hypertrophy
      of the knee and ankle joints (p < 0.05). The sensitivity, specificity, and
      positive and negative predictive values of symptomatology in detection of
      synovial hypertrophy of the knee were 100%, 78%, 78%, and 100%, respectively, and
      for the ankle were 83%, 75%, 83%, and 75%, respectively. The Arnold-Hilgartner
      stage and Pettersson score of the radiograph had a significant association with
      synovial hypertrophy of the knee and ankle joints (p < 0.05). Arnold-Hilgartner
      staging provided a better prediction of synovial hypertrophy, with sensitivity,
      specificity, positive predictive value, and negative predictive value of 100%,
      100%, 100%, and 100% for knees and 82%, 100%, 100%, and 82% for ankles.
      CONCLUSION: In hemophilic patients, the presence of symptomatology in the knee
      and ankle joints is associated with synovial hypertrophy, and scoring of the
      conventional radiographs using Arnold-Hilgartner staging is useful for the
      prediction of synovial hypertrophy.

PMID- 15855128
TI  - Phosphorus-31 MR spectroscopy in pediatric liver transplant recipients: a
      noninvasive assessment of graft status with correlation with liver function tests
      and liver biopsy.
AB  - OBJECTIVE: Noninvasive in vivo hepatic phosphorus-31 MR spectroscopy has recently
      been shown to provide information about hepatic functional status. We sought to
      show the correlation of phosphorus-31 MR spectroscopy with blood biochemistry and
      liver biopsy results in pediatric patients after liver transplantation. MATERIALS
      AND METHODS: Eleven pediatric transplant recipients (eight with good graft
      function, two with chronic hepatitis, and one with acute rejection) and four
      healthy control subjects were studied with in vivo 31P MR spectroscopy. Ratios of
      phosphomonoesters (PME) to total phosphorus (TP), phosphodiester (PDE) to TP,
      nucleotide triphosphates (NTP), inorganic phosphate (Pi), and intracellular acid
      base status (pH) were measured. Liver function test (n = 11) and biopsy (n = 3)
      results were obtained for correlation with spectroscopic findings. RESULTS: The
      eight patients with good graft function displayed spectral profiles similar to
      those of the healthy subjects, and no significant difference in the metabolic
      ratios of these patients compared with the control subjects was detected. Three
      patients with abnormal liver function and biopsy-proven hepatic complications
      showed elevated PME/TP ratios when compared with those of both the control
      subjects and the group with good graft function. CONCLUSION: Phosphorus-31 MR
      spectroscopy is a feasible technique for the noninvasive assessment of host
      related complications in pediatric patients after liver transplantation. Our
      preliminary data suggest that the technique may be integrated with MRI for the
      investigation of impaired liver function in transplant recipients when neither a
      biliary complication nor a vascular complication is identified.

PMID- 15855129
TI  - High-resolution renal sonography in children with autosomal recessive polycystic
      kidney disease.
AB  - OBJECTIVE: Our objective was to describe the spectrum of renal findings using a
      high-frequency linear array transducer in patients with autosomal recessive
      polycystic kidney disease (ARPKD). CONCLUSION: There is a spectrum of findings in
      the kidney in patients with ARPKD that is very well depicted using the high
      resolution technique described in this article.

PMID- 15855130
TI  - Incomplete double aortic arch with atresia of the distal left arch: distinctive
      imaging appearance.
AB  - OBJECTIVE: We present 10 patients with double aortic arch with atresia of the
      distal left arch segment, a form of incomplete double aortic arch, and describe
      the distinct MRI and CT findings for this potentially symptomatic vascular ring.
      CONCLUSION: Knowledge of the distinctive imaging appearance of this congenital
      arch anomaly can direct the radiologist to the correct preoperative diagnosis.

PMID- 15855131
TI  - Congenital dislocation of the patella.
AB  - OBJECTIVE: Our objective was to present the imaging findings for congenital
      dislocation of the patella, an uncommon condition with variable clinical
      manifestations in patients of different ages. CONCLUSION: Sonography can clearly
      illustrate the presence and location of the laterally displaced patella and the
      anatomy of adjacent joint structures. The high resolution for soft-tissue,
      cartilaginous, and bony structures of the immature skeleton makes sonography a
      valuable tool in the management of congenital dislocation of the patella.
      Conventional radiography is a simple method for diagnosis once ossification of
      the patella has commenced and for postoperative follow-up. MRI allows
      visualization of fine anatomic details and relationships between the involved
      structures of the extensor mechanism and is the technique of choice for
      preoperative planning.

PMID- 15855132
TI  - Percutaneous cholecystostomy catheter removal and incidence of clinically
      significant bile leaks: a clinical approach to catheter management.
AB  - OBJECTIVE: We sought to determine the incidence of bile leaks upon removal of
      small-bore percutaneous cholecystostomy catheters and to evaluate clinical and
      imaging guidelines to ensure safe catheter removal. MATERIALS AND METHODS: A
      retrospective evaluation of all gallbladder drainages performed over a 5-year
      period revealed 163 patients (range, 7-98 years) who underwent percutaneous
      cholecystostomy catheter placement. Medical records and imaging studies were
      reviewed to assess the events at catheter removal (e.g., inadvertent removal,
      controlled removal with cholangiography without tract imaging, or controlled
      removal with cholangiography with tract imaging) and the incidence of major and
      minor bile leaks. RESULTS: The events at catheter removal were assessed in 66
      patients. Group 1 was 45 patients whose catheters were removed after a minimum of
      approximately 3 weeks with a cholangiogram that established cystic and common
      duct patency and no imaging of the tract. Catheters were not removed until the
      patient recovered from acute illnesses that contributed to acalculous
      cholecystitis. Group 2 was 11 patients managed similarly to group 1 except that
      tract imaging was performed at catheter removal. Group 3 was 10 patients whose
      tubes came out inadvertently without cholangiogram or tract imaging. Two major
      (group 2 and group 3) and two minor (group 2) bile leaks occurred. No bile leaks
      occurred in group 1 (p = 0.006). CONCLUSION: Major bile leaks occurred in 3% of
      patients, and minor leaks occurred with equal frequency. Tract imaging may not be
      necessary in patients with small-bore gallbladder catheters who have recovered
      from critical illness, show patent cystic and common ducts, and have had
      catheters for 3-6 weeks.

PMID- 15855133
TI  - Sonographically guided biopsy of focal lesions: a comparison of freehand and
      probe-guided techniques using a phantom.
AB  - OBJECTIVE: A phantom model of lesions in the human liver with simulated ribs was
      used to test an ultrasound probe-guided sonographic biopsy technique. The aim of
      the experiment was to compare biopsy time and sample quality between freehand and
      probe-guided methods of sonographic biopsy. MATERIALS AND METHODS: Ten operators
      with a range of clinical biopsy experience were tested. Each operator was given
      two phantoms containing four targets. Each target was biopsied with both biopsy
      methods. Data collected included procedure time and sample quality in the biopsy
      specimen. Analyses were stratified by level of operator experience. RESULTS:
      Median biopsy time was 23 sec with the ultrasound probe guide and 32 sec
      freehand. Differences between probe-guided and freehand pairs of measurements
      approximately followed a normal distribution. The mean time difference between
      probe-guided and freehand times to complete biopsy was -20 sec (95% confidence
      interval, -35 to -5 sec; p = 0.01). Analysis of sample quality across all
      operators showed no difference. CONCLUSION: The ultrasound probe-guided technique
      of sonographic biopsy could be used in a complex phantom model, and there was a
      statistically significant time benefit with the use of probe guides compared with
      the freehand biopsy technique. This benefit was greatest for inexperienced
      operators. There was no difference in sample quality between the probe-guided and
      freehand techniques.

PMID- 15855134
TI  - Sonography-guided percutaneous microwave ablation of high-grade dysplastic
      nodules in cirrhotic liver.
AB  - OBJECTIVE: Our objective was to evaluate the effect of sonography-guided
      percutaneous microwave ablation of high-grade dysplastic nodules in the cirrhotic
      liver. MATERIALS AND METHODS: From July 1997 to May 2003, 49 histologically
      proven high-grade dysplastic nodules in 30 patients with liver cirrhosis were
      treated by microwave ablation. Three patients had concomitant small
      hepatocellular carcinomas (D < 3.0 cm), whereas another three had undergone liver
      segmentectomy for hepatocellular carcinoma 1 year earlier. The mean size of the
      nodules was 1.8 cm (range, 0.9-4.6 cm). Sixty-eight insertions with 78
      applications were administered to the 49 nodules. RESULTS: The follow-up period
      was 12-82 months (mean, 45.1 +/- 19.0 months). Five patients died during this
      study: three from advanced hepatocellular carcinoma, one from bleeding in the
      upper gastrointestinal tract, and another from cerebral hemorrhage. All nodules
      showed decreased density on unenhanced CT and no enhancement on contrast-enhanced
      CT after microwave ablation. Posttreatment biopsy performed in 16 patients with
      18 nodules 1-3 months after microwave ablation showed no evidence of viable
      tissue but replacement by fibrotic tissue in all nodules. CONCLUSION:
      Percutaneous microwave ablation as a minimally invasive therapy is effective for
      ablating high-grade dysplastic nodules, thus preventing their potential malignant
      transformation, which may improve survival. The preliminary data warrant further
      prospective, randomized studies.

PMID- 15855135
TI  - Hemorrhagic complications after nephron-sparing surgery: angiographic diagnosis
      and management by transcatheter embolization.
AB  - OBJECTIVE: Nephron-sparing surgery has become an accepted treatment technique for
      renal cell carcinoma in properly selected patients. Although rare, major
      postoperative hemorrhage can occur and is usually accompanied by gross hematuria
      with or without acute flank pain at the site of prior surgery. In this
      retrospective study, the immediate radiologic and clinical success and the long
      term follow-up of transcatheter embolization are evaluated. CONCLUSION:
      Transcatheter selective embolization is a safe and effective technique for
      appropriate management of this postoperative vascular complication.

PMID- 15855136
TI  - Human thrombin for treatment of pseudoaneurysms: comparison of bovine and human
      thrombin sonogram-guided injection.
AB  - OBJECTIVE: The purpose of this research was to review our experience and
      determine the success rate of percutaneous sonogram-guided human thrombin
      injection to treat iatrogenic femoral pseudoaneurysms and compare this with the
      results obtained with bovine thrombin injection. CONCLUSION: In our experience,
      the use of human thrombin for the treatment of iatrogenic femoral pseudoaneurysms
      is highly efficient (100%), the administered dose is significantly less than with
      bovine thrombin, and the risk for allergy is potentially lower. At our hospital,
      human thrombin has replaced bovine thrombin and is the first line of treatment
      for an iatrogenic pseudoaneurysm.

PMID- 15855137
TI  - Association of internal carotid artery injury with carotid canal fractures in
      patients with head trauma.
AB  - OBJECTIVE: The purpose of our study was to determine the degree to which carotid
      canal fracture and other CT findings are associated with internal carotid artery
      (ICA) injury in patients with head trauma. MATERIALS AND METHODS: Three
      neuroradiologists retrospectively evaluated CT scans and cerebral angiograms of
      43 patients who underwent cerebral angiography within 7 days after blunt cranial
      trauma over a 5-year period. Seventeen patients underwent unilateral and 26 had
      bilateral carotid angiography. Angiograms were evaluated for ICA injury and CT
      scans were evaluated for carotid canal fracture, brain contusion, subarachnoid
      hemorrhage, basilar skull fracture, subdural hematoma, soft-tissue swelling,
      sphenoid sinus air-fluid level, and other skull fracture. We recorded the number
      of true-positive (+CT, +angiogram), true-negative (-CT, -angiogram), false
      positive (+CT, -angiogram), and false-negative (-CT, +angiogram) studies. We
      determined the sensitivity, specificity, positive predictive value, and negative
      predictive value for each CT finding. RESULTS: We identified 21 carotid canal
      fractures in 17 patients. Eleven ICA injuries were seen in 10 patients. Six
      patients with ICA injury had a carotid canal fracture. The presence of a carotid
      canal fracture had a sensitivity of 60% and specificity of 67% for detection of
      injury to the ICA passing through that canal. These values were similar to those
      for other CT findings. CONCLUSION: Sensitivity, specificity, positive predictive
      value, and negative predictive value of carotid canal fracture were only
      moderately good for determining the presence of ICA injury and were similar to
      other CT findings not typically associated with ICA injury.

PMID- 15855138
TI  - CT and MRI findings of intracranial lymphoma.

PMID- 15855139
TI  - Vertebral and spinal cord sarcoidosis.

PMID- 15855140
TI  - MRI of Susac's syndrome.

PMID- 15855141
TI  - Sonographic evaluation of cervical lymph nodes.
AB  - OBJECTIVE: Sonography is a useful imaging tool in the evaluation of cervical
      lymph nodes. Gray-scale sonography and color and power Doppler sonography are
      commonly used in clinical practice. This article documents the common sonographic
      appearances of different causes of cervical lymphadenopathy. CONCLUSION: The
      sonographic appearances of normal nodes differ from those of abnormal nodes.
      Sonographic features that help to identify abnormal nodes include shape (round),
      absent hilus, intranodal necrosis, reticulation, calcification, matting, soft
      tissue edema, and peripheral vascularity.

PMID- 15855142
TI  - How to simplify the CT diagnosis of Le Fort fractures.
AB  - OBJECTIVE: The numerous components seen in the Le Fort fractures make
      classification difficult. Our objective is to simplify the task of classifying Le
      Fort fractures. CONCLUSION: Each of the Le Fort fractures has at least one unique
      component that is easily recognizable: I, the anterolateral margin of the nasal
      fossa; II, the inferior orbital rim; and III, the zygomatic arch. Classification
      of the Le Fort fractures is simplified by using these unique components to
      establish a tentative classification that is then confirmed.

PMID- 15855143
TI  - CT dose reduction in pediatric patients.

PMID- 15855144
TI  - CT in the diagnosis of pulmonary embolism.

PMID- 15855145
TI  - Shoulder MR arthrography: which patient group benefits most?

PMID- 15855146
TI  - Quadriceps fat pad signal intensity and enlargement on MRI.

PMID- 15855147
TI  - Utilization patterns for CT pulmonary angiography.

PMID- 15855151
TI  - On the AJR viewbox. Diffuse neurofibroma of the arm: MR characteristics.

PMID- 15855152
TI  - On the AJR viewbox. Intrapancreatic accessory spleen: diagnosis with RES-specific
      contrast-enhanced MRI.

PMID- 15855153
TI  - Identification and characterization of a novel, psoriasis susceptibility-related
      noncoding RNA gene, PRINS.
AB  - To identify genetic factors contributing to psoriasis susceptibility, gene
      expression profiles of uninvolved epidermis from psoriatic patients and epidermis
      from healthy individuals were compared. Besides already characterized genes, we
      identified a cDNA with yet unknown functions, which we further characterized and
      named PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress). In
      silico structural and homology studies suggested that PRINS may function as a
      noncoding RNA. PRINS harbors two Alu elements, it is transcribed by RNA
      polymerase II, and it is expressed at different levels in various human tissues.
      Real time reverse transcription-PCR analysis showed that PRINS was expressed
      higher in the uninvolved epidermis of psoriatic patients compared with both
      psoriatic lesional and healthy epidermis, suggesting a role for PRINS in
      psoriasis susceptibility. PRINS is regulated by the proliferation and
      differentiation state of keratinocytes. Treatment with T-lymphokines, known to
      precipitate psoriatic symptoms, decreased PRINS expression in the uninvolved
      psoriatic but not in healthy epidermis. Real time reverse transcription-PCR
      analysis showed that stress signals such as ultraviolet-B irradiation, viral
      infection (herpes simplex virus), and translational inhibition increased the RNA
      level of PRINS. Gene-specific silencing of PRINS by RNA interference revealed
      that down-regulation of PRINS impairs cell viability after serum starvation but
      not under normal serum conditions. Our findings suggest that PRINS functions as a
      noncoding regulatory RNA, playing a protective role in cells exposed to stress.
      Furthermore, elevated PRINS expression in the epidermis may contribute to
      psoriasis susceptibility.

PMID- 15855154
TI  - Dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin
      (DC-SIGN)-mediated enhancement of dengue virus infection is independent of DC
      SIGN internalization signals.
AB  - Dengue virus (DV) is a mosquito-borne flavivirus that causes hemorrhagic fever in
      humans. In the natural infection, DV is introduced into human skin by an infected
      mosquito vector where it is believed to target immature dendritic cells (DCs) and
      Langerhans cells (LCs). We found that DV productively infects DCs but not LCs. We
      show here that the interactions between DV E protein, the sole mannosylated
      glycoprotein present on DV particles, and the C-type lectin dendritic cell
      specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) are
      essential for DV infection of DCs. Binding of mannosylated N-glycans on DV E
      protein to DC-SIGN triggers a rapid and efficient internalization of the viral
      glycoprotein. However, we observed that endocytosis-defective DC-SIGN molecules
      allow efficient DV replication, indicating that DC-SIGN endocytosis is
      dispensable for the internalization step in DV entry. Together, these results
      argue in favor of a mechanism by which DC-SIGN enhances DV entry and infection in
      cis. We propose that DC-SIGN concentrates mosquito-derived DV particles at the
      cell surface to allow efficient interaction with an as yet unidentified entry
      factor that is ultimately responsible for DV internalization and pH-dependent
      fusion into DCs.

PMID- 15855155
TI  - AGP2 encodes the major permease for high affinity polyamine import in
      Saccharomyces cerevisiae.
AB  - Polyamines play essential functions in many aspects of cell biology. Plasma
      membrane transport systems for the specific uptake of polyamines exist in most
      eukaryotic cells but have been very recently identified at the molecular level
      only in the parasite Leishmania. We now report that the high affinity polyamine
      permease in Saccharomyces cerevisiae is identical to Agp2p, a member of the yeast
      amino acid transporter family that was previously identified as a carnitine
      transporter. Deletion of AGP2 dramatically reduces the initial velocity of
      spermidine and putrescine uptake and confers strong resistance to the toxicity of
      exogenous polyamines, and transformation with an AGP2 expression vector restored
      polyamine transport in agp2delta mutants. Yeast mutants deficient in polyamine
      biosynthesis required >10-fold higher concentrations of exogenous putrescine to
      restore cell proliferation upon deletion of the AGP2 gene. Disruption of END3, a
      gene required for an early step of endocytosis, increased the abundance of Agp2p,
      an effect that was paralleled by a marked up-regulation of spermidine transport
      velocity. Thus, AGP2 encodes the first eukaryotic permease that preferentially
      uses spermidine over putrescine as a high affinity substrate and plays a central
      role in the uptake of polyamines in yeast.

PMID- 15855156
TI  - Molecular conversion of NAD kinase to NADH kinase through single amino acid
      residue substitution.
AB  - NAD kinase phosphorylates NAD+ to form NADP+ and is strictly specific to NAD+,
      whereas NADH kinase phosphorylates both NAD+ and NADH, thereby showing relaxed
      substrate specificity. Based on their primary and tertiary structures, the
      difference in the substrate specificities between NAD and NADH kinases was
      proposed to be caused by one aligned residue: Gly or polar amino acid (Gln or
      Thr) in five NADH kinases and a charged amino acid (Arg) in two NAD kinases. The
      substitution of Arg with Gly in the two NAD kinases relaxed the substrate
      specificity (i.e. converted the NAD kinases to NADH kinases). The substitution of
      Arg in one NAD kinase with polar amino acids also relaxed the substrate
      specificity, whereas substitution with charged and hydrophobic amino acids did
      not show a similar result. In contrast, the substitution of Gly with Arg in one
      NADH kinase failed to convert it to NAD kinase. These results suggest that a
      charged or hydrophobic amino acid residue in the position of interest is crucial
      for strict specificity of NAD kinases to NAD+, whereas Gly or polar amino acid
      residue is not the sole determinant for the relaxed substrate specificity of NADH
      kinases. The significance of the conservation of the residue at the position in
      207 NAD kinase homologues is also discussed.

PMID- 15855157
TI  - Hyperphosphorylation of the BARD1 tumor suppressor in mitotic cells.
AB  - Although the BRCA1 tumor suppressor has been implicated in a number of cellular
      processes, it plays an especially important role in the DNA damage response as a
      regulator of cell cycle checkpoints and DNA repair pathways. In vivo, BRCA1
      exists as a heterodimer with the BARD1 protein, and many of its biological
      functions are mediated by the BRCA1-BARD1 complex. Here, we show that BARD1 is
      phosphorylated in a cell cycle-dependent manner and that the hyperphosphorylated
      forms of BARD1 predominate during M phase. By mobility shift analysis and mass
      spectrometry, we have identified seven sites of mitotic phosphorylation within
      BARD1. All sites exist within either an SP or TP sequence, and two sites resemble
      the consensus motif recognized by cyclin-dependent kinases. To examine the
      functional consequences of BARD1 phosphorylation, we used a gene targeting knock
      in approach to generate isogenic cell lines that express either wild-type or
      mutant forms of the BARD1 polypeptide. Analysis of these lines in clonogenic
      survival assays revealed that cells bearing phosphorylation site mutations are
      hypersensitive to mitomycin C, a genotoxic agent that induces interstrand DNA
      cross-links. These results implicate BARD1 phosphorylation in the cellular
      response to DNA damage.

PMID- 15855158
TI  - Combined proteome and metabolite-profiling analyses reveal surprising insights
      into yeast sulfur metabolism.
AB  - Metabolomics is considered as an emerging new tool for functional proteomics in
      the identification of new protein function or in projects aiming at modeling
      whole cell metabolism. When combined with proteome studies, metabolite-profiling
      analyses revealed unanticipated insights into the yeast sulfur pathway. In
      response to cadmium, the observed overproduction of glutathione, essential for
      the detoxification of the metal, can be entirely accounted for by a marked drop
      in sulfur-containing protein synthesis and a redirection of sulfur metabolite
      fluxes to the glutathione pathway. A kinetic analysis showed sequential and
      dramatic changes in intermediate sulfur metabolite pools within the first hours
      of the treatment. Strikingly, whereas proteome and metabolic data were positively
      correlated under cadmium conditions, proteome and metabolic data were negatively
      correlated during other growth conditions, i.e. methionine supplementation or
      sulfate starvation. These differences can be explained by alternative mechanisms
      in the regulation of Met4, the activator of the sulfur pathway. Whereas Met4
      activity is controlled by the cellular cysteine content in response to sulfur
      source and availability, the present study suggests that Met4 activation under
      cadmium conditions is cysteine-independent. The results clearly indicate that the
      metabolic state of a cell cannot be safely predicted based solely on proteomic
      and/or gene expression data. Combined metabolome and proteome studies are
      necessary to draw a comprehensive and integrated view of cell metabolism.

PMID- 15855159
TI  - Immediate early gene X1 (IEX-1) is organized in subnuclear structures and
      partially co-localizes with promyelocytic leukemia protein in HeLa cells.
AB  - Immediate early gene X1 (IEX-1) represents a stress response gene involved in
      growth control and modulation of apoptosis. Here, we report a detailed analysis
      of IEX-1 with respect to its intracellular localization. By means of confocal
      laser scanning microscopy, a green fluorescent protein-IEX-1 fusion protein
      transfected into HeLa cells, as well as endogenous IEX-1, could be detected in
      distinct subnuclear structures. This particular subnuclear localization of IEX-1
      was not observed with a green fluorescent protein-IEX-1 fusion protein lacking a
      putative nuclear localization sequence, along with a decreased effect on
      apoptosis. Double immunofluorescence staining revealed a partial co-localization
      of endogenous promyelocytic leukemia protein (PML) and IEX-1 in these subnuclear
      structures. Nuclear localization of IEX-1 is also enhanced upon treatment of
      cells with leptomycin B, an inhibitor of the nuclear exporter CRM1. These
      observations indicate that IEX-1 is specifically shuttled to and from the
      nucleus. Overexpression experiments using PML isoforms III and IV revealed
      distinct intranuclear interaction of IEX-1 and PML. Coprecipitation experiments
      showed physical interaction between IEX-1 and PML. The close structural relation
      of IEX-1-containing nuclear subdomains and PML nuclear bodies suggests a function
      of IEX-1 related to the multiple functions of these unique subnuclear regions,
      particularly during stress response and growth control.

PMID- 15855160
TI  - Sites of tau important for aggregation populate {beta}-structure and bind to
      microtubules and polyanions.
AB  - The aggregation of the microtubule-associated tau protein and formation of
      "neurofibrillary tangles" is one of the hallmarks of Alzheimer disease. The
      mechanisms underlying the structural transition of innocuous, natively unfolded
      tau to neurotoxic forms and the detailed mechanisms of binding to microtubules
      are largely unknown. Here we report the high-resolution characterization of the
      repeat domain of soluble tau using multidimensional NMR spectroscopy. NMR
      secondary chemical shifts detect residual beta-structure for 8-10 residues at the
      beginning of repeats R2-R4. These regions correspond to sequence motifs known to
      form the core of the cross-beta-structure of tau-paired helical filaments.
      Chemical shift perturbation studies show that polyanions, which promote paired
      helical filament aggregation, as well as microtubules interact with tau through
      positive charges near the ends of the repeats and through the beta-forming motifs
      at the beginning of repeats 2 and 3. The high degree of similarity between the
      binding of polyanions and microtubules supports the hypothesis that stable
      microtubules prevent paired helical filament formation by blocking the tau
      polyanion interaction sites, which are crucial for paired helical filament
      formation.

PMID- 15855161
TI  - Delineation of positron emission tomography imaging agent binding sites on beta
      amyloid peptide fibrils.
AB  - A range of imaging agents for use in the positron emission tomography of
      Alzheimer's disease is currently under development. Each of the main compound
      classes, derived from thioflavin T (PIB), Congo Red (BSB), and aminonaphthalene
      (FDDNP) are believed to bind to mutually exclusive sites on the beta-amyloid
      (Abeta) peptide fibrils. We recently reported the presence of three classes of
      binding sites (BS1, BS2, BS3) on the Abeta fibrils for thioflavin T derivatives
      and now extend these findings to demonstrate that these sites are also able to
      accommodate ligands from the other chemotype classes. The results from
      competition assays using [3H]Me-BTA-1 (BS3 probe) indicated that both PIB and
      FDDNP were able to displace the radioligand with Ki values of 25 and 42 nM,
      respectively. BSB was unable to displace the radioligand tracer from the Abeta
      fibrils. In contrast, each of the compounds examined were able to displace
      thioflavin T (BS1 probe) from the Abeta fibrils when evaluated in a fluorescence
      competition assay with Ki values for PIB, FDDNP, and BSB of 1865, 335, and 600
      nM, respectively. Finally, the Kd values for FDDNP and BSB binding to Abeta
      fibrils were directly determined by monitoring the increases in the ligand
      intrinsic fluorescence, which were 290 and 104 nM, respectively. The results from
      these assays indicate that (i) the three classes of thioflavin T binding sites
      are able to accommodate a wide range of chemotype structures, (ii) BSB binds to
      two sites on the Abeta fibrils, one of which is BS2, and the other is distinct
      from the thioflavin T derivative binding sites, and (iii) there is no independent
      binding site on the fibrils for FDDNP, and the ligand binds to both the BS1 and
      BS3 sites with significantly lower affinities than previously reported.

PMID- 15855162
TI  - A three-component dicamba O-demethylase from Pseudomonas maltophilia, strain DI
      6: gene isolation, characterization, and heterologous expression.
AB  - Dicamba O-demethylase is a multicomponent enzyme from Pseudomonas maltophilia,
      strain DI-6, that catalyzes the conversion of the widely used herbicide dicamba
      (2-methoxy-3,6-dichlorobenzoic acid) to DCSA (3,6-dichlorosalicylic acid). We
      recently described the biochemical characteristics of the three components of
      this enzyme (i.e. reductase(DIC), ferredoxin(DIC), and oxygenase(DIC)) and
      classified the oxygenase component of dicamba O-demethylase as a member of the
      Rieske non-heme iron family of oxygenases. In the current study, we used N
      terminal and internal amino acid sequence information from the purified proteins
      to clone the genes that encode dicamba O-demethylase. Two reductase genes (ddmA1
      and ddmA2) with predicted amino acid sequences of 408 and 409 residues were
      identified. The open reading frames encode 43.7- and 43.9-kDa proteins that are
      99.3% identical to each other and homologous to members of the FAD-dependent
      pyridine nucleotide reductase family. The ferredoxin coding sequence (ddmB)
      specifies an 11.4-kDa protein composed of 105 residues with similarity to the
      adrenodoxin family of [2Fe-2S] bacterial ferredoxins. The oxygenase gene (ddmC)
      encodes a 37.3-kDa protein composed of 339 amino acids that is homologous to
      members of the Phthalate family of Rieske non-heme iron oxygenases that function
      as monooxygenases. Southern analysis localized the oxygenase gene to a
      megaplasmid in cells of P. maltophilia. Mixtures of the three highly purified
      recombinant dicamba O-demethylase components overexpressed in Escherichia coli
      converted dicamba to DCSA with an efficiency similar to that of the native
      enzyme, suggesting that all of the components required for optimal enzymatic
      activity have been identified. Computer modeling suggests that oxygenase(DIC) has
      strong similarities with the core alphasubunits of naphthalene 1,2-dioxygenase.
      Nonetheless, the present studies point to dicamba O-demethylase as an enzyme
      system with its own unique combination of characteristics.

PMID- 15855163
TI  - Cyclooxygenase-2-derived prostaglandin E2 promotes human cholangiocarcinoma cell
      growth and invasion through EP1 receptor-mediated activation of the epidermal
      growth factor receptor and Akt.
AB  - Cyclooxygenase-2 (COX-2)-mediated prostaglandin synthesis has recently been
      implicated in human cholangiocarcinogenesis. This study was designed to examine
      the mechanisms by which COX-2-derived prostaglandin E2 (PGE2) regulates
      cholangiocarcinoma cell growth and invasion. Immunohistochemical analysis
      revealed elevated expression of COX-2 and the epidermal growth factor (EGF)
      receptor (EGFR) in human cholangiocarcinoma tissues. Overexpression of COX-2 in a
      human cholangiocarcinoma cell line (CCLP1) increased tumor cell growth and
      invasion in vitro and in severe combined immunodeficient mice. Overexpression of
      COX-2 or treatment with PGE2 or the EP1 receptor agonist ONO-DI-004 induced
      phosphorylation of EGFR and enhanced tumor cell proliferation and invasion, which
      were inhibited by the EP1 receptor small interfering RNA or antagonist ONO-8711.
      Treatment of CCLP1 cells with PGE2 or ONO-DI-004 enhanced binding of EGFR to the
      EP1 receptor and c-Src. Furthermore, PGE2 or ONO-DI-004 treatment also increased
      Akt phosphorylation, which was blocked by the EGFR tyrosine kinase inhibitors AG
      1478 and PD 153035. These findings reveal that the EP1 receptor transactivated
      EGFR, thus activating Akt. On the other hand, activation of EGFR by its cognate
      ligand (EGF) increased COX-2 expression and PGE2 production, whereas blocking
      PGE2 synthesis or the EP1 receptor inhibited EGF-induced EGFR phosphorylation.
      This study reveals a novel cross-talk between the EP1 receptor and EGFR signaling
      that synergistically promotes cancer cell growth and invasion.

PMID- 15855164
TI  - Mitochondrial Dok-4 recruits Src kinase and regulates NF-kappaB activation in
      endothelial cells.
AB  - The downstream of kinase (Dok) family of adapter proteins consists of at least
      five members structurally characterized by an NH2-terminal tandem of conserved
      pleckstrin homology and phosphotyrosine binding domains linked to a unique COOH
      terminal region. To determine the role of the novel adapter protein Dok-4 in
      endothelial cells, we first investigated the cell localization of Dok-4. Most
      surprisingly, immunofluorescence microscopy, cell fractionation studies, and
      studies with enhanced green fluorescent protein chimeras showed that wild type
      Dok-4 (Dok-4-WT) specifically localized in mitochondria. An NH2-terminal deletion
      mutant of Dok-4 (Dok-4-(deltaN11-29)), which lacks the mitochondrial targeting
      sequence, could not accumulate in mitochondria. Co-immunoprecipitation revealed
      an interaction of c-Src with Dok-4-WT in endothelial cells. Most interestingly,
      overexpression of Dok-4-WT, but not Dok-4-(deltaN1-99), increased mitochondrial c
      Src expression, whereas knock-down of endogenous Dok-4 with a small interfering
      RNA vector greatly inhibited mitochondrial localization of c-Src, suggesting a
      unique function for Dok-4 as an anchoring protein for c-Src in mitochondria. Dok
      4-WT significantly decreased 39-kDa subunit complex I expression. PP2, a specific
      Src kinase inhibitor, prevented the Dok-4-mediated complex I decrease, suggesting
      the involvement of Src kinase in regulation of complex I expression. Dok-4-WT
      enhanced tumor necrosis factor-alpha (TNF-alpha)-mediated reactive oxygen species
      (ROS) production, supporting the functional relevance of a Dok-4-Src-complex
      I/ROS signaling pathway in mitochondria. Finally, Dok-4 enhanced TNF-alpha
      mediated NF-kappaB activation, whereas this was inhibited by transfection with
      Dok-4 small interfering RNA. In addition, Dok-4-induced NF-kappaB activation was
      also inhibited by transfection of a dominant negative form of c-Src. These data
      suggest a role for mitochondrial Dok-4 as an anchoring molecule for the tyrosine
      kinase c-Src, and in turn as a regulator of TNF-alpha-mediated ROS production and
      NF-kappaB activation.

PMID- 15855165
TI  - Prostaglandin signaling in the renal collecting duct: release, reuptake, and
      oxidation in the same cell.
AB  - Prostaglandins mediate autacrine and paracrine signaling over short distances. We
      used the renal collecting duct as a model system to test the hypothesis that
      local control of prostaglandin signaling is achieved by expressing inactivation
      in the same cell as synthesis. Immunocytochemical studies demonstrated that renal
      collecting ducts in situ express the prostaglandin (PG) synthesis enzyme,
      cyclooxygenase-1 (COX-1), as well as both components of prostaglandin metabolic
      inactivation, i.e. the prostaglandin uptake carrier prostaglandin transporter
      (PGT) and the enzyme 15-hydroxyprostaglandin dehydrogenase. We characterized this
      system further using the collecting duct cell line Madin-Darby canine kidney
      (MDCK), which retains COX-2 and prostaglandin dehydrogenase expression but which
      has lost PGT expression. When we reintroduced PGT, it was correctly sorted to the
      apical membrane where it altered the sidedness of prostaglandin E2 (PGE2)
      release, a process we call "vectorial release via sided reuptake." Importantly,
      although COX-2 and prostaglandin dehydrogenase are expressed in the same MDCK
      cell, they must be compartmentalized because even in the presence of excess
      dehydrogenase newly synthesized PGE2 is released largely un-oxidized. However,
      when PGE2 undergoes first release and then PGT-mediated reuptake, significant
      oxidation takes place, suggesting that PGT imports PGE2 into the prostaglandin
      dehydrogenase compartment. Our data are consistent with a new model that offers
      significant new mechanisms for the fine control of eicosanoid signaling.

PMID- 15855166
TI  - Identification of a cyclin T-binding domain in Hexim1 and biochemical analysis of
      its binding competition with HIV-1 Tat.
AB  - The active form of the positive transcription elongation factor b (P-TEFb)
      consists of cyclin T and the kinase Cdk9. P-TEFb stimulates transcription by
      phosphorylating the C-terminal domain of RNA polymerase II. It becomes
      inactivated when associated in a tetrameric complex with the abundant 7SK small
      nuclear RNA and the recently identified protein Hexim1. In this study, we
      identified a stable and soluble C-terminal domain (residues 255-359) in Hexim1 of
      12.5-kDa size that binds the cyclin boxes of Cyclin T1. Functional assays in HeLa
      cells showed that this cyclin T-binding domain (TBD) is required for the binding
      of Hexim1 to P-TEFb and inhibition of transcriptional activity in vivo.
      Analytical gel filtration and GST pull-down experiments revealed that both full
      length Hexim1 and the TBD are homodimers. Isothermal titration calorimetry
      yielded a weak multimer for the TBD with a multimerization constant of 1.3 x
      10(3) m. The binding affinity between the TBD and cyclin T1 was analyzed with
      fluorescence spectroscopy methods, using a dansyl-based fluorescence label at
      position G257C. Equilibrium fluorescence titration and stopped flow fast kinetics
      yield a dissociation constant of 1.2 mum. Finally, we tested the effect of the
      HIV-1 Tat protein on the cyclin T1-TBD complex formation. GST pull-down
      experiments and size exclusion chromatography exhibit a mutually exclusive
      binding of the two effectors to cyclin T1. Our data suggest a model where HIV-1
      Tat competes with Hexim1 for cyclin T1 binding, thus releasing P-TEFb from the
      inactive complex to stimulate the transcription of HIV-1 gene expression.

PMID- 15855167
TI  - Integrase mutants defective for interaction with LEDGF/p75 are impaired in
      chromosome tethering and HIV-1 replication.
AB  - The insertion of a DNA copy of its RNA genome into a chromosome of the host cell
      is mediated by the viral integrase with the help of mostly uncharacterized
      cellular cofactors. We have recently described that the transcriptional co
      activator LEDGF/p75 strongly interacts with HIV-1 integrase. Here we show that
      interaction of HIV-1 integrase with LEDGF/p75 is important for viral replication.
      Using multiple approaches including two-hybrid interaction studies, random and
      directed mutagenesis, we could demonstrate that HIV-1 virus harboring a single
      mutation that disrupts integrase-LEDGF/p75 interaction, resulted in defective HIV
      1 replication. Furthermore, we found that LEDGF/p75 tethers HIV-1 integrase to
      chromosomes and that this interaction may be important for the integration
      process and the replication of HIV-1.

PMID- 15855168
TI  - Degradation of Cdt1 during S phase is Skp2-independent and is required for
      efficient progression of mammalian cells through S phase.
AB  - Previous reports have shown that the N terminus of Cdt1 is required for its
      degradation during S phase (Li, X., Zhao, Q., Liao, R., Sun, P., and Wu, X.
      (2003) J. Biol. Chem. 278, 30854-30858; Nishitani, H., Lygerou, Z., and
      Nishimoto, T. (2004) J. Biol. Chem. 279, 30807-30816). The stabilization was
      attributed to deletion of the cyclin binding motif (Cy motif), which is required
      for its phosphorylation by cyclin-dependent kinases. Phosphorylated Cdt1 is
      subsequently recognized by the F-box protein Skp2 and targeted for proteasomal
      mediated degradation. Using phosphopeptide mapping and mutagenesis studies, we
      found that threonine 29 within the N terminus of Cdt1 is phosphorylated by Cdk2
      and required for interaction with Skp2. However, threonine 29 and the Cy motif
      are not necessary for proteolysis of Cdt1 during S phase. Mutants of Cdt1 that do
      not stably associate with Skp2 or cyclins are still degraded in S phase to the
      same extent as wild type Cdt1, indicating that other determinants within the N
      terminus of Cdt1 are required for degrading Cdt1. We localized the region
      necessary for Cdt1 degradation to the first 32 residues. Overexpression of stable
      forms of Cdt1 significantly delayed entry into and completion of S phase,
      suggesting that failure to degrade Cdt1 prevents normal progression through S
      phase. In contrast, Cdt1 mutants that fail to interact with Skp2 and cyclins
      progress through S phase with similar kinetics as wild type Cdt1 but stimulate
      the re-replication caused by overexpressing Cdt1. Therefore, a Skp2-independent
      pathway that requires the N-terminal 32 residues of Cdt1 is critical for the
      degradation of Cdt1 in S phase, and this degradation is necessary for the optimum
      progression of cells through S phase.

PMID- 15855169
TI  - Reactive carbonyls and polyunsaturated fatty acids produce a hydroxyl radical
      like species: a potential pathway for oxidative damage of retinal proteins in
      diabetes.
AB  - The pattern of oxidized amino acids in aortic proteins of nonhuman primates
      suggests that a species resembling hydroxyl radical damages proteins when blood
      glucose levels are high. However, recent studies argue strongly against a
      generalized increase in diabetic oxidative stress, which might instead be
      confined to the vascular wall. Here, we describe a pathway for glucose-stimulated
      protein oxidation and provide evidence of its complicity in diabetic
      microvascular disease. Low density lipoprotein incubated with pathophysiological
      concentrations of glucose became selectively enriched in ortho-tyrosine and meta
      tyrosine, implicating a hydroxyl radical-like species in protein damage. Model
      system studies demonstrated that the reaction pathway requires both a reactive
      carbonyl group and a polyunsaturated fatty acid, involves lipid peroxidation, and
      is blocked by the carbonyl scavenger aminoguanidine. To explore the physiological
      relevance of the pathway, we used mass spectrometry and high pressure liquid
      chromatography to quantify oxidation products in control and hyperglycemic rats.
      Hyperglycemia raised levels of ortho-tyrosine, meta-tyrosine, and oxygenated
      lipids in the retina, a tissue rich in polyunsaturated fatty acids. Rats that
      received aminoguanidine did not show this increase in protein and lipid
      oxidation. In contrast, rats with diet-induced hyperlipidemia in the absence of
      hyperglycemia failed to exhibit increased protein and lipid oxidation products in
      the retina. Our observations suggest that generation of a hydroxyl radical-like
      species by a carbonyl/polyunsaturated fatty acid pathway might promote localized
      oxidative stress in tissues vulnerable to diabetic damage. This raises the
      possibility that antioxidant therapies that specifically inhibit the pathway
      might delay the vascular complications of diabetes.

PMID- 15855170
TI  - Hmi1p from Saccharomyces cerevisiae mitochondria is a structure-specific DNA
      helicase.
AB  - Hmi1p is a Saccharomyces cerevisiae mitochondrial DNA helicase that is essential
      for the maintenance of functional mitochondrial DNA. Hmi1p belongs to the
      superfamily 1 of helicases and is a close homologue of bacterial PcrA and Rep
      helicases. We have overexpressed and purified recombinant Hmi1p from Escherichia
      coli and describe here the biochemical characteristics of its DNA helicase
      activities. Among nucleotide cofactors, the DNA unwinding by Hmi1p was found to
      occur efficiently only in the presence of ATP and dATP. Hmi1p could unwind only
      the DNA substrates with a 3'-single-stranded overhang. The length of the 3'
      overhang needed for efficient targeting of the helicase to the substrate depended
      on the substrate structure. For substrates consisting of duplex DNA with a 3'
      single-stranded DNA overhang, at least a 19-nt 3'-overhang was needed. In the
      case of forked substrates with both 3'- and 5'-overhangs, a 9-nt 3'-overhang was
      sufficient provided that the 5'-overhang was also 9 nt in length. In flap
      structured substrates mimicking the chain displacement structures in DNA
      recombination process, only a 5-nt 3'-single-stranded DNA tail was required for
      efficient unwinding by Hmi1p. These data indicate that Hmi1p may be targeted to a
      specific 3'-flap structure, suggesting its possible role in DNA recombination.

PMID- 15855171
TI  - Direct interaction of the N-terminal domain of focal adhesion kinase with the N
      terminal transactivation domain of p53.
AB  - Focal adhesion kinase (FAK) is a nonreceptor kinase that is overexpressed in many
      types of tumors and associates with multiple cell surface receptors and
      intracellular signaling proteins through which it can play an important role in
      survival signaling. A link between FAK and p53 in survival signaling has been
      reported, although the molecular basis of these events has not been described. In
      the present study, we report that FAK physically and specifically interacts with
      p53 as demonstrated by pull-down, immunoprecipitation, and co-localization
      analyses. Using different constructs of N-terminal, central, and C-terminal
      fragments of FAK and p53 proteins, we determined that the N-terminal fragment of
      FAK directly interacts with the N-terminal transactivation domain of p53.
      Inhibition of p53 with small interfering p53 RNA resulted in a decreased complex
      of FAK and p53 proteins in 293 cells, and induction of p53 with doxorubicin in
      normal human fibroblasts caused an increase of FAK and p53 interaction.
      Introduction of the FAK plasmid into p53-null SAOS-2 cells was able to rescue
      these cells from apoptosis induced by expression of wild type p53. In HCT 116
      colon cancer cells, co-transfection of FAK plasmid with p21, MDM-2, and BAX
      luciferase plasmids resulted in significant inhibition of p53-responsive
      luciferase activities, demonstrating that FAK can reduce transcriptional activity
      of p53. The results of the FAK and p53 interaction study strongly support the
      conclusion that FAK can suppress p53-mediated apoptosis and inhibit
      transcriptional activity of p53. This provides a novel mechanism for FAK-p53
      mediated survival/apoptotic signaling.

PMID- 15855172
TI  - Neuronal differentiation of bone marrow-derived stromal stem cells involves
      suppression of discordant phenotypes through gene silencing.
AB  - Tissue engineering involves the construction of transplantable tissues in which
      bone marrow aspirates may serve as an accessible source of autogenous
      multipotential mesenchymal stem cells. Increasing reports indicate that the
      lineage restriction of adult mesenchymal stem cells may be less established than
      previously believed, and stem cell-based therapeutics await the establishment of
      an efficient protocol capable of achieving a prescribed phenotype
      differentiation. We have investigated how adult mouse bone marrow-derived stromal
      cells (BMSCs) are guided to neurogenic and osteogenic phenotypes. Naive BMSCs
      were found surprisingly active in expression of a wide range of mRNAs and
      proteins, including those normally reported in terminally differentiated neuronal
      cells and osteoblasts. The naive BMSCs were found to exhibit voltage-dependent
      membrane currents similar to the neuronally guided BMSCs, although with smaller
      amplitudes. Once BMSCs were exposed to the osteogenic culture condition, the
      neuronal characteristics quickly disappeared. Our data suggest that the loss of
      discordant phenotypes during BMSC differentiation cannot be explained by the
      selection and elimination of unfit cells from the whole BMSC population. The
      percent ratio of live to dead BMSCs examined did not change during the first 8-10
      days in either neurogenic or osteogenic differentiation media, and cell
      detachment was estimated at <1%. However, during this period, bone-associated
      extracellular matrix genes were selectively down-regulated in neuronally guided
      BMSCs. These data indicate that the suppression of discordant phenotypes of
      differentiating adult stem cells is achieved, at least in part, by silencing of
      superfluous gene clusters.

PMID- 15855173
TI  - Identification of placental transforming growth factor-beta and bikunin
      metabolites as contaminants of pharmaceutical human chorionic gonadotrophin
      preparations by proteomic techniques.
AB  - A contaminant protein complex found in pharmaceutical urinary human chorionic
      gonadotrophin preparations is reported to have anti-human immunodeficiency virus
      associated Kaposi's sarcoma activity. The aim of this study was to isolate and
      characterize this protein complex by proteomic approaches. Size exclusion
      chromatography was used in the isolation of these human chorionic gonadotrophin
      associated fragments. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      showed the presence of a protein complex that dissociated into two protein bands
      under reducing conditions. Matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry of this complex showed three polypeptides at
      approximately 6.2, 11.4, and 15.8 kDa. Peptide mass mapping and N-terminal amino
      acid sequencing identified two polypeptides as metabolites of placental
      transforming growth factor-beta (11.4 kDa) and bikunin (15.8 kDa). Subsequent
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometric
      analysis of the anti-human immunodeficiency virus-associated Kaposi's sarcoma
      active preparations CG-10 (Sigma), Pregnyl (Organon), and Profasi (Serono)
      revealed the presence of metabolites of placental transforming growth factor-beta
      in all three; no other non-human chorionic gonadotrophin-related protein species
      were observed in these preparations. Our findings present evidence that urinary
      human chorionic gonadotrophin preparations are contaminated with metabolites of
      placental transforming growth factor-beta, which may have transforming growth
      factor-beta agonist actions, and metabolites of bikunin, which is a protease
      inhibitor. In combination these molecules may be responsible for the anti-human
      immunodeficiency virus-associated Kaposi's sarcoma activity demonstrated for
      these urinary human chorionic gonadotrophin preparations.

PMID- 15855174
TI  - Modulation of differentiation-related gene 1 expression by cell cycle blocker
      mimosine, revealed by proteomic analysis.
AB  - L-mimosine, a plant amino acid, can reversibly block mammalian cells at late G1
      phase and has been found to affect translation of mRNAs of the cyclin-dependent
      kinase inhibitor p27, eIF3a (eIF3 p170), and ribonucleotide reductase M2. The
      effect of mimosine on the expression of these genes may be essential for the G1
      phase arrest. To determine additional genes that may be early respondents to the
      mimosine treatment, we performed two-dimensional gel electrophoretic analysis of
      [35S]methionine-labeled cell lysates followed by identification of the altered
      protein spots by LC-tandem mass spectrometry. In this study, the synthesis of two
      protein spots (MIP42 and MIP17) was found to be enhanced by mimosine, whereas the
      formation of another protein spot (MSP17) was severely blocked following mimosine
      treatment. These protein spots, MIP42, MIP17, and MSP17, were identified to be
      differentiation-related gene 1 (Drg-1; also called RTP, cap43, rit42, Ndrg-1, and
      PROXY-1), deoxyhypusine-containing eIF5A intermediate, and mature hypusine
      containing eIF5A, respectively. The effect of mimosine on eIF5A maturation was
      due to inhibition of deoxyhypusine hydroxylase, the enzyme catalyzing the final
      step of hypusine biosynthesis in eIF5A. The mimosine-induced expression of Drg-1
      was mainly attributable to increased transcription likely by the c-Jun/AP-1
      transcription factor. Because induction of Drg-1 is an early event after mimosine
      treatment and is observed before a notable reduction in the steady-state level of
      mature eIF5A, eIF5A does not appear to be involved in the modulation of Drg-1
      expression.

PMID- 15855175
TI  - Cardiotoxicity of de Gramont's regimen: incidence, clinical characteristics and
      long-term follow-up.
AB  - BACKGROUND: The incidence of 5-fluorouracil (5-FU)-related cardiotoxicity seems
      to be dosage and schedule dependent. It was reported as 1.6-3% with earlier bolus
      regimens whereas this increased up to 7.6-18% with prolonged (4-5 days) infusion
      regimens. Knowledge of the cardiotoxicity incidence in patients treated with the
      widely used de Gramont's regimen (2 days infusional 5-FU) and the long-term
      follow-up of affected patients is still limited. METHODS: We investigated the
      incidence and clinical characteristics of the cardiotoxicity of de Gramont's
      regimen and long-term follow-up of the affected patients. RESULTS: Nine of a
      total of 231 patients receiving de Gramont's regimen experienced cardiac events,
      revealing an overall incidence of 3.9%. Four (2.5%) cases were receiving de
      Gramont's regimen only. Cardiac manifestations were acute coronary syndrome (n =
      6), congestive heart failure (n = 2) and atrial fibrillation (n = 1).
      Cardiotoxicity occurred in the first cycle in eight patients, and in the second
      cycle in one. The median onset day was day 2. Cardiac symptoms occurred mostly at
      night time (seven patients) and the onset was a few hours after the bolus part of
      the regimen in four out of seven patients. After the cardiotoxicity, treatments
      were continued safely without 5-FU. CONCLUSIONS: de Gramont's regimen has a lower
      incidence of cardiotoxicity compared with more prolonged 5-FU-based infusion
      regimens. Nevertheless, patients should still be carefully monitored especially
      in the first cycles and at night time.

PMID- 15855176
TI  - A video questionnaire identifies upper airway abnormalities in preschool children
      with reported wheeze.
AB  - BACKGROUND: Accurate characterisation of subjects is essential to interpret data
      from studies investigating preschool wheezing. AIM: To assess whether a video
      questionnaire (VQ) identifies upper airway abnormalities in preschool children
      with reported wheeze. METHODS: Forty three children (median age 17 months, range
      3-58) undergoing fibreoptic bronchoscopy for clinical investigation of
      troublesome noisy breathing at a tertiary centre were studied. Parents were shown
      a VQ with four clips (wheeze, stridor, and two other upper respiratory noises)
      and chose the clip(s) resembling their child's main symptom. Doctor observed
      symptoms, parental reported symptoms, and symptoms identified on VQ were related
      to bronchoscopy. RESULTS: Thirty subjects had wheeze as the main symptom: 19 had
      doctor observed wheeze (DOW) and 11 had parental reported wheeze (RW). Parents of
      two of the subjects with RW identified wheeze alone on VQ and both had normal
      bronchoscopic findings. Five of the remaining nine subjects with RW had upper
      airway abnormalities at bronchoscopy. Parents of six subjects with RW identified
      a noise other than wheeze on VQ; four of these had upper airway abnormalities.
      Parents of two subjects with RW did not identify a noise on VQ; one had upper
      airway abnormalities. Of the 19 with DOW, nine parents identified wheeze alone on
      VQ, and all had a normal upper airway. Parents of nine subjects with DOW
      identified a noise other than wheeze as an equal or only symptom, (no noise
      identified in one), and five had upper airway abnormalities. CONCLUSION: A VQ
      helps to identify upper airway abnormalities in preschool children with a history
      of wheezing.

PMID- 15855177
TI  - Survey of psychosocial support provided by UK paediatric oncology centres.
AB  - AIM: To obtain a comprehensive overview of current patterns of psychosocial
      support provided by National Health Service (NHS) paediatric oncology treatment
      centres across the UK. METHODS: A postal questionnaire was sent to co-ordinators
      in the UK Children's Cancer Study Group (a professional body that is responsible
      for the organisation of treatment and management of childhood cancer in the UK)
      in 21 treatment centres and three separate Teenage Cancer Trus units. A range of
      psychosocial topics were explored, including ratio of staff providing support to
      patients; facilities provided for children and families; psychosocial support
      services such as support groups; information provision; and transition support.
      RESULTS: There were many good areas of support provided by centres, but there was
      also a lack of standard practices and procedures. All centres employed social
      workers, play specialists, and paediatric oncology outreach nurses, but patient
      to staff ratios varied across centres. The poorest staff provision was among
      psychologists, where patient to staff ratios ranged from 132:1 to 1100:1. Written
      information was standard practice, while provision of other types of information
      (audiovisual, online) varied; none of the centres provided audio information
      specifically for children/young people. CONCLUSION: This variability in practices
      among centres frequently occurred, as centres rarely had procedures formally
      agreed or recorded in writing. British government policy currently seeks to
      develop standards and guidelines of care throughout the National Health Service.
      This study further demonstrates the importance of standards and the need to agree
      guidelines for the provision of psychosocial support for children/young people
      and their families throughout the course of the illness.

PMID- 15855178
TI  - Respiratory illness associated with influenza and respiratory syncytial virus
      infection.
AB  - AIMS: To estimate excess morbidity during periods of influenza and respiratory
      syncytial virus (RSV) activity. METHODS: Retrospective analysis of a sentinel
      practice network database in active and non-active virus periods. MAIN OUTCOME
      MEASURES: clinical diagnoses of new episodes of influenza-like illness (ILI),
      acute bronchitis, asthma, and otitis media. RESULTS: The clinical diagnosis of
      ILI was consistent with influenza virus activity and acute bronchitis with RSV.
      During periods of virus activity, estimates of excess morbidity in children aged
      1-4 and 5-14 years diagnosed as having acute otitis media exceeded those
      diagnosed with each of the other three conditions; in children <1 year estimates
      for acute bronchitis were highest. Using a broad definition of virus activity and
      summarising the data for all children diagnosed with ILI, 60% was attributable to
      influenza (40% RSV) as were 37% of episodes diagnosed as acute bronchitis, 9% of
      those with asthma and 48% of those with otitis media. Using a narrow definition,
      corresponding proportions were: for ILI diagnoses 77% (23% RSV), acute bronchitis
      32%, asthma zero, and otitis media 45%. Acute bronchitis was diagnosed twice as
      frequently in association with RSV as with influenza in all age groups: excess
      asthma episodes were only evident in RSV active periods. CONCLUSIONS: Except in
      relation to ILI, RSV caused more illness than the influenza virus in the
      respiratory diagnoses examined, emphasising the need for RSV prevention and
      treatment. Influenza was not associated with excess asthma episodes.

PMID- 15855179
TI  - Is being overweight associated with behavioural problems in childhood and
      adolescence? Findings from the Mater-University study of pregnancy and its
      outcomes.
AB  - AIMS: To examine the associations between being overweight and behavioural
      problems at ages 5 and 14. METHODS: Birth cohort study of 2875 individuals who
      were born in Brisbane between 1981 and 1984 and who were followed up at ages 5
      and 14 years. Behavioural problems were defined as scoring above the 90th centile
      on Achenbach's child behavioural checklist. RESULTS: In cross-sectional analyses
      there was no association between being overweight and behavioural problems in
      either females at age 5. At age 14 females who were overweight were more likely
      than those who were normal weight to experience behavioural problems. However,
      there was no association between being overweight and behavioural problems at age
      14 among males. The prevalence of behavioural problems increased linearly across
      the distribution of body mass index in females at age 14. In prospective
      analyses, among participants who had no behavioural problems at age 5, there was
      no association between being overweight at age 5 and behavioural problems at age
      14 in either sex. Females who were overweight at age 5 and normal weight at age
      14 had reduced odds of behavioural problems at age 14. CONCLUSIONS: Among
      adolescent females there is a positive linear association between body size and
      behavioural problems. However, no such association was found in adolescent males,
      or in either sex at age 5 years, and in prospective analyses being overweight at
      age 5 was not associated with behavioural problems in either sex at age 14.

PMID- 15855180
TI  - How accurate is the diagnosis of exercise induced asthma among Vancouver
      schoolchildren?
AB  - BACKGROUND: Limited access to exercise testing facilities means that the
      diagnosis of exercise induced asthma (EIA) is mainly based on self-reported
      respiratory symptoms. This is open to error since the correlation between
      exercise related symptoms and subsequent exercise testing has been shown to be
      poor. AIM: To study the accuracy of clinically diagnosed EIA among Vancouver
      schoolchildren. METHODS: Fifty two children referred for investigation of poorly
      controlled EIA were studied. Following a careful history and physical
      examination, children performed pulmonary function tests before, then 5 and 15
      minutes after a standardised treadmill exercise test. Based on overall
      assessment, a diagnostic explanation for each child's respiratory complaints was
      provided as far as possible. RESULTS: Only eight children (15.4%) fulfilled
      diagnostic criteria for EIA (fall in FEV(1) > or =10%). Of the remainder: 12
      (23.1%) were unfit, 14 (26.9%) had vocal cord dysfunction/sigh dyspnoea, 7
      (13.5%) had a habit cough, and 11 (21.1%) had no abnormalities on clinical or
      laboratory testing, so were given no diagnosis. Initial reported symptoms of
      wheeze or cough often changed significantly following a careful history,
      particularly among the eight elite athletes. The final complaint was sometimes
      not respiratory, and, in a few cases, was not even associated with exercise.
      CONCLUSIONS: The clinical diagnosis of EIA is inaccurate among Vancouver
      schoolchildren, principally due to the unreliability of their initial exercise
      related complaints. Symptom exaggeration, familiarity with medical jargon, and
      psychogenic complaints are all common. A careful history is essential in this
      population before basing any diagnosis on self-reported respiratory symptoms.

PMID- 15855181
TI  - Adolescent use of the combined oral contraceptive pill: a retrospective
      observational study.
AB  - AIMS: To determine the extent of combined oral contraceptive use by girls aged 10
      16 years in Scotland. METHODS: Assessment of combined oral contraceptive
      prescribing in 35 414 girls for the year 1 November 1999-31 October 2000 from
      data retrieved from 161 primary care practices taking part in the Scottish
      Programme for Improving Clinical Effectiveness in Primary Care, and from national
      aggregated data from family planning clinics. RESULTS: During the study period
      the oral contraceptive pill (OCP) was prescribed by a primary care physician to
      1531 girls (4.3%) aged 10-16 years. The age specific prevalence rates per 1000
      girls registered with their family doctor rose from 0.9/1000 girls aged 12 years
      or younger, to 6.9, 30, 86.3, and 174.8/1000 for girls aged 13, 14, 15, and 16
      years respectively. The overall prevalence of combined oral contraceptive
      prescribing by primary care physicians was 43.2/1000 girls aged 10-16 years. A
      further 1765 girls aged 13-16 years obtained a prescription for the OCP from a
      Scottish family planning clinic, giving an overall prevalence rate for family
      planning clinic prescribing of 8.0/1000 girls aged 10-16 years. Despite
      reportedly high levels of sexual activity and teenage pregnancy in this age
      group, these results confirm that OCP use is relatively low. CONCLUSIONS: The UK
      has the highest rate of teenage pregnancy in Western Europe, but despite the
      medical and social concerns about the sexual health of teenagers, the level of
      oral contraceptive use in this young age group remains low.

PMID- 15855182
TI  - Onset of breast and pubic hair development in 1231 preadolescent Lithuanian
      schoolgirls.
AB  - BACKGROUND: Correct staging of puberty is essential in order to differentiate
      different pathologies, as various components of the endocrine system influence
      breast, pubic, and axillary hair development. AIMS: To determine the current
      timing of adrenarche and breast development in Lithuanian preadolescent
      schoolgirls. METHODS: Cross-sectional study of 1231 schoolgirls aged 7.0-11.6
      years. Puberty was staged according to the method of Tanner. Mean age at entry
      into each pubertal stage was calculated by probit analysis. RESULTS: Of the 255
      girls aged 7 years, two had premature adrenarche (0.8%) and one premature
      thelarche (0.4%). Mean age of onset of pubic/axillary hair development was 11.0
      years, and for breast development (Stage 2) 10.2 years. Breast Stage 3
      development was attained at 11.3 years and Stage 4 at 13.9 years. Mean BMI,
      height, weight, and systolic blood pressure SD scores were higher in pubertal
      than in prepubertal girls. Skinfold thickness was also significantly higher in
      girls with isolated adrenarche than in prepubertal girls. The increase in BMI and
      weight resulted from an increase in body fat as evidenced by measures of
      subscapular and triceps skinfold thickness. Girls with only signs of adrenarche
      or thelarche did not differ from each other from the anthropometric standpoint.
      CONCLUSIONS: Premature thelarche and premature adrenarche were relatively
      uncommon in this population. Pubertal onset was slightly earlier than the UK
      Tanner standards and tended to occur in girls with a higher BMI.

PMID- 15855183
TI  - Pharmacokinetic-pharmacodynamic correlations and biomarkers in the development of
      COX-2 inhibitors.
AB  - The mechanism by which COX inhibitors exert their analgesic effect is well
      established. However, data show no direct correlation between drug concentrations
      in plasma and the analgesic or adverse effects in chronic inflammatory
      conditions. This represents a major problem in the development of COX inhibitors,
      since it is difficult to predict the appropriate dosing regimen for the treatment
      of chronic inflammatory pain, based upon information from pre-clinical studies
      and eventually early clinical studies. The factors that determine response in
      inflammatory pain must be understood in order to make predictions about the time
      course of the analgesic effect. In this review the determinants of drug response
      and their variability will be discussed: physicochemical properties,
      pharmacokinetics (PK), pathophysiology and disease progression. From a
      mechanistic point of view, endogenous mediators of inflammation might be used as
      a biomarker for the analgesic effect and safety assessment. Such a biomarker can
      be an intermediate step between drug exposure and response. In addition, its
      concentration-effect relationship could be characterized by pharmacokinetic
      pharmacodynamic (PK/PD) modelling. Indeed, recent investigations have shown that
      COX-2 inhibition, as determined by modelling of prostaglandin E2 (PGE2) levels in
      the whole blood assay in vitro can be used as a marker to predict drug effects
      (analgesia) in humans. A model-derived parameter, IC80, (total and unbound) was
      found to correlate directly with the analgesic plasma concentration of different
      COX inhibitors varying in enzyme selectivity. These findings indicate that PGE2
      and thromboxane B2 inhibition can be used to predict and select efficacious doses
      in humans.

PMID- 15855184
TI  - Chronic lymphocytic leukaemia and concomitant relapsing polychondritis: a report
      on one treatment for the combined manifestation of two diseases.

PMID- 15855185
TI  - Rheumatological manifestations of hepatitis C: incidence in a rheumatology and
      non-rheumatology setting and the effect of methotrexate and interferon.
AB  - OBJECTIVES: To evaluate hepatitis C virus (HCV)-positive patients followed in a
      rheumatology department and to compare them with a similar population of HCV
      positive patients who had never seen a rheumatologist, in order to describe the
      rheumatological symptoms present and the effects of methotrexate and interferon
      alpha therapy. METHODS: We performed a retrospective study of clinical,
      radiological and biological data on 21 rheumatology patients (Group I) presenting
      symptoms consistent with a chronic inflammatory arthritis with a known HCV
      infection and compared them with 41 members of an HCV support association (Group
      II). RESULTS: Symptoms of myalgia, sicca syndrome, Raynaud's phenomenon or
      paraesthesias were similarly frequent in the two groups. However, inflammatory
      joint pain and joint swelling were more common in Group I. In this group
      rheumatoid factor was positive in 48%, antinuclear antibodies in 26%,
      cryoglobulin in 44% and a reduced complement level in 63%. The majority of
      patients from Group I treated with methotrexate demonstrated an amelioration of
      the rheumatological symptoms with few negative outcomes. Regarding interferon
      alpha therapy and rheumatological symptoms-in Groups I and II respectively 50 and
      66% demonstrated a deterioration, 33 and 30% showed no change and 17 and 4%
      showed an amelioration. CONCLUSION: Rheumatological symptoms are common in
      patients chronically infected with HCV. It is essential to individualize the role
      of treatment with interferon-alpha and to consider the use of methotrexate for
      difficult cases.

PMID- 15855186
TI  - The response to anti-TNF-alpha treatment: gene regulation at the bedside.

PMID- 15855187
TI  - Etanercept and uveitis in patients with juvenile idiopathic arthritis.
AB  - OBJECTIVES: Etanercept has been shown to be effective for the treatment of
      juvenile idiopathic arthritis (JIA). The therapeutic efficacy of etanercept for
      chronic uveitis, a major complication of JIA, has not been evaluated so far.
      Therefore, the appearance of chronic anterior uveitis and associated
      complications in JIA patients treated with etanercept was evaluated. METHODS:
      Questionnaires were sent to paediatric rheumatologists treating a total of 310
      JIA patients with etanercept. RESULTS: Two hundred and twenty-nine questionnaires
      (74%) were returned. Before institution of etanercept, 31 patients (13.5%) had a
      history of uveitis with a total of 102 flares. Twenty-eight patients belonged to
      the high-risk groups of the oligoarticular and seronegative polyarticular
      subtypes. Upon commencing etanercept, 32 courses of uveitis occurred in 19
      patients and in two further patients (1%) in whom uveitis occurred for the first
      time. Twenty of them belonged to the high-risk group. Uveitis during etanercept
      therapy occurred in 12 of 15 patients (80%) with more than one course of uveitis,
      and in seven of 16 patients (44%) with only one course before etanercept therapy.
      Complications were noted in 12 patients before and in eight during etanercept
      treatment. In 87% of the uveitis patients, arthritis demonstrated a significant
      or complete response. CONCLUSION: During treatment with etanercept, there were
      both relapses and first courses of uveitis. In addition, the frequency and
      severity of uveitis seemed not to be influenced by etanercept. In particular,
      patients with relapsing uveitis before institution of etanercept treatment remain
      at high risk of the development of uveitis flares despite etanercept treatment.

PMID- 15855188
TI  - Screening with the exercise test: time for a guideline change?

PMID- 15855189
TI  - Therapeutical potential of blood-derived progenitor cells in patients with
      peripheral arterial occlusive disease and critical limb ischaemia.
AB  - AIMS: Despite considerable advances in the therapy of patients with peripheral
      arterial occlusive disease (PAOD) and critical limb ischaemia (CLI), a
      substantial number remain, in whom amputation has to be considered the only and
      final option. Recent evidence from animal models of hind limb ischaemia suggests
      that neovascularization induced by circulating blood-derived progenitor cells
      (CPCs) may permit limb salvage. It remains unclear, however, whether an intra
      arterial application of autologous CPCs in patients with infrapopliteal PAOD and
      CLI is safe, feasible, and of potentially beneficial effects. METHODS AND
      RESULTS: Seven patients with critical PAOD were treated with an intra-arterial
      infusion of autologous CPCs (39+/-24 x 10(6)) isolated from peripheral blood. Pre
      interventional stimulation with G-CSF and CPC application was well tolerated.
      Twelve weeks after CPC administration, the pain-free walking distance increased
      from 6+/-13 to 195+/-196 m. A significant increase in the ankle-brachial index,
      transcutaneous O(2), flow-dependent vasodilation, flow reserve in response to
      adenosine, and endothelium-dependent vasodilation was observed. CONCLUSION: These
      preliminary data in a small series of patients with CLI without surgical or
      interventional options indicate that CPC application is safe, feasible, and may
      improve both functional and clinical indices.

PMID- 15855190
TI  - Effect of thrombolytic therapy on the risk of cardiac rupture and mortality in
      older patients with first acute myocardial infarction.
AB  - AIMS: To evaluate the effect of thrombolysis on mortality and its causes in older
      patients with acute myocardial infarction (AMI). METHODS AND RESULTS: An analysis
      of 706 consecutive patients > or =75 years old with a first AMI enrolled in the
      PPRIMM75 registry showed that although there were important differences in
      baseline characteristics among patients treated with thrombolysis, primary
      angioplasty (PA) and those who did not receive reperfusion therapy, 30 day
      mortality did not differ (29, 25, and 32%, respectively). The main cause of death
      in patients treated with thrombolysis was cardiac rupture (54%), whereas most of
      the other patients died in cardiogenic shock. Patients who received thrombolysis
      had a higher (P<0.0001) incidence of free wall rupture (FWR) (17.1%) compared
      with those who did not receive reperfusion therapy (7.9%) or who underwent PA
      (4.9%). By multivariable analysis, patients treated with thrombolytic therapy
      (TT) showed an excess risk of FWR (OR, 3.62; 95% CI, 1.79-7.33), a hazard not
      observed in patients who underwent PA. When compared with patients who did not
      receive reperfusion therapy, the odds ratio of 30 day mortality was 1.07 (95% CI,
      0.65-1.76) for patients treated with thrombolysis and 0.78 (95% CI, 0.45-1.34)
      for those who underwent PA. The figures for 24 month mortality were 0.78 (95% CI,
      0.65-1.76) and 0.67 (95% CI, 0.28-0.81), respectively. CONCLUSION: Treatment of
      first AMI with TT increases the risk of FWR in very old patients, a risk not
      observed in patients treated with PA.

PMID- 15855191
TI  - Dendritic cells in atherosclerosis: current status of the problem and clinical
      relevance.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells. DCs were
      identified in arteries in 1995 and, since then, further knowledge has been gained
      indicating the importance of DCs in atherosclerosis. Vascular DCs have been shown
      to become activated from a very early stage of atherosclerosis. Some DCs cluster
      with T cells directly within atherosclerotic lesions, while others migrate to
      lymphoid organs to activate T cells. Dyslipidaemia systemically alters DC
      function and recent findings suggest that DCs play a role in plaque
      destabilization. This review summarizes the current status of the problem.

PMID- 15855192
TI  - Pulmonary haemodynamics at rest and during exercise in patients with significant
      pulmonary vein stenosis after radiofrequency catheter ablation for drug resistant
      atrial fibrillation.
AB  - AIMS: Iatrogenic pulmonary vein (PV) stenosis after radiofrequency catheter
      ablation for atrial fibrillation (AF) is a new pathology in cardiology. The
      effects of PV stenosis on the pulmonary circulation are not yet known. We provide
      long-term follow-up data in patients with significant PV stenosis including
      magnetic resonance imaging (MRI) and Swan Ganz (SG) right heart catheterization.
      METHODS AND RESULTS: One hundred and seventeen patients had MRI 12-24 months
      after the AF ablation procedure. Eleven patients (58+/-7 years, nine males) with
      significant stenosis (n=9) or occlusion of the proximal PV (n=5) at this follow
      up were re-examined using MRI and SG right heart catheterization at rest and
      during exercise (follow-up time since PV ablation 50+/-15 months). None of these
      underwent previous PV angioplasty. When compared with prior MRI studies, no
      significant changes were noted. At rest, no patient had pulmonary hypertension.
      At 100 W, seven patients had elevated pulmonary artery pressures, three of them
      probably caused, in part, by left ventricular dysfunction. CONCLUSION:
      Significant stenosis/occlusions of one or two PV do not create pulmonary
      hypertension at rest during long-term follow-up. However, seven of the 11
      patients develop pulmonary hypertension during exercise. All three patients with
      stenosis/occlusions of two PV were affected.

PMID- 15855193
TI  - Reasons for terminating an exercise test provide independent prognostic
      information: 2014 apparently healthy men followed for 26 years.
AB  - AIMS: We wanted to study whether reasons for terminating an exercise test might
      influence long-term mortality of healthy men, a previously unreported subject.
      METHODS AND RESULTS: During 1972-75, 2014 men aged 40-59, free from somatic
      diseases and not using drugs, underwent an examination programme including case
      history, clinical examination, various blood tests, and a symptom limited
      exercise ECG-test. The following reasons for test termination were noted:
      impaired breathing, lower limb fatigue, exhaustion (=combined lower limb fatigue
      and impaired breathing), high heart rate, abnormal blood pressure response, heart
      arrhythmias, increasing chest pain during exercise, marked ST-depressions during
      the test, and refusal to continue. Follow-up was 26 years. When adjusting for
      age, men who stopped exercising exclusively because of impaired breathing (n=178)
      had a 1.86-fold increased risk (95% CI 1.34-2.60; P=0.0002) of dying from
      coronary heart disease (CHD), a 1.64-fold increased risk (95% CI 1.32-2.03;
      P<0.0001) of dying from any cause, and a 3.47-fold increased risk (95% CI 2.24
      5.12; P<0.0001) of dying from pulmonary causes compared with men having defined
      exhaustion (n=1376). After adjustment for age, smoking, total serum cholesterol,
      fasting blood glucose, systolic blood pressure, and physical fitness, impaired
      breathing remained significantly associated to an increased risk of dying from
      CHD, pulmonary disease, or any causes. CONCLUSION: Healthy men who stop bicycle
      exercising only because of impaired breathing have a high long-term CHD-,
      pulmonary-, and total-mortality, and such men may need further diagnostic
      scrutiny and follow-up.

PMID- 15855194
TI  - Utility of serum C-reactive protein in assessing the outcome of infective
      endocarditis.
AB  - AIMS: To evaluate the diagnostic usefulness of serial serum C-reactive protein
      determinations in monitoring the outcome of infective endocarditis (IE). METHODS
      AND RESULTS: C-reactive protein, erythrocyte sedimentation rate (ESR), and white
      blood cell count (WBC) were measured from admission until week 10 in 129 patients
      with 134 episodes of IE. Need for cardiac surgery and final outcome were assessed
      until 3 months from admission. Data were evaluated using extensive statistical
      analyses. The fall in serum C-reactive protein or WBC was significantly faster
      when a patient had an uncomplicated recovery than when complications developed or
      death ensued, but no such behaviour was observed in ESR. None of the 80 patients
      who had normal C-reactive protein by week 10 died of IE. Moreover, none of the 22
      patients who had normal C-reactive protein by week 4 needed cardiac surgery and
      only two of the 33 patients who had normal C-reactive protein by week 6 needed
      cardiac surgery, both after successful medical treatment of IE. Of the 87
      patients whose WBC normalized within 4 weeks, six died and 15 needed valve
      surgery. CONCLUSION: The normalization of C-reactive protein proved to be a good
      predictor of a favourable late outcome (surgery, death) of IE. Also WBC count
      proved useful in the assessment of patients with IE, but the value of ESR was
      negligible.

PMID- 15855195
TI  - Histopathology of intraoperatively induced linear radiofrequency ablation lesions
      in patients with chronic atrial fibrillation.
AB  - AIMS: Radiofrequency (RF) energy has been extensively used in ablation of
      arrhythmia but so far no analysis of morphological effects in human left atria
      has been conducted. METHODS AND RESULTS: We studied 59 ablation lesions from
      seven patients who died 2 to 22 days after open heart surgery plus intraoperative
      cooled-tip RF ablation to treat permanent atrial fibrillation (AF) (mean 4, 1-11
      years). The ablation area was studied by macroscopy and histological analysis. RF
      ablation produced clearly delineated coagulation necrosis (up to a depth of 5.5
      mm) bordered by an irregular zone of incomplete necrosis and fresh bleeding even
      22 days post-operatively. No superficial charring, thrombotic deposition, or
      perforation was documented. Endocardium and subendocardium displayed oedematic
      loosening and microfragmentation of connective tissue fibres. Early after
      ablation (2-6 days), interfibrillar disseminated bleeding and necrosis without
      tissue removal response were found. Later after ablation (21, 22 days), mild
      inflammatory reaction and granulation tissue appeared. Twenty-five per cent of
      all studied lesions, especially in the thick region in between left pulmonary
      veins and mitral annulus (left atrial isthmus) (86%), were non-transmural. Nerve
      fibres with different degrees of thermal injury were detected in the pulmonary
      vein ostial region. CONCLUSION: Intraoperative cooled-tip ablation in AF resulted
      in coagulation necrosis of endocardium, subendocardium, and the atrial myocardial
      layer to a depth of 5.5 mm bordered by an irregular zone of incomplete thermal
      damage. Transmurality of the lesions could only be found in 75% of
      intraoperatively applied lesions.

PMID- 15855196
TI  - Salt loss and hyponatraemia in a patient with syphilitic nephritis.

PMID- 15855197
TI  - Complication after embolization of a complex renal vascular malformation.

PMID- 15855198
TI  - Two cases of delayed cyclosporin absorption leading to CsA exposure higher than
      that predicted by C2 monitoring alone.

PMID- 15855199
TI  - The donation process of living kidney donors.
AB  - BACKGROUND: The rates of both genetic and non-genetic living donors are
      increasing. However, previous research has almost exclusively explored the
      decision-making of genetic donors. Therefore, in this study both genetic and non
      genetic donors are investigated with focus on their whole donation process.
      METHODS: Thirty-nine donors were interviewed the day before nephrectomy and 3
      weeks afterwards. Twenty-three donors were genetic relatives, 16 were not. The
      interviews were analysed qualitatively, mainly by narrative structuring. RESULTS:
      All donors but one passed seven steps in the donation process. They included: (i)
      awareness of suffering; compassion and empathy; (ii) imminence of
      transplantation; recognition of oneself as potential donor; (iii) information
      acquisition and deliberation; (iv) attribution of responsibility to oneself;
      announcement of decision to donate; (v) examination; maintaining the decision;
      (vi) facing nephrectomy; and (vii) postoperative experiences. Two types of
      decision-making were displayed: immediate and later announcement of decision.
      Half the donors belonged to each type. Various relationship groups displayed
      different types. The examination period was the most stressful time, partly due
      to imperfect coordination and excessive time-wasting. One-third found
      postoperative pain the most painful experience ever. There was a lack of
      attention to regressive needs and to recognition of the deed. CONCLUSIONS: The
      two types of decision-making seem similar in ethical requirements. It is not a
      genetic or non-genetic relationship per se that determines what kind of decision
      the donors make. Psychological support, especially during Steps 5 and 7, should
      be improved and the donors included in a structured donation programme. Possible
      health care ambivalence toward living donation should not affect the donors.

PMID- 15855200
TI  - The impact of topical mupirocin on peritoneal dialysis infection rates in
      Singapore General Hospital.
AB  - BACKGROUND: Peritonitis and exit-site infections (ESI) are major causes of
      technique failure and morbidity in peritoneal dialysis (PD) patients. Topical
      mupirocin on the exit-site has been shown to reduce such complications and
      prolong life in PD. Since the year 2000, such an approach has been adopted for
      our new incident PD population. We now report the results of this new protocol.
      We also studied the effect of co-morbidity on peritonitis occurrence. METHODS: A
      total of 740 incident PD patients were studied. Patients were divided into two
      groups based on year of entry into PD (Group 1 from January 1998-December 1999
      without topical mupirocin and Group 2 from January 2000-March 2004 with topical
      mupirocin). Variables studied included gender, age, diabetic status, ischaemic
      heart disease, peripheral vascular disease, cerebrovascular disease and serum
      albumin. RESULTS: Topical mupirocin at the exit-site has led to a significant
      reduction in peritonitis rate (0.443 vs 0.339 episodes/patient-year; P<0.0005)
      and ESI (0.168 vs 0.156 episodes/patient-year; P<0.005) attributed primarily to
      the significant reduction in Staphylococcus aureus infections. There was an
      unexpected finding of lower Pseudomonas aeruginosa peritonitis in the mupirocin
      group (P<0.005). Stepwise multiple logistic regression analysis revealed that
      only mupirocin application and serum albumin were significant predictors of
      peritonitis. CONCLUSIONS: Our study, although limited by its retrospective
      nature, demonstrated that topical mupirocin was associated with a significant
      reduction in ESI and peritonitis with unexpected findings of lower Pseudomonas
      peritonitis. Serum albumin prior to the initiation of PD was a strong predictor
      of subsequent peritonitis. Mupirocin, with its low toxicity, ease of application
      and demonstrable beneficial effect in reducing ESI and peritonitis is now used on
      all incident PD patients.

PMID- 15855201
TI  - Simvastatin attenuates renal inflammation, tubular transdifferentiation and
      interstitial fibrosis in rats with unilateral ureteral obstruction.
AB  - BACKGROUND: The pleiotropic actions of statins have been largely explored. These
      drugs have been tested in several models of progressive renal disease, most of
      them accompanied by hypertension. We sought to investigate more closely the
      effects of simvastatin on renal interstitial fibrosis due to unilateral ureteral
      obstruction (UUO). METHODS: Munich-Wistar rats were submitted to UUO and studied
      after 14 days. Animals were divided into two groups: vehicle (VH) or simvastatin
      (SIMV) 2 mg/kg b.i.d. by gavage. At sacrifice kidneys were harvested for
      morphology, mRNA and protein analysis. RT-PCR was done to assess expression of
      collagen I and III, fibronectin, MCP-1, TGF-beta1 and bFGF. Protein expression
      was assessed by western blot (TGF-beta) and immunostaining (macrophage,
      lymphocyte, PCNA, vimentin and alpha-smooth muscle actin). Contralateral kidneys
      (CL) were used as controls. RESULTS: SIMV-treated animals had less severe renal
      inflammation. MCP-1 was markedly expressed in obstructed kidneys and diminished
      with SIMV (48.9+/- 2.5 vs 64.3+/-3.1 OD in VH, P<0.01). Interstitial fibrosis
      (IF) was significantly attenuated with SIMV (8.2+/-1.3 vs 13.2+/-0.6%, P<0.01
      SIMV vs VH), which was confirmed by a decrease in collagen I and fibronectin
      renal expression. Vimentin, a marker of dedifferentiation, was expressed in
      tubular cells of VH and decreased with SIMV treatment. alpha-SMA, a marker of
      myofibroblast-type cells, was increased in renal interstitium of VH rats and SIMV
      significantly reduced its expression. PCNA was increased in the UUO kidneys, but
      SIMV did not decrease tubular or interstitial proliferating cells. TGF-beta1,
      which was highly induced in the obstructed kidneys, decreased at the post
      transcriptional level with SIMV treatment (5.35+/-0.75 vs 13.10+/-2.9 OD in VH,
      P<0.05). bFGF mRNA was also overexpressed in the obstructed kidneys, although
      SIMV treatment did not significantly decrease its expression. CONCLUSIONS: SIMV
      had an evident protective effect on renal interstitial inflammation and fibrosis.
      It is conceivable that by attenuating inflammation, SIMV prevented tubular
      activation and transdifferentiation, two processes largely involved in the renal
      fibrosis of the UUO model.

PMID- 15855202
TI  - Prevalence of chronic renal failure in adults in Delhi, India.
AB  - BACKGROUND: Chronic renal failure (CRF) is a debilitating condition responsible
      for high morbidity and mortality and is a financial burden on government and
      society. Because of its costs and the complexity of its treatment, proper care is
      available to very few patients in India. A community-based study has not been
      done to determine the prevalence of CRF in India. METHODS: We used a multi-stage
      cluster sampling method in the South Zones of Delhi. In each area, we first
      contacted the local social leader and explained the study and the medical
      information pamphlets. On pre-scheduled days, the study team canvassed the study
      zone. The individuals contacted responded to a detailed questionnaire, and had a
      physical examination, a dipstick urine test for albumin and sugar and a blood
      test for serum creatinine. A serum creatinine >1.8 mg% defined renal failure. A
      repeat test for serum creatinine was done after 8-12 weeks to confirm chronicity
      of renal failure. If it was >1.8 mg% after 3 months in the absence of reversible
      factors, CRF was diagnosed. The person found to have CRF was asked to attend a
      hospital renal clinic for further investigations and individualized management.
      RESULTS: A total of 4972 persons were contacted for the study. Their mean age was
      42+/-13 years; 56% were males. Out of the 4972 who were initially approached,
      4712 agreed to give the blood sample, and thus were included for the evaluation
      of CRF. CRF was found in 37 of them. Thus, the prevalence of CRF in that adult
      population was 0.785% or 7852/million. CONCLUSIONS: The prevalence of CRF in
      India makes it a serious problem in need of urgent efforts to contain it.

PMID- 15855203
TI  - The true history of home haemodialysis.

PMID- 15855204
TI  - Elevated concentrations of cardiac troponins are associated with severe coronary
      artery calcification in asymptomatic haemodialysis patients.

PMID- 15855205
TI  - Diverse effects of natural antioxidants on cyclosporin cytotoxicity in rat renal
      tubular cells.
AB  - BACKGROUND: As is well known, the use of the immunosuppressive drug cyclosporin A
      (CsA) is partially restricted by its nephrotoxic effects, which include early
      changes in haemodynamics followed by irreversible injuries to the renal tubules.
      Although the mechanisms responsible for these side effects are poorly understood,
      an involvement of reactive oxygen species (ROS) has been suggested. In this
      study, we selected three natural antioxidants, resveratrol, hydroxytyrosol and
      vitamin E, on the basis of their scavenging capabilities, and tested their
      protective effects against CsA toxicity. METHODS: Immortalized rat tubular cells
      (RPTc) were used as the model system. Cell viability was checked with trypan blue
      assay, and free radical formation was measured using the fluorescent probe 2,7
      dichlorofluorescein (DCF). We evaluated several oxidative stress parameters,
      including phospholipid peroxidation products, glutathione levels and oxygenase
      expression. RESULTS: Incubation of RPTc with 25 muM CsA induced a significant
      decrease in cell viability paralleled by intracellular ROS formation and
      alterations in lipid peroxidation. There was also an imbalance of glutathione
      redox state as well as upregulation of heme oxygenase-1 (HO-1). The three
      antioxidants, at micromolar concentration, quantitatively prevented the ROS
      activated DCF fluorescent signal and membrane lipid peroxidation. Both
      hydroxytyrosol and resveratrol strengthened the CsA induction of HO-1 expression.
      Moreover, vitamin E and resveratrol counteracted CsA-induced changes in the
      glutathione redox state via different mechanisms, whereas hydroxytyrosol was
      completely ineffective. Similarly, CsA-dependent nephrotoxicity was prevented by
      vitamin E, while resveratrol only exerted partial protection, and hydroxytyrosol
      showed no protective effects. CONCLUSION: Our results indicate that the diverse
      cytoprotective effects of the antioxidants tested in these studies were not
      directly related to their scavenging capabilities. These findings confirm a key
      role for glutathione in protecting cells from CsA-induced adverse effects and do
      not support a direct link between CsA-mediated ROS generation and adverse renal
      effects.

PMID- 15855206
TI  - Estimation of heparin leak into the systemic circulation after central venous
      catheter heparin lock.
AB  - BACKGROUND: Although most catheter problems in haemodialysis are related to
      infection or clotting, bleeding associated with the heparin lock is of clinical
      importance especially during peri-operative conditions. The objective of this in
      vitro study is to estimate the volume of heparin that may leak into the
      circulation immediately after performing a catheter lock. METHODS: Different
      volumes (ml) of a dextrose solution were used to perform a catheter lock on
      haemodialysis catheters. The tip of the catheter was placed in a test tube
      containing water for a pre-specified period. The final concentrations of dextrose
      in the test tube were used to determine the volume of solution that leaked from
      the catheter. RESULTS: When the total lumen volume was filled, the catheter leak
      was estimated to be 0.59+/-0.03 and 0.71+/-0.04 ml after 15 and 25 s,
      respectively. There was a continuous leak of 1.23+/-0.41, 2.20+/-0.34 and 3.38+/
      0.23 ml at 5, 15 and 30 min, respectively, after performing a catheter lock on a
      catheter with a total lumen volume of 4.5 ml. The catheter leak was significantly
      reduced when only 3.7 ml of solution was used to fill the total lumen volume of
      4.5 ml. CONCLUSION: The present study demonstrates a significant early and late
      leakage from the catheter that occurs after performing a catheter lock. When
      applied to heparin, the volume of the unwanted catheter leak may result in
      adverse clinical events, especially following haemodialysis sessions and during
      peri-operative periods. However, these results are hypothesis-generating, and
      clinical studies are necessary to evaluate the efficacy of underfilling.

PMID- 15855207
TI  - Measured creatinine clearance from timed urine collections substantially
      overestimates glomerular filtration rate in patients with liver cirrhosis: a
      systematic review and individual patient meta-analysis.
AB  - BACKGROUND: Accurate glomerular filtration rate (GFR) assessment in patients with
      liver cirrhosis is important for prognostication, chronic kidney disease staging,
      drug dosing and identifying combined liver-kidney transplantation candidates. The
      objective of this study was to review the accuracy of measured creatinine
      clearance (MCrCl) from timed urine collections for estimating true GFR. METHODS:
      A systematic review and individual patient meta-analysis was performed. MEDLINE,
      old MEDLINE, Index Medicus and Cochrane library bibliographic databases and
      conference proceedings were searched up to June 2004. Reference lists of relevant
      studies were searched and experts were contacted. Comparative diagnostic studies
      describing stable adult patients with cirrhosis categorized according to the
      Child-Pugh classification were included if a gold standard GFR measurement was
      performed within 3 days of MCrCl. Individual patient data were abstracted from
      graphs of primary articles to allow a pooled analysis of agreement between renal
      measures. RESULTS: Seven studies of 193 patients from 1974 to 2002 were
      summarized. MCrCl overestimated inulin clearance (CIn) by a mean of +13
      ml/min/1.73 m2 and the limits of agreement (mean of the differences+/-2 SD) were
      +60 ml/min/1.73 m2 and -34 ml/min/1.73 m2. This overestimation was highest in
      patients with lower GFR. The mean clearance ratios [95% confidence interval (CI)]
      between MCrCl and CIn in the high (> or =60 ml/min/1.73 m2) and low (<60
      ml/min/1.73 m2) GFR subgroups were 1.18 (1.12-1.23) and 1.49 (1.33-1.66),
      respectively (P<0.0001). Fourteen percent of patients with a MCrCl > or =60
      ml/min/1.73 m2 had a CIn of <30 ml/min/1.73 m2. CONCLUSIONS: For patients with
      liver cirrhosis, MCrCl from timed urine collections consistently overestimates
      the true GFR. For patients requiring complete clinical evaluation, GFR assessment
      by CIn is justified.

PMID- 15855208
TI  - 1,25-Dihydroxyvitamin D3 but not cinacalcet HCl (Sensipar/Mimpara) treatment
      mediates aortic calcification in a rat model of secondary hyperparathyroidism.
AB  - BACKGROUND: Calcitriol treatment of secondary hyperparathyroidism (HPT) in
      chronic kidney disease (CKD) patients can lead to increased serum calcium and
      phosphorus, which have been associated as risk factors for vascular
      calcification. Cinacalcet HCl (Sensipar/Mimpara) {(alphaR)-(-)-alpha-methyl-N-[3
      [3-(trifluoromethylphenyl)propyl]-1-napthalenemethanamine hydrochloride} lowers
      serum parathyroid hormone (PTH), calcium, phosphorus and calcium-phosphorous
      (CaxP) product in stage 5 CKD dialysis patients; however, its effects on vascular
      calcification are unknown. METHODS: Cinacalcet HCl (10 or 1 mg/kg, p.o. gavage),
      1,25-dihydroxyvitamin D(3) (0.1 microg, s.c, calcitriol) or the combination was
      administered daily for 26 days in a rat model of secondary HPT [5/6 nephrectomy].
      After dosing, aortic calcification was determined using the von Kossa staining
      method. Serum PTH and blood chemistries were determined on days 0, 26 and 0, 14,
      26, respectively, prior to and after dosing. RESULTS: Calcitriol-treated rats had
      moderate to marked aortic calcification, whereas no significant calcification was
      observed in vehicle- or cinacalcet HCl-only treated groups. Co-administration of
      cinacalcet HCl with calcitriol did not attenuate the calcitriol-mediated increase
      in CaxP product or calcitriol-mediated aortic calcification. Both calcitriol and
      cinacalcet HCl therapy significantly reduced serum PTH levels. Calcitriol
      significantly elevated serum calcium, serum phosphorous and CaxP product above
      pretreatment levels, or those seen with vehicle or cinacalcet HCl. Cinacalcet HCl
      (10 or 1 mg/kg) decreased serum ionized calcium and decreased calcitriol-induced
      hypercalcaemia. CONCLUSION: Cinacalcet HCl and calcitriol both effectively reduce
      PTH, albeit via different mechanisms, but unlike calcitriol, cinacalcet HCl did
      not produce hypercalcaemia, an increased CaxP product or vascular calcification.

PMID- 15855209
TI  - ANCA-negative pauci-immune renal vasculitis: histology and outcome.
AB  - BACKGROUND: Pauci-immune renal vasculitis with focal glomerular necrosis and
      crescent formation is usually associated with anti-neutrophil cytoplasmic
      antibodies (ANCAs). However, ANCA's are absent in up to 10% of cases, which
      constitutes a rarely studied variant of renal vasculitis. METHODS: This
      retrospective multicentre cohort study analyzed the presenting features, renal
      histology and outcome in 20 patients with pauci-immune crescentic necrotizing
      renal vasculitis in whom indirect immunofluorescence did not detect ANCA.
      RESULTS: Renal histology revealed a high percentage of active glomerular lesions
      (50%), mainly cellular crescents, 28% of them with glomerular necrosis. Chronic
      tissue damage with glomerulosclerosis (21%) and diffuse interstitial fibrosis
      (40%) was already present at diagnosis, more prominent than in historical PR3
      positive patients. Infiltrates of polymorphonuclear neutrophils in glomerular
      capillary loops were observed in 40% of all biopsies, mainly in necrotic lesions.
      The subsets of interstitially infiltrating leukocytes similar to ANCA-associated
      disease. Microscopic polyangiitis was diagnosed in 17 patients, Wegener's
      granulomatosis in two and renal-limited vasculitis in one. The patients median
      disease extent index (DEI) of 5 (range 4-11) reflected a systemic vasculitis.
      ANCA-negative vasculitis was not associated with infection or malignancy. Renal
      outcome was correlated to DEI (P = 0.032) and serum creatinine at diagnosis (P =
      0.04). The mortality rate was high (35%) and closely related to age above 65
      years at diagnosis (P = 0.014). Conclusions. The histological findings and
      prognosis in ANCA-negative renal vasculitis are comparable with those of ANCA
      positive disease. Our data underline the importance of the exact diagnosis in an
      active vasculitic disease process even in the absence of ANCAs.

PMID- 15855210
TI  - Hypersensitivity reactions and deaths associated with intravenous iron
      preparations.
AB  - BACKGROUND: Parenteral iron therapy is an accepted adjunctive management of
      anaemia in kidney disease. Newer agents may have fewer severe hypersensitivity
      adverse events (AE) compared with iron dextrans (ID). The rate of type 1 AE to
      iron sucrose (IS) and sodium ferric gluconate (SFG) relative to ID is unclear. We
      used the US Food and Drug Administration's Freedom of Information (FOI)
      surveillance database to compare the type 1 AE profiles for the three intravenous
      iron preparations available in the United States. METHODS: We tabulated reports
      received by the FOI database between January 1997 and September 2002, and
      calculated 100 mg dose equivalents for the treated population for each agent. We
      developed four clinical categories describing hypersensitivity AE (anaphylaxis,
      anaphylactoid reaction, urticaria and angioedema) and an algorithm describing
      anaphylaxis, for specific analyses. RESULTS: All-event reporting rates were 29.2,
      10.5 and 4.2 reports/million 100 mg dose equivalents, while all-fatal-event
      reporting rates were 1.4, 0.6 and 0.0 reports/million 100 mg dose equivalents for
      ID, SFG and IS, respectively. ID had the highest reporting rates in all four
      clinical categories and the anaphylaxis algorithm. SFG had intermediate reporting
      rates for urticaria, anaphylactoid reaction and the anaphylaxis algorithm, and a
      zero reporting rate for the anaphylaxis clinical category. IS had either the
      lowest or a zero reporting rate in all clinical categories/algorithm.
      CONCLUSIONS: These findings confirm a higher risk for AE, especially serious type
      1 reactions, with ID therapy than with newer intravenous iron products and also
      suggest that IS carries the lowest risk for hypersensitivity reactions.

PMID- 15855211
TI  - A journey in reversing practice patterns: a multidisciplinary experience in
      implementing DOQI guidelines for vascular access.
AB  - BACKGROUND: The National Kidney Foundation has established detailed guidelines
      due to increasing morbidity and costs related to haemodialysis vascular access in
      the end-stage renal disease population. METHODS: A quality assurance
      multidisciplinary committee was formed to implement the Dialysis Outcome Quality
      Initiative (DOQI) guidelines in September, 1999. Beginning January 2000, a 'Save
      the Vein Programme' was implemented and native fistulae became the angioaccess of
      first choice for new patients. In addition, an effort was made to replace failed
      non-autogenous vascular accesses with autogenous fistulae. Shortly after, pre
      operative evaluation of the vascular anatomy of the arm by Doppler ultrasound
      became the standard of care. The 1 year period prior to January 2000 was used for
      comparison. RESULTS: Total fistula creation in the year 1999 was 48. In the first
      year after the Save the Vein Programme was begun, 77 new fistulae were created
      and 96 fistulae in the following year. Concurrently, 50 grafts were constructed
      in 1999; this number decreased to 46 in 2000 and to 15 in 2001. The percentage of
      functional fistulae in incident patients increased from 20 to 60% (P<0.001).
      Similarly, in prevalent patients, functional fistulae increased from 24 to 44%
      (P<0.004). For all patients, there was a reduction in the hospitalization rate
      from 98 to 79% (P<0.001) and of vascular-related admissions from 67 to 53%.
      CONCLUSION: A reversal in practice pattern from graft to fistulae creation was
      achieved by the successful implementation of DOQI guidelines. This also resulted
      in a reduction in morbidity.

PMID- 15855212
TI  - Multi-centre evaluation of anticoagulation in patients receiving continuous renal
      replacement therapy (CRRT).
AB  - BACKGROUND: Heparin (hepACG) and regional citrate anticoagulation (citACG) remain
      the most commonly reported continuous renal replacement therapy (CRRT) ACG
      methods employed. No prospective multi-centre published data exist that compare
      different ACG methods with respect to CRRT filter life span or patient
      complications. METHODS: A total of 138 patients from seven US centres receiving
      18 208 h of CRRT comprising a total of 442 CRRT circuits were utilized to assess
      filter life span and ACG-related complications in patients receiving CRRT with
      hepACG, citACG or no ACG (noACG). RESULTS: Mean circuit life was 41.2+/-30.8 h.
      Mean circuit survival was no different for circuits receiving hepACG (42.1+/-27.1
      h) and citACG (44.7+/-35.9 h), but was significantly lower for circuits with
      noACG (27.2+/-21.5 h, P<0.005). Kaplan-Meier analyses revealed no survival
      difference between hepACG and citACG circuits, but significantly lower survival
      for noACG circuits (P<0.001). Log-rank analysis showed that 69% of hepACG and
      citACG circuits whereas only 28% of noACG were functional at 60 h. Clotting rates
      were similar for hepACG circuits (58 out of 230, 25%) and citACG circuits (43 out
      of 158, 27%), but were significantly higher for noACG circuits (27 out of 54,
      50%, P < 0.001). Life-threatening bleeding complications attributable to ACG were
      noted in the hepACG group but were absent in the citACG group. CONCLUSIONS: The
      current analysis represents the largest evaluation of CRRT ACG methods to date.
      While the standard hepACG and citACG methods studied in the prospective
      paediatric CRRT registry led to similar filter life spans and were superior to
      noACG, our data suggest that citACG may result in less life-threatening
      complications.

PMID- 15855213
TI  - Short-term rosiglitazone treatment in renal transplant recipients.

PMID- 15855214
TI  - Cost-effectiveness of irbesartan in diabetic nephropathy: a systematic review of
      published studies.
AB  - BACKGROUND: To review published studies on the cost-effectiveness of the use of
      irbesartan for treatment of advance overt nephropathy in patients with type 2
      diabetes and hypertension. METHODS: Articles were identified based on a search of
      the PubMed databases using the keywords 'irbesartan', 'ESRD', 'cost
      effectiveness', 'nephropathy' and 'costs', and by personal communication with the
      authors. Only studies published in the last 10 years were included. All costs
      data from the cost-effectiveness studies were inflated to 2003 Euros using
      published governmental conversion tables. RESULTS: Seven published studies were
      identified, spanning the following country settings: the US, Belgium and France,
      Germany, Hungary, Italy, Spain, and the UK. In each, the same pharmacoeconomic
      model was adapted using country-specific data to project and evaluate the
      clinical and cost outcomes of the treatment arms of the Irbesartan in Diabetic
      Nephropathy Trial (IDNT) (irbesartan, amlodipine or standard blood pressure
      control). Mean time to onset of ESRD was 8.23 years for irbesartan, 6.82 years
      for amlodipine and 6.88 years for the control (values were the same for Belgium,
      France, Germany, Hungary, Italy and Spain as transition probabilities for
      progression to ESRD were all derived from the IDNT). Mean cumulative incidence of
      ESRD was 36% with irbesartan, 49% with amlodipine and 45% with control treatment.
      Treatment with irbesartan was projected to improve life expectancy compared to
      both amlodipine and control in all seven published studies. Analysis of total
      lifetime costs showed that irbesartan treatment was cost saving compared to the
      other two treatment regimens, due to the associated reduction in ESRD cases. Cost
      savings with irbesartan became evident very early; after 2-3 years of treatment
      in most settings. CONCLUSIONS: Modelling studies based on the IDNT published to
      date suggest that irbesartan treatment in patients with type 2 diabetes,
      hypertension and advanced nephropathy is both life- and cost-saving compared to
      amlodipine or control.

PMID- 15855215
TI  - Multiple hepatic masses in a 38-year-old male 10 years after renal
      transplantation.

PMID- 15855216
TI  - Beneficial effect of vitamin E supplementation on the biochemical and kinetic
      properties of Tamm-Horsfall glycoprotein in hypertensive and hyperoxaluric
      patients.
AB  - BACKGROUND: This study aimed to assess the therapeutic efficacy of oral vitamin E
      supplementation on the biochemical and kinetic properties of Tamm-Horsfall
      glycoprotein (THP) in hypertensive and hyperoxaluric patients. METHODS: Newly
      detected hypertensives (n = 200) and stone formers (n = 200) were each subdivided
      into two groups. One group (n = 100) was administered the antioxidant vitamin E
      at 400 mg/day given as an oral supplement along with standard therapeutic drugs
      for hypertension and hyperoxaluria and the patients were followed for a period of
      9 months. The other group (n = 100) did not receive vitamin E (placebo controls).
      Age and sex-matched controls (n = 100) were monitored simultaneously. THP was
      isolated from 24 h urine samples before and at the end of every third month
      during a period of 9 months from the vitamin E-treated hypertensive and
      hyperoxaluric groups. THP samples were also collected from control subjects, and
      at the end of the ninth month from placebo controls. The isolated protein was
      assessed for purity by SDS-PAGE. The purity-checked proteins were subjected to
      spectrophotometric crystallization assay, calcium oxalate (CaOx) crystal
      interaction studies, and biochemical analysis of sialic acid, thiol and carbonyl
      content. Plasma superoxide, hydroxyl radical, hydrogen peroxide and vitamin E
      levels as well as superoxide dismutase and catalase activities were also
      monitored. RESULTS: The THP from the hypertensive and hyperoxaluric subjects
      exhibited a significant promoting effect on the nucleation and aggregation phases
      and caused a concomitant increase in CaOx crystal interaction. The altered
      kinetic properties of THP in these subjects were strongly associated with
      increased carbonyl content and with decreased thiol and sialic acid contents.
      Oral administration of vitamin E to these patients caused near normalization of
      these biochemical alterations and satisfactorily restored the kinetic properties
      of THP to near normal activity. At the end of 9 months, THP isolated from placebo
      controls (hypertensive and hyperoxaluric) showed highly aggregated calcium
      oxalate monohydrate crystals as observed by light microscopy. In contrast,
      vitamin E-supplemented patients showed CaOx dihydrate crystals that were similar
      to control THP. There was an imbalance in the oxidant and antioxidant levels. For
      the oxidants, superoxide, hydrogen peroxide and hydroxyl radical levels were
      increased, and for the antioxidants, there was loss of antioxidant enzyme
      activities and a decline in plasma vitamin E level in both hypertensive and
      hyperoxaluric patients. Supplementary antioxidant (vitamin E) corrected this
      imbalance to near normal conditions. CONCLUSION: We hypothesize that the loss of
      THP inhibitory activity in the hypertensive and hyperoxaluric patients in a
      crystallizing medium is mediated primarily by oxidative damage to this protein.
      The possible occurrence of renal stones in essential hypertensive subjects, and
      the risk of recurrence in hyperoxaluric subjects, may be explained by oxidative
      damage to renal tissues that remained unchecked by standard drug therapies. The
      normalization of the kinetic properties of THP following vitamin E
      supplementation is in support of our hypothesis.

PMID- 15855217
TI  - Where do we stand with renovascular hypertension?

PMID- 15855218
TI  - Challenges in improving care for high-risk seniors in Medicare.
AB  - Despite strong interest in improving care for high-risk elders, demonstration
      projects typically show negative results. This paper examines one large
      foundation-sponsored initiative to gain insight on why success often is so
      elusive. The findings indicate that specific flaws in concept, design, and
      implementation each make it more challenging for demonstrations to achieve their
      intended goals, especially those involving cost and utilization reductions. We
      speculate that part of the reason for this is that organizational and political
      processes lead to fundamentally conservative demonstrations that assume that
      small amounts of resources directed at incremental change can be effective in
      generating substantial change in organizations and can do so rapidly.

PMID- 15855219
TI  - Radiocontrast-induced acute renal failure.
AB  - The intravascular administration of iodinated radiocontrast media can lead to
      acute renal dysfunction. Even small changes in renal function have been
      associated with increased morbidity and mortality, making the prevention of
      radiocontrast nephropathy of paramount importance. This review summarizes the
      principal risk factors for radiocontrast nephropathy and evidence-based
      preventive strategies that should be used to limit its occurrence. Risk factors
      for radiocontrast nephropathy include preexistent kidney disease, diabetes
      mellitus, dose of radiocontrast used, advanced congestive heart failure, and
      intravascular volume depletion. Proven preventive measures include volume
      expansion with intravenous saline or sodium bicarbonate and the use of low
      osmolar or iso-osmolar radiocontrast media. Studies evaluating N-acetylcysteine
      have been conflicting, with meta-analyses suggesting a small beneficial effect.
      Studies of other pharmacologic agents have not demonstrated clinical benefit.

PMID- 15855220
TI  - Lung injury and bronchopulmonary dysplasia in newborn infants.
AB  - Bronchopulmonary dysplasia is the most common morbidity among surviving premature
      infants. Injury to the developing lung is the result of the interaction between a
      susceptible host and a number of contributing factors such as mechanical
      ventilation and infection. The resulting persistent impairment of pulmonary
      function and need for ongoing therapy are the underlying characteristics of
      bronchopulmonary dysplasia. Important insights into the pathogenesis of
      bronchopulmonary dysplasia have led to numerous therapies and preventive
      approaches. Although significant progress has been made, in order to further
      affect the incidence and severity of the disease, we need to further study (a)
      the genetically determined predisposing factors, (b) the relative contribution of
      the various pathogenetic pathways, and, most important, (c) how to best translate
      the knowledge gained from these studies into effective clinical approaches.

PMID- 15855221
TI  - Use of cellular and plasma apheresis in the critically ill patient: Part II:
      Clinical indications and applications.
AB  - Apheresis is the process of separating the blood and removing or manipulating a
      cellular or plasma component for therapeutic benefit. Such procedures may be
      indicated in the critical care setting as primary or adjunctive therapy for
      certain hematologic, neurologic, renal, and autoimmune/rheumatologic disorders.
      In part I of this series, the technical aspects of apheresis were described and
      the physiologic rationale and clinical considerations were discussed. This review
      highlights the pathophysiologic basis, specific clinical indications, and
      treatment parameters for disorders that more commonly require management in the
      intensive care unit. The choice of plasma or cellular apheresis in these cases is
      guided by well-accepted, evidence-based clinical treatment guidelines. For some
      disorders, such as liver failure, severe sepsis, and multiple-organ dysfunction
      syndrome, apheresis treatment approaches remain experimental. Ongoing studies are
      investigating the potential utility of conventional plasma exchange, ex vivo
      plasma manipulation, and newer technologies for these and other disorders in
      severely ill patients.

PMID- 15855222
TI  - Outcome after tracheostomy for respiratory failure in the elderly.
AB  - The purpose of this study was to determine hospital and postdischarge survival
      and functional status at follow-up in elderly patients receiving tracheostomy for
      respiratory failure and to determine if these outcomes differed between the
      younger elderly (65-74 years) and the older elderly (> or = 75 years). This was a
      retrospective chart review with prospective administration of the SF-36 conducted
      in 228 patients aged 65 years or older who had undergone tracheostomy to
      facilitate mechanical ventilation for respiratory failure at a tertiary care,
      university-affiliated, urban medical center. Demographics, comorbidities,
      hospital survival, liberation from mechanical ventilation, long-term survival,
      and functional status were determined. Combined hospital and hospice mortality
      did not differ by age, being 34% and 26% in the 65- to 74-year and > or = 75-year
      groups, respectively (P> .05). However, older patients (> or = 75 years old) were
      more likely to be discharged still requiring mechanical ventilation (62% vs 45%,
      P< .05). Only one half of hospital survivors survived for 1 additional year.
      Those discharged ventilator-dependent were more likely to die. Of the 20
      participants in the SF-36 portion of the study, most had fair to good emotional
      and social functioning but were extremely limited physically.

PMID- 15855223
TI  - Propofol use precludes prescription of estimated nitrogen requirements.
AB  - The objective was to determine whether reducing enteral nutrition to accommodate
      1% Propofol-derived energy results in suboptimal nitrogen prescription. This was
      a prospective observational study of 85 consecutive patients requiring mechanical
      ventilation and receiving 1% Propofol. Enteral nutrition prescription often
      failed to meet nitrogen requirements (<90%, in 50.6%; <80%, in 21.1%), whereas
      fat provided 51% of total energy input, exceeding 2 g fat/kg/d in 20%. However,
      gastroparesis was common, resulting in suboptimal nutrition (median of
      requirements: energy 71%; nitrogen 57%). If energy balance had been strictly
      maintained, substituting 1% with 2% Propofol would reduce the number of patients
      failing to meet nitrogen requirements (1% vs 2%: <90%: in 58.8% vs 17.6%, P<
      .001; <80% in 35.3% vs 4.7%, P< .014). These effects are directly related to the
      amount of fat delivered with Propofol. Intensive care unit-associated
      gastroparesis commonly reduces enteral nutrition input. However, even where this
      is overcome, use of 1% Propofol frequently precludes prescription of estimated
      nitrogen requirements; either 2% Propofol or a non-Propofol alternative should be
      considered.

PMID- 15855224
TI  - Dexmedetomidine in the treatment of withdrawal syndromes in cardiothoracic
      surgery patients.
AB  - Dexmedetomidine (Precedex, Abbott Laboratories, Abbott Park, IL) is an alpha 2
      adrenergic agonist that possesses a high ratio of specificity for the alpha 2
      versus the alpha 1 receptor. It is currently approved for the provision of
      sedation during mechanical ventilation in adults. Given previous experience with
      clonidine for the treatment of substance withdrawal and the preliminary anecdotal
      experience with dexmedetomidine, it appears that dexmedetomidine may be a useful
      agent for treatment of substance withdrawal in the intensive care setting. The
      authors present their experience with the use of dexmedetomidine to control
      withdrawal behavior in 3 patients following cardiothoracic surgery. Previous
      reports regarding the use of dexmedetomidine to treat withdrawal and its
      potential application in this clinical arena are reviewed.

PMID- 15855225
TI  - Are all high-grade breast cancers with no steroid receptor hormone expression
      alike? The special case of the medullary phenotype.
AB  - BACKGROUND: Medullary carcinoma (MC) of the breast is associated with favorable
      prognosis compared with other histological types, despite high nuclear grade,
      fast proliferation and lack of steroid hormone receptor expression. We
      retrospectively evaluated the clinical relevance of selected immunohistochemical
      features of tumors in three cohorts of patients with typical medullary (MC),
      'atypical' medullary (AMC) or ductal (DC) breast carcinoma. PATIENTS AND METHODS:
      Evaluation was performed on node-negative tumor specimens from 40 patients who
      had either MC (12 patients), AMC (nine patients) or DC (19 patients), treated in
      a single institution. All had no hormonal receptor, Ki-67 > or =30%, G3,
      expansive pattern of growth and peritumoral lymphocytic infiltration. In
      addition, p27, p21 and HER2/neu overexpression, p53, cyclin E and E-cadherin
      expression, presence of apoptotic cells, stromal tenascin (TN), and type of
      immune cell infiltration (CD3- and CD68-positive cells) were assessed. RESULTS:
      No difference in expression of HER2/neu, p21, p27, p53, number of apoptotic cells
      and CD68-positive cells was detected. Lower levels of stromal TN expression were
      found in MC compared with DC (P=0.0007), but differences between MC and AMC were
      not significant (P=0.27). A higher proportion of intratumoral CD3-positive cells
      was seen in MC than in AMC (P=0.046). No differences were seen between MC and DC
      (P=0.73). With a median follow-up of 67 months, three patients with DC had
      relapsed in distant sites, while one patient with AMC had a second primary. Two
      patients with MC had reappearance of DC in the breast. CONCLUSIONS: The three
      distinct disease types, selected by having similar high proliferation, had
      similar expression of cell cycle regulators. The lower expression of TN and
      massive infiltration of T lymphocytes might both indicate a special interaction
      between tumor cells and microenvironment, important features for conferring
      improved prognosis through negligible invasive and metastatic potential to MC. In
      our series, however, patients with a previous MC are not free from the risk of
      developing a subsequent DC. Finally, defining AMC as a distinct entity from DC is
      not justified.

PMID- 15855226
TI  - Irinotecan or oxaliplatin combined with leucovorin and 5-fluorouracil as first
      line treatment in advanced colorectal cancer: a multicenter, randomized, phase II
      study.
AB  - BACKGROUND: Irinotecan (IRI) and oxaliplatin (OXA) are effective in the treatment
      of colorectal cancer. Previously untreated patients with advanced colorectal
      carcinoma (CRC) were randomly assigned to receive IRI plus leucovorin (LV)/5
      fluorouracil (5-FU), or OXA plus LV/5-FU in order to compare the response rates,
      time-to-tumor progression, overall survival rates, and toxicity profiles of these
      two agents. MATERIALS AND METHODS: From January 1999 to February 2002, 295
      patients were randomized to receive either IRI/LV/5-FU or OXA/LV/5-FU. The
      treatment schedules consisted of weekly IRI 70 mg/m(2) or OXA 45 mg/m(2) plus LV
      200 mg/m(2) followed immediately by intravenous bolus 5-FU 450 mg/m(2) for 6
      weeks, followed by a 2-week rest period. Treatment was continued for up to four
      cycles or until disease progression, unacceptable toxicity or patient refusal.
      RESULTS: There were no significant differences between the study arms in the
      overall response rate (33% with IRI/LV/5-FU versus 32% with OXA/LV/5-FU based on
      responses demonstrated on a single evaluation; 23% with IRI/LV/5-FU versus 22.3%
      with OXA/LV/5-FU based on responses confirmed according to WHO criteria) median
      time to progression (8.9 versus 7.6 months), and median overall survival (17.6
      versus 17.4 months). Toxicity profiles (grades 3 and 4) were similar in the IRI
      and OXA arms (diarrhea 12.3% and 9.8%, neutropenia 8.2% and 4.9%, and febrile
      neutropenia 1.4% and 1.4%, respectively), with the exception of grade 3 sensory
      neuropathy, which almost exclusively occurred in the OXA arm (0% versus 5.6%;
      P=0.003, Fisher's exact test). CONCLUSION: The IRI/LV/5-FU and OXA/LV/5-FU
      regimens demonstrated equally substantial efficacies and manageable toxicity
      profiles in the first-line treatment of patients with advanced CRC. However,
      IRI/LV/5-FU may be the preferable regimen to avoid significant neurotoxicity
      associated with OXA-LV/5-FU.

PMID- 15855227
TI  - Protection against endotoxemia-induced contractile dysfunction in mice with
      cardiac-specific expression of slow skeletal troponin I.
AB  - Gram negative endotoxemia is associated with an intrinsic impairment of
      cardiomyocyte contraction, in part due to a reduction in myofilament Ca2+
      responsiveness. Endotoxemic rat hearts show increased cardiac troponin I (cTnI)
      phosphorylation at serines 23 and 24, residues required for the protein kinase A
      (PKA)-dependent reduction of myofilament Ca2+ sensitivity after beta-adrenoceptor
      stimulation. To investigate the functional significance of increased TnI
      phosphorylation in endotoxemia, we studied the contractile effects of systemic
      bacterial lipopolysaccharide (LPS) treatment in transgenic mice (TG) with cardiac
      specific replacement of cTnI by slow skeletal TnI (ssTnI, which lacks the PKA
      phosphorylation sites) and matched nontransgenic littermates (NTG) on a CD1
      background. In wild-type CD1 mice treated with LPS (6 mg/kg ip), after 16-18 h
      there was a significant reduction in the maximum rates of left ventricular
      pressure development and pressure decline in isolated Langendorff-perfused hearts
      compared with saline-treated controls and a decrease in isolated myocyte unloaded
      sarcomere shortening from 6.1 +/- 0.2 to 3.9 +/- 0.2% (1 Hz, 32 degrees C,
      P<0.05). Similarly, in NTG myocytes, endotoxemia reduced myocyte shortening by
      42% from 6.7 +/- 0.2 to 3.9 +/- 0.1% (P<0.05) with no change in intracellular
      Ca2+ transients. However, in the TG group, LPS reduced myocyte shortening by only
      13% from 7.5 +/- 0.2 to 6.5 +/- 0.2% (P<0.05). LPS treatment significantly
      reduced the positive inotropic effect of isoproterenol in NTG myocytes but not in
      TG myocytes, even though isoproterenol-induced increases in Ca2+ transient
      amplitude were similar in both groups. Only LPS-treated NTG hearts showed a
      significant increase in cTnI phosphorylation. Investigation of the sarcomere
      shortening-Ca2+ relationship in Triton-skinned cardiomyocytes revealed a
      significant reduction in myofilament Ca2+ sensitivity after LPS treatment in NTG
      myocytes, an effect that was substantially attenuated in TG myocytes. In
      conclusion, the replacement of cTnI with ssTnI in the heart provides significant
      protection against endotoxemia-induced cardiac contractile dysfunction, most
      probably by preserving myofilament Ca2+ responsiveness due to prevention of
      phosphorylation of TnI at PKA-sensitive sites.

PMID- 15855228
TI  - Chronic umbilical cord compression results in accelerated maturation of lung and
      brown adipose tissue in the sheep fetus during late gestation.
AB  - Umbilical cord compression (UCC) sufficient to reduce umbilical blood flow by 30%
      for 3 days, results in increased fetal plasma cortisol and catecholamines that
      are likely to promote maturation of the fetal lung and brown adipose tissue
      (BAT). We determined the effect of UCC on the abundance of uncoupling protein
      (UCP)1 (BAT only) and -2, glucocorticoid receptor (GR), and 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD)1 and -2 mRNA, and mitochondrial protein voltage
      dependent anion channel (VDAC) and cytochrome c in these tissues. At 118 +/- 2
      days of gestation (dGA; term approximately 145 days), 14 fetuses were chronically
      instrumented. Eight fetuses were then subjected to 3 days of UCC from 125 dGA,
      and the remaining fetuses were sham operated. All fetuses were then exposed to
      two 1-h episodes of hypoxemia at 130 +/- 1 and 134 +/- 1 dGA before tissue
      sampling at 137 +/- 2 dGA. In both tissues, UCC upregulated UCP2 and GR mRNA,
      plus VDAC and cytochrome c mitochondrial proteins. In lung, UCC increased 11beta
      HSD1 mRNA but decreased 11beta-HSD2 mRNA abundance, a pattern reversed for BAT.
      UCC increased UCP1 mRNA and its translated protein in BAT. UCP2, GR, 11beta-HSD1
      and -2 mRNA, plus VDAC and cytochrome c protein abundance were all significantly
      correlated with fetal plasma cortisol and catecholamine levels, but not thyroid
      hormone concentrations, in the lung and BAT of UCC fetuses. In conclusion,
      chronic UCC results in precocious maturation of the fetal lung and BAT
      mitochondria, an adaptation largely mediated by the surge in fetal plasma
      cortisol and catecholamines that accompanies UCC.

PMID- 15855229
TI  - Differential regulation of fatty acid elongation enzymes in brown adipocytes
      implies a unique role for Elovl3 during increased fatty acid oxidation.
AB  - The expression of the Elovl3 gene, which belongs to the Elovl gene family coding
      for microsomal enzymes involved in very long-chain fatty acid (VLCFA) elongation,
      is dramatically increased in mouse brown adipose tissue upon cold stimulation. In
      the present study, we show that the cold-induced Elovl3 expression is under the
      control of peroxisome proliferator-activated receptor-alpha (PPARalpha) and that
      this regulation is part of a fundamental divergence in the regulation of
      expression for the different members of the Elovl gene family. In cultured brown
      adipocytes, a mixture of norepinephrine, dexamethasone, and the PPARalpha ligand
      Wy-14643, which rendered the adipocytes a high oxidative state, was required for
      substantial induction of Elovl3 expression, whereas the same treatment suppressed
      Elovl1 mRNA levels. The nuclear liver X receptor (LXR) has been implicated in the
      control of fatty acid synthesis and subsequent lipogenic processes in several
      tissues. This regulation is also exerted in part by sterol regulatory element
      binding protein (SREBP-1), which is a target gene of LXR. We found that
      stimulation of Elovl3 expression was independent of LXR and SREBP-1 activation.
      In addition, exposure to the LXR agonist TO-901317 increased nuclear abundance of
      LXR and mature SREBP-1 as well as expression of the elongases Lce and Elovl1 in a
      lipogenic fashion but repressed Elovl3 expression. A functional consequence of
      this was seen on the level of esterified saturated fatty acids, such as C22:0,
      which was coupled to Elovl3 expression. These data demonstrate differential
      transcriptional regulation and concomitantly different functional roles for fatty
      acid elongases in lipid metabolism of brown adipocytes, which reflects the
      metabolic status of the cells.

PMID- 15855230
TI  - Functional contribution of Pds5 to cohesin-mediated cohesion in human cells and
      Xenopus egg extracts.
AB  - Sister chromatid cohesion is essential for proper segregation of the genome in
      mitosis and meiosis. Central to this process is cohesin, a multi-protein complex
      conserved from yeast to human. Previous genetic studies in fungi have identified
      Pds5/BimD/Spo76 as an additional factor implicated in cohesion. Here we describe
      the biochemical and functional characterization of two Pds5-like proteins, Pds5A
      and Pds5B, from vertebrate cells. In HeLa cells, Pds5 proteins physically
      interact with cohesin and associate with chromatin in a cohesin-dependent manner.
      Depletion of the cohesin subunit Scc1 by RNA interference leads to the assembly
      of chromosomes with severe cohesion defects. A similar yet milder set of defects
      is observed in cells with reduced levels of Pds5A or Pds5B. In Xenopus egg
      extracts, mitotic chromosomes assembled in the absence of Pds5A and Pds5B display
      no discernible defects in arm cohesion, but centromeric cohesion is apparently
      loosened. Unexpectedly, these chromosomes retain an unusually high level of
      cohesin. Thus, Pds5 proteins seem to affect the stable maintenance of cohesin
      mediated cohesion and its efficient dissolution during mitosis. We propose that
      Pds5 proteins play both positive and negative roles in sister chromatid cohesion,
      possibly by directly modulating the dynamic interaction of cohesin with
      chromatin. This idea would explain why cells lacking Pds5 function display rather
      complex and diverse phenotypes in different organisms.

PMID- 15855232
TI  - Targeting of voltage-gated potassium channel isoforms to distinct cell surface
      microdomains.
AB  - Voltage-gated potassium (Kv) channels regulate action potential duration in nerve
      and muscle; therefore changes in the number and location of surface channels can
      profoundly influence electrical excitability. To investigate trafficking of
      Kv2.1, 1.4 and 1.3 within the plasma membrane, we combined the expression of
      fluorescent protein-tagged Kv channels with live cell confocal imaging. Kv2.1
      exhibited a clustered distribution in HEK cells similar to that seen in
      hippocampal neurons, whereas Kv1.4 and Kv1.3 were evenly distributed over the
      plasma membrane. Using FRAP, surface Kv2.1 displayed limited mobility;
      approximately 40% of the fluorescence recovered within 20 minutes of photobleach
      (M(f)=0.41+/-0.04). Recovery occurred not by diffusion from adjacent membrane but
      probably by transport of nascent channel from within the cell. By contrast, the
      Kv1 family members Kv1.4 and Kv1.3 were highly mobile, both showing approximately
      80% recovery (Kv 1.4 M(f)=0.78+/-0.07; Kv1.3 M(f)=0.78+/-0.04; without correction
      for photobleach); unlike Kv2.1, recovery was consistent with diffusion of channel
      from membrane adjacent to the bleach region. Studies using PA-GFP-tagged channels
      were consistent with the FRAP results. Following photoactivation of a small
      region of plasma membrane PA-GFP-Kv2.1 remained restricted to the photoactivation
      ROI, while PA-GFP-Kv1.4 rapidly diffused throughout the cell surface.
      Additionally, PA-GFP-Kv2.1 moved into regions of the cell membrane not adjacent
      to the original photoactivation ROI. Sucrose density gradient analysis indicated
      that half of Kv2.1 is part of a large, macromolecular complex while Kv1.4
      sediments as predicted for the tetrameric channel complex. Disruption of membrane
      cholesterol by cyclodextrin minimally altered Kv2.1 mobility (M(f)=0.32+/-0.03),
      but significantly increased surface cluster size by at least fourfold. By
      comparison, the mobility of Kv1.4 decreased following cholesterol depletion with
      no change in surface distribution. The mobility of Kv1.3 was slightly increased
      following cyclodextrin treatment. These results indicate that (1) Kv2.1, Kv1.4
      and Kv1.3 exist in distinct compartments that exhibit different trafficking
      properties, (2) membrane cholesterol levels differentially modulate the
      trafficking and localization of Kv channels and (3) Kv2.1 expressed in HEK cells
      exhibits a surface distribution similar to that seen in native cells.

PMID- 15855233
TI  - CD95 capping is ROCK-dependent and dispensable for apoptosis.
AB  - Upon engagement, the CD95 receptor is rapidly clustered into cellular 'caps'.
      This receptor capping is one of the first events to take place following
      activation and it has been proposed to be important for the initiation of
      apoptotic signaling. As the biological roles of CD95 capping are still elusive,
      we explored in detail the role of capping in induction of apoptosis in
      lymphocytes. CD95 capping was shown to be uncoupled from apoptosis, as apoptosis
      could occur in the absence of CD95 capping and, vice versa, capping could occur
      without inducing apoptosis. CD95 capping occurred concomitantly with
      reorganization of the actin cytoskeleton and aggregation of lipid rafts. While
      inhibition of actin polymerization and caspase-8 activity had cell type-specific
      effects on capping in type I and type II cells, the rapid CD95-mediated cellular
      polarization, as visualized by the orchestrated reorganization of CD95, F-actin
      and lipid rafts, was shown to be dependent on signaling by Rho kinase (ROCK) in
      both cell types, however, by distinct activation mechanisms in the respective
      cell type. CD95 activated RhoA exclusively in the type II cell, whereas ROCK
      activation was caspase-dependent in the type I cell. Taken together, our results
      imply that CD95 capping and the subsequent cellular polarization is a ROCK
      signaling-regulated process that does not correlate with the induction of
      apoptosis, but is more likely to be involved in the emerging non-apoptotic
      functions of CD95.

PMID- 15855234
TI  - Computer-assisted analysis of filopod formation and the role of myosin II heavy
      chain phosphorylation in Dictyostelium.
AB  - To investigate the role played by filopodia in the motility and chemotaxis of
      amoeboid cells, a computer-assisted 3D reconstruction and motion analysis system,
      DIAS 4.0, has been developed. Reconstruction at short time intervals of
      Dictyostelium amoebae migrating in buffer or in response to chemotactic signals,
      revealed that the great majority of filopodia form on pseudopodia, not on the
      cell body; that filopodia on the cell body originate primarily on pseudopodia and
      relocate; and that filopodia on the uropod are longer and more stable than those
      located on other portions of the cell. When adjusting direction through lateral
      pseudopod formation in a spatial gradient of chemoattractant, the temporal and
      spatial dynamics of lateral pseudopodia suggest that filopodia may be involved in
      stabilizing pseudopodia on the substratum while the decision is being made by a
      cell either to turn into a pseudopodium formed in the correct direction (up the
      gradient) or to retract a pseudopodium formed in the wrong direction (down the
      gradient). Experiments in which amoebae were treated with high concentrations of
      chemoattractant further revealed that receptor occupancy plays a role both in
      filopod formation and retraction. As phosphorylation-dephosphorylation of myosin
      II heavy chain (MHC) plays a role in lateral pseudopod formation, turning and
      chemotaxis, the temporal and spatial dynamics of filopod formation were analyzed
      in MHC phosphorylation mutants. These studies revealed that MHC phosphorylation
      dephosphorylation plays a role in the regulation of filopod formation during cell
      migration in buffer and during chemotaxis. The computer-assisted technology
      described here for reconstructing filopodia at short time intervals in living
      cells, therefore provides a new tool for investigating the role filopodia play in
      the motility and chemotaxis of amoeboid cells.

PMID- 15855235
TI  - Identification of an upstream regulatory pathway controlling actin-mediated
      apoptosis in yeast.
AB  - The build up of reactive oxygen species (ROS) is known to contribute to a
      reduction in the lifespan of a cell and to their degeneration in diseases such as
      Alzheimer's and tissue ischaemia. It is therefore important to elucidate pathways
      that regulate cellular oxidative stress. We have previously shown that actin
      dynamics can affect the oxidative-stress burden on a yeast cell and thereby its
      potential lifespan. To elucidate further the connection between actin dynamics
      and oxidative stress, we sought to identify regulators of this process. The actin
      regulatory proteins Sla1p and End3p are important in maintaining a rapid turnover
      of F-actin in cortical patches. We show that cells expressing a mutated form of
      Sla1p or lacking End3p display markers of apoptosis such as depolarized
      mitochondrial membranes and elevated levels of reactive oxygen species.
      Overexpression of the ubiquitin ligase RSP5 can alleviate the oxidative-stress
      phenotype observed in cells lacking End3p by targeting Sla1p to the cortex and
      restoring actin remodelling capability. We also demonstrate that overexpression
      of PDE2, a negative regulator of the Ras/cAMP pathway rescues actin dynamics,
      reduces oxidative stress sensitivity and restores viability in deltaend3 cells.
      Our data suggest, for the first time, that a physiological link exists between
      actin regulation and cAMP signalling that regulates apoptosis in yeast.

PMID- 15855236
TI  - Breast cancer cells induce stromal fibroblasts to express MMP-9 via secretion of
      TNF-alpha and TGF-beta.
AB  - We used 2D-cocultures employing fibroblasts of different genetic backgrounds and
      MCF10A-derived human breast epithelial cells of increasingly malignant potential
      to investigate tumor-stroma interactions in breast cancer and to identify
      possible signaling pathways involved. Tumor cells induced expression of matrix
      metalloproteinase 9 (MMP-9) in fibroblasts in a pattern dependent on the degree
      of their malignancy. In-situ zymography localized the main gelatinolytic activity
      around stromal cells in cocultures and xenografted tumors. Use of Smad3 knockout
      fibroblasts, small molecule inhibitors, and neutralizing antibodies showed that
      MMP-9 expression was induced by tumor cell-derived TNF-alpha and TGF-beta,
      dependent on Smad-, Ras-, and PI3-kinase-signaling, and likewise modulated by
      subsequent HGF- and EGF-signaling. Together, our results indicate that MMP-9
      levels in tumor fibroblasts are regulated by a complex tumor-stroma cross-talk,
      involving multiple ligands and cellular signaling pathways.

PMID- 15855237
TI  - ZO-1 alters the plasma membrane localization and function of Cx43 in osteoblastic
      cells.
AB  - ZO-1 is the major connexin-interacting protein in ROS 17/2.8 (ROS) osteoblastic
      cells. We examined the role of ZO-1 in Cx43-mediated gap junction formation and
      function in ROS cells that expressed the connexin-interacting fragment of ZO-1
      (ROS/ZO-1dn) cells. Expression of this ZO-1(7-444) fusion protein in ROS cells
      disrupted the Cx43/ZO-1 interaction and decreased dye transfer by 85%, although
      Cx43 was retained on the plasma membrane as assessed by surface biotinylation.
      Fractionation of lysates derived from ROS/ZO-1dn cells on a 5-30% sucrose
      flotation gradient showed that 40% of the Cx43 floated into these sucrose
      gradients, whereas none of the Cx43 in ROS cell lysates entered the gradients,
      suggesting that more Cx43 is associated with lipid rafts in the transfected ROS
      cells than in lysates derived from untransfected ROS cells. In contrast to the
      ROS/ZO-1dn cells, ROS cells that over-expressed ZO-1 protein (ROS/ZO-1myc cells)
      exhibited increased gap junctional permeability and appositional membrane
      staining for Cx43. These data demonstrate that ZO-1 regulates Cx43-mediated gap
      junctional communication in osteoblastic cells and alters the membrane
      localization of Cx43. They suggest that ZO-1-mediated delivery of Cx43 from a
      lipid raft domain to gap junctional plaques may be an important regulatory step
      in gap junction formation.

PMID- 15855238
TI  - Cellular invasion by Staphylococcus aureus reveals a functional link between
      focal adhesion kinase and cortactin in integrin-mediated internalisation.
AB  - Nosocomial infections by Staphylococcus aureus, a Gram-positive pathogen
      colonising human skin and mucosal surfaces, are an increasing health care
      problem. Clinical isolates almost invariably express fibronectin-binding proteins
      that, by indirectly linking the bacteria with host integrin alpha5beta1, can
      promote uptake of the microorganisms by eukaryotic cells. Integrin engagement by
      pathogenic fibronectin-binding S. aureus, but not by non-pathogenic S. carnosus,
      triggered the recruitment of focal contact-associated proteins vinculin, tensin,
      zyxin and FAK to the sites of bacterial attachment. Moreover, dominant-negative
      versions of FAK-blocked integrin-mediated internalisation and FAK-deficient cells
      were severely impaired in their ability to internalise S. aureus. Pathogen
      binding induced tyrosine phosphorylation of several host proteins associated with
      bacterial attachment sites, including FAK and the Src substrate cortactin. In FAK
      deficient cells, local recruitment of cortactin still occurred, whereas the
      integrin- and Src-dependent tyrosine phosphorylation of cortactin was abolished.
      As siRNA-mediated gene silencing of cortactin or mutation of critical amino acid
      residues within cortactin interfered with uptake of S. aureus, our results reveal
      a novel functional connection between integrin engagement, FAK activation and Src
      mediated cortactin phosphorylation. Cooperation between FAK, Src and cortactin in
      integrin-mediated internalisation of bacteria also suggests a molecular scenario
      of how engagement of integrins could be coupled to membrane endocytosis.

PMID- 15855239
TI  - The membrane-bound histidine acid phosphatase TbMBAP1 is essential for
      endocytosis and membrane recycling in Trypanosoma brucei.
AB  - In the parasitic protozoan Trypanosoma brucei, endocytosis and exocytosis occur
      exclusively at an invagination of the plasma membrane around the base of the
      flagellum, called the flagellar pocket, which actively communicates by vesicular
      membrane flow with cisternal/tubulovesicular endosomes. The division of the cell
      surface into three morphologically distinct sub-domains and the rapid plasma
      membrane turnover establishes T. brucei as an interesting model for
      investigations on the sorting and recycling of membrane proteins. In this study
      we show that the type I membrane protein TbMBAP1, an L-(+)-tartrate-sensitive
      acid phosphatase, is present in all endosomal membranes but is virtually absent
      from the lysosome membrane (where this type of protein is mainly found in other
      organisms) and is not detectable at the cell surface. The endosomal localization
      of TbMBAP1 is a function of protein abundance. Moderate overexpression (three- to
      fourfold) leads to an increased appearance within the flagellar pocket membrane.
      At higher levels the protein is found in the flagellum, and routing to the
      pellicular plasma membrane is observed at levels 10- to 25-fold above that of
      wild type. In other organisms L-(+)-tartrate-sensitive acid phosphatases appear
      to be dispensable but TbMBAP1 is essential, as shown by RNA interference, which
      causes growth arrest followed by cell death. Comparison of the phenotype of
      TbMBAP1-depleted cells with that of cells in which endocytosis or exocytosis has
      been specifically inhibited by RNAi against clathrin of RAB11, reveals that
      TbMBAP1 is essential for both incoming and recycling membrane traffic. During
      differentiation of the organism from bloodstream to insect stage, TbMBAP1 is down
      regulated and differentially modified in parallel with a 10-fold decrease in the
      rate of endocytosis.

PMID- 15855240
TI  - Miller fisher variant of guillain-barre syndrome requiring a cardiac pacemaker in
      a patient on tacrolimus after liver transplantation.
AB  - OBJECTIVE: To report a case of Miller Fisher syndrome (MFS), a variant of
      Guillain-Barre syndrome (GBS) necessitating the placement of a permanent cardiac
      pacemaker in a patient on tacrolimus after a cadaveric orthotopic liver
      transplantation. CASE SUMMARY: A 46-year-old African American male, who had been
      receiving tacrolimus 4 mg/day orally for the preceding 6 months, developed a
      Miller Fisher variant of GBS (severe ataxia, ophthalmoplegia, areflexia). He
      developed symptomatic sinus pauses requiring a cardiac pacemaker. He improved
      substantially after cessation of tacrolimus and initiation of intravenous
      immunoglobulin therapy. The patient was not rechallenged with tacrolimus due to
      the clinical/ethical gravity of this probable adverse effect. DISCUSSION:
      Although different types of neuropathies have been reported with the use of
      tacrolimus, to the best of our knowledge, this is the first case report of a
      Miller Fisher variant of GBS severe enough to cause dysautonomia requiring a
      cardiac pacemaker associated with the use of this drug. Causality assessment
      using the Naranjo probability scale revealed the adverse drug event was probable.
      CONCLUSIONS: Tacrolimus was probably associated with a Miller Fisher variant of
      GBS necessitating the placement of a permanent cardiac pacemaker in this patient.
      MFS needs to be considered a potentially life-threatening adverse effect of
      tacrolimus therapy.

PMID- 15855241
TI  - Glucosamine long-term treatment and the progression of knee osteoarthritis:
      systematic review of randomized controlled trials.
AB  - OBJECTIVE: To investigate the structural and symptomatic efficacy and safety of
      glucosamine in knee osteoarthritis (OA). DATA SOURCES: Clinical trials of
      glucosamine were identified through electronic searches (MEDLINE, EMBASE, BIOSIS,
      EMB review, the Cochrane Library) using the key words glucosamine,
      osteoarthritis, degenerative joint disease, degenerative arthritis,
      osteoarthrosis, gonarthrosis, knee, disease progression, and clinical trial. The
      bibliographic databases were searched from their respective inception dates to
      August 2004. We also hand-searched reference lists of relevant articles. STUDY
      SELECTION AND DATA EXTRACTION: Studies were included if they were double-blind,
      randomized, controlled trials that evaluated oral glucosamine long-term treatment
      in knee OA; lasting at least one year; and reporting as outcome measures the
      symptom severity and disease progression as assessed by joint space narrowing.
      Two authors interpreted data independently. Disagreements were resolved through
      discussion. DATA SYNTHESIS: Glucosamine sulfate was more effective than placebo
      in delaying structural progression in knee OA. The risk of disease progression
      was reduced by 54% (pooled RR 0.46; 95% CI 0.28 to 0.73; p = 0.0011). The number
      needed-to-treat was 9 (95% CI 6 to 20). The pooled effect sizes for pain
      reduction and improvement in physical function were 0.41 (95% CI 0.21 to 0.60; p
      < 0.0001) and 0.46 (95% CI 0.27 to 0.66; p < 0.0001), respectively, in favor of
      glucosamine sulfate. Glucosamine sulfate caused no more adverse effects than
      placebo. CONCLUSIONS: The available evidence suggests that glucosamine sulfate
      may be effective and safe in delaying the progression and improving the symptoms
      of knee OA. Due to the sparse data on structural efficacy and safety, further
      studies are warranted.

PMID- 15855242
TI  - The influence of ethnicity on warfarin dosage requirement.
AB  - BACKGROUND: The optimal dose of warfarin varies among individuals, and the
      prediction of a maintenance dose is difficult. Ethnicity has been reported to
      influence warfarin dosing. OBJECTIVE: To quantitate the influence of ethnicity on
      warfarin dose requirement. METHODS: We conducted a retrospective cohort study at
      a university anticoagulation clinic to evaluate the influence of ethnicity on
      warfarin dose. Inclusion criteria included age > or = 18 years, target
      international normalized ratio (INR) 2-3, and warfarin management within the
      clinic for > or = 3 months with a minimum of 5 clinic visits. We collected
      clinical and demographic data including age, gender, weight, ethnicity, disease
      states, concomitant medications, indication, weekly warfarin dosage, and INR. To
      assess potential confounders, multivariate, repeated-measures regression analysis
      was used to identify and adjust for variables that may influence the maintenance
      dose of warfarin. RESULTS: Of the 345 patients who met the inclusion criteria,
      27% were Asian American, 6% Hispanic, 54% white, and 14% African American. The
      adjusted mean (95% CI) weekly warfarin doses for patients with an INR goal of 2
      to 3 were Asian Americans 24 mg (21 to 27), Hispanics 31 mg (25 to 37), whites 36
      mg (34 to 39), and African Americans 43 mg (39 to 47) (p < 0.001). Additional
      factors found to influence warfarin dose requirement included age, weight,
      concomitant use of amiodarone, and diagnosis of venous thromboembolism.
      CONCLUSIONS: Warfarin dose requirements vary across ethnic groups even when
      adjusted for confounding factors, suggesting that genetic variation contributes
      to interpatient variability.

PMID- 15855243
TI  - Efficacy of sucrose to reduce pain in premature infants during eye examinations
      for retinopathy of prematurity.
AB  - BACKGROUND: Eye examinations for retinopathy of prematurity (ROP) are painful to
      the neonate. The use of topical anesthetic for eye examinations to evaluate ROP
      is routine in our neonatal intensive care unit (NICU), but does not completely
      suppress painful responses. Sweet solutions have been shown to reduce procedural
      pain in newborns. OBJECTIVE: To examine whether the addition of sucrose 24% to
      topical anesthetic improves procedural pain control during the ROP eye
      examination. METHODS: Neonates born at < or = 30 weeks' gestation were included
      in this placebo-controlled, double-blind, crossover study. Patients were randomly
      assigned to receive treatment with either proparacaine HCl ophthalmic solution
      0.5% plus 2 mL of sucrose 24% or proparacaine HCl ophthalmic solution 0.5% plus 2
      mL of sterile water (placebo) prior to an eye examination. In a subsequent eye
      examination, each patient received the alternate treatment. Oral sucrose and
      sterile water were prepared in the pharmacy in identical syringes, and
      physicians, nurses, and pharmacists in the NICU were blinded to the treatment
      given. Pain was measured using the Premature Infant Pain Profile (PIPP) scoring
      system, which measures both physical and physiologic measures of pain, and the
      scores were simultaneously assessed by 2 study nurses. PIPP scores were recorded
      1 and 5 minutes before and after the eye examination and during initial placement
      of the eye speculum. The same ophthalmologist performed all eye examinations.
      Several different definitions of a pain response were investigated. RESULTS:
      Twenty-three infants were studied, with 12 receiving sucrose and 11 receiving
      placebo as the first treatment. For 3 of the 5 definitions of pain response,
      patients experienced significantly less pain at speculum insertion with sucrose
      than with placebo. After the ROP examination, pain responses were similar with
      either sucrose or placebo. CONCLUSIONS: Oral sucrose may reduce the immediate
      pain response in premature infants undergoing eye examination for ROP.

PMID- 15855244
TI  - Potential elevation of tacrolimus trough concentrations with concomitant
      metronidazole therapy.
AB  - OBJECTIVE: To report the occurrence of a potential tacrolimus elevation in a
      renal transplant recipient after adding metronidazole to the medication regimen.
      CASE SUMMARY: A 24-year-old white man status post living-related renal transplant
      who had been stabilized on tacrolimus 4 mg twice daily (trough concentrations 7
      10 ng/mL) for 2 months and prednisone 20 mg daily presented to the clinic with
      severe diarrhea. Stool cultures were positive for Clostridium difficile, and
      therapy with metronidazole 500 mg 4 times daily was initiated. Between days 4 and
      14 of metronidazole therapy, the patient's tacrolimus trough concentration and
      serum creatinine level increased to maximum levels of 26.3 ng/mL and 3.3 mg/dL
      (baseline 1.6-1.8 mg/dL), respectively. Tacrolimus was withheld for one dose and
      then decreased to 1 mg twice daily. Two days after metronidazole discontinuation,
      tacrolimus trough concentrations dropped to 9.4 ng/mL and serum creatinine to 2.3
      mg/dL, warranting a tacrolimus dose increase to 3 mg daily. DISCUSSION: As of
      April 15, 2005, one other case has been reported documenting an elevation in
      tacrolimus concentrations with the addition of metronidazole. The possible
      mechanism may be related to metronidazole's weak inhibition of CYP3A4 and,
      possibly, P-glycoprotein. According to the Naranjo probability scale,
      metronidazole was the probable cause of this adverse reaction. CONCLUSIONS:
      Coadministration of tacrolimus with metronidazole may result in elevated
      tacrolimus concentrations, possibly leading to tacrolimus toxicity. Practitioners
      should be aware of this potential interaction and closely monitor tacrolimus
      concentrations and renal function.

PMID- 15855245
TI  - Anticoagulation monitoring part 1: warfarin and parenteral direct thrombin
      inhibitors.
AB  - OBJECTIVE: To review the availability, mechanisms, limitations, and clinical
      application of point-of-care (POC) devices used in the management of warfarin and
      parenteral direct thrombin inhibitors. DATA SOURCES: Scientific articles were
      identified through a MEDLINE search (1966-August 2004), manufacturer Web sites,
      additional references listed in articles and Web sites, and abstracts from
      scientific meetings. STUDY SELECTION AND DATA EXTRACTION: English-language
      literature from clinical trials was reviewed to evaluate the accuracy,
      reliability, and clinical application of POC monitoring devices. DATA SYNTHESIS:
      The prothrombin time expressed as the international normalized ratio (PT-INR) is
      a well-established test for monitoring warfarin anticoagulation. Multiple devices
      are available for POC testing. Because there is no universally accepted standard,
      the performance of each device is typically tested against a standard test
      performed in a reference laboratory. Performance of currently available devices,
      as measured by correlations to a standard reference laboratory PT-INR, may be
      considered very good and acceptable for use in patient care. Utilization of
      patient self-testing and patient self-monitoring of warfarin anticoagulation
      using POC devices is increasing. Parenteral direct thrombin inhibitors are
      typically monitored using a standard laboratory activated partial thromboplastin
      time. Some research has shown that POC monitoring of direct thrombin inhibitors
      using the ecarin clotting time is helpful for patients undergoing cardiopulmonary
      bypass surgery, although that test is not readily available. CONCLUSIONS: POC
      testing for anticoagulation therapy has been available for >20 years. Multiple
      POC devices are available to monitor warfarin. There is some variability in
      results between devices and between reagents used in the same device. Despite
      these limitations, POC monitoring of warfarin via the PT-INR is an integral part
      of clinical practice. Additional research evaluating POC monitoring of direct
      thrombin inhibitors is necessary.

PMID- 15855246
TI  - Dynamite extended: two new services to simplify protein dynamic analysis.
AB  - We describe two additional services now available as part of the previously
      described Dynamite protein dynamics web service. Dynatraj provides principle
      component analysis and visualization of modes of motion for a user's own ensemble
      of protein structures, e.g. from Molecular Dynamics, NMR or experimental
      ensembles. Dynapocket predicts probable configurations of a protein pocket from a
      single known structure. Both have been provided in response to requests from
      users for additional functionality from the Dynamite server. Like Dynamite, both
      are available free of charge to all users.

PMID- 15855247
TI  - jPHYDIT: a JAVA-based integrated environment for molecular phylogeny of ribosomal
      RNA sequences.
AB  - jPHYDIT is a Java application designed to furnish a visual and integrated
      environment for molecular phylogeny. The program can be used to visualize intra
      strand base-pairing information in secondary and tertiary structures of ribosomal
      RNA (rRNA) sequences. A function for the semi-automated alignment was included to
      facilitate handling of the database containing a large number of multiple-aligned
      rRNA sequences. Integration of nucleotide sequence editing, pairwise alignment,
      multiple alignment and phylogenetic treeing functions provide an easy and
      efficient way of analyzing rRNA sequences for molecular evolution, systematics,
      epidemiology and ecology.

PMID- 15855248
TI  - TFBScluster: a resource for the characterization of transcriptional regulatory
      networks.
AB  - SUMMARY: One major challenge of the post-sequencing era of the human genome
      project will be the functional annotation of the non-coding portion of the
      genome, in particular gene regulatory sequences. We have developed a new web
      based tool, TFBScluster, which performs genome-wide identification of
      transcription factor binding site clusters that are conserved in multiple
      mammalian genomes. Clusters representing candidate gene regulatory elements can
      be filtered further, based on the presence or absence of additional user-defined
      DNA sequence motifs or by constraining the orientation or order of binding sites.
      Comprehensive results files, returned by email, are designed to facilitate
      experimental validation of computationally identified candidate gene regulatory
      sequences. TFBScluster, therefore, has the potential to contribute to deciphering
      transcriptional networks that regulate a wide range of mammalian developmental
      processes.

PMID- 15855249
TI  - Deltarho-web, an online tool to assess composition similarity of individual
      nucleic acid sequences.
AB  - SUMMARY: Although whole-genome sequences have been analysed for the presence of
      anomalous DNA, no dedicated application is currently available to analyse the
      composition of individual sequence entries, for instance those derived by
      experimental techniques, such as subtractive hybridization. Since genomic
      dinucleotide frequency values are conserved between related species, a
      representative genome sequence can often be found to score for anomalous sequence
      composition for many of these putative horizontally transferred sequences. We
      developed the application deltarho-web, which enables the determination of the
      differences between the dinucleotide composition of an input sequence and that of
      a selected genome in a size-dependent manner. A feature allowing batch
      comparisons is included as well. In addition, deltarho-web allows the analysis of
      the dinucleotide composition of complete genomes. This provides complementary
      information for the identification of large anomalous gene clusters.

PMID- 15855250
TI  - Association mapping and fine mapping with TreeLD.
AB  - SUMMARY: The program package TreeLD implements a unified approach to association
      mapping and fine mapping of complex trait loci and a novel approach to
      visualizing association data, based on an inferred ancestry of the sample.
      Fundamentally, the TreeLD approach is based on the idea that the evidence for
      association at a particular position is contained in the ancestral tree relating
      the sampled chromosomes at that position. TreeLD provides an easy-to-use
      interface and can be applied to case-control, TDT trio and quantitative trait
      data.

PMID- 15855251
TI  - Prediction of protein-protein interactions by combining structure and sequence
      conservation in protein interfaces.
AB  - MOTIVATION: Elucidation of the full network of protein-protein interactions is
      crucial for understanding of the principles of biological systems and processes.
      Thus, there is a need for in silico methods for predicting interactions. We
      present a novel algorithm for automated prediction of protein-protein
      interactions that employs a unique bottom-up approach combining structure and
      sequence conservation in protein interfaces. RESULTS: Running the algorithm on a
      template dataset of 67 interfaces and a sequentially non-redundant dataset of
      6170 protein structures, 62 616 potential interactions are predicted. These
      interactions are compared with the ones in two publicly available interaction
      databases (Database of Interacting Proteins and Biomolecular Interaction Network
      Database) and also the Protein Data Bank. A significant number of predictions are
      verified in these databases. The unverified ones may correspond to (1)
      interactions that are not covered in these databases but known in literature, (2)
      unknown interactions that actually occur in nature and (3) interactions that do
      not occur naturally but may possibly be realized synthetically in laboratory
      conditions. Some unverified interactions, supported significantly with studies
      found in the literature, are discussed. AVAILABILITY:
      http://gordion.hpc.eng.ku.edu.tr/prism CONTACT: agursoy@ku.edu.tr;
      okeskin@ku.edu.tr.

PMID- 15855252
TI  - The metabolically healthy but obese individual presents a favorable inflammation
      profile.
AB  - OBJECTIVE: The purpose of this study was to investigate the inflammatory state in
      obese women displaying the "metabolically healthy but obese" (MHO) phenotype.
      DESIGN: We examined the metabolic characteristics of 88 obese, sedentary
      postmenopausal women. Subjects were classified as MHO or as "at risk" based on
      the upper and lower quartiles of insulin sensitivity as measured by the
      hyperinsulinemic-euglycemic clamp technique. Thereafter, we determined 1) body
      composition, 2) body fat distribution, 3) plasma lipid and lipoprotein levels, 4)
      glucose homeostasis, 5) resting blood pressure, 6) peak oxygen consumption, and
      7) inflammation markers as potential modulators of differences in the coronary
      risk profile. RESULTS: Twenty-two MHO women displayed high insulin sensitivity
      (15.35 +/- 2.3 mg/min.kg fat-free mass), and 22 at risk subjects with low insulin
      sensitivity (7.98 +/- 1.4 mg/min.kg fat-free mass) were identified. Despite
      comparable total body fatness between groups (47.7 +/- 4.8 vs. 45.5 +/- 4.4%; not
      significant), MHO individuals had significantly lower levels of visceral fat,
      fasting insulin, plasma triglycerides, high-sensitivity C-reactive protein (CRP),
      and alpha-1 antitrypsin levels and higher levels of high-density lipoprotein
      cholesterol than at risk individuals (P < 0.05). Stepwise regression analysis
      showed that CRP, fasting triglycerides, and the lean body mass index explained
      19.5, 8.5, and 4.0%, respectively, of the variance observed in glucose disposal
      (total r(2) = 0.320; P < 0.001). CONCLUSION: Results of the present study
      indicate that postmenopausal women displaying the MHO phenotype also have a
      favorable inflammation profile as shown by lower CRP and alpha-1 antitrypsin
      levels compared with insulin-resistant women. This suggests that a lower
      inflammation state, as attested by low CRP levels, could play a role in the
      protective profile of the MHO individual, and this may be associated
      metabolically to a lower risk for cardiovascular disease.

PMID- 15855253
TI  - Innate and acquired immune system in patients developing interferon-alpha-related
      autoimmune thyroiditis: a prospective study.
AB  - OBJECTIVE: In this prospective study, we investigated whether the development of
      interferon (IFN)-alpha-related autoimmune thyroiditis (IFN-AT) was correlated
      with the sequential changes of cytokine pattern induced by IFNalpha in the
      peripheral lymphocytes. PATIENTS AND METHODS: We enrolled 18 hepatitis C virus
      (HCV)-positive patients who developed IFN-AT, eight patients with euthyroidism
      [IFN-AT(Eu)] and 10 with thyroid dysfunction [IFN-AT(Dy)]. Twenty HCV-positive
      patients without IFN-AT acted as control group (Co-HCV+). Intracellular
      expression of IFNgamma and IL-4 was evaluated by multicolor flow-cytometry
      analysis in peripheral lymphocytes in vitro stimulated by phorbol-12-myristate-13
      acetate (PMA) (25 ng/ml) and ionomycin (1 mug/ml) in presence of monensin (5
      microm). RESULTS: At the appearance of thyroid disease, both IFN-AT(Eu) and IFN
      AT(Dy) patients showed a significant increase of IFNgamma expression in CD3+CD56+
      and CD3-CD56+ cells but not in CD4+ and CD8+ cells. At this time point, IFN
      AT(Eu) but not IFN-AT(Dy) patients also showed an increase of IL-4 expression in
      CD3+CD56+ cells and CD4+ cells. Six months later, IFN-AT(Eu) patients maintained
      high expression of IL-4 in CD4+ and CD3+CD56+ cells without any further increase
      in IFNgamma expression. By contrast, IFN-AT(Dy) patients showed an increase of
      IFNgamma expression in CD4+ and CD8+ cells, with a concomitant decrease of IL-4
      expression in CD4+ cells. CONCLUSIONS: Type 2 immune response is activated early
      and specifically in patients with IFN-AT who remain euthyroid throughout the
      follow-up. Predominant in patients developing thyroid dysfunction, by contrast,
      is the type 1 immune response that seems to occur earlier in innate than acquired
      immune system.

PMID- 15855254
TI  - Liver fat and insulin resistance are independently associated with the -514C>T
      polymorphism of the hepatic lipase gene.
AB  - CONTEXT: Liver fat predicts insulin resistance in humans. So far, there is not
      much information on genetic determinants of liver fat. Hepatic lipase is a liver
      specific enzyme that regulates lipid metabolism. OBJECTIVE: First, our object was
      to investigate whether the functional -514C>T polymorphism of the hepatic lipase
      gene is associated with liver fat content and with insulin sensitivity. Second,
      because this polymorphism displays gene-nutrient interactions, we assessed gene
      gene interactions with the Pro12Ala polymorphism of the peroxisome proliferator
      activated receptor-gamma(2) on liver fat content and insulin sensitivity. DESIGN
      AND METHODS: Cross-sectional data from a total of 1070 nondiabetic subjects were
      analyzed. Insulin sensitivity was estimated from a 75-g oral glucose tolerance
      test. A subgroup of 115 subjects underwent measurements of liver fat. RESULTS:
      The -514C>T polymorphism of the hepatic lipase gene was associated with higher
      liver fat content (P = 0.005) and lower insulin sensitivity (P = 0.02), both
      after adjustment for age, gender, and percentage of body fat. This was
      independent of serum adiponectin concentrations (P = 0.01 and 0.03). However,
      there was an interaction of the -514C>T polymorphism with the Pro12Ala variant on
      liver fat (P = 0.09) and insulin sensitivity (P = 0.01). Subjects carrying the 
      514C>T polymorphism had higher liver fat content and were insulin resistant only
      before the background of the Pro/Pro genotype of the Pro12Ala polymorphism.
      CONCLUSIONS: The -514C>T polymorphism of the hepatic lipase gene is associated
      with higher liver fat content and lower whole-body insulin sensitivity. However,
      these effects are modulated by the common Pro12Ala polymorphism in peroxisome
      proliferator-activated receptor-gamma(2). These findings may be relevant for
      intervention strategies to prevent increase in liver fat content and insulin
      resistance.

PMID- 15855255
TI  - Oxytocin inhibits T-type calcium current of human decidual stromal cells.
AB  - CONTEXT: Little is known about the crosstalk between the decidua and myometrium
      in relation to human labor. The hormone oxytocin (OT) is considered to be a key
      mediator of uterine contractility during parturition, exerting some of its
      effects through calcium channels. OBJECTIVE: The objective was to characterize
      the effect of OT on the T-type calcium channel in human decidual stromal cells
      before and after the onset of labor. DESIGN: The nystatin-perforated patch-clamp
      technique was used to record inward T-type calcium current (I(Ca(T))) from
      acutely dispersed decidual stromal cells obtained from women at either elective
      cesarean section [CS (nonlabor)] or after normal spontaneous vaginal delivery
      [SVD (labor)]. SETTING: These studies took place at the University of Nottingham
      Medical School. RESULTS: I(Ca(T)) of both SVD and CS cells were blocked by nickel
      (IC(50) of 5.6 microm) and cobalt chloride (1 mm) but unaffected by nifedipine
      (10 microm). OT (1 nm to 3.5 microm) inhibited I(Ca(T)) of SVD cells in a
      concentration-dependent manner, with a maximal inhibition of 79.0% compared with
      26.2% in decidual cells of the CS group. OT-evoked reduction of I(Ca(T)) was
      prevented by preincubation with the OT antagonist L371,257 in the SVD but not CS
      group. OT, in a concentration-dependent manner, displaced the steady-state
      inactivation curve for I(Ca(T)) to the left in the SVD group with no significant
      effect on curves of the CS group. CONCLUSION: Inhibition of I(Ca(T)) by OT in
      decidual cells obtained during labor may signify important functional remodeling
      of uterine signaling during this period.

PMID- 15855256
TI  - Adiposity in relation to vitamin D status and parathyroid hormone levels: a
      population-based study in older men and women.
AB  - OBJECTIVE: In small case-control studies, obesity was associated with worse
      vitamin D status. Our aim was to assess the association of adiposity
      (anthropometric measures as well as dual energy x-ray absorptiometry) with serum
      25-hydroxyvitamin D (25-OH-D) and serum PTH levels in a large population-based
      study including older men and women. METHODS: Subjects were participants of the
      Longitudinal Aging Study Amsterdam and were aged 65 yr and older. In 453
      participants, serum 25-OH-D and PTH were determined, and body mass index, waist
      circumference, waist to hip ratio, sum of skin folds, and total body fat
      percentage by dual energy x-ray absorptiometry were measured. RESULTS: After
      adjustment for potential confounders, higher body mass index, waist
      circumference, and sum of skin folds were statistically significantly associated
      with lower 25-OH-D (standardized beta values were -0.136, -0.137, and -0.140,
      respectively; all P < 0.05) and with higher PTH (0.166, 0.113, and 0.114,
      respectively; all P < 0.05). Total body fat percentage was more strongly
      associated with 25-OH-D and PTH (-0.261 and 0.287, respectively; both P < 0.001)
      compared with anthropometric measures. Total body fat percentage remained
      associated with 25-OH-D after adjustment for PTH, and with PTH after adjustment
      for 25-OH-D. CONCLUSION: Precisely measured total body fat is inversely
      associated with 25-OH-D levels and is positively associated with PTH levels. The
      associations were weaker if anthropometric measures were used, indicating a
      specific role of adipose tissue. Regardless of the possible underlying
      mechanisms, it may be relevant to take adiposity into account when assessing
      vitamin D requirements.

PMID- 15855257
TI  - Limited efficacy of growth hormone (GH) during transition of GH-deficient
      patients from adolescence to adulthood: a phase III multicenter, double-blind,
      randomized two-year trial.
AB  - CONTEXT: Treatment of GH-deficient adolescents in transition to adulthood remains
      challenging. OBJECTIVE: The objective was to assess the safety and efficacy of GH
      in GH-deficient adolescents in transition. PATIENTS: Fifty-eight GH-deficient
      adolescents (mean age, 15.8 +/- 1.8 yr; 33 males) at near completion of their
      linear growth participated in the study. INTERVENTION: Baseline studies were done
      while subjects were on GH. Subjects were retested (insulin-induced hypoglycemia)
      4 wk after GH discontinuation and reclassified as persistently GH-deficient or
      controls (n = 18). GH-deficient subjects were randomized to GH (n = 25,
      approximately 20 microg/kg.d) or placebo (n = 15). SETTING: The multicenter study
      was conducted over a 2-yr period. MAIN OUTCOMES: Changes in body composition,
      bone mineral density (BMD), quality of life (QOL), cardiovascular and metabolic
      markers were measured. RESULTS: All groups had normal measures of lipid and
      carbohydrate metabolism, body composition, BMD, cardiac function, muscle
      strength, and QOL at baseline and after 2 yr. IGF-I concentrations decreased in
      all, but less so in the GH-group (P = 0.013). There was a greater increase in
      lean body mass (lesser adiposity) in the GH group than placebo at 12 months, but
      not at 24 months. CONCLUSIONS: 1) GH-deficient patients properly treated in
      childhood can have normal BMD, body composition, cardiac function, muscle
      strength, carbohydrate and lipid metabolism, and QOL when reaching adult height;
      and 2) continuation of GH therapy for 2 yr did not change these measures as
      compared to placebo-treated or control subjects. GH-deficient adolescents in good
      metabolic status at the time of epiphyseal fusion may safely discontinue GH for
      at least 2 yr. Follow-up is needed to determine whether GH therapy is eventually
      warranted in subjects treated with GH during childhood.

PMID- 15855258
TI  - Comparison of the metabolic effects of raloxifene and oral estrogen in
      postmenopausal and growth hormone-deficient women.
AB  - CONTEXT: The endocrine and metabolic functions of the liver are affected by
      estrogen. Oral estrogen reduces IGF-I and suppresses fat oxidation despite
      augmenting GH secretion. The aim of this study was to determine whether selective
      estrogen receptor modulators display similar effects and whether these effects
      are magnified in GH-deficient (GHD) women because of the loss of GH feedback.
      DESIGN: This was an open-label, randomized, two-period, crossover study comparing
      treatment (raloxifene vs. estradiol) and group (normal vs. GHD). SETTING: The
      setting of this study was a clinical research unit. PARTICIPANTS: Twelve
      postmenopausal women and 12 women with hypopituitarism participated in this
      study. INTERVENTION: Two 4-wk treatments with 17beta-estradiol (E2; 2 mg,
      followed by 4 mg) or raloxifene (60 mg, followed by 120 mg) were given, crossing
      over to the alternate treatment after a 4-wk washout period. OUTCOME MEASURES:
      Endocrine [GH, IGF-I, IGF-binding protein-3 (IGFBP-3), GH-binding protein, and
      SHBG] and metabolic (fat oxidation) end points were used as outcome measures.
      RESULTS: E2 reduced serum IGF-I levels in a dose-dependent manner in both groups,
      with effects greater (P < 0.05) than raloxifene. Raloxifene reduced IGF-I levels
      in the GHD group (P < 0.001), but not in the postmenopausal group. E2 reduced (P
      < 0.05), and raloxifene increased (P < 0.05), IGFBP-3 levels in both groups. E2,
      but not raloxifene, increased GH (P < 0.05) in postmenopausal women. The effects
      of E2 and raloxifene on IGF-I, IGFBP-3, IGF-I/IGFBP-3 molar ratio, GH-binding
      protein, and SHBG were significantly different (P < 0.05). E2 and raloxifene
      reduced (P < 0.05) fat oxidation equally in GHD, whereas the decrease in
      postmenopausal women was not significant. CONCLUSION: E2 and raloxifene exert
      different hepatic endocrine, but not lipid oxidative, effects. The greater
      effects seen in GHD women may be explained by the loss of endogenous GH feedback.

PMID- 15855259
TI  - Ovarian function during puberty in girls with type 1 diabetes mellitus: response
      to leuprolide.
AB  - CONTEXT: An increased prevalence of polycystic ovary syndrome (PCOS) has been
      reported in adult women with type 1 diabetes mellitus (DM1). We investigated
      whether these hormonal abnormalities begin during puberty by evaluating the
      ovarian steroidogenic response to leuprolide acetate. METHODS: We studied 56
      adolescent girls with DM1 (aged 12.3 +/- 0.2 yr) and 64 healthy girls (C) (aged
      11.9 +/- 0.2 yr) up to 2 yr post menarche, matched by age, body mass index, and
      pubertal development. We evaluated anthropometrical data and Ferriman-Gallway
      score and performed a leuprolide test (500 microg sc) to study ovarian function.
      Ovarian volume was determined by transabdominal ultrasonography. RESULTS: We
      found five DM1 but no C girls with abnormally located terminal hair (Fisher's
      exact, P < 0.05). Free androgen index increased throughout puberty in girls with
      DM1 (ANOVA, P < 0.0001), which was associated with a decrease in SHBG levels in
      girls with DM1 (ANOVA, P < 0.0001). Stimulated 17OH progesterone (17OHProg)
      increased throughout puberty only in girls with DM1 (ANOVA, P < 0.01). Girls with
      DM1 at Tanner stage 5 had higher stimulated LH to FSH ratio, testosterone, and
      17OHProg levels than girls at Tanner stage 4. In contrast, in C girls the
      stimulated testosterone, 17OHProg, and LH to FSH ratio were similar at Tanner
      stages 4 and 5. Ovarian volumes and uterine length were larger in girls with DM1
      (analysis of covariance, P < 0.05). CONCLUSIONS: These data suggest that patients
      with DM1 have differences in ovarian steroidogenic response to leuprolide,
      compared with C girls during puberty. Future studies in young women should
      clarify whether these findings are related to the pathogenesis of
      hyperandrogenism later in life.

PMID- 15855260
TI  - Pyruvate dehydrogenase phosphatase deficiency: identification of the first
      mutation in two brothers and restoration of activity by protein complementation.
AB  - CONTEXT: Pyruvate dehydrogenase phosphatase (PDP) deficiency has been previously
      reported as an enzymopathy, but the genetic basis for such a defect has never
      been established. OBJECTIVE: The aim of this study was to identify the cause of
      the defect in two patients who presented with PDP deficiency. PATIENTS: We
      studied two brothers of consanguineous parents who presented with neonatal
      hypotonia, elevated lactate, and less than 25% native pyruvate dehydrogenase
      complex (PDHc) activity in skin fibroblasts compared with controls. The activity
      of the complex could be restored to normal values by preincubation of the cells
      with dichloroacetate or by treating cell extracts with calcium. RESULTS: These
      two individuals were found to be homozygous for a 3-bp deletion in the coding
      sequence of the PDP isoform 1 (PDP1), which removes the amino acid residue
      leucine from position 213 of the protein. A recombinant version of this protein
      was synthesized and found to have a very reduced (<5%) ability to activate
      purified PDHc. Reduced steady-state levels of PDP1 in the patient's fibroblasts
      coupled with the low catalytic activity of the mutant PDP1 resulted in native
      PDHc activity being reduced, but this could be corrected by the addition of
      recombinant PDP1 (wild type). CONCLUSION: We have identified mutations in PDP1 in
      two brothers with PDP deficiency and have proven that the mutation is disease
      causing. This is the first demonstration of human disease due to a mutation in
      PDP1.

PMID- 15855261
TI  - The effect of the Ala12 allele of the peroxisome proliferator-activated receptor
      gamma2 gene on skeletal muscle glucose uptake depends on obesity: a positron
      emission tomography study.
AB  - CONTEXT: The Pro(12)Ala polymorphism of the peroxisome proliferator-activated
      receptor-gamma2 gene is associated with insulin sensitivity. Obesity is a major
      risk factor for insulin resistance, but the association of the Pro(12)Ala
      polymorphism with body weight has been controversial. Furthermore, obesity may
      modulate the effect of this polymorphism on insulin sensitivity. OBJECTIVE: The
      aim of our study was to investigate the effects of the Pro(12)Ala polymorphism on
      skeletal muscle and adipose tissue glucose uptake (GU) in nonobese and obese
      subjects. DESIGN: The design was a cross-sectional study. STUDY SUBJECTS: The
      rates of GU were investigated in 124 (72 nonobese and 52 obese; body mass index
      cutoff point, 27 kg/m(2)) healthy subjects with the euglycemic hyperinsulinemic
      clamp. Skeletal muscle and adipose tissue GU and skeletal muscle perfusion were
      measured using fluorine-18-labeled fluorodeoxyglucose, [(15)O]H(2)O, and positron
      emission tomography. RESULTS: The rates of skeletal muscle GU were higher in
      nonobese subjects carrying the Ala(12) allele than in subjects carrying the
      Pro(12)Pro genotype (P = 0.004), whereas no differences were found in skeletal
      muscle perfusion between the groups. In contrast, in obese subjects the rates of
      skeletal muscle GU did not differ between carriers of the Ala(12) allele and
      carriers of the Pro(12)Pro genotype. No difference in adipose tissue GU was found
      in either nonobese or obese subjects according to Pro(12)Ala polymorphism.
      CONCLUSIONS: We conclude that the Pro(12)Ala polymorphism modulates skeletal
      muscle GU differently in nonobese and obese subjects.

PMID- 15855262
TI  - Dramatic elevations of interleukin-6 and acute-phase reactants in athletes
      participating in the ultradistance foot race spartathlon: severe systemic
      inflammation and lipid and lipoprotein changes in protracted exercise.
AB  - CONTEXT AND OBJECTIVE: Plasma IL-6, the serum inflammatory markers C-reactive
      protein (CRP) and serum amyloid A (SAA), and the tissue destruction marker-free
      plasma DNA, as well as the circulating lipid profile, were examined in athletes
      participating in the ultradistance foot race of the 246-km Spartathlon. SETTING,
      DESIGN, AND PARTICIPANTS: This race consists of continuous, prolonged, brisk
      exercise. Blood samples were obtained from 15 male athletes, who finished the
      race in less than 36 h, taken before, at the end of, and 48 h after the end of
      the race. RESULTS: IL-6, CRP, SAA, and free plasma DNA levels markedly increased
      (by 8000-, 152- 108-, and 10-fold, respectively) over the baseline at the end of
      the race. However, IL-6 levels returned to normal by 48 h, whereas CRP, SAA, and
      free plasma DNA remained elevated. The mean values of cholesterol, triglycerides,
      low-density lipoprotein, and apolipoprotein B decreased to a minimum value at the
      end of the race and remained low 48 h after the race. High-density lipoprotein
      levels, on the other hand, were mildly increased at the end of the race (P <
      0.015) and decreased to normal 48 h after the race. Apolipoprotein AI levels
      decreased significantly during the time course of the exercise and remained low
      48 h after the race (P < 0.001). CONCLUSIONS: These observations suggest that
      continuous, prolonged, moderate-intensity exercise is associated with markedly
      elevated IL-6 and acute-phase reactant concentrations, peripheral tissue damage,
      and significant changes in serum lipid levels. The biochemical changes observed
      during the Spartathlon amount to a potent systemic inflammatory response, which
      might explain severe cardiovascular events that occur during prolonged exercise
      in compromised individuals.

PMID- 15855263
TI  - Muscle metabolism and exercise tolerance in subclinical hypothyroidism: a
      controlled trial of levothyroxine.
AB  - BACKGROUND: Neuromuscular symptoms and impaired muscle energy metabolism have
      been described in subclinical hypothyroidism (sHT). AIM: The aim of the study was
      to evaluate the energy and substrate response to exercise in sHT patients using a
      standardized protocol and to test the effect of L-T(4) replacement in a double
      blind, randomized, placebo-controlled fashion. PATIENTS AND METHODS: We studied
      23 sHT patients and 10 matched euthyroid controls. Oxygen uptake (VO(2)), carbon
      dioxide output, and heart rate were measured during incremental step-up exercise.
      Blood glucose, lactate, pyruvate, free fatty acid, glycerol, and beta
      hydroxybutyrate concentrations were measured at rest, every 2 min during
      exercise, and during 20 min of recovery. The exercise protocol was repeated after
      6 months of placebo or L-T(4)-restored euthyroidism. RESULTS: Maximal power
      output (P = 0.02) and VO(2) max (P = 0.04) were reduced in sHT, and, with
      increasing workload, patients achieved higher heart rates (P < 0.03) at VO(2)
      values equivalent to those of controls. The respiratory quotient increments were
      significantly higher in patients than controls (P < 0.04). Blood lactate and
      pyruvate and their ratio rose with a steeper slope (P < 0.0001, P < 0.001, and P
      < 0.01, respectively) in patients than controls. Resting plasma free fatty acid
      and blood glycerol levels were significantly higher in patients than controls (P
      < 0.0003 and P < 0.003, respectively) throughout baseline, exercise, and
      recovery. L-T(4) replacement, while improving neuromuscular symptoms, did not
      produce significant changes in the energy or substrate response to exercise.
      CONCLUSIONS: The response to exercise is altered both in terms of tolerance and
      pattern of substrate utilization in sHT patients. Restoring stable euthyroidism
      does not correct this defect over a 1-yr period.

PMID- 15855264
TI  - Association of adiponectin level and variants in the adiponectin gene with
      glucose metabolism, energy expenditure, and cytokines in offspring of type 2
      diabetic patients.
AB  - OBJECTIVE: Adiponectin is an adipose-specific secretory protein abundantly
      present in the circulation. The role of adiponectin in the control of energy
      expenditure and substrate utilization has not yet been established. DESIGN: We
      performed detailed metabolic studies in a large cohort (n = 158) of offspring of
      patients with type 2 diabetes (T2DM) to determine the association of adiponectin
      level with glucose and lipid oxidation, energy expenditure, insulin sensitivity,
      and visceral obesity by applying the euglycemic clamp technique and indirect
      calorimetry. RESULTS: The adiponectin level was lower in offspring of T2DM
      patients than in control subjects. When the data were analyzed by adiponectin
      tertiles, an elevated adiponectin level was associated with high total,
      oxidative, and nonoxidative glucose disposal and high energy expenditure during
      hyperinsulinemia; low levels of free fatty acids and low rates of lipid oxidation
      during hyperinsulinemia; as well as low levels of inflammatory cytokines; and a
      low amount of intraabdominal fat evaluated by computed tomography. No association
      of single nucleotide polymorphism 45 or single nucleotide polymorphism 276 with
      adiponectin level was found. CONCLUSIONS: We conclude that adiponectin has
      multiple effects on glucose, lipid and free fatty acid metabolism, and cytokines
      in offspring of T2DM subjects.

PMID- 15855265
TI  - AKT is highly phosphorylated in pheochromocytomas but not in benign
      adrenocortical tumors.
AB  - CONTEXT: Activation of AKT plays a major role in a variety of human neoplasias.
      In mice, a heterozygous deletion of the Pten gene is associated with increased
      activation of AKT and with development of pheochromocytomas. OBJECTIVE: The
      objective of this study was the investigation of the role of AKT in the
      pathogenesis of pheochromocytomas and adrenocortical tumors. DESIGN, SETTING, AND
      PARTICIPANTS: Total AKT and phosphorylated AKT (pAKT) in 15 pheochromocytomas,
      nine aldosterone-producing adenomas, nine cortisol-producing adenomas, eight
      adrenocortical carcinomas (ACC), and 15 normal adrenals were investigated by
      Western blot analysis. Immunohistochemistry for total AKT and pAKT was performed
      in pheochromocytomas (n = 8), ACC (n = 4), and normal adrenal glands (n = 2). In
      addition, in pheochromocytomas PTEN protein expression and PTEN loss of
      heterozygosity were analyzed. MAIN OUTCOME MEASURES: Determination of pAKT/total
      AKT ratio in adrenal tissues was the main outcome. RESULTS: In comparison to
      normal adrenals, total AKT expression was elevated in both pheochromocytomas (193
      +/- 22%) and ACC (176 +/- 36%). The pAKT/AKT ratio was significantly increased in
      pheochromocytomas (338 +/- 49% vs. 100 +/- 11%) but not in ACC, aldosterone
      producing adenomas, and cortisol-producing adenomas. No loss of heterozygosity of
      PTEN and no decrease in PTEN protein was detected in pheochromocytomas.
      Immunohistochemistry showed strong and homogeneous AKT and pAKT staining in
      pheochromocytomas and focal staining in ACC. CONCLUSION: Our findings provide
      evidence for increased activation of AKT in pheochromocytomas but not in
      adrenocortical adenomas.

PMID- 15855266
TI  - Median eminence dopaminergic nerve terminals: a novel target in autoimmune
      polyendocrine syndrome?
AB  - CONTEXT: Autoantibodies to adenohypophyseal endocrine cells or to vasopressin
      neurohypophyseal neurons have long been known. Conversely, autoimmune targeting
      of further hypothalamic-hypophyseal structures, such as the blood-brain barrier
      deprived median eminence, has been little studied. OBJECTIVE AND METHODS: We
      studied a case of autoimmune polyendocrine syndrome type I with GH secretory
      deficiency, a distinctly rare event in autoimmune polyendocrine syndrome type I.
      We used rat and bovine tissue substrates to study autoantibodies against
      hypothalamic-hypophyseal nerve structures and endocrine cells. RESULTS: In the
      study case, circulating autoantibodies selectively decorated median eminence
      dopaminergic nerve terminals, as well as pituitary gonadotropes, but not GHRH
      nerve terminals or pituitary somatotropes. Such autoantibodies appeared de novo
      in parallel with the onset of GH secretory deficiency, whereas no median eminence
      labeling was found in patients suffering of idiopathic GH deficiency (n = 7) or
      in healthy controls (n = 23). CONCLUSIONS: The pathophysiological significance of
      our patient's autoantibodies remains to be confirmed. Nonetheless, the
      heterogeneous neuroendocrine structures of the median eminence are pointed out as
      potential immune targets, relevant to autoimmune polyendocrinopathy, as well as
      to a wide range of other conditions.

PMID- 15855267
TI  - Circulating leptin correlates with left ventricular mass in morbid (grade III)
      obesity before and after weight loss induced by bariatric surgery: a potential
      role for leptin in mediating human left ventricular hypertrophy.
AB  - CONTEXT: Obesity is frequently associated with left ventricular hypertrophy, even
      when uncomplicated by hypertension or diabetes mellitus. Left ventricular
      hypertrophy is an important risk factor for congestive heart failure. OBJECTIVE:
      The objective of this study was to evaluate the relationship between leptin and
      left ventricular mass in uncomplicated, morbid (grade 3) obesity and the
      existence of leptin receptors and intracellular signaling proteins in the human
      heart. DESIGN: Left ventricular mass (LVM) was calculated through
      electrocardiogram reading in normotensive grade III obese patients (World Health
      Organization classification) undergoing bariatric surgery [laparoscopic
      adjustable gastric banding (LAGB)] at baseline and 1 yr later. The control group
      was composed of healthy lean normotensive subjects. Leptin receptors were
      detected by PCR and immunocytochemistry in human heart biopsies. SETTING: This
      study was performed at university hospitals. PATIENTS: Thirty-one grade 3 obese
      patients and 30 healthy nonobese normotensive, age- and sex-matched control
      subjects were studied. INTERVENTION: Obese subjects underwent LAGB to induce
      weight loss and were evaluated at baseline and after 1 yr. RESULTS: LVM, plasma
      leptin, glucose, insulin levels, and homeostasis model assessment index were
      higher in obese than in lean controls (P < 0.01); at univariate regression
      analysis, LVM correlated with body mass index, leptin, and homeostasis model
      assessment index; at multiple regression analysis, LVM only correlated with
      leptin levels (P = 0.001). Obese subjects were reevaluated 1 yr after LAGB, when
      their body mass index changed from 46.2 +/- 1.24 to 36.6 +/- 1.05 kg/m(2) (P <
      0.01); the decrease in LVM correlated only with the decrease in leptin levels (P
      < 0.01). We demonstrated that long and short isoforms of the leptin receptor and
      intracellular proteins mediating leptin signaling were expressed in human heart
      by RT-PCR, immunocytochemistry, or both methods. CONCLUSIONS: These data suggest
      that leptin could contribute to the left ventricular hypertrophy in humans.

PMID- 15855268
TI  - Expression and regulation of adiponectin and receptor in human and rat placenta.
AB  - CONTEXT: Adiponectin is an adipocyte hormone involved in glucose and lipid
      metabolism. Recently, two receptors of this protein, called adiponectin receptor
      1 (Adipo-R1) and Adipo-R2, have been cloned. OBJECTIVE: The aim of this study was
      to examine whether adiponectin and its receptors are expressed in human and rat
      placentas and to evaluate the regulation of these factors by gestational age and
      nutritional status. RESULTS: Our results demonstrate that adiponectin and Adipo
      R2 are localized in both human and rat placentas. Human adiponectin and Adipo-R2
      are presented in cytotrophoblast and syncytiotrophoblast cells. However, rat
      adiponectin and Adipo-R2 change their specific cell type immunostaining during
      gestation. Furthermore, placental adiponectin mRNA expression is increased during
      pregnancy in the rat, whereas Adipo-R2 has the contrary pattern. We also assessed
      the effect of food restriction (30%) during gestation, and we observed that
      adiponectin mRNA levels decrease after 16 d of undernutrition. In contrast,
      placental Adipo-R2 mRNA is unchanged by undernutrition. Finally, treatment with
      adiponectin during gestation decreases Adipo-R2, glucose transporter 3,
      lipoprotein lipase, and TGF-beta mRNA expression. CONCLUSION: Taken together, our
      results suggest that, at least in rodents, adiponectin may be involved in the
      regulation of several placental functions.

PMID- 15855269
TI  - A transcriptional response to singlet oxygen, a toxic byproduct of
      photosynthesis.
AB  - The ability of phototrophs to convert light into biological energy is critical
      for life on Earth. However, there can be deleterious consequences associated with
      this bioenergetic conversion, including the production of toxic byproducts. For
      example, singlet oxygen (1O2) can be formed during photosynthesis by energy
      transfer from excited triplet-state chlorophyll pigments to O2. By monitoring
      gene expression and growth in the presence of 1O2, we show that the phototrophic
      bacterium Rhodobacter sphaeroides mounts a transcriptional response to this
      reactive oxygen species (ROS) that requires the alternative sigma factor,
      sigma(E). An increase in sigma(E) activity is seen when cells are exposed to 1O2
      generated either by photochemistry within the photosynthetic apparatus or the
      photosensitizer, methylene blue. Wavelengths of light responsible for the
      generating triplet-state chlorophyll pigments in the photosynthetic apparatus are
      sufficient for a sustained increase in sigma(E) activity. Continued exposure to
      1O2 is required to maintain this transcriptional response, and other ROS do not
      cause a similar increase in sigma(E)-dependent gene expression. When a sigma(E)
      mutant produces low levels of carotenoids, 1O2 is bacteriocidal, suggesting that
      this response is essential for protecting cells from this ROS. In addition,
      global gene expression analysis identified approximately 180 genes (approximately
      60 operons) whose RNA levels increase > or = 3-fold in cells with increased
      sigma(E) activity. Gene products encoded by four newly identified sigma(E)
      dependent operons are predicted to be involved in stress response, protecting
      cells from 1O2 damage, or the conservation of energy.

PMID- 15855270
TI  - The retinal chromophore/chloride ion pair: structure of the photoisomerization
      path and interplay of charge transfer and covalent states.
AB  - Ab initio multi-reference second-order perturbation theory computations are used
      to explore the photochemical behavior of two ion pairs constituted by a chloride
      counterion interacting with either a rhodopsin or bacteriorhodopsin chromophore
      model (i.e., the 4-cis-gamma-methylnona-2,4,6,8-tetraeniminium and all-trans-nona
      2,4,6,8-tetraeniminium cations, respectively). Significant counterion effects on
      the structure of the photoisomerization paths are unveiled by comparison with the
      paths of the same chromophores in vacuo. Indeed, we demonstrate that the
      counterion (i) modulates the relative stability of the S0, S1, and S2 energy
      surfaces leading to an S1 isomerization energy profile where the S1 and S2 states
      are substantially degenerate; (ii) leads to the emergence of significant S1
      energy barriers along all of the isomerization paths except the one mimicking the
      11-cis --> all-trans isomerization of the rhodopsin chromophore model; and (iii)
      changes the nature of the S1 --> S0 decay funnel that becomes a stable excited
      state minimum when the isomerizing double bond is located at the center of the
      chromophore moiety. We show that these (apparently very different) counterion
      effects can be rationalized on the basis of a simple qualitative electrostatic
      model, which also provides a crude basis for understanding the behavior of
      retinal protonated Schiff bases in solution.

PMID- 15855271
TI  - Implications of the serine protease HtrA1 in amyloid precursor protein
      processing.
AB  - The defining features of the widely conserved HtrA (high temperature requirement)
      family of serine proteases are the combination of a catalytic protease domain
      with one or more C-terminal PDZ domains and reversible zymogen activation. Even
      though HtrAs have previously been implicated in protein quality control and
      various diseases, including cancer, arthritis, and neuromuscular disorder, the
      biology of the human family members is not well understood. Our data suggest that
      HtrA1 is directly involved in the beta-amyloid pathway as it degrades various
      fragments of amyloid precursor protein while an HtrA1 inhibitor causes
      accumulation of Abeta in astrocyte cell culture supernatants. Furthermore, HtrA1
      colocalizes with beta-amyloid deposits in human brain samples. Potential
      implications in Alzheimer's disease are discussed.

PMID- 15855272
TI  - Stem cell factor promotes mast cell survival via inactivation of FOXO3a-mediated
      transcriptional induction and MEK-regulated phosphorylation of the proapoptotic
      protein Bim.
AB  - Mast cells are found in tissues throughout the body where they play important
      roles in the regulation of inflammatory responses. One characteristic feature of
      mast cells is their longevity. Although it is well established that mast cell
      survival is dependent on stem cell factor (SCF), it has not been described how
      this process is regulated. Herein, we report that SCF promotes mast cell survival
      through inactivation of the Forkhead transcription factor FOXO3a (forkhead box,
      class O3A) and down-regulation and phosphorylation of its target Bim (Bcl-2 [B
      cell lymphoma-2] interacting modulator of cell death), a Bcl-2 homology 3 (BH3)
      only proapoptotic protein. SCF induced a rapid and transient phosphorylation of
      Akt (protein kinase B) and FOXO3a. SCF treatment prevented up-regulation of Bim
      protein expression and led to increased Bim phosphorylation. Bim phosphorylation
      was inhibited by PD98059 and LY294002 treatment, suggesting the involvement of
      mitogen-activated protein kinase kinase/mitogen-activated protein kinase
      (MEK/MAPK) and phosphatidylinositol 3 (PI3)-kinase pathways in this process.
      Overexpression of phosphorylation-deficient FOXO3a caused an up-regulation of Bim
      and induced mast cell apoptosis even in the presence of SCF. Mast cell apoptosis
      induced by the phosphorylation-deficient FOXO3a was attenuated in bim-/- mast
      cells. Because apoptosis is abnormally reduced in bim-/- mast cells, these data
      provide evidence that Akt-mediated inhibition of FOXO3a and its transcription
      target Bim provides an important mechanism by which SCF acts to prevent apoptosis
      in mast cells.

PMID- 15855273
TI  - Osteopontin functionally activates dendritic cells and induces their
      differentiation toward a Th1-polarizing phenotype.
AB  - Osteopontin (OPN) has been shown to have T helper 1 (Th1) cytokine functions in
      cell-mediated immunity. Deficiency of OPN is linked to a reduced Th1 immune
      response in autoimmunity, infectious disease, and delayed-type allergy. Dendritic
      cells (DCs) are central for the induction of T-cell-mediated immunity, when
      initially flexible DCs are instructed by priming signals and tissue-derived
      factors to adopt Th1, Th2, or regulatory T-cell-inducing phenotypes. Although OPN
      influences the cytokine secretion of T cells and macrophages, its effects on DC
      polarization remain an important missing link in the understanding of OPN
      functions in Th1 immunity. Here we demonstrate that OPN promotes the emigration
      of human DCs from the epidermis and functionally activates myeloid-type DCs,
      augmenting their expression of HLA-DR, costimulatory, and adhesion molecules. OPN
      induces their Th1-promoting tumor necrosis factor alpha (TNF-alpha) and
      interleukin-12 (IL-12) secretion, and enhances their allostimulatory capacity. In
      mixed lymphocyte reactions (MLRs), OPN stimulates IL-12 secretion by DCs,
      inducing elevated interferon-gamma (IFN-gamma) production by T cells. Naive Th
      cells stimulated by OPN-activated DCs show a Th1-polarized cytokine production.
      Our findings identify OPN as an important tissue-derived factor that DCs
      encounter when traveling from peripheral sites of activation to secondary
      lymphatic organs, which induces DC maturation toward a Th1-promoting phenotype.

PMID- 15855274
TI  - Serum free light chain ratio is an independent risk factor for progression in
      monoclonal gammopathy of undetermined significance.
AB  - We hypothesized that the presence of monoclonal free kappa or lambda
      immunoglobulin light chains in monoclonal gammopathy of undetermined significance
      (MGUS), as detected by the serum free light chain (FLC) assay increases the risk
      of progression to malignancy. Of 1384 patients with MGUS from Southeastern
      Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples
      obtained within 30 days of diagnosis were available in 1148. At a median follow
      up of 15 years, malignant progression had occurred in 87 (7.6%) patients. An
      abnormal FLC ratio (kappa-lambda ratio < 0.26 or > 1.65) was detected in 379
      (33%) patients. The risk of progression in patients with an abnormal FLC ratio
      was significantly higher compared with patients with a normal ratio (hazard
      ratio, 3.5; 95% confidence interval [CI], 2.3-5.5; P < .001) and was independent
      of the size and type of the serum monoclonal (M) protein. Patients with an
      abnormal serum FLC ratio, non-immunoglobulin G (non-IgG) MGUS, and a high serum M
      protein level (> or = 15 g/L) had a risk of progression at 20 years of 58% (high
      risk MGUS) versus 37% with any 2 of these risk factors (high-intermediate risk),
      21% with one risk factor (low-intermediate risk), and 5% when none of the risk
      factors were present (low risk).

PMID- 15855275
TI  - In vivo analyses of early events in acute graft-versus-host disease reveal
      sequential infiltration of T-cell subsets.
AB  - Graft-versus-host disease (GVHD) is a major obstacle in allogeneic hematopoietic
      cell transplantation. Given the dynamic changes in immune cell subsets and tissue
      organization, which occur in GVHD, localization and timing of critical
      immunological events in vivo may reveal basic pathogenic mechanisms. To this end,
      we transplanted luciferase-labeled allogeneic splenocytes and monitored tissue
      distribution by in vivo bioluminescence imaging. High-resolution analyses showed
      initial proliferation of donor CD4+ T cells followed by CD8+ T cells in secondary
      lymphoid organs with subsequent homing to the intestines, liver, and skin.
      Transplantation of purified naive T cells caused GVHD that was initiated in
      secondary lymphoid organs followed by target organ manifestation in gut, liver,
      and skin. In contrast, transplanted CD4+ effector memory T (T(EM)) cells did not
      proliferate in secondary lymphoid organs in vivo and despite their in vitro
      alloreactivity in mixed leukocyte reaction (MLR) assays did not cause acute GVHD.
      These findings underline the potential of T-cell subsets with defined trafficking
      patterns for immune reconstitution without the risk of GVHD.

PMID- 15855276
TI  - The transcription factor Gli3 regulates differentiation of fetal CD4- CD8- double
      negative thymocytes.
AB  - Glioblastoma 3 (Gli3) is a transcription factor involved in patterning and
      oncogenesis. Here, we demonstrate a role for Gli3 in thymocyte development. Gli3
      is differentially expressed in fetal CD4- CD8- double-negative (DN) thymocytes
      and is most highly expressed at the CD44+ CD25- DN (DN1) and CD44- CD25- (DN4)
      stages of development but was not detected in adult thymocytes. Analysis of null
      mutants showed that Gli3 is involved at the transitions from DN1 to CD44+ CD25+
      DN (DN2) cell and from DN to CD4+ CD8+ double-positive (DP) cell. Gli3 is
      required for differentiation from DN to DP thymocyte, after pre-T-cell receptor
      (TCR) signaling but is not necessary for pre-TCR-induced proliferation or
      survival. The effect of Gli3 was dose dependent, suggesting its direct
      involvement in the transcriptional regulation of genes controlling T-cell
      differentiation during fetal development.

PMID- 15855277
TI  - A newly discovered human alpha-globin gene.
AB  - A previously undefined transcript with significant homology to the pseudo-alpha2
      region of the alpha-globin locus on human chromosome 16 was detected as part of
      an effort to better define the transcriptional profiles of human reticulocytes.
      Cloning and sequencing of that transcript (GenBank AY698022; named mu-globin)
      revealed an insert with a 423-nucleotide open reading frame. BLASTP and ClustalW
      and phylogenetic analyses of the predicted protein demonstrated a high level of
      homology with the avian alpha-D globin. In addition, the heme- and globin-binding
      amino acids of mu-globin and avian alpha-D globin are largely conserved. Using
      quantitative real-time polymerase chain reaction (PCR), mu-globin was detected at
      a level of approximately 0.1% that measured for alpha-globin in erythroid
      tissues. Erythroid-specific expression was detected by Northern blot analysis,
      and maximal expression during the erythroblast terminal differentiation was also
      detected. Despite this highly regulated pattern of mu-globin gene transcription,
      mu-globin protein was not detected by mass spectrometry. These results suggest
      the human genome encodes a previously unrecognized globin member of the avian
      alpha-D family that is transcribed in a highly regulated pattern in erythroid
      cells.

PMID- 15855278
TI  - Advances in the biology and therapy of diffuse large B-cell lymphoma: moving
      toward a molecularly targeted approach.
AB  - Diffuse large B-cell lymphoma (DLBCL) displays striking heterogeneity at the
      clinical, genetic, and molecular levels. Clinical prognostic models can define a
      population at high risk for relapse following empiric chemotherapy, although such
      models do not account for underlying biologic differences among tumors. Commonly
      observed genetic abnormalities that likely contribute to pathogenesis include
      translocations of BCL6, BCL2, cMYC, and FAS(CD95) mutations, and aberrant somatic
      hypermutation. Despite recent advances in empiric chemotherapy, including
      interval reduction of CHOP (cyclophosphamide, doxorubicin, vincristine,
      prednisone) and the incorporation of anti-CD20 monoclonal antibodies, a
      significant proportion of patients still die of their disease. Gene expression
      profiling has shed light on the molecular heterogeneity within DLBCL by
      highlighting similarities between subsets of tumors and normal B cells,
      identifying features associated with unfavorable responses to empiric combination
      chemotherapy, and defining robust subtypes with comprehensive transcriptional
      signatures. Such strategies have suggested distinct routes to lymphomagenesis and
      have identified promising rational therapeutic targets. Additional novel
      therapies under investigation include those targeting BCL6 and BCL2, as well as
      development of novel monoclonal antibody-based therapies. Our increasing
      molecular understanding of the heterogeneous subsets within DLBCL will likely
      improve the current empiric therapy of DLBCL by identifying rational therapeutic
      targets in specific disease subtypes.

PMID- 15855279
TI  - Evidence for a protective role of the Gardos channel against hemolysis in murine
      spherocytosis.
AB  - It has been shown that mice with complete deficiency of all 4.1R protein isoforms
      (4.1-/-) exhibit moderate hemolytic anemia, with abnormal erythrocyte morphology
      (spherocytosis) and decreased membrane stability. Here, we characterized the
      Gardos channel function in vitro and in vivo in erythrocytes of 4.1-/- mice.
      Compared with wild-type, the Gardos channel of 4.1-/- erythrocytes showed an
      increase in Vmax (9.75 +/- 1.06 vs 6.08 +/- 0.09 mM cell x minute; P < .04) and a
      decrease in Km (1.01 +/- 0.06 vs 1.47 +/- 1.02 microM; P < .03), indicating an
      increased sensitivity to activation by intracellular calcium. In vivo function of
      the Gardos channel was assessed by the oral administration of clotrimazole, a
      well-characterized Gardos channel blocker. Clotrimazole treatment resulted in
      worsening of anemia and hemolysis, with decreased red cell survival and increased
      numbers of circulating hyperchromic spherocytes and microspherocytes.
      Clotrimazole induced similar changes in 4.2-/- and band 3+/- mice, indicating
      that these effects of the Gardos channel are shared in different models of murine
      spherocytosis. Thus, potassium and water loss through the Gardos channel may play
      an important protective role in compensating for the reduced surface-membrane
      area of hereditary spherocytosis (HS) erythrocytes and reducing hemolysis in
      erythrocytes with cytoskeletal impairments.

PMID- 15855280
TI  - Localization of ADAMTS13 to the stellate cells of human liver.
AB  - Although the chromosomal localization (9q34) of the gene encoding the human form
      of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type-1
      motifs 13) and its exclusive expression in the liver have been established, the
      cells that produce this enzyme are yet to be determined. We investigated the
      expression of ADAMTS13 mRNA and protein in fresh frozen specimens obtained during
      liver biopsies of 8 patients with liver diseases. In situ hybridizations to
      localize ADAMTS13 mRNA showed positive signals exclusively in perisinusoidal
      cells with irregularly elongated dendritic processes extending between
      hepatocytes. Furthermore, ADAMTS13 was detected immunohistochemically in
      perisinusoidal cells, whereas no staining was observed in hepatocytes. The
      positive cells varied in shape from unipolar to dendritic with irregularly
      elongated cytoplasmic processes, features common to hepatic stellate cells
      (HSCs). Double-labeling experiments revealed that the ADAMTS13-positive cells
      also expressed alpha-smooth muscle actin, confirming that these cells were
      activated HSCs. These results suggest that HSCs may be major cells producing
      ADAMTS13 in human liver.

PMID- 15855281
TI  - CBFB-SMMHC is correlated with increased calreticulin expression and suppresses
      the granulocytic differentiation factor CEBPA in AML with inv(16).
AB  - The pericentric inversion of chromosome 16, inv(16)(p13q22), is associated with
      acute myeloid leukemia (AML) subtype M4Eo that is characterized by the presence
      of myelomonocytic blasts and atypical eosinophils. This rearrangement fuses the
      CBFB and MYH11 genes, with the latter encoding the smooth muscle myosin heavy
      chain (SMMHC). The myeloid transcription factor CCAAT/enhancer-binding protein
      alpha (CEBPA) is crucial for normal granulopoiesis. Alterations of structure and
      expression of CEBPA have been implicated in particular subtypes of AML. Here, we
      found that conditional expression of core-binding factor beta (CBFB)-SMMHC in
      U937 cells suppresses CEBPA protein expression and binding activity. However,
      CEBPA mRNA levels remained unchanged. No differences were detected in CEBPA mRNA
      levels in patients with inv(16) AML-M4Eo (n = 12) compared to patients with AML
      with a normal karyotype and M4 subtype (n = 6), whereas CEBPA protein and binding
      activity were significantly reduced in patients with CBFB-SMMHC. Furthermore,
      calreticulin, an inhibitor of CEBPA translation, was induced on mRNA and protein
      level in CBFB-SMMHC patients with AML and after expression of CBFB-SMMHC in the
      U937-cell system. Inhibition of calreticulin by siRNA restored CEBPA levels. Our
      results suggest that modulation of CEBPA by calreticulin represents a novel
      mechanism involved in the differentiation block in CBFB-SMMHC AML.

PMID- 15855282
TI  - Mind the gap! Insight from the first 5 years of the Circle of Research and
      Practice.
AB  - This article provides a summary of insight, thoughts, discussions, diversity, and
      lessons learned in the first 5 years of invited commentaries in this health
      promotion practice department, the Circle of Research and Practice. The summary
      is framed in the four persistent gaps that need attention if the circle of
      research and practice is to be unbroken: communication, accessibility,
      credibility, and expectations.

PMID- 15855283
TI  - Developing a process-evaluation plan for assessing health promotion program
      implementation: a how-to guide.
AB  - Process evaluation is used to monitor and document program implementation and can
      aid in understanding the relationship between specific program elements and
      program outcomes. The scope and implementation of process evaluation has grown in
      complexity as its importance and utility have become more widely recognized.
      Several practical frameworks and models are available to practitioners to guide
      the development of a comprehensive evaluation plan, including process evaluation
      for collaborative community initiatives. However, frameworks for developing a
      comprehensive process-evaluation plan for targeted programs are less common.
      Building from previous frameworks, the authors present a comprehensive and
      systematic approach for developing a process-evaluation plan to assess the
      implementation of a targeted health promotion intervention. Suggested elements
      for process-evaluation plans include fidelity, dose (delivered and received),
      reach, recruitment, and context. The purpose of this article is to describe and
      illustrate the steps involved in developing a process evaluation plan for any
      health promotion program.

PMID- 15855284
TI  - A review and synthesis of research evidence for self-efficacy-enhancing
      interventions for reducing chronic disability: implications for health education
      practice (part II).
AB  - Chronic diseases such as arthritis, diabetes, and heart disease that cause pain,
      functional impairment, social and emotional dysfunction, and premature loss of
      wage earnings constitute a challenging problem for American society. In the
      absence of any effective cure for these frequently progressive conditions, the
      secondary prevention of complications, which requires a high degree of
      communication and cooperation between patient and clinician, and improving
      quality of life and functional capacity through better disease self-management
      becomes critical and are key objectives of Healthy People 2010. Part I of this
      two-part article described the common clinical features of chronic disease, the
      diverse disease management strategies used for alleviating pain and preventing
      disability, and the role of self-efficacy as a framework for intervention. This
      companion article identifies and synthesizes the key research evidence for
      educational interventions designed to enhance individual self-efficacy
      perceptions and presents implications for improving practices in patient
      education for chronic diseases.

PMID- 15855285
TI  - "Thinking Like a Marketer": training for a shift in the mindset of the public
      health workforce.
AB  - The marketing mindset focuses a practitioner on systematically thinking through
      key issues before undertaking a health promotion campaign. The Thinking Like a
      Marketer training, developed by the National Training Collaborative for Social
      Marketing is a challenging method for health educators and promoters to apply
      their skills in innovative ways. Focus groups were conducted with former trainees
      to assess the impact of the training. Additional data were collected from members
      of the Association of State and Territorial Promotion Directors of Health
      Promotion and Public Health Education organization through a 10-item elicitation
      survey. Findings suggest that although participants gained greater sensitivity
      and appreciation for the social marketing research process, the major barrier to
      application in the workplace surrounded upper management. On-site technical
      assistance, mentoring, and follow-up were important training needs identified
      through the survey and focus groups.

PMID- 15855286
TI  - Using community-based participatory research methods to reach women with health
      messages: results from the North Carolina BEAUTY and Health Pilot Project.
AB  - This pilot study used a community-based participatory research approach to
      recruit and train five licensed cosmetologists from two beauty salons to deliver
      health promotion messages to their customers. Stylists attended a 4-hr workshop
      to develop skills for delivering targeted health messages. Educational displays
      in the salons reinforced these messages. Qualitative and quantitative methods
      assessed satisfaction, readiness to change, and self-reported health behavior
      changes in customers immediately postintervention and at 12 months. Trained
      stylists reported they would continue delivering health messages after the 7-week
      pilot was completed; 81% of customers read the educational displays, and 86% of
      customers talked with their cosmetologist about the Bringing Education and
      Understanding to You Project. At 12 months, 55% of customers reported making
      changes in their health because of the conversations they had with their
      cosmetologist. Customers who spoke more often with their cosmetologists about
      health also reported a higher percentage of self-reported behavior changes. It
      appears that trained licensed cosmetologists are effective in promoting health
      messages to their customers.

PMID- 15855287
TI  - A cost-benefit analysis of physical activity using bike/pedestrian trails.
AB  - From a public health perspective, a cost-benefit analysis of using
      bike/pedestrian trails in Lincoln, Nebraska, to reduce health care costs
      associated with inactivity was conducted. Data was obtained from the city's 1998
      Recreational Trails Census Report and the literature. Per capita annual cost of
      using the trails was 209.28 U.S. dollars (59.28 U.S. dollars construction and
      maintenance, 150 U.S. dollars of equipment and travel). Per capita annual direct
      medical benefit of using the trails was 564.41 U.S. dollars. The cost-benefit
      ratio was 2.94, which means that every 1 U.S. dollar investment in trails for
      physical activity led to 2.94 U.S. dollars in direct medical benefit. The
      sensitivity analyses indicated the ratios ranged from 1.65 to 13.40. Therefore,
      building trails is cost beneficial from a public health perspective. The most
      sensitive parameter affecting the cost-benefit ratios were equipment and travel
      costs; however, even for the highest cost, every 1 U.S. dollar investment in
      trails resulted in a greater return in direct medical benefit.

PMID- 15855288
TI  - Implementation of a family intervention to increase fruit and vegetable intake:
      the Hi5+ experience.
AB  - Family is an important, yet challenging, target for dietary intervention. This
      article describes the implementation of Hi5+, a family fruit and vegetable (FV)
      promotion program. Complementing a fourth-grade school curriculum, the seven
      weekly Family Fun Nites were at-home family meal sharing and game evenings. A
      sample of families (N = 575; 69% consented) from schools in a southeastern U.S.
      urban area received tailored intervention materials based on their FV attitudes
      and family interaction styles. A pyramidal organizational design, using peer
      leaders, facilitated 71% of families to complete all seven sessions, whereas 84%
      completed at least one session. Significant independent predictors of program
      completion were attending an introductory Kick-Off Nite, interactive family
      style, additional adults in the household, married parents, being African
      American, earning more than 60,000 dollars, and additional children in the
      household. Family-specific issues and initial program experience are important
      considerations for implementing a family intervention.

PMID- 15855289
TI  - Hi5+: systematic development of a family intervention to increase fruit and
      vegetable intake.
AB  - This article describes the development of a peer-led home-based intervention to
      increase fruit and vegetable (FV) intake and family interaction among fourth
      graders and their families. Hi5+ intervention content and delivery strategies
      were developed using two complementary processes: cognitive mapping (CM), a
      consumer-based approach to identifying salient issues, and intervention mapping
      (IM), a comprehensive planning model. Step 1 involved creating plans to guide the
      design, implementation, and evaluation of Hi5+. We delineated our performance
      objectives and then prioritized those determinants we felt were most salient and
      changeable. Step 2 involved selecting and utilizing cognitive and behavioral
      theory constructs to develop intervention methods and strategies. Step 3 involved
      designing and pilot testing the instructional materials and other intervention
      components. Step 4 entailed developing plans for program adoption and
      implementation, while the final step (Step 5) involved creating a comprehensive
      evaluation plan. Implications of this multistep approach to intervention
      development are discussed.

PMID- 15855290
TI  - Under the influence: taking alcohol issues into the college classroom.
AB  - Alcohol use and abuse among college students pose an enormous and unique public
      health problem that is associated with significant harm to students. Colleges
      nationwide are seeking to address student alcohol use through a variety of
      programs and policies. An effort at Georgetown University in Washington, D.C.,
      combines a campus-wide dialogue on the subject with the infusion of alcohol
      issues into the curriculum of an undergraduate course in the School of Nursing
      and Health Studies. Course evaluations indicate that participants benefited from
      the curriculum infusion approach. Participants became aware of the health
      education resources available to students and the campus culture contributing to
      alcohol. In addition, student participants evaluated their own alcohol use, with
      significant modifications of alcohol consumption behaviors.

PMID- 15855291
TI  - Advice from bereaved parents: on forming partnerships for injury prevention.
AB  - We set out to learn whether, and how, parents of children who were fatally
      injured want to collaborate with injury prevention professionals. In this
      exploratory study, interviews were conducted with parents who had been identified
      through medical examiner files. Only a small minority of those we contacted chose
      to participate. The six mothers and five fathers who did felt that survivors
      should be offered such opportunities. They suggested waiting, however, at least a
      year before approaching parents. Our interviewees endorsed medical examiner's
      offices, health care providers, and police as legitimate avenues for identifying
      potential partners. They suggested that contact should first be made by mail.
      Professionals were encouraged to be sensitive, responsive, and realistic
      regarding the limits of our science. From a practical perspective, safety
      experts' contacts and political savvy appealed to respondents. Parents also
      expressed the need for coaching, and gentle understanding of the pain they live
      with every day.

PMID- 15855292
TI  - The role of local government in physical activity: employee perceptions.
AB  - A key component in the promotion of health-related physical activity at the
      community level is the formation of key partnerships with traditional and
      nontraditional providers of physical activity. Local government, in particular,
      has a significant investment in the health and well-being of the community
      through their contribution to the development of infrastructure and the build
      environment. However, local government perceptions of how this investment,
      commitment, and partnership translate to the promotion of physical activity is
      less known. To identify the role and perceptions of local government in the
      promotion of physical activity, a series of focus groups were conducted within
      six key departments of the Rockhampton City Council. The findings show that
      although physical activity is not considered the core business of local
      government, there was a clear understanding of the role that local government has
      in the provision of facilities and infrastructure that support that community's
      ability to be active. The focus groups identified emerging patterns concerning
      physical infrastructure, liability and safety, responsibility within the
      organizational structure, and community partnerships. These results inform
      physical activity community initiatives and enhance future collaboration between
      the community and local government in Rockhampton.

PMID- 15855293
TI  - Developmental stages in public health partnerships: a practical perspective.
AB  - Health education practitioners often form and provide support to partnerships
      directed toward public health goals. The authors viewed the start-up of a state
      health department/multiuniversity partnership for the evaluation of the state's
      tobacco settlement pilot project using the lens of the Tuckman four-stage model
      of group development. The four stages--forming, storming, norming, and performing
      -occurred in sequence but with pronounced overlap. Two types of performing-
      institutional and group performing--were observed. An awareness of group
      developmental stages can allow leaders and members to improve the ways their
      partnership works together. Applying Tuckman's model also can allow expectations
      about the group's progress and members' interactions to be managed so that tasks
      are aligned with the appropriate stage of development. Finally, for partnerships
      that have a long life span, understanding that the stages may occur several times
      throughout the group's existence can acclimate members to shifting
      responsibilities and relationships over time.

PMID- 15855294
TI  - Understanding cellular signaling pathways and their relationship to genotype and
      phenotype of muscle disease.

PMID- 15855295
TI  - Anticancer effect of an alpha-TEA liposome aerosol.

PMID- 15855296
TI  - IGF-1 in the brain as a regulator of reproductive neuroendocrine function.
AB  - Given the close relationship among neuroendocrine systems, it is likely that
      there may be common signals that coordinate the acquisition of adult reproductive
      function with other homeostatic processes. In this review, we focus on central
      nervous system insulin-like growth factor-1 (IGF-1) as a signal controlling
      reproductive function, with possible links to somatic growth, particularly during
      puberty. In vertebrates, the appropriate neurosecretion of the decapeptide
      gonadotropin-releasing hormone (GnRH) plays a critical role in the progression of
      puberty. Gonadotropin-releasing hormone is released in pulses from neuroterminals
      in the median eminence (ME), and each GnRH pulse triggers the production of the
      gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
      These pituitary hormones in turn stimulate the synthesis and release of sex
      steroids by the gonads. Any factor that affects GnRH or gonadotropin pulsatility
      is important for puberty and reproductive function and, among these factors, the
      neurotrophic factor IGF-1 is a strong candidate. Although IGF-1 is most commonly
      studied as the tertiary peripheral hormone in the somatotropic axis via its
      synthesis in the liver, IGF-1 is also synthesized in the brain, within neurons
      and glia. In neuroendocrine brain regions, central IGF-1 plays roles in the
      regulation of neuroendocrine functions, including direct actions on GnRH neurons.
      Moreover, GnRH neurons themselves co-express IGF-1 and the IGF-1 receptor, and
      this expression is developmentally regulated. Here, we examine the role of IGF-1
      acting in the hypothalamus as a critical link between reproductive and other
      neuroendocrine functions.

PMID- 15855297
TI  - Molecular machinery and mechanism of cell secretion.
AB  - Secretion occurs in all living cells and involves the delivery of intracellular
      products to the cell exterior. Secretory products are packaged and stored in
      membranous sacs or vesicles within the cell. When the cell needs to secrete these
      products, the secretory vesicles containing them dock and fuse at plasma membrane
      associated supramolecular structures, called porosomes, to release their
      contents. Specialized cells for neurotransmission, enzyme secretion, or hormone
      release use a highly regulated secretory process. Similar to other fundamental
      cellular processes, cell secretion is precisely regulated. During secretion,
      swelling of secretory vesicles results in a build-up of intravesicular pressure,
      allowing expulsion of vesicular contents. The extent of vesicle swelling dictates
      the amount of vesicular contents expelled. The discovery of the porosome as the
      universal secretory machinery, its isolation, its structure and dynamics at
      nanometer resolution and in real time, and its biochemical composition and
      functional reconstitution into artificial lipid membrane have been determined.
      The molecular mechanism of secretory vesicle swelling and the fusion of opposing
      bilayers, that is, the fusion of secretory vesicle membrane at the base of the
      porosome membrane, have also been resolved. These findings reveal, for the first
      time, the universal molecular machinery and mechanism of secretion in cells.

PMID- 15855298
TI  - Repletion of copper-deficient rats with dietary copper restores duodenal
      hephaestin protein and iron absorption.
AB  - Copper (Cu) deficiency in rats reduces the relative concentration of duodenal
      hephaestin (Hp), reduces iron (Fe) absorption, and causes anemia. An experiment
      was conducted to determine whether these effects could be reversed by dietary Cu
      repletion. Five groups of eight weanling male rats each were used. Group 1 was
      fed a Cu-adequate diet (5.0 mg Cu/kg; CuA) and Group 2 was fed a Cu-deficient
      diet (0.25 mg Cu/kg; CuD) for 28 days. The rats were fed 1.0 g each of their
      respective diets labeled with 59Fe (37 kBq/g), and the amount of label retained
      was measured one week later by whole-body-counting (WBC). Group 3 was fed a CuA
      diet and Groups 4 and 5 were fed a CuD diet for 28 days. Group 5 was then fed the
      CuA diet for another week while Groups 3 and 4 continued on their previous
      regimens. Rats in Groups 3, 4, and 5 were fed 1.0 g of diet labeled with 59Fe,
      and the amount of label retained was measured by WBC one week later. Rats were
      killed and duodenal enterocytes isolated for Hp protein analysis, whole blood was
      analyzed for hematological parameters, and various organs for 59Fe content. CuD
      rats absorbed less (P<0.05) Fe than CuA rats, the relative amount of duodenal Hp
      was less (P<0.05) in CuD rats, and the CuD rats developed anemia. After the CuD
      rats had been repleted with Cu for one week, Fe retention rose to values even
      higher (P<0.05) than those in CuA rats. After two weeks, the relative amount of
      duodenal Hp was higher (P<0.05) than normal, and most signs of anemia were
      reversed. Liver 59Fe was elevated in CuD rats, but was restored to normal upon Cu
      repletion. These findings suggest a strong association between duodenal Hp
      abundance and Fe absorption in the CuD rat, and that reduced Fe absorption is an
      important factor in the cause of anemia.

PMID- 15855299
TI  - Phytoestrogens modulate prostaglandin production in bovine endometrium: cell type
      specificity and intracellular mechanisms.
AB  - Prostaglandins (PGs) are known to modulate the proper cyclicity of bovine
      reproductive organs. The main luteolytic agent in ruminants is PGF2alpha, whereas
      PGE2 has luteotropic actions. Estradiol 17beta (E2) regulates uterus function by
      influencing PG synthesis. Phytoestrogens structurally resemble E2 and possess
      estrogenic activity; therefore, they may mimic the effects of E2 on PG synthesis
      and influence the reproductive system. Using a cell-culture system of bovine
      epithelial and stromal cells, we determined cell-specific effects of
      phytoestrogens (i.e., daidzein, genistein), their metabolites (i.e., equol and
      para-ethyl-phenol, respectively), and E2 on PGF2alpha and PGE2 synthesis and
      examined the intracellular mechanisms of their actions. Both PGs produced by
      stromal and epithelial cells were significantly stimulated by phytoestrogens and
      their metabolites. However, PGF2alpha synthesis by both kinds of cells was
      greater stimulated than PGE2 synthesis. Moreover, epithelial cells treated with
      phytoestrogens synthesized more PGF2alpha than stromal cells, increasing the
      PGF2alpha to PGE2 ratio. The epithelial and stromal cells were preincubated with
      an estrogen-receptor (ER) antagonist (i.e., ICI), a translation inhibitor (i.e.,
      actinomycin D), a protein kinase A inhibitor (i.e., staurosporin), and a
      phospholipase C inhibitor (i.e., U73122) for 0.5 hrs and then stimulated with
      equol, para-ethyl-phenol, or E2. Although the action of E2 on PGF2alpha synthesis
      was blocked by all reagents, the stimulatory effect of phytoestrogens was blocked
      only by ICI and actinomycin D in both cell types. Moreover, in contrast to E2
      action, phytoestrogens did not cause intracellular calcium mobilization in either
      epithelial or stromal cells. Phytoestrogens stimulate both PGF2alpha and PGE2 in
      both cell types of bovine endometrium via an ER-dependent genomic pathway.
      However, because phytoestrogens preferentially stimulated PGF2alpha synthesis in
      epithelial cells of bovine endometrium, they may disrupt uterus function by
      altering the PGF2alpha to PGE2 ratio.

PMID- 15855300
TI  - Hypothalamic neuronal histamine modulates febrile response but not anorexia
      induced by lipopolysaccharide.
AB  - This study examined the contribution of hypothalamic neuronal histamine (HA) to
      the anorectic and febrile responses induced by lipopolysaccharide (LPS), an
      exogenous pyrogen, and the endogenous pyrogens interleukin-1beta (IL-1beta) and
      tumor necrosis factor-alpha (TNF-alpha). Intraperitoneal (ip) injection of LPS,
      IL-1beta, or TNF-alpha suppressed 24-hr cumulative food intake and increased
      rectal temperature in rats. To analyze the histaminergic contribution, rats were
      pretreated with intracerebroventricular (icv) injection of 2.44 mmol/kg or ip
      injection of 244 mmol/kg of alpha-fluoromethylhistidine (FMH), a suicide
      inhibitor of histidine decarboxylase (HDC), to deplete neural HA. The depletion
      of neural HA augmented the febrile response to ip injection of LPS and IL-1beta
      and alleviated the anorectic response to ip injection of IL-1beta. However, the
      depletion of neural HA did not modify the LPS-induced anorectic response or TNF
      alpha-induced febrile and anorectic responses. Consistent with these results, the
      rate of hypothalamic HA turnover, assessed by the accumulation of tele
      methylhistamine (t-MH), was elevated with ip injections of LPS and IL-1beta, but
      unaffected by TNF-alpha at equivalent doses. This suggests that (i) LPS and IL
      1beta activate hypothalamic neural HA turnover; (ii) hypothalamic neural HA
      suppresses the LPS- and IL-1beta-induced febrile responses and accelerates the IL
      1beta-induced anorectic response; and (iii) TNF-alpha modulates the febrile and
      anorectic responses via a neural HA-independent pathway. Therefore, hypothalamic
      neural HA is involved in the IL-1beta-dominant pathway, rather than the TNF-alpha
      dominant pathway, preceding the systemic inflammatory response induced by
      exogenous pyrogens, such as LPS. Further research on this is needed.

PMID- 15855301
TI  - Sensitive detection of prion protein in human urine.
AB  - Transmissible spongiform encephalopathies are a group of infectious diseases
      typically associated with the accumulation of a protease-resistant and beta-sheet
      rich prion protein, PrPSc, in affected brains. PrPSc is an altered isoform
      derived from the host-encoded glycoprotein, PrPC. The expression of PrPC is the
      highest in brain tissue, but it can also be detected at low levels in peripheral
      tissue. However, it is unclear whether a significant amount of PrPC is released
      into body fluid and excreted into urine. We have developed a simple, rapid method
      for the reliable detection of PrPC in urine from normal subjects by Western
      blotting. Our method can easily and reliably detect PrPC in apparently healthy
      individuals using less than 1 ml of urine in which the amount of urinary PrPC is
      estimated to be in the range of low micrograms/liter.

PMID- 15855302
TI  - Plasmodium falciparum inhibitory capacities of paired maternal-cord sera from
      south-west province, Cameroon.
AB  - In malaria endemic areas, young children are protected against malaria attack
      during the first few weeks of life partially by transplacentally acquired
      antibodies. In this study, we show, using an in vitro assay, that part of these
      antibodies are involved with blocking the re-invasion of host red blood cells by
      erythrocytic merozoites. One hundred consecutive paired maternal-cord blood
      samples were collected at delivery and their plasma assayed for total IgG
      antibodies against crude blood stage antigens by the ELISA. The Ig fraction were
      precipitated from the plasma samples with (NH(4))(2)SO(4), purified on PD10
      columns and used in vitro in determining the re-invasion inhibitory capacities.
      The mean (+/-SD) ELISA OD(405) IgG antibodies to crude blood stage antigens of
      maternal (0.476 +/- 0.48) and cord (0.421 +/- 0.39) plasma samples was not
      significantly different. However, the mean total protein concentration of the Ig
      fractions for maternal samples (15.82 +/- 3.85) was significantly higher
      (p=0.005) than that of paired cord samples (12.87 +/- 2.86 mg/ml). There was no
      correlation between anti-Plasmodium falciparum-specific IgG levels and total
      protein concentrations of the Ig fractions of both maternal and cord samples. The
      entire test Ig fractions were strongly inhibitory (>50 per cent) except for four
      paired maternal cord samples, which were moderately inhibitory (21--50 per cent)
      at the highest concentration tested (1:2 dilution). Furthermore, there was no
      correlation between maternal IgG levels and percentage re-invasion inhibition at
      the 1:2 dilution. The results suggest that mothers resident in malaria endemic
      areas possess naturally acquired re-invasion inhibitory antibodies and their
      foetuses can acquire these antibodies transplacentally, which may contribute to
      the relative protection observed in infants during their first few weeks of life.

PMID- 15855304
TI  - Normal values of pulse oximetry in newborns at high altitude.
AB  - The aim of the study was to establish normal values of pulse oximetry saturation,
      respiratory rate, heart rate, and blood pressure in healthy newborns at high
      altitude. Vital signs and oximetry saturation readings were collected from
      healthy term newborns at birth, at 1 h, and at 24 h of life. These were analyzed
      and compared with reference ranges at sea level. This study was carried out at
      altitudes of 1640 m above sea level in Taif city, Saudi Arabia. A total of 6011
      term newborns were examined at birth and 1 h and 4274 were examined at 24 h of
      life. At birth, the mean SpO(2) was 68.6 per cent and 60.3 per cent from the
      right upper and lower limbs, respectively. Mean SpO(2) was 94.3 per cent and 95.4
      per cent at the age of 1 and 24 h, respectively. These values were significantly
      lower than those reported at sea level. The mean respiratory rate, heart rate,
      and mean blood pressure at 24 h were 45.7/min, 149.7/min, and 46.9 mmHg,
      respectively. It is concluded that pulse oximetry saturation for newborn babies
      is lower at higher altitudes than at sea level. This effect is observable at
      altitudes of 1600 m above sea level. Cut-off levels lower than those used at sea
      level should be adopted when dealing with newborns living at high altitudes.

PMID- 15855303
TI  - Anti-tumour necrosis factor-alpha treatment of juvenile idiopathic arthritis in a
      patient with common variable immunodeficiency.

PMID- 15855305
TI  - Paradoxical appearance of intracranial tuberculoma in a child with tuberculous
      meningitis.
AB  - Intracranial tuberculomas are known to develop during treatment of tuberculous
      meningitis (TBM). However, they usually develop within weeks or a couple of
      months after the start of antituberculous therapy (ATT). We present a case of an
      18-month-old boy who developed tuberculomas after 9 months of ATT, which
      subsequently responded to the reintroduction of steroids. Thus, one must keep a
      watch for neurological deterioration in a child of TBM and if it is due to
      tuberculomas, one may have to continue steroids and ATT for a long time.

PMID- 15855306
TI  - Is there a relationship between childhood Helicobacter pylori infection and iron
      deficiency anemia?
AB  - An association between Helicobacter pylori infection and iron deficiency anemia
      has been reported in children, and it has been proposed that H. pylori infection
      needs to be eradicated to treat absolutely iron deficiency anemia (IDA). We
      investigated whether there was any correlation between H. pylori infection and
      iron deficiency (ID) and IDA in children, and whether the eradication of H.
      pylori infection without iron treatment would lead to the resolution of ID.
      Hemoglobin and ferritin levels, H. pylori stool antigen test and (14)C urea
      breath test were measured in 140 children aged 6--16 years (median 9.5 years).
      Children with H. pylori infection were divided into three groups on the basis of
      hemoglobin, mean corpuscular volume (MCV), and serum ferritin levels: groups of
      IDA, ID, and control. All the children received anti-H. pylori combination
      therapy consisting of amoxicillin, clarithromycin, and lansoprazole. Hemoglobin
      and MCV values rose significantly compared with baseline values after H. pylori
      eradication without iron supplementation in children with IDA (p=0.002 and
      p=0.003, respectively). Ferritin values increased significantly after H. pylori
      eradication in children with ID (p<0.001). We conclude that complete recovery of
      ID and IDA can be achieved with H. pylori eradication without iron
      supplementation in children with H. pylori infection.

PMID- 15855307
TI  - Rapid detection and clinical features of influenza and parainfluenza in infants
      and young children hospitalized with acute lower respiratory illnesses.
AB  - During the winter seasons of 2003 and 2004, a total of 282 nasopharyngeal
      aspirates (NPAs) were obtained from infants and young children admitted to the
      Buraidah Maternity and Pediatric Hospital, Al-Qassim, Saudi Arabia, and
      clinically diagnosed as suffering from acute lower respiratory tract infections.
      NPAs were screened for the presence of respiratory viruses and further confirmed
      for the presence of influenza, parainfluenza, and adenovirus using direct
      fluorescein-labeled monoclonal antibody assay. Of all the 282 specimens, 44 (15.6
      per cent) were found positive for influenza, parainfluenza, and adenovirus.
      Influenza A and B were identified in 22 (7.8 per cent), 4 (1.4 per cent),
      respectively, parainfluenza 1, 2, and 3 in 9 (3.2 per cent), 4 (1.4 per cent),
      and 1 (0.4 per cent), respectively, and adenovirus in 4 (1.4 per cent). Influenza
      and parainfluenza viruses were noted more in patients below the age of 1 year;
      11.3 per cent and 6.2 per cent, respectively. Bronchiolitis, coughing, and
      tachpnea were significantly more frequent in infants with influenza infection:
      13.1 per cent, 55 per cent, and 50 per cent, respectively. The availability of
      rapid viral diagnostic assay is an important tool for physicians to make more
      accurate treatment decisions and therefore reduces unnecessary antibiotic usage
      and hospital stay for patients.

PMID- 15855308
TI  - ADA Outstanding Scientific Achievement Lecture 2004. Thirty years of
      investigating the autoimmune basis for type 1 diabetes: why can't we prevent or
      reverse this disease?
AB  - Thirty years ago, a convergence of investigational observations lead to the now
      widely accepted notion that type 1 diabetes results from an autoimmune
      destruction of insulin-producing beta-cells in subjects genetically predisposed
      to the disease. Improvements in understanding of the natural history of type 1
      diabetes, the biochemical identification of autoantigens, the discovery of
      spontaneous animal models for the disease, the availability of immune-modulating
      agents, and other important facets, including disease prediction, drove an early
      sense of optimism that the prevention of type 1 diabetes was possible and, in
      some research circles, that ability was thought to be within a not-to-distant
      reach. Unfortunately, those early expectations proved overly optimistic, and
      despite the aforementioned knowledge gains, the generation of improved
      investigational tools, the identification of methods to prevent the disease in
      animal models, and the formation of very large disease prevention trials, a means
      to prevent type 1 diabetes in humans continues to remain elusive. Believing in
      the concept of "informative failures" (a.k.a., wise people learn from their
      mistakes), this lecture reviews the knowledge base collected over this time
      period and, when combined with an analysis of those research experiences, sets
      forth a proposal for future investigations that will, hopefully, turn discoveries
      into a means for the prevention or reversal of type 1 diabetes.

PMID- 15855309
TI  - Insulin signaling in the central nervous system: a critical role in metabolic
      homeostasis and disease from C. elegans to humans.
AB  - Insulin and its signaling systems are implicated in both central and peripheral
      mechanisms governing the ingestion, distribution, metabolism, and storage of
      nutrients in organisms ranging from worms to humans. Input from the environment
      regarding the availability and type of nutrients is sensed and integrated with
      humoral information (provided in part by insulin) regarding the sufficiency of
      body fat stores. In response to these afferent inputs, neuronal pathways are
      activated that influence energy flux and nutrient metabolism in the body and
      ensure reproductive competency. Growing evidence supports the hypothesis that
      reduced central nervous system insulin signaling from either defective secretion
      or action contributes to the pathogenesis of common metabolic disorders,
      including diabetes and obesity, and may therefore help to explain the close
      association between these two disorders. These considerations implicate insulin
      action in the brain, an organ previously considered to be insulin independent, as
      a key determinant of both glucose and energy homeostasis.

PMID- 15855310
TI  - Glycogen synthesis in human gastrocnemius muscle is not representative of whole
      body muscle glycogen synthesis.
AB  - The introduction of 13C magnetic resonance spectroscopy (MRS) has enabled
      noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based
      on measurements by the MRS technique assume that glucose metabolism in
      gastrocnemius muscle is representative for all skeletal muscles and thus can be
      extrapolated to whole-body muscle glucose metabolism. An alternative method to
      assess whole-body muscle glycogen synthesis is the use of [3-(3)H]glucose. In the
      present study, we compared this method to the MRS technique, which is a well
      validated technique for measuring muscle glycogen synthesis. Muscle glycogen
      synthesis was measured in the gastrocnemius muscle of six lean healthy subjects
      by MRS and by the isotope method during a hyperinsulinemic-euglycemic clamp. Mean
      muscle glycogen synthesis as measured by the isotope method was 115 +/- 26
      micromol x kg(-1) muscle x min(-1) vs. 178 +/- 72 micromol x kg(-1) muscle x min(
      1) (P = 0.03) measured by MRS. Glycogen synthesis rates measured by MRS exceeded
      100% of glucose uptake in three of the six subjects. We conclude that glycogen
      synthesis rates measured in gastrocnemius muscle cannot be extrapolated to whole
      body muscle glycogen synthesis.

PMID- 15855311
TI  - Proteome analysis of skeletal muscle from obese and morbidly obese women.
AB  - Obesity-related diseases such as the metabolic syndrome and type 2 diabetes
      originate, in part, from the progressive metabolic deterioration of skeletal
      muscle. A preliminary proteomic survey of rectus abdominus muscle detected a
      statistically significant increase in adenylate kinase (AK)1, glyceraldehyde-3
      phosphate dehydrogenase (GAPDH), and aldolase A in obese/overweight and morbidly
      obese women relative to lean control subjects. AK1 is essential for the
      maintenance of cellular energy charge, and GAPDH and aldolase A are well known
      glycolytic enzymes. We found that muscle AK1 protein and enzymatic activity
      increased 2.9 and 90%, respectively, in obese women and 9.25 and 100%,
      respectively, in morbidly obese women. The total enzymatic activity of creatine
      kinase, which also regulates energy metabolism in muscle, was shown to increase
      30% in obese/overweight women only. We propose that increased protein and
      enzymatic activity of AK1 is representative of a compensatory glycolytic drift to
      counteract reduced muscle mitochondrial function with the progression of obesity.
      This hypothesis is supported by increased abundance of the glycolytic enzymes
      GAPDH and aldolase A in obese and morbidly obese muscle. In summary, proteome
      analysis of muscle has helped us better describe the molecular etiology of
      obesity-related disease.

PMID- 15855312
TI  - Impact of genetic versus environmental factors on the control of muscle glycogen
      synthase activation in twins.
AB  - Storage of glucose as glycogen accounts for the largest proportion of muscle
      glucose metabolism during insulin infusion in normal and insulin-resistant
      subjects. Studies in first-degree relatives have indicated a genetic origin of
      the defective insulin activation of muscle glycogen synthase (GS) in type 2
      diabetes. The aim of this study was to evaluate the relative impact of genetic
      versus nongenetic factors on muscle GS activation and regulation in young and
      elderly twins examined with a 2-h euglycemic-hyperinsulinemic (40 mU x m(-2) x
      min(-1)) clamp combined with indirect calorimetry and excision of muscle
      biopsies. The etiological components were determined using structural equation
      modeling. Fractional GS activity; GS phosphorylation at sites 2, 2 + 2a, and 3a +
      3b corrected for total GS protein; and GS kinase 3 (GSK3) activity were similar
      in both age groups, whereas total GS activity and protein were lower in elderly
      compared with younger twins. GS fractional activity increased significantly
      during insulin stimulation in both young and elderly twins. Conversely, there was
      a significant decrease in GS phosphorylation at site 3a + 3b and GSK3 activity
      during insulin stimulation in both age groups, whereas GS phosphorylation at site
      2 and 2 + 2a only decreased on insulin stimulation in the younger twins. The
      increment in whole-body glucose disposal (Rd) and nonoxidative glucose metabolism
      (insulin - basal) correlated significantly with the increment in GS fractional
      activity. Fractional GS activity had a major environmental component in both age
      groups. GSK3 activity exhibited a genetic component in young (basal: a2 = 0.42;
      insulin: a2 = 0.58) and elderly (insulin: a2 = 0.56) twins. Furthermore, GS
      phosphorylation at site 2 (insulin: a2 = 0.69) in the elderly and at site 3a + 3b
      (insulin: a2 = 0.50) in the young twins had a genetic component. In conclusion,
      GSK3 activity and GS phosphorylation, particularly at sites 2 and 3a + 3b, had
      major genetic components. Total and fractional GS activities per se were, on the
      other hand, predominantly controlled by environmental factors. Moreover, GS
      activity was intact with increasing age, despite a significant reduction in
      nonoxidative glucose metabolism.

PMID- 15855313
TI  - Oscillations of fatty acid and glycerol release from human subcutaneous adipose
      tissue in vivo.
AB  - We sought evidence for pulsatility of lipolysis in human subcutaneous adipose
      tissue in vivo. Arterialized and adipose tissue venous blood samples were drawn
      at 2-min intervals from nine healthy subjects. This procedure was repeated during
      hyperinsulinemic-euglycemic clamp to remove insulin pulsatility. We found
      evidence for pulsatile release of both nonesterified fatty acids (NEFAs) (seven
      of nine subjects) and glycerol (five of six subjects) with a period of
      approximately 12-14 min. This pulsatility was maintained even during the
      hyperinsulinemic clamp. Checks were made for spurious pulse detection, including
      the creation of "mock" venoarterialized differences by subtracting one subject's
      arterialized concentrations from another's venous; the peaks detected were less
      consistent in character than with real data (peak width, P = 0.006; peak
      interval, P < 0.004). Significant cross-correlations between NEFA and glycerol
      release also provided evidence of a real effect. Arterialized norepinephrine
      concentrations were also pulsatile, but the period did not match that of NEFA and
      glycerol release. Insulin concentrations were pulsatile with a typical period of
      12 min, but this was not significantly cross-correlated with lipolysis. We
      conclude that release from adipose tissue of the products of lipolysis is
      pulsatile in humans.

PMID- 15855314
TI  - Adenovirus-mediated adiponectin expression augments skeletal muscle insulin
      sensitivity in male Wistar rats.
AB  - In this study, we investigated the chronic in vivo effect of adiponectin on
      insulin sensitivity and glucose metabolism by overexpressing the adiponectin
      protein in male Wistar rats using intravenous administration of an adenovirus
      (Adv-Adipo). Virally infected liver secreted adiponectin as high and low
      molecular weight complexes. After 7 days of physiological or supraphysiological
      hyperadiponectinemia, the animals displayed enhanced insulin sensitivity during
      the glucose tolerance and insulin tolerance tests. Glucose clamp studies
      performed at submaximal and maximal insulin infusion rates (4 and 25 mU x kg(-1)
      x min(-1), respectively) also demonstrated increased insulin sensitivity in Adv
      Adipo animals, with the insulin-stimulated glucose disposal rate being increased
      by 20-67%. In contrast, insulin's effect on the suppression of hepatic glucose
      output and plasma free fatty acid levels was not enhanced in Adv-Adipo rats
      compared with controls, suggesting that high levels of adiponectin expression in
      the liver may lead to a local desensitization. Consistent with the clamp data,
      the activation of AMP-activated protein kinase was significantly enhanced in
      skeletal muscle (by 50%) but not in liver. One interesting finding was that in
      male Wistar rats, both AdipoR1 and AdipoR2 expression levels were higher in
      skeletal muscle than in liver, as it is the case in humans. These results
      indicate that chronic adiponectin treatment enhances insulin sensitivity and
      could serve as a therapy for human insulin resistance.

PMID- 15855315
TI  - Effects of diet and genetic background on sterol regulatory element-binding
      protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic
      syndrome.
AB  - Both environmental and genetic factors play important roles in the development of
      the metabolic syndrome. To elucidate how these factors interact under normal
      conditions, C57Bl/6 (B6) and 129S6/SvEvTac (129) mice were placed on a low-fat or
      high-fat diet. Over 18 weeks, the 129 strain developed features of the metabolic
      syndrome, notably obesity, hyperinsulinemia, and glucose intolerance only on the
      high-fat diet; the B6 strain on the other hand developed these features on both
      diets. High-fat feeding of both strains led to decreased serum triglycerides,
      hepatic steatosis, and hypercholesterolemia; however, B6 mice developed worse
      steatosis and a larger increase in LDL cholesterol. Both B6 background and high
      fat feeding increased sterol regulatory element-binding protein-1c (SREBP-1c), a
      key regulator of lipogenic gene transcription, and its downstream targets.
      Stearoyl-CoA desaturase 1 (SCD1), an enzyme that regulates monounsaturated fatty
      acid (MUFA) synthesis, was also increased at the mRNA and enzyme activity levels
      by both high-fat feeding and B6 background. Furthermore, lipid analysis revealed
      increased hepatic triglycerides and MUFAs in B6 and high-fat-fed mice. Thus,
      dietary fat and genetic background act through SREBP-1c and SCD1 to affect
      hepatic lipid metabolism contributing to the development of the metabolic
      syndrome.

PMID- 15855316
TI  - Parasympathetic innervation and function of endocrine pancreas requires the glial
      cell line-derived factor family receptor alpha2 (GFRalpha2).
AB  - Vagal parasympathetic input to the islets of Langerhans is a regulator of islet
      hormone secretion, but factors promoting parasympathetic islet innervation are
      unknown. Neurturin signaling via glial cell line-derived neurotrophic factor
      family receptor alpha2 (GFRalpha2) has been demonstrated to be essential for the
      development of subsets of parasympathetic and enteric neurons. Here, we show that
      the parasympathetic nerve fibers and glial cells within and around the islets
      express GFRalpha2 and that islet parasympathetic innervation in GFRalpha2
      knockout (KO) mice is reduced profoundly. In wild-type mice, neuroglucopenic
      stress produced a robust increase in plasma levels of islet hormones. In the
      GFRalpha2-KO mice, however, pancreatic polypeptide and insulin responses were
      completely lost and glucagon response was markedly impaired. Islet morphology and
      sympathetic innervation, as well as basal secretions of the islet hormones, were
      unaffected. Moreover, a glucose tolerance test failed to reveal differences
      between the genotypes, indicating that direct glucose-stimulated insulin
      secretion was not affected by GFRalpha2 deficiency. These results show that
      GFRalpha2 signaling is needed for development of the parasympathetic islet
      innervation that is critical for vagally induced hormone secretion. The GFRalpha2
      KO mouse represents a useful model to study the role of parasympathetic
      innervation of the endocrine pancreas in glucose homeostasis.

PMID- 15855317
TI  - Short-term overexpression of a constitutively active form of AMP-activated
      protein kinase in the liver leads to mild hypoglycemia and fatty liver.
AB  - AMP-activated protein kinase (AMPK) is a major therapeutic target for the
      treatment of diabetes. We investigated the effect of a short-term overexpression
      of AMPK specifically in the liver by adenovirus-mediated transfer of a gene
      encoding a constitutively active form of AMPKalpha2 (AMPKalpha2-CA). Hepatic
      AMPKalpha2-CA expression significantly decreased blood glucose levels and
      gluconeogenic gene expression. Hepatic expression of AMPKalpha2-CA in
      streptozotocin-induced and ob/ob diabetic mice abolished hyperglycemia and
      decreased gluconeogenic gene expression. In normal mouse liver, AMPKalpha2-CA
      considerably decreased the refeeding-induced transcriptional activation of genes
      encoding proteins involved in glycolysis and lipogenesis and their upstream
      regulators, SREBP-1 (sterol regulatory element-binding protein-1) and ChREBP
      (carbohydrate response element-binding protein). This resulted in decreases in
      hepatic glycogen synthesis and circulating lipid levels. Surprisingly, despite
      the inhibition of hepatic lipogenesis, expression of AMPKalpha2-CA led to fatty
      liver due to the accumulation of lipids released from adipose tissue. The
      relative scarcity of glucose due to AMPKalpha2-CA expression led to an increase
      in hepatic fatty acid oxidation and ketone bodies production as an alternative
      source of energy for peripheral tissues. Thus, short-term AMPK activation in the
      liver reduces blood glucose levels and results in a switch from glucose to fatty
      acid utilization to supply energy needs.

PMID- 15855318
TI  - A role for iNOS in fasting hyperglycemia and impaired insulin signaling in the
      liver of obese diabetic mice.
AB  - Chronic inflammation has been postulated to play an important role in the
      pathogenesis of insulin resistance. Inducible nitric oxide synthase (iNOS) has
      been implicated in many human diseases associated with inflammation. iNOS
      deficiency was shown to prevent high-fat diet-induced insulin resistance in
      skeletal muscle but not in the liver. A role for iNOS in fasting hyperglycemia
      and hepatic insulin resistance, however, remains to be investigated in obesity
      related diabetes. To address this issue, we examined the effects of a specific
      inhibitor for iNOS, L-NIL, in obese diabetic (ob/ob) mice. iNOS expression was
      increased in the liver of ob/ob mice compared with wild-type mice. Treatment with
      iNOS inhibitor reversed fasting hyperglycemia with concomitant amelioration of
      hyperinsulinemia and improved insulin sensitivity in ob/ob mice. iNOS inhibitor
      also increased the protein expression of insulin receptor substrate (IRS)-1 and 
      2 1.5- and 2-fold, respectively, and enhanced IRS-1- and IRS-2-mediated insulin
      signaling in the liver of ob/ob mice. Exposure to NO donor and ectopically
      expressed iNOS decreased the protein expression of IRS-1 and -2 in cultured
      hepatocytes. These results suggest that iNOS plays a role in fasting
      hyperglycemia and contributes to hepatic insulin resistance in ob/ob mice.

PMID- 15855319
TI  - Akt2 is essential for the full effect of calorie restriction on insulin
      stimulated glucose uptake in skeletal muscle.
AB  - Brief calorie restriction (CR; 20 days of 60% of ad libitum [AL] intake) improves
      insulin-stimulated glucose transport, concomitant with enhanced phosphorylation
      of Akt2. The purpose of this study was to determine whether Akt2 is essential for
      the calorie restriction-induced enhancement in skeletal muscle insulin
      sensitivity. We measured insulin-stimulated 2-deoxyglucose (2DG) uptake in
      isolated extensor digitorum longus (EDL) and soleus muscles from male and female
      wild-type (WT) and Akt2-null (knockout [KO]) mice after ad libitum or calorie
      restricted (20 days at 60% of AL) feeding. In WT mice, calorie restriction
      significantly enhanced insulin-stimulated 2DG uptake in both muscles regardless
      of sex. However, in KO mice, calorie restriction did not enhance insulin
      stimulated 2DG in male or female EDL or in female soleus. Only in male KO soleus
      did calorie restriction significantly increase insulin-stimulated 2DG through an
      Akt2-independent mechanism, although 2DG uptake of the KO-CR group was reduced
      compared with the WT-CR soleus group. Akt2 serine phosphorylation was enhanced
      approximately two- to threefold in insulin-stimulated WT-CR versus WT-AL muscles.
      Calorie restriction induced an approximately 1.5- to 2-fold elevation in Akt1
      phosphorylation of insulin-treated muscles, regardless of genotype, but this
      increase was insufficient to replace Akt2 for insulin-stimulated 2DG in Akt2
      deficient muscles. These results indicate that Akt2 is essential for the full
      effect of brief calorie restriction on insulin-stimulated glucose uptake in
      skeletal muscle with physiologic insulin.

PMID- 15855320
TI  - Essential role of chicken ovalbumin upstream promoter-transcription factor II in
      insulin secretion and insulin sensitivity revealed by conditional gene knockout.
AB  - Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) has been
      implicated in the control of blood glucose by its potent effect on expression and
      signaling of various nuclear receptors. To understand the role of COUP-TFII in
      glucose homeostasis, conditional COUP-TFII-deficient mice were generated and
      crossed with mice expressing Cre under the control of rat insulin II gene
      promoter, resulting in deletion of COUP-TFII in pancreatic beta-cells. Homozygous
      mutants died before birth for yet undetermined reasons. Heterozygous mice
      appeared healthy at birth and showed normal growth and fertility. When challenged
      intraperitoneally, the animals had glucose intolerance associated with reduced
      glucose-stimulated insulin secretion. Moreover, these heterozygous mice presented
      a mild increase in fasting and random-fed circulating insulin levels. In
      accordance, islets isolated from these animals exhibited higher insulin secretion
      in low glucose conditions and markedly decreased glucose-stimulated insulin
      secretion. Their pancreata presented normal microscopic architecture and insulin
      content up to 16 weeks of study. Altered insulin secretion was associated with
      peripheral insulin resistance in whole animals. It can be concluded that COUP
      TFII is a new, important regulator of glucose homeostasis and insulin
      sensitivity.

PMID- 15855321
TI  - The contribution of visceral adipose tissue to splanchnic cortisol production in
      healthy humans.
AB  - Cortisol is regenerated from cortisone by 11beta-hydroxysteroid dehydrogenase
      type 1 (11HSD1), amplifying glucocorticoid action in adipose tissue and liver.
      11HSD1 inhibitors are being developed for type 2 diabetes and may be most
      effective in obesity, where adipose 11HSD1 is increased. However, the magnitude
      of regeneration of cortisol in different tissues in humans is unknown, hindering
      understanding of the pathophysiological and therapeutic importance of 11HSD1. In
      eight healthy men, we infused 9,11,12,12-(2)H4-cortisol and measured tracer
      enrichment in the hepatic vein as an indicator of total splanchnic cortisol
      generation. Oral cortisone (25 mg) was then given to measure first-pass hepatic
      cortisol generation. In steady state, splanchnic cortisol production was 45 +/-
      11 nmol/min when arterialized plasma cortisone concentration was 92 +/- 7 nmol/l.
      Extrapolation from hepatic cortisol generation after oral cortisone suggested
      that, at steady state, the liver contributes 15.2 nmol/min and extrahepatic
      splanchnic tissue contributes 29.8 nmol/min to the total splanchnic cortisol
      production. We conclude that tissues draining into the portal vein, including
      visceral adipose tissue, contribute substantially to the regeneration of
      cortisol. Thus, in addition to free fatty acids and adipokines, the portal vein
      delivers cortisol to the liver, and inhibition of 11HSD1 in visceral adipose
      tissue may indeed be valuable in ameliorating insulin resistance in obesity.

PMID- 15855322
TI  - Differential association of basal and postprandial plasma ghrelin with leptin,
      insulin, and type 2 diabetes.
AB  - To gain further insight into the regulatory role of insulin and leptin on plasma
      ghrelin, 56 normal weight, 128 normoinsulinemic obese, 121 hyperinsulinemic
      obese, and 30 type 2 diabetic normoinsulinemic and 75 type 2 diabetic
      hyperinsulinemic obese patients were examined. In the obese subjects, basal
      hyperinsulinemia was associated with significantly lower ghrelin independent of
      BMI, age, and leptin. In normoinsulinemic (normal weight and normoinsulinemic
      obese) subjects, ghrelin was inversely related to stepwise increasing leptin.
      Multiple regression analysis and matching for insulin revealed a significant
      negative interaction of ghrelin with leptin but not insulin. In type 2 diabetic
      normoinsulinemic subjects, ghrelin was significantly lower compared with that in
      normoinsulinemic obese subjects. In type 2 diabetic hyperinsulinemic subjects,
      ghrelin was significantly lower than in normoinsulinemic subjects, whereas no
      further reduction was observed compared with hyperinsulinemic obese subjects. The
      postprandial decrease was significantly attenuated in normoinsulinemic obese and
      hyperinsulinemic obese subjects (-214.8 +/- 247 pg/ml [normal weight], -137.6 +/-
      107 pg/ml [normoinsulinemic obese], -85.5 +/- 69 pg/ml [hyperinsulinemic obese],
      P < 0.001; mean +/- SD), whereas type 2 diabetes had no independent postprandial
      effect. In conclusion, the present data support the concept that leptin could be
      of importance for suppression of basal ghrelin during moderate weight gain in
      normoinsulinemic subjects, whereas hyperinsulinemia but not leptin is responsible
      in more severe obesity. Postprandial suppression of ghrelin is attenuated by as
      yet unknown mechanisms that are related to body weight but not to insulin or type
      2 diabetes.

PMID- 15855323
TI  - Rosiglitazone increases indexes of stearoyl-CoA desaturase activity in humans:
      link to insulin sensitization and the role of dominant-negative mutation in
      peroxisome proliferator-activated receptor-gamma.
AB  - Fatty acid desaturases such as steaoryl-CoA desaturase (SCD) convert saturated to
      unsaturated fatty acids and are involved in lipogenesis. Observational and animal
      data suggest that SCD-1 activity is related to insulin sensitivity. However, the
      effects of insulin-sensitizing drugs on SCD gene expression and desaturase
      activities are unknown in humans. In a randomized, placebo-controlled, double
      blind, crossover study, 24 subjects with type 2 diabetes and one subject with
      partial lipodystrophy and diabetes due to dominant-negative mutation in the
      peroxisome proliferator-activated receptor-gamma (PPARgamma) gene (P467L)
      received placebo and rosiglitazone for 3 months. SCD gene expression in adipose
      tissue was determined in 23 subjects, and in a representative subgroup (n = 10)
      we assessed fatty acid composition in fasting plasma triglycerides to estimate
      SCD and delta6- and delta5-desaturase activity, using product-to-precursor
      indexes. SCD mRNA expression increased by 48% after rosiglitazone (P < 0.01). SCD
      and delta5-desaturase but not delta6-desaturase activity indexes were increased
      after rosiglitazone versus placebo (P < 0.01 and P < 0.05, respectively). The
      change in activity index but not the expression of SCD was associated with
      improved insulin sensitivity (r = 0.73, P < 0.05). In the P467L PPARgamma
      carrier, SCD and delta5-desaturase activity indexes were exceptionally low but
      were restored (52- and 15-fold increases, respectively) after rosiglitazone
      treatment. This study shows for the first time that rosiglitazone increases SCD
      activity indexes and gene expression in humans. An increased SCD activity index
      may reflect increased lipogenesis and might contribute to insulin sensitization
      by rosiglitazone. The restored SCD activity index after rosiglitazone in
      PPARgamma mutation supports a pivotal role of PPARgamma function in SCD
      regulation.

PMID- 15855324
TI  - Uncoupling protein 1 is necessary for norepinephrine-induced glucose utilization
      in brown adipose tissue.
AB  - Sympathetic stimulation activates glucose utilization in parallel with fatty acid
      oxidation and thermogenesis in brown adipose tissue (BAT) through the beta
      adrenergic receptors. To clarify the roles of the principal thermogenic molecule
      mitochondrial uncoupling protein 1 (UCP1) in the sympathetically stimulated
      glucose utilization, we investigated the uptake of 2-deoxyglucose (2-DG) into BAT
      and some other tissues of UCP1-knockout (KO) mice in vivo. In wild-type (WT)
      mice, administration of norepinephrine (NE) accelerated the disappearance of
      plasma 2-DG and increased 2-DG uptake into BAT and heart without any rise of
      plasma insulin level. In UCP1-KO mice, the stimulatory effect of NE on 2-DG
      uptake into BAT, but not into heart, disappeared completely. Insulin
      administration increased 2-DG uptake into BAT and also heart similarly in WT and
      UCP1-KO mice. NE also increased the activity of AMP-activated protein kinase (AMP
      kinase) in BAT of WT but not UCP1-KO mice. Our results, together with reports
      that the activation of AMP kinase increases glucose transport in myocytes,
      suggest that the sympathetically stimulated glucose utilization in BAT is due to
      the serial activation of UCP1 and AMP kinase.

PMID- 15855325
TI  - Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose
      tissue in vivo.
AB  - Thiazolidenediones such as pioglitazone improve insulin sensitivity in diabetic
      patients by several mechanisms, including increased uptake and metabolism of free
      fatty acids in adipose tissue. The purpose of the present study was to determine
      the effect of pioglitazone on mitochondrial biogenesis and expression of genes
      involved in fatty acid oxidation in subcutaneous fat. Patients with type 2
      diabetes were randomly divided into two groups and treated with placebo or
      pioglitazone (45 mg/day) for 12 weeks. Mitochondrial DNA copy number and
      expression of genes involved in mitochondrial biogenesis were quantified by real
      time PCR. Pioglitazone treatment significantly increased mitochondrial copy
      number and expression of factors involved in mitochondrial biogenesis, including
      peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1alpha and
      mitochondrial transcription factor A. Treatment with pioglitazone stimulated the
      expression of genes in the fatty acid oxidation pathway, including carnitine
      palmitoyltransferase-1, malonyl-CoA decarboxylase, and medium-chain acyl-CoA
      dehydrogenase. The expression of PPAR-alpha, a transcriptional regulator of genes
      encoding mitochondrial enzymes involved in fatty acid oxidation, was higher after
      pioglitazone treatment. Finally, the increased mitochondrial copy number and the
      higher expression of genes involved in fatty acid oxidation in human adipocytes
      may contribute to the hypolipidemic effects of pioglitazone.

PMID- 15855326
TI  - Donor treatment with carbon monoxide can yield islet allograft survival and
      tolerance.
AB  - Treatment of animals or certain cells with carbon monoxide (CO), a product of
      heme degradation by heme oxygenase-1 (HO-1), has potent anti-inflammatory and
      antiapoptotic effects that contribute to the survival of transplanted organs. We
      report here that inducing HO-1 in, or administering CO to, only the donor can be
      used in a therapeutic manner to sustain the survival of transplanted allogeneic
      islets. Similar treatments of only the islets or only the recipient are also
      salutary. Administering CO only to the donor frequently leads to long-term
      survival of those islets in untreated allogeneic recipients, which are then
      antigen-specifically tolerant. Several proinflammatory and proapoptotic genes
      that are strongly induced in islets after transplantation in the untreated
      situation were significantly suppressed after administering CO to the donor
      without further treatment. These included tumor necrosis factor-alpha, inducible
      nitric oxide synthase, monocyte chemoattractant protein-1, granzyme B, and
      Fas/Fas ligand, all of which contribute to the pathogenesis of the rejection of
      transplanted islets. This correlated with a lesser infiltration of recipient
      macrophages into the transplanted islets. Our present findings show that
      induction of HO-1 in, or administration of CO to, only the donor, islets, or the
      recipient or combinations of such treatments improve allogeneic islet survival.

PMID- 15855327
TI  - Functional defects and the influence of age on the frequency of CD4+ CD25+ T
      cells in type 1 diabetes.
AB  - CD4+ CD25+ T-cells appear to play a crucial role in regulating the immune
      response. Therefore, we evaluated the peripheral blood frequency and function of
      CD4+ CD25+ T-cells in 70 type 1 diabetic patients and 37 healthy individuals.
      Interestingly, a positive correlation was observed between increasing age and
      CD4+ CD25+ T-cell frequency in both subject groups. In contrast to previous
      studies of nonobese diabetic mice and type 1 diabetic patients, similar
      frequencies of CD4+ CD25+ and CD4+ CD25(+Bright) T-cells were observed in healthy
      control subjects and type 1 diabetic patients of similar age. There was no
      difference between type 1 diabetic subjects of recent-onset versus those with
      established disease in terms of their CD4+ CD25+ or CD4+ CD25(+Bright) T-cell
      frequency. However, type 1 diabetic patients were markedly defective in their
      ability to suppress the proliferation of autologous effector T-cells in vitro.
      This type 1 diabetes-associated defect in suppression was associated with reduced
      production of interleukin (IL)-2, gamma-interferon, and transforming growth
      factor-beta, whereas other cytokines including those of adaptive and innate
      immunity (IL-10, IL-1beta, IL-6, IL-8, IL-12p70, and tumor necrosis factor-alpha)
      were similar in control subjects and type 1 diabetic patients. These data suggest
      that age strongly influences the frequency of CD4+ CD25+ T-cells and that
      function, rather than frequency, may represent the means by which these cells
      associate with type 1 diabetes in humans.

PMID- 15855328
TI  - Autoimmune diabetes onset results from qualitative rather than quantitative age
      dependent changes in pathogenic T-cells.
AB  - Diabetogenic T-cells can be detected in pre-diabetic nonobese diabetic (NOD) mice
      after transfer in NOD-SCID recipients. Here we demonstrate that 6-week-old pre
      diabetic NOD mice, >2 months before disease onset, already harbor pathogenic T
      cells in equal numbers to overtly diabetic animals. The delay in diabetes
      appearance is explained by the presence of regulatory CD4+ CD25+ T-cells that
      control diabetogenic effectors and that are, in our hands, transforming growth
      factor (TGF)-beta-dependent. Our present results suggest, however, that diabetes
      onset is only partly explained by a decline in this regulatory T-cell activity.
      Another major factor appears to be the progressive resistance of diabetogenic
      cells to TGF-beta-dependent mediated inhibition. We propose that progression to
      overt disease correlates with the pathogenic T-cell's escape from TGF-beta
      dependent T-cell-mediated regulation.

PMID- 15855329
TI  - Tumor suppressor p53 inhibits autoimmune inflammation and macrophage function.
AB  - The tumor suppressor p53 regulates apoptosis, cell cycle, and oncogenesis. To
      explore the roles of p53 in autoimmunity, we studied type 1 diabetes and innate
      immune responses using C57BL/6 mice deficient in p53. We found that p53-deficient
      mice were more susceptible to streptozotocin-induced diabetes than control mice,
      and they produced higher levels of interleukin-1, -6, and -12. The innate immune
      response of p53-/- macrophages to lipopolysaccharides and gamma-interferon was
      significantly enhanced compared with p53+/+ cells. p53-/- macrophages produced
      more proinflammatory cytokines and higher levels of total and phosphorylated
      signal transducer and activator of transcription (STAT)-1. These results indicate
      that p53 inhibits autoimmune diabetes and innate immune responses through
      downregulating STAT-1 and proinflammatory cytokines.

PMID- 15855330
TI  - Sphingosine kinase activity and sphingosine-1 phosphate production in rat
      pancreatic islets and INS-1 cells: response to cytokines.
AB  - Sphingosine-1 phosphate (S1P) is a bioactive sphingolipid with the potential to
      mobilize Ca2+, to inhibit apoptosis, and to promote mitogenesis. Sphingosine
      kinase (SPHK) and S1P were characterized in INS-1 insulinoma cells and isolated
      rat islets of Langerhans. SPHK activity increased in INS-1 cell homogenates
      treated with interleukin-1beta (IL-1beta) or tumor necrosis factor-alpha (TNF
      alpha), and responses were additive. IL-1beta or TNF-alpha increased islet SPHK
      activity within 15 min to 1 h; activity remained elevated after 8 h. SPHK2 was
      the predominant active isoform in INS-1 cells; little or no SPHK1 activity was
      detected. Cytokines increased endogenous S1P biosynthesis in 32P(i)-prelabeled
      INS-1 cells, and cycloheximide inhibited the response after 8 h, suggesting that
      protein synthesis mediated the response. There was no [32P]S1P release from
      cells. Compared with basal values, IL-1beta and TNF-alpha induced increases in
      SPHK1a mRNA levels relative to 18S ribosomal RNA in INS-1 cells within 1 h;
      relative SPHK2 mRNA levels were unchanged after cytokine treatment. IL-1beta, but
      not TNF-alpha, induced relative SPHK1a mRNA expression levels within 1 h in
      islets, whereas SPHK2 mRNA levels were unchanged. Thus, IL-1beta and TNF-alpha
      induced an early and sustained increase in SPHK activity in INS-1 cells and
      isolated islets, suggesting that S1P plays a role in the pathological response of
      pancreatic beta-cells to cytokines.

PMID- 15855331
TI  - MnSOD and catalase transgenes demonstrate that protection of islets from
      oxidative stress does not alter cytokine toxicity.
AB  - Reactive oxygen species (ROS) and nitric oxide (NO) are proposed mediators of
      cytokine-induced beta-cell destruction in type 1 diabetes. We produced transgenic
      mice with increased beta-cell expression of manganese superoxide dismutase
      (MnSOD) and catalase. Expression of these antioxidants increased beta-cell ROS
      scavenging and improved beta-cell survival after treatment with different sources
      of ROS. MnSOD or catalase conferred protection against streptozotocin (STZ)
      induced beta-cell injury. Coexpression of MnSOD and catalase provided synergistic
      protection against peroxynitrite and STZ. To determine the potential effect of
      these antioxidants on cytokine-induced toxicity, we exposed isolated islets to a
      cytokine mixture, including interleukin-1beta and interferon-gamma. Cytokine
      toxicity was measured as reduced metabolic activity after 6 days and reduced
      insulin secretion after 1 day. Cytokines increased ROS production, and both
      antioxidants were effective in reducing cytokine-induced ROS. However, MnSOD
      and/or catalase provided no protection against cytokine-induced injury. To
      understand this, the nuclear factor-kappaB (NF-kappaB) signaling cascade was
      investigated. Antioxidants reduced NF-kappaB activation by ROS, but none of the
      antioxidants altered activation by cytokines, as measured by inhibitor of kappaB
      phosphorylation, NF-kappaB translocation, inducible NO synthase activation, and
      NO production. Our data agree with previous reports that antioxidants benefit
      beta-cell survival against ROS damage, but they are not consistent with reports
      that antioxidants reduce cytokine toxicity. ROS appear to have no role in
      cytokine toxicity in primary beta-cells.

PMID- 15855332
TI  - Insulin signaling in the central nervous system is critical for the normal
      sympathoadrenal response to hypoglycemia.
AB  - Hypoglycemia, hypoglycemia unawareness, and impaired counterregulation are major
      challenges to the intensive management of type 1 diabetes. While the
      counterregulatory response to hypoglycemia is predominantly determined by the
      degree and duration of hypoglycemia, there is now evidence that insulin per se
      may influence the counterregulatory response to hypoglycemia. To define the role
      of insulin action in the central nervous system in regulating the
      counterregulatory response to hypoglycemia, mice with a brain/neuron-specific
      insulin receptor knockout (NIRKO) and littermate controls were subjected to 90
      min hyperinsulinemic (20 mU x kg(-1) x min(-1)) -hypoglycemic (approximately 1.5
      mmol/l) clamps. In response to hypoglycemia, epinephrine levels rose 5.7-fold in
      controls but only 3.5-fold in NIRKO mice. Similarly, in response to hypoglycemia,
      norepinephrine levels rose threefold in controls, but this response was almost
      completely absent in NIRKO mice. In contrast, glucagon and corticosterone
      responses to hypoglycemia were similar in both groups. Thus, insulin action in
      the brain is critical for full activation of the sympathoadrenal response to
      hypoglycemia, and altered neural insulin signaling could contribute to defective
      glucose counterregulation in diabetes.

PMID- 15855333
TI  - Pyruvate administered after severe hypoglycemia reduces neuronal death and
      cognitive impairment.
AB  - Hypoglycemia-induced brain injury is a significant obstacle to optimal blood
      glucose control in diabetic patients. Severe hypoglycemia triggers a cascade of
      events in vulnerable neurons that may culminate in cell death even after glucose
      normalization. A key event in this cascade is the activation of poly(ADP-ribose)
      polymerase-1 (PARP-1). Activated PARP-1 consumes cytosolic NAD, and because NAD
      is required for glycolysis, hypoglycemia-induced PARP-1 activation may render
      cells unable to use glucose even when glucose availability is restored. Pyruvate,
      however, can be metabolized in the absence of cytosolic NAD. Here we tested
      whether pyruvate could improve the outcome in rats subjected to insulin-induced
      hypoglycemia by terminating hypoglycemia with either glucose alone or glucose
      plus pyruvate. In the four brain regions studied--CA1, subiculum, dentate gyrus
      of the hippocampus, and piriform cortex--the addition of pyruvate reduced neuron
      death by 70-90%. Improved neuron survival was also observed when pyruvate
      delivery was delayed for up to 3 h. The improved neuron survival was accompanied
      by a sustained improvement in cognitive function as assessed by the Morris water
      maze. These results suggest that pyruvate may significantly improve the outcome
      after severe hypoglycemia by circumventing a sustained impairment in neuronal
      glucose utilization resulting from PARP-1 activation.

PMID- 15855334
TI  - Effects of metformin and rosiglitazone treatment on insulin signaling and glucose
      uptake in patients with newly diagnosed type 2 diabetes: a randomized controlled
      study.
AB  - The effect of metformin or rosiglitazone monotherapy versus placebo on insulin
      signaling and gene expression in skeletal muscle of patients with newly diagnosed
      type 2 diabetes was determined. A euglycemic-hyperinsulinemic clamp, combined
      with skeletal muscle biopsies and glucose uptake measurements over rested and
      exercised muscle, was performed before and after 26 weeks of metformin (n = 9),
      rosiglitazone (n = 10), or placebo (n = 11) treatment. Insulin-mediated whole
      body and leg muscle glucose uptake was enhanced 36 and 32%, respectively, after
      rosiglitazone (P < 0.01) but not after metformin or placebo treatment. Insulin
      increased insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation, IRS-1
      associated phosphatidylinositol (PI) 3-kinase activity, and phosphorylation of
      Akt Ser473 and AS160, a newly described Akt substrate that plays a role in GLUT4
      exocytosis, approximately 2.3 fold before treatment. These insulin signaling
      parameters were unaltered after metformin, rosiglitazone, or placebo treatment.
      Expression of selected genes involved in glucose and fatty acid metabolism in
      skeletal muscle was unchanged between the treatment groups. Low-intensity acute
      exercise increased insulin-mediated glucose uptake but was without effect on
      insulin signaling. In conclusion, the insulin-sensitizing effects of
      rosiglitazone are independent of enhanced signaling of IRS-1/PI 3
      kinase/Akt/AS160 in patients with newly diagnosed type 2 diabetes.

PMID- 15855335
TI  - Demonstration of a hyperglycemia-driven pathogenic abnormality of copper
      homeostasis in diabetes and its reversibility by selective chelation:
      quantitative comparisons between the biology of copper and eight other
      nutritionally essential elements in normal and diabetic individuals.
AB  - We recently showed that treatment with the Cu(II)-selective chelator, trientine,
      alleviates heart failure in diabetic rats, improves left ventricular hypertrophy
      in humans with type 2 diabetes, and increases urinary Cu excretion in both
      diabetic rats and humans compared with nondiabetic control subjects. In this
      study, we characterized the homeostasis of Cu and eight other nutritionally
      essential elements in diabetes under fully residential conditions in male
      subjects with type 2 diabetes and age-matched control subjects. We then probed
      elemental balance with oral trientine in a parallel-group, placebo-controlled
      study in these subjects. Before treatment, there were no detectable between-group
      differences in the balance of any element, although urinary output of several
      elements was greater in diabetic subjects. Mean extracellular superoxide
      dismutase (EC-SOD) activity was elevated in diabetic subjects, and its activity
      correlated strongly with the interaction between [Cu]serum and HbA1c. Trientine
      caused the Cu balance to become negative in diabetic subjects through elevated
      urinary Cu losses and suppressed elevated EC-SOD. Basal urinary Cu predicted
      urinary Cu losses during treatment, which caused extraction of systemic Cu(II).
      We suggest that cardiovascular complications in diabetes might be better
      controlled by therapeutic strategies that focus on lowering plasma glucose and
      loosely bound systemic Cu(II).

PMID- 15855336
TI  - G(-) anaerobes-reactive CD4+ T-cells trigger RANKL-mediated enhanced alveolar
      bone loss in diabetic NOD mice.
AB  - Diabetic patients experience a higher risk for severe periodontitis; however, the
      underlying mechanism remains unclear. We investigated the contribution of
      antibacterial T-cell-mediated immunity to enhanced alveolar bone loss during
      periodontal infection in nonobese diabetic (NOD) mice by oral inoculation with
      Actinobacillus actinomycetemcomitans, a G(-) anaerobe responsible for juvenile
      and severe periodontitis. The results show that 1) inoculation with A.
      actinomycetemcomitans in pre-diabetic NOD mice does not alter the onset,
      incidence, and severity of diabetes; 2) after A. actinomycetemcomitans
      inoculation, diabetic NOD mice (blood glucose >200 mg/dl and with severe
      insulitis) exhibit significantly higher alveolar bone loss compared with pre
      diabetic and nondiabetic NOD mice; and 3) A. actinomycetemcomitans-reactive CD4+
      T-cells in diabetic mice exhibit significantly higher proliferation and receptor
      activator of nuclear factor kappaB ligand (RANKL) expression. When diabetic mice
      are treated with the RANKL antagonist osteoprotegerin (OPG), there is a
      significant reversal of alveolar bone loss, as well as reduced RANKL expression
      in A. actinomycetemcomitans-reactive CD4+ T-cells. This study clearly describes
      the impact of autoimmunity to anaerobic infection in an experimental
      periodontitis model of type 1 diabetes. Thus, microorganism-reactive CD4+ T-cells
      and the RANKL-OPG axis provide the molecular basis of the advanced periodontal
      breakdown in diabetes and, therefore, OPG may hold therapeutic potential for
      treating bone loss in diabetic subjects at high risk.

PMID- 15855337
TI  - Nonproteinuric diabetes-associated nephropathy in the Cohen rat model of type 2
      diabetes.
AB  - The Cohen diabetic rat is an experimental model reminiscent of human type 2
      diabetes. The aim of this study was to characterize the development of end-organ
      damage in this model. Cohen diabetic sensitive (CDs) and Cohen diabetic resistant
      (CDr) rats were fed regular diet or a diabetogenic diet. Glucose tolerance, renal
      function, and renal and retinal histology were studied at set intervals. CDs fed
      diabetogenic diet were the only strain that expressed the diabetic metabolic
      phenotype. In this strain, urinary protein excretion did not increase with the
      development of diabetes, but plasma urea and creatinine levels increased and
      creatinine clearance decreased. Light microscopy revealed in CDs enlarged
      glomeruli with increased mesangial matrix and thickening of the glomerular
      capillary wall; electron microscopy demonstrated thickened basement membrane and
      mesangial abundance. There was increased staining for type IV collagen in
      glomeruli and interstitium of CDs. The retinas of diabetic CDs demonstrated
      pathology consistent with nonproliferative diabetic retinopathy. The histological
      findings in the kidneys, the absence of proteinuria, the impairment in glomerular
      filtration, and the development of retinopathy in CDs are consistent with
      diabetes-associated nephropathy that is similar to a nonalbuminuric type of
      nephropathy associated with type 2 diabetes in humans.

PMID- 15855338
TI  - The effect of C-peptide on cognitive dysfunction and hippocampal apoptosis in
      type 1 diabetic rats.
AB  - Primary diabetic encephalopathy is a recently recognized late complication of
      diabetes resulting in a progressive decline in cognitive faculties. In the
      spontaneously type 1 diabetic BB/Wor rat, we recently demonstrated that cognitive
      impairment was associated with hippocampal apoptotic neuronal loss. Here, we
      demonstrate that replacement of proinsulin C-peptide in this insulinopenic model
      significantly prevented spatial learning and memory deficits and hippocampal
      neuronal loss. C-peptide replacement prevented oxidative stress-, endoplasmic
      reticulum-, nerve growth factor receptor p75-, and poly(ADP-ribose) polymerase
      related apoptotic activities. It partially ameliorated apoptotic stresses
      mediated via impaired insulin and IGF activities. These findings were associated
      with the prevention of increased expression of Bax and active caspase 3 and the
      frequency of caspase 3-positive neurons. The results show that several partially
      interrelated apoptotic mechanisms are involved in primary encephalopathy and
      suggest that impaired insulinomimetic action by C-peptide plays a prominent role
      in cognitive dysfunction and hippocampal apoptosis in type 1 diabetes. Although
      these abnormalities were not fully prevented by C-peptide replacement, the
      findings suggest that this regime will substantially prevent cognitive decline in
      the type 1 diabetic population.

PMID- 15855339
TI  - Linoleic acid increases lectin-like oxidized LDL receptor-1 (LOX-1) expression in
      human aortic endothelial cells.
AB  - Results from in vitro studies suggest that selected fatty acids, and especially
      linoleic acid (LA), can elicit endothelial dysfunction (ED). Because LA is
      increased in all LDL subfractions in patients with type 2 diabetes, this
      alteration may contribute to ED associated with diabetes. Lectin-like oxidized
      LDL receptor-1 (LOX-1) is the major endothelial receptor for oxidized LDL
      (oxLDL), and uptake of oxLDL through LOX-1 induces ED. To evaluate whether LA may
      contribute to the upregulation of endothelial LOX-1 in diabetes, we studied the
      effect of LA on LOX-1 expression in cultured human aortic endothelial cells
      (HAECs). Treatment of HAECs with LA increased, in a time- and dose-dependent
      manner, endothelial LOX-1 protein expression. Pretreatment of HAECs with
      antioxidants and inhibitors of NADPH oxidase, protein kinase C (PKC), and nuclear
      factor-kappaB (NF-kappaB) inhibited the stimulatory effect of LA on LOX-1 protein
      expression. Furthermore, in LA-treated HAECs, increased expression of classic PKC
      isoforms was observed. LA also led to a significant increase in LOX-1 gene
      expression and enhanced the binding of nuclear proteins extracted from HAECs to
      the NF-kappaB regulatory element of the LOX-1 gene promoter. Finally, LA
      enhanced, through LOX-1, oxLDL uptake by endothelial cells. Overall, these
      results demonstrate that LA enhances endothelial LOX-1 expression through
      oxidative stress-sensitive and PKC-dependent pathways. This effect seems to be
      exerted at the transcriptional level and to involve the activation of NF-kappaB.
      Upregulation of LOX-1 by LA may contribute to ED associated with type 2 diabetes.

PMID- 15855340
TI  - Low-dose poly(ADP-ribose) polymerase inhibitor-containing combination therapies
      reverse early peripheral diabetic neuropathy.
AB  - Poly(ADP-ribose) polymerase (PARP) inhibition has recently been identified as a
      novel approach to treatment of experimental peripheral diabetic neuropathy (PDN).
      However, long-term inhibition of PARP, an enzyme involved in DNA repair, can
      potentially result in premature aging, loss of genome stability, and other side
      effects. This study evaluated potential synergistic interactions between low
      doses of the potent and specific PARP inhibitor 1,5-isoquinolinediol (ISO) and
      one of two vasodilators, the ACE inhibitor lisinopril (LIS) and the beta2
      adrenoceptor agonist salbutamol (SAL) in the model of early PDN. Control and
      streptozotocin (STZ)-induced diabetic rats were treated with either ISO plus LIS
      or ISO plus SAL for 2 weeks after an initial 2 weeks without treatment. ISO
      (intraperitoneally) and LIS and SAL (both in the drinking water) were used in
      subtherapeutic doses, resulting in a minor correction of diabetes-associated
      sciatic motor and hind-limb digital sensory nerve conduction deficits when
      administered as monotherapies. Both combination treatments corrected endoneurial
      blood flow and vascular conductance deficits in STZ-induced diabetic rats. ISO
      plus SAL corrected all other changes of PDN, i.e., motor nerve conduction
      velocity (MNCV) and sensory nerve conduction velocity (SNCV) deficits as well as
      thermal and mechanical hyperalgesia. With ISO plus LIS, no significant correction
      of MNCV was observed, and the effect on thermal hyperalgesia was quite modest.
      SNCV and mechanical hyperalgesia were corrected. In vitro studies in human
      endothelial and Schwann cells showed early accumulation of poly(ADP-ribosyl)ated
      proteins (Western blot analysis) in response to high glucose, thus suggesting the
      importance of PARP activation in human PDN. In conclusion, low-dose PARP
      inhibitor-containing combination therapies may constitute a new approach for
      treatment of PDN.

PMID- 15855341
TI  - Mannose-binding lectin as a predictor of microalbuminuria in type 1 diabetes: an
      inception cohort study.
AB  - Inflammation and complement activation via the mannose-binding lectin (MBL)
      pathway have been suggested to play a role in the pathogenesis of diabetic
      microvascular complications. The association between the complement-activating
      protein MBL and the development of persistent microalbuminuria was evaluated in
      an inception cohort of 286 newly diagnosed type 1 diabetic patients consecutively
      admitted to the Steno Diabetes Center between 1 September 1979 and 31 August
      1984. Serum MBL was measured with an immunofluorometric assay in 270 of the
      patients (159 men) after 3 years of diabetes duration. During the median (range)
      follow-up period of 18.0 (1.0-21.8) years, 75 patients subsequently progressed to
      persistent micro- or macroalbuminuria (urinary albumin excretion rate >30 mg/24
      h). In patients with MBL levels above the median (1,597 microg/l), the cumulative
      incidence of persistent micro- or macroalbuminuria was 41% (CI 31-50) as compared
      with 26% (CI 17-34) in patients with MBL levels below the median (log-rank test,
      P = 0.003). In a Cox proportional hazard model with sex and age as fixed
      covariates, MBL was independently associated with later development of persistent
      micro- or macroalbuminuria (hazard ratio 1.21 [CI 1.02-1.42] per 1,000 microg/l
      increase in MBL; P = 0.03) after adjusting for possible confounders. In our
      study, high levels of MBL early in the course of type 1 diabetes was
      significantly associated with later development of persistent micro- or
      macroalbuminuria, suggesting that complement activation initiated by MBL may be
      involved in the pathogenesis of diabetic microvascular complications.

PMID- 15855342
TI  - Reduced insulin and IGF-I signaling, not hyperglycemia, underlies the diabetes
      associated depletion of interstitial cells of Cajal in the murine stomach.
AB  - Damage to interstitial cells of Cajal (ICC), pacemakers, and mediators of
      neuromuscular neurotransmission in the gastrointestinal tract contributes to the
      pathogenesis of diabetic gastroenteropathy in both patients and animal models.
      ICC depletion in diabetes may result from chronic hyperglycemia or
      lost/ineffective insulin signaling. Because independent control of insulin and
      glucose concentrations is difficult in chronic in vivo studies, we used long-term
      organotypic cultures to address this problem. Murine gastric muscles were
      cultured in normoglycemic or hyperglycemic basal media with or without insulin or
      IGF-I for 1-3 months, the time required for gastroparesis and ICC damage to
      develop in diabetic mice. ICC were assessed by c-Kit immunohistochemistry and
      quantitative analysis of c-kit expression. Electrical pacemaking was studied by
      intracellular recording of slow waves. ICC survived for at least 34 days in
      unsupplemented normoglycemic media, but their networks, c-kit expression, and
      slow waves were profoundly reduced after 68 days. These changes could be entirely
      prevented by insulin or IGF-I supplementation. ICC networks were completely
      resistant to hyperglycemia for at least 72 days. Thus, hyperglycemia is unlikely
      to be responsible for the diabetes-associated depletion of ICC. In contrast,
      maintenance of ICC requires insulin or IGF-I, which are reduced or ineffective in
      diabetes.

PMID- 15855343
TI  - Neutrophils are associated with capillary closure in spontaneously diabetic
      monkey retinas.
AB  - Type 2 diabetes develops spontaneously in obese aging rhesus monkeys (Macaca
      mulatta). This study investigates the association between polymorphonuclear
      leukocytes and development of retinopathy. Blood pressure and plasma glucose
      levels were determined in 15 diabetic and 6 nondiabetic monkeys. The plasma
      levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides
      were determined just before the start of the animal's final decline and elective
      necropsy. Retinas were incubated for ADPase (labels viable retinal blood vessels)
      and nonspecific esterase (labels neutrophils) activities. Polymorphonuclear
      leukocytes were counted per millimeter squared of retina. After the retina was
      flat-embedded in glycol methacrylate, tissue sections were taken through areas of
      interest and observed microscopically. Elevated numbers of intravascular
      polymorphonuclear leukocytes were present adjacent to areas with retinal
      capillary nonperfusion. There were significantly more polymorphonuclear
      leukocytes per millimeter squared in diabetic retinas (6.91 +/- 5.01) compared
      with normal retinas (1.45 +/- 1.62, P = 0.018). Severity of hypertension in
      diabetes was also significantly associated with greater numbers of
      polymorphonuclear leukocytes (P = 0.02). There was a significant positive
      exponential correlation between the number of polymorphonuclear leukocytes per
      millimeter squared and the level of total cholesterol (R = 0.907), LDL
      cholesterol (R = 0.875), the total cholesterol-to-HDL cholesterol ratio (R =
      0.86), and total triglycerides (R = 0.888). This study demonstrates that severity
      of diabetes and the development of retinopathy are associated with increased
      numbers of polymorphonuclear leukocytes in the retina of diabetic monkeys.
      Hypertension, high plasma levels of LDL cholesterol and triglycerides, and low
      plasma levels of HDL cholesterol also are associated with increased
      polymorphonuclear leukocytes in retina.

PMID- 15855344
TI  - Wound inflammation in diabetic ob/ob mice: functional coupling of prostaglandin
      biosynthesis to cyclooxygenase-1 activity in diabetes-impaired wound healing.
AB  - This study focused on the regulation of prostaglandin (PG) production in diabetes
      impaired wound tissue. Cyclooxygenase (COX)-1 and -2 expression and activity were
      severely dysregulated in chronic wounds of diabetic ob/ob mice. Those wounds were
      characterized by a reduced expression of COX-1 and the presence of strongly
      elevated levels of COX-2 when compared with conditions observed in healthy
      animals. Resolution of the diabetic and impaired wound-healing phenotype by
      systemic administration of leptin into ob/ob mice increased COX-1 expression in
      wound margin keratinocytes and decreased COX-2 expression in inner wound areas to
      levels found in wild-type animals. Notably, improved wound healing was
      characterized by a marked increase in PGE2/PGD2 biosynthesis that colocalized
      with induced COX-1 in new tissue at the margin of the wound. COX-2 expression did
      not significantly contribute to PGE2/PGD2 production in impaired wound tissue.
      Accordingly, only late wound tissue from SC-560-treated (selective COX-1
      inhibitor) but not celecoxib-treated (selective COX-2 inhibitor) ob/ob mice
      exhibited a severe loss in PGE2, PGD2, and prostacyclin at the wound site, and
      this change was associated with reduced keratinocyte numbers in the neo
      epithelia. These data constitute strong evidence that a dysregulation of COX-1
      coupled prostaglandin contributes to diabetes-impaired wound healing.

PMID- 15855345
TI  - Inhibitory effects of antipsychotics on carbachol-enhanced insulin secretion from
      perifused rat islets: role of muscarinic antagonism in antipsychotic-induced
      diabetes and hyperglycemia.
AB  - Treatment with the atypical antipsychotics olanzapine and clozapine has been
      associated with an increased risk for deterioration of glucose homeostasis,
      leading to hyperglycemia, ketoacidosis, and diabetes, in some cases independent
      of weight gain. Because these events may be a consequence of their ability to
      directly alter insulin secretion from pancreatic beta-cells, we determined the
      effects of several antipsychotics on cholinergic- and glucose-stimulated insulin
      secretion from isolated rat islets. At concentrations encompassing
      therapeutically relevant levels, olanzapine and clozapine reduced insulin
      secretion stimulated by 10 micromol/l carbachol plus 7 mmol/l glucose. This
      inhibition of insulin secretion was paralleled by significant reductions in
      carbachol-potentiated inositol phosphate accumulation. In contrast, risperidone
      or ziprasidone had no adverse effect on cholinergic-induced insulin secretion or
      inositol phosphate accumulation. None of the compounds tested impaired the islet
      secretory responses to 8 mmol/l glucose alone. Finally, in vitro binding and
      functional data show that olanzapine and clozapine (unlike risperidone,
      ziprasidone, and haloperidol) are potent muscarinic M3 antagonists. These
      findings demonstrate that low concentrations of olanzapine and clozapine can
      markedly and selectively impair cholinergic-stimulated insulin secretion by
      blocking muscarinic M3 receptors, which could be one of the contributing factors
      to their higher risk for producing hyperglycemia and diabetes in humans.

PMID- 15855346
TI  - Minocycline reduces proinflammatory cytokine expression, microglial activation,
      and caspase-3 activation in a rodent model of diabetic retinopathy.
AB  - Diabetes leads to vascular leakage, glial dysfunction, and neuronal apoptosis
      within the retina. The goal of the studies reported here was to determine the
      role that retinal microglial cells play in diabetic retinopathy and assess
      whether minocycline can decrease microglial activation and alleviate retinal
      complications. Immunohistochemical analyses showed that retinal microglia are
      activated early in diabetes. Furthermore, mRNAs for interleukin-1beta and tumor
      necrosis factor-alpha, proinflammatory mediators known to be released from
      microglia, are also increased in the retina early in the course of diabetes.
      Using an in vitro bioassay, we demonstrated that cytokine-activated microglia
      release cytotoxins that kill retinal neurons. Furthermore, we showed that
      neuronal apoptosis is increased in the diabetic retina, as measured by caspase-3
      activity. Minocycline represses diabetes-induced inflammatory cytokine
      production, reduces the release of cytotoxins from activated microglia, and
      significantly reduces measurable caspase-3 activity within the retina. These
      results indicate that inhibiting microglial activity may be an important strategy
      in the treatment of diabetic retinopathy and that drugs such as minocycline hold
      promise in delaying or preventing the loss of vision associated with this
      disease.

PMID- 15855347
TI  - Intensive lifestyle intervention or metformin on inflammation and coagulation in
      participants with impaired glucose tolerance.
AB  - Increases in subclinical inflammation (C-reactive protein [CRP]) and impaired
      coagulation have been associated with increased obesity and insulin resistance.
      Only a few small studies have examined the effect of lifestyle changes, such as
      weight loss, increased physical activity, and insulin-sensitizing intervention on
      inflammation and coagulation. The Diabetes Prevention Program (DPP) clinical
      trial studied the effect of an intensive lifestyle intervention or metformin on
      progression to diabetes relative to placebo in 3,234 adults with impaired glucose
      tolerance. The effects of these interventions on CRP and fibrinogen at 12 months
      are examined in this report. Metformin reduced CRP in women compared with the
      placebo group. In men, the median changes in CRP from baseline to 1 year were 
      33% in the lifestyle group, -7% in the metformin group, and +5% in the placebo
      group. In women, the changes in CRP from baseline to follow-up were -29% in the
      lifestyle group, -14% in the metformin group, and 0% in the placebo group. In the
      lifestyle group weight loss rather than increased physical activity seems to
      account for most of the changes in CRP. Only modest reductions (although
      significant) were seen in fibrinogen levels in the lifestyle group relative to
      the metformin and placebo group. Lifestyle intervention reduced levels of
      nontraditional cardiovascular risk factors relative to both placebo and to a
      lesser degree to metformin.

PMID- 15855348
TI  - Kallikrein gene delivery improves serum glucose and lipid profiles and cardiac
      function in streptozotocin-induced diabetic rats.
AB  - We investigated the role of the kallikrein-kinin system in cardiac function and
      glucose utilization in the streptozotocin (STZ)-induced diabetic rat model using
      a gene transfer approach. Adenovirus harboring the human tissue kallikrein gene
      was administered to rats by intravenous injection at 1 week after STZ treatment.
      Human kallikrein transgene expression was detected in the serum and urine of STZ
      induced diabetic rats after gene transfer. Kallikrein gene delivery significantly
      reduced blood glucose levels and cardiac glycogen accumulation in STZ-induced
      diabetic rats. Kallikrein gene transfer also significantly attenuated elevated
      plasma triglyceride and cholesterol levels, food and water intake, and loss of
      body weight gain, epididymal fat pad, and gastrocnemius muscle weight in STZ
      induced diabetic rats. However, these effects were blocked by icatibant, a kinin
      B2 receptor antagonist. Cardiac function was significantly improved after
      kallikrein gene transfer as evidenced by increased cardiac output and +/-delta
      P/delta t (maximum speed of contraction/relaxation), along with elevated cardiac
      sarco(endo)plasmic reticulum (Ca2+ + Mg2+)-ATPase (SERCA)-2a, phosphorylated
      phospholamban, NOx and cAMP levels, and GLUT4 translocation into plasma membranes
      of cardiac and skeletal muscle. Kallikrein gene delivery also increased Akt and
      glycogen synthase kinase (GSK)-3beta phosphorylation, resulting in decreased GSK
      3beta activity in the heart. These results indicate that kallikrein through kinin
      formation protects against diabetic cardiomyopathy by improving cardiac function
      and promoting glucose utilization and lipid metabolism.

PMID- 15855349
TI  - Subcellular localization of ALMS1 supports involvement of centrosome and basal
      body dysfunction in the pathogenesis of obesity, insulin resistance, and type 2
      diabetes.
AB  - Alstrom syndrome is a rare autosomal recessive disorder caused by mutations in a
      novel gene of unknown function, ALMS1. Central features of Alstrom syndrome
      include obesity, insulin resistance, and type 2 diabetes, and therefore
      investigating ALMS1 function stands to offer new insights into the pathogenesis
      of these common conditions. To begin this process, we have analyzed the
      subcellular localization and tissue distribution of ALMS1 by immunofluorescence.
      We show that ALMS1 is widely expressed and localizes to centrosomes and to the
      base of cilia. Fibroblasts with disrupted ALMS1 assemble primary cilia and
      microtubule cytoskeletons that appear normal, suggesting that the Alstrom
      syndrome phenotype results from impaired function rather than abnormal
      development. Coupled with recent data on the complex phenotype of Bardet-Biedl
      syndrome, our findings imply an unexpected central role for basal body and
      centrosome dysfunction in the pathogenesis of obesity, insulin resistance, and
      type 2 diabetes. Unraveling the molecular mechanisms underlying the Alstrom
      syndrome phenotype will be important in the search for new therapeutic targets
      for these conditions.

PMID- 15855350
TI  - OAS1 splice site polymorphism controlling antiviral enzyme activity influences
      susceptibility to type 1 diabetes.
AB  - Both genetic and nongenetic factors contribute to the development of type 1
      diabetes. Many investigations, including prospective studies of high-risk
      children, have implicated virus infections as predisposing environmental agents.
      We previously reported that basal activity of the key antiviral enzyme 2'5'
      oligoadenylate synthetase (2'5'AS) was significantly elevated in type 1 diabetic
      patients compared with healthy control subjects. Recently, we showed that an A/G
      splice site single nucleotide polymorphism (SNP) in the OAS1 gene encoding 2'5'AS
      is strongly associated with basal 2'5'AS activity. Basal enzyme activity was
      highest in individuals with GG genotype and lowest in those with AA genotype. In
      the present study, we genotyped 835 type 1 diabetic and 401 healthy siblings at
      the OAS1 splice site polymorphism and (for comparison) at an A/C SNP of the
      insulin (IDDM2) locus. Results showed that OAS1 GG and GA were significantly
      increased in diabetic compared with healthy siblings (P = 0.0023). The strength
      of association was similar to that at IDDM2, where, as expected, the C/C
      (variable number tandem repeat class I homozygote) genotype was increased in
      affected compared with healthy siblings (P = 0.0025). The results suggest that
      host genetic response to virus infection could influence susceptibility to type 1
      diabetes.

PMID- 15855351
TI  - Single nucleotide polymorphisms in K(ATP) channels: muscular impact on type 2
      diabetes.
AB  - ATP-sensitive K+ channels (K(ATP) channels) play an important role in glucose
      homeostasis. A single nucleotide polymorphism (SNP) in the Kir6.2 subunit causes
      a point mutation of Glu23 to lysine and reduces the ATP sensitivity of pancreatic
      K(ATP) channels. The SNP found in 58% of Caucasians accounts for 15% of type 2
      diabetes. Here we show evidence for dysregulations of muscular K(ATP) channels
      with the E23K variation. We were particularly interested in the channel
      modulation by intracellular protons, as pH changes widely and frequently in
      skeletal muscles. Surprisingly, we found that the defect of the E23K variant was
      more related to pH than ATP. A level of intracellular acidification seen during
      exercise not only activated the E23K channel more readily than the wild type, but
      also relieved the channel inhibition by ATP, leading to a vast increase in the
      channel open-state probability by approximately sevenfold at pH 6.8 over the wild
      type channel at pH 7.4. Considering the reduction in sarcolemmal excitability,
      muscle fatigue, and impairment of muscular glucose uptake found previously by
      genetically disrupting K(ATP) channels, it is likely that the E23K variant in
      muscular K(ATP) channels affects systemic glucose homeostasis and poses an
      important risk factor for type 2 diabetes and obesity.

PMID- 15855352
TI  - Variations in peptide YY and Y2 receptor genes are associated with severe obesity
      in Pima Indian men.
AB  - Peptide YY (PYY) and Y2 receptor (Y2R) may be important in the central regulation
      of body weight and food intake. To determine whether genetic variation in PYY
      and/or Y2R may contribute to morbid obesity in humans, these genes were sequenced
      in 83 extremely obese Pima Indians (BMI > or = 50 kg/m2). Sequencing of PYY
      identified three single nucleotide polymorphisms (SNPs) in the untranslated
      region. Sequencing of the Y2R coding region identified one missense (Ala172Thr)
      substitution and two silent substitutions. Eight additional SNPs in the 5'
      untranslated region of Y2R were identified from public databases. These SNPs were
      genotyped in 489 full-heritage adult Pimas (362 severely obese and 127
      nondiabetic, nonobese subjects), who are not first-degree relatives, for
      association analysis. The PYY variants were not associated with obesity, whereas
      four variants from two haplotype blocks in Y2R were marginally associated (P =
      0.054-0.067) with obesity. However, if the analysis was restricted to men (n =
      167, 100 obese and 67 lean), the PYY variants and two SNPs in Y2R that were in
      complete linkage disequilibrium were significantly associated with severe obesity
      (P = 0.001 and P = 0.002, respectively). Our data suggest that the PYY-Y2R
      pathway may influence body weight through a sex-specific mechanism, but this
      finding requires confirmation in other populations.

PMID- 15855353
TI  - Major histocompatibility complex-linked diabetes susceptibility in NOD/Lt mice:
      subcongenic analysis localizes a component of Idd16 at the H2-D end of the
      diabetogenic H2(g7) complex.
AB  - The diabetogenic major histocompatibility complex (MHC) (H2(g7)) of NOD mice
      comprises contributions from several class II loci collectively designated as
      Idd1. Introduction of the H2(gx) haplotype from the related but diabetes
      resistant cataract Shionogi (CTS) strain demonstrated an additional MHC-linked
      locus designated Idd16. The NOD-related alloxan resistant (ALR)/Lt strain is also
      characterized by the H2(gx) haplotype, which does not differ from H2(g7) from the
      class I H2-K(d) gene distally through the class II and into the class III region.
      Polymorphisms distal to the heat shock protein 70 locus (Hspa1b) include a rare
      H2-D(dx) rather than the H2(g7) encoded D(b) allele. Two differential-length
      NOD.ALR-H2(gx) congenic stocks (D.R1 and D.R2), both containing H2-D(dx),
      significantly suppressed diabetogenesis. This protection was lost when ALR
      alleles between the class III region and H2-D were removed in a shorter interval
      congenic (D.R3). Because no differences were observed in the ALR-derived interval
      extending 0.41 mB proximal to H2-K in any of these congenic stocks, a component
      of what was originally designated "Idd16" was sited to an interval shorter than
      7.33 mB, distinguishing D.R2 from D.R3. Evidence supporting the candidacy of the
      ALR/CTS-shared H2-D(dx) MHC class I variant present in both diabetes-resistant
      stocks, but not the susceptible stock, is discussed.

PMID- 15855354
TI  - The +276 polymorphism of the APM1 gene, plasma adiponectin concentration, and
      cardiovascular risk in diabetic men.
AB  - Recently, the genetic variability at adiponectin locus (APM1) was associated with
      cardiovascular risk in patients with type 2 diabetes. We sought to examine the
      associations of five variants of APM1 gene (C-11365G, A-4034C, A-3964G, T45G, and
      G276T) with the risk of cardiovascular diseases (CVDs) in a larger cohort of
      diabetic patients. Of 879 diabetic men from the Health Professionals Follow-up
      Study, 239 participants developed coronary heart disease or stroke during 14
      years of follow-up and 640 CVD-negative subjects were used as control subjects.
      The risk of CVD was significantly lower in TT homozygotes at locus +276 than in
      other genotypes under a recessive inheritance model after adjusting for age, BMI,
      smoking, alcohol consumption, physical activity, aspirin use, HbA1c, and history
      of hypertension or hypercholesterolemia (odds ratio 0.38 [95% CI 0.18-0.79]; P =
      0.009). In the CVD-negative control subjects, the allele 276T was associated with
      significantly higher plasma adiponectin levels in a dose-dependent pattern (GG
      14.8, GT 16.2, and TT 18.8 microg/ml) after adjusting for age, BMI, and other
      variables (P for trend = 0.0019). In conclusion, our study showed significant
      associations between APM1 G276T and decreased CVD risk and increased plasma
      adiponectin levels in diabetic men.

PMID- 15855355
TI  - Pharmacodynamic characterization of ZP120 (Ac-RYYRWKKKKKKK-NH2), a novel,
      functionally selective nociceptin/orphanin FQ peptide receptor partial agonist
      with sodium-potassium-sparing aquaretic activity.
AB  - In conscious rats, intravenous (i.v.) administration of the hexapeptide Ac-RYYRWK
      NH(2), a partial agonist of the nociceptin/orphanin FQ (N/OFQ) peptide (NOP)
      receptor, produces a selective water diuresis without marked cardiovascular or
      behavioral effects. The present study examined the in vitro and in vivo
      pharmacodynamic profile of the novel and potentially metabolically stable NOP
      receptor ligand ZP120 (Ac-RYYRWKKKKKKK-NH(2)), which was created by conjugation
      of a structure-inducing probe (SIP) (i.e., K(6) sequence) to Ac-RYYRWK-NH(2). In
      cells transfected with human NOP receptors, both Ac-RYYRWK-NH(2) and ZP120
      displaced [(3)H]N/OFQ (both peptides, pK(i) = 9.6), and similar to N/OFQ
      inhibited forskolin-induced cAMP formation (Ac-RYYRWK-NH(2), pEC(50) = 9.2;
      ZP120, 9.3; N/OFQ, 9.7). In the mouse vas deferens assay (MVD), Ac-RYYRWK-NH(2)
      and ZP120 behaved as partial agonists, inhibiting electrically induced
      contractions with similar pEC(50) values (9.0 and 8.6, respectively) but with
      submaximal efficacy compared with N/OFQ. In MVD, both peptides blocked the
      responses to N/OFQ, with ZP120 being approximately 50-fold more potent than Ac
      RYYRWK-NH(2). In vivo, dose-response studies in rats showed that at doses (i.v.
      bolus or i.v. infusion) that produced a sodium-potassium-sparing aquaresis, ZP120
      and Ac-RYYRWK-NH(2) elicited a mild vasodilatory response without reflex
      tachycardia. However, the renal responses to ZP120 were of greater magnitude and
      duration. Finally, each peptide blocked the bradycardia and hypotension to N/OFQ
      in conscious rats, but the effect of ZP120 was of much greater duration.
      Together, these findings demonstrate that ZP120 is a novel, functionally
      selective SIP-modified NOP receptor partial agonist with increased biological
      activity and sodium-potassium-sparing aquaretic activity, the actions of which
      may be useful in the management of hyponatremia/hypokalemia in water-retaining
      states.

PMID- 15855356
TI  - Functional selectivity of nociceptin/orphanin FQ peptide receptor partial
      agonists on cardiovascular and renal function.
AB  - The opioid-like peptide nociceptin/orphanin FQ (N/OFQ) produces marked
      cardiovascular and renal responses after central or peripheral administration in
      rats. Due to their ability to behave as full/partial agonists or antagonists in
      different cellular and tissue assays, the present studies were performed to
      determine how compounds classified as N/OFQ peptide (NOP) receptor partial
      agonists ([F/G]N/OFQ(1-13)-NH(2), Ac-RYYRIK-NH(2), and Ac-RYYRWK-NH(2)) affect
      cardiovascular and renal function in vivo. In conscious Sprague-Dawley rats,
      intracerebroventricular (i.c.v.) administration of each of the three NOP receptor
      ligands produced profound cardiovascular (depressor), renal excretory (water
      diuresis), and renal sympathetic nerve activity (inhibitory) responses that were
      similar to those produced by i.c.v. injection of the native ligand N/OFQ. In
      contrast, in other groups of rats, the intravenous (i.v.) bolus injection of
      these same NOP receptor ligands produced responses unlike N/OFQ; N/OFQ evoked an
      immediate and profound bradycardia and hypotension with no change in urine
      output, whereas all purported NOP receptor partial agonists elicited a subtle
      slow onset hypotension, no change in heart rate, and a marked water diuresis. In
      other studies, i.v. bolus pretreatment of rats with NOP receptor partial agonists
      prevented/attenuated the cardiovascular depressor effects produced by a
      subsequent i.v. bolus N/OFQ challenge without affecting the cardiovascular
      responses to i.c.v. N/OFQ. Together, these findings demonstrate that in conscious
      rats, NOP receptor partial agonists produce functionally selective effects on
      cardiovascular and renal function ranging from full agonist (i.c.v.,
      cardiovascular depressor; i.c.v. and i.v., water diuresis), partial agonist
      (i.v., submaximal hypotension) to antagonist (i.v., blockade of N/OFQ-evoked
      bradycardia and hypotension) behavior.

PMID- 15855357
TI  - Fixation of the graft in reconstruction of the anterior cruciate ligament.

PMID- 15855358
TI  - Walking for the severely disabled: research and development, experience and
      clinical outcomes.

PMID- 15855359
TI  - Controversies in the surgical management of skeletal metastases.

PMID- 15855360
TI  - The Oxford hip scores for primary and revision hip replacement.
AB  - We have used the Oxford hip score to monitor the progress of 1908 primary and 279
      revision hip replacements undertaken since the start of 1995. Our review
      programme began in early 1999 and has generated 3900 assessments. The mean pre
      operative scores for primary and revision cases were 40.95 and 40.11,
      respectively. The mean annual score for primary replacement at between 12 and 84
      months ranged between 20.60 and 22.57. A comparison of cross-sectional and
      longitudinal data showed no significant differences. All post-operative reviews
      showed a significant improvement (p < or = 0.0001). The 50- to 60-year-old group
      scored significantly better than the patients over 80 years of age up to 48
      months (p < 0.01). A subgroup of 826 National Health Service (NHS) and 397
      private patients, treated by the senior author (2292 Oxford assessments), had a
      higher (i.e. worse) mean pre-operative score for the NHS patients (p < or =
      0.001). The private patients scored better than the NHS group up to 84 months (p
      < 0.05). Patients treated by a surgeon performing more than 100 replacements each
      year had a significantly better outcome up to five years than those operated on
      by surgeons performing fewer than 20 replacements each year. The age of the
      patients at the time of operation, and their pre-operative level of disability,
      have both been identified as affecting the long-term outcome. Awareness of the
      influence of these factors should assist surgeons to provide balanced advice.

PMID- 15855361
TI  - Long-term results of the cementless porous-coated anatomic total hip prosthesis.
AB  - Between January 1984 and January 1986, 131 porous-coated anatomic total hip
      replacements were performed in 119 consecutive patients. Of these, 100 patients
      (110 hips) who were alive at a minimum of 18 years after replacement were
      included in the study. The mean age of the patients at surgery was 48.4 years and
      that of surviving patients at the latest follow-up was 67.8 years. The mean
      duration of the clinical and radiological follow-up was 19.4 years (18 to 20).
      The mean Harris hip score initially improved from 55 points before to 95 points
      at two years after operation, but subsequently decreased to 91 points after six
      years, 87 points after 11.2 years, and 85 points after 19.4 years. At the final
      follow-up, 23 hips (18%) of the entire cohort and 21% of survivors had undergone
      revision because of loosening or osteolysis of the acetabular component and eight
      hips (6%) of the entire cohort and 7% of survivors for loosening or osteolysis of
      the femoral component. Only four femoral components (4%) were revised for
      isolated aseptic loosening without osteolysis and two (2%) for recurrent
      dislocation. On the basis of these long-term results, the porous-coated anatomic
      femoral component survived for a minimum of 18 years after operation while the
      acetabular component was less durable. The findings identify the principles of
      uncemented joint replacement which can be applied to current practice.

PMID- 15855362
TI  - Metal ion levels after metal-on-metal proximal femoral replacements: a 30-year
      follow-up.
AB  - Metal-on-metal hip bearings are being implanted into younger patients. The
      consequence of elevated levels of potentially carcinogenic metal ions is
      therefore a cause for concern. We have determined the levels of cobalt (Co),
      chromium (Cr), titanium (Ti) and vanadium (Va) in the urine and whole blood of
      patients who had had metal-on-metal and metal-on-polyethylene articulations in
      situ for more than 30 years. We compared these with each other and with the
      levels for a control group of subjects. We found significantly elevated levels of
      whole blood Ti, Va and urinary Cr in all arthroplasty groups. The whole blood and
      urine levels of Co were grossly elevated, by a factor of 50 and 300 times
      respectively in patients with loose metal-on-metal articulations when compared
      with the control group. Stable metal-on-metal articulations showed much lower
      levels. Elevated levels of whole blood or urinary Co may be useful in identifying
      metal-on-metal articulations which are loose.

PMID- 15855363
TI  - The complications of displaced intracapsular fractures of the hip: the effect of
      screw positioning and angulation on fracture healing.
AB  - We have studied the placement of three screws within the femoral head and the
      degree of angulation of the screws in 395 patients with displaced intracapsular
      fracture of the hip to see if either was related to the risk of failure of the
      fracture to unite. No relationship between nonunion of the fracture was found
      regarding the position of the screws on the anteroposterior radiograph. However,
      we found that a reduced spread of the screws on the lateral view was associated
      with an increased risk of nonunion of the fracture.

PMID- 15855364
TI  - Total hip arthroplasty with a sliding iliac graft for acetabular dysplasia.
AB  - We describe a new technique of reconstruction of the deficient acetabulum in
      cementless total hip arthroplasty. The outer iliac table just above the deficient
      acetabulum is osteotomised and slid downwards. We have termed this an iliac
      sliding graft. Between October 1997 and November 2001, cementless total hip
      arthroplasty with an iliac sliding graft was performed on 19 patients (19 hips)
      with acetabular dysplasia. The mean follow-up was 3.4 years (2 to 6). The mean
      pre-operative Harris hip score was 45.1 which improved significantly to 85.3 at
      the time of the final follow-up. No patient had post-operative abductor
      dysfunction. Incorporation of the graft was seen after two to three months in all
      patients. Resorption of the graft and radiolucencies were infrequent. This
      technique is a useful alternative to femoral head autografting when the patient's
      own femoral head cannot be used.

PMID- 15855365
TI  - Autologous chondrocyte implantation versus matrix-induced autologous chondrocyte
      implantation for osteochondral defects of the knee: a prospective, randomised
      study.
AB  - Autologous chondrocyte implantation (ACI) is used widely as a treatment for
      symptomatic chondral and osteochondral defects of the knee. Variations of the
      original periosteum-cover technique include the use of porcine-derived type
      I/type III collagen as a cover (ACI-C) and matrix-induced autologous chondrocyte
      implantation (MACI) using a collagen bilayer seeded with chondrocytes. We have
      performed a prospective, randomised comparison of ACI-C and MACI for the
      treatment of symptomatic chondral defects of the knee in 91 patients, of whom 44
      received ACI-C and 47 MACI grafts. Both treatments resulted in improvement of the
      clinical score after one year. The mean modified Cincinnati knee score increased
      by 17.6 in the ACI-C group and 19.6 in the MACI group (p = 0.32). Arthroscopic
      assessments performed after one year showed a good to excellent International
      Cartilage Repair Society score in 79.2% of ACI-C and 66.6% of MACI grafts.
      Hyaline-like cartilage or hyaline-like cartilage with fibrocartilage was found in
      the biopsies of 43.9% of the ACI-C and 36.4% of the MACI grafts after one year.
      The rate of hypertrophy of the graft was 9% (4 of 44) in the ACI-C group and 6%
      (3 of 47) in the MACI group. The frequency of re-operation was 9% in each group.
      We conclude that the clinical, arthroscopic and histological outcomes are
      comparable for both ACI-C and MACI. While MACI is technically attractive, further
      long-term studies are required before the technique is widely adopted.

PMID- 15855366
TI  - Kinematics of posterior cruciate ligament-retaining and -substituting total knee
      arthroplasty: a prospective randomised outcome study.
AB  - We performed a prospective, randomised trial of 44 patients to compare the
      functional outcomes of a posterior-cruciate-ligament-retaining and posterior
      cruciate-ligament-substituting total knee arthroplasty, and to gain a better
      understanding of the in vivo kinematic behaviour of both devices. At follow-up at
      five years, no statistically significant differences were found in the clinical
      outcome measurements for either design. The prevalence of radiolucent lines and
      the survivorship were the same. In a subgroup of 15 knees, additional image
      intensifier analysis in the horizontal and sagittal planes was performed during
      step-up and lunge activity. Our analysis revealed striking differences. Lunge
      activity showed a mean posterior displacement of both medial and lateral
      tibiofemoral contact areas (roll-back) which was greater and more consistent in
      the cruciate-substituting than in the cruciate-retaining group (medial p <
      0.0001, lateral p = 0.011). The amount of posterior displacement could predict
      the maximum flexion which could be achieved (p = 0.018). Forward displacement of
      the tibiofemoral contact area in flexion during stair activity was seen more in
      the cruciate-retaining than in the cruciate-substituting group. This was
      attributed mainly to insufficiency of the posterior cruciate ligament and
      partially to that of the anterior cruciate ligament. We concluded that, despite
      similar clinical outcomes, there are significant kinematic differences between
      cruciate-retaining and cruciate-substituting arthroplasties.

PMID- 15855367
TI  - Mechanical testing of impaction bone grafting in the tibia: initial stability and
      design of the stem.
AB  - Clinical experience of impaction bone grafting for revision knee arthroplasty is
      limited, with initial stability of the tibial tray emerging as a major concern.
      The length of the stem and its diameter have been altered to improve stability.
      Our aim was to investigate the effect of the type of stem, support of the rim and
      graft impaction on early stability of the tray. We developed a system for
      impaction grafting of trays which we used with morsellised bone in artificial
      tibiae. Trays with short, long thick or long thin stems were implanted, with or
      without support of the rim. They were cyclically loaded while measuring relative
      movement. Long-stemmed trays migrated 4.5 times less than short-stemmed trays,
      regardless of diameter. Those with support migrated 2.8 times less than those
      without. The migration of short-stemmed trays correlated inversely with the
      density of the impacted groups. That of impaction-grafted tibial trays was in the
      range reported for uncemented primary trays. Movements of short-stemmed trays
      without cortical support were largest and sensitive to the degree of compaction
      of the graft. If support of the rim was sufficient or a long stem was used,
      impacted morsellised bone graft achieved adequate initial stability.

PMID- 15855368
TI  - Palsy of the common peroneal nerve after traumatic dislocation of the knee.
AB  - Injury to the common peroneal nerve was present in 14 of 55 patients (25%) with
      dislocation of the knee. All underwent ligament reconstruction. The most common
      presenting direction of the dislocation was anterior or anteromedial with
      associated disruption of both cruciate ligaments and the posterolateral
      structures of the knee. Palsy of the common peroneal nerve was present in 14 of
      34 (41%) of these patients. Complete rupture of the nerve was seen in four
      patients and a lesion in continuity in ten. Three patients with lesions in
      continuity, but with less than 7 cm of the nerve involved, had complete recovery
      within six to 18 months. In the remaining seven with more extensive lesions, two
      regained no motor function, and one had only MRC grade-2 function. Four patients
      regained some weak dorsiflexion or eversion (MRC grade 3 or 4). Some sensory
      recovery occurred in all seven of these patients, but was incomplete. In summary,
      complete recovery occurred in three (21%) and partial recovery of useful motor
      function in four (29%). In the other seven (50%) no useful motor or sensory
      function returned.

PMID- 15855369
TI  - The proximal extent of the ankle capsule and safety for the insertion of
      percutaneous fine wires.
AB  - We have assessed the proximal capsular extension of the ankle joint in 18
      patients who had a contrast-enhanced MRI ankle arthrogram in order to delineate
      the capsular attachments. We noted consistent proximal capsular extensions
      anterior to the distal tibia and in the tibiofibular recess. The mean capsular
      extension anterior to the distal tibia was 9.6 mm (4.9 to 27.0) proximal to the
      anteroinferior tibial margin and 3.8 mm (-2.1 to 9.3) proximal to the dome of the
      tibial plafond. In the tibiofibular recess, the mean capsular extension was 19.2
      mm (12.7 to 38.0) proximal to the anteroinferior tibial margin and 13.4 mm (5.8
      to 20.5) proximal to the dome of the tibial plafond. These areas of proximal
      capsular extensions run the risk of being traversed during the insertion of
      finewires for the treatment of fractures of the distal tibia. Surgeons using
      these techniques should be aware of this anatomy in order to minimise the risk of
      septic arthritis.

PMID- 15855370
TI  - Shoulder hemiarthroplasty in patients with juvenile idiopathic arthritis.
AB  - Replacement of the shoulder in juvenile idiopathic arthritis is not often
      performed and there have been no published series to date. We present nine
      glenohumeral hemiarthroplasties in eight patients with systemic or polyarticular
      juvenile idiopathic arthritis. The mean follow-up was six years (59 to 89
      months). The mean age at the time of surgery was 32 years. Surgery took place at
      a mean of 27 years after diagnosis. The results indicated excellent relief from
      pain. There was restoration of useful function which deteriorated with time, in
      part because of progression of the systemic disease in this severely affected
      group. No patient has required revision to date and there has been no
      radiological evidence of loosening or osteolysis around the implants. We discuss
      the pathoanatomical challenges unique to this group. There was very little space
      for a prosthetic joint and, in some cases, bony deformity and the small size
      necessitated the use of custom-made implants.

PMID- 15855371
TI  - Criteria for arthroscopic treatment of anterior instability of the shoulder: a
      prospective study.
AB  - We prospectively evaluated 61 patients treated arthroscopically for anterior
      instability of the shoulder at a mean follow-up of 44.5 months (24 to 100) using
      the Rowe scale. Those with post-operative dislocation or subluxation were
      considered to be failures. Logistic regression analysis was used to identify
      patients at increased risk of recurrence in order to develop a suitable selection
      system. The mean Rowe score improved from 45 pre-operatively to 86 at follow-up
      (p < 0.001). At least one episode of post-operative instability occurred in 11
      patients (18%), although their stability improved (p = 0.018), and only three
      required revision. Subjectively, eight patients were dissatisfied. Age younger
      than 28 years, ligamentous laxity, the presence of a fracture of the glenoid rim
      involving more than 15% of the articular surface, and post-operative
      participation in contact or overhead sports were associated with a higher risk of
      recurrence, and scored 1, 1, 5 and 1 point, respectively. Those patients with a
      total score of two or more points had a relative risk of recurrence of 43% and
      should be treated by open surgery.

PMID- 15855372
TI  - The detection of loose bodies in the elbow: the value of MRI and CT arthrography.
AB  - Our aim was to determine the clinical value of MRI and CT arthrography in
      predicting the presence of loose bodies in the elbow. A series of 26 patients
      with mechanical symptoms in the elbow had plain radiography, MRI and CT
      arthrography, followed by routine arthroscopy of the elbow. The location and
      number of loose bodies determined by MRI and CT arthrography were recorded. Pre
      operative plain radiography, MRI and CT arthrography were compared with
      arthroscopy. Both MRI and CT arthrography had excellent sensitivity (92% to 100%)
      but low to moderate specificity (15% to 77%) in identifying posteriorly-based
      loose bodies. Neither MRI nor CT arthrography was consistently sensitive (46% to
      91%) or specific (13% to 73%) in predicting the presence or absence of loose
      bodies anteriorly. The overall sensitivity for the detection of loose bodies in
      either compartment was 88% to 100% and the specificity 20% to 70%. Pre-operative
      radiography had a similar sensitivity and specificity of 84% and 71%,
      respectively. Our results suggest that neither CT arthrography nor MRI is
      reliable or accurate enough to be any more effective than plain radiography alone
      in patients presenting with mechanical symptoms in the elbow.

PMID- 15855373
TI  - Intervertebral disc degeneration associated with lumbosacral transitional
      vertebrae: a clinical and anatomical study.
AB  - We studied 52 patients, each with a lumbosacral transitional vertebra. Using MRI
      we found that the lumbar discs immediately above the transitional vertebra were
      significantly more degenerative and those between the transitional vertebrae and
      the sacrum were significantly less degenerative compared with discs at other
      levels. We also performed an anatomical study using 70 cadavers. We found that
      the iliolumbar ligament at the level immediately above the transitional vertebra
      was thinner and weaker than it was in cadavers without a lumbosacral transitional
      vertebra. Instability of the vertebral segment above the transitional vertebra
      because of a weak iliolumbar ligament could lead to subsequent disc degeneration
      which may occur earlier than at other disc levels. Some stability between the
      transitional vertebra and the sacrum could be preserved by the formation of
      either an articulation or by bony union between the vertebra and the sacrum
      through its transverse process. This may protect the disc from further
      degeneration in the long term.

PMID- 15855374
TI  - Anatomy of pilon fractures of the distal tibia.
AB  - In a series of 126 consecutive pilon fractures, we have described anatomically
      explicable fragments. Fracture lines describing these fragments have revealed ten
      types of pilon fracture which belong to two families, sagittal and coronal. The
      type of fracture is dictated by the energy of injury, the direction of the force
      of injury and the age of the patient.

PMID- 15855375
TI  - Prognostic factors and a scoring system for patients with skeletal metastasis.
AB  - Between 1992 and 1999, we treated 350 patients with skeletal metastases. A
      multivariable analysis of the patients was conducted using the Cox proportional
      hazards model. We identified five significant prognostic factors for survival,
      namely, the site of the primary lesion, the performance status (Eastern
      Cooperative Oncology Group status 3 or 4), the presence of visceral or cerebral
      metastases, any previous chemotherapy, and multiple skeletal metastases. The
      score for each significant factor was derived from the corresponding estimated
      regression coefficients (natural logarithm of the hazard ratio). The prognostic
      score was calculated by adding all the scores for individual factors. The rate of
      survival was 31% at six months and 11% at one year for the patients with a
      prognostic score of 6 or more. By contrast, patients with a prognostic score of 2
      or less had a rate of survival of 98% at six months and 89% at one year. This
      scoring system can be used to determine the optimal treatment for patients with
      pathological fractures or epidural compression.

PMID- 15855376
TI  - Reconstruction after intercalary resection of malignant bone tumours: comparison
      between segmental allograft and extracorporeally-irradiated autograft.
AB  - We reviewed 29 patients who had undergone intercalary resection for malignant
      tumours. Of these, 14 had received segmental allograft reconstruction and 15
      extracorporeally-irradiated autograft. At a mean follow-up of 71 months (24 to
      132), 20 were free from disease, five had died and four were alive with pulmonary
      metastases. Two patients, one with an allograft and one with an irradiated
      autograft, had a local recurrence. Reconstruction with extracorporeally
      irradiated autograft has a significantly lower rate of nonunion (7% vs 43%, p =
      0.031) but an insignificantly higher rate of fracture (20% vs 14%, p = 0.535)
      than that with segmental allograft. Using the Enneking functional evaluation
      system, the mean postoperative score for the patients without local recurrence
      was 87% (80% to 96%) and was similar in both groups. Extracorporeally-irradiated
      autograft could be an acceptable alternative for reconstruction after intercalary
      resection, especially in countries where it is difficult to obtain allografts.

PMID- 15855377
TI  - Double-elevating osteotomy for late-presenting infantile Blount's disease: the
      importance of concomitant lateral epiphysiodesis.
AB  - We reviewed 34 knees in 24 children after a double-elevating osteotomy for late
      presenting infantile Blount's disease. The mean age of patients was 9.1 years (7
      to 13.5). All knees were in Langenskiold stages IV to VI. The operative technique
      corrected the depression of the medial joint line by an elevating osteotomy, and
      the remaining tibial varus and internal torsion by an osteotomy just below the
      apophysis. In the more recent patients (19 knees), a proximal lateral tibial
      epiphysiodesis was performed at the same time. The mean pre-operative angle of
      depression of the medial tibial plateau of 49 degrees (40 degrees to 60 degrees )
      was corrected to a mean of 26 degrees (20 degrees to 30 degrees ), which was
      maintained at follow-up. The femoral deformity was too small to warrant femoral
      osteotomy in any of our patients. The mean pre-operative mechanical varus of 30.6
      degrees (14 degrees to 66 degrees ) was corrected to 0 degrees to 5 degrees of
      mechanical valgus in 29 knees. In five knees, there was an undercorrection of 2
      degrees to 5 degrees of mechanical varus. At follow-up a further eight knees, in
      which lateral epiphysiodesis was delayed beyond five months, developed recurrent
      tibial varus associated with fusion of the medial proximal tibial physis.

PMID- 15855378
TI  - The care of pin sites with external fixation.
AB  - Two protocols for the operative technique and care of the pin-site with external
      fixation were compared prospectively. There was a total of 120 patients with 46
      in group A and 74 in group B. Infection was defined as an episode of pain or
      inflammation at a pin site, accompanied by a discharge which was either positive
      on bacterial culture or responded to a course of antibiotics. Patients in group B
      had a lower proportion of infected pin sites (p = 0.003) and the time to the
      first episode of infection was longer (p < 0.001). The risk of pin-site infection
      is lower if attention is paid to avoiding thermal injury and local formation of
      haematoma during surgery and if after-care includes the use of an alcoholic
      antiseptic and occlusive pressure dressings.

PMID- 15855379
TI  - Repair of large full-thickness articular cartilage defects in the rabbit: the
      effects of joint distraction and autologous bone-marrow-derived mesenchymal cell
      transplantation.
AB  - We produced large full-thickness articular cartilage defects in 33 rabbits in
      order to evaluate the effect of joint distraction and autologous culture-expanded
      bone-marrow-derived mesenchymal cell transplantation (ACBMT) at 12 weeks. After
      fixing the knee on a hinged external fixator, we resected the entire surface of
      the tibial plateau. We studied three groups: 1) with and without joint
      distraction; 2) with joint distraction and collagen gel, and 3) with joint
      distraction and ACBMT and collagen gel. The histological scores were
      significantly higher in the groups with ACBMT collagen gel (p < 0.05). The area
      of regenerated soft tissue was smaller in the group allowed to bear weight (p <
      0.05). These findings suggest that the repair of large defects of cartilage can
      be enhanced by joint distraction, collagen gel and ACBMT.

PMID- 15855380
TI  - The treatment of osteochondral lesions using a combination of autologous
      chondrocyte implantation and autograft: three-year follow-up.
AB  - In this study a combination of autologous chondrocyte implantation (ACI) and the
      osteochondral autograft transfer system (OATS) was used and evaluated as a
      treatment option for the repair of large areas of degenerative articular
      cartilage. We present the results at three years post-operatively. Osteochondral
      cores were used to restore the contour of articular cartilage in 13 patients with
      large lesions of the lateral femoral condyle (n = 5), medial femoral condyle (n =
      7) and patella (n = 1). Autologous cultured chondrocytes were injected underneath
      a periosteal patch covering the cores. After one year, the patients had a
      significant improvement in their symptoms and after three years this level of
      improvement was maintained in ten of the 13 patients. Arthroscopic examination
      revealed that the osteochondral cores became well integrated with the surrounding
      cartilage. We conclude that the hybrid ACI/OATS technique provides a promising
      surgical approach for the treatment of patients with large degenerative
      osteochondral defects.

PMID- 15855381
TI  - The effect of accuracy of implantation on range of movement of the Scandinavian
      Total Ankle Replacement.
AB  - When performing the Scandinavian Total Ankle Replacement (STAR), the positioning
      of the talar component and the selection of mobile-bearing thickness are
      critical. A biomechanical experiment was undertaken to establish the effects of
      these variables on the range of movement (ROM) of the ankle. Six cadaver ankles
      containing a specially-modified STAR prosthesis were subjected to ROM
      determination, under weight-bearing conditions, while monitoring the strain in
      the peri-ankle ligaments. Each specimen was tested with the talar component
      positions in neutral, as well as 3 and 6 mm of anterior and posterior
      displacement. The sequence was repeated with an anatomical bearing thickness, as
      well as at 2 mm reduced and increased thicknesses. The movement limits were
      defined as 10% strain in any ligament, bearing lift-off from the talar component
      or limitations of the hardware. Both anterior talar component displacement and
      bearing thickness reduction caused a decrease in plantar flexion, which was
      associated with bearing lift-off. With increased bearing thickness, posterior
      displacement of the talar component decreased plantar flexion, whereas anterior
      displacement decreased dorsiflexion.

PMID- 15855382
TI  - EBRA-FCA for measurement of migration of the femoral component in surface
      arthroplasty of the hip.
AB  - Studies on the migration of an implant may be the only way of monitoring the
      early performance of metal-on-metal prostheses. The Ein Bild Roentgen Analyse-
      femoral component analysis (EBRA-FCA) method was adapted to measure migration of
      the femoral component in a metal-on-metal surface arthroplasty of the hip using
      standard antero-posterior radiographs. In order to determine the accuracy and
      precision of this method a prosthesis was implanted into cadaver bones. Eleven
      series of radiographs were used to perform a zero-migration study. After
      adjustment of the femoral component to simulate migration of 3 mm the radiographs
      were repeated. All were measured independently by three different observers. The
      accuracy of the method was found to be +/- 1.6 mm for the x-direction and +/- 2
      mm for the y-direction (95% percentile). The method was validated using 28 hips
      with a minimum follow-up of 3.5 years after arthroplasty. Seventeen were sound,
      but 11 had failed because of loosening of the femoral component. The normal
      (control) group had a different pattern of migration compared with that of the
      loose group. At 29.2 months, the control group showed a mean migration of 1.62 mm
      and 1.05 mm compared with 4.39 mm and 4.05 mm in the failed group, for the centre
      of the head and the tip of the stem, respectively (p = 0.001). In the failed
      group, the mean time to migration greater than 2 mm was earlier than the onset of
      clinical symptoms or radiological evidence of failure, 19.1 versus 32.2 months (p
      = 0.001) and 24.8 months (p = 0.012), respectively. EBRA-FCA is a reliable and
      valid tool for measuring migration of the femoral component after surface
      arthroplasty and can be used to predict early failure of the implant. It may be
      of value in determining the long-term performance of surface arthroplasty.

PMID- 15855383
TI  - Pain in the well-fixed, aseptic titanium hip replacement: the role of corrosion.

PMID- 15855385
TI  - Influence of genetic background on daily running-wheel activity differs with
      aging.
AB  - In humans, physical activity declines with age. We tested the hypothesis that
      genetic background and age interact to determine daily wheel-running physical
      activity patterns in mice. Five female mice from ten inbred strains (A/J, AKR/J,
      Balb/cJ, CBA/J, C3H/HeJ, C3Heb/FeJ, C57Bl/6J, C57L/J, DBA/2J, and SWR/J) were
      studied for 26 wk starting at 10 wk of age. All mice were housed in separate
      cages, each with a running wheel and magnetic sensor. Throughout the 26-wk
      period, age-related change in daily duration (P < 0.0001), daily distance (P <
      0.0001), and average velocity (P = 0.0003) differed between the inbred strains.
      Unlike the other strains, SWR/J mice increased their running-wheel activity
      throughout the 6-mo time period. Broad-sense heritability estimations for the
      strains across the 26-wk period ranged between 0.410 and 0.855 for the three
      physical activity phenotypes. Furthermore, the broad-sense heritability estimates
      for daily running-wheel distance differed across time and suggested an
      interaction between genetic background and age on physical activity in these
      inbred mice.

PMID- 15855386
TI  - Genome-wide survey of V-ATPase genes in Drosophila reveals a conserved renal
      phenotype for lethal alleles.
AB  - V-ATPases are ubiquitous, vital proton pumps that play a multiplicity of roles in
      higher organisms. In many epithelia, they are the major energizer of cotransport
      processes and have been implicated in functions as diverse as fluid secretion and
      longevity. The first animal knockout of a V-ATPase was identified in Drosophila,
      and its recessive lethality demonstrated the essential nature of V-ATPases. This
      article surveys the entire V-ATPase gene family in Drosophila, both
      experimentally and in silico. Adult expression patterns of most of the genes are
      shown experimentally for the first time, using in situ hybridization or reporter
      gene expression, and these results are reconciled with published expression and
      microarray data. For each subunit, the single gene identified previously by
      microarray, as upregulated and abundant in tubules, is shown to be similarly
      abundant in other epithelia in which V-ATPases are known to be important; there
      thus appears to be a single dominant "plasma membrane" V-ATPase holoenzyme in
      Drosophila. This provides the most comprehensive view of V-ATPase expression yet
      in a multicellular organism. The transparent Malpighian tubule phenotype first
      identified in lethal alleles of vha55, the gene encoding the B-subunit, is shown
      to be general to those plasma membrane V-ATPase subunits for which lethal alleles
      are available, and to be caused by failure to accumulate uric acid crystals.
      These results coincide with the expression view of the gene family, in which 13
      of the genes are specialized for epithelial roles, whereas others have spatially
      or temporally restricted patterns of expression.

PMID- 15855387
TI  - Definition of the unique human extraocular muscle allotype by expression
      profiling.
AB  - The extraocular muscles (EOMs) are a unique group of specialized muscles that are
      anatomically and physiologically distinct from other skeletal muscles. Perhaps
      the most striking characteristic of the EOMs is their differential sensitivity to
      disease. EOMs are spared in Duchenne's muscular dystrophy (DMD) despite
      widespread involvement of other skeletal muscles. Conversely, they are early and
      prominent targets in myasthenia gravis and mitochondrial myopathies. It is
      unclear how EOMs achieve such specialization or a differential response to
      diseases; however, this has been attributed to a unique, group-specific pattern
      of gene expression or "allotype." To begin to address these issues as well as
      define the human EOM allotype, we analyzed the human EOM transcriptome using
      oligonucleotide-based expression profiling. Three hundred thirty-eight genes were
      found to be differentially expressed in EOM compared with quadriceps femoris limb
      muscle, using a twofold cutoff. Functional characterization revealed expression
      patterns corresponding to known metabolic and structural properties of EOMs such
      as expression of EOM-specific myosin heavy chain (MYH13) and high neural,
      vascular, and mitochondrial content, suggesting that the profiling was sensitive
      and specific. Genes related to myogenesis, stem cells, and apoptosis were
      detected at high levels in normal human EOMs, suggesting that efficient and
      continuous regeneration and/or myogenesis may be a mechanism by which the EOMs
      remain clinically and pathologically spared in diseases such as DMD. Taken
      together, this study provides insight into how human EOMs achieve their unique
      structural, metabolic, and pathophysiological properties.

PMID- 15855388
TI  - Scaling functions to body size: theories and facts.

PMID- 15855389
TI  - The origin of allometric scaling laws in biology from genomes to ecosystems:
      towards a quantitative unifying theory of biological structure and organization.
AB  - Life is the most complex physical phenomenon in the Universe, manifesting an
      extraordinary diversity of form and function over an enormous scale from the
      largest animals and plants to the smallest microbes and subcellular units.
      Despite this many of its most fundamental and complex phenomena scale with size
      in a surprisingly simple fashion. For example, metabolic rate scales as the 3/4
      power of mass over 27 orders of magnitude, from molecular and intracellular
      levels up to the largest organisms. Similarly, time-scales (such as lifespans and
      growth rates) and sizes (such as bacterial genome lengths, tree heights and
      mitochondrial densities) scale with exponents that are typically simple powers of
      1/4. The universality and simplicity of these relationships suggest that
      fundamental universal principles underly much of the coarse-grained generic
      structure and organisation of living systems. We have proposed a set of
      principles based on the observation that almost all life is sustained by
      hierarchical branching networks, which we assume have invariant terminal units,
      are space-filling and are optimised by the process of natural selection. We show
      how these general constraints explain quarter power scaling and lead to a
      quantitative, predictive theory that captures many of the essential features of
      diverse biological systems. Examples considered include animal circulatory
      systems, plant vascular systems, growth, mitochondrial densities, and the concept
      of a universal molecular clock. Temperature considerations, dimensionality and
      the role of invariants are discussed. Criticisms and controversies associated
      with this approach are also addressed.

PMID- 15855390
TI  - Membranes and the setting of energy demand.
AB  - In his classic 1961 book, The Fire of Life, Max Kleiber presented a critique of
      the theories advanced to explain the BMR-body size relationship. One of the
      theories he dismissed was that the chemical composition of animals varies with
      body size. Since this time, however, much has been learned about the make-up of
      BMR in different animals as well as the chemical composition of different-sized
      animals. Specifically, in recent years it has become obvious that mammal species
      and bird species do vary in chemical composition in a systematic manner
      associated with the body size of the species. Small mammal and bird species have
      cellular membranes that are predominantly polyunsaturated, and as mammal and bird
      species increase in size, their cellular membranes become progressively less
      polyunsaturated. Since Kleiber's time, it has also become obvious that a
      substantial amount of the energy turnover of BMR is associated with the activity
      of membrane processes, specifically the maintenance of trans-membrane gradients,
      such as the Na+ gradient across the plasmalemmal membrane and the H+ gradient
      across the mitochondrial inner membrane. The variation in both membrane
      composition and membrane processes associated with body size variation in
      metabolic rate has been combined in the 'membrane pacemaker' theory of
      metabolism. This theory proposes that: (1) membrane-associated activities are
      significant and dominant components of BMR; (2) when BMR varies among species,
      all the activities that constitute BMR vary in unison; (3) species with high mass
      specific BMR have highly polyunsaturated membranes while those with low BMR have
      less polyunsaturation of their membranes; (4) highly polyunsaturated membranes
      have distinctive physical properties that cause the proteins in the membranes to
      have a high molecular activity, and this results in higher rates of metabolism of
      cells, tissues and, consequently, the whole animal. Evidence supporting this
      theory is both correlative and experimental. Manipulation of membrane composition
      changes the molecular activity of membrane proteins. These differences in
      membrane composition may also represent a link between metabolism and aging. They
      probably explain the lifespan-body size relationship in mammals and birds and
      also the mammal-bird difference in lifespan.

PMID- 15855391
TI  - Control of muscle bioenergetic gene expression: implications for allometric
      scaling relationships of glycolytic and oxidative enzymes.
AB  - Muscle metabolic properties vary with body size, with larger animals relying
      relatively less on oxidative metabolism as a result of lower specific activities
      of mitochondrial enzymes and greater specific activities of glycolytic enzymes.
      While many have argued reasons why such relationships might be grounded in
      physical relationships, an explanation for the regulatory basis of the
      differences in enzyme levels remains unexplored. Focusing on skeletal muscle, we
      review potential cellular and genetic explanations for the relationship between
      bioenergetic enzymes and body mass. Differences in myonuclear domain (the ratio
      of fiber volume to nuclei number) in conjunction with constitutive expression may
      explain part of the variation in mitochondrial content among fiber types and
      species. Superimposed on such constitutive determinants are (1) extrinsic
      signalling pathways that control the muscle contractile and metabolic phenotype
      and (2) intrinsic signalling pathways that translate changes in cellular milieu
      (ions, metabolites, oxygen, redox) arising through the contractile phenotype into
      changes in enzyme synthesis. These signalling pathways work through
      transcriptional regulation, as well as post-transcriptional, translational and
      post-translational regulation, acting via synthesis and degradation.

PMID- 15855392
TI  - Allometric scaling of mammalian metabolism.
AB  - The importance of size as a determinant of metabolic rate (MR) was first
      suggested by Sarrus and Rameaux over 160 years ago. Max Rubner's finding of a
      proportionality between MR and body surface area in dogs (in 1883) was consistent
      with Sarrus and Rameaux's formulation and suggested a proportionality between MR
      and body mass (Mb) raised to the power of 2/3. However, interspecific analyses
      compiled during the first half of the 20th century concluded that mammalian basal
      MR (BMR, ml O2 h(-1)) was proportional to Mb3/4, a viewpoint that persisted for
      seven decades, even leading to its common application to non-mammalian groups.
      Beginning in 1997, the field was re-invigorated by three new theoretical
      explanations for 3/4-power BMR scaling. However, the debate over which theory
      accurately explains 3/4-power scaling may be premature, because some authors
      maintain that there is insufficient evidence to adopt an exponent of 3/4 over
      2/3. If progress toward understanding the non-isometric scaling of BMR is ever to
      be made, it is first essential to know what the relationship actually is. We re
      examine previous investigations of BMR scaling by standardising units and
      recalculating regression statistics. The proportion of large herbivores in a data
      set is positively correlated both with the scaling exponent (b, where BMR=aMb b)
      and the coefficient of variation (CV: the standard deviation of ln-ln residuals)
      of the relationship. Inclusion of large herbivores therefore both inflates b and
      increases variation around the calculated trendline. This is related to the long
      fast duration required to achieve the postabsorptive conditions required for
      determination of BMR, and because peak post-feeding resting MR (RMRpp) scales
      with an exponent of 0.75+/-0.03 (95% CI). Large herbivores are therefore less
      likely to be postabsorptive when MR is measured, and are likely to have a
      relatively high MR if not postabsorptive. The 3/4 power scaling of RMRpp is part
      of a wider trend where, with the notable exception of cold-induced maximum MR
      (b=0.65+/-0.05), b is positively correlated with the elevation of the
      relationship (higher MR values scale more steeply). Thus exercise-induced maximum
      MR (b=0.87+/-0.05) scales more steeply than RMRpp, field MR (b=0.73+/-0.04),
      thermoneutral resting MR (RMRt, b=0.712+/-0.013) and BMR. The implication of this
      observation is that contamination of BMR data with non-basal measurements is
      likely to increase the BMR scaling exponent even if the contamination is randomly
      distributed with respect to Mb. Artificially elevated scaling exponents can
      therefore be accounted for by the inclusion of measurements that fail to satisfy
      the requirements for basal metabolism, which are strictly defined (adult, non
      reproductive, postabsorptive animals resting in a thermoneutral environment
      during the inactive circadian phase). Similarly, a positive correlation between
      Mb and body temperature (Tb) and between Tb and mass-independent BMR contributes
      to elevation of b. While not strictly a defined condition for the measurement of
      BMR, the normalisation of BMR measurements to a common Tb (36.2 degrees C) to
      achieve standard metabolic rate (SMR) further reduces the CV of the relationship.
      Clearly the value of the exponent depends on the conditions under which the data
      are selected. The exponent for true BMR is 0.686 (+/-0.014), Tb normalised SMR is
      0.675 (+/-0.013) and RMRt is 0.712 (+/-0.013).

PMID- 15855393
TI  - Field metabolic rate and body size.
AB  - The field metabolic rates (FMRs) of 229 species of terrestrial vertebrates, all
      measured using the doubly labeled water method in free-living individuals, were
      evaluated. Daily rates of energy expenditure were as low as 0.23 kJ per day in a
      small reptile (gecko), to as high as 52 500 kJ per day in a marine mammal (seal).
      This is a range of nearly six orders of magnitude. More than 70% of the variation
      in log-transformed data is due to variation in body size (expressed as body
      mass). Much of the remaining variation is accounted for by thermal physiology,
      with the endothermic mammals and birds having FMRs that are about 12 and 20 times
      higher, respectively, than FMRs of equivalent-sized, but ectothermic, reptiles.
      Variation in log(body mass) within each of these three taxonomic classes accounts
      for over 94% of the variation in log(FMR), and results from nonlinear regression
      analyses using untransformed data support this conclusion. However, the range of
      residual variation in mass-adjusted FMR within classes is still more than sixfold
      (ratio of highest over lowest). Some of this variation is associated with
      affiliations with lower taxonomic levels (Infraclass: eutherian vs metatherian
      mammals; Family: passerine, procellariform and galliform birds vs other birds),
      some is associated with habitat (especially desert vs nondesert), and some with
      differences in basic diet preference and foraging mode and season. The scaling
      slopes for FMR often differ from BMR slopes for the same Class of animals, and
      most differ from the theoretical slope of 0.75. Differences among slopes and
      intercepts that were detected using conventional regression analyses were largely
      confirmed upon reanalysis using Independent Contrasts Analysis to adjust for
      phylogenetic biases.

PMID- 15855394
TI  - Multi-level regulation and metabolic scaling.
AB  - Metabolic control analysis has revealed that flux through pathways is the
      consequence of system properties, i.e. shared control by multiple steps, as well
      as the kinetic effects of various pathways and processes over each other. This
      implies that the allometric scaling of flux rates must be understood in terms of
      properties that pertain to the regulation of flux rates. In contrast, proponents
      of models considering the scaling of branching or fractal-like systems suggest
      that supply rates determine metabolic rates. Therefore, the allometric scaling of
      supply alone provides a sufficient explanation for the allometric scaling of
      metabolism. Examination of empirical data from the literature of comparative
      physiology reveals that basal metabolic rates (BMR) are driven by rates of energy
      expenditure within internal organs and that the allometric scaling of BMR can be
      understood in terms of the scaling of the masses and metabolic rates of internal
      organs. Organ metabolic rates represent the sum of tissue metabolic rates while,
      within tissues, cellular metabolic rates are the outcome of shared regulation by
      multiple processes. Maximal metabolic rates (MMR, measured as maximum rates of O2
      consumption, VO2max) during exercise also scale allometrically, are also subject
      to control by multiple processes, but are due mainly to O2 consumption by
      locomotory muscles. Thus, analyses of the scaling of MMR must consider the
      scaling of both muscle mass and muscle energy expenditure. Consistent with the
      principle of symmorphosis, allometry in capacities for supply (the outcome of
      physical design constraints) is observed to be roughly matched by allometry in
      capacities for demand (i.e. for energy expenditure). However, physiological rates
      most often fall far below maximum capacities and are subject to multi-step
      regulation. Thus, mechanistic explanations for the scaling of BMR and MMR must
      consider the manner in which capacities are matched and how rates are regulated
      at multiple levels of biological organization.

PMID- 15855395
TI  - Exercise-induced maximal metabolic rate scales with muscle aerobic capacity.
AB  - The logarithmic nature of the allometric equation suggests that metabolic rate
      scaling is related to some fractal properties of the organism. Two universal
      models have been proposed, based on (1) the fractal design of the vasculature and
      (2) the fractal nature of the 'total effective surface' of mitochondria and
      capillaries. According to these models, basal and maximal metabolic rates must
      scale as M3/4. This is not what we find. In 34 eutherian mammalian species (body
      mass Mb ranging from 7 g to 500 kg) we found VO2max to scale with the 0.872 (+/
      0.029) power of body mass, which is significantly different from 3/4 power
      scaling. Integrated structure-function studies on a subset of eleven species (Mb
      20 g to 450 kg) show that the variation of VO2max with body size is tightly
      associated with the total volume of mitochondria and of the locomotor musculature
      capillaries. In athletic species the higher VO2max is linked to proportionally
      larger mitochondrial and capillary volumes. As a result, VO2max is linearly
      related to both total mitochondrial and capillary erythrocyte volumes, as well as
      to their surface areas. Consequently, the allometric variation of maximal
      metabolic rate is directly related to the scaling of the total effective surfaces
      of mitochondria and capillaries, thus confirming the basic conjecture of the
      second fractal models but refuting the arguments for 3/4 power scaling. We
      conclude that the scaling of maximal metabolic rate is determined by the energy
      needs of the cells active during maximal work. The vascular supply network is
      adapted to the needs of the cells at their working limit. We conjecture that the
      optimization of the arterial tree by fractal design is the result rather than the
      cause of the evolution of metabolic rate scaling. The remaining question is why
      the energy needs of locomotion scale with the 0.872 or 7/8 power of body mass.

PMID- 15855396
TI  - Models and the scaling of energy costs for locomotion.
AB  - To achieve the required generality, models designed to predict scaling
      relationships for diverse groups of animals generally need to be simple. An
      argument based on considerations of dynamic similarity predicts correctly that
      the mechanical cost of transport for running [power/(body mass x speed)] will be
      independent of body mass; but measurements of oxygen consumption for running
      birds and mammals show that the metabolic cost of transport is proportional to
      (body mass)-0.32. Thus the leg muscles seem to work more efficiently in larger
      animals. A model that treats birds as fixed wing aircraft predicts that the
      mechanical power required for flight at the maximum range speed will be
      proportional to (body mass)1.02, but the metabolic power is found to be
      proportional to (body mass)0.83; again, larger animals seem to have more
      efficient muscles. A model that treats hovering hummingbirds and insects as
      helicopters predicts mechanical power to be approximately proportional to body
      mass, but measurements of oxygen consumption once again show efficiency
      increasing with body mass. A model of swimming fish as rigid submarines predicts
      power to be proportional to (body mass)0.5 x (speed)2.5 or to (body mass)0.6 x
      (speed)2.8, depending on whether flow in the boundary layer is laminar or
      turbulent. Unfortunately, this prediction cannot easily be compared with
      available compilations of metabolic data. The finding that efficiency seems to
      increase with body mass, at least in running and flight, is discussed in relation
      to the metabolic energy costs of muscular work and force.

PMID- 15855397
TI  - Scaling of maximum net force output by motors used for locomotion.
AB  - Biological and engineered motors are surprisingly similar in their adherence to
      two or possibly three fundamental regimes for the mass scaling of maximum force
      output (Fmax). One scaling regime (Group 1: myosin, kinesin, dynein and RNA
      polymerase molecules; muscle cells; whole muscles; winches; linear actuators)
      comprises motors that create slow translational motion with force outputs limited
      by the axial stress capacity of the motor, which results in Fmax scaling as motor
      mass0.67 (M0.67). Another scaling regime (Group 2: flying birds, bats and
      insects; swimming fish; running animals; piston engines; electric motors; jets)
      comprises motors that cycle rapidly, with significant internal and external
      accelerations, and for whom inertia and fatigue life appear to be important
      constraints. The scaling of inertial loads and fatigue life both appear to
      enforce Fmax scaling as M1.0 in these motors. Despite great differences in
      materials and mechanisms, the mass specific Fmax of Group 2 motors clusters
      tightly around a mean of 57 N kg(-1), a region of specific force loading where
      there appears to be a common transition from high- to low-cycle fatigue. For
      motors subject to multi-axial stresses, the steepness of the load-life curve in
      the neighborhood of 50-100 N kg(-1) may overwhelm other material and mechanistic
      factors, thereby homogenizing the mass specific Fmax of grossly dissimilar
      animals and machines. Rockets scale with Group 1 motors but for different
      mechanistic reasons; they are free from fatigue constraints and their thrust is
      determined by mass flow rates that depend on cross sectional area of the exit
      nozzle. There is possibly a third scaling regime of Fmax for small motors
      (bacterial and spermatazoan flagella; a protozoan spring) where viscosity
      dominates over inertia. Data for force output of viscous regime motors are
      scarce, but the few data available suggest a gradually increasing scaling slope
      that converges with the Group 2 scaling relationship at a Reynolds number of
      about 10(2). The Group 1 and Group 2 scaling relationships intersect at a motor
      mass of 4400 kg, which restricts the force output and design of Group 2 motors
      greater than this mass. Above 4400 kg, all motors are limited by stress and have
      Fmax that scales as M0.67; this results in a gradual decline in mass specific
      Fmax at motor mass greater than 4400 kg. Because of declining mass specific Fmax,
      there is little or no potential for biological or engineered motors or rockets
      larger than those already in use.

PMID- 15855398
TI  - Biomechanical consequences of scaling.
AB  - To function over a lifetime of use, materials and structures must be designed to
      have sufficient factors of safety to avoid failure. Vertebrates are generally
      built from materials having similar properties. Safety factors are most commonly
      calculated based on the ratio of a structure's failure stress to its peak
      operating stress. However, yield stress is a more likely limit, and work of
      fracture relative to energy absorption is likely the most relevant measure of a
      structure's safety factor, particularly under impact loading conditions
      characteristic of locomotion. Yet, it is also the most difficult to obtain. For
      repeated loading, fatigue damage and eventual failure may be critical to the
      design of biological structures and will result in lower safety factors. Although
      area:volume scaling predicts that stresses will increase with size, interspecific
      comparisons of mammals and birds show that skeletal allometry is modest, with
      most groups scaling (l proportional, variant d0.89) closer to geometric
      similarity (isometry: l proportional, variant d1.0) than to elastic similarity (l
      proportional, variant d0.67) or stress similarity (l proportional, variant d0.5).
      To maintain similar peak bone and muscle stresses, terrestrial mammals change
      posture when running, with larger mammals becoming more erect. More erect limbs
      increases their limb muscle mechanical advantage (EMA) or ratio of ground impulse
      to muscle impulse (r/R= integral G/integral Fm). The increase in limb EMA with
      body weight (proportional, variant W0.25) allows larger mammals to match changes
      in bone and muscle area (proportional, variant W0.72-0.80) to changes in muscle
      force generating requirements (proportional, variantW0.75), keeping bone and
      muscle stresses fairly constant across a size range 0.04-300 kg. Above this size,
      extremely large mammals exhibit more pronounced skeletal allometry and reduced
      locomotor ability. Patterns of ontogenetic scaling during skeletal growth need
      not follow broader interspecific scaling patterns. Instead, negative allometric
      growth (becoming more slender) is often observed and may relate to maturation of
      the skeleton's properties or the need for younger animals to move at faster
      speeds compared with adults. In contrast to bone and muscle stress patterns,
      selection for uniform safety factors in tendons does not appear to occur. In
      addition to providing elastic energy savings, tendons transmit force for control
      of motion of more distal limb segments. Their role in elastic savings requires
      that some tendons operate at high stresses (and strains), which compromises their
      safety factor. Other 'low stress' tendons have larger safety factors, indicating
      that their primary design is for stiffness to reduce the amount of stretch that
      their muscles must overcome when contracting to control movement.

PMID- 15855399
TI  - The constructal law of organization in nature: tree-shaped flows and body size.
AB  - The constructal law is the statement that for a flow system to persist in time it
      must evolve in such a way that it provides easier access to its currents. This is
      the law of configuration generation, or the law of design. The theoretical
      developments reviewed in this article show that this law accounts for (i)
      architectures that maximize flow access (e.g. trees), (ii) features that impede
      flow (e.g. impermeable walls, insulation) and (iii) static organs that support
      flow structures. The proportionality between body heat loss and body size raised
      to the power 3/4 is deduced from the discovery that the counterflow of two trees
      is the optimal configuration for achieving (i) and (ii) simultaneously: maximum
      fluid-flow access and minimum heat leak. Other allometric examples deduced from
      the constructal law are the flying speeds of insects, birds and aeroplanes, the
      porosity and hair strand diameter of the fur coats of animals, and the existence
      of optimal organ sizes. Body size and configuration are intrinsic parts of the
      deduced configuration. They are results, not assumptions. The constructal law
      extends physics (thermodynamics) to cover the configuration, performance, global
      size and global internal flow volume of flow systems. The time evolution of such
      configurations can be described as survival by increasing performance,
      compactness and territory.

PMID- 15855400
TI  - Modeling of vascular networks.
AB  - Vascular networks refer here mainly to the microscale capillary networks of the
      vascular system of mammals, although they may also be considered to include the
      small arteries that feed the capillaries and the small veins that drain them. The
      modeling of these networks for resting mammals is reviewed within the context of
      describing related scaling laws for mammals of vastly different size. Basic
      processes are considered and alternative approaches mentioned. All lead to the
      same scaling laws for the radius, length and number of the vessels. The
      applicability of the relations is illustrated using existing measurements.
      Discussion is also included on the effect of strenuous exercise on the scaling
      law for number of capillary vessels and matters related to it.

PMID- 15855401
TI  - Circulatory variables and the flight performance of birds.
AB  - When considering the 'burst' flight performance of birds, such as during take
      off, one of the most important structural variables is the ratio of the mass of
      the flight muscle myofibrils with respect to body mass. However, when considering
      'prolonged' flight performance the variable of interest should be the body mass
      ratio of the mass of the flight muscle myofibrils that can be perfused
      sustainably with metabolites via the blood supply. The latter variable should be
      related to blood flow (ml min(-1)), which in turn has been shown to be a function
      of heart muscle mass, the value of which is more easily obtainable for different
      species than that for the mass of perfused muscle. The limited empirical evidence
      available suggests that for birds and mammals the rate of maximum oxygen
      consumption scales with heart mass (Mh) as Mh 0.88 and that for birds Mh scales
      with body mass (Mb) as Mb 0.92, leading to the conclusion that the rate of
      maximum oxygen consumption in birds scales with an exponent of around Mb 0.82. A
      similar exponent would be expected for the rate of maximum oxygen consumption
      with respect to the flight muscle mass of birds. This suggests that the
      sustainable power output from the flight muscles may ultimately be limiting the
      flight performance of very large flying animals, but as a result of circulatory
      constraints rather than biomechanical considerations of the flight muscles per
      se. Under the particular circumstances of sustainable flight performance,
      calculations of rates of metabolic energy consumed by the flight muscles can be
      compared directly with the estimates of biomechanical power output required, as
      calculated using various aerodynamic models. The difference between these
      calculated values for rates of energy input and output from the muscles is
      equivalent to the 'apparent' mechanochemical conversion efficiency. The results
      of one such analysis, of the maximum sustainable flight performance of migratory
      birds, leads to the conclusion that the efficiency of the flight muscles appears
      to scale as Mb 0.14. However, much of this apparent scaling may be an artefact of
      the application and assumptions of the models. The resolution of this issue is
      only likely to come from studying bird species at either extreme of the size
      range.

PMID- 15855402
TI  - Control of metabolic rate is a hidden variable in the allometric scaling of
      homeotherms.
AB  - The allometric scaling exponent of the relationship between standard metabolic
      rate (SMR) and body mass for homeotherms has a long history and has been subject
      to much debate. Provided the external and internal conditions required to measure
      SMR are met, it is tacitly assumed that the metabolic rate (B) converges to SMR.
      If SMR does indeed represent a local minimum, then short-term regulatory control
      mechanisms should not operate to sustain it. This is a hidden assumption in many
      published articles aiming to explain the scaling exponent in terms of physical
      and morphological constraints. This paper discusses the findings of a minimalist
      body temperature (Tb) control model in which short-term controlling operations,
      related to the difference between Tb and the set-point temperatures by specific
      gains and time delays in the control loops, are described by a system of
      differential equations of Tb, B and thermal conductance. We found that because
      the gains in the control loops tend to increase as body size decreases (i.e.
      changes in B and thermal conductance are speeded-up in small homeotherms), the
      equilibrium point of the system potentially changes from asymptotically stable to
      a centre, transforming B and Tb in oscillating variables. Under these specific
      circumstances the very concept of SMR no longer makes sense. A series of
      empirical reports of metabolic rate in very small homeotherms supports this
      theoretical prediction, because in these animals B seems not to converge to a SMR
      value. We conclude that the unrestricted use of allometric equations to relate
      metabolic rate to body size might be misleading because metabolic control itself
      experiences size effects that are overlooked in ordinary allometric analysis.

PMID- 15855403
TI  - Body size, energy metabolism and lifespan.
AB  - Bigger animals live longer. The scaling exponent for the relationship between
      lifespan and body mass is between 0.15 and 0.3. Bigger animals also expend more
      energy, and the scaling exponent for the relationship of resting metabolic rate
      (RMR) to body mass lies somewhere between 0.66 and 0.8. Mass-specific RMR
      therefore scales with a corresponding exponent between -0.2 and -0.33. Because
      the exponents for mass-specific RMR are close to the exponents for lifespan, but
      have opposite signs, their product (the mass-specific expenditure of energy per
      lifespan) is independent of body mass (exponent between -0.08 and 0.08). This
      means that across species a gram of tissue on average expends about the same
      amount of energy before it dies regardless of whether that tissue is located in a
      shrew, a cow, an elephant or a whale. This fact led to the notion that ageing and
      lifespan are processes regulated by energy metabolism rates and that elevating
      metabolism will be associated with premature mortality--the rate of living
      theory. The free-radical theory of ageing provides a potential mechanism that
      links metabolism to ageing phenomena, since oxygen free radicals are formed as a
      by-product of oxidative phosphorylation. Despite this potential synergy in these
      theoretical approaches, the free-radical theory has grown in stature while the
      rate of living theory has fallen into disrepute. This is primarily because
      comparisons made across classes (for example, between birds and mammals) do not
      conform to the expectations, and even within classes there is substantial
      interspecific variability in the mass-specific expenditure of energy per
      lifespan. Using interspecific data to test the rate of living hypothesis is,
      however, confused by several major problems. For example, appeals that the
      resultant lifetime expenditure of energy per gram of tissue is 'too variable'
      depend on the biological significance rather than the statistical significance of
      the variation observed. Moreover, maximum lifespan is not a good marker of ageing
      and RMR is not a good measure of total energy metabolism. Analysis of residual
      lifespan against residual RMR reveals no significant relationship. However, this
      is still based on RMR. A novel comparison using daily energy expenditure (DEE),
      rather than BMR, suggests that lifetime expenditure of energy per gram of tissue
      is NOT independent of body mass, and that tissue in smaller animals expends more
      energy before expiring than tissue in larger animals. Some of the residual
      variation in this relationship in mammals is explained by ambient temperature. In
      addition there is a significant negative relationship between residual lifespan
      and residual daily energy expenditure in mammals. A potentially much better model
      to explore the links of body size, metabolism and ageing is to examine the
      intraspecific links. These studies have generated some data that support the
      original rate of living theory and other data that conflict. In particular
      several studies have shown that manipulating animals to expend more or less
      energy generate the expected effects on lifespan (particularly when the subjects
      are ectotherms). However, smaller individuals with higher rates of metabolism
      live longer than their slower, larger conspecifics. An addition to these confused
      observations has been the recent suggestion that under some circumstances we
      might expect mitochondria to produce fewer free radicals when metabolism is
      higher--particularly when they are uncoupled. These new ideas concerning the
      manner in which mitochondria generate free radicals as a function of metabolism
      shed some light on the complexity of observations linking body size, metabolism
      and lifespan.

PMID- 15855404
TI  - Problems of allometric scaling analysis: examples from mammalian reproductive
      biology.
AB  - Biological scaling analyses employing the widely used bivariate allometric model
      are beset by at least four interacting problems: (1) choice of an appropriate
      best-fit line with due attention to the influence of outliers; (2) objective
      recognition of divergent subsets in the data (allometric grades); (3) potential
      restrictions on statistical independence resulting from phylogenetic inertia; and
      (4) the need for extreme caution in inferring causation from correlation. A new
      non-parametric line-fitting technique has been developed that eliminates
      requirements for normality of distribution, greatly reduces the influence of
      outliers and permits objective recognition of grade shifts in substantial
      datasets. This technique is applied in scaling analyses of mammalian gestation
      periods and of neonatal body mass in primates. These analyses feed into a re
      examination, conducted with partial correlation analysis, of the maternal energy
      hypothesis relating to mammalian brain evolution, which suggests links between
      body size and brain size in neonates and adults, gestation period and basal
      metabolic rate. Much has been made of the potential problem of phylogenetic
      inertia as a confounding factor in scaling analyses. However, this problem may be
      less severe than suspected earlier because nested analyses of variance conducted
      on residual variation (rather than on raw values) reveals that there is
      considerable variance at low taxonomic levels. In fact, limited divergence in
      body size between closely related species is one of the prime examples of
      phylogenetic inertia. One common approach to eliminating perceived problems of
      phylogenetic inertia in allometric analyses has been calculation of 'independent
      contrast values'. It is demonstrated that the reasoning behind this approach is
      flawed in several ways. Calculation of contrast values for closely related
      species of similar body size is, in fact, highly questionable, particularly when
      there are major deviations from the best-fit line for the scaling relationship
      under scrutiny.

PMID- 15855405
TI  - Scaling and power-laws in ecological systems.
AB  - Scaling relationships (where body size features as the independent variable) and
      power-law distributions are commonly reported in ecological systems. In this
      review we analyze scaling relationships related to energy acquisition and
      transformation and power-laws related to fluctuations in numbers. Our aim is to
      show how individual level attributes can help to explain and predict patterns at
      the level of populations that can propagate at upper levels of organization. We
      review similar relationships also appearing in the analysis of aquatic ecosystems
      (i.e. the biomass spectra) in the context of ecological invariant relationships
      (i.e. independent of size) such as the 'energetic equivalence rule' and the
      'linear biomass hypothesis'. We also discuss some power-law distributions
      emerging in the analysis of numbers and fluctuations in ecological attributes as
      they point to regularities that are yet to be integrated with traditional scaling
      relationships and which we foresee as an exciting area of future research.

PMID- 15855406
TI  - A GPCR that is not "DRY".
AB  - The conserved "DRY" motif (Asp-Arg-Tyr) at the cytosolic surface of rhodopsin
      like G protein-coupled receptors has been the subject of much work attempting to
      understand the mechanisms of receptor activation and interaction with G proteins.
      Both the acidic (Asp) and basic (Arg) residues of this motif are important for
      isomerization of receptors between inactive and activated conformations. In this
      issue of Molecular Pharmacology, Rosenkilde et al. (pp. 11-19) show that a novel
      wild-type receptor, ORF74-EHV2, which lacks the Arg residue, is fully functional,
      showing both constitutive and ligand-induced activation of G protein signaling.
      Reintroducing the DRY motif by mutagenesis decreased constitutive activity while
      retaining ligand-inducible function. This work shows that the conserved Arg side
      chain is not required for receptor function, but it is important for stabilizing
      receptors in the inactive conformation.

PMID- 15855407
TI  - Differential regulation of phosphorylation of the cAMP response element-binding
      protein after activation of EP2 and EP4 prostanoid receptors by prostaglandin E2.
AB  - The EP2 and EP4 prostanoid receptors are G-protein-coupled receptors whose
      activation by their endogenous ligand, prostaglandin (PG) E2, stimulates the
      formation of intracellular cAMP. We have previously reported that the stimulation
      of cAMP formation in EP4-expressing cells is significantly less than in EP2
      expressing cells, despite nearly identical levels of receptor expression (J Biol
      Chem 277:2614-2619, 2002). In addition, a component of EP4 receptor signaling,
      but not of EP2 receptor signaling, was found to involve the activation of
      phosphatidylinositol 3-kinase (PI3K). In this study, we report that PGE2
      stimulation of cells expressing either the EP2 or EP4 receptor results in the
      phosphorylation of the cAMP response element binding protein (CREB) at serine
      133. Pretreatment of cells with N-[2-(4-bromocinnamylamino)ethyl]-5-isoquinoline
      (H-89), an inhibitor of protein kinase A (PKA), attenuated the PGE2-mediated
      phosphorylation of CREB in EP2-expressing cells, but not in EP4-expressing cells.
      Pretreatment of cells with wortmannin, an inhibitor of PI3K, had no effects on
      the PGE2-mediated phosphorylation of CREB in either EP2- or EP4-expressing cells,
      although it significantly increased the PGE2-mediated activation of PKA in EP4
      expressing cells. However, combined pretreatment with H-89 and wortmannin blocked
      PGE2-mediated phosphorylation in EP2-expressing cells as well as in EP2
      expressing cells. PGE2-mediated intracellular cAMP formation was not affected by
      pretreatment with wortmannin, or combined treatment with wortmannin and H-89, in
      either the EP2- or EP4-expressing cells. These findings suggest that PGE2
      stimulation of EP4 receptors, but not EP2 receptors, results in the activation of
      a PI3K signaling pathway that inhibits the activity of PKA and that the PGE2
      mediated phosphorylation of CREB by these receptors occurs through different
      signaling pathways

PMID- 15855409
TI  - Bayesian network analysis of signaling networks: a primer.
AB  - High-throughput proteomic data can be used to reveal the connectivity of
      signaling networks and the influences between signaling molecules. We present a
      primer on the use of Bayesian networks for this task. Bayesian networks have been
      successfully used to derive causal influences among biological signaling
      molecules (for example, in the analysis of intracellular multicolor flow
      cytometry). We discuss ways to automatically derive a Bayesian network model from
      proteomic data and to interpret the resulting model.

PMID- 15855408
TI  - Receptor signaling and endocytosis are differentially regulated by somatostatin
      analogs.
AB  - Upon hormone stimulation, the sst2 somatostatin receptor couples to adenylyl
      cyclase through G(i/o) proteins and undergoes rapid endocytosis via clathrin
      coated pits. In this study, we determined the relationship between the ability of
      ligands to induce sst2 receptor internalization and inhibit adenylyl cyclase.
      Immunocytochemical studies demonstrated that peptide agonists [such as
      somatostatin-14, cortistatin-17, octreotide, vapreotide, KE108 (Tyr0-cyclo[d
      diaminobutyric acid-Arg-Phe-Phe-d-Trp-Lys-Thr-Phe]), and SOM230
      (cyclo[diaminoethylcarbamoyl-hydroxyproline-phenylglycine-d-Trp-Lys-(4-O-benzyl)
      l-Tyr-Phe])] and nonpeptide agonists (such as L-779,976), stimulated the rapid
      endocytosis of sst2 receptors in human embryonic kidney 293 and CHO-K1 cells. In
      contrast, two antagonists did not induce receptor endocytosis by themselves and
      completely blocked agonist stimulation. Using a quantitative enzyme-linked
      immunosorbent assay to measure sst2 receptor sequestration, we found that peptide
      agonists varied by more than 100-fold in their potencies but exhibited the same
      efficacy as somatostatin14. In contrast, L-779,976 did not induce maximal
      receptor internalization. It is interesting that although betaarrestin-2 was
      recruited to cell surface sst2 receptors after stimulation with either
      somatostatin14 or L-779,976, the betaarrestin-receptor complex dissociated
      earlier in the endocytic pathway with the nonpeptide ligand. Although all
      agonists, including L-779,976, produced the same maximal inhibition of cyclic
      AMP, the potency ratio for inhibition of cyclic AMP and stimulation of receptor
      endocytosis varied by 15-fold. In general, native peptides showed similar
      potencies for cyclic AMP inhibition and receptor endocytosis, whereas short
      therapeutic analogs were substantially more potent at inhibiting cyclic AMP
      synthesis. These results demonstrate that the activity of somatostatin analogs to
      regulate receptor endocytosis and signaling are not tightly linked and provide
      compelling evidence for the induction of agonist specific states of the sst2
      receptor.

PMID- 15855410
TI  - Inducible covalent posttranslational modification of histone H3.
AB  - The physiological state of a eukaryotic cell is determined by endogenous and
      exogenous signals, and often the endpoint of the pathways that transmit these
      signals is DNA. DNA is organized into chromatin, a nucleoprotein complex, which
      not only facilitates the packaging of DNA within the nucleus but also serves as
      an important factor in the regulation of gene function. The nucleosome is the
      basic unit of chromatin and generally consists of approximately two turns of DNA
      wrapped around an octamer of core histone proteins. Each histone also contains an
      accessible N-terminal tail that extends outside the chromatin complex and is
      subject to posttranslational modifications that are crucial in the regulation of
      gene expression. Two distinct categories of histone posttranslational
      modification have been observed: (i) inducible or stimulation-dependent and (ii)
      mitosis-dependent. Stimulation by mitogens or stress leads to rapid transient
      posttranslational modifications of histones, in particular histone H3, which are
      mechanistically and temporarily distinct from modifications associated with
      mitosis. This Review focuses mainly on the inducible phosphorylation of histone
      H3 brought about by different stimuli, such as epidermal growth factor, 12-O
      tetradecanoylphorbol-13-acetate, arsenite, or ultraviolet radiation. We examine
      the most recent, and at times controversial, research data concerning the
      identity of the histone H3 kinases responsible for this phosphorylation. In
      addition, the interdependence of phosphorylation and acetylation will be
      discussed in light of data showing patterns of inducible modification at specific
      genes.

PMID- 15855411
TI  - Ubiquitin chains in the ladder of MAPK signaling.
AB  - With a better understanding of the cellular stress response, it has become
      evident that catalytic modules consisting of kinases that mediate the activation
      of downstream effector components are subject to multiple layers of regulation.
      Such regulatory mechanisms are not limited to those involving scaffold proteins
      or protein phosphatases, and they appear to include a growing number of
      modifications by ubiquitin and ubiquitin-like proteins. The role of ubiquitin in
      the regulation of mitogen-activated protein kinase (MAPK) emerges as a paradigm
      for understanding the role of ubiquitination in regulating other signal
      transduction pathways. Ubiquitination influences signal diversification and
      limits the duration of the signal through its role in the assembly of protein
      kinase complexes, subcellular localization, and the actual degradation of the
      kinase or its substrate. This review summarizes our current understanding of the
      roles of ubiquitin in regulating MAPK signaling.

PMID- 15855412
TI  - Teaching resources. G-protein effectors.
AB  - This Teaching Resource provides lecture notes and slides for a class covering two
      aspects of G protein-mediated signaling and is part of the course "Cell Signaling
      Systems: A Course for Graduate Students." The lecture begins with a discussion of
      the regulation of receptor-G protein coupling and then proceeds to describe the
      specificity of the response achieved through regulation of specific isoforms of
      effectors.

PMID- 15855413
TI  - Still Life With Jar, Cup, and Apples.

PMID- 15855414
TI  - Mysteries of the X chromosome revealed: "silent" X not always mute.

PMID- 15855415
TI  - Will lung cancer targeting hit its mark?

PMID- 15855416
TI  - Nanoscale biosensors show promise.

PMID- 15855423
TI  - Obesity and the risk of new-onset atrial fibrillation.

PMID- 15855424
TI  - Obesity and the risk of new-onset atrial fibrillation.

PMID- 15855425
TI  - Obesity and the risk of new-onset atrial fibrillation.

PMID- 15855426
TI  - Arthritis medications and cardiovascular events.

PMID- 15855427
TI  - Arthritis medications and cardiovascular events.

PMID- 15855428
TI  - Arthritis medications and cardiovascular events.

PMID- 15855429
TI  - Tramadol abuse and dependence among physicians.

PMID- 15855431
TI  - Lower cancer incidence in Amsterdam-I criteria families without mismatch repair
      deficiency: familial colorectal cancer type X.
AB  - CONTEXT: Approximately 60% of families that meet the Amsterdam-I criteria (AC-I)
      for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary
      abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I
      families with MMR gene mutations is reported to be very high, but cancer
      incidence for individuals in AC-I families with no evidence of an MMR defect is
      unknown. OBJECTIVE: To determine if cancer risks in AC-I families with no
      apparent deficiency in DNA MMR are different from cancer risks in AC-I families
      with DNA MMR abnormalities. DESIGN, SETTING, AND PARTICIPANTS: Identification
      (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based
      sources in North America and Germany, with families grouped into those with
      (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422
      relatives were included in the analyses. MAIN OUTCOME MEASURES: Cancer incidence
      in groups A and B (excluding the 3 affected members used to define each pedigree
      as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs)
      using Surveillance, Epidemiology, and End Results data. RESULTS: Group A families
      from both population- and clinic-based series showed increased incidence of the
      HNPCC-related cancers. Group B families showed increased incidence only for
      colorectal cancer (SIR, 2.3; 95% confidence interval, 1.7-3.0) and to a lesser
      extent than group A (SIR, 6.1; 95% confidence interval, 5.2-7.2) (P<.001).
      CONCLUSIONS: Families who fulfill AC-I criteria but who have no evidence of a DNA
      MMR defect do not share the same cancer incidence as families with HNPCC-Lynch
      syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower
      incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome,
      and incidence may not be increased for other cancers. These families should not
      be described or counseled as having HNPCC-Lynch syndrome. To facilitate
      distinguishing these entities, the designation of "familial colorectal cancer
      type X" is suggested to describe this type of familial aggregation of colorectal
      cancer.

PMID- 15855432
TI  - Accuracy of revised Bethesda guidelines, microsatellite instability, and
      immunohistochemistry for the identification of patients with hereditary
      nonpolyposis colorectal cancer.
AB  - CONTEXT: The selection of individuals for hereditary nonpolyposis colorectal
      cancer (HNPCC) genetic testing is challenging. Recently, the National Cancer
      Institute outlined a new set of recommendations, the revised Bethesda guidelines,
      for the identification of individuals with HNPCC who should be tested for
      microsatellite instability. OBJECTIVE: To establish the most effective and
      efficient strategy for the detection of MSH2/MLH1 gene carriers. DESIGN, SETTING,
      AND PATIENTS: A prospective, multicenter, nationwide study (the EPICOLON study)
      in 20 hospitals in the general community in Spain of 1222 patients with newly
      diagnosed colorectal cancer between November 1, 2000, and October 31, 2001.
      INTERVENTIONS: Microsatellite instability testing and MSH2/MLH1 immunostaining in
      all patients regardless of age, personal or family history, and tumor
      characteristics. Patients whose tumors exhibited microsatellite instability
      and/or lack of protein expression underwent MSH2/MLH1 germline testing. MAIN
      OUTCOME MEASURES: Effectiveness and efficiency of both microsatellite instability
      testing and immunostaining, either directly or previous selection of patients
      according to the revised Bethesda guidelines, were evaluated with respect to the
      presence of MSH2/MLH1 germline mutations. RESULTS: Two hundred eighty-seven
      patients (23.5%) fulfilled the revised Bethesda guidelines. Ninety-one patients
      (7.4%) had a mismatch repair deficiency, with tumors exhibiting either
      microsatellite instability (n = 83) or loss of protein expression (n = 81).
      Germline testing identified 11 mutations (0.9%) in either MSH2 (7 cases) or MLH1
      (4 cases) genes. Strategies based on either microsatellite instability testing or
      immunostaining previous selection of patients according to the revised Bethesda
      guidelines were the most effective (sensitivity, 81.8% and 81.8%; specificity,
      98.0% and 98.2%; positive predictive value, 27.3% and 29.0%, respectively) to
      identify MSH2/MLH1 gene carriers. Logistic regression analysis confirmed the
      revised Bethesda guidelines as the most discriminating set of clinical parameters
      (odds ratio, 33.3; 95% confidence interval, 4.3-250; P = .001). CONCLUSION: The
      revised Bethesda guidelines constitute a useful approach to identify patients at
      risk for HNPCC. In patients fulfilling these criteria, both microsatellite
      instability testing and immunostaining are equivalent and highly effective
      strategies to further select those patients who should be tested for MSH2/MLH1
      germline mutations.

PMID- 15855433
TI  - Influence of patients' requests for direct-to-consumer advertised
      antidepressants: a randomized controlled trial.
AB  - CONTEXT: Direct-to-consumer (DTC) advertising of prescription drugs in the United
      States is both ubiquitous and controversial. Critics charge that it leads to
      overprescribing, while proponents counter that it helps avert underuse of
      effective treatments, especially for conditions that are poorly recognized or
      stigmatized. OBJECTIVE: To ascertain the effects of patients' DTC-related
      requests on physicians' initial treatment decisions in patients with depressive
      symptoms. DESIGN: Randomized trial using standardized patients (SPs). Six SP
      roles were created by crossing 2 conditions (major depression or adjustment
      disorder with depressed mood) with 3 request types (brand-specific, general, or
      none). SETTING: Offices of primary care physicians in Sacramento, Calif; San
      Francisco, Calif; and Rochester, NY, between May 2003 and May 2004. PARTICIPANTS:
      One hundred fifty-two family physicians and general internists recruited from
      solo and group practices and health maintenance organizations; cooperation rates
      ranged from 53% to 61%. INTERVENTIONS: The SPs were randomly assigned to make 298
      unannounced visits, with assignments constrained so physicians saw 1 SP with
      major depression and 1 with adjustment disorder. The SPs made a brand-specific
      drug request, a general drug request, or no request (control condition) in
      approximately one third of visits. MAIN OUTCOME MEASURES: Data on prescribing,
      mental health referral, and primary care follow-up obtained from SP written
      reports, visit audiorecordings, chart review, and analysis of written
      prescriptions and drug samples. The effects of request type on prescribing were
      evaluated using contingency tables and confirmed in generalized linear mixed
      models that accounted for clustering and adjusted for site, physician, and visit
      characteristics. RESULTS: Standardized patient role fidelity was excellent, and
      the suspicion rate that physicians had seen an SP was 13%. In major depression,
      rates of antidepressant prescribing were 53%, 76%, and 31% for SPs making brand
      specific, general, and no requests, respectively (P<.001). In adjustment
      disorder, antidepressant prescribing rates were 55%, 39%, and 10%, respectively
      (P<.001). The results were confirmed in multivariate models. Minimally acceptable
      initial care (any combination of an antidepressant, mental health referral, or
      follow-up within 2 weeks) was offered to 98% of SPs in the major depression role
      making a general request, 90% of those making a brand-specific request, and 56%
      of those making no request (P<.001). CONCLUSIONS: Patients' requests have a
      profound effect on physician prescribing in major depression and adjustment
      disorder. Direct-to-consumer advertising may have competing effects on quality,
      potentially both averting underuse and promoting overuse.

PMID- 15855435
TI  - Clinical validity of a negative computed tomography scan in patients with
      suspected pulmonary embolism: a systematic review.
AB  - CONTEXT: The clinical validity of using computed tomography (CT) to diagnose
      peripheral pulmonary embolism is uncertain. Insufficient sensitivity for
      peripheral pulmonary embolism is considered the principal limitation of CT.
      OBJECTIVE: To review studies that used a CT-based approach to rule out a
      diagnosis of pulmonary embolism. DATA SOURCES: The medical literature databases
      of PubMed, MEDLINE, EMBASE, CRISP, metaRegister of Controlled Trials, and
      Cochrane were searched for articles published in the English language from
      January 1990 to May 2004. STUDY SELECTION: We included studies that used contrast
      enhanced chest CT to rule out the diagnosis of acute pulmonary embolism, had a
      minimum follow-up of 3 months, and had study populations of more than 30
      patients. DATA EXTRACTION: Two reviewers independently abstracted patient
      demographics, frequency of venous thromboembolic events (VTEs), CT modality
      (single-slice CT, multidetector-row CT, or electron-beam CT), false-negative
      results, and deaths attributable to pulmonary embolism. To calculate the overall
      negative likelihood ratio (NLR) of a VTE after a negative or inconclusive chest
      CT scan for pulmonary embolism, we included VTEs that were objectively confirmed
      by an additional imaging test despite a negative or inconclusive CT scan and
      objectively confirmed VTEs that occurred during clinical follow-up of at least 3
      months. DATA SYNTHESIS: Fifteen studies met the inclusion criteria and contained
      a total of 3500 patients who were evaluated from October 1994 through April 2002.
      The overall NLR of a VTE after a negative chest CT scan for pulmonary embolism
      was 0.07 (95% confidence interval [CI], 0.05-0.11); and the negative predictive
      value (NPV) was 99.1% (95% CI, 98.7%-99.5%). The NLR of a VTE after a negative
      single-slice spiral CT scan for pulmonary embolism was 0.08 (95% CI, 0.05-0.13);
      and after a negative multidetector-row CT scan, 0.15 (95% CI, 0.05-0.43). There
      was no difference in risk of VTEs based on CT modality used (relative risk, 1.66;
      95% CI, 0.47-5.94; P = .50). The overall NLR of mortality attributable to
      pulmonary embolism was 0.01 (95% CI, 0.01-0.02) and the overall NPV was 99.4%
      (95% CI, 98.7%-99.9%). CONCLUSION: The clinical validity of using a CT scan to
      rule out pulmonary embolism is similar to that reported for conventional
      pulmonary angiography.

PMID- 15855434
TI  - Neuroprotective and anti-human immunodeficiency virus activity of minocycline.
AB  - CONTEXT: The prevalence of human immunodeficiency virus (HIV) central nervous
      system (CNS) disease has not decreased despite highly active antiretroviral
      therapy. Current antiretroviral drugs are expensive, have significant adverse
      effects including neurotoxicity, and few cross the blood-brain barrier.
      OBJECTIVE: To examine the ability of minocycline, an antibiotic with potent anti
      inflammatory and neuroprotective properties, to protect against encephalitis and
      neurodegeneration using a rapid, high viral load simian immunodeficiency virus
      (SIV) model of HIV-associated CNS disease that constitutes a rigorous in vivo
      test for potential therapeutics. DESIGN AND SUBJECTS: Five SIV-infected pigtailed
      macaques were treated with 4 mg/kg per day of minocycline beginning at early
      asymptomatic infection (21 days after inoculation). Another 6 macaques were
      inoculated with SIV but remained untreated. Blood and cerebrospinal fluid (CSF)
      samples were taken on days 7, 10, 14, 21, 28, 35, 43, 56, 70, 77, and 84, and all
      macaques were humanely killed at 84 days after inoculation, a time that
      corresponds to late-stage infection in HIV-infected individuals. MAIN OUTCOME
      MEASURES: Blood and CSF samples were tested for viral load by real-time reverse
      transcription-polymerase chain reaction and levels of monocyte chemoattractant
      protein 1 were quantitated by enzyme-linked immunosorbent assay. The presence and
      severity of encephalitis was determined by microscopic examination of tissues.
      Central nervous system inflammation was further assessed by measuring
      infiltration and activation of macrophages, activation of p38 mitogen-activated
      protein kinase and expression of amyloid precursor protein by quantitative
      immunohistochemistry. RESULTS: Minocycline-treated macaques had less severe
      encephalitis (P = .02), reduced CNS expression of neuroinflammatory markers
      (major histocompatibility complex class II, P = .03; macrophage marker CD68 , P =
      .07; T-cell intracytoplasmic antigen 1, P = .03; CSF monocyte chemoattractant
      protein 1, P = .001), reduced activation of p38 mitogen-activated protein kinase
      (P<.001), less axonal degeneration (beta-amyloid precursor protein, P = .03), and
      lower CNS virus replication (viral RNA, P = .04; viral antigen, P = .04). In in
      vitro analysis, minocycline suppression of HIV and SIV replication in cultured
      primary macrophages did not correlate with suppression of activation of p38
      mitogen-activated protein kinase pathways, whereas suppression in primary
      lymphocytes correlated with suppression of p38 activation. CONCLUSIONS: In this
      experimental SIV model of HIV CNS disease, minocycline reduced the severity of
      encephalitis, suppressed viral load in the brain, and decreased the expression of
      CNS inflammatory markers. In vitro, minocycline inhibited SIV and HIV
      replication. These findings suggest that minocycline, a safe, inexpensive, and
      readily available antibiotic should be investigated as an anti-HIV therapeutic.

PMID- 15855436
TI  - An 80-year-old woman with vaginal prolapse.

PMID- 15855437
TI  - A 50-year-old man with hepatitis C and cirrhosis needing liver transplantation,
      18 months later.

PMID- 15855438
TI  - Progress in genetic testing, classification, and identification of Lynch
      syndrome.

PMID- 15855439
TI  - Direct-to-consumer advertising: a haphazard approach to health promotion.

PMID- 15855440
TI  - JAMA patient page. Uterine prolapse.

PMID- 15855446
TI  - Community-oriented primary care and primary health care.

PMID- 15855447
TI  - Understanding and addressing the health care needs of American Indians and Alaska
      Natives.

PMID- 15855448
TI  - The Baltimore Youth Ammunition Initiative: a model application of local public
      health authority in preventing gun violence.
AB  - In 2002, the Baltimore City Health Department, in collaboration with the
      Baltimore Police Department and the Johns Hopkins Center for Gun Policy and
      Research, launched the Youth Ammunition Initiative. The initiative addressed
      Baltimore's problem of youth gun violence by targeting illegal firearm ammunition
      sales to the city's young people. The initiative included undercover "sting"
      investigations of local businesses and issuance of health department violation
      and abatement notices. Intermediate results included the passage of 2 Baltimore
      city council ordinances regulating ammunition sales and reducing the number of
      outlets eligible to sell ammunition. Although it is too early to assess effects
      on violent crime, the intervention could theoretically reduce youth violence by
      interrupting one source of ammunition to youths. More important, the initiative
      can serve as a policy model for health commissioners seeking to become more
      active in gun violence prevention efforts.

PMID- 15855449
TI  - Reforming American Indian/Alaska Native health care financing: the role of
      Medicaid.
AB  - Chronic underfunding of American Indian and Alaska Native (AIAN) health care by
      the federal government has weakened the capacity of the Indian Health Service,
      tribal governments, and the urban Indian health delivery system to meet the
      health care needs of the AIAN population. I describe the current role of Medicaid
      in financing health care services for American Indians/Alaska Natives and offer 3
      suggestions for reforming Medicaid financing of AIAN health care: (1) apply a
      100% federal matching rate to the cost of Medicaid services furnished by urban
      Indian health programs; (2) apply a 100% federal matching rate to the cost of
      Medicaid services furnished by referral to AIAN patients of hospitals or clinics
      operated by the Indian Health Service, tribes, tribal organizations, or urban
      Indian health programs; and (3) exempt AIAN Medicaid beneficiaries who receive
      services from such hospitals or clinics from state reductions in Medicaid
      eligibility and benefits.

PMID- 15855450
TI  - Improving the oral health of Alaska Natives.
AB  - There is a high prevalence of oral disease in the Alaska Native population, much
      of which goes untreated, creating a large discrepancy between the level of their
      oral health and that of the general population. The causes of this discrepancy
      are multiple--a major cause being the lack of access to care, especially in
      remote Alaska Native villages. Improving the oral health status of Alaska Natives
      will require treatment of current disease and initiation of an effective program
      to prevent oral disease. Cooperation between the Alaska Native organizations,
      dental health aides, the dental profession, and the government will be important.
      A strategy that combines addressing the disease currently present and preventing
      the occurrence of disease in the long run is the only strategy that offers a
      sustainable solution.

PMID- 15855451
TI  - Can we capitalize on the virtues of vaccines? Insights from the polio eradication
      initiative.
AB  - Twenty-five years after the eradication of smallpox, the ongoing effort to
      eradicate poliomyelitis has grown into the largest international health
      initiative ever undertaken. By 2004, however, the polio eradication effort was
      threatened by a challenge regularly faced by public health policymakers
      everywhere-misperception about the benefits and risks of vaccines. The
      propagation of false rumors about oral poliovirus vaccine safety led to the
      reinfection of 13 previously polio-free countries and the largest polio epidemic
      in Africa in recent years. With deft management of such challenges by local,
      national, and international health authorities, poliomyelitis, a disease that
      threatened children everywhere just 2 generations ago, could soon be relegated to
      history like smallpox before it.

PMID- 15855452
TI  - Public health and the politics of school immunization requirements.
AB  - Compulsory vaccination has contributed to the enormous success of US immunization
      programs. Movements to introduce broad "philosophical/personal beliefs"
      exemptions administered without adequate public health oversight threaten this
      success. Health professionals and child welfare advocates must address these
      developments in order to maintain the effectiveness of the nation's mandatory
      school vaccination programs. We review recent events regarding mandatory
      immunization in Arkansas and discuss a proposed nonmedical exemption designed to
      allow constitutionally permissible, reasonable, health-oriented administrative
      control over exemptions. The proposal may be useful in political environments
      that preclude the use of only medical exemptions. Our observations may assist
      states whose current nonmedical exemption provisions are constitutionally suspect
      as well as states lacking legally appropriate administrative controls on
      existing, broad non-medical exemptions.

PMID- 15855453
TI  - Building healthy tribal nations in Montana and Wyoming through collaborative
      research and development.
AB  - We describe a collaborative approach to reducing health disparities affecting
      Montana and Wyoming tribal nations while promoting health-protective practices
      and interventions among these populations. Under the auspices of the Montana
      Wyoming Tribal Leaders Council, a consortium has undertaken activities to (1)
      establish the research infrastructure necessary for conducting ongoing health
      disparities research, (2) develop a target research agenda that addresses
      tribally identified priority health issues and tests the feasibility of
      interventions, (3) develop increased research skills and cultural competency
      through mentoring activities, and (4) develop effective collaborative
      relationships. All research projects are user-defined and -authorized, and
      participation is voluntary.

PMID- 15855454
TI  - Passive immunization against poliomyelitis: the Hammon gamma globulin field
      trials, 1951-1953.
AB  - Poliomyelitis has gone from being one of the worst scourges of the 20th century
      to nearing eradication in the 21st. This success is well known to be attributable
      to the Salk inactivated and Sabin attenuated poliovirus vaccines.However, before
      introduction of these vaccines, William McDowall Hammon of the University of
      Pittsburgh Graduate School of Public Health led the first major breakthrough in
      prevention of the disease by using passive immunization in one of the earliest
      double-blind, placebo-controlled clinical trials. This study provided the first
      evidence that antibodies to poliovirus could prevent the disease in humans.

PMID- 15855455
TI  - Evaluating the safety of new vaccines: summary of a workshop.
AB  - Public concerns about the safety of vaccines arise on a regular basis. In
      November 2000, a workshop titled "Evaluation of New Vaccines: How Much Safety
      Data?" was convened by US Public Health Service agencies, including the Food and
      Drug Administration, the National Institutes of Health, the Centers for Disease
      Control and Prevention, and the Health Resources and Services Administration, to
      discuss appropriate methods for evaluating the safety of new vaccines. Workshop
      presentations addressed the current standards and approaches for new vaccine
      evaluation and postlicensure surveillance, as well as public views about vaccine
      safety and alternative approaches that could be considered. The advantages and
      disadvantages of conducting large controlled trials before licensure or
      widespread use of a new vaccine were discussed. We summarize these presentations
      and discussions.

PMID- 15855456
TI  - "I have an evil child at my house": stigma and HIV/AIDS management in a South
      African community.
AB  - We examined the social roots of stigma by means of a case study of HIV/AIDS
      management among young people in a South African community (drawing from
      interviews, focus groups, and fieldworker diaries). We highlight the web of
      representations that sustain stigma, the economic and political contexts within
      which these representations are constructed, and the way in which they flourish
      in the institutional contexts of HIV/AIDS interventions. Stigma serves as an
      effective form of "social psychological policing" by punishing those who have
      breached unequal power relations of gender, generation, and ethnicity. We outline
      an agenda for participatory programs that promote critical thinking about
      stigma's social roots to stand alongside education and, where possible,
      legislation as an integral part of antistigma efforts.

PMID- 15855457
TI  - Pathways to recurrent trauma among young Black men: traumatic stress, substance
      use, and the "code of the street".
AB  - Recurrent interpersonal violence is a major cause of death and disability among
      young Black men. Quantitative studies have uncovered factors associated with
      reinjury, but little is known about how these factors work together. We
      interviewed young Black male victims to understand their experience of violence.
      Qualitative analysis of their narratives revealed how their struggle to
      reestablish safety shaped their response to injury. Aspects of the "code of the
      street" (including the need for respect) and lack of faith in the police combined
      with traumatic stress and substance use to accentuate their sense of
      vulnerability. Victims then reacted to protect themselves in ways that could
      increase their risk of reinjury. We describe a model with implications for
      reducing rates of recurrent violent injuries.

PMID- 15855458
TI  - Disparities in chronic disease risk factors and health status between American
      Indian/Alaska Native and White elders: findings from a telephone survey, 2001 and
      2002.
AB  - We compared prevalence estimates of chronic disease risk factors and health
      status between American Indian/Alaska Native (AIAN) and White elders. We used
      2001 and 2002 Behavioral Risk Factor Surveillance System data to estimate the
      prevalence of smoking, physical inactivity, obesity, diagnosed diabetes, and
      general health status. For all health behavior and status measures, American
      Indians/Alaska Natives reported greater risk than did Whites. Risk factors among
      AIAN elders need to be addressed to eliminate disparities in chronic diseases.

PMID- 15855459
TI  - Underestimation of cardiovascular disease mortality among Maine American Indians:
      the role of procedural and data errors.
AB  - We collaborated with Maine American Indian tribes to evaluate racial coding on
      death certificates and the effects of coding errors on estimation of
      cardiovascular disease (CVD) mortality. Lists of tribal decedents were matched to
      death certificates; 38.5% were misclassified (17.8% coding errors; 20.7% data
      entry errors). After errors were corrected, CVD mortality trends were similar
      between American Indians and all Maine residents. Racial misclassification
      occurred during a period when budget cuts had prompted procedural changes.

PMID- 15855460
TI  - Employer policies toward guns and the risk of homicide in the workplace.
AB  - This population-based case-control study of North Carolina workplaces evaluated
      the hypothesis that employers' policies allowing firearms in the workplace may
      increase workers' risk of homicide. Workplaces where guns were permitted were
      about 5 times as likely to experience a homicide as those where all weapons were
      prohibited (adjusted odds ratio=4.81; 95% confidence interval=1.70, 13.65). The
      association remained after adjustment for other risk factors. The findings
      suggest that policies allowing guns in the workplace might increase workers' risk
      of homicide.

PMID- 15855461
TI  - Lack of national primary care organization partnerships with community groups to
      promote health care reform.
AB  - Coalitions are necessary for successful political change. Few national primary
      care provider organizations partner with community, consumer, or labor
      organizations, and very few do so to promote policy on access to health care.
      Many of these provider organizations do work on health care access policy issues
      and do work in partnership with a variety of organizations, suggesting that
      community-provider partnerships may be a promising but overlooked strategy for
      promoting health care reform.

PMID- 15855462
TI  - Ethnic inequalities in cancer survival in New Zealand: linkage study.
AB  - We explored the contribution of stage at diagnosis to ethnic disparities in
      cancer survival in New Zealand. We linked 115811 adult patients with invasive
      cancer registered on the cancer registry (1994 to 2002) to mortality data. Age
      standardized, 5-year relative survival rates were lowest for Maori, intermediate
      for Pacific people (otherwise known as Pacific Islanders), and highest for non
      Maori/non-Pacific people for many cancers. Stage at diagnosis accounted for only
      part of these differences. Possible factors responsible for ethnic inequalities
      might include access to specialized cancer services and the quality of care
      received.

PMID- 15855463
TI  - Measuring the health status gap for American Indians/Alaska Natives: getting
      closer to the truth.
AB  - OBJECTIVES: We compared the historical method of calculating cancer incidence
      rates with 2 new methods to determine which approach optimally estimates the
      burden of cancer among the Northwest American Indian/Alaska Native (AIAN)
      population. METHODS: The first method replicates the traditional way of
      calculating race-specific rates, and the 2 new methods use probabilistic record
      linkages to ascertain cancer cases. We indirectly adjusted all rates to the
      standard 2000 US population. RESULTS: Whereas the historical cancer incidence
      rates for all races are more than double those for the AIAN population, this
      apparent gap is considerably narrower when the all-race rates are compared with
      AIAN-specific rates calculated with probabilistic linkage methods. Similarly,
      there is no meaningful difference in incidence rates for selected site- and
      gender-specific cancers between the AIAN population and all races combined, and,
      in fact, some of these rates may be higher among the AIAN population.
      CONCLUSIONS: Our results suggest that the burden of cancer among the AIAN
      population is considerably higher than was previously understood. We recommend
      that a standardized approach based on probabilistic linkage methods be adopted
      and that adequate financial and technical support be made available for
      conducting routine linkage studies throughout Indian communities.

PMID- 15855464
TI  - Disparities in indigenous health: a cross-country comparison between New Zealand
      and the United States.
AB  - OBJECTIVES: We compared the health statuses of the indigenous populations of New
      Zealand and the United States with those of the numerically dominant populations
      of these countries. METHODS: Health indicators compared included health outcome
      measures, preventive care measures, modifiable risk factor prevalence, and
      treatment measures. RESULTS: In the case of nearly every health status indicator
      assessed, disparities (both absolute and relative) were more pronounced for
      Maoris than for American Indians/Alaska Natives. Both indigenous populations
      suffered from disparities across a range of health indicators. However, no
      disparities were observed for American Indians/Alaska Natives in regard to
      immunization coverage. CONCLUSIONS: Ethnic health disparities appear to be more
      pronounced in New Zealand than in the United States. These disparities are not
      necessarily intractable. Although differences in national health sector responses
      exist, New Zealand may be well placed in the future to evaluate the effectiveness
      of new strategies to reduce these disparities given the extent and quality of
      Maori-specific health information available.

PMID- 15855465
TI  - Social epidemiology of trauma among 2 American Indian reservation populations.
AB  - OBJECTIVES: We examined the prevalence of trauma in 2 large American Indian
      communities in an attempt to describe demographic correlates and to compare
      findings with a representative sample of the US population. METHODS: We
      determined differences in exposure to each of 16 types of trauma among 3084
      tribal members aged 15 to 57 years through structured interviews. We compared
      prevalence rates of trauma, by gender, across the 2 tribes and with a sample of
      the US general population. We used logistic regression analyses to examine the
      relationships of demographic correlates to trauma exposure. RESULTS: Lifetime
      exposure rates to at least 1 trauma (62.4%-67.2% among male participants, 66.2%
      69.8% among female participants) fell at the upper limits of the range reported
      by other researchers. Unlike the US general population, female and male American
      Indians exhibited equivalent levels of overall trauma exposure. Members of both
      tribes more often witnessed traumatic events, experienced traumas to loved ones,
      and were victims of physical attacks than their counterparts in the overall US
      population. CONCLUSIONS: American Indians live in adverse environments that place
      them at high risk for exposure to trauma and harmful health sequelae.

PMID- 15855466
TI  - Lifetime prevalence of pathological gambling among american Indian and Hispanic
      American Veterans.
AB  - OBJECTIVES: We examined the prevalence and clinical correlates of pathological
      gambling among 1228 American Indian and Hispanic American veterans in the
      southwest and north central regions of the United States. METHODS: We surveyed a
      community sample of American Indian and Hispanic American veterans to obtain data
      on psychiatric disorder and treatment. RESULTS: American Indian veterans had a
      10% lifetime prevalence of pathological gambling. The Hispanic American lifetime
      prevalence was less than that of the American Indian veterans but higher than the
      prevalence found for Hispanic American veterans in other surveys. Comorbid
      conditions associated with pathological gambling included substance, mood, and
      antisocial personality disorders. Ready access to casino gambling may encourage,
      support, or contribute to high rates of pathological gambling in both men and
      women. CONCLUSIONS: A 70% lifetime comorbidity of psychiatric disorders suggests
      that early interventions for pathological gambling should consider common
      psychiatric conditions rather than focusing on pathological gambling alone.

PMID- 15855467
TI  - Correlates of cigarette smoking among selected Southwest and Northern plains
      tribal groups: the AI-SUPERPFP Study.
AB  - OBJECTIVES: We describe the prevalence and correlates of cigarette smoking in 2
      American Indian tribal groups. METHODS: We performed multinomial logistic
      regression on epidemiological data from a population-based, cross-sectional study
      of Southwest and Northern Plains American Indians aged 15 to 54 years. RESULTS:
      We found that 19% of Southwest men, 10% of Southwest women, 49% of Northern
      Plains men, and 51% of Northern Plains women were current smokers. Male gender
      and younger age were associated with higher odds of smoking in the Southwest
      tribe, whereas current or former marriage and having spent less time on a
      reservation were associated with higher odds of smoking in the Northern Plains
      population. Alcohol consumption was strongly associated with higher odds of
      smoking in both groups. CONCLUSIONS: Cigarette smoking is a major public health
      concern among American Indians. Because correlates and smoking patterns vary
      among different tribal groups, each group's unique characteristics should be
      considered when designing and implementing comprehensive, culturally appropriate
      interventions in American Indian communities.

PMID- 15855468
TI  - Tuberculosis among American Indians and Alaska Natives in the United States, 1993
      2002.
AB  - OBJECTIVES: I examined trends in and epidemiological and clinical characteristics
      of tuberculosis (TB) within the American Indian/Alaska Native (AIAN) population
      of the United States and compared TB trends and characteristics in that
      population with TB trends and characteristics within other racial/ethnic groups.
      METHODS: I analyzed all verified cases of TB reported to the US National
      Tuberculosis Surveillance System from January 1, 1993, to December 31, 2002.
      RESULTS: From 1993 through 2002, 196133 TB cases were reported, 2612 (1.3%) of
      which were in the AIAN population. During this period, TB case rates declined
      40.4% among AIAN peoples, the smallest decrease among any US-born racial/ethnic
      group. In 2002, 15075 TB cases (5.2 per 100000 population) were reported, 180 of
      which were in the AIAN population (8.4 per 100000 population)-almost 6 times the
      rate for non-Hispanic Whites (1.5 per 100000 population). CONCLUSIONS: TB
      continues to be a significant health problem for the AIAN population. Vigilance
      and collaboration among local, state, federal, AIAN, and tribal TB control
      programs are essential to TB elimination among the AIAN population.

PMID- 15855469
TI  - Causes of visual impairment and common eye problems in Northwest American Indians
      and Alaska Natives.
AB  - OBJECTIVES: Little information exists regarding the causes of visual impairment
      and the most common eye problems in American Indians/Alaska Natives. METHODS: We
      randomly sampled American Indians/Alaska Natives older than 40 years from 3
      tribes within the Northwest region. RESULTS: We found a higher prevalence of
      visual impairment and normal-tension glaucoma, as well as a lower prevalence of
      ocular hypertension, in American Indians/Alaska Natives compared with previous
      results in other racial/ethnic groups. CONCLUSIONS: American Indians/Alaska
      Natives have a need for vision correction. Future interventions in American
      Indians/Alaska Natives should include providing spectacles for refractive error,
      detecting glaucoma, and preventing visual impairment from age-related maculopathy
      and cataracts.

PMID- 15855470
TI  - Early alcohol initiation and subsequent sexual and alcohol risk behaviors among
      urban youths.
AB  - OBJECTIVES: We examined relations between early alcohol use and subsequent
      alcohol and sexual risk behaviors among urban adolescents. METHODS: A total of
      1034 African American and Hispanic youths completed surveys assessing alcohol and
      sexual behaviors at 7th and 10th grade. After we controlled for early sexual
      initiation, we examined relations between early drinking and subsequent alcohol
      and sexual behaviors. RESULTS: Early drinking was associated with alcohol and
      sexual risks through mid-adolescence. Early drinkers were more likely to report
      subsequent alcohol problems, unprotected sexual intercourse, multiple partners,
      being drunk or high during sexual intercourse, and pregnancy. Among females,
      early drinking was also related to sexual initiation and recent sexual
      intercourse. CONCLUSIONS: Prevention programs should address combined risks of
      early alcohol use and sexual intercourse, especially where levels of HIV and
      other sexually transmitted infections are elevated.

PMID- 15855471
TI  - Parental and school correlates of binge drinking among middle school students.
AB  - OBJECTIVES: We examined the prevalence and dynamics of binge drinking among
      middle school students. METHODS: We analyzed data from the National Longitudinal
      Study of Adolescent Health. The sample was composed of approximately 5300 seventh
      and eighth-grade students who were interviewed at 2 points in time. RESULTS:
      Approximately 8% of seventh graders and 17% of eighth graders reported engaging
      in binge drinking during the past 12 months. These rates varied as a function of
      school characteristics. Low scores on the parenting variables-communication
      quality, use of reasoning, and control and supervision-and binge drinking during
      middle school also were predictive of binge drinking during high school.
      CONCLUSIONS: Binge drinking among middle school students is an important
      phenomenon that for many students forecasts future binge drinking during high
      school.

PMID- 15855472
TI  - Hepatitis A--related mortality in California, 1989-2000: analysis of multiple
      cause-coded death data.
AB  - OBJECTIVES: We estimated the hepatitis A (HA) mortality rate in California,
      assessed demographic differences in HA-related mortality, and examined
      comorbidities listed on death certificates in order to provide information for
      health policy and planning related to HA vaccination. METHODS: We identified HA
      related deaths in California from 1989 to 2000 with multiple-cause-of-death files
      and calculated mortality rates and rate ratios. RESULTS: We identified 402 HA
      related deaths between 1989 and 2000; the annual age-adjusted HA-related
      mortality rate was 1.20 deaths per 1 million persons. Older individuals, men,
      Latinos, and American Indians/Alaska Natives had elevated mortality rates. Liver
      conditions and non-A viral hepatitis infections were more common among HA-related
      deaths than among all other deaths. CONCLUSIONS: Current immunization practices
      should be reevaluated and the expansion of current vaccination guidelines for
      groups that have elevated HA-related mortality rates should be considered.

PMID- 15855474
TI  - Inherited coagulation factor abnormalities: a pediatric review.
AB  - Clotting factor abnormalities in children provide an interesting challenge to the
      medical care team. Understanding the diagnostic process and the medical
      management of children with factor abnormalities is crucial, as life-threatening
      complications can occur. This article will familiarize the reader with symptoms,
      laboratory testing, diagnosis, and treatment of hereditary coagulation factor
      abnormalities.

PMID- 15855475
TI  - Chronic refractory ITP in children: beyond splenectomy.
AB  - Idiopathic (or immune) thrombocytopenic purpura (ITP) is a relatively common
      hematologic condition, but one that the hematology community has failed to reach
      a consensus on with regard to treatment. In patients with chronic refractory ITP,
      there is even less agreement about treatment approaches, as this population
      represents a small, but challenging, fraction of the total cases of ITP. The aim
      of this article is to review the treatment options available for children with
      chronic refractory ITP, including a review of the benefits versus risks, rate of
      remission, and areas of ongoing and future research.

PMID- 15855476
TI  - Trends in complete blood count values during acute painful episodes in children
      with sickle cell disease.
AB  - Complete blood count (CBC) values are monitored as crude indicators of the
      hemolytic and inflammatory processes that accompany an acute painful episode in
      children with sickle cell disease. As part of a larger study that examined the
      pain experience and pain management of hospitalized children during painful vaso
      occlusive episodes, the authors examined trends in CBC values and determined
      whether there were relationships between these values and pain intensity scores.
      Children, 5 to 19 years of age, with sickle cell disease whose primary reason for
      admission was vasoocclusive pain were recruited for participation in the study.
      Once every evening from the day of admission until the day of discharge, they
      were asked to rate their worst and least pain using the numeric rating scale of
      the African American Oucher pain scale. Complete blood count values were obtained
      from the hospital information system on a daily basis. Parallel changes in CBC
      values and pain intensity scores were evident within the first 48 hours of
      hospitalization. However, although the inflammatory and hemolytic processes were
      resolving, pain persisted at moderate levels throughout the course of
      hospitalization.

PMID- 15855477
TI  - Neurocognitive sequelae of sickle cell disease: current issues and future
      directions.
AB  - Sickle cell disease is a genetic disorder with an autosomal recessive pattern of
      inheritance. This disease is most prevalent among those of African American and
      Mediterranean descent. Cerebral vascular accident (CVA) or stroke is one of the
      major complications of hemoglobin SS (Hgb SS) disease. CVA has implications for
      physical as well as neurocognitive function for children. Recent literature
      suggests that some children with sickle cell disease without overt signs of CVA
      may still have evidence of neurological deficit, both on magnetic resonance
      imaging and neurological examination. There is a growing body of knowledge that
      further aids in delineation of risk factors for CVA, silent infarct, and
      neurocognitive deficits in children with Hgb SS disease. More research is needed
      to continue to explore avenues for identification and intervention. The purpose
      of this article is to delineate areas of ongoing research in this important area.

PMID- 15855478
TI  - Neonatal hematologic disorders.
AB  - Neonatal hematology is a complex subspecialty of pediatric hematology, combining
      the unique aspects of the maternal/fetal relationship, the delicate balance of
      coagulation factors, and the distinctive physiologic conditions of the newborn
      period. The objective of this article is to briefly review specific hematologic
      disorders that commonly present in the newborn period. Alloimmune cytopenias,
      polycythemia, thrombosis and bleeding associated with vitamin K deficiency will
      be discussed through a focus on pathophysiology, signs and symptoms, current
      treatment strategies, and implications for nursing care.

PMID- 15855479
TI  - Factor V Leiden and its effect on children with cardiac pathology.
AB  - Factor V Leiden thrombophilia, formed by a genetic mutation, slows the body's
      anticoagulation response to clot formation. First described in 1994, factor V
      Leiden mutation has been identified as a contributing risk factor for venous
      thromboembolism. Although venous thromboembolism is considered rare in the
      pediatric population, Factor V Leiden has implications for certain at-risk
      pediatric patients.

PMID- 15855480
TI  - Changing patterns in the selection of viral mutations among patients receiving
      nucleoside and nucleotide drug combinations directed against human
      immunodeficiency virus type 1 reverse transcriptase.

PMID- 15855481
TI  - Antileishmanial activity of the terpene nerolidol.
AB  - The activity of nerolidol, a sesquiterpene used as a food-flavoring agent and
      currently under testing as a skin penetration enhancer for the transdermal
      delivery of therapeutic drugs, was evaluated against Leishmania species.
      Nerolidol inhibited the growth of Leishmania amazonensis, L. braziliensis, and L.
      chagasi promastigotes and L. amazonensis amastigotes with in vitro 50% inhibitory
      concentrations of 85, 74, 75, and 67 microM, respectively. The treatment of L.
      amazonensis-infected macrophages with 100 microM nerolidol resulted in 95%
      reduction in infection rates. Inhibition of isoprenoid biosynthesis, as shown by
      reduced incorporation of [2-(14)C]mevalonic acid (MVA) or [1-(14)C]acetic acid
      precursors into dolichol, ergosterol, and ubiquinone, was observed in nerolidol
      treated promastigotes. This drug effect can be attributed to the blockage of an
      early step in the mevalonate pathway, since incorporation of the precursor [1(n)
      (3)H]farnesyl pyrophosphate in polyisoprenoids is not inhibited by nerolidol. L.
      amazonensis-infected BALB/c mice were treated with intraperitoneal doses of 100
      mg/kg/day for 12 days or topically with 5 or 10% ointments for 4 weeks.
      Significant reduction of lesion sizes in nerolidol treated mice was observed for
      both treatment routes. However, long-term follow up indicated that the disease
      was not cured in this highly susceptible animal model. Nonetheless, the in vitro
      activity of nerolidol against these parasites may prove a useful tool for the
      development of new drugs for the treatment of leishmaniasis. In addition,
      biosynthesis of dolichols with 11 and 12 isoprene units was identified in
      Leishmania, as described for other trypanosomatids and Apicomplexa.

PMID- 15855482
TI  - Molecular characterization of vanB elements in naturally occurring gut anaerobes.
AB  - Previously, we reported the isolation of 10 vancomycin-resistant gram-positive
      anaerobic bacilli carrying the vanB ligase gene from nine hemodialysis patients
      (S. A. Ballard et al., Antimicrob. Agents Chemother. 49:77-81, 2005; T. P.
      Stinear et al., Lancet 357:855-856, 2001). In the present study, the molecular
      and evolutionary relationship of the vanB resistance element within these 10
      anaerobes and two vancomycin-resistant Enterococcus faecium strains were
      examined. PCR analysis and nucleotide sequencing demonstrated that all 12
      isolates carried the vanB operon associated with an element identical to Tn1549
      and Tn5382 of Enterococcus. Restriction fragment length polymorphism analysis of
      the vanB operon in these isolates revealed two distinct patterns, and sequencing
      showed that minor base differences existed. PCR amplification of the joint region
      of a circular intermediate was demonstrated in nine of these organisms, a finding
      indicative of an ability to excise and circularize, an intermediate step in
      transposition and conjugative transfer. Southern hybridization with a vanB
      vanX(B) probe suggests that there is one insert of the transposon in all
      isolates. Sequence analysis of the integration site revealed distinct sequences:
      the Tn1549/5382 element within E. faecium was inserted within the host
      chromosome, whereas nucleotide sequences surrounding the Tn1549/5382 element in
      the 10 anaerobes showed no significant homology to sequences in the GenBank
      database. We demonstrate considerable similarity between the Tn1549/5382 element
      identified in 10 anaerobe isolates with that found in enterococci. The homology
      and potential to transpose suggest a recent horizontal transfer event may have
      occurred. However, the original direction of transposition and the mechanism
      involved remains unknown.

PMID- 15855483
TI  - Mixed-lipid storage disorder induced in macrophages and fibroblasts by
      oritavancin (LY333328), a new glycopeptide antibiotic with exceptional cellular
      accumulation.
AB  - Oritavancin, a semisynthetic derivative of vancomycin endowed with a cationic
      amphiphilic character, accumulates to large extent in the lysosomes of eukaryotic
      cells (F. Van Bambeke, S. Carryn, C. Seral, H. Chanteux, D. Tyteca, M. P. Mingeot
      Leclercq, and P. M. Tulkens, Antimicrob. Agents Chemother. 48:2853-2860, 2004).
      In the present study, we examined whether this accumulation could cause cell
      alterations in phagocytic (J774 mouse macrophages) and nonphagocytic (rat embryo
      fibroblasts) cells exposed to clinically meaningful (0- to 40-mg/liter)
      concentrations of oritavancin. Optical and electronic microscopy evidenced
      conspicuous alterations of the vacuolar apparatus in both cell types,
      characterized by the deposition of concentric lamellar structures, finely
      granular material, or other less-defined osmiophilic material, often deposed in
      giant vesicles. Biochemical studies showed an accumulation of phospholipids (1.5
      x control values) and free and esterified cholesterol (3 to 4 x control values
      for total cholesterol). Accumulation of these lipids was in close relation to
      that of oritavancin (excess phospholipid/oritavancin and excess
      cholesterol/oritavancin molar ratios of 2 to 3 and 3 to 5, respectively).
      Cholesterol accumulation was rapid and reversible, and that of phospholipids was
      slower and poorly reversible. Vancomycin and teicoplanin, used as controls (50
      and 100 mg/liter, respectively), did not cause any significant change in the
      lipid content of fibroblasts. The data therefore suggest that oritavancin has the
      potential to cause a mixed-lipid storage disorder in eukaryotic cells.

PMID- 15855484
TI  - Antifungal therapy of experimental cerebral phaeohyphomycosis due to
      Cladophialophora bantiana.
AB  - Cladophialophora bantiana is associated with central nervous system infection and
      a poor outcome. C. bantiana tends to be resistant to amphotericin B. Accordingly,
      we evaluated amphotericin B and three triazoles--posaconazole, itraconazole, and
      fluconazole--for treatment of C. bantiana infection in mice. In immunosuppressed
      ICR mice infected intravenously, posaconazole, itraconazole, and amphotericin B
      prolonged survival. This improvement in survival corresponded with a reduction in
      brain fungal concentrations for mice which were given itraconazole and
      posaconazole, but not amphotericin B. In nonimmunosuppressed BALB/c mice infected
      intracerebrally, posaconazole showed dose-dependent responses in survival and
      reduction of brain tissue counts. These responses were observed for short,
      delayed, and prolonged therapy. Although posaconazole prolonged the survival of
      mice with reductions in brain fungal counts, it did not sterilize brain tissue
      with continuous therapy for 8 weeks. We concluded that posaconazole shows promise
      for the treatment of C. bantiana brain infections.

PMID- 15855485
TI  - Genetic environment and expression of the extended-spectrum beta-lactamase blaPER
      1 gene in gram-negative bacteria.
AB  - The genetic location of the gene coding for the expanded-spectrum beta-lactamase
      PER-1 was analyzed in a series of gram-negative isolates. It was identified as
      part of a composite transposon bracketed by two novel insertion elements, ISPa12
      and ISPa13, belonging to the IS4 family that possess transposases that share 63%
      amino acid identity and that are chromosomally located in Pseudomonas aeruginosa,
      Providencia stuartii, and Acinetobacter baumannii. On the contrary, the bla(PER
      1) gene was identified just downstream of an ISPa12 element but not within a
      composite transposon when it was located on a plasmid in Salmonella enterica
      serovar Typhimurium and A. baumannii isolates. In both cases, expression of the
      bla(PER-1) gene was driven by promoter sequences located in ISPa12.

PMID- 15855486
TI  - Relationship between mutations in the gyrA gene and quinolone resistance in
      clinical isolates of Corynebacterium striatum and Corynebacterium amycolatum.
AB  - Quinolone susceptibility was analyzed in 17 clinical isolates of Corynebacterium
      striatum and 9 strains of Corynebacterium amycolatum by the E-test method in
      Mueller-Hinton agar plates. The C. striatum ATCC 6940 strain was used as a
      control strain. The amplified quinolone resistance determining regions of the
      gyrA genes of C. amycolatum and C. striatum were characterized. Four in vitro
      quinolone-resistant mutants of C. amycolatum were selected and analyzed. Both in
      vivo and in vitro quinolone-resistant strains of C. amycolatum showed high levels
      of fluoroquinolone resistance in strains with a double mutation leading to an
      amino acid change in positions 87 and 91 or positions 87 and 88 (unusual
      mutation) of GyrA, whereas the same concomitant mutations at amino acid positions
      87 and 91 in GyrA of C. striatum produced high levels of resistance to
      ciprofloxacin and levofloxacin but only showed a moderate increase in the MIC of
      moxifloxacin, suggesting that other mechanism(s) of quinolone resistance could be
      involved in moxifloxacin resistance in C. amycolatum. Moreover, a PCR-RFLP-NcoI
      of the gyrA gene was developed to distinguish between C. amycolatum and C.
      striatum species.

PMID- 15855487
TI  - Virological and pharmacological parameters predicting the response to lopinavir
      ritonavir in heavily protease inhibitor-experienced patients.
AB  - The genotypic inhibitory quotient (GIQ) has been proposed as a way to integrate
      drug exposure and genotypic resistance to protease inhibitors and can be useful
      to enhance the predictivity of virologic response for boosted protease
      inhibitors. The aim of this study was to evaluate the predictivity of the GIQ in
      116 protease inhibitor-experienced patients treated with lopinavir-ritonavir. The
      overall decrease in human immunodeficiency virus type 1 (HIV-1) RNA from baseline
      to month 6 was a median of -1.50 log(10) copies/ml and 40% of patients had plasma
      HIV-1 RNA below 400 copies/ml at month 6. The overall median lopinavir study
      state C(min) concentration was 5,856 ng/ml. Using univariate linear regression
      analyses, both lopinavir GIQ and the number of baseline lopinavir mutations were
      highly associated with virologic response through 6 months. In the multivariate
      analysis, only lopinavir GIQ, baseline HIV RNA, and the number of prior protease
      inhibitors were significantly associated with response. When the analysis was
      limited to patients with more highly mutant viruses (three or more lopinavir
      mutations), only lopinavir GIQ remained significantly associated with virologic
      response. This study suggests that GIQ could be a better predictor of the
      virologic response than virological (genotype) or pharmacological (minimal plasma
      concentration) approaches used separately, especially among patients with at
      least three protease inhibitor resistance mutations. Therapeutic drug monitoring
      for patients treated by lopinavir-ritonavir would likely be most useful in
      patients with substantially resistant viruses.

PMID- 15855488
TI  - Immunomodulatory activities of small host defense peptides.
AB  - Recent studies have demonstrated that in addition to their antimicrobial
      activity, cationic host defense peptides, like the human cathelicidin LL-37,
      perform many activities relating to innate immunity, including the induction or
      modulation of chemokine and cytokine production, alteration of gene expression in
      host cells, and inhibition of proinflammatory responses of host cells to
      bacterial components such as lipopolysaccharide (LPS) in vitro and in vivo. To
      investigate if these properties are shared by smaller peptides, two cathelicidin
      peptides derived from bovine neutrophils, the 13-mer indolicidin and Bac2A, a
      linear 12-amino-acid derivative of bactenecin, were compared to the 37-amino-acid
      peptide LL-37. Indolicidin, like LL-37, inhibited LPS-induced tumor necrosis
      factor alpha (TNF-alpha) secretion, even when added up to an hour after the
      addition of Escherichia coli O111:B4 LPS to the human macrophage/monocyte-like
      THP-1 cell line. In contrast, Bac2A demonstrated no significant antiendotoxin
      activity. At low concentrations, indolicidin and LL-37 acted synergistically to
      suppress LPS-induced production of TNF-alpha. Indolicidin was analogous to LL-37
      in its ability to induce the production of the chemokine interleukin-8 (IL-8) in
      a human bronchial cell line, 16HBE14o(-), but it was unable to induce production
      of IL-8 in THP-1 cells. In contrast, Bac2A was unable to induce IL-8 in either
      cell type. Conversely, Bac2A was chemotactic for THP-1 cells at concentrations
      between 10 and 100 mug/ml, while indolicidin and LL-37 were not chemotactic at
      these concentrations for THP-1 cells. This indicates that in addition to the
      potential for direct microbicidal activity, cationic host defense peptides may
      have diverse and complementary abilities to modulate the innate immune response.

PMID- 15855489
TI  - Should we use N-acetyltransferase type 2 genotyping to personalize isoniazid
      doses?
AB  - Isoniazid is metabolized by the genetically polymorphic arylamine N
      acetyltransferase type 2 (NAT2). A greater number of high-activity alleles are
      related to increased acetylation capacity and in some reports to low efficacy and
      toxicity of isoniazid. The objective of this study was to assess individual
      isoniazid exposure based on NAT2 genotype to predict a personalized therapeutic
      dose. Isoniazid was administered to 18 healthy Caucasians (age 30 +/- 6 years,
      body weight 74 +/- 10 kg, five women) in random order as a 200-mg infusion, a 100
      mg oral, and a 300-mg oral single dose. For the assessment of NAT2 genotype,
      common single nucleotide polymorphisms identifying 99.9% of variant alleles were
      characterized. Noncompartmental pharmacokinetics and compartmental population
      pharmacokinetics were estimated from isoniazid plasma concentrations until 24 h
      postdose by high-pressure liquid chromatography. The influence of NAT2 genotype,
      drug formulation, body weight, and sex on dose-normalized isoniazid
      pharmacokinetics was assessed by analysis of variance from noncompartmental data
      and confirmed by population pharmacokinetics. Eight high-activity NAT2*4 alleles
      were identified. Sex had no effect; the other factors explained 93% of the
      variability in apparent isoniazid clearance (analysis of variance). NAT2 genotype
      alone accounted for 88% of variability. Individual isoniazid clearance could be
      predicted as clearance (liters/hour) = 10 + 9 x (number of NAT2*4 alleles). To
      achieve similar isoniazid exposure, current standard doses presumably appropriate
      for patients with one high-activity NAT2 allele may be decreased or increased by
      approximately 50% for patients with no or two such alleles, respectively.
      Prospective clinical trials are required to assess the merits of this approach.

PMID- 15855490
TI  - Clinically relevant genotype interpretation of resistance to didanosine.
AB  - We analyzed the didanosine (ddI) arm of the randomized, placebo-controlled Jaguar
      trial in order to define a genotypic score for ddI associated with virologic
      response. In this arm, 111 patients experiencing virologic failure received ddI
      in addition to their current combination therapy for 4 weeks. The impact of
      mutations in the reverse transcriptase gene on the virologic response to ddI was
      studied in univariate analysis. Genotypic score was constructed using step-by
      step analyses first including only mutations associated to poorer virologic
      response (scored as +1), while secondarily, mutations associated to a better
      response (scored as -1) were also eligible. Eight mutations were associated with
      a reduced response to ddI, M41L, D67N, T69D, L74V, V118I, L210W, T215Y/F, and
      K219Q/E, and two mutations were associated with a better response, K70R and
      M184V/I. The best prediction of the virologic response to ddI was obtained with a
      composite score comprising mutations added and subtracted (set II, M41L + T69D +
      L74V+ T215Y/F + K219Q/E - K70R - M184V/I; P = 4.5 x 10(-9)) and by comparing that
      to only mutations added (set I, M41L + T69D + L74V + L210W + T215Y/F + K219Q/E; P
      = 1.2 x 10(-7)). Patients had a human immunodeficiency virus RNA reduction of
      1.24, 0.84, 0.61, 0.40, and 0.07 log(10) copies/ml when they were ranked as
      having a genotypic score II of -2, -1, or 0 or 1 and 2 mutations or more,
      respectively. In conclusion, we developed and validated a genotypic score, taking
      into account mutations negatively and positively impacting the virologic response
      to ddI.

PMID- 15855491
TI  - Candida albicans zinc cluster protein Upc2p confers resistance to antifungal
      drugs and is an activator of ergosterol biosynthetic genes.
AB  - The human pathogen Candida albicans is responsible for a large proportion of
      infections in immunocompromised individuals, and the emergence of drug-resistant
      strains is of medical concern. Resistance to antifungal azole compounds is often
      due to an increase in drug efflux or an alteration of the pathway for synthesis
      of ergosterol, an important plasma membrane component in fungi. However, little
      is known about the transcription factors that mediate drug resistance. In
      Saccharomyces cerevisiae, two highly related transcriptional activators, Upc2p
      and Ecm22p, positively regulate the expression of genes involved in ergosterol
      synthesis (ERG genes). We have identified a homologue in C. albicans of the S.
      cerevisiae UPC2/ECM22 genes and named it UPC2. Deletion of this gene impaired
      growth under anaerobic conditions and rendered cells highly susceptible to the
      antifungal drugs ketoconazole and fluconazole. Conversely, overexpression of
      Upc2p increased resistance to ketoconazole, fluconazole, and fluphenazine. Azole
      induced expression of the ERG genes was abolished in a Delta upc2 strain, while
      basal levels of these mRNAs remained unchanged. Importantly, the purified DNA
      binding domain of Upc2p bound in vitro to putative sterol response elements in
      the ERG2 promoter, suggesting that Upc2p increases the expression of the ERG
      genes by directly binding to their promoters. These results provide an important
      link between changes in the ergosterol biosynthetic pathway and azole resistance
      in this opportunistic fungal species.

PMID- 15855492
TI  - In vitro assessment of the further potential for development of fluoroquinolone
      resistance in Neisseria meningitidis.
AB  - We examined the potential for the development of fluoroquinolone resistance in
      Neisseria meningitidis by cultivating two clinical isolates of meningococci in
      the presence of concentrations of ciprofloxacin at and about the predetermined
      MIC. The quinolone resistance determining regions (QRDRs) of gyrA and parC of 50
      stable quinolone-resistant mutants derived in vitro were sequenced and compared
      with QRDR alterations reported in clinical isolates of quinolone-resistant
      meningococci and gonococci. MICs to ciprofloxacin and trovafloxacin were
      determined and sequence changes were correlated with quinolone MICs.
      Ciprofloxacin and trovafloxacin MICs of the in vitro-derived quinolone-resistant
      mutants ranged up to 16 mg/liter. Single GyrA alterations were the first change
      detected and were accompanied by raised MICs, followed by double GyrA changes and
      still higher MICs. MICs increased further as single ParC substitutions appeared
      and these were always in the presence of a single or double GyrA change. GyrA
      changes occurred at positions 91 and 95 with substitutions of Asp-95-->Asn and
      Thr-91-->Ala and Ile. Changes in the parC QRDR occurred at positions 85, 86, and
      91 with four substitutions, Gly-85-->Asp, Asp-86-->Asn, Glu-91-->Gly, and Glu-91-
      >Lys, detected. The nature of the individual QRDR substitution appeared to
      influence the level of quinolone resistance expressed, and this varied with the
      quinolone agent examined. Close similarities occurred between the sequence and
      nature of QRDR changes in clinical and in vitro-generated quinolone-resistant
      mutants and with those previously reported for clinical and in vitro-generated
      quinolone-resistant gonococci. This suggests that quinolone resistance in
      meningococci may arise in the same manner and reach similar levels in vivo to
      those seen in quinolone-resistant Neisseria gonorrhoeae.

PMID- 15855493
TI  - Intracellular substrates for the primer-unblocking reaction by human
      immunodeficiency virus type 1 reverse transcriptase: detection and quantitation
      in extracts from quiescent- and activated-lymphocyte subpopulations.
AB  - Treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients with
      3'-azido-3'-deoxythymidine (AZT) selects for mutant forms of viral reverse
      transcriptase (RT) with increased ability to remove chain-terminating nucleotides
      from blocked DNA chains. We tested various cell extracts for the presence of
      endogenous acceptor substrates for this reaction. Cell extracts incubated with
      HIV-1 RT and [(32)P]ddAMP-terminated DNA primer/template gave rise to (32)P
      labeled adenosine 2',3'-dideoxyadenosine 5',5'''-P(1),P(4)-tetraphosphate
      (Ap(4)ddA), ddATP, Gp(4)ddA, and Ap(3)ddA, corresponding to the transfer of
      [(32)P]ddAMP to ATP, PP(i), GTP, and ADP, respectively. Incubation with
      [(32)P]AZT monophosphate (AZTMP)-terminated primer/template gave rise to the
      analogous (32)P-labeled AZT derivatives. Based on the rates of formation of the
      specific excision products, ATP and PP(i) levels were determined: ATP was present
      at 1.3 to 2.2 mM in H9 cells, macrophages, and unstimulated CD4(+) or CD8(+) T
      cells, while PP(i) was present at 7 to 15 microM. Under these conditions, the ATP
      dependent reaction predominated, and excision by the AZT-resistant mutant RT was
      more efficient than wild type RT. Activated CD4(+) or CD8(+) T cells contained
      1.4 to 2.7 mM ATP and 55 to 79 microM PP(i). These cellular PP(i) concentrations
      are lower than previously reported; nonetheless, the PP(i)-dependent reaction
      predominated in extracts from activated T cells, and excision by mutant and wild
      type RT occurred with similar efficiency. While PP(i)-dependent excision may
      contribute to AZT resistance in vivo, it is likely that selection of AZT
      resistant mutants occurs primarily in an environment where the ATP-dependent
      reaction predominates.

PMID- 15855494
TI  - Biphasic effects of geranylgeraniol, teprenone, and phytol on the growth of
      Staphylococcus aureus.
AB  - We examined the antibacterial activities against Staphylococcus aureus of three
      diterpenes, namely, geranylgeraniol, teprenone, and phytol, by using a broth
      dilution with shaking method to identify the effects of diterpenes with long
      aliphatic carbon chains. We also performed time-kill assays and measured the
      leakage of K(+) ions from bacterial cells in response to these diterpenes. The
      diterpenes used inhibited the growth of S. aureus at concentrations of 0.15
      microg/ml, as determined by damage to the cell membranes, and had clear
      bactericidal activity. However, the inhibitory effects of the diterpenes
      decreased when the concentration of each was raised above a certain level. The
      diterpenes tested in this study appeared to have both growth-inhibitory and
      growth-accelerating effects, and the net effect of each depended on its
      concentration.

PMID- 15855495
TI  - Application of an in vitro infection model and simulation for reevaluation of
      fluoroquinolone breakpoints for Salmonella enterica serotype typhi.
AB  - Salmonella enterica serotype Typhi and nontyphoidal Salmonella remain major
      causes of morbidity and mortality worldwide. Ampicillin, trimethoprim
      sulfamethoxazole, and chloramphenicol no longer provide reliable coverage of
      Salmonella, and fluoroquinoloes have emerged as first-line treatment options. Due
      to mounting evidence of decreased in vitro susceptibility and diminished clinical
      response to fluoroquinolone therapy, it has been suggested that the NCCLS
      breakpoints for the salmonellae be reevaluated. We utilized an in vitro infection
      model to determine which pharmacokinetic-pharmacodynamic (PK-PD) measure was most
      closely linked to fluoroquinolone activity against salmonellae and the magnitude
      that was predictive of efficacy. Monte Carlo simulation was utilized to determine
      the probability of attaining potential susceptibility breakpoints for three
      fluoroquinolones. The free-drug area under the concentration-time curve from 0 to
      24 h/MIC ratio was the PK-PD measure most predictive of efficacy, and a ratio of
      105 corresponded to 90% of maximal activity. Simulation results suggested
      susceptible breakpoints of 0.12 microg/ml for ciprofloxacin and gatifloxacin and
      0.25 microg/ml for levofloxacin. These proposed breakpoints correspond to the MIC
      separating the wild-type susceptible organism population from those strains
      possessing single-step mutations in the quinolone resistance-determining region.
      These results that integrate PK-PD measures and fluoroquinolone MIC distributions
      in the genetic context of examined Salmonella isolates clearly demonstrate that
      the prudent use of a lower susceptibility breakpoint minimizes the probability of
      clinical failure or delayed response in fluoroquinolone-treated patients.

PMID- 15855496
TI  - Mutations in PA3574 (nalD) lead to increased MexAB-OprM expression and multidrug
      resistance in laboratory and clinical isolates of Pseudomonas aeruginosa.
AB  - Mutations in genes mexR and nalC have previously been shown to drive
      overexpression of the MexAB-OprM multidrug efflux system in Pseudomonas
      aeruginosa. A transposon insertion multidrug-resistant mutant of P. aeruginosa
      overproducing MexAB-OprM was disrupted in yet a third gene, PA3574, encoding a
      probable repressor of the TetR/AcrR family that we have dubbed NalD. Clinical
      strains overexpressing MexAB-OprM but lacking mutations in mexR or nalC were also
      shown to carry mutations in nalD. Moreover, the cloned nalD gene reduced the
      multidrug resistance and MexAB-OprM expression of the transposon mutant and
      clinical isolates, highlighting the significance of the nalD mutations vis-a-vis
      MexAB-OprM overexpression in these isolates.

PMID- 15855497
TI  - Bactericidal activity of first-choice antibiotics against gamma interferon
      induced persistent infection of human epithelial cells by Chlamydia trachomatis.
AB  - Chlamydia trachomatis is responsible for clinically important chronic
      inflammatory diseases of humans, including trachoma and pelvic inflammatory
      disease. Persistent infection of mucosal sites may contribute to the development
      of these chronic inflammatory diseases. Standard clinical therapy results in
      satisfactory cure rates of acute infections; however, chronic infection
      associated with persistence has been suggested to be less responsive to
      antibiotic therapy. We report the efficiency of two first-line chlamydial
      antibiotics, azithromycin and doxycycline, under conditions of eradication of C.
      trachomatis persistent infection using the in vitro model of gamma interferon
      (IFN-gamma)-mediated persistence and reactivation from persistence. Doxycycline
      was superior in eradicating acute (minimal bactericidal concentration [MBC](100)
      = 2.5 to 5.0 microg/ml) compared to persistent (MBC(100) = 10 to 50 mirog/ml)
      infection. In contrast, azithromycin was significantly more effective in
      eradicating persistent infection (MBC(100) = 2.5 to 5.0 microg/ml) than acute
      infection (MBC(100) = 10 to 50 microg/ml). The superior bactericidal effect of
      azithromycin against persistent infection was found to correlate with the
      enhanced uptake of the drug by IFN-gamma-treated infected epithelial cells. Based
      on these findings, we hypothesize that azithromycin should be a particularly
      efficacious anti-infective agent for the eradication of IFN-gamma-induced
      chlamydial persistent infection in vivo.

PMID- 15855498
TI  - Inhibitory effect of aureobasidin A on Toxoplasma gondii.
AB  - The apicomplexan parasite Toxoplasma gondii is a leading opportunistic pathogen
      associated with AIDS and congenital birth defects. Due to the need for
      identifying new parasite-specific treatments, the possibility of targeting
      sphingolipid biosynthesis in the parasite was investigated. Aureobasidin A, an
      inhibitor of the enzyme synthesizing the sphingolipid inositol
      phosphorylceramide, which is present in fungi, plants, and some protozoa but
      absent in mammalian cells, was found to block in vitro T. gondii replication
      without affecting host cell metabolism. Aureobasidin A treatment did not induce
      tachyzoite to bradyzoite stage conversion in T. gondii but resulted in a loss of
      intracellular structures and vacuolization within the parasite. In addition,
      aureobasidin A inhibited sphingolipid synthesis in T. gondii. Sphingolipid
      biosynthetic pathways may therefore be considered targets for the development of
      anti-T. gondii agents.

PMID- 15855499
TI  - Incidence of class 1 integrons in a quaternary ammonium compound-polluted
      environment.
AB  - Samples of effluent and soil were collected from a reed bed system used to
      remediate liquid waste from a wool finishing mill with a high use of quaternary
      ammonium compounds (QACs) and were compared with samples of agricultural soils.
      Resistance quotients of aerobic gram-negative and gram-positive bacteria to
      ditallowdimethylammomium chloride (DTDMAC) and cetyltrimethylammonium bromide
      (CTAB) were established by plating onto nutrient agar containing 5 microg/ml or
      50 microg/ml DTDMAC or CTAB. Approximately 500 isolates were obtained and
      screened for the presence of the intI1 (class 1 integrase), qacE (multidrug
      efflux), and qacE Delta1 (attenuated qacE) genes. QAC resistance was higher in
      isolates from reed bed samples, and class 1 integron incidence was significantly
      higher for populations that were preexposed to QACs. This is the first study to
      demonstrate that QAC selection in the natural environment has the potential to
      coselect for antibiotic resistance, as class 1 integrons are well-established
      vectors for cassette genes encoding antibiotic resistance.

PMID- 15855500
TI  - Phase 1 safety and pharmacokinetic study of chimeric murine-human monoclonal
      antibody c alpha Stx2 administered intravenously to healthy adult volunteers.
AB  - Hemolytic-uremic syndrome (HUS) is a serious complication of infection by Shiga
      toxin-producing Escherichia coli. Shiga toxin type 2 (Stx2) is responsible for
      the renal toxicity that can follow intestinal infection and hemorrhagic colitis
      due to E. coli. A chimeric mouse-human antibody, designated c alpha Stx2, that
      has neutralizing activity in a mouse model was produced and tested in healthy
      adult volunteers. In this phase I dose escalation study, c alpha Stx2 was
      generally well tolerated. Pharmacokinetic studies indicated that clearance was
      stable over the dose range of 1.0 to 10 mg/kg of body weight (0.249 +/- 0.023
      ml/kg/h) but was higher for the 0.1-mg/kg dose (0.540 +/- 0.078 ml/kg/h),
      suggesting saturable elimination. A similar nonlinear trend was observed for the
      volume of distribution, where average values ranged from 0.064 +/- 0.015 liter/kg
      for the 1.0- to 10-mg/kg doses and 0.043 +/- 0.005 for the 0.01-mg/kg dose. The
      relatively small volume of distribution suggests that the antibody is limited to
      the vascular (plasma) compartment. The mean half-life was 165 +/- 66 h, with
      lowest values observed for the 0.1-mg/kg dose (56.2 +/- 9.7 h) and the highest
      values reported for the 10.0-mg/kg dose (206.4 +/- 12.4 h). Future studies are
      needed to confirm the safety of this c alpha Stx2, and innovative clinical trials
      will be required to measure its efficacy in preventing or treating HUS.

PMID- 15855501
TI  - Clinical pharmacokinetics of alamifovir and its metabolites.
AB  - Alamifovir, a purine nucleotide analogue prodrug, and its hydrolyzed derivatives
      have shown preclinical efficacy activity against wild-type and lamivudine
      resistant hepatitis B virus. Two studies were conducted to examine the single-
      and multiple-dose alamifovir pharmacokinetics after oral administration in
      healthy males. In study 1, subjects were given single doses (0.2 to 80 mg), with
      a subset receiving 20 mg in a fed state. Study 2 subjects were dosed with 2.5 to
      15 mg twice daily for 15 days. Plasma samples were collected over 72 h in study 1
      and over 24 h on days 1 and 15 in study 2. Concentrations of alamifovir and its
      major metabolites were determined using liquid chromatography/tandem mass
      spectrometry methods. The data were analyzed using a noncompartmental technique.
      Although alamifovir was rapidly absorbed, there was limited systemic exposure due
      to its rapid hydrolysis and formation of at least three metabolites, suggesting
      that alamifovir acts as a prodrug. The major metabolites detected were 602074 and
      602076, with 602075 detectable only in higher-dose groups. Maximum 602074 plasma
      concentration was achieved at approximately 0.5 h (T(max)) and declined with a 1-
      to 2-h terminal half-life (t(1/2)). Maximum concentrations of 602076 (C(max))
      averaged 10% of the 602074 C(max) and reached T(max) in 2.5 h with a 4-h t(1/2).
      Food appeared to decrease the extent of absorption of the compound. Multiple
      dosing resulted in minimal accumulation, and the concentrations following
      multiple doses could be predicted using the single-dose data. Alamifovir was well
      tolerated and the pharmacokinetics were characterized in these studies.

PMID- 15855502
TI  - Integron content of extended-spectrum-beta-lactamase-producing Escherichia coli
      strains over 12 years in a single hospital in Madrid, Spain.
AB  - The contribution of integrons to the dissemination of extended-spectrum beta
      lactamases (ESBL) was analyzed on all ESBL-producing Escherichia coli isolates
      from 1988 to 2000 at Ramon y Cajal Hospital. We studied 133 E. coli pulsed-field
      gel electrophoresis types: (i) 52 ESBL-producing clinical strains (C-ESBL) (16
      TEM, 9 SHV, 21 CTX-M-9, 1 CTX-M-14, and 5 CTX-M-10); (ii) 43 non-ESBL blood
      clinical strains (C-nESBL); and (iii) 38 non-ESBL fecal isolates from healthy
      volunteers (V-nESBL). Class 1 integrons were more common among C-ESBL (67%) than
      among C-nESBL (40%) or V-nESBL (26%) (P < 0.001) due to the high number of
      strains with bla(CTX-M-9), which is linked to an In6-like class 1 integron.
      Without this bias, class 1 integron occurrence would be similar in C-ESBL and C
      nESBL groups (47% versus 40%). Occurrence of class 2 integrons was similar among
      clinical and community isolates (13 to 18%). No isolates contained class 3
      integrons. The relatively low rate of class 1 integrons within transferable
      elements carrying bla(TEM) (23%) or bla(SHV) (33%) and the absence of class 2
      integrons in all ESBL transconjugants mirror the assembly of translocative pieces
      containing bla(TEM) or bla(SHV) on local available transferable elements lacking
      integrons. The low diversity of class 1 integrons (seven types recovered in all
      groups) might indicate a wide dissemination of specific genetic elements in which
      they are located. In our environment, the spread of genetic elements encoding
      ESBL has no major impact on the dispersion of integrons, nor do integrons have a
      major impact on the spread of ESBL, except when bla(ESBL) genes are within an
      integron platform such as bla(CTX-M-9).

PMID- 15855503
TI  - Combination of candidate microbicides cellulose acetate 1,2-benzenedicarboxylate
      and UC781 has synergistic and complementary effects against human
      immunodeficiency virus type 1 infection.
AB  - The combination of two candidate microbicides, cellulose acetate 1,2
      benzenedicarboxylate (CAP), a polymer that blocks human immunodeficiency virus
      type 1 (HIV-1) entry by targeting gp120 and gp41, and UC781, a tight-binding HIV
      1 reverse transcriptase inhibitor (RTI), resulted in effective synergy for
      inhibition of MT-2 cell infection by HIV-1(IIIB), a laboratory-adapted virus
      strain. The 95% effective concentration values for the combination were reduced
      about 15- to 20-fold compared with those corresponding to the single compounds.
      The combination of CAP and UC781 is also synergistic in inhibiting infection of
      peripheral blood mononuclear cells by a primary HIV-1 isolate, 92US657.
      Combinations of CAP with other RTIs, such as efavirenz or zidovudine, also had
      significant synergistic effects on the inhibition of HIV-1 infection. In
      addition, CAP and UC781 had complementary effects against HIV-1 infection since
      (i) CAP inhibited infection by the UC781-resistant strain HIV-1(IIIB) A17 and
      (ii) pretreatment of MT-2 cells with UC781, but not CAP, abolished subsequent
      infection after removal of the compound. This suggests that the combination of
      CAP and UC781 represents a promising candidate microbicide for prevention of
      sexual transmission of HIV-1.

PMID- 15855505
TI  - Molecular characterization of MexL, the transcriptional repressor of the mexJK
      multidrug efflux operon in Pseudomonas aeruginosa.
AB  - The Pseudomonas aeruginosa mexJK efflux operon is constitutively expressed in
      mutants with defects in the upstream mexL gene, which encodes a repressor of the
      TetR family. MexL and a MexL(A47D) mutant protein were purified from Escherichia
      coli as fusion proteins with carboxy-terminal hexahistidine tags. Native
      polyacrylamide gel electrophoresis and size exclusion chromatography revealed
      that MexL is a tetramer in solution. MexL and MexL(A47D) oligomerization was
      confirmed using a genetic approach, and the MexL(A47D) mutant protein was not
      impaired in multimerization. Gel mobility shift and footprinting assays
      demonstrated that MexL, but not MexL(A47D), binds specifically to the 94-bp mexL
      mexJ intergenic region to sequences located between positions -84 and -20 from
      the mexJ initiation codon. MexL protected about 60 nucleotides on each strand,
      and the protected regions overlapped almost perfectly, a finding consistent with
      MexL regulating the expression of both mexL and mexJK, which was ascertained by
      gene fusion analyses. The protected region contains predicted -10 and -35
      promoter sequences for both mexL and mexJ, with partially overlapping -10
      regions. The mexL promoter assignment was verified by mapping the mexL
      transcription start site, and the mexJ promoter was localized to the predicted
      regions using lacZ fusions. The MexL-protected region contains two inverted
      GTATTT repeats, and their location in the protected region and overlap with the
      mexL and mexJ promoter sequences strongly support a role in MexL binding.

PMID- 15855504
TI  - Imidazole antibiotics inhibit the nitric oxide dioxygenase function of microbial
      flavohemoglobin.
AB  - Flavohemoglobins metabolize nitric oxide (NO) to nitrate and protect bacteria and
      fungi from NO-mediated damage, growth inhibition, and killing by NO-releasing
      immune cells. Antimicrobial imidazoles were tested for their ability to
      coordinate flavohemoglobin and inhibit its NO dioxygenase (NOD) function.
      Miconazole, econazole, clotrimazole, and ketoconazole inhibited the NOD activity
      of Escherichia coli flavohemoglobin with apparent K(i) values of 80, 550, 1,300,
      and 5,000 nM, respectively. Saccharomyces cerevisiae, Candida albicans, and
      Alcaligenes eutrophus enzymes exhibited similar sensitivities to imidazoles.
      Imidazoles coordinated the heme iron atom, impaired ferric heme reduction,
      produced uncompetitive inhibition with respect to O(2) and NO, and inhibited NO
      metabolism by yeasts and bacteria. Nevertheless, these imidazoles were not
      sufficiently selective to fully mimic the NO-dependent growth stasis seen with
      NOD-deficient mutants. The results demonstrate a mechanism for NOD inhibition by
      imidazoles and suggest a target for imidazole engineering.

PMID- 15855506
TI  - Growth cycle-dependent pharmacodynamics of antichlamydial drugs.
AB  - Chlamydiae are obligate intracellular pathogens that exhibit an extensive
      intracellular developmental cycle in vivo. Clinical treatment of chlamydial
      infection is typically initiated upon occurrence of symptomatology and is
      directed against an asynchronous population of different chlamydial developmental
      forms. Pharmacodynamics of antichlamydial drugs are predominantly characterized
      by MICs; however, in vitro determinations of MIC may not reflect differential
      susceptibilities of the developmental cycle. In this study, we correlated the
      antichlamydial effect of erythromycin, rifampin, doxycycline, and ciprofloxacin
      with the developmental stage of a fast-replicating and a slow-replicating
      chlamydial species. In addition, we describe the influence of concentration on
      killing. Extracellular elementary bodies and very-early-phase and late-phase
      chlamydiae were refractory to all tested antibiotics except rifampin, which was
      very effective against early-cycle chlamydiae. Rifampin was the most effective
      antibiotic overall, killed in a dose dependent matter, and exhibited moderate
      synergism with erythromycin. These considerations provide important information
      on chlamydial biology and antimicrobial susceptibility. A combinational therapy
      of rifampin and a macrolide should be considered in therapy-refractory
      infections.

PMID- 15855507
TI  - Multidrug resistance in Staphylococcus aureus due to overexpression of a novel
      multidrug and toxin extrusion (MATE) transport protein.
AB  - Efflux is an important mechanism of multidrug resistance (MDR) in bacteria. The
      multidrug and toxin extrusion (MATE) family is the most recently described group
      of MDR efflux proteins, none of which have previously been identified in
      Staphylococcus aureus. Two independently derived S. aureus mutants having efflux
      related MDR phenotypes were studied using microarray technology and a marked
      overexpression of an open reading frame (ORF; mepA) encoding a protein homologous
      with MATE family proteins was observed in both. There was concomitant
      overexpression of ORFs in close proximity to mepA (approximately 100 bp) encoding
      a MarR-type regulator (mepR, upstream of mepA) and a protein of unknown function
      (mepB, downstream). Experiments in which mepA was overexpressed or disrupted
      revealed that the encoded protein has a broad substrate profile that includes
      several monovalent and divalent biocides and the fluoroquinolone antimicrobial
      agents norfloxacin and ciprofloxacin. The function of MepB is obscure, it does
      not contribute to the MDR phenotype conferred by MepA. MepR overexpression
      reversed the MDR phenotypes of both mutants by repressing mepA transcription. All
      three ORFs are preferentially transcribed as a single mepRAB unit, suggesting
      that the three genes form an operon.

PMID- 15855508
TI  - A novel MATE family efflux pump contributes to the reduced susceptibility of
      laboratory-derived Staphylococcus aureus mutants to tigecycline.
AB  - Tigecycline, an expanded-broad-spectrum glycylcycline antibiotic is not affected
      by the classical tetracycline resistance determinants found in Staphylococcus
      aureus. The in vitro selection of mutants with reduced susceptibility to
      tigecycline was evaluated for two methicillin-resistant S. aureus strains by
      serial passage in increasing concentrations of tigecycline. Both strains showed a
      stepwise elevation in tigecycline MIC over a period of 16 days, resulting in an
      increase in tigecycline MIC of 16- and 32-fold for N315 and Mu3, respectively.
      Transcriptional profiling revealed that both mutants exhibited over 100-fold
      increased expression of a gene cluster, mepRAB (multidrug export protein),
      encoding a MarR-like transcriptional regulator (mepR), a novel MATE family efflux
      pump (mepA), and a hypothetical protein of unknown function (mepB). Sequencing of
      the mepR gene in the mutant strains identified changes that presumably
      inactivated the MepR protein, which suggested that MepR functions as a repressor
      of mepA. Overexpression of mepA in a wild-type background caused a decrease in
      susceptibility to tigecycline and other substrates for MATE-type efflux pumps,
      although it was not sufficient to confer high-level resistance to tigecycline.
      Complementation of the mepR defect by overexpressing a wild-type mepR gene
      reduced mepA transcription and lowered the tigecycline MIC in the mutants.
      Transcription of tet(M) also increased by over 40-fold in the Mu3 mutant. This
      was attributed to a deletion in the promoter region of the gene that removed a
      stem-loop responsible for transcriptional attenuation. However, overexpression of
      the tet(M) transcript in a tigecycline-susceptible strain was not enough to
      significantly increase the MIC of tigecycline. These results suggest that the
      overexpression of mepA but not tet(M) may contribute to decreased susceptibility
      of tigecycline in S. aureus.

PMID- 15855509
TI  - Evolution of TEM-type extended-spectrum beta-lactamases in clinical
      Enterobacteriaceae strains in Poland.
AB  - Seventeen extended-spectrum beta-lactamase (ESBL)-producing isolates of the
      family Enterobacteriaceae recovered from 1998 to 2000 in hospitals of five
      different cities in Poland were analyzed. They expressed several TEM-type ESBLs,
      TEM-4, TEM-29, TEM-85, TEM-86, TEM-93, and TEM-94. TEM-85 (L21F, R164S, E240K,
      T265M), TEM-86 (L21F, R164S, A237T, E240K, T265M), TEM-93 (M182T, G238S, E240K),
      and TEM-94 (L21F, E104K, M182T, G238S, T265M) were identified for the first time.
      Including the enzymes described earlier, TEM-47, TEM-48, TEM-49, and TEM-68, the
      group of known ESBLs of the TEM family produced by enterobacteria in Polish
      hospitals has increased to 10 variants. Comparative sequence analysis of the
      genes coding for all these beta-lactamases revealed a view of their possible
      evolution, which, apart from the gradual acquisition of various mutations, could
      also have involved recombination events. Two different bla(TEM-1) gene alleles
      were precursors of the ESBL genes: bla(TEM-1A), which was the ancestor of bla(TEM
      93), and bla(TEM-1F), from which all the remaining genes originated. The
      evolution of the bla(TEM-1F)-related genes most probably consisted of three major
      separate lineages, one of which, including bla(TEM-4), bla(TEM-47), bla(TEM-48),
      bla(TEM-49), bla(TEM-68), and bla(TEM-94), was highly structured itself and could
      have been initiated by the bla(TEM-25) gene, identified exclusively in France so
      far. Plasmid fingerprinting analysis revealed a high degree of diversity of
      plasmids carrying related bla(TEM) genes, which suggested either the intense
      diversification or transposition of bla(TEM) genes between different plasmids or
      some contribution of convergent evolution. The results of this study clearly
      demonstrate that the environment of Polish hospitals has been highly favorable
      for the rapid evolution of ESBLs.

PMID- 15855510
TI  - Evaluation by monte carlo simulation of the pharmacokinetics of two doses of
      meropenem administered intermittently or as a continuous infusion in healthy
      volunteers.
AB  - Meropenem is a broad-spectrum carbapenem antibacterial agent. In order to
      optimize levels in plasma relative to the MICs, the ideal dose level and dosage
      regimen need to be determined. The pharmacokinetics of meropenem were studied in
      two groups, each comprising eight healthy volunteers who received the following
      doses: 500 mg as an intravenous infusion over 30 min three times a day (t.i.d.)
      versus a 250-mg loading dose followed by a 1,500 mg continuous infusion over 24 h
      for group A and 1,000 mg as an intravenous infusion over 30 min t.i.d. versus a
      500-mg loading dose followed by a 3,000-mg continuous infusion over 24 h for
      group B. Meropenem concentrations in plasma and urine were determined by liquid
      chromatography-mass spectrometry/mass spectrometry and high-performance liquid
      chromatography with UV detection, respectively. Pharmacokinetic calculations were
      done by use of a two-compartment open model, and the data were extrapolated by
      Monte Carlo simulations for 10,000 simulated subjects for pharmacodynamic
      evaluation. There were no significant differences in total clearance and renal
      clearance between group A and group B or between the intermittent treatment and
      the continuous infusion. The analyses of the probability of target attainment by
      MIC for the high- and low-dose continuous infusions were robust up to MICs of 4
      mg/liter and 2 mg/liter, respectively. The corresponding values for intermittent
      infusions were only 0.5 mg/liter and 0.25 mg/liter. When these observations were
      correlated with MICs obtained from the MYSTIC database, intermittent infusion
      results in adequate activity against two of the most common nosocomially acquired
      pathogens, Klebsiella pneumoniae and Enterobacter cloacae. However, against
      Pseudomonas aeruginosa, the evaluation shows a clear advantage of high-dose
      therapy administered as a continuous infusion. We believe that in the empirical
      therapy situation, the continuous-infusion mode of administration is most worth
      the extra efforts. We conclude that clinical trials for evaluation of the
      continuous infusions of meropenem in critically ill patients are warranted.

PMID- 15855511
TI  - Mechanism of action of a novel series of naphthyridine-type ribosome inhibitors:
      enhancement of tRNA footprinting at the decoding site of 16S rRNA.
AB  - The novel ribosome inhibitors (NRIs) are a broad-spectrum naphthyridine class
      that selectively inhibits bacterial protein synthesis (P. J. Dandliker et al.,
      Antimicrob. Agents Chemother. 47:3831-3839, 2003). Footprinting experiments,
      using a range of NRIs and chemical modification agents on Escherichia coli
      ribosomes, revealed no evidence for direct protection of rRNA. In the presence of
      tRNA, however, we found that NRIs enhanced the known ribosomal footprinting
      pattern of tRNA in a dose-dependent manner. The most prominent increase in
      protection, at A1492/3 and A1413 in helix-44 of 16S RNA, strictly required the
      presence of tRNA and poly(U), and the effect was correlated with the potency of
      the inhibitor. Radioligand binding studies with inhibitor [(3)H]A-424902 showed
      that the compound binds to tRNA, either in its charged or uncharged form. The
      dissociation constant for [(3)H]A-424902 binding to Phe-tRNA(Phe) was determined
      to be 1.8 microM, near its translation inhibition potency of 1.6 muM in a cell
      free S. pneumoniae extract assay. The compound did not change the binding of
      radiolabeled tRNA to the 30S ribosomal subunit. Taken together, these results
      imply that the NRIs exert their effects on protein synthesis by structurally
      perturbing the tRNA/30S complex at the decoding site.

PMID- 15855512
TI  - Selective intracellular activation of a novel prodrug of the human
      immunodeficiency virus reverse transcriptase inhibitor tenofovir leads to
      preferential distribution and accumulation in lymphatic tissue.
AB  - An isopropylalaninyl monoamidate phenyl monoester prodrug of tenofovir (GS 7340)
      was prepared, and its in vitro antiviral activity, metabolism, and
      pharmacokinetics in dogs were determined. The 50% effective concentration
      (EC(50)) of GS 7340 against human immunodeficiency virus type 1 in MT-2 cells was
      0.005 microM compared to an EC(50) of 5 microM for the parent drug, tenofovir.
      The (L)-alaninyl analog (GS 7340) was >1,000-fold more active than the (D)
      alaninyl analog. GS 7340 has a half-life of 90 min in human plasma at 37 degrees
      C and a half-life of 28.3 min in an MT-2 cell extract at 37 degrees C. The
      antiviral activity (>10 x the EC(50)) and the metabolic stability in MT-2 cell
      extracts (>35 x) and plasma (>2.5 x) were also sensitive to the stereochemistry
      at the phosphorus. After a single oral dose of GS 7340 (10 mg-eq/kg tenofovir) to
      male beagle dogs, the plasma bioavailability of tenofovir compared to an
      intravenous dose of tenofovir was 17%. The total intracellular concentration of
      all tenofovir species in isolated peripheral blood mononuclear cells at 24 h was
      63 microg-eq/ml compared to 0.2 microg-eq/ml in plasma. A radiolabeled
      distribution study with dogs resulted in an increased distribution of tenofovir
      to tissues of lymphatic origin compared to the commercially available prodrug
      tenofovir DF (Viread).

PMID- 15855513
TI  - Measurement of intracellular didanosine and tenofovir phosphorylated metabolites
      and possible interaction of the two drugs in human immunodeficiency virus
      infected patients.
AB  - Recent work has demonstrated the existence of a systemic interaction between
      didanosine (ddI) and tenofovir disoproxyl fumarate (TDF) that leads to a
      significant increase in plasma ddI levels when coadministered with TDF (40 to 50%
      increase). These two drugs are, respectively, nucleoside and nucleotide analogues
      of adenosine and efficiently inhibit the human immunodeficiency virus (HIV)
      reverse transcriptase when transformed to their triphosphate moieties in the
      intracellular (IC) medium (ddA-TP and TFV-DP, respectively). Since ddI and TDF
      partly share the same IC metabolic pathway leading to the active triphosphates,
      we investigated a putative IC interaction. We used high-performance liquid
      chromatography-tandem mass spectrometry techniques to determine ddA-TP and TFV-DP
      IC levels in HIV-infected patients cotreated with both drugs, in comparison with
      patients treated with just one of the two drugs. These measurements revealed no
      significant differences in IC levels of the corresponding triphosphates when ddI
      (250 mg, once a day [QD]) was coadministered with TDF (300 mg, QD) compared to
      ddI 400 mg (QD) administered without TDF, thus supporting the dose adaptation
      proposed for this combination. However, we observed that both ddA-TP and TFV-DP
      have very long IC half-lives, resulting in unusual IC pharmacokinetic profiles
      with no significant changes in triphosphate concentrations between two dosings.
      In the case of TFV-DP, this t(1/2) of elimination was roughly estimated to be 180
      h (7.5 days). This characteristic is certainly interesting in terms of efficacy
      but could have some drawbacks in terms of virus resistance for patients
      discontinuing these drugs.

PMID- 15855515
TI  - Plasmid-encoded Tet B tetracycline resistance in Haemophilus parasuis.
AB  - The complete sequence of two plasmids, pHS-Tet (5.1 kb) and pHS-Rec (9.5 kb),
      isolated from Haemophilus parasuis strain HS1543 has been obtained. Plasmid pHS
      Tet contains four open reading frames including a tet(B) tetracycline resistance
      gene which unusually did not have an associated tetR repressor gene. From a total
      of 45 H. parasuis isolates surveyed (15 international reference strains, 15 field
      isolates selected for their genetic diversity, and 15 recent Australian field
      isolates), 2 tetracycline-resistant field isolates (HS226 and HS1859) were
      identified. Analysis of three additional isolates from the same disease outbreak
      as strain HS1859 revealed a further tetracycline-resistant H. parasuis strain
      (HS1857, serovar 8) and a tetracycline-resistant Actinobacillus pleuropneumoniae
      strain (HS1861). An approximately 10.6-kb plasmid was identified in field isolate
      HS226 and outbreak strains HS1857, HS1859, and HS1861. Southern hybridization
      analysis of these plasmids showed that the Tet B determinant was present, and
      restriction digest comparisons suggest that these plasmids are related. This is
      believed to be the first report of native H. parasuis plasmids and Tet B-mediated
      tetracycline resistance in this microorganism.

PMID- 15855514
TI  - Global transcriptional response of Bacillus subtilis to treatment with
      subinhibitory concentrations of antibiotics that inhibit protein synthesis.
AB  - Global gene expression patterns of Bacillus subtilis in response to subinhibitory
      concentrations of protein synthesis inhibitors (chloramphenicol, erythromycin,
      and gentamicin) were studied by DNA microarray analysis. B. subtilis cultures
      were treated with subinhibitory concentrations of protein synthesis inhibitors
      for 5, 15, 30, and 60 min, and transcriptional patterns were measured throughout
      the time course. Three major classes of genes were affected by the protein
      synthesis inhibitors: genes encoding transport/binding proteins, genes involved
      in protein synthesis, and genes involved in the metabolism of carbohydrates and
      related molecules. Similar expression patterns for a few classes of genes were
      observed due to treatment with chloramphenicol (0.4x MIC) or erythromycin (0.5x
      MIC), whereas expression patterns of gentamicin-treated cells were distinct.
      Expression of genes involved in metabolism of amino acids was altered by
      treatment with chloramphenicol and erythromycin but not by treatment with
      gentamicin. Heat shock genes were induced by gentamicin but repressed by
      chloramphenicol. Other genes induced by the protein synthesis inhibitors included
      the yheIH operon encoding ABC transporter-like proteins, with similarity to
      multidrug efflux proteins, and the ysbAB operon encoding homologs of LrgAB that
      function to inhibit cell wall cleavage (murein hydrolase activity) and convey
      penicillin tolerance in Staphylococcus aureus.

PMID- 15855516
TI  - Antipneumococcal activity of ceftobiprole, a novel broad-spectrum cephalosporin.
AB  - Ceftobiprole (previously known as BAL9141), an anti-methicillin-resistant
      Staphylococcus aureus cephalosporin, was very highly active against a panel of
      299 drug-susceptible and -resistant pneumococci, with MIC(50) and MIC(90) values
      (microg/ml) of 0.016 and 0.016 (penicillin susceptible), 0.06 and 0.5 (penicillin
      intermediate), and 0.5 and 1.0 (penicillin resistant). Ceftobiprole, imipenem,
      and ertapenem had lower MICs against all pneumococcal strains than amoxicillin,
      cefepime, ceftriaxone, cefotaxime, cefuroxime, or cefdinir. Macrolide and
      penicillin G MICs generally varied in parallel, whereas fluoroquinolone MICs did
      not correlate with penicillin or macrolide susceptibility or resistance. All
      strains were susceptible to linezolid, quinupristin-dalfopristin, daptomycin,
      vancomycin, and teicoplanin. Time-kill analyses showed that at 1x and 2x the MIC,
      ceftobiprole was bactericidal against 10/12 and 11/12 strains, respectively.
      Levofloxacin, moxifloxacin, vancomycin, and teicoplanin were each bactericidal
      against 10 to 12 strains at 2x the MIC. Azithromycin and clarithromycin were
      slowly bactericidal, and telithromycin was bactericidal against only 5/12 strains
      at 2x the MIC. Linezolid was mainly bacteriostatic, whereas quinupristin
      dalfopristin and daptomycin showed marked killing at early time periods.
      Prolonged serial passage in the presence of subinhibitory concentrations of
      ceftobiprole failed to yield mutants with high MICs towards this cephalosporin,
      and single-passage selection showed very low frequencies of spontaneous mutants
      with breakthrough MICs towards ceftobiprole.

PMID- 15855517
TI  - Pharmacodynamic activity of telithromycin at simulated clinically achievable free
      drug concentrations in serum and epithelial lining fluid against efflux (mefE)
      producing macrolide-resistant Streptococcus pneumoniae for which telithromycin
      MICs vary.
AB  - The present study, using an in vitro model, assessed telithromycin
      pharmacodynamic activity at simulated clinically achievable free-drug
      concentrations in serum (S) and epithelial lining fluid (ELF) against efflux
      (mefE)-producing macrolide-resistant Streptococcus pneumoniae. Two macrolide
      susceptible (PCR negative for both mefE and ermB) and 11 efflux-producing
      macrolide-resistant [PCR-positive for mefE and negative for ermB) S. pneumoniae
      strains with various telithromycin MICs (0.015 to 1 microg/ml) were tested. The
      steady-state pharmacokinetics of telithromycin were modeled, simulating a dosage
      of 800 mg orally once daily administered at time 0 and at 24 h (free-drug maximum
      concentration [C(max)] in serum, 0.7 microg/ml; half-life [t(1/2)], 10 h; free
      drug C(max) in ELF, 6.0 microg/ml; t(1/2), 10 h). Starting inocula were 10(6)
      CFU/ml in Mueller-Hinton Broth with 2% lysed horse blood. Sampling at 0, 2, 4, 6,
      12, 24, and 48 h assessed the extent of bacterial killing (decrease in log(10)
      CFU/ml versus initial inoculum). Free-telithromycin concentrations in serum
      achieved in the model were C(max) 0.9 +/- 0.08 microg/ml, area under the curve to
      MIC (AUC(0-24 h)) 6.4 +/- 1.5 microg . h/ml, and t(1/2) of 10.6 +/- 0.6 h.
      Telithromycin-free ELF concentrations achieved in the model were C(max) 6.6 +/-
      0.8 microg/ml, AUC(0-24 h) 45.5 +/- 5.5 microg . h/ml, and t(1/2) of 10.5 +/- 1.7
      h. Free-telithromycin S and ELF concentrations rapidly eradicated efflux
      producing macrolide-resistant S. pneumoniae with telithromycin MICs up to and
      including 0.25 microg/ml and 1 microg/ml, respectively. Free-telithromycin S and
      ELF concentrations simulating C(max)/MIC > or = 3.5 and AUC(0-24 h)/MIC > or = 25
      completely eradicated (> or =4 log(10) killing) macrolide-resistant S. pneumoniae
      at 24 and 48 h. Free-telithromycin concentrations in serum simulating C(max)/MIC
      > or = 1.8 and AUC(0-24 h)/MIC > or = 12.5 were bacteriostatic (0.1 to 0.2
      log(10) killing) against macrolide-resistant S. pneumoniae at 24 and 48 h. In
      conclusion, free-telithromycin concentrations in serum and ELF simulating
      C(max)/MIC > or = 3.5 and AUC(0-24 h)/MIC > or = 25 completely eradicated (> or
      =4 log(10) killing) macrolide-resistant S. pneumoniae at 24 and 48 h.

PMID- 15855518
TI  - Dual targeting of topoisomerase IV and gyrase to reduce mutant selection: direct
      testing of the paradigm by using WCK-1734, a new fluoroquinolone, and
      ciprofloxacin.
AB  - Quinolones that act equally against DNA gyrase and topoisomerase IV are a
      desirable modality to decrease the selection of resistant strains. We first
      determined by genetic and biochemical studies in Staphylococcus aureus that the
      primary target enzyme of WCK-1734, a new quinolone, was DNA gyrase. A single
      mutation in gyrase, but not topoisomerase IV, caused a two- to fourfold increase
      in the MIC. Studies with purified topoisomerase IV and gyrase from S. aureus also
      showed that gyrase was more sensitive than topoisomerase IV to WCK-1734 (50%
      inhibitory concentration, 1.25 and 2.5 to 5.0 microg/ml, respectively; 50%
      stimulation of cleavage complex formation, 0.62 and 2.5 to 5.0 microg/ml,
      respectively). To test the effect of balanced activity of quinolones against the
      two target enzymes, we measured the frequency of selection of mutants with
      ciprofloxacin (which targets topoisomerase IV) and WCK-1734 alone and in
      combination. With the combination of ciprofloxacin and WCK-1734, each at its MIC,
      the ratio of frequency of mutants selected was significantly lower than that with
      each drug alone at two times their respective MICs. We further characterized
      resistant strains selected with the combination of ciprofloxacin and WCK-1734 and
      found evidence to suggest the existence of novel mutational mechanisms for low
      level quinolone resistance. By use of a combination of differentially targeting
      quinolones, this study provides novel data in direct support of the paradigm for
      dual targeting of quinolone action and reduced development of resistance.

PMID- 15855519
TI  - Cloning and characterization of a chromosomal class C beta-lactamase and its
      regulatory gene in Laribacter hongkongensis.
AB  - Laribacter hongkongensis, a newly discovered bacterium recently shown to be
      associated with community-acquired gastroenteritis, is generally resistant to
      most beta-lactams except the carbapenems. We describe the cloning and
      characterization of a novel chromosomal class C beta-lactamase and its regulatory
      gene in L. hongkongensis. Two genes, ampC and ampR, were cloned by inserting
      restriction fragments of genomic DNA from L. hongkongensis strain HLHK5 into pBK
      CMV to give the recombinant plasmid pBK-LHK-5. The ampR and ampC genes and their
      promoters were divergently oriented, with the ampR gene immediately upstream of
      the ampC gene and an intercistronic Lys-R motif, typical of inducible ampC-ampR
      regulatory systems. The deduced amino acid sequence of the cloned AmpC beta
      lactamase (pI 8.1) contained consensus motifs characteristic of class C beta
      lactamases but had identities no greater than 46% to known class C beta
      lactamases. The kinetic properties of this AmpC were also compatible with those
      of a class C beta-lactamase. PCR of 20 clinical isolates of L. hongkongensis,
      including HLHK5, showed the presence of both ampC and ampR genes in all isolates.
      Southern hybridization suggested that the ampC gene of HLHK5 was chromosomally
      encoded. Subcloning experiments showed that the expression of the ampC gene of
      HLHK5 was regulated by its ampR gene, which acts as a repressor. The beta
      lactamase characterized from strain HLHK5 was named LHK-5 (gene, bla(LHK-5)) and
      represents the first example of AmpC beta-lactamase in the beta subdivision of
      proteobacteria.

PMID- 15855520
TI  - Geographical and ecological analysis of resistance, coresistance, and coupled
      resistance to antimicrobials in respiratory pathogenic bacteria in Spain.
AB  - A multicenter susceptibility surveillance (the S.A.U.C.E. project) including
      2,721 Streptococcus pneumoniae, 3,174 Streptococcus pyogenes, and 2,645
      Haemophilus influenzae consecutive isolates was carried out in 25 hospitals all
      over Spain from November 2001 to October 2002 to evaluate the current
      epidemiology of resistance of the main bacteria involved in community-acquired
      respiratory tract infections. Susceptibility testing was performed in a single
      centralized laboratory by a broth microdilution method. The prevalence of
      resistant S. pneumoniae strains was 0.4% for cefotaxime, 4.4% for amoxicillin and
      amoxicillin-clavulanic acid, 25.6% for cefuroxime-axetil, 34.5% for erythromycin,
      clarithromycin, and azithromycin, and 36.0% for cefaclor. Phenotypes of
      resistance to erythromycin were MLS(B) (macrolide-lincosamide-streptogramin B) in
      89.9% (gene ermB) and M (macrolide) in 9.7% of cases (gene mefA). No strain
      harbored both genes simultaneously. Serotypes 19, 6, 23, 14, and 3 were the most
      prevalent, accounting for 54.6% of the total isolates. Resistance to macrolides
      seems to be the most alarming point, since among penicillin-susceptible isolates
      it reached 15.1% compared to 55.8% among penicillin-resistant strains.
      Geographically, a number of regions had rates of erythromycin resistance above
      40% (even higher in children). Resistance to erythromycin was also high in S.
      pyogenes isolates: mean regional 33.2%, beta-lactamase-producing H. influenzae
      were 20%, whereas 4.4% had a beta-lactamase-negative, ampicillin-resistant
      phenotype. We highlight the importance of different geographical frequencies of
      coresistance (associations of resistance to different drugs within the same
      species) and coupled resistance (association of resistance between different
      species) probably resulting from different local coselective events.

PMID- 15855521
TI  - OXA-46, a new class D beta-lactamase of narrow substrate specificity encoded by a
      blaVIM-1-containing integron from a Pseudomonas aeruginosa clinical isolate.
AB  - A novel OXA-type enzyme, named OXA-46, was found to be encoded by a gene cassette
      inserted into a class 1 integron from a multidrug-resistant Pseudomonas
      aeruginosa clinical isolate. The variable region of the integron also contained a
      bla(VIM-1) metallo-beta-lactamase cassette and a duplicated aacA4 aminoglycoside
      acetyltransferase cassette. OXA-46 belongs to the OXA-2 lineage of class D beta
      lactamases. It exhibits 78% sequence identity with OXA-2 and the highest
      similarity (around 92% identity) with another OXA-type enzyme detected in
      clinical isolates of Burkholderia cepacia and in unidentified bacteria from a
      wastewater plant. Expression of bla(OXA-46) in Escherichia coli decreased
      susceptibility to penicillins and narrow-spectrum cephalosporins but not to
      extended-spectrum cephalosporins, cefsulodin, aztreonam, or carbapenems. The
      enzyme was overproduced in E. coli and purified by two anion-exchange
      chromatography steps (approximate yield, 6 mg/liter). OXA-46 was made of a 28.5
      kDa polypeptide and exhibited an alkaline pI (7.8). In its native form OXA-46
      appeared to be dimeric, and the oligomerization state was not affected by EDTA.
      Kinetic analysis of OXA-46 revealed a specificity for narrow-spectrum substrates,
      including oxacillin, other penicillins (but not temocillin), and narrow-spectrum
      cephalosporins. The enzyme apparently did not interact with temocillin, oxyimino
      cephalosporins, or aztreonam. OXA-46 was inactivated by tazobactam and
      carbapenems and, although less efficiently, also by clavulanic acid. Enzyme
      activity was not affected either by EDTA or by divalent cations and exhibited low
      susceptibility to NaCl. These findings underscore the functional and structural
      diversity that can be encountered among class D beta-lactamases.

PMID- 15855522
TI  - Benznidazole therapy in Trypanosoma cruzi-infected mice blocks thymic involution
      and apoptosis of CD4+CD8+ double-positive thymocytes.
AB  - Several alterations involving peripheral lymphoid organs have been extensively
      described after experimental Trypanosoma cruzi infection. Thymic involution
      occurs as well in infected mice, with both structural and functional alterations
      in the organ. Despite these abnormalities, specific immune response proceeds to
      control parasitemia and the participation of T lymphocytes is essential. However,
      there are relatively few studies on the impact of benznidazole (N-benzyl-2
      nitroimidazole acetamide) upon this response. In this present work, we decided to
      evaluate the impact of benznidazole treatment upon the thymus involution
      following acute T. cruzi infection in mice. We have provided evidence that
      benznidazole treatment controls the severe abnormalities seen in the thymus due
      to T. cruzi infection. The thymocyte loss related to the depletion of double
      positive CD4(+)CD8(+) thymocytes was clearly prevented, corroborating the idea
      that the mechanism responsible for the prevention of thymus involution is related
      to the decrease of apoptosis rate in this subset after benznidazole treatment.
      Furthermore, we demonstrated the prevention of enhanced extracellular matrix
      deposition in the thymus. In conclusion, the preservation of thymus homeostasis,
      even though partial, was accomplished after benznidazole treatment. Our data are
      consistent with the notion that different outcomes of T. cruzi infection may be
      linked to differences in the parasite load concomitant to fine tuning of the host
      immune response.

PMID- 15855523
TI  - Role of the ABC transporter MRPA (PGPA) in antimony resistance in Leishmania
      infantum axenic and intracellular amastigotes.
AB  - Antimonial compounds are the mainstay for the treatment of infections with the
      protozoan parasite Leishmania. We present our studies on Leishmania infantum
      amastigote parasites selected for resistance to potassium antimonyl tartrate
      [Sb(III)]. Inside macrophages, the Sb(III)-selected cells are cross-resistant to
      sodium stibogluconate (Pentostam), the main drug used against Leishmania.
      Putative alterations in the level of expression of more than 40 genes were
      compared between susceptible and resistant axenic amastigotes using customized
      DNA microarrays. The expression of three genes coding for the ABC transporter
      MRPA (PGPA), S-adenosylhomocysteine hydrolase, and folylpolyglutamate synthase
      was found to be consistently increased. The levels of cysteine were found to be
      increased in the mutant. Transfection of the MRPA gene was shown to confer sodium
      stibogluconate resistance in intracellular parasites. This MRPA-mediated
      resistance could be reverted by using the glutathione biosynthesis-specific
      inhibitor buthionine sulfoximine. These results highlight for the first time the
      role of MRPA in antimony resistance in the amastigote stage of the parasite and
      suggest a strategy for reversing resistance.

PMID- 15855524
TI  - Mechanism of anti-human immunodeficiency virus activity of beta-D-6
      cyclopropylamino-2',3'-didehydro-2',3'-dideoxyguanosine.
AB  - To better understand the importance of the oxygen in the ribose ring of planar
      unsaturated nucleoside analogs that target human immunodeficiency virus (HIV), a
      6-cyclopropyl-substituted prodrug of 2',3'-didehydro-2',3'-dideoxyguanosine
      (cyclo-d4G) was synthesized, and its cellular metabolism, antiviral activity, and
      pharmacokinetic behavior were studied. Cyclo-d4G had selective anti-HIV activity
      in primary blood mononuclear cells (PBMCs), effectively inhibiting the LAI strain
      of HIV-1 by 50% at 1.1 +/- 0.1 microM while showing 50% inhibition of cell
      viability at 84.5 microM. The antiviral activity in PBMCs was not markedly
      affected by mutations of methionine to valine at position 184 or by thymidine
      associated mutations in the viral reverse transcriptase. Mutations of leucine 74
      to valine and of lysine 65 to arginine had mild to moderate resistance (as high
      as fivefold). Studies to delineate the mechanism of cellular metabolism and
      activation of cyclo-d4G showed reduced potency in inhibiting viral replication in
      the presence of the adenosine/adenylate deaminase inhibitor 2'-deoxycoformycin,
      implying that the antiviral activity is due to its metabolism to the 2'-dGTP
      analog d4GTP. Intracellular formation of sugar catabolites illustrates the
      chemical and potentially enzymatic instability of the glycosidic linkage in d4G.
      Further studies suggest that cyclo-d4G has a novel intracellular phosphorylation
      pathway. Cyclo-d4G had a lower potential to cause mitochondrial toxicity than
      2',3'-dideoxycytidine and 2',3'-didehydro-3'-deoxythymidine in neuronal cells.
      Also, cyclo-d4G had advantageous synergism with many currently used anti-HIV
      drugs. Poor oral bioavailability observed in rhesus monkeys may be due to the
      labile glycosidic bond, and special formulation may be necessary for oral
      delivery.

PMID- 15855525
TI  - Altered PBP 2A and its role in the development of penicillin, cefotaxime, and
      ceftriaxone resistance in a clinical isolate of Streptococcus pneumoniae.
AB  - We report the unusual involvement of altered PBP 2A in the development of beta
      lactam resistance in Streptococcus pneumoniae. This was investigated amid three
      identical serotype 14 isolates (designated isolates 1, 2, and 3, respectively) of
      pneumococci cultured successfully from the blood of a human immunodeficiency
      virus-seropositive child with recurrent pneumonia. The passage of this strain
      through its human host induced several changes in the bacterium, which is typical
      of the adaptive and evolving nature of the pneumococcus. An efflux resistance
      mechanism, which conferred increased ciprofloxacin resistance, was induced in
      isolates 2 and 3. In addition, faster growth rates and larger capsules were also
      observed for these isolates, with respect to isolate 1. Notably, compared to
      isolates 1 and 2, isolate 3 showed a decrease in penicillin, cefotaxime, and
      ceftriaxone resistance. This change was associated with the replacement of an
      altered PBP 2A for an unaltered PBP 2A. In all likelihood, these events produced
      a strain which evolved into a fitter and more virulent type, isolate 3, that
      resulted in an aggravated pneumococcal infection and ultimately in the patient's
      death.

PMID- 15855526
TI  - Lethality of quinolones against Mycobacterium smegmatis in the presence or
      absence of chloramphenicol.
AB  - Quinolones were examined for rapid lethal activity against Mycobacterium
      smegmatis in the presence and absence of chloramphenicol, an inhibitor of protein
      synthesis. C-8 methoxy, C-6 fluorine, and particular C-7 ring substituents
      enhanced rapid killing. With the surprising exception of moxifloxacin, higher
      quinolone concentrations were required for lethal activity in the presence of
      chloramphenicol than in its absence. Moxifloxacin was also unusual in lacking the
      time lag characteristic of fluoroquinolone lethality. Several fluoroquinolone
      dimers, which represent quinolones with large C-7 substituents, showed modest
      bacteriostatic activity. Unlike other quinolones, the dimers failed to display
      lethal activity. The insensitivity of moxifloxacin to chloramphenicol has not
      been observed with other bacteria and may therefore reflect unique aspects of
      mycobacterial gyrase.

PMID- 15855527
TI  - Novel human immunodeficiency virus type 1 protease mutations potentially involved
      in resistance to protease inhibitors.
AB  - Plasma-derived sequences of human immunodeficiency virus type 1 (HIV-1) protease
      from 1,162 patients (457 drug-naive patients and 705 patients receiving protease
      inhibitor [PI]-containing antiretroviral regimens) led to the identification and
      characterization of 17 novel protease mutations potentially associated with
      resistance to PIs. Fourteen mutations were positively associated with PIs and
      significantly correlated in pairs and/or clusters with known PI resistance
      mutations, suggesting their contribution to PI resistance. In particular, E34Q,
      K43T, and K55R, which were associated with lopinavir treatment, correlated with
      mutations associated with lopinavir resistance (E34Q with either L33F or F53L, or
      K43T with I54A) or clustered with multi-PI resistance mutations (K43T with V82A
      and I54V or V82A, V32I, and I47V, or K55R with V82A, I54V, and M46I). On the
      other hand, C95F, which was associated with treatment with saquinavir and
      indinavir, was highly expressed in clusters with either L90M and I93L or V82A and
      G48V. K45R and K20T, which were associated with nelfinavir treatment, were
      specifically associated with D30N and N88D and with L90M, respectively.
      Structural analysis showed that several correlated positions were within 8 A of
      each other, confirming the role of the local environment for interactions among
      mutations. We also identified three protease mutations (T12A, L63Q, and H69N)
      whose frequencies significantly decreased in PI-treated patients compared with
      that in drug-naive patients. They never showed positive correlations with PI
      resistance mutations; if anything, H69N showed a negative correlation with the
      compensatory mutations M36I and L10I. These mutations may prevent the appearance
      of PI resistance mutations, thus increasing the genetic barrier to PI resistance.
      Overall, our study contributes to a better definition of protease mutational
      patterns that regulate PI resistance and strongly suggests that other (novel)
      mutations beyond those currently known to confer resistance should be taken into
      account to better predict resistance to antiretroviral drugs.

PMID- 15855528
TI  - Mechanistic study of the photodynamic inactivation of Candida albicans by a
      cationic porphyrin.
AB  - The growing resistance against antifungal agents has renewed the search for
      alternative treatment modalities, and antimicrobial photodynamic inactivation
      (PDI) is a potential candidate. The cationic porphyrin 5-phenyl-10,15,20-Tris(N
      methyl-4-pyridyl)porphyrin chloride (TriP[4]) is a photosensitizer that in
      combination with light can inactivate bacteria, fungi, and viruses. For future
      improvement of the efficacy of PDI of clinically relevant fungi such as Candida
      albicans, we sought to understand the working mechanism by following the response
      of C. albicans exposed to PDI using fluorescence confocal microscopy and freeze
      fracture electron microscopy. The following events were observed under dark
      conditions: TriP[4] binds to the cell envelope of C. albicans, and none or very
      little TriP[4] enters the cell. Upon illumination the cell membrane is damaged
      and eventually becomes permeable for TriP[4]. After lethal membrane damage, a
      massive influx of TriP[4] into the cell occurs. Only the vacuole membrane is
      resistant to PDI-induced damage once TriP[4] passes the plasma membrane.
      Increasing the incubation time of C. albicans with TriP[4] prior to illumination
      did not increase the influx of TriP[4] into the cell or the efficacy of PDI.
      After the replacement of 100% phosphate-buffered saline (PBS) by 10% PBS as the
      medium, C. albicans became permeable for TriP[4] during dark incubation and the
      efficacy of PDI increased dramatically. In conclusion, C. albicans can be
      successfully inactivated by the cationic porphyrin TriP[4], and the cytoplasmic
      membrane is the target organelle. TriP[4] influx occurred only after cell death.

PMID- 15855529
TI  - Targeting Tn5 transposase identifies human immunodeficiency virus type 1
      inhibitors.
AB  - Human immunodeficiency virus (HIV) type 1 (HIV-1) integrase is an underutilized
      drug target for the treatment of HIV infection. One limiting factor is the lack
      of costructural data for use in the rational design or modification of integrase
      inhibitors. Tn5 transposase is a structurally well characterized, related protein
      that may serve as a useful surrogate. However, little data exist on inhibitor
      cross-reactivity. Here we screened 16,000 compounds using Tn5 transposase as the
      target and identified 20 compounds that appear to specifically inhibit complex
      assembly. Six were found to also inhibit HIV-1 integrase. These compounds likely
      interact with a highly conserved region presumably within the catalytic core.
      Most promising, several cinnamoyl derivatives were found to inhibit HIV
      transduction in cells. The identification of integrase inhibitors from a screen
      using Tn5 transposase as the target illustrates the utility of Tn5 as a surrogate
      for HIV-1 integration even though the relationship between the two systems is
      limited to the active site architecture and catalytic mechanism.

PMID- 15855530
TI  - Behavior of thymidylate kinase toward monophosphate metabolites and its role in
      the metabolism of 1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5-methyluracil
      (Clevudine) and 2',3'-didehydro-2',3'-dideoxythymidine in cells.
AB  - L-nucleoside analogs are a new class of antiviral and anticancer agents, several
      of which are currently used in the clinic. The phosphorylation of these agents to
      the triphosphate form is thought to be important for exertion of their
      pharmacological activities. 1-(2'-deoxy-2'-fluoro-beta-L-arabinofuranosyl)-5
      methyluracil (L-FMAU; Clevudine) is a thymidine analog that is currently under
      phase III clinical trials as an anti-human hepatitis B virus agent. We examined
      the behavior of its monophosphate metabolite with human recombinant thymidylate
      kinase (TMPK) and showed that L-FMAU monophosphate (L-FMAUMP) is a poorer
      substrate than its D-configuration anomer (D-FMAUMP). The phosphorylation
      efficiency of l-FMAUMP is similar to that of the monophosphate of 2',3'-didehydro
      2',3'-dideoxythymidine (d4T), an anti-human immunodeficiency virus analog, both
      of which are approximately 1% TMP. To clarify the role of human TMPK in the
      phosphorylation of L-FMAUMP to the diphosphate metabolite in cells, a Tet-On
      inducible human TMPK cell line system was established. In this system, the
      expression of TMPK is closely regulated in response to various concentrations of
      doxycycline. When the cells were treated with L-FMAU or d4T, the amounts of the
      diphosphate and triphosphate metabolites of these analogs were increased, in
      accordance with an increase in human TMPK activity in cells. In conclusion, this
      is the first demonstration of the behavior of TMPK toward L-FMAUMP. This study
      indicates that human TMPK can phosphorylate L-FMAUMP and play a critical role in
      L-FMAU metabolism in cells.

PMID- 15855531
TI  - Inhibitory effect of 2'-substituted nucleosides on hepatitis C virus replication
      correlates with metabolic properties in replicon cells.
AB  - Nucleosides have been widely used in the treatment of viral diseases, but
      relatively few have been identified as inhibitors of hepatitis C virus (HCV). The
      modified ribonucleosides, 2'-C-methyl-adenosine and 2'-O-methyl-cytidine, are
      potent inhibitors of HCV replication which specifically target the NS5B
      polymerase. Herein, a more extensive characterization of the effect of these
      compounds upon HCV replication in subgenomic replicons is reported. A highly
      selective antireplicative effect induced by the nucleosides in replicon
      containing cell lines was maintained during an exponential growth period with
      potencies which paralleled the reduction of both positive- and negative-strand
      RNA replication. Moreover, the inhibitory effect closely correlated with the
      intrinsic metabolic properties of differing replicon clonal lines. Interestingly,
      while 2'-C-methyl-adenosine elicited similar inhibitory potencies in different
      cell lines, 2'-O-methyl-cytidine was found to be inactive in one replicon cell
      line tested, although the corresponding triphosphates comparably inhibited the in
      vitro activity of replication complexes isolated from these cells and the
      activity of NS5B polymerase using synthetic templates. The lack of
      antireplicative effect, attributed to poor intracellular conversion of the 2'-O
      methyl-cytidine nucleoside to the active 5'-triphosphate, was reversed using a
      monophosphate prodrug. Thus, although replicon cells are useful for evaluating
      the effect of inhibitors upon HCV replication, these findings have important
      implications for their use in the identification and characterization of
      nucleosides and other chemotherapeutic agents requiring cellular metabolism.

PMID- 15855532
TI  - Replication fitness and NS5B drug sensitivity of diverse hepatitis C virus
      isolates characterized by using a transient replication assay.
AB  - The innate genetic variability characteristic of chronic hepatitis C virus (HCV)
      infection makes drug resistance a concern in the clinical development of HCV
      inhibitors. To address this, a transient replication assay was developed to
      evaluate the replication fitness and the drug sensitivity of NS5B sequences
      isolated from the sera of patients with chronic HCV infection. This novel assay
      directly compares replication between NS5B isolates, thus bypassing the potential
      sequence and metabolic differences which may arise with independent replicon cell
      lines. Patient-derived NS5B sequences were similar to those of the established
      HCV genotypes, but isolates from each patient shared genetic variability specific
      to that patient, with additional genetic variability observed across the
      individual isolates. Every sample provided functional NS5B isolates which
      supported subgenomic replication, frequently to levels comparable to that of
      laboratory-optimized replicons. All isolates were equivalently sensitive to an
      active-site nucleoside inhibitor, but the sensitivities to a panel of
      nonnucleoside inhibitors which targeted three distinct sites on NS5B varied among
      the isolates. In con1, the original laboratory-optimized replicon, the NS5B S282T
      substitution confers resistance to the nucleoside inhibitor but impairs
      replication. This substitution was engineered into both genotype 1a and genotype
      1b isolates. Replication was severely debilitated, demonstrating that no
      compensatory residues were encoded within these genetically diverse sequences to
      increase the replication fitness of the mutated replicons. This work describes a
      transient replicon-based assay that can support the clinical development of
      compounds which target NS5B and demonstrates its utility by examining several
      patient-derived NS5B isolates for replication fitness and differential
      sensitivity to NS5B inhibitors.

PMID- 15855533
TI  - Seven novel variants of the staphylococcal chromosomal cassette mec in
      methicillin-resistant Staphylococcus aureus isolates from Ireland.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered in Irish
      hospitals between 1971 and 2002 were characterized using multilocus sequence
      typing (MLST) (n = 130) and SCCmec typing (n = 172). Where atypical SCCmec typing
      results were obtained, PCR amplification of entire SCCmec elements, analysis of
      amplimer mobility, and nucleotide sequencing were undertaken. MLST revealed that
      129/130 isolates had the same genotypes as internationally spread MRSA clones,
      including ST239, ST247, ST250, ST5, ST22, ST36, and ST8. A novel genotype, ST496,
      was identified in one isolate. Half of the isolates (86/172) had SCCmec type I,
      IA, II, III, or IV. The remaining 86 isolates harbored novel SCCmec variants in
      three distinct genetic backgrounds: (i) 74/86 had genotype ST8 and either one of
      five novel SCCmec II (IIA, IIB, IIC, IID, and IIE) or one of two novel SCCmec IV
      (IVE and IVF) variants; (ii) 3/86 had genotype ST239 and a novel SCCmec III
      variant; (iii) 9/86 had a novel SCCmec I variant associated with ST250. SCCmec
      IVE and IVF were similar to SCCmec IVc and IVb, respectively, but differed in the
      region downstream of mecA. The five SCCmec II variants were similar to SCCmec IVb
      in the region upstream of the ccr complex but otherwise were similar to SCCmec
      II, except for the following regions: SCCmec IIA and IID had a novel mec complex,
      A.4 (Delta mecI-IS1182-Delta mecI-mecR1-mecA-IS431mec); SCCmec IIC and IIE had a
      novel mec complex, A.3 (IS1182-Delta mecI-mecR1-mecA-IS431mec); SCCmec IID and
      IIE lacked pUB110; SCCmec IIC and IIE lacked a region of DNA between Tn554 and
      the mec complex; and SCCmec IIB lacked Tn554. This study has demonstrated a
      hitherto-undescribed degree of diversity within SCCmec.

PMID- 15855534
TI  - Efficacy, plasma pharmacokinetics, and safety of icofungipen, an inhibitor of
      Candida isoleucyl-tRNA synthetase, in treatment of experimental disseminated
      candidiasis in persistently neutropenic rabbits.
AB  - Icofungipen (formerly PLD-118) is a synthetic derivative of the naturally
      occurring beta-amino acid cispentacin that blocks isoleucyl-tRNA synthetase,
      resulting in the inhibition of protein synthesis and growth of fungal cells. We
      investigated the efficacy, plasma pharmacokinetics, and safety of icofungipen in
      escalating dosages for the treatment of experimental subacute disseminated
      candidiasis in persistently neutropenic rabbits. Icofungipen was administered for
      10 days starting 24 h after the intravenous inoculation of 10(3) Candida albicans
      blastoconidia. Study groups consisted of rabbits treated with icofungipen at 4
      (ICO-4), 10 (ICO-10), and 25 (ICO-25) mg/kg of body weight/day in two divided
      dosages, rabbits treated with fluconazole at 10 mg/kg/day, rabbits treated with
      amphotericin B at 1 mg/kg/day, and untreated controls. Levels of icofungipen in
      plasma were derivatized by phthaldialdehyde and quantified by high-performance
      liquid chromatography with fluorescence detection. Rabbits treated with ICO-10 (P
      < 0.01) and ICO-25 (P < 0.001) showed significant dosage-dependent tissue
      clearance of C. albicans from the liver, spleen, kidney, brain, vitreous, vena
      cava, and lung in comparison to untreated controls. ICO-25 cleared C. albicans
      from all tissues and had activity comparable to that of amphotericin B versus
      untreated controls (P < 0.001). Pharmacokinetics of icofungipen in plasma
      approximated a dose-dependent relationship of the maximum concentration of drug
      in serum and the area under the concentration-time curve. There was no
      significant elevation of the levels of hepatic transaminases, alkaline
      phosphatase, bilirubin, urea nitrogen, or creatinine in icofungipen-treated
      rabbits. Icofungipen followed dose-dependent pharmacokinetics and was effective
      in the treatment of experimental disseminated candidiasis, including central
      nervous system infection, in persistently neutropenic rabbits.

PMID- 15855535
TI  - Pharmacokinetics of tenofovir in breast milk of lactating rhesus macaques.
AB  - To study tenofovir transfer into milk, two lactating macaques were given a
      subcutaneous dose of tenofovir (30 mg/kg of body weight). Peak concentrations and
      area under the curve values of tenofovir in milk were approximately 3 and
      approximately 20% of those detected in serum, respectively.

PMID- 15855536
TI  - Spread of a Klebsiella pneumoniae strain producing a plasmid-mediated ACC-1 AmpC
      beta-lactamase in a teaching hospital admitting disabled patients.
AB  - We describe a large outbreak involving a Klebsiella pneumoniae strain producing a
      plasmid-encoded ACC-1 type AmpC beta-lactamase in a hospital caring for patients
      with motor impairment. The epidemic strain was isolated from 57 patients in six
      wards between September 1999 and May 2003 and caused clinical infections in 19
      patients.

PMID- 15855537
TI  - Hypermutable and fluoroquinolone-resistant clinical isolates of Staphylococcus
      aureus.
AB  - Over 124 methicillin-susceptible Staphylococcus aureus 0/74 fluoroquinolone
      susceptible versus 5/50 fluoroquinolone-resistant isolates were hypermutable.
      Hypermutable isolates combined mutations in gyrA, parC, and/or parE genes. One
      strain had a large deletion of the mutator mutS and mutL genes. No relevant
      mutation in mutS and mutL genes was found in the other isolates.

PMID- 15855538
TI  - Origin and dissemination of chloroquine-resistant Plasmodium falciparum with
      mutant pfcrt alleles in the Philippines.
AB  - The pfcrt allelic type and adjacent microsatellite marker type were determined
      for 82 Plasmodium falciparum isolates from the Philippines. Mutant pfcrt allelic
      types P1a and P2a/P2b were dominant in different locations. Microsatellite
      analysis revealed that P2a/P2b evolved independently in the Philippines, while
      P1a shared common ancestry with Papua New Guinea chloroquine-resistant parasites.

PMID- 15855539
TI  - Florfenicol resistance gene floR is part of a novel transposon.
AB  - The florfenicol/chloramphenicol resistance gene floR was found to be part of the
      novel 4,284-bp transposon TnfloR from Escherichia coli. TnfloR consists of the
      gene floR, a putative regulatory gene, and the transposase gene tnpA. A circular
      form of TnfloR was detected and suggested the potential mobility of this
      transposon.

PMID- 15855540
TI  - Rapid inversion of the prevalences of macrolide resistance phenotypes paralleled
      by a diversification of T and emm types among Streptococcus pyogenes in Portugal.
AB  - In Portugal erythromycin resistance of 26.6% (n = 352) remained constant during
      1998 to 2003, however in 1998 the MLS(B) phenotype dominated (85%), whereas in
      2003 the M phenotype prevailed (77%). A decline in T12/emm22 MLS(B) isolates
      could partially explain the drop in this phenotype, but the rise of the M
      phenotype was not due to clonal expansion.

PMID- 15855541
TI  - Identification of a progenitor of the CTX-M-9 group of extended-spectrum beta
      lactamases from Kluyvera georgiana isolated in Guyana.
AB  - Chromosomal beta-lactamase genes (bla(KLUY)) from six Kluyvera georgiana strains
      isolated in Guyana were cloned and expressed in Escherichia coli. KLUY-1
      exhibited 100% amino acid identity with the extended-spectrum beta-lactamase CTX
      M-14. We also show that a 2.7-kb Kluyvera chromosomal region exhibits 99%
      nucleotide identity to a portion of In60 that includes bla(CTX-M-9).

PMID- 15855542
TI  - Evaluation of disk diffusion method for determining eberconazole susceptibility
      of dermatophytes and influence of culture medium.
AB  - We have evaluated a disk diffusion method to determine the activity of
      eberconazole against 50 strains of dermatophytes by testing three culture media
      (RPMI, antibiotic medium 3, and high resolution). No differences were found among
      the results obtained with the three media. A significant correlation between disk
      diffusion and microdilution methods was observed with AM3.

PMID- 15855543
TI  - Differences in interactions between azole drugs related to modifications in the
      14-alpha sterol demethylase gene (cyp51A) of Aspergillus fumigatus.
AB  - The combined activity of different azole drugs was investigated. Thirty-one
      Aspergillus fumigatus strains were tested, including two cyp51A(-) and one
      cyp51B(-) gene-knockout strain and azole-susceptible and -resistant strains with
      different resistance mechanisms. The combination of itraconazole and voriconazole
      was synergistic for all strains except for those with gene knockouts.

PMID- 15855544
TI  - Nationwide study of Escherichia coli and Klebsiella pneumoniae producing extended
      spectrum beta-lactamases in Spain.
AB  - Clonal dissemination of extended-spectrum beta-lactamases (ESBL) in 170
      Escherichia coli isolates and 70 Klebsiella pneumoniae isolates from a nationwide
      study of 40 Spanish centers in 2000 was not observed in most centers. The most
      prevalent ESBL were CTX-M-9 (27.3%), SHV-12 (23.9%), and CTX-M-14 (20.5%) for E.
      coli and TEM-3 (16.7%) and TEM-4 (25%) for K. pneumoniae. A new ESBL, TEM-133,
      with mutations L21F, E104K, and R164S, was identified.

PMID- 15855545
TI  - High genetic diversity of ciprofloxacin-nonsusceptible isolates of Streptococcus
      pneumoniae in Poland.
AB  - We have analyzed the susceptibility to ciprofloxacin of 697 pneumococcal isolates
      collected in 1998-2002 in Poland from patients with respiratory tract diseases.
      Thirty-one ciprofloxacin-nonsusceptible isolates (MICs, > or =4 microg/ml) were
      identified, of which two were resistant to levofloxacin (MIC, 8 microg/ml).
      Serotyping, pulsed-field gel electrophoresis, multilocus sequence typing, and the
      analysis of resistance determinants showed their great genetic diversity.

PMID- 15855546
TI  - Prevalence and characterization of invasive isolates of Streptococcus pyogenes
      with reduced susceptibility to fluoroquinolones.
AB  - Fluoroquinolone susceptibility testing was performed on invasive group A
      streptococcus isolates from 1992-1993 and 2003 from Ontario, Canada. None were
      nonsusceptible to levofloxacin. Two of 153 (1.3%) from 1992-1993 and 7 of 160
      (4.4%) from 2003 had a levofloxacin MIC of 2 mug/ml; all nine had parC mutations,
      and eight were serotype M6.

PMID- 15855548
TI  - High levels of antimicrobial coresistance among extended-spectrum-beta-lactamase
      producing Enterobacteriaceae.
AB  - We compared the susceptibility of 312 extended-spectrum beta-lactamase (ESBL)
      producing Enterobacteriaceae isolates with that of 1,216 ESBL nonproducers. Of
      ESBL producers, 25% were susceptible to gentamicin, 30% to trimethoprim
      sulfamethoxazole, 41% to ciprofloxacin, and 60% to piperacillin-tazobactam. ESBL
      nonproducers were more often susceptible to these agents. ESBL-producing
      Enterobacteriaceae represent a major source of resistance to various antibiotics.

PMID- 15855547
TI  - Substrate-dependent utilization of OprM or OpmH by the Pseudomonas aeruginosa
      MexJK efflux pump.
AB  - MexJK requires OprM for erythromycin efflux but not for triclosan efflux.
      Deletion of 15 OprM family outer membrane proteins (OMPs) revealed that only the
      TolC homolog OpmH functions with MexJK for triclosan efflux. This is the first
      report of natural utilization of multiple OMPs by a given resistance nodulation
      cell division transporter/membrane fusion protein pair.

PMID- 15855549
TI  - First isolation of blaVIM-2 in an environmental isolate of Pseudomonas
      pseudoalcaligenes.

PMID- 15855550
TI  - Salmonella enterica serovar infantis producing a CTX-M-9 beta-lactamase.

PMID- 15855551
TI  - Vibrio parahaemolyticus chromosomal qnr homologue VPA0095: demonstration by
      transformation with a mutated gene of its potential to reduce quinolone
      susceptibility in Escherichia coli.

PMID- 15855552
TI  - Further identification of plasmid-mediated quinolone resistance determinant in
      Enterobacteriaceae in Turkey.

PMID- 15855553
TI  - Nomenclature of GES-type extended-spectrum beta-lactamases.

PMID- 15855554
TI  - New antimicrobial agents approved by the U.S. Food and Drug Administration in
      2004 and new indications for previously approved agents.

PMID- 15855556
TI  - Glycemic control continues to deteriorate after sulfonylureas are added to
      metformin among patients with type 2 diabetes.
AB  - OBJECTIVE: To describe the course and predictors of glycemic control among
      patients with type 2 diabetes after sulfonylureas (SUs) are added to metformin
      (MF). RESEARCH DESIGN AND METHODS: Patients (n = 2,220) treated with MF
      monotherapy for >90 days before initiating MF plus SU combination therapy between
      January 1998 and March 2004 were studied in a retrospective analysis of
      electronic medical records from U.K. primary care practices using the General
      Practice Research Database. Median glycoslyated hemoglobin A(1c) (A1C) before and
      after SU initiation was described, and patient characteristics were evaluated as
      predictors of time until A1C > or =8.0% or glucose-lowering therapy was
      intensified (by starting insulin or adding a third oral agent). RESULTS: At 6
      months post-SU initiation, median A1C resumed deteriorating at a somewhat
      comparable rate to that observed on MF monotherapy. Higher pre-SU A1C, younger
      age, female sex, shorter diabetes duration, higher serum creatinine, and being an
      ex-smoker predicted time until A1C > or =8.0% or glucose-lowering therapy was
      intensified in various analyses. Median A1C was 9.5% when therapy was
      intensified. A1C > or =8.0% was estimated to occur in 85% of patients 4 years
      after SU initiation and in 68% 4 years after initially achieving A1C <7% on MF
      plus SU therapy. CONCLUSIONS: In this population, glycemic control is improved
      following the addition of SUs to MF, but deterioration resumes as early as 6
      months. The high proportion of patients remaining on MF plus SU therapy despite
      having A1C > or =8.0% suggests that there are significant barriers to starting
      insulin or adding a third agent when treatment goals are not achieved with this
      combination.

PMID- 15855557
TI  - Beta-cell response during a meal test: a comparative study of incremental doses
      of repaglinide in type 2 diabetic patients.
AB  - OBJECTIVE: To assess the effects of incremental doses of repaglinide on
      postprandial insulin and glucose profiles after a standard 500-kcal test meal.
      RESEARCH DESIGN AND METHODS: Sixteen diet-treated Caucasians with type 2 diabetes
      (mean HbA(1c) 8.4%) were enrolled in this randomized, open-label, crossover
      trial. Subjects received 0.5, 1, 2, and 4 mg repaglinide or placebo in a random
      fashion, followed by a standard 500-kcal test meal on 5 separate study days, 1
      week apart. RESULTS: The insulinogenic index (DeltaI30/DeltaG30) and insulin area
      under the curve (AUC) from 0 to 30 min (AUC(0-30)) were higher with the 4-mg drug
      dose compared with the two lower doses and with 2 mg compared with 0.5 mg. On
      subgroup analysis, the incremental insulin responses were apparent only in the
      fasting plasma glucose (FPG) < 9-mmol/l subgroup of subjects and not in the FPG
      >9-mmol/l subgroup. There was a significant dose-related increase in the late
      postprandial insulin secretion (insulin AUC(120-240)), which resulted in
      hypoglycemia in four subjects. Proinsulin-to-insulin ratios at 30 and 60 min
      improved with increasing doses of repaglinide; higher drug doses (2 and 4 mg)
      were more effective than the 0.5- and 1-mg doses. CONCLUSIONS: Significant dose
      related increases in early insulin secretion were found only in less advanced
      diabetic subjects. In advanced diabetic patients, only the maximum dose (4 mg)
      was significant compared with placebo. Better proinsulin-to-insulin processing
      was noted with increasing drug doses.

PMID- 15855558
TI  - Eliminating inpatient sliding-scale insulin: a reeducation project with medical
      house staff.
AB  - OBJECTIVE: We studied a systematic program to reeducate our medical house
      officers on how to manage inpatient hyperglycemia without the use of sliding
      scale insulin (SSI). RESEARCH DESIGN AND METHODS: Patients admitted to the
      general medical service with diabetes or a blood glucose >140 mg/dl were
      included. HbA(1c) was measured in all patients, and therapy was modified if the
      HbA(1c) was >7.0%. For each 24 h on call, two house officers were responsible for
      all glucose management for their team's patients and rounded with a teaching
      endocrinologist twice daily for 2 weeks. Oral agent or insulin therapy was
      modified using blood glucoses and HbA(1c). All patients who required insulin
      therapy were treated with basal and bolus insulin, usually NPH and regular,
      adjusted twice daily. RESULTS: During 8 weeks, 88 patients were identified and 16
      house officers were instructed. The mean duration of diabetes was 10.4 years.
      Mean HbA(1c) level was 8.7%, and 48% of patients had HbA(1c) >8%. All patients
      with HbA(1c) >7% had diabetes therapy intensified. Overall 80% had their diabetes
      therapy changed by discharge. Compared with 98 historical control subjects,
      significantly fewer study patients had episodes of hyperglycemia, and a subgroup
      followed for 12 months showed a decrease in HbA(1c) from 10.1 to 8%. CONCLUSIONS:
      Medical history, blood glucose, and HbA(1c) testing can effectively identify
      patients with inpatient hyperglycemia. Using direct ward-based teaching and a
      widely disseminated pocket set of guidelines, house officers can be taught to
      effectively and safely manage inpatient hyperglycemia without the use of SSI.

PMID- 15855559
TI  - Environmental correlates of physical activity among individuals with diabetes in
      the rural midwest.
AB  - OBJECTIVE: To determine the relationship between physical and social environment
      attributes and levels of physical activity in a population-based sample of
      diabetic individuals living in rural areas. RESEARCH DESIGN AND METHODS: Cross
      sectional telephone survey data from rural communities of southeastern Missouri,
      Tennessee, and Arkansas were used. Logistic regression was used to calculate
      crude and adjusted prevalence odds ratios (PORs) and 95% CIs. RESULTS: A total of
      278 (11%) individuals with diabetes were identified. Almost 37% of this group
      reported no leisure-time physical activity. Individuals with diabetes who
      reported regular physical activity were more likely to report better general
      health status, normal BMI, and no physical impairment. After adjustment, regular
      activity was positively associated with use of three or more facilities (POR
      14.3, 95% CI 3.0-67.3) in the past 30 days, the availability of many nearby
      places to walk (2.3, 1.1-4.8), the availability of shoulders on streets (2.4, 1.3
      4.5), often walking to nearby places (4.1, 2.0-8.3), and rating the community for
      physical activity as generally pleasant (2.3, 1.1-4.8). Additionally, the regular
      activity group was more likely to report their physician had helped make a plan
      to increase physical activity (2.8, 1.3-5.8) and followed up on their plan (2.2,
      1.1-4.4). Social environment variables were not associated with physical activity
      after adjustment. CONCLUSIONS: Physical inactivity is a significant problem in
      rural diabetic populations. We have identified aspects of the social and physical
      environment that are positively associated with physical activity. Understanding
      the role of the environment may result in increased physical activity for
      individuals with diabetes.

PMID- 15855560
TI  - Amputation prevention initiative in South India: positive impact of foot care
      education.
AB  - OBJECTIVE: To determine whether intensive treatment and education strategies for
      type 2 diabetic patients with high-risk diabetic foot disease helps in preventing
      foot amputations. RESEARCH DESIGN AND METHODS: Participants included 4,872
      consecutive type 2 diabetic patients (male-to-female ratio 3,422:1,450, mean (+/
      SD) age 60.5 +/- 8.8 years, mean duration of diabetes 13.7 +/- 7.6 years) with
      high-risk diabetic foot disease. The patients were categorized as high-risk
      subjects according to the International Consensus on the Diabetic Foot. The three
      study groups were subjects with diabetes and neuropathy (group 1; n = 2,871),
      diabetic neuropathy with deformity (group 2; n = 235), and diabetic neuropathy
      with deformity and foot ulceration or peripheral vascular disease (group 3; n =
      1,766). Neuropathy was diagnosed by biothesiometry. Peripheral vascular disease
      was diagnosed as an ankle brachial index <0.8. All the subjects were educated
      regarding diabetic foot disease and its complications and prevention. They were
      also instructed to visit the center if any sign of new lesions appeared. RESULTS:
      Among the 1,259 group 3 subjects who came for follow-up, 718 (57%) strictly
      followed the advice given and 541 (43%) did not. Ulcers present during the
      recruitment had healed in 585 (82%) subjects who followed the advice, but in only
      269 (50%) subjects who did not. A significantly larger proportion of subjects who
      did not follow the advice developed new problems (26%) and required surgical
      procedures (14%) compared with those who followed the advice (5 and 3%,
      respectively). CONCLUSIONS: Strategies such as intensive management and foot care
      education are helpful in preventing newer problems and surgery in diabetic foot
      disease.

PMID- 15855561
TI  - Dietary glycemic index, glycemic load, cereal fiber, and plasma adiponectin
      concentration in diabetic men.
AB  - OBJECTIVE: Adiponectin may improve insulin sensitivity, reduce inflammation, and
      ameliorate glycemic control. However, few studies have evaluated dietary
      predictors of plasma adiponectin levels, especially among subjects with type 2
      diabetes. RESEARCH DESIGN AND METHODS: To examine the associations of dietary
      glycemic load, glycemic index, and fibers with plasma adiponectin levels, we
      conducted a cross-sectional analysis in 780 diabetic men from the Health
      Professionals' Follow-up Study. Dietary information was obtained in 1986, 1990,
      and 1994 using semiquantitative food-frequency questionnaires. RESULTS: After
      adjustment for age, BMI, smoking, alcohol consumption, physical activity, aspirin
      use, HbA(1c), history of hypertension or hypercholesterolemia, and fiber intake,
      dietary glycemic index and glycemic load were inversely associated with plasma
      adiponectin in a dose-dependent fashion (P for trend = 0.005 for glycemic index
      and 0.004 for glycemic load). Adiponectin levels were 13% lower in the highest
      quintile of dietary glycemic index than in the lowest quintile. For dietary
      glycemic load, adiponectin levels were 18% lower in the highest quintile than in
      the lowest. In contrast, high intake of cereal fiber was associated with
      increased plasma adiponectin levels, adjusting for lifestyle factors and dietary
      glycemic load (P for trend = 0.003). Adiponectin levels were 19% higher in the
      highest quintile than in the lowest quintile. Higher magnesium intake was also
      associated with increased plasma adiponectin. CONCLUSIONS: Diets low in glycemic
      load and high in fiber may increase plasma adiponectin concentrations in diabetic
      patients.

PMID- 15855562
TI  - The challenge of achieving national cholesterol goals in patients with diabetes.
AB  - OBJECTIVE: This study analyzed lipid results from a large community-based
      population of patients with diabetes to assess the feasibility of attaining the
      standard and new optional LDL-based lipid goals using currently available lipid
      lowering medications. RESEARCH DESIGN AND METHODS: Ambulatory patients with
      diabetes who were interviewed as part of the Vermont Diabetes Information System
      trial with a reported LDL were analyzed. Patients were categorized into high-risk
      and very-high-risk cardiovascular status. For patients not at the LDL goal, the
      required changes in therapy to achieve the goal were assessed. RESULTS: Of the
      entire cohort, 49.4% (321 of 650) had LDL <100 mg/dl. According to the National
      Cholesterol Education Program, 29.4% (191 of 650) of patients were very high risk
      and have an optional LDL goal of <70 mg/dl. Only 15.7% (30 of 191) of very-high
      risk patients had an LDL <70 mg/dl. Based on our analysis of high-risk patients,
      17 of 459 (3.7%) would require more than two lipid-lowering drugs to achieve an
      LDL <100 mg/dl. In the very-high-risk group, we estimate that 26.2% (50 of 191)
      of patients will not reach LDL <70 mg/dl with two lipid-lowering medications.
      CONCLUSIONS: In many patients with diabetes and cardiovascular disease, it will
      be difficult to attain an LDL goal of <70 mg/dl. Approximately 25% of patients
      will require more than two lipid-lowering drugs at maximal doses to attain this
      goal, assuming 100% tolerance of lipid-lowering medications.

PMID- 15855563
TI  - Pregnancy experience among women with and without gestational diabetes in the
      U.S., 1995 National Survey Of Family Growth.
AB  - OBJECTIVE: To compare the pregnancy experience among women with and without
      gestational diabetes mellitus (GDM) using a nationally representative survey.
      RESEARCH DESIGN AND METHODS: We analyzed data from the 1995 National Survey of
      Family Growth conducted by National Center for Health Statistics on 3,088 women
      age 15-44 years with at least one pregnancy between 1991 and 1995 to compare
      demographics, fecundity, and pregnancy experience by GDM (n = 116) or nondiabetes
      (n = 2,969) status. RESULTS: Among women with a pregnancy during 1991-1995, 3.6%
      reported GDM history. Women with GDM were older at age of delivery (31.8 years)
      than women without diabetes (29.0 years, P < 0.001). There was no significant
      difference between the groups by race/ethnicity. Compared with women without
      diabetes, women with gestational diabetes were more likely to report being
      currently surgically sterile (20.4 vs. 32.6%) or having impaired fecundity (12.6
      vs. 19.7%, P < 0.001). GDM patients were more likely to have had a caesarean
      section than those without diabetes (31.7 vs. 20.9%, P = 0.02) and were more
      likely to report at least one of six additional nonroutine medical complications
      during pregnancy than nondiabetic patients (48.8 vs. 17.1%, P < 0.001). The odds
      ratio of a maternal medical complication during pregnancy for women with GDM
      compared with nondiabetic women, after adjusting for age at pregnancy and
      nongestational hypertension, was 4.3 (95% CI 2.7-6.8). CONCLUSIONS: These
      findings suggest that pregnancies in women with GDM are more likely to be
      associated with maternal medical complications compared with pregnancies in women
      without diabetes.

PMID- 15855564
TI  - End-stage renal disease due to diabetes among southwestern American Indians, 1990
      2001.
AB  - OBJECTIVE: This study assesses trends in the incidence of diabetes-related end
      stage renal disease (ESRD) among southwestern American Indians (SWAIs). RESEARCH
      DESIGN AND METHODS: Using the U.S. Renal Data System, we obtained the total
      number of new cases of treated ESRD in which diabetes was the primary cause of
      renal failure in 1990 through 2001. The incidence of diabetes-related ESRD was
      calculated using census population figures and estimates of the SWAI population
      with diabetes, then age-adjusted to the 2000 U.S. population. RESULTS: Between
      1990 and 2001, the annual number of new patients starting treatment for diabetes
      related ESRD in the SWAI total population increased from 154 to 320, and the age
      adjusted diabetes-related ESRD incidence per 10,000 population increased 34% (6.2
      8.3 per 10,000 people). However, after adjusting for the increasing number of
      people with diabetes in the SWAI population between 1993 and 2001, the age
      adjusted incidence of diabetes-related ESRD among SWAIs with diabetes decreased
      31%, from 80.4 to 55.8 per 10,000 people with diabetes. It decreased for both
      sexes and in all age-groups. CONCLUSIONS: The increasing incidence of diabetes
      related ESRD in the SWAI population parallels the growing prevalence of diabetes.
      However, since 1993 diabetes-related ESRD incidence decreased in the SWAI
      population with diabetes, consistent with national trends. This may reflect the
      reduction in risk factors and improvements in diabetes care practices in Indian
      communities.

PMID- 15855565
TI  - Time trends and geographic disparities in acute complications of diabetes in
      Ontario, Canada.
AB  - OBJECTIVE: This study examines whether acute diabetes complication rates have
      fallen in recent years and whether geographic factors influence these trends.
      RESEARCH DESIGN AND METHODS: A population-based time-trend analysis of acute
      complications of diabetes was conducted using linked administrative and census
      data from Ontario, Canada. The study population included all adults identified
      through a province-wide electronic diabetes registry between 1994 and 1999 (n =
      577,659). The primary outcome was hospitalizations for hyper- and hypoglycemia
      and emergency department visits for diabetes. RESULTS: Between 1994 and 1999,
      rates of hospitalization for hyper- and hypoglycemic emergencies decreased by
      32.5 and 76.9%, respectively; emergency department visits for diabetes fell by
      23.9%. On multivariate analysis, fiscal year was an independent predictor of
      acute diabetes complications, with individuals in our cohort experiencing a
      decline in risk of approximately 6% per year for either being hospitalized with
      hyper- or hypoglycemia or requiring an emergency department visit for diabetes.
      After accounting for variation in physician service use, diabetic individuals
      living in rural areas or Aboriginal communities were nearly twice as likely to
      have an acute complication, whereas those residing in remote areas of the
      province were nearly three times as likely to experience an event. CONCLUSIONS:
      Although our findings suggest an overall improvement in diabetes care in Ontario,
      certain subgroups of the population continue to experience higher rates of
      complications that are potentially preventable through good ambulatory care.
      Measures to improve access to timely and effective outpatient care may further
      reduce rates of acute complications among the diabetic population.

PMID- 15855566
TI  - Awareness and treatment of dyslipidemia in young adults with type 1 diabetes.
AB  - OBJECTIVE: Dyslipidemia is a preventable major risk factor for coronary heart
      disease (CHD). Despite an increased risk of CHD in type 1 diabetes, little is
      known concerning awareness and adequacy of dyslipidemia treatment in this
      population. In this report, we describe the prevalence of dyslipidemia and
      adequacy of pharmacological treatment in patients with type 1 diabetes and
      comparable nondiabetic subjects. RESEARCH DESIGN AND METHODS: From 2000 to 2002,
      the Coronary Artery Calcification in Type 1 Diabetes study obtained fasting lipid
      profiles in 1,416 individuals aged 19-56 years with no history of CHD: 652 type 1
      diabetic patients (46% men, mean age 37 +/- 9 years) and 764 nondiabetic control
      subjects (50% men, mean age 39 +/- 9 years). These data combined with patient
      questionnaire results were used to determine prevalence of dyslipidemia and
      adequacy of pharmacological treatment. For all subjects, dyslipidemia was defined
      using National Cholesterol Education Program Adult Treatment Panel III criteria.
      RESULTS: Type 1 diabetic subjects had significantly less dyslipidemia than
      nondiabetic control subjects (47 vs. 58%, P < 0.001), and a higher percentage of
      those with abnormal lipids were aware of (52 vs. 34%, P < 0.0001), on medication
      for (36 vs. 9%, P < 0.0001), and in control of their lipid levels (15 vs. 1.4%, P
      < 0.001). Of those on treatment, control was achieved in 41% of type 1 diabetic
      subjects and 15% of nondiabetic participants (P < 0.01). CONCLUSIONS:
      Dyslipidemia, a major risk factor for CHD, remains largely undiagnosed and
      undertreated in high-risk populations, such as patients with type 1 diabetes.

PMID- 15855567
TI  - One-hour postload plasma glucose in middle age and Medicare expenditures in older
      age among nondiabetic men and women: the Chicago Heart Association Detection
      Project in Industry.
AB  - OBJECTIVE: To examine associations in nondiabetic individuals of 1-h postload
      plasma glucose measured in young adulthood and middle age with subsequent
      Medicare expenditures for cardiovascular disease (CVD), diabetes, cancer, and all
      health care at age 65 years or older using data from the Chicago Heart
      Association Detection Project in Industry (CHA). RESEARCH DESIGN AND METHODS:
      Medicare data (1984-2000) were linked with CHA baseline records (1967-1973) for
      8,580 men and 6,723 women ages 33-64 years who were free of coronary heart
      disease, diabetes, and major electrocardiogram (ECG) abnormalities and who were
      Medicare eligible (65+ years) for at least 2 years. Participants were classified
      based on 1-h postload plasma glucose levels <120, 120-199, or > or =200 mg/dl.
      RESULTS: With adjustment for baseline age, cigarette smoking, serum cholesterol,
      systolic blood pressure, BMI, ethnicity, education, and minor ECG abnormalities,
      the average annual and cumulative Medicare, total, and diabetes- and CVD-related
      charges were significantly higher with higher baseline plasma glucose in women,
      while only diabetes-related charges were significantly higher in men. For
      example, in women, multivariate-adjusted CVD-related cumulative charges were,
      respectively, USD 14,260, 18,909, and 21,183 for the three postload plasma
      glucose categories (P value for trend = 0.035). CONCLUSIONS: These findings
      suggest that maintaining low glucose levels early in life has the potential to
      reduce health care costs in older age.

PMID- 15855568
TI  - History of depression increases risk of type 2 diabetes in younger adults.
AB  - OBJECTIVE: The purpose of this study was to assess the history of previous
      depression in people with incident diabetes compared with people without
      diabetes. RESEARCH DESIGN AND METHODS: We conducted a population-based nested
      case-control study using the administrative databases of Saskatchewan Health to
      assess the study objective. We identified cases of type 2 diabetes based on
      diagnostics codes and prescription records for individuals over the age of 20
      years. For each case subject, two control subjects were randomly selected from
      the nondiabetic population during the same index year. History of depression,
      based on diagnostic codes and antidepressant prescription, was ascertained up to
      3 years before index date. Simple and multivariate logistic regression analysis
      was used to estimate the odds ratio (OR) and 95% CIs, after adjusting for age,
      sex, and frequency of physician visits. RESULTS: Individuals with newly diagnosed
      diabetes (1,622 of 33,257; 4.9%) were 30% more likely to have had a previous
      history of depression compared with people without diabetes (2,279 of 59,420;
      3.8%). This increased risk remained after controlling for sex and number of
      physician visits but was limited to subjects 20-50 years of age (adjusted OR 1.23
      [95% CI 1.10-1.37]) and not in those aged > or =51 years (0.92 [0.84-1.00]).
      CONCLUSIONS: Depression appears to increase the risk of developing diabetes by
      approximately 23% in younger adults. This provides information regarding the
      temporality of the relationship between diabetes and depression.

PMID- 15855569
TI  - Effects of oral insulin in relatives of patients with type 1 diabetes: The
      Diabetes Prevention Trial--Type 1.
AB  - OBJECTIVE: This randomized, double-masked, placebo-controlled clinical trial
      tested whether oral insulin administration could delay or prevent type 1 diabetes
      in nondiabetic relatives at risk for diabetes. RESEARCH DESIGN AND METHODS: We
      screened 103,391 first- and second-degree relatives of patients with type 1
      diabetes and analyzed 97,273 samples for islet cell antibodies. A total of 3,483
      were antibody positive; 2,523 underwent genetic, immunological, and metabolic
      staging to quantify risk of developing diabetes; 388 had a 5-year risk projection
      of 26-50%; and 372 (median age 10.25 years) were randomly assigned to oral
      insulin (7.5 mg/day) or placebo. Oral glucose tolerance tests were performed
      every 6 months. The median follow-up was 4.3 years, and the primary end point was
      diagnosis of diabetes. RESULTS: Diabetes was diagnosed in 44 oral insulin and 53
      placebo subjects. Annualized rate of diabetes was similar in both groups: 6.4%
      with oral insulin and 8.2% with placebo (hazard ratio 0.764, P = 0.189). In a
      hypothesis-generating analysis of a subgroup with insulin autoantibody (IAA)
      levels confirmed (on two occasions) > or =80 nU/ml (n = 263), there was the
      suggestion of benefit: annualized diabetes rate 6.2% with oral insulin and 10.4%
      with placebo (0.566, P = 0.015). CONCLUSIONS: It is possible to identify
      individuals at high risk for type 1 diabetes and to enroll them in a large,
      multisite, randomized, controlled clinical trial. However, oral insulin did not
      delay or prevent type 1 diabetes. Further studies are needed to explore the
      potential role of oral insulin in delaying diabetes in relatives similar to those
      in the subgroup with higher IAA levels.

PMID- 15855570
TI  - Time-action profile of inhaled insulin in comparison with subcutaneously injected
      insulin lispro and regular human insulin.
AB  - OBJECTIVE: This study compares the time-action profile of inhaled insulin (INH;
      Exubera) with that of subcutaneously injected insulin lispro (ILP) or regular
      human insulin (RHI) in healthy volunteers. RESEARCH DESIGN AND METHODS: In this
      open-label, randomized, three-way, crossover study, 17 healthy male volunteers
      were given each of the following treatments in random order: INH (6 mg), ILP (18
      units), or RHI (18 units). Glucose infusion rates and serum insulin
      concentrations were monitored over 10 h. RESULTS: INH had a faster onset of
      action than both RHI and ILP, as indicated by shorter time to early half-maximal
      effect (32 vs. 48 and 41 min, respectively; P < 0.001 for IHN vs. RHI and P <
      0.05 for IHN vs. ILP). Time to maximal effect was comparable between INH and ILP
      (143 vs. 137 min; NS) but was shorter for INH than RHI (193 min; P < 0.01). The
      maximal metabolic effect of INH was comparable with RHI but lower than ILP (8.7
      vs. 9.8 vs. 11.2 mg . kg(-1) . min(-1), respectively; P < 0.01 for INH vs. ILP).
      The duration of action of INH, indicated by time to late half-maximal effect (387
      min), was longer than ILP (313 min; P < 0.01) and comparable to RHI (415 min;
      NS). Total glucodynamic effect after inhalation of INH was comparable to both ILP
      and RHI (NS). Relative bioefficacy of INH was 10% versus RHI and 11% versus ILP.
      No drug-related adverse events were observed. CONCLUSIONS: INH had a faster onset
      of action than RHI or ILP and a duration of action longer than ILP and comparable
      to RHI. These characteristics suggest that inhaled insulin is suitable for
      prandial insulin supplementation in patients with diabetes.

PMID- 15855571
TI  - Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients
      with type 2 diabetes treated with metformin and a sulfonylurea.
AB  - OBJECTIVE: This study evaluated the effects of exenatide, a novel incretin
      mimetic, in hyperglycemic patients with type 2 diabetes unable to achieve
      glycemic control with metformin-sulfonylurea combination therapy. RESEARCH DESIGN
      AND METHODS: A 30-week, double-blind, placebo-controlled study was performed in
      733 subjects (aged 55 +/- 10 years, BMI 33.6 +/- 5.7 kg/m(2), A1C 8.5 +/- 1.0%;
      means +/- SD) randomized to 5 microg subcutaneous exenatide b.i.d. (arms A and B)
      or placebo for 4 weeks. Thereafter, arm A remained at 5 microg b.i.d. and arm B
      escalated to 10 microg b.i.d. Subjects continued taking their dose of metformin
      and were randomized to either maximally effective (MAX) or minimum recommended
      (MIN) doses of sulfonylurea. RESULTS: Week 30 A1C changes from baseline (+/-SE)
      were -0.8 +/- 0.1% (10 microg), -0.6 +/- 0.1% (5 microg), and +0.2 +/- 0.1%
      (placebo; adjusted P < 0.0001 vs. placebo), yielding placebo-adjusted reductions
      of -1.0% (10 microg) and -0.8% (5 microg). In the evaluable population, exenatide
      treated subjects were more likely to achieve A1C < or =7% than placebo-treated
      subjects (34% [10 microg], 27% [5 microg], and 9% [placebo]; P < 0.0001). Both
      exenatide arms demonstrated significant weight loss (-1.6 +/- 0.2 kg from
      baseline each exenatide arm, -0.9 +/- 0.2 kg placebo; P < or = 0.01 vs. placebo).
      Mild or moderate nausea was the most frequent adverse event. The incidence of
      mild/moderate hypoglycemia was 28% (10 microg), 19% (5 microg), and 13% (placebo)
      and appeared lower with MIN than with MAX sulfonylurea treatment. CONCLUSIONS:
      Exenatide significantly reduced A1C in patients with type 2 diabetes unable to
      achieve adequate glycemic control with maximally effective doses of combined
      metformin-sulfonylurea therapy. This improvement in glycemic control was
      associated with no weight gain and was generally well tolerated.

PMID- 15855572
TI  - Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in
      metformin-treated patients with type 2 diabetes.
AB  - OBJECTIVE: This study evaluates the ability of the incretin mimetic exenatide
      (exendin-4) to improve glycemic control in patients with type 2 diabetes failing
      to achieve glycemic control with maximally effective metformin doses. RESEARCH
      DESIGN AND METHODS: A triple-blind, placebo-controlled, 30-week study at 82 U.S.
      sites was performed with 336 randomized patients. In all, 272 patients completed
      the study. The intent-to-treat population baseline was 53 +/- 10 years with BMI
      of 34.2 +/- 5.9 kg/m(2) and HbA(1c) of 8.2 +/- 1.1%. After 4 weeks of placebo,
      subjects self-administered 5 microg exenatide or placebo subcutaneously twice
      daily for 4 weeks followed by 5 or 10 microg exenatide, or placebo subcutaneously
      twice daily for 26 weeks. All subjects continued metformin therapy. RESULTS: At
      week 30, HbA(1c) changes from baseline +/- SE for each group were -0.78 +/- 0.10%
      (10 microg), -0.40 +/- 0.11% (5 microg), and +0.08 +/- 0.10% (placebo; intent to
      treat; adjusted P < 0.002). Of evaluable subjects, 46% (10 microg), 32% (5
      microg), and 13% (placebo) achieved HbA(1c) < or =7% (P < 0.01 vs. placebo).
      Exenatide-treated subjects displayed progressive dose-dependent weight loss (-2.8
      +/- 0.5 kg [10 microg], -1.6 +/- 0.4 kg [5 microg]; P < 0.001 vs. placebo). The
      most frequent adverse events were gastrointestinal in nature and generally mild
      to moderate. Incidence of mild to moderate hypoglycemia was low and similar
      across treatment arms, with no severe hypoglycemia. CONCLUSIONS: Exenatide was
      generally well tolerated and reduced HbA(1c) with no weight gain and no increased
      incidence of hypoglycemia in patients with type 2 diabetes failing to achieve
      glycemic control with metformin.

PMID- 15855573
TI  - A randomized multicenter trial comparing the GlucoWatch Biographer with standard
      glucose monitoring in children with type 1 diabetes.
AB  - OBJECTIVE: This study assesses whether use of the GlucoWatch G2 Biographer (GW2B)
      in addition to standard glucose monitoring lowers HbA(1c) and reduces
      hypoglycemia compared with standard glucose monitoring alone. RESEARCH DESIGN AND
      METHODS: In all, 200 subjects aged 7 to <18 years with type 1 diabetes were
      randomly assigned at five centers to standard glucose monitoring (usual care) or
      standard glucose monitoring plus GW2B use for 6 months. Study outcomes included
      HbA(1c) values obtained at 6 months and occurrence of severe hypoglycemia.
      RESULTS: The mean HbA(1c) at baseline was 8.0% in both groups; at 6 months,
      HbA(1c) was 7.9% in the usual care group and 8.1% in the GW2B group (95% CI for
      mean reduction in the GW2B group compared with the usual care group -0.4 to 0.1%;
      P = 0.15). A decrease in HbA(1c) of > or =0.5% was achieved in 21% of the usual
      care group and 28% of the GW2B group (P = 0.29). Severe hypoglycemia events
      occurred in 7% of the GW2B group and in 2% of the usual care group (P = 0.10). In
      the GW2B group, sensor use declined throughout the study from a mean value of 2.1
      times/week in the 1st month to 1.5 times/week in the 6th month. Reasons given for
      declining use included skin irritation (76%), frequent skips (56%), excessive
      alarms (47%), and inaccurate readings (33%). CONCLUSIONS: Use of the GW2B in
      addition to standard glucose monitoring did not improve glycemic control or
      reduce the frequency of severe hypoglycemia. Skin reactions and other problems
      led to decreasing sensor use over time.

PMID- 15855574
TI  - A double-blind, randomized, dose-response study investigating the pharmacodynamic
      and pharmacokinetic properties of the long-acting insulin analog detemir.
AB  - OBJECTIVE: To investigate the pharmacodynamic profile and duration of action for
      five subcutaneous doses of insulin detemir (0.1, 0.2, 0.4, 0.8, and 1.6 units/kg;
      1 unit = 24 nmol) and one subcutaneous dose of NPH insulin (0.3 IU/kg; 1 IU = 6
      nmol). RESEARCH DESIGN AND METHODS: This single-center, randomized, double-blind,
      six-period, crossover study was carried out as a 24-h isoglycemic clamp (7.2
      mmol/l) in 12 type 1 diabetic patients. RESULTS: Duration of action for insulin
      detemir was dose dependent and varied from 5.7, to 12.1, to 19.9, to 22.7, to
      23.2 h for 0.1, 0.2, 0.4, 0.8, and 1.6 units/kg, respectively. Interpolation of
      the dose-response relationships for AUC(GIR) (area under the glucose infusion
      rate curve) revealed that a detemir dose of 0.29 units/kg would provide the same
      effect as 0.3 IU/kg NPH but has a longer duration of action (16.9 vs. 12.7 h,
      respectively). Lower between-subject variability was observed for insulin detemir
      on duration of action (0.4 units/kg insulin detemir vs. 0.3 IU/kg NPH, P < 0.05)
      and GIR(max) (maximal glucose infusion rate) (0.2 and 0.4 units/kg insulin
      detemir vs. 0.3 IU/kg NPH, both P < 0.05). Assessment of endogenous glucose
      production (EGP) and peripheral glucose uptake (PGU) resulted in an AOC(EGP)
      (area over the EGP curve) of 636 mg/kg (95% CI 279-879) vs. 584 (323-846) and an
      AUC(PGU) (area under the PGU curve) of 173 (47-316) vs. 328 (39-617) for 0.29
      units/kg detemir vs. 0.3 IU/kg NPH, respectively. CONCLUSIONS: This study shows
      that insulin detemir provides a flat and protracted pharmacodynamic profile.

PMID- 15855575
TI  - Elevated pregnancy losses at high and low extremes of maternal glucose in early
      normal and diabetic pregnancy: evidence for a protective adaptation in diabetes.
AB  - OBJECTIVE: Early pregnancy losses increase with marked hyperglycemia in diabetic
      pregnancy. However, mean loss rates do not differ from those of nondiabetic
      pregnancy. This observation might be explained by increased fetal losses at the
      extremes of glycemia in diabetic and nondiabetic pregnancy. To test this
      hypothesis, we examined relationships of proximate measures of prior glycemia,
      glycated protein and fructosamine, to pregnancy loss. RESEARCH DESIGN AND
      METHODS: A total of 389 diabetic and 429 nondiabetic pregnant subjects
      participated in the Diabetes In Early Pregnancy study. Glycated protein and
      fructosamine measurements were standardized as multiples of control values for
      each center (Z score). The logarithm of odds of pregnancy loss were plotted
      against Z scores and tested by logistic models. RESULTS: Mean pregnancy loss
      rates were 12% in diabetic and 13% in normal pregnancies. However, over six
      intervals of glycated protein in diabetic pregnancy, fetal loss rates at the
      upper and lower extremes (24 and 33%, respectively) were approximately threefold
      higher than the four intervening rates (8-14%). The odds ratio of pregnancy loss
      for these extreme intervals to the intervening intervals is 3.0 (P = 0.01).
      Nondiabetic losses showed a similar pattern. In confirmation, logit pregnancy
      losses were increased in a J-shaped curve at the glycemic extremes in normal (P <
      0.019) and diabetic (P < 0.015) pregnancy. The upper glycemic extreme in diabetic
      pregnancy was two- to fivefold higher than in control pregnancy. CONCLUSIONS:
      Pregnancy losses are increased at the extremes of glycemia in both normal and
      diabetic pregnancy but at higher levels in diabetic pregnancy. The data suggest
      defensive adaptations against hyperglycemia in diabetic pregnancy.

PMID- 15855576
TI  - Anemia and diabetes in the absence of nephropathy.
AB  - OBJECTIVE: Patients with diabetes commonly have a greater degree of anemia for
      their level of renal impairment than those presenting with other causes of renal
      failure. To clarify the contribution and differing roles of diabetes and
      nephropathy in the development of anemia in diabetic patients, we examined the
      hematologic and hematinic parameters of diabetic patients without nephropathy.
      RESEARCH DESIGN AND METHODS: The study group was comprised of 62 patients with
      type 2 diabetes who had been followed for a median of 7 years. For the study,
      these patients had additional samples taken during their annual routine blood
      testing for the measurement of extra parameters, including serum ferritin, serum
      erythropoietin (Epo) levels, and the percentage of reticulocytes. These
      measurements were combined with the routine parameters Hb, hematocrit, HbA(1c),
      and glomerular filtration rate. RESULTS: In all, 8 of the 45 male patients
      (17.8%) and 2 of the 17 female patients (11.8%) were classified as anemic (Hb
      <13g/dl and <11.5g/dl, respectively). Although only a small number of the
      patients had anemia as defined by normal values, a retrospective analysis of
      individual patients over time revealed a sustained though small decrease in Hb
      from initial presentation. A statistically significant difference in Epo levels
      (P = 0.016 by Kruskal-Wallis test) was observed from the group with the lowest
      (Hb < or =11.5) to that with the highest (Hb > or =14.5) Hb values, with a median
      Epo value of 37 (interquartile range 24-42) vs. 13 (9-15) IU/l, respectively. In
      contrast, there was no evidence of an increased reticulocyte response to higher
      levels of Epo (r = 0.134 [Pearsons], P = 0.36). Reticulocyte counts ranged from
      44 (38-57) to 76.5 (56-83) in the lowest and highest Hb groups, respectively.
      CONCLUSIONS: Although only a small number of subjects in the group were overtly
      anemic, all subjects had an ongoing, small but significant decrease in Hb since
      presentation. This study of diabetic patients without nephropathy shows an
      expected increase in Epo production in response to lowering levels of Hb but
      without the expected reticulocyte response.

PMID- 15855577
TI  - Role of the decrement in intraislet insulin for the glucagon response to
      hypoglycemia in humans.
AB  - OBJECTIVE: Animal and in vitro studies indicate that a decrease in beta-cell
      insulin secretion, and thus a decrease in tonic alpha-cell inhibition by
      intraislet insulin, may be an important factor for the increase in glucagon
      secretion during hypoglycemia. However, in humans this role of decreased
      intraislet insulin is still unclear. RESEARCH DESIGN AND METHODS: We studied
      glucagon responses to hypoglycemia in 14 nondiabetic subjects on two separate
      occasions. On both occasions, insulin was infused from 0 to 120 min to induce
      hypoglycemia. On one occasion, somatostatin was infused from -60 to 60 min to
      suppress insulin secretion, so that the decrement in intraislet insulin during
      the final 60 min of hypoglycemia would be reduced. On the other occasion,
      subjects received an infusion of normal saline instead of the somatostatin.
      RESULTS: During the 2nd h of the insulin infusion, when somatostatin or saline
      was no longer being infused, plasma glucose ( approximately 2.6 mmol/l) and
      insulin levels ( approximately 570 pmol/l) were comparable in both sets of
      experiments (both P > 0.4). In the saline experiments, insulin secretion remained
      unchanged from baseline (-90 to -60 min) before insulin infusion and decreased
      from 1.20 +/- 0.12 to 0.16 +/- 0.04 pmol . kg(-1) . min(-1) during insulin
      infusion (P < 0.001). However, in the somatostatin experiments, insulin secretion
      decreased from 1.18 +/- 0.12 pmol . kg(-1) . min(-1) at baseline to 0.25 +/- 0.09
      pmol . kg(-1) . min(-1) before insulin infusion so that it did not decrease
      further during insulin infusion (-0.12 +/- 0.10 pmol . kg(-1) . min(-1), P =
      0.26) indicating the complete lack of a decrement in intraislet insulin during
      hypoglycemia. This was associated with approximately 30% lower plasma glucagon
      concentrations (109 +/- 7 vs. 136 +/- 9 pg/ml, P < 0.006) and increments in
      plasma glucagon above baseline (41 +/- 8 vs. 67 +/- 11 pg/ml, P < 0.008) during
      the last 15 min of the hypoglycemic clamp. In contrast, increases in plasma
      growth hormone were approximately 70% greater during hypoglycemia after
      somatostatin infusion (P < 0.007), suggesting that to some extent the increases
      in plasma glucagon might have reflected a rebound in glucagon secretion.
      CONCLUSIONS: These results provide direct support for the intraislet insulin
      hypothesis in humans. However, the exact extent to which a decrement in
      intraislet insulin accounts for the glucagon responses to hypoglycemia remains to
      be established.

PMID- 15855578
TI  - Beta-cell function in mild type 2 diabetic patients: effects of 6-month glucose
      lowering with nateglinide.
AB  - OBJECTIVE: We studied the effects of the oral insulin secretagogue nateglinide on
      insulin secretion using a modeling approach to obtain beta-cell function
      parameters from a meal test and examined the impact of the beta-cell improvement
      on glucose tolerance. RESEARCH DESIGN AND METHODS: Mild type 2 diabetic men and
      women (n = 108; fasting glucose 7.0-8.3 mmol/l) on diet treatment alone randomly
      received 30, 60, or 120 mg nateglinide or placebo for 24 weeks. Beta-cell
      function parameters were derived by modeling (based on C-peptide deconvolution)
      from a standardized meal test at baseline and after 24 weeks of treatment.
      RESULTS: The baseline demographic and metabolic characteristics of the four
      groups were similar. Nateglinide treatment resulted in dose-dependent reductions
      in the mean postprandial glucose response and at the 120-mg dose in fasting
      glucose. Fasting or total insulin secretion during the meal were not different.
      In contrast, we found differences in the model parameters. Rate sensitivity
      (expressing early insulin secretion when glucose is rising) was significantly
      enhanced at 24 weeks with the lowest nateglinide dose, with no further
      stimulation at higher doses. Early potentiation (expressing an initial insulin
      secretion enhancement), glucose sensitivity (the slope of the glucose-insulin
      secretion relationship), and insulin secretion at a fixed- reference 7-mmol/l
      glucose concentration all showed a trend toward increasing, with increasing
      nateglinide dose, and were significantly greater than placebo at the 120-mg dose.
      In multiple regression analyses, changes in rate sensitivity, glucose
      sensitivity, and potentiation all contributed to the observed glucose changes.
      CONCLUSIONS: The model-derived parameters are sensitive measures of beta-cell
      function, showing improvements after nateglinide treatment and predicting changes
      in glucose tolerance.

PMID- 15855579
TI  - The influence of adiponectin gene polymorphism on the rosiglitazone response in
      patients with type 2 diabetes.
AB  - OBJECTIVE: The aim of this study was to examine the effects of rosiglitazone on
      adiponectin and plasma glucose levels in relation with common adiponectin gene
      (ACDC) polymorphisms. RESEARCH DESIGN AND METHODS: A total of 166 patients with
      type 2 diabetes were treated with rosiglitazone (4 mg/day) for 12 weeks without
      changing any of their previous medications. In all, single nucleotide
      polymorphism (SNP)45 and SNP276 of ACDC were examined. RESULTS: Regarding SNP45,
      there was a smaller reduction in the fasting plasma glucose (FPG) level and the
      HbA(1c) value in the carriers of the GG genotype than in the carriers of the
      other genotypes (P = 0.031 and 0.013, respectively). There was a smaller increase
      in the serum adiponectin concentration for the GG genotype than for the other
      genotypes (P = 0.003). Regarding SNP276, there was less reduction in the FPG
      level for the GG genotype than for the other genotypes (P = 0.001). In the
      haplotype analysis, the reductions in the FPG and HbA(1c) levels were smaller for
      the GG homozygote haplotype than for the other haplotypes (P = 0.001 and 0.001,
      respectively). The increase in the plasma adiponectin concentration for the GG
      homozygote haplotype was smaller than that of the other haplotypes (P = 0.003).
      CONCLUSIONS: These data suggest that genetic variations in the adiponectin gene
      can affect the rosiglitazone treatment response of the circulating adiponectin
      level and blood glucose control in type 2 diabetic patients.

PMID- 15855580
TI  - Effect of a peroxisome proliferator-activated receptor-gamma agonist on
      myocardial blood flow in type 2 diabetes.
AB  - OBJECTIVE: The relationship between coronary endothelial function and insulin
      resistance remains speculative. We sought to determine whether pioglitazone, an
      insulin-sensitizing peroxisome proliferator-activated receptor (PPAR)-gamma
      agonist, improves cardiac endothelial function in individuals with type 2
      diabetes. RESEARCH DESIGN AND METHODS: Sixteen subjects with insulin-treated type
      2 diabetes and without overt cardiovascular disease were randomly assigned to
      receive either 45 mg of pioglitazone or matching placebo for 3 months. Rest and
      adenosine-stimulated myocardial blood flow (MBF) were quantified with
      [(13)N]ammonia and positron emission tomography at baseline and study conclusion.
      RESULTS: After 3 months, HbA(1c) levels dropped by 0.68% in the pioglitazone
      group and increased by 0.17% in the placebo group (P = 0.009 for difference
      between groups). Triglyceride (-93 vs. -39 mg/dl, P = 0.026) and HDL
      concentrations (+4.8 vs. -6.0 mg/dl, P = 0.014) improved significantly in the
      pioglitazone group compared with placebo. Despite these favorable changes, there
      was no demonstrable change in baseline MBF (-0.05 +/- 0.24 vs. -0.09 +/- 0.24 ml
      . min(-1) . g(-1), P = 0.45), adenosine-stimulated MBF (0.10 +/- 0.75 vs. 0.14 +/
      0.31 ml . min(-1) . g(-1), P = 0.25), or coronary flow reserve (0.45 +/- 1.22
      vs. 0.35 +/- 0.72 ml . min(-1) . g(-1), P = 0.64) after 12 weeks of exposure to
      pioglitazone or placebo, respectively. Regression analysis revealed that lower
      glucose concentration at the time of the study was associated with higher
      coronary flow reserve (P = 0.012). CONCLUSIONS: Pioglitazone treatment for 12
      weeks in subjects with insulin-requiring type 2 diabetes had no demonstrable
      effect on coronary flow reserve despite metabolic improvements. Higher ambient
      glucose levels contribute to impaired vascular reactivity in individuals with
      diabetes.

PMID- 15855581
TI  - Reduction in cardiovascular events with atorvastatin in 2,532 patients with type
      2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial--lipid-lowering arm (ASCOT
      LLA).
AB  - OBJECTIVE: This study aims to establish the benefits of lowering cholesterol in
      diabetic patients with well-controlled hypertension and average/below-average
      cholesterol concentrations, but without established coronary disease. RESEARCH
      DESIGN AND METHODS: In the lipid-lowering arm of the Anglo-Scandinavian Cardiac
      Outcomes Trial (ASCOT-LLA), 10,305 hypertensive patients with no history of
      coronary heart disease (CHD) but at least three cardiovascular risk factors were
      randomly assigned to receive 10 mg atorvastatin or placebo. Effects on total
      cardiovascular outcomes in 2,532 patients who had type 2 diabetes at
      randomization were compared. RESULTS: During a median follow-up of 3.3 years,
      concentrations of total and LDL cholesterol among diabetic participants included
      in ASCOT-LLA were approximately 1 mmol/l lower in those allocated atorvastatin
      compared with placebo. There were 116 (9.2%) major cardiovascular events or
      procedures in the atorvastatin group and 151 (11.9%) events in the placebo group
      (hazard ratio 0.77, 95% CI 0.61-0.98; P = 0.036). For the individual components
      of this composite end point, the number of events occurring in the diabetes
      subgroup was small. Therefore, although fewer coronary events (0.84, 0.55-1.29; P
      = 0.14) and strokes (0.67, 0.41-1.09; P = 0.66) were observed among the patients
      allocated atorvastatin, these reductions were not statistically significant.
      CONCLUSIONS: Atorvastatin significantly reduced the risk of major cardiovascular
      events and procedures among diabetic patients with well-controlled hypertension
      and without a history of CHD or markedly elevated cholesterol concentrations. The
      proportional reduction in risk was similar to that among participants who did not
      have diagnosed diabetes. Allocation to atorvastatin prevented approximately 9
      diabetic participants from suffering a first major cardiovascular event or
      procedure for every 1,000 treated for 1 year.

PMID- 15855582
TI  - Incremental predictive value of carotid ultrasonography in the assessment of
      coronary risk in a cohort of asymptomatic type 2 diabetic subjects.
AB  - OBJECTIVE: Consensus guidelines recommend cardiovascular risk assessment as the
      initial step of primary prevention. The aim of this study was to evaluate the
      incremental predictive value for coronary events conferred by carotid
      ultrasonography in addition to risk assessment by Framingham score and screening
      for silent myocardial ischemia in a cohort of type 2 diabetic patients. RESEARCH
      DESIGN AND METHODS: We prospectively studied 229 patients free of any
      cardiovascular complication with at least one additional cardiovascular risk
      factor. At baseline, all patients had an exercise treadmill test, carotid intima
      media thickness (IMT) measurement, and coronary risk assessment by Framingham
      score. Cardiovascular events were registered during a 5-year follow-up period.
      RESULTS: Age, carotid IMT, carotid plaques, number of risk factors, Framingham
      score, and suboptimal exercise electrocardiogram were associated with incident
      cardiovascular events (P < 0.05). Carotid IMT was an independent predictor of
      cardiovascular events (P = 0.045). The predictive value for coronary events was
      similar for carotid IMT and Framingham score as assessed by area under the
      receiver operating characteristic curves. An improvement in risk prediction was
      conferred by addition of carotid IMT in a Cox model (global chi(2) increased from
      14.1 to 18.1, P = 0.035). CONCLUSIONS: This prospective study confirms that
      carotid IMT is a marker of cardiovascular risk in this type 2 diabetic cohort,
      establishes that carotid IMT provides a similar predictive value for coronary
      events than Framingham score, and suggests that the combination of these two
      indexes significantly improves risk prediction for these patients.

PMID- 15855583
TI  - Familial aggregation of severity of diabetic retinopathy in Mexican Americans
      from Starr County, Texas.
AB  - OBJECTIVE: Diabetic retinopathy is a major cause of blindness. To determine
      whether retinopathy itself or only its severity aggregates in families, we
      examined the occurrence and severity of diabetic retinopathy in Mexican-American
      siblings with type 2 diabetes. RESEARCH DESIGN AND METHODS: Using stereoscopic
      fundus photography of seven standard fields, we measured retinopathy in 656 type
      2 diabetic patients from 282 Mexican-American families from Starr County, Texas.
      Retinopathy severity was scored using the Early Treatment of Diabetic Retinopathy
      Study system and classified as no retinopathy, early nonproliferative diabetic
      retinopathy (NPDR-E), moderate-to-severe nonproliferative diabetic retinopathy
      (NPDR-S), or proliferative diabetic retinopathy (PDR). RESULTS: Of 249 siblings
      of randomly selected probands with retinopathy, 169 (67.9%) had retinopathy,
      compared with 95 of 125 siblings of unaffected probands (76.0%; P = 0.11).
      Proband retinopathy class was associated (P = 0.03) with sibling retinopathy
      class, with significant odds ratios (ORs) for NPDR-E versus no retinopathy (OR
      0.57 [95% CI 0.35-0.93]) and PDR versus NPDR-E (2.02 [1.13-3.63]); the contrast
      of NPDR-S versus NPDR-E approached significance (1.78 [0.99-3.20]). With the more
      severe classes (PDR and NPDR-S) combined in one group and the less severe ones
      (none and NPDR-E) in another, more severe proband retinopathy was associated with
      more severe sibling retinopathy (1.72 [1.03-2.88]). CONCLUSIONS: More severe
      diabetic retinopathy showed evidence of familial aggregation, but the occurrence
      of diabetic retinopathy per se did not. The factors involved in the onset of
      diabetic retinopathy may differ from those involved in its progression to more
      severe forms.

PMID- 15855584
TI  - Validation of a novel screening device (NeuroQuick) for quantitative assessment
      of small nerve fiber dysfunction as an early feature of diabetic polyneuropathy.
AB  - OBJECTIVE: To validate a handheld screening device (NeuroQuick) for an early
      detection of diabetic distal symmetric polyneuropathy (DSP) by quantitative
      testing of cold sensation based on the wind chill factor (NeuroQuick threshold
      [NQT]). RESEARCH DESIGN AND METHODS: NQT was measured on the dorsum of the foot
      in 160 healthy subjects as well as 60 and 128 diabetic patients without and with
      DSP, respectively. DSP was diagnosed by a neurological examination, motor and
      sensory nerve conduction velocity, vibration perception threshold, and warm and
      cold thermal perception threshold (TPT) (TPT Medoc). In addition, a C-64 Hz
      tuning fork and TipTherm device were used as screening instruments. RESULTS: In
      the diabetic cohort, NQT correlated significantly with all nerve function tests,
      with the highest correlation coefficients being found on the foot versus Medoc
      warm TPT (r = 0.618, P < 0.001) and cold TPT (r = 0.529, P < 0.001). Among
      patients with DSP, NQT was abnormal, whereas Medoc warm TPT was normal in 34%,
      whereas only 5% showed the opposite constellation (P < 0.05). Likewise, the
      corresponding percentages for Medoc cold TPT were 32 and 11%, for TipTherm 47 and
      2%, and for the tuning fork 29 and 10% (all P < 0.05), whereas no significant
      differences were noted when comparing NQT with peroneal motor nerve conduction
      velocity, sural sensory nerve conduction velocity, and malleolar vibration
      perception threshold. The coefficients of variation for repeated NQT measurements
      in 41 control and 41 diabetic subjects were 20.4 and 8.5%, respectively.
      CONCLUSIONS: The NeuroQuick is a valid and reliable screening tool for
      quantitative assessment of small nerve fiber dysfunction. This device appears to
      be more sensitive in detecting early diabetic polyneuropathy than both elaborate
      thermal testing and screening tests such as the tuning fork.

PMID- 15855585
TI  - Magnesium deficiency is associated with insulin resistance in obese children.
AB  - OBJECTIVE: Magnesium deficiency has been associated with insulin resistance (IR)
      and increased risk for type 2 diabetes in adults. This study was designed to
      determine whether obese children exhibit serum or dietary magnesium deficiency
      and its potential association with IR. RESEARCH DESIGN AND METHODS: We studied 24
      obese nondiabetic children (BMI > or =85th percentile) and 24 sex- and puberty
      matched lean control subjects (BMI <85th percentile). We measured serum
      magnesium, indexes of insulin sensitivity, dietary magnesium intake (using a food
      frequency questionnaire), and body composition (by air displacement
      plethysmography). RESULTS: Serum magnesium was significantly lower in obese
      children (0.748 +/- 0.015 mmol/l, means +/- SE) compared with lean children
      (0.801 +/- 0.012 mmol/l) (P = 0.009). Serum magnesium was inversely correlated
      with fasting insulin (r(s) = -0.36 [95% CI -0.59 to -0.08]; P = 0.011) and
      positively correlated with quantitative insulin sensitivity check index (QUICKI)
      (0.35 [0.06-0.58]; P = 0.015). Dietary magnesium intake was significantly lower
      in obese children (obese: 0.12 +/- 0.004 vs. lean: 0.14 +/- 0.004 mg/kcal; P =
      0.003). Dietary magnesium intake was inversely associated with fasting insulin (
      0.43 [-0.64 to -0.16]; P = 0.002) and directly correlated with QUICKI (0.43 [0.16
      0.64]; P = 0.002). CONCLUSIONS: The association between magnesium deficiency and
      IR is present during childhood. Serum magnesium deficiency in obese children may
      be secondary to decreased dietary magnesium intake. Magnesium supplementation or
      increased intake of magnesium-rich foods may be an important tool in the
      prevention of type 2 diabetes in obese children.

PMID- 15855586
TI  - Glucose intolerance is common in Japanese patients with acute coronary syndrome
      who were not previously diagnosed with diabetes.
AB  - OBJECTIVE: Postprandial hyperglycemia has emerged as a new glycometabolic
      condition associated with an excessive risk for coronary artery disease. We
      therefore attempted to evaluate the frequency of postchallenge hyperglycemia in
      patients with acute coronary syndrome (ACS) who were not previously diagnosed to
      have diabetes and did not have a fasting glucose concentration of > or =7 mmol/l
      or an HbA(1c) level >6.0%. We further correlated the presence of postchallenge
      hyperglycemia with the extent of coronary atherosclerosis. RESEARCH DESIGN AND
      METHODS: In all, 134 consecutive ACS patients who met the above inclusion
      criteria were studied. An oral glucose tolerance test was performed before
      discharge. RESULTS: The mean age, fasting glucose, and HbA(1c) were 60 years,
      5.15 mmol/l, and 5.4%, respectively. Among ACS patients, impaired glucose
      tolerance (IGT) and diabetes were found in 50 (37%) and 13 patients (10%),
      respectively. The homeostasis model assessment for insulin resistance did not
      differ substantially among the normal glucose tolerance (NGT), IGT, and diabetic
      groups. Insulinogenic index, however, was lower and the number of stenosed
      vessels higher in diabetic patients compared with NGT patients. CONCLUSIONS:
      Postchallenge hyperglycemia, caused primarily by impaired initial insulin
      secretion, is commonly found in Japanese ACS patients who have not been
      previously diagnosed with diabetes, and this phenomenon is considered to be
      associated with advanced coronary atherosclerosis. Therefore, the present study
      strongly supports the notion that oral glucose tolerance test assessment of
      postchallenge hyperglycemia is essential to identify any previously undiagnosed
      diabetes cases among Japanese ACS patients.

PMID- 15855587
TI  - Use of the diabetes risk score for opportunistic screening of undiagnosed
      diabetes and impaired glucose tolerance: the IGLOO (Impaired Glucose Tolerance
      and Long-Term Outcomes Observational) study.
AB  - OBJECTIVE: To evaluate an opportunistic screening strategy addressed to
      individuals with one or more cardiovascular risk factor, based on the Diabetes
      Risk Score (DRS) as the initial instrument, for the identification of individuals
      with type 2 diabetes or impaired glucose tolerance (IGT). RESEARCH DESIGN AND
      METHODS: The DRS, a simple self-administered questionnaire, was completed by
      individuals identified by general practitioners and presenting with one or more
      cardiovascular risk factor. All patients underwent a 2-h oral glucose tolerance
      test (OGTT). The optimal DRS cutoff was calculated by applying the receiver
      operating characteristic curve. RESULTS: Overall, 1,377 individuals aged between
      55 and 75 years received an OGTT and completed the DRS. Mean DRS values showed a
      marked variation according to glucose metabolism categories, as follows: 8.7 +/-
      3.0 in normoglycemic individuals, 9.5 +/- 3.1 in individuals with impaired
      fasting glucose, 9.9 +/- 3.3 in individuals with IGT, and 12.0 +/- 3.5 in
      individuals with type 2 diabetes. The receiver-operating characteristic curve
      showed that, with a cutoff of 9, the sensitivity of DRS in detecting individuals
      with glucose abnormalities (type 2 diabetes or IGT) was 77% and the specificity
      45%. The use of the DRS as an initial screening instrument, followed by the
      measurement of fasting blood glucose in individuals with a score > or =9 and by
      the OGTT in individuals with a fasting blood glucose between 5.6 and 6.9 mmol/l,
      would lead to the identification of 83% of the case subjects with type 2 diabetes
      and 57% of the case subjects with IGT, at a cost of an OGTT in 38% of the sample
      and a fasting blood glucose in 64%. CONCLUSIONS: The DRS can represent a valid
      inexpensive instrument for opportunistic screening and a useful alternative to
      indiscriminate fasting blood glucose measurement, not readily available in
      general practice.

PMID- 15855588
TI  - Physical activity energy expenditure predicts progression toward the metabolic
      syndrome independently of aerobic fitness in middle-aged healthy Caucasians: the
      Medical Research Council Ely Study.
AB  - OBJECTIVE: To examine over a period of 5.6 years the prospective associations
      between physical activity energy expenditure (PAEE), aerobic fitness (Vo(2max)),
      obesity, and the progression toward the metabolic syndrome in a population-based
      cohort of middle-aged men and women (n = 605) who were free of the metabolic
      syndrome at baseline. RESEARCH DESIGN AND METHODS: PAEE was measured objectively
      by individually calibrated heart rate against energy expenditure. Vo(2max) was
      predicted from a submaximal exercise stress test. Fat mass and fat-free mass were
      assessed by bio-impedance. A metabolic syndrome score was computed by summing the
      standardized values for obesity, hypertension, hyperglycemia, insulin resistance,
      hypertriglyceridemia, and the inverse level of HDL cholesterol and expressed as a
      continuously distributed outcome. Generalized linear models were used to examine
      the independent prospective associations between PAEE and Vo(2max) and the
      metabolic syndrome score after adjusting for sex, baseline age, smoking,
      socioeconomic status, follow-up time, and baseline phenotypes. RESULTS: PAEE
      predicted progression toward the metabolic syndrome, independent of baseline
      metabolic syndrome, body fat, Vo(2max), and other confounding factors
      (standardized beta = -0.00085, P = 0.046). This association was stronger when
      excluding the adiposity component from the metabolic syndrome (standardized beta
      = -0.0011, P = 0.035). Vo(2max) was not an independent predictor of the metabolic
      syndrome after adjusting for physical activity (standardized beta = 0.00011, P =
      0.93). CONCLUSIONS: PAEE predicts progression toward the metabolic syndrome
      independent of aerobic fitness, obesity, and other confounding factors. This
      finding underscores the importance of physical activity for metabolic disease
      prevention even when an improvement in aerobic fitness is absent.

PMID- 15855589
TI  - High proportions of erectile dysfunction in men with the metabolic syndrome.

PMID- 15855590
TI  - Neonatal Bacille Calmette-Guerin vaccination and type 1 diabetes.

PMID- 15855591
TI  - Early pregnancy insulin resistance and subsequent gestational diabetes mellitus.

PMID- 15855592
TI  - Barriers to physical activity among predominantly low-income African-American
      patients with type 2 diabetes.

PMID- 15855593
TI  - Relationship between C-reactive protein and glucose levels in community-dwelling
      subjects without diabetes: the Hisayama Study.

PMID- 15855594
TI  - Six-month treatment with alendronate in acute Charcot neuroarthropathy: a
      randomized controlled trial.

PMID- 15855595
TI  - Early-onset insulin-resistant diabetes in obese Caucasians has features of
      typical type 2 diabetes, but 3 decades earlier.

PMID- 15855596
TI  - Early signs of cardiovascular disease in youth with obesity and type 2 diabetes.

PMID- 15855597
TI  - Associations between liver histology and severity of the metabolic syndrome in
      subjects with nonalcoholic fatty liver disease.

PMID- 15855598
TI  - Glucose-induced insulin secretion in dyslipidemic and normolipidemic patients
      with normal glucose tolerance.

PMID- 15855599
TI  - Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults.

PMID- 15855600
TI  - Continuous glucose monitoring: roadmap for 21st century diabetes therapy.

PMID- 15855601
TI  - The use of U-500 in patients with extreme insulin resistance.

PMID- 15855602
TI  - Defining and reporting hypoglycemia in diabetes: a report from the American
      Diabetes Association Workgroup on Hypoglycemia.

PMID- 15855603
TI  - The European Association for the Study of Diabetes.

PMID- 15855604
TI  - Self-reported diabetes in Northland, New Zealand.

PMID- 15855605
TI  - Simvastatin, fenofibrate, and rhabdomyolysis.

PMID- 15855606
TI  - An inexpensive method to diagnose incipient diabetic nephropathy in developing
      countries.

PMID- 15855607
TI  - Pregestational diabetes and pregnancy: an Australian experience.

PMID- 15855608
TI  - Performance of glucose dehydrogenase-and glucose oxidase-based blood glucose
      meters at high altitude and low temperature.

PMID- 15855609
TI  - Two-year statin therapy does not alter the progression of intima-media thickness
      in patients with type 2 diabetes without manifest cardio-vascular disease:
      response to Beishuizen et al.

PMID- 15855610
TI  - Prevalence of diabetes in greater Beirut.

PMID- 15855613
TI  - Is atherosclerosis in diabetes and impaired fasting glucose driven by elevated
      ldl cholesterol or by decreased hdl cholesterol?: response to Drexel et al.

PMID- 15855614
TI  - Depressive symptoms, insulin resistance, and risk of diabetes in women at
      midlife: response to Everson-Rose et al.

PMID- 15855615
TI  - Mortality and causes of death in a national sample of diabetic patients in
      Taiwan: response to Tseng.

PMID- 15855618
TI  - Differential reprogramming of somatic cell nuclei after transfer into mouse
      cleavage stage blastomeres.
AB  - Mammalian somatic cell cloning requires factors specific to the oocyte for
      reprogramming to succeed. This does not exclude that reprogramming continues
      during the zygote and cleavage stages. The capacity or role of zygotic and
      cleavage stages to reprogram somatic cell nuclei is difficult to assess due to
      the limited development of somatic cell nuclei transplanted into cytoplasts of
      these stages. Alternatively, tetraploid embryos have been used to study
      reprogramming and can be assessed for their contribution to extra-embryonic
      lineages. When mouse cumulus cell nuclei transgenic for Oct4-green fluorescent
      protein (GFP) were injected into intact two- and four-cell stage blastomeres,
      manipulated embryos developed into blastocysts with expression of Oct4-GFP as
      observed in embryos produced by nuclear transfer into metaphase II oocytes.
      However, only the latter contributed to extra-embryonic tissues in day 10.5
      conceptuses, with the exclusion of the somatic genome in cells originating from
      transfer into blastomeres already at 5.5 days post conception. Somatic nuclei
      transferred into cleavage stage blastomeres reinitiated expression of an
      embyronic-specific transgene, but lacked the extent of reprogramming required for
      contribution to postimplantation development, even when complemented by an
      embryonic genome.

PMID- 15855619
TI  - SH2 domain-mediated activation of an SRC family kinase is not required to
      initiate Ca2+ release at fertilization in mouse eggs.
AB  - SRC family kinases (SFKs) function in initiating Ca2+ release at fertilization in
      several species in the vertebrate evolutionary line, but whether they play a
      similar role in mammalian fertilization has been uncertain. We investigated this
      question by first determining which SFK proteins are expressed in mouse eggs, and
      then measuring Ca2+ release at fertilization in the presence of dominant negative
      inhibitors. FYN and YES proteins were found in mouse eggs, but other SFKs were
      not detected; based on this, we injected mouse eggs with a mixture of FYN and YES
      Src homology 2 (SH2) domains. These SH2 domains were effective inhibitors of Ca2+
      release at fertilization in starfish eggs, but did not inhibit Ca2+ release at
      fertilization in mouse eggs. Thus the mechanism by which sperm initiate Ca2+
      release in mouse eggs does not depend on SH2 domain-mediated activation of an
      SFK. We also tested the small molecule SFK inhibitor SU6656, and found that it
      became compartmentalized in the egg cytoplasm, thus suggesting caution in the use
      of this inhibitor. Our findings indicate that although the initiation of Ca2+
      release at fertilization of mammalian eggs occurs by a pathway that has many
      similarities to that in evolutionarily earlier animal groups, the requirement for
      SH2 domain-mediated activation of an SFK is not conserved.

PMID- 15855620
TI  - Chromosome 18 pairing behavior in human trisomic oocytes. Presence of an extra
      chromosome extends bouquet stage.
AB  - Little is known about the first meiotic prophase stages in the human female
      because these occur during fetal life, and only a few studies have addressed
      aneuploid human oocytes. In this paper, the synaptic process in the meiotic
      prophase in three 47, XX+18 cases is analyzed. A complete study of the dynamics
      of centromeres and telomeres, cohesin core and synapsis development in aneuploid
      female meiosis was performed. Investigation of chromosome dynamics in prophase of
      trisomy 18 oocytes show that these events follow the major patterns seen earlier
      in euploid oocytes. However, there is a significant delay in the resolution of
      bouquet topology which could relate to the presence of a surplus chromosome 18
      axial element in zygotene oocytes. Pachytene oocytes displayed normal synapsis
      among the three chromosome 18s. However, in some oocytes the surplus chromosome
      18 core was aligned to the bivalent 18. As ataxia telangiectasia and Rad3 related
      kinase (ATR) has been described as a marker for late-pairing chromosomes in mice,
      ATR distribution was analyzed in human meiocytes--spermatocytes, euploid oocytes
      and trisomic oocytes. In contrast to the observations made in mice, no
      preferential staining for late-pairing chromosomes was observed in humans. In the
      cases studied, bivalent synapses progressed as in a normal ovary, contrasting
      with the hypothesis that a surplus chromosome can modify pairing of other
      chromosomes.

PMID- 15855621
TI  - Germ cell-specific localization of immunoreactive riboflavin carrier protein in
      the male golden hamster: appearance during spermatogenesis and role in sperm
      function.
AB  - Riboflavin carrier protein (RCP) is a phosphoglycoprotein (37 kDa) that is well
      studied in chicken. An immunologically cross-reacting protein was identified in
      mammals and active immunization of male rats and bonnet monkeys with chicken RCP
      lead to an approximately 80% reduction in fertility. However, the physiological
      mechanism responsible for inhibition of male fertility has not been investigated.
      Moreover, information on the cell type-specific localization and the origin of
      immunoreactive RCP during spermatogenesis is extremely limited. Hence, studies
      were carried out to determine the pattern of expression of immunoreactive RCP
      during spermatogenesis and its role in sperm function in the golden hamster.
      Immunoreactive RCP was germ cell-specific, found to be associated with the
      acrosome-organizing region of early spermatids and showed interesting patterns of
      immunolocalization during late stages of spermiogenesis. Mature spermatozoa
      exhibited acrosome-specific localization, mainly in the peri-acrosomal membrane.
      The immunoreactive protein was undetectable in (non)gonadal somatic cells tested.
      The protein had a molecular mass of 45-55 kDa and was biosynthesized by round
      spermatids. The acrosome-specific localization of immunoreactive RCP was
      unchanged during capacitation, but it was substantially lost during acrosome
      reaction. Functional studies indicated that treatment of spermatozoa with anti
      RCP antibodies did not have any effect on either capacitation or acrosome
      reaction, but markedly reduced the rate of sperm penetration into zona-free
      hamster oocytes. These results show the existence of male germ cell-specific
      immunoreactive RCP, having a potential role in sperm-egg interaction in hamsters.
      Also the pattern of immunoreactive-RCP localization makes it an ideal marker to
      monitor development of acrosome in mammalian spermatozoa.

PMID- 15855622
TI  - Neonatal treatment of rats with diethylstilboestrol (DES) induces stromal
      epithelial abnormalities of the vas deferens and cauda epididymis in adulthood
      following delayed basal cell development.
AB  - This study investigated whether transient, neonatal (days 2-12) treatment of rats
      with the potent oestrogen, diethylstilboestrol (DES), altered the structure of
      the cauda epididymis/vas deferens in adulthood, and if the changes observed
      related to altered development of basal cells in early puberty. Neonatal
      treatment with 10 microg DES resulted in the following during adulthood: (a)
      coiling of the normally straight initial vas deferens, (b) gross epithelial
      abnormalities, (c) 4-fold widening of the periductal non-muscle layer, (d)
      infiltration of immune cells across the epithelium into the lumen, and (e)
      reduction/absence of sperm from the vas deferens lumen. Amongst affected
      animals>75% exhibited reduced epithelial immunoexpression of androgen receptor
      and aberrant oestrogen receptor-alpha immunoexpression and 63% exhibited multi
      layering of basal cells coincident with increased epithelial cell proliferation.
      None of the aforementioned changes occurred in rats treated neonatally with 0.1
      microg DES. As basal cells play a key role in the development of epithelia such
      as that in the epididymis and vas deferens, we went on to investigate if neonatal
      DES treatment affected basal cell development. In controls, basal cells were
      first evident at day 10 (vas deferens) or day 18 (cauda). Rats treated with 10
      microg, but not those treated with 0.1 microg, DES, showed approximately 90%
      reduction (P<0.001) in basal cell numbers at day 15 and day 18. This decrease
      coincided with gross suppression of testosterone levels; co-treatment of rats
      with 10 microg DES+testosterone maintained basal cell numbers at control levels
      at day 18. However, suppression of testosterone production (GnRH antagonist
      treatment) or action (flutamide treatment) did not alter basal cell numbers. It
      is concluded that neonatal exposure to high oestrogen levels coincident with
      reduced testosterone action results in abnormal changes in the adult cauda/vas
      deferens that are preceded by delayed differentiation of basal cells. These
      findings imply a role for androgens and oestrogens in basal cell development and
      suggest that this may be pivotal in determining normal epithelial (and stromal)
      development of the cauda/vas deferens.

PMID- 15855623
TI  - Involvement of CD44 in leukocyte recruitment to the rat testis in experimental
      autoimmune orchitis.
AB  - Experimental autoimmune orchitis (EAO) is characterized by an interstitial
      mononuclear cell infiltrate and a severe lesion of the seminiferous tubules with
      germ cells that undergo apoptosis and sloughing. The aim of this study was to
      determine the role of CD44 in testicular leukocyte recruitment in EAO. The
      biological functions of CD44 have been attributed to the generation of a
      functionally active hyaluronan-binding phenotype. Orchitis was induced in Sprague
      Dawley adult rats by active immunization with an emulsion of testicular
      homogenate and complete Freund's adjuvant using Bordetella pertussis as co
      adjuvant. Control rats (C) injected with saline and adjuvants and normal (N)
      untreated rats were also studied. CD44 expression was analyzed by flow cytometry
      in peripheral blood mononuclear cells (PBMC) and lymph node cells isolated from
      rats at different times after the first immunization. We observed an increase in
      the mean fluorescence intensity of both samples in the C and experimental (E)
      groups only after the immunization period. A significant decrease in percentage
      of CD44+PBMC and in mean fluorescence intensity was observed in rats with
      orchitis compared with the C group. By in vitro hyaluronic acid-binding assay we
      demonstrated that the percentage of PBMC adhesion was higher in the E group
      compared with the C and N groups. By immunohistochemistry, we observed a
      significant increase in the number of CD44+cells in the testicular interstitium
      of rats with severe orchitis compared with the N and C groups. These results
      suggested that the CD44 molecule is involved in the homing of lymphomonocytes
      into the testes of rats with autoimmune orchitis.

PMID- 15855624
TI  - Histological and steroidogenic changes in dominant ovarian follicles during
      oestradiol-induced atresia in heifers.
AB  - Histological and steroidogenic changes within dominant ovarian follicles (DFs)
      undergoing atresia following systemic administration of oestradiol benzoate (ODB)
      were characterized in beef heifers. At 5.6+/-0.1 days after the onset of oestrus,
      heifers received 1 mg ODB i.m./500 kg body weight (ODB; n=15) or served as
      controls (n=15). Timing of treatment initiation was designated as hour (h) 0 on
      day (d) 0, and coincided with the presence of the DF of the first follicular wave
      (DF1). Within treatments, the DF1 was collected following ovariectomy in four
      animals at h 12, h 36 or after ultrasonic detection of a new wave (NW) of ovarian
      follicular development. In heifers of the NW groups (n=7 per treatment), blood
      samples were collected at intervals of 20 min for 12 h beginning at h-12, 0, 24
      and 48 to characterize circulating LH patterns. Administration of ODB suppressed
      (P<0.01) mean concentrations of LH at h 24 and h 48 by preventing (P<0.05) the
      increase in LH pulse amplitude observed in controls, but had no effect on FSH.
      Follicular fluid (FF) concentrations of androgens and oestradiol were reduced at
      h 36 in the ODB-treated group. The diameter of the DF1 and the number of
      granulosa cell layers were also reduced in ODB-treated as compared with control
      heifers. Treatment differences were not observed in the proportion of apoptotic
      granulosa cells as assessed using the TUNEL assay method, and timing of a new
      wave of follicular development (d 4.6+/-0.2) was similar (P>0.1) among
      treatments. A prominent characteristic of oestradiol-induced atresia of the DF1
      of the oestrous cycle in heifers was a loss in oestrogenic function associated
      with reduced LH support. However, the timing of new follicular development may be
      influenced by a factor(s) other than the status of the DF undergoing oestradiol
      induced atresia.

PMID- 15855625
TI  - Alterations in follicular dynamics and steroidogenic abilities induced by heat
      stress during follicular recruitment in goats.
AB  - We investigated the changes in follicular dynamics and steroidogenic activity
      during heat stress in goats. Adult female goats were exposed to heat stress at 36
      degrees C and 70% relative humidity for 48 h and then injected with prostaglandin
      (PG) F2alpha (the time of PGF2alpha injection was designated as 0 h). In
      experiment 1, every follicle greater than 2 mm in diameter was monitored by
      ultrasonography to investigate the follicular dynamics, and plasma concentrations
      of FSH, LH, progesterone, and oestradiol were measured from -48 h to 120 h. In
      experiment 2, the follicles were recovered from the goats at 48 h, and the
      concentration of oestradiol, the aromatase activity, and the LH receptor level in
      the follicles were determined. In control (non-heat-stressed) goats, ovulatory
      follicles were mainly recruited from -24 h to 0 h, whereas no follicles recruited
      during that period were ovulated in the heat-stressed goats. The timing of the
      recruitment of ovulatory follicles was delayed by heat stress by approximately 24
      h. The plasma concentration of oestradiol in the heat-stressed goats was
      significantly lower from 36 to 54 h compared with the controls, although the
      concentrations of FSH and progesterone did not differ between the treatments. In
      addition, the concentration of oestradiol, the aromatase activity, and the LH
      receptor level in the follicles from heat-stressed goats were significantly lower
      compared with the controls. These results indicate that heat stress during
      follicular recruitment suppresses subsequent growth to ovulation, accompanied by
      decreased LH receptor level and oestradiol synthesis activity in the follicles.

PMID- 15855626
TI  - Immunological properties of human decidual macrophages--a possible role in
      intrauterine immunity.
AB  - Our aim was to investigate the contribution of decidual macrophages, which
      constitute an important immune component of the decidua in late gestation, to
      intrauterine defence mechanisms. Using flow cytometry we examined the ability of
      decidual macrophages, isolated from term decidua, to bind and phagocytose
      fluorescence-labelled bacterial and yeast bioparticles. We also assessed their
      ability to generate superoxide radicals and tumour necrosis factor-alpha
      following lipopolysaccharide challenge. Decidual macrophages bound bacterial and
      yeast particles in a dose-dependent manner, which subsequently led to
      phagocytosis. These macrophages also produced superoxide radicals and the pro
      inflammatory cytokine TNF-alpha when challenged with bacterial
      lipopolysaccharides. These results suggest a role for decidual macrophages in
      pathogen recognition and clearance during pregnancy, and, therefore, they are
      likely to protect the fetus against intrauterine infections which might otherwise
      lead to preterm labour.

PMID- 15855627
TI  - Differential expression of mesotocin receptors in the uterus and ovary of the
      pregnant tammar wallaby.
AB  - Mesotocin, an oxytocin-like peptide, is released in highest concentrations during
      parturition in macropodid marsupials. In late pregnant wallabies, uterine
      sensitivity to mesotocin increases markedly in the myometrium of the gravid
      uterus. This coincides with a significant increase in myometrial mesotocin
      receptor concentrations 3-4 days before term. To date, there is no information on
      mesotocin receptor gene expression in female wallaby reproductive tissues. This
      study aimed to examine mesotocin receptor gene expression in the uterus and
      ovaries of pregnant tammar wallabies, and to localise mesotocin receptors within
      the uterus. An RT-PCR strategy produced a consensus nucleotide sequence of 834
      bp, which encoded 278 amino acids of transmembrane domains I to VI. This protein
      sequence has approximately 80% homology with the bovine and rat oxytocin receptor
      exon 2 region. Only one mesotocin receptor was detected in the tammar genome. The
      myometrium and mammary gland both expressed a 4.1 kb mesotocin receptor gene
      transcript. Myometrial mesotocin receptor gene expression increased on day 22 of
      the 26-day gestation and was significantly higher in the gravid than the non
      gravid uterus in late pregnancy. This pattern of mesotocin receptor gene
      expression paralleled mesotocin receptor concentrations. Mesotocin binding sites
      were localised only to the myometrium, the highest densities being observed in
      the gravid uterus. Finally, this study showed high expression of mesotocin
      receptors in the corpus luteum. The pattern of luteal mesotocin receptor
      expression differed from the myometrium, with a decrease in mesotocin receptors
      occurring on the day of expected births.

PMID- 15855628
TI  - Differential expression of the PEA3 subfamily of ETS transcription factors in the
      mouse ovary and peri-implantation uterus.
AB  - The objective of the present investigation was to examine the spatio-temporal
      expression of three members of the ETS family of transcription factors, ERM,
      ER81, and PEA3, in the peri-implantation mouse uterus and in the ovary. These
      three factors belong to the PEA3 subfamily and are known to mediate diverse
      functions ranging from neuronal development to tumor progression. As
      transcription factors, they regulate the expression of a number of genes with
      various biological functions. Since several genes with known roles in the
      reproductive processes have been shown to be under the regulation of one of these
      factors, we sought to investigate the expression of ERM, ER81, and PEA3 in the
      mouse ovary and uterus. Quantitative RT-PCR analyses showed that ERM, ER81, and
      PEA3 were all expressed in the peri-implantation mouse uterus, with higher levels
      of expression on days 4 and 5 of pregnancy. To determine the cell type-specific
      expression of these factors, we employed in situ hybridization, the results of
      which revealed that ERM was expressed in both the epithelium and the stroma on
      days 4 and 5 of pregnancy. Uterine glands showed a high expression of ERM on
      those days. ERM was also highly expressed in the corpora lutea of the mouse
      ovary. Both ER81 and PEA3 were expressed at low levels in the stroma on days 4
      and 5. On day 8, while ERM and PEA3 were mainly expressed in the embryo and were
      at low levels in the maternal decidua in a diffused pattern, ER81 was highly
      expressed in the vascular bed of the mesometrial deciduum. Both ER81 and PEA3
      were undetectable in the mouse ovary. Collectively, these data show that ERM is
      implicated in the early event of implantation as well as in ovarian functions,
      while ER81 is involved in the establishment of the maternal vasculature for
      subsequent placental development. PEA3 is apparently an embryonic factor for
      early embryogenesis.

PMID- 15855629
TI  - Estrous cycle characterisation and artificial insemination using frozen-thawed
      spermatozoa in the bottlenose dolphin (Tursiops truncatus).
AB  - The reproductive endocrinology of the bottlenose dolphin, Tursiops truncatus, was
      characterized to facilitate the development of artificial insemination using
      cryopreserved spermatozoa. Specific objectives were: (i) to determine the
      excretory dynamics of urinary luteinizing hormone (LH) and ovarian steroid
      metabolites during the estrous cycle; (ii) to evaluate the effect of an
      exogenously administered synthetic progesterone analog (altrenogest) on
      reproductive hormone excretion; (iii) to correlate follicular growth and
      ovulation (as determined by transabdominal ultrasound) to urinary LH and ovarian
      steroid metabolites; (iv) examine the in vivo fertilisation capacity of
      cryopreserved semen, and (v) to develop an intrauterine insemination technique.
      Based on urinary endocrine monitoring of natural estrous cycles (2 consecutive
      cycles) and nine post altrenogest cycles in ten females, estrous cycles were
      found to be 36 days long and comprised of an 8 day and 19 day follicular and
      luteal phase, respectively. Peak estrogen conjugates (EC; 5.4+/-3.8 ng/mg
      creatinine (Cr)) occurred 8 h prior to the LH surge (70.9+/-115.7 ng/mg Cr). The
      time of ovulation, as determined by ultrasonography, occurred 32.1+/-8.9 h and
      24.3+/-7.0 h after the onset of the LH surge and LH peak, respectively. Mean
      preovulatory follicular diameter and circumference were 2.1+/-0.5 cm and 6.5+/
      1.5 cm, respectively. Of the 27 estrous synchronisation attempts, 13 resulted in
      an ovulatory cycle, with ovulation occurring 21 days post-altrenogest treatment.
      Intrauterine (4 of 5) and intracornual (1 of 3) inseminations conducted across
      eight estrous cycles resulted in five pregnancies (63%), one pregnancy resulted
      from the use of liquid stored semen, whereas four were achieved using
      cryopreserved semen. These data provide new information on female bottlenose
      dolphin reproductive physiology, and demonstrate that the combination of
      endocrine monitoring and serial ultrasonography contributed to successful AI
      using liquid-stored and cryopreserved semen.

PMID- 15855630
TI  - Fatty acid oxidation in the pathogenesis of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common dementing illness of the elderly and
      is a mounting public health problem. Pharmacoepidemiological data, analytical
      data from human tissue and body fluids, and mechanistic data mostly from murine
      models all have implicated oxidation products of two fatty acids, arachidonic
      acid (AA) and docosahexaenoic acid (DHA), in the pathogenesis of
      neurodegeneration. Here we review the biochemistry of AA and DHA oxidation, both
      enzyme-catalyzed and free radical mediated, and summarize those studies that have
      investigated these oxidation products as effectors of neurodegeneration and
      biomarkers of AD. Given the evolving appreciation for toxicity associated with
      current pharmaceuticals used to block AA and DHA oxidation, we close by
      speculating on likely areas of future research directed at suppressing this facet
      of neurodegeneration. If successful, these interventions are unlikely to cure AD,
      but may check its explosive growth and hopefully reduce its incidence and
      prevalence in the elderly.

PMID- 15855631
TI  - New insights into the tumor metastatic process revealed by gene expression
      profiling.

PMID- 15855632
TI  - Implication of Wt1 in the pathogenesis of nephrogenic failure in a mouse model of
      retinoic acid-induced caudal regression syndrome.
AB  - Renal malformations are common human birth defects that sometimes occur in the
      context of the caudal regression syndrome. Here, we found that exposure of
      pregnant mice to all-trans retinoic acid, at a time when the metanephros has yet
      to form, causes a failure of kidney development along with caudal regression.
      Maternal treatment with Am580 (retinoic acid receptor alpha agonist) also induced
      similar patterns of kidney maldevelopment in the fetus. In metanephroi from
      retinoic acid-treated pregnancies, renal mesenchyme condensed around the ureteric
      bud but then failed to differentiate into nephrons, instead undergoing involution
      by fulminant apoptosis to produce a renal agenesis phenotype. Results of whole
      organ cultures in serum-free medium, and also tissue recombination experiments,
      showed that the nephrogenic defect was intrinsic to the kidney and that it
      resided in the metanephric mesenchyme and not the ureteric bud. Renal mesenchyme
      from control embryos expressed Wilms' tumor 1 (Wt1), but this transcription
      factor, which is indispensable for kidney development, failed to express in
      metanephroi of retinoic acid-exposed embryos. Wt1 expression and organogenesis
      were both restored, however, when metanephroi from retinoic acid-treated
      pregnancies were grown in serum-containing media. Our data illuminate the
      pathobiology of a severe, teratogen-induced kidney malformation.

PMID- 15855633
TI  - In response to protein load podocytes reorganize cytoskeleton and modulate
      endothelin-1 gene: implication for permselective dysfunction of chronic
      nephropathies.
AB  - Effacement of podocyte foot processes occurs in many proteinuric nephropathies
      and is accompanied by rearrangement of the actin cytoskeleton. Here, we studied
      whether protein overload affects intracellular pathways, leading to cytoskeletal
      architecture changes and ultimately to podocyte dysfunction. Mouse podocytes
      bound and endocytosed both albumin and IgG via receptor-specific mechanisms.
      Protein overload caused redistribution of F-actin fibers instrumental to up
      regulation of the prepro-endothelin (ET)-1 gene and production of the
      corresponding peptide. Increased DNA-binding activity for nuclear factor (NF)
      kappaB and Ap-1 nuclear proteins was measured in nuclear extracts of podocytes
      exposed to excess proteins. Both Y27632, which inhibits Rho kinase-dependent
      stress fiber formation, and jasplakinolide, an F-actin stabilizer, decreased NF
      kappaB and Ap-1 activity and reduced ET-1 expression. This suggested a role for
      the cytoskeleton, through activated Rho, in the regulation of the ET-1 peptide.
      Focal adhesion kinase (FAK), an integrin-associated nonreceptor tyrosine kinase,
      was phosphorylated by albumin treatment via Rho kinase-triggered actin
      reorganization. FAK activation led to NF-kappaB- and Ap-1-dependent ET-1
      expression. These data suggest that reorganization of the actin cytoskeletal
      network in response to protein load is implicated in modulation of the ET-1 gene
      via Rho kinase-dependent FAK activation of NF-kappaB and Ap-1 in differentiated
      podocytes. Increased ET-1 generation might alter glomerular permselectivity and
      amplify the noxious effect of protein overload on dysfunctional podocytes.

PMID- 15855635
TI  - A prostacyclin analog prevents radiocontrast nephropathy via phosphorylation of
      cyclic AMP response element binding protein.
AB  - We reported previously that radiocontrast medium induces caspase-dependent
      apoptosis and that cAMP analogs inhibit cell injury in cultured renal tubular
      cells. In the present study, cellular mechanisms underlying the protective
      effects of cAMP were determined. Ioversol, a radiocontrast medium, caused cell
      injury accompanied by decreases in Bcl-2, increases in Bax, and caspase
      activation in LLC-PK1 cells. Both cell injury and cellular events induced by
      ioversol were inhibited by dibutyryl cAMP and the prostacyclin analog beraprost.
      Dibutyryl cAMP increased phosphorylation of Akt and CREB, both of which were
      reversed by H89, wortmannin and the Akt inhibitor SH-6. The protective effect of
      dibutyryl cAMP was also reversed by these kinase inhibitors. In dominant-negative
      CREB-transfected cells, dibutyryl cAMP no longer prevented cell injury or
      inhibited changes in mRNA expression of Bcl-2 and Bax. In mice with unilateral
      renal occlusion, ioversol increased urinary excretion of N-acetyl-beta-d
      glucosaminidase with concomitant decreases in Bcl-2 mRNA, increases in Bax mRNA,
      activation of caspase-3, and induction of apoptosis in tubular and interstitial
      cells. Beraprost completely reversed these in vivo effects of ioversol. These
      findings suggest that elevation of endogenous cAMP effectively prevents
      radiocontrast nephropathy through activation of A kinase/PI 3-kinase/Akt followed
      by CREB phosphorylation and enhanced expression of Bcl-2.

PMID- 15855634
TI  - Induction of epithelial-mesenchymal transition in alveolar epithelial cells by
      transforming growth factor-beta1: potential role in idiopathic pulmonary
      fibrosis.
AB  - The hallmark of idiopathic pulmonary fibrosis (IPF) is the myofibroblast, the
      cellular origin of which in the lung is unknown. We hypothesized that alveolar
      epithelial cells (AECs) may serve as a source of myofibroblasts through
      epithelial-mesenchymal transition (EMT). Effects of chronic exposure to
      transforming growth factor (TGF)-beta1 on the phenotype of isolated rat AECs in
      primary culture and a rat type II cell line (RLE-6TN) were evaluated.
      Additionally, tissue samples from patients with IPF were evaluated for cells co
      expressing epithelial (thyroid transcription factor (TTF)-1 and pro-surfactant
      protein-B (pro-SP-B), and mesenchymal (alpha-smooth muscle actin (alpha-SMA))
      markers. RLE-6TN cells exposed to TGF-beta1 for 6 days demonstrated increased
      expression of mesenchymal cell markers and a fibroblast-like morphology, an
      effect augmented by tumor necrosis factor-alpha (TNF-alpha). Exposure of rat AECs
      to TGF-beta1 (100 pmol/L) resulted in increased expression of alpha-SMA, type I
      collagen, vimentin, and desmin, with concurrent transition to a fibroblast-like
      morphology and decreased expression of TTF-1, aquaporin-5 (AQP5), zonula
      occludens-1 (ZO-1), and cytokeratins. Cells co-expressing epithelial markers and
      alpha-SMA were abundant in lung tissue from IPF patients. These results suggest
      that AECs undergo EMT when chronically exposed to TGF-beta1, raising the
      possibility that epithelial cells may serve as a novel source of myofibroblasts
      in IPF.

PMID- 15855636
TI  - Regulation of alpha-smooth muscle actin expression in granulation tissue
      myofibroblasts is dependent on the intronic CArG element and the transforming
      growth factor-beta1 control element.
AB  - Myofibroblasts are specialized contractile fibroblasts that are critical in wound
      closure and tissue contracture. Generation of contractile force is correlated
      with the expression of alpha-smooth muscle actin (alpha-SMA); however, little is
      known regarding molecular mechanisms that control activation of alpha-SMA in
      myofibroblasts in granulation tissue. The aims of the present studies were to
      identify sufficient promoter regions required for alpha-SMA expression in
      myofibroblasts in vivo and to determine whether activation of alpha-SMA
      expression in myofibroblasts in vivo is dependent on an intronic CArG
      [CC(A/T)6GG] and a transforming growth factor-beta1 control element (TCE) that
      are required for alpha-SMA expression in smooth muscle cells. A Lac Z transgene
      construct from -2600 through the first intron was expressed in myofibroblasts
      within granulation tissue of cutaneous wounds in a pattern that closely mimicked
      endogenous alpha-SMA expression. Mutation of either the intronic CArG element or
      the TCE completely inhibited transgene expression in myofibroblasts in
      granulation tissue and responsiveness to transforming growth factor-beta1 in
      cultured transgenic fibroblasts. These same elements were also critical in
      regulating alpha-SMA expression during skeletal muscle repair but not during
      skeletal muscle development. Taken together, these results provide the first in
      vivo evidence for the importance of the intronic CArG and TCE cis-elements in the
      regulation of alpha-SMA expression in myofibroblasts in granulation tissue.

PMID- 15855637
TI  - Absence of proteinase-activated receptor-1 signaling affords protection from
      bleomycin-induced lung inflammation and fibrosis.
AB  - Activation of the coagulation cascade is commonly observed in the lungs of
      patients with both acute and chronic inflammatory and fibrotic lung disorders, as
      well as in animal models of these disorders. The aim of this study was to examine
      the contribution of the major thrombin receptor, proteinase-activated receptor-1
      (PAR-1), during the acute inflammatory and chronic fibrotic phases of lung injury
      induced by intratracheal instillation of bleomycin in mice. Inflammatory cell
      recruitment and increases in bronchoalveolar lavage fluid (BALF) protein were
      attenuated by 56 +/- 10% (P < 0.05) and 53 +/- 12% (P < 0.05), respectively, in
      PAR-1-deficient (PAR-1-/-) mice compared with wild-type (WT) mice. PAR-1-/- mice
      were also protected from bleomycin-induced pulmonary fibrosis with total lung
      collagen accumulation reduced by 59 +/- 5% (P < 0.05). The protection afforded by
      PAR-1 deficiency was accompanied by significant reductions in pulmonary levels of
      the potent PAR-1-inducible proinflammatory and profibrotic mediators, monocyte
      chemoattractant protein-1 (MCP-1), transforming growth factor-beta-1 (TGF-beta1),
      and connective tissue growth factor/fibroblast-inducible secreted protein-12
      (CTGF/FISP12). In addition, PAR-1 was highly expressed in inflammatory and
      fibroproliferative lesions in lung sections obtained from patients with fibrotic
      lung disease. These data show for the first time that PAR-1 signaling plays a key
      role in experimentally induced lung injury, and they further identify PAR-1 as
      one of the critical receptors involved in orchestrating the interplay between
      coagulation, inflammation, and remodeling in response to tissue injury.

PMID- 15855638
TI  - Spontaneous corneal hem- and lymphangiogenesis in mice with destrin-mutation
      depend on VEGFR3 signaling.
AB  - Lymphangiogenesis, the formation of new lymphatic vessels, is important for tumor
      metastasis and induction of immunity to peripheral antigens including organ
      transplants. We herein describe a novel mouse model of spontaneous, secondary
      lymphangiogenesis in the normally avascular cornea. corn1 mice, which suffer from
      a deletion in the gene encoding the cytoskeletal protein destrin, develop
      hemangiogenesis as well as spontaneous outgrowth of LYVE-1+++/CD31+ lymphatic
      vessels into the cornea starting at age 4 weeks. Corneal lymphangiogenesis is
      delayed in onset, is less intense, and regresses earlier compared with
      hemangiogenesis. Moreover, the lymphangiogenesis is preceded only by a mild
      recruitment of CD45+ inflammatory cells into the cornea. In contrast to mice with
      inflammation-induced hem- and lymphangiogenesis, corn1 mice do not develop
      breakdown of the blood-aqueous barrier. Finally, in this novel mouse model, a
      blocking anti-VEGFR3 antibody significantly inhibited not only lymph- but also
      hemangiogenesis. In summary, destrin deletion has differential effects on
      spontaneous hem- and lymphangiogenesis in the normally avascular cornea and
      represents a novel mouse model to study the mechanisms of lymphangiogenesis and
      to test the antihem- and antilymphangiogenic properties of known or new
      antiangiogenic agents.

PMID- 15855639
TI  - SCF(beta-TrCP1) controls Smad4 protein stability in pancreatic cancer cells.
AB  - Smad4, also known as deleted in pancreatic carcinoma locus 4 (DPC4), is a
      critical co-factor in signal transduction pathways activated by transforming
      growth factor (TGF)-beta-related ligands that regulate cell growth and
      differentiation. Mutations in Smad4/DPC4 have been identified in approximately
      50% of pancreatic adenocarcinomas. Here we report that SCF(beta-TrCP1), a
      ubiquitin (E3) ligase, is a critical determinant for Smad4 protein degradation in
      pancreatic cancer cells. We found that F-box protein beta-TrCP1 in this E3 ligase
      interacted with Smad4 and that SCF(beta-TrCP1) inhibited TGF-beta biological
      activity in pancreatic cancer cells by decreasing Smad4 stability. Very low Smad4
      protein levels in human pancreatic ductal adenocarcinoma cells were observed by
      immunohistochemistry. By analyzing pancreatic tumor-derived Smad4 mutants, we
      found that most point-mutated Smad4 proteins, except those within or very close
      to a mutation cluster region, exhibited higher interaction affinity with beta
      TrCP1 and significantly elevated protein ubiquitination by SCF(beta-TrCP1).
      Furthermore, AsPC-1 and Caco-2, two cancer cell lines harboring Smad4 point
      mutations, exhibited rapid Smad4 protein degradation due to the effect of
      SCF(beta-TrCP1). Both Smad4 levels and TGF-beta signaling were elevated by
      retrovirus-delivered beta-TrCP1 siRNA in pancreatic cancer cells. Therefore,
      inhibition of Smad4-specific E3 ligase might be a target for therapeutic
      intervention in pancreatic cancer.

PMID- 15855640
TI  - Therapeutic effect of topical administration of SN50, an inhibitor of nuclear
      factor-kappaB, in treatment of corneal alkali burns in mice.
AB  - We evaluated the therapeutic efficacy of topical administration of SN50, an
      inhibitor of nuclear factor-kappaB, in a corneal alkali burn model in mice. An
      alkali burn was produced with 1 N NaOH in the cornea of C57BL/6 mice under
      general anesthesia. SN50 (10 microg/microl) or vehicle was topically administered
      daily for up to 12 days. The eyes were processed for histological or
      immunohistochemical examination after bromodeoxyuridine labeling or for semi
      quantification of cytokine mRNA. Topical SN50 suppressed nuclear factor-kappaB
      activation in local cells and reduced the incidence of epithelial
      defects/ulceration in healing corneas. Myofibroblast generation, macrophage
      invasion, activity of matrix metalloproteinases, basement membrane destruction,
      and expression of cytokines were all decreased in treated corneas compared with
      controls. To elucidate the role of tumor necrosis factor (TNF)-alpha in
      epithelial cell proliferation, we performed organ culture of mouse eyes with TNF
      alpha, SN50, or an inhibitor of c-Jun N-terminal kinase (JNK) and examined cell
      proliferation in healing corneal epithelium in TNF-alpha-/- mice treated with
      SN50. An acceleration of epithelial cell proliferation by SN50 treatment was
      found to depend on TNF-alpha/JNK signaling. In conclusion, topical application of
      SN50 is effective in treating corneal alkali burns in mice.

PMID- 15855641
TI  - Expression of Smad7 in mouse eyes accelerates healing of corneal tissue after
      exposure to alkali.
AB  - Damage to the cornea from chemical burns is a serious clinical problem that often
      leads to permanent visual impairment. Because transforming growth factor (TGF)
      beta has been implicated in the response to corneal injury, we evaluated the
      effects of altered TGF-beta signaling in a corneal alkali burn model using mice
      treated topically with an adenovirus (Ad) expressing inhibitory Smad7 and mice
      with a targeted deletion of the TGF-beta/activin signaling mediator Smad3.
      Expression of exogenous Smad7 in burned corneal tissue resulted in reduced
      activation of Smad signaling and nuclear factor-kappaB signaling via RelA/p65.
      Resurfacing of the burned cornea by conjunctival epithelium and its
      differentiation to cornea-like epithelium were both accelerated in Smad7-Ad
      treated corneas with suppressed stromal ulceration, opacification, and
      neovascularization 20 days after injury. Introduction of the Smad7 gene
      suppressed invasion of monocytes/macrophages and expression of
      monocyte/macrophage chemotactic protein-1, TGF-beta1, TGF-beta2, vascular
      endothelial growth factor, matrix metalloproteinase-9, and tissue inhibitors of
      metalloproteinase-2 and abolished the generation of myofibroblasts. Although
      acceleration of healing of the burned cornea was also observed in mice lacking
      Smad3, the effects on epithelial and stromal healing were less pronounced than
      those in corneas treated with Smad7. Together these data suggest that
      overexpression of Smad7 may have effects beyond those of simply blocking
      Smad3/TGF-beta signaling and may represent an effective new strategy for
      treatment of ocular burns.

PMID- 15855642
TI  - Lethal encephalitis in myeloid differentiation factor 88-deficient mice infected
      with herpes simplex virus 1.
AB  - Herpes simplex virus 1 (HSV-1), a large DNA virus from the Herpesviridae family,
      is the major cause of sporadic lethal encephalitis and blindness in humans.
      Recent studies have shown the importance of Toll-like receptors (TLRs) in the
      immune response to HSV-1 infection. Myeloid differentiation factor 88 (MyD88) is
      a critical adaptor protein that is downstream to mediated TLR activation and is
      essential for the production of inflammatory cytokines. Here, we studied the
      relationship between MyD88 and HSV-1 using a purified HSV-1 isolated from a
      natural oral recurrent human infection. We observed the activation of TLR-2 by
      HSV-1 in vitro using Chinese hamster ovary cells stably transfected with a
      reporter gene. Interestingly, we found that only peritoneal macrophages from
      MyD88-/- mice, but not macrophages from TRL2-/- or from wild-type mice, were
      unable to produce tumor necrosis factor-alpha in response to HSV-1 exposure.
      Additionally, although TLR2-/- mice showed no enhanced susceptibility to
      intranasal infection with HSV-1, MyD88-/- mice were highly susceptible to
      infection and displayed viral migration to the brain, severe neuropathological
      signs of encephalitis, and 100% mortality by day 10 after infection. Together,
      our results suggest that innate resistance to HSV-1 is mediated by MyD88 and may
      rely on activation of multiple TLRs.

PMID- 15855643
TI  - Kinetics of disease progression and host response in a rat model of bubonic
      plague.
AB  - Plague, caused by the gram-negative bacterium Yersinia pestis, primarily affects
      rodents but is also an important zoonotic disease of humans. Bubonic plague in
      humans follows transmission by infected fleas and is characterized by an acute,
      necrotizing lymphadenitis in the regional lymph nodes that drain the intradermal
      flea bite site. Septicemia rapidly follows with spread to spleen, liver, and
      other organs. We developed a model of bubonic plague using the inbred Brown
      Norway strain of Rattus norvegicus to characterize the progression and kinetics
      of infection and the host immune response after intradermal inoculation of Y.
      pestis. The clinical signs and pathology in the rat closely resembled
      descriptions of human bubonic plague. The bacteriology; histopathology; host
      cellular response in infected lymph nodes, blood, and spleen; and serum cytokine
      levels were analyzed at various times after infection to determine the kinetics
      and route of disease progression and to evaluate hypothesized Y. pestis
      pathogenic mechanisms. Understanding disease progression in this rat infection
      model should facilitate further investigations into the molecular pathogenesis of
      bubonic plague and the immune response to Y. pestis at different stages of the
      disease.

PMID- 15855644
TI  - Complementary contribution of CD4 and CD8 T lymphocytes to T-cell infiltration of
      the intact and the degenerative spinal cord.
AB  - The central role of T cells in inflammatory reactions of the central nervous
      system (CNS) is well documented. However, there is little information about the
      few T cells found within the noninflamed CNS. In particular, the contribution of
      CD4+ and CD8+ T cells to the lymphocyte pool infiltrating the intact CNS, the
      location of these cells in CNS white and gray matter, and changes in the cellular
      composition of T-cell infiltrates coinciding with degeneration are primarily
      undefined. To address these points, we studied T cells in the intact and
      degenerative rat spinal cord. In the intact spinal cord, T cells were
      preferentially located within the gray matter. CD8+ T cells were more numerous
      than CD4+ lymphocytes. In cases of neuroaxonal degeneration or myelin
      degeneration/oligodendrocyte death, T cells were predominantly seen in areas of
      degeneration and were present in increased numbers. These effects were more
      pronounced for the CD4+ than for the CD8+ T-cell subset. Collectively, these data
      provide evidence for a clear cellular and compartmental bias in T-cell
      infiltration of the intact and degenerative spinal cord. This could indicate that
      CD4+ and CD8+ T cells might fulfill complementary roles in the intact and the
      diseased organ.

PMID- 15855645
TI  - Constitutive thrombospondin-1 overexpression contributes to autocrine
      transforming growth factor-beta signaling in cultured scleroderma fibroblasts.
AB  - The extracellular matrix (ECM) glycoprotein thrombospondin-1 (TSP-1) has been
      reported to activate the latent complex of transforming growth factor-beta (TGF
      beta), the major effects of which in mesenchymal cells is stimulation of the
      synthesis of ECM. Previous reports suggested the involvement of an autocrine TGF
      beta loop in the pathogenesis of scleroderma. In this study, we examined whether
      TSP-1 plays a role in maintaining the autocrine TGF-beta loop in scleroderma. TSP
      1 expression was increased in scleroderma patients compared with in healthy
      controls in vivo and in vitro. TGF-beta blocking antibody or TGF-beta1 antisense
      oligonucleotide markedly reduced the up-regulated TSP-1 expression in scleroderma
      fibroblasts but had little effect on normal fibroblasts. The expression of TSP-1
      is up-regulated in scleroderma fibroblasts, possibly at the post-transcriptional
      level just like in normal fibroblasts stimulated with exogenous TGF-beta1. TSP-1
      blocking peptide or antisense oligonucleotide had an inhibitory effect on the up
      regulated alpha2I collagen and phosopho-Smad3 levels in scleroderma fibroblasts
      but had little effects on normal fibroblasts. The transient overexpression of TSP
      1 up-regulated alpha2I collagen and phospho-Smad3 levels in normal fibroblasts
      but had no major effect on scleroderma fibroblasts. Furthermore, these effects of
      transiently overexpressed TSP-1, which possibly occurred via the activation of
      latent TGF-beta1, were abolished by the TGF-beta1 antisense oligonucleotide.
      These results indicate that the constitutive overexpression of TSP-1 may play an
      important role in autocrine TGF-beta signaling and accumulation of ECM in
      scleroderma fibroblasts.

PMID- 15855646
TI  - Matrix metalloproteinase dysregulation in the stria vascularis of mice with
      Alport syndrome: implications for capillary basement membrane pathology.
AB  - Alport syndrome results from mutations in genes encoding collagen alpha3(IV),
      alpha4(IV), or alpha5(IV) and is characterized by progressive glomerular disease
      associated with a high-frequency sensorineural hearing loss. Earlier studies of a
      gene knockout mouse model for Alport syndrome noted thickening of strial
      capillary basement membranes in the cochlea, suggesting that the stria vascularis
      is the primary site of cochlear pathogenesis. Here we combine a novel cochlear
      microdissection technique with molecular analyses to illustrate significant
      quantitative alterations in strial expression of mRNAs encoding matrix
      metalloproteinases-2, -9, -12, and -14. Gelatin zymography of extracts from the
      stria vascularis confirmed these findings. Treatment of Alport mice with a small
      molecule inhibitor of these matrix metalloproteinases exacerbated strial
      capillary basement membrane thickening, demonstrating that alterations in
      basement membrane metabolism result in matrix accumulation in the strial
      capillary basement membranes. This is the first demonstration of true
      quantitative analysis of specific mRNAs for matrix metalloproteinases in a
      cochlear microcompartment. Further, these data suggest that the altered basement
      membrane composition in Alport stria influences the expression of genes involved
      in basement membrane metabolism.

PMID- 15855647
TI  - Overexpression of monocyte chemotactic protein-1/CCL2 in beta-amyloid precursor
      protein transgenic mice show accelerated diffuse beta-amyloid deposition.
AB  - Microglia accumulation at the site of amyloid plaques is a strong indication that
      microglia play a major role in Alzheimer's disease pathogenesis. However, how
      microglia affect amyloid-beta peptide (Abeta) deposition remains poorly
      understood. To address this question, we developed a novel bigenic mouse that
      overexpresses both amyloid precursor protein (APP) and monocyte chemotactic
      protein-1 (MCP-1; CCL2 in systematic nomenclature). CCL2 expression, driven by
      the glial fibrillary acidic protein promoter, induced mononuclear phagocyte (MP;
      monocyte-derived macrophage and microglial) accumulation in the brain. When
      APP/CCL2 transgenic mice were compared to APP mice, a fivefold increase in Abeta
      deposition was present despite increased MP accumulation around hippocampal and
      cortical amyloid plaques. Levels of full-length APP, its C-terminal fragment, and
      Abeta-degrading enzymes (insulin-degrading enzyme and neprilysin) in APP/CCL2 and
      APP mice were indistinguishable. Sodium dodecyl sulfate-insoluble Abeta (an
      indicator of fibrillar Abeta) was increased in APP/CCL2 mice at 5 months of age.
      Apolipoprotein E, which enhances Abeta deposition, was also increased (2.2-fold)
      in aged APP/CCL2 as compared to APP mice. We propose that although CCL2
      stimulates MP accumulation, it increases Abeta deposition by reducing Abeta
      clearance through increased apolipoprotein E expression. Understanding the
      mechanisms underlying these events could be used to modulate microglial function
      in Alzheimer's disease and positively affect disease outcomes.

PMID- 15855648
TI  - Central nervous system injury triggers hepatic CC and CXC chemokine expression
      that is associated with leukocyte mobilization and recruitment to both the
      central nervous system and the liver.
AB  - The administration of interleukin-1beta to the brain induces hepatic CXC
      chemokine synthesis, which increases neutrophil levels in the blood, liver, and
      brain. We now show that such hepatic response is not restricted to the CXC
      chemokines. CCL-2, a CC chemokine, was released by the liver in response to a
      tumor necrosis factor (TNF)-alpha challenge to the brain and boosted monocyte
      levels. Furthermore, a clinically relevant compression injury to the spinal cord
      triggered hepatic chemokine expression of both types. After a spinal cord injury,
      elevated CCL-2 and CXCL-1 mRNA and protein were observed in the liver by TaqMan
      reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent
      assay as early as 2 to 4 hours. Simultaneously, we observed elevated levels of
      these chemokines and circulating leukocyte populations in the blood. Leukocytes
      were recruited to the liver at this early stage, whereas at the site of challenge
      in the central nervous system, few were observed until 24 hours. Artificial
      elevation of blood CCL-2 triggered dose-dependent monocyte mobilization in the
      blood and enhanced monocyte recruitment to the brain after TNF-alpha challenge.
      Attenuation of hepatic CCL-2 production with corticosteroids resulted in reduced
      monocyte levels after the TNF-alpha challenge. Thus, combined production of CC
      and CXC hepatic chemokines appears to amplify the central nervous system response
      to injury.

PMID- 15855649
TI  - Fragmentation of the Golgi apparatus induced by the overexpression of wild-type
      and mutant human tau forms in neurons.
AB  - Tau is a microtubule-associated protein enriched in the axonal compartment. In
      several neurodegenerative diseases including Alzheimer's disease,
      hyperphosphorylated tau accumulates in the somatodendritic compartment, self
      aggregates, and forms neurofibrillary tangles. A fragmentation of the neuronal
      Golgi apparatus (GA) was also observed in Alzheimer's disease. In the present
      study, we examined the effect of overexpressing human tau on the organization of
      the neuronal GA in rat hippocampal cultures and in JNPL3 mice expressing tau
      mutant P301L. GA fragmentation was noted in a significantly higher percentage of
      hippocampal neurons overexpressing wild-type human tau than in control neurons
      over-expressing green fluorescent protein (GFP) alone. Most importantly, in
      neurons overexpressing mutant forms of human tau (P301L, V337M, or R406W), the
      percentage of neurons with a fragmented GA was 10% higher than that of neurons
      overexpressing wild-type human tau. In JNPL3 mice, a significantly higher
      percentage of motor neurons presented a fragmented GA compared to control mice.
      Interestingly, fragmentation of the GA was more frequent in neurons containing an
      accumulation and aggregation of hyperphosphorylated tau in the cell body than in
      neurons without these features. In both primary hippocampal neurons and JNPL3
      mice, the tau-induced GA fragmentation was not caused by apoptosis. The pre-sent
      results implicate tau in GA fragmentation and show that this event occurs before
      the formation of neurofibrillary tangles.

PMID- 15855650
TI  - Platelet-activating factor regulates cadherin-catenin adhesion system expression
      and beta-catenin phosphorylation during Kaposi's sarcoma cell motility.
AB  - In the present study, we evaluated whether motility of Kaposi's sarcoma (KS)
      cells induced by platelet-activating factor (PAF) is dependent on the regulation
      of adherens junctions components. The results obtained indicate that PAF dose and
      time dependently reduced the endogenous expression of the main components of the
      adherens junctions: VE-cadherin, alpha-catenin, and beta-catenin. In addition,
      PAF initiated events that directly or indirectly up-regulated both the tyrosine
      and serine/threonine phosphorylation pathways, and both types of phosphorylation
      of beta-catenin were involved in the motility of KS cells. This motility was
      abrogated by addition of the tyrosine kinase inhibitor genistein, suggesting that
      this phosphorylation is an important signal responsible for breaking down the
      adherens junctions and diminishing the ability of neighboring cells to interact.
      Furthermore, immunofluorescence analysis showed that beta-catenin and VE-cadherin
      staining changed from a uniform distribution along the membrane of controls to a
      diffuse pattern with gap formation in PAF-treated KS cells. In conclusion, the
      data presented here indicate that PAF induces tumor cell motility by altering
      cell-cell adhesion through beta-catenin phosphorylation.

PMID- 15855651
TI  - Deletion of Bid impedes cell proliferation and hepatic carcinogenesis.
AB  - Mechanisms that control the proliferation capability of the initiated cells
      during hepatocarcinogenesis are still largely unclear. We investigated the role
      of a pro-death Bcl-2 family protein, Bid, in liver tumor development using a
      neonatal diethylnitrosamine model. Diethylnitrosamine was administrated to 15-day
      old wild-type and bid-null mice. The development of microfoci at the early stage
      and of gross tumors at the later stage was compared between the two groups of
      mice. Both microfoci and gross tumor development were significantly retarded in
      the bid-null mice, despite reduced cell death as measured by TUNEL staining.
      Further studies indicated that there were significantly less proliferating cells
      in diethylnitrosamine-treated bid-null livers. The regulation of cell
      proliferation by Bid was confirmed in two other systems not involving
      carcinogenesis. Hepatocyte proliferation following partial hepatectomy and T
      lymphocyte proliferation following anti-CD3 stimulation were both retarded in bid
      null mice. Thus, these studies revealed a previously undisclosed function of Bid
      in regulating cell proliferation, which can be important to tumor development.
      Furthermore, the role of Bid in promoting hepatocarcinogenesis is in contrast to
      its reported role in suppressing myeloid leukemia and thus suggests an organ-
      and/or etiology-specific role of the Bcl-2 family proteins in regulating
      oncogenesis.

PMID- 15855652
TI  - Molecular genetic evidence for a common clonal origin of urinary bladder small
      cell carcinoma and coexisting urothelial carcinoma.
AB  - In most cases, small-cell carcinoma of the urinary bladder is admixed with other
      histological types of bladder carcinoma. To understand the pathogenetic
      relationship between the two tumor types, we analyzed histologically distinct
      tumor cell populations from the same patient for loss of heterozygosity (LOH) and
      X chromosome inactivation (in female patients). We examined five polymorphic
      microsatellite markers located on chromosome 3p25-26 (D3S3050), chromosome 9p21
      (IFNA and D9S171), chromosome 9q32-33 (D9S177), and chromosome 17p13 (TP53) in 20
      patients with small-cell carcinoma of the urinary bladder and concurrent
      urothelial carcinoma. DNA samples were prepared from formalin-fixed, paraffin
      embedded tissue sections using laser-assisted microdissection. A nearly identical
      pattern of allelic loss was observed in the two tumor types in all cases, with an
      overall frequency of allelic loss of 90% (18 of 20 cases). Three patients showed
      different allelic loss patterns in the two tumor types at a single locus;
      however, the LOH patterns at the remaining loci were identical. Similarly, the
      same pattern of nonrandom X chromosome inactivation was present in both carcinoma
      components in the four cases analyzed. Concordant genetic alterations and X
      chromosome inactivation between small-cell carcinoma and coexisting urothelial
      carcinoma suggest that both tumor components originate from the same cells in the
      urothelium.

PMID- 15855653
TI  - Up-regulated expression of zonula occludens protein-1 in human melanoma
      associates with N-cadherin and contributes to invasion and adhesion.
AB  - During the process of malignant transformation, nascent melanoma cells escape
      keratinocyte control through down-regulation of E-cadherin and instead
      communicate among themselves and with fibroblasts via N-cadherin-based cell-cell
      contacts. The zonula occludens (ZO) protein-1 is a membrane-associated component
      of both the tight and adherens junctions found at sites of cell-cell contact. In
      most cancers, levels of ZO-1 are typically down-regulated, leading to increased
      motility. Here we report the novel observation that ZO-1 expression is up
      regulated in melanoma cells and is located at adherens junctions between melanoma
      cells and fibroblasts. Immunofluorescence and co-immunoprecipitation studies
      showed co-localization of ZO-1 with N-cadherin. Down-regulation of ZO-1 in
      melanoma cells through RNA interference produced marked changes in cell
      morphology--leading to a less-dendritic, more rounded phenotype. Consistent with
      a role in N-cadherin-based adhesion, RNAi-treated melanoma cells were less
      adherent and invasive when grown in a collagen gel. These data provide the first
      evidence that increased ZO-1 expression in melanoma contributes to the oncogenic
      behavior of this tumor and further illustrate that protein products of genes,
      such as ZO-1, can function in either a pro- or anti-oncogenic manner when
      expressed in different cellular contexts.

PMID- 15855654
TI  - Matrix metalloproteinase-1 associates with intracellular organelles and confers
      resistance to lamin A/C degradation during apoptosis.
AB  - Since the first description of matrix metalloproteinase (MMP)-1 as an
      interstitial collagenase, great importance has been ascribed to this enzyme in
      extracellular matrix remodeling during tumoral, inflammatory, and angiogenic
      processes. As more evidence for the role of MMPs in targeting nonmatrix
      substrates emerges, casual observations that intracellular MMP-1 is found in
      vitro and in vivo prompt investigation of the role that MMP-1 may play on basic
      cell functions such as cell division and apoptosis. Here we show for the first
      time that MMP-1 not only has extracellular functions but that it is strongly
      associated with mitochondria and nuclei and accumulates within the cells during
      the mitotic phase of the cell cycle. On induction of apoptosis, MMP-1 co
      localized with aggregated mitochondria and accumulated around fragmented nuclei.
      Inhibition of this enzyme by RNA interference or treatment with a broad MMP
      inhibitor caused faster degradation of lamin A, activation of caspases, and
      fragmentation of DNA when compared with untreated cells. These observations
      strongly suggest that intracellular association of MMP-1 to mitochondria and
      nuclei confers resistance to apoptosis and may explain the well-known association
      of this enzyme with tumor cell survival and spreading.

PMID- 15855655
TI  - Expression profiling of primary tumors and matched lymphatic and lung metastases
      in a xenogeneic breast cancer model.
AB  - Using a purpose-designed experimental model, we have defined new, statistically
      significant, differences in gene expression between heavily and weakly metastatic
      human breast cancer cell populations, in vivo and in vitro. The differences
      increased under selection pressures designed to increase metastatic proficiency.
      Conversely, the expression signatures of primary tumors generated by more
      aggressive variants, and their matched metastases in the lungs and lymph nodes,
      all tended to converge. However, the few persisting differences among these
      selectively enriched malignant growths in the breast, lungs, and lymph nodes were
      highly statistically significant, implying potential mechanistic involvement of
      the corresponding genes. The evidence that has emerged from the current work
      indicates that selective enhancement of metastatic proficiency by serial
      transplantation co-purifies a subliminal gene expression pattern within the tumor
      cell population. This signature most likely includes genes participating in
      metastasis pathogenesis, and we document manageable numbers of candidates for
      this role. The findings also suggest that metastasis to at least two different
      organs occurs through closely similar genetic mechanisms.

PMID- 15855656
TI  - Effect of acute hyperhomocysteinemia on methylation potential of erythrocytes and
      on DNA methylation of lymphocytes in healthy male volunteers.
AB  - Homocysteine is a precursor of S-adenosylmethionine (AdoMet) and a metabolite of
      S-adenosylhomocysteine (AdoHcy). The ratio of AdoMet to AdoHcy, defined as the
      methylation potential (MP), indicates the flow of methyl groups within the cells.
      Chronic elevations of total homocysteine (tHcy) in plasma correlate with
      increased AdoHcy concentrations, decreased MP, and impaired DNA methylation.
      However, the influence of acute hyperhomocysteinemia on MP is unknown. We induced
      acute hyperhomocysteinemia in 14 healthy volunteers by oral administration of l
      homocysteine (65.1 micromol/kg body wt) in an open, randomized, placebo
      controlled two-period crossover study. The kinetics of tHcy in blood and urine,
      MP in blood, and global DNA methylation in lymphocytes were studied
      systematically during 48 h. Plasma tHcy concentrations reached a peak at 34 +/-
      11 min after an oral load with l-homocysteine and decreased with a half-life of
      257 +/- 41 min (means +/- SD). Only 2.3% of the homocysteine dose were recovered
      in urine. AdoHcy concentrations and MP in whole blood and erythrocytes were not
      affected by the oral homocysteine load. Furthermore, global DNA methylation in
      lymphocytes did not change under these conditions. We found no difference between
      the genotypes of 5,10-methylenetetrahydrofolate reductase in response to the
      homocysteine load. However, AdoMet content in erythrocytes was significantly
      higher in the C677T carriers (CT; n = 7) compared with the CC genotype (n = 7).
      Although chronic elevation of tHcy has been shown to affect MP and DNA
      methylation, acute elevation of plasma tHcy above 20 micromol/l for 8 h is not
      sufficient to change MP and to induce DNA hypomethylation in lymphocytes.

PMID- 15855657
TI  - Activation of the extracellular signal-regulated kinase by complement C5b-9.
AB  - Extracellular signals may be transmitted to nuclear or cytoplasmic effectors via
      the mitogen-activated protein kinases. In the passive Heymann nephritis (PHN)
      model of membranous nephropathy, complement C5b-9 induces glomerular epithelial
      cell (GEC) injury, proteinuria, and activation of phospholipases and protein
      kinases. This study addresses the complement-mediated activation of the
      extracellular signal-regulated kinase (ERK). C5b-9 induced ERK
      threonine202/tyrosine204 phosphorylation (which correlates with activation) in
      GEC in culture and PHN in vivo. Expression of a dominant-inhibitory mutant of Ras
      reduced complement-mediated activation of ERK, but activation was not affected
      significantly by downregulation of protein kinase C. Complement-induced ERK
      activation resulted in phosphorylation of cytosolic phospholipase A2 and was, in
      part, responsible for phosphorylation of mitogen-activated protein kinase
      associated protein kinase-2, but did not induce phosphorylation of the
      transcription factor, Elk-1. Activation of ERK was attenuated by drugs that
      disassemble the actin cytoskeleton (cytochalasin D, latrunculin B), and these
      compounds interfered with the activation of ERK by mitogen-activated protein
      kinase kinase (MEK). Overexpression of a constitutively active RhoA as well as
      inhibition of Rho-associated kinase blocked complement-mediated ERK activation.
      Complement cytotoxicity was enhanced after disassembly of the actin cytoskeleton
      but was unaffected after inhibition of complement-induced ERK activation.
      However, complement cytotoxicity was enhanced in GEC that stably express
      constitutively active MEK. Thus complement-induced ERK activation depends on
      cytoskeletal remodelling and affects the regulation of distinct downstream
      substrates, while chronic, constitutive ERK activation exacerbates complement
      mediated GEC injury.

PMID- 15855658
TI  - A mathematical model of rat distal convoluted tubule. II. Potassium secretion
      along the connecting segment.
AB  - A simulation of the rat distal convoluted tubule (DCT) is completed with a model
      of the late portion, or connecting tubule (CNT). This CNT model is developed by
      relying on a prior cortical collecting duct (CCD) model (Weinstein AM. Am J
      Physiol Renal Physiol 280: F1072-F1092, 2001), and scaling up transport activity
      of the three cell types to a level appropriate for DCT. The major difference
      between the two tubule segments is the lower CNT water permeability. In early CNT
      the luminal solution is hypotonic, with a K(+) concentration less than that of
      plasma, and it is predicted that osmotic equilibration requires the whole length
      of CNT, to end with a nearly isotonic fluid, whose K(+) concentration is
      severalfold greater than plasma. With respect to potassium secretion, early CNT
      conditions are conducive to maximal fluxes, whereas late conditions require the
      capacity to transport against a steep electrochemical gradient. The parameter
      dependence for K(+) secretion under each condition is different: maximal
      secretion depends on luminal membrane K(+) permeability, but the limiting luminal
      K(+) concentration does not. However, maximal secretion and the limiting gradient
      are both enhanced by greater Na(+) reabsorption. While higher CNT water
      permeability depresses K(+) secretion, it favors Na(+) reabsorption. Thus in
      antidiuresis there is a trade-off between enhanced Na(+)-dependent K(+) secretion
      and the attenuation of K(+) secretion by slow flow. When the CNT model is
      configured in series with the early DCT, thiazide diuretics promote renal K(+)
      wasting by shifting Na(+) reabsorption from early DCT to CNT; they promote
      alkalosis by shifting the remaining early DCT Na(+) reabsorption to Na(+)/H(+)
      exchange. This full DCT is suitable for simulating the defects of hyperkalemic
      hypertension, but the model offers no suggestion of a tight junction abnormality
      that might contribute to the phenotype.

PMID- 15855659
TI  - A mathematical model of rat distal convoluted tubule. I. Cotransporter function
      in early DCT.
AB  - A model of rat early distal convoluted tubule (DCT) is developed in conjunction
      with a kinetic representation of the thiazide-sensitive NaCl cotransporter (TSC).
      Realistic constraints on cell membrane electrical conductance require that most
      of the peritubular Cl(-) reabsorption proceeds via a KCl cotransporter,along with
      most of the K(+) recycled from the Na-K-ATPase. The model tubule reproduces the
      saturable Cl(-) reabsorption of DCT but not the micropuncture finding of linear
      Na(+) flux in response to load, more likely a feature of late DCT (CNT). As in
      proximal tubule, early DCT HCO(3)(-) reabsorption is mediated by a luminal
      Na(+)/H(+) exchanger (NHE), but in contrast to proximal tubule, the DCT exchanger
      is operating closer to equilibrium. In the model DCT, two consequences of the
      lesser driving force for NHE exchange are an acidic cytosol and wider swings in
      NHE flux with perturbations of luminal composition. Variations in luminal NaCl
      provide a challenge to cell volume, which can be blunted by volume dependence of
      the KCl cotransporter. Cell swelling can also be induced by increases in
      peritubular K(+) concentration. In this case, volume-dependent inhibition of TSC
      could provide volume homeostasis that also enhances distal Na(+) delivery, and
      ultimately enhances renal K(+) excretion. In the model DCT, proton secretion is
      blunted by peritubular HCO(3)(-), so that there is little contribution by this
      segment to the maintenance of metabolic alkalosis. During alkalosis, the model
      predicts that increasing luminal NaCl concentration enhances NHE flux, so that
      these calculations provide no support for a role of early DCT in recovery from
      Cl(-) depletion alkalosis.

PMID- 15855660
TI  - Ethylene glycol induces hyperoxaluria without metabolic acidosis in rats.
AB  - Ethylene glycol (EG) consumption is commonly employed as an experimental regimen
      to induce hyperoxaluria in animal models of calcium oxalate nephrolithiasis. This
      approach has, however, been criticized because EG overdose induces metabolic
      acidosis in humans. We tested the hypothesis that EG consumption (0.75% in
      drinking water for 4 wk) induces metabolic acidosis by comparing arterial blood
      gases, serum electrolytes, and urinary chemistries in five groups of Sprague
      Dawley rats: normal controls (CON), those made hyperoxaluric (HYP) with EG
      administration, unilaterally nephrectomized controls (UNI), unilaterally
      nephrectomized rats fed EG (HRF), and a metabolic acidosis (MA) reference group
      imbibing sweetened drinking water (5% sucrose) containing 0.28 M NH4Cl. Arterial
      pH, plasma bicarbonate concentrations, anion gap, urinary pH, and the excretion
      of titratable acid, ammonium, phosphate, citrate, and calcium in HYP rats were
      not significantly different from CON rats, indicating that metabolic acidosis did
      not develop in HYP rats with two kidneys. Unilateral nephrectomy alone (UNI
      group) did not significantly affect arterial pH, plasma bicarbonate, anion gap,
      or urinary pH compared with CON rats; however, HRF rats exhibited some signs of a
      nascent acidosis in having an elevated anion gap, higher phosphate excretion,
      lower urinary pH, and an increase in titratable acid. Frank metabolic acidosis
      was observed in the MA rats: decreased arterial pH and plasma HCO3(-)
      concentration with lower urinary pH and citrate excretion with elevated excretion
      of ammonium, phosphate and, hence, titratable acid. We conclude that metabolic
      acidosis does not develop in conventional EG treatments but may ensue with renal
      insufficiency resulting from an oxalate load.

PMID- 15855662
TI  - Improving immunoassay performance by antibody engineering.

PMID- 15855661
TI  - Self-organized density patterns of molecular motors in arrays of cytoskeletal
      filaments.
AB  - The stationary states of systems with many molecular motors are studied
      theoretically for uniaxial and centered (asterlike) arrangements of cytoskeletal
      filaments using Monte Carlo simulations and a two-state model. Mutual exclusion
      of motors from binding sites of the filaments is taken into account. For small
      overall motor concentration, the density profiles are exponential and algebraic
      in uniaxial and centered filament systems, respectively. For uniaxial systems,
      exclusion leads to the coexistence of regions of high and low densities of bound
      motors corresponding to motor traffic jams, which grow upon increasing the
      overall motor concentration. These jams are insensitive to the motor behavior at
      the end of the filament. In centered systems, traffic jams remain small and an
      increase in the motor concentration leads to a flattening of the profile if the
      motors move inwards, and to the buildup of a concentration maximum in the center
      of the aster if motors move outwards. In addition to motor density patterns, we
      also determine the corresponding patterns of the motor current.

PMID- 15855663
TI  - Selection of antibodies and epitopes for cardiac troponin immunoassays: should we
      revise our evidence-based beliefs?

PMID- 15855664
TI  - Serum free light chain measurements move to center stage.

PMID- 15855665
TI  - Newborn screening for lysosomal storage disorders.

PMID- 15855666
TI  - Cystatin C can be measured reliably in capillary blood samples.

PMID- 15855667
TI  - Screening for dysbetalipoproteinemia by plasma cholesterol and apolipoprotein B
      concentrations.

PMID- 15855668
TI  - Effect of two common polymorphisms in the ATP binding cassette transporter A1
      gene on HDL-cholesterol concentration.

PMID- 15855669
TI  - Experimental studies on capturing human leukocytes with cell immuno-chip.

PMID- 15855670
TI  - Hormonal regulation of circulating C-reactive protein in men.

PMID- 15855671
TI  - N-terminal pro-B-type natriuretic peptide concentrations are markedly higher in
      the umbilical cord blood of newborns than in their mothers.

PMID- 15855672
TI  - Preanalytical influences on DPC IMMULITE 2000 intact PTH assays of plasma and
      serum from dialysis patients.

PMID- 15855673
TI  - Anti-actin antibodies in celiac disease: correlation with intestinal mucosa
      damage and comparison of ELISA with the immunofluorescence assay.

PMID- 15855674
TI  - Handling of and direct sampling from primary barcode-labeled pediatric tubes on
      Vitros clinical chemistry analyzers integrated into an enGen work cell.

PMID- 15855675
TI  - Comparison of paraoxonase 1 measurements in serum and in lithium-heparin
      anticoagulated plasma samples.

PMID- 15855676
TI  - Placental mRNA in maternal plasma and its clinical application to the evaluation
      of placental status in a pregnant woman with placenta previa-percreta.

PMID- 15855677
TI  - Clinical relevance of biological variation of B-type natriuretic peptide.

PMID- 15855678
TI  - N-terminal pro-B-type natriuretic peptide concentrations in mothers just before
      delivery, in cord blood, and in newborns.

PMID- 15855679
TI  - Effects of long-term tennis playing on the muscle-bone relationship in the
      dominant and nondominant forearms.
AB  - The relationship between muscle strength and bone mineral density illustrates the
      positive effect of mechanical loading on bone. But local and systemic factors may
      affect both muscle and bone tissues. This study investigated the effects of long
      term tennis playing on the relationship between lean tissue mass and bone mineral
      content in the forearms, taking the body dimensions into account. Fifty-two
      tennis players (age 24.2 +/- 5.8 yrs, 16.2 +/- 6.1 yrs of practice) were
      recruited. Lean tissue mass (LTM), bone area, bone mineral content (BMC), and
      bone mineral density were measured at the forearms from a DXA whole-body scan.
      Grip strength was assessed with a dynamometer. A marked side-to-side difference
      (p < 0.0001) was found in favor of the dominant forearm in all parameters. Bone
      area and BMC correlated with grip strength on both sides (r = 0.81-0.84, p <
      0.0001). The correlations were still significant after adjusting for whole-body
      BMC, body height, or forearm length. This result reinforced the putative role of
      the muscles in the mechanical loading on bones. In addition, forearm BMC adjusted
      to LTM or grip strength was higher on the dominant side, suggesting that tennis
      playing exerts a direct effect on bone.

PMID- 15855680
TI  - Food habits and nutritional status assessment of adolescent soccer players. A
      necessary and accurate approach.
AB  - The aim of this study was to assess the food habits and nutritional status of
      high level adolescent soccer players (N = 33; ages 14-16 yrs) living in their
      home environment. Body composition (height, mass, skinfolds), biochemical and
      hematological parameters, performance in soccer-specific tests (sprinting,
      jumping, intermittent endurance), and dietary intake (weighed food intake method)
      and related behaviors (nutrient supplement use, daily activity profile) were
      assessed. Daily energy expenditure and energy intake were 12.5 MJ and 12.6 MJ,
      respectively. Protein (16% of energy intake; 1.9 g/kg of body mass), lipid (38%),
      and cholesterol (385 mg) intake were above recommendations, while carbohydrates
      (45%) were below. The food intake of these adolescents was based on cereals and
      derivates; meat, fish, and eggs; milk and dairy products; biscuits and
      confectionery; and oil, butter and margarine, which provided 78% of total energy
      intake, 85% of proteins, 64% of carbohydrates, 90% of lipids, and 47% of fiber.
      Although diet provided sufficient iron, 48% of individuals showed iron deficiency
      without anemia. Based on these results, a well designed nutrition intervention
      would be advisable for optimizing performance, and especially for promoting
      healthy eating habits in adolescent soccer players.

PMID- 15855681
TI  - Trunk muscle activity increases with unstable squat movements.
AB  - The objective of this study was to determine differences in electromyographic
      (EMG) activity of the soleus (SOL), vastus lateralis (VL), biceps femoris (BF),
      abdominal stabilizers (AS), upper lumbar erector spinae (ULES), and lumbo-sacral
      erector spinae (LSES) muscles while performing squats of varied stability and
      resistance. Stability was altered by doing the squat movement on a Smith machine,
      a free squat, and while standing on two balance discs. Fourteen male subjects
      performed the movements. Activities of the SOL, AS, ULES, and LSES were highest
      during the unstable squat and lowest with the Smith machine protocol (p < 0.05).
      Increased EMG activity of these muscles may be attributed to their postural and
      stabilization role. Furthermore, EMG activity was higher during concentric
      contractions compared to eccentric contractions. Performing squats on unstable
      surfaces may permit a training adaptation of the trunk muscles responsible for
      supporting the spinal column (i.e., erector spinae) as well as the muscles most
      responsible for maintaining posture (i.e., SOL).

PMID- 15855682
TI  - The isocapnic buffering phase and mechanical efficiency: relationship to cycle
      time trial performance of short and long duration.
AB  - The purpose of this study was to determine the relationship between the isocapnic
      buffer (beta(isocapnic)) and hypocapnic hyperventilation (HHV) phases as well as
      performance in a short (20-min) and long (90-min) time trial (TT) in trained
      athletes. In addition, gross (GE, %) and delta (deltaE, %) efficiency were
      calculated and the relationship between these variables and the average power
      output (W) in each TT was determined. Thirteen male endurance athletes (Mean +/-
      SD age 31 +/- 6 yrs; body mass 75.6 +/- 6.3 kg; height 185 +/- 6 cm) completed a
      continuous incremental test to exhaustion for determination of the
      beta(isocapnic) and HHV phases. A second submaximal test was used to determine GE
      and deltaE. The average power output (W) was measured in a 20-min and 90-min
      cycling TT. The beta(isocapnic) phase (W) was significantly correlated to the
      average power output (W) in the 20-min TT (r = 0.58; p < 0.05), but not in the 90
      min TT (r = 0.28). The HHV phase (W) was not significantly correlated to the
      average power output in the 20-min or 90-min TT. No significant correlation was
      found for GE or for deltaE and performance in the TT. The data from this study
      shows that beta(isocapnic) together with HHV is not likely to be a useful
      indicator of cycle TT performance of 20- to 90-min duration. Furthermore, GE and
      deltaE determined from a submaximal incremental stepwise test are not related to
      cycling TT performance of different duration.

PMID- 15855683
TI  - Does intermittent hypoxia increase erythropoiesis in professional cyclists during
      a 3-week race?
AB  - In this study we examined the effects of intermittent hypoxia exposure (IHE) in a
      group of professional cyclists (n = 6; age 26 +/- 1 yr) competing in the 2001
      Vuelta a Espana. After each daily stage, treated subjects received four 5-min
      bouts of normobaric IHE (mean O2 concentration of 12.6%, simulating a mean
      altitude of 4,000 m) interspersed with 5-min bouts of breathing hotel room air
      (normoxia) until completing a total IHE of 20-min duration. The primary outcome,
      compared to a control group of similar characteristics not receiving IHE (n = 5;
      age 25 +/- 1 yr), was the % increase in erythropoietin (Epo) from the beginning
      to the end of the Vuelta. Statistical analysis showed that Epo increase tended to
      be higher (p = 0.052) in the IHE group than in controls (37.4 +/- 5.8% vs. -4.4
      +/- 19.5%, respectively). However IHE had no effect on reticulocytes or
      erythrocyte count (p > 0.05).

PMID- 15855684
TI  - Association between the ACE I/D gene polymorphism and physical performance in a
      homogeneous non-elite cohort.
AB  - BACKGROUND: I/D polymorphism of the ACE gene may be associated with better
      endurance performance and a stronger response to exercise training. The aim of
      this study was to investigate the association between ACE gene polymorphism and
      athletic performance in a homogeneous cohort. METHODS: Eighty-eight male non
      elite Caucasian Turkish athletes with similar training backgrounds for at least
      for 6 months were studied for ACE gene polymorphisms by PCR analysis. Performance
      on the 60-meter sprint and middle-distance running tests were evaluated. RESULTS:
      The distributions of the ACE I/D genotypes were 20.5%, 40.9%, and 38.6% for II,
      ID, and DD polymorphisms in the whole group (N = 88), respectively. The ACE DD
      genotype frequency was significantly higher in the superior group (56.7%) than in
      the poor (37.9%) and mediocre (20.7%) group in middle-distance running
      performance (chi2 = 11.778; p = 0.019). CONCLUSION: The ACE DD genotype may be
      related to better short-duration aerobic endurance performance. Larger
      homogeneous cohorts may help clarify the association between ACE I/D polymorphism
      and physical performance.

PMID- 15855685
TI  - Effects of heat removal through the hand on metabolism and performance during
      cycling exercise in the heat.
AB  - OBJECTIVE: This two-part study tested the hypotheses that the use of a new
      cooling device, purported to extract heat from the body core through the palm of
      the hand, would (a) attenuate core temperature rise during submaximal exercise in
      the heat, thereby suppressing exercise-associated metabolic changes, and (b)
      facilitate a higher sustained workload, thus shortening the completion time of a
      time-trial performance test. METHODS: In Study 1, 8 male triathletes (age 27.9 +/
      2.0 yrs, mass 77.2 +/- 3.1 kg, VO2peak 59.0 +/- 4.1 ml x min(-1) x kg(-1))
      cycled for 1 hr at the same absolute workload (approximately 60% VO2peak) in a
      heated room (31.9 +/- 0.1 degrees C, 24 +/- 1% humidity) on two occasions
      counterbalanced for cooling (C) or noncooling (NC). In Study 2, 8 similar
      subjects (age 26.9 +/- 2.0 yrs, mass 75.2 +/- 3.7 kg, VO2peak 54.1 +/- 3.1 ml x
      min(-1) x kg(-1)) performed two 30-km cycling time-trial performance tests under
      the same conditions (C(T), NC(T)). RESULTS: In Study 1, cooling attenuated the
      rise in tympanic temperature (T(TY)) (1.2 +/- 0.2 vs. 1.8 +/- 0.2 degrees C; p <
      0.01) and lowered mean oxygen consumption (VO2, 2.4 +/- 0.1 vs. 2.7 +/- 0.1 L x
      min(-1); p < 0.05) and blood lactate (1.7 +/- 0.2 vs. 2.2 +/- 0.2 mmol x L(-1); p
      < 0.01) during exercise. There were no significant differences in respiratory
      exchange ratio (RER), blood glucose, heart rate (HR), face temperature (T(F)), or
      back temperature (T(B)) between NC and C. In Study 2, time to complete 30 km was
      6 +/- 1% less with cooling than without cooling (60.9 +/- 2.0 vs. 64.9 +/- 2.6
      min; p < 0.01). During the last 20% of C(T), subjects sustained a workload that
      was 14 +/- 5% (p = 0.06) higher than NC(T) at the same T(TY) and HR. CONCLUSIONS:
      Heat extraction through the hand during cycle ergometer exercise in the heat can
      (a) lower T(TY), lactate concentration, and VO2 during a submaximal set-workload
      test and (b) reduce the time it takes to complete a 30-km time-trial test.

PMID- 15855686
TI  - Resting membrane potential of rat plantaris muscle fibers after prolonged
      indirect stimulation in situ: effect of glucose infusion.
AB  - The purpose of this study was to determine whether glucose infusion during
      prolonged indirect muscle stimulation (50 Hz for 200 ms every 2.7 s at 5 V) would
      have an effect on resting membrane potential (RMP). The RMP measured at Min 1 in
      the recovery period following stimulation of the rat plantaris muscle for 60 min
      in situ was significantly decreased in control rats, but was back to baseline
      values within 2 min. When glucose was infused ([glucose] approximately 10 mM), no
      change was observed in RMP, and muscle fatigue and the reduction in M-wave peak
      to-peak amplitude were both attenuated. However, muscle force and the electrical
      properties of the membrane were deteriorated both in rats infused with glucose
      and in control rats at Min 2 during the recovery period, at a time when RMP was
      not modified. These observations suggest that the effect of increased circulating
      glucose on fatigue-associated reductions in muscle fiber RMP seems to be modest
      and short-lived. Therefore, the attenuating effect of elevated glucose on muscle
      fatigue responses could be through mechanisms other than those associated with
      maintenance of RMP during fatigue.

PMID- 15855687
TI  - The postexercise increase in the threshold for cutaneous vasodilation and
      sweating is not observed with extended recovery.
AB  - The following study was conducted to evaluate the hypothesis that an increase in
      the postexercise onset threshold for cutaneous vasodilation (Th(VD)) and sweating
      (Th(SW)) would not be observed upon the restoration of baseline mean arterial
      pressure (MAP). Subjects remained either seated resting for 15 min or performed
      15 min of treadmill running at 70% VO2peak followed by either 20- (short) or 60
      min (extended) recovery. At the end of each recovery protocol (20 and 60 min) a
      water perfusion suit was then used to increase mean skin temperature until Th(VD)
      and Th(SW) was noted. Exercise resulted in an increase in Th(VD) and Th(SW) of
      0.24 +/- 0.03 and 0.24 +/- 0.02 degrees C, respectively, above no-exercise for
      the short recovery (p < 0.05). No increase was measured for the extended
      recovery. Postexercise MAP was significantly reduced prior to whole-body warming
      for the short recovery whereas no reduction was measured for the extended
      recovery. The increase in Th(VD) and Th(SW), measured during the early stages of
      recovery, is reversed with the reestablishment of baseline MAP.

PMID- 15855688
TI  - [Resection with pyloric retention as a method for prophylaxis of dumping
      syndrome].
AB  - The aim of the study was the evaluation of efficacy of the resection with pyloric
      retention proposed by the authors as a method for prevention of post
      gastroresectional damping syndrome in patients with ulcers. Resection with
      pyloric retention is performed in six modifications of three basic methods of
      resections. We have the experience of using this approach in 712 clinical cases.
      Among them 237 were women and 475 were men 19-75 years of age. It was shown that
      resection with pyloric retention provides rhythmic evacuation and prevents
      development of damping syndrome and duodenal reflux. It was found that the main
      reasons of the development of postgastroresectional syndromes include wide-area
      mobilization of the stomach and resection of the small curvature, which induce
      insufficiency of cardia, atony, chronic disturbances of the duodenal passing. Due
      to the retention of pyloric function damping syndrome have been developed only in
      3 patients. In all these cases the syndrome was mild. It may be concluded that
      gastric resection with pyloric retention represents the most "physiological"
      intervention and has many advantages in comparison with other methods.

PMID- 15855689
TI  - [Application of transpulmonary thermodilution for cardiac pathologies in
      anesthesiology practice].
AB  - Transpulmonary thermodilution volumetry is invasive method of central hemodynamic
      monitoring which allows us to determine volumetric characteristics of heart,
      volume of blood in thoracic cavity and amount of liquid in intersticium of lungs.
      The method is based on principle of dilution of thermal indicator. Transpulmonary
      thermodilution is complete alternative to blood circulation routine monitoring
      (Swan-Ganz) in a number of cases. It enables anesthesiologist to react as quickly
      as possible to changes of thermodynamic parameters and to minimize probability of
      mistake. All above-mentioned will considerably reduce intra and post operation
      mortality during large-scale operation on body organs of abdominal cavity. Our
      experience of using transpulmonary thermodynamics includes inspection of 97
      patients. The given method is less invasive in comparison with former similar
      methods.

PMID- 15855690
TI  - [Clinico-morphological value of modified nephropexy method].
AB  - We have observed 28 patients operated by modified method of nephropexy. Principle
      of this method is the fixation of kidney on 11 or 12 rib with silk floss #5 or
      #6. Floss is passed subcapsularly around lower pole of the kidney and separately
      on anterior and posterior surfaces. Duration of the operational intervention was
      40-50 min. On the second day after the operation patients were permitted to walk.
      On the long-term follow-up on 5 months to 6 years, we have studied 24 patients.
      All of them felt themselves healthy. Second look excretory urography showed no
      recurrence of nephroptosis. Animal experiment was performed in 5 rabbits and 5
      rats. The same operation was carried out on these animals. After 2-6 months
      kidney and surrounding tissue near used silk floss was studied. Fibrous capsule
      at the places of floss passing was thickened. Parenchyma of kidney was without
      changes. There was weak inflammatory reaction in the tissue around the kidney
      near the floss, which was disappeared at the end of the observation. We propose
      to introduce this modified method of nephropexy in routine practice of urological
      surgery.

PMID- 15855691
TI  - [Alfa-blockade with doxazosin vs tamsulozin in combination of intermittent
      androgen blockade in patients with prostate cancer].
AB  - We have studied the efficacy of Alfa-blockade with Doxazosin vs Tamsulozin in
      combination with Intermittent Androgen Blockade (IAB) in patients with low grade
      prostate cancer. Our clinical trial included: I group (n=15) of patients who
      received doxazosin with IAB and flutamide; II group (n=13) of patients who
      received tamsulozin in combination with IAB and flutamide and III (n=33) group
      with flutamid monotherapy alone. Our results have shown that the combination of
      doxasozin and IAB with the flutamide leads to the better improvement of
      uroflowmetry and IPSS parameters, whereas the tamsulozin and IAB with flutamide
      combination induce those improvements for the longer period during the disease
      remission.

PMID- 15855692
TI  - [Development of the postoperative adhesions in the small pelvic cavity].
AB  - The aim of the study was to determine the frequency and localization of the
      development of postoperative adhesions for different types of surgical
      interventions. For this purpose, 94 patients aged 16 to 47, admitted to the
      department of surgery of I. Zhordania Institute of Human Reproduction in 1998
      2003, who underwent diagnostic and/or operative laparoscopy and had past history
      of laparotomic operations (one or several) have been studied. The study revealed
      that development of postoperative adhesions development in the small pelvic
      cavity takes place in 92,55%. The III- IV degree adhesions are the most
      frequently developed conditions (85,72%) as a result of both gynecological and
      non-gynecological surgeries. Postoperative adhesions developed as result of the
      gynecological surgeries ranked the second (69,23%).

PMID- 15855693
TI  - [Study of immunological status in women with post-term pregnancy].
AB  - The aim of the work was to study immunological homeostasis by comparing the
      immune responses during physiological, post-term and prolonged pregnancy. 51
      women were divided into 3 groups. In the first group there were 13 pregnant women
      with post-term pregnancy, in the second group--8 pregnant women with prolonged
      pregnancy and in the third group--30 pregnant women with term pregnancy. All of
      them were practically healthy pregnant women. We could not find reliable
      differences between full-term and prolonged pregnancies, but in latter cases
      there was a trend towards deficiency of immunologic factors. Post-term pregnancy
      was characterized as an immunophatologic condition. It may be concluded that post
      term newborns must be included into the high-risk group and be permanently
      observed by pediatricians.

PMID- 15855694
TI  - [Oxidative processes in the cervical and vaginal epithelial tissue in patients
      with HPV infection].
AB  - Genital human papilloma virus (HPV) infection is the sexually transmitted
      disease. HPV induces the proliferation of epithelial cells. In the areas of viral
      inclusions vulvovaginal warts, papillomas and condylomas are developing. Some
      serotypes of HPV are known as a significant risk factor of cervical cancer. The
      aim of our study was to detect the conditions of oxidation processes in vaginal
      and cervical tissues in patients with HPV infection. According to our results, in
      patients with HPV, intensification of production of reactive forms of nitrogen
      and oxygen in vaginal and cervical tissues takes place which is the result of
      activation of leukocytes, other phagocyte cells and chaotic flow of blood in
      damaged tissue, as well as interchanging periods of hypoxia and reperfusion.

PMID- 15855695
TI  - [Adrenal hyperandrogenia and lipid metabolism].
AB  - The aim of our study was to evaluate the influence of adrenal androgen-DHEAS on
      lipid metabolism. Observational cross-sectional study was carried out in 57 women
      aged up to 30 years. Clinical, ultrasound, hormonal investigations were
      performed. Markers of lipid metabolism-total cholesterol (TC), triglycerides
      (TG), high density lipoproteides (HDL), low density lipoproteides (LDL), very low
      density lipoproteides (VLDL) and atherogenic index (IAT) were detected. According
      to our results DHEAS decreases the production of TC, TG, LDL, VLDL and blocks
      atherogenic effect of the testosterone. It may be concluded that adrenal androgen
      DHEAS has antiatherogenic effect. It has a long-lasting action on the lipid
      exchange and induces decrease of the level of atherogenic lipids.

PMID- 15855696
TI  - Prognostic significance of apoptosis-related CD95 antigen expression in patients
      with non-Hodgkin's lymphoma.
AB  - Apoptosis-related proteins might play an important role in the pathogenesis and
      sensibility to the chemotherapeutical drugs in patients with non-Hodgkin's
      lymphoma (NHL). In our study we tried to find out the relation between the
      expression of CD95/Fas/Apo-1 antigen and clinical outcome of NHL patients. We
      have measured 24-hour spontaneous apoptosis of peripheral lymphocytes on flow
      cytometer using specific monoclonal anti-CD95 mouse antibodies in 54 patients
      aged 19-76 years. Fas expression proved to be a significant prognostic factor in
      predicting overall survival (OS) because in CD95- (<25%) patients OS was 7% vs.
      CD95+ with 30%. After grouping of patients by IPI score there was no significant
      difference between Fas negative and positive cases (IPI 1 - 50% vs. 68%; IPI 2 -
      50% both), although in unfavorable risk-groups the OS values differed according
      to the CD95 expression (IPI 3 - 20% vs. 70%; IPI 4 - 11% vs. 50%). So we
      conclude, that Apo-1 positive expression appears to be predictive of good overall
      survival as an independent prognostic parameter, as in association with IPI
      criteria.

PMID- 15855697
TI  - [Immunomorphological characteristics of vesicular stomatitis].
AB  - The aim of the present study was to evaluate the immunomorphological
      characteristics of vesicular stomatitis. The patients were divided into 3 groups:
      15 patients with mild stomatitis, 14 patients with moderate stomatitis, 11
      patients with severe stomatitis. The cytological smears were stained by
      Papanicolaou method. We have evaluated indexes of maturation (MI), keratinisation
      (KI), destruction (DI) and inflammation-destruction (IDI). The
      immunocytochemistry was used to evaluate the local immune responses. Anti-CD20
      (pan-B marker), Anti-CD3 (pan-T marker), CD4 (marker of T helper), CD8 (marker of
      T cytotoxic lymphocytes) monoclonal antibodies were used (LSAB, DAB). The
      comparative analysis of cytological indexes in acute and remission phases of
      chronic recurrent ulcerative stomatitis showed that DI and IDI decreased in
      remission phase compared with acute phase, but did not return to norm. It seems
      that inflammation persists in remission phase despite the absence of symptomatic
      vesicular lesion. Therefore, the evaluation of clinical efficacy of treatment
      requires assessing cytological indexes. In various types of vesicular stomatitis
      the dynamic quantitative changes of immunocompetent cells in acute and remission
      phases show the increased number of CD8+ T lymphocytes indicating a potential
      viral etiology and a persistent immunopathological reaction mediated by T cells.
      The presented data can be taken into account during the treatment planning and
      evaluation of therapeutic efficacy.

PMID- 15855698
TI  - [Genetic burden of psychosomatic diseases and exogenous risk-factors of
      cardiovascular diseases in healthy students with different physiological and
      psychological adaptation abilities].
AB  - Exogenous risk factors of cardiovascular diseases and genetic burden of
      psychosomatic pathologies have been studied in practically healthy students with
      various physiological and psychological adaptation abilities for differential
      analysis of the risk for development of cardiological diseases. The complex of
      genetic burden of psychosomatic pathologies and exogenous risk factors was
      significantly more frequent in practically healthy students with strong profile
      of adaptation mechanisms, increased circadian profile, zero type and weak
      persistence of fixated set.

PMID- 15855699
TI  - [Study of the quality of life in patients with isolated systolic hypertension].
AB  - The aim of our study was to evaluate quality of life (QL) of elderly and old
      people diseased with isolated systolic hypertension (ISH) according to their sex
      and age subgroups. 57 patients were involved in the research (19 men, among them:
      11--elderly and 8--old, average age was 69,4+/-5,1; 38 women, 24--elderly, 14-
      old, average age--67,4+/-5,2). The cognitive indicator was evaluated by the form
      MMS (MINI-MENTAL STATE). QL was evaluated according to the inquirer "Evaluation
      of Quality of Life Among Psychosomatic Patients" worked out by Sidorov, Soloviev
      and Novikov. It was shown that the QL was especially low in old people, in men it
      was higher than in women. Investigations conducted for the evaluation of the QL
      of people diseased with ISH enabled us to conclude that somatic, psychological,
      social conditions of the elderly and old people diseased with ISH are extremely
      low.

PMID- 15855700
TI  - [Fascioliasis case in the patient with hepatitis A].
AB  - There is some portion of patients with clinically manifested acute viral
      hepatitis, which are seronegative to hepatitis A markers. They have to be
      differentiated with other patients with B, C, D hepatitis, mechanical jaundice,
      etc. Such clinical cases make physician to recall the parasitic diseases, such as
      fascioliasis, which affects hepatobiliary system, causes prolongation of
      cholestasis and dystrophic changes in the biliary tract and likely to cause liver
      cirrhosis. In the presented case the initial diagnosis was severe acute Hepatitis
      A (anti-HAV IgM+), though the peripheral blood examination showed moderate
      eosinophilia, ultrasound investigation revealed multiple sites of damage in the
      liver, which made us to consider fascioliasis, the latter was confirmed by the
      serological analysis. Appropriate medical treatment was effective and the state
      of the patient has improved.

PMID- 15855701
TI  - [Perolen cream for therapy of rosacea].
AB  - Acne rosacea belongs to the most common inflammatory dermatoses of the face.
      Current treatments for this disease remain unsatisfactory, that's why searching
      for new methods and remedy are very important. For the topical therapy we have
      used a new cream perolen ("New Pharma", Georgia). The main component of the creme
      is the water extract of gastric mucous membrane of cow, which is the source of
      proteolytic ferments. Another main component is a Perilla oil which contains
      unsaturated fatty acids--linolenic and linol, presented in the highest amounts.
      The cream is characterized by bactericidal, bacteriostatical, anti-inflammatory
      and anti-oxidant effects, it also assists to tissue regeneration, make blood
      vessels more elastic and decreases penetration. We have observed 40 patients with
      papulo-pustular subtype of rosacea (25 females and 15 males). Patients were
      divided into two groups. For oral therapy in both groups we used Tetracycline and
      Trichopol. For topical treatment in the first group of patients was used rosamet
      cream and in the second group--perolen cream. Both of these creams were applied
      once daily during 2 months. Reduction of comedones, inflammations, papules,
      pustules and small nodules occurred after one month. Erythema, oedema,
      desquamation improved significantly during the treatment, but the positive
      effects were more prominent in the second group of patients. In conclusion, the
      study shows that topically used cream perelon represents a new approach in the
      management of acne rosacea.

PMID- 15855702
TI  - [Biochemical markers of bone metabolism and cortical bone mineral density in
      young healthy females].
AB  - The goal of the study was to investigate biochemical markers of bone metabolism
      and cortical BMD in young healthy females. 62 young, practically healthy females,
      15-35 years of age were involved in this study. Osteoporosis risk factors were
      assessed by means of the special questionnaire. SOS (speed of sound) was measured
      in the middle of tibia by ultrasound densitometer Sound Scan Compact (Myriad,
      Israel). The bone mineral density of 62 young females varied depending on the
      risk factors such as low body mass, low calcium intake, smoking and unbalanced
      low calorie diet. Body mass index strongly correlated with the BMD. For effective
      control and prevention of osteoporosis, it is essential to identify risk-groups
      among healthy population for follow-up screening and providing adequate measures.

PMID- 15855703
TI  - [Role of the bone mineral density investigation through measuring of peripheral
      dual-energetic x-ray absorption in prevention of fractures in children with
      osteogenesis imperfecta].
AB  - The Osteogenesis imperfecta is hereditary disturbance of collagen biosynthesis.
      Illness is characterized by frequent fractures that consequently cause functional
      disturbance of locomotor system as well as deformation of long tubular bones. The
      distinguishing feature of this illness is the secondary osteoporosis. The latter
      in its turn worsens clinical course and the outcome of the illness. The purpose
      of the present work was the study of bone mineral density in children with
      osteogenesis imperfecta through application of dual energetic x-ray absorption
      measurements. In total 32 patients 1-15 years of age with osteogenesis imperfecta
      have been investigated. The patients have been divided into three age groups.
      Measurement of distal and proximal sections of radius and elbow (ulna) bones was
      carried out using peripheral dual-energetic x-ray absorption measurements in
      order to determine the bone mineral density. Results of the bone mineral density
      (BMD) measurements have proved that children with osteogenesis imperfecta have
      lower indices in comparison with children of the corresponding age group and has
      been registered as 3,76 times lower for 1-7 years old children; 2,3 times lower
      for 7-12 years old children and 1,89 times lower for children 13-15 years of age.
      Having studied the correlation between downgraded bone mineral density and number
      of fracture cases, it was registered that the lower is BMD of cortical layer, the
      higher is the number of fracture cases. Investigating the bone mineral density in
      children with osteogenesis imperfecta provides opportunity to reveal potential
      high risk patients with predisposition to the development of fractures and to
      provide corresponding treatment and preventive measures in these patients.

PMID- 15855704
TI  - [Alternative to donor organs--the method of cultivation from fragments of tissues
      of "new organs" in an organism of the recipient].
AB  - A method of "new liver" growing inside of the recipients' organism as an
      alternative of the donor organs is presented. Experiments were carried out on the
      90 Wistar rats. Animals were divided into 3 equal groups. All of the animals were
      subjected to 40% hepatectomy. The liver fragments were harvested from resected
      lobe. The animals of the I group received liver fragments transplantation into
      the greater omentum pocket, animals of the II group--into the peritoneal cavity
      and animals of the III group--into the "Kakabadze Biocontainer". All animals were
      under the standard vivarium conditions and were sacrificed in the different time
      points. The maximal follow up period was 6 months. Performed investigations have
      shown that vascularized, denuded segment of small intestine is uncial site for
      the engraftment and future development of transplanted liver fragments.

PMID- 15855705
TI  - [The pharmacokinetic effect of haloperidol on DA receptors].
AB  - There is increasing evidence that the metabolism of haloperidol is of major
      significance in the action of the drug. The metabolism of haloperidol is quite
      simple. It keeps only typical oxidative metabolic pathway. Despite of the
      existing knowledge of such pathways we still do not know the exact fate of the
      administered compound in the serum and urine. The aim of the study was the
      investigation of the influence of haloperidol and its oxidative forms on D(A) and
      its compounds in serum. The 12,0 hour investigation demonstrated a protective
      effect on D(A) activity. The D(A) synthesis rate constant was increased to about
      the same level by GBL as well as by haloperidol. Therefore, the differences
      between the two regions in the reactions to the drugs to a large extent could be
      explained by a high and low synthesis of D(A), under controlled conditions in the
      olfactory tubercle and the corpus striatum.

PMID- 15855706
TI  - [Ultrastructural characteristics of gingival mucous cellular composition in
      experimental gingivitis].
AB  - The aim of the work was to estimate morphological changes in cells of gingival
      mucous membrane in the experimental gingivitis model. Fifty rats with the body
      weight of 120-160 gr. were used in the experiment. Gingivitis was modeled by
      front teeth ligation after a preliminary exfoliation of mucous membrane in the
      dental neck area. The specimens were examined by histological method and electron
      microscopy on the 3rd, 5th, 14th and 28th days of the experiment. It has been
      shown that cellular population of plasmocytes, lymphocytes, fibroblasts and mast
      cells take part in the inflammatory process. In all the areas of microcirculation
      occurs transformation of endotheliocytes like papillas; the process of roughening
      of collagenous fibrils indicates their significant role in the inflammatory
      damage of gingiva.

PMID- 15855708
TI  - We are number 1...

PMID- 15855707
TI  - [Monitoring of the radioecological situation of Adjara seacoast].
AB  - One of the most important problems of the modern science is the study of
      biological, physiological and pathological influence of the radiation background
      on the surrounding environment. The disaster in the Chernobyl Atomic Power
      Station vitalized and sharpened the problem, as far as after the accident the
      Black Sea coast was exposed to the pollution. The Radiation background of Adjara
      seacoast has been studied in Georgia during the period of 1997 to 2002. The level
      of the radiation background in open areas lowered from 95 hgy/h to 93 hgy/h. The
      indicators of indoor radiation background have not been essentially changed--110
      hgy/h. The average annual dose of irradiation of the population insignificantly
      lowered from 0,94 mZv/y to 0,937 mZv/y.

PMID- 15855709
TI  - An evaluation of strength of composite resin restorations using different bonding
      agents--an in-vitro study.
AB  - In the recent years, the scope of conservative dentistry with emphasis on
      esthetics has increased by leaps and bounds in enhancing individual personality.
      Composite resins are important for aesthetic restorations in dentistry,
      specifically in operative dentistry. But without bonding agents the success of
      composite restorations is minimized. Researchers are constantly endeavoring to
      improve the quality of bonding agents. The advent of new bonding systems which
      are capable of bonding both enamel & dentin has opened new avenues in the field
      of restorative dentistry. With the market floating with new bonding agents
      claiming superior bonding properties, this study was undertaken to investigate
      the degree of bond strength produced by three commercially available bonding
      agents (Syntac, Scotchbond 1, & Clearfil SE) with composite resin (Esthet-X)
      taken for the experimental procedure.

PMID- 15855710
TI  - Langerhans' cell histiocytosis - A Case Report.
AB  - Langerhan's histiocytosis was formerly known as histiocytosis X and refers to a
      group of conditions characterized by the uncontrolled stimulation and
      proliferation of a normal antigen-processing cell, the Langerhan's cell.
      Mandibular involvement associated with LCH is uncommon in a young child. Most
      reports describing bone involvements in LCH have mainly referred to male subjects
      over 20 years of age. The purpose of this report is to describe a case of
      multifocal bony LCH with mandibular involvement in a 8 year old girl and to
      discuss the appropriate management of such a case.

PMID- 15855711
TI  - The intriguing shadow.
AB  - In the field of radiodiagnosis shadows often raise doubts. On these depend the
      invasive investigative procedures which lead to the final diagnosis. The
      radiologist's word is often considered as the last word in labeling a lesion. The
      treatment protocol which follows makes a world of a difference to the patient. We
      report interesting cases where the patients were radiographed prior to
      orthodontic treatment and coincidentally we found-un believable hidden treasure!
      This is a modest attempt to emphasize that each shadow in a radiograph should be
      scrutinized. Needless to say, the keen observation and experience of the
      diagnostician is of penultimate importance in deciphering the abnormal from the
      normal.

PMID- 15855712
TI  - Evaluation of relative concentration of bacteria in 1% acid red 52- stainable and
      non-stainable dentin.
AB  - Modern management of caries stresses on non-invasive techniques wherever possible
      with maximum protection of sound tooth structure. Various dyes provide a highly
      contrasting visual clue by staining only infected dentin, thus clearly
      demarcating it from the affected normal dentin. Utilizing this property of
      preferential staining of the "Caries Detector" the current study was carried out
      to evaluate the relative concentration of bacteria in 1% Acid Red 52-stainable
      and non-stainable dentin. Sample of ten carious permanent molars or premolars in
      individual patient's mouth and carious teeth extracted due to periodontal
      diseases were examined for the two parts of the clinical study. Each clinical
      aspect was later subjected to laboratory procedure. Cariously infected dentin
      delineated by the solution, "Caries Detector" (1% Acid Red 52 solution in
      propylene glycol) contained six times more CFU/ml than dentin that did not take
      up dye.

PMID- 15855713
TI  - Idiopathic gingival fibromatosis - a case report.
AB  - A case of 4 a year old girl with the complaint of delayed eruption of teeth is
      presented. She had moderate to severe, diffuse gingival enlargement in the
      maxilla and mandible. No deciduous teeth had erupted even at the age of five
      years except for incisal edges of upper, and lower anterior teeth. The diagnosis
      was made based on clinical examination and after ruling out drug and family
      history. Surgical removal of the hyperplastic tissue was done under general
      anesthesia.

PMID- 15855714
TI  - Reactive fibrous hyperplasia associated with a natal tooth.
AB  - A natal tooth is that which is present in the oral cavity at the time of birth.
      Fibrous hyperplasia is a non-specific reactive lesion of soft tissues of unknown
      etiology usually associated with trauma or local irritation. Natal teeth can
      occur as an isolated dental finding, but many times they are associated wilh
      syndromes and developmental disturbances. This is a rare case, where in a natal
      tooth has led to the formation of a reactive fibrous hyperplasia in a four and
      half month old infant, a relationship not reported previously.

PMID- 15855715
TI  - Linear assessment of anteroposterior jaw relationship.
AB  - Three Linear methods of establishing the sagittal relationship of the maxillary
      and mandibular apical bases were compared using Lateral skull radiographs of
      thirty individuals having Class II div. 1 malocclusion. Statistical evaluation
      was done for wit appraisal, AD' distance, and Wylie analysis. The A-D' distance
      is recommended for use during sagittal apical base relationship.

PMID- 15855716
TI  - Taurodontism in deciduous Molars - A Case Report.
AB  - Taurodontism has a very low incidence in deciduous dentition and very few cases
      are reported in the literature, it stands a challenge when it requires pulp
      therapy. This case report presents a case of Taurodontism in deciduous molars of
      a five year old male child which required pulp therapy. A clinical and
      radiographic follow up of the patient is discussed.

PMID- 15855717
TI  - Crown dilaceration of maxillary right permanent central Incisor - A case report.
AB  - Dilaceration of teeth can occur as a result of trauma to its primary
      predecessors. Root dilaceration is more common than dilaceration of the crown. A
      rare case of crown dilaceration of maxillary permanent central incisor has been
      reported in this article.

PMID- 15855718
TI  - Comparative evaluation of trace elements and residual bacterial contents of
      different brands of bottled waters.
AB  - The present study was conducted to evaluate the comparative levels of cariostatic
      and caries potentiating trace elements and to detect residual coliform bacteria
      in six different bottled waters. Trace elements and fluoride were estimated using
      Inductively Coupled Plasma Optical Emission Spectrometer and fluoride ion
      electrode respectively. Coliform bacteria were detected by multiple tube method.
      It was found that, trace elements were below the significant caries potentiating
      or cariostatic levels and none of the samples showed coliform bacterial growth.
      It can be concluded from the present study that these water samples can be safely
      consumed without any dental ill effects.

PMID- 15855719
TI  - Biochemical and molecular pharmacological aspects of transporters as determinants
      of drug disposition.
AB  - Membrane transporters are integral membrane proteins typically having 12
      transmembrane domains. Most of the SLC family transporters consist of 300-800
      amino acid residues with a molecular mass of 40-90 kDa, while the corresponding
      values of ABC family transporters are 1,200-1,500 residues and 140-180 kDa,
      respectively. Each transporter has a characteristic tissue distribution and
      subcellular localization. I have isolated cDNAs of various transporters,
      including oligopeptide transporter PEPT1, monocarboxylic acid transporter MCT1
      and organic cation/carnitine transporters (OCTNs), and determined their tissue
      distribution and subcellular localization. I have also determined the absolute
      expression levels of transporters to evaluate their relative contributions to
      drug transport in various tissues. It is important to note that expression levels
      of transporters can be changed under various physiological conditions and by
      administration of drugs. Changes in expression level, subcellular localization
      and functional properties can all be involved in inter-individual differences in
      drug pharmacokinetics. Transporters are among the key determinants of drug
      disposition.

PMID- 15855720
TI  - Regional difference in P-glycoprotein function in rat intestine.
AB  - It has been reported that inhibition of the P-glycoprotein (P-gp) results in the
      improved absorption of P-gp substrate in the intestinal tract. In fact, the
      increased permeability of P-gp substrate across the intestinal epithelium was
      observed following inhibition of P-gp in in vitro experiments. To develop the
      formulation containing P-gp inhibitor and P-gp substrate for practical use, it is
      necessary to know whether the results obtained in the in vitro experiments are
      reproducible at whole body level. It is also important to find out the regional
      difference of the P-gp activity in the intestinal tract. In this study, we
      examined whether verapamil, a specific inhibitor of P-gp, improves the absorption
      of rhodamine123 (Rho123), a substrate of P-gp, from the jejunum, ileum, and colon
      of rats using the in situ loop method. The water content in the loop decreased
      during the experiment, resulting in a significant change of the Rho123
      concentration in the loop. Thus, to accurately determine the absorption rate of
      Rho123, it was necessary to measure the water movement. It was found that there
      was a regional difference in the water movement, i.e., greatest in colon,
      followed by ileum. Verapamil did not change the water movement in any intestinal
      regions. When the concentration of Rho123 in the loop was corrected by water
      movement, the Rho123 clearance was in the order of ileum (1.15 microL/min/cm),
      colon (0.83 microL/min/cm) and jejunum (0.47 microL/min/cm). In the presence of
      verapamil, the Rho123 clearance was significantly increased at jejunum and ileum
      but not in colon (ileum: 2.08 microL/min/cm, colon: 1.14 microL/min/cm, jejunum:
      1.28 microL/min/cm). These results suggest that P-gp inhibits the drug absorption
      in jejunum and ileum. From these results, it is possible to evaluate the role of
      P-gp and its regional difference in the in situ experiments. In particular, the
      inhibition of P-gp results in an increase in absorption of the P-gp substrate
      limited to jejunum and ileum.

PMID- 15855721
TI  - Evaluation of phenytoin dosage regimens based on genotyping of CYP2C subfamily in
      routinely treated Japanese patients.
AB  - Two research groups have reported the effect of genetic polymorphisms of CYP2C9
      and CYP2C19 on the pharmacokinetic parameters of phenytoin in Japanese epileptic
      patients. We measured the plasma phenytoin concentrations at steady-state in 20
      routinely treated Japanese patients, and evaluated the usefulness of genotyping
      the CYP2C subfamily in predicting plasma concentrations and determining the
      dosage regimens of phenytoin. The plasma phenytoin concentrations predicted by
      genotypes of the CYP2C subfamily were well correlated with the observed
      concentrations in some patients, but not in some patients. The pharmacokinetic
      parameters (Vmax and Km) in individual patients, which were obtained from
      population estimates according to Bayes' theorem, showed considerable
      interindividual variability even among patients with the same genotype. In
      addition, we assessed the effect of plasma protein binding on the residual
      interindividual variability in the clearance of phenytoin; however, there was no
      significant correlation between the unbound fraction and the intrinsic metabolic
      activity (Vmax/Km). These findings suggested that the mechanism responsible for
      the large variability in the clearance of phenytoin is not completely resolved,
      and that we should not overestimate the usefulness of genotyping the CYP2C
      subfamily in determining the dosage regimens of the drug.

PMID- 15855722
TI  - The frequency of candidate alleles for CYP2D6 genotyping in the Japanese
      population with an additional respect to the -1584C to G substitution.
AB  - The -1584C/G single nucleotide polymorphism (SNP) in the promoter region of
      CYP2D6 was suggested to have the potential to influence CYP2D6 activity. In this
      report, we demonstrated the frequencies of -1584C to G substitution-related
      alleles, such as CYP2D6*2, CYP2D6*21, CYP2D6*35 and CYP2D6*41, in the Japanese
      population. The frequencies of CYP2D6*2, *41 and *21 were 0.102, 0.026 and 0.005,
      respectively. We also showed a relationship between the SNP and other common
      alleles, CYP2D6*4, *5, *10, *14 and *18. Interestingly, the SNP was detected in
      all three subjects carrying CYP2D6*14. This finding suggests the -1584G is
      included in the CYP2D6*14 allele, which is a null-allele characteristic to the
      Japanese population. This report presents practical information on CYP2D6 alleles
      that should be considered in the pharmacokinetic study of CYP2D6 substrates in
      the Japanese population.

PMID- 15855723
TI  - Effect of isoniazid on the pharmacodynamics of cefazolin-induced seizures in
      rats.
AB  - Both isoniazid (INH) and cefazolin (CEZ) can have serious adverse effects on the
      central nervous system (CNS), causing seizures. In this study, we investigated
      the effect of INH on the pharmacodynamics of CEZ-induced seizures in rats. Male
      Wistar rats pretreated with INH (150 mg/kg i.p.) or saline received an
      intravenous infusion of CEZ at 3.2 g/h/rat until the onset of seizures, then
      samples of cerebrospinal fluid (CSF), blood (for serum), and brain were obtained
      immediately. The administration of INH was associated with a reduction in the
      total dose of CEZ required to produce seizures. The concentrations of CEZ in
      serum, brain, and CSF in INH-treated rats at the onset of seizures were
      significantly lower than those in control rats. In rats coadministered with
      pyridoxine (150 mg/kg s.c.), the concentration of CEZ in CSF at the onset of
      seizures was significantly higher than that in rats administered INH only. These
      results suggest that INH potentiates the sensitivity of the CNS to CEZ-induced
      seizures, and that the increased sensitivity is associated with the inhibition of
      vitamin B(6) metabolism by INH.

PMID- 15855724
TI  - Induction of human CYP1A2 and CYP3A4 in primary culture of hepatocytes from
      chimeric mice with humanized liver.
AB  - Chimeric mice with near-completely humanized liver were constructed by
      transplantating hepatocytes from a Japanese and Caucasian donor. In the present
      study, we investigated the induction of human CYP1A2 and CYP3A4 mRNA in a primary
      culture of the cryopreserved chimeric mouse hepatocytes. beta-naphthoflavone
      (beta-NF) and rifampicin (Rif) were used as typical cytochrome P450 (CYP)
      inducers for CYP1A2 and CYP3A4, respectively. Analysis was performed by the real
      time reverse-transcription polymerase chain reaction method. CYP1A2 mRNA in the
      primary culture of chimeric mouse hepatocytes in mice No. 1, 2, and 3 was
      significantly increased 3.8-, 6.3-, and 3.3-fold by 5 microM beta-NF exposure,
      respectively, compared with the 0.1% DMSO treated control (p<0.01). CYP3A4 mRNA
      in the primary culture of chimeric mouse hepatocytes in mice No. 1, 2, and 3 was
      significantly increased 8.4-fold (p<0.001), 2.2-fold (p<0.01), and 2.3-fold
      (p<0.05) by 50 microM Rif exposure, respectively, compared with the 0.1% DMSO
      treated control. The present study demonstrated that a primary culture of
      cryopreserved hepatocytes from chimeric mice with humanized liver could be used
      for evaluating the induction of drug metabolizing enzymes in human. This in vitro
      method may be a useful method for screening the induction potency of new drug
      candidates on drug metabolizing enzymes.

PMID- 15855725
TI  - Role of human liver cytochrome P450 2C9 in the metabolism of a novel
      alpha4beta1/alpha4beta7 dual antagonist, TR-14035.
AB  - The metabolism of a novel dual antagonist for alpha4beta1/alpha4beta7 integrin,
      TR-14035, and the role of polymorphic enzyme responsible for this metabolism were
      investigated. Human liver microsomes catalyzed the NADPH-dependent metabolism of
      TR-14035 to a primary metabolite, O-desmethyl TR-14035. This formation was
      completely blocked by both sulfaphenazole, a selective CYP2C9 inhibitor, and
      CYP2C9 antibody, whereas potent inhibitors selective for other CYPs exhibited
      little effects. Of 12 recombinant CYPs examined, O-desmethyl metabolite was
      principally formed by CYP2C9. CYP1A1, an extrahepatic enzyme, also had this
      activity (about one-fourth of CYP2C9). Utilizing recombinant CYP2C9*1, K(m) and
      V(max)/K(m) values of 23.3 microM and 0.284 microL/min/pmol CYP2C9, respectively,
      were obtained for the O-desmethyl formation, which were quite similar to those in
      CYP2C9*2 enzyme. In contrast, V(max)/K(m) value in recombinant CYP2C9*3 was
      approximately one-sixth of CYP2C9*1 and *2. In agreement, kinetics studies using
      human liver microsomes with CYP2C9*1/*1, *2/*2 and *3/*3 genotypes revealed that
      the V(max)/K(m) value in *2/*2 microsomes was comparable to that in wild type
      microsomes, in contrast, that in *3/*3 microsomes was reduced. These results
      demonstrate CYP2C9 is a primary enzyme mediating the O-desmethylation of TR-14035
      in human liver. In homozygotes of CYP2C9*3, the metabolic clearance of TR-14035
      should be decreased compared with homozygotes of CYP2C9*1 or 2.

PMID- 15855726
TI  - Urinary excretion of phenytoin metabolites, 5-(4'-hydroxyphenyl)-5
      phenylhydantoin and its O-glucuronide in humans and analysis of genetic
      polymorphisms of UDP-glucuronosyltransferases.
AB  - The anticonvulsant agent phenytoin (5,5-diphenylhydantoin) is mainly excreted as
      5-(4'-hydroxyphenyl)-5-phenylhydantoin (4'-HPPH) O-glucuronide in humans.
      Previously, we demonstrated that the glucuronidation of 4'-HPPH is catalyzed by
      multiple UDP-glucuronosyltransferases (UGTs) of UGT1A1, UGT1A4, UGT1A6, and
      UGT1A9. Since 4'-HPPH may be bioactivated to a reactive metabolite by peroxidase,
      the glucuronidation in considered to be a detoxification pathway. In the present
      study, we investigated the relationship between the extent of interindividual
      variability in the urinary excretion levels of 4'-HPPH and its O-glucuronide and
      genotyping of CYP2C9, CYP2C19, UGT1A1, UGT1A6, and UGT1A9. 4'-HPPH and its
      glucuronide in urine samples from 15 patients to whom phenytoin was administered
      were measured by liquid chromatography-tandem mass spectrometry. When the molar
      ratio of 4'-HPPH O-glucuronide/4'-HPPH was calculated as an index of
      glucuronidation, a large interindividual variability (11 fold) was observed in
      the 15 patients. Phenytoin is metabolized to 4'-HPPH by CYP2C9 and CYP2C19 in
      which there are genetic polymorphisms. Although 5 patients were genotyped as
      heterozygotes of mutated alleles of CYP2C9 or CYP2C19 genes, no relationship with
      the interindividual difference in the total excretion levels of 4'-HPPH and its O
      glucuronide was observed. The UGT1A1*6, UGT1A1*28, UGT1A1*60 and UGT1A6*2 alleles
      were found in 1, 3, 6, and 8 patients, respectively. Although there was no
      relationship between the genetic polymorphisms of UGT1As and the interindividual
      difference in the 4'-HPPH glucuronidation, the large interindividual variability
      of 4'- HPPH glucuronidation may contribute to interindividual differences in
      toxic reactions to phenytoin.

PMID- 15855727
TI  - Genetic variations and haplotypes of UGT1A4 in a Japanese population.
AB  - Nineteen genetic variations, including 11 novel ones, were found in exon 1 and
      its flanking region of the UDP-glucuronosyltransferase (UGT) 1A4 gene from 256
      Japanese subjects, consisting of 60 healthy volunteers, 88 cancer patients and
      108 arrhythmic patients. These variations include -217T>G and -36G>A in the 5'
      flanking region, 30G>A (P10P), 127delA (43fsX22; frame-shift from codon 43
      resulting in the termination at the 22nd codon, codon 65), 175delG (59fsX6),
      271C>T (R91C), 325A>G (R109G), and 357T>C (N119N) in exon 1, and IVS1+1G>T,
      IVS1+98A>G and IVS1+101G>T in the following intron. Among them, 127delA and
      175delG can confer early termination of translation, resulting in an immature
      protein that probably lacks enzymatic activity. Variation IVS1+1G>T is located at
      a splice donor site and thus may lead to aberrant splicing. Since we did not find
      any significant differences in the frequencies of all the variations among the
      three subject groups, the data were analyzed as one group. The allele frequencies
      of the novel variations were 0.006 for IVS1+101G>T, 0.004 for 30G>A (P10P) and
      357T>C (N119N), and 0.002 for the 8 other variations. In addition, the two known
      nonsynonymous single nucleotide polymorphisms (SNPs), 31C>T (R11W) and 142T>G
      (L48V), were found at 0.012 and 0.129 frequencies, respectively. The SNP 70C>A
      (P24T), mostly linked with 142T>G (L48V) in German Caucasians, was not detected
      in this study. Sixteen haplotypes were identified or inferred, and some
      haplotypes were confirmed by cloning and sequencing. It was shown that most of
      142T>G (L48V) was linked with -219C>T, -163G>A, 448T>C (L150L), 804G>A (P268P),
      and IVS1+43C>T, comprising haplotype *3a; haplotype *4a harbors 31C>T (R11W);
      127delA (43fsX22) and 142T>G (L48V) were linked (haplotype *5a); 175delG (59fsX6)
      was linked with 325A>G (R109G) (*6a haplotype); and -219C>T, -163G>A, 142T>G
      (L48V), 271C>T (R91C), 448T>C (L150L), 804G>A (P268P), and IVS1+43C>T comprised
      haplotype *7a. Our results provide fundamental and useful information for
      genotyping UGT1A4 in the Japanese and probably Asian populations.

PMID- 15855728
TI  - [Regulation of insulin signaling and its disorder].

PMID- 15855729
TI  - [Oxidative stress in diabetes].

PMID- 15855730
TI  - [Regulation of phosphorylation of tau by insulin and Ca2+ signals].

PMID- 15855731
TI  - [Brain aging and insulin signals].

PMID- 15855732
TI  - [Expression of insulin receptor and its signaling molecules: regulatory
      mechanisms in neuronal cells].

PMID- 15855733
TI  - [Genome-wide analysis of single nucleotide polymorphisms].

PMID- 15855734
TI  - [Use of the DNAchip in post-genomic pharmacological science].

PMID- 15855735
TI  - [Bioinformatics].

PMID- 15855736
TI  - Regulation of cyclic nucleotides in the urinary tract.
AB  - Cyclic nucleotide levels are controlled through their synthesis from nucleotide
      triphosphates by cyclases and their degradation to 5'-monophosphates by
      phosphodiesterases (PDEs). Components controlling cyclic AMP-induced relaxation
      in the urinary tract include receptors, inhibitory and stimulatory G-proteins,
      isoforms of adenylyl cyclase and PDEs. The responsiveness of PDEs to a variety of
      physiological challenges is related to the presence of multiple families of
      isoenzymes with specific localization within tissues and within cells. At least
      11 families of PDEs encode more than 50 PDE proteins produced in mammalian cells.
      In the urinary tract, characterization of PDE isoforms has lagged behind other
      systems and much of the literature was published prior to identification of PDE7,
      8, 9, 10, 11. Specific PDE inhibitors regulate smooth muscle function in the
      bladder, urethra, prostate and ureter. The pharmacological potential of these
      inhibitors may include treatment of urge incontinence and the low compliance
      bladder, and treatment of prostate cancer. G-proteins also regulate cyclic AMP
      production. Changes in specific G- protein isoforms with aging, most prominently
      Gialpha2, cause decreased relaxation response in the aging bladder. As we have
      seen here with aging and certainly in other disease processes, levels of the
      components of adenylyl cyclase/phosphodiesterase/protein kinase can change and
      thus affect the relaxation response. By exploitation of differences in PDE
      expression in disease, such as the overexpression of PDEs in cancer, treatment
      options may present themselves.

PMID- 15855737
TI  - Effects of dual-action genistein derivatives on relaxation in rat aorta.
AB  - Protein tyrosine kinases and nitric oxide (NO) play important roles in several
      cardiovascular diseases. In this study, we examined the actions of two compounds,
      each has structure of genistein (a tyrosine kinase inhibitor) and an NO donor, on
      endothelium-independent relaxation responses in the isolated rat aorta. By
      rational drug design, genistein was modified to acquire an NO donor, and we
      synthesized two such compounds (G-II, G-VI). These compounds and genistein
      induced dose-dependent relaxation responses in endothelium-denuded aortic strips,
      the rank order of potencies being G-VI > G-II > genistein. Incubation of
      endothelium-denuded strips with 1H-[1,2,4] oxadiazolo[4,3-a]-quinoxalin-1-one
      (ODQ, 10 microM), a guanylyl cyclase inhibitor, inhibited both the G-II- and G-VI
      induced relaxations, but not the genistein-induced relaxation. The residual
      relaxations induced by these two compounds were similar to the genistein-induced
      relaxation. Incubation of endothelium-denuded strips with lysophosphatidylcholine
      (LPC, 20 microM)-which is a major atherogenic lysophospholipid component of
      oxidized low-density lipoprotein and is known to activate tyrosine kinase-caused
      a significant rightward shift in the dose-response curve for genistein. LPC also
      shifted the G-II- and G-VI-induced relaxation curves to the right; however, these
      relaxations in the presence of LPC were greater than that induced by genistein.
      The sodium nitroprusside-induced relaxation in endothelium-denuded strips was
      similar between in the absence and presence of LPC. These results suggest that
      each of our newly developed G-II and G-VI compounds has a dual action, as an NO
      donor and a tyrosine kinase inhibitor. These compounds may be useful against
      certain cardiovascular diseases.

PMID- 15855738
TI  - Diabetes-related changes in contractile responses of stomach fundus to endothelin
      1 in streptozotocin-induced diabetic rats.
AB  - The contractile response of the stomach fundus to endothelin-1 (ET-1) was
      examined in streptozotocin (STZ)-induced diabetic rats. In STZ-diabetic rats
      (versus age-matched control rats) (a) ET-1 caused a longer-lasting contraction of
      stomach fundus strips, and (b) in the dose-response curve, the ET-1-induced
      contraction was significantly greater for a given concentration (3 x 10(-7) to
      10(-7) M). Although repeated application of ET-1 led to desensitization, the
      desensitization was less pronounced in STZ-diabetic rats than in the controls.
      The density of the binding sites for [(125)I]-ET-1 was increased in the diabetic
      stomach fundus (versus the controls), but Kd values were similar between the two
      groups. The ET(B) receptor mRNA expression level was significantly increased in
      the diabetic stomach fundus. These results suggest that the diabetes-related
      enhancement of the ET-1-induced contraction of the stomach fundus may be due to
      an increase in the ET(B) receptor population.

PMID- 15855739
TI  - Examination of the role of cholinergic myenteric neurons with the impairment of
      neural reflexes in the ileum of c-kit mutant mice.
AB  - Our previous study showed that impairment of ascending and descending neural
      reflexes in the ileum of the c-kit mutant, W/W(V), mice is due to a loss of
      interstitial cells of Cajal present at the myenteric plexus region (ICC-MY) in
      the mutant. In the present study, cholinergic interneurons were thought to be
      involved in these pathways, since hexamethonium, an antagonist of the nicotinic
      ACh receptor, significantly inhibited both neural reflexes in wild type mice.
      Therefore, we examined whether the loss of ICC-MY affects cholinergic
      interneurons involved in these pathways. Immunohistochemistry with anti-choline
      acetyltransferase revealed that there was no difference in the numbers of
      immunopositive cells in the myenteric plexus region between the wild type and
      mutant mice. In addition, there was no difference in the extent of spontaneous
      and EFS-evoked ACh release from longitudinal muscle with myenteric plexus
      preparations between the wild type and mutant mice. Exogenously added nicotine
      induced contraction or relaxation of ileal circular muscle in the absence or
      presence of atropine, respectively, to a similar extent in both the wild type and
      mutant mice. These results suggest that loss of ICC-MY resulted in an impairment
      of the ascending and descending reflex pathways at the step before activation of
      cholinergic interneurons.

PMID- 15855740
TI  - Changes of lymphocyte populations in pediatric steroid-sensitive nephrotic
      syndrome are more pronounced in remission than in relapse.
AB  - BACKGROUND/AIM: Although clinical and immunological findings in steroid-sensitive
      nephrotic syndrome (SSNS) favor an immunopathogenesis, many issues remain
      unsolved. Comprehensive studies analyzing cellular and humoral immunity in SSNS
      are scarce, and few studies addressed the effect of steroids on immunological
      factors. METHODS: We therefore performed a cross-sectional study of T and B
      lymphocyte populations in 89 children during the different stages of the disease
      and related the findings to parameters of humoral immunity and treatment with
      steroids. RESULTS: In untreated relapse, an increase in the proportion of
      activated CD3+ lymphocytes with a concomitant reduction of CD19+ B cells was
      noted compared to healthy controls. Conversely, patients with steroid dependency,
      relapsing on alternate-day steroids, showed a decline of the absolute numbers as
      well as proportion of CD4+ lymphocytes but a relative increase in CD19+ B cells,
      compared to healthy controls. Also untreated remission was characterized by an
      absolute and relative decrease in CD4+ lymphocytes compared to healthy controls
      which was accompanied by a significant increase in the proportion of CD8+ and
      also activated CD3+ lymphocytes. Steroid-induced remission resulted in
      suppression of absolute and relative CD4+, while absolute and relative B cells
      were upregulated in this group compared to untreated remission. SUMMARY AND
      CONCLUSION: Alterations of lymphocyte populations in SSNS are not limited to
      relapse but seem to be more pronounced in remission and show a different profile
      with steroid treatment. Changes of lymphocyte populations do not only affect T
      but also B lymphocytes, which may be of relevance in the pathogenesis of this
      disorder.

PMID- 15855741
TI  - Differential effects of antihypertensive drugs on renal and glomerular
      hemodynamics and injury in the chronic nitric-oxide-suppressed rat.
AB  - BACKGROUND/AIMS: Prolonged nitric oxide synthase (NOS) inhibition with N(omega)
      nitro-L-arginine methylester in normotensive and hypertensive rats has been
      demonstrated to produce severe systemic and glomerular hypertension with
      glomerular sclerosis, and these changes have become a useful experimental model
      of hypertensive nephrosclerosis. This review summarizes data from our serial
      studies as well as work of others who are also investigating the effects of the
      commonly used antihypertensive drugs (including calcium antagonist, angiotensin
      converting enzyme inhibitor, angiotensin II type 1 receptor blocker, aldosterone
      antagonist and thiazide diuretic) on renal and glomerular hemodynamics, renal
      function and glomerular histopathology using this model. METHODS: A Medline
      search was performed to identify the relevant literature describing renal effects
      of antihypertensive drugs in models of hypertension and nephrosclerosis produced
      or exacerbated by NOS inhibition. RESULTS: Existing data have indicated that most
      of these drug classes have produced dramatic renoprotective effects, structurally
      or functionally, on nephrosclerosis induced by prolonged NOS inhibition.
      CONCLUSION: This review of experimental studies has provided strong evidence
      supporting the clinical benefits of antihypertensive drugs for hypertensive
      patients with renal impairment particularly those with endothelial dysfunction
      associated with NOS deficiency.

PMID- 15855742
TI  - The primary hyperoxalurias: an algorithm for diagnosis.
AB  - BACKGROUND/AIMS: The primary hyperoxalurias (PHs) are inborn errors of metabolism
      resulting in increased urinary excretion of oxalate. Nephrolithiasis,
      nephrocalcinosis, and renal failure result. Renal failure can occur as early as
      infancy or as late as the sixth decade of life, and if not addressed promptly,
      results in severe morbidity and mortality related to systemic oxalate deposition
      (oxalosis). Clinicians are likely to encounter few PH patients during a
      practicing lifetime. Definitive diagnosis requires special studies performed in
      only a small number of laboratories worldwide. Accordingly, delays in diagnosis
      are common. METHODS: An evidence-based guideline for diagnosis was developed.
      RESULTS: Patients with stones or nephrocalcinosis in childhood, recurrent calcium
      oxalate stones in adulthood, or renal insufficiency associated with stones or
      nephrocalcinosis should be evaluated for PH. A systematic approach to measurement
      of urine oxalate, glycolate and glycerate, and plasma oxalate is provided. Age
      related variation in urine oxalate requires attention to normal ranges. Molecular
      analysis for mutations of the AGXT gene (PH, type I) or GRHPR gene (PH, type II)
      is definitive in some patients, while liver enzyme analysis is required for
      confirmation of the diagnosis in the remainder. CONCLUSION: An evidence-based
      algorithm will facilitate recognition and diagnosis of patients with the PHs,
      permitting earlier treatment.

PMID- 15855743
TI  - Evolution of bower complexity and cerebellum size in bowerbirds.
AB  - To entice females to mate, male bowerbirds build elaborate displays (bowers).
      Among species, bowers range in complexity from simple arenas decorated with
      leaves to complex twig or grass structures decorated with myriad colored objects.
      To investigate the neural underpinnings of bower building, we examined the
      contribution of variation in volume estimates of whole brain (WB), telencephalon
      minus hippocampus (TH), hippocampus (Hp) and cerebellum (Cb) to explain
      differences in complexity of bowers among 5 species. Using independent contrasts,
      we found a significant relationship between bower complexity and Cb size. We did
      not find support for correlated evolution between bower complexity and WB, TH, or
      Hp volume. These results suggest that skills supported by the cerebellum (e.g.,
      procedural learning, motor planning) contribute to explaining the variation in
      bower complexity across species. Given that male mating success is in part
      determined by female choice for bower design, our data are consistent with the
      hypothesis that sexual selection has driven enlargement of the cerebellum in
      bowerbirds.

PMID- 15855744
TI  - Can screening for retinopathy of prematurity be reduced?
AB  - BACKGROUND: As screening for retinopathy of prematurity (ROP) is costly, time
      consuming for the ophthalmologist and discomforting for the neonate, the minimum
      number of infants should be screened for ROP, without missing infants with severe
      ROP, at risk for threshold ROP. OBJECTIVES: To develop a diagnostic screening
      guideline for ROP that would safely reduce the number of ROP screening
      funduscopies in our department. METHODS: Data of 275 infants admitted between
      1996 and 2000 and screened for ROP according to our Dutch National guideline were
      studied. Significant risk factors for ROP were calculated, using logistic
      regression analysis and used to develop a guideline. The discriminative power of
      the guideline was evaluated using the area under the curve for the receiver
      operating characteristic curve. RESULTS: Significant risk factors for ROP were:
      gestational age, birth weight and number of erythrocyte transfusions within the
      first 4 weeks of life. The combination of these 3 factors resulted in the highest
      area under the curve: 0.793. Using these 3 factors, a diagnostic screening
      guideline for ROP was developed: if birth weight + 2 x (gestational age - 20) - 6
      x erythrocyte transfusion value within the first 4 weeks of life >or=34, no
      screening for ROP is necessary. Using this guideline, 22.2% of the infants of the
      study group could have been excluded from screening; 3.8% of the infants with ROP
      stages 1-2 would have been missed. CONCLUSION: In our department, ROP screening
      can be safely reduced using our diagnostic screening guideline.

PMID- 15855745
TI  - Can ROP blindness be eliminated?

PMID- 15855746
TI  - The pathogenesis of gastrointestinal bacterial overgrowth.
AB  - The normal indigenous intestinal microflora consists of about 10(15) bacteria
      that under physiological conditions reside mainly in the lower gastrointestinal
      tract. Bacterial overgrowth implies abnormal bacterial colonization of the upper
      gut, resulting from failure of specific defense mechanisms restricting
      colonization under physiological conditions. At present two types of bacterial
      overgrowth with defined pathogenesis can be distinguished: (1) gastric overgrowth
      with upper respiratory tract microflora resulting from selective failure of the
      gastric acid barrier, and (2) gastrointestinal overgrowth with Gram-negative
      bacilli (enteric bacteria) resulting from failure of intestinal clearance.
      Helicobacter pylori-induced gastritis of the oxyntic mucosa is the main cause of
      acquired failure of the gastric acid barrier, which is common among the healthy
      elderly. Intestinal clearance may fail as the result of impaired intestinal
      peristalsis or anatomical abnormalities that alter luminal flow. Impaired
      peristalsis is associated with conditions interfering with intestinal
      neuromuscular function including myopathic, neuropathic, autoimmune, infectious,
      inflammatory, metabolic, endocrine, and neoplastic diseases. Anatomical
      abnormalities are mainly the result of gastrointestinal surgery, intestinal
      diverticula or fistula. Combined failure of intestinal clearance and the gastric
      acid barrier results in more severe colonization with Gram-negative bacilli. Gram
      negative bacilli are uncommon in the upper gut of otherwise healthy individuals
      with gastric hypochlorhydria, being acquired (H. pylori) or drug-induced.
      Significant bacterial overgrowth with Gram-negative bacilli is a rational in the
      search for an explanation to optimize clinical management. The clinical
      significance of colonization with upper respiratory tract microflora remains
      unclear. Translocation of live bacteria, their metabolic products, or antigens
      from a small bowel colonized by Gram-negative bacilli play a role in the
      pathogenesis of spontaneous bacterial peritonitis in hepatic disease and in
      certain types of sepsis, indicating that further studies can point to new patient
      populations with potential benefit from medical treatment.

PMID- 15855747
TI  - Pathophysiology and impact of enteric bacterial and protozoal infections: new
      approaches to therapy.
AB  - Despite numerous scientific advances in the past few years regarding the
      pathogenesis, diagnostic tools and treatment of infectious enteritis, enteric
      infections remain a serious threat to health worldwide. With globalization of the
      food supply, the increase in travel, mass food processing and antibiotic
      resistance, infectious diarrhea has become a critical concern for both developing
      and developed countries. Oral rehydration therapy has been cited as the most
      important medical discovery of the century due to the millions of lives that have
      been saved. However, statistics concerning diarrhea-induced mortality and the
      highly underestimated morbidity continue to demonstrate the severity of the
      problem. A more complete understanding of the pathogenesis of infectious diarrhea
      and potential new vaccines and effective treatments are badly needed. In
      addition, public health preventive actions, such as early detection of outbreaks,
      care with food, water and sanitation and, where relevant, immunization, should be
      considered a priority. This article provides an overview of the epidemiological
      impact, pathogenesis and new approaches to the management of enteric infections.

PMID- 15855748
TI  - Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential.
AB  - Rifaximin (4-deoxy-4'-methylpyrido[1',2'-1,2]imidazo- [5,4-c]-rifamycin SV) is a
      synthetic antibiotic designed to modify the parent compound, rifamycin, in order
      to achieve low gastrointestinal (GI) absorption while retaining good
      antibacterial activity. Both experimental and clinical pharmacology clearly show
      that this compound is a nonsystemic antibiotic with a broad spectrum of
      antibacterial action covering Gram-positive and Gram-negative organisms, both
      aerobes and anaerobes. Being virtually nonabsorbed, its bioavailability within
      the GI tract is rather high with intraluminal and fecal drug concentrations that
      largely exceed the minimal inhibitory concentration values observed in vitro
      against a wide range of pathogenic organisms. The GI tract represents, therefore,
      the primary therapeutic target and GI infections the main indication. The
      appreciation of the pathogenic role of gut bacteria in several organic and
      functional GI diseases has increasingly broadened its clinical use, which is now
      extended to hepatic encephalopathy, small intestine bacterial overgrowth,
      inflammatory bowel disease and colonic diverticular disease. Potential
      indications include the irritable bowel syndrome and chronic constipation,
      Clostridium difficile infection and bowel preparation before colorectal surgery.
      Because of its antibacterial activity against the microorganism and the lack of
      strains with primary resistance, some preliminary studies have explored the
      rifaximin potential for Helicobacter pylori eradication. Oral administration of
      this drug, by getting rid of enteric bacteria, could also be employed to achieve
      selective bowel decontamination in acute pancreatitis, liver cirrhosis (thus
      preventing spontaneous bacterial peritonitis) and nonsteroidal anti-inflammatory
      drug (NSAID) use (lessening in that way NSAID enteropathy). This antibiotic has,
      therefore, little value outside the enteric area and this will minimize both
      antimicrobial resistance and systemic adverse events. Indeed, the drug proved to
      be safe in all patient populations, including young children. Although rifaximin
      has stood the test of time, it still attracts the attention of both basic
      scientists and clinicians. As a matter of fact, with the advancement of the
      knowledge on microbial-gut interactions in health and disease novel indications
      and new drug regimens are being explored. Besides widening the clinical use, the
      research on rifaximin is also focused on the synthesis of new derivatives and on
      the development of original formulations designed to expand the spectrum of its
      clinical use.

PMID- 15855749
TI  - Rifaximin: in vitro and in vivo antibacterial activity--a review.
AB  - In vitro inhibitory activity of rifaximin is directed against Gram-positive and
      Gram-negative, aerobic and anaerobic bacteria. It is effective in the treatment
      of gastrointestinal infections when given orally because of the high
      concentration of the drug remaining in the gut lumen. Laboratory investigations
      have been carried out to assess the in vitro activity of rifaximin on different
      bacterial strains isolated from both human and domestic animals. The objective of
      this project is to review the in vitro and in vivo activity of rifaximin against
      bacterial infection with Gram-negative rods, Gram-positive rods and Gram-positive
      cocci and their resistance to rifaximin. The available data suggest that
      rifaximin is active in vitro and in vivo in the treatment of bacterial infection
      of adults and children.

PMID- 15855750
TI  - Rifaximin in the treatment of infectious diarrhea.
AB  - Rifaximin matches the criteria for an ideal agent for the treatment of infectious
      diarrhea. It has excellent activity against a broad range of enteropathogens. It
      is nonabsorbable, which may help explain its excellent side effect profile and
      lack of emergence of resistance because of high stool levels that are not likely
      to reach subinhibitory levels before the target Gram-negative bacilli are killed.
      It has shown excellent efficacy in numerous clinical trials of bacterial
      diarrhea. Because of the lack of systemic absorption and minimal adverse
      reactions, rifaximin should be useful in treating hosts such as pregnant women in
      whom the currently favored fluoroquinolones are contraindicated. Uses limited to
      enteric indications and its inherently low propensity to induce sustainable
      resistance among Gram-negative flora favor the sustained usefulness of rifaximin
      in the treatment of enteric infectious syndromes.

PMID- 15855751
TI  - Antibiotic-associated diarrhea and pseudomembranous colitis: are they less common
      with poorly absorbed antimicrobials?
AB  - Diarrhea is a well-known complication of antibiotic therapy. Rates of antibiotic
      associated diarrhea (AAD) vary from 5 to 25%. Some antibiotics are more likely to
      cause diarrhea than others, specifically, those that are broad spectrum and those
      that target anaerobic flora. This paper reviews the effects of antibiotics on the
      fecal flora as well as host factors which contribute to AAD. Clinical features
      and treatment of AAD are also described. Prevention of AAD rests on wise
      antibiotic policies, the use of probiotics and prevention of acquisition in the
      hospital setting. Data from clinical trials suggest that poorly absorbed
      antimicrobials might have a decreased risk of causing AAD and Clostridium
      difficile-associated disease, as concluded from studies of antibiotics used for
      preoperative bowel decontamination and poorly absorbed antibiotics used for
      traveler's diarrhea. Controlled trials would prove this but are not yet
      available. Probiotics may be a good adjunct to poorly absorbed antibiotics to
      minimize the risk of diarrhea associated with antibiotics.

PMID- 15855752
TI  - Management of hepatic encephalopathy: role of rifaximin.
AB  - Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, which develops in
      patients with acute or chronic liver failure. It is widely accepted to be due to
      impairment of hepatic clearance of toxic products from the gut such as ammonia.
      Accumulation of ammonia induces a glutamate neurotoxicity leading to an increased
      tone of the gamma-aminobutyric acid A (GABA-A) receptor system in the brain which
      results in HE. Factors either increasing the ammonia levels (protein load,
      constipation, sepsis, or gastrointestinal bleeding) or potentiating the
      functional activity of the GABAergic system [natural benzodiazepine-like
      compounds (NBZDs) or exogenous benzodiazepines] may act as precipitating factors
      of HE. NBZDs are present in trace amounts in the blood of normal subjects and
      have been found to be increased in the blood of patients with liver cirrhosis,
      with or without HE. These compounds may derive either from the diet since they
      have been found in plants, vegetables and animals or from gut bacteria. The
      observation that intestinal bacterial flora is involved in the production of both
      primary agent of HE (ammonia) and precipitating factors (NBZDs) suggests that the
      use of nonabsorbable antibiotics such as rifaximin may be useful in preventing
      episodes of HE in patients with liver cirrhosis.

PMID- 15855753
TI  - Management of inflammatory bowel disease: does rifaximin offer any promise?
AB  - An increasing number of both clinical and laboratory-derived observations support
      the importance of luminal components in driving the inflammatory response in
      ulcerative colitis and Crohn's disease. Although its role is unclear, antibiotic
      therapy is commonly used in clinical practice for the treatment of moderately to
      severely active ulcerative colitis. Metronidazole and/or ciprofloxacin are
      currently employed in active Crohn's disease, particularly in patients with
      colonic involvement and with perianal disease. Rifaximin, a rifamycin-derived
      antibiotic, is characterized by a wide range of antibacterial activity and a very
      low systemic absorption. Some preliminary data show its efficacy in severe active
      ulcerative colitis, pouchitis and prevention of postoperative recurrence in
      Crohn's disease.

PMID- 15855754
TI  - Treatment of small intestine bacterial overgrowth and related symptoms by
      rifaximin.
AB  - The treatment of small intestine bacterial overgrowth should address different
      aims: the removal of the predisposing condition, guarantee of adequate
      nutritional support to reintegrate both caloric and vitamin requirements and,
      obviously, suppression of the contaminating bacterial flora, which represents the
      major goal. The polymicrobic nature of contaminating flora suggests the
      administration of wide-spectrum antibiotics, but until now there has been no
      conclusive information on the most effective therapeutic approach. In this paper,
      the efficacy of the different therapeutic approaches used is reviewed.

PMID- 15855755
TI  - Management of diverticular disease: is there room for rifaximin?
AB  - Treatment of symptomatic diverticular disease of the colon is aimed at the relief
      of symptoms and the prevention of major complications. The efficacy of fiber
      supplementation and of anticholinergic and spasmolytic agents remains
      controversial. Antibiotics are commonly used in the treatment of inflammatory
      complications of diverticular disease. Data from open labelled and randomized
      controlled trials do suggest the efficacy of rifaximin in obtaining symptomatic
      relief in patients with diverticular disease. Approximately 30% therapeutic gain
      compared to fiber supplementation only can be expected after one year of
      intermittent treatment with rifaximin. Considering the safety and tolerability of
      rifaximin, this drug can be recommended for patients with symptomatic
      uncomplicated diverticular disease.

PMID- 15855756
TI  - Mechanical and antibacterial bowel preparation in colon and rectal surgery.
AB  - Colorectal surgery performed prior to 1970 was fraught with postoperative
      infectious complications which occurred in more than 30-50% of all operations.
      Diversion of the fecal stream appeared mandatory when operating on an urgent or
      emergent basis, thereby requiring the performance of multiple, staged operations
      instead of a single surgery encompassing resection and primary anastomosis as is
      performed commonly today. Multiple studies conducted in the early 1970s
      determined that anaerobic colonic microflora were causative agents in
      postoperative infections in colon and rectal surgery, and these studies initiated
      the development of effective oral preoperative antibiotic prophylaxis in
      combination with preoperative mechanical bowel preparation. This dual-tier
      regimen significantly reduced the incidence of postoperative infectious
      complications, thus allowing most uncomplicated colon and rectal surgeries to be
      performed in a single stage without the need for the diversion of the fecal
      stream and multiple operations. Therefore, a preoperative mechanical and
      antibacterial bowel regimen serves as the cornerstone of modern elective
      colorectal surgery, and these regimens now comprise three therapeutic directives.
      The first step is preoperative mechanical cleansing of the bowel, which is then
      followed by preoperative oral antibiotic prophylaxis. Finally, perioperative
      parenteral antibiotics directed against aerobic and anaerobic colonic microflora
      are utilized.

PMID- 15855757
TI  - Rifaximin, a peculiar rifamycin derivative: established and potential clinical
      use outside the gastrointestinal tract.
AB  - Rifaximin is a poorly absorbed semisynthetic rifamycin derivative with a broad
      spectrum of antibacterial activity including Gram-positive and Gram-negative
      bacteria, both aerobes and anaerobes. Although originally developed for the
      treatment of infectious diarrhea, the appreciation of the pathogenic role of gut
      bacteria in several organic and functional gastrointestinal diseases has
      increasingly broadened its clinical use. The availability of a topical
      formulation (a cream containing 5% of the drug) and the lack of transcutaneous
      absorption pointed out in both animal and human studies has allowed its topical
      use in skin infections. Furthermore, since the spectrum of antibacterial action
      of rifaximin includes many organisms (e.g. Bacteroides bivius-disiens,
      Gardnerella vaginalis, Haemophilus ducreyi) causing genital infections, including
      Trichomonas vaginalis and Chlamydia trachomatis, its local application in the
      treatment of bacterial vaginosis (BV) has been attempted. Finally, since
      periodontal disease, caused by plaque (an aggregate of various bacteria), can be
      considered a 'local' infection, intrapocket rifaximin was tried in the treatment
      of periodontal infections. While the efficacy in pyogenic infections of the skin
      has been confirmed by several investigations, which showed an improvement of both
      subjective and objective parameters significantly better than that of the
      reference drug (i.e. chlortetracycline or oxytetracycline), the usefulness of
      rifaximin in BV and periodontal disease needs to be further studied in well
      designed clinical trials.

PMID- 15855758
TI  - Expression of FoxE4 and Rx visualizes the timing and dynamics of critical
      processes taking place during initial stages of vertebrate eye development.
AB  - Several transcription factors have a critical function during initial stages of
      vertebrate eye formation. In this paper, we discuss the role of the Rx subfamily
      of homeobox-containing genes in retinal development, and the role of the Foxe3
      and FoxE4 subfamily of forkhead box-containing genes in lens development. Rx
      genes are expressed in the initial stages of retinal development and they play a
      critical role in eye formation. Elimination of Rx function in mice results in
      lack of eye formation. Abnormal eye development observed in the mouse mutation
      eyeless (ey1), the medakatemperature-sensitive mutation eyeless (el), and the
      zebrafish mutation chokh are caused by abnormal regulation or function of Rx
      genes. In humans, a mutation in Rx leads to anophthalmia. In contrast, Foxe3 and
      FoxE4 genes are expressed in the lens and they play an essential role in its
      formation. Mutations in the Foxe3 gene are the cause of the mouse mutation
      dysgenetic lens (dyl) and in humans, mutation in FOXE3 leads to anterior segment
      dysgenesis and cataracts. Since Rx and FoxE4 are expressed in the earliest stages
      of retina and lens development, their expression visualizes the timing and
      dynamics of the crucial processes that comprise eye formation. In this paper we
      present a model of eye development based on the expression pattern of these two
      genes.

PMID- 15855759
TI  - The lens has a specific influence on optic nerve and tectum development in the
      blind cavefish Astyanax.
AB  - We used the teleost Astyanaxmexicanus to examine the role of the lens in optic
      nerve and tectum development. This speciesis unusually suited for studies of
      nervous system development and evolution because of its two extant forms: an eyed
      surface dwelling (surface fish) and several blind cave dwelling (cavefish) forms.
      Cavefish embryos initially form eye primordia, but the lens eventually dies by
      apoptosis, then the retina ceases to grow, and finally the degenerating eyes sink
      into the orbits. Transplantation of an embryonic surface fish lens into a
      cavefish optic cup restores eye development. We show here that retinal nerve
      fibers are formed and project to the optic tectum in cavefish embryos. In adult
      cavefish that have completed lens degeneration, however, the number of retinal
      axons in the optic nerve is substantially reduced compared to surface fish. The
      presumptive brain domains of embryonic cavefish are not altered relative to
      surface fish based on expression of the regional marker genes Pax6, Pax2.1, and
      engrailed2. In contrast, the adult cavefish brain is elongated, the optic tectum
      is diminished in volume, and the number of tectal neurons is reduced relative to
      surface fish. Unilateral transplantation of an embryonic surface fish lens into a
      cavefish optic cup increases the size of the optic nerve, the number of
      retinotectal projections from the restored eye, and the volume and neuronal
      content of the contralateral optic tectum. The results suggest that the lens has
      a specific influence on optic nerve and tectum development during eye growth in
      Astyanax.

PMID- 15855760
TI  - The involvement of neural retina pax6 in lens fiber differentiation.
AB  - Proper eye formation depends on specific interactions between neural and
      ectodermal tissues coupled with temporally distinct gene expression and a
      regulated sequence of signaling events. The homeobox gene Pax6 is vitally
      important to the entire process of eye development in both vertebrates and
      invertebrates. Pax6 expression for the retina anlage has been shown to be
      indispensable in the development of various retinal cells. Here, we report that
      Pax6 expression in neural tissue plays an important role in lens development.
      Expression of a dominant-negative version of Pax6 isoform that lacks 5a-exon
      sequence in developing optic vesicles (OV) of chick embryos led to arrest of lens
      development at the lens vesicle stage as well as optic cup deformation. To gain
      insights into the molecular events underlying deformed lens formation, we
      examined the expression of several transcription factors in the lens of Pax6
      negative-OV eye. Importantly, L-Maf was downregulated while c-Maf was found
      normal in deformed lens. We detected a downregulation of fibroblast growth factor
      (FGF8) in the neural tissue. Our in vivo experiments suggest that Pax6 in neural
      retina regulates FGF8 expression, which may maintain L-Maf expression in the lens
      to be essential for later lens fiber differentiation.

PMID- 15855761
TI  - Pax-6 expression in posthatch chick retina during and recovery from form
      deprivation myopia.
AB  - The expression of Pax-6 in fully-differentiated chick retina remains largely
      confined to the amacrine and ganglion cell layers. In the developing posthatch
      chick retina, Pax-6 expression shows a biphasic pattern; a decrease by posthatch
      day 17 followed by a steady increase in the adult eye. Interestingly, we find
      that this biphasic expression of Pax-6 is reflected in the biphasic growth
      pattern of the posthatch chick eye, which is disrupted by form-deprivation myopia
      (FDM). We have now examined the pattern of Pax-6 accumulation in 3-day-old chick
      eyes subjected to 2 weeks of FDM followed by 2 weeks of recovery from FDM.
      Quantitative RT-PCR (with a homologous internal control) revealed that after 2
      weeks of occlusion the contralateral non occluded eyes, the occluded eyes and the
      normal nonexperimental chick eyes did not show any drastic changes in the number
      of Pax-6 transcripts. The data obtained suggests that the contralateral eye does
      not represent a 'normal' control eye; similar but nonidentical changes are seen,
      at the molecular level, in both the contralateral and the occluded eyes.
      Comparisons with the control nonexperimental animals, however, are meaningful.
      Even after 2 weeks of recovery under normal light conditions, the occluded eyes
      do not seem to reach the same level of Pax-6 expression (number of molecules per
      mg tissue) as seen in normal control eyes, suggesting that exposure of the
      posthatch chick eye to FDM impedes developmental progression that normally
      culminates in emmetropia.

PMID- 15855762
TI  - Transplantation of neural progenitor cells into the developing retina of the
      Brazilian opossum: an in vivo system for studying stem/progenitor cell
      plasticity.
AB  - In developing cell transplant strategies to repair the diseased or injured retina
      is essential to consider host-graft interactions and how they may influence the
      outcome of the transplants. In the present study we evaluated the influence of
      the host microenvironment upon neural progenitor cells (NPCs) transplanted into
      the developing and mature retina of the Brazilian opossum, Monodelphis domestica.
      Monodelphis pups are born in an extremely immature state and the neonatal pups
      provide a fetal-like environment in which to study the interactions between host
      tissues and transplanted NPCs. Three different populations of GFP-expressing NPCs
      were transplanted by intraocular injection in hosts ranging in age from 5 days
      postnatal to adult. Extensive survival, differentiation and morphological
      integration of NPCs were observed within the developing retina. These results
      suggest that the age of the host environment can strongly influence NPC
      differentiation and integration.

PMID- 15855763
TI  - The role of hedgehog signaling in the development of the zebrafish visual system.
AB  - The vertebrate visual system is a region of the nervous system that is
      characterized by relative simplicity, and its development has hence been studied
      intensively, to serve as a paradigm for the rest of the central nervous system.
      The zebrafish model organism offers an impressive array of tools to dissect this
      process experimentally, and in recent years has helped to significantly deepen
      our understanding of the development of the visual system. A number of these
      studies have focused on the role of the Hedgehog family of secreted signaling
      molecules in eye development, and this is the main topic of this review. Hedgehog
      signaling plays an important role in all major steps of visual system
      development, starting with the regionalization of the eye primordium into
      proximal and distal territories, continuing with the control of cellular
      differentiation in the retina, and ending with the guidance of axonal projections
      from the retina to the optic centers of the brain.

PMID- 15855764
TI  - Wnt/frizzled signaling during vertebrate retinal development.
AB  - Multiple signaling pathways are known to be involved in regulating development of
      the vertebrate neural retina. Recent publications have demonstrated that
      Wnt/Frizzled (Fz) signaling components are expressed in the developing retina and
      may play a fundamental role in retinogenesis. In this review, we summarize Wnt/Fz
      expression patterns in the developing vertebrate retina, mainly from chick and
      mouse, and compare them with Wnt/beta-catenin reporter activity. Consistent with
      the dynamic expression patterns of Wnt pathway components, evidence suggests that
      Wnt/Fz signaling has multiple roles during retinal development.

PMID- 15855765
TI  - Ciliary neurotrophic factor promotes muller glia differentiation from the
      postnatal retinal progenitor pool.
AB  - Ciliary neurotrophic factor (CNTF) exhibits multiple biological effects during
      vertebrate retinal development, including regulating the differentiation of
      photoreceptor cells and promoting the survival and axonal growth of ganglion
      cells. We report here that in addition to affecting the differentiation of
      retinal neurons, CNTF also promotes Muller glia genesis in the postnatal mouse
      retina. In both retinal monolayer and explant cultures, CNTF increases the number
      of progenitor cells adopting the Muller cell fate. Exogenous CNTF induces
      phosphorylation of signal transducers and activators of transcription (STAT)3 and
      extracellular signal-regulated kinase (ERK) among neonatal progenitor cells and
      newborn Muller cells. In addition, increased levels of endogenous STAT3 and ERK
      phosphorylation have been observed at around postnatal day 5, coinciding with the
      peak of Muller glia genesis. Perturbation of STAT and ERK signaling using protein
      kinase inhibitors and a dominant-negative STAT3 mutant demonstrates that both
      CNTF-induced STAT and ERK activation are involved in promoting Muller cell
      production. Moreover, absorbing epidermal growth factor (EGF) signals with a
      neutralizing antibody did not affect CNTF-induced Muller glial genesis,
      indicating that the effect of CNTF is not mediated by the known Muller-enhancing
      activity of EGF. Together, these results support a novel function of CNTF-like
      cytokines in retinal gliogenesis.

PMID- 15855766
TI  - MARCKS in advanced stages of neural retina histogenesis.
AB  - Myristoylated alanine-rich kinase C substrate (MARCKS), an actin-binding protein,
      is involved in several signal transduction pathways. It is susceptible to be
      phosphorylated by protein kinases as protein kinase C and some proline-directed
      kinases. These phosphorylations differently modulate its functions. We previously
      showed that a phosphorylation at its Ser25 (S25p-MARCKS) in chickens is a
      signature of this ubiquitous protein in neuron differentiation. To gain insight
      into the possible involvement of MARCKS in late retinal histogenesis, we compared
      the developmental expression patterns of the total protein and its S25p variants.
      Here we show that the most outstanding modifications occur at the outer retina,
      where S25p disappears at the end of embryonic development and where MARCKS is
      missing in adults. These results suggest diverse functional specializations in
      the different retinal layers.

PMID- 15855767
TI  - 5A11/Basigin gene products are necessary for proper maturation and function of
      the retina.
AB  - 5A11/Basigin gene products are important membrane glycoproteins for development
      and maturation of the retina. The gene encodes two immunoglobulin-like, membrane
      bound glycoproteins as a result of splice variation. The smaller protein product,
      named 5A11/Basigin, is expressed by many tissues within the mouse, whereas the
      larger protein product, named 5A11/Basigin-2, is expressed only by the
      photoreceptor cells (PCs) of the retina. Mice in which the gene for 5A11/Basigin
      has been deleted have several abnormalities, including blindness from the time of
      eye opening with subsequent degeneration of the PCs. Studies by this laboratory
      suggest that a developmental deficiency is the underlying cause of the blindness.
      However, definitive biological functions for 5A11/Basigin and 5A11/Basigin-2 have
      yet to be defined. It is known that 5A11/Basigin is multifunctional and can
      interact with several different proteins. Preliminary studies indicate that
      5A11/Basigin-2 may be multifunctional as well. Studies by this laboratory and
      others have demonstrated that 5A11/Basigin (and probably 5A11/Basigin-2) acts as
      a chaperone for monocarboxylate transporter-1 (MCT-1) translocation to the cell
      membrane. We have proposed that a lactate metabolon exists within the retina and
      functions to shuttle lactate, an energy source, from glial cells to the PCs. This
      metabolon is not present within 5A11/Basigin null mouse retinas, which may be the
      underlying cause of the retinal dysfunction and subsequent degeneration. Further
      studies will be necessary to determine which of the functions are critical for
      proper development of the retina.

PMID- 15855768
TI  - 'One receptor' rules in sensory neurons.
AB  - With the recent explosion in the characterization of different sensory systems, a
      general rule is emerging: only one type of sensory receptor molecule is expressed
      per receptor neuron. The visual system is no exception and, in most cases,
      photoreceptors express only one visual pigment per cell. However, the mechanisms
      underlying the exclusion of sensory receptors are poorly understood. As
      expression of a given receptor in a given cell is often stochastic, a decision
      must first be made to express one of the many receptors of the same family (i.e.
      one particular rhodopsin) and this expression must correlate with the silencing
      of the other receptors. Furthermore, the projection center for the receptors in
      the brain must be informed of the decision in order to process this information.
      Although cells can choose from up to hundreds of sensory receptors (e.g. in the
      olfactory system), they make almost no mistakes. Evidence has recently emerged
      that the exclusion mechanism involves the sensory receptor molecules themselves.
      Here, we describe the findings from various systems in mammals and Drosophila,
      and review evidence that in the simple visual system of the fly, rhodopsin
      molecules play an important role in sensory receptor exclusion.

PMID- 15855769
TI  - Long-term treatment of the developing retina with the metabotropic glutamate
      agonist APB induces long-term changes in the stratification of retinal ganglion
      cell dendrites.
AB  - The gradual restriction of initially multistratified retinal ganglion cell (RGC)
      dendrites into ON and OFF sublaminae of the inner plexiform layer (IPL) can be
      effectively blocked by treating the developing retina with 2-amino-4
      phosphonobutyrate (APB), the metabotropic glutamate agonist, or by light
      deprivation. Previous studies have focused on the short-term consequences of such
      manipulations, so the long-term effects of arresting dendritic stratification on
      the structural development of RGCs are as yet unknown. In the present study, we
      have addressed this issue by performing a morphological analysis of alpha RGCs
      labeled by retrograde transport of horseradish peroxidase injected into the
      dorsal lateral geniculate nucleus of adult cats that received monocular
      injections of APB from postnatal (P) day 2 until P30. A large proportion of the
      alpha cells in the APB-treated eye (44%) were found to have multistratified
      dendrites that terminated in both the ON and OFF sublaminae of the IPL. The
      dendritic arborization pattern in the sublaminae of the IPL of these cells was
      asymmetric, showing a variety of forms. Immunolabeling of retinal cross-sections
      showed that mGLUR6 receptors appeared normal in density and location, while
      qualitative observation suggested an increase in the axonal arborization of rod
      bipolar cells. These findings indicate that long-term treatment of the neonatal
      retina with APB induces a long- lasting structural reorganization in retinal
      circuitry that most likely accounts for some of the previously described changes
      in the functional properties of RGCs.

PMID- 15855770
TI  - Emergence of realistic retinal networks in culture promoted by the superior
      colliculus.
AB  - The developing retina is characterized by 'retinal waves', spontaneous
      depolarizations that propagate through a developing network of interneurons and
      retinal ganglion cells. Although the circuitry underlying retinal waves is well
      characterized, the secreted factors that are critical for its normal development
      are not defined. Dissociated cell culture provides an ideal system for defining
      these factors; however, it is difficult to recapitulate retinal circuitry in
      culture. Here we demonstrate that by culturing dissociated retinal neurons in the
      presence of cells from the superior colliculus (SC), retinal neurons form
      networks that are similar to those described in the intact retina. Whole-cell
      voltage clamp recordings reveal the presence of a spontaneously active network of
      interneurons. In addition, we observed spontaneous, propagating activity
      reminiscent of that observed in the intact retina. We propose that the presence
      of factors secreted from the SC results in the development of networks that
      reproduce critical features of the intact retina.

PMID- 15855771
TI  - The RB protein family in retinal development and retinoblastoma: new insights
      from new mouse models.
AB  - The Rb gene was isolated almost 20 years ago, but fundamental questions regarding
      its role in retinal development and retinoblastoma remain. What is the normal
      function of RB protein in retinogenesis? What is the cell-of-origin of
      retinoblastoma? Why do retinoblastoma tumors have recurrent genetic lesions other
      than Rb inactivation? Why is retinoblastoma not induced by defects in cell cycle
      regulators other than Rb? Why is the retina so sensitive to Rb loss? Recently
      developed conditional Rb knockout models provide new insight into some of these
      issues. The data suggest that RB protein may not control the rate of progenitor
      division, but is critical for cell cycle exit when dividing retinal progenitors
      differentiate into postmitotic transition cells. This finding focuses attention
      on the ectopically dividing transition cell, rather than the progenitor, as the
      cell-of-origin. Cell-specific analyses in the RB-deficient retina reveal that
      ectopically dividing photoreceptors, bipolar and ganglion cells die, but
      amacrine, horizontal and Muller cells survive and stop dividing when they
      terminally differentiate. Rare amacrine transition cells escape cell cycle exit
      and generate tumors. These data suggest that post-Rb mutations are required to
      overcome growth arrest associated with terminal differentiation, rather than
      apoptosis as previously suggested. To explain why perturbing cell cycle
      regulators other than RB does not initiate retinoblastoma, we speculate that
      mutations in other components of the RB pathway perturb cell cycle arrest, but
      only RB loss triggers genome instability in retinal transition cells, which may
      be critical to facilitate post-Rb mutations necessary for transformation. Cell
      specific differences in the effect of Rb loss on genome stability may contribute
      to the tremendous sensitivity of retinal transition cells to tumorigenesis. The
      new mouse models of retinoblastoma will be invaluable for testing these
      possibilities.

PMID- 15855772
TI  - Distinct capacities of individual E2Fs to induce cell cycle re-entry in
      postmitotic lens fiber cells of transgenic mice.
AB  - PURPOSE: Inactivation of the retinoblastoma gene in human retinoblasts or mouse
      lens fiber cells causes inappropriate cell cycle entry, presumably as a
      consequence of elevated activity of the E2F transcription factors. Although E2Fs
      are known to be critical regulators of the cell cycle, it is still unclear
      whether family members E2F3a, E2F4 or E2F5 are individually capable of inducing
      cell cycle entry in vivo. In this study, we designed experiments to test whether
      lens-specific expression of these E2F family members would induce postmitotic
      fiber cells to re-enter the cell cycle. METHODS: Transgenic mice were generated
      by microinjection of constructs that contained E2F cDNAs (E2F3a, E2F4 or E2F5)
      linked to the mouse lens-specific alphaA-crystallin promoter. The mice were
      characterized by histology, in situ hybridization, immunohistochemistry, BrdU
      incorporation, TUNEL assay and Western blots. RESULTS: E2F3a expression was
      sufficient to induce cell cycle entry in lens fiber cells. Cell cycle re-entry
      was accompanied by apoptotic cell death resulting in microphthalmia. E2F4
      expression stimulated a modest level of cell cycle re-entry, but the transgenic
      lenses remained normal in size and did not show significant apoptosis. Transgenic
      mice expressing E2F5 did not show lens defects. In both the E2F3a and E2F4
      transgenic lenses, cyclin A2 and cyclin B1 expression were upregulated.
      Phosphorylated histone H3, a marker for mitosis, was detected in the E2F3a fiber
      cells. Western blots showed that both p53 and p73alpha were upregulated in the
      E2F3a lenses. However, expression of p21, a well-known p53 target gene, was not
      activated, suggesting that p73alpha might be responsible for inducing apoptosis
      and blocking unregulated proliferation in lens cells overexpressing E2F3a.
      CONCLUSIONS: E2F3a and E2F4, but not E2F5, function to induce cell cycle entry,
      although E2F4 has more modest activity. E2F3a may induce cell death primarily
      through activation of p73alpha.

PMID- 15855773
TI  - Deregulation of lens epithelial cell proliferation and differentiation during the
      development of TGFbeta-induced anterior subcapsular cataract.
AB  - Normal lens development and growth is dependent on the tight spatial and temporal
      regulation of lens cell proliferation and fiber cell differentiation. The present
      study reports that these same cellular processes contribute to lens pathology as
      they become deregulated in the process of anterior subcapsular cataract
      development in a transgenic mouse model. During the formation and growth of
      transforming growth factor (TGF)beta-induced subcapsular plaques, lens epithelial
      cells lose key phenotypic markers including E-cadherin and connexin 43, they
      multilayer and subsequently differentiate into myofibroblastic and/or fiber-like
      cells. Growth of the subcapsular plaques in the transgenic mouse is sustained by
      an ordered process of cell proliferation, exit from the cell cycle and
      differentiation. As reiterating ordered growth and differentiation patterns is
      atypical of the direct effects of TGFbeta on lens cells in vitro, we propose that
      other growth factors in the eye, namely fibroblast growth factor, may also play a
      role in the establishment and regulation of the key cellular processes leading to
      lens pathology. Obtaining a better understanding of the molecular aspects and
      cellular dynamics of cataract formation and growth is central to devising
      strategies for slowing or preventing this disease.

PMID- 15855774
TI  - Looking at an oft-overlooked part of the eye: a new perspective on ciliary body
      development in chick.
AB  - The ciliary body is an essential tissue for the development and homeostasis of
      the vertebrate eye. Embryonically, the epithelial portion of the ciliary body
      derives from the neuroepithelium of the optic cup, however, it differentiates
      into a secretory tissue and produces an aqueous humor that sustains the lens and
      cornea, and maintains the requisite pressure within the orb. The unique
      differentiation of this portion of the optic cup is little understood. This
      article reviews what is known about the development of the ciliary body and
      presents some preliminary findings that may lead to a new model for the formation
      of the ciliary body.

PMID- 15855775
TI  - A case of Hashimoto's encephalopathy with demyelinating peripheral neuropathy.

PMID- 15855776
TI  - Severe oxygen desaturation in obstructive sleep-apnea syndrome as a possible
      cause of ischemic stroke.

PMID- 15855777
TI  - Foreign accent following brain injury: syndrome or epiphenomenon?

PMID- 15855778
TI  - Primary stabbing headache with buccal triggers.

PMID- 15855779
TI  - Hemihypomimia in Parkinson's disease.

PMID- 15855780
TI  - Reversible visual deficit and Corpus callosum lesions due to metronidazole
      toxicity.

PMID- 15855781
TI  - Posterior fossa tremor induced by HIV-associated progressive multifocal
      leukoencephalopathy.

PMID- 15855782
TI  - Hashimoto encephalopathy and neuralgic amyotrophy--causal link or chance
      association?

PMID- 15855783
TI  - Association analysis of adenosine A2a receptor 1976T>C polymorphisms and
      Alzheimer's disease.

PMID- 15855784
TI  - HIV-associated multiple intracerebral hemorrhages.

PMID- 15855785
TI  - A note on bent spines: 'camptocormia' and 'head ptosis'.

PMID- 15855786
TI  - Paraneoplastic limbic encephalitis.

PMID- 15855787
TI  - Migraine.

PMID- 15855788
TI  - Hemianopia.

PMID- 15855789
TI  - The relative efficiency of penetrance estimators for sib pairs.
AB  - Here we present analytical studies to evaluate the relative efficiency of
      commonly used penetrance estimators using linkage designs. We investigated three
      different methods of estimating penetrance using sib pairs: Maximum likehood
      estimation (MLE) with trait information alone, MLE with both trait and marker
      information and the MOD score approach. Modeling sib pairs with unknown phase, we
      evaluated the asymptotic relative efficiency between estimators under either
      random sampling or single ascertainment for an autosomal dominant or recessive
      disease. We then provide plots of the asymptotic relative efficiency, enabling
      researchers to easily determine regions where the MOD score or segregation alone
      performs with comparable efficiency relative to joint segregation and linkage.

PMID- 15855791
TI  - A comparative study of the FcepsilonRI molecule on human mast cell and basophil
      cell lines.
AB  - BACKGROUND: Mast cells and basophils express the high-affinity IgE receptor
      FcepsilonRI. We have analysed the human mast cell line LAD2 and four subclones of
      the basophil cell line KU812 in order to reveal possible differences concerning
      the FcepsilonRI surface regulation, anti-IgE-triggered activation,
      FcepsilonRIalpha protein stability and the mRNA level of FcepsilonRIalpha-, beta-
      and the truncated beta-chain (beta(T)), and thereby determine the utility of
      these cell lines in investigations of the FcepsilonRI biology. METHODS: The
      surface expression of FcepsilonRI was assessed by flow cytometry, using the
      monoclonal antibody CRA1. The FcepsilonRI-induced cellular activation (i.e. cross
      linking of FcepsilonRI) was determined by changes in the intracellular level of
      Ca2+, which was measured by fluorescence of Fura-2. The level of the
      FcepsilonRIalpha protein was determined by a Western blot technique and by a
      radioimmunoassay. The mRNA level of FcepsilonRIalpha, beta- and beta(T)-chain was
      analysed using real-time PCR. RESULTS: Two KU812 subclones and especially LAD2
      had FcepsilonRI surface expression which was capable of inducing cellular
      activation. Both the FcepsilonRI expression and stability of the FcepsilonRIalpha
      protein were increased when IgE was present. All the cell lines expressed mRNA of
      FcepsilonRIalpha-, beta- and beta(T), with LAD2 tending to have the highest
      expression. However, a determination of the beta/beta(T) ratio demonstrated no
      difference between any of the cell clones. CONCLUSION: These cell lines are
      important tools in the investigation of both the FcepsilonRI molecule and the
      effects induced by its activation.

PMID- 15855792
TI  - Peroxynitrite modulates release of inflammatory mediators from guinea pig lung
      mast cells activated by antigen-antibody reaction.
AB  - BACKGROUND: Peroxynitrite (ONOO-), the product of the reaction between the
      superoxide anion (*O2-) and nitric oxide (NO), is produced during inflammatory
      disease and may be a major cytotoxic agent. No reports are available as to
      whether ONOO- generates or modulates inflammatory mediator release from activated
      guinea pig lung mast cells. In this study, we explored the modulatory role of
      intracellular ONOO- on inflammatory mediator release (histamine and leukotrienes)
      from activated mast cells. METHODS: Guinea pig lung mast cells were purified by
      the enzyme digestion, and by using the rough and discontinuous Percoll density
      gradients. Mast cells were sensitized with IgG1 (anti-ovalbumin) antibody and
      challenged with ovalbumin (OVA). The intracellular ROS formation was determined
      by following the oxidative production of 2', 7'-dichlorofluorescein diacetate
      (DCFH-DA), dihydrorhodamine 123 (DHR), and anti-nitrotyrosine antibody
      immunofluorescence. Histamine was assayed using a fluorometric analyzer,
      leukotrienes by radioimmunoassay, intracellular Ca2+ levels by confocal scanning
      microscopy, and PLA(2) activity using prelabeling of [3H]arachidonic acid.
      RESULTS: ROS detected by DCFH-DA weakly increased in mast cells activated with
      OVA (1.0 g/ml), and the ROS so generated was inhibited by ebselen (50 microM).
      However, the ROS detected by DHR increased 3-fold under the same conditions.
      Peroxynitrite scavengers sL-MT, DMTU, and inhibitor FeTPPS inhibited ROS
      formation but the NADPH oxidase inhibitor diphenyleneiodonium (DPI) only
      partially inhibited this formation. Dimethyl thiourea (DMTU) and seleno-L
      methionine (sL-MT) inhibited the tyrosine nitration of cytosolic proteins, the
      release of histamine and leukotrienes, Ca2+ influx, and the PLA(2) activity
      evoked by mast cell activation. CONCLUSION: The data obtained suggests that the
      ROS generated by the antigen/antibody reaction activated mast cells is ONOO-, and
      that this modulates the release of inflammatory mediators via Ca2+ -dependent
      PLA(2) activity.

PMID- 15855793
TI  - Delayed-type asthmatic response induced by repeated intratracheal exposure to
      toluene-2,4-diisocyanate in guinea pigs.
AB  - BACKGROUND: A toluene-2,4-diisocyanate (TDI)-induced asthma model, in which
      delayed-type hypersensitivity-like asthmatic airway obstruction is elicited
      restrictively in the lung, has never been developed. METHODS: Guinea pigs were
      percutaneously sensitized with TDI. For the challenges, once every 2 weeks for a
      total of 5 times, TDI mists were delivered directly to the lung through an oral
      cannula, with its tip being positioned in the opening of the trachea. Time-course
      changes in specific airway resistance (sRaw) were measured by double-flow
      plethysmography. Basic mechanisms underlying TDI-induced asthma were analyzed.
      RESULTS: After the 2nd-5th challenges, induction of both an early increase in
      sRaw that peaked at 10 min and a delayed-type sRaw elevation that peaked at 22 h
      were observed. Interestingly, in the sensitized/challenged animals, baseline sRaw
      was elevated by repeated challenge as compared to that seen for non-sensitized
      animals. Intratracheal administration of a bronchodilator, salbutamol, strongly
      suppressed the early asthmatic response (EAR) but not the delayed-type asthmatic
      response (DAR). During DAR, both albumin leakage and fucose secretion into the
      bronchoalveolar lavage fluid were increased. The cysteinyl leukotriene antagonist
      pranlukast failed to inhibit either EAR or DAR while the corticosteroid
      dexamethasone significantly suppressed DAR, without significantly affecting EAR.
      CONCLUSIONS: Effective delivery of TDI to the lung may induce reproducible DAR in
      sensitized guinea pigs with chronicity that is reflected by an increase in the
      sRaw baseline. DAR is not mediated by constriction of airway smooth muscles and
      is probably due to the concurrent presence of mucosal edema and mucus
      hypersecretion in the airways.

PMID- 15855794
TI  - Prominent involvement of activated Th1-subset of T-cells and increased expression
      of receptor for IFN-gamma on keratinocytes in atopic dermatitis acute skin
      lesions.
AB  - BACKGROUND: Atopic dermatitis (AD) is an allergic skin disease mediated by
      antigen-specific IgE and an important role has been ascribed to CD4+ cells (Th
      cells). The objective of the study was to evaluate humoral and cellular
      immunological factors in the blood and the skin lesions of AD patients, and to
      analyze the presence of inflammatory cell-surface markers in blood and skin
      biopsies. METHODS: The parameters for monitoring of 40 AD patients included
      results of prick test to inhalant allergens and epicutaneous (patch) test to
      contact allergens; values of total IgE, serum immunoglobulins (IgG, IgA, IgM) and
      different cell markers in the sera (CD3, CD4, CD8, CD20, CD21, CD23, HLA-DR). We
      also analyzed the presence of inflammatory cell-surface markers (CD3, CD4, CD8,
      CD20, CD20, CD1a, CD23, CD29, CD45Ro, IFNgamma+ markers) in the biopsies of skin
      lesions from 10 AD patients and 5 healthy controls (HCs) by immunohistochemical
      analysis (method of avidin-biotin immunoperoxidase). RESULTS: Beside increased
      total serum IgE and positive skin tests, a significantly higher percentage of
      CD23+ cells with lower percentage of CD21+ cells was revealed in peripheral blood
      of AD patients in comparison to HCs. A positive epidermal expression of the
      majority of markers of T cells (CD3+, CD4+, CD8+, CD29+, CD45Ro+, IFNgamma+) and
      those of Langerhans' cells (LCs) (CD1a, CD23+), without those of B cells (CD20+)
      were noted in AD patients, but no in the skin of HCs. Furthermore, significant
      difference was also found between the two groups for increased expression of CD3,
      CD4, CD8, CD29, CD45Ro, IFNgamma+ markers (markers for IFNgamma receptor) and
      higher intraepidermal CD23+ LCs and intradermal CD1a+ LCs in AD skin lesions.
      CONCLUSIONS: The obtained results suggest involvement of various humoral factors
      with increased production of IgE and cooperation between Th subsets and LCs, with
      higher production of related cytokines, and disturbed cellular immunity,
      including epidermal LCs with IgE receptors of high and low affinity in AD. The
      annotation of activated Th1 cells with increased producing of IFNgamma in acute
      AD skin lesions is notable, and might lead to IFNgamma binding to keratinocytes
      and consequently inflammatory skin changes in the disease.

PMID- 15855795
TI  - Reduced arteriolar responses to skeletal muscle contraction after ingestion of a
      high salt diet.
AB  - We previously reported that in skeletal muscle arterioles of rats fed a very high
      salt (HS; 7%) diet, the bioavailability of endothelium-derived nitric oxide (NO)
      is reduced through scavenging by reactive oxygen species. Because arteriolar NO
      can play an important role in local blood flow control, we investigated whether
      arteriolar responses to increased tissue metabolism become compromised in
      skeletal muscle of salt-fed rats. Consumption of a HS (4%) diet for 4 weeks had
      no effect on arteriolar diameters, volume flow or shear stress in resting
      spinotrapezius muscle. Arteriolar responses to a modest elevation in metabolic
      demand (0.5 Hz contraction) were not different from those in rats fed a normal
      diet, but diameter responses to a greater elevation in metabolic demand (4 Hz
      contraction) were significantly less in HS rats than in rats fed a normal diet.
      In both groups, the NO synthase inhibitor N(G)-monomethyl-L-arginine reduced
      resting arteriolar diameters and flow by a similar amount and had little or no
      effect on arteriolar diameter or flow responses to muscle contraction. Arterioles
      in HS rats exhibited an increase in overall oxidant activity (tetranitroblue
      tetrazolium reduction) but not in superoxide activity (dihydroethidine
      oxidation). Reactive oxygen species scavengers (2,2,6,6-tetramethylpiperidine-N
      oxyl and catalase) did not normalize the reduced arteriolar responses to muscle
      contraction in HS rats. These findings suggest that increased oxidant activity in
      the arteriolar network of salt-fed rats is not due to accumulation of superoxide
      anion and that neither this oxidant activity nor reduced NO availability can
      account for the blunted active arteriolar dilation in rats fed a 4% salt diet.

PMID- 15855796
TI  - Interferon therapy in hemodialysis patients with chronic hepatitis C: study of
      tolerance, efficacy and post-transplantation course.
AB  - BACKGROUND: The potential benefit of pre-transplant treatment of chronic
      hepatitis C on long-term evolution after renal transplantation is not clear.
      METHODS: Fifty successive renal transplant candidates had their sera positive for
      HCV RNA and a biopsy-proven chronic hepatitis. Out of these, 18 patients received
      a standard course of interferon-alpha2b (IFN; 3 MU three times weekly after
      hemodialysis sessions for 6 months). RESULTS: IFN was discontinued in 2 patients
      (11%) due to persistent leukopenia. HCV RNA turned negative in 10 patients of the
      treatment group and in none of the control group. Two patients of the IFN group
      had a virological relapse post-transplantation. Post-transplant follow-up periods
      were 41.5 +/- 15 and 50 +/- 16 months for the treated and control groups
      respectively. Transaminases remained normal in all patients of the IFN group
      after transplantation. In contrast, biochemical evidence of acute and chronic
      hepatitis was observed in 5 (p = 0.03) and 13 (p = 0.002) patients, respectively,
      of the control group. Logistic regression analysis identified non-receiving IFN
      before transplantation as a risk factor for post-transplant hepatic dysfunction
      (odds ratio = 11.7, p = 0.003) and for chronic allograft nephropathy (odds ratio
      = 11.6, p = 0.02). CONCLUSIONS: IFN-treated patients had a significantly better
      post-transplant hepatic function and significantly lower rates of chronic
      allograft nephropathy.

PMID- 15855797
TI  - Clinical significance of C-reactive protein in patients on hemodialysis: a
      longitudinal study.
AB  - BACKGROUND/AIM: The levels of C-reactive protein (CRP) have been related to
      hypoalbuminemia and the necessity of erythropoietin in patients on maintenance
      hemodialysis. However, in several studies, the patients' clinical situation is
      not taken into account. The aim of the present work was to analyze the
      relationship between CRP and serum albumin and hemoglobin and the erythropoietin
      resistance index (ERI) in a population of patients on chronic hemodialysis
      classified according to their clinical situation. METHODS: In a cohort of 53
      patients followed for 12 months, we analyzed the CRP level and its association
      with albumin and hemoglobin levels and the ERI (ratio of total weekly
      erythropoietin dose in units/weight to hemoglobin concentration in g/dl) at the
      start of the study and at 6 and 12 months thereafter. The patients were divided
      into three groups based on the presence of inflammatory/infectious disorders
      during the 4 weeks prior to CRP determination (group A) or the use of a jugular
      catheter (group B) or an arteriovenous fistula (group C) as vascular access for
      hemodialysis. RESULTS: At baseline, the CRP levels (47.1 mg/l in group A, 30.7
      mg/l in group B, and 9.4 mg/l in group C) and the ERI (23.9 in group A, 24.6 in
      group B, and 10.7 in group C) were higher in groups A and B than in group C (p <
      0.001 for both parameters). Serum albumin (3.9 g/dl in group A, 4.1 g/dl in group
      B, and 4.4 g/dl in group C) and hemoglobin (10.4 g/dl in group A, 11.3 g/dl in
      group B, and 12 g/dl in group C) were lower in groups A and B than in group C (p
      < 0.05 for serum albumin and p < 0.01 for hemoglobin). In all patients, the
      baseline CRP level correlated with the albumin level (r = -0.3853, p < 0.01),
      with the hemoglobin level (r = -0.2950, p < 0.05), and with the ERI (r = 0.4378,
      p < 0.01). However, if we only considered the group C patients, there was no
      correlation between baseline CRP and albumin, hemoglobin, and ERI. Similar
      results were observed at 6 and 12 months. CONCLUSIONS: The CRP, albumin, and
      hemoglobin levels and the ERI mostly depend on the existence of ongoing
      inflammatory/infectious disorders and the use of a catheter as vascular access.
      In the absence of these clinical conditions, we could not correlate the CRP level
      with the other parameters. The relationship between CRP, albumin, and anemia may
      be an epiphenomenon.

PMID- 15855798
TI  - Two-stage community-based screening model for estimating prevalence of diabetic
      polyneuropathy (KCIS no. 6).
AB  - The aim of this study was to apply a calibrated two-stage community-based design
      to estimate the prevalence of diabetic distal sensorimotor polyneuropathy (DPN)
      in Taiwan. Type 2 diabetics were identified from a population-based screening
      program in Keelung, Taiwan. Administration of the Neurological Symptom Score
      (NSS) questionnaire identified 210 DPN-positive cases of the 587 diabetic
      subjects tested. The accuracy of this NSS screening was tested with sensitive
      electrophysiological DPN diagnosis. A smaller validation study was also conducted
      to estimate the sensitivity and specificity of the NSS questionnaire. In the
      validation study, the overall prevalence rate for DPN among type 2 diabetics was
      26.79%. The sensitivity, specificity, positive predictive value and negative
      predictive values were 73.33, 30.49, 24.72 and 75.76%, respectively. The
      estimates of sensitivity, specificity and positive predictive values were 75.00,
      33.33 and 42.86% for old cases of diabetes, and 72.22, 29.69 and 22.41% for newly
      diagnosed cases. The range of prevalence rate in the main study was adjusted to
      28.46-36.30% after calibration for sensitivity and specificity with the
      validation study data. A two-stage community-based screening model with
      calibration of prevalence rate was developed and enabled a cost-effective DPN
      prevalence rate estimate in a study with a large number of subjects.

PMID- 15855799
TI  - Early life socioeconomic status and late life risk of Alzheimer's disease.
AB  - The authors examined the relation of early life socioeconomic status to incident
      Alzheimer's disease (AD), level of cognition and rate of cognitive decline in old
      age. For up to 10 years, 859 older Catholic clergy members without dementia at
      baseline completed annual clinical evaluations as part of the Religious Orders
      Study. The evaluations included clinical classification of AD and detailed
      cognitive testing. At baseline, indicators of early life household socioeconomic
      level (e.g., parental education) and the county of birth were ascertained.
      Socioeconomic features of the birth county (e.g., literacy rate) were estimated
      with data from the 1920 US Census. Composite measures of early life household and
      community socioeconomic level were developed. In analyses that controlled for
      age, sex and education, higher household and community socioeconomic levels in
      early life were associated with higher level of cognition in late life but not
      with risk of AD or rate of cognitive decline. The results suggest that early life
      socioeconomic level is related to level of cognition in late life but not to rate
      of cognitive decline or risk of AD.

PMID- 15855800
TI  - Disability and mortality in a cohort of multiple sclerosis patients: a
      reappraisal.
AB  - The aim of the study was to evaluate how the natural history of multiple
      sclerosis (MS) had changed over a 15-year period. We compared disability and
      mortality in a cohort of 83 MS patients hospitalised in the Neurological
      Institute of Pavia, northern Italy, from January 1, 1990, to December 31, 1991,
      with a similar cohort of 52 patients analysed in the past. After the follow-up,
      an unfavourable course (death or relevant disability) was observed in 41% of the
      patients in the new cohort, compared to 63.5% of the patients in the old one. The
      percentage of deceased patients was reduced from 25 to 6%. The analysis of the
      pooled data of the two cohorts indicates a recent tendency of firstly
      hospitalised patients having a shorter disease duration and a lower disability
      level, which could explain the relevant decrease both in mortality and
      disability. Finally, our findings confirmed that age at onset, early disability
      and a short interval between onset and secondary progression increase the risk of
      an unfavourable course.

PMID- 15855801
TI  - Assessment of cognitive decline in old age with brief tests amenable to telephone
      administration.
AB  - The adequacy with which brief cognitive tests suitable for telephone
      administration can assess cognitive decline due to aging and Alzheimer's disease
      is uncertain. The authors examined these issues with data from the Religious
      Orders Study, which involves annual clinical evaluations and brain donation at
      death. Participants are 996 older Catholic clergy members. Analyses focused on
      seven cognitive tests which can be administered in person or by telephone in less
      than 15 min. Composite measures of global cognition and of episodic, semantic and
      working memory were formed. During a mean of 5.8 years of follow-up, performance
      on each composite measure declined in persons with and without dementia at
      baseline. Among those without dementia, possession of the apolipoprotein E
      epsilon4 allele was associated with more rapid cognitive decline, especially in
      episodic and working memory. Level of performance on each cognitive measure
      proximate to death was inversely related to the level of cortical plaques and
      tangles in the brain. In a subset of persons who were given the tests by
      telephone, there was no evidence that performance differed from in-person
      administration. The results suggest that briefly assessing cognition with tests
      amenable to telephone administration may prove useful in longitudinal
      epidemiologic studies of older persons.

PMID- 15855802
TI  - Risk of hemorrhagic stroke in Asian American ethnic groups.
AB  - The sparseness of prospective data about hemorrhagic stroke (HS) risk among Asian
      American ethnic groups led to the investigation of 128,934 persons with self
      classified ethnicity at health examinations in 1978-1985. Subsequently, 431
      persons were hospitalized for HS; 31% for subarachnoid hemorrhage (SAH) and 69%
      for intracerebral hemorrhage (ICH). Ethnic predictors of HS were studied by Cox
      proportional hazard models with 7 covariates. With whites as reference, the
      adjusted relative risk (95% CI) of all Asians for HS was 1.6 (1.1-2.3, p = 0.01),
      due substantially to increased risks of SAH in Japanese people and ICH in
      Filipinos. These data mandate emphasis upon preventive measures in these groups.

PMID- 15855803
TI  - A survey of the SWISS researchers on the impact of sibling privacy protections on
      pedigree recruitment.
AB  - To understand the perceptions and attitudes about privacy safeguards in research
      and investigate the impact of letter-based proband-initiated contact on
      recruitment, we surveyed researchers in the Siblings With Ischemic Stroke Study
      (SWISS). All 49 actively recruiting sites provided at least 1 response, and 61%
      reported that potential probands were enthusiastic. Although 66% of researchers
      valued proband-initiated contact, only 23% said that probands viewed this
      strategy as important to protecting the privacy of siblings. A substantial
      minority of researchers (37%) said the strategy impeded enrollment, and 44% said
      it was overly burdensome to probands.

PMID- 15855804
TI  - Factor structure of motor signs in essential tremor.
AB  - Motor signs in essential tremor (ET) are varied. Patients may have limb tremors,
      including postural, kinetic (e.g. writing, pouring), and rest tremors, head
      tremor, voice tremor, or chin tremor. Factor analysis allows one to determine
      whether these signs fall into a smaller number of discrete domains. Such an
      analysis has not been performed on a group of ET cases. ET cases (n = 168) were
      recruited from the Neurological Institute of New York and a videotaped
      examination was performed. A factor analysis was performed on 17 motor items.
      Four distinct factors emerged, explaining 68.7% of the total variance. These were
      factor I (action tremor in the dominant arm), factor II (action tremor in the
      nondominant arm), factor III (tremor at rest) and factor IV (chin tremor, head
      tremor, and voice tremor). The demonstration of these four factors will be of
      potential use for pathological and genetic studies as well as interventional
      studies, as will be discussed.

PMID- 15855805
TI  - Inter-rater reliability of delirium rating scales.
AB  - Delirium continues to be under-recognized despite use of rating scales with
      apparently high inter-rater reliability. We analyzed the inter-reliability data
      of published rating scales for delirium using a standard questionnaire to
      evaluate if the inter-rater reliability was assessed rigorously. Most studies
      employed a heterogeneous group of cognitively disordered elderly, however other
      aspects of inter-rater reliability estimation were less than rigorous. This
      suggests that the reported reliability may be spuriously high, which may have
      implications on the ability of clinicians to discriminate delirium from other
      causes of cognitive impairment in practice. The methodology of assessing inter
      rater reliability of delirium scales needs to improve and reliability should be
      evaluated when the settings of administration change substantially.

PMID- 15855806
TI  - Different effect of cyclosporine A and mycophenolate mofetil on passive Heymann
      nephritis in the rat.
AB  - BACKGROUND: While cyclosporine A (CsA) is an effective therapy for nephrotic
      syndrome, it has nephrotoxic side effects. We compared the anti-proteinuric
      effects and nephrotoxicity in rats with passive Heymann nephritis (PHN) of CsA
      and mycophenolate mofetil (MMF). METHODS: PHN was induced in female Wistar rats.
      Two treatment groups consisting of 8 rats each received either 25 mg of CsA or 25
      mg of MMF/kg body weight/day and were compared with untreated controls. Kidney
      function and proteinuria were monitored over 4 weeks. Western blots were used for
      densitometric analysis of renal cyclooxygenase-2 (COX-2) protein expression.
      Thromboxane B2 (TxB2) and 6-keto-PGF(1alpha) were determined by radioimmunoassays
      (RIAs) in renal tissue and urine. RESULTS: Rats with PHN exhibited a marked
      proteinuria of 12.76 +/- 4.42 vs. 0.73 +/- 0.28 mg/24 h (p < 0.01) and showed
      increased glomerular concentrations of TxB2 and 6-keto-PGF(1alpha) (992.6 +/-
      216.9 and 1,187.0 +/- 54.2 pg/mg protein, respectively) compared with healthy
      controls (595 +/- 196.17 and 729 +/- 297.84, respectively) and a strongly induced
      COX-2 protein expression. CsA and MMF treatment reduced PHN-related proteinuria
      to 2.10 +/- 1.47 and 1.47 +/- 7.2 mg/24 h, respectively. In rats with PHN, CsA
      induced a significant deterioration of renal function and enhanced urine
      excretion of thromboxane A2, paralleled by a significant, twofold increase in COX
      2 protein expression and renal prostaglandins. By contrast, MMF treatment in rats
      with PHN was not nephrotoxic and had no effect on prostaglandin production. COX-2
      protein expression under MMF was suppressed. CONCLUSION: While the
      antiproteinuric efficacy of MMF and CsA in PHN was comparable, the absence of
      nephrotoxicity might favor MMF in the treatment of nephrotic syndrome. The CsA
      induced increase in COX-2 expression and COX-2-dependent prostacyclin may
      indicate a mechanism that compensates nephrotoxicity in the diseased and CsA
      exposed kidney.

PMID- 15855807
TI  - TGF-beta1-induced connective tissue growth factor (CCN2) expression in human
      renal proximal tubule epithelial cells requires Ras/MEK/ERK and Smad signalling.
AB  - BACKGROUND: Connective tissue growth factor (CTGF, CCN2) plays a fundamental role
      in the development of tissue fibrosis by stimulating matrix deposition and
      mediating many of the pro-fibrotic effects of transforming growth factor (TGF)
      beta. CCN2 induction by TGF-beta in renal proximal tubule epithelial cells
      (PTECs) is likely to play an important role in the development of
      tubulointerstitial fibrosis. In this study, we investigated the induction of CCN2
      by TGF-beta1 and the possible mechanisms of this induction in human PTECs.
      METHODS: Experiments were performed on primary and transformed (human kidney cell
      (HKC)-clone 8) human PTECs. Induction of CCN2 in response to TGF-beta1 was
      studied at the gene promoter level by reporter gene assay, mRNA by semi
      quantitative RT-PCR and protein by immunoblotting. While chemical inhibitors were
      used to assess the role of Ras/MEK/ERK1,2 signalling, an HKC cell line over
      expressing Smad7 was used to assess the role of Smad signalling in induction of
      CCN2 by TGF-beta1. RESULTS: TGF-beta1 induced CCN2 promoter activity, mRNA and
      protein in human PTECs. TGF-beta1-dependent CCN2 promoter activity was reduced by
      inhibiting Ras and MEK activation. MEK inhibition also resulted in inhibition of
      the TGF-beta1-induced secreted CCN2 protein. There was no significant increase in
      CCN2 gene promoter activity or protein by TGF-beta1 in Smad7 over-expressing
      HKCs. CONCLUSIONS: TGF-beta1 induces the expression of CCN2 in human PTECs. This
      induction is dependent on Ras/MEK/ERK and Smad signalling. Inhibiting TGF-beta
      induced CCN2 by targeting Smad and/or Ras/MEK/ERK1,2 signalling pathways could be
      of therapeutic value in renal fibrosis.

PMID- 15855808
TI  - Increased urinary TGF-beta1 and cortical renal GLUT1 and GLUT2 levels: additive
      effects of hypertension and diabetes.
AB  - BACKGROUND/AIM: Diabetes and mesangial stretch caused by hypertension increase
      mesangial matrix deposition which is induced by local production of transforming
      growth factor beta 1 (TGF-beta1). Both conditions are associated with cortical
      GLUT1 overexpression. We evaluated the effect of genetically determined
      hypertension and its association with diabetes on urinary TGF-beta1 and cortical
      GLUT1 and GLUT2 expression. METHODS: We studied Wistar-Kyoto rats (controls, C)
      and spontaneously hypertensive rats (SHR), weighing approximately 210 g, 30 days
      after the injection of streptozotocin (diabetic, D) or citrate buffer (10 C, 9
      SHR, 12 C-D and 15 SHR-D). Twenty-four-hour urine was collected for glucose,
      albumin, and TGF-beta1 determinations. Catheters were implanted into the femoral
      artery to measure the arterial blood pressure in conscious animals 1 day later.
      Then GLUT1 and GLUT2 protein levels (Western blotting) in renal cortex and
      medulla were evaluated. RESULTS: The cortical GLUT1 levels were 5, 2, and 7 times
      higher in SHR, C-D, and SHR-D groups versus C group (p < 0.05); the GLUT2
      contents were 1.5, 1.8, and 2.3 times higher in SHR, C-D and SHR-D groups versus
      C group (p < 0.05). The urinary TGF-beta1 level was elevated by diabetes and
      diabetes and hypertension, but not by hypertension alone: 1.39 +/- 0.2, 2.34 +/-
      0.6, 18.2 +/- 3.2, and 28.8 +/- 7.6 ng/24 h, respectively, in C, SHR, C-D, and
      SHR-D groups (p < 0.05). CONCLUSIONS: Diabetes, hypertension, and especially
      their association increase the renal cortical GLUT1 and GLUT2 levels. The
      magnitude of GLUT1 overexpression caused by hypertension is higher than that
      induced by diabetes alone. The impact on urinary TGF-beta1 occurs when diabetes
      and hypertension are associated, suggesting an effect that is triggered in the
      presence of GLUT1 overexpression and hyperglycemia.

PMID- 15855809
TI  - Altered Ca2+ homeostasis in human uremic skeletal muscle: possible involvement of
      cADPR in elevation of intracellular resting [Ca2+].
AB  - BACKGROUND: Patients with chronic renal failure may develop muscle weakness and
      fatigability due to disorders of skeletal muscle function, collectively known as
      the uremic myopathy. Cyclic adenosine diphosphate-ribose (cADPR), an endogenous
      metabolite of beta-NAD+, activates Ca2+ release from intracellular stores in
      vertebrate and invertebrate cells. The current study investigated the possible
      role of cADPR in uremic myopathy. METHODS: We have examined the effect of cADPR
      on myoplasmic resting Ca2+ concentration ([Ca2+]i) in skeletal muscle obtained
      from control subjects and uremic patients (UP). [Ca2+]i was measured using double
      barreled Ca2+-selective microelectrodes in muscle fibers, prior to and after
      microinjections of cADPR. RESULTS: Resting [Ca2+]i was elevated in UP fibers
      compared with fibers obtained from control subjects. Removal of extracellular
      Ca2+, or incubation of cells with nifedipine, did not modify [Ca2+]i in UP or
      control fibers. Microinjection of cADPR produced an elevation of [Ca2+]i in both
      groups of cells. This elevation was not mediated by Ca2+ influx, or inhibited by
      heparin or ryanodine. [cADPR]i was determined to be higher in muscle fibers from
      UP compared to those from the control subjects. Incubation of cells with 8-bromo
      cADPR, a cADPR antagonist, partially reduced [Ca2+]i in UP muscle fibers and
      blocked the cADPR-elicited elevation in [Ca2+]i in both groups of muscle cells.
      CONCLUSION: Skeletal muscles of the UP exhibit chronic elevation of [Ca2+]i that
      can be partially reduced by application of 8-bromo-cADPR. cADPR was able to
      mobilize Ca2+ from intracellular stores, by a mechanism that is independent of
      ryanodine or inositol trisphosphate receptors. It can be postulated that an
      alteration in the cADPR-signaling pathway may exist in skeletal muscle of the
      patients suffering from uremic myopathy.

PMID- 15855810
TI  - Optimizing hemoglobin levels and beyond: strength for living and meaningful
      survival?

PMID- 15855811
TI  - Cancer-related anemia: pathogenesis, prevalence and treatment.
AB  - Cancer-related anemia is a cytokine-mediated disorder resulting from complex
      interactions between tumor cells and the immune system. Overexpression of certain
      inflammatory cytokines results in shortened survival of red blood cells,
      suppression of erythroid progenitor cells, impaired iron utilization, and
      inadequate erythropoietin production. Numerous other factors may also contribute
      to the development of anemia in cancer patients. The European Cancer Anaemia
      Survey (ECAS) has provided the most current, comprehensive, prospectively
      collected data on the incidence and prevalence of anemia among cancer patients,
      as well as important perspectives on anemia treatment and relationship of
      hemoglobin and performance status. ECAS enrolled over 15,000 treated and
      untreated patients with various malignancies from cancer centers in 24 European
      countries and followed them for up to 6 months. The initial analysis of the ECAS
      data revealed that 39% of the total cancer patient population was anemic
      (hemoglobin <12.0 g/dl) at enrollment, although the rate varied according to
      tumor type, disease status, and cancer treatment status. Of the patients who were
      not anemic at enrollment and started cancer treatment during the survey, those
      undergoing chemotherapy--either alone or in combination with radiotherapy--had
      the highest incidence of anemia (63 and 42%, respectively). Low hemoglobin levels
      correlated with poor performance status and only 40% of patients who were anemic
      at some time during the survey received treatment for their anemia. These
      findings are noteworthy, since a growing body of clinical evidence indicates that
      the treatment of anemia can significantly improve patients' quality of life and
      may also improve the clinical outcome.

PMID- 15855812
TI  - Cancer-related anemia: biological findings, clinical implications and impact on
      quality of life.
AB  - Anemia is a common symptom in cancer patients. The relationship among anemia,
      cancer progression and clinical outcomes of cancer treatment is complex and much
      remains to be elucidated. One hypothesis for an etiological link is that anemia
      contributes to the development of tumor hypoxia, which in turn has been shown to
      induce proteomic and genomic changes within the tumor cells that ultimately favor
      malignant progression and treatment resistance. A substantial body of clinical
      data indicates that anemia can be a significant independent prognostic factor for
      treatment response and survival in cancer patients treated with chemotherapy or
      radiotherapy. In addition, studies have shown a correlation between anemia and
      decline in quality of life (QOL) in cancer patients. Of the many factors that
      impact cancer patients' QOL, fatigue has emerged as the most prevalent,
      troubling, under-recognized and under-treated of all symptoms experienced by
      anemic cancer patients. Systematic correction of anemia with appropriate
      supportive therapies prior to or during chemotherapy or radiotherapy may enhance
      patients' QOL.

PMID- 15855813
TI  - Standard of care for cancer-related anemia: improving hemoglobin levels and
      quality of life.
AB  - The introduction of recombinant human erythropoietin (rHuEPO) has proven to be a
      major advance in the therapeutic options available for managing anemia in cancer
      patients. The results of placebo-controlled clinical trials and large, community
      based, open-label studies have confirmed that epoetin alfa, a recombinant human
      erythropoietin, significantly reduces transfusion requirements, and reliably
      increases hemoglobin (Hb) levels in anemic (Hb level <12 g/dl) cancer patients
      undergoing chemotherapy. Increased Hb improves patients' energy level and their
      ability to perform the activities of daily living, as well as their overall
      quality of life (QOL). These findings are independent of tumor type and disease
      status and are comparable in patients receiving nonplatinum- and platinum-based
      chemotherapeutic regimens. Furthermore, more than a decade of use in clinical
      trials and by physicians in routine clinical practice has demonstrated that
      epoetin alfa is safe and well tolerated when used to treat cancer patients with
      anemia. The availability of epoetin alfa as an alternative to transfusion has
      changed practices in anemia management; physicians can now treat anemia with the
      goal of achieving adequate Hb levels to relieve anemia-related fatigue, a major
      symptom contributing to decreased QOL in cancer patients. Incremental benefit
      analysis has shown that increasing Hb level from 11 g/dl to 12 g/dl yields the
      greatest improvement in QOL per 1 g/dl increase in Hb. The demonstrated efficacy
      of epoetin alfa for increasing Hb levels and improving patient QOL have made this
      agent a rationale choice for management of cancer-related anemia. Ongoing
      research will continue to provide new insights into best management of anemia
      with epoetin alfa in cancer patients.

PMID- 15855814
TI  - An M-like potassium current in the guinea pig cochlea.
AB  - Potassium M currents play a role in stabilizing the resting membrane potential.
      These currents have previously been identified in several cell types, including
      sensory receptors. Given that maintaining membrane excitability is important for
      mechano-electrical transduction in the inner ear, the presence of M currents was
      investigated in outer hair cells isolated from the guinea pig hearing organ.
      Using a pulse protocol designed to emphasize M currents with the whole-cell patch
      clamp technique, voltage- and time-dependent, non-inactivating, low-threshold
      currents (the hallmarks of M currents) were recorded. These currents were
      significantly reduced by cadmium chloride. Results from RT-PCR analysis indicated
      that genes encoding M channel subunits KCNQ2 and KCNQ3 are expressed in the
      guinea pig cochlea. Our data suggest that guinea pig outer hair cells express an
      M-like potassium current that, following sound stimulation, may play an important
      role in returning the membrane potential to resting level and thus regulating
      outer hair cell synaptic mechanisms.

PMID- 15855815
TI  - Rapid adaptation of pancreatic exocrine function to short-term alcohol feeding in
      rats.
AB  - BACKGROUND: Chronic alcohol consumption increases the risk of pancreatitis in
      humans. Functional hyperstimulation/hypersecretion of the pancreas during chronic
      alcohol consumption appears to precede the onset of pancreatitis, and may
      contribute to the increased susceptibility to pancreatitis in alcoholics.
      However, the origin, nature and timing of hyperstimulation/hypersecretion are
      unknown. METHODS: Male Wistar rats were pair-fed ethanol liquid diet for 15-18
      days (including one 9-day dose ramp-up phase) or regular liquid diets before
      placement of pancreatic, biliary, duodenal and venous catheters. Basal and
      stimulated pancreatic secretions were measured with or without acute alcohol
      infusion. Pancreatic secretion was stimulated with intravenous bethanechol, 2
      deoxy-D-glucose (2-DG), cholecystokinin (CCK), octapeptide (CCK-8), intraduodenal
      meal, or vehicle. RESULTS: Acute alcohol potentiated 2-DG stimulated pancreatic
      secretion (184%, p < 0.05), whereas the response to CCK was unchanged, and the
      response to bethanechol was decreased (78%, p < 0.05). Short-term alcohol
      exposure lessened the exaggerated protein secretory response to 2-DG seen in
      acute alcohol exposure rats and increased the protein response to bethanechol
      (141%, p < 0.05), CCK (187%, p < 0.05) and meal (217%, p < 0.05). CONCLUSION: The
      pancreas is sensitive to acute alcohol ingestion with inhibition of acinar cell
      function. Rapid adaptation occurs with short-term alcohol feeding, resulting in
      an exaggerated response to cholinergic input at the acinar cells, plus
      disinhibition of CCK and meal-stimulated pancreatic secretion. The central
      response to 2-DG and CCK are similar to area postrema lesions. Adaptation appears
      to be in response to alcohol-associated inhibition of the neurohormonal
      stimulatory pathway and compensatory upregulation at the acinar cell level.

PMID- 15855816
TI  - Plasmapheresis in the management of acute severe hyperlipidemic pancreatitis:
      report of 5 cases.
AB  - BACKGROUND/AIM: Hyperlipidemic pancreatitis is an acute and potentially life
      threatening complication of hypertriglyceridemia that can be provoked when
      triglyceride levels (TGL) exceed 11.3 mmol/l (1,000 mg/dl). Except for standard
      symptomatic treatment, plasmapheresis has been performed to rapidly reduce TGL
      and chylomicron levels in the blood. In 5 patients with hyperlipidemic
      pancreatitis, treatment with plasmapheresis was evaluated. METHODS: Five male
      patients who suffered from acute pancreatitis with severe primary hyperlipidemia
      were studied. In addition to the standard treatment, they were treated with
      plasmapheresis. RESULTS: Plasma exchange lowered the lipid level and TGLs in all
      cases. It also improved abdominal pain, the clinical state of the patients, and
      signs and symptoms of the disease. Complications of treatment were not
      encountered, none of the patients died and only 1 patient underwent surgery.
      Follow-up of the patients lasted 4-28 months, and recurrence of pancreatitis was
      not noted. CONCLUSION: Our study showed that plasmapheresis was successfully
      applied in patients with hyperlipidemic pancreatitis, especially to improve the
      acute phase of the disease.

PMID- 15855817
TI  - Expression of Ras GTPase isoforms in normal and diseased pancreas.
AB  - BACKGROUND: Ki-Ras is well studied in its oncogenic form in relation to
      pancreatic pathologies. However, the individual contribution of each of the wild
      type Ras isoforms (Ha-, Ki-, and N-) in pancreatic cells in health and disease is
      unknown. METHODS: Archival formalin-fixed, paraffin-embedded specimens of normal
      (n = 6) and malignant pancreas (n = 35) were used for immuno-histochemical
      detection of Ras isoforms using a modified polymer system. In addition,
      immunogold labelling for Ras isoforms was done for subcellular localisation under
      electron microscopy. RESULTS: Pancreatic ductal cells expressed Ha-Ras in the
      cytoplasm, with Ki-Ras in the apical region and N-Ras (50% of cases) in a
      supranuclear distribution. Pancreatic acinar cells express all three isoforms
      with some nuclear expression of Ki-Ras and supranuclear expression of N-Ras.
      Islets show Ki- and Ha-Ras mainly with differential expression of Ha-Ras (beta
      cells showing less Ha-Ras and more Ki-Ras than alpha cells). Electron microscopy
      shows that Ha-Ras is mainly localised in the endoplasmic reticulum and Golgi
      apparatus of the acinar cells with some plasma membrane localisation of Ki-Ras in
      the ductal cells. There was no change in any of the Ras isoform expression in the
      ductal or acinar cells in various malignancies studied (Mann-Whitney U test, p >
      0.1). CONCLUSIONS: Ras isoforms have distinct and separate cellular and
      subcellular distribution that may persist even in the malignantly transformed
      state. Understanding this distinct functional distribution patterns in detail is
      an essential step if mutant Ki-Ras is to be targeted in the pancreas by genetic
      or molecular therapeutic tools.

PMID- 15855818
TI  - In vitro effects of intravenous anesthetics on the sphincter of Oddi strips of
      sheep.
AB  - BACKGROUND: Intravenous anesthetics are often used for conscious sedation in
      endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincter of
      Oddi (SO) manometry. This study was designed to investigate the direct effects of
      some intravenous anesthetics on SO in sheep. METHODS: In sheep SO rings, changes
      in isometric tension in response to cumulative concentrations of intravenous
      anesthetics were determined, and values for Emax (mean maximal inhibition) and
      pD2 (i.e. the negative logarithm of the concentration for the half-maximal
      response, EC50) were compared. RESULTS: Meperidine (10(-7) to 3 x 10(-5) M),
      fentanyl (10(-7) to 3 x 10(-5) M), midazolam (10(-7) to 3 x 10(-5) M) and
      propofol (10(-7) to 3 x 10(-4) M) induced concentration-dependent relaxations on
      SO precontracted with carbachol (10(-6) M). Emax and pD2 values following
      meperidine, fentanyl and midazolam administration were significantly greater than
      after propofol (p < 0.05). There were no significant differences in Emax and pD2
      values for meperidine, fentanyl and midazolam. CONCLUSION: These results suggest
      that meperidine, fentanyl and midazolam are equipotent relaxants in the sheep SO
      in vitro. The relaxatory effect of propofol was 10 times less potent compared to
      the above agents, and it can be beneficial during SO manometry in controlled
      clinical human studies.

PMID- 15855819
TI  - Defective DNA mismatch repair in long-term (> or =3 years) survivors with
      pancreatic cancer.
AB  - BACKGROUND/AIMS: Defective DNA mismatch repair (MMR) in pancreatic cancer,
      reported in up to 13% of sporadic pancreatic cancers, may predict a good
      prognosis. To determine if long-term survival in pancreatic cancer could be
      attributed to defective DNA MMR, we ascertained its prevalence in 35 pancreatic
      cancer patients who survived > or =3 years after surgery. METHODS: We performed
      immunohistochemistry (IHC) for MMR proteins hMLH1, hMSH2, and hMSH6 in all 35
      tumors and microsatellite instability (MSI) studies in 34/35 tumors using 10
      microsatellite markers in paired normal and tumor DNA. Defective DNA MMR was
      defined as absence of protein expression on IHC and/or MSI in > or =30% of
      markers studied. RESULTS: On IHC, 3/35 (8.6%) tumors had defective DNA MMR. All 3
      had absent expression of a DNA MMR protein (hMLH1 in 2 and hMSH2) and 2/3 also
      had MSI; the third could not be tested. Definitely 2, and probably all 3 patients
      had hereditary nonpolyposis colon cancer as determined by clinical and genetic
      profiles. CONCLUSION: Defective DNA MMR is uncommon in long-term survivors of
      pancreatic cancer and does not account for the survival benefit in those with
      sporadic pancreatic cancer.

PMID- 15855820
TI  - Beta-cell function and insulin resistance evaluated by HOMA in pancreatic cancer
      subjects with varying degrees of glucose intolerance.
AB  - BACKGROUND/AIMS: To gain insights into pathogenesis of pancreatic cancer
      associated diabetes. METHODS: Using homeostasis model assessment (HOMA), we
      estimated beta-cell function (BCF) and insulin resistance (IR) from fasting
      plasma glucose (FPG) and insulin in 67 normoglycemic controls and 62 age- and BMI
      matched normoglycemic pancreatic cancer patients. In addition, we studied 73
      pancreatic cancer subjects with glucose intolerance; 21 had impaired FPG and 51
      had diabetes. RESULTS: BCF was similar in controls and normoglycemic pancreatic
      cancer subjects (64 +/- 5 vs. 78 +/- 9, p = ns), while IR was higher in
      pancreatic cancer subjects with normal FPG (1.6 +/- 0.6 vs. 1.1 +/- 0.1, p =
      0.002). Among pancreatic cancer subjects, those with impaired FPG had markedly
      decreased BCF compared to those with normal FPG (44 +/- 5 vs. 78 +/- 9, p < 0.02)
      without significant difference in IR (1.9 +/- 0.2 vs. 1.6 +/- 0.6, p = ns). In
      cancer subjects, those with diabetes had markedly increased IR compared to those
      with impaired FPG (3.2 +/- 0.3 vs. 1.9 +/- 0.2, p < 0.0001), while the BCF was
      similar (37 +/- 4 vs. 44 +/- 5). CONCLUSION: Diabetes associated with pancreatic
      cancer is likely due to a combination of marked decline in BCF and increased
      insulin resistance.

PMID- 15855821
TI  - Treating patients with autoimmune pancreatitis: results from a long-term follow
      up study.
AB  - BACKGROUND: Steroid therapy is currently common treatment for autoimmune
      pancreatitis (AIP); however, indications of steroid therapy have yet to be
      established, and the clinical course after steroid therapy is unknown. METHODS: A
      total of 23 patients with AIP were subdivided into 4 groups according to the
      initial treatments undertaken. They were treated with pancreatoduodenectomy on
      suspicion of pancreatic tumor in 6 patients, choledochoduodenostomy with
      pancreatic biopsy in 4 patients, supportive therapy in 3 patients, and steroid
      therapy in 10 patients. Clinical course of AIP in each group was examined.
      RESULTS: Prognosis of the AIP patients is almost good except for the 2 patients
      who progressed to pancreatic insufficiency after resection. Two patients without
      jaundice improved spontaneously. Steroid therapy was effective in all patients
      treated, but pancreatic atrophy developed in 5 of these patients. Steroid therapy
      improved insulin secretion and glycemic control in 4 of 7 diabetes mellitus (DM)
      patients. CONCLUSION: To avoid futile surgery, in relatively elderly male
      patients with obstructive jaundice suggestive of pancreatic carcinoma,
      preoperative clinical suspicion of AIP is mandatory. Indications of steroid
      therapy for AIP are thought to be obstructive jaundice due to stenosis of the
      bile duct, other associated systemic autoimmune, and DM coincidental with AIP.

PMID- 15855822
TI  - Pancreatic proteases in serum induce leukocyte-endothelial adhesion and
      pancreatic microcirculatory failure.
AB  - BACKGROUND: Neutrophil-mediated tissue injury in acute pancreatitis includes a
      severe reduction of the functional microcirculation via interaction of adhesion
      molecules on leukocytes (MAC-1) and endothelium (ICAM-1). The hypothesis of the
      study was that trypsin and elastase in serum alone lead to the expression of
      these complementary adhesion molecules and result in increased leukocyte
      endothelial interaction (LEI). In addition we evaluated the preventative benefit
      of protease inhibition on these mechanisms. MATERIALS AND METHODS: In vitro:
      Cultured endothelial cells (HUVEC) and human leukocytes (PMN) were stimulated
      with increasing doses of trypsin and elastase. In addition, pre-treatment of PMN
      or HUVEC was performed with protease inhibitors (Nafamostat mesilate, FUT and
      gabexate mesilate, FOY). The expression of ICAM-1 or MAC-1 was evaluated by flow
      cytometry. In vivo: Severe pancreatitis was induced in rats. Microcirculatory
      disturbances were evaluated by real-time confocal microscopy at 9 h in controls
      and acute pancreatitis with or without anti-protease treatment. Additionally, the
      effect of continuous trypsin and elastase infusion on pancreatic microcirculation
      and LEI were evaluated by intravital fluorescence videomicroscopy. RESULTS: Up
      regulation of MAC-1 and ICAM-1 expression requires the presence of serum. The
      maximal increase of MAC-1 and ICAM-1 expression was found at concentrations of
      trypsin or elastase characteristic for acute pancreatitis. FUT or FOY
      significantly reduced protease-induced expression of MAC-1 and ICAM-1. Real-time
      in-vivo microscopy revealed that functional capillary density in acute
      pancreatitis was significantly reduced (267.1 +/- 2.95/mm2 vs. 91.29 +/-
      12.81/mm2) and treatment with FUT significantly reduced this effect (134.6 +/-
      4.6/mm2; p < 0.05 vs. untreated pancreatitis). Infusion of trypsin or elastase
      alone increased LEI in vivo and reduced pancreatic perfusion. CONCLUSION: Both
      trypsin and elastase up-regulate the expression of adhesion molecules on
      leukocytes and endothelial cells in the presence of serum. Increased LEI and
      reduced perfusion of the pancreas, characteristic of acute pancreatitis, is
      induced in vivo by infusion of pancreatic proteases and this effect is partially
      abrogated by their inhibitors. These results support the role of circulating
      trypsin and elastase in promoting pancreatic microcirculatory failure in
      experimental acute pancreatitis.

PMID- 15855823
TI  - Inhibition of different intracellular signal cascades in human pancreatic cancer
      cells.
AB  - BACKGROUND/AIM: Pancreatic cancer is still a malignant disease with a poor
      prognosis. Except for surgery, no curative treatment has been found, albeit large
      research efforts. Agents, such as growth factors and hormones, have been shown to
      stimulate cell proliferation, whereas their receptor antagonists have been less
      efficient to inhibit cell proliferation. The aim of this study was to examine the
      effect of inhibitors of the intracellular signal cascades on pancreatic cancer
      cell number. MATERIALS AND METHODS: A cell line was developed from a patient with
      pancreatic cancer and subcloned to three generations. The four cell lines were
      grown in serum-free medium. The effects of PD98059, LY294002, rapamycin and its
      analogue CCI-779 were tested in dose-response experiments. The chemotherapeutic
      agent gemcitabine, with or without combination of the other potential inhibitor
      drugs in different concentrations, was also examined. The cell number was
      evaluated with the XTT method. RESULTS: PD98059 reduced the cell number in all
      the cell lines tested. At a concentration of 10(-4) M the cell number was reduced
      by 50-90%. LY294002 reduced the cell number by 40-50% at the same concentration.
      Two of four cell lines had their cell number reduced by CCI-779 by 60%, whereas
      the other two cell lines were reduced by 30%. Rapamycin or gemcitabine alone had
      no or only moderate effect on single cell lines. Different combinations of CCI
      779 and gemcitabine led to reduction of the cell number by about 50% in
      concentrations up to 10(-7) M. CONCLUSION: Inhibitors of the intracellular signal
      cascades can reduce the cell number of human pancreatic cancer cell lines.
      Inhibitors of the mitogen-activated protein kinase downstream signalling cascades
      seem to be more efficient than the other inhibitors. PD98059 and CCI-779, in
      combination with gemcitabine, could be worth studying in clinical conditions.

PMID- 15855824
TI  - Overexpression of Polo-like kinase 1 is a common and early event in pancreatic
      cancer.
AB  - BACKGROUND: There is abundant evidence from in vivo and in vitro studies that
      Polo-like kinase 1 (PLK1) plays a crucial role in the regulation of proliferative
      activity of normal and malignant cells. Therefore, PLK1 has been proposed as a
      new target for antineoplastic treatment strategies. METHODS: We conducted an
      immunohistochemical expression study for PLK1 on 86 cases of pancreatic
      adenocarcinoma as well as on 5 cases of chronic pancreatitis. Additionally, we
      investigated the correlation of PLK1 expression levels with clinicopathological
      data and patient survival. RESULTS: PLK1 was found overexpressed in pancreatic
      neoplasia as early as in pancreatic intraepithelial neoplasia III lesions,
      whereas benign acinar pancreatic parenchyma and ductal epithelia showed only
      focal PLK1 positivity. Invasive pancreatic adenocarcinomas were PLK1 positive in
      47.7% of cases. No correlation of PLK1 positivity and the extent of tumour spread
      was evident, nor did PLK1 expression correlate with tumour grade or patient
      prognosis. Prognostic factors in our study cohort were nodal status and tumour
      grade. CONCLUSIONS: The fact that half of the invasive pancreatic carcinomas
      strongly overexpressed PLK1 indicates that inhibition of this mitotic key
      regulator might represent a rewarding approach in the treatment of early and late
      pancreatic carcinoma.

PMID- 15855825
TI  - Detection of recurrent pancreatic cancer: comparison of FDG-PET with CT/MRI.
AB  - OBJECTIVE: To determine the value of fluorine-18-fluoro-2-deoxy-D-glucose
      positron emission tomography (FDG-PET) for the detection of recurrent pancreatic
      cancer in comparison to computed tomography (CT) and magnetic resonance imaging
      (MRI). METHODS: Thirty-one patients with suspected recurrence after surgery were
      included. Inclusion criteria were sudden weight loss, pain or increased CA 19-9
      levels. FDG-PET was performed in all patients. After visual analysis, maximal
      standardized uptake values (SUVmax) were determined by placing regions of
      interest on the pancreas bed. Additionally, all patients underwent contrast
      enhanced multidetector CT (n = 14) or MR (n = 17) imaging. Positive findings at
      FDG-PET or CT/MRI were compared to follow-up. RESULTS: All patients relapsed. Of
      25 patients with local recurrences upon follow-up, initial imaging suggested
      relapse in 23 patients. Of these, FDG-PET detected 96% (22/23) and CT/MRI 39%
      (9/23). Local SUVmax ranged from 2.26 to 16.9 (mean, 6.06). Among 12 liver
      metastases, FDG-PET detected 42% (5/12). CT/MRI detected 92% (11/12) correctly.
      Moreover, 7/9 abdominal lesions were malignant upon follow-up of which FDG-PET
      detected 7/7 and CT/MR detected none. Additionally, FDG-PET detected extra
      abdominal metastases in 2 patients. CONCLUSION: In patients suspected of
      pancreatic cancer relapse; FDG-PET reliably detected local recurrences, whereas
      CT/MRI was more sensitive for the detection of hepatic metastases. Furthermore,
      FDG-PET proved to be advantageous for the detection of nonlocoregional and extra
      abdominal recurrences.

PMID- 15855826
TI  - Genetic and biochemical characterization of the E32del polymorphism in human
      mesotrypsinogen.
AB  - BACKGROUND/AIMS: Mesotrypsin is a minor pancreatic digestive enzyme that degrades
      dietary trypsin inhibitors in the gut. In this study, we tested the hypothesis
      that the E32del genetic variant of mesotrypsin might represent a risk factor for
      the development of chronic pancreatitis, as a result of enhanced degradation of
      pancreatic secretory trypsin inhibitor. METHODS: We screened 97 German patients
      with chronic pancreatitis of alcoholic etiology and 109 healthy controls for the
      presence of the E32del variant and characterized the biochemical properties of
      E32del mesotrypsinogen. RESULTS: Higher allele frequency of the E32del variant
      was detected in the control population (25.7 vs. 18.0%), but the difference was
      not significant (p = 0.062). Recombinant E32del mesotrypsin exhibited normal
      catalytic activity, characteristic inhibitor resistance and inability to activate
      pancreatic zymogens. Degradation of trypsin inhibitors was unaffected by the
      E32del genotype. Interestingly, mesotrypsinogen-E32del was biochemically
      distinguishable from mesotrypsinogen by its faster activation with bovine
      enterokinase, while activation by human enterokinase, trypsin or cathepsin B was
      unchanged. CONCLUSION: The results classify E32del mesotrypsinogen as a frequent
      polymorphic variant, which is not associated with chronic alcoholic pancreatitis.

PMID- 15855827
TI  - Total dorsal pancreatectomy for intraductal papillary mucinous neoplasm in a
      patient with pancreas divisum.
AB  - We report a case of intraductal papillary mucinous neoplasm confined to the
      dorsal (Santorini) pancreatic duct. A 51-year-old woman presented with a cystic
      lesion in the head of her pancreas and pancreas divisum. A biopsy taken during
      cyst-enteric drainage revealed dysplastic epithelium so the patient was scheduled
      for resection. At operation, excision of the entire dorsal pancreas was performed
      with preservation of the unaffected ventral pancreas and the spleen and its
      vessels. Over 6 years later she remains well with stable weight and a good
      quality of life. This case illustrates the benefits of anatomical preservation in
      pancreatic resection, and was performed some years prior to the only other
      reported similar case.

PMID- 15855828
TI  - Successful treatment of solid-pseudopapillary tumor of the pancreas with multiple
      liver metastases.
AB  - The solid-pseudopapillary tumor (SPT) is a very rare pancreatic neoplasm that
      predominantly affects young females. About 450 cases have been described in the
      world literature and approximately 20% of the reported patients were children.
      The occurrence of SPT with distant metastases in children is extremely rare with
      only two previously reported cases. We now report a 16-year-old Asian girl with a
      large SPT and synchronous multiple liver metastases who was successfully treated
      in a 2-step strategy, including initial pylorus-preserving partial
      duodenopancreatectomy, right hemicolectomy, resection and allografting of the
      portal vein and secondary resection of 12 liver metastases. The patient is
      disease free after a follow-up of 18 months after resection of the primary tumor,
      suggesting that an aggressive surgical treatment might also be justified for
      metastasized SPT.

PMID- 15855829
TI  - Spontaneous regression of a pancreatic head mass and biliary obstruction due to
      autoimmune pancreatitis.
AB  - BACKGROUND: Autoimmune pancreatitis is an evolving entity. METHODS: A patient who
      had spontaneous regression of a pancreatic head mass and biliary obstruction due
      to autoimmune pancreatitis is presented. RESULTS: A 58-year-old diabetic woman
      with jaundice was referred for pancreatic head carcinoma diagnosed by magnetic
      resonance imaging (MRI). At laparotomy, a pancreatic head mass (4 x 3 cm) that
      involved the transverse mesocolon and two other hard masses (1 cm) in the
      pancreatic body and tail were found. The gallbladder was palpated as a hard tumor
      mass. Frozen section examination of the gallbladder and pancreatic biopsies
      revealed cholecystitis and pancreatitis with lymphoplasmacytic infiltration. The
      common bile duct was brittle and unsuitable for anastomosis. Starting 1 month
      after the operation, drainage from the biliary catheter decreased gradually and
      stopped. There was no parenchymal lesion on MRI examination in the 2nd
      postoperative month. Cholangiography from the percutaneous catheter showed flow
      of contrast agent into the duodenum. Serum immunoglobulin G, G4 and E levels were
      increased. CONCLUSION: To the best of our knowledge, this is the first report of
      spontaneous regression of a pancreatic head mass and biliary obstruction due to
      autoimmune pancreatitis.

PMID- 15855830
TI  - Voltage-dependent and frequency-independent inhibition of recombinant Cav3.2 T
      type Ca2+ channel by bepridil.
AB  - Effects of bepridil on the low voltage-activated T-type Ca2+ channel (CaV3.2)
      current stably expressed in human embryonic kidney (HEK)-293 cells were examined
      using patch-clamp techniques. Bepridil potently inhibited ICa,T with a markedly
      voltage-dependent manner; the IC50 of bepridil was 0.4 micromol/l at the holding
      potential of -70 mV, which was 26 times as potent as that at -100 mV (10.6
      micromol/l). Steady-state inactivation curve (8.4 +/- 1.7 mV) and conductance
      curve (5.9 +/- 1.9 mV) were shifted to the hyperpolarized potential by 10
      micromol/l bepridil. Bepridil exerted the tonic blocking action but not the use
      dependent block. Bepridil had no effect on the recovery from inactivation of T
      type Ca2+ channels. Thus, high efficacy of bepridil for terminating atrial
      fibrillation and atrial flutter may be considered to be attributed, at least in a
      part, to the T-type Ca2+ channel-blocking actions.

PMID- 15855831
TI  - Plaunotol prevents the progression of acute gastric mucosal lesions induced by
      compound 48/80, a mast cell degranulator, in rats.
AB  - We examined the preventive effect of plaunotol, an antiulcer drug, on acute
      gastric mucosal lesion progression in rats treated once with compound 48/80
      (C48/80). Rats treated with C48/80 (0.75 mg/kg BW, i.p.) received plaunotol (10,
      25 or 50 mg/kg BW, p.o.) 0.5 h after the treatment at which time gastric mucosal
      lesions appeared. The gastric mucosa of C48/80-treated rats showed progressed
      lesions and had increased myeloperoxidase (an index of neutrophil infiltration)
      activity and thiobarbituric acid reactive substances (an index of lipid
      peroxidation) content and decreased ascorbic acid and adherent mucus contents and
      Se-glutathione peroxidase activity at 3 h after C48/80 treatment.
      Postadministered plaunotol attenuated all these changes dose-dependently. These
      attenuating effects of plaunotol were not counteracted by pretreatment with
      indomethacin (5 mg/kg BW, i.p.), a prostaglandin synthesis inhibitor. These
      results indicate that plaunotol prevents the progression of C48/80-induced acute
      gastric mucosal lesions in rats possibly by its anti-inflammatory and antioxidant
      actions, but not by affecting gastric mucosal prostaglandin levels.

PMID- 15855832
TI  - Psychopathology in first-episode schizophrenia and antibodies to Toxoplasma
      gondii.
AB  - OBJECTIVE: Environmental factors such as infectious agents may contribute to the
      psychopathology and aetiology of schizophrenia. Toxoplasma gondii (TG) is a
      candidate infectious agent as it is known to replicate within the human central
      nervous system and to alter behaviour in experimental animals. METHOD: The
      relationship between antibodies to TG and psychopathological symptoms was
      examined in 34 first-episode patients with schizophrenia. RESULTS: Results of
      regression analyses revealed that symptoms on admission, predictors of outcome,
      age and family history of psychiatric disease influenced the levels of antibodies
      to TG. CONCLUSIONS: These results indicate that TG infections may play a role in
      the clinical manifestation of psychopathology in a subgroup of patients with
      schizophrenia.

PMID- 15855833
TI  - A three-axes approach of subtyping the alcohol dependence syndrome.
AB  - Subtyping of alcoholics according to specific characteristics has a long
      tradition in alcoholism research with a number of different typologies that
      emerged in the literature. The goal of the present study was to test a
      multidimensional approach of subtyping with characteristics from different axes.
      Therefore, male inpatients meeting ICD-10 criteria for alcohol dependence were
      rated on three axes by assessing their degree of sensation seeking (personality
      axis), age of alcoholism onset (clinical axis) and level of dopamine activity
      (neurobiological axis). By using a configuration frequency analysis, we
      identified a subtype that was characterized by high sensation seeking early age
      of alcoholism onset and high dopamine activity. This subtype, which is in
      accordance with clinical experience and cannot be explained by antisocial
      personality disorder, embodied a significantly greater proportion of alcoholics
      than expected. The result emphasizes the usefulness of multidimensional
      approaches integrating personality, clinical and neurobiological characteristics.

PMID- 15855834
TI  - Dangerousness and management of delusional misidentification syndrome.
AB  - Many theories have been proposed to help understand delusional misidentification
      syndromes (DMS) and the danger associated with them. We report on three cases
      with histories of paranoid schizophrenia who developed DMS. Two of them acted out
      on delusional thinking toward their sons. Case 1 managed to kill her son and Case
      2 was caught twice trying to choke him. Our case reports suggest that the degree
      of threat perceived by the patient from the delusionally misidentified object is
      the most important factor in determining the patient's response to the delusions.
      Alcohol and substance intoxication facilitated the patients' acting out on their
      delusions, but did not explain the genesis of the delusions. There is a need to
      continue to study patients with DMS in order to provide opportunity for greater
      understanding of the psychopathology of DMS.

PMID- 15855835
TI  - Delusional parasitosis associated with pemoline.

PMID- 15855837
TI  - Trends in I.V. therapy.

PMID- 15855836
TI  - On the road to successful I.V. starts.

PMID- 15855854
TI  - PCNA News.

PMID- 15855856
TI  - AHA scientific statement: practice standards for electrocardiographic monitoring
      in hospital settings: an American Heart Association Scientific Statement from the
      Councils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular
      Disease in the Young: endorsed by the International Society of Computerized
      electrocardiology and the American Association of Critical-Care Nurses.
AB  - The goals of electrocardiographic (ECG) monitoring in hospital settings have
      expanded from simple heart rate and basic rhythm determination to the diagnosis
      of complex arrhythmias, myocardial ischemia, and prolonged QT interval. Whereas
      Computerized arrhythmia analysis is automatic in cardiac monitoring systems,
      computerized ST-segment ischemia analysis is available only in newer-generation
      monitors, and computerized QT-interval monitoring is currently unavailable. Even
      in hospitals with ST-monitoring capability, ischemia monitoring is vastly
      underutilized by healthcare professionals. Moreover, because no computerized
      analysis is available for QT monitoring, healthcare professionals must determine
      when it is appropriate to manually measure QT intervals (eg, when a patient is
      started on a potentially proarrhythmic drug). The purpose of the present review
      is to provide "best practices" for hospital ECG monitoring. Randomized clinical
      trials in this area are almost nonexistent; therefore, expert opinions are based
      upon clinical experience and related research in the field of
      electrocardiography. This consensus document encompasses all areas of hospital
      cardiac monitoring in both children and adults. The emphasis is on information
      clinicians need to know to monitor patients safely and effectively.
      Recommendations are made with regard to indications, time frames, and strategies
      to improve the diagnostic accuracy of cardiac arrhythmia, ischemia, and QT
      interval monitoring. Currently available ECG lead systems are described, and
      recommendations related to staffing, training, and methods to improve quality are
      provided.

PMID- 15855858
TI  - An overview of pulmonary arterial hypertension: risks, pathogenesis, clinical
      manifestations, and management.
AB  - This article focuses on pulmonary arterial hypertension, including both primary
      pulmonary hypertension (PPH) and those forms of pulmonary arterial hypertension
      that are related to other factors, including collagen vascular diseases,
      congenital shunts, portal hypertension, human immunodeficiency viral infection,
      and exposure to specific drugs and toxins. Risks for different types of pulmonary
      arterial hypertension are identified. The common pathogenesis for pulmonary
      arterial hypertension is discussed, and includes an overview of the role of key
      vasoactive substances such as nitric oxide, prostacyclin, endothelin, and
      thromboxane. Typical presenting clinical manifestations, recommendations for
      screening of patients at risk, and key diagnostic findings are discussed. The
      mainstay of treatment is identified as pharmacologic, and may include diuretics,
      digoxin, warfarin, calcium channel antagonists, and prostacyclin analogues such
      as epoprostenol. Surgical interventions are considered as a last resort, and may
      include unilateral or bilateral lung transplant or atrial septostomy. Treatment
      options for patients with pulmonary arterial hypertension hold more hope today
      than they did a decade ago and are identified so as to guide the advanced
      practice nurse in recognizing and then facilitating the appropriate management of
      patients with this rare but disabling disease.

PMID- 15855860
TI  - Secondary pulmonary hypertension: a review of the cardiac causes.
AB  - Pulmonary hypertension (PAH) is defined as mean pulmonary artery pressure greater
      than 25 mm Hg at rest, or greater than 30 mm Hg with exercise. While there are a
      myriad of etiologies for PAH, many times a cardiac etiology may be present. This
      is particularly important from both diagnostic and therapeutic standpoints, as
      many lesions are readily repairable with corrective surgery. Often, PAH may be
      drastically reduced, or even returned to baseline, after surgical correction.
      This article focuses on these cardiac etiologies of secondary PAH. Primary PAH,
      and PAH secondary to disease of the lung parenchyma, will not be discussed.
      Pulmonary hypertension is generated by increased flow through the pulmonary
      arteries, increased resistance to flow, or venous obstruction at the entrance to
      the left atrium. There is no upper limit of PAH that definitively precludes
      surgery, thus all patients with surgically approachable lesions should be
      referred for evaluation.

PMID- 15855861
TI  - Lung transplantation for primary pulmonary hypertension and Eisenmenger's
      syndrome.

PMID- 15855862
TI  - Management of atrial fibrillation in patients with chronic obstructive pulmonary
      disease.
AB  - Atrial fibrillation is the cardiac arrhythmia encountered most often in clinical
      practice. It is triggered by many conditions such as thyroid dysfunction, cardiac
      disease, alcohol, and pulmonary disease. Patients with chronic obstructive
      pulmonary disease (COPD) are susceptible to many insults that can lead to an
      acute deterioration superimposed on chronic disease. Changes in blood gases,
      abnormalities in pulmonary functions, and hemodynamic changes resulting from
      pulmonary hypertension can lead to the development of atrial fibrillation. Atrial
      fibrillation and COPD frequently coexist and complicate treatment of both
      conditions. The treatment of COPD exacerbation may include beta-adrenergic
      agonist and theophylline, which can precipitate atrial fibrillation with rapid
      ventricular response. Pharmacologic and electrical cardioversion may be
      ineffective in the management of atrial fibrillation in patients with COPD until
      respiratory decompensation has been corrected. This article focuses on the
      management of atrial fibrillation in patients with COPD.

PMID- 15855863
TI  - Providing quality end-of-life care.
AB  - End-of-life care involves not only the care of patients but also the care of
      those providing care for patients. The routine demands of providing care for
      patients in end-of-life situations often prevent nurses from working through the
      grief associated with the death of a patient, resulting in frustration,
      depression, stress, and eventually, burnout. It is important to recognize that
      grief and mourning are necessary steps in adjusting to the loss associated with
      the death of a patient or a loved one. The process of mourning can be likened to
      the process of healing, with predictable stages or tasks. As nurses providing
      quality end-of-life care, we can provide an opportunity for a patient's family to
      begin the process of grieving through appropriate interventions while the patient
      is still in the hospital or care facility. Recognizing and respecting the
      appropriateness of individual differences in grief responses creates a means of
      support for both patients and professionals in healthcare settings. By
      understanding grief as a predictable, yet individual, response to the loss of a
      patient or a loved one, we, as nurses, can take care of ourselves while providing
      quality end-of-life care for our patients.

PMID- 15855864
TI  - The 40-year public health battle against cigarette smoking: are we winning?

PMID- 15855865
TI  - [The 60th Annual Scientific Congress--symposium-proposals and related issues on
      advancement in academic activities of our society].

PMID- 15855866
TI  - [A key to head & neck MRI imaging].

PMID- 15855867
TI  - [Evidence-based imaging technology in emergency medicine].

PMID- 15855868
TI  - [Fundamental theory of digital medical informatics: sampling and quantization].

PMID- 15855869
TI  - [Simple measuring instrument using quality assurance and quality control for X
      ray equipment].

PMID- 15855870
TI  - [Management of patient dose in pediatric computed tomography].

PMID- 15855871
TI  - [Safe-keeping of accompanying documents for medical devices].

PMID- 15855872
TI  - [Study of automated segmentation of the cerebellum and brainstem on brain MR
      images].
AB  - MR imaging is an important method for diagnosing abnormalities of the brain. This
      paper presents an automated method to segment the cerebellum and brainstem for
      brain MR images. MR images were obtained from 10 normal subjects (male 4, female
      6; 22-75 years old, average 31.0 years) and 15 patients with brain atrophy (male
      3, female 12; 62-85 years of age, average 76.0 years). The automated method
      consisted of the following four steps: (1) segmentation of the brain on original
      images, (2) detection of an upper plane of the cerebellum using the Hough
      transform, (3) correction of the plane using three-dimensional (3D) information,
      and (4) segmentation of the cerebellum and brainstem using the plane. The results
      indicated that the regions obtained by the automated method were visually similar
      to those obtained by a manual method. The average rates of coincidence between
      the automated method and manual method were 83.0+/-9.0% in normal subjects and
      86.4+/-3.6% in patients.

PMID- 15855873
TI  - [Improving coronary artery imaging quality in the high heart rate region and on
      MDCT using a pulsating cardiac phantom].
AB  - The multi-sector reconstruction (MSR) algorithm and cardiac half-reconstruction
      (CHR) algorithm are the main algorithms used in cardiac reconstruction. Analysis
      of effective temporal resolution (TR) confirmed that optimal rotation speed
      depends on different heart rates when using MSR. During visualization (3D/MPR
      image) and quantitative (EF: ejection fraction) evaluations, it was found that
      image quality and measurement accuracy are well correlated with effective
      temporal resolution (TR) by the different algorithms. The CHR algorithm resulted
      in less desirable image quality at TR 250 ms than that from MSR at high heart
      rates (>75 bpm) in the phantom experiment. We determined that the combination of
      the MSR algorithm and the optimal selection of gantry rotation speed is important
      for obtaining high-quality cardiac imaging in the high heart rate region.

PMID- 15855874
TI  - [Simple method of setting proper exposure in X-ray CT examination of head and
      abdomen].
AB  - In abdominal X-ray computerized tomography (CT) , exposure conditions can be
      established by real-time exposure control and manual procedures, depending on the
      body type. In the former, appropriate dose control can be attained. In the
      latter, dose cannot be controlled to a very precise level, since the dose is
      controlled manually, according to body type. In head X-ray CT, the conditions are
      in most cases established manually. We determined the causal relationship between
      the body mass index (BMI) showing the body type of a subject and the abdominal
      cross section/circumferential length of the subject. Then a water phantom that
      simulated the abdominal area was used to take pictures, with the current time
      integrator changed, relating the section area and circumferential length of the
      water phantom with the body mass index, thereby determining the relationship with
      the current time integrator. Further, a water phantom simulating the head was
      used to take pictures, with the current time integrator changed, thereby
      determining the relationship between the circumferential length of the water
      phantom with the current time integrator. We determined that pictures can be
      taken at a dose that is close to an appropriate dose, when these relationships
      are plotted to determine the standard deviation (SD) for establishing exposure
      conditions.

PMID- 15855875
TI  - [Development of a system to assist patient positioning in radiation therapy].
AB  - We have developed a system to assist in patient positioning for radiation therapy
      that includes an automated registration process between the reference image and
      target volume data before irradiation. The system uses the cross-correlation
      function between images for the automatic positioning processing algorithm.
      Evaluation of the system showed good results in providing highly accurate
      registration. Therefore, the system is suitable for use in clinical study. In
      addition, evaluation of clinical data of the prostate using the system revealed
      displacement of the internal organs.

PMID- 15855876
TI  - [Examination of normal database in three-dimensional SSP].
AB  - The results of statistical image analyses, such as three-dimensional stereotactic
      surface projection (3D-SSP), are affected by the normal database (NDB) used. As a
      general rule, each institution must establish its own NDB for analysis. However,
      the numbers of institutions with the ability to establish their own NDB are
      limited. Therefore, it would be ideal if an NDB suitable for other institutions
      could be established from standard volunteer data gathered at a single
      institution. In this study, we examined the validity of establishing an NDB
      suitable for other institutions from the standard volunteer data gathered at our
      institution, using E.CAM (used as a reference) and IRIX. We established three
      NDBs. One was established from E.CAM, and the other two were from IRIX (in which
      overall FWHM was the same as that of E.CAM with Butterworth filter cutoff
      frequency and using an identical algorithm for image-reconstruction of E.CAM). We
      then compared the mean values and standard deviations of the NDBs, and also
      examined the effects on the Z-score map. We determined that the NDB that had been
      established was suitable for other institutions, using identical FWHM (resolution
      of SPECT imaging) and an algorithm for image-reconstruction.

PMID- 15855877
TI  - Association of G-protein beta-3 subunit gene (GNB3) T825 allele with Type II
      diabetes.
AB  - To date, the human G-protein beta 3 subunit (GNB3) gene and some of its variants
      represent some of the best examples of genetic influences that are involved in
      the determination of hypertension and obesity, which make it a sensible candidate
      gene for type 2 diabetes. To assess the influence of GNB3 in type II diabetes
      mellitus (NIDDM), we carried out a retrospective, case-control study of variant
      GNB3 825C>T for putative correlations with NIDDM amongst nationals from the
      United Arab Emirates (Emirati) - an ethnic group characterized by no alcohol
      intake and no cigarette smoking. We investigated a sample population of 510
      Emirati (257 men, 253 women) comprising two groups - 254 controls and 256
      patients with clinical diagnoses of type 2 diabetes (cases). The GNB3 C825T
      dimorphism showed an association with NIDDM Chi2 =22.5, 2 df, P<0.001). Further
      analysis revealed that the GNB3 T/T 825 genotype was positively associated with
      NIDDM (Yates corrected Chi2=20.6, 2 df, P<0.001; odds ratio of 2.44 with a 95%
      confidence interval of 1.64 - 3.63) compared to pooled CC/CT genotypes. Our data
      shows that GNB3 T825 allele may be involved in the pathogenesis of DM through a
      pathway that is different from the one implicated in obesity.

PMID- 15855879
TI  - Problems and possibilities in the differential diagnosis of Syndrome
      Spinocerebellar Ataxia.
AB  - Differential diagnosis in neurologic patients with spinocerebellar syndrome is
      complex as a result of the great degree of variability in phenotypic and genetic
      aspects of more than 200 nosological entities. In the past decade, genetic
      etiology has been discovered in part of the diseases and the term
      ''spinocerebellar ataxia'' has become, from a neurologic point of view, a loose
      definition applied to a group of autosomal dominant diseases. Topical extensive
      literature about differential diagnoses of ataxias usually refers to genetics
      classification or is produced by a group of radiologists, elektrophysiologists
      and biologists as well as others in the field. A further problem is that the
      majority of studies do not take into account other acquired illnesses and
      diseases which may fundamentally alter the symptomology and course of a primary
      disease, not to mention the possibility of concomitancy in hereditary diseases.
      The following article was prompted by daily contact with ataxic patients and
      related issues raised by colleagues; its goal is to clarify problems faced by
      child neurologists and neurologists in clinical practice.

PMID- 15855878
TI  - The American lobster, Homarus americanus, contains morphine that is coupled to
      nitric oxide release in its nervous and immune tissues: Evidence for
      neurotransmitter and hormonal signaling.
AB  - OBJECTIVES: The study was designed to determine if morphine was present in
      lobster tissues. It was also important to determine, as in other animals, if its
      levels would change in response to stress. In this regard, it was also important
      to determine if lobster immune and neural tissues express the mu opiate receptor
      subtype, which was coupled to constitutive nitric oxide synthase derived nitric
      oxide release. METHODS: Homarus americanus were used in these experiments.
      Morphine was purified in lobster tissues via high pressure liquid chromatography
      coupled to UV detection. It was quantified via radioimmunoassay (RIA) and was
      identified via quadruple time of flight - mass spectrometry. Animals were subject
      to 2 forms of trauma, namely pereiopod-ablation or lipopolysaccaride (LPS) -
      injection, and morphine levels determined in nerve cord or hemolymph. Real-time
      nitric oxide production was determined via an amperometric probe. RT-PCR was used
      to determine the presence of a micro opiate receptor transcript. RESULTS: In
      Homarus americanus hemolymph and nerve cord morphine was found. RIA revealed
      morphine levels of 3.36 pg/mg +/ - 0.48 SEM (N=8) in nerve cord and 717.88 pg/ml
      +/ - 56.77 SEM (N=58) in hemolymph. In stressed (pereiopod-ablated or LPS
      injected) animals, the endogenous morphine levels initially increased
      significantly by 24% for hemolymph and 48% for nerve cord. By day 5, the stressed
      and control values for endogenous morphine, in both tissues, was lower and non
      distinguishable. In both hemocytes and neural cells, morphine, not met
      enkephalin, stimulated constitutive nitric oxide release in a naloxone
      antagonizable manner, demonstrating a mu opiate receptor mediated phenomenon and
      suggesting the presence of the mu opiate receptor subtype, micro3, since it is
      opiate alkaloid selective and opioid peptide insensitive. RT-PCR revealed the
      presence of a micro opiate receptor transcript in Homarus neural and immune
      tissues, which exhibits a 100% sequence identity with its human counterpart.
      CONCLUSION: Taken together, after eliminating all sources of contamination,
      morphine is present in lobster tissues, potentially demonstrating hormonal and
      neurotransmitter functions that are involved in the animals' stress response.

PMID- 15855880
TI  - Association between human leukocyte antigen (HLA) and interferon- induced thyroid
      diseases in four patients with HCV-related chronic hepatitis.
AB  - OBJECTIVES: The interferon-alpha (IFN-alpha) therapy for HCV hepatitis may
      exacerbate or induce underlying thyroid disorders. Besides viral factors, the
      human leukocyte antigen (HLA) may be an independent risk factor. METHODS: We
      evaluated fifteen patients with HCV chronic hepatitis during a period of 40
      months. At the enrollment, all the patients were negative for thyroid disorders,
      excluding one patient with subclinical hypothyroidism. Eleven patients received
      IFN-alpha therapy. The HLA system was examined in every patient, evaluating
      antigens (n=40) of locus A, B and Cw and alleles (n=19) of locus DRB1* and DQB1*.
      The HLA system was also examined in healthy subjects (n=107) as a control group.
      RESULTS: The HCV genotype distribution in patients was: 1b=20%, 2a=60%, 3a=20%.
      Four IFN-treated patients presented clinical thyroid disorders, including
      autoimmune hypothyroidism (n=2), transient thyrotoxicosis (n=1) and subacute
      thyroiditis (n=1). The HLA susceptibility to thyroid disorders (antigen/allele
      frequency) in the whole group of patients was not different in respect to
      controls and normal Italian population. The patients with HCV chronic hepatitis
      that developed thyroid diseases after IFN- treatment had a double and specific
      association with the HLA system (Mantel-Haenszel X(c)(2)=4.706, p<0.05).
      CONCLUSIONS: This case report suggests that HLA system examination is an
      important and promising diagnostic aspect that may be considered in order to
      evaluate the appearance of thyroid disorders during the IFN-alpha treatment for
      HCV-related chronic hepatitis.

PMID- 15855881
TI  - Inhibitory effects of adrenomedullary hormone on the induction and growth of
      fibrosarcoma by methylcholanthrene.
AB  - OBJECTIVE: Effects of adrenomedullary hormone(s) on the induction and growth of
      fibrosarcoma by methylcholanthrene (MC) were examined. METHODS: At 28 days of
      age, male Wistar rats were divided into four groups: 1) control, 2) bilateral
      adrenomedullectomy (Bil. AMX), 3) right AMX + left adrenomedullary
      autotransplantation (AMX + AMT), 4) Bil. AMX + epinephrine injection (Bil. AMX +
      E) groups. 14 days after surgery, MC crystals were inserted underneath the dorsal
      skin, and in the Bil. AMX + E group, epinephrine was injected subcutaneously,
      twice every week. RESULTS: The incidence of tumor at 90 days after the MC
      injection was 8 per 35 cases (22.9%) in the control group, 12 per 36 cases
      (33.3%) in the AMX + AMT group, 8 per 28 cases (28.6%) in the Bil. AMX + E group,
      and each value was lower compared with that of the Bil. AMX group, 24 per 34
      cases (70.6 %), (P<0.001, P<0.002, P<0.005). Such differences among groups were
      not seen at 165 days after the injection of MC. DISCUSSION: The mechanisms of
      effects of AMX, AMT and/or epinephrine on the tumor incidence have been discussed
      with reference to tumor promotion, vascular neoplasia, etc. Since norepinephrine
      remaining in the blood of AMX rats was ineffective, at least it is likely that
      this inhibitory effect of epinephrine is mediated via the beta2-receptor.
      CONCLUSION: The results suggest that adrenomedullary hormone, probably
      epinephrine, has inhibitory effects on the induction and growth of fibrosarcoma
      by MC, particularly in the early stage.

PMID- 15855882
TI  - Influence of maternal testosterone on the strategies in the open field behaviour
      of rats.
AB  - OBJECTIVES: The purpose of the present study was to characterize the influence of
      testosterone administered to pregnant females on offsprings postnatal behavioral
      strategies in the open field. METHODS: The influence of maternal testosterone on
      behaviour of 23 day old male and female offsprings was studied in a 20-minute
      open field test. A total of 9 behavioural events were compared between a control
      (male n=12, female n=8) and a testosterone group (male n=9, female n=9). Dynamics
      and patterns of association of these behavioural events were analyzed. The
      testosterone group was prenatally exposed to testosterone (a single intramuscular
      injection of 2.5 mg testosteroni isobutyras on gestation day 14). RESULTS: Male
      offsprings exposed prenatally to testosterone displayed significantly high levels
      of ambulation (P<0.05), sniffing (P<0.01), sniffing the air (P<0.05), urination
      (P<0.05) and significantly lower level of vocalization (P<0.05) than control.
      Female offsprings exposed prenatally to testosterone displayed significantly
      higher level of sniffing the air (P<0.05) than control. Significant differences
      in the dynamics of habituation process were registered only in the group of male.
      They were from 5 to 10 min in ambulation (P<0.05), from 10 to 15 min in sniffing
      (P<0.05) and vocalization (P<0.05), from 10 to 15 min and from 15 to 20 min in
      sniffing the air (P<0.05) and from 0 to 5 min in defecation (P<0.05) and
      urination (P<0.01). CONCLUSION: Our results suggest that maternal testosterone
      may influence especially male postnatal open field strategies.

PMID- 15855883
TI  - Effects of prolactin on hypothalamic supraoptic neurones: evidence for modulation
      of STAT5 expression and electrical activity.
AB  - OBJECTIVES: The study investigated the role of prolactin (PRL) in modulating
      STAT5 and electrical activity of magnocellular neurones in the supraoptic (SO)
      nucleus of male rats. METHODS: Evidence of expression of STAT5 in the SO nucleus
      was investigated by immunocytochemical methods. Effect of blocking prolactin
      receptors on STAT 5 expression was investigated by Western blotting following
      transfection of SO neurones with a dominant negative mutant form of the PRL
      receptor. Prolactin-induced changes in electrical activity were investigated by
      extracellular recording in hypothalamic slices. RESULTS: A high proportion of SO
      neurones in male rats expressed immunoreactive STAT5. Levels of activated STAT5
      within the SO nucleus of PRL-treated rats was reduced following transfection with
      a dominant negative mutant form of the PRL receptor, as compared to rats
      transfected with wild type PRL receptor. Electrophysiological recordings from the
      SO nucleus in horizontal brain slices showed that approximately 25% of neurones
      were responsive to PRL, with both inhibitory and excitatory effects being
      observed. Cells displaying PRL responses included pharmacologically-identified
      oxytocinergic neurones. CONCLUSIONS: Collectively, the results suggest that
      central PRL targets neurones of the SO nucleus, influencing both activation of
      the JAK-STAT signalling pathway and neuronal excitability. Whilst the functional
      significance of this interaction remains to be established, it might be important
      in co-ordinating oxytocin secretion with physiological events associated with
      changes in plasma PRL, or in mediating a feedback loop in the oxytocinergic
      regulation of lactotrophs.

PMID- 15855884
TI  - Treatment of autoimunne ovarian damage in adolescent girls.
AB  - INTRODUCTION: To investigate levels of antiovarian autoantibodies in girls and
      young women with disturbances of menstrual cycle before and during treatment with
      hormonal therapy. To explain morphological changes in ovarian structure in these
      patients. MATERIAL AND METHODS: Studied group included 39 patients. 18 patients
      were treated for primary amenorrhoea, 21 for menstrual cycle disorders. Patients
      included in the study were repeatedly examined at the beginning of the study and
      after six months during which they were treated by estrogen and gestagen. In all
      patients we have tested FSH, LH and FSH/LH ratio, presence of antiovarian
      antibodies. Results were compared with those obtained in control women. 21
      antiovarian antibodies positive patients were indicated for laparoscopic biopsy.
      Bioptic sample was examined using light and electron microscopy. RESULTS: Our
      treatment with hormonal therapy lead to the reduction of ovarian antigens. In 85%
      of the cases marked decrease of antiovarian autoantibodies levels was observed,
      while in 28% of the cases the levels were undetectable. From morphological
      changes of the bioptic sample enhanced atresia of follicules at different
      developmental stages was frequently observed. It evoked marked reduction of
      follicular apparatus up to its complete disappearing. CONCLUSION: The results of
      our study and mapping of the antiovarian antibodies positivity support our
      hypothesis that the antiovarian antibodies positivity corresponds with the
      clinical symptoms. Appropriate treatment with hormonal replacement therapy
      minimizes ovarian destruction, preserves ovarian hormonal functions and saves
      healthy ovarian tissue necessary for future fertility.

PMID- 15855885
TI  - Urinary 6-sulfatoxymelatonin excretion in humans during domestic exposure to 50
      hertz electromagnetic fields.
AB  - OBJECTIVES: Exposure to extremely low frequency electromagnetic fields (ELF-EMF)
      has been suggested to suppress melatonin secretion, which might result in higher
      cancer risks because of its missing oncostatic action. We investigated the
      effects of residential exposure to ELF-EMF on the excretion of urinary 6
      sulfatoxymelatonin (6-OHMS), the major melatonin metabolite, as an indicator of
      nocturnal melatonin secretion. METHODS: 6-OHMS was measured in two spot urine
      samples, collected at 22.00 h and 08.00 h, in 29 men and 22 women. Spot ELF-EMF
      measurements were conducted at the centre and the four angles of the living room,
      the bedroom, and the kitchen of study subjects at low current configuration (all
      lights and appliances turned off), and they were repeated immediately at high
      current configuration (all lights and appliances turned on). RESULTS: Risk of a
      reduced 6-OMHS nocturnal secretion was elevated for daily alcohol intake (OR =
      6.4; 95%C.I. 1.4,33.1), and body mass index (BMI) above the median (OR = 2.2;
      95%C.I. 0.5,9.6). Risk of disrupted rhythm of 6-OHMS excretion was moderately
      elevated for domestic ELF-EMF exposure above the upper tertile at low current
      configuration (OR = 2.6; 95%C.I. 0.4,15.7). CONCLUSION: Alcohol consumption, BMI,
      and gender seem to affect nocturnal melatonin secretion, while an effect of
      residential exposure to ELF-EMF is uncertain. Future studies should properly
      account for the effect of such variables, when addressing the hypothesis of
      disturbances in melatonin secretion as a plausible explanation for the reported
      excess risk of several tumoral diseases associated with low level ELF-EMF
      exposure.

PMID- 15855886
TI  - Spinal cord lesions in diabetes mellitus. Somatosensory and motor evoked
      potentials and spinal conduction time in diabetes mellitus.
AB  - OBJECTIVES: Diabetic neuropathy and autonomic nervous system neuropathy are
      recognized as the most common clinical pictures of nervous system disorders
      caused by diabetes mellitus (DM). Damage to the brain and the spinal cord is
      rare. The aim of this work is to show the importance of somatosensory and motor
      evoked potentials (SEP and MEP) for the early diagnosis of nervous system damage
      related to diabetes mellitus. MATERIAL AND METHODS: We examined spinal and
      cortical somatosensory evoked potentials (SEP) after median and fibular nerve
      stimulation in diabetics and control subjects. We measured the latencies of
      individual wave deflections and peripheral and central conduction time (PCT and
      CCT) of spinal and cortical SEP. Similarly, transcranial magnetic stimulation was
      used for measuring the central and peripheral conduction time (CCT and PCT) in a
      group of type 1 diabetics and a control group of volunteers. RESULTS: The
      examination SEP and MEP proved and confirmed the prolongation not only of
      peripheral conduction time, but also of the central conduction time - especially
      in spinal cord structures. An assumption that spinal cord changes are connected
      with the decreased number of myelinated fibers able to conduct the impulses from
      periphery and brain cortex, respectively, has to be accepted. CONCLUSIONS: The
      results suggest that the use of somatosensory and motor evoked potentials (SEP
      and MEP) examination and conduction times measurement has significance in the
      confirmation of unapparent lesions of the spinal cord in diabetics of both types.

PMID- 15855887
TI  - Investigation of serum leptin levels in professional male football players and
      healthy sedentary males.
AB  - OBJECTIVE: In the present study we aimed at investigating leptin levels in
      professional male athletes who have been exercising regularly for a long time and
      leptin levels in healthy sedentary males. METHODS: The study included 10 male
      professional football players and 17 healthy sedentary males. The relations
      between groups in terms of leptin levels, Max VO2 levels, blood lactic acid
      levels before and after exercise and effort durations were investigated. RESULTS:
      It was found in the study that although BMI of professional male athletes was
      higher than that of the healthy sedentary males, leptin levels of the former were
      significantly lower (p<0.01), while VO2Max levels (p<0.05) and test periods
      (p<0.01) were significantly higher than those in the latter. As for lactic acid
      levels after exercise and between groups, these were also higher in athletes, but
      the difference was not statistically significant (p>0.05). CONCLUSION: Leptin
      levels of those who exercised regularly were found lower than the levels in
      healthy males. Although the increase in serum leptin levels is in direct
      proportion with BMI in general, the major determinant of serum leptin level is
      the body fat rate. As regular exercising reduces body fat rate, it also reduces
      serum leptin levels.

PMID- 15855888
TI  - Gender-related differences in prolactinomas. A clinicopathological study.
AB  - BACKGROUND/AIMS: Prolactinomas are the most common tumors of the pituitary gland.
      Only few studies have documented gender-related differences in the growth and
      presentation of these tumors, but nothing is known about their effects on their
      subsequent surgical outcome and prognosis. PATIENTS & METHODS: Twenty-six
      patients with prolactinomas, that met strict immunohistochemical and electron
      microscopic criteria and were surgically treated between January 1990 and June
      1997, were retrospectively reviewed. The patient charts, as well as histological
      (mitotic index) immunohistological (MIB-1 labeling-index) and electronic
      microscopical staining were analyzed. RESULTS: Nineteen patients were women, and
      seven were men; the female-to-male-ratio was 2.7:1. Men were significantly older,
      both at diagnosis and surgery. Menstrual abnormalities were the most common
      presenting symptom in women, whereas impotence predominated in men. Psychological
      symptoms were significantly more common in men than in women. Men had a
      significantly shorter preoperative duration of symptoms and higher preoperative
      serum prolactin levels than women. The preoperative prolactin levels and
      proliferative activities (mitotic index, MIB-1 labeling index) were lower in
      women compared to men and showed a direct correlation to postoperative outcome.
      The overall outcome was significantly better in women than in men. In women, age
      less than 35 years was a beneficial prognostic factor, and preoperative
      bromocriptine treatment was associated with a significantly worse long-term
      outcome. CONCLUSION: The biology and the clinical course of prolactinomas seem to
      differ in women and men. In men, the preoperative durations of symptoms is
      shorter, the tumors are larger and more invasive at surgery, and the outcome is
      worse than in women. Based on proliferative activities (mitotic index, MIB-1
      labeling index), the predominance of marcoadenomas in men is due to a high
      frequency of rapidly growing tumors, which are often invasive and frequently
      correlated with a worse outcome. Our findings may justify a more aggressive
      therapeutic approach to prolactinomas in men than in women.

PMID- 15855889
TI  - Targeted therapy: the fast pace of progress.

PMID- 15855890
TI  - Molecularly targeted therapies for breast cancer.
AB  - BACKGROUND: The management of patients with localized and advanced breast cancer
      continues to evolve. Chemotherapy, endocrine therapy, and trastuzumab are
      effective therapies but leave considerable room for improvement. As the cellular
      aberrations inherent to cancer cells in general and breast cancer cells
      specifically are better understood, therapies to target specific cellular
      pathways continue to be developed with the goal of expanding available effective
      therapy through better patient selection. METHODS: We conducted a computerized
      search of the medical literature as well as a manual search of selected meeting
      abstracts. RESULTS: Several targeted therapies are in phase III clinical trials
      testing their promise in the treatment of breast cancer. Many other agents are
      completing phase I and II testing. An overview of the most promising agents in
      clinical development is discussed herein. CONCLUSIONS: Targeted therapy for
      breast cancer is a reality at this time, and several new agents hold promise for
      expanding and refining the pool of patients likely to further benefit from this
      approach in the near future.

PMID- 15855891
TI  - Targeted therapy for hematologic malignancies.
AB  - BACKGROUND: The introduction of monoclonal antibodies, either as native molecules
      or conjugated to radioisotopes or other toxins, has led to new therapeutic
      options for patients with hematologic malignancies. In addition, the use of small
      molecules against specific cell surface receptors, enzymes, and proteins has
      become an important strategy in the treatment of such disorders. METHODS: The
      author reviewed the published clinical trials of monoclonal antibody and other
      targeted therapies in hematologic malignancies. RESULTS: Results from several
      trials demonstrate a therapeutic benefit for the use of monoclonal antibodies
      (either native or conjugated) and other targeted therapies, used alone or in
      combination with standard cytotoxic chemotherapy. CONCLUSIONS: Targeted therapy
      of hematologic malignancies seems to be an effective and less toxic approach to
      the treatment of such disorders. Nevertheless, additional studies are needed to
      determine where and when such management fits into a therapeutic regimen for any
      given disorder, whether upfront or as salvage therapy, alone or in combination
      with chemotherapy (concurrent or sequential).

PMID- 15855892
TI  - Targeted therapy in multiple myeloma.
AB  - BACKGROUND: Multiple myeloma (MM) is an incurable malignancy. Recent insights
      into its biology has allowed the use of novel therapies targeting not only the
      deregulated intracellular signaling in MM cells but also its interaction with the
      bone marrow microenvironment that confers drug resistance, growth, and survival
      advantage to the malignant cells. METHODS: We review and summarize the recent
      advances in our knowledge of myeloma biology as well as the mechanism of action
      and clinical efficacy for novel therapeutic agents in clinical trials. RESULTS:
      Several novel therapeutic agents are currently in clinical trials. Thalidomide is
      already established for both initial and salvage treatment. Bortezomib is being
      tested alone and in combination with conventional chemotherapy in various
      settings. Other agents are less effective in producing response but have been
      able to stabilize disease in patients with relapsed and/or refractory disease,
      such as arsenic trioxide, farnesyltransferase inhibitors, 2-methoxyestradiol, and
      vascular endothelial growth factor receptor inhibitors. Insights into drug
      resistance mechanism have also led to the development of novel agents that
      sensitize myeloma cells to chemotherapy (Bcl-2 antisense). Gene expression
      studies have in many instances identified pathways other than the intended target
      of the drug and have provided insights into the therapeutic mechanisms.
      CONCLUSIONS: In the future, patients with MM will have more therapeutic options
      available than ever before. The challenge will be to identify patient subgroups
      that will benefit most from the different therapies and then determine how these
      biologically based therapies could be combined and incorporated into the overall
      management of patients.

PMID- 15855893
TI  - Targeted therapies in the treatment of colorectal cancers.
AB  - BACKGROUND: In solid organ malignancies, no tumor type has seen a greater impact
      from the development of novel targeted therapies in 2004 than metastatic
      colorectal cancer. METHODS: We review the current progress to date with the use
      of monoclonal antibodies in colorectal cancer and look at newer therapies under
      investigation. RESULTS: Two monoclonal antibodies received Food and Drug
      Administration approval in early 2004, both for the indication of advanced,
      metastatic colorectal cancer. A large, randomized, placebo-controlled study
      demonstrated that the addition of a monoclonal antibody to vascular endothelial
      growth factor, bevacizumab, led to a statistically significant improvement in
      overall survival, with tolerable additional toxicity. Chimeric monoclonal
      antibody therapy directed at the epidermal growth factor receptor was associated
      with radiographic responses in a significant minority of patients with irinotecan
      refractory colon cancer in a randomized phase II study of patients with
      irinotecan-refractory disease. CONCLUSIONS: These dramatic successes have led to
      further clinical studies of targeted therapy in colorectal cancer, making it one
      of the most promising areas of cancer research.

PMID- 15855894
TI  - Imaging gastrointestinal stromal tumors.
AB  - BACKGROUND: Because of the recent reclassification of mesenchymal tumors, which
      was based on a better understanding of the genetics and immunophenotype of
      gastrointestinal stromal tumors (GISTs), only a limited number of studies have
      described the radiologic appearance of GISTs. METHODS: This study reviews the
      imaging characteristics of GISTs, with an emphasis on differentiating benign and
      malignant tumors using positron emission tomography (PET), computed tomography
      (CT), and magnetic resonance imaging (MRI). We reviewed the data from 53 cases of
      GISTs treated at our institute. The imaging studies from these cases, which were
      recorded at our institute from January 1998 through June 2003, included PET, CT,
      and MRI. RESULTS: Of the 53 GIST cases, stomach and small bowel tumors accounted
      for 80% of the tumors. Malignant lesions were larger and more heterogeneous, had
      ulcerations, and were PET positive. Peritoneal and liver metastases were most
      common. CONCLUSIONS: PET, CT, and MRI appear to be useful in differentiating
      nonmetastasizing from malignant GISTs.

PMID- 15855895
TI  - Small molecule and monoclonal antibody therapies in neurooncology.
AB  - BACKGROUND: The prognosis for most patients with primary brain tumors remains
      poor. Recent advances in molecular and cell biology have led to a greater
      understanding of molecular alterations in brain tumors. These advances are being
      translated into new therapies that will hopefully improve the prognosis for
      patients with brain tumors. METHODS: We reviewed the literature on small molecule
      targeted agents and monoclonal antibodies used in brain tumor research and brain
      tumor clinical trials for the past 20 years. RESULTS: Brain tumors commonly
      express molecular abnormalities. These alterations can lead to the activation of
      cell pathways involved in cell proliferation. This knowledge has led to interest
      in novel anti-brain-tumor therapies targeting key components of these pathways.
      Many drugs and monoclonal antibodies have been developed that modulate these
      pathways and are in various stages of testing. CONCLUSIONS: The use of targeted
      therapies against brain tumors promises to improve the prognosis for patients
      with brain tumors. However, as the molecular pathogenesis of brain tumors has not
      been linked to a single genetic defect or target, molecular agents may need to be
      used in combinations or in tandem with cytotoxic agents. Further study of these
      agents in well-designed cooperative clinical trials is needed.

PMID- 15855896
TI  - Breast cancer susceptibility and the DNA damage response.

PMID- 15855897
TI  - The "total cancer care" concept: linking technology and health care.

PMID- 15855898
TI  - Manual therapy in children: proposals for an etiologic model.

PMID- 15855900
TI  - Questioning the importance of authorship.

PMID- 15855899
TI  - Conservative treatment of a patient with previously unresponsive whiplash
      associated disorders using clinical biomechanics of posture rehabilitation
      methods.
AB  - OBJECTIVE: To describe the treatment of a patient with chronic whiplash
      associated disorders (WADs) previously unresponsive to multiple physical therapy
      and chiropractic treatments, which resolved following Clinical Biomechanics of
      Posture (CBP) rehabilitation methods. CLINICAL FEATURES: A 40-year-old man
      involved in a high-speed rear-impact collision developed chronic WADs including
      cervicothoracic, shoulder, and arm pain and headache. The patient was diagnosed
      with a confirmed chip fracture of the C5 vertebra and cervical and thoracic disk
      herniations. He was treated with traditional chiropractic and physical therapy
      modalities but experienced only temporary symptomatic reduction and was later
      given a whole body permanent impairment rating of 33% by an orthopedic surgeon.
      INTERVENTION AND OUTCOME: The patient was treated with CBP mirror-image cervical
      spine adjustments, exercise, and traction to reduce forward head posture and
      cervical kyphosis. A presentation of abnormal head protrusion resolved and
      cervical kyphosis returned to lordosis posttreatment. His initial neck disability
      index was 46% and 0% at the end of care. Verbal pain rating scales also improved
      for neck pain (from 5/10 to 0/10). CONCLUSION: A patient with chronic WADs and
      abnormal head protrusion, cervical kyphosis, and disk herniation experienced an
      improvement in symptoms and function after the use of CBP rehabilitation
      protocols when other traditional chiropractic and physical therapy procedures
      showed little or no lasting improvement.

PMID- 15855901
TI  - The Nordic back pain subpopulation program: can patient reactions to the first
      chiropractic treatment predict early favorable treatment outcome in nonpersistent
      low back pain?
AB  - OBJECTIVE: To investigate whether 3 distinct patterns of reactions to
      chiropractic care can predict early favorable treatment outcome in patients with
      nonpersistent low back pain (LBP). DESIGN: Multicenter practice-based predictive
      validity study. STUDY SUBJECTS: Sixty private practice chiropractors in Sweden
      recruited a maximum of 20 consecutive patients with LBP each, with a duration of
      less than 2 weeks at the time of consultation and a maximum of 30 days totally
      over the past year. METHODS: Chiropractic management was decided on by the
      treating chiropractor. The outcome variable was self-reported "definite
      improvement" at the fourth visit. The predictor variables included 3 hypothesized
      prognostic groups (best, intermediate, and least favorable) on the basis of
      clinical information collected at baseline and at the second visit. The
      covariates included age, sex, pain intensity during the past 24 hours,
      description of disability, duration and pattern of pain during the present
      attack, and duration and pattern of pain during the past 12 months. The 3
      predictor groups were cross-tabulated against the outcome variable and the other
      covariates. Backward stepwise logistic regression was performed to test for
      confounding or modification from relevant covariates. RESULTS: Information was
      provided on 708 patients, of which 674 questionnaires were valid. Of the 223
      patients in the hypothesized best prognostic group, 91% (95% CI, 79-100) reported
      to be "definitely improved" by the fourth visit, vs 76% (72-80) of the 420
      patients in the intermediate prognostic group, and 36% (19-53) of the 31 patients
      in the least favorable prognostic group. These results were not altered after
      controlling for the covariates. CONCLUSION: For chiropractic patients with
      nonpersistent LBP, these findings show that it is possible to predict already by
      the second visit which patients may or may not report improvement at the fourth
      visit.

PMID- 15855902
TI  - The effect of low force chiropractic adjustments for 4 weeks on body surface
      electromagnetic field.
AB  - OBJECTIVE: To study the effects of 4 weeks of low-force chiropractic adjustments
      on body surface electromagnetic fields (EMFs). METHOD: Thirty-five chiropractic
      students randomly assigned into control (17 subjects) and experimental groups (28
      subjects). A triaxial fluxgate magnetometer was used for EMF detection. The
      subjects' body surface EMF was determined in the prone position before and after
      the chiropractic adjustment. A Toftness low-force chiropractic adjustment was
      applied to the cervical, thoracic, lumbar, and sacral areas as determined by the
      practitioner. Heart rate variability analysis was recorded once a week to
      determine autonomic nervous system activity in both the control and experimental
      groups. RESULTS: The EMF on the subjects' body surface decreased after
      chiropractic adjustment at the cervical, thoracic, lumbar, and sacral regions in
      all 6 visits during the 4-week treatment period. The EMF showed a downtrend over
      the 4-week period after the low-force adjustment. The same changes were not
      observed in the control group. The chiropractic adjustment group had a slight
      decrease in heart rate over the 4-week treatment period, and no significant
      change was observed in the control group. Heart rate variability analysis did not
      show consistent changes before and after the low-force adjustments during the
      treatment period. CONCLUSION: Low-force chiropractic adjustment in the cervical
      and thoracic areas resulted in a consistent reduction of the body surface EMF
      after 4 weeks of active treatment. No statistically significant differences were
      found in the heart rate and heart rate variability in the 4-week study.

PMID- 15855903
TI  - The selection effects of the inclusion of a chiropractic benefit on the patient
      population of a managed health care organization.
AB  - OBJECTIVE: The aim of this study is to measure the selection effects of the
      inclusion of a chiropractic benefit on a managed care health plan. DESIGN: An
      analysis of enrollment data from a managed care health plan over a 4-year period
      was conducted. Employers could select the managed care plan with or without a
      chiropractic care benefit. Comparisons of demographic and comorbid
      characteristics were made between employees who had the chiropractic benefit and
      those who did not, and between individuals who self-selected chiropractic care
      and those who self-selected medical care. RESULTS: The cohort with chiropractic
      coverage was younger with fewer subjects in the older age group (>65 years; 6.5%
      vs 9.6%) and more subjects in the younger age group (0-17 years; 31.9% vs 26.2%).
      The mean age of the group with coverage was 32.9 compared with 35.5 in the group
      without coverage. Comparing self-selected chiropractic patients to self-selected
      medical patients, there were fewer subjects older than 65 years in the
      chiropractic group (4.9% vs 9.2%) and fewer subjects aged 0 to 17 years (9.4% vs
      19.4%). In 6 of the 8 comorbid conditions studied, the rates were lower in the
      cohort with chiropractic coverage compared with the group without coverage. The
      rates of comorbid conditions in self-selected chiropractic patients were lower in
      all 8 categories compared with self-selected medical patients. CONCLUSION: The
      inclusion of a chiropractic benefit in a health plan produces a modest favorable
      selection processes resulting in a slightly younger patient population with fewer
      comorbidities. At the level of patient self-selection, chiropractic patients are
      considerably younger and healthier than comparable medical patients.

PMID- 15855904
TI  - Interprofessional referral patterns in an integrated medical system.
AB  - OBJECTIVE: To determine the interreferral patterns among physicians and
      complementary and alternative medicine (CAM) providers in an independent practice
      association integrated medical system. METHOD: Data from a 1-year period were
      collected on referral patterns, diagnosis, number of visits, cost, and
      qualitative aspects of patient care. The independent practice association
      provided care for approximately 12,000 patients. RESULTS: In the selected
      integrative network, there are those primary care physicians (PCPs) who refer and
      those who do not. Among those PCPs that refer to CAM, a preference is shown for a
      limited number of providers to whom they refer. Although doctors of chiropractic
      get more referrals, they are also more concentrated among selected providers than
      are doctors of oriental medicine. CONCLUSION: This study shows the interreferral
      patterns among the PCP and CAM providers working within an integrated medical
      system. One effect of being in the network for doctors of chiropractic and
      doctors of oriental medicine might be the possible interreferrals between each
      other.

PMID- 15855905
TI  - Predictive efficacy of Chiropractic College Assessment Test scores in basic
      science chiropractic education.
AB  - OBJECTIVE: To evaluate the ability of Chiropractic College Assessment Test (CCAT)
      to explain academic success within a chiropractic basic science curriculum.
      METHODS: The CCAT examination was administered to 202 subjects from 1
      chiropractic college on the first day of classes. Zero-order Pearson correlations
      were used to examine for associations between the prechiropractic grade point
      average (GPA), CCAT scores, and basic science GPA. Multiple regression techniques
      were applied to determine the predictive efficacy of CCAT scores on basic science
      GPA. RESULTS: Study results indicate a correlation between prechiropractic GPA,
      CCAT scores (r = 0.348, P < .001), and basic science GPA (r = 0.559, P < .001).
      Correlation was also noted between CCAT scores and basic science GPA (r = 0.537,
      P < .001). Using multiple regression, together the variables (age, postsecondary
      education, prechiropractic GPA, and CCAT scores) accounted for a significant
      portion (R2 = 0.483, P < .001) of the total variance in basic science GPA.
      Furthermore, the CCAT scores accounted for significant unique explanation (change
      R2 = 0.081, P < .001) beyond that offered by the traditionally used
      prechiropractic GPA. CONCLUSION: The CCAT examination provides a valuable a
      priori indicator of success within the basic science curriculum of this
      particular chiropractic program. Consideration should be given to adopting the
      CCAT examination as one of a number of heuristic guides students and college
      officials use in making enrollment decisions.

PMID- 15855906
TI  - Insomnia: does chiropractic help?
AB  - OBJECTIVE: To evaluate the effect of chiropractic care on insomnia. DESIGN:
      Tripartite pilot study. METHODS: The expectations of the chiropractic community
      were canvassed, a retrospective study to recall changes in sleep patterns was
      undertaken, and a prospective pilot study to monitor sleep patterns after
      chiropractic care was carried out. Convenience sampling was used. RESULTS: The
      221 patients and 15 chiropractors who completed the expectation study tended to
      believe that patients with sleeping difficulties benefited from chiropractic
      care. The chiropractors were more guarded in their expectations than
      participating patients. One third of the 154 patients who completed the
      semistructured interview reported their sleep pattern was changed immediately
      after their chiropractic adjustment. All but 1 of these 52 patients reported
      improvement. Twenty patients with insomnia participated in the prospective study.
      Although compared with the report in their screening questionnaire, improvement
      was noted in certain sleep parameters in the 6 days after their adjustment, no
      temporal trends emerged in the days and/or weeks after the chiropractic
      consultation. Most patients reported experiencing less or no discomfort during
      the duration of the study. CONCLUSION: Although a number of patients do perceive
      chiropractic care offers temporary respite from their insomnia problem, when
      changes were more objectively monitored, improvements were erratic and no
      consistent temporal trends were detectable. Convincing evidence has yet to be
      produced before routine chiropractic care can be considered adequate intervention
      for patients with sleeping difficulties. More definitive answers may result from
      future research being undertaken in sleep laboratories.

PMID- 15855907
TI  - Determining the relationship between cervical lordosis and neck complaints.
AB  - OBJECTIVE: To investigate the presence of a "functionally normal" cervical
      lordosis and identify if this and the amount of forward head posture are related
      to neck complaints. METHODS: Using the posterior tangent method, an angle of
      cervical lordosis was measured from C2 through C7 vertebrae on 277 lateral
      cervical x-rays. Anterior weight bearing was measured as the horizontal distance
      of the posterior superior body of the C2 vertebra compared to a vertical line
      drawn superiorly from the posterior inferior body of the C7 vertebra. The
      measurements were sorted into 2 groups, cervical complaint and noncervical
      complaint groups. The data were then partitioned into age by decades, sex, and
      angle categories. RESULTS: Patients with lordosis of 20 degrees or less were more
      likely to have cervicogenic symptoms (P < .001). The association between cervical
      pain and lordosis of 0 degrees or less was significant (P < .0001). The odds that
      a patient with cervical pain had a lordosis of 0 degrees or less was 18 times
      greater than for a patient with a noncervical complaint. Patients with cervical
      pain had less lordosis and this was consistent over all age ranges. Males had
      larger median cervical lordosis than females (20 degrees vs 14 degrees) (2-sided
      Mann-Whitney U test, P = .016). When partitioned by age grouping, this trend is
      significant only in the 40- to 49-year-old range (2-sided Mann-Whitney U test, P
      < .01). CONCLUSION: We found a statistically significant association between
      cervical pain and lordosis < 20 degrees and a "clinically normal" range for
      cervical lordosis of 31 degrees to 40 degrees. Maintenance of a lordosis in the
      range of 31 degrees to 40 degrees could be a clinical goal for chiropractic
      treatment.

PMID- 15855908
TI  - Symptomatic expansile vertebral hemangioma causing conus medullaris compression.
AB  - OBJECTIVE: To present a case of symptomatic, expansile L1 vertebral hemangioma.
      CLINICAL FEATURES: A 46-year-old man presented with progressive neurologic
      changes and insidious onset of low back pain. INTERVENTION AND OUTCOME: After a
      trial of 3 visits of conservative chiropractic care, no improvement was noted.
      Magnetic resonance imaging was obtained, revealing an expansile hemangioma with
      extra-osseous component compromising the conus medullaris at the level of the L1
      lumbar vertebra. Neurosurgical intervention resulted in clinical improvement.
      CONCLUSION: Primary care physicians treating patients with low back pain should
      be aware of neurologic red flags requiring prompt attention. Magnetic resonance
      imaging is the imaging modality of choice when evaluating a neurologic
      abnormality presumably related to a space-occupying lesion. Although a disk
      herniation is the most common cause of these symptoms, clues in the history and
      examination must prompt physicians to expand their differential diagnosis to
      include a variety of other extradural masses.

PMID- 15855909
TI  - Treatment of a case of subacute lumbar compartment syndrome using the Graston
      technique.
AB  - OBJECTIVE: To discuss subacute lumbar compartment syndrome and its treatment
      using a soft tissue mobilization technique. CLINICAL FEATURES: A patient
      presented with low back pain related to exercise combined with prolonged flexion
      posture. The symptoms were relieved with rest and lumbar extension. The patient
      had restrictive lumbar fascia in flexion and rotation and no neurological
      deficits. INTERVENTION AND OUTCOME: The restrictive lumbar posterior fascial
      layers and adjoining restrictive fascia (thoracic, gluteal, hamstring) were
      treated with a form of instrument-assisted soft tissue mobilization called the
      Graston technique. Restoration of fascial extensibility and resolution of the
      complaint occurred after 6 treatment visits. CONCLUSIONS: The posterior spinal
      fascial compartments may be responsible for intermittent lower back pain.
      Functional clinical tests can be employed to determine whether the involved
      fascia is abnormally restrictive. Treatment directed at the restrictive fascia
      using this soft tissue technique may result in improved fascial functional
      testing and reduction of symptoms.

PMID- 15855910
TI  - A proposed method for estimating the efficiency and effectiveness of techniques
      of musculoskeletal therapy.

PMID- 15855912
TI  - Health care for our bones: a practical nutritional approach to preventing
      osteoporosis.

PMID- 15855918
TI  - Gene therapy: the good, the bad, and the ugly.

PMID- 15855919
TI  - Electrostimulation for the prevention of deep venous thrombosis in patients with
      major trauma: a prospective randomized study.
AB  - BACKGROUND: Current methods of posttraumatic thromboprophylaxis (heparins and
      sequential compression devices) are inadequate. New methods should be tested.
      Muscle electrostimulation (MEST) has been used over the years with mixed-but
      predominantly encouraging-results for a variety of conditions, including
      prevention of deep venous thrombosis (DVT). It has not been tested in multiple
      trauma patients. METHODS: Trauma patients with Injury Severity Score higher than
      9 who were admitted to the intensive care unit and had a contraindication for
      prophylactic heparinization were randomized to groups MEST and control. MEST
      patients received 30-minute MEST sessions twice daily for 7 to 14 days. Venous
      flow velocity and venous diameter were measured by duplex venous scan. Venography
      or, if not available, duplex-was used to evaluate the presence of proximal and
      peripheral DVT between days 7 and 15. RESULTS: After exclusions, 26 MEST and 21
      control patients completed the study and received outcome evaluation by
      venography (25) or duplex (22). Three patients in each group developed proximal
      DVT (11.5% vs 14%, P = .79), and an additional 4 (15%) MEST group and 3 (14%)
      control group patients developed peripheral DVT ( P = .96). There was no
      difference in venous flow velocity or venous diameter between the groups.
      CONCLUSIONS: MEST was not effective in decreasing DVT rates in major trauma
      patients.

PMID- 15855920
TI  - Early and late complications after pancreatic necrosectomy.
AB  - BACKGROUND: Surgery for pancreatic necrosis is associated with a high morbidity
      and mortality. The aim of this study was to review the incidence of early and
      late complications after pancreatic necrosectomy in a large contemporary series
      of patients. METHODS: The clinical outcomes of 88 patients who underwent
      pancreatic necrosectomy between 1997 and 2003 were reviewed. RESULTS: The median
      age was 55.5 (range, 18-85) years, 54 (61%) were males, 68 (77%) had primary
      pancreatic infection, 71 (81%) had >50% necrosis, and the median admission Acute
      Physiology and Chronic Health Evaluation score was 9 (range, 1-21). Median time
      to surgery was 31 (range, 1-161) days; 47 patients underwent minimally invasive
      necrosectomy and 41 open necrosectomy; 81 (92%) of patients had complications
      postoperatively, and 25 (28%) died. Multiorgan failure (odds ratio = 3.4, P =
      .05) and hemorrhage (odds ratio = 6.1, P = .03) were the only independent
      predictors of mortality. During a median follow-up of 28.9 months, 39 (62%) of 63
      surviving patients had one or more late complications: biliary stricture in 4
      (6%), pseudocyst in 5 (8%), pancreatic fistula in 8 (13%), gastrointestinal
      fistula in 1 (2%), delayed collections in 3 (5%), and incisional hernia in 1
      (2%); intervention was required in 10 (16%) patients. Sixteen (25%) of 63
      surviving patients developed exocrine insufficiency, and 19 (33%) of 58 without
      prior diabetes mellitus developed endocrine insufficiency. CONCLUSIONS: Almost
      all patients undergoing necrosectomy developed significant early or late
      complications or both. Multiorgan failure and postoperative hemorrhage were
      independent predictors of mortality. Long-term follow-up was important because
      62% developed complications, and 16% of those with complications required
      surgical or endoscopic intervention.

PMID- 15855921
TI  - Benign hilar biliary strictures stented with metallic stents can be resected by
      using an oncologic approach.
AB  - BACKGROUND: Biliary metallic stents (MS) are being used increasingly to treat
      patients with malignant bile duct strictures. In patients with benign strictures,
      MS are contraindicated because these stents are considered unremovable. The aim
      of this study was to report the operative treatment of patients with benign
      biliary strictures at the hepatic confluence stented with MS. METHODS: Five
      patients with a benign hilar stenosis stented with MS underwent liver resection
      with biliodigestive anastomoses. The operations were designed to remove all MS by
      a combined biliary and hepatic resection. RESULTS: After preoperative portal vein
      embolization in 2 patients and percutaneous biliary drainage in 2 others, all
      underwent a major hepatectomy with resection of the biliary confluence and a
      biliodigestive anastomosis. One patient also underwent resection of the portal
      vein bifurcation that could not be freed from the bile duct wall. Four patients
      experienced postoperative complications. With a mean follow-up of 37 months
      (range, 31-47 months), all patients have remained symptom-free. CONCLUSIONS:
      Operative treatment of benign hilar strictures in patients with MS is possible if
      they are managed similarly as patients with hilar malignancies. This demanding
      procedure should be considered an alternative to liver transplantation for benign
      strictures treated with MS, but the procedure requires expertise in advanced
      hepatic resections.

PMID- 15855922
TI  - Evaluation of prognostic significance in extracapsular spread of lymph node
      metastasis in patients with gastric cancer.
AB  - BACKGROUND: Extracapsular spread of lymph node metastasis has been shown as a
      negative prognostic factor in cancers of several other organs. This study was
      performed to clarify the prognostic significance of extracapsular spread in
      patients receiving curative resection for gastric cancer. METHODS: Extracapsular
      spread was defined as infiltration of cancer cells beyond the capsule of the
      metastatic lymph node. Four hundred and two patients who underwent curative
      gastrectomy were evaluated. Eight potential prognostic factors, including the
      International Union Against Cancer (Union International Contra la Cancrum;
      [UICC]) N stage and nodal status classified by the presence of lymph node
      metastasis or extracapsular spread, were examined. RESULTS: Three survival curves
      grouped by nodal status differed significantly, and prognosis of patients with
      extracapsular spread was significantly worse than for the other groups. Both UICC
      N stage ( P < .001) and nodal status ( P < .001) were significant prognostic
      factors by multivariate analysis. UICC N stages were subcategorized by nodal
      status, and survival was shown to be significantly worse in patients with
      extracapsular spread in the UICC N1 group ( P = .04). CONCLUSIONS: Extracapsular
      spread was a significant negative prognostic indicator on multivariate analysis,
      and may be useful in combination with UICC N stage. Extracapsular spread was
      regarded as an important indicator to refine the nodal staging system in gastric
      cancer.

PMID- 15855924
TI  - Introducing new technology into the operating room: measuring the impact on job
      performance and satisfaction.
AB  - BACKGROUND: The Massachusetts General Hospital (MGH) Operating Room of the Future
      (ORF) project is a test site for evaluating new surgical technologies and
      processes. Here we evaluate the effect on staff satisfaction and burnout of
      introducing a set of new technologies. METHODS: Staff satisfaction and burnout
      were measured via sequential surveys based on the Maslach Burnout Inventory
      during the introduction of a new technology system. Functional behavior of the OR
      was measured in terms of flow time (time to transit the OR) and wait time (time
      to access the OR). These data were gathered using time-motion analysis methods.
      RESULTS: Significant functional improvements were found in the ORF (more than 35%
      reduction in flow time and wait time, P < .05). During the same period, more
      exposure to the ORF resulted in greater sense of personal accomplishment among
      surgeons, a worse sense of personal accomplishment among nurses, more emotional
      exhaustion among surgeons, and less emotional exhaustion among nurses. However,
      the responses for emotional exhaustion were reversed the greater the time from
      exposure to the ORF. Staff with 6 to 10 years' experience were at highest risk
      for burnout across all categories. General surgeons experienced more emotional
      exhaustion than other physicians. CONCLUSIONS: Tracking the response of all users
      and identifying groups at high risk for burnout when exposed to new systems
      should be a central part of any new technology project.

PMID- 15855925
TI  - Oncolytic adenoviral therapy in gallbladder carcinoma.
AB  - BACKGROUND: Oncolytic adenoviral therapy is a promising new approach for cancer
      treatment. The aim of this study was to improve the conditionally replicative
      adenoviruses (CRAds) for gallbladder cancer therapy by modifying the fiber-knob
      region for infectivity enhancement and by incorporating tumor-specific promoters
      (TSPs) for enhanced specificity. METHODS: For promoter-controlled replication, in
      vitro efficacy of eight TSPs was investigated in two gallbladder cancer cell
      lines (NOZ and OCUG-1). Infectivity enhancement was analyzed by two different
      fiber modifications: Arg-Gly-Asp (RGD) incorporation into the HI loop (RGD
      modification) and a chimeric construct with a serotype 5 shaft and a serotype 3
      knob (5/3 fiber modification). Comparisons were made by infectivity analysis and
      cytotoxicity assays in vitro, followed by tumor suppressive effects tested in
      vivo. RESULTS: Among TSPs, highest potency was exhibited by the cyclooxygenase-2
      (COX-2), Midkine, and vascular endothelial growth factor promoters in both cell
      lines tested. Fiber chimera (Ad5/3Luc1) conferred significant enhancement of Ad
      infectivity in comparison with unmodified and RGD-modified vectors. COX-2 CRAds
      demonstrated selective cytocidal effect in gallbladder cancer cells in vitro. COX
      2 promoter-based Ad5/3 CRAds showed significantly enhanced tumor-suppressive
      effect compared with nonreplicative and RGD-modified CRAd vectors in vivo.
      CONCLUSIONS: The 5/3 fiber-modified, COX-2 promoter-driven CRAds may prove to be
      a new agent for the treatment of gallbladder carcinoma.

PMID- 15855926
TI  - Reduced tumor vessel density and high expression of glucose transporter 1 suggest
      tumor hypoxia of squamous cell carcinoma of the esophagus surviving after
      radiotherapy.
AB  - BACKGROUND: Squamous cell carcinoma of the esophagus (ESCC) is radiosensitive;
      however, surgeons frequently encounter ESCC that survives radiotherapy to grow
      more rapidly and invasively. This alteration of tumor behavior may result from
      tumor hypoxia induced by radiotherapy. METHODS: Forty-four patients with advanced
      (T3 and T4) ESCC, who underwent radiotherapy before operation, either with 40 Gy
      for preoperative treatment or 60 Gy or more for radical treatment, and 44
      patients without preoperative therapy were subjected to retrospective
      immunohistochemical study. CD34 for tumor vessels, glucose transporter 1 (GLUT1)
      which was induced by hypoxia, MIB-1 for proliferating activity, and p53 were
      stained for surgical samples from ESCC patients. Tumor tissue at the invading
      front was the focus of evaluation. Macroscopic morphologic differences of ESCC
      were also evaluated. RESULTS: Loss of esophageal wall thickness and deep
      ulceration were morphologic characteristics of ESCC after radiotherapy. Tumor
      vessel density was reduced and GLUT1 expression was greater in the ESCC after
      radiotherapy than in those without treatment. Tumor vessel density was similar
      for both preoperative and radical radiotherapy samples, while GLUT1 expression
      tended to be greater in the latter than in the former. The expression of MIB-1
      and p53 did not show any significant difference between ESCC with or without
      radiotherapy. CONCLUSIONS: Reduced vessel density and increased GLUT1 expression
      suggested tumor hypoxia for ESCC occurred after radiotherapy. Tumor hypoxia would
      induce ulcerative and invasive growth, which is a great obstacle to clinical
      treatment of residual or relapse ESCC after radiotherapy.

PMID- 15855927
TI  - Macrophage ablation attenuates adenoviral vector-induced pancreatitis.
AB  - BACKGROUND: The objective of these studies is to determine the effects of
      macrophage ablation on the course of acute viral pancreatitis. Macrophages
      secrete proinflammatory cytokines triggering local pancreatic and systemic
      inflammation in the acute phase of virus-induced pancreatitis. We hypothesized
      that ablation of macrophages should attenuate the host inflammatory response in a
      mouse model of adenovirus-induced pancreatitis. METHODS: Liposome-encapsulated
      dichloromethylene-diphosphonate, a macrophage-depleting agent, was used before
      direct pancreatic injection of a recombinant adenovirus expressing a marker gene
      in C57Bl/6 and IL-6 knockout (KO) mice. RESULTS: C57Bl/6 mice depleted of
      macrophages had diminished pancreatic inflammation in the first 24 hours after
      vector administration. IL-6 KO mice depleted of macrophages had more severe
      inflammation than similarly treated C57Bl/6 mice. C57Bl/6 mice depleted of
      macrophages, and IL-6 KO mice had prolonged transgene expression and diminished
      cytotoxic T lymphocyte responses to adenoviral vector. Mortality was highest in
      IL-6 KO mice depleted of macrophages. Depletion of macrophages also prevented
      detectable serum IL-6, IL-10, or IL-12 levels in C57Bl/6 mice. CONCLUSIONS: The
      data suggest that macrophages play a role in the acute inflammatory response to
      viral vector-induced pancreatitis and that IL-6 may be protective. Understanding
      of the mechanisms that initiate the host immune cascade will allow more effective
      use of adenoviral vector-based pancreatic gene delivery.

PMID- 15855928
TI  - Circulating tumor cells detected by reverse transcription-polymerase chain
      reaction for carcinoembryonic antigen mRNA: distinguishing follicular thyroid
      carcinoma from adenoma.
AB  - BACKGROUND: We prospectively tested whether circulating tumor cells could be
      detected in peripheral blood of patients with thyroid tumors by a reverse
      transcription-polymerase chain reaction (RT-PCR) to detect carcinoembryonic
      antigen (CEA) messenger RNA (mRNA). METHODS: We assayed for CEA mRNA by RT-PCR in
      peripheral blood sampled before and 2 to 3 weeks after curative surgery for
      thyroid tumors in 121 patients. Blood samples from 7 patients with chronic
      thyroiditis and 7 healthy subjects served as controls. RESULTS: No control
      samples were positive for CEA mRNA by RT-PCR. Of 121 preoperative samples from
      patients with thyroid tumor, 6 were positive (5.0%). Preoperative frequencies of
      CEA mRNA positivity in benign tumor, papillary carcinoma, follicular variant
      papillary carcinoma, minimally invasive follicular carcinoma, and widely invasive
      follicular carcinoma were 0%, 0%, 0%, 44.4% (4/9), and 50.0% (2/4), respectively.
      Among positive patients only one, who had widely invasive follicular carcinoma,
      remained positive after surgery. CONCLUSIONS: RT-PCR detection of tumor cells in
      preoperative blood often can distinguish malignant from benign follicular thyroid
      tumors.

PMID- 15855930
TI  - Carbon dioxide pneumoperitoneum-mediated attenuation of the inflammatory response
      is independent of systemic acidosis.
AB  - BACKGROUND: The purpose of this study was to determine if systemic acidosis
      induced by peritoneal absorption of carbon dioxide (CO2 ) during laparoscopy
      plays a role in CO2 pneumoperitoneum-mediated attenuation of the acute phase
      inflammatory response associated with perioperative sepsis. The influence of
      hepatic polymorphonuclear (PMN) leukocyte infiltration on this phenomenon was
      also investigated. METHODS: Forty-five rats were randomized into 5 groups:
      anesthesia control, open cecal ligation and puncture (OCLP), laparoscopic cecal
      ligation and puncture using helium for insufflation (He LCLP), LCLP using CO2
      with continued spontaneous ventilation (LCLP-SV), and LCLP using CO2 with
      intubation and positive pressure ventilation (LCLP-PPV). RESULTS: After 30
      minutes, arterial blood gas parameters remained normal in control, OCLP rats, and
      He LCLP rats, while CO2 LCLP-SV rats developed significant hypercarbic acidosis.
      This acidosis was corrected in CO2 LCLP-PPV rats ( P < .0001 vs CO2 LCLP-SV for
      both). Expression of the rat acute phase gene alpha 2 -macroglobulin was greater
      after OCLP and He LCLP than after either CO2 LCLP-SV or CO2 LCLP-PPV ( P < .0001
      vs either CO2 OCLP-SV for both). However, levels of alpha 2 -macroglobulin were
      not significantly different between the acidotic (LCLP-SV) and normocarbic (LCLP
      PPV) CO2 groups. Infiltration of the hepatic parenchyma by PMNs did not differ
      significantly between groups. CONCLUSIONS: CO2 insufflation-induced systemic
      acidosis is not responsible for the reduction in the acute phase inflammatory
      response observed in laparoscopic animal models of sepsis. Hepatic PMN
      infiltration also does not appear to mediate this effect.

PMID- 15855931
TI  - A new surgical technique for treatment of preauricular sinus.
AB  - BACKGROUND: The objectives of this paper are to describe the shortcomings of
      current techniques for treatment of preauricular sinus (PAS) and to introduce a
      new surgical technique. PAS is a common congenital abnormality. Usually these
      lesions are asymptomatic. However, some patients complain of discharge and/or
      (recurrent) infections, and require excision. Surgical treatment of PAS is
      characterized by high recurrence rates. This paper describes a single
      institution's experience with the operative management of PAS and introduces a
      new technique. METHODS: Data on PAS procedures were collected from a
      retrospective review of patients' charts and interviews by questionnaire of all
      patients treated operatively for PAS in the Leiden University Medical Centre from
      1984 to 2003. RESULTS: Thirty-nine patients (21 male, 18 female) with PAS
      underwent 40 procedures for PAS. These procedures included 17 classic operations
      (in 16 patients) and the "inside-out technique" in 23 patients. In the patient
      group treated "classically," 2 patients developed a recurrence; one underwent
      successful reoperation; the other patient has been lost to follow-up. Another
      patient developed wound breakdown postoperatively, resulting in an ugly scar. Two
      patients had postoperative infections requiring treatment. Neither recurrences
      nor complications requiring treatment occurred in the group who underwent the
      inside-out technique. CONCLUSIONS: The inside-out technique provides an easy
      solution for patients with PAS. However, further study on a larger patient group
      is necessary.

PMID- 15855932
TI  - Inflammation in surgical wound healing: friend or foe?

PMID- 15855933
TI  - The familial medullary thyroid carcinoma-associated RET E768D mutation in a
      multiple endocrine neoplasia type 2A case.

PMID- 15855934
TI  - Successful complete resection of biliary cystadenocarcinoma after percutaneous
      transhepatic portal embolization.

PMID- 15855935
TI  - Multilocular peritoneal inclusion cyst.

PMID- 15855936
TI  - The giant and the gentleman, or I bet he kicks the dog!

PMID- 15855937
TI  - Re: "The role of median sternotomy in resections for large hepatocellular
      carcinomas".

PMID- 15855939
TI  - Effect of increased ICU capacity on emergency department length of stay and
      ambulance diversion.
AB  - STUDY OBJECTIVE: Lack of inpatient bed availability has been identified as a
      major contributor to emergency department (ED) crowding. Our objective is to
      determine the changes in ED length of stay and ambulance diversion occurring in
      an urban, academic medical center after an increase in adult ICU beds. METHODS:
      This was a secondary analysis of 2 years of hospital administrative data,
      capitalizing on a natural experiment in which the number of adult ICU beds in the
      study hospital increased from 47 to 67 (total beds 411 to 431). We analyzed
      changes in ED length of stay for adults admitted to ICU, telemetry beds, and ward
      beds and adults discharged home. We also analyzed changes in hours per day spent
      on 3 types of ambulance diversion: complete diversion (all ambulances), critical
      care diversion (ambulances carrying patients requiring ICU beds), and diversion
      of ambulances carrying trauma patients. RESULTS: The average hours per day on
      complete ambulance diversion decreased from 3.8 hours to 1.4 hours (66%
      decrease). Critical care and trauma diversion showed similar decreases. Average
      ED length of stay for patients admitted to the ICU decreased by 25 minutes (257
      to 232 minutes). Average ED length of stay did not significantly decrease for
      other admitted patients and increased for discharged patients. CONCLUSION: The
      most notable change after ICU expansion was a decrease in time spent on ambulance
      diversion. Increasing ICU beds appears to have shortened ED length of stay for
      ICU patients but has less effect on other admitted patients and apparently no
      effect on patients discharged home.

PMID- 15855940
TI  - An agenda for reducing emergency department crowding.

PMID- 15855941
TI  - Images in emergency medicine. Le Fort II fracture.

PMID- 15855942
TI  - The cost of an emergency department visit and its relationship to emergency
      department volume.
AB  - STUDY OBJECTIVE: This article addresses 2 questions: (1) to what extent do
      emergency departments (EDs) exhibit economies of scale; and (2) to what extent do
      publicly available accounting data understate the marginal cost of an outpatient
      ED visit? Understanding the appropriate role for EDs in the overall health care
      system is crucially dependent on answers to these questions. The literature on
      these issues is sparse and somewhat dated and fails to differentiate between
      trauma and nontrauma hospitals. We believe a careful review of these questions is
      necessary because several changes (greater managed care penetration, increased
      price competition, cost of compliance with Emergency Medical Treatment and Active
      Labor Act regulations, and so on) may have significantly altered ED economics in
      recent years. METHODS: We use a 2-pronged approach, 1 based on descriptive
      analyses of publicly available accounting data and 1 based on statistical cost
      models estimated from a 9-year panel of hospital data, to address the above
      mentioned questions. RESULTS: Neither the descriptive analyses nor the
      statistical models support the existence of significant scale economies.
      Furthermore, the marginal cost of outpatient ED visits, even without the
      emergency physician component, appear quite high--in 1998 dollars, US295 dollars
      and US412 dollars for nontrauma and trauma EDs, respectively. These statistical
      estimates exceed the accounting estimates of per-visit costs by a factor of
      roughly 2. CONCLUSION: Our findings suggest that the marginal cost of an
      outpatient ED visit is higher than is generally believed. Hospitals thus need to
      carefully review how EDs fit within their overall operations and cost structure
      and may need to pay special attention to policies and procedures that guide the
      delivery of nonurgent care through the ED.

PMID- 15855943
TI  - Calculating the cost of emergency care.

PMID- 15855944
TI  - The costs of providing nonurgent care in emergency departments.

PMID- 15855945
TI  - Nonurgent care in the emergency department: can we save by shifting the site of
      care?

PMID- 15855946
TI  - The effectiveness of out-of-hospital use of continuous end-tidal carbon dioxide
      monitoring on the rate of unrecognized misplaced intubation within a regional
      emergency medical services system.
AB  - STUDY OBJECTIVE: We evaluate the association between out-of-hospital use of
      continuous end-tidal carbon dioxide (ETCO2) monitoring and unrecognized misplaced
      intubations within a regional emergency medical services (EMS) system. METHODS:
      This was a prospective, observational study, conducted during a 10-month period,
      on all patients arriving at a regional Level I trauma center emergency department
      who underwent out-of-hospital endotracheal intubation. The regional EMS system
      that serves the trauma service area is composed of multiple countywide systems
      containing numerous EMS agencies. Some of the EMS agencies had independently
      implemented continuous ETCO2 monitoring before the start of the study. The main
      outcome measure was the unrecognized misplaced intubation rate with and without
      use of continuous ETCO2 monitoring. RESULTS: Two hundred forty-eight patients
      received out-of-hospital airway management, of whom 153 received intubation. Of
      the 153 patients, 93 (61%) had continuous ETCO2 monitoring, and 60 (39%) did not.
      Forty-nine (32%) were medical patients, 104 (68%) were trauma patients, and 51
      (33%) were in cardiac arrest. The overall incidence of unrecognized misplaced
      intubations was 9%. The rate of unrecognized misplaced intubations in the group
      for whom continuous ETCO2 monitoring was used was zero, and the rate in the group
      for whom continuous ETCO2 monitoring was not used was 23.3% (95% confidence
      interval 13.4% to 36.0%). CONCLUSION: No unrecognized misplaced intubations were
      found in patients for whom paramedics used continuous ETCO2 monitoring. Failure
      to use continuous ETCO2 monitoring was associated with a 23% unrecognized
      misplaced intubation rate.

PMID- 15855947
TI  - Cardiac Arrest Resuscitation Evaluation in Los Angeles: CARE-LA.
AB  - STUDY OBJECTIVE: We determine survival for out-of-hospital cardiac arrests in Los
      Angeles using the Utstein method and compare these data with that reported for
      other urban and suburban areas. METHODS: This was a prospective observational
      cohort study of adult patients in Los Angeles presenting with nontraumatic, out
      of-hospital cardiac arrest and with attempted out-of-hospital resuscitative
      efforts between July 1, 2000, and July 1, 2001. Entry criteria, time intervals,
      and nodal events conformed to Utstein template recommendations. The single target
      endpoint was neurologically intact survival at hospital discharge. RESULTS: Of
      2,021 consecutive cardiac arrest patients on whom resuscitation was attempted,
      1,700 (84%) met entry criteria as a primary cardiac event. Overall,
      neurologically intact survival was 1.4% (99% confidence interval [CI] 0.8% to
      2.4%) Three patients were lost to follow-up. Survival from bystander-witnessed
      ventricular fibrillation was 6.1% (99% CI 3.3% to 11.0%). Absolute survival
      differences from witnessed ventricular fibrillation was higher but not
      statistically different than that from Chicago (-3%; 99% CI -8% to 2%) and New
      York City (-2%; 99% CI -6% to 3%). The rate of bystander cardiopulmonary
      resuscitation (CPR) for our population was 28%, for which the overall survival
      rate was 2.1%. The survival rate for patients with witnessed arrests and
      bystander CPR was 3.2%. Among patients with no bystander CPR, the survival rate
      was 1.0%. CONCLUSION: Survival from out-of-hospital cardiac arrest in Los Angeles
      was low but similar to that reported for New York and Chicago. This low survival
      rate may be due to population density, low bystander CPR rates, and traffic
      congestion delaying emergency response.

PMID- 15855948
TI  - Use of ultrasonography to identify infants for whom urinary catheterization will
      be unsuccessful because of insufficient urine volume: validation of the urinary
      bladder index.
AB  - STUDY OBJECTIVE: Frequently, attempts to obtain catheter urine samples from
      infants are unsuccessful because of an empty bladder, with urinary
      catheterization failure rates reported up to 16%. We seek to validate a
      sonographic urinary bladder index that will identify patients for whom
      catheterization will be unsuccessful. METHODS: We conducted a prospective,
      blinded, observational study enrolling a convenience sample of children younger
      than 2 years and undergoing urinary catheterization in an urban pediatric
      emergency department. Failure was defined as a catheterization result of less
      than 2 mL of urine. Urinary bladder index, a concept we created, is defined as
      the product of anteroposterior and transverse diameters, expressed in centimeters
      squared. Sensitivity and specificity were calculated with 95% confidence
      intervals (CIs). RESULTS: Forty-four patients were enrolled, with a median age of
      8 months (range 0.5 to 24 months) and median weight of 7.8 kg (range 1.7 to 17.7
      kg). Four children urinated during the procedure and were excluded. Thirty-five
      had urinary bladder index greater than 2.4 cm2 (range 2.5 to 15.5 cm2 ). All were
      successfully catheterized. Four children had urinary bladder index less than 2.4
      cm2 (range 0 to 1.2 cm 2 ). No adequate samples were obtained from those
      children. The bladder was not visualized at all in 1 child who was successfully
      catheterized. Sensitivity of the urinary bladder index to identify failure to
      obtain 2 mL of urine was 100% (4 of 4; 95% CI 40% to 100%), specificity was 97%
      (35 of 36; 95% CI 85% to 100%). CONCLUSION: A urinary bladder index less than 2.4
      cm2 appears to identify infants for whom urinary catheterization will be
      unsuccessful because of insufficient urine volume. Ultrasonographic evaluation
      with urinary bladder index measurement before catheterization may eliminate the
      incidence of failed procedures.

PMID- 15855949
TI  - The new clinical practice guidelines for acute otitis media: an editorial.

PMID- 15855950
TI  - Ominous findings in toddlers with increasing abdominal girth: two unusual cases
      and a review of the clinical evaluation.
AB  - A preverbal toddler who presents with a distended abdomen can pose a difficult
      clinical problem. The differential diagnosis is extremely broad and consists of
      etiologies ranging from the benign to the life threatening. In this case report,
      we present 2 unusual life-threatening cases of abdominal distention in well
      appearing toddlers and a review of the clinical evaluation for the emergency
      practitioner.

PMID- 15855951
TI  - Serum lactate as a predictor of mortality in emergency department patients with
      infection.
AB  - STUDY OBJECTIVE: Little is known about risk-stratification biomarkers in
      emergency department (ED) patients with suspected infection, and lactate is a
      biologically plausible candidate. We determine whether a serum venous lactate is
      associated with an increased risk of death in ED patients with infection.
      METHODS: This was a prospective cohort study in an urban, academic medical center
      with 50,000 annual ED visits. A total of 1,278 consecutive patient visits met
      enrollment criteria between July 24, 2003, and March 24, 2004, and all patients
      were enrolled. Inclusion criteria were age 18 years or older, serum lactate level
      obtained, and admission to the hospital with an infection-related diagnosis. The
      main outcome measure was all-cause 28-day inhospital mortality and death within 3
      days of presentation. RESULTS: Among 1,278 patient visits, there were 105 (8.2%)
      deaths during hospitalization, with 55 (4.3%) of 1,278 deaths occurring in the
      first 3 days. Mortality rates increased as lactate increased: 43 (4.9%) of 877 of
      patients with a lactate level between 0 and 2.5 mmol/L died, 24 (9.0%) of 267
      patients with a lactate level between 2.5 and 4.0 mmol/L died, and 38 (28.4%) of
      134 patients with a lactate level greater than or equal to 4.0 mmol/L died.
      Lactate level greater than or equal to 4.0 mmol/L was 36% (95% confidence
      interval [CI] 27% to 45%) sensitive and 92% (95% CI 90% to 93%) specific for any
      death; it was 55% (95% CI 41% to 68%) sensitive and 91% (95% CI 90% to 93%)
      specific for death within 3 days. CONCLUSION: In this cohort of ED patients with
      signs and symptoms suggestive of infection, our results support serum venous
      lactate level as a promising risk-stratification tool. Multicenter validation, as
      well as comparison of the lactate level with clinical predictors, needs to be
      done before widespread implementation.

PMID- 15855952
TI  - Update on emerging infections: news from the Centers for Disease Control and
      Prevention. Outbreak of cyclosporiasis associated with snow peas--Pennsylvania,
      2004.

PMID- 15855954
TI  - Report of the Task Force on Residency Training Information (2004-2005), American
      Board of Emergency Medicine.
AB  - The American Board of Emergency Medicine gathers extensive background information
      on emergency medicine residency training programs and the residents training in
      those programs. We present the eighth annual report on the status of US emergency
      medicine residency programs.

PMID- 15855955
TI  - Are blood cultures necessary in adults with cellulitis?

PMID- 15855956
TI  - Arterial blood gas analysis: are its values needed for the management of diabetic
      ketoacidosis?

PMID- 15855959
TI  - Images in emergency medicine. Petechiae and purpura associated with
      meningococcemia.

PMID- 15855960
TI  - Munchausen syndrome: an endless search for self, managed by house arrest and
      mandated treatment.

PMID- 15855961
TI  - The acetaminophen toxicity equations: "solutions" for acetaminophen toxicity
      based on the Rumack-Matthew nomogram.

PMID- 15855962
TI  - Clinical policy on pediatric procedural sedation.

PMID- 15855963
TI  - Recommendation of the minimal volume technique to avoid tongue engorgement with
      prolonged use of the esophageal-tracheal combitube.

PMID- 15855966
TI  - Endoscopic full-thickness plication for the treatment of GERD: 12-month follow-up
      for the North American open-label trial.
AB  - BACKGROUND: The aim of this study was to assess the intermediate-term (12-month)
      safety and efficacy of endoscopic full-thickness plication in patients with
      symptomatic GERD. METHODS: Sixty-four patients with chronic heartburn that
      required maintenance antisecretory therapy received a single, endoscopically
      placed, full-thickness plication in the gastric cardia 1 cm distal to the
      gastroesophageal junction. At baseline and 12 months after plication, patients
      completed the GERD Health Related Quality of Life questionnaire, Gastrointestinal
      Symptom Rating Scale, and SF-36 Health Survey, as well as a medication use diary.
      Ambulatory 24-hour pH monitoring and esophageal manometry were obtained at
      baseline and 3 months after plication. At 6 months after plication, the 24-hour
      pH study was repeated. RESULTS: Of the 57 patients who completed the 12-month
      follow-up, 40 (70%) were no longer taking a proton pump inhibitor. Median GERD
      Health Related Quality of Life scores were improved compared with baseline while
      taking medication (19.0 vs. 5.0; p < 0.0001) and while not taking medication
      (13.0 vs. 5.0; p < 0.002). At 6 months after the procedure, an improvement in
      distal esophageal acid exposure was demonstrated in 40 of 51 patients (80%), with
      a decrease of 39% in the median percentage of time the pH was less than 4 (p <
      0.0001). Normal pH scores were observed in 30% of patients. All procedure-related
      adverse events occurred acutely, as previously reported, and no new adverse event
      was observed during extended follow-up. CONCLUSIONS: Full-thickness plication at
      the gastroesophageal junction is an effective endoscopic procedure for treatment
      of patients with symptoms caused by GERD. It reduces reflux symptoms and
      antisecretory medication use over at least a 1-year period.

PMID- 15855967
TI  - Enteryx implantation for GERD: expanded multicenter trial results and interim
      postapproval follow-up to 24 months.
AB  - BACKGROUND: Enteryx implantation in the esophagus is an alternative therapy for
      patients with proton pump inhibitor (PPI) dependent GERD. Although this treatment
      resulted in highly significant improvement at 6 and 12 months, longer follow-up
      is needed to more fully assess the durability of these positive effects. METHODS:
      An open-label, international clinical trial was conducted in 144 PPI-dependent
      patients with GERD with follow-up at 6 and 12 months. In addition, the durability
      and the safety of the treatment were assessed for 24 months in 64 patients
      enrolled in a postapproval study. The primary study outcome measure was usage of
      PPI. Secondary outcomes in the multicenter trial were GERD health-related quality
      of life (GERD-HRQL) symptom score and esophageal acid exposure. RESULTS: At 12
      months, PPI use was reduced > or =50% in 84%: 95% confidence interval (CI) [76%,
      90%] and was eliminated in 73%: 95% CI[64%, 81%] of evaluable patients (intent-to
      treat analysis 78%: 95% CI[70%, 84%] and 68%: 95% CI[60%, 76%], respectively). A
      GERD-HRQL < or =11 was attained in 78%: 95% CI[69%, 85%] of evaluable patients.
      Esophageal acid exposure (total time pH <4) was reduced by 31%: 95% CI[17%, 43%].
      At 24 months, a > or =50% or greater reduction in PPI use was achieved in 72%:
      95% CI[59%, 82%] and PPI use was eliminated in 67%: 95% CI[54%, 78%] of patients.
      CONCLUSIONS: This investigation provides evidence for sustained effectiveness and
      safety of implantation of Enteryx in the esophagus in PPI-dependent patients with
      GERD.

PMID- 15855968
TI  - Long-term outcomes of endoluminal gastroplication: a U.S. multicenter trial.
AB  - BACKGROUND: Endoluminal gastroplication has shown promise for the treatment of
      GERD in short-term studies. Until now, long-term outcome data have been lacking.
      METHODS: A prospective, multicenter trial enrolled 85 patients with GERD to be
      treated with endoluminal gastroplication. Inclusion criteria were 3 or more
      heartburn or regurgitation episodes per week, >4.2% time in 24 hours with
      esophageal pH < 4, and dependency on antisecretory medications. Exclusion
      criteria were the presence of varices, achalasia, aperistalsis, or previous
      gastric resection. Patients underwent manometry, 24-hour pH monitoring, and
      symptom severity scoring before and after the procedure. Patient diaries were
      used to assess medication use and to estimate annual medication cost. RESULTS: At
      1- and 2-year follow-up, patients had significant reductions in median heartburn
      symptom scores (72 at baseline [interquartile range (IQR) 90-48] vs. 4 at 12
      months [IQR 43-0] and 16 at 24 months [IQR 53-3.5]; p < 0.0001 vs. baseline) and
      median regurgitation symptoms (2 at baseline [IQR 3-1] vs. 0 at 12 months (IQR 1
      0) and 1 at 24 months [IQR 1-0]; p < 0.0001 vs. baseline). Of all patients, 59%
      and 52% showed heartburn symptom resolution at 12 and 24 months, respectively ( p
      < 0.0001 vs. baseline). Also, 83% and 77% had regurgitation symptom resolution at
      12 and 24 months, respectively (p < 0.0001 vs. baseline). Proton pump inhibitor
      use also was significantly reduced at 12 and 24 months after the procedure. At 2
      year follow-up, median annualized medication costs were reduced by 88% (1381 US
      dollars) (p < 0.0001). Endoluminal gastroplication significantly reduced the
      duration and the number of episodes of esophageal acid exposure (p < 0.0001 vs.
      baseline). Only 7 patients experienced adverse events. CONCLUSIONS: Endoscopic
      gastroplication is safe and effective, and is associated with symptom reductions
      in patients with GERD for at least 24 months.

PMID- 15855969
TI  - Endotherapy for GERD: angels and demons.

PMID- 15855970
TI  - A randomized crossover study comparing light-induced fluorescence endoscopy with
      standard videoendoscopy for the detection of early neoplasia in Barrett's
      esophagus.
AB  - BACKGROUND: Light-induced fluorescence endoscopy (LIFE) may improve the detection
      of high-grade dysplasia (HGD) and early stage cancer (EC) in Barrett's esophagus
      (BE). The aim of this study was to compare LIFE with standard endoscopy (SE) in a
      randomized crossover study. METHODS: Fifty patients with BE underwent SE and LIFE
      in a randomized sequence (4 to 6-week interval between procedures). The two
      procedures were performed by two different endoscopists who were blinded to the
      findings of the other examination. Targeted biopsy specimens were taken from
      detected lesions, followed by random biopsy specimens with a 2-cm interval, 4
      quadrant protocol. Biopsy specimens were routinely evaluated and subsequently
      reviewed by a single, blinded expert GI pathologist. RESULTS: Targeted biopsy
      specimens had a sensitivity for the diagnosis of HGD/EC of 62% (8/13) for both
      techniques. The overall sensitivity (all biopsy specimens) was 85% for SE and 69%
      for LIFE (p = 0.69). All targeted biopsy specimens had a positive predictive
      value (PPV) for HGD/EC of 41% for SE and 28% for LIFE (p = 0.40);
      autofluorescence-targeted biopsy specimens had a PPV of 13%. False-positive
      lesions had a significantly higher rate of acute inflammation than random biopsy
      specimens. CONCLUSIONS: In this study, LIFE did not improve the detection of HGD
      or EC in patients with BE compared with SE.

PMID- 15855971
TI  - Endoscopic video autofluorescence imaging may improve the detection of early
      neoplasia in patients with Barrett's esophagus.
AB  - BACKGROUND: The aim of this study was to investigate the feasibility of detecting
      high-grade dysplasia (HGD) and early cancer (EC) in Barrett's esophagus (BE) with
      a prototype video autofluorescence endoscope. METHODS: Sixty patients with BE
      were evaluated with a prototype, high-resolution videoendoscope that has separate
      charge-coupled devices for white light endoscopy (WLE) and autofluorescence
      imaging (AFI). Nondysplastic BE appears green on AFI, whereas potentially
      neoplastic areas appear blue/violet. The BE was first screened with WLE for
      visible abnormalities and then was examined by AFI to detect additional lesions.
      Lesions that raised a suspicion of neoplasia and control areas that were normal
      on AFI were sampled for histopathologic assessment. Finally, random 4-quadrant
      biopsy specimens were obtained at 2-cm intervals. RESULTS: A diagnosis of HGD/EC
      was made in 22 patients; one patient had no visible abnormality, and 21 had
      endoscopically detectable areas with HGD/EC. In 6 of the latter 21 patients, the
      HGD/EC was detected with AFI alone; in another patient, HGD/EC was detected with
      AFI and random biopsies. In 14 patients, HGD/EC was detected with both WLE and
      AFI; in 3 of these 14 patients, additional lesions containing HGD/EC were
      detected by AFI alone. CONCLUSIONS: The results of this study suggest that video
      AFI may improve the detection of HGD/EC in patients with BE.

PMID- 15855972
TI  - Autofluorescence imaging: have we finally seen the light?

PMID- 15855973
TI  - EUS-guided FNA of pancreatic metastases: a multicenter experience.
AB  - BACKGROUND: Metastatic lesions of the pancreas are a rare but important cause of
      focal pancreatic lesions. The purpose of this study is to describe the EUS
      features, cytologic diagnoses, and clinical impact of a cohort of patients with
      pancreatic metastases diagnosed by EUS-guided FNA (EUS-FNA). METHODS: Over a 6
      year period, in a retrospective, multicenter study, patients had the diagnosis of
      pancreatic metastases confirmed with EUS-FNA. All examinations were performed by
      one of 5 experienced endosonographers. The EUS and the clinical findings of
      pancreatic metastases were compared with those of a cohort with primary
      pancreatic malignancy. RESULTS: Thirty-seven patients with possible metastases
      were identified, and 13 were excluded because of diagnostic uncertainty. The
      remaining 24 underwent EUS-FNA (mean passes 4.1) of a pancreatic mass without
      complications. Diagnoses included metastases from primary kidney (10), skin (6),
      lung (4), colon (2), liver (1), and stomach (1) cancer. In 4 (17%), 16 (67%), and
      24 (100%) patients, EUS-FNA provided the initial diagnosis of malignancy, tumor
      recurrence, and pancreatic metastases, respectively. Four (17%) metastases
      initially were discovered by EUS after negative (n = 3) or inconclusive (n = 1)
      CT scans. Compared with primary cancer, pancreatic metastases were more likely to
      have well-defined margins (46% vs. 4%) compared with irregular (94% vs. 54%; p <
      0.0001) margins. No statistically significant difference between the two
      populations was noted for tumor size, echogenicity, consistency, location, lesion
      number, or number of FNA passes performed. CONCLUSIONS: Pancreatic metastases are
      an important cause of focal pancreatic lesions and may occasionally be discovered
      during EUS examination after previously negative or inconclusive CT. Use of
      immunocytochemistry, when available, may help to confirm a suspected diagnosis.
      These lesions are more likely to have well-defined EUS margins compared with
      primary pancreatic cancer.

PMID- 15855974
TI  - Endoscopic US for metastases to the pancreas: chasing the satellites.

PMID- 15855975
TI  - EUS-guided FNA of solid pancreatic masses: a learning curve with 300 consecutive
      procedures.
AB  - BACKGROUND: The objective of our study was to assess a single operator's learning
      curve with regard to the number of passes, the diagnostic accuracy, and the
      complications associated with EUS-guided FNA (EUS-FNA) of solid pancreatic
      masses. METHODS: The number of passes, the diagnostic accuracy, and the
      complication rate were prospectively evaluated in 300 consecutive EUS-FNA of
      solid pancreatic masses performed by a single endosonographer over a 3-year
      period. The procedures were placed into 3 groups, which contained 100 procedures
      each. The endosonographer had undergone a third-tier EUS fellowship and had
      performed 45 supervised pancreatic EUS-FNA during his training. RESULTS: Of the
      300 EUS-FNA performed (median age 63 years, 64% men), no statistically
      significant differences among the 3 groups with regard to age, gender, race,
      location, or size of the mass were found. Diagnostic accuracy of the EUS-FNA
      procedure was similar over time (Group 1, 92%; Group 2, 92%; Group 3, 95%).
      Median number of passes showed a decreasing trend over the 3-year study period,
      despite an increasing trend of the number of procedures performed (r = -0.14, p =
      0.42). The median number of passes was lower for Group 2 (median, 3; p = 0.02)
      and Group 3 (median, 3; p = 0.003) compared with Group 1 (median, 4). Group 3
      (7/100, 7%) was less likely to encounter complications compared with Group 1
      (13/100, 13%; p = 0.24) and Group 2 (18/100, 18%; p = 0.03). Frequency of serious
      complications was similar across the 3 groups (1%-3%). CONCLUSIONS: With adequate
      third-tier training, a newly developed EUS program can achieve safe and accurate
      results of EUS-FNA of the pancreas. The learning curve, however, needs to
      continue after the fellowship, because more procedures are needed for one to gain
      proficiency and efficiency with EUS-FNA.

PMID- 15855976
TI  - Predictive factors of positive findings in patients explored by push enteroscopy
      for unexplained GI bleeding.
AB  - BACKGROUND: The diagnostic yield of push enteroscopy (PE) in patients with
      unexplained overt GI bleeding is about 30%. The aim of this study was to assess
      for predictive factors of positive findings. METHODS: A total of 182 patients
      referred to two endoscopic centers (European Georges Pompidou Hospital [Paris,
      France] and Erasmus Hospital [Brussels, Belgium]) for unexplained overt GI
      bleeding (melena [57%], hematochezia [26%], or hematochezia associated with
      melena [17%]) were included in this retrospective study. Predictive factors
      associated with positive findings at upper PE were studied by using uni- and
      multivariate analysis. RESULTS: The overall diagnostic yield of upper PE was 34%
      (62/182), but lesions were found beyond the second duodenum in 25% of the
      patients (45/182). Factors significantly associated with positive findings at
      upper PE were the following. (1) In univariate analysis: the presence of melena,
      Hb level <7 g/dL, blood transfusion >4 units per patient, chronic renal failure,
      disorder of hemostasis or effective anticoagulant treatment, history of
      intestinal arteriovenous malformation, and age > 65 years. (2) In multivariate
      analysis: chronic renal failure and presence of melena. If only jejunal lesions
      were considered, chronic renal failure was the only predictive factor associated
      with positive findings at upper PE in multivariate analysis. The severity of GI
      bleeding did not reach statistical significance ( p = 0.06). Delay between GI
      bleeding and PE, number of previous standard endoscopies and previous episodes of
      bleeding were not associated with positive findings in upper PE. CONCLUSIONS: In
      patients with unexplained overt GI bleeding, upper PE has a higher diagnostic
      yield in patients with chronic renal failure and patients with melena (vs.
      hematochezia).

PMID- 15855977
TI  - Image documentation of endoscopic findings in ulcerative colitis: photographs or
      video clips?
AB  - BACKGROUND: Previous studies have shown deficiencies in the endoscopy reports and
      substantial interobserver variation in the assessments of endoscopic findings.
      The aim of this study was to determine how to perform systematic digital image
      documentation in ulcerative colitis and to evaluate if mucosal inflammation is
      assessed equally on a still image and on a video clip. METHODS: Eighteen video
      clips and their corresponding photographs that visualize different severities of
      ulcerative colitis were shown in randomized order to 20 experienced endoscopists.
      They assessed the mucosal inflammation of each image twice on a visual analog
      scale. Three comparisons were performed between the video clips, the photographs,
      and the video clips to the photographs, respectively. RESULTS: The mean score of
      the inflammation of the video clips at tape 1 and 2 was 4.74: 95% confidence
      interval (CI)[4.41, 5.08] and 4.90: 95% CI[4.56, 5.24), respectively, and of the
      photographs 4.53: 95% CI[4.19, 4.88] and 4.43: 95% CI[4.09, 4.77], respectively.
      The first answer explains 83% of the variation in the second answer for all
      comparisons, and the agreement index ranged from 0.38 to 0.42. CONCLUSIONS: The
      mucosal inflammation might be documented nearly as well with a still image as on
      a video clip. Systematic use of still images probably improves the endoscopy
      reports by adding more objective information about the mucosal inflammation.

PMID- 15855978
TI  - A prospective trial comparing wireless capsule endoscopy and barium contrast
      series for small-bowel surveillance in hereditary GI polyposis syndromes.
AB  - BACKGROUND: Capsule endoscopy has demonstrated its clinical utility in the
      evaluation of the small bowel, and, accordingly, it has been suggested that it
      could be useful for the identification of small-intestinal polyps in patients
      with polyposis syndromes. The objective was to establish the effectiveness of
      wireless capsule endoscopy for detecting small-bowel polyps in patients with
      hereditary GI polyposis syndromes in comparison with barium contrast series.
      METHODS: Consecutive patients with GI polyposis syndromes were included. Small
      bowel follow-through series and capsule endoscopy were performed within 1 week,
      in a blind fashion. The number and the location of polyps were analyzed. RESULTS:
      Twenty-four patients with familial adenomatous polyposis (n = 20) or Peutz
      Jeghers syndrome (n = 4) were included. Capsule endoscopy detected small-bowel
      polyps in 7 of 24 patients (29%), whereas a barium contrast study identified
      small-intestinal polyps in only 3 of these 7 patients. In the 4 remaining
      patients, all of them with familial adenomatous polyposis, polyps detected by the
      capsule but missed in radiographic series were located at either ileum (2
      patients), jejunum (1), or duodenum (1). No procedure-related complication was
      observed in any patient. CONCLUSIONS: Wireless capsule endoscopy is a highly
      accurate technique for the detection of small-bowel polyps in patients with
      hereditary GI polyposis syndromes, and it represents a valuable alternative to
      barium contrast series in the surveillance of patients with Peutz-Jeghers
      syndrome.

PMID- 15855979
TI  - Grant writing and academic survival: what the fellow needs to know.

PMID- 15855981
TI  - Fundal variceal hemorrhage treated by endoscopic clip.

PMID- 15855982
TI  - Functional imaging of a colon polyp.

PMID- 15855983
TI  - Endoscopic band ligation for rectal variceal bleeding: serial colonoscopic
      images.

PMID- 15855984
TI  - Effectiveness of glycerol as a submucosal injection for EMR.
AB  - BACKGROUND: EMR traditionally is performed by using normal saline solution (NS)
      as the submucosal fluid cushion. It is thought, however, that NS does not
      maintain the proper mucosal elevation for EMR of large, flat lesions. We
      investigated the efficacy of glycerol as the submucosal injection solution.
      METHODS: A total of 110 colorectal laterally spreading tumors (LST) were treated
      by EMR with glycerol. For comparison, 113 LSTs treated by using NS were studied.
      The en bloc resection, complete resection, and associated complications rates
      were evaluated retrospectively. OBSERVATIONS: The en bloc resection rate in the
      glycerol group was 63.6% (70/110) compared with 48.9% (55/113) in the NS group (p
      < 0.05). The complete resection rate in the glycerol group was 45.5% (50/110)
      compared with 24.6% (28/113) in the NS group (p < 0.01). The associated
      complications rate was similar in both groups. CONCLUSIONS: It technically was
      easier and as safe to perform EMR of colorectal LSTs when using glycerol as the
      submucosal injection solution.

PMID- 15855985
TI  - Feasibility and safety of string, wireless capsule endoscopy in the diagnosis of
      Barrett's esophagus.
AB  - BACKGROUND: Capsule endoscopy is a major technological advancement in the
      visualization of the small bowell. Its utility in the evaluation of the esophagus
      is mainly limited by its rapid and unpredictable transmission, thus limiting the
      number of pictures of the esophagus, in particular, the distal esophagus.
      METHODS: Strings were attached to the wireless capsule endoscopy device to allow
      its controlled movement up and down the esophagus. Microbiologic cultures of the
      capsule's surface after high-level disinfection were carried out after the
      procedure. At the time of recording, discomfort associated with the procedure was
      documented. Patient preference compared with conventional EGD was recorded. An
      independent endoscopist blinded to the EGD diagnoses assessed the diagnostic
      accuracy of pictures obtained. OBSERVATIONS: Fifty patients with Barrett's
      esophagus were enrolled: 28 with short-segment Barrett's and 22 with long-segment
      Barrett's. The procedure was safe (no strings were disrupted, and no capsule was
      lost), and it rendered negative microbiologic cultures after high-level
      disinfection. The mean recording time was 7.9 minutes; all patients with both
      short- and long-segment Barrett's esophagus were successfully identified. The
      difficulty/discomfort associated with swallowing the device, throat discomfort,
      gagging, moving the capsule (up and down and upon retrieval of the capsule) was
      none or minimal in 74%, 98%, 96%, 94%, and 76%, respectively. A single capsule
      was used in 24 studies, and the majority of patients (92%) preferred string
      capsule endoscopy to EGD. CONCLUSIONS: String-capsule endoscopy was feasible,
      safe, and highly acceptable, and was preferred by patients and may prove to be
      more cost effective than screening EGD.

PMID- 15855986
TI  - Ethanol lavage of pancreatic cystic lesions: initial pilot study.
AB  - BACKGROUND: Ethanol lavage has been used to successfully and safely ablate cystic
      lesions of the liver, the kidneys, and the thyroid. METHODS: Asymptomatic
      patients who undergo EUS examination for a pancreatic cystic lesion were
      eligible. Patients underwent complete examination with a linear-array
      echoendoscope, and cyst characteristics were documented. After evacuation of the
      cyst with needle aspiration, the cyst cavity was lavaged with ethanol for 3 to 5
      minutes. The concentration (5%-80%) of ethanol was gradually increased over the
      course of the study. Patients were monitored for complications during 2 hours
      after the procedure, and further follow-up was obtained at 72 hours and 1 year
      after lavage. OBSERVATIONS: Twenty-five patients were enrolled, 80% were women,
      and the mean age of all patients was 64.5 years. Cysts had a mean diameter of
      19.4 mm and were equally located in the head, the body, and the tail of the
      pancreas. Cyst-fluid characteristics included high viscosity in 13 (52%) and a
      mean carcinoembryonic antigen and amylase of 5916 ng/mL and 11,506 U/L,
      respectively. None of the patients reported any symptoms in short- and long-term
      follow-up. Of the 23/25 patients with complete follow-up, 8 patients (35%) had
      complete resolution of their cysts on follow-up imaging. Five patients underwent
      resection, and histologic evidence of epithelial ablation was seen. CONCLUSIONS:
      Ethanol lavage of pancreatic cystic lesions is safe and feasible. A subset of
      patients undergoing ethanol lavage appears to have long-term resolution on follow
      up imaging. Further prospective studies are required to determine if ethanol
      lavage is an effective treatment for pancreatic cystic lesions.

PMID- 15855987
TI  - Complications involving the mediastinum after injection of Enteryx for GERD.

PMID- 15855988
TI  - Detachable nylon loop assisted removal of large clinically significant colonic
      lipomas.

PMID- 15855989
TI  - Mid esophageal diverticulum with a bleeding ulcer: Case report and review.

PMID- 15855990
TI  - Panenteric melanosis: an ominous endoscopic finding.

PMID- 15855991
TI  - Closure of a benign tracheoesophageal fistula by using a coated, self-expanding
      plastic stent in a patient with a history of esophageal atresia.

PMID- 15855992
TI  - ShapeLock: a rapid access port for redeployment of a colonoscope into the
      proximal colon to facilitate multiple polypectomies in a single session.

PMID- 15855993
TI  - Posttraumatic splenic abscess with gastrosplenic fistula.

PMID- 15855994
TI  - Esophageal sinus formation as a complication of cyanoacrylate injection.

PMID- 15855995
TI  - Endoscopic appearance of GI mycobacteriosis caused by the Mycobacterium avium
      complex in a patient with AIDS: case report and review.

PMID- 15855996
TI  - Double-balloon enteroscopy for diagnosis of a Meckel's diverticulum in a patient
      with GI bleeding of obscure origin.

PMID- 15855997
TI  - Routine colonoscopy complicated by small-bowel obstruction.

PMID- 15855998
TI  - Spontaneous rupture of a biliary diverticulum in the distal common bile duct,
      with formation of a retroperitoneal biloma.

PMID- 15855999
TI  - Flat-type primary malignant melanoma of the esophagus treated by EMR: Case
      report.

PMID- 15856000
TI  - Esophageal, submucosal, gland duct adenoma: role of EUS for endoscopic removal.

PMID- 15856001
TI  - Right hemicolectomy remains the treatment of choice for adenocarcinoma of the
      appendix.

PMID- 15856002
TI  - International survey of EUS practice.

PMID- 15856003
TI  - Formulas for calculating the depth of insertion for the upper and lower
      esophageal sphincters.

PMID- 15856004
TI  - Propofol in endoscopy: why higher risk?

PMID- 15856005
TI  - The antiapoptotic effect of fibroblast growth factor-2 is mediated through
      nuclear factor-kappaB activation induced via interaction between Akt and IkappaB
      kinase-beta in breast cancer cells.
AB  - Fibroblast growth factor-2 (FGF-2) is known for its mitogenic and motogenic
      effects on breast cancer cells. Here, we demonstrate that FGF-2 is also a potent
      stimulator of breast cancer cell survival, as it counteracts the apoptotic
      activity of the C2 ceramide analogue and various chemotherapeutic agents (5
      fluorouracil, camptothecin, etoposide) in MCF-7, T47-D and BT-20 cells. The use
      of pharmacological inhibitors (PD98059, wortmannin, LY294002, SN50) and
      transfection with negative dominants (IkappaBm, p110(PI3K (phosphoinositide 3
      kinase))*DeltaK, AktND) or small interfering RNA targeted against Akt indicated
      that PI3K/Akt and nuclear factor-kappaB (NF-kappaB), but not p42/p44 MAP-kinases,
      were required to stimulate FGF-2 antiapoptotic activity. The activation of NF
      kappaB was dependent on PI3K/Akt, and using a combination of approaches based on
      immunoprecipitation, Western blotting and proteomics (two-dimensional
      electrophoresis and mass spectrometry), we identified the beta form of IkappaB
      kinase (IKKbeta) as a target of Akt signaling. The selective disruption of
      IKKbeta using small interfering RNA induced a potent inhibition of Akt-mediated
      activation of NF-kappaB and cell survival, indicating the functional involvement
      of IKKbeta in FGF-2 antiapoptotic signaling. Together, these results demonstrate
      Akt/IKKbeta interaction in NF-kappaB pathways, thereby emphasizing the potential
      of these proteins as therapeutic targets in breast cancer.

PMID- 15856006
TI  - 53BP1 is associated with replication protein A and is required for RPA2
      hyperphosphorylation following DNA damage.
AB  - p53-binding protein 1 (53BP1) acts as an 'adaptor/mediator' for transducing DNA
      damage signals, especially following detection of DNA double-strand breaks. In an
      effort to broaden our understanding of the protein network surrounding 53BP1, we
      isolated possible 53BP1 binding partners by co-immunoprecipitation, and
      identified them via tandem mass spectrometric analysis. The 53BP1-associated
      proteins included RPA1 and RPA2, two components of the replication protein A
      (RPA) complex. The presence of RPA components in the immunoprecipitates was
      confirmed by immunoblotting, and we found that the association between 53BP1 and
      RPA2 was disrupted following DNA damage induced by treatment with camptothecin, a
      topoisomerase I inhibitor. To investigate the functional meaning of the 53BP1 and
      RPA interaction, we established U2OS osteosarcoma cell lines stably expressing
      dominant-negative fragments of 53BP1. We found that camptothecin-induced RPA2
      phosphorylation was inhibited in these cells, and also following 53BP1 knockdown
      by siRNA transfection. On the cellular level, camptothecin-induced apoptosis was
      augmented in the dominant-negative cell lines, resulting in increased
      chemosensitivity to this drug. Taken together, these results suggest that 53BP1
      is involved in DNA damage-induced RPA2 hyperphosphorylation, and inhibition of
      53BP1 function may sensitize cancer cells to camptothecin treatment.

PMID- 15856007
TI  - A-Raf and Raf-1 work together to influence transient ERK phosphorylation and Gl/S
      cell cycle progression.
AB  - The Raf/MEK/ERK (extracellular regulated kinase) signal transduction pathway
      controls the ability of cells to respond to proliferative, apoptotic, migratory
      and differentiation signals. We have investigated the combined contribution of A
      Raf and Raf-1 isotypes to signalling through this pathway by generating mice with
      knockout mutations of both A-raf and raf-1 genes. Double knockout (DKO) mice have
      a more severe phenotype than single null mutations of either gene, dying in
      embryogenesis at E10.5. The DKO embryos show no changes in apoptosis, but
      staining for Ki67 indicates a generalized reduction in proliferation. DKO mouse
      embryonic fibroblasts (MEFs) exhibit a delayed ability to enter S phase of the
      cell cycle. This is associated with a reduction in levels of transiently induced
      MEK and ERK phosphorylation and reduced expression of c-Fos and cyclin Dl. Levels
      of sustained ERK phosphorylation are not significantly altered. Thus, Raf-1 and A
      Raf have a combined role in controlling physiological transient ERK activation
      and in maintenance of cell cycle progression at its usual rate.

PMID- 15856008
TI  - ZAP-70 upregulation in transformed B cells after early pre-BI cell transplant
      into NOD/SCID mice.
AB  - Understanding of the signal transduction pathways that lead to B cell development
      is of extreme interest to learn how alterations in these pathways might initiate
      malignant transformation. Long-term cultured early pre-BI cells can differentiate
      into IgM+ B cells after transplant into NOD/SCID mice, offering the possibility
      to explore checkpoints in B cell development. Using DNA microarray and Western
      blot analysis of IgM+ B cells vs parental early pre-BI cells, we demonstrated
      that zeta-associated protein 70 (ZAP-70) is upregulated in our B cell
      differentiation model. Unlike parental ZAP-70- early pre-BI cells, ZAP-70+ IgM+ B
      cells exhibited a transformed phenotype, as indicated by BCL-6 expression, a high
      Ki-67 proliferation index, resistance to IL-7 deprivation-induced apoptosis, and
      an increased repopulation rate in NOD/SCID mice. These data show the
      characterization and generation of a novel murine leukemia model with many
      similarities to human ZAP-70+ B cell chronic lymphocytic leukemia.

PMID- 15856009
TI  - Elevated expression of survivin-splice variants predicts a poor outcome for soft
      tissue sarcomas patients.
AB  - The aim of this study was to investigate the level and the prognostic value of
      the expression of different survivin transcript variants--survivin, survivin
      DeltaEx3 and survivin-2B--in tumours of 76 soft tissue sarcoma (STS) patients.
      The expression of survivin transcript variants in STS tissue samples and in 12
      nonmalignant control tissues was analysed by quantitative RT-PCRs. Expression
      levels of all survivin transcript variants were strongly elevated in STS compared
      to normal tissues. A positive correlation between expression of splice variants
      and tumour stage was found (P=0.02; chi2 test). The multivariate Cox's
      proportional hazards regression model revealed a 7.3-fold increased risk of
      tumour-related death for patients with survivin-DeltaEx3 overexpressing tumours
      (P=0.007). The effect of surivivin (wildtype variant) and survivin-2B was less
      pronounced but still significant (2.2- and 1.9-fold, resp., P<0.05 each). Our
      results show for the first time that mRNA expression of survivin-variants is
      significantly correlated to a poor prognosis for STS patients, and we suggest
      expression of survivin splice variants together with tumour stage as independent
      predictor of survival.

PMID- 15856010
TI  - Crosstalk between the human papillomavirus E2 transcriptional activator and the
      E6 oncoprotein.
AB  - Human papillomaviruses are the causative agents of cervical cancer. Previous
      studies have shown that loss of the viral E2 protein during malignant progression
      is an important feature of HPV-induced malignancy due to the resulting
      uncontrolled expression of the viral oncoproteins E6 and E7. We now show however
      that the viral E2 and E6 proteins are both capable of regulating each other's
      activity. When coexpressed, E2 and E6 induce marked changes in the pattern of
      each other's expression, with preferential accumulation in nuclear speckles. The
      two proteins interact directly, resulting in changes in the substrate
      specificities of E6 and the biochemical activities of E2. Thus, while E6
      efficiently degrades its PDZ domain-containing substrates in the absence of E2,
      this activity is greatly diminished when E2 is present. Likewise, E2 alone drives
      both viral DNA replication and viral gene expression. However, in the presence of
      E6, viral DNA replication is inhibited while the transcriptional activity of E2
      is elevated. These studies define a far more complex pattern of interaction
      between E2 and E6 than was previously thought and redefines the possible
      consequences of loss of E2 with respect to uncontrolled E6 activity and
      consequent malignant progression.

PMID- 15856011
TI  - The eleven-nineteen-leukemia protein ENL connects nuclear MLL fusion partners
      with chromatin.
AB  - Mixed lineage leukemia (MLL) fusion proteins are derived from translocations at
      11q23 that occur in aggressive subtypes of leukemia. As a consequence, MLL is
      joined to different unrelated proteins to form oncogenic transcription factors.
      Here we demonstrate a direct interaction between several nuclear MLL fusion
      partners and present evidence for a role of these proteins in histone binding. In
      two-hybrid studies, ENL interacted with AF4 and AF5q31 as well as with a fragment
      of AF10. A structure-function analysis revealed that the AF4/AF5q31/AF10 binding
      domain in ENL coincided with the C-terminus that is essential for transformation
      by MLL-ENL. The ENL/AF4 association was corroborated by GST-pulldown experiments
      and by mutual coprecipitation. Both proteins colocalized in vivo in a nuclear
      speckled pattern. Moreover, AF4 and ENL coeluted on sizing columns together with
      the known ENL binding partner Polycomb3, suggesting the presence of a
      multiprotein complex. The overexpression of ENL alone activated a reporter
      construct and a mutational screen indicated the conserved YEATS domain as
      essential for this function. Overlay and pulldown-assays finally showed a
      specific and YEATS domain-dependent association of ENL with histones H3 and H1.
      In summary, our studies support a common role for nuclear MLL fusion partners in
      chromatin biology.

PMID- 15856012
TI  - Identification of pigment epithelium-derived factor as a direct target of the p53
      family member genes.
AB  - p63 and p73 show a high degree of structural homology to p53 and are members of a
      family of transcriptional factors that can activate transcription of p53
      responsive genes. p53 is mutated in more than 50% of human cancers, whereas p63
      and p73 are rarely mutated. Studies of knockout mice also revealed an unexpected
      functional diversity among the p53 family. To determine how p63 and p73 are
      involved in tumorigenesis and normal development, we used cDNA microarray to
      examine 9216 genes in human colorectal cancer cells. We discovered that the
      expression of pigment epithelium-derived factor (PEDF) was specifically induced
      by either p63 or p73, but not by p53. We also report here that the PEDF gene
      contains a response element specific for p63 and p73 in its promoter region and
      is a direct target of p63 and p73. Collectively, p63 and p73 may be involved in
      cell fate by inducing PEDF expression.

PMID- 15856013
TI  - Human papillomavirus type 16 E6 and E7 oncoproteins upregulate c-IAP2 gene
      expression and confer resistance to apoptosis.
AB  - Inhibition of apoptosis plays an important role in the cellular immortalization
      and transformation induced by E6 and E7 oncoproteins of human papillomavirus
      (HPV). Here, we report that the transcription of the inhibitor of apoptosis gene,
      cellular inhibitor of apoptosis protein 2, (c-IAP2), is significantly upregulated
      in HPV16 E6/E7-immortalized human oral keratinocytes (HOK16E6E7). Overexpression
      of E6/E7 from the high-risk HPV16 or 18, but not from the low-risk HPV6,
      activated c-IAP2 promoter. E6 from HPV16 and 18 played a major role in the
      activation. In addition, the induction of c-IAP2 transcription required nuclear
      factor-kappaB activity. Overexpression of c-IAP2 in normal human oral
      keratinocyte conferred resistance to tumor necrosis factor-alpha (TNF
      alpha)/cycloheximide (CHX)-induced apoptosis, suggesting the increased c-IAP2
      expression in HOK16E6E7 may protect the cells from TNF-alpha-mediated cell death.
      Moreover, depletion of endogenous c-IAP2 using RNA interference in HOK16E6E7
      induced apoptosis, indicating that c-IAP2 is necessary for HPV16 E6/E7-induced
      resistance to apoptosis and cell survival. Of note, high levels of c-IAP2
      transcription were found in several HPV16- or HPV18-positive cancer cells, and
      depletion of c-IAP2 caused cell death in HPV18-positive HeLa cells. Thus,
      upregulation of c-IAP2 by E6 and E7 may confer resistance to apoptosis that is
      necessary for sustained growth of some HPV16- and HPV18-positive cancer cells.

PMID- 15856014
TI  - A single acute exposure to a chemotherapeutic agent induces hyper-recombination
      in distantly descendant cells and in their neighbors.
AB  - Homologous recombination can induce tumorigenic sequence rearrangements. Here, we
      show that persistent hyper-recombination can be induced following exposure to a
      bifunctional alkylating agent, mitomycin C (MMC), and that the progeny of exposed
      cells induce a hyper-recombination phenotype in unexposed neighboring cells.
      Residual damage cannot be the cause of delayed recombination events, since
      recombination is observed after drug and template damage are diluted over a
      million-fold. Furthermore, not only do progeny of MMC-exposed cells induce
      recombination in unexposed cells (bystanders), but these bystanders can in turn
      induce recombination in their unexposed neighbors. Thus, a signal to induce
      homologous recombination can be passed from cell to cell. Although the underlying
      molecular mechanism is not yet known, these studies reveal that cells suffer
      consequences of damage long after exposure, and that can signal unexposed
      neighboring cells to respond similarly. Thus, a single acute exposure to a
      chemotherapeutic agent can cause long-term changes in genomic stability. If the
      results of these studies of mouse embryonic stem (ES) cells are generally
      applicable to many cell types, these results suggest that a relatively small
      number of cells could potentially induce a tissue-wide increase in the risk of de
      novo homologous recombination events.

PMID- 15856015
TI  - Loss of TGF-beta type II receptor in fibroblasts promotes mammary carcinoma
      growth and invasion through upregulation of TGF-alpha-, MSP- and HGF-mediated
      signaling networks.
AB  - Stromal fibroblasts regulate epithelial cell behavior through direct and indirect
      cell-cell interactions. To clarify the role of TGF-beta signaling in stromal
      fibroblasts during mammary development and tumorigenesis, we conditionally
      knocked out the TGF-beta type II receptor gene in mouse mammary fibroblasts
      (Tgfbr2(fspKO)). Tgfbr2(fspKO) mice exhibit defective mammary ductal development,
      characterized in part by increased ductal epithelial cell turnover associated
      with an increase in stromal fibroblast abundance. Tgfbr2(fspKO) mammary
      fibroblasts transplanted with mammary carcinoma cells promote growth and
      invasion, which is associated with increased activating phosphorylation of the
      receptors: erbB1, erbB2, RON, and c-Met. Furthermore, the increased receptor
      phosphorylation correlates with increased secretion of the cognate ligands by
      Tgfbr2(fspKO) fibroblasts. Treatment of tumor cells with fibroblast-conditioned
      medium leads to increased tumor cell proliferation and motility, which are
      blocked by addition of pharmacologic inhibitors of TGF-alpha signaling or
      neutralizing antibodies to macrophage-stimulating protein (MSP), HGF, or c-Met.
      These studies characterize a significant role for stromal TGF-beta signaling in
      mammary tissue homeostasis and mammary tumor progression via regulation of TGF
      alpha, MSP, and HGF signaling pathways.

PMID- 15856016
TI  - A mutation hotspot at the p14ARF splice site.
AB  - Germline mutations of CDKN2A that affect the p16INK4a transcript have been
      identified in numerous melanoma pedigrees worldwide. In the UK, over 50% of
      pedigrees with three or more cases of melanoma have been found to carry mutations
      of CDKN2A. Mutations that affect p14ARF exon 1beta exclusively are very rare.
      This has led to the suggestion that it is p16INK4a and not p14ARF that plays the
      critical role in melanoma predisposition. We report the identification of a
      cluster of five different germline mutations at the p14ARF exon 1beta splice
      donor site in melanoma pedigrees. All the five splice site variants showed
      evidence of being causal mutations. Three of the variants were demonstrated to
      result in aberrant splicing of the p14ARF mRNA, confirming their role in melanoma
      predisposition. No other point mutations were identified in the coding region of
      p14ARF. The p14ARF transcript of CDKN2A is clearly important in disease
      predisposition in a subset of melanoma pedigrees. Curiously, the only mutations
      so far reported to affect p14ARF exon 1beta exclusively have been knockout
      mutations. Further investigation into the spectrum of mutations observed in this
      gene may help clarify the exact role of p14ARF in melanoma predisposition.

PMID- 15856017
TI  - Increased dosage of Runx1/AML1 acts as a positive modulator of myeloid
      leukemogenesis in BXH2 mice.
AB  - The RUNX1/AML1 gene on chromosome 21 is most frequently inactivated in human
      leukemias. In addition, an increased dose of RUNX1 is suggested as a basis for
      several kinds of leukemias. Amplifications of chromosome 21 or the RUNX1 gene are
      shown to be associated with leukemias with lymphoid lineage, whereas its
      involvement in myeloid lineage remains unclear. In this study, we generated GATA
      1 promoter-driven Runx1 transgenic (Tg) mice, which showed a transient mild
      increase of megakaryocyte marker-positive myeloid cells but no spontaneous
      leukemia. These mice were then crossed with BXH2 mice, which have a replication
      competent retrovirus in the mouse and develop myeloid leukemia due to insertional
      mutagenesis by random integration of the virus. Overexpressed Runx1 transgene in
      BXH2 mice resulted in shortening of the latency of leukemia with increased
      frequency of megakaryoblastic leukemia, suggesting that increased Runx1 dosage is
      leukemogenic in myeloid lineage. Identifications of retroviral integration sites
      revealed the genetic alterations that may cooperate with Runx1 overdose in
      myeloid leukemogenesis. This mouse model may be useful for analysing the
      pathogenesis of myeloid leukemias with RUNX1 overdose, especially to examine
      whether an extra-copy of RUNX1 by trisomy 21 is causally related to Down's
      syndrome-related acute megakaryoblastic leukemia (DS-AMKL).

PMID- 15856018
TI  - Oxidized guanine lesions and hOgg1 activity in lung cancer.
AB  - In humans, the oxidatively induced DNA lesion 8-hydroxyguanine (8-oxoG) is
      removed from DNA by hOgg1, a DNA glycosylase/AP lyase that specifically incises 8
      oxoG opposite cytosine. We analysed the expression of hOGG1 mRNA in 18 lung
      cancer and three normal cell lines. Although hOGG1 was overexpressed in most cell
      lines, 2/18 (11.1%) showed a lower hOGG1 mRNA and protein expression
      (approximately 80% decrease) relative to normal cell lines. Liquid
      chromatography/mass spectrometry analysis showed increased levels of 8-oxoG in
      the two cell lines with the lowest hOGG1 mRNA expression. We examined the ability
      of nuclear and mitochondrial extracts to incise 8-oxoG lesion in cell lines H1650
      and H226 expressing lower hOGG1 mRNA and H1915 and H1975 with higher than normal
      hOGG1 mRNA expression. Both nuclear and mitochondrial extracts from H1915 and
      H1975 cells were proficient in 8-oxoG removal. However, both cell lines with the
      lowest hOGG1 mRNA expression exhibited a severe reduction in 8-oxoG incision in
      both nuclear and mitochondrial extracts. Under-expression of hOGG1 mRNA and hOgg1
      protein was associated with a decrease in mitochondrial DNA repair in response to
      oxidative damaging agents. These results provide evidence for defective incision
      of 8-oxoG in both nuclear and mitochondria of H1650 and H226 lung cancer cell
      lines. These results may implicate 8-oxoG repair defects in certain lung cancers.

PMID- 15856019
TI  - Mitogenic signaling by lysophosphatidic acid (LPA) involves Galpha12.
AB  - Lysophosphatidic acid (LPA), a major G protein coupled receptor (GPCR)-activating
      ligand present in serum, elicits growth factor like responses by stimulating
      specific GPCRs coupled to heterotrimeric G proteins such as G(i), G(q), and
      G12/13. Previous studies have shown that the overexpression of wild-type Galpha12
      (Galpha12WT) results in the oncogenic transformation of NIH3T3 cells (Galpha12WT
      NIH3T3) in a serum-dependent manner. Based on the potent growth-stimulating
      activity of LPA and the presence of LPA and LPA-like molecules in the serum, we
      hypothesized that the serum-dependent neoplastic transformation of Galpha12WT
      NIH3T3 cells was mediated by the stimulation of LPA-receptors (LPARs) by LPA in
      the serum. In the present study, using guanine nucleotide exchange assay and GST
      TPR binding assay, we show that the treatment of Galpha12WT-NIH3T3 with 2 muM LPA
      leads to the activation of Galpha12. Stimulation of these cells with LPA promotes
      JNK-activation, a critical component of Galpha12-response and cell proliferation.
      We also show that LPA can substitute for serum in stimulating JNK-activity, DNA
      synthesis, and proliferation of Galpha12WT-NIH3T3 cells. LPA-mediated
      proliferative response in NIH3T3 cells involves Galpha12, but not the closely
      related Galpha13. Pretreatment of Galpha12WT-NIH3T3 cells with suramin (100
      microM), a receptor-uncoupling agent, inhibited LPA-stimulated proliferation of
      these cells by 55% demonstrating the signal coupling between cell surface LPAR
      and Galpha12 in the neoplastic proliferation of NIH3T3 cells. As LPA and LPAR
      mediated mitogenic pathways have been shown to play a major role in tumor genesis
      and progression, a mechanistic understanding of the signal coupling between LPAR,
      Galpha12, and the downstream effectors is likely to unravel additional targets
      for novel cancer chemotherapies.

PMID- 15856020
TI  - Involvement of EGF receptor and c-Src in the survival signals induced by TGF
      beta1 in hepatocytes.
AB  - Transforming growth factor beta1 (TGF-beta1) belongs to a family of polypeptide
      factors, whose cytostatic and apoptotic functions help restrain the growth of
      mammalian cells. Although solid data established the role of TGF-beta's as
      suppressor factors in tumorigenic processes, in the context of an advanced stage
      of disease, TGF-beta's could also play a pro-oncogenic role. We have previously
      shown that TGF-beta1 induces both pro- and anti-apoptotic signals in foetal rat
      hepatocytes. In this work, we have focused on its anti-apoptotic mechanism. We
      show that TGF-beta1 activates the epidermal growth factor receptor (EGFR) and
      phosphorylates c-Src. EGFR is required for Akt activation. Blocking EGFR
      signalling amplifies the apoptotic response to TGF-beta1. TGF-beta1 induced a
      rapid activation of the tumour necrosis factor-alpha-converting enzyme (TACE/ADAM
      (a disintegrin and metalloprotease) 17). Inhibitors of TACE considerably
      attenuated Akt activation, which suggests that TGF-beta1 activates EGF signalling
      in hepatocytes by promoting shedding of EGF-like ligands. The activation of c-Src
      by TGF-beta1 is EGFR dependent and is required for full Akt phosphorylation and
      cell survival. Inhibition of EGFR does not block the epithelial-mesenchymal
      transition (EMT) induced by TGF-beta1 in hepatocytes, which indicates that
      activation of EGFR plays an essential role in impairing apoptosis, but it is
      dispensable for the EMT process.

PMID- 15856021
TI  - The C-terminal region of S100A4 is important for its metastasis-inducing
      properties.
AB  - The EF-hand protein, S100A4, binds calcium ions and interacts specifically in
      vitro with protein targets. Elevated levels of S100A4 have been shown to produce
      a metastatic phenotype in independent models of breast cancer. The presence of
      S100A4 in the carcinoma cells of patients with different carcinomas is associated
      with reduced patient survival. In order to identify the region of the S100A4
      molecule that is responsible for its metastasis-inducing properties, specific
      mutant S100A4 genes and proteins have been produced which contain targeted
      mutations to the two calcium-binding sites and a deletion of the last 15 amino
      acid residues of the protein. The ability of the mutant proteins to bind to a
      potential specific target in vitro, nonmuscle myosin heavy chain, is correlated
      with their ability to cause motile, invasive and metastatic phenotypes. Mutation
      of the C-EF hand of S100A4 virtually abolished calcium binding, and
      motility/invasion in vitro, abolished interaction with a molecular target, and
      reduced metastasis induction by 2.5-3-fold. However, deletion of the last 15
      amino acids of S100A4 reduced motility/invasion, target binding and metastasis
      induction to similar extents as the C-EF-hand mutant, but reduced calcium binding
      by only 26%. The results suggest that the ability to interact with protein
      target(s) is important in S100A4-induced metastasis.

PMID- 15856022
TI  - Loss of RALT/MIG-6 expression in ERBB2-amplified breast carcinomas enhances ErbB
      2 oncogenic potency and favors resistance to Herceptin.
AB  - An emerging paradigm holds that loss of negative signalling to receptor tyrosine
      kinases (RTKs) is permissive for their oncogenic activity. Herein, we have
      addressed tumor suppression by RALT/MIG-6, a transcriptionally controlled
      feedback inhibitor of ErbB RTKs, in breast cancer cells. Knockdown of RALT
      expression by RNAi enhanced the EGF-dependent proliferation of normal breast
      epithelial cells, indicating that loss of RALT signalling in breast epithelium
      may represent an advantageous condition during ErbB-driven tumorigenesis.
      Although mutational inactivation of the RALT gene was not detected in human
      breast carcinomas, RALT mRNA and protein expression was strongly and selectively
      reduced in ERBB2-amplified breast cancer cell lines. Reconstitution of RALT
      expression in ERBB2-amplified SKBr-3 and BT474 cells inhibited ErbB-2-dependent
      mitogenic signalling and counteracted the ability of ErbB ligands to promote
      resistance to the ErbB-2-targeting drug Herceptin. Thus, loss of RALT expression
      cooperates with ERBB2 gene amplification to drive full oncogenic signalling by
      the ErbB-2 receptor. Moreover, loss of RALT signalling may adversely affect tumor
      responses to ErbB-2-targeting agents.

PMID- 15856023
TI  - Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane
      and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells.
AB  - Recent studies indicate that natural isothiocyanates, such as sulforaphane (SFN)
      and phenethyl isothiocyanate (PEITC) possess strong antitumor activities in vitro
      and in vivo. The nuclear factor kappa B (NF-kappaB) is believed to play an
      important role in cancer chemoprevention due to its involvement in tumor cell
      growth, proliferation, angiogenesis, invasion, apoptosis, and survival. In this
      study, we investigated the effects and the molecular mechanisms of SFN and PEITC
      on NF-kappaB transcriptional activation and NF-kappaB-regulated gene expression
      in human prostate cancer PC-3 C4 cells. Treatment with SFN (20 and 30 microM) and
      PEITC (5 and 7.5 microM) significantly inhibited NF-kappaB transcriptional
      activity, nuclear transloction of p65, and gene expression of NF-kappaB-regulated
      VEGF, cylcin D1, and Bcl-X(L) in PC-3 C4 cells. To further elucidate the
      mechanism, we utilized the dominant-negative mutant of inhibitor of NF-kappaB
      alpha (IkappaBalpha) (SR-IkappaBalpha). Analogous to treatments with SFN and
      PEITC, SR-IkappaBalpha also strongly inhibited NF-kappaB transcriptional activity
      as well as VEGF, cylcin D1, and Bcl-X(L) expression. Furthermore, SFN and PEITC
      also inhibited the basal and UVC-induced phosphorylation of IkappaBalpha and
      blocked UVC-induced IkappaBalpha degradation in PC-3 C4 cells. In examining the
      upstream signaling, we found that the dominant-negative mutant of IKKbeta
      (dnIKKbeta) possessed inhibitory effects similar to SFN and PEITC on NF-kappaB,
      VEGF, cylcin D1, Bcl-X(L) as well as IkappaBalpha phosphorylation. In addition,
      treatment with SFN and PEITC potently inhibited phosphorylation of both IKKbeta
      and IKKalpha and significantly inhibited the in vitro phosphorylation of
      IkappaBalpha mediated by IKKbeta. Taken together, these results suggest that the
      inhibition of SFN and PEITC on NF-kappaB transcriptional activation as well as NF
      kappaB-regulated VEGF, cyclin D1, and Bcl-X(L) gene expression is mainly mediated
      through the inhibition of IKK phosphorylation, particularly IKKbeta, and the
      inhibition of IkappaBalpha phosphorylation and degradation, as well as the
      decrease of nuclear translocation of p65 in PC-3 cells.

PMID- 15856024
TI  - Inhibitory effect of c-Myc on p53-induced apoptosis in leukemia cells. Microarray
      analysis reveals defective induction of p53 target genes and upregulation of
      chaperone genes.
AB  - We have previously demonstrated that c-Myc impairs p53-mediated apoptosis in K562
      human leukemia cells, which lack ARF. To investigate the mechanisms by which c
      Myc protects from p53-mediated apoptosis, we used K562 cells that conditionally
      express c-Myc and harbor a temperature-sensitive allele of p53. Gene expression
      profiles of cells expressing wild-type conformation p53 in the presence of either
      uninduced or induced c-Myc were analysed by cDNA microarrays. The results show
      that multiple p53 target genes are downregulated when c-Myc is present, including
      p21WAF1, MDM2, PERP, NOXA, GADD45, DDB2, PIR121 and p53R2. Also, a number of
      genes that are upregulated by c-Myc in cells expressing wild-type conformation
      p53 encode chaperones related to cell death protection as HSP105, HSP90 and
      HSP27. Both downregulation of p53 target genes and upregulation of chaperones
      could explain the inhibition of apoptosis observed in K562 cells with ectopic c
      Myc. Myc-mediated impairment of p53 transactivation was not restricted to K562
      cells, but it was reproduced in a panel of human cancer cell lines derived from
      different tissues. Our data suggest that elevated levels of Myc counteract p53
      activity in human tumor cells that lack ARF. This mechanism could contribute to
      explain the c-Myc deregulation frequently found in cancer.

PMID- 15856025
TI  - Novel Rap1 dominant-negative mutants interfere selectively with C3G and Epac.
AB  - Rap1 is a Ras-related GTPase that is principally involved in integrin- and E
      cadherin-mediated adhesion. Rap1 is transiently activated in response to many
      incoming signals via a large family of guanine nucleotide exchange factors
      (GEFs). The lack of potent Rap1 dominant-negative mutants has limited our ability
      to decipher Rap1-dependent pathways; we have therefore developed a procedure to
      generate such mutants consisting in the oligonucleotide-mediated mutagenesis of
      residues 14-19, selection of mutants presenting an enhanced interaction with
      Epac2 by yeast two-hybrid screening and counter-screening for mutants still
      interacting with Rap effectors. In detail analysis of their interaction capacity
      with various Rap-GEFs in the yeast two-hybrid system revealed that mutants of
      residues 15 and 16 interacted with Epacs, C3G and CalDAG-GEFI, whereas mutants of
      position 17 had selectively lost their ability to bind CalDAG-GEFI as well as,
      for some, C3G. In cellular models where Rap1 is activated via endogenous GEFs,
      the Rap1[S17A] mutant inhibits both the cAMP-Epac and EGF-C3G pathways, whereas
      Rap1[G15D] selectively interferes with the latter. Finally, Rap1[S17A] is able to
      act as a bona fide dominant-negative mutant in vivo since it phenocopies the eye
      reducing and lethal effects of D-Rap1 deficiency in Drosophila, effects that are
      overcome by the overexpression of D-Epac or D-Rap1.

PMID- 15856026
TI  - Loss of BNIP3 expression is a late event in pancreatic cancer contributing to
      chemoresistance and worsened prognosis.
AB  - Altered expression of apoptosis-regulating genes plays an important role in the
      aggressive growth behavior and chemoresistance of pancreatic ductal
      adenocarcinoma. In the present study, the hypoxia-inducible proapoptotic gene,
      BNIP3, was analysed in terms of expression, effect on patient survival, and chemo
      responsiveness in pancreatic cancer cell lines. cDNA microarray, real-time light
      cycler quantitative polymerase chain reaction, laser-capture microdissection, and
      immunohistochemistry analyses were used to evaluate BNIP3 expression in normal
      and diseased pancreatic specimens. Modulation of BNIP3 expression was achieved
      using specific siRNA molecules. The effect of chemotherapeutic agents on
      pancreatic cancer cells was assessed utilizing 3-(4,5-methylthiazol-2-yl)-2,5
      diphenyl-tetrazolium-bromide assays. BNIP3 mRNA levels were 3.0- and 6.3-fold
      lower in chronic pancreatitis and pancreatic cancer compared to the normal
      pancreas, respectively. Microdissection analysis confirmed the reduction of BNIP3
      expression in pancreatic cancer cells compared to normal duct cells. By
      immunohistochemistry, BNIP3 was predominantly expressed in the acinar cells of
      the normal and diseased pancreas. Interestingly, while BNIP3 was undetectable in
      the cancer cells of 59% of the cases, 75-100% of PanIN2/3 lesions displayed BNIP3
      immunoreactivity. Loss of BNIP3 expression correlated with poorer survival of
      patients (8 vs 14 months for BNIP3 negative vs positive tumors). Hypoxia induced
      BNIP3 expression in four out of eight pancreatic cancer cell lines, while it was
      absent under normoxic and hypoxic conditions in the remaining four.
      Downregulation of BNIP3 resulted in increased resistance to 5-fluoro-uracil and
      gemcitabine. In conclusion, loss of BNIP3 expression occurs late in pancreatic
      cancer, contributes to resistance to chemotherapy, and correlates with a worsened
      prognosis.

PMID- 15856027
TI  - Loss of the LIM domain protein Lmo4 in the mammary gland during pregnancy impedes
      lobuloalveolar development.
AB  - LMO4, a member of the LIM-only family of zinc-finger proteins, is overexpressed
      in a significant proportion of breast carcinomas and acts as a negative regulator
      of mammary epithelial differentiation. To delineate cell types within the
      developing mouse mammary gland that express Lmo4, we analysed different stages of
      mammopoiesis by immunohistochemistry. Lmo4 was found to be highly expressed in
      the proliferating cap cells of the terminal end bud and in the ductal and
      alveolar luminal cells of the mature mammary gland but was negligible or low in
      myoepithelial cells. To assess the physiological role of Lmo4 in the mammary
      gland, we generated conditionally targeted mice lacking Lmo4 in the mammary
      epithelium during pregnancy. Acute loss of Lmo4 in late pregnancy impaired
      lobuloalveolar development, accompanied by a two-fold reduction in the percentage
      of BrdU-positive cells. In contrast, germline loss of Lmo4 did not alter
      lobuloalveolar development arising from transplanted mammary anlagen, implying
      the existence of a compensatory mechanism in these knockout mice. Thus, the use
      of a conditional targeting strategy has revealed that Lmo4 is required for proper
      development of the mammary gland during pregnancy and indicated that Lmo4 acts as
      a positive regulator of alveolar epithelial proliferation.

PMID- 15856029
TI  - A novel retinoid-related molecule inhibits pancreatic cancer cell proliferation
      by a retinoid receptor independent mechanism via suppression of cell cycle
      regulatory protein function and induction of caspase-associated apoptosis.
AB  - Retinoid-related molecules are important potential agents for the treatment of
      cancer. In the present study, we test the effect of a novel retinoid-related
      ligand, AGN193198 (4-[3-(1-heptyl-4,4-dimethyl-2-oxo-1,2,3,4-tetrahydroquinolin-6
      yl)-3-oxo-prophenyl] benzoic acid), on pancreatic cancer cell proliferation and
      survival. AGN193198 treatment reduces BxPC-3 cell proliferation more efficiently
      than high-affinity retinoid acid receptor (RAR)- or retinoid X receptor (RXR)
      selective retinoids. Moreover, AGN193198 does not activate transcription from RAR
      or RXR response elements and its effects on cell survival are not reversed by
      treatment with RAR- or RXR receptor-selective antagonists. These results suggest
      that the AGN193198-dependent inhibition of BxPC-3 cell function is not mediated
      via activation of the classical retinoid receptors. Cell cycle analysis of
      AGN193198-treated BxPC-3 cells indicates that AGN193198 causes accumulation of
      cells in G2/M. This change is associated with a marked reduction in regulators of
      S (cyclin A, cyclin-dependent kinase (cdk)2), G2/M (cyclin B1, cdk1, cdc25c) and
      G1 (cyclin D1, cyclin E, cdk2, cdk4) phase, and an increase in p21 and p27 level.
      Kinases assays reveal that cdk1, cdk2 and cdk4 activity are suppressed in
      AGN193198-treated cells. In addition, reduced cell proliferation is associated
      with enhanced procaspase (3, 8 and 9) and PARP cleavage. Z-VAD-FMK, a pancaspase
      inhibitor, inhibits AGN193198-dependent caspase activation and attenuates cell
      death. Z-VAD-FMK inhibits PARP cleavage, but does not alter the AGN193198
      dependent reduction in cell cycle regulatory protein expression and activity,
      suggesting that caspase activation and suppression of cell cycle regulatory
      protein levels are independent processes. AGN193198 produces similar responses in
      other pancreatic cancer cell lines including AsPC-1 and MIA PaCa-2. These studies
      suggest that AGN193198 may be useful for the treatment of pancreatic cancer.

PMID- 15856028
TI  - Erythropoietin-mediated activation of JAK-STAT signaling contributes to cellular
      invasion in head and neck squamous cell carcinoma.
AB  - Originally characterized as a growth factor for erythrocytes, erythropoietin
      (EPO) is used to treat anemia and fatigue in cancer patients receiving radiation
      therapy and chemotherapy. EPO and the EPO receptor (EPOR) are expressed in
      nonhematopoietic cells and cancers. However, the role of EPO and EPOR within
      nonhematopoietic cancer cells remains incompletely understood. Although a recent
      clinical trial demonstrated worse tumor control and survival in head and neck
      cancer patients treated with EPO, the role of EPO and EPOR in head and neck
      squamous cell carcinoma (HNSCC) has not been examined. In the present study, we
      demonstrate the previously unrecognized EPO-mediated invasion by HNSCC cells
      through the Janus kinase (JAK)-signal transducer and activator of transcription
      (STAT) signaling pathway. Furthermore, we confirmed the expression of EPO and
      EPOR in a panel of human HNSCC cell lines and tissue specimens. Pharmacological
      doses of EPO also had a limited proliferation effect in these cell lines. These
      results define a novel role for EPO in mediating tumor cell invasion. Increased
      levels of EPO and EPOR in lymph node metastases as compared to primary tumors
      from HNSCC patients further support the role of EPO/EPOR in HNSCC disease
      progression and metastasis.

PMID- 15856030
TI  - Oncogenic Ras increases sensitivity of colon cancer cells to 5-FU-induced
      apoptosis.
AB  - Despite the fact that objective response rates to 5-FU are as low as 20%, 5-FU
      remains the most commonly used drug for the treatment of colorectal cancer. The
      lack of understanding of resistance to 5-FU, therefore, remains a significant
      impediment in maximizing its efficacy. We used intestinal epithelial cells with
      an inducible K-RasV12 to demonstrate that expression of oncogenic Ras promotes
      cell death upon 5-FU treatment. Accordingly, transient expression of the mutant
      RasV12, but not the WT Ras, enhanced 5-FU-induced apoptosis in 293T cells.
      Consistent with these data, we showed that targeted deletion of the mutant Ras
      allele in the HCT116 colon cancer cell line protected cells from 5-FU-induced
      apoptosis. Using isogenic colon cancer cell lines that differ only by the
      presence of the mutant Ras allele, HCT116 and Hke-3 cells, we demonstrated that
      signaling by oncogenic Ras promotes both accumulation of p53 and its
      phosphorylation on serine15 in response to 5-FU, a situation that favors
      apoptosis over growth arrest. However, despite the differential induction of p53
      in HCT116 and Hke-3 cells, the expression of Puma, a gene with an important role
      in p53-dependent apoptosis, was not affected by Ras signaling. In contrast, we
      showed that Ras interferes with 5-FU-induced expression of gelsolin, a protein
      with known antiapoptotic activity. We ascertained the role of gelsolin in 5-FU
      induced apoptosis by demonstrating that silencing of gelsolin expression through
      RNAi sensitized cells to 5-FU-induced apoptosis and that re-expression of
      gelsolin in cells harboring mutant Ras protected cells from 5-FU-induced
      apoptosis. These data therefore demonstrate that Ras mutations increase
      sensitivity to 5-FU-induced apoptosis at least in part through the negative
      regulation of gelsolin expression. Our data indicate that Ras mutations promote
      apoptosis in response to 5-FU treatment and imply that tumors with Ras mutations
      and/or reduced expression of gelsolin may show enhanced apoptosis in response to
      5-FU also in vivo.

PMID- 15856031
TI  - Transformed immortalized gastric epithelial cells by virulence factor CagA of
      Helicobacter pylori through Erk mitogen-activated protein kinase pathway.
AB  - CagA of Helicobacter pylori is a protein that has been closely associated with
      gastric cancer and that can intervene with signal pathways in cells. Its precise
      relationship with the occurrence of gastric cancer, however, remains unclear. The
      purpose of this study is to investigate whether CagA can promote transformation
      of normal gastric epithelial cells and to consider via what mechanisms CagA may
      exert its effects. Transformed colonies were merged in soft-agarose medium after
      immortalized gastric epithelial cells were transfected with recombinant pLHCX
      retrovirus with cagA and/or dimethylhydrazine. The number of transformed colonies
      in the group containing cagA/pLHCX retrovirus, combined with a subthreshold dose
      of dimethylhydrazine, was more than that for cagA/pLHCX retrovirus or
      dimethylhydrazine at a subthreshold dose alone. For cagA-transfected cells, only
      IQGAP-2, R-Ras and B-Raf of the Ras/mitogen-activated protein kinase signal
      pathway were markedly increased, and the activity of extracellular signal
      regulated kinase 1/2 (Erk1/2) kinase was significantly higher than that in
      dimethylhydrazine-transformed cells or control cells. However, no evidence of
      alteration of any other molecules of the Ras superfamily was observed in cagA
      transfected cells. These findings suggest that CagA can transform gastric
      epithelial cells through activation of the Erk1/2 pathway; this mechanism may,
      however, be independent of Ras activation.

PMID- 15856032
TI  - P53 abnormalities and outcomes in colorectal cancer: a systematic review.

PMID- 15856034
TI  - An inverse association between tumour size and overdiagnosis may explain the
      results by Bucchi et al.

PMID- 15856035
TI  - Phase II study of sequential hormonal therapy with anastrozole/exemestane in
      advanced and metastatic breast cancer.
AB  - Hormonal therapy is the preferred systemic treatment for recurrent or metastatic,
      post-menopausal hormone-receptor-positive breast cancer. Previous studies have
      shown that there is no cross-resistance between exemestane and reversible
      aromatase inhibitors. Exposure to hormonal therapy does not hamper later response
      to chemotherapy. Patients with locally advanced or metastatic, hormonal receptor
      positive or unknown, breast cancer were treated with oral anastrozole, until
      disease progression, followed by oral exemestane until new evidence of disease
      progression. The primary end point of the study was clinical benefit, defined as
      the sum of complete responses (CR), partial responses (PR) and > 24 weeks stable
      disease (SD). In all, 100 patients were enrolled in the study. Anastrozole
      produced eight CR and 19 PR for an overall response rate of 27% (95% CI: 18.6
      36.8%). An additional 46 patients had long-term (> 24 weeks) SD for an overall
      clinical benefit of 73% (95% CI: 63.2-81.4). Median time to progression (TTP) was
      11 months (95% CI: 10-12). A total of 50 patients were evaluated for the second
      line treatment: exemestane produced one CR and three PR; 25 patients had SD which
      lasted > or = 6 months in 18 patients. Median TTP was 5 months. Toxicity of
      treatment was low. Our study confirms that treatment with sequential hormonal
      agents can extend the period of time during which endocrine therapy can be used,
      thereby deferring the decision to use chemotherapy.

PMID- 15856036
TI  - Intensity-modulated radiation therapy: emerging cancer treatment technology.
AB  - The use of intensity-modulated radiation therapy (IMRT) is rapidly advancing in
      the field of radiation oncology. Intensity-modulated radiation therapy allows for
      improved dose conformality, thereby affording the potential to decrease the
      spectrum of normal tissue toxicities associated with IMRT. Preliminary results
      with IMRT are quite promising; however, the clinical data is relatively immature
      and overall patient numbers remain small. High-quality IMRT requires intensive
      physics support and detailed knowledge of three-dimensional anatomy and patterns
      of tumour spread. This review focuses on basic principles, and highlights the
      clinical implementation of IMRT in head and neck and prostate cancer.

PMID- 15856037
TI  - Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin,
      cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary
      cancer.
AB  - The purpose of this study was to determine whether epirubicin, cisplatin and
      infused 5FU (ECF) improves overall survival (OS) compared to 5FU, etoposide and
      leucovorin (FELV) in patients with previously untreated advanced biliary cancer
      in a prospective randomised study. Patients were randomly assigned to receive
      epirubicin, cisplatin and infused 5FU ECF or bolus 5FU etoposide and leucovorin
      (FELV). The primary end point was OS with secondary end points of objective
      response rate (ORR), failure-free survival (FFS), quality of life (QOL) and
      toxicity. In all, 54 patients were recruited with 27 randomly assigned to each
      arm. The median OS for ECF was 9.02 months (95% confidence interval (CI): 6.46
      11.51) and FELV 12.03 months (95% CI: 9.3-14.7), P=0.2059. Objective response
      rates were similar for both arms: ECF 19.2% (95% CI: 6.55-39.3); FELV 15% (95%
      CI: 3.2-37.9), P=0.72. There was significantly increased grade 3/4 neutropenia
      with FELV vs ECF (53.8 vs 29.5%, respectively, P=0.020). Symptom resolution was
      impressive for both regimens. This is the largest reported randomised study to
      date in this setting. ECF did not improve OS compared to FELV, but was associated
      with less acute toxicity. These data suggest that chemotherapy can prolong OS and
      achieve good symptomatic relief in advanced biliary cancer.

PMID- 15856038
TI  - A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and
      folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer
      patients.
AB  - The aim of the study was to assess the toxicity and the clinical activity of
      biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and
      folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with
      advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients
      were treated with oxaliplatin 85 mg m(-2) on day 1, FA 200 mg m(-2) as a 2 h
      infusion followed by bolus 5-FU 400 mg m(-2) and a 22 h infusion of 5-FU 600 mg
      m(-2), repeated for 2 consecutive days every 2 weeks. All patients were
      assessable for toxicity and response to treatment. Four (7%) complete responses
      and 19 partial responses were observed (overall response rate, 38%). Stable
      disease was observed in 22 (36%) patients, with progressive disease in the other
      six (10%) patients. Median time to progression (TTP) and median overall survival
      (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common
      Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia
      and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3
      peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active
      and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable
      with those of other oxaliplatin-based regimens, suggesting a role for this
      combination in gastric cancer.

PMID- 15856039
TI  - No association between fruit or vegetable consumption and the risk of colorectal
      cancer in Japan.
AB  - In a pooled analysis of two prospective studies with 88,658 Japanese men and
      women, fruit and vegetable consumptions, were not associated with a lower risk of
      colorectal cancer (705 cases); multivariate relative risk (95% confidence
      interval) for the highest vs the lowest quartile of intake being 0.92 (0.70-1.19)
      and 1.00 (0.79-1.27), respectively.

PMID- 15856040
TI  - HMG CoA reductase inhibitors (statins) to treat Epstein-Barr virus-driven
      lymphoma.
AB  - While statins have been highly effective for lowering serum cholesterol and
      reducing the incidence of coronary events, they have multiple other effects.
      Certain statins block the interaction of adhesion molecules that are important
      for cell-cell interactions including those between EBV-transformed B cells. These
      same statins inhibit NF-kappaB activation in the cells and induce apoptosis of
      transformed B cells. Studies in severe combined immunodeficiency mice show that
      simvastatin delays the development of EBV-lymphomas in these animals. These
      statins might be considered for the treatment of EBV-lymphomas in selected
      patients.

PMID- 15856041
TI  - Genome-wide gene expression profiling of testicular carcinoma in situ progression
      into overt tumours.
AB  - The carcinoma in situ (CIS) cell is the common precursor of nearly all testicular
      germ cell tumours (TGCT). In a previous study, we examined the gene expression
      profile of CIS cells and found many features common to embryonic stem cells
      indicating that initiation of neoplastic transformation into CIS occurs early
      during foetal life. Progression into an overt tumour, however, typically first
      happens after puberty, where CIS cells transform into either a seminoma (SEM) or
      a nonseminoma (N-SEM). Here, we have compared the genome-wide gene expression of
      CIS cells to that of testicular SEM and a sample containing a mixture of N-SEM
      components, and analyse the data together with the previously published data on
      CIS. Genes showing expression in the SEM or N-SEM were selected, in order to
      identify gene expression markers associated with the progression of CIS cells.
      The identified markers were verified by reverse transcriptase-polymerase chain
      reaction and in situ hybridisation in a range of different TGCT samples.
      Verification showed some interpatient variation, but combined analysis of a range
      of the identified markers may discriminate TGCT samples as SEMs or N-SEMs. Of
      particular interest, we found that both DNMT3B (DNA (cytosine-5-)
      methyltransferase 3 beta) and DNMT3L (DNA (cytosine-5-)-methyltransferase 3 like)
      were overexpressed in the N-SEMs, indicating the epigenetic differences between N
      SEMs and classical SEM.

PMID- 15856042
TI  - A prospective randomised trial to study the role of levamisole and interferon
      alfa in an adjuvant therapy with 5-FU for stage III colon cancer.
AB  - The purpose of this trial was to examine the efficacy of the addition of
      levamisole (LEV) or interferon alfa (IFN) to an adjuvant chemotherapy with 5
      fluorouracil (5-FU) in patients with stage III colon cancer. According to a 2 x 2
      factorial study design, 598 patients were randomly assigned to one of four
      adjuvant treatment arms. Patients in arm one received 5-FU weekly for 1 year,
      patients in arm two 5-FU plus LEV, in arm three 5-FU plus IFN and patients in arm
      four 5-FU, LEV and IFN. The relative risk of relapse and the relative risk of
      death were significantly higher for patients treated with LEV compared with those
      without LEV treatment (HR 1.452, 95% CI 1.135-1.856, P=0.0028; HR 1.506, 95% CI
      1.150-1.973, P=0.0027, respectively). No significant impact on survival was
      observed for therapy with IFN in the univariate analysis. The addition of LEV to
      adjuvant 5-FU significantly worsened the prognosis of patients with stage III
      colon cancer. Interferon alfa had no significant influence on survival when
      combined with adjuvant 5-FU, but increased the toxicity of therapy substantially.

PMID- 15856043
TI  - A modified Inflammatory Bowel Disease questionnaire and the Vaizey Incontinence
      questionnaire are simple ways to identify patients with significant
      gastrointestinal symptoms after pelvic radiotherapy.
AB  - After radiotherapy for pelvic cancer, chronic gastrointestinal problems may
      affect quality of life (QOL) in 6-78% of patients. This variation may be due to
      true differences in outcome in different diseases, and may also represent the
      inadequacy of the scales used to measure radiotherapy-induced gastrointestinal
      side effects. The aim of this study was to assess whether outcome measures used
      for nonmalignant gastrointestinal disease are useful to detect gastrointestinal
      morbidity after radiotherapy. Results obtained from a Vaizey Incontinence
      questionnaire and a modified Inflammatory Bowel Disease questionnaire (IBDQ)-
      both patient completed--were compared to those from a staff administered Late
      Effects on Normal Tissue (LENT)--Subjective, Objective, Management and Analytic
      (SOMA) questionnaire in patients who had completed radiotherapy for a pelvic
      tumour at least 3 months previously. In all, 142 consecutive patients were
      recruited, 72 male and 70 female, median age 66 years (range 26-90 years), a
      median of 27 (range 3-258) months after radiotherapy. In total, 62 had been
      treated for a gynaecological, 58, a urological and 22, a gastrointestinal tract
      tumour. Of these, 21 had undergone previous gastrointestinal surgery and seven
      suffered chronic gastrointestinal disorders preceding their diagnosis of cancer.
      The Vaizey questionnaire suggested that 27% patients were incontinent for solid
      stools, 35% for liquid stools and 37% could not defer defaecation for 15 min. The
      IBDQ suggested that 89% had developed a chronic change in bowel habit and this
      change significantly affected 49% patients: 44% had more frequent or looser bowel
      movements, 30% were troubled by abdominal pain, 30% were troubled by bloating,
      28% complained of tenesmus, 27% were troubled by their accidental soiling and 20%
      had rectal bleeding. At least 34% suffered emotional distress and 22% impairment
      of social function because of their bowels. The small intestine/colon SOMA median
      score was 0.1538 (range 0-1) and the rectal SOMA median score was 0.1428 (range 0
      1). Pearson's correlations for the IBDQ score and small intestine/colon SOMA
      score was -0.630 (P<0.001), IBDQ and rectum SOMA -0.616 (P<0.001), IBDQ and
      Vaizey scores -0.599 (P<0.001), Vaizey and small intestine/colon SOMA 0.452
      (P<0.001) and Vaizey and rectum SOMA 0.760 (P<0.001). After radiotherapy for a
      tumour in the pelvis, half of all patients develop gastrointestinal morbidity,
      which affects their QOL. A modified IBDQ and Vaizey questionnaire are reliable in
      assessing new gastrointestinal symptoms as well as overall QOL and are much
      easier to use than LENT SOMA.

PMID- 15856044
TI  - Role of fried foods and oral/pharyngeal and oesophageal cancers.
AB  - We investigated the role of fried foods on oral-pharyngeal and oesophageal
      cancers, using data from two case-control studies conducted in Italy and
      Switzerland between 1992 and 1999, one with a total of 749 (634 men) cases of
      oral/pharyngeal cancer and 1772 (1252 men) controls, the other with 395 (351 men)
      cases of oesophageal cancer and 1066 (875 men) controls. Controls were admitted
      for acute, non-neoplastic conditions, unrelated to alcohol and smoking
      consumption. After allowance for sex, age, centre, education, body mass index,
      tobacco smoking, alcohol drinking and nonalcohol energy intake, the multivariate
      odds ratios (ORs) for an increment of one portion per week of total fried foods
      were 1.11 (95% confidence interval (CI): 1.05-1.17) for oral-pharyngeal and 1.16
      (95% CI: 1.08-1.26) for oesophageal cancer. The ORs were consistent across strata
      of gender (OR in men only were 1.10 and 1.16, respectively), age, alcohol,
      tobacco consumption and body mass index.

PMID- 15856045
TI  - Microsatellite instability in colorectal cancer is associated with local
      lymphocyte infiltration and low frequency of distant metastases.
AB  - Colorectal carcinomas (CRCs) with high microsatellite instability (MSI-H) share
      clinicopathological features distinctly different from their microsatellite
      stable (MSS) counterparts. Unlike MSS cancers, MSI-H CRCs occur predominantly in
      the right-sided colon and are often characterised by a strong lymphocyte
      infiltration. A poor differentiation pattern is found in most MSI-H CRCs, even
      though patients with MSI-H carcinomas seem to have a significantly longer
      survival after surgical resection. To clarify which factors contribute to the
      obvious paradoxon of a more favourable prognosis of MSI tumours, several clinical
      and histopathological features as well as the microsatellite status were
      evaluated in 120 colorectal cancer cases fulfilling clinical criteria (Bethesda)
      indicative for familial colorectal cancer. Microsatellite instability status and
      lymphocyte infiltration were related to tumour stage and patients' follow-up.
      Statistical analysis confirmed well-known relations, such as enhanced lymphocyte
      infiltration accompanied by Crohn's like reaction (CLR) in MSI-H cancers (CLR+ in
      27 out of 47 MSI-H vs 14 out of 71 MSS CRCs, P<0.001). However, after
      stratification for depth of local invasion and penetration of the primary tumour,
      T3 tumours displaying MSI had a significantly lower rate of distant metastases
      (M1 in four out of 35 MSI-H vs 20 out of 41 MSS CRCs, P<0.001). A similar
      tendency was observed for CLR-positive CRCs (M1 in six out of 29 CLR+ vs 17 out
      of 45 CLR- CRCs, P=0.13). In a logistic regression model, the MSI-H phenotype and
      the presence of CLR were independent predictors of a low UICC stage (P=0.006 and
      0.04, respectively). These data, together with the recent definition of highly
      immunogenic neo-antigens expressed in MSI-H tumour cells, suggest that MSI-H CRCs
      elicit a protective host response that may prevent metastasis formation.

PMID- 15856046
TI  - Clinicopathological significance of EZH2 mRNA expression in patients with
      hepatocellular carcinoma.
AB  - Enhancer of zeste homologue 2 (EZH2), a member of the polycomb group protein
      family, plays a crucial role in the regulation of embryonic development and has
      been associated with the regulation of the cell cycle. Recently, several studies
      have shown that EZH2 is highly expressed in aggressive tumours, including human
      breast cancer, prostate cancer, and lymphomas. We thus analysed EZH2 expression
      using real-time reverse transcription-polymerase chain reaction, and correlated
      its expression status with various clinicopathological parameters in 66 patients
      with hepatocellular carcinoma (HCC). We found high expression of EZH2 in human
      liver cancer cell lines. Furthermore, EZH2 gene-expression levels in tumour
      tissue specimens (0.34+/-0.52) were significantly higher (P<0.0001) than those in
      the corresponding nontumour tissue specimens (0.07+/-0.09). The incidence of
      cancer cell invasion into the portal vein was significantly higher (P<0.001) in
      the high EZH2 expression group (26 of the 33, 79%) than in the low expression
      group (13 of the 33, 39%). However, there was no significant difference in the
      disease-free survival rate between the two groups. The findings of this study
      indicate that EZH2 mRNA expression was upregulated in human HCC and may play an
      important role in tumour progression, especially by facilitating portal vein
      invasion.

PMID- 15856047
TI  - Enhanced expression of type I interferon and toll-like receptor-3 in primary
      biliary cirrhosis.
AB  - The pathogenesis of primary biliary cirrhosis (PBC) remains enigmatic. In order
      to address this issue, we analyzed by laser capture microdissection and real-time
      reverse transcription-polymerase chain reaction the site-specific expression of
      messenger RNA (mRNA) for cytokines (interferon (IFN)-alpha, -beta, -gamma,
      interleukin (IL)-1beta, -4, -6, -10, -12p40, -18, tumor necrosis factor-alpha)
      and toll-like receptors (TLRs) (TLR-2, -3, -4, -7, -9) in portal tract and liver
      parenchyma from patients with early-stage PBC. Expression of IFN-alpha, -beta and
      TLR-3 proteins was also studied by immunohistochemistry. Autoimmune hepatitis
      (AIH) and chronic hepatitis C (CHC) served as disease controls. The expression
      levels of type I IFN (IFN-alpha, -beta) and TLR-3 mRNAs, which are known to
      induce type I IFN, were significantly higher in portal tract and liver parenchyma
      as compared to AIH and CHC. A strong positive correlation between the mRNA levels
      of type I IFN and TLR-3 was also seen in both areas. Immunohistologically, IFN
      alpha is present in the mononuclear cells in portal tract and sinusoidal cells.
      Macrophages in portal tract and hepatocytes expressed IFN-beta and TLR-3.
      Furthermore, the level of IFN-alpha mRNA in the portal tract was positively
      correlated with serum alkaline phosphatase. In conclusion, these data indicate
      that TLR-3 and type I IFN signaling pathways are active in both the portal tract
      and liver parenchyma of early-stage PBC, and form the basis for our hypothesis
      that these signaling pathways are involved in the pathophysiology of PBC.

PMID- 15856048
TI  - Local overexpression of HB-EGF exacerbates remodeling following myocardial
      infarction by activating noncardiomyocytes.
AB  - Insulin-like growth factor (IGF), hepatocyte growth factor (HGF), and heparin
      binding epidermal growth factor-like growth factor (HB-EGF) are cardiogenic and
      cardiohypertrophic growth factors. Although the therapeutic effects of IGF and
      HGF have been well demonstrated in injured hearts, it is uncertain whether
      natural upregulation of HB-EGF after myocardial infarction (MI) plays a
      beneficial or pathological role in the process of remodeling. To answer this
      question, we conducted adenoviral HB-EGF gene transduction in in vitro and in
      vivo injured heart models, allowing us to highlight and explore the HB-EGF
      induced phenotypes. Overexpressed HB-EGF had no cytoprotective or additive death
      inducible effect on Fas-induced apoptosis or oxidative stress injury in primary
      cultured mouse cardiomyocytes, although it significantly induced hypertrophy of
      cardiomyocytes and proliferation of cardiac fibroblasts. Locally overexpressed HB
      EGF in the MI border area in rabbit hearts did not improve cardiac function or
      exhibit an angiogenic effect, and instead exacerbated remodeling at the subacute
      and chronic stages post-MI. Namely, it elevated the levels of apoptosis,
      fibrosis, and the accumulation of myofibroblasts and macrophages in the MI area,
      in addition to inducing left ventricular hypertrophy. Thus, upregulated HB-EGF
      plays a pathophysiological role in injured hearts in contrast to the therapeutic
      roles of IGF and HGF. These results imply that regulation of HB-EGF may be a
      therapeutic target for treating cardiac hypertrophy and fibrosis.

PMID- 15856049
TI  - Differential expression of pro- and antiangiogenic factors in mouse strain
      dependent hypoxia-induced retinal neovascularization.
AB  - Clinical observations suggest that genetic factors may influence heterogeneity of
      angiogenic responses in cardiovascular disease, proliferative diabetic
      retinopathy, and neoplasia. Experiments among mouse strains using a corneal
      micropocket assay indicate that extent of angiogenesis may be genetically
      determined. Here, we established the strain-dependence of hypoxia-induced retinal
      angiogenesis in multiple mouse strains which paralleled the rank order found for
      bFGF-induced corneal angiogenesis. Using quantitative real-time RT-PCR, strain
      related gene expression differences in retina/choroid between C57BL/6J and
      129S3/SvIM, inbred strains with relatively low and high levels of angiogenesis,
      respectively, after 0, 6, 12, 24, 48, and 96 h hypoxia were determined for
      vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), angiogenic
      ligands potently induced by hypoxia, and for pigment epithelium-derived factor
      (PEDF) and thrombospondin-1 (TSP-1), endogenous broad-spectrum antiangiogenic
      factors. Indirect ELISA was used to correlate VEGF and PEDF protein levels with
      mRNA expression. At the onset of hypoxia, both PEDF and TSP-1 levels were
      increased over 15-fold and VEGF was increased over 10-fold compared to Ang-2 in
      both strains. At the onset of neovascularization (48 h), both VEGF and Ang-2 mRNA
      levels were increased in the more angiogenic 129S3/SvIM strain (P < 0.02), which
      was not observed among developmental control animals. PEDF expression was higher
      in the less angiogenic C57BL/6J strain at 6, 12, 24, and 96 h hypoxia (P < 0.03),
      while TSP-1 expression was higher in C57BL/6J throughout the entire time course
      of hypoxia (4 days) compared to 129S3/SvIM (P < 0.02). Among developmental
      control animals, PEDF and TSP-1 expression was also increased at P14 and P16 in
      C57BL/6J strain compared to 129S3/SvIM (P < 0.02). Strain-dependent expression of
      both pro- and antiangiogenic growth factors may determine heterogeneity in the
      angiogenic response and potentially, susceptibility to angiogenesis-dependent
      diseases.

PMID- 15856050
TI  - The perils of public debate.

PMID- 15856051
TI  - Is prefrontal white matter enlargement a human evolutionary specialization?

PMID- 15856054
TI  - Imaging orientation selectivity: decoding conscious perception in V1.

PMID- 15856055
TI  - Finding the G spot on fusion machinery.

PMID- 15856056
TI  - Axon formation: fate versus growth.

PMID- 15856057
TI  - Song learning and sleep.

PMID- 15856058
TI  - Trafficking in emotions.

PMID- 15856059
TI  - SK channels: a new twist to synaptic plasticity.

PMID- 15856060
TI  - Neurobiology of obesity.

PMID- 15856061
TI  - Obesity on the brain.

PMID- 15856062
TI  - How can drug addiction help us understand obesity?

PMID- 15856063
TI  - The hardship of obesity: a soft-wired hypothalamus.
AB  - Food intake and energy expenditure are determinants of metabolic phenotype and
      are regulated by the CNS. Although humans have a well-balanced homeostatic
      feedback loop, obesity and metabolic disorders are spreading rapidly and carry a
      heavy toll of morbidity and mortality. The past decade has witnessed major
      advances in the understanding of basic metabolic processes, the brain circuitry
      that determines appropriate and, but, inappropriate behavioral and humoral
      responses to changing metabolic cues remains largely ill defined. This review
      summarizes current knowledge of the brain anatomy that supports food intake and
      energy expenditure and discusses cellular mechanisms such as synaptic plasticity
      that may provide clues toward the development of successful central therapies to
      combat metabolic disorders, including obesity and diabetes.

PMID- 15856064
TI  - Molecular and anatomical determinants of central leptin resistance.
AB  - The increasing incidence of obesity in developed nations is an ever-growing
      challenge to health care, promoting diabetes and other diseases. The hormone
      leptin, which is derived from adipose tissue, regulates feeding and energy
      expenditure. Most forms of obesity are associated with diminished responsiveness
      to the appetite-suppressing effects of leptin. Here we review the mechanisms by
      which leptin activates intracellular signals, the roles of these signals in
      leptin action in vivo, and mechanisms that may attenuate leptin signaling,
      limiting its action in obese individuals. We highlight data regarding the
      expression of SOCS3 (a potential mediator of leptin resistance) in the arcuate
      nucleus of the hypothalamus.

PMID- 15856065
TI  - Anatomy and regulation of the central melanocortin system.
AB  - The central melanocortin system is perhaps the best-characterized neuronal
      pathway involved in the regulation of energy homeostasis. This collection of
      circuits is unique in having the capability of sensing signals from a staggering
      array of hormones, nutrients and afferent neural inputs. It is likely to be
      involved in integrating long-term adipostatic signals from leptin and insulin,
      primarily received by the hypothalamus, with acute signals regulating hunger and
      satiety, primarily received by the brainstem. The system is also unique from a
      regulatory point of view in that it is composed of fibers expressing both
      agonists and antagonists of melanocortin receptors. Given that the central
      melanocortin system is an active target for development of drugs for the
      treatment of obesity, diabetes and cachexia, it is important to understand the
      system in its full complexity, including the likelihood that the system also
      regulates the cardiovascular and reproductive systems.

PMID- 15856066
TI  - Hypothalamic sensing of fatty acids.
AB  - Selective regions of the brain, including the hypothalamus, are capable of
      gathering information on the body's nutritional status in order to implement
      appropriate behavioral and metabolic responses to changes in fuel availability.
      This review focuses on direct metabolic signaling within the hypothalamus. There
      is growing evidence supporting the idea that fatty acid metabolism within
      discrete hypothalamic regions can function as a sensor for nutrient availability
      that can integrate multiple nutritional and hormonal signals.

PMID- 15856067
TI  - Endocannabinoid control of food intake and energy balance.
AB  - Marijuana and its major psychotropic component, Delta(9)-tetrahydrocannabinol,
      stimulate appetite and increase body weight in wasting syndromes, suggesting that
      the CB(1) cannabinoid receptor and its endogenous ligands, the endocannabinoids,
      are involved in controlling energy balance. The endocannabinoid system controls
      food intake via both central and peripheral mechanisms, and it may also stimulate
      lipogenesis and fat accumulation. Here we discuss the multifaceted regulation of
      energy homeostasis by endocannabinoids, together with its applications to the
      treatment of eating disorders and metabolic syndromes.

PMID- 15856068
TI  - Phytosterols in nonfat and low-fat beverages have no impact on the LDL size
      phenotype.
AB  - OBJECTIVE: To examine the impact of nonfat and low-fat phytosterol-enriched
      beverages on low-density lipoprotein (LDL) electrophoretic characteristics.
      DESIGN: Double-blind, randomized, crossover, placebo-controlled dietary trial.
      SETTING: Diets were prepared and consumed at the Mary Emily Clinical Nutrition
      Research Unit of McGill University. Analyses were performed at the Institute on
      Nutraceuticals and Functional Foods of Laval University. SUBJECTS AND
      INTERVENTION: In total, 15 moderately hypercholesterolemic persons consumed each
      of three experimental diets that each comprised a different beverage: nonfat
      placebo (NF control), nonfat with phytosterols (NFPS) or low-fat with
      phytosterols (LFPS). Participants consumed three beverages daily at meal time for
      a total of 1.8 g of phytosterols per day. Nondenaturing 2-16% polyacrylamide
      gradient gel electrophoreses were used to characterize LDL size characteristics.
      RESULTS: The NFPS and LFPS beverage induced no significant changes in several
      features of the LDL size phenotype compared to the control diet. CONCLUSION: The
      consumption of phytosterol-supplemented nonfat and low-fat beverages is not
      associated with clinically meaningful changes in the LDL particle size phenotype.

PMID- 15856069
TI  - A new vision for age-related macular degeneration.

PMID- 15856070
TI  - TaqIB polymorphism in CETP gene: the influence on incidence of cardiovascular
      disease in statin-treated patients with familial hypercholesterolemia.
AB  - The effects of TaqI restriction fragment length polymorphism of the CETP gene on
      the occurrence of cardiovascular disease (CVD) events were investigated in
      patients with familial hypercholesterolemia (FH). A total of 300 FH patients, of
      which 116 (39%) had CVD at the start of the study, were treated with statins
      during a mean period of 8.5 years. The distribution of Taq1B genotypes was 31%
      B1B1, 49% B1B2, and 20% B2B2. No differences were found at baseline between the
      three genotypes, except for an association of the B1 allele with lower high
      density lipoprotein (HDL)-cholesterol levels (P=0.003). All patients were put on
      statins within 6-8 weeks after the first visit; about 60% received simvastatin
      (20-40 mg daily) and 40% either pravastatin (40 mg daily) or atorvastatin (20-40
      mg daily). The different statin treatments were similar for all groups. The mean
      change of plasma HDL-cholesterol, low-density lipoprotein-cholesterol, and
      triglyceride concentration during statin therapy was similar for the three
      genotypes. During follow-up, new CVD events were recorded in 22 (37%) of the B2B2
      patients (n=59) and in 67 (28%) of B1 allele carriers (n=241) (P=0.36). The
      relative risk for CVD events, after adjustment for age, gender, and CVD at
      intake, was 1.8 (CI: 1.1-3.0) for B2B2 carriers compared to B1 allele carriers.
      The Taq1B polymorphism is a significant predictor of future CVD events in statin
      treated patients with FH. In spite of similar improvement of the lipoprotein
      profile during statin therapy, our FH patients with the B2B2 genotype may have a
      higher CVD risk in comparison with the B1 allele carriers.

PMID- 15856071
TI  - An investigation of NOS2A promoter polymorphisms in Australian multiple sclerosis
      patients.
AB  - As with other major autoimmune diseases, susceptibility to multiple sclerosis
      (MS) is believed to result from the complex interaction of a number of genes,
      each with modest effect. Extensive research of experimental autoimmune
      encephalomyelitis in mice and several direct MS studies have implicated NOS2A,
      which encodes the inducible form of nitric oxide synthase, and the genetic region
      encoding NOS2A, 17q11.2, has been identified in a number of genome wide screens
      as being potentially associated with MS. We investigated four single nucleotide
      polymorphisms in the proximal promoter region of NOS2A, in a case-control group
      of 100 Australian MS patients and 100 controls and in 203 MS patients and their
      unaffected parents. We found a trend toward excess transmission of the -277A
      allele (tag for the AGCC haplotype) to HLA-DRB1*1501-positive MS patients (P
      (uncorrected)=0.05). We initially discovered a trend toward over-representation
      of the AGCC haplotype in HLA-DRB1*1501-positive compared to HLA-DRB1*1501
      negative MS patients in the case-control cohort. However, when combined with the
      probands from the transmission disequilibrium analysis, this trend was nullified.
      Nonetheless, despite the lack of significant evidence of association for the
      NOS2A promoter polymorphisms with MS, the gene remains an interesting candidate
      for MS susceptibility, particularly with regard to the HLA-DRB1*1501 haplotype.

PMID- 15856072
TI  - Childhood overgrowth in patients with common NF1 microdeletions.
AB  - While growth retardation and short stature are well-known features of patients
      with classical neurofibromatosis type 1 (NF1), we found advanced height growth
      and accelerated carpal bone age in patients with an NF1 microdeletion. Our
      analysis is based on growth data of 21 patients with common 1.4/1.2 Mb
      microdeletions, including three patients with a Weaver-like appearance.
      Overgrowth was most evident in preschool children (2-6 years, n=10, P=0.02). We
      conclude that childhood overgrowth is part of the phenotypic spectrum in patients
      with the common 1.4/1.2 Mb NF1 microdeletions and assume that the chromosomal
      region comprised by the microdeletions contains a gene whose haploinsufficiency
      causes overgrowth.

PMID- 15856073
TI  - Contrasting patterns of Y chromosome and mtDNA variation in Africa: evidence for
      sex-biased demographic processes.
AB  - To investigate associations between genetic, linguistic, and geographic variation
      in Africa, we type 50 Y chromosome SNPs in 1122 individuals from 40 populations
      representing African geographic and linguistic diversity. We compare these
      patterns of variation with those that emerge from a similar analysis of published
      mtDNA HVS1 sequences from 1918 individuals from 39 African populations. For the Y
      chromosome, Mantel tests reveal a strong partial correlation between genetic and
      linguistic distances (r=0.33, P=0.001) and no correlation between genetic and
      geographic distances (r=-0.08, P>0.10). In contrast, mtDNA variation is weakly
      correlated with both language (r=0.16, P=0.046) and geography (r=0.17, P=0.035).
      AMOVA indicates that the amount of paternal among-group variation is much higher
      when populations are grouped by linguistics (Phi(CT)=0.21) than by geography
      (Phi(CT)=0.06). Levels of maternal genetic among-group variation are low for both
      linguistics and geography (Phi(CT)=0.03 and 0.04, respectively). When Bantu
      speakers are removed from these analyses, the correlation with linguistic
      variation disappears for the Y chromosome and strengthens for mtDNA. These data
      suggest that patterns of differentiation and gene flow in Africa have differed
      for men and women in the recent evolutionary past. We infer that sex-biased rates
      of admixture and/or language borrowing between expanding Bantu farmers and local
      hunter-gatherers played an important role in influencing patterns of genetic
      variation during the spread of African agriculture in the last 4000 years.

PMID- 15856075
TI  - A conceptual framework for modeling aggregate and cumulative exposures to
      chemicals.
AB  - Computer simulation programs have been identified as useful tools for
      characterizing uncertainty and variability in longitudinal exposures to multiple
      sources by multiple routes of exposures. This paper provides a conceptual
      framework for such programs that separates and appropriately models the processes
      that determine uncertainty, inter- and intraindividual variability, as well as
      the processes that determine the relationships between the individuals and
      sources of exposure. The framework is based on a series of four nested loops.
      These are: the exposure event loop that models the route-specific doses to a
      person from one or more sources at one point in time; the time step loop that
      moves a person through time updating the sources and the person's
      characteristics, the interindividual variation loop that determines the initial
      characteristics of each person modeled, and finally the uncertainty loop that
      characterizes the uncertainty from model and parameter uncertainties. This
      framework provides a flexible and internally consistent approach for the design
      of simulation software.

PMID- 15856074
TI  - Residential environmental exposures and other characteristics associated with
      detectable PAH-DNA adducts in peripheral mononuclear cells in a population-based
      sample of adult females.
AB  - The detection of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human
      lymphocytes may be useful as a surrogate end point for individual cancer risk
      prediction. In this study, we examined the relationship between environmental
      sources of residential PAH, as well as other potential factors that may confound
      their association with cancer risk, and the detection of PAH-DNA adducts in a
      large population-based sample of adult women. Adult female residents of Long
      Island, New York, aged at least 20 years were identified from the general
      population between August 1996 and July 1997. Among 1556 women who completed a
      structured questionnaire, 941 donated sufficient blood (25+ ml) to allow use of a
      competitive ELISA for measurement of PAH-DNA adducts in peripheral blood
      mononuclear cells. Ambient PAH exposure at the current residence was estimated
      using geographic modeling (n=796). Environmental home samples of dust (n=356) and
      soil (n=360) were collected on a random subset of long-term residents (15+
      years). Multivariable regression was conducted to obtain the best-fitting
      predictive models. Three separate models were constructed based on data from :
      (A) the questionnaire, including a dietary history; (B) environmental home
      samples; and (C) geographic modeling. Women who donated blood in summer and fall
      had increased odds of detectable PAH-DNA adducts (OR=2.65, 95% confidence
      interval (CI)=1.69, 4.17; OR=1.59, 95% CI=1.08, 2.32, respectively), as did
      current and past smokers (OR=1.50, 95% CI=1.00, 2.24; OR=1.46, 95% CI=1.05, 2.02,
      respectively). There were inconsistent associations between detectable PAH-DNA
      adducts and other known sources of residential PAH, such as grilled and smoked
      foods, or a summary measure of total dietary benzo-[a]-pyrene (BaP) intake during
      the year prior to the interview. Detectable PAH-DNA adducts were inversely
      associated with increased BaP levels in dust in the home, but positively
      associated with BaP levels in soil outside of the home, although CIs were wide.
      Ambient BaP estimates from the geographic model were not associated with
      detectable PAH-DNA adducts. These data suggest that PAH-DNA adducts detected in a
      population-based sample of adult women with ambient exposure levels reflect some
      key residential PAH exposure sources assessed in this study, such as cigarette
      smoking.

PMID- 15856076
TI  - Probing for affective side effects of drugs used in geriatric practice: use of
      daily diaries to test for effects of metoclopramide and naproxen.
AB  - The aim of this study was to develop the use of daily diaries of affects and
      events as measures of pharmacological effects on affective processes and to apply
      them to evaluate the possible affective toxicity of metoclopramide and naproxen,
      two medications commonly used in geriatric practice. In all, 105 adults aged 65
      years or older were randomized to receive metoclopramide (up to 40 mg/day),
      naproxen (up to 1000 mg/day), or placebo under double-blind conditions for a
      period of 5 weeks. Patients were seen weekly for evaluations of affective and
      cognitive outcomes as well as safety. In addition, patients kept diaries with
      daily records of positive and negative affect and reports of significant daily
      events. Findings included mixed model analyses of drug assignment, time, events,
      and interactions for both positive affect and days with significant negative
      affect. Subjects exhibited high levels of adherence in completing daily diaries.
      Neither the pattern of dropouts nor the weekly assessments demonstrated
      significant drug effects on mood or affect. However, diary data demonstrated that
      metoclopramide increased the apparent impact of negative events on both positive
      and negative affect relative to placebo, and that naproxen increased the apparent
      impact of positive events on positive affect and, possibly, of negative events on
      negative affect relative to placebo. The findings confirm the utility of diary
      methods for studying drug effects on affective processes in normal elderly
      subjects. They suggest that both metoclopramide and naproxen can affect the
      associations between daily events and affects. If replicated, they would
      demonstrate that drug effects can extend beyond the intensity of affect and/or
      the emergence of full-fledged psychiatric disorders to include moderation of the
      interactions between daily events and affect.

PMID- 15856077
TI  - A conceptualization of integrated actions of ethanol contributing to its
      GABAmimetic profile: a commentary.
AB  - Early behavioral investigations supported the contention that systemic ethanol
      displays a GABAmimetic profile. Microinjection of GABA agonists into brain and in
      vivo electrophysiological studies implicated a regionally specific action of
      ethanol on GABA function. While selectivity of ethanol to enhance the effect of
      GABA was initially attributed an effect on type-I-benzodiazepine (BZD)-GABA(A)
      receptors, a lack of ethanol's effect on GABA responsiveness from isolated
      neurons with this receptor subtype discounted this contention. Nonetheless,
      subsequent work identified GABA(A) receptor subtypes, with limited distribution
      in brain, sensitive to enhancement of GABA at relevant ethanol concentrations. In
      view of these data, it is hypothesized that the GABAmimetic profile for ethanol
      is due to activation of mechanisms associated with GABA function, distinct from a
      direct action on the majority of postsynaptic GABA(A) receptors. The primary
      action proposed to account for ethanol's regional specificity on GABA
      transmission is its ability to release GABA from some, but not all, presynaptic
      GABAergic terminals. As systemic administration of ethanol increases neuroactive
      steroids, which can enhance GABA responsiveness, this elevated level of
      neurosteroids is proposed to magnify the effect of GABA released by ethanol.
      Additional factors contributing to the degree to which ethanol interacts with
      GABA function include an involvement of GABA(B) and other receptors that
      influence ethanol-induced GABA release, an effect of phosphorylation on GABA
      responsiveness, and a regional reduction of glutamatergic tone. Thus, an
      integration of these consequences induced by ethanol is proposed to provide a
      logical basis for its in vivo GABAmimetic profile.

PMID- 15856078
TI  - Abstinence from cocaine self-administration heightens neural encoding of goal
      directed behaviors in the accumbens.
AB  - Cocaine addiction in humans is characterized by cycles of abstinence from drug
      taking and relapse. Here, electrophysiological recording procedures were used to
      determine whether nucleus accumbens (Acb) neuronal firing properties are altered
      following interruption and resumption of cocaine self-administration. Rats (n =
      12) were trained to self-administer cocaine (2 h daily sessions) then divided
      into two groups. Acb activity was recorded for Group 1 (controls) during two
      additional self-administration sessions completed over the next 2 days (test
      sessions 1 and 2). Acb activity was recorded for Group 2 (1-month) during one
      self-administration session completed the next day (test 1), and during a second
      self-administration session 1 month later (test 2). As in prior reports, a subset
      of Acb neurons exhibited patterned discharges (short duration and/or long-term
      cyclic alterations, termed 'phasically active') relative to cocaine-reinforced
      responding during test session 1. Remarkably, the percentage of phasically active
      cells dramatically increased (nearly two-fold) following 1-month abstinence, in
      the core but not the shell of the Acb. Likewise, the strength of the neural
      correlates (determined via signal-to-baseline ratios) also increased as a
      function of abstinence. Extinction experiments in another set of rats (n = 12)
      revealed an increased motivational state for the drug following abstinence. The
      results show that abstinence from cocaine self-administration causes a dramatic
      increase in the number and strength of Acb neurons that encode cocaine-related
      information, thus representing the first neurophysiological correlate of
      heightened activation of the 'brain reward system' following abstinence and
      resumption (relapse) of cocaine consumption.

PMID- 15856079
TI  - Treatment enhances ultradian rhythms of CSF monoamine metabolites in patients
      with major depressive episodes.
AB  - Unipolar and bipolar depressions show abnormal behavioral manifestations of
      ultradian (less than 24 h) rhythms, but abnormal rhythms of the central
      neurotransmitters thought to be important for depression pathophysiology (eg
      dopamine (DA) and serotonin (5-HT)) have not been shown in this time frame. Since
      antidepressant treatments normalize disrupted rhythms in depression (eg rapid-eye
      movement sleep and hormonal rhythms), we hypothesized that depression-related
      changes in ultradian oscillations of DA and 5-HT might be revealed during
      antidepressant treatment. Cerebrospinal fluid (CSF) samples collected q10 min for
      24 h in 13 patients experiencing major depressive episodes (MDE) before and after
      treatment for 5 weeks with sertraline or bupropion were assayed for levels of
      homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), and their ratio
      was calculated. Data were analyzed in the frequency domain using Fourier
      transforms and multivariate permutation testing. Antidepressant treatments were
      associated with decreased variance for 5-HIAA, increased variance for HVA, and
      markedly increased variance for the HVA : 5-HIAA ratio (p<0.05, p<0.02, and
      p<0.003, respectively). With treatment, the correlations between 5-HIAA and HVA
      weakened (p=0.06). Power spectral density (PSD-the Fourier magnitude squared) of
      the 5-HIAA signals at periods of 1.75 and 3.7 h (both p<0.05) decreased, while
      circadian cycling of HVA levels (p<0.05) and of the ratio (p<0.005) increased
      after treatment. The PSD of the full-length HVA : 5-HIAA ratio series after
      treatment increased in rapid variability (20-103 min periods, p<0.05).
      Spectrographic windowing demonstrated a focal span of enhanced HVA : 5-HIAA ratio
      variability following antidepressant treatment, in an approximately 84-min period
      through the evening (p<0.05). Periodic neurotransmitter relationships in
      depressed patients were altered by treatment in this analysis of a small data
      set. This may represent a baseline abnormality in the regulation of periodic
      functions involved in the depression pathophysiology, but it could also be due to
      an unrelated antidepressant effect. Further studies including comparisons with
      healthy subject data are in progress.

PMID- 15856080
TI  - Nicotine normalizes increased prefrontal cortical dopamine D1 receptor binding
      and decreased working memory performance produced by repeated pretreatment with
      MK-801: a PET study in conscious monkeys.
AB  - The effects of acute nicotine were determined on dopamine (DA) D(1) (D(1)R) and
      D(2) (D(2)R) receptor binding in the neocortex of conscious monkeys under control
      conditions as well as after chronic pretreatment with MK-801 (dizocilpine), a
      noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Extrastriatal
      neocortical D(1)R and D(2)R binding was evaluated with [(11)C]NNC112 and
      [(11)C]FLB457 with high-specific radioactivity using positron emission tomography
      (PET). Acute administration of nicotine bitartrate, given as an intravenous
      (i.v.) bolus plus infusion for 30 min at doses of 32 microg/kg+0.8 microg/kg/min
      or 100 microg/kg+2.53 microg/kg/min as base, induced slight but significant dose
      dependent increases of DA in the extracellular fluid of prefrontal cortex (PFC)
      as determined by microdialysis. However, acute nicotine did not affect either
      [(11)C]NNC112 or [(11)C]FLB457 binding to D(1)R or D(2)R, respectively, in any
      cortical region. Chronic MK-801 (0.03 mg/kg, intramuscularly (i.m.), twice daily
      for 13 days) increased [(11)C]NNC112 binding to D(1)R in PFC. No significant
      changes were detected in [(11)C]FLB457 binding to PFC D(2)R. Although chronic MK
      801 lowered baseline DA and glutamate levels in PFC, acute nicotine normalized
      reduced DA to control levels. Acute nicotine dose-dependently normalized the
      increased binding of [(11)C]NNC112 to D(1)R produced by chronic MK-801 but
      [(11)C]FLB457 binding to PFC D(2)R did not change. Working memory performance,
      impaired after chronic MK-801, was partially improved by acute nicotine. These
      results demonstrate that acute nicotine normalizes MK-801-induced PFC abnormality
      of D(1)R in PFC.

PMID- 15856081
TI  - Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI
      study.
AB  - The mechanisms by which antidepressant-induced neurochemical changes lead to
      physiological changes in brain circuitry and ultimately an antidepressant
      response remain unclear. This study investigated the effects of sertraline, a
      selective serotonin reuptake inhibitor antidepressant, on corticolimbic
      connectivity, using functional magnetic resonance imaging (fMRI). In all, 12
      unmedicated unipolar depressed patients and 11 closely matched healthy control
      subjects completed two fMRI scanning sessions at baseline and after 6 weeks.
      Depressed patients received treatment with sertraline between the two sessions.
      During each fMRI session, subjects first completed a conventional block-design
      experiment. Next, connectivity between cortical and limbic regions was measured
      using correlations of low-frequency blood oxygen level-dependent (BOLD)
      fluctuations (LFBF) during continuous exposure to neutral, positive, and negative
      pictures. At baseline, depressed patients had decreased corticolimbic LFBF
      correlations compared to healthy subjects during the resting state and on
      exposure to emotionally valenced pictures. At rest and on exposure to neutral and
      positive pictures, LFBF correlation between the anterior cingulate cortex and
      limbic regions was significantly increased in patients after treatment. However,
      on exposure to negative pictures, corticolimbic LFBF correlations remained
      decreased in depressed patients. The results of this study are consistent with
      the hypothesis that antidepressant treatment may increase corticolimbic
      connectivity, thereby possibly increasing the regulatory influence of cortical
      mood-regulating regions over limbic regions.

PMID- 15856082
TI  - Novelty seeking and stereotypic activation of behavior in mice with disruption of
      the Dat1 gene.
AB  - Disruption of the dopamine (DA) transporter (Dat1) gene in mice leads to a 50%
      reduction or complete elimination of Dat1 expression in striatum of respective
      heterozygous (HZ) and knockout (KO) mice. Compared to wild-type (WT) controls,
      extracellular DA is increased approximately two- and five-fold in the mutants.
      Although open field (OF) activity is similar for WT and HZ animals, it is
      enhanced for KO mice. The purpose of the present investigations was to study
      spontaneously emitted behaviors and to determine the behavioral and neurochemical
      mechanisms that may contribute to the hyperactivity of KO animals. Heterozygotes
      are less anxious than other genotypes and they engage in novelty-seeking
      behaviors that include increased time spent in the center of the OF, enhanced
      investigation of objects, and augmented free exploration of a novel environment.
      By comparison, KO mice display neophobia when initially exposed to novel
      conditions. Over time the anxiety-like response habituates and behaviors become
      activated and stereotyped; these responses are unrelated to exploration or
      novelty seeking. No alterations in extracellular DA levels or tissue contents
      from several brain regions are detected at the time of stereotypic activation of
      KO mice. By contrast, this behavior is accompanied by changes in serotonin
      metabolism in basal ganglia. This feature may contribute to the behavioral
      inflexibility of KO mice in different experimental contexts. Collectively, these
      findings suggest that disruption of the Dat1 gene in mice leads to two different
      phenotypes; one related to anxiety-reducing and novelty seeking, while the other
      has some homology to disorders with a stereotypical-perseverative spectrum.

PMID- 15856084
TI  - Technologies for nanofluidic systems: top-down vs. bottom-up--a review.
AB  - This paper gives an overview of the most commonly used techniques for
      nanostructuring and nanochannel fabrication employed in nanofluidics. They are
      divided into two large categories: top-down and bottom-up methods. Top-down
      methods are based on patterning on large scale while reducing the lateral
      dimensions to the nanoscale. Bottom-up methods arrange atoms and molecules in
      nanostructures. Here, we review the advantages and disadvantages of those methods
      and give some future perspectives. It is concluded that technology in the region
      of 1-10 nm is lacking and potentially can be covered by using the pulsed-laser
      deposition method as a controlled way for thin film deposition (thickness of a
      few nanometers) and further structuring by the top-down method.

PMID- 15856085
TI  - Planar thin film device for capillary electrophoresis.
AB  - Hollow tubular microfluidic channels were fabricated on quartz substrates using
      sacrificial layer, planar micromachining processes. The channels were created
      using a bottom-up fabrication technique, namely patterning a photoresist/aluminum
      sacrificial layer and depositing SiO(2) over the substrate. The
      photoresist/aluminum layer was removed by etching first with HCl/HNO(3), followed
      by etching in Nano-Strip, a more stable form of piranha (H(2)SO(4)/H(2)O(2))
      stripper. Rapid separation of fluorescently labeled amino acids was performed on
      a device made with these channels. The fabrication process presented here
      provides unique control over channel composition and geometry. Future work should
      allow the fabrication of highly complex and precise devices with integrated
      analytical capabilities essential for the development of micro-total analysis
      systems.

PMID- 15856086
TI  - Optimization of poly(dimethylsiloxane) hollow prisms for optical sensing.
AB  - A new generation of simple, robust and compact microfluidic systems with optical
      readout is presented. The devices consist of hollow prisms fabricated by soft
      lithography, together with microlenses and self-aligned channels for fibre optic
      positioning, conferring the system with a high degree of monolithic integration.
      Its working principle is based on the absorption of the working wavelength
      (lambda = 460 nm) by the different substances that can fill the hollow prisms. By
      modifying the volumes and geometries, optimization of the presented systems has
      been achieved. Results show how the limit of detection (LOD) for fluorescein and
      methylorange diluted in phosphate buffer can be significantly lowered, by
      increasing the size of the prism or increasing the total deviation angle. For our
      investigations we used concentrations for which the Beer-Lambert law is fulfilled
      and the measurements showed a LOD in the microM range for both species. Finally,
      since the change in the fractions of the methylorange as a function of the pH
      causes a variation of the total absorption of the solution, the hollow prisms
      have also been used for pH measurements.

PMID- 15856087
TI  - Large area UV casting using diverse polyacrylates of microchannels separated by
      high aspect ratio microwalls.
AB  - Large area molding of long and deep microchannels separated by high aspect ratio
      microwalls is important for high sensitivity and high throughput microfluidic
      devices. Ultraviolet (UV) casting is a feasible, economical and convenient method
      of replication of such microstructures in plastics. It is shown that a wide
      variety of polyacrylates with diverse properties such as those made from epoxy
      (EP), polyurethane (UR), polyester (ES), poly (ethylene glycol) (EG) and
      poly(propylene glycol) (PG) can be used for the high aspect ratio (7-9) UV
      casting of such linear microstructures over a 100 mm diameter, enlarging the
      range of applications of the replicated microstructures. Some challenges arise.
      With the EG formulation, wavy microstructures were observed; this can be overcome
      by stress relaxation. With non-polar PG formulation, poor adhesion between the
      polyester substrate and resin can lead to delamination of the casting from the
      substrate during demolding; this can be overcome by pre-coating a partially cured
      same resin on the polyester substrate. An optimum UV irradiation time was
      important for cure at the deepest end of the microstructure without excessive
      crosslinking leading to much increased demolding forces. The viscosity and
      wetting capability of the formulations were found to affect replication fidelity.

PMID- 15856088
TI  - Parylene flexible neural probes integrated with microfluidic channels.
AB  - The fluidic channel in the flexible probe has three functions: (i) to inject
      chemicals into the tissues, (ii) to measure the neural activities from the
      tissues, and (iii) to improve the mechanical stiffness of the probe by filling
      the channel with a solid material. A 10-microm-thick microfluidic channel was
      embedded into the probe by using sacrificial photoresist patterns. Polyethylene
      glycol (PEG), which is solid at room temperature and dissolves when in contact
      with water, was used to fill the channel and increase the stiffness of the probe
      before insertion into the tissue. The impedance of the electrode inside the
      fluidic channel was around 100 kOmega at 1 kHz when the channel was filled with
      saline solution. We were able to insert the probe into a rat's brain and measure
      the neural signals with the electrode.

PMID- 15856089
TI  - A microfluidic mixer with grooves placed on the top and bottom of the channel.
AB  - A new microfluidic mixer is presented consisting of a rectangular channel with
      grooves placed in the top and bottom. This not only increases the driving force
      behind the lateral flow, but allows for the formation of advection patterns that
      cannot be created with structures on the bottom alone. Chevrons, pointing in
      opposite directions on the top and bottom, are used to create a pair of vortices
      positioned side by side. Stripes running the width of the channel generate a pair
      of vertically stacked vortices. Computational fluid dynamics (CFD) simulations
      are used to model the behavior of the systems and provide velocity maps at cross
      sections within the mixer. Experiments demonstrate the mixing that results when
      two segregated species enter the mixer side-by-side and pass through two cycles
      of the mixer (i.e., two alternating sets of four stripes and four chevrons).

PMID- 15856090
TI  - Surfactant-enhanced liquid-liquid extraction in microfluidic channels with inline
      electric-field enhanced coalescence.
AB  - Continuous microfluidic liquid-liquid extraction is realized in a microfluidic
      device by generating emulsions with large interfacial areas for mass transfer,
      and subsequently breaking these emulsions using electric fields into easily
      separated segments of immiscible liquids (plugs). The microfluidic device employs
      insulated electrodes in a potassium hydroxide-etched channel to create large
      electric fields (100 kV m(-1)) that drive coalescence of the emulsion phase. The
      result is a transition from disperse to slug flow that can then readily be
      separated by gravity. Extractions of phenol and p-nitrophenol from an aqueous to
      hexane-surfactant solution serve as model systems. In addition to the increased
      surface area in the emulsion, extraction efficiency is enhanced by reverse
      micelles resulting from the presence of surfactants. The surfactant concentration
      is varied approximately 1-10 wt% and a general two-parameter model is developed
      to quantify the extraction behavior and demonstrate the effectiveness of reverse
      micelle enhanced extraction.

PMID- 15856091
TI  - Multi-walled carbon nanotubes for plasmid delivery into Escherichia coli cells.
AB  - Introduction of foreign genes into bacterial cells (transformation) is used for
      supplementing defective genes or providing additional biological functions.
      Transformation can be achieved using either chemical or physical methods, e.g.,
      electroporation. Bulk electroporation offers several advantages over chemical
      methods, including high transformation efficiency, but its application is limited
      due to the high numbers of cells and plasmids needed as a result of the high
      death rate of cells during this process, and the difficulty in electroporating
      single cells. Synthetic inorganic gene nanocarriers have received limited
      attention in the transformation of bacterial cells. Here we present a plasmid
      delivery system based on water dispersible multi-walled carbon nanotubes (CNTs)
      that can simultaneously target the bacterial surface and deliver the plasmids
      into the cells via temporary nanochannels across the cell envelope.
      Transformation experiments performed on E. coli provide evidence for the high
      potential of CNTs for nanoscale cell electroporation.

PMID- 15856092
TI  - Thermal optimisation of the Reimer-Tiemann reaction using thermochromic liquid
      crystals on a microfluidic reactor.
AB  - Microreactors incorporating thin film resistive heating elements for continuous
      flow organic synthesis are presented. Internal thermal conditions were monitored
      in real time using reflectance spectra of temperature sensitive thermochromic
      liquid crystals (TLC) in a collateral microfluidic network. To demonstrate the
      precise temperature control provided by this method, the thermal optimisation of
      the Reimer-Tiemann formylation of beta-naphthol was performed under hydrodynamic
      pumping regimes.

PMID- 15856093
TI  - Fabrication of SU-8 multilayer microstructures based on successive CMOS
      compatible adhesive bonding and releasing steps.
AB  - This paper describes a novel fabrication process based on successive wafer-level
      bonding and releasing steps for stacking several patterned layers of the negative
      photoresist EPON SU-8. This work uses a polyimide film to enhance previous low
      temperature bonding technology. The film acts as a temporary substrate where the
      SU-8 is photopatterned. The poor adhesion between the polyimide film and SU-8
      allows the film to be released after the bonding process, even though the film is
      still strong enough to carry out photolithography. Using this technique,
      successive adhesive bonding steps can be carried out to obtain complex 3-D
      multilayer structures. Interconnected channels with smooth vertical sidewalls and
      freestanding structures are fabricated. Unlike previous works, all the layers are
      photopatterned before the bonding process yielding sealed cavities and complex
      three-dimensional structures without using a sacrificial layer. Adding new SU-8
      layers reduces the bonding quality because each additional layer decreases the
      thickness uniformity and increases the polymer crosslinking level. The effect of
      these parameters is quantified in this paper. This process guarantees
      compatibility with CMOS electronics and MEMS. Furthermore, the releasing step
      leaves the input and the output of the microchannels in contact with the outside
      world, avoiding the usual slow drilling process of a cover. Hence, in addition to
      the straightforward integration of electrodes on a chip, this fabrication method
      facilitates the packaging of these microfluidic devices.

PMID- 15856094
TI  - Gentle cell trapping and release on a microfluidic chip by in situ alginate
      hydrogel formation.
AB  - Microfluidic devices are increasingly used to perform biological experiments on a
      single-cell basis. However, long-term stability of cell positions is still an
      issue. A novel biocompatible method for cell entrapment and release on a
      microchip is presented. It is based on the controlled formation of an alginate
      hydrogel by bringing two laminar flows of alginate and calcium ions in the range
      of 2 mM to 40 mM into contact. The resulting growth of a gel bar is used to
      enclose and immobilize yeast cells. Adding ethylenediaminetetraacetic acid (EDTA)
      to the alginate solution allows for control of the hydrogel growth, and by
      varying the ratio of Ca(2+) to EDTA concentrations gel growth or gel shrinkage
      can be induced at will. Trapped cells are released during shrinkage of the gel.
      The trapping efficiency for different cell speeds is investigated and the
      properties of gel growth are discussed using a diffusion model. Precise
      positioning of a single cell is demonstrated. The technique presented allows not
      only the reversible immobilization of cells under gentle conditions but also
      offers the potential of long-term cell cultures as shown by on-chip incubation of
      yeast cells. The procedure may provide a simple and fully biocompatible technique
      for a multitude of innovative experiments on cells in microsystems.

PMID- 15856095
TI  - Batch-mode mixing on centrifugal microfluidic platforms.
AB  - We present two novel fluidic concepts to drastically accelerate the process of
      mixing in batch-mode (stopped-flow) on centrifugal microfluidic platforms. The
      core of our simple and robust setup exhibits a microstructured disk with a round
      mixing chamber rotating on a macroscopic drive unit. In the first approach,
      magnetic beads which are prefilled into the mixing chamber are periodically
      deflected by a set of permanent magnets equidistantly aligned at spatially fixed
      positions in the lab-frame. Their radial positions alternatingly deviate by a
      slight positive and negative offset from the mean orbit of the chamber to
      periodically deflect the beads inbound and outbound during rotation. Advection is
      induced by the relative motion of the beads with respect to the liquid which
      results from the magnetic and centrifugal forces, as well as inertia. In a second
      approach--without magnetic beads--the disk is spun upon periodic changes in the
      sense of rotation. This way, inertia effects induce stirring of the liquids. As a
      result, both strategies accelerate mixing from about 7 minutes for mere diffusion
      to less than five seconds. Combining both effects, an ultimate mixing time of
      less than one second could be achieved.

PMID- 15856096
TI  - New carbon-rich materials for electronics, lithium battery, and hydrogen storage
      applications.
AB  - Methods for the preparation of novel carbon-rich materials for use in electronic
      devices, lithium batteries or possible hydrogen storage applications are
      presented.

PMID- 15856097
TI  - A unique site-selective reaction of ketones with new recyclable hypervalent
      iodine(III) reagents based on a tetraphenylmethane structure.
AB  - We have synthesized new recyclable reagents having a tetraphenylmethane backbone
      and used them in the site-selective alpha-tosyloxylation of ketones.

PMID- 15856098
TI  - Photochromism of a spirooxazine in the single crystalline phase.
AB  - The single crystals of a closed form spirooxazine spiro[azahomoadamantane
      isoquinolinoxazine] were found for the first time to undergo photocoloration
      processes consistent with photochromism in the single crystalline phase.

PMID- 15856099
TI  - A unique tetramer of 4:5 beta-cyclodextrin-ferrocene in the solid state.
AB  - A single crystal of a unique 4:5 inclusion complex between beta-cyclodextrin and
      ferrocene was prepared and the structure was determined by X-ray crystallographic
      analysis, showing that four of the five ferrocenes were included in the cavities
      of four beta-cyclodextrins along the axial orientation of the tetramer, while
      another was co-included between two beta-cyclodextrins from the equatorial
      orientation.

PMID- 15856100
TI  - Heteropolymetallic copper(II)-gold(III) dithiocarbamate [2]catenanes via magic
      ring synthesis.
AB  - A rare class of mixed-metal [2]catenane has been assembled via magic ring
      synthesis of dinuclear copper(II) and gold(III) dithiocarbamate macrocycles.

PMID- 15856101
TI  - Cellular internalization and targeting of semiconductor quantum dots.
AB  - Peptide-mediated internalization and organelle targeting of quantum dots.

PMID- 15856102
TI  - Conformational polymorphism of methacrylamide.
AB  - The industrially important compound methacrylamide crystallizes as concomitant
      conformational polymorphs; the monoclinic form contains only the s-cis conformer,
      while the orthorhombic form contains only the s-trans conformer.

PMID- 15856103
TI  - A supramolecular assembly of side-by-side polyimidazole tripod coils stabilized
      by pi-pi stacking and unique boric acid templated hydrogen bonding interactions.
AB  - The self assembly of (bis(1-methyl-imidazol-2-yl)methyl)(1-methyl-4-nitroimidazol
      2-yl)methyl)amine and boric acid results in a supramolecular structure containing
      bundled antiparallel imidazole-boric acid helices and boric acid filled one
      dimensional channels.

PMID- 15856104
TI  - Novel hybrid materials with high stability for electrically switched ion
      exchange: carbon nanotube-polyaniline-nickel hexacyanoferrate nanocomposites.
AB  - A novel and stable carbon nanotube-polyaniline-nickel hexacyanoferrate
      nanocomposite film has been synthesized by the electrodeposition method, and the
      feasibility for removing radioactive caesium through an electrically switched ion
      exchange process using the nanocomposite film has been evaluated in a mixture
      containing NaNO3 and CsNO3.

PMID- 15856105
TI  - Beta-sheet recognition in the non-interpenetrated and interpenetrated two
      dimensional coordination networks containing cavities.
AB  - Two types of secondary building units of CuI (Cu2I2 and Cu4I4) were shown to
      generate 2D-coordination networks of (4,4)-topology (non-interpenetrated and
      interpenetrated) with exo-bidentate ligands that contain diamide as spacer.

PMID- 15856106
TI  - Triple-stranded helices and zigzag chains of copper(I) 2-ethylimidazolate:
      solvent polarity-induced supramolecular isomerism.
AB  - The solvent effect of different polarities in hydro(solvo)thermal reaction of
      Cu(II) and 2-ethylimidazole leads to the generation of two supramolecular isomers
      of triple-stranded helical and zigzag chain-like structures of Cu(I) 2
      ethylimidazolate.

PMID- 15856107
TI  - Isolation and characterization of the first circular single-stranded polymetallic
      lanthanide-containing helicate.
AB  - A thorough examination of the disassembly of bimetallic triple-stranded
      lanthanide helicates [Ln2(Li)3]6+ (stoichiometry S = m/n = 2/3 = 0.67, global
      complexity GC = m + n = 2 + 3 = 5) in excess of metals shows the competitive
      formation of standard linear bimetallic complexes [Ln2(Li)2]6+ (S= 1.0, GC = 4),
      and circular trimetallic single-stranded helicates [Ln3(Li)3]9+ (S= 1.0, GC = 6).

PMID- 15856108
TI  - Low temperature catalytic conversion of methane to methanol by barium sulfate
      nanotubes supporting sulfates: Pt(SO4)2, HgSO4, Ce(SO4)2 and Pb(SO4)2.
AB  - Barium sulfate nanotubes perform excellently in supporting sulfates (Pt(SO4)2,
      HgSO4, Ce(SO4)2 and Pb(SO4)2) for low temperature catalytic conversion of methane
      to methanol under strongly acidic conditions in a conventional gas-phase reactor.

PMID- 15856109
TI  - Shape-controlled synthesis of Prussian blue analogue Co3[Co(CN)6]2 nanocrystals.
AB  - Prussian blue analogue Co3[Co(CN)6]2 nanostructures with morphologies of
      truncated nanocubes (polyhedra), cubes and rods, were synthesized in large
      quantities by a direct dissociation of the single-source precursor K3[Co(CN)6] in
      a microemulsion system; the molar ratio of H2O to surfactant and the
      concentration of K3[Co(CN)6] both played important roles in determining the shape
      of the product.

PMID- 15856110
TI  - Double discrimination by binding and reactivity in fluorescent metal ion
      detection.
AB  - Metal ion detection using a fluorescent dye containing reactive ester groups
      allows discrimination on the basis of the hydrolytic reactivities of metal ions,
      which display the same qualitative fluorescence response on binding only.

PMID- 15856111
TI  - Controlled release of plasmid DNA from gold nanorods induced by pulsed near
      infrared light.
AB  - Pulsed near-infrared laser irradiation induced release of plasmid DNA immobilized
      on gold nanorods without structural degradation, by selective excitation of
      longitudinal plasmon oscillation.

PMID- 15856112
TI  - Latent low-coordinate titanium imides supported by a sterically encumbering beta
      diketiminate ligand.
AB  - Addition of an equal molar quantity of R- (R = Me, SiMe3) to complex
      (Nacnac)Ti=NAr(OTf) (Nacnac- =[ArNC(tBu)]2CH, Ar = 2,6-iPr2C6H3) forms the imido
      alkyl (Nacnac)Ti=NAr(R), which can be readily protonated to afford
      [(Nacnac)Ti=NAr(L)]+ (L = THF, Et2O, eta1-C6H5NMe2), or treated with B(C6F5)3 to
      afford the zwitterion (Nacnac)Ti=NAr(micro-CH3)B(C6F5)3.

PMID- 15856113
TI  - Tandem oxidation processes: a combined phosphorus- and sulfur-ylide approach to
      polysubstituted cyclopropanes.
AB  - A new manganese dioxide-mediated tandem oxidation process (TOP) has been
      developed which, by suitable combination of stabilised phosphorus- and sulfur
      ylides, allows the direct conversion of allylic alcohols or alpha-hydroxyketones
      into polysubstituted cyclopropanes.

PMID- 15856114
TI  - Corona-induced photoxidation of alcohols and hydrocarbons over TiO2 in the
      absence of a UV light source - a novel and environmentally friendly method for
      oxidation.
AB  - Corona-induced photooxidation is a novel oxidation methodology for the efficient
      oxidation of alcohols and hydrocarbons utilizing the advantage of both the high
      oxidizing power of ozone formed in the reactor as well as the photooxidation
      capability of the UV light generated during the corona discharge.

PMID- 15856115
TI  - Volatile solvent-free solid-state polymer-sensitized TiO2 solar cells with
      poly(3,4-ethylenedioxythiophene) as a hole-transporting medium.
AB  - Novel, volatile solvent free, solid-state solar cells were fabricated with
      mesoporous TiO2 electrodes sensitized using thiophene derivatives containing
      carboxyl groups and in situ electropolymerized poly(3,4-ethylenedioxythiophene)
      as a hole-transporting material together with the ionic liquid 1-ethyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)amide and lithium
      bis(trifluoromethanesulfone)imide as additives for charge transport promotion.

PMID- 15856116
TI  - A robust three-dimensional mesoporous Ag/TiO2 nanohybrid film.
AB  - A Ag/TiO2 nanocomposite, in which silver nanoparticles are highly dispersed in
      the uniformly sized pores of a cubic mesoporous TiO2 molecular-sieve film, has
      been fabricated.

PMID- 15856117
TI  - Total synthesis of viridiofungin A.
AB  - Viridiofungin A, a member of amino alkyl citrate antibiotics from Trichoderma
      viride, was enantioselectively synthesized in naturally occurring form for the
      first time, employing regio- and stereoselective opening of the chiral glycidate
      with vinylmagnesium bromide and alkene cross metathesis of the citric acid core
      and hexadec-15-en-8-one as key steps.

PMID- 15856118
TI  - Double stimuli-responsive behavior of aliphatic poly(urethane-amine)s derived
      from supercritical carbon dioxide.
AB  - Copolymeric products from 2-methylaziridine and carbon dioxide showed sharp and
      rapid phase transitions in response to both temperature and pH; the responsive
      property can be controlled by varying the reaction conditions whilst maintaining
      the supercritical state.

PMID- 15856119
TI  - Synthesis and structures of a 3-sila-beta-diketiminatomagnesium bromide,
      ketenimide and triflate.
AB  - The crystalline compounds [Mg(Br)(L)(thf)].0.5Et2O [L = {N(R)C(C6H3Me2-2,6)}2SiR,
      R = SiMe3] (1), [Mg(L){N=C=C(C(Me)=CH)2CH2}(D)2] [D = NCC6H3Me2-2,6 (2), thf (3)]
      and [{Mg(L)}2{mu-OSO(CF3)O-[mu}2] (4) were prepared from (a) Si(Br)(R){C(C6H3Me2
      2,6)=NR}2 and Mg for (1), (b) [Mg(SiR3)2(thf)2] and 2,6-Me2C6H3CN (5 mol for (2),
      3 mol for (3)), and (c) (2) + Me3SiOS(O)2CF3 for (4); a coproduct from (c) is
      believed to have been the trimethylsilyl ketenimide Me3SiN=C=C{C(Me)=CH}2CH2 (5).

PMID- 15856120
TI  - Silicon-based nanowires from silicon wafers catalyzed by cobalt nanoparticles in
      a hydrogen environment.
AB  - We present here the synthesis of silicon-based nanowires directly from silicon
      wafers at high temperatures and in the presence of cobalt nanoparticles and
      hydrogen gas. All three ingredients were critical to the growth of Si-based
      nanowires, which were between 5-60 nm in diameter and microm-mm long. Both
      heavily coiled and straight Si-based nanowires were made. Experimental evidence
      suggested that the sources of silicon for the nanowires growth were in the gas
      phase.

PMID- 15856121
TI  - Ionic liquid high temperature gas sensors.
AB  - An ionic liquid piezoelectric gas sensor was demonstrated for detection of polar
      and nonpolar organic vapors at high temperature with fast linear and reversible
      response.

PMID- 15856122
TI  - Total syntheses of fully lipidated glycosylphosphatidylinositol anchors of
      Toxoplasma gondii.
AB  - Modular syntheses of the glycosylphosphatidylinositol anchors of Toxoplasma
      gondii using a highly convergent strategy are reported.

PMID- 15856123
TI  - Synthesis of linear aldehydes from internal olefins in water.
AB  - We show here, for the first time, that the carbonylation of internal olefins in a
      biphasic water system is possible. It is shown that control of the pH and CO
      partial pressure are important factors for successful reactions. Interestingly,
      the water-soluble catalyst leads to significantly higher regioselectivity
      compared to similar catalysts soluble in organic solvents. The obtained n/i
      selectivities exceed all known literature data and the catalyst can be easily
      reused several times.

PMID- 15856124
TI  - Catalytic formation of C-O bonds by alkene activation: Lewis acid
      cycloisomerisation of olefinic alcohols.
AB  - Tin(IV) trifluoromethanesulfonate has been found to be an excellent catalyst for
      the cycloisomerisation of non-activated and differently substituted olefinic
      alcohols to cyclic ethers.

PMID- 15856125
TI  - [What is the influence of the approach to intraoperative measurement of the knee
      joint on total knee arthroplasty? A navigation-controlled study on a cadaver
      knee].
AB  - Correct postoperative leg alignment and stability of the total knee prosthesis
      over the full range of movement is one critical factor for successful TKA. The
      anatomic approach is still the subject of controversy. The aim of our study was
      to elucidate the influence of the surgical approach on the ligament balancing and
      the anterioposterior limb axis.On five cadaver knees we studied the influence of
      the subvastus, midvastus, medial parapatellar, rectus snip, and tuberosity
      osteotomy approaches on the anterioposterior leg axis in extension and the
      rotation of the femoral component in flexion. Measurements were performed and
      documented by CT-free Ci-Navigation-System. Ligament tension was measured with a
      tensor device. We found that the subvastus approach leads to less widening of the
      medial compartment than all other approaches in extension. In 90 degrees flexion
      we found a similar influence. The consecutive release from subvastus to midvastus
      to medial parapatellar approach leads to a further opening of 0.5-1 degrees
      valgus in extension as well as in flexion. An everted patella amplifies this
      influence. The surgeon has to be aware of the impact on the ligament situation in
      regard to the anatomic approach when ligament balancing and soft tissue releases
      are carried out. Patella eversion should be avoided when managing soft tissues.

PMID- 15856127
TI  - [Paraparesis following stable L4 burst fracture Possible correlation with
      preexisting degenerative stenosis of the spinal canal].
AB  - A patient with degenerative stenosis of the lumbar spinal canal developed
      paraparesis of both legs following a stable L4 burst fracture. However, neither
      the stenosis nor the fracture have caused a significant narrowing of the spinal
      canal. Surgical decompression and dorsal stabilization has led to relief of the
      neurological deficit. This case demonstrates that even a stable burst fracture
      may cause paraparesis and that a degenerative spinal canal stenosis is a
      predisposing factor.

PMID- 15856126
TI  - [Traumatic aortic injuries in severely injured patients].
AB  - Herein we report our results of treatment of traumatic aortic ruptures in
      severely injured patients with either open surgery or endovascular stent graft
      repair. Data were analyzed retrospectively from the trauma registry of the DGU
      (Deutsche Gesellschaft fur Unfallchirurgie) over a time period from 1993 through
      2002. All patients with traumatic rupture of the aorta were included and analyzed
      for injury severity (ISS), blood pressure (mmHg), hemoglobin (mg/%), and AIS
      (Abbreviated Injury Score) of the thoracic, abdominal, and upper extremity
      regions. Patients treated between 1998 and 2002 were further examined (operation
      within 24 h, duration of intervention, blood transfusion, and lethality with
      regard to either open surgical or endoluminal stent graft repair). Of 14,110
      patients, 100 (0.7%) suffered from acute aortic rupture. Mean age was 38 years
      (+/-19) with an inhospital lethality of 39% (n=39). Mean ISS was 41 (+/-14); 36
      patients were treated by open surgery and 5 patients by a stent-assisted
      endoluminal procedure. Lethality was 17% for open surgery and 0% for stent graft
      repair. Endovascular approach to traumatic rupture of the aorta is feasible and
      safe. It has been shown to reduce inhospital lethality and may offer an
      alternative to open surgery for severely injured patients.

PMID- 15856128
TI  - [Avulsion fracture of the calcaneal tuberosity in athletes].
AB  - Avulsion fractures of the calcaneal tuberosity are rare injuries. Several
      surgical treatment options have been described. The size of the calcaneal
      fragment is the limiting factor in choosing the method for restoration. Finding
      the right type of fixation modality remains challenging in this rare kind of
      injury. In the case presented one Mitek Super Anchor was used to reattach the
      small fragment of the tuberosity to the calcaneus. Stable fixation with bony
      reunion and excellent functional outcome were achieved by this technique within
      10 weeks. Therefore, we recommend the use of an anchor system for the treatment
      of small fragment calcaneal avulsion fractures.

PMID- 15856129
TI  - [Simultaneous bilateral ventral and dorsal shoulder dislocation following an
      epileptic convulsion--a rare combination of injuries].
AB  - We report about a 29 year old male patient who had a simultaneous bilateral
      ventral and dorsal shoulder dislocation. The dislocation happened during a first
      incident of an epileptic convulsion, previously not diagnosed. On the right
      shoulder following a closed reduction manoeuvre a dislocation fracture was seen.
      It needed operative open reduction and fixation with angular stable plate
      osteosynthesis. The locked dorsal shoulder dislocation on the left was operated
      dorsally secondary via a dorsal approach. In a first step the reduction was
      carried out and in the same intervention the humeral head defect was lifted and
      supported in a closed technique under radiographic control.6 months
      postoperatively the patient was free of pain in both shoulder joints. The range
      of motion was unimpeded on the left and only with slight deficits in abduction
      and anteversion on the right. The diagnostics and the treatment strategy for this
      rare injury combination are described critically in this paper.

PMID- 15856130
TI  - [ARDS after unreamed femoral nailing].
AB  - An 18-year-old male patient sustained right-sided femoral and 2nd degree open
      tibial shaft fractures following a motorcycle accident. Further injuries, and
      thoracic injury in particular, were excluded clinically and radiologically. Early
      stabilization of the fractures was achieved by external fixation of the tibia
      followed by unreamed femoral nailing.Postoperatively, severe deterioration of
      pulmonary function led to the progressive development of an adult respiratory
      distress syndrome (ARDS) and necessitated extracorporal membrane oxygenation
      (ECMO) of the ventilated patient for 89 h. Subsequently, the patient's gas
      exchange parameters improved allowing extubation 1 week after the accident.
      Secondary tibia nailing and further recovery of the patient were uneventful.

PMID- 15856131
TI  - Does pelvic organ prolapse quantification exam predict urethral mobility in
      stages 0 and I prolapse?
AB  - OBJECTIVE: To determine if women with anterior support stages 0 or I by pelvic
      organ prolapse quantification (POP-Q) system require Q-tip testing to assess
      urethral mobility. METHODS: A prospective study of 134 women presenting for
      urogynecologic evaluation were examined and assigned stages of anterior wall
      support according to the POP-Q system. A Q-tip test was performed and urethral
      hypermobility was defined as a straining angle > or =30 degrees. The Spearman
      correlation coefficient was used to assess degree of correlation between POP-Q
      point Aa position and Q-tip values. RESULTS: The correlation coefficient between
      point Aa position and Q-tip angle was r = 0.787 (P < 0.001). Urethral
      hypermobility was noted in 91% of stage I and 100% of stage II-IV patients. The
      positive predictive value of Q-tip angle > or =30 degrees in stage I-IV prolapse
      was 99%. CONCLUSION: The POP-Q system is highly predictive of straining urethral
      angle in all stages of prolapse.

PMID- 15856132
TI  - Epidemiology of prolapse and incontinence questionnaire: validation of a new
      epidemiologic survey.
AB  - The epidemiology of prolapse and incontinence questionnaire (EPIQ) was developed
      to screen for female pelvic floor disorders (PFD). Content and face validity,
      reliability, internal consistency and criterion validity of the EPIQ to detect
      the presence of pelvic organ prolapse (POP), stress urinary incontinence (SUI),
      overactive bladder (OAB) and anal incontinence (AI) is presented. Cronbach's
      alpha; Spearman's, kappa, intraclass correlations, factor analysis and Chi
      Squared tests were used for analysis. Questions related to PFD proved internally
      consistent (alpha = 0.91) and reproducible (correlations >0.70) for all but three
      items on the EPIQ. Positive and negative predictive values of the EPIQ to detect
      PFD were: POP = 76% and 97%, SUI = 88% and 87%, OAB = 77% and 90% and AI = 61%
      and 91% respectively. EPIQ is a psychometrically validated screening instrument
      that may identify women at high risk of having pelvic floor disorders in large
      undiagnosed populations.

PMID- 15856133
TI  - Desulfovibrio brasiliensis sp. nov., a moderate halophilic sulfate-reducing
      bacterium from Lagoa Vermelha (Brazil) mediating dolomite formation.
AB  - A novel halotolerant sulfate-reducing bacterium, Desulfovibrio brasiliensis
      strain LVform1, was isolated from sediments of a dolomite-forming hypersaline
      coastal lagoon, Lagoa Vermelha, in the state of Rio de Janeiro, Brazil. The cells
      are vibrio-shaped and 0.30 to 0.45 microm by 1.0 to 3.5 microm in size. These
      bacteria mediate the precipitation of dolomite [CaMg(CO3)2] in culture
      experiments. The strain was identified as a member of the genus Desulfovibrio in
      the delta-subclass of the Proteobacteria on the basis of its 16S rRNA gene
      sequence, its physiological and morphological properties. Strain LVform1 is
      obligate sodium-dependent and grows at NaCl concentrations of up to 15%. The 16S
      rRNA sequence revealed that this strain is closely related to Desulfovibrio
      halophilus (96.2% similarity) and to Desulfovibrio oxyclinae (96.8% similarity),
      which were both isolated from Solar Lake, a hypersaline coastal lake in the
      Sinai, Egypt. Strain LVform1 is barotolerant, growing under pressures of up to
      370 bar (37 MPa). We propose strain LVform1 to be the type strain of a novel
      species of the genus Desulfovibrio, Desulfovibrio brasiliensis (type strain
      LVform1 = DSMZ No. 15816 and JCM No. 12178). The GenBank/EMBL accession number
      for the 16S rDNA sequence of strain LVform1 is AJ544687.

PMID- 15856134
TI  - Comparison of bacterial communities in the alkaline gut segment among various
      species of higher termites.
AB  - The first proctodeal (P1) segment in the hindgut of certain higher termites shows
      high alkalinity. We examined the bacterial diversity of the alkaline P1 gut
      segments of four species of higher termites by T-RFLP and phylogenetic analyses
      based on PCR-amplified 16S rRNA genes. The bacterial community of the P1 segment
      was apparently different from that of the whole gut in each termite. Sequence
      analysis revealed that Firmicutes (Clostridia and Bacilli) were dominant in the
      P1 segments of all four termites; however, the phylogenetic compositions varied
      among the termites. Although some of the P1 segment-derived sequences were
      related to the sequences previously reported from the alkaline digestive tracts
      of other insects, most of them formed phylogenetic clusters unique to termites.
      Such "termite P1 clusters" were distantly related to known bacterial species as
      well as to sequences reported from alkaline environments in nature. We
      successfully obtained enrichment cultures of Clostridia- and Bacilli-related
      bacteria, including putative novel species under anaerobic alkaline conditions
      from the termite guts. Our results suggest that the alkaline gut region of
      termites harbors unique bacterial lineages and are expected to be a rich
      reservoir of novel alkaliphiles yet to be cultivated.

PMID- 15856135
TI  - Genetic analysis and conservation of the endangered Canary Island woody sow
      thistle, Sonchus gandogeri (Asteraceae).
AB  - Sonchus gandogeri, a woody sow-thistle, is an endangered Canary Island endemic
      with only two known populations, one in the El Golfo and another in the Las
      Esperillas of El Hierro. Amplified fragment length polymorphism (AFLP) markers
      were used to assess the genetic variation within and among populations. The mean
      genetic diversity of two populations was estimated to be 0.380, and the El Golfo
      population (0.380) had higher genetic diversity than the southeastern one
      (0.268). The unbiased Nei's genetic identity between the two populations was
      0.846. The mean genetic diversity of S. gandogeri was much higher than that of
      the other endangered plant species. This is perhaps due to breeding system, life
      form, extinction, and/or introgressive hybridization and hybrid origin of the
      taxon. This study also indicates that the two populations are not strongly
      differentiated (G(ST)=0.149). This study suggests that S. gandogeri is more
      likely to become extinct due to environmental or demographic forces than genetic
      factors, such as inbreeding depression. More strict control of introduced
      herbivores is necessary to protect these populations, and germplasm collection
      for ex situ conservation is needed.

PMID- 15856137
TI  - Tularemia after a dormouse bite in Switzerland.

PMID- 15856138
TI  - Candida species distribution in bloodstream cultures in Lyon, France, 1998-2001.
AB  - In order to determine the types of Candida spp. isolated from bloodstream
      cultures in Lyon, France, a retrospective study of isolates collected at five
      different bacteriology laboratories from 1998 to 2001 was conducted. During this
      period Candida spp. were isolated from 190 patients hospitalized in the internal
      medicine (32%), hematology (23%) and surgery (23%) wards, and in intensive care
      units (22%). C. albicans was the leading cause of Candida infection (49.5%),
      followed by C. glabrata (12.6%) and C. parapsilosis (12.1%). Among the onco
      hematology patients, the major cause of candidemia was C. krusei (34%), followed
      by C. albicans (19%), while these two species were identified in 4% and 59% of
      patients in the other wards, respectively. In the single onco-hematology ward
      that was specialized in treating acute myeloid leukemia, 14 C. krusei isolates
      were identified in this study, which contrasts with the single C. krusei isolate
      recorded between 1992 and 1996. Since C. krusei has inherent resistance to the
      antifungal agent fluconazole, prophylactic use of fluconazole in these patients
      was investigated, but no relationship between these two parameters was found.

PMID- 15856142
TI  - [Techniques for functional tissue and organ replacement using postnatal stem
      cells].
AB  - Postnatal stem cells play a decisive role in cell-based therapies due to their
      high proliferation activity and functional plasticity. On the one hand, basic
      research in cell biological processes of adult stem cells is crucial in order to
      establish them as therapeutic tools. On the other hand, development and
      enhancements of appropriate techniques are required: we need to establish defined
      technologies for extraction and differentiation of stem cells and to develop
      adequate cell carrier devices, scaffolds, and bioreactors for in vitro purposes.
      Furthermore, it is an interdisciplinary challenge to consider logistical aspects
      concerning isolation, transport, and storage of stem cells in order to use them
      in a wide range of activities in regenerative medicine. In this review we present
      the current methods of work and research on adult stem cells. We explain their
      therapeutic use and define requirements for future technological developments for
      work with postnatal stem cells.

PMID- 15856143
TI  - [Guidelines for rehabilitation of dermatological diseases].
AB  - Guidelines for dermatological rehabilitation are based on the International
      Classification of Functioning, Disabilities and Health (ICF), which includes
      context factors such as physical environment, socioeconomic conditions, and the
      personal situation of the patient. Guidelines give specific recommendations for
      personal conditions of rehabilitation, staff, equipment, process of treatment,
      and evaluation. They assist doctors, patients, and public institutions in
      orientation and decision making. The latest publications are a joint summary
      obtained from experts, with substantial participation of the social insurance
      agencies, and demonstrate the growing importance of guidelines which are the
      result of a compromise between the conflicting interests of medical progress on
      the one hand and economic restrictions on the other. Consequences for allocation
      of financial resources in the health system are discussed.

PMID- 15856144
TI  - [Varying characteristics of subcutaneous and dermal leiomyosarcomas. Two case
      reports and literature review].
AB  - Cutaneous leiomyosarcomas (LMS) originating from smooth muscle of the skin are
      rare malignant neoplasms. Preferential sites are hair-bearing areas, especially
      the legs. We report two patients in their 5th and 7th decade, in whom
      leiomyosarcomas were encountered in the lower leg and the capillitium,
      respectively. Histologically, the former was found to be a dermal leiomyosarcoma
      with subcutaneous infiltration, the latter an exclusively dermal tumor. The LMS
      of the lower leg had been excised three years previously in a different
      institution and had been diagnosed as a leiomyoma. Both lesions were excised with
      adequate safety margins in our institution and within a two-year postoperative
      observation period no recurrences were encountered. Dermal leiomyosarcomas have a
      33% recurrence rate while that of subcutaneous leiomyosarcomas show is 50%. In
      contrast to exclusively dermal tumors, subcutaneous LMS show a tendency for
      hematogenic and lymphogenic metastases. Therapy of choice is excision with wide
      safety margins.

PMID- 15856145
TI  - [Interdisciplinary management of severe midfacial trauma].
AB  - The anatomy of the craniofacial skeleton is complex, the bones being closely
      associated with important neurological structures and sensory organs. The face
      itself is intimately associated with hereditary features and emotional feelings,
      and, as a consequence, midfacial trauma may lead to important aesthetic,
      functional and personal problems. Patients suffering from severe midfacial
      injuries reveal significant concomitant lesions of other body regions in a high
      percentage of cases. Thus, midfacial trauma patients require an elaborate
      interdisciplinary regimen of diagnostics and therapy. This paper provides on
      overview of the interdisciplinary management of midfacial trauma patients. The
      overlapping multispecialty fields are analyzed with emphasis on the viewpoint of
      the practicing ENT-surgeon. Assuming that basic principles of trauma care are
      known, interdisciplinary strategies and specific responsibilities for problem
      solving are provided. The ENT-surgeon is guided and called upon to play an active
      and cooperative part in the midfacial traumatology team.

PMID- 15856146
TI  - Prevalence of cardiac beta-myosin heavy chain gene mutations in patients with
      hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is a frequent, autosomal-dominant cardiac
      disease and manifests predominantly as left ventricular hypertrophy. Mutations in
      the cardiac beta-myosin heavy chain gene (MYH7) are responsible for the disease
      in about 30% of cases where mutations were identified. We clinically evaluated a
      large group of 147 consecutive HCM patients from three cardiology centers in
      Germany, Poland, and Kyrgyzstan according to the same protocol. The DNA of the
      patients was systematically analyzed in the whole coding region of the MYH7 gene
      using PCR, single-strand conformation polymorphism analysis, and automated
      sequencing. Eleven different missense mutations (including seven novel ones) in
      11 unrelated patients were identified, showing a mutation frequency of 7.5% in
      the study population. We further examined the families of five patients (three of
      German, one of Polish, and one of Kyrgyz origin) with 32 individuals in total. We
      observed a clear, age-dependent penetrance with onset of disease symptoms in the
      fourth decade of life. Genotype-phenotype correlations were different for each
      mutation, whereas the majority was associated with an intermediate/malign
      phenotype. In conclusion, we report a systematic molecular screening of the
      complete MYH7 gene in a large group of consecutive HCM patients, leading to a
      genetic diagnosis in 38 individuals. Information about the genotype in an
      individual from one family could be very useful for the clinician, especially
      when dealing with healthy relatives in doubt of their risk about developing HCM.
      The increasing application of genetic screening and the increasing knowledge
      about genotype-phenotype correlations will hopefully lead to an improved clinical
      management of HCM patients.

PMID- 15856147
TI  - [Evaluation of image quality of the Iso C3D image processor in comparison to
      computer tomography. Use in the pelvic area].
AB  - Intraoperative 3-D visualization using the Siremobil Iso C(3D) (Siemens,
      Erlangen, Germany) has been approved for use in spine and long bone surgery since
      its recent clinical launch. In preparation for the clinical use of the Siremobil
      Iso C(3D) in pelvic surgery, the aim of this study was to grade the quality of
      visualization in comparison with the gold standard of computer tomography in four
      therapy relevant pelvic regions in eight human cadavers, including SI screws to
      exemplify implants in the dorsal pelvic ring. Besides the influence of the body
      mass index and the interference of metal artefacts, visualization quality was
      evaluated in different pelvic regions (sacroiliac joint, acetabulum, femoral neck
      and anterior pelvic ring) using a score with five subgroups, rating the
      applicability of Siremobil Iso C(3D) in pelvic surgery. The grading of image
      quality in comparable standard projections was performed independently by three
      surgeons and three radiologists.Visualization quality appeared sufficient for
      both intraoperative and postoperative control in cases with a known preoperative
      diagnosis. There was no influence of body mass index found in any of the eight
      cadavers. Implants positioned in the dorsal pelvic ring reduced visualization
      quality, but sufficient estimation of bony structures was still possible. For
      primary diagnostics, computer tomography remains a clearly superior option due to
      better image quality. For intraoperative control of the reduction and positioning
      of implants in pelvic surgery, however, the additional intraoperative use of
      Siremobil Iso C(3D) is considered to offer clear advantages over current 2-D C
      arm visualization tools.

PMID- 15856148
TI  - [Rhabdomyolysis after administration of diclofenac].
AB  - Rhabdomyolysis may develop after various traumatic and nontraumatic
      circumstances. The use of lipid-lowering statins as well as the abuse of
      stimulants such as methylendioxymethamphetamine (ecstasy) can lead to fatal
      rhabdomyolysis with acute renal failure. We describe a case of diclofenac-induced
      rhabdomyolysis after a cumulative dose of 200 mg per os with consecutive critical
      increase of the creatine kinase and myoglobin. Prescription of diclofenac should
      therefore be done with caution. In cases of emergent myalgias, immediate testing
      of creatine kinase and myoglobin is mandatory to exclude fatal rhabdomyolysis
      with acute renal failure.

PMID- 15856149
TI  - Depression of brain dopamine and its metabolite after mating in European honeybee
      (Apis mellifera) queens.
AB  - To explore neuro-endocrinal changes in the brain of European honeybee (Apis
      mellifera) queens before and after mating, we measured the amount of several
      biogenic amines, including dopamine and its metabolite in the brain of 6- and 12
      day-old virgins and 12-day-old mated queens. Twelve-day-old mated queens showed
      significantly lower amounts of dopamine and its metabolite (N-acetyldopamine)
      than both 6- and 12-day-old virgin queens, whereas significant differences in the
      amounts of these amines were not detected between 6- and 12-day-old virgin
      queens. These results are explained by down-regulation of both synthesis and
      secretion of brain dopamine after mating. It is speculated that higher amounts of
      brain dopamine in virgin queens might be involved in activation of ovarian
      follicles arrested in previtellogenic stages, as well as regulation of their
      characteristic behaviors.

PMID- 15856150
TI  - Highly controlled nest homeostasis of honey bees helps deactivate phenolics in
      nectar.
AB  - Honey bees have a highly developed nest homeostasis, for example, maintaining low
      CO2 levels and stable nest temperatures at 35 degrees C.We investigate the role
      of nest homeostasis in deactivating phenolic compounds present in the nectar of
      Aloe littoralis. We show that the phenolic content in nectar was reduced (from
      0.65% to 0.49%) after nectar was incubated in a nest of Apis cerana, and that it
      was reduced still more (from 0.65% to 0.37%) if nectar was mixed with
      hypopharyngeal gland proteins (HGP) of worker bees before being placed inside a
      nest. HGP had little effect on samples outside a nest, indicating that nest
      conditions are necessary for HGP to deactivate phenolics in nectar. Consequently,
      the highly controlled nest homeostasis of honey bees facilitates direct
      deactivation of phenolics in nectar, and plays a role in the action of HGP as
      well.

PMID- 15856151
TI  - [Exophiala species--a rare cause of endocarditis with cerebral abscess
      formation].
AB  - Exophiala species belong to the dematiaceous fungi. Occurring worldwide, they are
      a rare cause of human infection. We present the case of a 75-year-old
      immunocompetent patient with a cardiogenic embolic anterior cerebral artery
      infarction. Echocardiography revealed endocarditis of the aortic valve.
      Antibiotic therapy was initiated after susceptibility testing (blood cultures
      were positive for Staphylococcus aureus, and liquor was normal), with a
      subsequent fall in serologic markers of infection and resolution of the signs of
      endocarditis on echocardiography. However, 6 weeks after initiation of antibiotic
      therapy, abscesses were seen in the infarct region on CT scan, although
      antimicrobial treatment was still continued. At this stage, the CSF showed an
      inflammatory process, and Exophiala species, susceptible to voriconazol, could be
      detected in liquor cultures. However, antifungal therapy with voriconazol could
      not prevent severe sepsis and death from multiorgan failure. Autopsy revealed the
      clinically supposed Exophiala endocarditis with metastatic cerebral abscesses. In
      accordance with other published case reports, a fatal outcome in disseminated
      Exophiala infection might only be prevented by aggressive therapy consisting of
      early surgical removal of the foci and combined antifungal agents.

PMID- 15856152
TI  - [Psychiatric aspects of plant poisonings].
AB  - Plant poisonings have been reported since ancient times. Despite this, little
      attention is paid to intoxications with herbal poisons by psychiatric literature
      and the danger from poisonous plants is commonly underestimated. This problem is
      discussed here, and advice for the prevention of plant poisonings and generally
      dealing with patients intoxicated by herbal poisons is given.

PMID- 15856153
TI  - [HERNS. A rare, hereditary, multisystemic disease with cerebral microangiopathy].
AB  - Hereditary endotheliopathy with retinopathy, nephropathy, and stroke (HERNS) is
      an autosomally dominant inherited, multisystemic disease presenting with
      leukoencephalopathy, progressive visual loss, and nephropathy. Furthermore,
      psychiatric symptoms and migraine may occur. Magnetic resonance imaging has
      identified contrast-enhancing cerebral lesions with surrounding vasogenic edema.
      Electron microscopy has shown alterations in the arterioles and capillaries
      consisting of multilayered basement membranes in brain, kidney, and skin
      biopsies. Linkage analysis has mapped the disease locus to chromosome 3p21. At
      the present time, no effective treatment is known. This article gives a summary
      of the clinical, morphological, genetical, and pathological characteristics of
      HERNS.

PMID- 15856154
TI  - [Quality control in imaging standards for stroke diagnosis].
AB  - Hospitals in "Rhineland-Palatinate" and "Saarland" as well as in other German
      states are using benchmarking in quality control and to improve diagnostic
      procedures and treatment in stroke. The goal is a continuous learning process in
      which participants improve their performance by comparing themselves to the
      highest quality care. CCT/MRI procedures are an important tool in stroke therapy
      and prophylaxis. Structural quality was good in all 39 participating hospitals.
      The best evidence-based indicator in quality control of CCT/MRI procedures is the
      process quality in performing these procedures within 3 h after stroke onset.
      Process quality was better in hospitals that cared for many stroke patients than
      in those with fewer cases. The latter hospitals also had less clinical and
      diagnostic competence. Benchmarking in quality control was successful because
      over the years improvement in stroke management was obvious in the participating
      hospitals.

PMID- 15856155
TI  - [Intra-arterial thrombolysis of the middle cerebral artery: an overview].
AB  - Until 1996, treatment of strokes consisted exclusively of efforts to prevent
      recurrence. The development of intravenous and intra-arterial thrombolysis
      changed the approach to a causal therapy. This article provides an overview of
      state-of-the-art intravenous and intra-arterial therapeutic concepts and attempts
      to define the position of the local intra-arterial fibrinolysis approach.

PMID- 15856156
TI  - [Neuroblastoma].
AB  - Neuroblastoma is an embryonal tumour of childhood. Primary tumours are localized
      retroperitoneally or abdominally. Neuroblastoma produce catecholamine metabolites
      which are used as tumour markers. MIBG scintigraphy in addition to ultrasound and
      nuclear magnetic resonance tomography allow specific imaging of the tumour
      tissue. In young patients, spontaneous remissions are not uncommon, whereas the
      outcome in older children is poor despite intensive treatment. Therefore, the
      treatment of neuroblastoma must be risk adapted. The 5 year overall survival
      rates in the German NB97 trial were 96+/-1% in the observation group, 89+/-3% in
      the median risk group, and 50+/-3% in the high risk group.

PMID- 15856157
TI  - [Transurethral resection for benign prostatic hyperplasia. current developments].
AB  - Transurethral resection of the prostate still represents the "gold standard" in
      surgical treatment of symptomatic benign prostatic enlargement (BPE). New demands
      were made on transurethral electrosurgery with the appearance of alternative,
      minimal invasive procedures. Bleeding complications had to be reduced. Different
      attempts were made to improve the conventional TURP. Band loops and roller bars
      were developed in order to gain a more effective coagulation during the cutting
      process by a larger tissue contact. Major advances could be achieved by
      modifications of the high-frequency generator. Improved procedures like the
      "Coagulating-Intermittent-Cutting" (CIC), the "Instant-Response-", as well as the
      "Dry-Cut-Technology" combine cutting and coagulating effects to realize lowered
      bleeding and an efficient resection process. The introduction of bipolar currency
      flow opens the possibility of conventional TUR-P with saline solutions and thus
      to the theoretical avoidance of the TUR-syndrome. By the neoadjuvant use of
      5alpha-reductase-inhibitors before planned TUR-P, bleeding- and irrigation fluid
      absorption should be reduced by lowering perfusion and the size of the prostate.
      Regarding these innovative approaches which improve the surgical standard and
      minimize the risk of perioperative complications, transurethral electrosurgery
      remains the method of choice in instrumental therapy of symptomatic BPE. In the
      future efficacy and costs will be comparable to those of the transurethral laser
      resection or laser-vaporisation.

PMID- 15856158
TI  - Identification of a major QTL together with several minor additive or epistatic
      QTLs for resistance to fire blight in apple in two related progenies.
AB  - Although fire blight, caused by the bacterium Erwinia amylovora, is one of the
      most destructive diseases of apple (Malus x domestica) worldwide, no major,
      qualitative gene for resistance to this disease has been identified to date in
      apple. We conducted a quantitative trait locus (QTL) analysis in two F(1)
      progenies derived from crosses between the cultivars Fiesta and either Discovery
      or Prima. Both progenies were inoculated in the greenhouse with the same strain
      of E. amylovora, and the length of necrosis was scored 7 days and 14 days after
      inoculation. Additive QTLs were identified using the MAPQTL: software, and
      digenic epistatic interactions, which are an indication of putative epistatic
      QTLs, were detected by two-way analyses of variance. A major QTL explaining 34.3-
      46.6% of the phenotypic variation was identified on linkage group (LG) 7 of
      Fiesta in both progenies at the same genetic position. Four minor QTLs were also
      identified on LGs 3, 12 and 13. In addition, several significant digenic
      interactions were identified in both progenies. These results confirm the complex
      polygenic nature of resistance to fire blight in the progenies studied and also
      reveal the existence of a major QTL on LG7 that is stable in two distinct genetic
      backgrounds. This QTL could be a valuable target in marker-assisted selection to
      obtain new, fire blight-resistant apple cultivars and forms a starting point for
      discovering the function of the genes underlying such QTLs involved in fire
      blight control.

PMID- 15856159
TI  - The L locus, one of complementary genes required for anthocyanin production in
      onions (Allium cepa), encodes anthocyanidin synthase.
AB  - Bulb color in onions (Allium cepa) is an important trait, but its complex,
      unclear mechanism of inheritance has been a limiting factor in onion cultivar
      improvement. The identity of the L locus, which is involved in the color
      difference between Brazilian yellow and red onions, is revealed in this study. A
      cross was made between a US-type yellow breeding line and a Brazilian yellow
      cultivar. The segregation ratio of nine red to seven yellow onions in the F(2)
      population supports the involvement of two complementary genes in anthocyanin
      production in the F(1) hybrids. The high-performance liquid chromatography (HPLC)
      and reverse-transcriptase (RT)-PCR analysis of the Brazilian yellow onions
      indicated that the genes are involved late in the anthocyanin synthesis pathway.
      The genomic sequence of the anthocyanidin synthase (ANS) gene in Brazilian yellow
      onions showed a point mutation, which results in an amino acid change of a
      glycine to an arginine at residue 229. Because this residue is located adjacent
      to a highly conserved iron-binding active site, this mutation is likely
      responsible for the inactivation of the ANS gene in Brazilian yellow onions.
      Following the isolation of the promoter sequence of the mutant allele, a PCR
      based marker for allelic selection of the ANS gene was designed. This assay is
      based on an insertion (larger than 3 kb) mutation. The marker perfectly co
      segregated with the color phenotypes in the F(2) populations, thereby indicating
      that the L locus encodes ANS.

PMID- 15856160
TI  - Genetic control of rice blast resistance in the durably resistant cultivar Gumei
      2 against multiple isolates.
AB  - To further our understanding of the genetic control of blast resistance in rice
      cultivar Gumei 2 and, consequently, to facilitate the utilization of this durably
      blast-resistant cultivar, we studied 304 recombinant inbred lines of indica rice
      cross Zhong 156/Gumei 2 and a linkage map comprising 181 markers. An analysis of
      segregation for resistance against five isolates of rice blast suggested that one
      gene cluster and three additional major genes that are independently inherited
      are responsible for the complete resistance of Gumei 2. The gene cluster was
      located to chromosome 6 and includes two genes mapped previously, Pi25(t),
      against Chinese rice blast isolate 92-183 (race ZC15) and Pi26(t) against
      Philippine rice blast isolate Ca89 (lineage 4), and a gene for resistance against
      Philippine rice blast isolate 92330-5 (lineage 17). Of the two genes conferring
      resistance against the Philippine isolates V86013 (lineage 15) and C923-39
      (lineage 46), we identified one as Pi26(t) and mapped the other onto the distal
      end of chromosome 2 where Pib is located. We used three components of partial
      blast resistance, percentage diseased leaf area (DLA), lesion number and lesion
      size, all measured in the greenhouse, to measure the degree of susceptibility to
      isolates Ca89 and C923-39 and subsequently identified nine and eight quantitative
      trait loci (QTLs), respectively. Epistasis was determined to play an important
      role in partial resistance against Ca89. Using DLA measured on lines susceptible
      in a blast nursery, we detected six QTLs. While different QTLs were detected for
      partial resistance to Ca89 and C923-39, respectively, most were involved in the
      partial resistance in the field. Our results suggest that the blast resistance in
      Gumei 2 is controlled by multiple major genes and minor genes with epistatic
      effects.

PMID- 15856161
TI  - [Injury patterns and typical stress situations in paragliding].
AB  - Paragliding is known as a high risk sport with a substantial rate of severe and
      fatal injuries. Analysis of typical injury mechanisms and statistics showed that
      the total rate of paragliding injuries has decreased in recent years for an
      increasing number of pilots. In 2003, the rate of severe and fatal injuries in
      paragliding was less than that of other air sports and motorcycling. Through the
      introduction of a spine protector system in Germany and Austria, the number of
      vertebral fractures decreased significantly between 2000 and 2003. Most other
      injuries, especially of the lower extremities, could be avoided by adequate and
      farsighted flight behavior. Qualified instruction with regular training,
      standardized development of safety equipment and consequent analysis of
      paragliding injuries will help to improve the safety status in paragliding.

PMID- 15856163
TI  - [Carving skiing].
AB  - At present there are approximately 4.2 million skiers in Germany with 82 million
      worldwide. The ski revolution of carving has been on its triumphant march
      worldwide for around 8 to 9 years. About 80% of all skiers now use carving skis
      and normal skis are hardly offered in the retail trade or by ski hire companies.
      The intense and controversial discussion of the past few years on the influence
      of carving for the risk of injuries in alpine skiing now appear to be answered.
      There has not been any increase in the risk of injuries. These results are
      confirmed by studies in other countries. In order to continue to reduce the
      number of skiing accidents, more attention should be paid to changes in the age
      structure of skiers and changes in skiing style owing to use of the carving ski,
      with measures for accident prevention. Specific physical preparation for the
      skiing season are more important than ever. Special attention must still be
      focused on observing FIS rules and general care.

PMID- 15856162
TI  - [Injury patterns and prophylaxis in inline skating].
AB  - Inline skating has become one of the fastest growing sports since its appearance
      in 1980. The increasing number of inline skaters has also led to a rising
      incidence of injuries. The most common injury is the distal fracture of the
      radius, which occurs in 50% of all fractures. There are several reasons for
      increasing serious injuries in inline skating. The majority of skaters do not
      wear proper protective equipment (helmet, elbow, knee and wrist protectors),
      however, many users can not handle their inline skates in dangerous situations.
      All skaters should take care by buying industrially tested inline skates and
      appropriate protective equipment; novice skaters should additionally attend
      special skating schools to learn skating, braking and the the correct falling
      techniques.

PMID- 15856164
TI  - [Mountain biking. Cool way to enjoy nature with side effects].
AB  - Mountain biking grew from a trend to a serious branch of sport. This article
      presents the different subspecialties within the sport, the injury rates and the
      types of injuries among high-class and recreational bikers. The experiences made
      during several years as a team physician of top athletes as well as the
      statistics from the Swiss accident insurance company SUVA are the basis for the
      data presented. The issue of mountain bike-related concussions is particularly
      discussed since this type of injury is a point of increasing concern in the
      recent sports traumatology literature.

PMID- 15856165
TI  - [Results of simple fragment excision in lumbar disc surgery].
AB  - BACKGROUND: While performing microsurgical disc excision, usually the
      sequestrated disc fragments as well as loosened or degenerated parts of the
      nucleus pulposus are removed. It is controversial whether this strategy is always
      necessary. The aim of this study was to examine this question based on clinical
      results. MATERIAL AND METHODS: Prospectively all relevant data from 149
      consecutive patients after sequestrectomy were collected including the clinical
      course of the patients with a mean follow-up of 2.3 years. A detailed analysis of
      the actual pain status, the functional capacity and possible additional spinal
      operations was performed. RESULTS: During early follow-up, there was one
      superficial wound infection, which was treated conservatively. The success rate,
      as measured by patient self-assessment, was 62% for excellent and good and 25%
      for fair results; 13% of the patients treated declared a poor result having no
      benefits from surgery. The average FFbH score during follow-up was 74% (100%
      means no functional restriction). Radicular pain and low back pain had the same
      intensity on the average, in contrast to some other investigations, where low
      back pain was lower than radicular pain [14]. Of the 149 patients, 4 underwent a
      second spine surgery at the same level, 2 of which were recurrent disc
      herniations (=1.3%). CONCLUSION: Simple fragment excision revealed similar
      results compared to standard microdiscectomy. There was an especially low number
      of recurrences in contrast to former reports [16]. This was probably caused by
      the conscientious selection of patients for sequestrectomy according to well
      defined criteria. Whether simple sequestrectomy can effectively treat an
      additional low back pain component must be clarified by further prospective
      studies.

PMID- 15856166
TI  - [Comparison of rheumatic and post-traumatic elbow joints after total elbow
      arthroplasty. Comprehensive and specific evaluation of clinical picture,
      function, and quality of life].
AB  - BACKGROUND: Patients with elbow destruction due to rheumatoid arthritis (RA) or
      trauma (PT) were compared to population-based normative data and to each other
      after total elbow arthroplasty. PATIENTS AND METHODS: Pain, function, and
      biopsychosocial health were multidimensionally assessed by the generic Short Form
      36 (SF-36), the condition-specific Disabilities of the Arm, Shoulder and Hand
      questionnaire (DASH), and the Patient Related Elbow Evaluation form (PREE)
      instrument and analyzed by uni- and multivariate methods. RESULTS: Compared to
      normative values, the examined 59 RA patients were significantly affected in the
      function scales of the SF-36 and in all DASH scales. The 20 PT patients were
      worse than the norm only in the DASH function. Function was lower in RA than in
      PT in the SF-36 scales and in the DASH (RA: 44.4, PT: 70.3, p<0.001). This
      difference was less distinct in the PREE. CONCLUSION: Total elbow arthroplasty
      led to a pain-free outcome and normal quality of life, but failed to restore
      complete function. Functional deficits were larger in the RA patients and could
      also be measured by the SF-36, possibly due to polyarticular affection.

PMID- 15856167
TI  - [PMMA pulmonary embolism and post interventional associated fractures after
      percutaneous vertebroplasty].
AB  - A 78-year old woman with osteoporotic collapse of the Th12 and L4 vertebrae was
      treated by percutaneous vertebroplasty (pVp) with PMMA (polymethylmethacrylate).
      Postoperatively, the Th11 and L1 vertebrae collapsed so that a second
      vertebroplasty was performed. Postoperatively, the patient developed a severe
      pulmonary embolism which was treated conservatively. In this report, the
      complications of pulmonary embolism, perivertebral leakage of PMMA and of
      additional vertebral collapses after pVp are discussed.

PMID- 15856168
TI  - End-of-life decisions: a cohort study of the withdrawal of all active treatment
      in intensive care units in the United Kingdom.
AB  - OBJECTIVE: To describe the epidemiology of active treatment withdrawal in a
      nationally representative cohort of intensive care units (ICUs) focusing on
      between-unit differences. DESIGN AND SETTING: Cohort study in 127 adult general
      ICUs in England, Wales and Northern Ireland, 1995 to 2001. PATIENTS: 118,199
      adult admissions to ICUs. MEASUREMENTS AND RESULTS: The decision to withdraw all
      active treatment was made for 11,694 of 118,199 patients (9.9%). There were a
      total of 36,397 deaths (30.8%) before discharge from hospital, and 11,586 (31.8%)
      of these occurred after the decision to withdraw active treatment, with no change
      over time (p=0.54). Considerable variation existed between units regarding the
      percentage of ICU deaths that occurred after the decision to withdraw active
      treatment (1.7-96.1%). Median time to death after the decision to withdraw active
      treatment was 2.4 h; 8% survived more than 24 h. After multilevel modelling, the
      factors independently associated with the decision to withdraw active treatment
      were: older age, pre-existing severe medical conditions, emergency surgery or
      medical admission, cardiopulmonary resuscitation in the 24 h prior to admission,
      and ventilation or sedation/paralysis in the first 24 h after admission.
      Substantial between unit variability remained after accounting for case-mix
      differences in admissions. CONCLUSIONS: Although we were unable to examine
      partial withdrawal or withholding of care in this study, we found that the
      withdrawal of all active treatment is widespread in ICUs in the United Kingdom.
      There was little change in this practice over the period examined. However, there
      was considerable variation by unit, even after accounting for patient factors and
      differences in size and type of ICU, suggesting improved guidelines may be useful
      to facilitate uniform decision making.

PMID- 15856169
TI  - Comment on "Mode of death after admission to an intensive care unit following
      cardiac arrest" by Laver et al.

PMID- 15856170
TI  - Survival in acute renal failure.

PMID- 15856171
TI  - Multicenter study of the multiple organ dysfunction syndrome in intensive care
      units: the usefulness of Sequential Organ Failure Assessment scores in decision
      making.
AB  - OBJECTIVE: This study examined the incidence and mortality of multiple organ
      dysfunction syndrome (MODS) in intensive care units, evaluated the limitation of
      life support in these patients, and determined whether daily measurement of the
      Sequential Organ Failure Assessment (SOFA) is useful for decision making. DESIGN
      AND SETTING: Prospective, observational study in 79 intensive care units.
      PATIENTS AND PARTICIPANTS: Of the 7,615 patients admitted during a 2-month period
      we found 1,340 patients to have MODS. MEASUREMENTS AND RESULTS: We recorded
      mortality and length of stay in the intensive care unit and the hospital and the
      maximum and minimum total SOFA scores during MODS. Limitation of life support in
      MODS patients was also evaluated. Stepwise logistic regression was used to
      determine the factors predicting mortality. The in-hospital mortality rate in
      patients with MODS was 44.6%, and some type of limitation of life support was
      applied in 70.6% of the patients who died. The predictive model maximizing
      specificity included the following variables: maximum SOFA score, minimum SOFA
      score, trend of the SOFA for 5 consecutive days, and age over 60 years. The model
      diagnostic yield was: specificity 100%, sensitivity 7.2%, positive predictive
      value 100%, and negative predictive value 57.3%; the area under the receiver
      operating characteristic curve was 0.807. CONCLUSIONS: This model showed that in
      our population with MODS those older than 60 years and with SOFA score higher
      than 9 for at least 5 days were unlikely to survive.

PMID- 15856172
TI  - Ventilator settings as a risk factor for acute respiratory distress syndrome in
      mechanically ventilated patients.
AB  - OBJECTIVE: A single-center retrospective study initial recently identified
      ventilator settings as a major risk factor for the development of acute
      respiratory distress syndrome (ARDS) in mechanically ventilated patients who do
      not have ARDS from the outset. We tested this hypothesis in a larger sample of
      patients prospectively enrolled in a multicenter study on mechanical ventilation.
      DESIGN AND SETTING: From a large international mechanical ventilation study
      database we identified patients who required mechanical ventilation for 48 h or
      more but did not have ARDS at the onset of mechanical ventilation. We extracted
      information on demographics, initial severity of illness, ventilator settings and
      major underlying ARDS risk factors. Primary outcome was development of ARDS after
      the onset of mechanical ventilation. MEASUREMENTS AND RESULTS: Of 3,261
      mechanically ventilated patients who did not have ARDS at the outset 205 (6.2%)
      developed ARDS 48 h or more after the onset of mechanical ventilation.
      Multivariate logistic regression analysis adjusted for baseline patient
      characteristics (age, gender, Simplified Acute Physiology Score, hypoxemia) and
      underlying ARDS risk factors (sepsis, trauma, pneumonia) found the development of
      ARDS to be associated with the initial ventilator settings: high tidal volume
      (odds ratio 2.6 for tidal volume>700 ml), high peak airway pressure (odds ratio
      1.6 for peak airway pressure>30 cmH2O), and high positive end-expiratory pressure
      (odds ratio 1.7 for end-expiratory pressure>5 cmH2O). CONCLUSIONS: The
      association with the potentially injurious initial ventilator settings, in
      particular large tidal volumes, suggests that ARDS in mechanically ventilated
      patients is in part a preventable complication. This hypothesis needs to be
      tested in a prospective study.

PMID- 15856173
TI  - Glass v United Kingdom and Burke v General Medical Council. Judicial
      interpretations of European Convention Rights for patients in the United Kingdom
      facing decisions about life-sustaining treatment limitations.

PMID- 15856174
TI  - Detrimental effect of sinusoidal overperfusion after liver resection and partial
      liver transplantation.
AB  - Liver resection exposes the remaining sinusoids to an over-proportional blood
      flow. This mechanism may aggravate ischaemia/reperfusion damage and rejection in
      partial liver transplants. We studied the potential relevance of this mechanism
      for the pathogenesis of partial liver transplant dysfunction. Eighty-four
      isogeneic Lewis rats were divided into four groups: (I) sham operation; (II)
      partial liver resection (30% residual liver volume); (III) orthotopic
      transplantation of a full-size liver; (IV) transplantation of a reduced-size
      liver (30% transplant volume). Microcirculation was determined by intravital
      microscopy 90 min after surgery. Survival rates, liver function and morphology
      were monitored over a period of 14 days. Lowest survival rates and impaired liver
      function were observed after partial liver transplantation (group IV). These
      transplants displayed the lowest perfusion rate and an increased rate of
      leukocyte-endothelium interactions in the presence of a significantly increased
      sinusoidal blood flow velocity compared with those in groups I and III.
      Sinusoidal overperfusion in groups II and IV resulted in widespread endothelium
      lesions. Sinusoidal overperfusion seems to be a significant factor impairing
      liver function after liver resection. In addition to other adverse factors, such
      as ischaemia/reperfusion injury, it can contribute to the pathogenesis of
      postoperative dysfunction of partial liver transplants.

PMID- 15856175
TI  - Effect of IGL-1, a new preservation solution, on kidney grafts (a pre-clinical
      study).
AB  - Ischemia-reperfusion injury conditions short-term and long-term graft function.
      The effects of the inversion of K+ and Na+ concentrations and substitution with
      polyethylene glycol for hydroxyethyl starch in University of Wisconsin (K-UW)
      solution were evaluated in isolated perfused rat kidneys and in autotransplanted
      pig kidneys. In the rat model kidneys were cold-stored for 24 h in K-UW or Na-UW
      or Na-PEG UW solutions (IGL-1 solution). Fractional sodium reabsorption and
      glomerular filtration rate was better in kidneys preserved in Na-UW and IGL-1
      solution than those preserved in K-UW solution. In the pig model the left kidney
      was harvested and preserved in K-UW or IGL-1 solution for 24 h and then
      transplanted. In the autotransplanted pig model, kidneys preserved in IGL-1
      solution showed a better function and a significant reduction of MHC class II
      expression, cellular apoptosis and interstitial fibrosis. In conclusion, kidneys
      preserved in IGL-1 solution tolerated ischemia/reperfusion injury better than
      those preserved in K-UW solution.

PMID- 15856176
TI  - Inadvertent cadaver kidney transplantation across the ABO barrier: a case report.

PMID- 15856177
TI  - The value of routine ophthalmological tests in the screening for lung
      transplantation.
AB  - We aimed to analyse the results of ophthalmological examinations in the screening
      before and in the follow-up after lung transplantation. Altogether, 295
      consecutive patients who had undergone ophthalmological examination in the
      screening before lung transplantation were analysed. Preoperatively 27% ocular
      abnormalities were found; none of them formed a contraindication for the
      transplantation. Of the 122 patients who underwent transplantation, 24 (20%) had
      postoperative ocular complaints. We can conclude that, because of the absence of
      contraindications in all of these patients, routine ophthalmological screening
      before transplantation is not recommended. Routine postoperative screening is not
      required, either.

PMID- 15856178
TI  - Requirement of a higher degree of chimerism for skin allograft tolerance in
      cyclophosphamide-induced tolerance.
AB  - By using a cyclophosphamide (CP)-induced tolerance system, we previously raised
      the possibility that the degree of chimerism might determine the induction of
      heart and skin allograft tolerance. When C3H (H-2k; Thy1.2, Mls-1b) mice were
      intravenously primed with 1 x 10(8) spleen cells (SCs) from H-2 matched AKR (H
      2k; Thy1.1, Mls-1a) mice and then treated intraperitoneally with 200 mg/kg CP,
      the survival of AKR skin grafts was permanently prolonged in a tolerogen-specific
      fashion. After this treatment, a minimal degree of mixed chimerism and the clonal
      destruction of Mls-1a-reactive CD4+Vbeta6+ T cells in the periphery were
      observed. When AKR SCs and 100 mg/kg CP were used for conditioning, the survival
      of the AKR skin grafts was mildly prolonged. The clonal destruction of
      CD4+Vbeta6+ T cells in the periphery was induced and a minimal degree of mixed
      chimerism was detectable. The degree of mixed chimerism induced with AKR SCs and
      200 mg/kg CP was significantly higher than that with AKR SCs and 100 mg/kg CP
      during the observation. On the other hand, neither skin allograft prolongation
      nor permanent mixed chimerism could be induced when C3H mice were treated with
      AKR SCs and 50 mg/kg CP. In order to increase the degree of mixed chimerism, we
      injected 1 x 10(8) tolerant AKR SCs on day 3 into the recipient C3H mice that had
      been treated with AKR SCs on day 0 and with 100 mg/kg CP on day 2. The reason
      that we used tolerant SCs was that untreated AKR SCs caused graft-versus-host
      disease in most of the recipients. Tolerant AKR SCs were harvested from AKR mice
      that had been treated with C3H SCs and 200 mg/kg CP 2 weeks earlier, and did not
      contain regulatory cells. By adoptive transfer, the degree of chimerism was
      stably and significantly increased in all recipients, and AKR skin graft
      tolerance was induced in half of the recipients. T-cell-depleted bone marrow
      cells (BMCs) from untreated AKR mice induced skin allograft tolerance in 83% of
      recipients. Thus, the present study strongly confirmed the hypothesis that a
      higher degree of chimerism is required for the induction of skin allograft
      tolerance in CP-induced tolerance.

PMID- 15856179
TI  - Arthroscopic treatment of osteochondritis dissecans of the capitellum.
AB  - The results of arthroscopic debridement and loose body retrieval for
      osteochondritis dissecans (OCD) of the capitellum in 29 symptomatic patients who
      had failed conservative management are described. There were no complications of
      surgery. At an average of 77 months after operation the majority of patients had
      mild or no pain but with some discomfort during heavy lifting and sport. All were
      capable of performing simple activities of daily living, and all but one had good
      or excellent outcomes and rated their satisfaction highly. Only 4 of 27 patients
      had to give up their preferred sport because of persistent elbow problems. Thirty
      eight percent of patients had recurrence of locking or catching, although these
      symptoms were described as better than the condition before operation and none
      wanted further surgical intervention. It is concluded that arthroscopic
      debridement and removal of loose bodies is a safe and reliable procedure for
      patients with persistent symptoms from OCD of the capitellum.

PMID- 15856180
TI  - Stress fracture of the olecranon in an adult baseball player.
AB  - Stress fractures of the olecranon caused by repetitive stress force have
      infrequently been reported as a cause of elbow pain in adult athletes, engaged in
      throwing and pitching sports. We diagnosed as a stress fracture of the olecranon
      by clinical and radiographic findings and treated surgically. The patient
      returned to playing baseball at a competitive level and was asymptomatic 4 months
      after the first operation. However, the patient re-injured the olecranon and a
      second surgical treatment was performed almost 1 year after the first operation.
      After the second surgery, the patient returned to playing baseball at a
      competitive level and was free from elbow symptoms. We presented a stress
      fracture of the olecranon in a semi-professional adult baseball player and
      suggested that surgical treatment is necessary.

PMID- 15856181
TI  - Effects of various man-made mineral fibers on cell apoptosis and viability.
AB  - Evaluating the pathogenic potentials of man-made mineral fibers (MMMF) is an
      important task performed by the European Community. Noting that it has been
      proposed that the use of laboratory animals for scientific tests should be
      reduced or phased out, macrophages then become the cells of choice for conducting
      in vitro studies. We have evaluated the in vitro toxicity of six commercial
      stonewool fibers (A, B1, B2, C, D, and E) on U-937 cells. The physical
      interaction between U-937 cells and MMMF was observed using scanning electron
      microscopy, and the cytotoxicity was evaluated by studying cell viability using
      MTT assay and cell apoptosis with an ELISA detection kit. Scanning electron
      microscopy (SEM) analysis has shown that long fibers can be covered by several
      macrophages, and that a small fiber can be completely engulfed by one cell. With
      50 microg/mL of MMMF, a decrease in cell viability appeared after seven days of
      incubation, whereas 200 microg/mL induced loss of viability and apoptosis after
      one day. Fiber D, comprising a high proportion of fibers >20 microm in length and
      a high concentration of MgO, induced the highest loss in viability and the
      highest rate of apoptosis compared to the other five fibers. Whether this toxic
      effect is related to either the physical characteristics of the fibers (such as
      length), or to the high concentration of magnesium is still to be determined.
      Because the results can be rapidly obtained, the proposed model is suitable for
      studying the toxicities of mineral components, even if the tested concentrations
      are far from the ones reached in the lung.

PMID- 15856182
TI  - Chemoprotective effects of captopril against cyclophosphamide-induced
      genotoxicity in mouse bone marrow cells.
AB  - The protective effects of captopril (CAP) against toxicity induced by
      cyclophosphamide (CP) in mice were investigated using the micronucleus assay for
      anticlastogenic activity in mouse bone marrow cells and liver glutathione (GSH)
      content. A single intraperitoneal (i.p.) injection of CAP at 50, 100, and 200
      mg/kg 1 h prior to cyclophosphamide (50 mg/kg) reduced the frequency of
      micronucleated polychromatic erythrocytes (MnPCEs). All three doses of CAP
      significantly reduced the frequency of MnPCEs in mouse bone marrow compared to
      the group treated with CP alone (P<0.0001-0.01). CP significantly depleted the
      GSH content in liver but the application of CAP at a dose of 100 mg/kg 1 h before
      CP treatment repleted the GSH content. CAP exhibited concentration-dependent
      antioxidant activity, scavenging >96% of the 1,1-diphenyl-2-picryl hydrazyl free
      radicals when used at a concentration of 0.2 mM. It appears that CAP, due to its
      antioxidant activity and by increasing GSH levels, can modulate the reduced
      cellular thiol content induced by CP and reduce the genotoxicity of CP in bone
      marrow cells.

PMID- 15856183
TI  - Nephrotoxicity of a novel antineoplastic platinum complex, nedaplatin: a
      comparative study with cisplatin in rats.
AB  - The present study was designed to characterize the nephrotoxicity induced by the
      antineoplastic platinum complex nedaplatin (NDP) in rats of different ages in
      comparison with cisplatin (CDDP). A single dose of 15 mg/kg NDP or 7.5 mg/kg CDDP
      was administered intravenously to 8-, 11-, or 15-week-old male and female SD
      rats, which were then sacrificed after ten days. Body weight decreases were
      observed for both drugs, in direct relation to age. CDDP treatment markedly
      increased urinary excretion of NAG, gamma-GTP, LDH and protein, with peaks on day
      4 and complete or partial recovery on day 7; NDP increased NAG, LDH and protein
      excretion, but to a lesser extent, and these elevations were generally more
      marked for females. CDDP increased plasma creatinine and BUN in males and females
      of all age groups at necropsy. No apparent changes were seen following NDP
      treatment except in the 15-week-old rats. These results also show that NDP is
      less nephrotoxic than CDDP. CDDP-treated rats showed remarkable proximal tubular
      lesions in the renal cortex and corticomedullary region, and the papillary
      lesions were minor. On the other hand, the NDP-induced nephrotoxicity was
      morphologically characterized by hyaline droplet changes (electron
      microscopically, hyperplasia of lysosomes), necrosis or hyperplasia of the
      collecting duct epithelium in the renal papilla and the epithelium covering the
      papilla. Cortical lesions, indicated by slight tubular dilatation, were found
      only in the animals with papillary lesions. In summary, NDP is a promising second
      generation platinum complex with reduced nephrotoxicity.

PMID- 15856184
TI  - Decreasing the oxidant stress from paraquat in isolated perfused rat lung using
      captopril and niacin.
AB  - The abilities of captopril and niacin to protect against the lung toxicity of
      paraquat (PQ) were studied. The anti-oxidative action of captopril, an
      angiotensin-converting enzyme inhibitor, appears to be attributable to the
      sulphahydryl group (SH) in the compound, which gives captopril the ability to
      scavenge reactive oxygen species. Niacin replenishes the NAD and ATP depletion
      caused by reactive oxygen species. PQ causes lung damage in man and in several
      species of laboratory animals. The damage is initially manifested by hemorrhage
      and edema, and later by consolidation of the lung and fibrosis development. In
      this study, the lungs of male Wistar rats (250-300 g in weight) were perfused by
      Krebs-Ringer buffer alone (control), niacin (150 microM), captopril (10 microM)
      and PQ (600 microM) in perfusion fluid, and the biochemical changes that occurred
      in isolated rat lung were examined within 1 h and compared to PQ alone. The
      results show that captopril significantly decreases the lung weight/body weight
      ratio when used as a pretreatment and a post-treatment to captopril (p<0.0001).
      The results also show that captopril (10 microM) and niacin (150 microM)
      significantly decreases PQ-induced lung toxicity. Lactate dehydrogenase (LDH)
      activity significantly decreased in treatment groups as compared to the PQ group
      (p<0.0001). This study suggests that paraquat causes increased lipid peroxidation
      and LDH activity and decreased glutathione (GSH) and total protein in isolated
      perfused rat lung. These effects are reduced under these experimental conditions
      by captopril and niacin.

PMID- 15856185
TI  - Effects of punishment on choice between cocaine and food in rhesus monkeys.
AB  - RATIONALE: Punishment is widely used in an effort to control drug-taking
      behavior; however, only a few preclinical studies have investigated the effects
      of punishment on drug self-administration. Such studies may contribute to more
      rational use of punishment to control drug use. OBJECTIVES: To evaluate the
      effects of punishment on choice between cocaine and food in rhesus monkeys.
      METHODS: Rhesus monkeys were trained under a concurrent-choice schedule of food
      delivery (1 g pellets, fixed-ratio 100 schedule) or cocaine injections (0-0.1
      mg/kg per injection, fixed-ratio 10 schedule). Full cocaine choice dose-effect
      curves were determined under baseline conditions and under test conditions in
      which a putative punisher (intravenous histamine injection; 0.0032-0.032 mg/kg
      per injection) was paired with either food or cocaine delivery. RESULTS: Under
      baseline conditions, cocaine produced a dose-dependent increase in cocaine
      choice. Histamine functioned as a punisher of both food- and cocaine-maintained
      responding. Pairing histamine with food delivery reduced food choice, increased
      cocaine choice, and produced left shifts in the cocaine choice dose-effect curve.
      Conversely, pairing histamine with cocaine decreased cocaine choice, increased
      food choice, and produced right shifts in the cocaine choice dose-effect curve.
      The magnitude of histamine's punishing effects was directly related to histamine
      dose and probability of histamine delivery, and inversely related to the
      magnitude of the reinforcer. CONCLUSIONS: These results demonstrate that a
      primary effect of punishment in the context of food vs cocaine choice is not only
      a decrease in the behavior being punished, but also an increase in the unpunished
      alternative behavior.

PMID- 15856186
TI  - Sensitization to amphetamine, but not phencyclidine, disrupts prepulse inhibition
      and latent inhibition.
AB  - RATIONALE: Schizophrenia has been linked to dysregulation of dopamine and
      glutamate transmitter systems. Attempts to model aspects of schizophrenia in
      animals have made use of treatments that primarily affect dopaminergic (e.g.,
      amphetamine, Amp) and glutamatergic (e.g., phencyclidine, PCP) function. In
      addition to exerting short-term acute effects, these agents also induce long-term
      effects, as seen, for example, in neurochemical and behavioural sensitization.
      OBJECTIVES: The goal of this work was to compare Amp- and PCP-sensitized states
      on two measures of information processing that are impaired in schizophrenia,
      prepulse inhibition (PPI) of the acoustic startle reflex and latent inhibition
      (LI). METHODS: Rats received injections of Amp, PCP or saline 3 days per week for
      3 weeks. The Amp dose increased from 1 to 3 mg/kg, at the rate of 1 mg/kg each
      week. The PCP dose was 3 mg/kg throughout. After various periods of withdrawal
      rats were tested for PPI and LI. RESULTS: Repeated intermittent treatment with
      Amp or PCP resulted in augmented locomotor responses to challenge with each drug,
      providing an operational index that sensitization had occurred. Rats sensitized
      to Amp showed disrupted PPI when tested drug free at 3, 21 and 60 days of
      withdrawal. Amp-sensitized rats also showed abolition of the LI effect. Rats
      sensitized to PCP did not show deficits in any of these behaviours when tested
      drug free. CONCLUSIONS: Because disrupted PPI and LI have both been reported in
      schizophrenic patients, these results suggest that the Amp-sensitized state may
      represent a useful model for investigating the neural bases of information
      processing deficits in schizophrenia.

PMID- 15856192
TI  - Classifying honeys from the Soria Province of Spain via multivariate analysis.
AB  - A total of 73 different honeys from seven botanical origins [ling (Calluna
      vulgaris L.), heather (Erica sp.), rosemary (Rosmarinus officinalis L.), thyme
      (Thymus vulgaris L.), honeydew (Quercus sp.), spike lavender (Lavandula latifolia
      M.) and french lavender (Lavandula stoechas L.)] have been classified by applying
      discriminant analysis to their metal content data and other common
      physicochemical parameters. Fifteen minerals were identified and quantified using
      atomic emission spectroscopy (AES) for K and Na, and inductively coupled plasma
      atomic emission spectrometry (ICP-AES) for Mg, Ca, Al, Fe, Mn, Zn, B, Cu, Co, Cr,
      Ni, Cd and Pb. Moreover, eight physicochemical parameters were analysed following
      the Harmonised Methods of the International Honey Commision: ash content,
      moisture, insoluble matter, reducing sugars, apparent sucrose, diastase activity,
      free acidity and hydroxymethylfurfural. The honeys analysed were characterised
      and distinguished using chemometrics. ANOVA highlighted significant differences
      between the honeys in terms of the mean contents of all variables except apparent
      sucrose, HMF, Fe and Zn. Principal component analysis was used as a descriptive
      tool to visualise the data structure in two dimensions, finding relationships
      between variables and types of honey. Likewise, discriminant analysis, together
      with various methods (stepwise, forward and backward), was used to select the
      variables with the highest discriminating power, which allowed us to classify all
      of the botanical origins considered in this work, achieving a global success rate
      close to 90% following cross-validation.

PMID- 15856195
TI  - Detection of 2,4,6-trichloroanisole in chlorinated water at nanogram per litre
      levels by SPME-GC-ECD.
AB  - A method involving solid-phase micro extraction (SPME) and gas chromatography
      with electron capture detection (SPME-GC-ECD) has been optimised for
      identification and quantification of 2,4,6-trichloroanisole (TCA) at ng L(-1)
      concentrations in disinfected (chlorinated) water samples. A central composite
      design was used for factorial analysis of four factors, three factors related to
      the SPME (PDMS fibre) procedure (adsorption time, temperature of the sample
      during headspace sampling, and desorption time) and one related to the GC
      operation (the rate of increase of the temperature of the GC oven). Good
      linearity (linear correlation coefficient greater than 0.999) was observed for
      TCA concentrations up to 50 ng L(-1), limits of detection and quantification of
      0.7 and 2.3 ng L(-1), respectively, and good precision (relative standard
      deviation 2.8% and 3.4% for 5 and 30 ng L(-1) of TCA, respectively). Besides TCA,
      this system also enables the detection and quantification of the four
      trihalomethanes in the microg L(-1) concentration range with limits of detection
      and quantification of approximately 0.3 microg L(-1) and 1 microg L(-1),
      respectively.

PMID- 15856197
TI  - A rapid and sensitive GC-MS method for determination of 1,3-dichloro-2-propanol
      in water.
AB  - A rapid analytical method for sensitive determination of 1,3-dichloro-2-propanol
      (1,3-DCP) in river water has been developed. 1,3-DCP is extracted from water with
      ethyl acetate. After filtration through sodium sulfate the ethyl acetate phase is
      analyzed by gas chromatography-mass spectrometry. The method uses 1,3-DCP-d5 as
      internal standard. Different extraction solvents, concentrations of ammonium
      sulfate in the water samples, and the effect of humic acid were tested and their
      influence on the recovery of DCP has been evaluated. The method quantification
      limit was 0.1 microg L(-1). For spiked water samples (0-5.2 microg L(-1), n=21) a
      repeatability coefficient of variation of 5.4% was obtained. The average recovery
      rate of 1,3-DCP was 105+/-3% (n=21). Stability tests, which were carried out with
      Danube river water, led to an estimated 1,3-DCP degradation rate of 0.008+/
      0.0008 day(-1) at 6 degrees C.

PMID- 15856198
TI  - Stereoselective peptide analysis.
AB  - The stereochemistry of a peptide determines its spatial features and can
      profoundly influence its chemical properties and biological activity. Thus, the
      analysis of the stereochemical properties of a peptide is an important aspect of
      its characterisation. For such investigations a "selector" that engages in
      stereoselective interactions with the peptide analytes is often used. A
      substantiated knowledge of the underlying molecular recognition mechanism will
      therefore be helpful in understanding existing and developing new stereoselective
      analysis systems. After a short introduction concerning the fundamentals of
      peptide stereoisomers and their biological implications, the stereoselective
      peptide analysis methods described in the literature are comprehensively
      reviewed. The characteristics and applications of the employed methods based on
      various techniques including chromatography (pressure- and electrokinetically
      driven), capillary electrophoresis, nuclear magnetic resonance spectroscopy and
      mass spectrometry are discussed. The various selectors that have been utilised to
      discriminate peptide enantiomers and/or diastereomers are described concurrently.
      The review concludes with an overview of combinations and comparisons of
      techniques that have been applied to the analysis of peptide stereoisomers and
      constitute a trend for further developments.

PMID- 15856199
TI  - A novel dynamic approach for automatic microsampling and continuous monitoring of
      metal ion release from soils exploiting a dedicated flow-through microdialyser.
AB  - In this paper, a novel concept is presented for automatic microsampling and
      continuous monitoring of metal ions in soils with minimum disturbance of the
      sampling site. It involves a hollow-fiber microdialyser that is implanted in the
      soil body as a miniaturized sensing device. The idea behind microdialysis in this
      application is to mimic the function of a passive sampler to predict the actual,
      rather than potential, mobility and bioavailability of metal traces. Although
      almost quantitative dialysis recoveries were obtained for lead (> or = 98%) from
      aqueous model solutions with sufficiently long capillaries (l > or = 30 mm, 200
      microm i.d.) at perfusion rates of 2.0 microL min(-1), the resistance of an inert
      soil matrix was found to reduce metal uptake by 30%. Preliminary investigation of
      the potential of the microdialysis analyser for risk assessment of soil
      pollution, and for metal partitioning studies, were performed by implanting the
      dedicated probe in a laboratory-made soil column and hyphenating it with
      electrothermal atomic absorption spectrometry (ETAAS), so that minute, well
      defined volumes of clean microdialysates were injected on-line into the graphite
      furnace. A noteworthy feature of the implanted microdialysis-based device is the
      capability to follow the kinetics of metal release under simulated natural
      scenarios or anthropogenic actions. An ancillary flow set-up was arranged in such
      a way that a continuous flow of leaching solution--mild extractant (10(-2) mol L(
      1) CaCl2), acidic solution (10(-3) mol L(-1) HNO3), or chelating agent (10(-4) or
      10(-2) mol L(-1) EDTA)--was maintained through the soil body, while the
      concentration trends of inorganic (un-bound) metal species at the soil-liquid
      interface could be monitored at near real-time. Hence, relevant qualitative and
      quantitative information about the various mobile fractions is obtained, and
      metal-soil phase associations can also be elucidated. Finally, stimulus-response
      schemes adapted from neurochemical applications and pharmacokinetic studies are
      to be extended to soil research as an alternative means of local monitoring of
      extraction processes after induction of a chemical change in the outer boundary
      of the permselective dialysis membrane.

PMID- 15856200
TI  - Does melatonin protect or treat brain damage from traumatic oxidative stress?
AB  - A variety of experimental studies have demonstrated the neuroprotective effects
      of melatonin, based on its antioxidant activity. In a prospective randomized
      study, the effects of melatonin were investigated in experimental head trauma
      induced oxidative stress in rabbits. The experimental study was performed on 30
      rabbits. The animals were divided into three groups. Group I (sham procedure): a
      right parietal craniotomy was performed on each animal, and the dura mater was
      left intact. Group II: experimental brain trauma (EBT) was performed on each
      animal using a 1 cm inner diameter x 10 cm long glass tube, through which a 20 g
      weight (0.5 cm diameter) was dropped onto the brain at the craniotomy site,
      causing a contusional head trauma. Group III: the same EBT model was performed,
      but 2.5 mg/kg melatonin was injected intraperitoneally four times (total dose 10
      mg/kg); these injections were performed 20 min before the operation, during the
      trauma, 1 h later and 2 h later. The rabbits were sacrificed after the EBT at 24
      h after the brain trauma. The activities of the three principal antioxidant
      enzymes-catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase
      (GSH-Px)-were determined, and the levels of malondialdehyde (MDA), a product of
      lipid peroxidation, and glutathione (GSH) were measured in brain homogenates. MDA
      levels were found to be higher in the EBT group than in the EBT+melatonin group
      or the sham procedure group. The SOD activity was found to be higher in the EBT
      group than in the sham procedure group. Enzymatic parameters (except for SOD)
      were significantly higher in melatonin-treated animals than in EBT animals. GSH
      levels in melatonin-treated animals were decreased compared with EBT animals. In
      conclusion, the data indicate that melatonin protects against free radical
      mediated oxidative changes in brain tissue by boosting antioxidant enzymes, and
      in particular lowering lipid peroxidation in rabbits with EBT.

PMID- 15856201
TI  - Changes in the centrifugal gating effect on somatosensory evoked potentials
      depending on the level of contractile force.
AB  - In this study, we investigated the somatosensory evoked potentials (SEPs) during
      the preparatory period of self-initiated plantar flexion at different force
      levels of muscle contraction and elucidated the mechanism behind the centrifugal
      gating effect on somatosensory information processing. We recorded SEPs following
      stimulation of the tibial nerve at the popliteal fossa during the preparatory
      period of a 20% maximal voluntary contraction (MVC) and 50% MVC. The preparatory
      period was divided into two sub-periods based on the components of movement
      related cortical potentials, the negative slope (NS sub-period) and the
      Bereitschaftspotential (BP sub-period). The subjects were instructed to
      concentrate on the movement and not to pay attention to the continuous electrical
      stimulation. Pre-movement SEPs were averaged separately during the two sub
      periods under each MVC condition. The mean amplitudes of BP and NS were larger
      during the 50% MVC than the 20% MVC. As for the components of SEPs, during the NS
      sub-period the amplitude of P30 under the 50% MVC and N40 under both conditions
      were significantly smaller than that in the stationary sequence, and N40
      amplitude was significantly smaller during the 50% MVC than the 20% MVC. During
      the BP sub-period, the amplitude of P30 and N40 during the 50% MVC was
      significantly smaller than during the stationary sequence, while it was not
      significantly different between the 20% and 50% MVCs. In conclusion, the extent
      of the centrifugal gating effect on SEPs was dependent on the activities of motor
      related areas, which generated the NS and BP.

PMID- 15856202
TI  - Interference between velocity-dependent and position-dependent force-fields
      indicates that tasks depending on different kinematic parameters compete for
      motor working memory.
AB  - Humans demonstrate motor learning when exposed to changes in the dynamics of
      movement or changes in the visuomotor map. However, when two opposing dynamic
      transformations are learned in succession, the memory of the first is overwritten
      by learning of the second; the same is true for two opposing visuomotor
      rotations. This retrograde interference is not seen for all combinations of
      transformations, however. When a dynamic transformation is learned subsequent to
      a visuomotor rotation, the presence or absence of interference appears to depend
      crucially on the structure of the dynamic task: a force-field dependent on the
      position of the hand produces interference, whereas an inertial load applied
      lateral to the hand does not. To explain these results, it has been hypothesized
      that two transformations can be learned without interference if they depend on
      two different kinematic parameters of movement (such as position and velocity of
      the hand). Here we demonstrate, contrary to this hypothesis, interference between
      a dynamic transformation that depends on the position of the hand and one that
      depends on its velocity. However, the interference was found to be incomplete,
      supporting the view that the ability to retain motor memories for different tasks
      depends on the degree to which their representations conflict in working memory.

PMID- 15856203
TI  - Head stabilization on a continuously oscillating platform: the effect of a
      proprioceptive disturbance on the balancing strategy.
AB  - When standing and balancing on a continuously and predictably moving platform,
      body equilibrium relies on both anticipatory control and proprioceptive feedback.
      We have vibrated different postural muscles of the body to assess any effect of
      confounding the proprioceptive input on balance during such unstable conditions.
      Low and high platform oscillation frequencies were used, because different
      strategies are used to withstand the two perturbations. Eyes open (EO) and closed
      (EC) conditions were also tested, to assess whether the stabilizing effect of
      vision is independent from the proprioceptive disturbance. Subjects (n = 14)
      performed two series of trials, EO and EC: (1) quiet erect stance, (2) stance on
      the platform translating at 0.2 or 0.6 Hz sinusoidally in the anteroposterior (A
      P) direction (dynamic conditions). Continuous bilateral vibration (90 Hz) was
      produced by two vibrators fixed to the following homonymous muscles: dorsal neck,
      quadriceps, biceps femoris, tibialis anterior, and triceps surae. Acquisition of
      body segments' displacement began 10 s after the start of platform translation.
      From markers fixed to head, hip, and malleolus, we computed the A-P oscillation
      of head and hip, body orientation in space, and cross-correlation (CC) and time
      delay between malleolus and head trajectories. The results were (a) the head A-P
      oscillation was smaller with EO than EC, under both quiet stance and dynamic
      conditions; (b) vibration of tibialis and triceps surae, but not of other
      muscles, slightly increased head and body A-P oscillation with EC under dynamic
      conditions; (c) at 0.2 Hz but not at 0.6 Hz, for all visual and vibration
      conditions, there was a significant association between head and feet; (d) at 0.2
      Hz, EC, neck muscle vibration increased this association, whereas vibration of
      the other muscles induced a major time delay in the oscillation of head compared
      with feet; (e) vibration of either neck or tibialis induced forward body leaning,
      while vibration of either triceps surae or biceps femoris induced backward
      leaning, with both EO and EC, under both static and dynamic conditions; (f) the
      head A-P oscillation, however, under dynamic conditions was not dependent on body
      leaning. The relatively scarce effects of proprioceptive disturbance on head
      stabilization and multijoint coordination (in spite of effects on body
      orientation similar to those observed during stance) speak for a major role of
      anticipatory control in the dynamic equilibrium task. However, the significant
      vibration-induced time delay in segments' coordination at low translation
      frequency, EC, suggests that the normally patterned Ia input promotes continuous
      adjustments of the feed-forward control mode.

PMID- 15856204
TI  - Novel strategies in feedforward adaptation to a position-dependent perturbation.
AB  - To investigate the control mechanisms used in adapting to position-dependent
      forces, subjects performed 150 horizontal reaching movements over 25 cm in the
      presence of a position-dependent parabolic force field (PF). The PF acted only
      over the first 10 cm of the movement. On every fifth trial, a virtual mechanical
      guide (double wall) constrained subjects to move along a straight-line path
      between the start and target positions. Its purpose was to register lateral force
      to track formation of an internal model of the force field, and to look for
      evidence of possible alternative adaptive strategies. The force field produced a
      force to the right, which initially caused subjects to deviate in that direction.
      They reacted by producing deviations to the left, "into" the force field, as
      early as the second trial. Further adaptation resulted in rapid exponential
      reduction of kinematic error in the latter portion of the movement, where the
      greatest perturbation to the handpath was initially observed, whereas there was
      little modification of the handpath in the region where the PF was active.
      Significant force directed to counteract the PF was measured on the first guided
      trial, and was modified during the first half of the learning set. The total
      force impulse in the region of the PF increased throughout the learning trials,
      but it always remained less than that produced by the PF. The force profile did
      not resemble a mirror image of the PF in that it tended to be more trapezoidal
      than parabolic in shape. As in previous studies of force-field adaptation, we
      found that changes in muscle activation involved a general increase in the
      activity of all muscles, which increased arm stiffness, and selectively-greater
      increases in the activation of muscles which counteracted the PF. With training,
      activation was exponentially reduced, albeit more slowly than kinematic error.
      Progressive changes in kinematics and EMG occurred predominantly in the region of
      the workspace beyond the force field. We suggest that constraints on muscle
      mechanics limit the ability of the central nervous system to employ an inverse
      dynamics model to nullify impulse-like forces by generating mirror-image forces.
      Consequently, subjects adopted a strategy of slightly overcompensating for the
      first half of the force field, then allowing the force field to push them in the
      opposite direction. Muscle activity patterns in the region beyond the boundary of
      the force field were subsequently adjusted because of the relatively-slow
      response of the second-order mechanics of muscle impedance to the force impulse.

PMID- 15856205
TI  - Prenatal alcohol exposure alters the size, but not the pattern, of the whisker
      representation in neonatal rat barrel cortex.
AB  - Maternal alcohol exposure results in a variety of neurodevelopmental
      abnormalities that include cognitive and sensorimotor dysfunctions that often
      persist into adulthood. Many reports of central nervous system disturbances
      associated within a clinical diagnosis of fetal alcohol syndrome point toward
      disturbances in central information processing. In this study, we used the rat
      barrel field cortex as a model system to examine the effects of prenatal alcohol
      exposure (PAE) on the organization and size of the large whisker representation
      in layer IV of the posteromedial barrel subfield (PMBSF) in somatosensory cortex.
      Pregnant rats (Sprague-Dawley) were intragastrically gavaged daily with alcohol
      doses (6 gm/kg body weight) from gestational day 1 to day 20 in a chronic binge
      pattern which produced blood alcohol levels ranging between 260 mg/dl and 324
      mg/dl. Chow-fed (CF), pair-fed (PF), and cross-foster (XF) groups served as
      normal, nutritionally matched, and maternal controls, respectively, for the
      ethanol-exposed (EtOH) treatment group. All pups were examined on gestational day
      32 corresponding approximately to postnatal day 9. EtOH and control group pups
      were weighed, anesthetized, and perfused. Brains were removed and weighed, with
      and without cerebellum and olfactory bulbs, and the neocortex was removed and
      weighed. Cortices were then flattened, sectioned tangentially, and stained with a
      metabolic marker-cytochrome oxidase-to reveal the barrel field. A subset of 27
      cortical barrels, associated with the representation of the large whisker pad,
      was selected to examine in detail. The major results were: (i) the total barrel
      field area comprising the PMBSF was significantly reduced in EtOH (by 17%) and XF
      (by 16%) pups compared with CF pups, (ii) the sizes of individual barrels within
      the PMBSF were also significantly reduced in EtOH (16%) and XF (18%) pups, (iii)
      the septal region between barrels was also significantly reduced in EtOH (18%)
      and XF (12%) pups, (iv) anteriorly located barrels underwent greater reduction in
      size relative to the posteriorly located barrels, (v) body weights were also
      significantly reduced in EtOH (21%) and XF (27%) pups, (vi) total brain weight
      [with and without (forebrain) cerebellum/olfactory bulbs] and cortical weights
      were also significantly reduced in EtOH (total brain weight 15%, forebrain weight
      16%, cortical weight 15%) and XF (18%, 19%, 20%) pups, and in contrast (vi)
      neither the overall barrel field pattern nor the pattern of individual barrels in
      the PMBSF was altered. These findings suggest that PAE reduces body and brain
      weight as well as the central cortical representation of the whisker pad, while
      leaving the overall barrel field pattern unperturbed. While these results might
      appear to support a miniaturization hypothesis (smaller PMBSF, smaller brain,
      smaller body weight), PAE also shows regional vulnerability within the PMBSF
      whereby anteriorly located barrels are most affected.

PMID- 15856206
TI  - Influence of biomechanical factors on substructure of pointing movements.
AB  - Irregularities in the velocity profile near the end of pointing movements have
      been interpreted as corrective submovements whose purpose is to provide accuracy
      of pointing to the target. The purpose of the present study was to investigate
      whether two additional factors related to biomechanical properties of the arm
      also cause submovements. First, motion termination and stabilization of the limb
      in the final position required by a discrete pointing task may contribute to
      submovements. Second, inaccurate regulation of interactive torque at the joints
      may also cause submovements. To investigate the contributions of these two
      biomechanical factors and the traditionally considered factor of pointing
      accuracy, the incidence of submovements was analyzed during three types of
      experimental manipulations. In addition to target size manipulations (small and
      large targets), conditions for motion termination were manipulated by examining
      discrete movements (which terminated at the target) and reciprocal movements
      (which reversed direction without dwelling on the target). Interaction torques
      were varied by using targets that require different shoulder-elbow coordination
      patterns. Submovements were detected in 41% of all analyzed movements. Data
      supported influences from the accuracy and motion termination factors but not
      from the interactive torque regulation factor on submovement incidence. Gross
      submovements were associated with motion termination; fine submovements primarily
      with accuracy demands. These findings and the analysis of temporal movement
      characteristics suggest that motion termination is an extra movement component
      that makes control of discrete movements different to control of reciprocal
      movements. Implications of the findings to a noise-related interpretation of
      Fitts' law are discussed. The study emphasizes the influence of arm biomechanics
      on endpoint kinematics.

PMID- 15856207
TI  - Perceived motion direction during smooth pursuit eye movements.
AB  - Although many studies have been devoted to motion perception during smooth
      pursuit eye movements, relatively little attention has been paid to the question
      of whether the compensation for the effects of these eye movements is the same
      across different stimulus directions. The few studies that have addressed this
      issue provide conflicting conclusions. We measured the perceived motion direction
      of a stimulus dot during horizontal ocular pursuit for stimulus directions
      spanning the entire range of 360 degrees. The stimulus moved at either 3 or 8
      degrees/s. Constancy of the degree of compensation was assessed by fitting the
      classical linear model of motion perception during pursuit. According to this
      model, the perceived velocity is the result of adding an eye movement signal that
      estimates the eye velocity to the retinal signal that estimates the retinal image
      velocity for a given stimulus object. The perceived direction depends on the gain
      ratio of the two signals, which is assumed to be constant across stimulus
      directions. The model provided a good fit to the data, suggesting that
      compensation is indeed constant across stimulus direction. Moreover, the gain
      ratio was lower for the higher stimulus speed, explaining differences in results
      in the literature.

PMID- 15856208
TI  - Proprioceptive feedback in humans expresses motor invariants during writing.
AB  - Proprioceptive feedback from populations of muscle spindle afferents feeds the
      brain with information relating to the instantaneous velocity and direction of
      ongoing movements. In this paper, we investigate whether the invariant
      relationship between the velocity and curvature of a trajectory, i.e. the two
      thirds power law, is reflected in this muscle spindle feedback. Sixty unitary
      muscle spindle afferents from six ankle muscle groups were recorded using
      intraneural microelectrodes during imposed "writing-like" movements. The
      movements had kinematic parameters obeying the two-thirds power law and were
      imposed so that the tip of the foot followed trajectories forming four different
      letters and six numbers. The responses of the muscle spindle afferent populations
      were analysed using the population vector model. The results demonstrate that the
      neuronal trajectories attained from populations of muscle spindles clearly depict
      the path and kinematic parameters and express the movement invariants, i.e. the
      trajectory segmentation into units of action and the two-thirds power law. The
      central vs peripheral origin of such constraints involved in the motor system is
      discussed.

PMID- 15856209
TI  - Basic elements of arm postural control analyzed by unloading.
AB  - To address the question of how arm posture is controlled, we analyzed shoulder
      elbow unloading responses in the horizontal plane for different directions of the
      initial load. The initial load, produced by a double-joint manipulandum, was
      suddenly diminished to 1of 12 randomly presented levels (60 to -10% of the
      initial load; in 6 out of 12 cases the final load direction varied by +/-20
      degrees ). Subjects were instructed "not to intervene" in response to unloading.
      Neither the unloading onset nor the final load level was predictable and we
      assumed that the responses to rapid unloading were involuntary. Unloading
      elicited a smooth hand movement characterized by a bell-shaped velocity profile.
      The changes in hand position, joint angles, and joint torques generally increased
      with greater amounts of unloading. For each direction of the initial load, tonic
      electromyographic activity of the shoulder and elbow muscles also changed,
      depending on the amount of unloading. The shoulder and elbow joint torques before
      and after unloading were a function of the difference between the actual
      configuration of the arm and its referent configuration (R) described by the
      angles at which each joint torque was zero. The R configuration changed depending
      on the direction of the initial load. Our electromyographic data imply that these
      changes result from a central modification of muscle activation thresholds. The
      nervous system may thus control the R configuration in a task-specific way by
      leaving it unchanged to generate involuntary responses to unloading or modifying
      it to accommodate a new load direction at the same initial position. It is
      concluded that the R configuration is a major variable in both intentional and
      involuntary control of posture.

PMID- 15856210
TI  - Decreased anxiety levels related to aging.
AB  - The present experiment investigated the effects of aging on emotional behavior,
      without concomitant influences from any previous behavioral manipulation apart
      from weighing the rats. Anxiety-related behaviors were measured in the elevated
      plus-maze (EPM). Performance in the open field (OF) was also assessed to control
      for any effect of aging on exploratory behavior that could account for changes in
      emotional behavior. Fifty-two naive male Wistar rats of 3 (3MO), 17 (17MO), or 24
      (24MO) months, were submitted to two sessions (5 min each) of EPM, followed by
      two sessions (2 min each) of OF, on 4 consecutive days. The main emotional
      indices (open arm entries, ratio of open arm entries to total entries, time spent
      in open arms, ratio of time in open arms to time in four arms, open arm ends, and
      head dips) measured in the EPM indicated a lower level of anxiety in aged (24MO)
      than in young (3MO) rats, whereas middle-aged (17MO) rats showed intermediate
      values between those of 3MO and 24MO rats; 3MO rats showed higher general motor
      activity (number of rearings in closed arms of EPM and in OF, and higher number
      of areas crossed in OF) than 17MO and 24MO rats. We conclude that aging is
      associated with a decrease in anxiety and in general motor activity.

PMID- 15856211
TI  - Co-induction of alphaB-crystallin and MAPKAPK-2 in astrocytes in the penumbra
      after transient focal cerebral ischemia.
AB  - alphaB-crystallin (alpha-BC), a member of the small heat-shock proteins (sHSP),
      is constitutively expressed in the vertebrate lens and in non-ocular tissues
      including the central nervous system (CNS). In this study we investigated the
      expression of alpha-BC in the rat brain after middle cerebral artery occlusion
      (MCAO). alpha-BC transcript and protein were transiently expressed 4 h after
      MCAO/reperfusion in the pyramidal neurons in the peri-infarct region of the
      ischemic hemisphere. Beginning 2 days after MCAO, significant alpha-BC induction
      appeared in reactive astrocytes in the penumbra, and this induction was sustained
      for several days. In addition, levels of MAPKAPK-2, one of the alpha-BC upstream
      kinases, and its phosphorylated form were upregulated gradually and peaked 4 days
      after ischemia/reperfusion injury. The immunohistochemical study indicated that
      alpha-BC was co-localized with MAPKAPK-2 and p-MAPKAPK-2. Furthermore, p38beta
      MAPK, an upstream kinase of MAPKAPK-2, which has been known to be involved in
      compensatory responses to stress, was also co-localized with alpha-BC in the
      penumbra. Our results suggest that the p38beta-dependent alpha-BC induction in
      neurons and astrocytes in the penumbra may play an important role in the
      postischemic brain.

PMID- 15856212
TI  - Perceiving a stable world during active rotational and translational head
      movements.
AB  - When a person moves through the world, the associated visual displacement of the
      environment in the opposite direction is not usually seen as external movement
      but rather as a changing view of a stable world. We measured the amount of visual
      motion that can be tolerated as compatible with the perception of moving within a
      stable world during active, sinusoidal, translational and rotational head
      movement. Head movements were monitored by means of a low-latency, mechanical
      head tracker and the information was used to update a helmet-mounted visual
      display. A variable gain was introduced between the head tracker and the display.
      Ten subjects adjusted this gain until the visual display appeared stable during
      sinusoidal yaw, pitch and roll head rotations and naso-occipital, inter-aural and
      dorso-ventral translations at 0.5 Hz. Each head movement was tested with movement
      either orthogonal to or parallel with gravity. A wide spread of gains was
      accepted as stable (0.8 to 1.4 for rotation and 1.1 to 1.8 for translation). The
      gain most likely to be perceived as stable was greater than that required by the
      geometry (1.2 for rotation; 1.4 for translation). For rotational motion, the mean
      gains were the same for all axes. For translation there was no effect of whether
      the movement was inter-aural (mean gain 1.6) or dorso-ventral (mean gain 1.5) and
      no effect of the relative orientation of the translation direction relative to
      gravity. However translation in the naso-occipital direction was associated with
      more closely veridical settings (mean gain 1.1) and narrower standard deviations
      than in other directions. These findings are discussed in terms of visual and non
      visual contributions to the perception of an earth-stable environment during
      active head movement.

PMID- 15856213
TI  - Three-dimensional reconstruction and volumetry of intracranial haemorrhage and
      its mass effect.
AB  - Intracerebral haemorrhage still causes considerable disability and mortality. The
      studies on conservative and operative management are inconclusive, probably due
      to inexact volumetry of the haemorrhage. We investigated whether three
      dimensional (3-D), voxel-based volumetry of the haemorrhage and its mass effect
      is feasible with routine computed tomography (CT) scans. The volumes of the
      haemorrhage, ventricles, midline shift, the intracranial volume and ventricular
      compression in CT scans of 12 patients with basal ganglia haemorrhage were
      determined with the 3-D slicer software. Indices of haemorrhage and intracranial
      or ventricular volume were calculated and correlated with the clinical data. The
      intended measures could be determined with an acceptable intra-individual
      variability. The 3-D volumetric data tended to correlate better with the clinical
      course than the conventionally assessed distance of midline shift and volume of
      haemorrhage. 3-D volumetry of intracranial haemorrhage and its mass effect is
      feasible with routine CT examination. Prospective studies should assess its value
      for clinical studies on intracranial space-occupying diseases.

PMID- 15856214
TI  - Monitoring of regional cerebral oxygenation by near-infrared spectroscopy in
      carotid arterial stenting: preliminary study.
AB  - In carotid arterial stenting (CAS), ischemic complications and cerebral
      hyperperfusion are recognized as devastating complications. To detect these
      complications in early stages, we assessed the feasibility for real-time
      measurement of regional oxygen saturation (rSO2) of the brain in 24 patients with
      symptomatic extracranial carotid artery stenosis in CAS. The rSO2 changes were
      easy to evaluate and significantly correlated with the ischemic neurological
      symptoms as well as postoperative hyperperfusion detected by single-photon
      emission computed tomography (SPECT). Moreover, the pattern of changes in rSO2
      was significantly correlated with the asymmetry index and the cerebral
      vasoreactivity examined by preoperative SPECT. Therefore, simultaneous monitoring
      of rSO2 is feasible in detecting early hemodynamic complications in CAS.

PMID- 15856215
TI  - Diffuse choroid plexus hyperplasia: an under-diagnosed cause of hydrocephalus in
      children?
AB  - Hydrocephalus is a common neurological disorder in children and the result of a
      variety of causes. However, with the advancement of imaging modalities,
      particularly MRI, previously reported rarer causes of hydrocephalus in children
      are now being more readily appreciated. We report an 11-year-old boy with diffuse
      villous hyperplasia of the choroid plexus. He had a ventriculo-peritoneal (VP)
      shunt in-situ and a prior diagnosis from infancy of congenital aqueduct stenosis
      as the cause of his hydrocephalus. His current presentation was with further
      shunt dysfunction. CT and MRI demonstrated enlarged choroid plexuses but did not
      confirm aqueduct stenosis. CSF overproduction was demonstrated from the
      externalized ventricular drain. The enlarged choroid plexuses were surgically
      resected and histology confirmed choroid plexus hyperplasia. Identification of
      choroid plexus hyperplasia is important since the neurosurgical management of
      hydrocephalus is not VP shunt insertion, but resection of the hyperplastic
      choroid plexus.

PMID- 15856216
TI  - Osmotic stability of the cell membrane of Escherichia coli from a temperature
      limited fed-batch process.
AB  - The temperature-limited fed-batch (TLFB) process is a technique where the oxygen
      consumption rate is controlled by a gradually declining temperature profile
      rather than a growth-limiting glucose-feeding profile. In Escherichia coli
      cultures, it has been proven to prevent an extensive release of endotoxins, i.e.
      lipopolysaccharides, that occurs in the glucose-limited fed-batch (GLFB)
      processes at specific growth rates below 0.1 h(-1). The TLFB and the GLFB process
      were compared to each other when applied to produce the periplasmic,
      constitutively expressed, enzyme beta-lactamase. The extraction of the enzyme was
      performed by osmotic shock. A higher production of beta-lactamase was achieved
      with the TLFB technique while no difference in the endotoxin release was found
      during the extraction procedure. Furthermore, it was found that growth at
      declining temperature, generated by the TLFB technique, gradually stabilizes the
      cytoplasmic membrane, resulting in a significantly increased product quality in
      the extract from the TLFB cultures in the osmotic shock treatment.

PMID- 15856217
TI  - Large plasmid pCAR2 and class II transposon Tn4676 are functional mobile genetic
      elements to distribute the carbazole/dioxin-degradative car gene cluster in
      different bacteria.
AB  - The carbazole-catabolic plasmid pCAR1 isolated from Pseudomonas resinovorans
      strain CA10 was sequenced in its entirety; and it was found that pCAR1 carries
      the class II transposon Tn4676 containing carbazole-degradative genes. In this
      study, a new plasmid designated pCAR2 was isolated from P. putida strain HS01
      that was a transconjugant from mating between the carbazole-degrader Pseudomonas
      sp. strain K23 and P. putida strain DS1. Southern hybridization and nucleotide
      sequence analysis of pCAR1 and pCAR2 revealed that the whole backbone structure
      was very similar in each. Plasmid pCAR2 was self-transmissible, because it was
      transferred from strain HS01 to P. fluorescens strain IAM12022 at the frequency
      of 2 x 10(-7) per recipient cell. After the serial transfer of strain HS01 on
      rich medium, we detected the transposition of Tn4676 from pCAR2 to the HS01
      chromosome. The chromosome-located copy of Tn4676 was flanked by a 6-bp target
      duplication, 5'-AACATC-3'. These results experimentally demonstrated the
      transferability of pCAR2 and the functionality of Tn4676 on pCAR2. It was clearly
      shown that plasmid pCAR2 and transposon Tn4676 are active mobile genetic elements
      that can mediate the horizontal transfer of genes for the catabolism of
      carbazole.

PMID- 15856218
TI  - Adaptation of Rhodococcus erythropolis DCL14 to growth on n-alkanes, alcohols and
      terpenes.
AB  - Rhodococcus erythropolis DCL14 has the ability to convert the terpene (-)-carveol
      to the valuable flavour compound (-)-carvone when growing on a wide range of
      carbon sources. To study the effect of carbon and energy sources such as alkanes,
      alkanols and terpenes on the biotechnological process, the cellular adaptation at
      the level of fatty acid composition of the membrane phospholipids and the (-)
      carvone production were examined. All tested carbon sources caused a dose
      dependent increase in the degree of saturation of the fatty acids. The exception
      was observed with short-chain alcohols such as methanol and ethanol, to which the
      cells adapted with a concentration-dependent decrease in the saturation degree of
      the membrane phospholipids. This influence of the different carbon sources on the
      rigidity of the cell membrane also had an impact on the (-)-carvone productivity
      of the strain.

PMID- 15856219
TI  - Transcriptome analysis of the secretion stress response of Bacillus subtilis.
AB  - Transcription profiling of all protein-encoding genes of Bacillus subtilis was
      carried out under several secretion stress conditions in the exponential growth
      phase. Cells that secreted AmyQ alpha-amylase at a high level were stressed only
      moderately: seven genes were induced, most significantly htrA and htrB, encoding
      quality control proteases, and yqxL, encoding a putative CorA-type Mg(2+)
      transporter. These three genes were induced more strongly by severe secretion
      stress (prsA3 mutant secreting AmyQ), suggesting that their expression responds
      to protein misfolding. In addition, 17 other genes were induced, including the
      liaIHGFSR (yvqIHGFEC) operon, csaA and ffh, encoding chaperones involved in the
      pretranslocational phase of secretion, and genes involved in cell wall
      synthesis/modification. Severe secretion stress caused downregulation of 23
      genes, including the prsA paralogue yacD. Analysis of a cssS knockout mutant
      indicated that the absence of the CssRS two-component system, and consequently
      the absence of the HtrA and HtrB proteases, caused secretion stress. The results
      also suggest that the htrA and htrB genes comprise the CssRS regulon. B. subtilis
      cells respond to secretion/folding stress by various changes in gene expression,
      which can be seen as an attempt to combat the stress condition.

PMID- 15856220
TI  - Fungal biotransformation of benzo[f]quinoline, benzo[h]quinoline, and
      phenanthridine.
AB  - Cultures of Umbelopsis ramanniana (=Mucor ramannianus) were grown in fluid
      Sabouraud medium for 3 days, dosed with 0.23 mM benzo[f]quinoline,
      benzo[h]quinoline, or phenanthridine (benzo[c]quinoline), and incubated for
      another 18 days. Cultures were extracted and metabolites (66-75% of the UV
      absorbance) were separated by high-performance liquid chromatography. They were
      identified by mass spectrometry and nuclear magnetic resonance spectroscopy.
      Benzo[f]quinoline was metabolized to benzo[f]quinoline trans-7,8-dihydrodiol,
      benzo[f]quinoline N-oxide, and 7-hydroxybenzo[f]quinoline, benzo[h]quinoline was
      metabolized to benzo[h]quinoline trans-5,6-dihydrodiol, benzo[h]quinoline trans
      7,8-dihydrodiol, and 7-hydroxybenzo[h]quinoline, and phenanthridine was
      metabolized to phenanthridine N-oxide and phenanthridin-6(5H)-one. At least one
      of the metabolites produced from each compound was mutagenic and could not be
      considered detoxified.

PMID- 15856221
TI  - Identification of regulatory polymorphisms in the TNF-TNF receptor superfamily.
AB  - The tumor necrosis factor and TNF receptor (TNF-TNFR) superfamily plays very
      important roles in the pathogenesis of many immune-mediated diseases. Regulation
      of TNF-TNFR superfamily gene expression influences many aspects of the pathology
      associated with these diseases. In order to investigate genetic variations in the
      regulatory regions of the TNF-TNFR superfamily genes, promoter regions were
      screened by sequencing DNA samples from 24 unrelated Korean individuals. We
      identified a total of 68 single-nucleotide polymorphisms (SNPs) in the regulatory
      regions of the known TNF-TNFR superfamily genes, including 50 SNPs in the
      promoter regions, 16 SNPs in the 5'-UTR regions, and two SNPs in the coding
      regions of these genes. Among the 68 SNPs identified in this study, 25 SNPs were
      novel SNPs. Interestingly, the sequence alteration created by 11 SNPs completely
      abolished putative transcription factor binding sites in these alleles. These
      results suggest that these SNP sites can regulate gene expression by controlling
      the binding of transcription factors. The identification of function-altering
      SNPs in the promoter regions of the TNF-TNFR superfamily will facilitate efforts
      to understand the association of TNF-TNFR superfamily genes with several immune
      mediated human diseases.

PMID- 15856222
TI  - Expression of porcine lactoferrin by using recombinant baculovirus in silkworm,
      Bombyx mori L., and its purification and characterization.
AB  - Lactoferrin is a multifunctional glycoprotein that is present in several mucosal
      secretions. In this study, we exploited the silkworm, Bombyx mori, as host for
      the recombinant baculovirus harboring the porcine lactoferrin (PLF) gene to
      produce the recombinant PLF (rPLF). Around 205 mug of rPLF was purified from a
      single silkworm pupa infected by the virus and the rPLF was proved to be
      biologically active. This method established in our study will pave the way for
      efficient industrial production of rPLF on a large scale for further utilization
      of this protein as a feed additive in the future.

PMID- 15856223
TI  - Modeling of growth kinetics for Pseudomonas spp. during benzene degradation.
AB  - A modeling study was conducted on growth kinetics of three different strains of
      Pseudomonas spp. (Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas
      putida) during benzene degradation to determine optimum substrate concentrations
      for most efficient biodegradation. Batch tests were performed for eight different
      initial substrate concentrations to observe cell growth and associated substrate
      degradation using benzene-adapted cells. Kinetic parameters of both inhibitory
      (Haldane-Andrews, Aiba-Edwards) and noninhibitory (Monod) models were fitted to
      the relationship between specific growth rate and substrate concentration
      obtained from the growth curves. Results showed that half-saturation constant of
      P. fluorescens was the highest among the three strains, indicating that this
      strain could grow well at high concentration, while P. putida could grow best at
      low concentration. The inhibition constant of P. aeruginosa was the highest,
      implying that it could tolerate high benzene concentration and therefore could
      grow at a wider concentration range. Estimated specific growth rate of P. putida
      was lower, but half-saturation constant was higher than those from literature
      study due to high substrate concentration range used in this study. These two
      kinetic parameters resulted in substantial difference between Monod- and Haldane
      type models, indicating that distinction should be made in applying those models.

PMID- 15856224
TI  - The use of genetically modified Saccharomyces cerevisiae strains in the wine
      industry.
AB  - In recent decades, science and food technology have contributed at an accelerated
      rate to the introduction of new products to satisfy nutritional, socio-economic
      and quality requirements. With the emergence of modern molecular genetics, the
      industrial importance of Saccharomyces cerevisiae, is continuously extended. The
      demand for suitable genetically modified (GM) S. cerevisiae strains for the
      biofuel, bakery and beverage industries or for the production of biotechnological
      products (e.g. enzymes, pharmaceutical products) will continuously grow in the
      future. Numerous specialised S. cerevisiae wine strains were obtained in recent
      years, possessing a wide range of optimised or novel oenological properties,
      capable of satisfying the demanding nature of modern winemaking practise. The
      unlocking of transcriptome, proteome and metabolome complexities will contribute
      decisively to the knowledge about the genetic make-up of commercial yeast strains
      and will influence wine strain improvement via genetic engineering. The most
      relevant advances regarding the importance and implications of the use of GM
      yeast strains in the wine industry are discussed in this mini-review. In this
      work, various aspects are considered including the strategies used for the
      construction of strains with respect to current legislation requirements, the
      environmental risk evaluations concerning the deliberate release of genetically
      modified yeast strains, the methods for detection of recombinant DNA and protein
      that are currently under evaluation, and the reasons behind the critical public
      perception towards the application of such strains.

PMID- 15856225
TI  - Utilization of keratin-containing biowaste to produce biohydrogen.
AB  - A two-stage fermentation system was constructed to test and demonstrate the
      feasibility of biohydrogen generation from keratin-rich biowaste. We isolated a
      novel aerobic Bacillus strain (Bacillus licheniformis KK1) that displays
      outstanding keratinolytic activity. The isolated strain was employed to convert
      keratin-containing biowaste into a fermentation product that is rich in amino
      acids and peptides. The process was optimized for the second fermentation step,
      in which the product of keratin fermentation--supplemented with essential
      minerals--was metabolized by Thermococcus litoralis, an anaerobic
      hyperthermophilic archaeon. T. litoralis grew on the keratin hydrolysate and
      produced hydrogen gas as a physiological fermentation byproduct.
      Hyperthermophilic cells utilized the keratin hydrolysate in a similar way as
      their standard nutrient, i.e., bacto-peptone. The generalization of the findings
      to protein-rich waste treatment and production of biohydrogen is discussed and
      possible means of further improvements are listed.

PMID- 15856226
TI  - TNT and nitroaromatic compounds are chemoattractants for Burkholderia cepacia R34
      and Burkholderia sp. strain DNT.
AB  - Nitroaromatic compounds are toxic and potential carcinogens. In this study, a
      drop assay was used to detect chemotaxis toward nitroaromatic compounds for wild
      type Burkholderia cepacia R34, wild-type Burkholderia sp. strain DNT, and a 2,4
      dinitrotoluene (2,4-DNT) dioxygenase mutant strain (S5). The three strains are
      chemotactic toward 2,4,6-trinitrotoluene (TNT), 2,3-DNT, 2,4-DNT, 2,5-DNT, 2
      nitrotoluene (NT), 4NT, and 4-methyl-5-nitrocatechol (4M5NC), but not toward 2,6
      DNT. Of these, only 2,4-DNT is a carbon and energy source for B. cepacia R34 and
      Burkholderia sp. strain DNT, and 4M5NC is an intermediate in the 2,4-DNT
      degradation pathway. It was determined that the 2,4-DNT dioxygenase genes are not
      required for the chemotaxis for these nitroaromatic compounds because the DNT DDO
      mutant S5 has a chemotactic response toward 2,4-DNT although 2,4-DNT is not
      metabolized by S5; hence, 2,4-DNT itself is the chemoattractant. This is the
      first report of chemotaxis toward TNT, 2,3-DNT, 2,4-DNT, 2,5-DNT, 2NT, 4NT, and
      4M5NC.

PMID- 15856227
TI  - Characterization of biochemical properties and biological activities of
      biosurfactants produced by Pseudomonas aeruginosa mucoid and non-mucoid strains
      isolated from hydrocarbon-contaminated soil samples.
AB  - Biochemical and pharmacological properties of biosurfactants produced at 45
      degrees C temperature by Pseudomonas aeruginosa mucoid (M) and non-mucoid (NM)
      strains, isolated from hydrocarbon-contaminated soil samples, were characterized.
      Both the strains secreted appreciable amount of biosurfactants (5.0-6.5 g/l),
      responsible for the reduction of surface tension of the medium from 68 to 29 +/-
      0.5 mN/m post 96 h of growth. Maximum yield of biosurfactants was observed
      following the supplementation of NH(4)Cl and glycerol as nitrogenous source and
      carbon source, respectively. These thermostable biosurfactants exhibited strong
      emulsifying property and could release appreciable amount of oil from saturated
      sand-pack column. Pharmacological characterization of these biosurfactants
      revealed that they induced dose-dependent hemolysis and coagulation of platelet
      poor plasma but were non-detrimental to chicken lung, liver, heart and kidney
      tissues. Our study has documented that biosurfactants from P. aeruginosa M and NM
      strains could be exploited for use in petroleum sectors as well in pharmaceutical
      industries.

PMID- 15856228
TI  - Antiangiogenic chimeric anti-endoglin (CD105) antibody: pharmacokinetics and
      immunogenicity in nonhuman primates and effects of doxorubicin.
AB  - We generated a human/mouse chimeric antibody c-SN6j of human IgG1 isotype from a
      murine anti-human endoglin (EDG) monoclonal antibody (mAb) SN6j that suppressed
      angiogenesis, tumor growth and metastasis in mice. We determined pharmacokinetics
      (PKs) and immunogenicity of c-SN6j in monkeys after multiple i.v. injections. A
      dose-escalation study was performed by administration of c-SN6j into six monkeys
      at the dose of 1 mg, 3 mg and 10 mg per kg body weight. In addition, both c-SN6j
      (3 mg/kg) and doxorubicin (0.275 mg/kg) were injected into two monkeys. c-SN6j
      and doxorubicin were injected twice a week for 3 weeks. We developed a unique and
      sensitive ELISA by sequentially targeting the common and idiotypic epitopes of c
      SN6j-Fv to quantify plasma c-SN6j. Application of the ELISA showed that
      increasing the c-SN6j dose resulted in a proportional increase in the circulating
      c-SN6j after the first injection. In addition, the estimated area under the curve
      (AUC) for the first injection of c-SN6j is proportional to dose. We carried out
      detailed analyses of PKs of c-SN6j during and after the repeated injections. Our
      model of PKs fitted the empirical data well. Addition of doxorubicin modulated
      the PK parameters. We developed two ELISAs to separately determine the immune
      responses to the murine part and the human part of c-SN6j in monkeys.
      Interestingly, the murine part induced a weaker immune response than the human
      part. Doxorubicin potentiated the immune responses. Increasing the dose of c-SN6j
      increased plasma levels of c-SN6j but did not increase the immune responses to c
      SN6j.

PMID- 15856229
TI  - Increased body mass index is a predisposition for treatment by total hip
      replacement.
AB  - We investigated the radiological and epidemiological data of 4,151 subjects
      followed up from 1976 to 2003 to determine individual risk factors for hip
      osteoarthritis (OA), hip pain and/or treatment by total hip replacement (THR).
      Pelvic radiographs recorded in 1992 were assessed for evidence of hip-joint
      degeneration and dysplasia. Sequential body mass index (BMI) measurements from
      1976 to 1992, age, exposure to daily lifting and hip dysplasia were entered into
      logistic regression analyses. The prevalence of hip dysplasia ranged from 5.4% to
      12.8% depending on the radiographical index used. Radiological hip OA prevalence
      was 1.0--2.5% in subjects <60 years of age and 4.4--5.3% in subjects >or=60 years
      of age. While radiological OA was significantly influenced by hip dysplasia in
      men and hip dysplasia and age in women, the risk of THR being performed was only
      influenced by BMI assessed in 1976. Hip-joint degeneration and treatment by THR
      do not necessarily share the same risk factors, and caution should be exercised
      in epidemiological studies in attributing one or the other as the end point of
      coxarthrosis.

PMID- 15856230
TI  - Resurfacing hip prostheses revisited: failure analysis during a 16-year follow
      up.
AB  - We conducted a prospective study of the clinical and radiographic variables
      related to the survival of 114 cementless resurfacing double-cup hip replacements
      (RHR) with a mean follow-up of 9 (range: 1--16) years. Three patients died, and
      22 were unavailable for the final review in 2003. Sixty-one RHRs had to be
      revised to a total hip replacement. Failure analysis of these revised RHRs showed
      femoral head and neck resorption under the prosthesis in 33, acetabular
      protrusion in seven, both femoral and acetabular resorption in 14 and a femoral
      neck fracture in three. One hip had dislocated, and there were three hips with
      unexplained pain. The Kaplan-Meier 5-year mean survival was 92%, the 10-year
      survival was 47% (95% CI 37--57%) and the 15-year survival was 30% (95% CI 20-
      40%). Pre-operative joint destruction (grade 1), a high degree of radiological
      osteoporosis, a body mass index >25 and prosthesis mismatch were significantly
      related to failure of the RHR. We believe that in young, non-obese patients with
      pre-operative radiological central destruction but without severe proximal
      femoral osteoporosis, a resurfacing arthroplasty may have some value. Our
      failures were mainly due to femoral resorption under the prosthetic femoral
      component.

PMID- 15856231
TI  - P450 induction alters paclitaxel pharmacokinetics and tissue distribution with
      multiple dosing.
AB  - PURPOSE: Paclitaxel (Taxol) is an effective agent against a broad range of human
      cancers. Studies on the metabolism and disposition of paclitaxel have shown that
      it is primarily eliminated via hepatic metabolism by P450 enzymes (2C8 and 3A4)
      to essentially inactive metabolites, and that biliary and gut transport by P
      glycoprotein (PGP) as well as urinary elimination of the parent compound play
      relatively minor roles. Recent studies in vitro have shown that paclitaxel
      treatment increases the level of CYP2C8 and CYP3A4 in human hepatocytes as well
      as PGP in colon tumor cells. The data suggest that previous paclitaxel exposure
      may influence metabolism and elimination of subsequent doses. Further, since
      weekly paclitaxel dose schedules are becoming more common as opposed to the
      original every 21-day dosing, the likelihood of enzyme induction from previous
      doses impacting that from subsequent doses is increased. METHODS: To study the
      potential for such sequence-dependent alterations in paclitaxel pharmacokinetics,
      we carried out pharmacokinetic studies in mouse plasma and tissues following day
      1 and days 1 and 5 dosing at 20 mg/kg. Paclitaxel concentrations were determined
      by a sensitive LC/MS/MS assay out to 16 h post-dosing in plasma, liver, kidney,
      gut and heart. The effect of paclitaxel treatment on hepatic expression of PGP
      and P450 isoforms (CYP2C and CYP3A) was determined to elucidate the mechanism by
      which paclitaxel disposition is altered by previous drug exposure. RESULTS:
      Pharmacokinetic analysis of the data showed that plasma and tissue AUC values
      after treatment on day 5 following a dose on day 1 were between 50% and 74% of
      those determined following a single dose on day 1. The terminal elimination half
      life was not different. Activity and protein levels for CYP2C in liver were
      elevated at 24 and 96 h after paclitaxel dosing. Cremophor EL, a carrier solvent
      for paclitaxel, also caused elevated CYP2C activity. Neither CYP3A nor PGP levels
      in liver were altered by paclitaxel or Cremophor EL treatment at the 24-h and 96
      h time points. The levels of 6alpha-OH-paclitaxel in feces were increased on day
      5 as opposed to day 1 while paclitaxel levels in feces were unchanged.
      CONCLUSIONS: The results of our studies showed that paclitaxel pharmacokinetics
      are altered by previous paclitaxel exposure up to 96 h earlier.

PMID- 15856232
TI  - Structure-activity relationships of antineoplastic ring-substituted ether
      phospholipid derivatives.
AB  - PURPOSE: Previous studies have shown that alkylphosphocholines (APCs) exhibit
      strong antineoplastic activity against various tumour cell lines in vitro and in
      several animal models. The current study was designed to investigate the
      influence of cycloalkane rings on the antiproliferative activity of APCs against
      a panel of eight human and animal cell lines (PC3, MCF7, A431, Hela, PC12, U937,
      K562, CHO). Specifically, we explored the effect of the presence of 4
      alkylidenecyclohexyl and cycloalkylidene groups in alkoxyethyl and
      alkoxyphosphodiester ether lipids, respectively. In addition, the haemolytic
      activity of the new ring-substituted ether phospholipids (EP) was evaluated.
      METHODS: Cells were exposed to various concentrations of the compounds for 72 h.
      The cytotoxicity was determined with the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide] dye reduction assay. Similarly, red blood cells were
      distributed in 96-well microplates and treated with the test compounds at
      concentrations ranging from 100 to 6.25 microM for 1 h. After centrifugation, the
      absorbance of the supernatants was measured at 550 nm. RESULTS: The majority of
      the compounds tested exhibited significant cytotoxic activity which depended on
      both the ring size and position with respect to the phosphate moiety, as well as
      the head group. Among the cycloalkylidene series the 11-adamantylideneundecyl
      substituted N-methylmorpholino EP 13 was the most potent and exhibited broad
      spectrum anticancer activity comparable to or superior to that of
      hexadecylphosphocholine (HePC). All the adamantylidene-substituted EPs were
      nonhaemolytic (concentration that exhibits 50% haemolytic activity, HC(50), >100
      microM). Furthermore, the cyclohexylidene-substituted analogues were more potent
      against the cell lines tested, with the exception of U937 and K562, than the
      cyclodecapentylidene-substituted compounds. Hydrogenation of the double bond in
      the cycloalkylidene-substituted EPs (compounds 14 and 15) resulted in improvement
      of anticancer activity. Among the 2-(4-alkylidenecyclohexyloxy)ethyl EPs, 2-(4
      hexadylidenecyclohexyloxy)ethyl phosphocholine (22) possessed the highest broad
      spectrum cytotoxic activity than all the other analogues of this series and was
      nonhaemolytic (HC(50) >100 microM). In general, the 2-(4
      alkylidenecyclohexyloxy)ethyl-substituted EPs were more active against the more
      resistant cell lines U937, K562 and CHO than HePC. CONCLUSIONS: The presence of
      cycloalkane rings in the lipid portion of APCs reduces haemolytic effects
      compared to HePC and in several analogues results in improved antineoplastic
      activity.

PMID- 15856233
TI  - Sequence effect of docetaxel and carboplatin on toxicity, tumor response and
      pharmacokinetics in non-small-cell lung cancer patients: a phase I study of two
      sequences.
AB  - PURPOSE: To investigate sequence effects on toxicity, tumor response and
      pharmacokinetics of docetaxel and carboplatin, together with a determination of
      the maximum-tolerated dose (MTD) and recommended dose for each schedule. PATIENTS
      AND METHODS: A total of 46 chemotherapy-naive patients with advanced non-small
      cell lung cancer were randomized to receive docetaxel before (schedule A) or
      after (schedule B) carboplatin. The dose levels studied were [docetaxel
      (mg/m(2))/carboplatin (mg x min/ml)] 50/5, 60/5, 60/6, 60/7, and 70/6. Treatment
      cycles were repeated every 3 or 4 weeks unless disease progression or undue
      toxicity occurred. RESULTS: Of the 46 patients, 44 were assessable for toxicity
      and received a total of 84 cycles. The major dose-limiting toxicity was
      neutropenia. When the docetaxel dose was 60 mg/m(2), the carboplatin MTD was
      deemed to be AUC 7 in both schedules. When the docetaxel dose was escalated to 70
      mg/m(2), the carboplatin MTD was reached in schedule A, and the dose-limiting
      toxicity was not observed in schedule B. Tumor response was observed in 4 of 22
      patients (18%) with schedule A and 8 of 19 (42%) with schedule B. Clearances of
      both drugs were not affected by sequence: 111.2+/-26.8 ml/min and 107.8+/-29.0
      ml/min for carboplatin (P=0.69), and 26.7+/-8.3 l/h and 22.8+/-7.0 l/h for
      docetaxel (P=0.19) in schedules A and B, respectively. CONCLUSIONS: Carboplatin
      AUC 6 followed by docetaxel 70 mg/m(2) was a favorable regimen for phase II study
      because of likely lower toxicity and a potentially higher response rate than the
      reverse sequence schedule. The mechanism of the sequence effects on toxicity and
      tumor response could not be explained by the pharmacokinetic interactions.

PMID- 15856234
TI  - Peroxidases have more functions than a Swiss army knife.
AB  - Plant peroxidases (class III peroxidases) are present in all land plants. They
      are members of a large multigenic family. Probably due to this high number of
      isoforms, and to a very heterogeneous regulation of their expression, plant
      peroxidases are involved in a broad range of physiological processes all along
      the plant life cycle. Due to two possible catalytic cycles, peroxidative and
      hydroxylic, peroxidases can generate reactive oxygen species (ROS) (*OH, HOO*),
      polymerise cell wall compounds, and regulate H2O2 levels. By modulating their
      activity and expression following internal and external stimuli, peroxidases are
      prevalent at every stage of plant growth, including the demands that the plant
      meets in stressful conditions. These multifunctional enzymes can build a rigid
      wall or produce ROS to make it more flexible; they can prevent biological and
      chemical attacks by raising physical barriers or by counterattacking with a large
      production of ROS; they can be involved in a more peaceful symbiosis. They are
      finally present from the first hours of a plant's life until its last moments.
      Although some functions look paradoxical, the whole process is probably regulated
      by a fine-tuning that has yet to be elucidated. This review will discuss the
      factors that can influence this delicate balance.

PMID- 15856235
TI  - Towards normalization of soybean somatic embryo maturation.
AB  - Soybean (Glycine max L. Merrill) somatic embryos have been useful for assaying
      seed-specific traits prior to plant recovery. Such traits could be assessed more
      accurately if somatic embryos more closely mimicked seed development. Amino acid
      supplements, carbon source, and abscisic acid and basal salt formulations were
      tested in an effort to modify existing soybean embryogenesis
      histodifferentiation/maturation media to further normalize the development of
      soybean somatic embryos. The resultant liquid medium, referred to as soybean
      histodifferentiation and maturation medium (SHaM), consists of FNL basal salts,
      3% sucrose, 3% sorbitol, filter-sterilized 30 mM glutamine and 1 mM methionine.
      SHaM-derived somatic embryos are more similar to seed in terms of protein and
      fatty acid/lipid composition, and conversion ability, than somatic embryos
      obtained from traditional soybean histodifferentiation and maturation media.

PMID- 15856236
TI  - 1H chemical shift imaging, MRI, and diffusion-weighted imaging in vanishing white
      matter disease.

PMID- 15856237
TI  - Assessment of cortical maturation with prenatal MRI. Part I: Normal cortical
      maturation.
AB  - Cortical maturation, especially gyral formation, follows a temporospatial
      schedule and is a good marker of fetal maturation. Although ultrasonography is
      still the imaging method of choice to evaluate fetal anatomy, MRI has an
      increasingly important role in the detection of brain abnormalities, especially
      of cortical development. Knowledge of MRI techniques in utero with the advantages
      and disadvantages of some sequences is necessary, in order to try to optimize the
      different magnetic resonance sequences to be able to make an early diagnosis. The
      different steps of cortical maturation known from histology represent the
      background necessary for the understanding of maturation in order to be then able
      to evaluate brain maturation through neuroimaging. Illustrations of the normal
      cortical maturation are given for each step accessible to MRI for both the
      cerebral hemispheres and the posterior fossa.

PMID- 15856238
TI  - Endovascular obliteration of bleeding duodenal varices in patients with liver
      cirrhosis.
AB  - The purpose of this paper is to describe our experience with endovascular
      obliteration of duodenal varices in patients with liver cirrhosis and portal
      hypertension. Balloon-occluded transvenous retrograde and percutaneous
      transhepatic anterograde embolizations were performed for duodenal varices in
      five patients with liver cirrhosis, portal hypertension, and decreased liver
      function. All patients had undergone previous endoscopic treatments that failed
      to stop bleeding and were poor surgical candidates. Temporary balloon occlusion
      catheters were used to achieve accumulation of an ethanolamine oleate-iopamidol
      mixture inside the varices. Elimination of the varices was successful in all
      patients. Retrograde transvenous obliteration via efferent veins to the inferior
      vena cava was enough to achieve adequate sclerosant accumulation in three
      patients. A combined anterograde-retrograde embolization was used in one patient
      with balloon occlusion of afferent and efferent veins. Transhepatic embolization
      through the afferent vein was performed in one patient under balloon occlusion of
      both efferent and afferent veins. There was complete variceal thrombosis and no
      bleeding was observed at follow-up. No major complications were recorded.
      Endovascular obliteration of duodenal varices is a feasible and safe alternative
      procedure for managing patients with portal hypertension and hemorrhage from this
      source.

PMID- 15856239
TI  - Ipsilateral mamillary body atrophy after infarction of the posterior cerebral
      artery territory: MR imaging.
AB  - We describe herein magnetic resonance (MR) features of ipsilateral mamillary body
      atrophy after infarction of the posterior cerebral artery (PCA) territory. During
      the period May 2000 through July 2004, 13 patients with infarction of the PCA
      territory underwent cranial MR imaging in the chronic stage. Two 1.5-T scanners
      were used to obtain axial T1- and T2-weighted images with conventional spin-echo
      and fast spin-echo pulse sequences, respectively. The slice thickness was 6 mm,
      with a 2-mm interslice gap. Five of the 13 patients with PCA territory infarction
      had ipsilateral mamillary body atrophy. However, this asymmetry of the mamillary
      bodies was unclear in two of the five patients because of the thickness of the
      axial image slices. All five patients had a temporo-parieto-occipital infarction.
      The remaining eight patients had a parieto-occipital or an occipital infarction.
      Unilateral transneuronal mamillary body degeneration after infarction of the
      ipsilateral PCA territory including the posteromedial temporal lobe can be
      detected on conventional thick axial MR images.

PMID- 15856240
TI  - Two-dimensional and three-dimensional oxygen mapping by 3He-MRI validation in a
      lung phantom.
AB  - The aim of this study was to validate oxygen-sensitive 3He-MRI in noninvasive
      determination of the regional, two- and three-dimensional distribution of oxygen
      partial pressure. In a gas-filled elastic silicon ventilation bag used as a lung
      phantom, oxygen sensitive two- and three-dimensional 3He-MRI measurements were
      performed at different oxygen concentrations which had been equilibrated in a
      range of normal and pathologic values. The oxygen partial pressure distribution
      was determined from 3He-MRI using newly developed software allowing for mapping
      of oxygen partial pressure. The reference bulk oxygen partial pressure inside the
      phantom was measured by conventional respiratory gas analysis. In two-dimensional
      measurements, image-based and gas-analysis results correlated with r=0.98; in
      three-dimensional measurements the between-methods correlation coefficient was
      r=0.89. The signal-to-noise ratio of three-dimensional measurements was about
      half of that of two-dimensional measurements and became critical (below 3) in
      some data sets. Oxygen-sensitive 3He-MRI allows for noninvasive determination of
      the two- and three-dimensional distribution of oxygen partial pressure in gas
      filled airspaces.

PMID- 15856241
TI  - Cervical spine and crystal-associated diseases: imaging findings.
AB  - The cervical spine may be specifically involved in crystal-associated
      arthropathies. In this article, we focus on the three common crystals and
      diseases: hydroxyapatite crystal deposition disease, calcium pyrophosphate
      dihydrate (CPPD) deposition disease, and monosodium urate crystals (gout). The
      cervical involvement in crystal-associated diseases may provoke a misleading
      clinical presentation with acute neck pain, fever, or neurological symptoms.
      Imaging allows an accurate diagnosis in typical cases with calcific deposits and
      destructive lesions of the discs and joints. Most of the cases are related to
      CPPD or hydroxyapatite crystal deposition; gout is much less common.

PMID- 15856242
TI  - Reducing dose in urography while maintaining image quality-a comparison of
      storage phosphor plates and a flat-panel detector.
AB  - The introduction of new flat-panel detector technology often forces us to accept
      too high dose levels as proposed by the manufacturers. We need a tool to compare
      the image quality of a new system with the accepted standard. The aim of this
      study was to obtain a comparable image quality for two systems-storage phosphor
      plates and a flat-panel system using intravenous urography (IVU) as a clinical
      model. The image quality figure was calculated using a contrast-detail phantom
      (CDRAD) for the two evaluated systems. This allowed us to set a dose for the flat
      panel system that gave equivalent image quality to the storage phosphor plates.
      This reduced detector dose was used in an evaluation of clinical images to find
      out if the dose reduction from the phantom study indeed resulted in images of
      equal clinical image quality. The image quality was assessed using image criteria
      of the European guidelines for IVU with visual grading analysis. Equivalent image
      quality in image pairs was achieved at 30% of the dose. The CDRAD contrast-detail
      phantom makes it possible to find dose levels that give equal image quality using
      different imaging systems.

PMID- 15856243
TI  - Computed tomography angiography versus digital subtraction angiography in
      vascular mapping for planning of microsurgical reconstruction of the mandible.
AB  - The aim of this work was to compare the potential of computed tomography
      angiography (CTA) with that of digital subtraction angiography (DSA) in vascular
      mapping of the external carotid artery (ECA) branches for planning of
      microvascular reconstructions of the mandible with osteomyocutaneous flaps. In 15
      patients CTA and DSA were performed prior to surgery. Selective common carotid
      angiograms were acquired in two projection for both sides of the neck. Sixteen
      slice spiral computed tomography was performed with a dual-phase protocol, using
      the arterial phase images for 3D CTA reconstruction. Thin-slab maximum intensity
      projections and volume rendering were employed for postprocessing of CTA data.
      The detectability of the different ECA branches in CTA and DSA was evaluated by
      two examiners. No statistically significant differences between CTA and DSA
      (p=0.097) were found for identifying branches relevant for microsurgery. DSA was
      superior to CTA if more peripheral ECA branches were included (P=0.030). CTA
      proved to be a promising alternative to DSA in vascular mapping for planning of
      microvascular reconstruction of the mandible.

PMID- 15856244
TI  - Magnetic resonance signal alterations in the acute onset of heterotopic
      ossification in patients with spinal cord injury.
AB  - The purpose of our study was to evaluate magnetic resonance (MR) signal
      characteristics of acutely forming heterotopic ossification (HO) in paralyzed
      patients. Fourteen patients with spinal cord injury (female n=2, male n=12, mean
      age 38.3 years) and acute onset of radiographically proven HO had contrast
      enhanced 1.5-T MRI within 13.4+/-18.3 days of clinical onset of symptoms. MR
      signal alterations of affected muscles, fascia, subcutaneous tissue, skin and
      adjacent bone were evaluated. A diffuse T2-hyperintense signal of multiple muscle
      groups was seen in all patients (bilateral in 12) involving quadriceps (n=13,
      93%), adductors (n=13, 93%) and iliopsoas (n=12, 86%) with contrast enhancement
      in n=11 (79%), n=8 (57%) and n=8 (57%) patients. All patients had nonenhancing
      areas (mean size 2 x 3.5 x 5.8 cm) within diffusely enhancing muscles. HO
      formation occurred around these nonenhancing areas in four patients with computed
      tomography follow-up. Other MR findings included fascial edema (n=14, 100%),
      fascial enhancement (n=13, 93%), subcutaneous edema (n=13, 93%), subcutaneous
      enhancement (n=12, 86%), bone marrow edema (n=5, 36%), and joint effusion (n=12,
      86%). MRI reveals mostly bilateral edema and enhancement of muscles, fascia and
      subcutaneous tissue during acute onset of HO. HO develops in the periphery of
      well-defined areas of no enhancement.

PMID- 15856245
TI  - Age-related signal intensity changes in the corpus callosum: assessment with
      three orthogonal FLAIR images.
AB  - The presence of age-related hyperintensities of the corpus callosum has not been
      thoroughly evaluated. Fifty-two patients of 50 years of age or older (mean, 71
      years; range, 50-87 years) were included in this study. Fluid-attenuated
      inversion recovery images were obtained in three orthogonal planes.
      Periventricular hyperintensities (PVHs) and deep white matter hyperintensities
      (DWMHs) were graded according to Fazekas' rating scale. Correlations between the
      presence of hyperintensities in the corpus callosum and age, and the grade of PVH
      and DWMH were statistically analyzed. PVH was categorized as grade 0 (n=4), grade
      1 (n=28), grade 2 (n=10), or grade 3 (n=10). DWMH was categorized as grade 0
      (n=4), grade 1 (n=25), grade 2 (n=8), or grade 3 (n=15). Hyperintensity was
      considered present in the corpus callosum in 31 of the 52 patients (60%). In
      these 31 patients, PVH was categorized as grade 1 (n=16), grade 2 (n=7), or grade
      3 (n=8), while DWMH was categorized as grade 0 (n=1), grade 1 (n=10), grade 2
      (n=7), or grade 3 (n=13). The presence of callosal hyperintensities was
      significantly correlated with age (p=0.001), and with PVH (p=0.04) and DWMH
      grades (p=0.004). Hyperintensities may be present in the corpus callosum with
      aging, and are correlated with PVH and DWMH.

PMID- 15856246
TI  - Quantitative cartilage volume measurement using MRI: comparison of different
      evaluation techniques.
AB  - This study was aimed to investigate the accuracy and time saving of MRI Argus
      application in the assessment of cartilage volume in osteoarthritic knees. Twelve
      knees of patients suffering from osteoarthritis were scanned with a 1.5 T MRI
      using a 3D gradient echo sequence with selective water excitation. Cartilage
      volume of the tibial and patellar compartment was determined with a validated
      multiprocessing computer system (Octane Duo, Silicon Graphics, Mountain View,
      Calif., USA). The calculated cartilage volumes were compared to the results
      acquired by the Argus (Siemens Inc., Erlangen, Germany) application software
      using the MRI data sets. Compared to the multiprocessing computer system a time
      saving of at least 30 min for cartilage volume determination was achieved. The
      mean differences of Argus versus the multiprocessing computer system were 4.26+/
      0.84 and 7.80+/-0.87% for the medial and lateral tibial plateau and 5.94+/-0.59%
      for the patella (no statistical significant difference; P>0.05). The applied
      Argus software can be used for fast and accurate determination of cartilage
      volume in the knee joint.

PMID- 15856247
TI  - Comparison of volume, four- and eight-channel head coils using standard and
      parallel imaging.
AB  - Array coils can potentially offer increased signal-to-noise ratio (SNR) over
      standard coils adjacent to the array elements, while preserving the SNR at the
      center of the volume. The SNR advantage should theoretically increase with the
      number of array elements. Parallel acquisition techniques (PAT), on the other
      hand, can benefit acquisition times or spatial resolution at a cost to SNR as
      well as image quality. This study examines the question of whether SNR and image
      quality are still acceptable with two different array coils (four and eight
      channels) in conjunction with PAT when compared to standard imaging with a volume
      coil. All imaging was on a 1.5 T MR scanner. T2-weighted, FLAIR, diffusion
      weighted, and time of flight (TOF) angiography images were performed with and
      without PAT in a phantom and in ten healthy volunteers. The phantom measurements
      demonstrated superior SNR for the eight-channel coil versus the four-channel and
      standard head coils. Using the eight-channel head coil for in vivo imaging, image
      quality with PAT (acceleration factor=2) was scored similar to images without PAT
      using the volume coil. The four-channel head coil suffered from inhomogeneity,
      lower SNR and poorer image quality when using PAT compared to standard imaging
      with the volume head coil. Both the in vivo and the phantom results indicate that
      the eight-channel head coil should be used for the highest quality brain images;
      this coil can be combined with PAT sequences for shorter acquisition time without
      a significant decrease in image quality relative to a volume coil without PAT.

PMID- 15856248
TI  - Disseminated dendriform pulmonary ossification associated with usual interstitial
      pneumonia: incidence and thin-section CT-pathologic correlation.
AB  - The aim of this work was to assess the incidence of disseminated pulmonary
      dendriform ossification in usual interstitial pneumonia and nonspecific
      interstitial pneumonia, and to correlate thin-section computed tomography (CT)
      and histopathologic findings. We retrospectively reviewed thin-section CT and
      pathologic specimens of biopsy-proven usual interstitial pneumonia (75 patients,
      57 men and 18 women, mean age 60 years, range 29-83 years) and nonspecific
      interstitial pneumonia (44 patients, 9 men and 35 women, mean age 55 years, range
      20-73 years). On review of CT and histopathologic specimens, diffuse dendriform
      ossification was identified in five (four men and one woman, age range 41-68
      years, mean 58 years) of 75 patients (6.7%) with usual interstitial pneumonia. It
      was not seen in any of 44 patients with nonspecific interstitial pneumonia. With
      thin-section CT (osteoporosis window; window width 818, level 273), disseminated
      dendriform pulmonary ossification was detected as multiple tiny calcifications in
      bibasilar subpleural lungs (100% sensitive and 100% specific when compared with
      histopathologic findings as the gold standard). The thin-section CT finding of
      multiple tiny calcifications in bibasilar subpleural lungs might be of some help
      in the differential diagnosis between usual interstitial pneumonia and
      nonspecific interstitial pneumonia, considering they were not seen in any
      patients with nonspecific interstitial pneumonia (0%, 0/44) in our series.

PMID- 15856249
TI  - 1H chemical shift imaging of the brain in guanidino methyltransferase deficiency,
      a creatine deficiency syndrome; guanidinoacetate accumulation in the gray matter.
AB  - MR spectroscopy results in a mild case of guanidinoacetate methyltransferase
      (GAMT) deficiency are presented. The approach differs from previous MRS studies
      in the acquisition of a chemical shift imaging spectral map showing gray and
      white matter with the corresponding spectra in one overview. MR spectroscopy
      revealed guanidinoacetate (GAA) in the absence of creatine. New is that GAA
      signals are more prominent in gray matter than in white. In the prevailing view,
      that enzyme deficiency is localized in liver and pancreas and that all GAA is
      transported into the brain from the blood and the cerebrospinal fluid, this would
      be compatible with a more limited uptake and/or better clearance of GAA from the
      white matter compared to the grey matter.

PMID- 15856250
TI  - MRI in guiding and assessing intramyocardial therapy.
AB  - Cardiovascular intervention, using MRI guidance, is challenging for clinical
      applications. Real-time imaging sequences with high spatial resolution are needed
      for monitoring intramyocardial delivery of drug, gene, or stem cell therapies.
      New generation MR scanners make local intramyocardial and vascular wall therapies
      feasible. Contrast-enhanced MRI is used for assessing myocardial ischemia,
      infarction, and scar tissue. Active (microcoils) and passive (T1 and T2*
      mechanisms) tracking methods have been used for visualization of endovascular
      catheters. Safety issues related to potential heating of endovascular devices is
      still a major obstacle for MRI-guided interventions. Fabrication of MRI
      compatible interventional devices is limited. Noninvasive imaging strategies will
      be critical in defining spatial and temporal characteristics of angiogenesis and
      myocardial repair as well as in assessing the efficacy of new therapies in
      ischemic heart disease. MRI contrast media improve the capability of MRI by
      delineating the target and vascular tree. Labeling stem cells enables MRI to
      trace distribution, differentiation, and survival in myocardium and vascular
      wall. In the long term, MRI in guiding and assessing intramyocardial therapy may
      circumvent the limitations of peripherally administered cell therapy, X-ray
      angiography, and nuclear imaging. MRI represents a highly attractive discipline
      whose systematic development will foster the implementation of new cardiac and
      vascular therapies.

PMID- 15856251
TI  - Displaced aortic arch sign on chest radiographs: a new sign for the detection of
      a left paratracheal esophageal mass.
AB  - Our objective was to ascertain whether displacement of the aortic knob on chest
      radiographs could be used as a sign to detect a left paratracheal esophageal
      mass. Sixty-one consecutive pathologically proven esophageal cancer patients were
      included in this study according to the following criteria: tumor at the aortic
      arch level; chest radiographs in the neutral position; no unilateral volume loss
      in the lung. Sixty-one sex- and age-matched subjects served as the control group.
      To measure the extent of displacement of the aortic arch, we drew a circle over
      the aortic knob, fitting more than one-quarter of the circumference on the chest
      radiograph. The distance between the medial end of the circle and the left margin
      of the trachea (aortic displacement value, ADV) was measured. The difference of
      the ADV between the study group and the control group was analyzed using a paired
      t test. The aortic displacement value was significantly larger in the study group
      (11.7+/-4.5 mm) than in the control group (5.6+/-2.9 mm). When we applied 10 mm
      as a threshold level, sensitivity and specificity on detection of esophageal
      cancer were 78.7 and 78.7%, respectively. Displacement of the aortic knob may be
      a useful sign to indicate a left paratracheal esophageal mass.

PMID- 15856252
TI  - Whole-body MRI at high field: technical limits and clinical potential.
AB  - This review seeks to clarify the most important implications of higher magnetic
      field strength for clinical examinations of the whole body. An overview is
      provided on the resulting advantages and disadvantages for anatomical, functional
      and biochemical magnetic resonance examinations in different regions of the body.
      It is demonstrated that susceptibility-dependent imaging, chemical shift
      selective (e.g., fat-suppressed) imaging, and spectroscopic techniques clearly
      gain from higher field strength. Problems due to shorter wavelength and higher
      radio frequency energy deposition at higher field strength are reported,
      especially in examinations of the body trunk. Thorax examinations provided
      sufficient homogeneity of the radio frequency field for common examination
      techniques in most cases, whereas abdominal and pelvic imaging was often hampered
      by undesired dielectric effects. Currently available and potential future
      strategies to overcome related limitations are discussed. Whole-body MRI at
      higher field strength currently leads to clearly improved image quality using a
      variety of established sequence types and for examination of many body regions.
      But some major problems at higher field strength have to be solved before high
      field magnetic resonance systems can really replace the well-established and
      technically developed magnetic resonance systems operating at 1.5 T for each
      clinical application.

PMID- 15856253
TI  - Applications and literature review of the BI-RADS classification.
AB  - The Breast Imaging Reporting and Data System (BI-RADS) of the American College of
      Radiology (ACR) is a tool created to reduce variability in the terminology used
      in mammographic reports. An illustration of mammographic examples from our
      institution interpreted according to the BI-RADS lexicon of the American College
      of Radiology (ACR) is presented. A literature review concerning the usefulness
      and limitations of the BI-RADS lexicon is given.

PMID- 15856254
TI  - Role of ultrasound in the preoperative staging of patients with breast cancer.
AB  - The aim of this study was to evaluate the ability of axillary ultrasound (US) and
      US-guided fine-needle aspiration biopsy (FNAB) to detect axillary LN metastases.
      Between January 2001 and September 2003, axillary US was performed in 165
      patients with cytologically or histologically proven breast cancer and clinically
      non-palpable axillary LNs. In patients with US suspicious LNs, US-guided FNAB was
      performed and patients with cytologically proven malignant LNs proceeded directly
      to the ALND. In 49/90 patients with US suspicious LNs, US-guided FNAB was
      performed. It was positive in 33/49 patients. Definitive histology report
      revealed LN metastases in 65/165 patients. The sensitivity, specificity, positive
      and negative predictive value of the US-FNAB, were 84, 91, 97 and 62%. Axillary
      US in a combination with US-FNAB is a valuable method in preoperative staging of
      patients with breast cancer. Almost 50% of patients with LN metastases can be
      spared the second operation. However, it is very much operator-dependent and
      equipment-dependent.

PMID- 15856255
TI  - [Acute vision loss after intraocular foreign body injury 20 years ago].

PMID- 15856256
TI  - Modification of statocyst input to local interneurons by behavioral condition in
      the crayfish brain.
AB  - Posture control by statocysts is affected by leg condition in decapod
      crustaceans. We investigated how, in the crayfish brain, the synaptic response of
      local interneurons to statocyst stimulation was affected by leg movements on and
      off a substratum. The magnetic field stimulation method permitted sustained
      stimulation of statocyst receptors by mimicking body rolling. The statocyst
      driven local interneurons were classified into four morphological groups (Type-I
      IV). All interneurons except Type-IV projected their dendritic branches to the
      parolfactory lobe of the deutocerebrum where statocyst afferents project
      directly. Type-I interneurons having somata in the ventral-paired lateral cluster
      responded invariably to statocyst stimulation regardless of the leg condition,
      whereas others having somata in the ventral-unpaired posterior cluster showed
      response enhancement or suppression, depending on the cell, during leg movements
      on a substratum, but no response change during free leg movements off the
      substratum. The synaptic responses of Type-II and IV interneurons were also
      affected differently by leg movements depending on the substratum condition,
      whereas those of Type-III remained unaffected. These findings suggest that the
      statocyst pathway in the crayfish brain is organized in parallel with local
      circuits that are affected by leg condition and those not affected.

PMID- 15856257
TI  - Interactions of mechanical stimuli and sex pheromone information in antennal lobe
      neurons of a male moth, Spodoptera littoralis.
AB  - Male moths respond to sex pheromone sources with up-wind flight behaviour.
      Localization of the odour source requires not only detection of the olfactory
      stimulus, but also other sensory input regarding, e.g. visual and mechanical
      stimuli. Thus, integration of different types of sensory input is necessary. It
      is, however, not known where in the central nervous system the integration of
      information regarding different sensory modalities takes place. Using
      intracellular recording and staining techniques, we investigated neurons in the
      antennal lobe of Spodoptera littoralis, during stimulation with a mechanical
      stimulus and a sex pheromone. Fifteen percent of all the neurons investigated
      responded to the mechanical stimulus and the majority of these neurons showed
      altered responses if the olfactory stimulus was added. A receptor neuron
      responding only to the wind stimulus was found to arborise in the antennal lobe.
      Most projection neurons responded with an enhanced action potential frequency to
      the combined stimulus. In local interneurons, enhancement, depression, or no
      change of the responses to the wind stimulus was found when the olfactory
      stimulus was added. The results suggest that neurons present in the antennal lobe
      integrate mechanosensory and olfactory input, possibly assisting the moths to
      orient during up-wind flight towards an odour source.

PMID- 15856258
TI  - Growing skull fracture: a posttraumatic neosuture.
AB  - CONTEXT: A case of a growing skull fracture presenting in adulthood is reported.
      Pertinent literature was reviewed with an emphasis on pathogenesis. EVIDENCE
      ACQUISITION: A search through MEDLINE from 1994 through 2004 was used and
      supplemented by searches of secondary sources retrieved from referenced articles.
      EVIDENCE SYNTHESIS: Current hypotheses for the pathogenesis of growing skull
      fractures were critically analyzed. A new hypothesis based in more recent data is
      proposed in an attempt to better understand this process. CONCLUSIONS: The
      proposed hypothesis seems to explain better the timing in which the clinical
      features in growing skull fracture develop.

PMID- 15856259
TI  - Developmental plasticity after right hemispherectomy in an epileptic adolescent
      with early brain injury.
AB  - OBJECTIVES: The authors present the case of an adolescent affected with
      refractory epilepsy due to a neonatal ischemic infarction of the right medial
      cerebral artery. Hemiplegic since the first months of life, she began presenting
      motor partial seizures associated with drop attacks at 4.5 years; these were
      initially well controlled by antiepileptic drugs, but at 10 years seizures
      appeared again and became refractory. Thus, at 14 years and 10 months, she was
      submitted to a right hemispherectomy that made her rapidly seizure free. In the
      post-surgical follow-up lasting 5 years, neuropsychological serial assessments
      showed an impressive progressive improvement of cognitive skills, namely,
      visuospatial abilities. This case seems to challenge the widely spread feeling
      that functional catch-up in brain-injured children could only occur early in
      life. In effect, the astonishing recovery especially of visuospatial skills in
      our case occurred in adolescence after a late surgical intervention of right
      hemispherectomy. METHODS: Different neuropsychological aspects are discussed. The
      reorganisation process recovered the spatial and linguistic abilities as well as
      the verbal and visuospatial memory; however, there was a persistent impairment of
      complex spatial and perceptual skills as well as recall abilities. Despite the
      deficit of complex visual stimuli processing, the patient showed a good
      performance in the recognition of unknown faces. CONCLUSIONS: Probably, the
      absence of seizures in the first 4 years of life could have allowed a generally
      adequate compensatory reorganisation, successively masked by the persistent and
      diffuse epileptic disorder. The seizure control produced by surgery eventually
      made evident the effectiveness of the brain reorganisation.

PMID- 15856261
TI  - Spontaneous gallbladder perforation in a neonate.
AB  - We describe the case of a 700-g neonate who presented with abdominal
      discolouration, distension, and rapid clinical deterioration. At laparotomy, a
      perforation in the neck of the gallbladder was found, which was simply over-seen.
      Perforation of the gallbladder should be considered in the differential diagnosis
      in such neonates. The surgical management should be direct repair, without
      resorting to a cholecystectomy.

PMID- 15856262
TI  - Congenital absence of the pericardium associated with congenital diaphragmatic
      hernia and hepatic hemangioendothelioma: case report and review of the
      literature.
AB  - An unusual case of a neonate with absent pericardium, left-sided diaphragmatic
      hernia, and hepatic hemangioendothelioma is described. The posterolateral
      diaphragmatic hernia was successfully repaired, and agenesis of the pericardium
      did not interfere with cardiac function postoperatively. The hepatic tumour was a
      coincidental radiological finding, while liver function and the biochemical
      profile were normal. We also present a review of the literature on congenital
      absence of the pericardium and conclude that all cases should be screened for
      cardiac and hepatic anomalies.

PMID- 15856263
TI  - Tumour regression grading in the evaluation of tumour response after different
      preoperative radiotherapy treatments for rectal carcinoma.
AB  - BACKGROUND AND AIMS: Preoperative radiotherapy (PRT) for rectal carcinoma has
      been shown to cause tumour regression and increase local control and patient
      survival. The aim of this study was to examine the usefulness of tumour
      regression grading (TRG) in quantifying the effect of PRT. METHODS: Depending on
      the tumour stage (uT), as defined by preoperative endorectal ultrasound (ERUS),
      fixity and distance from the anal verge, 126 patients with rectal cancer
      underwent either surgery alone, or received short-course 25-Gy radiotherapy or
      long-course 50-Gy radiotherapy combined with 5-fluorouracil (5-FU) before
      surgery. TRG in each group was assessed and compared with the downstaging,
      defined as a change in preoperative uT stage and pathologic stage (pT). RESULTS:
      Complete response (no residual tumour, TRG 1) was seen in 7% of the patients
      (3/44) and total or major regression (TRG 1-3) in 73% of the patients (32/44)
      treated with 50-Gy chemoradiation. Of those treated with 25-Gy PRT, 21% (9/42)
      showed major tumour regression. Of the patients who underwent ERUS and PRT, 32%
      (26/83) were downstaged when comparing uT with pT, but 53% (14/26) of the
      downstaged tumours showed no response by TRG. In comparison, 50% (28/57) of the
      tumours with no downstaging showed a marked response by TRG (p=0.05).
      CONCLUSIONS: Tumour regression grading offers detailed information of the effect
      of PRT and shows that tumour regression is more marked after long-term
      chemoradiation than after short-course radiotherapy (p=0.02). In contrast, T
      stage downstaging was similar in both groups and did not correlate with the TRG
      results (p=0.05).

PMID- 15856264
TI  - Behcet's disease: a rare cause of lower gastrointestinal bleeding.

PMID- 15856266
TI  - NF1 tumor suppressor in epidermal wound healing with special focus on wound
      healing in patients with type 1 neurofibromatosis.
AB  - Type 1 neurofibromatosis syndrome (NF1) has been linked with mutations of the NF1
      gene which encodes tumor suppressor neurofibromin, a regulator of Ras-MAPK
      signaling. In human epidermis, keratinocytes express NF1 tumor suppressor and it
      may have a distinctive function in these cells during wound healing, such as
      regulating Ras activity. NF1 expression was first studied during the epidermal
      wound healing using suction blister method. NF1 gene expression increased both in
      hypertrophic and migrating zones of the healing epidermis, and also in dermal
      fibroblasts underneath the injury. This prompted us to study epidermal wound
      healing in NF1 patients. Wound healing efficiency was evaluated 4 days after
      blister induction by clinical, physiological and histological methods. Epidermal
      wound healing was equally effective in NF1 patients and healthy controls. In
      addition, dermal wound healing appears to function normally in NF1 patients based
      on retrospective and follow-up study of biopsy scars. Furthermore, the healing
      wounds were analyzed immunohistochemically for cell proliferation rate and Ras
      MAPK activity. Neither epidermal keratinocytes nor dermal fibroblasts showed
      difference in the cell proliferation rate or Ras-MAPK activity between NF1
      patients and controls. Interestingly, NF1 patients displayed increased cell
      proliferation rate and Ras-MAPK activity in periarteriolar tissue underneath the
      wound. The results of the study suggest that epidermal wound healing is not
      markedly altered in NF1 patients. Furthermore, NF1 protein seems not to have an
      important function as a Ras-MAPK regulator in epidermal keratinocytes or dermal
      fibroblasts but instead appears to be regulator of Ras-MAPK signaling in vascular
      tissues.

PMID- 15856265
TI  - Blocking MAdCAM-1 in vivo reduces leukocyte extravasation and reverses chronic
      inflammation in experimental colitis.
AB  - BACKGROUND: Leukocyte recruitment to sites of intestinal inflammation is a
      crucial multi-step process, leading ultimately to the accumulation of cells in
      the inflamed tissue. These interactions in the gut are critically dependent on
      the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is expressed on
      endothelial cells within the mesenteric lymph nodes and the lamina propria of the
      intestine. Here, we investigate the pathophysiologic role of MAdCAM-1 in the
      intestinal microcirculation in vivo. METHODS: Using a standard mouse model,
      chronic colitis was established after four cycles of dextran sodium sulfate (DSS)
      application. MAdCAM-1 expression was investigated by immunohistochemistry and
      Western blotting, as well as real-time polymerase chain reaction (PCR).
      Intravital microscopy was used to study the role of MAdCAM-1 on leukocyte
      endothelium interactions and leukocyte extravasation. RESULTS: Significant
      changes in MAdCAM-1 were observed in mice with chronic DSS-induced colitis.
      Upregulation of MAdCAM-1 expression in chronic colitis was demonstrated on a
      protein and messenger ribonucleic acid (mRNA) level. Anti-MAdCAM-1 treatment lead
      to a marked reduction (>60%) of leukocyte sticking and extravasation in vivo,
      compared to the controls. This was parallelled by a significant reduction (45%)
      of intestinal inflammation, as measured by the histologic grading score.
      CONCLUSION: These in vivo results demonstrate a distinct role of MAdCAM-1 in
      inflammatory intestinal diseases, and suggest that therapeutic strategies
      targeting this adhesion molecule could be useful in the treatment of chronic
      colitis.

PMID- 15856267
TI  - Incidental detection of S. pyogenes-DNA in psoriatic skin by PCR.
AB  - Psoriasis vulgaris is a T cell-mediated autoimmune skin disease. First disease
      onset and disease worsening are often triggered by tonsillar infection with
      Streptococcus pyogenes. Here we demonstrate the incidental detection of S.
      pyogenes DNA in samples of different biological origin from patients with chronic
      plaque-type psoriasis by PCR. These findings may support the model of molecular
      mimicry in psoriasis pathogenesis.

PMID- 15856268
TI  - Posthysterectomy intestinal prolapse after coitus and vaginal repair.
AB  - INTRODUCTION: Transvaginal bowel evisceration following either vaginal or
      abdominal gynecologic operations is a very rare complication. Furthermore,
      vaginal cuff rupture with the prolapse of the small bowel through the vagina
      during sexual intercourse after abdominal hysterectomy in a premenopausal woman
      is even more rare. However, regardless of the etiology, transvaginal evisceration
      requires prompt recognition and surgical intervention. CASE REPORT: Here, we
      report a premenopausal woman who developed transvaginal bowel evisceration during
      the first postoperative intercourse.

PMID- 15856269
TI  - The changing motives of cesarean section: from the ancient world to the twenty
      first century.
AB  - BACKGROUND: Cesarean delivery has been practiced for ages, although originally as
      a universally postmortem procedure. It is referred to in the myths and folklore
      of many ancient societies, for some of the infants delivered in this way
      survived, even though their mothers did not. Since the Renaissance, the objective
      of the procedure has gradually shifted towards saving the lives of both the
      mother and the child, and this has become ever more possible, as maternal and
      perinatal mortality and morbidity decreased dramatically during the twentieth
      century. CURRENT ISSUES: Today (at the beginning of twenty-first century), we are
      not only concerned with the safety and health of the mother and the child, but
      also with mother's desires and preferences and the child's rights.

PMID- 15856270
TI  - Y-chromosomal STR haplotypes and their applications to forensic and population
      studies in east Asia.
AB  - We have analyzed 11 Y-STR loci (DYS19, the two DYS385 loci, DYS388, DYS389I/II,
      DYS390, DYS391, DYS392, DYS393, DXYS156Y) in 700 males from ten ethnic groups in
      east Asia in order to evaluate their usefulness for forensic and population
      genetic studies. A total of 644 different haplotypes were identified, among which
      603 (86.14%) were individual-specific. The haplotype diversity averaged over all
      populations was 0.9997; using only the nine Y-STRs comprising the "minimal
      haplotype" (excluding DYS388 and DXYS156Y) it was 0.9996, a value similar to that
      found in 1924 samples from other Asian populations (0.9996; Lessig et al. Legal
      Medicine 5(2003) 160-163), and slightly higher than in European populations
      (0.9976; n=11,610; Roewer et al. For Sci International (2001) 118:103-111). All
      of the individual east Asian populations examined here had high haplotype
      diversity (> or =0.997), except for the Mongolians (0.992) and Manchurians
      (0.960). The most frequent haplotype identified by the nine markers was present
      at only 1% (7/700). Population comparisons based on Phi(ST) or rho genetic
      distance measures revealed clustering according to the traditional northeast
      southeast distinction, but with exceptions. For example, the Yunnan population
      from southern China lay among the northern populations, possibly reflecting
      recent migration, while the Korean population, traditionally considered northern,
      lay at the boundary between northern and southern populations. An admixture
      estimate suggested 55(51-59)% northern, 45(41-49)% southern contribution to the
      Koreans, illustrating the complexity of the genetic history of this region.

PMID- 15856271
TI  - Comments on Hausmann et al.: neuronal apoptosis following human brain injury.

PMID- 15856272
TI  - In vivo confocal microscopic evaluation of Langerhans cell density and
      distribution in the normal human corneal epithelium.
AB  - PURPOSE: To examine the density and distribution of Langerhans cells (LCs) in the
      corneal epithelium of healthy volunteers. METHODS: Two hundred eyes of 112
      healthy volunteers (age 21-81 years) without history of ocular inflammation or
      surgery were examined in vivo with the combination of the Heidelberg Retina
      Tomograph II and the Rostock Cornea Module. For statistical analysis data of one
      eye per volunteer were used, with random selection of one eye in those volunteers
      in whom both eyes were studied. RESULTS: As studied by in vivo confocal
      microscopy, 31.3% of all volunteers presented with LCs (24 volunteers with both
      eyes studied and 11 volunteers with only one eye studied). In 30 of these 35
      volunteers, LCs were found in both the central and peripheral corneal epithelium.
      More than 50% of male volunteers with LCs were younger than 30 years; in
      contrast, almost two thirds of females with LCs were above 50 years in age. The
      density of LCs in the periphery of the cornea (98+/-8 cells/mm2; range 0-208
      cells/mm2) was significantly (p<0.001) greater than in the central part (34+/-3
      cells/mm2; range 0-64 cells/mm2). LCs were located at depths of 35-60 microm,
      with different frequency. While LCs were sparse at the level of deep intermedial
      cells (5.7% of the volunteers), 11.4% of the volunteers presented with LCs within
      the level of basal epithelial cells and most of the eyes (82.9%) had LCs at the
      level of basal epithelial cells and subbasal nerve plexus. Moreover, LCs
      presented as either large cells bearing long processes or smaller cells lacking
      cell dendrites, presumably indicating mature and immature phenotype,
      respectively. CONCLUSION: The Heidelberg Retina Tomograph II in combination with
      the Rostock Cornea Module enables in vivo assessment of density and distribution
      of LCs in the corneal epithelium, providing insight into human eye immunology.
      These data may now provide a suitable basis for further investigations in ocular
      pathology.

PMID- 15856273
TI  - Characterization of renal interstitial fibroblast-specific protein 1/S100A4
      positive cells in healthy and inflamed rodent kidneys.
AB  - Fibrosis is considered as a central factor in the loss of renal function in
      chronic kidney diseases. The origin of fibroblasts and myofibroblasts that
      accumulate in the interstitium of the diseased kidney is still a matter of
      debate. It has been shown that accumulation of myofibroblasts in inflamed and
      fibrotic kidneys is associated with upregulation of fibroblast-specific protein 1
      (FSP1, S100A4), not only in the renal interstitium but also in the injured renal
      epithelia. The tubular expression of FSP1 has been taken as evidence of
      myofibroblast formation by epithelial-mesenchymal transition (EMT). The identity
      of FSP1/S100A4 cells has not been defined in detail. We originally intended to
      use FSP1/S100A4 as a marker of putative EMT in a model of distal tubular injury.
      However, since the immunoreactivity of FSP1 did not seem to fit with the
      distribution and shape of fibroblasts or myofibroblasts, we undertook the
      characterization of FSP1/S100A4-expressing cells in the interstitium of rodent
      kidneys. We performed immunolabeling for FSP1/S100A4 on thin cryostat sections of
      perfusion-fixed rat and mouse kidneys with peritubular inflammation, induced by
      thiazides and glomerulonephritis, respectively, in combination with ecto-5'
      nucleotidase (5'NT), recognizing local cortical peritubular fibroblasts, with
      CD45, MHC class II, CD3, CD4 and Thy 1, recognizing mononuclear cells, with alpha
      smooth muscle actin (alphaSMA), as marker for myofibroblasts, and vimentin for
      intracellular intermediate filaments in cells of mesenchymal origin. In the
      healthy interstitium of rodents the rare FSP1/S100A4+ cells consistently co
      expressed CD45 or lymphocyte surface molecules. Around the injured distal tubules
      of rats treated for 3-4 days with thiazides, FSP1+/S100A4+, 5'NT+, alphaSMA+,
      CD45+ and MHC class II+ cells accumulated. FSP1+/S100A4+ cells consistently co
      expressed CD45. In the inflamed regions, alphaSMA was co-expressed by 5'NT+
      cells. In glomerulonephritic mice, FSP1+/S100A4+ cells co-expressed Thy 1, CD4 or
      CD3. Thus, in the inflamed interstitium around distal tubules of rats and of
      glomerulonephritic mice, the majority of FSP1+ cells express markers of
      mononuclear cells. Consequently, the usefulness of FSP1/S100A4 as a tool for
      detection of (myo)fibroblasts in inflamed kidneys and of EMT in vivo is put into
      question. In the given rat model the consistent co-expression of alphaSMA and
      5'NT suggests that myofibroblasts originate from resident peritubular
      fibroblasts.

PMID- 15856274
TI  - Selective binding of biotinylated albumin to the lymphoid microvasculature.
AB  - Chemically modified albumin binds to the surface of microvascular endothelia
      lining the vessel wall in several tissues. In this paper, we report that
      following their biotinylation, ovalbumin (bioOVA) and bovine serum albumin (BSA)
      [biotinyated albumin (bioAlb)] showed heterogeneous binding to distinct vascular
      subsets in different lymphoid tissues. The binding of bioAlb could be
      demonstrated both by fluorescent and enzymohistochemical techniques. In the
      spleen, the reaction was restricted to the red pulp sinuses whereas the white
      pulp vessels (including the central arteriole) and the marginal sinus were
      negative for bioAlb binding. In lymph nodes, the strongest labeling was observed
      in the medullary sinuses. In the thymus, the most prominent labeling of
      capillaries was restricted to the corticomedullary area where it was found to be
      less intense compared with the splenic reaction. The splenic reactivity of bioAlb
      in the mouse was defined using antibodies against endothelial cell subsets in
      distinct vascular beds in the red pulp and marginal zone, respectively. The
      bioAlb-binding elements of the splenic red pulp sinus architecture corresponded
      to the display of hyaluronan receptor stabilin-2 and subset-specific marker IBL
      9/2 while they differed from the expression pattern of both the complementary red
      pulp sinus subset and the marginal sinus-lining cells expressing MAdCAM-1
      antigen, respectively. Similar red pulp sinus-restricted reactivity could be
      demonstrated in the human, rat, and guinea pig. The use of bioAlb may thus offer
      a reliable probe for the histological identification of select microvascular
      endothelia in lymphoid tissues.

PMID- 15856275
TI  - Localization of TRPC1 channel in the sinus endothelial cells of rat spleen.
AB  - The ultrastructural localization of transient receptor potential C1 (TRPC1)
      channels in the sinus endothelial cells of rat spleen was examined by confocal
      laser scanning and electron microscopy. In addition, the localization of the
      closely associated proteins and channels, VE-cadherin, calreticulin, inositol
      1,4,5-trisphosphate receptors type 1 (IP3R1), and ryanodine receptor (RyR), was
      also examined. Immunofluorescence microscopy of tissue cryosections revealed
      TRPC1 channels to be localized within the cytoplasm, in the superficial layer of
      the apical and basal parts of the cells, and in the junctional area of the
      adjacent endothelial cells. The distribution of Ca2+-storing tubulovesicular
      structures within endothelial cells was established by using tissue sections
      treated with osmium ferricyanide. Electron microscopy revealed densely stained
      tubulovesicular structures closely apposed to the plasma membrane and that
      occasionally ran closely parallel to the plasma membrane and near the caveolae
      and junctional apparatus. Immunolocalization analysis at the electron microscopy
      level using immunogold bound to the secondary antibody confirmed that TRPC1
      channels were localized in the plasma membrane, caveolae, and vesicular
      structures in the subplasmalemmal cytoplasm of sinus endothelial cells.
      Calreticulin was predominantly localized in endoplasmic reticulum. IP3R1 and RyR,
      considered to be type 3, were colocalized in endoplasmic reticulum in proximity
      to the plasma membrane and caveolae. Thus, TRPC1 channels in sinus endothelial
      cells of the spleen might play an important role in controlling blood cell
      passage through phenomena including cytoskeletal reorganization, cell retraction,
      and disassembly of adherens junctions.

PMID- 15856276
TI  - Distribution of caveolin-1 and connexin43 in normal and injured alveolar
      epithelial R3/1 cells.
AB  - Using the new alveolar epithelial type I-like cell line R3/1 derived from fetal
      rat lung, we studied the distribution of connexin43 and caveolin-1 under
      conditions of bleomycin-induced injury in vitro. We show that under normal as
      well as under conditions of injury, endogenous connexin43 does not directly
      interact with endogenous caveolin-1 as revealed by immunofluorescence,
      glutathione S-transferase/caveolin-1 "pull down" assay, and co
      immunoprecipitation experiments. The assessment of Triton X-100 solubility
      revealed that caveolin-1 was abundant in detergent-resistant membrane fractions.
      This is consistent with the localization of caveolin-1 in the lipid
      rafts/caveolae. Similarly, phosphorylated connexin43 was preferably detected in
      the Triton-insoluble fraction. Using a sucrose gradient we demonstrated that the
      majority of phosphorylated connexin43 colocalizes with caveolin-1 in lipid rafts,
      whereas all other forms of connexin43 remain in the bulk of cellular membranes
      and cytosolic proteins. Triton solubility assessment of bleomycin-treated cells
      revealed no differences in the caveolin-1 and connexin43 distribution. A further
      interesting outcome of our study is the shift of caveolin-1 from the lipid
      raft/caveolae fractions to the non-caveolar fractions after bleomycin treatment
      indicating an intracellular retention of caveolin-1. This result suggests the
      possibility that the translocation of caveolin-1 could be an important event
      regulating the metabolism of alveolar epithelial lung cells after injury.

PMID- 15856277
TI  - Vascular endothelial growth factor plays an important autocrine/paracrine role in
      the progression of osteoarthritis.
AB  - Vascular endothelial growth factor (VEGF) plays an essential role in the
      angiogenesis of growing cartilage. Although VEGF expression in cartilage vanishes
      in normal adults, VEGF is known to be expressed in chondrocytes of osteoarthritic
      (OA) cartilage. As little information is available on the VEGF expression in the
      cartilage of OA-like lesions of the temporomandibular joint (TMJ), VEGF
      expression in the condylar cartilage of TMJs of rats affected with OA was
      examined. To evoke OA, mechanical stress was applied by forced jaw opening for 10
      or 20 days. After 20 days, marked OA-like lesions were observed in the condyle.
      VEGF was expressed in the chondrocytes of the mature and hypertrophic cell layers
      of the intermediate and posterior region of the condyle. The percentage of VEGF
      immunopositive chondrocytes significantly increased with the period of applied
      mechanical stress. Furthermore, tartrate-resistant acid phosphatase (TRAP)
      staining of the condylar cartilage showed significant increment of osteoclasts in
      the mineralized layer subjacent to the hypertrophic layer where high VEGF
      expression could be detected. The results suggest that VEGF plays an important
      role in the progression of OA.

PMID- 15856278
TI  - Non-aqueous permanent mounting for immunofluorescence microscopy.
AB  - It is generally assumed that an aqueous mounting medium is necessary for the
      preservation of immunofluorescent-labelled microscopical preparations and
      polyvinyl alcohol-based solutions (e.g. Mowiol) being the most frequently used
      mounting media; however, both the quality and intensity of the fluorescence
      signal in most immunolabelled preparations after aqueous mounting slowly diminish
      with time, and finally, samples become unsuitable for examination. In the present
      work, we describe a very simple and rapid non-aqueous mounting procedure for
      cultured cells and tissue sections, which preserves the fluorescent signal in an
      excellent way after immunodetection or use of other specific labelling methods.
      It is based on the current histological protocol in which, after fluorescence
      labelling, preparations are dehydrated in ethanol, cleared in xylene and mounted
      in DePeX. Using this non-aqueous mounting medium, the fluorescent signal remains
      high and stable, allowing a suitable and permanent preservation of labelled and
      counterstained microscopical preparations.

PMID- 15856279
TI  - Immunocytochemical characterization of two types of microvillar cells in rodent
      olfactory epithelium.
AB  - Microvillar cells (MCs) have been identified in the olfactory epithelium of
      various mammalian species from rodents to humans. Studies on properties and
      functions of MCs to date have yielded partially controversial results, supporting
      alternatively an epithelial or a neuronal nature of these cells. In the present
      study, single and double immunolabeling investigations were carried out using
      antibodies against cytoskeletal and integral membrane proteins in order to
      further characterize MCs in rat and mouse olfactory epithelium. Application of
      antibodies against ankyrin (ANK), a protein that links integral membrane proteins
      to the submembrane cytoskeleton, led to intense labeling of the basolateral
      membranes of numerous cells with characteristic MC morphology. ANK-immunoreactive
      (ir) cells bore an apical tuft of beta-actin-ir microvilli, were filled with
      cytokeratin 18 (CK18)-ir filamentous network, and extended a basal process that
      appeared to end above the basal membrane. Immunoreactions for villin, an actin
      crosslinking protein particularly prominently expressed in brush cells in the
      gastrointestinal and respiratory tract epithelia, and for the alpha-subunit of
      sodium-potassium ATPase (Na(+), K(+)-ATPase), revealed that ANK-ir MCs fall into
      two subpopulations. The less frequent type I MCs displayed villin
      immunoreactivity in their apical microvilli and underneath the basolateral
      membranes; the more numerous type II MCs were negative for villin but possessed
      intense basolateral immunoreactivity for Na(+), K(+)-ATPase. Strong reactivity
      for the epithelial-type integral membrane protein of adherens junctions, E
      Cadherin, was localized in basolateral membranes of both types of MCs. Our
      results support an epithelial nature of ANK-ir MCs in rat and mouse olfactory
      epithelium. Type I MCs strongly resemble brush cells in their immunocytochemical
      characteristics, namely, their ANK reactivity, CK18 reactivity, and villin
      reactivity. The intense Na(+), K(+)-ATPase reactivity of type II MCs implicates
      these cells in transport processes.

PMID- 15856280
TI  - Expression of the human erythroid Rh glycoprotein (RhAG) enhances both NH3 and
      NH4+ transport in HeLa cells.
AB  - The erythroid Rh-associated glycoprotein (RhAG) is strictly required for the
      expression of the Rh blood group antigens carried by Rh (D,CE) proteins. A
      biological function for RhAG in ammonium transport has been suggested by its
      ability to improve survival of an ammonium-uptake-deficient yeast. We
      investigated the function of RhAG by studying the entry of NH3/NH4+ in HeLa cells
      transiently expressing the green fluorescent protein (GFP)-RhAG fusion protein
      and using a fluorescent proton probe to measure intracellular pH (pHi). Under
      experimental conditions that reduce the intrinsic Na/H exchanger activity,
      exposure of control cells to a 10 mM NH4Cl- containing solution induces the
      classic pHi response profile of cells having a high permeability to NH3 (PNH3)
      but relatively low permeability to NH4+ (PNH4). In contrast, under the same
      conditions, the pHi profile of cells expressing RhAG clearly indicated an
      increased PNH4, as evidenced by secondary reacidification during NH4Cl exposure
      and a pHi undershoot below the initial resting value upon its removal.
      Measurements of pHi during methylammonium exposure showed that RhAG expression
      enhances the influx of both the unprotonated and ionic forms of methylammonium.
      Using a mathematical model to adjust passive permeabilities for a fit to the pHi
      profiles, we found that RhAG expression resulted in a threefold increase of PNH4
      and a twofold increase of PNH3. Our results are the first evidence that the human
      erythroid RhAG increases the transport of both NH3 and NH4+.

PMID- 15856281
TI  - Systemic induction of volatile release in cotton: how specific is the signal to
      herbivory?
AB  - Plants attacked by herbivorous insects release chemical signals that attract
      natural enemies of the herbivores to the damaged plants. Feeding of Spodoptera
      exigua larvae on the lower leaves of cotton (Gossypium hirsutum L.) for multiple
      feeding periods of 9-12 h with a 12 h, interval in between when the caterpillars
      are removed overnight, will induce a systemic release of volatile compounds that
      is comparable to the volatiles released in response to continuous feeding damage
      on the lower leaves for several days. The systemic volatile release in response
      to herbivory can be mimicked by mechanically damaging the lower leaves and
      applying caterpillar oral secretion to the injured leaves over 4 days. Cotton
      plants that are only mechanically damaged systemically release significantly less
      beta-pinene, myrcene, (Z)-3-hexenyl acetate, (E)-beta-farnesene and (E,E)-alpha
      farnesene after 4 days compared to plants damaged mechanically with application
      of caterpillar regurgitant. However, multiple 9-12 h mechanical damage alone
      induces a significantly higher systemic release of (Z)-3-hexenyl acetate,
      myrcene, (E)-beta-ocimene, and (E)-beta-farnesene after 4 days compared to
      undamaged control plants. This indicates that multiple mechanical damage alone
      cannot mimic completely the response induced by mechanically injuring the leaves
      and applying caterpillar regurgitant. A specific elicitor in the regurgitant of
      the caterpillar enhances the amount of several systemically released volatiles.
      Thus, the systemic release of volatile compounds by herbivore-damaged cotton
      plants appears to be regulated by at least two different mechanisms.

PMID- 15856282
TI  - Localization of actin filaments on mitotic apparatus in tobacco BY-2 cells.
AB  - Actin filaments are among the major components of the cytoskeleton, and
      participate in various cellular dynamic processes. However, conflicting results
      had been obtained on the localization of actin filaments on the mitotic apparatus
      and their participation in the process of chromosome segregation. We demonstrated
      by using rhodamine-phalloidin staining, the localization of actin filaments on
      the mitotic spindles of tobacco BY-2 cells when the cells were treated with
      cytochalasin D. At prophase, several clear spots were observed at or near the
      kinetochores of the chromosomes. At anaphase, the actin filaments that appeared
      to be pulling chromosomes toward the division poles were demonstrated. However,
      as there was a slight possibility that these results might have been the
      artifacts of cytochalasin D treatment or the phalloidin staining, we analyzed the
      localization of actin filaments at the mitotic apparatus immunologically. We
      cloned a novel BY-2 alpha-type actin cDNA and prepared a BY-2 actin antibody. The
      fluorescence of the anti-BY-2 actin antibody was clearly observed at the mitotic
      apparatus in both non-treated and cytochalasin D-treated BY-2 cells during
      mitosis. The facts that similar results were obtained in both actin staining with
      rhodamine-phalloidin and immunostaining with actin antibody strongly indicate the
      participation of actin in the organization of the spindle body or in the process
      of chromosome segregation. Furthermore, both filamentous actin and spindle bodies
      disappeared in the cells treated with propyzamide, which depolymerizes
      microtubules, supporting the notion that actin filaments are associated with
      microtubules organizing the spindle body.

PMID- 15856283
TI  - Transgenic expression of a novel M. truncatula phytase gene results in improved
      acquisition of organic phosphorus by Arabidopsis.
AB  - A full-length cDNA encoding an extracellular form of phytase was isolated from
      the model legume Medicago truncatula. The phytase cDNA (MtPHY1) has an open
      reading frame of 1,632 bp predicted to encode 543 amino acids including an N
      terminal signal peptide of 27 amino acids. The MtPHY1 gene is 5,151 bp in length,
      containing 7 exons and 6 introns. MtPHY1 transcripts were detected in leaves and
      roots and levels elevated in roots during growth in low phosphate conditions.
      Transgenic Arabidopsis lines expressing MtPHY1 under the control of the root
      specific MtPT1 promoter or the constitutive CaMV35S promoter were created.
      Phytase activities in root apoplast of the transgenic Arabidopsis were 12.3- to
      16.2-fold higher than those of the control plants. The expressed phytase was
      secreted into the rhizosphere as demonstrated by enzyme activity staining and
      HPLC analysis of phytate degradation by root exudates. Transgenic expression of
      the MtPHY1 led to significant improvement in organic phosphorus utilization and
      plant growth. When phytate was supplied as the sole source of phosphorus, dry
      weight of the transgenic Arabidopsis lines were 3.1- to 4.0-fold higher than the
      control plants and total phosphorus contents were 4.1- to 5.5-fold higher than
      the control. Transgenic expression of phytase genes of plant origin has great
      potential for improving plant phosphorus acquisition and for phytoremediation.

PMID- 15856284
TI  - Localization of ferruginol, a diterpene phenol, in Cryptomeria japonica heartwood
      by time-of-flight secondary ion mass spectrometry.
AB  - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was applied to the
      investigation of heartwood extractives in Sugi (Cryptomeria japonica). Sugi
      heartwood tissue generated secondary ions that were not produced from sapwood
      tissue by TOF-SIMS. Among the peculiar ions generated from heartwood, two
      positive ions of m/z 285 and 301 were remarkable due to their appearance in a
      larger mass range and with a high intensity. These two ions were not generated
      from heartwood tissue preextracted with n-hexane, and the n-hexane extract of
      Sugi heartwood produced both ions. Gas chromatography-mass spectrometry of the n
      hexane extract demonstrated that ferruginol, a diterpene phenol, the molecular
      weight of which is 286, constituted one of the predominant constituents of the
      extract. Authentic ferruginol also generated both ions by TOF-SIMS. The molecular
      formula of the m/z 285 ion generated from Sugi heartwood tissue was estimated to
      be C(20)H(29)O, which corresponds well with that of ferruginol, i.e. C(20)H(30)O,
      by peak identification. All these results strongly suggest that the m/z 285 ion
      generated from Sugi heartwood tissue originated significantly from ferruginol in
      Sugi heartwood. By TOF-SIMS imaging, the m/z 285 ion was detected uniformly in
      the tracheid cell walls, in the cell walls of the axial parenchyma cells and ray
      parenchyma cells, and also inside these parenchyma cells. These results indicate
      that ferruginol was distributed almost evenly in Sugi heartwood tissue.

PMID- 15856285
TI  - False memory following rapidly presented lists: the element of surprise.
AB  - This article examines a false memory phenomenon, the Deese-Roediger-McDermott
      (DRM) effect, consisting of high false alarms for a prototype word (e.g., SLEEP)
      following a study list consisting of its associates (NIGHT, DREAM, etc.). This
      false recognition is thought to occur because prototypes, although not presented
      within a study list, are highly activated by their semantic association with
      words that are in the list. The authors present an alternative explanation of the
      effect, based on the discrepancy-attribution hypothesis. According to that
      account, false (and true) familiarity results when a comparison between
      expectations and outcomes within a processing episode causes surprise. Experiment
      1 replicates the DRM effect. Experiment 2 shows that a similar effect can occur
      when participants are shown lists of unrelated words and are then surprised by a
      recognition target. Experiments 3 and 4 show that the DRM effect itself is
      abolished when participants are prevented from being surprised by prototypes
      presented as recognition targets. It is proposed that the DRM effect is best
      understood through the principles of construction, evaluation, and attribution.

PMID- 15856286
TI  - Attentional load and implicit sequence learning.
AB  - A widely employed conceptualization of implicit learning hypothesizes that it
      makes minimal demands on attentional resources. This conjecture was investigated
      by comparing learning under single-task and dual-task conditions in the
      sequential reaction time (SRT) task. Participants learned probabilistic
      sequences, with dual-task participants additionally having to perform a counting
      task using stimuli that were targets in the SRT display. Both groups were then
      tested for sequence knowledge under single-task (Experiments 1 and 2) or dual
      task (Experiment 3) conditions. Participants also completed a free generation
      task (Experiments 2 and 3) under inclusion or exclusion conditions to determine
      if sequence knowledge was conscious or unconscious in terms of its access to
      intentional control. The experiments revealed that the secondary task impaired
      sequence learning and that sequence knowledge was consciously accessible. These
      findings disconfirm both the notion that implicit learning is able to proceed
      normally under conditions of divided attention, and that the acquired knowledge
      is inaccessible to consciousness. A unitary framework for conceptualizing
      implicit and explicit learning is proposed.

PMID- 15856287
TI  - Sequence learning under dual-task conditions: alternatives to a resource-based
      account.
AB  - In two experiments with the serial reaction-time task, participants were
      presented with deterministic or probabilistic sequences under single- or dual
      task conditions. Experiment 1 showed that learning of a probabilistic structure
      was not impaired over a first session by performing a counting task, but that
      such an interference arose over a second session, when the knowledge was tested
      under single-task conditions. In contrast, the effects of the secondary task
      arose earlier for participants exposed to deterministic sequences. This
      difference between deterministic and probabilistic sequences disappeared in
      Experiment 2, where the counting task was performed on tones associated to the
      locations. Comparisons between sessions indicated that the secondary task
      affected not only the expression but also the acquisition of sequence learning,
      and that greater interference was observed in those conditions that yielded more
      explicit knowledge. These results suggest that the effects of a dual task on the
      measures of implicit sequence learning may be partly due to the intrusion of
      explicit knowledge and partly due to the disruption of the sequence produced by
      the inclusion of random events.

PMID- 15856288
TI  - The consciousness continuum: from "qualia" to "free will".
AB  - The consciousness continuum is seen as extending from simple sensory experiences
      to complex subjective constructions resulting in the apparent exercise of
      conscious will. The phenomena between these two extremes include spontaneously
      occurring mental contents, unintended perceptual experiences, memory retrievals,
      and problem solving including feedback of conscious contents. Two factors
      describe this continuum: The presence or absence of intention (psychologically
      defined) and the complexity of the cognitive construction involved. Among other
      benefits, such an analysis is intended to provide an alternative to metaphysical
      and vague concepts such as qualia, free will, and intentionality.

PMID- 15856289
TI  - Working memory and flexibility in awareness and attention.
AB  - We argue that attention and awareness form the basis of one type of working
      memory storage. In contrast to models of working memory in which storage and
      retrieval occur effortlessly, we document that an attention-demanding goal
      conflict within a retrieval cue impairs recall from working memory. In a
      conceptual span task, semantic and color-name cues prompted recall of four
      consecutive words from a twelve-word list. The first-four, middle-four, and final
      four words belonged to different semantic categories (e.g., body parts, animals,
      and tools) and were shown in different colors (e.g., red, blue, and green). In
      Experiment 1, the color of the cue matched that of cued items 75% of the time,
      and the rare mismatch impaired recall. In Experiment 2, though, the color of the
      cue matched that of the cued items only 25% of the time, and the now-more
      frequent mismatches no longer mattered. These results are difficult to explain
      with passive storage alone and indicate that a processing difficulty impedes
      recall from working memory, presumably by distracting attention away from its
      storage function.

PMID- 15856290
TI  - Unlearning a stimulus-response association.
AB  - After a response has been associated with a particular stimulus, would this
      association be "unlearned" when the circumstances call for a new response to be
      made to that stimulus? This question was investigated in the present study with a
      negative priming (NP) paradigm developed by Shiu and Kornblum (1996). In the
      study, participants first practiced with a particular pairing of stimuli and
      responses in a four-choice reaction time (RT) task. Then, in the transfer phase,
      they switched to a different pairing of the same set of stimuli and responses.
      The results showed that a transfer response was slow if this response and the
      stimulus in the preceding trial had been paired in the training phase. Such NP
      effects persisted even after extended practice with the new pairing, suggesting
      that the "old" stimulus-response (SR) associations remain despite acquisition of
      some "new" associations.

PMID- 15856291
TI  - Pending intentions: effects of prospective task encoding on the performance of
      another task.
AB  - A number of recent studies casts doubt on the empirical separability of processes
      of task preparation from the actual execution of the respective task. We report
      two experiments in which we separated the precueing of a task from its execution
      by an intervening task. In addition, for the precued task we employed imperative
      stimuli that in most cases were associated with a competing task, making the
      execution of this task dependent on an internal representation of the information
      provided by the precue. Under these conditions, the performance of the
      intervening task suffered specific interference as a function of its relation to
      the precued task. This suggests that the encoding of the precue resulted in
      specific preparation for the precued task. Furthermore, the transition between
      the intervening task and the precued task was associated with relatively small
      costs that did not vary as a function of the interval that separated the two
      tasks. This also suggests that a great deal of preparation for the second task
      already took place during the encoding of the precue. Further observations
      suggest that the resolution of the interference between a memory-based task
      representation, as well as a perceptually induced task representation, and the
      representation of the currently relevant task took place on the level of
      individual task features.

PMID- 15856292
TI  - NF-kB in development and progression of human cancer.
AB  - The nuclear factor kB (NF-kB) comprises a family of transcription factors
      involved in the regulation of a wide variety of biological responses. NF-kB plays
      a well-known function in the regulation of immune responses and inflammation, but
      growing evidences support a major role in oncogenesis. NF-kB regulates the
      expression of genes involved in many processes that play a key role in the
      development and progression of cancer such as proliferation, migration and
      apoptosis. Aberrant or constitutive NF-kB activation has been detected in many
      human malignancies. In recent years, numerous studies have focused on elucidating
      the functional consequences of NF-kB activation as well as its signaling
      mechanisms. NF-kB has turned out to be an interesting therapeutic target for
      treatment of cancer.

PMID- 15856293
TI  - Vascular endothelial growth factor in salivary pleomorphic adenomas: one of the
      reasons for their poorly vascularized stroma.
AB  - To better understand the poorly vascularized background of the stroma of
      pleomorphic adenomas, we attempted to determine the expression of molecules
      related to blood vessels and hypoxic conditions in pleomorphic adenoma. Surgical
      specimens and tumor cells in primary culture of salivary pleomorphic adenomas
      were used for immunohistochemistry for CD31, vascular endothelial growth factor
      (VEGF) and its receptors Flk-1 and Flt-1, as well as for hypoxia markers, such as
      hypoxia-inducible factor-1alpha (HIF-1alpha) and lactate dehydrogenase-1 (LDH).
      At the same time, alternative splicing modes of the VEGF gene and expression
      levels of the HIF-1alpha gene were analyzed in surgical specimens by means of
      reverse-transcription polymerase chain reaction (RT-PCR) and direct sequencing of
      the PCR products. In addition to co-immunolocalization with CD31+ vascular
      endothelial cells, VEGF and its receptors were demonstrated in normal duct
      epithelial and myoepithelial cells as well as in tumor cells in ductal structures
      and in myxochondroid stromata. Immunolocalizations for HIF-1alpha and LDH were
      confirmed in the VEGF-positive area. Immunofluorescence signals for VEGF and
      others were confirmed in pleomorphic adenoma cells in culture. RT-PCR results
      showed that there were at least four splicing modes of the VEGF gene, among which
      VEGF(121) was most enhanced, and higher HIF-1alpha levels in pleomorphic
      adenomas. The results suggest that pleomorphic adenoma cells produce VEGF in
      several functional forms for their own proliferation or differentiation, and that
      the VEGF expression is controlled by hypoxic circumstances of poorly vascularized
      pleomorphic adenomas.

PMID- 15856294
TI  - Intestinal Behcet disease presenting as neonatal onset chronic diarrhea in an 11
      month-old male baby.

PMID- 15856295
TI  - The abnormalities of carbohydrate metabolism in Turner syndrome: analysis of risk
      factors associated with impaired glucose tolerance.
AB  - An oral glucose tolerance test (OGTT) was performed in 103 patients with Turner
      syndrome (TS) who had normal fasting and postprandial glucose levels. The plasma
      glucose, insulin, C-peptide and proinsulin levels were measured every 30 min
      during the test. Using a homeostatic model assessment (HOMA) and a quantitative
      insulin sensitivity check index (QUICKI), the insulin resistance in TS patients
      was investigated. Diabetes mellitus and impaired glucose tolerance (IGT) were
      newly diagnosed in two and 18 patients respectively. There was a significant
      increase in mean plasma glucose, insulin, C-peptide and proinsulin response
      during an OGTT in the IGT group in contrast to the normal glucose tolerance (NGT)
      group ( P < 0.05). There was a significant decrease in the quantitative insulin
      sensitivity check index (QUICKI) in the IGT group in contrast to the NGT group (
      P < 0.05). The fasting insulin and triglyceride levels strongly predicted the 2 h
      glucose level during the OGTT ( P < 0.05). CONCLUSION: The oral glucose tolerance
      test is superior to the fasting and postprandial plasma glucose test for the
      early detection of abnormalities of carbohydrate metabolism in patients with
      Turner syndrome.

PMID- 15856296
TI  - Expression of caveolin-1 and its correlation with cisplatin sensitivity in oral
      squamous cell carcinoma.
AB  - PURPOSE: Cisplatin (CDDP) is widely used for chemotherapy of oral squamous cell
      carcinoma (OSCC). However, the mechanism of resistance to CDDP is unclear.
      Recently, caveolin-1 was identified as being associated with both metastasis and
      multidrug resistance. In the present study, we showed that caveolin-1 expression
      is significantly related to chemosensitivity in OSCC. METHODS: We established a
      CDDP-resistant cell line, H-1R, from the parental OSCC cell line, H-1. Caveolin-1
      expression was determined by reverse transcriptase-polymerase chain reaction (RT
      PCR) in both cell lines. We analyzed expression of caveolin-1 in 30 OSCC biopsy
      specimens and investigated the relationship between expression of caveolin-1 and
      patients' clinicopathological parameters and chemotherapeutic responses. RESULTS:
      The 3-(3,4-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
      indicated that H-1R has a ten-times greater resistance to CDDP than H-1 has. The
      level of caveolin-1 expression in H-1R was significantly decreased in comparison
      with that in H-1 by real-time RT-PCR analysis. Positive caveolin-1 immunostaining
      correlated positively with a complete response (16/20, 80.0%). However, negative
      immunostaining was found in 6/7 (85.7%) cases with no response. Positive
      immunohistochemical staining of caveolin-1 correlated positively with
      chemosensitivity to CDDP-based combination chemotherapy (P=0.02). CONCLUSIONS:
      These results suggest that overexpression of the caveolin-1 gene may provide
      novel diagnostic markers associated with CDDP sensitivity in OSCC.

PMID- 15856297
TI  - Evaluation of glucocorticoid sensitivity in 697 pre-B acute lymphoblastic
      leukemia cells after overexpression or silencing of MAP kinase phosphatase-1.
AB  - PURPOSE: To determine the effect of modulating MAP kinase phosphatase-1 (MKP-1)
      expression levels on cell death induced by glucocorticoid (GC) or hydroxyurea
      (HU) treatment in the human pre-B acute lymphoblastic leukemia cell line 697.
      METHODS: Stable MKP-1 overexpressing transformants of the 697 pre-B acute
      lymphoblastic leukemia cell line were created and tested for sensitivity to the
      GC triamcinolone acetonide (TA) and HU, and compared to a control 697 cell line
      containing normal MKP-1 expression levels. Small interfering RNAs (siRNAs) were
      designed to inhibit MKP-1 expression and evaluated for their effect on GC
      mediated cell death. RESULTS: MKP-1 overexpression caused a phenotype of partial
      resistance to HU-induced apoptosis but not to GC-induced apoptosis.
      Electroporation of siRNAs effectively silenced MKP-1 expression, and increased
      sensitivity to TA by 9.6+/-1.9%. CONCLUSIONS: Because MKP-1 protects certain
      tumor cells from chemotherapy-induced apoptosis, its inhibition is being
      considered as a possible strategy for combination cancer therapy. However, this
      study suggests that while MKP-1 inhibition may improve the efficacy of DNA
      damaging agents, it may have only limited utility in combination with
      glucocorticoids.

PMID- 15856298
TI  - Multidrug resistance markers P-glycoprotein, multidrug resistance protein 1, and
      lung resistance protein in non-small cell lung cancer: prognostic implications.
AB  - PURPOSE: The aim of this retrospective study was to comparatively investigate the
      expression of the three drug-resistance genes P-glycoprotein (P-gp), multidrug
      resistance protein 1 (MRP1), and lung resistance protein (LRP), in non-small cell
      lung cancer (NSCLC) tissues, and to assess possible associations with
      clinicopathologic features. METHODS: Tumor specimens from 126 patients were
      analyzed by immunohistochemistry and, in selected cases, by reverse transcriptase
      polymerase chain reaction (RT-PCR), and data were statistically analyzed by SPSS.
      RESULTS: The mean expression levels of tumor tissues in the case of P-gp and LRP
      did not exceed the one of normal epithelia, while MRP1 was significantly enhanced
      in NSCLC. A weak association was observed between higher grading and P
      glycoprotein expression (p <0.08) as well as lower grading and MRP1 expression in
      the case of adenocarcinoma (p <0.05). MRP1 levels were highest in TNM stage I and
      declined with advanced stage (p <0.03). A significant association was found
      between high MRP1 levels and longer overall survival (N =115, p <0.04), which was
      highly significant in the patient group never treated with chemotherapy (N =77; p
      <0.007). P-gp expression was enhanced in those patients who had received
      chemotherapy before surgery (p <0.05). CONCLUSIONS: Our data point towards a
      major role of MRP1 in the intrinsic treatment resistance of NSCLC and suggest, in
      addition, a significant activation of P-gp expression during chemotherapy.

PMID- 15856299
TI  - Deletion in chromosome 11 and Bcl-1/Cyclin D1 alterations are independently
      associated with the development of uterine cervical carcinoma.
AB  - PURPOSE: The aim of this study was to understand whether there is any association
      between specific deleted regions in chromosome 11 (chr.11) and alteration
      (amplification/rearrangement) of Bcl-1/Cyclin D1 locus, located at 11q13, in
      uterine cervical carcinoma (CA-CX). METHODS: The deletion mapping of chr.11 was
      studied using 17 highly polymorphic microsatellite markers in 65 primary uterine
      cervical lesions. The Bcl-1/Cyclin D1 alterations were analyzed by Southern blot
      and/or polymerase chain reaction (PCR) method in respective cervical lesions.
      RESULTS: Chr.11 deletion was found to be significantly associated with
      progression of CA-CX. High frequency (48-65%) of deletion was found in 11p15.5
      (D1), 11q22.3-23.1(D2), and 11q23.3-24.1(D3) regions and significant association
      was seen among deletions in D2 and D3 regions. Bcl-1/Cyclin D1 locus alteration
      was observed in overall 27% cervical lesions. Co-amplification of Bcl-1/Cyclin D1
      locus was seen in 10% samples. However, no association was found between the
      deleted regions and Bcl-1/Cyclin D1 locus alterations. CONCLUSIONS: Our study
      suggests that there is no co-operativity between the deleted regions (D1- D3) in
      chr.11 and Bcl-1/Cyclin D1 alterations, but these alterations may provide
      cumulative effect in progression of the tumor. The D1-D3 regions may harbor
      candidate tumor suppressor gene(s) (TSGs) associated with the development of CA
      CX.

PMID- 15856300
TI  - Seasonal dynamics of Trichodina spp. on whiting (Merlangius merlangus)in relation
      to organic pollution on the eastern Black Sea coast of Turkey.
AB  - It was determined that there is a relationship between prevalence and mean
      densities of Trichodina spp. on Merlangius merlangus and organic pollution,
      measured as levels of nitrite, nitrate and phosphate in the surrounding
      environment. Monthly, two left anterior gill arcs of 60 M. merlangus (unless
      otherwise stated) captured with hook and line were fixed in 10% formalin. The
      number of Trichodina spp. was determined by counting all of the cells with a grid
      slide. The two right anterior gill arcs were used to prepare dry smears to
      picture the morphology of the trichodinids and to determine species composition.
      High levels of prevalence and densities of the protozoan were observed during the
      late fall, winter and early spring months. Then, prevalence decreased to lower
      levels but never below 60%, an indication of the important role of M. merlangus
      for Trichodina spp. in the studied region. A multivariate analysis revealed that
      the magnitude of prevalence was related to the level of all three parameters:
      nitrite, nitrate and phosphate (r2=0.59). However, a much stronger relationship
      between prevalence and nitrate, phosphate, oxygen and temperature (r2=0.89) was
      detected. Consequently, the seasonal parasite prevalence and density were
      affected by organic pollution. The timing for a high prevalence and mean
      densities of this parasite also suggests that primary production may be
      responsible for the observed seasonal variation in prevalence and mean densities.
      By using the model describing the relationship between the water quality
      parameters and the prevalence data of Trichodina spp. recalculated values and
      observed field data corresponded closely.

PMID- 15856301
TI  - Immunolocalisation of an ABC transporter, P-glycoprotein, in the eggshells and
      cuticles of free-living and parasitic stages of Haemonchus contortus.
AB  - Recent data have suggested that P-glycoprotein (Pgp), working as membrane efflux
      "pumps", plays a major role in the transport of anthelmintic drugs in parasitic
      nematodes of ruminants. Flow cytometry analyses has shown that active Pgp is
      probably present in the external layers of Haemonchus contortus eggshells,
      following staining with the mouse monoclonal anti-human MDR1 antibody UIC2, which
      binds to Pgp in its active conformation. We evaluated the presence and
      distribution of this protein in the envelopes (eggshells and cuticles) of H.
      contortus and compared the various stages (eggs, L1-L2 larvae, L3 larvae, adult
      male and female worms). Electrophoresis revealed a 170-kDa band, corresponding to
      the molecular weight of Pgp in all stages. Indirect immunofluorescence staining
      with UIC2 showed Pgp to be located in the external layer of eggshells or
      cuticles. Transmission electron microscopy was used to localise Pgp more
      accurately in the three layers of the eggshells and cuticles. The conformation
      and biological functions of this protein, which we did not expect to find in such
      structures, remain to be determined.

PMID- 15856302
TI  - Humoral and cellular immune responses in BALB/c and C57BL/6 mice immunized with
      cytoplasmic (CRA) and flagellar (FRA) recombinant repetitive antigens, in acute
      experimental Trypanosoma cruzi infection.
AB  - In previous studies, cytoplasmic repetitive antigen (CRA) and flagellar
      repetitive antigen (FRA) proteins induced specific humoral and cellular immune
      responses in susceptible and resistant mice in the absence of Trypanosoma cruzi
      infection with a significant induction of the Interferon-gamma (IFN-gamma)
      production in those animals. In this follow-up paper, the immunostimulatory and
      protective effects of these proteins were evaluated by immunizing with CRA or FRA
      antigens, BALB/c and C57BL/6 mice and challenging with a T. cruzi (Y strain).
      Both proteins induced humoral response with high levels of IgG isotypes as well
      as cellular immunity with high levels of IFN-gamma when compared to controls.
      However, the lymphocyte proliferative response was minimal. The survival rate at
      30 days post-infection was significant in CRA (60%) or FRA (50%)--immunized
      BALB/c mice and CRA (83.3%)--immunized C57BL/6 mice. Taken as a whole these
      findings indicate that CRA and FRA are immunogenic and potentially important for
      protective immunity.

PMID- 15856303
TI  - Functional constraint and divergence in the G protein family in Caenorhabditis
      elegans and Caenorhabditis briggsae.
AB  - Part of the challenge of the post-genomic world is to identify functional
      elements within the wide array of information generated by genome sequencing.
      Although cross-species comparisons and investigation of rates of sequence
      divergence are an efficient approach, the relationship between sequence
      divergence and functional conservation is not clear. Here, we use a comparative
      approach to examine questions of evolutionary rates and conserved function within
      the guanine nucleotide-binding protein (G protein) gene family in nematodes of
      the genus Caenorhabditis. In particular, we show that, in cases where the
      Caenorhabditis elegans ortholog shows a loss-of-function phenotype, G protein
      genes of C. elegans and Caenorhabditis briggsae diverge on average three times
      more slowly than G protein genes that do not exhibit any phenotype when mutated
      in C. elegans, suggesting that genes with loss of function phenotypes are subject
      to stronger selective constraints in relation to their function in both species.
      Our results also indicate that selection is as strong on G proteins involved in
      environmental perception as it is on those controlling other important processes.
      Finally, using phylogenetic footprinting, we identify a conserved non-coding
      motif present in multiple copies in the genomes of four species of
      Caenorhabditis. The presence of this motif in the same intron in the gpa-1 genes
      of C. elegans, C. briggsae and Caenorhabditis remanei suggests that it plays a
      role in the regulation of gpa-1, as well as other loci.

PMID- 15856304
TI  - Proteomic analysis reveals the wide-ranging effects of the novel, iron-responsive
      regulator RirA in Rhizobium leguminosarum bv. viciae.
AB  - The wide-ranging effects of RirA, a novel Fe-responsive regulator of gene
      expression in Rhizobium leguminosarum bv. viciae, were monitored on 2D gels.
      Approximately 100 proteins were expressed at higher levels in a RirA(-) mutant,
      compared to wild type. These included the products of the sufS(2)BCDS(1)XA
      operon, which probably specifies the synthesis of [FeS] clusters. Using lac
      fusions, this operon was confirmed to be regulated by RirA in response to Fe
      availability. Genes for some ABC transporters, and a protein that may be involved
      in making a phenazine-like molecule, were also repressed by Fe in a RirA
      dependent way. Strikingly, at least 17 proteins were reduced in abundance in the
      RirA(-) mutant. These included three ABC transporters, a GatB-like enzyme
      involved in tRNA modification, and a protein that may confer bacteriocin
      resistance. As judged by lac reporter fusions, this apparently positive control
      by RirA was probably due to post-transcriptional effects, in at least some cases.
      Therefore, although RirA shows no sequence similarity to Fur or DtxR, it
      functions as a wide-ranging, Fe-responsive regulator.

PMID- 15856305
TI  - A mutation within the saposin D domain in a Gaucher disease patient with normal
      glucocerebrosidase activity.
AB  - Only two Gaucher disease (GD) patients bearing mutations in the prosaposin gene
      (PSAP), and not in the glucocerebrosidase gene (GBA), have been reported. In both
      cases, one mutant allele remained unidentified. We report here the identification
      of the second mutation in one of these patients, being the first complete
      genotype described so far in a SAP-C-deficient GD patient. This mutation,
      p.Q430X, is the first one reported in the saposin D domain and probably produces
      a null allele by nonsense mediated mRNA decay.

PMID- 15856306
TI  - Prior injury accelerates subsequent wound closure in a mouse model of
      regeneration.
AB  - Tissue regeneration and scarless healing involves the complete replacement and
      functional restoration of damaged organs and tissues. In this study of the
      "scarless healing" MRL mouse model, we demonstrate that 2-mm diameter through-and
      through holes made in the cartilaginous part of previously injured MRL mouse ears
      are closed more efficiently, and that the regenerative repair response is
      significantly accelerated compared with unprimed MRL and control "nonhealer"
      strains of mice. Accelerated healing was detected both locally and distally from
      the original site of injury indicating the involvement of systemic components
      such as circulating cell types or soluble factors. Histologically, we observed
      early differences during the wound repair process (before Day 4 post injury) with
      accelerated formation of blastema-like structures, epidermal downgrowths, and
      enhanced epithelium thickening in wound border zones in primed MRL mice versus
      unprimed MRL mice. Although the mechanism of tissue regeneration remains unclear,
      the results from this study justify the use of the MRL model for further
      experimentation directed toward the identification of proteins and cell types
      capable of stimulating scarless tissue regeneration.

PMID- 15856307
TI  - Gene expression, cellular localization, and enzymatic activity of diacylglycerol
      kinase isozymes in rat ovary and placenta.
AB  - Female reproductive organs show remarkable cyclic changes in morphology and
      function in response to a combination of hormones. Evidence has accumulated
      suggesting that phosphoinositide turnover and the consequent diacylglycerol (DG)
      protein kinase C (PKC) pathway are intimately involved in these mechanisms. The
      present study has been performed to investigate the gene expression, cellular
      localization, and enzymatic activity of the DG kinase (DGK) isozymes that control
      the DG-PKC pathway. Gene expression for DGKalpha, -epsilon, -zeta, and -iota was
      detected in the ovary and placenta. Intense expression signals for DGKzeta and 
      alpha were observed in the theca cells and moderate signals in the interstitium
      and corpora lutea of the ovary. On the other hand, signals for DGKepsilon were
      seen more intensely in granulosa cells. In the placenta, signals for DGKalpha and
      -iota were observed in the junctional zone, whereas those for DGKzeta were
      detected in the labyrinthine zone. At higher magnification, the signals for
      DGKalpha were mainly discerned in giant cytotrophoblasts, and those for DGKiota
      were found in small cytotrophoblasts of the junctional zone. DGKzeta signals were
      observed in all cellular components of the labyrinthine zone, including
      mesenchyme, trabecular trophoblasts, and cytotrophoblasts. DGKepsilon signals
      were detected in the junctional zone on day 13 and 15 of pregnancy and were
      diffusely distributed both in the labyrinthine and junctional zones at later
      stages. The present study reveals distinct patterns of mRNA localization for DGK
      isozymes in the rat ovary and placenta, suggesting that each isozyme plays a
      unique role in distinct cell types in these organs.

PMID- 15856308
TI  - Damage to ovarian development and function.
AB  - Ovarian function in women can be compromised by exposure to toxic environmental
      factors. Chemicals that affect ovarian function can act through direct effects on
      hormone action (ovary) or by interference with steroid hormone action
      (hypothalamus and/or pituitary). These effects can cause problems in the form of
      infertility. Alternatively, ovarian toxicants can directly cause ovarian failure
      by extensive follicular destruction. This targeting can result in loss of ovarian
      steroid hormones, eventual ovarian failure (menopause), and ultimate disruption
      of neuroendocrine feedback causing increased levels of FSH and LH. This article
      provides an overview of chemicals that in animal studies have been identified to
      cause disrupted ovarian function with a focus on the sites of targeting by which
      these disruptions occur. In predicting the impact of environmental factors on
      reproductive function in women, it is critical to gain a better appreciation of
      the physiological consequences resulting from the potential variety of mechanisms
      by which toxicants can disrupt ovarian function. This article attempts to provide
      such a perspective within the context of specific chemicals for which ovarian
      sites of toxicity have been identified.

PMID- 15856309
TI  - Understanding the role of thyroid hormone in Sertoli cell development: a
      mechanistic hypothesis.
AB  - More than a decade of research has shown that Sertoli cell proliferation is
      regulated by thyroid hormone. Neonatal hypothyroidism lengthens the period of
      Sertoli cell proliferation, leading to increases in Sertoli cell number, testis
      weight, and daily sperm production (DSP) when euthyroidism is re-established. In
      contrast, the neonatal Sertoli cell proliferative period is shortened under
      hyperthyroid conditions, but the mechanism by which thyroid hormone is able to
      negatively regulate Sertoli cell proliferation has been unclear. Recent progress
      in the understanding of the cell cycle has provided the opportunity to dissect
      the molecular targets responsible for thyroid-hormone-mediated effects on Sertoli
      cell proliferation. In this review, we discuss recent results indicating a
      critical role for the cyclin-dependent kinase inhibitors (CDKI) p27(Kip1) and
      p21(Cip1) in establishing Sertoli cell number, testis weight, and DSP, and the
      ability of thyroid hormone to modulate these CDKIs. Based on these recent
      results, we propose a working hypothesis for the way in which thyroid hormone
      regulates the withdrawal of the cell cycle by controlling CDKI degradation.
      Finally, although Sertoli cells have been shown to have two biologically active
      thyroid hormone receptor (TR) isoforms, TRalpha1 and TRbeta1, experiments with
      transgenic mice lacking TRalpha or TRbeta illustrate that only one TR mediates
      thyroid hormone effects in neonatal Sertoli cells. Although significant gaps in
      our knowledge still remain, advances have been made toward appreciation of the
      molecular sequence of events that occur when thyroid hormone stimulates Sertoli
      cell maturation.

PMID- 15856310
TI  - Inhibition of p53 during physiological angiogenesis in the hamster ovary does not
      affect extent of new vessel formation but delays vessel maturation.
AB  - Transcription factor p53 regulates the cell cycle and apoptosis and may impair
      angiogenesis by the deregulation of pro-angiogenic factors and the activation of
      anti-angiogenic factors. Our aim has been to elucidate further the role of p53 in
      physiological angiogenesis. By treating hamsters with the wildtype p53 inhibitor
      pifithrin-alpha (PFT) versus equivalent volumes of the vehicle dimethylsulfoxide,
      we showed a reduced p53 tissue protein level, a reduction of poly(ADP-ribose)
      polymerase and cleaved caspase-3 products, and a slightly increased proliferation
      of cell nuclear antigen and cyclin D1 by Western blot protein analysis of ovarian
      tissue. PFT further increased platelet-derived growth factor and did not
      influence vascular endothelial growth factor in female reproductive tissue.
      Despite these differences in tissue levels of proteins potentially involved in
      angiogenesis, in vivo fluorescence-microscopic analysis of freely transplanted
      ovarian follicles revealed comparable kinetics and an extent of revascularization
      with almost identical densities of network microvessels in both groups. However,
      follicles of PFT-treated animals exhibited enlarged diameters and higher
      volumetric blood flow within the newly formed microvessels. Less-dense basement
      membranes with unclear laminar structure and only a loose contact of pericytes to
      endothelial cells were also occasionally found, providing evidence of delayed
      maturation and impaired diameter control of microvessels. Thus, inhibition of
      wildtype p53 during physiological angiogenesis does not affect the extent of new
      vessel formation but may delay the maturation of newly formed microvessels.

PMID- 15856311
TI  - Localization of prolactin receptor in the newt brain.
AB  - In the male newt Cynops pyrrhogaster, prolactin (PRL) acts directly on the
      central nervous system and induces courtship behavior. As a step to elucidate the
      localization of neurons on which PRL acts, we developed a polyclonal antibody
      against an oligopeptide having a sequence completely identical with a part of the
      sequence of PRL receptors (PRLRs) of two species of newts, C. pyrrhogaster and C.
      ensicauda, and performed an immunohistochemical study with this antibody. PRLR
      immunoreactive cells were observed in the medial amygdala, anterior preoptic
      area, magnocellular preoptic nucleus, suprachiasmatic nucleus, nucleus of the
      periventricular organ, ventral hypothalamic nucleus, and choroid plexus. We also
      performed in situ hybridization with a (35)S-labeled newt PRLR antisense RNA
      probe and detected signals in the preoptic area and choroid plexus.
      Colocalization of both PRLR-like immunoreactivity and arginine vasotocin-like or
      mesotocin-like immunoreactivity was demonstrated in the magnocellular preoptic
      nucleus. This is the first report of PRLR localization in the amphibian brain.

PMID- 15856312
TI  - The Alport nephropathy: clinicopathological correlations.
AB  - The alleged dominance of diffuse attenuation of the glomerular basement membrane
      (GBM) in young children and females with Alport's Syndrome (AS) suggests that it
      might be the initial ultrastructural manifestation of type IV collagen defects.
      We carried out a 'blind' review of 130 renal biopsies obtained from 100 patients
      with AS, emphasizing the electron microscopy changes, and related the findings to
      the clinical presentation and outcome. The intracapillary distribution of (1)
      thickened, (2) attenuated and (3) normal GBM was assessed individually as: none
      (grade 0), <25% (grade 1), 25-50% (grade 2) and >50% (grade 3). Deafness was
      defined as persistent loss of > or =30 dBs. Proteinuria was measured as
      protein/creatinine ratios in early morning urine. Heavy proteinuria (> or =200
      mg/mmol) correlated significantly with the presence of segmental and global
      glomerulosclerosis and foam cells. Comparing grades 0+1 vs. 3 GBM changes, using
      a 2x2 chi(2) test, there were significant correlations between grade 3 GBM
      thickening and male sex (P =0.005), heavy proteinuria (P =0.02) and deafness (P
      <0.001). GBM thickening did not correlate with age at the initial biopsy, but
      repeat biopsies demonstrated increasing thickening with age. The grades of GBM
      attenuation did not correlate with either age at biopsy or sex. In 11 biopsies
      with atypical lamina densa changes in thickened GBM segments, there were no
      differences in clinicopathological correlations compared with classical biopsies.
      Our data indicate that diffuse GBM attenuation can be an ultrastructural variant
      of the Alport nephropathy, but do not support the contention that it is the
      initial lesion.

PMID- 15856313
TI  - Chronic kidney disease and inflammation in pediatric patients: from bench to
      playground.
AB  - Signs of an activated immune system can be observed already in the early stages
      of chronic kidney disease (CKD). Markers of a chronically activated immune system
      are closely linked to several complications of CKD, such as accelerated
      atherosclerosis, vascular calcification, insulin resistance, increased muscle
      catabolism, loss of appetite, bone remodeling, and increased peritoneal
      permeability. Interestingly, all the aforementioned pathological states resemble
      a state of accelerated ageing and are strongly associated with increased
      morbidity and mortality in CKD patients. In recent studies, signs of inflammation
      have been shown as predictors for mortality in dialysis patients, and the role of
      inflammation as a risk factor for complications of CKD in children has emerged.
      Although preliminary findings suggest that inflammation is highly prevalent in
      the pediatric population with CKD, information related pathogenic links and to
      clinical outcomes is lacking. For the future, it is crucial for investigations to
      address the mechanisms and complications of inflammation that are manifested in
      pediatric patients with CKD in all stages. Since early identification and
      intervention may generate the most efficient strategies for prevention and
      treatment of cardiovascular disease in CKD patients, the pediatric population
      deserves special attention in future studies. In this review, we discuss the
      mechanisms involved in the inflammatory activation and the main causes and
      consequences of the inflammatory state observed in the CKD patient, with special
      emphasis on the pediatric population.

PMID- 15856314
TI  - Multicystic dysplastic kidney: diagnosis and evolution.

PMID- 15856315
TI  - Comparison of 1-84 and intact parathyroid hormone assay in pediatric dialysis
      patients.
AB  - The non-invasive diagnosis of renal osteodystrophy (ROD) in patients with end
      stage renal disease (ESRD) remains dependent on the determination of an accurate
      parathyroid hormone (PTH) level. Older assays that determine the "intact" PTH
      molecule are known to cross react with various PTH fragments, resulting in
      overestimation of PTH levels. Recently, assays that determine the whole 1-84 PTH
      molecule have been made available. Monthly PTH values in chronic dialysis
      patients at our institution were compared using the Nichols Bio-Intact PTH
      (BiPTH, 1-84 PTH) and the intact PTH (iPTH) assay over 3 consecutive months. One
      hundred twenty-four samples were obtained from 51 (29 male) pediatric dialysis
      patients (27 HD). The mean patient age was 14.2+/-5.6 years (1.8-25.7 years),
      with 12 patients<10 years and 15 patients <30 kg. The mean 1-84 PTH/iPTH ratio
      was 0.48+/-0.11. While BiPTH values correlated closely with iPTH values ( r
      =0.98, P <0.05), we observed significant intra-patient (16.4+/-15.4%; range: 
      73.9 to 67.7%, total % error: 47.2%) and inter-patient (17.2+/-18.9%; range: 
      73.9 to 129.9%, total % error: 55%) variability in the 1-84 PTH/iPTH ratio over
      the 3-month study period. Thus, our findings suggest that ROD management based on
      prior associations between iPTH levels and bone biopsy findings should not be
      extrapolated using the newer 1-84 PTH assay.

PMID- 15856316
TI  - The role of keto acids in the supportive treatment of children with chronic renal
      failure.
AB  - According to the hyperfiltration theory of renal diseases characterized by a
      decrease in the number of functional nephrons, increased arterial blood pressure,
      excessive protein intake in the diet, high levels of calcium (Ca) and phosphorus
      (P), secondary hyperparathyroidism, hypertriglyceridemia and/or
      hypercholesterolemia, proteinuria and metabolic acidosis are some factors that
      impair the prognosis of the disease. The amount of protein in the diet is the
      most important of these factors. A protein-restricted diet administered to
      patients with chronic renal failure results in the risk of inadequate amino acid
      intake. To overcome this problem, the use of dysaminated alpha-keto analogues has
      been considered to reduce the risk of nitrogenemia resulting from the continuous
      intake of essential amino acids. Currently, the necessity of essential amino
      acids even in adult patients with chronic renal failure is controversial;
      besides, trials on the use of these amino acids in pediatric patients are scarce.
      The aim of this study is to investigate the efficacy and applicability of
      conservative therapy with a protein-restricted diet supplemented with keto acids
      in the management of chronic renal insufficiency or failure.

PMID- 15856317
TI  - Familial hematurias: what we know and what we don't.
AB  - Over the past 30 years we have learned a great deal about the molecular genetics
      and natural history of familial forms of hematuria. Our enhanced understanding of
      these conditions has yet to generate effective therapies for Alport syndrome, the
      form of familial hematuria associated with end-stage renal disease. This review
      briefly presents the current state of knowledge about familial hematuria and
      argues for the organization of clinical therapeutic trials in Alport syndrome.

PMID- 15856318
TI  - Twenty-four-hour ambulatory blood pressure monitoring in infants and toddlers.
AB  - During the past several years, 24-hour (24-h) ambulatory blood pressure
      monitoring (ABPM) has become a useful tool for the diagnosis and management of
      children and adolescents with elevated blood pressure (BP). Some reports have
      also provided blood pressure nomograms for particular devices. However, there are
      very few reports of the use of this method in very young children. In our study
      we investigated the applicability of ABPM in 97 healthy infants and toddlers,
      aged from 2 to 30 months. A satisfactory ABPM profile was obtained in 86.6% of
      the children, with an average of 75.0% satisfactory BP recordings. The mean +/-
      SD systolic and diastolic BP of healthy infants and toddlers was 99+/-12/62+/-12
      mmHg during the daytime and 95+/-11/57+/-10 mmHg during the night, with no gender
      difference being observed. The 24-h mean +/- SD systolic and diastolic BP, which
      may be a more appropriate measure of BP in this particular age group, was found
      to be 97+/-12/59+/-11 mmHg. We also confirmed the increase in systolic and
      diastolic BP with increased height (length). There was only a slight nocturnal
      decrease in BP. We conclude that this method is applicable for the assessment of
      blood pressure in very young children.

PMID- 15856319
TI  - Hypomagnesemia with hypercalciuria and nephrocalcinosis: case report and a family
      study.
AB  - A 7-month-old male infant was referred for investigation after a documented
      febrile urinary tract infection. His past medical history was characterized by
      episodes of unexplained fever and mild dehydration. The ultrasound examination of
      his kidneys demonstrated bilateral diffuse medullary nephrocalcinosis. His serum
      and urine biochemistry revealed hypomagnesemia (0.4 mmol/l), hyperuricaemia (506
      micromol/l), mildly increased iPTH (71 pg/ml) and hypercalciuria (16.0
      mg/kg/day). The diagnosis of familial hypomagnesemia with hypercalciuria and
      nephrocalcinosis (FHHNC) was confirmed by mutational analysis of the CLDN16 gene,
      encoding paracellin-1. Sequencing displayed a homozygous Leu151Phe exchange
      affecting the first extracellular loop of paracellin-1. There were eight family
      relatives who underwent biochemical analysis, renal ultrasound and genetic
      investigation for CLDN16 mutations. Five of them were found to be heterozygous
      for the Leu151Phe mutation. Two heterozygotes (the mother and the maternal
      grandfather) presented with hypercalciuria. The grandfather had a history of
      recurrent passage of calculi. These findings point to the role of heterozygous
      CLDN16 gene mutations in renal pathophysiology. In conclusion, patients suspected
      of having FHHNC should be screened for CLDN16 mutations, especially with respect
      to genetic counseling. In addition, heterozygotes at risk should be clinically
      assessed in order to prevent renal complications of hypercalciuria.

PMID- 15856320
TI  - IgG and complement receptor expression in children treated by peritoneal
      dialysis.
AB  - Children treated by peritoneal dialysis (PD) are at increased risk of infections.
      IgG receptors (FcgammaRs) and complement receptors (CRs) on white blood cells
      (WBCs) are important for the phagocytic process. We have investigated FcgammaR
      and CR expression on monocytes, macrophages and neutrophils in blood and in
      peritoneal dialysis effluent (PDE) of 39 PD children. WBCs were isolated from
      blood and PDE, labelled with FITC-conjugated CD16 (FcgammaRIII), CD32
      (FcgammaRII), CD64 (FcgammaRI), CD11b (CR3) and CD35 (CR1) monoclonal antibodies,
      and analysed by flow cytometry. Peritoneal cells had lower percentages of
      FcgammaR-positive or CR-positive cells than blood. On the other hand, the
      receptor number per cell [mean fluorescence intensity (MFI)] was higher on
      peritoneal macrophages and neutrophils than blood, except for CD16. The FcgammaR
      and CR expression in blood and dialysate did not change significantly during the
      first year of PD treatment. During a peritonitis episode the MFI of all receptors
      in blood increased only on monocytes, with the exception of CD32. The percentages
      of FcgammaR-positive and CR-positive macrophages and neutrophils in the PDE
      increased, whereas the MFI did not increase consistently. Peritoneal cells of PD
      children showed a lower percentage of FcgammaR-positive and CR-positive
      neutrophils and macrophages, combined with an increased MFI, indicating a state
      of activation. Blood and peritoneal cells are capable of up-regulating the
      receptor expression during peritonitis but probably not to a maximum level.

PMID- 15856321
TI  - Urinary diversion in children and adolescents with neurogenic bladder: the Mainz
      experience. Part I: Bladder augmentation and bladder substitution--therapeutic
      algorisms.
AB  - After the failure of conservative treatment of neurogenic bladders (deterioration
      of the upper urinary tract/incontinence), bladder augmentation/bladder
      substitution and supravesical urinary diversion have to be considered. In our
      concept, bladder augmentation is indicated for hyperreflexive and small low
      compliance bladders with normal upper urinary tracts. In cases with combined
      sphincteric incompetence, a fascial sling (FS) can be required to achieve
      continence. In patients with small and hyperreflexive bladders, high-grade reflux
      and/or dilatation of the upper tracts, bladder substitution and ureteral
      reimplantation are appropriate. For patients with irreparable sphincter defects
      and those who are unable to perform transurethral self-catheterization, continent
      cutaneous diversion is offered. For patients with chronic renal failure,
      deterioration of the upper urinary tract and those who are not able to perform a
      self-catheterization of a continent stoma, colonic conduit diversion is our
      therapy of choice. The current study aims to investigate the long-term safety of
      our concept for these patients in regard to protecting the upper tracts and
      providing continence. Between 1968 and 2002, 170 children and adolescents
      underwent surgery. Of these, 24 received an orthotopic reservoir (bladder
      augmentation, n =10; combined with FS, n =1; orthotopic bladder substitution with
      ureteral reimplantation, n =14). The material, methods and results of the
      remaining 146 patients are reported in parts II and III. One of the 24 patients
      with an orthotopic reservoir was lost to follow-up. An average follow-up of 9
      years (1.3-18 years; median 8.7 years) was available in 23 patients with 42 RUs.
      As compared to preoperatively, the upper urinary tracts remained stable or
      improved in all ten patients with bladder augmentation and in 20/23 renal units
      (RUs) with bladder substitution at the latest follow-up. Eight of ten patients
      with bladder augmentation are continent. All 13 patients with bladder
      substitution are continent during the day; one requires a safety pad at night.
      Bladder augmentation has been effective in patients with hyperreflexive and small
      low compliance bladders and normal upper urinary tracts. In those with high-grade
      reflux and/or dilatation of the upper tracts, bladder substitution and ureteral
      reimplantation are recommended. In very selected patients a fascial sling (FS)
      can be required to achieve continence.

PMID- 15856322
TI  - Association of vitamin-D and calcitonin receptor gene polymorphism in paediatric
      nephrolithiasis.
AB  - We investigated the role of vitamin-D receptor gene (VDR) and calcitonin receptor
      (CTR) gene polymorphism in childhood nephrolithiasis in the north Indian
      population. A control group of 60 healthy paediatric individuals (age range 4-16
      years) and 50 paediatric patients (age range 2-14 years) with kidney stones were
      examined. Polymorphism in both genes (VDR and CTR) was detected by using PCR
      based restriction analysis. There was a statistically significant difference
      between the two groups for the genotypes of the VDR gene Fok-I polymorphism (P
      =0.007) and the CTR gene (P =0.048) polymorphism. The odds ratio (95% Confidence
      Interval) for the C allele in those at risk of stone disease was 1.83 (0.82-4.09)
      in VDR gene polymorphism and 1.99 (0.90-4.39) in the case of CTR gene
      polymorphism. Our results suggest that the effects of VDR (Fok-I) and CTR gene
      polymorphism contribute to the understanding of the pathogenesis of urinary
      calculi. It is also suggestive of a potential candidate gene in the search for
      genetic causes of paediatric calcium oxalate nephrolithiasis.

PMID- 15856323
TI  - Percutaneous nephrostomy in children: diagnostic and therapeutic importance.
AB  - The aim of this study was to evaluate the effectiveness and safety of
      percutaneous nephrostomy (PN) in terms of diagnostic and therapeutic approach in
      children with urological problems. PN was performed on 39 kidneys in 28 patients
      (12 girls, 16 boys) aged 4.5 months to 13 years (average 5.38+/-3.41 years)
      during the period from January 1996 to December 2003. Underlying abnormalities
      were ureteropelvic junction obstruction (UPJO) in 14 patients (17 kidneys),
      ureterovesical junction obstruction (UVJO) in six patients (eight kidneys),
      supravesical obstruction due to tumour or hydatid cyst or ureteral stone in three
      patients (five kidneys), and severe vesicoureteral reflux (VUR) with/without
      neurogenic bladder associated with pyonephrotic kidneys in five patients (nine
      kidneys). The duration of catheter insertion was between 2 and 160 days (average
      80+/-65.01 days). The complications were haematuria (six cases), infection (five
      cases) and displacement of catheter (four cases). Radical surgical management was
      performed in 25 patients (33 kidneys): pyeloplasty in eight cases (ten kidneys),
      UVJO correction in six cases (eight kidneys), nephrectomy in five cases (five
      kidneys), ureteroneocystostomy in four cases (seven kidneys), hydatid cyst
      operation in one case (two kidneys) and stone extraction in one case (one
      kidney). PN is an easy, safe and efficient diagnostic and therapeutic procedure
      with few complications in childhood.

PMID- 15856324
TI  - Cyclosporin A absorption profiles in children with nephrotic syndrome.
AB  - A single blood concentration measurement of Neoral 2 h after administration (C2)
      is a new concept in therapeutic drug monitoring (TDM). In most adult patients,
      the concentration of cyclosporin A (CyA) peaks within 2 h after Neoral
      administration. Therefore, monitoring the area under the concentration-time curve
      over the first 4 h post-dose (AUC0-4) is considered to be the most reliable
      strategy for Neoral TDM. In addition, C2 is considered to be the most accurate
      predictor of AUC0-4, with which C2 correlates best. Thus, in adult patients, C2
      monitoring is recommended as the best single-point TDM method for Neoral.
      However, in paediatric patients, the effectiveness of C2 monitoring is still
      unclear. We examined the trough concentration (C0), C1, C2, C3, and C4 of CyA in
      60 patients (1 to 20 years old, mean age 7.42+/-0.67 years) who had nephrotic
      syndrome treated with Neoral. The peak concentration of C0-C4 was C1 or C2 in 38
      patients (early peak group) and C3 or C4 in 22 patients (late peak group). C2 in
      the late peak group was significantly lower than that in the early peak group
      (422+/-50.1 vs. 665 +/-53.8 ng/ml, P =0.0008), although the administered doses of
      Neoral and C0 were similar between these groups. Therefore, TDM by C2 using the
      same standard as in the early peak group might result in an overdose of CyA in
      the late peak group. As the concentration peaked at 3 h or more after Neoral
      administration in the late peak group, AUC0-4 does not necessarily reflect the
      Neoral absorption profile. As more than 33% of the paediatric patients were in
      the late peak group, TDM by AUC0-4 or C2 should be used carefully in paediatric
      patients treated with Neoral.

PMID- 15856325
TI  - Bilateral universal nephroblastomatosis in an 8-month-old infant treated with
      chemotherapy.
AB  - We report the case of an 8-month-old female infant presenting with bilateral,
      diffusely enlarged kidneys. A diagnosis of bilateral, universal
      nephroblastomatosis was made on tissue biopsies from both kidneys after
      correlation with the radiological findings. As far as we know, this is the oldest
      patient reported with this diagnosis in the English literature (they are usually
      younger than 4 months). The patient was treated with chemotherapy with very good
      response and almost 1 year later she is showing no signs of recurrence of her
      disease.

PMID- 15856326
TI  - Comparative renal histomorphometry: a case study of oligonephropathy of
      prematurity.
AB  - Children born with very low birth weight have a decreased nephron number. Low
      nephron mass is associated with adult hypertension, proteinuria, and diabetes
      mellitus. The histomorphometry and radial glomerular count (RGC) of a total
      nephrectomy from a child with renal disease associated with extreme prematurity
      was compared with the kidney from a full-term age-matched child of normal
      gestation with chronic renal failure due to focal and segmental
      glomerulosclerosis (FSGS) and to a child without renal disease. Bowman's space
      area, mesangium and mesangial tuft area were determined in 50 glomeruli of each
      specimen by computer-assisted morphometry. RGC was 4 in the ex-preterm child, 8
      in the patient with FSGS, and 9 in normal control. The patient with FSGS had
      larger glomerular area expressed as square micrometers (mum(2)) of Bowman's
      capsule, the mesangium and the mesangial tuft area measurements than the normal
      control and the child born preterm who subsequently developed renal failure had
      significantly larger Bowman's capsule and mesangium than the two controls. This
      case report begins to identify important pathologic findings of decreased nephron
      numbers and glomerulomegaly associated with preterm birth.

PMID- 15856328
TI  - Liddle syndrome caused by P616R mutation of the epithelial sodium channel beta
      subunit.

PMID- 15856327
TI  - Tuberous sclerosis and the kidney: from mesenchyme to epithelium, and beyond.
AB  - The renal manifestations of tuberous sclerosis complex (TSC) are remarkably
      diverse, including polycystic kidney disease, oncocytomas, renal cell carcinomas,
      and both benign and malignant angiomyolipomas. All of these occur in children as
      well as adults with TSC. Benign angiomyolipomas, which can cause spontaneous life
      threatening hemorrhage, are by far the most prevalent and the greatest source of
      morbidity. What is particularly unusual about TSC, setting it apart from
      virtually all other inherited forms of renal disease, is the abnormalities of
      both mesenchymal cells (angiomyolipomas) and epithelial cells (cysts,
      oncocytomas, and carcinomas). Recently, the TSC1/TSC2 protein complex was shown
      to inhibit the kinase mTOR (mammalian target of rapamycin). This places TSC1/TSC2
      at center stage in signaling pathways that regulate cell growth. Furthermore,
      recent advances in TSC1/TSC2 signaling open the door for targeted therapy for TSC
      patients. Here, we will address the genetic, cellular and biochemical mechanisms
      that may contribute to the unusually broad spectrum of renal disease in cells
      with TSC1 or TSC2 mutations, and consider how the TSC signaling pathways may be
      linked to other renal diseases such as polycystic kidney disease and renal cell
      carcinoma.

PMID- 15856329
TI  - Catastrophic antiphospholipid antibody syndrome.
AB  - Antiphospholipid antibody syndrome (APS) is characterized by recurrent thrombosis
      with the presence of circulating antiphospholipid antibodies. A diagnosis of APS
      requires the presence of at least one clinical and one laboratory criteria
      (detection of aCL IgG or IgM antibodies or the presence of lupus anticoagulant on
      two or more consecutive occasions 6 weeks apart). A severe, rapidly progressive
      form characterized by clinical involvement of at least three different organ
      systems with histopathological evidence of small and large vessel occlusion is
      termed catastrophic antiphospholipid syndrome. Early recognition of APS is
      crucial since aggressive management can result in a favorable outcome. We present
      the case of a 12-year-old boy who presented with a devastating illness with
      multiple thrombotic episodes and rapidly progressive renal failure.

PMID- 15856330
TI  - Effects of ambient temperature steps on thermal comfort requirements.
AB  - The purpose of this study was to determine the thermal comfort requirements for
      steps in temperature. Thirty male subjects were exposed for 50 min to a 34 or 37
      degrees C condition, and then quickly transferred to a cooler environment of 31,
      28, 25, and 22 degrees C for 50 min. Mean skin temperature was continuously
      measured, and the subjects reported their thermal sensation and comfort sensation
      every 2 min. Just after the step changes, the mean skin temperature immediately
      decreased, while the thermal sensation overshot and gradually rose again. Both
      the skin temperature and the thermal sensation seemed to reach a constant level
      within about 20 min. However, there were differences in the mean skin temperature
      and the neutral temperature derived from the correlation between the ambient
      temperature and the thermal sensation even 50 min after the steps, due to the
      thermal environmental condition before the changes of temperature. The change in
      the neutral temperature with time was expressed as two attenuating equations.
      These equations indicate that there is an obvious difference between the neutral
      temperatures due to the thermal condition before step changes, and that it takes
      >50 min after the step changes to reach the steady state. It is expected that
      these equations predict in quantitative terms the thermal comfort requirements
      within a given experimental condition.

PMID- 15856331
TI  - Spiritual needs in cancer patients and spiritual care based on logotherapy.
AB  - BACKGROUND: The suitability of Frankl's logotherapy for the spiritual care
      (psychotherapy) of cancer patients in Japan is suggested. Using Functional
      Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp, Japanese version), the
      Purpose in Life test (PIL test, Japanese version), and WHO-Subjective Inventory
      (WHO-SUBI, Japanese version), we attempted to elucidate the complicated structure
      of spirituality in cancer patients in order to identify possible approaches to
      their spiritual care and means of evaluating such care. MATERIALS: Two hundred
      and ninety-eight cancer patients participated in the study. All three tests were
      taken at the same time, and the results were evaluated by principal component
      analysis. RESULTS: It was demonstrated that all the subscales employed in the
      present study could be represented by a two-dimensional structure (two principal
      components), and that the FACIT-Sp and PIL tests have similar contents.
      DISCUSSION: FACIT-Sp (Japanese version) is very similar in conception to the PIL
      test, which was prepared in accordance with logotherapy. The results suggest that
      this test can serve as an adequate evaluation scale for measuring the
      effectiveness of spiritual care based on Frankl's logotherapy.

PMID- 15856332
TI  - Information needs of patients with incurable cancer.
AB  - GOALS: The aims of this study were to describe to what extent cancer patients
      with incurable cancer report to have been informed about disease-related topics
      and how they evaluate the quality of the information giving. PATIENTS AND
      METHODS: One hundred and twenty-eight patients participated in our study within 2
      months after having had a diagnosis of incurable cancer. They filled out a
      questionnaire and were interviewed personally. We assessed the level of
      information, information needs and demographic factors, and we registered the
      type and duration of the cancer, cancer therapy, other types of received care and
      contacts with health care professionals. Furthermore, we assessed patients'
      appreciation of the information giving by their health care professionals. MAIN
      RESULTS: The majority of the patients said to have been informed about treatment
      options, side effects of their treatment, physical symptoms, where to get help,
      helpful devices, and diet, whereas less than half of the patients were informed
      about psychosocial care, euthanasia, and complementary care. Of all patients, 39%
      felt a need for additional information about topics such as physical symptoms,
      diet, euthanasia, and alternative or complementary care, whereas 19% would have
      appreciated extra written information. Most patients (78-88%) were satisfied with
      the information giving by the clinical specialist, oncology nurses, and non
      specialised nurses, but only 63% evaluated the information giving by general
      practitioners as good. CONCLUSION: We conclude that most patients feel
      sufficiently informed about important disease-specific issues and are satisfied
      with the information giving by health care professionals. Nevertheless, a
      considerable number of patients appreciate additional information.

PMID- 15856333
TI  - An innovative rapid response radiotherapy program to reduce waiting time for
      palliative radiotherapy.
AB  - BACKGROUND: Waiting for radiation therapy (RT) in Ontario has been a major
      problem for the past decade. In 1996, the Toronto-Sunnybrook Regional Cancer
      Centre (TSRCC) initiated a Rapid Response Radiotherapy Program (RRRP) to provide
      timely palliative RT for symptom relief of patients with terminal cancer.
      PURPOSE: This study reviews the clinical activity of the RRRP over the past 8
      years to evaluate if we are meeting the objectives of the program. MATERIALS AND
      METHODS: From the TSRCC oncology patient information system (OPIS) database, we
      retrieved the number of patients referred to the RRRP, their demographics,
      diagnosis and treatment for the calendar years 1996 to 2003 inclusive. We
      calculated the time interval between referral to consultation, consultation to
      simulation and the percentage of cases who started RT on their initial
      consultation for all new cases referred to the RRRP. RESULTS: From 1996 to 2003,
      the number of cases seen in consultation increased from just over 200 cases
      annually in the first 2 years to about 500 cases per year in the last 4 years,
      for a total of 3,290. There were 1,792 (54%) men and 1,498 (46%) women; median
      age was 69 years (range, 21-95 years). Breast, lung, genitourinary and
      gastrointestinal primaries accounted for over 80% of all referrals. The majority
      was referred for palliative treatment of symptomatic bone (70%) or brain (14%)
      metastases. The dose fractionation for bone metastases was a single 8-Gy fraction
      in 45%, 20 Gy in five fractions in 42%, 30 Gy in ten fractions in 4% and other
      dose fractionations in 9%. Nearly 90% were seen within 2 weeks of referral (38%
      within 1 week). Eighty-five percent were simulated on the day of their initial
      consultation. Sixty percent started their RT treatment on the day of their
      consultation visit. The overall median interval from referral to treatment was 8
      days. CONCLUSION: Over the past 8 years, the annual number of new cases referred
      to the RRRP has doubled. The overall median interval from referral to
      consultation was 8 days. Sixty percent were simulated, planned and started
      treatment on the day of their initial consultation. We therefore are meeting our
      goal of providing rapid access to palliative RT for symptomatic cancer patients.

PMID- 15856334
TI  - The use of dietary supplements in a community hospital comprehensive cancer
      center: implications for conventional cancer care.
AB  - GOALS OF WORK: There is little data on the prevalence of use of dietary
      supplements in cancer, especially in light of the growing evidence that some
      dietary supplements can have adverse interactions with conventional cancer
      treatment. The purpose of this study was to investigate the use of dietary
      supplements among adult cancer patients in a community hospital comprehensive
      cancer center. PATIENTS AND METHODS: A survey of 227 new adult cancer patients
      presenting for treatment for the first time at Cancer Treatment Centers of
      America at Midwestern Regional Medical Center, between November 2001 and October
      2003. Patients completed the McCune Questionnaire, a validated instrument that
      captures information on the use of 56 dietary supplements in cancer, at admission
      to the hospital. RESULTS: Of the 227 patients, 73% used some form of dietary
      supplements during the 30 day period before the survey was conducted. Dietary
      supplement use was significantly higher (p = 0.04) in patients with colorectal
      (80%) and breast (75%) cancer as compared to patients with lung cancer (53%).
      Patients with stage II (86%) and III (76%) disease at diagnosis were more likely
      (p = 0.02) to use dietary supplements as compared to those with stage I (71%)
      disease at diagnosis, while those with stage IV (61%) disease at diagnosis were
      least likely to use them. Of the 80 patients who had received chemotherapy within
      the last 30 days, 71% had also used dietary supplements in that timeframe and 25%
      had consumed one or more herbal therapies that are suspected to have adverse
      interactions with chemotherapy. Of the 57 patients combining chemotherapy with
      dietary supplements, 52.6% did not consult a healthcare professional.
      CONCLUSIONS: In our study, twenty-five percent of patients receiving chemotherapy
      were concurrently using dietary supplements suspected to have adverse
      interactions with chemotherapy, usually relying on information sources other than
      healthcare professionals. Given the prevalence rates of these agents, healthcare
      providers should systematically inquire about them, and consider the potential
      for drug-dietary supplement interactions in treatment planning.

PMID- 15856335
TI  - Efficacy of progressive muscle relaxation training and guided imagery in reducing
      chemotherapy side effects in patients with breast cancer and in improving their
      quality of life.
AB  - GOALS: This study was designed to assess the effectiveness of progressive muscle
      relaxation training (PMRT) and guided imagery (GI) in reducing the anticipatory
      nausea and vomiting (ANV) and postchemotherapy nausea and vomiting (PNV) of
      patients with breast cancer and to measure their effects on the patients' quality
      of life (QoL). PATIENTS AND METHODS: Thirty chemotherapy-naive patients with
      breast cancer were randomized to the PMRT and GI group and 30 to the control
      group. Before each of six cycles of adjuvant chemotherapy, each patient was
      administered a self-report Multiple Affect Adjective Checklist (MAACL), and
      incidents of ANV and PNV for the first three postchemotherapy days were recorded.
      All patients were administered the Functional Assessment of Cancer Therapy-Breast
      (FACT-B) at baseline and after 3 and 6 months. RESULTS: We found that the PMRT
      and GI group was significantly less anxious, depressive, and hostile than the
      control group. We also found that the PMRT and GI group experienced significantly
      less ANV and PNV and that 6 months after CT, the QoL of the PMRT and GI group was
      higher than that of the control group. CONCLUSION: These results indicate that
      PMRT and GI were associated with both the improvements in ANV and PNV and in the
      QoL of patients with breast cancer.

PMID- 15856336
TI  - Successful inoculation of mature pine with Tricholoma matsutake.
AB  - Our finding demonstrates, for the first time, that the roots of mature pine trees
      can be successfully inoculated with a symbiotic ectomycorrhizal fungus, the
      valuable matsutake mushroom. Long root segments (ca. 5-10 mm in diameter, ca. 50
      cm in length) of 50-year-old Pinus densiflora trees were excavated, washed, auxin
      treated (2-5 mg indole butyric acid, IBA, per root) and incubated in moist
      Spagnum moss. Twelve months later, short roots were regenerated, of which
      approximately 90% were free of mycorrhizae. Mycorrhiza-free short roots were
      inoculated with mycelial pieces of Tricholoma matsutake and incubated further in
      a sterilized substrate. Four-and-a-half months later, roots putatively colonized
      by Matsutake were sampled near the inoculation points. A T. matsutake-specific
      ITS-rDNA fragment was amplified by nested PCR from approximately 80% of the root
      samples analyzed, whereas approximately 66% of the root samples processed for
      staining with Chlorazol black E displayed characteristic T. matsutake Hartig net
      structures. These results confirm the symbiotic infection of mature P. densiflora
      roots by matsutake.

PMID- 15856337
TI  - First detailed description of axial traction techniques by Serefeddin Sabuncuoglu
      in the 15th century.

PMID- 15856338
TI  - Evaluation of the kinesthetic sense and function of the hand in early period in
      operated cervical disc hernia.
AB  - A prospective study made into cervical disc hernias. To determine the kinesthetic
      sense and hand functions, which are important for the patients with cervical disc
      hernia to return to work life and daily activities that need skill. Neurosurgical
      department. Data Symptoms in cervical disc hernias and hand functions are
      affected depending on long-term pain. The evaluation of the hand is essential in
      assessing the patients' overall recovery and ability to return to daily
      activities and work life. Thirty-four patients with cervical disc hernia, who
      were operated on, were included in the study. Eight different test positions in
      the assessment of the hand's kinesthetic sense and hand function sort (HFS) in
      the evaluation of the hand function were applied. The disability levels of the
      patients were determined with The Neck Pain and Disability Scale, on the
      preoperative and postoperative discharge day and in the postoperative second
      month. Patients were divided into groups according to the side involved. In the
      evaluation of the kinesthetic test of the hand, only in the postoperative second
      month was a significant difference observed between the 1, 2, 3, and 4 test
      positions of the right side of the groups. On the other hand, no significant
      difference was found between the groups in the assessment of the hand function.
      In the measurement of hand functions and disability levels, strong and important
      correlations were determined. An early assessment of the hand's kinesthetic sense
      and function is instrumental in the patients' evaluation of recovery and
      resumption of work.

PMID- 15856339
TI  - Multilevel vertebral hemangiomas: two episodes of spinal cord compression at
      separate levels 10 years apart.
AB  - This case report presents a 66-year-old woman with multiple vertebral hemangiomas
      causing spinal cord compression at different levels with a long symptom-free
      interval between episodes of compression. She presented with back pain and
      progressive weakness and numbness in her lower limbs for 3 months. Ten years
      earlier, she had had a symptomatic T4 vertebral hemangioma operated successfully,
      and had made a full recovery. Magnetic resonance imaging (MRI) of the thoracic
      and lumbar spine revealed multiple thoracic and lumbar vertebral hemangiomas.
      Extraosseous extension of a hemangioma at T9 was causing spinal cord compression.
      Selective embolization was performed preoperatively, and cord decompression was
      achieved via anterior T9 corpectomy. The patient's neurological status improved
      rapidly after surgery. After a course of radiotherapy, she was neurologically
      intact and could walk independently. One year later, MRI showed complete
      resolution of the cord edema at T9, and showed regression of the high signal
      intensity that had been observed at unoperated levels. These findings indicated
      diminished vascularity and reduced aggression of the tumor.

PMID- 15856340
TI  - Development of a German version of the Oswestry Disability Index. Part 2:
      sensitivity to change after spinal surgery.
AB  - When functional scales are to be used as treatment outcome measures, it is
      essential to know how responsive they are to clinical change. This information is
      essential not only for clinical decision-making, but also for the determination
      of sample size in clinical trials. The present study examined the responsiveness
      of a German version of the Oswestry Disability Index version 2.1 (ODI) after
      surgical treatment for low back pain. Before spine surgery 63 patients completed
      a questionnaire booklet containing the ODI, along with a 0-10 pain visual
      analogue scale (VAS), the Roland Morris disability questionnaire, and Likert
      scales for disability, medication intake and pain frequency. Six months after
      surgery, 57 (90%) patients completed the same questionnaire booklet and also
      answered Likert-scale questions on the global result of surgery, and on
      improvements in pain and disability. Both the effect size for the ODI change
      score 6 months after surgery (0.87) and the area under the receiver operating
      characteristics (ROC) curve for the relative improvement in ODI score in relation
      to global outcome 6 months after surgery (0.90) indicated that the ODI showed
      good responsiveness. The ROC method revealed that a minimum reduction of the
      baseline (pre-surgery) ODI score by 18% (equal to a mean 8-point reduction in
      this patient group) represented the cut-off for indicating a "good" individual
      outcome 6 months after surgery (sensitivity 91.4% and specificity 82.4%). The
      German version of the ODI is a sensitive instrument for detecting clinical change
      after spinal surgery. Individual improvements after surgery of at least an 18%
      reduction on baseline values are associated with a good outcome. This figure can
      be used as a reliable guide for the determination of sample size in future
      clinical trials of spinal surgery.

PMID- 15856341
TI  - Development of a German version of the Oswestry Disability Index. Part 1: cross
      cultural adaptation, reliability, and validity.
AB  - Patient-orientated assessment methods are of paramount importance in the
      evaluation of treatment outcome. The Oswestry Disability Index (ODI) is one of
      the condition-specific questionnaires recommended for use with back pain
      patients. To date, no German version has been published in the peer-reviewed
      literature. A cross-cultural adaptation of the ODI for the German language was
      carried out, according to established guidelines. One hundred patients with
      chronic low-back pain (35 conservative, 65 surgical) completed a questionnaire
      booklet containing the newly translated ODI, along with a 0-10 pain visual
      analogue scale (VAS), the Roland Morris Disability Questionnaire, and Likert
      scales for disability, medication intake and pain frequency [to assess ODI's
      construct (convergent) validity]. Thirty-nine of these patients completed a
      second questionnaire within 2 weeks (to assess test-retest reliability). The
      intraclass correlation coefficient for the test-retest reliability of the
      questionnaire was 0.96. In test-retest, 74% of the individual questions were
      answered identically, and 21% just one grade higher or lower. The standard error
      of measurement (SEM) was 3.4, giving a "minimum detectable change" (MDC(95%)) for
      the ODI of approximately 9 points, i.e. the minimum change in an individual's
      score required to be considered "real change" (with 95% confidence) over and
      above measurement error. The ODI scores correlated with VAS pain intensity (r =
      0.78, P < 0.001) and Roland Morris scores (r = 0.80, P < 0.001). The mean
      baseline ODI scores differed significantly between the surgical and conservative
      patients (P < 0.001), and between the different categories of the Likert scales
      for disability, medication use and pain frequency (in each case P < 0.001). Our
      German version of the Oswestry questionnaire is reliable and valid, and shows
      psychometric characteristics as good as, if not better than, the original English
      version. It should represent a valuable tool for use in future patient-orientated
      outcome studies in German-speaking lands.

PMID- 15856342
TI  - The time-dependent transport of chromium in adult rats from the bloodstream to
      the urine.
AB  - While chromium was proposed to be an essential trace element over 40 years ago
      and if essential should possess a specific transport and distribution mechanism,
      the details of its transport from the bloodstream to the urine have not been
      elucidated. However, chromium is known to be maintained in the bloodstream bound
      to transferrin and to be excreted in the urine bound to the oligopeptide
      chromodulin or a similar chromodulin-like species. Injection of (51)Cr-labeled
      transferrin into the bloodstream resulted in a rapid and insulin-sensitive
      movement of chromium into the tissues as Cr transferrin; greater than 50% of the
      Cr is transported to the tissues within 30 min. Tissue levels of Cr are maximal
      30 min after injection; decreases in tissue Cr with time are mirrored by
      increases in urine Cr. Approximately 50% of the (51)Cr appears in the urine
      within 360 min of injection in the absence of added insulin; insulin treatment
      concurrent with injection of (51)Cr-labeled transferrin results in approximately
      80% of the label appearing in the urine within 180 min. The removal of (51)Cr
      from the blood is faster than the appearance of (51)Cr in the urine; the lag in
      time indicates that the Cr transferrin in the blood and Cr in the urine are not
      in direct equilibrium and that intermediates in the transport of Cr must be
      involved. This establishes a clear pathway of transport of Cr starting from
      transport by transferrin from the bloodstream into the tissues, followed by
      release and processing in the tissues to form chromodulin, excretion into the
      bloodstream, rapid clearance of chromodulin or a similar species into the urine,
      and ultimately excretion as this species. Insulin stimulates the processing of Cr
      in the tissues.

PMID- 15856344
TI  - The effect of dental profile on daily functions of the elderly.
AB  - The aim of the study was to evaluate statistically dentition and its effect on
      daily functions for a group of elderly volunteers. The study was conducted on 144
      elderly people (86 males, 58 females) living in different nursing homes in
      Ankara, Turkey. Their ages varied between 60 and 100 years. Data assessed as
      dentition variables were number of teeth remaining and prosthesis use. Nearly 55%
      of the residents were edentulous and removable prosthesis users. The mean number
      of remaining teeth in subjects aged 60-69 was highest for all age groups in both
      sexes. The level of education and dental insurance of these subjects were also
      correlated with the dentition of elderly subjects. We found a statistically
      significant increase in the number of removable prosthesis users among educated
      and insured subjects. Functional capacity was better when the subjects had more
      remaining teeth or a removable prostheses. It is revealed by this study that
      healthy and good dentition prevents the decline of daily function and improves
      the social interaction and general well being of the elderly.

PMID- 15856343
TI  - Bond strength of a new universal self-adhesive resin luting cement to dentin and
      enamel.
AB  - The objective of this study was to assess the bonding performance of a new
      universal self-adhesive cement RelyX Unicem (RXU) to dentin and enamel compared
      to four currently used luting systems, using a shear bond strength test with and
      without thermocycling. Median bond strengths were determined after 24 h storage,
      and after thermocycling (6,000 cycles, 5-55 degrees C) for RXU and compared to
      Syntac/Variolink II (SynC/V) as a standard for luting conventional ceramics, ED
      Primer II/Panavia F2.0 (EDII/PF2), Prime and Bond NT/Dyract Cem Plus (PBNT/DyCP),
      and a glass ionomer cement, Ketac Cem (KetC), as a standard for luting high
      strength ceramic and metal-based restorations. Data (n=10 per group) were
      statistically analyzed using the Mann-Whitney-Wilcoxon test at the 0.05 level of
      significance. The bond strength (MPa) of RXU to dentin (10.8) was not
      statistically different from those of SynC/V (15.1), EDII/PF2 (10.5) or PBNT/DyCP
      (10.1), and statistically higher than KetC (4.1). The bond strength of RXU to
      enamel (14.5) was significantly lower than those of SynC/V (32.8), EDII/PF2
      (23.6), and PBNT/DyCP (17.8), but higher than KetC (6.1). After thermocycling,
      the bond strength of RXU to enamel significantly decreased, but was still
      significantly higher than that of KetC. RelyX Unicem may be considered an
      alternative to Ketac Cem for high-strength ceramic or metal-based restorations,
      and may be used for luting conventional ceramic crowns with little or no enamel
      left.

PMID- 15856345
TI  - Quantification of oxidative metabolism in masseter muscle of denture wearers.
AB  - This study aimed to quantify oxidative metabolism in masseter muscle using near
      infrared spectroscopy, in particular for denture wearers. Fourteen normal dentate
      subjects without malocclusion (ND group, 25-50 years) participated in the
      quantification of oxidative metabolism. Eleven partially edentulous patients
      without occlusal stops (PD group, 64-80 years) and ten edentulous patients (CD
      group, 57-84 years) also participated after prosthodontic treatment. Oxidative
      metabolism was recorded during gum chewing, maximum clenching and regulated
      clenching at 5 kgf. The oxygenated hemoglobin at 5 kgf clenching level was
      normalized to the oxygenated hemoglobin at the lowest blood flow and expressed as
      oxygen consumption rate (OCR). The relationship of the OCR to the maximum
      clenching force was analyzed using Pearson's correlation coefficient, and
      differences between the PD and CD groups were tested by unpaired Student's t
      test. The OCR showed a significant negative correlation with maximum clenching
      force in the ND group. The OCR of the PD group was significantly greater than
      that of the CD group, although the difference in maximum clenching force was not
      significant between both groups. These results suggest that the aerobic ability
      of masseter muscle in complete denture wearers is relatively greater than in
      partial denture wearers with same age level.

PMID- 15856346
TI  - [Evaluation of potential damage to the regenerate during callus molding after
      mandibular distraction osteogenesis. Experimental study using an animal model].
AB  - BACKGROUND: Molding the regenerate created by distraction osteogenesis has
      clinically been shown to be an efficient lifeboat, good enough that for complex
      three-dimensional deformities final adjustments by molding the regenerate may be
      part of the treatment plan. The study assessed the limits of molding a
      regenerate, taking into consideration compressive and tensile forces acting
      simultaneously on the fresh callus. MATERIAL AND METHODS: Distraction
      osteogenesis was performed in 15 beagle mandibles using custom-made devices which
      allowed for lengthening as well as for angulation. After linear distraction of 10
      mm, a defined 20 degrees angulation was performed in one acute step. The position
      of the fulcrum of the device allowed the regenerate to be compressed and
      stretched simultaneously. The effects on bone healing were assessed after 6 or 13
      weeks of consolidation and compared to a control group where only linear
      distraction was performed. RESULTS: Radiological and histological investigations
      demonstrated that no significant difference between the biological behavior of
      the compressed and the stretched zone of the regenerate could be found. However,
      there were signs, showing the more critical character of the stretched area.
      After 6 weeks of consolidation, some specimens revealed delayed ossification of
      the stretched zone. Under stable conditions, this delay was compensated after 13
      weeks of consolidation and complete osseous healing occurred. CONCLUSIONS: Under
      stable conditions, a fresh regenerate can be molded to a considerable extent
      without endangering osseous healing permanently. Nevertheless, tensile forces
      acting on the regenerate should be minimized to prevent damage to the new bone.
      This can be achieved by overdistraction prior to callus molding or by gradually
      changing the vector of distraction during the lengthening process.

PMID- 15856347
TI  - Comparative analysis of expressed sequence tags from different organs of Vitis
      vinifera L.
AB  - Expressed sequence tags (ESTs) are providing a valuable approach to sampling
      organism-expressed genomes, especially when studying large genomes such as those
      of many plants. We report on the comparison of 8,647 ESTs generated from six
      different grape (Vitis vinifera L.) organs: berry, root, leaf, bud, shoot and
      inflorescence. Clustering and assembly of these ESTs resulted in 4,203 unique
      sequences and revealed that at this level of EST sampling, each organ shares a
      low percentage of transcripts with the others. To define organ relationships
      based on EST counts, we calculated a distance matrix of pairwise correlation
      coefficients between the libraries which indicated bud, inflorescence and shoot
      as a group distinct from the other organs considered in this study. A putative
      function was identified for about 85% of the unique sequences. By assigning them
      to specific functional classes, we were able to highlight strong differences
      between organs in the metabolism, protein biosynthesis and photosynthesis
      categories. This grape EST collection has also proven to be a valuable source for
      the development of 'functional' simple sequence repeats (SSRs) markers: a total
      of 405 SSRs have been identified. EST sequences and annotation results have been
      organised in the IASMA-grape database, freely available at the address
      http://genomics.iasma.it.

PMID- 15856348
TI  - The auxin-responsive GH3 gene family in rice (Oryza sativa).
AB  - Auxin regulates plant growth and development by altering the expression of
      diverse genes. Among these, the genes of Aux/IAA, SAUR, and GH3 classes have been
      extensively studied in dicots, but little information is available on monocots.
      We have identified 12 members of GH3 gene family in rice using sequences of full
      length cDNA clones available from KOME and analysis of the whole genome sequence
      of rice. The genomic organization as well as chromosomal location of all the
      OsGH3 genes is reported. The rice GH3 proteins can be classified in two groups
      (groups I and II) on the basis of their phylogenetic relationship with
      Arabidopsis GH3 proteins. Based upon the sequences available in the database, not
      a single group III GH3 protein could be identified in rice. An extensive survey
      of EST sequences of other monocots led to the conclusion that although GH3 gene
      family is highly conserved in both dicots and monocots but the group III is
      conspicuous by its absence in monocots. The in silico analysis has been
      complemented with experimental data to quantify transcript levels of all GH3 gene
      family members. Using real-time polymerase chain reaction, the organ-specific
      expression of individual OsGH3 genes in light- and dark-grown seedlings/plants
      has been examined. The transcript abundance of nearly all OsGH3 genes is enhanced
      on auxin treatment, with the effect more pronounced on OsGH3-1, -2, and -4. The
      functional validation of these genes in transgenics or analysis of gene-specific
      insertional mutants will help in elucidating their precise role in auxin signal
      transduction.

PMID- 15856349
TI  - Gene expression profiling of potato responses to cold, heat, and salt stress.
AB  - In order to identify genes involved in abiotic stress responses in potato,
      seedlings were grown under controlled conditions and subjected to cold (4 degrees
      C), heat (35 degrees C), or salt (100 mM NaCl) stress for up to 27 h. Using an
      approximately 12,000 clone potato cDNA microarray, expression profiles were
      captured at three time points following initiation of the stress (3, 9, and 27 h)
      from two different tissues, roots and leaves. A total of 3,314 clones could be
      identified as significantly up- or down-regulated in response to at least one
      stress condition. The genes represented by these clones encode transcription
      factors, signal transduction factors, and heat-shock proteins which have been
      associated with abiotic stress responses in Arabidopsis and rice, suggesting
      similar response pathways function in potato. These stress-regulated clones could
      be separated into either stress-specific or shared-response clones, suggesting
      the existence of general response pathways as well as more stress-specific
      pathways. In addition, we identified expression profiles which are indicative for
      the type of stress applied to the plants.

PMID- 15856350
TI  - A cross-national perspective on cost of illness: a comparison of studies from The
      Netherlands, Australia, Canada, Germany, United Kingdom, and Sweden.
AB  - All Western health systems are in search of efficiency. Cost of illness (COI)
      studies can contribute to the efficiency debate by elucidating the relation
      between health expenditure and health status and population demography. Since the
      purpose of COI data being summarized in the OECD Health Data publications is to
      facilitate cross-national comparisons, it is important to assess the
      comparability. We compared COI data from six countries at macrolevel of total
      health expenditure and disaggregated the data from four countries to sectors such
      as hospitals, drugs, health professionals, and residential care. Although the
      distribution of health expenditure over major diseases showed similar patterns in
      all countries, overall comparability was bad. We conclude that the current scope
      of COI studies is bound to national levels because health care systems dominate
      the magnitude and distribution of health expenditure. Cross-national comparisons
      may be possible if data and methods are standardized, and COI estimates are made
      for a common comparable package.

PMID- 15856351
TI  - Mold colonization during use of preservative-treated and untreated air filters,
      including HEPA filters from hospitals and commercial locations over an 8-year
      period (1996-2003).
AB  - High efficiency particulate arrestance (HEPA; 99.97% efficient at 0.3 microm)
      filters, filters with ASHRAE particulate arrestance rating of 90-95% at 1 mum (90
      95% filters), and lower efficiency cellulosic-polyester filters from air
      conditioning systems in hospitals and commercial buildings were removed from the
      systems and examined microscopically for mold colonization. Cellulosic-type
      filters from systems with water entrainment problems typically were colonized, or
      became colonized upon incubation in moisture chambers. Species of Acremonium,
      Aspergillus, and Cladosporium were most common. With air filters of all types,
      treatment of filter media with an antimicrobial preservative tended to reduce or
      delay colonization. Mold colonization of HEPA and 90-95% filters was observed
      most often on the load surfaces, but two untreated HEPA filters were permeated
      with fungi, one with Aspergillus flavus, the other with Cladosporium sp. Air
      filters in heating, ventilating, and air conditioning (HVAC) systems,
      particularly those with chronic or periodic exposure to moisture, may serve as
      point sources for indoor molds.

PMID- 15856352
TI  - Titration biosensors for the estimation of the biochemical nitrate demand of
      municipal and industrial wastes.
AB  - An anoxic titrimetric test was investigated for measuring denitrification
      potential of different wastewaters, both municipal and industrial, and to
      quantify the denitrifying activity in an activated sludge system. The method
      measures the amount of acid that is required to maintain the pH set-point value
      in a batch denitrification experiment, and it was performed using a DENICON
      (denitrification controller) biosensor. The amount of acid is proportional to the
      nitrate used to oxidise the biodegradable chemical oxygen demand present in the
      wastewater, while the acid consumption rate is used to derive the denitrifying
      activity. The wastewaters tested were a municipal wastewater (MW), an industrial
      municipal wastewater (MIW; 70% and 30%, respectively), and four industrial
      wastewaters drawn from an ice-cream factory (IW1), a beet-sugar factory (IW2), a
      brewery (IW3), and a tuna cannery industry (IW4). Good correlation between
      titration data and analyses was found.

PMID- 15856354
TI  - Comparison of wild-type and UV-mutant beta-glucanase-producing strains of
      Talaromyces emersonii with potential in brewing applications.
AB  - A screen of 46 UV-mutant strains of the moderately thermophilic fungus
      Talaromyces emersonii yielded two mutants (TC2, TC5) that displayed gross
      morphological differences to the parent strain and enhanced activity against
      mixed linkage cereal beta-glucans. Activity against beta-(1, 3)(1, 4)-D: -glucan
      from barley (BBGase) was measured during growth of the mutant and wild-type
      strains on a variety of carbon sources, ranging from solka floc to crude cereal
      fractions. In liquid culture, TC2 and TC5 secreted 1.2- to 8.6-fold more BBGase
      than the parent strain and markedly less beta-glucosidase (exo-activity); enzyme
      levels were dependent on the carbon source. Cellulose induced high BBGase.
      However, beet pulp, wheat bran, carob and tea-leaves were cheap and effective
      inducers. T. emersonii wild-type, TC2 and TC5 crude enzyme preparations achieved
      similar end-points during the hydrolysis of commercial barley beta-glucan (13.0
      16.9%), but were more active against crude beta-glucan from barley (16.0-24.2%
      hydrolysis). The products of hydrolysis were quantified by high-performance anion
      exchange chromatography. Mash trials indicated that enzyme preparations from all
      three organisms effected a significant reduction in wort viscosity and residual
      mash beta-glucan. Finally, TC2 and TC5 produce more efficient beta-glucan
      depolymerizing enzymes; and wheat bran and solka floc can be used to provide
      inexpensive and potent enzyme cocktails with potential in brewing applications.

PMID- 15856355
TI  - Transcriptional regulation and processing increase the functional variability of
      TRPM channels.
AB  - Mammalian TRP channels display heterogenous biophysical properties and are
      involved in a variety of signal transduction pathways. To carry out their diverse
      biological functions and to adapt these functions to changes of the environment,
      mechanisms to regulate their molecular structure are required. Transcriptional
      regulation and post-transcriptional RNA processing represent essential
      instruments to generate TRP channel variants with modified properties. TRP
      variants are expressed depending on the tissue and developmental state. They can
      show distinct biophysical properties and mechanisms of activation, and thereby
      determine channel function and malfunction in certain human diseases. In this
      review, we give an overview of the variants of a given TRP gene, with the focus
      on the TRPM subfamily, and discuss their relevance with respect to their function
      under physiological and pathological conditions.

PMID- 15856358
TI  - A multicenter, open, noncomparative, phase II study of the combination of
      cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating
      factor and mitoxantrone as induction therapy in refractory acute myeloid
      leukemia: a report of the Polish Adult Leukemia Group.
AB  - Purine nucleoside analogues, cladribine (2-chlorodeoxyadenosine, 2-CdA) and
      fludarabine (FAMP) are active agents in acute myeloid leukemias (AMLs).
      Synergistic interaction between FAMP or 2-CdA with cytarabine (cytosine
      arabinoside, Ara-C) has been demonstrated in preclinical and clinical studies.
      The current multicenter phase II study was initiated to evaluate the efficacy and
      toxicity of induction treatment consisting of 2-CdA (5 mg/m2), Ara-C (2 g/m2),
      mitoxantrone (MIT, 10 mg/m2) and granulocyte colony-stimulating factor (G-CSF)
      (CLAG-M) in refractory AML. In case of partial remission, a second CLAG-M was
      administered. Patients in complete remission (CR) received consolidation courses
      based on high-dose Ara-C and MIT with or without 2-CdA. Forty-three patients from
      five centers were registered: 25 primary resistant and 18 relapsed. CR was
      achieved in 21 (49%) patients, 20 (47%) were refractory and 2 (5%) died early.
      Hematologic toxicity was the most prominent toxicity of this regimen. The overall
      survival (OS; 1 year) for the 42 patients as a whole and the 20 patients in CR
      were 43% and 73%, respectively. Disease-free survival (1 year) was 68.6%. None of
      the analyzed prognostic factors influenced the CR and OS probability
      significantly. We conclude that CLAG-M regimen has significant antileukemia
      activity in refractory AML, which seems to be better than the activity of many
      other regimens. The toxicity of the treatment is acceptable.

PMID- 15856359
TI  - Proteomic response of the biological control fungus Trichoderma atroviride to
      growth on the cell walls of Rhizoctonia solani.
AB  - Trichoderma atroviride has a natural ability to parasitise phytopathogenic fungi
      such as Rhizoctonia solani and Botrytis cinerea, therefore providing an
      environmentally sound alternative to chemical fungicides in the management of
      these pathogens. Two-dimensional electrophoresis was used to display cellular
      protein patterns of T. atroviride (T. harzianum P1) grown on media containing
      either glucose or R. solani cell walls. Protein profiles were compared to
      identify T. atroviride proteins up-regulated in the presence of the R. solani
      cell walls. Twenty-four protein spots were identified using matrix-assisted laser
      desorption ionisation mass spectrometry, liquid chromatography mass spectrometry
      and N-terminal sequencing. Identified up-regulated proteins include known fungal
      cell wall-degrading enzymes such as N-acetyl-beta-D: -glucosaminidase and 42-kDa
      endochitinase. Three novel proteases of T. atroviride were identified, containing
      sequence similarity to vacuolar serine protease, vacuolar protease A and a
      trypsin-like protease from known fungal proteins. Eukaryotic initiation factor
      4a, superoxide dismutase and a hypothetical protein from Neurospora crassa were
      also up-regulated as a response to R. solani cell walls. Several cell wall
      degrading enzymes were identified from the T. atroviride culture supernatant,
      providing further evidence that a cellular response indicative of biological
      control had occurred.

PMID- 15856360
TI  - Interphase chromosomal abnormalities and mitotic missegregation of hypomethylated
      sequences in ICF syndrome cells.
AB  - The immunodeficiency, centromeric region instability, facial anomalies (ICF)
      syndrome is a rare autosomal recessive disease. Usually, it is caused by
      mutations in the DNA methyltransferase 3B gene, which result in decreased
      methylation of satellite DNA in the juxtacentromeric heterochromatin at 1qh,
      16qh, and 9qh. Satellite II-rich 1qh and 16qh display high frequencies of
      abnormalities in mitogen-stimulated ICF lymphocytes without these cells being
      prone to aneuploidy. Here we show that in lymphoblastoid cell lines from four ICF
      patients, there was increased colocalization of the hypomethylated 1qh and 16qh
      sequences in interphase, abnormal looping of pericentromeric DNA sequences at
      metaphase, formation of bridges at anaphase, chromosome 1 and 16 fragmentation at
      the telophase-interphase transition, and, in apoptotic cells, micronuclei with
      overrepresentation of chromosome 1 and 16 material. Another source of anaphase
      bridging in the ICF cells was random telomeric associations between chromosomes.
      Our results elucidate the mechanism of formation of ICF chromosome anomalies and
      suggest that 1qh-16qh associations in interphase can lead to disturbances of
      mitotic segregation, resulting in micronucleus formation and sometimes apoptosis.
      This can help explain why specific types of 1qh and 16qh rearrangements are not
      present at high frequencies in ICF lymphoid cells despite diverse 1qh and 16qh
      aberrations continuously being generated.

PMID- 15856361
TI  - Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men.
AB  - Both estrogens and androgens play important roles in skeletal development and
      maintenance in men. The relative importance of estrogens and androgens in male
      bone metabolism, however, remains undefined. Anastrozole is an oral aromatase
      inhibitor that decreases estrogen production and increases androgen production in
      men. Currently, anastrozole is being investigated as a potential agent for the
      treatment of hypogonadism in aging men. Because anastrozole lowers estrogen
      levels and raises androgen levels, its effect on bone metabolism is difficult to
      predict. To assess the effects of anastrozole on bone turnover, we randomized 37
      elderly (ages 62-74) mildly hypogonadal men (serum testosterone <350 ng/dl) to
      receive either anastrozole 1 mg daily (n=12), anastrozole 1 mg twice weekly
      (n=11), or daily placebo (n=14) for 12 weeks. Serum gonadal steroid levels, serum
      and urine biochemical markers of bone turnover, serum osteoprotegerin, and total
      body bone mineral density were measured at baseline and week 12. Mean serum
      levels of total and bioavailable testosterone increased substantially in both
      treated groups. Specifically, mean +/- SD bioavailable testosterone levels
      increased from 99+/-31 ng/dl to 207+/-65 ng/dl in the group receiving 1 mg of
      anastrozole daily and from 115+/-37 ng/dl to 178+/-55 ng/dl in the subjects
      receiving 1 mg of anastrozole twice weekly ( p <0.001 vs placebo for both
      groups). Serum estradiol levels decreased modestly in both treated groups (from
      26+/-8 pg/ml to 17+/-6 pg/ml in the daily treatment group and from 27+/-8 pg/ml
      to 17+/-5 pg/ml in the twice-weekly treatment group, p <0.001 vs placebo for both
      groups). Despite these hormonal changes, no increases in biochemical markers of
      bone resorption were observed. Specifically, mean serum N-telopeptide and urinary
      deoxypyridinoline concentrations remained stable in both treated groups over the
      12-week treatment period. Similarly, serum biochemical markers of bone formation
      (osteocalcin and amino-terminal propeptide of type 1 collagen), serum
      osteoprotegerin, and total body bone mineral density did not change. These data
      demonstrate that although short-term administration of anastrozole decreases
      serum estradiol levels in elderly men with mild hypogonadism, this intervention
      does not adversely affect bone metabolism over a 12-week period. This lack of an
      effect may be due to the concomitant increase in testosterone production, the
      relative modest effect on estradiol production, or a combination of both factors.
      These results suggest that anastrozole therapy is unlikely to have an adverse
      effect on bone metabolism when taken over extended periods and may prove to be a
      valuable method of normalizing testosterone production in older men.

PMID- 15856363
TI  - Light chain multiple myeloma in a patient with long-standing rheumatoid
      arthritis.

PMID- 15856362
TI  - The effect of vitamin K2 on bone metabolism in aged female rats.
AB  - Reactive oxygen species (ROS) may contribute to aging and osteoporosis resulting
      from marked decreases in plasma antioxidants in aged osteoporotic women. On the
      other hand, high-dose vitamin K2 (menaquinone-4: menatrenone, MK-4)
      supplementation has been reported to reduce ovariectomy-induced bone loss in rats
      and to decrease osteoporotic fracture in postmenopausal women. However, the
      mechanism by which vitamin K2 prevents osteoporosis is unclear. Recently, vitamin
      K2 has been suggested to preserve antioxidant activity as a novel function.
      Therefore, we investigated the effect of vitamin K2 on the osteoporosis of aged
      rats by evaluating the relationships between serum antioxidant levels and bone
      metabolism. Aged female rats exhibited significantly lower serum alkaline
      phosphatase activity and osteocalcin level, together with lower serum levels of
      antioxidants such as 17beta-estradiol, macrophage migration inhibitory factor
      (MIF) and glutathione peroxidase (GPx) activity, as compared with young female
      rats. On the other hand, vitamin K2 supplementation (500 mg/kg, food intake) for
      98 days led to a significantly increased serum vitamin K2 level (3,045+/-915
      ng/ml in the vitamin K2 supplemented group vs. 4.6+/-3.4 ng/ml in the control
      diet group; P<0.0001) with increased serum alkaline phosphatase activity and MIF
      level (P<0.05). Unexpectedly, however, it failed to increase the serum level of
      antioxidants such as GPx. Nor did it affect bone metabolism markers such as
      osteocalcin and osteopontin, which were significantly lower than in the young
      female rats (P<0.05). Finally, the histomorphometric properties of the proximal
      tibia in the femur were not altered by vitamin K2. These results suggest that
      high-dose vitamin K2 supplementation neither improves lowered antioxidant levels
      nor stimulates bone formation in aged rats.

PMID- 15856364
TI  - Osteogenesis imperfecta: a case with hand deformities.
AB  - In a 51-year-old woman with a history of fractures and dislocations after low
      intensity trauma in childhood, intensive blue sclera, short stature, and hearing
      loss, the diagnosis of osteogenesis imperfecta (OI) was suspected. She was
      referred to our clinic with hand deformities and left knee pain and stiffness.
      She had difficulty in walking and reported a history of immobilization for 6
      months because of knee pain. She had bilateral flexion contracture of the elbows
      which occurred following dislocations of the elbows in childhood. She had Z
      deformity of the first phalanges, reducible swan-neck deformity of the third
      finger of the left and the second finger of the right hand, flexion contracture
      of the proximal interphalangeal joint of the fifth finger of the left hand, and
      syndactyly of the third and fourth fingers of the right hand. Flexion
      contractures of both knees were observed. Pes planus and short toes were the
      deformities of the feet. Acute phase reactants of the patient were normal. She
      had no history of arthritis or morning stiffness. Bone mineral density evaluated
      by dual-energy X-ray absorptiometry (DEXA) showed severe osteoporosis of the
      femur and lumbar vertebrae. She had radiographic evidence of healed fractures of
      the left fibula, the third metacarpal, and the fourth and fifth middle phalanges
      of the right hand. OI, affecting the type I collagen tissue of the sclera, skin,
      ligaments, and skeleton, presenting with ligament laxity resulting in
      subluxations and hand deformities may be misdiagnosed as hand deformities of
      rheumatoid arthritis.

PMID- 15856365
TI  - West Nile virus meningitis in a chronic immunosuppressed patient with rheumatoid
      arthritis.
AB  - The clinical presentation of West Nile virus (WNV) can be severe in
      immunosuppressed patients. A 65-year-old with steroid-dependent rheumatoid
      arthritis on infliximab and methotrexate presented with meningitis and profound
      muscular weakness. Serum WNV IgM and IgG antibody were positive. WNV should be
      included in the differential diagnosis of neurological symptoms in peak months.

PMID- 15856366
TI  - High frequency of unusual gastric/duodenal ulcers in patients with Behcet's
      disease in Taiwan: a possible correlation of MHC molecules with the development
      of gastric/duodenal ulcers.
AB  - The gastrointestinal (GI) involvement of Behcet's disease (BD) mainly affects the
      ileocecal region and colon. The gastroduodenal mucosa appears to be the least
      frequently involved segment of the gastrointestinal tract. The objective of this
      study was to assess the severity of gastric/duodenal involvement in BD patients
      in Taiwan. Behcet's disease was diagnosed according to the diagnostic criteria
      issued by the International Study Group for Behcet's Disease. We obtained and
      recorded clinical and laboratory data. A routine endoscopic examination with a
      urease test for Helicobacter pylori infection was arranged. Furthermore, HLA
      tissue typing was also performed by polymerase chain reaction with sequence
      specific primers to evaluate the possible genetic loads associated with ulcer
      development. A total 28 BD patients, diagnosed at DaLin TzuChi hospital from 1999
      to 2002, were enrolled in this study. The prevalence rate of gastric/duodenal
      ulceration was 43% (six patients had combined gastric and duodenal ulcers, three
      patients had simple gastric ulcers, and three patients had simple duodenal
      ulcers). No risk factors of nonsteroidal anti-inflammatory drug (NSAID) or H.
      pylori infection were found to be associated with gastrointestinal ulcers in our
      BD patients. All patients with peptic ulcers responded well to systemic steroids
      and immunosuppressant treatment in this preliminary observation. Furthermore, 7
      of 12 gastric/duodenal ulcer patients (58%) carried an A2/B46/Cw1 or A11/B46/Cw1
      genotype. Our data indicated that gastric/duodenal ulcers were a common
      manifestation in Chinese patients with BD in Taiwan in close association with the
      distinct genotypes of A2/B46/Cw1 or A11/B46/Cw1. A good response to systemic
      steroids, rather than conventional H2 blockers, might be due to downregulation of
      the vasculitis.

PMID- 15856367
TI  - Quality of life in patients with fibromyalgia syndrome and rheumatoid arthritis.
AB  - The objective of this study was to determine and compare the quality of life
      (QOL) of patients with fibromyalgia syndrome (FS) and rheumatoid arthritis (RA)
      and to assess patients' psychological and functional status in each group. This
      prospective study included 62 female FS patients and 60 female RA patients
      diagnosed by the American College of Rheumatology criteria. The Turkish
      translations of the Arthritis Impact Measurement Scale II (AIMS II) and Beck
      Depression Index (BDI) were given to all of the patients and they were asked to
      complete the two questionnaires. The scores of AIMS II, pain, and QOL were
      evaluated in the FS and RA groups. There were no statistically significant
      differences between the FS and RA groups (p>0.05) in terms of QOL. The affect
      subgroup scores of the AIMS II and BDI were highly correlated in the FS and RA
      groups (p<0.002, r=0.85 and p<0.05, r=0.80, respectively). The results show that
      the QOL is negatively but similarly affected in FS and RA groups.

PMID- 15856368
TI  - Prolonged remission in adult-onset Still's disease with etanercept.

PMID- 15856369
TI  - Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome:
      ultrasonography as a diagnostic tool.
AB  - Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome
      is characterized by symmetrical synovitis and swelling of both the upper and
      lower extremities. The anatomical determinant of RS3PE is predominantly extensor
      tenosynovitis as revealed by magnetic resonance imaging (MRI). Given the cost
      constraints, time, and expertise required in carrying out MRI and ease in
      diagnosing tenosynovitis by ultrasound, we utilized high-frequency
      ultrasonography (USG) for evidence of tenosynovitis of the distal tendons in
      patients with RS3PE. Diagnosis of tenosynovitis was made on the basis of anechoic
      or hypoechoic signals around the tendon sheaths in both transverse and
      longitudinal planes. Flexor and extensor tendons at the wrist and metacarpal
      heads and extensor digitorum longus (EDL) tendons at the ankle were evaluated
      with a 7.5-10-MHz linear probe. There were ten patients (seven males) with a mean
      age of 59.5 years (range: 52-78 years) and mean disease duration of 6.1 months
      (range: 1.5-12 months). Disease onset was acute in all of the cases. Pitting
      edema of the hands was present in all except two patients whereas four patients,
      in addition, had edema of the feet. Edema was symmetrical in seven patients.
      Inability to make a complete fist was noted in all. Tenosynovitis of extensor and
      flexor tendons at the wrist and the metacarpal heads was documented in all
      patients with edema of the hands. In seven cases extensor tendon tenosynovitis
      was more prominent compared to the flexor tendons. Tenosynovitis of EDL tendons
      was detected in six cases. Dramatic relief with low-dose prednisolone was noted
      in all patients within 6 weeks of therapy. At a mean follow-up of 10.1 months all
      patients had marked relief in edema of extremities and improvement in the grip
      strength. Our study confirms that tenosynovitis of both flexor and extensor
      tendons at the wrist and extensor tendons of the feet is the hallmark of RS3PE
      syndrome. USG is a reliable and cost-effective modality for evaluation of
      patients with suspected RS3PE.

PMID- 15856371
TI  - Alarming trend of clarithromycin-resistant Streptococcus pyogenes in Japan (1998
      2002).
AB  - We investigated annual changes in clarithromycin resistance and resistance genes
      in 579 strains of Streptococcus pyogenes isolated from patients with symptomatic
      respiratory tract infections who visited primary medical institutions during the
      5-year period from 1998 to 2002. The minimum inhibitory concentrations (MICs) of
      clarithromycin for S. pyogenes were measured using the standard broth
      microdilution method according to the National Committee for Clinical Laboratory
      Standards (NCCLS) guidelines, and strains showing MICs of 1 microg/ml or greater
      were regarded as being resistant to clarithromycin, according to the resistance
      standard specified by the NCCLS. The rates of S. pyogenes resistance to
      clarithromycin were 7.3% overall, 5.8% in 1998, 4.9% in 1999, 7.7% in 2000, 6.4%
      in 2001, and 11.1% in 2002. While the annual rates fluctuated slightly each year,
      an overall tendency to increase was observed during the 5-year period. Regarding
      the macrolide-resistance genes in the macrolide-resistant strains, mefA/E (+)/
      ermB(-) was the most common genotype detected in these strains, while the ermB
      (+)/ mefA/E (-) and mef A/E (-)/ ermB (-) genotypes were detected at about the
      same rate. The MICs of clarithromycin for the ermB (+) strains tended to be
      higher than those of the mefA/E (+) strains, but some mefA/E (-) / ermB (-)
      strains also exhibited high MICs of clarithromycin, similar to those of the ermB
      (+) strains. The above results indicate that the number of clarithromycin
      resistant strains of S. pyogenes is gradually increasing and that the resistance
      is becoming stronger; thus, special attention must be paid to the appearance of
      macrolide-resistant strains of S. pyogenes.

PMID- 15856372
TI  - In vitro induction of resistance to metronidazole, and analysis of mutations in
      rdxA and frxA genes from Helicobacter pylori isolates.
AB  - In clinical Helicobacter pylori isolates, metronidazole resistance has been
      associated with mutations in the rdxA and frxA genes. The aim of this study was
      to examine the role of the rdxA and frxA genes after the in vitro induction of
      metronidazole resistance. A total of five suscep-tible H. pylori isolates were
      initially exposed to different subinhibitory metronidazole concentrations to
      induce in vitro resistance to metronidazole. Susceptible and resistant strains
      after the in vitro induction of resistance were examined to evaluate mutations of
      the rdxA and frxA genes by sequence analysis. After the in vitro induction of
      resistance, analysis revealed that two and four susceptible strains developed
      resistance when cultured with 0.3 microg/ml and 0.6 microg/ml of metronidazole,
      respectively. Before and after the induction of resistance, none of the
      susceptible strains that developed low and moderate levels of resistance
      presented any mutation in either of the evaluated genes, whereas strains with
      high-level metronidazole resistance contained a simple mutation of the frxA gene,
      but no specific changes in the rdxA gene. Strains with moderate-level resistance
      contained both single and multiple mutations of rdxA and frxA, respectively, and
      the low-level-metronidazole-resistant strain contained a single mutation in the
      frxA gene, without any significant change in the rdxA gene. In this study, the
      strains that developed resistance were mainly associated with mutations of the
      frxA gene, suggesting the possibility that inactivation of this gene could
      originate metronidazole resistance. The results after the in vitro induction of
      resistance to metronidazole suggested the presence of additional metronidazole
      resistance mechanisms, other than mutations of the rdxA and/or frxA genes.

PMID- 15856373
TI  - An epidemiological study of the susceptibility and frequency of multiple-drug
      resistant strains of Pseudomonas aeruginosa isolated at medical institutes
      nationwide in Japan.
AB  - The susceptibility of 3233 strains of Pseudomonas aeruginosa, isolated primarily
      in 2001, as agents of infection at 37 medical institutes with various specialties
      in seven regions of Japan (ranging from Hokkaido to Kyushu/Okinawa), to 18
      antipseudomonal agents known to be active against P. aeruginosa was evaluated, in
      accordance with the National Committee for Clinical Laboratory Standards (NCCLS)
      guidelines. Of the 18 antipseudomonal agents, including some combinations of beta
      lactamase inhibitors and antibacterial agents, ciprofloxacin had the lowest
      minimum inhibitory concentration (MIC)(50) (0.25 microg/ml) against P.
      aeruginosa, followed by meropenem, with an MIC(50) of 0.5 microg/ml. The MIC(50)
      of 7 of the examined antibacterial agents (ceftazidime, cefozopran, imipenem,
      biapenem, gentamicin, tobramycin, and levofloxacin) was between 1 and 2
      microg/ml. Among the antipseudomonal agents tested, tobramycin showed the lowest
      MIC(90) (2 microg/ml), which was not significantly different from its MIC(50) (1
      microg/ml). The MIC(90) of the other antibacterial agents examined ranged from 8
      to 64 microg/ml and more. The susceptibility of the 3233 strains to the 12
      antibacterial agents covered by the NCCLS guidelines was determined according to
      the standard method of the NCCLS guidelines. The frequency of strains resistant
      to meropenem, gentamicin, or tobramycin was relatively low (7.5%-8.3%). The
      frequency of strains showing intermediate to severe resistance to tobramycin was
      particularly low (8.0%). The frequency of strains resistant to aztreonam,
      imipenem, or levofloxacin was 16.7%-19.0%, about twice as high as the frequency
      of strains resistant to tobramycin. The susceptibility pattern of the 3233
      strains (isolated from seven regions of Japan) to five antibacterial agents
      (ceftazidime, piperacillin, imipenem, gentamicin, and ciprofloxacin) was
      evaluated in relation to the regions from which they were isolated. The MIC(50)
      values of these antibacterial agents did not differ significantly among the
      regions. However, the MIC(90) values of ceftazidime and gentamicin were higher
      for strains isolated from the Kansai region than for strains isolated from other
      regions. The MIC(90) of ciprofloxacin was higher for strains isolated from the
      Tohoku, Kansai, and Kyushu/Okinawa regions than for strains isolated from other
      regions. Of the 3233 strains, 89 were classified as multiple-drug-resistant
      (imipenem, gentamicin, and ciprofloxacin) strains. Of these 89 strains, 42 were
      isolated from urine, 17 from sputum or pharyngeal mucus, 13 from pus, 8 from
      blood, 1 from cerebrospinal fluid, and 8 from other specimens. The frequency of
      multiple-drug-resistant strains was higher among strains isolated from the Tohoku
      and Kansai regions than in strains isolated from other regions.

PMID- 15856374
TI  - Prediction of smallpox outbreak and evaluation of control-measure policy in
      Japan, using a mathematical model.
AB  - Since the September 1 terrorist attacks and moreover, since the anthrax exposure
      events in 2001 in the United States, bioterrorism attacks seem to be a real
      threat. Of course, the public health authorities in Japan have started to prepare
      control measures for such events. We report here our attempts, using a
      mathematical model, to estimate outbreak size and to examine the most effective
      measures; comparing ring vaccination (contact tracing, isolation, and vaccination
      among contacts) and mass vaccination of the susceptible population in the area.
      The basic framework of the mathematical model follows a model used in previous
      research. The initial susceptible population is assumed to be 30 million persons.
      Concerning the important parameters, such as the number of initial-exposure
      cases, R0 (infectious power, or natural history) and, the starting day of
      intervention after the initial exposure, we checked the robustness of our
      conclusions by sensitivity analysis. We found that mass vaccination is preferable
      to ring vaccination when the values for the initial-exposure cases and R0 are
      high and when the start of intervention by public health authorities is delayed.
      In the base-case situation, the mass vaccination strategy needs almost 30 million
      vaccine doses. On the other hand, though ring vaccination needs fewer doses, it
      needs fewer than 50,000 doses in the worst-case scenario, that with larger first
      exposure, higher R0, or later start of public health authority intervention. This
      mathematical model can measure the prevalence of an infectious disease and can
      evaluate control measures for it before an outbreak. Especially, it is useful for
      the planning of the outbreaks of emerging diseases such as severe acute
      respiratory syndrome (SARS) or for bioterrorism attacks involving such diseases
      as smallpox. In further research, we will have to take into account the
      population people vaccinated of for smallpox, who account for about 70% of the
      total population in Japan.

PMID- 15856375
TI  - Clinical utility of lipoarabinomannan antibody in pleural fluid for the diagnosis
      of tuberculous pleurisy.
AB  - We studied the clinical utility of the detection of lipoarabinomannan antibody,
      using MycoDot, in pleural fluid for the diagnosis of tuberculous pleurisy. Nine
      patients with active tuberculous pleurisy, 1 patient with chronic tuberculous
      empyema, and 16 patients with nontuberculous pleural effusions were studied. The
      results were positive in 5 patients with tuberculous pleural disease. Sensitivity
      was 50% (5 of 10; including the 1 patient with chronic tuberculous empyema) and
      specificity was 93.8% (15 of 16). Detection of lipoarabinomannan antibody using
      MycoDot in pleural fluid is a specific diagnostic tool for tuberculous pleurisy;
      furthermore, this diagnostic method is simple, rapid, and cost-effective.

PMID- 15856376
TI  - Compliance with an infectious disease specialist's advisory consultations on
      targeted antibiotic usage.
AB  - This study was conducted to evaluate the appropriateness of the use of targeted
      antibiotics, and to analyze compliance and the short-term impact of targeted
      antibiotic advisory consultations, as implemented in our hospital in October
      2002. Targeted antibiotics included glycopeptides, carbapenems, antipseudomonal
      cephalosporins, and aminoglycosides. A total of 339 prescriptions were reviewed
      from October 2002 through March 2003. Antimicrobial utilization density (AUD),
      which was the defined daily dose divided by 1000 patient days, was compared
      quarterly. Overall, 85.6% of the prescriptions were inappropriate, with 73.7%
      being inappropriate for therapeutic use and 100% inappropriate for prophylactic
      use. The overall compliance rate of attending physicians with the antibiotic
      advisory consultations was 46.5%. Compliance was higher in medical services than
      in surgical services (64.2% vs 43.1%; P = 0.005) and for therapeutic use than for
      prophylactic use (54.7% vs 36.5%; P = 0.001). The use of all parenteral
      antibiotics in the hospital decreased, from 770.8 AUD during the first quarter in
      2002 to 626.8 AUD during the second quarter in 2003 (P < 0.01). In conclusion,
      inappropriate antibiotic use for treatment and prophylaxis is common in our
      hospital. A targeted antibiotic advisory consultation may be an alternative means
      of ensuring more appropriate antibiotic use. However, more efficient antibiotic
      control measures should be developed and implemented, and prospective and
      continuous monitoring of antibiotic use is required.

PMID- 15856377
TI  - Isolation of nontuberculous mycobacteria from patients with pneumoconiosis.
AB  - This study aimed to confirm the isolation of nontuberculous mycobacteria (NTM)
      from patients with pneumoconiosis. Monthly sputum examinations in 155 patients
      were performed from April 1998 to December 2002. When NTM were isolated, species
      were identified and the frequency of isolation was reviewed. We then identified
      the patients who satisfied the bacteriologic criteria for the diagnosis of
      nontuberculous mycobacterial pulmonary disease (NTM pulmonary disease)
      recommended by the American Thoracic Society (ATS). Symptoms and findings on
      computed tomography (CT) scans were evaluated. NTM were isolated from 60 patients
      (39%): common etiologic species defined by the ATS, i.e., Mycobacterium avium, M.
      intracellulare, M. abscessus, and M. kansasii, were identified in 21 patients;
      unusual etiologic species, i.e., M. fortuitum, M. simiae, and M. szulgai, were
      identified in 11 patients; and undefined species, which appeared to be
      nonpathogenic, were identified in 41 patients. The bacteriologic criteria were
      satisfied in 8 patients. NTM species isolated in conformity with the
      bacteriologic criteria were: M. avium in 4 patients, M. intracellulare in 2, a
      combination of M. intracellulare and M. kansasii in 1, and M. gordonae in 1
      patient. Two patients, from whom M. avium were repeatedly isolated, satisfied the
      ATS diagnostic criteria for NTM pulmonary disease. It is important to note that
      NTM, including both pathogenic species and nonpathogenic species, were isolated
      from patients with pneumoconiosis.

PMID- 15856378
TI  - Escherichia coli O157 infection mimicking acute appendicitis: usefulness of
      computed tomography for differential diagnosis.
AB  - A 19-year-old man was admitted to our hospital with acute abdominal pain in the
      right lower quadrant. He had had mild diarrhea, of 1 day's duration, 2 days
      before admission. Although physical findings were consistent with a diagnosis of
      acute appendicitis, computed tomography findings showed marked wall thickening
      from the ascending colon to the cecum, findings which were similar to those in
      patients with hemorrhagic colitis due to Escherichia coli O157. Instead of
      emergency laparotomy, the patient was treated with antimicrobial agents, which
      led to rapid recovery. Diagnosis of intestinal infection due to E. coli O157 was
      established later, as serum antibody against lipopolysaccharide of E. coli O157
      was positive. E. coli O157 infection should be included in the differential
      diagnosis of diseases that exhibit marked wall thickening of the right colon on
      CT in patients with acute abdominal pain in the right lower quadrant who have
      mild transient diarrhea.

PMID- 15856379
TI  - Measles encephalitis in early pregnancy and after delivery.
AB  - We present two cases of measles encephalitis, one in early pregnancy and one
      after delivery. In case 1, the patient became unconscious 6 days after the
      appearance of a rash and was treated with glycerol and immunoglobulin. In case 2,
      the patient became unconscious 6 days after the appearance of a rash and was also
      treated with glycerol and immunoglobulin. Both of them recovered without any
      neurological sequelae. Pregnancy is a risk factor for severe measles
      complications, and vaccination should be promoted much more in countries with
      poor measles control, such as Japan.

PMID- 15856380
TI  - In vitro susceptibility of clinical isolates of Brucella melitensis to fucidic
      acid.
AB  - Brucella species are facultative intracellular bacteria, and therefore a limited
      number of antibiotics are effective against these organisms. The side effects of
      drug combination schemes, and the incidences of relapses and therapeutic
      failures, have led to investigations of new drugs to treat brucellosis. The
      purpose of this study was to test the in vitro susceptibility of 50 Brucella
      melitensis isolates to fucidic acid, which has not previously been used for the
      treatment of brucellosis. The minimum inhibitory concentrations (MICs) of fucidic
      acid to 50 B. melitensis isolates that were obtained from blood and bone marrow
      cultures of patients with brucellosis were studied by the broth microdilution
      method. The MIC50 and MIC90 values for the 50 B. melitensis strains'
      susceptibility to fucidic acid were determined to be 0.5 and 2 microg/ml,
      respectively, and the MIC range was 0.125-2.0 microg/ml. Further experiments are
      needed to reassess the activity of fucidic acid against intracellular Brucella
      spp.

PMID- 15856381
TI  - Investigation of beta-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR).
AB  - We could not detect hetero-vancomycin-intermediate resistant Staphylococcus
      aureus (hetero-VISA), according to the definition of hetero-VISA, from the
      clinical isolates of 140 methicillin-resistant S. aureus (MRSA) strains. However,
      15 beta-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR) strains were
      detected from the same strains. We screened 1882 MRSA clinical isolates obtained
      in 2002 from 21 institutes throughout Japan. The detection rate of blood-isolated
      BIVR was 12.6% (19/151), and that of nonblood-isolated BIVR was 4.9% (85/1731; P
      < 0.001; chi2 test). Uridine-diphosphate-N-acetylmuramyl-L: -alanyl-D: 
      isoglutamyl-L: -lysine, used as the peptidoglycan material of S. aureus, showed
      the same results as beta-lactam antibiotics in BIVR.

PMID- 15856382
TI  - Comparison of activities of beta-lactam antibiotics against Streptococcus
      pneumoniae with recombinant penicillin-binding protein genes from a penicillin
      resistant strain.
AB  - We investigated the antibacterial activities of 19 beta-lactams against three
      recombinant bacterial strains, in which three penicillin-binding protein genes,
      pbp2x, pbp1a, and pbp2b, from penicillin-resistant Streptococcus pneumoniae
      (PRSP), were transformed to a penicillin-susceptible strain. By the acquisition
      of the pbp2x gene from PRSP, the minimum inhibitory concentrations (MICs) of
      third-generation cephalosporins were increased more than eight fold. When the
      strain acquired the PRSP pbp1a gene in addition to pbp2x, the MICs of all tested
      beta-lactams increased 2- to 16-fold. When the strain acquired the PRSP pbp2b
      gene in addition to pbp2x and pbp1a, the MICs of penicillins and carbapenems
      increased 4- to 16-fold. However, two novel carbapenems, ME1036 and L-036, showed
      excellent antibacterial activities against these recombinant strains, as well as
      against the parent PRSP.

PMID- 15856383
TI  - Macrolide resistance of Streptococcus pneumoniae isolated during long-term
      macrolide therapy: difference between erythromycin and clarithromycin.
AB  - Longterm macrolide therapy (LTMT) has been employed as an effective therapy both
      for diffuse panbronchiolitis in Japan and for cystic fibrosis in European
      countries. However, effects on antibiotic susceptibility profiles of
      microorganisms, associated with such long-term administration of antibiotics, are
      of concern. We retrospectively identified 57 pneumococcal isolates, recovered
      from the same number of patients receiving either LTMT with 400 mg of
      clarithromycin daily (CAM group; n = 31) or 600 mg of erythromycin daily (EM
      group; n = 26) by reviewing the patients' records at Nara Medical University. On
      analysis, we found that all isolates recovered from the CAM group and 25 of the
      26 recovered from the EM group were resistant to EM, showing either an MLSB: or
      an M phenotype. Interestingly, isolates exhibiting the M phenotype were much less
      frequent in the CAM group (2 of 31; 6.5%) than in the EM group (15 of 26; 57.7%).
      No increase in the rate of penicillin resistance was observed in either group.
      The macrolide resistance profiles of microorganisms may be influenced differently
      according to differences in the kind of macrolide antibiotics used.

PMID- 15856385
TI  - [Pharmacogenetics in future medical care -- implications for patients and
      physicians].
AB  - PURPOSE: Since public acceptance of pharmacogenetic testing will largely
      influence their implementation in routine medical care, common implications of
      pharmacogenetic testing from patients', physicians' and scientists' perspective
      are reviewed. METHODS: Broad literature review (MEDLINE; MeSH terms:
      Pharmacogenetics, Delivery of Health Care, Ethics, Attitude, Patient Acceptance
      of Health Care) of empirical and theoretical studies describing psychological,
      family-related, social, and ethical consequences of pharmacogenetic testing to
      describe relevant aspects for further empirical studies. RESULTS: Apart from
      anticipated benefit, acceptance of pharmacogenetic testing might be influenced by
      the following: Expectation of negative psychosocial consequences, fear of
      discrimination or violation of privacy. Due to its great complexity,
      understanding of test results and explanation of their impact pose new challenges
      for physician-patient relations. Since most studies are conceptual, empirical
      studies exploring attitudes of patients/physicians and determining medical as
      well as economic value of pharmacogenetic testing are imperative.

PMID- 15856386
TI  - [Structure, realization and data synopsis of an observational study as part of
      the patient care evaluation programme on acupuncture (PEP-AC) drafted by German
      statutory insurance institutions].
AB  - This paper describes the concept and realization of a nation-wide observational
      study which is part of the patient care evaluation programme on acupuncture as
      part of a model project of German statutory insurance bodies. The study aimed
      describing medical care with acupuncture to estimate the incidence of adverse
      reactions as well as the treatment effects of acupuncture in chronically ill
      patients with headache, low back pain or osteoarthritic pain. It was also
      intended to analyse relations between treatment effects and specialties of the
      treating acupuncturists. During the two-year period of report 9,918
      acupuncturists took part in the study documenting 503,397 cases. A more
      comprehensive documentation is available for a sample of 10,366 patients with
      complete longitudinal data of 6,140 patients. The difficulties with data
      management and sampling technique are presented with reference to restricted
      capacities for monitoring. Furthermore the question of generalising of the
      results is discussed. There were differences in some respects (for example,
      frequencies of different indications) between the patient sample and the
      population of all patients included in the project. Patients also differed
      slightly with respect to the completeness of the longitudinal documentation. The
      results indicated that we cannot claim global representativeness for the sample
      based findings, but there is no reason to assume a "positive" selection.

PMID- 15856387
TI  - [Notes on the care of mentally ill residents in nursing homes in the Uelzen
      county district].
AB  - From 1999 to 2001 the "Centre of Applied Health Sciences" (University of
      Luneburg) carried out a research project in cooperation with the Psychiatric
      Hospital Hacklingen in Luneburg and the department of social psychiatry and
      psychotherapy of the Hanover College of Medicine. The project covered the
      prevalence of mental disorders among the residents of nursing and geriatric homes
      in the district of Uelzen including different aspects of medical, psychiatric and
      nursing care. The research was based on a survey including all residents of these
      institutions. The response rate was 925 of a total of 1,100 residents. Results
      showed that three-quarters of the residents had considerable and different
      psychiatric symptoms and that almost half of the residents suffered from symptoms
      of dementia. The provision of health care as well as nursing care for these
      residents are considerably deficient. Care facilities are hardly of therapeutical
      standard and guidelines. This refers in particular to treatment with psychoactive
      drugs. The (few) comparable studies show that -- with the exception of some pilot
      projects -- the situation in the district of Uelzen may be similar to that in
      other regions of Germany.

PMID- 15856388
TI  - [Migration and rehabilitation of mental diseases -- perspectives and limitations
      in the reporting of official data of service providers].
AB  - Health and social monitoring are important foundations of political decision
      making. In order to make statements about populations and subgroups different
      sources of information are generally used. The potential contribution which
      aggregated official health data of service providers can make is discussed in the
      exemplary context of the utilisation of medical rehabilitation of mental
      diseases. Age specific rates and age standardised ratios show a significantly
      increased utilisation of services for depression and somatoform disorders amongst
      women in general and the migrant population in particular. It is demonstrated
      that the interpretation of such results raises new research questions rather than
      providing explanations that could prove to be conducive for practical measures.
      In a methodological discussion it is stated that the reason for this has to be
      seen in the fact that important structures of action within the care system are
      concealed by the specific method of collecting and processing official health
      data. Nevertheless, conceivable interpretations are given regarding the psycho
      social living conditions of large parts of the migrant population as well as
      their difficulties in the interaction with the medical system. This enables the
      formulation of a hypothetical framework for further research which could help to
      clarify statistical phenomena found in the official data of service providers.

PMID- 15856389
TI  - [Eva-Reha: a computer software supporting outcome-based quality management in
      medical rehabilitation].
AB  - PURPOSE: Development of a computer software for supporting medical quallity
      management by documenting progression and results of medical rehabilitation in
      neurologic, orthopaedic, and geriatric patients. METHODS: The software "Eva-Reha"
      (Evaluation of Medical Rehabilitation) was generated using C ++ in a client
      server structure with Interbase being the underlying relational database
      management system. The software is network-compatible and runs under Windows NT
      and Windows 2000. RESULTS: "Eva-Reha", developed by the "Medizinischer Dienst der
      Krankenversicherung Rheinland-Pfalz (MDK RLP)" supports quality management
      systems in medical rehabilitation. Since 2003 the MDK RLP provides neurologic and
      geriatric rehabilitation centres with the software free of charge. With the help
      of "Eva-Reha" progression and results of medical rehabilitation can be displayed
      metrically, thus facilitating individual rehabilitation planning and supporting
      motivation of the rehabilitation team. Therapeutic strategies can be evaluated
      for different ICD-10-diagnoses or impairment groups. Moreover, "Eva-Reha"
      provides valuable data for administration and controlling purposes, e. g. age
      structure, case mix, impairment on admission and medical as well as
      rehabilitative procedures. The system generates a request for extension in a set
      form which facilitates communication between rehabilitation centres and sponsors.

PMID- 15856390
TI  - [Effectiveness of echinacin in therapy of chronic recurrent respiratory disease].
AB  - PURPOSE: Echinacea purpurea (echinacin) is frequently used in the therapy of
      chronic recurrent respiratory disease. The aim of this study was to show whether
      treatment of chronic recurrent respiratory disease with echinacin has a greater
      benefit in terms of effectiveness than therapy without an immunomodulator.
      MATERIALS AND METHODS: Frequency, duration of recurrence, resources used and
      patients' satisfaction was documented in order to assess benefit. In this
      prospective, non-randomised, multi-centre, nationwide, two-armed health services
      research study, data of 995 patients (782 echinacin-, 213 standard-cohort) with
      chronic recurrent respiratory disease were collected. The perspectives of
      statutory health insurance (SHI), patients and health policy were taken into
      consideration. RESULTS: The risk of falling ill was 2.3 fold higher and the
      duration of relapse 1.4 days more compared to the standard-cohort. There was a
      clinical and economical benefit from the therapy with echinacin for SHI and
      health policies. In contrast, patients experienced a greater financial burden.
      Average total costs per patient during the observation period of 3 months
      amounted to 238.35 in the standard-cohort and to 228.95 in the echinacin-cohort.
      Results of the intent-to-treat-analysis were reconfirmed in a per-protocol
      analysis. CONCLUSION: This health services-research-study taking the therapy of
      chronic recurrent respiratory disease with echinacin as an example has shown that
      even non-prescription drugs can have clinical and economic benefits.

PMID- 15856392
TI  - [The importance of the specialty "medical sociology" for teaching and research at
      university medical faculties in Germany].

PMID- 15856391
TI  - [Human biomonitoring investigations of organochlorine compounds -- PCB, DDE, HCB,
      beta- and gamma-HCH, PCDD/PCDF, Dioxin-like PCB's and polybrominated biphenyl
      ethers].
AB  - Although PCB and PCB-containing materials are not processed for a long time, PCB
      is under discussion again and again caused by the pollution of indoor
      environments. To objectify the discussion, the dates of the PCB-biomonitoring,
      the organochlorine-compounds (DDE, HCB, beta-/gamma -HCH, PCDD/PCDF) and the
      polybrominated biphenyl ethers concerning the investigations within the project
      "Sentinel Health Departments" in Baden-Wurttemberg are represented. Additionally
      results from children from Kazakhstan (Aral-Sea area) and from teachers which are
      working in PCB polluted schools as well as from a long term investigated test
      person are reported. Blood concentrations of the following compounds decreased
      from 1996/97 to 2002/03: the sum of the concentration of PCB 138,153 and 180
      decreased from 0.46 microg/L to 0.20 microg/L, DDE from 0.32 microg/L to 0.17
      microg/, HCB from 0.20 microg/L to 0.08 microg/L, beta-HCH below the level of
      detection, I-TEQ NATO to 4.8 pg/g blood fat, TEQ WHO (without PCB) to 5.5 pg/g
      blood fat, PCB 126 to 18,8,pg/g blood fat and PCB 169 to 12.8 pg/g blood fat. The
      influence of breast feeding and the gender on the level of the pollution is
      conspicious. No local correlations were found in Baden-Wurttemberg, but they were
      found in comparison with the results of Kazakhstan (Aral-Sea area). The
      difficulty to produce time series while the analyzing pollutants are more and
      more decreasing, as well as the change of the calculation base of the summation
      of parameters like I-TEQ NATO to TEQ WHO are discussed.

PMID- 15856394
TI  - [Complications of central venous access devices: outcome analysis of 2359
      implantations].
AB  - BACKGROUND AND OBJECTIVE: The implantation of venous access devices is of great
      importance in the treatment of oncological patients. Such systems allow a safe
      application of highly efficacious drugs with great comfort for the patient.
      Knowing the rate of complications, is wide indication for such implantations
      justified? METHODS: From July 1 (st), 1995 to December 31 (st), 2003, 2359 access
      systems were implanted under local anaesthesia mainly for chemotherapy. All
      patients were examined for postoperative complications and followed up throughout
      the complete duration of treatment. RESULTS: In 147 out of 2359 patients we saw
      complications which had to be treated. In all cases treatment was effective. No
      patient suffered severe consequences. Main complications were infections (2.4%),
      and thrombosis (2.0%). In 17 cases (0.7%) bleeding occurred postoperatively which
      required reoperation in 12 patients. We saw 5 instances of pneumothorax after
      puncture of the subclavian vein four of which were drained. In 11 cases (0.5%) we
      found dislocation of the catheter. In 10 cases we were able to reposition the
      catheter by open procedure, and only in one patient was repositioning not
      successful. In three cases (0.1%) there occurred disconnection between access
      catheter and access chamber with extravasation in two cases. In one patient the
      catheter had to be removed surgically out of the right atrium. CONCLUSION: The
      implantation of venous access systems under local anaesthesia is a safe procedure
      with a low rate of complications and allows permanent venous access with very
      acceptable comfort for the patient. The indication for implantation can therefore
      be set liberally.

PMID- 15856395
TI  - [Integrated skills laboratory concept for undergraduate training in internal
      medicine].
AB  - BACKGROUND AND OBJECTIVE: An amendment to the German medical curriculum in April
      2002 will place basic practical skills at the centre of medical training. We
      report here on the implementation and evaluation of an obligatory, tutor-guided,
      and integrated skills laboratory concept in the field of internal medicine.
      METHODS: To test the effectiveness of a skills laboratory training on OSCE
      performance a pilot study was carried out. The experimental group, of 77
      students, participated in seven sessions of communication training, skills
      laboratory training, and bedside teaching, each lasting one and a half hours. The
      control group of 66 students had as many sessions but was only offered bedside
      teaching. The evaluation of acceptance of skills' training as well as the related
      increase in individual competence is on-going (summer term 2004: n = 176
      students). RESULTS: The integrated skills laboratory concept was rated at 3.5 (SD
      = 1.2) on a 5-point scale and was acknowledged as practice-oriented (M = 4.2; SD
      = 1.0) and relevant for doctors' everyday lives (M = 3.6; SD = 1.1). Increased
      levels of competence according to individual self-evaluations proved to be highly
      significant (p<.001), and results of the pilot study showed that the experimental
      group had a significantly better OSCE performance than the control group
      (p<.001). CONCLUSION: This pilot study shows that curriculum changes promoting
      basic clinical skills are effective and lead to an improved practical education
      of tomorrow's physicians. The integrated skills laboratory concept is well
      accepted and leads to a relevant increase in competence in the practice of
      internal medical. The presented skills laboratory concept in internal medicine is
      proving to be a viable and efficient learning tool.

PMID- 15856396
TI  - [Surprising findings in the colon 15 years after a holiday in Africa].
AB  - HISTORY AND ADMISSION FINDINGS: A 65-year-old woman was admitted to hospital with
      abdominal discomfort for several years. Travel history revealed two 4-week stays
      in Mwanza/Tanzania 15 and 17 years earlier. INVESTIGATIONS: Laboratory tests
      showed eosinophilia and an increase of IgE and antibodies against Schistosoma
      mansoni (IHA, EIA). Stool was negative for worm eggs. Colonoscopy revealed in
      several parts small nodules and increased vascularisation. Histology showed
      granulomas and eggs of Schistosoma mansoni. TREATMENT AND COURSE: Anthelmintic
      therapy with praziquantel was given. After that the patient was well. One year
      later, follow-up endoscopy and histology were the same as previously. Another
      course of Praziquantel was given. A year later the patient was still well.
      CONCLUSION: Even after several years the rare case of intestinal schistosomiasis
      should be considered in patients with a history of travel in endemic regions. In
      case of negative stool specimen biopsies of the colon and rectum should be taken.

PMID- 15856397
TI  - [State of the art diagnosis and therapy of acute chest pain].

PMID- 15856398
TI  - [Sudden cardiac death in familial hypertrophic cardiomyopathy. Identification of
      high-risk patients].
AB  - Hypertrophic cardiomyopathy (HCM) is a relatively frequent, genetically
      determined primary cardiomyopathy, characterized by most often asymmetric
      hypertrophy of the ventricular septum with or without systolic obstruction of the
      left ventricular outflow tract. HCM is a genetically heterogeneous disease, with
      12 different disease-causing genes beeing indentified to date. Histologically the
      disease is characterized by hypertophy and disarray of myofibrils as well as by
      an increase in myocardial fibrosis. Clinically, these changes may lead to
      palpitations, dyspnoe on exertion, and/or angina pectoris. However, they also
      lead to an increased propensity to the development of severe ventricular
      tachyarrhythmias and sudden cardiac death. The incidence of sudden death is
      significantly increased in HCM, particularly in affected young subjects. Risk
      stratification in HCM should include a complete clinical-cardiological evaluation
      that should also consider new diagnostic features, e. g. MR imaging. Major risk
      factors for sudden cardiac death include a survived cardiac arrest (ventricular
      fibrillation), non-sustained and sustained ventricular tachycardia, a history of
      premature familial sudden death, unexplained syncope, an abnormal blood pressure
      response on exercise, and left ventricular thickness greater than or equal to 3
      cm. Ideally, risk stratification should also include genetic testing, since some
      gene mutations seem to be associated with a higher risk for sudden cardiac death
      than others. However, genetic testing in HCM in not yet available on a routine
      basis. The implantation of a cardioverter/defibrillator is first-line therapy in
      patients with documented ventricular tachycardia/fibrillation or patients who
      have survived sudden cardiac death. These devices also play an important role in
      the primary prevention of sudden cardiac death in HCM. Algorithms and scores are
      available to estimate the risk of sudden death, however, the decision to implant
      a cardioverter/defibrillator remains an individual decision in every single
      patient.

PMID- 15856399
TI  - [Indication--reasoning structure for medical actions].

PMID- 15856400
TI  - [Prevention of cardiovascular diseases with omega-3 fatty acids and viramins?].

PMID- 15856401
TI  - [Subclinical hypothyroidism in children].

PMID- 15856402
TI  - Dietary phytoestrogens: potential selective estrogen enzyme modulators?
AB  - Between one-third to one-half of all breast cancers are steroid sensitive.
      Steroid-pathway enzymes (sulfatase, 17beta-hydroxysteroid dehydrogenases,
      aromatase and sulfotransferases) are thus prime candidates for therapeutic
      approaches based on the control of intacrine activity. Some phytoestrogens,
      ubiquitous in our diet, are inhibitors of these enzymes. Such a therapeutic
      potential has stimulated research and progress has been achieved during the last
      years. Complementary to previous reviews on phytoestrogens, this contribution
      covers the estrogen pathway inhibition effects of these compounds and special
      attention will be given to isoflavonoids, flavonoids and lignans. Furthermore,
      the research on structurally-related compounds as therapeutic agents will be
      discussed briefly.

PMID- 15856403
TI  - Antioxidant effects of diarylheptanoid derivatives from Alnus japonica on human
      LDL oxidation.
AB  - Two diarylheptanoids, oregonin (1) and hirsutanone (2), were isolated by bioassay
      guided fractionation of the methanol extracts of the leaves of Alnus japonica
      Steud and their structures were elucidated from their spectroscopic data.
      Compounds 1 and 2 exhibited significant low-density lipoprotein (LDL)-antioxidant
      activities, e. g., thiobarbituric acid-reactive substances (TBARS) assay (1: IC50
      = 3.2 microM, 2: IC50 = 1.5 microM), lag time (1 : 162 min, 2 : 230 min at 2.0
      microM, control: 63 min), relative electrophoretic mobility (REM, inhibition of 1
      : 71%, 2 : 75% at 10 microM), apoB-100 fragmentation (inhibition of 1 : 27.3%, 2
      : 40.3% at 10 microM) and macrophage-mediated LDL oxidation (inhibition of 1 :
      82%, 2 : 84% at 1 microM).

PMID- 15856404
TI  - Anti-inflammatory activity of sugiol, a diterpene isolated from Calocedrus
      formosana bark.
AB  - Sugiol is a diterpene which was isolated and purified from alcohol extracts of
      the bark of Calocedrus formosana Florin (Cupressaceae). Although sugiol has low
      inhibitory activity against the DPPH radical, it could effectively reduce
      intracellular reactive oxygen species (ROS) production in lipopolysaccharide
      (LPS)-stimulated macrophages. The present study investigated the potential anti
      inflammatory activity of sugiol, and the relationship between signal transduction
      and inflammatory cytokines in vitro. A dose of 30 microM of sugiol was
      effectively inhibitory for proIL-1beta, IL-1beta and TNF-alpha production,
      suggesting that sugiol is bioactive against inflammation. Moreover, sugiol
      reveals a capacity for suppressing the activation of mitogen-activated protein
      kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun NH2
      terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38) activated
      by LPS-stimulation in J774A.1 murine macrophages. A low dosage of 10 microM of
      sugiol completely inhibited ERK1/2 phosphorylation, while 30 microM effectively
      inhibited JNK1/2 and p38 phosphorylation in LPS-stimulated macrophages. In
      addition, sugiol significantly inhibited LPS-induced ROS production. Our studies
      suggest that sugiol's efficacy in inhibiting the inflammatory cytokines of IL
      1beta and TNF-alpha could be attributed to a reduction of the ROS that leads to a
      decrease in the phosphorylation of MAPKs.

PMID- 15856405
TI  - Induction of apoptosis by apicularen A in human promyelocytic leukemia cell line
      HL-60.
AB  - Apicularen A, a macrolide isolated from the myxobacterial genus Chondromyces,
      suppressed the proliferation of human promyelocytic leukemia cells (HL-60 cells),
      increased the release of lactate dehydrogenase and induced condensation and
      fragmentation of chromatin at 1 to 100 nM. In addition, it induced the DNA
      fragmentation, increased the percentage of annexin V-stained cells, and cleaved
      poly(ADP-ribose) polymerase (PARP), a substrate of caspase. In contrast,
      apicularen B, an N-acetylglucosamine glycoside of apicularen A, had no such
      effects at 100 nM. These findings indicated that apicularen A induces apoptosis
      in HL-60 cells by activating caspases. Phosphorylation of p44/42 MAPK, p38 MAPK
      and Akt was not induced by apicularen A at 100 nM, suggesting that the apicularen
      A-induced apoptosis in HL-60 cells is not regulated by the activation of p44/42
      MAPK, p38 MAPK or Akt. Furthermore, by acridine orange staining of the cells, it
      was suggested that apicularen A but not apicularen B inhibits vacuolar-type H+
      ATPase.

PMID- 15856406
TI  - Antimicrobial activity of 6-oxophenolic triterpenoids. Mode of action against
      Bacillus subtilis.
AB  - Zeylasteral and demethylzeylasteral are 6-oxophenolic triterpenoids isolated from
      the root of Maytenus blepharodes, which have antimicrobial activity against Gram
      positive bacteria and the yeast Candida albicans. The time-kill curves for
      zeylasteral and demethylzeylasteral at concentrations twice their MICs, against
      Bacillus subtilis showed that the colony forming units were reduced in 3-log10
      and > 4-log10 respectively. This reduction was dependent on inoculum size and the
      growth phase of cells, and was greater when the compounds were incorporated in
      the exponential phase, indicating a bacteriolytic effect. Treatment with both
      agents, particularly with zeylasteral (20 microg/mL) caused a reduction of
      optical density at 550 nm. With regard to the synthesis of DNA, RNA, protein and
      cell wall, the compounds exhibited the fastest inhibition against cell wall
      synthesis. Thus, the predisposition to lysis, the morphological changes seen by
      microscopy, and the complete inhibition in the incorporation the N-acetyl-d-[1 -
      14C]glucosamine, suggest that the phenolic compounds compromise the cell wall
      synthesis and/or cytoplasmic membrane.

PMID- 15856407
TI  - Smooth muscle relaxant action of benzyl benzoates and salicylic acid derivatives
      from Brickellia veronicaefolia on isolated guinea-pig ileum.
AB  - A dichloromethane-MeOH extract prepared from the aerial parts of Brickellia
      veronicaefolia inhibited the spontaneous contractions (IC50 = 39.22 microg/mL) of
      the guinea-pig ileum. Bioassay-guided fractionation of the extract led to the
      isolation of three new benzoic acid derivatives, 1,2-bis-O-(2-methoxybenzoyl)
      beta-d-glucopyranoside (1), 3-(beta-glucopyranosyloxy)benzyl 2,6
      dimethoxybenzoate (2) and 3-hydroxybenzyl 2,6-dimethoxybenzoate (3), together
      with the known compounds taraxasteryl acetate (4), 4-allyl-2-methyloxyphenyl-beta
      glucopyranoside (5), 2-hydroxy-6-methoxybenzoic acid (6), 2-methoxybenzoic acid
      (7), chamazulene (8), 2-methoxybenzyl 2-hydroxybenzoate (9), benzyl 2,6
      dimethoxybenzoate (10), 3-methoxybenzyl 2-hydroxy-6-methoxybenzoate (11), benzyl
      2-hydroxy-6-methoxybenzoate (12), benzyl 2,3,6-trimethoxybenzoate (13), benzyl 2
      hydroxy-3,6-dimethoxybenzoate (14) and 3-methoxybenzyl 2,6-dimethoxybenzoate
      (15). The isolates were characterized by spectral means. Compounds 2 - 6, 8 - 11,
      14 and 15 induced a concentration-dependent inhibition of the spontaneous
      contractions of the guinea-pig ileum with IC50 values ranging from 1.49 to 4.96
      microM. Their activity was comparable to that of papaverine (IC50 = 4.23 microM).

PMID- 15856408
TI  - Evaluation of the antimicrobial effects of several isothiocyanates on
      Helicobacter pylori.
AB  - The antibacterial activity of sulforaphane [4-(methylsulfinyl)butyl
      isothiocyanate] has been previously described. We have analysed the activities of
      12 isothiocyanates (ITC) including sulphoraphane on 25 strains of Helicobacter
      pylori using an agar dilution assay. In addition, bactericidal effects against H.
      pylori were determined for the 6 most active ITCs, both directly and against
      intracellular bacteria in cultured human epithelial (HEp-2) cells. The MIC90
      values for these ITCs ranged between 4 and 32 microg/mL and four of the most
      potent compounds exhibited bactericidal activity against both extra- and
      intracellular bacteria. Overall, our data indicate that ITCs have a potent
      antibacterial effect against H. pylori and these naturally occurring
      phytochemicals might have potential as novel therapeutic agents for H. pylori
      eradication.

PMID- 15856409
TI  - No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by
      treatment with a low-hyperforin St John's wort extract.
AB  - We evaluated the pharmacokinetic interaction between a low-hyperforin St John's
      wort (SJW) extract and alprazolam, caffeine, tolbutamide, and digoxin. Previous
      reports on other SJW products had shown remarkably decreased plasma
      concentrations of certain co-medicated drugs, which was attributed to an inducing
      effect of SJW on cytochrome P-450 (CYP) and p-glycoprotein (p-gp) activity. Two
      randomised, placebo-controlled studies were performed with 28 healthy volunteers
      (age 18 - 55 years) in each study. In study A, single doses of alprazolam (1 mg;
      substrate of CYP3A4) and caffeine (100 mg; CYP1A2) were given on days 1 and 11.
      In study B, single doses of tolbutamide (500 mg, days 1 and 11; CYP2C9) and
      multiple doses of digoxin (0.75 mg on days -2 and -1, 0.25 mg/die on days 1 to
      11; p-gp) were given. The participants received SJW (Esbericum capsules; 240
      mg/die of extract, 3.5 mg hyperforin) or placebo on days 2 to 11. Blood for
      pharmacokinetic analysis was drawn on days 1 and 11. No statistically significant
      differences were found in the primary kinetic parameter, AUC0 - 24, of
      alprazolam, caffeine (AUC0 - 12), paraxanthine, tolbutamide, 4
      hydroxytolbutamide, and digoxin between the placebo group and the SJW group at
      the end of the study. The SJW-induced change in AUCs was less than 12 % of the
      initial median AUC of the participants in studies A and B, thus clinically
      irrelevant. On day 11, trough concentrations were 2.0 (range 0.6 - 4.1) microg/L
      and 1.0 (0.2 - 3.9) microg/L for hypericin and pseudohypericin, respectively,
      whereas hyperforin concentrations were below the quantification limit (< 1
      microg/L). Kinetics of investigated probe drugs were only marginally influenced
      by concomitant treatment with Esbericum capsules. This may be due in particular
      to the low hyperforin plasma concentration as this SJW component has been shown
      to activate the PXR receptor which regulates expression of CYP3A4 and p-gp. Our
      findings corroborate the view that reports about interactions of other SJW
      extracts seem not to be predictive for the product we studied.

PMID- 15856410
TI  - Anti-inflammatory effects of magnolol and honokiol are mediated through
      inhibition of the downstream pathway of MEKK-1 in NF-kappaB activation signaling.
AB  - Propionibacterium acnes, an anaerobic pathogen, plays an important role in the
      pathogenesis of acne and seems to initiate the inflammatory process by producing
      proinflammatory cytokines. In order to demonstrate the anti-inflammatory effects
      and action mechanisms of magnolol and honokiol, several methods were employed.
      Through DPPH and SOD activity assays, we found that although both magnolol and
      honokiol have antioxidant activities, honokiol has relatively stronger
      antioxidant activities than magnolol {[for DPPH assay, % of DPPH bleaching of
      magnolol and honokiol (500 microM magnolol: 19.8%; 500 microM honokiol: 67.3%)];
      [for SOD assay, SOD activity (200 microM magnolol: 53.4%; 200 microM honokiol:
      64.3%)]}. Moreover, the production of interleukin-8 (IL-8) and tumor necrosis
      factor-alpha (TNF-alpha) induced by P. acnes in THP-1 cells, a human monocytic
      cell line, was reduced by magnolol and honokiol {[for IL-8 (10 microM magnolol:
      42.7% inhibition; 10 microM honokiol: 51.4% inhibition)]; [for TNF-alpha (10
      microM magnolol: 20.3% inhibition; 10 microM honokiol: 39.0% inhibition)]}.
      Cyclooxygenase-2 (Cox-2) activity was also suppressed by them [(15 microM
      magnolol: 45.8% inhibition), (15 microM honokiol: 66.3% inhibition)]. Using a
      nuclear factor-kappaB (NF-kappaB) luciferase reporter assay system and Western
      analysis, we identified that magnolol and honokiol exert their anti-inflammatory
      effects by inhibiting the NF-kappaB element, which exists in Cox-2, IL-8, and TNF
      alpha promoters [(15 microM magnolol: 44.8% inhibition), (15 microM honokiol:
      42.3% inhibition)]. Of particular note is that magnolol and honokiol operate
      downstream of the MEKK-1 molecule. Together with their previously known
      antibacterial activity against P. acnes and based on these results, we suggest
      that magnolol and honokiol may be introduced as possible acne-mitigating agents.

PMID- 15856411
TI  - New phenylpropane and anti-inflammatory diterpene derivatives from Amentotaxus
      formosana.
AB  - One new diterpene, 8(14),15-sandaracopimaradiene-2alpha,3beta,18-triol (1), two
      new phenylpropane derivatives, i.e., (E)-methyl 2-(3,4-methylene-dioxyphenyl)-3
      methoxypropenoate (2) and (E)-2-(3,4-methylene-dioxyphenyl)-3-methoxypropenoic
      acid (3), and two known diterpenes, ent-8(14),15-sandaracopimaradiene-2alpha,18
      diol (4) and 8(14),15-sandaracopimaradiene-2alpha,18,19-triol (5), were isolated
      from the heartwoods and barks of Amentotaxus formosana, respectively. The anti
      inflammatory activity of the diterpenes 1, 4, and 5 was assessed in vitro by
      determining their inhibitory effects on the chemical mediators released from mast
      cells, neutrophils, macrophages, and microglial cells. Compounds 1, 4, and 5
      showed significant concentration-dependent inhibitory effects on the release of
      beta-glucuronidase from rat neutrophils in response to formyl-Met-Leu
      Phe/cytochalasin B (fMLP/CB) with IC50 values of 5.5 +/- 1.8, 8.4 +/- 2.9 and
      19.2 +/- 3.3 microM, respectively. Compounds 1 and 5 also showed significant
      concentration-dependent inhibitory effects on superoxide anion generation in rat
      neutrophils stimulated with fMLP/CB and phorbol 12-myristate 13-acetate (PMA)
      with IC50 values of 12.6 +/- 1.2 and 9.4 +/- 1.7, and 10.7 +/- 3.3 and 12.9 +/-
      0.9 microM, respectively.

PMID- 15856412
TI  - Cytotoxic diterpenoids from the roots of Euphorbia ebracteolata.
AB  - Three new diterpenoids, yuexiandajisu D (1), E (2) and F were isolated from the
      roots of Euphorbia ebracteolata, along with eight known diterpenoids, jolkinolide
      B (4), jolkinolide A, ent-11alpha-hydroxyabieta-8(14),13(15)-dien-16,12alpha
      olide (6), ent-(13S)-hydroxyatis-16-ene-3,14-dione, ent-3beta,(13S)-dihydroxyatis
      16-en-14-one, ent-3-oxokaurane-16alpha,17-diol, ent-16alpha,17-dihydroxyatisan-3
      one and ent-atisane-3beta,16alpha,17-triol. The structures of all compounds were
      deduced using spectroscopic methods and confirmed for 1 and 2 by single-crystal X
      ray diffraction. A biogenetic pathway for the formation of 1 and 2 is proposed
      briefly. Cytotoxic activities were evaluated against ANA-1, B 16 and Jurkat tumor
      cells. Jolkinolide B (4) displayed modest activity on ANA-1, B 16 and Jurkat
      tumor cells with IC50 values 4.46 x 10(-2), 4.48 x 10(-2), 6.47 x 10(-2) microM,
      and ent-11alpha-hydroxyabieta-8(14),13(15)-dien-16,12alpha-olide (6) showed
      significant activity against ANA-1 and Jurkat cells with IC50 values 7.12 x 10(
      3) and 1.79 x 10(-2) microM. Compound 1 was found to be slightly active against
      ANA-1 cells with an IC50 value 2.88 x 10(-1)microM. Structure-activity
      relationships of isolated compounds are also discussed.

PMID- 15856414
TI  - Six new triterpenoid saponins from the root and stem bark of Cephalanthus
      occidentalis.
AB  - From the root and stem bark of Cephalanthus occidentalis L., a common American
      wetland species, six new triterpenoid saponins (1 - 6), together with 29 known
      compounds were isolated and identified. On the basis of spectroscopic analysis
      and chemical degradation, the structures of new compounds were elucidated as 3-O
      beta-glucopyranosylcincholic acid (1), cincholic acid 28-O-beta-glucopyranosyl
      ester (2), 3-O-beta-glucopyranosyl-(1-->4)-beta-fucopyranosylcincholic acid (3),
      3-O-beta-glucopyranosyl-(1-->4)-beta-fucopyranosylcincholic acid 28-O-beta
      glucopyranosyl ester (4), 3-O-beta-glucopyranosylcincholic acid 28-O-alpha
      arabinopyranosyl-(1-->2)-beta-glucopyranosyl ester (5), and 3-O-beta
      glucopyranosylquinovic acid 28-O-alpha-arabinopyranosyl-(1-->2)-beta
      glucopyranosyl ester (6).

PMID- 15856415
TI  - C-glycosylflavones from the aerial parts of Eleusine indica inhibit LPS-induced
      mouse lung inflammation.
AB  - The infusion of aerial parts (EI) of Eleusine indica Gaertn (Poaceae) is used in
      Brazil against airway inflammatory processes like influenza and pneumonia. Pre
      treatment with 400 mg/kg of crude extract inhibited 98% of lung neutrophil
      recruitment in mice exposed to aerosols of lipopolysaccharide (LPS) from Gram
      negative bacteria, in a dose-dependent manner. At 400 microg/kg, schaftoside (6-C
      beta-glucopyranosyl-8-C-alpha-arabinopyranosylapigenin) and vitexin (8-C-beta
      glucopyranosylapigenin), isolated from EI, inhibited 62% and 80% of lung
      neutrophil influx, respectively. These results may justify the popular use of E.
      indica against airway inflammatory processes.

PMID- 15856416
TI  - Antifungal properties of surangin B, a coumarin from Mammea longifolia.
AB  - The natural product electron transport inhibitor surangin B was examined for its
      ability to inhibit in vitro mycelial growth and spore germination in several
      species of fungi. As an inhibitor of mycelial growth, surangin B showed strongest
      activity against Rhizoctonia solani (IC50 = 3.8 microM) and Botrytis cinerea
      (IC50 = 11.2 microM). Inhibitory effects were less pronounced in Alternaria
      dauci, Fusarium oxysporum and Penicillium sp. (IC50 values > 30 microM) and
      absent in Trichoderma harzianum. Surangin B reduced the level of spore
      germination in Fusarium oxysporum (IC50 = 2.3 microM) and Botrytis cinerea (IC50
      = 1.4 microM), although Alternaria dauci was considerably more tolerant of this
      coumarin (IC50 = 500 microM). Our results indicate that surangin B may have
      potential as an antifungal agent.

PMID- 15856417
TI  - In vitro antileishmanial activity of diphyllin isolated from Haplophyllum
      bucharicum.
AB  - Diphyllin isolated from Haplophyllum bucharicum Litv. (Rutaceae), an endemic
      plant of Uzbekistan, displayed a moderate antiproliferative activity towards
      human monocytes (IC50 = 35.2 microM) and Leishmania promastigotes (IC50 = 14.4
      microM), by a mechanism of action that involved interaction with macromolecules
      and resulted in cell cycle arrest in the S-phase and inhibition of protein
      synthesis. In the intracellular amastigote form of the parasite, diphyllin
      exerted a strong specific inhibitory activity (IC50 = 0.2 microM) resulting from
      the inhibition of parasite internalization within macrophages. This property was
      mainly due to modulation of macrophage phagocytosis and, to a lesser extent, it
      also involved interference with surface molecules of the promastigote membrane.

PMID- 15856418
TI  - Cytotoxic chromenes from Myriactis humilis.
AB  - Two new chromenes, myriachromene and 2,2-dimethyl-6,7-methylenedioxy-2H-chromene,
      together with ten known compounds including alpha-tocopherylquinone, alpha
      tocopherol acetate, diphenyl sulfone, beta-carotene, chondrillasterol, beta
      sitosterol, beta-sitostenone, vanillin, and vanillic acid were isolated from the
      whole plant of Myriactis humilis. The structures of these new compounds were
      determined through spectral analyses. Among the isolates, four compounds
      exhibited cytotoxicity (ED50 values < 4 microg/mL) against P-388 or HT-29 cell
      lines in vitro.

PMID- 15856419
TI  - Xanthones from the roots of Polygala caudata and their antioxidation and
      vasodilatation activities in vitro.
AB  - Three new xanthones, 2-hydroxy-1,6,7-trimethoxyxanthone (1), 1,4-dimethoxy-2,3
      methylenedioxyxanthone (2), and 7-hydroxy-1,2-dimethoxyxanthone (3), together
      with five known compounds, 2,7-dihydroxy-1-methoxyxanthone (4), 1-methoxy-2,3
      methylenedioxyxanthone (5), 7-hydroxy-1-methoxyxanthone (6), euxanthone (1,7
      dihydroxyxanthone) (7), and gentitein (1,3,7-trihydroxyxanthone) (8), were
      isolated from the roots of Polygala caudata. Their structures were established on
      the basis of spectral evidence. In the antioxidation activity screening in vitro
      with luminol chemiluminescence methods, compounds 1 - 5 and 7 and 8 showed H2O2
      scavenger activity, with a scavenging effect of 58.4 - 94.5% at 10 microg/mL, and
      26.0 - 84.7% at 2 microg/mL. Compounds 4 and 8 also exhibited scavenging effects
      on the reactive oxygen free radicals produced by macrophage respiratory bursts,
      with a scavenging effect of 71.7% and 63.4% at 10 microg/mL, 41.2% and 47.8% at 2
      microg/mL, respectively. In the vasodilatation assay, compounds 4 - 7 exhibited
      relaxing activity on the contractions evoked by KCl in Wistar rat thoracic aorta
      rings in a dose-dependent manner.

PMID- 15856420
TI  - Enhanced hypotensive effects of the essential oil of Ocimum gratissimum leaves
      and its main constituent, eugenol, in DOCA-salt hypertensive conscious rats.
AB  - The cardiovascular effects of intravenous (i.v.) treatment with the essential oil
      of Ocimum gratissimum (EOOG) and its main constituent, eugenol (Eug) were
      investigated in the experimental model of deoxycorticosterone acetate (DOCA-salt)
      hypertensive rats. In both conscious DOCA-salt hypertensive rats and their
      uninephrectomized controls, i.v. bolus injections of EOOG (1 - 20 mg/kg) or Eug
      (1 - 10 mg/kg) induced dose-dependent hypotension and bradycardia. Treatment with
      DOCA-salt significantly enhanced the maximal decreases in mean aortic pressure
      (MAP) elicited by hexamethonium (30 mg/kg, i.v.) as well as the hypotensive
      responses to both EOOG and Eug without affecting the bradycardia. However, the
      enhancement of EOOG-induced hypotension in hypertensive rats remained unaffected
      by i.v. pretreatment with either hexamethonium (30 mg/kg) or methylatropine (1
      mg/kg). These results show that i.v. treatment with EOOG or Eug dose-dependently
      decreased blood pressure in conscious DOCA-salt hypertensive rats, and this
      action is enhanced when compared with uninephrectomized controls. This
      enhancement appears related mainly to an increase in EOOG-induced vascular smooth
      relaxation rather than to enhanced sympathetic nervous system activity in this
      hypertensive model.

PMID- 15856421
TI  - A xylogalactofucan from the brown seaweed Spatoglossum schroederi stimulates the
      synthesis of an antithrombotic heparan sulfate from endothelial cells.
AB  - The brown seaweed Spatoglossum schroederi (Dictyotaceae) contains three main
      fucans (fucans A, B and C) with different mobility in electrophoresis. The fucan
      with highest mobility (fucan C) was precipitated with 2.0 volumes of acetone,
      purified using a combination of ion exchange chromatography and electrophoresis.
      It showed an MW of 24 kDa determined by HPLC and Sephadex G-75 chromatography and
      migrates as a single band in three distinct electrophoretic systems. This fucan
      contains fucose, xylose, galactose and sulfate in a molar ratio 1 : 0.6 : 2:2.3.
      The fucan has neither anticoagulant (from 10 to 100 microg) nor hemorrhagic
      activities (100 microg/mL). In addition, fucan C is neither cytotoxic nor
      cytostatic. However, fucan C (100 microg/mL) stimulated the synthesis of an
      antithrombotic heparan sulfate from endothelial cells of rabbit aorta. The
      results suggest that fucan C might be used as an antithrombotic therapeutic
      compound.

PMID- 15856422
TI  - Structure analysis and antitumor activity of (1-->3)-beta-d-glucans
      (cordyglucans) from the mycelia of Cordyceps sinensis.
AB  - The cell wall polysaccharides from Cordyceps sinensis were obtained from the
      fresh samples of the mycelia, the material was released by successive extractions
      with hot water and 0.05 M sodium hydroxide solutions. The extracts were
      fractionated by ion-exchange and gel-filtration chromatography, respectively.
      Analysis of the first fraction showed that cordyglucans were the unique
      component. Cordyglucans were found to exhibit potent antitumor activity, this
      activity could be correlated to their (1-->3)-beta-d-glucan linkages.

PMID- 15856423
TI  - Identification of Fritillaria pallidiflora using diagnostic PCR and PCR-RFLP
      based on nuclear ribosomal DNA internal transcribed spacer sequences.
AB  - Fritillaria pallidiflora Schrenk (Liliaceae) is a commonly used antitussive herb.
      There are 9 species of Fritillaria recorded as herbal drugs in the Chinese
      Pharmacopoeia. The other species are often marketed as F. pallidiflora, and thus,
      the therapeutic effects of F. pallidiflora are not achieved. Methods to
      distinguish F. pallidiflora from the 8 other species of Fritillaria are limited
      by the current morphological and chemical methods. In this study, we report two
      molecular authentication methods based on the sequences of nuclear ribosomal DNA
      internal transcribed spacer (nrDNA ITS) regions. For diagnostic PCR, we designed
      a pair of species-specific primers to authenticate F. pallidiflora. The PCR
      program consisted of only two steps for every repeated cycle. For PCR-RFLP, we
      identified a distinctive site which can be recognized by the restriction
      endonuclease Eco81I in the nrDNA ITS1 region of F. pallidiflora. PCR-RFLP
      analysis was established to differentiate F. pallidiflora from the other species
      of Fritillaria. These methods provide effective and accurate identification of F.
      pallidiflora.

PMID- 15856424
TI  - High-resolution H/D exchange studies on the HET-s218-295 prion protein.
AB  - In a search for improved resolution of hydrogen/deuterium (H/D) exchange
      experiments analyzed by mass spectrometry (HXMS), we evaluated two methodologies
      for a detailed structural study of solvent accessibility in the case of the HET
      s(218-295) prion protein. For the first approach, after incubation in the
      deuterated solvent, aggregated HET-s(218-295) was digested with pepsin and the
      generated peptides were analyzed by nanospray mass spectrometry in an ion trap,
      with and without collision-induced dissociation (CID). We compared deuterium
      incorporation in peptides as determined on peptide pseudomolecular ions and on b
      and y fragments produced by longer peptides under CID conditions. For both b and
      y fragment ions, an extensive H/D scrambling phenomenon was observed, in contrast
      with previous studies comparing CID-MS experiments and (1)H NMR data. Thus, the
      spatial resolution of HXMS experiments could not be improved by means of MS/MS
      data generated by an ion trap mass spectrometer. In a second approach, the
      incorporation of deuterium was analyzed by MS for 76 peptides of the HET-s(218
      289) peptide mass fingerprint, and the use of shared boundaries among peptic
      peptides allowed us to determine deuteration levels of small regions ranging from
      one to four amino acids. This methodology led to evidence of highly protected
      regions along the HET-s(218-295) sequence.

PMID- 15856425
TI  - Mammalian sperm phosphodiesterases and their involvement in receptor-mediated
      cell signaling important for capacitation.
AB  - This study investigated the presence and function of intracellular cyclic
      nucleotide phosphodiesterases (PDEs) in mature mouse spermatozoa. PCR analysis
      detected gene transcripts for most of the 11 known PDE families in whole testis,
      but mainly for PDEs 1, 3, 6, and 8 in spermatozoa. Using specific antibodies, the
      strongest evidence was obtained for PDE proteins 1, 4, 6, 8, 10, and 11 in both
      sperm lysates and intact cells. These showed a range of subcellular
      localizations, with PDE 1A being primarily in the flagellum but PDEs 4D and 10A
      being in both the acrosomal region and the flagellum, similar to specific G
      proteins and adenylyl cyclases implicated in cAMP regulation during capacitation.
      In live spermatozoa, inhibitors selective for PDE 1 (MMPX) and 4 (rolipram)
      significantly increased cAMP over control levels but only rolipram significantly
      stimulated capacitation and in-vitro fertilizing ability; this suggests that
      compartmentalization has functional implications since only PDE 4 was abundant in
      both head and flagellum. Treatment of spermatozoa with CGS 21680, a stimulatory
      adenosine receptor agonist, significantly reduced cAMP-PDE activity at the same
      time-point when it causes increased cAMP. Thus, certain receptor-regulated cAMP
      processes in spermatozoa may be controlled by changes in both PDE and cyclase
      activities. In addition to demonstrating for the first time that some of the more
      recently discovered PDE isoforms, including PDE 6 (usually associated with the
      retina), are present in mature spermatozoa, this study provides clear evidence
      that the intracellular location of specific PDEs has important functional
      significance during capacitation and fertilization.

PMID- 15856426
TI  - Neoplastic meningitis in patients with adenocarcinoma of the gastrointestinal
      tract.
AB  - BACKGROUND: Neoplastic meningitis (NM) occurs in 5-10% of patients with malignant
      disease. Little is known about the outcomes of patients with gastrointestinal
      (GI) malignancies who develop NM. For this report, the authors characterized the
      clinical course and attempted to identify prognostic factors in patients with NM
      due to primary malignancies of the GI tract. METHODS: In this retrospective
      study, 21 patients with GI primary tumors and NM were identified: Their medical
      records and imaging studies were reviewed. RESULTS: The patient population was
      composed of patients with gastric adenocarcinoma (n = 8 patients), esophageal
      adenocarcinoma (n = 7 patients), colon and/or rectal adenocarcinoma (n = 5
      patients), and pancreatic adenocarcinoma (n = 1 patient). The median overall
      survival after the initial diagnosis of adenocarcinoma was 55 weeks (range, 8-884
      wks), and the median survival after the diagnosis of NM was 7 weeks (range, 0-64
      wks). Four patients died during palliative radiotherapy. No factors identified
      had an impact on outcome, including symptoms, physical findings at diagnosis,
      imaging characteristics, or cerebrospinal fluid findings. Univariate analysis
      showed a trend toward better outcomes for patients who received any kind of
      treatment directed toward the NM. CONCLUSIONS: Patients with NM from GI tract
      adenocarcinomas universally had poor outcomes. Until NM can be diagnosed earlier
      and/or until more effective therapies are identified, comfort care alone may be a
      reasonable alternative for some of these unfortunate patients.

PMID- 15856427
TI  - Outpatient treatment of low-risk neutropenic fever in cancer patients using oral
      moxifloxacin.
AB  - BACKGROUND: Oral-based antibiotic therapy is the standard of care in the
      management of cancer patients with low-risk neutropenic fever. Nevertheless, to
      the authors' knowledge, the best antibiotic regimen and the feasibility of
      ambulatory treatment have not been clearly defined. METHODS: The authors
      evaluated the efficacy and safety of moxifloxacin as outpatient treatment in
      cancer patients with febrile neutropenia who were selected according to the
      recently proposed Multinational Association for Supportive Care in Cancer (MASCC)
      risk assessment model. Moxifloxacin was given at a dose of 400 mg orally once
      daily. RESULTS: Fifty-four patients with solid and hematologic malignancies, the
      majority of whom (84%) had advanced disease, were included in the current study.
      The median neutrophil count at the time of study entry was 340/mm3 (range, 20
      950/mm3) and the median duration of neutropenia was 4 days (range, 3-14 days). Of
      55 neutropenic episodes, 50 (91%) had a successful outcome with a median time to
      defervescence of 2 days (range, 1-5 days). A multivariate analysis indicated that
      severe neutropenia (an absolute neutrophil count of < 100 mm3) was the only
      independent factor associated with treatment failure (P < 0.04). Moxifloxacin was
      found to be well tolerated and there were no infectious deaths reported.
      CONCLUSIONS: The results of the current study demonstrated that moxifloxacin was
      a highly effective and safe regimen in the outpatient treatment of cancer
      patients with febrile neutropenia.

PMID- 15856428
TI  - Estimation of an optimal external beam radiotherapy utilization rate for head and
      neck carcinoma.
AB  - BACKGROUND: Radiotherapy is used commonly in the treatment of patients with head
      and neck carcinoma. The benchmark radiotherapy utilization rates for head and
      neck carcinoma largely are unknown. The objective of the current study was to
      determine the optimal radiotherapy utilization rate for patients with head and
      neck carcinoma and to compare this optimal rate with actual utilization rates
      where actual utilization data were available. METHODS: An optimal radiotherapy
      utilization tree was constructed that depicted all patients with head and neck
      carcinoma in whom radiotherapy was indicated according to evidence-based
      treatment guidelines. The proportions of patients with clinical attributes that
      indicated possible benefit from radiotherapy were obtained from epidemiological
      data and were inserted into the utilization tree. The optimal proportion of
      patients with carcinoma of the head and neck who should receive radiotherapy was
      calculated by merging the evidence-based recommendations with the epidemiological
      data in the tree. Optimal rates of radiotherapy utilization were compared with
      actual rates obtained from population-based studies. RESULTS: Radiotherapy was
      indicated at some point during their illness in 74% of all patients with head and
      neck carcinoma. By subsite, the optimal radiotherapy utilization rates were oral
      cavity, 74%; lip, 20%; larynx, 100%; oropharynx, 100%; salivary gland, 87%;
      hypopharynx, 100%; nasopharynx, 100%; paranasal sinuses, 100%; and unknown
      squamous cell carcinoma of the head and neck, 90%. All treatment recommendations
      were based on Level III or IV evidence. Assessment of actual radiotherapy
      utilization rates indicated an increased use of radiotherapy over time for head
      and neck carcinoma. However, there also were some decreases in the use of
      radiotherapy for some carcinoma subsites over the past 20 years, despite the
      lower actual rates compared with the optimal rates. The reasons for these
      reductions in use were not identified. CONCLUSIONS: The actual radiotherapy
      utilization rate for patients with head and neck carcinoma corresponded
      reasonably closely to the optimal rate for some populations but also identified
      some shortfalls for other patient groups. The results of this study provide a way
      of assessing shortfalls in radiotherapy.

PMID- 15856429
TI  - The prognostic value of primary tumor size in papillary and follicular thyroid
      carcinoma.
AB  - BACKGROUND: A delay in the diagnosis of differentiated thyroid carcinoma often
      leads to larger tumors, higher prevalence rates of distant metastasis, and
      earlier cause-specific deaths. Threshold tumor diameters for extrathyroidal
      growth, lymph node spread, and distant metastasis in papillary (PTC) and
      follicular thyroid carcinoma (FTC) remain to be defined. METHODS: A comparative
      correlation of primary tumor size and extrathyroidal growth, lymph node spread,
      and distant metastasis was performed for 500 institutional patients who received
      surgery for PTC or FTC. RESULTS: There were 366 patients with PTC (73.2%) and 134
      patients with FTC (26.8%). Multifocality (23.5% vs. 9.0%; P < 0.001) and lymph
      node metastasis (40.2% vs. 19.4%; P < 0.001) were more common in the patients
      with PTC than in those with FTC. Patients with FTC were older at first diagnosis
      (51.6 vs. 47.0 years; P = 0.01) compared with the patients with PTC. The FTC
      tumors were almost twice as large (39.9 vs. 20.6 mm; P < 0.001), and patients had
      a higher prevalence of distant metastasis (17.9% vs. 6.3%; P < 0.001). When
      primary tumor diameter was accounted for, cumulative risks of extrathyroidal
      growth and lymph node metastasis were higher in patients with PTC than in
      patients with FTC (P < 0.001; log-rank test). In striking contrast, the
      cumulative risk of distant metastasis was the same for PTC and FTC tumors of
      equal size (P = 0.89; log-rank test) and increased once the primary tumor size
      was > 20 mm. Pulmonary metastasis was an earlier event than bone metastasis.
      CONCLUSIONS: The data suggested that earlier intervention is warranted to keep
      suspicious thyroid nodules from growing > 20 mm (or greater than T1) and
      spreading to distant organs.

PMID- 15856430
TI  - Polymorphisms in CYP1A1 and breast carcinoma risk in a population-based case
      control study of Chinese women.
AB  - BACKGROUND: Cytochrome P450 1A1 (CYP1A1) is involved in the 2-hydroxylation of
      estrogen, the hormone that plays a critical role in the etiology of breast
      carcinoma. METHODS: The authors evaluated common polymorphisms in the CYP1A1 gene
      in relation to breast carcinoma risk in a large population-based case-control
      study among Chinese women, the Shanghai Breast Cancer Study. Because the CYP1A1*3
      and CYP1A1*4 alleles were not detected in the study population, analyses were
      performed for CYP1A1*2A (T-->C transition in the 3' noncoding region) and
      CYP1A1*2C (A-->G transition in exon 7, resulting in a substitution of Val for
      Ile) in 1134 patients with breast carcinoma and 1227 controls. RESULTS: The
      frequencies of the variant allele were 38.3% and 38.8% among cases and controls
      (P = 0.91), respectively, for the CYP1A1*2A polymorphism, and 23.1% and 24.8% (P
      = 0.26) for the CYP1A1*2C polymorphism. Homozygosity for both variant alleles in
      these 2 polymorphic sites (CYP1A1*2B) was associated with a borderline
      significant odds ratio (OR) of 0.71 (95% confidence interval [CI], 0.47-1.06).
      The reduced risk was more pronounced among postmenopausal women with long
      duration (> 30 yrs) of menstruation (OR = 0.43; 95% CI, 0.19-0.99) or among women
      with a low waist-to-hip ratio (OR = 0.52; 95% CI, 0.28-0.94). CONCLUSIONS:
      Results from the current study suggest that homozygosity for the CYP1A1*2A and
      CYP1A1*2C alleles in the CYP1A1 gene may be associated with a reduced risk for
      breast carcinoma, particularly among lean women with long-term endogenous
      estrogen exposure.

PMID- 15856431
TI  - Paclitaxel, carboplatin, and gemcitabine in the treatment of patients with
      advanced transitional cell carcinoma of the urothelium.
AB  - BACKGROUND: The objective of the current study was to evaluate the efficacy and
      toxicity of combination chemotherapy with paclitaxel, carboplatin, and
      gemcitabine in patients with advanced urothelial carcinoma. METHODS: Patients
      with metastatic or locally unresectable transitional cell carcinoma of the
      urothelium who had received either no or one previous systemic chemotherapy
      regimen were eligible. All patients received chemotherapy with intravenous
      paclitaxel at a dose of 200 mg/m(2) on Day 1, intravenous carboplatin at an area
      under the serum concentration-time curve of 5.0 on Day 1, and intravenous
      gemcitabine at a dose of 1000 mg/m(2) on Days 1 and 8. Treatment courses were
      repeated every 21 days. Patients were evaluated for response after they completed
      two treatment courses; patients who achieved an objective response and stable
      disease continued treatment for a total of six courses or until tumor
      progression. RESULTS: Sixty patients were treated between January 2000 and
      September 2003. Thirty-five patients (58%) had > or = 1 visceral sites of
      metastases, and only 4 patients (7%) had received any previous systemic
      chemotherapy. Twenty-six patients (43%) had achieved objective responses to
      treatment (12% complete responses). The median actuarial survival was 11 months,
      and the actuarial 1-year and 2-year survival rates were 46% and 27%,
      respectively. Myelosuppression was the most frequent toxicity, and Grade 3-4
      neutropenia (using the National Cancer Institute Common Toxicity Criteria
      [version 2.0]) occurred in 72% of patients (46% of courses). Ten patients were
      hospitalized for the treatment of neutropenia and fever, and 1 patient died of
      treatment-related causes. Nonhematologic toxicities were relatively uncommon.
      CONCLUSIONS: The combination of paclitaxel, carboplatin, and gemcitabine was an
      active and tolerable regimen for patients with advanced urothelial carcinoma.
      However, the regimen was more toxic and showed no obvious incremental increase in
      efficacy compared retrospectively with various two-drug regimens.

PMID- 15856432
TI  - Protein fishing with chiral molecular baits.
AB  - Chirality plays a central role in various biological recognition processes. Here
      a methodology was developed to utilize chiral recognition processes for the
      selective biotinylation of proteins in crude cell lysates. Two pairs of
      diastereomeric probes containing benzophenone and biotin were prepared through
      solid-phase synthesis. Protein-binding selectivity of each probe was examined by
      photo-cross-linking of cell lysates, followed by SDS-PAGE and Western blot. The
      study revealed that our approach permits selective labeling of benzophenone
      binding proteins in complex proteomes. In addition, it was found that the
      selectivity depends largely on a single chiral center and substitutions in the
      vicinity of benzophenone. Taken together, the current work demonstrates that
      chiral recognition process can be employed to selectively label proteins in
      complex proteomes. Thus the study opens up the possibility to expand the scope of
      chemical proteomics research for various applications, including biomarker
      discovery, drug screening and development.

PMID- 15856434
TI  - Exciton chirality in trans-1,2-diamidocyclohexanes: fluorescent chromophores.
AB  - N,N'-Carbonyl-bridged dipyrrinones constitute a new class of highly fluorescent
      chromophores suitable for investigations of stereochemistry and absolute
      configuration. Xanthoglow (N,N'-carbonylxanthobilirubic acid) diamides of trans
      1,2-diaminocyclohexane are strongly fluorescent (phiF=0.37, lambdaem=500 nm,
      lambdaex=419 nm in CHCl3) but exhibit only weak exciton circular dichroism (CD).
      In contrast, the diamide of (1R,2R)-diaminocyclohexane from the xanthoglow
      analogue whose propionic acid has been replaced by benzoic acid (N,N'-carbonyl-8
      (4-carboxyphenyl)-3-ethyl-2,7,9-trimethyl-(10H)-dipyrrin-1-one) exhibits even
      stronger fluorescence (phiF=0.62, lambdaem=495 nm, lambdaex=422 nm in CHCl3) and
      UV-visible absorption (epsilon=41,600 dm3.mol-1.cm-1 at 424 nm) in organic
      solvents. Its exciton CD (Deltaepsilon=-13 dm3.mol-1.cm-1, lambda=432 nm;
      Deltaepsilon=+2 dm3.mol-1.cm-1, lambda=382 nm) correlates with the exciton
      chirality rule.

PMID- 15856433
TI  - Effect of clarithromycin on the enantioselective disposition of lansoprazole in
      relation to CYP2C19 genotypes.
AB  - The aim of this study was to examine the effect of clarithromycin, a CYP3A4
      inhibitor, on the enantioselective disposition of lansoprazole among three
      different CYP2C19 genotype groups in healthy Japanese subjects. These subjects
      included 6 each of homozygous extensive metabolizers (homEMs), heterozygous
      extensive metabolizers (hetEMs), and poor metabolizers (PMs). In the EMs of
      CYP2C19, clarithromycin markedly increased Cmax and the AUC0-infinity of (S)
      lansoprazole and (S)-hydroxylansoprazole compared with those of the corresponding
      (R)-enantiomers. Clarithromycin significantly increased Cmax and the AUC0
      infinity of (S)-lansoprazole in the homEMs by 110% and 115%, respectively, and in
      the hetEMs by 105% and 103%, respectively, compared with placebo. Furthermore,
      clarithromycin slightly prolonged the elimination half-life of (R)-lansoprazole
      in the homEMs and hetEMs but did not alter that of (S)-lansoprazole. In the of
      PMs CYP2C19, clarithromycin significantly increased Cmax and the AUC0-infinity
      and significantly prolonged the elimination half-lives of (R)- and (S)
      lansoprazole by 51% and 49%, respectively. The present study suggests that there
      are significant drug interactions between (R)- or (S)-lansoprazole and
      clarithromycin in EMs by inhibiting the CYP3A4-catalyzed sulfoxidation primarily
      during the first pass, whereas in PMs, the overall metabolism of lansoprazole is
      inhibited.

PMID- 15856435
TI  - Absolute stereochemistry assignment of N-phosphorylimine-derived aza-Diels-Alder
      adducts with TDDFT CD calculations.
AB  - N-phosphorylimines undergo Lewis acid-catalyzed Diels-Alder reactions with
      Danishefsky's diene. Application of the chiral catalyst zinc(II)-(S)-BINOL
      results in good-to-low asymmetric induction but poor chemical conversion.
      However, the absolute stereochemistry of novel aza-Diels-Alder cycloadducts, such
      as diethyl 4-oxo-2-phenyl-3,4-dihydropyridin-1(2H)-ylphosphonate, can be
      determined using circular dichroism (CD). Comparison between experimental and
      TDDFT-calculated CD spectrum shows that use of the (S)-catalyst results in
      predominant formation of the (6R) cycloadducts.

PMID- 15856436
TI  - The Assessment of Preterm Infants' Behavior (APIB): furthering the understanding
      and measurement of neurodevelopmental competence in preterm and full-term
      infants.
AB  - The Assessment of Preterm Infants' Behavior (APIB) is a newborn neurobehavioral
      assessment appropriate for preterm, at risk, and full-term newborns, from birth
      to 1 month after expected due date. The APIB is based in ethological-evolutionary
      thought and focuses on the assessment of mutually interacting behavioral
      subsystems in simultaneous interaction with the environment. The subsystems of
      functioning assessed include the autonomic (respiration, digestion, color), motor
      (tone, movement, postures), state organization (range, robustness, transition
      patterns), attention (robustness, transitions), and self-regulation (effort,
      success) systems as well as the degree of facilitation required to support
      reorganization and subsystem balance. The environment is represented by a
      sequence of distal, proximal, tactile, and vestibular challenges, derived from
      the BNBAS. The APIB conceptualizes infant competence as the degree of
      differentiation of subsystem function and degree of modulation of subsystem
      balance at any stage in infant development. Infants are understood as actively
      seeking their next differentiation, while counting on good enough environments to
      assure progressing developmental competence. In the case of interference such as
      premature birth, the mismatch of expectation and actual experience causes
      misalignment, which may become developmentally costly. The assessment is a finely
      tuned dialogue between examiner and infant, which requires training, skill and
      self-knowledge. The APIB has well established inter-rater-reliability, concurrent
      and construct validity, and is clinically relevant for behavioral intervention
      and individually appropriate and supportive care.

PMID- 15856437
TI  - Towards creation of a unified view of the neurodevelopment of the infant.
AB  - During the twentieth century, study of the neurologic development of the fetus
      and infant has resulted in multiple neurodevelopmental assessments. They have
      been used both for determination of the integrity of the neonate as well as for
      assessment of the child's outcome from prenatal and neonatal medical
      interventions. These models of assessment have broadened our view and
      understanding of the development of functions such as movement, posture,
      attention, oromotor skills, and behavior. The link between these areas and the
      traditional areas of neurologic and psychiatric examination of older children and
      adults is explored through discussion of the maturation of movement, cranial
      nerve function, sensory, cognitive, and behavioral responses. Gaps in knowledge
      remain about the relationship between early neurodevelopmental assessments and
      later findings. A single unified means of examining the infant is also lacking.

PMID- 15856438
TI  - Assessment of infant oral sensorimotor and swallowing function.
AB  - The development of feeding and swallowing is the result of a complex interface
      between the developing nervous system, various physiological systems, and the
      environment. The purpose of this article is to review the neurobiology,
      development, and assessment of feeding and swallowing during early infancy. In
      recent years, there have been exciting advances in our understanding of the
      physiology and neurological control of feeding and swallowing. These advances may
      prove useful in furthering our understanding of the pathophysiology of dysphagia
      in infancy. Progress in developing standardized, reliable, and valid measures of
      oral sensorimotor and swallowing function in infancy has been slow. However,
      there have been significant advances in the instrumental analysis of feeding and
      swallowing disorders in infancy, including manometric analyses of sucking and
      swallowing, measures of respiration during feeding, videofluoroscopic swallow
      evaluations, ultrasonography, and flexible endoscopic examination of swallowing.
      Further efforts are needed to develop clinical evaluative measures of dysphagia
      in infancy.

PMID- 15856439
TI  - Assessment of infant cry: acoustic cry analysis and parental perception.
AB  - Infant crying signals distress to potential caretakers who can alleviate the
      aversive conditions that gave rise to the cry. The cry signal results from
      coordination among several brain regions that control respiration and vocal cord
      vibration from which the cry sounds are produced. Previous work has shown a
      relationship between acoustic characteristics of the cry and diagnoses related to
      neurological damage, SIDS, prematurity, medical conditions, and substance
      exposure during pregnancy. Thus, assessment of infant cry provides a window into
      the neurological and medical status of the infant. Assessment of infant cry is
      brief and noninvasive and requires recording equipment and a standardized
      stimulus to elicit a pain cry. The typical protocol involves 30 seconds of crying
      from a single application of the stimulus. The recorded cry is submitted to an
      automated computer analysis system that digitizes the cry and either presents a
      digital spectrogram of the cry or calculates measures of cry characteristics. The
      most common interpretation of cry measures is based on deviations from typical
      cry characteristics. Another approach evaluates the pattern across cry
      characteristics suggesting arousal or under-arousal or difficult temperament.
      Infants with abnormal cries should be referred for a full neurological
      evaluation. The second function of crying--to elicit caretaking--involves parent
      perception of the infant's needs. Typically, parents are sensitive to deviations
      in cry characteristics, but their perception can be altered by factors in
      themselves (e.g., depression) or in the context (e.g., culture). The potential
      for cry assessment is largely untapped. Infant crying and parental response is
      the first language of the new dyadic relationship. Deviations in the signal
      and/or misunderstanding the message can compromise infant care, parental
      effectiveness, and undermine the budding relationship. (c) 2005 Wiley-Liss, Inc.
      MRDD Research Reviews 2005;11:83-93.

PMID- 15856440
TI  - Prechtl's assessment of general movements: a diagnostic tool for the functional
      assessment of the young nervous system.
AB  - General movements (GMs) are part of the spontaneous movement repertoire and are
      present from early fetal life onwards until the end of the first half a year of
      life. GMs are complex, occur frequently, and last long enough to be observed
      properly. They involve the whole body in a variable sequence of arm, leg, neck,
      and trunk movements. They wax and wane in intensity, force and speed, and they
      have a gradual beginning and end. Rotations along the axis of the limbs and
      slight changes in the direction of movements make them fluent and elegant and
      create the impression of complexity and variability. If the nervous system is
      impaired, GMs loose their complex and variable character and become monotonous
      and poor. Two specific abnormal GM patterns reliably predict later cerebral
      palsy: 1) a persistent pattern of cramped-synchronized GMs. The movements appear
      rigid and lack the normal smooth and fluent character. Limb and trunk muscles
      contract and relax almost simultaneously. 2) The absence of GMs of fidgety
      character. So-called fidgety movements are small movements of moderate speed with
      variable acceleration of neck, trunk, and limbs in all directions. Normally, they
      are the predominant movement pattern in an awake infant at 3 to 5 months. Beside
      a sensitivity and specificity of 95% each, the assessment of GMs is quick,
      noninvasive, even nonintrusive, and cost-effective compared with other
      techniques, e.g., magnetic resonance imaging, brain ultrasound, and traditional
      neurological examination.

PMID- 15856441
TI  - A comparison of developmental assessments of the newborn and young infant.
AB  - Neonatal neurobehavioral assessments describe a newborn's spontaneous behavioural
      repertoire and observable responses to environmental stimuli. Infant
      developmental assessments document the range of developmental skills that emerge
      and develop over the first years of life. This review highlights two neonatal
      assessments (Einstein Neonatal Neurobehavioral Assessment Scale, Neurobehavioral
      Assessment of the Preterm Infant) and two infant assessments (Alberta Infant
      Motor Scale, Test of Infant Motor Performance). A general description of these
      tests is followed by their content and psychometric properties. These
      standardized tests of neurologic integrity are useful in characterizing current
      developmental status and in monitoring change in performance over time.

PMID- 15856442
TI  - The Amiel-Tison Neurological Assessment at Term: conceptual and methodological
      continuity in the course of follow-up.
AB  - The Amiel-Tison Neurological Assessment at Term (ATNAT) is part of a set of three
      different instruments based on a neuro-maturative framework. By sharing a same
      methodology and a similar scoring system, the use of these three assessments
      prevents any rupture in the course of high risk children follow-up from 32 weeks
      post-conception to 6 years of age. The ATNAT which takes 5 minutes to administer
      may be used in clinical setting as well as in research. Clustering of severe to
      mild neuro-cranial signs in the neonatal period permits identification of
      children who could benefit from early intervention.

PMID- 15856443
TI  - The Dubowitz neurological examination of the full-term newborn.
AB  - In an ideal world, each neonate should have a comprehensive neurological
      examination but in practice this is often difficult. In this review we will
      describe what a routine neurological evaluation in the full-term neonate should
      consist of and how the Dubowitz examination is performed. The examination has
      been used for over 20 years and can be easily performed in a short time as the
      recording sheet provides simple instructions together with simple diagrams to
      make the recording and the scoring easier. We will also indicate how the
      examination can be used to identify infants with neurological abnormalities,
      describing clinical signs which can help to differentiate infants with peripheral
      neuromuscular disorders from those with central nervous system involvement. The
      correlation between clinical and imaging findings in infants with neonatal brain
      lesions will also be reported. Finally we will briefly describe how and when to
      apply an optimality scoring system in a research setting.

PMID- 15856444
TI  - Neurobehavioral assessment from fetus to infant: the NICU Network Neurobehavioral
      Scale and the Fetal Neurobehavior Coding Scale.
AB  - This review provides an overview and definition of the concept of neurobehavior
      in human development. Two neurobehavioral assessments used by the authors in
      current fetal and infant research are discussed: the NICU Network Neurobehavioral
      Assessment Scale and the Fetal Neurobehavior Coding System. This review will
      present how the two assessments attempt to measure similar processes from pre to
      post-natal life by examining three main components of neurobehavior:
      neurological, behavioral and stress/reactivity measures. Assessment descriptions,
      strengths and weaknesses, as well as cautions and limitations are provided.

PMID- 15856445
TI  - Assessment of gestational age and neuromaturation.
AB  - Neuromaturation is the functional development of the central nervous system
      (CNS). It is by its very nature a dynamic process, a continuous interaction
      between the genome and first the intrauterine environment, then the extrauterine
      environment. Understanding neuromaturation and being able to measure it is
      fundamental to infant neurodevelopmental assessment. Fetal and preterm
      neuromaturation has become easier to observe with the advent of prenatal
      ultrasonography and neonatal intensive care units. A number of measures of degree
      of fetal maturation have been developed and used to estimate gestational age (GA)
      at birth. The most reliable measures of GA are prenatal measures, especially from
      the first trimester. Postnatal GA measurements tend to be least accurate at the
      extremes of gestation, that is, in extremely preterm and post-term infants.
      Observations of measures of neuromaturation in infants born to mothers with
      pregnancy complications, including intrauterine growth restriction, multiple
      gestation, and chronic hypertension, have led to the discovery that stressed
      pregnancies may accelerate fetal pulmonary and CNS maturation. This acceleration
      of neuromaturation does not occur before 30 weeks' gestation and has a cost with
      respect to cognitive limitations manifested in childhood. The ability to measure
      fetal and preterm neuromaturation provides an assessment of neurodevelopmental
      progress that can be used to reassure parents or identify at risk infants who
      would benefit from limited comprehensive follow-up and early intervention
      services. In addition, measures of neuromaturation have the potential to provide
      insight into mechanisms of CNS injury and recovery, much-needed early feedback in
      intervention or treatment trials and a measure of early CNS function for research
      into the relationships between CNS structure and function.

PMID- 15856446
TI  - Why assess motor functions "early and often?".

PMID- 15856447
TI  - Neurobehavioral assessment before birth.
AB  - The complexities of neurobehavioral assessment of the fetus, which can be neither
      directly viewed nor manipulated, cannot be understated. Impetus to develop
      methods for measuring fetal neurobehavioral development has been provided by the
      recognition that individual differences in neurobehavioral functioning do not
      originate with birth and acceptance of the key contribution of the antenatal
      period to postnatal life. Research has centered around four aspects of fetal
      functioning: heart rate, motor activity, behavioral state, and responsivity to
      stimulation. Longitudinal studies have revealed that the developmental
      trajectories of these characteristics parallel the developing nervous system,
      detected a transitional period between 28 and 32 weeks gestation, and established
      within-fetal stability during the second half of gestation. Despite the promise
      of fetal stimulation and habituation paradigms as measures of neural functioning,
      significant safety and ethical concerns exist. Construction of a unified fetal
      neurobehavioral scale is premature until a sufficient degree of normative data is
      available and the predictive validity of specific aspects of fetal neurobehavior
      to child developmental outcomes is better established.

PMID- 15856449
TI  - Introduction: developmental assessment of the fetus and young infant.

PMID- 15856450
TI  - DNA adduct formation by the environmental contaminant 3-nitrobenzanthrone after
      intratracheal instillation in rats.
AB  - 3-Nitrobenzanthrone (3-NBA) is an environmental pollutant and suspected human
      carcinogen found in emissions from diesel and gasoline engines and on the surface
      of ambient air particulate matter; human exposure to 3-NBA is likely to occur
      primarily via the respiratory tract. In our study female Sprague Dawley rats were
      treated by intratracheal instillation with a single dose of 0.2 or 2 mg/kg body
      weight of 3-NBA. Using the butanol enrichment version of the (32)P-postlabeling
      method, DNA adduct formation by 3-NBA 48 hr after intratracheal administration in
      different organs (lung, pancreas, kidney, urinary bladder, heart, small intestine
      and liver) and in blood was investigated. The same adduct pattern consisting of
      up to 5 DNA adduct spots was detected by thin layer chromatography in all tissues
      and blood and at both doses. Highest total adduct levels were found in lung and
      pancreas (350 +/- 139 and 620 +/- 370 adducts per 10(8) nucleotides for the high
      dose and 39 +/- 18 and 55 +/- 34 adducts per 10(8) nucleotides for the low dose,
      respectively) followed by kidney, urinary bladder, heart, small intestine and
      liver. Adduct levels were dose-dependent in all organs (approximately 10-fold
      difference between doses). It was demonstrated by high performance liquid
      chromatography (HPLC) that all 5 3-NBA-derived DNA adducts formed in rats after
      intratracheal instillation are identical to those formed by other routes of
      application and are, as previously shown, formed from reductive metabolites bound
      to purine bases. Although total adduct levels in the blood were much lower (41 +/
      27 and 9.5 +/- 1.9 adducts per 10(8) nucleotides for the high and low dose,
      respectively) than those found in the lung, they were related to dose and to the
      levels found in lung. These results show that uptake of 3-NBA by the lung induces
      high levels of specific DNA adducts in several organs of the rat and an identical
      adduct pattern in DNA from blood. Therefore, 3-NBA-DNA adducts present in the
      blood are useful biomarkers for exposure to 3-NBA and may help to assess the
      effective biological dose in humans exposed to it.

PMID- 15856452
TI  - A high-fat diet generates alterations in nuclear receptor expression: prevention
      by vitamin A and links with cyclooxygenase-2 and beta-catenin.
AB  - Epidemiologic studies suggest that intake of high energy from fat, inducing
      overweight, increases the risk of cancer development and promotes colon
      carcinogenesis. It is therefore important to understand which parameters are
      affected early on by a high-fat diet in order to devise and improve protective
      nutritional strategies. We investigated the effect of high energy/fat intake on
      colon mucosa of male Wistar rats induced by a single 1,2-dimethylhydrazine (DMH)
      injection. Aberrant crypt foci (ACF) were numbered and modifications in
      cyclooxygenase-2 (COX-2) and beta-catenin levels assessed. Peroxisome
      proliferator- and retinoic acid-activated receptors (PPAR and RAR, RXR) are key
      transcription factors regulating gene expression in response to nutrient
      activated signals. A short-term study was designed to evaluate whether
      alterations in mRNA expression of nuclear receptors can be detected at the
      beginning of the weight gain phase induced by an appetizing hyperlipidic diet
      (HLD). HLD consumption induced early downregulation of PPARgamma (-33.1%) and
      RARbeta (-53.1%) mRNA expression concomitant with an increase in levels of COX-2
      (+45.5%) and beta-catenin (+84.56%) and in the number of ACF (191.56 +/- 88.60
      vs. 21.14 +/- 11.64, p < 0.05). These findings suggest that HLD increases ACF
      occurrence, possibly through alterations in the mRNA expression profile of
      nuclear receptors. Moreover, the use HLD rich in retinyl esters or supplemented
      with all-trans retinoic acid led to a reduction in the number of ACF. Vitamin A
      also prevented HLD-induced alterations and the increase in levels of COX-2 and
      beta-catenin. The present observations show a protective role for vitamin A
      against disturbances associated with HLD exposure in induced colon
      carcinogenesis.

PMID- 15856451
TI  - Green tea drinking and multigenetic index on the risk of stomach cancer in a
      Chinese population.
AB  - The purpose of our study was to examine the roles of green tea drinking, other
      risk and protective factors, and polymorphism of susceptibility genes such as
      GSTM1, GSTT1, GSTP1, and p53 codon 72 and their possible joint effects on the
      risk of stomach cancer. A population-based case-control study was conducted in
      Taixing, China, including 206 newly diagnosed cases with stomach cancer and 415
      healthy control subjects. Epidemiological data were collected by in-person
      interviews using a standard questionnaire. Polymorphisms of susceptibility genes
      were assayed by PCR-RFLP techniques. A multigenetic index was created by summing
      up the number of risk genotypes. The data were analyzed using the logistic
      regression model. A reverse association between green tea drinking and risk of
      stomach cancer was observed with an adjusted odds ratio (OR) of 0.59 (95%
      confidence interval [CI] = 0.34-1.01). Dose-response relationship was shown (p
      trend < 0.05). A higher score on the multigenetic index was associated with
      increased risk of stomach cancer with an adjusted OR of 2.21 (95% CI = 1.02-4.79)
      for those with at least 3 risk genotypes compared to those with <2 risk
      genotypes. Green tea drinking was suggested to have more than multiplicative
      interactions with alcohol consumption with an adjusted OR for interaction of 4.57
      (95% CI = 1.62-12.89), and with higher multigenetic index with adjusted OR for
      interaction of 2.31 (95% CI = 0.88-6.03). The protective effect of green tea
      drinking was observed on the risk of stomach cancer and the possible effect
      modification by susceptibility genes was suggested.

PMID- 15856454
TI  - Prognostic role of cyclooxygenase-2 in neoadjuvant-treated patients with squamous
      cell carcinoma of the esophagus.
AB  - Based on our previous demonstration that elevated cyclooxygenase-2 (COX-2)
      expression is a prognostic factor for reduced survival in patients with
      adenocarcinoma of the esophagus, the aim of our study was to analyze the role of
      COX-2 expression in esophageal squamous cell carcinoma. We analyzed COX-2 protein
      expression from 117 consecutive patients by immunohistochemistry using a COX-2
      specific monoclonal antibody. Eighty-one patients had not received any therapy
      before surgery whereas 36 patients received neoadjuvant chemotherapy as part of a
      randomized controlled trial. In the patients who received no chemotherapy, COX-2
      expression was low in 75% and high in 25% of the specimens. In this patient
      group, high COX-2 expression associated with distal location of the tumor (p =
      0.02), but did not correlate with any other clinicopathological parameter tested,
      including overall survival. In the patient group who received neoadjuvant
      chemotherapy, postoperative COX-2 expression was low in 69% and high in 31%.
      Interestingly, in this patient group low COX-2 expression correlated with
      development of distant metastases (p = 0.03) and to reduced overall survival (p =
      0.02). Our results show that the prognostic significance of COX-2 depends on the
      histological type of esophageal carcinoma and preoperative treatment of the
      patient. In conclusion, COX-2 is not a prognostic marker in squamous cell
      carcinoma of the esophagus, but low COX-2 expression is associated with poor
      prognosis in the neoadjuvant-treated patients.

PMID- 15856455
TI  - Selective infiltration of CCR5(+)CXCR3(+) T lymphocytes in human colorectal
      carcinoma.
AB  - T cell infiltration in colorectal cancer is associated with a favorable
      prognosis, suggesting an occurrence of a certain degree of anti-tumor immunity. T
      helper type 1 (Th1) and Th2 cells are now known to selectively express CC
      chemokine receptor 5 (CCR5)/CXC-chemokine receptor 3 (CXCR3) and CCR4,
      respectively. To clarify the mechanism of T cell infiltration, we examined in
      situ expression of these chemokine receptors and their respective chemokine
      ligands in 40 cases of human colorectal cancer. Immunohistochemistry showed a
      predominant accumulation of T cells expressing CCR5 and CXCR3 mainly along the
      invasive margin, whereas those expressing CCR4 were rare. Flow cytometric
      analysis showed that more than half of CD8(+) T cells and a fraction of CD4(+)
      cells isolated from fresh tumor tissues co-expressed CCR5 and CXCR3, and CD8(+) T
      cells and CD4(+) cells predominantly produced interferon-gamma (IFN-gamma) over
      interleukin-4 (IL-4) after in vitro stimulation. RANTES/CCL5, a ligand of CCR5,
      was localized within infiltrating CD8(+) T cells in a granular pattern, whereas
      IP-10/CXCL10, a ligand of CXCR3, was localized in cancer cells and macrophages
      along the invasive margin. These data were consistent with an active recruitment
      of T cells expressing CCR5 or CXCR3 into the invasive margin of colorectal
      cancer. With the previous clinicopathological studies showing a favorable
      prognostic impact of T cell infiltration in colorectal cancer, our study supports
      the occurrence of a certain level of Th1-shifted cellular immune responses in
      human colorectal cancer.

PMID- 15856456
TI  - Tumor-specific changes in mtDNA content in human cancer.
AB  - Mitochondrial DNA (mtDNA) alterations are associated with various cancer types,
      suggesting that the mitochondrial genome may be a critical contributing factor in
      carcinogenesis. mtDNA alterations have been suggested as a potentially sensitive
      and specific biomarker for several cancer types. We examined mtDNA content in 25
      pairs of normal and tumor breast tissue samples, 37 papillary thyroid carcinoma
      (PTC), 21 benign thyroid neoplasms and in 20 paired normal and PTC samples. Our
      results showed that mtDNA content was reduced in 80% of the breast tumors
      relative to their corresponding normal. mtDNA was increased in papillary thyroid
      carcinomas, however, when compared to the corresponding normal DNA taken from the
      same individual. Also, mtDNA content was increased in none-paired PTC samples
      compared to the normal controls. Our findings indicate that changes in mtDNA
      content during carcinogenesis may be regulated in a tumor specific manner.
      Additionally, changes in mtDNA levels did not correlate with tumor grade and
      metastasis, suggesting that these alterations may occur in the early stages of
      tumorigenesis. Our findings suggest that mtDNA content can be used as a molecular
      diagnostic tool to help identify genetic abnormalities in human tumors.

PMID- 15856457
TI  - Escape from microenvironmental control and progression of intraepithelial
      neoplasia.
AB  - We previously reported that normal human keratinocytes controlled neoplastic
      progression of tumor cells at an early stage of transformation in stratified
      squamous epithelium. We now studied if cells at a more advanced stage of
      transformation were also subject to such microenvironmental control. To
      accomplish this, 3D human tissues that mimic intraepithelial neoplasia were
      fabricated by mixing genetically marked (beta-gal), early-stage (II-4 cells) or
      advanced-stage (SCC13) transformed keratinocytes with normal keratinocytes, and
      tumor cell fate and phenotype were monitored in organotypic culture and after
      surface transplantation to nude mice. In vivo, SCC13 cells evaded local growth
      suppression to undergo connective tissue invasion at significantly lower tumor
      cell volumes (12:1, 50:1 normal:tumor cells) than II-4 cells. This behavior was
      explained by the growth suppression of II-4 cells, while advanced-stage tumor
      cells escaped this control and continued to undergo clonal expansion in mixed
      cultures to form large, intraepithelial tumor clusters. These communities of
      tumor cells underwent autonomous growth that was associated with altered
      expression of markers of differentiation (keratin 1) and cell-cell communication
      (connexin-43). Furthermore, significantly greater numbers of SCC13 cells expanded
      into a basal position after low-calcium stripping of suprabasal cells of mixed
      cultures compared to II-4 cells, suggesting that expansion of these cells enabled
      tumor cell invasion after transplantation. These findings demonstrated that early
      tumor development in human stratified squamous epithelium required escape from
      microenvironmental growth control that was dependent on the transformation stage
      of intraepithelial tumor cells during the premalignant stage of cancer
      progression.

PMID- 15856458
TI  - Melanoma patients respond to a new HLA-A*01-presented antigenic ligand derived
      from a multi-epitope region of melanoma antigen TRP-2.
AB  - Tyrosinase-related protein-2 (TRP-2) is a known target antigen of spontaneous
      cytotoxic T cell responses in melanoma patients. Its frequent expression in
      metastatic tumors suggests that it might be an ideal candidate antigen for T cell
      based immunotherapy. To provide knowledge about TRP-2-derived T cell epitopes
      useful for immunotherapy we applied a "reverse immunology strategy" based on
      repeated in vitro peptide stimulation of peripheral blood lymphocytes (PBL) from
      normal donors with predicted HLA-A*01 ligands. This led to the identification of
      TRP-2(181-190) as the first HLA-A*01-presented TRP-2-derived epitope. T-cell
      lines specific for peptide TRP-2(181-190) could be established from PBL of 50% of
      the normal HLA-A*01(+) donors tested. Such T cells responded specifically to
      autologous dendritic cells transduced virally with TRP-2, as well as to HLA
      A*01(+), TRP-2(+) melanoma cells, although tumor cells had to be pretreated with
      IFN-gamma to become susceptible to T cell recognition. Interestingly, short-term
      in vitro peptide stimulation of PBL from HLA-A*01(+) melanoma patients showed the
      presence of TRP-2(181-190)-reactive CD8(+) T cells in some donors, suggesting
      their in vivo sensitization. Because TRP-2(181-190) overlaps with the known HLA
      A*0201-presented epitope TRP-2(180-188), an 11mer peptide encompassing both
      epitopes might be of specific value for vaccination of a broad population of
      melanoma patients.

PMID- 15856459
TI  - Breast cancer in HRT users.

PMID- 15856460
TI  - Blood sampling as critical preanalytical determinant to use circulating MMP and
      TIMP as surrogate markers for pathological processes.

PMID- 15856462
TI  - Immune responses to DNA mismatch repair enzymes hMSH2 and hPMS1 in patients with
      pancreatic cancer, dermatomyositis and polymyositis.
AB  - To identify tumor antigens useful for diagnosis and immunotherapy of patients
      with pancreatic ductal adenocarcinoma, we applied a SEREX approach with a cDNA
      library made from 5 pancreatic cancer cell lines and sera obtained from 8
      patients with pancreatic cancer, and isolated total 32 genes, including 14
      previously characterized genes and 18 genes with unknown functions. Among these
      isolated antigens, serum IgG antibodies for 2 isolated DNA mismatch repair
      enzymes, Homo sapiens mutS homolog 2 (hMSH2) and Homo sapiens postmeiotic
      segregation increased 1 (hPMS1), were detected in patients with pancreatic ductal
      adenocarcinoma and dermatomyositis (DM), and polymyositis (PM), but not in sera
      from healthy individuals. Immunohistochemical study demonstrated that hMSH2 and
      hPMS1 were over-expressed in pancreatic ductal adenocarcinoma compared to normal
      pancreatic ducts. These results suggested that hMSH2 and hPMS1 may be useful as
      CD4+ helper T cell antigens for immunotherapy of pancreatic cancer patients and
      that serum IgG antibodies may be useful for diagnosis of patients with pancreatic
      ductal adenocarcinoma and DM/PM.

PMID- 15856463
TI  - Association of estrogen receptor alpha polymorphisms with breast cancer risk in
      older Caucasian women.
AB  - Estrogens exert their effect on the breast through the estrogen receptor. We
      prospectively investigated breast cancer risk associated with 2 polymorphic sites
      in the estrogen receptor alpha gene (ESR1). A total of 4,248 Caucasian women from
      the Study of Osteoporotic Fractures were genotyped for the -401 T/C and -354 A/G
      polymorphisms in ESR1. Cox proportional hazards models were used to estimate
      hazard ratios (HR) and 95% confidence intervals (CI) for the associations between
      genotypes and breast cancer. During a mean follow-up of 12.4 years, 252 (5.9%)
      women developed breast cancer. The HR (95% CI) for breast cancer were 0.928
      (0.708, 1.22) and 0.834 (0.538, 1.29) for the -354 A/G and A/A genotypes,
      respectively. Interactions with -354 variant were observed for smoking (HR = 1.52
      and 1.56 for A/G and A/A smokers, respectively; HR = 0.74 and 0.60 for A/G and
      A/A non-smokers, respectively; interaction p = 0.03) and walking (HR = 0.75 and
      1.15 for A/G and A/A walkers, respectively; HR = 0.18 and 0.49 for A/G and A/A
      non-walkers, respectively; interaction p = 0.01). There were no differences in
      the HR for the -401 T/C genotypes. An interaction between parity and carriage of
      the T allele was found (HR = 0.60 vs. 1.12 for nulliparous vs. parous women;
      interaction p = 0.03). ESR1 polymorphisms in combination with lifestyle factors
      may be associated with breast cancer risk in older Caucasian women.

PMID- 15856464
TI  - Adam-9 expression and regulation in human skin melanoma and melanoma cell lines.
AB  - ADAM-9 belongs to a family of transmembrane disintegrin-containing
      metalloproteinases (ADAMs) involved in protein ectodomain shedding and cell-cell
      and cell-matrix interactions. However, the specific biological functions of ADAM
      9 are still unclear. The aim of this study was to analyze the expression of ADAM
      9 in melanoma in vivo and in melanoma cell lines in vitro. In melanoma ADAM-9
      protein expression appeared to be restricted to the melanoma cells within the
      invading front. Interestingly, ADAM-9 protein was detected in the melanoma cells
      and in peritumoral stromal fibroblasts, while it was absent in fibroblasts distal
      to the tumor site. RNA analysis of melanoma cell lines with different invasive
      abilities showed ADAM-9 expression in varying amounts in all cell lines,
      independent of their invasive and metastatic capacities. In MV3 melanoma cells,
      ADAM-9 expression did not depend on homotypic cell-cell contact and on cell
      matrix interaction when the cells were cultured on planar extracellular matrix
      components. However, we observed downregulation of ADAM-9 mRNA expression upon
      culture of melanoma cells within 3-dimensional lattices composed of fibrillar
      type I collagen, whereas culture within gels consisting of the polysaccharide
      alginate did not alter transcript levels. These results identified fibrillar
      collagen type I as a key factor in ADAM-9 regulation by cell-matrix interactions.
      Interestingly, we also observed a 3-fold downregulation of ADAM-9 transcript
      levels upon treatment with interleukin (IL)-1alpha, a proinflammatory cytokine
      known to induce expression of other ADAM and matrix metalloproteinase (MMP)
      family members. In summary, our data suggest a novel role of fibrillar collagen
      and of soluble factors for the regulation of ADAM-9 expression in vitro.

PMID- 15856465
TI  - Cyclooxygenase-2 overexpression in MCF-10F human breast epithelial cells inhibits
      proliferation, apoptosis and differentiation, and causes partial transformation.
AB  - To investigate the effects of cyclooxygenase-2 (COX-2) overexpression on breast
      cancer development, we stably transfected MCF-10F human breast epithelial cells
      with an expression vector containing human COX-2 cDNA oriented in the sense (10F
      S) or antisense (10F-AS) direction. As expected, 10F-S cells expressed elevated
      levels of COX-2 protein, whereas this protein was undetectable in the 10F-AS
      cells. Prostaglandin E(2) production in these cells reflected COX-2 levels. The
      10F-S cells had a significantly decreased rate of proliferation compared to 10F
      AS or parental cells, and a delay in progression through the G(1) phase of the
      cell cycle. COX-2 overexpression also caused resistance to detachment-induced
      apoptosis (anoikis) as well as an inhibition of differentiation in cells cultured
      in Matrigel. Furthermore, after approximately 20 passages in culture, 10F-S cells
      developed fibroblast-like features, expressed vimentin, and formed foci of dense
      growth when cultured at confluence, suggesting that the cells were undergoing
      epithelial to mesenchymal transition (EMT). The 10F-S cells, however, were unable
      to grow in soft agar or form tumors in nude mice, suggesting that they were only
      partially transformed. Our observations suggest that COX-2 overexpression in
      human breast epithelial cells will predispose the mammary gland to
      carcinogenesis.

PMID- 15856466
TI  - Detection of carbonic anhydrase 9-expressing tumor cells in the lymph nodes of
      vulvar carcinoma patients by RT-PCR.
AB  - Regional lymph node status is an important prognostic factor for vulvar cancer.
      The goal of our study was to elaborate a reliable test for detecting
      micrometastases, undetectable by traditional methods, in the lymph nodes of
      vulvar squamous carcinoma patients. For this purpose, carbonic anhydrase-9 (CA9)
      was investigated as a cancer-related marker by RT-PCR. Firstly, primary carcinoma
      specimens were examined for CA9 expression by immunohistochemistry with M75
      monoclonal antibody. All 19 tissues exhibited a variable degree of staining,
      which was mostly confined to the plasma membranes of tumor cells.
      Correspondingly, all primary tumor specimens and the control A-431 vulvar cancer
      cell line gave a positive signal in the nested RT-PCR assay designed to detect
      CA9-expressing cells with a high sensitivity. Analysis of 77 lymph node specimens
      from 20 patients revealed a full correlation between RT-PCR results and standard
      hematoxylin-eosin staining in 75% of samples, whereas 25% of specimens were
      negative by the standard method and positive for CA9 mRNA, accounting for 28% of
      all histologically negative lymph nodes. There were no false-negatives with RT
      PCR. A positive inguinal lymph node with a negative sentinel node was observed in
      the same groin only once in 38 specimens. Our findings clearly indicate potential
      value of CA9 as a molecular marker for the assessment of regional lymph node
      status in vulvar cancer patients and support a possible utility of our RT-PCR
      assay in the detection of micrometastases.

PMID- 15856467
TI  - Laminin 5 expression protects against anoikis at aerogenous spread and lepidic
      growth of human lung adenocarcinoma.
AB  - Adenocarcinoma of the lung is characterized by frequent aerogenous spread (AE)
      and advancement along the alveolar wall (BAC growth). To elucidate the mechanism
      of AE metastasis and BAC growth in human lung adenocarcinoma, we established an
      in vivo orthotopic animal model and an in vitro culture. Investigation of
      expression levels of integrins, laminins and Type IV collagens, which are the
      major regulating molecules for cell attachment and anoikis was carried out and a
      clear correlation between the expression level of laminin 5 (LN5) and the BAC
      growth was observed using an orthotopic animal model. Introduction of LN5 cDNA to
      A549 cells increased anoikis resistance in an expression dependent manner. Cells
      with LN5 overexpression resisted with anoikis after treatment with PI3K-Akt and
      ERK inhibitors. The amount of phosphorylated focal adhesion kinase (FAK) was also
      higher in LN5 overexpressing cells. Major tyrosine residues of the EGF receptor
      at 1068, 1086 and 1173, except at 1148, remained phosphorylated only in the LN5
      overexpressing cells even without EGF stimulation, that indicates the ligand
      independent activation of EGF receptor. BAC growth ratio and AE was confirmed to
      be significantly correlated with LN5 expression in surgically resected human lung
      adenocarcinomas by immunohistochemistry. Our results indicate that the activation
      of the EGF receptor by overexpressing LN5-integrin-FAK signaling pathway may play
      a crucial role in BAC growth and AE metastasis in human lung adenocarcinoma.

PMID- 15856468
TI  - Suppression of the TIG3 tumor suppressor gene in human ovarian carcinomas is
      mediated via mitogen-activated kinase-dependent and -independent mechanisms.
AB  - The TIG3 gene is a retinoic acid inducible class II tumor suppressor gene
      downregulated in several human tumors and malignant cell lines. Diminished TIG3
      expression correlates with decreased differentiation whereas forced expression of
      TIG3 suppresses oncogenic signaling pathways and subsequently induces
      differentiation or apoptosis in tumor cells. Analysis of TIG3 mRNA expression in
      a large set of cDNA pools derived from matched tumor and normal human tissues
      showed a significant downregulation of TIG3 in 29% of the cDNA samples obtained
      from ovarian carcinomas. Using in situ hybridization, we demonstrated expression
      of TIG3 in the epithelial lining of 7 normal ovaries but loss of TIG3 expression
      in 15/19 of human ovarian carcinoma tissues. In SKOV-3, CAOV-3 and ES-2 ovarian
      carcinoma cell lines, downregulation of TIG3 mRNA was reversible and dependent on
      an activated MEK-ERK signaling pathway. Re-expression of TIG3 mRNA in these cells
      upon specific interference with the MEK-pathway was correlated with growth
      inhibition of the cells. In OVCAR-3 and A27/80 ovarian carcinoma cells, TIG3
      suppression is MEK-ERK independent, but expression could be reconstituted upon
      interferon gamma (IFNgamma) induction. Overexpression of TIG3 in A27/80 ovarian
      carcinoma cells significantly impaired cell growth and despite increased mRNA
      levels, TIG3 protein was hardly detectable. These results suggest that TIG3 is
      negatively regulated by an activated MEK-ERK signaling pathway. Further
      mechanisms must interfere with TIG3 expression that are independent of MEK and
      partially include interferon-responsive components.

PMID- 15856470
TI  - Successful combination of local CpG-ODN and radiotherapy in malignant glioma.
AB  - Oligodeoxynucleotides containing CpG motifs (CpG-ODN) display broad
      immunostimulating activity and are currently under clinical trial in various
      malignancies, including recurrent glioblastomas. Combining CpG-ODN with another
      therapy that could induce antigen release might enhance tumor-specific immune
      response. We investigated whether radiotherapy (RT) could be associated
      advantageously to intratumoral injections of CpG-ODN. Fisher rats bearing 9L
      glioma were treated with various combinations of RT and CpG-28, an
      oligonucleotide with good immunostimulating activity. RT and CpG-28 induced
      complete tumor remission in one-third of the animals. When both treatments were
      combined, complete tumor remission was achieved in two-thirds of the animals (p <
      0.001 when compared to non-treated rats, p < 0.03 when compared to CpG-28 alone).
      Such efficacy was not observed in nude mice, underlying the role of T cells in
      antitumor effects. The combination of both treatments appeared optimal when the
      delay between RT and CpG-28 administration was <3 days (from 100% survival for a
      3 days delay, to 57% survival for a 21 days delay, p < 0.05). Tumor infiltration
      by immune cells and expression within tumors of the CpG receptor, TLR9, were not
      modified by irradiation. These results support an attractive strategy of
      sequential radiotherapy and immunotherapy by CpG-ODN and have potential
      implications for future clinical trials with CpG-ODN.

PMID- 15856471
TI  - Glucocorticoid administration in antiemetic therapy: Is it safe?

PMID- 15856472
TI  - Clinicopathological features and microsatellite instability (MSI) in colorectal
      cancers from African Americans.
AB  - African Americans (AAs) have a 1.5 times higher risk of colorectal carcinoma
      (CRC) than Caucasians. Gene silencing through CpG island hypermethylation has
      been associated with the genesis or progression of microsatellite instability
      (MSI) largely due to 1 target for hypermethylation being the DNA mismatch repair
      gene hMLH1; there is anecdotal evidence of an increased incidence of MSI among
      AAs. P16 and hMLH1 can be inactivated by hypermethylation of their respective
      promoter regions, abrogating the ability to regulate cell proliferation and
      repair processes. We studied such methylation, as well as hMHS2 expression in
      colorectal cancers from AA patients to determine if MSI is associated with
      epigenetic silencing. Experiments were conducted on matched normal and colon
      cancer tissues from AA patients (n = 51). A total of 5 microsatellite markers
      (D2S123, D5S346, D17S250, BAT25 and BAT26) were used to evaluate MSI status. P16
      and hMLH1 promoter methylation status was determined following bisulfite
      modification of DNA and using methylation specific PCR, while
      immunohistochemistry (IHC) was used to examine expression of hMLH1 and hMSH2. A
      total of 22 (43%) cancers demonstrated microsatellite instability-high (MSI-H),
      while 27 were microsatellite stable (MSS) and 2 were microsatellite instability
      low (MSH-L). Most of the MSI-H tumors were proximal, well differentiated and
      highly mucinous. Most patients in the MSI-H group were females (68%). The p16
      promoter was methylated in 19 of 47 (40%) tumors. A total of 7 of these CRCs
      demonstrated MSI-H (33%). The hMLH1 promoter was methylated in 29 of 34 (85%)
      tumors, of which 13 CRCs demonstrated MSI-H (87%). hMLH1 and hMSH2 staining was
      observed in 66% and 38% of MSI-H tumors, respectively. Overall, the prevalence of
      MSI-H colorectal tumor was 2-3-fold higher, while the defect in the percentage
      expression of mismatch repair (MMR) genes (hMLH1 and hMSH2) was similar in AA
      patients compared to the U.S. Caucasian population. Similar numbers of AA MSS
      tumors with p16 and hMLH1 methylation likely indicate hemimethylation of genes
      that might reflect environmental or genetic influences that might be more common
      in the AA population.

PMID- 15856473
TI  - Vaccination with dendritic cells pulsed with apoptotic tumors in combination with
      anti-OX40 and anti-4-1BB monoclonal antibodies induces T cell-mediated protective
      immunity in Her-2/neu transgenic mice.
AB  - Tumor cells express tumor-associated antigens (TAAs), which can serve as targets
      for the immune system. However, the majority of TAAs are overexpressed products
      of normal cellular genes; as such, self-tolerance mechanisms have hindered their
      use for the induction of effective antitumor responses. One such normal self
      protein is the growth factor receptor Her-2/neu, which is overexpressed in 25-35%
      of all mammary carcinomas in humans. In previous studies, we have demonstrated
      that Her-2/neu mice are functionally tolerant to neu antigens and contain only a
      low avidity T-cell repertoire to neu antigens. However, this residual low-avidity
      T-cell repertoire has antitumor activity. In this study, we compared the immune
      responses of Her-2/neu mice immunized with dendritic cells (DCs) pulsed with
      soluble neu protein or with apoptotic tumor cells. Analysis of the antitumor
      response shows that Her-2/neu mice vaccinated with DCs pulsed with Her-2/neu
      antigens retard tumor growth; however, vaccination with DCs pulsed with apoptotic
      tumor cells induces a stronger antitumor effect. Administration of multiple
      immunizations in combination with the costimulatory agonist anti-OX40 or anti-4
      1BB MAb significantly enhanced the immune responses in these mice, resulting in
      complete tumor rejection if the tumor burden was small and substantial tumor
      reduction with a larger tumor burden. These results have important implications
      for the design of tumor vaccination strategies, suggesting that the use of
      vaccines that stimulate a broad immune response in combination with costimulatory
      molecules as immunomodulators could significantly improve the antitumor immune
      response in tolerant hosts.

PMID- 15856474
TI  - Lymphatic and vascular embolizations are independent predictive variables of
      inguinal lymph node involvement in patients with squamous cell carcinoma of the
      penis: Gruppo Uro-Oncologico del Nord Est (Northeast Uro-Oncological Group)
      Penile Cancer data base data.
AB  - BACKGROUND: The objective of the current study was to identify independent
      clinical and pathologic variables that were predictive of lymph node involvement
      in patients with squamous cell carcinoma of the penis in a multicenter series
      with the intent to select patients who were suitable to undergo immediate
      inguinal lymphadenectomy. METHODS: Data were analyzed from 175 patients who
      underwent surgery for penile carcinoma in 11 urologic centers participating in
      the Gruppo Uro-Oncologico del Nord-Est (Northeast Uro-Oncological Group) Penile
      Cancer Data Base. Pathologically positive lymph nodes were defined as the
      presence of histologically confirmed lymph node metastasis in patients who
      underwent either immediate or delayed inguinal and/or pelvic lymphadenectomy.
      Patients who had clinically positive lymph nodes with cytologically positive fine
      needle aspiration results and who had not undergone lymphadenectomy were
      censored. RESULTS: Overall, lymph-node involvement was observed in 71 of 175
      patients (40.6%) included in the analyses. After analyzing the whole group of
      patients, the following variables were identified as independent predictors of
      pathologic lymph node metastasis: clinical lymph node status, pathologic stage of
      the primary tumor, venous and lymphatic embolizations, and histologic grade. In
      the subgroup of patients with clinically negative lymph nodes, tumor thickness,
      histologic grade, lymphatic and venous embolizations, infiltration of both corpus
      spongiosum and urethra, and pathologic stage of the primary tumor (according to
      the 1997 TNM classification system) were predictive of lymph node involvement on
      univariate analysis. The generated logistic regression model showed that venous
      and/or lymphatic embolizations and infiltration of the corpus spongiosum and/or
      urethra were independent predictors of pathologic lymph node metastasis in
      patients with clinically negative lymph nodes. CONCLUSIONS: Venous and/or
      lymphatic embolizations played relevant roles as predictors of pathologic lymph
      node involvement in patients with penile neoplasia and should be considered
      important parameters in determining which patients with clinically negative lymph
      nodes should undergo immediate lymphadenectomy.

PMID- 15856475
TI  - Phase I and initial phase II results from a trial investigating weekly docetaxel
      and carboplatin given neoadjuvantly and then concurrently with concomitant boost
      radiotherapy for locally advanced squamous cell carcinoma of the head and neck.
AB  - BACKGROUND: The current Phase I/II study assessed induction docetaxel/carboplatin
      given weekly for 4 weeks, followed by weekly docetaxel/carboplatin and
      concomitant boost radiotherapy (CB-XRT) for locally advanced head and neck
      squamous cell carcinoma. METHODS: Twenty patients with Stage III or IV (M0)
      disease of the oropharynx, supraglottic larynx, or hypopharynx were enrolled.
      Patients initially received docetaxel 20 mg/m2 and carboplatin area under the
      curve (AUC) 2 weekly x 4. Patients with stable (SD) or responding disease
      subsequently received dose-escalated docetaxel (10-20 mg/m2 in sequential patient
      cohorts) and carboplatin AUC 1 weekly x 5 with CB-XRT (1.8 gray [Gy] every day x
      15 days, followed by 1.8/1.5 Gy twice per day x 13 days). RESULTS: All patients
      were evaluable, and 15 patients (5 patients with Stage III disease, 10 patients
      with Stage IV disease) completed all planned therapy. The target docetaxel dose
      level of 20 mg/m(2) weekly with radiotherapy was achieved with no dose-limiting
      toxicities. The most frequent maximum toxicities during chemoradiotherapy were
      Grade 3 mucositis, dysphagia, and/or pain. Primary site responses after induction
      included 4 patients with partial responses, 11 patients with SD, and 5 patients
      with disease progression. Fifteen patients (75%) continued to receive
      chemoradiotherapy, with 14 patients attaining a complete response (CR). Overall,
      a clinicopathologic neck CR after chemoradiotherapy was achieved in 9 of 10
      patients. One patient had persistent primary disease and underwent salvage
      surgery, whereas another died of unrelated causes before neck assessment.
      Thirteen patients remain free of any disease event, with a median follow-up of 15
      months (range, 3-29 months). CONCLUSIONS: This regimen was feasible, safe, and
      particularly well tolerated. Early Phase II outcomes revealed promising activity
      in patients completing all treatment. Initial induction response results
      suggested that further investigation of this regimen with more aggressive
      induction therapy is warranted.

PMID- 15856476
TI  - The effect of stationary phase on lipophilicity determination of beta-blockers
      using reverse-phase chromatographic systems.
AB  - Evaluation of lipophilicity parameters for basic compounds using different
      chromatographic stationary phases is presented. An HPLC method for determination
      of lipophilic molecule-stationary phase interactions was based on gradient
      analysis. Differences in correlation between the lipophilicity of compounds and
      experimental chromatographic results obtained in pseudo-membrane systems showed a
      strong influence of stationary phase structure and physico-chemical properties.
      beta-Blocker drugs with varying lipophilicity and bio-activity were chosen as
      test compounds. The stationary phases used for the study were monolithic rod
      structure C18 and silica gel octadecyl phase SG-C18 as reference material. The
      second group was silica gel-based polar-embedded alkylamide and cholesterolic
      phases. The mobile phase was composed of acetonitrile or methanol with ammonium
      acetate, and a linear gradient of methanol and acetonitrile in mobile phase was
      performed. A linear correlation of plots of log k(g) = f(log P) was observed,
      especially for polar-embedded phases, and this allowed log P(HPLC) to be
      calculated. The behavior of stationary phases in methanol and acetonitrile buffer
      showed differences between obtained log P(HPLC) values.

PMID- 15856477
TI  - Improvement in preoperative staging of gastric adenocarcinoma with positron
      emission tomography.
AB  - BACKGROUND: Positron emission tomography (PET) with 18- fluorodeoxyglucose (FDG)
      has been used to both detect and stage a variety of malignancies. The current
      study examined the value of PET for preoperative staging of gastric
      adenocarcinoma. METHODS: Sixty-eight patients (49 males and 19 females) with
      gastric adenocarcinoma, who were referred for preoperative FDG-PET scans, were
      enrolled in this study. The patients underwent spiral-computed tomography (CT)
      within 1 week of referral. The final diagnosis in all patients was made by
      histologic and surgical findings. For quantitative PET analysis, the regional
      tumor FDG uptake was measured by the standardized uptake value (SUV). RESULTS:
      For the primary tumor of a gastric adenocarcinoma, PET demonstrated an increased
      uptake in 64 of 68 patients (sensitivity, 94%), with a mean SUV of 7.0 (range,
      0.9-27.7). A comparison of FDG uptake and clinicopathologic features showed
      significant association between FDG uptake and macroscopic type, tumor size,
      lymph node metastasis, histologic type, and TNM stage. The PET scan had a similar
      accuracy with that of CT for diagnosing local and distant lymph node metastases
      as well as peritoneal status. In assessing local lymph node status, however, PET
      had a higher specificity than CT (92% vs. 62%, P = 0.000). Moreover, PET had
      additional diagnostic value in 10 (15%) of 68 patients by upstaging 4 (6%) and
      downstaging 6 (9%) patients. PET combined with CT was more accurate for
      preoperative staging than either modality alone (66% vs. 51%, 66% vs. 47%,
      respectively; P = 0.002). CONCLUSIONS: FDG-PET improves the preoperative TNM
      staging of gastric adenocarcinoma. Based on its superior specificity, FDG-PET can
      facilitate the selection of patients for a curative resection by confirming a
      nodal status identified by CT.

PMID- 15856478
TI  - Salvage reoperation for complications after ileal pouch-anal anastomosis.
AB  - BACKGROUND: Surgical revision may be possible in patients with a poor outcome
      following ileal pouch-anal anastomosis (IPAA), using either a transanal approach
      or a combined abdominoperineal approach with pouch revision and reanastomosis.
      METHODS: Sixty-four patients underwent revisional surgery. The indication for
      salvage was sepsis in 47 patients, mechanical dysfunction in ten, isolated
      complications of the residual glandular epithelial cuff in three and previous
      intraoperative difficulties in four patients. RESULTS: A transanal approach was
      used in 19 patients and a combined abdominoperineal procedure in 45. Six of the
      latter had pouch enlargement and 25 received a new pouch. During a mean(s.d.)
      follow-up of 30(25) months, three patients required pouch excision because of
      Crohn's disease. Two patients had poor continence after abdominoperineal surgery.
      At last follow-up 60 (94 per cent) of 64 patients had a functional pouch. Half of
      the patients experienced some degree of daytime and night-time incontinence, but
      it was frequent in only 15 per cent. Of 58 patients analysed, 27 of 40 who had an
      abdominoperineal procedure and 13 of 18 who had transanal surgery rated their
      satisfaction with the outcome as good to excellent. CONCLUSION: Surgical revision
      after failure of IPAA was possible in most patients, yielding an acceptable level
      of bowel function in two-thirds of patients.

PMID- 15856479
TI  - Randomized clinical trial of daclizumab induction and delayed introduction of
      tacrolimus for recipients of non-heart-beating kidney transplants.
AB  - BACKGROUND: Kidneys from non-heart-beating donors (NHBDs) have high rates of
      delayed graft function (DGF). Use of calcineurin inhibitors is associated with a
      reduction in renal blood flow, which may delay graft recovery from ischaemic
      acute tubular necrosis. METHODS: To assess whether daclizumab (DZB) could safely
      replace tacrolimus in the immediate postoperative period, patients were
      randomized to receive DZB induction and daily mycophenolate mofetil with steroids
      (DZB group) or standard tacrolimus-based triple therapy (control group).
      Tacrolimus was given to patients in the DZB group when the serum creatinine level
      dropped below 350 micromol/l. RESULTS: Fifty-one patients were recruited at two
      centres over a 2-year interval between 2000 and 2003. The overall rate of
      immediate function was 28 per cent (13 of 46 grafts), with the highest rate in
      recipients of machine-perfused kidneys treated with DZB (eight of 15 patients).
      CONCLUSION: Induction with DZB and delayed introduction of tacrolimus reduced the
      incidence of DGF in recipients of machine-perfused NHBD kidneys.

PMID- 15856480
TI  - Comparison of X-ray and NMR structures: is there a systematic difference in
      residue contacts between X-ray- and NMR-resolved protein structures?
AB  - We have compared structures of 78 proteins determined by both NMR and X-ray
      methods. It is shown that X-ray and NMR structures of the same protein have more
      differences than various X-ray structures obtained for the protein, and even more
      than various NMR structures of the protein. X-ray and NMR structures of 18 of
      these 78 proteins have obvious large-scale structural differences that seem to
      reflect a difference of crystal and solution structures. The other 60 pairs of
      structures have only small-scale differences comparable with differences between
      various X-ray or various NMR structures of a protein; we have analyzed these
      structures more attentively. One of the main differences between NMR and X-ray
      structures concerns the number of contacts per residue: (1) NMR structures
      presented in PDB have more contacts than X-ray structures at distances below 3.0
      A and 4.5-6.5 A, and fewer contacts at distances of 3.0-4.5 A and 6.5-8.0 A; (2)
      this difference in the number of contacts is greater for internal residues than
      for external ones, and it is larger for beta-containing proteins than for all
      alpha proteins. Another significant difference is that the main-chain hydrogen
      bonds identified in X-ray and NMR structures often differ. Their correlation is
      69% only. However, analogous difference is found for refined and rerefined NMR
      structures, allowing us to suggest that the observed difference in interresidue
      contacts of X-ray and NMR structures of the same proteins is due mainly to a
      difference in mathematical treatment of experimental results.

PMID- 15856481
TI  - Structure alignment via Delaunay tetrahedralization.
AB  - A novel protein structure alignment technique has been developed reducing much of
      the secondary and tertiary structure to a sequential representation greatly
      accelerating many structural computations, including alignment. Constructed from
      incidence relations in the Delaunay tetrahedralization, alignments of the
      sequential representation describe structural similarities that cannot be
      expressed with rigid-body superposition and complement existing techniques
      minimizing root-mean-squared distance through superposition. Restricting to the
      largest substructure superimposable by a single rigid-body transformation
      determines an alignment suitable for root-mean-squared distance comparisons and
      visualization. Restricted alignments of a test set of histones and histone-like
      proteins determined superpositions nearly identical to those produced by the
      established structure alignment routines of DaliLite and ProSup. Alignment of
      three, increasingly complex proteins: ferredoxin, cytidine deaminase, and
      carbamoyl phosphate synthetase, to themselves, demonstrated previously identified
      regions of self-similarity. All-against-all similarity index comparisons
      performed on a test set of 45 class I and class II aminoacyl-tRNA synthetases
      closely reproduced the results of established distance matrix methods while
      requiring 1/16 the time. Principal component analysis of pairwise tetrahedral
      decomposition similarity of 2300 molecular dynamics snapshots of tryptophanyl
      tRNA synthetase revealed discrete microstates within the trajectory consistent
      with experimental results. The method produces results with sufficient efficiency
      for large-scale multiple structure alignment and is well suited to genomic and
      evolutionary investigations where no geometric model of similarity is known a
      priori.

PMID- 15856482
TI  - Comparison of experimental nerve injury caused by ultrasonically activated
      scalpel and electrosurgery.
AB  - BACKGROUND: Iatrogenic nerve injury caused by heat from dissection instruments is
      a significant problem in many areas of surgery. The aim of the present study was
      to compare the risk of nerve injury for three different dissection instruments:
      monopolar and bipolar electrosurgery (ES) and an ultrasonically activated (US)
      instrument. METHODS: The biceps femoris muscle was cut in a standard manner just
      adjacent to the sciatic nerve using monopolar ES, bipolar ES or US shears. A
      total of 73 functional experiments were conducted in which the nerve was
      isolated, divided proximally, and stimulated supramaximally in 37 anaesthetized
      rats. The electromyographic (EMG) potential was recorded distally before and
      after each experiment. Nerve dysfunction was defined as more than 10 per cent
      loss of the evoked EMG potential. Fifty-nine nerves were examined histologically
      after dissection with the different instruments. The extent of heat damage was
      determined in four nerves that were divided with ES bipolar scissors and five
      that were divided with US shears. RESULTS: Reduction in the EMG potential was
      significantly more frequent in the monopolar ES group than in the US group.
      Morphological examination also showed significantly less nerve damage in the US
      group. CONCLUSION: US instruments may be safer than ES for dissection close to
      nerves.

PMID- 15856483
TI  - Hydration of protein-protein interfaces.
AB  - We present an analysis of the water molecules immobilized at the protein-protein
      interfaces of 115 homodimeric proteins and 46 protein-protein complexes, and
      compare them with 173 large crystal packing interfaces representing nonspecific
      interactions. With an average of 15 waters per 1000 A2 of interface area, the
      crystal packing interfaces are more hydrated than the specific interfaces of
      homodimers and complexes, which have 10-11 waters per 1000 A2, reflecting the
      more hydrophilic composition of crystal packing interfaces. Very different
      patterns of hydration are observed: Water molecules may form a ring around
      interfaces that remain "dry," or they may permeate "wet" interfaces. A majority
      of the specific interfaces are dry and most of the crystal packing interfaces are
      wet, but counterexamples exist in both categories. Water molecules at interfaces
      form hydrogen bonds with protein groups, with a preference for the main-chain
      carbonyl and the charged side-chains of Glu, Asp, and Arg. These interactions are
      essentially the same in specific and nonspecific interfaces, and very similar to
      those observed elsewhere on the protein surface. Water-mediated polar
      interactions are as abundant at the interfaces as direct protein-protein hydrogen
      bonds, and they may contribute to the stability of the assembly.

PMID- 15856484
TI  - The molecular genetics and morphometry-based endometrial intraepithelial
      neoplasia classification system predicts disease progression in endometrial
      hyperplasia more accurately than the 1994 World Health Organization
      classification system.
AB  - BACKGROUND: The objective of this study was to compare the accuracy of disease
      progression prediction of the molecular genetics and morphometry-based
      Endometrial Intraepithelial Neoplasia (EIN) and World Health Organization 1994
      (WHO94) classification systems in patients with endometrial hyperplasias.
      METHODS: A multicenter, multivariate analysis was conducted on 477 patients with
      endometrial hyperplasia who were required to have a 1-year minimum disease-free
      interval from the time of the index biopsy (1-18 years of follow-up). The results
      from that analysis were compared with the results from 197 patients who had < 1
      year of follow-up. RESULTS: Twenty-four of 477 hyperplasias (5.0%) progressed to
      malignant disease over an average of 4 years (maximum, 10 years). According to
      the WHO94 classification, 16 of 123 atypical hyperplasias (13%) and 8 of 354
      nonatypical hyperplasias (2.3%) progressed (hazard ratio [HR] = 7). Twenty-two of
      118 EINs (19%) and 2 of 359 non-EINs (0.6%) progressed (HR = 45). EIN was
      prognostic within each WHO94 subcategory. Progression rates were 3% in simple
      hyperplasias, 22% in complex hyperplasias, 17% in simple atypical hyperplasias,
      and 38% in complex atypical hyperplasias with EIN, compared with progression
      rates of 0.0-2.0% in all hyperplasias if EIN was absent. EIN detected
      precancerous lesions (sensitivity, 92%) better than WHO94 atypical hyperplasias
      collectively (67%) or complex atypical hyperplasias alone (46%). In a Cox
      regression analysis, EIN was the strongest prognostic index of future endometrial
      carcinoma. The same was true for patients with < 1 year of follow-up (HR for EIN,
      atypical hyperplasia, and complex atypical hyperplasia: 58, 7, and 8,
      respectively). CONCLUSIONS: The EIN classification system predicted disease
      progression more accurately than the WHO94 classification and identified many
      women with benign changes that would have been regarded as high risk according to
      the WHO94 classification system.

PMID- 15856485
TI  - Detoxification enzymes in the duodenal mucosa of patients with familial
      adenomatous polyposis.

PMID- 15856486
TI  - Pathophysiology of anthracycline- and radiation-associated cardiomyopathies:
      implications for screening and prevention.
AB  - Great progress has been made in treating childhood cancers over the past 40
      years. Along with second malignancies, a major complication of anti-cancer
      therapies is adverse cardiovascular effects, especially cardiomyopathy and
      coronary artery disease. The pathophysiology and characteristics of
      cardiomyopathy associated with radiation therapy and anthracycline therapy are
      distinctive. We describe each type of cardiomyopathy, along with its risk
      factors. These distinctive cardiomyopathies require different screening tests.
      Appropriate screening of the entire cardiovascular system should be performed
      because radiation and chemotherapy affect the entire system. Prevention
      recommendations focus on cardiomyopathy and coronary artery disease.

PMID- 15856487
TI  - Comparison of column performances in direct high-performance liquid
      chromatographic enantioseparation of 1- or 3-methyl-substituted
      tetrahydroisoquinoline analogs. Application of direct and indirect methods.
AB  - The enantioseparability of 1- or 3-methyl-substituted tetrahydroisoquinolines was
      investigated by direct and indirect high-performance liquid chromatography. Alpha
      and beta-cyclodextrin-, macrocyclic glycopeptide- and cellulose-based chiral
      columns and isothiocyanate- and Sanger-type chiral derivatizing agents (CDAs)
      were applied to attain satisfactory enantioseparation. Of the chiral columns,
      beta-cyclodextrin-, vancomycin- and teicoplanin-containing macrocyclic
      glycopeptide-based columns appeared to be most suitable; of the CDAs, (1S,2R)-1
      acetoxy-1-phenyl-2-propyl isothiocyanate was most favorable. The differences
      between the selectivities of the columns and CDAs were compared and optimized to
      yield the best resolution.

PMID- 15856488
TI  - Determination of fluvoxamine in rat plasma by HPLC with pre-column derivatization
      and fluorescence detection using 4-fluoro-7-nitro-2,1,3-benzoxadiazole.
AB  - A sensitive, simple and reliable method using high-performance liquid
      chromatographic (HPLC) assay of fluvoxamine (FLU), a selective serotonin reuptake
      inhibitor (SSRI), in rat plasma after pre-column derivatization with 4-fluoro-7
      nitro-2,1,3-benzoxadiazole (NBD-F) was developed in this study. Extracted plasma
      samples were mixed with NBD-F at 60 degrees C for 5 min and injected into HPLC.
      Retention times of FLU and an internal standard (propafenone) derivative were
      15.5 and 13.5 min, respectively. The calibration curve was linear over the range
      0.015-1.5 microg/mL (r2 = 0.9985) and the lower limits of detection and
      quantification of FLU were 0.008 and 0.015 microg/mL, respectively, in 100 microL
      of plasma. The derivative sample was stable at 4 degrees C for 1 day. The
      coefficients of variation for intra-day and inter-day assay of FLU were less than
      8.3 and 9.6%, respectively. Other SSRIs and centrally acting drugs did not
      interfere with the peak of the FLU derivative. The method was applied for
      analysis of the plasma samples from rats treated with FLU. These results indicate
      that the method presented is useful to determine the FLU levels in rat plasma of
      volumes as small as 100 microL and can be applied to pharmacokinetic studies.

PMID- 15856489
TI  - Sensitive liquid chromatography-tandem mass spectrometry method for
      quantification of hydrochlorothiazide in human plasma.
AB  - A simple, rapid, sensitive and specific liquid chromatography-tandem mass
      spectrometry method was developed and validated for quantification of
      hydrochlorothiazide (I), a common diuretic and anti-hypertensive agent. The
      analyte and internal standard, tamsulosin (II) were extracted by liquid-liquid
      extraction with diethyl ether-dichloromethane (70:30, v/v) using a Glas-Col Multi
      Pulse Vortexer. The chromatographic separation was performed on a reversed-phase
      column (Waters symmetry C18) with a mobile phase of 10 mm ammonium acetate
      methanol (15:85, v/v). The protonated analyte was quantitated in negative
      ionization by multiple reaction monitoring with a mass spectrometer. The mass
      transitions m/z 296.1 solidus in circle 205.0 and m/z 407.2 solidus in circle
      184.9 were used to measure I and II, respectively. The assay exhibited a linear
      dynamic range of 0.5-200 ng/mL for hydrochlorothiazide in human plasma. The lower
      limit of quantitation was 500 pg/mL, with a relative standard deviation of less
      than 9%. Acceptable precision and accuracy were obtained for concentrations over
      the standard curve ranges. A run time of 2.5 min for each sample made it possible
      to analyze a throughput of more than 400 human plasma samples per day. The
      validated method has been successfully used to analyze human plasma samples for
      application in pharmacokinetic, bioavailability or bioequivalence studies.

PMID- 15856490
TI  - Application of polyacrylamide gel electrophoresis of fluorophore-labeled
      saccharides for analysis of hyaluronan and chondroitin sulfate in human and
      animal tissues and cell cultures.
AB  - Hyaluronan (HA) and chondroitin sulfate (CS) are glycosaminoglycans (GAGs) with
      great importance in biological events, since they participate in and regulate
      cell adhesion, migration and proliferation. Quantitation and analysis of the fine
      structure of GAGs are increasingly important for understanding many biological
      processes, among which are many critical aspects of pathology development and
      specific phenotype descriptions. Human umbilical cord and human synovial fluid
      are connective tissues containing high amounts of GAGs and change in the quantity
      and structure of these macromolecules is described in tissue development and is
      commonly associated with disease. Moreover, also in Xenopus laevis embryo
      development and chondrocyte cultures, the GAG content and structure play a
      critical role. A rapid analysis of hyaluronan and chondroitin sulfate Delta
      disaccharides derived from the above human and animal samples, derivatized with 2
      aminoacridone and analyzed by polyacrylamide gel electrophoresis, is described in
      this report. Qualitative and quantitative analysis were performed by comparing
      their migration and the pixel density with standard Delta-disaccharides, running
      in the same gel. Since this method allows the analysis of large numbers of
      samples simultaneously in one gel and has a relatively high sensitivity (less
      than 25 pmol), it is suggested as a cost-effective and useful tool for the fast
      screening of small amounts of hyaluronan and chondroitin sulfate disaccharides.

PMID- 15856491
TI  - Endoscopic treatment of large primary adrenal tumours.
AB  - BACKGROUND: Endoscopic adrenalectomy has become the treatment of choice for small
      benign adrenal tumours but should not be used for malignant lesions. It is
      debatable whether large and therefore potentially malignant primary adrenal
      tumours should be removed by minimally invasive techniques. METHODS: Three
      hundred and eighty primary adrenal tumours in 368 patients (142 male and 226
      female; mean(s.d.) age 48.9(14.4) years) were excised by laparoscopic or
      retroperitoneoscopic adrenalectomy. Adrenal neoplasias exceeded 6 cm in diameter
      (range 6-13 cm) in 33 patients (18 male and 15 female; age 42.6(14.2) years).
      RESULTS: There were no deaths. Patients with large tumours had an increased
      conversion rate (P = 0.039), longer operating time (P < 0.001) and greater
      intraoperative blood loss (P = 0.007) than those with smaller lesions, but a
      similar overall morbidity rate (P = 0.207). Six malignant tumours were identified
      (diameter 4-10 cm; four phaeochromocytomas and two adrenocortical carcinomas).
      Local recurrence developed in two patients and distant metastasis occurred in all
      six patients with malignant lesions. CONCLUSION: Endocopic adrenalectomy perfomed
      by an experienced surgeon should be the treatment of choice for tumours exceeding
      6 cm in diameter.

PMID- 15856492
TI  - Identification and quantification of the plasma volume expander dextran in human
      urine by liquid chromatography-tandem mass spectrometry of enzymatically derived
      isomaltose.
AB  - Plasma volume expanders are used in sports in order to control haematological
      parameters and/or to mask erythropoietin (EPO) misuse. A reliable method based on
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for
      doping control purposes, enabling the identification and quantification of the
      plasma volume expander dextran in human urine. The dextran polymer was
      enzymatically hydrolysed by alpha-1,6-glucosidase (dextranase) followed by
      acetylation of the generated isomaltose subunits, allowing the chromatographic
      separation of different disaccharides, such as lactose, saccharose and
      isomaltose, as well as the identification and quantification of the analyte in
      human urine. The method was used to determine the basal concentration of
      isomaltose resulting from the enzymatic hydrolysis of polymeric 1,6-linked
      glucose in 238 routine doping control samples. In addition the concentration of
      dextran measured as isomaltose was estimated in seven urine specimens obtained
      from patients treated with dextran. Calibration curves for dextran were linear
      and reproducible. The inter- and intra-assay coefficients of variation for
      dextran ranged from 4.9 to 7.3% at three concentration levels between 53 and 1186
      microg/mL. Recovery ranged from 97 to 112% (mean 106.9%). The assay limit of
      detection was 3.8 microg/mL and the lower limit of quantification was 12.5
      microg/mL. In 96% of the investigated doping control samples, the concentrations
      of isomaltose were below the LLOQ of 12.5 microg/mL. Even the highest
      concentrations were approximately 100-300-fold lower than concentrations found in
      urine samples of patients after intravenous application of dextran. The presented
      results demonstrate the capability and reliability of the developed LC-MS/MS
      method for the identification and quantification of dextran in human urine and
      can be regarded as a method revealing the misuse of dextran in sports.

PMID- 15856493
TI  - Childhood obesity and attention deficit/hyperactivity disorder: a newly described
      comorbidity in obese hospitalized children.
AB  - OBJECTIVE: The current study described a subgroup of children presenting with
      obesity and comorbid attention deficit/hyperactivity disorder (AD/HD) and
      assessed a possible casual relationship. METHOD: School-aged children
      hospitalized for obesity (body mass index [BMI] >85%) in a tertiary referral
      center underwent extensive evaluations and were prospectively assessed for
      comorbid AD/HD. RESULTS: During a 4-year period, 32 obese school-aged children
      were hospitalized and 26 were included in the current study. We found that over
      one half (57.7%) suffered from comorbid AD/HD. DISCUSSION: AD/HD shows a high
      comorbidity among obese hospitalized children. The characteristic difficulty in
      regulation found in AD/HD may be a risk factor for the development of abnormal
      eating behaviors leading to obesity. We suggest that obese children should be
      screened routinely for AD/HD.

PMID- 15856494
TI  - Effect of orthotopic small bowel transplantation on mineral metabolism in an
      experimental model.
AB  - BACKGROUND: Numerous experimental models have been described for investigation of
      short bowel syndrome. The aim of this study was to examine the effect of
      orthotopic small bowel transplantation (OSBT) on universal metabolism in an
      inbred rat model, with particular emphasis on mineral metabolism. METHODS:
      Jejunoileal resection and syngeneic OSBT was performed in 12-week-old male Lewis
      rats. Metabolic studies were performed over the following 16 weeks. Bones were
      analysed by physicochemical methods, dual X-ray absorptiometry, biomechanical
      procedures and histomorphometry. Biochemical markers of bone turnover were also
      measured. RESULTS: Jejunoileal resection induced severe short bowel syndrome with
      profoundly reduced food efficiency, bone size, fracturing energy and bone mineral
      content, but no cancellous bone osteopenia. After OSBT rats showed normal growth;
      bones were of normal size, and bone mineral content and fracturing energy were
      similar to those in sham-operated controls. However, tibial, but not vertebral,
      cancellous bone osteopenia was found after transplantation. CONCLUSION: OSBT with
      portal venous drainage achieves almost optimal mineral and bone metabolism. In
      the absence of immunosuppressive therapy, OSBT does not appear to have major
      untoward side-effects on bone in rats.

PMID- 15856495
TI  - The relationship between friendship factors and adolescent girls' body image
      concern, body dissatisfaction, and restrained eating.
AB  - OBJECTIVE: This study examined whether poorer friendship relations predict weight
      concerns and dietary restraint in adolescent girls. METHOD: Questionnaires were
      administered to 131 Year 9 and Year 10 girls to assess the relationship between
      acceptance by friends, perceived social support, friendship intimacy, and
      perceived impact of thinness on male (PITOF-M) and female (PITOF-F) friendships
      on the one hand, and body image concern, body dissatisfaction, and restrained
      eating on the other. RESULTS: Friendship variables contributed significantly to
      the prediction of body image concern, body dissatisfaction, and restrained
      eating. The largest unique contribution to prediction was from the PITOF-M. Poor
      acceptance by friends significantly predicted the PITOF-M and PITOF-F. Whereas
      heavier girls were more likely to believe being thinner would improve their
      friendships, they did not experience poorer friendships. DISCUSSION: Results
      suggest sociocultural risk factors for disordered eating and underline the
      importance of perceived peer affiliation on girls' body image concern and
      dieting.

PMID- 15856496
TI  - Body checking and avoidance in overweight patients with binge eating disorder.
AB  - OBJECTIVE: Repetitive body checking and avoidance are viewed as behavioral
      manifestations of the core psychopathology of eating disorders (EDs). We examined
      select body checking and avoidance behaviors in overweight patients with binge
      eating disorder (BED). METHOD: Three hundred seventy-seven overweight (body mass
      index [BMI] > or = 25) treatment-seeking BED patients (80 men and 297 women) were
      administered measures to assess body checking and avoidance, other key behavioral
      features of EDs (binge eating, dietary restraint, and disinhibition), and the
      core psychopathology of EDs (overevaluation of weight and shape). RESULTS: The
      majority of participants reported regularly pinching areas of their body to check
      for fatness and avoided wearing clothing that made them particularly aware of
      their body. Significant associations emerged between checking and restraint, and
      conversely, between avoidance and binge eating. Both checking and avoidance were
      positively and significantly associated with overevaluation of weight and shape,
      even after controlling for their unique effects. DISCUSSION: These findings offer
      support to the potential role of checking and avoidance behaviors in the
      maintenance of BED.

PMID- 15856497
TI  - An unusual cause of dizziness in bulimia nervosa: a case report.
AB  - OBJECTIVE: The current article describes the case of a 23-year-old female with
      purging-type bulimia nervosa who was evaluated by her primary care physician for
      dizziness and lightheadedness. METHODS: After laboratory studies were performed
      by her primary care physician, the patient was admitted to the hospital because
      of severe anemia. The patient had been taking nonsteroidal antiinflammatory drugs
      (NSAIDS) at prescribed doses for shin splints that were secondary to jogging and
      developed gastric erosion. RESULTS: Endoscopic examination showed that she had
      diffuse gastritis with linear, streaky ulcerations throughout the body of the
      stomach. DISCUSSION: Lightheadedness is a common clinical symptom among
      individuals with eating disorders, but is typically related to dehydration,
      malnutrition, hypometabolism, and/or combinations of these factors. Clinicians
      need to consider NSAID use, which may cause erosive gastritis, blood loss, and
      lightheadedness.

PMID- 15856498
TI  - Treatment of overweight in children and adolescents: does dieting increase the
      risk of eating disorders?
AB  - OBJECTIVE: Overweight is a serious health problem in children and adolescents.
      Some investigators fear that dieting, the principal method of reducing body
      weight, may precipitate eating disorders and related complications. This review
      examined the literature on the effects of dieting on eating behavior and
      psychological status in youth. METHOD: Electronic databases were searched for
      articles containing combinations of the following keywords: weight loss, dieting,
      treatment, overweight, obesity, anorexia, bulimia, binge eating, eating disorder,
      children, and adolescents. A manual search of reference lists also was conducted.
      RESULTS: Five relevant studies were found. Their findings suggest that a
      professionally administered weight loss poses minimal risks of precipitating
      eating disorders in overweight children and adolescents. Significant improvements
      in psychological status also were observed in several studies. DISCUSSION:
      Concerns about potential ill effects of dieting should not dissuade overweight
      youth from pursuing sensible methods of weight loss.

PMID- 15856499
TI  - Binge eating and self-esteem predict body image dissatisfaction among obese men
      and women seeking bariatric surgery.
AB  - OBJECTIVE: We examined body image dissatisfaction (BID) in extremely obese men
      and women seeking bariatric surgery. METHODS: The following predictors of BID
      were examined in a consecutive series of 260 (44 men and 216 women) gastric
      bypass candidates: gender, ethnicity, body mass index (BMI), age at onset of
      overweight, childhood maltreatment, binge eating, depression, and self-esteem.
      RESULTS: Women reported significantly higher levels of BID than men. Stepwise
      multiple regression analyses revealed that gender, binge eating, and self-esteem
      levels accounted for 41% of the variance in BID. In predicting BID levels
      separately by gender, binge eating and self-esteem accounted for 56% of the
      variance among men and for 33% of the variance among women. DISCUSSION: Among
      bariatric surgery candidates, women reported significantly higher BID than men.
      Our findings suggest the importance of binge eating and lower self-esteem for
      understanding BID in both men and women who are extremely obese.

PMID- 15856500
TI  - Fear of negative evaluation and eating attitudes: a replication and extension
      study.
AB  - OBJECTIVE: Preliminary research has found a link between restrictive eating
      attitudes and a fear of negative evaluation (FNE). However, such work has focused
      exclusively on these fears in relation to people in general. The current study
      sought to replicate and extend these findings by exploring links between
      restriction and FNE in relation to close friends and relatives. METHOD: Ninety
      one young women completed two versions of the short Fear of Negative Evaluation
      Scale (FNE). First, they completed the standard scale (in relation to people in
      general), and then an amended version (in relation to close friends and
      relatives). Next, they completed the three eating-related subscales of the Eating
      Disorders Inventory (EDI). RESULTS: For the whole group, both general and close
      FNE were significantly and positively correlated with restrictive (drive for
      thinness and body dissatisfaction), but not with bulimic attitudes. However, only
      general FNE had significant individual predictive power on restrictive attitudes
      when these two forms of FNE were entered into a regression analysis. DISCUSSION:
      Among nonclinical populations, negative evaluation fears regarding people in
      general are linked with restrictive but not with bulimic psychopathology.

PMID- 15856501
TI  - Emotion-processing deficits in eating disorders.
AB  - OBJECTIVE: First, we measured both emotional awareness and alexithymia to
      understand better emotion-processing deficits in eating disorder patients (EDs).
      Second, we increased the reliability of the measures by limiting the influence of
      confounding factors (negative affects). METHOD: Seventy females with eating
      disorders were compared with 70 female controls. Participants completed the Beck
      Depression Inventory (BDI; depression), the Hospital and Anxiety Depression Scale
      (HADS; anxiety), the Toronto Alexithymia Scale (TAS; alexithymia), and the Level
      of Emotional Awareness Scale (LEAS). RESULTS: EDs exhibited higher alexithymia
      scores and lower LEAS scores, with an inability to identify and describe their
      own emotions, as well as an impairment in mentalizing others' emotional
      experience. Whereas alexithymia scores were related to depression scores, LEAS
      scores were not. After controlling for depression, alexithymia scores were
      similar in EDs and controls. DISCUSSION: The marked impairment in emotion
      processing found in EDs is independent of affective disorders. Thus, the joint
      use of TAS and LEAS suggests a global emotion-processing deficit in EDs.

PMID- 15856502
TI  - Factor structure of the Eating Disorder Inventory-C.
AB  - OBJECTIVE: The Eating Disorder Inventory-C (EDI-C) is a multidimensional self
      report questionnaire for children and adolescents used to characterize
      differences in the symptoms of eating disorders. It is based on the EDI-2
      questionnaire, which is designed for adults. Although the psychometric properties
      of the EDI and EDI-2 have been well characterized, no studies exist on the EDI-C.
      Thus, we aimed to establish the factor structure of the EDI-C questionnaire among
      children. METHOD: A nonclinical sample of 898 children aged 9-16 years completed
      the EDI-C questionnaire at school. RESULTS: Instead of the original 11-factor
      structure of the EDI-2, 5 factors with high reliability were extracted when 27
      items with low communality were removed from analysis. DISCUSSION: When the EDI-C
      is used, the reliability of the original 11 factors may be low. A modified
      subscale structure with five factors is proposed.

PMID- 15856503
TI  - Impact of traumatic experiences and violent acts upon response to treatment of a
      sample of Colombian women with eating disorders.
AB  - OBJECTIVE: The current article compared the impact of exposure to sexual trauma
      and other types of physical threats against the patient or the patient's family
      on response to treatment, relapse, and dropout rates in 160 Colombian women
      between 12 and 49 years of age with eating disorders. METHOD: A comparison was
      made to 70 cases with unsatisfactory response to treatment and 90 controls with a
      better response to treatment goals. RESULTS: Forty-five percent had a history of
      sexual abuse, other violent traumas, or both. Significant statistical differences
      were observed between both groups in exposure variables. The highest probability
      of poor outcome was observed in patients with sexual abuse and exposure to other
      violent acts (odds ratio [OR] = 6.37, 95% confidence interval [CI] = 2.1-19.07).
      The risk of dropout or relapse was, respectively, 10 and 3 times greater among
      those exposed. DISCUSSION: Violent social conditions should be noted as another
      form of trauma with potential impact on outcome in Colombian women with eating
      disorders. (

PMID- 15856504
TI  - Fear of negative evaluation and the development of eating psychopathology: a
      longitudinal study among nonclinical women.
AB  - OBJECTIVE: We replicated the cross-sectional relationship between restrictive
      eating attitudes and a fear of being negatively evaluated by others and tested
      whether negative evaluation fears longitudinally predict changes in eating
      attitudes over a 7-month period. METHOD: During the first week of an academic
      year, and again during Week 33, 143 female students completed the Fear of
      Negative Evaluation Scale (FNE), the Rosenberg Self-Esteem Scale (RSE), the
      Hospital Anxiety and Depression Scale (HADS), and the three eating scales of the
      Eating Disorders Inventory (EDI). RESULTS: The exclusive link between heightened
      negative evaluation fears and restrictive eating attitudes was replicated cross
      sectionally. However, the longitudinal model predicting the development of
      restriction was nonsignificant. In contrast, alongside depression, negative
      evaluation fears predicted an increase in bulimic attitudes, whereas self-esteem
      predicted an increase in body dissatisfaction. DISCUSSION: The findings support a
      model whereby individuals with heightened fears of negative evaluation may use
      restrictive pathology to raise their status among peers. If this mechanism of
      dealing with negative evaluation fears is not sufficient in the long term,
      individuals may develop bulimic symptoms to deal with their negative evaluation
      fears.

PMID- 15856505
TI  - Treatment preferences of patients with binge eating disorder.
AB  - OBJECTIVE: The current study examined the treatment preferences of obese patients
      with binge eating disorder (BED). METHOD: Participants were 103 consecutive
      patients with BED who responded to advertisements for treatment studies looking
      for persons who wanted to "stop binge eating and lose weight." In addition to
      completing comprehensive assessment batteries, participants were provided
      descriptions of cognitive-behavioral therapy (CBT) and behavioral weight loss
      therapy (BWL) after which they were asked to choose and rate their preferred
      treatment. RESULTS: Sixty-three percent of participants stated they preferred
      CBT. Treatment preferences were not associated with (1) histories of obesity,
      dieting, binge eating, or weight cycling, (2) current obesity or eating disorder
      features, or (3) psychological features such as depression or self-esteem levels.
      In contrast, participants' stated treatment preferences were aligned with their
      perception of their primary problem (eating disorder vs. obesity) and their
      primary goals for treatment (stop binge eating vs. lose weight). The patients who
      preferred CBT based their treatment selection more on their problem perception
      than on their primary treatment goal, whereas the patients who preferred BWL
      selected treatment based more on their primary treatment goal (weight loss) than
      on their problem perception. DISCUSSION: Obese patients with BED express
      treatment preferences that are not associated with variability in their clinical
      characteristics but are aligned with their perception of their primary problem
      and with their primary goals for treatment.

PMID- 15856506
TI  - Fertility and history of sexual abuse at 10-year follow-up of adolescent-onset
      anorexia nervosa.
AB  - OBJECTIVE: We studied fertility and history of child sexual abuse (CSA) in a
      representative group of anorexia nervosa (AN) cases. METHOD: Fifty-one adolescent
      onset AN cases recruited after community screening and 51 matched comparison
      cases were interviewed 10 years after reported AN onset, at mean age 24 years,
      regarding children, miscarriages, and fertility problems. They completed
      anonymously the Finkelhor self-report questionnaire regarding history of CSA.
      RESULTS: There were few fertility problems in our AN population. There was a
      tendency towards more subjects in the AN group to give birth to a child (10 AN
      and 4 comparison mothers). The prevalence of CSA was equal between groups. For
      example, 6% in each group had experienced CSA before the age of 10 years, and 14%
      of the AN and 12% of the comparison cases reported CSA. DISCUSSION: Infertility
      and history of CSA may not be overrepresented in a population-based AN sample at
      long-term follow-up.

PMID- 15856507
TI  - Autofluorescence and diffuse reflectance spectroscopy for oral oncology.
AB  - BACKGROUND AND OBJECTIVES: Autofluorescence and diffuse reflectance spectroscopy
      have been used separately and combined for tissue diagnostics. Previously, we
      assessed the value of autofluorescence spectroscopy for the classification of
      oral (pre-)malignancies. In the present study, we want to determine the
      contributions of diffuse reflectance and autofluorescence spectroscopy to
      diagnostic performance. STUDY DESIGN/MATERIALS AND METHODS: Autofluorescence and
      diffuse reflectance spectra were recorded from 172 oral lesions and 70 healthy
      volunteers. Autofluorescence spectra were corrected in first order for blood
      absorption effects using diffuse reflectance spectra. Principal Components
      Analysis (PCA) with various classifiers was applied to distinguish (1) cancer and
      (2) all lesions from healthy oral mucosa, and (3) dysplastic and malignant
      lesions from benign lesions. Autofluorescence and diffuse reflectance spectra
      were evaluated separately and combined. RESULTS: The classification of cancer
      versus healthy mucosa gave excellent results for diffuse reflectance as well as
      corrected autofluorescence (Receiver Operator Characteristic (ROC) areas up to
      0.98). For both autofluorescence and diffuse reflectance spectra, the
      classification of lesions versus healthy mucosa was successful (ROC areas up to
      0.90). However, the classification of benign and (pre-)malignant lesions was not
      successful for raw or corrected autofluorescence spectra (ROC areas <0.70). For
      diffuse reflectance spectra, the results were slightly better (ROC areas up to
      0.77). CONCLUSIONS: The results for plain and corrected autofluorescence as well
      as diffuse reflectance spectra were similar. The relevant information for
      distinguishing lesions from healthy oral mucosa is probably sufficiently
      contained in blood absorption and scattering information, as well as in corrected
      autofluorescence. However, neither type of information is capable of
      distinguishing benign from dysplastic and malignant lesions. Combining
      autofluorescence and reflectance only slightly improved the results.

PMID- 15856508
TI  - Reorganization of cytoskeleton induced by 5-aminolevulinic acid-mediated
      photodynamic therapy and its correlation with mitochondrial dysfunction.
AB  - BACKGROUND AND OBJECTIVES: This study investigated the early cellular events
      which occurred after mitochondrial photodamage induced by 5-aminolevulinic acid
      mediated photodynamic therapy (ALA-PDT). STUDY DESIGN/MATERIALS AND METHODS:
      Subcellular localization of protoporphyrin IX (PpIX) in NIH3T3 cells was studied
      by confocal microscopy. Mitochondrial damage was assessed by measuring
      mitochondrial transmembrane potential and ATP contents, and confirmed by
      characteristic appearance on transmission electron microscopy. Cellular adhesion
      was measured by the level of resistance to trypsinization. Cytoskeletal studies
      were performed by fluorescent staining of cytoskeletal components. RESULTS:
      Following ALA-PDT, mitochondrial damage was found in NIH3T3 cells as judged by
      the decrease of membrane potential and ATP contents. Mitochondrial photodamage
      was further confirmed by electron microscopy. Resistance to trypsinization after
      ALA-PDT was shown to be light dose-dependent. The increase of cellular adhesion
      after ALA-PDT was correlated with mitochondrial photodamage and reorganization of
      cytoskeletal components in NIH3T3 cells. CONCLUSIONS: This study has demonstrated
      that mitochondrial dysfunctions induced by ALA-PDT results in alterations of
      cellular morphology and cellular adhesion.

PMID- 15856509
TI  - Studies of a vascular-acting photosensitizer, Pd-bacteriopheophorbide (Tookad),
      in normal canine prostate and spontaneous canine prostate cancer.
AB  - BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) mediated with Tookad (Pd
      bacteriopheophorbide, WST09) was investigated pre-clinically as part of a program
      to develop an alternative modality for treating prostate cancer. STUDY
      DESIGN/MATERIALS AND METHODS: Spontaneous canine prostate cancer and normal
      canine prostate were used as the animal models. Interstitial PDT was performed by
      IV infusion of the photosensitizer and irradiating the prostates with a diode
      laser (763 nm). The prostates were harvested 1-week post-PDT and subjected to
      histopathologic examinations. The effects of the drug doses and light doses were
      studied for one- and two-session PDT. Pharmacokinetics were studied using HPLC
      assay. The feasibility of using perfusing CT scans for assessing PDT lesions was
      also evaluated. RESULTS: Tookad is a vascular-acting drug and clears rapidly from
      the circulation. Tookad-PDT-induced lesions, in both normal and cancerous
      prostates, were characterized by marked hemorrhagic necrosis. CONCLUSIONS: Tookad
      PDT is very effective in ablating prostatic tissue through its vascular effects.

PMID- 15856510
TI  - In vitro study of the variable square pulse Er:YAG laser cutting efficacy for
      apicectomy.
AB  - BACKGROUND AND OBJECTIVES: Variable square pulse (VSP) Er:YAG laser should be
      quicker than older Er:YAG lasers. The objectives were: (1) comparison of VSP
      laser and mechanical handpiece efficacy for apicectomy and (2) determination of
      optimal pulse width/energy/frequency combination. STUDY DESIGN/MATERIALS AND
      METHODS: Sixty extracted, single-rooted mature human teeth with round apical
      parts were instrumented, root filled, cleaned, and divided into four groups.
      Apical 2 mm of each root were apicectomized with mechanical handpiece and Er:YAG
      laser with three different settings (LaserA = 200 mJ/300 microseconds/ 8 Hz;
      LaserB = 200 mJ/100 microseconds/8 Hz; LaserC = 380 mJ/100 microseconds/20 Hz).
      Timing results were statistically compared. RESULTS: LaserC was the most
      efficient setting. Differences between groups were significant except between
      LaserC-Mechanical and LaserA-LaserC (P < 0.05). CONCLUSIONS: VSP Er:YAG laser
      used for apicectomy is slower by a factor of 7-31 than mechanical handpiece, but
      treatment outcome is acceptable. Optimal settings for apicectomy with VSP laser
      are 380 mJ/100 microseconds/20 Hz.

PMID- 15856511
TI  - Evaluation of postmyomectomy uterine scar.
AB  - PURPOSE: To determine preoperative and intraoperative factors that affect the
      healing pattern of a myomectomy uterine incision and to estimate the incidence
      and outcome of postmyomectomy hematoma demonstrated with sonography. METHODS:
      This observational longitudinal prospective study followed the course of patients
      diagnosed with at least 1 leiomyomata. Each patent was scheduled for abdominal
      myomectomy. Preoperative assessments included sonographic measurement of the
      uterine volume as well as identification of the numbers and sites of the
      leiomyomata. Detailed operative notes were reported for every patient.
      Transvaginal sonography was performed for all cases on day 2, day 7, and at 1
      month and 3 months postoperatively. The main outcome measure was the occurrence
      of postoperative hematoma versus preoperative and postoperative factors that
      possibly affect uterine healing. RESULTS: We found a statistically significant
      reduction of the uterine volume on follow-up (P < 0.001) of the 169 women
      enrolled. Hematoma in the myomectomy bed was observed postoperatively in 40 (24%)
      28 (17%) and 12 (7%) patients on day 2, day 7, and 1 month, respectively. A
      preoperative myoma size greater than 110 cm(3), the use of a tourniquet, and the
      experience of the surgeon were significantly correlated with formation of uterine
      scar hematomas. CONCLUSIONS: The postoperative sonographic diagnosis of wound
      hematoma may be used as an indicator of wound healing that is usually complete
      within 3 months. Use of a tourniquet is frequently associated with hematoma
      formation. Myomectomy should usually be performed by an experienced surgeon
      without a tourniquet, using microsurgical principles, especially when the sizes
      of the leiomyomata exceed 110 cm(3).

PMID- 15856512
TI  - Cardiac hydatid cysts: echocardiographic findings.
AB  - Cardiac hydatid disease is rare. Many patients are asymptomatic, hence cardiac
      involvement is often discovered incidentally. Diagnosis is also difficult because
      of a long period between parasitic infection and the manifestation of disease.
      Rupture of a cardiac cyst is a serious complication. Diagnosis of cardiac hydatid
      cysts is often made using transthoracic echocardiography (TTE) and
      transesophageal echocardiography (TEE) provides details of the cysts. We present
      the cases of 3 patients with nonspecific symptoms of their endemic parasitic
      disease. The results of sonographic examinations in all patients strongly
      suggested the presence of cardiac hydatid cysts. One patient had a cyst in the
      external surface of the left ventricular apical-lateral wall visualized with TTE
      and TEE. Parasitic serology was negative. She underwent surgery, which confirmed
      a cyst located in the pericardium, and then was treated with albendazole. Another
      patient had a cyst in the left ventricle demonstrated by TTE and TEE and
      confirmed with serology. Color Doppler sonography verified that her cardiac cyst
      was in communication with the left ventricle. She was not a surgical candidate
      and was treated with albendazole. The final patient had a septated cyst in the
      media basilar portion of the interventricular septum demonstrated using TTE, and
      CT. He refused surgical treatment and albendazole was prescribed. Chest
      radiographs in 3 patients failed to show the cysts, and serology in 1 patient
      failed to indicate a hydatid cyst. Follow-up at 1-2 years revealed no recurrence
      in any patient. In all 3 cases, cysts could be visualized from the subcostal view
      via echocardiography. Imaging is critical for the early diagnosis, assessment,
      and follow-up of patients with this disease.

PMID- 15856513
TI  - Effects of sildenafil on major arterial blood flow using duplex sonography.
AB  - PURPOSE: Erectile dysfunction (ED) is the persistent inability to achieve or
      maintain an erection sufficient for satisfactory sexual performance. Oral use of
      sildenafil citrate is effective in the treatment of ED. Although the effects of
      sildenafil citrate have been investigated in several systems, its effect on
      aortic, superior mesenteric (SMA), and carotid artery blood flow is still
      unclear. The aim of this study is to investigate the early phase effects of
      sildenafil citrate on aortic, SMA, and carotid artery blood flow using color
      duplex sonography (CDS). METHODS: Thirty-four patients with ED (aged 19-71) were
      included in this study. Peak systolic velocity, end diastolic velocity, and
      resistance index (RI) in aorta, SMA, and bilateral common and internal carotid
      arteries were measured at baseline and 45-75 minutes after the administration of
      sildenafil citrate using CDS. RESULTS: Statistically significant changes were
      observed in only 3 of 18 parameters: an increase in post drug values of bilateral
      internal carotid artery peak systolic velocity (Vmax) compared to baseline values
      and a significant decrease in the RI value of the left main carotid artery after
      drug administration compared to baseline values. CONCLUSIONS: Sildenafil citrate
      had no significant effect on aortic and SMA circulation and only caused mild
      changes in the carotid artery circulation. Although these alterations may be
      considered clinically insignificant, further studies assessing long-term effects
      of sildenafil are warranted.

PMID- 15856514
TI  - Measuring resistance index in patients with BPH and lower urinary tract symptoms.
AB  - PURPOSE: To assess the correlation between resistance index (RI) measured in
      different zones of the prostate and other more commonly used parameters of benign
      prostatic hyperplasia (BPH). METHODS: Twenty-six male patients who underwent a
      detailed evaluation for lower urinary tract symptoms suggestive of BPH were
      examined with transrectal (TRUS) color Doppler sonography (CDS). The correlation
      between RI in various prostate zones, and various urinary flow rates, and the
      International Prostate Symptom Score (IPSS), and prostatic volume measured by
      TRUS was determined. RESULTS: No significant difference in RI was observed
      between right and left transition (TZ) and peripheral zones (PZ) in the prostate
      (P > 0.05). There was a significant correlation between mean RI and maximum
      urinary flow rate (Qmax) and mean RI in both zones (r = -0.48 for TZ and r = 
      0.39, P < 0.05 for PZ). Individual measurements in left and right TZ RI were also
      correlated with Qmax. There was a correlation between prostatic volume and both
      the right (P < 0.05, r = 0.56) and the left (P < 0.05, r = 0.58) TZ RI,
      respectively. CONCLUSION: Our results demonstrate the potential value of RI
      measurement in the evaluation of patients with lower urinary tract symptoms
      suggestive of BPH.

PMID- 15856515
TI  - Prenatal diagnosis of transposition-like double-outlet right ventricle with
      mitral valve atresia in heterotaxy syndrome.
AB  - We present a case of heterotaxy syndrome with right isomerism detected in a twin
      fetus, with the sonographic findings that established this diagnosis. At 24
      weeks' menstrual age, ultrasound detected anomalies in the heart suggestive of
      heterotaxy syndrome. Intrauterine fetal echocardiography demonstrated that the
      heart of the affected twin was located on the left side with a normal cardiac
      axis. The right ventricle was much larger than the left ventricle. The appearance
      of the mitral valve was dysplastic with restricted motion. The ascending aorta
      exited from the right ventricle, anterior to, right to, and parallel to the
      smaller pulmonary trunk, which also arose from the right ventricle. Double-outlet
      right ventricle (DORV) was clearly demonstrated. Cesarean section was performed
      at 38 weeks' menstrual age. Both twins were healthy and survived. Postnatal
      echocardiography and MRI confirmed the prenatal findings. At the age of 4 months,
      the affected infant had no evidence of cardiac decompensation. This report shows
      that conventional ultrasound can be used to detect heterotaxy syndrome and that
      intrauterine fetal echocardiography can delineate the cardiac complex in
      heterotaxy syndrome. Postnatal surgery with complex Fontan procedures was planned
      for the affected twin.

PMID- 15856516
TI  - Hypoechoic focal liver lesions: characterization with contrast enhanced
      ultrasonography.
AB  - PURPOSE: To evaluate the late sinusoidal phase of contrast enhancement with a 2nd
      generation ultrasound contrast enhanced medium in the characterization of
      hypoechoic focal liver lesions. METHODS: We studied 88 hypoechoic liver lesions
      (diameter range, 1-18 cm; with 18 lesions 2 cm or less) found on conventional
      grayscale sonography (US) with contrast-enhanced ultrasonography (CEUS). Final
      diagnosis was made using contrast enhanced helical CT, contrast enhanced MR,
      angiography (DSA), and/or histopathic confirmation or clinical imaging follow-up.
      RESULTS: There were 37/88 benign lesions demonstrated: 17 cavernous hemangiomas,
      3 capillary hemangiomas, 11 focal nodular hyperplasias (FNH), 3 focal areas of
      sparing in hepatic steatosis, 2 adenomas, and 1 intrahepatic necrotic area.
      Malignant lesions demonstrated included 51/88: 27 hepatocellular carcinomas (HCC)
      in cirrhosis, 11 metastatic carcinomas, 10 metastatic endocrine tumors, 2
      cholangiocellular carcinomas (CCC) and 1 non-Hodgkin's lymphoma (NHL). CEUS
      characterized 30/37 (81%) benign lesions and 45/51 (88%) malignant lesions. On
      the basis of the results obtained during the sinusoidal contrast enhanced phase
      of CEUS, diagnosis of benignancy was possible in 35/37 (95%) of benign liver
      lesions and diagnosis of malignancy in 49/51 (96%) of malignant liver lesions.
      The enhancement pattern of 13 small (< or = 2 cm in diameter) hypervascular liver
      lesions (3 capillary hemangiomas, 2 FNHs, 4 HCCs, 4 metastatic endocrine tumors)
      was better demonstrated on CEUS than on helical CT. In these cases the hyper
      vascularization of the lesions shown on CEUS was not confirmed on CT.
      CONCLUSIONS: CEUS distinguished malignant from benign hypoechoic liver lesions
      with an accuracy of 95%.

PMID- 15856517
TI  - Diagnosis of early intramural ectopic pregnancy.
AB  - Intramural ectopic pregnancy is a very rare diagnosis. Establishing a diagnosis
      is difficult and is often made intraoperatively. Demonstration of a live
      extrauterine gestation is the only specific sign of such a pregnancy. A small
      number of ectopic pregnancies are interstitial or cornual pregnancies. Rupture of
      an intramural ectopic pregnancy is a serious clinical complication. Diagnosis of
      this ectopic pregnancy can sometimes be made using 2-dimensional transvaginal
      ultrasound (TVS), but it may also require 3-dimensional TVS. We present the case
      of a 25-year-old gravida 0, para 0 woman with amenorrhea lasting 6(+5) weeks.
      Previous surgery included a right adnexectomy for torsion of a right dermoid
      cyst. The patient's serum hCG was elevated. TVS provided a detailed view of the
      endometrial cavity. The results of 2-dimensional TVS suggested the presence of an
      ectopic pregnancy. The sonogram showed a gestational sac with an embryonic pole
      and a yolk sac, which was separated from the endometrium. Use of 3-dimensional
      TVS demonstrated a live embryo in a gestational sac surrounded by myometrium
      below the right cornu lying outside the endometrium. This finding was confirmed
      by laparotomy and the conceptus was excised. The patient had an uneventful
      postoperative course and was discharged 7 days after surgery. In our case, the
      previous adnexectomy was an identifiable risk factor. Nonetheless, making a
      diagnosis of an intramural pregnancy was challenging. Suspicion may arise when
      sonography has revealed an intramural gestational sac.

PMID- 15856518
TI  - Prenatal sonographic diagnosis of truncus arteriosus associated with
      holoprosencephaly.
AB  - We present the case of a truncus arteriosus associated with holoprosencephaly
      detected in a fetus in the first trimester and the sonographic findings that
      established this diagnosis. A physical exam was performed on a 35-year-old
      pregnant woman, gravida 2, para 1. At 20 weeks, sonography showed large-for-date
      uterine size. Fetal biometry was consistent with menstrual age. Amniotic fluid
      volume was elevated to 25 AFI cm. Fetal echocardiography revealed a single common
      artery arising from the heart, a ventricular septal defect, and other cardiac
      defects. Abnormalities of the fetal brain and face were also shown via
      sonography, including the presence of a common lateral ventricle without falx
      cerebri. Alobar holoprosencephaly, the most severe form of holoprosencephaly, was
      diagnosed. Prenatal chromosomal analysis was offered and the patient elected to
      have cordocentesis. The chromosome study was normal. Success in surgical repair
      of truncus arteriosus is established, but alobar holoprosencephaly is associated
      with neonatal death. Continuation of the pregnancy carried risks for the mother.
      After proper counseling, the parents of this fetus were offered and accepted
      termination of pregnancy. A male abortus weighing 320 grams was delivered.
      Postnatal findings and autopsy confirmed the diagnosis.

PMID- 15856519
TI  - Sonography as the primary screening method in evaluating blunt abdominal trauma.
AB  - PURPOSE: The radiological evaluation of patients with blunt abdominal trauma can
      be done with either ultrasound (US) or computed tomography (CT) with strategies
      varying considerably among institutions. We evaluated the efficacy of our current
      strategy in which US is used at our hospital as the primary screening tool for
      patients with blunt abdominal trauma. METHODS: We retrospectively analysed all
      patients admitted to our hospital with possible blunt abdominal trauma who
      underwent abdominal US, abdominal CT and/or a laparotomy during the initial
      trauma assessment from 1998 until 2002 (n = 1149). RESULTS: Nine-hundred sixty
      one of the 1149 patients had a negative US, of which 922 were true negative,
      resulting in a negative predictive value of 96%. A CT of the abdomen was
      performed in 7%. In 1.7% there was delayed diagnosis with no significant
      additional morbidity. Fourteen of the 103 laparotomies (14%) were non
      therapeutic; in 5 of these cases the patients underwent non-therapeutic
      laparotomy despite the performance of a CT. Seven were emergency operations.
      CONCLUSIONS: In our practice, the use of US for the evaluation of acute blunt
      abdominal trauma is adequate, with a high negative predictive value, a small
      number of delayed diagnoses, and an acceptable rate of non-therapeutic
      laparotomies.

PMID- 15856520
TI  - The role of sonography in detecting radial head subluxation in a child.
AB  - Injuries around the elbow joint in children can be difficult to diagnose on the
      basis of findings on physical examination and radiographs. We present the case of
      a 4-year-old girl with a probable subluxation of the radial head, based on the
      findings on physical examination and radiographs. Radiography raised the
      possibility of a radial head subluxation. Sonography demonstrated displacement of
      the cartilaginous head of the radius away from the capitellum in the affected
      elbow. The child underwent corrective surgery. During fluoroscopy, results of an
      ulnar stress test were positive for lateral ligament tears. The patient's arm was
      put in a cast for 6 weeks. At 1-year follow-up, the patient had full range of
      motion of the elbow without pain. We present the findings of sonographic studies
      used to confirm the diagnosis.

PMID- 15856521
TI  - Conservation of helicity and helical character matching in chiral interactions.
AB  - An electronic theory for molecular chirality and chiral interactions has recently
      been published that suggests that underlying chiral interactions is the
      conservation of molecular electronic helicity and that enantioselectivity in a
      reaction can be maximized when the interacting chiral components are helically
      matched. Herein are presented proofs for these principles, and their connections
      with other theories and implications for the design of chiral catalysts are
      discussed.

PMID- 15856522
TI  - Experimental study and simplified mathematical description of preferential
      crystallization.
AB  - The purpose of this paper is to investigate the concept of preferential
      crystallization, with a focus on aspects of quantification and application from
      an engineering point of view. The amino acid threonine was used as a model system
      in the experiments performed. Application of on-line polarimetry in combination
      with measurements of an on-line density meter proved the general applicability of
      this method in order to monitor directly the resolution progress, to recognize
      the region of "safe" resolution, and to gain information about the
      crystallization kinetics. For evaluation of the crystal growth kinetics of the
      desired enantiomers, the method of moments was applied to analyze isothermal
      single-step crystallization experiments. A population balance model is used in
      order to simulate the time changes of liquid-phase composition during the
      preferential crystallization process. Finally, preliminary experimental results
      regarding the cyclic operation mode are presented.

PMID- 15856523
TI  - Vibrational spectroscopic studies to acquire a quality control method of
      Eucalyptus essential oils.
AB  - This article presents a novel and original approach to analyze in situ the main
      components of Eucalyptus oil by means of Raman spectroscopy. The obtained two
      dimensional Raman maps demonstrate a unique possibility to study the essential
      oil distribution in the intact plant tissue. Additionally, Fourier Transform (FT)
      Raman and attenuated total reflection (ATR)-IR spectra of essential oils isolated
      from several Eucalyptus species by hydrodistillation are presented. Density
      Functional Theory (DFT) calculations were performed in order to interpret the
      spectra of the essential oils of the Eucalyptus species. It is shown that the
      main components of the essential oils can be recognized by both vibrational
      spectroscopic techniques using the spectral information of the pure terpenoids.
      Spectroscopic analysis is based on the key bands of the individual volatile
      substances and therefore allows one to discriminate different essential oil
      profiles of several Eucalyptus species. It has been found that the presented
      spectroscopic data correlate very well with those obtained by gas chromatography
      (GC) analysis. All these investigations are helpful tools to generate a fast and
      easy method to control the quality of the essential oils with vibrational
      spectroscopic techniques in combination with DFT calculations.

PMID- 15856524
TI  - Chiral discrimination of secondary alcohols by both 1H-NMR and HPLC after
      labeling with a chiral derivatization reagent, 2-(2,3
      anthracenedicarboximide)cyclohexane carboxylic acid.
AB  - Enantiomeric discrimination of chiral secondary alcohols was performed by both
      reversed-phase HPLC and 1H-NMR after labeling with a chiral fluorescent
      derivatization reagent, 2-(2,3-anthracenedicarboximide)cyclohexanecarboxylic
      acid. It was possible to discriminate by HPLC the chirality of alcohols up to C30
      having a chiral hydroxyl group at the middle of the straight alkyl chain, and, by
      1H-NMR, alcohols up to C16. For alcohols having one straight alkyl and one
      isoalkyl group with the same carbon numbers at both sides of a hydroxyl group, it
      was possible to discriminate the chiralities of alcohols up to C19 by both 1H-NMR
      and HPLC. The 1H-NMR methods also made it possible to determine absolute
      configurations empirically.

PMID- 15856525
TI  - Human relevance of rodent prolactin-induced non-genotoxic mammary carcinogenesis:
      prolactin involvement in human breast cancer and significance for toxicology risk
      assessments.
AB  - Prolactin-induced mammary carcinogenesis in rodents, particularly rats, is often
      stated to be of low toxicological relevance to humans. This opinion appears to
      have developed from a number of lines of cited evidence. Firstly, there had been
      long experience of use of dopamine antagonists (that increase prolactin) in human
      medicine and no evidence of an increase in breast cancer incidence or risk had
      been reported. Secondly, dopamine agonists (that lower prolactin) had been shown
      to have no effect in human breast cancer treatment. Thirdly, the actions of
      prolactin were considered different between rodents and humans. However, recent
      evidence now suggests that prolactin has a major role in human breast cancer, and
      the similarity of mechanism with the rodent suggests that prolactin-mediated
      mammary carcinogenesis in rodents could be of much higher toxicological relevance
      to humans than previously thought. Large epidemiology studies have upgraded a
      limited database and shown that dopamine antagonists (both antipsychotics and
      anti-emetics) increase breast cancer risk, that hyperprolactinaemia is
      consistently associated with human breast cancer growth, development and poor
      prognosis, and that prolactin is indeed a mitogen in human breast cancer cells
      that suppresses apoptosis and upregulates BRCA1. It is now clear that initial
      studies giving dopamine agonists to breast cancer patients had no effect because
      breast cancer cells also produced prolactin independently of the pituitary, which
      remained uncontrolled and unrecognized in early clinical studies. The evidence
      for the role of prolactin in human breast cancer is now strong and consistent,
      and is discussed and related to the risk assessment of drugs and chemicals. The
      conclusion is that it is invalid to suggest that prolactin-induced mammary
      carcinogenesis in rodents is of low relevance to humans because prolactin can
      induce an adverse response in the mammary tissue of both rodents and humans
      alike. Drugs and chemicals causing rodent prolactin-induced mammary
      carcinogenesis may therefore pose a risk to humans via the same mechanism if
      exposures also increase prolactin secretion in humans.

PMID- 15856526
TI  - Roles for USF-2 in lung cancer proliferation and bronchial carcinogenesis.
AB  - The upstream stimulatory factors USF-1 and USF-2 dimerize to regulate
      transcription through E-box motifs in target genes. Although widely expressed,
      they can mediate tissue-specific transcription and we previously reported that
      USF-2 can enhance transcription of arginine vasopressin, a neuropeptide growth
      factor in small cell lung cancer. Here we determine the expression and role of
      USF-2 in lung cancer subtypes and examine USF-2 distribution in the bronchial
      epithelium. For a panel of 12 cell lines and 10 frozen human tumour samples,
      immunoblotting demonstrated that USF-2 expression was more frequent and abundant
      in small cell lung cancer than in non-small cell lung cancer. An
      immunohistochemical study of 108 formalin-fixed and paraffin-embedded human
      samples was undertaken to localize USF-2 expression and included 44 small cell
      and 32 non-small cell lung cancers, and 32 samples with bronchial dysplasia. USF
      2 was restricted to ciliated cells in normal bronchial epithelium, but was more
      strongly expressed in dysplastic epithelium (72%) and certain lung cancer types,
      including small cell lung cancer (71%), squamous cell carcinoma (69%) and a large
      cell neuroendocrine carcinoma, but was less common in adenocarcinoma (11%). In a
      small series, expression was assessed adjacent to positively staining tumours; in
      phenotypically normal bronchial tissues, USF-2 was more highly expressed at 1 cm
      than at 5 cm from the tumour. Transient USF-2 overexpression in non-small cell
      lung cancer cell lines significantly stimulated in vitro cell proliferation; this
      response was most apparent for NCI-H460 (p < 0.005), reducing the mean cell
      doubling time from 19 to 16 h. Dominant-negative USF-2 mutants had no significant
      effect on cell growth. Taken together, these data suggest that USF-2 represents a
      relatively early molecular marker for the development of bronchial dysplasia and
      non-adenocarcinoma lung cancer. USF may also play a role in bronchial
      carcinogenesis, perhaps through promoting cell proliferation, although the genes
      through which this is regulated remain to be determined.

PMID- 15856527
TI  - Bis[2-(dimethylamino)ethyl]ether(CH3)2NCH2CH2OCH2CH2N(CH3)2.

PMID- 15856528
TI  - Effects of bismuth citrate on the viability and function of Leydig cells and
      testicular macrophages.
AB  - Bismuth is present in several popular over-the-counter drugs for nausea and
      diarrhea and is occasionally abused by patients with chronic gastrointestinal
      disorders. The most common consequence of bismuth overdose is neurological
      dysfunction. In experimental animals, bismuth overdose results in lowered serum
      testosterone levels, suggesting that reproductive dysfunction may be an
      additional component of bismuth toxicity. Although the precise mechanisms
      responsible for the lowered testosterone levels are unknown, it has been shown
      that bismuth accumulates within testicular macrophages. This may be important
      because these cells, which are commonly found in direct contact with Leydig
      cells, are known to exert paracrine influences on the Leydig cells for local
      control of testosterone production. However, bismuth may also exert direct
      effects on Leydig cells because it passes by these cells on its way to the
      phagocytic macrophages. The purpose of the present studies was to isolate both
      testicular macrophages and Leydig cells from rat testis and study the direct
      effects of bismuth on these cells with regard to their viability and function. We
      found that when Leydig cells were treated for 24 h with bismuth (1-100 microM) no
      change in viability or secretion of testosterone was observed. However, when
      testicular macrophages were similarly treated with bismuth a significant effect
      on viability was observed with as little as 6.25 microM bismuth, with near
      complete cell death at 50 microM after 24 h. However, bismuth had no effect on
      the viability on testicular macrophages at 50 microM up to 8 h, therefore, we
      studied the secretion of tumor necrosis factor alpha (TNF-alpha) after 4 h of
      exposure to 50 microM bismuth and found no influence on the production of TNF
      alpha. Taken together, it seems likely that bismuth has no direct effects on
      Leydig cells but, rather, lowers testosterone levels by killing testicular
      macrophages, thereby interrupting their local paracrine influence on Leydig cells
      through factors other than TNF-alpha.

PMID- 15856529
TI  - Antioxidant property of Nigella sativa (black cumin) and Syzygium aromaticum
      (clove) in rats during aflatoxicosis.
AB  - Aflatoxins, a group of closely related, extremely toxic mycotoxins produced by
      Aspergillus flavus and A. parasiticus, can occur as natural contaminants of foods
      and feeds. Aflatoxins have been shown to be hepatotoxic, carcinogenic, mutagenic
      and teratogenic to different animal species. Nigella sativa (black cumin) and
      Syzygium aromaticum (clove) oil are used for the treatment of inflammatory
      diseases and have antioxidant properties. The aim of this study was to
      investigate the ability of these volatile oils to scavenge free radicals
      generated during aflatoxicosis. Sixty male rats were divided into six treatment
      groups, including a control group, and the groups were treated for 30 days with
      Nigella sativa and Syzygium aromaticum oils with or without aflatoxin. Blood
      samples were collected at the end of the experimental period for haematological
      and biochemical analysis. The results indicated that exposure to aflatoxins
      resulted in haematological and biochemical changes typical for aflatoxicosis.
      Treatment with Nigella sativa and Syzygium aromaticum oil of rats fed an
      aflatoxin-contaminated diet resulted in significant protection against
      aflatoxicosis. Moreover, Nigella sativa oil was found to be more effective than
      Syzygium aromaticum oil in restoring the parameters that were altered by
      aflatoxin in rats.

PMID- 15856530
TI  - Effect of anaesthetics[sol ]terminal procedures on neurotransmitters from non
      dosed and aroclor 1254-dosed rats.
AB  - Subtle effects of low-dose exposure to environmental toxicants may be altered or
      masked by an inappropriate choice of anaesthesia prior to manipulation or
      termination of experimental animals. This study was designed to investigate
      effects of various anaesthetics and terminal procedures on neurotransmitters from
      male Sprague-Dawley rats. Significant changes in neurotransmitters were observed
      in the caudate nucleus, nucleus accumbens, hippocampus and substantia nigra but
      not the frontal cortex upon exposure to isoflurane, an Equithesin-like mixture or
      carbon dioxide relative to control animals that were decapitated without
      anaesthesia. Terminal use of any of these three anaesthetics also masked or
      altered some of the changes induced by exposure to Aroclor 1254. These results
      suggest that it is critical to avoid anaesthetizing experimental animals and that
      decapitation is the preferred method for euthanasia when conducting neurochemical
      studies.

PMID- 15856532
TI  - Developmental toxicity study with 3-(methylthio)propionaldehyde vapor by whole
      body exposure of Sprague-Dawley rats.
AB  - Time-mated Sprague-Dawley rats were exposed whole body to analytically measured 3
      (methylthio) propionaldehyde (3-MTP) vapor concentrations of 0 (air controls),
      9.87, 58.3 and 127.8 ppm over gestational days (gd) 6-15 for 6 h day(-1). There
      was an exposure concentration-related maternal toxicity (clinical signs, body
      weight change and food consumption) that was marginal at 9.87 ppm. No effects on
      gestational parameters, fetal numbers and sex ratio or fetal body weights were
      noted. There was no increase in the incidence of either malformations or
      variations (total, external, visceral or skeletal). Thus, the no-observed-adverse
      effect level (NOAEL) for development toxicity for exposure to 3-MTP vapor was
      127.8 ppm.

PMID- 15856531
TI  - 2-Ethyl-1,3-hexanediol.

PMID- 15856533
TI  - Investigation into possible DNA damaging effects of ultrasound in occupationally
      exposed medical personnel--the alkaline comet assay study.
AB  - In the present paper the possible DNA damaging effects of ultrasound in
      occupationally exposed medical personnel were investigated using the alkaline
      comet assay. The extent of DNA migration in peripheral blood leucocytes was
      measured. Parameters of the comet assay were studied in 30 medical workers
      occupationally exposed to ultrasound and in 30 corresponding unexposed control
      subjects. It was found that the subjects who were occupationally exposed to
      ultrasound for various periods of time showed a highly significant increase in
      levels of DNA damage compared with the control. The results obtained have
      confirmed the usefulness of the alkaline comet assay as a sensitive biodosimetric
      method, reflecting the current level of DNA damage and/or repair in peripheral
      blood leucocytes of ultrasound-exposed subjects. In spite of their limitations,
      the results of the present investigation indicate that individuals occupationally
      exposed to ultrasound may experience an increased genotoxic risk, emphasizing the
      need for more research into the nature and extent of the biological consequences
      to medical personnel working with ultrasonic equipment.

PMID- 15856535
TI  - EDit: a computer program to assist in the presentation of energy-dependent mass
      spectra.

PMID- 15856534
TI  - Effects of an ethanol-gasoline mixture: results of a 4-week inhalation study in
      rats.
AB  - The inhalation toxicity of an ethanol-gasoline mixture was investigated in rats.
      Groups of 15 male and 15 female rats were exposed by inhalation to 6130 ppm
      ethanol, 500 ppm gasoline or a mixture of 85% ethanol and 15% gasoline (by
      volume, 6130 ppm ethanol and 500 ppm gasoline), 6 h a day, 5 days per week for 4
      weeks. Control rats of both genders received HEPA/charcoal-filtered room air. Ten
      males and ten females from each group were killed after 4 weeks of treatment and
      the remaining rats were exposed to filtered room air for an additional 4 weeks to
      determine the reversibility of toxic injuries. Female rats treated with the
      mixture showed growth suppression, which was reversed after 4 weeks of recovery.
      Increased kidney weight and elevated liver microsomal ethoxyresorufin-O
      deethylase (EROD) activity, urinary ascorbic acid, hippuric acid and blood
      lymphocytes were observed and most of the effects were associated with gasoline
      exposure. Combined exposure to ethanol and gasoline appeared to exert an additive
      effect on growth suppression. Inflammation of the upper respiratory tract was
      observed only in the ethanol-gasoline mixture groups, and exposure to either
      ethanol and gasoline had no effect on the organ, suggesting that an irritating
      effect was produced when the two liquids were mixed. Morphology in the adrenal
      gland was characterized by vacuolation of the cortical area. Although
      histological changes were generally mild in male and female rats and were
      reversed after 4 weeks, the changes tended to be more severe in male rats. Brain
      biogenic amine levels were altered in ethanol- and gasoline-treated groups; their
      levels varied with respect to gender and brain region. Although no general
      interactions were observed in the brain neurotransmitters, gasoline appeared to
      suppress dopamine concentrations in the nucleus accumbens region co-exposed to
      ethanol. It was concluded that treatment with ethanol and gasoline, at the levels
      studied, produced mild, reversible biochemical hematological and histological
      effects, with some indications of interactions when they were co-administered.

PMID- 15856536
TI  - Characterization of oxygenated derivatives of isoprene related to 2-methyltetrols
      in Amazonian aerosols using trimethylsilylation and gas chromatography/ion trap
      mass spectrometry.
AB  - In the present study, we have tentatively identified the structures of three
      oxygenated derivatives of isoprene in Amazonian rain forest aerosols as the C(5)
      alkene triols, 2-methyl-1,3,4-trihydroxy-1-butene (cis and trans) and 3-methyl
      2,3,4-trihydroxy-1-butene. The formation of these oxygenated derivatives of
      isoprene can be explained by acid-catalyzed ring opening of epoxydiol derivatives
      of isoprene, namely, 1,2-epoxy-2-methyl-3,4-dihydroxybutane and 1,2-dihydroxy-2
      methyl-3,4-epoxybutane. The structural proposals of the C(5) alkene triols were
      based on chemical derivatization reactions and detailed interpretation of
      electron and chemical ionization mass spectral data, including data obtained from
      first-order mass spectra, deuterium labeling of the trimethylsilyl methyl groups,
      and MS(2) ion trap experiments. The characterization of 2-methyl-1,3,4-trihydroxy
      1-butene (cis and trans) and 3-methyl-2,3,4-trihydroxy-1-butene in forest
      aerosols is important from an atmospheric chemistry viewpoint in that these
      compounds hint at the formation of intermediate isomeric epoxydiol derivatives of
      isoprene and as such provide mechanistic insights into the formation of the
      previously reported 2-methyltetrols through photooxidation of isoprene.

PMID- 15856537
TI  - A 56-year-old woman with fever, generalized body aches, and anemia after a tick
      bite.

PMID- 15856538
TI  - JH6 gene usage among HCV-associated MALT lymphomas harboring t(14;18)
      translocation.

PMID- 15856539
TI  - [Classification of mammographic results].

PMID- 15856540
TI  - Reversing the failures of Roll Back Malaria.

PMID- 15856542
TI  - EU plans to boost research.

PMID- 15856541
TI  - Newborn screening report sparks debate in USA.

PMID- 15856543
TI  - The CERRIE majority and minority reports and the COMARE response.

PMID- 15856544
TI  - Reflections on CERRIE.

PMID- 15856545
TI  - LNT hypothesis, thresholds and hormesis.

PMID- 15856546
TI  - Radioactive waste management.

PMID- 15856547
TI  - When clinical practice guidelines fail.

PMID- 15856548
TI  - Getting Africa on the front page.

PMID- 15856549
TI  - Bibliography. Current world literature. Urolithiasis.

PMID- 15856550
TI  - Regionalization of the isthmic and cerebellar primordia.
AB  - The complex migrations of neurons born in the dorsal neural tube of the isthmic
      and rhombomere l (rl) domains complicate the delineation of the cerebellar
      primordium. We show that Purkinje cells (P) are likely generated over a wide
      territory before gathering in the future cerebellar primordium under the
      developing external granular layer. Later expansion of the cerebellum over a
      restricted ependymal domain could rely on mutual interations between P cells and
      granule cell progenitors (GCP). P are attracted by GCP and in turn stimulate
      their proliferation, increasing the surface of the developing cortex. At later
      stages, regionalization of the developing and adult cerebellar cortex can be
      detected through regional variations in the distribution of several P cell
      markers. Whether and how the developmental and adult P subtypes are related is
      still unknown and it is unclear if they delineate the same sets of cerebellar
      subdivisions. We provide evidence that the early P regionalization is involved in
      intrinsic patterning of the cerebellar primordium, in particular it relate to the
      organization of the corticonuclear connection. We propose that the early P
      regionalization provides a scaffold to the mature P regionalization but that the
      development of functional afferent connections induces a period of P plasticity
      during which the early regional identity of P could be remodeled.

PMID- 15856551
TI  - Software spinoff. Physician-executives form new company.

PMID- 15856552
TI  - Preoperative evaluation and risk factors of lung cancer.
AB  - Based on a review of the literature on resectable lung cancer, pulmonary risk
      factors before, during and after surgery are discussed. The role of preoperative
      evaluation in order to determine the patient ability to withstand radical
      resection is considered. Spirometric indexes as forced expired volume (FEV1) and
      diffusing lung carbon monoxide capacity (DLCO) should be measured first. If FEV1
      and DLCO are > 60% of predicted, patients are at low risk for complications and
      can undergo pulmonary resection. However, if FEV1 and DLCO are <60% of predicted,
      further evaluation with a quantitative lung scan is required. If predicted
      postoperative values for FEV1 and DLCO are >40%, patients can undergo lung
      resection, otherwise exercise testing is necessary. If the latter shows maximal
      oxygen uptake (VO2max) of > 15ml/Kg, surgery can be performed; if VO2max is <15
      ml/Kg, patients are inoperable.

PMID- 15856553
TI  - [Spectral analysis of dissolved organic matter derived from rice straw after
      chemical treatment].
AB  - Fourier transform infrared spectroscopy (FTIR), ultraviolet spectroscopy (UV),
      and nuclear magnetic resonance spectroscopy (NMR) were used to study the chemical
      composition of Dissolved Organic Matter (DOM) derived from rice straw in the
      hydrolysis process with a dilute complex acid solution. The results obtained are
      as follows. FTIR spectra could indicate the changes of DOM during the hydrolysis
      process of rice straw. With the progress of rice straw hydrolysis, methyl,
      methylene, aromatic compounds and carbohydrates decreased, most of aliphatic
      compounds were oxidized to CO2 and H2O, and others were turned into carbonates.
      Most of the organic silicon was hydrolyzed into inorganic silicon. The proteins,
      amino acids and other nitrogen were hydrolyzed to NH4+. All the recalcitrant
      fractions of rice straw, such as hemi-cellulose, cellulose and silicon sharply
      decreased during the process of chemical treatment. The results obtained in this
      paper proposed that the changes of DOM of rice straw in the hydrolysis could be
      an indication in the changes of chemical composition of rice straw during the
      hydrolyzation, and FTIR, UV and NMR were good methods to study the changes in the
      structure of organic compounds.

PMID- 15856555
TI  - Response of a Si-diode-based device to fast neutrons.
AB  - Semiconductor devices based on a Si-detector are frequently used for charged
      particle's detection; one application being in the investigation of cosmic
      radiation fields. From the spectra of energy deposition events in such devices,
      the total energy deposited by the radiation in silicon can be derived. This
      contribution presents the results of studies concerning the response of this type
      of detector to fast neutrons. First, the spectrum of energy deposition was
      established in fast neutron radiation fields with average energies from 0.5 to 50
      MeV. It was found that these spectra vary significantly with the neutron energy.
      The comparison with the spectra registered in photon beams permitted an
      estimation of the part of energy deposited that could be attributed to neutrons.
      It was found that this part increases rapidly with neutron energy. The
      possibilities to use this type of detector for neutron detection and dosimetry
      for radiation protection are analysed and discussed.

PMID- 15856554
TI  - Forecasting changes in amphibian biodiversity: aiming at a moving target.
AB  - Amphibian population declines and sudden species' extinctions began to be noted
      at the beginning of the 1980s. Understanding the causes of the losses is hampered
      by our poor knowledge of the amphibian fauna in many parts of the world.
      Amphibian taxa are still being described at a high rate, especially in the
      tropics, which means that even quantifying species lost as a percentage of the
      current fauna can be a misleading statistic in some parts of the globe. The
      number of species that have gone missing is only one measure of the loss of
      biodiversity. Long-term studies of single-species populations are needed, but
      this approach has its limits. Amphibian populations often show great annual
      variation in population size making it difficult, if not impossible, to use short
      term studies as a basis for deciding if a population is increasing or decreasing
      in the long term. Aggregating single studies into databases and searching for
      patterns of variation is a way of overcoming this limitation. Several databases
      on species and population time series are available or in development. These
      records show that declines are continuing worldwide with some species and
      populations, especially in the tropics and at higher elevations, at greater risk
      of extinction than others. Unfortunately, amphibian databases with population
      time series have much less information for the tropics compared to the temperate
      zone, and less for Africa and Asia compared with Europe and North America.
      Focusing limited resources using comprehensive statistical designs is a way to
      maximize the efficiency and effectiveness of monitoring efforts. It is clear
      that, in the first decades of the twenty-first century, the regions of the globe
      with the highest diversity of amphibian species will experience the greatest
      rates of decrease of forests and increase in human population size, fertilizer
      use, agricultural production, creation of new croplands and irrigation. Many of
      these changes are likely negatively to affect amphibian species diversity, and
      their influence must be understood before concluding, at least for amphibians,
      that the 2010 millennium assessment goal of significantly reversing the rate of
      loss of Earth's biodiversity can be met.

PMID- 15856556
TI  - Radiation measurement on the International Space Station.
AB  - The results of an investigation of radiation environment on board the ISS with
      apogee/perigee of 420/380 km and inclination 51.6 degrees are presented. For
      measurement of important characteristics of cosmic rays (particles fluxes, LET
      spectrum, equivalent doses and heavy ions with Z > or = 2) a nuclear photographic
      emulsion as a controllable threshold detector was used. The use of this detector
      permits a registration of the LET spectrum of charged particles within wide range
      of dE/dx and during the last years it has already been successfully used on board
      the MIR station, Space Shuttles and "Kosmos" spacecrafts. An integral LET
      spectrum was measured in the range 0.5-2.2 x 10(3) keV/micrometers and the value
      of equivalent dose 360 microSv/day was estimated. The flux of biologically
      dangerous heavy particles with Z > or = 2 was measured (3.85 x 10(3)
      particles/cm2).

PMID- 15856557
TI  - Radiation exposure at ground level by secondary cosmic radiation.
AB  - The contribution of the charged component of secondary cosmic radiation to the
      ambient dose equivalent H*(10) at ground level is investigated using the muon
      detector MUDOS and a TEPC detector surrounded by the coincidence detector CACS to
      identify charged particles. The ambient dose equivalent rate H*(10)T as measured
      with the TEPC/CACS is used to calibrate the MUDOS count rate in terms of H*(10).
      First results from long-term measurements at the PTB reference site for ambient
      radiation dosimetry are reported. The air pressure corrected dose rate shows, as
      expected, a strong correlation with the neutron count rate as measured with the
      Kiel neutron monitor. The measured seasonal variations exhibit a negative
      correlation with the temperature changes in the upper layers of the atmosphere
      where the ground level muons are produced.

PMID- 15856558
TI  - Small step or giant leap? Human locomotion on Mars.
AB  - Human locomotion on Mars will be considerably different from on Earth. Optimum
      walking speeds will be approximately 30% lower and transitioning from a walk to a
      run will occur at a speed 25% slower. Peak vertical forces will be reduced by as
      much as 50%, and although ground contact time will remain constant with
      locomotion in 1 g, stride length and stride time will increase. During running on
      Mars airborne time will increase by approximately 80% in comparison to running on
      the Earth. On Mars, half as much energy will be required to travel the equivalent
      distance on Earth and it will be 65% more economical to run rather than to walk.
      Crews will, therefore, find themselves using a loping gait--a running-like
      action, with a slight upper body lean and an extended aerial phase, an unfamiliar
      gait in terrestrial locomotion.

PMID- 15856559
TI  - Water related environment modelling on Mars.
AB  - During a human Mars exploration because of the lack of time astronauts need fast
      methods for the interpretation of unexpected observations which give them
      flexibility and new, important targets. With in-situ modelling it is possible to
      get information on various past and present processes at the same location on a
      far wider spectrum than would be realized even during a long mission. This work
      summarizes the potential technical requirements and benefits of the modelling.
      Based on a simple estimation with a 300 kg package, and 1-10% of the working time
      of 1-2 astronauts at the same location, they can get plenty of new and important
      information for the whole past and present Mars. With the proposed five test
      groups astronauts will be able to make better and newer kinds of interpretations
      of observations, and find better targets and methods during the same mission.

PMID- 15856560
TI  - Francis H. C. Crick (1916-2004).

PMID- 15856561
TI  - "Who shall live...": a report from the CCAR Task Force on Assisted Suicide.

PMID- 15856562
TI  - Epilepsy after the Decade of the Brain: misunderstandings, challenges, and
      opportunities.

PMID- 15856563
TI  - The ethics of chimeras and hybrids: dignity and original solitude.

PMID- 15856564
TI  - On "vegetative" human beings.

PMID- 15856565
TI  - A new ESR dosimeter based on bioglass material.
AB  - Bioglass (Bio-G) samples were irradiated with 60Co gamma-rays to study radicals
      for dosimetric materials with electron spin resonance (ESR). The ESR spectrum of
      Bio-G is characterized by two main signals. The first signal at g approximately =
      4.3 corresponds to Fe3+ impurities and the second signal at g approximately =
      2.0130 with line-width 10.85 G is ascribed as a hole center. The gamma-ray dose
      response and thermal stability were studied to establish the suitability of
      bioglass as an ESR dosimeter. A radical formation efficiency, G-value, of 0.53 +/
      0.11 was obtained. The lifetime of radicals and the activation energy were
      estimated from Arrhenius plots to be approximately 255 +/- 46 days and 0.71 eV,
      respectively.

PMID- 15856566
TI  - University uses "implied informed consent".

PMID- 15856567
TI  - Congressmen say military should have the right to informed consent.

PMID- 15856568
TI  - The PVS patient.

PMID- 15856569
TI  - Effect of high-dose irradiation on the optically stimulated luminescence of
      Al2O3:C.
AB  - This paper examines the effect of high-dose irradiation on the optically
      stimulated luminescence (OSL) of Al2O3:C, principally on the shape of the OSL
      decay curve and on the OSL sensitivity. The effect of the degree of deep trap
      filling on the OSL was also studied by monitoring the sensitivity changes after
      doses of beta irradiation and after step-annealing of samples previously
      irradiated with high doses. The OSL response to dose shows a linear-supralinear
      saturation behavior, with a decrease in the response for doses higher than those
      required for saturation. This behavior correlates with the sensitivity changes
      observed in the samples annealed only to 773 K, which show sensitization for
      doses up to 20-50 Gy and desensitization for higher doses. Data from the step
      annealing study leads to the suggestion that the sensitization is caused by the
      filling of deep electron traps, which become thermally unstable at 1100-1200 K,
      whereas the desensitization is caused by the filling of deep hole traps, which
      become thermally unstable at 800-875 K, along with a concomitant decrease in the
      concentration of recombination centers (F+ -centers). Changes in the shape of the
      OSL decay curves are also observed at high doses, the decay becoming faster as
      the dose increases. These changes in the OSL decay curves are discussed in terms
      of multiple overlapping components, each characterized by different
      photoionization cross-sections. However, using numerical solutions of the rate
      equations for a simple model consisting of a main trap and a recombination
      center, it is shown that the kinetics of OSL process may also be partially
      responsible for the changes in the OSL curves at high doses in Al2O3:C. Finally,
      the implication of these results for the dosimetry of heavy charged particles is
      discussed.

PMID- 15856570
TI  - The human act and medical practice.

PMID- 15856571
TI  - Response of thermoluminescent detectors to charged particles and to neutrons.
AB  - Thermoluminescent detectors (TLDs) are widely used for the dosimetry of photons
      and electrons. They are less used for the radiation with higher linear energy
      transfer (LET). One of the reasons for that is that their TL relative efficiency
      eta decreases for the most of them with increasing LET. The paper presents first
      a review of author's experimental results in which eta was established for
      charged particles having LET of the order from 1 to 100 keV/micrometers in
      tissue. Among TLDs studied were known materials like LiF:Mn; Ti; Al-P glass;
      CaSO4:Dy; Al2O3:Na; and Al2O3:C. It was found that the dependence of their eta on
      LET is not the same for all TLDs studied. The response of the same materials to
      neutrons was also studied. It was found that both eta as the relative response
      (RR) defined in terms of absorbed dose in tissue are different, they depend
      critically also on the composition. When a TLD contains nuclei like 6Li and 10B,
      their RR would be rather high. As far as eta is concerned, the same tendencies
      were observed as for charged particles, i.e. when average LET of secondary
      particles formed in a TLD increases, their eta generally decreases.

PMID- 15856573
TI  - Concluding communique on the "Ethics of biomedical research for a Christian
      vision".

PMID- 15856572
TI  - Long-term physical and psychological health consequences of induced abortion: a
      review of the evidence.

PMID- 15856574
TI  - The response of thermally and optically stimulated luminescence from Al2O3:C to
      high-energy heavy charged particles.
AB  - The thermoluminescence (TL) and optically stimulated luminescence (OSL) response
      of Al2O3 dosimeters to high-energy heavy charged particles (HCP) has been studied
      using the heavy ion medical accelerator at Chiba, Japan. The samples were Al2O3
      single-crystal chips, of the type usually known as TLD-500, and Luxel(TM)
      dosimeters (Al2O3:C powder in plastic) from Landauer Inc. The samples were
      exposed to 4He (150 MeV/u), 12C (400 MeV/u), 28Si (490 MeV/us) and 56Fe (500
      MeV/u) ions, with linear energy transfer values covering the range from 2.26 to
      189 keV/micrometers in water and doses from 1 to 100 mGy (to water). A 90Sr/90Y
      beta source, calibrated against a 60Co secondary standard, was used for
      calibration purposes. For OSL, we used both continuous-wave OSL measurements (CW
      OSL, using green light stimulation at 525 nm) and pulsed OSL measurements (POSL,
      using 532 nm stimulation from a Nd:YAG Q-switched laser). The efficiencies (eta
      HCP, gamma) of the different HCPs at producing OSL or TL were observed to depend
      not only upon the linear energy transfer (LET) of the HCP, but also upon the
      sample type (single crystal chip or Luxel(TM)) and the luminescence method used
      to define the signal--i.e. TL, CW-OSL initial intensity, CW-OSL total area, or
      POSL. Observed changes in shape of the decay curve lead to potential methods for
      extracting LET information of unknown radiation fields. A discussion of the
      results is given, including the potential use of OSL from Al2O3 in the areas of
      space radiation dosimetry and radiation oncology.

PMID- 15856575
TI  - Orthodoxy and the public square: symposium.

PMID- 15856576
TI  - Pre-implantation genetic diagnosis, stem cells and Jewish law.

PMID- 15856577
TI  - Hindu perspectives on genetic enhancements in humans.

PMID- 15856578
TI  - HIPAA: privacy and public good.

PMID- 15856579
TI  - Mediums and messages: an argument against biotechnical enhancement of soldiers in
      the armies of liberal democracies.
AB  - Assuming that one believes that individuals and states can morally defend values,
      beliefs, and institutions with force (in short, that just wars are morally
      possible), one logically wants just combatants to possess the physical, mental,
      and spiritual capacities that will enable them to win the war. On the other hand,
      being a just combatant in a just war does not morally entitle that combatant to
      do anything to win that war. The moral requirement for just combatants to fight
      justly is codified in international law of war and in state-specific legal
      documents such as the United States Uniform Code of Military Justice. While it is
      almost unequivocally clear to soldiers and civilians who soldiers cannot harm in
      the performance of their duties, and why these people are exempt from harm, it is
      less clear what the state itself (assuming throughout the discussion that the
      state is a just combatant in a just war) can morally do to its own soldiers to
      enhance their chances of victory: can the state do anything to soldiers to give
      them an advantage on the field of battle? For United States soldiers and their
      counterparts in most Western liberal democracies, the answer is obviously no.
      Deeply embedded social and cultural norms in Western democracies mandate that the
      state set and enforce rigid lines which drill sergeants and earnest commanders
      cannot cross, even in the name of combat readiness, grounding these norms in
      notion of basic rights appealed to in the U.S. Constitution. In this essay, I
      argue against some types of drug-induced internal biotechnical enhancement of
      soldiers on the grounds that, in the present state of technology, it is not
      reasonable to suppose that the military can perform such enhancement operations
      on soldiers without causing irrevocable psychological damage that would certainly
      and unjustifiably alienate the soldiers from the very society they serve.

PMID- 15856580
TI  - LiF:Mg,Ti (MTT) TL detectors optimised for high-LET radiation dosimetry.
AB  - The properties of LiF:Mg,Ti (distributed as, e.g., TLD-100 or MTS-N), the most
      frequently used thermoluminescent detector, have been optimised for measurements
      of sparsely ionizing radiation (gamma rays), typically encountered in radiation
      protection or clinical dosimetry. However, these detectors need also to be
      applied in conditions of mixed-field dosimetry with a high-LET component, such as
      those encountered in heavy ion beams or in space. At the Institute of Nuclear
      Physics in Krakow a new type of LiF:Mg,Ti detector (named MTT) has been recently
      developed through modification of its dopant composition. This composition is
      intended to increase the detection efficiency after a dose of high-LET radiation.
      The concentration of dopants in the MTT material is: CMg=50 ppm, and CTi=120 ppm,
      i.e. about a three times less of magnesium and about 10 times more of titanium
      content, compared with the standard MTS-N. The MTT TL detectors feature an
      increased relative efficiency to high-LET radiation, which for 5 MeV alpha
      particles is about twice that of standard LiF:Mg,Ti. The response of MTT
      detectors has been studied in charged particle beams of the HIMAC accelerator in
      Chiba, Japan and in Dubna, Russia. The main foreseen application of MTT detectors
      are dose measurements in space. The dose after high-LET exposure can be estimated
      from the difference of the response of MTS and MTT detectors. In the near future
      MTT detectors will be applied in the "Matroshka" experiment. Within this
      experiment a specially constructed human phantom will be exposed in free space
      (outside the International Space Station) for 1 year. The phantom will
      incorporate a few thousand measuring points enabling radiation doses to
      particular organs to be determined.

PMID- 15856581
TI  - Dependence of thermoluminescence response of calcium sulphate activated by
      dysprosium on the temperature irradiation.
AB  - Radiation dosimetry is a very important issue in space research and in
      experiments that try to simulate chemical processes that may occur in cometary
      nucleus, interstellar grains, and other extraterrestrial environments, due to
      their irradiation by cosmic rays. The temperature effect is an important factor
      that has not been considered in many of these experiments. In this work, this
      effect was studied in TLD dosimeters exposed to gamma rays. The irradiations were
      done from 77 to 298 K in a gamma cell unit with a dose rate of 1.0 Gy/s. Results
      obtained for CaSO4:Dy show that there is a considerable effect in the evaluation
      of the dose as function of the irradiation temperature.

PMID- 15856582
TI  - Ethical, legal and social implications of genetic testing.

PMID- 15856583
TI  - Patients' rights in Hungary.

PMID- 15856584
TI  - Dosimetric properties of the newly developed KLT-300 (LiF:Mg,Cu,Na,Si) TL
      detector.
AB  - The dosimetric properties of the newly developed KLT-300 (KAERI LiF:Mg,Cu,Na,Si
      TL detector) in KAERI (Korea Atomic Energy Research Institute) were investigated.
      The sensitivity of the TL detector was about 30 times higher than that of the TLD
      100 by light integration. In the study of the dose linearity of the detector, the
      dose response was very linear up to 10 Gy and a sublinear response was observed
      at higher doses. The energy response of the detector was studied for photon
      energies from 20 to 662 keV. The results show that a maximum response of 1.004 at
      53 keV and a minimum response of 0.825 at 20 keV were observed. The
      reproducibility study for the TL detector was also carried out. The coefficients
      of variation for each detector separately did not exceed 0.016, and for all the
      10 detectors collectively it was 0.0054. IEC Standard requires that the
      coefficient of variation shall not exceed 0.075. So, the reproducibility of this
      new TL detector sufficiently satisfied the IEC requirements. A detection
      threshold of the detector was investigated and found to be 70 nGy by Harshaw 4500
      TLD Reader.

PMID- 15856585
TI  - 'Well enough to execute': the health professional's responsibility to the death
      row inmate.

PMID- 15856586
TI  - Dependence of irradiation temperature in the response of iron salts.
AB  - A potential dosimeter based on aqueous frozen solutions and solid-state salt are
      presented for the evaluation of the energy transferred during the interaction of
      high-energy radiation with matter at low temperature. The foundation of these
      dosimeters, both the solid state and the frozen solutions, is based on the
      measurement of the change of the iron oxidation state. The systems were
      irradiated with gamma radiation at different doses (up to 10 MGy), and at
      different temperatures (from 77 to 298 K). The irradiated samples were analysed
      by UV-spectroscopy and Mossbauer spectroscopy. A theoretical model was developed
      for the chemical reactions system. This model reproduces the experimental effects
      produced by the irradiation in aqueous solutions of ferrous salt. The results
      showed that the response of the dosimeters depends on the irradiation
      temperature. At low-radiation doses, the response was linear. In particular, this
      work can be applied to low-temperature dosimetry can be specially applied to
      simulation experiments of extraterrestrial bodies, as well as in general to space
      research.

PMID- 15856587
TI  - On-line physician-patient care.

PMID- 15856588
TI  - Cataract in the Kingdom of Morocco: indications for surgery and functional
      results.
AB  - AIM: To investigate the results of cataract surgery in different settings in the
      Kingdom of Morocco. METHOD: At four separate health facilities, 100 consecutive
      patients undergoing ECCE cataract extraction for age-related cataract were
      examined pre-operatively and 6-8 weeks post-operative for changes in visual
      acuity. RESULTS: Thirty-four percent of patients (better eye acuity) and 95.5% of
      operated eyes had a visual acuity of less than 3/60 pre-operatively. Six to eight
      weeks post-operatively 84.0% of patients (better eye acuity) and 74.7% of
      operated eyes achieved a visual acuity of 6/18 or better. Of 198 eyes having an
      intraocular lens (IOL) implanted, 87.9% achieved 6/18 and 3.0% were less than
      6/60 post-operatively. Of 202 eyes having cataract surgery without an IOL, 61.7%
      achieved 6/18 and 4.5% were less than 3/60. The proportion of eyes receiving an
      IOL in the 4 centres ranged from 29% to 74%. CONCLUSION: Monitoring the pre and
      post-operative acuity of cataract patients can give useful information on the
      indications for surgery in different settings, the use of IOLs and the visual
      outcome. Implantation of an IOL should be encouraged in all people having
      cataract surgery unless contra-indicated.

PMID- 15856589
TI  - Thoughts on the papal address and MANH: reflections on post-coma
      unresponsiveness.

PMID- 15856590
TI  - Iatrogenic esophageal perforation that may sometimes masquerade as esophageal
      atresia.

PMID- 15856591
TI  - Killing versus allowing to die: examining a critical moral difference.

PMID- 15856592
TI  - A critique of the five wishes: comments in the light of a papal statement.

PMID- 15856593
TI  - Law reform, or DIY suicide.

PMID- 15856594
TI  - How not to argue for abortion rights: fighting for choice is not enough.

PMID- 15856595
TI  - Twenty propositions.

PMID- 15856597
TI  - The long road of eugenics: from Rockefeller to Roe v. Wade.

PMID- 15856598
TI  - International Curriculum Guidelines for Preparing Physical Activity Instructors
      of Older Adults, in collaboration with the Aging and Life Course, World Health
      Organization.

PMID- 15856599
TI  - Ethical issues and approaches in stem cell research: from international insights
      to a proposal.
AB  - In recent years and months, human stem cell research has dominated many
      scientists' interests, the media, public debate, and social policy. This paper
      aims to consider, first, the major scientific data on stem cell research that are
      available. Second, I reflect on them by examining how they shaped policies in
      Europe and the United States. I also point to current changes in policy-making
      concerning the creation of ad hoc committees to address this novel issue and how,
      in a few instances, different ethical positions are part of the documents
      produced. In other words, diverse approaches are not solved but kept in tension.
      Finally, I suggest that the current state of research on human stem cell will
      benefit from an ethics of risk.

PMID- 15856600
TI  - Practicing patients, compassion, and hope at the end of life: mining the passion
      of Jesus in Luke for a Christian model of dying well.
AB  - Four centuries ago, Christian moral theologians addressed the issue of dying by
      turning to scripture and the virtues. This work revives that tradition by showing
      that careful theological reflection upon the nature of Christian patience,
      compassion, and hope illuminates the shape of the Good Death. The author draws
      upon Luke's passion narrative to develop a better understanding of these virtues.
      He also takes up the question of whether Jesus' death can be a model of dying
      well for contemporary Christians. Christians are often advised to look to Jesus
      in his dying as a model for themselves, but this recommendation typically leaves
      unanswered what exactly it is about Jesus' dying that is to be imitated. The
      understanding of patience, compassion, and hope developed here provides a means
      of sorting through this issue.

PMID- 15856601
TI  - Human gene banks.

PMID- 15856602
TI  - Should this 96-year old woman be allowed to die?

PMID- 15856603
TI  - Legal issues in the use of controlled substances in pain management.

PMID- 15856604
TI  - Stem cell research: science, ethics and policy.

PMID- 15856605
TI  - Dialogue: Bioethics in space.

PMID- 15856606
TI  - [Local antibiotic therapy in ENT patients].

PMID- 15856607
TI  - Making babies: will a new UK law stop people donating eggs and sperm?

PMID- 15856608
TI  - Let's preserve proper terminology.

PMID- 15856609
TI  - Proteomics data back up soy health claims.

PMID- 15856610
TI  - NIH standards in proteomics workshop. Proteomics repositories up for debate.

PMID- 15856612
TI  - Impact of the Medicare prescription drug benefit on home- and community-based
      services waiver programs.
AB  - "Dual eligibles" is the term for the 6.4 million low-income, elderly, and
      disabled Americans who are enrolled in both Medicare and Medicaid. With home-and
      community-based services waivers allowed under Section 1915(c) of the Social
      Security Act, many of these individuals are able to live in a home or community
      setting, thereby avoiding institutionalization. Surveying Maryland's 3,180 dual
      eligibles who are enrolled in home-and community-based waiver programs, the
      author finds that the end-of-2005 transfer of prescription drug coverage from
      Medicaid to Medicare under the Medicare Modernization Act of 2003 could put these
      beneficiaries in jeopardy. Maryland's experience is likely to be typical of what
      other states will face. The author recommends a number of federal policy
      remedies, among them allowing 90-day prescriptions, using open or shared
      formularies, and lengthening the enrollment period.

PMID- 15856614
TI  - HIV risk and protection among gay male couples: the role of gay community
      integration.
AB  - This study examined the association between different types of integration in the
      gay community and HIV risk among gay male couples. Previous research linking gay
      community integration and involvement among couples to HIV risk has been
      equivocal. Each partner in 59 gay couples completed a separate anonymous
      questionnaire that assessed two types of social involvement in the gay community,
      assimilation into the gay community, and sexual HIV risk behaviors. We used the
      actor-partner interdependence analysis approach, which maintains the couple as
      the unit of analysis while allowing for tests of within-couple, between-couple,
      actor, and partner effects. Analyses revealed that, controlling for symptoms of
      alcohol problems, going to gay bars and clubs independently predicted more HIV
      risk.

PMID- 15856615
TI  - Gay couples, gay communities, and HIV: challenges for health education.

PMID- 15856616
TI  - Improving access to cardiovascular care.

PMID- 15856617
TI  - Unannounced surveys: what you'll need to do within minutes of JCAHO's arrival.

PMID- 15856618
TI  - Don't ignore the costs for quality resources.

PMID- 15856619
TI  - Communication among caregivers is a key focus.

PMID- 15856620
TI  - Don't be fooled by the illusion of patient safety.

PMID- 15856621
TI  - Are you breaking patient privacy regs with e-mails?

PMID- 15856622
TI  - [Percutaneous coronary intervention].
AB  - The aim of this article was to provide an overview on percutaneous coronary
      intervention and to identify the predictive factors of the outcome. Numerous and
      diverse factors have been associated with interventional treatment that include
      intrinsic stent thrombogenicity and patient-, target lesion-, and procedure
      related issues. Stent design, surface coating and the addition of adjunctive
      pharmacotherapeutic agents may influence the degree of platelet activation. The
      application of drug eluting stents represents a potential landmark event for
      percutaneous vascular treatment because marked reductions in restenosis and
      repeat revascularization rates have been observed with drug eluting stents in
      randomized trials. Every effort should be made to optimize stent size and
      deployment. Periprocedural glycoprotein IIb/IIIa inhibitors should be used for
      complex stent procedures and post-procedural antiplatelet therapy should be
      extended for at least 1 year.

PMID- 15856623
TI  - [Babesia microti and Anaplasma phagocytophilum: two emerging zoonotic pathogens
      in Europe and Hungary].
AB  - Babesia microti and Anaplasma phagocytophilum was recently reported with a
      minimum prevalence of 0.9 and 1.3% in Hungary based on the PCR-sequencing
      analysis of 452 European sheep ticks (Ixodes ricinus). These results and the
      epidemiological data of the neighbouring countries indicate that human cases
      caused by these pathogens may occur in the country. The aim of the present paper
      is to summarise the current knowledge on the morphology, life cycle and
      distribution of B. microti and A. phagocytophilum, and the epidemiology, clinical
      features, diagnosis, treatment and control of babesiosis and granulocytic
      anaplasmosis.

PMID- 15856624
TI  - [Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells].
AB  - Role of R-(-)-deprenyl in adhesion of neuronal and non-neuronal cells. The
      beneficial effect of the anti-parkinsonian monoamine oxidase-B inhibitor, R-(-)
      deprenyl has been shown in a number of different diseases, such as Parkinson's
      and Alzheimer's disease, atherosclerosis or tumor formation. The role of the
      cytoskeleton, the main component of cell adhesion, has been suggested in the
      development of these diseases. Nevertheless, the effect of the drug on cell
      adhesion has never been examined. In the present study, the authors studied the
      effect of R-(-)-deprenyl on cell-cell adhesion of neuronal (PC12, rat
      phaeochromocytoma) and non-neuronal (NIH3T3, NIH3T3/EGFR, NIH3T3/EGFR-e3B1 mouse
      embryo fibroblasts, and 5180 mouse sarcoma) cells using cell association assay. R
      (-)-deprenyl treatment resulted in a cell type- and concentration-dependent
      increase in cell-cell adhesion of PC12 cells, which contain no monoamine oxidase
      B, and we observed the same effect in NIH3T3 cells at concentrations lower than
      those needed for monoamine oxidase-B inhibition. Interestingly, R-(-)-deprenyl
      increased cell-cell adhesion of tumor cell lines as well. The effect of R-(-)
      deprenyl was not reversible during a 24-hour recovery period. At the same time,
      the monoamine oxidase-B inactive isomer of the drug, S-(+)-deprenyl had no effect
      on cell-cell adhesion in PC12 and NIH3T3 cells. In this study, the authors
      described a new, monoamine oxidase-B independent effect of R-(-)-deprenyl on cell
      cell adhesion both in neuronal and non neuronal cells. The authors' results with
      S-(+)-deprenyl suggest that the sterical structure of the drug is an important
      factor of the observed effect, which is probably a consequence of an irreversible
      change in the cells.

PMID- 15856625
TI  - [The use and safety of butamirate containing drops, syrup and depot tablets in
      Hungary].
AB  - INTRODUCTION: Butamirate citrate containing medicines are marketed in Hungary
      since 1991. Every year several hundred thousands of children and adults are
      treated with these pharmaceutical products. Aim of the study was to compare the
      prescription habits with the directions provided in the Summary of Product
      Characteristics and to get an overview on the safety and efficacy of these
      products. METHODS: The study results are based on the evaluation of 3215
      questionnaires provided by 276 general practitioners and pulmonologists having
      medical practice in many regions and the capital of Hungary. Responses were
      included into the evaluation only if the name of the physician, the address and
      type of the practice, the therapeutic indication could be precisely identified
      and if the patient returned for at least one control visit. RESULTS: The main
      therapeutic indication of butamirate was cough due to acute lower respiratory
      tract infections (tracheitis, laryngitis, bronchitis). The treatment interval was
      usually 1-2 weeks. Depot tablets were prescribed according to the Summary of
      Product Characteristics. The doses of syrup and drops were frequently and
      notoriously below the one proposed in the Summary of Product Characteristics. In
      14% of the cases the syrup was prescribed for the treatment of children below 3
      years of age. All three products were regarded as effective. Adverse events
      (nausea, vomiting, diarrhoea, skin exanthemas) were reported at 0.5-1% of the
      patients. CONCLUSIONS: The prescribed average daily doses of drops between the
      ages 1 month-12 years and the syrup between the ages 6-12 years were 20-30% below
      the recommended amounts. In Hungary the butamirate citrate containing medicines
      are regarded to be effective. The adverse events were rare and non-serious.

PMID- 15856626
TI  - [A case of femoral osteomyelitis caused by Lactococcus].
AB  - The authors report on a case of osteomyelitis of the femur, where the causative
      agent was Lactococcus. These bacteria are mainly pathogenic in endocardial
      implants and extremely rare in osteomyelitis. The osteomyelitis was complicated
      with endocarditis, cerebral and pulmonary abscess. In the reported case the
      occurrence of osteomyelitis was similar to bone tumor formation, so there was a
      challenging diagnostic approach. Based upon this case, the diagnostic algorithm,
      the treatment strategy and the outcome of the treatment are reported. Authors
      also give a short overview of the literature published on this rare microorganism
      in bone and joint diseases.

PMID- 15856627
TI  - Effects of iohexol on ventilatory functions in patients undergoing diagnostic
      coronary angiography.
AB  - BACKGROUND AND OBJECTIVES: Adverse respiratory reactions have been reported with
      intravascular radiographic contrast media. The aim of the present study is to
      assess the effects of iohexol on pulmonary functions in patients undergoing
      diagnostic coronary angiography (CA). MATERIALS AND METHODS: 30 patients enrolled
      in the study. The respiratory functions of the patients were measured at three
      different stages during angiography (before, immediately after and 2 h later) and
      arterial blood gas analyses were performed at six stages during CA (before,
      immediately after the insertion of angiography catheter, 2 min after the
      injection of contrast agent, at the end of angiography, an hour and 2 h after
      angiography). A single, experienced angiographer performed the angiography
      procedures via radial artery route. Totally six multiple angled views of the left
      and right coronary arteries were recorded in all patients by hand injection. None
      of the patients were performed ventriculography. RESULTS: Angiography caused
      significant reduction in forced expiratory volume in 1 sec [FEV1] (from 103 +/-
      15 to 95 +/- 17, p < 0.01), forced vital capacity [FVC] (from 99 +/- 13 to 95 +/-
      18, p < 0.05) and maximum mid-expiratory flow rate [MMF] (from 95 +/- 33 to 84 +/
      29, p < 0.01) whereas there were no significant changes in the mean FEV1/FVC
      ratios at different stages of angiography. Statistically significant decrease in
      PaO2 (from 91 +/- 10 to 85 +/- 13 mmHg, p < 0.01) and arterial O2 saturation
      (from 97 +/- 1% to 96 +/- 1%, p < 0.01) were also observed. Data in present study
      showed a clinically insignificant but statistically significant restrictive
      impairment in pulmonary functions. CONCLUSIONS: Diagnostic CA using iohexol
      decreases ventilatory functions in a small but significant extent in patients
      without any overt pulmonary disease.

PMID- 15856628
TI  - Normal angiogram in acute coronary syndromes: the underestimated role of
      alternative substrates of myocardial ischemia.
AB  - The study is aimed at evaluating the real incidence of normal coronary arteries
      and the role of alternative substrates of myocardial ischemia in patients with
      acute coronary syndrome (ACS) but with no coronary artery disease (CAD) in a real
      world secondary care public hospital. The medical records of 941 patients
      undergoing coronary arteriography for ACS within 48 h of onset between January
      1st 2000 and November 1st 2003 were critically reviewed. In 70 patients (7.4%, 35
      males, mean age 60 +/- 17.2 years) no CAD was documented. Alternative substrates
      of acute myocardial ischemia included coronary artery anomalies (7 patients,
      10%), coronary spasm (10 patients, 14.3%), spontaneous coronary dissection (2
      patients, 2.8%), paradoxical embolism through a patent foramen ovale (4 patients,
      5.7%), embolism from left atrium or calcified aortic valve (4 patients, 5.7%),
      imbalance between oxygen demand and supply (20 patients, 28.5%), mitral valve
      prolapse (11 patients, 15.7%). No alternative substrates were found in 12
      patients (17.1%). Patients with no CAD are more frequently female and younger.
      Absence of CAD is an uncommon finding in patients undergoing coronary artery
      angiography for ACS.

PMID- 15856629
TI  - Cardiac involvement in non-Hodgkin's lymphoma: with and without HIV infection.
AB  - AIDS has resulted in a significant increase in the incidence of both primary and
      secondary cardiac lymphomas. Prognosis of HIV associate cardiac non-Hodgkin's
      lymphoma is poor with very limited survival. Many cases of cardiac involvement in
      lymphoma remain undetected secondary to non-specific symptoms. Chemotherapy may
      produce remission in some cases. We report two cases of cardiac involvement with
      B-cell lymphoma. The first patient had a history of AIDS while the second had no
      evidence of HIV infection.

PMID- 15856630
TI  - Late infective endocarditis after cholecystectomy in a patient with repaired
      tetralogy of Fallot: a case report.
AB  - Late endocarditis after surgical repair of tetralogy of Fallot is rare. We
      describe a case of endocarditis following cholecystectomy in a 22-year old
      patient with repaired tetralogy of Fallot. After cholecystectomy, the patient was
      referred to a cardiology clinic with unexplained fever and suspicion of
      endocarditis. Echocardiography revealed a large mass at the basal level of
      interventricular septum. Endocarditis was diagnosed on the basis of clinical and
      echocardiographic findings and antibiotic treatment was initiated immediately.
      Nine days later, the clinical status of the patient deteriorated and urgent
      surgery was performed. Patch dehiscence which mimicked a large vegetation, and
      multiple vegetations on the patch were found during operation. The patch was
      removed and ventricular septum defect was repaired with a new dacron patch.
      Enterobacter agglomerans was isolated in the vegetation cultures.

PMID- 15856631
TI  - Combined CT-PET criteria for myocardial viability and scar: a preliminary report.
AB  - Identification of hibernating myocardium and its differentiation from scar tissue
      is an important clinical task for implementing different treatment options. The
      recognition of combined criteria in spiral-CT and PET for hibernating myocardium
      and scar will be important as hybrid CT-PET moves into the main stream of routine
      oncologic and cardiovascular imaging. A review of three cases, initially referred
      for CT evaluation of cardiac or pulmonary conditions with subsequent F-18 FDG
      body PET imaging, was presented for illustration as a combined CT-PET cardiac
      evaluation. The real value of this combined anatomical and functional evaluation
      will be with the upcoming concurrent CT and PET imaging using dedicated multi
      slice CT-PET scanners.

PMID- 15856632
TI  - Cardiac MRI in the isolated porcine heart reveals possible etiology of sudden
      right heart failure following heart transplantation.
AB  - Occurrence of immediate post-transplant heart failure in the cardiac transplant
      recipient is typically attributed to elevated pulmonary vascular resistance,
      however other etiologies may play a role. At the completion of the transplant,
      free air, which has collected in the donor heart, is vented via an aortotomy.
      Free air may rise into the right coronary artery and obstruct reperfusion of the
      right ventricle. Cardiac perfusion MRI may offer a method of non-invasively
      determining the presence of air embolus. The objectives in the pilot study were
      to identify steps in the donor process where free air could enter into the aortic
      root causing obstruction of perfusion of the coronary arteries. A change in
      surgical technique could then be used to eliminate a portal of entry and cardiac
      perfusion MRI could validate the technique. Standard cardiectomy was compared to
      a variation in technique in two animals. Pulmonary vein ligation was completed in
      the experimental model before completion of cardiectomy. Both hearts were
      isolated and imaged using T1-weighted FLASH sequence and gadolinium contrast via
      the aortic root. Cardiac perfusion MRI imaging of the heart with the unligated
      pulmonary vein revealed evidence of air embolus and no perfusion of the right
      coronary artery compared to the ligated heart. Anatomically, the right coronary
      artery is anterior in the mediastinum compared to the left coronary artery. Air
      emboli preferentially rise into the right coronary and can obstruct flow into the
      right heart. Cardiac perfusion MRI offers an effective method to evaluate the
      isolated pre-transplant heart for perfusion defects.

PMID- 15856633
TI  - Quantification of myocardial function using tagged MR and cine MR images.
AB  - Magnetic Resonance Imaging (MRI) is recognized as a relevant modality for
      dynamically imaging the heart anatomy and function, and achieving satisfying
      qualitative diagnosis. Reliable methods for quantitatively analyzing cardiac
      motion from MR images remain, however, to be elaborated. This paper presents a
      novel approach for measuring myocardial deformations from tagged MRI sequences.
      Based on efficient pixel-based statistical non-rigid registration, it allows for
      automatically extracting local/global deformation parameters at the pixel and
      myocardial segment scales. Its performances for assessing the myocardial function
      are illustrated both for the normal heart and for pathologies of the ischemic and
      dilated cardiomyopathic type.

PMID- 15856634
TI  - Routine breath-hold gradient echo MRI-derived right ventricular mass, volumes and
      function: accuracy, reproducibility and coherence study.
AB  - Right ventricular (RV) dysfunction is a predictor of poor outcome in patients
      with heart disease. Conventional imaging modalities fail to assess RV volumes
      accurately. We sought to assess the accuracy and reproducibility of routine
      breath-hold gradient echo magnetic resonance imaging (MRI)-derived RV mass,
      volumes and function. We assessed: (1) The accuracy of in vivo MRI-derived RV
      mass in comparison to the RV weight in 9 minipigs. (2) Intra- and inter-observer
      reproducibility of RV mass, end-diastolic (EDV) and end-systolic (ESV) volumes
      and ejection fraction (EF) in 15 normal volunteers and 10 patients with heart
      disease. (3) Inter-study reproducibility of the former parameters in 25 coronary
      artery disease patients. (4) The correlation between right and left ventricular
      stroke volumes in the total population. Strong statistically significant
      correlations were found between: (1) MRI-derived RV mass and RV weight (r = 0.98,
      bias = 2.5 g), (2) Intra-observer measurements of RV mass (r = 0.96, bias = 0.5
      g), EDV (r = 0.99, bias = -1.5 ml), ESV (r = 0.98, bias = 0.1 ml) and EF (r =
      0.92, bias = -1.4%), (3) Inter-observer measurements of RV mass (r = 0.95, bias =
      1.1 g), EDV (r = 0.98, bias = -1.1 ml), ESV (r = 0.98, bias = 1.2 ml) and EF (r =
      0.87, bias = -1.9%), (4) Inter-study measurements of RV mass (r = 0.91, bias = 
      0.1 g), EDV (r = 0.96, bias = 3.8 ml), ESV (r = 0.98, bias = 0.3 ml) and EF (r =
      0.90, bias = 0.9%), (5) MRI-derived right and left ventricular stroke volumes (r
      = 0.87). The assessment of the RV mass, volumes and function by routine breath
      hold gradient echo MRI is accurate and highly reproducible. The correlation
      between left and RV MRI-derived stroke volumes indicates excellent coherence of
      simultaneous bi-ventricular volume measurements.

PMID- 15856635
TI  - Tropical endomyocardial fibrosis (Davies' disease): case report demonstrating the
      role of magnetic resonance imaging.
AB  - Tropical endomyocardial fibrosis (TEMF), a restrictive cardiomyopathy of unclear
      etiology, is an endemic disease in equatorial Africa, South America and India.
      The patients are usually young, the onset of the disease and its clinical
      manifestations insidious, and the prognosis poor. We currently present a 50-year
      old Congolese female who was referred with symptoms of progressive right-sided
      heart failure due to isolated TEMF of the right ventricle. Surgical resection of
      regional endomyocardial fibrosis was not possible and our patient was referred
      for cardiac transplantation. Cardiac magnetic resonance imaging (CMR)
      demonstrated the primary and secondary structural and functional abnormalities.
      CMR seems ideally suited to diagnose this condition and monitor response to
      medical and/or surgical therapy.

PMID- 15856636
TI  - Metastatic melanoma of the left ventricle: cardiac imaging in the diagnosis and
      surgical approach.
AB  - A mass lesion occupying the left ventricle was noted on a screening CT scan in a
      42-year-old man with a history of malignant melanoma. Subsequent echocardiography
      and cardiac MR imaging provided further hemodynamic and anatomic characterization
      of the lesion. These studies were also essential in guiding the proper surgical
      approach to allow extensive resection of the large mass without disrupting
      cardiac structures and function. The unique clinical aspects of this case are the
      unusual location for a lone cardiac metastasis of melanoma and the asymptomatic
      presentation despite the large size of the tumor and its apparent obstruction of
      ventricular outflow. The clinical and imaging features of this patient's
      threatening cardiac lesion are presented.

PMID- 15856637
TI  - Incidence of stent under-deployment as a cause of in-stent restenosis in long
      stents: take your lesson!

PMID- 15856638
TI  - Three-dimensional imaging for the guidance of coronary interventional procedures:
      impact on clinical decision making?

PMID- 15856639
TI  - Advances in cardiac CT imaging: 64-slice scanner.
AB  - BACKGROUND: Clinical progress by the development of multi-slice CT (MSCT)
      technology beyond 16 slices can more likely be expected from further improved
      spatial and temporal resolution rather than from a mere increase in the volume
      coverage speed. We present an evaluation of a recently introduced 64-slice CT
      (64SCT) system, which makes use of a periodic motion of the focal spot in the
      longitudinal direction (z-flying focal spot) to double the number of
      simultaneously acquired slices. MATERIALS AND METHODS: A recently introduced
      64SCT system (SOMATOM Sensation 64, Siemens Medical Solutions, Forchheim,
      Germany) is being described and tested in first clinical practice, applying the
      following parameters: z-flying focal spot technology, 64 x 0.6 mm slices; spatial
      resolution, 0.4 x 0.4 x 0.4 mm; gantry rotation time, 330 ms; temporal
      resolution, 83-165 ms. Various phantom studies and first clinically implemented
      protocols are being described, to evaluate the full spectrum of possible
      applications for this scanner type, with a focus on cardiac imaging. RESULTS: ECG
      gated cardiac scanning with this 64-slice CT system benefits clearly from both
      the improved temporal resolution and improved spatial resolution. These benefits
      enable a more reliable assessment of mixed plaques, due to reduced partial
      voluming and beam-hardening artefacts caused by calcifications, and holds great
      promise for the reliable assessment of in-stent stenoses, as stent lumen
      visibility is clearly improved as compared to earlier MSCT systems. With the
      increased volume coverage and acquisition speed of the 64SCT system, a
      comprehensive emergency protocol of the thorax becomes feasible within an
      acceptable breath-hold time, performing an ECG-gated CT angiography of the
      complete thoracic vasculature. This protocol enables a detailed assessment of the
      thoracic aorta, the pulmonary arteries and the coronary arteries in one single
      examination. CONCLUSIONS: 64SCT Cardiac imaging provides an increased spatial
      resolution with an isotropic voxel size of 0.4 mm and an improved temporal
      resolution of 83-165 ms. These benefits hold great promise especially for fast
      moving organs requiring detailed imaging, such as the heart and coronary
      arteries.

PMID- 15856640
TI  - Catheter contrast-enhanced coronary CT-angiography using an aortic root injection
      -preliminary technical development in four patients.
AB  - The feasibility of performing coronary computed tomographic angiography (CTA)
      with an intra-aortic injection of iodinated contrast was tested in four patients
      immediately following diagnostic cardiac catheterization and placement of a 6
      french pigtail catheter into the aortic root. A diluted contrast mixture [75 cc
      Omnipaque 350 mixed with 125 cc normal saline (4-slice scanner) vs. 40 cc
      Omnipaque 350 mixed with 60 cc normal saline (16-slice scanner)] was injected at
      a rate of 6 to 7.7 cc/sec at the onset of breath-hold and helical (4 slice, n=3,
      and 16-slice, n=1) retrospective ECG-triggered acquisition. The proximal and
      distal coronary vasculature including small tributaries were depicted with high
      signal-to-noise (S/N) and free from underlying blood pool enhancement. The right
      coronary artery was sub optimally enhanced in two patients. No significant
      disease was found on CTA or XRA in two patients; however, severe multivessel
      disease was demonstrated on both modalities in two patients. Catheter contrast
      enhanced coronary CTA is feasible utilizing low injection rates and low iodinated
      contrast volumes, however, catheter modifications are required for consistent and
      homogeneous opacification of the aortic root.

PMID- 15856641
TI  - Noninvasive coronary angiography: agreement of multi-slice spiral computed
      tomography and selective catheter angiography.
AB  - BACKGROUND: Technology advances in multislice detector computed tomography (MSCT)
      cardiac scanning, specifically in the application of intravenous injected
      contrast coronary angiography with EKG gating have led to the availability of
      this procedure in every day outpatient cardiac medicine. OBJECTIVE: The aim of
      this study is to test the head to head direct coronary angiography with MSCT
      coronary angiography in clinical situations where cardiac cath is traditionally
      utilized for management decisions. METHODS: We limited our analysis to vessels
      felt to be 1.5 mm or greater in diameter, recognizing diagnostic accuracy and
      medical importance of smaller vessels is low. All 50 patients (52% men, 48% women
      age range 34-78) were studied because of the clinical suspicion of obstructive
      coronary atherosclerosis. Blinded experts in direct and in MSCT independently
      read the studies and resolved disparities by a subsequent discussion. Standard
      protocols for direct and for MSCT angiography were used including use of IV and
      oral beta blockade to keep the heart rate at or below 60 beats per minute.
      RESULTS: 392 vessels were evaluated. MSCT provided images of sufficient technical
      quality to permit diagnosis in 98% (49/50) of cases. MSCT was 96% accurate in
      identifying patients as having either no disease, single vessel disease, or
      multiple vessel disease. For all vessels, MSCT identification of stenotic lesions
      of >50% were as follows: sensitivity 87%, specificity 97%, positive predictive
      value 80%, and negative predictive value 98%. Pearson correlation results between
      direct catheter and MSCT for absolute stenotic percentages were left main (0.92 p
      < 0.0001), left anterior descending (0.94 p < 0.0001), circumflex (0.94 p <
      0.0001), first obtuse marginal (0.85 p < 0.0001), and right coronary artery (0.89
      p < 0.0001). CONCLUSION: The accuracy of MSCT angiography compared favorably with
      that of direct cardiac cath in this cohort of patients. The high specificity of
      these findings suggest that one particular use of this technique will be to
      eliminate many unnecessary cardiac catheterization procedures by excluding
      obstructive, and therefore potentially PCI requiring, coronary artery disease.
      The medical cost savings of such an application may be very significant and bears
      further study.

PMID- 15856642
TI  - Imaging of atherosclerotic plaque.
AB  - The behavior and composition of coronary atherosclerotic plaques are ultimately
      responsible for the threat of acute ischemic events in patients with coronary
      artery disease. Different imaging modalities have been developed over the last
      several years in order to better characterize the atherosclerotic plaque and
      attempt to predict those in peril of complication. Since its implementation into
      cardiovascular medicine, nearly 40 years ago, coronary angiography has been the
      mainstay of identifying hemodynamically stenotic lesions. Further investigation
      into imaging modalities have suggested, however, that the degree of stenosis is
      only one of several factors influencing a plaque's tendency to rupture. Recent
      advances in imaging modalities, including invasive and non-invasive studies, have
      allowed us to examine the histological components that comprise these plaques.
      Specific information such as variations in temperature, plaque stiffness and
      calcification level is currently being researched as well as biological and
      chemical markers. The ultimate goal is to visualize the plaque and its
      characteristics, stratify its risk for acute events, be able to apply this
      modality to the general population of cardiac patients, while exposing the
      patient to minimal risk and having adequate positive and negative predictive
      values. This manuscript will review the more recent data concerning these
      interventions and their individual characteristics.

PMID- 15856643
TI  - Development of a lipoprotein based molecular imaging MR contrast agent for the
      noninvasive detection of early atherosclerotic disease.
AB  - INTRODUCTION: Currently there are no clinically available means of noninvasively
      detecting early atherosclerotic disease because these lesions are characterized
      by an accumulation of extracellular lipid and foam cells, but a lack of
      significant wall thickening or architectural distortion. OBJECTIVE: We
      hypothesize that a paramagnetically labeled low density lipoprotein (LDL) could
      serve as a functional probe to detect sites of abnormal lipid metabolism in the
      vessel wall that represent sites of early disease. METHODS: Isolated LDL was
      first incubated with manganese-mesoporphyrin, a hydrophobic MR contrast agent
      (MnMeso). Size exclusion chromatography and absorption mass spectroscopy were
      performed on the resulting samples to prove that an association between the two
      occurred. Subsequently, foam cell cultures (n=7) were incubated (10-30 microg/ml
      for 48 h) with these labeled lipoproteins and the T1 relaxivity of centrifuged
      pellets of these cells was determined by using an inversion recovery sequence on
      a 1.5T scanner. These results were compared to control measurements made from
      foam cell cultures fed unlabeled lipoproteins (n=7). RESULTS: Measured T1
      relaxation times of the cells fed the MnMeso-LDL (443.3 +/- 51.8 ms) was
      significantly different from the T1 relaxivity obtained from cells fed unlabeled
      lipoproteins (661.3 +/- 60.9 ms). These findings indicate that the amount of
      contrast bound to the constructed lipoproteins is sufficient to produce
      measurable MR signal changes noninvasively. CONCLUSIONS: The study results
      support the feasibility of future in vivo MR experiments with labeled
      lipoproteins to assess lipoprotein kinetics in the vessel wall, which will
      hopefully provide a means of detecting early atherosclerotic disease.

PMID- 15856644
TI  - A review of the complementary information available with cardiac magnetic
      resonance imaging and multi-slice computed tomography (CT) during the study of
      congenital heart disease.
AB  - The incidence of congenital heart disease is approximately 4-6 per 1000 new
      births; however, the number of people living with congenital heart disease (CHD)
      is increasing, because of improved diagnosis, medical, and surgical management.
      While echocardiography continues to be the mainstay of non-invasive imaging,
      cardiac MRI (cMRI) and computed tomography (CT) have taken on increasing roles in
      the diagnosis of congenital heart disease in infants, children, and importantly,
      adults who may have limited echocardiographic windows, especially if post
      operative. Cardiac MRI and multi-slice CT can complement the diagnostic
      information obtained by echocardiography and invasive cardiac catheterization.
      Post-operative imaging of CHD is especially enhanced by the spin echo MRI
      techniques, while gradient cine echo MRI imaging allows functional information
      that is not encumbered by geometric assumptions. Phase contrast (velocity
      encoding) cardiac MRI data can provide information about flow, allowing accurate
      determination of regurgitation and shunt volume. Gadolinium enhanced cMRI or
      three-dimensional reconstructed images from multi-slice CT angiography allow
      excellent delineation of vascular structures in complex heart disease. Coronary
      imaging, while possible with both modalities, appears more facile with fast CT
      imaging. This article reviews the literature to provide an assessment of the
      special techniques and considerations needed during the conduct of cardiac
      MRI/MRA and multi-slice CT examinations during the diagnosis of congenital heart
      disease in pediatric and adult patients.

PMID- 15856645
TI  - Perfusion reserve in asymptomatic individuals.

PMID- 15856646
TI  - Whole body MR angiography screening.
AB  - Lack of side effects, diagnostic accuracy and recent improvements in technology
      qualify magnetic resonance imaging for preventive cardiovascular imaging. The
      purpose of this study was to assess the feasibility of a comprehensive contrast
      enhanced three-dimensional whole-body MR (magnetic resonance) angiography
      examination technique using a rolling table platform system with a 1.5-T MR
      system. The examination yielded diagnostic image quality in 5312 out of 5400
      (98.3%) evaluated vascular segments in 180 consecutive patients with peripheral
      vascular disease. Besides the proved peripheral vascular disease, additional
      relevant vascular disease was found in 65 vessel segments in 42 patients: carotid
      artery stenosis (n=21), subclavian artery stenosis (n=5), renal artery stenosis
      (n=27) abdominal aortic aneurysm (n=7), aortic dissection (n=5). In 20 patients
      additional imaging studies confirmed the results of whole-body MRA without false
      positive or false negative findings. The described whole-body MR angiography
      protocol appears well suited for comprehensive evaluation of the arterial system
      beyond the peripheral vasculature.

PMID- 15856648
TI  - RDHs can help the underserved.

PMID- 15856647
TI  - Non-invasive analysis of myoblast transplants in rodent cardiac muscle.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) of magnetically labeled stem cells
      is a non-invasive approach that can provide images with high spatial resolution.
      We evaluated the ability of a commercially available, Food and Drug
      Administration (FDA) approved contrast agent to allow the monitoring of myoblast
      transplants in the rodent heart. METHODS AND RESULTS: Primary rat myoblasts were
      efficiently labeled by incubation with ferumoxide-polycation complexes and
      labeled cells retained their normal capacity to generate mature myotubes. Intra
      cellular iron-oxide accumulation resulted in MRI contrast changes, allowing for
      three-dimensional, non-invasive detection of labeled cells in the rodent
      myocardium. Histological analysis of hearts injected with labeled myoblasts or
      control, non-viable myoblasts revealed that areas of MRI contrast changes
      corresponded to iron contained within engrafted myotubes and scavenger cells up
      to two months post-injection. CONCLUSIONS: The high sensitivity of MR imaging
      will allow for non-invasive studies of cardiac stem cell migration and homing.
      Additional techniques are in development to non-invasively determine stem cell
      engraftment rates, viability and differentiation.

PMID- 15856649
TI  - State board member responds to licensure editorial.

PMID- 15856650
TI  - Don't read this.

PMID- 15856651
TI  - The high, high cost of turnover.

PMID- 15856652
TI  - Claim rejections and documentation.

PMID- 15856655
TI  - The two most-asked questions about MDA insurance.

PMID- 15856654
TI  - Six steps for avoiding conflict in your office.

PMID- 15856656
TI  - Dr Kathy Roth: Our choice for ADA President-Elect. Interview by Mike Maihofer.

PMID- 15856657
TI  - Proposed bylaws changes before the 2005 MDA House of delegates.

PMID- 15856658
TI  - Dr. Ray Stevens: dentist, photographer, fluoridation pioneer.

PMID- 15856659
TI  - Reducing drug usage and adverse effects. Part I: Diabetes management.

PMID- 15856660
TI  - Weight loss through behavior modification. Tips for providing comprehensive
      client education.

PMID- 15856661
TI  - Medication management (MM).

PMID- 15856662
TI  - Sanitarians' work with indoor-tanning businesses: findings from interviews in two
      major metropolitan areas.
AB  - In spite of health risks, indoor tanning is a popular practice and a growing
      industry. Although published studies indicate that tanning businesses' compliance
      with regulations is poor, no studies describe enforcement activity and the
      related knowledge and perceptions of environmental health professionals. As part
      of a larger study of indoor tanning in Minnesota and Massachusetts, both states
      with statutes that regulate tanning, the investigation reported in this paper
      involved interviews of 27 sanitarians in the Twin Cities and 30 sanitarians in
      the Boston metropolitan area about their awareness, experiences, and practices.
      Overall, Massachusetts performed better than Minnesota with respect to
      familiarity with regulations (93 percent versus 67 percent), routine business
      inspections (90 percent of agencies versus 27 percent), and priority given by
      agencies to indoor-tanning work-differences likely attributable to a stronger
      state statute. Participants in both states, however, recalled few aspects of the
      regulations and were able to identify few of the health risks associated with
      indoor tanning, and most reported receiving inadequate training. Various steps
      must be taken to improve environmental health work with tanning businesses,
      including educating the public, strengthening regulations, addressing resource
      issues, and training sanitarians.

PMID- 15856663
TI  - Tattooing, body piercing, and permanent cosmetics: a historical and current view
      of state regulations, with continuing concerns.
AB  - The popularity of tattooing, body piercing, and permanent cosmetics demands up-to
      date state legislation. The objective of this article is to present a historical
      perspective and nationwide review of current state regulations for body art.
      Methods comprised Internet and telephone inquiries to state agencies. It was
      found that while 36 states have changed their body art legislation since 1998,
      the overall strength of the regulations varies widely. The author concludes that
      it is unrealistic, given the amount of body art performed in the United States,
      to prohibit body art, emphasize only business licensing, or have limited state
      regulations while local municipalities establish separate policies. Concerns
      remain about standard precautions, adequate documentation of complications, and
      lack of uniform regulations. Quality protection will mean taking a more
      comprehensive approach to effective regulations and enforcement.

PMID- 15856664
TI  - Efficacy of the Community Reinvestment Act in promoting lead abatement.
AB  - The efficacy of the Community Reinvestment Act (CRA) in assisting homeowners or
      landlords in urban areas of New Jersey to finance lead abatement was evaluated in
      the study reported here, as was the effectiveness of the abatement. The study
      involved working with homeowners, banks, local health departments, and
      communities to facilitate financing for lead abatement, and collecting
      environmental-dust specimens from some of the participants' homes before and
      after abatement. Of the 113 interested subjects, 59 (52 percent) completed
      abatement of their homes. Of the 58 who applied for CRA loans, 21 received
      approvals and had the work completed. Thirty-nine of the homeowners found
      alternate means of financing abatement. The environmental data showed a
      significant decrease on the windowsills in the 4aated homes, but not on the
      floors. In conclusion, one-on-one counseling of homeowners about funding was
      associated with more than 50 percent success in completing abatement, The CRA
      loans' accounted for about one-third of the abated units. The lead abatement was
      effective in removing lead paint from the windows, but not in reducing dust lead
      levels on the floors.

PMID- 15856665
TI  - Mapping of arsenic content and distribution in groundwater in the southeast
      Pampa, Argentina.
AB  - The presence and spatial distribution of groundwater arsenic was evaluated in an
      area of approximately 6000 square kilometers that extends along the southeast
      border of the subhumid pampa plains of southeast Buenos Aires Province,
      Argentina. Groundwater constitutes the only easily exploitable source of water
      for the large rural and suburban population in the area, both for human
      consumption and for use in agricultural and livestock production. In the study
      area, 56.3 percent of water samples had seriously elevated arsenic levels (0.06
      to 0.5 milligrams per liter [mg/L]), constituting a risk for human consumption
      and agricultural and livestock use. In 27.2 percent of the samples, arsenic
      content ranged from just below the World Health Organization-recommended maximum
      level of 0.01 mg/L to 0.05 mg/L. Only in 16.5 percent of the samples did the
      water contain no or very low concentrations. The contamination of domestic water
      supplies in the study area constitutes a serious water quality problem since this
      element has been identified as the cause of a number of health problems,
      including cancer.

PMID- 15856666
TI  - The Safe Drinking Water Act and decentralized/onsite wastewater.

PMID- 15856667
TI  - What's the best way to manage urgent and emergent OR cases?

PMID- 15856668
TI  - Study links disruptive behavior to negative patient outcomes.

PMID- 15856669
TI  - Get with the flow, keynoter to advise.

PMID- 15856670
TI  - CMS consent guideline riles hospitals.

PMID- 15856671
TI  - Dispensing machines and med errors.

PMID- 15856672
TI  - How do we sequence urgent cases?
AB  - Because the medical deadline is determined in hours, there is a precise
      mathematical definition for OR efficiency, and the impact on patient delays can
      be estimated. The priorities described above will give a single answer to a
      sequence of urgent cases.

PMID- 15856673
TI  - A fair policy for bumping OR cases.

PMID- 15856674
TI  - Making disruptive behavior policy real.

PMID- 15856675
TI  - Disruptive behavior: what's the law?

PMID- 15856676
TI  - Lines blurring between OR, imaging.

PMID- 15856677
TI  - Help! I have a problem employee.

PMID- 15856678
TI  - Getting MD, staff buy-in for QI projects.

PMID- 15856679
TI  - Influence of angiogenesis inhibitors, endostatin and PF-4, on lymphangiogenesis.
AB  - This study was designed to screen potential safe and effective inhibitors of
      lymphangiogenesis. Lymphatic endothelial cells from pig thoracic duct were
      isolated and cultured. The control group, 3 endostatin, and 3 PF-4 experimental
      groups were tested for effects on proliferation and distance of migration of the
      cultured cells by two methods (method of the scraping line and MTT assay), and
      observations by light, confocal, and electron microscopy were also made. Total
      cells migrating past the scrape line for the endostatin control group was 28.6 +/
      1.2 (mean +/- standard error) and the 3 endostatin experimental groups (50
      ng/ml, 100 ng/ml, and 150 ng/ml), respectively, were 17.5 +/- 0.6, 10.5 +/- 0.5,
      and 4.8 +/- 0.3 (all p < 0.05 cf control). Migration distance for the endostatin
      control group was 381.7 +/- 9.67 microm, and the migration distance of the 3
      endostatin experimental groups, respectively, were 252.9 +/- 5.58, 164.5 +/-
      7.09, and 91.2 +/- 7.98 microm (all p < 0.05). Cell migration number for the PF-4
      control group was 28.3 +/- 1.0 compared with doses of 40 ng/ml, 80 ng/ml, or 120
      ng/ml of PF-4, respectively, were 13.6 +/- 0.7, 9.5 +/- 0.6, and 4.6 +/- 0.4 (all
      p < 0.05 cf control). Migration distance of cells in PF-4 control group was 419.9
      +/- 5.87 microm, and the 3 PF-4 experimental groups, respectively, were 199.2 +/-
      8.16, 152.5 +/- 7.28, and 104.2 +/- 6.70 microm (all p < 0.05 cf control). The
      MTT assay confirmed that as the concentrations of endostatin and PF-4 were
      increased, the inhibitory effect was increased. We conclude that endostatin and
      PF-4 are able to inhibit the migration and proliferation of lymphatic endothelial
      cells, and these effects are dose-dependent.

PMID- 15856680
TI  - Diagnostic protocol for lymphoscintigraphy in newborns.
AB  - The purpose of this methods paper is to offer pediatricians and nuclear medicine
      physicians a diagnostic protocol for performing lymphoscintigraphy in newborns
      that may be useful for enhancing diagnosis and management of newborns with
      congenital lymphatic abnormalities. Indications for lymphoscintigraphy, choice of
      tracer, optimal dose, routes of administration, methods of data acquisition,
      timing, and interpretation of results for newborns are presented and discussed.

PMID- 15856681
TI  - Unusual lymphatic drainage pattern in a patient with lymphedema of lower
      extremities.

PMID- 15856682
TI  - Pacinian corpuscle in human lymph node.

PMID- 15856683
TI  - Foot volume estimates based on a geometric algorithm in comparison to water
      displacement.
AB  - Assessing lower extremity limb volume and its change during and after lymphedema
      therapy is important for determining treatment efficacy and documenting outcomes.
      Although leg volumes may be determined by tape measure and other methods, there
      is no metric method to routinely assess foot volumes. Exclusion of foot volumes
      can under- or overestimate therapeutic progress. Our aim was to develop and test
      a metric measurement procedure and algorithm for practicing therapists to use to
      estimate foot volumes. The method uses a caliper and ruler to measure foot
      dimensions at standardized locations and calculates foot volume (VM) by a
      mathematical algorithm. VM was compared to volumes measured by water displacement
      (Vw) in 30 subjects (60 feet) using regression analysis and limits of agreement
      (LOA). Vw and VM (mean +/- sd) were similar 857 +/- 150 ml vs. 859 +/- 154 ml,
      and were highly correlated VM = 1.00Vw + 1.67 ml, r = 0.965, p < 0.001. The LOA
      for absolute volume differences and percentages were respectively +/- 79.6 ml and
      +/- 9.28 %. These results indicate that this metric method can be a useful
      alternative to water displacement when foot volumes are needed, but the water
      displacement method is contraindicated, impractical to implement, too time
      consuming or is not available.

PMID- 15856684
TI  - Contemporary issues in management of chronic lymphedema: personal reflection on
      an experience with 1065 patients.

PMID- 15856685
TI  - The evolution of circulation, homeostasis and immunity: an historical account
      from a lymphologist/hematologist viewpoint.

PMID- 15856686
TI  - The history of lymphology.

PMID- 15856687
TI  - Group health uses capitation to expand access and quality.

PMID- 15856688
TI  - Keystone Mercy expands capitation payments to PCPs.
AB  - Keystone Mercy Health Plan, Philadelphia, enhances its capitation contracting
      strategy by providing financial incentives for capitated primary care physicians
      to provide high-quality services.

PMID- 15856689
TI  - Survey: consumers willing to accept managed care restrictions.
AB  - Data Insight: Health care consumers are willing to accept tight managed care
      networks again if health plans and physicians maintain high quality, according to
      a newly published survey.

PMID- 15856690
TI  - Chiropractic capitation remains strong as evidence of cost savings mounts.
AB  - Capitation remains a fundamental strategy of health plans in offering
      complementary and alternative medicine services to members.

PMID- 15856691
TI  - Evolution of antibiotic resistance by human and bacterial niche construction.
AB  - Antibiotic treatment by humans generates strong viability selection for
      antibiotic-resistant bacterial strains. The frequency of host antibiotic use
      often determines the strength of this selection, and changing patterns of
      antibiotic use can generate many types of behaviors in the population dynamics of
      resistant and sensitive bacterial populations. In this paper, we present a simple
      model of hosts dimorphic for their tendency to use/avoid antibiotics and
      bacterial pathogens dimorphic in their resistance/sensitivity to antibiotic
      treatment. When a constant fraction of hosts uses antibiotics, the two bacterial
      strain populations can coexist unless host use-frequency is above a critical
      value; this critical value is derived as the ratio of the fitness cost of
      resistance to the fitness cost of undergoing treatment. When strain frequencies
      can affect host behavior, the dynamics may be analyzed in the light of niche
      construction. We consider three models underlying changing host behavior:
      conformism, the avoidance of long infections, and adherence to the advice of
      public health officials. In the latter two, we find that the pathogen can have
      quite a strong effect on host behavior. In particular, if antibiotic use is
      discouraged when resistance levels are high, we observe a classic niche
      construction phenomenon of maintaining strain polymorphism even in parameter
      regions where it would not be expected.

PMID- 15856692
TI  - The evolution of sperm-allocation strategies and the degree of sperm competition.
AB  - The prevailing viewpoint in the study of sperm competition is that male sperm
      allocation strategies evolve in response to the degree of sperm competition an
      ejaculate can expect to experience within a given mating. If males cannot assess
      the degree of sperm competition their ejaculate will face and/or they are unable
      to facultatively adjust sperm investment in response to perceived levels of
      competition, high sperm allocation (per mating) is predicted to evolve in the
      context of high sperm competition. An implicit assumption of the framework used
      to derive this result is that the degree of sperm competition is unaffected by
      changes in sperm-allocation strategies. We present theory based on an alternative
      perspective, in which the degree of sperm competition and the sperm-allocation
      strategy are coupled traits that coevolve together. Our rationale is that the
      pattern of sperm allocation in the population will, in part, determine the level
      of sperm competition by affecting the number of ejaculates per female in the
      population. In this setting, evolution in sperm-allocation strategies is driven
      by changes in underlying environmental parameters that influence both the degree
      of sperm competition and sperm allocation. This change in perspective leads to
      predictions that are qualitatively different from those of previous theory.

PMID- 15856693
TI  - The analysis of reaction norms for age and size at maturity using maturation rate
      models.
AB  - Reaction norms for age and size at maturity are being analyzed to answer
      important questions about the evolution of life histories. A new statistical
      method is developed in the framework of time-to-event data analysis, which
      circumvents shortcomings in currently available approaches. The method emphasizes
      the estimation of age- and size-dependent maturation rates. Individual
      probabilities of maturation during any given time interval follow by integrating
      maturation rate along the growth curve. The integration may be performed in
      different ways, over ages or sizes or both, corresponding to different
      assumptions on how individuals store the operational history of the maturation
      process. Data analysis amounts to fitting generalized nonlinear regression models
      to a maturation status variable. This technique has three main advantages over
      existing methods: (1) treating maturation as a stochastic process enables one to
      specify a rate of maturation; (2) age and size at which maturation occurs do not
      have to be observed exactly, and bias arising from approximations and
      interpolations is avoided; (3) ages at which sizes are measured and maturation
      status are observed can differ between individuals. An application to data on the
      springtail Folsomia candida is presented. Models with age-dependent integration
      of maturation rates were preferred. The analysis demonstrates a significant size
      dependence of the maturation rate but no age dependence.

PMID- 15856694
TI  - Evolution of specialization and ecological character displacement of herbivores
      along a gradient of plant quality.
AB  - We study the combined evolutionary dynamics of herbivore specialization and
      ecological character displacement, taking into account foraging behavior of the
      herbivores, and a quality gradient of plant types. Herbivores can adapt by
      changing two adaptive traits: their level of specialization in feeding efficiency
      and their point of maximum feeding efficiency along the plant gradient. The
      number of herbivore phenotypes, their levels of specialization, and the amount of
      character displacement among them are the result of the evolutionary dynamics,
      which is driven by the underlying population dynamics, which in turn is driven by
      the underlying foraging behavior. Our analysis demonstrates broad conditions for
      the diversification of a herbivore population into many specialized phenotypes,
      for basically any foraging behavior focusing use on highest gains while also
      including errors. Our model predicts two characteristic phases in the adaptation
      of herbivore phenotypes: a fast character-displacement phase and a slow
      coevolutionary niche-shift phase. This two-phase pattern is expected to be of
      wide relevance in various consumer-resource systems. Bringing together ecological
      character displacement and the evolution of specialization in a single model, our
      study suggests that the foraging behavior of herbivorous arthropods is a key
      factor promoting specialist radiation.

PMID- 15856695
TI  - Experimental studies of adaptation in Clarkia xantiana. II. Fitness variation
      across a subspecies border.
AB  - Because the range boundary is the locale beyond which a taxon fails to persist,
      it provides a unique opportunity for studying the limits on adaptive evolution.
      Adaptive constraints on range expansion are perplexing in view of widespread
      ecotypic differentiation by habitat and region within a species' range (regional
      adaptation) and rapid evolutionary response to novel environments. In this study
      of two parapatric subspecies, Clarkia xantiana ssp. xantiana and C. x. ssp.
      parviflora, we compared the fitness of population transplants within their native
      region, in a non-native region within the native range, and in the non-native
      range to assess whether range expansion might be limited by a greater intensity
      of selection on colonists of a new range versus a new region within the range.
      The combined range of the two subspecies spans a west-to-east gradient of
      declining precipitation in the Sierra Nevada of California, with ssp. xantiana in
      the west being replaced by ssp. parviflora in the east. Both subspecies had
      significantly higher fitness in the native range (range adaptation), whereas
      regional adaptation was weak and was found only in the predominantly outcrossing
      ssp. xantiana but was absent in the inbreeding ssp. parvifilora. Because
      selection intensity on transplants was much stronger in the non-native range
      relative to non-native regions, there is a larger adaptive barrier to range
      versus regional expansion. Three of five sequential fitness components accounted
      for regional and range adaptation, but only one of them, survivorship from
      germination to flowering, contributed to both. Flower number contributed to
      regional adaptation in ssp. xantiana and fruit set (number of fruits per flower)
      to range adaptation. Differential survivorship of the two taxa or regional
      populations of ssp. xantiana in non-native environments was attributable, in
      part, to biotic interactions, including competition, herbivory, and pollination.
      For example, low fruit set in ssp. xantiana in the east was likely due to the
      absence of its principal specialist bee pollinators in ssp. parviflora's range.
      Thus, convergence on self-fertilization may be necessary for ssp. xantiana to
      invade ssp. parviflora's range, but the evolution of outcrossing would not be
      required for ssp. parviflora to invade ssp. xantiana's range.

PMID- 15856696
TI  - Colonization, dispersal, and hybridization influence phylogeography of North
      Atlantic sea urchins (Strongylocentrotus droebachiensis).
AB  - We used frequency-based and coalescent-based phylogeographic analysis of sea
      urchin (Strongylocentrotus droebachiensis) mitochondrial DNA (mtDNA) sequences
      and previously published microsatellite data to understand the relative influence
      of colonization and gene flow from older (north Pacific) and younger (northeast
      Atlantic) sea urchin populations on genetic variation in the northwest Atlantic.
      We found strong evidence of survival of northwestern Atlantic populations in
      local Pleistocene glacial refugia: most haplotypes were the same as or closely
      related to Pacific haplotypes, with deep gene genealogies that reflect divergence
      times within the northwestern Atlantic that are much older than the last glacial
      maximum. We detected gene flow across the North Atlantic in the form of
      haplotypes shared with or recently descended from European populations. We also
      found evidence of significant introgression of haplotypes from a closely related
      species (S. pallidus). The relative magnitude of gene flow estimated by
      coalescent methods (and the effective population size differences among oceanic
      regions) depended on the genetic marker used. In general, we found very small
      effective population size in the northeastern Atlantic and high trans-Arctic gene
      flow between the Pacific and northwestern Atlantic. Both analyses suggested
      significant back-migration to the Pacific. However, microsatellites more strongly
      reflected older Pacific migration (with similar effective population sizes across
      the Arctic), whereas mtDNA sequences appeared to be more sensitive to recent
      trans- Atlantic dispersal (with larger differences in effective population size).
      These differences across marker types might have several biological or
      methodological causes, and they suggest caution in interpretation of the results
      from a single locus or class of markers.

PMID- 15856697
TI  - Intraspecific competition and the evolution of virulence in a parasitic
      trematode.
AB  - Intrahost competition between parasite genotypes has been predicted to be an
      important force shaping parasite ecology and evolution and has been extensively
      cited as a mechanism for the evolution of increased parasite virulence. However,
      empirical evidence demonstrating the existence and nature of intraspecific
      competition is lacking for many parasites. Here, we compared within-host
      competitiveness between genetic strains of Schistosoma mansoni with high (HIGH-V)
      or low (LOW-V) virulence to their intermediate snail host, Biomphalaria glabrata.
      Groups of snails were exposed to either one or the other of two parasite strains,
      or a mixed infection of both strains, and the resulting progeny were identified
      using a molecular marker. In two separate experiments investigating simultaneous
      and sequential infections, we demonstrated that the lifetime reproductive success
      of parasite strain HIGH-V was reduced in the presence of a faster replicating
      parasite genotype, LOW-V, regardless of whether it was in a majority or minority
      in the initial inoculum of the simultaneous exposure or of its relative position
      in the sequential exposure experiment. Thus, we demonstrate competition between
      parasite genotypes and asymmetry in competitive success between parasite strains.
      Moreover, since the less virulent strain investigated here had a competitive
      advantage, we suggest that a high frequency of multiple infections could favor
      the evolution of less, rather than more, virulent parasites in this system.

PMID- 15856698
TI  - An intraspecific comparative analysis of character divergence between sympatric
      species.
AB  - Although sympatric character divergence between closely related species has been
      described in a wide variety of taxa, the evolutionary processes responsible for
      generating these patterns are difficult to identify. One hypothesis that can
      explain sympatric differences is ecological character displacement: the sympatric
      origin of morphologically divergent phenotypes in response to selection caused by
      interspecific competition. Alternatively, populations may adapt to different
      conditions in allopatry, with sympatric distributions evolving through selective
      colonization and proliferation of ecologically compatible phenotypes. In this
      study, I characterize geographic variation within two sibling species of rocky
      shore gastropods that have partially overlapping distributions in central
      California. In sympatry, both Nucella emarginata and N. ostrina show significant
      differences in shell shape and shell ornamentation that together suggest that
      where the two species co-exist, divergent phenotypes arose as an evolutionary
      consequence of competition. To examine the evolutionary origins of divergent
      characters in sympatry, I used a comparative method based on spatial
      autocorrelation to remove the portion of the phenotypic variance among
      populations that is explained by genetic distance (using mitochondrial DNA
      sequences and allozyme frequency data). Because the remaining portion of the
      phenotypic variance represents the independent divergence of individual
      populations, a significant sympatric difference in the corrected dataset provides
      evidence of true character displacement: significant sympatric character
      evolution that is independent of population history. After removal of genetic
      distance effects in Nucella, shell shape differences remain statistically
      significant in N. emarginata, providing evidence of significant sympatric
      character divergence. However, for external shell ornamentation in both species
      and shell shape in N. ostrina, the significance of sympatric differences is lost
      in the corrected dataset, indicating that colonization events and gene flow have
      played important roles in the evolutionary history of character divergence in
      sympatry. Although the absence of a widely dispersing planktonic larva in the
      life cycle of Nucella will promote local adaptation, the results here indicate
      that once advantageous traits arise, demographic processes, such as recurrent
      gene flow between established populations and extinction and recolonization, are
      important factors contributing to the geographic pattern of sympatric character
      divergence.

PMID- 15856699
TI  - Conserved ontogeny and allometric scaling of resource acquisition and allocation
      in the Daphniidae.
AB  - Life histories vary widely among taxa, but within phylogenetic groups there may
      be a fundamental framework around which trait variation is organized, perhaps as
      a consequence of lineage-specific developmental constraints. In organisms with
      indeterminate growth, there is an ongoing problem of optimally allocating
      resources between growth and reproduction, and that allocation decision may
      manifest itself through allometric scaling. Previous work on freshwater
      zooplankton has shown that the ontogenetic pattern of resource allocation can be
      described by simple mathematical functions. An important component of
      understanding how such functions can explain life-history variation is to
      discover which parameters in these functions are robust, with respect to both
      resource availability and evolutionary diversification, and which parameters
      exhibit interspecific allometry. To shed light on these issues, detailed life
      table experiments were conducted on eight species in the family Daphniidae
      (Crustacea) at high and low levels of resources. Using data on growth,
      reproduction, and instar duration, the ontogeny of resource allocation to growth
      and reproduction could be described as functions that plateau at or shortly after
      the onset of maturity. To be sure that the results were not an artifact of
      phylogenetic structure, the parameters were tested in a phylogenetically
      controlled fashion. The results suggest a simple set of resource allocation rules
      for daphniids, whereby all species exhibit a similar form of ontogenetic change
      in allocation, and reach a plateau where approximately 94% of available resources
      are allocated to reproduction. The asymptotically maximal rate of net resources
      incorporated in growth and reproduction was positively related to size at
      maturity, whereas the rates of approach to plateaus (for both net resource
      assimilation and proportional allocation to reproduction) were negatively related
      to body size. Per-offspring investment was positively related to the square root
      of size at maturity. Using this approach, a wide range of interspecific variation
      in life-history features can be related to a single underlying trait, the size at
      first reproductive investment.

PMID- 15856700
TI  - Environmental origins of sexually selected variation and a critique of the
      fluctuating asymmetry-sexual selection hypothesis.
AB  - Identifying sources of phenotypic variability in secondary sexual traits is
      critical for understanding their signaling properties, role in sexual selection,
      and for predicting their evolutionary dynamics. The present study tests for the
      effects of genotype, developmental temperature, and their interaction, on size
      and fluctuating asymmetry of the male sex comb, a secondary sexual character, in
      Drosophila bipectinata Duda. Both the size and symmetry of elements of the sex
      comb have been shown previously to be under sexual selection in a natural
      population in northeastern Australia. Two independent reciprocal crosses were
      conducted at 25 degrees and 29 degrees C between genetic lines extracted from
      this population that differed in the size of the first (TC1) and third (TC3) comb
      segments. These temperatures are within the documented range experienced by the
      species in nature. Additive and dominance genetic effects were detected for TC1,
      whereas additive genetic, and Y-chromosomal effects were detected for TC3. TC2
      and TC3 decreased sharply with increasing temperature, by 10% and 22%,
      respectively. In contrast, positional fluctuating asymmetry (PFA) significantly
      increased with temperature, by up to 38%. The results (1) document an important
      source of environmental variance in a sexual ornament expected to reduce trait
      heritability in field populations, and thus act to attenuate response to sexual
      selection, (2) suggest that variation in ornament size reflects differences in
      male condition; and (3) support the general hypothesis that asymmetry in a sexual
      ornament is indicative of developmental instability arising from environmental
      stress. The "environmental heterogeneity" (EH) hypothesis is proposed, and
      supportive evidence for it presented, to explain negative size-FA correlations in
      natural populations. Data and theory challenge the use of negative size-FA
      correlations observed in nature to support the FA-sexual selection hypothesis,
      which posits that such correlations are driven by differences in genetic quality
      among individuals.

PMID- 15856701
TI  - Diversification of the forest beetle genus Tarphius on the Canary Islands, and
      the evolutionary origins of island endemics.
AB  - The flightless beetle genus Tarphius Erichson (Coleoptera: Colydiidae) is a
      distinctive element of the beetle fauna of the Canary Islands with 29 species
      distributed across the five western islands. The majority of Tarphius species are
      rare and intimately associated with the monteverde forest and only two species
      occur on more than one island. In this study we investigate the phylogeography of
      the Canary Island Tarphius, and their relationship to Tarphius from the more
      northerly archipelagos of Madeira and the Azores using maximum parsimony and
      Bayesian inference analysis of mitochondrial cytochrome oxidase I and II sequence
      data. We use geological datings for the Canary Islands, Azores, and Madeira to
      calibrate specific nodes of the tree for the estimation of divergence times using
      a penalized likelihood method. Data suggest that the Canary Island species
      assemblage is of some antiquity, however, much of this species diversity is
      relatively recent in origin. The phylogenetic relationships of species inhabiting
      the younger islands of El Hierro and La Palma indicate that colonization events
      between islands have probably been a significant factor in the evolutionary
      history of the Canary Island species assemblage. A comparison of molecular
      phylogenetic studies of arthropods on the Canary Islands suggests that, in the
      evolution of the arthropod species community of an island, the origin of endemic
      species is initially the result of colonizing lineages differentiating from their
      source populations. However, as an island matures a greater proportion of endemic
      species originate from intra-island speciation.

PMID- 15856702
TI  - Historical demography, selection, and coalescence of mitochondrial and nuclear
      (genes in Prochilodus species of northern South America.
AB  - Fishes of the genus Prochilodus are ecologically and commercially important,
      ubiquitous constituents of large river biota in South America. Recent ecologic
      and demographic studies indicate that these fishes exist in large, stable
      populations with adult census numbers exceeding one million individuals.
      Abundance data present a stark contrast to very low levels of genetic diversity
      (theta) and small effective population sizes (Ne) observed in a mitochondrial
      (mt) DNA dataset obtained for two species, Prochilodus mariae, and its putative
      sister taxon, Prochilodus rubrotaeniatus. Both species occupy major river
      drainages (Orinoco, Essequibo, and Negro) of northeastern South America.
      Disparity between expectations based on current abundance and life history
      information and observed genetic data in these lineages could result from
      historical demographic bottlenecks, or alternatively, natural selection (i.e., a
      mtDNA selective sweep). To ascertain underlying processes that affect mtDNA
      diversity in these species we compared theta and Ne estimates obtained from two,
      unlinked nuclear loci (calmodulin intron-4 and elongation factor-1alpha intron-6)
      using an approach based on coalescent theory. Genetic diversity and Ne estimated
      from mtDNA and nuclear sequences were uniformly low in P. rubrotaeniatus from the
      Rio Negro, suggesting that this population has encountered a historical
      bottleneck. For all P. mariae populations, theta and Ne based on nuclear
      sequences were comparable to expectations based on current adult census numbers
      and were significantly greater than mtDNA estimates, suggesting that a selective
      mtDNA sweep has occurred in this species. Comparative genetic analysis indicates
      that a suite of evolutionary processes involving historical demography and
      natural selection have influenced patterns of genetic variation and speciation in
      this important Neotropical fish group.

PMID- 15856703
TI  - Adaptive migratory divergence among sympatric brook charr populations.
AB  - Ecological processes clearly contribute to population divergence, yet how they
      interact over complex life cycles remains poorly understood. Notably, the
      evolutionary consequences of migration between breeding and non-breeding areas
      have received limited attention. We provide evidence for a negative association
      between interpopulation differences in migration (between breeding and feeding
      areas, as well as within each) and the amount of gene flow (m) among three brook
      charr (Salvelinus fontinalis) populations inhabiting Mistassini Lake, Quebec,
      Canada. Individuals (n = 1166) captured throughout lake feeding areas over two
      consecutive sampling years were genotyped (10 microsatellites) and assigned to
      one of the three populations. Interpopulation differences in migration were
      compared based on spatial distribution overlap, habitat selection, migration
      distance within feeding areas, and morphology. We observed a temporally stable,
      heterogeneous spatial distribution within feeding areas among populations, with
      the extent of spatial segregation related to differential habitat selection
      (represented by littoral zone substrate). Spatial segregation was lowest and gene
      flow highest (m = 0.015) between two populations breeding in separate lake
      inflows. Segregation was highest and gene flow was lowest (mean m = 0.007)
      between inflow populations and a third population breeding in the outflow.
      Compared to outflow migrants, inflow migrants showed longer migration distances
      within feeding areas (64-70 km vs. 22 km). After entering natal rivers to breed,
      inflow migrants also migrated longer distances (35-75 km) and at greater
      elevations (50-150 m) to breeding areas than outflow migrants (0-15 km; -10-0 m).
      Accordingly, inflow migrants were more streamlined with longer caudal regions,
      traits known to improve swimming efficiency. There was no association between the
      geographic distance separating population pairs and the amount of gene flow they
      exchanged. Collectively, our results are consistent with the hypothesis that
      reduced gene flow between these brook charr populations results from divergent
      natural selection leading to interpopulation differences in migration. They also
      illustrate how phenotypic and genetic differentiation may arise over complex
      migratory life cycles.

PMID- 15856704
TI  - Dispersal, philopatry, and infidelity: dissecting local genetic structure in
      superb fairy-wrens (Malurus cyaneus).
AB  - Dispersal influences evolution, demography, and social characteristics but is
      generally difficult to study. Here we combine long-term demographic data from an
      intensively studied population of superb fairy-wrens (Malurus cyaneus) and
      multivariate spatial autocorrelation analyses of microsatellite genotypes to
      describe dispersal behavior in this species. The demographic data revealed: (1)
      sex-biased dispersal: almost all individuals that dispersed into the study area
      over an eight-year period were female (93%; n = 153); (2) high rates of
      extragroup infidelity (66% of offspring), which also facilitated local gene
      dispersal; and (3) skewed lifetime reproductive success in both males and
      females. These data led to three expectations concerning the patterns of fine
      scale genetic structure: (1) little or no spatial genetic autocorrelation among
      females, (2) positive spatial genetic autocorrelation among males, and (3) a
      heterogeneous genetic landscape. Global autocorrelation analysis of the genotypes
      present in the study population confirmed the first two expectations. A novel two
      dimensional local autocorrelation analysis confirmed the third and provided new
      insight into the patterns of genetic structure across the two-dimensional
      landscape. We highlight the potential of autocorrelation analysis to infer
      evolutionary processes but also emphasize that genetic patterns in space cannot
      be fully understood without an appropriate and intensive sampling regime and
      detailed knowledge of the individuals genotyped.

PMID- 15856705
TI  - Blue and green egg-color intensity is associated with parental effort and mating
      system in passerines: support for the sexual selection hypothesis.
AB  - Among several adaptive explanations proposed to account for variation in avian
      egg color, that related to sexual selection is of particular interest because of
      its possible generality. Briefly, it proposes that because biliverdin (the
      pigment responsible for blue-green eggshell coloration) is an antioxidant,
      deposition in the eggshell by laying females may signal the capacity of females
      to control free radicals, despite the handicap of removing this antioxidant from
      their body. If males adjust parental effort in response to the intensity of the
      blue coloration of eggs, thereby investing more in the offspring of high-quality
      mates, blue eggs may represent a postmating sexually selected signal in females.
      Here, by image and spectrophotometric analyses of the eggs of European
      passerines, we tested two different predictions of the hypothesis. First,
      variables related to intraspecific variation in parental effort (i.e., the
      duration of the nestling period controlled for body mass) should be positively
      related to the intensity of blue-green color of the eggshell across species.
      Second, there should be a positive relationship between intensity of blue-green
      color of eggs and degree of polygyny. These predictions were supported: intensity
      of blue-green coloration (i.e., chroma) was significantly related to the duration
      of the nestling period and to degree of polygyny after controlling for possible
      confounding variables (i.e., body mass, incubation period, and nest type) and
      similarity due to common descent. Nest type (hole or nonhole) also explained a
      significant proportion of variation in egg chroma, perhaps reflecting different
      selection pressures (i.e., light conditions, risk of parasitism) affecting
      species with the two types of nests.

PMID- 15856706
TI  - Paternal genetic effects on offspring fitness are context dependent within the
      extrapair mating system of a socially monogamous passerine.
AB  - Avian extrapair mating systems provide an interesting model to assess the role of
      genetic benefits in the evolution of female multiple mating behavior, as
      potentially confounding nongenetic benefits of extrapair mate choice are seen to
      be of minor importance. Genetic benefit models of extrapair mating behavior
      predict that females engage in extrapair copulations with males of higher genetic
      quality compared to their social mates, thereby improving offspring reproductive
      value. The most straightforward test of such good genes models of extrapair
      mating implies pairwise comparisons of maternal half-siblings raised in the same
      environment, which permits direct assessment of paternal genetic effects on
      offspring traits. But genetic benefits of mate choice may be difficult to detect.
      Furthermore, the extent of genetic benefits (in terms of increased offspring
      viability or fecundity) may depend on the environmental context such that the
      proposed differences between extrapair offspring (EPO) and within-pair offspring
      (WPO) only appear under comparatively poor environmental conditions. We tested
      the hypothesis that genetic benefits of female extrapair mate choice are context
      dependent by analyzing offspring fitness-related traits in the coal tit (Parus
      ater) in relation to seasonal variation in environmental conditions. Paternal
      genetic effects on offspring fitness were context dependent, as shown by a
      significant interaction effect of differential paternal genetic contribution and
      offspring hatching date. EPO showed a higher local recruitment probability than
      their maternal half-siblings if born comparatively late in the season (i.e., when
      overall performance had significantly declined), while WPO performed better early
      in the season. The same general pattern of context dependence was evident when
      using the number of grandchildren born to a cuckolding female via her female WPO
      or EPO progeny as the respective fitness measure. However, we were unable to
      demonstrate that cuckolding females obtained a general genetic fitness benefit
      from extrapair fertilizations in terms of offspring viability or fecundity. Thus,
      another type of benefit could be responsible for maintaining female extrapair
      mating preferences in the study population. Our results suggest that more than a
      single selective pressure may have shaped the evolution of female extrapair
      mating behavior in socially monogamous passerines.

PMID- 15856707
TI  - Correlational selection leads to genetic integration of body size and an
      attractive plumage trait in dark-eyed juncos.
AB  - When a trait's effect on fitness depends on its interaction with other traits,
      the resultant selection is correlational and may lead to the integration of
      functionally related traits. In relation to sexual selection, when an ornamental
      trait interacts with phenotypic quality to determine mating success,
      correlational sexual selection should generate genetic correlations between the
      ornament and quality, leading to the evolution of honest signals. Despite its
      potential importance in the evolution of signal honesty, correlational sexual
      selection has rarely been measured in natural populations. In the dark-eyed junco
      (Junco hyemalis), males with experimentally elevated values of a plumage trait
      (whiteness in the tail or "tail white") are more attractive to females and
      dominant in aggressive encounters over resources. We used restricted maximum
      likelihood analysis of a long-term dataset to measure the heritability of tail
      white and two components of body size (wing length and tail length), as well as
      genetic correlations between pairs of these traits. We then used multiple
      regression to assess directional, quadratic, and correlational selection as they
      acted on tail white and body size via four components of lifetime fitness
      (juvenile and adult survival, mating success, and fecundity). We found a positive
      genetic correlation between tail white and body size (as measured by wing
      length), which indicates past correlational selection. Correlational selection,
      which was largely due to sexual selection on males, was also found to be
      currently acting on the same pair of traits. Larger males with whiter tails sired
      young with more females, most likely due to a combination of female choice, which
      favors males with whiter tails, and male-male competition, which favors both tail
      white and larger body size. To our knowledge, this is the first study to show
      both genetic correlations between sexually selected traits and currently acting
      correlational sexual selection, and we suggest that correlational sexual
      selection frequently may be an important mechanism for maintaining the honesty of
      sexual signals.

PMID- 15856708
TI  - Genetic correlations between basal and maximum metabolic rates in a wild rodent:
      consequences for evolution of endothermy.
AB  - According to the aerobic capacity model, endothermy in birds and mammals evolved
      as a correlated response to selection for an ability of sustained locomotor
      activity, rather than in a response to direct selection for thermoregulatory
      capabilities. A key assumption of the model is that aerobic capacity is
      functionally linked to basal metabolic rate (BMR). The assumption has been tested
      in several studies at the level of phenotypic variation among individuals or
      species, but none has provided a clear answer whether the traits are genetically
      correlated. Here we present results of a genetic analysis based on measurements
      of the basal and the maximum swim- and cold-induced oxygen consumption in about
      1000 bank voles from six generations of a laboratory colony, reared from animals
      captured in the field. Narrow sense heritability (h2) was about 0.5 for body
      mass, about 0.4 for mass-independent basal and maximum metabolic rates, and about
      0.3 for factorial aerobic scopes. Dominance genetic and common environmental (=
      maternal) effects were not significant. Additive genetic correlation between BMR
      and the swim-induced aerobic capacity was high and positive, whereas correlation
      resulting from specific-environmental effects was negative. However, BMR was not
      genetically correlated with the cold-induced aerobic capacity. The results are
      consistent with the aerobic capacity model of the evolution of endothermy in
      birds and mammals.

PMID- 15856709
TI  - Experimentally enforced monogamy: inadvertent selection, inbreeding, or evidence
      for sexually antagonistic coevolution?
AB  - There has been recent criticism of experiments that applied enforced monogamous
      mating to species with a long history of promiscuity. These experiments indicated
      that the newly introduced monogamy reversed sexually antagonistic coevolution and
      caused males to evolve to be less harmful to their mates and females to evolve
      reduced resistance to harm from males. Several authors have proposed alternative
      interpretations of these experimental results based on qualitative analysis. If
      well-founded, these criticisms would invalidate an important part of the
      empirical foundation for sexually antagonistic coevolution between the sexes.
      Although these criticisms have a reasonable basis in principle, we find that
      after quantitative evaluation that they are not supported.

PMID- 15856710
TI  - Genetic architecture sets limits on transgressive segregation in hybrid cichlid
      fishes.
AB  - The role of hybridization in the evolution of animal species is poorly
      understood. Transgressive segregation is a mechanism through which hybridization
      can generate diversity and ultimately lead to speciation. In this report we
      investigated the capacity of hybridization to generate novel (transgressive)
      phenotypes in the taxonomically diverse cichlid fishes. We generated a large F2
      hybrid population by crossing two closely related cichlid species from Lake
      Malawi in Africa with differently shaped heads. Our morphometric analysis focused
      on two traits with different selective histories. The cichlid lower jaw
      (mandible) has evolved in response to strong directional selection, and does not
      segregate beyond the parental phenotype. The cichlid neurocranium (skull) has
      likely diverged in response to forces other than consistent directional selection
      (e.g., stabilizing selection), and exhibits marked transgressive segregation in
      our F2 population. We show that the genetic architecture of the cichlid jaw
      limits transgression, whereas the genetic basis of skull shape is permissive of
      transgressive segregation. These data suggest that natural selection, acting
      through the genome, will limit the degree of diversity that may be achieved via
      hybridization. Results are discussed in the context of the broader question of
      how phenotypic diversity may be achieved in rapidly evolving systems.

PMID- 15856711
TI  - What we have also learned: adaptive speciation is theoretically plausible.
AB  - A recent Perspectives article by Gavrilets (2003) on the theory of speciation
      ignored advances in understanding processes of adaptive speciation, in which the
      splitting of lineages is an adaptation caused by frequency-dependent selection.
      Adaptive, or sympatric, speciation has been modeled since the 1960s, but the
      large amount of attention from both empirical and theoretical biologists that
      adaptive speciation has received in recent years goes far beyond what was
      described in Gavrilets' paper. Due to conceptual advances based on the theory of
      adaptive dynamics, adaptive speciation has emerged as a theoretically plausible
      evolutionary process that can occur in many different ecological settings.

PMID- 15856714
TI  - To bee or not to bee.

PMID- 15856715
TI  - Anaphylaxis.

PMID- 15856716
TI  - Mother follows in daughter's footsteps. Interview by Sue Ridewood.

PMID- 15856717
TI  - Beyond major depression.
AB  - BACKGROUND: The DSM concept of 'major depression' has accrued increased status
      but demonstrated limited utility since inception. METHOD: An historical overview
      of models of depression and the initially perceived advantages presented by the
      concept of 'major depression' are presented before detailing its limitations in
      application. RESULTS: Challenges to the utility of 'major depression' are
      provided by examining its conceptual model, its validity, its utility and the
      limited information generated in aetiological and treatment efficacy studies.
      CONCLUSION: It is argued that the concept of 'major depression' has led to
      sterility in depression research and clinical practice, and that there is a need
      for a paradigm shift in modelling and classifying the depressive disorders.

PMID- 15856718
TI  - DSM criteria for major depression: evaluating symptom patterns using latent-trait
      item response models.
AB  - BACKGROUND: Expert committees of clinicians have chosen diagnostic criteria for
      psychiatric disorders with little guidance from measurement theory or modern
      psychometric methods. The DSM-III-R criteria for major depression (MD) are
      examined to determine the degree to which latent trait item response models can
      extract additional useful information. METHOD: The dimensionality and measurement
      properties of the 9 DSM-III-R criteria plus duration are evaluated using
      dichotomous factor analysis and the Rasch and 2 parameter logistic item response
      models. Quantitative liability scales are compared with a binary DSM-III-R
      diagnostic algorithm variable to determine the ramifications of using each
      approach. RESULTS: Factor and item response model results indicated the 10 MD
      criteria defined a reasonably coherent unidimensional scale of liability.
      However, person risk measurement was not optimal. Criteria thresholds were
      unevenly spaced leaving scale regions poorly measured. Criteria varied in
      discriminating levels of risk. Compared to a binary MD diagnosis, item response
      model (IRM) liability scales performed far better in (i) elucidating the
      relationship between MD symptoms and liability, (ii) predicting the personality
      trait of neuroticism and future depressive episodes and (iii) more precisely
      estimating heritability parameters. CONCLUSIONS: Criteria for MD largely defined
      a single dimension of disease liability although the quality of person risk
      measurement was less clear. The quantitative item response scales were
      statistically superior in predicting relevant outcomes and estimating twin model
      parameters. Item response models that treat symptoms as ordered indicators of
      risk rather than as counts towards a diagnostic threshold more fully exploit the
      information available in symptom endorsement data patterns.

PMID- 15856719
TI  - Latent structure of depression in a community sample: a taxometric analysis.
AB  - BACKGROUND: The latent structure of depression was examined using taxometric
      analysis, a family of statistical procedures designed specifically to test
      whether a given construct is best conceptualized as a distinct category or a
      continuous dimension. METHOD: Data were derived from the Australian National
      Survey of Mental Health and Well-Being, a large epidemiological survey that
      measured the prevalence of the major DSM-IV and ICD-10 mental disorders. Two
      taxometric procedures, maximum covariance (MAXCOV) and mean above minus below a
      cut (MAMBAC), were carried out on a sample of 1933 community volunteers.
      Simulated categorical and dimensional datasets aided in the interpretation of the
      research data. RESULTS: The results of the taxometric analyses in the subsample
      who endorsed at least one symptom of depression were consistent with a
      dimensional latent structure of depression. CONCLUSIONS: The findings of the
      current study suggest that depression, as measured in this subsample, is best
      conceptualized, measured and classified as a continuously distributed syndrome
      rather than as a discrete diagnostic entity. Incorporation of dimensional
      measurement into psychiatric classification systems remains a challenge for the
      future.

PMID- 15856720
TI  - Dimensions and classes of psychosis in a population cohort: a four-class, four
      dimension model of schizophrenia and affective psychoses.
AB  - BACKGROUND: Classification of psychosis lacks a biological basis and current
      diagnostic categories may obscure underlying continuities. Data reduction methods
      of symptom profiles within a population-based cohort of people with a wide range
      of affective and non-affective psychoses may permit an empirical classification
      of psychosis. METHOD: OPCRIT (operational criteria) analysis was performed on 387
      adults aged 18-65 years in an attempted ascertainment of all patients with
      psychosis from a geographical area with a stable population. The data were
      analysed firstly using principal components analysis with varimax rotation to
      identify factors, and secondly to establish latent classes. Information relating
      to key variables known to be of relevance in schizophrenia was coded blind to the
      establishment of the classes and dimensions. RESULTS: Striking correspondence was
      obtained between the two methods. The four dimensions emerging were labelled
      'depression', 'reality distortion', 'mania' and 'disorganization'. Latent classes
      identified were 'depression', 'bipolar', 'reality distortion/depression' and
      'disorganization'. The latent classes corresponded well with DSM-III-R diagnoses,
      but also revealed groupings usually obscured by diagnostic boundaries. The latent
      classes differed on gender ratio, fertility, age of onset and self-harming
      behaviour, but not on substance misuse or season of birth. CONCLUSIONS: Both
      dimensional and categorical approaches are useful in tapping the latent
      constructs underlying psychosis. Broad agreement with other similar studies
      suggests such findings could represent discrete pathological conditions. The four
      classes described appear meaningful, and suggest that the term non-affective
      psychosis should be reserved for the disorganization class, which represents only
      a subgroup of those with schizophrenia.

PMID- 15856721
TI  - Reversed diurnal variation in depression: associations with a differential
      antidepressant response, tryptophan: large neutral amino acid ratio and serotonin
      transporter polymorphisms.
AB  - BACKGROUND: Although diurnal variation of mood is a widely recognized symptom of
      depression, the clinical, neurobiological and psychopharmacological significance
      of this symptom has not previously been reported. METHOD: A total of 195
      depressed out-patients underwent a detailed clinical and neurobiological
      assessment, and were then randomized to treatment with either fluoxetine or
      nortriptyline. RESULTS: Of the 195 depressed patients, 62 had a pattern of
      reversed diurnal variation (i.e. worse in the evening). Those with reversed
      diurnal variation had a poorer response to a serotonergic anti-depressant, were
      less likely to have bipolar II disorder, had a higher tryptophan: large neutral
      amino acid ratio and had different allele frequencies of the polymorphisms in the
      promoter region of the serotonin transporter. CONCLUSIONS: These findings raise
      the possibility of serotonergic influence on diurnal variation, and that the
      symptom of reversed diurnal variation is of relevance to antidepressant
      prescribing.

PMID- 15856722
TI  - The socio-economic status of communities predicts variation in brain serotonergic
      responsivity.
AB  - BACKGROUND: We reported previously that the socio-economic status (SES) of
      individuals predicts variation in brain serotonergic responsivity, as assessed by
      neuropharmacological challenge in an adult community sample, and that this
      association is qualified by allelic variation in the serotonin transporter gene
      linked polymorphic region (5-HTTLPR). Here we examine whether serotonergic
      responsivity covaries similarly with the SES of communities, as indexed by US
      Census data in the same study sample. METHOD: Community SES was defined by levels
      of income, economic disadvantage, housing costs, and educational attainment of
      census tracts in which 249 locally recruited study participants (54% male)
      resided. Serotonergic responsivity was assessed as the baseline-adjusted, peak
      plasma prolactin (Prl) concentration following acute administration of the
      serotonin-releasing agent, fenfluramine; tissue for DNA extraction and 5-HTTLPR
      genotyping was available on 131 participants. RESULTS: Subjects residing in
      census tracts of lower SES showed a blunted Prl response to fenfluramine
      (diminished serotonergic responsivity) relative to individuals living in more
      affluent neighborhoods. When adjusted for personal income and education, SES at
      the community level continued to predict fenfluramine-stimulated Prl responses
      and did so independently of 5-HTTLPR genotype. CONCLUSIONS: Area-level indices of
      relative social and economic disadvantage covary with individual differences in
      brain serotonergic responsivity, and this association is, in part, independent of
      individually defined SES. These findings may be relevant to reported effects of
      low community SES on the prevalence of psychiatric disorders or behaviors
      associated with dysregulation of central serotonergic function, such as
      depression, impulsive aggression, and suicide.

PMID- 15856724
TI  - Self-devaluative dysphoric experience and the prediction of persistent first
      episode major depressive disorder in adolescents.
AB  - BACKGROUND: The quality of subjective experience of dysphoria may predict
      persistence of depression, independently of severity. This is tested in a clinic
      sample of adolescents with first episode of major depression using the Depressed
      States Checklist adapted for adolescents. METHOD: Ninety-four adolescents with
      DSM-IV major depressive disorder (MDD) were followed up at 12 months. Self
      devaluative components of dysphoric experience, ruminative style, over-general
      autobiographical memory, and self-reported and observer-rated measures of
      depression severity were assessed at presentation and evaluated as predictors of
      persistent MDD. RESULTS: Persistent MDD was predicted by the independent additive
      effects of the higher self-devaluative component of dysphoria, lower general
      intelligence and greater observer-rated severity of depression at presentation.
      Neither self-reported depression score, overgeneral memory retrieval nor
      ruminative style contributed. CONCLUSIONS: High levels of self-devaluative
      dysphoric experience increase the liability for persistence of first-episode MDD.
      Other affective-cognitive components also contribute. The adolescent version of
      the Depressed States Checklist is a useful brief measure of cognitive
      vulnerability for persistence in currently depressed young people.

PMID- 15856723
TI  - Relationship of homocysteine, folic acid and vitamin B12 with depression in a
      middle-aged community sample.
AB  - BACKGROUND: Case control studies have supported a relationship between low folic
      acid and vitamin B112 and high homocysteine levels as possible predictors of
      depression. The results from epidemiological studies are mixed and largely from
      elderly populations. METHOD: A random subsample of 412 persons aged 60-64 years
      from a larger community sample underwent psychiatric and physical assessments,
      and brain MRI scans. Subjects were assessed using the PRIME-MD Patient Health
      Questionnaire for syndromal depression and severity of depressive symptoms. Blood
      measures included serum folic acid, vitamin B12, homocysteine and creatinine
      levels, and total antioxidant capacity. MRI scans were quantified for brain
      atrophy, subcortical atrophy, and periventricular and deep white-matter
      hyperintensity on T2-weighted imaging. RESULTS: Being in the lowest quartile of
      homocysteine was associated with fewer depressive symptoms, after adjusting for
      sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in
      the lowest quartile of folic acid was associated with increased depressive
      symptoms, after adjusting for confounding factors, but adjustment for
      homocysteine reduced the incidence rate ratio for folic acid to a marginal level.
      Vitamin B12 levels did not have a significant association with depressive
      symptoms. While white-matter hyperintensities had significant correlations with
      both homocysteine and depressive symptoms, the brain measures and total
      antioxidant capacity did not emerge as significant mediating variables.
      CONCLUSIONS: Low folic acid and high homocysteine, but not low vitamin B12
      levels, are correlates of depressive symptoms in community-dwelling middle-aged
      individuals. The effects of folic acid and homocysteine are overlapping but
      distinct.

PMID- 15856725
TI  - Morphological brain changes associated with Schneider's first-rank symptoms in
      schizophrenia: a MRI study.
AB  - BACKGROUND: Schneider's first-rank symptoms involve an alienated feature of the
      sense of one's own mental or physical activity. To clarify the brain
      morphological basis for the production of these symptoms, volumes of the frontal
      and medial temporal regions and their clinical correlates were examined in
      patients with schizophrenia. METHOD: Twenty-two patients with schizophrenia and
      44 age- and gender-matched healthy control subjects were included. All patients
      were in their psychotic episodes with definite Schneiderian symptoms, rated by
      using the Scale for Assessment of Positive Symptoms. Volumetric measurements of
      high-resolution magnetic resonance imaging were performed in the prefrontal area,
      cingulate gyrus, and precentral gyrus, and the medial temporal structures such as
      the amygdala, hippocampus, and parahippocampal gyrus. RESULTS: Patients had
      significantly decreased volumes in the cingulate gray matter and the amygdala
      compared to controls. In the patient group, Schneiderian symptom severity showed
      significant inverse correlations with volumes of the right posterior cingulate
      gray matter and of the left anterior parahippocampal gyrus. CONCLUSIONS:
      Schneiderian symptoms may be associated with morphological abnormalities in the
      limbic-paralimbic regions such as the cingulate gyrus and parahippocampal gyrus,
      which possibly serve the self-monitoring function and the coherent storage and
      reactivation of information.

PMID- 15856726
TI  - Increased gray-matter volume in medication-naive high-functioning children with
      autism spectrum disorder.
AB  - BACKGROUND: To establish whether high-functioning children with autism spectrum
      disorder (ASD) have enlarged brains in later childhood, and if so, whether this
      enlargement is confined to the gray and/or to the white matter and whether it is
      global or more prominent in specific brain regions. METHOD: Brain MRI scans were
      acquired from 21 medication-naive, high-functioning children with ASD between 7
      and 15 years of age and 21 comparison subjects matched for gender, age, IQ,
      height, weight, handedness, and parental education, but not pubertal status.
      RESULTS: Patients showed a significant increase of 6% in intracranium, total
      brain, cerebral gray matter, cerebellum, and of more than 40% in lateral and
      third ventricles compared to controls. The cortical gray-matter volume was evenly
      affected in all lobes. After correction for brain volume, ventricular volumes
      remained significantly larger in patients. CONCLUSIONS: High-functioning children
      with ASD showed a global increase in gray-matter, but not white-matter and
      cerebellar volume, proportional to the increase in brain volume, and a
      disproportional increase in ventricular volumes, still present after correction
      for brain volume. Advanced pubertal development in the patients compared to the
      age-matched controls may have contributed to the findings reported in the present
      study.

PMID- 15856728
TI  - The Behavioural Responses to Illness Questionnaire (BRIQ): a new predictive
      measure of medically unexplained symptoms following acute infection.
AB  - BACKGROUND: The aim of this study was to design a self-report measure of
      behavioural responses during the acute phase of an illness, in order to assess
      the importance of these behaviours in the development of ongoing medically
      unexplained syndromes. METHOD: An initial pool of items derived from theoretical
      models and clinical observation, was piloted on a group of 312 university
      students to assess the factor structure of the scale and the best fit items. The
      scale was further validated in a second study of 758 patients who were
      experiencing Campylobacter gastroenteritis. At 3 months post-infection, patients
      were sent a second questionnaire assessing symptoms of irritable bowel syndrome
      (IBS). RESULTS: Principal components analysis of the items in the student sample
      yielded a four-factor solution, labelled all-or-nothing behaviour, limiting
      behaviour, emotional support seeking and practical support seeking. The factor
      structure was confirmed in the Campylobacter sample, and internal reliability was
      good. All-or-nothing behaviour was associated with IBS at 3 months post
      infection. In contrast, limiting behaviour and practical support seeking at the
      time of infection appeared to be protective. CONCLUSION: The results suggest that
      this is a valid and reliable measure that can predict the development of a
      medically unexplained syndrome after acute infection. Overdoing things at the
      time of infection and then needing to rest for prolonged periods (all-or-nothing
      behaviour), appears to be a particular risk factor for the development of IBS.
      Targeted interventions at the time of infection may improve coping and prevent
      symptoms from becoming chronic.

PMID- 15856727
TI  - Executive function in Tourette's syndrome and obsessive-compulsive disorder.
AB  - BACKGROUND: Cognitive performance was compared in the genetically and
      neurobiologically related disorders of Tourette's syndrome (TS) and obsessive
      compulsive disorder (OCD), in three domains of executive function: planning,
      decision-making and inhibitory response control. METHOD: Twenty TS patients,
      twenty OCD patients and a group of age- and IQ-matched normal controls completed
      psychometric and computerized cognitive tests and psychiatric rating scales. The
      cognitive tests were well-characterized in terms of their sensitivity to other
      fronto-striatal disorders, and included pattern and spatial recognition memory,
      attentional set-shifting, and a Go/No-go set-shifting task, planning, and
      decision-making. RESULTS: Compared to controls, OCD patients showed selective
      deficits in pattern recognition memory and slower responding in both pattern and
      spatial recognition, impaired extra-dimensional shifting on the set-shifting test
      and impaired reversal of response set on the Go/No-go test. In contrast, TS
      patients were impaired in spatial recognition memory, extra-dimensional set
      shifting, and decision-making. Neither group was impaired in planning. Direct
      comparisons between the TS and OCD groups revealed significantly different
      greater deficits for recognition memory latency and Go/No-go reversal for the OCD
      group, and quality of decision-making for the TS group. CONCLUSIONS: TS and OCD
      show both differences (recognition memory, decision-making) and similarities (set
      shifting) in selective profiles of cognitive function. Specific set-shifting
      deficits in the OCD group contrasted with their intact performance on other tests
      of executive function, such as planning and decision-making, and suggested only
      limited involvement of frontal lobe dysfunction, possibly consistent with OCD
      symptomatology.

PMID- 15856729
TI  - Injury prevention: Part 2.

PMID- 15856730
TI  - An explanation for Wisconsin's high falls rate?

PMID- 15856731
TI  - Society joins effort to prevent physician shortage.

PMID- 15856732
TI  - Cigarette tax increase proposal gains momentum.

PMID- 15856733
TI  - The analogy of the hive.

PMID- 15856734
TI  - Report on a flawed "report card": the public citizens ranking of medical
      licensing boards.
AB  - Any global ranking of states with respect to the health and safety of its
      citizens using specific, singular scales is fraught with difficulty and all such
      efforts should be interpreted with caution. It becomes even more problematic when
      one attempts to link physician discipline rates directly to either quality of
      care or injury and deaths of patients, as the Health Resource Group alleges. Any
      bona fide ranking of states with respect to health care or patient safety
      overall, whatever its source or its attempted correlations, would require a very
      complex, sophisticated equation with multiple, defined, distinct, quantifiable
      variables. The HRG report does not meet that high threshold. First, its report
      ranks states from best to worst using FSMB physician discipline action data
      despite the FSMB disclaimer that none of its numbers should be used to compare
      one state to another. Second, HRG sets up its own selective criteria for
      "seriousness" of discipline, and in so doing specifically excludes the category C
      disciplines, which Wisconsin uses often and responsibly in protecting the public
      and disciplining physicians. This arbitrary exclusion puts Wisconsin into an
      unwarranted "worst" state category. Third, HRG then links its worst states to
      practices that "injure or kill patients." However when one attempts to verify
      such allegations by comparing HRG rankings to specific quality-of-care rankings,
      using such measurements as Medicare data or Hospital HealthGrade data, such a
      sweeping allegation is unsupported. Finally, HRG's conclusion that "more is
      better" with respect to physician discipline rates needs to be examined and
      weighed very carefully. It may be, in fact, that in those states with lower rates
      of physician discipline ("worse" states by HRG standards) there are fewer
      complaints filed per capita in the first place, which would point toward a
      "better" level of practice in those states. Or it may be that a lower ("worse")
      record of disciplines is due to "better," more stringent screening of physicians
      in the initial licensing process, thus keeping out the problem physicians in the
      first place. Or those states with lower discipline rates may have more
      alternative programs and resources such as a voluntary impaired professional
      program, which has stringent monitoring but does not require formal discipline.
      HRG's ranking of Wisconsin as 49th in physician discipline rates is flawed in
      process and in fact. The accusation that such a low rating results in danger to
      patients or "not practicing medicine in the best manner" is an unsupported one.
      Comparison of the HRG ranking system with two other measures of quality of care-
      the Medicare Beneficiaries Quality of Care Study and the HealthGrades Hospital
      Quality in America Study--shows little consistency between those rankings and the
      HRG study. Overall, the Wisconsin Medical Examining Board continues to carry out
      its important mission of patient safety and physician licensing and discipline in
      a very responsible and accountable fashion, and a closer analysis of the Health
      Research Group report, which suggests otherwise, demonstrates it to be a flawed
      "report card".

PMID- 15856735
TI  - Education is not enough: equipment and legislation also needed to prevent injury.

PMID- 15856736
TI  - Injuries can be prevented.

PMID- 15856737
TI  - The epidemiology of traumatic brain injury in Wisconsin, 2001.
AB  - PROBLEM: Traumatic brain injury (TBI) is a leading cause of death and disability
      in the United States. To implement more effective injury prevention and treatment
      programs, it is important to identify the regional impact, causes, risk factors,
      and trends of TBI. This report summarizes the public health impact of TBI in
      Wisconsin. METHODS: Data on fatal and non-fatal TBI injuries in Wisconsin in 2001
      were obtained from 2 separate data sources: National Center for Vital Statistics
      and the Wisconsin Bureau for Health Information. Rates of fatal and nonfatal TBI
      were calculated using 2000 population estimates as denominators. RESULTS: There
      were 1059 TBI fatalities and 4006 living TBI-related hospital discharges in
      Wisconsin in 2001. The overall rate of TBI in Wisconsin for 2001 was 94.4 per
      100,000 people. The number of fatal and nonfatal TBI related injuries was higher
      for males than females, at all ages, except nonfatal injuries in persons older
      than 65 years. Fatalities from TBI were highest in young adults and the elderly.
      CONCLUSIONS: TBI is a major cause of death and hospitalizations in Wisconsin.
      Male teens and young adults, and the elderly are high-risk groups for TBI.
      Preventive measures should be aimed at these high-risk groups.

PMID- 15856738
TI  - Geographic analysis of traffic injury in Wisconsin: impact on case fatality of
      distance to level I/II trauma care.
AB  - PURPOSE: Traffic injuries are an important public health problem in Wisconsin.
      This paper examines geographic variations in the incidence and case fatality of
      traffic injuries, and evaluates proximity to Level I/II trauma care as a
      predictor of case fatality. METHODS: Data on all persons injured in motor vehicle
      crashes on Wisconsin roadways during a 10-year period (1992-2001) were obtained
      from the Wisconsin Crash Outcome Data Evaluation System. Injury rates per 100
      million vehicle miles traveled (VMT) and case fatality were visually displayed by
      county. Multiple logistic regression models were used to evaluate distance
      between crash site and Level I/II trauma care as a risk factor for fatality,
      controlling for other factors. RESULTS: During the 10-year period, 50,300 people
      were severely injured in motor vehicle crashes and 7450 (15%) died. Injury rates
      per VMT were highest in the southeast counties. In contrast, case-fatality for
      all injuries and for severe injuries was highest in northern and western counties
      and significantly associated with distance from Level I/II trauma care after
      controlling for other predictors of case fatality. CONCLUSIONS: Strategies are
      needed to reduce the disparity in traffic injury case fatality across the state
      and to improve outcomes for persons injured in counties distant from Level I/II
      trauma care.

PMID- 15856739
TI  - The perils of snowmobiling.
AB  - Snowmobiling is a popular winter sport in Wisconsin, but it can result in serious
      injury and death. From 1998-2002, 1090 people in Wisconsin were hospitalized due
      to injuries related to snowmobiling. From 2002 to 2004, 51 snowmobile-related
      fatalities were reported to the Wisconsin Department of Natural Resources.
      Multiple risk factors exist for snowmobile injury and death, with alcohol
      consumption and male gender being the 2 largest associated risks. Many of the
      risk factors are modifiable, and health care professionals can facilitate
      snowmobiling-related injury prevention.

PMID- 15856740
TI  - The role of the health care professional in bicycle safety.
AB  - Learning to ride a bicycle and enjoying the pleasures of cycling are synonymous
      with childhood; unfortunately, cycling does not come without risk of serious
      injury. Children under 15 years old account for the majority of cycling time in
      the United States, and on average, 1 child dies every day from a bicycle-related
      injury. Health care professionals can play an important role in making cycling a
      safe activity by encouraging and advocating for safe bicycling practices.
      Specific areas for physicians and health care professionals to emphasize involve
      the cyclist, environmental factors, and equipment factors. Helmet use by
      cyclists, avoidance of risk-taking, safe cycling road behavior, and proper
      cycling equipment fit and usage are all areas in which health care professionals
      can instruct families during office visits. The physician and the health care
      community can also be advocates for mandatory helmet legislation in order to
      achieve higher helmet usage rates and decreased cycling injuries. The health care
      professional's role in bicycle safety is an important component in building a
      foundation for safe cycling.

PMID- 15856741
TI  - Increased risk of death or disability in unhelmeted Wisconsin motorcyclists.
AB  - OBJECTIVE: The purpose of this study is to investigate the relationships among
      motorcycle rider helmet, alcohol use and the full spectrum of health outcomes
      following crashes. METHODS: Data from the National Highway Traffic Safety
      Administration-sponsored Crash Outcome Data Evaluation System (CODES) for
      Wisconsin, 2002, were used to study 2462 motorcycle crash victims. Logistic
      regression models were used to assess the relationship of helmet and alcohol use
      with outcomes. RESULTS: Compared to helmeted motorcycle riders, unhelmeted riders
      were more likely to require inpatient hospitalization (Relative Risk Ratio [RRR]
      = 1.4; 95% confidence interval [CI]:1.1-1.8) or die (RR = 1.9, 95% CI:1.0-3.7)
      but equally likely to be treated in emergency departments. Injury patterns
      differed by helmet use. Unhelmeted riders were more likely to suffer injuries of
      the head (odds ratio [OR] = 2.3, 95% CI:1.5-3.3) or face (OR = 3.0, 95% CI:2.1
      4.2) than helmeted riders. No difference was observed in other injuries,
      including spine/neck injuries. Reported alcohol use was more prevalent among
      patients who were inpatients or died, and was associated with higher likelihood
      of not wearing a helmet (OR = 7.0, 95% CI:4.8-12.9). CONCLUSION: Motorcycle
      riders who are inpatients or die in a crash are less likely to be helmeted and
      more likely to sustain head or face injuries. Alcohol use is associated with
      unhelmeted riding and increased risk of poor outcomes. These findings support
      policy and educational efforts promoting helmet use, which seek to decrease these
      tragedies.

PMID- 15856742
TI  - Promoting childhood water safety: the physician's role.
AB  - Injuries and deaths secondary to drowning are a significant issue for children.
      The risks associated with drowning change with a child's age and developmental
      abilities. Nationally, children under the age of 4 years and male adolescents
      represent the pediatric groups with the highest rates of drowning. In Wisconsin,
      1998-2002, preteen children were involved in drowning or near-drowning events
      more often than teens, with boys being involved more than 2 times as often as
      girls for all childhood ages assessed. The drowning gender disparity is even
      greater among adults. Physicians are in a position to promote water safety for
      their patients and the community by educating families on age-appropriate
      drowning-prevention methods, supporting community safety campaigns, and
      advocating for "best practice" drowning-prevention legislation. Although injury
      prevention anticipatory guidance is important for all family members, directing
      the message to males is particularly important. Physicians can help children
      enjoy the benefits of water recreation while decreasing the risk for water
      associated injury.

PMID- 15856743
TI  - Horse-related injuries in children: a review.
AB  - Horseback riding is an increasingly popular activity among today's youth,
      providing them with the opportunity to learn responsibility and respect for
      animals. However, it can also be associated with severe injury, of which many
      physicians are unaware. In 2002, there were an estimated 13,400 emergency
      department visits nationwide for horse-related injuries among children younger
      than 15 years. When using a severity score to compare it with other childhood
      injuries, equestrian-related injury ranked second only to pedestrians being
      struck by a car, and had a higher score than all terrain vehicle, bicycle, and
      passenger motor vehicle crash injuries. Most serious injuries occur when a rider
      is thrown from a horse, which is often accompanied by being dragged or crushed by
      the horse. However, hoof kick injuries to an unmounted child represent about 30%
      of horse-related injuries and may result in more severe injury. Head injury is
      the injury most likely to result in hospitalization or death. The effectiveness
      of helmets in preventing serious head injury in horse-related accidents has been
      very well established. Recommendations for the prevention of horse-related injury
      include requiring helmet use on and near a horse, use of safety stirrups to
      prevent drag injury, matching rider skill with the appropriate horse, and
      providing close adult supervision.

PMID- 15856745
TI  - Managing an IRA inheritance.

PMID- 15856744
TI  - Much more research needed on injury prevention.

PMID- 15856746
TI  - [Symposium entitled "psychopathology of the aged"--the development since then].

PMID- 15856747
TI  - [A deficit in preattentive processing of visual information in schizophrenic
      patients].
AB  - Schizophrenia is associated with deficits in information processing. Several
      studies have shown impairments in attentional functions of visual perception in
      schizophrenic patients. Attentional function is thought to consist of two stages;
      preattentive processing and attentive processing. Preattentive processing enables
      an individual to detect a target without scanning stimuli one by one. The search
      time is almost constant as distoractors increase. On the other hand, attentive
      processing needs sequential scanning of stimuli to detect a target. Here, the
      search time increases as distractors increase. In this paper, preattentive
      information processing was investigated in 30 schizophrenic patients and 30
      control subjects using visual search tasks. Subjects were instructed to find a
      target and press a button in two kinds of visual search tasks. The figures of
      tasks were constructed with one 'L' and 5, 17, 35 'X's in the high-pop-out task,
      and one 'L' and 5, 17, 35 'T's in the low-pop-out task. The performance of the
      high-pop-out task requires preattentive processing. The time to push the button,
      the time for the viewpoint to reach the target and the direction of the first
      saccade were recorded using the eye-mark recorder. The reaction time to push the
      button in schizophrenics was generally longer than that in controls, irrespective
      of the levels of pop-out. In addition, the time for the viewpoint to reach the
      target was also greater in schizophrenics. Also, in the direction of the first
      saccade, schizophrenics showed a lower rate of making the first saccade toward
      the target than controls in the high-pop-out task. In conclusion, the present
      results suggests that there is some kind of deficit in preattentive processing of
      visual information in schizophrenic patients.

PMID- 15856748
TI  - [Progress in neuroscience and image diagnosis of epilepsy].

PMID- 15856749
TI  - [Epileptic seizures or pseudo-seizures?].

PMID- 15856750
TI  - [Psychiatric symptoms of epilepsy--physiopathology and differential diagnosis].

PMID- 15856751
TI  - [Epilepsy and legal problems--with special reference to the issuance of
      automobile driving license].

PMID- 15856752
TI  - [Clinical aspect of epileptic psychosis--based on the observation of our cases].

PMID- 15856754
TI  - [Psychiatric symptoms of Parkinson's disease--an overview from the studies on
      dopaminergic nerves].

PMID- 15856753
TI  - [Genetically modified animals as models for psychiatric diseases].
AB  - Animal models of mental disorders as well as physical disorders have been useful
      tools to elucidate pathophysiology of the complex disorders and develop new
      therapeutics. Transgenic mice including gene knockout animals have been produced
      by gene targeting technology. Monoamine system which is target of antipsychotics
      and antidepressants has very important roles in pathology of functional
      psychosis. In this review, we would like to introduce monoamine transporter
      knockout mice that we had generated as animal models of mental disorders
      including schizophrenia and drug abuse.

PMID- 15856755
TI  - [Etiology and pathogeneses of Guillain-Barre syndrome and related diseases:
      focusing on anti-gangliosides antibody].

PMID- 15856756
TI  - [Impairment of social cognition in Parkinson's disease].
AB  - The characteristic four symptoms of motor deficits, bradykinesia, rigidity,
      resting tremor and impairment of postural reflex with Parkinson's disease (PD)
      are accompanied by specific cognitive deficits. Deficits of executive functions,
      skill learning, and visuospatial cognition are well known. The results of our
      recent studies show the deficit of social cognition which include facial
      expression recognition, sensation of gaze direction, "theory of mind" in
      comprehension, and decision making. These symptoms can be explained by the damage
      of the amygdala and/or its connection, which are known to play a crucial role in
      social cognition, it is attributed to the involvement of amygdala and it's
      connection to the frontal lobe in PD. The impairment of social cognition is an
      important mental change associated with PD.

PMID- 15856757
TI  - [The clinical utility of MR diffusion tensor imaging and spatially normalized PET
      to evaluate traumatic brain injury patients with memory and cognitive
      impairments].
AB  - We detected and compared abnormal brain areas using both MR diffusion tensor
      imaging (DTI) and easy Z score imaging system (eZIS) of FDG-PET for traumatic
      brain injury patients with memory and cognitive impairments. Twenty normal
      subjects and eighteen diffuse axonal injury patients with memory and cognitive
      impairments were studied with DTI and eZIS of 18F-FDG-PET. DTI contained
      fractional anisotorophy (FA) analysis and the tractography for the corpus
      callosum. After PET imaging was performed, statistical analysis using eZIS was
      undergone with followed processing steps, including smoothing, normalization and
      z transformation with respect to normal database. Z score map was superimposed on
      3D MRI brain. Group analysis was performed using SPM. In diffuse axonal injury
      patients, the decline of FA was observed around the corpus callosum in comparison
      with normal subjects and the reduction of glucose metabolism was shown in the
      cingulated association. These results suggest that the reduction of metabolism
      within the cingulated cortex indicated deprived neuronal activation caused by the
      impaired neuronal connectivity that was revealed with DTI. Furthermore, the
      metabolic abnormalities within the cingulated cortex may be responsible for
      memory and cognitive impairments. DTI and spatially normalized PET have a role in
      neuroimaging interpretation for patients with memory and cognition impairments
      because its 3D better visualization allows objective and systematic
      investigation.

PMID- 15856758
TI  - [Distribution of ischemic leukoaraiosis in MRI: a difference from white matter
      lesions in CADASIL].
AB  - Previously, the distribution of white matter lesions in CADASIL has been reported
      to be distinct from those in patients with ischemic leukoaraiosis and
      Binswanger's disease. In earlier European studies, diagnostic significance of
      white matter lesions in the temporopolar region (Tp), medial frontopolar region
      (Fp) and external capsule (EC) was stressed in diagnosing CADASIL. More recently,
      however, high sensitivity and specificity of Tp lesions have been demonstrated.
      In Japan, prevalence of CADASIL is lower, and those of ischemic leukoaraiosis and
      Binswanger's disease, likely related to small artery disease, are much higher
      than in Caucasian countries. Therefore, we examined the frequencies of CADASIL
      associated lesions in 17 non-demented patients with ischemic leukoaraiosis and 20
      patients with Binswanger's disease. The Binswanger's disease group showed a
      significantly lower scores for Hasegawa Dementia Rating Scale Revised (HDSR) and
      a higher prevalence of hypertension, compared to the ischemic leukoaraiosis
      group. There was only 1 patient with Tp lesions in each group, while Fp lesions
      were found in 12 % and 50% in the ischemic leukoaraiosis group and Binswanger's
      disease group, respectively, and EC lesions in 59% and 80%. These results
      indicated that Tp lesions were useful diagnostic marker in diagnosing CADASIL,
      whereas Fp and EC lesions were non-specifically observed.

PMID- 15856759
TI  - [Cerebral hemodynamics in adult ischemic-type patients with moyamoya disease
      compared with those of atherothrombotic middle cerebral artery occlusion].
AB  - We measured regional cerebral blood flow (rCBF) in adult ischemic-type patients
      with moyamoya disease and in patients with atherothrombotic middle cerebral
      artery occlusion (MCAO) to investigate cerebral hemodynamics in adult ischemic
      type of moyamoya disease. In this study we measured rCBF and regional
      cerebrovascular response (rCVR) using acetazolamide by Xenon-enhanced CT. Our
      subjects consisted of 15 adult ischemic-type patients with moyamoya disease and
      27 atherothrombotic stroke patients with proximal occlusion of the middle
      cerebral artery. The region of interest was conducted in the anterior cerebral
      artery, middle cerebral artery and posterior cerebral artery territories as well
      as basal ganglia regions. rCBF was preserved in all regions of patients with
      moyamoya disease. However, rCVR severely decreased in the anterior circulation
      territory in patients with moyamoya disease compared with those of MCAO. These
      results suggest that rCBF in the anterior circulation territory of adult ischemic
      type patients with moyamoya disease is preserved by vasodilation of the cerebral
      arteries, while cerebral hemodynamic reserve capacity is severely reduced. The
      results indicated that basal moyamoya vessels are dilated. These findings may be
      one of the reasons why stroke occurs more frequently in adult than child patients
      with moyamoya disease.

PMID- 15856760
TI  - [Clinical application of Japan Stroke Scale Higher Cortical Function (JSS-H)].
AB  - To clarify the characteristics of Japan Stroke Scale Higher Cortical Function
      (JSS-H), we compared the results of JSS-H with those of Revised Hasegawa Dementia
      Scale (HDS-R), on the 47 patients with cerebrovascular disease visiting to the
      day-care center of the Yoshinaga Municipal Hospital. The scores of the two scales
      significantly correlated. Especially, among the patients who gained over 21
      points (non-dementia) in HDS-R, the results of both scales were almost parallel,
      but among those who gained less than 20 points(dementia), the scores showed some
      discrepancy. Most of the patient with discrepancy had higher scores in JSS-H than
      in HDS-R, and were independent in their daily life despite of their memory
      disturbance. These results suggest that JSS-H can assess more global cerebral
      function than HDS-R and will be useful for estimating the characteristics of the
      higher cortical function of the patients, although it has some problems to be
      solved for clinical application.

PMID- 15856761
TI  - [Treatment of neurological complication due to postgastrectomy vitamin E
      deficiency].
AB  - Although postgastrectomy vitamin E deficiency rarely occurs, it can cause
      neuromuscular disorder such as neuropathy, myopathy and cerebellar ataxia. We
      encounter a lot of cases whose serum vitamin E level were decreased after
      gastrectomy. We evaluated the oral vitamin E intake as a therapy to these cases.
      The subjects of this study were 11 gastrectomized patients (8 patients had total
      gastrectomy, 2 subtotal gastrtectomy, 1 partial gastrectomy) with decreased
      vitamin E. 10 patients had neurological complications such as dizziness,
      dysesthesia, truncal ataxia. Serum vitamin E increased to normal level in 10
      patients and neurological disturbances were improved in 9 patients. The minimum
      requirement of oral vitamin E intake was 150 mg a day for normalization of serum
      vitamin E, on the other hand, it decreased with 150 mg intake in some patients.
      Their serum level increased with 300 mg. We suggest that it is important to check
      serum vitamin E in gastrectomized patients and oral vitamin E should be supplied
      over 300 mg for the therapy with vitamin E deficiency.

PMID- 15856762
TI  - [The therapeutic efficacy in Fisher syndrome].
AB  - We studied clinical courses of 15 cases of Fisher syndrome (FS) and examined
      therapeutic efficacy of plasma exchange (PE), immunoadsorption (IA), intravenous
      immune globulin (IVIg), and steroid therapy (ST). Compared with other treatments,
      PE and IA had shortened the peak period of the symptoms, but had not revealed the
      difference of the duration of illness between one another. As for PE and IA, the
      short-term effect was seen, but did not show the long-term effect. Though IVIg
      was done at the early stage, it did not shorten the peak period. So we conclude
      IVIg for FS to be effective not so equal as PE. However, clinical manifestations
      were milder in IVIg cases than PE, and there was a possibility that the symptoms
      of FS became mild by early treatment with Mg. Compared with Guillain-Barre
      syndrome, it is rare for FS to leave aftereffects and convalescence is good, so
      the choice of a therapy should be considered with a severity and complications.

PMID- 15856764
TI  - [Sulcal hyperintensity on FLAIR imaging in bacterial meningitis].

PMID- 15856763
TI  - [Targeted small craniotomy and evacuation for subscute subdural hematomas:
      technical report of two cases].
AB  - The etiology and proper treatment of symptomatic subacute subdural hematomas
      remains to be elucidated. We describe two cases of this entity successfully
      treated with small craniotomy and evacuation. Both patients initially treated
      conservatively for traumatic thin subdural hematomas because of poor medical
      condition and mild neurological symptoms, but suffered abrupt neurological
      deterioration between 2 and 3 weeks after the admission. CT scan showed decreased
      density of hematomas with minimal increase in volume, and significant swelling of
      ipsilateral cerebral hemisphere. Urgent two-burr-hole small craniotomy was
      effective for evacuation of partially organized hematoma. During surgery,
      definite hematoma membrane was not confirmed. Postoperatively, brain swelling
      rapidly disappeared and both patients discharged ambulatory without neurological
      deficit. The present cases are a reminder of this peculiar type of hematoma in
      patients with delayed neurological deterioration after nonsurgical management of
      acute subdural hematoma. The rationale for use of small craniotomy is discussed
      in terms of current understanding of pathogenetic mechanism for this unusual
      condition.

PMID- 15856765
TI  - [Orofacial pain management in dentistry].

PMID- 15856766
TI  - [A basic study on newly developed light-curing resins--Fitness, flexural
      properties and bond strength to self-curing resins].
AB  - The objectives of this study were to evaluate fitness, bending properties, and
      bond strength of newly developed light-curing denture base resins (Eclipse,
      Dentsply) in contrast with conventional heat-curing denture base resins (Acron,
      GC). These evaluations were performed by fitting tests, bending strength tests,
      and shear bond strength tests. For the fitting test, 40 resin specimens, 20 for
      each resin, were made on plaster models, which simulated the maxillae edentulous
      ridge. The gaps between resin specimens and the plaster model were measured. The
      bending strength tests were carried out using 16 resin plate specimens (65 x 10 x
      2.5 mm). The bending strength and elastic modulus for each denture base resin was
      calculated. For the shear bond strength test, self-curing resins were bonded to
      each resin and in total, 32 bonded specimens (20 x 4 x 2.5 mm) were made. The
      shear bond strength tests were carried out in order to evaluate the bond strength
      between the self-curing resin and each denture base resin. The results of these
      tests revealed that Eclipse exhibited better fitness to the plaster model, larger
      bending strength, and larger elastic modulus than Acron. Furthermore, the bond
      strength of Eclipse to self-curing resin was equivalent to that of Acron. These
      results suggest that Eclipse has excellent properties for application in clinical
      settings.

PMID- 15856767
TI  - [Intracanal aspiration technique for root canal irrigation: evaluation of smear
      layer removal].
AB  - A new irrigation technique (intracanal aspiration technique, IAT) was developed
      to minimize the extrusion of root canal irrigant. Fifteen instrumented canals of
      extracted canines were divided into one control and four experimental groups of 3
      teeth each. Each root was fixed in a case and surrounded with colored saline agar
      to measure the meter value of the Root ZX and to evaluate the extrusion of the
      irrigant. In control teeth, no irrigation was performed. In Groups 1 and 2, the
      root canal was irrigated using IAT with an aspiration needle placed 2 or 3 mm
      short of the apex. In Groups 3 and 4, the root canal was irrigated in a
      conventional manner with a washing needle placed 2 or 3 mm short of the apex. The
      file folder of a Root ZX was attached to the aspiration needle in Groups 1 and 2,
      and to a washing needle in Groups 3 and 4. Each canal was irrigated with 9 ml of
      14% EDTA solution and 6 ml of 6% NaClO in experimental groups, and the meter
      value of the Root ZX during irrigation was recorded. After the irrigation,
      cleanliness of the canal was evaluated using a SEM and extrusion of NaClO by
      discoloration of the agar. Irrigation using IAT was more effective for removing
      smear layer compared to the conventional method and extrusion of the irrigant was
      minimized. In addition, the Root ZX measurement during IAT could monitor the
      extent of the irrigant in the apical canal.

PMID- 15856768
TI  - [Growth pattern of the frontal bone primordium and involvement of Bmps in this
      process].
AB  - The mammalian skull vault consists of several membrane bones with different
      origins. A pair of frontal bones, which occupies the anterior part of the skull
      vault, is derived from cranial neural crest cells. The frontal bone primordium
      develops at the superciliary ridge region, then expands towards the top of the
      head. In this study, we investigated the growth pattern of the frontal bone
      primordium and the factors involved in this process. In situ hybridization of
      fibroblast growth factor receptor 2 and Runx2, which are markers of
      preosteoblast, revealed that the frontal bone primordium appears around embryonic
      day 12.5 (E 12.5) and actively grows between E 14 and E 16. We labelled the head
      mesenchyme of E 13 at the superciliary ridge with DiI by ex-utero surgery and
      found that the labelled cells were present at the apical edge of the developing
      frontal bone on E 18. To elucidate the molecular basis of this formation, we
      cultured E 15 calvarium in the presence of recombinant human bone morphogenetic
      proteins (rhBMPs); rhBMP-2 and rhBMP-7, but not rhBMP-4, accelerated the growth
      of the frontal bone domain. These results suggest that the frontal bone
      primordium grows intrinsically by expanding the primordium not by recruiting
      surrounding cells, and Bmp-2 and -7 play roles in stimulating the growth of the
      frontal bone primordium.

PMID- 15856769
TI  - [A study of measurements of and factors influencing threshold levels of taste
      perception].
AB  - The threshold levels of taste perception on the right and left side of the tip,
      root of tongue and soft palate in 60 healthy volunteers were measured by means of
      an electrogustometry test and a filter-paper disk taste test to confirm the
      following hypotheses: (1) the threshold on the tip of the tongue was lower than
      those of the root of the tongue and soft palate, (2) there was a different
      threshold level between sweet, salty, sour and bitter tastes on the tip of the
      tongue, (3) some personal properties influenced the person's threshold. Measured
      threshold levels were compared between these six locations with multiple
      comparisons. Factors influencing the threshold level on the tip of the tongue,
      thereafter, were investigated using multivariate logistic regression models.
      Those factors included sex, age, serological, psychological and behavioral
      factors. As a result, the thresholds levels on the tip of the tongue were
      significantly lower than the root of the tongue and soft palate. The thresholds
      for sweet and bitter taste on the tip of the tongue were also lower than those
      for salty and sour taste. Increase of age, male, serological increase of zinc and
      usual alcohol drinking were identified as factors of increase for several
      thresholds, and increase of anxiety was identified as a factor of decrease for
      two thresholds of four tastes (sweet, salty, sour and bitter) on the tip of the
      tongue in the logistic regression models. Increase of depression, mouth
      breathing, habitual tonus of the tongue and smoking did not appear to be
      influential factors.

PMID- 15856770
TI  - [Regulation of p21(WAF1/CiP1) expression during cellular differentiation].
AB  - In the present study, the molecular mechanisms regulating p 21(WAF1/CiP1)
      expression by basic helix-loop-helix (bHLH) factors during cellular
      differentiation were investigated. The cyclin dependent kinase inhibitor p 21
      plays crucial roles during differentiation of osteoblasts and myoblasts. In the
      osteoblastic cell line MG 63, expression of the p 21 gene has been shown to be
      upregulated by E2A factors, members of the bHLH factor family. In addition, E2A
      dependent activation of p21 promoter can be inhibited by another bHLH factor,
      TWIST. Using reporter assays with mutant p 21 promoters, a novel element was
      identified in the p21 promoter, which is essential for E2A-dependent activation
      and TWIST-mediated inhibition. Interestingly, in the myoblastic cell line C2C12,
      this sequence was not involved in E2A-dependent activation of p21 expression. Gel
      mobility shift assays showed a specific complex of the novel p21 promoter element
      with nuclear factor(s) of MG 63 cells. Complex formation was inhibited by the
      addition of anti-TWIST antibody. In contrast no complexes could be identified
      with C2C12 cells. These results raise the possibility that interactions of the
      bHLH factors with the novel p21 promoter element are cell type specific. This
      suggests a novel mechanism regulating p 21 expression.

PMID- 15856771
TI  - [The relationship between diffuse noxious inhibitory control effects and the
      magnitude of noxious stimuli].
AB  - Diffuse noxious inhibitory control (DNIC) is a phenomenon by which the effect of
      noxious stimuli is inhibited by heterotopic noxious stimulation. We investigated
      whether heterotopic conditioning stimuli could modify the second component of EMG
      activities of the biceps femoris reflex (C-fiber reflex) with different levels of
      intensity. Forty-two adult male anesthetized Wistar rats were divided into 6
      groups with 6 or 8 rats in each. Three groups (8 rats in each group) were
      stimulated with 3 intensity levels of the electrical test stimuli, 1.2 T, 2.0 T,
      or 3.0 T (times the C-fiber reflex threshold), respectively. Conditioning stimuli
      (pinch) were delivered to the upper lip of each rat. Test stimuli were delivered
      to the digits of the hindpaw. Another 3 groups (6 rats in each group) as control
      groups were given similar test stimuli without conditioning stimuli. The
      inhibitory magnitudes of C-fiber reflex activities between the control and lip
      pinch were 215.5 +/- 105.5, 277.7 +/- 159.1, 462.3 +/- 407.9 microV x ms in group
      1.2 T, 2.0 T, and 3.0 T, respectively. The inhibitory magnitudes of C-fiber
      reflex activities in group 3.0 T at pinch were significantly increased compared
      with group 1.2 T and 2.0 T. The present study demonstrated that the C-fiber
      reflexes were inhibited by conditioning stimuli with 3 different levels of test
      stimuli under sevofurane anesthesia. Though it has been considered that DNIC
      effect does not depend on test stimulus intensity, the present study suggested
      that DNIC effect might be affected by the intensity of test stimuli.

PMID- 15856772
TI  - [The questionnaire survey on oral malodor and teeth stains of male high school
      students].
AB  - This study investigated the oral health awareness of aesthetic problems among
      adolescents. In 2002, a questionnaire survey on oral malodor and teeth stains was
      conducted at a junior and senior high school for males in Tokyo. The subjects
      were 783 students. The following results were obtained. (1) The rate of students
      who were concerned about other persons' oral malodor was significantly higher for
      the students in the senior high school than in the junior high school. The
      attitudes toward oral malodor varied depending on whether the target was family
      or friends. (2) Forty percent of junior high school students and first-year
      senior high school students answered that they had been conscious about their
      oral malodor. The rate was 60% for second- and third-year senior high school
      students. There was a significant difference between the two groups. (3) Thirty
      five percent of the students who were conscious about their oral malodor felt
      some difficulties in daily life such as communication with other persons. (4)
      Fifty percent of the students replied that they had been conscious about their
      teeth stains. However, most of them felt no difficulties in daily life. From
      these results, it was revealed that almost half of the junior and senior high
      school students had been concerned about oral malodor and teeth stains. It is
      necessary to provide adequate dental health education on oral malodor and teeth
      stains for students through school oral health promotion activities as well as in
      dental clinics.

PMID- 15856773
TI  - [Development and cell dynamics of PLCbeta2 positive cells in mouse taste buds].
AB  - Taste buds, the sensory end organs for the sense of taste, consist of taste
      sensing cells, supportive cells and basel cells. Taste bud cells are
      heterogeneous in terms of morphology as well as functional profiles. Although the
      lineage of mammalian taste bud cells is largely unknown, it is generally accepted
      that undifferentiated epithelial basal cells surrounding taste buds enter the
      taste buds to form and maintain this specialized corpuscle. To analyze taste bud
      formation during development, we conducted morphological observations and
      examined differentiation marker expression. Thickening of epithelia starts at 13
      dpc foetus and immunohistochemistry against a neural marker, PGP 9.5, revealed
      that the change of epithelial morphology precedes neural projection observed at
      14 dpc foetus. Taste sensing cells appear 6 days after birth indicated by
      expression of the single transduction component phospholipase Cbeta2 (PLCbeta2)
      as differentiation marker. To further investigate the maintenance and cell
      lineage in the taste buds in adults, we injected 5'bromo-2'deoxyuridine (BrdU)
      solution to young growing mice for a week. BrdU label retaining cells (LRCs)
      could be observed even 8 weeks after injection. LRCs were examined the
      differentiation by PLCbeta2 and proliferative activity by Ki-67. The results
      suggested two possibilities. (1) Part of PLCbeta2 positive cells retain
      proliferative activity and multipotentiality, or (2) precursor cells (stem cells)
      stay in the taste buds and produce at least part of the taste sensing cells
      through proliferation and differentiation processes.

PMID- 15856774
TI  - [Educative effect of feedback after medical interview in objective structured
      clinical examination].
AB  - OBJECTIVE: Objective Structured Clinical Examination (OSCE) is widely used to
      assess the core competency of dental residents. However, the educative effect of
      feedback in OSCE has not been fully examined. Therefore, we investigated the
      educative effect of formative feedback in a medical interview station. METHODS:
      The subjects were 51 residents in the clinical training course of our dental
      hospital. After completing the medical interview station, residents were
      individually given formative feedback by evaluators and standardized patients.
      Two months later, residents were asked to fill in a questionnaire about the
      contents of feedback and self-rating mental strain level during OSCE. Videotaped
      performance and feedback were reviewed by investigators to check the answers to
      the questionnaire. RESULTS: Evaluators provided an average of 3.1 feedback items,
      and standardized patients provided an average of 1.6 feedback items for each
      resident. However, each resident remembered an average of 1.3 feedback items from
      evaluators and 0.9 from standardized patients. The lower the score of residents
      in the medical interview station, the more feedback items were given to
      residents. A significant negative correlation was found between the score of
      evaluators and self-rating mental strain level (Spearman rho = -0.326, p =
      0.019). CONCLUSION: For effective feedback, evaluators or standardized patients
      should focus on 2 to 3 items of essential points in OSCE. Repetition of feedback
      using videotaped performance may be useful to improve communication skills for
      medical interview.

PMID- 15856775
TI  - [Career history and perceptions of dental hygiene education programs-
      questionnaire mail-in survey of alumni of the School of Dental Hygiene in Tokyo
      Medical and Dental University].
AB  - This study was conducted to investigate the career history and perceptions about
      dental hygiene education programs among the alumni (1952-1999 graduates) of the
      School of Dental Hygiene in Tokyo Medical and Dental University. A questionnaire
      containing demographic, practice characteristics and views on the programs was
      mailed to 997 alumni in 1999, and 576 alumni (57.8%) responded. Three hundred and
      forty-one respondents worked as dental hygienists. The majority who responded
      were in clinical practice. One hundred and thirty-one of the respondents worked
      in private clinics, 76 in public health centers, and 72 in clinics in companies.
      The rate of them who worked in public health centers was much higher than the
      national average cited in the Statistical Report on Public Health Administration
      and Services. Two hundred and ninety-one respondents reported inadequate
      programs. The rate of them who reported inadequate programs was significantly
      higher in alumni who were working than in alumni who were not. The items cited as
      insufficiently taught at the school were clinical practice, instrumentation,
      foreign language, psychology, counseling, and nursing related subjects. Thus,
      many alumni suggested the need for better programs and continuing education. From
      these results, it was suggested that dental hygienists need to change their
      education programs in order to meet the present and future needs of more
      diversified society. This view was particularly prevalent among alumni who were
      working. The result showed that dental hygiene educators and dental hygienists
      urgently need to reconsider the professionalism of their field.

PMID- 15856776
TI  - [Age-related changes in renewal of taste bud cells and expression of taste cell
      specific proteins in mice].
AB  - It is known that taste sensitivities change throughout life and they decline with
      aging. We have also found that both detection and recognition thresholds of taste
      were significantly elevated in aged persons, while oral somatic sensations hardly
      changed. To elucidate the peripheral mechanisms of the decline of taste
      sensitivities with age, we first investigated age-associated changes in cell
      renewal of taste buds in the circumvallate papillae of ddY mice, because one of
      the major characteristic differences of taste receptors from somatosensory
      receptors is a continual turnover of cells. In addition, we examined the
      expression patterns of taste cell-specific proteins such as protein gene products
      9.5 (PGP 9.5) and gustducin, and ultrastructure of taste buds which may change
      resulting from the change of turnover rate. As a reference, we also used mice in
      the developing stage. The rate of cell renewal was examined using 5-bromo-2'
      deoxyuridine (BrdU), which is incorporated in DNA during the S-phase of cells.
      BrdU and the proteins were detected immunohistochemically and the ultrastructure
      was investigated by electron microscopy. The aged mice demonstrated a delayed
      cell renewal and highly vacuolated cytoplasm in taste buds, while they showed no
      change in PGP 9.5-immunoreactive cells and an increase in gustducin
      immunoreactive cells compared with young adult mice. In contrast, the developing
      mice showed a higher rate of cell turnover and rapid increase of PGP 9.5- and
      gustducin-immunoreactive cells reaching the mature level in 3 weeks after birth.
      The changes observed in the present study in aged mice may be related to the
      decline in taste sensitivity with aging.

PMID- 15856777
TI  - [The effect of platelet-rich plasma combined with autogenous bone graft for bone
      regeneration in bone defects].
AB  - The objective of the present study was to evaluate the effect of PRP on bone
      healing both quantitatively and qualitatively using histomorphometrical methods
      in a rabbit model. The examined materials were autogenous bone, PRP alone, a
      mixture of autogenous bone and PRP, and whole blood (as a control). These
      materials were implanted into artificial defects prepared in rabbit tibiae. The
      observation period was set at 1, 2, 3, and 4 weeks. All specimens were used for
      histologic evaluation and 2- and 4-week specimens were used for
      histomorphometrical evaluations. The bone quantity increased when autogenous bone
      was applied but the percentage of mature bone in the autogenous bone site was
      smaller than in the PRP applied site. The results of this study suggested that
      the quantity of newly formed bone increased when autogenous bone was applied, but
      not when PRP only was applied. However, PRP might accelerate bone maturation by
      activating bone remodeling. According to this study, the bone quality could be
      altered by the application of PRP.

PMID- 15856778
TI  - [Socket healing after rat mandibular incisor extraction].
AB  - Prosthodontic treatment is difficult if the alveolar ridge is low or thin. To
      develop a method for alveolar ridge preservation after tooth extraction, we need
      an experimental model of a small animal, in which we can analyze the socket
      healing easily and quantitatively. The purpose of the present study was to
      establish such an experimental model. Ten weeks old male rats of Wistar strain
      were used. The edge of the right mandibular incisor was cut every three days
      three times and the incisor was extracted at three days after the final cut. The
      animals were sacrificed 0, 1, 2, 4, 8, 12 weeks after the extraction and the
      mandibles were dissected out. The length of the alveolar bone was measured on
      soft X-ray photographs and bone mineral content was measured with a dual energy X
      ray absorptiometer (DEXA). Then, transverse sections of the alveolar bone were
      prepared. Periodic three-times cutting of the edge of the mandibular incisor made
      the extraction easy. Quantitative analyses of new bone formation in the socket
      and the resorption of the alveolar bone were possible with soft X-ray photography
      and DEXA. The histological findings corresponded well with the data from the soft
      X-ray photos and DEXA measurements. The present results demonstrated the
      possibility of simple and quantitative analyses of socket healing after the
      extraction of rat mandibular incisors. This experimental model would be useful
      for developing a method to prevent atrophy of the alveolar ridge after tooth
      extraction.

PMID- 15856779
TI  - [The effect of "Oral Wet" for elderly people with xerostomia--the effect of oral
      rinse containing hialuronan].
AB  - Japanese society is aging rapidly, and the number of elderly people is
      increasing, hence the number of elderly people who have some diseases or
      disorders is growing. Therefore, Japanese dentists have to cope with various oral
      symptoms along with aging. Xerostomia is one of the most common symptoms of the
      elderly, but there is no established treatment. We tried to use an oral rinse
      "Oral Wet" that contains hialuronan and xylitol for elderly nursing home
      residents and examined the effect for Xerostomia. The usage of Oral Wet improved
      hyposalivation and unpleasant oral complaints of the elderly.

PMID- 15856780
TI  - Biomimetic measurement of allelochemical dynamics in the rhizosphere.
AB  - Polydimethylsiloxane (PDMS) materials were used to quantify levels of the
      photosynthesis inhibitor sorgoleone in the undisturbed rhizosphere of sorghum
      plants. The materials used included stir bars coated with PDMS (stir bar sorptive
      extraction), technical grade optical fiber coated with a thin film of PDMS
      (matrix-solid phase microextraction), and PDMS tubing. PDMS tubing retained the
      most sorgoleone. As analyzed by high performance liquid chromatography, amounts
      of sorgoleone retained on the PDMS materials increased with time. Other materials
      tested (polyurethane foam plugs, C18 and Tenax disks, and resin capsules) proved
      less suitable, as they were subject to sometimes extensive penetration by fine
      root hairs. These results demonstrate the potential for PDMS-based materials to
      monitor the release of allelochemicals in the undisturbed rhizosphere of
      allelopathic plants. Unlike extraction procedures that recover all available
      compounds present in the soil, PDMS functions in a manner more analogous to plant
      roots in sorbing compounds from soil solution or root exudates. Information on
      chemical dynamics in the rhizosphere is crucial for evaluating specific
      hypotheses of allelopathic effects, understanding allelopathic mechanisms, and
      assessing the importance of allelopathic processes in plant communities.

PMID- 15856781
TI  - Involvement of reactive oxygen species generated from melanin synthesis pathway
      in phytotoxicty of L-DOPA.
AB  - L-DOPA is an active allelochemical that inhibits plant growth. To determine
      whether the phytotoxicity is due to the reactive oxygen species generated during
      its oxidation to melanin, oxidative damage, melanin accumulation, and the effect
      of antioxidants on its phytotoxicity were examined in L-DOPA-tolerant (barnyard
      grass) and -susceptible (lettuce) plants, and in suspension-cultured carrot
      cells. L-DOPA suppressed root elongation in lettuce compared to barnyard grass.
      Levels of melanin and thiobarbituric acid reactive substances (TBARS) increased
      remarkably in L-DOPA-treated lettuce roots, but not in barnyard grass. L-DOPA
      also suppressed carrot cell growth to 60% of the control at 1 mM. Melanin content
      in 1 mM L-DOPA-treated carrot cells increased continuously; however, ascorbic
      acid and alpha-tocopherol suppressed accumulation. When melanin formation was
      inhibited by ascorbic acid and alpha-tocopherol, growth of L-DOPA-treated cells
      was restored. TBARS levels were higher in 1 mM L-DOPA-treated carrot cells than
      in untreated control cells 2 d after treatment, but not at 4 or 6 d. Ascorbic
      acid and alpha-tocopherol suppressed the production of lipid peroxide during the
      initial 2 d. These results suggest that the phytotoxicity of L-DOPA is due to
      oxidative stress caused by reactive oxygen species from the melanin synthesis
      pathway.

PMID- 15856782
TI  - Isolation and characterization of allelopathic volatiles from mugwort (Artemisia
      vulgaris).
AB  - Several volatile allelochemicals were identified and characterized from fresh
      leaf tissue of three distinct populations of the invasive perennial weed, mugwort
      (Artemisia vulgaris). A unique bioassay was used to demonstrate the release of
      volatile allelochemicals from leaf tissues. Leaf volatiles were trapped and
      analyzed via gas chromatography coupled with mass spectrometry. Some of the
      components identified were terpenes, including camphor, eucalyptol, alpha-pinene,
      and beta-pinene. Those commercially available were tested individually to
      determine their phytotoxicity. Concentrations of detectable volatiles differed in
      both absolute and relative proportions among the mugwort populations. The three
      mugwort populations consisted of a taller, highly branched population (ITH-1); a
      shorter, lesser-branched population (ITH-2) (both grown from rhizome fragments
      from managed landscapes); and a population grown from seed with lobed leaves
      (VT). Considerable interspecific variation existed in leaf morphology and leaf
      surface chemistry. Bioassays revealed that none of the individual monoterpenes
      could account for the observed phytotoxicity imparted by total leaf volatiles,
      suggesting a synergistic effect or activity of a component not tested. Despite
      inability to detect a single dominant phytotoxic compound, decreases in total
      terpene concentration with increase in leaf age correlated with decreases in
      phytotoxicity. The presence of bioactive terpenoids in leaf surface chemistry of
      younger mugwort tissue suggests a potential role for terpenoids in mugwort
      establishment and proliferation in introduced habitats.

PMID- 15856783
TI  - Effects of elevated CO2 on foliar quality and herbivore damage in a scrub oak
      ecosystem.
AB  - Atmospheric CO2 concentrations have increased exponentially over the last century
      and continuing increases are expected to have significant effects on ecosystems.
      We investigated the interactions among atmospheric CO2, foliar quality, and
      herbivory within a scrub oak community at the Kennedy Space Center, Florida.
      Sixteen plots of open-top chambers were followed; eight of which were exposed to
      ambient levels of CO2 (350 ppm), and eight of which were exposed to elevated
      levels of CO2 (700 ppm). We focused on three oak species, Quercus geminata,
      Quercus myrtifolia, Quercus chapmanii, and one nitrogen fixing legume, Galactia
      elliottii. There were declines in overall nitrogen and increases in C:N ratios
      under elevated CO2. Total carbon, phenolics (condensed tannins, hydrolyzable
      tannins, total phenolics) and fiber (cellulose, hemicellulose, lignin) did not
      change under elevated CO2 across plant species. Plant species differed in their
      relative foliar chemistries over time, however, the only consistent differences
      were higher nitrogen concentrations and lower C:N ratios in the nitrogen fixer
      when compared to the oak species. Under elevated CO2, damage by herbivores
      decreased for four of the six insect groups investigated. The overall declines in
      both foliar quality and herbivory under elevated CO2 treatments suggest that
      damage to plants may decline as atmospheric CO2 levels continue to rise.

PMID- 15856784
TI  - Effects of quantitative variation in allelochemicals in Plantago lanceolata on
      development of a generalist and a specialist herbivore and their endoparasitoids.
AB  - Studies in crop species show that the effect of plant allelochemicals is not
      necessarily restricted to herbivores, but can extend to (positive as well as
      negative) effects on performance at higher trophic levels, including the
      predators and parasitoids of herbivores. We examined how quantitative variation
      in allelochemicals (iridoid glycosides) in ribwort plantain, Plantago lanceolata,
      affects the development of a specialist and a generalist herbivore and their
      respective specialist and generalist endoparasitoids. Plants were grown from two
      selection lines that differed ca. 5-fold in the concentration of leaf iridoid
      glycosides. Development time of the specialist herbivore, Melitaea cinxia, and
      its solitary endoparasitoid, Hyposoter horticola, proceeded most rapidly when
      reared on the high iridoid line, whereas pupal mass in M. cinxia and adult mass
      in H. horticola were unaffected by plant line. Cotesia melitaearum, a gregarious
      endoparasitoid of M. cinxia, performed equally well on hosts feeding on the two
      lines of P. lanceolata. In contrast, the pupal mass of the generalist herbivore,
      Spodoptera exigua, and the emerging adult mass of its solitary endoparasitoid, C.
      marginiventris, were significantly lower when reared on the high line, whereas
      development time was unaffected. The results are discussed with regards to (1)
      differences between specialist and generalist herbivores and their natural
      enemies to quantitative variation in plant secondary chemistry, and (2)
      potentially differing selection pressures on plant defense.

PMID- 15856785
TI  - Effect of volatile constituents from Securidaca longepedunculata on insect pests
      of stored grain.
AB  - Securidaca longepedunculata Fers (Polygalaceae) is commonly used as a traditional
      medicine in many parts of Africa as well as against a number of invertebrate
      pests, including insects infesting stored grain. The present study showed that S.
      longepedunculata root powder, its methanol extract, and the main volatile
      component, methyl salicylate, exhibit repellent and toxic properties to
      Sitophilus zeamais adults. Adult S. zeamais that were given a choice between
      untreated maize and maize treated with root powder, extract, or synthetic methyl
      salicylate in a four-way choice olfactometer significantly preferred the control
      maize. Methyl salicylate vapor also had a dose-dependant fumigant effect against
      S. zeamais, Rhyzopertha dominica, and Prostephanus truncates, with a LD100
      achieved with a 60microl dose in a 1-l container against all three insect species
      after 24 hr of exposure. Probit analyses estimated LD50 values between 34 and 36
      microl (95% CI) for all insect species. Furthermore, prolonged exposure for 6
      days showed that lower amounts (30 microl) of methyl salicylate vapor were able
      to induce 100% adult mortality of the three insect species. The implications are
      discussed in the context of improving stored product pest control by small-scale
      subsistence farmers in Africa.

PMID- 15856786
TI  - Kinetics of the natural evolution of hydrogen cyanide in plants in neotropical
      Pteridium arachnoideum and its ecological significance.
AB  - The time-dependent natural release of hydrogen cyanide (HCN) was studied
      quantitatively using young croziers of the neotropical bracken fern Pteridium
      arachnoideum. HCN production was quantified in crushed tissue using a flow
      reactor at 30.0 +/- 0.1 degrees C. Released HCN was carried into appropriate
      traps with a moist air flow. Aliquots were drawn from the traps at fixed time
      intervals, and the HCN concentration was evaluated spectroscopically. All
      available prunasin (Pru), the only cyanogenic glycoside present, underwent
      decomposition into HCN in less than 1200 min. Fiddleheads (N = 76) contained 1.84
      107.70 mg Pru g(1) dw in a continuous fashion suggesting genetic polymorphism.
      Acyanogenic morphs were rare (1/77). From the kinetics of the samples with Pru
      content near the median histographic distribution (N = 46), accumulated HCN
      formation as a function of time, initial velocities, average HCN production rate,
      and corresponding rate equations were obtained. Initial and average velocities
      correlated well with total Pru content. The yield of cyanide liberation varied
      widely between 0.51 and 47.86 microg HCN min(-1) g(-1) dw and was a linear
      function of [Pru]t. However, the beta-glucosidase enzyme involved in this
      reaction was not rate limiting and occurs in excess in the natural system. Enzyme
      activity was found to be independent of [Pru]t. The contribution of HCN as an
      allomone-upon-request against herbivores was assessed quantitatively. Bracken
      fiddleheads produced a pulse of HCN soon after tissue injury that waned rapidly,
      leaving a large portion of intact prunasin to decompose more slowly in the
      herbivore's lumen. The balance between the external and internal courses was
      found to depend on the concentration of prunasin in the plant, the amount of
      crozier eaten, and the time used to consume it.

PMID- 15856787
TI  - Influence of diet-related chemical cues from predators on the hatching of egg
      carrying spiders.
AB  - Previous studies have shown that animals may make adaptive adjustments in
      response to chemical cues from predators, but hatching responses to diet-related
      chemical cues from predators have not been previously demonstrated. In the system
      studied here, the predator is an araneophagic jumping spider (Salticidae), Portia
      labiata, and the prey organism is a subsocial spitting spider, Scytodes pallida
      (Scytodidae). The spitting spider carries its eggs in its chelicerae, and
      carrying eggs is known to make it more vulnerable to predators. It is also known
      from an earlier study that the prior diet of the predator alters how dangerous
      the individual predator is to the spitting spider. In the experiments reported
      here, incubation time was shorter when volatile cues from the predator were
      present and longer in control tests when no chemical cues from the predator were
      present. The previous predator's diet also influenced incubation time: when in
      the presence of volatile cues from individuals of P. labiata that had previously
      fed on individuals of S. pallida, incubation time was shorter than when in the
      presence of volatile cues from individuals of P. labiata that had been feeding
      instead on house flies.

PMID- 15856788
TI  - Parallel arms races between garter snakes and newts involving tetrodotoxin as the
      phenotypic interface of coevolution.
AB  - Parallel "arms races" involving the same or similar phenotypic interfaces allow
      inference about selective forces driving coevolution, as well as the importance
      of phylogenetic and phenotypic constraints in coevolution. Here, we report the
      existence of apparent parallel arms races between species pairs of garter snakes
      and their toxic newt prey that indicate independent evolutionary origins of a key
      phenotype in the interface. In at least one area of sympatry, the aquatic garter
      snake, Thamnophis couchii, has evolved elevated resistance to the neurotoxin
      tetrodotoxin (TTX), present in the newt Taricha torosa. Previous studies have
      shown that a distantly related garter snake, Thamnophis sirtalis, has coevolved
      with another newt species that possesses TTX, Taricha granulosa. Patterns of
      within population variation and phenotypic tradeoffs between TTX resistance and
      sprint speed suggest that the mechanism of resistance is similar in both species
      of snake, yet phylogenetic evidence indicates the independent origins of elevated
      resistance to TTX.

PMID- 15856789
TI  - Inheritance of resistance to mammalian herbivores and of plant defensive
      chemistry in an Eucalyptus species.
AB  - Hybridization in plants provides an opportunity to investigate the patterns of
      inheritance of hybrid resistance to herbivores, and of the plant mechanisms
      conferring this resistance such as plant secondary metabolites. We investigated
      how inter-race differences in resistance of Eucalyptus globulus to a generalist
      mammalian herbivore, Trichosurus vulpecula, are inherited in their Fl hybrids. We
      assessed browsing damage of 3-year-old trees in a common environment field trial
      on four hybrid types of known progeny. The progeny were artificial intra-race
      crosses and reciprocal inter-race F1 hybrids of two geographically distinct
      populations (races) of E. globulus north-eastern Tasmania and south-eastern
      Tasmania. Populations of trees from north-eastern Tasmania are relatively
      susceptible to browsing by T. vulpecula, while populations from south-eastern
      Tasmania are more resistant. We assessed the preferences of these trees in a
      series of paired feeding trials with captive animals to test the field trial
      results and also investigated the patterns of inheritance of plant secondary
      metabolites. Our results demonstrated that the phenotypic expression of
      resistance of the inter-race Fl hybrids supported the additive pattern of
      inheritance, as these hybrids were intermediate in resistance compared to the
      pure parental hybrids. The expression of plant secondary metabolites in the Fl
      hybrids varied among major groups of individual compounds. The most common
      pattern supported was dominance towards one of the parental types. Together,
      condensed tannins and essential oils appeared to explain the observed patterns of
      resistance among the four hybrid types. While both chemical groups were inherited
      in a dominant manner in the inter-race Fl hybrids, the direction of dominance was
      opposite. Their combined concentration, however, was inherited in an additive
      manner, consistent with the phenotypic differences in browsing.

PMID- 15856790
TI  - Stir bar sorptive extraction: a new quantitative and comprehensive sampling
      technique for determination of chemical signal profiles from biological media.
AB  - Various applications of a novel sampling procedure in chemical ecology are
      outlined. The stir bar extraction method features the analytical reproducibility
      needed in recording the analytical profiles of volatile and semivolatile
      components of biological mixtures. This methodology has been demonstrated here
      through the examples of small volume urine samples, glandular tissue volatiles,
      and the air blown through animal cages. Its analytical merits are compared with
      those of the previously established purge-and-trap (dynamic headspace) technique.

PMID- 15856791
TI  - Optimization of pheromone lure and trap characteristics for currant clearwing,
      Synanthedon tipuliformis.
AB  - Currant clearwing Synanthedon tipuliformis (Sesiidae) has been a pioneering and
      successful target of mating disruption in New Zealand, with virtually universal
      black currant industry adoption since c. 1990. Recent unexplained control
      failures using mating disruption lead to questions about pheromone efficacy. In
      this study, we have investigated the possible reasons for reduced control from
      mating disruption, and report improvements in trap catch based on pheromone
      loading and trap color. No differences were found in electrophysiological
      responses to pheromone components from two New Zealand populations. Male moth
      catches in traps baited with synthetic lures were disrupted in the presence of
      mating disruption dispensers ( > 99.99%) indicating no apparent barrier to
      efficacy from the pheromone formulation. Field behavioral observations confirmed
      this result. Male attraction to yellow delta traps was equivalent to green delta
      traps, but was greater than to red, black, blue, or white traps. Solid yellow
      delta traps were more attractive than black traps with yellow stripes, the latter
      designed to mimic the color pattern of the insect. Solid yellow funnel traps were
      less attractive than a composite of green, yellow, and white funnel traps. Trap
      catch increased as a function of pheromone loading, and trap color. In another
      experiment conducted in Tasmania, there was no difference in catch with single
      component [(E,Z)-2,13-octadecadienyl acetate] or two component lures [97% (E,Z)
      2,13-octadecadienyl acetate:3% (E,Z)-3,13octadecadienyl acetate], refuting the
      suggestion of a different pheromone strain there.

PMID- 15856792
TI  - 6-alkylsalicylic acids and 6-alkylresorcylic acids from ants in the genus
      Crematogaster from Brunei.
AB  - The defensive chemistry of two species of ants from Brunei in the genus
      Crematogaster (Physocrema group) has been investigated. Ants in this group
      release a white secretion from hypertrophied metapleural glands on their thorax
      when they are disturbed. Previously, one species in this group has been shown to
      produce alkylphenols and alkylresorcinols. In the present investigation, similar
      compounds along with salicylic acids and resorcylic acids that are anacardic acid
      and olivetolic acid homologs, respectively, are described from two species. The
      structures of these compounds were suggested by their spectroscopic data and
      confirmed by direct comparison with synthetic samples. Some of these compounds
      occur in lichens and have well documented physiological activities.

PMID- 15856793
TI  - Volatile exudates from the oribatid mite, Platynothrus peltifer.
AB  - Gas chromatographic-mass spectrometric analysis of whole body extracts of
      Platynothrus peltifer, a desmonomatan oribatid mite that belongs to the family
      Camisiidae, exhibited a basic profile of seven compounds, comprising the
      monoterpenes neral, geranial, and nerylformate; the aromatics 3-hydroxybenzene
      1,2-dicarbaldehyde (= gamma-acaridial) and 2-formyl-3-hydroxybenzyl formate (=
      rhizoglyphinyl formate), and two unsaturated Cl7-hydrocarbons, 6,9-heptadecadiene
      and 8-heptadecene. Neryl formate, gamma-acaridial, and rhizoglyphinyl formate
      were the main components and amounted to 80% of the extracts. With the exception
      of y-acaridial (relative abundance varied considerably among samples), this
      chemical profile was consistently present in extracts of P. peltifer from nine
      different localities in SE-Austria. In addition, two further components, 2,3
      dihydroxy benzaldehyde and 7-hydroxyphthalide, both probably of non-oil gland
      origin, infrequently were detected in the extracts. The aromatic compound
      rhizoglyphinyl formate, also known from Astigmata, was found for the first time
      in extracts of Oribatida, whereas all other compounds have already been reported
      from other oribatid species. The hydrocarbons are generally considered to
      represent plesiomorphic characters of mite oil gland secretions, whereas the
      monoterpenes and y-acaridial form a part of the so-called "astigmatid compounds"
      that are thought to be characteristic for middlederivative Mixonomata and all
      more highly derived oribatid groups (including Astigmata).

PMID- 15856794
TI  - Quantification of invertase activity in ants under field conditions.
AB  - Invertases (EC 3.2.1.26) are hydrolases that cleave sucrose into the
      monosacccharides, glucose, and fructose. They play a central role in carbohydrate
      metabolism of plants and animals. Methods presented so far to quantify invertase
      activity in ants or other animals have been hampered by the variability in both
      substrates and products of the enzymatic reaction in animals whose carbohydrate
      metabolism is highly active. Our method is based on a spectrophotometric
      quantification of the kinetics of glucose release. We first obtained an
      equilibrium state summarizing reactions of any carbohydrates and enzymes that are
      present in the extract. Sucrose was then added to quantify invertase activity as
      newly released glucose. Invertase activities differed significantly among species
      of ants. Variances were lowest among individuals from the same colony and highest
      among different species. When preparations were made from ants of the same
      species, invertase activity was linearly related to the number of ants used for
      extraction. Our method does not require ants to be kept on specific substrates
      prior to the experiment, or expensive or large equipment. It, thus, appears
      suitable for dealing with a broad range of physiological, ecological, and
      evolutionary questions.

PMID- 15856795
TI  - States target remaining impediments to HSA success.

PMID- 15856796
TI  - NIH opens access to research.

PMID- 15856797
TI  - The future of genomics: hope or hype?

PMID- 15856798
TI  - Transforming health care at the CORE.

PMID- 15856799
TI  - Raising the bar for complementary and alternative medicine.

PMID- 15856800
TI  - Preserving your purest treasure: managing corporate reputation.

PMID- 15856801
TI  - Obesity: health insurance plans respond to a public health challenge.

PMID- 15856802
TI  - Weigh the risks before limiting coverage.

PMID- 15856803
TI  - The future of Medicare supplement products ... or is there one?

PMID- 15856805
TI  - Health plans offer innovative care for Medicaid members.

PMID- 15856804
TI  - Dental carriers use cyberspace to provide superior service.

PMID- 15856806
TI  - Business process automation: closing the automation gap.

PMID- 15856807
TI  - Percutaneous vertebroplasty: an update.
AB  - Percutaneous vertebroplasty is an imaging-guided interventional technique in
      which surgical polymethylmethacrylate is injected via a large bore needle into a
      painful compressed vertebral body. This technique is safe and effective, and
      provides increased strength and pain relief in vertebrae weakened by bone
      diseases. Among the current indications for vertebroplasty are intractable
      nonradicular pain caused by compression fractures due to osteoporosis, myeloma,
      metastasis, and aggressive vertebral hemangioma. Contraindications include
      bleeding disorder, unstable fracture, and lack of definable vertebral collapse.
      The preprocedural evaluation, technique, complications, and expected results of
      performing this procedure are also reviewed.

PMID- 15856808
TI  - Complications of percutaneous vertebroplasty and their prevention.
AB  - Vertebroplasty is an efficient treatment of vertebral collapses of malignant or
      benign origin but also carries a risk of complications. Cement extravasation is a
      frequent occurrence in vertebroplasty. It is well tolerated in the large majority
      of cases but is also the main source of complications especially nerve root
      compression in case of cement leakage into the intervertebral foramen and
      pulmonary embolism of cement complicating venous cement leakage. Rate of these
      complications are much higher in malignant than in osteoporotic collapses. The
      risk of neurological complication also increases at the cervical level. In
      addition, incidence of new vertebral fractures in adjacent vertebrae may be
      increased by vertebroplasty. General reactions possibly due to a reflex reaction
      to intramedullary bone injection and fat embolism may also occur. This article
      reviews the safety measures to reduce the risk of cement extravasation including
      high quality permanent radiological guidance enabling early detection of cement
      extravasation, use of conscious sedation, bilateral transpedicular approach at
      the thoracic and lumbar levels, careful selection of the bone penetration site in
      order to make a single vertebral needle path, careful needle placement to avoid
      the risk of cortical breakthrough, use of a well-opacified and refrigerated
      cement with a toothpaste consistency.

PMID- 15856809
TI  - Lumbar discography: current concepts and controversies.
AB  - Lumbar provocation discography is an invasive diagnostic procedure to identify
      pain originating from within the lumbar discs. Specific morphological changes
      within the disc, classified as radial fissures, can be imaged following the
      injection of radiopaque contrast into the nucleus pulposus. The reproduction of
      concordant low back and/or referred somatic pain to the lower extremity under
      controlled conditions and the demonstration of annular radial tears are part of a
      spectrum of internal disc disruption that is separate from disc degeneration. A
      review of the validity and technique of lumbar discography as well as recently
      described causes of false positive responses are presented.

PMID- 15856810
TI  - Radiofrequency and laser ablation of spinal lesions.
AB  - Radiofrequency current and laser energy can be delivered locally through
      electrode-needle or optical fiber inserted in the tissue and allows local
      ablation of tissues, up to a volume of 4 to 5 cm in diameter with one application
      or vaporizes tissue. Tumor ablation guided with medical imaging proved a high
      local efficacy over 90% for tumors less than 25 mm in the liver, lung, and
      kidney. The spinal applications of the thermal energy of RF and laser are
      reported in this paper. First, the tumor ablation is reviewed with malignant and
      benign tumors. In malignant tumors, radiofrequency is very efficient in local
      tumor control and in pain management. The second part of this paper is devoted to
      disk diseases where laser and RF techniques increase their applications. The
      technique, indications and results of these techniques are reported and
      illustrated.

PMID- 15856811
TI  - Facet, nerve root, and epidural block.
AB  - Percutaneous spinal blocks are diagnostic or therapeutic procedures designed to
      help the neurologist or orthopaedist in their evaluation of confounding low back
      and/or lower extremity pain. During the initial workup, nonspinal percutaneous
      blocks, such as hip or sacroiliac joint injection, may be necessary to exclude
      one of these sites as the origin of the patient's symptoms. Generally, these
      blocks are safe, quick and easily performed under fluoroscopic guidance. Once the
      appropriate needle position has been obtained and the short-and/or long-acting
      anaesthetics instilled into the appropriate site, the patient's response to the
      block should be documented and transmitted to their referring physician. In the
      case that the block is successful, the block may be repeated at intervals for
      pain control, particularly in patients who chose not to have surgery or who are
      poor surgical candidates. Ultimately, however, as the patient's arthritis and/or
      disc degeneration progresses, the blocks will become less and less effective and
      a more permanent solution will be required. This chapter explains the
      indications, injection options, and methods of performing these various spinal
      blocks.

PMID- 15856812
TI  - Advances in spinal fusion.
AB  - Since its initial description about a century ago, spinal fusion has become a
      common surgical intervention in the treatment of various debilitating spinal
      disorders. However, given the complexities and demands of the procedure, patient
      selection remains a key component in the success of the operation. In this
      article, we will review the various indications for spinal fusion, the current
      advances in fusion techniques, as well as the potential complications associated
      with the procedure.

PMID- 15856813
TI  - Blessings from above. Large Catholic healthcare systems have seen their revenue,
      profits rebound. How will that affect spending on charity care?
AB  - The U.S. Catholic healthcare system is healthy financially, but providers are
      warily expecting cuts in federal reimbursement. Large systems have worked to
      become more efficient and profitable, and those efforts are paying off. "We are
      doing well. We've continued to improve our operating margins," says Kris Zimmer,
      left, an executive at SSM Health Care.

PMID- 15856814
TI  - New pope, old directives.

PMID- 15856815
TI  - Career shifts? Plan to cut reimbursements gets docs to thinking.

PMID- 15856816
TI  - Medicare hot spot. Miami-Dade docs act as insurance providers.

PMID- 15856817
TI  - Calif. ordered to close 1, open 1.

PMID- 15856818
TI  - Preparing for disaster. Conn., N.J. ERs participate in bioterror drill.

PMID- 15856819
TI  - Spanning the globe. UPMC proposes partnerships in Ireland, Las Vegas.

PMID- 15856820
TI  - Minnesota thaw, Fairview tells state it will ease collection practices.

PMID- 15856821
TI  - Calif. ruling limits liens.

PMID- 15856822
TI  - And the winners are ... CEO IT Achievement Award recipients announced.

PMID- 15856823
TI  - Quality. Accepting the inevitable.

PMID- 15856824
TI  - Ind. system has JCAHO trouble.

PMID- 15856825
TI  - A reimbursement conundrum.

PMID- 15856826
TI  - Another nursing shortage. More nurses are adding financial management expertise
      and rising to executive positions-just don't look for too many of them in the
      CFO's office.

PMID- 15856827
TI  - Transporting trouble. Ambulance contracts give Fla. system a rough ride.

PMID- 15856828
TI  - [Peripheral, central and psychic deafness: diagnosis difficulties in case of
      autism child].
AB  - The population ofchildren seen in the Georges Vacola day hospital, opened 20
      years, suffer from serious personality disorders and from, hearing deficit.
      Speech and language disorders were present in every case. However. autism seems
      to be less prominent. The dtlfficulties in communicate are associated with
      problems of memory comprehension and hearing deficit. Many of the autistic
      children have associated deafness. The importance of central and functional
      deafness is highlighted. Deficits of mechanisms indispensable to the recognition,
      discrimination, structuralization, memorization of auditory stimuli are
      discussed. Another study including 500 autistic children showed that 15% of these
      children aged 11 to 13 years presented with auditory disorders.

PMID- 15856829
TI  - [Central auditory processing assessment].
AB  - OBJECTIVE: A battery of tests for central auditory processing assessment has been
      designed in French. This battery, BAC for Bilan Auditif Central (central auditory
      processing), consists of'fbur tyvpes of tests: A speech-in-noise test, a dichotic
      test, a temporal processing test and a binaural interaction test. MATERIAL AND
      METHOD: Descriptive statistics were computed on data obtained from 668 subjects
      ranging from 5 to 85 years old. RESULTS: Tests scores of the speech-in-noise
      test, the dichotic test and the binaural interaction test showed a normal
      distribution. Test scores of the temporal processing demonstrates a ceiling
      effect. Effcts of maturation and involution were clearly visible for all tests.
      CONCLUSION: The low correlation between scores obtained from the four tests
      pointed to the need for a battery ofseveral tests to assess central auditory
      processing.

PMID- 15856830
TI  - [Study of the supra-glottic pressure during partial constriction of the vocal
      tract].
AB  - OBJECTIVES: Phonation in a small plastic tube 22 cm length and 5 mms diameter
      (basic exercise of the method of Dr Amy de la Breteque), is current practice in
      vocal rehabilitation in France. This work aims to show the effects of this method
      on the glottic vibration. The hypothesis was that at the time of phonation in the
      tube with a strong flow as recommended in the method, the vocal cords vibrate
      without contact. This limits the mechanical trauma at this level. MATERIAL AND
      METHODS: We have analyzed the sound production in a tube in 11 trained and not
      trained subjects. We simultaneously collected the intra-oral air pressure and the
      vocal signal which was subjected to a spectral analysis. RESULTS: Spectral
      analysis confirmed that the signal was produced correctly i.e. with a strong flow
      and without interruption of the sound less rich in harmonics. We interpreted
      these results in the light of our preceding works on the glottic vibration and we
      show that this vocal production was of the sinusoidal type; this implies the
      absence of physical contact between the vocal cords, which validates our
      hypothesis. CONCLUSION: Further works are necessary to better understand the
      physical relations between the supra-glottic aerodynamic phenomena and the
      vibratory functioning of the vocal cords and also to analyze the therapeutic
      potential ofthe method within speech therapy rehabilitation.

PMID- 15856831
TI  - [Stuttering and Tourette's syndrome: a short tutorial and account of a four years
      experience in a stuttering clinic constriction of the vocal tract].
AB  - The author presents a short tutorial of Gilles de la Tourette's syndrome followed
      by a state of the art of review of the clinical links between stuttering and the
      different kinds of Tourette and tics disorders. The author relates her own
      experience of working for four consecutive years at the new stuttering diagnostic
      center at the "Hopital Europeen Georges Pompidou ". The article ends with a
      practical review of the actual therapies available when such a diagnosis is made.

PMID- 15856832
TI  - [Different clinical approaches: clinical reports].
AB  - The three reported clinical cases discussed clearly show that patients may often
      benefit from clinical pathways beyond the usual paradigms. Less known therapeutic
      options may avoid surgical intervention or seriously protracted rehabilitation
      programs if the patient can be made to accept the suggested acoustic and
      functional changes as every day habits. Different clinical approaches, associated
      with personal expressive development, can sometimes foster favorable therapeutic
      growth and avoid recourse to surgical intervention.

PMID- 15856833
TI  - [The Voice Handicap Index: impact of the translation in French on the
      validation].
AB  - The aim of this prospective investigation was to validate a French version of the
      Voice Handicap Index (VHI). A population of 52 normal subjects and 63 patients
      with voice disorders replied to the questionnaire at the day of their first
      consultation and ten to thirty days after the consultation (before any
      treatment). Reproducing the methodology of the American authors, the test-retest
      reliability and the internal consistency reliability were measured. The validity
      and the sensibility related to a non dysphonic population were also analysed.
      Regarding the normal subjects, the maximum scores for total score and subscale
      scores were 20 (total), 12 (physical), 7 (functional), 6 (Emotional). These
      scores are statistically different when compared with pathological subjects (p <
      0.00001). Test-Retest stability of the pathological subjects was found to be
      satisfactory for both total score and subscale scores (r > 0.87). From this data
      set, the critical difference scores were derived for the VHI total score (15
      points), for the physical subscale (9 points) and for the functional and
      emotional.subscales (6 points each). As for as the internal consistency
      reliability, Cronbach's alpha is correct (r > 7) for the pathological subjects.
      Yet, the analysis of the validity reply by reply, reveals some abnormalities. In
      conclusion, the validity of the French translation of the VHI is confirmed but
      the results prompt us to improve the quality of the translation.

PMID- 15856834
TI  - [Voice handicap evaluation after supracricoid partial laryngectomy].
AB  - The importance of patient self-impressions has been emphasized in determining the
      success of cancer treatment. The supracricoid partial laryngectomy (SCPL) is
      recognized as a suitable procedure for the treatment of T1b and T2 glottic
      carcinoma. The aim of this surgical procedure is the preservation of a
      physiologic phonation with optimal oncologic control. METHOD: Measurements
      included Voice handicap Index (VHI), Voice Related Quality of'Life (VRQL),
      subjective (GRBAS) and objective analysis. OBJECTIVES: evaluate voice problems
      after SCPL, provide correlations between patients' daily activities, VHI, and
      subjective evaluation of the dysphonia. PATIENTS: 53 patients were assessed more
      than 1 year after SCPL. 26 patients, less than 60 years of age and professionally
      active were included. The mean age was 48 years (43 to 59 years). Eleven patients
      had professional activities in the communications industry requiring a compulsory
      daily use of their voices. RESULTS: 57.6% of the active patients underwent a
      cessation or an adaptation of their professional activities. The mean VHI was
      52.22. It was respectively 36.3, 50.03 and 52.42 according to the grade 1, 2, 3
      of dysphonia. Correlations between VHI and the time laps since intervention (p:
      0.047). discontinuation of professional activities (p: 0.037), and grade of
      dysphonia (p: 0.049) were found. CONCLUSION: VHI allows an evaluation of the
      voice problems after SCPL. A significant impact on voice is reported after SCPL
      and may influence the patient's life, with potential disturbance of their
      professional activities. Potential post surgical voice impact must be considered
      when the therapeutic options are discussed.

PMID- 15856835
TI  - [Voice after supracricoid partial laryngectomy: comparison of two phonatory
      mechanisms].
AB  - INTRODUCTION: Different laryngeal phonatory mechanisms may be observed at long
      term after supracricoid laryngectomy. For this study two mechanisms are
      differentiated. The "dilated" mechanism is the consequence of a forward movement
      of the neolarynx creating a new resonance cavity. The "contracted" mechanism
      tallies with the backward contraction of the base of the tongue and the
      contraction of the posterior pharyngeal wall compressing the neolarynx.
      OBJECTIVE: The aim of the study is to determine if the voice outcome is different
      between these two kinds of mechanisms. MATERIAL AND METHOD: The method is based
      on the selection of a homogeneous group: 12 patients operated by
      cricoepiglottopexy with a follow up superior to two years and with a stable voice
      and a full neoglottic closure during phonation. The voice quality and the
      phonatory mechanism are analysed. Regarding voice assessment, a self evaluation
      with the vocal handicap index adapted for the study and the GRBAS scale are
      carried-out. Frequency (usual, minimum, maximum, range) and loudness are used to
      appreciate the vocal capacities. The phonatory mechanism is studied by
      videolaryngostroboscopy, performed tongue free, with a normal /e/ and a high-low
      transition pitch. RESULTS: The outcomes point out a difference between the two
      mechanisms. The best vocal results are observed in the "dilated" mechanism for
      the studied parameters and mainly for the frequency parameters. CONCLUSION: The
      discovery of numerous phonatory mechanisms after supracricoid laryngectomy
      independent from neoglottic closure lead us to further studies of the impact of
      this type of surgery on articulatory patterns.

PMID- 15856836
TI  - [International Conference on Voice Physiology and Biomechanics, Marseille 2004].
AB  - The Fourth meeting of the International Conference on Voice Physiology and
      Biomechanics took place at Marseille last August 18-20, under the Presidence of
      Antoine Giovanni, Maurice Ouaknine and Philippe Dejonckere. 142 searchers and
      specialists of all the world to speak on physiology of the glottic vibration. A
      brief report on this conference.

PMID- 15856837
TI  - [Stuttering of the "Miror" of Andrei Tarkovski and "Passion" of Jean Luc Godard].
AB  - The "Miror" (1974) of Andrei Tarkovski and "Passion" (1982) of Jean-Luc Godard
      are two movies where the stuttering takes an important place. This trouble is a
      main subject of these two movies.

PMID- 15856838
TI  - [Stingy speakers].
AB  - While the greater part of the patients that we rehabilitate like to speak again
      in a carried and loud voice; some of them more or less clearly show their
      reluctance to "amplify" their voice and prefer keeping on with speaking in a
      conversational tone, even though this appears to be inappropriate in a
      professional context. Listening attentively to what they can say about it enables
      us to understand that their reluctance stems from the fact that they find their
      voice a particularly valuable possession. Hence their anxiety to save their
      voice, as if using it may also cause its exhaustion. Of course, with some appeal
      to their common sense and some persuasion, it is possible to convince the
      patients that carrying one's voice efficiently saves it as far as it makes use of
      the resonators. An argument that henceforth makes them accept to carry their
      voice. Nothing could be more justified than the satisfaction the rehabilitator
      can feel. Yet, is this satisfaction not felt to the detriment of the
      psychological organisation of the patient who also has to be regarded as a
      subject? A clinic example will allow us to raise the issue of a possible
      therapeutic failure and as a result to make an issue of the possibility for
      speech therapy to exist without any theoretical model of psychological
      functioning.

PMID- 15856839
TI  - After Code Green.

PMID- 15856840
TI  - Are we out of our minds with nursing stress?

PMID- 15856841
TI  - Beyond Code Green: The untold story about the Beth Israel and New England
      Deaconess Hospital merger. Interview by Marie Manthey.

PMID- 15856842
TI  - Code Green Revisted. Interview by Marie Manthey.

PMID- 15856843
TI  - [The multiple faces of sexuality].

PMID- 15856844
TI  - [Sex and brain].
AB  - Does the brain of a man or a woman develop and function in the same way? Recent
      research results tend to suggest that this is not the case. First, it appears
      that the level of expression of genes present on the sexual chromosomes could
      vary as a function of the gender in organs including in the brain. Second, sexual
      hormones, such as estrogens, were found to have important trophic effects on the
      development of synaptic networks as well as to influence many neuronal
      properties. Together, these two mechanisms have probably contributed to the
      selection through generations of functioning modes, sensitivities or behaviours
      that may differ between males and females.

PMID- 15856845
TI  - [Pharmacological treatment of female sexual disfunction: chimera or reality?].
AB  - Sexual dysfunction is defined as a disturbance in the sexual response cycle or as
      a pain with sexual intercourse. The prevalence of sexual dysfunctions is
      approximately 40% in the female population. The disorders affecting sexual desire
      are the most common sexual dysfunctions encountered in women. Whereas recent
      studies have demonstrated clear influences of hormones on sexual dysfunctions, no
      pharmacological treatment has been approved for that indication. We will review
      here several pharmacological treatment strategies proposed in case of sexual
      dysfunction, underlying the fact that they are effective only to treat specific
      cases of sexual disorders but cannot replace the sex therapies.

PMID- 15856846
TI  - [Why women consult sexologists: an approach for practicing physicians].
AB  - Female sexual dysfunctions are less known than male ones because women are more
      discrete and introverted. Female genitals are mostly internal and women live sex
      more cerebrally and sentimentally than men. Still half the patients my current
      sexological consultation are women. They seek help due for lack of desire,
      frigidity, coital or clitoridal anorgasmy, dyspareuny, vaginism and problems
      related to pregnancy or the post-partum period. This article describes how to
      construct a precise clinical etiology following a "5 circles" scheme, which will
      help to determine the most adequate therapeutic approach.

PMID- 15856847
TI  - [Eros and Psyche: everything you want to now about their discreet relationship].
AB  - For a follower of his liberating cause in the 20th century, it is a wholly
      technological destiny that now relegates medical sexology into treating the
      instrumental functions of Sexology. How is it possible to separate so radically
      the dancer from the dance? Hopefully the opportunity will arise again for
      physicians and sexologists to become builders of new psychological spaces. The
      author is suggesting a synthetic approach showing how sexuality is involved in
      life. The author even describes some heuristics he developed in the framework of
      a seminary guided by Professor Georges Abraham. Accordingly, the physician will
      be allowed to join the "dancers", or at least to find a path to the present
      realities leading further than codified perspectives of therapy.

PMID- 15856848
TI  - [The erotic imaginary in childhood].
AB  - Through four clinical vignettes we tried to demonstrate that the erotic imaginary
      in childhood couldn't be separated from some theoretical conception typical of
      this age. Only one of the cases we have described could be an exception, showing
      some eroticism without any special mental representation of it.

PMID- 15856849
TI  - [Sexuality and aging].

PMID- 15856850
TI  - [Preventing falls and fractures today].
AB  - The aim of preventive interventions is to reduce the number of falls and their
      traumatic consequences, especially hip fractures. A number of preventive
      interventional studies have shown that multifactorial, multidisciplinary
      interventions (improving mobility, reducing the use of psychotropic medications
      and environmental homes modifications) for community dwelling older people are
      effective. Improving strength and balance is key. Monofactorial interventions
      (education, home hazard modification) have not been shown to be effective.
      Supplementation with Vitamin D in association with calcium, in addition to its
      protective effect on fractures seems to reduce de number of falls by improving
      muscle strength. Taking into account this new information in everyday practice is
      of utmost importance.

PMID- 15856851
TI  - [Rapid prenatal diagnosis of chromosome abnormalities: from FISH to QF-PCR].
AB  - Prenatal diagnosis for pregnancies at increased risk for chromosome abnormalities
      is routinely undertaken by karyotype analysis. While karyotype analysis remains
      the standard method to detect structural and copy number changes of chromosomes,
      it requires prolonged cell culture resulting in average reporting times of about
      two weeks. To relieve parental anxiety, and improve the quality and plasticity of
      pregnancy management, rapid methods, such as FISH and QF-PCR have recently been
      developed. These procedures are capable of detecting > 70% of chromosome
      abnormalities, and deliver a reliable diagnosis within 24 hours. Here we compare
      and discuss the advantages and limits of these rapid assays, and position them
      into a broader ethical context.

PMID- 15856852
TI  - [Manifesto on "Health politics: stop the scuttling!": to (almost) conclude].

PMID- 15856853
TI  - [Will intrinsa see the light? (I)].

PMID- 15856854
TI  - [The Pope's cannula].

PMID- 15856855
TI  - [The super-resistant New-Yorker AIDS virus is not the one we think].

PMID- 15856856
TI  - [Premium increase for smokers].

PMID- 15856857
TI  - Acute renal failure associated with dysfunctioning detrusor muscle in multiple
      sclerosis.
AB  - Patients with multiple sclerosis (MS) typically have neurogenic lower urinary
      tract dysfunction. Most patients present with bladder hyperreflexia and failure
      to empty the bladder secondary to detrusor-distal sphincter dyssynergia. This
      case study is unique in the literature in reporting on a patient presenting with
      acute renal failure (ARF) due to vesico-sphincter dysfunction associated with MS.
      A 64-year-old man with MS presented in the emergency department with the chief
      complaint of a marked decrease in urinary output for 2 days and weakness. He had
      been treated for MS for 7 years. A mass compatible with a full bladder was
      palpated in the suprapubic region on examination. Digital rectal examination
      disclosed grade I-Il prostate hypertrophy. Urinary catheters were inserted and
      urinary output was monitored. The residual urine was drained and recorded as 1100
      mL. Initial laboratory findings, such as the BUN/creatinine ratio, urinary sodium
      concentration, and urine gravity, were compatible with ARF. The patient recovered
      rapidly in 24 hours following urinary catheterization and prompt medication in
      the emergency department. He was admitted to the neurology ward with a diagnosis
      of acute urinary outflow obstruction resulting in ARF due to detrusor dysfunction
      complicating an MS attack. ARF may complicate the course of patients with MS and
      associated detrusor-external sphincter dyssynergia. Renal recovery of these
      patients may be facilitated by urinary catheterization and supportive treatment.

PMID- 15856858
TI  - Do the residents in the emergency department appropriately manage patients with
      acute asthma attack? A study of self-criticism.
AB  - The objective of this study was to investigate the management of patients with
      asthma attack admitted to the emergency department (ED) in terms of compliance
      with international guidelines. The records of patients with asthma who were
      admitted to a university-based ED between December 2001 and December 2002 were
      evaluated. A total of 72 cases with available data were evaluated
      retrospectively. Twenty-six patients (36.1%) were admitted more than once during
      the study period. The number of multiple admissions ranged from 2 (15 patients,
      20.0%) to 11 (2 patients, 2.8%). Peak expiratory flow (PEF) measurements were
      recorded in 17 patients (23.6%) on presentation. Pulse and respiratory rates were
      recorded in 70 (97.0%) and 67 patients (93.0%), respectively. Thirty-four
      patients (47.2%) underwent chest x-ray; results were normal in most patients.
      Salbutamol was the most commonly used drug as first-line therapy. Ipratropium
      bromide (inhaled) and systemic corticosteroids were added to the salbutamol in 47
      (65.2%), 42 (58.4%), and 32 patients (44%), respectively. Pulmonologists were
      consulted in only 7 cases (9.7%). Thirty patients (43.4%) were prescribed
      corticosteroids on discharge. The role of functional parameters in determining
      asthma severity and monitoring treatment effects should be emphasized in clinical
      practice. Finally, more prevalent use of management guidelines will help
      determine their usefulness.

PMID- 15856859
TI  - Therapeutic profile of manidipine and lercanidipine in hypertensive patients.
AB  - Manidipine and lercanidipine are considered effective and safe in the treatment
      of chronic arterial hypertension and are equipotent in reducing blood pressure
      (BP) levels. Their main side effect is ankle-foot edema. After a 2-week placebo
      run-in period, these 2 drugs were compared in a controlled parallel-group study
      lasting 3 months, involving 53 patients with mild-to-moderate essential
      hypertension (26 assigned to manidipine and 27 to lercanidipine). At the end of
      the active treatment period, BP was significantly reduced in comparison with the
      end of the placebo phase in both the manidipine and the lercanidipine groups,
      without significant differences between the 2 drugs. Daytime BP was significantly
      reduced by 5.5%/5.6% with manidipine and by 3.8%/6.6% with lercanidipine, while
      smaller reductions were seen at nighttime. The smoothness index was the same with
      both drugs. Unlike lercanidipine, manidipine significantly reduced both basal (
      30%) and minimal vascular resistance (-39%), qualifying it as a potent
      vasodilator. Despite vasodilation, heart rate was not increased but was even
      slightly reduced by treatment. Ankle-foot edema was observed with both drugs but
      was less pronounced with manidipine, probably because of greater postcapillary
      dilatation. In conclusion, manidipine and lercanidipine are both effective and
      safe in mild-to-moderate essential hypertension, although the former seems to
      have a more favorable tolerability profile than the latter.

PMID- 15856860
TI  - The efficacy of bimatoprost 0.03% monotherapy in patients previously using
      topical beta-blocker monotherapy for the treatment of glaucoma or ocular
      hypertension.
AB  - In an open-label 12-week study, the safety and efficacy of bimatoprost 0.03% was
      evaluated in 55 patients with open-angle glaucoma or ocular hypertension
      inadequately controlled by topical beta-blocker monotherapy. Patients
      discontinued their topical beta-blocker therapy at the baseline visit and began
      bimatoprost monotherapy that evening. Study visits were at 6 and 12 weeks
      postbaseline. Bimatoprost reduced intraocular pressure (IOP) 4.5 mm Hg (21.5%; P
      < .001) from baseline at week 6 and 4.2 mm Hg (19.6%; P < .001) at week 12.
      Patients were more likely to achieve low target pressures with bimatoprost than
      with topical beta-blockers. Conjunctival hyperemia was the most commonly reported
      adverse event. The findings from this study indicate bimatoprost monotherapy
      provides a substantially greater IOP reduction than topical beta-blocker therapy
      and allows more patients to achieve a low target pressure. Bimatoprost is an
      effective alternative to topical beta-blockers for the treatment of glaucoma and
      ocular hypertension.

PMID- 15856861
TI  - Analysis of factors affecting satisfaction in the emergency department: a survey
      of 1019 patients.
AB  - The objective of this study was to identify factors that affect overall
      satisfaction of patients admitted to the emergency department (ED). All
      consecutive adult patients in the ED during a 14-day period who could communicate
      well were enrolled into this cross-sectional analytic study. Patients'
      demographic data, information on care, and level of satisfaction were recorded.
      Patients were asked to rate specific issues concerning their satisfaction (good
      and excellent) on a 5-point Likert scale. Response to the survey was obtained
      from 1019 (91.6%) of 1113 patients for analysis during the study. Satisfaction
      with physician experience, physician attitude, triage, explanation of health
      status and treatment, and discharge instructions were found to have significant
      impact on satisfaction (P < .001 for each). Satisfaction with physician
      experience level was the most important factor affecting overall satisfaction.
      Patient perception of the total time spent in the ED as "short" and "very short"
      was not demonstrated to be significantly related to overall satisfaction (P =
      .162). Temporal perceptions as "long" and "very long" were shown to be
      significantly related to overall satisfaction (P < .001). Behavioral
      characteristics of the healthcare providers and the hospital itself were the
      factors that had the greatest impact on overall satisfaction of the ED population
      evaluated.

PMID- 15856862
TI  - Implantable direct current stimulation in para-axial cervical arthrodesis.
AB  - This retrospective, case-controlled pilot study was designed to examine the
      efficacy and safety of an implantable direct current bone growth stimulator
      (IDCBGS) as an adjunct to cervical arthrodesis in patients at high risk for
      nonunion after undergoing cervical fusion in region from the occiput to C3.
      Twenty patients underwent para-axial cervical arthrodesis (involving posterior
      spine fusion and instrumentation using standard surgical techniques) for the
      correction of instability. All were at high risk for nonunion due to advanced
      age, rheumatoid arthritis, prior failed fusion attempts, infection, or
      immunosuppressive drug use. An IDCBGS was used to augment the surgical procedure.
      The mean follow-up period was 19 months, and 16 patients were available for
      follow-up. Radiographic evidence of fusion was demonstrated in 15 of 16 patients
      (94%). After surgery, all patients demonstrated clinical stabilization, a
      resolution of symptoms in combination with an improvement in neurologic status,
      or both. The mean elapsed time before fusion occurred was 4.6 months. No
      neurologic complications related to cathode or generator placement were observed.
      The use of the stimulator as an adjunct to instrument- or non-instrument-assisted
      surgical fusion of the para-axial region in these high-risk patients appeared
      both safe and efficacious. Further investigation is warranted to define the
      possible role and clinical utility of the IDCBGS in selected patients requiring
      cervical fusion, particularly those at high risk for nonunion.

PMID- 15856863
TI  - Axenic cultivation of Entamoeba dispar in newly designed yeast extract-iron
      gluconic acid-dihydroxyacetone-serum medium.
AB  - Yeast extract-iron-gluconic acid-dihydroxyacetone-serum medium that allows axenic
      cultivation of Entamoeba dispar was designed based on casein-free yeast extract
      iron-serum (YI-S) medium, and the usefulness of the medium was assessed. The main
      differences from YI-S medium are replacement of glucose by gluconic acid,
      addition of dihydroxyacetone and D-galacturonic acid monohydrate, and
      sterilization by filtration. This medium promoted the axenic growth of 5 strains
      of E. dispar (2 strains of nonhuman primate isolates and 3 strains of human
      isolates). In addition, to clarify the biological basis for the growth of E.
      dispar in this medium, analyses of relevant enzymes on the glycolytic pathway of
      the amoebae as well as of the protozoans that are the best culture supplement for
      amoebae are being performed.

PMID- 15856864
TI  - Trichomonas vaginalis: identification of soluble and membrane-associated
      phospholipase A1 and A2 activities with direct and indirect hemolytic effects.
AB  - A direct hemolytic activity, dependent on phospholipase A (PLA) activity, was
      located in the particulate subcellular fraction (P30) of Trichomonas vaginalis.
      We identified soluble direct and indirect hemolytic activities in the spent
      medium and soluble fraction (S30) of T. vaginalis strain GT-13. Spent medium
      showed the highest specific indirect hemolytic activity (SIHA) at pH 6.0 (91
      indirect hemolytic units [HU]/mg/hr). Spent medium and P30, but not S30, showed
      direct hemolytic activity. PLA activity was protein dose dependent and time
      dependent. The highest PLA activity was observed at pH 6.0. All trichomonad
      preparations showed phospholipase A1 (PLA A1) and phospholipase A2 (PLA A2)
      activities. Indirect and direct hemolytic activity and PLA A1 and PLA A2
      diminished at pH 6.0 and 8.0 with increasing concentrations of Rosenthal's
      inhibitor. The greatest effect was observed with 80 microM at pH 6.0 on the SIHA
      of S30 (83% reduction) and the lowest at pH 8.0, also on the SIHA of S30 (26%
      reduction). In conclusion, T. vaginalis contains particulate and soluble acidic,
      and alkaline direct and indirect hemolytic activities, which are partially
      dependent on alkaline or acidic PLA A1 and PLA A2 enzymes. These could be
      responsible for the contact-dependent and -independent hemolytic and cytolytic
      activities of T. vaginalis.

PMID- 15856865
TI  - Susceptibility of inbred mouse strains to infection with three species of
      Metagonimus prevalent in the Republic of Korea.
AB  - Susceptibility of inbred mouse strains to Metagonimus yokogawai, Metagonimus
      miyatai, and Metagonimus takahashii infections was studied using BALB/c, ddY,
      C57BL/6J, C3H/HeN, and A/J mice, with H-2 haplotypes d, s, b, k, and a,
      respectively. Two hundred metacercariae were orally fed to each mouse, and the
      worm recovery rates (WRR), worm dimensions, and intrauterine egg numbers were
      measured at days 3, 7, 14, 21, and 28 postinfection (PI). On day 14 PI, the WRR
      of M. yokogawai was highest in ddY mice (average, 62.2%); those of M. miyatai and
      M. takahashii were highest in ddY (19.5%) and BALB/c mice (10.4%), respectively;
      worm maturation was best in C3H/HeN (M. yokogawai), C57BL/6J (M. miyatai), and
      ddY mice (M. takahashii). All mouse strains showed higher susceptibility to
      infection with M. yokogawai than with M. miyatai or M. takahashii. The results
      show that susceptibility of mice to Metagonimus infection varies according to
      mouse strain and parasite species but is suggested to be independent of the mouse
      H-2 haplotype.

PMID- 15856866
TI  - Autofluorescence of Toxoplasma gondii and Neospora caninum cysts in vitro.
AB  - Autofluorescence of Toxoplasma gondii and Neospora caninum was studied by
      fluorescence microscopy during their differentiation from tachyzoites to
      bradyzoites in vitro using Vero as host cells. Stage conversion into bradyzoites
      and cysts was confirmed by immunofluorescent microscopy and Western blot analysis
      using SAG1- and BAG1-specific antibody, respectively. From day 4 postinfection
      (PI), pale blue autofluorescence of the bradyzoites and tissue cysts was observed
      with UV light at 330-385 nm, which coincided with the onset of cyst development.
      This autofluorescence under UV light of bradyzoites and tissue cysts increased in
      intensity from days 8 to 10 PI. In contrast to the autofluorescence shown by
      bradyzoites and cysts, tachyzoites and parasitophorous vacuoles containing
      tachyzoites never autofluoresced at any time examined. Autofluorescence of the
      cystic stages was of sufficient intensity and duration to allow the detection of
      cysts and bradyzoites of T. gondii and N. caninum. In this study, we describe for
      the first time the autofluorescence properties of in vitro-induced bradyzoites
      and cysts of T. gondii and N. caninum.

PMID- 15856867
TI  - Age-dependent epidemiological patterns and strain diversity in helminth
      parasites.
AB  - Field studies of schistosomes and the major intestinal nematodes Trichuris
      trichiura and Ascaris lumbricoides repeatedly demonstrate that the intensity and
      prevalence of infection exhibit marked dependency on host age. Peak levels of
      infection typically occur in hosts aged between 10 and 14 yr in endemically
      infected communities. It has widely been assumed that the slow acquisition of
      resistance in adults is caused by repeated exposure to the same antigenic
      repertoire of a single parasite strain. Consequently, these empirical patterns
      have previously been taken to suggest that human immunity to helminth parasites
      confers poor protection against reinfection. Here, an alternative explanation is
      suggested on the basis of results from a simplified model of helminth
      transmission. It is proposed that the empirical observations can be attributed to
      the circulation of multiple helminth strains that each elicit highly protective
      immunity. If this hypothesis is correct, estimates of epidemiological parameters
      from field data and the potential for control of helminth diseases might require
      reevaluation.

PMID- 15856868
TI  - Parasite prevalence and the size of host populations: an experimental test.
AB  - Although important in epidemiological theory, the relationship between the size
      of host populations and the prevalence of parasites has not been investigated
      empirically. Commonly used models suggest no relationship, but this prediction is
      sensitive to assumptions about parasite transmission. In laboratory populations,
      I manipulated the size of Tribolium castaneum flour beetle populations and
      measured the prevalence and distribution of a parasitic mite, Acarophenax
      tribolii. I found that parasite prevalence did not vary for a wide range of host
      population sizes. However, prevalence was lower in populations with less than 40
      hosts. This effect cannot be attributed to changes in host population density
      because host density was held constant among treatments. The reduction in
      prevalence of small populations below a threshold that I observed is predicted by
      the extinction debt model, but it is not expected from models of host-parasite
      interactions that assume density-dependent transmission. The distribution of
      parasites, measured using Lloyd's patchiness index, was not affected by host
      population size. The mean crowding of parasites, however, was negatively related
      with host density. Finally, the prevalence of parasites in large populations did
      not differ from that found in sets of smaller patches as long as the smaller
      populations in aggregate were equivalent in size to the large population.

PMID- 15856869
TI  - Infracommunity structure of parasites of Hemigymnus melapterus (Pisces: Labridae)
      from Lizard Island, Australia: the importance of habitat and parasite body size.
AB  - This study describes the community of all metazoan parasites from 14 individuals
      of thicklip wrasse, Hemigymnus melapterus, from Lizard Island, Australia. All
      fish were parasitized, and 4,649 parasite individuals were found. Twenty-six
      parasite species were identified although only 6 species were abundant and
      prevalent: gnathiid isopods, the copepod Hatschekia hemigymni, the digenean
      Callohelmis pichelinae, and 3 morphotypes of tetraphyllidean cestode larvae. We
      analyzed whether the body size and microhabitat of the parasites and size of the
      host affected understanding of the structure of the parasite community. We
      related the abundance, biovolume, and density of parasites with the host body
      size and analyzed the abundances and volumetric densities of some parasite
      species within microhabitats. Although the 2 most abundant species comprised 75%
      of all parasite individuals, 4 species, each in similar proportion, comprised 85%
      of the total biovolume. Although larger host individuals had higher richness,
      abundance, and biovolume of parasites than smaller individuals, overall parasite
      volumetric density actually decreased with the host body size. Moreover,
      parasites exhibited abundances and densities significantly different among
      microhabitats; some parasite species depended on the area available, whereas
      others selected a specific microhabitat. Parasite and habitat size exhibited
      interesting relationships that should be considered more frequently.
      Considerations of these parameters improve understanding of parasite community
      structure and how the parasites use their habitats.

PMID- 15856870
TI  - Laelapine mites (Acari: Laelapidae) associated with small mammals from Amazonas,
      Brazil, including a new species from marsupials.
AB  - An intensive survey of ectoparasitic arthropods associated with small mammals in
      upland forests near Manaus, Brazil, provides information on the taxonomy and host
      distribution of laelapine mites in the Amazonian Region. We identified 5 genera
      and 21 species of these mites by comparison with representative museum specimens,
      the taxonomic literature, and, when possible, the original type specimens. These
      mites are host specific, with associations ranging from strict monoxeny (18
      species) to oligoxeny (1 species) and pleioxeny (2 species). Marsupials were
      infested with species of Androlaelaps, echimyid rodents with Tur, and
      sigmodontine rodents with Gigantolaelaps, Laelaps, and Mysolaelaps. Androlaelaps
      bergalloi, a new species of Laelapinae, is described from the pelage of the
      marsupial Monodelphis brevicaudata.

PMID- 15856871
TI  - Bolivian ectoparasites: a new species of laelapine mite (Acari: Parasitiformes,
      Laelapidae) from the rodent Neacomys spinosus.
AB  - Laelaps neacomydis n. sp. is described from the pelage of the rodent Neacomys
      spinosus collected in Bolivia. Collection records from northern Brazil,
      southeastern Peru, and central Bolivia indicate its wide distribution across
      Amazonas associated with rodents of the genus Neacomys. The formal taxonomic
      description and illustrations are derived from the adults (female and male). Two
      larger species of laelapine mites, Gigantolaelaps intermedius and L. boultoni,
      infest the same hosts at the same localities.

PMID- 15856872
TI  - The severity of whirling disease among wild trout corresponds to the differences
      in genetic composition of Tubifex tubifex populations in central Colorado.
AB  - We analyzed the geographic distribution of Tubifex tubifex from various river
      drainages in central Colorado by genetic screening with specific mitochondrial
      16S ribosomal DNA (mt 16S rDNA) markers. Four distinct mt 16S rDNA lineages are
      evident. The sites varied with respect to land- and water-use practices. All
      sites represented habitats presumed capable of supporting oligochaetes. At the
      locations where whirling disease has had the greatest impact on resident rainbow
      trout, T. tubifex, representing lineages I and III (genotypes known to be
      susceptible to Mxyobolus cerebralis), were most commonly found. In contrast, at
      sites less affected by whirling disease, T. tubifex of lineages V and VI that are
      more resistant to M. cerebralis infections were more abundant. The predominance
      of resistant T. tubifex worms (lineages V and VI) at low-impact sites supports
      the conclusion that when these genotypes are in greater abundance, the potential
      for more severe effects of whirling disease on wild rainbow trout populations may
      be diminished.

PMID- 15856873
TI  - New oral linguiform projections and their associated neurons in the third-stage
      infective larva of the parasitic nematode Oesophagostomum dentatum.
AB  - The infective larvae (L3i) of the nematode parasite of swine, Oesophagostomum
      dentatum, are passively ingested by their hosts. The L3i exhibit certain
      behaviors that are probably selected to increase the likelihood of ingestion, by
      strategic positioning in the environment. The larvae show positive geotactic
      behavior and respond to temperature variations in their environment, as shown by
      their behavior on a thermal gradient. To investigate neuronal control of this
      behavior, we initiated a study of the structure of the amphidial neurons of this
      parasite. The same number and types of neuronal dendritic processes are found in
      the amphids of the O. dentatum L3i as in those of its close relatives Haemonchus
      contortus and Ancylostoma caninum. Well-developed dendritic processes of wing
      cells are located in the amphidial sheath cells, these being similar to wing
      cells AWA in the free-living nematode Caenorhabditis elegans but actually more
      extensive. Similar to its close relatives just mentioned, and C. elegans as well,
      O. dentatum L3i has prominent finger cell processes, the finger cell neurons
      being the thermoreceptors in all 3 of the preceding species. However, unlike the
      arrangement seen in H. contortus and A. caninum, where the microvilli-like
      "fingers" of these neurons lie dorsal to the amphidial channel and occupy a very
      large portion (>50%) of the anterior end of the larva, the dendritic process of
      the finger cells in O. dentatum extends into unusual linguiform projections that,
      in turn, extend into the lumen of the mouth tube, a complex structural
      arrangement that has not been described for any other nematode.

PMID- 15856874
TI  - First biologic and genetic characterization of Toxoplasma gondii isolates from
      chickens from Africa (Democratic Republic of Congo, Mali, Burkina Faso, and
      Kenya).
AB  - The prevalence of Toxoplasma gondii in free-ranging chickens (Gallus domesticus)
      is a good indicator of the prevalence of T. gondii oocysts in the soil because
      chickens feed from the ground. In the present study, prevalence of T. gondii in
      chickens from Democratic Republic of Congo, Mali, Burkina Faso, and Kenya is
      reported. The prevalence of T. gondii antibodies in sera of 50 free-range
      chickens from Congo was 50% based on the modified agglutination test (MAT);
      antibody titers were 1:5 in 7, 1:10 in 7, 1:20 in 6, 1:40 in 1, and 1:160 or more
      in 4 chickens. Hearts, pectoral muscles, and brains of 11 chickens with titers of
      1:20 or more were bioassayed individually in mice; T. gondii was isolated from 9,
      from the hearts of 9, brains of 3, and muscles of 3 chickens. Tissues of each of
      the 14 chickens with titers of 1:5 or 1:10 were pooled and bioassayed in mice; T.
      gondii was isolated from 1 chicken with a titer of 1:10. Tissues from the
      remaining 25 seronegative chickens were pooled and fed to 1 T. gondii-free cat.
      Feces of the cat were examined for oocysts, but none was seen. The results
      indicate that T. gondii localizes in the hearts more often than in other tissues
      of naturally infected chickens. Genotyping of these 10 isolates using the SAG2
      locus indicated that 8 were isolates were type III, 1 was type II, and 1 was type
      I. Two isolates (1 type I and 1 type III) were virulent for mice. Toxoplasma
      gondii was isolated by mouse bioassay from a pool of brains and hearts of 5 of 48
      chickens from Mali and 1 of 40 chickens from Burkina Faso; all 6 isolates were
      avirulent for mice. Genetically, 4 isolates were type III and 2 were type II.
      Sera were not available from chickens from Mali and Burkina Faso. Toxoplasma
      gondii antibodies (MAT 100 or more) were found in 4 of 30 chickens from Kenya,
      and T. gondii was isolated from the brain of 1 of 4 seropositive chickens; this
      strain was avirulent for mice and was type II. This is the first report on
      isolation and genotyping of T. gondii from any source from these 4 countries in
      Africa.

PMID- 15856875
TI  - Protective effect of antiganglioside antibodies against experimental Trypanosoma
      brucei infection in mice.
AB  - Liposome-associated ganglioside antigens (ganglioside GM1 or bovine brain
      gangliosides) were prepared to facilitate the potential protective efficacy for
      Trypanosoma brucei. Mice were immunized with liposome-associated ganglioside GM1
      or bovine brain gangliosides intraperitoneally (i.p.). After immunization,
      significantly higher antigen-specific IgG and IgM antibodies were detected in
      sera than in the nonimmunized control group. When sera from immunized mice were
      analyzed for isotype distribution, antigen-specific IgG1, IgG2a, and IgG3
      antibody responses were also noted. After immunization, mice were challenged i.p.
      with 1 x 10(2) cells of T. brucei. Sixty percentage of liposome-associated
      ganglioside GM1-immunized mice survived the infection, and all the mice immunized
      with bovine brain gangliosides-containing liposomes survived. However, all
      control mice died within 7 days after infection. These data demonstrate that
      liposomes containing ganglioside antigens have the potential usefulness for the
      induction of a protective immune response against T. brucei infection and suggest
      the possibility of developing vaccines that may ultimately be used for the
      prevention of trypanosomiasis.

PMID- 15856876
TI  - Comparative susceptibility of three important malaria vectors Anopheles
      stephensi, Anopheles fluviatilis, and Anopheles sundaicus to Plasmodium vivax.
AB  - The 3 laboratory-colonized malaria vectors, i.e., Anopheles stephensi, An.
      sundaicus, and An. fluviatilis, were studied for their comparative susceptibility
      to Plasmodium vivax sporogony. There was no significant difference in oocyst and
      sporozoite recruitment by these 3 species, whereas the geometric mean (GM) of the
      oocyst number per midgut was significantly lower in An. fluviatilis as compared
      with that in the other 2 species. There was no difference in the GM of oocyst
      between An. stephensi and An. sundaicus. Adaptability to laboratory conditions
      and susceptibility to plasmodial infection suggest that An. fluviatilis and An.
      sundaicus can also be used as a vector model for vector-parasite interaction
      studies.

PMID- 15856877
TI  - Tetraphyllidean plerocercoids from Western Mediterranean cetaceans and other
      marine mammals around the world: a comprehensive morphological analysis.
AB  - Tetraphyllidean plerocercoids have occasionally been reported in marine mammals,
      but they have rarely been described in detail, and the ecological significance of
      these infections is unclear. We described plerocercoids collected from the mucosa
      of the terminal colon and rectum, the anal crypts, and the hepatopancreatic ducts
      of 7 striped dolphins Stenella coeruleoalba, 1 Cuvier's beaked whale Ziphius
      cavirostris, and 3 Risso's dolphins Grampus griseus from the Spanish
      Mediterranean. We also examined undescribed plerocercoids from 3 cetacean species
      from the Atlantic and the Pacific. All plerocercoids had a lanceolate body, and a
      scolex with an apical sucker and 4 sessile monolocular bothridia. The bothridia
      had free posterior edges and an accessory sucker at their anterior end. Under
      light microscopy, the bothridia of some Mediterranean specimens looked bilocular
      without accessory suckers, but a true accessory sucker was observed in
      histological sections. A principal component analysis revealed 2 stable clusters
      of specimens along the first principal component regardless of host species.
      These "large" and "small" morphotypes are thought to represent early migratory
      stages of Phyllobothrium delphini and Monorygma grimaldii. The similarity in
      scolex morphology, the observation of plerocercoids buried in intestinal regions
      close to the sites where M. grimaldii and P. delphini occur, and the coexistence
      of all larval forms in the same individual hosts would support this hypothesis.
      Future molecular analysis may confirm it.

PMID- 15856878
TI  - Alternative reproductive strategies in the progenetic trematode Coitocaecum
      parvum: comparison of selfing and mating worms.
AB  - The progenetic opecoelid trematode Coitocaecum parvum can reproduce either
      precociously by selfing in its second intermediate amphipod host or by mating in
      its normal definitive fish host. In this study, we describe and compare the
      infection parameters and some life history traits of both egg-producing worms and
      non-egg producing worms in both their second intermediate and definitive hosts.
      We showed that 58% of worms start to produce eggs while still in the amphipod.
      The relative abundance of progenetic worms increased with amphipod size, and egg
      producing worms achieved greater size in amphipods than in fish. These 2 findings
      support the reproductive insurance hypothesis. No difference in size was revealed
      between eggs produced in the amphipods and those produced in the fish. Although
      more information is needed to thoroughly assess the respective costs and benefits
      of selfing and mating in this species, our conclusion is that adopting progenesis
      may have few, if any, long-term negative consequences for the parasite.

PMID- 15856879
TI  - A new species of Oochoristica (Eucestoda: Cyclophyllidea) parasite of Ctenosaura
      pectinata (Reptilia: Iguanidae) from Oaxaca, Mexico.
AB  - During January 2002, 3 specimens of an undescribed species of Oochoristica Luhe,
      1898, were collected in Ctenosaura pectinata (Wiegmann, 1834) from Santa Mara
      Mixtequilla, Oaxaca, Mexico. Oochoristica leonregagnonae n. sp. differs from 71
      of 82 species of the genus by its large number of testes (78-112 [95] vs. less
      than 65 per proglottid, respectively). In addition, the numerous ovarian lobes
      (31-79 [51]) possessed by the new species distinguish it from the other 10, with
      a maximum of 20 ovarian lobes. The new species differs from Oochoristica
      acapulcoensis Brooks, Perez-Ponce de Leon and Garcia-Prieto, 1999, which also
      infects C. pectinata in Mexico, by the presence of numerous staining granules
      throughout the parenchyma of the scolex in the latter species; likewise, testes
      in O. acapulcoensis reach and even overpass the excretory canals, whereas in the
      new species they are limited to the central region between these tubules.

PMID- 15856880
TI  - A new species of Skrjabingylus Petrov, 1927 (Nematoda: Metastrongyloidea) from
      the frontal sinuses of the hooded skunk, Mephitis macroura (Mustelidae).
AB  - Skrjabingylus santaceciliae n. sp. is described based on specimens from the
      frontal sinuses of a hooded skunk, Mephitis macroura, collected from the Area de
      Conservacion Guanacaste, Costa Rica. Skrjabingylus santaceciliae n. sp. differs
      from the other 5 species in the genus in having pointed spicule tips that lack a
      rounded or lobed formation and by lacking a prominent distal projection at the
      tail tip. Morphometric comparisons show that S. santaceciliae n. sp. is much
      smaller than the only other valid species from Mephitis, Skrjabingylus
      chitwoodorum Hill, 1939. Likewise, morphometric comparisons also distinguish S.
      santaceciliae n. sp. from other described Skrjabingylus species.

PMID- 15856881
TI  - A new genus and species of cyclocoelid from the black-necked stilt, Himantopus
      mexicanus (Recurvirostridae), from Galveston, Texas.
AB  - Two black-necked stilts, Himantopus mexicanus (Recurvirostridae), from the Texas
      Gulf coast, died while in the care of bird rehabilitators and were found to be
      infected with Neoallopyge americanensis n. gen., n. sp. Neoallopyge n. gen.
      (Digenea: Cyclocoelidae) differs from Allopyge in having the testes situated some
      distance from the posterior extremity, 2 uterine loops on each side extensively
      invading the space posterior to the testes, no intertesticular uterine loops, and
      it is a parasite of Recurvirostridae in the western hemisphere rather than
      Gruidae from the Old World. The new species is unlike Allopyge antigones,
      Allopyge ominosus, and Allopyge undulatus in having the genital pore located
      anterior to the cecal bifurcation rather than posterior to it, and it is unlike
      A. ominosus and A. undulatus, where the uterus is entirely intercecal in having
      the uterine loops extending laterally, reaching the body wall on both sides. The
      new species further differs from A. antigones, A. ominosus, and Allopyge
      skrjabini in having larger eggs (148 [140-155] microm by 55 [45-63] microm
      compared with 95 by 55 microm, 65-80 by 40-46 microm, 119-124 by 55-66 microm,
      respectively), and it differs from Allopyge adolphi and A. undulatus in having
      narrower eggs (154 by 75 microm, 144 by 86 microm, respectively).

PMID- 15856882
TI  - Two new genera of the pharyngodonidae (Nematoda: Oxyuroidea) found in rhacophorid
      frogs of the Ryukyu Archipelago, Japan.
AB  - Okinawandros goldbergi n. gen., n. sp. and Ataronema sekii n. gen., n. sp.
      (Nematoda: Pharyngodonidae) are described from rhacophorid frogs of the Ryukyu
      Archipelago, Japan. Okinawandros n. gen. resembles Batracholandros Freitas et
      Ibanez, 1965 and Synodontisia Petter, Vassiliades et Troncy, 1972 but is readily
      distinguished from the former in lacking laterally situated genital papillae and
      by having anteriorly directed vagina and from the latter by having operculated
      eggs and lacking a spicule. Ataronema n. gen. most closely resembles
      Parathelandros Baylis, 1930 but is readily distinguished because the posterior
      pair of caudal papillae is not rosette shaped and the eggs are not operculated.
      Morphological notes of Pharyngodon polypedatis Yamaguti, 1941 are included.

PMID- 15856883
TI  - A redescription of the Australian leech Placobdelloides bancrofti with new
      records of its distribution.
AB  - Placobdelloides bancrofti (Best, 1931) Sawyer, 1986 (Euhirudinea:
      Glossiphoniidae) is recorded for the first time from a location in North
      Queensland, Australia. Placobdelloides bancrofti was found feeding on the
      freshwater turtle Emydura krefftii and was collected from a new host species
      Elseya latisternum. Examination of live individuals enabled us to document
      external coloration and markings for the first time. Clarification of the
      original description of P. bancrofti is made, correcting the location of the anal
      pore, and then the taxonomic history of this species is discussed.

PMID- 15856884
TI  - A specific primer pair for the diagnosis and identification of Acanthamoeba
      astronyxis by random amplified polymorphic DNA-polymerase chain reaction.
AB  - Random amplified polymorphic DNA (RAPD) is a useful tool for species
      identification. The obtained band patterns can be used for specific primer pair
      design that is useful for species identification. In this study, a distinctive
      485-bp band in Acanthamoeba astronyxis band patterns was found, using the OPC20
      primer (ACTTCGCCAC). The band specificity was confirmed by hybridization, using
      it as a probe, against all OPC20 amplifications from different Acanthamoeba
      species. Once the fragment was sequenced, we used it to design a specific primer
      pair that was useful for the identification of different isolates as A.
      astronyxis species.

PMID- 15856885
TI  - Redescription of Trichuris pampeana (Nematoda: Trichuridae) from the South
      American subterranean rodent Ctenomys talarum Thomas, 1898 (Rodentia:
      Octodontidae).
AB  - Trichuris pampeana Suriano and Navone, 1994 (Nematoda: Trichuridae) is
      redescribed from voucher specimens from the type host Ctenomys azarae Thomas,
      1903 (Rodentia: Octodontidae) and from parasites collected from 2 populations of
      the subterranean rodent C. talarum Thomas, 1898 from Mar de Cobo and Necochea,
      Buenos Aires Province, Argentina. After a revision of these nematodes, it was
      confirmed that the following characters were not considered in the original
      description: bacillary band, cells from the esophagointestinal junction,
      ejaculatory duct, vas deferens, adanal papillae, vagina, oviduct, and rectum.
      Additional information about the spicular sheath, vulva, uteri, and ovary is
      provided. The morphological features given in this redescription allow to confirm
      the identity of T. pampeana as a valid species and also to distinguish it more
      clearly from other species of the genus.

PMID- 15856886
TI  - Haemoproteids of the avian family Dicruridae (the drongos).
AB  - Dicrurids are a widespread avian family in Africa and Asia. Earlier surveys of
      this family in these areas have reported the presence of hematozoa and 1 species
      of Haemoproteus, i.e., Haemoproteus dicruri (De Mello, 1935). One species of
      drongo occurs in Madagascar and has not been examined previously. Blood smears
      collected from wild-caught crested drongos, Dicrurus forficatus, in Madagascar
      were examined using a compound microscope for the presence of hematozoa. A new
      species, Haemoproteus khani, is described in this study. This new species has
      circumnuclear gametocytes, in contrast to the halteridial H. dicruri. In
      addition, H. dicruri is reported for the first time from the crested drongo and
      is redescribed. This is the first report of hematozoa in drongos of Madagascar.

PMID- 15856887
TI  - A Haemocystidium species from the East African gecko Lygodactylus capensis
      grotei.
AB  - Haemocystidium lygodactyli n. sp. parasitizes Lygodactylus capensis grotei
      (Gekkonidae) in Tanzania. Mature gametocytes in acute phase of infection average
      16.3 x 5.7 microm (11-20 x 4-9.5 microm), with LW 93.0 (62-140 microm2) and L/W
      ratio 2.94 (1.2-3.9). Gametocytes usually lateral, lateropolar, or halteridial in
      position. There was no significant sexual dimorphism in gametocyte dimensions.
      Nuclei discrete in both sexes at maturity, with a rounded nucleolus usually
      present in microgametocytes. In chronic infection, gametocytes were 18.1 x 8.7
      microm (8-25 x 5-11 microm), with LW 156.8 microm2 (80-250) and L/W 2.16 (1.1
      3.6). When gametocytes from the chronic infection were compared with the same sex
      in acute infection, length did not differ, but differences were present between
      the same sex in each comparison of width, LW, and L/W. Macrogametocytes and
      microgametocytes in chronic phase were broader, larger, and less elongate and
      most commonly halteridial. Meronts were found only in endothelium and connective
      tissue of lung. Elongate to oval in shape, the larger meronts filled with nuclei
      were 12.2 x 6.9 microm (10.0 x 5.0-16.0 x 9.0), with LW 50-144 microm2 (85.1). In
      1 initial infection followed for 49 days, apparently mature gametocytes appeared
      by day 28 postcapture. Binucleate parasites were present from day 14 throughout
      the course of infection, with their frequency increasing from 5% of immature
      parasites to 34% of mature gametocytes. Binucleate mature gametocytes were found
      in 1 other infection, where 14% had 2 nuclei. Sex ratio varied from 51 to 63% in
      favor of macrogametocytes.

PMID- 15856888
TI  - Two additional Hepatozoon species (Apicomplexa: Hepatozoidae) from the southern
      black racer, Coluber constrictor priapus (Serpentes: Colubridae), in northern
      Florida.
AB  - Hepatozoon priapus n. sp. from Coluber constrictor priapus has robust gamonts
      with broadly rounded ends, 18.0 x 4.2 microm (17.0-20.0 x 3.5-6.0), with LW 76.4
      microm2 (59-105) and L/W 4.31 (2.9-5.4). The nucleus is always present in second
      quarter of gamont, seldom extend into first quarter but often into third quarter,
      6.0 x 3.0 (5.0-7.0 x 2.5-4.0), with LW 17.9 (13.7-21.0). Erythrocyte cytoplasm is
      always thin, appearing dehemoglobinized, with infected cells always distorted.
      Infected erythrocytes are much longer and wider than uninfected cells, with
      longer nuclei. Oocysts are spherical to ovoid, 92.5 x 86.0 (55-123 x 47-115) and
      L/W 1.08 (1.0-1.3), contain 14.0 (6-31) sporocysts. Sporocysts, which are also
      spherical to ovoid, 26.3 x 23.3 (19-50 x 16-38), LW 641.2 (320-1,500) and L/W
      1.13 (1.0-2.2), contain 12.6 (5-18) sporozoites. Hepatozoon confusus n. sp., also
      from C. constrictor priapus, has slender gamonts with rounded ends, 15.6 x 4.1
      (14.0-17.0 x 3.5-5.0), with LW 64.3 (52-80) and L/W 3.82 (2.8-4.4). The nucleus
      is always present in second quarter of gamont, commonly extending into first and
      third quarters, 5.0 x 2.7 (2.5-4.4 x 4.0-6.0), with LW 13.5 (11.0-16.5).
      Erythrocyte cytoplasm is sometimes thin, appearing partially dehemoglobinized,
      with infected cells usually distorted. Infected erythrocytes are longer than
      uninfected cells but similar in width, with erythrocyte nuclei longer. Oocysts
      are spherical to ovoid, 115.5 x 108.9 (52-278 x 50-278), with L/W 1.06 (1.0-1.2),
      and contain 25.0 (7-111) sporocysts. Sporocysts are spherical to ovoid, 27.6 x
      25.2 (21-38 x 20-33), LW 701.3 (420-1,125) and L/W 1.09 (1.0-1.4), containing
      20.2 (12-32) sporozoites.

PMID- 15856889
TI  - Hepatozoon polytopis n. sp. parasitic in two genera and species of colubrid
      snakes in southern Florida.
AB  - Hepatozoon polytopis, described from Coluber constrictor priapus from Palm Beach
      County, Florida, has short, usually broad gamonts 12.8 x 4.6 microm (10.0-15.0 x
      3.5-6.0), with LW 58.5 microm2 (42-84) and L/W 2.84 (1.8-3.7). Nuclei commonly
      extend into first quarter of gamont (45%), are always present in second quarter,
      and seldom in third quarter (11%), with dimensions 4.5 x 3.4 (3.0-6.0 x 2.5-4.5)
      and LW 15.1 (10.0-24.0). Spherical to ovoid oocysts, 122.1 x 104.9 (62-240 x 57
      190), with L/W 1.17 (1.0-1.9), contain 31.3 (3-103) sporocysts. Spherical to
      ovoid sporocysts, 38.0 x 33.9 (28-73 x 25-58), with LW 1,325.1 (756-4,168) and
      L/W 1.12 (1.0-1.4), contain 42.9 (22-64) sporozoites. Thamnophis sauritus
      sackenii from Palm Beach County is infected also by H. polytopis, as indicated
      from similar gamont dimensions and verified by isolation of an identical
      haplotype of the 18S ribosomal RNA gene from both host species.

PMID- 15856890
TI  - Two Plasmodium species of the crocodile skink Tribolonotus gracilis from Irian
      Jaya, Indonesia.
AB  - Two undescribed Plasmodium species were present in 1 of 8 New Guinea skinks,
      Tribolonotus gracilis. Plasmodium tribolonoti n. sp. is characterized by rounded
      or oblong schizonts 6.1 x 5.3 microm (5-7 x 4-7) that produce on average 14.3
      merozoites (10-21), in no particular arrangement of nuclei. All parasitized
      proerythrocytes and had no effect upon dimensions of host cells or their nuclei.
      Gametocytes, mostly erythrocytic, averaged 7.2 x 6.3 (6.5-9.0 x 5.5-7.5), with
      length x width (LW) 45.5 microm2 (38-63) and L/W 1.15 (1.0-1.5). Gametocytes are
      not sexually dimorphic in size or shape and had no effect upon dimensions of host
      erythrocytes or their nuclei. Schizonts of P. gracilis n. sp. averaged 4.3 x 3.5
      (3-6 x 3-5), with 4.9 merozoites (3-8) usually arranged as a fan, and had no
      effect upon dimensions of host erythrocytes or their nuclei. Gametocytes averaged
      5.9 x 5.5 (5.0-6.6 x 5.0-6.0), with LW 31.9 microm2 (25-40) and L/W 1.06 (1.0
      1.2). Gametocytes are not sexually dimorphic in size or shape and had no effect
      upon dimensions of host erythrocytes or their nuclei.

PMID- 15856891
TI  - Glugea vincentiae n. sp. (Microsporidia: Glugeidae) infecting the Australian
      marine fish Vincentia conspersa (Teleostei: Apogonidae).
AB  - A parasite of the marine fish Vincentia conspersa was examined by light
      microscopy and transmission electron microscopy. This parasite develops in the
      subcutaneous tissue of the body and fins, forming spherical xenomas about 1-2 mm
      in diameter surrounded by a layer of amorphous material. The observed
      characteristics of the new parasite are in line with those of the other Glugea
      species; merogony takes place in the outer zone of the cytoplasm of the host
      cell, sporogony takes place in sporophorous vesicles, and mature spores are
      located in the central part of the xenoma. Meronts were cylindrical uninucleate
      or occasionally triradiate multinucleate, with plasmodia in direct contact with
      the host cytoplasm. Sporogonic plasmodia divided by multiple cleavage to produce
      sporoblast mother cells, which after binary fission became sporoblasts. Two types
      of spores were recognized, both uninucleate, i.e., ovoid or slightly ovoid
      microspores with a mean size of 5.1 x 2.2 microm and much less frequent as
      elongated oval macrospores with a mean size of 8.9 x 3.1 microm. The polar tube
      has between 12 and 14 coils arranged in 1, 2, or 3 layers. Taken together, these
      characteristics suggest that this microsporidian infecting V. conspersa is a new
      species of Glugea, which we have named Glugea vincentiae.

PMID- 15856892
TI  - The effect of amphotericin b derivatives on Leishmania and immune functions.
AB  - The effects of a water-soluble amphotericin B (AmB)-arabinogalactan (AG)
      conjugate on several immune functions were investigated. The experiments measured
      the effects of AmB-AG on (1) release of tumor necrosis factor-alpha (TNF-alpha),
      nitric oxide (NO), and interferon-gamma (IFN-gamma) from phagocytic cells and (2)
      cell-mediated immune responses. AmB-AG increased TNF-alpha release from mouse
      peritoneal macrophages and human monocytes but had no effect on IFN-gamma and NO
      release. A commercial preparation of nonconjugated AmB (Fungizone) also increased
      TNF-alpha production, but to a lesser extent than AmB-AG. AG alone had no effect
      on TNF-alpha production, proving that AmB caused the increased TNF-alpha
      production. AmB-AG and Fungizone were also tested for their effect on B- and T
      cell proliferation. Neither compound altered T-lymphocyte responses to
      concanavalin A, but both inhibited the stimulation of B lymphocytes by
      lipopolysaccharides. However, Fungizone showed a stronger inhibitory effect on B
      cells. Allocytotoxicity was also inhibited by AmB-AG and more strongly by
      Fungizone. The increased production of TNF-alpha by cells treated with AmB-AG and
      the lower inhibitory effect of AmB-AG on lymphocyte stimulation and
      allocytotoxicity, as compared with Fungizone, explain the better therapeutic
      efficacy of the AmB-polysaccharide conjugate. AmB is active because of its
      preferential binding to ergosterol rather than cholesterol, the former sterol
      preferentially present in parasite surface membranes. This is also valid for the
      axenic amastigotes, which were sensitive to the AmB-AG. Overall, our results
      suggest that the antileishmanial activity of AmB-AG is mediated both directly and
      via modulation of immune functions.

PMID- 15856893
TI  - Serological investigation of Theileria sergenti using latex agglutination test in
      South Korea.
AB  - Theileria sergenti causes persistent theileriosis in cattle, characterized by
      fever and chronic anemia. Theileriosis causes losses in feed efficiency and
      growth retardation through cycling infections in endemic areas. Among several
      major proteins of T. sergenti merozoites, the surface protein p33 is reported to
      be the most immunogenic. In this study, we investigated the use of p33 as a
      diagnostic antigen in a latex agglutination test to monitor antibodies against T.
      sergenti. When compared with TaqMan polymerase chain reaction, the sensitivity
      and specificity of the latex agglutination test were 86.5 and 92.5%,
      respectively. An epidemiological survey using the latex agglutination test was
      conducted with 1,046 sera collected from 4 slaughterhouses and 2 individual
      pasture farms throughout South Korea; 27.3% of samples were seropositive,
      depending on the areas in which the cattle were raised. This study indicated that
      the latex agglutination test could be used as a convenient tool for
      epidemiological monitoring of T. sergenti infections in the field.

PMID- 15856894
TI  - The trypanocidal effect of sesquiterpene lactones helenalin and mexicanin on
      cultured epimastigotes.
AB  - Sesquiterpene lactones constitute a large group of biologically active compounds
      obtained from plants. The lactones, mexicanin (MXN) and helenalin (HLN), were
      reported recently as active against the infective form of Trypanosoma cruzi. In
      this work, we studied the effects of these compounds on the growth and viability
      of the noninfective epimastigote, to compare the sensitivity of the 2 stages and
      to characterize their actions. Both compounds were cytotoxic to the parasites,
      with HLN (inhibitory concentration 50% [IC50] 1.9 +/- 0.08 microM) more potent
      than MXN (IC50 3.8 +/- 0.19 microM) and the typanocidal drug, benznidazole (IC50
      8.6 +/- 2.5 microM). The results showed that epimastigotes are less sensitive
      than trypomastigotes to the compounds. The trypanocidal effect of these lactones,
      irreversible after 12-hr exposure, was not reversed by the reducing agents
      dithiotreitol or beta-mercaptoethanol. Ultrastructurally, we observed cytoplasmic
      vacuolization and nuclear disorganization. Although concentrations between 0.5
      and 1.5 microM of the drugs were not lethal to the parasites, epimastigotes
      became thinner and their nuclei became more pycnotic after exposure. We conclude
      that MXN and HLN are deleterious for T. cruzi epimastigotes and that their
      mechanism of action is different than that of the related lactone,
      dehydroleucodine.

PMID- 15856895
TI  - Artemether as adjuvant therapy to praziquantel in murine Egyptian schistosomiasis
      mansoni.
AB  - We investigated the activity of artemether (ART) against different developmental
      stages of schistosomes alone and in addition to praziquantel (PZQ). ART was
      administered orally (400 mg/kg) 4 and 6 wk postinfection (PI), 4 and 5 wk PI, or
      4 or 6 wk PI alone and in addition to oral PZQ (500 x 2 mg/kg) 6 wk PI. Mice were
      killed in parallel to infected untreated controls 8 wk PI. Parasitological
      parameters and histological changes in the liver were studied. ART given 4 and 6
      wk PI reduced worm burdens by 59 and 55% and tissue egg load by 96 and 90%,
      respectively. Moreover, eggs in different developmental stages were not found.
      The reduction in worm and egg burden (63 and 58%, and 96 and 99%, respectively)
      in mice treated with ART 4 and 5 wk or 4 and 6 wk PI was comparable with that in
      ART-treated mice at 4 or 6 wk PI. Compared with PZQ alone, combined treatment of
      PZQ and ART (4 and 5 wk or 4 and 6 wk PI) did not enhance worm eradication, but
      there was a complete absence of parasite eggs. Livers revealed no granulomata
      when ART was given 4 and 5 wk or 4 and 6 wk PI, with minimal central necrosis in
      those treated 4 and 6 wk PI. In conclusion, combined treatment of ART (4 and 6 wk
      PI) and PZQ resulted in >90% worm eradication and amelioration of Schistosoma
      mansoni eggs from the tissues, with minor histological changes in the liver.

PMID- 15856896
TI  - Zoonotic genotype of Giardia intestinalis detected in a ferret.
AB  - Giardia intestinalis has been found in a variety of mammals, including humans,
      and consists of host-specific and zoonotic genotypes. There has been only 1 study
      of G. intestinalis infection in weasels, but the genotype of its isolate remains
      unclear. In this study, we report the isolation of Giardia in a ferret exhibited
      at a pet shop. The isolate was analyzed genetically to validate the possibility
      of zoonotic transmission. Giardia diagnostic fragments of the small subunit
      ribosomal RNA, beta-giardin, and glutamate dehydrogenase genes were amplified
      from the ferret isolate and sequenced to reveal the phylogenetic relationships
      between it and other Giardia species or genotypes of G. intestinalis reported
      previously. The results showed that the ferret isolate represented the genetic
      group A-I in assemblage A, which could be a causative agent of human giardiasis.

PMID- 15856897
TI  - Absence of vacuolar membrane involving Toxoplasma gondii during its intranuclear
      localization.
AB  - Tachyzoites of Toxoplasma gondii were located inside the nucleus of both skeletal
      muscle cells infected in vitro and peritoneal exudate cells collected from
      infected mouse in vivo. Ultrastructural analysis demonstrated that T. gondii
      invades the nucleus of host cells by the parasite apical region and with
      constriction of its body. We noted that the rhoptry, a secretory organelle of the
      parasite that is involved in the host cell invasion mechanism, was empty in the
      intranuclear T. gondii. The parasites were found in the nuclear matrix without
      evidence of the vacuolar membrane. Frequently, new parasites invaded host cell
      nucleus, which was already infected. The significance of this nuclear invasion
      could reflect an alternative route of T. gondii for its transitory survival or an
      escape mechanism from the host immune response during the in vivo infection (or
      both).

PMID- 15856898
TI  - Parasitic helminths of Eurasian collared-doves (Streptopelia decaocto) from
      Florida.
AB  - Sixty-three Eurasian collared-doves (ECDs) (Streptopelia decaocto) from Florida
      were examined for parasitic helminths from June to December 2001. Nine species of
      helminths were identified (5 nematodes, 2 cestodes, and 2 trematodes). The most
      prevalent helminths were Ascaridia columbae (73.0%), Fuhrmannetta crassula
      (28.6%), Ornithostrongylus quadriradiatus (12.7%), and Bruscapillaria obsignata
      (11.1%). The helminths with the greatest mean intensity were Tanaisia bragai
      (13.5), A. columbae (9.3), and O. quadriradiatus (7.1). In Florida, the mean
      intensity of A. columbae in ECDs (9.3) was similar to that found in white-winged
      doves (Zenaida asiatica) (9.1) (P = 0.461), and both the intensities were
      significantly higher than that in the native mourning doves (Zenaida macroura)
      (3.7) (P = 0.001 and 0.005, respectively). Fuhrmannetta crassula is reported for
      the first time in columbids from Florida.

PMID- 15856899
TI  - Clinical muscular sarcocystosis in a dog.
AB  - Muscular sarcocystosis is a rare infection in dogs. Clinical myositis associated
      with an unidentified species of Sarcocystis was diagnosed in an adult dog from
      Canada. There was granulomatous myositis associated with numerous immature
      sarcocysts in a muscle biopsy obtained from the dog. The sarcocysts were up to
      550 microm long and up to 45 microm wide. The sarcocyst wall was approximately 1
      microm thick and contained short, stubby, villar protrusions that lacked
      microtubules. This is the first report on clinical muscular sarcocystosis in a
      dog.

PMID- 15856900
TI  - Detection of antibodies to Neospora caninum in cattle by enzyme-linked
      immunosorbent assay with truncated NcSRS2 expressed in Escherichia coli.
AB  - The surface antigen 1-related sequence 2 of Neospora caninum (NcSRS2) is
      considered as an immunodominant antigen. In this study, the gene encoding
      truncated NcSRS2 (NcSRS2t) lacking an N-terminal signal peptide and C-terminal
      hydrophobic regions was expressed in Escherichia coli, and its diagnostic
      potential in an enzyme-linked immunosorbent assay (ELISA) was evaluated. ELISA
      could discriminate clearly between known N. caninum-positive and -negative sera
      from cattle. Field serum samples collected from cattle in Brazil were examined
      for the diagnosis of N. caninum infection using ELISA. Of the 197 samples
      analyzed, 64 (32.5%) samples were positive for antibodies to N. caninum. Of the
      64 ELISA-positive samples, 58 (90.6%) were confirmed as positive by Western blot
      analysis with whole-parasite antigens. These results suggest that ELISA with
      recombinant NcSRS2t is an effective method for diagnosis of N. caninum infection
      in cattle.

PMID- 15856901
TI  - Effects of alpha- and beta-adrenergic agonists on Toxoplasma gondii infection in
      murine macrophages.
AB  - We investigated the effects of alpha- and beta-adrenergic receptor agonists on
      the ability of Toxoplasma gondii to infect and proliferate in cultured murine
      macrophages. Macrophages pretreated in vitro with varying concentrations of alpha
      and beta-adrenergic agonists and incubated with the RH strain of T. gondii did
      not result in a significant increase in the percentage of infected macrophages
      compared with negative controls. When parasites were pretreated with L
      phenylephrine, an alpha-agonist, and L-isoproterenol, a beta-agonist, before
      infection, there was no significant change in the percentage of infected
      macrophages. Clonidine, an alpha2-adrenergic agonist, led to a significant
      decrease in the number of infected macrophages at all concentrations tested. The
      effects of clonidine were blocked by yohimbine, a specific alpha2-adrenergic
      antagonist, but not by phentolamine, an alpha1-adrenergic antagonist. These
      results suggest that the antiparasitic effects exhibited by clonidine (alpha2
      adrenergic agonist) are mediated through an alpha2-adrenoreceptor found on the
      surface of T. gondii.

PMID- 15856902
TI  - Detection of Paragonimus heterotremus eggs in experimentally infected cats by a
      polymerase chain reaction-based method.
AB  - A polymerase chain reaction (PCR) procedure for the detection of Paragonimus
      heterotremus eggs in stool samples was developed and compared with Stoll's egg
      count method. The primers were designed on the basis of a previously constructed
      pPH-13-specific DNA probe, which produced an approximate 0.5-kb amplified
      product. This PCR method could detect as few as 5 eggs in 0.6 g of artificially
      inoculated feces of a healthy control cat or as little as 1 x 10(-4) ng of P.
      heterotremus genomic DNA. The assay had 100% sensitivity in all infected cats.
      The method did not yield an approximate 0.5-kb product with DNA from other
      parasites such as Gnathostoma spinigerum, Trichinella spiralis, Fasciola
      gigantica, Echinostoma malayanum, Opisthorchis viverrini, Dirofilaria immitis,
      and Taenia saginata; exceptions were Paragonimus siamensis and Paragonimus
      westermani. In addition, no genomic DNA from Escherichia coli, Burkholderia
      pseudomallei, Acinetobacter anitratus, Mycobacterium tuberculosis, Staphylococcus
      aureus, beta-Streptococcus grA, and Proteus mirabilis or from the vertebrate and
      invertebrate hosts of P. heterotremus was amplified in the PCR assay. This assay
      has great potential for application in clinical epidemiological studies.

PMID- 15856903
TI  - Disseminated visceral coccidiosis and cloacal cryptosporidiosis in a Japanese
      white-naped crane (Grus vipio).
AB  - A 4-mo-old male Japanese white-naped crane (Grus vipio) kept in an outdoor
      exhibit at the Everland Zoological Gardens in Korea became depressed and
      developed anorexia, weight loss, and diarrhea. Death of this bird was associated
      with an overwhelming systemic infection by an intracellular coccidian parasite,
      which resulted in necrosis and granulomatous inflammation in a number of major
      organs, including the intestine, liver, spleen, and kidney. Coccidian parasite
      laden macrophages were commonly found in the blood vessels of these organs. Using
      electron microscopy and polymerase chain reaction assays, the parasite was
      identified as Eimeria sp. The bird was also infected with Cryptosporidium sp.,
      which suggests an immunosuppressed state, although the cause of such suppression
      was not identified. Our findings suggest that an initial Eimeria sp. intestinal
      infection spread to other organs through the blood vessels, with the
      immunosuppressed state possibly contributing to a rapid hematogenous
      transmission. To our knowledge, this is the first report of disseminated visceral
      coccidiosis caused by Eimeria sp. in a captive Japanese white-naped crane.

PMID- 15856904
TI  - Significant morphological but little molecular differences between Trypanosoma of
      rodents from Alaska.
AB  - We examined blood smears of 173 rodents and 33 shrews captured at 4 sites in the
      Gates of the Arctic National Park, northern Alaska, in summer 2002. Trypanosoma
      spp. were detected in the plasma of 5 Microtus oeconomus, 4 Microtus miurus, and
      1 Lemmus trimucronatus. The trypomastigote morphology from different individuals
      of M. oeconomus caught at the same site and of M. miurus from different sites
      varied significantly. The 4 DNA sequences obtained from the blood smear positive
      samples contained 2 different haplotypes very similar to each other and to that
      of Trypanosoma microti. Of possible vectors of blood parasites, the flea
      Amalaraeus dissimilis was collected from M. miurus.

PMID- 15856905
TI  - Genotyping of Giardia duodenalis from humans and dogs from Mexico using a beta
      giardin nested polymerase chain reaction assay.
AB  - Cysts of Giardia duodenalis were collected in Mexico from symptomatic children (n
      = 9) and from pet dogs (n = 5), and they were directly characterized by nested
      polymerase chain reaction (PCR) amplification of the beta-giardin gene. Eight
      isolates of human origin established as in vitro cultures and 2 reference
      strains, representing assemblages A and B of G. duodenalis, were also analyzed.
      PCR-restriction fragment length polymorphism showed that all isolates belonged to
      assemblage A. Sequence analyses indicated that the large majority of isolates
      were of the A1 genotype; interestingly, 2 human isolates displayed the A3
      genotype, which has been previously identified in human isolates from Italy. The
      presence of cysts of the A1 and A3 genotypes in isolates from pet dogs is
      consistent with their role as reservoirs for human infection, although further
      studies are needed to confirm the occurrence of zoonotic transmission.
      Remarkably, cysts of assemblage B have not been found in any of the Mexican
      isolates studied to date.

PMID- 15856906
TI  - Functional expression of a recombinant copper/zinc superoxide dismutase of
      filarial nematode, Brugia malayi.
AB  - A gene encoding a copper/zinc superoxide dismutase (Cu/ Zn-SOD) of a filarial
      nematode, Brugia malayi, has been isolated and the biochemical properties of a
      functionally expressed recombinant enzyme were investigated. The cloned
      complementary DNA contained a single open reading frame of 477 bp encoding 158
      amino acids (aa), which conserved metal-binding residues as well as residues
      specific for Cu/Zn-SODs. Comparison of the deduced aa sequence of the enzyme with
      that of other helminthes species, including filarial worms, exhibited high degree
      of similarities (49-98%). Recombinant enzyme of 32 kDa had an isoelectric point
      of 6.6 and was shown to consist of 2 subunits linked by interchain disulfide
      bonds. Enzyme activity of the recombinant protein was inhibited by potassium
      cyanide and hydrogen peroxide but not by sodium azide. It showed a wide range of
      pH optima, i.e., 7.0-11.0 and was highly resistant to heat inactivation.

PMID- 15856907
TI  - Modified sugar centrifugal flotation technique for recovering Echinococcus
      multilocularis eggs from soil.
AB  - Among soil-transmitted parasitic diseases, alveolar hydatidosis due to the
      ingestion of Echinococcus multilocularis eggs is becoming a serious problem in
      Hokkaido, the northern most island of Japan. Dissemination of the infection far
      from the endemic areas can occur if motor vehicles transmit soil contaminated
      with eggs. No appropriate and validated method for recovering the taeniid eggs
      from soil is available. A modified sugar centrifugal flotation technique, using a
      sucrose solution of specific gravity 1.27 and 0.05% Tween-80, was evaluated as a
      method to successfully recover eggs from soil. Contamination levels as low as 10
      eggs per gram could be detected. This method may be useful to determine the
      prevalence of E. multilocularis, its transmission, and the potential for by
      monitoring soil contamination with eggs.

PMID- 15856908
TI  - Spatial variation of Trichinella prevalence in rats in Finnish waste disposal
      sites.
AB  - Trichinellosis is 1 of the most widespread parasitic zoonoses in the world and
      can be lethal to humans. Trichinella spp. are also parasites of considerable
      economic importance. Because rats may play a role in the transmission of
      trichinellosis to swine and farmed wild boar, 767 brown rats (Rattus norvegicus
      Berkenhout) from 13 Finnish waste disposal sites were examined for Trichinella
      spp. by a HCl-pepsin digestion method. Trichinella spp. were found to be a common
      parasite in trapped rats (overall prevalence, 19%) detected in 12 of 13 dumps.
      Significant differences were observed between sites in the prevalence (0-49%) of
      Trichinella spp. Female rats were more often and more heavily infected than
      males, but age was not shown to be a risk factor for trichinellosis. In addition,
      positive correlation was demonstrated between rat population density and
      prevalence. Trichinella spiralis was identified by multiplex polymerase chain
      reaction in 28 rats. The median density of infection was 42 (range, 0.5-6,925)
      larvae/ g of host tissue, but neither the occurrence nor the density of the
      parasite was related to the physical condition of the animal.

PMID- 15856909
TI  - Helminths of the Virginia opossum Didelphis virginiana (Mammalia: Didelphidae) in
      Mexico.
AB  - The goal of this study was to provide further information about helminth
      parasites of Virginia opossum Didelphis virginiana Kerr, 1792 from Mexico. During
      routine faunal investigations between 1958 and 2001, 101 opossum were necropsied.
      Nineteen taxa of helminths were collected, representing 13 genera from hosts in
      27 localities from Mexico. There are 58 new locality records, with 6 species
      recorded in Mexico for the first time: Brachylaima virginiana Dickerson, 1930;
      Cruzia americana Mapleston, 1930; Didelphonema longispiculata (Hill, 1939);
      Didelphostrongylus hayesi Prestwood, 1976; Viannaia didelphis Travassos, 1914;
      and Viannaia viannai Travassos, 1914. This increases the number of helminth taxa
      previously known for this host in Mexico to 28.

PMID- 15856910
TI  - Effects of heparin administration on Trypanosoma brucei gambiense infection in
      rats.
AB  - We examined whether heparin administration influences in vivo trypanosome
      proliferation in infected rats. Administration of heparin every 8 hr via cardiac
      catheter inhibited growth of Trypanosoma brucei gambiense and prolonged survival
      of treated rats. Heparin administration increased lipoprotein lipase activity,
      high-density lipoprotein (HDL) concentration in the blood, and haptoglobin
      messenger RNA content of the liver. The presence of heparin in culture media did
      not directly affect proliferation of trypanosomes in vitro. However, the addition
      of plasma from infected rats treated with heparin to culture media decreased the
      number of trypanosomes. This effect was decreased by incubating the trypanosomes
      with benzyl alcohol, a known inhibitor of receptor-mediated endocytosis of
      lipoprotein. These data suggested that heparin administration reduced the number
      of trypanosomes in infected rats. Trypanosome lytic factor, a HDL and haptoglobin
      related protein, protects humans and some animals from infection by Trypanosoma
      brucei brucei. In rats, increases in HDL and haptoglobin may affect the
      proliferation of T. b. gambiense.

PMID- 15856911
TI  - Development of Neospora caninum cultured with human serum in vitro and in vivo.
AB  - Because there has been no report of symptomatic Neospora caninum infection in
      humans, we examined the effect of human serum on the parasite's growth in either
      a bovine angioendothelial cell or Caco-2 cell culture in vitro and in
      immunocompromised mice in vivo. There was no difference in intracellular parasite
      numbers between cells incubated with human serum at 24 hr after challenge and
      those incubated with fetal bovine serum (FBS), which has no titer for the anti-N.
      caninum agglutination antibody test. Serum of sheep infected with N. caninum,
      which has the anti-N. caninum antibody, reduced the numbers of the intracellular
      parasite significantly. We also showed that there was no inhibitory effect on the
      intracellular multiplication of the parasite in cells incubated with human serum
      through incorporation of 3H-uracil. CB-17 scid mice administered human serum
      daily and challenged with N. caninum died on day 20 or 22 after challenge, when
      large numbers of parasite clusters were found in the brain, oviduct, adrenal
      gland, lung, stomach, spleen, skeletal muscle, pancreas, and mesenteric lymph
      nodes. Scid mice administered FBS survived until the end of the experiment. These
      results suggest that adult human serum may have no inhibitory effect on the
      development of N. caninum in vitro and in vivo.

PMID- 15856912
TI  - Late cutaneous metastases in C3H SCID mice infected with Leishmania amazonensis.
AB  - The biological behavior of Leishmania amazonensis in the mammalian host is highly
      variable, resulting in local to diffuse cutaneous lesions that sometimes
      metastasize. Inflammation and, more specifically, CD4+ T cells have been shown to
      enhance metastases in mice infected with L. amazonensis, suggesting that the
      process may be lymphocyte mediated. However, we document, in this study, the
      development of multiple cutaneous metastases in C3H SCID mice infected with L.
      amazonensis. This shows that functional T and B cells are not required for
      metastases to occur.

PMID- 15856913
TI  - An ectosymbiotic flatworm, Temnocephala chilensis, as second intermediate host
      for Echinoparyphium megacirrus (Digenea: Echinostomatidae) in Patagonia
      (Argentina).
AB  - During a survey of parasites of the Patagonian freshwater crab Aegla neuquensis
      neuquensis, its ectosymbiont Temnocephala chilensis was found parasitized with an
      echinostomatid metacercaria with 43 collar spines. Of the 414 T. chilensis
      collected, 106 were parasitized with metacercariae of Echinoparyphium sp.
      Ovigerous adults of E. megacirrus were obtained from domestic chicks
      experimentally infected with metacercariae obtained from temnocephalans. This is
      the first record of temnocephalans being parasitized by digeneans.

PMID- 15856914
TI  - Succinate enhances the cyclic guanosine monophosphate-altered intestinal motility
      in the rat.

PMID- 15856915
TI  - People with disabilities: how are we going to meet their needs?
AB  - The proportion of the population age 65+ years will increase to 20% of U.S.
      residents in the next decades. It has been shown that the portion of the
      population with disabilities increases with age. Providing care for individuals
      with disabilities is expensive and consuming an increasing component of health
      service benefits. Health providers increasingly will be called upon to provide
      services for millions of persons with a wide range of ages and disabilities. How
      well prepared will the health professions, the individual practitioners,
      including dentists, and society in general be to meet these increasing needs?

PMID- 15856916
TI  - Caries incidence and increments in Adelaide nursing home residents.
AB  - The objective of The Adelaide Dental Study of Nursing Homes was to quantify
      coronal and root caries incidence and increments in residents of Adelaide nursing
      homes. A longitudinal design was used to conduct dental inspections, completed by
      calibrated dental examiners, for residents of 7 randomly selected nursing homes
      at both baseline and at one-year follow-up. The nursing home residents in this
      study were very functionally dependent, medically compromised, cognitively
      impaired and behaviorally difficult older adults. The coronal caries surface
      incidence was 64.4% and root caries surface incidence was 48.5%. There were 72.1%
      of residents who had coronal and/or root caries increments between baseline and
      one-year. The coronal and root caries increments in these residents were high
      (adjusted caries increment = 2.5 coronal and 1.0 root surfaces), and were many
      times greater than that reported from a longitudinal study of community-dwelling
      older adults in Adelaide. Residents with eating and nutritional problems
      developed high levels of new caries. Both coronal and root caries incidence and
      increments were high in these nursing home residents over the one-year follow-up
      period.

PMID- 15856917
TI  - Coronal and root caries in the older Iowans: 9- to 11-year incidence.
AB  - This study reports on coronal and root caries incidence in elderly Iowans between
      1987 and 1998. The sample consisted of 74 survivors of the Iowa 65+ Oral Health
      Study cohort who received oral examinations both in 1987 and between 1996-98. The
      study found that average untreated coronal and root increments were 0.96 and 0.69
      surfaces, filled increments were 18.22 and 1.28 surfaces, and combined increments
      were 18.3 and 1.27 surfaces, respectively. Therefore, annualized untreated
      coronal and root increments were 0.10 and 0.07 surfaces, filled were 1.80 and
      0.13 surfaces, and combined increments were 1.81 and 0.12 surfaces, respectively.
      The annualized attack rates were 2.13 for coronal and 0.80 for root caries.
      Approximately 93% of the subjects developed some new coronal and 43% some new
      root caries increment. Dental caries still constitute a significant problem since
      a large proportion of the elderly developed caries during this period. This
      suggests a need for improved preventive and treatment strategies for this aged
      population.

PMID- 15856918
TI  - Nursing home executive directors' perception of oral care in long-term care
      facilities.
AB  - Oral health in long-term care (LTC) facilities has been repeatedly documented as
      less than ideal. The complex nature of this environment has made it difficult to
      understand and improve the oral health status of residents through education and
      training. The purpose of the study was to investigate how the executive directors
      (EDs) of LTC facilities value oral health and to determine facility variables,
      which may influence how oral care is delivered. A mail survey of the EDs of all
      LTC facilities in Ohio (n = 1018) was conducted with 338 responses received after
      secondary follow-up (33.2% response rate). The 30-item survey included
      information concerning the nursing facility, the EDs, the EDs' perception of the
      level of oral health care, and value statements rated on a Likert-like scale. The
      results of the survey showed that more than two-thirds of the EDs were female and
      that most facilities were proprietary (70.3%). ED gender was not statistically
      associated with any of the oral health variables. Fifty-three percent of the EDs
      rated their residents' oral health as fair or poor but were still satisfied with
      the oral care provided at their facilities. The apparent discontinuity between
      perceived levels of oral health and satisfaction with oral care suggests that EDs
      are distanced from the oral care of their residents or they do not acknowledge
      oral health care needs. While the survey results revealed important facility
      characteristics and administrators' perceptions about oral health, the most
      important aspect of this project was the low response rate despite secondary
      follow-up. That, coupled with the negativity expressed upon follow-up, suggests a
      larger issue that may affect oral health in nursing facilities: oral health
      continues to have a low priority in this setting. Continuing efforts to improve
      oral health and educate LTC professionals about oral health's influence on
      general health is critical for managing the oral health of future generations of
      aging adults.

PMID- 15856919
TI  - Effect of 2% plain and fluoridated milk on root surface caries in vitro.
AB  - The caries-protective effect of milk and fluoridated milk on enamel has been
      reported; however, few data are available concerning the role of milk and/or
      fluoridated milk on root surfaces. The aim of this study was to compare the
      effect of plain and fluoridated milk on root surface caries. Artificial root
      surface lesions were created, sectioned and analyzed using polarized light
      microscopy (PLM) and microradiography (MRG). The sections were covered except for
      the original surface and assigned to a treatment group. The samples were immersed
      in 2% plain milk or fluoridated milk for 40 hours and re-evaluated. Changes were
      measured and mean differences were compared with an unpaired t-test. Both
      techniques revealed a reduction in lesion depth for each milk group; however, a
      significantly greater reduction (p<0.05) was observed with the fluoridated milk.
      These results suggest that fluoridated milk may have a beneficial effect on the
      remineralization of root surface caries.

PMID- 15856920
TI  - Patients with oropharyngeal cancer: a comparison of adults living independently
      and patients living in long-term care facilities.
AB  - The low survival rate of persons with oropharyngeal cancer (OPC) is directly
      related to the size of the primary tumor, lymph node involvement and to the
      smoking history. The association between medical independence and the survival
      rate of oral cancer is unclear. The purpose of this study was to assess the
      survival rate of institutionalized patients with oral cancer compared to those
      living independently. Information regarding gender, age, tobacco habits, disease
      characteristics, and survival status were recorded and statistically analyzed
      from 30 patients with oral cancer who were institutionalized compared to 543
      patients with oral cancer who were non-institutionalized. Patients living in long
      term care facilities (LTC) were significantly older than the independent patients
      (67% were 70 years or older versus 28% of independent patients) (p = 0.0001). No
      differences in smoking habits were noted between the two groups but more patients
      who were institutionalized stopped smoking at the time of diagnosis (p = 0.47).
      More patients who were institutionalized were diagnosed with positive lymph node
      involvement (p = 0.09). Significantly higher all-cause and disease-free 5-year
      survival rates were noted in the patients living independently, compared to the
      adults who were institutionalized (32% and 60% compared to 7% and 26%
      respectively; p < 0.05). The disease-specific 5-year survival was directly
      related to age (p = 0.001), size of the tumor (p = 0.001), and lymph node
      involvement (p < 0.001). Significant longer survival rates were observed for
      patients living independently. The more advanced disease seen in the patients who
      were institutionalized may be due to a delay in diagnosis, which may be
      associated with fewer symptoms, limited report of symptoms, a lack of attention
      or a misdiagnosis of the oral lesion.

PMID- 15856922
TI  - Our roots in nursing: advocacy and activism.

PMID- 15856923
TI  - Alcohol or drug addiction and the circle of control.

PMID- 15856924
TI  - Respect.

PMID- 15856925
TI  - Behind the scenes, surgical unit treats Fallujah's casualties.

PMID- 15856926
TI  - Depression in elderly populations.

PMID- 15856927
TI  - Assisted living and RN practice.

PMID- 15856929
TI  - My blizzard baby.

PMID- 15856930
TI  - ASNA independent study activity: "Selective serotoni inhibitors (SSRIs)--what
      nurses should know".

PMID- 15856931
TI  - In appreciation of Jacob Beck.

PMID- 15856932
TI  - Jacob Beck--reminiscence and appreciation.

PMID- 15856933
TI  - Observations on associative grouping (in honor of Jacob Beck).
AB  - Beck (1972) pointed out that grouping tasks, where one set of elements is
      distinguished from another, do not imply associative links within either set of
      elements but could rely on processes of segregation. Although many physiological
      theories of grouping are purely associative there are not many methods of
      isolating associative processes psychophysically. One method has been to measure
      common resolutions of elements when they are presented under conditions of depth
      and motion ambiguity. In the present paper a number of the issues surrounding
      grouping are considered, particularly in relation to associative processes. These
      include whether grouping is post-constancy and post-completion, grouping with and
      without emergent features, the role of top-down processing and attention and the
      explanatory role of general principles such as simplicity and likelihood.

PMID- 15856934
TI  - Anisotropies in peripheral vernier acuity.
AB  - Vernier acuity for short horizontal, vertical and oblique target lines was
      measured in many locations in the periphery of the visual field in normal human
      observers. In the 10 deg periphery, the average alignment threshold with oblique
      vernier lines in eight locations for three observers was 2.29 times higher than
      that with vertical and horizontal target lines. This oblique effect was found
      everywhere in the visual field. Similar conclusions are drawn for configurations
      in which the lines were replaced by just their distal endpoints, but here,
      additionally, performance was distinctly better when the dot pair was collinear
      with the fixation point, i.e. oriented radially, than when it was oriented
      tangentially. Both for vernier lines and for dot pairs, in all observers,
      horizontal configurations showed somewhat better thresholds than vertical ones.
      These results suggest an inherent pattern of connectivity throughout the visual
      field favoring processing in the cardinal orientations over the obliques, the
      radial over the tangential and, to a limited extent, the horizontal over the
      vertical.

PMID- 15856935
TI  - Interactions between pattern and color in the visual system: temporal aspects of
      the McCollough effect.
AB  - The perception of the color of a surface can be influenced by many factors
      including its material properties and the composition of the illuminant.
      McCollough demonstrated that sensory conditioning could also influence the
      perception of surface color by inducing a long-lasting pattern specific color
      aftereffect. This effect has been extensively studied since its original report
      and a number of increasingly complex explanations have been proposed. In this
      article I examine the temporal properties of a simple learning model of the
      McCollough effect (ME). This model has previously been used to account for
      quantitative data sets obtained from a series of monocular and binocular variants
      of the ME. The model replicates the acquisition and decay of the ME, pre- and
      post-induction interference effects, and can also simulate the effects of various
      cholinergic and anticholinergic drugs that have been shown to influence ME
      induction and decay.

PMID- 15856936
TI  - The role of the Gestalt principle of similarity in the watercolor illusion.
AB  - The watercolor illusion presents two main effects: a long-range assimilative
      color spreading (coloration effect), and properties imparting a strong figure
      status (figural effect) to a region delimited by a dark (e.g. purple) contour
      flanked by a lighter chromatic contour (e.g. orange). In four experiments, the
      strength of the watercolor illusion to determine figure-ground organization is
      directly compared (combined or pitted against) with the Gestalt principle of
      similarity both of color and line width. The results demonstrated that (i) the
      watercolor illusion and, particularly, its figural effect won over the classical
      Gestalt factors of similarity; (ii) the watercolor illusion cannot be due to the
      coloration effect as suggested by the similarity principle; (iii) coloration and
      figural effects may be independent in the watercolor illusion, and (iv) the
      watercolor illusion can be considered as a principle of figure-ground segregation
      on its own. Two parallel and independent processes as proposed within the FACADE
      model (Grossberg, 1994, 1997) are suggested to account for the two effects of
      coloration and figural enhancement in the watercolor illusion.

PMID- 15856937
TI  - Element-arrangement textures in multiple objective tasks.
AB  - In his long years of studying visual perception, Jacob Beck made many
      contributions. This article is a short review of one line of his research--that
      we shared in--and then a presentation of some results from on-going research down
      the same line. In the 1980s Beck and his colleagues introduced a new kind of
      visual stimulus: element-arrangement texture patterns. A series of studies with
      these patterns has shown that a model containing spatial-frequency and
      orientation-selective channels can explain many aspects of texture perception as
      long as two kinds of nonlinear processes are also included; the published studies
      are briefly summarized. The new results come from multiple objective tasks
      requiring the observer to make simple discriminations between second-order
      element-arrangement textures. Results with the objective tasks replicate
      previously published results using subjective ratings, and the use of the
      objective tasks allows us to explore several more fine-grained questions about
      complex (second-order) channels and normalization.

PMID- 15856938
TI  - Neural mechanisms of human texture processing: texture boundary detection and
      visual search.
AB  - Texture of various appearances, geometric distortions, spatial frequency content
      and densities is utilized by the human visual system to segregate items from
      background and to enable recognition of complex geometric forms. For automatic,
      or pre-attentive, segmentation of a visual scene, sophisticated analysis and
      comparison of surface properties over wide areas of the visual field are
      required. We investigated the neural substrate underlying human texture
      processing, particularly the computational mechanisms of texture boundary
      detection. We present a neural network model which uses as building blocks model
      cortical areas that are bi-directionally linked to implement cycles of
      feedforward and feedback interaction for signal detection, hypothesis generation
      and testing within the infero-temporal pathway of form processing. In the spirit
      of Jake Beck's early investigations our model particularly builds upon two key
      hypotheses, namely that (i) texture segregation is based on boundary detection,
      rather than clustering homogeneous items, and (ii) texture boundaries are
      detected mainly on the basis of larger scenic contexts mediated by higher
      cortical areas, such as area V4. The latter constraint provides a basis for
      element grouping in accordance to the Gestalt laws of similarity and good
      continuation. It is shown through simulations that the model integrates a variety
      of psychophysical findings on texture processing and provides a link to the
      underlying physiology. The functional role of feedback processing is demonstrated
      by context dependent modulation of V1 cell activation, leading to sharply
      localized detection of texture boundaries. It furthermore explains why pre
      attentive processing in visual search tasks can be directly linked to texture
      boundary processing as revealed by recent EEG studies on visual search.

PMID- 15856939
TI  - Effects of ISI and flash duration on the identification of briefly flashed
      stimuli.
AB  - The identification accuracy of briefly flashed stimuli followed by an
      interstimulus interval (ISI) of variable length was compared to that obtained
      with longer flashes that prolonged the exposure of the stimulus throughout the
      ISI. The interval between the onset of the stimulus and the onset of the mask
      (stimulus onset asynchrony (SOA)) was the same in the two conditions. Consistent
      with a dependence of visual identification on SOA, the percentages of correct
      identification in the two conditions were approximately similar at all SOAs
      irrespective of the level of noise, stimulus familiarity, and stimulus
      complexity. However, departures from the onset-onset rule were also present.
      While the two conditions yielded virtually identical identification accuracy with
      an SOA of 80 ms, small but significant differences were found for shorter and
      longer intervals. Possible theoretical explanations of the results are presented.

PMID- 15856940
TI  - [RNA polymerase III transcription apparatus: structure and transcription
      regulation].
AB  - RNA polymerase III is a complex multi-subunit enzyme directing transcription of
      small stable non-translated RNA genes: tRNAs, 5S rRNA, Alu-RNA, U6 snRNA genes
      and some others (class III genes). Because of its complexity the enzyme is the
      worst studied among three forms of eukariotic RNA polymerases, but it draws more
      attention of the researchers in recent years. The reason is that new data
      appeared about an essential role of RNA polymerase III RNA products in such
      important cell processes as growth, proliferation and differentiation. It was
      shown that the RNA product levels are changed depending on cell growth rate and
      cell cycle stage, during cancer transformation, virus infection and heat shock,
      and either depend on physiological state of the cell (slow and active
      proliferation and apoptosis). In this review we consider the structure and
      function of RNA polymerase III, its general transcription factors and holoenzyme,
      the structure of different class III gene promoters, the preinitiation complex
      assembly and the transcription cycle. The second part of the review is devoted to
      the regulation of class III gene transcription in dependence on cell cycle stage,
      growth factor influence and cell growth rate, during cell transformation and
      apoptosis.

PMID- 15856941
TI  - [Analysis of nucleotide sequences polymorphism of its regions of ribosomal genes
      of diploid Aegilops (L.) species].
AB  - rDNA sequences of ITS region including full sequences of ITS1, 5.8S and partly
      sequenced ITS2 of 22 accessions of 5 diploid Aegilops species, were determined.
      The full alignment length was 524 bp. The analysis of ITS sequences shows a
      number of species-specific nucleotide changes. For the first time for diploid
      Aegilops species an interspecific polymorphism was shown. In some positions the
      polymorphism within accessions was determined. It can be differences either
      between or within individual plants. In general both inter- and intraspecific
      polymorphism of ITS sequences was very low. Nucleotide polymorphism was
      determined only in 25 sites, 12 of which were informative.

PMID- 15856942
TI  - [Construction and characterization of normalized cDNA library of maize inbred
      Mo17 from multiple tissues and developmental stages].
AB  - Comprehensive complementary DNA (cDNA) library is a valuable resource for
      functional genomics. In this study, we set up a normalized cDNA library of Mo17
      (MONL) by saturation hybridization with genomic DNA, which contained expressed
      genes of eight tissues and organs from inbred Mo17 of maize (Zea mays L.). In
      this library, the insert sizes range from 0.4 kb to 4 kb and the average size is
      1.18 kb. 10.830 clones were spotted on nylon membrane to make a cDNA microarray.
      Randomly picked 300 clones from the cDNA library were sequenced. The cDNA
      microarry was hybridized with pooled tissue mRNA probes or housekeeping gene cDNA
      probes. The results showed the normalized cDNA library comprehensively includes
      tissue-specific genes in which 71% are unique ESTs (expressed sequence tags)
      based on the 300 sequences analyzed. Using BLAST program to compare the sequences
      against online nucleotide databases, 88% sequences were found in ZmDB or NCBI,
      and 12% sequences were not found in existing nucleotide databases. More than 73%
      sequences are of unknown function. The library could be extensively used in
      developing DNA markers, sequencing ESTs, mining new genes, identifying positional
      cloning and candidate gene, and developing microarrays in maize genomics
      research.

PMID- 15856943
TI  - [The development of yeast vector system for study of regulational functions of
      eukaryotic noncoding elements].
AB  - The original yeast vector system was proposed for study of regulation functions
      of eukaryotic noncoding sequences. This system consists of two reporter genes
      that arranges in opposition to one another. The promoter activity of LTR HERV-K
      of locus 22-19 in 7p22 human chromosome was studied. It was shown that the LTR
      initiates transcription of reporter gene in yeasts in forward and reverse
      orientation with respect to the reporter. It was displayed that the LTR 22-19
      HERV-K possesses bidirectional promoter activity in the yeast vector system.
      Comparison of the promoter activity LTR 22-19 and strong GAL1 and TDH promoters
      in yeasts Saccharomyces cerevisiae shown that promoter activity of the LTR amount
      approximately 0.34% for promoter activity of the inducible GAL1 promoter and
      0.26%--of the constitutive TDH promoter.

PMID- 15856944
TI  - [Identification and characterization of differentially expressed ESTs of
      Gossypium barbadense infected by Verticillium dahliae with suppression
      subtractive hybridization].
AB  - Cotton wilt defense reaction is a complicated continuous process and involves a
      battery of genes. In this study, we adopted suppression subtractive hybridization
      (SSH) technique to isolate differentially expressed ESTs from Gossypium
      barbadense variety 7124 during Verticillium wilt defense process. An array of
      1165 clones from the subtractive library has been screened with reverse northern
      blotting, of which 131 ESTs were considered as over-expressed and 16 ESTs were
      down-regulated. Sequence analysis and blast search showed that 83 ESTs were
      homologous to 45 unique sequences in the databases. Among all these
      differentially expressed ESTs, at least three kinds of genes were characterized.
      The majority of ESTs with deduced identity to aerobic metabolism enzymes strongly
      expressed in the infection process. Likewise, ESTs similar to those reported for
      pathogen-related protein genes were also picked out in this study. These ESTs in
      combination with other kinase-like genes and a defensin-like EST constituted an
      assembly of genes responded during pathogens' infection. These results imply that
      sea-island cotton undergoes strong oxidative stress and results in a series of
      defense responses when attacked by V. dahliae. To our knowledge, this is the
      first report on the isolation of global ESTs during sea-island cotton defense
      reaction.

PMID- 15856945
TI  - [Polymorphic markers of the NO synthase genes and genetic predisposition to
      diabetic polyneuropathy in patients with type 1 diabetes mellitus].
AB  - The allele and genotype frequencies of polymorphic markers of NOS1, NOS2 and NOS3
      genes, encoding three types of NO synthases, were compared in type 1 diabetes
      patients with and without diabetic polyneuropathty. 180 type 1 diabetes patients
      (T1DM) of Russian or Eastern Slavonic origin, living in Moscow city, were divided
      into two groups using non-overlapping (polar) phenotypes. 86 patients had overt
      DPN and T1DM duration in this group was less than 5 years (DPN+ group) and 94
      patients had no clinical DPN and T1DM duration was more than 10 years (DPN-
      group). We have not found the significant differences of allele and genotype
      frequencies of polymorphic markers (CA)n of NOS1 gene, (CCTTT)n of NOS2 gene,
      ecNOS4a/4b and Glu298Asp of NOS3 gene that indicates that all these markers are
      not associated with diabetic polyneuropathty. Only in the case of (CCTTT)n marker
      of NOS2 gene we have found a tendency for the association of 14 allele with DPN
      development. The carriers of this allele have the lower risk of DPN in T1DM.

PMID- 15856946
TI  - [Association of polymorphic markers of lipid metabolism genes with diabetic
      polyneuropathy in type 1 diabetes mellitus].
AB  - The aim of this study was the search of association with diabetic polyneuropathy
      of the polymorphic markers epsilon2/epsilon3/epsilon4 of apolipoprotein E (APOE)
      and I/D of apolipoprotein B (APOB) genes in groups of type 1 diabetes patients
      with diabetic polyneuropathy (n = 86) and without its clinical signs (n = 94). We
      have not found significant association with diabetic polyneuropathy (DPN) of
      epsilon2/epsilon3/epsilon4 marker of APOE gene. However the comparison of allele
      and genotype frequencies of I/D marker of APOB gene showed that the carriers of I
      allele and II genotype had higher risk (OR = 1.66 and 2.01, relatively; p <
      0.027), whereas the carriers of D allele had lower risk of DPN (OR = 0.60; p <
      0.018). Our findings show that APOB gene, encoding one of the main components of
      lipid metabolism system, is involved into the diabetic polyneuropathy development
      in type 1 diabetes mellitus.

PMID- 15856947
TI  - [Parameters of binding and transport of oligodeoxynucleotide, which includes BCL2
      mRNA translation start, to the K562 cells].
AB  - Interaction of oligodeoxynucleotides (ODN), 18-mer, which included sequence of
      BCL2 mRNA translation start, with K562 cells has been studied. The kinetic curves
      of interaction showed that oligonucleotide total binding with the cells at 37
      degrees C and low oligonucleotide concentration (< or = 30 nM), as well as under
      lipofection, were composed of two processes: 18-mer surface binding with cell
      membranes and its non-proportional internalization into the cells. The last, in
      turn, consisted of three consequent steps. The enhanced extent and rate of
      oligonucleotide internalization was diminished after first hour incubation and
      later they were increased again. This reflected rising additional binding sites
      that provided internalization. At chosen time-points the internalization of ODN
      into cells, been proceeded at 37 degrees C, were at most abruptly abrogated by
      cooling down. ODN to K562 cell membrane binding constants and specific number of
      binding sites have been determined. Time-intervals, providing equilibrium for
      each successive stage of multistep ODN bound/free determination, were maintained.
      It was established that receptor binding with increased binding constant (more
      than 2 x 10(9) M(-1)) promoted ODN internalization. Oligonucleotide binding and
      internalization with prolonged incubation were also up-regulated due to priming
      new binding sites of higher affinity. Lipofection enhanced ODN binding to cell
      membrane but conserved the main features of ligand-receptor interaction. During
      lipofection constants and ODN binding site numbers increased without changing the
      overall time-pattern of the process, observed for ODN without liposomes. Extent
      and rate of internalization of ODN in liposomal formulation did not differ
      substantially from ODN in solution.

PMID- 15856948
TI  - [Expression of genes for orthopoxviral TNF-binding proteins and study resulted
      recombinant proteins].
AB  - Genes for TNF-binding proteins (CrmBs) of variola virus (VARV), monkeypox virus
      (MPXV) or cowpox (CPXV) were isolated with PCR from viral genomes and expressed
      within baculovirus DNAs in Sf21 insect cell line. Properties of resulted
      recombinant proteins were studied with physical-chemical and immunological
      methods. It was shown with solid phase enzyme-linked immunoassay that viral
      proteins inhibited hTNF binding with polyclonal hTNF-antibodies. The strongest
      inhibitor was VARV-CrmB, the less one was MPXV-CrmB. Biological activity of
      recombinant protein preparations was studied in the test of neutralization of TNF
      cytotoxicity for L929 murine fibroblast cells. It was shown that recombinant
      CrmBs neutralized cytotoxicity of hTNF, mTNF or rTNF in species-specific manner.
      It was shown also that effectiveness of hTNF cytotoxicity inhibition in vitro
      with VARV-CrmB exceeded the same effect of polyclonal hTNF-antibody. A
      possibility of the elaboration of new therapeutics for anti-TNF therapy on the
      base of CrmB-like proteins is discussed.

PMID- 15856949
TI  - [Dependence of aminoglycoside 3'-phosphotransferase VIII activity on protein
      serine/threonine kinases in Streptomyces rimosus].
AB  - In Streptomyces rimosus, selection with aminoglycoside kanamycin triggers
      "silent" aminoglycoside 3'-phosphotransferase (aph) VIII gene. Expression of
      aphVIII was accompanied by amplification of a chromosomal DNA fragment, which
      contained aphVIII. Earlier, S. rimosus aphVIII gene was isolated, sequenced, and
      deduced APHVIII protein sequence was reported. Using in vitro labeling and
      immunoprecipitation with anti-APHVIII antibody, we demonstrate that one of the
      abundant proteins phosphorylated by endogenous protein kinases (PKs) in extracts
      of S. rimosus strain S683 is APHVIII. Phosphoamino acid assay has shown
      phosphorylation of two seryl residues in APH molecule. The amount of phosphate
      incorporated into APHVIII in the presence of Ca2+ was 1.84-fold as much as that
      detected without Ca2+. As shown by in the gel self-phosphorylation and in the
      substrate-containing gel phosphorylation analyses, two serine PKs with molecular
      masses of 74 kDa and 55 kDa were active against APHVIII. The 55-kDa PK showed a
      clear Ca2+ and calmodulin dependency in activity. The specific kanamycin
      phosphotransferase activity of exhaustedly phosphorylated APHVIII was 3.72-fold
      as much as that detected in the preparation of nonphosphorylated enzyme. These
      results suggest involvement of PKs under study in the modulation of APHVIII
      aminoglycoside phosphorylating activity and in the generation of kanamycin
      resistance in S. rimosus.

PMID- 15856950
TI  - [Early and late responses to oxidative stress in human dermal fibroblasts of
      healthy donors and rheumatoid arthritis patients. Relationship between the cell
      death rate and the genomic dosage of active ribosomal genes].
AB  - A study was made of the effect of the oxidizing agent potassium chromate (K2CrO4,
      PC) on cultured dermal fibroblasts of a healthy donor and three patients with
      rheumatoid arthritis (RA). Characteristics of the rRNA gene (RG) complex-RG copy
      number, active RG (ARG) dosage, and 18S rRNA content--were determined for each
      cell line. In cells of the healthy donor, oxidative stress caused by low doses of
      PC (2-4 microM, 1-4 h) induced an early response, including a 50-80% increase in
      total RNA and rRNA. An appreciable activation of the nucleolus was observed
      cytochemically, by silver staining and morphometry. The early response grew
      considerably lower with the increasing passage number and/or PC concentration.
      Exposure to 6-12 microM PC for 24 h led to a progressive cell death (late
      response). The existence and intensity of the early response correlated
      positively with the cell survival during further culturing. Cells of the RA
      patients displayed almost no early response even at early passages: total RNA did
      not increase, and rRNA increased by no more than 10%. Cell disruption (apoptosis)
      during further culturing was more intense than in the line originating from the
      healthy donor. The apoptosis intensity characterized by the increase in the
      content of DNA fragments in the culture medium and in the caspase 3 activity, was
      inversely proportional to the ARG dosage in the genome. The results provide the
      first quantitative characterization of the early and late responses of cells to
      PC-induced oxidative stress and suggest a role of the ARG dosage in cell survival
      in stress.

PMID- 15856951
TI  - [DNA macroarray analysis of gene expression changes in rat brain after single
      administration of 2-aminoadamantane compound].
AB  - We have used the Rat Atlas cDNA Array ("BD Bioscience") to assess changes in mRNA
      expression of 588 genes in rat brain after acute treatment of 2-aminoadamantane
      compound--Ladasten. Drug exhibits the psychostimulating and anxyolitic actions.
      The analysis of results of hybridization on macrochips and their corroboration by
      quantitative real-time RT-PCR has allowed to reveal 12 genes, expression of which
      changes in response to ladasten in rat brain cells. The GAT3 and CARBH genes
      should be considered as primary pharmacologically significant targets and the
      changes of their functional conditions allows to explain the distinct mechanisms
      of anxyolitic properties of the drug. It was shown that Ladasten induced genes
      are involved in the different signalling pathways (APC, Rb, PKCIP, PMCA), genes
      encoding the cytosceletal proteins (Tubal, actin), synaptic proteins (Syn IA&IB,
      PLP) and metabolism enzymes (Gapdh, NSE). It is possible to assume, that
      proteins, encoded by the given genes participate in the compensatory and/or
      neuroplastic adaptation to biochemical effects of Ladasten.

PMID- 15856953
TI  - [The unbalance of membrane phospholipid composition of Escherichia coli affects
      the PPHO promoter activity].
AB  - Activity of phosphate PPHO or arabinose PBAD promoter of Escherichia coli has
      been studied depending on the content of zwitter-ionic phosphatidylethanolamine
      (PE) and anionic phospholipids in membranes. In the absence of PE or under
      significant decrease in the content of anionic phospholipids, there is a
      significant decline of PPHO promoter activity but not PBAD promoter. Since the
      PPHO promoter belongs to the Pho-regulon--a member of the family of two-component
      regulatory systems of signal transduction having membrane sensors, the regulation
      of gene expression by phospholipids is presumed to be realized through a membrane
      sensor.

PMID- 15856952
TI  - [Retroviral reporter systems for the assessment of activity of stress-induced
      signal transduction pathways controlled by p53, HIF-1 and HSF-1 transcription
      factors].
AB  - Tumor suppressor p53, hypoxia-inducible factor 1 (HIF-1) and heat-shock factor 1
      (HSF-1) are involved as the key transcription factors in cellular response to
      stress, induced by genetic material damage, hypoxia and heat shock respectively.
      The protein factors listed above also play an integral part in tumor development
      and progression. Thus, modulation of their activity may be important for
      treatment of cancer. In our work we obtained the reporter constructs for
      quantitative assessment of p53, HIF-1 and HSF-1 transcriptional activity on the
      basis of retro- and lentiviruses, allowing to obtain reporter cell lines almost
      out of any cell type. Induction of beta-galactosidase reporter gene expression,
      reflecting the activity of p53 and HIF-1 factors, depends on dose of treatment
      and also correlates with the induction of the endogenous target genes expression.
      The observed effect of activating treatments completely disappeared when the
      expression of p53 and HIF-1 genes was inhibited with specific siRNAs. The
      obtained reporter constructs may find the application in the screening of
      chemical and genetic (such as siRNA- and cDNA-libraries) modulators of
      transcriptional activity along with the investigation of components of signal
      transduction pathways modulating the transcriptional activity of those factors.

PMID- 15856954
TI  - [Conservative motif CMLD in silicic acid transport proteins of diatom algae].
AB  - Sequencing of fragments of genes coding for silicic acid transport (SIT) proteins
      of diatoms of evolutionary distant classes (centric Chaetoceros muelleri
      Lemmermann, pennate araphid Synedra acus Kutzing, pennate raphid Phaeodactylum
      tricornutum Bohlin, and pennate with keeled raphe system Cylindrotheca fusiformis
      Reimann et Lewin), revealed the presence in these proteins of a conservative
      amino acid motif CMLD. Hydropathy profiles suggest that CMLD occupies a position
      between two transmembrane strands which do not contain lysine and arginine
      residues. The two strands are good candidates for the role of the channel along
      which transport of silicic acid occurs. CMLD is a rare motif. Diatoms are known
      to need Zn2+ for the incorporation of silica. Presumably, CMLD is the site of
      Zn2+ binding of SITs. We found that the growth of diatoms is inhibited by a
      negatively charged alkylating reagent 5-(2-iodoacetamidoethyl)aminonaphtalene-1
      sulfonic acid which cannot penetrate through the cell membrane. Cysteine of CMLD
      can be a target of this reagent. Synthetic peptide NCMLDY forms a complex with
      Zn2+, as revealed by the fact that the ion considerably reduces the rate of
      alkylation of the peptide.

PMID- 15856955
TI  - [ADP-ribosylation intensifies cleavage of DNA loops in the nuclear matrix].
AB  - Using DNA pulse field electrophoresis it has been shown that ADP-ribosylation in
      the nucleoids of human mononuclear leukocytes and rat brain cortex neurons
      stimulates cleavage of DNA loops at their attachmant sites to the nuclear matrix.
      The conclusion has been drawn suggesting possible participation of ADP
      ribosylation in DNA-topoisomerase II activity modulation in the nuclear matrix of
      eukaryotic cells.

PMID- 15856956
TI  - [Investigation of periodic distributions of amino acids in the sequences of fiber
      proteins of bacteriophage T4].
AB  - Sequences of amino acids of some fiber proteins may have a periodic structure. To
      analyze this periodicity Fourier transform of a mathematical image of symbolic
      sequence of amino acids in a protein is sometimes used. In this work we employed
      one (out of few possible) particular way of doing Fourier transform as the most
      straightforward and optimal. Employing this optimal Fourier transform method we
      analyzed periodicity of fiber proteins in bacteriophage T4. As a result we
      managed to confirm that a certain periodicity exists in the investigated
      proteins. It was found that for a number of proteins the alternation of elements
      of the same group in the amino acid sequence with a rather small period T = 15
      exists, whereas for some other proteins alternations have small periods 10 and 8.
      The new result is a discovery of relatively large periods of amino acids
      alternations, which divide the amino acids sequence of the protein into 4 or 6
      equal parts. These data on the amino acids periodicity allowed us to align amino
      acids sequences in accordance with the established periods of both types, in
      agreement with certain results obtained in X-ray crystallography and electron
      microscopy experiments.

PMID- 15856957
TI  - [Investigation of apomyoglobin stability depending on urea and temperature at two
      different pH values].
AB  - Equilibrium unfolding of apomyoglobin by urea was investigated in the temperature
      range from 5 to 25 degrees C at two pH values. The thermodynamic parameters of
      the apomyoglobin native-unfolded state transition were determined. Conformational
      changes in the protein structure were monitored by tryptophan fluorescence and
      far UV circular dichroism. Apomyoglobin preserves its native conformation at pH
      5.7 and 6.2 in the temperature range used. It was shown that the apomyoglobin
      stability and its unfolding cooperativity are substantially lower at 5 degrees C
      than at other temperatures. This fact should be taken in account at the
      investigation of apomyoglobin.

PMID- 15856958
TI  - [Structural analysis of the complex of phenoxazone antibiotic actinocyl-bis-(2
      deoxytetranucleotide 5'-d(TpGpCpA) by the methods of two dimensional 1H-NMR
      spectroscopy and molecular mechanics].
AB  - The spatial structures of intercalated complexes of synthetic phenoxazone
      antibiotic actinocyl-bis-(2-dimethylaminoethyl) amide with self-complementary
      deoxytetranucleotide 5'-d(TpGpCpA) have been investigated. Analysis has been made
      using two-dimensional NMR (2D-NOESY) data in aqueous solution and molecular
      mechanics simulation. Distinctive features of the conformation of drug-DNA
      complexes have been determined at two possible orientations of the chromophore of
      phenoxazone antibiotic at the intercalation site.

PMID- 15856959
TI  - [Construction of vector system for molecular cloning in Bacillus subtilis and
      Escherichia coli].

PMID- 15856960
TI  - Mirror, mirror on the wall, who is the fairest of us all?

PMID- 15856961
TI  - Skimming the surface: a brief history of skin conditions.

PMID- 15856962
TI  - Is cultural sensitivity sometimes insensitive?

PMID- 15856963
TI  - Trick or treating in Orlando.

PMID- 15856964
TI  - Pregnant "DES daughters" and their offspring.
AB  - QUESTION: I am a 34-year-old woman in my second trimester of pregnancy. My mother
      took diethylstilbestrol when she was pregnant with me. Could my expected child be
      affected by this? ANSWER: Animal studies suggest the child could be affected, but
      little data on humans strongly support this. You could plan to have your child
      monitored for a potential, though unlikely, effect.

PMID- 15856965
TI  - A major pain in the neck. Spinal epidural hematoma.

PMID- 15856966
TI  - Dermacase. Dermatophyte infection (tinea).

PMID- 15856967
TI  - Dermacase. Essential or primary hyperhidrosis.

PMID- 15856968
TI  - Dermacase. Trichotillomania.

PMID- 15856969
TI  - Dermacase. Henoch-Schonlein purpura.

PMID- 15856970
TI  - Benzodiazepine use in British Columbia: is it consistent with recommendations?

PMID- 15856971
TI  - Topical therapies for psoriasis: evidence-based review.
AB  - OBJECTIVE: To review current understandings of and approaches to topical
      psoriasis therapies and to assess their efficacies and adverse effects. QUALITY
      OF EVIDENCE: Literature from 1987 to 2003, inclusive, was reviewed via MEDLINE
      using the search term "psoriasis" combined with "topical treatment." Articles
      were prioritized based on their level of evidence, favouring double-blind,
      randomized controlled trials over other comparison studies. Other studies were
      included where level I research was unavailable. No level III research was
      included. MAIN MESSAGE: Psoriasis is very common and causes substantial
      morbidity. Because most psoriasis is mild to moderate, patients are well suited
      to outpatient topical therapy. Advances in topical treatments for psoriasis have
      kept pace with a rapidly evolving comprehension of its pathogenesis, making a
      review of current therapies useful for those who treat psoriasis. While research
      supports continued reliance on corticosteroids as first-line therapy, comparable
      efficacy has been shown for vitamin D analogues and topical retinoids, albeit
      with a slight increase in adverse effects. CONCLUSION: The combination of
      steroids and vitamin D analogues or topical retinoids is perhaps the most
      promising current treatment. It seems to have increased efficacy and fewer side
      effects.

PMID- 15856973
TI  - Importance of Mainpro-C.

PMID- 15856972
TI  - Acneiform facial eruptions: a problem for young women.
AB  - OBJECTIVE: To summarize clinical recognition and current management strategies
      for four types of acneiform facial eruptions common in young women: acne
      vulgaris, rosacea, folliculitis, and perioral dermatitis. QUALITY OF EVIDENCE:
      Many randomized controlled trials (level I evidence) have studied treatments for
      acne vulgaris over the years. Treatment recommendations for rosacea,
      folliculitis, and perioral dermatitis are based predominantly on comparison and
      open-label studies (level II evidence) as well as expert opinion and consensus
      statements (level III evidence). MAIN MESSAGE: Young women with acneiform facial
      eruptions often present in primary care. Differentiating between morphologically
      similar conditions is often difficult. Accurate diagnosis is important because
      treatment approaches are different for each disease. CONCLUSION: Careful visual
      assessment with an appreciation for subtle morphologic differences and associated
      clinical factors will help with diagnosis of these common acneiform facial
      eruptions and lead to appropriate management.

PMID- 15856974
TI  - "Is there a doctor on the plane"?

PMID- 15856975
TI  - [The spatial organization and conformational flexibility of neuropeptides of the
      gallatostatin family].
AB  - The spatial organization and conformational flexibility of neuropeptides of the
      gallatostatin family was studied by the method of theoretical conformational
      analysis. It was found that the spatial organization of neuropeptides allows the
      realization of folded helical structures of the C-terminal pentapeptide, and the
      flexibility of neuropeptides is due to a great number of low-energy states in the
      N-terminal fragment of the molecule.

PMID- 15856976
TI  - [Structure-function organization of neurokinin A and neurokinin B molecules. I.
      Theoretical conformational analysis of neurokinin A].
AB  - The spatial structure of the neurokinin A molecule was studied by the method of
      theoretical conformational analysis. On the basis of fragmental analysis, stable
      structures of the neurokinin A molecule under polar conditions were determined.
      The structures can be described by four families of low-energy conformations
      having a relatively labile tripeptide at the C-end and a conformationally rigid
      heptapeptide at the N-end. It was shown that two of these conformations are
      virtually isoenergetic structures. One of these is an alpha-helical structure and
      the other forms two beta-turns at the N-terminus, which change to the turn of the
      alpha-helix at the C-end.

PMID- 15856977
TI  - [Critical phenomena, phase equilibria, and the temperature and structural optimum
      of homeostasis, as revealed by a model system water-biopolymer-electrolyte].
AB  - Equations of spinodal and two quasispinodals corresponding to critical and
      supercritical phase transitions leading to a rise of different dynamic structures
      of solution in the phase diagram of a model system water-biopolymer-electrolyte
      were obtained. The section of the phase diagram was considered where there exists
      the probability of quasi-equilibrium monomer-cluster and the principle of water
      ion homeostasis is realized. Based on these results, a possible mechanism of
      origination of unspecific adaptation reactions of a biomolecular system at the
      stage of chemical evolution was suggested.

PMID- 15856978
TI  - [NMR-relaxation in hydrated collagen from the spotted dogfish]].
AB  - Collagen samples from dog-fish egg case at different water content were studied
      by the 1H NMR relaxation method. The dependences of the proton spin-lattice and
      spin-spin relaxation rates on the concentration of water in hydrated native
      collagen were measured. The fractions of water protons of different mobility and
      their corresponding spin-spin and spin-lattice relaxation rates were determined
      in a multi-phase model of water protons in natural biopolymer-water systems. The
      correlation times were calculated as the characteristics of molecular motion in
      hydrated collagens with different content of absorbed water. The results obtained
      were compared with literature data of pulse NMR studies of molecular mobility in
      other collagen fibers.

PMID- 15856979
TI  - [Collagen structure and the disordering of the water subsystem in fibrillar
      polypeptides according to 2H-NMR data].
AB  - 2H NMR spectra of native collagen of rat tail tendon doped by 2H2O were studied.
      It was shown that the fine structure of 2H NMR multicomponent spectra is related
      to the diffusion mobility of constituent water molecules and their partial
      ordering. A bimodality of the distribution of the H2O ordering parameter was
      revealed, which corresponds to the alternation of dense and loose regions in the
      supramolecular structure of collagen-type polypeptides. The lower values of the
      ordering parameter correspond to loose regions of the structure characterized by
      the cooperative dynamics of polypeptide chains and water molecules.

PMID- 15856980
TI  - [Thermo- and photoinduced aggregation of alpha-crystallin].
AB  - Some properties of bovine alpha-crystallin, in particular its thermo- and
      photoaggregation, were studied by fluorescent spectroscopy of tryptophan residues
      and the probe 8-anilino-1-naphthalenesulfonate and light scattering. The
      effective diameter of a globule of native alpha-crystallin was 90 A, as estimated
      from the data on the polarization and lifetime of 8-anilino-1
      naphthalenesulfonate using the Levshin-Perren equation, and increases at an
      aggregation of no less than 140 A. The increase in the intensity of tryptophan
      fluorescence of alpha-crystallin during its thermo- and photodenaturation with
      the formation of aggregates is due to local conformational changes in the
      surroundings of tryptophan residues and light scattering. Tryptophan residues are
      buried in the interior of the aggregates. The thermoaggregation of the protein
      occurs not only at high temperatures. By approximating the experimental time
      dependence of slow spontaneous aggregation to the range of large times, the time
      of denaturation aggregation t(e) was found. For alpha-crystallin (at a
      concentration of 0.8 mg/ml in phosphate buffer at pH 8.4), t(e) at 70 degrees C
      is 100 h. This approach can be used in finding t(e) for any protein during its
      thermal treatment or long-term storage.

PMID- 15856981
TI  - [The formation of 8-oxoguanine and its oxidative products in DNA in vitro at 37
      degrees C].
AB  - The content of 8-oxoguanine, a biomarker of DNA damage by the action of reactive
      oxygen species, in native and denatured DNA upon heating at 37 degrees C was
      studied by the enzyme-linked immunosorbent assay using monoclonal antibodies
      against 8-oxoguanine. It was found that the content of 8-oxoguanine changes with
      time in a complicated multiphase manner, the maximum changes being as great as
      twofold. The production of hydrogen peroxide in water and 1 mM PBS, pH 6.8, at 37
      degrees C over a period of 50 h was determined by the method of enhanced
      chemiluminescence in a peroxide-luminol-p-iodophenol system. The generation of
      hydrogen peroxide also changed in a complicated multiphase manner. After heating
      the DNA at 80 degrees C for 24 h, guanine oxidation products were excised by 8
      oxoguanine-DNA-glycosylase. The products were separated and analyzed by liquid
      column chromatography on Sephadex LH-20 and Toyopearl HW-40 gel. The products
      were identified from UV adsorption spectra. The results indicated the generation
      of reactive oxygen species at 37 degrees C, which leads both to the generation of
      8-oxoguanine in DNA and its elimination as a result of its further oxidation. The
      oxidation of 8-oxoguanine was accompanied by the formation of a number of
      unstable products of further oxidation of 8-oxoguanine. Among these products,
      aminoimidazolone, spiroiminodigidantoin, and diiminoimidazole were identified
      from UV spectra. The appearance of the products of further oxidation of 8
      oxoguanine explains the origin of G : C --> C : G transversions by the action of
      reactive oxygen species.

PMID- 15856982
TI  - [The use of the spectrophotometric analysis for the calculation of the
      thermodynamic parameters in actinocin derivative-DNA systems].
AB  - The spectral properties of the actinocin derivative ActII in complexes with DNA
      were studied by UV visible spectrophotometry. Two binding models with one and two
      binding sites for competitive binding with different values of parameters were
      considered. To choose an optimal model of complexation, the optimization program
      of spectrophotometric concentration dependencies DALSMOD was used. Using this
      program, it was concluded that at least three complexes with different absorption
      spectra are present in the system ActII-DNA. The logarithms of K2 and K3 for DNA
      ActII mixtures, calculated for models I and II at different sodium ion
      concentrations, were in good agreement with predictions of the counterion
      condensation theory. The analysis of the absorption spectra of ActII-DNA mixtures
      at different temperatures made it possible to obtain the values of deltaH and
      deltaS for each type of complexes. The values of entropy deltaS were positive in
      the 0.02 M NaCl solution and negative in the 0.15 M NaCI solution.

PMID- 15856983
TI  - [A study of specific electrical conductivity of water by the action of constant
      magnetic field, electromagnetic field, and low-frequency mechanical vibrations].
AB  - The effect of a constant magnetic field, an electromagnetic field, and low
      frequency mechanical vibrations on specific electrical conductivity of distilled
      water was studied. Newly formed (fresh), three-day- and six-day-old distilled
      water was used. The exposure of distilled water to a constant magnetic field (2.5
      mT), electromagnetic field (2.5 mT and 1-100 Hz), low-intensity mechanical
      vibrations (1-100 Hz) with an intensity of 30 Db led to a reduction of its
      specific electrical conductivity. It was found that, as water aged, the effect of
      these factors on the specific electrical conductivity decreased.

PMID- 15856984
TI  - [A comparative study of the fluorescence properties of the chlorosomal antenna of
      the green bacterium from the family Oscillochloridaceae and the members from two
      other families of green bacteria].
AB  - The fluorescence properties of bacteriochlorophylls (BChl) of the chlorosomal
      light-harvesting antenna of Oscillochloris trichoides (strain DG-6) from a new
      family of green filamentous bacteria Oscillochloridaceae were investigated in
      comparison with green bacteria from two other families. A strong dependence of
      the fluorescence intensity of chlorosomal bacteriochlorophyll c of Osc.
      trichoides on the redox potential of medium was found, which previously was
      observed only in green sulfur bacteria. The presence of BChl a in chlorosomes did
      not appear in their absorption spectra but was visualized by fluorescence
      spectroscopy at 77 K. From the comparative analysis of fluorescence spectral data
      for the chlorosomal light-harvesting antenna of Osc. trichoides and similar
      spectral data for green bacteria from two other families, it was concluded that,
      in some fluorescence spectral features (spectral position of bacteriochlorophyll
      c/a fluorescence bands; shape and full width at half maximum fluorescence band of
      chlorosomal bacteriochlorophyll c; the Stokes shift value of bacteriochlorophyll
      c band; a high molar ratio of bacteriochlorophyll c : bacteriochlorophyll a in
      chlorosomes that makes the bacteriochlorophyll a fluorescence band unresolved at
      room temperature; and highly redox-dependent fluorescence intensity of
      chlorosomal bacteriochlorophyll c), Osc. trichoides chlorosomes are close to the
      chlorosomal antenna of Chlorobiaceae species.

PMID- 15856985
TI  - [Low-density lipoproteins with different capacity for aggregation].
AB  - Preparations of low-density lipoproteins from healthy donor blood contain
      lipoprotein particles with different capacity for aggregation: upon stirring,
      some particles form aggregates significantly more quick than others. After
      stirring, lipoprotein particles are separated by ultracentrifugation into two
      fractions: a fraction of large aggregates and a fraction of small particles
      without intermediate forms. It is known that lipoprotein aggregates can
      accelerate intracellular accumulation of lipids. Therefore, it is supposed that
      particles of high aggregation ability are more atherogenic.

PMID- 15856986
TI  - [Dependence of the concentration of the demi-maximal action of a channel blocker
      on the agonist concentration].
AB  - Based on the analysis of kinetic scheme of blocking of open channels at any
      number of blocker binding sites, the dependence of current on blocker
      concentration was found. A variant of this dependence for a trapping blocker was
      also found. The restrictions of the applicability of the Hill equation and the
      necessity of taking into account the dependence of the concentration of demi
      maximal blocker action (IC50) on the concentration of agonist were shown.

PMID- 15856987
TI  - [Effect of nitric oxide on viscosity of nerve cell membranes].
AB  - The influence of nitric oxide on the microviscosity of nerve cell membranes was
      investigated by resonance Raman (RR) spectroscopy. Changes in membrane viscosity
      were estimated from the resonance Raman-spectra of carotenoids localized in the
      axon plasmatic membrane and membranes of subcellular vesicles (cytosomes). For
      the nerve fibre, the extracellular addition of nitric oxide donor, sodium
      nitroprusside (0.5 mM), caused an increase in the 1526 cm(-1) band relative half
      width and the modification of 1160 cm-1 band structure. Moreover, sodium
      nitroprusside led to an increase in the I1526/I1160 ratio by 13% in 25 min and a
      decrease in this ratio by 10% in 50 min. In the case of cytosomes, sodium
      nitroprusside (0.5 mM) resulted in the reduction of the I1526/I1160 ratio by 8%
      in 25 and 50 min. It was shown that the neuron rhythmic activity correlated with
      the I1526/I1160 ratio and cytosome membrane microviscosity. We suppose that
      nitric oxide causes a conformational transition of carotenoids in the axon
      plasmatic membrane and the membranes of cytosomes. This process can be due to
      nitric oxide-induced changes of the membrane microviscosity or potential.

PMID- 15856988
TI  - [Myoglobin and mitochondria: kinetics of oxymyoglobin deoxygenation in
      mitochondria suspension].
AB  - The kinetics of whale MbO2 deoxygenation was studied spectrophotometrically in
      the presence of breathing rat mitochondria under conditions when mitochondria
      were separated from the protein solution by a semipermeable film capable to
      transfer only low-molecular-weight compounds and directly in the solution of MbO2
      with mitochondria (incubation medium: 15-35 mM succinate, 150 mM sucrose, 100 mM
      KCl, 0.5 mM EGTA, 5 mM KH2PO4, 10 mM MOPS, pH 7.4). It was shown that the
      splitting of O2 from MbO2 at physiological pO2 is possible only if it directly
      contacts mitohondria. The deoxygenation rate does not depend on the protein
      concentration (zero order on [MbO2] as opposite to the first order reaction in
      the absence of mitochondria) and completely coincides with the rate of oxygen
      consumption by mitochondria under the same conditions, as indicated by the
      polarographic data. The dependence of the MbO2 deoxygenation rate on the
      concentration of mitochondria and the protein, and on the total charge of the
      MbO2 molecule was studied using horse MbO2 (pI 7.1), sperm whale MbO2 (pI 8.3),
      its zinc complex, Zn-MbO2 (pI > 8.3), and the sperm whale MbO2 derivative
      carboxymethylated at His residues, CM-MbO2 (pI 5.2). The mechanism of MbO2
      deoxygenation in the cell obviously actuates its interplay with the mitochondrial
      membrane. As a result, the affinity of Mb to oxygen decreases several times,
      which corresponds to a shift of the Mb dissociation curve to higher pO2 values.

PMID- 15856989
TI  - [The indirect effect of hemoglobin on the electrophoretic mobility of human blood
      erythrocytes].
AB  - Using the factor analysis, it was shown that the total content of hemoglobin in
      human blood plays a limited and indirect role in the regulation of average
      electrophoretic mobility of erythrocytes. In this case, it is not the only
      parameter governing this level. The statistical relationship between the total
      content of hemoglobin and erythrocyte mobility in electrical field is not stable
      and is determined by the dependence of both indices on their common factor of
      control of erythroid homeostasis.

PMID- 15856990
TI  - [Interaction of nonelectrolytes, the derivatives of 5-hydroxybenzimidazole, with
      erythrocyte membrane].
AB  - The method of spin probe and scanning electron microscopy were used to study the
      effects of some new synthetic antioxidants and bioregulators, the derivatives of
      5-hydroxybenzimidazole, on the membrane structure and morphology of erythrocytes.
      Analysis of EPR spectra and electron micrographs revealed that the derivatives
      with various side substituents affect the membrane structure and shape of
      erythrocytes in a concentration-dependent manner, the effect correlating with the
      hydrophobic properties of the side derivatives. It was shown that all the
      compounds in the concentration range 1.10(-7) - 1.10(-3) M exhibit the
      echinocytogenic action, the most profound effect being found in the compound with
      benzyl- and ethoxygroup in sites 2 and 5, respectively. Our data suggest that
      nonelectrolytes, the derivatives of 5-hydroxybenzimidazole, are located in the
      outer monolayer of erythrocyte membrane.

PMID- 15856991
TI  - [Investigation of electrophysical properties of Listeria monocytogenes cells
      during the interaction with monoclonal antibodies].
AB  - An electrooptical approach was used in studies of Listeria monocytogenes-antibody
      binding. An electrooptical analyzer, which has been developed at the State
      Research Center for Applied Microbiology (Obolensk, Russia), was used as a basic
      instrument for electrooptical measurements. The analyzer consists of the
      following modules: a sample preparation module, a mixer, an AC field generator,
      an EO-flow cell, a microcontroller for transfer of liquid, a thermal system, an
      operator interface, and an image processor. The sample preparation module
      includes a unit for an automatic filter changing device and a hydraulic system.
      Since the AC electrokinetic effects depend on the dielectric properties of
      bioparticles, their composition, morphology, phenotype, the medium, and the
      frequency of applied electrical field, the electroorientational spectra were used
      for discrimination of different types of bacteria, a given type being
      "controlled" (and identified) by the selective choice of binding agents
      (antibodies). The measurements were performed using a discrete set of frequencies
      of the orienting electric field (10, 100, 250, and 500 kHz). During biospecific
      interactions, an antibody is bound to the microorganism, causing a change in the
      dielectric properties of the microorganism-antibody complex, and the electrooptic
      signal reaches its maximum at 100-200 kHz. It was shown that the biospecific
      interactions of Listeria monocytogenes cells with anti-Listeria antibody in the
      presence of E. coli K-12, and A. brasilense sp7 significantly change the
      electrooptical signals. Thus, the determination of the presence of particular
      bacteria within a mixed sample may be achieved by selection and matching of
      antibodies specific to individual bacterium types and by comparing the spectra of
      bacterium in the presence and in the absence of specific binding agent
      (antibody).

PMID- 15856992
TI  - [Motionless dissipative structures formed by soil bacteria].
AB  - A model of the stationary distribution of bacteria in soil, formed upon
      filtration of soil solution was constructed. The region of parameter values was
      determined at which the distribution is dissipative and has the form of
      alternating strips. Regularities in the degeneration of the dissipative structure
      as the parameters approach the boundary of the region were discovered. The
      analysis was made using qualitative, analytical and quantitative investigation of
      differential equations of the transfer. Data on the growth, nourishment, and
      death of copiotrophic bacteria were used in the calculations.

PMID- 15856993
TI  - [Consideration of a priori information and type of an experimental error using
      the method of system identification based on the minimal quadratic discrepancy
      criterion].
AB  - The variants of the identification method were considered that take the a priori
      information about the evolution of a system under study and the type of
      experimental errors of the dynamic parameters of the system into account. An
      example of using this method for the identification of a biochemical reaction is
      given where the error in measuring the dynamic parameters (concentration of
      substances) has both an absolute and a relative components.

PMID- 15856994
TI  - [The ontogenetic approach to chlorophyll fluorescence studies of plant
      photosynthetic apparatus under stressful conditions].
AB  - Based on the analysis of reasons limiting the application of the method of
      chlorophyll fluorescence induction for estimating the state of the leaf
      photosynthetic apparatus under prolonged stress, the necessity of the ontogenetic
      approach consisting in a more exact determination of leaf age was substantiated.
      A comparison of the calendar and ontogenetic ways of determination of age of
      cucumber leaves under controlled conditions revealed essential distinctions in
      the estimation of plant leaf photosynthetic apparatus by the method of
      chlorophyll fluorescence induction for two variants distinguishing by the
      cultivation light regime ("white", 400-700 nm, and "red", 600-700 nm). It was
      shown that, in the case of prolonged effect of the stress factor on the plant,
      the unambiguity of the interpretation of chlorophyll fluorescence induction
      parameters in the estimation of the state of their photosynthetic apparatus
      depends essentially on the choice of the ontogenetic period of leaves of plants
      being compared and the accuracy of determination of leaf age.

PMID- 15856996
TI  - [The resolution capacity and the accuracy of acoustic measurement of sound
      frequency].
AB  - It was shown that processes occurring in the internal air cochlea, which
      represents a wave guide with a travelling wave and resonance in the critical
      layer, are crucial for the resolution capacity and the accuracy of measurement of
      sound frequency by an acoustic analyzer.

PMID- 15856995
TI  - [The physical properties of the synovial fluid as a lubrication of joints].
AB  - The properties of the synovial fluid and the results of the electrophysical
      studies of the fluid by the thermoelectret method are briefly described. The
      interrelation between current peaks on the thermostimulated current spectra of
      thermostimulated currents of the synovial fluid and the liguid-crystalline state
      of its components was established. The results can be used for developing the
      methods of diagnostics of synovial joint diseases and design of artificial
      joints.

PMID- 15856997
TI  - [A comparison of some biomechanical characteristics of the middle ear of living
      man and a cadaver].
AB  - The biomechanical characteristics of the middle ear of a live man and a corpse
      (autopsy material) were compared. The conditions were found that provide the
      adequacy of biomechanical reactions of both objects to changes in the external
      air pressure.

PMID- 15856998
TI  - [Dependence of magnetic suspectibility of various biological objects on their
      physiological conditions and viability].
AB  - The magnetic susceptibility of seeds of cereals and worker honey bees was
      studied. A correlation between the magnetic susceptibility of bioobjects and
      their physiological state was established. The theory of magnetic orientation of
      migrating animals is discussed.

PMID- 15856999
TI  - [The influence of a low- and high-frequency electromagnetic fields on seeds].
AB  - It was shown that the exposure of seeds in the rest phase to a low-frequency
      pulse electromagnetic field leads to substantial changes in seed physiology
      during germination. The changes at the physiological level in sprouting seeds
      depend not only on the frequency of the external EMF and its power
      characteristics but also on the kind of seeds. Low- and high-frequency
      electromagnetic fields are able to produce a biostimulation effect; however, the
      mechanisms of its appearance are different in their nature. The biochemical
      studies of seeds after EMF treatment in the modes resulting in expressed
      biological effects showed an increase in the activity of alpha-amylase, which
      testifies an increase in the gibberellin output and in the activity of the
      hydrolytic enzyme sour phosphatase. The response of seeds to EMF treatment
      demonstrates the possibility of electromagnetic control of growth processes.

PMID- 15857000
TI  - [Primary mechanisms of the biological effect of electromagnetic fields].
AB  - Based on the model of a bulk knitted structure, a possible mechanism of action of
      an external electromagnetic field on biological systems was proposed. The
      electromagnetic field affects biological processes through changes in the rates
      of biochemical reactions in response to changes in the conformational properties
      of water in the electromagnetic field.

PMID- 15857001
TI  - [Study of complexes of ethidium bromide with DNA by differential pulse
      voltammetry].
AB  - The interaction of ethidium bromide with calf thymus DNA was investigated by the
      method of differential pulse voltammetry. It was found that ethidium bromide
      binds with DNA in several ways. Corresponding values of the constants and the
      number of binding sites were determined. The intercalation, semi-intercalation,
      and electrostatic mechanisms of interaction were shown. The results obtained are
      in good agreement with the data obtained by spectroscopic (absorption and
      fluorimetric) methods.

PMID- 15857002
TI  - [The reverse turn of actin].
AB  - A model of actin sliding is proposed, which is based on the occurrence of actin
      myosin interactions and the generation in actin filaments of elastic deformations
      of torsion, compression, and tension. Previously in experiments in vitro, an
      unusually stable right-handed axial rotation of actin filaments sliding relative
      to myosin with a rotation pitch of 1 microm was observed. However, the reported
      value of the rotation pitch is significantly greater (14 times) than the pitch of
      actin right-handed double helix (72 nm), which supposedly determines the rotation
      pitch of actin. This result is explained in terms of the model by the presence of
      the reverse turn of actin at each elementary step.

PMID- 15857003
TI  - [The evaluation of the sizes of erythrocytes of the hibernating ground squirrel
      Citellus undulatus Pallas].
AB  - A topographical image of individual erythrocytes of the ground squirrel Citellus
      undulatus Pallas, in unfixed unstained smears was first obtained by scanning
      probe microscopy for two states of the animal: hibernation and the active state.
      The scannig of single discocytes, i.e. erythrocytes having a typical discal form,
      was fulfilled. For the active male, the diameter of the discocyte was found to be
      approximately 6500 nm. For the hibernating female, the diameter is approximately
      6000 nm. According to the data of light microscopy, the discocyte diameters are:
      6610 +/- 100 nm for the active state of animal and 6430 +/- 160 nm for the
      hibernating state.

PMID- 15857004
TI  - If you see primary hyperparathyroidism in mothers with vitamin-D deficiency
      osteomalacia: think of tertiary.

PMID- 15857005
TI  - Dissociation of clinical and laboratory diagnosis in hypothyroidism.
AB  - AIMS OF THE STUDY: To assess the significance of clinical versus biochemical
      diagnosis of hypothyroidism using a clinical scoring index and optimize the
      therapeutic dose of levothyroxine in Indian patients. METHODOLOGY: Three hundred
      and eighty eight cases of primary hypothyroidism (male:female ratio 1:5.8) were
      clinically classified as hypothyroid, euthyroid or inconclusive by Billewicz
      score. TSH estimation was repeated at 6-8 week intervals and appropriate
      adjustments in levothyroxine dosage made till the TSH was within the normal
      range. RESULTS: Of 388 biochemically confirmed hypothyroid subjects less than one
      fourth (21.6%) could be classified as hypothyroid, almost one half were euthyroid
      (48.4%) and the remaining (29.9%) fell in the inconclusive category according to
      Billewiz score. Of 227 patients who returned for complete follow up there was a
      positive correlation of replacement dose with age and initial weight in females,
      but not in males. Baseline TSH values were not found to have a significant
      correlation with the initial dose. The mean replacement dose of levothyroxine
      (T4) in our subjects was 109.4 +/- 24.05 microg/d (range 1.25-3.84 microg/kg).
      CONCLUSION: Clinical parameters alone fare poorly in establishing an unequivocal
      diagnosis of hypothyroidism. A biochemical confirmation is mandatory. The
      replacement done of T4 was found to be independent of the basal TSH level.

PMID- 15857006
TI  - Multiorgan dysfunction syndrome in sickle cell disease.
AB  - OBJECTIVE: Concurrent failure of multiple organs in patients of sickle cell
      disease (SCD) has rarely been reported. The main objective of this study was to
      highlight the multiorgan dysfunction (MODS) that occurs in some patients during
      sickle cell crisis. METHODS: Ten episodes of multiorgan failure were identified
      with sickle cell disease and defining criteria of organ failure of two or more
      organs that is lung, liver, or renal were established according to Acute
      Physiological and Chronic Health Evaluation - II (APACHE-II) criteria. RESULTS:
      Most episodes occurred during vaso-occlusive crisis, which was associated with a
      severe pain event. The onset of organ failure was associated with fever, rapid
      fall in haematocrit, platelet count and altered sensorium, later organ failure
      set in. Respiratory, hepatic, and kidney failure (all the three organs) were
      present in three of the ten patients who were in sickle crisis. Of this we lost
      one patient despite exchange transfusion and ventilator support. Of the four
      patients who had respiratory failure accompanied by hepatic failure, one patient
      died due to associated septicemia. Respiratory failure with renal involvement was
      seen in two patients whereas hepatic and renal failure was present in only one
      patient. Except for two, all other patients improved after aggressive blood
      transfusions. CONCLUSION: Acute multiorgan failure is a life threatening
      complication of SCD, which can exhibit without any evidence of chronic organ
      damage and is easily reversed by prompt and aggressive transfusion therapy.

PMID- 15857007
TI  - Kluver Bucy syndrome.

PMID- 15857008
TI  - Multiple myeloma presenting as a suprasellar plasmacytoma.

PMID- 15857009
TI  - High sensitive C-reactive protein: a novel biochemical markers and its role in
      coronary artery disease.
AB  - A series of prospective studies provide consistent data documenting that mild
      elevation of baseline levels of hs-CRP among apparently healthy individuals is
      associated with higher long-term risk for future cardiovascular events. This
      predictive capacity of hs-CRP is independent of traditional cardiovascular risk
      factors and offers a prognostic advantage over measurement of lipid alone. PHS
      and CARE trial suggest that the increased risk associated with systemic
      inflammation may be modified with certain preventive therapies and that
      inflammatory marker specifically hs-CRP may help to identify those who would
      benefit most from these pharmacological intervention. hs-CRP is the novel and
      evolving biomarker which provides a most useful predictive indicator for
      subsequent cardiovascular events. Based on various studies, increased hs-CRP
      levels in patients with high risk cardiovascular disease without documented CAD
      warrant treatment with statin even if LDL-C levels are within target range.
      Patients with documented CAD and high hs-CRP levels should be followed, and there
      risk factors should be managed aggressively.

PMID- 15857010
TI  - Medical philately (medical personalities on stamps)--Dr. Dwarkanath Kotnis.

PMID- 15857011
TI  - Epidemiology of diabetes in India--three decades of research.
AB  - India has nearly 33 million diabetic subjects today, which is briefly contributed
      by the urban population. The scenario is changing rapidly due to socio-economic
      transition occurring in the rural areas also. Availability of improved modes of
      transport, and less strenuously as in the vicinity have resulted in decreased
      physical activities. Better economic conditions have produced changes in diet
      habits. The conditions are more favourable for expression of diabetes in the
      population, which already has a racial and genetic susceptibility of the disease.
      Recent epidemiological data show that the situations are similar throughout the
      country. Prediabetic conditions like impaired glucose tolerance and impaired
      fasting glucose are also on the rise, indicating the possibility of further rise
      in the prevalence of diabetes. Metabolic syndrome, which is a constellation of
      cardiovascular risk factors, of which hyperglycaemia and insulin resistance are
      components, is also widely prevalent. The conversion to diabetes is enhanced by
      the low thresholds for the risk factors, such as age, body mass index and upper
      body adiposity. Indians have a genetic phenotype characterized by low body mass
      index, but with high upper body adiposity, high body fat percentage and high
      level of insulin resistance. With a high genetic predisposition and the high
      susceptibility to the environmental insults, the Indian population faces a high
      risk for diabetes and its associated complications. Early diagnosis of high risk
      groups and appropriate intervention by lifestyle modification may solution for
      the disease burden.

PMID- 15857012
TI  - Successful live related renal transplant in a case of tuberous sclerosis.
AB  - Tuberous sclerosis (TS) is an autosomal dominant multisystemic disease involving
      primarily the skin, the brain and the kidneys. Inspite of the kidney being
      involved in 40-80% of patients with this disease, the incidence of end stage
      renal disease is only about 1%. There are only 34 reported cases of successful
      renal transplantation in tuberous sclerosis patients with end stage renal
      disease. We report a case of successful renal transplantation in a patient of
      tuberous sclerosis with bilateral polycystic kidneys presenting with renal
      failure who also underwent bilateral native nephrectomies on follow up.

PMID- 15857013
TI  - Bilateral angle closure glaucoma following snake bite.
AB  - Snake venoms are complex heterogenous poisons with multiple effects. Ocular
      complications with snake bite are rare. This report describes two cases which
      developed bilateral acute angle closure glaucoma following snake bite. There was
      complete recovery in the two patients following timely diagnosis and treatment.

PMID- 15857014
TI  - Moya Moya disease : an unusual clinical presentation.
AB  - Moya Moya disease is a rare cause of stroke in adults, and is a rarity secondary
      to hepatitis C virus infection (HCV) and cryoglobulinemia (CG). We report such a
      rare association in a young patient who presented with intracerebral hemorrhage.

PMID- 15857015
TI  - Use of "Medicath" for safe pericardiocentesis.

PMID- 15857016
TI  - The impact of anti HPV vaccination on cervical cancer incidence and HPV induced
      cervical lesions: consequences for clinical management.
AB  - Cervical cancer is the second most common cause of cancer-related deaths in women
      worldwide. Screening for cervical cancer is accomplished utilizing a Pap smear
      and pelvic exam. While this technology is widely available and has reduced
      cervical cancer incidence in industrialized nations, it is not readily available
      in third world countries in which cervical cancer incidence and mortality is
      high. Development of cervical cancer is associated with infection with high risk
      types of human papillomavirus (HPV) creating a unique opportunity to prevent or
      treat cervical cancer through anti-viral vaccination strategies. Several
      strategies have been examined in clinical trials for both the prevention of HPV
      infection and the treatment of pre-existing HPV-related disease. Clinical trials
      utilizing prophylactic vaccines containing virus-like particles (VLPs) indicate
      good vaccine efficacy and it is predicted that a prophylactic vaccine may be
      available within the next five years. But, preclinical research in this area
      continues in order to deal with issues such as cost of vaccination in underserved
      third world populations. A majority of clinical trials using therapeutic agents
      which aim to prevent the progression of pre-existing HPV associated lesions or
      cancers have shown limited efficacy in eradicating established tumors in humans
      possibly due to examining patients with more advanced-stage cancer who tend to
      have decreased immune function. Future trends in clinical trials with therapeutic
      agents will examine patients with early stage cancers or pre-invasive lesions in
      order to prevent invasive cervical cancer. Meanwhile, preclinical studies in this
      field continue and include the further exploration of peptide or protein
      vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral
      vectors. Given that cervical cancers are caused by the human papillomavirus, the
      prospect of therapeutic vaccination to treat existing lesions and prophylactic
      vaccination to prevent persistent infection with the virus are high and may be
      implemented in the near future. The consequences for clinical management may
      include a significant reduction in the frequency of Pap smear screening in the
      case of prophylactic vaccines, and the availability of less invasive and
      disfiguring treatment options for women with pre-existing HPV associated lesions
      in the case of therapeutic vaccines. Implementation of both prophylactic and
      therapeutic vaccine regimens could result in a significant reduction of health
      care costs and reduction of worldwide cervical cancer incidence.

PMID- 15857017
TI  - FNAC: its role, limitations and perspective in the preoperative diagnosis of
      breast cancer.
AB  - Fine-needle aspiration cytology (FNAC) was first described and performed in 1930.
      Thirty years later, it gained acceptance first in Europe and about a decade later
      in North America. The method is generally considered as a rapid, reliable, safe
      diagnostic tool to distinguish non-neoplastic from neoplastic breast lesions. In
      developed countries, in the last 20 years, mammographic screening programmes,
      which have been used extensively, are designed to detect the earliest possible
      breast cancer. The FNAC report is extremely important because it gives the
      necessary information for the management of patients, in order to proceed with
      more invasive diagnostic methods or surgical treatment, and to decide what kind
      of operation to perform. In the preoperative phase, FNAC has taken a fundamental
      role of both palpable and nonpalpable lesions, using ultrasound or stereotactic
      guidance. New developed techniques, breast biopsy instrumentation (ABBI) and
      mammotome have the advantage of complete removal of breast lesions, but this is
      not possible in all the examined cases. In developing countries, economical
      restrictions, low budget for health care and screening programmes put the
      patients at a disadvantage because of the high cost of sophisticated diagnostic
      methods, thus we recommend that FNAC be used as a routine diagnostic method
      because of its low cost compared with the others and this policy maximizes the
      availability of health care to women with breast cancer. We conclude that FNAC
      plays an important and essential role in the management of patients with breast
      lesions and also offers a great potential for prediction of patient outcome,
      disease response to therapy and assessment of risk of developing breast cancer.
      The reliability and efficiency of the method depends on the quality of the
      samples and the experience of the medical staff that performs the aspiration.

PMID- 15857018
TI  - Management of massive presacral pelvic bleeding in patients with gynecological
      malignances: review of the literature.
AB  - Hemorrhage has always been a significant potential complication in the field of
      gynecological oncology. Throughout the years, a variety of medical and surgical
      modalities aimed at controlling pelvic hemorrhage have been developed. Most
      recently, these have focused on attempting to decrease the morbidity associated
      with pelvic bleeding. The effectiveness of and the complications involved in
      controlling massive hemorrhage by the preemptive method of vascular clamping of
      the aorta, intraoperative methods, such as the local application of procoagulants
      and of prolonged compression (pelvic gauze packing, plastic wrapped gauze
      packing, autograft tissue compression and balloon compression) have all been
      reviewed. Surgeons are able to acquaint themselves with the choice of methods
      that can be employed during massive pelvic bleeding resulting from procedures on
      gynecological malignancies.

PMID- 15857019
TI  - Thoracic metastases from breast cancer: a single-institution's experience.
AB  - OBJECTIVE: Thoracic metastasis from breast cancer (TMBC) is a relatively uncommon
      condition, and few reports of its therapeutic palliation and patient outcomes
      exist. We therefore reviewed retrospectively our radiotherapeutic experience of
      TMBC. METHODS: Between 1981 and 2003, 19 patients were treated with radiation
      (with doses raging from 10 Gy to 50 Gy) for palliation of TMBC. RESULTS: The mean
      age was 55.4 years. Mediastinal lymph node disease was the most common form of
      TMBC. TMBC developed within five years of breast cancer diagnoses in 11 patients
      (58%). Among the evaluable symptomatic individuals, subjective palliation was
      complete in 78% of the cases. The complete objective response (e.g., complete
      resolution of clinically manifested superior vena caval obstruction or imaging
      demonstrated atelectasis) rate was 50%. There was no significant difference in
      survival between patients presenting with airway obstruction and women who were
      not in respiratory distress, asymptomatic and symptomatic patients, and women
      with and without concurrent extrathoracic metastases. CONCLUSION: Although the
      prognosis of women with TMBC was quite ominous, radiotherapy should be considered
      in very symptomatic patients because justifiable palliation can be effected in
      some individuals.

PMID- 15857020
TI  - A case of metastasizing invasive hydatidiform mole. Is less--less good? Review of
      the literature with regard to adequate treatment.
AB  - BACKGROUND: Patients with invasive hydatidiform moles (IHM) have a good
      prognosis. Even if disease has spread, monocytostatic treatment might be
      sufficient if the diagnosis has been histologically confirmed. Established
      classifications divide gestational trophoblastic disease (GTD) including
      choriocarcinoma into cases with "high" and "low" risk. Without respect to
      histology "high-risk" cases are recommended to obtain polychemotherapy. CASE: A
      40-year-old nullipara underwent hysterectomy for persistent vaginal bleeding
      after she had already been treated with curettage for hydatidiform mole. An IHM
      was pathohistologically confirmed. There were no signs of pulmonary spread or
      other metastases at the time of surgery. Postsurgically persistent beta-hCG
      levels lead to thorough staging, which revealed multiple pulmonary metastases and
      a vaginal metastasis. Despite metastasizing GTD with poor prognosis criteria she
      was treated with single agent therapy. Eight cycles of two weekly methotrexate
      (MTX) were administered. All sites of metastases responded and our patient is
      still fine after one year of follow-up. CONCLUSION: With respect to this and
      other reports monochemotherapy can be a reasonable primary treatment for
      metastatic IHM.

PMID- 15857021
TI  - Primary breast lymphoma.
AB  - OBJECTIVES: Retrospective evaluation of the clinical behavior, treatment and
      prognosis in five cases of primary breast lymphoma. METHODS: From 1999 to 2003,
      five patients with primary breast lymphoma were diagnosed in our department.
      RESULTS: Primary breast lymphoma (PBL) was diagnosed in five patients, whose
      median age was 63.4 (41-79) years. In four out of five patients, a diagnosis of
      lymphoma was made after the evaluation of a palpable breast mass measuring 1.5 to
      6 cm. All of them were classified as non-Hodgkin's B cell lymphomas and three of
      five cases were diffuse large cell lymphomas. All patients were submitted to
      chemotherapy; in only one patient was surgery performed. CONCLUSIONS: A
      relatively high rate of PBL was observed in our department compared with other
      oncology centers. Beyond its scarce appearance, PBL is very difficult to
      distinguish from primary breast carcinoma. Histology remains the major diagnostic
      tool.

PMID- 15857022
TI  - Detection of axillary metastases in breast cancer patients using ultrasound and
      colour Doppler combined with fine needle aspiration cytology.
AB  - The aims of this study were to evaluate the diagnostic value of ultrasonography
      and colour Doppler combined with fine needle aspiration (FNA) cytology for the
      detection of non-palpable axillary lymph node metastases in breast cancer
      patients. Forty patients with operable breast cancer (T1/T2), invasive carcinoma,
      not submitted to neo-adjuvant therapy, underwent axillary ultrasonography and
      colour Doppler preoperatively. FNA cytology was performed on axillary lymph nodes
      presenting ultrasonographic and/or Doppler suspicious features. A total of 542
      lymph nodes were surgically removed from the 40 patients; 19 were metastatic
      lymph nodes. Ultrasound-guided FNA detected metastases in six out of 11
      histologically node-positive patients. Sensitivity and specificity in this
      preliminary study was 55% and 100%, respectively. These are the preliminary
      results of a prospective study that has the purpose of reducing the sentinel node
      procedures in breast cancer patients with clinically negative axillae, but
      positive FNA cytology.

PMID- 15857023
TI  - Lymph node pathway in the spread of endometrial carcinoma.
AB  - OBJECTIVE: To elucidate the sentinel nodes of endometrial carcinoma, the spread
      pathway was clarified. The correlation between lymph node spread and other
      clinicopathological variables was also analyzed. METHODS: Dissected lymph node
      samples in 342 patients who underwent pelvic and selective paraaortic
      lymphadenectomy were reviewed. Pelvic and paraaortic node (PLN and PAN) status
      was compared with clinicopathological parameters. RESULTS: Lymph node metastasis
      was demonstrated in 52 patients, including 46 cases with PLN metastasis and six
      patients with independent PAN metastasis. The metastatic sites were most frequent
      in the obturator and internal iliac nodes. Eleven of 49 patients who underwent
      PAN dissection were positive for metastasis. Sixteen of 23 cases with parametrial
      metastasis also metastasized in the retroperitoneal lymph node. CONCLUSION: The
      lymph node spread pathway in endometrial carcinoma consists of a major route via
      the obturator node or internal iliac node with or without parametrial
      involvement, and rarely a direct PAN pathway.

PMID- 15857024
TI  - Assessment of ER-alpha and ER-beta expression levels in malicious tumors of the
      uterine corpus.
AB  - PURPOSE: The purpose of this article is to present an assessment of the
      expression levels of estrogen receptors ER-alpha and ER-beta in malicious tumors
      of the uterine corpus. MATERIAL AND METHODS: Estrogen receptor expression levels
      were tested using semiquantitative immunohistochemical methods. Paraffin-embedded
      sections of tissue from the corpus of the uterus from 171 patients were used in
      the research. RESULTS: Analysis of the relation between ER-beta expression levels
      and the clinical grade of disease (based on FIGO classification) showed that
      these parameters are significantly related: p = 0.0099. There were no
      statistically significant relations between ER-alpha expression levels in tumors
      or clinical stages of tumors based on the FIGO criteria. The presence of high
      estrogen receptor beta expression levels is often accompanied by a low estrogen
      receptor alpha expression level and such arrangements allow the overt biological
      function of a dominant receptor. CONCLUSION: The differences in tissue
      distribution of both estrogen receptors could indicate their different biological
      roles.

PMID- 15857025
TI  - Effects of dioxin and nutrition on cellular proliferation and dioxin- and
      estrogen-linked genes in ovarian cancer cell lines.
AB  - This study was undertaken to examine the effects of dioxin (TCDD) and nutrition
      on cellular proliferation and dioxin- and estrogen-linked gene expression in
      ovarian cancer cell lines. Caov-3 and SK-OV-3 cells were incubated in a medium
      supplemented with 0.5-10% fetal bovine serum (FBS). Cell proliferation was
      assayed with an MTT assay. Dioxin- and estrogen-linked genes (AhR, ERalpha,
      ERbeta, CYP1A1 and ARNT) expressed were determined with the RT-PCR method. Caov-3
      cells, but not SK-OV-3 cells, were proliferated with TCDD alone with increased
      AhR and ERa mRNA expressions when incubated in the low FBS concentration. CYP1A1
      and ARNT mRNA expressions of SK-OV-3, but not that of Caov-3, were suppressed in
      the low FBS (under 1.0%) concentration. In the low FBS concentration medium with
      dioxin, AhR and ERa expression were increased with the proliferation of Caov-3
      cells; CYP1A1 and ARNT were stable. Each ovarian cancer cell line may have its
      own distinct responsiveness to dioxin depending on the nutritional state.

PMID- 15857026
TI  - Lymph node sampling is of prognostic value in early stage epithelial ovarian
      carcinoma.
AB  - PURPOSE: The importance of lymph node involvement as a prognostic factor is still
      under debate. In the present study, the impact of surgical staging for prognosis
      in early stages of epithelial ovarian cancer was evaluated in a series of 113
      patients. MATERIAL AND METHODS: A retrospective study was carried out at the
      Department of Gynecological Oncology, Orebro University Hospital, during the
      period 1994-1998. In a subgroup of 20 out of 113 patients, pelvic lymph node
      sampling or pelvic lymphadenectomy was included in the standard surgical
      procedure. In cases of positive lymph nodes, the tumors were upstaged to FIGO
      Stage III. Pearson's chi-square, the t-test, the log-rank test and Cox
      multivariate analysis were used in the statistical analyses. RESULTS: The 20
      patients with lymph node sampling or lymphadenectomy were compared with the
      remaining 93 patients without a comprehensive surgical staging procedure. A
      survival analysis demonstrated a significant (p = 0.005) difference in disease
      free survival rates between the two subgroups, where there was a survival benefit
      in the subgroup of patients who had undergone comprehensive surgical staging. In
      a Cox proportional hazard regression analysis with disease-free survival as the
      endpoint, high tumor grade (HR = 3.14) and comprehensive surgical staging with at
      least a node sampling (HR = 0.09) were significant and independent prognostic
      factors. CONCLUSION: The benefit in survival after the procedure of lymph node
      sampling in early stages of epithelial ovarian carcinoma could probably be
      explained by the fact that the surgical procedure detects otherwise unrecognized
      Stage III disease.

PMID- 15857027
TI  - Development of endometrial cancer following radiation therapy for cervical
      carcinoma.
AB  - The clinical and histologic findings in five cases of endometrial cancer, which
      developed following radiation therapy for squamous cell carcinoma of the cervix,
      are described. The mean age at endometrial cancer diagnosis was 69 years and
      average latency period from initial therapy to development of endometrial
      carcinoma was 13.4 years. For endometrial cancer, one patient had Stage Ib, one
      patient had Stage IIIa, two patients had Stage IIIc, and one patient did not
      undergo laparotomy. The histological types were carcinosarcoma in two patients,
      endometrioid adenocarcinoma, grade 3 in one patient, and clear cell carcinoma in
      one patient. All patients died of disease within 33 months of diagnosis.
      Endometrial cancers that develop after radiation treatment have a preponderance
      of high-risk histological subtypes, and consequently have a poor prognosis. Long
      term follow-up should be mandatory for patients surviving radiation therapy for
      cervical cancer in order to detect and effectively treat second malignancies.

PMID- 15857028
TI  - A retrospective study of 32 borderline ovarian tumours: the experience of a non
      specialized centre.
AB  - BACKGROUND: We evaluated the clinical features and treatment of patients with
      borderline ovarian tumors. METHODS: This was a retrospective review of the charts
      of 32 patients with borderline ovarian tumours that underwent surgery at the
      Department of Obstetrics and Gynaecology, Tzaneio General Hospital of Piraeus,
      over a 14-year period (1/1990-12/2003). RESULTS: Of the patients 62.5% were pre-
      or peri-menopausal. Mean age was 41.6 years. Five patients (15.63%) had undergone
      pelvic surgery (caesarean section not included) for unrelated reasons prior to
      the diagnosis of borderline tumour. Mean follow-up was 71.37 months and all
      patients showed up for their scheduled appointment during the first trimester of
      2004. Pain was the presenting symptom in 37.5% (12/32) of patients. Twenty
      patients were diagnosed either by ultrasound (12.5%, 4/32) or during unrelated
      surgeries (50%, 16/32) and reported no relevant symptoms at the time of
      diagnosis. Treatment was conservative, comprised of either cystectomy (3/32),
      unilateral salpingo-oophorectomy (13/32), and unilateral salpingo-oophorectomy
      with myomectomy (1/32). Abdominal hysterectomy with bilateral salpingo
      oophorectomy was performed in 15 patients for unrelated conditions (uterine
      pathology). Mucinous borderline tumours were identified in 11 patients (34.38%),
      serous borderline tumours in 17 patients (53.12%), and nonserous-mucinous
      borderline tumours in four patients (12.5%). Omentectomy was performed in two
      cases, biopsy of the controlateral ovary was performed in five cases and
      peritoneal washing in eight cases. Restaging surgery was performed at the Metaxa
      Anticancer Piraeus Hospital in 11 patients (34.38%). One patient who did not
      undergo a restaging operation had a recurrence of the disease. CONCLUSION:
      Suboptimal staging remains a major problem during the initial operation in non
      specialized centres in gynaecologic malignancies.

PMID- 15857029
TI  - Expression of matrix metalloproteinase-2 in preinvasive and invasive carcinoma of
      the uterine cervix.
AB  - PURPOSE: To study the immunohistochemical expression of matrix metalloproteinase
      2 (MMP-2) in preinvasive and invasive carcinoma of the uterine cervix so as to
      demonstrate whether the expression of MMP-2 is an early or late event in the
      process of dedifferentiation and cancer progression. METHODS: A total number of
      50 samples of cervical tissue were studied for MMP-2 immunoreactivity. The cases
      were selected to include ten normal cases used as a control group, 20 CIN cases
      and 20 cervical carcinoma cases. The CIN group was subdivided into CIN1 (n = 7),
      CIN2 (n = 6) and CIN3 (n = 7), while the carcinoma group was represented by
      squamous cell carcinoma (n = 16) and adenocarcinoma (n = 4). RESULTS: MMP-2
      expression was totally absent in control cervices and low-grade squamous
      intraepithelial lesions, while high-grade squamous intraepithelial neoplasia and
      invasive carcinoma showed up-regulation of MMP-2 expression with no significant
      difference concerning the type of carcinoma. This overexpression of MMP-2 points
      to the possibility that it is an early marker of tumor progression in cervical
      carcinoma. CONCLUSIONS: MMP-2 has a key role in extracellular matrix degradation
      and invasion in carcinoma of the uterine cervix. Its expression in high-grade
      squamous intraepithelial lesions may denote a potential risk for invasion and
      metastasis.

PMID- 15857030
TI  - Effect of hysterosalpingography on serum cancer antigen (CA-125) levels.
AB  - OBJECTIVE: The aim of our study was to detect any rise in serum levels of CA-125
      after hysterosalpingography (HSG) as a result of irritation of the peritoneum.
      STUDY DESIGN: Serum levels of CA-125 were assessed before HSG and at the 2nd and
      6th hours after HSG in 32 infertile patients who were admitted to our clinic from
      April 2002 to September 2002. Patients who showed tubal occlusion or Asherman
      Syndrome were excluded from the study. The levels of serum CA-125 were compared
      statistically. Statistical analysis was performed with SPSS 10.0 statistical
      software and the paired-sample t-test was applied. RESULTS: The mean levels of
      serum CA-125 before HSG, and at the 2nd and 6th hours after HSG were; 14.11 +/-
      5.97 mIU/ml, 13.96 +/- 5.80 mIU/ml, and 14.06 +/- 5.80 mIU/ml, respectively.
      There was no statistically significant difference between serum levels of CA-125
      before HSG and at the 2nd or 6th hours after HSG, and also between the 2nd and
      6th hours after HSG (p > 0.05). CONCLUSION: We have not found any reports up to
      date about the levels of serum CA-125 after HSG. In our study we did not detect
      any increase in levels of serum CA-125 at the 2nd and 6th hours after HSG in
      spite of peritoneal irritation. We propose that this finding is because leakage
      of radioopaque material to the abdominal cavity is minimal during the HSG
      procedure.

PMID- 15857031
TI  - BRCA1 mutation, leptin and estrogen levels in breast cancer patients.
AB  - Pre- and postmenopausal patients with breast cancer were screened for mutation of
      the BRCAI gene and estrogens and leptin levels were measured. In postmenopausal
      BRCA1 mutation carriers, leptin levels were significantly lower and correlated
      with the body mass index (BMI). No significant difference in leptin levels was
      revealed between pre- and postmenopausal patients. Our findings suggest the
      existence of an alternative mechanism responsible for carcinogenesis in breast
      cancer patients with a genetic background.

PMID- 15857032
TI  - Epidemiology of hydatidiform mole in Finland, 1975 to 2001.
AB  - PURPOSE: Broad variations in the incidence of gestational trophoblastic diseases
      have been reported in different parts of the world. Recent time trends in the
      incidence of hydatidiform mole in Western countries have not been elucidated. We
      studied the epidemiology of hydatidiform mole in Finland over a period of 27
      years. METHODS: Women reported to have hydatidiform mole from 1975-2001 were
      identified from the National Research and Development Center for Welfare and
      Health. Women with choriocarcinoma were identified from the Finnish Cancer
      Registry. RESULTS: We identified 1659 cases of hydatidiform mole between 1975 and
      2001. This gives an incidence of 73/10(6) women or 984/10(6) deliveries. The
      overall incidence remained fairly constant over the study period. The incidence
      was higher in women below 20 years and above 39 years than in women in the other
      age groups. Forty-nine percent of choriocarcinomas identified during the study
      period were associated with a preceding hydatidiform mole. The risk of
      choriocarcinoma after a hydatidiform mole was 2.2%. CONCLUSIONS: The incidence of
      hydatidiform mole in Finland follows the same patterns as in other Western
      countries. The incidence has not changed considerably in recent decades.

PMID- 15857033
TI  - Differentiation of benign and malignant adnexal masses: value of a morphologic
      scoring system.
AB  - OBJECTIVE: The purpose of this study was to assess the value of conventional gray
      scale ultrasonography, based on a morphologic scoring system, in the differential
      diagnosis of malignant and benign adnexal tumors. MATERIAL AND METHODS: A total
      of 58 adnexal masses in 51 patients were classified prospectively as suggestive
      of malignant or benign, on the basis of gray-scale ultrasonographic morphology.
      The results were correlated with histopathological diagnosis. RESULTS:
      Histopathology of 42 masses was found to be benign and 16 masses were found to be
      malignant. On gray-scale analysis 15 of 16 malignant masses were classified as
      suggestive of malignant and 37 of 42 benign masses were classified as suggestive
      of benign. The sensitivity, specificity, positive predictive value and negative
      predictive value are calculated as 93%, 88%, 75%, and 97%, respectively.
      CONCLUSION: Prediction of malignancy using gray scale ultrasonograhy based on a
      morphological scoring system was reliable (NPV = 97%, PPV = 93%). However further
      investigations about the assessment of adnexal masses with ultrasonography are
      needed

PMID- 15857034
TI  - Mondor's disease of the breast: is there any relation to breast cancer?
AB  - Ten cases of Mondor's disease of the breast (9 females, 1 male) are described.
      The diagnosis was based mainly on clinical examination, while breast imaging,
      used in five cases, was complementary. Most of our cases (9) had complete
      restoration of the thrombosed subcutaneous breast vein, either spontaneously (4),
      or after anti-inflammatory medication (5). Only one of our patients had surgical
      management (vein excision) due to delayed remission. None of our cases was
      related to breast cancer.

PMID- 15857035
TI  - Cytological analysis of the distension fluid used during diagnostic office
      hysteroscopies in patients with suspected endometrial pathology.
AB  - OBJECTIVE: Evaluation of the feasibility and usefulness of cytological analysis
      of the distension fluid used during diagnostic office hysteroscopy in patients
      with suspected endometrial pathology. METHODS: In 243 consecutive patients
      undergoing diagnostic hysteroscopy for suspected endometrial pathology a few
      milliliters of the distension medium used for uterine visualization were
      collected and sent for cytological analysis. Findings of these "endometrial
      washings" were compared to visual hysteroscopic impression, endometrial biopsy
      and uterine histology--when available. RESULTS: Endometrial washings were
      considered adequate in 227 patients (93.4%). In 12 cases (5.3%) atypical cells
      were detected: all of these presented either atypical complex hyperplasia or
      endometrial cancer at the final histological evaluation of the uterus. Four of
      the 16 (25%) patients diagnosed with endometrial cancer or atypical complex
      hyperplasia at the final histopathological analysis of the uterus had inadequate
      washings. No patient with cancer or atypical hyperplasia had negative cytology.
      CONCLUSIONS: Collection and analysis of the distension fluid is feasible and,
      when positive, has a remarkable value in the diagnosis of endometrial cancer and
      its precursors.

PMID- 15857036
TI  - Pelvic retroperitoneal paraganglioma mimicking an ovarian mass.
AB  - A 75-year-old hypertensive woman was referred with ultrasound findings of a 40 x
      35 mm semi-solid right adnexal mass and right hydroureteronephrosis. She
      complained of headache and right-sided back pain. Computed tomography
      demonstrated a cystic adnexal mass that did not appear to originate from the
      right ovary and grade 2 hydroureteronephrosis. Magnetic resonance imaging
      indicated that the mass originated from the right ovary. Tumor markers were in
      the normal range. Exploratory laparotomy was performed to determine the origin of
      the lesion, and revealed a retroperitoneal mass obstructing the right ureter. The
      mass was completely removed and and the histopathologic diagnosis was
      paraganglioma.

PMID- 15857037
TI  - Pancreatic tumor in a pregnant woman: a rare case report.
AB  - We have analyzed a case of pancreatic carcinoma in a pregnant woman, 37 years
      old, in the second trimester of the pregnancy. She had a positive family history
      of digestive tract carcinoma. The delivery ended surgically and hysterectomy was
      performed at the same time.

PMID- 15857038
TI  - Primary carcinoma of the fallopian tube mimicking tubo-ovarian abscess.
AB  - PURPOSE: The aim of the study is to report that the primary fallopian tube cancer
      can be presented as a tubo-ovarian abscess preoperatively. METHODS: A patient
      with a preoperative diagnosis of a tubo-ovarian abscess with abdominal pain,
      tenderness and an elevated fever with leukocytes underwent urgent exploratory
      laparotomy. RESULTS: Explorative laparotomy and accompanied frozen section
      revealed a right-sided tubal carcinoma. There was an inflammatory and purulent
      reaction in the tube that was adherent to the anterior uterus. Total hysterectomy
      and bilateral salpingo-oophorectomy were performed. CONCLUSION: Carcinoma of the
      fallopian tube should be considered in the differential diagnosis of acute pelvic
      peritonitis like a tubo-ovarian abscess.

PMID- 15857039
TI  - Verrucous carcinoma of the cervix--diagnostic and therapeutic difficulties with
      regards to HPV status. Case report.
AB  - Verrucous carcinoma of the cervix is of special interest because of its rare
      occurrence and frequently existing difficulties in the differential diagnosis,
      which in verrucous disease eventually leads to a final, more favorable diagnosis.
      We present a case report of cervical verrucous carcinoma as a rare variant of
      squamous cell carcinoma in a 65-year-old woman who underwent total hysterectomy
      based on initial histological diagnosis of cervical dysplasia. Special attention
      is focused on clinical assessment of the lesion with the depicted restriction of
      exfoliated cytology as well as misdiagnoses of inappropriately taken, even
      colposcopically directed biopsy, not covering a full thickness of biopsied
      tissue. The macro- and micromorphologic similarities of cervical verrucous
      carcinoma with condylomata acuminata on one hand and invasive squamous cell
      carcinoma on the other, inclined us to search for a common factor causing human
      papillomavirus infection.

PMID- 15857040
TI  - A case of ovarian sarcoidosis mimicking malignancy.
AB  - We present a case of systemic sarcoidosis with ovarian and peritoneal
      involvement. The atypical clinical presentation of the disease has lead to a
      problem of the differential diagnosis with ovarian cancer. A 72-year-old female
      was admitted because of low grade fever, fatigue and dilatation of the abdomen.
      Clinical and laboratory evaluation of the patient revealed moderate right pleural
      effusion, ascites, diffuse ovarian infiltration, presence of enlarged
      intraabdominal lymph nodes and a substantially high value of serum CA 125.
      Histological examination after laparotomy was indicative of ovarian sarcoidosis.

PMID- 15857041
TI  - The use of thumbtacks to stop severe presacral bleeding.
AB  - Massive presacral bleeding arising during gynaecological surgery can be sudden,
      rapid and life-threatening. Further, its control and management can be
      challenging, since standard measures are frequently ineffective. The use of
      thumbtacks to control severe presacral venous haemorrhage was first reported in
      1985. Despite this, it does not appear to be widely known or used in
      gynaecological surgery. A case is presented in which the technique was used, and
      the literature on its use is reviewed.

PMID- 15857042
TI  - Fabrication and characterization of micromachined high-frequency tonpilz
      transducers derived by PZT thick films.
AB  - Miniaturized tonpilz transducers are potentially useful for ultrasonic imaging in
      the 10 to 100 MHz frequency range due to their higher efficiency and output
      capabilities. In this work, 4 to 10-microm thick piezoelectric thin films were
      used as the active element in the construction of miniaturized tonpilz
      structures. The tonpilz stack consisted of silver/lead zirconate titanate
      (PZT)/lanthanum nickelate (LaNiO3)/silicon on insulator (SOI) substrates. First,
      conductive LaNiO3 thin films, approximately 300 nm in thickness, were grown on
      SOI substrates by a metalorganic decomposition (MOD) method. The room temperature
      resistivity of the LaNiO3 was 6.5 x 10(-6) omega x m. Randomly oriented PZT
      (52/48) films up to 7-microm thick were then deposited using a sol-gel process on
      the LaNiO3-coated SOI substrates. The PZT films with LaNiO3 bottom electrodes
      showed good dielectric and ferroelectric properties. The relative dielectric
      permittivity (at 1 kHz) was about 1030. The remanent polarization of PZT films
      was larger than 26 microC/cm2. The effective transverse piezoelectric e31,f
      coefficient of PZT thick films was about -6.5 C/m2 when poled at -75 kV/cm for 15
      minutes at room temperature. Enhanced piezoelectric properties were obtained on
      poling the PZT films at higher temperatures. A silver layer about 40-microm thick
      was prepared by silver powder dispersed in epoxy and deposited onto the PZT film
      to form the tail mass of the tonpilz structure. The top layers of this wafer were
      subsequently diced with a saw, and the structure was bonded to a second wafer.
      The original silicon carrier wafer was polished and etched using a Xenon
      difluoride (XeF2) etching system. The resulting structures showed good
      piezoelectric activity. This process flow should enable integration of the
      piezoelectric elements with drive/receive electronics.

PMID- 15857043
TI  - Free vibrations of an electroelastic body under biasing fields.
AB  - We present a systematic analysis of the eigen-value problem associated with free,
      small-amplitude vibrations superposed on finite biasing fields in an
      electroelastic body. An abstract formulation is introduced. The operators in the
      abstract formulation are shown to be self-adjoint, from which a series of
      fundamental properties of resonant frequencies and modes are proved concisely. A
      variational formulation and a perturbation analysis of the eigenvalue problem
      also are given based on the abstract formulation.

PMID- 15857044
TI  - Temperature effect on the bandgaps of surface and bulk acoustic waves in two
      dimensional phononic crystals.
AB  - In this paper, we analyzed the temperature effect on two-dimensional phononic
      crystals. Bandgap variations of both of the bulk modes and surface modes due to
      changing of temperature in an air/quartz band structure from 0 to 50 degrees C
      were calculated and discussed. The results show that the elastic bandgaps can be
      enlarged or reduced by adjusting the temperature of the band structure. The
      temperature effects potentially can be used for fine-tuning of the phononic
      bandgap frequency.

PMID- 15857045
TI  - Finite-difference, time-domain analysis of a folded acoustic transmission line.
AB  - Recently designed, modern versions of renais sance woodwind instruments such as
      the recorder and serpent use square cross sections and a folded acoustic
      transmission line. Conventional microwave techniques would expect that this bend
      would cause unwanted reflections and impedance discontinuities. This paper
      analyses the folded acoustic transmission line using finite-difference, time
      domain techniques and shows that the discontinuity can be compensated with by the
      use of a manufacturable method.

PMID- 15857046
TI  - Development and evaluation of a high-frequency ultrasound-based system for in
      vivo strain imaging of the skin.
AB  - The elastic properties of skin are of great interest in dermatology because they
      are affected by many pathological conditions. In this paper, a technique for in
      vivo mechanical strain imaging of the skin based on high-frequency ultrasound
      (HFUS) is presented. Elastic skin properties are assessed applying suction to the
      skin surface with a stepwise increased vacuum and estimating the resulting
      displacements in a spatially resolved manner. Acquired radio frequency (RF) echo
      signals and their envelope are analyzed for this purpose. A computer-controlled
      vacuum system with a digital pressure control loop was developed for precise and
      reproducible deformation. In a first processing step, the skin surface is
      segmented. Local axial strains inside the skin are estimated from axial
      displacements, which are estimated from consecutive echo signal frames analyzing
      the phase of the complex cross correlation function of analytical echo signals.
      Furthermore, speckle tracking is applied to estimate axial and lateral
      displacements and to quantify axial and lateral strains. The correlation
      coefficient of windowed echo signals compensated for displacements are used as a
      measure to validate the estimated strains, which is essential to accomplish
      reliable in vivo measurements. Phantom experiments were performed to validate the
      proposed technique. Results of in vivo measurements are presented, showing the
      potential for mechanical strain imaging in the skin in vivo.

PMID- 15857047
TI  - Determination of an optimal image frame interval for frame-to-frame ultrasound
      image motion tracking.
AB  - Several important clinical applications depend on accurate ultrasound image frame
      to-frame motion estimation. Assuming that there is a degree of finite noise in
      the image frames and that speckle partially decorrelates between successive
      frames during freehand scanning, we hypothesize that an optimal inter-frame
      interval (step size) must exist that provides the smallest relative dimensional
      error over a set of accumulated motion estimates. Smaller frame increments suffer
      from less decorrelation-related inaccuracy but present greater potential for
      cumulative error because more estimates are used over any specific dimensional
      interval. We studied these effects using a combination of theoretical modeling,
      numerical simulation, and experiments. Components of diagonal motion due to the
      limitations of manual transducer movement were considered as the cause of
      decorrelation. The results were examined for four different angles of the
      diagonal motion and two different signal-to-noise ratio (SNR) values. These
      indicate that an optimal step size does exist and that this is dependent on many
      variables including SNR, angle of the diagonal motion, transducer geometry, lens
      focusing parameters, transducer operating frequency, and beamforming parameters.
      In practical experiments, we found that the optimal step size generally required
      using every available image frame rather than 'skipping' any intermediate frames.

PMID- 15857048
TI  - A full-wave Helmholtz model for continuous-wave ultrasound transmission.
AB  - A full-wave Helmholtz model of continuous-wave (CW) ultrasound fields may offer
      several attractive features over widely used partial-wave approximations. For
      example, many full-wave techniques can be easily adjusted for complex geometries,
      and multiple reflections of sound are automatically taken into account in the
      model. To date, however, the full-wave modeling of CW fields in general 3D
      geometries has been avoided due to the large computational cost associated with
      the numerical approximation of the Helmholtz equation. Recent developments in
      computing capacity together with improvements in finite element type modeling
      techniques are making possible wave simulations in 3D geometries which reach over
      tens of wavelengths. The aim of this study is to investigate the feasibility of a
      full-wave solution of the 3D Helmholtz equation for modeling of continuous-wave
      ultrasound fields in an inhomogeneous medium. The numerical approximation of the
      Helmholtz equation is computed using the ultraweak variational formulation (UWVF)
      method. In addition, an inverse problem technique is utilized to reconstruct the
      velocity distribution on the transducer which is used to model the sound source
      in the UWVF scheme. The modeling method is verified by comparing simulated and
      measured fields in the case of transmission of 531 kHz CW fields through layered
      plastic plates. The comparison shows a reasonable agreement between simulations
      and measurements at low angles of incidence but, due to mode conversion, the
      Helmholtz model becomes insufficient for simulating ultrasound fields in plates
      at large angles of incidence.

PMID- 15857049
TI  - Identification of ultrasound contrast agent dilution systems for ejection
      fraction measurements.
AB  - Left ventricular ejection fraction is an important cardiac-efficiency measure.
      Standard estimations are based on geometric analysis and modeling; they require
      time and experienced cardiologists. Alternative methods make use of indicator
      dilutions, but they are invasive due to the need for catheterization. This study
      presents a new minimally invasive indicator dilution technique for ejection
      fraction quantification. It is based on a peripheral injection of an ultrasound
      contrast agent bolus. Left atrium and left ventricle acoustic intensities are
      recorded versus time by transthoracic echocardiography. The measured curves are
      corrected for attenuation distortion and processed by an adaptive Wiener
      deconvolution algorithm for the estimation of the left ventricle impulse
      response, which is interpolated by a monocompartment exponential model for the
      ejection fraction assessment. This technique measures forward ejection fraction,
      which excludes regurgitant volumes. The feasibility of the method was tested on a
      group of 20 patients with left ventricular ejection fractions going from 10% to
      70%. The results are promising and show a 0.93 correlation coefficient with
      echographic bi-plane ejection fraction measurements. A more extensive validation
      as well as an investigation on the method applicability for valve insufficiency
      and right ventricular ejection fraction quantification will be an object of
      future study.

PMID- 15857050
TI  - Acoustic radiation force enhances targeted delivery of ultrasound contrast
      microbubbles: in vitro verification.
AB  - Recent research has shown that targeted ultrasound contrast microbubbles achieve
      specific adhesion to regions of intravascular pathology, but not in areas of high
      flow. It has been suggested that acoustic radiation can be used to force free
      stream microbubbles toward the target, but this has not been verified for actual
      targeted contrast agents. We present evidence that acoustic radiation indeed
      increases the specific targeted accumulation of microbubbles. Lipid microbubbles
      bearing an antibody as a targeting ligand were infused through a microcapillary
      flow chamber coated with P-selectin as the target protein. A 2.0 MHz ultrasonic
      pulse was applied perpendicular to the flow direction. Microbubble accumulation
      was observed on the flow chamber surface opposite the transducer. An acoustic
      pressure of 122 kPa enhanced microbubble adhesion up to 60-fold in a microbubble
      concentration range of 0.25 x 10(6) to 75 x 106) ml(-1). Acoustic pressure
      mediated the greatest adhesion enhancement at concentrations within the clinical
      dosing range. Acoustic pressure enhanced targeting nearly 80-fold at a wall shear
      rate of 1244 s(-1), suggesting that this mechanism is appropriate for achieving
      targeted microbubble delivery in high-flow vessels. Microbubble adhesion
      increased with the square of acoustic pressure between 25 and 122 kPa, and
      decreased substantially at higher pressures.

PMID- 15857051
TI  - Considerations in the design and sensitivity optimization of the micro tactile
      sensor.
AB  - Although miniaturization has been considered the only technology with which to
      increase sensitivity of tactile sensors, we recently developed the micro tactile
      sensor (MTS) that performs with high sensitivity without microfabrication. In
      this study, we examined design and sensitivity optimization of the MTS using
      theory based upon Mason's equivalent circuit. The touch probe, which is attached
      to the lead zirconate titanate (PZT) element, was expressed as a purely inductive
      circuit component. Resonance frequency was calculated as a function of the length
      of the touch probe, and sensitivity was predicted to be dependent on the length.
      Furthermore, many kinds of MTS were fabricated with different touch probe
      lengths, and actual sensitivity was measured as phase shift between nonloaded and
      loaded conditions. And, from the consideration of theory and experimental data, a
      sensitivity coefficient was proposed and found to be useful.

PMID- 15857052
TI  - Remote sensing of mechanical properties of materials using a novel ultrasound
      transducer and signal processing.
AB  - An ultrasound-based remote sensing method to evaluate the mechanical properties
      of materials is presented. This method consists of a disk-shaped, piezoelectric
      transducer, operating at its resonance frequency, and a phase-shifted, feedback
      circuit. Mechanical parameters are derived by analyzing the signal contained in
      the phase-shifted values of the reflected signal. It is concluded that, using
      this novel transducer system and signal processing, remote mechanical
      measurements can be made. Such measurements obviate the need to apply the force
      deformation approach and may be used to enable stiffness imaging.

PMID- 15857053
TI  - A study of crosstalk effects on the packaged SAW by the FDTD method.
AB  - The purpose of this study is to estimate the complete crosstalk effects,
      including the package and the pads on the surface acoustic wave (SAW) substrate.
      The coupling influence from the SAW pattern is investigated by the full-wave
      approach. In order to combine the electromagnetic effects with the surface
      acoustic wave response, a new approach based on finite difference time domain
      (FDTD) with equivalent current source method is applied. The resistive voltage
      source model is carefully used to simulate the situations of measurement by the
      vector network analyzer more accurately. Two kinds of patterns of one-port SAW
      resonators with the same package structure and interdigital transducer (IDT)
      design are studied. From the simulated electromagnetic field distributions over
      the substrate, it can be seen that, as the pattern on the SAW substrate becomes
      closer, more input energy will be coupled directly to the parallel pads by
      crosstalk without filtering. This will lead to more coupling loss and, therefore,
      the insertion loss becomes universally lower by about 2 to 3 dB. Furthermore, it
      can be observed that the coupling interference from the SAW pattern is more
      serious than from the package in this case. Verification with the measurement
      results shows that our method is able to obtain good agreement and can be used to
      observe the influence from the SAW pattern that can seriously affect the
      performance of the SAW device.

PMID- 15857054
TI  - Piezoelectric micromachined ultrasonic transducers: modeling the influence of
      structural parameters on device performance.
AB  - Piezoelectric micromachined ultrasonic transducers (pMUTs), a potential
      alternative for conventional one-dimensional phased array ultrasonic transducers,
      were investigated. We used a modeling approach to study the performance of lead
      zirconate titanate (PZT)-driven pMUTs for the frequency range of 2-10 MHz,
      optimized for maximum coupling coefficient, as a function of device design. Using
      original tools designed for the purpose, a comprehensive build-test finite
      element model was developed to predict and measure the device performance. In
      particular, the model estimates the device coupling coefficient and the acoustic
      impedance, besides the readily extractable resonance frequency and bandwidth. To
      validate the model, a prototype device was built and tested, showing good
      agreement between the model predictions and experimental results. Modeling
      results indicate that the coupling coefficient is significantly affected by
      silicon membrane, PZT, and top electrode thickness as well as the top electrode
      design. Results also indicate considerable flexibility in maximizing the coupling
      coefficient while maintaining the device acoustic impedance at a level matching
      that of the human body. The bandwidth proved to be superior to that of
      conventional transducers, reaching 102% in some cases.

PMID- 15857055
TI  - An analytical model of multilayer ultrasonic transducers with an inversion layer.
AB  - Inversion layer ultrasonic transducers have been investigated recently as an
      interesting approach in wideband transducer design. In this paper we present an
      analytical model of multilayer ultrasonic transducers with an inversion layer.
      Our analysis of the wave propagation problem of an inversion layer transducer
      includes a functional decomposition of the electrical input impedance. It becomes
      clear from this decomposition that an inversion layer transducer can be modeled
      as three elements in series connection, i.e., a clamped capacitance, a classical
      motional impedance, and a coupled motional impedance. The first two elements make
      up the classical model of a single element transducer. The coupled motional
      impedance describes the coupled interaction between the regular and the inverted
      piezoelectric sublayers, and thus reflects the effect of an inversion layer. We
      present examples which show that inversion layer transducers are advantageous in
      achieving such useful features as dual-frequency operation mode as used in
      harmonic imaging or broadband performance desired in most ultrasonic
      applications.

PMID- 15857056
TI  - Applying Taguchi dynamic characteristics to the robust design of a piezoelectric
      sensor.
AB  - It is important that measurement systems provide an accurate and robust
      performance over a wide range of input conditions. Under these conditions, the
      measurement system is said to have a robust design with dynamic characteristics.
      This paper adopts Taguchi's signal-to-noise ratio analysis to optimize the
      dynamic characteristics of a piezoelectric gas sensor system whose output
      response is linearly related to the input signal. The goal of the present dynamic
      characteristics study is to increase the sensitivity of the measurement system
      while simultaneously reducing its variability. This study focuses upon the
      conventional quartz crystal nanobalance (QCN) gas sensor. A time- and cost
      efficient finite element analysis method is utilized to investigate the effects
      of the deposited mass upon the resonant frequency output of the QCN biosensor.

PMID- 15857057
TI  - Spurious suppression of a microstrip bandpass filter using three types of
      rectangular PBG loops.
AB  - A novel microstrip bandpass filter with three types of rectangular, photonic
      bandgap (PBG) loops on a middle layer was designed and demonstrated using a full
      wave electromagnetic (EM) simulator, with the predicted results verified by
      experiment. This investigation presents the configurations of conventional
      parallel-coupled 2 GHz filters with and without a PBG. The middle-layer of PBG
      loops adds an extra stopband-rejection mode to filter stopband; and it provides
      attenuation in excess of 25 dB at the second, third, and fourth harmonics, thus
      demonstrating that superior stopband characteristics at high frequency can be
      obtained using the proposed PBG loops in microwave filters.

PMID- 15857058
TI  - Application of the Schlieren pulsed method for the observation of simple and
      multiple scattering of ultrasonic waves.
AB  - The Schlieren pulsed method uses short-term lighting triggered by an acoustic
      pulse. This allows for an observation of elastic deformation fields in pulsed
      regime and for an evaluation of the evolution of the pulse in the interior of
      homogenous and heterogeneous media. In this paper we apply the Schlieren pulsed
      method to determine the conditions of the change from simple to multiple
      scattering. An ultrasound transducer put in water emits a wide-band pulse. The
      pulse goes through a region of parallel cylindrical wires, uniformly spaced and
      perpendicular to the acoustic beam. Varying the width of the zone of the
      scatterer cylinders, it is possible to optically observe the transmitted acoustic
      field and to calculate the transmission coefficient. By studying the behavior of
      this coefficient in function of the medium width, we obtained the zone in which
      the transition between simple and multiple scattering happens.

PMID- 15857059
TI  - High-frequency, nonlinear flow imaging of microbubble contrast agents.
AB  - It has been shown that nonlinear scattering can be stimulated from microbubble
      contrast agents at high-transmit frequencies (14-32 MHz). This work was extended
      to demonstrate the feasibility of nonlinear contrast imaging through
      modifications of existing ultrasound biomicroscopy linear B-scan imaging
      instrumentation. In this study, we describe the development and evaluation of
      prototype coherent flow imaging instrumentation for nonlinear microbubble imaging
      using transmit frequencies from 10 to 50 MHz. Phantom validation experiments were
      conducted to demonstrate color and power flow imaging using nonlinear 10 MHz
      (subharmonic) scattering induced by a 20 MHz transmit frequency. In vivo flow
      imaging of a rabbit ear microvessel was successfully performed. This work
      indicates the feasibility of performing flow imaging at high frequencies using
      nonlinear scattering from microbubbles.

PMID- 15857060
TI  - Surface acoustic wave properties of proton-exchanged LiNbO3 waveguides with SiO2
      film.
AB  - Surface acoustic wave (SAW) properties of proton-exchanged (PE) z-cut lithium
      niobate (LiNbO3) waveguides with silicon dioxide (SiO2) film layers were
      investigated using octanoic acid. The distribution of hydrogen measured by
      secondary ion mass spectrometry (SIMS) showed a step-like profile, which was
      assumed to be equal to the waveguide depth (d). The SiO2 film was deposited on z
      cut LiNbO3 waveguide by radio frequency (rf) magnetron sputtering. We
      investigated the important parameters for the design of SAW devices such as phase
      velocity (Vp), insertion loss (IL) and temperature coefficient of frequency (TCF)
      by a network analyzer using thin-film aluminum interdigital transducer electrodes
      on the upper SiO2 film surface. The experimental results showed that the Vp of
      SAW decreased slightly with the increase of h/lambda, where h was the thickness
      of SiO2 films and lambda was the wavelength. The IL of SAW increased with
      increased h/lambda. The TCF of SAW calculated from the frequency change of the
      output of SAW delay line showed an evident decrease with the increase of
      h/lambda. The TCF for PE z-cut LiNbO3 was measured to be about -54.72
      ppm/degreees C at h/lambda = 0.08. It revealed that the SiO2 films could
      compensate and improve the temperature stability as compared with the TCF of SAW
      on PE samples without SiO2 film.

PMID- 15857061
TI  - Fourteen-year incidence of age-related maculopathy and cause-specific prevalence
      of visual impairment and blindness in a Caucasian population: the Copenhagen City
      Eye Study.

PMID- 15857063
TI  - Effects of activated platelet concentrates on human primary cultures of
      fibroblasts and osteoblasts.
AB  - BACKGROUND: Platelet alpha granules contain growth factors released into the
      surrounding environment during activation. This property has been used in
      clinical medicine to accelerate the repair process by activating in vitro
      autologous platelets with thrombin and has also been proposed to promote the
      proliferation of bone cells. The aim of this research was to assess the effect of
      platelet concentrates activated with thrombin on human gingival fibroblasts and
      human osteoblasts from trabecular bone. METHODS: Platelet concentrates, activated
      with bovine thrombin, were added to the cells in serum-free medium. The cultures
      were assessed for proliferation by vital stain and cell count after 72-hour
      incubation. Alkaline phosphatase activity was tested after 72-hour incubation on
      the osteoblast lysates by a colorimetric assay. After 21 days the formation of
      mineral nodules was tested in the osteoblast cultures by alizarin red staining.
      The effects of the activated platelet concentrates (APC) were compared with the
      serum-free medium (SF), or with platelet-poor plasma added medium (PPP). RESULTS:
      The fibroblast growth in the presence of APC was higher, though not
      significantly, than SF. APC resulted in a nonsignificant decrease in
      proliferation and alkaline phosphatase expression in osteoblasts, compared both
      to serum free medium, and PPP. Mineralization was only modestly increased after
      incubation with APC in comparison with serum-free medium. CONCLUSIONS: There were
      no statistical differences in fibroblast proliferation, or in osteoblast growth
      and functions between serum-free conditions and the platelet gel treatment.
      Therefore, neither fibroblast proliferation nor osteoblast growth and functions
      were affected by the activated platelet concentrates in vitro.

PMID- 15857064
TI  - Post-surgical infections: prevalence associated with various periodontal surgical
      procedures.
AB  - BACKGROUND: Of the various adverse outcomes that may be encountered following
      periodontal surgery, the risk of infection stands at the forefront of concern to
      the surgeon, since infection can lead to morbidity and poor healing outcomes.
      This paper describes a large-scale retrospective study of multiple surgical
      modalities in a diverse periodontal practice undertaken to explore the prevalence
      of clinical infections post-surgically and the relationship between diverse
      treatment variables and infection rates. METHODS: A retrospective review of all
      available periodontal surgical records of patients treated in the Department of
      Periodontics at Wilford Hall Medical Center, San Antonio, Texas, was conducted.
      The sample comprised 395 patients and included 1,053 fully documented surgical
      procedures. Surgical techniques reviewed included osseous resective surgery, flap
      curettage, distal wedge procedures, gingivectomy, root resection, guided tissue
      regeneration, dental implant surgery, epithelialized free soft tissue autografts,
      subepithelial connective tissue autografts, coronally positioned flaps, sinus
      augmentations, and ridge preservation or augmentation procedures. Infection was
      defined as increasing and progressive swelling with the presence of suppuration.
      The impact of various treatment variables was examined including the use of bone
      grafts, membranes, soft tissue grafts, post-surgical chlorhexidine rinses,
      systemic antibiotics, and dressings. Results were analyzed using Fisher's exact
      test and Pearson's chi-square test. RESULTS: Of the 1,053 surgical procedures
      evaluated in this study, there were a total of 22 infections for an overall
      prevalence of 2.09%. Patients who received antibiotics as part of the surgical
      protocol (pre- and/ or post-surgically) developed eight infections in 281
      procedures (2.85%) compared to 14 infections in 772 procedures (1.81%) where
      antibiotics were not used. Procedures in which chlorhexidine was used during post
      surgical care had a lower infection rate (17 infections in 900 procedures, 1.89%)
      compared to procedures after which chlorhexidine was not used as part of post
      surgical care (five infections in 153 procedures, 3.27%). The use of a post
      surgical dressing demonstrated a slightly higher rate of infection (eight
      infections in 300 procedures, 2.67%) than non-use of a dressing (14 infections in
      753 procedures, 1.86%). Despite these trends, no statistically significant
      relationship was found between post-surgical infection and any of the treatment
      variables examined, including the use of perioperative antibiotics. CONCLUSIONS:
      The results of this study confirm previous research demonstrating a low rate of
      postoperative infection following periodontal surgical procedures. Although
      perioperative antibiotics are commonly used when performing certain regenerative
      and implant surgical procedures, data from this and other studies suggest that
      there may be no benefit in using antibiotics for the sole purpose of preventing
      post-surgical infections. Further large-scale, controlled clinical studies are
      warranted to determine the role of perioperative antibiotics in the prevention of
      periodontal post-surgical infections.

PMID- 15857065
TI  - Amine fluoride/stannous fluoride and chlorhexidine mouthwashes as adjuncts to
      single-stage dental implants: a comparative study.
AB  - BACKGROUND: The growing popularity of non-submerged dental implants in recent
      years requires a greater emphasis on microbial plaque control. Chlorhexidine
      (CHX), the most commonly used mouthwash in implant surgery, is sometimes
      associated with tooth staining and alteration in taste perception. Amine
      fluoride/stannous fluoride (AmF/SnF2) mouthwash has been shown to have anti
      infective properties; however, it has not been tested as an adjunct anti
      infective means in non-submerged dental implants. The purpose of this trial was
      to compare AmF/SnF2 and CHX mouthwashes as adjuncts to single-stage dental
      implants. METHODS: Thirty-three patients aged 34 to 79 (mean 54.30 +/- 8.69 SD)
      requiring dental implants were accepted into the study. Following comprehensive
      periodontal therapy patients received one to three non-submerged dental implants
      (maxilla: 17; mandible: 45; anterior: 3, posterior: 59). After surgery patients
      were given analgesics and antibiotics as well as 2,400 ml of coded mouthwash
      bottles previously randomized between the two above mentioned formulations.
      Clinical and radiographic parameters were recorded at baseline and 3 and 12
      months post-surgery. RESULTS: Twelve-month survival rates were 100% and 92.9% for
      the AmF/SnF2 and CHX groups, respectively. Compliance was slightly higher in the
      AmF/SnF2 group (84.35% +/- 3.39% versus 78.15% +/- 4.59% SE) but statistically
      similar. There was no statistically significant difference between the AmF/SnF2
      and CHX groups in staining index at 3 months (1.519 +/- 0.22 versus 1.457 +/-
      0.24 SE) and patient subjective evaluation of the mouthwashes. Radiographic bone
      loss was 0.79 +/- 0.23 and 1 +/- 0.13 SE at 3 months and 1.06 +/- 0.13 and 1.27
      +/- 0.25 at 12 months for the CHX and AmF/SnF2 groups, respectively; the
      difference was statistically insignificant (P = 0.388 and 0.504, respectively).
      CONCLUSION: Both CHX and AmF/SnF2 mouthwashes can be used post-surgically after
      one-stage implant surgery.

PMID- 15857066
TI  - Clinical performance of a regenerative strategy for intrabony defects: scientific
      evidence and clinical experience.
AB  - BACKGROUND: The aim of the present study was to evaluate the clinical performance
      of a regenerative strategy for the treatment of deep intrabony defects. METHODS:
      This patient cohort study involved 40 patients with one deep interdental
      intrabony defect each. They were treated with periodontal regeneration using four
      different regenerative methods (expanded polytetrafluoroethylene [ePTFE] titanium
      reinforced membranes, bioabsorbable membranes alone, bioabsorbable membranes with
      a bone replacement graft [combination], or enamel matrix derivative), according
      to predefined criteria and decision-making algorithms. Defects were accessed with
      papilla preservation flaps performed with the aid of an operating microscope and
      microsurgical instruments. A stringent plaque control regimen was enforced in all
      the patients during the 1-year observation period. Outcomes included evaluation
      of the complete primary closure of the interdental space (CLOSURE), gains in
      clinical attachment (CAL), and reductions in probing depths (PD). RESULTS:
      CLOSURE was achieved in all treated defects and was maintained in 90% of cases
      for the entire healing period. At 1 year the observed CAL gains were 6 +/- 1.8 mm
      on average, corresponding to a resolution of 92.1% +/- 12% of the initial
      intrabony (CAL%) component of the defect. Average PD reduction was 6.1 +/- 1.9 mm
      and was associated with minimal increase in gingival recession (-0.1 +/- 0.7 mm).
      The 12 sites treated with titanium reinforced ePTFE membranes resulted in a 1
      year CAL gain of 6.8 +/- 2.2 mm (CAL%: 94.7 +/- 13.4); the 11 cases treated with
      combination therapy showed a 1-year CAL gain of 5.4 +/- 1.7 mm (CAL%: 88.2 +/-
      9.6); the seven sites treated with bioabsorbable barriers resulted in 5.9 +/- 1.2
      mm of CAL gain (CAL%: 88.9 +/- 11.5); and the 10 sites treated with enamel matrix
      gained on average 5.9 +/- 1.5 mm of CAL (CAL%: 88.9 +/- 11.5). No significant
      differences were observed among the four approaches. CONCLUSION: The use of an
      evidence-based regenerative strategy resulted in clinically relevant amounts of
      CAL gains, shallow pockets, and minimal gingival recession with the four
      regenerative approaches.

PMID- 15857067
TI  - 2% sodium fluoride-iontophoresis compared to a commercially available
      desensitizing agent.
AB  - BACKGROUND: Dentin hypersensitivity is a common clinical condition and age-old
      complaint, presenting problems to both the patient and the dentist. Besides
      causing discomfort, the condition may deter a person from establishing or
      maintaining adequate oral hygiene procedures, further complicating oral health.
      The failure to practice satisfactory plaque control has well-established
      consequences on gingival and periodontal health. Thus, a cycle of sensitive teeth
      leading to reduced plaque control, more periodontal disease, and more recession
      may be established. METHODS: The hypersensitive teeth were identified by the
      patient and verified by the light stroke of a dental explorer along the cervical
      area of all teeth present. Subjects fulfilling the inclusion and exclusion
      criteria were evaluated using tactile, 1-second air blast, and cold water
      stimuli, and the subject's response was recorded on the verbal rating scale. A
      total of 425 teeth from 50 patients included in this study were randomly divided
      into two groups: group 1, who received 2% sodium fluoride-iontophoresis (NaF) and
      group 2, who received an aqueous solution of hydroxy-ethyl-methacrylate and
      glutaraldehyde (HEMA-G). The teeth were evaluated immediately after treatment and
      at 2 weeks, 1 month, and 3 months. In case of failure at the 2-week interval, the
      affected tooth was retreated with the same drug as before and evaluated further.
      RESULTS: The results were statistically analyzed, and it was found that group 1
      treatment was more effective than group 2 at 1- and 3-month intervals. There was
      a comparatively greater recurrence of hypersensitivity in group 2. A comparable
      number of teeth required repeat dosage in both groups. Teeth which required
      repeat dosage had greater mean discomfort scores at baseline for all three tests
      than the teeth which did not require a repeat dose. CONCLUSIONS: Both agents
      showed significant reduction in sensitivity at all time intervals compared to
      baseline; however, NaF had a comparatively greater effect than HEMA-G at both the
      1- and 3-month intervals; an almost equal number of teeth in both groups required
      repeat doses. Teeth with a higher initial sensitivity score required a repeat
      dose. Both agents were found to be equally effective immediately after
      application; the 2% NaF was comparatively better than HEMA-G in providing long
      term relief.

PMID- 15857068
TI  - Marginal periodontium as a potential reservoir of human papillomavirus in oral
      mucosa.
AB  - BACKGROUND: Although human papillomaviruses (HPVs) are associated with a number
      of proliferative epithelial lesions including squamous cell malignancies, they
      can also be detected in the normal oral mucosa in 10% to 20% of the adult
      population. However, the point of entry and the site of replication of HPV in the
      oral cavity are not known. Since the gingival pocket is the only site in the oral
      mucosa where basal cells, known to be targets of HPV at other mucosal sites, are
      normally exposed to the environment, we hypothesized that this could be the site
      of latent HPV. METHODS: Gingival biopsies taken from 38 individuals with
      clinically diagnosed periodontal disease were examined. The presence of HPV DNA
      was studied by using nested PCR (polymerase chain reaction with MY09/MY11 and
      GP05+/GP06+ primers targeting the L1 region of HPV), followed by subsequent
      hybridization with a cocktail of 12 high-risk HPV oligoprobes and in situ
      hybridization (ISH) with probes for HPV screening and the HPV subtype 16.
      RESULTS: In the present study, high-risk HPV types were detected in 26% (8/31) of
      the gingival biopsies with PCR. By using in situ hybridization, the viral DNA was
      localized to the coronal part of the junctional epithelium in the gingival
      pocket. CONCLUSIONS: The results suggest that the periodontal pocket might serve
      as a reservoir of HPVs in oral mucosa. While having important implications in
      understanding the HPV transmission, this observation does not rule out the
      possibility that HPV may be involved in the initiation of periodontal disease.

PMID- 15857069
TI  - Comparison of human mandibular osteoblasts grown on two commercially available
      titanium implant surfaces.
AB  - BACKGROUND: Surface characteristics play a major role in determining tissue
      response to implants and therefore their clinical outcome. The aim of the present
      study was to compare two commercially available titanium surfaces: plasma sprayed
      (TPS) and sand-blasted, acid-etched surface (SLA). METHODS: The surfaces were
      characterized by roughness testing, scanning electronic microscopy (SEM), Raman
      spectroscopy, and protein adsorption to determine their microtopographic and
      chemical properties. The effect of the surfaces on human mandibular osteoblasts
      was then studied in terms of cell morphology, adhesion, proliferation, and
      differentiation. Human osteoblasts from the mandible were cultured on these two
      surfaces and evaluated at 3, 6, 24, and 48 hours to determine cell attachment and
      morphology. Growth and differentiation kinetics were subsequently investigated by
      evaluating cell growth, alkaline phosphatase activity, osteocalcin and
      osteoprotegerin production at 7, 14, and 21 days. RESULTS: Although roughness was
      quite similar, the two surfaces presented strong differences in their topography,
      and cell morphology varied as a consequence. Osteoblasts on SLA appeared more
      elongated and spindle shaped than those on TPS, and their adhesion at 3 and 6
      hours was weaker, but reached that of cells on TPS at hour 24. Cell proliferation
      was greater on SLA surfaces but differentiation parameters; i.e., alkaline
      phosphatase and osteocalcin, provided better results on TPS surfaces.
      Osteoprotegerin production was enhanced on TPS surfaces at days 14 and 21.
      CONCLUSION: Although cells grown on both surfaces exhibited good adhesion
      capabilities, a well-differentiated osteoblastic phenotype, and maintained a
      clear proliferation potential, our study suggests that plasma-sprayed treatment
      offers a better performance than SLA by creating, at least in the early phases,
      better conditions for tissue healing.

PMID- 15857070
TI  - Inhibitory effects of areca nut extracts on phagocytosis of Actinobacillus
      actinomycetemcomitans ATCC 33384 by neutrophils.
AB  - BACKGROUND: Areca quid chewers have a higher prevalence of periodontal disease
      than non-chewers. Little is known about the influence of areca quid on the immune
      system. This study was to determine the possible effects of the areca nut on
      phagocytic activity of human neutrophils. METHODS: Aqueous extracts of ripe areca
      nut without husk (rANE), fresh and tender areca nut with husk (tANE), a major
      alkaloid (arecoline), and a phenolic component ([+]-catechin) of areca nut were
      examined for their effects on cellular viability using trypan blue exclusion
      assay. The possible effects on the phagocytic activity of neutrophils against a
      periodontal pathogen, Actinobacillus actinomycetemcomitans ATCC 33384, were
      determined using flow cytometry and confocal laser scanning microscopy. RESULTS:
      At the concentrations tested, rANE, tANE, arecoline, and (+)-catechin did not
      significantly affect viability of neutrophils. However, rANE, tANE, arecoline,
      and (+)-catechin inhibited the phagocytic activity of neutrophils in a dose
      dependent manner. Approximately 50% of the relative phagocytic activity of
      neutrophils was affected when 50 microg/ml of rANE, 400 microg/ml of tANE, 20,000
      microg/ml of arecoline, or 2,500 microg/ml of (+)- catechin was used. Decreased
      levels of internalized fluorescent bacteria were also demonstrated. However,
      arecoline or (+)-catechin alone could not be used to explain the inhibitory
      effects observed for rANE and tANE. CONCLUSIONS: Components of areca nut reduced
      the uptake of A. actinomycetemcomitans ATCC 33384 by human neutrophils. The
      inhibition of areca nut on phagocytosis of neutrophils may be one possible
      mechanism by which the areca nut compromises the periodontal health of areca quid
      chewers.

PMID- 15857071
TI  - Prospective assessment of the use of enamel matrix proteins with minimally
      invasive surgery.
AB  - BACKGROUND: Minimally invasive surgery (MIS) is a surgical technique using very
      small incisions, indicated for performing regenerative therapy in periodontal
      defects. Enamel matrix proteins (EMP) have been shown to enhance periodontal
      regeneration. This study was undertaken to determine the effect of using EMP in
      combination with an MIS approach. METHODS: Patients from two private periodontal
      practices with chronic periodontitis who, following non-surgical therapy, had one
      or more sites with probing depths (PD) of > or =6 mm were included in the study.
      An MIS approach was utilized for surgical access. Following surgical debridement,
      EMP was placed into the bony defect. The surgical sites were reevaluated after at
      least 11 months. RESULTS: Surgical treatment was performed at 160 sites in 16
      patients. No significant differences were noted in the results between the two
      offices and the data were combined. Mean PD reduction (P = 0.002) and attachment
      level improvements (P = 0.012) were significantly greater than 3 mm with mean
      post-surgical PD of 3.17 mm and attachment levels of 4.05 mm, based on subject
      means. Mean change in recession following surgery was negligible (0.01 mm). All
      sites were considered to be clinically successful. CONCLUSION: The combination of
      MIS and EMP yields significant reductions in probing depths and improvements in
      attachment levels while producing little or no increase in recession.

PMID- 15857072
TI  - Radiographic evaluation of dental implants placed using an osteotome technique.
AB  - BACKGROUND: The osteotome technique has been successfully used for implant
      placement when a limited vertical height is available at posterior maxilla.
      However, it is not clear if new bone is formed at the apical portion of the
      implant placed by this technique without any bone graft. The aim of this study
      was to radiographically evaluate bone formation around dental implant surfaces
      exposed to the space created at the sinus floor without the presence of any graft
      material. METHODS: Forty patients (21 male, 19 female; mean age 46.7 years) who
      received a total of 75 dental implants together with indirect sinus lifting
      procedure were included. Initial and 6-month postoperative panoramic films were
      scanned and analyzed using a commercially available software program. Implants
      were divided into two groups: initial alveolar bone height <9 mm or > or =9 mm.
      This helped determine the effect of available bone and exposed implant surface on
      bone formation in a system where the shortest implant was 8 mm. RESULTS: The mean
      implant length placed at locations with <9 mm initial bone height (mean 7 +/- 1.3
      mm, N = 29 implants) was 11 +/- 1.7 mm; gain in bone height was 3.9 +/- 1.9 mm.
      At locations where minimum bone height was 9 mm (mean 10.4 +/- 0.7 mm), 44
      implants were placed with a 13.5 +/- 1.06 mm mean length. Mean gain in bone
      height was 2.9 +/- 1.2 mm at these sites. Two implants were lost at stage 2
      surgery. The success rate after 25 months of loading was 97.3%. CONCLUSIONS: It
      is possible to radiographically observe a gain of approximately 3 to 4 mm of bone
      from the sinus floor to the implant apex. The amount of initial alveolar bone
      height, presence of sinus membrane perforation, and the amount of exposed implant
      surface appear to play a role in the presence or absence of radiopacity within
      the elevated sinus floor, following 6 months of healing.

PMID- 15857073
TI  - Implant stability measurements for implants placed at the time of extraction: a
      cohort, prospective clinical trial.
AB  - BACKGROUND: Studies indicate that implants placed at the time of extraction have
      high success rates. Implants must be stable at the time of insertion. Presently
      there are no data indicating the degree of implant stability when implants are
      placed at the time of extraction. This study evaluated changes in stability of
      implants from implant placement to abutment connection utilizing resonance
      frequency analysis (RFA). The unit of measurement was the international stability
      quotient (ISQ). METHODS: Prior to treatment, patients were given medical history
      and dental evaluations. Periapical and panogram radiographs were taken. Fifty-two
      patients requiring extraction of one or two teeth and implant placement
      immediately after extraction were enrolled in this study. Under conscious
      sedation and local anesthesia or local anesthesia alone, teeth were
      atraumatically removed and the extraction sockets were debrided. A total of 73
      dental implants (57 in the maxilla, 16 in the mandible) were placed. Using a one
      stage approach, all implants were placed within the patient's alveolar envelope
      and were never placed directly into extraction sockets. All implants were placed
      into contained extraction sites. Bone augmentation procedures were not performed.
      After implant insertion, the RFA electronic transducer was attached to the head
      of the implant with the retaining screw. The device was attached to a computer
      designed to register RFA scores in ISQ units. RFA measurements were taken at
      implant placement and abutment connection. Bone qualities, quantity, implant
      length and width as well as site of placement were recorded. RESULTS: The average
      interval between implant insertion and abutment connection was 5.6 months (SD
      2.05). Two implants were lost between implant insertion and 1 year. At 2 to 3
      years, the cumulative survival was 97.2%. Resonance frequency measurements at
      implant placement showed a mean primary stability of 62.0 (SE 1.1; range 43 to 83
      ISQ) and a mean secondary stability after 1 year of 64.0 (SE 1.2; range 40 to 98
      ISQ) for all implants. The increase was marginally significant (generalized
      estimating equation z-statistic = 1.79; P value = 0.07). CONCLUSIONS: Implants
      placed at the time of extraction and inserted into native bone and not directly
      into extractions sockets have a high degree of initial stability as evidenced by
      RFA measurements. Implants with initial high ISQ levels revealed a slight drop in
      levels over time, while implants with levels lower than 60 had increases in
      levels between implant insertion and abutment connection. At 2 to 3 years the
      cumulative survival rate was 97.2%.

PMID- 15857074
TI  - Relative contribution of patient-, tooth-, and site-associated variability on the
      clinical outcomes of subgingival debridement. I. Probing depths.
AB  - BACKGROUND: The objective of this clinical trial was to assess the relative
      contribution of patient-, tooth-, and site-associated variables on changes in
      probing depths (PD) following delivery of a standard non-surgical phase of
      periodontal therapy. METHODS: Ninety-four (94) systemically healthy subjects with
      severe generalized periodontitis were included in this 6-month prospective
      longitudinal study. Medical, periodontal, and microbiological parameters were
      collected at baseline and 2 and 6 months after completion of oral hygiene
      instructions, motivation, and subgingival debridement using a piezoelectric
      instrument. The relative contribution of patient-, tooth-, and site-associated
      variables was evaluated with a hierarchical multilevel analysis. RESULTS: Eighty
      percent (80%) of variability in PD reductions was attributed to site level
      parameters, while 12% was at the tooth level and 8% at the patient level. The
      multilevel analysis associated PD reductions with patient factors (cigarette
      smoking status and carriage of the rare allele of a specific polymorphism for the
      interleukin-6 [IL-6] gene), tooth factors (tooth mobility and tooth type), and
      site factors (mesial and distal location). Cigarette smoking and carriage of the
      rare allele of the IL- 6-174 G/C polymorphism were associated with less PD
      reduction. Incisors and canines responded better than premolars and molars. A
      dose-dependent effect of mobility was observed: teeth with higher baseline
      mobility resulted in significantly greater decreases in PD. At the site level,
      greater reductions were observed at interdental sites (compared to facial or
      oral), and at deeper sites (1.2 mm for 4 to 5 mm pockets and 2.4 mm for pockets >
      or =6 mm). CONCLUSION: These data provided an estimation of the relative
      contribution of site-, tooth-, and patient-associated variables in terms of PD
      reductions following a standard course of machine-driven subgingival debridement.

PMID- 15857075
TI  - Is periodontitis associated with oral neoplasms?
AB  - BACKGROUND: Infections have been suggested in the etiology of oral cancer. This
      study was carried out to evaluate the effect of periodontal disease on oral soft
      tissue lesions. METHODS: A total of 13,798 subjects aged 20 years and older with
      at least six natural teeth and who participated in the Third National Health and
      Nutrition Examination Survey (NHANES III) constituted the study population.
      Severity of periodontal disease was represented by clinical attachment loss (CAL)
      and was dichotomized as < or =1.5 mm versus >1.5 mm according to its
      distributions in the NHANES III population. Three separate dependent variables
      were employed: 1) tumor (non-specific); 2) precancerous lesions; and 3) any oral
      soft tissue lesion. The independent effect of CAL on those three dependent
      variables was assessed by weighted multiple logistic regression analyses
      adjusting for the effects of number of filled teeth, number of decayed teeth,
      presence of prosthesis, age, gender, race/ethnicity, education, tobacco, alcohol,
      occupational hazard, and interaction term "tobacco*occupational hazard." Odds
      ratios (OR) and their 95% confidence intervals (CI) were calculated. RESULTS: CAL
      was not related to the presence of any soft tissue lesion (OR = 1.09, 95% CI:
      0.91 to 1.31), but was specifically related to the presence of tumor (OR = 4.57,
      95% CI: 2.25 to 9.30) and precancerous lesions (OR = 1.55, 95% CI: 1.06 to 2.27).
      CONCLUSION: This study suggests associations between periodontal disease and the
      risk for precancerous lesions and tumors generating a hypothesis about a possible
      relationship between periodontal disease and oral neoplasms. Prospective or well
      designed case-control studies with histologically confirmed incident oral cancer
      cases are necessary to confirm this relationship.

PMID- 15857076
TI  - Lactate dehydrogenase activity in human gingival crevicular fluid during
      orthodontic treatment: a controlled, short-term longitudinal study.
AB  - BACKGROUND: During orthodontic tooth movement, the early response of periodontal
      tissues to mechanical stress is an acute inflammatory one. This study uses a
      longitudinal design to examine lactate dehydrogenase (LDH) activity in gingival
      crevicular fluid (GCF) to determine if GCF LDH can be used as a diagnostic aid in
      monitoring tooth movement and tissue response during orthodontic treatment.
      METHODS: Seventeen patients (mean age: 16.1 years) participated in the study.
      Each patient was undergoing treatment for distal movement, and an upper first
      molar served as the test tooth (TT), while the contralateral (CT) and antagonist
      (AT) teeth were used as controls. The CT was included in the orthodontic
      appliance, but was not subjected to the distal movement; the AT was free from any
      orthodontic appliance. The GCF around the experimental teeth was harvested from
      both mesial and distal tooth sites immediately before appliance activation, and
      on days 7, 14, and 21. Clinical gingival conditions were also recorded. RESULTS:
      Gingival crevicular fluid LDH activity was significantly elevated in all sites of
      the TT and CT, as compared to the AT, where LDH activity remained at the baseline
      level throughout the study. Enzyme activity levels were also greater in the TT
      than in the CT, and in the compression sites. CONCLUSIONS: Our results suggest
      that GCF LDH levels reflect the biological activity that takes place in the
      periodontium during orthodontic movement, and therefore they can be used as a
      diagnostic tool for monitoring for correct orthodontic tooth movement in clinical
      practice.

PMID- 15857077
TI  - Diabetes and periodontal disease: a case-control study.
AB  - BACKGROUND: Periodontitis is often associated with diabetes and might be
      considered one of the chronic complications of diabetes mellitus, both in Type 1
      (T1DM) and Type 2 (T2DM). This case-control study was designed to evaluate the
      possible association between non-insulin-dependent diabetes (T2DM) and clinical
      and microbiological periodontal disease among adult Sardinians. METHODS: A total
      of 212 individuals participated in this study: 71 T2DM patients aged 61.0 +/-
      11.0 years and 141 non-diabetic controls in good general health aged 59.1 +/- 9.2
      years. All subjects were given a clinical periodontal examination for probing
      depth, attachment level, presence of calculus, bleeding on probing, and
      assessment of plaque. Subgingival plaque samples were obtained, and P.
      gingivalis, P. intermedia, and T. forsythensis were identified using multiplex
      polymerase chain reaction. RESULTS: T2DM patients showed a significantly lower
      number of teeth present (P = 0.002); a significant increase in number of probing
      depths >4 mm, and percent of pocket depths >4 mm (P = 0.04 and P = 0.05,
      respectively); periodontitis (P = 0.046); bleeding on probing (P = 0.02); and
      plaque index (P = 0.01). A significant association with diabetes was detected for
      plaque (X2= 4.46; P <0.05) and bleeding on probing (X2= 3.60; P <0.05).
      Concerning bacteria prevalence, a positive association was detected for P.
      gingivalis (X2= 2.80; P <0.05) and T. forsythensis (X2= 3.87; P <0.05). Presence
      of plaque was positively associated with case status (odds ratio [OR] = 1.3; 95%
      confidence interval [CI]: 1.2, 3.6) and with prevalence of P. gingivalis and T.
      forsythensis (OR = 1.2, 95% CI: 1.3, 2.2; and 1.2, 95% CI: 1.2, 1.8,
      respectively). CONCLUSION: Patients with T2DM undoubtedly have a susceptibility
      for more severe periodontal disease.

PMID- 15857078
TI  - Clinical response of azithromycin as an adjunct to non-surgical periodontal
      therapy in smokers.
AB  - BACKGROUND: Antibiotic therapy can be used in very specific periodontal treatment
      situations such as in refractory cases of periodontal disease found to be more
      prevalent in smokers. This study was designed to determine the efficacy of
      azithromycin (AZM) when combined with scaling and root planing (SRP) for the
      treatment of moderate to severe chronic periodontitis in smokers. METHODS: Thirty
      one subjects were enrolled into a 6-month randomized, single-masked trial to
      evaluate clinical, microbial (using benzoyl- DL-arginine naphthylamine [BANA]
      assay), and gingival crevicular fluid (GCF) pyridinoline cross-linked
      carboxyterminal telopeptide of type I collagen (ICTP) levels in response to SRP
      alone or SRP + AZM. At baseline, patients who smoked > or =1 pack per day of
      cigarettes who presented with at least five sites with probing depths (PD) of >
      or =5 mm with bleeding on probing (BOP) were randomized into the test or control
      groups. At baseline and 3 and 6 months, clinical measurements (probing depth
      [PD], clinical attachment loss [CAL], and bleeding on probing [BOP]) were
      performed. GCF bone marker assessment (Ctelopeptide [ICTP] as well as BANA test
      analyses) were performed at baseline, 14 days, and 3 and 6 months. RESULTS: The
      results demonstrated that both groups displayed clinical improvements in PD and
      CAL that were sustained for 6 months. Using a subject-based analysis, patients
      treated with SRP + AZM showed enhanced reductions in PD and gains in CAL at
      moderate (4 to 6 mm) and deep sites (>6 mm) (P <0.05). Furthermore, SRP + AZM
      resulted in greater reductions in BANA levels compared to SRP alone (P <0.05)
      while rebounds in BANA levels were noted in control group at the 6-month
      evaluation. No statistically significant differences between groups on mean BOP
      and ICTP levels during the course of the study were noted. CONCLUSIONS: The
      utilization of AZM in combination with SRP improves the efficacy of non-surgical
      periodontal therapy in reducing probing depth and improving attachment levels in
      smokers with moderate to advanced attachment loss.

PMID- 15857079
TI  - Calprotectin expression in human monocytes: induction by porphyromonas gingivalis
      lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-1beta.
AB  - BACKGROUND: Calprotectin is a major cytosolic protein of monocytes and
      granulocytes. It is increased in inflammatory tissues and is detected at high
      levels in the gingival crevicular fluid (GCF) of periodontitis patients. We
      previously reported that lipopolysaccharide of Porphyromonas gingivalis (P-LPS)
      and cytokines induced the release of calprotectin from monocytes isolated from
      human peripheral blood. The mechanisms of calprotectin expression and presence of
      its regulation factors in periodontal disease are unknown. On the other hand, P
      LPS and cytokines are significant etiologic factors in the initiation and
      progression of periodontal diseases. In this study, we investigated the
      expression and production of calprotectin from human monocytes by examining the
      effects of lipopolysaccharide of P-LPS, tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-1beta (IL-1beta). METHODS: Monocytes were isolated from the
      peripheral blood of healthy donors and cultured in the presence or absence of P
      LPS, TNF-alpha, or IL-1beta. The expressions of calprotectin mRNAs (MRP8 and
      MRP14) were detected by Northern blotting. The contents of calprotectin in the
      cells and medium fractions were determined by enzyme-linked immunosorbent assay
      (ELISA). The DNA binding activity of C/EBPalpha, a transcription factor of MRP14,
      was assessed by electrophoretic mobility shift DNA-binding assay (EMSA). RESULTS:
      P-LPS, TNF-alpha, and IL-1beta induced MRP8/14 mRNAs and calprotectin production
      in monocytes. These factors also induced DNA CEBPalpha binding activity in
      monocytes. P-LPS increased MRP14 mRNA expression in monocytes to the maximum
      level, about two times the control level after 24 hours treatment, but did not
      enhance the basal level of MRP8. When the effects of TNF-alpha and IL-1beta on
      those mRNAs were investigated, both MRP8 and MRP14 significantly increased to
      about 2- and 2.5-fold the control level, respectively. Increases of MRP8/14 mRNA
      expression were followed by their protein production at about 2-fold the basal
      amount. DNA binding activity of C/EBPalpha was increased in P-LPS, TNF-alpha, and
      IL-1beta-treated monocytes. CONCLUSIONS: These results demonstrate that P-LPS,
      TNF-alpha, and IL-1beta induce calprotectin production from human monocytes and
      that this production is associated with the activation of DNA C/EBPalpha binding
      complex.

PMID- 15857080
TI  - Depletion of polyamines and increase of transforming growth factor-beta1, c-myc,
      collagen-type I, matrix metalloproteinase-1, and metalloproteinase-2 mRNA in
      primary human gingival fibroblasts.
AB  - BACKGROUND: The polyamines spermidine, spermine, and putrescine are known to be
      deeply linked with growth processes, gene expression, and extracellular matrix
      synthesis. Their cellular content depends primarily on the activity of the enzyme
      ornithine decarboxylase. High levels of ornithine decarboxylase and polyamines
      have been found in proliferative, inflammatory, and neoplastic pathologies of the
      oral cavity and in gingival fluid. Difluoromethylornithine (DFMO) selectively
      inhibits ornithine decarboxylase, thus depleting polyamine content and preventing
      cell proliferation and synthesis activity. The aim of this study was to
      investigate whether DFMO treatment could modify the genes involved in cell
      proliferation and extracellular matrix turnover. METHODS: Fibroblasts derived
      from non-inflamed gingiva were maintained in Dulbecco's modified Eagle's medium
      (DMEM) plus alpha-difluoromethylornithine for 4 days. At 0, 24, 48, 72, and 96
      hours cell number was assessed, polyamine levels were quantified with high
      performance liquid chromatography (HPLC) method, and transforming growth factor
      beta1 (TGF-beta1), c-myc, matrix metalloproteinases (MMP)-1 and 2, collagen type
      I (COL-I) and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were
      evaluated by reverse transcription polymerase chain reaction (RT-PCR). RESULTS:
      Fibroblasts treated with DFMO significantly decreased cell proliferation,
      ornithine decarboxylase activity, and putrescine levels at all treatment times,
      spermidine after 72 and 96 hours, and spermine after 96 hours of culture. Total
      polyamines decreased (P < or =0.01) at 96 hours after DFMO treatment, while c
      myc, TGF-beta1, MMP-1 and 2, COL-I mRNA significantly increased. Conversely, TIMP
      1 did not show any significant change. The polyamines trend was not correlated to
      c-myc, TGF-beta1, MMP-1 and -2, and TIMP-1 mRNA levels. Transforming growth
      factor-beta1 and c-myc mRNA expression were related and correlated to MMP-1 and
      2, COL-I and TIMP-1 mRNA trend after DFMO treatment. CONCLUSIONS: Our data show
      that as the polyamine content decreases, TGF-beta1, c-myc, MMP-1 and -2, and COL
      I mRNA levels increase, therefore a negative regulatory role of the polyamines on
      the mRNA expression could be suggested.

PMID- 15857081
TI  - The use of guided tissue regeneration principles in endodontic surgery for
      induced chronic periodontic-endodontic lesions: a clinical, radiographic, and
      histologic evaluation.
AB  - BACKGROUND: Chronic periodontic-endodontic lesions are not uncommon in clinical
      practice and their regenerative capacity has long been questioned. However, there
      are no published studies investigating the application of guided tissue
      regeneration techniques in combination with endodontic surgery using an induced
      perio-endo defect model. This study evaluated the clinical, radiographic, and
      histologic outcomes of three surgical procedures used to treat induced perio-endo
      lesions. METHODS: Pulpal necrosis was induced in foxhounds along with surgical
      removal of radicular buccal bone. After 4 weeks, chronic lesions were clinically
      and radiographically assessed. Treatment surgery consisted of apicoectomy, root
      canal instrumentation, and retrofilling with mineral trioxide aggregate. Teeth
      were then assigned to one of the following treatment groups: open flap
      debridement only (OFD), OFD with bioabsorbable porcine-derived collagen membrane
      (BG), or OFD with BG and anorganic bovine bone matrix (BO/BG). Clinical
      parameters and standardized radiographs were assessed at defect creation;
      treatment surgery; and at 1, 2, 4, and 6 months. Animals were sacrificed at 6
      months and specimens prepared for histometric analysis. RESULTS: Clinical and
      radiographic conditions improved during the study period. Mean epithelial
      attachment was similar between all groups. Mean connective tissue attachment for
      groups OFD, BG, and BO/BG was 3.79 mm, 2.63 mm, and 1.75 mm, respectively, and
      mean radicular bone height was 2.16 mm, 3.24 mm, and 3.45 mm, respectively.
      Statistically significant increases in the amount of new cementum were observed
      in groups BG and BO/BG when compared with OFD (P <0.05). CONCLUSIONS: Treatment
      of combined induced perio-endo lesions using bioabsorbable collagen membranes
      alone or in combination with anorganic bovine bone matrix resulted in increased
      amounts of bone, periodontal ligament, and significant increases in the amount of
      new cementum when compared to open flap debridement in a canine model.

PMID- 15857082
TI  - Prevalence of maxillary sinus disease and abnormalities in patients scheduled for
      sinus lift procedures.
AB  - BACKGROUND: The purpose of the present study was to determine the prevalence of
      sinus disease and abnormalities among patients scheduled to undergo direct sinus
      augmentation. METHODS: Forty-five patients attending a private periodontal
      practice and consecutively treatment planned for sinus augmentation were referred
      for otorhinolaryngologic evaluation, which included a medical history and
      radiographic (computed tomography), clinical, and endoscopic examinations.
      Pathological findings were recorded and otorhinolaryngologic treatment was
      provided. Six months later the sinus augmentation procedure was performed and
      followed by postoperative evaluations for 4 to 6 months. RESULTS: Of the 45
      subjects, 98% (44) were diagnosed with chronic periodontitis, 51% were smokers,
      and 27% reported a history of symptoms indicative of sinus disease. Eighteen
      subjects were diagnosed with sinus disease and/or abnormalities. The diagnosed
      conditions included chronic sinusitis, sinus cysts, nasal septum deviation, and
      ostium stenosis. No significant differences in age, gender, or smoking status
      between patients with and without sinus conditions were found (P >0.05). There
      was a significant association between history of symptoms and diagnosis of sinus
      conditions (P <0.0001). Three subjects (one treated for preoperative sinus
      conditions) experienced notable intra- or postoperative complications related to
      the sinus augmentation procedure. CONCLUSIONS: The results indicate that, in a
      population of patients with chronic periodontitis, presence of sinus conditions
      is strongly associated with a history of indicative symptoms and is independent
      of age, gender, and smoking status. The results reinforce the importance of
      careful detailed history taking and thorough clinical and radiographic evaluation
      prior to performing sinus augmentation.

PMID- 15857083
TI  - Aggressive periodontitis in an urban population in southern Brazil.
AB  - BACKGROUND: There are limited data about the epidemiology and risk factors for
      aggressive periodontitis (AgP) in Latin American and Brazilian populations. The
      aim of this study was to assess the prevalence of AgP and the risk associated
      with demographic variables, smoking behavior, and other periodontal variables in
      a young urban population in southern Brazil. METHODS: A representative sample of
      612 subjects aged 14 to 29 years were sampled using a multistage probability
      method. A full-mouth clinical examination of six sites per tooth and an interview
      were performed in a mobile examination center. Subjects in the age groups 14 to
      19 years and 20 to 29 years were classified with AgP if they had four or more
      teeth with attachment loss > or =4 mm or > or =5 mm, respectively. RESULTS: AgP
      was found in 5.5% of the subjects. The disease occurred equally among males and
      females, but was twice as prevalent among non-whites than whites. In the age
      groups 20 to 24 years and 25 to 29 years, the AgP subjects had a significantly
      higher prevalence of tooth loss (90.2% versus 40.4% and 86.1% versus 43.4%, P
      <0.01) and mean number of missing teeth (2.6 versus 0.9 and 3.4 versus 1.5, P
      <0.05) than subjects without attachment loss. The AgP subjects also had
      significantly higher percentages of sites with dental plaque (P <0.0001),
      gingival bleeding (P <0.05), and supragingival calculus (P <0.0001) than normal
      subjects. The risk for AgP was higher in the 25- to 29-year than the 14- to 19
      year age groups (odds ratio [OR] = 6.2), in the low than middle or high
      socioeconomic status (OR = 4.5), in moderate or heavy smokers than nonsmokers (OR
      = 3.1), and in subjects with > or =10% versus <10% sites with supragingival
      calculus (OR = 3.6). CONCLUSION: Socioeconomic status, smoking, and dental
      calculus were significant risk indicators of aggressive periodontitis in this
      population. Suitable periodontal prevention programs implementing these risk
      indicators may prevent or reduce the prevalence of aggressive periodontitis in
      this and similar populations.

PMID- 15857084
TI  - Histologic evaluation of three methods of periodontal root surface treatment in
      humans.
AB  - BACKGROUND: Removing subgingival plaque and calculus is a major goal of
      periodontal treatment. Few attempts have been made to evaluate the use of lasers
      for root surface debridement in periodontal therapy. The aim of the present study
      was to compare, histologically, the effects of hand instrumentation, ultrasonic
      instrumentation, and CO2 lasers on the root surfaces of teeth treated in situ.
      METHODS: A total of 33 teeth scheduled for extraction due to severe periodontal
      disease were divided into three groups. In the first group, teeth were treated by
      ultrasonic bactericidal curettage (UBC) with an ultrasonic scaler; in the second
      group, teeth were treated by hand instrumentation; and in the third group, after
      hand instrumentation, roots were lased by a CO2 laser. The samples were then
      processed for histological examination. RESULTS: In the first and second groups,
      plaque and calculus were present in interradicular septa, lacunae, and surface
      concavities. In the third group, surfaces of specimens treated by a low-power
      defocused CO2 laser showed areas devoid of cementum, with completely sealed
      dentinal tubules, and no bacterial cell remnants. CONCLUSIONS: The CO2 laser
      treatment, used at low power and in the defocused mode, combined with traditional
      mechanical instrumentation, could improve root surface debridement of
      periodontally involved teeth. More extensive, long-term studies are needed to
      confirm this hypothesis.

PMID- 15857085
TI  - An 8-year retrospective study: 1,100 patients receiving 1,557 implants using the
      minimally invasive hydraulic sinus condensing technique.
AB  - BACKGROUND: For many clinicians, inadequate alveolar bone height and anatomical
      features of the maxillary sinus complicate sinus lift procedures and placement of
      endosseous implants. We present a new internal crestal approach that addresses
      these issues. METHODS: Sinus burs and condensers of increasing width are used in
      conjunction with pliable atraumatic bone grafting mixture and hydraulic pressure
      from a surgical handpiece. The risk of a membrane perforation is minimized when
      the surgeon's tactile skill is administered in a two-stage process to first
      loosen and then graft bone particulate under the Schneiderian membrane. Threaded
      implants can then be placed in the same visit and secured via primary closure.
      RESULTS: A retrospective investigation of 1,100 cases showed that eight implants
      failed and 14 required longer healing periods in patients with alveolar ridge
      heights varying between <1 to 5 mm. CONCLUSIONS: Our experience suggests that
      hydraulic sinus condensing is a predictable and minimally invasive alternative
      for prosthetic rehabilitation of maxillary anterior and posterior regions in the
      presence of anatomical restrictions to implant placement.

PMID- 15857086
TI  - A novel mutation of the cathepsin C gene in a thai family with Papillon-Lefevre
      syndrome.
AB  - BACKGROUND: Papillon-Lefevre syndrome (PLS) is a rare autosomal recessive
      disorder characterized by palmar- plantar hyperkeratosis and rapid periodontal
      destruction of both primary and permanent dentitions. It has been shown that the
      disease is caused by cathepsin C gene (CTSC) mutation leading to the deficiency
      of cathepsin C enzymatic activity. This study demonstrates the clinical
      manifestations and CTSC mutational and enzymatic activity analyses in a 5-year
      old Thai male PLS patient and his parents. METHODS: Peripheral blood samples were
      obtained for genomic DNA isolation. All exons of the CTSC gene were amplified by
      polymerase chain reaction (PCR) using specific primers. Mutations were identified
      by DNA sequencing. Verification of the mutation was performed by digestion of PCR
      products by restriction endonucleases. The cathepsin C enzymatic activity was
      determined using the synthetic substrate glycyl- L-arginine-7-amino-4
      methylcoumarin. RESULTS: The patient demonstrated classical characteristics of
      PLS, including hyperkeratotic skin lesions. By the age of 5, all of his primary
      teeth were extracted due to severe periodontal infection. The parents had no
      physical abnormalities. The periodontal examination revealed localized mild
      periodontal destruction. Sequence analysis showed a nucleotide change at position
      90 from C >A (c.90C >A) which resulted in a change from cysteine residue to a
      premature stop codon at the amino acid position 30 in the exon 1. The HpyCH4V
      digestion revealed that the patient was homozygous, whereas both the father and
      mother were heterozygous carriers of this mutation. The cathepsin C activity was
      reduced in the patient's mother, and the activity in the patient was almost
      completely lost. CONCLUSIONS: This is the first study to demonstrate a CTSC gene
      mutation in a Thai family with PLS. The identified mutation is novel and
      potentially leads to the drastic reduction of the cathepsin C enzymatic activity.
      This suggests that the mutation is pathogenetic, causing the PLS. Mutational
      analysis in more members of the family is warranted to identify whether the
      mutation is inherited from a common ancestor.

PMID- 15857087
TI  - Evaluation of the inhibitory effect of triphala on PMN-type matrix
      metalloproteinase (MMP-9).
AB  - BACKGROUND: This study evaluated the inhibitory activity of triphala on PMN-type
      matrix metalloproteinase (MMP-9) expressed in adult periodontitis patients and
      compared its activity with another ayurvedic drug, kamillosan, and doxycycline,
      which has known inhibitory activity. METHODS: Matrix metalloproteinases (MMPs)
      were extracted from gingival tissue samples from 10 patients (six males, four
      females) with chronic periodontitis. Tissue extracts were treated with the drug
      solutions, the inhibition was analyzed by gelatin zymography, and the percentage
      of inhibition was determined by a gel documentation system. RESULTS: The activity
      of MMPs was significantly decreased with the use of the drugs. Triphala showed a
      76.6% reduction of MMP-9 activity, whereas kamillosan showed a 46.36% reduction
      at a concentration of 1,500 microg/ml (crude extract) and doxycycline showed a
      58.7% reduction at a concentration of 300 microg/ml (pure drug). CONCLUSION: The
      present study showed the strong inhibitory activity of triphala on PMN-type MMPs
      involved in the extracellular matrix (ECM) degradation during periodontitis.

PMID- 15857088
TI  - Clinical application of stereolithographic surgical guides for implant placement:
      preliminary results.
AB  - BACKGROUND: The success of implant-supported restorations requires detailed
      treatment planning, which includes the construction of a surgical guide.
      Recently, computer-aided rapid prototyping has been developed to construct
      surgical guides in an attempt to improve the precision of implant placement. The
      aim of the present study was to evaluate the match between the positions and axes
      of the planned and placed implants when a stereolithographic surgical guide is
      employed. METHODS: Six surgical guides used in four patients (three women, one
      man; age from 23 to 65 years old) were included in the study and 21 implants were
      placed. A radiographic template was fabricated and computer-assisted tomography
      (CT) was performed. The virtual implants were placed in the resulting 3
      dimensional image. Using a stereolithographic machine, liquid polymer was
      injected and laser-cured according to the CT image data with the planned
      implants, generating three surgical guides, with increasing tube diameters
      corresponding to each twist drill diameter (2.2, 3.2, and 4.0 mm), for each
      surgical area. During the implant operation, the surgical guide was placed on the
      jawbone and/or the teeth. After surgery, a new CT scan was taken. Software was
      used to fuse the images of planned and placed implants, and the locations and
      axes were compared. RESULTS: On average, the match between the planned and the
      placed implant axes was within 7.25 degrees +/- 2.67 degrees ; the differences in
      distance between the planned and placed positions at the implant shoulder were
      1.45 +/- 1.42 mm, and 2.99 +/- 1.77 mm at the implant apex. In all patients, a
      greater distance was found between the planned and placed positions at the
      implant apex than at the implant head. CONCLUSIONS: Clinical data suggest that
      computer-aided rapid prototyping of surgical guides may be useful in implant
      placement. However, the technique requires improvement to provide better
      stability of the guide during the surgery, in cases of unilateral bone-supported
      and non-tooth-supported guides. Further clinical studies, using greater number of
      patients, are necessary to evaluate the real impact of the stereolithographic
      surgical guide on implant therapy.

PMID- 15857089
TI  - New rapid polymerase chain reaction-immunochromatographic assay for Porphyromonas
      gingivalis.
AB  - BACKGROUND: A simple and rapid method for Porphyromonas gingivalis detection in
      clinical samples has been developed using polymerase chain reaction (PCR) and an
      immunochromatographic assay (ICA) with a lateral-flow device (strip) to detect
      species-specific 16S rRNA genes. METHODS: The PCR used a pair of primer sets
      labeled with fluorescein isothiocyanate (FITC) or biotin at each 5' terminus. The
      strip used a nitrocellulose membrane containing streptavidin conjugated to gold
      particles and anti-FITC line. RESULTS: PCR and ICA detected as few as 1 and 10
      cells of P. gingivalis, respectively. ICA required 5 to 10 minutes more than the
      initial PCR. The amplifications were not observed in other oral black-pigmented
      bacteria at concentrations of 10(6) colony forming unit (CFU). The ICA strips
      showed bands at more than 10(4) CFU/ml equivalents in clinical samples from
      periodontitis. CONCLUSIONS: A diagnostic assay based on PCR-ICA was developed for
      the detection of P. gingivalis, and results were obtained visually in 3 hours.
      PCR-ICA will be a valuable tool for the rapid detection of target bacteria by
      chair side.

PMID- 15857090
TI  - Serum, saliva, and gingival crevicular fluid osteocalcin: their relation to
      periodontal status and bone mineral density in postmenopausal women.
AB  - BACKGROUND: Periodontitis and osteoporosis are characterized by the loss of bone
      mass. Osteocalcin levels have been postulated as a marker of inhibition of bone
      formation. The aim of the present study was to assess plasma, saliva, and
      gingival crevicular fluid (GCF) levels of osteocalcin and correlate them with
      periodontitis and osteoporosis. METHODS: Seventy-three postmenopausal women, over
      35 years old, were recruited for the study. Serum, saliva, and GCF osteocalcin
      were measured. Vertebral bone mineral density was measured by dual-energy x-ray
      absorptiometry. Differences between groups were assessed by analysis of variance
      (ANOVA), chi-square test, and non-parametric Kruskal-Wallis test. RESULTS: Thirty
      four (46.6%) were classified in the normal healthy bone group, 11 women (15.1%)
      in the osteopenic group, and 28 women (38.4%) in the osteoporotic group. No
      statistically significant differences between these densitometric groups were
      observed in probing depth (P = 0.24); clinical attachment level (P = 0.11); or
      mean osteocalcin concentrations in serum, saliva, and GCF. Twenty-seven (37.0%)
      of the women were classified without periodontitis (NPG) and 63.0% (N = 46) with
      periodontal disease (PG). There were no statistical differences in serum and
      saliva osteocalcin concentrations between these two groups. GCF osteocalcin
      concentrations were significantly higher in the PG women than in the NPG group (P
      = 0.008). Mean probing depth correlated significantly with GCF osteocalcin
      concentrations (r = 0.35; P = 0.002). CONCLUSION: The results further support the
      concept that osteocalcin levels in GCF correlates with periodontal but not with
      osteoporosis status.

PMID- 15857091
TI  - Smoking cessation may present a positive impact on mandibular bone quality and
      periodontitis-related bone loss: a study in rats.
AB  - BACKGROUND: It has been previously shown that cigarette smoke inhalation (CSI)
      enhances bone loss in ligature-induced periodontitis. In this study, the
      hypothesis that the interruption of smoke exposure would reverse the impact of
      CSI on mandibular bone quality and periodontitis-related bone loss was tested.
      METHODS: Fifty-three Wistar rats were randomly assigned to one of the following
      groups: group 1: control, N = 16; group 2: 83 days of CSI prior to ligature
      placement, N = 17; or group 3: 90 days of CSI before and 60 days after ligature
      placement, N = 20. Animals were sacrificed 60 days after ligature placement, the
      jaws removed and immediately radiographed for photodensitometry analysis. Bone
      loss was histometrically evaluated. RESULTS: CSI did not affect unligated sites
      in either condition (P >0.05); however, smoke inhalation during the whole
      experimental period significantly enhanced bone loss in ligated teeth (P < 0.05).
      Moreover, similar levels of bone loss were observed for ligated teeth between the
      control and cessation groups (0.90 +/- 0.33 mm(2); 0.96 +/- 0.32 mm(2); 1.64 +/-
      0.65 mm(2); groups 1, 2 and 3, respectively). Radiographically, continuous
      exposure to cigarette smoke promoted a significantly reduced bone density (1.74
      +/- 0.38 aluminum equivalence [Al eq]; 1.74 +/- 0.14 Al eq; and 0.68 +/- 0.10 Al
      eq for groups 1, 2, and 3, respectively). CONCLUSIONS: Within the limits of the
      present investigation, it can be assumed that CSI may enhance bone loss in
      ligature-induced periodontitis, and negatively impact mandibular bone quality.
      Additionally, smoke exposure cessation seems to reverse its impact on mandibular
      bone, and, therefore, may be of clinical relevance.

PMID- 15857092
TI  - Changes in soluble adhesion molecules in gingival crevicular fluid following
      periodontal surgery.
AB  - BACKGROUND: Inflammation of periodontal tissues during postoperative wound
      healing is mediated by cell surface adhesion molecules. Soluble forms of these
      antigens have also been identified and shown to be important in immunoregulatory
      processes, but have previously not been investigated during periodontal repair
      and regeneration. The present study has examined the presence and possible
      changes in soluble intercellular adhesion molecule-1 (sICAM-1; CD54) and
      lymphocyte function-associated antigen-3 (sLFA-3; CD58) in gingival crevical
      fluid (GCF) following periodontal surgery. METHODS: GCF samples were collected
      from four groups: 1) a guided tissue regeneration (GTR) test; 2) a GTR control,
      at least one complete tooth unit away from the periodontal defect; 3) a
      conventional flap (CF) surgery; and 4) a crown lengthening (CL). Sandwich enzyme
      linked immunosorbent assay (ELISA) was used to measure the levels of sICAM-1 and
      sLFA-3 in the GCF samples. RESULTS: A marked increase in GCF volumes was found in
      all sites after surgery, although a persistent increase was associated only with
      the period of membrane retention at the GTR test sites. In addition, sICAM-1 and
      sLFA-3 were found in the GCF of healthy as well as diseased sites prior to
      treatment and the total amounts of both increased transiently following surgical
      intervention, especially sLFA-3. However, the concentrations of these GCF
      components, particularly sICAM-1, tended to decrease. CONCLUSIONS: The temporal
      decrease in the concentration of sICAM-1 and sLFA-3 in GCF may serve to enhance
      inflammatory reactions at surgically-treated periodontal sites, thereby limiting
      repair and regeneration in the periodontium. These soluble adhesion molecules may
      thereby be of potential therapeutic value and might also be useful markers for
      monitoring periodontal wound healing.

PMID- 15857093
TI  - Implants in patients treated for generalized aggressive and chronic
      periodontitis: a 3-year prospective longitudinal study.
AB  - BACKGROUND: The aim of the present prospective longitudinal study of
      periodontally diseased and periodontally healthy patients was a clinical,
      microbiological, and radiographic comparison of teeth and implants and an
      assessment of the implant success rate. METHODS: Thirty-nine partially edentulous
      patients provided with a total of 150 implants were enrolled in the study. Oral
      rehabilitation was undertaken in 15 patients treated for generalized aggressive
      periodontitis (GAgP), 12 patients treated for generalized chronic periodontitis
      (GCP), and 12 periodontally healthy patients. The examinations of the teeth and
      implants were carried out within the framework of a 3-month recall schedule over
      a 3-year period. At each session, clinical parameters for probing depth (PD),
      gingival recession (GR), attachment level (AL), gingival index (GI), and plaque
      index (PI) were recorded, and the composition of the subgingival microflora
      determined by dark-field microscopy. In the periodontally diseased patients,
      Actinobacillus actinomycetemcomitans (A.a.), Porphyromonas gingivalis (P.g.), and
      Prevotella intermedia (P.i.) were detected at teeth and implants by DNA analysis
      in the first and third years after insertion of the superstructure. Intraoral
      radiographs of the teeth and implants were taken at baseline, immediately after
      insertion of the superstructure, and then 1 and 3 years later. RESULTS: The GI
      and PI at implants and teeth remained below 0.25 and 0.6, respectively, in all
      patient groups throughout the study period. At the implants and teeth, a slight
      increase in PD and a continuous attachment loss was recorded in the GAgP
      patients. The attachment loss was greater at the implants than at the teeth in
      all groups. The morphological distribution of the microorganisms revealed
      virtually healthy conditions in all groups. A.a. was detected in two GAgP
      patients, whereas P.g. and P.i. were found more frequently both in the GAgP and
      in the GCP patients. Radiographically detected bone loss was higher after 3 years
      at implants and teeth in the GAgP patients than in the other two groups. The
      implant success rates recorded were 100% in the periodontally healthy and GCP
      patients, and 95.7% in the maxilla and 100% in the mandible of the GAgP patients.
      CONCLUSIONS: The results show that oral rehabilitation can be performed with
      implants in patients treated for generalized aggressive and chronic
      periodontitis. However, slight attachment loss and bone loss were registered at
      the implants and teeth in the patients with aggressive periodontitis.

PMID- 15857094
TI  - Oral health in women with coronary heart disease.
AB  - BACKGROUND: Over the last few decades, oral diseases including periodontitis,
      have been discussed as a possible risk factor for cardiovascular disease. The
      purpose of this study was to compare the oral health of age-matched women with or
      without coronary heart disease (CHD). METHODS: A total of 143 consecutive women,
      aged 43 to 79 years, with diagnosed CHD underwent a thorough dental examination
      including a panoramic radiograph and were compared to 50 women, aged 45 to 77
      years without CHD. RESULTS: The number of remaining teeth and pathological
      periodontal pockets (> or =4 mm) between the groups differed. The women with CHD
      had 18.9 +/- 8.5 remaining teeth versus 23.4 +/- 6.3 teeth in the control group
      (P < 0.001). The CHD group had more pathological periodontal pockets compared to
      the controls, 14.2 +/- 12.4 versus 9.6 +/- 13.3 (P = 0.002), respectively. The
      mean marginal bone level assessed on radiographs was the same in both groups,
      while the number of vertical bone defects differed (P = 0.022). Dentures were
      more frequent in the CHD group than in the controls (27% versus 6%, P = 0.022),
      as was edentulousness, 10.5% versus 0% (P = 0.017), respectively. Multiple
      regression analysis adjusted for age, smoking, body mass index (BMI), diabetes,
      education, and place of birth showed a relation between the number of periodontal
      pockets and CHD with an odds ratio (OR) of 3.8 (1.68 to 8.74), and a tendency
      between dentures and CHD, with an OR of 4.6 (0.99 to 21.28). CONCLUSION: This
      study indicates that women with CHD have worse oral health than those in a
      comparable group with no history of CHD.

PMID- 15857095
TI  - Campylobacter rectus mediates growth restriction in pregnant mice.
AB  - BACKGROUND: Recent studies have suggested that subclinical infection may be an
      important cause of low birth weight. Campylobacters are important human
      pathogens, causing septicemia and occasionally abortion, premature labor, or
      severe perinatal infection. The potential role of oral species of Campylobacter
      in mediating adverse pregnancy outcomes in animal models has not yet been
      determined. Our objective was to determine the effects of Campylobacter rectus
      (C. rectus) infection on pregnancy outcomes in a mouse model. METHODS: On
      embryonic day (E) 7.5, pregnant mice received a subcutaneous, intra-chamber
      challenge with live C. rectus at concentrations of 0, 10(7) or 10(9) colony
      forming units (CFU)/ml. They were sacrificed on E 16.5 and fetuses were evaluated
      for stage of development, weight, and crown-rump length. RESULTS: Dams receiving
      C. rectus had more fetal resorptions after challenge with 10(7) or 10(9) CFU/ml
      (24.1% and 30.1%, respectively) than controls (9%). Higher numbers of growth
      restricted fetuses were also observed in the C. rectus challenged groups (21%) as
      compared to controls (2.3%). Fetuses from dams challenged with 10(9) CFU/ml
      weighed less (0.49 +/- 0.05 g) and had shorter crown-rump lengths (14.69 +/- 0.56
      mm) than controls (0.53 +/- 0.04 g; 15.54 +/- 0.63 mm). C. rectus was detected by
      polymerase chain reaction (PCR) in the placentas from both treated groups and in
      maternal liver tissues from the 10(9) CFU/ml challenged group. CONCLUSIONS:
      Remote subcutaneous maternal C. rectus infection increases fetal resorptions and
      fetal growth restriction in a mouse model. The effects of an oral C. rectus
      infection on pregnancy remain to be determined.

PMID- 15857096
TI  - Risk indicators of periodontal disease in older Thai adults.
AB  - BACKGROUND: The aim of this study was to identify risk indicators for
      periodontitis using cross-sectional data from a group of older Thai adults.
      METHODS: The study group consisted of 2,005 individuals, aged 50 to 73 years old.
      They received detailed medical examinations and periodontal examinations
      including plaque score, probing depth, and clinical attachment level. These
      individuals were categorized into mild, moderate, or severe periodontitis if mean
      clinical attachment level was <2.5 mm, 2.5 to 3.9 mm, or > or = 4.0 mm,
      respectively. The degree of association between the severity of periodontitis and
      various independent variables was investigated using multinomial logistic
      regression analysis. RESULTS: The percentage of subjects classified as mild,
      moderate, and severe periodontitis was 30.5, 53.6, and 15.9, respectively. The
      prevalence of severe periodontitis was higher in males and increased with age. In
      univariate analysis, older subjects, males, less educated persons, persons with
      lower income, persons with higher plaque score, smokers, drinkers, and diabetics
      were more likely to have both moderate and severe periodontitis. In multivariate
      analysis, males, less educated persons, persons with higher plaque score, and
      current smokers were more likely to have moderate periodontitis. Three additional
      factors including older age, former smokers, and diabetes significantly increased
      the odds for having severe periodontitis. Income, alcohol consumption, body mass
      index, and waist circumference had no significant effects on periodontal disease
      severity in the multivariate model. CONCLUSIONS: Our data suggest that age,
      gender, education, oral hygiene status, smoking, and diabetes are significantly
      associated with periodontal disease severity in this study group. Longitudinal
      studies will establish whether these variables are true risk factors.

PMID- 15857097
TI  - The effect of cigarette smoking on the severity of periodontal disease among
      older Thai adults.
AB  - BACKGROUND: The aim of this study is to determine the effect of cigarette smoking
      on the severity of periodontitis in a cross-sectional study of older Thai adults.
      METHODS: The study population consisted of 1,960 subjects (age 50 to 73 years
      old). All subjects received both medical and dental examinations. Periodontal
      examinations, including plaque score, probing depth, and clinical attachment
      level, were done on all teeth present in two diagonal quadrants. Sociodemographic
      characteristics and smoking status were obtained by questionnaires. Multinomial
      logistic regression was used to address the association between cigarette
      consumption and mean clinical attachment level. RESULTS: In this study
      population, 48.7% were non-smokers, 14.4% were current smokers, and 36.9% were
      former smokers. Current smokers had higher percentage of sites with plaque,
      deeper mean probing depth, and greater mean clinical attachment level than former
      smokers and non-smokers. The odds of having moderate and severe periodontitis for
      current smokers were 1.7 and 4.8 times greater than non-smokers, respectively.
      Former smokers were 1.8 times more likely than non-smokers to have severe
      periodontitis. Quitting smoking reduced the odds of having periodontitis. For
      light smokers (<15 packyear), the odds for severe periodontitis reverted to the
      level of non-smokers when they had quit smoking for > or =10 years. For moderate
      and heavy smokers (> or =15 packyear), the odds of having severe periodontitis
      did not differ from those of non-smokers when they had quit smoking for > or =20
      years. CONCLUSIONS: There was a strong association between cigarette smoking and
      the risk of periodontitis among older Thai adults. Quitting smoking appears to be
      beneficial to periodontal health.

PMID- 15857099
TI  - Periodontal conditions in an elderly Japanese population influenced by smoking
      status and serum immunoglobulin G2 levels.
AB  - BACKGROUND: A Japanese population residing in the same area may be suitable for
      evaluation of the association among IgG subclass levels, smoking status, and
      periodontal disease due to similar racial and environmental factors, as these
      factors can interact to influence serum IgG subclass levels. The present cross
      sectional investigation attempted to examine the influence of serum IgG subclass
      levels and smoking status on periodontal condition in a population of elderly
      Japanese subjects. METHODS: Elderly individuals (N = 451, age, 71 years) residing
      in Niigata City, Japan participated in the present study. Clinical evaluations,
      which consisted of probing depth (PD), clinical attachment level (CAL), bleeding
      on probing (BOP), and calculus, and serological determinations including serum
      IgG subclass levels and anti-Porphyromonas gingivalis fimbriae IgG subclass
      titers were conducted. All participants were asked to complete questionnaires
      regarding smoking status and were then divided into one of three groups: never
      smoker, former smoker, or current smoker. RESULTS: Distributions of the number of
      teeth did not differ significantly across the groups. The proportion of sites
      with CAL > or =4 mm (%CAL4) in current smokers was significantly higher in
      comparison with never smokers. Multiple linear regression analysis revealed that
      %CAL4 was influenced by number of teeth, serum IgG2 levels, gender, and smoking
      status (R(2) = 0.253, P < 0.001). The effect of IgG2 was greater than that of
      smoking status. Distribution of IgG2 was not significantly different across the
      three groups. CONCLUSION: These data indicate that serum IgG2 levels influences
      periodontal conditions in an elderly Japanese population independent of smoking
      status.

PMID- 15857098
TI  - Clinical and other risk indicators for early periodontitis in adults.
AB  - BACKGROUND: Periodontal diseases affect over half the adults in the U.S.,
      disproportionately affecting minority populations. Periodontitis can be treated
      in early stages, but it is not clear what features indicate, or could be risk
      factors for, early stages of periodontal attachment loss. This study aimed to
      evaluate associations between clinical and other risk indicators of early
      periodontitis. METHODS: A cross-sectional evaluation of 225 healthy and early
      periodontitis adults aged 20 to 40 years was performed. Clinical measurements,
      demographic information, and smoking histories were recorded. Analyses evaluated
      demographic and clinical associations with health and early periodontitis disease
      categories and periodontal attachment loss. Patterns of attachment loss at
      interproximal and buccal/lingual sites were evaluated. RESULTS: Subject age,
      plaque, and measures of gingivitis exhibited associations with attachment loss
      and probing depth. More periodontal attachment loss was detected in African
      American and Hispanic subjects compared to Asian and Caucasian subjects. Smoking
      history was associated with attachment loss. At interproximal sites, lower molars
      most frequently had attachment loss, whereas at buccal/lingual sites, higher
      proportions of lower bicuspid teeth demonstrated attachment loss compared with
      other sites. CONCLUSIONS: In this study of subjects with minimal attachment loss,
      gingival inflammation was associated with early periodontitis. Lower molar
      interproximal sites were frequently associated with interproximal attachment
      loss, whereas lower bicuspid teeth were at risk for gingival recession on buccal
      surfaces.

PMID- 15857100
TI  - Detection of Actinobacillus actinomycetemcomitans but not bacteria of the red
      complex in aortic aneurysms by multiplex polymerase chain reaction.
AB  - BACKGROUND: Aortic aneurysms affect an increasing number of elderly patients and
      cause considerable morbidity and mortality. The understanding of the mechanisms
      involved in the pathogenesis of aortic aneurysms is unclear and little is known
      about the role of microorganisms in the development of the condition. The aim of
      the present study was to examine aortic aneurysm samples for the presence of four
      putative periodontal pathogens: Actinobacillus actinomycetemcomitans, Treponema
      denticola, Tannerella forsythensis, and Porphyromonas gingivalis. METHODS: Fifty
      six samples from the aneurysm wall were obtained from patients undergoing
      aneurysm repair. DNA was extracted from tissue by conventional methods. Universal
      eubacterial primers for general detection of bacteria and species specific
      primers for detection of the periodontal pathogens were used to amplify part of
      the 16S rRNA gene by polymerase chain reaction (PCR). RESULTS: Bacterial DNA was
      detected in 50 of the 56 aneurysm samples (89.2%). A. actinomycetemcomitans was
      found in four samples (7.1%). None of the samples was positive for T. denticola,
      T. forsythensis, or P. gingivalis. CONCLUSION: Bacteria are commonly present in
      aortic aneurysms and may play a role in the development of the condition.
      Periodontal pathogens are also present.

PMID- 15857101
TI  - Periodontal regenerative potential of autogenous periodontal ligament grafts in
      Class II furcation defects.
AB  - BACKGROUND: The aim of the present study was to evaluate the regenerative
      potential of autogenous periodontal ligament (PDL) grafts in the treatment of
      Class II furcation defects. METHODS: Twenty mandibular Class II furcation defects
      from 10 systemically healthy patients with chronic periodontitis were selected.
      In experimental defects, flaps were coronally positioned following placing
      autogenous PDL grafts that were obtained from third molars; in controls,
      coronally advanced flap procedure without graft was applied. Clinical
      measurements including plaque index, gingival index, probing depth (PD), vertical
      and horizontal clinical attachment level (CAL), and gingival recession (GR) were
      obtained at baseline and after 3 and 6 months postoperatively. Vertical and
      horizontal defect fill was evaluated with open clinical measurements at initial
      surgery and reentry after 6 months. Gingival biopsies from the experimental and
      control defects were obtained at reentry and evaluated histopathologically in
      order to examine the soft tissue response towards PDL grafts. RESULTS: Sites
      treated with PDL grafts demonstrated significant improvement in vertical and
      horizontal defect fill, PD, and CAL at 3 and 6 months compared to presurgical
      values. The difference determined for the PD values of both groups at a
      statistically significant degree in favor of grafted sites was maintained at all
      observation periods. No foreign body reaction was observed in PDL grafts.
      CONCLUSIONS: These short-term results point to the potential of PDL grafts in
      promoting healing of furcation lesions. This preliminary study suggests that the
      use of PDL grafts may have beneficial effects in the treatment of furcation
      defects.

PMID- 15857102
TI  - Randomized study evaluating recombinant human bone morphogenetic protein-2 for
      extraction socket augmentation.
AB  - BACKGROUND: Conventional dentoalveolar osseous reconstruction often involves the
      use of grafting materials with or without barrier membranes. The purpose of this
      study was to evaluate the efficacy of bone induction for the placement of dental
      implants by two concentrations of recombinant human bone morphogenetic protein-2
      (rhBMP-2) delivered on a bioabsorbable collagen sponge (ACS) compared to placebo
      (ACS alone) and no treatment in a human buccal wall defect model following tooth
      extraction. METHODS: Eighty patients requiring local alveolar ridge augmentation
      for buccal wall defects (> or =50% buccal bone loss of the extraction socket) of
      the maxillary teeth (bicuspids forward) immediately following tooth extraction
      were enrolled. Two sequential cohorts of 40 patients each were randomized in a
      double-masked manner to receive 0.75 mg/ml or 1.50 mg/ml rhBMP-2/ACS, placebo
      (ACS alone), or no treatment in a 2:1:1 ratio. Efficacy was assessed by
      evaluating the amount of bone induction, the adequacy of the alveolar bone volume
      to support an endosseous dental implant, and the need for a secondary
      augmentation. RESULTS: Assessment of the alveolar bone indicated that patients
      treated with 1.50 mg/ml rhBMP-2/ACS had significantly greater bone augmentation
      compared to controls (P < or =0.05). The adequacy of bone for the placement of a
      dental implant was approximately twice as great in the rhBMP-2/ACS groups
      compared to no treatment or placebo. In addition, bone density and histology
      revealed no differences between newly induced and native bone. CONCLUSION: The
      data from this randomized, masked, placebo-controlled multicenter clinical study
      demonstrated that the novel combination of rhBMP-2 and a commonly utilized
      collagen sponge had a striking effect on de novo osseous formation for the
      placement of dental implants.

PMID- 15857103
TI  - Modulating the effects of diabetes on osseointegration with aminoguanidine and
      doxycycline.
AB  - BACKGROUND: The current knowledge of wound healing around implant surfaces is
      quite limited, particularly as it relates to the effects of systemic diseases
      such as diabetes. The purpose of our research is to histologically evaluate the
      effects of aminoguanidine and doxycycline in the modification of peri-implant
      wound healing around endosseous implants in diabetic rats. METHODS: Thirty-two
      Sprague-Dawley rats were randomly assigned to four different treatment groups.
      One group served as the non-diabetic control, while diabetes was induced in other
      groups. Titanium plasma-sprayed (TPS) implants were placed in the femora of each
      animal 2 weeks following diabetic induction. One group of diabetic rats was given
      aminoguanidine via intraperitoneal injection, and another given doxycycline via
      oral gavage for 28 days beginning on the day of implantation. The third group of
      diabetic rats received no medication (controls). All animals were sacrificed
      following 28 days of healing. RESULTS: The results were measured by marrow bone
      to implant contact (MBIC) between the groups. Values for MBIC were greater for
      the non-diabetic control group than the diabetic control group (P < 0.001).
      Aminoguanidine-treated diabetic animals had a significantly greater MBIC than the
      diabetic control group (P < 0.01). Diabetic animals receiving doxycycline did not
      differ significantly from the diabetic control group (P > 0.05). CONCLUSIONS: The
      results of this study using a rat model con- firm previous reports that diabetes
      inhibits osseointegration, as defined by MBIC. In addition, this study
      demonstrates that the detrimental effects of diabetes on osseointegration can be
      modified using aminoguanidine systemically. However, systemic administration of
      doxycycline only slightly enhances osseointegration.

PMID- 15857104
TI  - Maintenance of osseointegration utilizing insulin therapy in a diabetic rat
      model.
AB  - BACKGROUND: Normal wound healing processes have been shown to be altered in
      diabetes, and the effect of the diabetes on bone-to-implant contact (BIC) once
      osseointegration has been established is still unknown. The purpose of this study
      was to histologically evaluate the bone-to-implant contact in uncontrolled and
      insulin-controlled rats in which diabetes was induced following the establishment
      of osseointegration. METHODS: Thirty-two rats were assigned to eight different
      treatment groups of four each. Titanium plasma-sprayed (TPS) implants were placed
      in the femora of each animal, and allowed to osseointegrate for 28 days before
      diabetic induction. Daily insulin injections were given to four groups of rats
      and the other four groups received no insulin (uncontrolled). The rats were
      sacrificed at 1, 2, 3, and 4 months following diabetic induction. RESULTS: The
      results indicated that at 1, 2, 3, and 4 months, there was more BIC in the
      insulin-controlled groups compared to the uncontrolled groups. The differences
      were significantly greater at 2, 3, and 4 months (P < or =0.001). CONCLUSIONS:
      This study demonstrated that osseointegrated dental implants in insulin
      controlled diabetic rats maintained bone-to-implant contacts over a 4-month
      period. However, boneto- implant contact appears to decrease with time in
      uncontrolled diabetic rats.

PMID- 15857105
TI  - The effectiveness of 1% pimecrolimus cream in the treatment of oral erosive
      lichen planus.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy, relative
      safety, and tolerability of 1% pimecrolimus cream in the treatment of oral
      erosive lichen planus (OELP). METHODS: Twenty patients with OELP were randomized
      into equal groups; group 1 applied 1% pimecrolimus cream twice daily to their
      oral lesions for 4 weeks, whereas group 2 applied a placebo cream. Photographs of
      the lesions were taken and analyzed for areas of ulceration, erythema, and
      reticulation. Discomfort scores were also assessed with a visual analogue scale
      (VAS). Blood samples were taken at baseline and at study completion; a complete
      blood count with differential and comprehensive metabolic panel was ordered. The
      Wilcoxon signed rank test was used. RESULTS: The experimental group showed a
      decrease in ulceration (alpha = 0.068) and erythema (alpha = 0.005) at the mid
      point with continued reduction of erythema at the final (alpha = 0.075) time
      measurement. The control group demonstrated an increase in reticulation at the
      mid-point (alpha = 0.017) and final (alpha = 0.007) time measurement. The VAS
      scores for the experimental group decreased during the study (alpha = 0.022).
      Blood levels were within the normal range. CONCLUSIONS: The OELP lesion size in
      the 1% pimecrolimus group decreased and the pimecrolimus cream was found to
      significantly reduce the patient's pain scores. Further study of 1% pimecrolimus
      as therapy for OELP is warranted since it was shown to be effective, relatively
      safe, and well tolerated by patients within the limits of this short-term study.

PMID- 15857106
TI  - Intraoral autogenous block onlay bone grafting for extensive reconstruction of
      atrophic maxillary alveolar ridges.
AB  - BACKGROUND: Endosseous implants require sufficient bone volume for complete bone
      coverage. Alveolar deficiency can prevent ideal implant placement. Local bone
      grafts are a convenient source of autogenous bone in alveolar reconstruction. The
      aim of this study was to describe a technique, and to evaluate the success of
      extensive bone reconstruction of atrophic maxillary alveolar ridges using only
      intraoral block bone grafts prior to dental implantation. METHODS: Files of 10
      healthy patients with extensive bone reconstruction of the maxillary alveolar
      ridge using intraoral block bone graft operations were reviewed. Medical history,
      smoking status, bone origin (donor sites), number of bone blocks, and
      complications were recorded. RESULTS: Of the 10 extensive bone maxillary
      reconstructions, four were uneventful, two required additional bone augmentation
      at the time of dental implant placement, two had a minimal graft exposure, one
      had a minor adverse effect (temporary paresthesia), and one operation partially
      failed and required partial graft removal. CONCLUSION: Intraoral bone block
      grafting is a predictable operation with a high success rate for long-span
      augmentation, up to complete jaw augmentation/ extensive bone reconstruction of
      the maxillary alveolar ridge.

PMID- 15857107
TI  - Orthodontic treatment in a patient with Papillon-Lefevre syndrome.
AB  - BACKGROUND: Report of a combined periodontal and orthodontic treatment in a
      patient with Papillon-Lefevre Syndrome (PLS). METHODS: A patient with PLS was
      treated orthodontically 26 months after the start of a combined mechanical and
      antibiotic therapy. Clinical periodontal parameters were obtained 26 (t1), 60
      (t2), and 79 (t3) months after anti-infective therapy. The deepest site of each
      tooth was sampled for microbiological analysis at 26 and 60 months. Periodontal
      maintenance therapy was provided every 6 weeks. After a stable periodontal
      situation was achieved, orthodontic treatment, consisting of space opening for
      the upper canines with a multibracket appliance and coil springs, was carried
      out. In the lower jaw, crowding was resolved by an orthodontic mesialization of
      the canines. RESULTS: Twenty-six months (t1) after the beginning of the combined
      mechanical and antibiotic therapy, 6% of the sites exhibited 4 mm probing depth
      (PD) with bleeding on probing (BOP) or PD > or =5 mm. Sixty months (t2) after
      therapy the number of sites with 4 mm PD with BOP or PD > or =5 mm had increased
      to 17%, and 79 months after therapy (t3) 13% of all sites were similarly
      affected. From 26 to 60 months, a slight mean clinical attachment level (CAL)
      gain was observed, whereas the mean PD increased. From 60 to 79 months, there was
      a mean PD reduction. However, a significant mean attachment loss was also noted.
      After 26 months (t1), RNA probes failed to detect A. actinomycetemcomitans, P.
      gingivalis, or T. forsythensis from any site. Thirty-four months later (t2),
      subgingival recolonization was observed. A. actinomycetemcomitans was detected by
      RNA probes at three sites. At 26 and 60 months (t1, t2), trypticase-soy with
      serum, bacitracin, and vancomycin (TSBV) culture failed to detect A.
      actinomycetemcomitans at any of the sampled sites. Eighty-two months after the
      beginning of therapy (t4), none of the applied methods could detect A.
      actinomycetemcomitans from the pooled samples from the deepest pockets of each
      quadrant or the oral mucosa. In the present case, concomitant orthodontic
      treatment with a fixed appliance could be performed without further pronounced
      periodontal deterioration. Space for eruption of the canines and premolars was
      created, in addition to an alignment of the teeth. CONCLUSION: After a successful
      combined mechanical and antibiotic periodontal therapy of the PLS periodontitis,
      moderate orthodontic tooth movements may be possible within a complex
      interdisciplinary treatment regimen.

PMID- 15857108
TI  - Perioral angioedema associated with angiotensin-converting enzyme inhibitor.
AB  - BACKGROUND: Angioedema is a non-pruritic swelling usually limited to the skin and
      mucous membranes of the face and perioral soft tissues. It can be life
      threatening but usually is not, and can be managed with conservative medical
      treatment unless the airway is endangered. Recent reports suggest that
      angiotensin-converting enzyme (ACE) inhibitors can predispose and/or precipitate
      angioedema, with a predilection toward patients of African American ancestry.
      METHODS: This case report involved a 65-year-old African American female who was
      being treated surgically for localized chronic periodontitis. The procedure was
      performed without incident, and the patient was alert and stable when released.
      The next day, the patient called and reported that her lips were swollen. She
      stated that this had happened a number of times over the past several years,
      sometimes related to eating shellfish and other times without any known
      precipitating factor. All previous episodes of perioral swelling occurred after
      ACE inhibitor therapy had been initiated. RESULTS: The patient was in no
      distress, with no other site involvement. She was prescribed oral hydroxyzine and
      her appearance returned to normal after 5 days. Although the patient had
      experienced previous episodes of angioedema, none had been in response to any
      dental procedure. She was referred to the Allergy and Immunology Clinic for skin
      testing, the results of which were negative to shellfish with good controls.
      Other potentiating etiologies were also ruled out by the allergist. CONCLUSIONS:
      Angioedema is a recognized possible side effect of ACE inhibitor therapy. The
      exact mechanism by which ACE inhibitors induce angioedema is not known, although
      the risk of occurrence is much greater in African Americans. Practitioners should
      be alert to this potentially fatal condition in patients who take ACE inhibitors
      or the newer angiotensin II receptor blockers (ARBs).

PMID- 15857109
TI  - Interdental papilla augmentation procedure following orthodontic treatment in a
      periodontal patient.
AB  - BACKGROUND: The absence of the interdental papilla is a situation that may alter
      patients' esthetics. Recession of interproximal gingival tissues may be a
      consequence of periodontal disease, but in some cases it may also be a
      consequence of periodontal therapy, as a result of surgical or non-surgical
      procedures. METHODS: The authors present a new multidisciplinary approach for the
      treatment of migrated maxillary incisors presenting infrabony defects, extrusion,
      and loss of the interdental papilla. RESULTS AND CONCLUSION: The proposed
      clinical protocol may reconstruct the interproximal soft tissue, with esthetic
      improvement of the papillary level, together with resolution of the periodontal
      defects.

PMID- 15857110
TI  - Discovery of a beta-MSH-derived MC-4R selective agonist.
AB  - A series of novel, disulfide-constrained human beta-melanocyte stimulating
      hormone (beta-MSH)-derived peptides were optimized for in vitro melanocortin-4
      receptor (MC-4R) binding affinity, agonist efficacy, and selectivity. The most
      promising of these, analogue 18, was further studied in vivo using chronic rat
      food intake and body weight models.

PMID- 15857111
TI  - Synthesis and biological evaluation of aminopolyamines.
AB  - Exploitation of the polyamine backbone as a vector for intracellular transport of
      various pharmacophores has focused largely on fixing the cargo molecule to one of
      the nitrogens in the linear chain. This communication describes the assembly of a
      model aminopolyamine analogue, 6-amino-N(1),N(12)-diethylspermine, and its
      biological properties. This amino polyamine presents an additional site of
      attachment for cargo molecules, reduces cell growth, and achieves cellular
      concentrations that are higher than those of N(1),N(12)-diethylspermine.

PMID- 15857112
TI  - Discovery of diphenyloxazole and Ndelta-Z-ornithine derivatives as highly potent
      and selective human prostaglandin EP(4) receptor antagonists.
AB  - Two novel classes of diphenyloxazole and Ndelta-Z-ornithine derivatives as highly
      potent and selective EP(4) antagonists have been discovered. The optimized
      diphenyloxzole 8 and Ndelta-Z-ornithine 11 effectively competed with [(3)H]PGE(2)
      binding to human recombinant EP(4), with K(i) values of 0.30 nM and 0.91 nM,
      respectively, and were selective for all members of the human prostanoid receptor
      family. 8 was shown to exhibit good pharmacokinetic properties in rats and dogs
      and potent inhibitory activity toward in vitro PGE(2)-promoted IgE synthesis.

PMID- 15857113
TI  - Identification and structure-activity relationship of phenolic acyl hydrazones as
      selective agonists for the estrogen-related orphan nuclear receptors ERRbeta and
      ERRgamma.
AB  - The first small molecule agonists of the estrogen-related receptors have been
      identified. GSK4716 (3) and GSK9089 (4) show binding to ERRgamma with remarkable
      selectivity over the classical estrogen receptors. Notably, in cell-based
      reporter assays, 3 mimics the protein ligand PGC-1alpha in activation of human
      ERRbeta and ERRgamma.

PMID- 15857114
TI  - Toward a novel class of antithrombotic compounds with dual function. Discovery of
      1,4-benzoxazin-3(4H)-one derivatives possessing thrombin inhibitory and
      fibrinogen receptor antagonistic activities.
AB  - A novel class of potential antithrombotic compounds with moderate thrombin
      inhibitory and fibrinogen receptor antagonistic activity is described.
      Combination of anticoagulant and antiaggregatory activity in the same molecular
      entity is presented as a new promising approach in the search for novel
      antithrombotic agents.

PMID- 15857115
TI  - Thyroid receptor ligands. 3. Design and synthesis of 3,5-dihalo-4
      alkoxyphenylalkanoic acids as indirect antagonists of the thyroid hormone
      receptor.
AB  - Based on the recently described concept of "indirect antagonism" of nuclear
      receptors, a series of thyroid hormone receptor (TR) antagonists were prepared,
      in which the outer ring of a thyromimetic was replaced with alkyl chains of
      variable length and branch. The results of a binding assay for the human TR and
      reporter cell assay revealed, within this series, a positive correlation between
      increasing bulk of the alkyl group and affinity to TRs. Compared with already
      reported TR antagonists, their affinities are within the same range, thus
      potentially representing a useful approach to novel and high affinity TR
      antagonists.

PMID- 15857116
TI  - 1-(5-Chloro-2-alkoxyphenyl)-3-(5-cyanopyrazin-2-yl)ureas [correction of
      cyanopyrazi] as potent and selective inhibitors of Chk1 kinase: synthesis,
      preliminary SAR, and biological activities.
AB  - The discovery of 1-(5-chloro-2-alkoxyphenyl)-3-(5-cyanopyrazin-2-yl)ureas as a
      new class of potent (IC(50) values of 3-10 nM) and selective inhibitors of Chk1
      kinase was described. One of these compounds (2e) potentiates HeLa cells by over
      22-fold against doxorubicin in an antiproliferation assay, and SW620 cells
      against camptothecin by 20-fold in an antiproliferation assay and 14-fold in a
      soft agar assay. Flow cytometry (FACS) analysis confirmed that 2e abrogated G2
      checkpoint arrest of H1299 cells caused by doxorubicin and S checkpoint arrest
      caused by camptothecin.

PMID- 15857117
TI  - "In situ cross-docking" to simultaneously address multiple targets.
AB  - In standard docking, every target structure requires separate docking
      calculations. To overcome this limitation, an approach is presented by which
      multiple proteins can be addressed simultaneously in a single docking run. This
      "in situ cross-docking" is built on a grid-based docking method and follows the
      idea that grids calculated for single binding sites may be joined to one common
      grid. Docking then allows for a direct selection of the optimal target by the
      ligand being docked. The approach is technically feasible and can lead to
      significant time savings over conventional cross-docking.

PMID- 15857118
TI  - Thermodynamic analysis of interactions between N-linked sugar chains and F-box
      protein Fbs1.
AB  - Fbs1 is a recently discovered F-box protein that was proposed to recognize high
      mannose-type asparagine-linked glycoprotein sugar chains. To reveal the
      specificity of Fbs1, Manalpha1-->6Manbeta1-->4GlcNAc(2), Manalpha1-->3Manbeta1-
      >4GlcNAc(2), and Manalpha1-->3(Manalpha1--> 6)Manbeta1-->4GlcNAc(2) were
      synthesized and their affinities for Fbs1 were evaluated in comparison with
      previously synthesized Man(9)GlcNAc(2) and Man(8)GlcNAc(2). These analyses
      revealed that Man(3)GlcNAc(2) had the strongest affinity and the chitobiose and
      alpha1-->6 linked Man residue are necessary for Fbs1 to recognize a sugar.

PMID- 15857119
TI  - Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo
      investigations.
AB  - We have investigated the activity of 60 bisphosphonates against the replication
      of Toxoplasma gondii in vitro and of three of the most active compounds, in vivo.
      The two most active compounds found were n-alkyl bisphosphonates containing long
      (n = 9 or 10) hydrocarbon chains, not the nitrogen-containing species used in
      bone resorption therapy. The target of all of the most active bisphosphonates
      appears to be the isoprene biosynthesis pathway enzyme farnesyl pyrophosphate
      synthase (FPPS), as indicated by the correlations between T. gondii growth
      inhibition and FPPS (human and Leishmania major) enzyme inhibition and by the
      fact that a T. gondii strain engineered to overexpress FPPS required considerably
      higher levels of bisphosphonates to achieve 50% growth inhibition, while the
      IC(50) for atovaquone (which does not inhibit FPPS) remained the same in the
      overexpressing strain. The phosphonate inhibitor of the non-mevalonate pathway,
      fosmidomycin, which inhibits the enzyme 1-deoxyxylulose-5-phosphate
      reductoisomerase, had no effect on T. gondii growth. To investigate structure
      activity relationships (SARs) in more detail, we used two three-dimensional
      quantitative SAR methods: comparative molecular field analysis (CoMFA) and
      comparative molecular similarity indices analysis (CoMSIA), to investigate all 60
      bisphosphonates. Both the CoMFA and CoMSIA models indicated a 60-70% contribution
      from steric interactions and a 30-40% contribution from electrostatic
      interactions and using four N = 55 training sets for each method, we found on
      average between a factor of 2 and 3 error in IC(50) prediction. The three most
      active compounds found in vitro were tested in vivo in a Smith-Webster mouse
      model and the two most active bisphosphonates were found to provide up to an 80%
      protection from death, a considerable improvement over that found previously with
      nitrogen-containing bisphosphonates. This effect may originate in the much higher
      therapeutic indices of these alkyl bisphosphonates, as deduced from in vitro
      assays using LD(50) values for growth inhibition of a human cell line. Overall,
      these results indicate that alkyl bisphosphonates are promising compounds for
      further development as agents against Toxoplasma gondii growth, in vivo.

PMID- 15857120
TI  - Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid
      (lidorestat) and congeners as highly potent and selective inhibitors of aldose
      reductase for treatment of chronic diabetic complications.
AB  - Recent efforts to identify treatments for chronic diabetic complications have
      resulted in the discovery of a novel series of highly potent and selective 3
      [(benzothiazol-2-yl)methyl]indole-N-alkanoic acid aldose reductase inhibitors.
      The lead candidate, 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic
      acid (lidorestat, 9) inhibits aldose reductase with an IC(50) of 5 nM, while
      being 5400 times less active against aldehyde reductase, a related enzyme
      involved in the detoxification of reactive aldehydes. It lowers nerve and lens
      sorbitol levels with ED(50)'s of 1.9 and 4.5 mg/kg/d po, respectively, in the 5
      day STZ-induced diabetic rat model. In a 3-month diabetic intervention model (1
      month of diabetes followed by 2 months of drug treatment at 5 mg/kg/d po), it
      normalizes polyols and reduces the motor nerve conduction velocity deficit by 59%
      relative to diabetic controls. It has a favorable pharmacokinetic profile (F,
      82%; t(1/2), 5.6 h; Vd, 0.694 L/kg) with good drug penetration in target tissues
      (C(max) in sciatic nerve and eye are 2.36 and 1.45 mug equiv/g, respectively,
      when dosed with [(14)C]lidorestat at 10 mg/kg po).

PMID- 15857121
TI  - Morphiceptin analogues containing a dipeptide mimetic structure: an investigation
      on the bioactive topology at the mu-receptor.
AB  - We describe the design, the conformational behavior, and the biological activity
      at the mu-opioid receptor of new morphiceptin analogues. In these analogues a
      recently described dipeptide mimetic structure replaces both the N- and the C
      terminal Xaa-Pro dipeptide of morphiceptin. Conformational investigation on the
      most active analogue, compared to the parent peptide, indicates a high degree of
      structural tolerance within the mu-opioid receptor binding site. In fact, our
      results indicate that only the location and the relative orientation of the side
      chains of the aromatic pharmacophoric residues represent the indispensable
      structural features for mu-receptor binding. To reach such topological
      arrangement, opioid peptides can adopt different conformations and
      configurations. In particular, opioid peptides bearing a proline residue as
      spacer between the two aromatic residues can adopt, in the active state, both cis
      and trans configurations at the Tyr(1)-Pro(2) amide bond, each of them with the
      appropriate backbone and side chains orientations.

PMID- 15857122
TI  - A bioavailability score.
AB  - Responding to a demonstrated need for scientists to forecast the permeability and
      bioavailability (F) properties of compounds before their purchase, synthesis, or
      advanced testing, we have developed a score that assigns the probability that a
      compound will have F > 10% in the rat. Neither the rule-of-five, log P, log D,
      nor the combination of the number of rotatable bonds and polar surface area
      successfully categorized compounds. Instead, different properties govern the
      bioavailability of compounds depending on their predominant charge at biological
      pH. The fraction of anions with >10% F falls from 85% if the polar surface area
      (PSA) is < or = 75 A(2), to 56% if 75 < PSA < 150 A(2), to 11% if PSA is > or =
      150 A(2). On the other hand, whereas 55% of the neutral, zwitterionic, or
      cationic compounds that pass the rule-of-five have >10% F, only 17% of those that
      fail have > 10% F. This same categorization distinguishes compounds that are
      poorly permeable from those that are permeable in Caco-2 cells. Further
      validation is provided with human bioavailability values from the literature.

PMID- 15857123
TI  - Enantiomerically pure hexahydropyrazinoquinolines as potent and selective
      dopamine 3 subtype receptor ligands.
AB  - We report the design and synthesis of a series of enantiomerically pure
      hexahydropyrazinoquinolines as potent and selective ligands for the dopamine 3
      subtype receptor using a newly developed synthetic method and using in vitro
      pharmacological evaluation. Our efforts yielded optically pure ligands with high
      affinities for the D(3) receptor and outstanding selectivity over closely related
      D(1)-like and D(2)-like receptors. For example, compound 38a has a K(i) value of
      5.7 nM to the D(3) receptor and selectivity greater than 10000- and 1600-fold
      over the D(1)-like and D(2)-like receptors, respectively, and thus is one of the
      most selective D(3) ligands reported to date.

PMID- 15857124
TI  - HierS: hierarchical scaffold clustering using topological chemical graphs.
AB  - An exhaustive ring-based algorithm, HierS, has been developed in order to provide
      an intuitive approach to compound clustering for analyzing high-throughput
      screening results. The recursive algorithm rapidly identifies all possible ring
      delimited substructures within a set of compounds. Molecules are grouped by
      shared ring substructures (scaffolds) so that common scaffolds obtain higher
      membership. Once all of the scaffolds for a set of compounds are identified, the
      hierarchical structural relationships between the scaffold structures are
      established. The complex network of hierarchical relationships is then utilized
      to navigate compounds in a structurally directed fashion. When the scaffold
      hierarchy is traversed, over-represented structural features can be rapidly
      identified so that excess compounds that contain them can be removed without
      significantly impacting the structural diversity landscape of the compound set.
      Furthermore, the removed compounds can provide the opportunity to follow-up on
      active compounds that had previously been discarded because of practical
      limitations on follow-up capacity. A Web-based interface has been developed that
      incorporates this algorithm in order to allow for an interactive analysis. In
      addition, biological data are coupled to scaffolds by the inclusion of activity
      histograms, which indicate how the compounds in each scaffold class performed in
      previous high-throughput screening campaigns.

PMID- 15857125
TI  - Synthesis and antibacterial activity of 1-(2-fluorovinyl)-7-substituted-4
      quinolone-3-carboxylic acid derivatives, conformationally restricted analogues of
      fleroxacin.
AB  - The novel 1-(2-fluorovinyl)-4-quinolone-3-carboxylic acid derivatives Z-15a-c, E
      15a-c, Z-16a-c, and E-16a-c, conformationally restricted analogues of fleroxacin
      (5), were synthesized, and their in vitro antibacterial activity was evaluated. A
      dehydrosulfenylation of a 2-fluoro-2-[(4-methoxyphenyl)sulfinyl]ethyl group was
      employed as a key step for the construction of a 2-fluorovinyl group at the N-1
      position. It appeared evident that the Z-isomers Z-15a-c and Z-16a-c exhibited 2-
      to 32-fold more potent in vitro antibacterial activity than the corresponding E
      isomers E-15a-c and E-16a-c. Furthermore, since Z-15b showed in vitro
      antibacterial activity and DNA gyrase inhibition comparable to that of 5, it was
      hypothesized that the conformation of Z-15b would be equivalent to the active
      conformer of 5. The results revealed that the antibacterial Z-1-(2
      fluorovinyl)quinolone derivatives carry the novel N-1 substituent of the
      fluoroquinolones.

PMID- 15857126
TI  - Successful in silico discovery of novel nonsteroidal ligands for human sex
      hormone binding globulin.
AB  - Using "in silico" drug design methodologies, we have discovered several
      nonsteroidal compounds of natural origin that bind to human sex hormone binding
      globulin (SHBG) with affinity constants of 0.1 x 10(6) to 1.2 x 10(6) M(-1). The
      computational solutions we developed involved pharmacophore-aided database
      search, virtual protein-ligand docking, and structure-activity modeling with
      "inductive" QSAR descriptors. By screening 23 836 natural substance structures,
      we identified 29 potential SHBG ligands, and eight of these bound the protein in
      vitro. These nonsteroidal ligands belong to four classes of molecular scaffolds
      with several available substitution positions that could allow chemical
      modification to enhance SHBG-binding activity. Interestingly, one of these
      compounds is structurally similar to a dicyclohexane derivative that binds to rat
      SHBG and causes azospermia when administered to male rats. Taken together, the in
      silico strategy we have developed will aid in the discovery of nonsteroidal
      ligands of SHBG with novel pharmacological properties.

PMID- 15857127
TI  - DASH: a novel analysis method for molecular dynamics simulation data. Analysis of
      ligands of PPAR-gamma.
AB  - A novel molecular dynamics (MD) analysis algorithm, DASH, is introduced in this
      paper. DASH has been developed to utilize the sequential nature of MD simulation
      data. By adjusting a set of parameters, the sensitivity of DASH can be
      controlled, allowing molecular motions of varying magnitudes to be detected or
      ignored as desired, with no knowledge of the number of conformations required
      being prerequisite. MD simulations of three synthetic ligands of the orphan
      nuclear receptor PPARgamma were generated in vacuo using Tripos's SYBYL and used
      as the training set for DASH. Two X-ray crystal structures of PPARgamma complexed
      with Rosiglitazone were compared to gain knowledge of the pharmacophoric
      conformation; this showed that the conformation of the ligand is significantly
      different between the two structures, indicating that there is no distinct
      conformation in which rosiglitazone binds to PPARgamma but multiple binding
      modes. An investigation into simulation length was carried out. A simulation of 5
      ns was found to give highly variable results, whereas a simulation of 25 ns gave
      a representative window of motion for molecules of this size. DASH was compared
      with Ward's hierarchical cluster analysis method. The results show that DASH
      analysis is as good as Ward analysis in some areas (e.g. conformation
      identification) and is superior in others (e.g. speed and input size).

PMID- 15857128
TI  - Frontal affinity chromatography with MS detection of EphB2 tyrosine kinase
      receptor. 2. Identification of small-molecule inhibitors via coupling with
      virtual screening.
AB  - We have integrated two complementary methods, high-throughput virtual screening
      with a "high-content" wet screening technique based on frontal affinity
      chromatography with mass spectrometry detection (FAC-MS), for identification of
      hits against the erythropoietin-producing hepatocellular B2 (EphB2) receptor
      tyrosine kinase domain. Both an EphB2-directed virtual screen combining docking
      and scoring and a kinase-directed pharmacophore search strategy were used to
      identify a compound set enriched in bioactive compounds against EphB2. The
      coupling of virtual screening methodologies with FAC-MS is a unique hybrid
      approach that can be used to increase the efficacy of both hit discovery and
      optimization efforts in drug discovery and has successfully identified hits, in
      particular 19a (36% shift, IC(50) = 5.2 microM, K(d) = 3.3 microM), as inhibitors
      for EphB2, a potential cancer target.

PMID- 15857129
TI  - On the binding of indeno[1,2-c]isoquinolines in the DNA-topoisomerase I cleavage
      complex.
AB  - An ab initio quantum mechanics calculation is reported which predicts the
      orientation of indenoisoquinoline 4 in the ternary cleavage complex formed from
      DNA and topoisomerase I (top1). The results of this calculation are consistent
      with the hypothetical structures previously proposed for the indenoisoquinoline
      DNA-top1 ternary complexes based on molecular modeling, the crystal structure of
      a recently reported ternary complex, and the biological results obtained with a
      pair of diaminoalkyl-substituted indenoisoquinoline enantiomers. The results of
      these studies indicate that the pi-pi stacking interactions between the
      indenoisoquinolines and the neighboring DNA base pairs play a major role in
      determining binding orientation. The calculation of the electrostatic potential
      surface maps of the indenoisoquinolines and the adjacent DNA base pairs shows
      electrostatic complementarity in the observed binding orientation, leading to the
      conclusion that electrostatic attraction between the intercalators and the base
      pairs in the cleavage complex plays a major stabilizing role. On the other hand,
      the calculation of LUMO and HOMO energies of indenoisoquinoline 13b and
      neighboring DNA base pairs in conjunction with NBO analysis indicates that charge
      transfer complex formation plays a relatively minor role in stabilizing the
      ternary complexes derived from indenoisoquinolines, DNA, and top1. The results of
      these studies are important in understanding the existing structure-activity
      relationships for the indenoisoquinolines as top1 inhibitors and as anticancer
      agents, and they will be important in the future design of indenoisoquinoline
      based top1 inhibitors.

PMID- 15857130
TI  - Ligand-based prediction of active conformation by 3D-QSAR flexibility descriptors
      and their application in 3+3D-QSAR models.
AB  - A conceptionally new 3D molecular descriptor type and methodology are deduced by
      simple statistical thermodynamic reasoning, based on the free energy change
      encountered during a transformation of a conformational ensemble of the ligand to
      an active conformation. The performance of the descriptor was first tested on 37
      endomorphin analogues with mu-opiate activity. The method resulted in predictive
      3D-QSAR models, and the active conformation was also predicted. Generally, the
      methodology can be combined with the traditional 3D-QSAR techniques in a 3+3D
      QSAR manner. This feature was tested on a series of 38 PGF2alphaprostaglandin
      analogues with antinidatory activity; the extent to which the molecular
      flexibility explains the variation in the biological activity was estimated and
      the active conformation was predicted. The novel descriptors in combination with
      the grid-based SOMFA descriptors resulted in 3+3D-QSAR models with good levels of
      predictivity leading to the approach of separation of the effect of the molecular
      interaction field of the active conformation and the effect of the conformational
      free energy loss.

PMID- 15857131
TI  - Molecular dynamics simulation of the ligand binding domain of farnesoid X
      receptor. Insights into helix-12 stability and coactivator peptide stabilization
      in response to agonist binding.
AB  - The dynamic changes which take place in the ligand binding domain (LBD) of
      farneosid X receptor (FXR) in response to agonist binding and in the presence of
      coactivator peptides were studied with nanosecond time-scale molecular dynamics.
      Four different systems were analyzed, including the holo-LBD complexed with
      6ECDCA, the holo-LBD in the presence of two coactivator peptides, and two
      artificial apo forms, with and without coactivator peptides. Our results revealed
      a detailed picture of the differential micro- and macromodifications occurring in
      the LBD in the presence or not of the agonist molecule and the coactivator
      peptides. In the apo simulation a major conformational change took place in the
      crucial helix 12, while the holo-LBD was globally stabilized by the ligand. When
      the coactivator peptides were included in the simulation, a clear agonist-induced
      stabilization was observed for the canonical peptide. Interestingly, the second
      peptide was released from the holo-LBD while it was kept bound in the apo
      simulation. The present results provide a molecular basis for the understanding
      the role played by the bile acid agonist in receptor stabilization and enhanced
      cofactor recruitments.

PMID- 15857132
TI  - Synthesis and cytotoxic evaluation of combretafurazans.
AB  - Combretastatin A-4 is an antitumoral and antitubulin agent that is active only in
      its cis configuration. In the present manuscript, we have synthesized cis-locked
      combretastatins embodying a furazan ring (combretafurazans). To achieve this, we
      have developed a new strategy that exploits the dehydration of vicinal dioximes
      using the Mitsunobu reaction. Among the advantages of following such a strategy
      are the mild conditions used for the construction of the diarylfurazan
      derivatives, allowing for the presence of highly functionalized substrates and
      deactivated aromatic rings. Combretafurazans are more potent in vitro cytotoxic
      compounds compared to combretastatins in neuroblastoma cells, yet maintaining
      similar structure-activity relationship and pharmacodynamic profiles.

PMID- 15857133
TI  - Calculating virtual log P in the alkane/water system (log P(N)(alk)) and its
      derived parameters deltalog P(N)(oct-alk) and log D(pH)(alk).
AB  - Growing interest in the use of both the logarithm of the partition coefficient of
      the neutral species in the alkane/water system (log P(N)(alk)) and the difference
      between log P(N)(oct) (the logarithm of the partition coefficient of the neutral
      species in the n-octanol/water system) and log P(N)(alk) (Deltalog P(N)(oct-alk))
      in the early stages of drug design has stimulated development of a computational
      tool based on the Volsurf software to predict virtual (=of each conformer) log
      P(N)(alk) and virtual log P(N)(oct). From these two pieces of data, it is then
      possible to calculate Deltalog P(N)(oct-alk) for a given compound as the
      difference between log P(N)(oct) and log P(N)(alk). Once the pK(a) is known and
      the legitimacy of neglecting the contribution made by the ionized species has
      been checked, it is also possible to calculate log D(pH)(alk), which might be an
      important lipophilicity descriptor in absorption, distribution, metabolism, and
      excretion (ADME) prediction, from log P(N)(alk).

PMID- 15857134
TI  - Identification of novel low molecular weight CXCR4 antagonists by structural
      tuning of cyclic tetrapeptide scaffolds.
AB  - A highly potent CXCR4 antagonist, compound 2, was previously found by using two
      orthogonal cyclic pentapeptide libraries involving conformation-based and
      sequence-based libraries based on the pharmacophore of a 14-mer peptidic
      antagonist, 1. Herein, cyclic tetrapeptides derived from replacements of the
      dipeptide unit (Nal-Gly) with a gamma-amino acid and pseudopeptides cyclized by
      disulfide and olefin bridges were synthesized to find novel scaffold structures
      different from that of cyclic pentapeptides. These compounds contain a reduced
      number of peptide bonds compared to compound 2. Furthermore, several analogues
      with chemical modification of the side chain of Arg(4) in 2 were also prepared.
      From these, several new leads possessing high to moderate CXCR4-antagonistic
      activity were characterized.

PMID- 15857135
TI  - Structural requirements for factor Xa inhibition by 3-oxybenzamides with neutral
      P1 substituents: combining X-ray crystallography, 3D-QSAR, and tailored scoring
      functions.
AB  - The design, synthesis, and structure-activity relationship of 3-oxybenzamides as
      potent inhibitors of the coagulation protease factor Xa are described on the
      basis of X-ray structures, privileged structure motifs, and SAR information. A
      total of six X-ray structures of fXa/inhibitor complexes led us to identify the
      major protein-ligand interactions. The binding mode is characterized by a
      lipophilic dichlorophenyl substituent interacting with Tyr228 in the protease S1
      pocket, while polar parts are accommodated in S4. This alignment in combination
      with docking allowed derivation of 3D-QSAR models and tailored scoring functions
      to rationalize biological affinity and provide guidelines for optimization. The
      resulting models showed good correlation coefficients and predictions of external
      test sets. Furthermore, they correspond to binding site topologies in terms of
      steric, electrostatic, and hydrophobic complementarity. Two approaches to derive
      tailored scoring functions combining binding site and ligand information led to
      predictive models with acceptable predictions of the external set. Good
      correlations to experimental affinities were obtained for both AFMoC (adaptation
      of fields for molecular comparison) and the novel TScore function. The SAR
      information from 3D-QSAR and tailored scoring functions agrees with all
      experimental data and provides guidelines and reasonable activity estimations for
      novel fXa inhibitors.

PMID- 15857136
TI  - Conformation mining: an algorithm for finding biologically relevant
      conformations.
AB  - Discovering essential features shared by active compounds, an important step in
      drug-design, is complicated by conformational flexibility. We present a new
      algorithm to efficiently mine the conformational space of multiple actives and
      find small subsets of conformations likely to be biologically relevant. The
      approach identifies chemical and steric similarities between actives, providing
      insight into features important for binding when structural data are absent.
      Validation studies (thrombin and CDK2 data) produce alignments similar to protein
      based alignments.

PMID- 15857137
TI  - Structure-activity relationships of fluorinated lysophosphatidic acid analogues.
AB  - Lysophosphatidic acid (LPA, 1- or 2-acyl-sn-glycerol 3-phosphate) displays an
      intriguing cell biology that is mediated via interactions with seven
      transmembrane G-protein-coupled receptors (GPCRs) and the nuclear hormone
      receptor PPARgamma. To identify receptor-selective LPA analogues, we describe a
      series of fluorinated LPA analogues in which either the sn-1 or sn-2 hydroxyl
      group was replaced by a fluoro or fluoromethyl substituent. We also describe
      stabilized phosphonate analogues in which the bridging oxygen of the
      monophosphate was replaced by an alpha-monofluoromethylene (-CHF-) or alpha
      difluoromethylene (-CF(2)-) moiety. The sn-2- and sn-1-fluoro-LPA analogues were
      unable to undergo acyl migration, effectively "freezing" them in the sn-1-O-acyl
      or sn-2-O-acyl forms, respectively. We first tested these LPA analogues on insect
      Sf9 cells induced to express human LPA(1), LPA(2), and LPA(3) receptors. While
      none of the analogues were found to be more potent than 1-oleoyl-LPA at LPA(1)
      and LPA(2), several LPA analogues were potent LPA(3)-selective agonists. In
      contrast, 1-oleoyl-LPA had similar activity at all three receptors. The alpha
      fluoromethylene phosphonate analogue 15 activated calcium release in LPA(3)
      transfected insect Sf9 cells at a concentration 100-fold lower than that of 1
      oleoyl-LPA. This activation was enantioselective, with the (2S)-enantiomer
      showing 1000-fold more activity than the (2R)-enantiomer. Similar results were
      found for calcium release in HT-29 and OVCAR8 cells. Analogue 15 was also more
      effective than 1-oleoyl-LPA in activating MAPK and AKT in cells expressing high
      levels of LPA(3). The alpha-fluoromethylene phosphonate moiety greatly increased
      the half-life of 15 in cell culture. Thus, alpha-fluoromethylene LPA analogues
      are unique new phosphatase-resistant ligands that provide enantiospecific and
      receptor-specific biological readouts.

PMID- 15857138
TI  - N-terminal fatty acylated His-dPhe-Arg-Trp-NH(2) tetrapeptides: influence of
      fatty acid chain length on potency and selectivity at the mouse melanocortin
      receptors and human melanocytes.
AB  - The melanocortin system is involved in the regulation of a diverse number of
      physiologically important pathways including pigmentation, feeding behavior,
      weight and energy homeostasis, inflammation, and sexual function. All the
      endogenous melanocortin agonist ligands possess the conserved His-Phe-Arg-Trp
      tetrapeptide sequence that is postulated to be important for melanocortin
      receptor molecular recognition and stimulation. Previous studies by our
      laboratory resulted in the discovery that increasing alkyl chain length at the N
      terminal "capping" region of the His-dPhe-Arg-Trp-NH(2) tetrapeptide resulted in
      a 100-fold increased melanocortin receptor agonist potency. This study was
      undertaken to systematically evaluate the pharmacological effects of increasing N
      capping alkyl chain length of the CH(3)(CH(2))(n)CO-His-dPhe-Arg-Trp-NH(2) (n = 6
      16) tetrapeptide template. Twelve analogues were synthesized and
      pharmacologically characterized at the mouse melanocortin receptors MC1R and MC3R
      MC5R and human melanocytes known to express the MC1R. These peptides demonstrated
      melanocortin receptor selectivity profiles different from those of previously
      published tetrapeptides. The most notable results of enhanced ligand potency (20-
      to 200-fold) and receptor selectivity were observed at the MC1R. Tetrapeptides
      that possessed greater than nine alkyl groups were superior to alpha-MSH in terms
      of the stimulation of human melanocyte tyrosinase activity. Additionally, the n
      pentadecanoyl derivative had a residual effect on tyrosinase activity that
      existed for at least 4 days after the peptide was removed from the human
      melanocyte culture medium. These data demonstrate the utility, potency, and
      residual effect of melanocortin tetrapeptides by adding N-terminal fatty acid
      moieties.

PMID- 15857139
TI  - Synthesis and pharmacology of 6-substituted benztropines: discovery of novel
      dopamine uptake inhibitors possessing low binding affinity to the dopamine
      transporter.
AB  - A series of 6alpha- and 6beta-substituted benztropines were synthesized. A marked
      enantioselectivity was observed for the 6beta-methoxylated benztropines, the (1R)
      isomers being more potent than the corresponding (1S) compounds. The racemic
      6alpha-methoxy-3-(4',4' '-difluorodiphenylmethoxy)tropane (5 g) was the most
      potent compound. It has been found that modifications at the 6-position of
      benztropine might reduce the DAT binding affinity, maintaining otherwise a
      significant dopamine uptake inhibitory activity. A reinvestigation of the
      absolute configuration of 6beta-methoxytropinone proved the 6R configuration for
      the (+)-enantiomer.

PMID- 15857140
TI  - Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis and
      biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides.
AB  - Chemical manipulations performed on aroyl-pyrrolyl-hydroxyamides (APHAs) led to
      (aryloxopropenyl)pyrrolyl hydroxamates 2a-w, and their inhibition against maize
      HDACs and their class I or class II HDAC selectivity were determined. In
      particular, from these studies some benzene meta-substituted compounds emerged as
      highly class II (IIa)-selective HDAC inhibitors, the most selective being the 3
      chloro- and 3-fluoro-substituted compounds 2c (SI = 71.4) and2f (SI = 176.4). The
      replacement of benzene with a 1-naphthyl ring afforded 2s, highly active against
      the class II homologue HD1-A (IC(50) = 10 nM) but less class II-selective than
      2c,f. When tested against human HDAC1 and HDAC4, 2f showed no inhibitory activity
      against HDAC1 but was able to inhibit HDAC4. Moreover, in human U937 acute
      myeloid leukaemia cells 2f did not produce any effect on apoptosis, granulocytic
      differentiation, and the cell cycle, whereas 2s (that retain class I HDAC
      inhibitory activity) was 2-fold less potent than SAHA used as reference.

PMID- 15857141
TI  - Symmetrical bis-quinolinium compounds: new human choline kinase inhibitors with
      antiproliferative activity against the HT-29 cell line.
AB  - Studies have been aimed at the establishment of structure-activity relationships
      that define choline kinase inhibitory and antiproliferative activities of 40
      bisquinolinium compounds. These derivatives have electron-releasing groups at
      position 4 of the quinolinium ring. It is found that the enzymatic inhibition is
      closely related to the size of the linker, the 3,3'-biphenyl moiety being the
      most suitable. On the other hand, the antiproliferative activity against the HT
      29 cancer cell line is less influenced by the linker type and by substituent
      R(4). The corresponding QSAR equation was obtained for the whole set of compounds
      for the antiproliferative activity, the electronic parameter sigma(R) of R(4),
      the molar refractivity of R(8), and the lipophilic parameters clog P and
      pi(linker). The most potent antiproliferative agent so far described is 40 for
      which an IC(50) = 0.45 microM was predicted by the QSAR equation, while its
      experimental value is IC(50) = 0.20 microM.

PMID- 15857142
TI  - Platinum(II) complexes with antitumoral/antiviral aromatic heterocycles: effect
      of glutathione upon in vitro cell growth inhibition.
AB  - The compounds [Pt(Me(2)phen)(acy)(2)](NO(3))(2) (1),
      [Pt(Me(2)phen)(pen)(2)](NO(3))(2), [Pt(phen)(acy)(2)](NO(3))(2) (2), and
      [Pt(phen)(pen)(2)](NO(3))(2), containing the bidentate 1,10-phenanthroline (phen)
      or 2,9-dimethyl-1,10-phenanthroline (Me(2)phen, neocuproine) and the antiviral
      agents acyclovir (acy) or penciclovir (pen), show different in vitro toxicity,
      the Me(2)phen complexes being appreciably more toxic than the phen complexes. To
      explain the different behavior, we investigated the reaction of complexes 1 and 2
      with glutathione (gamma-glutamylcysteinylglycine, GSH), a peptide believed to
      play an important role in driving the cellular effects of platinum drugs. The
      reaction led to different products, the phen complexes forming a stable binuclear
      mu-thiol-bridged species still containing the phenanthroline and the Me(2)phen
      complexes releasing the neocuproine ligand and forming an insoluble material. In
      vitro tests confirmed that the greater cell toxicity of complex 1 is due to the
      displacement of the neocuproine ligand by GSH. The results highlight the great
      dependence of the glutathione reactivity upon relatively small changes in the
      platinum coordination sphere.

PMID- 15857143
TI  - Synthesis and biological evaluation of 14-alkoxymorphinans. 22.(1) Influence of
      the 14-alkoxy group and the substitution in position 5 in 14-alkoxymorphinan-6
      ones on in vitro and in vivo activities.
AB  - Novel 14-alkoxy-substituted (e.g. allyloxy, benzyloxy, naphthylmethoxy) morphinan
      6-one derivatives were synthesized and biologically evaluated. Compounds 6-9 and
      11 displayed affinities in the subnanomolar range to mu opioid receptors which
      were comparable to 14-O-methyloxymorphone (1) and 14-methoxymetopon (3), and
      higher than oxymorphone (2). Opioid binding affinity was sensitive to the
      character and length of the substituent in position 14. In smooth muscle
      preparations they behaved as potent agonists. Antinociceptive potencies of
      compounds 6-11 in the hot-plate test after sc administration in mice were
      considerably greater than the potency of morphine. In the colonic propulsion
      test, the most potent analgesic compound 7 showed negligible constipating
      activity at the analgesic dose. These findings provide further evidence that the
      nature of the substituent at position 14 has a major impact on the abilities of
      morphinans to interact with opioid receptors. Introduction of a 5-methyl group
      has no significant effect on in vitro biological activities, but resulted in
      decreased antinociceptive potency.

PMID- 15857144
TI  - Design of benzophenone-containing photoactivatable linear vasopressin
      antagonists: pharmacological and photoreactive properties.
AB  - We designed and synthesized new photoactivatable linear vasopressin analogues
      containing benzophenone photophores. All compounds were monitored and purified
      using RP-HPLC and characterized by mass spectrometry. Affinity and selectivity
      were determined in CHO cells expressing either human V(1a), V(1b) or V(2)
      receptor subtypes. Within the series, compounds 6 (PhCH(2)CO-lBpa-Phe-Gln-Asn-Arg
      Pro-Arg-Tyr(3I)-NH(2)) and 9 (PhCH(2)CO-dBpa-Phe-Gln-Asn-Arg-Pro-Arg-Tyr(3I)
      NH(2)), containing a benzoylphenylalanine residue (Bpa), were selected and their
      antagonistic properties determined (K(inact) = 1.87 and 0.35 nM, respectively).
      The dissociation constant of the most potent candidate (compound 9) was further
      calculated from saturation experiments using the (125)I derivative (K(d) = 0.07
      +/- 0.01 nM). Photolabeling experiments using radioactive compound 9 as a probe
      were specific and UV-dependent and allowed the identification of two bands at
      molecular masses around 85-90 kDa and 46 kDa, respectively, as previously
      described by Phalipou et al., using two photoreactive linear azidopeptide
      antagonists. The results suggest therefore that compound 9 is a potent new tool
      for the accurate mapping of the human V(1a) receptor antagonist binding site.

PMID- 15857145
TI  - Adenosine kinase inhibitors. 4. 6,8-Disubstituted purine nucleoside derivatives.
      Synthesis, conformation, and enzyme inhibition.
AB  - 6,8-Disubstituted purine nucleosides were synthesized and evaluated as adenosine
      kinase inhibitors (AKIs). A method was developed to selectively substitute
      arylamines for halogens at C6 and C8 which utilizes alkali salts of arylamino
      anions. Regioselectivity was found to be counterion dependent. Potassium and
      sodium salts add selectively to C6 of 6-chloro-8-iodo-9-(2,3,5-tris-O-tert
      butyldimethylsilyl-beta-d-ribofuranosyl)purine (7a) while lithium salts add to C6
      and C8 positions. Differential 6,8-bisarylamin-N,N'-diylpurine nucleosides such
      as 8-anilin-N-yl-6-indolin-N-yl-9-(beta-d-ribofuranosyl)purine (10b) can be
      prepared by employing stepwise reactions of potassium and then lithium salts of
      different arylamino anions followed by fluoride ion-induced desilylation. Other
      C8-substituted compounds were prepared by way of either C8 lithiation chemistry
      or palladium cross-coupling reactions. Several of these compounds were potent
      AKIs (e.g. 10b, AK IC(50) = 0.019 microM) and are more potent than the previous
      best purine-based AKI 5'-deoxy-5'-aminoadenosine (AK IC(50) = 0.170 microM). AK
      inhibitory potency was greatest for those compounds with (1)H NMR evidence of a
      predominant anti glycosyl bond conformation, whereas most analogues adopt a syn
      conformation because of steric repulsions between the C8 substituent and the
      ribose group. The inhibitors are proposed to bind in the anti conformation with
      the hydrophobic C6 and C8 substituents contributing to AK affinity in a manner
      similar to the C4 and C5 aryl substituents of the potent diaryltubercidin
      nucleoside inhibitor series.

PMID- 15857146
TI  - C-5-disubstituted barbiturates as potential molecular probes for noninvasive
      matrix metalloproteinase imaging.
AB  - Studies have demonstrated a positive correlation between inflammation,
      metastasis, or atherosclerosis and the unbalanced or culminated expression of
      matrix metalloproteinases (MMPs). The molecular imaging of locally upregulated
      MMP activity in vivo is a clinical challenge. Actually, radioligands based on
      nonpeptidyl MMP inhibitors (MMPIs) are currently in development as putative
      radiopharmaceutical agents for the noninvasive in vivo assessment of activated
      MMPs. Nonpeptidyl MMPIs bind to the zinc active site of the activated enzyme via
      mono- (e.g. carboxylate) or bidentate (e.g. hydroxamate) complexation thereby
      exhibiting a broad-spectrum MMP binding potency. Thus, these mentioned
      endopeptidase inhibitors should be useable lead compounds for the redevelopment
      as diagnostic MMPI radiotracers. Recently, the non-hydroxamate C-5-disubstituted
      pyrimidine-2,4,6-triones were disclosed as subgroup-selective MMP inhibitors. We
      here describe a set of fine-tuned barbiturates as a new class of MMPI
      radiotracers for the noninvasive in vivo visualization of activated MMPs using
      scintigraphic techniques such as SPECT or PET.

PMID- 15857147
TI  - Antitumor effects of two novel naturally occurring terpene quinones isolated from
      the Mediterranean ascidian Aplidium conicum.
AB  - The ascidian Aplidium conicum collected along Sardinia coasts (Italy) contained
      two novel prenylated benzoquinones, designated thiaplidiaquinone A (1) and
      thiaplidiaquinone B (2). These compounds showed an unprecedented tetracyclic
      structure. We have studied the pro-apototic mechanisms of both prenylated
      benzoquinones in the Jurkat cell line that is derived from a human T lymphoma,
      and we show that both compounds induce a strong production of intracellular
      reactive oxygen species (ROS) in this cell line. Moreover, kinetic experiments,
      comparing the timing of ROS induction with the collapse of the mitochondria
      potential (DeltaPsi(m)), clearly showed that ROS preceded the disruption of the
      mitochondrial potential, and the later one paralleled the appearance of apoptotic
      cells. Thus, thiaplidiaquinones A and B can enter into the cells and induce cell
      death by apoptosis.

PMID- 15857148
TI  - Synthesis and in vitro and in vivo antitumor activity of 2-phenylpyrroloquinolin
      4-ones.
AB  - In our search for potential new anticancer drugs, we designed and synthesized a
      series of tricyclic compounds containing the antimitotic 2-phenylazaflavone
      chromophore fused to a pyrrole ring in a pyrroloquinoline structure. Compounds 8,
      18, 19, 22, 23, 25 and 26, when tested against a panel of fourteen human tumor
      cell lines, showed poor in vitro cytotoxic activity, whereas 20, 21 and 24 showed
      significant activity (IC(50) 0.7 to 50 microM). Steroid hormone-sensitive ovary,
      liver, breast and adrenal gland adenocarcinoma cell lines displayed the highest
      sensitivity (IC(50) 0.7 to 8 microM). Compound 24 blocked cells in the G(2)/M
      phase of the cell cycle and induced a significant increase in apoptotis.
      Compounds 20, 21 and 24 proved to alter microtubule assembly and stability,
      displaying a cytoplasmic microtubule network similar to that caused by
      Vincristine. In vivo, administration of compound 24 to Balb/c mice inhibited the
      growth of a syngenic hepatocellular carcinoma.

PMID- 15857150
TI  - Computational strategies in discovering novel non-nucleoside inhibitors of HIV-1
      RT.
AB  - A three-dimensional common feature pharmacophore model was developed using the X
      ray structure of RT/non-nucleoside inhibitor (NNRTI) complexes. Starting from the
      pharmacophore hypothesis and the structure of the lead compound TBZ, new NNRTIs
      were designed and synthesized, having the benzimidazol-2-one system as a
      scaffold. Docking experiments showed that these molecules docked in a position
      and orientation similar to that of known inhibitors. Biological testing confirmed
      that our strategy was successful in searching for new leads as NNRTIs.

PMID- 15857149
TI  - 1,5-Diarylpyrrole-3-acetic acids and esters as novel classes of potent and highly
      selective cyclooxygenase-2 inhibitors.
AB  - A small set of substituted 1,5-diarylpyrrole-3-acetic and -glyoxylic acid
      derivatives have been synthesized, and their cyclooxygenase (COX-1 and COX-2)
      inhibiting properties have been evaluated. Some compounds proved to be highly
      selective COX-2 inhibitors, and their affinity data have been rationalized
      through docking simulations in terms of interactions with a crystallographic
      model of the COX-2 binding site.

PMID- 15857151
TI  - Convergent synthesis and pharmacology of substituted tetrazolyl-2-amino-3-(3
      hydroxy-5-methyl-4-isoxazolyl)propionic acid analogues.
AB  - The synthesis and pharmacological characterization of 1- and 2-alkyltetrazolyl
      analogues of (RS)-2-amino-3-[3-hydroxy-5-(2-methyl-2H-5-tetrazolyl)-4
      isoxazolyl]propionic acid (2-Me-Tet-AMPA), a highly potent and selective agonist
      at AMPA receptors, are presented. A shorter and more convergent synthetic route
      than previously described, employing a new method for introducing the amino acid
      moiety, was developed for these derivatives. The 2-substituted isomers were
      selective agonists, and their activity correlated inversely with the size of the
      substituent. Structural explanations of the structure-activity relationship are
      provided.

PMID- 15857152
TI  - Synthesis and antibacterial activity of the 4-quinolone-3-carboxylic acid
      derivatives having a trifluoromethyl group as a novel N-1 substituent.
AB  - Novel 1-trifluoromethyl-4-quinolone derivatives (8a,b) were synthesized, and the
      antibacterial activity of each was evaluated. An oxidative desulfurization
      fluorination reaction was employed to introduce a trifluoromethyl group at the N
      1 position as a key step. Among the derivatives, 8a was found to exhibit
      antibacterial activity comparable to that of norfloxacin (1) against
      Staphylococcus aureus Smith, Streptococcus pneumoniae IID1210, and Escherichia
      coli NIHJ JC-2.

PMID- 15857153
TI  - Output-mode transitions are controlled by prolonged inactivation of sodium
      channels in pyramidal neurons of subiculum.
AB  - Transitions between different behavioral states, such as sleep or wakefulness,
      quiescence or attentiveness, occur in part through transitions from action
      potential bursting to single spiking. Cortical activity, for example, is
      determined in large part by the spike output mode from the thalamus, which is
      controlled by the gating of low-voltage-activated calcium channels. In the
      subiculum--the major output of the hippocampus--transitions occur from bursting
      in the delta-frequency band to single spiking in the theta-frequency band. We
      show here that these transitions are influenced strongly by the inactivation
      kinetics of voltage-gated sodium channels. Prolonged inactivation of sodium
      channels is responsible for an activity-dependent switch from bursting to single
      spiking, constituting a novel mechanism through which network dynamics are
      controlled by ion channel gating.

PMID- 15857154
TI  - Antigen-engaged B cells undergo chemotaxis toward the T zone and form motile
      conjugates with helper T cells.
AB  - Interactions between B and T cells are essential for most antibody responses, but
      the dynamics of these interactions are poorly understood. By two-photon
      microscopy of intact lymph nodes, we show that upon exposure to antigen, B cells
      migrate with directional preference toward the B-zone-T-zone boundary in a CCR7
      dependent manner, through a region that exhibits a CCR7-ligand gradient.
      Initially the B cells show reduced motility, but after 1 d, motility is increased
      to approximately 9 microm/min. Antigen-engaged B cells pair with antigen-specific
      helper T cells for 10 to more than 60 min, whereas non-antigen-specific
      interactions last less than 10 min. B cell-T cell conjugates are highly dynamic
      and migrate extensively, being led by B cells. B cells occasionally contact more
      than one T cell, whereas T cells are strictly monogamous in their interactions.
      These findings provide evidence of lymphocyte chemotaxis in vivo, and they begin
      to define the spatiotemporal cellular dynamics associated with T cell-dependent
      antibody responses.

PMID- 15857156
TI  - Apolipoprotein AV variants do not affect C-reactive protein levels in Caucasian
      males.
AB  - The important role of APOAV gene variants in determination of plasma triglyceride
      levels has been shown in many population studies. Recently, an influence of APOAV
      T-1131>C polymorphism on C-reactive protein (CRP) in young Korean males has been
      reported. We have therefore analyzed a putative association between T-1131>C,
      Ser19>Trp and Val153>Met APOAV variants (PCR and restriction analysis) and CRP
      concentrations in 1119 Caucasian males, aged between 28 and 67 years (49.2+/-10.8
      years). The frequency of C allele carriers was lower in Caucasians than in
      Koreans (15.5% vs. 46.2%). CRP levels did not differ between T/T homozygotes
      (n=946, 1.61+/-2.05 mg/l) and carriers of the C allele (n=173, 1.67+/-1.95 mg/l).
      Thus, in contrast to Korean males, T-1131>C APOAV variant has no effect on plasma
      concentrations of CRP in a large group of Caucasian males. Other APOAV variants
      (Ser19>Trp and Val153>Met) did not also influence plasma concentrations of CRP.
      APOAV variants are unlikely to be an important genetic determinant of plasma CRP
      concentrations in Caucasian males.

PMID- 15857155
TI  - Oxygenation inhibits the physiological tissue-protecting mechanism and thereby
      exacerbates acute inflammatory lung injury.
AB  - Acute respiratory distress syndrome (ARDS) usually requires symptomatic
      supportive therapy by intubation and mechanical ventilation with the supplemental
      use of high oxygen concentrations. Although oxygen therapy represents a life
      saving measure, the recent discovery of a critical tissue-protecting mechanism
      predicts that administration of oxygen to ARDS patients with uncontrolled
      pulmonary inflammation also may have dangerous side effects. Oxygenation may
      weaken the local tissue hypoxia-driven and adenosine A2A receptor (A2AR)-mediated
      anti-inflammatory mechanism and thereby further exacerbate lung injury. Here we
      report experiments with wild-type and adenosine A2AR-deficient mice that confirm
      the predicted effects of oxygen. These results also suggest the possibility of
      iatrogenic exacerbation of acute lung injury upon oxygen administration due to
      the oxygenation-associated elimination of A2AR-mediated lung tissue-protecting
      pathway. We show that this potential complication of clinically widely used
      oxygenation procedures could be completely prevented by intratracheal injection
      of a selective A2AR agonist to compensate for the oxygenation-related loss of the
      lung tissue-protecting endogenous adenosine. The identification of a major
      iatrogenic complication of oxygen therapy in conditions of acute lung
      inflammation attracts attention to the need for clinical and epidemiological
      studies of ARDS patients who require oxygen therapy. It is proposed that oxygen
      therapy in patients with ARDS and other causes of lung inflammation should be
      combined with anti-inflammatory measures, e.g., with inhalative application of
      A2AR agonists. The reported observations may also answer the long-standing
      question as to why the lungs are the most susceptible to inflammatory injury and
      why lung failure usually precedes multiple organ failure.

PMID- 15857157
TI  - Tissue specific and variable collagen proliferation in Swiss albino mice treated
      with clenbuterol.
AB  - Chronic administration of clenbuterol, a beta-adrenoceptor agonist (2 mg/kg body
      weight/day for 30 days) to mice resulted in an increased body mass. Measurement
      of dry tissue mass suggested a protein anabolic effect in the gastrocnemius and
      heart. Quantitative estimation of collagen content, a non-contractile element as
      calculated from hydroxyproline assay revealed its proliferation in the
      gastrocnemius, cardiac ventricle, intestine and to some extent also in the
      kidney. Clenbuterol did not induce collagen proliferation in non-muscle tissues
      such as the lungs and liver. Histopathological examination of sections from
      treated ventricles showed an extensive collagen infiltration in the
      subendocardium and at myonecrosis sites.

PMID- 15857158
TI  - Dopamine mimics the cardioprotective effect of ischemic preconditioning via
      activation of alpha1-adrenoceptors in the isolated rat heart.
AB  - The aim of the present study was to clarify whether pharmacological
      preconditioning with dopamine protects the heart against ischemia and whether
      this effect is mediated through dopaminergic receptors (D1 and D2) or alpha1
      adrenoceptors. Isolated perfused rat hearts were either non-preconditioned,
      preconditioned with 5 min ischemia, or treated for 5 min with dopamine (1, 5 or
      10 microM) before being subjected to 45 min of sustained ischemia followed by 60
      min reperfusion. Postischemic functional recovery and infarct size were used as
      indices of the effects of ischemia. Treatment with the lower concentration of
      dopamine (1 microM), did not provide any protection to the ischemic myocardium.
      On the other hand, treatment with 5 microM dopamine resulted in significantly
      improved functional recovery, whereas administration of dopamine (10 microM)
      resulted in significantly improved functional recovery as well as reduction of
      infarct size. Pretreatment with the mixed D1/D2 dopaminergic receptor antagonist
      haloperidol or the beta-adrenoceptor selective antagonist propranolol did not
      attenuate the protective effect of pharmacological preconditioning with 10 microM
      dopamine with respect to both functional recovery and infarct size reduction. On
      the other hand, the cardioprotective effect of dopamine was blocked when the
      alpha1-adrenoceptor selective antagonist, prazosin, was administered. In
      conclusion, pharmacological preconditioning with dopamine protects the myocardium
      against ischemia and this effect seems to be mediated through activation of
      alpha1-adrenoceptors.

PMID- 15857159
TI  - Relationship among urinary albumin excretion rate, lipoprotein lipase PvuII
      polymorphism and plasma fibrinogen in type 2 diabetic patients.
AB  - Plasma fibrinogen level represents a strong cardiovascular risk factor and is
      regulated by an interplay of genetic and environmental factors.
      Hyperfibrinogenemia frequently occurs in cluster with dyslipidemia within the
      frame of insulin resistance syndrome (IRS) and type 2 diabetes mellitus. Genetic
      variants with a pleiotropic effect have been proposed to cause IRS features
      including hyperfibrinogenemia. We studied the influence of polymorphisms in
      lipoprotein lipase (LPL) gene, beta-fibrinogen gene (FIBB) and environmental
      factors on plasma fibrinogen levels in type 2 diabetes patients. 131 type 2
      diabetes patients (mean age 62+/-10 years, 33% male) were genotyped for
      polymorphisms in LPL gene (intron 6 PvuII, intron 8 HindIII) and FIBB gene (
      148C/T, -455G/A) by PCR-RFLP method. Fibrinogen was measured by thrombin
      coagulation method, albuminuria by immunoturbidimetric assay. Polymorphism LPL
      PvuII showed a gene-dose effect on fibrinogen levels, with the highest fibrinogen
      in P-P- homozygotes (p = 0.05, analysis of variance). P-carriers (P-P- and P+P-
      combined) had significantly higher fibrinogen levels compared with P+P+
      homozygotes (3.74+/-1.40 g/l vs 3.06+/-1.20 g/l, p=0.03). Other studied
      polymorphisms were not significantly related to fibrinogen levels. Age- and sex
      adjusted fibrinogenemia correlated significantly with albuminuria (r = 0.48,
      p=0.001), serum uric acid (r = 0.42, p=0.006) and serum creatinine (r = 0.32,
      p=0.04). Multiple stepwise linear regression identified interaction term of LPL
      PvuII and albuminuria as an independent predictor of fibrinogen level, explaining
      18% of fibrinogen variance. Albuminuria thus appears to be the best predictor of
      fibrinogen plasma levels in type 2 diabetic patients. Relationship between
      albuminuria and fibrinogenemia may be modified by the genotype LPL PvuII, which
      also shows a weak association with plasma fibrinogen level in type 2 diabetes
      patients.

PMID- 15857160
TI  - Operant behavior of the rat can be controlled by the configuration of objects in
      an animated scene displayed on a computer screen.
AB  - We developed a novel behavioral task in which rats learn to recognize the
      configuration of objects in an animated scene displayed on a computer screen. The
      scene consisted of a moving bar and a stationary rectangle. Rats deprived of food
      were trained to press a lever for reward in a small chamber located in front of
      the screen. Lever presses were rewarded only when the bar was at the rectangle.
      Rats anticipated the reward by gradually increasing frequency of lever pressing
      as the bar approached the rectangle. Control experiments showed that neither the
      timing nor the discrimination of rewarded and non-rewarded periods as two
      discrete conditions explain behavior of the rat. Because the changes in the scene
      were generated by movement of the object, the presented task could be used for
      studying neural structures involved in spatial behavior of rats using virtual
      reality technology.

PMID- 15857161
TI  - Imbalance between apoptosis and proliferation causes late radiation damage of
      salivary gland in mouse.
AB  - Severe xerostomia is a common late radiation consequence, which occurs after
      irradiation of head and neck malignancies. The aim of the present study was to
      analyze apoptosis and proliferation and their relationship during the late post
      irradiation phase. C57BL/6 mice were locally irradiated in head and neck region
      with a single dose of 7.5 or 15 Gy and their submandibular glands were collected
      at 40 and 90 days after irradiation. To identify apoptotic cells, the TUNEL
      method was employed and immunohistochemistry with proliferating cell nuclear
      antigen (PCNA) was used for detecting proliferation. Histological changes at day
      40 were mild in contrast to day 90 when glands of irradiated mice showed severe
      atrophy, vacuolization and mononuclear infiltration. Acinar cells, granular and
      intercalated duct cells of mice irradiated with 7.5 and 15 Gy expressed higher
      apoptotic index than cells of non-irradiated, control glands at both examined
      time points. At 40 days, a higher proliferation index in granular and
      intercalated duct cells was detected only in group irradiated with 7.5 Gy. At 90
      days, proliferation index for all cell types in both irradiated groups was
      similar to the controls. According to our results, the imbalance between
      apoptosis and proliferation caused by X-irradiation may be the reason for gland
      impairment during the late post-irradiation phase.

PMID- 15857162
TI  - The influence of n-3 polyunsaturated fatty acids and very low calorie diet during
      a short-term weight reducing regimen on weight loss and serum fatty acid
      composition in severely obese women.
AB  - Polyunsaturated fatty acids of n-3 series (n-3 PUFA) were shown to increase basal
      fat oxidation in humans. The aim of the study was to compare the effect of n-3
      PUFA added to a very low calorie diet (VLCD), with VLCD only during three-week
      inpatient weight reduction. Twenty severely obese women were randomly assigned to
      VLCD with n-3 PUFA or with placebo. Fatty acids in serum lipid fractions were
      quantified by gas chromatography. Differences between the groups were determined
      using ANOVA. Higher weight (7.55+/-1.77 vs. 6.07+/-2.16 kg, NS), BMI (2.82+/-0.62
      vs. 2.22+/-0.74, p<0.05) and hip circumference losses (4.8+/-1.81 vs. 2.5+/-2.51
      cm, p<0.05) were found in the n-3 group as compared to the control group.
      Significantly higher increase in beta-hydroxybutyrate was found in the n-3 group
      showing higher ketogenesis and possible higher fatty acid oxidation. The increase
      in beta-hydroxybutyrate significantly correlated with the increase in serum
      phospholipid arachidonic acid (20:4n-6; r = 0.91, p<0.001). In the n-3 group
      significantly higher increase was found in n-3 PUFA (eicosapentaenoic acid, 20:5n
      3, docosahexaenoic acid, 22:6n-3) in triglycerides and phospholipids. The
      significant decrease of palmitoleic acid (16:1n-7) and vaccenic acid (18:1n-7) in
      triglycerides probably reflected lower lipogenesis. A significant negative
      correlation between BMI change and phospholipid docosahexaenoic acid change was
      found (r = -0.595, p<0.008). The results suggest that long chain n-3 PUFA enhance
      weight loss in obese females treated by VLCD. Docosahexaenoate (22:6n-3) seems to
      be the active component.

PMID- 15857163
TI  - The dynamics of gene expression in human lung microvascular endothelial cells
      after stimulation with inflammatory cytokines.
AB  - Vascular endothelium plays an essential role in the pathogenesis of
      vasoocclusion. The changes in the endothelial cell function can be triggered by
      changes in gene expression caused by interaction with cytokines and blood cells.
      Using cDNA arrays, we have recently reported complex patterns of gene expression
      after stimulation of endothelial cells with TNFalpha and IL-1beta. Better
      understanding of the time course of gene expression changes, their concentration
      dependence and reversibility after withdrawal of the offending cytokine is
      essential for successful prevention and therapy of vasoocclusion. Here we present
      a detailed study of the concentration dependence and time course of gene
      expression in endothelial cells after their exposure to TNFalpha and IL-1beta. We
      focus on the adhesion molecules (VCAM-1, ICAM-1, E-selectin) and cytokines (IL-6,
      GCP-2, MCP-1) that are likely to contribute to vasoocclusion. We report
      differences in the time course and intensity of their expression and in their
      response to TNFalpha and IL-1beta stimulation. We demonstrate that expression of
      the studied genes is upregulated by low TNFalpha concentrations that better
      reflect the TNFalpha levels detected in the plasma of patients developing
      vasoocclusion. These results help to understand the changes in the endothelium
      and to design rational prevention and therapy of vasoocclusion.

PMID- 15857164
TI  - Long-term monitoring of the changes in signal-averaged ECG after coronary artery
      occlusion and intracoronary endothelin-1 injection in dogs.
AB  - Myocardium undergoes functional changes in the infarcted region primarily due to
      ischemia. Following myocyte functional alterations of the noninfarcted myocardium
      are caused by remodelling and hypertrophy. We have monitored and compared changes
      in the electrocardiographical (ECG) image after coronary artery occlusion (CAO,
      n=5) and intracoronary endothelin-1 (ET-1, n=3) administration during a 6-month
      period. In 3 dogs, the CAO was repeated 6 months after the first occlusion.
      Signal-averaged ECG (SA ECG) was recorded before the operation and 10 days, 1
      month, 3 months and 6 months after myocardial infarction (MI). The modified
      Wigner distribution was used for spectrotemporal analysis of the SA ECG. Eight
      hour Holter monitoring was performed in each dog before and after experimental
      MI. Spectrotemporal representations of the QRS complex were stabilized after the
      first 1-month period in the group of dogs after CAO. The same results were also
      observed after the repeated CAO. No arrhythmias were recorded 9 days after CAO.
      The spectrotemporal representations of the QRS complex after intracoronary ET-1
      administration were not stabilized during the whole observed period. Very few
      arrhythmic events were recorded by Holter monitoring already 3 days after
      intracoronary ET-1 injection. Experimental MI induced by CAO caused a changed ECG
      image, which was stable from 1 month after MI induction till the end of the
      monitoring. However, the ECG image after ET-1 administration was not stable
      during the whole observed period. No arrhythmic events were recorded in either
      group 3 months postoperatively that could be caused by healthy myocardial status
      before the experimental MI induction. In clinical practice, however, ischemic
      heart disease usually precedes the MI. Arrhythmogenic substrate could thus be a
      consequence of combination of healthy status of the myocardium before MI and MI
      itself.

PMID- 15857165
TI  - Risperidone potentiates the sympathetic and hyperthermic reactions induced by
      orexin A in the rat.
AB  - This experiment tested the effect of risperidone on the sympathetic and
      thermogenic effects induced by orexin A. The firing rates of sympathetic nerves
      to interscapular brown adipose tissue (IBAT), along with IBAT and colon
      temperatures and heart rate were monitored in urethane-anesthetized male Sprague
      Dawley rats before an injection of orexin A (1.5 nmol) into the lateral cerebral
      ventricle and over a period of 2 hours after the injection. The same variables
      were monitored in rats with an intraperitoneal administration of risperidone (50
      mg/kg bw), injected 30 min before the orexin administration. The results show
      that orexin A increases the sympathetic firing rate, IBAT, colonic temperatures
      and heart rate. This increase is enhanced by the injection of risperidone. These
      findings suggest that risperidone elevates the responses due to orexin, probably
      through an involvement of serotoninergic and dopaminergic pathways, which are
      affected by risperidone. Furthermore, we suggested the name "hyperthermine A" as
      additional denomination of "orexin A" by considering the strong influence of this
      neuropeptide on body temperature.

PMID- 15857166
TI  - Erythropoietin decreases cytotoxicity and nitric oxide formation induced by
      inflammatory stimuli in rat oligodendrocytes.
AB  - In the present study, we investigated whether erythropoietin (Epo) has a
      protective effect against cytotoxicity induced by interferon-gamma (IFN-gamma )
      and lipopolysaccharide (LPS) in primary rat oligodendrocyte cultures. The
      possible modulatory effect of erythropoietin on inducible nitric oxide synthase
      (iNOS) mRNA expression and nitrite production were also analyzed. Erythropoietin
      exerted a significant protective effect against IFN-gamma and LPS-induced
      oligodendrocyte injury as determined by lactate dehydrogenase assay. Treatment
      with erythropoietin inhibited the expression of iNOS mRNA and nitrite production
      resulting from proinflammatory stimulation by IFN-gamma and LPS. These results
      suggest that erythropoietin has protective effects against inflammatory
      oligodendrocyte injury in vitro and may play a protective role in neurological
      disorders characterized by oligodendrocyte death, such as multiple sclerosis.

PMID- 15857167
TI  - How short-term transdermal treatment of men with 7-oxo-dehydroepiandrosterone
      influence thyroid function.
AB  - Dehydroepiandrosterone may influence thyroid function. Its metabolite, 7-oxo
      dehydroepiandrosterone, a precursor of immunomodulatory 7-hydroxylated
      metabolites and thermogenic agent, belongs to candidates of steroid replacement
      therapy. The question was addressed whether its application does influence
      laboratory parameters of thyroid function. 7-Oxo-dehydroepiandrosterone in the
      form of emulgel, 25 mg/day, was applied transdermally to 21 healthy men for 8
      consecutive days. Morning blood was collected before the treatment (Day 0, Stage
      1), during treatment (Day 5, Stage 2), on the first day after the last
      administration (Day 9, Stage 3), one week (Day 16, Stage 4), and 9 weeks (Day 72,
      Stage 5) after treatment termination. The levels of thyrotropin, free thyroxine
      and triiodothyronine, dehydroepiandrosterone, its sulfate and its 7
      hydroxyepimers were measured. The changes were evaluated by analysis of variance
      and correlation analysis. During treatment a significant rise of 7beta-hydroxy
      dehydroepiandrosterone was observed, which persisted 1 week after treatment
      termination. No changes were observed in dehydroepiandrosterone and its sulfate.
      Though a slight but significant rise of TSH and of both thyroid hormones occurred
      during treatment, its levels soon returned to the basal values. It was concluded
      that treatment of 7-oxo-dehydroepiandrosterone affects the thyroid parameters
      only temporarily and that it provides a considerable persistent amount of 7beta
      hydroxy-dehydroepiandrosterone.

PMID- 15857168
TI  - Effects of the perfusion flow rate on skeletal muscle energy metabolism and a
      possible role of second messengers in this process.
AB  - The metabolic turnover in the isolated in vitro perfused and superfused rat
      skeletal muscle (musculus gracilis cranialis) was enhanced by increasing the
      medium flow rate under relaxed conditions. In a recent study we have measured the
      tissue concentrations of second messengers: cyclic adenosine 3'5'-monophosphate
      (cAMP), cyclic guanosine 3'5'-monophosphate (cGMP), and D-myo-inositol 1,4,5
      trisphosphate (IP3) under similar experimental conditions to analyze their
      potential role in the described stimulation of metabolic rate by changes of
      perfusion flow rate. The tissue levels of the two second messengers' cAMP and
      cGMP were not significantly changed after increasing the perfusion flow rate and
      they probably have no transduction role in the induced alteration of skeletal
      muscle metabolism. However, the IP3 content was extremely reduced after
      increasing flow rate. This decrease in the tissue concentration of IP3 induced by
      increasing the flow rate indicates the possible role of IP3 in this signal
      transduction, leading to changes in the cellular metabolic pathways.

PMID- 15857169
TI  - Normocapnic high-frequency oscillatory ventilation affects differently
      extrapulmonary and pulmonary forms of acute respiratory distress syndrome in
      adults.
AB  - The recently reported differences between pulmonary and extrapulmonary acute
      respiratory distress syndromes (ARDS(p), ARDS(exp)) are the main reasons of
      scientific discussion on potential differences in the effects of current
      ventilatory strategies. The aim of this study is to assess whether the presence
      of ARDS(p) or ARDS(exp) can differently affect the beneficial effects of high
      frequency oscillatory ventilation (HFOV) upon physiological and clinical
      parameters. Thirty adults fulfilling the ARDS criteria were indicated for HFOV in
      case of failure of conventional ventilation strategy. According to the ARDS type,
      each patient was included either in the group of patients with ARDS(p) or
      ARDS(exp). Six hours after normocapnic HFOV introduction, there was no
      significant increase in PaO2/F(I)O2 in ARDS(p) group (from 129+/-47 to 133+/-50
      Torr), but a significant improvement was found in ARDS(exp) (from 114+/-54 to
      200+/-65 Torr, p<0.01). Despite the insignificant difference in the latest mean
      airway pressure (MAP) on conventional mechanical ventilation (CMV) between both
      groups, initial optimal continuous distension pressure (CDP) for the best
      PaO2/F(I)O2 during HFOV was 2.0+/-0.6 kPa in ARDS(p) and 2.8+/-0.6 kPa in
      ARDS(exp) (p<0.01). HFOV recruits and thus it is more effective in ARDS(exp).
      ARDS(exp) patients require higher CDP levels than ARDS(p) patients. The testing
      period for positive effect of HFOV is recommended not to be longer than 24 hours.

PMID- 15857170
TI  - Epitope mapping of recombinant hepatitis B surface antigen by murine monoclonal
      antibodies.
AB  - Hepatitis B surface antigen (HBsAg) induces a potent protective antibody response
      in immunized healthy individuals. The antibody response in humans is largely
      directed to a restricted conformational immunodominant region of HBsAg,
      identified as "a" determinant. Our aim was generation and characterization of
      murine monoclonal antibodies (MAbs) against recombinant HBsAg and their use for
      epitope mapping of the antigen. Hybridoma cells were established from Balb/c mice
      immunized with recombinant HBsAg of the "adw" subtype and cloned by limiting
      dilution. Specificity of MAbs was studied by indirect ELISA and immunoblotting.
      Topology of the epitopes was analyzed by competitive and inhibition ELISA. Eight
      hybridoma clones producing MAbs specific for the immunogen were established. Five
      of the MAbs recognized overlapping conformational epitopes, whereas the remaining
      three MAbs were found to identify linear epitopes. Cross-inhibition studies
      suggest recognition of mutually exclusive epitopes by these MAbs. Our data
      suggest that, similar to the human system, the mouse antibody response is largely
      directed to restricted conformational overlapping epitopes of HBsAg.

PMID- 15857171
TI  - Characterization of human tissue factor (TF)-specific monoclonal antibodies
      prepared using a rapid immunization protocol.
AB  - Tissue factor (TF) plays an important, physiological role in hemostasis. Recent
      studies have demonstrated the over-expression of TF in a number of solid tumor
      types and its pathological roles in angiogenesis and tumor metastasis. In this
      study, we report the development and characterization of a panel of murine MAbs
      that are specific for human TF, but do not inhibit TF-mediated blood coagulation.
      By using a modified repetitive immunizations at multiple sites (RIMMS) protocol
      in conjunction with an efficient hybridoma cloning procedure, anti-TF MAbs were
      generated within a relatively short time frame of 5-6 weeks. Following primary
      screening by ELISA, the binding of the MAbs to the native form of human TF was
      demonstrated in flow cytometry using a stable cell line expressing human TF.
      Several of these TF-specific MAbs did not inhibit blood coagulation in a blood
      coagulation assay and bound with high affinity (0.5-2 nM) to human TF in BIAcore
      analyses. Importantly, this study represents an independent evaluation of the
      RIMMS strategy for MAb generation and demonstrates that class-switched, high
      affinity MAbs can be generated rapidly and reliably using RIMMS.

PMID- 15857172
TI  - Monoclonal antibodies to esophageal cancer-related gene2 protein.
AB  - Esophageal cancer related gene2 (ECRG2) acts as a bi-functional gene associated
      with regulation of cell growth and death, and plays an important role in
      carcinogenesis of esophageal cancer. RT-PCR and Northern blot data showed that
      ECRG2 was expressed in normal esophagus, liver, colon, and lung tissues, but lost
      or greatly down-regulated in the adjacent and cancerous tissues, especially in
      esophageal cancer. However, studies of protein have been hampered by the lack of
      a sensitive and specific antibody. Here, we generated anti-ECRG2 monoclonal
      antibodies (MAbs) by using c-terminal of ECRG2 peptide as immunogen. Antibodies
      8C9c53, 5E3c9, and 3C5c76, are suitable for detecting the ECRG2 on ELISA and
      Western blot assays, and 1E4c2 and 4B6c41 are suitable for immunofluorescence
      microscopy. The study also provides novel data about ECRG2 protein expression in
      the cytoplasm and the possibility of post-translation modification in mammalian
      cells. Based on these findings, it may be expected that anti-ECRG2 monoclonal
      antibodies will be valuable tools for research and diagnosis.

PMID- 15857173
TI  - Production and characterization of monoclonal antibodies to mesenchymal stem
      cells derived from human bone marrow.
AB  - The bone marrow (BM) serves as a reservoir for different classes of stem cells.
      In addition to haematopoietic stem cells, bone marrow contains a population of
      mesenchymal stem cells (MSCs). These cells have a multilineage differentiation
      capacity and are able to generate progenitors with restricted developmental
      potential, which include fibroblasts, osteoblasts, adipocytes, and chondrocytes.
      Characteristic markers have been reported for expanded MSCs, but none of these
      markers are specific for MSCs. Thus, the objective of this study was to produce
      monoclonal antibodies against MSCs. MSCs derived from human bone marrow were
      cultured, expanded, and immunized into mice, and spleen cells subsequently
      harvested were used to generate hybridoma cell lines secreting antibodies against
      MSCs. Hybridoma culture supernatants were screened for antibodies against MSCs by
      enzyme-linked immunosorbent assay (ELISA), and 33 positive clones were then
      screened against cell suspensions of MSCs by immunofluorescence staining and flow
      cytometry. Ten clones were positive in immunofluorescence staining. Among these,
      three hybridoma cell lines, namely, YS08, YS14, and YS18 were found to be
      reactive with MSC by flow cytometry, but non-reactive with human tumor cell lines
      and hematopoietic stem cells. YS08 and YS14 showed specific bands in Western
      blotting. In conclusion, we developed three monoclonal antibodies, YS08, YS14,
      and YS18, that recognize human MSC cell surface antigen.

PMID- 15857174
TI  - Generation and characterization of monoclonal antibodies to human PCTAIRE 3.
AB  - Monoclonal antibodies specific for the unique N-terminal domain of the PCTAIRE 3
      protein kinase have been produced and characterized. The specificity of these
      antibodies has been assessed by ELISA, Western blot, and immunoflorescence
      techniques. These reagents are specific for recombinant PCTAIRE 3 of human origin
      and do not cross-react with PCTAIRE 1 or PCTAIRE 2, despite the high homology
      between members of the PCTAIRE subfamily of cdc2-like kinases. Immunoblotting of
      transfected cells reveals that all of the antibodies recognize both isoforms of
      the PCTAIRE 3 kinase. Epitope mapping reveals three distinct classes of PCTAIRE 3
      antibodies that recognize different sites within an immunodominant region of the
      N-terminal domain of the protein. The creation of highly specific PCTAIRE 3
      monoclonal reagents will be useful for assessing the native distribution and
      function of this protein.

PMID- 15857175
TI  - Preparation and characterization of a monoclonal antibody specific to histone
      acetyltransferase from Plasmodium falciparum.
AB  - We have obtained a specific monoclonal antibody (MAb) against the Plasmodium
      falciparum histone acetyl transferase (PfGcn5), a transcriptional factor that
      possesses HAT activity directed to the amino terminal of histone H3. To prepare
      this antibody, a 968-base pair (bp) DNA fragment of PfGcn5 gene corresponding to
      C-terminal domain was obtained by RT-PCR and cloned into prokaryotic expression
      vector pGEX-4T3. MAb against PfGcn5 was obtained with hybridoma technique and
      ELISA screening using either purified GSTPfGcn5 protein or purified GST protein
      alone as a control. One MAb, named Pf.r2, was able to identify the PfGcn5 protein
      in nuclear extract from P. falciparum and immunofluorescence assays. This MAb
      will be a helpful tool to perform a variety of assays to identify the other
      components of PfGcn5 complexes.

PMID- 15857176
TI  - Chicken anti-protein L for the detection of small amounts of protein L in the
      presence of IgG.
AB  - Protein L is a cell surface protein, expressed by Peptostreptoccocus magnus,
      which binds to the variable light chains of immunoglobulins without interfering
      with antigen binding. It can be used for purification of mammalian antibodies of
      all classes in contrast to the Ig-binding proteins protein A and protein G.
      Detection of protein L leakage into antibody preparations is important, since
      protein L could interfere in immunological assays and cause adverse reactions in
      vivo. Here we have developed a sandwich ELISA for detection of protein L in the
      presence or absence of mouse IgG utilizing specific chicken IgY antibodies.
      Protein L does not react with chicken IgY light chains, and it is therefore
      possible to make an antigen-specific assay. The assay can be used to detect
      protein L at a concentration of 0.3 ng/mL in the presence of IgG.

PMID- 15857177
TI  - Generation of a mouse monoclonal antibody against chicken interleukin-6.
AB  - A monoclonal antibody (MAb) specific for chicken interleukin-6 (chIL-6) was
      generated by using Balb/c mice immunized with recombinant chIL-6 (rchIL-6). On
      Western blot analysis, the MAb, designated E3, reacted with rchIL-6 but not with
      recombinant murine IL-6 (rmIL-6). The MAb E3 also reacted with supernatant of the
      chicken macrophage-like cell line HD11 stimulated with lipopolysaccaride. The
      rchIL-6-induced phosphorylation of STAT3 in a chicken hybridoma cell line was
      inhibited by addition of MAb E3 in a dose-dependent manner. These results
      indicate that the MAb E3 specific for chIL-6 is useful for detection and
      functional analysis of chIL-6.

PMID- 15857179
TI  - Homogeneous amplification nucleobase quenching assay to detect the E474Q LCHAD
      deficiency mutation.
AB  - Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is a rare and
      potentially fatal autosomal recessive disorder of fatty acid metabolism. Early
      institution of dietary therapy is essential and places a premium on rapid
      diagnosis. Pregnancy with an LCHAD-deficient fetus is often complicated in the
      third trimester by liver disease, particularly acute fatty liver of pregnancy.
      All cases of isolated LCHAD deficiency have at least one copy of the E474Q
      mutation in the gene encoding the alpha-subunit of the mitochondrial
      trifunctional protein. Previously published methods for detecting this mutation
      are based upon allele-specific restriction enzyme digestion of a DNA fragment
      generated by PCR, followed by gel electrophoresis to resolve the products. We
      have developed a faster and less expensive assay for the E474Q mutation using PCR
      followed directly by differential melting of a fluorescently labeled
      oligodeoxyribonucleotide probe, using nucleobase quenching to detect probe
      hybridization.

PMID- 15857180
TI  - Microarray-based detection of mannose-binding lectin 2 (MBL2) polymorphisms in a
      routine clinical setting.
AB  - The assessment of allelic variants in the human mannose-binding lectin 2 (MBL2)
      gene is of great clinical importance in newborns or immune-suppressed patients at
      high risk for a variety of infections. Here, we present a study on the genotyping
      accuracy of a DNA microarray-based on-chip PCR method suited for the detection of
      five different polymorphisms in the MBL2 gene. We tested 153 genomic DNA samples,
      prepared from archival blood spots on Guthrie cards, for the presence of allelic
      variants in the human MBL2 gene by the on-chip PCR method and compared the
      obtained results of three variants to standard DNA capillary sequencing. The
      genotyping power of the described assay was readily comparable to DNA sequencing
      (453/459 correct genotype calls in 153 DNA samples; 98.7% accuracy), mainly due
      to intrinsic technical benefits of microarrays such as high number of test
      replicates and automated data analysis. This study demonstrates, for the first
      time, the accuracy and reliability of a microarray-based on-chip PCR genotyping
      assay for measuring allelic variants in a routine clinical setting.

PMID- 15857181
TI  - Detection of rearrangements in the NF2 gene using semi-quantitative multiplex
      fluorescent PCR.
AB  - Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder that predisposes
      to the development of bilateral vestibular schwannomas (sometimes associated with
      schwannomas at other locations), meningiomas, and ependymomas. Point mutations
      that inactivate the NF2 tumor suppressor gene, located in 22q12, have been found
      in 45-85% of NF2 patients; in addition, large genomic deletions can be found. To
      evaluate the presence of genomic NF2 rearrangements, we have developed a
      fluorescent semiquantitative multiplex PCR method. Briefly, short fragments
      corresponding to the 17 exons, the promoter region, and the 3' end of the NF2
      gene were co-amplified by PCR using dye primers. An additional fragment,
      corresponding to another gene used as an internal control, was systematically
      amplified in each multiplex PCR. Initially, we validated the method by using
      monosomic 22q and trisomic 22 samples. The fluorescent multiplex PCR method was
      then used to analyze 21 NF2 individuals in which single-strand conformational
      polymorphism (SSCP) analysis and/or direct sequencing had revealed no NF2 point
      mutations; we were able to detect two deletions and one duplication in NF2 in 3
      patients. In conclusion, the method we developed could easily be applied in
      detecting NF2 deletions and duplications. Discovering genomic duplications is
      invaluable because they are probably the most difficult molecular alterations to
      detect with conventional methods and, as a consequence, might be an
      underestimated cause of NF2.

PMID- 15857182
TI  - The 35delG mutation in the connexin 26 gene (GJB2) associated with congenital
      deafness: European carrier frequencies and evidence for its origin in ancient
      Greece.
AB  - The 35delG mutation in the connexin 26 gene (GJB2) at the DFNB1 locus represents
      the most common mutation in Caucasian patients with genetic sensorineural
      deafness. This new meta-analysis concerns published carrier frequencies of the
      35delG mutation in 27 populations for 6,628 unrelated individuals in Europe and
      in the Middle East; the mean carrier frequency of the mutation is 1.9%. Compared
      on a regional basis, the most elevated carrier frequency value is of 1 individual
      carrier in 31 in southern Europe. It is probable that the 35delG mutation
      originated in ancient Greece and was subsequently propagated in other
      Mediterranean countries (especially in Italy) during recent historical times.

PMID- 15857183
TI  - Phenotypic heterogeneity in patients with Gaucher disease and the N370S/V394L
      genotype.
AB  - Correlation between genotype and phenotype in Gaucher disease is limited. It is
      known that the most common mutation N370S is protective of neurological
      involvement, but for the V394L mutation, described as the fifth most common among
      Ashkenazi Jews, little data are available. This study reports all known patients
      from a large referral clinic and from the international registry with Gaucher
      disease who are documented to have the N370S/V394L genotype. Of 476 patients in
      the Gaucher Clinic, 7 patients (2.0%) had the N370S/V394L genotype; of 2,836
      patients in the registry, there were 14 patients (0.8%) with this genotype. There
      was an overlap of 3 patients, making a total of 18 patients, reflecting the
      rarity of this genotype among the studied cohorts. Most of these patients had
      mild disease; only 8 patients required specific enzyme therapy, none was
      splenectomized. Only 3 patients had skeletal involvement, but other baseline
      parameters were very diverse. Although genotype-phenotype correlation in this
      case may be difficult, because the V394L mutation when seen in a compound
      heterozygote with a null allele results in neuronopathic disease, one cannot
      conclude that this mutation is protective of neuronopathic disease and hence this
      is important for counseling of at-risk populations.

PMID- 15857184
TI  - Facioscapulohumeral muscular dystrophy type 1A in northwestern Tuscany: a
      molecular genetics-based epidemiological and genotype-phenotype study.
AB  - Facioscapulohumeral muscular dystrophy type 1A (FSHD1A) is an autosomal dominant
      inherited disorder characterized by early involvement of facial and scapular
      muscles with eventual spreading to pelvic and lower limb muscles. A high degree
      of clinical variability with respect to age at onset, severity, and pattern of
      muscle involvement, both between and within families, is present. For this
      reason, diagnosis of FSHD1A can be sometimes difficult and molecular diagnosis is
      then necessary. A clinical and molecular genetic-based epidemiological
      investigation has been carried out in the territory of northwestern Tuscany in
      central Italy to calculate the prevalence rate of FSHD1A as of March, 2004. The
      molecular diagnosis has been based on the detection of large deletions of
      variable size of kpnI repeat units on chromosome 4q35. Results have been compared
      to those of a previous study conducted in the same area in 1981 (in the
      premolecular diagnosis era). The minimum prevalence rate was 4.60 x 10(-5)
      inhabitants, a value four times higher compared to our previous study. No
      significant correlation between fragment size and clinical severity has been
      observed. This study confirms in an Italian population a prevalence rate of
      FSHD1A similar to that observed in other populations. Furthermore, it underlines
      the usefulness of routine adoption of the genetic testing in confirming clinical
      suspicion of FSHD1A as well as in correctly diagnosing atypical and otherwise
      misclassified cases.

PMID- 15857185
TI  - APC germ-line mutations in southern Spanish patients with familial adenomatous
      polyposis: genotype-phenotype correlations and identification of eight novel
      mutations.
AB  - Familial adenomatous polyposis (FAP) is a disease characterized by the presence
      of hundreds of adenomatous polyps in the colon and rectum which, if not treated,
      develop into colorectal cancer. FAP is an autosomal dominantly inherited disorder
      caused by mutation in the APC gene. The aim of this study was to search for germ
      line mutations of the APC gene in unrelated FAP families from southern Spain. By
      direct sequencing of all APC gene exons, we found the mutation in 13 of 15
      unrelated FAP families studied. We identified eight novel mutations: 707delA
      (exon6), 730_731delAG (exon7), 1787C-->G and 1946_1947insG (exon14), 2496delC,
      2838_2839delAT, 2977A-->T, and 3224dupA (exon15). Two patients presented de novo
      germ-line mutations. Genotype-phenotype correlations for extraintestinal and
      extracolonic manifestations were studied. Intrafamilial phenotypic variability
      was observed in two families with mutations in exon/intron boundary, probably due
      to alternative splicing.

PMID- 15857186
TI  - Automatic scanning of interphase FISH for prenatal diagnosis in uncultured
      amniocytes.
AB  - Fluorescence in situ hybridization (FISH) of uncultured amniocytes using
      chromosome-specific DNA probes offers the opportunity for rapid aneuploidy
      screening. Between 80 and 95% of all chromosomal disorders expected in the second
      trimester of pregnancy can be discovered within 24 hr if DNA probes specific for
      chromosomes 21, 18, 13, X, and Y are used. Rapid results are crucial for clinical
      decision-making and are helpful in decreasing the anxiety level in most patients.
      One of the major factors that have been preventing the rapid FISH test from being
      broadly incorporated into the clinical setting is the limited staff in the
      cytogenetics laboratories. The present study demonstrates the use of an automated
      scanning system (Duet, BioView Ltd. Rehovot, Israel) for analyzing FISH in
      uncultured amniocytes. Fifty-six amniotic fluid samples were evaluated in
      parallel by karyotyping, manual FISH analysis, and automatic FISH scanning.
      Automatic scanning provided accurate results compared to both manual FISH scoring
      and karyotype analysis. The correlation between automatic and manual FISH
      scanning was found to be very high (r = 0.9, p < 0.0001). The availability of
      automation for aneuploidy screening in amniotic fluid samples will enable
      offering this test to a broader patient population while providing fast and
      reliable results.

PMID- 15857187
TI  - Knowledge, attitudes, and utilization of BRCA1/2 testing among women with early
      onset breast cancer.
AB  - A total of 2,400 questionnaires were mailed to members of two mid-Atlantic breast
      cancer awareness/support groups to investigate the association between attitudes,
      knowledge, and use of BRCA1/2 testing among women with early-onset breast cancer.
      Of the 493 (21%) questionnaires returned, 406 respondents had a diagnosis of
      breast cancer, of whom 248 were diagnosed prior to age 50 and included in the
      analyses. Eighty-three percent (206/248) of these women had heard of BRCA1/2
      testing and 12.5% (31/248) had undergone BRCA1/2 testing. Among women who had
      heard of BRCA1/2 testing, women who had been tested were younger (p = 0.03), more
      likely to have a college education (p = 0.03), more likely to have a family
      member who had undergone BRCA1/2 testing (p = 0.005), and had greater knowledge,
      more positive attitudes, and fewer negative attitudes about BRCA1/2 testing (p =
      0.02, p = 0.004, and p = 0.004, respectively). In this sample, knowledge
      regarding BRCA1/2 testing is high, but uptake of genetic testing is low. Lack of
      information regarding how genetic testing might alter health-care decisions and
      fear about the genetic testing procedure, its costs, and possible false-positive
      results are associated with low uptake of genetic testing. Further education
      regarding these specific points may enhance the use of genetic testing.

PMID- 15857188
TI  - Predictive testing for hereditary nonpolyposis colorectal cancer: subjective
      perception regarding colorectal and endometrial cancer, distress, and health
      related behavior at one year post-test.
AB  - This study evaluated illness representations, distress, and health-related
      behavior one year after disclosure of a predictive genetic test result for
      hereditary nonpolyposis colorectal cancer (HNPCC) in 36 carriers and 36
      noncarriers. Post-test, no significant differences between carriers and
      noncarriers were found in perceived risk and perceived seriousness of colorectal
      and endometrial cancer or in perceived control over endometrial cancer.
      Confidence in the controllability of colorectal cancer by means of medical
      examinations was higher for carriers than noncarriers post-test. Mean levels of
      distress (cancer-specific distress, state anxiety, psychoneuroticism) were within
      normal ranges and none of the participants had an overall pattern (on all scales)
      of clinically elevated levels of distress. Carriers had significantly higher
      cancer-related distress one year posttest than noncarriers. In both groups,
      colorectal cancer-related distress decreased. Noncarriers additionally showed
      decreased endometrial cancer-related distress and state anxiety. Within the year
      after testing, none of the noncarriers had a colonoscopy and all carriers where
      adherent to the recommendations regarding colorectal cancer screening. Although
      interview data delineated individually different problems specifically related to
      predictive testing (e.g., worry, difficulties in relation to other relatives,
      burden of regular follow-up), generally, predictive testing for HNPCC does not
      seem to induce major psychological problems. Moreover, the presented data are
      promising regarding the impact on health-related behavior.

PMID- 15857189
TI  - Risk assessment for inherited susceptibility to cancer: a review of the
      psychosocial and ethical dimensions.
AB  - The objective of this study was to conduct a broad-based systematic review of
      social, ethical, and legal considerations associated with genetic cancer risk
      assessment technologies (CaRATs). This paper focuses on psychosocial and ethical
      issues. Search results were limited to papers published in English, French, or
      German from January, 1990, to May, 2003. A quality assessment tool was developed
      and applied to retrieved papers. Application of the quality assessment tool
      resulted in 77 of 247 qualitative and quantitative primary research papers being
      reviewed and synthesized. A broad range of issues were addressed and grouped into
      content areas. Despite a large literature addressing psychosocial and ethical
      issues associated with CaRATs, many existing studies are not adequate to inform
      decision-makers and stakeholders. Careful policy analysis, as in some of the
      economic analyses reviewed here, is important to bridge this gap.

PMID- 15857190
TI  - DNA-based genetic testing is rising steeply in a national health care system with
      open access to services: a survey of genetic test use in Germany, 1996-2002.
AB  - The extent to which the fast-growing body of genetic knowledge is transferred
      into everyday clinical practice has nowhere been assessed in a systematic way.
      Available quantitative analyses of DNA-based genetic test provision and uptake
      rates are all concerned with specific test programs. The German health-care
      system is ideally suited for a more general approach, because it is highly
      flexible regarding access to services, thus permitting quick adjustments to
      sudden changes in particular subfields of medicine such as genetic testing. We
      have measured the amount of genetic service provision in Germany between 1996 and
      2002 by making use of the central database of the German national health-care
      system and by inquiring with private health insurance. We can document a three
      fold increase of DNA-based testing in the time period 1996-2002, whereas
      cytogenetic analyses and genetic counseling have remained constant. The growing
      body of genetic knowledge does indeed seem to be transferred into medical
      practice at an increasing rate, and the uptake rates are largely in proportion to
      test offers. DNA-based testing appears to be focussed on disease-associated germ
      line alterations.

PMID- 15857191
TI  - Acute syphilitic blindness in an HIV-positive patient.
AB  - This case report describes a rare manifestation of syphilis. An HIV-positive
      patient with severe immunosuppression presented with rapid loss of vision due to
      eye involvement of Treponema pallidum infection. The ophthalmologic examination
      on admittance showed a chorioretinitis, an uveitis, and a swollen optical disc of
      both eyes. Reconstitution of vision after application of intravenous penicillin
      occurred within 3 weeks. Despite low HIV prevalence in central Europe, behaviors
      that promote transmission of HIV and other sexually transmitted diseases tend to
      increase. The clinical presentation of syphilis may be atypical and the rate of
      complications is often higher in HIV-infected patients. Thus, Treponema pallidum
      infection should be considered in immunosuppressed HIV-positive patients
      presenting with chorioretinitis. Patients should receive treatment similar to
      that for neurosyphilis if there is suspicion of involvement of the central
      nervous system.

PMID- 15857192
TI  - Tumor necrosis factor-alpha levels in patients with HIV with wasting in South
      Asia.
AB  - Tumor necrosis factor (TNF)-alpha is thought to play an important role in
      wasting; but TNF-alpha levels have not been consistently found to be high in AIDS
      wasting. We conducted this study to determine any correlation between TNF-alpha
      levels and wasting in HIV-positive patients in a developing country. TNF-alpha
      levels were measured in four groups of patients: Group 1, HIV/AIDS with wasting
      (n = 25); group 2, HIV/AIDS without wasting (n = 47); group 3, HIV-negative
      patients with tuberculosis with wasting (n = 25); and group 4, healthy controls
      (n = 25). Wasting was defined as a body bass index (BMI) </=16.0 kg/m(2). TNF
      alpha was measured by a solid-phase sandwich enzyme linked immunosorbent assay
      (ELISA) kit. The mean BMI in HIV-positive patients with wasting (group 1) and
      without wasting (group 2) was 15.192 +/- 1.142 and 19.507 +/- 2.457,
      respectively, while group 3 and 4 had a BMI of 14.878 +/- 3.234 and 21.862 +/-
      2.763 kg/m(2). The mean TNF-alpha level in group 1 was 50.864 +/- 99.13 pg/mL and
      43.39 +/- 66.372 pg/mL in group 2. There was no significant difference between
      the two groups. TNF-alpha was significantly higher in the HIV/AIDS groups (group
      1 and 2) compared to the tuberculosis group (10.74 +/- 7.854) and healthy
      controls (5.846 +/- 3.40) at p = 0.01. TNF-alpha was significantly (p = 0.002)
      higher in symptomatic patients compared to asymptomatic patients (16.03 +/- 7.61
      versus 64.70 +/- 98.70). In conclusion, TNF-alpha levels were higher in HIV
      patients, regardless of the presence of wasting, compared to normal healthy
      controls of patients with tuberculosis with wasting.

PMID- 15857193
TI  - Increase in body cell mass and decrease in wasting are associated with increasing
      potency of antiretroviral therapy for HIV infection.
AB  - With the advent of potent combination antiretroviral therapy (ART), there has
      been a reduction in the incidence of wasting. However, few studies have
      investigated specific body composition changes associated with these treatments.
      This study aimed to investigate longitudinally the association of increasingly
      potent ART with changes in body cell mass and wasting utilizing bioelectric
      impedance analysis (BIA). In this longitudinal cohort study, 159 HIV-positive men
      were assessed semiannually from 1995 to 1997 for body composition utilizing BIA,
      CD4 lymphocyte count, HIV viral load, medical and depressive symptoms. Wasting
      was defined as body cell mass/height below the 90th percentile based on HIV
      positive norms. ART potency at each visit was scored utilizing published clinical
      guidelines, ranging from 1 (0-1 antiretrovirals) to 5 (3 or more antiretrovirals
      including a potent protease inhibitor). Viral resistance testing was not used.
      The mixed-effects model and the generalized estimating equations approaches were
      used to determine longitudinal correlates of body cell mass and of wasting,
      respectively. Over the 2 years of follow-up, potent combination ART use increased
      from 6% to 79%. Concurrently, a significant increase in mean body cell mass and a
      reduction in prevalence of wasting were seen, while total body weight, fat mass,
      and total body water did not change. Increasingly potent ART was associated with
      significant increases in body cell mass and reduction in wasting. Other
      significant correlates of increased body cell mass included higher CD4 count and
      decreased severity of HIV-related symptoms, fatigue and depression. The current
      study found that higher potency ART taken for relatively short term (2 years) was
      associated with an increase in body cell mass and a reduction in wasting and that
      these changes were associated with both medical (CD4, HIV symptoms) and
      behavioral (fatigue, depression) improvements. One caveat is this study did not
      distinguish among types of potent ART regimens. Given only some antiretrovirals
      appear linked to many body composition changes, regardless of their effect on
      viral load, it may be the type of regimen used that accounted for the
      relationship seen between viral load and body composition changes.

PMID- 15857194
TI  - Strategies for initiating combination antiretroviral therapy.
AB  - Numerous potent antiretroviral regimens have proven successful as initial therapy
      in treatment-naive HIV-infected patients. As the development of new agents makes
      possible new treatment regimens, providers are faced with increasingly complex
      questions of when to initiate treatment and which regimen to select for
      individual patients. Clinical trial data provide a foundation for choosing an
      initial regimen and play a key role in the formation of treatment guidelines
      issued by the United States Public Health Service and other organizations. This
      paper reviews the results of recent clinical trials focusing on initial therapy
      and addresses important considerations when beginning antiretroviral therapy
      (ART) in treatment-naive individuals.

PMID- 15857195
TI  - Recognition of undiagnosed HIV infection: an evaluation of missed opportunities
      in a predominantly urban minority population.
AB  - The goals of this study were to quantify delays in diagnosing HIV infection in
      patients presenting for medical care prior to the identification of their HIV
      infection, and to determine characteristics of visits preceding the
      identification of HIV infection. This was a retrospective cohort study of
      consecutive newly diagnosed HIV infected patients in a large urban setting.
      Patients were predominantly minorities and identified from all inpatient and
      outpatient HIV tests performed between December 29, 1998 and December 27, 1999.
      Data were collected from all emergency department and clinic visits for each
      patient included in this study for a 3-year period preceding the first diagnosis
      of HIV infection. Two hundred seventy-eight patients tested positive for HIV
      during the study period. Of these, 76 (27%) met inclusion criteria. Twenty-three
      patients made a total of 53 health care visits preceding the diagnosis of their
      HIV infection. The median delay in diagnosis of HIV infection was 2 days
      (interquartile range [IQR], 1-22 days; range, 0-1093 days) for all subjects,
      although 19 (25%; 95% confidence interval [CI]: 16%-36%) patients had a delay in
      diagnosis of 30 days or more. Among those patients who had made prior health care
      visits, the median delay in diagnosis was 112 days (IQR, 33-690 days; range, 2
      1093 days). No specific risk factor, historical clue, physical examination
      finding, or laboratory finding reliably identified patients with HIV infection.
      Documentation in the medical record of specific risk factors and clinical
      characteristics suggestive of HIV infection was poor. This study documented
      missed opportunities and delays in diagnosis of patients with unrecognized HIV
      infection. Clinicians must maintain a high index of suspicion for HIV infection
      in all patients.

PMID- 15857196
TI  - Achieving universal HIV screening in prenatal care in the United States: provider
      persistence pays off.
AB  - Routine voluntary HIV testing with the right to decline (the "opt-out" approach)
      is recommended for all pregnant women in the United States but not all are
      tested. We examined data from surveys of prenatal care providers to identify
      factors associated with universal testing among patients. Data are from a
      probability survey conducted in 1999 with prenatal care providers in four
      separate areas. Survey participants completed a self-administered questionnaire.
      We computed the percentage of providers reporting universal testing by
      characteristics of the provider's practice, medical specialty, how strongly they
      encouraged testing, perceptions of patients' risk, and whether they saw patients
      in public clinics. In the four locations (Brooklyn, New York; North Carolina;
      Connecticut; and Dade County, Florida) 95%-99% of providers reported that they
      routinely offered HIV testing to all pregnant women; the average percentage
      tested was 64%-89%. The percentage reporting that all of their patients were
      tested ranged from 12%-62%. The percent of providers reporting universal testing
      was positively associated with the degree to which testing was encouraged,
      particularly encouragement to women perceived to be low risk. In some areas,
      universal testing varied by medical profession, with obstetric physicians and
      residents, and nurse-midwives reporting a lower percentage of universal testing
      than family practice physicians and residents. To achieve the goal of routine HIV
      testing of all pregnant women, education and training must be delivered to all
      prenatal care providers. This training should emphasize the importance of routine
      testing. Even with the opt-out approach, many women may decline testing if their
      doctor does not recommend and encourage HIV testing.

PMID- 15857197
TI  - Rapid HIV testing of clients of a mobile STD/HIV clinic.
AB  - HIV rapid testing may enhance the effectiveness of a mobile HIV/sexually
      transmitted disease (STD) screening clinic in at-risk populations who normally do
      not seek care. Our goal was to determine the usability and post-test counseling
      rates of rapid HIV testing services for clients tested on a mobile clinic. HIV
      Oraquick rapid HIV-1 testing (OraSure Technologies, Inc., Bethlehem, PA) (blood)
      was offered to clients seeking HIV/STI counseling and testing services from the
      street at predetermined locations in areas of high STD morbidity, drug use, and
      commercial sex work. Rapid test results were available on the same day at the van
      within 10 minutes. Disease intervention specialists (DIS) attempted to locate and
      counsel positive clients who did not stay for results. By comparison, when
      offered at the same time, 64.5% of clients preferred Oraquick to traditional
      serologic testing. The post-test counseling rate for clients tested for Oraquick
      was 89% for infected and 93% for uninfected. By comparison, 11% of infected
      clients and 40% of uninfected clients tested for traditional test were post-test
      counseled. Clients who tested for the traditional enzyme immunoassay (EIA) test
      were told to return to the van in 14 days for results and post-test counseling.
      In the adjusted model, we also found statistically significant differences
      comparing clients who choose Oraquick to traditional serologic tests. These data
      suggest that rapid HIV testing services may enhance the effectiveness of mobile
      STD/HIV clinics.

PMID- 15857198
TI  - Rehabilitation in HIV/AIDS: development of an expanded conceptual framework.
AB  - In industrialized countries where HIV infection is becoming a chronic, episodic
      condition, rehabilitation services have the potential to play an expanded role
      for people living with HIV/AIDS (PLHAs). However, little is known about
      rehabilitation in the context of HIV. This paper documents the development of an
      enhanced, multidisciplinary conceptual framework of rehabilitation in the context
      of HIV, using the perceptions of PLHAs and rehabilitation professionals.
      Rehabilitation, broadly defined, is a dynamic process that includes all
      prevention and/or treatment activities and/or services that address body
      impairments, activity limitations and participation restrictions for an
      individual. The framework was developed through broad consultation and interviews
      with thirteen key informants. Themes that emerged from analysis of interviews
      related to concepts of rehabilitation in the context of HIV, rehabilitation
      professionals' roles in the context of HIV, and barriers to access and delivery
      of rehabilitation services. While there was some variation, key informants
      generally viewed rehabilitation as a goal-oriented and client-centered process
      with the potential to impact a range of life domains. Themes were presented to
      members of a national advisory committee (including PLHAs and health care
      providers), who produced the foundation of the HIV rehabilitation framework. The
      framework uses the perspective of the person living with HIV/AIDS, and includes
      individual life domains that may be affected by HIV, drawing and expanding upon
      the World Health Organization's (WHO's) International Classification of
      Functioning, Disability and Health.

PMID- 15857199
TI  - Watch co-infected patients more closely.

PMID- 15857200
TI  - Transmission differences between men and women.

PMID- 15857201
TI  - Isoflavone supplements exert hormonal and antioxidant effects in postmenopausal
      Korean women with diabetic retinopathy.
AB  - There is growing evidence that soy isoflavones exert hormonal and antioxidant
      effects in postmenopausal women. In the present study, 12 postmenopausal Korean
      women with diabetic retinopathy consumed 2 g of genistein combined
      polysaccharides (GCP), containing 120 mg of genistein and 57 mg of daidzein,
      daily for 12 weeks. Blood was collected prior to and after 12 weeks of GCP
      supplementation for analysis of fasting blood glucose, insulin, lipid profiles,
      sex hormone-binding globulin (SHBG), estradiol, testosterone, free testosterone,
      and osteocalcin and activities of glutathione peroxidase (GSH-Px), catalase, and
      paraoxonase. After GCP supplementation, blood glucose, insulin, total
      cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein
      cholesterols did not change significantly. However, there were significant
      increases in SHBG (P < .05) and testosterone (P < .05) and a decrease in
      estradiol (P < .01). Free testosterone levels were not significantly affected by
      GCP supplementation. After supplementation, osteocalcin decreased, but the
      difference was not statistically significant. Although activities of catalase and
      paraoxonase were unchanged, GSH-Px activity (P < .01) was increased
      significantly. These findings suggest that GCP supplementation may change the
      levels of some hormones and improve antioxidant status in postmenopausal Korean
      women with diabetic retinopathy.

PMID- 15857202
TI  - Wild blueberry-rich diets affect the contractile machinery of the vascular smooth
      muscle in the Sprague-Dawley rat.
AB  - Weanling male Sprague-Dawley rats were randomly fed a control diet (AIN-93) (C)
      or a blueberry diet (B) for 13 weeks, or a reverse diet (R) (C diet for 13 weeks,
      switched to the B diet for 8 weeks). Aortas were excised, and two intact and two
      endothelium-denuded rings were immersed in tissue baths containing physiological
      salt solution at 37 degrees C and aerated with 95% O(2) and 5% CO(2) (pH 7.4).
      Following equilibration and preconditioning under 1.5-g preload, cumulative dose
      response curves were generated with six doses of the alpha1-adrenergic receptor
      selective agonist L-phenylephrine (L-Phe, 10(8)-3 x 10(-6) M) and relaxed with
      one dose of acetylcholine (3 x 10(-6) M) to assess intact endothelium. The
      maximum force of contraction (Fmax) and vessel sensitivity (pD(2)) were
      determined in intact and endothelium-denuded rings. A two-way analysis of
      variance test revealed that blueberry-fed animals (B and R diets) developed a
      significantly lower F (max) (0.873 +/- 0.0463 and 0.9266 +/- 0.0463 g,
      respectively) when contracted with L-Phe, compared with the animals on the C diet
      (1.109 +/- 0.0463 g) (P < .05). The pD(2) of the intact rings was not
      significantly different among diet groups. Additionally, diet did not
      significantly affect the mean F (max) or pD(2) of endothelium-denuded rings. Our
      results indicate for the first time that wild blueberries incorporated into the
      diet affect the vascular smooth muscle contractile machinery by suppressing the
      alpha1-adrenergic receptor agonist-mediated contraction while having no effect on
      membrane sensitivity of the endothelial or vascular smooth muscle cell layer.
      Furthermore, their mechanism of action seems to be accomplished through an
      endothelium-dependent pathway.

PMID- 15857203
TI  - Effects of trans-resveratrol from Polygonum cuspidatum on bone loss using the
      ovariectomized rat model.
AB  - trans-Resveratrol (resveratrol) has been shown in several studies to
      significantly modulate biomarkers of bone metabolism. But, there is no direct
      evidence supporting its inhibitory effect towards bone loss. In the present
      study, effects of resveratrol on bone mineral density (BMD) and bone calcium
      content (BCC) were examined in the ovariectomized (OVX) rat model. Female Wistar
      rats were divided into four groups: SHAM group (sham-operated), OVX group (OVX
      control), OVX + ALD group (OVX and treated with 1.0 mg/kg of body weight of
      alendronate sodium), and OVX + RES group (OVX and treated with 0.7 mg/kg of body
      weight of resveratrol). Tested materials were given by gavage for 12 weeks after
      ovariectomy. Results showed that rats in the OVX, OVX + ALD, and OVX + RES groups
      had significantly higher body weights and feed efficiency than those in the SHAM
      group (P < .01). The OVX group had significantly lower femoral epiphysis BMD than
      the SHAM group, and epiphysis BMD in the OVX + ALD and OVX + RES groups was
      significantly greater than that in the OVX group (P < .05). However, the femoral
      midpoint BMD was not significantly different among the four groups. Additionally,
      animals in the OVX group had significantly lower BCC compared with the SHAM
      group, while the BCC of the OVX + ALD and OVX + RES groups was significantly
      higher than that of the OVX group (P < .05). These results indicated that
      resveratrol could increase epiphysis BMD and inhibit the decrease of femur BCC in
      OVX rats, suggesting that it could play a role in protecting against bone loss
      induced by estrogen deficiency.

PMID- 15857204
TI  - Bovine dialyzable leukocyte extract modulates the nitric oxide and pro
      inflammatory cytokine production in lipopolysaccharide-stimulated murine
      peritoneal macrophages in vitro.
AB  - Lipopolysaccharides (LPS) released from Gram-negative bacteria after infection
      initiate an exagerated response that leads to a cascade of pathophysiological
      events termed sepsis. Monocytes or macrophages produce many of the mediators
      found in septic patients. Targeting of these mediators, especially tumor necrosis
      factor (TNF)-alpha and nitric oxide (NO), has been pursued as a mean of reducing
      mortality in sepsis. Bovine dialyzable leukocyte extract (bDLE) is a dialysate of
      a heterogeneous mixture of low-molecular-weight substances released from
      disintegrated leukocytes of the blood or tissue lymphoid. In this study, to
      determine whether bDLE modulates NO and pro-inflammatory cytokine production,
      murine peritoneal macrophages were treated with bDLE (0.05 or 0.5 U/mL) before
      LPS (20 mg/mL) stimulation, and also LPS-stimulated murine peritoneal macrophages
      were treated with bDLE (0.05 or 0.5 U/mL) at 0, 4, 8, 12, and 24 hours. The bDLE
      significantly decreased NO production, and also decreased TNF-alpha and
      interleukin (IL)-6 but increased IL-10 production in LPS-stimulated murine
      peritoneal macrophages. Our results demonstrate that bDLE plays an important role
      in modulating TNF-alpha, IL-6, and NO production through IL-10, and this may
      offer therapeutic potential in clinical endotoxic shock.

PMID- 15857205
TI  - Effects of a Spirulina-based dietary supplement on cytokine production from
      allergic rhinitis patients.
AB  - Spirulina represents a blue-green alga that is widely produced and commercialized
      as a dietary supplement for modulating immune functions, as well as ameliorating
      a variety of diseases. We have previously shown that the in vitro culture of
      Spirulina with human peripheral blood mononuclear cells (PBMCs) modulated the
      production of cytokines. In the present study, we evaluated the impact of a
      Spirulina-based dietary supplement (Earthrise Nutritionals, Inc., Irvine, CA) on
      patients with allergic rhinitis by assessing the production of cytokines
      [interleukin (IL)-4, interferon (IFN)-gamma, and IL-2] critical in regulating
      immunoglobulin E-mediated allergy. In a randomized double-blinded crossover study
      versus placebo, allergic individuals were fed daily with either placebo or
      Spirulina, at 1,000 mg or 2,000 mg, for 12 weeks. PBMCs isolated before and after
      the Spirulina feeding were stimulated with phytohemagglutinin (PHA) prior to
      determining the levels of cytokine from cell culture supernatants. Although
      Spirulina seemed to be ineffective at modulating the secretion of Th1 cytokines
      (IFN-gamma and IL-2), we discovered that Spirulina, administered at 2,000 mg/day,
      significantly reduced IL-4 levels by 32% from PHA-stimulated cells. These results
      indicate that Spirulina can modulate the Th profile in patients with allergic
      rhinitis by suppressing the differentiation of Th2 cells mediated, in part, by
      inhibiting the production of IL-4. To our knowledge, this is the first human
      feeding study that demonstrates the protective effects of Spirulina towards
      allergic rhinitis.

PMID- 15857206
TI  - The effects of dietary naringenin supplementation on physiological changes in
      molar crestal alveolar bone-cemento-enamel junction distance in young rats.
AB  - The objective of this study was to evaluate the influence of dietary naringenin
      (NAR) supplementation on physiological molar crestal alveolar bone (CAB)-cemento
      enamel junction (CEJ) distances in young male albino rats. The effects of diets
      supplemented with 0.09%, 0.18%, 0.36%, and 0.72% NAR, at the expense of dextrose,
      were tested on 40 young rats, divided equally into five groups, for a period of
      42 days. Rat skulls were defleshed, and CAB-CEJ distance was scored according to
      the modified method of Keyes and Gold. Data were analyzed using one-way analysis
      of variance, post hoc Tukey's test, and Spearman's (R(2)) correlation. P < .05
      was used to reject the null hypothesis. NAR showed a statistically significant
      inverse dose-dependent relationship on CAB-lingual alveolar bone distance (P <
      .05). In all cases lingual CAB-CEJ distance was larger than buccal CAB-CEJ
      distance. Thus dietary NAR supplementation was shown to significantly reduce
      molar CAB-CEJ distance (P < .001-.05) during alveolar development in young male
      rats.

PMID- 15857207
TI  - Antibacterial screening of anthocyanic and proanthocyanic fractions from
      cranberry juice.
AB  - The effect of anthocyanin- and proanthocyanidin-rich fractions isolated from
      cranberry juice was studied for their antibacterial activity against nine
      bacterial strains. Activity was assessed by the agar diffusion assay.
      Staphylococcus aureus ATCC 6538 was the only strain to exhibit some
      susceptibility to four out of 10 anthocyanin-rich fractions tested. A variable
      susceptibility of S. aureus, Enterococcus faecalis ATCC 10541, and Micrococcus
      luteus ATCC 9341 to proanthocyanidin- rich fractions was also observed.
      Streptococcus mutans strains as well as Escherichia coli ATCC 10538 and
      Pseudomonas aeruginosa ATCC 27853 were not susceptible to any of the cranberry
      juice samples or fractions at the tested concentrations. There was no clear
      correlation between Gram-positive or Gram-negative bacterial susceptibility to
      cranberry juice. In this work, the role of cranberry juice anthocyanic and
      proanthocyanic fractions upon bacterial viability is discussed.

PMID- 15857208
TI  - Comparison of the antioxidant activities of nine different fruits in human
      plasma.
AB  - Oxidative stress in humans is associated with damage to DNA, proteins, and
      biological membranes. Oxidative stress, which often arises as a result of an
      imbalance in the human antioxidant status, has been implicated in aging and a
      number of human diseases such as cancer, atherosclerosis, and rheumatoid
      arthritis. This study was performed to test the hypothesis that the consumption
      of fruit juices may improve antioxidant status in human plasma. Ten healthy men
      25-26 years old were recruited for the study. After overnight fasting, study
      subjects were fed 150 mL of fruit juice, and blood was collected at 0, 30, 60,
      90, and 120 minutes after consumption. After a 1-day wash-out period, subjects
      were fed with the next sample of fruit juice until all nine juices (pear, apple,
      orange, grape, peach, plum, kiwi, melon, and watermelon) had been evaluated. All
      juices were prepared from pure fruits ground in a home-style mixer. Dietary food
      records and anthropometric measurements were used to evaluate the nutritional
      status of subjects. The antioxidant activities of fruit juices were estimated by
      measuring antioxidant status in the plasma using dichlorofluorescein (DCF)
      fluorescence. Except for pear juice, eight kinds of juices exhibited potent
      antioxidant effects in human plasma. Within 30 minutes after consumption, orange,
      melon, grape, peach, plum, apple, and kiwi juices already effectively suppressed
      reactive oxygen species generation. This radical scavenging effect of fruit
      juices was maintained for up to 90 minutes post-consumption, but the relative DCF
      fluorescence had rebounded to near the initial levels at 2 hours post-consumption
      in most samples tested. Interestingly, however, grape juice continuously exerted
      persistent antioxidant activity until 2 hours after supplementation. These
      results suggest that the consumption of fruits or fruit juices may reduce damage
      from oxidative stress, and that this effect may be a consequence of the
      antioxidant activity of fruits in scavenging the reactive oxygen species
      generated in human plasma. However, long-term studies with more subjects are
      needed to provide additional supportive evidence and better characterize the
      antioxidant properties of natural fruit juices.

PMID- 15857209
TI  - Green tea extract and catechin ameliorate chronic fatigue-induced oxidative
      stress in mice.
AB  - Chronic fatigue syndrome (CFS) is an illness characterized by persistent and
      relapsing fatigue, often accompanied by numerous symptoms involving various body
      systems. The etiology of CFS remains unclear, but a number of studies have shown
      that oxidative stress may be involved in its pathogenesis. The present study was
      designed to investigate the protective effect of green tea extract (GTE) and
      catechin in the mouse model of CFS. Animals were subjected to a forced swimming
      test session of 6 minutes every day for 7 days; a significant increase in
      immobility time on successive days represented the CFS in mice. Biochemical
      analysis revealed that the chronic swim test significantly increased lipid
      peroxidation levels and decreased glutathione levels in mouse whole-brain
      homogenate. Treatment with GTE (25 or 50 mg/kg, i.p.) and catechin (50 or 100
      mg/kg, i.p.) for 7 days reversed the increase in immobility time. Protection was
      correlated with the lowered levels of lipid peroxidation and restoration of
      reduced glutathione levels in the brains of fatigued mice. These findings
      strongly suggest the pivotal role of oxidative stress in the pathophysiology of
      CFS and that GTE and catechin could be used as potential agents in the management
      of CFS and warrant the inclusion of GTE and catechin in the treatment regimen of
      CFS patients.

PMID- 15857210
TI  - A randomized, double-blind and placebo-controlled study of a Ganoderma lucidum
      polysaccharide extract in neurasthenia.
AB  - Ganoderma lucidum has been widely used to treat various diseases, including
      cancer, diabetes, and neurasthenia in many Asian countries. This randomized,
      double-blind, placebo-controlled parallel study aimed to investigate the efficacy
      and safety of a polysaccharide extract of G. lucidum (Ganopoly) in Chinese
      patients with neurasthenia. One hundred thirty-two patients with neurasthenia
      according to the diagnosis criteria of the 10th International Classification of
      Diseases were included in this study. Written consents were obtained from the
      patients, and the study was conducted in accordance with Good Clinical Practice
      guidelines. Patients were randomized to receive Ganopoly or placebo orally at
      1,800 mg three times a day for 8 weeks. Efficacy assessments comprised the
      Clinical Global Impression (CGI) improvement of severity scale and the Visual
      Analogues Scales for the sense of fatigue and well-being. In 123 assessable
      patients in two treatment groups at the end of the study, Ganopoly treatment for
      8 weeks resulted in significantly lower scores after 8 weeks in the CGI severity
      score and sense of fatigue, with a respective reduction of 15.5% and 28.3% from
      baseline, whereas the reductions in the placebo group were 4.9% and 20.1%,
      respectively. The score at day 56 in the sense of well-being increased from
      baseline to 38.7% in the Ganopoly group compared with 29.7% in the placebo group.
      The distribution of the five possible outcomes from very much improved to
      minimally worse was significantly different (X (2) = 10.55; df = 4; P = .0322)
      after treatment with Ganopoly or placebo. There was a percentage of 51.6% (32 of
      62) in the Ganopoly group rated as more than minimally improved compared with
      24.6% (15 of 61) in the placebo group (X (2) = 9.51; df = 1; P = .002). Ganopoly
      was well tolerated in the study patients. These findings indicated that Ganopoly
      was significantly superior to placebo with respect to the clinical improvement of
      symptoms in neurasthenia.

PMID- 15857211
TI  - Therapeutic effect of D-002 (abexol) on gastric ulcer induced experimentally in
      rats.
AB  - D-002 is a mixture of higher aliphatic primary alcohols isolated from beeswax,
      wherein triacontanol is the most abundant alcohol, with antioxidant and anti
      ulcer properties. Since compounds with cytoprotective and antioxidant effects can
      improve healing of gastroduodenal ulcer induced by noxious agents, this work
      investigated the healing effect of D- 002 on acute and chronic gastric ulcers
      induced with indomethacin and acetic acid, respectively, in rats. Acute gastric
      ulcer was induced with single oral doses of indomethacin (20 mg/kg). Treatments
      with D-002 at 50, 100, and 200 mg/kg or vehicle were administered 3 hours after
      ulcer induction. Three hours later, rats were sacrificed, and the stomach was
      removed for quantifying the lesions. Chronic gastric ulcer was induced by 50
      microL of 80% acetic acid application on the anterior serosal surface of the
      glandular stomach during 20 seconds. Twenty-four hours later D-002 at 50, 100,
      and 200 mg/kg or vehicle was administered for 5 days. At the end of the
      treatment, animals were fasted for 24 hours and sacrificed, the stomachs were
      removed, and the lesions were quantified. D-002 orally administered at 100 and
      200 mg/kg acutely significantly healed gastric ulcers induced with indomethacin
      by 39% and 56% compared with positive controls, respectively. Also, D-002 at 200
      mg/kg, but not at 50 or 100 mg/kg, administered orally for 5 days after ulcer
      induction exerted a significant healing effect (65.8% inhibition) in gastric
      ulcers induced with acetic acid. In conclusion, this work demonstrated that D-002
      administered after ulcer induction induced effective healing of acute and chronic
      gastric ulcers provoked by, respectively, indomethacin and acetic acid.

PMID- 15857212
TI  - Effects of D-002, a product isolated from beeswax, on gastric symptoms of
      patients with osteoarthritis treated with piroxicam: a pilot study.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are indicated for treatment of
      rheumatoid arthritis and osteoarthritis, but often induce gastric adverse
      experiences (AE), including gastric ulcers and complications. Inhibitors of
      proton pump and H(2) antagonists are very effective for duodenal ulcer;
      meanwhile, cytoprotective drugs are more effective for gastric ulcer. D-002 is a
      mixture of higher aliphatic alcohols obtained from beeswax, wherein triacontanol
      is the most abundant. D-002 induces anti-ulcer effects through a cytoprotective
      mechanism, being more effective in protecting against ethanol- and NSAID-induced
      ulcers. The present double-blind, placebo-controlled clinical study was
      undertaken to investigate the effects of D-002 on gastric symptoms associated to
      piroxicam use on patients suffering osteoarthritis. Fifty-nine patients, all
      taking piroxicam, 20 mg/day, were randomized to placebo or D-002 (40 or 100
      mg/day) for 14 days. The primary efficacy variable was the reduction on the
      frequency of patients with gastric AE compared with placebo. Pain evolution was
      investigated to discard any influence on D-002 on the analgesic effect of
      piroxicam. The frequency of patients treated with D-002, 40 and 100 mg/day,
      reporting acidity [0 of 18 (0%) and 1 of 21 (4.8%), respectively] was lower (P <
      .05) than in placebo [6 of 20 (30%)]. Also, the frequency of patients treated
      with 100 mg/day reporting some gastric AE [5 of 21 (23.8%)] was lower (P < .05)
      than in placebo [13 of 20 (65.0%)]. The analgesic effect of piroxicam was
      unaffected with D-002. Treatment was well tolerated. Two patients discontinued
      from the study because of gastrointestinal AE: one in the placebo group and the
      other treated with D-002, 40 mg/day. Other three patients discontinued because of
      other AE: mildly uncontrolled hypertension (one in the placebo group, one treated
      with D-002, 40 mg/day) and headache (one treated with D-200, 100 mg/day). It is
      concluded that D-002 could be useful for controlling gastric AE of patients
      treated with NSAIDs, although further studies with a larger sample size and
      longer follow-up are needed for definitive conclusions.

PMID- 15857213
TI  - Glycoprotein isolated from Solanum nigrum L. modulates the apoptotic-related
      signals in 12-O-tetradecanoylphorbol 13-acetate-stimulated MCF-7 cells.
AB  - Solanum nigrum L. (SNL) has been used in folk medicine for its anti-inflammatory
      activity. We isolated only the SNL glycoprotein from SNL and found that it was
      cytotoxic at low concentration. With respect to cytotoxicity, we investigated
      whether purified SNL glycoprotein is able to regulate protein kinase C (PKC)
      alpha activation and nuclear factor (NF)- kappaB activities in 12-O
      tetradecanoylphorbol 13-acetate (TPA)-induced tumor promotion, and whether it has
      an apoptosis-inducing effect in MCF-7 cells using western blot analysis. In
      addition, to elucidate the relationship between PKCalpha and NF-kappaB,
      inhibitory studies were performed with staurosporine (an inhibitor of
      phospholipid/calcium-dependent protein kinase) and pyrrolidine dithiocarbamate
      (an inhibitor of NF-kappaB activation). To verify induction of apoptosis by the
      SNL glycoprotein, we performed DNA fragmentation and nuclear staining assays
      using ethidium bromide and bisbenzamide H33342. The results in this study
      indicated that SNL glycoprotein induces apoptosis through modulation of PKCalpha
      and NF-kappaB activity in MCF-7 cells. In fact, SNL glycoprotein interfered with
      PKCalpha membrane translocation and inhibited NF-kappaB (p50) protein activity in
      MCF-7 cells stimulated with TPA (61.68 ng/mL, 100 nM) dose-dependently. Regarding
      the apoptotic-inducing effect, nucleosomal DNA fragmentation and nuclear staining
      by SNL glycoprotein in MCF-7 cells were shown. Collectively, the data demonstrate
      that SNL glycoprotein is a potential natural anticancer agent because of its
      ability to induce apoptosis in MCF-7 cells.

PMID- 15857214
TI  - Antinociceptive and anti-inflammatory effects of the saponin and sapogenins
      obtained from the stem of Akebia quinata.
AB  - The stem of Akebia quinata Decasisne (Lardizabalaceae) has been used to treat
      urinary tract inflammatory disease. It has been reported that saponins in
      medicinal plants may act as bioactive components after biodegradation to
      sapogenins in the gastrointestinal tract. To find the active components, we
      obtained the methanol (MeOH) extract from A. quinata stems and fractionated this
      extract into CHCl(3), butanol (BuOH), and H(2)O fractions. A saponin-containing
      BuOH fraction was refluxed in an acidic solution to yield the hydrolyzed
      fraction. Silica gel column chromatography separated kalopanaxsaponin A (1) from
      the BuOH fraction, and oleanolic acid (2) and hederagenin (3) were obtained from
      the hydrolyzed fraction. The antinociceptive effect was tested by hot plate
      writhing and tail-flicks methods using mice, and the anti-inflammatory effect was
      assayed using carrageenan-induced rat edema against the following samples: the
      MeOH extract of A. quinata stems, its fractions, the isolated saponin,
      kalopanaxsaponin A, and the sapogenins hederagenin and oleanolic acid. The MeOH
      extract exhibited antinociceptive/anti-inflammatory effects by oral
      administration of 100 and 250 mg/kg doses, indicating that the MeOH extract has
      an antinociceptive/anti-inflammatory activity. The BuOH fraction (crude saponin)
      also significantly exhibited those bioactivities. Treatments with 10 and 30 mg/kg
      perorally of these two sapogenins produced significant antinociceptive/ anti
      inflammatory effects in the rat, suggesting that the sapogenins may act as
      resultant active compounds. Compounds 2 and 3 inhibited dye leakage into the
      peritoneal cavity induced by acetic acid, and the latter was more active than the
      former. The anti-inflammtory effects were further supported by the reduction of
      carrageenan-induced lipid peroxidation and hydroxy radical content in serum.
      These results suggest that the antinociceptive/anti-inflammatory properties of
      the stem of A. quinata can be attributed to the sapogenins oleanolic acid and
      hederagenin.

PMID- 15857215
TI  - Du-zhong (Eucommia ulmoides Oliv.) cortex water extract alters heme biosynthesis
      and erythrocyte antioxidant defense system in lead-administered rats.
AB  - This study examined the ameliorative effect of a Du-zhong (Eucommia ulmoides
      Oliv.) cortex water extract (DzCw) on heme biosynthesis and erythrocyte
      antioxidant enzyme activities in lead (Pb)-administered rats. Male rats were
      divided into three groups: normal control group, Pb control group (Pb), and DzCw
      administered Pb group (Pb + DzCw). The Pb (25 mg/kg of body weight) was
      administered orally once a week for 4 weeks, while the DzCw was administered
      orally at a dosage of 0.139 g of DzCw/kg of body weight/day. DzCw administration
      significantly lowered plasma Pb concentration compared with the Pb group.
      Furthermore, the blood hematocrit and hemoglobin levels were significantly higher
      in the Pb + DzCw group than in the Pb group. Although the blood and hepatic delta
      aminolevulinic acid dehydratase (ALAD) activities were significantly lower in the
      Pb group compared with the normal control group, both ALAD activities was
      normalized with the administration of DzCw. The erythrocyte superoxide dismutase
      and catalase activities were significantly higher in the Pb group than in the
      normal control group, whereas the glutathione peroxidase activity and glutathione
      level were lowered by Pb administration compared with the normal group. However,
      the administration of DzCw was found to enhance the antioxidant defense system
      and significantly lower lipid peroxidation levels in erythrocytes compared with
      the Pb group. These results indicate that the DzCw administration alleviated the
      Pb-induced oxidative stress in the erythrocytes through elevating the blood and
      hepatic ALAD activity and enhancing the antioxidant enzyme activities.

PMID- 15857216
TI  - Anti-inflammatory activity of Cleome gynandra L. on hematological and cellular
      constituents in adjuvant-induced arthritic rats.
AB  - Cleome gynandra L. (cat whiskers) has traditionally been used for the treatment
      of rheumatic and other inflammatory conditions. In this work, the methanolic
      extract of the leaves of C. gynandra exhibited significant anti-inflammatory
      activity in adjuvant-induced arthritic rats. Phytochemical screening was carried
      out to ascertain the qualitative composition of the leaves. Arthritis was induced
      by Freund's complete adjuvant. A significant decrease in paw edema with a
      remarkable increase in body weight was observed following oral administration of
      the leaf extract (150 mg/kg of body weight). The alterations in hematological and
      other biochemical parameters were restored to near normal after a treatment
      period of 30 days. These results demonstrate that the plant extract has no
      harmful effect and exerts in vivo anti-inflammatory properties against adjuvant
      induced arthritis.

PMID- 15857217
TI  - Antibacterial activity of 13 honeys against Escherichia coli and Pseudomonas
      aeruginosa.
AB  - In this study the activity of 13 honeys, including three commercial antibacterial
      honeys, against Escherichia coli and Pseudomonas aeruginosa was determined.
      Antibacterial activity of the honeys was assayed using standard well diffusion
      methods. All honeys, and an artificial honey, were tested at four concentrations
      (10%, 5%, 2.5%, and 1% wt/vol) against E. coli and P. aeruginosa, and zones of
      inhibition were measured. All honeys tested had an inhibitory effect on the
      growth of E. coli and P. aeruginosa, with one honey still having activity against
      E. coli and three having activity against P. aeruginosa at 2.5%. No honey was
      active at 1% concentrations. E. coli was more susceptible to inhibition by the
      honeys used in this study than was P. aeruginosa. In this study we have
      demonstrated that several honeys, in addition to commercial antibacterial honeys,
      can inhibit E. coli and P. aeruginosa and may have potential as therapeutic
      honeys.

PMID- 15857218
TI  - Passionflower fruit-a "new" source of lycopene?
AB  - Many population studies have established a link between dietary intake of the
      carotenoid antioxidant lycopene and a reduced risk of chronic diseases. Unlike
      most carotenoids, lycopene occurs in a few places in the diet. Besides tomatoes
      and tomato products, major sources of lycopene, other lycopene-rich foods include
      watermelon, pink grapefruit, pink guava, and papaya. Dried apricots and pureed
      rosehips contain relatively large amounts, too. In our study we found that
      passionflower fruit (skin and pericarp) contains a great amount of lycopene,
      whereas the content of other carotenoids is very low, and almost inexistent. This
      edible fruit could be an alternative source of a potential important nutrient for
      those people who do not eat tomatoes and tomato products.

PMID- 15857219
TI  - Anti-HIV protease activity from rosa family plant extracts and rosamultin from
      Rosa rugosa.
AB  - To identify substances with anti-human immunodeficiency virus (HIV) activity from
      plant sources, 12 extracts of Rosa family plants were screened for their
      inhibitory effects against HIV-1 protease. Of the extracts tested, the strongest
      inhibitory effects were observed in the root of Rosa rugosa and the leaves of
      Prunus sargentii, at a concentration of 100 microg/mL. Rosamultin isolated from
      the root of R. rugosa inhibited HIV-1 protease by 53% at a concentration of 100
      microM.

PMID- 15857220
TI  - Determination of mineral contents of Turkish herbal tea (Salvia aucheri var.
      canescens) at different infusion periods.
AB  - Inductively coupled plasma atomic emission spectrometry has been used for the
      determination of contents of major and minor elements in Salvia aucheri var.
      canescens (sage) and its infusions for different intervals. Twenty-five elements
      (Al, B, Ba, Bi, Ca, Cd, Co, Cr, Cu, Fe, Ga, Ln, K, Li, Mg, Mn, Na, Ni, P, Pb, S,
      Sr, Ti,V, and Zn) were detected in both S. aucheri and its infusions. The ranges
      of mineral levels varied from Cd (1.6668 mg/kg) to K (13,570 mg/kg) and Ni
      (0.05273 mg/kg) to K (196.25 mg/kg) in the herb and its infusions, respectively.
      The levels of K, Ca, Na, Mg, and S in all infusions in this work were higher than
      those of the other elements. However, Al, Ba, Ca, Cd, Co, Cu, Fe, Li, K, Mg, Na,
      Ni, P, Pb, Sr, Ti, and Zn contents were high in the first period of infusion. As
      a result, the first period of infusion may be proposed as the optimum infusion
      time because of nutritional properties. These results may be useful for the
      evaluation of dietary information.

PMID- 15857221
TI  - Comparison of different fibers for in vitro production of short chain fatty acids
      by intestinal microflora.
AB  - The fermentation of dietary fiber in the large intestine and the by-products of
      this fermentation are thought to protect against colonic diseases. As it is
      difficult to measure the fermentation of dietary fiber in an intact animal, in
      vitro techniques have been developed to compare the fermentability of various
      dietary fibers. The objective of this project was to compare short chain fatty
      acid (SCFA) production with different fibers in an in vitro fermentation model. A
      wide range of commercially available dietary fiber sources was compared for SCFA
      production. Fibers were fermented with a fecal innoculum for 0, 2, 4, 8, 12, and
      24 hours. SCFAs were measured by gas chromatography. SCFA production varied among
      the fiber sources. Hydrolyzed guar gum and galactomannan produced the greatest
      amounts of total SCFAs. Butyrate production was higher with the fiber sources
      than the glucose control. Acetate production was less for psyllium than the other
      fibers. Thus, different dietary fiber sources are more readily fermented by fecal
      microflora. These differences most likely affect the physiological differences
      seen among dietary fiber sources.

PMID- 15857222
TI  - Hyper- or hypoleptinemia in subjects with zinc deficiency?

PMID- 15857224
TI  - Optimal insulin pump dosing and postprandial glycemia following a pizza meal
      using the continuous glucose monitoring system.
AB  - BACKGROUND: We attempted to identify an optimal insulin pump meal bolus by
      comparing postprandial sensor glucose values following three methods of insulin
      pump meal bolusing for a consistent pizza meal. RESEARCH DESIGN AND METHODS:
      Twenty-four patients with type 1 diabetes participated in a study to compare
      postprandial glucose values following three meal bolus regimens for a consistent
      evening pizza meal. Each participant utilized the following insulin lispro
      regimens on consecutive evenings, and glucose values were tracked by the
      Continuous Glucose Monitoring System (CGMS, Medtronic MiniMed, Northridge, CA):
      (a) single-wave bolus (100% of insulin given immediately); (b) 4-h dual-wave
      bolus (50% of insulin given immediately and 50% given over a 4-h period); and (c)
      8-h dual-wave bolus (50% of insulin given immediately and 50% given over a 8-h
      period). Total insulin bolus amount was kept constant for each pizza meal.
      RESULTS: Divergence in blood glucose among the regimens was greatest at 8-12 h.
      The 8-h dual-wave bolus provided the best glycemic control and lowest mean
      glucose values (singlewave bolus, 133 mg/dL; 4-h dual-wave bolus, 145 mg/dL; 8-h
      dual-wave bolus, 104 mg/dL), leading to a difference in mean glucose of 29 mg/dL
      for the single-wave bolus versus the 8-h dual-wave bolus and 42 mg/dL for the 4-h
      dual-wave bolus versus the 8-h dual-wave bolus. The lower mean glucose in the 8-h
      dual-wave bolus was not associated with any increased incidence of hypoglycemia.
      CONCLUSIONS: Use of a dual-wave bolus extended over an 8-h period following a
      pizza meal provided significantly less postprandial hyperglycemia in the late
      postprandial period (8-12 h) with no increased risk of hypoglycemia.

PMID- 15857225
TI  - Impact of modem-transferred blood glucose data on clinician work efficiency and
      patient glycemic control.
AB  - BACKGROUND: Communication of blood glucose (BG) results between patients and
      health care providers (HCPs) is of established benefit and remains a critical
      part of the diabetes management process. Currently, HCPs typically receive BG
      data from patients at the time of clinic visits or by telephone. The Accu-Chek
      Acculink modem (Roche Diagnostics Corp., Indianapolis, IN) provides an additional
      and attractive option that can potentially facilitate this communication.
      METHODS: To assess the impact of modem transfer of BG, we studied 47 participants
      with diabetes enrolled in a diabetes education program. Subjects were randomized
      to weekly communication of BG data to their HCP by either telephone (n = 23) or
      modem (n = 24) for 4 weeks. Mean age (+/- SD) was 44 +/- 15 years, 62% were
      female, 74% used insulin, 53% had type 1 diabetes, and mean baseline glycosylated
      hemoglobin (A1C) was 8.8% (range 5.2-13.2%). RESULTS: There were no differences
      between groups in the amount of time the HCP spent analyzing BG data and
      communicating with patients (12.6 +/- 6.1 min/week in the telephone group and
      11.5 +/- 5.1 min/week in the modem group) or in the number of patient and HCP
      attempts needed to make contact. There were similar improvements in A1C between
      groups (change of -0.4 +/- 0.7% in the telephone group and -0.9 +/- 1.4% in the
      modem group, P = 0.18). BG data provided by telephone had a 6% error rate, in
      contrast to modem-sent data, which were transmitted without error. CONCLUSIONS:
      Modem transfer of BG data can provide an accurate and clinically useful option
      for communication between patients and their HCP and has comparable effects on
      A1C.

PMID- 15857226
TI  - Analysis: transfer of the data collected by the patient to the health care
      providers: problems and solutions.

PMID- 15857227
TI  - A novel approach to continuous glucose analysis utilizing glycemic variation.
AB  - BACKGROUND: Various methodologies have been proposed for analysis of continuous
      glucose measurements. These methods have mainly focused on the proportion of low
      or high glucose readings and have not attempted to analyze other dimensions of
      the data obtained. This study proposes an algorithm for analysis of continuous
      glucose data including a novel method of assessing glycemic variability. METHODS:
      Mean blood glucose and mean of daily differences (MODD) assessed the degree that
      the Continuous Glucose Monitoring System (CGMS, Medtronic MiniMed, Northridge,
      CA) trace was representative of the 3-month glycemic pattern. Percentages of
      times in low, normal, and high glucose ranges were used to assess marked glycemic
      excursion. Continuous overall net glycemic action (CONGA), a novel method
      developed by the authors, assessed intra-day glycemic variability. These methods
      were applied to 10 CGMS traces chosen randomly from those completed by children
      with type 1 diabetes from the Royal Children's Hospital, Melbourne, Victoria,
      Australia and 10 traces recorded by healthy volunteer controls. RESULTS: The
      healthy controls had lower values for mean blood glucose, MODD, and CONGA.
      Patients with diabetes had higher percentages of time spent in high and low
      glucose ranges. There was no overlap between the CONGA values for patients with
      diabetes and for controls, and the difference between controls and patients with
      diabetes increased markedly as the CONGA time period increased. CONCLUSIONS: We
      advocate an approach to the analysis of CGMS data based upon a hierarchy of
      relevant clinical questions alluding to the representative nature of the data,
      the amount of time spent in glycemic excursions, and the degree of glycemic
      variation. Integrated use of these algorithms distinguishes between various
      patterns of glycemic control in those with and without diabetes.

PMID- 15857228
TI  - A graphical user interface for diabetes management that integrates glucose
      prediction and decision support.
AB  - BACKGROUND: The promise of the Diabetes Control and Complications Trial (DCCT)
      has yet to be realized in clinical practice. Notwithstanding intensive education
      and intensified therapy, there is a distinct lack of a suitable alternative to
      the intensive decision support that was also provided in the DCCT. Recently, a
      novel glucose predicting engine has been developed and validated. Use of its
      predictions in decision support in respect to medication dosing, diet, exercise,
      and stress promises to empower patients to achieve better diabetes control while
      reducing hypoglycemia and preventing body weight gain. A graphical user interface
      (GUI) suitable for these purposes is here described. METHODS: The kernel of the
      GUI is a registry database located on a server accessible to both patients and
      their providers. The patient-GUI includes the resources of the glucose predicting
      engine and user-friendly, intuitive means to enter body weight and all home
      monitored blood glucose levels. In response, means to modify medication dosages
      (dosing decision support) and modify planned diet and physical activity
      (lifestyle decision support) are afforded the user. Each action is animated so
      that the patient can visually see the impact of his or her changes on predicted
      glucose outcomes and the pending risks of hypoglycemia. RESULTS: A staged
      sequence of screens supports the self-management tasks, including selection of
      the current meal period, the entry of data, and documentation. The GUI returns
      current medications and presents up-down buttons for adjusting dosages, for
      changing carbohydrates, for changing exercise, and for predicting the effects of
      stress. For each adjustment, the impact on medications or predicted glycemia
      outcomes is animated. CONCLUSIONS: A new GUI that incorporates a novel glucose
      predicting engine is intended for all insulin-treated patients with diabetes. It
      may help patients and their providers to realize better glycemic control and
      thereby achieve the promise of the DCCT.

PMID- 15857229
TI  - Targeted glycemic reduction in critical care using closed-loop control.
AB  - BACKGROUND: Critically ill patients are often hyperglycemic and extremely diverse
      in their dynamics. Consequently, fixed protocols and sliding scales can result in
      error and poor control. Tight glucose control has been shown to significantly
      reduce mortality in critical care. An improved physiological system model of the
      glucose-insulin dynamics of a critical care patient is used to develop an
      adaptive tight glucose control protocol that accounts for variable patient
      dynamics, and is verified in limited clinical trials. METHODS: A physiologically
      based two-compartment system model that accounts for time-varying insulin
      sensitivity, time-varying endogenous glucose removal, and two saturation kinetics
      mechanisms is developed. A bolus-based adaptive control protocol is developed
      that monitors the physiological status of a critically ill patient, enabling
      tight glycemic regulation to preset glycemic targets. The model and protocol are
      verified in three, 5-h preliminary proof-of-concept clinical trials. Ethics
      approval was granted by the Canterbury Ethics Committee (Christchurch, New
      Zealand). RESULTS: Preset glycemic targets are achieved with an average absolute
      error of 9%, with 75% of all targets achieved within the 7% measurement error.
      Absolute errors greater than 7% ranged from 17% to 21%. CONCLUSIONS: Tight
      stepwise control was exhibited in all cases, and the adaptive system was able to
      match the model and observed patient dynamics. Most errors are associated with
      external perturbations such as drug therapies, or mismodeled parameters that can
      be easily adjusted with longer trials and/or more data per hour. The overall
      result is targeted stepwise tight glycemic regulation using insulin boluses.

PMID- 15857230
TI  - Evaluation of a new blood glucose monitoring system with auto-calibration.
AB  - BACKGROUND: The Ascensia CONTOUR System (Bayer HealthCare LLC, Elkhart, IN) is a
      new blood glucose (BG) monitoring system (BGMS) that uses glucose dehydrogenase
      chemistry and that combines low sample volume, fast response time, an auto
      control marking feature, and an auto-calibration function in a small package.
      METHODS: The system was evaluated at four diabetes clinics with ambulatory
      subjects who had diabetes. The BGMS was tested by both health care professionals
      (HCPs) and lay users. It was also evaluated at high altitude (10,200 feet) and,
      in conjunction with the Ascensia MICROLET VACULANCE (Bayer), for use with samples
      obtained from four alternative anatomical sites. RESULTS: When the system was
      used with blood from fingersticks, both lay users and HCPs obtained results that
      fulfilled the International Organization for Standardization (ISO) 15197:2003
      accuracy criteria, which advocate that 95% of BG measurements should fall within
      +/-15 mg/dL (for BG concentrations <75 mg/dL) or +/-20% (for BG concentrations >
      or = 75 mg/dL) of the laboratory value. Lay users obtained 96.9% of glucose
      results, and HCPs obtained 96.4% of glucose results, within ISO accuracy
      criteria. People with diabetes who had no prior experience using the system also
      obtained acceptable results (97.0%), as did the HCP using fingerstick samples
      from subjects in the high altitude study (97.0%). Among the alternative
      anatomical sites tested, only the results from the palm met the ISO criteria
      (97.5%), although the results from all four sites (palm, thigh, abdomen, and
      forearm) were clinically acceptable when assessed using error grid analysis. Most
      subjects rated the BGMS as either excellent or very good in a questionnaire, and
      were able to use it properly without training. CONCLUSIONS: These findings
      indicate that the Ascensia CONTOUR System, which does not require calibration by
      the user, is a convenient and accurate instrument with useful features for people
      who routinely monitor BG.

PMID- 15857231
TI  - Analysis: the evolution of glucose meters.

PMID- 15857232
TI  - AKA-Glucose: a program for kinetic and epidemiological analysis of frequently
      sampled intravenous glucose tolerance test data using database technology.
AB  - BACKGROUND: The Bergman Minimal Model enables estimation of two key indices of
      glucose/ insulin dynamics: glucose effectiveness and insulin sensitivity. METHODS
      AND RESULTS: In this paper we describe AKA-Glucose, a program that combines
      MINMOD Millennium (minimal model analysis software) with relational database
      technologies. AKA-Glucose enables the fitting of individual frequently sampled
      intravenous glucose tolerance test (FSIGT) data sets to the Minimal Model and the
      secure storage in a dedicated database (and retrieval from) of thousands of
      individual subjects' demographic data, their individual FSIGT data, and each
      subject's parameters and indices derived from minimal model analysis. AKA-Glucose
      also enables the population analysis of various strata or subpopulations within
      the database. AKA-Glucose has all of the capabilities of MINMOD Millennium,
      provides Minimal Model parameter estimates that are concordant with estimates
      from previous MINMOD software, and allows importation of data files from earlier
      versions of the MINMOD software. CONCLUSIONS: By combining FSIGT data fitting,
      population analysis, and relational database technologies, AKA-Glucose is the
      first minimal model software designed specifically for researchers confronted
      with minimal model and epidemiological analysis of large numbers of either human
      or animal FSIGT data sets.

PMID- 15857233
TI  - Memory of insulin pumps and their record as a source of information about insulin
      therapy in children and adolescents with type 1 diabetes.
AB  - BACKGROUND: This study was designed to provide information regarding basal and
      bolus insulin dosage in children and adolescents using continuous subcutaneous
      insulin infusion (CSII) and to evaluate the safety and efficacy of the CSII
      method in youths. PATIENTS AND METHODS: Data from 100 patients (1.6-18 years old)
      were collected during scheduled visits in an outpatient clinic. The mean duration
      of diabetes was 4.57 years (range 0.6-16 years), and mean duration of CSII
      therapy was 1.75 years (range 0.5-3.0 years). Each child had his or her insulin
      doses reviewed using the Medtronic MiniMed (Northridge, CA) Pumps&Meters software
      program. At each visit glycosylated hemoglobin (HbA1c) values and growth
      parameters (weight and height) were assessed, and episodes of severe hypoglycemia
      and ketoacidosis were recorded. RESULTS: The mean HbA1c value in our study group
      was 7.63 +/- 0.09% (range, 5.15-12.5%). Statistically significant better
      metabolic control was found in children under 10 years of age, in children with
      lower body mass index (r = 0.33), in patients with a lower contribution of basal
      insulin to the total daily dose (r = 0.35; P < 0.05), and in boys. Ten percent of
      participants skipped mealtime boluses, which correlated with their glycemic
      control; in those children HbA1c was 8.67 +/- 0.57% (r = 0.34; P < 0.05). The
      mean total daily insulin was 0.79 +/- 0.02 U/kg/day (range, 0.3-2.0 U/kg/day).
      Basal insulin constituted on average 35.6 +/- 1.1% (5-70%) of the daily insulin
      dose. We found a statistically significant higher contribution of basal insulin
      dose in patients who missed mealtime boluses (r = 0.42; P < 0.05) and a
      significantly lower contribution in pre-pubertal children and in boys (P < 0.05).
      Around 7% of patients made mistakes in programming the basal insulin.
      CONCLUSIONS: CSII may be safely and efficiently used in children with type 1
      diabetes in different age groups. This method of treatment requires regular
      visits to an outpatient clinic, proper education, and frequent revisions of the
      pump's memory.

PMID- 15857234
TI  - The use of two continuous glucose sensors during and after surgery.
AB  - BACKGROUND: Maintaining plasma glucose between 80 and 120 mg/dL is beneficial for
      patients admitted to a surgical intensive care unit, but requires frequent
      glucose monitoring to ensure adequacy of treatment and detection of hypoglycemia.
      We examined whether continuous glucose sensing is feasible and reliable during
      and after major surgical procedures using two commercially available sensors.
      METHODS: Eight patients undergoing abdominal surgery were studied. A CGMS device
      (Medtronic MiniMed, Northridge, CA) and a GlucoDay device (A. Menarini
      Diagnostics, Florence, Italy) were placed in the shoulder region, and a second
      GlucoDay device was placed in the upper leg. Blood glucose was measured every 15
      min for a total duration of 12 h. RESULTS: Technical failure of the CGMS was
      observed peroperatively more frequently than postoperatively (66% of all time
      points vs. 18%, P < 0.001). Technical failure of the GlucoDay device occurred
      most frequently in the GlucoDay placed in the upper leg (64% vs. 17%, P < 0.001).
      Accuracy of all three sensors was comparable peroperatively (74%, 76%, and 63% of
      values in Zone A of the Clarke error grid for the CGMS, GlucoDay shoulder, and
      GlucoDay upper leg, respectively, P = 0.2). Postoperatively, better accuracy was
      observed in both sensors placed in the shoulder compared with the GlucoDay placed
      in the upper leg (73%, 69%, and 51% of values in Zone A for the CGMS, GlucoDay
      shoulder, and GlucoDay upper leg, respectively, P < 0.001). CONCLUSIONS:
      Technical performance and accuracy of continuous glucose sensors need improvement
      before continuous glucose sensors can be used to monitor strict glycemic control
      during and after surgery.

PMID- 15857236
TI  - Systemic diabetes mellitus.

PMID- 15857235
TI  - A computational model to define the molecular causes of type 2 diabetes mellitus.
AB  - BACKGROUND: Metabolic abnormalities associated with type 2 diabetes mellitus
      (DM2) are caused in part by inadequate insulin action and resulting changes in
      gene expression in the skeletal muscle. Two recent, independent studies of human
      skeletal muscle biopsies from ethnically diverse DM2 patients have identified
      coordinated reductions in the expression of the oxidative phosphorylation
      (OXPHOS) genes. Whether these reductions are a consequence or a cause of impaired
      insulin sensitivity remains an open question. METHODS: To address this question
      and to define the underlying molecular causes consistent with the expression
      changes reported in the muscle studies, we created a large-scale computable model
      to analyze the molecular actions and effects of insulin on muscle gene
      expression. The model enables computer-aided reasoning using over 210,000
      molecular relationships assembled from the DM2 literature. RESULTS: We integrated
      the data from these muscle biopsy studies into the model and used computer-aided
      causal reasoning to discover mechanisms that can link alterations in OXPHOS genes
      to decreases in glucose transport, insulin signaling, and risk factors associated
      to post-transplant diabetes mellitus. CONCLUSIONS: The emerging hypotheses
      describe biologic effects in DM2 and offer important cues for molecular targeted
      therapy.

PMID- 15857243
TI  - Probabilistic assessment of clone overlaps in DNA fingerprint mapping via a
      priori models.
AB  - We construct a combinatorially exact probability distribution for the problem of
      a priori clone overlap assessment in DNA fingerprint mapping. It is implemented
      as a general enumeration methodology using Bell's exponential polynomials.
      Established computational metrics do not consider the conditional nature of the
      problem. They dramatically overpredict actual match probabilities as a
      consequence. This elevates the rate of false-negative overlap declarations, which
      is consistent with previous validation studies. Increased measurement resolution
      does not significantly improve accuracy. We describe general trends in error
      behavior for intermediate-size DNA clones and discuss corresponding limits on the
      ability to assess certain overlaps.

PMID- 15857244
TI  - A random polymer model of the statistical significance of structure alignment.
AB  - A theory for assessing the statistical significance of structure alignment is
      developed using a random or Gaussian chain model. In this model, we consider the
      statistical distribution of the root mean square distance (rmsd) of the alignment
      between two random chains of equal length and common center of mass (referred to
      as Case 1). We demonstrate that the rmsd2 is distributed as a sum of independent
      Gamma variables. Analytic results on the mean and variance of the rmsd2 are
      presented. Since rmsd is strongly dependent on the length, we define the
      dimensionless quantity, reduced rmsd, as the rmsd divided by the radius of
      gyration. We find that the reduced rmsd can be accurately approximated by an
      extreme value distribution (EVD) that is independent of chain length and of bond
      length. The parameters of the EVD can be calculated from the mean and the
      variance of the rmsd2. We also consider the case of two chains with a common
      center of mass that are then rotated to minimize the rmsd (Case 2). In this case,
      the distribution of reduced rmsd can again be accurately approximated by an EVD,
      which is independent of the chain length and expected bond length. This
      distribution is used to calculate the p-value for a given reduced rmsd.
      Performing an analogous comparison for proteins, we find that <rmsd>
      approximately M(nu) and nu = 0.28 and 0.32 for Case 1 and Case 2, respectively,
      where M is the chain length. This result for Case 2 exactly matches with previous
      scaling results and suggests that rmsd/M(nu)is an appropriate metric for protein
      structure alignment and will be independent of chain length. We also find that
      the new score roughly follows the EVD.

PMID- 15857245
TI  - Finding motifs in promoter regions.
AB  - A central issue in molecular biology is understanding the regulatory mechanisms
      that control gene expression. The availability of whole genome sequences opens
      the way for computational methods to search for the key elements in transcription
      regulation. These include methods for discovering the binding sites of DNA
      binding proteins, such as transcription factors. A common representation of
      transcription factor binding sites is a position specific score matrix (PSSM). We
      developed a probabilistic approach for searching for putative binding sites.
      Given a promoter sequence and a PSSM, we scan the promoter and find the position
      with the maximal score. Then we calculate the probability to get such a maximal
      score or higher on a random promoter. This is the p-value of the putative binding
      site. In this way, we searched for putative binding sites in the upstream
      sequences of Saccharomyces cerevisiae, where some binding sites are known
      (according to the Saccharomyces cerevisiae Promoters Database, SCPD). Our method
      produces either exact p-values, or a better estimate for them than other methods,
      and this improves the results of the search. For each gene we found its
      statistically significant putative binding sites. We measured the rates of true
      positives, by a comparison to the known binding sites, and also compared our
      results to these of MatInspector, a commercially available software that looks
      for putative binding sites in DNA sequences according to PSSMs. Our results were
      significantly better. In contrast with us, MatInspector doesn't calculate the
      exact statistical significance of its results.

PMID- 15857246
TI  - Nonrandom clusters of palindromes in herpesvirus genomes.
AB  - Palindromes are symmetrical words of DNA in the sense that they read exactly the
      same as their reverse complementary sequences. Representing the occurrences of
      palindromes in a DNA molecule as points on the unit interval, the scan statistics
      can be used to identify regions of unusually high concentration of palindromes.
      These regions have been associated with the replication origins on a few
      herpesviruses in previous studies. However, the use of scan statistics requires
      the assumption that the points representing the palindromes are independently and
      uniformly distributed on the unit interval. In this paper, we provide a
      mathematical basis for this assumption by showing that in randomly generated DNA
      sequences, the occurrences of palindromes can be approximated by a Poisson
      process. An easily computable upper bound on the Wasserstein distance between the
      palindrome process and the Poisson process is obtained. This bound is then used
      as a guide to choose an optimal palindrome length in the analysis of a collection
      of 16 herpesvirus genomes. Regions harboring significant palindrome clusters are
      identified and compared to known locations of replication origins. This analysis
      brings out a few interesting extensions of the scan statistics that can help
      formulate an algorithm for more accurate prediction of replication origins.

PMID- 15857247
TI  - Linear regression models for solvent accessibility prediction in proteins.
AB  - The relative solvent accessibility (RSA) of an amino acid residue in a protein
      structure is a real number that represents the solvent exposed surface area of
      this residue in relative terms. The problem of predicting the RSA from the
      primary amino acid sequence can therefore be cast as a regression problem.
      Nevertheless, RSA prediction has so far typically been cast as a classification
      problem. Consequently, various machine learning techniques have been used within
      the classification framework to predict whether a given amino acid exceeds some
      (arbitrary) RSA threshold and would thus be predicted to be "exposed," as opposed
      to "buried." We have recently developed novel methods for RSA prediction using
      nonlinear regression techniques which provide accurate estimates of the real
      valued RSA and outperform classification-based approaches with respect to
      commonly used two-class projections. However, while their performance seems to
      provide a significant improvement over previously published approaches, these
      Neural Network (NN) based methods are computationally expensive to train and
      involve several thousand parameters. In this work, we develop alternative
      regression models for RSA prediction which are computationally much less
      expensive, involve orders-of-magnitude fewer parameters, and are still
      competitive in terms of prediction quality. In particular, we investigate several
      regression models for RSA prediction using linear L1-support vector regression
      (SVR) approaches as well as standard linear least squares (LS) regression. Using
      rigorously derived validation sets of protein structures and extensive cross
      validation analysis, we compare the performance of the SVR with that of LS
      regression and NN-based methods. In particular, we show that the flexibility of
      the SVR (as encoded by metaparameters such as the error insensitivity and the
      error penalization terms) can be very beneficial to optimize the prediction
      accuracy for buried residues. We conclude that the simple and computationally
      much more efficient linear SVR performs comparably to nonlinear models and thus
      can be used in order to facilitate further attempts to design more accurate RSA
      prediction methods, with applications to fold recognition and de novo protein
      structure prediction methods.

PMID- 15857248
TI  - Epigenetic hypothesis tests for methylation and acetylation in a triple
      microarray system.
AB  - To fully elucidate the functional relationship between DNA methylation and
      histone hypoacetylation in gene silencing, we have developed an integrated
      "triple" microarray system that allows us to begin to decipher the influence of
      epigenetic hierarchies on the regulation of gene expression in cancer cells. Our
      hypothesis is that in the promoter region of a silenced gene, reversal of two
      epigenetic factors (i.e., DNA demethylation and/or histone hyperacetylation) is
      highly correlated with gene reexpression after treatment of the human epithelial
      ovarian cancer cell line CP70 with the drug combination 5-aza-2'-deoxycytidine
      (DAC), a demethylating agent, and trichostatin A (TSA), an inhibitor of histone
      deacetylases. To estimate the posterior probabilities for genes with altered
      expression, DNA methylation and histone acetylation status measured with a triple
      microarray system, we have employed an established empirical Bayes model. Two
      methods have been proposed to test our hypothesis that DNA demethylation and
      histone hyperacetylation are highly correlated among those up-regulated genes.
      One method follows a weighted least squares regression, while the other is
      derived from a chi-square statistic. The data derived by these approaches, which
      have been further verified through bootstrap analyses, support the proposed
      epigenetic correlation (p-values are less than 0.001). Further simulations
      suggest that even if the constant variance and normality assumptions do not hold,
      the power of those two tests is robust.

PMID- 15857250
TI  - Telethinking.

PMID- 15857251
TI  - Innovative programs in telemedicine.

PMID- 15857252
TI  - The use of telemedicine for delivering continuing medical education in rural
      communities.
AB  - Physicians in rural communities have limited access to continuing medical
      education (CME) opportunities. We hypothesized that CME could be delivered via a
      telemedicine network as effectively as in-person. Our institution delivers CME
      lectures and grand rounds in Burlington, Vermont, for in-person attendees, and
      also via a telemedicine network that links 14 hospitals in Vermont and rural
      northeastern New York. All participants complete an evaluation questionnaire to
      receive CME credit. We compared the questionnaire responses of those attending in
      person with those attending via the telemedicine network. From October 1, 2000 to
      June 30, 2003, there were 4733 CME sessions, 650 of which had both in-person and
      telemedicine attendees. Responses from these 650 sessions were compared. Most
      questions relating to lecture quality scored higher for in-person attendees.
      Compared to having the presenter in the room, telemedicine attendance was judged
      to be "more effective" in 19% (n = 334), "as effective" in 60%, (n = 1074), and
      "less effective" in 21% (n = 367). Eighteen percent of telemedicine attendees
      said they would have traveled to attend the session. Telemedicine-delivered CME
      was considered at least as effective as in-person CME 79% of the time. Travel was
      avoided for 18% of the remote attendees. CME was delivered where it would not
      have been obtained for 82% of the remote attendees. Telemedicine systems can be
      used to deliver CME, in spite of lower overall ratings compared to in-person
      attendance.

PMID- 15857253
TI  - Acquisition and evaluation of radiography images by digital camera.
AB  - To determine applicability of low-cost digital imaging for different radiographic
      modalities used in consultations from remote areas of the Ecuadorian rainforest
      with limited resources, both medical and financial. Low-cost digital imaging,
      consisting of hand-held digital cameras, was used for image capture at a remote
      location. Diagnostic radiographic images were captured in Ecuador by digital
      camera and transmitted to a password-protected File Transfer Protocol (FTP)
      server at VCU Medical Center in Richmond, Virginia, using standard Internet
      connectivity with standard security. After capture and subsequent transfer of
      images via low-bandwidth Internet connections, attending radiologists in the
      United States compared diagnoses to those from Ecuador to evaluate quality of
      image transfer. Corroborative diagnoses were obtained with the digital camera
      images for greater than 90% of the plain film and computed tomography studies.
      Ultrasound (U/S) studies demonstrated only 56% corroboration. Images of
      radiographs captured utilizing commercially available digital cameras can provide
      quality sufficient for expert consultation for many plain film studies for
      remote, underserved areas without access to advanced modalities.

PMID- 15857254
TI  - The essence of telehealth readiness in rural communities: an organizational
      perspective.
AB  - This paper examines telehealth readiness from an organizational perspective and
      explores the essence of telehealth readiness among four domains, namely,
      patients, practitioners, the public, and organizations in rural Canadian
      communities. Because readiness is a necessary requirement for the successful
      implementation of an innovation, it is important to identify and ensure core
      factors of readiness before costly investments are made. The findings presented
      here derive from a qualitative phenomenological research approach involving
      semistructured telephone interviews with four key informants (respondents). The
      data identified four categories of readiness in an organizational setting: core
      readiness, engagement, structural readiness, and nonreadiness. Understanding
      organizational readiness within rural and remote communities is an important step
      for the successful implementation of telehealth services into existing systems of
      health care.

PMID- 15857255
TI  - Electronic health records within integrated care in Germany.
AB  - The planned introduction of an electronic health card is seen as a milestone in
      the dissemination of extended electronic health records in Germany. This paper
      deals with the main issues likely to result from the use of the electronic health
      insurance card. The role of the patient in the health care process and the
      patients enhanced access to his or her personal medical record are reflected. A
      high level of acceptance of the electronic health insurance card and extended
      electronic documentation procedures can be expected if ethical, legal, and
      technological concerns of the public are addressed and appropriate incentives are
      established. Finally, the electronic health insurance card can serve as a useful
      aid to support the ongoing implementation of disease management programs for the
      most important chronic conditions in Germany.

PMID- 15857256
TI  - Skill sets for the home telehealth practitioner: a recipe for success.
AB  - Successful implementation of home telehealth programs require unique skills and
      personality traits of professionals driving the program. Understanding these
      traits and skills, and how they predict performance will help staff recognize
      superior applicants when recruiting individuals for such positions. An extensive
      literature review ties research published on human factors, what they are, the
      role they play in performance, and how this may translate into a successful
      telehealth program. We compared case examples of some successful home telehealth
      programs. Furthermore, a summary of problems approached and resolved by the home
      telehealth professionals illustrated decision making and action steps taken that
      correlated to research published on human factors. Further research is needed to
      validate the tools used by other fields of study to select and identify
      successful individuals.

PMID- 15857265
TI  - Report from the CDC: Evaluability assessment of the rape prevention and education
      program: summary of findings and recommendations.
AB  - This paper describes an evaluability assessment of CDC's Rape Prevention and
      Education (RPE) Program conducted to establish a baseline description and
      understanding of the current activities and goals of the program, revisit and
      update program performance measures, and identify opportunities for CDC to
      provide training and technical assistance to states. Data were collected using
      (1) a web-based survey of all state and territory health departments, other
      government agencies involved in the administration of the program, and sexual
      assault coalitions, (2) in-depth interviews with the same respondents during site
      visits to a sample of 14 states, and (3) focus groups in 5 of these states with
      local providers. This paper highlights the findings and summarizes
      recommendations to improve the program. It concludes with examples of steps CDC
      is taking to implement the recommendations.

PMID- 15857266
TI  - Toward optimal health: William P. Docken, M.D. and David S. Pisetsky, M.D., Ph.D.
      discuss arthritis in women. Interview by Jody R. Godfrey.

PMID- 15857267
TI  - Sexual minority women's coping and psychological adjustment after a diagnosis of
      breast cancer.
AB  - OBJECTIVE: To determine factors that influence sexual minority women's coping
      responses and adjustment to breast cancer. METHODS: We conducted a cross
      sectional study with 64 sexual minority women with breast cancer who were
      recruited through targeted community-based sampling. In this study, sexual
      minority women consisted of three sexual orientation groups: those who self
      reported partnering with women and those with a lesbian or bisexual identity. We
      determined the number of years of sexual minority status and disclosure of sexual
      orientation and used standardized measures to assess these women's coping and
      adjustment to breast cancer. Data were analyzed using statistical methods as
      appropriate for the level of data. RESULTS: We determined that sexual minority
      factors, such as sexual orientation group, influenced coping and adjustment even
      after illness and social support factors were controlled. In multivariate
      analyses, women who identified as lesbians or bisexuals used less maladaptive
      coping compared with women who reported partnering with women. The association
      between reporting a lesbian identity and lower distress approached significance
      in multivariate regression equations. CONCLUSIONS: Of the sexual minority factors
      that were considered, sexual orientation group, number of years of sexual
      minority status, and disclosure of sexual minority status, only sexual
      orientation group was related to coping and lower distress. Contrary to
      expectations, disclosure of sexual orientation did not relate to coping and lower
      distress. The findings support the need for future studies to include different
      aspects of sexual minority status, in particular, clearly defined sexual
      orientation groups.

PMID- 15857268
TI  - Depression among female family planning patients: prevalence, risk factors, and
      use of mental health services.
AB  - BACKGROUND: Depression is a common, yet underdiagnosed mental health problem
      among women of reproductive age. Whereas risk factors and treatment of depression
      have been well studied among women of all ages, little attention has been paid to
      the prevalence of depression and clinical outcomes of clinical depressive
      symptoms among women who visit public family planning clinics. METHODS: A total
      of 588 female patients of three North Carolina health department family planning
      clinics were screened for their depressive symptoms. Women who screened positive
      for depressive symptoms during the initial assessment were referred for further
      mental health evaluation and treatment. Multivariate logistic regression was
      performed to examine risk factors of depressive symptoms, and a flow chart was
      used to demonstrate referral process and outcomes. RESULTS: Approximately half of
      the women in the study evidenced high levels of depressive symptoms that were
      consistent with having a clinically relevant mental health problem. Results from
      multivariate analysis found that being classified as currently depressed was
      significantly associated with previous treatment for depression (OR = 5.43), no
      social support (OR = 3.57), and unemployment (OR = 3.21). Caucasians were
      significantly more likely than African Americans to be depressed (OR = 2.63), and
      teenagers and women with low levels of education were more likely to evidence
      depression (OR = 1.99 and OR = 1.78, respectively). Few of the patients who were
      classified as depressed and were referred for further mental health evaluation
      followed through with the referrals. CONCLUSIONS: These findings underscore the
      importance of providing routine screening of women for depression within the
      context of family planning services and providing referrals, follow-up, and
      mental health treatment to those women in need.

PMID- 15857269
TI  - Influence of cardiorespiratory fitness on the association between C-reactive
      protein and metabolic syndrome prevalence in racially diverse women.
AB  - BACKGROUND: Metabolic syndrome and C-reactive protein (CRP) are independent
      predictors of cardiovascular disease (CVD) among women. The extent to which
      cardiorespiratory fitness influences the relationship between CRP and metabolic
      syndrome is unknown. METHODS AND RESULTS: Cross-sectional associations among
      fitness, CRP, and metabolic syndrome were examined in 135 African American,
      Native American, and Caucasian women (55 +/- 11 years, 28 +/- 6 kg/m2). Fitness
      was quantified with a symptom-limited maximal treadmill exercise test. Plasma CRP
      concentrations were determined with the Dade-Behring high-sensitivity
      immunoassay. Metabolic syndrome was defined according to NCEP-ATP III. Metabolic
      syndrome, CRP, and fitness varied (p < 0.05) by race. Race-adjusted CRP values
      were directly associated (p < 0.05) with each metabolic syndrome component. After
      adjusting for age and race, the relative odds of metabolic syndrome was 3.6 (95%
      CI = 1.5 - 8.4) in women with elevated (> 2.0 mg/L) vs. low CRP. Adjustment for
      smoking, hormone therapy, body mass index (BMI), and HOMA insulin resistance did
      not eliminate this association (p < 0.05). The association between CRP and the
      metabolic syndrome was no longer significant (OR = 1.3, 95% CI = 0.9 - 5.9, p =
      0.59) after adjustment for fitness. CONCLUSIONS: Higher cardiorespiratory fitness
      may be an important consideration in the milieu of vascular inflammation and
      metabolic syndrome.

PMID- 15857270
TI  - Defining low risk for coronary heart disease among women with chest pain
      syndrome: a prospective evaluation.
AB  - BACKGROUND: A better understanding of the clinical manifestations of coronary
      disease in women may lead to earlier recognition and better outcomes. METHODS:
      One hundred fifty-eight women coming to primary care physicians, emergency rooms,
      or cardiology clinics with undefined chest pain and at least two risk factors
      underwent detailed clinical evaluation of risk factor profile and symptom
      characteristics as well as stress testing. The significance of the presenting
      symptoms was evaluated on the basis of clinical events during an average 26.2
      months of follow-up. Noncardiac pain was diagnosed on the basis of spontaneous
      resolution of symptoms, establishment of an alternative diagnosis, or negative
      coronary angiography. Cardiac chest pain was established by the development of
      cardiac clinical events or angiographic demonstration of coronary disease.
      RESULTS: Noncardiac chest pain was established in 128 (81%) patients. The
      remaining 30 (19%) either were found to have had cardiac chest pain or remain
      symptomatic without definitive diagnosis. Multivariate analysis revealed that
      noncardiac chest pain was best predicted by a combination of nondiabetic status
      and negative stress testing. The clinical characteristics of the chest pain
      syndrome were not significant contributors. CONCLUSIONS: In nondiabetic women
      with chest pain syndrome and at least two other cardiac risk factors, a negative
      stress test predicts a benign course in over 2 years of follow-up.

PMID- 15857271
TI  - A comparison of recalled date of last menstrual period with prospectively
      recorded dates.
AB  - BACKGROUND: Women are often asked to recall the first day of their last menstrual
      period (LMP date) in a clinic setting (i.e., pregnancy dating, x-rays). There are
      no data supporting the validity of these reports. METHODS: Using data from a
      group of 385 women ages 35-49 from a larger cohort study in the Washington, DC,
      area, we constructed menstrual segments from a prospective daily menstrual
      record. We then compared the first day of a menstrual segment to a woman's
      recalled LMP date at a subsequent study-related clinic appointment to assess the
      accuracy of recall. RESULTS: More than half of the women (56%) accurately
      recalled their LMP date; 74% were within 1 day, and 81% were within 2 days. Women
      tended to underreport (25%) the length of time since their last menstrual period
      rather than overreport the length of time (19%). Recall accuracy did not vary
      significantly with education or by whether the woman usually recorded her
      menstrual cycle when not in the study. As one might expect, women with a shorter
      recall duration tended to report more accurately. DISCUSSION: Women appear to
      recall their LMP dates fairly accurately, but inaccurate recall was not random.
      When length of recall was 3 weeks or longer, women tended to overestimate the
      time since LMP. This suggests that gestational age calculated from LMP date will
      tend to be overestimated. Most women can recall the date of their LMP reasonably
      well regardless of their education and whether they usually record their LMP
      dates.

PMID- 15857272
TI  - Effects of including soy protein in a blood cholesterol-lowering diet on markers
      of cardiac risk in men and in postmenopausal women with and without hormone
      replacement therapy.
AB  - BACKGROUND: Increased consumption of soy foods has been associated with reduction
      in low density lipoprotein cholesterol (LDL-C) in both clinical and observational
      studies. However, it is not clear whether adding soy to a low-fat diet has
      additional lipid-lowering benefits, and few previous studies have examined these
      effects in women using hormone replacement therapy (HRT+). METHODS: We tested
      whether adding soy protein to a low-fat, high-fiber, Step I diet improved cardiac
      risk markers in 18 postmenopausal women and 14 men with hypercholesterolemia and
      examined whether concurrent use of HRT altered diet responsiveness. Diets were
      matched for macronutrient content, and all food was provided. After 3 weeks on
      the Step I diet, subjects were randomized to diets (6 weeks) containing 25 g/day
      protein isolate from soy or cow's milk, with crossover. The soy treatment
      contained 90 mg/day isoflavones. Lipids, vascular cell adhesion molecule-1 (VCAM
      1), p-selectin, and urinary isoflavonoids were measured at the end of each diet.
      RESULTS: In men and HRT- women only, there were significant reductions in LDL-C (
      17.3%), high-density lipoprotein cholesterol (HDL-C) (-15.3%), and triglycerides
      (-11.5%) during the Step I diet, and soy had no additional effects. At study
      entry, HRT+ women had lower LDL-C and higher triglycerides than men. Their LDL-C
      was unchanged, and triglycerides were significantly reduced (-15.1%) by the Step
      I diets. Isoflavonoid excretion was unrelated to diet response or HRT status.
      CONCLUSIONS: In men and HRT- women, the diets significantly lowered LDL-C,
      independent of soy intake. In HRT+ women, the diets improved triglycerides
      without lowering HDL-C.

PMID- 15857273
TI  - The management of asthma and rhinitis during pregnancy.
AB  - Asthma and rhinitis frequently complicate pregnancy. The course of asthma may be
      adversely altered by gestation, placing the mother and fetus at risk. Therefore,
      pregnant patients with persistent asthma require an aggressive asthma management
      plan that includes environmental control measures and the use of long-term
      controller medications. Inhaled corticosteroids (ICSs) are the preferred long
      term controller medication for persistent asthma, based on efficacy. However,
      safety concerns regarding corticosteroids may cause physicians or patients to
      seek an alternate, less effective treatment during pregnancy. The Food and Drug
      Administration's pregnancy category ratings are based on animal and human safety
      data. Because ICSs were previously rated pregnancy category C (i.e., with human
      studies lacking and animal studies either lacking or positive for fetal risk),
      other asthma controllers, such as cromolyn and nedocromil, that carry a pregnancy
      category B rating (i.e., showing no evidence of fetal risk in humans or animal
      studies negative for fetal risk) appeared to be more desirable for use during
      pregnancy. One ICS, budesonide, was reclassified as pregnancy category B based on
      human data supporting its use during pregnancy. In moderate and severe persistent
      asthma, add-on therapy may be considered, including long-acting beta2-adrenergic
      agonists, leukotriene receptor antagonists, and theophylline. Because rhinitis
      may adversely affect quality of life and the course of asthma, recommendations
      for aggressive management also apply.

PMID- 15857275
TI  - Effects of pyrrolidine dithiocarbamate, an NF-kappaB inhibitor, on cytokine
      expression and ocular inflammation in experimental autoimmune anterior uveitis.
AB  - AIMS: The aim of this study was to investigate the effects of pyrrolidine
      dithiocarbamate (PDTC), a nuclear factor (NF)-kappaB inhibitor, on cytokine
      expression and suppression of anterior chamber inflammation in experimental
      autoimmune anterior uveitis. Uveitis was induced in the Lewis rats with the
      injection of a melanin-associated antigen into the peritoneum and footpad. At
      defined time points, cytokine mRNA expressions in the iris and ciliary body were
      measured by using a semiquantitative polymerase chain-reaction method. RESULTS:
      We found that interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF)-alpha
      mRNA expression peaked during the active phase of uveitis, whereas interleukin
      (IL)-10 mRNA increased during the disease resolution. In a separate experiment,
      PDTC (100 and 200 mg/kg/day) was administrated intraperitoneally daily after
      immunization. We found that PDTC (100 and 200 mg/kg/day) effectively suppressed
      ocular inflammation, as indicated by reduced clinical scores and inflammatory
      cells infiltration in aqueous humor and the iris and ciliary body. CONCLUSIONS:
      The inhibitory effects of PDTC are mainly resulted from inhibiting the expression
      of proinflammatory cytokines, TNF-alpha and IFN-gamma but augmenting anti
      inflammatory cytokines, IL-10 expression. These findings suggest that the
      application of NF-kappaB inhibitors may be a potential therapeutic method for the
      treatment of acute anterior uveitis.

PMID- 15857276
TI  - Genistein inhibited retinal neovascularization and expression of vascular
      endothelial growth factor and hypoxia inducible factor 1alpha in a mouse model of
      oxygen-induced retinopathy.
AB  - The effects of genistein on neovascularization, vascular endothelial growth
      factor (VEGF), and hypoxia inducible factor 1alpha (HIF1alpha) protein expression
      in a mouse model of oxygen-induced retinopathy were studied. The model of oxygen
      induced retinal neovascularization was induced in newborn C57BL/6 mice by
      exposing 7-day-old mice to 75% oxygen for 5 days and then housing them in room
      air (relative hypoxia). Retinopathy was assessed by quantitation of vascular cell
      nuclei anterior to inner limiting membrane. Judged by relative fluorescence using
      a confocal scanning laser microscope coupled to a computer, VEGF and HIF1alpha
      protein expression were investigated. Genistein markedly inhibited the numbers of
      nuclei protruding above the inner limiting membrane under relative hypoxia
      conditions. The levels of nuclei numbers were suppressed by 50, 100, and 200
      mg/kg body weight /day genistein to 87.4%, 72.0%, and 59.4%, respectively,
      compared to that untreated with genistein. VEGF protein was constitutively
      expressed in the preretinal area under normoxia conditions. Genistein markedly
      inhibited relative-hypoxia-elicited VEGF expression elevation in a dose-dependent
      manner. HIF1alpha expression was also observed in normoxia conditions. There was
      a 2.4-fold induction in preretinal HIF1alpha expression in oxygen-reared animals
      when compared to room-air-reared animals. Genistein dose-dependently suppressed
      HIF1alpha protein expression. These results indicated that the inhibition of VEGF
      and HIF1alpha protein expression by genistein may partly account for its effect
      on retinal neovascularization in vivo, and genistein could be an effective agent
      in the prevention and treatment of ocular neovascularization.

PMID- 15857277
TI  - Inhibition of cyclooxygenase 2 synthesis suppresses Herpes simplex virus type 1
      reactivation.
AB  - Recurrent herpes virus infection, in which the virus reactivates from the nervous
      system and causes painful lesions in peripheral tissues, is a significant
      clinical problem. Our recent studies showing that the amount of cyclooxygenase 2
      (COX-2) in the trigeminal ganglia of heat-stressed untreated mice is higher than
      the amount in heat-stressed mice treated with the COX-2 inhibitor, celecoxib,
      have indicated that the prostaglandin synthesis pathway--and in particular COX-2-
      may be an intermediate in the pathway to herpes viral reactivation. To further
      study this process, we infected the corneas of mice using topical application to
      a lightly scratched epithelium and waited 30 days for Herpes simplex virus type 1
      (HSV-1) latency to be established in the trigeminal ganglia. Prior to the
      induction of viral reactivation, the mice were treated orally with celecoxib.
      Treated and untreated mice were induced to undergo reactivation by immersion in
      43 degrees C water for 10 min. The shedding of virus at the ocular surface was
      determined by culturing ocular swabs with indicator cells. The presence of
      infectious virus in the trigeminal ganglion was evaluated by incubating ganglion
      homogenates with indicator cells and observing for cytopathic effect. Celecoxib
      treatment significantly suppressed viral reactivation when given prophylactically
      by the gastrointestinal route. The numbers of corneas and ganglia containing
      infectious virus were significantly lower in the celecoxib-treated animals,
      compared to the placebo-treated mice. These experiments demonstrate that a
      selective COX-2 inhibitor can suppress hyperthermic stress-induced herpes viral
      reactivation in the nervous system. It may be possible to use COX-2 inhibitors to
      prevent viral reactivation in high-risk patients by drug prophylaxis.

PMID- 15857278
TI  - Ocular hypotensive DP-class prostaglandin receptor affinities determined by
      quantitative autoradiography on human eye sections.
AB  - The aim of this study was to define the localization and pharmacology of DP
      prostaglandin receptors in human eye sections using a novel DP-antagonist
      radioligand ([3H]-BWA868C), using various intraocular pressure (IOP)-lowering DP
      prostaglandins and the technique of quantitative autoradiography on 20-microm
      sections of frozen human eyes. [3H]BWA868C yielded well-defined autoradiograms of
      DP-receptors in human eyes with up to 82% specific binding. High densities of DP
      receptors were associated with the ciliary epithelium/process, iris, choroid,
      longitudinal and circular ciliary muscles, and retina. Low specific binding was
      observed in the lens and cornea. The DP-receptor agonists, BW245C (Ki = 4-8 nM),
      SQ27986 (Ki = 6-9 nM), ZK118182 (Ki = 12-33 nM), 3,4-dihydro-ZK118182 (AL-6556;
      Ki = 1.6-4.3 (microM) and 3,4-dihydro-ZK118182 isopropyl ester (AL-6598; Ki = 2.9
      9.7 microM), exhibited varying affinities for human DP-receptors in the ciliary
      process, longitudinal and circular ciliary muscles, and iris, respectively. These
      human ocular tissue affinity values correlated well with nonocular tissue
      affinities and functional potencies of these prostaglandins in cultured cells (r
      = 0.93-0.99). In conclusion, these quantitative autoradiographic studies revealed
      a high density of DP-prostaglandin receptors in human ciliary muscles, ciliary
      process, and iris, indicating that this class of prostaglandin may lower IOP by
      uveoscleral pathway and also by inhibiting aqueous humor production. The
      pharmacological attributes of [3H]BWA868C-labeled receptor sites studied using in
      situ quantitative autoradiography matched those previously documented for several
      other DP-receptor-containing cells and tissues.

PMID- 15857279
TI  - Effects of daunorubicin and CD95L on retinal function in superfused vertebrate
      retina.
AB  - Alternative treatments of proliferative vitreoretinopathy (PVR) are needed. The
      intravitreal application of daunorubicin combined with CD95 ligand (CD95L) could
      provide a new therapeutic strategy. The effects of this application on bovine
      retinal function were investigated. Bovine retina preparations were perfused with
      a standard solution preequilibrated with oxygen. The b-wave and, after the
      addition of aspartate, the photoreceptor potential P III of the electroretinogram
      (ERG) were recorded using Ag/AgCl electrodes. Stable ERG amplitudes were
      recorded, then daunorubicin was added to the solution for 45 minutes, also with
      the addition of CD95L antibody. Subsequently, the preparation was reperfused with
      the standard solution for 100 minutes, to allow for recovery. The reduction in b
      wave amplitude was reversible and not significantly changed by the addition of
      0.25 microg/mL CD95L antibody to 13 microM of daunorubicin. The reduction of the
      b-wave amplitude was significantly changed and only partly reversible within the
      recovery time using 40 microM and 80 microM of daunorubicin. The photoreceptor
      potential P III amplitude was not significantly changed for up to 80 microM of
      daunorubicin. The ERG showed toxic effects of daunorubicin above a concentration
      of 13 microM used therapeutically in humans. The combination with CD95L did not
      increase retinal toxicity. It is, therefore, concluded that daunorubicin may be
      applied intraocularly, combined with CD95L, without interfering with retinal
      function.

PMID- 15857280
TI  - Preservation of tear film integrity and inhibition of corneal injury by
      dexamethasone in a rabbit model of lacrimal gland inflammation-induced dry eye.
AB  - PURPOSE: The aim of this study was to establish a clinically relevant short-term
      animal model of dry eye with utility in identifying compounds with potential
      therapeutic efficacy. METHODS: Rabbit lacrimal glands were injected with the T
      cell mitogen Concanavalin A (Con A) and inflammation, tear function, and corneal
      epithelial cell integrity were subsequently assessed. The inflammatory response
      was characterized by quantifying biochemical markers of inflammation ex vivo and
      by confirming inflammatory cell influx by histology. Matrix metalloproteinase-9
      (MMP-9) and proinflammatory cytokines IL-1beta, IL-8, and TGF-beta1 were
      quantified in tissue extracts. Tear function was monitored by measuring tear
      fluorescein clearance and tear breakup time (TBUT). Corneal epithelial cell
      integrity was determined by quantifying the uptake of methylene blue dye
      following the exposure of rabbits to a low-humidity environment. The anti
      inflammatory corticosteroid, dexamethasone, was administered topically as
      indicated for each study. RESULTS: Histopathologic evaluation of lacrimal glands
      injected with Con A revealed a pronounced inflammatory process characterized by
      lymphocytic infiltration, multifocal necrosis, and fibroplasia. Elevated levels
      of MMP-9 and cytokines IL-1beta, IL-8, and TGF-beta1 were detected in the
      lacrimal gland and cornea. Inflammation of the rabbit lacrimal gland following an
      injection of Con A significantly reduced tear clearance and TBUT and increased
      susceptibility to desiccation-induced corneal damage. Dexamethasone was
      prophylactically and therapeutically effective in this inflammation model of dry
      eye, restoring tear function and inhibiting corneal injury following topical
      ocular application. CONCLUSIONS: Characteristics of this rabbit lacrimal gland
      inflammation model of dry eye are consistent with the current understanding of
      dry eye as a local ocular surface inflammatory response to abnormal tear volume
      and composition. These results suggest that this rabbit model of dry eye may be
      employed to assess the therapeutic efficacy of mechanistically diverse agents on
      clinically relevant signs of ocular surface disease. These methods were
      strategically developed to be applicable for advancing drug discovery for a broad
      spectrum of dry eye patients.

PMID- 15857281
TI  - Toxicological evaluation of micafungin ophthalmic solution in rabbit eyes.
AB  - There have been no reports of the topical application of micafungin to the eye.
      The aim of this study was to evaluate the safety of topical instillation of 0.1%
      micafungin ophthalmic solution in rabbit eyes. In New Zealand white rabbits (n =
      6), 50 microL of 0.1% micafungin solution was topically instilled to 1 eye, and
      50 microL of sterile saline was applied to the other eye. Both eyedrops were
      administered hourly from 7 A.M. for 7 days. Measurements were conducted on
      corneal thickness, intraocular pressure, endothelial cell density, and lactate
      dehydrogenase (LDH) activity of tear samples. The eyes were examined slit-lamp
      biomicroscopically and histopathologically. Topical micafungin application for 1
      week did not induce any changes in intraocular pressure, endothelial cell
      density, and tear LDH. Corneal thickness after instillation was slightly, but
      significantly, smaller in the micafungin group than in the control group (P =
      0.0156, paired t test), but this difference disappeared within 24 hours after the
      final instillation. Biomicroscopy and histopathology revealed no significant
      toxic influence of micafungin application on the cornea. Topical instillation of
      micafungin solution had no apparent toxicity to the cornea. These results warrant
      future studies on the efficacy of micafungin ophthalmic solution against corneal
      fungal infection.

PMID- 15857282
TI  - Tolerability and efficacy of N-chlorotaurine in epidemic keratoconjunctivitis--a
      double-blind, randomized, phase-2 clinical trial.
AB  - The aim of this study was to assess the tolerability and efficacy of N
      chlorotaurine (NCT), an endogenous antimicrobial agent, in epidemic
      keratoconjunctivitis. In a prospective double-blind, randomized phase 2b study,
      the infected eyes were treated for 7 days with eye drops containing 1% aqueous
      solution of N-chlorotaurine (33 subjects) or gentamicin (27 subjects, control
      group). Adenovirus types 3, 4, 8, 19, and 37 were detected in 39 subjects (65%),
      enteroviruses in 8 (13.3%), and staphylococci in 5 (8.3%). Subjective and
      objective symptoms were scaled and added to a subjective and objective score,
      respectively, on day 1 (baseline), day 4, and day 8. Analyzing the whole study
      population, the subjective score on day 8 was lower in the NCT group (P = 0.016),
      whereas there were no differences in the objective score. However, in severe
      infections caused by adenovirus type 8 (n = 20) both the subjective and objective
      score were lower in the NCT group on day 4 (P = 0.003 and 0.015, respectively),
      which was also true for the subjective score on day 8 (P = 0.004) in this
      subgroup. The frequency of subepithelial infiltrates was similar in both groups.
      N-chlorotaurine was well-tolerated, shortened the duration of illness, and seems
      to be a useful causative therapeutic approach in severe epidemic
      keratoconjunctivitis.

PMID- 15857283
TI  - Corneal endothelial deposits associated with rifabutin use.
AB  - PURPOSE: The aim of this study was to report on the possible development of
      corneal endothelial deposits resulting from the use of rifabutin. METHODS: Case
      series consisting of 3 patients treated with rifabutin were retrospectively
      studied. Two of the patients were infected with human immunodeficiency virus. A
      corneal and external disease specialist performed a complete ophthalmologic exam
      and obtained medical histories of the patients. RESULTS: All cases developed
      corneal endothelial deposits after previous use of rifabutin. The deposits were
      bilateral, yellow-white colored, stellate, and mainly peripheral. CONCLUSIONS: In
      these 3 cases, the unique positive ocular finding was corneal endothelial
      deposits, which may be related to the use of rifabutin.

PMID- 15857284
TI  - The efficacy and safety of topical brinzolamide and dorzolamide when added to the
      combination therapy of latanoprost and a beta-blocker in patients with glaucoma.
AB  - PURPOSE: Brinzolamide and dorzolamide are often used as adjunctive therapy to
      other antiglaucoma agents. The purpose of this study was to compare the efficacy
      and safety of brinzolamide 1% versus dorzolamide 1% when added to the combination
      therapy of latanoprost and a beta-blocker in patients with glaucoma. METHODS: An
      8-week, randomized, open-label comparative study was performed in 52 patients
      with glaucoma. Brinzolamide 1% (twice a day) or dorzolamide 1% (3 times a day)
      was randomly administered to the patients who had been treated with both
      latanoprost and a betablocker. RESULTS: Intraocular pressure (IOP) were both
      decreased significantly (P < 0.0001) from 18.6 +/- 2.3 mmHg to 16.7 +/- 2.3 mmHg
      and from 18.4 +/- 2.6 mmHg to 16.6 +/- 2.5 mmHg, respectively, 8 weeks after the
      addition of brinzolamide or dorzolamide. However, the difference between the
      groups was not significant (P = 0.86). The incidence of ocular irritation was
      significantly higher (P < 0.0001) in the dorzolamide group (74%) than the
      brinzolamide group (16%), but there was no significant difference in blurred
      vision between the groups (dorzolamide 37% versus brinzolamide 52%, P = 0.40).
      CONCLUSIONS: We concluded that the efficacy of brinzolamide 1% was equivalent to
      dorzolamide 1%; however, the safety of brinzolamide 1% was superior to
      dorzolamide 1% as adjunctive therapy to the combination with latanoprost and a
      beta-blocker.

PMID- 15857285
TI  - ErbB family of receptors include 4 different receptors, each of which, with the
      exception of ErbB 2, has a number of ligands.

PMID- 15857286
TI  - The ErbB receptors and their ligands in cancer: an overview.
AB  - This review article provides an overview on the most recent advances on the role
      of ErbB receptors and growth factors of the epidermal growth factor (EGF)-family
      of peptides in cancer pathogenesis and progression. The ErbB tyrosine kinases and
      the EGF-like peptides form a complex system. In fact, the interactions occurring
      between receptors and ligands of these families affect the type and the duration
      of the intracellular signals that derive from receptor activation. Interestingly,
      activation of ErbB receptors is also driven by different classes of membrane
      receptor, suggesting that ErbB kinases can amplify growth promoting signals
      carried by different pathways. The importance of ErbB receptors and EGF-like
      peptides in development of organs and tissues has been demonstrated by using
      different mouse models. In vitro and in vivo studies have also shown that ErbB
      receptors and their ligands can act as transforming genes. However, evidence
      suggests that cooperation of different receptors and ligands is necessary to
      induce a fully transformed phenotype. Indeed, co-expression of different ErbB
      receptors and EGF-like growth factors is a common phenomenon in human primary
      carcinomas. This observation suggests that the growth and the survival of
      carcinoma cells is sustained by a network of receptors/ligands of the ErbB
      family. In this respect, the contemporary expression of different ErbB tyrosine
      kinases and/or EGF-like growth factors in human carcinomas might also affect
      tumor response to target based agents directed against the ErbB receptor/ligand
      system.

PMID- 15857287
TI  - Small molecules with EGFR-TK inhibitor activity.
AB  - Specific and reversible EGFR tyrosine kinase inhibitors (TKI) such as gefitinib
      and erlotinib are clinically active in advanced or metastatic NSCLC and both are
      approved in various countries for the treatment of patients that failed prior
      chemotherapy. Erlotinib has also prolonged survival in pancreatic cancer patients
      when added to gemcitabine and regulatory approval in this disease is being
      sought. Additional promising activity has been seen in other tumor types, such as
      ovarian cancer or head and neck malignancies, and phase III trials in these
      malignancies are ongoing or planned. Despite these successes, these agents have
      exhibited anecdotal or modest activity when used as single agents in unselected
      patients with various other tumor types. We have learned that the clinical
      development of these agents is far from simple and we need to better understand
      biological and clinical criteria for patient selection and how to best use the
      different available agents. The recent discovery of EGFR mutations and the
      potential identification of other markers that might predict patient response
      could help to optimize the use of these agents in the future. Irreversible EGFR
      inhibitors, dual EGF/HER2 and pan-ErbB receptor inhibitors may have greater
      antitumor activity although the tolerance of these compounds compared to specific
      EGFR TKIs needs further characterization. HER2 specific TKIs are also in
      development. Lapatinib, a dual EGFR/HER2 TK inhibitors, is particularly promising
      in breast cancer. Newer agents, such as BMS-599626, have recently entered into
      the clinic. In addition to the use of these agents as single agents, many
      clinical studies are addressing the role of combining them with hormonal agents,
      biological agents or chemotherapy.

PMID- 15857288
TI  - Monoclonal antibodies targeting the epidermal growth factor receptor.
AB  - The epidermal growth factor receptor (EGFR, HER1) autocrine pathway contributes
      to a number of highly relevant processes in cancer development and progression,
      including cell proliferation, regulation of apoptotic cell death, angiogenesis
      and metastatic spread. The crucial role that EGFR plays in human cancers has led
      to an extensive search for selective inhibitors of its signaling pathway. The
      results of a large body of preclinical studies and clinical trials thus far
      conducted suggest that targeting the EGFR could bring a significant contribution
      to cancer therapy. A variety of different approaches are currently being used to
      target the EGFR. The most promising strategies in clinical development include
      monoclonal antibodies, to prevent ligand binding, and small molecules inhibitors
      of the tyrosine kinase enzymatic activity, that inhibit autophosphorylation and
      downstream intracellular signaling. Several blocking monoclonal antibodies
      against the EGFR have been developed. Among these, IMC-225 is a chimeric human
      mouse monoclonal IgG1 antibody that has been the first anti-EGFR targeted therapy
      to enter clinical evaluation in cancer patients in Phase II and III studies,
      alone or in combination with conventional radiotherapy and chemotherapy. However,
      other antibodies against EGFR have demonstrated antitumor activity in several
      preclinical models of human cancer and are currently under investigation in the
      clinical setting, such as ICR62, ABX-EGF and EMD72000. This review will focus on
      all the preclinical data available on monoclonal antibodies engineered against
      the EGF receptor.

PMID- 15857289
TI  - Antitumor therapeutic strategies based on the targeting of epidermal growth
      factor-induced survival pathways.
AB  - Cellular receptors for the Epidermal Growth Factor are considered important
      targets for the experimental treatment of human cancer. Monoclonal antibodies as
      well as small tyrosine kinase inhibitors have been developed and have undergone
      extensive evaluation in preclinical and clinical studies. Most of these studies
      have been conceived on the general idea that epidermal growth factor receptor
      (EGFR) plays a critical role on the growth and survival of human tumors. This
      assumption has been derived by the successful development of BCR/ABL tyrosine
      kinase inhibitors in human chronic myeloid leukemia as well as on the activity of
      antiCD20 monoclonal antibodies in lymphoproliferative disease and of anti HER2
      agents in breast tumors overexpressing the targeted antigens. It is now becoming
      clear that factors regulating sensitivity to kinase inhibitors may differ from
      monoclonal antibodies and that the molecules targeted by interferring drugs must
      be prioritaire for growth and survival of those specific tumors in order to
      achieve valuable results. Recent evidence of major responses to the EGFR
      inhibitor Gefitinib in tumors harboring activating mutations in the EGFR appears
      on line with this concept. In this article we will discuss the significance of
      targeting the EGFR driven survival pathways. Specifically, we will afford the
      point of EGFR survival signalling prioritization by means of pharmacological
      treatment. Finally, we will address the role of profiling technologies and of
      novel computational system biology-based approaches for identification of
      innovative strategies for effective targeting of EGFR driven survival pathways.

PMID- 15857290
TI  - Isoprenylation of intracellular proteins as a new target for the therapy of human
      neoplasms: preclinical and clinical implications.
AB  - Cell proliferation, differentiation, and survival are regulated by a number of
      extracellular hormones, growth factors, and cytokines in complex organisms. The
      transduction of the signals by these factors from the outside to the nucleus
      often requires the presence of small intracellular proteins (i.e. ras and other
      small G proteins) that are linked to the plasma membrane through a isoprenyl
      residue that functions as hydrophobic anchor. Isoprenylation is a complex process
      regulated by different enzymatic steps that could represent potential molecular
      targets for anti-cancer strategies. In the present paper the different
      transduction pathways regulated by some isoprenylated proteins such as ras and
      other small G proteins are described. Moreover, the molecular mechanisms of the
      isoprenylation process and the mode of action of the different isoprenylation
      inhibitors are discussed with attention to statins, farnesyltransferase
      inhibitors (FTI) and aminobisphosphonates. The role of different candidate
      targets in the determination of anti-tumour effects by FTIs is also described in
      order to define potential molecular markers predictor of clinical response. On
      the basis of several preclinical data, new strategies based on multi-step enzyme
      inhibition or on target prioritization are proposed in order to enhance the anti
      tumour activity of agents inhibiting isoprenylation. Finally, a summary of the
      principal data on clinical trials based on the use of FTIs and statins is given.
      In conclusion, the inhibition of isoprenylation is an attractive, but still not
      completely investigated therapeutic alternative that requires optimization for
      the translation in the current treatment of neoplasms.

PMID- 15857291
TI  - Drugging cell cycle kinases in cancer therapy.
AB  - Cell cycle kinases are comprised of cyclin-dependent kinases (Cdks), non-Cdk
      kinases such as Plk-1 and Aurora and checkpoint proteins such as Chk1 and Chk2.
      Though ubiquitous to dividing cells, many cell cycle kinases are amplified or
      over-expressed in malignancy and are potential targets for anti-cancer therapies.
      Cdk inhibiting drugs (such as flavopiridol, UCN-01, E7070, R-Roscovitine and BMS
      387032) have shown preclinical and clinical anticancer activity. However, many of
      these agents are promiscuous and undiscerning, targeting other non-cell cycle
      kinases and affecting normal cells, thereby causing significant toxicity. To
      overcome this, a new generation of Cdk inhibitors are in development with greater
      target specificity, as well as others that inhibit non-Cdk cell cycle kinases,
      both directly and indirectly. The outcome of early clinical trials involving
      these agents is awaited, but these certainly represent a promising new area of
      anticancer drug development.

PMID- 15857292
TI  - Multiple-target drugs: inhibitors of heat shock protein 90 and of histone
      deacetylase.
AB  - In spite of the improvement of conventional medical therapy for cancer treatment,
      the impact on cancer related mortality in the last ten years has been modest
      especially for advanced disease in adults. On the other hand, understanding of
      molecular events underlining tumor development lead to the definition of new
      molecular targets for novel anti-tumor therapeutical approaches. On this regard,
      several biotechnology products selected by academic as well as industrial
      research are currently in clinical trials. Epigenetics as well as post
      translational modifications of proteins are emerging as novel attractive targets
      for anticancer therapy. In addition, the heterogeneity of tumor cells within a
      selected neoplastic lesions as well as the redundancy of proliferative and
      survival pathways present in cancer cells favor the development of single drugs
      that are able to affect multiple pathways. Inhibitors of heat shock protein 90
      and of histone deacetylase are two novel classes of multi-target agents that
      entered recently in clinical studies. This review will focus on the most
      important issues in the development of both these classes of agents.

PMID- 15857293
TI  - Molecular targets for design of novel inhibitors to circumvent aminoglycoside
      resistance.
AB  - Aminoglycosides are a class of clinically important antibiotics used in the
      treatment of infections caused by Gram-positive and Gram-negative organisms. They
      are bactericidal, targeting the bacterial ribosome, where they bind to the A-site
      and disrupt protein synthesis. Antibiotic resistance is a growing problem for all
      classes of anti-infective agents. One of the first groups of antibiotics to
      encounter the challenge of resistance was the aminoglycoside -aminocyclitol
      family. Initially, the resistance that emerged in organisms such as Mycobacterium
      tuberculosis was restricted to modification of the antibiotic targets, which we
      now know to be the bacterial ribosomal rRNA and proteins. As new aminoglycosides
      came to the clinic, however, the prevalence of chemical modification mechanisms
      of resistance became dominant. Enzymatic modification of aminoglycosides through
      kinases (O-phosphotransferases, APHs), O-adenyltransferases (ANTs) and N
      acetyltransferases (AACs) has emerged in virtually all clinically relevant
      bacteria of both Gram-positive and Gram-negative origin. Although their clinical
      use has been extensive, their toxicity and the prevalence of resistance in
      clinical strains have prompted the pharmaceutical industry to look for
      alternatives. Whereas the search for novel targets for antibiotics from the
      genomic information is ongoing, no antibacterial agent based on these efforts has
      so far entered clinical trials. Meanwhile, structural knowledge of the ribosome,
      the target for aminoglycosides, has invigorated the field of antibiotic
      development. It is expected that knowledge of the binding interactions of
      aminoglycosides and the ribosome would lead to concepts in drug design that would
      take us away from the parental structures of aminoglycosides in the direction of
      different structural classes that bind to the same ribosomal target sites as
      aminoglycosides. The challenge to ensure the continued use of these highly potent
      antibacterial agents will require the effective management of resistance at
      several levels. One potential mechanism of circumventing resistance is the
      development of inhibitors of modification enzymes, a methodology that is now well
      established in the beta-lactam field. This approach requires knowledge of
      resistance at the molecular and atomic levels for the rational design of
      inhibitory molecules. The understanding of the molecular basis for aminoglycoside
      resistance modification has been greatly enhanced by the recent availability of
      representative 3D-structures from the three classes of modifying enzymes:
      kinases, acetyltransferases and adenyltransferases. The challenge is now to
      firmly establish the mechanisms of enzyme action and to use this information to
      prepare effective and potent inhibitors that will reverse antibiotic resistance.
      In this review, we discuss the molecular mechanisms of resistance of
      aminoglycosides specifically on aminoglycoside-modifying enzymes and newly
      developed strategies to circumvent resistance including antisense technology,
      which is an example of new strategy to deal with antibiotic resistance.

PMID- 15857294
TI  - Colloidal carriers for ophthalmic drug delivery.
AB  - To achieve effective drug concentration at the intended site for a sufficient
      period of time is a requisite desired for many drug formulations. For drugs
      intended to ocular delivery, its poor bioavailability is due to pre-corneal
      factors. Most ocular diseases are treated by topical drug application in the form
      of solution, suspension and ointment. However, such dosage forms are no longer
      sufficient to combat some ocular diseases. Intravitreal drug injection is the
      current therapy for disorders in posterior segment. The procedure is associated
      with a high risk of complications, particularly when frequent, repeated
      injections are required. Thus, sustained-release technologies are being proposed,
      and the benefits of using colloidal carriers in intravitreal injections are
      currently under investigation for posterior drug delivery. This review will
      discuss recent progress and specific development issues relating to colloidal
      drug delivery systems, such as liposomes, niosomes, nanoparticles, and
      microemulsions in ocular drug delivery.

PMID- 15857295
TI  - Free radical trapping as a therapeutic approach to neuroprotection in stroke:
      experimental and clinical studies with NXY-059 and free radical scavengers.
AB  - There is substantial experimental evidence that free radicals are produced in the
      brain during ischemia, during reperfusion and during intracranial hemorrhage.
      Removal of pathologically produced free radicals is therefore a viable approach
      to neuroprotection. Four compounds with free radical scavenging activity
      (tirilazad, ebselen, edaravone) or free radical trapping properties (NXY-059)
      have been examined in experimental models of stroke and evaluated clinically as
      neuroprotective agents. Both experimental and clinical results are reviewed in
      this article. Ebselen was a modestly effective neuroprotectant in a rat transient
      middle cerebral artery occlusion (MCAO) model when given before the start of
      ischemia, but not when the insult was severe. Data from the permanent MCAO model
      and an embolic stroke model suggested a bell shaped dose-response curve. The weak
      preclinical profile may explain the lack of success in clinical trials.
      Preclinical data on tirilazad in animal models of acute ischemic stroke are
      neither comprehensive nor consistent. There was little evidence of efficacy in
      permanent MCAO or when the drug was given several hours post-occlusion. This may
      explain the negative clinical trials as these did not target patients likely to
      reperfuse and treatment started several hours after stroke onset. While
      preclinical data on subarachnoid hemorrhage demonstrated an attenuation of
      vasospasm the clinical data were inconsistent. There is very limited published
      preclinical data on edaravone but it has been approved in Japan as a
      neuroprotectant for the treatment of stroke. Evidence is based on a single
      placebo controlled trial in a relatively small number of patients. The status of
      possible development of edaravone outside of Japan is not known. NXY-059 has been
      found to be a very effective agent in transient and permanent MCAO and
      thromboembolic models of acute ischemic stroke. Its preclinical development has
      been governed by adherence with the recommendations of the Stroke Therapy
      Academic Industry Roundtable (STAIR) group and is now being investigated in Phase
      III clinical trials using a therapeutic time window and plasma concentrations
      that are effective in rat and primate models of stroke.

PMID- 15857296
TI  - Repinotan, A 5-HT1A agonist, in the treatment of acute ischemic stroke.
AB  - Serotonin agonists can reduce glutamate-induced excitotoxicity in cerebral
      ischemia. The potent 5-HT1A agonist BAY x 3702, or repinotan, has reduced
      cortical infarct volume in pre-clinical models even when given 5 hours after
      injury. Early clinical trials showed that the drug was safe, and displayed
      primarily serotonergic side effects such as nausea and vomiting. A phase IIb
      trial in moderate to moderately severe strokes completed enrollment in June 2004.

PMID- 15857297
TI  - Growth factor treatment of stroke.
AB  - This review discusses the potential usefulness of several selected polypeptide
      growth factors as treatments for stroke. Distinctions between global vs. focal
      cerebral ischemia, permanent vs. temporary focal ischemia, and acute stroke vs.
      stroke recovery are first discussed. Potential routes of administration of growth
      factors are also considered. The growth factors basic fibroblast growth factor
      (bFGF), osteogenic protein-1 (OP-1), vascular endothelial growth factor (Veg-f),
      erythropoietin (EPO), and granulocyte colony stimulating factor (G-CSF) all show
      potential usefulness in animal models of acute stroke and stroke recovery. Two of
      these factors, bFGF and EPO, have reached human clinical trials for acute stroke,
      and the data are discussed. Future directions in this field are also discussed.

PMID- 15857298
TI  - Arundic acid (ONO-2506) ameliorates delayed ischemic brain damage by preventing
      astrocytic overproduction of S100B.
AB  - After focal cerebral ischemia, the infarct volume increases rapidly within acute
      infarct expansion (initial 12 to 24 h) and continues slowly during delayed
      infarct expansion (25 to 168 h). While acute infarct expansion represents
      progressive necrosis within the ischemic core, delayed infarct expansion starts
      as disseminated apoptotic cell death in a narrow rim surrounding the infarct
      border, which gradually coalesces to form a larger infarct. Discovery of a
      distinct correlation between reactive astrogliosis along the infarct border and
      delayed infarct expansion in the rodent ischemia model led us to investigate the
      possible causal relationship between the two events. Specifically, the calcium
      binding protein S100B exerts detrimental effects on cell survival through
      activation of various intracellular signaling pathways, resulting in altered
      protein expression. Arundic acid [(R)-(-)-2-propyloctanoic acid, ONO-2506] is a
      novel agent that inhibits S100B synthesis in cultured astrocytes. In the rodent
      ischemia model, this agent was shown to inhibit both the astrocytic
      overexpression of S100B and the subsequent activation of signaling pathways in
      the peri-infarct area. Concurrently, delayed infarct expansion was prevented, and
      neurologic deficits were promptly ameliorated. The results of subsequent studies
      suggest that the efficacy of arundic acid is mediated by restoring the activity
      of astroglial glutamate transporters via enhanced genetic expression.

PMID- 15857299
TI  - NMDA/NR2B selective antagonists in the treatment of ischemic brain injury.
AB  - Glutamate is the main excitatory neurotransmitter in the central nervous system
      and it plays a significant role not only in synaptic transmission but also in
      acute and chronic neuropathologies including stroke. Presently, four receptors
      for glutamate have been identified and the NMDA receptor family is the most
      intensively studied. A number of NMDA receptor antagonists have been developed
      and used for treatment of neurological diseases in patients. However, all of
      these drugs have been failed in clinical trials either because of intolerable
      side effects or lack of medical efficacy. Recently, the understanding of
      molecular structure of NMDA receptors has been advanced and this finding thus
      provides information for designing subtype-selective antagonists. Using NR2B
      subunit selective antagonists, ifenprodil and eliprodil, as basic structure
      models, second and third generation congeners have been developed. Several NR2B
      selective compounds showed neuroprotective actions at doses that did not produce
      measurable side effects in preclinical studies. Some of NR2B subunit selective
      antagonists have also been tested for the treatment of ischemic brain injury. The
      present review describes the role of glutamate in ischemic brain injury with an
      emphasis on the NR2B containing NMDA receptors.

PMID- 15857300
TI  - AMPA receptor antagonists for the treatment of stroke.
AB  - Signal transduction via ionotropic glutamate receptors is found in many life
      forms, from protozoa to mammals. Glutamate is the main excitatory
      neurotransmitter in the mammalian CNS, were fast postsynaptic depolarisation is
      induced by the activation of AMPA (alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid) receptors. In addition to their important physiological
      role, excessive AMPA receptor stimulation is also a hallmark of excitotoxicity
      related diseases, like ischaemic stroke. Conversely, AMPA receptor inhibitors
      were proposed to be useful neuroprotective drugs. First generation AMPA receptor
      blockers were competitive antagonists, like NBQX, which showed robust
      neuroprotection in a variety of disease-related animal models. Its clinical use,
      however, was restricted by the very low solubility, inducing kidney precipitaton
      in vivo. Second generation competitive antagonists are available, which do not
      possess this property. None of those, however, up to now is in clinical use.
      Competitive AMPA receptor antagonists are not the first choice for
      neuroprotective drugs, since due to receptor kinetics they preferently suppress
      the physiological relevant component of the postsynaptic glutamate response. Non
      competitive blockers, like 2,3-benzodiazepines or the novel neuroprotectant BIIR
      561 should be suited better for the treatment of stroke. The latter compound is
      also described as blocker of voltage-gated sodium channels. Targetting more than
      one mechanism in the excitotoxicity cascade might be a fruitful approach for the
      development of neuroprotective drugs.

PMID- 15857301
TI  - Therapeutic potential of TACE inhibitors in stroke.
AB  - Stroke is the third leading cause of death and the leading cause of permanent
      disability in western countries and the incidence of stroke is expected to
      increase in the foreseeable future due to the ageing population. The effective
      treatment of stroke remains challenging due to the complexity and heterogenicity
      of the disease. Recombinant tissue plasminogen activator (rt-PA) is the only FDA
      approved therapy for stroke during the first 3 hr after the disease onset.
      However the risk of hemorrhage and its narrow therapeutic window has limited its
      use in clinic. Inflammation has been known to play a crucial role in the
      induction and development of stroke and tumor necrosis factor-alpha (TNF-alpha)
      is a central player in the initiation of multiple inflammatory cascades. The
      recent success of three anti-TNF biologics in the clinic for the treatment of
      rheumatoid arthritis as well as other inflammatory diseases has further validated
      TNF159nflammation. TNF-alpha has also been shown to be associated with ischemic
      stroke. Anti-TNF biologics have been shown to be effective in reducing the
      disease symptoms in various pre-clinical stroke models. Small molecule TNF
      inhibitors are highly desirable due to the limitations of protein therapeutics.
      Tumor necrosis factor-alpha-converting enzyme (TACE) is the major sheddase of TNF
      alpha and is essential for the generation of soluble, mature TNF-alpha. Thus TACE
      appears to be an attractive target for development of oral small molecule TNF
      alpha inhibitors. This review summarizes the role of TNF-alpha in stroke and the
      effect of several TACE/MMP inhibitors in pre-clinical stroke models. The data
      strongly suggest that TACE/MMP inhibitors have great therapeutic potential and
      may be valuable alternatives in treating stroke in the clinic.

PMID- 15857302
TI  - Estrogens as protectants of the neurovascular unit against ischemic stroke.
AB  - Estrogens are now recognized as potent neuroprotectants in a variety of in vitro
      and in vivo model for cerebral ischemia. These protective effects of estrogens
      are seen in neurons, astrocytes, microglia and vascular endothelial cells and
      result in a profound protection of the brain during stroke. Herein, we provide a
      thesis that indicates that the protective effects of estrogens during stroke may
      be a combined effect on multiple targets of the neurovascular unit (NVU) through
      a fundamental protective effect of estrogens on the subcellular organelle that
      defines the fate of cells during insults, the mitochondria. By protecting
      mitochondria during insult, estrogens are able to reduce or eliminate the signal
      for cellular necrosis or apoptosis and thereby protect the NVU from
      ischemia/reperfusion. In this context, estrogens may be unique in their ability
      to target the cellular site of initiation of damage during stroke and could be a
      central compound in a multi-drug approach to the prevention and treatment of
      brain damage from stroke.

PMID- 15857303
TI  - Poly (adp-ribose) polymerase inhibitors as potential therapeutic agents in stroke
      and neurotrauma.
AB  - Poly (ADP-ribose) polymerase-1 (PARP-1) is a DNA-binding protein that is
      primarily activated by nicks in the DNA molecule. It regulates the activity of
      various enzymes - including itself- that are involved in the control of DNA
      metabolism. Upon binding to DNA breaks, activated PARP cleaves NAD+ into
      nicotinamide and ADP-ribose and polymerizes the latter on nuclear acceptor
      proteins including histones, transcription factors and PARP itself. Poly(ADP
      ribosylation) contributes to DNA repair and to the maintenance of genomic
      stability. Evidence obtained with pharmacological PARP inhibitors of various
      structural classes, as well as animals lacking the PARP-1 enzyme indicate that
      PARP plays an important role in cerebral ischemia/reperfusion, stroke and
      neurotrauma. Overactivation of PARP consumes NAD+ and ATP culminating in cell
      dysfunction and necrosis. PARP activation can also act as a signal that initiates
      cell death programs, for instance through AIF (apoptosis inducing factor)
      translocation. PARP has also been shown to associate with and regulate the
      function of several transcription factors. Of special interest is the enhancement
      by PARP of NF-kappaB-mediated transcription, which plays a central role in the
      expression of inflammatory cytokines, chemokines, adhesion molecules and
      inflammatory mediators. Via this mechanism, PARP is involved in the up-regulation
      of numerous pro-inflammatory genes that play a pathogenetic role in the later
      stage of stroke and neurotrauma. Here we review the roles of PARP in DNA damage
      signaling and cell death, and summarize the pathogenetic role of PARP in stroke
      and neurotrauma.

PMID- 15857304
TI  - Pharmacological approaches to functional recovery after spinal injury.
AB  - Locomotion results from the activity in neural networks in the spinal cord that
      together with sensory and descending inputs generate coordinated motor outputs.
      Descending inputs include glutamatergic, monoaminergic, and peptidergic pathways.
      Spinal injuries interrupt these descending pathways, resulting in the disruption
      or loss of function. Drugs that target these endogenous transmitter systems have
      been used to improve function after spinal injury. However, individual drugs can
      have beneficial or deleterious effects in different studies and thus there is
      little consensus on optimal pharmacological strategies. The variability may be
      influenced by changes introduced by the type of lesion (complete or partial),
      time after injury, or the lack of specific ligands that target specific
      transmitter systems. It is now recognised that these transmitter systems do not
      necessarily act in isolation, but can interact to evoke additive, inhibitory, or
      novel metamodulatory effects. Meta interactions mean that differing chemical
      environments in lesioned spinal cords could influence drug effects. The spinal
      cord also exhibits injury-induced changes, which could alter the chemical
      environment and functional properties over time. While they have not been
      considered in pharmacological approaches to spinal injury, interactive and
      adaptive changes could influence the effects of spinal lesions and therapeutic
      interventions. The properties of endogenous transmitter systems in spinal
      locomotor networks before and after spinal lesions need to be understood, and
      pharmacological tools that target specific functional aspects need to be
      developed.

PMID- 15857305
TI  - Glutamate transporters as drug targets.
AB  - The L-glutamate (Glu) has been hypothesized as an excitatory amino acid
      neurotransmitter in the mammalian central nervous system after successful cloning
      and identification of a number of genes encoding signaling machineries required
      for the neurocrine at synapses in the brain. These include excitatory amino acid
      transporters (EAATs) for signal termination and vesicular Glu transporters
      (VGLUTs) for signal output through exocytotic release, in addition to Glu
      receptors (GluRs) for signal input. These Glu signaling molecules not only play
      key roles in mechanisms associated with synaptic plasticity such as learning and
      memory, but also participate in the etiology and pathology of different
      neuropsychiatric disorders and neuronal cell death seen in various
      neurodegenerative diseases. Of the aforementioned Glu signaling molecules, EAATs
      are essential for the termination of signal transmission mediated by Glu as well
      as for the prevention of neurotoxicity mediated by this endogenous excitotoxin,
      while VGLUTs are crucial for the storage of Glu in synaptic vesicles to suffice
      for the definition of a glutamatergic phenotype. Many early desperate efforts
      were devoted to the search and development of novel compounds with a therapeutic
      window toward GluRs, while relatively little attention was paid to either EAATs
      or VGLUTs in this aspect. In this review, therefore, we will summarize the
      classification and functionality of EAATs and VGLUTs with a focus on their
      possibilities as potential therapeutic targets for different neurodegenerative
      and neuropsychiatric disorders related to malfunction of Glu signaling in human
      beings.

PMID- 15857307
TI  - New lipid-lowering agents acting on LDL receptors.
AB  - The treatment of dyslipoproteinemia has proven a successful strategy in the
      prevention of cardiovascular diseases. The major target of hypolipidemic drugs is
      the reduction of low density lipoprotein cholesterol (LDL-C). HMG-CoA reductase
      inhibitors (HMGRI) effectively lower LDL-C by inhibiting the mevalonate pathway
      and enhancing the activity of the LDL receptor (LDL-R). Numerous clinical studies
      demonstrated convincingly, that the reduction of LDL-C lowers the incidence of
      cardiovascular events in primary and secondary prevention. Two new HMGRI,
      rosuvastatin and pitavastatin, have been evaluated in clinical trials. Both drugs
      demonstrated efficacy in lowering atherogenic lipoproteins. In addition to the
      reduction of LDL-C, they may have a higher potency to lower triacylglycerides
      (TG) and to increase HDL cholesterol (HDL-C) compared to currently available
      HMGRI. Other therapeutic strategies examined in experimental animals are the
      inhibition of squalene synthase, the first enzyme of the mevalonate pathway,
      which is specifically committed to cholesterol biosynthesis, and the direct up
      regulation of LDL receptor activity. The latter compounds, the SCAP ligands, are
      the first members of a new class of hypolipidemic agents affecting the
      transcriptional regulation of genes involved in lipid metabolism. Recent
      treatment guidelines emphasise the importance of modifying lipid metabolism
      beyond lowering LDL-C, mainly by lowering TG and raising HDL-C. Although these
      actions are not primary targets of the compounds discussed here, it is
      interesting that drugs inducing the LDL-R usually also lower TG and, in the case
      of HMGRI, increase HDL-C.

PMID- 15857308
TI  - Ezetimibe and other azetidinone cholesterol absorption inhibitors.
AB  - Atherosclerotic coronary artery disease remains a major healthcare concern
      especially in developed countries. While lowering plasma cholesterol levels via
      diet, exercise, and pharmacotherapy can reduce this risk of developing coronary
      artery disease, there remains a need for more effective drug therapies. The
      azetidinone cholesterol absorption inhibitors typified by ezetimibe represent the
      first new approach to lipid lowering therapy in more than a decade. This review
      summarizes the medicinal chemistry of the azetidinone cholesterol absorption
      inhibitors as a class, with emphasis on factors that contributed both to the
      discovery of ezetimibe as well as to our overall understanding of S.A.R. trends
      in this area.

PMID- 15857309
TI  - Cholesteryl ester transfer protein: pharmacological inhibition for the modulation
      of plasma cholesterol levels and promising target for the prevention of
      atherosclerosis.
AB  - Cholesteryl ester transfer protein (CETP) facilitates the exchange of neutral
      lipids (such as cholesteryl esters and triglycerides) between anti-atherogenic
      HDL particles and pro-atherogenic VLDL and LDL particles in human plasma.
      Individuals possessing a genetic deficiency for CETP have higher HDL cholesterol
      and lower LDL cholesterol and may have a reduced risk for developing
      cardiovascular disease. Small molecule inhibitors of CETP are being developed
      that would appear to provide a beneficial change in lipoprotein profile. However,
      randomized clinical trials are ultimately required to determine whether CETP
      inhibition will afford a reduction in cardiovascular events.

PMID- 15857310
TI  - Nuclear receptors as potential targets for modulating reverse cholesterol
      transport.
AB  - This review describes the role of nuclear receptors in the regulation of genes
      involved in cholesterol transport and synthetic modulators of these receptors.
      Increasing the efflux of cholesterol from peripheral cells, such as lipid-laden
      macrophages, through a process called reverse cholesterol transport (RCT)
      requires HDL. Increasing the circulating levels of HDL, as well as the efficiency
      of the RCT process, could result in a reduction in the development of coronary
      artery disease and atherosclerosis. Nuclear receptors of the RXR heterodimer
      family have recently been shown to regulate key genes involved in HDL metabolism
      and reverse cholesterol transport. These include the PPARs (peroxisome
      proliferator activated receptors), the LXR (liver X receptor) and the farnesoid X
      receptor (FXR). The synthesis of specific and potent ligands for these receptors
      has aided in ascertaining the physiological role of these receptors as lipid
      sensors and the potential therapeutic utility of modulators of these receptors in
      dyslipidemias and cardiovascular disease.

PMID- 15857311
TI  - Current biology of MTP: implications for selective inhibition.
AB  - The microsomal triglyceride transfer protein (MTP), along with its partner,
      protein disulphide isomerase, performs a wide range of lipid transport functions
      necessary for maintenance of whole-body lipid homeostasis. In this review, we
      summarize the recent deluge of comparative and functional genomic data that have
      forced a radical re-appraisal of the evolutionary processes that established the
      major lipid transport pathway in man, and the different structural and lipid
      transfer roles MTP plays within it. This is followed by an overview of MTP
      structure-function relationships, highlighting two newly identified functional
      roles: first, the production of small, apolipoprotein (apo)B-containing
      lipoprotein particles in cardiac myocytes and, second, the lipidation of a major
      histocompatibility complex class-I related molecule (CD1d) that presents
      glycolipid antigens to distinct subsets of natural killer T cells. We also
      discuss the interactions of MTP with proteins such as apoB and CD1d, and the
      complex mechanisms regulating MTP transcription in different cell types and
      nutritional states. The past five years has witnessed remarkable progress in
      teasing out the different functionalities of MTP, and the properties of the
      different molecules that inhibit MTP activity, data that are likely to underpin
      the design of the next generation of MTP/apoB inhibitors for preventing
      cardiovascular disease attributable to the increased production of atherogenic
      lipoproteins.

PMID- 15857313
TI  - Pharmacological characterization of human kappa/mu opioid receptor chimeras that
      retain high affinity for dynorphin A.
AB  - Arylacetamide analgesics that stimulate kappa opioid receptors in the central
      nervous system mediate dysphoria and psychosis as well as analgesia. However, the
      naturally occurring peptide agonist, dynorphin A, is analgesic in the absence of
      dysphoria and psychosis, indicating that the therapeutic effects of kappa opioid
      agonists may be separated from their side effects. As part of our effort to
      discover kappa opioid receptor analgesics lacking side effects, we designed and
      constructed two mu/kappa chimeric receptors, composed primarily of amino acid
      residues derived from the mu opioid receptor, that were expected to bind
      dynorphin A with high affinity. In one, extracellular loop 2 and transmembrane
      domain 4 were derived from the kappa opioid receptor and in the other, only
      extracellular loop 2 was derived from the kappa opioid receptor. Most competitors
      of [(3)H]diprenorphine binding from a variety of structural classes bound to the
      chimeras with affinities similar to those with which they bound to the mu opioid
      receptor. In contrast, dynorphin A analogs bound to the chimeras with affinities
      similar to those with which they bound to the kappa opioid receptor.
      Pharmacological characterization of [(35)S]GTPgammaS binding mediated by the
      chimera with extracellular loop 2 derived from the kappa opioid receptor showed
      that it behaved as if it were mu opioid receptor with high affinity for dynorphin
      A analogs. These chimeras may be useful in identifying novel kappa receptor
      agonists that bind to the second extracellular loop of the receptor and share the
      desirable therapeutic profile of dynorphin A.

PMID- 15857314
TI  - G protein-coupled receptor structural motifs: relevance to the opioid receptors.
AB  - As a whole, the G protein-coupled receptor (GPCR) superfamily displays no overall
      sequence homology. Nevertheless, enough short sequences and even individual amino
      acid residues are shared by these receptors to afford a common three-dimensional
      structure and a similar signal transduction mechanism. Some of these sequence
      commonalities, or structural motifs, are dedicated to preserving receptor
      infrastructure, while others are critical to agonist-mediated signaling. Certain
      structural motifs common to GPCRs and other signal transducing integral membrane
      proteins are present in the conventional opioid receptors, although several of
      the motifs are not well characterized in this receptor family. Here we focus on
      six structural motifs found in the mu, delta and kappa opioid receptors as well
      as the opioid like receptor ORL-1. The motifs are discussed in terms of their
      dynamic roles in the signaling mechanism documented for several Class A GPCRs
      including the opioid receptors. Clarification of the roles of GPCR structural
      motifs provides a blueprint for structure-function studies on newly discovered or
      recently cloned receptors in the superfamily. Characterization of these motifs in
      the opioid receptors should enhance understanding of what makes an opioid ligand
      a full, partial or inverse agonist or antagonist at a given receptor, possibly
      leading to rational design of therapeutics useful for combating opiate dependence
      or for pain management.

PMID- 15857315
TI  - Opioid receptor-like 1 (ORL1) molecular "road map" to understanding ligand
      interaction and selectivity.
AB  - The opioid receptor-like 1 (ORL1) system has attracted a lot of attention owing
      to its diverse physiological role and by its close structural proximity toward
      the classical opioid receptors. Even though they share a close sequence
      similarity, the ligand recognition pattern for the ORL1 receptor and the
      classical opioid receptors remains highly distinct. In addition, functional
      diversification observed between the ORL1 receptor system and classical opioid
      receptors clearly indicates that subtle changes in the structural makeup of a
      receptor are enough to delineate them. A clear understanding of the structural
      requirements for ligand selectivity by classical opioid receptors and
      identification of a common "opioid binding pocket" has not been achieved yet. At
      this juncture, the ORL1 receptor system presents itself as a potential tool in
      the quest for elucidating critical elements directing ligand selectivity. The
      current paper is a compilation of several site-directed mutagenesis studies
      conducted on the ORL1 receptor system. The mutagenesis studies concentrated on
      the transmembrane domain residues are reported with the changes observed in terms
      of both binding and functional activation of the receptor. Given the critical
      role played by this G-protein coupled receptor, molecular level understanding of
      this ORL1 receptor system would aid in rational design and development of
      agonists and antagonists with multiple therapeutic applications.

PMID- 15857316
TI  - Opioid-modulating peptides: mechanisms of action.
AB  - Opioids are involved in the physiological control of numerous functions of the
      central nervous system, particularly nociception. It appears that some endogenous
      neuropeptides, called anti-opioids, participate in an homeostatic system tending
      to reduce the effects of opioids. Neuropeptide FF (NPFF) and cholecystokinin
      (CCK) possess these properties and, paradoxically, the opioid peptides nociceptin
      and dynorphin display some anti-opioid activity. All these peptides exhibit
      complex properties as they are able to both counteract and potentiate opioid
      activity, acting rather as modulators of opioid functions. The purpose of this
      review is to highlight that two different mechanisms are clearly involved in the
      control of opioid functions by opioid-modulating peptides: a circuitry-induced
      mechanism for nociceptin and dynorphin, and a cellular anti-opioid mechanism for
      NPFF and CCK. The knowledge of these mechanisms has potential therapeutic
      interest in the control of opioid functions, notably for alleviating pain and/or
      for the treatment of opioid abuse.

PMID- 15857317
TI  - The function of the extracellular regions in opioid receptor binding: insights
      from computational biology.
AB  - Pain management using opioid analgesics strives to achieve three goals: maximum
      efficacy, minimal risk of tolerance and physical dependence, and negligible side
      effects. Following the cloning of opioid and nociceptin receptors, novel ligands
      can be designed to target specific residues of these membrane proteins with the
      goal of improving efficacy and reducing side effects through selectivity. For the
      most part, ligand design has focused on binding sites located in the
      transmembrane region of the receptors, and has ignored the extracellular domains.
      In this review, we discuss the evidence for the interaction of the extracellular
      regions with opioids and show how computational biology tools can be used to
      model these domains for use in drug discovery. A computational model of the kappa
      opioid receptor which includes the loop regions is presented. The model combines
      knowledge-based information, bioinformatics and computational tools to identify
      regions of the extracellular loop domains that can be targeted by drug design.

PMID- 15857318
TI  - Diabetes in the new General Medical Services contract: targets and adherence to
      metformin therapy.

PMID- 15857319
TI  - Prevention of disease--education makes a difference in the community.

PMID- 15857320
TI  - Barriers to optimal intervention and care for people with dementia.

PMID- 15857321
TI  - Efficacy of escitalopram in patients with severe depression: a pooled analysis.
AB  - Escitalopram is an effective, well-tolerated treatment for major depressive
      disorder in both primary and specialist settings. This analysis compared the
      efficacy of escitalopram with citalopram in the treatment of patients with severe
      depression [defined as a score of > or =30 Montgomery-Asberg Depression Rating
      Scale (MADRS)]. Data from three clinical trials were used for this pooled
      analysis. A total of 506 severely depressed patients were included (169 received
      escitalopram, 171 citalopram and 166 placebo). Mean change from baseline in MADRS
      total scores (primary efficacy parameter) was significantly higher in the
      escitalopram-treated group compared with the citalopram-treated group (p =
      0.003). There was a significant difference in response between escitalopram and
      citalopram (56 vs. 41%, respectively, p = 0.007). Results from secondary efficacy
      parameters (Hamilton rating for depression and Clinical Global Impression of
      Improvement and Severity scales) were consistent with previous results. The
      benefits in severe depression of escitalopram vs. citalopram were so
      demonstrated.

PMID- 15857322
TI  - Factors affecting pain in intravenous catheter placement: role of depression
      illness.
AB  - The aim of the study was to examine factors affecting pain during intravenous
      (IV) catheter placement in an emergency department. A cross-sectional,
      observational study was conducted at an academic emergency department. Nine
      hundred and twenty-five adult patients who had a 20-gauge IV catheter placed were
      enrolled in the study. Patients were excluded for the following conditions: more
      than one IV attempt, altered mental status, head trauma, lack of contact due to
      visual impairment, hearing or speech disorder, intoxication, distracting injury
      or physical abnormality at the IV site. The magnitude of pain in IV catheter
      placement was not related to age, sex, experience of the individual placing the
      IV catheter, site of IV catheter insertion and use of analgesic or antidepressant
      drugs (p > 0.05). Patients with a history of depression reported significantly
      higher pain than non-depressed patients (p = 0.001). Depressed patients reported
      higher severity of pain during IV catheter placement than non-depressed ones.
      This may influence the decision on whether or not to use local anaesthesia for
      catheter insertion.

PMID- 15857323
TI  - Use of a structured migraine diary improves patient and physician communication
      about migraine disability and treatment outcomes.
AB  - Migraine is frequently undertreated, perhaps because impaired communication
      between patients and physicians underestimate the disability associated with
      migraine attacks. The purpose of this study was to evaluate the benefits of a
      structured migraine diary used during a prospective open-label study of triptan
      naive patients in Spain for recording information on response to therapy for a
      pre-study migraine attack and three consecutive migraine attacks, the first and
      third treated with rizatriptan 10-mg wafer and the second with usual non-triptan
      therapy. Of 97 patients (83% women; mean age, 39 years) who completed the study,
      all reported moderate to severe pain, and two-thirds reported severe to total
      impairment during migraine attacks. At study end, 72% of patients reported that
      the migraine diary helped communication with their doctor about migraine, and 70%
      were more or much more satisfied than before the study with level of overall
      medical care provided by their doctor. Patients who reported the diary to be
      useful also reported higher overall satisfaction with medical care (p < 0.001).
      Most of the 22 physicians (91%) reported that the diary enabled them to better
      communicate with their patients about migraine, and all reported that it enabled
      them to assess differences in pain intensity and disability across patients. We
      conclude that a structured migraine diary can be a valuable aid for improving
      communication between physicians and patients regarding migraine disability and
      treatment outcomes.

PMID- 15857324
TI  - Efficacy of levodopa and carbidopa on visual function in patients with non
      arteritic anterior ischaemic optic neuropathy.
AB  - The benefit of levodopa and carbidopa therapy in improving visual function in
      patients with non-arteritic anterior ischaemic neuropathy (NAION) was evaluated.
      Twenty-four subjects with NAION were randomly selected to receive either levodopa
      carbidopa or a placebo. Visual functions of neither the study nor the placebo
      groups showed improvement. Side effects of levodopa such as dizziness,
      orthostatic hypotension, vomiting and cardiac arrhythmia were seen. Levodopa and
      carbidopa had no therapeutic effect on visual recovery in our patients with
      NAION.

PMID- 15857325
TI  - The medicinal use of cannabis in the UK: results of a nationwide survey.
AB  - The use of cannabis for medical purposes is a controversial but an important
      topic of public and scientific interest. We report on the results of a self
      administered questionnaire study conducted in the United Kingdom between 1998 and
      2002. The questionnaire consisted of 34 items and included demographic data,
      disease and medication use patterns and cannabis use profiles. Subjects were self
      selected; 3663 questionnaires were distributed and 2969 were returned [1805
      (60.9%) women, mean age 52.7 years (SD 12.7)]. Medicinal cannabis use was
      reported by patients with chronic pain (25%), multiple sclerosis and depression
      (22% each), arthritis (21%) and neuropathy (19%). Medicinal cannabis use was
      associated with younger age, male gender and previous recreational use (p <
      0.001). While caution must be exercised in interpreting these data, they point to
      the need for clinical studies of cannabis and cannabinoids with standardised and
      quality-controlled products.

PMID- 15857326
TI  - Telithromycin for the treatment of acute exacerbations of chronic bronchitis.
AB  - Pooled data from three randomized, double-blind, multi- centre studies evaluated
      the efficacy and tolerability of telithromycin 800 mg once daily for 5 days vs.
      standard comparators (10-day amoxicillin-clavulanate 500/125 mg three times
      daily, clarithromycin 500 mg or cefuroxime axetil 500 mg twice daily) in the
      outpatient treatment for acute exacerbations of chronic bronchitis. Per-protocol
      clinical cure rates at post-therapy/test of cure (days 17-24) were 86.0 and 85.8%
      for telithromycin and comparators, respectively, and 79.1 and 78.7%,
      respectively, at late post-therapy (days 31-36). Clinical cure rates were
      comparable for patients at increased risk, including those of > or =65 years and
      those with severe infection or significant airway obstruction (telithromycin, >
      or =77.1%; comparators, > or =75.0%). Telithromycin was well tolerated. Most
      adverse events considered possibly related to study medication were
      gastrointestinal and of mild intensity. In conclusion, 5-day telithromycin
      therapy is as effective and well tolerated as 10-day treatment with standard
      comparators.

PMID- 15857327
TI  - Effects of amlodipine and fosinopril on heart rate variability and left
      ventricular mass in mild-to-moderate essential hypertension.
AB  - The differences between long-acting dihydropyridines and angiotensin-converting
      enzyme inhibitors with regard to their long-term effects on 24-h heart rate
      variability (HRV) and left ventricular (LV) mass are less clear in mild-to
      moderate essential hypertension. We studied the long-term effects of amlodipine
      and fosinopril on 24-h HRV and LV mass in mild-to-moderate essential
      hypertension. In this study, 27 patients with never treated mild-to-moderate
      essential hypertension were randomised to receive either amlodipine or fosinopril
      once daily as monotherapy. At baseline and at the end of the third and sixth
      months, each of the patients underwent 24-h HRV and ambulatory systolic (SBP) and
      diastolic (DBP) blood pressure analysis. LV mass index was calculated from
      echocardiographic examination at baseline and at the end of the sixth month. In
      amlodipine group (n = 14), 24-h SBP/DBP (mmHg) decreased from 144 +/- 8/94 +/- 4
      to 128 +/- 6/83 +/- 3 at the end of the third month and to 125 +/- 5/81 +/- 2 at
      the end of the sixth month (p < 0.0001). In fosinopril group (n = 13), the
      respective changes were 143 +/- 9/97 +/- 7, 132 +/- 6/87 +/- 5 and 127 +/- 6/82
      +/- 3 (p < 0.0001). At the end of the sixth month, LV mass index (g/m(2))
      decreased from 122 +/- 26 to 105 +/- 21 in amlodipine group (p < 0.0001) and from
      118 +/- 23 to 101 +/- 14 in fosinopril group (p < 0.0001). There were no
      significant changes in HRV parameters in both the groups. It was concluded that
      both drugs caused significant decrease in SBP and DBP, and LV mass in patients
      with mild-to-moderate essential hypertension did not have significant long-term
      effects of either amlodipine or fosinopril on 24-h HRV parameters reflecting
      sympathetic or parasympathetic activity in these patients.

PMID- 15857328
TI  - Heterozygote men with familial hypercholesterolaemia may have an abnormal
      triglyceride response post-prandially. Evidence for another predictor of vascular
      risk in familial hypercholesterolaemia.
AB  - Familial hypercholesterolaemia (FH) is associated with premature coronary heart
      disease (CHD). Post-prandial hypertriglyceridaemia has also been associated with
      cardiovascular disease. Thus, an abnormal post-prandial triglyceride (TG)
      clearance may contribute to the heterogeneity in the risk of CHD in heterozygous
      (h) FH. Therefore, we investigated the response of TG levels to a fatty meal in
      men with hFH. We studied 26 Greek men divided into two groups: the hFH group of
      14 men, mean age 39 (SD = 11) years and the control group of 12 healthy men, mean
      age 43 (50:5) years. An increased TG response to the fatty meal was defined as a
      post-prandial TG concentration (at 4, 6 or 8 h) greater than the highest TG
      concentration in any hour in any control individual. All hFH patients had normal
      baseline fasting TG levels. However, seven hFH men showed an abnormal TG response
      after the fatty meal; these patients had higher baseline fasting TG levels than
      others [1.5 (0.2) vs. 1.0 (0.4) mmol/l, p = 0.005]. The hFH men constituted a
      heterogeneous group regarding their TG response to the fatty meal compared with
      healthy men because 50% with higher, but nevertheless 'normal' basal TG levels,
      had an abnormal post-prandial TG response. The reduced activity of low-density
      lipoprotein receptors in hFH together with other defects in TG handling may
      explain the abnormal rise of TG levels post-prandially.

PMID- 15857329
TI  - Levels of serum vitamin A, alpha-tocopherol and malondialdehyde in patients with
      non-alcoholic steatohepatitis: relationship with histopathologic severity.
AB  - The aims of our study were to estimate serum levels of malondialdehyde (MDA),
      serum levels of vitamin A and alpha-tocopherol as antioxidants and determine
      relationship of these with histopathologic severity in patients with non
      alcoholic steatohepatitis (NASH). Twenty-nine patients with biopsy-proven NASH
      were included to study. NASH were histopathologically scored for grading and
      staging. Serum MDA and vitamin A levels were increased in patients with NASH and
      simple steatosis as compared to healthy control group. Serum alpha-tocopherol
      levels measured in simple steatosis and NASH were significantly lower than in
      healthy control group. There was no significant difference between grade/stage 0
      1 and grade/stage 2-3 in terms of MDA, vitamin A and alpha-tocopherol levels.
      Serum MDA and vitamin A levels are increased in simple steatosis and NASH. MDA,
      vitamin A and alpha-tocopherol levels in NASH were not associated with the
      histopathologic severity.

PMID- 15857330
TI  - The transition from medical student to doctor: perceptions of final year students
      and preregistration house officers related to expected learning outcomes.
AB  - In this prospective qualitative study over 12 months, we evaluated the
      educational and clinical effectiveness of a new final year undergraduate
      programme in a London medical school (Guy's, King's and St Thomas'). A stratified
      sample of 17/360 final year students were interviewed four times, and the content
      was assessed against 32 amalgamated learning outcomes identified in 1997 in The
      New Doctor. At the beginning of the preregistration year, eight of the learning
      outcomes were already met, 10 partly, eight remained to be attained and for six,
      insufficient evidence existed. Preregistration house officers who have been
      through the final year student house officer programme expressed competence in
      many of the outcomes of the General Medical Council's New Doctor. The study
      identified areas such as prescribing where further developments are needed and
      will help in planning the new foundation programme.

PMID- 15857331
TI  - Microalbuminuria in Hodgkin's disease.
AB  - In some malignant disorders, it was reported that urinary albumin excretion (UAE)
      was correlated with the prognosis and the extent of the disease. In this study,
      24-h UAE was determined in 34 Hodgkin's disease patients without prior treatment
      and 19 healthy controls. Microalbuminuria (MAU) was defined as UAE > or = 20
      microg/min. In patients with MAU, UAE was determined again after the treatment.
      Mean UAE was 31.2 microg/min in the patient group and 5.6 microg/min in the
      controls (p = 0.005). Whereas MAU frequency was 47% in the patients, there was no
      MAU in the controls. Mean UAE tended to be higher in advanced stage patients
      compared to early stage patients (p = 0.051). Also, MAU frequency tended to be
      higher in the advanced stage group compared to the early stage group (p = 0.196).
      In four patients in whom remission could not have been achieved, although UAE was
      reduced, MAU did not disappear. In conclusion, UAE was increased in Hodgkin's
      disease. However, there is no significant correlation between UAE and the disease
      extent.

PMID- 15857332
TI  - Mechanisms and pattern of facial lacerations in the Accident Department.
AB  - The purpose of this study was to determine patterns of facial laceration seen in
      the Accident and Emergency Department and identify how they are related to the
      mechanism of injury. A retrospective analysis of facial lacerations of an adult
      presenting to Accident and Emergency department was made over a 6-month period.
      There were 197 consecutive facial lacerations. The mean age of patients was 46
      years. There were 137 male and 60 female patients. The aetiology of lacerations
      was falls (48%), assaults (11%), hit by an object by accident (21%) and hit
      stationary object by accident (15%). Mechanism of injury was found to be related
      to common patterns of laceration. Lacerations affecting the forehead mainly
      occurred in falls and those affecting the peri-orbital and peri-oral areas in
      assault. Lacerations were mainly linear, with a mean length of 2.4 cm, and about
      75% were precipitated by blunt injury. Identification of common patterns of
      injury corresponding to a certain mechanism may allow assessment of the difficult
      or non-compliant patient. Understanding mechanisms of injury will allow safety
      planners to design safer domestic and workplace environments.

PMID- 15857333
TI  - Neonatal screening for congenital hypothyroidism in West Black Sea area, Turkey.
AB  - The aim of this study was to investigate the incidence of congenital
      hypothyroidism (CH) in the West Black Sea Area, a mild-to-moderate iodine
      deficient area in Turkey. Neonatal screening for CH was performed using blood
      specimens collected onto filter paper. Thyrotropin [thyroid-stimulating hormone
      (TSH)] was measured by radioimmunoassay, and a value >20 microU/ml was considered
      as cut-off point for re-examining. Venous serum was obtained to measure TSH,
      thyroxin (T4), free T4 (FT4) and thyroglobulin (TG). To determine the iodine
      status of the study area, median urinary iodine was measured in 212 randomly
      selected neonates and their mothers. A total of 18606 neonates were screened from
      three cities (Bolu, Duzce, and Zonguldak) between 2000 and 2002. With a cut-off
      point of TSH value >20 microU/ml, the recall rate was found 1.6%. Eight cases of
      CH were diagnosed (incidence 1/2326). There were three cases of transient
      hypothyroidism, with an incidence of 1/6202. Twenty-six percent of the TSH values
      was greater than 5 microU/ml. Median urinary iodine concentrations in neonates
      and their mothers were 85 microg/l and 40 microg/l, respectively. The incidences
      of CH, transient hypothyroidism and the recall rate were higher in our study area
      than many countries in Europe. The study area has been affected by mild-to
      moderate iodine deficiency. Neonatal screening for CH should be introduced in
      Turkey without delay. A national comprehensive infantile hypothyroidism and
      iodine prophylaxis policies should be developed.

PMID- 15857334
TI  - Clinical assessment alone will not benefit patients with coronary heart disease:
      failure to achieve cholesterol targets in 12,045 patients--the Healthwise II
      study.
AB  - Healthwise II, a nurse-led audit programme in primary care during 1999-2002,
      assessed the uptake of secondary preventative measures for coronary heart disease
      (CHD). Risk factors, cardiovascular medications and blood cholesterol were
      recorded; 'at risk' patients were invited for a review after 6 months. Of 17,570
      patients assessed, CHD was clinically present in 12,045 (69%); in these, aspirin
      usage was high (78%) but fewer patients were on a beta-blocker (40%), angiotensin
      converting enzyme inhibitor (27%) or statin (49%). Blood pressure (BP) was
      controlled (<140/90) in only 41% of patients. Total cholesterol was >5 mmol/l in
      49% of all CHD patients, half of whom were taking a statin. In the statin users,
      total cholesterol was uncontrolled (>5 mmol/l) in 38%. At follow-up, BP control
      remained at 42%, statin use increased to 57% and cholesterol remained elevated in
      46%. Simple assessment in an audit programme fails to trigger change, and risk
      factor modification for CHD remains inadequate.

PMID- 15857335
TI  - Clinical manifestations and complications of gastroesophageal reflux disease
      (GERD).
AB  - Gastroesophageal reflux-induced diseases are among the most common disorders and
      are associated with classical oesophageal manifestations of gastroesophageal
      reflux disease (GERD) including a range of symptoms such as heartburn, acid
      regurgitation and chest pain, and also organic manifestations such as
      oesophagitis, oesophageal strictures and ulcerations, Barrett's oesophagus and
      oesophageal adenocarcinoma. Recognition of its impact on other organ systems,
      extra-oesophageal reflux diseases, such as the ear, nose and throat (ENT) region
      and the bronchopulmonary system, as well as its contribution to symptoms such as
      chest pain and sleep disturbances, is also increasing. This paper addresses the
      symptoms, diseases and complications in which the abnormal reflux of gastric
      content to the oesophagus and adjacent organ systems is believed to be a frequent
      contributory factor.

PMID- 15857336
TI  - Eosinophilic cystitis and its management.
AB  - Eosinophilic cystitis (EC) is a rare clinicopathological condition characterized
      by transmural inflammation of the bladder predominantly with eosinophils,
      associated with fibrosis with or without muscle necrosis. The cause of EC remains
      unclear, although it has been associated with various aetiological factors, such
      as allergy, bladder tumour, bladder trauma, parasitic infections and
      chemotherapeutic agents. EC is, probably, caused by the antigen-antibody
      reaction. This leads to the production of various immunoglobulins, which, in
      turn, cause the activation of eosinophils and initiates the inflammatory process.
      The most common symptom complex consists of frequency, haematuria, dysuria and
      suprapubic pain. Cystoscopy and biopsy are the gold standard for diagnosis.
      Additional laboratory evidence supporting the diagnosis includes proteinuria,
      microscopic haematuria and peripheral eosinophilia, the last one occurring in few
      patients. There is no curative treatment for this condition. Current treatment
      modalities include transurethral resection of the bladder lesion along with non
      specific medical therapy, such as non-steroidal anti-inflammatory agents or
      steroids. Because the lesion tends to recur in spite of the above therapy, long
      term follow-up is mandatory.

PMID- 15857337
TI  - The epidemiological aspects of irritable bowel syndrome in Southeastern Anatolia:
      a stratified randomised community-based study.
AB  - Even though studies on the epidemiology of the irritable bowel syndrome (IBS) are
      increasing day by day, epidemiological data are still unknown in many regions.
      Our objective was to determine the IBS prevalence, factors associated with this
      prevalence and probable risk groups in Southeastern Anatolia. The total
      population in the target region is approximately 6 million. A total of 3000
      people (1521 females and 1479 males) randomly selected by stratified cluster
      sampling were interviewed face-to-face by using a questionnaire comprising
      demographic features and the Rome II criteria which also included probable risk
      factors and questions related with Bristol scale stool form. The statistical
      analysis was performed by using a package program called EPI INFO 2000. IBS
      prevalence was 10.2% according to the Rome II criteria in our region. Six hundred
      and twenty-five of 3000 subjects had gastrointestinal symptoms in the last 3
      months. IBS rate was higher in women (12.4%) than in men (8.0%), and married
      subjects had higher IBS rates (11.6%) than singles (6.7%). Those differences were
      statistically significant (p = 0.000 for both). It was most common in the 35-54
      year age group. No difference was observed in terms of settlement (rural/urban),
      age group, education and occupation. History of abortion in women increased the
      IBS risk by 1.8 times (p = 0.000 Crude odds ratios = 1.8 (1.3-2.6) 95% confidence
      intervals). Of the IBS patients, 48.1% had characteristics of diarrhoea
      predominance, 38.9% constipation-predominance while 13.0% had none. There was a
      significant relation between dominant stool form and Bristol scale stool form.
      IBS prevalence is 10.2% in the first community-based study carried out in this
      specific subject in Southeastern Anatolia. The dominance of middle age and
      females remained significant.

PMID- 15857338
TI  - An insidious preauricular sinus presenting as an infected postauricular cyst.
AB  - Preauricular sinuses are common congenital malformations that usually occur at
      the anterior margin of the ascending limb of the helix. We present three
      paediatric patients with postauricular infected cysts and coincidentally
      discovered auricular pits. Single-stage operations were performed to remove the
      cysts, pits and involved cartilage. Histopathology revealed a preauricular sinus
      with inflammation. Although uncommon, a postauricular infected cyst may indicate
      the presence of a preauricular sinus. Detailed physical examination of
      preauricular pits should be performed, and the operating microscope may aid
      during surgery to remove remnants and prevent recurrence. An infected
      preauricular sinus can be effectively treated with single-stage excision.

PMID- 15857339
TI  - Association between Wegener's granulomatosis and increased antithyroid
      antibodies: report of two cases and review of the literature.
AB  - We report two patients with severe manifestations of Wegener's granulomatosis,
      who also had significantly increased antithyroid antibodies. Auto-immune reaction
      against various human tissue antigens probably explains the association between
      increased anti-neutrophil cytoplasmic and antithyroid antibodies. The clinicians
      should include thyroid function and antithyroid antibody tests in the laboratory
      work up of the patients with Wegener's granulomatosis.

PMID- 15857340
TI  - Acute myocardial infarction and rescue percutaneous transluminal coronary
      angioplasty in a young HIV-infected patient.
AB  - We report a case of acute myocardial infarction in an HIV-infected patient
      without significant coronary artery disease (CAD) risk factors. The patient
      underwent rescue percutaneous transluminal coronary angioplasty (PTCA), with a
      successful outcome. We presume a possible pathogenetic role of anti-retroviral
      therapy and/or direct viral action on ischaemic heart disease progression. We
      propose that the current approach to management of AIDS-affected patients needs
      close monitoring for CAD risk factors and symptoms, to improve prognosis and life
      expectancy.

PMID- 15857342
TI  - Erectile dysfunction, like diabetes, should be considered a 'cardiovascular
      equivalent'.

PMID- 15857343
TI  - The European working time directive: implications for subspecialty acute care.
AB  - The requirements of the new deal for junior doctors' hours has meant that many
      smaller trusts are unable to provide adequate cover on-call for medical and
      surgical subspecialties. The care of the acute subspecialty patients has,
      therefore, shifted to general teams in many trusts. We assessed what impact this
      had upon the outcome of acute urological cases in our district general hospital
      by prospectively monitoring acute renal colic admissions over a 12-month period
      and surveyed the provision of services in other regional hospitals. The shift in
      care of the acute urological patient was associated with considerable morbidity
      for patients admitted in our hospital. The additional financial burden due to
      this morbidity was estimated to be 33000 pounds/annum. The implementation of the
      new deal must be achieved with every care to minimise the clinical and financial
      costs of withdrawing acute subspecialty services.

PMID- 15857344
TI  - Prescribing pattern in Parkinson's disease: are cost and efficacy overriding
      factors?
AB  - Information on prescribing pattern of antiparkinsonian medications and factors
      influencing neurologists' choice of such drugs are important considerations in
      evaluating healthcare cost of Parkinson's disease (PD). We surveyed neurologists'
      perceived factors influencing their choice of drugs and actual prescribing
      pattern in PD. Three hundred and six patients at a tertiary hospital, diagnosed
      with idiopathic PD and who were dispensed antiparkinsonian drugs during a 6-month
      period were randomly selected. Patient demographics, type and dose of medications
      were analysed. A questionnaire survey evaluating the factors influencing choice
      of medications was administered to neurologists who practiced at the institution.
      The study population had a mean age of 64.4 years (SD +/- 9.9 years), and more
      than 80% were at Hoehn & Yahr stage 2-3. 92.3% of the study population were
      receiving levodopa and monotherapy, with levodopa being the most common treatment
      regimen. Patients who were prescribed levodopa were significantly older and at a
      later stage of disease compared to those without levodopa (p < 0.05). Only 26.8%
      of patients were prescribed dopamine agonists. In the survey, the neurologists
      cited severity of symptoms, and patients' intolerance of side effects, and
      efficacy as the most important factors influencing their choice of drugs.
      However, the actual prescribing pattern revealed a strong positive correlation of
      drug usage with cost subsidy by the institution. While factors affecting drug
      usage in PD are well recognised, cost and efficacy of a drug appear to be
      overriding practical factors in influencing usage pattern in clinical practice.

PMID- 15857345
TI  - Examination of anxiety, hostility and psychiatric disorders in patients with
      migraine and tension-type headache.
AB  - The role of psychological factors related to headache has long been a focus of
      investigation. The aim of this study was to evaluate anxiety, depression,
      hostility and psychological symptoms in patients with migraine and tension-type
      headache (TTH) and to compare the results with healthy controls. Seventy-five
      subjects with migraine and 55 subjects with TTH (according to the criteria of the
      International Headache Society classification) and a control group including 73
      healthy subjects were studied. The Buss-Durkee Hostility Inventory, Brief Symptom
      Inventory, State-trait Anxiety Inventory, Trait form were administered to the
      subjects. Compared with healthy controls, the patients with headache had
      significantly higher scores on measures of anxiety, depression and hostility and
      lower scores on psychological symptoms. The present results indicate the need to
      distinguish the unique dimensions of anxiety, depression and hostility that
      should be assessed in the population with headaches.

PMID- 15857346
TI  - Tension-free vaginal tape: avoiding failure.
AB  - A prospective, single-centre study to assess the outcome of incontinence surgery
      in the first 120 consecutive patients who had tension-free vaginal tape (TVT) by
      a single surgeon. All patients were initially seen at 3 months postsurgery, with
      a cough provocation test, measurement of residual urine volume and a satisfaction
      survey. At a mean of 26 months (6-42 months) after surgery, a validated telephone
      interview was performed. The operation was performed in accordance with the
      original technique described by Ulmsten et al. [Int Urogynecol J Pelvic Floor
      Dysfunct 1996; 7: 81-5]. A total of 87 of 120 patients completed the study with
      the others either not complying or having died. Sixty-three (72.4%) patients were
      completely dry on cough provocation test. Of these, four (4.5%) had a slow stream
      and 10 (11.4%) suffered persistent urgency. The remaining 24 patients had varying
      degrees of leakage (operative failure). Sixteen (18.3%) patients subjectively
      considered the procedure to have failed at 3 months follow-up, either because
      leakage occurred once or more a day, and/or the persistence of the preoperative
      frequency/urgency syndrome. Of these 16 TVT failures, two had previous pelvic
      radiotherapy, two had double incontinence and eight had TVT for recurrent
      incontinence. Among the failures, 81.3% had mixed incontinence with predominant
      urge and nocturia three times per twenty four hours. Our study highlights the
      need for selection when performing TVT. We recommend that TVT be performed for
      those who have simple stress incontinence failing conservative measures (pelvic
      floor exercises and physiotherapy), with no history of incontinence surgery,
      pelvic radiotherapy, faecal or mixed incontinence.

PMID- 15857347
TI  - Patients' preference for gender of urologist.
AB  - The NHS Plan is for a health service designed around the patient. Several studies
      have investigated patients' preference for the gender of their doctor. However,
      within these studies, the patients have predominantly been females. The
      preferences of urology patients, of whom the majority are males, have not
      previously been investigated. The preferences for gender of urologist, from 496
      consecutive patients attending urology clinic in a district general hospital,
      were investigated by questionnaires. The majority of patients had no preference
      for gender of their urologist. Of the patients who did have a preference, females
      were more likely to prefer the same gender urologist than males.

PMID- 15857348
TI  - The comparative investigation of morphology of papillary muscles of left
      ventricle in different species.
AB  - The papillary muscles of the heart are conical projections into the respective
      chamber of myocardium covered by endocardium. Functionally, the papillary muscles
      are important part of the respective valve complex. They prevent the cusps of a
      valve from being everted when the ventricle contracts. Our study was conducted on
      papillary muscles in left ventricle of 135 normal adult hearts (20 humans, 25
      dogs, 60 sheep and 30 goats). The length (L), width (W), head number (HN), angle
      with ventricular wall (A degrees ), distance with annulus (AnD) and apex (ApD),
      and the shapes of the anterior and posterior papillary muscles were observed. The
      tendinous chords (CTN) attached to each papillary muscle were counted at their
      origin. The values of both anterior and posterior papillary muscles were not
      statistically significant (p > 0.05) in measurements of L, W, HN, A degrees and
      AnD of all species, but those of CTN and ApD were significant (p < 0.05) between
      human and animal hearts, while the difference was not significant (p > 0.05)
      between sheep and goat hearts. Knowledge of morphology of papillary muscles in
      different species will be of much use to clinical investigators in their studies.

PMID- 15857349
TI  - Therapy, outcome and analysis of c-kit expression in patients with extrapulmonary
      small cell carcinoma.
AB  - In this study, we aimed to investigate the clinicopathological characteristics
      with special emphasis on c-kit expression and the treatment results of patients
      with extrapulmonary small cell carcinoma (EPSCC). The medical records of the
      patients with EPSCC were reviewed, and the data regarding patient and tumour
      characteristics, treatment and clinical outcome were retrieved and analysed. A
      total of 28 patients with the diagnosis of EPSCC were identified. There were 19
      males and 9 females, with a mean age of 56.5 years. Patients with limited disease
      (LD) (n = 13) were treated with surgery, chemotherapy (CT) and radiotherapy with
      different sequences. Patients with extensive disease (ED) (n = 15) were mainly
      treated with combination CT. The median overall survival was 14.5 months in
      patients with LD compared to 11 months in those with ED (p = 0.029). Ten patients
      (36%) showed c-kit overexpression. There was no significant difference between
      the survival of c-kit-positive and c-kit-negative patients (p = 0.367). In
      conclusion, our study demonstrates that the prognosis of EPSCC is poor despite
      currently available treatments. C-kit may be considered as a potential target for
      novel therapeutical approaches.

PMID- 15857350
TI  - Does carboxymethylcellulose have a role in reducing time to full enteral feeds in
      preterm neonates?
AB  - The efficacy of prophylactic carboxymethylcellulose (CMC) in reducing the time to
      reach full enteral feeds (FEFs) in neonates <32 weeks' gestation was studied in a
      clinical trial. When ready for feeds, enrolled neonates were allocated to either
      CMC (dose: CMC content of 12 mg oral erythromycin ethyl succinate syrup, 6
      hourly) or placebo till either maximum 10 days treatment or FEF (150 ml/kg/day)
      was reached. A standardised regimen guided enteral feeding. Demographic
      characteristics of enrolled neonates (CMC, placebo: n = 35) were comparable.
      Median (interquartile range) gestational age and birth weight were 29 (28, 30)
      vs. 29 (27, 31) weeks and 1090 (905, 1390) vs. 1236 g (928, 1565) for the CMC and
      placebo groups, respectively. Median (interquartile range) time to reach FEF was
      5 (4, 6) vs. 5 (3, 8) days for CMC and placebo group, respectively (p = 0.5). No
      CMC-related adverse effects occurred. Prophylactic CMC did not have a significant
      role in reducing time to reach FEF.

PMID- 15857351
TI  - Clinical experience in managing Fusarium solani keratitis.
AB  - Fusarium solani keratitis is a rare ocular infectious disease. The clinical
      characteristics and treatment methods of 18 patients with culture proven F.
      solani keratitis between July 1997 and December 2003 and with a follow-up period
      of more than 4 months were analysed retrospectively. The patients were divided
      into two groups based on the severity of keratitis. Group A (n = 13) displayed
      non-severe keratitis and were treated with debridement, lamellar keratectomy and
      antifungal medication. Group B (n = 5) displayed severe keratomycosis and were
      treated with lamellar keratectomy combined with amniotic membrane transplantation
      (AMT) and antifungal medication. In group A, wound healing did not interfere with
      the integrity of the anterior chamber. The mean re-epithelialisation time was
      12.67 days (range: 5-21 days). All patients were free of major immediate
      postoperative complications. In group B, AMT preserved the anterior chamber
      integrity in two cases, but failed to do so in the other three cases. Therapeutic
      patch grafts were required in these three cases. Non-severe F. solani keratitis
      is best treated with superficial keratectomy. Timely AMT combined with lamellar
      keratectomy appears to be an adjuvant therapy for severe keratomycosis and
      avoiding emergent therapeutic penetrating keratoplasty. However, AMT was
      effective in cases involving non-suppurative Fusarium keratitis.

PMID- 15857352
TI  - Venous thromboembolism in the medically ill patient: a call to action.
AB  - The risk of venous thromboembolism (VTE) in medical patients is generally
      underestimated. However, recent studies including two large double-blind placebo
      controlled trials, the Prospective Evaluation of Dalteparin Efficacy for
      Prevention of VTE in Immobilised Patients trial (PREVENT) and prophylaxis in
      MEDical patients with ENOXaparin, study show that low-molecular-weight heparins
      (LMWHs) provide effective thromboprophylaxis for medical patients at risk from
      VTE without increasing the risk of bleeding. In PREVENT the significant 45%,
      reduction in VTE among patients receiving dalteparin 5000 IU once daily for 14
      days was attributed entirely to a reduction in clinically relevant VTE. The
      recently published guidelines for the prevention and treatment of VTE, issued by
      the American College of Chest Physicians, recommend prophylaxis with LMWHs (or
      low-dose unfractionated heparin) in acutely ill medical patients with risk
      factors for VTE (grade 1A). Current evidence should encourage the more widespread
      adoption of thromboprophylaxis in at-risk medical patients, and thus reduce the
      number of preventable deaths and complications due to VTE.

PMID- 15857353
TI  - Withdrawal syndrome following cessation of antihypertensive drug therapy.
AB  - In this study, a review of the available information concerning abrupt withdrawal
      of antihypertensive drug therapy is presented. Abrupt withdrawal of these drugs
      can produce a syndrome of sympathetic overactivity that includes nervousness,
      tachycardia, headache, agitation and nausea 36-72 h after cessation of the drug.
      A withdrawal syndrome may occur after discontinuation of almost all types of
      antihypertensive drugs, but mostly occurs with clonidine, beta-blockers,
      methyldopa and guanabenz. Less commonly can produce a rapid increase of the blood
      pressure to pre-treatment levels or above, or both and/or myocardial ischaemia.
      Although the exact incidence of the syndrome is not known, it appears to be rare,
      at least in patients receiving standard doses of the above antihypertensive
      drugs. The best treatment is prevention. In this study regarding the withdrawal
      syndrome that follows cessation of antihypertensive drugs therapy, a reference to
      the abrupt discontinuation of the main categories of antihypertensive drugs is
      also attempted.

PMID- 15857354
TI  - A review of the current evidence for the use of angiotensin-receptor blockers in
      chronic heart failure.
AB  - Angiotensin-converting enzyme (ACE) inhibitors have a central role in the
      management of heart failure, reflecting the contribution of the renin-angiotensin
      aldosterone system to the pathophysiology of the condition. Angiotensin-receptor
      blockers (ARBs) bind specifically to the angiotensin type 1 receptor and may
      offer further benefits compared with ACE inhibitors. Candesartan, losartan and
      valsartan have all been evaluated in large clinical outcome trials in heart
      failure. They display marked differences in pharmacokinetics and receptor-binding
      properties that may contribute to observed differences in outcome. ELITE II found
      no significant difference in outcome with losartan as compared with captopril. In
      the Val-Heft trial, valsartan reduced heart failure hospitalisations when added
      to conventional therapy including an ACE inhibitor in most patients, but had no
      effect on mortality. The CHARM programme showed that candesartan reduced
      morbidity and mortality in heart failure with reduced systolic function, both
      when added to ACE inhibitor therapy or when used as an alternative in patients
      who are intolerant to ACE inhibitors. Moreover, the CHARM-preserved study
      suggested that candesartan is beneficial in patients with heart failure and
      preserved left-ventricular systolic function. A growing body of evidence show
      that ARBs are an important contribution to the pharmaceutical management of
      patients with heart failure.

PMID- 15857355
TI  - Enlarging the scope of managing benign prostatic hyperplasia: addressing sexual
      function and quality of life.
AB  - Benign prostatic hyperplasia is a common genitourinary disorder that increases in
      incidence with age. Symptoms of this condition include a weak urinary stream,
      hesitancy, intermittency and sensations of incomplete emptying, as well as
      frequency, urgency, urge incontinence and nocturia. These symptoms can be
      ameliorated successfully by a variety of medical treatments - such as alpha(1)
      adrenergic blockade and 5-alpha-reductase inhibition - and surgical therapies -
      including transurethral resection of the prostate and less-invasive procedures.
      However, many of the treatments are known to result in sexual dysfunction, which
      can have a negative impact on the patient's quality of life. This must be
      considered when the physician seeks to determine the appropriate treatment for an
      individual patient. Current reports suggest that alpha(1)-adrenergic blockade is
      most likely to improve lower urinary tract symptoms while resulting in the fewest
      sexual side-effects; 5-alpha-reductase inhibitors appear to be particularly
      appropriate in men with large prostates. Among surgical therapies, transurethral
      resection of the prostate remains the gold standard, but is associated with a
      high incidence of sexual side-effects, especially retrograde ejaculation.
      Transurethral incision of the prostate, which is an endoscopic procedure, may be
      as effective as transurethral resection, but results in fewer side-effects.
      Minimally invasive procedures, including laser ablation or resection of the
      prostate, transurethral microwave thermotherapy and transurethral needle
      ablation, are rapidly evolving technologies that have demonstrated promising
      results, at least in the short term.

PMID- 15857356
TI  - Treatment options for paraphimosis.
AB  - Paraphimosis is a frequently presented complaint in the emergency department.
      This review outlines the treatment options available for resolving this
      condition: manual reduction methods, osmotic methods, puncture and aspiration
      methods and treatments using sharp incision. The technique of penile block local
      anaesthesia is described. A technique sequence for treatment is suggested.

PMID- 15857357
TI  - Emergency treatment of acute attacks in hereditary angioedema due to C1 inhibitor
      deficiency: what is the evidence?
AB  - Hereditary angioedema (HAE) is caused by a deficiency in C1 esterase-inhibitor
      (C1-INH) and is characterised by skin swelling, abdominal pain and episodes of
      upper respiratory tract obstruction. Oedema of the larynx can result in rapid
      asphyxiation and requires emergency treatment. Three treatment options for
      emergency treatment of HAE are reviewed: fresh frozen plasma, solvent/detergent
      treated plasma and C1-INH concentrate. It is concluded that while all three
      treatment options are theoretically effective in the emergency treatment of HAE,
      C1-INH is the treatment of choice.

PMID- 15857358
TI  - Perindopril: the reasonable choice in patients with coronary artery disease.
AB  - Recent studies in patients with coronary artery disease (CAD) have suggested that
      angiotensin-converting enzyme (ACE) inhibitors may have benefits beyond blood
      pressure reduction alone. Increased arterial stiffness, itself an emerging risk
      factor for CAD, adversely influences ventricular vascular interaction, leading to
      an increased central aortic pulse pressure. A number of recent studies have
      demonstrated a clear relationship between central pulse pressure and angiographic
      CAD. Furthermore, aortic stiffness also correlates with CAD. These studies are
      consistent with the hypothesis that central aortic stiffness may promote the
      development of CAD and that therapeutic intervention targeted at reducing
      arterial stiffness may be of benefit in patients with CAD. The ACE inhibitor,
      perindopril, has been shown to decrease arterial stiffness, largely independently
      of any effect on peripheral blood pressure. Results of the recent REASON study
      demonstrate that perindopril, in combination with indapamide, reduces central
      systolic and pulse pressure to a greater degree than the beta-blocker atenolol
      and that this effect is due to improved arterial stiffness and decreased wave
      reflection. In addition to its other beneficial effects, such as improved
      endothelial function and decreased inflammation, these haemodynamic effects of
      perindopril may therefore have contributed to the decrease in cardiovascular
      events seen in patients in the EUROPA study. Overall, perindopril, in addition to
      lowering peripheral blood pressure, decreases arterial stiffness and central
      pulse pressure. In individuals with CAD, perindopril would thus appear to be a
      very reasonable choice.

PMID- 15857359
TI  - Are we good at thromboembolic disease prophylaxis - an audit of the use of risk
      assessment forms in emergency medical admissions.
AB  - Venous thromboembolism (VTE) is a major cause of morbidity and mortality in
      hospitalised patients. Thromboprophylaxis is an effective strategy for VTE
      prevention in high-risk patients. An initial audit in our district general
      hospital trust showed poor adherence to the thromboembolic risk factors consensus
      group recommendations and so a risk assessment form (RAF) was devised. We present
      repeated audits to assess the RAF uptake and its effects on VTE
      thromboprophylaxis. We also present data analysing perceptions among doctors of
      the RAF and reasons for its poor completion. We provide compelling evidence that
      the RAF is an invaluable tool in the assessment of VTE thromboprophylaxis.

PMID- 15857360
TI  - PIP syndrome: a potentially threatening manifestation of a psychiatric disorder.

PMID- 15857361
TI  - Mycotic aneurysm of the superior mesenteric artery in a young woman.
AB  - Aneurysm of the superior mesenteric artery (SMA) is rare. We, in this study,
      present the case of a 21-year-old woman with a history of heroin abuse who was
      admitted to our hospital for infective endocarditis complicated by floating
      vegetation at the posterior mitral valve. After receiving 2-week antibiotic
      treatment, the patient had acute abdominal pain. Computed tomography demonstrated
      an aneurysm at the SMA. The mycotic aneurysm was resected and the mitral valve
      was repaired successfully. This report reviews the pathophysiology of mycotic
      aneurysms of the SMA and role of computed tomography in the differential
      diagnosis of this condition from acute mesenteric ischaemia.

PMID- 15857362
TI  - Endoplasmic reticulum positioning and partitioning in mitotic HeLa cells.
AB  - Cell division serves to distribute chromosomes and organelles into two daughter
      cells, but the mechanism of rough endoplasmic reticulum (RER) segregation in
      animal cell mitosis is poorly understood. Here we study the distribution of RER
      in mitotic HeLa cells and its relation to the cytoskeleton. At metaphase, the RER
      was located in the cell cortex and was most concentrated in two locations. Close
      to the plasma membrane the RER was closely associated with cortical actin, and
      after treatment with Latrunculin A RER elements retracted to the deep cortex and
      became more tubular. Positioning was therefore dependent on cortical F-actin.
      Deeper in the cortex cisternae were wrapped tightly around the contours of the
      spindle body and orientated along microtubules close the spindle poles.
      Stereology revealed a close correlation between RER volume and cell volume in
      telophase daughter cells. These results suggest that the RER is positioned at the
      outer and inner regions of metaphase cortex by association with cytoskeleton.
      This arrangement combined with a disposition in concentric layers, deep to the
      plasma membrane, appears to distribute the RER evenly in the cortex and may help
      to couple quantities of RER and cell constituents.

PMID- 15857363
TI  - A segmental pattern of alkaline phosphatase activity within the notochord
      coincides with the initial formation of the vertebral bodies.
AB  - This study shows that segmental expression of alkaline phosphatase (ALP) activity
      by the notochord of the Atlantic salmon (Salmo salar L.) coincides with the
      initial mineralization of the vertebral body (chordacentrum), and precedes ALP
      expression by presumed somite-derived cells external to the notochordal sheath.
      The early expression of ALP indicates that the notochord plays an instructive
      role in the segmental patterning of the vertebral column. The chordacentra form
      segmentally as mineralized rings within the notochordal sheath, and ALP activity
      spreads within the chordoblast layer from ventral to dorsal, displaying the same
      progression and spatial distribution as the mineralization process. No ALP
      activity was observed in sclerotomal mesenchyme surrounding the notochordal
      sheath during initial formation of the chordacentra. Our results support previous
      findings indicating that the chordoblasts initiate a segmental differentiation of
      the notochordal sheath into chordacentra and intervertebral regions.

PMID- 15857364
TI  - Twist is required for establishment of the mouse coronal suture.
AB  - Cranial sutures are the growth centres of the skull, enabling expansion of the
      skull to accommodate rapid growth of the brain. Haploinsufficiency of the human
      TWIST gene function causes the craniosynostosis syndrome, Saethre-Chotzen
      syndrome (SCS), in which premature fusion of the coronal suture is a
      characteristic feature. Previous studies have indicated that Twist is expressed
      in the coronal suture during development, and therefore that it may play an
      important role in development and maintenance of the suture. The Twist-null mouse
      is lethal before the onset of osteogenesis, and the heterozygote exhibits coronal
      suture synostosis postnatally. In this study we investigated the function of
      Twist in the development of the mouse coronal suture, by inhibiting Twist
      synthesis using morpholino antisense oligonucleotides in calvarial organ culture.
      Decreased Twist production resulted in a narrow sutural space and fusion of bone
      domains within 48 h after the addition of the morpholino oligonucleotides.
      Proliferation activity in the sutural cells was decreased, and the expression of
      osteogenic marker genes such as Runx2 and Fgfr2 was up-regulated in the
      developing bone domain within 4 h. These results suggest that during
      establishment of the suture area, Twist is required for the regulation of sutural
      cell proliferation and osteoblast differentiation.

PMID- 15857365
TI  - Relationship between bone growth rate and the thickness of calcified cartilage in
      the long bones of the Galloanserae (Aves).
AB  - The histological features of mineralized tissues can be preserved for hundreds of
      millions of years, and are therefore important potential sources of information
      for reconstructing the life history traits of extinct species. Bone growth rates
      and the duration of the growth period have recently been estimated in fossil
      archosaurs from periosteal ossification (a mechanism responsible for bone
      diametral growth). Similarly, data on endochondral ossification (the mechanism
      responsible for bone longitudinal growth) may also yield information on growth
      duration and rate among extinct vertebrates, as long as potentially informative
      structures are preserved. However, in order to carry out palaeobiological
      estimations of growth rate and/or the duration of growth, it is first necessary
      to quantify in extant species the relationship between these life history traits
      and the histological features of endochondral ossification that are potentially
      preserved in the fossil record. Here we analyse the ontogenetic variation of both
      bone longitudinal growth rate and the thickness of the calcified cartilage in the
      femora of two Galloanserae (Aves) and find a significant positive relationship
      between these variables in both species. We discuss possible factors underlying
      interspecific differences in this relationship, and conclude that it could be
      applied with caution to draw palaeobiological inferences.

PMID- 15857366
TI  - Functional analysis of the foot and ankle myology of gibbons and bonobos.
AB  - This study investigates the foot and ankle myology of gibbons and bonobos, and
      compares it with the human foot. Gibbons and bonobos are both highly arboreal
      species, yet they have a different locomotor behaviour. Gibbon locomotion is
      almost exclusively arboreal and is characterized by speed and mobility, whereas
      bonobo locomotion entails some terrestrial knuckle-walking and both mobility and
      stability are important. We examine if these differences in locomotion are
      reflected in their foot myology. Therefore, we have executed detailed dissections
      of the lower hind limb of two bonobo and three gibbon cadavers. We took several
      measurements on the isolated muscles (mass, length, physiological cross sectional
      area, etc.) and calculated the relative muscle masses and belly lengths of the
      major muscle groups to make interspecific comparisons. An extensive description
      of all foot and ankle muscles is given and differences between gibbons, bonobos
      and humans are discussed. No major differences were found between the foot and
      ankle musculature of both apes; however, marked differences were found between
      the ape and human foot. The human foot is specialized for solely one type of
      locomotion, whereas ape feet are extremely adaptable to a wide variety of
      locomotor modes. Apart from providing interesting anatomical data, this study can
      also be helpful for the interpretation of fossil (pre)hominids.

PMID- 15857367
TI  - A 3D digital reconstruction of the components of the gas exchange tissue of the
      lung of the muscovy duck, Cairina moschata.
AB  - To elucidate the shape, size, and spatial arrangement and association of the
      terminal respiratory units of the avian lung, a three-dimensional (3D) computer
      aided voxel reconstruction was generated from serial plastic sections of the lung
      of the adult muscovy duck, Cairina moschata. The air capillaries (ACs) are rather
      rotund structures that interconnect via short, narrow passageways, and the blood
      capillaries (BCs) comprise proliferative segments of rather uniform dimensions.
      The ACs and BCs anastomose profusely and closely intertwine with each other,
      forming a complex network. The two sets of respiratory units are, however,
      absolutely not mirror images of each other, as has been claimed by some
      investigators. Historically, the terms 'air capillaries' and 'blood capillaries'
      were derived from observations that the exchange tissue of the avian lung mainly
      consisted of a network of minuscule air- and vascular units. The entrenched
      notion that the ACs are straight (non-branching), blind-ending tubules that
      project outwards from the parabronchial lumen and that the BCs are direct tubules
      that run inwards parallel to and in contact with the ACs is overly simplistic,
      misleading and incorrect. The exact architectural properties of the respiratory
      units of the avian lung need to be documented and applied in formulating reliable
      physiological models. A few ostensibly isolated ACs were identified. The
      mechanism through which such units form and their functional significance, if
      any, are currently unclear.

PMID- 15857370
TI  - An optical differential scanning calorimeter cryomicroscope.
AB  - An optical-DSC system was designed, built, tested, calibrated and verified to
      incorporate into a single device the capability for simultaneous optical
      cryomicroscopy and differential scanning calorimetry (DSC). This instrument can
      be used to obtain both visual and thermal data for an individual specimen
      subjected to a defined freezing and thawing protocol with very little compromise
      in quality or range of data available in comparison with dedicated single
      instruments. Temperature and caloric calibrations were performed based on phase
      transition states in water, n-dodecane and n-decane. The instrument has proven
      effective for process analysis in living cells and in foodstuffs.

PMID- 15857371
TI  - SEM examination of human erythrocytes in uncoated bloodstains on stone: use of
      conventional as environmental-like SEM in a soft biological tissue (and hard
      inorganic material).
AB  - Although nowadays the so-called environmental scanning electron microscopes
      (ESEMs) allow the observation of the samples without metal or carbon coating,
      many conventional scanning electron microscopes (SEMs) are still in use. On the
      other hand, the presence of erythrocytes (red blood cells, RBCs) in a smear is
      considered a blood confirmation. Such a presence has been previously reported
      even in Lower Stone Age implements. In previous works, I have reported several
      studies dealing with cytomorphology of RBCs in bloodstains using scanning
      electron microscopy with standard specimen preparation procedures, i.e. via
      coating the samples before SEM analysis. In order to explore the potential of
      conventional SEM as environmental-like SEM in haemotaphonomical studies, two
      alkaline (limestone) and two acid (flint) rock fragments were smeared with human
      blood from a male and a female. The bloodstains obtained in this way were then
      air dried indoors and stored into a non-hermetic plastic box. Afterwards, the
      smears and their rock substrates were examined directly without coating, via
      secondary electrons, using a JEOL JSM-6400 scanning electron microscope.
      Satisfactory results reveal the capability of a conventional SEM to work in
      secondary-electron mode as an environmental-like SEM on these kinds of biological
      and inorganic materials, and probably in many other biological and non-biological
      samples.

PMID- 15857372
TI  - Visualization of grain subdivision by analysing the misorientations within a
      grain using electron backscatter diffraction.
AB  - The misorientation relative to the average orientation of a grain and the point
      to-point relative misorientation along a line across a moderately cold deformed
      grain, calculated from an electron backscatter diffraction (EBSD) dataset, are
      analysed in detail by visualizing both the misorientation angle and the
      misorientation axis. The significance of monitoring the misorientation axis is
      illustrated by an example of a grain subdivided into a misorientation band
      structure. A new technique to visualize the subdivision structure by assigning
      colours to misorientations in such a way that the contrast is maximized within a
      grain is introduced and discussed. Furthermore, some methods for grain boundary
      reconstruction from EBSD datasets are compared with the map of the confidence
      index in order to provide a validation of the accuracy of these methods.

PMID- 15857373
TI  - Crystallographic analysis of thin specimens.
AB  - Electron backscattering diffraction (EBSD) is commonly used on bulk samples for
      crystallographic material characterization. In this work, the technique was
      applied on transmission electron microscopy (TEM)-type thin specimens, prepared
      with a focused ion beam. Orientation maps were successfully collected on
      specimens made of a Cu3Au copper-gold alloy. As compared to EBSD analysis on a
      bulk specimen, an improved pattern quality and a high spatial resolution (well
      below 10 nm) were obtained. Furthermore, a clear improvement of the signal-to
      noise ratio with decreasing sample thickness was observed.

PMID- 15857374
TI  - Automated alignment and pattern recognition of single-molecule force spectroscopy
      data.
AB  - Recently, direct measurements of forces stabilizing single proteins or individual
      receptor-ligand bonds became possible with ultra-sensitive force probe methods
      like the atomic force microscope (AFM). In force spectroscopy experiments using
      AFM, a single molecule or receptor-ligand pair is tethered between the tip of a
      micromachined cantilever and a supporting surface. While the molecule is
      stretched, forces are measured by the deflection of the cantilever and plotted
      against extension, yielding a force spectrum characteristic for each biomolecular
      system. In order to obtain statistically relevant results, several hundred to
      thousand single-molecule experiments have to be performed, each resulting in a
      unique force spectrum. We developed software and algorithms to analyse large
      numbers of force spectra. Our algorithms include the fitting polymer extension
      models to force peaks as well as the automatic alignment of spectra. The aligned
      spectra allowed recognition of patterns of peaks across different spectra. We
      demonstrate the capabilities of our software by analysing force spectra that were
      recorded by unfolding single transmembrane proteins such as bacteriorhodopsin and
      NhaA. Different unfolding pathways were detected by classifying peak patterns.
      Deviant spectra, e.g. those with no attachment or erratic peaks, can be easily
      identified. The software is based on the programming language C++, the GNU
      Scientific Library (GSL), the software WaveMetrics IGOR Pro and available open
      source at http://bioinformatics.org/fskit/.

PMID- 15857375
TI  - Porphyrin-related photosensitizers for cancer imaging and therapeutic
      applications.
AB  - A photosensitizer is defined as a chemical entity, which upon absorption of light
      induces a chemical or physical alteration of another chemical entity. Some
      photosensitizers are utilized therapeutically such as in photodynamic therapy
      (PDT) and for diagnosis of cancer (fluorescence diagnosis, FD). PDT is approved
      for several cancer indications and FD has recently been approved for diagnosis of
      bladder cancer. The photosensitizers used are in most cases based on the
      porphyrin structure. These photosensitizers generally accumulate in cancer
      tissues to a higher extent than in the surrounding tissues and their fluorescing
      properties may be utilized for cancer detection. The photosensitizers may be
      chemically synthesized or induced endogenously by an intermediate in heme
      synthesis, 5-aminolevulinic acid (5-ALA) or 5-ALA esters. The therapeutic effect
      is based on the formation of reactive oxygen species (ROS) upon activation of the
      photosensitizer by light. Singlet oxygen is assumed to be the most important ROS
      for the therapeutic outcome. The fluorescing properties of the photosensitizers
      can be used to evaluate their intracellular localization and treatment effects.
      Some photosensitizers localize intracellularly in endocytic vesicles and upon
      light exposure induce a release of the contents of these vesicles, including
      externally added macromolecules, into the cytosol. This is the basis for a novel
      method for macromolecule activation, named photochemical internalization (PCI).
      PCI has been shown to potentiate the biological activity of a large variety of
      macromolecules and other molecules that do not readily penetrate the plasma
      membrane, including type I ribosome-inactivating proteins, immunotoxins, gene
      encoding plasmids, adenovirus, peptide-nucleic acids and the chemotherapeutic
      drug bleomycin. The background and present status of PDT, FD and PCI are
      reviewed.

PMID- 15857376
TI  - Performance comparison between the high-speed Yokogawa spinning disc confocal
      system and single-point scanning confocal systems.
AB  - Fluorescence microscopy of the dynamics of living cells presents a special
      challenge to a microscope imaging system, simultaneously requiring both high
      spatial resolution and high temporal resolution, but with illumination levels low
      enough to prevent fluorophore damage and cytotoxicity. We have compared the high
      speed Yokogawa CSU10 spinning disc confocal system with several conventional
      single-point scanning confocal (SPSC) microscopes, using the relationship between
      image signal-to-noise ratio and fluorophore photobleaching as an index of system
      efficiency. These studies demonstrate that the efficiency of the CSU10
      consistently exceeds that of the SPSC systems. The high efficiency of the CSU10
      means that quality images can be collected with much lower levels of
      illumination; the CSU10 was capable of achieving the maximum signal-to-noise of
      an SPSC system at illumination levels that incur only at 1/15th of the rate of
      the photobleaching of the SPSC system. Although some of the relative efficiency
      of the CSU10 system may be attributed to the use of a CCD rather than a
      photomultiplier detector system, our analyses indicate that high-speed imaging
      with the SPSC system is limited by fluorescence saturation at the high levels of
      illumination frequently needed to collect images at high frame rates. The high
      speed, high efficiency and freedom from fluorescence saturation combine to make
      the CSU10 effective for extended imaging of living cells at rates capable of
      capturing the three-dimensional motion of endosomes moving up to several
      micrometres per second.

PMID- 15857377
TI  - Bootstrap methods for statistical inference from stereological estimates of
      volume fraction.
AB  - We suggest the use of bootstrap methods for inference from stereological
      estimates of volume fraction. An informal introduction to stereological
      estimation of volume fraction and to principles of bootstrap techniques is given.
      The bootstrap method is a robust computer-intensive resampling technique, based
      on independent random sampling from a data set with replacement. Bootstrap
      methods were used to estimate confidence intervals for volume fractions, and to
      test for a significant difference between estimated volume fractions from two
      samples. Two sampling designs are considered: independent replicated samples
      (visual fields) from a single object, and estimates of volume fraction from
      multiple independent objects. The methods are presented as worked examples on
      real data sets obtained from tumour pathology (mammary cancer, pancreatic
      cancer). The volume fraction of glandular lumina per total volume of the
      epithelial phase was chosen as target parameter. It indicates the degree of
      glandular differentiation in adenocarcinomas and is estimated as a ratio-of-means
      statistic with variable denominator within cases. The confidence intervals of the
      volume fraction estimated by the bootstrap method were slightly narrower than the
      parametrically calculated confidence intervals for all data sets. The outcomes of
      significance tests based on the bootstrap technique were unchanged as compared
      with classical tests based on the assumptions of normality and homoscedasticity
      of the data. Special attention was paid to the reproducibility of the bootstrap
      technique in replicated trials on the same data.

PMID- 15857378
TI  - Stereological measures of trabecular bone structure: comparison of 3D micro
      computed tomography with 2D histological sections in human proximal tibial bone
      biopsies.
AB  - Stereology applied on histological sections is the 'gold standard' for obtaining
      quantitative information on cancellous bone structure. Recent advances in micro
      computed tomography (microCT) have made it possible to acquire three-dimensional
      (3D) data non-destructively. However, before the 3D methods can be used as a
      substitute for the current 'gold standard' they have to be verified against the
      existing standard. The aim of this study was to compare bone structural measures
      obtained from 3D microCT data sets with those obtained by stereology performed on
      conventional histological sections using human tibial bone biopsies. Furthermore,
      this study forms the first step in introducing the proximal tibia as a potential
      bone examination location by peripheral quantitative CT and CT. Twenty-nine
      trabecular bone biopsies were obtained from autopsy material at the medial side
      of the proximal tibial metaphysis. The biopsies were embedded in
      methylmetacrylate before microCT scanning in a Scanco microCT 40 scanner at a
      resolution of 20 x 20 x 20 microm3, and the 3D data sets were analysed with a
      computer program. After microCT scanning, 16 sections were cut from the central 2
      mm of each biopsy and analysed with a computerized method. Trabecular bone volume
      (BV/TV) and connectivity density (CD) were estimated in both modalities, whereas
      trabecular bone pattern factor (TBPf) was estimated on the histological sections
      only. Trabecular thickness (Tb.Th), number (Tb.N) and separation (Tb.Sp), and
      structure model index (SMI) were estimated with the microCT method only.
      Excellent correlations were found between the two techniques for BV/TV (r = 0.95)
      and CD (r = 0.95). Additionally, an excellent relationship (r = 0.95) was
      ascertained between TBPf and SMI. The study revealed high correlations between
      measures of bone structure obtained from conventional 2D sections and 3D microCT
      data. This indicates that 3D microCT data sets can be used as a substitute for
      conventional histological sections for bone structural evaluations.

PMID- 15857379
TI  - About the role of boundary conditions on compositional imaging with a scanning
      electron microscope.
AB  - We consider the effects of different boundaries on the visibility of a specimen
      detail providing a compositional contrast in scanning electron microscopy,
      operating with backscattered electrons or secondary electrons. An object
      characterized by a gradual variation in composition, an As-doped region in Si, is
      investigated. The different boundaries in the cross-sectioned specimen correspond
      to the absence or presence of a poly-Si layer on top of the implanted region,
      deposited after the annealing treatment. It is shown that the interpretation
      model used for image formation is of paramount relevance for understanding the
      experimental results, indicating that the boundaries of the doped region are
      important in hindering or enhancing its visibility. The relevance of experimental
      parameters such as electron energy and probe dimension is also reported.

PMID- 15857380
TI  - An X-ray microscopy perspective on the effect of glutaraldehyde fixation on
      cells.
AB  - X-ray microscopy (XRM) is the only microscopy technique that can provide high
      resolution (30 nm) imaging of biological specimens without the need to fix, stain
      or section them. We aim to determine the effect, if any, of glutaraldehyde
      fixation on algae cells from the XRM perspective and thus provide beneficial
      information for both X-ray and electron microscopists on artefacts induced by
      glutaraldehyde fixation. Three species of microalgae, Microcystis aeruginosa,
      Anabaena spiroides and Chlorella vulgaris, were used in this study. XRM images
      were obtained from unfixed and glutaraldehyde-fixed cells and cell diameter and
      percentage X-ray absorbency were measured. The mean diameter of cells from fixed
      preparations was smaller than from unfixed preparations; the mean diameter of M.
      aeruginosa cells was significantly reduced from 3.92 microm in unfixed cells to
      3.43 microm in fixed cells (P < 0.05); in C. vulgaris the diameter of cells was
      also significantly reduced from 3.50 microm in unfixed to 2.98 microm in fixed
      samples (P < 0.05); whereas there was no significant reduction in the diameter of
      A. spiroides cells (4.04-3.90 microm). The protein crosslinking mechanism of
      glutaraldehyde probably generated free water molecules, which play an important
      role in radiation damage induced by X-rays. This was seen as mass loss and cell
      shrinkage, which in the present study occurred more frequently in fixed cells
      than in unfixed cells. In addition, we demonstrated that the uptake of
      glutaraldehyde by cells makes all protein constituents in the cell organize into
      a closely packed configuration, thus causing a rise in the percentage of X-ray
      absorbency. In fixed cells, this rise was approximately by a factor of two
      compared with unfixed samples in which protein constituents inside the cell are
      arranged in their native form.

PMID- 15857381
TI  - Estimation of the standard deviation in three-dimensional microscopy by spatial
      statistics.
AB  - Usually, the calibration process for three-dimensional microscopy involves the
      use of a reference flat surface. The random fluctuations of the topographic image
      for this reference surface are used for determining the uncertainty of the
      microscope. When the sample material or the measuring conditions of the
      microscope are modified (such as the objective used in a confocal microscope, or
      the tip in an atomic force microscope), the measuring conditions vary and thus a
      new calibration is required. In this work, a technique based on spatial
      statistics methods (more specifically, the variogram function) is proposed to
      determine accurately the standard deviation for three-dimensional microscopy that
      does not require a reference flat surface and therefore eliminates the need for a
      previous calibration process of this parameter.

PMID- 15857382
TI  - Presenilin function and gamma-secretase activity.
AB  - Alzheimer's disease (AD) is the most common form of dementia and is characterized
      pathologically by the accumulation of beta-amyloid (Abeta) plaques and
      neurofibrillary tangles in the brain. Genetic studies of AD first highlighted the
      importance of the presenilins (PS). Subsequent functional studies have
      demonstrated that PS form the catalytic subunit of the gamma-secretase complex
      that produces the Abeta peptide, confirming the central role of PS in AD biology.
      Here, we review the studies that have characterized PS function in the gamma
      secretase complex in Caenorhabditis elegans, mice and in in vitro cell culture
      systems, including studies of PS structure, PS interactions with substrates and
      other gamma-secretase complex members, and the evidence supporting the hypothesis
      that PS are aspartyl proteases that are active in intramembranous proteolysis. A
      thorough knowledge of the mechanism of PS cleavage in the context of the gamma
      secretase complex will further our understanding of the molecular mechanisms that
      cause AD, and may allow the development of therapeutics that can alter Abeta
      production and modify the risk for AD.

PMID- 15857383
TI  - Prion protein glycosylation.
AB  - The transmissible spongiform encephalopathies (TSE), or prion diseases are a
      group of transmissible neurodegenerative disorders of humans and animals.
      Although the infectious agent (the 'prion') has not yet been formally defined at
      the molecular level, much evidence exists to suggest that the major or sole
      component is an abnormal isoform of the host encoded prion protein (PrP).
      Different strains or isolates of the infectious agent exist, which exhibit
      characteristic disease phenotypes when transmitted to susceptible animals. In the
      absence of a nucleic acid genome it has been hard to accommodate the existence of
      TSE strains within the protein-only model of prion replication. Recent work
      examining the conformation and glycosylation patterns of disease-associated PrP
      has shown that these post-translational modifications show strain-specific
      properties and contribute to the molecular basis of TSE strain variation. This
      article will review the role of glycosylation in the susceptibility of cellular
      PrP to conversion to the disease-associated conformation and the role of
      glycosylation as a marker of TSE strain type.

PMID- 15857384
TI  - In vivo up-regulation of brain-derived neurotrophic factor in specific brain
      areas by chronic exposure to Delta-tetrahydrocannabinol.
AB  - Cannabinoids are widely abused drugs. Here we show that chronic administration of
      Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the active psychotropic agent in
      marijuana and hashish, at 1.5 mg per kg per day intraperitoneally for 7 days,
      increases the expression, at both mRNA and protein levels, of brain-derived
      neurotrophic factor (BDNF), in specific rat brain areas, notably in those
      involved in reward and addiction. Real-time PCR revealed a 10-fold up-regulation
      of BDNF mRNA in the nucleus accumbens (NAc) upon chronic Delta(9)-THC treatment,
      but there was no change at 3 or 24 h after a single injection. Smaller increases
      in mRNA levels were found in the ventral tegmental area (VTA), medial prefrontal
      cortex and paraventricular nucleus (PVN). Immunohistochemistry showed large
      increases in BDNF-stained cells in the NAc (5.5-fold), posterior VTA (4-fold) and
      PVN (1.7-fold), but no change was observed in the anterior VTA, hippocampus or
      dorsal striatum. Altogether, our study indicates that chronic exposure to
      Delta(9)-THC up-regulates BDNF in specific brain areas involved with reward, and
      provides evidence for different BDNF expression in the anterior and posterior
      VTA. Moreover, BDNF is known to modulate synaptic plasticity and adaptive
      processes underlying learning and memory, leading to long-term functional and
      structural modification of synaptic connections. We suggest that Delta(9)-THC up
      regulation of BDNF expression has an important role in inducing the neuroadaptive
      processes taking place upon exposure to cannabinoids.

PMID- 15857385
TI  - Kinetics and subunit composition of NMDA receptors in respiratory-related
      neurons.
AB  - NMDA receptors are involved in a variety of brainstem functions. The excitatory
      postsynaptic NMDA currents of pre-Botzinger complex interneurons and hypoglossal
      motoneurons, which are located in the medulla oblongata, show remarkably fast
      deactivation kinetics of approximately 30 ms compared with NMDA receptors in
      other types of neurons. Because structural heterogeneity might be the basis for
      physiological properties, we examined the expression of six NMDA receptor
      subunits (NMDAR1, NR2A-2D, and NR3A) plus eight NMDR1 splice variants in pre
      Botzinger complex, hypoglossal and, for comparison, neurons from the nucleus of
      the solitary tract in young rats using single cell multiplex RT-PCR. Expression
      of NR2A, NR2B, and NR2D was observed in all three cell types while NR3A was much
      more abundant in pre-Botzinger complex interneurons, which belong to the rhythm
      generator of respiratory activity. In hypoglossal neurons, the NMDAR1 splice
      variants NMDAR1-4a and NMDAR1-4b were found. In neurons of the nucleus of the
      solitary tract, instead of NMDAR1-4b, the NMDAR1-2a splice variant was detected.
      This differential expression of modulatory splice variants might be the molecular
      basis for the characteristic functional properties of NMDA receptors, as neurons
      expressing a special NMDAR1 splice variant at the mRNA level show fast kinetics
      compared with neurons lacking this splice variant.

PMID- 15857386
TI  - Induction of aquaporin 1 but not aquaporin 4 messenger RNA in rat primary brain
      microvessel endothelial cells in culture.
AB  - Aquaporins (AQPs) are a family of proteins that mediate water transport across
      cells, but the extent to which they are involved in water transport across
      endothelial cells of the blood-brain barrier is not clear. Expression of AQP1 and
      AQP4 in rat brain microvessel endothelial cells was investigated in order to
      determine whether these isoforms were present and, in particular, to examine the
      hypothesis that brain endothelial expression of AQPs is dynamic and regulated by
      astrocytic influences. Reverse-transcriptase-polymerase chain reaction (RT-PCR)
      and immunocytochemistry showed that AQP1 mRNA and protein are present at very low
      levels in primary rat brain microvessel endothelial cells, and are up-regulated
      in passaged cells. Upon passage, endothelial cell expression of mdr1a mRNA is
      decreased, indicating loss of blood-brain barrier phenotype. In passage 4
      endothelial cells, AQP1 mRNA levels are reduced by coculture above rat
      astrocytes, demonstrating that astrocytic influences are important in maintaining
      the low levels of AQP1 characteristic of the blood-brain barrier endothelium.
      Reverse-transcriptase-PCR revealed very low levels of AQP1 mRNA present in the
      RBE4 rat brain microvessel endothelial cell line, with no expression detected in
      primary cultures of rat astrocytes or in the C6 rat glioma cell line. In
      contrast, AQP4 mRNA is strongly expressed in astrocytes, but no expression is
      found in primary or passaged brain microvessel endothelial cells, or in RBE4 or
      C6 cells. Our results support the concept that expression of AQP1, which is seen
      in many non-brain endothelia, is suppressed in the specialized endothelium of the
      blood-brain barrier.

PMID- 15857387
TI  - Integrin signaling cascades are operational in adult hippocampal synapses and
      modulate NMDA receptor physiology.
AB  - Integrin class adhesion proteins are concentrated at adult brain synapses.
      Whether synaptic integrins engage kinase signaling cascades has not been
      determined, but is a question of importance to ideas about integrin involvement
      in functional synaptic plasticity. Accordingly, synaptoneurosomes from adult rat
      brain were used to test if matrix ligands activate integrin-associated tyrosine
      kinases, and if integrin signaling targets include NMDA-class glutamate
      neurotransmitter receptors. The integrin ligand peptide Gly-Arg-Gly-Asp-Ser-Pro
      (GRGDSP) induced rapid (within 5 min) and robust increases in tyrosine
      phosphorylation of focal adhesion kinase, proline-rich tyrosine kinase 2 and Src
      family kinases. Increases were similarly induced by the native ligand
      fibronectin, blocked with neutralizing antibodies to beta1 integrin, and not
      obtained with control peptides, indicating that kinase activation was integrin
      mediated. Both GRGDSP and fibronectin caused rapid Src kinase-dependent increases
      in tyrosine phosphorylation of NMDA receptor subunits NR2A and NR2B in
      synaptoneurosomes and acute hippocampal slices. Tests of the physiological
      significance of the latter result showed that ligand treatment caused a rapid and
      beta1 integrin-dependent increase in NMDA receptor-mediated synaptic responses.
      These results provide the first evidence that, in adult brain, synaptic integrins
      activate local kinase cascades with potent effects on the operation of nearby
      neurotransmitter receptors implicated in synaptic plasticity.

PMID- 15857389
TI  - Mutations in the neurofilament light gene linked to Charcot-Marie-Tooth disease
      cause defects in transport.
AB  - Neurofilament light gene mutations have been linked to a subset of patients with
      Charcot-Marie-Tooth disease, the most common inherited motor and sensory
      neuropathy. We have previously shown that Charcot-Marie-Tooth-linked mutant
      neurofilament light assembles abnormally in non-neuronal cells. In this study, we
      have characterized the effects of expression of mutant neurofilament light
      proteins on axonal transport in a neuronal cell culture model. We demonstrated
      that the Charcot-Marie-Tooth-linked neurofilament light mutations: (i) affect the
      axonal transport of mutant neurofilaments; (ii) have a dominant-negative effect
      on the transport of wild-type neurofilaments; (iii) affect the transport of
      mitochondria and the anterograde axonal transport marker human amyloid precursor
      protein; (iv) result in alterations of retrograde axonal transport and (v) cause
      fragmentation of the Golgi apparatus. Increased neuritic degeneration was
      observed in neuronal cells overexpressing neurofilament light mutants. Our
      results suggest that these generalized axonal transport defects could be
      responsible for the neuropathy in Charcot-Marie-Tooth disease.

PMID- 15857388
TI  - Regulation of mitochondrial gene expression by energy demand in neural cells.
AB  - Mitochondrial DNA (mtDNA) encodes critical subunit proteins of the oxidative
      phosphorylation (OXPHOS) complex that generates ATP. This study tested the
      hypothesis that mitochondrial gene expression in neural cells is regulated by
      energy demand, as modified via stimulation of cellular sodium transport. Exposure
      of PC12S cells to the sodium ionophore monensin (250 nm) for 1-6 h caused a 13
      60% decrease in cellular ATP (from 15 to 5 nmol per mg protein at 6 h). Levels of
      mitochondrial DNA-encoded mRNAs (mt-mRNAs) increased significantly (150%) within
      the first hour of exposure to monensin, and then decreased significantly (50%) at
      3-4 h. Levels of mtDNA-encoded 12S rRNA and nuclear DNA-encoded OXPHOS subunit
      mRNAs were not significantly affected. Exposure of primary cerebellar neuronal
      cultures to the excitatory amino acid glutamate caused a similar rapid and
      significant increase followed by a significant decrease in cell mt-mRNA levels.
      The monensin-induced initial increase in mt-mRNA levels was abolished by
      pretreatment with actinomycin D or by reducing extracellular sodium ion
      concentration. The monensin-induced delayed reduction in mt-mRNA levels was
      accelerated in the presence of actinomycin D, and was accompanied by a 67%
      reduction in the half-life (from 3.6 to 1.2 h). Exposure of PC12S cells to 2
      deoxy-d-glucose significantly decreased cellular ATP levels (from 14.2 to 7.1
      nmol per mg protein at 8 h), and increased mt-mRNA levels. These results suggest
      a physiological transcriptional mechanism of regulation of mitochondrial gene
      expression by energy demand and a post-transcriptional regulation that is
      independent of energy status of the cell.

PMID- 15857390
TI  - Elevation of the Hsp70 chaperone does not effect toxicity in mouse models of
      familial amyotrophic lateral sclerosis.
AB  - Mutations in copper/zinc superoxide dismutase (SOD1) account for 10-20% of a
      familial form of amyotrophic lateral sclerosis (ALS). A common feature of SOD1
      mutants is abnormal aggregation of the aberrant SOD1 in neurons and glia. We now
      report that in ALS transgenic mouse models the constitutively expressed heat
      shock protein 70 (Hsp70) is mislocalized into aggregates together with mutant
      SOD1 and ubiquitin. Forcing increased synthesis of Hsp70 ameliorates both
      aggregate formation and toxicity in primary motor neurons in culture. However,
      chronic increase in an inducible form of Hsp70 to about 10-fold its normal level
      is shown here not to affect disease course or pathology developed in mice from
      accumulation of any of three familial ALS causing SOD1 mutants with different
      underlying biochemical characteristics. Therefore, increasing Hsp70 to a level
      that is protective in mouse models of acute ischemic insult and selected
      neurodegenerative disorders is not sufficient to ameliorate mutant SOD1-mediated
      toxicity.

PMID- 15857391
TI  - Involvement of gamma protein kinase C in estrogen-induced neuroprotection against
      focal brain ischemia through G protein-coupled estrogen receptor.
AB  - The neuroprotective effects of estrogen were studied in the ischemic model mice
      by 90 min transient unilateral middle cerebral artery occlusion (MCAO) followed
      by 22.5 h reperfusion. The total infarct size in C57BL/6 female mice after MCAO
      and reperfusion was significantly smaller than that in male mice. Intraperitoneal
      injection of estrogen after the start of reperfusion significantly reduced the
      infarct volume in the male mice. However, no significant gender difference was
      found in total infarct size in gamma protein kinase C (PKC)-knockout mice,
      suggesting that the neuroprotective effects of estrogen are due to the activation
      of a specific subtype of PKC, gammaPKC, a neuron-specific PKC subtype, in the
      brain. We demonstrated that exogenous estrogen-induced neuroprotection was
      attenuated in gammaPKC-knockout mice. Immunocytochemical study showed that
      gammaPKC was translocated to nerve fiber-like structures when observed shortly
      after MCAO and reperfusion. We also visualized the rapid and reversible
      translocation of gammaPKC-GFP (green fluorescent protein) by estrogen stimulation
      in living CHO-K1 cells. These results suggest that the activation of gammaPKC
      through the G-protein-coupled estrogen receptors on the plasma membrane is
      involved in the estrogen-induced neuroprotection against focal brain ischemia.

PMID- 15857392
TI  - Src homology domains in phospholipase C-gamma1 mediate its anti-apoptotic action
      through regulating the enzymatic activity.
AB  - Phospholipase-gamma1 (PLC-gamma1) prevents programmed cell death, for which the
      enzymatic activity has been implicated. However, the biological function of Src
      homology (SH) domains of PLC-gamma1 in promoting cell survival remains elusive.
      Here, we showed that deletion of the N-SH2 domain or both N-SH2 and C-SH2
      domains, but not the SH3 domain, abolished the anti-apoptotic activity of PLC
      gamma1. Surprisingly, removal of the whole SH domain inhibited apoptosis. The
      lipase-inactive PLC-gamma1 mutant (LIM) failed to suppress apoptosis. Moreover,
      the phospholipase activity in SH3- or whole SH domain-deleted cells was
      comparable to that of wild-type cells. By contrast, the enzymatic activity was
      substantially ablated in SH2 domain-deleted or LIM cells. A pharmacological
      inhibitor of PLC-gamma1 robustly diminished the anti-apoptotic action in wild
      type, SH3- or whole SH domain-deleted cells, whereas pretreatment of SH2 domain
      deleted or LIM cells with agents activating PKC and calcium mobilization markedly
      promoted cell survival. These results indicate that SH domains in PLC-gamma1
      might mediate its anti-apoptotic action by regulating the enzymatic activity.

PMID- 15857393
TI  - Dopamine D2 receptor stimulation of mitogen-activated protein kinases mediated by
      cell type-dependent transactivation of receptor tyrosine kinases.
AB  - Dopamine D2 receptor activation of extracellular signal-regulated kinases (ERKs)
      in non-neuronal human embryonic kidney 293 cells was dependent on transactivation
      of the platelet-derived growth factor (PDGF) receptor, as demonstrated by the
      effect of the PDGF receptor inhibitors tyrphostin A9 and AG 370 on quinpirole
      induced phosphorylation of ERKs and by quinpirole-induced tyrosine
      phosphorylation of the PDGF receptor. In contrast, ectopically expressed D2
      receptor or endogenous D2-like receptor activation of ERKs in NS20Y neuroblastoma
      cells, which express little or no PDGF receptor, or in rat neostriatal neurons
      was largely dependent on transactivation of the epidermal growth factor (EGF)
      receptor, as demonstrated using the EGF receptor inhibitor AG 1478 and by
      quinpirole-induced phosphorylation of the EGF receptor. The D2 receptor agonist
      quinpirole enhanced the coprecipitation of D2 and EGF receptors in NS20Y cells,
      suggesting that D2 receptor activation induced the formation of a macromolecular
      signaling complex that includes both receptors. Transactivation of the EGF
      receptor also involved the activity of a matrix metalloproteinase. Thus, although
      D2 receptor stimulation of ERKs in both cell lines was decreased by inhibitors of
      ERK kinase, Src-family protein tyrosine kinases, and serine/threonine protein
      kinases, D2-like receptors activated ERKs via transactivation of the EGF receptor
      in NS20Y neuroblastoma cells and rat embryonic neostriatal neurons, but via
      transactivation of the PDGF receptor in 293 cells.

PMID- 15857394
TI  - 5-HT receptors couple to activation of Akt, but not extracellular-regulated
      kinase (ERK), in cultured hippocampal neurons.
AB  - 5-HT(1A) receptors have been hypothesized to mediate some of the neuronal
      plasticity and behavioral responses stimulated by serotonin selective reuptake
      inhibitors. Although the cellular signaling pathways required for inducing these
      actions have not yet been determined, roles for the neuroprotective extracellular
      regulated kinase (ERK) mitogen-activated protein (MAP) kinase and Akt pathways
      have been suggested. In the current studies we have utilized primary cultures to
      directly determine whether hippocampal 5-HT(1A) receptors couple to activation of
      Akt and ERK. We found that E18 hippocampal neurons exhibit a twofold activation
      of Akt when exposed to nanomolar concentrations of 5-HT. The 5-HT(1/7) receptor
      selective agonist 5-carboxamidotryptamine maleate (5-CT) and the 5-HT(1A/7)
      receptor-selective agonist 8-hydroxy-N,N-dipropyl-aminotetralin (8-OH-DPAT)
      maleate were found to activate Akt with equal efficacy, and similar potency, to 5
      HT. p-MPPI and WAY-100635, antagonists selective for 5-HT(1A) receptors,
      completely inhibited 5-CT- stimulated Akt activation. Activation of Akt was also
      inhibited by pretreatment with pertussis toxin as well as the
      phosphatidylinositol 3-kinase inhibitors, wortmannin and LY294002. In contrast,
      the 5-HT selective antagonist, SB269970, caused no inhibition. Although the
      density of 5-HT(1A) receptors expressed by cultured neurons was sufficient to
      activate Akt, no activation of ERK was observed. These findings suggest that Akt,
      and not ERK, may be relevant to previous reports of hippocampal 5-HT(1A)
      receptors mediating neurotrophic responses.

PMID- 15857395
TI  - STAT5A interacts with and is phosphorylated upon activation of the mu-opioid
      receptor.
AB  - Signal Transducers and Activators of Transcription (STATs) are transcription
      factors shown to be activated by G protein-coupled receptors. In the present
      study, we demonstrate that acute morphine or [D-Ala(2),N-Me-Phe(4),Gly(5)
      ol]enkephalin (DAMGO) exposure of COS-7 cells transiently transfected with the
      micro-opioid receptor and STAT5A, leads to receptor-dependent tyrosine
      phosphorylation of STAT5A. Activation of HEK293 cells, stably expressing the
      micro-opioid receptor with micro-opioid agonists results in the transcriptional
      activation of a STAT-responsive reporter gene. Pertussis toxin has no effect on
      the level of STAT5A phosphorylation, while the Src inhibitor PP1 abolishes opioid
      dependent STAT5A phosphorylation. All three opioid receptor subtypes -micro,
      delta and kappa- share the conserved motif YXXL (amino-acids 336-339 for the
      micro-opioid receptor), known to be critical for STAT5A/5B binding. Co
      immunoprecipitation and pull-down experiments using a GST-carboxyl-terminal tail
      of the micro-opioid receptor and rat brain, or COS-7 cell cytosolic extracts,
      demonstrate the direct binding of STAT5A to this region. Mutation of the Y336 to
      alanine does not prevent STAT5A binding, whereas deletion of the entire putative
      STAT5A binding site YXXL abolishes STAT5A interaction to the carboxyl-terminal
      tail of the micro-opioid receptor. Collectively, our results demonstrate the
      association of STAT5A with the micro-opioid receptor and reveal novel signalling
      pathways in the regulation of transcription by the micro-opioid receptor.

PMID- 15857396
TI  - Modulatory effects of progesterone on inducible nitric oxide synthase expression
      in vivo and in vitro.
AB  - Nitric oxide (NO) is produced in the CNS following injury-induced expression of
      inducible nitric oxide synthase (iNOS), yet its role as protective or damaging is
      unclear. Previous studies investigating the therapeutic potential of female sex
      steroids in stroke and trauma suggest that NO from this source is harmful, since
      oestradiol and progesterone decreased the level of iNOS expression in vitro and
      improved neurological outcome. We investigated the effects of progesterone on
      stroke-induced expression of iNOS in mice, as well as cytokine-induced expression
      of iNOS and its transcriptional activators in cells relevant to injury. We
      observed a significant reduction in stroke-induced iNOS transcript in
      progesterone-treated mice and in cultured macrophages. In contrast, progesterone
      significantly amplifed cytokine-induced iNOS mRNA in cultured primary astrocytes,
      although the expression of protein was decreased. We sequenced upstream of the
      1.5 kb reported iNOS promoter region and identified a potential progesterone
      response element (PRE). Astrocytes transiently transfected with iNOS promoter/CAT
      reporter gene constructs containing the PRE displayed a significant increase in
      induction of CAT expression after progesterone treatment, and this was diminished
      in cells transfected with a construct containing a disrupted PRE. These
      observations suggest the involvement of iNOS in the neuroprotective effects of
      progesterone.

PMID- 15857397
TI  - Real-time quantitative PCR analysis of temporal-spatial alterations in gene
      expression after spinal cord contusion.
AB  - Rat spinal cord contusion injury models the histopathology associated with much
      clinical spinal cord injury (SCI). Studies on altered gene expression after SCI
      in these models may identify therapeutic targets for reducing secondary injury
      after the initial trauma and/or enhancing recovery processes. However, complex
      spatial and temporal alterations after injury could complicate interpretation of
      changes in gene expression. To test this hypothesis, we selected six genes and
      studied their temporal and spatial patterns of expression at 1 h, 1, 3 and 7 days
      after a standardized spinal cord contusion produced by a weight drop device (10 g
      x 25 mm at T8). Real-time RT-PCR using TaqMan probes was employed to quantify
      mRNA for proteolipid protein, glyceraldehyde-3-phosphate dehydrogenase, glial
      fibrillary acidic protein, nestin, and the GluR2 and NR1 subunits of glutamate
      receptors. We found widely different temporal and spatial patterns of altered
      gene expression after SCI, including instances of opposing up- and down
      regulation at different locations in tissue immediately adjacent to the injury
      site. We conclude that greater use of the reliable and extremely sensitive
      technique of quantitative real-time PCR for regional tissue analysis is important
      for understanding the altered gene expression that occurs after CNS trauma.

PMID- 15857398
TI  - Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer's
      disease.
AB  - Increasing evidence suggests that oxidative stress is associated with normal
      aging and several neurodegenerative diseases, including Alzheimer's disease (AD).
      Here we quantified multiple oxidized bases in nuclear and mitochondrial DNA of
      frontal, parietal, and temporal lobes and cerebellum from short postmortem
      interval AD brain and age-matched control subjects using gas chromatography/mass
      spectrometry with selective ion monitoring (GC/MS-SIM) and stable labeled
      internal standards. Nuclear and mitochondrial DNA were extracted from eight AD
      and eight age-matched control subjects. We found that levels of multiple oxidized
      bases in AD brain specimens were significantly (p < 0.05) higher in frontal,
      parietal, and temporal lobes compared to control subjects and that mitochondrial
      DNA had approximately 10-fold higher levels of oxidized bases than nuclear DNA.
      These data are consistent with higher levels of oxidative stress in mitochondria.
      Eight-hydroxyguanine, a widely studied biomarker of DNA damage, was approximately
      10-fold higher than other oxidized base adducts in both AD and control subjects.
      DNA from temporal lobe showed the most oxidative damage, whereas cerebellum was
      only slightly affected in AD brains. These results suggest that oxidative damage
      to mitochondrial DNA may contribute to the neurodegeneration of AD.

PMID- 15857399
TI  - Stromal cell-derived factor-1alpha directly modulates voltage-dependent currents
      of the action potential in mammalian neuronal cells.
AB  - Stromal cell-derived factor-1alpha (SDF-1alpha) is a chemokine whose receptor,
      CXCR4, is distributed in specific brain areas including hypothalamus. SDF-1alpha
      has recently been found to play important roles in neurons, although direct
      modulation of voltage-gated ionic channels has never been shown. In order to
      clarify this issue, we performed patch-clamp experiments in fetal mouse
      hypothalamic neurons in culture. SDF-1alpha (10 nm) decreased the peak and rising
      slope of the action potentials and spike discharge frequency in 22% of
      hypothalamic neurons tested. This effect was blocked by the CXCR4 antagonist AMD
      3100 (1 microm) but not by the metabotropic glutamate receptor antagonist MCPG
      (500 microm), indicating a direct action of SDF-1alpha on its cognate receptor.
      This effect involved a depression of both inward and outward voltage-dependent
      currents of the action potential. We confirmed these effects in the human
      neuroblastoma cell line SH-SY5Y, which endogenously expresses CXCR4. Voltage
      clamp experiments revealed that SDF-1alpha induced a 20% decrease in the peak of
      the tetrodotoxin-sensitive sodium current and tetraethylammonium-sensitive
      delayed rectifier potassium current, respectively. Both effects were
      concentration dependent, and blocked by AMD 3100 (200 nm). This dual effect was
      reduced or blocked by 0.4 mm GTPgammaS G-protein pre-activation or by pre
      treatment with the G-protein inhibitor pertussis toxin (200 ng/mL), suggesting
      that it is mediated via activation of a G(i/o) protein. This study extends the
      functions of SDF-1alpha to a direct modulation of voltage-dependent membrane
      currents of neuronal cells.

PMID- 15857400
TI  - Influences of dopaminergic lesion on epidermal growth factor-ErbB signals in
      Parkinson's disease and its model: neurotrophic implication in nigrostriatal
      neurons.
AB  - Epidermal growth factor (EGF) is a member of a structurally related family
      containing heparin-binding EGF-like growth factor (HB-EGF) and transforming
      growth factor alpha (TGFalpha) that exerts neurotrophic activity on midbrain
      dopaminergic neurons. To examine neurotrophic abnormality in Parkinson's disease
      (PD), we measured the protein content of EGF, TGFalpha, and HB-EGF in post-mortem
      brains of patients with Parkinson's disease and age-matched control subjects.
      Protein levels of EGF and tyrosine hydroxylase were decreased in the prefrontal
      cortex and the striatum of patients. In contrast, HB-EGF and TGFalpha levels were
      not significantly altered in either region. The expression of EGF receptors
      (ErbB1 and ErbB2, but not ErbB3 or ErbB4) was down-regulated significantly in the
      same forebrain regions. The same phenomenon was mimicked in rats by dopaminergic
      lesions induced by nigral 6-hydroxydopamine infusion. EGF and ErbB1 levels in the
      striatum of the PD model were markedly reduced on the lesioned side, compared
      with the control hemisphere. Subchronic supplement of EGF in the striatum of the
      PD model locally prevented the dopaminergic neurodegeration as measured by
      tyrosine hydroxylase immunoreactivity. These findings suggest that the
      neurotrophic activity of EGF is maintained by afferent signals of midbrain
      dopaminergic neurons and is impaired in patients with Parkinson's disease.

PMID- 15857401
TI  - Ras/ERK signalling in cannabinoid tolerance: from behaviour to cellular aspects.
AB  - We investigated the role of the Ras/extracellular-regulated kinase (ERK) pathway
      in the development of tolerance to Delta(9)-tetrahydrocannabinol (THC)-induced
      reduction in spontaneous locomotor activity by a genetic (Ras-specific guanine
      nucleotide exchange factor (Ras-GRF1) knock-out mice) and pharmacological
      approach. Pre-treatment of wild-type mice with SL327 (50 mg/kg i.p.), a specific
      inhibitor of mitogen-activated protein kinase kinase (MEK), the upstream kinase
      of ERK, fully prevented the development of tolerance to THC-induced
      hypolocomotion. We investigated the impact of the inhibition of ERK activation on
      the biological processes involved in cannabinoid tolerance (receptor down
      regulation and desensitization), by autoradiographic cannabinoid CB1 receptor and
      cannabinoid-stimulated [(35)S]GTPgammaS binding studies in subchronically treated
      mice (THC, 10 mg/kg s.c., twice a day for 5 days). In the caudate putamen and
      cerebellum of Ras-GRF1 knock-out mice and SL327 pre-treated wild-type mice, CB1
      receptor down-regulation and desensitization did not occur, suggesting that ERK
      activation might account for CB1 receptor plasticity involved in the development
      of tolerance to THC hypolocomotor effect. In contrast, the hippocampus and
      prefrontal cortex showed CB1 receptor adaptations regardless of the genetic or
      pharmacological inhibition of the ERK pathway, suggesting regional variability in
      the cellular events underlying the altered CB1 receptor function. These findings
      suggest that at least in the caudate putamen and cerebellum, the Ras/ERK pathway
      is essential for triggering the alteration in CB1 receptor function responsible
      for tolerance to THC-induced hypomotility.

PMID- 15857403
TI  - Misregulation of poly(ADP-ribose) polymerase-1 activity and cell type-specific
      loss of poly(ADP-ribose) synthesis in the cerebellum of aged rats.
AB  - Protein modification by ADP-ribose polymers is a common regulatory mechanism in
      eukaryotic cells and is involved in several aspects of brain physiology and
      physiopathology, including neurotransmission, memory formation, neurotoxicity,
      ageing and age-associated diseases. Here we show age-related misregulation of
      poly(ADP-ribose) synthesis in rat cerebellum as revealed by: (i) reduced poly(ADP
      ribose) polymerase-1 (PARP-1) activation in response to enzymatic DNA cleavage,
      (ii) altered protein poly(ADP-ribosyl)ation profiles in isolated nuclei, and
      (iii) cell type-specific loss of poly(ADP-ribosyl)ation capacity in granule cell
      layer and Purkinje cells in vivo. In particular, although PARP-1 could be
      detected in virtually all granule cells, only a fraction of them appeared to be
      actively engaged in poly(ADP-ribose) synthesis and this fraction was reduced in
      old rat cerebellum. NAD(+), quantified in tissue homogenates, was essentially the
      same in the cerebellum of young and old rats suggesting that in vivo factors
      other than PARP-1 content and/or NAD(+) levels may be responsible for the age
      associated lowering of poly(ADP-ribose) synthesis. Moreover, PARP-1 expression
      was substantially down-regulated in Purkinje cells of senescent rats.

PMID- 15857402
TI  - Suberoylanilide hydroxamic acid (SAHA) has potent anti-glioma properties in
      vitro, ex vivo and in vivo.
AB  - Current treatment modalities for malignant gliomas do not allow long-term
      survival. Here, we identify suberoylanilide hydroxamic acid (SAHA), an inhibitor
      of histone deacetylases (HDAC), as an effective experimental anti-glioma agent.
      Administration of SAHA to various glioma cell lines obtained from human, rat and
      mouse inhibited tumour cell growth in a range of 1-10 microm. This anti-glioma
      property is associated with up-regulation of the cell cycle control protein
      p21/WAF, as well as the induction of apoptosis. A novel tumour invasion model
      using slice cultures of rat brain corroborated the anti-glioma properties of SAHA
      in the organotypic brain environment. In this model, glioma invasion compromised
      adjacent brain parenchyma, and this tumour-associated cytotoxicity could be
      inhibited by SAHA. In addition, a 10-fold dose escalation experiment did not
      challenge the viability of cultured brain slices. In vivo, a single intratumoural
      injection of SAHA 7 days after orthotopic implantation of glioma cells in
      syngeneic rats doubled their survival time. These observations identify chromatin
      modifying enzymes as possible and promising targets for the pharmacotherapy of
      malignant gliomas.

PMID- 15857404
TI  - Vaccination alone or in combination with pyridostigmine promotes and prolongs
      activation of stress-activated kinases induced by stress in the mouse brain.
AB  - Gulf war illnesses (GWI) are currently affecting thousands of veterans. To date,
      the molecular mechanisms underlying the pathogenesis of these illnesses remain
      unknown. During Gulf war I, military personnel were exposed to multiple
      stressors, one or more vaccines, pyridostigmine (PY), and other chemicals. In our
      previous studies, we found that stress induces activation of mitogen activated
      protein-kinase kinase 4 (MKK4) and c-Jun-N-terminal kinase (JNK) in the mouse
      brain (Liu et al. 2004). Our working hypothesis is that stress, vaccination, and
      PY may synergistically induce activation of MKK4 and JNK in the brain, leading to
      over-activation of these kinases and neurological injuries. To test our
      hypothesis, we examined the effect of keyhole limpet hemocyanin (KLH)
      immunization alone or in combination with PY on activation of MKK4 and JNK
      induced by stress. We found that KLH immunization alone had a small effect on
      MKK4 or JNK activity but it significantly enhanced and prolonged activation of
      these kinases induced by stress, from a few hours to several days. Additionally,
      KLH immunization caused activation of p38MAPK. PY treatment further enhanced and
      prolonged activation of these kinases induced by stress in combination with KLH
      immunization and triggered activation of caspase-3. Our current studies suggest
      that stress, vaccination, and PY may synergistically act on multiple stress
      activated kinases in the brain to cause neurological impairments in GWI.

PMID- 15857405
TI  - Neuroprotective effects of preconditioning ischaemia on ischaemic brain injury
      through inhibition of mixed-lineage kinase 3 via NMDA receptor-mediated Akt1
      activation.
AB  - A number of works show that the mitogen-activated protein kinase (MAPK)
      signalling pathway responds actively in cerebral ischaemia and reperfusion. We
      undertook our present studies to clarify the role of mixed-lineage kinase 3
      (MLK3), a MAPK kinase kinase (MAPKKK) in MAPK cascades, in global ischaemia and
      ischaemic tolerance. The mechanism concerning NMDA receptor-mediated Akt1
      activation underlying ischaemic tolerance, was also investigated. Sprague-Dawley
      rats were subjected to 6 min of ischaemia and differing times of reperfusion. Our
      results showed MLK3 was activated in the hippocampal CA1 region with two peaks
      occurring at 30 min and 6 h, respectively. This activation returned to base level
      3 days later. Both preconditioning with 3 min of sublethal ischaemia and NMDA
      pretreatment inhibited the 6-h peak of activation. However, pretreatment of
      ketamine before preconditioning reversed the inhibiting effect of preconditioning
      on MLK3 activation at 6 h of reperfusion. In the case of Akt1, however,
      preconditioning and NMDA pretreatment enhanced Akt1 activation at 10 min of
      reperfusion. Furthermore, ketamine pretreatment reversed preconditioning-induced
      increase of Akt1 activation. We also noted that pretreatment of LY294002 before
      preconditioning reversed both the inhibition of MLK3 activation at 6 h of
      reperfusion and the increase in Akt1 activation at 10 min of reperfusion. The
      above-mentioned results lead us to conclude that, in the hippocampal CA1 region,
      preconditioning inhibits MLK3 activation after lethal ischaemia and reperfusion
      and, furthermore, this effect is mediated by Akt1 activation through NMDA
      receptor stimulation.

PMID- 15857406
TI  - Role of oxidative stress in paraquat-induced dopaminergic cell degeneration.
AB  - Systemic treatment of mice with the herbicide paraquat causes the selective loss
      of nigrostriatal dopaminergic neurons, reproducing the primary neurodegenerative
      feature of Parkinson's disease. To elucidate the role of oxidative damage in
      paraquat neurotoxicity, the time-course of neurodegeneration was correlated to
      changes in 4-hydroxy-2-nonenal (4-HNE), a lipid peroxidation marker. When mice
      were exposed to three weekly injections of paraquat, no nigral dopaminergic cell
      loss was observed after the first administration, whereas a significant reduction
      of neurons followed the second exposure. Changes in the number of nigral 4-HNE
      positive neurons suggest a relationship between lipid peroxidation and neuronal
      death, since a dramatic increase in this number coincided with the onset and
      development of neurodegeneration after the second toxicant injection.
      Interestingly, the third paraquat administration did not cause any increase in 4
      HNE-immunoreactive cells, nor did it produce any additional dopaminergic cell
      loss. Further evidence of paraquat-induced oxidative injury derives from the
      observation of nitrotyrosine immunoreactivity in the substantia nigra of paraquat
      treated animals and from experiments with ferritin transgenic mice. These mice,
      which are characterized by a decreased susceptibility to oxidative stress, were
      completely resistant to the increase in 4-HNE-positive neurons and the cell death
      caused by paraquat. Thus, paraquat exposure yields a model that emphasizes the
      susceptibility of dopaminergic neurons to oxidative damage.

PMID- 15857407
TI  - Apolipoprotein J (clusterin) activates rodent microglia in vivo and in vitro.
AB  - Apolipoprotein J (apoJ; also known as clusterin and sulfated glycoprotein (SGP)
      2) is associated with senile plaques in degenerating regions of Alzheimer's
      disease brains, where activated microglia are also prominent. We show a
      functional link between apoJ and activated microglia by demonstrating that
      exogenous apoJ activates rodent microglia in vivo and in vitro.
      Intracerebroventricular infusion of purified human plasma apoJ ( approximately 4
      microg over 28 days) activated parenchymal microglia to a phenotype characterized
      by enlarged cell bodies and processes (phosphotyrosine immunostaining). In vitro,
      primary rat microglia were also activated by apoJ, with changes in morphology and
      induction of major histocompatibility complex class II (MHCII) antigen. ApoJ
      increased the secretion of reactive nitrogen intermediates in a dose-dependent
      manner (EC(50) 112 nm), which was completely blocked by aminoguanidine (AG), a
      nitric oxide synthase inhibitor. However, AG did not block the increased
      secretion of tumor necrosis factor-alpha by apoJ (EC(50) 55 nm). Microglial
      activation by apoJ was also blocked by an anti-apoJ monoclonal antibody (G7), and
      by chemical cleavage of apoJ with 2-nitro-5-thiocyanobenzoate. The mitogen
      activated protein kinase kinase and protein kinase C inhibitors PD98059 and H7
      inhibited apoJ-mediated induction of reactive nitrogen intermediate secretion
      from cultured microglia. As a functional measure, apoJ-activated microglia
      secreted neurotoxic agents in a microglia-neuron co-culture model. We hypothesize
      that ApoJ contributes to chronic inflammation and neurotoxicity through direct
      effects on microglia.

PMID- 15857408
TI  - Role of glutathione in intracellular amyloid-alpha precursor protein/carboxy
      terminal fragment aggregation and associated cytotoxicity.
AB  - Abstract Alterations in glutathione (GSH) metabolism are associated with
      neurodegeneration in Alzheimer's disease (AD), and GSH depletion follows
      application of exogenous fibrillar amyloid beta (Abeta) peptides in experimental
      systems; these results are commonly cited as evidence of oxidative damage in AD.
      We used MC65 human neuroblastoma cells that conditionally express carboxy
      terminal fragments of the Abeta precursor protein (Abeta/CTFs) to directly test
      the hypothesis that GSH is part of the cellular response to stressors associated
      with Abeta/CTF accumulation and not simply a marker of oxidative damage. Our data
      showed that Abeta/CTFs accumulated by post-translational processes and were
      associated with progressive increases in oxidative damage and cytotoxicity.
      Ethycrinic acid (EA) or diethyl maleate (DEM), reagents that deplete GSH through
      non-specific thiol adduction, gave rise to dose-dependent cytotoxicity that was
      independent of Abeta/CTF expression and minimally responsive to alpha-tocopherol
      (AT). In contrast, buthionine sulfoximine (BSO), a selective inhibitor of GSH
      synthase, not only augmented Abeta/CTF-associated cell death but unexpectedly
      potentiated Abeta/CTF accumulation; both outcomes were completely suppressed by
      AT. These data suggest that antioxidants may serve as 'Abeta targeting' therapies
      that suppress toxic protein aggregation rather than simply acting as downstream
      radical scavengers.

PMID- 15857409
TI  - X-linked mental retardation: further lumping, splitting and emerging phenotypes.
AB  - X-linked mental retardation (XLMR) is a very heterogeneous condition, subdivided
      in two categories mainly based on clinical features: syndromic XLMR (MRXS) and
      non-syndromic XLMR (MRX). Although it was thought that 20-25% of mental
      retardation (MR) in males was caused by monogenetic X-linked factors, recent
      estimations are lower: in the range of 10-12%. The number of identified genes
      involved in XLMR has been rapidly growing in the past years. Subsequently, an
      increasing number of patients and families have been reported in which mutations
      in XLMR genes have been identified. It was observed previously, that mutations in
      several of XLMR genes can result in syndromic and in non-syndromic phenotypes.
      This observation has been confirmed for the more recently identified genes.
      Therefore, in this review, focus has been given on the clinical data and on
      phenotype-genotype correlations for those genes implicated in both non-syndromic
      and syndromic XLMR.

PMID- 15857410
TI  - Demented flies? Using Drosophila to model human neurodegenerative diseases.
AB  - The success of biomedical research in the past few decades has led to dramatic
      improvements in human health and, as a result, increased life expectancy. An
      unexpected consequence, however, has been an increase in the number of age
      related diseases and, in particular, neurodegenerative diseases. Despite their
      prevalence, a therapeutic void exists in part due to an incomplete understanding
      of the biochemical pathogenesis of these diseases. A powerful method that can be
      used to understand the basic mechanisms underlying neurodegenerative diseases is
      to generate animal models based on manipulating the expression of single genes
      that are disease causative. This approach has been facilitated by the fact that
      many neurodegenerative diseases are inherited as autosomal dominant traits such
      that expression of the mutant gene in a model organism might be expected to
      recapitulate the disease. During the past few years, the fruit fly, Drosophila
      melanogaster, has emerged as a powerful tool to model human neurodegenerative
      diseases. Here, we describe the various approaches utilized to create fly models
      of human neurodegenerative disease, and how they can aid in our understanding of
      disease pathogenesis and facilitate drug discovery and testing.

PMID- 15857415
TI  - Psychological and genetic counseling implications for adolescent daughters of
      mothers with breast cancer.
AB  - Adolescent daughters of women with breast cancer (BC) are themselves at risk for
      heritable BC. Although some preliminary evidence suggests this group is at an
      increased risk for emotional problems, evidence is limited to studies with small
      samples and no comparison groups. This study examined psychological and family
      functioning, health attitudes and beliefs about genetic risks in adolescent
      females. A case-comparison design was used to compare 55 mother-daughter pairs in
      which the mother had been treated for BC (BC group) to 55 families from the
      general population (GP). Participants completed an assessment battery measuring
      perceptions of personal risk for BC and attitudes about gene testing for BC
      susceptibility, family functioning, and adolescent psychological adjustment.
      Based on manova, no significant differences were found between the two groups on
      measures of the psychological functioning. However, BC group adolescents reported
      significant (p < 0.01) worries about their future health and genetic risk for BC.
      About 68% of BC adolescents compared with 12% of GP adolescents reported being
      moderately to greatly concerned about their susceptibility to genetic mutations.
      Further, 85% of BC group adolescents believed they were susceptible to BC
      compared with 10% of GP adolescents. The results indicated no evidence of
      emotional, behavioral, or familial distress in these families. However, BC
      adolescents have significant worries about their future health. The results of
      this study demonstrate the need to develop a comprehensive model of care where
      accurate information about genetics and health risks can be provided. The
      adolescents also need support to help them cope and communicate with their
      mothers their worries about BC.

PMID- 15857416
TI  - Communication about genetic testing in families of male BRCA1/2 carriers and non
      carriers: patterns, priorities and problems.
AB  - This qualitative interview study explored the way in which information about
      predictive BRCA1/2 testing and its implications for children is disseminated
      within the families of at-risk men who undergo genetic testing. Twenty-nine in
      depth interviews were carried out with family members [male patients (n = 17),
      their partners (n = 8) and adult children (n = 4)]. These explored the following
      themes: experiences of cancer and genetic testing, decision-making about testing
      and the communication of test results and genetic information within the
      immediate family. The interviews revealed that both male patients and their
      partners perceive themselves, rather than health professionals, as responsible
      for disclosing information about genetic testing and genetic risks to their
      children. Parents described three different communication strategies for the
      disclosure of genetic information to their children: complete openness, limited
      disclosure and total secrecy. The adoption of a particular communication strategy
      was justified in terms of children's rights to information vs their parental
      duties to protect their children from anxiety-provoking information. Some of the
      problems arising from the adoption of different disclosure patterns are
      identified and the implications for clinical practice are discussed.

PMID- 15857418
TI  - Consanguineous marriages in Jordan: why is the rate changing with time?
AB  - The objective of this study was to explore the secular trend in consanguinity in
      Jordan and the subtypes of consanguineous marriages that may be undergoing a
      change. A total of 1032 individuals attending a diabetic clinic in Amman were
      interviewed. The questionnaire provided information on consanguinity status and
      date of marriage among three generations: the persons interviewed, their parents,
      parents of their spouses and their offspring. Data on consanguinity status among
      5401 marriages was obtained. Generations were named generation 1 for marriages
      contracted before 1950, generation 2 for marriages contracted between 1950 and
      1979, and generation 3 for marriages contracted after 1980. For generations 1, 2,
      and 3, first-cousin marriages constituted 20.2, 28.5 and 19.5% of all marriages,
      respectively, while the subtype of paternal parallel first-cousin marriages
      constituted 75.6, 60.3 and 43.3% of all first-cousin marriages, respectively. The
      offspring of first-cousin parents were significantly more prone to marry their
      relatives than the offspring of non-consanguineous parents, with rates of first
      cousin marriages among offspring of first-cousin parents and non-related parents
      constituting 25.3 and 17.1% of all marriages, respectively. For generations 1, 2
      and 3, the average coefficient of inbreeding was 0.0135, 0.02 and 0.0142,
      respectively. In conclusion, first-cousin marriage rate among a representative
      population from Amman showed a significant decline among marriages contracted
      after 1980 compared to marriages contracted between 1950 and 1979, but not to
      marriages contracted before 1950. The proportion of paternal parallel first
      cousins among first-cousin marriages showed a steady decline from one generation
      to the next.

PMID- 15857417
TI  - Molecular screening for microdeletions at 9p22-p24 and 11q23-q24 in a large
      cohort of patients with trigonocephaly.
AB  - Trigonocephaly is a rare form of craniosynostosis characterized by the premature
      closure of the metopic suture. To contribute to a better understanding of the
      genetic basis of metopic synostosis and in an attempt to restrict the candidate
      regions related to metopic suture fusion, we studied 76 unrelated patients with
      syndromic and non-syndromic trigonocephaly. We found a larger proportion of
      syndromic cases in our population and the ratio of affected male to female was
      1.8 : 1 and 5 : 1 in the non-syndromic and syndromic groups, respectively. A
      microdeletion screening at 9p22-p24 and 11q23-q24 was carried out for all
      patients and deletions in seven of them were detected, corresponding to 19.4% of
      all syndromic cases. Deletions were not found in non-syndromic patients. We
      suggest that a molecular screening for microdeletions at 9p22-p24 and 11q23-q24
      should be offered to all syndromic cases with an apparently normal karyotype
      because it can potentially elucidate the cause of trigonocephaly in this subset
      of patients. We also suggest that genes on the X-chromosome play a major role in
      syndromic trigonocephaly.

PMID- 15857419
TI  - Refinement of the chromosome 16 locus for benign familial infantile convulsions.
AB  - Benign familial infantile convulsions (BFIC) is an autosomal dominantly inherited
      partial epilepsy syndrome of early childhood with remission before the age of 3
      years. The syndrome has been linked to loci on chromosomes 1q23, 2q24, 16p12-q12,
      and 19q in various families. The aim of this study was to identify the
      responsible locus in four unrelated Dutch families with BFIC. Two of the tested
      families had pure BFIC; in one family, affected individuals had BFIC followed by
      paroxysmal kinesigenic dyskinesias at later age, and in one family, BFIC was
      accompanied by later-onset focal epilepsy in older generations. Linkage analysis
      was performed for the known loci on chromosomes 1q23, 2q24, 16p12-q12, and 19q.
      The two families with pure BFIC were linked to chromosome 16p12-q12. Using
      recombinants from these and other published families, the chromosome 16-candidate
      gene region was reduced from 21.4 Mb (4.3 cm) to 2.7 Mb (0.0 cm). For the other
      two families, linkage to any of the known loci was unlikely. In conclusion, we
      confirm the linkage of pure BFIC to chromosome 16p12-q12, with further refinement
      of the locus. Furthermore, the lack of involvement of the known loci in two of
      the families indicates further genetic heterogeneity for BFIC.

PMID- 15857420
TI  - Analysis of CRELD1 as a candidate 3p25 atrioventicular septal defect locus
      (AVSD2).

PMID- 15857421
TI  - Homozygosity for L997F in a child with normal clinical and chloride secretory
      phenotype provides evidence that this cystic fibrosis transmembrane conductance
      regulator mutation does not cause cystic fibrosis.

PMID- 15857422
TI  - Mutations found within exon 1 of MECP2 in Danish patients with Rett syndrome.

PMID- 15857424
TI  - Telemedicine for epilepsy: a useful contribution.

PMID- 15857425
TI  - Time-dependent effect of kainate-induced seizures on glutamate receptor GluR5,
      GluR6, and GluR7 mRNA and Protein Expression in rat hippocampus.
AB  - PURPOSE: Glutamate receptor 6 is strongly implicated in human refractory epilepsy
      and in kainic acid (KA)-induced status epilepticus (SE). In vitro pharmacologic
      studies with newer antiepileptic drugs (AEDs) are increasingly indicating the
      role of glutamate receptor 5 (GluR5) in epilepsy. Glutamate receptor 7 (GluR7)
      has been the least investigated in the context of epilepsy. We studied the
      messenger ribonucleic acid (mRNA) and protein expression of GluR5, GluR6, and
      GluR7 in rat hippocampus 72 h, 90 days, and 180 days after KA-induced SE.
      METHODS: SE was induced by injecting KA intraperitoneally (i.p.) into adult rats.
      The hippocampi were isolated 72 h, 90 days, and 180 days after SE. Reverse
      transcription-polymerase chain reaction (RT-PCR) was performed for mRNA
      expression. Western blots determined the protein expression. RESULTS: A
      significant increase was noted in GluR5 expression in KA-treated animals compared
      with controls at 72 h and 180 days, with no significant difference at the
      intervening 90-day point. Protein levels for GluR5 increased at 72 h and remained
      elevated until 180 days. GluR7 mRNA showed a significant decrease at 90 days
      after seizures. Neither the mRNA expression nor the protein levels of GluR6
      differed from controls at any of the times after SE. CONCLUSIONS: KA-induced SE
      leads to an upregulation of GluR5 mRNA and protein and a downregulation of GluR7
      mRNA in rat hippocampus, with no change in GluR6 mRNA or protein expression.

PMID- 15857426
TI  - Inhibition of persistent sodium current fraction and voltage-gated L-type calcium
      current by propofol in cortical neurons: implications for its antiepileptic
      activity.
AB  - PURPOSE: Although it is widely used in clinical practice, the mechanisms of
      action of 2,6-di-isopropylphenol (propofol) are not completely understood. We
      examined the electrophysiologic effects of propofol on an in vitro model of
      epileptic activity obtained from a slice preparation. METHODS: The effects of
      propofol were tested both on membrane properties and on epileptiform events
      consisting of long-lasting, paroxysmal depolarization shifts (PDSs) induced by
      reducing the magnesium concentration from the solution and by adding bicuculline
      and 4-aminopyridine. These results were integrated with a patch-clamp analysis of
      Na(+) and high-voltage activated (HVA) calcium (Ca(2+)) currents from isolated
      cortical neurons. RESULTS: In bicuculline, to avoid any interference by gamma
      aminobutyric acid (GABA)-A receptors, propofol (3-100 microM) did not cause
      significant changes in the current-evoked, sodium (Na(+))-dependent action
      potential discharge. However, propofol reduced both the duration and the number
      of spikes of PDSs recorded from cortical neurons. Interestingly, relatively low
      concentrations of propofol [half-maximal inhibitory concentration (IC(50)), 3.9
      microM) consistently inhibited the "persistent" fraction of Na(+) currents,
      whereas even high doses (< or =300 microM) had negligible effects on the "fast"
      component of Na(+) currents. HVA Ca(2+) currents were significantly reduced by
      propofol, and the pharmacologic analysis of this effect showed that propofol
      selectively reduced L-type HVA Ca(2+) currents, without affecting N or P/Q-type
      channels. CONCLUSIONS: These results suggest that propofol modulates neuronal
      excitability by selectively suppressing persistent Na(+) currents and L-type HVA
      Ca(2+) conductances in cortical neurons. These effects might cooperate with the
      opening of GABA-A-gated chloride channels, to achieve depression of cortical
      activity during both anesthesia and status epilepticus.

PMID- 15857427
TI  - Neocortical and hippocampal changes after multiple pilocarpine-induced status
      epilepticus in rats.
AB  - PURPOSE: Multiple episodes of pilocarpine-induced status epilepticus (SE) in
      developing rats (P7-P9) lead to progressive epileptiform activity and severe
      cognitive impairment in adulthood. The present work studied possible underlying
      abnormalities in the neocortex and hippocampus of pilocarpine-treated animals.
      METHODS: Wistar rats were submitted to pilocarpine-induced SE at P7, P8, and P9,
      and were killed at P35. Immunocytochemistry was performed on 50-microm vibratome
      sections, by using antibodies against nonphosphorylated neurofilament (SMI-311),
      parvalbumin (PV), calbindin (CB), calretinin (CR), and glutamate decarboxylase
      (GAD-65). Ten-micron cryostat sections were processed for immunohistoblot by
      using antibodies against GluR1, GluR2/3, and GluR4 alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid (AMPA) receptor subunits and NR2ab N-methyl-D-aspartate
      (NMDA) receptor subunit. RESULTS: Adult rats submitted to SE at P7-9 showed: (a)
      altered distribution of neocortical interneurons; (b) increased cortical and
      reduced hippocampal GAD-65 expression; and (c) altered expression of hippocampal
      AMPA and NMDA receptors. CONCLUSIONS: We conclude that multiple SE episodes
      during P7-9 generate long-lasting disturbances that underlie behavioral and
      electrographic abnormalities later in life.

PMID- 15857428
TI  - Lack of association between the C3435T polymorphism in the human multidrug
      resistance (MDR1) gene and response to antiepileptic drug treatment.
AB  - PURPOSE: P-glycoprotein (P-gp) has been implicated in the causation of refractory
      epilepsy. The expression and efflux efficiency of P-gp is influenced by a
      polymorphism (C3435T) in the encoding gene (MDR1). Recent evidence suggests that
      the homozygous C-variant, which is associated with higher expression and
      increased activity of P-gp, is more common in patients with pharmacoresistant
      epilepsy. We have investigated the prevalence of this polymorphism in a series of
      patients attending a specialist epilepsy clinic. METHODS: DNA samples were
      obtained from 400 patients, irrespective of seizure type or drug treatment.
      Genotype of the C3435T polymorphism was determined by traditional polymerase
      chain reaction (PCR) followed by restriction digest. Classification of response
      to treatment was determined in a blinded fashion by an independent physician.
      Results were expressed as genotype and allele frequencies per response group and
      compared by logistic regression analysis. RESULTS: In total, 170 patients were
      classified as responders, with > or =12 months seizure freedom on current
      treatment. The remaining 230 patients were classified as nonresponders.
      Comparison of responders and nonresponders revealed no significant difference in
      allele frequency (C vs. T; odds ratio, 1.03; 95% CI, 0.78-1.37; p = 0.83) or
      genotype frequency (CC vs TT; odds ratio, 1.07; 95% CI, 0.60-1.91; p = 0.81).
      Subanalyses of individual seizure types were similarly unremarkable. CONCLUSIONS:
      This study failed to corroborate a previously reported association between the
      C3435T polymorphism in the human MDR1 gene and pharmacoresistant epilepsy.
      Whether the C3435T polymorphism can act as a marker for the natural history of
      treated epilepsy remains to be determined.

PMID- 15857429
TI  - Time course of adverse events in patients with localization-related epilepsy
      receiving topiramate added to carbamazepine.
AB  - PURPOSE: To explore the time course of treatment-emergent adverse events (AEs)
      during topiramate (TPM) adjunctive therapy. METHODS: Post hoc analyses were
      performed by using data from a large (264 subjects) multicenter, double-blind,
      placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ)
      with or without another antiepileptic drug (AED) in adults with treatment
      resistant partial-onset seizures. The daily incidence and mean duration of the
      most common (> or =5% incidence) AEs were calculated for patients completing the
      12-week study. RESULTS: The daily incidence of somnolence, headache, loss of
      appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and
      vertigo peaked during titration and declined to rates similar to that of placebo
      after the target TPM dose had been reached. In contrast, the daily incidence of
      paresthesia increased during titration and was maintained for the study duration.
      Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo),
      but these were the most common AEs associated with treatment discontinuation.
      Patient/investigator reports of weight loss increased gradually over the course
      of the trial, corresponding with the pattern of change in weight measured at
      study visits. CONCLUSIONS: This study demonstrates that most of the more common
      AEs with TPM adjunctive therapy are transient. Patients can be counseled that
      most AEs emerging when TPM is initially added to CBZ can be expected to diminish
      with continued therapy.

PMID- 15857430
TI  - Biting behavior, aggression, and seizures.
AB  - PURPOSE: To describe the semiologic features of aggressive behaviors observed in
      human epileptic seizures with particular reference to the act of biting a
      conspecific. METHODS: We analyzed the biting behavior (BB) and other aggressive
      gestures occurring in a group of 11 patients retrospectively selected from >1,000
      patients subjected to video-EEG/SEEG monitoring for presurgical evaluation of
      drug-resistant seizures. RESULTS: Patients displaying BB showed (a) a male sex
      predominance, (b) heterogeneous etiologies and lesion locations, and (c) seizures
      involving the frontotemporal regions of both hemispheres. The act of biting was a
      rapid motor action, lasting approximately 600 ms, occurring in the context of
      strong emotional arousal, fear, and anger, with various bodily gestures with
      aggressive connotation. BB was mainly a "reflexive" behavior, in that biting acts
      were evoked (both during and after seizures) by actions of people in close
      contact with the patient. The sole intrusion of the examiner's hand in the space
      near the patient's face was effective in triggering BB. Rarely, self-directed or
      object-directed biting acts were not triggered by external stimuli. Intracranial
      data (SEEG) obtained in one subject showed that the amygdala/hippocampal region
      plus the orbitomedial prefrontal cortex had to be involved by ictal activity to
      observe BB. CONCLUSIONS: Anatomic and electrophysiologic data in our patients
      suggest that a model of dual--temporal and frontal--dysfunction could account for
      the occurrence of ictal/postictal BB. Behavioral data suggest also that BB and
      related aggressive gestures can be considered as the emergence of instinctive
      behaviors with an adaptative significance of defense of the peripersonal space.

PMID- 15857431
TI  - Self-reported seizure frequency and time to first event in the seizure monitoring
      unit.
AB  - PURPOSE: To compare seizure frequency reported in the clinic with time to first
      diagnostic event during video-EEG monitoring. The effect of the artificial
      environment of the monitoring unit on self-reported seizure frequency was
      explored. METHODS: The 155 consecutive patients were seen in the Washington
      University Epilepsy Center and subsequently underwent video-EEG monitoring during
      2001. Of these, 112 had a diagnostic event during monitoring; 31 left without
      having a definite event; and 12 could not provide an estimate of seizure
      frequency in the clinic. The time to first event was compared with self-reported
      seizure frequency. The patients were then divided into three equal groups
      (tertiles) based on mean seizure frequency, and time to first seizure was
      compared between groups. Then the numbers of patients staying >7 days without
      ever having an event were compared between the low and high seizure-frequency
      groups. Finally, Kaplan-Meier survival curves were calculated. RESULTS: No
      correlation was found between self-reported seizure rate and time to diagnostic
      event (r= 0.18; p = 0.06). Time to first event was 2.8 days in the low seizure
      frequency group (mean, 2.2/month), 2.1 days in the medium (mean, 8.8/month), and
      2.1 days in the high (mean, 24.1/month) groups, which were not significantly
      different (p = 0.19). Of patients in the low-frequency group, 79% had an event
      within 7 days. CONCLUSIONS: In the artificial environment of the monitoring unit,
      self-reported outpatient seizure frequency is not an accurate predictor of
      duration of video-EEG monitoring required to make a definitive classification of
      clinical events and should not contribute to the decision as to whether to refer
      a patient for monitoring.

PMID- 15857432
TI  - Intracranial EEG substrates of scalp EEG interictal spikes.
AB  - PURPOSE: To determine the area of cortical generators of scalp EEG interictal
      spikes, such as those in the temporal lobe epilepsy. METHODS: We recorded
      simultaneously 26 channels of scalp EEG with subtemporal supplementary electrodes
      and 46 to 98 channels of intracranial EEG in 16 surgery candidates with temporal
      lobe epilepsy. Cerebral discharges with and without scalp EEG correlates were
      identified, and the area of cortical sources was estimated from the number of
      electrode contacts demonstrating concurrent depolarization. RESULTS: We reviewed
      approximately 600 interictal spikes recorded with intracranial EEG. Only a very
      few of these cortical spikes were associated with scalp recognizable potentials;
      90% of cortical spikes with a source area of >10 cm(2) produced scalp EEG spikes,
      whereas only 10% of cortical spikes having <10 cm(2) of source area produced
      scalp potentials. Intracranial spikes with <6 cm(2) of area were never associated
      with scalp EEG spikes. CONCLUSIONS: Cerebral sources of scalp EEG spikes are
      larger than commonly thought. Synchronous or at least temporally overlapping
      activation of 10-20 cm(2) of gyral cortex is common. The attenuating property of
      the skull may actually serve a useful role in filtering out all but the most
      significant interictal discharges that can recruit substantial surrounding
      cortex.

PMID- 15857433
TI  - Entorhinal cortex involvement in human mesial temporal lobe epilepsy: an
      electrophysiologic and volumetric study.
AB  - PURPOSE: Several studies have demonstrated diminution in the volume of entorhinal
      cortex (EC) ipsilateral to the pathologic side in patients with temporal lobe
      epilepsy (TLE). The relation between the degree of EC atrophy and the
      epileptogenicity of this structure has never been directly studied. The purpose
      of the study was to determine whether atrophy of the EC evaluated by the
      quantitative magnetic resonance imaging (MRI) method is correlated with the
      epileptogenicity of this structure in TLE. METHODS: Intracerebral recordings
      (SEEG method) of seizures from 11 patients with mesial TLE were analyzed.
      Seizures were classified according to patterns of onset: pattern 1 was the
      emergence of a low-frequency, high-amplitude rhythmic spiking followed by a tonic
      discharge, and pattern 2 was the emergence of a tonic discharge in the mesial
      structures. A nonlinear measure of SEEG signal interdependencies was used to
      evaluate the functional couplings occurring between hippocampus (Hip) and EC at
      seizure onset. MRI volumetric analysis was performed by using a T(1)-weighted
      three-dimensional gradient-echo sequence in TLE patients and 12 healthy subjects.
      RESULTS: Significant interactions between Hip and Ec were quantified at seizure
      onset. The EC was found to be the leader structure in most of the pattern 2
      seizures. Volumetric measurements of EC demonstrated an atrophy in 63% of
      patients ipsilateral to the epileptic side. A significant correlation between the
      strength of EC-Hip coupling and the degree of atrophy was found. In addition, in
      those patients that had a normal EC volume, the EC was never the leader structure
      in Ec-Hip coupling. CONCLUSIONS: These results validate the potential role of
      volumetry to predict the epileptogenesis of the EC in patients with hippocampal
      sclerosis and MTLE.

PMID- 15857434
TI  - Occipital lobe epilepsy: clinical characteristics, surgical outcome, and role of
      diagnostic modalities.
AB  - PURPOSE: To assess the role of various diagnostic modalities, to identify
      surgical prognostic factors and concordances with presurgical evaluations, and to
      characterize the clinical features of occipital lobe epilepsy (OLE), we studied
      26 patients who were diagnosed as having OLE and underwent epilepsy surgery.
      METHODS: Diagnoses were established by standard presurgical evaluations, which
      included magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission
      tomography (FDG-PET), ictal single-photon emission computed tomography (SPECT),
      scalp video-EEG monitoring, and intracranial EEG monitoring. After epilepsy
      surgery, patients were followed up for >2 years. RESULTS: Sixteen (61.5%) of the
      26 became seizure free after surgery, and another eight patients had a favorable
      outcome. Sixteen of the 26 patients experienced a type of visual aura (i.e.,
      visual hallucination, visual illusion, blindness, or a field defect). Nine
      patients had both automotor seizures and secondary generalized tonic-clonic
      seizures at different times. Interictal EEG showed correctly localizing spikes in
      10 of the 16 patients who became seizure free, and in three of the 10 non-seizure
      free patients. MRI correctly localized the lesion in seven of these 16 seizure
      free patients, and in three of the 10 non-seizure-free patients. FDG-PET
      correctly localized the lesion in eight of the 16 seizure-free patients, and in
      three of nine non-seizure-free patients. Ictal SPECT was performed in 19 patients
      and correctly localized the lesion in only three of 12 seizure-free patients, and
      in four of seven non-seizure-free patients. Ictal EEG correctly localized the
      lesion in 13 of the 16 seizure-free patients, and in five of the 10 non-seizure
      free patients. No significant relation was found between the diagnostic accuracy
      of any modality and surgical outcome. The localizations of epileptogenic zones by
      these different diagnostic methods were complementary. The concordance of three
      or more modalities was significantly observed in seizure-free patients (p =
      0.042). However, no definite relation was observed between the presence of
      lateralizing clinical seizure manifestation and surgical outcome (p = 0.108).
      CONCLUSIONS: Some specific auras indicated an occipital epilepsy onset. Various
      diagnostic methods can be useful to diagnose OLE, and a greater concordance
      between presurgical evaluation modalities indicates a better surgical outcome.

PMID- 15857435
TI  - Quantitative HMRS and MRI volumetry indicate neuronal damage in the hippocampus
      of children with focal epilepsy and infrequent seizures.
AB  - PURPOSE: Seizures induce progressive morphologic and functional changes in
      particular in the hippocampus, but whether and at what stage the hippocampus is
      affected in children with focal, temporal, nonintractable epilepsy is poorly
      known. We have now studied eventual metabolic and volume changes in the
      hippocampus of children with nonsymptomatic focal epilepsy taking antiepileptic
      medication (AEDs) but still having infrequent seizures. METHODS: Quantitative
      proton magnetic resonance spectroscopy ((1)HMRS) and volumetric MRI were used to
      study the hippocampal region of 11 pediatric outpatients (age 10 to 17 years)
      with cryptogenic localization-related epilepsy, and eight healthy volunteers (age
      9 to 16 years) served as controls. The spectra were obtained bilaterally from the
      hippocampi by using the 1.5-T MR imager. The spectral resonance lines of N-acetyl
      group (NA), creatine and phosphocreatine group (Cr), choline-containing compounds
      (Cho), and myoinositol (mI) were analyzed quantitatively. The volume of the
      hippocampus was semiautomatically calculated. RESULTS: The mean concentration of
      NA was significantly decreased both in the focus side (9.02 +/- 2.00 mM) and in
      the nonfocus side (8.88 +/- 2.09 mM) of the patients compared with the controls
      (10.76 +/- 1.86 mM), in particular if the children had a history of generalized
      tonic-clonic seizures. The mean concentrations of Cho, Cr, and mI did not differ
      significantly between the patients and controls. Moreover, the mean hippocampal
      volume of the focus side of patients was significantly reduced compared with that
      of the controls. CONCLUSIONS: Metabolic changes in hippocampi were detected in
      children with nonsymptomatic localization-related epilepsy and infrequent
      seizures. Reduced NA could reflect neuronal metabolic dysfunction and/or neuronal
      damage, as indicated by our volumetric findings.

PMID- 15857436
TI  - Hippocampal sclerosis in severe myoclonic epilepsy in infancy: a retrospective
      MRI study.
AB  - PURPOSE: Severe myoclonic epilepsy in infancy (SMEI; Dravet's syndrome) is a
      malignant epilepsy syndrome characterized by early prolonged febrile convulsions
      (PFCs) with secondary psychomotor delay and a variety of therapy-resistant
      seizures. Although the initial symptoms are repeated PFCs, the MRI performed at
      the onset of disease shows no hippocampal structural abnormalities. We aimed to
      assess clinical and serial MRI data of patients with SMEI with a special
      attention to the temporomedial structures. To our knowledge, this is the first
      systematic MRI study in this disease. METHODS: Clinical and MRI data of all SMEI
      patients treated in our hospitals between 1996 and 2004 were reviewed. RESULTS:
      Twenty-eight MRIs from 14 children (one to four images/patient) were included.
      Age at disease onset was between 3 and 9 months; age at initial MRI was 5 months
      to 13 years. Ten of 14 patients showed hippocampal sclerosis (HS) during the
      course of the disease (nine unilateral, one bilateral). Six of these 10 had a
      normal initial MRI. Age at the first verified HS was between 14 months and 13
      years. Neither complex partial seizures nor anterior temporal irritative zone was
      recorded in these children. CONCLUSIONS: After initially normal structures, in
      most patients with SMEI, HS develops several months or years after the first PFC.
      These data support the hypothesis that PFC might be responsible for HS, but other
      factors and individual sensitivity should play a role in this process.

PMID- 15857437
TI  - Effect of ACTH therapy for epileptic spasms without hypsarrhythmia.
AB  - PURPOSE: We analyzed the short- and long-term effects of adrenocorticotropic
      hormone (ACTH) therapy for patients with epileptic spasms (ESs) who did not meet
      the criteria of West syndrome (WS). METHODS: The subjects were 30 patients,
      including 13 boys and 17 girls, who had received ACTH therapy between 1970 and
      2003. We excluded patients with WS, but included those with a history of WS who
      no longer showed hypsarrhythmia at the period of ACTH therapy. The age at onset
      of ESs and at ACTH therapy ranged from 2 to 82 months with a median of 18 months,
      and from 11 to 86 months with a median of 29 months, respectively. RESULTS:
      Excellent and poor responses were obtained in 19 (63%) and 11 (37%) patients,
      respectively, as a short-term effect. Although the patients could be
      subclassified into five subgroups according to the previous reports, no
      difference was seen in short- term response to ACTH. Among 17 of the 19 patients
      with excellent short-term outcomes and a follow-up of >1 year after the ACTH
      therapy, eight patients have continued to be seizure free (29%; excellent long
      term effect), whereas the remaining nine patients had a recurrence of seizures
      (complex partial seizures, four; generalized tonic seizures, three; ESs, two) at
      9 months to 198 months (median, 49 months) after ACTH therapy. In addition, nine
      of the 17 patients demonstrated a localized frontal EEG focus after the ACTH
      therapy, although most of these had previously shown diffuse epileptic EEG
      abnormality. CONCLUSIONS: ACTH therapy is worth trying for patients with
      resistant ESs, even without features of WS. However, the long-term effect is
      uncertain because recurrences of various types of seizures, including focal, were
      frequently observed.

PMID- 15857438
TI  - Adding video recording increases the diagnostic yield of routine
      electroencephalograms in children with frequent paroxysmal events.
AB  - PURPOSE: To report on the usefulness of adding video recording to routine EEG
      studies of infants and children with frequent paroxysmal events. METHODS: We
      analyzed the efficacy of this diagnostic means during a 4-year period. The
      decision whether to add video recording was made by the pediatric EEG interpreter
      at the time of the study. Studies were planned to last between 20 and 30 min,
      and, if needed, were extended by the EEG interpreter. For most studies, video
      recording was added from the beginning of EEG recording. In a minority of cases,
      the addition of video was implemented during the first part of the EEG test, as
      clinical events became obvious. In these cases, a new study (file) was begun. The
      success rate was analyzed according to the indications for the EEG study:
      paroxysmal eye movements, tremor, suspected seizures, myoclonus, staring
      episodes, suspected stereotypias and tics, absence epilepsy follow-up, cyanotic
      episodes, and suspected psychogenic nonepileptic events. RESULTS: Video recording
      was added to 137 of 666 routine studies. Mean patient age was 4.8 years. The
      nature of the event was determined in 61 (45%) of the EEG studies. Twenty-eight
      percent were hospitalized patients. The average study duration was 26 min. This
      diagnostic means was particularly useful for paroxysmal eye movements, staring
      spells, myoclonic jerks, stereotypias, and psychogenic nonepileptic events. About
      46% of 116 patients for whom cognitive data were available were mentally
      retarded. EEG with added video recording was successfully performed in all 116
      cases and provided useful information in 29 (55%) of these 53 patients.
      CONCLUSIONS: Adding video recording to routine EEG was helpful in 45% of cases
      referred for frequent paroxysmal events. This technique proved useful for
      hospitalized children as well as for outpatients. Moreover, it was successfully
      applied in cognitively impaired patients. Infants and children with paroxysmal
      eye movements, staring spells, myoclonic jerks, stereotypias, and pseudoseizures
      especially benefited from this diagnostic means. Because of its low cost and the
      little discomfort imposed on the patient and his or her family, this technique
      should be considered as a first diagnostic step in children with frequent
      paroxysmal events.

PMID- 15857439
TI  - Depression and anxiety disorders in pediatric epilepsy.
AB  - PURPOSE: This study examined affective disorders, anxiety disorders, and
      suicidality in children with epilepsy and their association with seizure-related,
      cognitive, linguistic, family history, social competence, and demographic
      variables. METHODS: A structured psychiatric interview, mood self-report scales,
      as well as cognitive and language testing were administered to 100 children with
      complex partial seizures (CPSs), 71 children with childhood absence epilepsy
      (CAE), and 93 normal children, aged 5 to 16 years. Parents provided behavioral
      information on each child through a structured psychiatric interview and behavior
      checklist. RESULTS: Significantly more patients had affective and anxiety
      disorder diagnoses (33%) as well as suicidal ideation (20%) than did the normal
      group, but none had made a suicide attempt. Anxiety disorder was the most
      frequent diagnosis among the patients with a diagnosis of affective or anxiety
      disorders, and combined affective/anxiety and disruptive disorder diagnoses, in
      those with suicidal ideation. Only 33% received some form of mental health
      service. Age, verbal IQ, school problems, and seizure type were related to the
      presence of a diagnosis of affective or anxiety disorder, and duration of
      illness, to suicidal ideation. CONCLUSIONS: These findings together with the high
      rate of unmet mental health underscore the importance of early detection and
      treatment of anxiety disorders and suicidal ideation children with CPSs and CAE.

PMID- 15857440
TI  - Screening for major depression in epilepsy with common self-report depression
      inventories.
AB  - PURPOSE: Major depression is a common psychiatric comorbidity in chronic epilepsy
      that is frequently unrecognized and untreated. A variety of self-report mood
      inventories are available, but their validity as well as ability to detect major
      depression in epilepsy remains uncertain. The purpose of this study was to
      determine the ability of two common depressive symptom inventories to identify
      major depression in people with epilepsy. METHODS: In total, 174 adult patients
      with epilepsy underwent standardized psychiatric interview techniques [Mini
      International Neuropsychiatric Interview (MINI) and Mood Disorders module of the
      Structured Clinical Interview for DSM-IV Axis I Disorders-Research Version (SCID
      I)] to determine the presence of current major depression. Subjects completed two
      self-report depression inventories [Beck Depression Inventory-II (BDI-II), Center
      for Epidemiological Study of Depression (CES-D)]. The ability of these self
      report measures to identify major depression as identified by the gold standard
      structured interviews was examined by using diagnostic efficiency statistics.
      RESULTS: Both the BDI-II and the CES-D exhibited significant ability to identify
      major depression in epilepsy. All ROC analyses were highly significant (mean area
      under the curve, 0.92). Mean sensitivity (0.93) and specificity (0.81) were
      strong, with excellent negative predictive value (0.98) but lower positive
      predictive value (0.47). CONCLUSIONS: Common self-report depression measures can
      be used to screen for major depression in clinical settings. Use of these
      measures will assist in the clinical identification of patients with major
      depression so that treatment can be initiated.

PMID- 15857441
TI  - Predictors for negative attitudes toward subjects with epilepsy: a representative
      survey in the general public in Austria.
AB  - PURPOSE: To assess knowledge of and attitudes toward epilepsy in the Austrian
      general public and to identify independent predictors of negative attitudes.
      METHODS: A survey consisting of a representative sample of 2,128 Austrian adults
      was commissioned. A questionnaire similar to the ones used in earlier studies in
      other countries was used. The independent influence of socioeconomic variables
      and of knowledge and concepts about epilepsy on attitudes were analyzed by using
      logistic stepwise regression procedure. RESULTS: Nearly 10% of respondents
      expressed negative attitudes toward people with epilepsy. These figures are
      similar to those of other studies performed in comparable societies. In addition
      to being male and of low socioeconomic background, having little theoretical
      knowledge about epilepsy, misconceptions of epilepsy as a form of insanity, and
      no personal acquaintance with someone with epilepsy independently predispose to
      unfavorable attitudes toward epilepsy. CONCLUSIONS: Information campaigns on
      epilepsy are likely to improve attitudes toward epilepsy when they target
      misconceptions about epilepsy and when they offer opportunities for personal
      acquaintance with people with epilepsy.

PMID- 15857442
TI  - Development of a validated clinical case definition of generalized tonic-clonic
      seizures for use by community-based health care providers.
AB  - PURPOSE: To develop and test a clinical case definition for identification of
      generalized tonic-clonic seizures (GTCSs) by community-based health care
      providers. METHODS: To identify symptoms that can help identify GTCSs, patients
      with history of a jerky movements or rigidity in any part of the body ever in
      life were recruited from three sites: the community, secondary care hospital, and
      tertiary care hospital. These patients were administered a 14-item structured
      interview schedule focusing on the circumstances surrounding the seizure.
      Subsequently, a neurologist examined each patient and, based on available
      investigations, classified them as GTCS or non-GTCS cases. A logistic regression
      analysis was performed to select symptoms that were to be used for case
      definition of GTCSs. Validity parameters for the case definition at different
      cutoff points were calculated in another set of subjects. RESULTS: In total, 339
      patients were enrolled in the first phase of the study. The tertiary care
      hospital contributed the maximal number of GTCS cases, whereas cases of non-GTCS
      were mainly from the community. At the end of phase I, the questionnaire was
      shortened from 14 to eight questions based on statistical association and
      clinical judgment. After phase II, which was conducted among 170 subjects, three
      variables were found to be significantly related to the presence of GTCSs by
      logistic regression: absence of stress (13.1; 4.1-41.3), presence of frothing
      (13.7; 4.0-47.3), and occurrence in sleep (8.3; 2.0-34.9). As a case definition
      using only three variables did not provide sufficient specificity, three more
      variables were added based on univariate analysis of the data (incontinence
      during the episode and unconsciousness) and review of literature (injury during
      episode). A case definition consisting of giving one point to an affirmative
      answer for each of the six questions was tested. At a cutoff point of four,
      sensitivity was 56.9 (47.4-66.0) and specificity, 96.3 (86.2-99.4). Among the 197
      GTCS and 26 new non-GTCS patients recruited from hospitals from select SEAR
      Member Countries, in phase III, the sensitivity of this clinical case definition
      was 72% and specificity, 100%. A stratified analysis by gender in all the three
      phases did not show any differences between the sexes. CONCLUSIONS: Based on
      these criteria, we recommend that all patients with a history of two or more
      episodes of jerking or rigidity of limbs, having a score of > or =4 in the case
      definition, be identified as having GTCSs and started on antiepileptic
      medications. This clinical case definition can be very useful for community-based
      health care providers to identify and manage cases of GTCSs in the community.
      This should play a major role in the reduction of treatment gap for epilepsy in
      developing countries.

PMID- 15857443
TI  - Cost-effectiveness of first-line antiepileptic drug treatments in the developing
      world: a population-level analysis.
AB  - PURPOSE: To establish the population-level costs and cost-effectiveness of first
      line antiepileptic drug (AED) treatments for reducing the treatment gap in
      developing countries. METHODS: A population model was applied to nine World
      Health Organization (WHO) developing subregions to estimate the impact of four
      first-line AEDs in the primary care management of (ICD-10 defined) idiopathic
      epilepsy and epileptic syndromes: phenobarbitone (PB), phenytoin (PHT),
      carbamazepine (CBZ), and valproic acid (VPA). The efficacy of treatment was
      gauged in terms of improvements to both disability and recovery, subsequently
      adjusted for treatment coverage, response, and adherence. Total population-level
      treatment effects (measured in disability-adjusted life years or DALYs averted)
      and treatment costs (measured in international dollars; IUS dollars) were
      combined to form ratios of cost-effectiveness. RESULTS: Across nine developing
      WHO subregions, extending AED treatment coverage to 50% of primary epilepsy cases
      would avert between 150 and 650 DALYs per one million population (equivalent to
      13-40% of the current burden), at an annual cost per capita of IUS dollars 0.20
      1.33. Older first-line AEDs (PB, PHT) were most cost-effective on account of
      their similar efficacy but lower acquisition cost (IUS dollars 800-2,000 for each
      DALY averted). CONCLUSIONS: A significant proportion of the current burden of
      epilepsy in developing countries is avertable by scaling-up the routine
      availability of low-cost AEDs. Critical factors in the successful implementation
      of such a scaled-up level of service delivery, apart from renewed political
      support and investment, relate to appropriate training and continuity of drug
      supply.

PMID- 15857444
TI  - Seizure-associated abnormalities in epilepsy: evidence from MR imaging.
AB  - Acute seizure-associated changes have been described in the animal and human
      literature. Controversy exists over whether seizures cause permanent damage to
      the brain, and whether a (prolonged) seizure can induce changes that lead to an
      epileptic lesion, resulting in habitual seizures and epilepsy. Current magnetic
      resonance imaging (MRI) offers a variety of imaging tools and is capable of
      detecting acute seizure-associated changes. In contrast to the histologic
      examination, serial MRI studies are possible and allow longitudinal observation
      of the fate of these changes. This report reviews the literature on acute seizure
      associated effects emphasizing the MRI evidence.

PMID- 15857445
TI  - A comparison of epilepsy patients in a traditional ambulatory clinic and a
      telemedicine clinic.
AB  - PURPOSE: This article compares a traditional ambulatory clinic in an academic
      medical center with a telemedicine clinic. The telemedicine clinic is a joint
      project of the UTMB Telehealth Center and the Epilepsy Foundation of Southeast
      Texas, with partial funding for clinical operations provided by the Texas
      Department of Health. METHODS: Data were collected on all the patients (n = 155)
      in both clinics for 3 months in 2004. In addition to demographic information,
      outcome data (number of seizures, hospitalizations, and emergency room visits)
      were gathered. Medication compliance also was collected by using self-report and
      medication levels. RESULTS: Outcome variables were subjected to t test and chi(2)
      analysis. No significant differences were found in any of the demographic data or
      outcome measures between the two groups. CONCLUSIONS: Telemedicine is an
      acceptable alternative to in-person clinics for the provision of care to adults
      with epilepsy. Because telemedicine programs are designed to bring medical care
      closer to where patients live, these clinics provide an excellent alternative to
      provide consistent care in rural and geographically isolated areas. Additional
      studies are needed to investigate the potential costs associated with
      telemedicine as well as the potential for cost savings over time as patients are
      more able to access care and therefore may be more likely to seek the needed
      routine care and follow-up.

PMID- 15857446
TI  - Plasma concentrations of risperidone and olanzapine during coadministration with
      oxcarbazepine.
AB  - PURPOSE: Oxcarbazepine (OZC) is a second-generation antiepileptic drug (AED) that
      also may be used as a mood stabilizer. Unlike carbamazepine (CBZ), which is an
      inducer of the cytochrome P-450 isoforms and may accelerate the elimination of
      several therapeutic agents, OXC seems to have only a modest inducing action. The
      aim of this investigation was to evaluate the effect of a treatment with OXC on
      plasma concentrations of the new antipsychotics risperidone and olanzapine.
      METHODS: OXC, at a dosage of 900-1,200 mg/day, was administered for 5 consecutive
      weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years, with bipolar
      or schizoaffective disorder. Twelve patients were stabilized on risperidone
      therapy (2-6 mg/day) and 13 on olanzapine (5-20 mg/day). Steady-state plasma
      concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9
      OH-risperidone) and olanzapine were measured by high-pressure liquid
      chromatography (HPLC) before addition of OXC and after 5 weeks from the start of
      adjunctive treatment. RESULTS: OXC caused only minimal and no significant changes
      in the mean plasma levels of risperidone (from 5.6 +/- 3.6 ng/ml at baseline to
      4.8 +/- 2.6 ng/ml at week 5), 9-OH-risperidone (from 23.6 +/- 7.5 to 24.7 +/- 7.4
      ng/ml), and olanzapine (from 26.5 +/- 5.7 ng/ml at baseline to 27.8 +/- 5.1
      ng/ml). OXC coadministration with either risperidone or olanzapine was well
      tolerated. CONCLUSIONS: Our findings indicate that OXC does not affect the
      elimination of risperidone and olanzapine, thus confirming its weak inducing
      effect on hepatic drug-metabolizing enzymes.

PMID- 15857447
TI  - Levetiracetam concentrations in serum and in breast milk at birth and during
      lactation.
AB  - PURPOSE: To study the pharmacokinetics of levetiracetam (LEV) at birth, during
      lactation, and in the nursed infant. METHODS: Eight consecutive breast-feeding
      women with epilepsy treated with LEV twice daily and their infants were studied.
      RESULTS: The mean umbilical cord serum/maternal serum ratio was 1.14 (range, 0.97
      1.45) (n = 4). The mean milk/maternal serum concentration ratio was 1.00 (range,
      0.76-1.33) at 3 to 5 days after delivery (n = 7). At sampling 2 weeks to 10
      months after delivery (n = 5), it was similar (range, 0.85-1.38). At 3 to 5 days
      after delivery, the infants had very low LEV serum concentrations (<10-15
      microM), a finding that persisted during continued breast-feeding. No
      malformations were detected, and in none of the infants did signs of adverse
      effects develop. CONCLUSIONS: Our data indicate an extensive transfer of LEV from
      mother to fetus and into breast milk. However, breast-fed infants had very low
      LEV serum concentrations, suggesting a rapid elimination of LEV.

PMID- 15857448
TI  - Is variation in the GABA(B) receptor 1 gene associated with temporal lobe
      epilepsy?
AB  - PURPOSE: gamma-Aminobutyric acid (GABA)-receptor genes are prime candidates for a
      role in seizure susceptibility. An association between the c.1465G-->A variant in
      the GABA(B) receptor 1 gene (GABBR1) and susceptibility to temporal lobe epilepsy
      (TLE) has been reported in an Italian cohort. We sought to replicate this
      association in an independent Australian cohort. METHODS: The 234 patients with
      TLE and 164 healthy controls were genotyped for the c.1465G-->A variant, by using
      inclusion criteria identical to those of the first study. RESULTS: The c.1465G-
      >A variant was found in one TLE patient and one control subject. Genotype and
      allele frequencies did not differ between groups. CONCLUSIONS: We did not
      replicate the reported associations between the c.1465G-->A variant and
      susceptibility to TLE. We suggest that the initial positive association may be
      due to undetected population stratification; the importance of genomic control is
      emphasized. Population-specific effects also may play a role, and we highlight
      the need to demonstrate an in vitro functional effect to give biologic meaning to
      any proposed association.

PMID- 15857449
TI  - Deep EEG recordings of the mammillary body in epilepsy patients.
AB  - PURPOSE: To our knowledge, the epileptic and nonepileptic electroencephalographic
      (EEG) discharges recorded within the human mammillary body (MB) and
      mammillothalamic tract (MTT) areas have never been published. Herein, we present
      the EEG recordings from these structures in patients with refractory epilepsy
      (RE). METHODS: Three men (ages 41-43 years) were enrolled in a clinical trial for
      deep brain stimulation (DBS) of MB-MTT in RE. Previous evaluations had
      demonstrated a low likelihood of successful response to medication or resective
      surgery. DBS macroelectrodes were bilaterally implanted within the MB-MTT under
      general anesthesia and their location checked by magnetic resonance imaging
      (MRI). We obtained a surface-depth EEG for a 2- to 4-day period, including
      monitoring of the cardiorespiratory and mnemonic functions. RESULTS: The
      background pattern of EEG recorded from MB-MTT was low-amplitude (usually <25
      microv for MB and <20 microv for MTT) waves with a variable combination of theta
      beta rhythms. In two patients, pseudoperiodic slow spikes were unilaterally
      recorded with or without clinical signs. For one patient, several focal ictal
      discharges were recorded in the right MB without scalp EEG changes. CONCLUSIONS:
      The analysis of our depth EEG revealed that the theta-beta pattern represents the
      predominant physiologic profile of MB. Paroxysmal epileptiform discharges can be
      observed in human MB. These data supplement those available from animal
      observations.

PMID- 15857450
TI  - Visually self-induced seizures sensitive to round objects.
AB  - PURPOSE: To describe a previously unreported type of self-induced pattern
      sensitive seizures in a child. METHODS: Evaluation of clinical and EEG features.
      RESULTS: An 18-month-old boy was initially seen with series of short focal tonic
      seizures self-induced by gazing intermittently at round objects. Self-induction
      of these seizures had an obvious relieving effect on the child. Covering the
      round object foiled further seizures but resulted in a tantrum. Later in the
      course, an increasing variety of patterns proved to be capable of inducing
      seizures, which occurred with increasing frequency and severity, including
      secondarily generalized tonic-clonic seizures. Interictal EEG revealed multifocal
      sharp-and-slow-waves. Ictal EEG showed no abnormalities during short focal
      seizures and rapidly generalizing epileptic discharges during a secondarily
      generalized seizure. No photosensitivity was noted. Motor and mental development
      of the boy stagnated over a period of 2 years. Behavioral therapy as well as
      medical treatment, consisting of various combinations of antiepileptic drugs
      (AEDs) together with a selective serotonin-reuptake inhibitor, were of merely
      transient benefit. Only combined pharmacotherapy, including valproate, sulthiame,
      and clobazam, resulted in seizure control at age 3 years 9 months. CONCLUSIONS:
      Visual capture of geometric patterns other than stripes or gratings may trigger
      focal seizures with secondary generalization. Synchronization of cortical neurons
      responsible for pattern recognition may account for epileptogenesis in this
      child.

PMID- 15857452
TI  - Rosacea and its management: an overview.
AB  - BACKGROUND: Rosacea is a chronic inflammatory disorder that affects 10% of the
      population. The prevalence of rosacea is highest among fair-skinned individuals,
      particularly those of Celtic and northern European descent. Since a cure for
      rosacea does not yet exist, management and treatment regimens are designed to
      suppress the inflammatory lesions, erythema, and to a lesser extent, the
      telangiectasia involved with rosacea. OBJECTIVES: This review outlines the
      treatment options that are available to patients with rosacea. METHODS: Published
      literature involving the treatment or management of rosacea was examined and
      summarized. RESULTS: Patients who find that they blush and flush frequently, or
      have a family history of rosacea are advised to avoid the physiological and
      environmental stimuli that can cause increased facial redness. Topical agents
      such as metronidazole, azelaic acid cream or sulfur preparations are effective in
      managing rosacea. Patients who have progressed to erythematotelangiectatic and
      papulopustular rosacea may benefit from the use of an oral antibiotic, such as
      tetracycline, and in severe or recalcitrant cases, isotretinoin to bring the
      rosacea flare-up under control. Treatment with a topical agent, such as
      metronidazole, may help maintain remission. Patients with ocular involvement may
      benefit from a long-term course of an antibiotic and the use of metronidazole
      gel. A surgical alternative, laser therapy, is recommended for the treatment of
      telangiectasias and rhinophyma. Patients with distraught feelings due to their
      rosacea may consider cosmetic camouflage to cover the signs of rosacea.
      CONCLUSIONS: With the wide variety of oral and topical agents available for the
      effective management of rosacea, patients no longer need to feel self-conscious
      because of their disorder.

PMID- 15857453
TI  - Position paper on diagnosis and treatment of atopic dermatitis.
AB  - The diagnosis of atopic dermatitis (AD) is made using evaluated clinical
      criteria. Management of AD must consider the symptomatic variability of the
      disease. It is based on hydrating topical treatment, and avoidance of specific
      and unspecific provocation factors. Anti-inflammatory treatment is used for
      exacerbation management. Topical corticosteroids remain the first choice.
      Systemic anti-inflammatory treatment should be kept to a minimum, but may be
      necessary in rare refractory cases. The new topical calcineurin inhibitors
      (tacrolimus and pimecrolimus) expand the available choices of topical anti
      inflammatory treatment. Microbial colonization and superinfection (e.g. with
      Staphylococcus aureus, Malassezia furfur) can have a role in disease exacerbation
      and can justify the use of antimicrobials in addition to the anti-inflammatory
      treatment. Evidence for the efficacy of systemic antihistamines in relieving
      pruritus is still insufficient, but some patients seem to benefit. Adjuvant
      therapy includes ultraviolet (UV) irradiation preferably of UVA wavelength; UVB
      311 nm has also been used successfully. Dietary recommendations should be
      specific and only given in diagnosed individual food allergy. Stress-induced
      exacerbations may make psychosomatic counselling recommendable. 'Eczema school'
      educational programmes have proved to be helpful.

PMID- 15857454
TI  - 'Decubital candidosis': a study of 26 cases.
AB  - BACKGROUND: Candidoses are infections caused by yeasts of the genus Candida.
      'Decubital candidosis' is a particular form of cutaneous candidosis that occurs
      on the dorsal skin of chronically bedridden patients; there are very few studies
      about this presentation in the medical literature. OBJECTIVE: To study the
      clinical, mycological and histopathological features of 26 cases of 'decubital
      candidosis' along with factors that may predispose to it. METHODS: Twenty-six
      patients were included and their general characteristics and clinical lesions
      were carefully studied. The presence of candidosis in other organs and the
      occurrence of predisposing factors were searched by reviewing the medical
      records. Mycological studies were performed and cutaneous biopsies were taken.
      RESULTS: Median age of patients was 46 years, 11 were male and 15 were female, 25
      were caucasian, one was Asian and no one was Afro-Carribean. This finding
      suggests a greater resistance of Afro-Carribean skin to this form of candidosis.
      The median time of hospitalization until rash occurrence was 24.8 days. Clinical
      lesions consisted of erythema, erosions, pustules, papules and desquamation. The
      most significant predisposing factors for this eruption were prolonged bedrest
      and broad-spectrum antibiotics. Candidosis on other body sites was diagnosed in
      10 cases and additional specific predisposing factors were observed in all 10.
      Potassium hydroxide examination was a reliable test for diagnosing this disease.
      Candida albicans was the agent in all 26 cases. Spongiform pustules were the most
      significant histopathological findings and yeasts were restricted to the horny
      layer in all biopsied cases. CONCLUSION: 'Decubital candidosis' is probably
      induced by prolonged bedrest and facilitated by long-term use of antibiotics.
      This cutaneous infection does not seem to predispose to systemic candidosis.

PMID- 15857455
TI  - Mucosal vulval lichen planus: outcome, clinical and laboratory features.
AB  - BACKGROUND: Mucosal lichen planus of the vulva is a rare but increasingly
      recognized condition. It has potentially severe complications such as fusion of
      the labia and vagina; the risk of developing squamous cell carcinoma (SCC) may be
      increased. An association between hepatitis B and C infection and skin or oral
      lichen planus appears to exist in certain geographical areas. OBJECTIVE: To
      investigate the course of mucosal vulval lichen planus, its response to treatment
      and associated laboratory features. SUBJECTS AND METHODS: Forty-four women with
      mucosal vulval lichen planus were studied between 1997 and 2000 and laboratory
      data were collected. RESULTS: Thirty of 44 patients had additional oral lesions,
      only nine had cutaneous findings compatible with lichen planus. We did not find
      an association with antibodies to hepatitis B or C virus in this British study
      population. All women were treated with potent to very potent topical
      corticosteroids; however, in the majority of patients symptoms persisted. In
      seven (16%) patients vulval lichen planus was in remission after a disease
      duration between 2 and 18 years (mean 10.6 years). One patient developed a vulval
      SCC. CONCLUSIONS: Screening for hepatitis B and C in women with mucosal vulval
      lichen planus in the UK seems unnecessary. We recommend long-term follow-up, and
      that all non-healing ulcerative and papular lesions should be biopsied.

PMID- 15857456
TI  - Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to
      the skin.
AB  - Hyaluronic acid (HA) is a naturally occurring polyanionic, polysaccharide that
      consists of N-acetyl-D-glucosamine and beta-glucoronic acid. It is present in the
      intercellular matrix of most vertebrate connective tissues especially skin where
      it has a protective, structure stabilizing and shock-absorbing role. The unique
      viscoelastic nature of HA along with its biocompatibility and non-immunogenicity
      has led to its use in a number of clinical applications, which include: the
      supplementation of joint fluid in arthritis; as a surgical aid in eye surgery;
      and to facilitate the healing and regeneration of surgical wounds. More recently,
      HA has been investigated as a drug delivery agent for various routes of
      administration, including ophthalmic, nasal, pulmonary, parenteral and topical.
      In fact, regulatory approval in the USA, Canada and Europe was granted recently
      for 3% diclofenac in 2.5% HA gel, Solaraze, for the topical treatment of actinic
      keratoses, which is the third most common skin complaint in the USA. The gel is
      well tolerated, safe and efficacious and provides an attractive, cost-effective
      alternative to cryoablation, curettage or dermabrasion, or treatment with 5
      fluorouracil. The purpose of this review is to describe briefly the physical,
      chemical and biological properties of HA together with some details of its
      medical and pharmaceutical uses with emphasis on this more recent topical
      application.

PMID- 15857457
TI  - Cannabinoids, loratadine and allopurinol as novel additions to the antipsoriatic
      ammunition.
AB  - As the current antipsoriatic medications are commonly associated with deleterious
      side-effects, a determined search for safer agents, which could be used alone or
      in combination with current antipsoriatic drugs, would be very imperative.
      Psoriasis is believed to be characterized by a type 1 cytokine pattern;
      interferon-gamma, interleukin (IL)-2 and tumour necrosis factor (TNF)-alpha are
      predominantly expressed in this disorder. Nitric oxide, reactive oxygen species,
      histamine, leukotriene B4, and decreased [corrected] keratinocyte cyclic
      adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) ratio are
      supposed to play roles in the pathogenesis of this disorder. Based on the
      immunopathogenesis of psoriasis, this paper introduces three novel, potential
      treatments for this clinical conundrum: (i) cannabinoids, which exert inhibitory
      effects on antigen processing and macrophage/T-cell interaction and also on the
      release of IL-2, TNF-alpha and nitric oxide from immune cells; (ii) loratadine,
      which is an antihistamine capable of increasing [corrected] the cAMP/cGMP ratio
      and the production of leukotriene B4; and (iii) allopurinol, which scavenges free
      radicals, inhibits the production of TNF-alpha, and downregulates the expression
      of intercellular adhesion molecule-1 and P2X7 receptors on monocytes/macrophages,
      which are involved in antigen presentation and production of the inflammatory
      response, respectively. Importantly, allopurinol, especially in combination with
      cyclosporin, has been shown to be effective against experimental autoimmune
      uveitis, which, like psoriasis, is a cell-mediated autoimmune disorder.

PMID- 15857458
TI  - Dermatological manifestations in hepatitis B surface antigen carriers in east
      region of Turkey.
AB  - BACKGROUND AND DESIGN: Various cutaneous disorders associated with hepatitis B
      virus infection have been reported so far. Almost all of them were some peculiar
      eruptions or some disorders mainly based on immune complex reaction. OBJECTIVE:
      The aim of this study was to compare the frequency of all dermatological
      disorders other than genetic ones in hepatitis B surface antigen (HBsAg) carrier
      patients and controls in our geographical area. METHODS: Examinations were made
      on 88 hepatitis B carriers and 84 control patients, including entire skin
      surface, and oral and anogenital mucosa, and all the manifestations that could be
      seen were noted down. RESULTS: While the number of HBsAg carrier patients with
      dermatological disorders was 62 (70.75%), it was only 24 (28.57%) in control
      patients. This seems statistically important: Yates' corrected chi-square test =
      28.5; P = 0.0000001; odds ratio = 6.0 (2.94 < odds ratio < 12.2). The prevalence
      of oral lichen planus and pitted keratolysis in HBsAg carrier group was
      significantly higher than that of controls. We found the duration of positivity
      was not important statistically in the development of the dermatological
      disorders. CONCLUSIONS: HBsAg positivity may induce or cause proneness to oral
      lichen planus and pitted keratolysis with some mechanism that needs to be
      elucidated.

PMID- 15857459
TI  - A double-blind, placebo-controlled study of a commercial Aloe vera gel in the
      treatment of slight to moderate psoriasis vulgaris.
AB  - BACKGROUND: The Aloe vera plant has been used for an array of ailments, including
      skin diseases. Recent experimental research have substantiated the presence of
      biologically active compounds in the gel, but there are few controlled, clinical
      trials to assess the efficacy. OBJECTIVE: To test the effect of a commercial,
      preserved, but otherwise untreated Aloe vera gel in psoriasis. PATIENTS/METHODS:
      Forty-one patients with stable plaque psoriasis were included in a randomized,
      double-blind, placebo-controlled right/left comparison. The study comprised a 2
      week wash-out period followed by a 4-week treatment period with two daily
      applications and follow-up visits after 1 and 2 months. RESULTS: Data on 40
      patients were analysed. The score sum of erythema, infiltration and desquamation
      decreased in 72.5% of the Aloe vera-treated sites compared with 82.5% of the
      placebo-treated areas from week 0 to week 4, which was statistically significant
      in favour of the placebo treatment (P = 0.0197). Fifty-five per cent of the
      patients reported local side-effects, mainly drying up of the skin on test areas.
      CONCLUSIONS: The effect of this commercial Aloe vera gel on stable plaque
      psoriasis was modest and not better than placebo. However, the high response rate
      of placebo indicated a possible effect of this in its own right, which would make
      the Aloe vera gel treatment appear less effective.

PMID- 15857460
TI  - Case-control study to identify melanoma risk factors in the Belgian population:
      the significance of clinical examination.
AB  - BACKGROUND: Although numerous studies have evaluated risk factors associated with
      cutaneous malignant melanoma (CMM), no such study has been carried out in
      Belgium. OBJECTIVES: To identify individuals who are at high risk of developing
      malignant melanoma in Belgium, which could enhance the efficacy of screening
      interventions and avoid unnecessary skin inspections. STUDY
      DESIGN/SETTING/SUBJECTS: We prospectively included patients who were diagnosed
      with invasive malignant melanoma between 1998 and 2001 at the Department of
      Dermatology in a case-control study. Controls were selected from the outpatient
      dermatology clinic. Participants were interviewed and clinically examined by a
      dermatologist. We asked questions concerning most known risk factors associated
      with malignant melanoma such as phenotypical and skin characteristics, and
      environmental and lifestyle exposures. To adjust for confounding variables and to
      estimate odds ratios (ORs) and 95% confidence intervals (CIs), a multivariate
      model was used. RESULTS: Although sunburn in childhood and substantial
      occupational solar exposure were modestly, but significantly, associated with
      malignant melanoma risk, clinical examination yielded several stronger risk
      factors. In a multivariate model, which adjusted for age, gender and skin
      phototype, phenotypical characteristics such as skin, hair and eye colour were
      significantly associated with the development of malignant melanoma. In the
      multivariate model, people with three or more atypical naevi were at more than 10
      fold risk of developing a malignant melanoma (> or = 3 atypical naevi; adjusted
      OR = 11.40, 95% CI = 4.79-17.53) compared to those without an atypical naevus.
      The presence of one or more palpable naevi on the upper extremities or having
      solar lentigines increased the odds of developing malignant melanoma at least
      twofold. CONCLUSIONS: In Belgium, risk factors associated with malignant melanoma
      appear to be in accordance with previous studies. To assess peoples' risk
      profile, clinical skin examination is likely to yield the most important sporadic
      malignant melanoma risk factors. Therefore, focusing screening campaigns on
      individuals with predefined findings on skin self-examination may increase its
      efficacy.

PMID- 15857461
TI  - Acrokeratosis paraneoplastica: Bazex syndrome.
AB  - Bazex syndrome is a paraneoplastic dermatosis characterized by acral psoriasiform
      lesions associated with an underlying neoplasm. We present the case of a 64-year
      old patient that was diagnosed with squamous cell lung carcinoma after being
      evaluated for lesions compatible with paraneoplastic acrokeratosis. With a high
      frequency Bazex syndrome is the earliest marker of an underlying subclinical
      neoplasm. An early suspicion is of the outmost importance in order to perform a
      prompt diagnosis of an underlying malignancy. We propose a diagnostic algorithm
      upon suspicion of acrokeratosis paraneoplastica and review the pathogenesis of
      this entity.

PMID- 15857462
TI  - Persistent serpentine supravenous hyperpigmented eruption associated with
      docetaxel.
AB  - Various mucocutaneous reactions have been reported with the use of systemic
      docetaxel. We describe a 47-year-old man who developed a persistent serpentine
      supravenous hyperpigmented eruption (PSSHE), beginning at the site of docetaxel
      injection and spreading along the superficial venous network in the anterior
      aspect of the right forearm and distal arm. The eruption occurred after the first
      infusion of docetaxel following insufficient venous washing. A second infusion
      was administered through a vein in the other forearm, but this time, abundant
      venous washing was performed and a similar eruption did not occur. To our
      knowledge, this is the second report of docetaxel-induced supravenous
      discoloration and we discussed the terminology and mechanism of this unique
      reaction.

PMID- 15857463
TI  - Non-Hodgkin's lymphoma and auricular hypoplasia: associated with juvenile colloid
      milium or ligneous conjunctivitis?
AB  - The exact nature of amyloid-like hyaline material deposits in the skin is not
      well understood in some disorders. Three of those--ligneous conjunctivitis,
      ligneous periodontitis and colloid milium--have been rarely reported in a same
      patient. We report a case of mucosal and skin deposits of an amyloid-like
      homogeneous material associated with non-Hodgkin's lymphoma and congenital
      auricular hypoplasia. We discussed and reviewed the literature on these unique
      associations to determine whether these are the same pathological process. We
      also noted whether this case represents a new syndrome or a coincidental
      association.

PMID- 15857464
TI  - Kaposi sarcoma associated with lipoedema.
AB  - Lipoedema is a form of lipodistrophy, which consists of abnormal accumulation of
      fat in subcutaneous tissue of the lower limbs. It does not cause any disease and
      it has not been reported association with malignity. We describe a 63-year-old
      woman occurring of Kaposi sarcoma on the lipoedema base.

PMID- 15857465
TI  - Juvenile colloid milium: a case report.
AB  - Juvenile colloid milium is extremely rare, has its onset before puberty, may be
      inherited, may be caused by ultraviolet light, and is thought to result from the
      degeneration of keratinocytes. We report a 7-year-old girl with juvenile colloid
      milium. To the best of our knowledge this is the first reported case in Turkey.

PMID- 15857467
TI  - Adult-onset Still's disease with atypical cutaneous features.
AB  - INTRODUCTION: The diagnosis of adult-onset Still's disease (AOSD) can be very
      difficult. There are no specific tests and reliance is usually placed on a
      symptom complex and the well described typical rash seen in most patients. In
      recent years, however, other cutaneous manifestations of AOSD have been reported
      but these are not so well known. OBSERVATIONS: We report a patient with urticaria
      and fixed plaques and review the other 'atypical' cutaneous findings associated
      with AOSD. CONCLUSIONS: The diagnosis of AOSD can be made in the absence of the
      typical Still's rash but in the presence of other atypical cutaneous features.

PMID- 15857466
TI  - Early detection of cutaneous angiosarcoma of the face and scalp and treatment
      with placitaxel.
AB  - Cutaneous angiosarcoma (AS) of the face and scalp of the elderly is a rare
      malignant tumour with a very poor prognosis. The variable presentation and the
      benign appearance of the cutaneous AS may often delay the correct diagnosis.
      Because it is extremely aggressive, only early detection and treatment can modify
      the prognosis. We describe a case of an old man who was diagnosed of AS of the
      face and scalp 1 month after developing the cutaneous lesion. After treatment
      with placitaxel, the lesion completely diminished. Unfortunately, he developed
      pulmonary fibrosis and died 6 months after diagnosis. Predisposing factors of
      this entity are also discussed.

PMID- 15857468
TI  - Perianal ulceration: a case of tuberculosis cutis orificialis.
AB  - BACKGROUND: Tuberculosis cutis orificialis is an extremely rare variant of
      cutaneous tuberculosis. Perianal location is a possible site of presentation.
      METHODS: We describe the management of a young male with a painless non-specific
      perianal ulcer, who presented an asymptomatic disseminate pulmonary and
      intestinal tuberculosis. He had a history of pulmonary sarcoidosis and long-term
      corticosteroid therapy. RESULTS: Healing of the ulcer was achieved after three
      drug antituberculous therapy, with an improvement of the radiographic pulmonary
      alterations. CONCLUSIONS: Tuberculous origin should be considered in persistent
      perianal ulcers to avoid delays in the treatment of this rare form of
      tuberculosis.

PMID- 15857469
TI  - Hobnail haemangioma associated with the menstrual cycle.
AB  - We report the third case in the literature of a hobnail haemangioma with cyclic
      changes throughout the menstrual cycle in a 36-year-old woman, suggesting a
      hormonal basis for the variations in the tumour. This patient was under oral
      contraceptive treatment due to ovarian endometriosis, making the clinical
      diagnosis difficult.

PMID- 15857470
TI  - Progressive and extensive hypomelanosis and extensive pityriasis alba: same
      disease, different names?
AB  - We report the cases of five female patients with high skin phototype affected by
      relapsing, hypochromic, non-scaling macules occurring after the summer on the
      back and spreading over large areas of skin. Histological features disclosed
      decreased epidermal melanin. Psoralen plus ultraviolet A (PUVA) treatment proved
      to be beneficial, but new relapses were noted after stopping treatment. Clinical
      and histological features were consistent with the diagnosis of 'progressive and
      extensive hypomelanosis' described by Guillet in persons of mixed racial
      background. We discuss the differential diagnosis of the latter entity with
      respect to the other idiopathic acquired primitive hypomelanosis and hypothesize
      an overlapping with the so-called extensive pityriasis alba (EPA).

PMID- 15857471
TI  - Simultaneous occurrence of pure red cell aplasia and papular-purpuric 'gloves and
      socks' syndrome in parvovirus B-19 infection.
AB  - Papular-purpuric 'gloves and socks' syndrome (PPGSS) has been associated with
      parvovirus B-19 infection. We report a case of an adult immunocompetent male who
      presented with PPGSS. Bone marrow examination revealed pure red cell aplasia.
      Parvovirus B-19 DNA was detected by polymerase chain reaction in the patient's
      serum, whole blood and in the cutaneous lesions. This report illustrates the
      variety of clinical manifestations caused by B-19 infection, presents for the
      first time the concurrent appearance of pure red cell aplasia and PPGSS in the
      same patient and, finally, suggests that PPGSS may be due to direct lytic effect
      of the virus.

PMID- 15857472
TI  - Clinico-pathological analysis of the cutaneous lesions of a patient with type I
      pseudohypoaldosteronism.
AB  - The autosomal recessive form of type I pseudohypoaldosteronism (PHA-I) is an
      unusual disorder characterized by aldosterone resistance at the target organs,
      which leads to an excessive loss of sodium chloride through urine, sweat and
      saliva, among other secretions. Such a high concentration of salt in the sweat
      during the depletive crises directly causes inflammation and damage in the
      eccrine structures, with cutaneous lesions similar to those appearing in miliaria
      rubra. We report an autosomal recessive PHA-I in a 4-year-old girl, with
      cutaneous lesions mimicking miliaria rubra, that improved after treatment with
      astringent solutions and avoidance of profuse sweating.

PMID- 15857473
TI  - Psoriasis and Brooke-Spiegler syndrome with multiple malignancies.

PMID- 15857474
TI  - Cutaneous necrosis during paroxysmal nocturnal haemoglobinuria: role of
      parvovirus B19?

PMID- 15857475
TI  - Sweet's syndrome and polycythaemia vera.

PMID- 15857476
TI  - An unusual presentation of a common skin pathology at an uncommon site.

PMID- 15857477
TI  - Neurofibromatosis associated with psoriasis.

PMID- 15857478
TI  - Are we starting to induce skin cancer in order to avoid topical steroids?

PMID- 15857479
TI  - Acute depression from isotretinoin. Another case.

PMID- 15857480
TI  - Effects of ultraviolet irradiation on mediator release from basophils and mast
      cells.

PMID- 15857481
TI  - Grover's disease (transient acantholytic dermatosis) associated with atopy.

PMID- 15857482
TI  - Spitz naevus: a proposal for management.

PMID- 15857483
TI  - Topical immunotherapy with diphencyprone in the treatment of extensive and/or
      long-lasting alopecia areata.

PMID- 15857484
TI  - Incontinentia pigmenti: a case with an unusual course.

PMID- 15857485
TI  - Diffuse cutaneous eruption due to interferon alfa and ribavirin treatment of
      chronic hepatitis C.

PMID- 15857486
TI  - Has Helicobacter pylori eradication therapy any effect on severity of rosacea
      symptoms?

PMID- 15857487
TI  - Adverse drug events occurring following hospital discharge.
AB  - OBJECTIVE: To describe the incidence of adverse drug events (ADEs), preventable
      ADEs, and ameliorable ADEs occurring after hospital discharge and their
      associated risk factors. DESIGN: Prospective cohort study. SETTING: Urban
      academic health sciences center. PATIENTS: Consecutive patients discharged home
      from the general medical service. INTERVENTIONS: We determined posthospital
      outcomes approximately 24 days following discharge by performing a chart review
      and telephone interview. Using the telephone interview, we identified new or
      worsening symptoms, the patient's health system use, and recollection of
      processes of care. Posthospital outcomes were judged by 2 internists
      independently. RESULTS: Four hundred of 581 potentially eligible patients were
      evaluated. Of the 400 patients, 45 developed an ADE (incidence, 11%; 95%
      confidence interval [CI], 8% to 14%). Of these, 27% were preventable and 33% were
      ameliorable. Injuries were significant in 32 patients, serious in 6, and life
      threatening in 7. Patients were less likely to experience an ADE if they recalled
      having side effects of prescribed medications explained (OR, 0.4; 95% CI, 0.2 to
      0.8). The risk of ADE per prescription was highest for corticosteroids,
      anticoagulants, antibiotics, analgesics, and cardiovascular medications. Risk
      increased with prescription number. Failure to monitor was an especially common
      cause of preventable and ameliorable ADEs. CONCLUSION: Following discharge, ADEs
      were common and many were preventable or ameliorable. Medication side effects
      should be discussed, and interventions should include better monitoring and
      target patients receiving specific drug classes or multiple medications.

PMID- 15857488
TI  - Seasonal variation in undiagnosed HIV infection on the general medicine and
      trauma services of two urban hospitals.
AB  - OBJECTIVE: To examine the seroprevalence of undiagnosed HIV and variation by
      season among patients admitted to the general internal medicine (GIM) and trauma
      services of two urban hospitals. DESIGN: A cross-sectional blinded HIV-1
      seroprevalence survey. SETTING: A 725-bed academic medical center's hospital and
      an affiliated 324-bed tertiary care hospital. PARTICIPANTS: Residual serological
      specimens were obtained for unique patients aged 17 to 65 to study services in
      summer (June 16 to September 4, 2001) and fall to winter (November 1, 2001 to
      January 8, 2002). METHODS: Hospital files provided data on demographics, service
      type, and discharge clinical categories (fall-winter group only). HIV ELISA
      (enzyme-linked immunosorbent assay) tests with confirmatory Western blot were
      linked to subjects' de-identified files. We excluded 34 subjects with known HIV.
      Of the remaining unique admissions in summer (n=604) and fall-winter (n=978), 60%
      and 55% were tested, respectively. Predictors of undiagnosed HIV infection were
      examined using multivariate analysis. RESULTS: The summer cohort (n=362) had
      significantly lower unadjusted seroprevalence of undiagnosed HIV infection (1.4%;
      95% confidence interval [CI], 0.4% to 3.2%) than the fall-winter cohort (n=539;
      3.7%; 95% CI, 2.3% to 5.7%; P=.04). Overall, undiagnosed HIV was somewhat less
      likely in women (adjusted odds ratio [AOR], 0.45; 95% CI, 0.19 to 1.07) but more
      likely in black patients (AOR, 3.46; 95% CI, 0.70 to 17.06). In the fall-winter
      cohort, undiagnosed HIV was more likely for discharges with the following
      clinical categories versus those with a cardiac condition: dermatologic/breast
      (AOR, 14.90; 95% CI, 1.20 to 184.77), renal/urological (AOR, 22.43; 95% CI, 2.12
      to 236.75), or infectious (AOR, 31.08; 95% CI, 2.40 to 402.98). CONCLUSIONS: The
      higher seroprevalence of undiagnosed HIV in the fall-winter admissions to GIM and
      trauma services supports especially targeting HIV testing in these months.

PMID- 15857489
TI  - Laboratory safety monitoring of chronic medications in ambulatory care settings.
AB  - OBJECTIVE: To evaluate laboratory safety monitoring in patients taking selected
      chronic prescription drugs. DESIGN: Retrospective study using 1999-2001 claims
      data to calculate rates of missed laboratory tests (potential laboratory
      monitoring errors). Eleven drugs/drug groups and 64 laboratory tests were
      evaluated. SETTING: Two staff/network model health maintenance organizations.
      PATIENTS: Continuously enrolled health plan members age> or =19 years taking > or
      =1 chronic medications. MEASUREMENTS AND MAIN RESULTS: Among patients taking
      chronic medications (N=29,823 in 1999, N=32,423 in 2000, and N=36,811 in 2001),
      47.1% in 1999, 45.0% in 2000, and 44.0% in 2001 did not receive > or =1 test
      recommended for safety monitoring. Taking into account that patients were
      sometimes missing more than 1 test for a given drug and that patients were
      frequently taking multiple drugs, the rate of all potential laboratory monitoring
      errors was 849/1,000 patients/year in 1999, 810/1,000 patients/year in 2000, and
      797/1,000 patients/year in 2001. Rates of potential laboratory monitoring errors
      varied considerably across individual drugs and laboratory tests. CONCLUSIONS:
      Lapses in laboratory monitoring of patients taking selected chronic medications
      were common. Further research is needed to determine whether, and to what extent,
      this failure to monitor patients is associated with adverse clinical outcomes.

PMID- 15857490
TI  - Do physicians know when their diagnoses are correct? Implications for decision
      support and error reduction.
AB  - OBJECTIVE: This study explores the alignment between physicians' confidence in
      their diagnoses and the "correctness" of these diagnoses, as a function of
      clinical experience, and whether subjects were prone to over-or underconfidence.
      DESIGN: Prospective, counterbalanced experimental design. SETTING: Laboratory
      study conducted under controlled conditions at three academic medical centers.
      PARTICIPANTS: Seventy-two senior medical students, 72 senior medical residents,
      and 72 faculty internists. INTERVENTION: We created highly detailed, 2-to 4-page
      synopses of 36 diagnostically challenging medical cases, each with a definitive
      correct diagnosis. Subjects generated a differential diagnosis for each of 9
      assigned cases, and indicated their level of confidence in each diagnosis.
      MEASUREMENTS AND MAIN RESULTS: A differential was considered "correct" if the
      clinically true diagnosis was listed in that subject's hypothesis list. To assess
      confidence, subjects rated the likelihood that they would, at the time they
      generated the differential, seek assistance in reaching a diagnosis. Subjects'
      confidence and correctness were "mildly" aligned (kappa=.314 for all subjects,
      .285 for faculty, .227 for residents, and .349 for students). Residents were
      overconfident in 41% of cases where their confidence and correctness were not
      aligned, whereas faculty were overconfident in 36% of such cases and students in
      25%. CONCLUSIONS: Even experienced clinicians may be unaware of the correctness
      of their diagnoses at the time they make them. Medical decision support systems,
      and other interventions designed to reduce medical errors, cannot rely
      exclusively on clinicians' perceptions of their needs for such support.

PMID- 15857491
TI  - Teaching evidence-based medicine skills can change practice in a community
      hospital.
AB  - OBJECTIVES: Several studies have evaluated whether evidence-based medicine (EBM)
      training courses can improve skills such as literature searching and critical
      appraisal but to date, few data exist on whether teaching EBM skills and
      providing evidence-based resources result in change in behavior or clinical
      outcomes. This study was conducted to evaluate whether a multifaceted EBM
      intervention consisting of teaching EBM skills and provision of electronic
      evidence resources changed clinical practice. DESIGN: Before/after study.
      SETTING: The medical inpatient units at a district general hospital.
      PARTICIPANTS: Thirty-five attending physicians and 12 medicine residents.
      INTERVENTION: A multicomponent EBM intervention was provided including an EBM
      training course of seven 1-hour sessions, an EBM syllabus and textbook, and
      provision of evidence-based resources on the hospital network. MEASUREMENTS AND
      MAIN RESULTS: The primary outcome of the study was the quality of evidence in
      support of therapies initiated for the primary diagnoses in 483 consecutive
      patients admitted during the month before and the month after the intervention.
      Patients admitted after implementation of the EBM intervention were significantly
      more likely to receive therapies proven to be beneficial in randomized controlled
      trials (62% vs 49%; P= .016). Of these trial-proven therapies, those offered
      after the EBM intervention were significantly more likely to be based on high
      quality randomized controlled trials (95% vs 87%; P= .023). CONCLUSIONS: A
      multifaceted intervention designed to teach and support EBM significantly
      improved evidence-based practice patterns in a district general hospital.

PMID- 15857492
TI  - Methadone medical maintenance in primary care. An implementation evaluation.
AB  - BACKGROUND: Methadone is effective treatment for opioid addiction, but
      regulations restrict its use. Methadone medical maintenance treats stabilized
      methadone patients in a medical setting, but only experimental programs have been
      studied. OBJECTIVE: To evaluate the implementation of the first methadone medical
      maintenance program established outside a research setting. DESIGN: One-year
      program evaluation. SETTING: A public hospital and a community opioid treatment
      program. PARTICIPANTS: Methadone patients with >1 year of clinical stability.
      Eleven generalist physicians and 4 hospital pharmacists. INTERVENTIONS:
      Regulatory exemptions were requested. Physicians and pharmacists were trained.
      Patients were transferred to the medical setting and permitted 1-month supplies
      of methadone. MEASUREMENTS: Patient eligibility and willingness to enroll,
      treatment retention, urine toxicology results, change in addiction severity and
      functional status, medical services provided, patient and physician satisfaction,
      and physician attitudes toward methadone maintenance. RESULTS: Regulatory
      exemptions were obtained after a 14-month process, and the program was cited in
      federal policy as acceptable for widespread implementation. Forty-nine of 684
      patients (7.2%) met stability criteria, and 30 enrolled. Twenty-eight were
      retained for 1 year, and 2 transferred to other programs. Two patients had opioid
      positive urine tests and were managed in the medical setting. Previously unmet
      medical needs were addressed, and the Addiction Severity Index (ASI) medical
      composite score improved over time (P=.02). Patient and physician satisfaction
      were high, and physician attitudes toward methadone maintenance treatment became
      more positive (P=.007). CONCLUSIONS: Methadone medical maintenance is complex to
      arrange but feasible outside a research setting, and can result in good clinical
      outcomes.

PMID- 15857493
TI  - The impact of comorbidities on hormone use. After the 2000 release of the Women's
      Health Initiative.
AB  - OBJECTIVE: Determine the impact of fracture, coronary disease, and diabetes on
      changes in rates of discontinuation and initiation of estrogen therapy with (EPT)
      and without (ET) progestin, before (September 1, 1999 to June 30, 2002, baseline)
      versus 5 months after (follow-up) release of the Women's Health Initiative EPT
      trial results (WHI). DESIGN, SETTING, AND PARTICIPANTS: Observational cohort;
      169,586 women 40 to 80 years old from 5 U.S. HMOs. METHODS: We used pharmacy data
      to identify ET and EPT users. A woman was a user any month she filled > or =1
      estrogen prescription and in subsequent months based upon the number of
      pills/patches dispensed. We used inpatient and outpatient claims to identify
      fracture January 1, 1999 to June 30, 2002 and pharmacy data to identify disease
      based groups of medications for diabetes and cardiovascular disease. MEASURES:
      EPT/ET prevalence, initiation, and discontinuation rates. RESULTS: Baseline to
      follow-up EPT and ET prevalence declined 45% and 22%, respectively, with no
      difference by comorbidity. Follow-up EPT initiation was half the baseline rate
      irrespective of comorbidity. Compared to baseline, follow-up EPT discontinuation
      rates increased among women with diabetes (relative risk [RR], 6.9; 95%
      confidence interval [CI], 5.6 to 8.4), cardiovascular disease (RR, 5.5; 95% CI,
      4.9 to 6.2), fracture (RR, 3.8; 95% CI, 2.4 to 5.7), and no comorbidity (RR, 4.4;
      95% CI, 3.9 to 4.9). The RRs for follow-up versus baseline EPT discontinuation
      were higher among women with diabetes (P<.01) and cardiovascular disease (P<.01)
      versus women without these comorbidities. ET discontinuation rates among these
      same groups were elevated 2- to 2.8-fold. CONCLUSIONS: Diabetes and
      cardiovascular disease were associated with higher EPT discontinuation rates post
      WHI compared to women without comorbidity; comorbidity had little impact on
      changes in prevalence or initiation of ET/EPT after release of the WHI.

PMID- 15857494
TI  - Resident and faculty perceptions of conflict of interest in medical education.
AB  - OBJECTIVE: To determine resident and faculty perceptions of the pharmaceutical
      industry's influence on medical education. DESIGN, SETTING, AND PARTICIPANTS:
      Anonymous survey of categorical residents and faculty in the department of
      medicine at a large, Midwestern, urban, independent academic medical center. MAIN
      RESULTS: Eighty-one residents (69.2%) and 196 faculty (75.7%) responded to the
      survey. Residents believed that a significantly higher percentage of primary care
      and subspecialist faculty receives industry income or gifts compared to faculty
      respondents. Many faculty, and to a significantly greater degree residents,
      indicated that income or gifts influence the teaching of both internal attending
      physicians and visiting faculty in a variety of educational settings. The
      majority of residents (61.7%) and faculty (62.2%) believed that annual income or
      gifts less than $10,000 could influence an attending physician's teaching. Most
      residents (65.4%) and faculty (74%) preferred that lecturers report all financial
      relationships with industry regardless of which relationships the lecturer
      believes are relevant. CONCLUSIONS: Most internal medicine residents and their
      faculty perceive that industry influences teaching in different educational
      settings, and want teachers to disclose all of their financial relationships with
      industry. This information may guide further development of policies and
      curricula addressing industry relationships within graduate medical education.

PMID- 15857495
TI  - Impact of the Cancer Risk Intake System on patient-clinician discussions of
      tamoxifen, genetic counseling, and colonoscopy.
AB  - The Cancer Risk Intake System (CRIS), a computerized program that "matches"
      objective cancer risks to appropriate risk management recommendations, was
      designed to facilitate patient-clinician discussion. We evaluated CRIS in primary
      care settings via a single-group, self-report, pretest-posttest design.
      Participants completed baseline telephone surveys, used CRIS during clinic
      visits, and completed follow-up surveys 1 to 2 months postvisit. Compared with
      proportions reporting having had discussions at baseline, significantly greater
      proportions of participants reported having discussed tamoxifen, genetic
      counseling, and colonoscopy, as appropriate, after using CRIS. Most (79%)
      reported CRIS had "caused" their discussion. CRIS is an easily used, disseminable
      program that showed promising results in primary care settings.

PMID- 15857496
TI  - Completing a scholarly project during residency training. Perspectives of
      residents who have been successful.
AB  - BACKGROUND: Resident research has potential benefits and scholarly activity is an
      internal medicine residency training requirement. This study sought to learn
      about the resources needed and the barriers to performing scholarly work during
      residency from residents who had been successful. METHODS: A questionnaire was
      delivered to 138 internal medicine residents presenting their work at the 2002
      American College of Physicians-American Society of Internal Medicine annual
      session. Residents were asked to comment on why they had participated in a
      scholarly project, the skills and resources needed to complete the project, as
      well as the barriers. Comparisons were made between residents who presented a
      research abstract and those who exhibited a clinical vignette. RESULTS: Seventy
      three residents (53%) completed the questionnaire. Thirty-nine residents
      presented a clinical vignette and 34 displayed a research abstract. Residents
      participated in research for a variety of reasons, including intellectual
      curiosity (73%), career development (60%), and to fulfill a mandatory scholarly
      activity requirement at their residency program (32%). The most common barriers
      were insufficient time (79%), inadequate research skills (45%), and lack of a
      research curriculum (44%). Residents who had presented research abstracts devoted
      more time (median, 200 vs 50 hours; P<.05) to their project than those who
      exhibited clinical vignettes. Sixty-nine percent of residents thought research
      should be a residency requirement. CONCLUSIONS: The majority of respondents
      reported that their scholarly project was a worthwhile experience despite
      considerable barriers. Teaching research skills more explicitly with a focused
      curriculum and providing adequate protected time may enable residents to be
      successful.

PMID- 15857497
TI  - Strangers or friends? A proposal for a new spirituality-in-medicine ethic.
AB  - We argue that debate regarding whether and how physicians should engage religious
      concerns has proceeded under inadequate terms. The prevailing paradigm approaches
      dialogue regarding religion as a form of therapeutic technique, engaged by one
      stranger, the physician, upon another stranger, the patient. This stranger
      technique framework focuses the debate on questions of physicians' competence,
      threats to patients' autonomy, and neutrality regarding religion, and in so
      doing, it too greatly circumscribes the scope of physician-patient dialogue. In
      contrast, we argue that dialogue regarding religion is better approached as a
      form of philosophical discourse about ultimate human concerns. Such moral
      discourse is often essential to the patient-physician relationship, and rather
      than shrinking from such discourse, physicians might engage patients regarding
      religious concerns guided by an ethic of moral friendship that seeks the
      patient's good through wisdom, candor, and respect.

PMID- 15857500
TI  - The hospitalist movement.

PMID- 15857502
TI  - Spirituality, medicine, and the possibility of wisdom.

PMID- 15857503
TI  - The minimally invasive open video-assisted approach in surgical thyroid diseases.
AB  - BACKGROUND: The targets of minimally invasive surgery (MIVA) could be summarised
      by: achievement of the same results as those obtained with traditional surgery,
      less trauma, better post-operative course, early discharge from hospital and
      improved cosmetic results. The minimally invasive techniques in thyroid surgery
      can be described as either endoscopic "pure" approach (completely closed approach
      with or without CO2 insufflation), or "open approach" with central neck mini
      incision or "open video-assisted approach". Traditionally, open thyroidectomy
      requires a 6 to 8 cm, or bigger, transverse wound on the lower neck. The
      minimally invasive approach wound is much shorter (1.5 cm for small nodules, up
      to 2-3 cm for the largest ones, in respect of the exclusion criteria) upon the
      suprasternal notch. Patients also experience much less pain after MIVA surgery
      than after conventional thyroidectomy. This is due to less dissection and
      destruction of tissues. Pathologies treated are mainly nodular goiter; the only
      kind of thyroid cancer which may be approached with endoscopic surgery is a small
      differentiated carcinoma without lymph node involvement. The patients were
      considered eligible for MIVA hemithyroidectomy and thyroidectomy on the basis of
      some criteria, such as gland volume and the kind of disease. In our experience we
      have chosen the minimally invasive open video-assisted approach of Miccoli et al.
      (2002). The aim of this work was to verify the suitability of the technique and
      the applicability in clinical practice. METHODS: A completely gasless procedure
      was carried out through a 15-30 mm central incision about 20 mm above the sternal
      notch. Dissection was mainly performed under endoscopic vision using conventional
      endoscopic instruments. The video aided group included 11 patients. All patients
      were women with a average age of 54. RESULTS: We performed thyroidectomy in 8
      cases and hemithyroidectomy in 3 cases. The operative average time has been 170
      minutes. CONCLUSION: Nowadays this minimally invasive surgery, in selected
      patients, clearly demonstrates excellent results regarding patient cure rate and
      comfort, with shorter hospital stay, reduced postoperative pain and most
      attractive cosmetic results.

PMID- 15857504
TI  - In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast
      cancer cell line.
AB  - BACKGROUND: Inflammatory breast cancer (IBC) is the most lethal form of locally
      invasive breast cancer known. However, very little information is available on
      the cellular mechanisms responsible for manifestation of the IBC phenotype. To
      understand the unique phenotype of IBC, we compared the motile and adhesive
      interactions of an IBC cell line, SUM 149, to the non-IBC cell line SUM 102.
      RESULTS: Our results demonstrate that both IBC and non-IBC cell lines exhibit
      similar adhesive properties to basal lamina, but SUM 149 showed a marked increase
      in adhesion to collagen I. In vitro haptotaxis assays demonstrate that SUM 149
      was less invasive, while wound healing assays show a less in vitro migratory
      phenotype for SUM 149 cells relative to SUM 102 cells. We also demonstrate a role
      for Rho and E-cadherin in the unique invasive phenotype of IBC. Immunoblotting
      reveals higher E-cadherin and RhoA expression in the IBC cell line but similar
      RhoC expression. Rhodamine phalloidin staining demonstrates increased formation
      of actin stress fibers and larger focal adhesions in SUM 149 relative to the SUM
      102 cell line. CONCLUSION: The observed unique actin and cellular architecture as
      well as the invasive and adhesive responses to the extracellular matrix of SUM
      149 IBC cells suggest that the preference of IBC cells for connective tissue,
      possibly a mediator important for the vasculogenic mimicry via tubulogenesis seen
      in IBC pathological specimens. Overexpression of E-cadherin and RhoA may
      contribute to passive dissemination of IBC by promoting cell-cell adhesion and
      actin cytoskeletal structures that maintain tissue integrity. Therefore, we
      believe that these findings indicate a passive metastatic mechanism by which IBC
      cells invade the circulatory system as tumor emboli rather than by active
      migratory mechanisms.

PMID- 15857505
TI  - Some statistical properties of regulatory DNA sequences, and their use in
      predicting regulatory regions in the Drosophila genome: the fluffy-tail test.
AB  - BACKGROUND: This paper addresses the problem of recognising DNA cis-regulatory
      modules which are located far from genes. Experimental procedures for this are
      slow and costly, and computational methods are hard, because they lack positional
      information. RESULTS: We present a novel statistical method, the "fluffy-tail
      test", to recognise regulatory DNA. We exploit one of the basic informational
      properties of regulatory DNA: abundance of over-represented transcription factor
      binding site (TFBS) motifs, although we do not look for specific TFBS motifs, per
      se . Though overrepresentation of TFBS motifs in regulatory DNA has been
      intensively exploited by many algorithms, it is still a difficult problem to
      distinguish regulatory from other genomic DNA. CONCLUSION: We show that, in the
      data used, our method is able to distinguish cis-regulatory modules by exploiting
      statistical differences between the probability distributions of similar words in
      regulatory and other DNA. The potential application of our method includes
      annotation of new genomic sequences and motif discovery.

PMID- 15857506
TI  - Development of a lung slice preparation for recording ion channel activity in
      alveolar epithelial type I cells.
AB  - BACKGROUND: Lung fluid balance in the healthy lung is dependent upon finely
      regulated vectorial transport of ions across the alveolar epithelium.
      Classically, the cellular locus of the major ion transport processes has been
      widely accepted to be the alveolar type II cell. Although evidence is now
      emerging to suggest that the alveolar type I cell might significantly contribute
      to the overall ion and fluid homeostasis of the lung, direct assessment of
      functional ion channels in type I cells has remained elusive. METHODS: Here we
      describe a development of a lung slice preparation that has allowed positive
      identification of alveolar type I cells within an intact and viable alveolar
      epithelium using living cell immunohistochemistry. RESULTS: This technique has
      allowed, for the first time, single ion channels of identified alveolar type I
      cells to be recorded using the cell-attached configuration of the patch-clamp
      technique. CONCLUSION: This exciting new development should facilitate the
      ascription of function to alveolar type I cells and allow us to integrate this
      cell type into the general model of alveolar ion and fluid balance in health and
      disease.

PMID- 15857507
TI  - An ETP model (exclusion-tolerance-progression) for multi drug resistance.
AB  - BACKGROUND: It is known that sensitivity or resistance of tumor cells to a given
      chemotherapeutic agent is an acquired characteristic(s), depending on the
      heterogeneity of the tumor mass subjected to the treatment. The clinical success
      of a chemotherapeutic regimen depends on the ratio of sensitive to resistant cell
      populations. RESULTS: Based on findings from clinical and experimental studies, a
      unifying model is proposed to delineate the potential mechanism by which tumor
      cells progress towards multi drug resistance, resulting in failure of
      chemotherapy. CONCLUSION: It is suggested that the evolution of multi drug
      resistance is a developmentally orchestrated event. Identifying stage-specific
      time windows during this process would help to identify valid therapeutic targets
      for the effective elimination of malignancy.

PMID- 15857508
TI  - Proliferative activity of extracellular HIV-1 Tat protein in human epithelial
      cells: expression profile of pathogenetically relevant genes.
AB  - BACKGROUND: Tat is being tested as a component of HIV vaccines. Tat activity has
      been mainly investigated on cells of lymphoid/hematopoietic lineages. HIV-1,
      however, is known to infect many different cells of both solid organs and mucosal
      surfaces. The activity of two-exon (aa 1-101) and synthetic (aa 1-86) Tat was
      studied on mammary and amniotic epithelial cells cultured under low serum
      conditions. RESULTS: small concentrations of Tat (100 ng/ml) stimulated cell
      proliferation. Tat antibodies neutralized the mitogenic Tat activity. Changes of
      gene expression in Tat-treated cells were evaluated by RT-PCR and gene-array
      methods. Within 4 hours of treatment, exposure to Tat is followed by up
      regulation of some cell cycle-associated genes (transcription factors, cyclin/cdk
      complexes, genes of apoptotic pathways) and of genes relevant to HIV pathogenesis
      [chemokine receptors (CXCR4, CCR3), chemotactic cytokines (SDF-1, RANTES, SCYC1,
      SCYE1), IL6 family cytokines, inflammatory cytokines, factors of the TGF-beta
      family (TGFb, BMP-1, BMP-2)]. Up-regulation of anti-inflammatory cytokines (IL
      10, IL-19, IL-20), a hallmark of other persistent viral infections, was a
      remarkable feature of Tat-treated epithelial cell lines. CONCLUSION:
      extracellular Tat is mitogenic for mammary and amniotic epithelial cells and
      stimulates the expression of genes of pathogenetic interest in HIV infection.
      These effects may favor virus replication and may facilitate the mother-to-child
      transmission of virus.

PMID- 15857509
TI  - Rel/Nuclear factor-kappa B apoptosis pathways in human cervical cancer cells.
AB  - Cervical cancer is considered a common yet preventable cause of death in women.
      It has been estimated that about 420 women out of the 1400 women diagnosed with
      cervical cancer will die during 5 years from diagnosis. This review addresses the
      pathogenesis of cervical cancer in humans with a special emphasis on the human
      papilloma virus as a predominant cause of cervical cancer in humans. The current
      understanding of apoptosis and regulators of apoptosis as well as their
      implication in carcinogenesis will follow. A special focus will be given to the
      role of Rel/NF-kappaB family of genes in the growth and chemotherapeutic
      treatment of the malignant HeLa cervical cells emphasizing on Xrel3, a cRel
      homologue.

PMID- 15857510
TI  - Scoredist: a simple and robust protein sequence distance estimator.
AB  - BACKGROUND: Distance-based methods are popular for reconstructing evolutionary
      trees thanks to their speed and generality. A number of methods exist for
      estimating distances from sequence alignments, which often involves some sort of
      correction for multiple substitutions. The problem is to accurately estimate the
      number of true substitutions given an observed alignment. So far, the most
      accurate protein distance estimators have looked for the optimal matrix in a
      series of transition probability matrices, e.g. the Dayhoff series. The
      evolutionary distance between two aligned sequences is here estimated as the
      evolutionary distance of the optimal matrix. The optimal matrix can be found
      either by an iterative search for the Maximum Likelihood matrix, or by
      integration to find the Expected Distance. As a consequence, these methods are
      more complex to implement and computationally heavier than correction-based
      methods. Another problem is that the result may vary substantially depending on
      the evolutionary model used for the matrices. An ideal distance estimator should
      produce consistent and accurate distances independent of the evolutionary model
      used. RESULTS: We propose a correction-based protein sequence estimator called
      Scoredist. It uses a logarithmic correction of observed divergence based on the
      alignment score according to the BLOSUM62 score matrix. We evaluated Scoredist
      and a number of optimal matrix methods using three evolutionary models for both
      training and testing Dayhoff, Jones-Taylor-Thornton, and Muller-Vingron, as well
      as Whelan and Goldman solely for testing. Test alignments with known distances
      between 0.01 and 2 substitutions per position (1-200 PAM) were simulated using
      ROSE. Scoredist proved as accurate as the optimal matrix methods, yet
      substantially more robust. When trained on one model but tested on another one,
      Scoredist was nearly always more accurate. The Jukes-Cantor and Kimura correction
      methods were also tested, but were substantially less accurate. CONCLUSION: The
      Scoredist distance estimator is fast to implement and run, and combines
      robustness with accuracy. Scoredist has been incorporated into the Belvu
      alignment viewer, which is available at ftp://ftp.cgb.ki.se/pub/prog/belvu/.

PMID- 15857511
TI  - Effects of dexamethasone on TNF-alpha-induced release of cytokines from purified
      human blood eosinophils.
AB  - BACKGROUND: TNF-alpha is an important mediator in allergy also for its effects on
      eosinophils. METHODS: The effect of dexamethasone on TNF-alpha induced
      eosinophils survival, degranulation (ECP), cytokines release (IL-8, GM-CSF) and
      adhesion to VCAM-1, ICAM-1 and IgG coated wells (EPO release) were evaluated.
      RESULTS: The drug inhibited IL-8 and GM-CSF production, but not viability,
      degranulation or adhesion in human peripheral blood eosinophils. CONCLUSION:
      These results indicate that part of the activity of glucocorticosteroids on
      eosinophils may be mediated by their ability to inhibit cytokine secretion that
      in turn is important for the perpetuation of the allergic inflammation.

PMID- 15857512
TI  - Expression of Plasmodium falciparum erythrocyte membrane protein 1 in
      experimentally infected humans.
AB  - BACKGROUND: Parasites causing severe malaria in non-immune patients express a
      restricted subset of variant surface antigens (VSA), which are better recognized
      by immune sera than VSA expressed during non-severe disease in semi-immune
      individuals. The most prominent VSA are the var gene-encoded Plasmodium
      falciparum erythrocyte membrane protein 1 (PfEMP1) family, which is expressed on
      the surface of infected erythrocytes where it mediates binding to endothelial
      receptors. Thus, severe malaria may be caused by parasites expressing PfEMP1
      variants that afford parasites optimal sequestration in immunologically naive
      individuals and high effective multiplication rates. METHODS: var gene
      transcription was analysed using real time PCR and PfEMP1 expression by western
      blots as well as immune plasma recognition of parasite cultures established from
      non-immune volunteers shortly after infection with NF54 sporozoites. RESULTS: In
      cultures representing the first generation of parasites after hepatic release,
      all var genes were transcribed, but Group A var genes were transcribed at the
      lowest levels. In cultures established from second or third generation blood
      stage parasites of volunteers with high in vivo parasite multiplication rates,
      the var gene transcription pattern differed markedly from the transcription
      pattern of the cultures representing first generation parasites. This indicated
      that parasites expressing specific var genes, mainly belonging to group A and B,
      had expanded more effectively in vivo compared to parasites expressing other var
      genes. The differential expression of PfEMP1 was confirmed at the protein level
      by immunoblot analysis. In addition, serological typing showed that immune sera
      more often recognized second and third generation parasites than first generation
      parasites. CONCLUSION: In conclusion, the results presented here support the
      hypothesis that parasites causing severe malaria express a subset of PfEMP1,
      which bestows high parasite growth rates in individuals with limited pre-existing
      immunity.

PMID- 15857513
TI  - The relations between symptoms, somatic and psychiatric conditions, life
      satisfaction and perceived health. A primary care based study.
AB  - BACKGROUND: In spite of the fact that self-rated health is such an important
      factor, little is known about the aetiological background to poor perceived
      health and also less is known about the impact of life satisfaction on health in
      a primary care practice population. The aim of this study was to evaluate the
      effect of socio-demographic characteristics, lifestyle factors, symptoms, somatic
      and psychiatric conditions as well as health status measures and life
      satisfaction on perceived health in a multi-ethnic Swedish health practice
      population. METHODS: Four-hundred and seventy adult patients, who visited the
      Jordbro Health Care Centre District (JHC), Haninge Municipality, participated in
      this study. A general questionnaire with questions about socio-demographic
      characteristics, lifestyle, health status and chronic disease were used. In
      addition to that, the Primary Care Evaluation of Mental Disorders (PRIME-MD) was
      used. Furthermore, physical examinations were conducted. Unconditional logistic
      regression in successive models was used, adjusted for socio-demographic
      variables and other confounders. RESULTS: Life satisfaction is the strongest
      predictor of poor perceived health in addition to country of birth, number of
      symptoms and depression. Being born in Sweden or other Nordic countries were
      related to lower OR as compared to those born outside Europe. The OR for non
      depressed vs. depressed was 0.29 (0.17-0.48) and for non-symptomatic vs.
      symptomatic (1-3 symptoms) 0.25 (0.46-0.48). The OR and 95% CI for low
      satisfaction with life was 15.40 (5.28-44.97) in comparison to those who are
      satisfied with life. CONCLUSION: Country of birth, depression, number of symptoms
      and life satisfaction are factors related significantly and independently to
      perceived health. Life satisfaction is the strongest predictor of perceived poor
      health.

PMID- 15857514
TI  - Strain-specific differences in Neisseria gonorrhoeae associated with the phase
      variable gene repertoire.
AB  - BACKGROUND: There are several differences associated with the behaviour of the
      four main experimental Neisseria gonorrhoeae strains, FA1090, FA19, MS11, and
      F62. Although there is data concerning the gene complements of these strains, the
      reasons for the behavioural differences are currently unknown. Phase variation is
      a mechanism that occurs commonly within the Neisseria spp. and leads to switching
      of genes ON and OFF. This mechanism may provide a means for strains to express
      different combinations of genes, and differences in the strain-specific
      repertoire of phase variable genes may underlie the strain differences. RESULTS:
      By genome comparison of the four publicly available neisserial genomes a revised
      list of 64 genes was created that have the potential to be phase variable in N.
      gonorrhoeae, excluding the opa and pilC genes. Amplification and sequencing of
      the repeat-containing regions of these genes allowed determination of the
      presence of the potentially unstable repeats and the ON/OFF expression state of
      these genes. 35 of the 64 genes show differences in the composition or length of
      the repeats, of which 28 are likely to be associated with phase variation. Two
      genes were expressed differentially between strains causing disseminated
      infection and uncomplicated gonorrhoea. Further study of one of these in a range
      of clinical isolates showed this association to be due to sample size and is not
      maintained in a larger sample. CONCLUSION: The results provide us with more
      evidence as to which genes identified through comparative genomics are indeed
      phase variable. The study indicates that there are large differences between
      these four N. gonorrhoeae strains in terms of gene expression during in vitro
      growth. It does not, however, identify any clear patterns by which previously
      reported behavioural differences can be correlated with the phase variable gene
      repertoire.

PMID- 15857515
TI  - Tuberculous dilated cardiomyopathy: an under-recognized entity?
AB  - BACKGROUND: Tuberculosis (TB) is a common public health problem in many parts of
      the world. TB is generally believed to spare these four organs-heart, skeletal
      muscle, thyroid and pancreas. We describe a rare case of myocardial TB diagnosed
      on a post-mortem cardiac biopsy. CASE PRESENTATION: Patient presented with
      history suggestive of congestive heart failure. We describe the clinical
      presentation, investigations and outcome of this case, and review the literature
      on the involvement of myocardium by TB. CONCLUSION: Involvement of myocardium by
      TB is rare. However it should be suspected as a cause of congestive heart failure
      in any patient with features suggestive of TB. Increasing recognition of the
      entity and the use of endomyocardial biopsy may help us detect more cases of this
      "curable" form of cardiomyopathy.

PMID- 15857516
TI  - Diabetes (db/db) mutation-induced endometrial epithelial lipoapoptosis:
      ultrastructural and cytochemical analysis of reproductive tract atrophy.
AB  - BACKGROUND: The diabetes (db/db) mutation in C57BL/KsJ mice promotes a
      progressive cytolipidemia within the endometrial epithelial (EE) layer of the
      female reproductive tract which results in premature cellular and organ atrophy.
      The current studies focus on the ultrastructural and cytochemical changes which
      promote nuclear apoptosis and cytostructural disruption following the expression
      of endometrial hypercytolipidemia which promotes diabetes-associated
      organoinvolution and manifest infertility. METHODS: Control (normal:+/+) and
      diabetes (db/db) genotype groups were prepared for high resolution light
      microscopic analysis of cytolipidemia and nuclear apoptosis (TUNEL-labeled 3'-DNA
      fragmentation) indices and compared to the transmission electron (TEM)
      microscopic analysis of endometrial tissue samples collected from 8-16 week-old
      groups. RESULTS: Compared to controls, db/db mutation expression induced a
      dramatic increase in EE cytolipid vacuole volume and density within the
      epithelial endometrial layer. TEM analysis revealed that cytolipid vacuole
      accumulations initially aggregated at the baso-polar regions of UEE cells in
      response to the systemic hyperglycemic/hypertriglyceridemic conditions which
      characterized the (db/db) groups. Progressive cytoplasmic movement of the lipid
      pools into perinuclear compartments of affected EE cells induced nuclear
      isolation from organelles that were displaced towards peripheral cytoplasmic
      compartments. Cytochemical analysis of lipid vacuole accumulations indicated
      attraction towards, and incorporation within, the nuclear envelope of
      hyperlipidemic cells. Co-localization of nuclear apoptotic 3'-DNA fragments
      within identified hyperlipidemic EE cells was coincident with the cytochemical
      and ultrastructural identification of lipid penetration through the nuclear
      envelope in db/db mutants. CONCLUSION: These results are the first cytochemical
      indication that the metabolic disturbances in db/db mutants which promote
      hypercytolipidemia are coincident with lipoapoptosis-induced nuclear dissolution,
      as denoted by DNA fragmentation analysis. The lipidemia-induced alterations in
      intracellular organelle and nuclear architectures suggests that the metabolic
      disturbances in glucose and lipid metabolic cascades in diabetes (db/db) mutants
      disrupts cytointegrity, culminating in nuclear disregulation (as indicated by
      lipoapoptosis) and eventual premature reproductive tract organoinvolution and
      resultant, manifest, reproductive sterility.

PMID- 15857517
TI  - Sensitization and translocation of TRPV1 by insulin and IGF-I.
AB  - Insulin and insulin-like growth factors (IGFs) maintain vital neuronal functions.
      Absolute or functional deficiencies of insulin or IGF-I may contribute to
      neuronal and vascular complications associated with diabetes. Vanilloid receptor
      1 (also called TRPV1) is an ion channel that mediates inflammatory thermal
      nociception and is present on sensory neurons. Here we demonstrate that both
      insulin and IGF-I enhance TRPV1-mediated membrane currents in heterologous
      expression systems and cultured dorsal root ganglion neurons. Enhancement of
      membrane current results from both increased sensitivity of the receptor and
      translocation of TRPV1 from cytosol to plasma membrane. Receptor tyrosine kinases
      trigger a signaling cascade leading to activation of phosphatidylinositol 3
      kinase (PI(3)K) and protein kinase C (PKC)-mediated phosphorylation of TRPV1,
      which is found to be essential for the potentiation. These findings establish a
      link between the insulin family of trophic factors and vanilloid receptors.

PMID- 15857518
TI  - Reduced coronary flow reserve in Anderson-Fabry disease measured by transthoracic
      Doppler echocardiography.
AB  - Coronary flow reserve was assessed in a patient with Anderson-Fabry disease
      complicated by symmetric left ventricular hypertrophy. Coronary flow reserve was
      measurable in all three major coronary arteries providing an opportunity to
      compare regional coronary flow reserve from different vascular beds. In this
      patient all the three vascular beds supplied diffusely hypertrophied myocardium.
      Coronary flow disturbances in small intramyocardial perforating arteries were
      visible. The coronary flow reserve was reduced to a similar level (around to 2.0)
      in all three major arteries. In our patient with Anderson-Fabry disease, the
      coronary vasodilatation was blunted in a diffuse pattern corresponding to the
      myocardial hypertrophy distribution. In small intramyocardial arteries coronary
      flow was also disturbed. Accordingly, retrograde systolic flow and accelerated
      anterograde diastolic flow were documented.

PMID- 15857519
TI  - Lack of association between Chlamydia Pneumoniae serology and endothelial
      dysfunction of coronary arteries.
AB  - BACKGROUND: Recent publications brought up the hypothesis that an infection with
      Chlamydia Pneumoniae (CP) might be a major cause of coronary artery disease
      (CAD). Therefore, we investigated whether endothelial dysfunction (ED) as a
      precursor of atherosclerosis might be detectable in patients with previous
      infection with CP but without angiographic evidence of CAD. METHODS: We included
      16 patients (6 male / 10 female) of 52 consecutive patients with normal coronary
      angiography who had typical angina pectoris and pathologic findings in the stress
      test. Exclusion criteria were: active smoker, elevated cholesterol, hypertension,
      age > 65 years, diabetes mellitus, treatment with ACE-inhibitors, or known CAD.
      Blood sample analysis for serum titer against CP (aCP-IgG) was performed after
      coronary angiography. We looked for endothelial dysfunction analyzing the
      diameter of the left anterior descending coronary artery (LAD) before and after
      acetylcholine (ACh) i. c. Quantitative analysis of luminal diameter (LD) was
      performed in at least two planes during baseline conditions and after ACh for 2
      minutes in dosages of 7.2 microg/min and 36 microg/min with an infusion speed of
      2 ml/min. Using Doppler guide wire, the coronary flow velocity was measured
      continuously in the LAD. The coronary flow velocity reserve (CFVR) was measured
      after 20 microg adenosine i. c. RESULTS: 10 patients had an elevated aCP-IgG (>
      1:8). 6 patients with negative titers (aCP-IgG <or= 1:8) served as control
      (CTRL). Both groups were comparable in age, gender, angina class, results of non
      invasive stress-test and the baseline values of LD and flow. In the CP positive
      group 3 patients (30%) did not show an increase of LD after ACh as evidence of
      ED. In the CTRL group 4 patients (67 %) had ED. There was no association between
      aCP-IgG and changes of coronary blood flow after ACh. All patients showed normal
      CFVR (3.0 +/- 0.27) irrespective of their aCP-IgG values. CONCLUSION: In patients
      with typical symptoms of coronary ischemia but without angiographically visible
      CAD and absence of other factors affecting the endothelial function, a previous
      infection with CP is not associated with endothelial dysfunction.

PMID- 15857520
TI  - Nurse staffing and unplanned extubation in the pediatric intensive care unit.
AB  - OBJECTIVE: To determine the association between unplanned extubations and years
      of nurse experience and nurse-to-patient ratio in the pediatric intensive care
      unit (PICU). DESIGN: Case-control study. SETTING: University-affiliated
      children's hospital PICU. PATIENTS: Unplanned extubations were identified from
      January 1999 through December 2002. Three control patients for each of the
      patients experiencing an unplanned extubation were selected on three matching
      factors: age, intubation duration, and severity of illness as defined by the
      Pediatric Risk of Mortality (PRISM) III. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Fifty-five of 1,004 intubated patients (5.5%) experienced an
      unplanned extubation during the 4-yr period. A conditional logistic regression
      analysis was used to evaluate the association between a patient's risk of an
      unplanned extubation and the nurse's years of PICU experience and nurse-to
      patient ratio. Factors associated with unplanned extubations included the
      documentation of patient agitation (odds ratio, 2.99; 95% confidence interval,
      1.14, 7.86) and a nurse-to-patient ratio of 1:2 (one nurse caring for two
      patients) relative to a nurse-to-patient ratio of 1:1 (odds ratio, 4.24; 95%
      confidence interval, 1.00, 19.10). Years of PICU nursing experience, patient
      restraints, and the method of sedation delivery (continuous infusion vs.
      intermittent bolus) were not associated with unplanned extubations. CONCLUSIONS:
      Pediatric patients are more likely to experience an unplanned extubation when
      being cared for by a nurse assigned to two patients compared with a nurse caring
      for one patient. To provide safe patient care, health care policymakers and
      hospital administrators should consider the nurse-to-patient ratio and its
      potential association with adverse events in hospitalized children.

PMID- 15857521
TI  - Evolution of the medical practices and modes of death on pediatric intensive care
      units in southern Brazil.
AB  - OBJECTIVES: To study the possible change on mode of deaths, medical decision
      practices, and family participation on decisions for limiting life-sustaining
      treatments (L-LST) over a period of 13 yrs in three pediatric intensive care
      units (PICUs) located in southern Brazil. METHODS: A cross-sectional study based
      on a retrospective chart review (1988 and 1998) and on prospective data
      collection (from May 1999 to May 2000). SETTING: Three PICUs in Porto Alegre,
      southern Brazilian region. PATIENTS: Children who died in those PICUs during the
      years of 1988, 1998, and between May 1999 and May 2000. RESULTS: The 3 PICUs
      admitted 6,233 children during the study period with a mortality rate of 9.2%
      (575 deaths), and 509 (88.5%) medical charts were evaluated in this study. Full
      measures for life support (F-CPR) were recognized in 374 (73.5%) children before
      dying, brain death (BD) was diagnosed in 43 (8.4%), and 92 (18.1%) underwent some
      limitation of life support treatment (L-LST) There were 140 (27.5%) deaths within
      the first 24 hrs of admission and 128 of them (91.4%) received F-CPR, whereas
      just 11 (7.9%) patients underwent L-LST. The average length of stay for the death
      group submitted to F-CPR was lower (3 days) than the L-LST group (8.5 days; p <
      .05). The rate of F-CPR before death decreased significantly between 1988 (89.1%)
      and 1999/2000 (60.8%), whereas the L-LST rose in this period from 6.2% to 31.3%.
      These changes were not uniform among the three PICUs, with different rates of L
      LST (p < .05). The families were involved in the decision-making process for L
      LST in 35.9% of the cases, increasing from 12.5% in 1988 to 48.6% in 1999/2000.
      The L-LST plans were recorded in the medical charts in 76.1% of the deaths,
      increasing from 50.0% in 1988 to 95.9% in 1999/2000. CONCLUSION: We observed that
      the modes of deaths in southern Brazilian PICUs changed over the last 13 yrs,
      with an increment in L-LST. However, this change was not uniform among the
      studied PICUs and did not reach the levels described in countries of the Northern
      Hemisphere. Family participation in the L-LST decision-making process has
      increased over time, but it is still far behind what is observed in other parts
      of the world.

PMID- 15857522
TI  - Integrating the Institute of Medicine's six quality aims into pediatric critical
      care: relevance and applications.
AB  - The Institute of Medicine's report Crossing the Quality Chasm recommends "six
      aims for improvement." The aims are safety, effectiveness, equity, timeliness,
      patient-centeredness, and efficiency. This review focuses on the quality of care
      information relevant to the Institute of Medicine's six aims to assess their
      relevance, potential impact, and affect on pediatric critical care practice. It
      is concluded that if the care for pediatric intensive care patients is to be
      fundamentally improved, an understanding of the current care environment, the
      existing evidence base, the opportunities for improvement, and the documentation
      of the improvements needs to be realized. The Institute of Medicine's six aims
      provide a useful framework to advance the quality of care in this pediatric
      subspecialty and perhaps others.

PMID- 15857523
TI  - A retrospective cohort study of prognostic factors associated with outcome in
      pediatric severe sepsis: what is the role of steroids?
AB  - OBJECTIVE: Systemic corticosteroids remain controversial in the treatment of
      pediatric patients with severe sepsis. Recent studies in septic adults have shown
      decreased mortality with the use of hydrocortisone in patients with relative
      adrenal insufficiency. We conducted this large retrospective cohort study to
      further characterize severe sepsis in infants and children and correlates of
      outcome, including the use of steroids. DESIGN: Retrospective cohort study.
      SETTING: The Pediatric Health Information System (PHIS), an administrative
      database of the Child Health Corporation of America (CHCA), was queried for
      inpatients 0-17 yrs of age with severe sepsis (defined here as an International
      Classification of Disease 9th edition code for infection with use of simultaneous
      mechanical ventilation and vasoactive infusions) from 2001 to 2002. In addition
      to demographic information, use of systemic corticosteroids (hydrocortisone,
      methylprednisolone, or dexamethasone) concurrent with the ventilatory and
      vasoactive support was collected. SUBJECTS: Data from PHIS. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Patients (n = 6693) were identified at 27 PHIS
      participating CHCA member hospitals. Overall mortality was 24%; univariate
      predictors of death included use of steroids (odds ratio [OR], 1.9; 95%
      confidence interval (CI), 1.7, 2.2), older age (e.g., 13-17 yrs vs. neonates; OR,
      1.6; 95% CI, 1.3, 2.0), a hematologic-oncologic diagnosis (OR, 5.87; 95% CI,
      4.19, 8.23), and moderate vs. high case volume (OR, 1.25; 95% CI, 1.09, 1.44).
      Age, hematologic-oncologic diagnosis, case volume, and use of steroids remained
      independent predictors of mortality in multivariable analysis. CONCLUSIONS: From
      this administrative database analysis, there is no evidence that steroids are
      associated with improved outcome in critically ill infants and children with
      sepsis. Although steroids may be given preferentially to more severely ill
      children, their use was associated with increased mortality. Clinicians should
      maintain equipoise on this topic pending prospective randomized clinical trials.

PMID- 15857524
TI  - Routine enteral nutrition in neonates on extracorporeal membrane oxygenation.
AB  - OBJECTIVES: To evaluate over a 5-yr period the feasibility and tolerance of a
      protocol of routine enteral nutrition in neonates requiring extracorporeal
      membrane oxygenation (ECMO). DESIGN: Retrospective medical chart review. SETTING:
      Level III children's hospital, pediatric surgical intensive care unit. PATIENTS:
      Neonates treated with venoarterial ECMO (VA-ECMO) between January 1997 and
      January 2002. Patients with congenital diaphragmatic hernia were excluded.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Charts of all neonates
      treated with VA-ECMO were reviewed. Feasibility was evaluated by recording the
      time period needed for enteral nutrition to reach 40% of total fluid intake;
      tolerance was evaluated by reviewing data on enteral nutrition related morbidity.
      Sixty-seven of the 77 eligible patients received enteral feeding during ECMO.
      Thirty-six of these patients (54%) received 40% of total fluid intake as enteral
      nutrition within a median of 3 (range, 2-4) days. Over the years there was a
      trend toward an increasing usage of enteral nutrition from 71% to 94% (p = .07).
      Enteral nutrition was temporarily discontinued in 16 patients, with 14 showing
      gastric retentions, one showing discomfort, and one showing aspiration. Symptoms
      of bilious vomiting, blood-stained stool, or abdominal distention were not
      present. CONCLUSION: Neonates on ECMO in this series tolerated enteral feeding
      well and did not show serious adverse effects. Overall, it is our experience that
      routine use of enteral feeding in critically ill neonates on VA-ECMO is feasible.

PMID- 15857525
TI  - The strong ion gap predicts mortality in children following cardiopulmonary
      bypass surgery.
AB  - OBJECTIVE: Stewart's strong ion theory quantifies unmeasured tissue acids
      produced following hypoxia or hypoperfusion, by calculation of the strong ion
      gap. Our study objectives were as follows: a) to determine the 24-hr profile of
      the strong ion gap following cardiopulmonary bypass surgery; and b) to compare
      the prognostic value in terms of intensive care unit mortality of this variable
      with blood lactate. DESIGN: Prospective, observational study. SETTING: Tertiary
      pediatric intensive care unit. PATIENTS: Eighty-five children following surgery
      for congenital heart disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Arterial blood samples for lactate and strong ion gap calculation were obtained
      at intensive care unit admission and at 24 hrs. A raised strong ion gap (>3
      mEq/L) was present in 41.1% and 51.7% of admission and 24-hr samples,
      respectively, being elevated at both time points in 30.5%. Both the strong ion
      gap and lactate increased with surgical complexity, but neither was correlated
      with length of bypass (r = .13 and -.02) or aortic cross-clamp (r = .13 and .10).
      The crude mortality was 5.8% (5/85). Four of the five deaths were associated with
      a persistently elevated strong ion gap, in contrast to two with ongoing
      hyperlactatemia (>2 mmol/L). The admission strong ion gap (cutoff, >3.2 mEq/L)
      was superior to lactate (cutoff, >3.0 mmol/L) as a mortality predictor (area
      under receiver operating characteristic curve of 0.85 [95% confidence interval,
      0.74-0.95] vs. 0.71 [95% confidence interval, 0.44-0.98], respectively).
      CONCLUSIONS: An elevated strong ion gap occurs commonly following bypass surgery
      and appears to be superior to lactate as a mortality predictor.

PMID- 15857526
TI  - Pressure support ventilation combined with volume guarantee versus synchronized
      intermittent mandatory ventilation: a pilot crossover trial in premature infants
      in their weaning phase.
AB  - OBJECTIVE: To compare pressure support ventilation combined with volume guarantee
      (PSV-VG) to synchronized intermittent mandatory ventilation (SIMV) regarding
      safety, course of blood gases, and infant-ventilator interaction in premature
      infants. DESIGN: Prospective, two-treatment, crossover pilot study. SETTING:
      Tertiary care neonatal unit. PATIENTS: Twenty-five ventilated premature infants:
      median (range) gestational age 26.1 wks (23.1-35.7), birth weight 765 g (450
      3170), age at study 5 days (2-27), in their weaning phase. INTERVENTIONS: Infants
      were studied for three 30-min periods, starting from SIMV, followed by PSV-VG,
      and back again to SIMV. After concluding the last period, all infants were
      switched back to PSV-VG. On the next day, infants were studied in the opposite
      direction. During each period, vital parameters, ventilation parameters, degree
      of physical activity, duration of rhythmic breathing, and the number of vital
      signs monitor alarms were recorded. MEASUREMENTS AND MAIN RESULTS: Nineteen
      infants (84%) could be successfully ventilated with PSV-VG till the next day. PSV
      VG achieved a similar oxygenation level as SIMV but with significantly lower
      ventilation pressures. Comparable ventilation was achieved, but infants with
      strong respiratory drive were more liable to hyperventilation episodes during PSV
      VG. Although infants breathed more rhythmically during PSV-VG, suggesting better
      infant-ventilator synchrony, the infants' behavioral state and the fluctuations
      in blood gases did not differ. CONCLUSIONS: The potentials of PSV-VG to improve
      infant-ventilator synchrony and to decrease pressure needed to ventilate
      premature lungs are promising, even though the changes were small. However, its
      benefits during acute illness and on the final outcome remain to be proven.

PMID- 15857527
TI  - Effect of one-rescuer compression/ventilation ratios on cardiopulmonary
      resuscitation in infant, pediatric, and adult manikins.
AB  - OBJECTIVE: Optimal chest compression to ventilation ratio (C:V) for one-rescuer
      cardiopulmonary resuscitation (CPR) is not known, with current American Heart
      Association recommendations 3:1 for newborns, 5:1 for children, and 15:2 for
      adults. C:V ratios influence effectiveness of CPR, but memorizing different
      ratios is educationally cumbersome. We hypothesized that a 10:2 ratio might
      provide adequate universal application for all age arrest victims. DESIGN:
      Clinical study. SETTING: Tertiary care children's hospital. SUBJECTS: Thirty-five
      health care providers. INTERVENTIONS: Thirty-five health care providers performed
      5-min epochs of one-rescuer CPR at C:V ratios of 3:1, 5:1, 10:2, and 15:2 in
      random order on infant, pediatric, and adult manikins. Compressions were paced at
      100/min by metronome. The number of effective compressions and ventilations
      delivered per minute was recorded by a trained basic life support instructor.
      Subjective assessments of fatigue (self-report) and exertion (change in rescuer
      pulse rate compared with baseline) were assessed. Analysis was by repeated
      measures analysis of variance and paired Student's t-test. MEASUREMENTS AND MAIN
      RESULTS: Effective infant compressions per minute did not differ by C:V ratio,
      but ventilations per minute were greater at 3:1 vs. 5:1, 10:2, and 15:2 (p <
      .05). Effective pediatric compressions per minute were less at 3:1 vs. 5:1, 10:2,
      and 15:2 (p < .05) and not different between 5:1, 10:2, and 15:2 ratios.
      Effective pediatric ventilations per minute were greater at 3:1 than all other
      ratios and both 5:1 and 10:2 were >15:2 (p < .05). Effective adult compressions
      per minute were progressively greater with 3:1 vs. 5:1 vs. 10:2 vs. 15:2 (p <
      .05). Self-efficacy was assessed, and rescuers always subjectively rated 10:2 and
      15:2 ratios as easier than 5:1 or 3:1 ratios for all manikins. Rescuer pulse
      change (exertion) was greater after pediatric and adult vs. infant CPR (p < .05),
      with no significant difference by C:V ratio. CONCLUSIONS: C:V ratio and manikin
      size have a significant influence on the number of effective compressions and
      ventilations delivered during ideal, metronome-paced, one-rescuer CPR. Low ratios
      of 3:1, 5:1, and 10:2 favor ventilation, and high ratios of 15:2 favor
      compression, especially in adult manikins. Rescuers subjectively preferred C:V
      ratios of 10:2 and 15:2 over 3:1 or 5:1. Infant CPR caused less exertion and
      subjective fatigue than pediatric or adult CPR technique, without significant
      difference by C:V ratio. We speculate that a universal 10:2 C:V ratio for one
      rescuer layperson CPR is physiologically reasonable but warrants further study
      with particular attention to educational value and technique retention.

PMID- 15857528
TI  - Histologic chorioamnionitis and severity of illness in very low birth weight
      newborns.
AB  - OBJECTIVE: Estimating the risk of in-hospital mortality in the neonatal intensive
      care unit provides important information for health care providers, and several
      neonatal illness severity scores have been developed. Histologic chorioamnionitis
      (HCA) is a known cause of neonatal morbidity and mortality. To date, the
      relationship between HCA and neonatal illness severity scores has not been
      rigorously tested. In this study, the relationships among HCA, initial illness
      severity, and neonatal outcomes were analyzed in very low birth weight (VLBW)
      newborns admitted to the neonatal intensive care unit. DESIGN: Prospective.
      SETTING: Neonatal intensive care unit. PATIENTS: A total of 116 VLBW inborn
      infants (gestational age, 28.1 +/- 2.82 wks; birth weight, 1009 +/- 312 g) were
      categorized as HCA-positive (n = 67) and HCA-negative (n = 49). INTERVENTIONS:
      Placental histology was performed to identify HCA. Illness severity evaluation
      included several different neonatal illness severity scores-Clinical Risk Index
      for Babies (CRIB), CRIB-II, Score for Neonatal Acute Physiology-II (SNAP-II), and
      Score for Neonatal Acute Physiology Perinatal Extension-II (SNAPPE-II)-as well as
      the recording of severe morbidity and in-hospital mortality. MEASUREMENTS AND
      MAIN RESULTS: HCA-positive VLBW newborns showed significantly lower gestational
      age (p < .0001) and birth weight (p = .0010), together with higher CRIB, CRIB-II,
      SNAP-II, and SNAPPE-II scores at admission to the NICU (p </= .0001) and
      mortality rate (p = .0018) than HCA-negative infants. After adjustment for gender
      and gestational age in a multivariable logistic regression analysis, HCA was
      found to be an independent predictor of high illness severity: CRIB > 5 (odds
      ratio [OR], 21.37; 95% confidence interval [CI], 6.24-73.21); CRIB-II > 10 (OR,
      56.17; 95% CI, 6.75-467.2); SNAP-II > 22 (OR, 43.05; 95% CI, 11.9-155.7), and
      SNAPPE-II > 42 (OR, 48.95; 95% CI, 10.18-235.4) (all p values <.0001).
      CONCLUSIONS: Our findings indicate that HCA is a major predictor of morbidity and
      mortality in VLBW newborns.

PMID- 15857529
TI  - Recollections of Indian children after discharge from an intensive care unit.
AB  - OBJECTIVE: To analyze the recollections of children following discharge from the
      pediatric intensive care unit (PICU). DESIGN: Prospective interview-based study.
      SETTING: Multidisciplinary 111-bed general pediatric wards in a tertiary care
      hospital situated in Mumbai, India. PATIENTS: Fifty children aged between five
      and 12 yrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children's
      responses to a semistructured interview were documented between the first and
      fifth day after their transfer and interpreted by content analysis. Thirty-seven
      children (74%) had neutral recollections, nine (18%) had negative recollections,
      and eight (16%) had positive recollections of their PICU stay. Twenty-six
      children (52%) stated clean environment and 18 (36%) stated doctors as good
      features, whereas 25 (50%) stated injections as bad features of the PICU. Thirty
      two children (64%) remembered feeling scared, 37 (74%) being in pain, seven (14%)
      being thirsty, eight (16%) being hungry, and nine (18%) having disturbed sleep.
      Thirteen children (26%) appreciated the nurses and 33 (66%) the doctors for a
      good deed done by them. Fourteen children (28%) wanted changes to make the PICU
      stay comfortable. CONCLUSIONS: More toys, proactive measures to prevent
      intravenous catheter phlebitis, sedation to provide amnesia and good sleep, and
      adequate analgesia for various painful procedures are necessary for children in
      the PICU. Doctors and nurses should introduce themselves to patients and ensure
      that children are comfortable in bed and do not witness procedures being done on
      other children or a dead body.

PMID- 15857530
TI  - Extracellular hsp70 levels in children with septic shock.
AB  - OBJECTIVE: To determine whether hsp70 is elevated in the plasma of children with
      septic shock. DESIGN: Cohort study. SETTING: Two academic, tertiary pediatric
      intensive care units. PATIENTS: Ninety-four children admitted to the pediatric
      intensive care unit with septic shock and 24 control children undergoing elective
      surgical procedures. INTERVENTIONS: Venous or arterial blood sampling.
      MEASUREMENTS AND MAIN RESULTS: Children admitted to the pediatric intensive care
      unit with a diagnosis of septic shock were enrolled in the study following
      written informed consent. The control group consisted of healthy children
      undergoing elective surgical procedures. Blood samples from children in the
      septic shock or control groups were obtained within 24 hrs of admission to the
      pediatric intensive care unit or during the preoperative visit. Samples were
      collected, centrifuged, and stored at -70 degrees C. The hsp70 levels were
      measured using a commercially available enzyme-linked immunosorbent assay.
      Results were analyzed by Wilcoxon's rank sum test. Extracellular hsp70 levels in
      children with septic shock were significantly elevated compared with control
      patients (51.6 ng/mL vs. 8.1 ng/mL, respectively, p = .0004). CONCLUSIONS:
      Extracellular hsp70 levels are significantly elevated in children with septic
      shock compared with controls. Given the newly described cell signaling properties
      of hsp70, these data suggest that extracellular hsp70 may play a role in the host
      response during septic shock.

PMID- 15857531
TI  - Extubation failure in pediatric intensive care incidence and outcomes.
AB  - OBJECTIVES: To evaluate the hypotheses that children requiring reintubation are
      at an increased risk of prolonged hospitalizations, congenital heart disease, and
      death compared with age- and disease-severity-matched control patients. DESIGN:
      Prospective decision to evaluate all children undergoing extubation over a 5-yr
      time interval (1997-2001) with retrospective analysis of all failed extubation
      patients. SETTING: A large multidisciplinary, dual-site, single-system pediatric
      intensive care unit caring for critically ill and injured children. PATIENTS: All
      children intubated and ventilated during the study period (1997-2001).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Failed extubation was defined
      as the unanticipated requirement to replace an endotracheal tube within 48 hrs of
      extubation. One hundred thirty children of 3,193 pediatric intensive care unit
      patients failed extubation (4.1%). The median age of children who failed
      extubation was 6.5 months, compared with a median age of 21.3 months in the
      control population. The median age of failed extubation in children with cardiac
      disease was 9.3 months. Failed extubation patients had lengthier hospital and
      pediatric intensive care unit stays, longer duration of mechanical ventilation,
      and a higher rate of tracheostomy placement than nonfailed extubation patients (p
      < .001). Children with congenital heart disease who failed extubation had the
      longest duration of hospitalization (40.0 +/- 5.4 days). Conversely, cardiac
      patients who did not fail extubation had the shortest length of stay (11.2 +/-
      0.4 days). CONCLUSIONS: In the present trial, 4.1% of mechanically ventilated
      children failed extubation. Pediatric intensive care unit patients with failed
      extubation have longer hospital, pediatric intensive care unit, and ventilator
      courses but are not at increased risk of death relative to nonfailed extubation
      patients.

PMID- 15857532
TI  - Low postoperative hematocrit increases cerebrovascular damage after hypothermic
      circulatory arrest.
AB  - OBJECTIVE: The objective of this study was to evaluate the systemic and cerebral
      effects of different postoperative hematocrit management following
      cardiopulmonary bypass and deep hypothermic circulatory arrest. DESIGN: Animal
      case study. SETTING: Laboratory. SUBJECTS: Four-week-old Yorkshire piglets.
      INTERVENTIONS: Twelve piglets were subjected to cardiopulmonary bypass
      (hematocrit = 25%) and 100 mins of deep hypothermic circulatory arrest (15
      degrees C). After weaning cardiopulmonary bypass, they were randomized to either
      group L or H, in which the postoperative hematocrit was maintained approximately
      20% vs. approximately 30%, respectively, and survived for 6 hrs. MEASUREMENTS AND
      MAIN RESULTS: Changes in body weight, bioimpedance, and colloid oncotic pressure
      were assessed. Near-infrared spectroscopy and immunohistochemical assays for
      cerebral transforming growth factor-beta(1) and caspase-3 were performed.
      Postoperative weight gain (kg) and decreases in bioimpedance (ohms) were
      significantly less in group H (1.5 +/- 0.2 [H] vs. 2.4 +/- 0.6 [L], p = .01; 39.3
      +/- 15.5 [H] vs. 89.1 +/- 29.6 [L], p = .01). Mean colloid oncotic pressure (mm
      Hg) was significantly higher in group H (10.8 +/- 1.6 [H] vs. 8.2 +/- 0.8 [L], p
      = .01) at 6 hrs postoperatively. Oxyhemoglobin, oxidized cytochrome aa(3) (muM x
      differential path-length factor), and tissue oxygenation index (%) were
      significantly better in group H (65.7 +/- 31.8 [H] vs. -104.7 +/- 55.2 [L], p =
      .0001; 0.52 +/- 4.1 [H] vs. -12.8 +/- 6.1 [L], p = .0001, and 55.7 +/- 4.6% [H]
      vs. 45.3 +/- 6.4% [L], p = .004, respectively). Cerebral transforming growth
      factor-beta(1) and caspase-3 scores were significantly better in group H (3.0 +/-
      0.6 [H] vs. 1.9 +/- 0.9 [L], p = .04 and 1.8 +/- 0.5 [H] vs. 3.2 +/- 0.8 [L], p =
      .02, respectively). Mean arterial pressure (mm Hg) was consistently higher with
      group H (94.7 +/- 13.0 [H] vs. 78.3 +/- 11.5 [L], p = .003) despite comparable
      central venous pressure ( approximately 11 mm Hg). CONCLUSIONS: Lower
      postoperative hematocrit was associated with increased fluid retention, lower
      perfusion pressure, and worse cerebrovascular injury following deep hypothermic
      circulatory arrest. Postoperative hematocrit management may have profound
      systemic and cerebral effects after deep hypothermic circulatory arrest and
      merits further investigation.

PMID- 15857533
TI  - An opportunity: critical care beyond the intensive care unit.
AB  - INTRODUCTION: Development of formal systems of critical care follow-up is an
      essential expansion of critical care services. BACKGROUND: The impact of critical
      illness and intensive care services extends beyond the temporal and physical
      confines of critical care units. With the exception of neonatalogy, however,
      follow-up assessment and services have traditionally been provided through
      primary care or targeted subspecialist referral. As patient mortality rates
      decrease, intensivists have recognized the need to focus on alternative, patient
      centered outcomes. Models of care with collaboration between critical care and
      rehabilitation services have developed, recognizing the unique skills and
      contributions of critical care continuity. Quality of life, symptom and morbidity
      assessment, socioeconomic and family impact, satisfaction, and other variables
      have been integrated into clinical and health services research. Critical care
      follow-up, however, is not standard of care. IMPLICATIONS AND CONCLUSIONS: The
      benefit of integrating critical care services in the prehospital setting, in the
      form of triage, transport, and educational efforts, has been demonstrated.
      Establishing greater critical care follow-up is the next logical step in the care
      continuum. Intensivists should assist outpatient and intermediate care providers
      to improve patient care while simultaneously creating a crucial feedback
      mechanism for quality improvement and research efforts within intensive care.

PMID- 15857534
TI  - Central venous catheter use in the pediatric patient: mechanical and infectious
      complications.
AB  - OBJECTIVE: Following the introduction and widespread use of central venous
      catheters (CVCs) in adults, these devices are being used with increasing
      frequency in the pediatric population. This review will focus on differences
      between adults and children regarding CVC use and its potential complications.
      Both mechanical and infectious complications will be discussed. DATA SOURCES:
      Systematic review of the literature. CONCLUSIONS: CVC-related complications in
      pediatric patients are closely linked to age, body size, and age-related immune
      status. In older children, many complications are similar to those encountered in
      adult patients. Because of ongoing growth and body changes, a cutoff point beyond
      which children can be regarded as "young adults" is difficult to define; many of
      our recommendations are therefore age-related. More frequently than in adults, an
      implanted port may be the first choice in pediatric patients when long indwelling
      times are expected. The optimal site of insertion also depends on factors such as
      the patients' age as well as the need for sedation and analgesia during the
      insertion procedure. In contrast to guidelines in adult patients, we recommend
      that a radiograph always be made following CVC insertion to check the position of
      the catheter. Regarding prevention of infectious complications, we recommend full
      sterile barrier precautions during CVC insertion and strict protocols for
      catheter care. CVCs should be removed as soon as possible when they are no longer
      needed, but there is no place for elective CVC replacement on a routine basis.
      New developments such as the use of impregnated catheters might help reduce
      infection rates; however, additional research will be required to provide more
      evidence of benefit in the pediatric population.

PMID- 15857535
TI  - A critical appraisal of a systematic review: Sokol J, Jacob SE, Bohn D: Inhaled
      nitric oxide for acute hypoxemic respiratory failure in children and adults.
      Cochrane Database Syst Rev 2003 (1): CD002787.
AB  - OBJECTIVE: To review the findings and discuss the implications of the use of
      inhaled nitric oxide for acute hypoxemic respiratory failure in patients beyond
      the neonatal period. DESIGN: A critical appraisal of a systematic review.
      FINDINGS: The authors conducted a systematic review with meta-analysis to
      determine the effect of inhaled nitric oxide on clinical outcomes of patients
      with acute hypoxemic respiratory failure. The outcomes included mortality,
      changes in oxygenation, ventilator-free days, duration of intensive care and
      hospital stays, and adverse effects. It was a high-quality systematic review
      provided with strict entry criteria, an extensive literature search, and thorough
      critical appraisals. Only five trials (n = 623) met entry criteria. Inhaled
      nitric oxide had no effect on mortality in studies without crossover of treatment
      failures to open-label inhaled nitric oxide (relative risk, 0.98; 95% confidence
      interval, 0.66-1.44). A statistically significant improvement in oxygenation was
      observed in one study. The effect, however, was observed only in the first 4 days
      of treatment and was not clinically significant. The heterogeneity in study
      findings precluded meta-analyses of other clinical outcomes and adverse effects
      in the selected studies. CONCLUSIONS: There is insufficient evidence to determine
      whether inhaled nitric oxide is beneficial or harmful for acute hypoxemic
      respiratory failure in children and adults. While awaiting further studies to
      prove its benefit, inhaled nitric oxide should not either be recommended as a
      standard management or excluded for the treatment of acute hypoxemic respiratory
      failure.

PMID- 15857536
TI  - Reproducibility of cerebral oxygenation measurement in neonates and infants in
      the clinical setting using the NIRO 300 oximeter.
AB  - OBJECTIVE: To study reproducibility of cerebral tissue oxygenation index (cTOI)
      values in neonates and infants in a clinical setting using the NIRO 300 oximeter
      (Hamamatsu Photonics, Hamamatsu City, Japan). DESIGN: Clinical, observational
      study. SETTING: University hospital, pediatric intensive care unit. PATIENTS:
      Twenty neonatal and pediatric intensive care patients (age 0-190 days; median 4.5
      days). INTERVENTIONS: Reproducibility of cTOI was measured at the lateral
      forehead of the patients. MEASUREMENTS AND MAIN RESULTS: Sensor exchange
      experiments were performed by removing the sensor and reapplying another sensor
      (sensor 1 vs. sensor 2) at the same position. Simultaneous measurements,
      comparing cTOI values from the right and left forehead, were performed using both
      sensors. Corresponding sensor exchange experiments were performed within 10 mins.
      All tests were done under stable, steady-state cardiorespiratory conditions. Data
      were compared using Bland-Altman bias analysis and paired, two-sided Student's t
      test (p < .05). Sensor exchange experiments and simultaneous left-to-right
      forehead measurements revealed only small mean differences (<5%) and no
      significant differences between corresponding values (p = .953/.164). However,
      Bland-Altman bias analysis revealed poor agreement with large 95% limits of
      agreement in particular for sensor exchange experiments (-17.8% to 17.6%) and
      less for simultaneous left and right measurements (-14.4% to 10.4%). CONCLUSIONS:
      The present study shows that cTOI measurements using the NIRO 300 oximeter at the
      lateral forehead of neonates and infants are not well reproducible under clinical
      conditions. This raises the question whether generally valid normal values can be
      defined with the used approach and makes it difficult to determine a normal range
      of cerebral oxygenation.

PMID- 15857537
TI  - Use of recombinant factor VIIa for refractory hemorrhage during extracorporeal
      membrane oxygenation.
AB  - OBJECTIVE: To describe the outcome and treatment of two patients with recombinant
      factor VIIa (rFVIIa) for severe hemorrhage associated with extracorporeal
      membrane oxygenation (ECMO). DESIGN: Case report. SETTING: A 38-bed pediatric
      intensive care unit and 20-bed pediatric cardiac intensive care unit at a
      tertiary care children's hospital. PATIENT: Two patients with life-threatening
      hemorrhagic complications associated with ECMO requiring massive transfusion of
      blood products. INTERVENTIONS: Administration of repeated doses of rFVIIa at 90
      microg/kg/dose. MEASUREMENT AND MAIN RESULTS: PATIENT 1 was an 11-yr-old male
      with a dilated cardiomyopathy who had undergone an orthotopic heart transplant
      treated with venoarterial ECMO postoperatively for right ventricular dysfunction.
      PATIENT 2 was a 13-yr-old male treated with venoarterial ECMO for cardiopulmonary
      failure from necrotizing staphylococcal pneumonia. Both patients had severe
      hemorrhage from the cannulation sites and thoracostomy tubes requiring massive
      transfusion to maintain intravascular blood volume and replace clotting factors.
      Both patients were treated with rFVIIa every 2-4 hrs and attained hemostasis.
      PATIENT 1 was administered three doses and PATIENT 2 was administered ten doses.
      No evidence of abnormal thrombus formation was noted in their respective ECMO
      circuits. CONCLUSIONS: The efficacy of rFVIIa in reducing intractable bleeding
      postcardiac surgery and in other coagulopathic states is being investigated.
      Despite theoretical concerns of thrombosis, these cases illustrate that there may
      be a role for the cautious use of rFVIIa in treating severe and intractable
      hemorrhage associated with ECMO.

PMID- 15857538
TI  - The use of recombinant factor VIIa in a patient with Noonan syndrome and life
      threatening bleeding.
AB  - OBJECTIVE: To present a case report of a patient with Noonan syndrome who
      developed life-threatening gastrointestinal bleeding shortly after cardiac
      surgery that was successfully treated with recombinant factor VIIa. DESIGN: Case
      report. SETTING: Pediatric intensive care unit of a children's hospital. PATIENT:
      Ten-month-old with Noonan syndrome and massive gastrointestinal bleeding
      resulting in severe hypovolemic shock. INTERVENTIONS: Recombinant factor VIIa was
      used in this patient's severe bleeding associated with Noonan syndrome after no
      other supportive measures were successful. MEASUREMENTS AND MAIN RESULTS:
      Recombinant Factor VIIa significantly decreased the patient's bleeding and
      allowed his hypovolemic shock to improve. Ultimately, the patient made a complete
      recovery. CONCLUSIONS: Noonan syndrome has a constellation of both cardiac and
      noncardiac malformations including an increased risk of bleeding, and recombinant
      factor VIIa is an important agent in the treatment of significant bleeding.

PMID- 15857539
TI  - Posttraumatic cholothorax in a child: case report and review of the literature.
AB  - OBJECTIVE: Thoracobiliary fistula, subsequent to a combined thoracic and hepatic
      blunt trauma, is a rare complication, which calls for a high index of suspicion
      during diagnostic workup. Due to its uncommon nature, especially in children, and
      hence the paucity of reports in literature, no consensus has been reached on its
      optimal management. PATIENTS AND METHODS: We report on a 4-yr-old girl, who
      developed a cholothorax after a blunt thoracoabdominal trauma. She was
      successfully treated through conservative management with drainage, antibiotics,
      and a low-fat diet. The cases previously described in the English literature are
      reviewed, and management is discussed. CONCLUSION: The recent tendency to observe
      rather than explore abdominal trauma and the absence of a definitive diagnostic
      test for diaphragmatic injury may contribute to a delayed diagnosis of the
      components that may result in the development of a fistula. Literature review
      substantiates endoscopic retrograde cholangiopancreatography as the imaging
      modality of choice, because it has the potential of therapeutic intervention by
      sphincterotomy or stent placement. A nonoperative approach was successful in this
      case.

PMID- 15857540
TI  - Hypertensive emergency associated with thoracoabdominal aneurysm: case report and
      review.
AB  - OBJECTIVE: To provide a description and thorough discussion of the diagnostic
      considerations for a rare case of malignant hypertension and aortic aneurysm in a
      pediatric patient. DESIGN: Case report. SETTING: A university pediatric intensive
      care unit. SUBJECT: A young child with a hypertensive crisis and a
      thoracoabdominal false aortic aneurysm. INTERVENTIONS: The child required urgent
      surgical intervention to resect the aneurysm and aggressive medical therapy in
      the pediatric intensive care unit to treat the underlying hypertension.
      CONCLUSIONS: Hypertensive emergencies and aortic aneurysms are unusual but
      potentially lethal entities in pediatric patients, requiring a high index of
      suspicion, prompt initiation of medical therapy, and urgent surgical
      consultation.

PMID- 15857541
TI  - Ceftriaxone-induced hemolytic anemia and hepatitis in an adolescent with
      hemoglobin SC disease.
AB  - OBJECTIVES: To describe a case of a ceftriaxone-induced hemolytic anemia and
      hepatitis leading to multiple organ failure and death in an adolescent with
      hemoglobin SC disease and to review the previous cases of this rare and
      potentially fatal disorder in children. DESIGN: Case report and literature
      review. SETTING: Intensive care unit. PATIENT: Adolescent with hemoglobin SC.
      INTERVENTIONS: Emergency treatment. MEASUREMENTS AND MAIN RESULTS: After 4 days
      of ceftriaxone therapy, the adolescent experienced an acute hemolytic reaction
      (hemoglobin decreased to 5 g/dL with hemoglobinuria) and severe hepatitis (all
      enzymes increasing dramatically including aminoaspartate transferase >20,000
      IU/L). Renal failure and ultimately multiple organ failure ensued, and the
      patient died on hospital day 19. Direct antiglobulin tests on red cells obtained
      from the patient on hospital day 2 showed microscopic agglutination with
      polyspecific and anticomplement (C3) antiglobulin reagents. Plasma samples showed
      macroscopic agglutination reactions when incubated in the presence of
      ceftriaxone, many days after cessation of ceftriaxone, indicating the continued
      presence of ceftriaxone-dependent antibodies. CONCLUSIONS: Drug reactions leading
      to hemolysis are relatively uncommon, and a total of ten cases of ceftriaxone
      induced hemolytic anemia have been reported in children. The present case
      describes an adolescent who ultimately died on hospital day 19 from multiple
      organ failure, although the presentation of this case seems atypical in several
      respects. Children with clinical syndromes that place them at risk for hemolysis
      and children who frequently require broad spectrum antibiotics present unique
      diagnostic challenges, and the possibility that hemolytic syndromes may be due to
      ceftriaxone must be considered.

PMID- 15857542
TI  - Pediatric trauma susceptibility to sepsis.
AB  - OBJECTIVE: The purpose of this review is to review how pediatric trauma may
      predispose children to sepsis. DESIGN: The information discussed in this report
      is derived from a recent literature review of pediatric trauma and related topics
      and discussion at an international consensus conference on pediatric sepsis.
      MEASUREMENTS AND MAIN RESULTS: There is a paucity of evidence on sepsis-related
      complications in pediatric trauma patients. Severe traumatic brain injury is a
      leading predisposing factor for sepsis complications. Excluding burn trauma,
      traumatically injured children without severe head injury rarely succumb to
      overwhelming sepsis. CONCLUSIONS: Patients with multiple traumatic injuries are
      frequently admitted to the intensive care unit, and because head injury is the
      most common ailment, unconscious patients with a combination of injuries that
      include head injury will regularly require mechanical ventilation and central
      venous access and are at risk for life-threatening nosocomial infections. Outside
      of pulmonary contusions, organ-specific causes of infection are infrequent.

PMID- 15857543
TI  - Sepsis in pediatric burn patients.
AB  - OBJECTIVE: To review the specific infections common in pediatric burns, including
      their categorization, diagnosis, and treatment. DESIGN: Review of the literature
      and expert opinion. RESULTS: Children with serious burns are prone to a host of
      septic complications. This proclivity to infection is secondary to the
      immunosuppressive effect of burn injury, the loss of the skin and mucosal
      physical barriers, and the requirement for invasive support devices. CONCLUSION:
      Sepsis is common in the pediatric burn patient and can markedly increase
      morbidity and mortality. Anticipation, prompt diagnosis of infection, and
      effective therapy can result in successful outcomes for many of these children.

PMID- 15857544
TI  - Physicians' ability to diagnose sepsis in newborns and critically ill children.
AB  - OBJECTIVE: To elucidate physicians' ability to correctly diagnose infection in
      critically ill children in three different situations: 1) post hoc adjudication
      (e.g., ward rounds, outcome determination in surveillance studies or controlled
      trials), 2) when decisions must be made (e.g., sepsis workup in suspected
      infection), c) and applying suggested adult consensus conference definitions in
      children. METHOD: Appraisal of two previously published studies and a data
      simulation model. SETTING: Data of the reviewed studies were obtained from a
      multidisciplinary neonatal and a pediatric intensive care unit in tertiary
      hospitals. INTERVENTIONS: None. MAIN RESULTS: In the first study reviewed, the
      post hoc adjudication of 167 consecutive cases of suspected infection was carried
      out by a fifth-year medical student and three senior consultants. The agreement
      of the three experts beyond chance in the 119 episodes not classifiable
      unanimously by a priori defined criteria into proven sepsis or no infection was
      poor. In the second study reviewed, the physicians provided daily predictions of
      the likelihood of infection (pretest probability) in premature infants and
      critically ill children (2567 hospitalization days). Estimated pretest
      probabilities provided at the time of sepsis workup showed a remarkable
      predictive accuracy (area under the receiver operating characteristic curve,
      0.85). In the simulation model, in which catheter-related sepsis was assumed,
      correct classification of patients from a central and a peripheral culture
      decreased to 56% when a sensitivity of 70%-80% was assumed for blood cultures and
      amounted to 15% only when a sensitivity of 30%-50% was imputed. CONCLUSION:
      Misclassification is a serious threat in post hoc adjudication of episodes or
      when consensus definitions rely on the application of criteria with imperfect
      sensitivity (e.g., the positivity of blood cultures in premature infants or
      children). This underscores the need to use probability-based categorizations
      such as probable and possible infection.

PMID- 15857545
TI  - Severity of illness and organ dysfunction scoring in children.
AB  - OBJECTIVE: To describe predictive and descriptive general scores that can be used
      to estimate the severity of illness in critically ill children. DESIGN: Review of
      the medical literature. SETTING: Pediatric intensive care units (PICUs).
      PATIENTS: Critically ill children. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Two predictive scores are frequently used in PICUs: the Pediatric Risk
      of Mortality III score and the Pediatric Index of Mortality 2. The data
      considered in these scores are collected at baseline. Predictive scores can be
      used to compare expected and observed mortality in PICUs or to estimate the
      balance in the baseline severity of illness of patients included in the different
      arms of a randomized clinical trial. Only one descriptive score is validated to
      estimate the severity of cases of multiple organ dysfunction syndrome in PICUs,
      namely, the Pediatric Logistic Organ Dysfunction score. The data required to
      calculate this score are collected from baseline to discharge from the PICU or up
      to 2 hrs before death in the PICU. The Pediatric Logistic Organ Dysfunction score
      can be used to describe the clinical outcome of patients during their stay in a
      PICU. CONCLUSION: Pediatric Risk of Mortality III, Pediatric Index of Mortality
      2, and Pediatric Logistic Organ Dysfunction scores are the best available tools
      to estimate the severity of illness in critically ill children.

PMID- 15857546
TI  - What is the role of neonatal organ dysfunction and illness severity scores in
      therapeutic studies in sepsis?
AB  - The goal of therapeutic studies in neonatal sepsis is to increase disability-free
      survival. Mortality may not be an adequate measure of outcome if it is reduced at
      the cost of increased disability. No neonatal organ dysfunction score has yet
      been validated as a reliable surrogate for disability-free survival. To validate
      a score as a surrogate would require randomized trials showing 1) a causal
      connection between change in the score and change in disability-free survival and
      2) that the score fully captured all the effects of treatment on disability-free
      survival. Neonatal illness severity scores provide a convenient, but imperfect,
      tool to adjust for risk of sepsis in observational studies. They can help to
      stratify infants by risk of sepsis at entry to trials, allowing analyses of
      outcome in predefined subgroups. However, they cannot circumvent the need for
      randomized trials of adequate size in neonatal sepsis, which address disability
      free survival as the primary outcome.

PMID- 15857547
TI  - What have we learned from observational studies on neonatal sepsis?
AB  - OBJECTIVE: To assess how observational studies on neonatal sepsis can help define
      the knowledge base required for neonatal randomized, clinical trials. DESIGN:
      Methodologic review of past observational studies and critical reviews. RESULTS:
      Observational studies on neonatal sepsis have suffered from important
      limitations: failure to employ multivariate analyses, considering infection in
      isolation (ignoring coexisting respiratory distress), failure to provide
      likelihood ratios for predictors and combinations of predictors, and ignoring the
      phenomenologic dimension of clinicians' experience. CONCLUSION: Future
      observational studies must address three key issues. They should begin with a
      clear analytic and sampling plan that pays careful attention to the proper use
      and reporting of multivariate analyses. Second, they must explicitly address two
      subpopulations: critically ill newborns with negative cultures and asymptomatic
      newborns with positive cultures. Finally, they should be theory driven and
      provide empirical physiologic data that permit situating their results in the
      context of the evolving systemic inflammatory response syndrome and PIRO
      (predisposition, infection, host response, organ dysfunction) models.

PMID- 15857548
TI  - Defining bacterial meningitis and other infections of the central nervous system.
AB  - OBJECTIVE: To define central nervous system infections of infants and children
      that occur as co-morbid or predisposing conditions of sepsis. DESIGN: Standard
      pediatric infectious disease references and the pertinent literature in English
      were reviewed from 1960 to 2002 to ascertain the previous methods and definitions
      utilized in clinical studies of the epidemiology and treatment of bacterial
      infections of the central nervous system. An accepted definition of bacterial
      meningitis defined by the Infectious Disease Society of America was reviewed and
      adapted to the previous clinical definitions. The information was formulated into
      a proposed standard for definite, probable, and possible bacterial infections of
      the central nervous system. RESULTS: The diagnosis of definite bacterial
      infection of the central nervous system, including bacterial meningitis, requires
      the isolation of the pathogen from the cerebrospinal fluid or other significant
      clinical site such as surgical tissue, an implanted device, or blood. Probable
      bacterial infection is defined by the association of a compatible clinical
      syndrome or cerebrospinal fluid changes associated with bacterial meningitis or
      other central nervous system infection, and confirmed as an anatomically defined
      infection by imaging or surgery, in association with positive blood cultures or
      bacterial antigen from cerebrospinal fluid. Possible bacterial meningitis may be
      defined as a compatible clinical syndrome with predefined cerebrospinal fluid
      changes in the absence of a confirmatory culture or antigen test from any site.
      CONCLUSIONS: Bacterial meningitis and other central nervous system bacterial
      infections can be defined as definite, probable, and possible with a combination
      of a defining compatible clinical syndrome and an anatomic definition by surgery
      or imaging, coupled with isolation of the organism, bacterial antigen, or other
      defining molecular component of the organism.

PMID- 15857549
TI  - What have we learned about randomized, controlled trials in neonatal sepsis?
AB  - OBJECTIVE: To identify strategies to enable randomized, controlled trials in
      neonatal sepsis to recognize therapies that increase disability-free survival.
      METHODS: Rapid literature review. RESULTS: Randomized, controlled trials are the
      gold standard for testing a therapy because they minimize bias. However,
      randomized, controlled trials must also minimize random error if they are to
      detect moderate (and realistic) improvements in rates of disability-free survival
      reliably. This requires surprisingly large samples (i.e., thousands rather than
      hundreds). Against this perspective, most neonatal trials have been too small to
      be conclusive, so most neonatal therapies remain incompletely evaluated. As in
      specialties like cardiology and obstetrics, achieving reliable trials in neonatal
      sepsis will require international collaboration, simpler data sets, more cost
      effective recruitment strategies, less exclusive criteria for selecting
      collaborators and patients, and an appreciation by clinicians and data-monitoring
      committees that substantially greater sample sizes are needed to limit the play
      of chance. Prospective meta-analysis using individual patient data is a promising
      strategy. It requires researchers to obtain funding from their national agencies
      to conduct similar trials according to an agreed protocol with prespecified
      hypotheses, interventions, power calculations, data sets, and measures of
      outcome. Prospective meta-analysis combines the methodologic advantages of a
      single "megatrial" with the practical advantages that financial burdens are
      spread internationally and different national funding cycles can be more flexibly
      accommodated. CONCLUSIONS: Prospective meta-analysis using individual patient
      data is a promising strategy for achieving large-scale, randomized evidence in
      neonatal sepsis.

PMID- 15857550
TI  - Alternative outcome measures for pediatric clinical sepsis trials.
AB  - OBJECTIVE: To review nonmortality outcome measures in clinical trials of
      therapies to treat sepsis in children. DATA SOURCE: Literature review using the
      search word terms "sepsis" + "surrogate markers," "sepsis" + "biomarkers," or
      "sepsis" + "outcomes." STUDY SELECTION: Articles were generally categorized as
      those dealing with review of patient-centered outcomes, characteristics of good
      surrogate markers, resolution of organ dysfunction, morbidity and functional
      status, quality-of-life measures, intensive care unit costs, and biomarkers. DATA
      EXTRACTION AND SYNTHESIS: Information potentially relevant for development of
      surrogate markers for pediatric sepsis trials was extracted and organized as
      noted above. CONCLUSIONS: Multiple potential surrogate markers are being actively
      investigated for their potential validity and utility in pediatric clinical
      trials of sepsis and increasingly for adult sepsis trials. This is important
      because as mortality decreases, it becomes an impractical primary end point.
      Surrogate end points that address patient-related morbidity and intensive care
      unit costs may also be quantified. Treatment of sepsis and corresponding end
      points for clinical trials should be aimed at both the duration and the quality
      of survival.

PMID- 15857551
TI  - Reducing the global burden of sepsis in infants and children: a clinical practice
      research agenda.
AB  - OBJECTIVE: Sepsis remains a predominant cause of mortality and morbidity in
      children in the developing and industrialized world. This review discusses a
      clinical practice research agenda to reduce this global burden. DESIGN: Summary
      of the literature with analysis by experts. RESULTS: Many interventions have been
      proven effective in decreasing sepsis. Heterologous immunization with attenuated
      Bacillus Camille Guerin vaccine reduces all-cause mortality, and specific
      immunizations further reduce morbidity and mortality from many specific microbes.
      Antepartum antibiotics reduce the prevalence of cerebral palsy and mortality in
      infants. Administration of antibiotics to neonates with signs of sepsis reduces
      all-cause mortality five-fold and can also reduce mortality in the big four
      killers of children: severe pneumonia, diarrhea, malaria, or measles.
      Immunonutrition with zinc and vitamin A can further reduce morbidity in diarrhea
      and pneumonia and reduce mortality in measles. First-hour rapid intravenous fluid
      resuscitation achieves 100% survival in dengue shock, and time-sensitive fluid
      resuscitation and inotropic support reduces mortality ten-fold in meningococcal
      septic shock. Multiple organ failure occurs when late or inadequate resuscitation
      results in systemic thrombosis or when infection is not eradicated because of
      immunosuppression or inadequate source control. CONCLUSIONS: The global burden of
      sepsis can be reduced by 1) prevention with improved heterologous or specific
      vaccines and vitamin or mineral supplement programs; 2) early recognition and
      treatment with appropriate antibiotics, intravenous fluid resuscitation, and
      inotropic support in organized healthcare-delivery systems; and 3) development of
      new diagnostics and therapeutics that reduce systemic thrombosis, improve immune
      function, and kill resistant organisms.

PMID- 15857552
TI  - Identification of central venous catheter-related infections in infants and
      children.
AB  - OBJECTIVE: To define central venous catheter-related infections in infants and
      children for the purpose of enrolling children in sepsis studies, for
      epidemiology and surveillance studies, and for clinical management. METHODS:
      Review of the literature and consensus of experts. RESULTS: No changes were made
      to the current Centers for Disease Control and Prevention criteria for defining
      local catheter infection. Because catheter tips are not available as often in
      children as in adults, smaller blood volumes are drawn per culture decreasing
      sensitivity, and antibiotics are rarely withheld, slight modifications to the
      existing adult Centers for Disease Control and Prevention criteria were made to
      increase practical use. Catheter-related bloodstream infection was categorized as
      definite, probable, and possible based on culture results and clinical symptoms.
      CONCLUSIONS: For the purposes of enrolling patients with sepsis in clinical
      trials, only patients who meet criteria for definite catheter-related bloodstream
      infection should be categorized as having the catheter as the infection source.
      Because many patients suspected of having catheter-related bloodstream infection
      do not have positive blood culture results, which makes the confirmation of
      infection difficult, we recommend that these patients not be enrolled in sepsis
      trials. Because catheter tips are often not obtained for culture in children, the
      epidemiology of catheter-associated bloodstream infection (bloodstream infection
      in a patient who has a central venous catheter and no other obvious source of
      infection) is better understood than the epidemiology of confirmed catheter
      related bloodstream infection in infants and children. Definitions for catheter
      related bloodstream infection that compare the through-catheter and peripheral
      culture for time to positivity or for quantitative growth are unlikely to be
      falsely positive, but sensitivity requires further validation.

PMID- 15857553
TI  - Defining urinary tract infection in the critically ill child.
AB  - OBJECTIVE: To define urinary tract infections in critically ill children in the
      intensive care unit setting for the purpose of surveillance of infection,
      enrollment of children in sepsis trials, and for trials of therapy and
      prevention. DESIGN: Summary of the literature with review and consensus by
      experts in the field. RESULTS: A variety of definitions, only some of which have
      been validated for use in children, were identified. The Centers for Disease
      Control criteria for the definition of nosocomial infection have been used to
      establish surveillance data for inter-institutional comparison. Validated
      definitions for the febrile child were identified. Using the known
      characteristics of symptoms, signs, and laboratory criteria for urinary tract
      infections, definitions for definite, possible, and probable urinary tract
      infection were derived. CONCLUSIONS: Definitions for definite, probable, and
      possible urinary tract infection were achieved by consensus that can be used for
      surveillance and enrolment in sepsis trials. Future research should determine the
      utility of these definitions in the critically ill child and adapt them
      accordingly.

PMID- 15857554
TI  - Scope and epidemiology of pediatric sepsis.
AB  - OBJECTIVE: To summarize the scope and epidemiology of pediatric sepsis. DESIGN:
      Review of published literature. RESULTS: Sepsis is a leading cause of death in
      infants and children, with >42,000 cases of severe sepsis annually in the United
      States and millions worldwide. Half of the children with severe sepsis in the
      United States are infants, and half of infants are low- or very low-birth-weight
      babies. Underlying disease occurs in 49% of U.S. children with severe sepsis.
      National hospital costs associated with severe sepsis in the United States were
      $2.3 billion in 1999. Relatively simple strategies to identify and treat children
      with sepsis in the developing world have shown remarkable success. These
      strategies have included empirical antibiotics in babies at high risk of sepsis
      and aggressive fluid resuscitation in Dengue hemorrhagic fever. CONCLUSIONS:
      Sepsis is a major health problem among children in both developing and
      industrialized countries. However, sepsis is both preventable and treatable.
      Improved prevention and treatment of sepsis could have a substantial effect on
      survival and quality of life of all children, both those who are otherwise
      healthy and those who are chronically ill. The variations in the epidemiology of
      pediatric sepsis underscore the need for a multidisciplinary approach and
      consistently applied definitions.

PMID- 15857555
TI  - Intraabdominal infections in infants and children: descriptions and definitions.
AB  - OBJECTIVE: To define intraabdominal infections in infants and children. DESIGN:
      Summary of the literature with review and consensus by experts in the field.
      RESULTS: Intraabdominal infections are common in infants and children and
      comprise a broad range of disorders of greatly variable severity. In addition to
      microbiologically mediated processes, other inflammatory disorders frequently
      present similar clinical syndromes. More aggressive and effective therapy for
      prematurity, chronic diseases of childhood, malignancies, immunodeficiencies, and
      organ failure, including transplantation, is likely to increase the frequency
      with which some of these infections are encountered. Only a limited number of
      processes have been clearly defined in the pediatric literature. CONCLUSIONS:
      Criteria defining intraabdominal infection are proposed based on reports in the
      pediatric literature and expert opinion. Additional study of individual
      disorders, diagnostic criteria, and approach to management is warranted.

PMID- 15857556
TI  - Pediatric surgical site and soft tissue infections.
AB  - OBJECTIVE: The purpose of this review is to provide background and a concise set
      of definitions for pediatric surgical site and wound infections. DESIGN: The
      information discussed in this report is derived from a literature review and
      discussion at an international consensus conference on pediatric sepsis.
      MEASUREMENTS AND MAIN RESULTS: There is a paucity of literature on pediatric
      surgical site and wound infection definitions. Excluding burn wounds, surgical
      site and wound infections rarely lead to overwhelming sepsis. Nevertheless,
      surgical site or wound infections including pressure ulcers can lead to
      significant morbidity in the pediatric critical care setting. CONCLUSIONS:
      Although surgical site and wound infections rarely lead to intensive care unit
      admissions, definitions are still valuable for stratifying potential candidates
      for sepsis trials.

PMID- 15857557
TI  - Bloodstream infection in children.
AB  - OBJECTIVE: To establish the definitions of bloodstream infection (BSI) in
      children for the purposes of identifying BSI for early therapy, enrollment in
      sepsis trials, and epidemiology and surveillance studies. METHODS: Generalized
      medical literature search using various combinations of the terms "bloodstream
      infection," "children," and "sepsis." RESULTS: The medical literature is sparse
      on these topics; therefore, these recommendations are adapted from guidelines
      designed for adults. BSI overlaps with other areas of sepsis, such as catheter
      related BSI, which will be covered separately. This discussion focuses on BSI of
      unknown origin, also known as primary BSI. CONCLUSION: A BSI is the presence of a
      pathogen in the blood. Its clinical significance should be determined by the
      presence of the host response as defined by the modified criteria for systemic
      inflammatory response syndrome SIRS in children or a clinically recognizable
      syndrome. Definitions of BSI for the purposes of sepsis trials may differ from
      those for epidemiologic or surveillance studies.

PMID- 15857558
TI  - Definitions of bloodstream infection in the newborn.
AB  - OBJECTIVE: To develop definitions of bloodstream infections in the newborn that
      would enable clinicians to identify infection early, so patients can be enrolled
      in clinical trials. The definitions should be useful for surveillance and
      epidemiologic purposes. METHOD: Search of EMBASE, MEDLINE, and Cochrane Library
      using age and English language limited key words sepsis, septicemia, and shock.
      Extensive study of textbook of neonatology and discussions with experts in the
      field. RESULTS: The search identified >2,000 references. The most appropriate
      were selected and reviewed. Definitions of bloodstream infection were developed
      after consultation with an international faculty. CONCLUSION: Current definitions
      of neonatal infection (and associated categories) used by neonatal clinicians and
      researchers have been either adapted/modified from definitions developed for
      adults or generated by individuals to suit their local needs or the needs of a
      particular study. It is clear that definitions generated for adults are not
      applicable to children or to newborn infants. In addition, developing and using
      unique definitions to suit individual or local needs make comparisons of outcome
      data and result of studies very difficult. This article proposes a set of
      definitions that are based as much as possible on current evidence. These
      definitions may be applicable widely for daily management of an infant with an
      infection and for research and epidemiologic studies.

PMID- 15857559
TI  - Diagnosing meningococcemia as a cause of sepsis.
AB  - OBJECTIVE: In 2004, a consensus meeting of critical care and infectious disease
      experts was organized to review and make recommendations on current definitions
      of infections, sepsis, and organ failure for neonates and children and for the
      predisposing conditions leading to these diseases. Among the infections leading
      to sepsis, meningococcemia is so distinguishable that a separate article on its
      diagnosis and management was thought to be warranted. DESIGN AND METHODS: The
      process included a modified Delphi method, a consensus conference, subsequent
      smaller meetings of subgroups and key individuals, and electronic-based
      discussion among subgroups. A systematic review of the literature was undertaken.
      CONCLUSIONS: Early recognition and treatment of likely meningococcal sepsis has
      led to decreased mortality. Since the start of vaccination against serogroup C,
      the prevalence of this disease has decreased. Not only the possible presence of a
      meningococcal sepsis is important, but also the assessment of the shock state and
      the severity of disease and the possible presence of meningoencephalitis. There
      are also a number of genetic predispositions determining the severity of disease.
      The only three randomized trials in this disease have led to the conclusion that
      mortality is not a stable end point. Improvement in organ function, morbidity
      (including amputations), and functional outcome are better outcome measures.

PMID- 15857560
TI  - Concept of PIRO as a new conceptual framework to understand sepsis.
AB  - OBJECTIVE: To define and introduce the PIRO model for categorizing sepsis in
      infants and children. DESIGN: A summary of the literature published during the 5
      yrs since this concept has been formulated, along with a consensus opinion of
      experts in the field of sepsis and septic shock. RESULTS: The imprecision and
      intrinsic heterogeneity of the patient population defined as septic has prompted
      the introduction of a new sepsis classification system known as PIRO. PIRO stands
      for predisposition, infection, response, and organ dysfunction. It is hoped that
      by defining the septic process through a detailed analysis of each of its
      component parts, the development of sepsis will be better understood. This may
      contribute to improved therapeutic interventions for sepsis in the future.
      CONCLUSIONS: The PIRO model is a conceptual framework for understanding sepsis
      that has many favorable attributes. The PIRO model should be directly tested in
      both the research laboratory and in clinical trial designs to determine the
      practical value and clinical relevance of this new classification scheme for
      sepsis.

PMID- 15857561
TI  - Pediatric sepsis definitions: past, present, and future.
AB  - OBJECTIVE: To review the past, present, and future definitions of sepsis and the
      systemic inflammatory response syndrome in children. METHODS: Review of the
      literature. RESULTS: The history and development of the adult-derived sepsis
      syndrome and its application to pediatric-specific sepsis definitions is
      provided. Initially, only adult definitions were applied to pediatric studies.
      Recently, pediatric-specific definitions have been published. The pediatric
      consensus conference-derived definitions for systemic inflammatory response
      syndrome, sepsis, severe sepsis, and septic shock are summarized, and their
      limitations are discussed. CONCLUSIONS: The potential value and inconsistencies
      of the current pediatric-specific sepsis definitions are discussed. Future
      direction of the definitions and their applications are presented.

PMID- 15857562
TI  - Genetic polymorphisms in sepsis.
AB  - CONTEXT: Wide variability exists in the susceptibility to and outcome from sepsis
      even within similar intensive care unit populations. Some of this variability in
      the host may be due to genetic variation in genes coding for components of the
      innate immune response. OBJECTIVE: To review the evidence for a genetic influence
      on the susceptibility to and outcome from sepsis. DESIGN: Literature review.
      PATIENTS: Variety of adult and pediatric patients with various critical illnesses
      and infections. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Susceptibility to
      clinical symptoms of sepsis and outcome as measured by severity of disease and
      mortality. RESULTS: Polymorphisms in genes coding for proteins involved in the
      recognition of bacterial pathogens (Toll-like receptor 4, CD14, Fc(gamma)RIIa,
      and mannose-binding lectin) and the response to bacterial pathogens (tumor
      necrosis factor-alpha, interleukin (IL)-1alpha, IL-1beta, IL-1 receptor agonist,
      IL-6, IL-10, heat shock proteins, angiotensin I converting enzyme, plasminogen
      activator inhibitor-1) can influence the amount or function of the protein
      produced in response to bacterial stimuli. Evidence is discussed suggesting that
      some of these genetic polymorphisms influence the susceptibility to and outcome
      from sepsis. CONCLUSION: Host genetic variability in the regulatory and coding
      regions of genes for components of the innate immune system may influence the
      susceptibility to and/or outcome from sepsis. The disparate results observed in
      many studies of polymorphisms in sepsis emphasize the need for future studies to
      be larger, to include the analysis of multiple polymorphisms, and to be better
      designed with respect to control populations to identify the degree of influence
      that genetic variability has on sepsis.

PMID- 15857563
TI  - Assessing the quality of case-control association studies on the genetic basis of
      sepsis.
AB  - OBJECTIVE: To define methodological standards that would improve the quality and
      reproducibility of case-control genetic association studies in sepsis. DESIGN:
      Summary of the published standards. RESULTS: Twelve main criteria and measures
      for evaluation of those criteria were developed from a variety of reviews and
      editorials on the subject. CONCLUSIONS: Case-control candidate gene association
      studies represent an important tool for understanding the role that genes play in
      the pathogenesis of sepsis. It is important, however, to understand the
      limitations of these studies and the need for replication.

PMID- 15857565
TI  - Pediatric cancer patients in clinical trials of sepsis: factors that predispose
      to sepsis and stratify outcome.
AB  - OBJECTIVE: To delineate the factors that predispose pediatric oncology and
      hematopoietic stem cell transplant (HSCT) patients to sepsis and to identify
      factors that stratify their outcome. DATA SOURCE: Peer-reviewed literature
      available via MEDLINE search. STUDY SELECTION: All types of study. CONCLUSIONS:
      Pediatric oncology patients account for a relatively high proportion of severe
      sepsis in children. Available data suggest that outcomes among the non-HSCT
      oncology population are not substantially different from that of the general
      population. Data suggest that children with cancer (non-HSCT) who survive their
      septic episode will have a high probability of 6-month survival. In light of
      these findings, pediatric oncology patients are an important source of potential
      candidates for clinical trials of sepsis. In addition, HSCT patients seem to have
      significantly worse outcomes from sepsis than the non-HSCT oncology population,
      and thus, their participation in clinical trials is needed. However, in view of
      these worse outcomes, it is important to stratify the randomization for this
      population and to ensure that studies are adequately powered to assess outcomes
      in this subgroup.

PMID- 15857564
TI  - Factors influencing predisposition to sepsis in children with cancers and
      acquired immunodeficiencies unrelated to human immunodeficiency virus infection.
AB  - OBJECTIVES: The main objectives of this review are to provide insight into the
      various factors that affect the risk of sepsis in immunocompromised children and
      to discuss special issues that should be considered when such patients are
      enrolled in clinical trials. STRATEGY: A literature review was conducted, and
      authoritative references were consulted when appropriate. This was supported by
      discussion among experts at an international consensus conference on pediatric
      sepsis. OUTCOME: The review discusses general issues as they relate to the
      factors that are associated with a predisposition to sepsis in children with
      cancers and non-human immunodeficiency virus (HIV)-related acquired
      immunodeficiencies. The host defects that are associated with specific infections
      are discussed, and an overview of the indicators of immune dysfunction in the
      previously well child is presented. Selected examples of patients with non-HIV
      related acquired immunodeficiencies, including those with cancer or who have
      undergone solid-organ or hematopoietic stem-cell transplants are discussed.
      Special challenges that may affect clinical trials include the altered immune
      response as this relates to the definition of infection and disease and the
      assessment of outcomes and the heterogeneity of study populations due to the
      variable manifestations of immune deficiency states. SUMMARY: Knowledge of the
      factors that are associated with sepsis in immunocompromised patients is
      important when such patients are to be entered into clinical trials on sepsis.
      These factors do not necessarily operate in isolation and may occur concurrently
      or sequentially. With these considerations in mind, clinical trials involving
      immunocompromised children can go forward and will very likely lead to
      significant advances in the care of this understudied population.

PMID- 15857566
TI  - Defining pneumonia in critically ill infants and children.
AB  - OBJECTIVE: To define pneumonia in critically ill children in the intensive care
      unit setting for surveillance of infection and for the design, conduct, and
      evaluation of clinical trials in the prevention and therapy of lower respiratory
      tract infections in this population. DESIGN: Summary of the literature with
      review and consensus by experts in the field. RESULTS: A variety of diagnostic
      criteria from the medical literature, professional societies, and governmental
      health agencies and regulators were identified. Very few of these diagnostic
      criteria have been validated for use in children. We propose definitions for
      definite, possible, and probable pneumonia that build on identified definitions
      in the literature and use combinations of symptoms, signs, and laboratory
      criteria. Gaps in knowledge were identified. CONCLUSIONS: Although pneumonia is
      one of the most common diagnoses in critically ill children, there have been few
      studies validating diagnostic criteria. Definitions for definite, probable, and
      possible community-acquired pneumonia and nosocomial pneumonia were achieved by
      consensus of experts based on guidelines from governmental agencies, professional
      organizations, and published literature. Future research should determine the
      utility of these definitions in the critically ill child and adapt them
      accordingly.

PMID- 15857567
TI  - Sepsis predisposition in children with human immunodeficiency virus.
AB  - OBJECTIVE: To review predisposition to sepsis in children infected with human
      immunodeficiency virus (HIV) in the era of highly active antiretroviral therapy
      (HAART). DESIGN: Summary of the literature with review by experts in the field.
      RESULTS: In industrialized regions, new diagnoses of vertically acquired HIV
      infection are falling due to perinatal interventions. Provision of HAART has
      resulted in an enlarging cohort of clinically stable HIV-infected children, with
      low viral loads and normal CD4 T-lymphocyte counts. Access to HAART in
      "developed" countries has markedly decreased the rate of progression to acquired
      immunodeficiency syndrome, the prevalence of organ-specific complications of HIV,
      the risk of recurrent sepsis, and the high early childhood mortality from HIV
      infection. There are currently no data on whether initiation of HAART during
      acute sepsis reduces short-term morbidity or mortality. Undiagnosed,
      antiretroviral-naive, HIV-infected infants still present sporadically with
      opportunistic infections such as Pneumocystis jiroveci and cytomegalovirus
      pneumonia. HIV-infected children have a greater burden of disease due to viral,
      bacterial, and fungal sepsis, and the case fatality rate for nonopportunistic
      infections may be greater than in non-HIV-infected children. In "developing"
      countries, with limited access to HAART, the natural history of HIV infection has
      altered very little, with the majority of infected children dying from either
      opportunistic or nonopportunistic disease before 3 yrs of age. CONCLUSION:
      Pediatric HIV infection is not a homogeneous condition in the era of HAART.
      Susceptibility to sepsis, morbidity, and mortality differ according to stage of
      disease, access to HAART, and virologic and immunologic response to treatment.
      These issues should be considered if HIV-infected children are to be enrolled and
      stratified in clinical trials.

PMID- 15857568
TI  - Congenital immunodeficiencies and sepsis.
AB  - OBJECTIVE: Because a hallmark of congenital immunodeficiency disorders is
      susceptibility to recurrent, unusual and/or severe infections, an effort was
      undertaken to identify a subset of these patients with an increased risk for
      sepsis. DESIGN: Literature review. RESULTS: Twenty congenital immunodeficiency
      disorders were identified with increased sepsis susceptibility. CONCLUSION:
      Distinguishing patients with congenital immunodeficiencies from others with
      sepsis has important implications for the future well-being of the
      immunodeficient patient because many of the diseases are modified favorably by
      appropriate treatment. In addition, better understanding of sepsis in the setting
      of congenital immunodeficiency has numerous implications for both
      immunodeficiency and sepsis research. As a group, these disorders define
      components of the human immune system that are essential for defense against
      severe infection and demonstrate immunologic themes underlying sepsis
      susceptibility.

PMID- 15857569
TI  - Combined analysis of 635 patients confirms an age-related association of the
      serotonin 2A receptor gene with tardive dyskinesia and specificity for the non
      orofacial subtype.
AB  - Tardive dyskinesia (TD) is an important limiting factor in the use of typical
      antipsychotic drugs. Genetic variability in the serotonin 2A (5-HT(2A)) receptor
      may influence risk for TD but the results of prior studies are not confirmatory.
      The objective of this study was to determine association of T102C and His452Tyr
      polymorphisms in the 5-HT(2A) receptor gene (HTR(2A)) with TD in a large,
      multicentre patient sample. The design employed case-control analysis controlling
      for possible confounders using pooled, original data from published and available
      unpublished samples and employing logistic regression, analysis of variance and
      meta-analysis. The study sample consisted of 635 patients with schizophrenia or
      schizoaffective disorder (256 with TD and 379 without TD) drawn from five
      research centres, divided into six groups based on population origin. The main
      outcome measure was association of a categorical diagnosis of TD based on the
      Research Diagnostic Criteria for TD with HTR(2A) T102C and His452Tyr genotypes
      and haplotypes. The findings indicate significant association of TD with HTR(2A)
      T102C genotype (p=0.002) over and above the effect of population group, also when
      controlling for age and gender (p=0.0008), but not with His452Tyr genotype. The
      T102C genotype was significantly associated with TD in older (>median age 47 yr,
      p=0.002) but not younger patients and in patients with non-orofacial (limb
      truncal) (p=0.001) but not orofacial TD. By meta-analysis the Mantel-Haenszel (M
      H) pooled odds ratio (OR) across all the available data was 1.64. A T102C
      His452Tyr haplotype was significantly associated with TD (p=0.0008). These
      findings confirm that genetic variability in HTR(2A) contributes a small but
      significant degree of risk for the expression of TD, particularly in older
      patients and specifically for the non-orofacial (limb-truncal) type. Together
      with other genetic variants associated with TD the findings could be used to
      assess risk in patients who are candidates for treatment with typical
      antipsychotic medications.

PMID- 15857570
TI  - Case series on the use of aripiprazole for Tourette syndrome.

PMID- 15857571
TI  - Combined alpha2 and D2/3 receptor blockade enhances cortical glutamatergic
      transmission and reverses cognitive impairment in the rat.
AB  - The alpha(2) adrenoceptor antagonist idazoxan enhances antipsychotic efficacy of
      classical dopamine D(2) antagonists in treatment-resistant schizophrenia. The
      mechanisms are not fully understood, but we have previously shown that the
      combination of idazoxan with the D(2/3) receptor antagonist raclopride, similarly
      to clozapine but not classical antipsychotic drugs, augments dopamine efflux in
      the prefrontal cortex, and also generates an enhanced suppression of the
      conditioned avoidance response. We have now investigated the effects of
      clozapine, raclopride, idazoxan and the combination of raclopride and idazoxan on
      (i) electrically evoked excitatory post-synaptic potentials and currents in
      pyramidal cells of the rat medial prefrontal cortex, using intracellular
      electrophysiological recording in vitro, (ii) the impaired cognitive function
      induced by the selective N-methyl-D-aspartate (NMDA) receptor antagonist MK-801,
      using the 8-arm radial maze test, (iii) the in-vivo D2, alpha(2A) and alpha(2C)
      receptor occupancies of these pharmacological treatments, using ex-vivo
      autoradiography. Whereas neither idazoxan nor raclopride alone had any effect,
      the combination exerted the same facilitation of glutamatergic transmission in
      rat prefrontal pyramidal neurons as clozapine, and this effect was found to be
      mediated by dopamine acting at D(1) receptors. Similarly to clozapine, the
      combination of idazoxan and raclopride also completely reversed the working
      memory impairment in rats induced by MK-801. Moreover, these effects of the two
      treatment regimes were obtained at similar occupancies at D(2), alpha(2A) and
      alpha(2C) receptors respectively. Our results provide novel neurobiological and
      behavioural support for a pro-cognitive effect of adjunctive use of idazoxan with
      antipsychotic drugs that lack appreciable alpha(2) adrenoceptor-blocking
      properties, and define presynaptic alpha(2) adrenoceptors as major targets in
      antipsychotic drug development.

PMID- 15857572
TI  - Effects of norepinephrine and histamine on vascular resistance in isolated
      perfused mouse liver.
AB  - Mice have frequently been used for a variety of physiological studies because of
      the development of genetic engineering. However, the characteristics of hepatic
      vessels such as the vascular resistance distribution and the reactivity to
      various vasoconstrictors are not known in mice. We therefore determined the basal
      levels of segmental vascular resistances and the effects of histamine and
      norepinephrine on the vascular resistance distribution of mice. The liver of male
      non-inbred ddY mice was excised and perfused via the portal vein with 5% bovine
      albumin-Krebs solution at a constant flow rate. The sinusoidal pressure was
      measured by the double occlusion pressure and used to determine the presinusoidal
      (R(pre)) and postsinusoidal (R(post)) resistances. The basal R(post) comprised 53
      +/- 1% of the total hepatic vascular resistance. The norepinephrine and histamine
      increased R(pre) in a greater magnitude than R(post) with liver weight loss.
      However, the response to histamine was weaker than that to norepinephrine.
      Moreover, histamine-induced vasoconstriction showed tachyphylaxis. In conclusion,
      the presinusoidal and postsinusoidal resistances of mouse livers were similar in
      magnitude. The presinusoidal vessels predominantly contract in response to
      norepinephrine and histamine in mouse livers.

PMID- 15857573
TI  - Difference in propagation of Ca2+ release in atrial and ventricular myocytes.
AB  - Intracellular [Ca2+] ([Ca2+]i) was imaged in atrial and ventricular rat myocytes
      by means of a high-speed Nipkow confocal microscope. Atrial myocytes with an
      absent t-tubule system on 8-di- ANEPPS staining showed an initial rise in Ca2+ at
      the periphery of the cell, which propagated to the interior of the cell.
      Ventricular myocytes showed a uniform rise in [Ca2+]i after electrical
      stimulation, consistent with a prominent t-tubular network. In atrial myocytes,
      there was a much shorter time between the peak of the [Ca2+]i transient and the
      peak contraction as compared to ventricular myocytes. A regional release of Ca2+
      induced by an exposure of one end of the myocyte to caffeine with a rapid
      solution switcher resulted in a uniform propagation of Ca2+ down the length of
      the cell in atrial myocytes, but we found no propagation in ventricular myocytes.
      A staining with rhodamine 123 indicated a much greater density of mitochondria in
      ventricular myocytes than in atrial myocytes. Thus the atrial myocytes display a
      lack of "local control" of Ca2+ release, with propagation after the Ca2+ release
      at the periphery induced by stimulation or at one end of the cell induced by
      exposure to caffeine. Ventricular myocytes showed the presence of local control,
      as indicated by an absence of the propagation of a local caffeine-induced Ca2+
      transient. We suggest that this finding, as well as a reduced delay between the
      peak of the [Ca2+]i transient and the peak shortening in atrial myocytes, could
      be due in part to reduced Ca2+ buffering provided by mitochondria in atrial
      myocytes as opposed to ventricular myocytes.

PMID- 15857574
TI  - Reduction of cortico-spinal excitability by transcranial magnetic stimulation at
      predictable timing.
AB  - Electrophysiological studies have shown that cortico-spinal excitability
      increases during the motor preparation period in reaction time (RT) paradigms.
      However, there is a line of contradictory evidence with transcranial magnetic
      stimulation (TMS) showing that its excitability is reduced during the preparation
      period. In these studies, the subjects can predict the TMS timings. Thus we
      investigated how the predictability of TMS timing affects cortico-spinal
      excitability. A single-pulse TMS was delivered to the hand section of the left
      motor cortex while seven right-handed subjects relaxed their hands in a flexed
      position. We prepared three conditions: (i) in the semi-PREDICTABLE condition,
      two visual stimuli at 500 ms interval were presented and the TMS was delivered
      either 0, 125, 250, 375, or 500 ms after the first stimulus; (ii) in the
      PREDICTABLE condition, the TMS was provided only at 500 ms after the first
      stimulus; (iii) in the UNPREDICTABLE condition, no visual cue preceded the TMS.
      We recorded motor evoked potentials (MEPs) from the wrist flexor and extensor
      muscles. We found a significant reduction of MEP amplitude in the flexor muscles
      in both the PREDICTABLE and semi-PREDICTABLE conditions, but not in the
      UNPREDICTABLE condition. These results showed that the predictability of TMS per
      se, without the preparation of motor outputs, can reduce cortico-spinal
      excitability.

PMID- 15857575
TI  - Changes in nitric oxide and inducible nitric oxide synthase following stretch
      induced injury to the tibialis anterior muscle of rabbit.
AB  - This study investigated the changes in nitric oxide (NO) together with inducible
      nitric oxide synthase (iNOS) content and enzyme activity at 0, 4, 12, 24, and 48
      h following acute muscle stretch injury. A single stretch injury was induced to
      the tibialis anterior muscle of 30 male New Zealand white rabbits (n = 6 at each
      time point). Injured and uninjured contralateral sham-operated muscles were
      harvested and analyzed for NO levels, iNOS content, and iNOS activity at each
      time point. Furthermore, three animals were used to estimate baseline NO levels
      and iNOS activity. There was a progressive reduction in NO content in the injured
      and the sham-operated muscles up to 24 h postoperation and stretch injury (p <
      0.05). At 48 h postinjury, however, NO levels were 146% higher in injured muscles
      than in sham-operated muscles (p < 0.05). iNOS protein content was higher at 4 h
      and 48 h in injured versus shamoperated muscles (p < 0.05). Similarly, iNOS
      activity was higher at 4 h (p < 0.05) and at 48 h (p < 0.01) in injured versus
      sham-operated muscles. These results suggest that NO may play an active role
      during the postinjury recovery of skeletal muscle modulated by iNOS expression.

PMID- 15857576
TI  - The crystal structure of the non-liganded 14-3-3sigma protein: insights into
      determinants of isoform specific ligand binding and dimerization.
AB  - Seven different, but highly conserved 14-3-3 proteins are involved in diverse
      signaling pathways in human cells. It is unclear how the 14-3-3sigma isoform, a
      transcriptional target of p53, exerts its inhibitory effect on the cell cycle in
      the presence of other 14-3-3 isoforms, which are constitutively expressed at high
      levels. In order to identify structural differences between the 14-3-3 isoforms,
      we solved the crystal structure of the human 14-3-3sigma protein at a resolution
      of 2.8 Angstroms and compared it to the known structures of 14-3-3zeta and 14-3
      3tau. The global architecture of the 14-3-3sigma fold is similar to the
      previously determined structures of 14-3-3zeta and 14-3-3t: two 14-3-3sigma
      molecules form a cup-shaped dimer. Significant differences between these 14-3-3
      isoforms were detected adjacent to the amphipathic groove, which mediates the
      binding to phosphorylated consensus motifs in 14-3-3-ligands. Another specificity
      determining region is localized between amino-acids 203 to 215. These differences
      presumably select for the interaction with specific ligands, which may explain
      the different biological functions of the respective 14-3-3 isoforms.
      Furthermore, the two 14-3-3sigma molecules forming a dimer differ by the spatial
      position of the ninth helix, which is shifted to the inside of the ligand
      interaction surface, thus indicating adaptability of this part of the molecule.
      In addition, 5 non-conserved residues are located at the interface between two 14
      3-3sigma proteins forming a dimer and represent candidate determinants of homo-
      and hetero-dimerization specificity. The structural differences among the 14-3-3
      isoforms described here presumably contribute to isoform-specific interactions
      and functions.

PMID- 15857577
TI  - 14-3-3 proteins--an update.
AB  - 14-3-3 is a highly conserved acidic protein family, composed of seven isoforms in
      mammals. 14-3-3 protein can interact with over 200 target proteins by
      phosphoserine-dependent and phosphoserine-independent manners. Little is known
      about the consequences of these interactions, and thus are the subjects of
      ongoing studies. 14-3-3 controls cell cycle, cell growth, differentiation,
      survival, apoptosis, migration and spreading. Recent studies have revealed new
      mechanisms and new functions of 14-3-3, giving us more insights on this
      fascinating and complex family of proteins. Of all the seven isoforms, 14-3
      3sigma seems to be directly involved in human cancer. 14-3-3sigma itself is
      subject to regulation by p53 upon DNA damage and by epigenetic deregulation. Gene
      silencing of 14-3-3sigma by CpG methylation has been found in many human cancer
      types. This suggests that therapy-targeting 14-3-3sigma may be beneficial for
      future cancer treatment.

PMID- 15857578
TI  - The role of epigenetic inactivation of 14-3-3sigma in human cancer.
AB  - Cancer cells show characteristic alterations in DNA methylation patterns.
      Aberrant CpG methylation of specific promoters results in inactivation of tumor
      suppressor genes and therefore plays an important role in carcinogenesis. The p53
      regulated gene 14-3-3sigma undergoes frequent epigenetic silencing in several
      types of cancer, including carcinoma of the breast, prostate, and skin,
      suggesting that the loss of 14-3-3sigma expression may be causally involved in
      tumor progression. Functional studies demonstrated that 14-3-3sigma is involved
      in cell-cycle control and prevents the accumulation of chromosomal damage. The
      recent identification of novel 14-3-3sigma-associated proteins by a targeted
      proteomics approach implies that 14-3-3sigma regulates diverse cellular
      processes, which may become deregulated after silencing of 14-3-3sigma expression
      in cancer cells.

PMID- 15857579
TI  - Epigenetic alterations in gastric carcinogenesis.
AB  - Gastric cancer is believed to result in part from the accumulation of multiple
      genetic alterations leading to oncogene overexpression and tumor suppressor loss.
      Epigenetic alterations as a distinct and crucial mechanism to silence a variety
      of methylated tissue-specific and imprinted genes, have been extensively studied
      in gastric carcinoma and play important roles in gastric carcinogenesis. This
      review will briefly discuss the basic aspects of DNA methylation and CpG island
      methylation, in particular the epigenetic alterations of certain critical genes
      implicated in gastric carcinogenesis and its relevance of clinical implications.

PMID- 15857580
TI  - Methyl-CpG binding proteins in the nervous system.
AB  - Classical methyl-CpG binding proteins contain the conserved DNA binding motif
      methyl-cytosine binding domain (MBD), which preferentially binds to methylated
      CpG dinucleotides. These proteins serve as transcriptional repressors, mediating
      gene silencing via DNA cytosine methylation. Mutations in methyl-CpG binding
      protein 2 (MeCP2) have been linked to the human mental retardation disorder Rett
      syndrome, suggesting an important role for methyl-CpG binding proteins in brain
      development and function. This mini-review summarizes the recent advances in
      studying the diverse functions of MeCP2 as a prototype for other methyl-CpG
      binding proteins in the development and function of the vertebrate nervous
      system.

PMID- 15857581
TI  - Epigenetic changes in virus-associated human cancers.
AB  - Epigenetics of human cancer becomes an area of emerging research direction due to
      a growing understanding of specific epigenetic pathways and rapid development of
      detection technologies. Aberrant promoter hypermethylation is a prevalent
      phenonmena in human cancers. Tumor suppressor genes are often hypermethylated due
      to the increased activity or deregulation of DNMTs. Increasing evidence also
      reveals that viral genes are one of the key players in regulating DNA
      methylation. In this review, we will focus on hypermethylation and tumor
      suppressor gene silencing and the signal pathways that are involved, particularly
      in cancers closely associated with the hepatitis B virus, simian virus 40 (SV40),
      and Epstein-Barr virus. In addition, we will discuss current technologies for
      genome-wide detection of epigenetically regulated targets, which allow for
      systematic DNA hypermethylation analysis. The study of epigenetic changes should
      provide a global view of gene profile in cancer, and epigenetic markers could be
      used for early detection, prognosis, and therapy of cancer.

PMID- 15857582
TI  - The altered DNA methylation pattern and its implications in liver cancer.
AB  - DNA methylation is the most intensively studied epigenetic phenomenon,
      disturbances of which result in changes in gene transcription, thus exerting
      drastic imparts onto biological behaviors of cancer. Both the global
      demethylation and the local hypermethylation have been widely reported in all
      types of tumors, providing both challenges and opportunities for a better
      understanding and eventually controlling of the malignance. However, we are still
      in the very early stage of information accumulation concerning the tumor
      associated changes in DNA methylation pattern. A number of excellent recent
      reviews have covered this issue in depth. Therefore, this review will summarize
      our recent data on DNA methylation profiling in cancers. Perspectives for the
      future direction in this dynamic and exciting field will also be given.

PMID- 15857583
TI  - Tudor and its domains: germ cell formation from a Tudor perspective.
AB  - In many metazoan species, germ cell formation requires the germ plasm, a
      specialized cytoplasm which often contains electron dense structures. Genes
      required for germ cell formation in Drosophila have been isolated predominantly
      in screens for maternal-effect mutations. One such gene is tudor (tud); without
      proper tud function germ cell formation does not occur. Unlike other genes
      involved in Drosophila germ cell specification tud is dispensable for other
      somatic functions such as abdominal patterning. It is not known how TUD
      contributes at a molecular level to germ cell formation but in tud mutants, polar
      granule formation is severely compromised, and mitochondrially encoded ribosomal
      RNAs do not localize to the polar granule. TUD is composed of 11 repeats of the
      protein motif called the Tudor domain. There are similar proteins to TUD in the
      germ line of other metazoan species including mice. Probable vertebrate
      orthologues of Drosophila genes involved in germ cell specification will be
      discussed.

PMID- 15857584
TI  - Chromatin domain boundaries: insulators and beyond.
AB  - The eukaryotic genome is organized into functionally and structurally distinct
      domains, representing regulatory units for gene expression and chromosome
      behavior. DNA sequences that mark the border between adjacent domains are the
      insulators or boundary elements, which are required in maintenance of the
      function of different domains. Some insulators need others enable to play
      insulation activity. Chromatin domains are defined by distinct sets of post
      translationally modified histones. Recent studies show that these histone
      modifications are also involved in establishment of sharp chromatin boundaries in
      order to prevent the spreading of distinct domains. Additionally, in some loci,
      the high-order chromatin structures for long-range looping interactions also have
      boundary activities, suggesting a correlation between insulators and chromatin
      loop domains. In this review, we will discuss recent progress in the field of
      chromatin domain boundaries.

PMID- 15857586
TI  - Breast cancer - changing role of the health care providers.

PMID- 15857587
TI  - Role of grey scale ultrasound in benign and malignant breast lesions.
AB  - OBJECTIVE: To evaluate the sensitivity and specificity of ultrasound in diagnosis
      of benign and malignant disease in correlation with histopathological findings.
      DESIGN: A comparative study. PLACE AND DURATION OF STUDY: Diagnostic Radiology
      Department of PNS Shifa, Karachi, from January 2000 to July 2002. PATIENTS AND
      METHODS: Adult female patients presenting with breast lump were included. Grey
      scale ultrasound was done with high frequency probe. Findings were compared with
      histopathology. The sensitivity and specificity was determined. RESULTS: Eighty
      five female patients with positive clinical findings were differentiated into
      benign (n =45, 52.9%), intermediate (n =15, 17.6%) and malignant (n =25, 29.4%),
      by ultrasound examination. Only one (2.2%) benign lesion was found malignant on
      histopathology, 8 (32%) cases of malignant group were benign on histopathology.
      The sensitivity of ultrasound for malignant lesion was 95.24% and specificity was
      68.75% for a benign lesion. Our results were compatible with international
      studies. CONCLUSION: Ultrasound of breast is very useful in evaluating breast
      lumps. This modality is, however, not a good screening tool. When combined with
      clinical evaluation and mammographic studies, a subset of patients can be
      identified which do not require biopsy. This will not only save the cost but will
      also alley the anxiety of patients.

PMID- 15857588
TI  - Cytohistopathological correlation of C3 and C4 breast lesions.
AB  - OBJECTIVE: To conduct an audit of smears in cytological categories C3 and C4 of
      fine-needle aspirates from breast lesions in comparison with histopathological
      diagnoses. DESIGN: Comparative, cross-sectional study. PLACE AND DURATION OF
      STUDY: Department of Histopathology, Armed Forces Institute of Pathology (AFIP),
      Rawalpindi from January to December 2002. PATIENTS AND METHODS: Out of all
      patients referred to AFIP, Rawalpindi for aspiration of breast masses, those
      adjudged C3 and C4 were chosen for this study. History, clinical details and
      mammographic findings were noted. Aspirated smears were stained with haematoxylin
      and eosin as well as a Romanovsky dye. On excision or incision biopsy of these
      lesions, the cytological findings were compared with those on paraffin-embedded
      histological sections. RESULTS: The total number of patients in these two
      categories was 54. Surgical specimens of 3 cases were found inadequate for
      assessment. Of the remaining 51 cases, 13 were categorised C3 and 38 C4.
      Sensitivity of 92%, specificity of 83% and accuracy of 90% were attained.
      Positive and negative predictive values were 95% and 77% respectively.
      CONCLUSION: Categories C3 and C4 are areas where the cytopathologist is in doubt
      as to the benign or malignant nature of a breast mass. High sensitivity, positive
      predictive value and accuracy, being the hallmarks of a good screening procedure,
      underscore the validity of the technique.

PMID- 15857589
TI  - Toxicity profile and objective response of paclitaxel in metastatic breast
      cancer.
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of 1-hour weekly Paclitaxel in
      metastatic breast cancer along with evaluation of overall survival. DESIGN: A
      phase II interventional trial. PLACE AND DURATION OF STUDY: Oncology Department,
      Combined Military Hospital, Rawalpindi, between August 2001 to July 2003.
      PATIENTS AND METHODS: Thirty-six patients were enrolled in the study. All
      patients with histologically confirmed and bi-dimensionally measurable metastatic
      breast cancer who had received previously either chemotherapy or hormone therapy
      were included in the study. Paclitaxel was administered in 1-hour weekly infusion
      in a dose of 100 mg/m2 for 12 doses. RESULTS: All patients had received previous
      chemotherapy with either CAF or CMF. Twenty-five patients had also received
      hormone therapy, 61% had two or more metastatic sites involved, and lung was the
      common site of involvement. Complete response was observed in 4 (11.1%) patients,
      partial response in 14 (38.8%) patients, with an overall response rate of 50.0%.
      Clinical benefit was 94.4% and median overall survival was 11 months. Treatment
      was well-tolerated with no grade 3 or 4 toxicity. Common side effects were
      arthralgias, myalgias and neutropenia. CONCLUSION: Treatment with 1-hour weekly
      infusion of Paclitaxel is a well-tolerated chemotherapy with a substantial degree
      of efficacy in patients with metastatic breast cancer.

PMID- 15857590
TI  - Efficacy of letrozole for advanced breast cancer in postmenopausal patients.
AB  - OBJECTIVE: To evaluate the clinical benefit and tolerability of letrozole after
      tamoxifen failure in locally advanced, recurrent or metastatic breast cancer in
      postmenopausal patients. DESIGN: A phase II non-randomized trial. PLACE AND
      DURATION OF STUDY: Oncology Department, Combined Military Hospital, Rawalpindi,
      from March 1999 to February 2001 over a period of 2 years. PATIENTS AND METHODS:
      One hundred and seventeen patients with tamoxifen failure were treated with
      letrozole 2.5 mg once daily, through oral route. All the accrued patients were
      either estrogen/progesterone receptor positive or unknown with KPS of more than
      50%. Patients who had prior hormone therapy other than tamoxifen, or more than
      one chemotherapy for recurrent or advanced disease were not enrolled in the
      study. Time to progression (TTP) was the primary objective, whereas objective
      response (OR), duration and rate of clinical benefit (complete response + partial
      response + stable disease >6 months), tolerability and effects on quality of life
      were the secondary end points. RESULTS: The clinical benefit was 47.0% with an
      objective response of 28.2%. The objective response and median time to
      progression in soft tissue disease was better than in the visceral and bone
      disease. The median time to progression for patients having positive estrogen
      receptor / progesterone receptors (ER / PR) was 9.5 months which is slightly
      higher than in patients having unknown ER / PR status. The treatment with
      letrozole was well-tolerated with side effects observed in only 14 patients.
      CONCLUSION: Letrozole is an effective hormone therapy after tamoxifen failure
      since it has significant clinical benefit and objective response. It can be
      safely used as second line hormone therapy in postmenopausal patients with
      locally advanced or metastatic breast cancer.

PMID- 15857591
TI  - Role of FNA cytology in the management of carcinoma breast.
AB  - OBJECTIVE: To evaluate the utility and role of fine needle aspiration cytology
      (FNAC) in essential surgical management of carcinoma breast. DESIGN: Descriptive
      study. PLACE AND DURATION OF STUDY: PNS Shifa, Karachi, Combined Military
      Hospital (CMH), Pannu Aqil and PNS Rahat from August 1998 to August 2003 [05
      years]. PATIENTS AND METHODS: The study included one hundred cases of carcinoma
      of breast-97 females and 3 males, confirmed on histopathological examination and
      surgically treated at PNS Shifa, CMH Pano Aqil and PNS Rahat. FNA cytology was
      the primary tool of investigation in all. The benefit of the procedure was
      evaluated considering the ease of the procedure, cost, safety, reliability as
      screening procedure and its effect on sparing the patients from excision or
      incision biopsy and thus additional anesthesia. RESULTS: Sensitivity of the
      procedure was 78%, specificity 100%, predictve value 100% and overall diagnostic
      accuracy 72%. Out of 78 cases, diagnosed as positive for malignancy on FNAC and
      later confirmed by histopathological examination, 58 underwent frozen section
      examination followed by definitive surgery (modified radical mastectomy).
      Remaining 20 cases underwent additional core biopsy. Out of these, 12 cases
      underwent definitive surgery without frozen section and 8 patients underwent
      frozen section examination followed by definitive surgery. A single case required
      general anesthesia (GA) while the patients undergoing core biopsy required a
      local anesthesia (LA) as well. Cases remaining undiagnosed by FNA-cytology (22
      cases) required either an excision biopsy (17 cases) or incision biopsy (5 cases)
      under GA followed by definitive surgery, thus requiring general anesthesia twice
      during the management. CONCLUSION: FNA-cytology can positively affect the
      surgical management of carcinoma breast. It can be utilized to select the
      patients for frozen section examination and can thus spare the patients from
      additional procedure of excision or incision biopsy under separate anesthesia. It
      may be adopted as a routine procedure in surgical outpatient.

PMID- 15857592
TI  - Comparison of fine needle aspiration cytology with excision biopsy of breast
      lump.
AB  - OBJECTIVE: To evaluate the results of fine needle aspiration cytology (FNAC) of
      breast lump by histopathology of excision biopsy specimen in the same group of
      patients. DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Department of
      Surgery, Federal Government Services Hospital, Islamabad from October, 2000 to
      March, 2001. MATERIALS AND METHODS: There were 50 patients in the study, who were
      subjected to fine needle aspiration cytology with a needle of 22G mounted on 20
      cc syringe. Smears were fixed on the slides with 95% alcohol and later stained
      with hematoxylin and eosin stain. After FNAC, all the patients were subjected to
      excision biopsy. The specimen were reported by the Histopathologist and results
      evaluated and compared. RESULTS: All patients were among the total number of 61
      FNAC performed, conclusive malignancy (C5) was found in 20(40%) patients and in
      1(2%) patient, malignancy was suspected (C4). Conclusive benign lesions (C2) were
      found in 26(52%) patients and 2 patients had atypia i.e. (C3). Inadequate
      specimen (C1) was found in 2(4%) patients. On excision biopsy, 22(44%) patients
      had malignant lumps and 28(56%) benign. FNAC was able to detect 20 malignant
      lumps with sensitivity of 90.90%. All of them were also reported malignant on
      excision biopsy with specificity of 100%. False positive were zero and false
      negative were 9.1%. CONCLUSION: FNAC is simple, quick, safe, tolerable,
      cosmetically acceptable, reliable and cost-effective method of determining
      histology of breast lumps. The absence of false positives conclusively confirmed
      its place not only as a complimentary adjunct but also a substitute of excision
      biopsy in majority of instances.

PMID- 15857593
TI  - Sentinel node localization in breast carcinoma.
AB  - OBJECTIVE: To determine the success rate of sentinel node dissection and the
      sensitivity of sentinel node to determine the presence of axillary node
      metastasis in women with clinically node negative breast cancer. DESIGN: Case
      series. PLACE AND DURATION OF STUDY: The study was conducted at Department of
      General Surgery Pakistan Institute of Medical Sciences, Islamabad (PIMS) and
      Nuclear Oncology and Radiotherapy Institute, Islamabad (NORI) from January 2002
      to December 2003. PATIENTS AND METHODS: A total of 15 patients of early carcinoma
      breast were recruited in the study. Five patients were injected with radiocolloid
      and later with isosulfan blue in the subareolar region. Ten patients were given
      isosulfan blue only. All the patients were subjected to standard axillary
      clearance after sentinel node biopsy through separate incisions. Sentinel node
      was examined by intra-operative frozen section and all of the dissected lymph
      nodes were examined histopathologically for tumour deposits. RESULTS: Sentinel
      lymph node was successfully excised in all the cases 15/15 (100%). In 14 of the
      patients the sentinel node pathology was truly predictive of axillary nodal
      status. Sensitivity of the test was 93.33% and the positive predictive value was
      100%. CONCLUSION: Sentinel node biopsy should be followed by standard axillary
      lymph adenectomy until the results of multiple prospective randomized trials
      define the role of this technique in the management of carcinoma breast.

PMID- 15857594
TI  - Locoregional recurrence after management of carcinoma breast.
AB  - OBJECTIVE: To determine the rate of locoregional recurrence, disease-free
      interval, site and pattern of locoregional recurrence and the significance of
      different factors for predicting locoregional recurrence in patients with stage
      II and III carcinoma breast. DESIGN: Descriptive study. PLACE AND DURATION OF
      STUDY: Surgical Unit-1, Jinnah Hospital, Lahore from September 2001 to December
      2002. PATIENTS AND METHODS: Criteria for including patients in this study was
      female patients with stage II and III carcinoma breast who presented in our unit
      from 1995-2002 and underwent surgical (modified radical mastectomy, simple
      mastectomy with axillary sampling) and non-surgical (chemotherapy, radiotherapy,
      hormonal therapy) treatment of carcinoma breast. Record of 98 patients was
      evaluated for rate of locoregional recurrence, disease-free interval, site and
      pattern of locoregional recurrence and different clinical factors like stage of
      carcinoma, tumour size, lymph node status and histopathology were assessed for
      association with locoregional recurrence. RESULTS: After a mean follow-up of 3.5
      years, 17 patients developed locoregional recurrence. Mean disease free interval
      in stage II was 30 months and only 9.5 months in stage III. Lymph node positivity
      was associated with locoregional recurrence (p-value<0.05). Chest wall was
      commonest site of recurrence (73%). Single spot recurrence was common in stage II
      whereas multiple spot recurrence and field change was more common in stage III.
      Addition of radiotherapy to surgery decreased the locoregional recurrence but
      chemotherapy had no significant effect on prevention of locoregional recurrence.
      CONCLUSION: In this series 17.34 % patients developed locoregional recurrence for
      mean follow-up duration of 3.5 years. Mean disease-free interval was 20.52
      months. Lymph node involvement had significant correlation with LRR.

PMID- 15857595
TI  - Typing and grading of cytological category C5 breast lesions.
AB  - OBJECTIVE: To determine the tumour type, cytological grade and nuclear grade on
      fine-needle aspiration smears in cytological category C5 breast lesions and
      compare them with histopathological findings. DESIGN: Cross-sectional, cohort.
      PLACE AND DURATION OF STUDY: Department of Histopathology, Armed Forces Institute
      of Pathology (AFIP), Rawalpindi from January to December 2002. SUBJECTS AND
      METHODS: Out of all patients referred to AFIP, Rawalpindi for fine-needle
      aspiration of breast masses, those adjudged C5 (malignant) were chosen for this
      study. History, clinical details and mammographic findings were noted. Aspirated
      smears were examined and an attempt was made to ascertain tumour type,
      cytological grade and nuclear grade. On excision of these lesions, the
      cytological findings were compared with those on paraffin-embedded histological
      sections. RESULTS: A total of 71 patients were included in this study. Of these,
      64 (90.14%) were cytologically diagnosed as ductal carcinoma, 4 (5.63%) lobular
      carcinoma, 2 (2.82%) mucinous carcinoma and 1 (1.41%) as medullary carcinoma.
      Seventy (98.60%) tumours were correctly typed on aspiration smears. Sixty-eight
      (95.77%) cases were cytologically graded with accuracy. Nuclear grading was even
      better on cytology and, excluding one malignant lymphoma, all 70 (100%) smears
      were assessed correctly. CONCLUSION: Overall efficiency of the tumour typing,
      cytological grading and nuclear grading on aspirated material turned out to be
      quite accurate. In expert hands, cytological examination can be of great help in
      pre-operative planning and in cases where tumour morphology in paraffin-embedded
      material has been distorted by neo-adjuvant therapy prior to excision.

PMID- 15857596
TI  - Prognostic value of proliferating cell nuclear antigen (PCNA) in infiltrating
      ductal carcinoma breast.
AB  - OBJECTIVE: To assess the independent and interdependent prognostic value of
      proliferating cell nuclear antigen (PCNA) in carcinoma of breast in our female
      population and its association with pathologic variables and disease outcome.
      DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Section of
      Histopathology, Department of Pathology and Microbiology, The Aga Khan
      University, Karachi from January 1992 to December 1997. PATIENTS AND METHODS: All
      cases diagnosed with invasive ductal carcinomas (IDC) of breast with lymph nodes
      sampling were included. The expression of PCNA was analyzed on tumor specimens of
      IDC breast. These patients also had axillary lymph node sampling. The expression
      of PCNA protein was analyzed immunohistochemically by PAP technique. Patients
      were followed for a median duration of 48 months. RESULTS: The percentage of PCNA
      positive tumor cells was estimated semi-quantitatively. Positivity was seen in
      every case, mean PCNA positivity was 27% (range 10-80) with a median of 28%. The
      <25% positivity was seen in 149 (47%) cases, and >25% positivity seen in 166
      (53%) cases. According to the pathological grading lowest mean PCNA was seen in
      grade-I i.e., 26% tumor cells showed nuclear reactivity to PCNA followed by grade
      II 30% and grade-III 33%. PCNA categorical expression was significantly
      correlated with histological differentiation, (p<0.05) and tumor size (p<0.01).
      Distant metastases were seen in>25% positive cases (p<0.05). PCNA expression when
      correlated with overall survival, showed significant correlation between
      categorical PCNA (p<0.05). At a median follow-up of 48 months, 66% of <25 PCNA
      positive patients died with an overall survival of 3.16 years and disease-free
      survival of 2.5 years, among >25% PCNA positive patients 77% died with an overall
      survival of 2.7 years and a disease-free survival of 2.2 years. CONCLUSION: In
      this study PCNA proved to be an independent prognostic indicator in predicting
      disease-free and overall survival in breast carcinoma patients.

PMID- 15857597
TI  - Breast cancer: steroid receptors and other prognostic indicators.
AB  - OBJECTIVE: To correlate hormone receptor status in breast cancer with patient's
      age, tumor size, type, grade and lymph node metastasis. DESIGN: A descriptive
      study. PLACE AND DURATION OF STUDY: Department of Histopathology, Liaquat
      National Postgraduate Medical Center, Karachi, from January 2002 to March 2003.
      PATIENTS AND METHODS: One hundred and fifty patients of breast cancer were
      studied. Estrogen and progesterone receptor status was evaluated by
      immunohistochemistry. This was correlated with patients' age, tumor size, type,
      grade and lymph node status. RESULTS: Out of 150 cases, 55% of cases were
      estrogen receptor (ER) negative progesterone receptor ( PR) negative. Older women
      tended to have more steroid receptor reactivity as compared with younger ones. ER
      positivity decreased with increasing tumor size and grade, however, no
      significant correlation was seen with lymph node metastasis. Majority of the
      tumors showing ERPR positivity were infiltrating ductal carcinoma-not otherwise
      specified type. CONCLUSION: This study reports a significantly higher incidence
      of ER negative PR negative phenotype in breast cancer patients. This observation
      is different as compared with that in western literature where ER positive PR
      positive phenotype is greater than the negative phenotype suggesting that breast
      cancer in our patients may have different disease pattern and biology.

PMID- 15857598
TI  - Tuberculous mastitis.
AB  - OBJECTIVE: To find out the different clinical presentations of breast
      tuberculosis and its treatment outcome. DESIGN: An observational study. PLACE AND
      DURATION OF STUDY: Surgical ward 3 of Jinnah Postgraduate Medical Centre, Karachi
      from June 2001 to November 2003. SUBJECTS AND METHODS: Fifty consecutive female
      patients above 13 years presenting with breast lump, multiple sinuses, axillary
      lymphadenopathy, and cold abscess were included in the study. Medical records of
      the patients presented were reviewed and analyzed. Data was collected regarding
      the patient's name, age and marital and lactational status. Clinical Examinations
      and investigations were carried out by triple assessment i.e. clinical,
      radiological and histological / cytological evaluation. RESULTS: The commonest
      presentation was a solitary breast lump in 30 (60%) patients, breast lump with
      axillary lymphadenopathy in 13 (26%). Four (8%) patients presented with
      generalized breast swelling (edema) with ipsilateral axillary lymphadenopathy.
      Two (4%) presented with breast abscess and axillary lymphadenopathy and one (2%)
      with axillary sinus and breast lump. Upper outer quadrant was most frequently
      involved in 29 (58%) of patients. Thirty-two (64%) cases were secondary to
      tuberculosis in other sites, mostly (40%) from tuberculous axillary
      lymphadenitis. Forty-eight (96%) patients responded well to one year
      antituberculous treatment with complete disappearance of the lumps except 2
      patients who had shrinkage of lump size only, underwent excision of lump.
      CONCLUSION: Solitary lump and enlarged lymph nodes are the commonest presentation
      of mammary tuberculosis. Early diagnosis and treatment is necessary to prevent
      disfigurement of breast. Antituberculous therapy is the treatment of choice.
      Surgery should be reserved for unresponsive lumps.

PMID- 15857599
TI  - Role of imaging in diagnosis of carcinoma of breast.
AB  - Imaging plays an important role in the diagnosis of breast diseases. With the
      advancement in technology new diagnostic modalities have been added in the
      armamentarium of investigation protocols for breast diseases, especially
      carcinoma of breast, which is showing a rising trend in the recent years. This
      includes MRI of breast, color doppler ultrasound, contrast ultrasound, digital
      mammography etc. This article briefly describes the role of imaging in the
      diagnosis of carcinoma breast.

PMID- 15857600
TI  - The ultimate challenge of pregnancy-associated breast carcinoma.
AB  - Pregnancy associated breast carcinoma requires making judicious use of all
      diagnostic modalities and the therapeutic options of surgery, irradiation,
      chemotherapy and hormonal therapy to enhance survival rates. Individualization of
      treatment for each patient is the key to success. The effects on future
      fertility, the time interval before next conception, and whether to breastfeed or
      not are all well-documented. A multidisciplinary coordinated team approach to
      this ultimate challenge of patient care will prove fruitful.

PMID- 15857601
TI  - Dermatofibrosarcoma protuberans.
AB  - Dermatofibrosarcoma protuberans is a rare, locally aggressive, rarely metastatic
      skin tumor which tends to recur. A 45-year-old female presented with
      dermatofibrosarcoma protuberans on her breast as a recurrent nodule after
      excision. Lump was re-excised with wide margins and irradiated. Follow-up was
      done monthly for two years, with no recurrence.

PMID- 15857602
TI  - Pilomatrixoma breast mimicking carcinoma.
AB  - A 50-year-old male with a painless progressively increasing lump of right breast,
      misdiagnosed on fine needle aspiration cytology as carcinoma breast, operated for
      modified radical mastectomy, is presented here. Histopathology of the resected
      specimen revealed pilomatrixoma.

PMID- 15857603
TI  - Skeletal muscle reparative process masquerading round cell neoplasm: word of
      caution.

PMID- 15857604
TI  - Ah receptor- and TCDD-mediated liver tumor promotion: clonal selection and
      expansion of cells evading growth arrest and apoptosis.
AB  - The Ah receptor (AhR) has been characterized as a ligand-activated transcription
      factor which belongs to the bHLH/PAS (basic helix-loop-helix/Per-Arnt-Sim) family
      of chemosensors. Transgenic mouse models revealed adaptive and developmental
      functions of the AhR in the absence of exogenous ligands. Use of persistent
      agonists such as dioxins including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and
      related compounds demonstrated that the AhR mediates a plethora of species- and
      tissue-dependent toxicities, including chloracne, wasting, teratogenicity,
      immunotoxicity, liver tumor promotion and carcinogenicity. However, molecular
      mechanisms underlying most aspects of these toxic responses as well as biological
      functions of the AhR are currently unknown. Previous studies of liver tumor
      promotion in the two-stage hepatocarcinogenesis model indicated that TCDD
      mediates clonal expansion of 'initiated' preneoplastic hepatocytes, identified as
      enzyme-altered foci (EAF) by inhibiting apoptosis and bypassing AhR-mediated
      growth arrest. In contrast, the Ah receptor has been shown in cell models to
      stimulate growth arrest and apoptosis. Possible underlying mechanisms of these
      AhR responses are discussed, including enhanced metabolism of retinoic acid which
      attenuates TGFbeta-mediated apoptosis and interaction of the Ah receptor with the
      hypophosphorylated retinoblastoma tumor suppressor protein. The discrepancy
      between in vivo findings in EAF and AhR functions may be solved by hypothesizing
      that sustained activation of the Ah receptor generates a strong selective
      pressure in liver treated with genotoxic carcinogens leading to selection and
      expansion of clones evading growth arrest and apoptosis. Models are discussed
      which may facilitate verification of this hypothesis.

PMID- 15857605
TI  - 6-Benzylthioinosine analogues as subversive substrate of Toxoplasma gondii
      adenosine kinase: activities and selective toxicities.
AB  - Toxoplasma gondii adenosine kinase (EC.2.7.1.20) is the major route of adenosine
      metabolism in this parasite. The enzyme is significantly more active than any
      other enzyme of the purine salvage in T. gondii and has been established as a
      potential chemotherapeutic target for the treatment of toxoplasmosis. Certain 6
      substituted purine nucleosides act as subversive substrates of T. gondii, but not
      the human, adenosine kinase. Therefore, these compounds are preferentially
      metabolized to their respective nucleotides and become selectively toxic against
      the parasites but not their host. Herein, we report the testing of newly
      synthesized 6-benzylthioinosine analogues with various substituents on the phenyl
      ring of their benzyl group as subversive substrates of T. gondii adenosine
      kinases. The binding affinity of these compounds to T. gondii adenosine kinase
      and their efficacy as antitoxoplasmic agents varied depending on the nature and
      position of the various substituents on the phenyl ring of their benzyl group. p
      Cyano-6-benzylthioinosine and 2,4-dichloro-6-benzylthioinosine were the best
      ligands. In general, analogues with substitution at the para position of the
      phenyl ring were better ligands than those with the same substitutions at the
      meta or ortho position. The better binding of the para-substituted analogues is
      attributed to the combined effect of hydrophobic as well as van der Waals
      interactions. The 6-benzylthioinosine analogues were devoid of host-toxicity but
      all showed selective anti-toxoplasmic effect in cell culture and animal models.
      These results further confirm that toxoplasma adenosine kinase is an excellent
      target for chemotherapy and that 6-substituted purine nucleosides are potential
      selective antitoxoplasmic agents.

PMID- 15857606
TI  - Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human
      leukemia cells.
AB  - It has been shown that proteasome activity is required for cancer cell survival
      and consumption of fruits and vegetables is associated with decreased cancer
      risk. Previously, we reported that grape extract could inhibit proteasome
      activity and induce apoptosis in tumor cells. In this study, we examined the
      flavonoids apigenin, quercetin, kaempferol and myricetin for their proteasome
      inhibitory and apoptosis-inducing abilities in human tumor cells. We report that
      apigenin and quercetin are much more potent than kaempferol and myricetin at: (i)
      inhibiting chymotrypsin-like activity of purified 20S proteasome and of 26S
      proteasome in intact leukemia Jurkat T cells; (ii) accumulating putative
      ubiquitinated forms of two proteasome target proteins, Bax and Inhibitor of
      nuclear factor kappabeta-alpha in Jurkat T cells and (iii) inducing activation of
      caspase-3 and cleavage of poly(ADP-ribose) polymerase in Jurkat T cells. The
      proteasome-inhibitory abilities of these compounds correlated with their
      apoptosis-inducing potencies. Results from computational modeling of the
      potential interactions of these flavonoids to the chymotrypsin site (beta5
      subunit) of the proteasome were consistent with the obtained proteasome
      inhibitory activities. We found that the C(4) carbon may be a site of
      nucleophilic attack by the OH group of N-terminal threonine of proteasomal beta5
      subunit and that the C(3) hydroxyl may alter the ability of these flavonoids to
      inhibit the proteasome. Finally, apigenin neither effectively inhibited the
      proteasome activity nor induced apoptosis in non-transformed human natural killer
      cells. Our results suggested that the proteasome may be a target of these dietary
      flavonoids in human tumor cells and that inhibition of the proteasome by
      flavonoids may be one of the mechanisms responsible for their cancer-preventive
      effects.

PMID- 15857607
TI  - Protection against 2,4,6-trinitrobenzenesulphonic acid-induced colonic
      inflammation in mice by the marine products bolinaquinone and petrosaspongiolide
      M.
AB  - Proinflammatory mediators, namely eicosanoids, reactive oxygen and nitrogen
      species and cytokines, are clearly involved in the pathogenesis of intestinal
      bowel disease. bolinaquinone (BQ) and petrosaspongiolide M (PT), two marine
      products with potent anti-inflammatory action, have been shown to control the
      production of mediators in acute and chronic inflammatory processes. Hence, we
      have tested here the hypothesis that BQ and PT could ameliorate inflammation and
      oxidative stress parameters in 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced
      colitis in Balb/c mice. BQ and PT were given orally in doses of 10 or
      20mg/kg/day. Treatment of the animals with BQ or PT at the highest dose
      significantly protected against TNBS-induced inflammation, as assessed by a
      reduced colonic weight/length ratio and histological scoring. Neutrophilic
      infiltration, interleukin (IL)-1beta and prostaglandin E(2) (PGE(2)) levels, as
      well as cyclooxygenase-2 (COX-2) protein expression were inhibited by both
      compounds. Colonic nitrite and nitrate levels and protein expression of inducible
      nitric oxide synthase (iNOS) were also lower in the treated groups in comparison
      to the TNBS control. BQ and PT reduced nitrotyrosine immunodetection and colonic
      superoxide anion production. Neither compound inhibited the expression of the
      protective protein heme oxygenase-1 (HO-1), although they reduced the extension
      of apoptosis. Our study also indicated that PT could interfere with the
      translocation of p65 into the nucleus, a key step in nuclear factor-kappaB (NF
      kappaB) activation. Altogether, the results suggest that BQ and PT can have
      potential protective actions in intestinal inflammatory diseases.

PMID- 15857608
TI  - Representative aminopeptidases and prolyl endopeptidase from murine macrophages:
      comparative activity levels in resident and elicited cells.
AB  - Macrophages are considered the main effector cells of immune system. Under
      stimulation these cells are known to be activated by a process involving
      morphological, biochemical and functional changes. Since altered peptidase
      activities could be among the factors leading to the differentiation and
      activation of these cells, in the present work seven naphthylamide derivative
      substrates were employed to assess representative aminopeptidase and prolyl
      endopeptidase activities in resident and elicited macrophages of mice. Soluble
      basic aminopeptidase and prolyl endopeptidase and soluble and particulate neutral
      and prolyl dipeptidyl aminopeptidase IV activities were present at measurable
      levels while particulate prolyl endopeptidase and basic aminopeptidase, and
      particulate and soluble cystyl and pyroglutamyl aminopeptidases were not
      detectable. Kinetic parameters, chloride activation and the inhibitory effects of
      puromycin, bestatin, amastatin and diprotin A characterized differential
      properties of these peptidase activities. The observed increment (about 6-17
      fold) of the soluble basic aminopeptidase and prolyl endopeptidase and soluble
      and particulate neutral and prolyl dipeptidyl aminopeptidase IV activities in
      elicited macrophages was particularly relevant, as these might contribute to an
      increased ability of this cell to inactivate several susceptible substrates known
      to be inflammatory and/or immunological mediators.

PMID- 15857609
TI  - Regulation of dense core vesicle release from PC12 cells by interaction between
      the D2 dopamine receptor and calcium-dependent activator protein for secretion
      (CAPS).
AB  - We identified CAPS1 (calcium-dependent activator protein for secretion) as a D2
      dopamine receptor interacting protein (DRIP) in a yeast two-hybrid screen of a
      human brain library using the second intracellular domain of the human D2
      receptor (D2IC2). CAPS1 is an evolutionarily conserved calcium binding protein
      essential for late-stage exocytosis of neurotransmitters from synaptic terminals.
      CAPS1 interaction was confirmed for both the long and short isoforms of the D2
      receptor, but not with any other dopamine receptor subtype. Interaction between
      CAPS1 and the D2 receptor was validated using both pulldown and
      coimmunoprecipitation assays. Deletion mapping localized the D2 receptor binding
      site to a segment located within the C-terminal region of CAPS1 as well CAPS2. In
      PC12 cells, CAPS1 and D2 receptors were found to colocalize within both cytosolic
      and plasma membrane compartments. Overexpression of a truncated D2 receptor
      fragment caused a significant decrease in K(+)-evoked dopamine release from PC12
      cells, whereas no effect on norepinephrine or BDNF release was observed. These
      results suggest that D2 dopamine receptors may modulate vesicle release from
      neuroendocrine cells via direct interaction with components of the exocytotic
      machinery.

PMID- 15857610
TI  - Differential inhibition of cellular glutathione reductase activity by isocyanates
      generated from the antitumor prodrugs Cloretazine and BCNU.
AB  - The antitumor, DNA-alkylating agent 1,3-bis[2-chloroethyl]-2-nitrosourea (BCNU;
      Carmustine), which generates 2-chloroethyl isocyanate upon decomposition in situ,
      inhibits cellular glutathione reductase (GR; EC 1.8.1.7) activity by up to 90% at
      pharmacological doses. GR is susceptible to attack from exogenous electrophiles,
      particularly carbamoylation from alkyl isocyanates, rendering the enzyme unable
      to catalyze the reduction of oxidized glutathione. Evidence implicates inhibition
      of GR as a cause of the pulmonary toxicity often seen in high-dose BCNU-treated
      animals and human cancer patients. Herein we demonstrate that the prodrug
      Cloretazine (1,2-bis[methylsulfonyl]-1-[2-chloroethyl]-2
      [(methylamino)carbonyl]hydrazine; VNP40101M), which yields methyl isocyanate and
      chloroethylating species upon activation, did not produce similar inhibition of
      cellular GR activity, despite BCNU and Cloretazine being equally potent
      inhibitors of purified human GR (IC(50) values of 55.5 microM and 54.6 microM,
      respectively). Human erythrocytes, following exposure to 50 microM BCNU for 1h at
      37 degrees C, had an 84% decrease in GR activity, whereas 50 microM Cloretazine
      caused less than 1% inhibition under the same conditions. Similar results were
      found using L1210 murine leukemia cells. The disparity between these compounds
      remained when cells were lysed prior to drug exposure and were partially
      recapitulated using purified enzyme when 1mM reduced glutathione was included
      during the drug exposure. The superior antineoplastic potential of Cloretazine
      compared to BCNU in animal models could be attributed in part to the contribution
      of the methyl isocyanate, which is synergistic with the co-generated cytotoxic
      alkylating species, while at the same time unable to significantly inhibit
      cellular GR.

PMID- 15857611
TI  - Protective effect of FK506 against apoptosis of SH-SY5Y cells correlates with
      regulation of the serum inducible kinase gene.
AB  - Recently, we established an in vitro model of apoptosis induced by exposure of
      neuroblastoma SH-SY5Y cells to thapsigargin, an endoplasmic reticular calcium
      ATPase inhibitor, and demonstrated that FK506 (tacrolimus) protected against
      apoptosis. The purpose of this paper was to investigate a possible correlation
      between the protective effect of FK506 against apoptosis and the regulation of
      the serum inducible kinase (SNK) and fibroblast growth factor inducible kinase
      (FNK) genes-which are polo-like kinases expressed abundantly in the brain by
      FK506. Thapsigargin increased the mRNA level of SNK and FNK in SH-SY5Y cells.
      FK506 inhibited the increase in SNK mRNA but not FNK mRNA. Deletion analysis of
      the SNK promoter showed that the promoter site, which was regulated by
      thapsigargin and FK506 in a calcineurin-dependent manner, is a cAMP response
      element (CRE)/activating transcription factor (ATF)-like element located 84 base
      pairs (bp) proximal to the transcriptional initiation site. Although
      transcription of the SNK gene was also regulated by tunicamycin, etoposide, or
      staurosporine, FK506 did not show any effects on these regulations. We recently
      reported that FK506 did not protect against apoptosis induced by these agents.
      These results indicate that the induction of SNK mRNA by thapsigargin in SH-SY5Y
      cells is regulated by FK506 via an inhibition of calcineurin at the
      transcriptional stage, and the transcriptional regulation of the SNK gene by
      FK506 was well correlated with the protective effect of the compound against
      apoptosis. Thus, transcriptional regulation of the SNK gene may be a biological
      marker for analysis of apoptosis of SH-SY5Y cells.

PMID- 15857612
TI  - Ca2+ sensitization and the regulation of contractility in rat anococcygeus and
      retractor penis muscle.
AB  - Stimulation of the RhoA/Rho-kinase (ROK) signaling represents a key step in the
      maintenance of agonist-induced contraction of smooth muscle. We aimed to
      demonstrate Ca(2+) sensitization in rat anococcygeus and retractor penis muscles
      and to identify the molecular expression of major components of this pathway.
      Both anococcygeus and retractor penis showed a similar expression of RhoA,
      ROKalpha, and ROKbeta at the protein level as well as the mRNA for RhoGEFs.
      Cumulative addition of the ROK inhibitors H-1152 (0.001-3 microM), Y-27632 (0.01
      30 microM) or HA-1077 (0.01-30 microM) caused sustained relaxations of
      precontracted smooth muscle strips. Ca(2+) sensitization induced by
      phenylephrine, norepinephrine and carbachol was markedly antagonized by all three
      ROK inhibitors. In addition, the contractile response to KCl-induced
      depolarization was highly sensitive to these ROK inhibitors. H-1152 was
      approximately 8-20 more potent than Y-27632 and HA-1077 to inhibit contraction.
      Electrical field stimulation (EFS, 1-32 Hz) caused transient contractions in both
      anococcygeus and retractor penis muscle, which were blocked by tetrodotoxin (1
      microM), phentolamine (1 microM) or bretylium tosylate (30 microM). Similarly, H
      1152 (0.1-1 microM), Y-27632 (1-10 microM) or HA-1077 (1-10 microM) significantly
      reduced EFS-evoked contractions in a concentration-dependent manner. The results
      indicate that the RhoA/ROK-mediated Ca(2+) sensitization pathway is expressed in
      anococcygeus and retractor penis muscles and enhances contractions produced by
      receptor-dependent and independent mechanisms.

PMID- 15857613
TI  - Stimulation of neuropeptide Y-mediated calcium responses in human SMS-KAN
      neuroblastoma cells endogenously expressing Y2 receptors by co-expression of
      chimeric G proteins.
AB  - Human SMS-KAN neuroblastoma cells endogenously express the neuropeptide Y (NPY)
      type 2 (Y(2)) receptor. Although ligand binding and GTPgammaS binding studies
      supported high functional Y(2) receptor expression, only weak coupling to the
      natural second messenger cyclic AMP was observed. The main reason was the low
      responsiveness of SMS-KAN cells to forskolin, a direct activator of adenylyl
      cyclases. In order to obtain a cell-based functional assay for the Y(2) receptor
      in SMS-KAN cells, the transient calcium (Ca(2+)) mobilization assay in the
      fluorimetric imaging plate reader (FLIPR) format was established by stably
      expressing a chimeric G protein Gq(i9). This manipulation resulted in robust
      mobilization of Ca(2+) after challenge with various NPY-related agonists in a 384
      well format. The sensitivity of the FLIPR readout was in the low nanomolar range
      for NPY agonists and comparable to that of the recombinant Y(2) receptor. The
      selective Y(2) antagonist BIIE0246 competitively inhibited NPY-mediated Ca(2+)
      transients in SMS-KAN/Gq(i9) cells with a pA(2) value of 7.39+/-0.1. This is the
      first evidence that an endogenously expressed G protein-coupled receptor couples
      to an overexpressed chimeric G protein, thereby functionally responding in the
      FLIPR readout.

PMID- 15857614
TI  - Histone deacetylases inhibition and tumor cells cytotoxicity by CNS-active VPA
      constitutional isomers and derivatives.
AB  - The tumor cells toxicity of the antiepileptic drug valproic acid (VPA) has been
      associated with the inhibition of histone deacetylases (HDACs). We have assessed,
      in comparison to VPA, the HDACs inhibition and tumor cells cytotoxicities of CNS
      active VPA's constitutional isomers, valnoctic acid (VCA), propylisopropylacetic
      acid (PIA), diisopropylacetic acid (DIA), VPA's cyclopropyl analogue 2,2,3,3
      tetramethylcyclopropanecarboxylic acid (TMCA) and VPA's metabolites, 2-ene-VPA
      and 4-ene-VPA, all possessing, as does VPA, eight carbon atoms in their
      structures. The aim was to define structural components of the VPA molecule that
      are involved in HDACs inhibition and tumor cells cytotoxicity. HDACs inhibition
      by the above-mentioned compounds was estimated using an acetylated lysine
      substrate and HeLa nuclear extract as a HDACs source. SW620 cells were used for
      assessing HDACs inhibition in vivo. The cytotoxicity of these compounds was
      assessed in SW620 and 1106mel cells. HDAC inhibition potency was the highest for
      VPA and 4-ene-VPA (IC(50)=1.5mM each). 2-Ene-VPA inhibited HDACs with
      IC(50)=2.8mM. IC(50) values of the other tested compounds for HDACs inhibition
      were higher than 5mM, 4-ene-VPA and VPA induced histone hyperacetylation in SW620
      cells. 4-Ene-VPA and VPA at 2mM each were also most potent in reducing cell
      viability, to 59+/-2.0% and 67.3+/-5.4%, respectively, compared to control. VCA,
      PIA, DIA, TMCA, 2-ene-VPA and valpromide (VPD) did not reduce viability to less
      than 80%. All tested compounds did not significantly affect the cell cycle of
      SW620 cells. In conclusion, in comparison to the VPA derivatives and
      constitutional isomers tested in this study, VPA had the optimal chemical
      structure in terms of HDACs inhibition and tumor cells cytotoxicity.

PMID- 15857615
TI  - Binding of [3H]MK-801 in subcellular fractions of Schistosoma mansoni: evidence
      for interaction with nicotinic receptors.
AB  - Several studies have suggested that l-glutamate is a putative neurotransmitter in
      Schistosoma mansoni. Recently, we detected the presence of low-affinity binding
      sites for [(3)H]kainic acid in the heterogeneous (P(1)) subcellular fraction of
      S. mansoni. In an attempt to characterize N-methyl-d-aspartate (NMDA) receptors
      in this worm, we performed binding assays with [(3)H]MK-801, a NMDA non
      competitive antagonist, in the P(1) fraction of adult S. mansoni. In competition
      experiments, MK-801 (IC(50) approximately 200 microM) and ketamine (IC(50)
      approximately 500 microM) exhibited a low affinity for the sites labeled with
      [(3)H]MK-801. Along with the lack of modulation of this binding by glutamatergic
      agonists and antagonists and the absence of stereoselectivity for MK-801 isomers,
      these results suggest that [(3)H]MK-801 could label a site different from the
      classical NMDA receptor in S. mansoni. Based on the evidences that MK-801
      interacts with mammalian muscle and central nervous system nicotinic receptors as
      a low-affinity noncompetitive antagonist, we have investigated the effects of MK
      801 on the nicotine-induced flaccid paralysis of the worm, in vivo. The motility
      of S. mansoni was quantified by image analysis through a measure of displacement
      of the worm's extremities. In the presence of (-)-nicotine (10-100 microM), we
      observed an immediate paralysis of the worms, that was inhibited by 1mM MK-801.
      Besides nicotine, choline (10-50mM) was also able to inhibit the worm's motility.
      As a conclusion, we suggest that [(3)H]MK-801 binds to nicotinic receptors, and
      not NMDA receptors, in subcellular fractions of S. mansoni.

PMID- 15857616
TI  - Inhibition of thymidine phosphorylase (PD-ECGF) from SD-lymphoma by
      phosphonomethoxyalkyl thymines.
AB  - A series of thymine phosphonomethoxyalkyl derivatives were evaluated for their
      ability to inhibit thymidine phosphorylase (dThdPase) purified from rat
      spontaneous T-cell lymphoma. A kinetic study of thymidine phosphorolysis
      catalyzed by dThdPase was performed with thymidine and/or inorganic phosphate as
      substrates. Data show that the substantial inhibitory effect of these acyclic
      nucleotide analogues is decreasing in the order of (R)-FPMPT>(S)-FPMPT>or=(R)
      HPMPT>(S)-PMPT>(S)-HPMPT>PMET>or=(R)-PMPT. The inhibitory potency
      (K(i)/(dThd)K(m)) of the most efficient inhibitors from this series against T
      cell lymphoma enzyme is 0.0026 for (R)-FPMPT and 0.0048 for (S)-FPMPT. The
      studied compounds do not inhibit Escherichia coli and human enzyme and possess
      lower inhibitory potency against rat liver thymidine phosphorylase.

PMID- 15857617
TI  - Inhibition of human liver catechol-O-methyltransferase by tea catechins and their
      metabolites: structure-activity relationship and molecular-modeling studies.
AB  - (-)-Epigallocatechin-3-gallate (EGCG) is the major polyphenol present in green
      tea. We previously demonstrated that EGCG was both a substrate and potent
      inhibitor of human liver cytosolic catechol-O-methyltransferease (COMT). We now
      report the structure-activity relationship for the inhibition of COMT-catalyzed O
      methylation of catecholestrogens in human liver cytosol by tea catechins and some
      of their metabolites. The most potent inhibitors were catechins with a galloyl
      type D-ring, including EGCG (IC(50)=0.07 microM), 4''-O-methyl-EGCG (IC(50)=0.10
      microM), 4',4''-di-O-methyl-EGCG (4',4''-DiMeEGCG) (IC(50)=0.15 microM), and (-)
      epicatechin-3-gallate (ECG) (IC(50)=0.20 microM). Catechins without the D-ring
      showed two to three orders of magnitude less inhibitory potency. Enzyme kinetic
      analyses revealed that EGCG behaved as a mixed inhibitor, whereas 4',4''-di-O
      methyl-EGCG exhibited competitive kinetics for the S-adenosylmethionine (SAM),
      and noncompetitive kinetics for the catechol binding site. These compounds may
      represent a new type of COMT inhibitor. In silico molecular-modeling studies
      using a homology model of human COMT were conducted to aid in the understanding
      the catalytic and inhibitory mechanisms. Either D-ring or B-ring of EGCG could be
      accommodated to the substrate binding pocket of human COMT. However, the close
      proximity (2.6A) of 4''-OH to the critical residue Lys144, the higher acidity of
      the hydroxyl groups of the D-ring, and the hydrophobic interactions between the D
      ring and residues in the binding pocket greatly facilitated the interaction of
      the D-ring with the enzyme, and resulted in increased inhibitory potency. These
      results provide mechanistic insight into the inhibition of COMT by commonly
      consumed tea catechins.

PMID- 15857618
TI  - Electrochemical characterisation of the human cytochrome P450 CYP2C9.
AB  - The electrochemistry of human cytochrome P4502C9 (CYP2C9) was characterised using
      purified His-tagged enzyme. The His-tagged enzyme was shown to have similar
      functional characteristics to native CYP2C9 heterologously expressed in
      Escherichia coli and to the CYP2C9 activity of human liver microsomes. Evidence
      was observed for a reversible one-electron transfer between the P450 heme and the
      electrode. Both pH and ionic strength influenced the electrochemical behaviour of
      CYP2C9. A range of substrates was investigated to determine the effect of the
      heme-substrate interaction on CYP2C9 redox potential. In the absence of oxygen,
      tolbutamide, diclofenac, warfarin and sulfaphenazole did not alter the redox
      potential of the iron heme. In contrast, torsemide, carbon monoxide and oxygen
      led to an anodic shift in redox potential. These results suggest alternative
      mechanisms by which CYP2C9 (and by inference other P450 enzymes) may alter redox
      potential to facilitate electron delivery from physiological donors.

PMID- 15857619
TI  - Comparison of the effects of diazepam, the CRF1 antagonist CP-154,526 and the
      group II mGlu receptor agonist LY379268 on stress-evoked extracellular
      norepinephrine levels.
AB  - The present study used an elevated platform procedure to investigate the effects
      of diazepam, a CRF1 antagonist CP-154,526 and a group II mGlu2/3 receptor agonist
      LY379268 on stress-evoked increase in extracellular norepinephrine (NE).
      Pretreatment with either diazepam (1 mg/kg, i.p.), CP-154,526 (20 mg/kg, i.p.) or
      LY379268 (1, 3 and 10 mg/kg, p.o.) significantly reduced platform stress-evoked
      NE. Interestingly, at the highest dose tested (10 mg/kg) LY379268 caused a marked
      increase in baseline NE levels. We tested whether this effect would diminish
      after repeated dosing. In contrast to acute administration, a challenge injection
      of LY379268 after repeated dosing (10 mg/kg x days) did not alter basal NE.
      Importantly, although less effective, LY379268 still significantly reduced stress
      evoked NE. We further show that this increase in basal NE may involve mGlu2/3
      receptor regulation of the GABAergic system. To this end, administration of the
      GABAB agonist, baclofen (4 mg/kg, i.p.), 2 h after dosing with LY379268, reversed
      the increase in baseline NE. These data suggest that, like diazepam and CP
      154,526, group II mGlu2/3 receptor agonists can attenuate stress-evoked increase
      in extracellular NE in the rat prefrontal cortex. In addition they reveal a
      'stress-like' increase in NE after high doses of LY379268 which may reflect mGlu3
      receptor modulation of GABAergic transmission.

PMID- 15857620
TI  - Long-term potentiation persists in an occult state following mGluR-dependent
      depotentiation.
AB  - Depotentiation, the reversal of long-term potentiation (LTP), can be induced by
      activation of metabotropic glutamate receptors (mGluRs) or NMDA receptors
      (NMDARs). Although NMDAR-dependent depotentiation is due to a protein phosphatase
      dependent erasure of LTP, the notion that mGluR-dependent depotentiation also
      involves LTP erasure is controversial. To address this issue we used
      electrophysiological and biochemical approaches to investigate mGluR-dependent
      depotentiation in hippocampal slices. Activating group I mGluRs with (R,S)-3,5
      dihydroxyphenylglycine (DHPG) induced robust depotentiation in both the CA1 and
      CA3 regions of hippocampal slices. Western immunoblotting of samples prepared
      from DHPG-treated slices revealed, however, that activation of group I mGluRs
      causes a transient increase in phosphorylation of AMPA receptor GluR1 subunits at
      sites crucial for LTP and under some conditions causes persistent activation of
      alphaCamKII. The paradoxical ability of DHPG to induce depotentiation while at
      the same time activating signaling pathways involved in LTP suggests that LTP
      might not be erased by mGluR-dependent depotentiation. Consistent with this, DHPG
      induced depotentiation did not restore the ability of high-frequency stimulation
      to induce LTP at synapses that had previously undergone saturating levels of LTP.
      In addition, blocking the expression of DHPG-induced LTD revealed hidden LTP at
      depotentiated synapses. Our results indicate that LTP and mGluR-dependent LTD can
      co-exist at excitatory synapses.

PMID- 15857621
TI  - ATP hydrolysis is required for the rapid regulation of AMPA receptors during
      basal synaptic transmission and long-term synaptic plasticity.
AB  - ATP hydrolysis is critical for many cellular processes; however, the acute
      requirement for ATP hydrolysis in synaptic transmission and plasticity in neurons
      is unknown. Here we studied the effects of postsynaptically applying the non
      hydrolyzable ATP analogue adenosine 5'-[beta,gamma-methylene]triphosphate (AMP
      PCP) into hippocampal CA1 pyramidal cells in hippocampal slices. The effects of
      this manipulation were investigated on basal transmission and on two forms of
      long-term synaptic plasticity, long-term potentiation (LTP) and long-term
      depression (LTD). AMP-PCP caused an increase in basal AMPA receptor (AMPAR)
      mediated transmission, which occurred rapidly within minutes of infusing the
      drug. This effect was selective for AMPARs, since pharmacologically isolated
      NMDAR-mediated synaptic currents did not exhibit this run up. In two-pathway
      experiments infusion of AMP-PCP blocked the induction of both LTD and LTP. These
      findings show an acute and selective role for ATP hydrolysis in regulating AMPAR
      function both during basal transmission and long-term synaptic plasticity. Recent
      evidence indicates that AMPARs are selectively and acutely regulated by the
      ATPase N-ethylmaleimide-sensitive factor (NSF), which forms part of a multi
      protein complex with AMPARs. Our data are consistent with the idea that such a
      mechanism that can acutely bi-directionally regulate AMPAR function at synapses
      and requires ATP hydrolysis is necessary for rapid activity-dependent changes in
      synaptic strength.

PMID- 15857622
TI  - GABAB receptor antagonist SGS742 improves spatial memory and reduces protein
      binding to the cAMP response element (CRE) in the hippocampus.
AB  - Memory storage in the brain requires protein synthesis initiated through
      signaling pathways that control transcription. Such mechanisms are under active
      investigation for therapies in disorders involving cognitive dysfunction. Long
      term memory can be improved by inhibiting activation or reducing expression of
      transcription factors such as ATF4/CREB2 and some C/EBP family members which
      appear to serve as memory suppressors. Here, we provide evidence that GABAB
      receptor antagonists may enhance cognition, at least in part, by this mechanism.
      We tested a GABAB receptor antagonist, SGS742 (CGP36742), on hippocampal
      dependent memory and hippocampal nuclear CRE-binding activity in rats. As a
      result, acute in vivo administration of SGS742 both improved memory and reduced
      total hippocampal CRE-binding activity of which a large proportion in the basal
      state could be immunoneutralized with CREB2 antibodies. Consistent with its
      activity on information storage mechanisms, acute SGS742 effectively improved
      long-term memory in retrograde protocols, in which drug was given at times when
      memory formation can be interrupted by blocking new protein production. In
      conclusion, GABAB antagonists may provide a pharmacological therapy for cognitive
      impairment, sharing mechanistic features with genetic approaches to reduce CREB2
      activity and to augment long-term memory.

PMID- 15857623
TI  - Acute or repeated cocaine administration generates reactive oxygen species and
      induces antioxidant enzyme activity in dopaminergic rat brain structures.
AB  - Either a single (acute) or repeated daily (chronic) injections (1 injection/day)
      of 20 mg/kg cocaine for 10 days to rats was found to increase reactive oxygen
      species production in two dopaminergic brain structures, the frontal cortex and
      the striatum. We found that the mitochondrial genome was down-regulated after
      acute cocaine injection. Hydroperoxide and lipid peroxide generation was
      correlated with an increase in mitochondrial hydrogen peroxide generation and
      with a reduced functioning of mitochondrial complex I in response to cocaine. As
      judged from the measurement of caspase-3 activity and TUNEL labeling, neither
      acute nor chronic cocaine treatment has been found to induce apoptosis in any of
      the structures examined. This differs dramatically from what has been described
      for methamphetamine. Cocaine-induced radical formation was accompanied by the
      induction of the antioxidant enzymes superoxide dismutase and glutathione
      peroxidase, after both acute and chronic cocaine treatment. In addition,
      proteasome chymotrypsin-like activity was enhanced following a single cocaine
      injection in both cortex and striatum. It is proposed that the compensatory
      mechanisms to oxidative stress occurring in response to cocaine were effective in
      scavenging reactive oxygen species and in preventing subsequent cellular damage,
      thus explaining why no significant cell death was found in these brain
      structures.

PMID- 15857624
TI  - Pharmacological and histological characterisation of nicotine-kindled seizures in
      mice.
AB  - The present study reports that it is possible to induce kindling by repeated
      injections of nicotine. The newly characterised nicotine-kindling model was
      compared with that of pentylenetetrazole (PTZ) kindling. Mice were kindled by
      repeated injection of PTZ (37 mg/kg), or nicotine (2.3 mg/kg), and the effect of
      the anti-epileptic drugs (AED) levetiracetam (LEV), tiagabine (TGB) and phenytoin
      (PHT) on seizures in kindled and naive mice were investigated. C-Fos
      immunoreactivity (Fos IR) was used to investigate differences in neuronal
      activity pattern between PTZ-, nicotine kindled and naive animals. PTZ kindled
      animals mainly showed increased Fos IR in limbic regions, whereas Fos IR in
      nicotine kindled animals was increased in the entorhinal cortex, medial habenula
      and the compact part of substantia nigra. Fully kindled PTZ-induced seizures were
      inhibited by LEV (ED50=13.6+/-7.8 mg/kg), TGB (ED50=0.3+/-0.04 mg/kg) but not PHT
      (ED50>40 mg/kg) whereas fully kindled nicotine-induced seizures were inhibited by
      LEV (ED50=1.4+/-0.4 mg/kg), TGB (ED50=0.3+/-0.06 mg/kg) and PHT (ED50=9.2+/-2.4
      mg/kg). These differences in efficacy of AEDs were not due to changes in plasma
      levels in the various models. In conclusion, repeated administration of nicotine
      can induce a kindling-like phenomenon and the model showed significantly
      different Fos IR pattern and pharmacology to that of PTZ kindling.

PMID- 15857625
TI  - Studies of ATP-sensitive potassium channels on 6-hydroxydopamine and haloperidol
      rat models of Parkinson's disease: implications for treating Parkinson's disease?
AB  - In the present study, we first investigated the effects of unilateral 6
      hydroxydopamine (6-OHDA) lesioning of the substantia nigra pars compacta (SNc) on
      the expression of subunits of ATP-sensitive potassium channels (KATP channels) in
      the prefrontal cortex (PFC), striatum and hippocampus of adult rats by utilizing
      semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and
      immunohistochemistry techniques. The results show that Kir6.2 and SUR2 expression
      in the PFC, Kir6.1, Kir6.2 and SUR1 expression in the striatum, and Kir6.1 and
      Kir6.2 expression in the hippocampus of injured side increased significantly
      after unilateral 6-OHDA lesioning of the SNc in rats. Afterward, we studied the
      effects of iptakalim (Ipt), a novel ATP-sensitive potassium channel opener (KCO),
      on parkinsonian symptoms, which were induced by acute injection of haloperidol.
      The results indicate that intraperitoneal injection of Ipt (0.125 mg/kg, 0.25
      mg/kg or 0.5 mg/kg) partially alleviated haloperidol-induced catalepsy and
      hypolocomotion. Even though the observed effects (0.5 mg/kg) are better than
      those of l-3,4-dihydroxyphenylalanine (L-DOPA) (100 mg/kg), Ipt (0.25 mg/kg)
      failed to enhance the anti-parkinsonian actions of L-DOPA (100 mg/kg). Our
      results suggest that KATP channels might be involved in the pathogenesis of
      Parkinson's disease (PD) induced in an animal model and conceptually support the
      idea that KATP channels may be new therapeutic targets for PD.

PMID- 15857626
TI  - Beneficial effects of vitamin C and vitamin E on reserpine-induced oral
      dyskinesia in rats: critical role of striatal catalase activity.
AB  - Oral dyskinesias are implicated in a series of neuropathologies and have been
      associated to an increase in oxidative stress. Several antioxidants, including
      vitamin E, decrease reserpine-induced oral dyskinesia (OD) in rodents and we have
      described a protective role of striatal catalase against the development of OD.
      The aim of this study was to verify the effects of vitamin C alone or in
      combination with vitamin E on reserpine-induced OD as well as to determine a
      possible role of catalase in the antidyskinetic property of these vitamins.
      Different doses of vitamin C attenuated reserpine-induced increase in OD. A
      similar treatment with an effective dose of vitamin C concomitant to an effective
      dose of vitamin E potentiated the antidyskinetic effect of both vitamins when
      administered alone. The administration of these vitamins alone produced an
      increase in striatal catalase activity that likewise was potentiated by their
      combined administration. In addition, the antidyskinetic property of vitamin E
      and vitamin C was abolished by a concomitant treatment with the catalase
      inhibitor aminotriazole. These results indicate a beneficial effect of these
      vitamins and reinforce the critical role of striatal catalase against the
      development of oral dyskinesias.

PMID- 15857628
TI  - Comparison of the effects of anticonvulsant drugs with diverse mechanisms of
      action in the formalin test in rats.
AB  - The purpose of the present studies was to compare anticonvulsant drugs with
      diverse mechanisms of action in a persistent pain model, the formalin test. In
      addition, the anticonvulsant effects of the compounds were determined in the
      threshold electroshock tonic seizure test and the 6-Hz limbic seizure test. The
      effects of the compounds were also determined on locomotor activity.
      Carbamazepine, oxcarbazepine, lamotrigine, gabapentin and ethosuximide all
      produced statistically significant analgesic effects in the formalin test whereas
      phenytoin, topiramate, zonisamide, phenobarbital, tiagabine, valproate and
      levetiracetam did not. All compounds were anticonvulsant. In addition, morphine
      and phenobarbital increased locomotor activity while ethosuximide had no effect
      and all other compounds decreased locomotor activity. For those compounds that
      were analgesic, the doses required to produce analgesia were larger in magnitude
      than the anticonvulsant ED50 values in the threshold electroshock and 6-Hz tests,
      as well as larger than doses that altered locomotor activity. The present results
      demonstrate that the anticonvulsant and analgesic effects of clinically used
      antiepileptic drugs do not necessarily correlate and therefore suggest that the
      anticonvulsant and analgesic efficacy of these drugs may be due to different
      pharmacologic mechanisms.

PMID- 15857627
TI  - Determination of guinea-pig cortical gamma-secretase activity ex vivo following
      the systemic administration of a gamma-secretase inhibitor.
AB  - (2S)-2-{[(3,5-Diflurophenyl)acetyl]amino}-N-[(3S)-1-methyl-2-oxo-5-phenyl-2,3
      dihydro-1H-1,4-benzodiazepin-3-yl]propanamide (compound E) is a gamma-secretase
      inhibitor capable of reducing amyloid beta-peptide (1-40) and amyloid beta
      peptide (1-42) levels. In this study we investigated the effect of in vivo
      administration of compound E on guinea-pig plasma, CSF and cortical amyloid beta
      peptide (1-40) concentration. Using repeated sampling of CSF, compound E (30
      mg/kg p.o.) was shown to cause a time-dependent decrease in CSF amyloid beta
      peptide (1-40) levels, which was maximal at 3 h (70% inhibition), compared to
      baseline controls. After 3 h administration, compound E (3, 10 and 30 mg/kg
      p.o.), reduced plasma, CSF and DEA-extracted cortical amyloid beta-peptide (1-40)
      levels by 95, 97 and 99%; 26, 48 and 78%; 32, 33, and 47%, respectively, compared
      to vehicle control values. In the same animals, compound E (3, 10 and 30 mg/kg
      p.o.) inhibited cortical gamma-secretase activity, determined ex vivo using the
      recombinant substrate C100Flag, by 40, 71 and 79% of controls, respectively.
      These data demonstrate the value of determining not only the extent by which
      systemic administration of a gamma-secretase inhibitor reduces amyloid beta
      peptide, but also the inhibition of brain gamma-secretase activity, as a more
      direct estimate of enzyme occupancy.

PMID- 15857629
TI  - Mechanisms involved in the antinociception caused by agmatine in mice.
AB  - The present study examined the antinociceptive effects of agmatine in chemical
      behavioural models of pain. Agmatine (1-30 mg/kg), given by i.p. route, 30 min
      earlier, produced dose-dependent inhibition of acetic acid-induced visceral pain,
      with mean ID50 value of 5.6 mg/kg. Given orally, 60 min earlier, agmatine (10-300
      mg/kg) also produced dose-related inhibition of the visceral pain caused by
      acetic acid, with mean ID50 value of 147.3 mg/kg. Agmatine (3-100 mg/kg, i.p.)
      also caused significant and dose-dependent inhibition of capsaicin- and glutamate
      induced pain, with mean ID50 values of 43.7 and 19.5 mg/kg, respectively.
      Moreover, agmatine (1-100 mg/kg, i.p.) caused marked inhibition of both phases of
      formalin-induced pain, with mean ID50 values for the neurogenic and the
      inflammatory phases of 13.7 and 5.6 mg/kg, respectively. The antinociception
      caused by agmatine in the acetic acid test was significantly attenuated by i.p.
      treatment of mice with L-arginine (precursor of nitric oxide, 600 mg/kg),
      naloxone (opioid receptor antagonist, 1 mg/kg), p-chlorophenylalanine methyl
      ester (PCPA, an inhibitor of serotonin synthesis, 100 mg/kg once a day for 4
      consecutive days), ketanserin (a 5-HT2A receptor antagonist, 0.3 mg/kg),
      ondansetron (a 5-HT3 receptor antagonist, 0.5 mg/kg), yohimbine (an alpha2
      adrenoceptor antagonist, 0.15 mg/kg) or by efaroxan (an I1 imidazoline/alpha2
      adrenoceptor antagonist, 1 mg/kg). In contrast, agmatine antinociception was not
      affected by i.p. treatment of animals with pindolol (a 5-HT1A/1B receptor
      antagonist, 1 mg/kg) or idazoxan (an I2 imidazoline/alpha2-adrenoceptor
      antagonist, 3 mg/kg). Likewise, the antinociception caused by agmatine was not
      affected by neonatal pre-treatment with capsaicin. Together, these results
      indicate that agmatine produces dose-related antinociception in several models of
      chemical pain through mechanisms that involve an interaction with opioid,
      serotonergic (i.e., through 5-HT2A and 5-HT3 receptors) and nitrergic systems, as
      well as via an interaction with alpha2-adrenoceptors and imidazoline I1
      receptors.

PMID- 15857630
TI  - Zaltoprofen inhibits bradykinin-induced responses by blocking the activation of
      second messenger signaling cascades in rat dorsal root ganglion cells.
AB  - Bradykinin interacts with the bradykinin B2 receptor on dorsal root ganglion
      (DRG) neurons, setting off a series of reactions inside the cells that ultimately
      make the vanilloid receptor 1 more sensitive to a normal stimulus by activating
      various enzymes coupled with second messenger signaling cascades. Zaltoprofen, a
      propionic acid derivative non-steroidal anti-inflammatory drug (NSAID), was
      proved to inhibit bradykinin-induced pain responses in vivo experimental systems
      more potently than indomethacin or other NSAIDs, but the molecular mechanisms
      underlying its action are not yet fully understood. Currently it appears unlikely
      that zaltoprofen binds to specific sites on the protein of the bradykinin B2
      receptor, hence we have examined the effect of zaltoprofen on bradykinin-induced
      responses of adult DRG neurons to investigate possible interaction sites.
      Compared with several other NSAIDs, such as indomethacin, loxoprofen and
      diclofenac, zaltoprofen most potently inhibits bradykinin-enhancement of
      capsaicin-induced 45Ca2+ uptake into DRG neurons. Zaltoprofen also significantly
      inhibits bradykinin-induced 12-lipoxygenase (12-LOX) activity and the slow
      bradykinin-induced onset of substance P release from DRG neurons. These data
      indicate zaltoprofen may produce its analgesic effects through the inhibition of
      bradykinin B2 receptor-mediated bradykinin responses of not only cyclooxygenases
      (COXs) but also bradykinin induced 12-LOX inhibitors.

PMID- 15857631
TI  - Establishment of robust functional assays for the characterization of
      neuropeptide Y (NPY) receptors: identification of 3-(5-benzoyl-thiazol-2-ylamino)
      benzonitrile as selective NPY type 5 receptor antagonist.
AB  - The human Neuropeptide Y (NPY) receptors 1 (hY1), 2 (hY2), 4 (hY4), and the mouse
      type 5 (mY5) receptor were expressed in human embryonic kidney 293 (HEK293)
      cells. The receptors bound a radioiodinated NPY ligand with high affinity and
      various NPY analogs competed for binding in a receptor selective-manner.
      Similarly, cAMP-inhibition and GTPgammaS binding assays were established. The
      four NPY receptors were further tested in the fluorimetric imaging plate reader
      (FLIPR) format, a cellular high-throughput assay, in the absence and presence of
      chimeric G proteins, Gqo5, Gqi5 and Gqi9. The receptors stimulated transient
      calcium release only in the presence of chimeric G proteins. While hY1, hY2 and
      hY4 receptors coupled to Gqo5, Gqi5 and Gqi9, the mY5 receptor stimulated
      transient calcium release only when co-expressed with Gqi9. Using an in silico
      screening approach we identified a small molecule 3-(5-benzoyl-thiazol-2-ylamino)
      benzonitrile (compound 1), which bound to the mY5 receptor with high affinity
      (Ki=32.1+/-1.8 nM), competitively antagonized NPY-mediated GTPgammaS binding and
      calcium stimulation with high potency, and had no affinity for other NPY
      receptors. These data show that NPY receptors can be functionally coupled to the
      FLIPR readout, allowing for high throughput compound testing and identification
      of novel molecules.

PMID- 15857632
TI  - Mechanisms of Na+ and Ca2+ influx into respiratory neurons during hypoxia.
AB  - Changes in intracellular Na+ and Ca2+ in inspiratory neurons of neonatal mice
      were examined by using ion-selective fluorescent indicator dyes SBFI and fura-2,
      respectively. Both [Na+]i and [Ca2+]i signals showed rhythmic elevations,
      correlating with the inspiratory motor output. Brief (2-3 min) hypoxia, induced
      initial potentiation of rhythmic transients followed by their depression. During
      hypoxia, the basal [Na+]i and [Ca2+]i levels slowly increased, reflecting
      development of an inward current (Im). By antagonizing specific mechanisms of Na+
      and Ca2+ transport we found that increases in [Na+]i, [Ca2+]i and Im due to
      hypoxia are suppressed by CNQX, nifedipine, riluzole and flufenamic acid,
      indicating contribution of AMPA/kainate receptors, persistent Na+ channels, L
      type Ca2+ channels and Ca2+-sensitive non-selective cationic channels,
      respectively. The blockers decreased also the amplitude of the inspiratory
      bursts. Modification of mitochondrial properties with FCCP and cyclosporine A
      decreased [Ca2+]i elevations due to hypoxia by about 25%. After depletion of
      internal Ca2+ stores with thapsigargin, the blockade of NMDA receptors, Na+/K+
      pump, Na+/H+ and Na+/Ca2+ exchange, the hypoxic response was not changed. We
      conclude that slow [Na+]i and [Ca2+]i increases in inspiratory neurons during
      hypoxia are caused by Na+ and Ca2+ entry due to combined activation of persistent
      Na+ and L-type Ca2+ channels and AMPA/kainate receptors.

PMID- 15857633
TI  - Anaerobic biodegradability and methanogenic toxicity of key constituents in
      copper chemical mechanical planarization effluents of the semiconductor industry.
AB  - Copper chemical mechanical planarization (CMP) effluents can account for 30-40%
      of the water discharge in semiconductor manufacturing. CMP effluents contain high
      concentrations of soluble copper and a complex mixture of organic constituents.
      The aim of this study is to perform a preliminary assessment of the treatability
      of CMP effluents in anaerobic sulfidogenic bioreactors inoculated with anaerobic
      granular sludge by testing individual compounds expected in the CMP effluents. Of
      all the compounds tested (copper (II), benzotriazoles, polyethylene glycol (M(n)
      300), polyethylene glycol (M(n) 860) monooleate, perfluoro-1-octane sulfonate,
      citric acid, oxalic acid and isopropanol) only copper was found to be inhibitory
      to methanogenic activity at the concentrations tested. Most of the organic
      compounds tested were biodegradable with the exception of perfluoro-1-octane
      sulfonate and benzotriazoles under sulfate reducing conditions and with the
      exception of the same compounds as well as Triton X-100 under methanogenic
      conditions. The susceptibility of key components in CMP effluents to anaerobic
      biodegradation combined with their low microbial inhibition suggest that CMP
      effluents should be amenable to biological treatment in sulfate reducing
      bioreactors.

PMID- 15857634
TI  - Removal of organic contaminants from soils by an electrokinetic process: the case
      of atrazine. Experimental and modeling.
AB  - The atrazine behaviour in soils when submitted to an electric field was studied
      and the applicability of the electrokinetic process in atrazine soil remediation
      was evaluated. Two polluted soils were used, respectively with and without
      atrazine residues, being the last one spiked. Four electrokinetic experiments
      were carried out at a laboratory scale. Determination of atrazine residues were
      performed by enzyme-linked immunosorbent assay (ELISA). The results show that the
      electrokinetic process is able to remove efficiently atrazine in soil solution,
      mainly towards the anode compartment: Estimations show that 30-50% of its initial
      amount is removed from the soil within the first 24h. A one-dimensional model is
      developed for simulating the electrokinetic treatment of a saturated soil
      containing atrazine. The movement of atrazine is modelized taking into account
      the diffusion transport resulting from atrazine concentration gradients and the
      reversed electro-osmotic flow at acidic soil pH.

PMID- 15857635
TI  - Arsenic leachability and speciation in cement immobilized water treatment sludge.
AB  - Arsenic leachability and speciation in cement immobilized water treatment sludge
      were investigated with leaching tests and X-ray absorption near edge structure
      (XANES) spectroscopy. The As leachability in the sludge determined with the
      toxicity characteristic leaching procedure (TCLP) and the waste extraction test
      (WET) was 283 and 7490 microgl(-1), respectively. Extractions with a lower liquid
      to solid ratio, under anaerobic conditions, and using citric acid buffer solution
      dramatically increased the leachate As concentration. XANES results showed that
      the As(III) composition was reduced from 51.1% of the total As content in the
      sludge to 16.3% in the cement treated sample with 28 days of cure. When the
      cement treated sample was cured for two years, the As(III) composition was
      decreased to 7.4%. The cement treatment reduced the As leachability. The leachate
      As(III) and total As concentrations were of the same order of magnitude in the
      samples cured for 28 days as for 2yr. However, consistently lower concentrations
      were detected in samples with longer cure time. The results of this study improve
      our understanding of arsenic speciation and leachability in the cement matrix
      after long cure times.

PMID- 15857636
TI  - Nitrilotriacetate- and citric acid-assisted phytoextraction of cadmium by Indian
      mustard (Brassica juncea (L.) Czernj, Brassicaceae).
AB  - In a pot experiment the effects of nitrilotriacetate (NTA) and citric acid
      applications on Cd extractibility from soil as well as on its uptake and
      accumulation by Indian mustard (Brassica juncea) were investigated. Plants were
      grown in a sandy soil with added CdS at four levels ranging from 50 to 200 mg Cd
      kg(-1) soil. After 30 days of growth, pots were amended with NTA or citric acid
      at 10 and 20 mmol kg(-1). Control pots were not treated with chelates. Harvest of
      plants was performed immediately before and one week after chelate addition. Soil
      water-, NH(4)NO(3)- and EDTA-extractable Cd fractions increased constantly with
      both increasing soil metal application and chelate concentration. Shoot dry
      weights did not suffer significant reductions with increasing Cd addition to the
      soil except for both NTA treatments in which at 200 mg Cd kg(-1) a 30% decrease
      in dry matter was observed. Generally, following NTA and citric acid amendments,
      Cd concentration in shoots increased with soil Cd level. However, due to Cd
      toxicity, at the highest metal application rate both NTA treatments lowered Cd
      concentration in the above-ground parts. Compared to the control, at 10 mmol kg(
      1) citric acid did not change Cd concentration in shoots, whereas NTA-treated
      plants showed an about 2-fold increase. The addition of chelates at 20 mmol kg(
      1) further enhanced Cd concentration in shoots up to 718 and 560 microg g(-1) dry
      weight in the NTA and citrate treatments, respectively.

PMID- 15857637
TI  - Effects of sewage sludge compost application on crops and cropland in a 3-year
      field study.
AB  - Composted sewage sludge can be applied to cropland to supply nutrients and
      improve soil physical properties. However, farmers are much concerned about heavy
      metal accumulation in cropland and heavy metal availability for crops. A 3-year
      field study was carried out in this study to investigate the effects of sewage
      sludge compost (SSC) application on the heavy metal accumulation in cropland
      soil, rapeseed germination and plumelet development, and yields of barley and
      Chinese cabbage, compared with conventional mineral fertilization. In addition,
      the availability of heavy metals for barley and Chinese cabbage was examined.
      Experimental results showed that SSC application produced little effects on
      rapeseed germination and stimulated the rape plumelet development at lower
      application rates (<150 ton ha(-1)). Heavy metals (Cu and Zn) were accumulated in
      the topsoil (0-20 cm), the barley grains and the cabbage leaves. The yields of
      barley and Chinese cabbage generated positive response to the SSC application.
      Addition of mineral N-P-K fertilizers into SSC could further increase the crop
      yield. Considering the heavy metals accumulation in cropland soil and their
      availability for crops, SSC should be applied to cropland at a limited
      application rate (<150 ton ha(-1)).

PMID- 15857638
TI  - Pathways and kinetics of carbon tetrachloride and chloroform reductions by nano
      scale Fe and Fe/Ni particles: comparison with commercial micro-scale Fe and Zn.
AB  - Groundwater and wastewater contaminated with chlorinated organic compounds (COCs)
      can be treated with zero-valent metals. The practicality of this treatment method
      depends on the reduction rates of the target compounds and their byproducts. In
      this study, nano-scale Fe and Fe/Ni particles were synthesized so that they could
      be used to rapidly degrade carbon tetrachloride (CT) and chloroform (CF). Their
      BET surface areas were around two orders higher than those of commercial micro
      scale Fe and Zn particles. Batch reduction experiments carried out with a metal
      loading of 2.5 gl(-1) showed that complete reduction of CT by the nano-scale
      Fe/Ni and Fe particles could be achieved within 20 min and 60 min, respectively.
      With the commercial micro-scale Fe and Zn particles applied at 125 gl(-1),
      complete CT reduction could only be achieved after 4h and 1.5h, respectively.
      Reductions of CT and CF with the nano-scale particles followed pseudo-first-order
      kinetics, and the specific reaction rate constants with the nano-scale Fe/Ni
      particles were 2-8 times higher than those of the nano-scale Fe particles. CT was
      degraded through hydrogenolysis to CF, and subsequently via both complete
      reduction pathway to methane and hydrogenolysis pathway to dichloromethane (DCM).
      Significantly more methane was generated with the use of the nano-scale Fe/Ni
      particles than with the nano-scale Fe particles. While the commercial Zn
      particles were more reactive than the commercial Fe particles, they failed to
      transform CT directly into methane, causing accumulation of DCM in the aqueous
      phase.

PMID- 15857639
TI  - The effects of preozonation on the biodegradability of mixed phenolic solution
      using a new gas-inducing reactor.
AB  - In this study, the effects of preozonation on the biodegradability of mixed 2
      chlorophenol/4-cresol solution were investigated using a new gas-inducing
      reactor, which can provide high ozone utilization efficiency. The decomposition
      rate of phenolic mixture, COD removal and TOC removal increases with increasing
      pH. A half-order overall kinetic model can correctly describe the decomposition
      of phenolic mixture. The BOD(5)/COD ratio of the preozonized solutions increases
      with increasing preozonation time, indicating that preozonation can enhance the
      biodegradability. Based on high ozone utilization rate, it is concluded that the
      best characteristic time can be chosen at the rapid increase of ozone gas outlet
      concentration. Since the ozone gas outlet concentration can be easily monitored,
      it is a useful real-time control parameter in preozonation.

PMID- 15857640
TI  - Mobilization of phenol and dichlorophenol in unsaturated soils by non-uniform
      electrokinetics.
AB  - The poor mobility of organic pollutants in contaminated sites frequently results
      in slow remediation processes. Organics, especially hydrophobic compounds, are
      generally retained strongly in soil matrix as a result of sorption,
      sequestration, or even formation into non-aqueous-phase liquids and their
      mobility is thus greatly reduced. The objective of this study was to evaluate the
      feasibility of using non-uniform electrokinetic transport processes to enhance
      the mobility of organic pollutants in unsaturated soils with no injection
      reagents. Phenol and 2,4-dichlorophenol (2,4-DCP), and kaolin and a natural sandy
      loam soil were selected as model organics and soils, respectively. The results
      showed that non-uniform electrokinetics can accelerate the desorption and
      movement of phenol and 2,4-DCP in unsaturated soils. Electromigration and
      electroosmotic flow were the main driving forces, and their role in the
      mobilization of phenol and 2,4-DCP varied with soil pH. The movement of 2,4-DCP
      in the sandy loam towards the anode (about 1.0 cmd(-1)V(-1)) was 1.0-1.5 cmd(
      1)V(-1) slower than that in the kaolin soil, but about 0.5 cmd(-1)V(-1) greater
      than that of phenol in the sandy loam. When the sandy loam was adjusted to pH
      9.3, the movement of phenol and 2,4-DCP towards the anode was about twice and
      five times faster than that at pH 7.7, respectively. The results also
      demonstrated that the movement of phenol and 2,4-DCP in soils can be easily
      controlled by regulating the operational mode of electric field. It is believed
      that non-uniform electrokinetics has the potential for practical application to
      in situ remediation of organics-contaminated sites.

PMID- 15857641
TI  - Degradation of aqueous carbon tetrachloride by nanoscale zerovalent copper on a
      cation resin.
AB  - Nanoscale zerovalent copper supported on a cation resin was successfully
      synthesized to enhance the removal of carbon tetrachloride (CCl(4)) from
      contaminated water. The use of the cation resin as a support prevents the
      reduction of surface area due to agglomeration of nanoscale zerovalent copper
      particles. Moreover, the cation resin recycles the copper ions resulting from the
      reaction between CCl(4) and Cu(0) by simultaneous ion exchange. The decline in
      the amount of CCl(4) in aqueous solution results from the combined effects of
      degradation by nanoscale zerovalent copper and sorption by the cation resin; thus
      the amount of CCl(4) both in aqueous solution and sorbed onto the resin were
      measured. The pseudo-first-order rate constant normalized by the surface-area and
      the mass concentration of nanoscale zerovalent copper (k(SA)) was 2.1+/-0.1 x 10(
      2)lh(-1)m(-2), approximately twenty times that of commercial powdered zerovalent
      copper (0.04 mm). Due to the exchange between Cu(2+) and the strongly acidic ions
      (H(+) or Na(+)), the pH was between 3 and 4 in unbuffered solution and Cu(2+) at
      the concentration of less than 0.1 mg l(-1) was measured after the dechlorination
      reaction. In the above-ground application, resin as a support would facilitate
      the development of a process that could be designed for convenient emplacement
      and regeneration of porous reductive medium.

PMID- 15857642
TI  - Copper-binding efficacy of water-soluble chitosans: characterization by aqueous
      binding isotherms.
AB  - The major objective of the study is to measure directly the isotherms of copper
      binding onto soluble chitosan preparations, using ion-selective electrode
      technique. Copper uptake is found to decrease strongly when chitosan acetylation
      degree or chitosan concentration increased. When relating the bound copper
      concentrations to content of non-acetylated amine groups in a chitosan,
      differences between copper uptake on different chitosan preparations become
      reduced but not disappear. Other effects, in addition to the contents of non
      acetylated amine groups, can involve differences in the copper binding by
      different chitosans. Due to isotherm non-linearity, the distribution coefficient
      K(d) of copper between a water-soluble chitosan and an aqueous solution may vary
      by two orders of magnitude as the free copper concentration C(free) varied.
      Linear relation between logK(d) normalized by free amine group content of
      chitosans and logC(free) may help in preliminary estimating of the copper binding
      by water-soluble chitosans at a certain pH.

PMID- 15857643
TI  - Effect of various reaction parameters on THMs aqueous sonolysis.
AB  - Ultrasonic irradiation was investigated for destruction of the following THMs:
      CHCl(3), CHBrCl(2), CHBr(2)Cl, CHBr(3), and CHI(3). The effect of pH,
      temperature, and the organics initial concentration on the THMs sonodegradation
      at acoustic frequency of 20 kHz was studied. An increase of the solution
      temperature resulted in a faster sonodegradation rates. Initial aqueous solution
      pH, in the range from 3 to 10, was found to have little effect on the degradation
      of the THMs. The THMs sonolysis efficiency was reduced when the initial organic
      compounds concentration was increased from 10 mg l(-1) to 300 mg l(-1).

PMID- 15857644
TI  - Bioaugmentation with a Bacillus sp. to reduce the phytoavailable Cd of an
      agricultural soil: comparison of free and immobilized microbial inocula.
AB  - In order to reduce the cadmium potentially available for plants, soil
      bioaugmentation was performed by using a Bacillus sp. In a pot experimentation,
      sterilized and non-sterilized soils were inoculated using free or immobilized
      cells entrapped in alginate beads. This test was carried out with different
      inoculum sizes (2 x 10(10) and 2 x 10(11)CFU kg(-1) dw of soil) and alginate bead
      compositions (10 and 15 g of both alginate and CaCl(2) l(-1)). Then, the soil
      pots were incubated at 20 degrees C and the soil humidity was kept at a level of
      20%. After 3 weeks of a batch incubation, the potentially phytoavailable Cd was
      reduced up to a factor of 14. The bioaugmentation resulted in the soil
      colonization by Bacillus sp. thanks to an increase of the cell concentration up
      to 1.8 log units. However, in comparison to the cells being inoculated in a free
      mode, the immobilization of the cells did not significantly improve the survival
      of the cells in the soil. Although the resulting effect not being highly
      pronounced, the potentially phytoavailable Cd correlated with the cell
      concentration in a surprisingly positive way. What is more, the Bacillus
      concentrations in the soil were positively correlated with the inoculum, too.

PMID- 15857645
TI  - Polychlorinated dibenzo-dioxins and -furans detoxification of soil promoted by K
      polyethylene glycol technology.
AB  - The detoxification of soil and sludge from polychlorinated dibenzo-dioxins (PCDD)
      and -furans (PCDF) has been achieved by means of the K-PEG technology based on
      the in situ formation of the complex between polyethylene glycol (PEG) and KOH.
      Dechlorination of the pollutants was promoted by heating the samples up to 250
      degrees C, above the PEG thermal degradation onset (>140 degrees C). As a
      consequence, a bursting evolution of hydrogen was observed which gave a reductive
      character to the reaction media and atmosphere. PCDD and PCDF chlorine atoms were
      progressively eliminated by a hydrodehalogenation reaction. After optimisation of
      the experimental parameters, the toxicity index was lowered more than 98%. In
      order to gain insight on the mechanism of the reaction, PEG thermal degradation
      chemistry was studied in some detail. The analytical results (mainly by mass and
      IR spectroscopy) suggest that PEG has an essential role on promoting the
      dehalogenation reaction by acting as a phase transfer agent as well as a source
      of hydride.

PMID- 15857646
TI  - Identification of chemical substances in industrial wastes and their pyrolytic
      decomposition products.
AB  - In order to quantify the sources of chemical pollutants in the leachate from
      reclaimed wastes, chemical substances in 11 different types of industrial wastes
      were identified. Their elution behaviors were also investigated. Alkanes (5.3-890
      ng g(-1)), benzenes (8.1-110 ng g(-1)), polyaromatic hydrocarbons (PAHs) (3.2-560
      ng g(-1)), alcohols, steroids, phenol (7.1 ng g(-1)), ketones, furans (190-210 ng
      g(-1)), phthalates (8.9-560 ng g(-1)), benzoquinones, dibenzothiophene (190 ng g(
      1)), benthiocarb (4.2 ng g(-1)), sulfur, nitrile compounds, amino compounds,
      amido compounds, pyridines, quinolines (1.8-15 ng g(-1)), isoquinolines,
      carbazoles, acridines, chlordenes (1.5-1.6 ng g(-1)) and nonachlors (1.1-1.6 ng
      g(-1)) were detected in 9 types of industrial wastes. The chemical substances
      detected in waste at the highest concentrations were alkanes, PAHs and
      phthalates. Water supply sludge, dust and brick garbage contained many kinds of
      chemical substances. The elution behaviors of specific chemical substances, COD
      and nutrients varied by characteristic and production process of each waste. Over
      100 different compounds were detected in pyrolysis products including
      carbohydrate, carotynoid, amino acids, proteins, humic acids, lignin and
      combustion products.

PMID- 15857647
TI  - Effect of formaldehyde on Cu(II) removal from synthetic complexed solutions by
      ion exchange.
AB  - The effect of formaldehyde (HCHO) on the ion exchange of Cu(II) from an equimolar
      EDTA (ethylenediaminetetraacetic acid, H(4)L) solution with a strong-base
      Amberlite IRA-400 resin was studied. Experiments were conducted as a function of
      the initial concentration of Cu(II) (0.5-10 mM), solution pH (1.0-6.0), HCHO
      concentration (0-6 vol%), and temperature (15-35 degrees C). It was shown that
      the amount of exchange of Cu(II), which exists in the form of complexed anions
      CuL(2-), increased with increasing solution pH and reached a plateau at an
      equilibrium pH (pH(e)) of 3.5. However, the amount of exchange decreased with
      increasing HCHO concentration up to 3 vol% but then slightly decreased with a
      further increase in HCHO concentration. Such effect of added HCHO was determined
      by the following two factors: the competitive exchange of HCOO(-) anions and the
      enhanced exchange of Cu(I) in the form of complexed anions CuL(3-). The exchange
      isotherm obtained at a fixed pH(e) could be well described by the Langmuir
      equation. The isosteric enthalpy change for the present ion exchange process was
      also evaluated and discussed.

PMID- 15857648
TI  - Growth of Azotobacter chroococcum in chemically defined media containing p
      hydroxybenzoic acid and protocatechuic acid.
AB  - Growth and utilization of different phenolic acids present in olive mill
      wastewater (OMW) by Azotobacter chroococcum were studied in chemically defined
      media. Growth and utilization of phenolic acids were only detected when the
      microorganism was cultured on p-hydroxybenzoic acid at concentration from 0.01%
      to 0.5% (w/v) and protocatechuic acid at concentration from 0.01% to 0.3% (w/v)
      as sole carbon sources suggesting that only these phenolic compounds could be
      utilized as a carbon source by A. chroococcum. Moreover when culture media were
      added with a mixture of 0.3% of protocatechuic acid and 0.3% p-hydroxybenzoic
      acid, the microorganism degradated in first place protocatechuic acid and once
      the culture medium was depleted of this compound, the degradation of p
      hydroxybenzoic acid commenced very fast.

PMID- 15857649
TI  - The preparation of Zn2+-doped TiO(2) nanoparticles by sol-gel and solid phase
      reaction methods respectively and their photocatalytic activities.
AB  - The photocatalytic oxidation of the organic pollutants with TiO(2) as
      photocatalyst has been widely studied in the world, and many achievements have
      been made. The degradation of pollutants is highly related to the photocatalytic
      activity of TiO(2). It is demonstrated that doping ions to TiO(2) is one way to
      enhance the photocatalytic activity of TiO(2). In this paper, Zn(2+)-doped TiO(2)
      nanoparticles were prepared through sol-gel and solid phase reaction methods,
      characterized by means of X-ray diffraction (XRD) and transmission electron
      microscopy (TEM). The photocatalytic activity of the elaborated powders was
      studied following the degradation of Rhodamine B. The results showed that the
      photocatalytic activity of Zn(2+)-doped TiO(2) prepared by sol-gel method is
      close to that of pure TiO(2) particles, however, the photocatalytic activity of
      Zn(2+)-doped TiO(2) prepared by solid phase reaction method is much higher than
      that of pure TiO(2) particles. The most efficient degradation of Rhodamine B was
      found with TiO(2) particles doped with 0.5% Zn(2+) in mole and calcined at 500
      degrees C. Also the reason for the enhancement of the photocatalytic activity of
      TiO(2) by Zn(2+) doping through solid phase reaction method was discussed.

PMID- 15857650
TI  - Late Pliocene hominid knapping skills: the case of Lokalalei 2C, West Turkana,
      Kenya.
AB  - Relatively few remains of Late Pliocene hominids' knapping activities have been
      recovered to date, and these have seldom been studied in terms of manual
      dexterity and technical achievements. With regard to early hominid technological
      development, the evidence provided by the data from 2.34 Myr site of Lokalalei 2C
      (Kenya) questions both the prior assumption of a continuous and linear
      evolutionary trend in lithic production and the idea that it long remained
      static. The level of elaboration evinced by the lithic assemblage is quite
      unexpected in view of its age, and seemingly more advanced that what can be
      surmised for other Late Pliocene East-African sites, including the nearby site of
      Lokalalei 1. Analysis relies mainly on the dynamic reconstruction of entire
      cobble reduction sequences from particularly informative refitting groups. The
      Lokalalei 2C knappers had already internalised the notion of planning and
      foresight in raw material procurement and management. Beyond simple mastery of
      the basic technical constraints peculiar to stone knapping, they conducted a
      highly controlled debitage of flakes following constant technical rules and
      resulting in high productivity. The data suggest that early hominids displayed
      distinct technical competencies and techno-economic patterns of behavior, thus
      pointing to an intrasite complexity and intersite diversity which are not
      accounted for by the existing chrono-cultural classifications.

PMID- 15857651
TI  - Craniodental biomechanics and dietary toughness in the genus Cebus.
AB  - The tufted capuchin (Cebus apella) has been used in a number of comparative
      studies to represent a primate with craniofacial morphology indicative of hard
      object feeding. Researchers have specifically referred to the tufted capuchin as
      a seed predator. Craniofacial features exhibited by the tufted capuchin, such as
      thick cortical bone in the mandibular corpus and symphysis, and a broad face
      associated with large masticatory muscles, permit the production and dissipation
      of relatively high masticatory forces. These morphologies, however, cannot
      distinguish between the tufted capuchin's propensity to exert higher forces when
      opening food with its anterior dentition or with its cheek teeth. It is also
      unclear whether these are adaptations for biting or chewing foods. This study
      uses a constrained lever model to compare the masticatory adaptations of C.
      apella to other cebids and atelids. Results show that the temporalis and masseter
      muscles in C. apella and C. olivaceus are more anteriorly positioned relative to
      nine other platyrrhine taxa. This condition, which appears to be ancestral among
      the Cebinae, increases force production at the incisors and canines while
      compromising third molar function. Cebus apella, has exaggerated this pattern.
      Field data on dietary toughness show that both capuchins typically select foods
      of low toughness, but on occasion, C. apella ingests food items of exceptional
      toughness. Thus, C. apella appears to maintain these biomechanical relationships
      by producing particularly high but relatively infrequent bite forces,
      particularly at the incisors and canines. However, adaptations for anterior
      dental use do not tightly constrain the diet of Cebus apella. This approach can
      be used to clarify the dietary adaptations of fossil taxa.

PMID- 15857652
TI  - A Mid-Upper Palaeolithic human humerus from Eel Point, South Wales, UK.
AB  - We report here on a human humerus directly dated to 24,470 +/- 110 BP, placing it
      within the Gravettian, or Mid-Upper Palaeolithic. The partial humerus is an
      isolated find and can be attributed (with some caution) to the Pleistocene 'bone
      cave' of Eel Point on Caldey Island, Wales (UK). The humerus is probably male,
      similar in robusticity to other Gravettian right humeri. The apparent absence of
      stone tools and presence of hyaena bone and coprolites suggest that the element
      may not derive from an intentional burial. After a maxilla from Kent's Cavern and
      the Gravettian Paviland 1, Eel Point represents the third oldest anatomically
      modern human known from Britain. Stable carbon and nitrogen isotope measurements
      do not support certain use of marine foods but highlight the need for more
      research on contemporary faunal remains in order to better interpret human values
      from this period.

PMID- 15857653
TI  - Revised correlation of the Haritalyangar magnetostratigraphy, Indian Siwaliks:
      implications for the age of the Miocene hominids Indopithecus and Sivapithecus,
      with a note on a new hominid tooth.

PMID- 15857654
TI  - Early Pleistocene "hominid remains" from southern Spain and the taxonomic
      assignment of the Cueva Victoria phalanx.

PMID- 15857655
TI  - Flake recovery rates and inferences of Oldowan hominin behavior: a response to
      Kimura 1999, 2002.

PMID- 15857656
TI  - Production and purification of ovine anti-tetanus antibody.
AB  - We used the ovine as bioreactor for the production and optimization of anti
      tetanus toxin antibody. Four female sheep were immunized with human tetanus
      vaccine (TT-alum) every two weeks for 16 weeks, after which serum was collected
      and its titer was estimated by ELISA. The highest titer obtained was 39,000 IU ml
      1. To optimize a purification protocol for ovine anti-tetanus toxin, we used four
      procedures; weak anion (DEAE-Sephadex), weak cation (CM-Sephadex), ammonium
      sulfate precipitation alone or in combination with caprylic acid. Fifty percent
      saturation with ammonium sulfate combined with caprylic acid gave us the highest
      yield of protein with specific activity and the purest Fab product.

PMID- 15857657
TI  - Influence of bacteriocin-like substance, generation times, and genetic profiles
      of Listeria innocua on the isolation of Listeria monocytogenes.
AB  - Inhibition of isolation of Listeria monocytogenes by bacteriocin-like substance
      (BLS)-producing Listeria innocua after enrichment culture was investigated. When
      26 L. monocytogenes strains were examined in combination with eight L. innocua
      strains using the spot on lawn method, 52/208 (25.0%) combinations showed the
      growth inhibition of L. monocytogenes. When two Listeria species were cultured
      simultaneously in selective enrichment broth, inhibition of isolation of L.
      monocytogenes was observed in 12/52 of the combinations at 24h (23.1%), in 24/52
      at 48h (46.2%) and in 30/52 (57.7%) after 7 days of incubation. The randomly
      amplified polymorphic DNA profiles showed no interstrain similarities between
      either strains of the BLS-producing L. innocua or the BLS-sensitive L.
      monocytogenes strains. Therefore inhibition by BLS-producing L. innocua of
      isolation of L. monocytogenes after enrichment culture is unlikely to be
      dependent upon a particular genetic profile.

PMID- 15857658
TI  - Experimental infection of calves with a gI, gE, US9 negative bovine herpesvirus
      type 5.
AB  - In this work, a role for the genes encoding glycoproteins I (gI) and E (gE) and
      the US9 protein of bovine herpesvirus type 5 (BHV-5) in neuropathogenicity and
      reactivation of latent infections was examined. Calves infected intranasally with
      a gI/gE/US9 deleted recombinant shed up to 10(2.85) TCID50/ml infectious virus in
      nasal secretions. Calves infected with the wild type BHV-5 parental virus shed up
      to 10(5) TCID50/ml virus. No signs of disease were observed in calves infected
      with the recombinant virus, whereas those infected with wild type virus displayed
      respiratory and neurological signs. The recombinant was only able to reach the
      basal portions of the central nervous system. In contrast, wild type virus was
      found widespread within the brain. Reactivation with dexamethasone 60 days post
      infection resulted in reactivation of wild type virus, whereas the recombinant
      virus could not be reactivated. These studies demonstrate that genes gI, gE and
      US9 of BHV-5 are important for its neuropathogenicity and its ability to reactive
      from latency.

PMID- 15857659
TI  - GIS-facilitated spatial epidemiology of tick-borne diseases in coyotes (Canis
      latrans) in northern and coastal California.
AB  - Ixodes pacificus is the main tick vector for transmission of Anaplasma
      phagocytophilum and Borrelia burgdorferi to large vertebrates in California. The
      present study was undertaken in I. pacificus-infested counties in California to
      examine spatial and temporal relationships among A. phagocytophilum and B.
      burgdorferi-exposed coyotes with vegetation type and climate. The overall A.
      phagocytophilum and B. burgdorferi seroprevalences were 39.5% (N=215) and 18.9%
      (N=148), respectively, with no association with sex. PCR for A. phagocytophilum
      and B. burgdorferi was negative in all blood and kidney samples. Increased
      seroprevalence was a positive function of rainfall. Ehrlichial seropositivity was
      increased in blue-oak foothill pine, montane hardwood, and redwood vegetation
      regions, and decreased in coastal sagebrush and cropland. Increased exposure to
      B. burgdorferi occurred in blue oak woodland.

PMID- 15857660
TI  - T cell function in tuatara (Sphenodon punctatus).
AB  - Tuatara are the sole survivors of an entire order of reptiles that thrived during
      the age of the dinosaurs. Therefore, knowledge of their physiology is critical to
      understanding the phylogeny of reptiles. Previous studies of the immune system of
      the tuatara did not assess T cell function. We analyzed T cell function among six
      captive tuatara by assessing concanavalin A (Con A), phytohemagglutinin (PHA) and
      mixed lymphocyte reaction (MLR) induced T cell proliferation. Peripheral blood
      mononuclear cells from six out of six and four out of four tuatara tested
      exhibited significant proliferative responses to Con A and PHA, respectively, as
      measured by an MTT reduction assay. A lower level of proliferation was detected
      in an MLR. However, Con A activated lymphocytes were not cytotoxic for a
      xenogeneic murine mastocytoma cell line (P815).

PMID- 15857661
TI  - Mycobacterium avium subsp. paratuberculosis enters the small intestinal mucosa of
      goat kids in areas with and without Peyer's patches as demonstrated with the
      everted sleeve method.
AB  - The main lesions of paratuberculosis in ruminants are in the small intestine.
      Previous studies have shown that the bacterium enters the small intestine through
      M cells found in the follicle-associated epithelium lining the domes of the
      Peyer's patches. The everted sleeve method, devised for the in vitro study of
      intestinal absorption, was used in this study to investigate the uptake of
      Mycobacterium avium subsp. paratuberculosis in goat intestine. Everted small
      intestinal sleeves of goat kids, prepared from areas with and without Peyer's
      patches, were incubated for 60 min in 3H-labeled bacterial solution. The results
      of this study imply that the bacteria can enter the intestinal mucosa of the
      jejunum, both in areas with and without Peyer's patches. These findings indicate,
      therefore, that M. avium subsp. paratuberculosis bacteria not only enter through
      M cells but also through enterocytes.

PMID- 15857662
TI  - Role of host's antitumor immunity in exercise-dependent regression of murine T
      cell lymphoma.
AB  - We have reported that the ascitic growth of a transplantable T cell lymphoma of
      spontaneous origin, designated as Dalton's lymphoma (DL), is associated with a
      concomitant immunosuppression. We have also reported that progressive in vivo
      growth of DL resulted in an inhibition of macrophage functions. In present
      investigation we report that physical exercise by DL-bearing mice, on a treadmill
      on a daily basis for various time durations for 10 days, increased the life span
      along with an inhibition of tumor growth. A significant decrease in the volume of
      ascitic fluid and number of cells in the tumor was obtained in mice, which
      underwent exercise. DL cells obtained from exercised groups showed a decreased
      proliferation in vitro. An augmentation in the percent of cells showing apoptotic
      morphology and percent specific DNA fragmentation was observed, suggesting that
      physical exercise increased the incidence of apoptosis in tumor cells. Moreover,
      macrophages obtained from tumor-bearing mice, which underwent exercise training,
      showed an augmented tumoricidal activity and production of tumoricidal molecules
      like interleukin-1 (IL-1), tumor necrosis factor (TNF) and nitric oxide (NO). On
      the basis of this study it is suggested that the regression of tumor growth
      consequent to physical exercise training of tumor bearing host, may be due to an
      exercise-dependent augmentation of macrophage tumoricidal functions.

PMID- 15857663
TI  - Protein kinase A mediates regulation of gap junctions containing connexin35
      through a complex pathway.
AB  - Connexin 35 (Cx35) is a major component of electrical synapses in the central
      nervous system. Many gap junctions containing Cx35 are regulated by dopamine
      receptor pathways that involve protein kinase A (PKA). To study the mechanism of
      PKA regulation, we analyzed direct phosphorylation of Cx35 by PKA in vitro and
      studied the regulation of neurobiotin tracer coupling in HeLa cells expressing
      Cx35 or Cx35 mutants that lack phosphorylation sites. In Cx35-transfected cells,
      application of the PKA activator Sp-8-cpt-cAMPS caused a significant decline in
      coupling, while a PKA inhibitor, Rp-8-cpt-cAMPS, significantly increased tracer
      coupling. In vitro phosphorylation and mutagenic analysis showed that PKA
      phosphorylates Cx35 directly at two major sites, Ser110 in the intracellular loop
      and Ser276 in the carboxyl terminus. In addition, a minor phosphorylation site in
      the C-terminus was identified by truncation of the last 7 amino acids at Ser298.
      The mutations Ser110Ala or Ser276Ala significantly reduced regulation of coupling
      by the PKA activator while a combination of the two eliminated regulation.
      Truncation at Ser298 reversed the regulation such that the PKA activator
      significantly increased and the PKA inhibitor significantly decreased coupling.
      The activation was eliminated in the S110A, S276A, S298ter triple mutant. We
      conclude that PKA regulates Cx35 coupling in a complex manner that requires both
      major phosphorylation sites. Furthermore, the tip of the C-terminus acts as a
      "switch" that determines whether phosphorylation will inhibit or enhance
      coupling. Reliance on the combined states of three sites provides fine control
      over the degree of coupling through Cx35 gap junctions.

PMID- 15857664
TI  - Mouse motor neuron disease caused by truncated SOD1 with or without C-terminal
      modification.
AB  - Mutation of Cu/Zn superoxide dismutase (SOD1) contributes to a portion of the
      cases of familial amyotrophic lateral sclerosis (FALS). We previously reported on
      a FALS family whose members had a mutant form of SOD1 characterized by a 2-base
      pair (bp) deletion at codon 126 of the SOD1 gene. To investigate the cellular
      consequences of this mutation, we produced transgenic mice that expressed normal
      and mutated copies of human SOD1: wild-type SOD1 (W), wild-type SOD1 with a FLAG
      epitope at C-terminal (WF), mutated SOD1 with the 2-bp deletion (D), and SOD1
      with the 2-bp deletion with FLAG (DF). The mice heterozygotic for the human
      mutated SOD1 (D and DF) showed distinct ALS-like motor symptoms, whereas the mice
      heterozygotic for the normal SOD1 (W and WF) mice did not. Homozygotes of D and
      DF lines showed the ALS symptoms at an earlier age and died earlier than the
      heterozygotes. By Northern blot analysis, the mRNAs for all human SOD1s were
      confirmed in these lines. All the human SOD1 proteins, except the D mutant, were
      detectable by immunoblot. The D protein was only confirmed when it was
      concentrated by immunoprecipitation. Neuropathologically, loss of spinal motor
      neurons and reactive gliosis were common features in the symptomatic lines. The
      remaining motor neurons in these mice also exhibited eosinophilic inclusions. The
      biochemical and pathological characteristics of these mice are quite similar to
      those of human FALS patients with same mutation. This intriguing model will
      provide an important source of information of the pathogenesis of FALS.

PMID- 15857665
TI  - Delayed hypothermia preferentially increases expression of brain-derived
      neurotrophic factor exon III in rat hippocampus after asphyxial cardiac arrest.
AB  - Brain-derived neurotrophic factor (BDNF) protein levels increase in rats treated
      with a regimen of delayed, mild hypothermia that improve neurological recovery
      after asphyxial cardiac arrest. BDNF transcription in rat brain involves at least
      five different BDNF exons (exons I-V) that produce four different varieties of
      mRNA, each containing exon V paired with one of exons I-IV. This study examined
      whether these different BDNF transcripts are differentially affected by cardiac
      arrest and by therapeutic hypothermia in rat hippocampus using a reverse
      transcription and PCR-based method. At 24 h after asphyxial cardiac arrest,
      transcripts containing exons I and III increased. In rats treated with
      hypothermia after cardiac arrest, transcripts containing exon III were further
      increased. No significant alterations in transcripts from exons II or IV were
      observed, though there was a trend for hypothermia to decrease message from these
      exons. These data suggest that hypothermia after cardiac arrest produces exon
      specific changes in BDNF transcription.

PMID- 15857666
TI  - Rhythmic expression of clock-controlled genes in retinal photoreceptors is
      sensitive to 18-beta-glycyrrhetnic acid and 18-alpha-glycyrrhetnic acid-3
      hemisuccinate.
AB  - Chicken retina contains circadian oscillators that drive rhythmic transcription
      of several genes expressed in photoreceptor cells. To determine if gap junctions
      assist in coordinating these transcript rhythms, we examined the effects of two
      compounds, 18alpha-glycyrrhetnic acid-3-hemisuccinate (ACO) and 18beta
      glycyrrhetnic acid (18beta-GA), on photoreceptor iodopsin and arylalkylamine N
      acetyltransferase (AANAT) transcript rhythms in embryonic chicken retinal explant
      cultures that were maintained under different lighting conditions. Both
      compounds, whose actions include reversibly block gap junction permeability,
      produced rapid and sustained reductions in iodopsin and AANAT mRNA levels, but
      did not alter the levels of guanylate cyclase activating protein-1 (GCAP1) mRNA,
      a noncircadian-regulated, photoreceptor-specific gene. The iodopsin and AANAT
      mRNA rhythms re-emerged in the cultured retinas within 24 h of removal of the
      compounds. These results show that the effects of ACO and 18beta-GA on iodopsin
      and AANAT mRNA levels were not due to generalized suppression of gene
      transcription. The dramatic reduction in the levels of iodopsin and AANAT mRNA
      induced by these compounds suggests a mechanism of action that directly affects
      the synthesis and/or degradation of these transcripts rather than the
      synchronization or function of the retinal oscillators that drive transcription
      of these genes.

PMID- 15857667
TI  - Zinc-induced anti-apoptotic effects in SH-SY5Y neuroblastoma cells via the
      extracellular signal-regulated kinase 1/2.
AB  - Zinc levels are increased in brain areas severely affected by Alzheimer's disease
      (AD) pathologies. Zinc has both protective and neurotoxic properties and can
      stimulate both phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein
      kinase (MAPK) pathways. Several kinases related to these pathways including
      protein kinase B (PKB), p70 S6 kinase (p70S6K), and extracellular signal
      regulated kinase 1/2 (ERK1/2) are known cell survival factors and are
      overactivated in neurons bearing neurofibrillary tangles (NFTs) in AD. The
      present study aimed to determine whether anti-apoptotic effects of zinc are
      mediated via these signaling pathways. Zinc was used to treat SH-SY5Y
      neuroblastoma cells and effects investigated in relation to PKB, p70S6K, and
      ERK1/2 in the absence and presence of the pro-apoptotic agent staurosporine
      (STS). Cell damage was evaluated by measuring levels of DNA fragmentation as well
      as the WST-1 assay for cell viability. Results indicated that: (1) treatment with
      high doses of zinc (>/=400 microM) for short time periods (</=2 h) gave rise to
      increased levels of DNA fragments, increased cell membrane permeability, and
      reduced mitochondria membrane potential; (2) treatment with 100 microM zinc for
      >2 h reversed an increased DNA fragmentation due to U0126 inhibition of ERK1/2;
      (3) increased DNA fragmentation due to STS could be protected against by 100
      microM zinc; (4) the protective effects of 100 microM zinc on STS-induced DNA
      fragmentation could be partially reversed by U0126. These results indicate that a
      zinc-induced anti-apoptotic response in SH-SY5Y cells likely occurs through
      ERK1/2.

PMID- 15857668
TI  - Down-modulation of the CXCR4 co-receptor by intracellular expression of a single
      chain variable fragment (SFv) inhibits HIV-1 entry into primary human brain
      microvascular endothelial cells and post-mitotic neurons.
AB  - Our laboratories previously demonstrated that expression of a single chain
      variable antibody fragment (SFv), anti-CXCR4 SFv, in human lymphoid cells
      suppresses surface display of the chemokine co-receptor CXCR4 and inhibits
      infectious entry of human immunodeficiency virus type I (HIV-1). We now sought to
      extend these results to two types of central nervous system (CNS) cells, primary
      isolated human brain microvascular endothelial cells (MVECs), and post-mitotic
      differentiated human neurons, both of which normally express significant levels
      of CXCR4. The anti-CXCR4 SFv expression construct was delivered using an HIV-1
      based vector, and control cells received LacZ-expressing viral particles. Upon
      intracellular expression of the anti-CXCR4 SFv, immunostaining revealed a marked
      reduction in surface display of CXCR4 on both cell types. Consequently, post
      mitotic neurons expressing the anti-CXCR4 SFv were significantly protected from
      HIV-1 infection, as measured by HIV-1 p24 antigen production, and partial
      protection was observed in human brain MVECs. The ability to selectively down
      modulate the surface expression of CXCR4 in CNS cells may allow for the
      development of clinical molecular therapy strategies against HIV-1-related
      neurodegenerative disorders and neuroinvasion.

PMID- 15857669
TI  - Retinal G-substrate, potential downstream component of NO/cGMP/PKG pathway, is
      located in subtype of retinal ganglion cells and amacrine cells with protein
      phosphatases.
AB  - The aim of this study was to determine the distribution and function of G
      substrate, a specific substrate of the nitric oxide (NO)-cyclic guanosine
      monophosphate (cGMP)-cGMP-dependent protein kinase (PKG) signaling pathway, in
      normal rat retina and in G-substrate knockout mice. The retinas of adult wild
      type rats and mice and G-substrate knockout mice were studied
      immunohistologically to characterize the upstream and downstream components of
      the NO-cGMP-PKG pathway. Immunoblot analysis showed that the molecular weight of
      retinal G-substrate was similar to that of cerebellar G-substrate. In adult rats
      and mice, retinal G-substrate was located in a subpopulation of amacrine cells
      and in C38-positive retinal ganglion cells (RGCs) but not in alpha RGCs. In
      addition, retinal G-substrate was co-expressed with other upstream and downstream
      signaling components of the NO-cGMP-PKG-G-substrate-phosphatase pathway in the
      adult retina. Electroretinographic (ERG) analysis demonstrated that there was no
      significant difference between the ERGs of wild-type and G-substrate knockout
      mice. These results suggest that retinal G-substrate plays a role as a downstream
      component of the NO-cGMP-PKG pathway. The co-localization of retinal G-substrate
      with protein Ser/Thr phosphatases suggests that it acts as an endogenous protein
      phosphatase inhibitor as in the cerebellum.

PMID- 15857670
TI  - Glucose injection reduces neuropeptide Y and agouti-related protein expression in
      the arcuate nucleus: a possible physiological role in eating behavior.
AB  - Evidence suggests that neuropeptide Y (NPY) and agouti-related protein (AgRP) in
      the arcuate nucleus (ARC) are modulated by glucoregulatory hormones and involved
      in maintaining normal eating patterns and glucose homeostasis in states of energy
      deficiency. This study investigated whether these peptides respond to glucose
      itself under conditions, e.g., before the nocturnal feeding cycle, when
      carbohydrate stores are low. After removal of food 3 h before dark onset, Sprague
      Dawley rats were given a single, intraperitoneal (i.p.) injection of saline or
      10% glucose (0.13 g/kg) and were sacrificed at different intervals, from 3.5 to
      90 min later, for measurements of circulating hormones and metabolites or of NPY
      and AgRP mRNA in the ARC. With no change in insulin, leptin, or triglycerides,
      glucose injection produced a 1.8-mM rise in circulating glucose during the first
      15 min, followed by a 30-60% reduction in NPY and AgRP mRNA at 30 and 60 min post
      injection. A similar effect was observed with intraventricular administration of
      5% glucose. At 90 min, however, this suppressive effect of i.p. glucose relative
      to saline was lost and actually reversed into a 50% increase in NPY and AgRP,
      possibly attributed to a decline in circulating glucose followed by a 50% rise in
      corticosterone at 60 min. These biphasic shifts over a 90-min period may reflect
      mechanisms underlying natural eating patterns at the onset of the nocturnal
      cycle, when spontaneous meals are approximately 90 min apart and rich in
      carbohydrate, glucose levels are low, and corticosterone and ARC peptides
      naturally peak.

PMID- 15857671
TI  - Presence of splice variant forms of cytochrome P4502D1 in rat brain but not in
      liver.
AB  - Cytochromes P450 (P450), a family of heme-containing proteins, is involved in the
      oxidative metabolism of both foreign and endogenous compounds. Although liver is
      quantitatively the major organ involved in the metabolism of most xenobiotics,
      there is increasing evidence that these enzymes are present in extrahepatic
      tissues, such as lung, kidney, brain, etc and they may contribute to the in situ
      metabolism of xenobiotics in these organs. The possible relationship between
      genetic polymorphism seen in P4502D6 and incidence of neurodegenerative diseases,
      such as Parkinson's disease, has prompted the characterization of P4502D enzymes
      in rat brain. In the present study, we demonstrate that P4502D1 (the rat
      homologue of human P4502D6) is constitutively expressed in rat brain and the mRNA
      and protein are localized predominantly in neuronal cell population in the
      olfactory bulb, cortex, cerebellum, and hippocampus. An alternate spliced
      transcript of CYP2D1 having exon 3 deletion was detected in rat brain but not in
      liver. Deletion of exon 3 causes frame shift and generates a stop codon at 391 bp
      relative to the start codon ATG leading to premature termination of translation.
      Thus, Northern blotting and in situ hybridization represent contributions from
      functional transcripts and alternate spliced variants that do not translate into
      functional protein. Further, the splice variant having partial inclusion of
      intron 6 detected in human brain was not detected in rat brain indicating that
      alternate spliced gene products of P450 enzymes are generated in species-specific
      and tissue-specific manner.

PMID- 15857672
TI  - Expression and activity of l-isoaspartyl methyltransferase decrease in stage
      progression of human astrocytic tumors.
AB  - Protein l-isoaspartyl methyltransferase (PIMT) functions as a repair enzyme that
      acts upon damaged proteins bearing abnormal aspartyl residues. We previously
      reported that PIMT expression and activity are reduced by half in human epileptic
      hippocampus. Here we investigated PIMT regulation in astrocytic tumors, which are
      the most common human brain tumors. PIMT expression and enzyme activity were
      significantly decreased in all grades of human astrocytic tumors. More precisely,
      PIMT levels were significantly lower by 76% in pilocytic astrocytomas (grade I),
      46% in astrocytomas (grade II), 69% in anaplastic astrocytomas (grade III), and a
      marked 80% in glioblastomas (grade IV) as compared to normal brains. RT-PCR
      analysis showed that levels of type I PIMT mRNA were up-regulated while those of
      type II PIMT mRNA were down-regulated in glioblastomas. Furthermore, the reduced
      PIMT levels correlated closely with a decrease in the number of neuron cells in
      astrocytic tumors as assessed by measuring the neuron-specific enolase level.
      Many proteins with abnormal aspartyl residues accumulated in brain tumors and
      some were specific to individual grades of astrocytic tumors. Similar results
      were obtained, either by measuring the reduction in PIMT activity and expression
      or by measuring the formation of abnormal proteins, in an orthotopic rat brain
      tumor model implanted with invasive CNS-1 glioma cells. The novelty of these
      findings was to provide the first evidence for a marked reduction of PIMT
      expression and activity during stage progression of astrocytic tumors in humans.

PMID- 15857673
TI  - Differential expression of NMDA receptor subunits and splice variants among the
      CA1, CA3 and dentate gyrus of the adult rat.
AB  - N-Methyl-d-aspartate (NMDA)-type glutamate receptors in the hippocampus are
      important mediators of both memory formation and excitotoxicity. It is thought
      that glutamatergic neurons of the CA1, CA3 and dentate gyrus regions of the
      hippocampus contribute differentially to memory formation and are differentially
      sensitive to excitotoxicity. The subunit and/or splice variant composition of the
      NMDA receptor controls many aspects of receptor function such as ligand affinity,
      calcium permeability and channel kinetics, as well as interactions with
      intracellular anchoring and regulatory proteins. Thus, one possible explanation
      of the differences in NMDA receptor-dependent processes, such as synaptic
      plasticity and excitotoxicity, among the hippocampal sub-regions is that they
      differ in subunit and/or splice variant expression. Here we report that the NMDA
      receptor subunits NR1 and NR2B, along with the four splice variant cassettes of
      the NR1 subunit are differentially expressed in the CA1, CA3 and dentate gyrus of
      the hippocampus. Expression of the AMPA receptor subunits GluR1 and GluR2 also
      differ. These differences may contribute to functional differences, such as with
      excitotoxicity and synaptic plasticity, that exist between the sub-regions of the
      hippocampus.

PMID- 15857674
TI  - Effects of AAV-2-mediated aspartoacylase gene transfer in the tremor rat model of
      Canavan disease.
AB  - The tremor rat is a spontaneous epilepsy model with a seizure phenotype caused by
      a deletion in the aspartoacylase (ASPA) gene. The absence of ASPA expression in
      these animals results in undetectable levels of enzyme activity and the
      accumulation of the substrate N-acetyl-aspartate (NAA) in brain, leading to
      generalized myelin vacuolation and severe motor and cognitive impairment. In
      support of human gene therapy for CD, recombinant adeno-associated viral vector
      (AAV-2) expressing ASPA was stereotactically delivered to the tremor rat brain
      and effects on the mutant phenotype were measured. AAV-ASPA gene transfer
      resulted in elevated aspartoacylase bioactivity compared to untreated mutant
      animals and elicited a significant decrease in the pathologically elevated whole
      brain NAA levels. Assessment of motor function via quantitative rotorod testing
      demonstrated that rats injected with AAV-ASPA significantly improved on tests of
      balance and coordinated locomotion compared to animals receiving control vectors.
      This study provides evidence that AAV-2-mediated aspartoacylase gene transfer to
      the brain improves biochemical and behavioral deficits in tremor rat mutants
      (tm/tm) and supports the rationale of human gene transfer for Canavan disease.

PMID- 15857675
TI  - Tissue transglutaminase during mouse central nervous system development: lack of
      alternative RNA processing and implications for its role(s) in murine models of
      neurotrauma and neurodegeneration.
AB  - Tissue transglutaminase (tTG) is a member of a multigene family principally
      involved in catalyzing the formation of protein cross-links. Unlike other members
      of the transglutaminase family, tTG is multifunctional since it also serves as a
      guanosine triphosphate (GTP) binding protein (Galpha(h)) and participates in cell
      adhesion. Different isoforms of tTG can be produced by proteolysis or alternative
      splicing. We find that tTG mRNA is expressed at low levels in the mouse CNS
      relative to other tissues, and at lower levels in the CNS of mouse in comparison
      to that of human or rat. tTG mRNA levels are higher in the heart compared to the
      CNS, for example, and much higher in the liver. Within the CNS, tTG message is
      lowest in the adult cerebellum and thalamus and highest in the frontal cortex and
      striatum. In the hippocampus, tTG expression is highest during embryonic
      development and falls off dramatically after 1 week of life. We did not find
      alternative splicing of the mouse tTG. At the protein level, the predominant
      isoform is approximately 62 kDa. In summary, tTG, an important factor in neuronal
      survival, is expressed at low levels in the mouse CNS and, unlike rat and human
      tTG, does not appear to be regulated by alternative splicing. These findings have
      implications for analyses of rodent tTG expression in human neurodegenerative and
      neurotrauma models where alternative processing may be an attractive pathogenetic
      mechanism. They further impact on drug discovery paradigms, where modulation of
      activity may have therapeutic value.

PMID- 15857676
TI  - Candesartan prevents angiotensin II-induced facilitation of hypoxic neuronal
      damage through PKCdelta inhibition.
AB  - To investigate the role of protein kinase Cdelta (PKCdelta) in angiotensin II
      induced facilitation mechanisms of hypoxic neuronal damage and whether
      candesartan, an AT1 receptor antagonist, can suppress these mechanisms, we
      performed in vitro experiments which were free from vascular components using
      PC12 cells under hypoxic (12 h)/reoxygenation (0-48 h) conditions. Angiotensin II
      apparently increased the basal expression level of PKCdelta phosphorylated at
      Ser(643) before hypoxia, promoted the cleavage of PKCdelta to its catalytic
      fragment, and fostered the progression of DNA fragmentation after hypoxia.
      Candesartan inhibited both phosphorylation and cleavage of PKCdelta and
      suppressed the angiotensin II-induced facilitation of DNA fragmentation under
      hypoxic/reoxygenation conditions. However, PD123319, an AT2 receptor antagonist,
      influenced neither PKCdelta nor the angiotensin II-induced facilitation of DNA
      fragmentation. Furthermore, in PC12 cells expressing the ATP-binding mutant of
      PKCdelta (PKCdelta(K376R)) acting as a dominant-negative protein, both
      phosphorylation and cleavage of PKCdelta were attenuated and DNA fragmentation
      was markedly suppressed regardless of the presence of angiotensin II. These
      findings suggest that angiotensin II-induced facilitation of DNA fragmentation
      under hypoxic conditions is mediated by PKCdelta, and the mechanisms can be
      suppressed by the candesartan mediated blockade of the AT1 receptor.

PMID- 15857677
TI  - The effects of aging on different C-terminal splice forms of the zeta1(NR1)
      subunit of the N-methyl-d-aspartate receptor in mice.
AB  - Changes in NMDA receptors in the prefrontal/frontal cortex and hippocampus of
      C57BL/6 mice during aging show a relationship to declines in spatial learning.
      The present study was designed to determine whether aging influences the mRNA
      expression of different splice forms of the zeta1 subunit of the NMDA receptor.
      We examined the mRNA of 4 C-terminal splice forms with the use of in situ
      hybridization. The zeta1-1 splice form (+C1 and +C2 cassettes) overall showed a
      maintenance of mRNA density from 3 to 10 months of age, followed by a significant
      decline by 26 months of age. In contrast, the mRNA for the zeta1-3 splice form
      [+C1 and +C2'(-C2)] showed significant declines between 3- and 10-month-old mice.
      These declines were maintained in the old mice. The zeta1-2 splice form (-C1 and
      +C2) showed a near-significant decrease in expression during aging across all
      brain regions. The zeta1-4 subunit mRNA [-C1 and +C2' (-C2)] showed no
      significant changes with increased age. These results indicate that there is a
      differential effect of aging on different splice variants of the zeta1 subunit of
      the NMDA receptor and those that are affected show a different temporal pattern
      of aging. This heterogeneity has implications for producing imbalances in the
      modulation of the remaining receptors.

PMID- 15857678
TI  - Differential expression of dopamine D2 and D4 receptor and tyrosine hydroxylase
      mRNA in mice prone, or resistant, to chronic high-fat diet-induced obesity.
AB  - The present study examined brain dopamine D2 and D4 receptor and tyrosine
      hydroxylase (TH) mRNA expression in chronic high-fat diet-induced obese (cDIO)
      and obese-resistant (cDR) mice. Twenty-eight mice were fed a high-fat diet (HF:
      40% of calories from fat) for 6 weeks and then classified as cDIO (n = 8) or cDR
      (n = 8) mice according to the highest and lowest body weight gainers,
      respectively. Seven mice were fed a low-fat diet (LF: 10% of calories from fat)
      and used as controls. After 20 weeks of feeding, visceral fat per gram of initial
      body weight was significantly higher in the cDIO group (ratio: 0.25, 0.09, and
      0.04; P < 0.01 cDIO vs. cDR and LF, respectively). Using quantitative in situ
      hybridization techniques, the levels of D2 and D4 receptor and tyrosine
      hydroxylase (TH) mRNAs were measured in multiple brain sections. The cDIO mice
      had a significantly higher level of D2 receptor mRNA expression in the core of
      the nucleus accumbens (AcbC, +16%) and ventral parts of caudate putamen (CPu, 21%
      and 24%) compared to the cDR and LF mice. The levels of D2 receptor mRNA
      expression in the AcbC and ventromedial part of the CPu were positively related
      to the final body weight. This study is the first to systematically examine the
      D4 mRNA expression in the mouse brain using in situ hybridization method. D4
      receptor mRNA expression in the ventromedial hypothalamic nucleus (VMH) and the
      ventral part of the lateral septal nucleus were also significantly higher in the
      cDIO mice compared to the cDR and LF mice (+31% and +60%; P < 0.05). TH mRNA
      expression was significantly higher in the ventral tegmental area (+17%, P </=
      0.05) and locus caeruleus (+15%, P </= 0.05) of the cDIO mice compared to cDR
      mice. In conclusion, this study has demonstrated differentially regulated levels
      of D2 and D4 receptor and TH mRNA expression in specific brain regions of cDIO
      and cDR mice. It provides evidence that D4 receptors may play an important role
      influencing satiety via the mesohypothalamic pathway while the D2 receptor may
      regulate reward and motor centers via mesolimbic and nigrostriatal pathways.
      These findings contribute to the understanding of the role of these receptors in
      susceptibility, or resistance, to diet-induced obesity.

PMID- 15857679
TI  - Expression and distribution of vanilloid receptor 1 (TRPV1) in the adult rat
      brain.
AB  - The vanilloid receptor (TRPV1 or VR1) is a molecular integrator of various
      painful stimuli, including capsaicin, acid, and high temperature. It can also be
      activated by endogenous ligands, like the cannabinoid 1 receptor (CB1) agonist
      anandamide. TRPV1 is well characterized at the terminals of sensory nerves
      involved in the pain pathway. There is also evidence that TRPV1 is expressed in
      the brain but little is known about its function. Here, using commercially
      available specific antibodies to investigate the localization of TRPV1 in the
      brain of the rat, we report that TRPV1 was expressed in hippocampus, cortex,
      cerebellum, olfactory bulb, mesencephalon and hindbrain. Immunohistochemical
      analyses showed high expression in the cell bodies and dendrites of neurons in
      the hippocampus and in the cortex. To address the question of subcellular
      localization, immunoelectronmicroscopy was used. TRPV1-like staining was detected
      in the synapses (mostly, but not exclusively in post-synaptic dendritic spines),
      on the end feet of astrocytes and in pericytes. In summary, TRPV1 expression
      shows wide distribution in the brain of the rat, being found in astrocytes and
      pericytes as well as in neurons. Its localization is consistent with multiple
      functions within the central nervous system, including the regulation of brain
      vasculature.

PMID- 15857680
TI  - Identification and differential expression of multiple isoforms of mouse Coiled
      coil-DIX1 (Ccd1), a positive regulator of Wnt signaling.
AB  - The Wnt signaling plays important roles in cell growth, differentiation, polarity
      formation, and neural development. In the canonical pathway, two DIX domain
      containing proteins, Dishevelled (Dvl) and Axin, regulate the degradation of beta
      catenin that activates Wnt target genes through TCF/LEF family transcription
      factors. Recently, we have isolated a third type of DIX domain-possessing
      protein, Coiled-coil-DIX1 (Ccd1). Ccd1 forms homomeric and heteromeric complexes
      with Dvl and Axin, and regulates the neural patterning in zebrafish embryos
      through Wnt pathway activation. Here, we report the isolation and
      characterization of mouse Ccd1. Fourteen putative mRNA isoforms are generated by
      different promoter usage and alternative splicing, and each isoform shows
      different expression patterns in various tissues. The predicted Ccd1 proteins are
      classified into three subtypes, and a novel form, termed Ccd1A, possesses an N
      terminal calponin homology domain, suggesting an additional interaction of the
      isoform with actin or other proteins. When Ccd1 proteins were singularly
      expressed in Hela cells, they showed almost no activation of TCF-dependent
      reporter transcription on their own. However, when Dvl protein, at the level that
      did not activate Wnt pathway by itself, was co-expressed with Ccd1, the reporter
      transcription was greatly potentiated in Ccd1-dose-dependent manner. In addition,
      Ccd1- and Wnt3a-dependent activation of Wnt pathway was inhibited by Axin or a
      dominant negative Ccd1. These results indicate that mouse Ccd1 functions as a
      positive regulator of the Wnt/beta-catenin pathway. Furthermore, Ccd1 is highly
      expressed and co-localized with Wnt signaling molecules in the embryonic and
      adult brain, implicating the importance of Ccd1 in the Wnt-mediated neuronal
      development, plasticity, and remodeling.

PMID- 15857681
TI  - Exercise activates the phosphatidylinositol 3-kinase pathway.
AB  - Physical exercise is known to enhance psychological well-being and coping
      capacity. Voluntary physical exercise in rats also robustly and rapidly up
      regulates hippocampal brain-derived neurotrophic factor (BDNF) mRNA levels, which
      are potentiated following a regimen of chronic antidepressant treatment.
      Increased BDNF levels are associated with enhanced activity of cyclic AMP
      response element binding protein (CREB). So far, relatively little is known about
      the intracellular signaling mechanisms mediating this effect of exercise. We
      wished to explore the possibility that exercise and/or antidepressant treatment
      activate the hippocampal phosphatidylinositol-3 (PI-3) kinase pathway, which
      mediates cellular survival. In young male Sprague-Dawley rats, we examined the
      effects of 2 weeks of daily voluntary wheel-running activity and/or
      tranylcypromine (n = 7 per group) on the levels of the active forms of protein
      dependent kinase-1 (PDK-1), PI-3 kinase, phospho-thr308-Akt, phospho-ser473-Akt,
      and phospho-glycogen synthase kinase-3beta (GSK3beta; inactive form), as well as
      BDNF, activated CREB, and the phospho-Trk receptor, in the rat hippocampus, and
      compared these with sedentary saline-treated controls. Immunoblotting analyses
      revealed that in exercising rats, there was a significant increase in PI-3 kinase
      expression (4.61 times that of controls, P = 0.0161) and phosphorylation of PDK-1
      (2.73 times that of controls, P = 0.0454), thr308-Akt (2.857 times that of
      controls, P = 0.0082), CREB (60.27 times that of controls, P = 0.05), and Trk
      (35.3 times that of controls, P < 0.0001) in the hippocampi of exercising
      animals; BDNF was also increased (3.2 times that of controls), but this was not
      statistically significant. In rats receiving both exercise and tranylcypromine,
      BDNF (4.51 times that of controls, P = 0.0068) and PI-3 kinase (4.88 times that
      of controls, P = 0.0103), and the phospho- forms of Trk (13.67 times that of
      controls, P = 0.0278), thr308-Akt (3.644 times that of controls, P = 0.0004), GSK
      3beta (2.93 times that of controls, P = 0.026), and CREB (88.97 times that of
      controls, P = 0.0053) were significantly increased. These results suggest that
      the exercise-induced expression of BDNF is associated with the increased
      expression of several key intermediates of the PI-3 kinase/Akt pathway, which is
      known for its role in enhancing neuronal survival.

PMID- 15857682
TI  - A second tryptophan hydroxylase isoform, TPH-2 mRNA, is increased by ovarian
      steroids in the raphe region of macaques.
AB  - Recently, a second gene that codes for the rate-limiting enzyme in serotonin
      synthesis was found in brain, named tryptophan hydroxylase-2 (TPH-2). We
      sequenced overlapping segments (251 and 510 bp) of 5' monkey TPH-2 and questioned
      whether TPH-2 is regulated by estrogen (E) and progesterone (P) in serotonin
      neurons of macaques. Monkey TPH-2 was 97% homologous to human TPH-2 and 65%
      homologous to monkey TPH-1 in the coding region. Spayed monkeys were administered
      placebo, E-only, P-only, or E + P for 1 month via Silastic implants (n =
      4/treatment) and the midbrain was utilized for TPH-2 in situ hybridization (ISH).
      Additional monkeys (n = 3/treatment) were used to determine the relative
      abundance of TPH-2 mRNA with quantitative (q) RT-PCR. In the ISH assay, all of
      the hormone treatments caused a significant and similar increase in TPH-2 mRNA
      optical density (fourfold; P < 0.004) and positive pixel area (twofold; P <
      0.002) over spayed controls. Treatment with E or E + P for 1 month increased the
      relative abundance of TPH-2 mRNA over spayed controls in the qRT-PCR assay (ANOVA
      P < 0.05 and P < 0.007, respectively). In conclusion, ovarian steroids stimulate
      TPH-2 mRNA expression, which could in turn cause an increase in serotonin
      synthesis. This would impact many of the neural functions that are governed by
      serotonin.

PMID- 15857683
TI  - p55 protein is a member of PSD scaffold proteins in the rat brain and interacts
      with various PSD proteins.
AB  - p55 is a membrane-associated guanylate kinase (MAGuK) family member that consists
      of a single PDZ followed by SH3, HOOK and guanylate kinase (GuK or GK) domains.
      We investigated rat p55 (r-p55) in the brain. r-p55 mRNA was expressed widely in
      various tissues and in various regions of the brain. r-p55 protein was also
      expressed widely in various rat tissues, including brain and erythrocytes. The
      protein was enriched in the synaptic plasma membrane and postsynaptic density
      (PSD) fractions of the forebrain. An immunocytochemical study using cultured
      cortical neurons suggested postsynaptic localization of r-p55 protein. Pull-down
      assay showed that r-p55 protein interacted with r-p55 itself and various PSD
      proteins, such as PSD-95, SAP97, GKAP, CASK, GRIP, neuroligin, cadherin, tubulin,
      actin, alpha-internexin, neurofilament-L and Ca(2+)/calmodulin-dependent protein
      kinase II, through its PDZ, SH3, HOOK or GK domains. The interaction with PSD-95
      was found to occur between the PDZ domains of PSD-95 and the HOOK and GK domains
      of r-p55 protein. These findings, together with the presence of r-p55 puncta in a
      period of early synaptogenesis, suggest that r-p55 protein functions as one of
      postsynaptic scaffold component in an early stage of synaptogenesis in the brain.
      r-p55 protein may form a basic structure, which interlinks diverse functional
      molecules of the PSD necessary for postsynaptic signaling and synaptic adhesion.

PMID- 15857684
TI  - Biochemical demonstration of mu-opioid receptor association with Gsalpha:
      enhancement following morphine exposure.
AB  - Biochemical data indicate mu-opioid receptor (MOR) coupling predominantly to the
      G(i) and G(o) family. Additionally, MOR coupling to G(s) is suggested by
      pharmacological assessments that have revealed excitatory MOR effects, which are
      resistant to pertussis toxin and sensitive to cholera toxin. However, biochemical
      evidence for such interactions remains elusive; G(salpha) has not been shown to
      be present in immunoprecipitate obtained using anti-MOR antibodies. In the
      current study, the presence of MOR in immunoprecipitate obtained with anti
      G(salpha ) antibodies was investigated using Chinese hamster ovary cells stably
      transfected with MOR (MOR-CHO). MOR Western analyses of opioid naive MOR-CHO
      membranes immunoprecipitated using anti-G(salpha) antibodies reveal the presence
      of an approximately 75-80 kDa MOR species. Interestingly, acute and chronic
      morphine treatment markedly enhances the magnitude of MOR that co
      immunoprecipitates with G(salpha), despite the concomitant down-regulation of
      membrane MOR protein. Enhanced co-precipitation of MOR with G(salpha) occurs
      without a concomitant increase in the immunoprecipitated G(salpha) protein
      indicating their increased association. In contrast, chronic morphine diminishes
      the co-immunoprecipitation of MOR with G(ialpha). Moreover, although only a
      single MOR species co-immunoprecipitated with G(salpha), MOR Western analysis of
      MOR-CHO membranes as well as immunoprecipitate obtained with either anti-MOR or
      anti-G(ialpha) antibodies reveals the presence of multiple molecular mass species
      of MOR. These data reveal the existence of a subset of MORs whose association
      with G(salpha) can be enhanced by morphine exposure. Notably, the regulation by
      chronic morphine of MOR association with G(salpha) and G(ialpha) is reciprocal.
      The relevance of MOR-Gs(alpha) coupling to opioid tolerance formation is
      discussed.

PMID- 15857685
TI  - Expression of Catenin family members CTNNA1, CTNNA2, CTNNB1 and JUP in the
      primate prefrontal cortex and hippocampus.
AB  - Members of the catenin family of proteins are thought to play a major role in the
      folding and lamination of the cerebral cortex. We have used in situ hybridization
      to determine the cellular expression patterns of four members of this family,
      Alpha-E-, Alpha-N-, Beta-, and Gamma-catenins (CTNNA1, CTNNA2, CTNNB1, and JUP
      respectively) in the adult primate dorsolateral prefrontal cortex (DLPFC) and
      hippocampus. CTNNA2, CTNNB1, and JUP mRNAs were detected in all layers of the
      DLPFC and in all neuronal subregions of the hippocampal formation, however CTNNA1
      mRNA, coding for an 'epithelial' specific catenin, was not detected in any region
      of the cortex or hippocampus. CTNNA2, a 'neuronal-specific' catenin, and CTNNB1
      mRNAs were abundant in both DLPFC and hippocampus, with a distinct neuronal
      localization. CTNNA2 mRNA was concentrated in both granular/stellate cells and
      large pyramidal cell bodies, while CTNNB1 expression was more strongly associated
      with granular cell bodies throughout the DLPFC, with expression in pyramidal
      cells confined mainly to cortical Layers III and VI. CTNNA2 and CTNNB1 mRNAs were
      also abundant in the granule cells of the dentate gyrus and pyramidal cells of
      Ammon's horn, apparently co-expressed in the same neurons. JUP mRNA was rather
      diffusely localized in the DLPFC without the distinct laminar patterns seen for
      CTNNA2 and CTNNB1 but was distinctly localized in the granule cells of the
      dentate gyrus and pyramidal cells of Ammon's horn. These studies demonstrate a
      distinct neuronal pattern of gene expression for catenin family members in
      primate brain structures characterized by high degrees of folding and strong
      lamination. The high level expression of these transcripts supports the notion of
      a major role for catenins even in the adult brain. Such an understanding is also
      important in view of the multiple interactions that catenins have with many other
      proteins in the adult and ageing brain. This may also have implications for
      understanding the pathogenesis of neurodegenerative diseases such as Alzheimer's
      disease, as well as emerging neuronal stem cell therapies.

PMID- 15857686
TI  - Postsynaptic IP3 receptor-mediated Ca2+ release modulates synaptic transmission
      in hippocampal neurons.
AB  - Ca(2+)-dependent mechanisms are important in regulating synaptic transmission.
      The results herein indicate that whole-cell perfusion of inositol 1,4,5
      trisphosphate receptor (IP(3)R) agonists greatly enhanced excitatory postsynaptic
      current (EPSC) amplitudes in postsynaptic hippocampal CA1 neurons. IP(3)R agonist
      mediated increases in synaptic transmission changed during development and
      paralleled age-dependent increases in hippocampal type-1 IP(3)Rs. IP(3)R agonist
      mediated increases in EPSC amplitudes were inhibited by postsynaptic perfusion of
      inhibitors of Ca(2+)/calmodulin, PKC and Ca(2+)/calmodulin-dependent protein
      kinase II. Postsynaptic perfusion of inhibitors of smooth endoplasmic reticulum
      (SER) Ca(2+)-ATPases, which deplete intracellular Ca(2+) stores, also enhanced
      EPSC amplitudes. Postsynaptic perfusion of the IP(3)R agonist adenophostin (AdA)
      during subthreshold stimulation appeared to convert silent to active synapses;
      synaptic transmission at these active synapses was completely blocked by 6-cyano
      7-nitroquinoxaline-2,3-dione (CNQX). Postsynaptic IP(3)R-mediated Ca(2+) release
      also produced a significant increase in spontaneous EPSC frequency. These results
      indicate that Ca(2+) release from intracellular stores play a key role in
      regulating the function of postsynaptic AMPARs.

PMID- 15857688
TI  - Modulation of GABA receptor subunits in rat facial motoneurons after axotomy.
AB  - Facial nerve axotomy is a good model for studying neuronal plasticity and
      regeneration in the peripheral nervous system. In the present study, we
      investigated the effect of axotomy on the different subunits of GABA(A) and
      GABA(B) receptors of facial motoneurons. The facial nerve trunk was unilaterally
      sectioned and operated rats were sacrificed at 1, 3, 8, 30, and 60 days later.
      mRNAs coding for alpha1, beta2, and gamma2 of GABA(A) receptors and for GABA(1B)
      and GABA(B2) receptors were down-regulated by axotomy. This decrease began as
      soon as 1 or 3 days after axotomy, and the minimum was 8 days post-lesion; the
      mRNA levels remained lower than normal at day post-lesion 60. The abundance of
      mRNAs coding for the three other alpha2, beta1, and beta3 facial subunits of
      GABA(A) receptors and for the pre-synaptic GABA(B1A) subunit remained unchanged
      during the period 1-8 days post-lesion. Immunohistochemistry using specific
      antibodies against alpha1, gamma2 subunits of GABA(A) and against GABA(B2)
      subunits confirmed this down-regulation. Colchicine treatment and blockade of
      action potential by tetrodotoxin significantly decreased GABA(A)alpha1
      immunoreactivity in the axotomized facial nucleus after 7 days. Finally, muscle
      destruction by cardiotoxin or facial palsy induced by botulinum toxin failed to
      change GABA(A)alpha1 subunit expression. Our data demonstrate that axotomy
      strongly reduced the amounts of alpha1, beta2, and gamma2 subunits of GABA(A)
      receptors and B(1B) and B(2) subunits of GABA(B) receptors in the axotomized
      facial motoneurons. The loss of GABA(A)alpha1 subunit was most probably induced
      by both the loss of trophic factors transported from the periphery and a positive
      injury signal. It also seems to be dependent on activity disruption.

PMID- 15857687
TI  - Role of NRSF/REST in the molecular mechanisms regulating neural-specific
      expression of trkC/neurotrophin-3 receptor gene.
AB  - The processes of differentiation and development of neurons involve the induction
      of neuron-specific genes by instructive signals with subsequent neurotrophic
      factor-driven survival and functional maturation. We have previously shown that
      bone morphogenetic protein-2 (BMP2) and retinoic acid synergistically induce the
      responsiveness of developing sympathetic neurons to neurotrophic factors,
      neurotrophin 3 (NT-3), and GDNF by upregulating corresponding receptors
      concomitantly with the induction of other neuron-specific genes including BRINP1,
      a neuron-specific cell-cycle regulatory protein. In the present study, we
      analyzed transcriptional mechanisms regulating the neuron-specific expression of
      TrkC/NT-3 receptor gene. TrkC gene contains at least four NRSE/RE-1 (neuron
      restrictive silencing element/repressor element 1)-like elements (TrkC-NRSE A-D).
      Consequently, we found that in non-neuronal cells, neuron-restrictive silencing
      factor (NRSF) acts on TrkC-NRSE D located at the downstream of exon 3 to suppress
      the promoter activity of TrkC gene in a manner similar to the mechanism of NRSF
      suppressing BRINP1 transcription. In contrast, in neuronal cells, the biological
      activity of NRSF on TrkC was suppressed. From these observations, molecular
      mechanisms regulating the expression of neuron-specific genes via NRSE during
      neuronal differentiation are discussed.

PMID- 15857689
TI  - Overexpression of the mineralocorticoid receptor protects against injury in PC12
      cells.
AB  - Mineralocorticoid receptor expression is increased following neuronal injury, and
      this is associated with increased neuronal survival. Here we demonstrate a causal
      link between overexpression of MR in PC12 cells and protection against death
      induced by staurosporine and oxygen-glucose deprivation. This survival effect is
      abrogated by MR antagonism. Drugs which upregulate MR may form the basis for a
      novel therapeutic approach in conditions such as stroke and head injury.

PMID- 15857690
TI  - Increased expression of L-type high voltage-gated calcium channel alpha1 and
      alpha2/delta subunits in mouse brain after chronic nicotine administration.
AB  - We investigated the effect of chronic nicotine administration on high voltage
      gated calcium channels (HVCCs) in the mouse cerebral cortex. The treatment
      significantly increased expression of alpha1C, alpha1D, alpha1F, and
      alpha2/delta1 subunits with no changes of beta4 subunit of L-type HVCCs.
      [(3)H]Diltiazem binding to the particulate fractions increased with increased
      Bmax value. These results indicate that chronic nicotine treatment up-regulates L
      type HVCCs, which is due to increased expression of alpha1 and alpha2/delta1
      subunits.

PMID- 15857691
TI  - Valproic acid, but not lamotrigine, suppresses seizure-induced c-fos and c-Jun
      mRNA expression.
AB  - Seizure-induced activity has been shown to increase the expression of immediate
      early genes (IEGs) c-fos and c-Jun in the CNS. Anti-epileptic drugs (AEDs) can
      suppress the induction of a seizure, but it is unknown if AEDs affect the
      expression of seizure-induced IEGs. We found that valproic acid (VPA), but not
      lamotrigine (LTG), was capable of suppressing seizure-induced c-fos and c-Jun
      mRNA expression in rats despite a similar anticonvulsant effect. LTG in some
      regions of the CNS enhanced seizure-induced IEG expression. These studies
      indicate that the older AED (VPA), as compared to the newer AED (LTG), can
      suppress seizure-induced IEG expression. The consequence of this suppression of
      IEGs following a generalized seizure may be viewed either as a neuroprotective or
      detrimental effect upon the brain.

PMID- 15857692
TI  - Decrease of kappa-opioid receptor mRNA level in ventral tegmental area of male
      mice after repeated experience of aggression.
AB  - Brain opioid systems have been implicated in the regulation of social
      interaction, including agonistic behaviour. kappa-Opioid receptor B and C mRNA
      levels were decreased in the ventral tegmental area but not in the nucleus
      accumbens in male mice with repeated experience of social victories (winners),
      but not in mice after social defeats (losers) after 10 but not 20 days of
      confrontations. mu-Opioid receptor mRNA levels were not changed.

PMID- 15857693
TI  - Gene expression profiling in hypothalamus of immobilization-stressed mouse using
      cDNA microarray.
AB  - To investigate the effects of repeated immobilization-stress challenge on HPA
      axis, genomic transcriptome in the hypothalamus of immobilization-stressed mouse
      was analyzed by using cDNA microarray. With the 1.5-fold cutoff of arbitrary
      criteria, the expression levels of 108 genes out of 6016 genes were significantly
      modulated in the hypothalamus by the stress. Energy metabolism-, lipid metabolism
      , and apoptosis- and signal transduction-related genes were activated while DNA
      repair-, protein biosynthesis-, and structure integrity-related genes were down
      regulated in the hypothalamus. Eighteen genes among them were selected for RT-PCR
      analysis to confirm the change of their expression levels on agarose gels.
      Besides, dozens of novel genes, which have not been previously reported, were
      screened to be modulated by the immobilization stress through the transcriptome
      analysis. These genes are related to apoptosis, tumor-suppression, DNA-binding
      and protein folding, and thus may be used as potential targets for the
      development of therapeutics of chronic stress or depressant.

PMID- 15857694
TI  - A quantitative in situ hybridization and polymerase chain reaction study of
      microglial-macrophage expression of interleukin-1beta mRNA following permanent
      middle cerebral artery occlusion in mice.
AB  - Interleukin-1beta (IL-1beta) is known to play a central role in ischemia-induced
      brain damage in rodents. In comparison to the rat, however, the available data on
      the cellular synthesis of IL-1beta mRNA and protein in the mouse are very
      limited. Here, we report on the time profile, the topography and the
      quantitative, cellular expression of IL-1beta mRNA in mice subjected to permanent
      occlusion of the distal middle cerebral artery (MCA). The in situ hybridization
      analysis showed that IL-1beta mRNA was expressed during the first post-surgical
      hour in a small number of high-expressing macrophage-like cells, located in
      cortical layers I and II of the future infarct. At 2 h, a significant number of
      faintly labeled IL-1beta mRNA-expressing cells had appeared in the developing
      peri-infarct, and the number remained constant at 4 h and 6 h, when the
      hybridization signal began to distribute to the cellular processes. Quantitative
      PCR performed on whole hemispheres showed a significant 20-fold increase in the
      relative level of IL-1beta mRNA at 12 h and a highly significant 42-fold increase
      at 24 h, at which time single IL-1beta mRNA-expressing cells were supplemented by
      aggregates and perivascular infiltrates of intensely labeled IL-1beta mRNA
      expressing cells. Immunohistochemistry and double immunohistochemical stainings
      in addition to combined in situ hybridization, confirmed that the intensely
      labeled IL-1beta mRNA-expressing and IL-1beta protein synthesizing cells
      predominantly were glial fibrillary acidic protein-immunonegative, macrophage
      associated antigen-1-immunopositive microglia-macrophages. By day 5 there was a
      dramatic decline in the relative level of IL-1beta mRNA in the ischemic
      hemisphere. In summary, the data provide evidence that permanent occlusion of the
      distal MCA in mice results in expression of IL-1beta mRNA and IL-1beta synthesis
      in spatially and temporally segregated subpopulations of microglia and
      macrophages.

PMID- 15857695
TI  - Different synaptic and subsynaptic localization of adenosine A2A receptors in the
      hippocampus and striatum of the rat.
AB  - Adenosine A(2A) receptors are most abundant in the striatum where they control
      the striatopallidal pathway thus controlling locomotion. Extra-striatal A(2A)
      receptors are considerably less abundant but their blockade confers robust
      neuroprotection. We now have investigated if striatal and extra-striatal A(2A)
      receptors have a different neuronal location to understand their different
      functions. The binding density of the A(2A) antagonist, [(3)H]-7-(2-phenylethyl)
      5-amino-2-(2-furyl)pyrazolo[4,3e][1,2,4]triazolo[1,5-c]pyrimidine ([(3)H]SCH
      58261), was enriched in nerve terminals membranes (B(max)=103+/-12 fmol/mg
      protein) compared with total membranes (B(max)=29+/-4 fmol/mg protein) from the
      hippocampus, the same occurring with A(2A) receptor immunoreactivity. In
      contrast, there was no enrichment of [(3)H]SCH 58261 binding or A(2A) receptor
      immunoreactivity in synaptosomal compared with total membranes from the striatum.
      Further subcellular fractionation of hippocampal nerve terminals revealed that
      A(2A) receptor immunoreactivity was enriched in the active zone of presynaptic
      nerve terminals, whereas it was predominantly located in the postsynaptic density
      in the striatum, although a minority of striatal A(2A) receptors were located in
      the presynaptic active zone. These results indicate that A(2A) receptors in the
      striatum are not enriched in synapses in agreement with the preponderant role of
      A(2A) receptors in signal processing in striatopallidal neurons. In contrast,
      hippocampal A(2A) receptors are enriched in synapses, mainly in the active zone,
      in accordance with their role in controlling neurotransmitter release. This
      regional variation in the neuronal distribution of A(2A) receptors reinforces the
      care required to extrapolate our knowledge from striatal A(2A) receptors to other
      brain preparations.

PMID- 15857696
TI  - Imbalance between the expression of NK1 and GABAB receptors in nociceptive spinal
      neurons during secondary hyperalgesia: a c-Fos study in the monoarthritic rat.
AB  - The neurochemical changes that operate in nociceptive spinal cord circuits during
      secondary hyperalgesia are largely unknown, in particular with respect to the
      balance between excitatory and inhibitory neurotransmission. In this study we
      evaluated the expression of NK1 and GABA(B) receptors in nociceptive spinal
      neurons in a model of secondary hyperalgesia consisting of noxious mechanical
      stimulation of the hindlimb skin close to a joint chronically inflamed by
      complete Freund's adjuvant. In spinal segments receiving input from that skin
      area, Fos-immunodetection was combined with immunocytochemistry for NK1
      receptors, GABA(B) receptors or both receptors. In control and monoarthritic
      animals, neurons double-labeled for Fos and each receptor occurred mainly in
      laminae I and IV-V. In lamina I, the percentage of NK1 neurons expressing Fos was
      higher in monoarthritics while lower percentages of GABA(B) neurons expressed
      Fos. The percentage of Fos-positive cells expressing NK1 immunoreaction did not
      change in monoarthritics but that of Fos cells with GABA(B) immunoreaction was
      lower in these animals. In laminae IV-V, a large increase in Fos expression was
      detected in monoarthritic rats but the relative proportions of Fos-positive
      neurons expressing each receptor were similar in the two groups. Co-localization
      of NK1 and GABA(B) receptors occurred only in lamina I neurons in both
      experimental groups with no differences between control and monoarthritic animals
      in the percentages of Fos-positive neurons that expressed the receptors.
      Considering the participation of lamina I neurons bearing NK1 and GABA(B)
      receptors in several spinofugal systems, it is possible that the imbalance
      between excitatory and inhibitory actions exerted, respectively, by substance P
      and GABA may subserve secondary hyperalgesia by increasing ascending transmission
      of nociceptive input.

PMID- 15857697
TI  - Critical period for activity-dependent elimination of corticospinal synapses in
      vitro.
AB  - There is no in vitro model of the critical periods for developmental plasticity,
      the time windows of plastic changes during development, which may hinder in-depth
      mechanistic analysis. We have shown previously that the corticospinal tract with
      synaptic connections can be reconstructed in in vitro co-cultures using slices of
      the sensorimotor cortex and spinal cord of the rat. In our in vitro system,
      corticospinal synapses form widely over spinal gray matter during early
      development, after which those on the ventral side are eliminated in an activity
      and N-methyl-D-aspartate (NMDA)-dependent manner. A detailed quantitative
      analysis of the time course of sensitivity to an NMDA blocker was made with this
      system. Synapse distribution was evaluated by recording field excitatory post
      synaptic potentials evoked by deep cortical layer stimulation. Corticospinal axon
      terminal distribution was examined by anterograde labeling with biocytin. We
      showed that the D-2-amino-5-phosphonovaleric acid (APV) effect is irreversible
      for at least the length of culture. When APV was removed from the medium before 6
      days in vitro(DIV) or after 11 DIV, elimination of ventral synapses was not
      blocked. APV sensitivity showed a clearly defined time window. A 6-11 DIV
      application was necessary and sufficient for the full, irreversible block of
      synapse elimination. From 6-11 DIV, APV sensitivity seems to decrease gradually
      but not linearly. This system provides an in vitro model of critical periods for
      developmental plasticity of central synapses which up to now has not been
      available.

PMID- 15857698
TI  - Difficulty of perceptual spatiotemporal integration modulates the neural activity
      of left inferior parietal cortex.
AB  - The integration of spatial and temporal information is a prerequisite for skilled
      movements. Likewise, spatial and temporal information must be integrated to
      predict the potential collision (or otherwise) of two moving objects. In a
      previous blocked functional magnetic resonance imaging (fMRI) study [Neuroimage
      20 (2003) S82] we showed that collision judgments (relative to size judgments)
      provoked a significant increase in neural activity in the left inferior parietal
      cortex (supramarginal gyrus). This result suggests that this region is involved
      in the integration of perceptual spatiotemporal information in addition to its
      known involvement in programming skilled actions. To further investigate the
      impact of the integration of temporal and spatial information on the left
      parietal cortex we conducted an event-related fMRI study in which we varied the
      difficulty of the collision (and the size) judgment tasks parametrically.
      Reaction times and error rates were used as behavioral measures of increasing
      task demands. There was a significant linear increase in reaction times and error
      rates during the collision and the size tasks over the four levels of task
      difficulty. A linear increase of the blood oxygen level-dependent signal in the
      left inferior parietal cortex was found only for the collision, not for the size,
      conditions. Neural activation in the left inferior parietal cortex thus
      paralleled the increasing demands on spatiotemporal integration. This result
      confirms that the left supramarginal gyrus integrates spatial and temporal
      information irrespective of motor demands.

PMID- 15857699
TI  - Changes in secondary glutamate release underlie the developmental regulation of
      excitotoxic neuronal cell death.
AB  - Vulnerability to excitotoxicity increases during development in vivo and in
      vitro. To determine whether the mere presence of mature N-methyl-D-aspartate
      (NMDA) receptors coincides with the emergence of excitotoxicity or whether post
      receptor signaling processes may also contribute, we examined the temporal
      relationship of NMDA receptor expression, function and toxicity using cortical
      cell cultures. Surface expression of all NMDA receptor subunits increased with
      time in culture. This correlated with NMDA receptor function, assessed both
      biochemically and electrophysiologically, but not with the appearance of
      excitotoxicity. Specifically, cells at day in vitro (DIV) 10 were less
      susceptible to NMDA receptor-induced neurotoxicity than those cultured for 14
      days, even though receptor expression/function was identical. In addition, cell
      attached single channel recordings revealed that NMDA receptor conductance, open
      probability, and frequency of channel openings were not significantly different
      between the two days. Intriguingly, depolarization-induced release of glutamate
      from cultures grown for 10 days was significantly lower than that released from
      cultures grown for 14 days. Further, exogenous addition of glutamate receptor
      agonists immediately after removal of NMDA rendered cultures at DIV 10
      susceptible to excitotoxicity, while toxicity was significantly reduced by
      addition of an NMDA receptor antagonist immediately after exposure to NMDA at DIV
      14. These data are the first to demonstrate that the subsequent, secondary
      release of glutamate plays an equal, if not more important, role than NMDA
      receptor development per se, in mediating the enhanced vulnerability of neurons
      to excitotoxicity that occurs with age.

PMID- 15857700
TI  - Infralimbic cortex activation increases c-Fos expression in intercalated neurons
      of the amygdala.
AB  - Recently, it was reported that stimulation of the infralimbic cortex produces a
      feedforward inhibition of central amygdala neurons. The interest of this
      observation comes from the fact that the central nucleus is the main output
      station of the amygdala for conditioned fear responses and evidence that the
      infralimbic cortex plays a critical role in the extinction of conditioned fear.
      However, the identity of the neurons mediating this infralimbic-evoked inhibition
      of the central nucleus remains unknown. Likely candidates are intercalated
      amygdala neurons. Indeed, these cells receive glutamatergic afferents from the
      infralimbic cortex, use GABA as a transmitter, and project to the central
      amygdala. Thus, the present study was undertaken to test whether, in adult rats,
      the infralimbic cortex can affect the activity of intercalated neurons. To this
      end, disinhibition of the infralimbic cortex was induced by local infusion of the
      non-competitive GABA-A receptor antagonist picrotoxin. Subsequently, neuronal
      activation was determined bilaterally within the amygdala using induction of the
      immediate early gene Fos. Infralimbic disinhibition produced a significant
      increase in the number of Fos-immunoreactive intercalated cells bilaterally
      whereas no change was detected in the central nucleus. In the basolateral
      amygdaloid complex, increases in the number of Fos-immunoreactive cells only
      reached significance in the contralateral lateral nucleus. These results suggest
      that glutamatergic inputs from the infralimbic cortex directly activate
      intercalated neurons. Thus, our findings raise the possibility that the
      infralimbic cortex inhibits conditioned fear via the excitation of intercalated
      cells and the consequent inhibition of central amygdala neurons.

PMID- 15857702
TI  - The role of the N-methyl-D-aspartate receptor in ketamine-induced apoptosis in
      rat forebrain culture.
AB  - Recent data suggest that anesthetic drugs may cause widespread and dose-dependent
      apoptotic neurodegeneration during development. The window of vulnerability to
      this neurotoxic effect, particularly with N-methyl-D-aspartate (NMDA) antagonists
      such as ketamine, is restricted to the period of synaptogenesis. The purposes of
      this study are to determine whether treatment of forebrain cultures with ketamine
      results in a dose-related increase in neurotoxicity and whether upregulation of
      NMDA receptor subunit NR1 promotes ketamine-induced apoptosis. Forebrain cultures
      were treated for 12 h with 0.1, 1, 10 and 20 microM ketamine or co-incubated with
      NR1 antisense oligonucleotide (2 microM). After washout of the ketamine, cultures
      were kept in serum-containing medium (in presence of glutamate) for 24 h.
      Application of ketamine (10 and 20 microM) resulted in a substantial increase in
      DNA fragmentation as measured by cell death enzyme-linked immunosorbent assay,
      increased number of terminal dUTP nick-end labeling positive cells, and a
      reduction in mitochondrial metabolism of the dye 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide. No significant effect was seen in the release of
      lactate dehydrogenase, indicating that cell death presumably occurred via an
      apoptotic mechanism. Co-incubation of ketamine with NR1 antisense significantly
      reduced ketamine-induced apoptosis. Western analysis showed that neurotoxic
      concentrations of ketamine increased Bax and NR1 protein levels. NR1 antisense
      prevented this increase caused by ketamine, suggesting that ketamine-induced cell
      death is associated with a compensatory upregulation of the NMDA receptor. These
      data suggest that NR1 antisense offers neuroprotection from apoptosis in vitro,
      and that upregulation of the NR1 following ketamine administration is, at least,
      partially responsible for the observed apoptosis.

PMID- 15857701
TI  - Nociceptin/orphanin FQ (N/OFQ) inhibits excitatory and inhibitory synaptic
      signaling in the suprachiasmatic nucleus (SCN).
AB  - Environmental synchronization of the endogenous mammalian circadian rhythm
      involves glutamatergic and GABAergic neurotransmission within the hypothalamic
      suprachiasmatic nucleus (SCN). The neuropeptide nociceptin/orphanin FQ (N/OFQ)
      inhibits light-induced phase shifts, evokes K(+)-currents and reduces the
      intracellular Ca(2+) concentration in SCN neurons. Since these effects are
      consistent with a modulatory role for N/OFQ on synaptic transmission in the SCN,
      we examined the effects of N/OFQ on evoked and spontaneous excitatory and
      inhibitory currents in the SCN. N/OFQ produced a consistent concentration
      dependent inhibition of glutamate-mediated excitatory postsynaptic currents
      (EPSC) evoked by optic nerve stimulation. N/OFQ did not alter the amplitude of
      currents induced by application of (RS)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) or N-methyl-d-aspartate (NMDA) nor the amplitude
      of miniature EPSC (mEPSC) consistent with a lack of N/OFQ effect on postsynaptic
      AMPA or NMDA receptors. N/OFQ significantly reduced the mEPSC frequency. The
      inhibitory actions of N/OFQ were blocked by omega-conotoxin GVIA, an N-type
      Ca(2+)channel antagonist and partially blocked by omega-agatoxin TK, a P/Q type
      Ca(2+) channel blocker. These data indicate that N/OFQ reduces evoked EPSC, in
      part, by inhibiting the activity of N- and P/Q-type Ca(2+) channels. In addition,
      N/OFQ produced a consistent reduction in baseline Ca(2+) levels in presynaptic
      retinohypothalamic tract terminals. N/OFQ also inhibited evoked GABA(A) receptor
      mediated inhibitory postsynaptic currents (IPSC) in a concentration dependent
      manner. However, N/OFQ had no effect on currents activated by muscimol
      application or on the amplitude of miniature IPSC (mIPSC) and significantly
      reduced the mIPSC frequency consistent with an inhibition of GABA release
      downstream from Ca(2+) entry. Finally, N/OFQ inhibited the paired-pulse
      depression observed in SCN GABAergic synapses consistent with a presynaptic
      mechanism of action. Together these results suggest a widespread modulatory role
      for N/OFQ on the synaptic transmission in the SCN.

PMID- 15857703
TI  - Effects of low dose N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine administration
      on exploratory and amphetamine-induced behavior and dopamine D2 receptor function
      in rats with high or low exploratory activity.
AB  - Individual differences in behavioral traits are associated with sensitivity to
      various neurochemical and psychopharmacological manipulations. In this study
      exploratory and amphetamine-induced behavior in rats with persistently high or
      low exploratory activity (HE and LE, respectively) was examined before and after
      a partial denervation of the locus coeruleus (LC) projections with the selective
      neurotoxin DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine; 10 mg/kg).
      Partial LC denervation prevented the increase in exploratory activity over
      repeated test sessions in the LE animals, but had no effect in HE-rats.
      Amphetamine- (0.5 mg/kg) induced locomotor activity was attenuated by DSP-4
      pretreatment only in HE-rats. These results suggest differential involvement of
      LC noradrenergic transmission in novelty- and amphetamine-induced behavior in
      animals with persistent differences in novelty-related behavior. In addition to
      partial noradrenaline depletion in the frontal cortex and hippocampus, which
      occurred in both HE- and LE-rats, DSP-4 treatment also decreased the content of
      dopamine and its metabolites in the nucleus accumbens, and the metabolite levels
      in striatum, but only in the LE-animals. 5-HIAA levels were also reduced in the
      nucleus accumbens and striatum in LE-rats by the neurotoxin. D(2) receptor
      function, as determined by dopamine-stimulated [(35)S]GTPgammaS binding, was
      increased by DSP-4 treatment in the striatum of LE-rats, but reduced in HE-rats.
      No effect of partial LC denervation was found on dopamine-stimulated
      [(35)S]GTPgammaS binding in the nucleus accumbens. Together these findings
      suggest that LC noradrenergic neurotransmission is differently involved in
      dopaminergic mechanisms which mediate novelty-related vs amphetamine-induced
      behavior.

PMID- 15857704
TI  - Imidazoline receptors associated with noradrenergic terminals in the rostral
      ventrolateral medulla mediate the hypotensive responses of moxonidine but not
      clonidine.
AB  - We determined whether the cardiovascular actions of central anti-hypertensive
      agents clonidine and moxonidine are dependent on noradrenergic or serotonergic
      innervation of the rostral ventrolateral medulla (RVLM) in conscious rabbits. 6
      Hydroxydopamine (6-OHDA) or 5,6-dihydroxytriptamine (5,6-DHT) was injected into
      the RVLM to deplete noradrenergic and serotonergic terminals respectively. One, 2
      and 4 weeks later, responses to fourth ventricular (4V) clonidine (0.65
      microg/kg) and moxonidine (0.44 microg/kg) were examined. Destruction of
      noradrenergic pathways in the RVLM by 6-OHDA reduced the hypotensive response to
      4V moxonidine to 62%, 47% and 60% of that observed in vehicle treated rabbits at
      weeks 1, 2 and 4 respectively. The moxonidine induced bradycardia was similarly
      attenuated (to 46% of vehicle). Conversely, 6-OHDA had no effect on the
      hypotensive or bradycardic effects of 4V clonidine. Efaroxan (I(1)-imidazoline
      receptor/alpha(2)-adrenoceptor antagonist; 3.5, 11, 35 microg/kg) and 2
      methoxyidazoxan (alpha(2)-adrenoceptor antagonist; 0.3, 0.9, 3 microg/kg) equally
      reversed the hypotension to 4V clonidine, suggesting a mainly alpha(2)
      adrenoceptor mechanism. Efaroxan preferentially reversed responses to moxonidine
      in both vehicle and 5,6-DHT groups and in the 1st week after 6-OHDA, suggesting a
      mechanism involving mainly I(1)-imidazoline receptors. This selectivity was
      subsequently lost in the 2nd and 4th weeks when the remaining hypotension was
      mainly mediated by alpha(2)-adrenoceptors. Depletion of serotonergic terminals
      did not alter the responses to either agonist nor did it change the relative
      effectiveness of the antagonists. Western blots of RVLM tissues probed with
      imidazoline and alpha(2)-adrenoceptor antisera showed a pattern of bands close to
      that reported in other species. The main effect of 6-OHDA was an 18% lower level
      of the 42 kDa imidazoline protein (P<0.05). We conclude that the hypotensive and
      bradycardic actions of moxonidine but not clonidine are mediated through
      imidazoline receptors and are dependent on intact noradrenergic pathways within
      the RVLM. Furthermore, the noradrenergic innervation may be associated with a 42
      kDa imidazoline receptor protein.

PMID- 15857705
TI  - Cardiovascular responses to microinjection of nociceptin and endomorphin-1 into
      the nucleus tractus solitarii in conscious rats.
AB  - Increasing evidence suggests an active participation of nociceptinergic
      transmission in the central control of cardiovascular activity and reflex. In
      this study, the role of the classic opioid mu receptor and the
      nociceptin/orphanin FQ receptor, a novel opioid receptor, in the nucleus tractus
      solitarii (NTS) in the regulation of cardiovascular activity was investigated and
      compared in chronically cannulated and freely moving conscious rats.
      Microinjections of nociceptin, an endogenous ligand for the nociceptin receptor,
      into the relatively rostral NTS produced dose-related (0.04, 0.2, and 1 nmol)
      increases in blood pressure and heart rate. Intra-NTS injection of the selective
      nociceptin receptor antagonist [Nphe(1)]Nociceptin(1-13)NH(2) (NOR-AN) at 1 nmol
      blocked the increases in blood pressure and heart rate induced by nociceptin. In
      contrast, pretreatment with the nonselective opioid receptor antagonist naloxone
      (5 nmol) had no effects on the cardiovascular responses to nociceptin. Like
      nociceptin, microinjection of endomorphin-1 (EM-1), an endogenous ligand for the
      opioid mu receptor, into the rostral NTS increased blood pressure and heart rate
      in a dose-dependent manner (0.04, 0.2, and 1 nmol). Pretreatment with naloxone (5
      nmol), but not NOR-AN, blocked cardiovascular responses elicited by EM-1. Neither
      NOR-AN nor naloxone alone had significant effects on the baseline blood pressure
      and heart rate. Injection of excitatory amino acid l-glutamate (1 nmol) into the
      same sites caused the typical depressor and bradycardic responses. In the caudal
      NTS areas, nociceptin and EM-1 seemed to induce opposite responses: hypotension
      and bradycardia. These results suggest that the novel nociceptin receptors and
      traditional opioid receptors in the NTS may be independently involved in the
      regulation of cardiovascular activity.

PMID- 15857706
TI  - Supraspinal and spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid
      and N-methyl-D-aspartate glutamatergic control of the micturition reflex in the
      urethane-anesthetized rat.
AB  - Effects of i.c.v. and i.t. administration of (3SR,4aRS,6RS,8aRS)-6-[2-(1H
      tetrazol-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid (LY215490), a
      competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)
      receptor antagonist and MK-801, a non-competitive N-methyl-D-aspartate (NMDA)
      receptor antagonist on the micturition reflex were evaluated in urethane
      anesthetized rats, to determine if glutamatergic mechanisms in brain as well as
      spinal cord are important for the control of micturition. I.c.v. or i.t.
      injection of LY215490 in low doses (0.01-0.03 microg) did not change rhythmic
      bladder or external urethral sphincter (EUS) electromyogram (EMG) activity during
      continuous cystometrograms (CMGs; 0.21 ml/min), whereas higher doses (0.1-1
      microg) markedly suppressed these responses. During single CMGs (0.04 ml/min),
      0.1-1 microg i.c.v. or 0.1-10 microg i.t. doses increased volume threshold and
      pressure threshold for inducing micturition, and decreased bladder contraction
      amplitude and voiding efficiency. MK-801 in low doses (0.6 microg i.c.v. or 0.6
      1.8 microg for i.t.) did not change bladder contraction amplitude or EUS EMG
      activity during continuous CMGs, whereas higher doses 6-60 microg markedly
      suppressed these responses. During single CMGs, MK-801 (6-60 microg i.c.v. or 60
      microg i.t.) increased volume threshold and pressure threshold, and decreased
      voiding efficiency and bladder contraction amplitude. Pretreatment i.c.v. with MK
      801 in a dose 1.8 microg which alone had little effect on bladder contraction
      amplitude and EUS EMG activity, markedly enhanced depressant effects of LY215490
      (0.03 microg i.c.v.) on these responses. Administration of same doses of drugs by
      i.t. route did not elicit a similar synergistic interaction. These data indicate
      that in urethane-anesthetized rats glutamatergic mechanisms in brain and spinal
      cord are essential for controlling micturition and that interactions between AMPA
      and NMDA glutamatergic transmission are important at supraspinal but not spinal
      sites.

PMID- 15857707
TI  - Dopaminergic-adrenergic interactions in the wake promoting mechanism of
      modafinil.
AB  - Adrenergic signaling regulates the timing of sleep states and sleep state
      dependent changes in muscle tone. Recent studies indicate a possible role for
      noradrenergic transmission in the wake-promoting action of modafinil, a widely
      used agent for the treatment of excessive sleepiness. We now report that
      noradrenergic projections from the locus coeruleus to the forebrain are not
      necessary for the wake-promoting action of modafinil. The efficacy of modafinil
      was maintained after treatment of C57BL/6 mice with N-(2-chloroethyl)-N-ethyl 2
      bromobenzylamine (DSP-4), which eliminates all noradrenaline transporter-bearing
      forebrain noradrenergic projections. However, the necessity for adrenergic
      receptors in the wake-promoting action of modafinil was demonstrated by the
      observation that the adrenergic antagonist terazosin suppressed the response to
      modafinil in DSP-4 treated mice. The wake-promoting efficacy of modafinil was
      also blunted by the dopamine autoreceptor agonist quinpirole. These findings
      implicate non-noradrenergic, dopamine-dependent adrenergic signaling in the wake
      promoting mechanism of modafinil. The anatomical specificity of these
      dopaminergic-adrenergic interactions, which are present in forebrain areas that
      regulate sleep timing but not in brain stem areas that regulate sleep state
      dependent changes in muscle tone, may explain why modafinil effectively treats
      excessive daytime sleepiness in narcolepsy but fails to prevent the loss of
      muscle tone that occurs in narcoleptic patients during cataplexy.

PMID- 15857708
TI  - Food restriction increases NMDA receptor-mediated calcium-calmodulin kinase II
      and NMDA receptor/extracellular signal-regulated kinase 1/2-mediated cyclic amp
      response element-binding protein phosphorylation in nucleus accumbens upon D-1
      dopamine receptor stimulation in rats.
AB  - Biological drive states exert homeostatic control in part by increasing the
      reinforcing effects of environmental incentive stimuli. An apparent by-product of
      this adaptive response is the enhanced acquisition of drug self-administration
      behavior in food-restricted (FR) animals. While previous research has
      demonstrated increased central sensitivity to rewarding effects of abused drugs
      and direct dopamine (DA) receptor agonists in FR subjects, the underlying
      neurobiology is not well understood. Recently, it was demonstrated that
      intracerebroventricular (i.c.v.) injection of the D-1 DA receptor agonist, SKF
      82958 produces a stronger activation of striatal extracellular signal-regulated
      kinase (ERK) 1/2 and cyclic AMP response element-binding protein (CREB) in FR
      relative to ad libitum (AL) fed rats. The main purpose of the present study was
      to characterize the involvement and mechanisms of interaction between NMDA
      receptor function and the augmented cellular responses to D-1 DA receptor
      stimulation in nucleus accumbens (NAc) of FR rats. In experiment 1, Western
      immunoblotting was used to demonstrate that i.c.v. injection of SKF-82958 (20
      microg) produces greater phosphorylation of the NMDA NR1 subunit and calcium
      calmodulin kinase II (CaMK II) in NAc of FR as compared with AL rats. In
      experiment 2, pretreatment of subjects with the NMDA antagonist, MK-801 (1.0
      mg/kg, i.p.) decreased SKF-82958-induced activation of CaMK II, ERK1/2 and CREB,
      and reversed the augmenting effect of FR on activation of all three proteins. In
      experiment 3, pretreatment with the mitogen-activated protein kinase/ERK kinase
      inhibitor SL-327 (60 mg/kg, i.p.) suppressed SKF-82958- induced activation of
      ERK1/2 and reversed the augmenting effect of FR on CREB activation. These results
      point to specific neuroadaptations in the NAc of FR rats whereby D-1 DA receptor
      stimulation leads to increased NMDA NR1 subunit phosphorylation and consequent
      increases in NMDA receptor-dependent CaMK II and ERK1/2 signaling, and increased
      NMDA receptor/ERK1/2-dependent phosphorylation of the nuclear transcription
      factor, CREB. The upregulated cellular responses to D-1 DA agonist challenge may
      play a role in the augmentation of drug reward and appetitive instrumental
      learning during periods of food restriction.

PMID- 15857709
TI  - Potentiation, activation and blockade of GABAA receptors by etomidate in the rat
      sacral dorsal commissural neurons.
AB  - Etomidate (ET), an imidazole general anesthetic, has been medically widely used.
      Recent evidence suggests that the inhibitory neurotransmitter GABA receptor may
      be one of the important molecular target(s) of general anesthetics. Up to date,
      little attention has been directed toward the sacral dorsal commissural nucleus
      (SDCN), which serves as a relay of sensory information from the pelvic viscera in
      the spinal cord. Therefore, the effect of ET on GABA(A) receptor function in
      neurons acutely dissociated from the SDCN was investigated using the nystatin
      perforated patch-recording configuration under voltage-clamp conditions. At a
      holding potential of -40 mV, ET (above 10 microM) induced an inward ET-activated
      current (I(ET)) with the EC(50) value of 33 +/- 3 microM, which was reversibly
      blocked by bicuculline and picrotoxin. The reversal potential of I(ET) was close
      to the Cl(-) equilibrium potential. ET also displayed a biphasic modulatory
      effect on GABA responses. At lower concentrations (0.1-100 microM), ET reversibly
      potentiated GABA (1 microM)-activated Cl(-) currents in a bell-shaped manner,
      with the maximal facilitative effect at 10 microM, whereas at concentrations >100
      microM, the peak of the ET-induced current was suppressed in the absence or
      presence of GABA (1 microM). These results suggest that in SDCN, in addition to
      the potentiation of GABA(A) receptor-mediated responses at low concentrations and
      the direct activation of GABA(A) receptors at moderate concentrations as
      expected, ET produced a fast blocking action at high concentrations. The general
      anesthetic-induced effects in SDCN, at least the potentiation of GABA responses,
      may significantly contribute to anesthesia of pelvic viscera during the general
      anesthesia.

PMID- 15857710
TI  - Monoaminergic dysregulation in glutathione-deficient mice: possible relevance to
      schizophrenia?
AB  - Several lines of research have implicated glutathione (GSH) in schizophrenia. For
      instance, GSH deficiency has been reported in the prefrontal cortex of
      schizophrenics in vivo. Further, in rats postnatal GSH-deficiency combined with
      hyperdopaminergia led to cognitive impairments in the adult. In the present
      report we studied the effects of 2-day GSH-deficiency with L-buthionine-(S,R)
      sulfoximine on monoaminergic function in mice. The effect of GSH-deficiency per
      se and when combined with the amphetamine and phencyclidine (PCP) models of
      schizophrenia was investigated. GSH-deficiency significantly altered tissue
      levels of dopamine (DA), 5-hydroxytryptamine (5-HT) and their respective
      metabolites homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in a
      region-specific fashion. The effects of GSH-deficiency on tissue monoamines were
      distinct from and, generally, did not interact with the effects of amphetamine (5
      mg/kg; i.p.) on tissue monoamines. Microdialysis studies showed that
      extracellular DA-release after amphetamine (5 mg/kg, i.p.) was two-fold increased
      in the nucleus accumbens of GSH-deficient mice as compared with control mice.
      Basal DA was unaltered. Further, extracellular levels of HVA in the frontal
      cortex and hippocampus and 5-HIAA in the nucleus accumbens were elevated by GSH
      deficiency per se. Spontaneous locomotor activity in the open field was unchanged
      in GSH-deficient mice. In contrast, GSH-deficiency modulated the locomotor
      responses to mid-range doses of amphetamine (1.5 and 5 mg/kg, i.p.). Further, GSH
      deficient mice displayed an increased locomotor response to low (2 and 3 mg/kg,
      i.p.) doses of phencyclidine (PCP). In conclusion, the data presented here show
      that even short-term GSH-deficiency has consequences for DA and 5-HT function.
      This was confirmed on both neurochemical and behavioral levels. How GSH and the
      monoamines interact needs further scrutiny. Moreover, the open field findings
      suggest reduced or altered N-methyl-d-aspartate (NMDA) receptor function in GSH
      deficient mice. Thus, GSH-deficiency can lead to disturbances in DA, 5-HT and
      NMDA function, a finding that may have relevance for schizophrenia.

PMID- 15857711
TI  - The contribution of peripheral 5-hydroxytryptamine2A receptor to carrageenan
      evoked hyperalgesia, inflammation and spinal Fos protein expression in the rat.
AB  - The present study was conducted to test the hypothesis that the peripheral 5
      hydroxytryptamine (5-HT)2A receptor is involved in inflammatory hyperalgesia and
      production of noxious stimulus-induced neuronal activity at the level of the
      spinal cord dorsal horn. Intraplantar (i.pl.) injection of carrageenan
      dramatically reduced paw withdrawal latency to noxious heat (47 degrees C) and
      caused paw swelling. Pretreatment with ketanserin, a selective antagonist of 5
      HT2A receptor, in the hindpaw produced dose-dependent inhibition of the
      hyperalgesia (0.5, 3 and 5 mug; i.pl.) with full relief at 5 mug. The drug also
      moderately reduced carrageenan-induced paw swelling in a dose-dependent manner.
      Carrageenan induced conspicuous expression of c-fos-like immunoreactivity (FLI)
      in the spinal dorsal horn of segments L4-5. Ketanserin (5 mug) markedly reduced
      carrageenan-induced FLI in all laminae of the dorsal horn. However, blockade of
      peripheral 5-HT1A receptors by (N-2-[4-(2-methoxyphenyl-1-piperazinyl] ethyl]-N-2
      pyridinylcyclohexanecarboxamide at maximally effective doses (30 and 100 mug;
      i.pl.) did not alter carrageenan-induced hyperalgesia, edema or expression of
      FLI. The present study provided evidence at cellular level that the peripheral 5
      HT2A receptor is preferentially involved in the development of thermal
      hyperalgesia in the carrageenan model of inflammation.

PMID- 15857712
TI  - Differential effect of p75 neurotrophin receptor on expression of pro-apoptotic
      proteins c-jun, p38 and caspase-3 in dorsal root ganglion cells after axotomy in
      experimental diabetes.
AB  - We have hypothesized that p75 neurotrophin receptor (p75(NTR))-mediated
      activation of the pro-apoptotic proteins c-jun, p38 and caspase-3 underlies the
      neuronal cell loss in dorsal root ganglia (DRG) neurons after axotomy in normal
      mice, and that this activation is exaggerated in experimental diabetes. To test
      this hypothesized relationship, we compared the expression of pro-apoptotic
      proteins in fifth lumbar DRG (L5DRG) neurons of wildtype Balb/c (p75+/+) mice and
      p75(NTR) knockout (p75-/-) mice, assigned to either non-diabetic control groups
      or to diabetic (1 month) groups, all with a unilateral sciatic nerve crush
      produced 10 days before tissue preparation. The absolute number of L5DRG neurons
      expressing immunoreactivities (IR) for phosphorylated c-jun (P-c-jun-IR),
      phosphorylated p-38 (P-p38-IR) and cleaved caspase-3 (caspase-3-IR) were
      estimated in semi-thick sections using the optical fractionator. Nerve crush
      increased the numbers of P-c-jun-IR and caspase-3-IR neurons in all four groups.
      On the crush side, diabetes did not exaggerate the increase of P-c-jun-IR or
      caspase-3-IR neurons in p75+/+ mice, whereas in p75-/- mice diabetes reduced the
      increase of P-c-jun-IR neurons. Also, in p75-/- mice there was fewer caspase-3-IR
      cells on the intact and crushed side in comparison with p75+/+ mice independent
      of the presence of diabetes. This study demonstrates that (1) diabetes of 1
      month's duration does not potentiate the expression of three pro-apoptotic
      markers p38, caspase-3 and P-c-jun neither in intact neurons nor after nerve
      crush, and that (2) p75(NTR) is required for activation of the pro-apoptosis
      signal caspase-3 after nerve crush in both diabetic and non-diabetic mice.

PMID- 15857713
TI  - Behavioral, pharmacological and molecular characterization of the saphenous nerve
      partial ligation: a new model of neuropathic pain.
AB  - The saphenous partial ligation (SPL) model is a new, easily performed, rodent
      model of neuropathic pain that consists of a unilateral partial injury to the
      saphenous nerve. The present study describes behavioral, pharmacological and
      molecular properties of this model. Starting between 3 and 5 days after surgery,
      depending on the modality tested, animals developed clear behaviors indicative of
      neuropathic pain such as cold and mechanical allodynia, and thermal and
      mechanical hyperalgesia compared with naive and sham animals. These pain
      behaviors were still present at 1 month. Signs of allodynia also extended to the
      sciatic nerve territory. No evidence of autotomy or bodyweight loss was observed.
      Cold and mechanical allodynia but not thermal and mechanical hyperalgesia was
      reversed by morphine (4 mg/kg i.p.). The cannabinoid receptor agonist WIN 55,212
      2 (5 mg/kg i.p.) improved signs of allodynia and hyperalgesia tested except for
      mechanical hyperalgesia. Gabapentin (50 mg/kg i.p.) was effective against cold
      and mechanical allodynia but not hyperalgesia. Finally, amitriptyline (10 mg/kg
      i.p.) failed to reverse allodynia and hyperalgesia and its administration even
      led to hyperesthesia. Neurobiological studies looking at the expression of mu
      opioid receptor (MOR), cannabinoid CB(1) and CB(2) receptors showed a significant
      increase for all three receptors in ipsilateral paw skin, L3-L4 dorsal root
      ganglia and spinal cord of neuropathic rats compared with naive and sham animals.
      These changes in MOR, CB(1) and CB(2) receptor expression are compatible with
      what is observed in other neuropathic pain models and may explain the analgesia
      produced by morphine and WIN 55,212-2 administrations. In conclusion, we have
      shown that the SPL is an adequate model that will provide a new tool for
      clarifying peripheral mechanisms of neuropathic pain in an exclusive sensory
      nerve.

PMID- 15857714
TI  - Age-related loss of the GABA synthetic enzyme glutamic acid decarboxylase in rat
      primary auditory cortex.
AB  - Age-related changes within the auditory brainstem typically include alterations
      in inhibitory neurotransmission and coding mediated by GABA and glycinergic
      circuits. As part of an effort to evaluate the impact of aging on
      neurotransmission in the higher auditory centers, the present study examined age
      related changes in the GABA synthetic enzyme, glutamic acid decarboxylase (GAD),
      in rat primary auditory cortex (AI), which contains a vast network of intrinsic
      and extrinsic GABAergic circuits throughout its layers. Message levels of the two
      GAD isoforms found in brain, GAD(65) and GAD(67), and GAD(67) protein levels were
      compared in young adult, middle-aged and aged rats using in situ hybridization
      and quantitative immunocytochemistry, respectively. For comparison, age-related
      GAD changes were also assessed in the parietal cortex and hippocampus.
      Significant age-related decreases in GAD(65&67) messages were observed in AI
      layers II-VI of aged rats relative to their young adult cohorts. The largest
      changes were identified in layer II (GAD(65): -26.6% and GAD(67): -40.1%).
      GAD(67) protein expression decreased significantly in parallel with mRNA
      decreases in all layers of AI. Adjacent regions of parietal cortex showed no
      significant GAD(67) protein changes among the age groups, except in layer IV. As
      previously described, GAD(67) message and protein levels in selected hippocampal
      regions were significantly reduced in aged rats. Age-related GAD reductions
      likely reflect decreases in both metabolic and pre-synaptic GABA levels
      suggesting a plastic down-regulation of normal adult inhibitory GABA
      neurotransmission. Consistent with the present findings, functional studies in
      primate visual cortex and preliminary studies in AI find coding changes
      suggestive of altered inhibitory processing in aged animals. An age-related loss
      of normal adult GABA neurotransmission in AI would likely alter temporal coding
      properties and could contribute to the loss in speech understanding observed in
      the elderly.

PMID- 15857715
TI  - Identification of chicken transmembrane channel-like (TMC) genes: expression
      analysis in the cochlea.
AB  - Mutations of the human gene encoding transmembrane channel-like protein (TMC)1
      cause dominant and recessive nonsyndromic hearing disorders, suggesting that this
      protein plays an important role in the inner ear. In this study, we cloned
      chicken Tmc2 (GgTmc2) from a cochlear cDNA library and we annotated four
      additional TMC family members: GgTmc1, GgTmc3, GgTmc6, and GgTmc7. All chicken
      TMCs possess the defining TMC signature motif and display high conservation of
      their genomic structure when compared with other vertebrate TMC genes. GgTmc1 is
      localized on the chicken sex chromosome Z at a locus that displays conserved
      synteny with the loci of mammalian orthologues residing on autosomes. In
      contrast, the locus of GgTmc2 does not exhibit conserved synteny with its
      mammalian orthologues. Because murine TMC1 and TMC2 are restrictively expressed
      in cochlear hair cells, we determined the expression of the chicken orthologues
      in the basilar papilla, the avian equivalent of the organ of Corti. While GgTmc2
      was present throughout the basilar papilla and in other tissues, GgTmc1
      transcript was detected specifically in the basal portion of the basilar papilla
      and was not detectable in any other tissue or organ studied. GgTmc3 and GgTmc6
      were detectable in all organs analyzed. Antibody labeling revealed that GgTmc2 is
      predominantly associated with the lateral membranes of hair and supporting cells.
      The expression of GgTmc2 by both cell types was further confirmed by RT-PCR using
      isolated cells. This expression and subcellular localization of GgTmc2 is in
      agreement with the proposed potential role of this novel class of transmembrane
      proteins in ion transport.

PMID- 15857716
TI  - Discharge patterns of somatosensitive neurons in the nucleus tractus solitarius
      of the cat.
AB  - Encoding of sensory information by nucleus of the solitary tract (NTS) neurons is
      incompletely understood. Using extracellular single-unit recording in alpha
      chloralose-urethane anesthetized cats, we have examined the discharge
      characteristics of NTS neurons to activation of somatic Adelta and C fiber
      afferents by skeletal muscle contraction evoked by electrical stimulation of
      lower lumbar/upper sacral ventral roots. Generally, somatic afferent stimulation
      evoked two distinct firing patterns. The first population (36/43 cells) increased
      their firing rate to brief somatic stimuli. A subset (21/27 cells) exhibited a
      rapid decay of their firing rate during sustained somatic stimulation. Peak
      instantaneous firing frequency (F(p)) increased proportionally with the intensity
      of somatic stimulation (105+/-4 vs. 119+/-4 vs. 139+/-4 Hz, 10, 20 and 40 Hz,
      respectively, P<0.0001), whereas steady-state firing frequency (F(ss)) was not
      altered (25+/-2 vs. 27+/-2 vs. 27+/-2 Hz, 10, 20 and 40 Hz, respectively,
      P=0.72). Two indices were derived to quantify the decay properties. The decay
      rate constant (obtained from exponential curve fitting) was not altered by
      stimulation frequency (461+/-10 vs. 442+/-14 vs. 429+/-26 ms, 10, 20 and 40 Hz,
      respectively, P=0.415), nor was the decay index (derived to express the percent
      reduction in firing rate with respect to the initial peak firing rate; 76+/-2 vs.
      77+/-2 vs. 81+/-2%, 10, 20 and 40 Hz, respectively, P=0.187). In contrast, the
      second population (seven of 43 cells) decreased their firing rate to stimulation.
      Of the NTS neurons tested for barosensitivity (29/36), none responded to pressure
      stimulation. These results have identified a population of somatosensitive NTS
      neurons that exhibit rapid firing rate decay properties during sustained
      stimulation. However, this population could faithfully encode phasic excitation
      during rhythmic somatosensory input. These results are discussed in relation to
      the role of somatosensory input on baroreflex function.

PMID- 15857717
TI  - Age-dependent reduction of gamma oscillations in the mouse hippocampus in vitro.
AB  - Normal brain ageing is associated with a decline in hippocampal memory functions.
      Neuronal oscillations in the gamma frequency band have been implicated in various
      cognitive tasks. In this study we test the effect of normal brain ageing on gamma
      oscillations in the mouse hippocampus in vitro. gamma Oscillations were evoked by
      either 10 microM carbachol or 100 nM kainate in ventral hippocampus slices from
      young (>5 month) and aged (>22 month) C57Bl/J6 mice. In slices from young mice
      carbachol-induced gamma oscillations were more regular and more coherent than
      those induced by kainate. Compared with young, the power in the 20-80 Hz
      frequency range in area CA3 of slices from aged mice was reduced to 14% for
      kainate-induced oscillations and to 7% for carbachol-induced oscillations,
      whereas waveform, dominant frequency and coherence of the oscillation were
      unchanged. Local network properties were assessed by paired-pulse stimulation of
      Schaffer collateral/commissural fibers. The excitatory synaptic response in
      stratum radiatum of CA3 was reduced, in correlation with the antidromic
      population spike, but functional inhibition in CA3 and CA1 was unaffected.
      Changes in local network properties could not explain the reduced gamma
      oscillation strength. Since oscillations driven by two different pathways are
      similarly affected with age, an age-dependent effect on tonic depolarizing drive
      of principal cells is unlikely to explain the current results. Other mechanisms,
      including a change with age in the use-dependent modulation of synaptic strength,
      should account for the impaired gamma oscillations in the aged hippocampus that
      may contribute to age-dependent memory impairment.

PMID- 15857718
TI  - Blunted response to cocaine in the Flinders hypercholinergic animal model of
      depression.
AB  - The Flinders sensitive line (FSL) rat is a proposed genetic hypercholinergic
      animal model of human depression. Considering the strong comorbidity between
      depression and cocaine dependence we investigated the well-documented behavioral
      and molecular effects of cocaine in the FSL and their control Flinders resistant
      line (FRL) rats. First, we found no difference between the two lines to establish
      cocaine self-administration; both lines reached stable responding within 10 days
      of training at a fixed ratio-1 schedule of reinforcement (1.5 mg/kg/injection).
      However, the FSL rats exhibited reduced cocaine intake at a dose of 0.09
      mg/kg/injection in a within-session dose-response curve (0.02, 0.09, 0.38, 1.5
      mg/kg/injection). Second, we examined the effects of repeated cocaine
      administration on locomotor activity, dopamine overflow and striatal prodynorphin
      mRNA expression. We found the FSL rats to be low responders to novelty and to
      exhibit less locomotor activation after repeated cocaine administration (30
      mg/kg, i.p., daily injections for 10 days) than their controls. Microdialysis
      sampling from the nucleus accumbens shell revealed no significant difference in
      the dopamine overflow between the rat lines, neither during baseline nor after
      cocaine stimulation. Postmortem analyses of striatal prodynorphin mRNA expression
      (using in situ hybridization histochemistry) revealed a differentiated response
      to the cocaine exposure. In contrast to control FRL rats, the FSL rats showed no
      typical cocaine-evoked elevation of prodynorphin mRNA levels in rostral
      subregions of the striatum whereas both strains expressed increased prodynorphin
      mRNA levels in the caudal striatum after cocaine administration. In conclusion,
      the FSL animal model of depression demonstrates marked blunting of the locomotor
      and dynorphin neuroadaptative responses to cocaine in accordance with its
      enhanced cholinergic sensitivity.

PMID- 15857719
TI  - Neuronal expression of cAMP-specific phosphodiesterase 7B mRNA in the rat brain.
AB  - cAMP plays an important role as second messenger molecule controlling multiple
      cellular processes in the brain. cAMP levels depend critically on the
      phosphodiesterases (PDE) activity, enzymes responsible for the clearance of
      intracellular cAMP. We have examined the regional distribution and cellular
      localization of mRNA coding for the cAMP-specific phosphodiesterase 7B (PDE7B) in
      rat brain by in situ hybridization histochemistry. PDE7B mRNA is specifically
      distributed in rat brain, preferentially in neuronal cell populations. The
      highest levels of hybridization are observed in olfactory tubercle, islands of
      Calleja, dentate gyrus, caudate-putamen and some thalamic nuclei. Positive
      hybridization signals are also detected in other areas, such as cerebral cortex,
      Purkinje cells of the cerebellum and area postrema. By double in situ
      hybridization histochemistry, we found that 74% and 79% of the cells expressing
      PDE7B mRNA in striatum and olfactory tubercle, respectively, were GABAergic cells
      (expressing glutamic acid decarboxylase mRNA), in contrast with the lack of
      expression in the few cholinergic cells (expressing choline acetyltransferase
      mRNA) present in those two areas (around 0.4% in olfactory tubercle). In the
      thalamic nuclei, a majority of cells containing PDE7B mRNA also expresses a
      glutamatergic marker (76.7% express vesicular glutamate transporter vGluT1 and
      76% express vGluT2 mRNAs). Almost all PDE7B expressing cells in dentate gyrus
      (93%) were glutamatergic. These results offer a neuroanatomical and neurochemical
      base that will support the search for specific functions for cAMP dependent PDEs
      and for the development of specific PDE7 inhibitors.

PMID- 15857720
TI  - Characteristics of the electrical oscillations evoked by 4-aminopyridine on
      dorsal root fibers and their relation to fictive locomotor patterns in the rat
      spinal cord in vitro.
AB  - 4-Aminopyridine (4-AP) is suggested to improve symptomatology of spinal injury
      patients because it may facilitate neuromuscular transmission, spinal impulse
      flow and the operation of the locomotor central pattern generator (CPG). Since 4
      AP can also induce repetitive discharges from dorsal root afferents, this
      phenomenon might interfere with sensory signals necessary to modulate CPG
      activity. Using electrophysiological recording from dorsal and ventral roots of
      the rat isolated spinal cord, we investigated 4-AP-evoked discharges and their
      relation with fictive locomotor patterns. On dorsal roots 4-AP (5-10 microM)
      induced sustained synchronous oscillations (3.3+/-0.8 s period) smaller than
      electrically evoked synaptic potentials, persistent after sectioning off the
      ventral region and preserved in an isolated dorsal quadrant, indicating their
      dorsal horn origin. 4-AP oscillations were blocked by tetrodotoxin, or 6-cyano-7
      nitroquinoxaline-2,3-dione and d-amino-phosphonovalerate, or strychnine and
      bicuculline, suggesting they were network mediated via glutamatergic, glycinergic
      and GABAergic transmission. Isolated ventral horn areas could not generated 4-AP
      oscillations, although their intrinsic disinhibited bursting was accelerated by 4
      AP. Thus, ventral horn areas contained 4-AP sensitive sites, yet lacked the
      network for 4-AP induced oscillations. Activation of fictive locomotion by either
      application of N-methyl-D-aspartate and serotonin or stimulus trains to a single
      dorsal root reversibly suppressed dorsal root oscillations induced by 4-AP. This
      suppression was due to depression of dorsal network activity rather than simple
      block of root discharges. Since dorsal root oscillations evoked by 4-AP were
      turned off when the fictive locomotor program was initiated, these discharges are
      unlikely to interfere with proprioceptive signals during locomotor training in
      spinal patients.

PMID- 15857721
TI  - Substance use disorder patients who are mandated to treatment: characteristics,
      treatment process, and 1- and 5-year outcomes.
AB  - A substantial number of patients with substance use disorders (SUDs) are mandated
      to treatment by the justice system. However, little is known about their
      characteristics and how they fare during treatment and in the longer term
      compared with nonmandated, justice-system-involved patients and patients not
      involved in the justice system. This prospective study (n=2,095) examined
      differences in pretreatment characteristics, treatment perceptions and
      satisfaction, during-treatment changes, and 1- and 5-year outcomes among these
      three types of patients and tested whether differences in pretreatment
      characteristics or during-treatment changes could help explain posttreatment
      outcome similarities or differences. Mandated patients had a less severe clinical
      profile at treatment intake, yet this did not account for their observed
      similar/better outcomes, which appeared because of the similar therapeutic gains
      made during treatment. Treatment perceptions and satisfaction were also
      comparable across groups. These findings appear to support the idea that judicial
      mandates can provide an opportunity for offenders with SUDs to access and benefit
      from needed treatment.

PMID- 15857722
TI  - Illicit use of opioid analgesics by high school seniors.
AB  - The illicit use of opioid analgesics represents a growing problem among American
      adolescents. In order to examine the correlates associated with the illicit use
      of opioid analgesics, a nationally representative sample of 4,522 high school
      seniors from the 2002 Monitoring the Future database was examined. Multivariate
      logistic regression indicated that illicit users of prescription opioid
      analgesics were significantly more likely to be male, White, and have lower grade
      point averages. Illicit users of opioid analgesics also reported higher rates of
      cigarette smoking, alcohol use, marijuana use, other illicit drug use, and
      problem behaviors. The present study provides evidence that the illicit use of
      opioid analgesics represents a problem among American high school seniors and
      effective prevention and intervention efforts are needed.

PMID- 15857723
TI  - When treatment meets research: clinical perspectives from the CSAT
      Methamphetamine Treatment Project.
AB  - Integrating research-based treatments into clinical settings has become a
      priority in the substance abuse treatment field. This article examines the
      introduction of research, via manualized treatment (i.e., the Matrix Model), into
      community treatment settings that participated in the Center for Substance Abuse
      Treatment Methamphetamine Treatment Project, a multi-site randomized controlled
      trial (RCT) that provided free treatment to 1016 methamphetamine-dependent
      individuals. With both empirical (qualitative) and anecdotal data from those
      involved clinically in the project, the article utilizes the framework of
      practitioner concerns set forth by Addis, Wade, and Hatgis (1999) to assess the
      issues realized during the implementation of this manualized treatment. Despite
      fairly smooth implementation of the model, the authors conclude that introducing
      manualized treatment in the context of an RCT may not be the best way to bring
      research-based treatment into the practice world.

PMID- 15857724
TI  - Training substance abuse treatment staff to care for co-occurring disorders.
AB  - Although co-occurring disorders have been associated with poorer substance abuse
      treatment outcomes and higher costs of care, few individuals with co-occurring
      disorders receive appropriate mental health care. This article describes the
      design and implementation of an intervention to improve the quality of mental
      health care provided in outpatient substance abuse treatment programs without
      requiring new treatment staff. The intervention focuses on individuals with
      affective and anxiety disorders and consists of three components: training and
      supervising staff, educating and activating clients, and linking with community
      resources. We evaluated three treatment programs (one intervention and two
      comparison) for the first component by having program staff complete both self
      administered questionnaires and semistructured interviews. Staff knowledge and
      attitudes about co-occurring disorders, job satisfaction, and morale all
      indicated an improvement at the intervention relative to the comparison sites.
      The evaluation is still under way; results for implementation of the other two
      components and for outcomes will be reported later.

PMID- 15857726
TI  - Factors associated with 12 months continuous heroin abstinence: findings from the
      Australian Treatment Outcome Study (ATOS).
AB  - AIMS: To determine the role of treatment and client characteristics associated
      with the achievement of continuous heroin abstinence. DESIGN: Longitudinal cohort
      study. SETTING: Sydney and Adelaide, Australia. PARTICIPANTS: 570 heroin users re
      interviewed at 12 month follow-up for the Australian Treatment Outcome Study
      (ATOS). FINDINGS: Continuous heroin abstinence was reported by 14% of
      participants. Continuous abstinence was associated with no previous treatment
      history, having entered treatment at baseline, and cumulative treatment exposure
      over the follow-up period. Longer retention times in index maintenance and
      residential rehabilitation treatments, but not detoxifications, were most
      associated with abstinence. At baseline, abstinent participants were more likely
      to have been classified as treatment ready, or to have used heroin less
      frequently; and less likely to have been daily injectors, using cocaine or
      criminally involved. CONCLUSIONS: Approximately 14% of ATOS participants achieved
      continuous heroin abstinence over 12 months. Such an achievement was strongly
      associated with a longer "dose" of treatment, and with more treatment stability
      over the follow-up period.

PMID- 15857725
TI  - Influence of psychotherapy attendance on buprenorphine treatment outcome.
AB  - We evaluated the influence of psychotherapy attendance on treatment outcome in 90
      dually (cocaine and heroin) dependent outpatients who completed 70 days of a
      controlled clinical trial of sublingual buprenorphine (16 mg, 8 mg, or 2 mg
      daily, or 16 mg every other day) plus weekly individual standardized
      interpersonal cognitive psychotherapy. Treatment outcome was evaluated by
      quantitative urine benzoylecgonine (BZE) and morphine levels (log-transformed),
      performed three times per week. Repeated-measures linear regression was used to
      assess the effects of psychotherapy attendance (percent of visits kept),
      medication group, and study week on urine drug metabolite levels. Mean
      psychotherapy attendance was 71% of scheduled visits. Higher psychotherapy
      attendance was associated with lower urine BZE levels, and this association grew
      more pronounced as the study progressed (p=0.04). The inverse relationship
      between psychotherapy attendance and urine morphine levels varied by medication
      group, being most pronounced for subjects receiving 16 mg every other day
      (p=0.02). These results suggest that psychotherapy can improve the outcome of
      buprenorphine maintenance treatment for patients with dual (cocaine and opioid)
      dependence.

PMID- 15857727
TI  - Characteristics of older opioid maintenance patients.
AB  - The aging "baby boomer" population has higher rates of substance use than
      previous cohorts and is predicted to put increased demands on substance abuse
      treatment services; however, little is known about older illicit drug abusers.
      This study compared 41 older (age 50-66 years) and 26 younger (age 25-34 years)
      opioid maintenance patients on psychiatric, substance use, medical, general
      health, demographic, and psychosocial characteristics using standardized
      instruments. The health of both groups was compared to age and sex-matched U.S.
      population norms. Both groups had high rates of lifetime psychiatric and
      substance abuse/dependence diagnoses, and poor general health compared to
      population norms. The older group began using illicit substances significantly
      later in life, and had significantly more medical problems and worse general
      health than the younger group. The inevitable increasing medical morbidity and
      physical limitations of an increasingly large older population with substance use
      problems will challenge treatment providers and planners. Low rates of positive
      urine opioid tests occurred for both older and younger patients without age
      specific services.

PMID- 15857728
TI  - Adoption of naltrexone to treat alcohol dependence.
AB  - Three surveys (1997, 1999, and 2001) of outpatient substance abuse treatment
      centers in Connecticut, Massachusetts, Rhode Island, Maine, Vermont, and New
      Hampshire examined organizational characteristics that influenced the adoption of
      naltrexone. Structural equation modeling with manifest variables assessed
      predictors related to the use of naltrexone. Use of naltrexone increased over
      time from 14% in 1997 to 25% in 2001. In 1997, programs funded by managed care
      were more likely, and clinics that provided only substance abuse services were
      less likely to use psychiatric medication and naltrexone. In subsequent years,
      counselor education level and organization size also influenced use of
      naltrexone.

PMID- 15857729
TI  - Developing CASPAR: a computer-assisted system for patient assessment and
      referral.
AB  - A study was completed on the use of a computer-based system that provided
      counselors with resources for client referrals to free or low-cost services
      within the community based on problems identified with an Addiction Severity
      Index (ASI) assessment. That study, completed in Philadelphia, found that in
      comparison with clients whose counselors received a standard ASI assessment
      training, clients whose counselors also received brief training on the simple,
      easy-to-use computer-based resource guide (RG) had treatment plans that were
      substantially better-matched to their presenting problems and received
      significantly more and better-matched services. Because of these favorable
      results, the current article presents further data on counselor use of the RG
      and, to facilitate the implementation of these procedures by others, we provide
      access to the original RG database, describe the steps necessary to develop, and
      maintain an RG, and provide training suggestions.

PMID- 15857730
TI  - Length of outpatient addiction treatment and risk of rehospitalization.
AB  - Several studies, mainly from the U.S. and usually with selected male samples,
      show that aftercare is positively related to lower risk of re-addiction or re
      treatment. The present study extends this line of research in a report from
      public health health care addiction treatment services in Stockholm County. The
      study sample comprises all 196 men and 100 women alcohol-dependent patients from
      10 districts hospitalized for at least 2 days during 1997-99 and who received
      outpatient care within 5 days. These patients were followed up until 2000,
      without attrition for renewed rehospitalization. Greater length of outpatient
      treatment was significantly related to reduced rehospitalization, but only in
      men. The intensity (average number of visits) of outpatient treatment was not
      significantly related to rehospitalization. The different effect of length of
      outpatient treatment between the genders may be due to differences in severity of
      alcohol dependence, social situation, psychiatric co-morbidity, and/or the extent
      to which treatment met patients' needs.

PMID- 15857731
TI  - Opioid-related musical hallucinations.

PMID- 15857732
TI  - Subanesthetic ketamine for cancer pain: by insisting on level I/II evidence, do
      we risk throwing the baby out with the bath water?

PMID- 15857733
TI  - Development of opioid-induced delirium while on olanzapine: a two-case report.

PMID- 15857734
TI  - Quality palliative care: practitioners' needs for dynamic lifelong learning.

PMID- 15857735
TI  - Opioid rotation from methadone: fraught with difficulties.

PMID- 15857736
TI  - Use of opioids in a Danish population-based cohort of cancer patients.
AB  - Until recently, Denmark has had the highest use of strong opioids per capita in
      the world. Our aim was to analyze cancer patients' use of opioids in this
      population by linkage between the Danish Cancer Register and a prescription
      database. The changes in opioid use from 1994 to 1998 in the entire cohort of
      cancer patients (n=24,190) in a Danish county (n approximately 470,000) were
      analyzed. The overall consumption of opioids increased from 20 kg to 37 kg oral
      morphine equivalents (omeq) per year. The average consumption increased from 7.6
      to 10.7 g omeq/opioid user/year. The annual proportion of users increased from
      17% to 20%. The proportion of patients who were alive 2 years after their first
      opioid prescription increased from 38% to 55%. Increased awareness towards pain
      treatment, with earlier initiation of opioid treatment and higher doses to the
      cancer patients, could be major explanations for the increase in the cancer
      patients' use of opioids.

PMID- 15857737
TI  - Fear of death and good death among the young and elderly with terminal cancers in
      Taiwan.
AB  - Fear of death is a common characteristic among palliative care patients. We might
      think that the elderly display a higher degree of acceptance of the inevitability
      and less fear in the face of death. This study was aimed at investigating the
      relationship between the death fear level and the good-death scale in two age
      groups. The study was conducted in 224 patients with terminal cancers admitted to
      the Palliative Care Unit in National Taiwan University Hospital during the period
      of January 1 through October 31, 2001. The mean age was 62.13 +/- 15.47 years.
      The duration of admission in the elderly group was shorter than that of the
      younger group (P < 0.05). The severity of death fear decreased gradually in both
      groups after being admitted to the hospice (P < 0.05). However, the elderly (> or
      = 65 years of age) displayed higher levels of death fear than the younger group
      at two days before death (P < 0.05). A significant negative correlation was
      observed between the degree of death fear and the total good death score in both
      groups at two days before death (P < 0.05). The comprehensive care in the
      palliative care unit might relate to the relief of the death fear of terminal
      cancer patients. There is a need for psychological and spiritual care in elderly
      patients.

PMID- 15857738
TI  - Palliation of bone pain in prostate cancer using chemotherapy and strontium-89. A
      randomized phase II study.
AB  - Strontium-89 is an established alternative for the alleviation of bone pain in
      prostate cancer. There are few data evaluating the effect on pain of palliative
      chemotherapy. The aim of this randomized phase II study was to assess and compare
      the analgesic efficacy of strontium-89 and chemotherapy (FEM=5-FU, epirubicin,
      and mitomycin C) in 35 patients with disseminated, hormone-refractory prostate
      cancer suffering from persisting bone pain despite analgesic treatment. In order
      to minimize the risk for imbalances regarding the two patient groups, a double
      blind randomization was performed. A significant reduction in pain intensity and
      pain frequency was registered in both patient groups (P < 0.01 in both groups
      after 3 weeks). Side effects were generally mild in the strontium-89 group and
      significantly more severe in the FEM group. The effect of FEM on pain is
      surprising as chemotherapy has generally only limited effect on tumor growth in
      bone metastases due to prostate cancer. A possible explanation is that FEM has an
      inhibitory activity on the inflammatory component of metastases.

PMID- 15857739
TI  - Cannabis use in HIV for pain and other medical symptoms.
AB  - Despite the major benefits of antiretroviral therapy on survival during HIV
      infection, there is an increasing need to manage symptoms and side effects during
      long-term drug therapy. Cannabis has been reported anecdotally as being
      beneficial for a number of common symptoms and complications in HIV infections,
      for example, poor appetite and neuropathy. This study aimed to investigate
      symptom management with cannabis. Following Ethics Committee approval, HIV
      positive individuals attending a large clinic were recruited into an anonymous
      cross-sectional questionnaire study. Up to one-third (27%, 143/523) reported
      using cannabis for treating symptoms. Patients reported improved appetite (97%),
      muscle pain (94%), nausea (93%), anxiety (93%), nerve pain (90%), depression
      (86%), and paresthesia (85%). Many cannabis users (47%) reported associated
      memory deterioration. Symptom control using cannabis is widespread in HIV
      outpatients. A large number of patients reported that cannabis improved symptom
      control.

PMID- 15857740
TI  - Fast, systematic, and continuous delirium assessment in hospitalized patients:
      the nursing delirium screening scale.
AB  - Because no rigorously validated, simple yet accurate continuous delirium
      assessment instrument exists, we developed the Nursing Delirium Screening Scale
      (Nu-DESC). The Nu-DESC is an observational five-item scale that can be completed
      quickly. To test the validity of the Nu-DESC, 146 consecutive hospitalized
      patients from a prospective cohort study were continuously assessed for delirium
      symptoms by bedside nurses using the Nu-DESC. Psychometric properties of Nu-DESC
      screening were established using 59 blinded Confusion Assessment Method (CAM)
      ratings made by research nurses and psychiatrists. DSM-IV criteria and the
      Memorial Delirium Assessment Scale (MDAS) were rated along with CAM assessments.
      Analysis of these data showed that the Nu-DESC is psychometrically valid and has
      a sensitivity and specificity of 85.7% and 86.8%, respectively. These values are
      comparable to those of the MDAS, a longer instrument. Nu-DESC and DSM-IV
      sensitivities were similar. The Nu-DESC appears to be well-suited for widespread
      clinical use in busy oncology inpatient settings and shows promise as a research
      instrument.

PMID- 15857741
TI  - Acustimulation wrist bands are not effective for the control of chemotherapy
      induced nausea in women with breast cancer.
AB  - This experiment examined the efficacy of an acustimulation wrist band for the
      relief of chemotherapy-induced nausea using a randomized three-arm clinical trial
      (active acustimulation, sham acustimulation, and no acustimulation) in 96 women
      with breast cancer who experienced nausea at their first chemotherapy treatment.
      Five outcomes related to wrist band efficacy (acute nausea, delayed nausea,
      vomiting, QOL, and total amount of antiemetic medication used) were examined. The
      five outcomes were examined separately using analysis of covariance controlling
      for age and severity of past nausea. There were no significant differences in any
      of these study measures among the three treatment conditions (P>0.1 for all).
      Study results do not support the hypothesis that acustimulation bands are
      efficacious as an adjunct to pharmacological antiemetics for control of
      chemotherapy-related nausea in female breast cancer patients.

PMID- 15857742
TI  - Measurement of QTc in patients receiving chronic methadone therapy.
AB  - Recent reports suggest that methadone may prolong the QTc interval and cause
      torsades de pointes. This study was conducted to evaluate the prevalence of QTc
      prolongation during oral methadone therapy and identify factors associated with
      prolongation. Patients receiving oral methadone as treatment for chronic pain or
      addiction were eligible for the study. One hundred four patients who were
      receiving > or = 20 mg methadone per day for > or = 2 weeks underwent
      electrocardiograms to measure QTc interval duration. Sixty-three (61%) patients
      were male and 63 (61%) were receiving methadone maintenance for opioid addiction.
      The mean (+/- SD) age was 45.3 +/- 9.4 years. The median (range) methadone dose
      was 110 mg/day (20-1200 mg/day); median (range) number of months on methadone was
      12.5 months (1-444 months). The median (range) QTc interval was 428 msec (396-494
      msec). Thirty-three percent had QTc prolongation (males 40%, females 20%;
      P=0.03). No patient had a QTc longer than 500 msec. Significant dose response was
      observed in males on methadone <12 months (rho=0.60, P=0.02). Our study suggests
      that methadone may prolong the QTc interval in specific subpopulations but poses
      little risk of serious prolongation.

PMID- 15857743
TI  - Are there phases to the vaso-occlusive painful episode in sickle cell disease?
AB  - The purpose of this study was to describe the pain experience of children with
      sickle cell disease who were hospitalized for vaso-occlusive painful episodes.
      The pain experience, and signs and symptoms prior to admission and during
      hospitalization, are presented in the context of whether there is evidence to
      support the existence of phases to a vaso-occlusive painful episode. Children
      were interviewed about the onset of the painful episode and were asked to
      describe their pain from the day of admission to the day of discharge from the
      hospital. They were also observed for the absence or presence of signs and
      symptoms associated with the painful vaso-occlusive episode. Findings from this
      study provide some evidence to support previous observations related to changes
      during the evolution of painful episodes that may be occurring in phases (e.g.,
      evolving, inflammatory, resolving), as previously described in adults and
      children. These phases had different names, although the concepts were similar.

PMID- 15857744
TI  - Validation of a modified version of the brief pain inventory for painful diabetic
      peripheral neuropathy.
AB  - Neuropathic pain is the focus of current clinical research, clinical
      identification, and treatment. It is unique from nociceptive pain and requires
      evaluation of the relevance and utility of common pain measures created for other
      painful conditions. This study evaluated the psychometric properties of a
      modified Brief Pain Inventory (BPI) for patients with painful diabetic peripheral
      neuropathy (BPI-DPN). Participants were patients with painful DPN (n=255)
      enrolled in a DPN Burden of Illness survey referred through 17 outpatient
      settings (primary care physicians, endocrinologists, neurologists, and
      anesthesiologists). Patients completed the BPI-DPN, and self-report measures of
      health-related quality of life, mood sleep, and healthcare utilization.
      Construct, criterion and discriminant validity, and internal consistency
      reliability were evaluated. Principal axis factoring with oblimin rotation
      revealed two interpretable factors (eigenvalues>1.0), consistent with most
      published BPI validation studies; a severity scale comprising the four BPI
      Severity items and an interference scale comprising the seven Interference items,
      which satisfied criteria for interpretability and model fit. Cronbach's alpha was
      high (0.94) for both scales. Mean pain Severity was highly correlated with Bodily
      Pain from the Medical Outcomes Study Short Form-12, version 2 (rs=0.63, P <
      0.001), the Pain/Discomfort item in the Euro-QoL (rs=0.58, P < 0.001), and a
      verbal rating scale measure of pain severity (rs=0.74, P < 0.001). Individual BPI
      DPN Interference domains were moderately correlated (rs's >0.5, P < 0.001) with
      analogous measures, and the Sleep Interference item had a high, significant
      association with the three primary Medical Outcome Study-Sleep scale subscales
      (rs's=0.66-71, P < 0.001). Worst Pain and Interference ratings were significantly
      associated with hospital utilization and outpatient visits due to DPN. These
      results replicate, in a pure peripheral neuropathic pain condition, the BPI
      psychometric characteristics documented in populations with nociceptive or mixed
      pain conditions. The BPI-DPN is a promising instrument in the evaluation of
      painful DPN.

PMID- 15857745
TI  - Adrenal insufficiency in intestinal obstruction from carcinomatosis peritonei--a
      factor of potential importance in symptom palliation.
AB  - Corticosteroids are used in the management of intestinal obstruction (IO) in
      carcinomatosis peritonei. There is considerable overlap in the symptoms
      experienced in IO and functional adrenal insufficiency (AI). The success of
      symptom palliation in IO may be related to the presence of AI. The aim of this
      preliminary study was to evaluate the incidence of functional adrenal
      insufficiency in patients with IO and its relation to clinical outcome and
      symptom control. Twenty-nine consecutive patients with IO and carcinomatosis
      peritonei from gastrointestinal cancers admitted to our inpatient service between
      January and October 2002 were analyzed. They were screened for AI using the short
      corticotropin stimulation test. Thirteen patients (45%) had functional AI.
      Differences in characteristics of patients with normal adrenal function (Group 1)
      and adrenal insufficiency (Group 2) were not statistically significant. Time
      taken to control symptoms in Group 2 was longer. Mean duration of hospitalization
      per month of survival was two times longer in Group 2 relative to Group 1 (7.9
      versus 4.0 days, P=0.011). Functional AI may be caused by cytokines produced in
      advanced cancer mediating direct adrenal suppression. Prompt corticosteroid
      therapy in the presence of AI may facilitate IO symptom palliation.

PMID- 15857746
TI  - "Beauty is only skin deep": prevalence of dermatologic disease on a palliative
      care unit.
AB  - Skin disease affects the palliative care patient population because of their
      immunosuppressed state and decreased mobility; however, the prevalence of skin
      disease in this population has not been studied. We collected dermatologic
      histories and examinations of patients admitted to a hospital-based tertiary
      palliative care unit. Repeat examinations were performed to assess the incidence
      of cutaneous disease, as well as the progression of existing conditions. Sixteen
      of 65 patients admitted during 9 consecutive weeks participated in regular
      examinations. Six patients developed decubitus ulcers or had progression of
      existing ulcers. Dermatitis, xerosis, and pruritus were common diagnoses. Six
      patients sustained cutaneous trauma. Of the 49 non-participating patients, 4
      developed decubitus ulcers, 1 had a drug reaction, and 3 had cutaneous
      infections. Palliative care patients are prone to developing decubitus ulcers and
      cutaneous infections. Aggressive control of systemic symptoms may exacerbate skin
      disease. Consideration of dermatologic conditions is an important factor in
      optimizing skin control in this population.

PMID- 15857747
TI  - Effect of 25-hydroxyl group orientation on biological activity and binding to the
      1alpha,25-dihydroxy vitamin D3 receptor.
AB  - The hormonal form of vitamin D, 1alpha,25-dihydroxyvitamin D(3) (1,25D),
      generates many biological actions by interactions with its nuclear receptor
      (VDR). The presence of a carbon-25 hydroxyl group is necessary for optimizing
      binding to the VDR. To examine the effect of spatial orientation of the 25
      hydroxyl, two pairs of 22,23-allene sidechain analogs were studied. The 22R
      orientation in analogs HR (52+/-2%) and LA (154+/-19%) resulted in higher
      affinity binding than the 22S orientation of analogs HQ (21+/-3%) and LB (3.5+/
      1.3%; 1,25D=100%). Limited trypsin proteolysis showed that 22R analogs induced
      VDR conformational changes better able to protect VDR from digestion than 22S
      analogs. 22R analogs were also able to induce gene transcription at 10-100-fold
      lower concentrations than 1,25D; 22S analogs were less effective. Analog LA was
      at least 10-fold more potent than 1,25D at inducing differentiation, while the
      other analogs were less potent. None of the analogs were as potent as 1,25D in
      promoting in vivo intestinal calcium absorption or bone calcium mobilization. LA
      was the most potent of the analogs but required 20-30-fold higher doses than
      1,25D. The 25-hydroxyl orientation combined with the 16,17-ene functionality of
      analog LA enhances its ability to interact with VDR and induce biological
      actions.

PMID- 15857748
TI  - Effects of FSH and 17beta-estradiol on the transactivation of estrogen-regulated
      promoters and cell proliferation in L cells.
AB  - In the present study, we analyzed human follicle-stimulating hormone (FSH)
      induced cell proliferation and transactivation of estrogen-sensitive reporter
      genes-in L cells stably expressing the human FSH receptor [L-(hFSHR(+)) cells].
      In order to dissect the signaling pathways involved in this process, L-(hFSHR(+))
      cells were transiently transfected with either the 3X-ERE-TAT-Luc or the ERE
      VitA2-TK-CAT reporter genes and treated with FSH or PKA activators (cholera
      toxin, forskolin and 8-Br-cAMP) in the presence or absence of various kinase
      inhibitors. We found that FSH and all PKA activators, specifically induced
      transactivation of both reporter genes. Transactivation of estrogen-sensitive
      genes by FSH or PKA activators were blocked (approximately 90%) by H89 (PKA
      inhibitor) and LY294002 but not by Wortmannin (PI3-K inhibitors), 4-OH-tamoxifen,
      ICI182,780 or SB203580 (p38 MAPK inhibitor); PD98059 (ERK1/2 inhibitor) partially
      (approximately 30%) blocked the FSH-mediated effect. The combination of FSH and
      estradiol resulted in a synergistic effect on transactivation as well as on cell
      proliferation, and this enhancement was attenuated by antiestrogens. We
      additionally analyzed the participation of the coactivators SRC-1 and cAMP
      response element binding protein (CREB)-binding protein (CBP) in FSH-evoked
      estrogen receptor (ER)-dependent transactivation; we found that CBP but not SRC-1
      potentiated FSH-induced transcriptional activation of both ER-sensitive
      reporters, being this effect stronger on the ERE-VitA2-TK-CAT than on the 3X-ERE
      TAT-Luc reporter. Thus, in L-(hFSHR(+)) cells FSH induces transcriptional
      activation of estrogen-sensitive genes through an A-kinase-triggered signaling
      pathway, using also to a lesser extent the ERK1/2 and p38 pathways. PI3-K is not
      apparently involved in this FSH-mediated process since LY294002, but not
      Wortmannin, specifically binds ERs and completely blocks estrogen action.
      Presumably, CBP cooperates with the ER on genes that contain estrogen responsive
      elements through mechanisms involving the participation of other proteins and/or
      basal transcription factors (e.g. CREB), which in turn mediate the
      transcriptional response of estrogen-sensitive reporter genes to FSH stimulation.

PMID- 15857749
TI  - HX531, a retinoid X receptor antagonist, inhibited the 9-cis retinoic acid
      induced binding with steroid receptor coactivator-1 as detected by surface
      plasmon resonance.
AB  - HX531 is a retinoid X receptor (RXR) antagonist that inhibits 9-cis retinoic acid
      induced neutrophilic differentiation of HL-60 cells. In order to elucidate the
      inhibitory mechanism of HX531, we have developed a novel ligand sensor assay for
      RXR in which the receptor-coactivator interaction is directly monitored using
      surface plasmon resonance (SPR) biosensor technology. A 20-mer peptide from
      steroid receptor coactivator-1 (SRC-1), containing nuclear receptor interaction
      motif LXXLL was immobilized on the surface of a BIAcore sensor chip. Injection of
      human recombinant RXR with or without 9-cis retinoic acid resulted in ligand
      dependent interaction with the SRC-1 peptide. Kinetic analysis revealed
      dissociation constants (KD) of 9-cis RA-preincubated RXR to SRC-1 was 5.92 x 10(
      8)M. Using this technique, we found that 1 microM HX531 reduced the ka value of
      liganded-RXR with SRC-1, suggesting that HX531 reduced the affinity of RXR to SRC
      1. This SPR assay system was applied to obtain quantitative kinetic data of RXR
      ligand binding to the SRC-1 peptide and the alteration of these data by
      antagonists.

PMID- 15857750
TI  - 5beta-Cholane activators of the farnesol X receptor.
AB  - The farnesoid X receptor (FXR) is activated by bile acids, natural agonists for
      this nuclear receptor. FXR-target genes play important roles in cholesterol and
      lipid metabolism. We have found that a series of 5beta-cholanic acid derivatives,
      even though without a hydroxyl group or any other substituent on the steroidal
      rings, can activate FXR more potently than hydroxylated bile acids in a reporter
      gene assay. The most potent compound among these derivatives, N-methyl-5beta
      glycocholanic acid (NMGCA), induces the formation of receptor/coactivator complex
      in a gel-shift assay and also increases the expression of FXR target genes in
      human hepatoma HepG2 cells. Furthermore, in rats, NMGCA causes hypolipidemic
      effects as well as induction of the FXR target genes in liver. Our results
      suggest that NMGCA and its derivatives are important FXR activators in the study
      of the physiological functions of FXR and are potentially useful as
      pharmaceutical agents for treatment of cholesterol and lipid-related diseases.

PMID- 15857751
TI  - Mutations in squirrel monkey glucocorticoid receptor impair nuclear
      translocation.
AB  - To identify the determinants of impaired glucocorticoid receptor (GR) signaling
      in a model of glucocorticoid resistance, cloned GR from Guyanese squirrel monkeys
      (gsmGR) was tagged with enhanced green fluorescent protein, and nuclear
      translocation was examined in transfected COS1 cells. In keeping with evidence
      that gsmGR transactivational competence is impaired, we found that nuclear
      translocation is likewise diminished in gsmGR relative to human GR (hGR).
      Experiments with GR chimeras revealed that replacement of the gsmGR ligand
      binding domain (LBD) with that from hGR increased translocation. Truncated gsmGR
      constructs lacking the LDB after amino acid 552 also showed increased
      translocation even in the absence of cortisol. Three back-mutations of gsmGR to
      hGR (Thr551Ser, Ala616Ser, and Ser618Ala) in the LBD confirmed that these amino
      acids play a role in diminished translocation.

PMID- 15857752
TI  - Rational proteomics IV: modeling the primary function of the mammalian 17beta
      hydroxysteroid dehydrogenase type 8.
AB  - Significant sequence homology has been detected between prokaryotic beta-ketoacyl
      [acyl carrier protein] reductases (BKR) and eukaryotic 17beta-hydroxysteroid
      dehydrogenases type 8 (17beta-HSD_8). Three-dimensional models of ternary
      complexes of human 17beta-HSD_8 with NAD cofactor and two chemically distinct
      substrates, the BKR substrate {CH3-(CH2)(12)-CO-CH(2)-CO-S-[ACP]} and the HSD
      substrate {estradiol} have been constructed (the atomic coordinates are available
      on request; e-mail: pletnev@hwi.buffalo.edu). The more extensive and specific
      interactions of 17beta-HSD_8 with the BKR substrate compared to interactions with
      estradiol raise a serious question about the enzyme's primary function in vivo
      and suggest that it is likely to be involved in the regulation of fatty acid
      metabolism rather than in the steroid-dependent activity that has been
      demonstrated in vitro.

PMID- 15857753
TI  - Inhibition of the 26S proteasome blocks progesterone receptor-dependent
      transcription through failed recruitment of RNA polymerase II.
AB  - In the present study, we investigated the involvement of protein degradation via
      the 26S proteasome during progesterone receptor (PR)-mediated transcription in T
      47D cells containing a stably integrated MMTV-CAT reporter construct (CAT0
      cells). Progesterone induced CAT and HSD11beta2 transcription while co-treatment
      with the proteasome inhibitor, MG132, blocked PR-induced transcription in a time
      dependent fashion. MG132 treatment also inhibited transcription of beta-actin and
      cyclophilin, but not two proteasome subunit genes, PSMA1 and PSMC1, indicating
      that proteasome inhibition affects a subset of RNA polymerase II (RNAP(II))
      regulated genes. Progesterone-mediated recruitment of RNAP(II) was blocked by
      MG132 treatment at time points later than 1 h that was not dependent on the
      continued presence of PR, associated cofactors, and components of the general
      transcription machinery, supporting the concept that proteasome-mediated
      degradation is needed for continued transcription. Surprisingly, progesterone
      mediated acetylation of histone H4 was inhibited by MG132 with the concomitant
      recruitment of HDAC3, NCoR, and SMRT. We demonstrate that the steady-state
      protein levels of SMRT and NCoR are higher in the presence of MG132 in CAT0
      cells, consistent with other reports that SMRT and NCoR are targets of the 26S
      proteasome. However, inhibition of histone deacetylation by trichostatin A (TSA)
      treatment or SMRT/NCoR knockdown by siRNA did not restore MG132-inhibited
      progesterone-dependent transcription. Therefore, events other than histone
      deacetylation and stability of SMRT and NCoR must also play a role in inhibition
      of PR-mediated transcription.

PMID- 15857754
TI  - Role of the proteasome in the regulation of estrogen receptor alpha turnover and
      function in MCF-7 breast carcinoma cells.
AB  - Estrogen receptor alpha (ER) turnover in MCF-7 cells was assessed by pulse chase
      analysis and measurement of ER steady-state level. In untreated cells,
      degradation of (35)S-labeled ER was characterized by a slow phase followed by a
      more rapid decline. Without ligand, ER elimination was totally compensated by
      synthesis which maintained receptor homeostasis. Estradiol (E(2)) and the pure
      antiestrogen RU 58,668 abolished the slow phase of ER breakdown and enhanced the
      degradation of neosynthesized ER, producing a low ER steady-state level. By
      contrast, the partial antiestrogen OH-Tam was ineffective in this respect and
      caused ER accumulation. Regardless of the conditions, ER breakdown was abolished
      by proteasome inhibition (MG-132). ER ligands decreased cell capacity to bind
      [(3)H]E(2), even in the presence of MG-132, indicating that the regulation of ER
      level and E(2) binding capacity occurs through distinct mechanisms. MG-132
      partially blocked the basal transcription of an ERE-dependent reporter gene and
      modified the ability of E(2) to induce the expression of the latter: the hormone
      was unable to restore the transactivation activity measured without MG-132. RU
      58,668 and OH-Tam failed to enhance the inhibitory action of MG-132, suggesting
      that a loss of basal ER-mediated transactivation mainly affects the stimulatory
      effect of estrogens. Overall, our findings reveal that ER steady state level,
      ligand binding capacity and transactivation potency fit in a complex regulatory
      scheme involving distinct mechanisms, which may be dissociated from each other
      under various treatments.

PMID- 15857755
TI  - Differential effects of estrogens and progestins on the anticoagulant tissue
      factor pathway inhibitor in the rat.
AB  - Oral contraceptives (OC) and postmenopausal hormone therapy (HT) modulate plasma
      levels of proteins that regulate blood coagulation. It remains unclear whether
      the progestin component contributes to these changes. The present study was
      designed to determine whether progestins modulate two essential plasma
      anticoagulants, antithrombin (AT) and tissue factor pathway inhibitor (TFPI), in
      an animal model. Ovariectomized rats were treated orally with three progestins,
      norethindrone acetate (NETA), trimegestone (TMG), or drospirenone (DSP), either
      alone or combined with 17alpha-ethyinylestradiol (EE). Plasma AT levels were
      unchanged. However, TFPI activity was reduced by EE alone (10-100 microg/kg/day)
      in a dose-dependent manner; NETA (3 or 10 mg/kg/day) reduced TFPI by
      approximately 40 or approximately 80%, respectively, while TMG and DSP had no
      effect. NETA and EE effects were blocked by co-administration of ICI-182,780, an
      estrogen receptor antagonist, suggesting that both responses were likely estrogen
      receptor-mediated. Reduced TFPI after NETA or EE treatment was not accompanied by
      changes in TFPI mRNA levels in tissues that express TFPI, but there was a
      positive correlation between plasma TFPI and total cholesterol. Sex hormone
      effects on TFPI in this model and as reported in women may help to shift the
      coagulation balance to a more prothrombotic state. Progestins such as TMG and DSP
      that lack estrogenic activity could potentially have an improved clinical
      profile.

PMID- 15857756
TI  - Effect of testosterone and steroids homologues on indolamines and lipid
      peroxidation in rat brain.
AB  - The purpose of the present study was to evaluate the effect of 4-pregnen-17
      hydroxy-3-one (A) and two steroids homologues: 3beta-acetoxy-5,16-pregnadien-20
      one (B) and 3beta-acetoxy-16alpha-17alpha-epoxy-4-pregnen-20-one (C). Male Wistar
      rats were treated with o-cresol combined (A, B or C) steroids. Lipid peroxidation
      status as result of measurement reactive substances to thiobarbituric acid
      (TBARS) as well as serotonin (5-HT) and its precursor 5-hydroxytryptophan (5-HTP)
      were measured. The prostate glands were weighed, the 5alpha-reductase activity
      was determined. The animals treated with A, B, and C steroids showed a slight
      increase in both 5alpha-reductase activity and prostate size. 5-HT and 5-HTP
      levels did not change significantly, and TBARS showed an increase in the group
      treated with B steroid and a decrease in the A steroid group with significant
      differences in both groups (p<0.05) versus control group. Results suggest that A
      steroid reduces TBARS in rat brain, perhaps as a result of the interaction
      between the testosterone unsaturated carbons and OH(-) groups with free radicals.

PMID- 15857757
TI  - Analysis of the estrogenic components in kudzu root by bioassay and high
      performance liquid chromatography.
AB  - The estrogenic activity of the Chinese herb kudzu root was investigated by a
      recombinant yeast screening assay (YES). Isoflavones are the main components in
      the plant, of which puerarin is the most abundant one. The kudzu root extract was
      separated into four fractions according to the polarity. The crude extract and
      its sub-fractions, except the water fraction, showed clear estrogenic activity
      and the potencies were in the range of 10(-3) to 10(-1)g/l. The ligand potency
      was used to compare the estrogenic activity of these fractions. The crude extract
      and its sub-fractions were further analyzed by high performance liquid
      chromatography (HPLC) to correlate the activity and the active components.
      Bioassay and chemical analysis showed that theoretical estrogenic activity
      expressed as equivalent 17beta-estradiol concentration or the cumulative effects
      are comparable to that experimentally determined by YES. The results showed that
      the high content of isoflavones as well as the high estrogenic activity could
      make kudzu root extract an interesting candidate for hormone replacement therapy.

PMID- 15857758
TI  - Regulation of chitin synthesis in the larval midgut of Manduca sexta.
AB  - In insects, chitin is not only synthesized by ectodermal cells that form
      chitinous cuticles, but also by endodermal cells of the midgut that secrete a
      chitinous peritrophic matrix. Using anti-chitin synthase (CHS) antibodies, we
      previously demonstrated that in the midgut of Manduca sexta, CHS is expressed by
      two cell types, tracheal cells forming a basal tracheal network and columnar
      cells forming the apical brush border [Zimoch and Merzendorfer, 2002, Cell Tissue
      Res. 308, 287-297]. Now, we show that two different genes, MsCHS1 and MsCHS2,
      encode CHSs of midgut tracheae and columnar cells, respectively. To investigate
      MsCHS2 expression and activity in the course of the larval development, we
      monitored chitin synthesis, enzyme levels as well as mRNA amounts. All of the
      tested parameters were significantly reduced during molting and in the wandering
      stage when compared to the values obtained from intermolt feeding larvae. By
      contrast, MsCHS1 appeared to be inversely regulated because its mRNA was
      detectable only during the molt at the time when tracheal growth occurs at the
      basal site of the midgut. To further examine midgut chitin synthesis, we measured
      enzyme activity in crude midgut extracts and different membrane fractions. When
      we analysed trypsin-mediated proteolytic activation, a phenomenon previously
      reported for insect and fungal systems, we recognized that midgut chitin
      synthesis was only activated in crude extracts, but not in the 12,000 g membrane
      fraction. However, proteolytic activation by trypsin in the 12,000 g membrane
      fraction could be reconstituted by re-adding a soluble fraction, indicating that
      limited proteolysis affects an unknown soluble factor, a process that in turn
      activates chitin synthesis.

PMID- 15857759
TI  - Chitin synthase genes in Manduca sexta: characterization of a gut-specific
      transcript and differential tissue expression of alternately spliced mRNAs during
      development.
AB  - Chitin, the linear homopolymer of beta-1,4-linked N-acetylglucosamine, is
      produced by the enzyme chitin synthase (CHS). In general, this insoluble
      polysaccharide is found in two major extracellular structures in insects, the
      cuticle that overlays the epidermis and the peritrophic membrane (PM) that lines
      the midgut. Based on amino acid sequence similarities, insect CHSs are divided
      into two classes, A and B, and to date no more than two CHS genes have been
      identified in any single insect species. In species where both CHSs have been
      identified, one class A CHS and one class B CHS are always present. This finding
      suggests that these two genes may encode enzymes that synthesize chitin in
      different epithelial tissues. In our laboratory, we previously characterized
      transcripts for a class A CHS gene (MsCHS1) from the tobacco hornworm, Manduca
      sexta. We observed the expression of this gene in the larval epidermis,
      suggesting that the encoded enzyme functions to synthesize cuticular chitin. In
      this paper, we characterize a second chitin synthase gene (MsCHS2) belonging to
      class B and its cDNA from Manduca and show that it is expressed only in the
      midgut. This cDNA contains an open reading frame of 4575 nucleotides, which
      encodes a conceptual protein that is 1524 amino acids in length and is predicted
      to contain 16 transmembrane spans. Northern blot analysis of RNA isolated from
      anterior, medial, and posterior sections of the midgut from feeding larvae
      indicate that MsCHS2 is primarily expressed in the anterior midgut, with
      transcript levels tapering off in the medial and posterior midgut. Analysis of
      the MsCHS2 gene sequence indicates the absence of an alternate exon in contrast
      to the MsCHS1 gene, which yields two transcripts, MsCHS1a and MsCHS1b. RT-PCR
      analysis of the differential expression of these alternately spliced transcripts
      reveals that both splice variants are present in the epidermis. However, the
      ratio of the two alternately spliced transcripts varies during development, with
      MsCHS1a being generally more predominant. Southern blot analysis using a probe
      specific for CHS indicated that Manduca has only two CHS genes, akin to other
      insect species. Results from an analysis of expression of both genes in different
      tissues and developmental times indicate that the MsCHS1 enzyme is used for the
      synthesis of chitin in the cuticle and tracheae, whereas MsCHS2 is utilized
      exclusively for the synthesis of PM-associated chitin in the midgut.

PMID- 15857760
TI  - Molecular characterization of a cDNA encoding prophenoloxidase and its expression
      in Apis mellifera.
AB  - Phenoloxidase (PO), a melanin-synthesizing enzyme known to play an important role
      in insect defense, is found as a zymogen (ProPO) in hemolymph and cuticle, where
      it is activated by proteolysis. We characterized the first proPO cDNA in an
      eusocial insect, the Apis mellifera honey bee. The AmproPO cDNA contains an ORF
      of 2079 bp encoding 693 amino acids, and is composed of 9 exons and 8 introns.
      Southern blot of digested genomic DNA suggested that only one copy of the proPO
      gene is present in A. mellifera. The molecular mass of the deduced ProPO and the
      active enzyme was predicted to be 80.1 and 74.4 kDa, respectively. The calculated
      pI was 6.28. BLASTp search of the deduced amino acid sequence, and neighbor
      joining analysis, showed similarity with ProPOs from other insects, ranging from
      47% to 63%. Protein signature analyses revealed four conserved regions, including
      the two copper binding sites characteristic of arthropod ProPOs. RT-PCR and
      Southern blot showed the highest amount of AmproPO transcripts in workers whole
      body, followed by queens and drones. Expression was also detected in hemocytes
      and integument. Real time RT-PCR showed higher amounts of AmproPO transcripts in
      adults and older pupae than in younger pupae and larvae, suggesting a function of
      AmproPO in adult exoskeleton melanization and differentiation.

PMID- 15857761
TI  - Unique features of the structural model of 'hard' cuticle proteins: implications
      for chitin-protein interactions and cross-linking in cuticle.
AB  - Cuticular proteins are one of the determinants of the physical properties of
      cuticle. A common consensus region (extended R&R Consensus) in these proteins
      binds to chitin, the other major component of cuticle. We previously predicted
      the preponderance of beta-pleated sheet in the consensus region and proposed its
      responsibility for the formation of helicoidal cuticle (Iconomidou et al., Insect
      Biochem. Mol. Biol. 29 (1999) 285). Subsequently, we verified experimentally the
      abundance of antiparallel beta-pleated sheet in the structure of cuticle proteins
      (Iconomidou et al., Insect Biochem. Mol. Biol. 31 (2001) 877). Homology modelling
      of soft (RR-1) cuticular proteins using bovine plasma retinol binding protein
      (RBP) as a template revealed an antiparallel beta-sheet half-barrel structure as
      the basic folding motif (Hamodrakas et al., Insect Biochem. Molec. Biol. 32
      (2002) 1577). The RR-2 proteins characteristic of hard cuticle, have a far more
      conserved consensus and frequently more histidine residues. Extension of
      modelling to this class of consensus, in this work, reveals in detail several
      unique features of the proposed structural model to serve as a chitin binding
      structural motif, thus providing the basis for elucidating cuticle's overall
      architecture and chitin-protein interactions in cuticle.

PMID- 15857762
TI  - Expression of nuclear receptor-transcription factor genes during Aedes aegypti
      midgut metamorphosis and the effect of methoprene on expression.
AB  - Exposure of mosquito 4th instars to the juvenile hormone analogue methoprene
      prevents the emergence of adults by interfering with metamorphosis. One
      metamorphic processes that is disrupted is midgut remodeling. To investigate the
      molecular mechanisms by which this occurs, the pattern of transcription factor
      gene expression during the Aedes aegypti (L.) 4th instar was investigated by the
      method of real time PCR. The results indicate that in untreated larvae,
      expression of transcription factors genes AHR3 and AaE75B increases within 24h
      after the last larval-larval molt, transcription of AaEcR-B, AaUSP-a and AassFTZ
      F1 increases approximately 24h later, and transcription of AaE75A increases just
      before the larval-pupal molt. There is uniform expression of AaUSP-b throughout
      the 4th instar. The effect of methoprene exposure on transcription factor gene
      expression during midgut remodeling was investigated. The results indicate that,
      in a dose and stage dependent manner, methoprene affects increases in expression
      that normally occur during midgut remodeling. The coincident effects of
      methoprene on metamorphic midgut remodeling and on transcription factor gene
      expression suggests that the two processes are related.

PMID- 15857763
TI  - Comparative study of sex pheromone composition and biosynthesis in Helicoverpa
      armigera, H. assulta and their hybrid.
AB  - Two Helicoverpa species, H. armigera and H. assulta use (Z)-11-hexadecenal and
      (Z)-9-hexadecenal as their sex attractant pheromone components but in opposite
      ratios. Since both female and male interspecific hybrids produced by female H.
      assulta and male H. armigera have been obtained in our laboratory, we can make a
      comparative study of sex pheromone composition and biosynthesis in the two
      species and their hybrid. With GC and GC-MS analyses using single gland extracts,
      the ratio of (Z)-9-hexadecenal to (Z)-11-hexadecenal was determined as 2.1:100 in
      H. armigera, and 1739:100 in H. assulta. The hybrid has a ratio of 4.0: 100,
      which is closer to that of H. armigera, but significantly different from H.
      armigera. We investigated pheromone biosynthesis with labeling experiments, using
      various fatty acid precursors in H. armigera, H. assulta and the hybrid. In H.
      armigera, (Z)-11-hexadecenal is produced by delta11 desaturation of palmitic
      acid, followed by reduction and terminal oxidation; (Z)-9-hexadecenal results
      from delta11 desaturation of stearic acid, followed by one cycle of chain
      shortening, reduction and terminal oxidation. delta11 desaturase is the unique
      desaturase for the production of the two pheromone components. In our Chinese
      strain of H. assulta, palmitic acid is used as the substrate to form both the
      major pheromone component, (Z)-9-hexadecenal and the minor one, (Z)-11
      hexadecenal. Our data suggest that delta9 desaturase is the major desaturase, and
      delta11 desaturase is responsible for the minor component in H. assulta, which is
      consistent with previous work. However, the weak chain shortening acting on (Z)-9
      and (Z)-11-octadecenoic acid, which is present in the pheromone glands, does
      occur in this species to produce (Z)-7 and (Z)-9-hexadecenoic acid. In the
      hybrid, the major pheromone component, (Z)-11-hexadecenal is produced by delta11
      desaturation of palmitic acid, followed by reduction and terminal oxidation. The
      direct fatty acid precursor of the minor component, (Z)-9-hexadecenoic acid is
      mainly produced by delta9 desaturation of palmitic acid, but also by delta11
      desaturation of stearic acid and one cycle of chain shortening. The greater
      relative amounts of (Z)-9-hexadecenal in the hybrid are due to the fact that both
      palmitic and stearic acids are used as substrates, whereas only stearic acid is
      used as substrate in H. armigera. The evolutionary relationships between the
      desaturases in several Helicoverpa species are also discussed in this paper.

PMID- 15857764
TI  - BmiGI: a database of cDNAs expressed in Boophilus microplus, the
      tropical/southern cattle tick.
AB  - We used an expressed sequence tag approach to initiate a study of the genome of
      the southern cattle tick, Boophilus microplus. A normalized cDNA library was
      synthesized from pooled RNA purified from tick larvae which had been subjected to
      different treatments, including acaricide exposure, heat shock, cold shock, host
      odor, and infection with Babesia bovis. For the acaricide exposure experiments,
      we used several strains of ticks, which varied in their levels of susceptibility
      to pyrethroid, organophosphate and amitraz. We also included RNA purified from
      samples of eggs, nymphs and adult ticks and dissected tick organs. Plasmid DNA
      was prepared from 11,520 cDNA clones and both 5' and 3' sequencing performed on
      each clone. The sequence data was used to search public protein databases and a
      B. microplus gene index was constructed, consisting of 8270 unique sequences
      whose associated putative functional assignments, when available, can be viewed
      at the TIGR website (http://www.tigr.org/tdb/tgi). A number of novel sequences
      were identified which possessed significant sequence similarity to genes, which
      might be involved in resistance to acaricides.

PMID- 15857765
TI  - Hydrolysis of pyrethroids by carboxylesterases from Lucilia cuprina and
      Drosophila melanogaster with active sites modified by in vitro mutagenesis.
AB  - The cloned genes encoding carboxylesterase E3 in the blowfly Lucilia cuprina and
      its orthologue in Drosophila melanogaster were expressed in Sf9 cells transfected
      with recombinant baculovirus. Resistance of L. cuprina to organophosphorus
      insecticides is due to mutations in the E3 gene that enhance the enzyme's ability
      to hydrolyse insecticides. Previous in vitro mutagenesis and expression of these
      modifications (G137D, in the oxyanion hole and W251L, in the acyl pocket) have
      confirmed their functional significance. We have systematically substituted these
      and nearby amino acids by others expected to affect the hydrolysis of pyrethroid
      insecticides. Most mutations of G137 markedly decreased pyrethroid hydrolysis.
      W251L was the most effective of five substitutions at this position. It increased
      activity with trans permethrin 10-fold, and the more insecticidal cis permethrin
      >130-fold, thereby decreasing the trans:cis hydrolysis ratio to only 2, compared
      with >25 in the wild-type enzyme. Other mutations near the bottom of the
      catalytic cleft generally enhanced pyrethroid hydrolysis, the most effective
      being F309L, also in the presumptive acyl binding pocket, which enhanced trans
      permethrin hydrolysis even more than W251L. In these assays with racemic 1RS cis
      and 1RS trans permethrin, two phases were apparent, one being much faster
      suggesting preferential hydrolysis of one enantiomer in each pair as found
      previously with other esterases. Complementary assays with individual enantiomers
      of deltamethrin and the dibromo analogue of cis permethrin showed that the wild
      type and most mutants showed a marked preference for the least insecticidal 1S
      configuration, but this was reversed by the F309L substitution. The W251L/F309L
      double mutant was best overall in hydrolysing the most insecticidal 1R cis
      isomers. The results are discussed in relation to likely steric effects on enzyme
      substrate interactions, cross-resistance between pyrethroids and malathion, and
      the potential for bioremediation of pyrethroid residues.

PMID- 15857766
TI  - Molecular characterization of four midgut aminopeptidase N isozymes from the
      cabbage looper, Trichoplusia ni.
AB  - Four aminopeptidase N (APN) isoforms, TnAPN1, TnAPN2, TnAPN3 and TnAPN4, were
      identified from the cabbage looper, Trichoplusia ni, by cDNA cloning. The deduced
      amino acid sequences of the four APNs indicate that TnAPN1, TnAPN2, TnAPN3 and
      TnAPN4 are synthesized as pre-proteins of 110, 106, 114 and 108 kDa,
      respectively. Sequence features of the T. ni APNs include the presence of a
      signal peptide at their N-termini and a prepeptide at the C-termini for the GPI
      anchor, the zinc binding/gluzincin motif HEX2HX18E, the gluzincin aminopeptidase
      motif GAMENWG and the presence of glycosylation sites. After removal of the
      signal peptide and the C-terminal prepeptide, the predicted molecular weights of
      TnAPN1, TnAPN2, TnAPN3 and TnAPN4 are 106, 102, 110 and 104 kDa, respectively.
      Enzymatic activity assays of various larval tissues showed that aminopeptidase
      activities were mainly localized in the midgut and the specific enzyme activity
      per mg of midgut tissue proteins was constant in T. ni larvae regardless of the
      composition of dietary proteins and amino acids. Both enzyme activity assays and
      RT-PCR analyses for the expression of the APN genes in T. ni larval tissues
      demonstrated that APN genes were expressed in Malphigian tubules in addition to
      the midgut, which was the first observation that APNs were also synthesized in
      insect Malphigian tubules. The finding of APN gene expression and enzyme activity
      in the Malphigian tubules indicated the biochemical and functional similarity of
      the insect Malphigian tubules to the mammalian counterpart, the kidney, in which
      APNs are known to play important functions.

PMID- 15857767
TI  - Sex pheromone biosynthesis in Ostrinia zaguliaevi, a congener of the European
      corn borer moth O. nubilalis.
AB  - In order to clarify the biochemical basis to the divergence of sex pheromones in
      the genus Ostrinia (Lepidoptera: Crambidae), the pheromone biosynthetic pathway
      in O. zaguliaevi, a close relative of the European corn borer O. nubilalis, was
      investigated. Deuterium-labeled hexadecanoic or tetradecanoic acids were
      topically applied to the surface of the pheromone gland, and the incorporation of
      the label into pheromone components and their putative precursors was determined.
      It was suggested that the two components shared by O. zaguliaevi and O.
      nubilalis, (E)-11- and (Z)-11-tetradecenyl acetates, are biosynthesized from
      hexadecanoic acid through one round of chain shortening, Delta11 desaturation,
      reduction, and acetylation. An additional component specifically found in O.
      zaguliaevi, (Z)-9-tetradecenyl acetate, is likely to be produced by delta11
      desaturation of hexadecanoic acid, one round of chain shortening, reduction, and
      acetylation. Non-production of (Z)-9-tetradecenyl acetate in O. nubilalis was
      suggested to be due to the blockage of chain shortening from (Z)-11-hexadecenoate
      to (Z)-9-tetradecenoate.

PMID- 15857769
TI  - Mosquito glucosamine-6-phosphate N-acetyltransferase: cDNA, gene structure and
      enzyme kinetics.
AB  - Mosquito midgut epithelial cells secrete digestive enzymes as well as components
      of the peritrophic matrix in response to blood-feeding. The peritrophic matrix is
      composed of proteins, glycoproteins and chitin fibrils in a proteoglycan matrix
      and may function to protect the midgut epithelium from mechanical damage and
      insult from pathogens and toxins. Chitin biosynthesis takes place via the
      hexosamine pathway converting fructose-6-phosphate to UDP-N-acetylglucosamine,
      which is then polymerized to chitin by chitin synthase. Glucosamine-6-phosphate N
      acetyltransferase (GNA) is one of the hexosamine pathway enzymes and catalyzes
      the transfer of the acetyl group from acetyl-CoA to the primary amine of
      glucosamine-6-phosphate. We cloned and sequenced the GNA cDNA, gene (AeGna) and
      its putative promoter regions from Aedes aegypti. AeGna consists of five exons
      and four introns and lacks a TATA box near the transcription start site. The
      AeGna cDNA is 1.3 kb in length and the predicted protein is approximately 23.6
      kDa. The amino acid sequence of AeGna has high homology to its orthologues. AeGna
      mRNA is constitutively expressed in all developmental stages and blood-feeding
      causes no obvious effect on levels of AeGna transcript in the midgut. The Km
      value of recombinant GNA for glucosamine-6-phosphate was 330 microM and the Km
      for acetyl-CoA was 500 microM.

PMID- 15857770
TI  - Probing bacterial interactions: integrated approaches combining atomic force
      microscopy, electron microscopy and biophysical techniques.
AB  - Recent developments in the application of Atomic Force Microscopy (AFM) and other
      biophysical techniques for the study of bacterial interactions and adhesion are
      discussed in the light of established biological and microscopic approaches.
      Whereas molecular-biological techniques combined with electron microscopy allow
      the identification and localization of surface constituents mediating bacterial
      interactions, with AFM it has become possible to actually measure the forces
      involved in bacterial interactions. Combined with the flexibility of AFM in
      probing various types of physical interactions, such as electrostatic
      interactions, specific ligand-receptor interactions and the elastic forces of
      deformation and extension of bacterial surface polymers and cell wall, this
      provides prospects for the elucidation of the biophysical mechanism of bacterial
      interaction. However, because of the biochemical and a biophysical complexity of
      the bacterial cell wall, integrated approaches combining AFM with electron
      microscopy and biophysical techniques are needed to elucidate the mechanism by
      which a bacterium interacts with a host or material surface. The literature on
      electron microscopy of the bacterial cell wall is reviewed, with particular
      emphasis on the staining of specific classes of cell-wall constituents. The
      application of AFM in the analysis of bacterial surfaces is discussed, including
      AFM operating modes, sample preparation methods and results obtained on various
      strains. For various bacterial strains, the integration of EM and AFM data is
      discussed. Various biophysical aspects of the analysis of bacterial surface
      structure and interactions are discussed, including the theory of colloidal
      interactions and Bell's theory of cell-to-cell adhesion. An overview is given of
      biophysical techniques used in the analysis of the properties of bacterial
      surfaces and bacterial surface constituents and their integration with AFM.
      Finally, we discuss recent progress in the understanding of the role of bacterial
      interactions in medicine within the framework of the techniques and concepts
      discussed in the paper.

PMID- 15857768
TI  - Manduca sexta prophenoloxidase activating proteinase-1 (PAP-1) gene:
      organization, expression, and regulation by immune and hormonal signals.
AB  - Insect phenoloxidase (PO) participates in melanotic encapsulation, wound healing,
      and cuticle sclerotization. It is converted from prophenoloxidase (proPO) by a
      proPO-activating proteinase (PAP). Manduca sexta PAP-1, the final component of a
      serine proteinase cascade, cleaves proPO to generate active PO. In an effort to
      understand the transcriptional regulation, we isolated a genomic clone of the PAP
      1 gene, determined its nucleotide sequence, and elucidated its exon-intron
      organization. Computer analysis revealed several immune and hormone responsive
      elements in the upstream region. Southern blot analysis suggested that the M.
      sexta genome contains a single copy of PAP-1 gene. Reverse transcription
      polymerase chain reaction showed that PAP-1 was constitutively expressed in fat
      body, trachea, and nerve tissue of the fifth instar larvae. The mRNA levels in
      hemocytes and fat body markedly increased in response to a bacterial challenge.
      We also observed tissue-specific and developmental regulation of the gene's
      transcription. Treating M. sexta fat body culture with 20-hydroxyecdysone reduced
      the PAP-1 mRNA level. These data indicated that the expression of PAP-1 gene is
      under the dual control of immune and hormonal signals.

PMID- 15857771
TI  - Simultaneous in situ profiling of DNA lesion endpoints based on image cytometry
      and a single cell database approach.
AB  - Analyzing the integrity of DNA is one of the most frequent used endpoints for
      risk assessment of chemical and physical agents. In the framework of a
      radiobiological space experiment, this work aimed at having (1) a histochemical
      tool for the in situ assessment of DNA damage in as long as 20 days old fixed
      cell cultures, (2) a comprehensive tool for the quantification of different types
      of DNA lesions, and (3) a methodology of sampling thousands of nuclei based on
      confocal microscopy, automated stage scanning and digital image processing. For
      this purpose several fixatives and permeabilization techniques were tested
      together with the combinatorial use of terminal dUTP transferase-mediated nick
      end-labeling (TUNEL) and the DNA polymerase I mediated in situ nick translation.
      These biochemical tools are useful for scoring DNA single and double breaks, and
      oxidative lesions. Ltk(-) cells were exposed either to hydrogen peroxide or heavy
      ion beam irradiation. Combination of paraformaldehyde fixation, sodium citrate
      permeabilization and heat gave the best staining results. A three-channel
      fluorescence methodology was established including a DNA counter stain for
      nucleus identification and normalization of DNA content. Communication between
      confocal imaging software, image analysis software and a relational database
      proved to be pivotal for a semi-automated high-end single cell analysis and
      storage of images. In this way, DNA damage data per nucleus can be traced back to
      the original image. As much as 2500 cells could be analyzed in situ within a day
      and correlations drawn between different DNA lesion endpoints.

PMID- 15857773
TI  - Electron distribution on a tilted sample in the high pressure SEM.
AB  - The effect of the specimen inclination on the electron distribution at the
      specimen surface in an HPSEM was investigated by Monte Carlo simulation. A
      broadening of the electron profile versus the tilt angle was obtained and a
      relationship between the r(0.9) radius and this tilt angle is proposed. The plot
      of the electron distribution at the sample surface shows that the classical
      scattering profile in the standard conditions is modified so that an inclined
      truncated shape is obtained. This result confirms the difficulty to carry out X
      ray microanalysis in low vacuum conditions.

PMID- 15857772
TI  - Resolution and reproducibility of measures of the diameter of small collagen
      fibrils by transmission electron microscopy--application to the rabbit corneal
      stroma.
AB  - AIM: To assess the impact of measurements of different numbers of small collagen
      fibrils at different final magnification values on the resultant mean values for
      fibril diameter (FD). METHODS: Very high magnification (33,000x) electron
      micrographs were taken of the posterior-central zone of the corneal stroma from
      young adult rabbits (2 kg), printed at 46,000 or 50,000x, scanned at 400 d.p.i.
      and 35 mm slides prepared. These were projected to give final magnifications
      between 150,000x and 450,000x. An overlay of fibril outlines was prepared from
      the projected images and the fibril diameters (FD's) measured to within 0.5 mm.
      RESULTS: On the overlays, at different projection magnifications, the average
      FD's ranged from 4 to 13.5 mm to allow measures to be made at a real resolution
      of between 3.5 and 1 nm. Using a fixed sized region of interest (ROI) on the
      overlays, the average values of FD's ranged between 24.9 and 31.7 nm, and could
      vary (for any particular micrograph) by up to 3.6 nm according to the number of
      FD's measured (n=34-384/ROI). Using a fixed number of FD measures (n=100) at
      different projection magnifications yielded average FD values from different
      corneas of between 25.1 and 35.2 nm, which could vary by up to 4.3 nm depending
      on the magnification used. CONCLUSIONS: The results indicate that different
      average values for measures of fibril diameter of small collagen fibrils can
      easily be obtained according to the final magnification used and the number of
      fibrils measured, and that the overall averages can depend on whether the data
      sets are averaged or pooled. These aspects of the morphometry of small collagen
      fibrils therefore need to be carefully specified.

PMID- 15857774
TI  - Cytogenetics of the land snails Cantareus aspersus and C. mazzullii (Mollusca:
      Gastropoda: Pulmonata).
AB  - A cytogenetic study was carried out on the chromosomes and nuclear DNA contents
      of the land snails Cantareus aspersus and C. mazzullii (Gastropoda: Pulmonata).
      Chromosomes were studied using Giemsa staining, banding methods and fluorescent
      in situ hybridization (FISH) with three repetitive DNA probes [18S rDNA,
      (GATA)(n) and (TTAGGG)(n)]. Results were very similar in the two species both
      showing (1) 54 bi-armed chromosomes [submetacentrics (SM) + metacentrics (M) +
      subtelocentrics (ST)]; (2) 10 terminal NORs after sequential application of rDNA
      FISH and silver staining; (3) uniform DNA fluorescence with CMA(3) and DAPI
      staining and (4) genomic composition considerably enriched both in highly- and
      moderately-repeated DNAs. The telomeric (TTAGGG)(n) sequence hybridized with the
      termini of all of the chromosomes in the two species. In spite of their apparent
      karyological uniformity, flow cytometry DNA assays showed that C. aspersus and C.
      mazzullii are characterized by different nuclear DNA content (C values are 3.58
      and 3.08 pg, respectively) and slightly different base composition in their
      genomes. Present data on GS and AT% in C. mazzullii and C. aspersus confirm the
      trend toward high GS values and GC percentages among land snails.

PMID- 15857775
TI  - Ultrastructural characterization of the hemocytes of Culex quinquefasciatus
      (DIPTERA: Culicidae).
AB  - Six hemocytes cell types from Culex quinquefasciatus were identified by light and
      transmission electron microscopy: They are prohemocytes (9.3%), spherulocytes
      (1.6%), adipohemocytes (0.8%), oenocytoids (4.6%), plasmatocytes (43.4%) and
      granulocytes (40.3%). The prohemocytes were the smallest hemocytes encountered in
      the hemolymph, displaying a large and centrally located nucleus, almost filling
      the whole cell. The spherulocytes, which were small hemocytes, presented small
      and numerous spherules with a lamellar pattern and an electron-dense core. Rare
      adipohemocytes were observed in the C. quinquefasciatus hemolymph, presenting
      large nucleus with an evident nucleolus, cytoplasm containing rough endoplasmic
      reticulum (RER), mitochondriae and lipid inclusions. C. quinquefasciatus
      oenocytoids showed homogeneous cytoplasm with several granules, completely or
      partially filled with amorphous material. These cells showed abundant smooth
      endoplasmic reticulum (SER) and dense mitochondriae. By light microscopy analysis
      we identified two morphological types of plasmatocytes, granular and agranular.
      However, ultrastructural investigation revealed that the granular cells contained
      lipid inclusion between RER membranes, instead of membrane-bounded granules. The
      granulocytes presented a fusiform or circular profile and displayed a unique and
      very complex process of granules formation, including organization of polysomes
      inside vesicles that protrude from the Golgi system, synthesis of a proteinaceous
      material, condensation of the granule matrix and recycling of endoplasmic
      membranes. Intense endocytic pathways were also observed in the granulocytes.

PMID- 15857776
TI  - Analysis of extraterrestrial particles using monochromated electron energy-loss
      spectroscopy.
AB  - A monochromated (scanning) transmission electron microscope was used to analyze
      individual sub-micron grains within interplanetary dust particles (IDP). Using
      low-loss and core-loss electron energy-loss spectroscopy, we analyzed fluid and
      gas inclusions within vesiculated alumosilicate grains. It is shown that
      nanometer-sized vesicles contain predominantly molecular oxygen (O(2)) beside a
      small fraction of H(2)O. Low-loss spectra reveal the Schumann-Runge continuum
      peaking at 8.6 eV and absorption bands reflecting vibrational excitation states
      of O(2) molecules between the first (12.1 eV) and second (16.1 eV) ionization
      energy. The presence of oxygen gas is supported by the corresponding oxygen K
      edge fine structure. The valence state of Fe in iron-oxide within the IDP was
      also studied. Low-loss spectra provide qualitative information about the
      oxidation state of iron consistent with the Fe(2+)/Fe(3+) ratio quantitatively
      derived from the Fe L(2,3) edge.

PMID- 15857778
TI  - Directed evolution: selecting today's biocatalysts.
AB  - Directed evolution has become a full-grown tool in molecular biology nowadays.
      The methods that are involved in creating a mutant library are extensive and can
      be divided into several categories according to their basic ideas. Furthermore,
      both screening and selection can be used to target the enzyme towards the desired
      direction. Nowadays, this technique is broadly used in two major applications:
      (industrial) biocatalysis and research. In the first field enzymes are engineered
      in order to produce suitable biocatalysts with high catalytic activity and
      stability in an industrial environment. In the latter area methods are
      established to quickly engineer new enzymes for every possible catalytic step,
      thereby creating a universal biotechnological toolbox. Furthermore, directed
      evolution can be used to try to understand the natural evolutionary processes.
      This review deals with new mutagenesis and recombination strategies published
      recently. A full overview of new methods for creating more specialised mutant
      libraries is given. The importance of selection in directed evolution strategies
      is being exemplified by some current successes including the beta-lactam
      acylases.

PMID- 15857779
TI  - Directed evolution of biocatalytic processes.
AB  - The benefits of applying biocatalysts to organic synthesis, such as their high
      chemo-, regio-, and enantio-specificity and selectivity, must be seriously
      considered, especially where chemical routes are unavailable, complex or
      prohibitively expensive. In cases where a potential biocatalytic route is not yet
      efficient enough to compete with chemical synthesis, directed evolution, and/or
      process engineering could be implemented for improvements. While directed
      evolution has demonstrated great potential to enhance enzyme properties, there
      will always be some aspects of biocatalytic processes that it does not address.
      Even where it can be successfully applied, the resources required for its
      implementation must currently be weighed against the feasibility of, and
      resources available for developing a chemical synthesis route. Here, we review
      the potential of combining directed evolution with process engineering, and
      recent developments to improve their implementation. Favourable targets for the
      directed evolution of new biocatalysts are the syntheses of highly complex
      molecules, especially where chemistry, metabolic engineering or recombineering
      provide a partial solution. We also review some of the recent advances in the
      application of these approaches alongside the directed evolution of biocatalysts.

PMID- 15857780
TI  - Directed evolution of enzyme stability.
AB  - Modern enzyme development relies to an increasing extent on strategies based on
      diversity generation followed by screening for variants with optimised
      properties. In principle, these directed evolution strategies might be used for
      optimising any enzyme property, which can be screened for in an economically
      feasible way, even if the molecular basis of that property is not known.
      Stability is an interesting property of enzymes because (1) it is of great
      industrial importance, (2) it is relatively easy to screen for, and (3) the
      molecular basis of stability relates closely to contemporary issues in protein
      science such as the protein folding problem and protein folding diseases. Thus,
      engineering enzyme stability is of both commercial and scientific interest. Here,
      we review how directed evolution has contributed to the development of stable
      enzymes and to new insight into the principles of protein stability. Several
      recent examples are described. These examples show that directed evolution is an
      effective strategy to obtain stable enzymes, especially when used in combination
      with rational or semi-rational engineering strategies. With respect to the
      principles of protein stability, some important lessons to learn from recent
      efforts in directed evolution are (1) that there are many structural ways to
      stabilize a protein, which are not always easy to rationalize, (2) that proteins
      may very well be stabilized by optimizing their surfaces, and (3) that high
      thermal stability may be obtained without forfeiture of catalytic performance at
      low temperatures.

PMID- 15857781
TI  - Directed evolution of (betaalpha)(8)-barrel enzymes.
AB  - Natural molecular evolution supplies us with manifold examples of protein
      engineering. The imitation of these natural processes in the design of new
      enzymes has led to surprising and insightful results. Well-suited for design by
      evolutionary methods are enzymes with the common and versatile (betaalpha)(8)
      barrel fold. Studies of enzyme stability, folding and design as well as the
      evolution of (betaalpha)(8)-barrel enzymes are discussed.

PMID- 15857782
TI  - Directed evolution of novel polymerases.
AB  - DNA and RNA polymerases evolved to function in specific environments with
      specific substrates to propagate genetic information in all living organisms. The
      commercial availability of these polymerases has revolutionized the biotechnology
      industry, but for many applications native polymerases are limited by their
      stability or substrate recognition. Thus, there is great interest in the directed
      evolution of DNA and RNA polymerases to generate enzymes with novel, desired
      properties, such as thermal stability, resistance to inhibitors, and altered
      substrate specificity. Several screening and selection approaches have been
      developed, both in vivo and in vitro, and have been used to evolve polymerases
      with a variety of important activities. Both the techniques and the evolved
      polymerases are reviewed here, along with a comparison of the in vivo and in
      vitro approaches.

PMID- 15857783
TI  - High-throughput assays for lipases and esterases.
AB  - In the past few years a considerable number of high-throughput screening (HTS)
      systems have been developed, especially for lipases and esterases. In this
      review, a range of HTS methods for the directed evolution of these hydrolases are
      covered. This includes spectrophotometric and fluorimetric formats as well as
      other approaches to allow for fast, efficient and reliable identification of
      desired enzyme variants within large mutant libraries. In addition, methods for
      library creation and application of lipases and esterases are briefly covered.

PMID- 15857784
TI  - Mathematical expressions useful in the construction, description and evaluation
      of protein libraries.
AB  - The creation of protein libraries by random mutagenesis and cassette mutagenesis
      has proven to be a successful method of protein engineering. Appropriate
      statistical analysis is important for the proper construction of these libraries
      and even more important for the interpretation of data from these libraries. We
      present simple mathematical expressions useful in the creation and evaluation of
      such libraries. These equations are useful in estimating the distribution of
      mutations, the degeneracy of the library and the frequency of a particular clone
      in the library. In addition, general equations addressing the probability that a
      particular clone is in a library, the probability that a library is complete, and
      as the consequences of retransformation of the library on these probabilities are
      presented.

PMID- 15857786
TI  - Whole plasmid mutagenic PCR for directed protein evolution.
AB  - Protein function can be engineered through iterated cycles of random mutagenesis
      and screening (directed evolution). Optimization of protein expression is
      essential for the development of sensitive and precise high throughput assays.
      Here we optimize the performance of a plasmid-borne Escherichia coli lacZ gene in
      two rounds of directed evolution. First, its promoter was "randomized" by whole
      plasmid polymerase chain reaction (PCR) and intra-molecular self-ligation. A
      genetically stable constitutive expression vector was isolated in an in vivo
      genetic selection. Second, the entire plasmid was randomly mutated in a slightly
      mutagenic long polymerase chain reaction. The PCR products were digested with a
      restriction enzyme, self-ligated by T4 DNA ligase and transformed into E. coli.
      The resulting library of beta-galactosidase (beta-gal) mutants consisted mostly (
      approximately 80%) of hypomorphs, suggesting that the mutation rate was
      appropriate for directed evolution applications. We isolated and characterized 14
      variants with increased activity in reactions with 5-bromo-4-chloro-3-indolyl
      beta-d-galactopyranoside (X-gal). The purified protein derived from one clone
      exhibited a 100-fold improvement in k(cat) over its parent in reactions with para
      nitrophenyl-beta-d-galactopyranoside (pNP-gal). This latter result clearly
      demonstrates the utility of whole plasmid mutagenic PCR for directed protein
      evolution.

PMID- 15857785
TI  - Degenerate oligonucleotide gene shuffling (DOGS) and random drift mutagenesis
      (RNDM): two complementary techniques for enzyme evolution.
AB  - Improvement of the biochemical characteristics of enzymes has been aided by
      misincorporation mutagenesis and DNA shuffling. Many gene shuffling techniques
      result predominantly in the regeneration of unshuffled (parental) molecules. We
      describe a procedure for gene shuffling using degenerate primers that allows
      control of the relative levels of recombination between the genes that are
      shuffled, and reduces the regeneration of unshuffled parental genes. This
      shuffling procedure avoids the use of endonucleases for gene fragmentation prior
      to shuffling and allows the inclusion of random mutagenesis of selected portions
      of the chimeric genes as part of the procedure. We illustrate the use of the
      shuffling technique with a family of beta-xylanase genes that possess widely
      different G+C contents. In addition, we introduce a new method (RNDM) for rapid
      screening of mutants from libraries where no adaptive selection has been imposed
      on the cells. They are identified only by their retention of enzymatic activity.
      The combination of RNDM followed by DOGS allows a comprehensive exploration of a
      protein's functional sequence space.

PMID- 15857787
TI  - Engineering the substrate specificity of cytochrome P450 CYP102A2 by directed
      evolution: production of an efficient enzyme for bioconversion of fine chemicals.
AB  - The P450 cytochromes constitute a large family of hemoproteins that catalyze the
      monooxygenation of a diversity of hydrophobic substrates. CYP102A2 is a
      catalytically self-sufficient cytoplasmic enzyme from Bacillus subtilis,
      containing both a monooxygenase domain and a reductase domain on a single
      polypeptide chain. CYP102A2 was subjected to error-prone PCR to generate mutants
      with enhanced activity with fatty acids and other aromatic substrates. The
      library of CYP102A2 mutants was expressed in BL21(DE3) Escherichia coli cells and
      screened for their ability to oxidize different substrates by means of an
      activity assay. After a single round of error-prone PCR, the variant Pro15Ser
      exhibiting modified substrate specificity was generated. This variant showed
      approximately 6- to 9-fold increased activity with SDS, lauric acid and 1,4
      naphthoquinone, and enhanced activity for other substrates such as ethacrynic
      acid and epsilon-amino-n-caproic acid. Molecular modeling of the CYP102A2
      monooxygenase domain suggested that Pro15 is located in a short helical segment
      and is involved in extensive interactions between the N-terminal domain and the
      beta2 sheet, which contribute to the formation of the substrate binding site.
      Thus, Pro15 appears to affect substrate binding and catalysis indirectly. These
      results clearly demonstrate the importance of remote residues, not readily
      predicted by rational design, for the determination of substrate specificity. In
      addition, we report here that the Pro15Ser variant of CYP102A2 can be efficiently
      immobilized on epoxy-activated Sepharose at pH 8.5 and 4 degrees C. The
      immobilized variant of CYP102A2 retains most of its activity (81%) and shows
      improved stability at 37 degrees C. The approach offers the possibility of
      designing a P450 bioreactor that can be operated over a long period of time with
      high efficiency and which can be used in fine chemical synthesis.

PMID- 15857788
TI  - Directed evolution for engineering pH profile of endoglucanase III from
      Trichoderma reesei.
AB  - The potential of cellulase has been revealed not only in biomass conversion but
      also in various industrial processes, including food, textiles, laundry, pulp,
      and paper. Due to the need for alkali-tolerant cellulase with high specific
      activity at alkaline pH, for example, for application in detergent industry an
      error-prone PCR approach was employed for enhancing the alkali-tolerant ability
      of endoglucanase III (EG III) from Trichoderma reesei by error-prone PCR. One
      mutant (N321T) which exhibited an optimal activity at pH 5.4, corresponded to a
      basic shift of 0.6 pH unit compared to the wild-type enzyme, was selected and
      characterized. In addition, two site-directed mutations, N321D and N321H, were
      designed to study the role of residue at position 321. As expected, the N321D
      mutation changed enzyme's optimal activity to pH 4.0, resulting in a large
      decrease in the specific activity. However, the N321H mutated enzyme was active
      over a broader pH range compared to the wild type, with no much change in the
      specific activity. These properties suggest that the residue at position 321 is
      important amino acid residue in determining the pH activity profile of the EG III
      from T. reesei.

PMID- 15857789
TI  - Alteration of substrate specificity of aspartase by directed evolution.
AB  - Aspartase (l-aspartate ammonia-lyase, EC 4.3.1.1), which catalyzes the reversible
      deamination of l-aspartic acid to yield fumaric acid and ammonia, is highly
      selective towards l-aspartic acid. We screened for enzyme variants with altered
      substrate specificity by a directed evolution method. Random mutagenesis was
      performed on an Escherichia coli aspartase gene (aspA) by error-prone PCR to
      construct a mutant library. The mutant library was introduced to E. coli and the
      transformants were screened for production of fumaric acid-mono amide from l
      aspartic acid-alpha-amide. Through the screening, one mutant, MA2100, catalyzing
      deamination of l-aspartic acid-alpha-amide was achieved. Gene analysis of the
      MA2100 mutant indicated that the mutated enzyme had a K327N mutation. The
      characteristics of the mutated enzyme were examined. The optimum pH values for
      the l-aspartic acid and l-aspartic acid-alpha-amide of the mutated enzyme were pH
      8.5 and 6.0, respectively. The K(m) value and V(max) value for the l-aspartic
      acid of the mutated enzyme were 28.3 mM and 0.26 U/mg, respectively. The K(m)
      value and V(max) value for the l-aspartic acid-alpha-amide of the mutated enzyme
      were 1450 mM and 0.47 U/mg, respectively. This is the first report describing the
      alteration of the substrate specificity of aspartase, an industrially important
      enzyme.

PMID- 15857791
TI  - What is known about the epidemiology of the vasculitides?
AB  - The vasculitides are conditions of unknown aetiology. Until recently, relatively
      little was known about their incidence and prevalence, but there are now
      increasing data, especially from Europe. These are conditions of the extremes of
      age. Kawasaki disease occurs predominately in Asian children, with a peak annual
      incidence of 90/100,000 children aged under 5 years. Henoch-Schonlein purpura has
      an incidence of 70/100,000 in those aged 4-7 years and is also more common in
      Asians. Primary systemic vasculitis has a peak incidence 6/100,000 in those aged
      65-74 years. Giant cell arteritis is most common in Caucasians aged over 70
      years, with an incidence of 53/100,000. Vasculitis has been associated with
      malignancy, the association being strongest between haematological malignancies
      and cutaneous vasculitis. There is occasionally a temporal association; failure
      to respond appropriately to therapy should prompt a search for malignancy.
      Lesions suspicious of malignancy should be biopsied even if the diagnosis of
      vasculitis has been histologically proven.

PMID- 15857792
TI  - Classification and diagnostic criteria in systemic vasculitis.
AB  - Approximately 20 different primary forms of vasculitis are recognized, not all of
      which have been included in classification schemes or consensus statements
      regarding nomenclature. A variety of classification schemes have been proposed
      over the past 50 years, many predicated upon the size of the primary type of
      vessel involved in a given disease, as well as other considerations that include
      demographic features, organ tropism, the presence or absence of granulomatous
      inflammation, the role of immune complexes in pathophysiology and the association
      of autoantibodies with some forms of vasculitis. All classification schemes to
      date have had shortcomings owing to the substantial gaps in knowledge about
      vasculitis, but the American College of Rheumatology criteria for the
      classification of some forms of vasculitis are useful for the purpose of
      including patients in research studies. The Chapel Hill Consensus Conference has
      clarified some existing controversies in nomenclature of the systemic
      vasculitides. Robust diagnostic criteria for the various forms of vasculitis
      have, however, remained elusive.

PMID- 15857793
TI  - What is the best approach to diagnosing large-vessel vasculitis?
AB  - Temporal arteritis, including large-vessel giant cell arteritis, and Takayasu's
      arteritis are the two primary large-vessel vasculitides. Patients with temporal
      arteritis often present with headache, swollen temporal arteries, impairment of
      vision or symptoms of polymyalgia rheumatica. Clinical examination includes
      palpation of the temporal arteries and radial pulses, auscultation of the
      subclavian and axillary region, and fundoscopy. The presence of jaw claudication,
      diplopia and temporal artery abnormalities correlates with a high probability of
      positive histology. Duplex ultrasonography of the temporal arteries delineates a
      characteristic hypoechoic, oedematous wall swelling, stenoses and occlusions. It
      detects the same pathologies in the axillary arteries and other arteries in large
      vessel giant cell arteritis. Angiography, magnetic resonance imaging, magnetic
      resonance angiography, electron beam computed tomography, computed tomography
      angiography and positron emission tomography show characteristic changes in the
      aorta and its primary branches in large-vessel giant cell arteritis and
      Takayasu's arteritis. Takayasu's arteritis often begins with diffuse symptoms
      such as low-grade fever, arthralgia, fatigue and weight loss. Clinical
      examination is important to detect bruits, pulse reduction and blood pressure
      differences. Profound experience exists with angiography. Other imaging methods
      are interesting alternatives as they are less invasive and may depict the
      inflammatory wall swelling.

PMID- 15857794
TI  - Difficult to diagnose manifestations of vasculitis: does an interdisciplinary
      approach help?
AB  - In the early stages of disease, primary systemic vasculitides often present with
      non-specific symptoms that make early diagnosis a challenge. The variety of
      clinical manifestations found in systemic vasculitis is huge, and some
      manifestations are frequently not clinically overt at first presentation. A
      logical implication of the often non-specific and sometimes subclinical
      presentation of vasculitis is that a systematic diagnostic work-up is necessary.
      This requires a multidisciplinary approach involving the expert opinion of
      specialists from many disciplines, such as neurology, radiology, respiratory
      medicine, pathology and microbiology. There are no generally accepted diagnostic
      criteria for primary systemic vasculitides, and the application of classification
      criteria as diagnostic criteria is not feasible and may even be misleading. The
      demonstration of vasculitis on biopsy is still the gold standard for the
      diagnosis of vasculitis. In cases where biopsies cannot be obtained, surrogate
      parameters of vasculitis (e.g. glomerular hematuria or mononeuritis multiplex),
      along with serology and imaging, can support a clinical diagnosis of vasculitis.
      This review discusses the approach to the diagnosis of central nervous system and
      pulmonary manifestations of primary systemic vasculitis. These two examples of
      difficult to diagnose manifestations of vasculitis illustrate the necessity of an
      interdisciplinary approach to the diagnostic work-up.

PMID- 15857795
TI  - What do antineutrophil cytoplasmic antibodies (ANCA) tell us?
AB  - Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies directed against
      antigens found in the cytoplasmic granules of neutrophils and monocytes. ANCA
      testing is usually performed to help diagnose or exclude Wegener's granulomatosis
      and microscopic polyangiitis. The three most commonly used assays are indirect
      immunofluorescence (IIF) and the direct and 'capture' enzyme-linked immunosorbent
      assays (ELISAs) for ANCA directed against proteinase 3 (PR3) and myeloperoxidase
      (MPO). Although the International Consensus Statement for Testing and Reporting
      ANCA recommends that all sera are screened for ANCA by IIF and that IIF
      positivity is confirmed by direct ELISAs, some laboratories test by direct ELISA
      alone, others screen with direct ELISA and confirm positive sera by IIF, and a
      few use capture ELISAs. This chapter discusses the various forms of vasculitis
      associated with ANCA, the usefulness of each of the ANCA assays and how ANCA
      testing can be used in the management of patients with small-vessel vasculitis.

PMID- 15857796
TI  - Are steroids alone sufficient for the treatment of giant cell arteritis?
AB  - Glucocorticosteroids are the cornerstone of treatment of giant cell arteritis. An
      initial dose of prednisone or its equivalent of at least 40-60mg per day as
      single or divided dose is usually adequate. Glucocorticosteroids may prevent, but
      usually do not reverse, visual loss. A treatment course of 1-2 years is often
      required. Some patients, however, have a more chronic-relapsing course and may
      require low doses of glucocorticosteroids for several years. Glucocorticosteroid
      related adverse events are common. In studies on immunosuppressant agents,
      methotrexate has been used as a glucocorticosteroid-sparing drug with conflicting
      results. This drug may, however, be given to patients who need high doses of
      glucocorticosteroids to control active disease and who have serious side effects.
      A recent pilot study found that infliximab was efficacious in patients with
      glucocorticosteroid-resistant giant cell arteritis. However, randomized
      controlled trials are required to define the role of anti-tumor necrosis factor
      alpha agents in the treatment of giant cell arteritis. Finally, low-dose aspirin
      has been shown in a recent retrospective study to decrease the rate of cranial
      ischemic complications secondary to giant cell arteritis. It is conceivable that
      the definition of different patterns of inflammation in giant cell arteritis in
      the future might facilitate the design of differentiated therapeutic approaches.

PMID- 15857797
TI  - How to induce remission in primary systemic vasculitis.
AB  - Systemic vasculitis is treatable but not curable. Combination therapy with
      corticosteroids and immune suppressives induces remission in approximately 90% of
      cases, and therapeutic regimens have been standardised by randomised controlled
      trials. Patient subgrouping at presentation reflects prognosis and influences the
      design of induction regimens. Ongoing problems are therapeutic toxicity,
      especially in the elderly, the quality of remission obtained and the need for
      long-term therapy to prevent relapse. Cyclophosphamide remains the most effective
      immune suppressive, and more recent protocols have minimised its toxicity. An
      increasing range of newer immune suppressives, and therapeutic recombinant
      proteins aimed at cytokine blockade or lymphocyte depletion, is emerging. Their
      correct evaluation and integration with current regimens to improve long-term
      outcome is the major challenge in clinical vasculitis research today.

PMID- 15857798
TI  - How can relapses be detected and prevented in primary systemic small-vessel
      vasculitides?
AB  - Relapse is an important outcome measure in patients with Wegener's
      granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome. Although
      relapses are common in these diseases, it remains unclear why these occur and
      whether they are influenced by exogenous or endogenous factors. A key to
      minimizing the consequences of relapse is early recognition through monitoring.
      This is particularly essential to detect glomerulonephritis that is often
      asymptomatic and can be rapidly progressive. While the presence of relapse is
      currently based on objective evidence of active disease, investigations seek to
      identify factors that may distinguish patients at risk of relapse or markers that
      reliably predict the occurrence of relapse prior to organ injury. With the
      ability to successfully induce remission and the toxicities of available
      therapies, the relapse rate has become a critical issue in assessing the efficacy
      of new treatments. Recent clinical trials have sought to investigate safer
      therapeutic options that decrease disease relapse.

PMID- 15857799
TI  - How to diagnose and treat secondary forms of vasculitis.
AB  - Vasculitis is considered to be secondary when it arises either in the context of
      a pre-existing connective tissue disease, as a result of direct infection with a
      limited range of organisms, especially viruses, or when it arises in response to
      exposure to a number of medications. Rheumatoid vasculitis is probably the most
      widely recognised form of secondary vasculitis, and in this article we review the
      incidence, clinical features and management of this condition. Infections may
      either trigger or cause some types of vasculitis. Drug therapy is a common cause
      of limited forms of vasculitis and may enhance our understanding of the mechanism
      of these diseases. The premature development of atherosclerosis in patients with
      existing connective tissue diseases or indeed primary vasculitis has been
      recognised for some time, and the underlying mechanisms are currently being
      studied. An appreciation of the complex and varied pathophysiology of secondary
      vasculitis may further our understanding of primary vasculitis.

PMID- 15857800
TI  - How can patient care be improved beyond medical treatment?
AB  - The outcome of systemic necrotizing vasculitides, with treatment, has improved
      over the past few decades, with a 5 year survival rate that currently exceeds
      80%. It is now well established that therapy has to be adapted to aetiology,
      pathogenesis and disease severity, but complementary measures can also be
      beneficial, for example systematic prophylaxis against infections and/or
      adjusting drug doses to biological parameters and the patient's general
      condition, especially for the elderly and those in intensive care units. A
      multifaceted and point-by-point approach to patient care is needed to further
      improve quality of life whenever possible.

PMID- 15857801
TI  - Drug resistant Plasmodium falciparum in an area of seasonal transmission.
AB  - Eastern Sudan lies at the edge of the malaria endemicity stratum, where
      transmission intensity is low and seasonal. The main malaria parasite in the
      region, Plasmodium falciparum, survives the long dry and transmission-free season
      as asymptomatic sub-patent infections, and resurges following annual rains. The
      short-lived annual transmission in this area precipitates cyclical malaria
      epidemics among the semi-immune inhabitants who resort to excessive anti-malarial
      drugs usage at this time of the year. Chloroquine resistance (CQR) first emerged
      in this area in the mid 1980s; however, subsequent surveys demonstrated that the
      rate of parasitological failure to CQ remained stable over a period of 8 years
      (1986-1993). Nevertheless, the CQR level varied between years in association with
      the amount of annual rain. Detailed molecular surveys revealed significant
      temporal fluctuations in the frequency of resistant P. falciparum genotypes,
      increasing during the dry season but dwindling at the start of the next
      transmission season. The pattern of spread of drug resistance in the area is
      discussed in the context of parasite biology and malaria epidemiology of this
      region.

PMID- 15857802
TI  - Identification of the promoter of human transcription factor Sp3 and evidence of
      the role of factors Sp1 and Sp3 in the expression of Sp3 protein.
AB  - In a study of the role of transcription factor Sp1 in the formation of tumors by
      human fibrosarcoma cell lines that overexpress it [Cancer Res., 65 (2005) 1007],
      we found that expression of an Sp1-specific ribozyme, not only reduced the level
      of Sp1 protein, but also that of Sp3 protein, and that when the protein levels of
      these two transcription factors in the fibrosarcoma cell lines were reduced to
      near that found in normal human fibroblasts, the cell lines could no longer form
      tumors. An Sp1-specific ribozyme could reduce the level of expression of both Sp1
      protein and Sp3 protein if the promoter of the Sp1 gene and that of the Sp3 gene
      both have Sp1/Sp3 transcription factor binding sites and if such sites are
      critically responsible for the level of expression of both Sp1 and Sp3 protein in
      the cells. The Sp1 minimal promoter has been identified and it has two Sp1/Sp3
      sites [J. Biol. Chem. 276 (2001) 22126]. To characterize the Sp3 promoter, we
      isolated 2.1 kb of the 5'-flanking region of the Sp3 gene, which contains Sp1/Sp3
      binding sites, and using an expression reporter assay, showed that it has
      promoter activity. We then systematically reduced the size of the 5' flanking
      region, and determined that the nt-339 to nt-39 fragment, which contains an
      Sp1/Sp3 binding site at nt-181 and another at nt-168, retained the same promoter
      activity as the 2.1 kb region. Electrophoretic mobility shift assays indicated
      that both Sp3 protein and Sp1protein bind to these two sites. By mutating either
      or both of these binding sites, we showed using the reporter assay that each site
      is required for full promoter activity. We then designed an Sp3-specific
      ribozyme, expressed it in a human fibrosarcoma cell line in which Sp1 protein and
      Sp3 protein are expressed at high levels, and found that, indeed, the level of
      expression of both proteins was significantly reduced.

PMID- 15857803
TI  - Surfactant protein A limits Pneumocystis murina infection in immunosuppressed
      C3H/HeN mice and modulates host response during infection.
AB  - The development of Pneumocystis murina pneumonia and host response were
      characterized over time and at different levels of infection in corticosteroid
      immunosuppressed surfactant protein A (SP-A) knockout and wild-type (WT) mice.
      Infection increased over time in both strains of mice; however, significantly
      more cyst forms were detected in the knockout mice at intermediate and late
      stages of infection. In mice with heavy infections, TNF-alpha and IFN-gamma
      protein concentrations were significantly higher in pulmonary lavage fluid from
      knockout mice. There was a significant positive correlation between TNF-alpha and
      IFN-gamma concentrations and the level of infection in knockout mice, but not in
      WT mice. No significant differences were detected in IL-1 levels between the two
      strains of mice at any of the time points or at any level of infection. At
      heavier infection levels, significantly more MIP-2 protein was detected in the
      lungs of knockout mice, but a significant positive correlation between MIP-2
      concentrations and the infection level was detected in both groups of mice. At
      the intermediate stage of infection, a significantly higher percentage of
      neutrophils was detected in the lungs of knockout mice than in WT mice. There was
      no difference in SP-D levels between WT and KO mice with identical levels of
      infection. These data support a protective role for SP-A in host defense against
      Pneumocystis and suggest that the effects of SP-A on the host response vary based
      on the intensity of the infection.

PMID- 15857804
TI  - Expression of adhesion molecules in lungs of mice infected with Paracoccidioides
      brasiliensis conidia.
AB  - In infected tissues, leukocyte recruitment is mediated by interactions between
      adhesion molecules, expressed on activated vascular endothelial cells, and
      ligands present on circulating cells. We evaluated the inflammatory response and
      the expression of cellular adhesion molecules (ICAM-1, VCAM-1, CD18, LFA-1 and
      Mac-1) in lungs of BALB/c mice infected with Paracoccidioides brasiliensis
      conidia. When compared with uninfected animals, infected mice had a significant
      increase in the inflammatory response during the first 4 days, peaking 2-3 days
      post-challenge, 40.3% vs. 0.0% and 41.8% vs. 0.7%, respectively. This
      inflammatory infiltrate was composed mainly of neutrophils and macrophages with a
      few eosinophils and lymphocytes. An increase in the intensity of
      immunofluorescence (IF) for ICAM-1 was also observed during days 1-4. ICAM-1 was
      present in bronchiolar epithelium, type II pneumocytes, and macrophages, as well
      as on vascular endothelium. The control animals presented ICAM-1 constitutively.
      In infected mice, VCAM-1 was only observed on vascular endothelium during the
      first 2 days, with some macrophages expressing this molecule throughout the study
      periods. CD18 and Mac-1 but not LFA-1 were expressed with a high intensity on
      neutrophils and macrophages present in the inflammatory infiltrate. In addition,
      we observed a significant decrease in Colony forming units (CFUs) after the first
      2 days post-challenge. These findings suggest that during these early stages, up
      regulation of ICAM-1, VCAM-1, CD18 and Mac-1 expression occurs, participating in
      the inflammatory process and as such, in the pathogenesis of
      paracoccidioidomycosis (PCM).

PMID- 15857805
TI  - Limited in vivo reactivity of polyclonal effector cytotoxic T cells towards
      altered peptide ligands.
AB  - T cell responses are regulated by the affinity/avidity of the T cell receptor for
      the MHC/peptide complex, available costimulation and duration of antigenic
      stimulation. Altered peptide ligands (APLs) are usually recognized with a reduced
      affinity/avidity by the T cell receptor and are often able to only partially
      activate T cells in vitro or may even function as antagonists. Here we assessed
      the ability of APLs derived from peptide p33 of lymphocytic choriomeningitis
      virus (LCMV) to mediate lysis of target cells in vivo, confer anti-viral
      protection and cause auto-immune disease. In general, in vitro cross-reactivity
      between APLs was rather limited, and even strongly cross-reactive cytotoxic T
      lymphocytes were only able to mediate moderate anti-viral protection. Partial
      protection was observed for infection with LCMV or low doses of recombinant
      vaccinia virus, while no reduced viral titers could be seen upon infection with
      high dose of vaccinia virus. In a transgenic mouse model expressing LCMV
      glycoprotein in the islets of the pancreas, APLs induced a transient insulitis
      but failed to induce autoimmune diabetes. Thus, effector functions induced by
      even highly homologous APLs are rather limited in vivo.

PMID- 15857806
TI  - Human eosinophils selectively recognize and become activated by bacteria
      belonging to different taxonomic groups.
AB  - Eosinophils are predominantly found in tissues that have an interface with the
      external environment and its bacterial flora, such as the gastrointestinal and
      respiratory tracts. Although it is not the primary function of eosinophils to
      phagocytose and kill bacteria, we hypothesized that they might be able to
      recognize and become activated by microorganisms that enter the normally sterile
      tissues where they reside. The aim of this study was to evaluate whether human
      eosinophils get universally activated by bacteria or if they discriminate between
      bacteria derived from different phylogenetic groups. Eleven bacterial species
      representative of different taxonomic groups were examined. A hierarchy was seen
      among the bacterial species regarding their capacity to activate eosinophils.
      Furthermore, several eosinophilic activation patterns were evoked by the
      different bacterial species. The strongest eosinophil activator, Escherichia
      coli, elicited chemotaxis, degranulation and respiratory burst. Low numbers of
      bacteria caused the release of the granule proteins major basic protein and
      eosinophil peroxidase, whereas high numbers were required for the release of
      eosinophil cationic protein (ECP). Eosinophils did not seem to discriminate
      between gram-positive and gram-negative bacteria, unlike monocytes. However, the
      release of ECP was mainly seen after stimulation with gram-negative species.
      Blockade of the formyl peptide receptor partially inhibited bacterial activation
      of eosinophils, implicating its involvement in this activity. We propose that the
      presence of defined bacterial species in the normally sterile tissues inhabited
      by eosinophils may constitute danger signals to eosinophils. This may be of
      importance in the perpetuation of allergic inflammation.

PMID- 15857807
TI  - Early events in HSV keratitis--setting the stage for a blinding disease.
AB  - The last decade has seen herpes simplex virus (HSV)-induced stromal keratitis
      (SK) research shift from being a topic only of interest to vision researchers to
      one that fascinates the general field of inflammatory disease. Studies on
      experimental mouse lesions have uncovered several fundamental processes that
      explain lesion development. In this model, the chronic immuno-inflammatory
      lesions are mainly orchestrated by CD4+ T cells, but multiple early events occur
      that set the stage for the subsequent pathology. These include virus replication,
      the production of key cytokines and chemokines, neovascularization of the
      avascular cornea and the influx of certain inflammatory cell types. Many of these
      early events are subject to modulation, providing an approach to controlling this
      important cause of human blindness. We also comment on events ongoing during
      chronic SK, debating whether or not these represent virus-induced or autoimmune
      lesions.

PMID- 15857808
TI  - Continued ribavirin monotherapy following interferon-ribavirin combination
      therapy is not effective for chronic hepatitis C.

PMID- 15857809
TI  - Birth and death rate estimates of cats and dogs in U.S. households and related
      factors.
AB  - Studies report variable factors associated with dog and cat surpluses in the
      United States. Estimates of cat and dog birth and death rates help understand the
      problem. This study collected data through a commercial survey company,
      distributing questionnaires to 7,399 cat- and dog-owning households (HHs) in
      1996. The study used an unequal probability sampling plan and reported estimates
      of means and variances as weighted averages. The study used estimates of HHs and
      companion animals for national projections. More than 9 million owned cats and
      dogs died during 1996-yielding crude death rates of 8.3 cat deaths/100 cats in
      HHs and 7.9 dog deaths/100 dogs in HHs. The study reported twice as many kitten
      as puppy litters, with an average litter size of 5.73 and 7.57, respectively. The
      study reported data on planned versus unplanned litters, reasons caregivers did
      not spay females, disposition of litters, and sources of animals added to HHs.
      These first national estimates indicate the magnitude of, and reasons for,
      animals leaving HHs. The crude birth rate was estimated to be 11.2 kittens/100
      cats in HHs and 11.4 puppies/100 dogs in HHs.

PMID- 15857810
TI  - Visitor circulation and nonhuman animal welfare: an overlooked variable?
AB  - This article investigates visitor circulation and behaviors within a gallery of
      primate exhibits in relation to their possible implications for nonhuman animal
      welfare. When entering a primate house, the majority of visitors (84%) turned
      right, a pattern upheld throughout all times of the day. These findings
      demonstrate the existence of the "right-turn" principle, a concept previously
      identified and investigated in the museum setting. The existence of this
      circulation pattern in zoos has important implications for the practical
      management of animal welfare issues because unbalanced or large numbers of
      visitors at specific enclosures could present a stressful influence. The
      "direction bias" could not be attributed to demographic or behavioral traits,
      therefore suggesting that the principle, like similar findings from museum
      research, generalizes across visitor populations and, therefore, zoos. A visitor
      sample at another exhibit (located outside the exhibit gallery) did not display a
      direction bias, suggesting that the marked circulation pattern may be specific to
      exhibit galleries. The article discusses the significance and consequences of
      visitor circulation with respect to visitor management and animal welfare.

PMID- 15857811
TI  - The bond that never developed: adoption and relinquishment of dogs in a rescue
      shelter.
AB  - This study carried out a survey in an Italian shelter to analyze adoptions
      resulting in the rejection of the newly adopted dog. The results of this study
      show that the number of dogs adopted and returned was stable during the study,
      that more females than males were adopted, and that males were more likely to be
      returned. Almost all the dogs were returned because of behavioral problems, and
      most were more than 6 months of age. Some dogs were returned more than once, with
      20% of the people who adopted the same dog at different times reporting the same
      behavioral problem. Having a house with a yard, a garden, or a terrace appeared
      to be important for better management of the dog and influenced the length of
      adoption. Half of the adopters had previous experience as caregiver for a dog;
      compared to adopters who had no previous experience, however, they returned their
      companion animal after a shorter period and because of behavioral reasons.
      Understanding why adopters return their dogs to shelters is an important step
      toward attempting to minimize relinquishments and, thus, optimize adoptions.

PMID- 15857812
TI  - Short communication: rat's demand for group size.
AB  - Social isolation compromises the welfare of rats. However, it is not clear how
      many rats should be housed together under laboratory conditions. Pair housing,
      sometimes recommended over group housing, may help avoid aggression and disease
      transmission. Female rats, however, showed the highest average demand for a group
      size of 6 (versus 1, 2, 4, and 12) when stocking density was maintained at 20
      cm2/rat. This finding contributes to work suggesting that rats should be group
      housed. This article shows that further studies are required into the actual
      risks of disease and injury associated with group versus pair housing.

PMID- 15857813
TI  - Flaws in federal regulations pertaining to the welfare of primates kept in
      research institutions.

PMID- 15857814
TI  - The dog in wolf's clothing?

PMID- 15857815
TI  - A fresh look at the wolf-pack theory of companion-animal dog social behavior.
AB  - A popular perspective on the social behavior of dogs in multiple-dog households
      sees the dogs' behavior as reflecting the sociobiological laws of the rigidly
      structured dominance hierarchy that has been described for wolf packs. This view
      suggests that aggression problems among dogs are natural expressions of conflict
      that arise whenever dominance status is in contention. One recommended solution
      has been for the owner to endorse and enforce a particular dominance hierarchy
      because, on the wolf pack model, aggression is minimized when the structure of
      the hierarchy is clear, strong, and stable. This article questions the validity
      of this perspective on 2 principal grounds. First, because it does not seem to
      occur in the wild, this article suggests the strong dominance hierarchy that has
      been described for wolves may be a by-product of captivity. If true, it implies
      that social behavior--even in wolves--may be a product more of environmental
      circumstances and contingencies than an instinctive directive. Second, because
      feral dogs do not exhibit the classic wolf-pack structure, the validity of the
      canid, social dominance hierarchy again comes into question. This article
      suggests that behavioral learning theory offers another perspective regarding the
      behavior of dogs and wolves in the wild or in captivity and offers an effective
      intervention for aggression problems.

PMID- 15857816
TI  - The concept of dominance and the treatment of aggression in multidog homes: a
      comment on van Kerkhove's commentary.

PMID- 15857822
TI  - Introduction to the AJR Technology Forum: issues, controversies & utility of
      PET/CT imaging.

PMID- 15857823
TI  - The T-tubule membrane ATP-operated P2X4 receptor influences contractility of
      skeletal muscle.
AB  - Evidence indicates that extracellular ATP may have relevant functions in skeletal
      muscle, even though the physiological role and distribution of specific signaling
      pathway elements are not well known. The present work shows that P2X4 receptor,
      an extracellular ATP-regulated cell membrane channel permeable to Ca2+, is
      expressed in several tissues of the rat, including skeletal muscle. A specific
      antibody detected a protein band of approximately 60 kDa. Immunofluorescence
      demonstrated that P2X4 has an intracellular localization, and confocal analysis
      revealed that the receptor colocalizes with the T-tubule membrane DHP receptor.
      Considering that the natural agonist of P2X4 is ATP, we explored if changes of
      extracellular ATP levels could occur in contracting skeletal muscle to regulate
      the channel. In vitro experiments showed that substantial ATP is released and
      rapidly hydrolyzed after electrical stimulation of rat muscle fibers. Results
      show that the presence of ATP-degrading enzymes (hexokinase/apyrase), inhibitors
      of P2X receptors or Ca2+-free conditions, all abolished the progressive twitch
      tension potentiation produced in soleus muscle by low-frequency (0.05 Hz)
      stimulation. These data reveal that ATP-mediated Ca2+ entry, most likely through
      P2X4 receptor, may play an important role in modulating the contractility of
      skeletal muscle.

PMID- 15857825
TI  - Activating cystic fibrosis transmembrane conductance regulator channels with pore
      blocker analogs.
AB  - Cystic fibrosis (CF) is caused by mutations that disrupt the surface localization
      and/or gating of the CF transmembrane conductance regulator (CFTR) chloride
      channel. The most common CF mutant is deltaF508-CFTR, which inefficiently
      traffics to the surfaces of most cells. The deltaF508 mutation may also disrupt
      the opening of CFTR channels once they reach the cell surface, but the extent of
      this gating defect is unclear. Here, we describe potent activators of wild-type
      and deltaF508-CFTR channels that are structurally related to 5-nitro-2-(3
      phenylpropylamino)benzoate (NPPB), a negatively charged pore blocker that we show
      to have mixed agonistic activity (channel activation plus voltage-dependent pore
      block). These CFTR agonists include 1) an uncharged NPPB analog that stimulates
      channel opening at submicromolar concentrations without blocking the pore and 2)
      curcumin, a dietary compound recently reported to augment deltaF508-CFTR function
      in mice by an unknown mechanism. The uncharged NPPB analog enhanced the
      activities of wild-type and deltaF508-CFTR channels both in excised membrane
      patches and in intact epithelial monolayers. This compound increased the open
      probabilities of deltaF508-CFTR channels in excised membrane patches by 10-15
      fold under conditions in which wild-type channels were already maximally active.
      Our results support the emerging view that CFTR channel activity is substantially
      reduced by the deltaF508 mutation and that effective CF therapies may require the
      use of channel openers to activate mutant CFTR channels at the cell surface.

PMID- 15857824
TI  - A novel 43-kDa protein as a negative regulatory component of phenoloxidase
      induced melanin synthesis.
AB  - The melanization reaction induced by activated phenoloxidase in arthropods is
      important in the multiple host defense innate immune reactions, leading to the
      sequestration and killing of invading microorganisms. This reaction ought to be
      tightly controlled because excessive formation of quinones and systemic
      hypermelanization are deleterious to the hosts, suggesting that a negative
      regulator(s) of melanin synthesis may exist in hemolymph. Here, we report the
      purification and cloning of a cDNA of a novel 43-kDa protein, from the meal-worm
      Tenebrio molitor, which functions as a melanization-inhibiting protein (MIP). The
      deduced amino acid sequence of 352 residues has no homology to known sequences in
      protein data bases. When the concentration of the 43-kDa protein was examined by
      Western blot analysis in a melanin-induced hemolymph prepared by injection of
      Candida albicans into T. molitor larvae, the 43-kDa protein specifically
      decreased in the melanin-induced hemolymph compared with control hemolymph.
      Recombinant MIP expressed in a baculovirus system had an inhibitory effect on
      melanin synthesis in vitro. RNA interference using a synthetic 445-mer double
      stranded RNA of MIP injected into Tenebrio larvae showed that melanin synthesis
      was markedly induced. These results suggest that this 43-kDa MIP inhibits the
      formation of melanin and thus is a modulator of the melanization reaction to
      prevent the insect from excessive melanin synthesis in places where it should be
      inappropriate.

PMID- 15857826
TI  - Role of CREB1 and NF{kappa}B-p65 in the down-regulation of renin gene expression
      by tumor necrosis factor {alpha}.
AB  - Tumor necrosis factor-alpha (TNFalpha) is a potent inhibitor of renin gene
      expression in renal juxtaglomerular cells. We have found that TNFalpha suppresses
      renin transcription via transcription factor NFkappaB, which targets a cAMP
      responsive element (CRE) in the renin promoter. Here we aimed to further clarify
      the role of NFkappaB and the canonical CRE-binding proteins of the CRE-binding
      protein/activating transcription factor (CREB/ATF) family in the inhibition of
      renin gene expression by TNFalpha in the juxtaglomerular cell line As4.1.
      TNFalpha caused a moderate decrease in the binding of CREB1 to its cognate CRE
      DNA binding site. On the other hand, NFkappaB-p65 transcriptional activity was
      substantially reduced by TNFalpha, which targeted a trans-activation domain at
      the very C terminus of the p65 molecule. Our results suggest that TNFalpha
      inhibits renin gene expression by decreasing the transactivating capacity of
      NFkappaB-p65 and partially by attenuating CREB1 binding to CRE.

PMID- 15857827
TI  - A novel peroxisome proliferator-activated receptor gamma isoform with dominant
      negative activity generated by alternative splicing.
AB  - We examined the peroxisome proliferator-activated receptor gamma (PPARG) locus in
      an attempt to identify expressed sequence tags and/or conserved non-coding
      sequences in the intron sequences containing open reading frames and potentially
      able to encode new proteins. We identified a new PPARG transcript, defined
      gammaORF4, which harbors a readthrough in intron 4. The expected translated
      protein lacks the ligand-binding domain encoded by exons 5 and 6. We identified
      the transcript in human tumor cell lines and tissues, synthesized the cDNA, and
      cloned it in expression vectors. Using transient transfections, we found that
      gammaORF4 cDNA is translated into a predominantly nuclear protein that does not
      transactivate a reporter gene. Moreover, the isoform is dominant negative versus
      PPARgamma. Interestingly, gammaORF4 was expressed in vivo in a series of sporadic
      colorectal cancers. In some cases, it was expressed, albeit at lower levels, also
      in the mucosa adjacent to the tumors, suggesting that it may be related to
      tumorigenesis. A tumorigenic effect of gammaORF4 is in line with our finding that
      gammaORF4 has not only lost the capacity to restrain cell growth but has acquired
      the potential to stimulate it. In conclusion, this study demonstrates that
      gammaORF4 is expressed in vivo, that it has lost some PPARgamma properties, and
      that it affects PPARgamma functioning. The ability to counteract PPARgamma
      suggests that gammaORF4 plays a role in the pathogenesis of colorectal cancers.

PMID- 15857828
TI  - Somatostatin receptor type 5 modulates somatostatin receptor type 2 regulation of
      adrenocorticotropin secretion.
AB  - Somatostatin inhibits adrenocorticotropin (ACTH) secretion from pituitary tumor
      cells. To assess the contribution of somatostatin receptor subtype 5 (SST5) to
      somatostatin receptor subtype 2 (SST2) action in these cells, we assessed
      multipathway responses to novel highly monoreceptor-selective peptide agonists
      and multireceptor agonists, including octreotide and somatostatin-28. Octreotide
      and somatostatin-28 cell membrane binding affinities correlated with their
      respective SST2-selective peptide ligand. Although octreotide had similar
      inhibiting potency (picomolar) for cAMP accumulation and ACTH secretion as an
      SST2-selective agonist, somatostatin-28 exhibited a higher potency (femtomolar).
      Baseline spontaneous calcium oscillations assessed by fluorescent confocal
      microscopy revealed two distinct effects: SST2 activation reduced oscillations at
      femtomolar concentrations reflected by high inhibiting potency of averaged
      normalized oscillation amplitude, whereas SST5 activation induces brief
      oscillation pauses and increased oscillation amplitude. Octreotide exhibits an
      integrated effect of both receptors; however, somatostatin-28 exhibited a complex
      response with two separate inhibitory potencies. SST2 internalization was
      visualized with SST2-selective agonist at lower concentrations than for
      octreotide or somatostatin-28, whereas SST5 did not internalize. Using
      monoreceptor-selective peptide agonists, the results indicate that, in AtT-20
      cells, SST5 regulates the dominant SST2 action, attenuating SST2 effects on
      intracellular calcium oscillation and internalization. This may explain superior
      somatostatin-28 potency and provides a rationale for somatostatin ligand design
      to treat ACTH-secreting pituitary tumors.

PMID- 15857829
TI  - Structure of Escherichia coli UMP kinase differs from that of other nucleoside
      monophosphate kinases and sheds new light on enzyme regulation.
AB  - Bacterial UMP kinases are essential enzymes involved in the multistep synthesis
      of nucleoside triphosphates. They are hexamers regulated by the allosteric
      activator GTP and inhibited by UTP. We solved the crystal structure of
      Escherichia coli UMP kinase bound to the UMP substrate (2.3 A resolution), the
      UDP product (2.6 A), or UTP (2.45 A). The monomer fold, unrelated to that of
      other nucleoside monophosphate kinases, belongs to the carbamate kinase-like
      superfamily. However, the phosphate acceptor binding cleft and subunit assembly
      are characteristic of UMP kinase. Interactions with UMP explain the high
      specificity for this natural substrate. UTP, previously described as an
      allosteric inhibitor, was unexpectedly found in the phosphate acceptor site,
      suggesting that it acts as a competitive inhibitor. Site-directed mutagenesis of
      residues Thr-138 and Asn-140, involved in both uracil recognition and active site
      interaction within the hexamer, decreased the activation by GTP and inhibition by
      UTP. These experiments suggest a cross-talk mechanism between enzyme subunits
      involved in cooperative binding at the phosphate acceptor site and in allosteric
      regulation by GTP. As bacterial UMP kinases have no counterpart in eukaryotes,
      the information provided here could help the design of new antibiotics.

PMID- 15857830
TI  - Identification of an essential cleavage site in ColE7 required for import and
      killing of cells.
AB  - Colicin E7 (ColE7), a nuclease toxin released from Escherichia coli, kills
      susceptible bacteria under environmental stress. Nuclease colicins are processed
      during translocation with only the cytotoxic nuclease domains traversing the
      inner membrane to cleave tRNA, rRNA, or DNA in the cytoplasm of target cells. In
      this study, we show that the E. coli periplasmic extract cleaves ColE7 between
      Lys(446) and Arg(447) in the presence or absence of its inhibitor Im7 protein.
      Several residues near cleavage sites were mutated, but only mutants of Arg(447)
      completely lost in vivo cell-killing activity. Both the full-length and the
      nuclease domain of Arg(447) mutants retained their nuclease activities,
      indicating that failure to kill cells was not a consequence of damage to the
      endonuclease activity of the enzyme. Moreover, the R447E ColE7 mutant was not
      cleaved at its 447 site by periplasmic extracts or transported into the cytoplasm
      of target cells. Collectively, these results suggest that ColE7 is cleaved at
      Arg(447) during translocation and that cleavage is an essential step for ColE7
      import into the cytoplasm of target cells and its cell-killing activity.
      Conserved basic residues aligned with Arg(447) have also been found in other
      nuclease colicins, implying that the processing at this position may be common to
      other colicins during translocation.

PMID- 15857831
TI  - Solution structure of microtubule-associated protein light chain 3 and
      identification of its functional subdomains.
AB  - Microtubule-associated protein (MAP) light chain 3 (LC3) is a human homologue of
      yeast Apg8/Aut7/Cvt5 (Atg8), which is essential for autophagy. MAP-LC3 is cleaved
      by a cysteine protease to produce LC3-I, which is located in cytosolic fraction.
      LC3-I, in turn, is converted to LC3-II through the actions of E1- and E2-like
      enzymes. LC3-II is covalently attached to phosphatidylethanolamine on its C
      terminus, and it binds tightly to autophagosome membranes. We determined the
      solution structure of LC3-I and found that it is divided into N- and C-terminal
      subdomains. Additional analysis using a photochemically induced dynamic nuclear
      polarization technique also showed that the N-terminal subdomain of LC3-I makes
      contact with the surface of the C-terminal subdomain and that LC3-I adopts a
      single compact conformation in solution. Moreover, the addition of
      dodecylphosphocholine into the LC3-I solution induced chemical shift
      perturbations primarily in the C-terminal subdomain, which implies that the two
      subdomains have different sensitivities to dodecylphosphocholine micelles. On the
      other hand, deletion of the N-terminal subdomain abolished binding of tubulin and
      microtubules. Thus, we showed that two subdomains of the LC3-I structure have
      distinct functions, suggesting that MAP-LC3 can act as an adaptor protein between
      microtubules and autophagosomes.

PMID- 15857832
TI  - SUMO modification of the Ets-related transcription factor ERM inhibits its
      transcriptional activity.
AB  - A variety of transcription factors are post-translationally modified by SUMO, a
      97-residue ubiquitin-like protein bound covalently to the targeted lysine. Here
      we describe SUMO modification of the Ets family member ERM at positions 89, 263,
      293, and 350. To investigate how SUMO modification affects the function of ERM,
      Ets-responsive intercellular adhesion molecule 1 (ICAM-1) and E74 reporter
      plasmids were employed to demonstrate that SUMO modification causes inhibition of
      ERM-dependent transcription without affecting the subcellular localization,
      stability, or DNA-binding capacity of the protein. When the adenoviral protein
      Gam1 or the SUMO protease SENP1 was used to inhibit the SUMO modification
      pathway, ERM-dependent transcription was de-repressed. These results demonstrate
      that ERM is subject to SUMO modification and that this post-translational
      modification causes inhibition of transcription-enhancing activity.

PMID- 15857833
TI  - Acceleration of yeast actin polymerization by yeast Arp2/3 complex does not
      require an Arp2/3-activating protein.
AB  - The Arp2/3 complex creates filament branches leading to an enhancement in the
      rate of actin polymerization. Work with Arp complexes from different sources
      indicated that it was inactive by itself, required an activating factor such as
      the Wiskott-Aldrich syndrome protein (WASP), and might exhibit a preference for
      ATP or ADP-P(i) actin. However, with yeast actin, P(i) release is almost
      concurrent with polymerization, eliminating the presence of an ADP-P(i) cap. We
      thus investigated the ability of the yeast Arp2/3 complex (yArp2/3) to facilitate
      yeast actin polymerization in the presence and absence of the Arp2/3-activating
      factor Las17p WA. yArp2/3 significantly accelerates yeast actin but not muscle
      actin polymerization in the absence of Las17p WA. The addition of Las17p WA
      further enhances yeast actin polymerization by yArp2/3 and allows the complex to
      now assist muscle actin polymerization. This actin isoform difference is not
      observed with bovine Arp2/3 complex, because the neural WASP VCA fragment is
      required for polymerization of both actins. Observation of individual branching
      filaments showed that Las17p WA increased the persistence of filament branches.
      Compared with wild type actin, the V159N mutant actin, proposed to be more ATP
      like in behavior, exhibited an enhanced rate of polymerization in the presence of
      the yArp2/3 complex. yArp2/3 caused a significant rate of P(i) release prior to
      observation of an increase in filament mass but while branched structures were
      present. Thus, yeast F-actin can serve as a primary yArp2/3-activating factor,
      indicating that a newly formed yeast actin filament has a topology, unlike that
      of muscle actin, that is recognized specifically by yArp2/3.

PMID- 15857834
TI  - Regulation of E-cadherin endocytosis by nectin through afadin, Rap1, and p120ctn.
AB  - Adherens junctions (AJs) are a major cell-cell adhesion structure in epithelial
      cells that are formed by two major cell-cell adhesion molecules, E-cadherin and
      nectin. We have previously shown that nectin first forms cell-cell adhesion and
      then recruits non-trans-interacting E-cadherin to the nectin-based cell-cell
      adhesion sites, which gradually trans-interact there, eventually forming AJs. We
      have examined here the effect of trans-interacting nectin on non-trans
      interacting E-cadherin endocytosis. Trans-interacting nectin capable of
      associating with afadin, but not trans-interacting nectin mutant incapable of
      associating with afadin, inhibited non-trans-interacting E-cadherin endocytosis
      in intact cells. Afadin is a nectin- and actin filament-binding protein that
      connects nectin to the actin cytoskeleton. Studies on the mode of action of the
      nectin-afadin system using cell-free assay revealed that afadin associated with
      nectin bound Rap1 activated by trans-interacting nectin, interacted with p120ctn,
      and strengthened the binding of p120ctn to E-cadherin, eventually reducing non
      trans-interacting E-cadherin endocytosis. Afadin, which did not bind Rap1, was
      inactive in this capacity. These results indicate that trans-interacting nectin
      inhibits non-trans-interacting E-cadherin endocytosis through afadin, Rap1, and
      p120ctn and thereby further accumulates non-trans-interacting E-cadherin to the
      nectin-based cell-cell adhesion sites for the formation of AJs.

PMID- 15857835
TI  - Nuclear factor of activated T cells and serum response factor cooperatively
      regulate the activity of an alpha-actin intronic enhancer.
AB  - Expression of alpha-actin in smooth muscle cells (SMCs) is regulated, in part, by
      an intronic serum response factor (SRF)-binding CArG element. We have identified
      a conserved nuclear factor of activated T cells (NFAT) binding site that overlaps
      this CArG box and tested the hypothesis that this site plays a previously
      unrecognized role in regulating alpha-actin expression. A reporter construct
      prepared using a 56-bp region of the mouse alpha-actin first intron containing
      SRF, NFAT, and AP-1 sites (SNAP) acted as an enhancer element in the context of a
      minimal thymidine kinase promoter. Basal reporter activity following expression
      in SMCs was robust and sensitive to the calcineurin-NFAT pathway inhibitors
      cyclosporin A and FK506. Mutating either the NFAT or SRF binding site essentially
      abolished reporter activity, suggesting that both NFAT and SRF binding are
      required. Basal activity in non-smooth muscle HEK293 cells was SRF-dependent but
      NFAT-independent and approximately 8-fold lower than that in SMCs. Activation of
      NFAT in HEK293 cells induced an approximately 4-fold increase in activity that
      was dependent on the integrity of both NFAT and SRF binding sites. NFATc3.SRF
      complex formation, demonstrated by co-immunoprecipitation, was facilitated by the
      presence of SNAP oligonucleotide. Inhibition of the calcineurin-NFAT pathway
      decreased alpha-actin expression in cultured SMCs, suggesting that the molecular
      interaction of NFAT and SRF at SNAP may be physiologically relevant. These data
      provide the first evidence that NFAT and SRF may interact to cooperatively
      regulate SMC-specific gene expression and support a role for NFAT in the
      phenotypic maintenance of smooth muscle.

PMID- 15857836
TI  - Reduction of irreversible protein adsorption on solid surfaces by protein
      engineering for increased stability.
AB  - The influence of protein stability on the adsorption and desorption behavior to
      surfaces with fundamentally different properties (negatively charged, positively
      charged, hydrophilic, and hydrophobic) was examined by surface plasmon resonance
      measurements. Three engineered variants of human carbonic anhydrase II were used
      that have unchanged surface properties but large differences in stability. The
      orientation and conformational state of the adsorbed protein could be elucidated
      by taking all of the following properties of the protein variants into account:
      stability, unfolding, adsorption, and desorption behavior. Regardless of the
      nature of the surface, there were correlation between (i) the protein stability
      and kinetics of adsorption, with an increased amplitude of the first kinetic
      phase of adsorption with increasing stability; (ii) the protein stability and the
      extent of maximally adsorbed protein to the actual surface, with an increased
      amount of adsorbed protein with increasing stability; (iii) the protein stability
      and the amount of protein desorbed upon washing with buffer, with an increased
      elutability of the adsorbed protein with increased stability. All of the above
      correlations could be explained by the rate of denaturation and the
      conformational state of the adsorbed protein. In conclusion, protein engineering
      for increased stability can be used as a strategy to decrease irreversible
      adsorption on surfaces at a liquid-solid interface.

PMID- 15857837
TI  - Shotgun alanine scanning shows that growth hormone can bind productively to its
      receptor through a drastically minimized interface.
AB  - The high affinity binding site (Site1) of the human growth hormone (hGH) binds to
      its cognate receptor (hGHR) via a concave surface patch containing about 35
      residues. Using 167 sequences from a shotgun alanine scanning analysis of Site1,
      we have determined that over half of these residues can be simultaneously changed
      to an alanine or a non-isosteric amino acid while still retaining a high affinity
      interaction. Among these hGH variants the distribution of the mutation is highly
      variable throughout the interface, although helix 4 is more conserved than the
      other binding elements. Kinetic and thermodynamic analyses were performed on 11
      representative hGH Site1 variants that contained 14-20 mutations. Generally, the
      tightest binding variants showed similar associated rate constants (k(on)) as the
      wild-type (wt) hormone, indicating that their binding proceeds through a similar
      transition state intermediate. However, calorimetric analyses indicate very
      different thermodynamic partitioning: wt-hGH binding exhibits favorable enthalpy
      and entropy contributions, whereas the variants display highly favorable enthalpy
      and highly unfavorable entropy contributions. The heat capacities (DeltaCp) on
      binding measured for wt-hGH and its variants are significantly larger than
      normally seen for typical protein-protein interactions, suggesting large
      conformational or solvation effects. The multiple Site1 mutations are shown to
      indirectly affect binding of the second receptor at Site2 through an allosteric
      mechanism. We show that the stability of the ternary hormone-receptor complex
      reflects the affinity of the Site2 binding and is surprisingly exempt from
      changes in Site1 affinity, directly demonstrating that dissociation of the active
      signaling complex is a stepwise process.

PMID- 15857838
TI  - Isolation and characterization of a rice mutant hypersensitive to Al.
AB  - Rice (Oryza sativa L.) is a highly Al-resistant species among small grain crops,
      but the mechanism responsible for the high Al resistance has not been elucidated.
      In this study, rice mutants sensitive to Al were isolated from M(3) lines derived
      from an Al-resistant cultivar, Koshihikari, irradiated with gamma-rays. Relative
      root elongation was used as a parameter for evaluating Al resistance. After
      initial screening plus two rounds of confirmatory testing, a mutant (als1) was
      isolated from a total of 560 lines. This mutant showed a phenotype similar to the
      wild-type plant in the absence of Al. However, in the presence of 10 microM Al,
      root elongation was inhibited 70% in the mutant, but only 8% in the wild-type
      plant. The mutant also showed poorer root growth in acid soil. The Al content of
      root apices (0-1 cm) was much lower in the wild-type plant. The sensitivity to
      other metals including Cd and La did not differ between the mutant and the wild
      type plants. A small amount of citrate was secreted from the roots of the mutant
      in response to Al stress, but there was no difference from that secreted by the
      wild-type plant. Genetic analysis of F(2) populations between als1 and wild-type
      plants showed that the Al-resistant seedlings and Al-sensitive seedlings
      segregated at a 3 : 1 ratio, indicating that the high sensitivity to Al in als1
      is controlled by a single recessive gene. The gene was mapped to the long arm of
      chromosome 6, flanked by InDel markers MaOs0619 and MaOs0615.

PMID- 15857839
TI  - Ubiquitin folds through a highly polarized transition state.
AB  - The small alpha/beta protein ubiquitin has been used as a model system for
      experimental and computational studies on protein folding for many years. Here,
      we present a comprehensive phi-value analysis and characterize the structure and
      energetics of the transition state ensemble (TSE). Twenty-seven non-disruptive
      mutations are made throughout the structure and a range of phi-values from zero
      to one are observed. The values cluster such that medium and high values and
      found only in the N-terminal region of the protein, whilst the C-terminal region
      has consistently low phi-values. In the TSE, the main alpha-helix appears to be
      fully formed (two phi-values which specifically probe helical structure are one)
      and the helix is stabilized by packing against the first beta-turn, which is
      partially structured. In striking comparison, the phi-values in the C-terminal
      region are all very low, suggesting that this region of the protein is largely
      unstructured in the TSE. Data are consistent with a nucleation-condensation
      mechanism in which there is a highly polarized folding nucleus comprising the
      first beta-hairpin and the alpha-helix. Data presented from the protein
      engineering study and phi-value analysis are compared with results from other
      experimental studies and also computational studies.

PMID- 15857840
TI  - Mucinous histology predicts for reduced fluorouracil responsiveness and survival
      in advanced colorectal cancer.
AB  - BACKGROUND: Mucinous carcinoma of the colon and rectum (mucinous CRC) is a
      histological subtype of colorectal adenocarcinoma for which there is little data
      on chemotherapy responsiveness. The purpose of this study was to investigate
      specifically the efficacy of fluorouracil-based first-line chemotherapy in
      patients with advanced mucinous CRC. PATIENTS AND METHODS: All patients with
      advanced mucinous CRC enrolled in three prospective randomized trials evaluating
      infused 5-fluorouracil as first-line treatment were compared with patients with
      non-mucinous subtypes enrolled in the same trials in a case-control study.
      Prognostic factors associated with overall response rate (ORR), progression-free
      survival (PFS) and overall survival (OS) were identified using univariate and
      multivariate logistic and/or Cox proportional hazards analyses. RESULTS: The
      study included 135 patients (45 cases and 90 controls). The response rates for
      cases and controls were 22% [95% confidence interval (CI), 11% to 38%] and 47%
      (95% CI, 36.1% to 58.2%), respectively (P=0.0058). Median OS for the mucinous CRC
      patients was 11.8 months (95% CI, 8.87-14.8) compared with 17.9 months (95% CI,
      13.38-22.39) in the control group (univariate analysis, P=0.056); after
      correcting for significant prognostic factors by multivariate Cox regression
      analysis, P=0.0372 and hazard ratio (HR)=1.497 (1.02-2.19). CONCLUSION: Patients
      with advanced mucinous CRC have a poorer response to fluorouracil-based first
      line chemotherapy and reduced survival compared with patients with non-mucinous
      CRC.

PMID- 15857841
TI  - Vinorelbine and prednisone in frail elderly patients with intermediate-high grade
      non-Hodgkin's lymphomas.
AB  - BACKGROUND: Frail patients with non-Hodgkin's lymphoma (NHL) are generally
      excluded from clinical trials and not even treated. The aim of this study was to
      evaluate the efficacy and tolerability of vinorelbine and prednisone in frail
      elderly patients with NHL. PATIENTS AND METHODS: Thirty consecutive frail elderly
      patients were entered in a phase II study with vinorelbine 25 mg/m2 i.v. on days
      1 and 8 and oral prednisone 30 mg total dose on days 1-8 for six cycles. Criteria
      of frailty were age > or =80 years, or age > or =70 years and three or more
      comorbidities of grade 3 or at least one comorbidity of grade 4 according to the
      Cumulative Illness Rating Scale (CIRS), or not self-sufficient or the presence of
      one or more geriatric syndromes. RESULTS: Of 30 evaluable patients, three (10.0%)
      achieved a complete response (CR), nine (30.0%) showed a partial response (PR),
      while 10 presented with stable disease and eight with progressive disease. The
      median duration of CR was 29 months (range 5-36 months), and the median duration
      of PR was 1 month (range 1-22 months). Three patients had grade 3 neutropenia and
      one had grade 4. One grade 4 neurotoxicity was observed. Three patients died
      because of heart failure within 28 days of therapy, and one patient died after 4
      days because of rapid progression. The median overall survival was only 10
      months. CONCLUSION: Vinorelbine and prednisone is a relatively non-toxic
      combination with modest activity in frail patients with NHL. If initial
      aggressive chemotherapy has been excluded, this combination could be tried to
      obtain a temporary palliation.

PMID- 15857842
TI  - Little response to zoledronic acid in a child of juvenile myelomonocytic leukemia
      (JMML) harboring the PTPN11 mutation.

PMID- 15857843
TI  - Severe interstitial pneumonitis following rituximab and bleomycin-containing
      combination chemotherapy.

PMID- 15857844
TI  - Temozolomide in combination with BCNU before and after radiotherapy in patients
      with inoperable newly diagnosed glioblastoma multiforme.
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy and safety of
      carmustine (BCNU) in combination with temozolomide as first-line chemotherapy
      before and after radiotherapy (RT) in patients with inoperable, newly diagnosed
      glioblastoma multiforme (GBM). PATIENTS AND METHODS: Forty patients were treated
      with BCNU (150 mg/m2) on day 1 and temozolomide (110 mg/m2/day) on days 1 through
      5 of each 42-day cycle for up to four cycles prior to conventional RT (2 Gy
      fractions to a total of 60 Gy). After RT, BCNU + temozolomide was administered
      for four additional cycles or until progression. The primary end point was
      response rate; secondary end points included progression-free survival (PFS);
      overall survival (OS) and safety. RESULTS: Sixty per cent of patients completed
      four cycles of neo-adjuvant BCNU + temozolomide. Objective response rate
      (intention-to-treat) was 42.5% (95% confidence interval 27% to 58%), including
      two (5%) complete and 15 (37.5%) partial responses. In the eligible population
      (n=37) the objective response rate was 46%. Nine (24%) patients had stable
      disease and 14 (35%) had progressive disease. Median PFS and OS were 7.4 and 12.7
      months, respectively. Age was the only significant prognostic factor and tumor
      location (lobar versus multifocal versus corpus callosum) showed a trend. Grade 3
      4 toxicities included thrombocytopenia (n=11) and neutropenia (n=7) for both pre-
      and post-RT chemotherapy. Four patients required platelet transfusions. No
      patient discontinued treatment because of toxicity. CONCLUSIONS: The combination
      of BCNU plus temozolomide as neo-adjuvant therapy in inoperable GBM exhibited
      promising activity with a good safety profile and warrants further evaluation.

PMID- 15857845
TI  - Release of doxorubicin in sweat: first step to induce the palmar-plantar
      erythrodysesthesia syndrome?

PMID- 15857846
TI  - Is cardiac troponin T serum level an accurate surrogate for acute doxorubicin
      related myocardial injury?

PMID- 15857847
TI  - Does the concurrent use of anthracycline and granulocyte colony-stimulating
      factor influence the risk of secondary leukaemia in breast cancer women?

PMID- 15857848
TI  - Predictors of prescription of morphine for severe cancer pain by physicians in
      Korea.
AB  - BACKGROUND: This study was undertaken to identify predictors of the prescription
      of strong opioids, which are important for the management of severe cancer pain,
      by Korean physicians. METHODS: A questionnaire based on a hypothetical case
      designed to assess the prescription of morphine by physicians was administered to
      800 specialists in the Korea Cancer Association, of whom 147 (18.4%) responded,
      and to 2200 specialists in the Korean Academy of Family Medicine, of whom 388
      (17.6%) responded. We used a multidimensional approach to identify the predictors
      of prescription of morphine by physicians. RESULTS: In the hypothetical case
      scenario, only 16.5% of the respondents stated that they would prescribe morphine
      for severe cancer pain. Multiple logistic regression analysis showed that
      physicians with a positive attitude regarding opioid addiction [odds ratio (OR)
      2.62; 95% confidence interval (CI) 1.54-4.46], experience of pain assessment (OR
      2.09; 95% CI 1.13-3.87), recent residency training (OR 2.27; 95% CI 1.30-4.0) and
      positive self-evaluation as an oncology specialist (OR 2.60; 95% CI 1.41-4.78)
      were more likely to prescribe morphine. None of the 13 variables in the knowledge
      dimension significantly predicted prescription of morphine for severe cancer
      pain. CONCLUSIONS: The results of the survey suggest that we need to develop
      strategies to develop a positive attitude toward opioids, to increase experience
      in pain assessment and to improve cancer pain management training among Korean
      physicians.

PMID- 15857849
TI  - Hardening by partial dehydration and ABA increase desiccation tolerance in the
      cyanobacterial lichen Peltigera polydactylon.
AB  - BACKGROUND AND AIMS: The ability of partial dehydration and abscisic acid
      pretreatments to increase desiccation tolerance in the cyanobacterial lichen
      Peltigera polydactylon was tested. * METHODS: Net photosynthesis and respiration
      were measured using infrared gas analysis during a drying and rehydration cycle.
      At the same time, the efficiency of photosystem two was measured using
      chlorophyll fluorescence, and the concentrations of chlorophyll a were
      spectrophotometrically assayed. Heat production was also measured during a
      shorter drying and rehydration cycle using differential dark microcalorimetry. *
      KEY RESULTS: Pretreating lichens by dehydrating them to a relative water content
      of approx. 0.65 for 3 d, followed by storing thalli hydrated for 1 d in the
      light, significantly improved their ability to recover net photosynthesis during
      rehydration after desiccation for 15 but not 30 d. Abscisic acid pretreatment
      could substitute for partial dehydration. The improved rates of photosynthesis
      during the rehydration of pretreated material were not accompanied by
      preservation of photosystem two activity or chlorophyll a concentrations compared
      with untreated lichens. Partial dehydration and ABA pretreatments appeared to
      have little direct effect on the desiccation tolerance of the mycobiont, because
      the bursts of respiration and heat production that occurred during rehydration
      were similar in control and pretreated lichens. * CONCLUSIONS: Results indicate
      that the photobiont of P. polydactylon possesses inducible tolerance mechanisms
      that reduce desiccation-induced damage to carbon fixation, and will therefore
      improve the supply of carbohydrates to the whole thallus following stress. In
      this lichen, ABA is involved in signal transduction pathways that increase
      tolerance of the photobiont.

PMID- 15857850
TI  - Wind-dispersed seed deposition patterns and seedling recruitment of Artemisia
      halodendron in a moving sandy land.
AB  - BACKGROUND AND AIMS: Artemisia halodendron is a native sub-shrub that occurs
      mainly in moving and semi-fixed sandy lands in Inner Mongolia, China. Information
      on the spatial patterns of wind-dispersed seed deposition and seedling
      recruitment of A. halodendron inhabiting moving sandy lands is very limited. The
      aim of this study was to examine wind-dispersed seed deposition patterns and post
      dispersal recruitment of A. halodendron seedlings. * METHODS: The spatial
      patterns of wind-dispersed seed deposition and seedling recruitment of A.
      halodendron were examined by investigating the numbers of deposited seeds,
      emerged and surviving seedlings using sampling points at a range of distances
      from the parent plant in eight compass directions for two consecutive growing
      seasons. * KEY RESULTS: Wind-dispersed seed deposition showed considerable
      variation between directions and years. Wind transported A. halodendron seeds
      only a few meters away from the parent plant in all eight directions. Seedling
      emergence and establishment also showed between-direction and between-year
      variability, but the spatial pattern of seedling distribution differed from that
      of seed deposition. Only a very small fraction (<1 %) of the deposited seeds
      emerged in the field and survived for long enough to be included in our seedling
      censuses at the end of the growing season. * CONCLUSIONS: The spatial variation
      in wind speed and frequency strongly affects the pattern of seed deposition,
      although the variation in seed deposition does not determine the spatial pattern
      of seedling recruitment. Seeds of A. halodendron are not dispersed very well by
      wind. The low probability of recruitment success for A. halodendron seedlings
      suggests that this species does not rely on seedling recruitment for its
      persistence and maintenance of population.

PMID- 15857852
TI  - In vitro and in vivo suppression of GJB2 expression by RNA interference.
AB  - Mutations in GJB2 (gap junction protein, beta-2) are the major cause of autosomal
      recessive non-syndromic hearing loss. A few allele variants of this gene also
      cause autosomal dominant non-syndromic hearing loss as a dominant-negative
      consequence of expression of the mutant protein. Allele-specific gene suppression
      by RNA interference (RNAi) is a potentially attractive strategy to prevent
      hearing loss caused by this mechanism. In this proof-of-principle study, we
      identified a potent GJB2-targeting short interfering RNA (siRNA) to post
      transcriptionally silence the expression of the R75W allele variant of GJB2 in
      cultured mammalian cells. In a mouse model, this siRNA duplex selectively
      suppressed GJB2(R75W) expression by >70% of control levels, thereby preventing
      hearing loss. The level of endogenous murine Gjb2 expression was not affected.
      Our data show that RNAi can be used with specificity and efficiency in vivo to
      protect against hearing loss caused as a dominant-negative consequence of mutant
      gene expression.

PMID- 15857851
TI  - Early eptifibatide improves TIMI 3 patency before primary percutaneous coronary
      intervention for acute ST elevation myocardial infarction: results of the
      randomized integrilin in acute myocardial infarction (INTAMI) pilot trial.
AB  - AIMS: Adjunctive therapy with glycoprotein IIb/IIIa inhibitors has been shown to
      reduce ischaemic complications and improve clinical outcome in patients with
      primary percutaneous coronary intervention (PCI) for acute ST elevation
      myocardial infarction. Little is known about the use of eptifibatide in this
      setting. METHODS AND RESULTS: One hundred and two patients with ST elevation
      myocardial infarction <12 h scheduled for primary percutaneous intervention were
      randomly assigned to early eptifibatide given in the emergency room (early) or
      optional eptifibatide at the time of PCI (late or no). Primary endpoint was the
      patency of the infarct vessel before PCI. Patients in the early group received
      their first eptifibatide bolus, a mean of 45 min before angiography. TIMI 3
      patency before PCI was observed in 34% in the early group and 10% in late or no
      group (P=0.01). The incidence of complete ST resolution 1 h after PCI was 61% in
      early group and 66% in the late or no group, respectively (P=n.s.). There were no
      significant differences in the rates of TIMI 3 flow after PCI, death,
      reinfarction, stroke, and major bleeding complications until day 30. CONCLUSION:
      In this pilot trial, double bolus eptifibatide given in the emergency room
      improved TIMI 3 grade flow of the infarct-related coronary artery before PCI.
      These results should be confirmed in a larger trial and whether this advantage
      translates into an improvement in clinical outcome should be tested in a trial
      with primary clinical endpoints.

PMID- 15857853
TI  - CADASIL mutations impair Notch3 glycosylation by Fringe.
AB  - Mutations in the NOTCH3 gene trigger adult-onset stroke and vascular dementia in
      patients with CADASIL (cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy). All CADASIL mutations described to date affect
      the epidermal growth factor-like (EGF-like) repeats located in the extracellular
      domain of the Notch3 receptor. These domains are also the target of sequential
      complex O-linked glycosylation mediated by protein O-fucosyltransferase 1 and
      Fringe. We investigated whether O-fucosylation or Fringe-mediated elongation of O
      fucose on Notch3 is impaired by CADASIL mutations. Biochemical studies of a
      Notch3 fragment containing the first five EGF-like repeats of Notch3, including
      the mutational hot spot, showed that CADASIL mutations do not affect the addition
      of O-fucose but do impair carbohydrate chain elongation by Fringe. CADASIL
      changes also induced aberrant homodimerization of mutant Notch3 fragments and
      heterodimerization of mutant Notch3 with Lunatic Fringe itself. Together, these
      data suggest that Fringe plays a role in CADASIL pathophysiology.

PMID- 15857854
TI  - Global gene expression as a function of germline genetic variation.
AB  - Common, functional, germline genetic polymorphisms have been associated with
      clinical cancer outcomes. Little attention has been paid to the potential
      phenotypic consequences of germline genetic variation on downstream genes. We
      determined the germline status of 16 well-characterized functional polymorphisms
      in 126 children with newly diagnosed acute lymphoblastic leukemia (ALL). We
      assessed whether global gene expression profiles of diagnostic ALL blasts from
      the same patients differed by these germline polymorphic genotypes. Gene
      expression values were adjusted for ALL-subtype-specific patterns. Of the 16
      loci, only the UGT1A1 promoter repeat polymorphism [A(TA)nTAA] (UGT1A1*28) and
      GSTM1 deletion were significant predictors of global gene expression in a
      supervised approach, which divided patients based on their germline genotypes
      [UGT1A1: 124 probe sets, false discovery rate (FDR)=13%, P< or =0.0031; GSTM1:
      112 probe sets, FDR=42.5%, P< or =0.0084]. Genes whose expression distinguished
      the UGT1A1 (TA) 7/7 genotype from the other UGT1A1 genotypes included HDAC1, RELA
      and SLC2A1; those that distinguished the GSTM1 null genotype from non-null
      genotype included NBS1 and PRKR. In an unsupervised approach, the gene expression
      profiles using the entire array delineated two major clusters of patients. The
      only germline genotype frequency that differed between the two clusters was
      UGT1A1 (P=0.002; Fisher's exact test). Although their expression is limited to
      specific tissues, both GSTM1 and UGT1A1 are involved in the conjugation (and thus
      transport, excretion and lipophilicity) of a broad range of endobiotics and
      xenobiotics, which could plausibly have consequences for gene expression in
      different tissues.

PMID- 15857855
TI  - ADPEAF mutations reduce levels of secreted LGI1, a putative tumor suppressor
      protein linked to epilepsy.
AB  - Mutations in LGI1 have been linked to autosomal dominant partial epilepsy with
      auditory features (ADPEAF), an unusual inherited human partial epilepsy
      phenotype. In addition, decreases in LGI1 expression are observed in glioblastoma
      patient samples and glioblastoma cell lines. LGI1, one member of the LGI gene
      family, encodes a approximately 63 kDa protein, with strong regional expression
      in neurons within the temporal lobe. Although the function of LGI proteins
      remains unknown, structural analyses suggest that LGI1 could be either localized
      to the membrane or secreted. Here, we show that LGI1-4 exhibit overlapping
      patterns of diffuse mRNA expression in the adult mouse brain, with some areas of
      specific localization characteristic of each family member. We find robust
      secretion of mouse LGI1 protein following transfection into 293T cells. LGI
      family members, LGI3, LGI4 and a newly identified splice form of LGI2, LGI2B, are
      also secreted in culture, indicating that secretion is a conserved feature of
      this protein family. Introduction of mutations in LGI1, including those
      identified in ADPEAF pedigrees, reveals that the mutant proteins either are not
      secreted or are unstable. These results demonstrate loss-of-function as a
      pathogenic basis for LGI1-mediated ADPEAF.

PMID- 15857856
TI  - Human-mouse comparative analysis reveals that branch-site plasticity contributes
      to splicing regulation.
AB  - The formation of base-pairing between the branch-site (BS) sequence and the U2
      snRNP is an important step in mRNA splicing. We developed a new algorithm to
      identify both the BS sequence and the polypyrimidine tract (PPT) and validated
      its predictions experimentally. To assess BS conservation between human and
      mouse, we assembled and analyzed 46 812 and 242 constitutively and alternatively
      spliced orthologs of human-mouse intron pairs, respectively. Combinations of BSs
      and PPTs can be found in most of the constitutive and alternative introns. The
      average distance between the BS and the 3' splice site (3'ss) is 33-34 nt.
      Acceptor-like AG dinucleotides that resided between the predicted BS and the 3'ss
      were found to appear mostly within 5 nt, but not more than 19 nt, downstream of
      the BS. However, although 32% of homologous alternatively spliced BS sequences
      were fully conserved between human and mouse, only a small fraction (3%) of
      homologous constitutive counterparts was fully conserved. This indicates that the
      full sequence of the BS is under weak purifying selection in constitutively
      spliced introns and further strengthens the view that the BS sequence is just one
      of several factors determining the ability of the splicing machinery to identify
      the BS location. Mutations in the putative BS revealed a shift from constitutive
      to alternative splicing, and it also controls the inclusion/skipping ratio in
      alternative splicing. This suggests a role for BS sequences in regulated
      splicing.

PMID- 15857857
TI  - Longitudinal study of birth weight and adult body mass index in predicting risk
      of coronary heart disease and stroke in women.
AB  - OBJECTIVES: To determine whether birth weight and adult body size interact to
      predict coronary heart disease in women, as has been observed for men. To
      determine whether birth weight and adult body size interact to predict risk of
      stroke. DESIGN: Longitudinal cohort study. SETTING AND PARTICIPANTS: 66,111
      female nurses followed since 1976 who were born of singleton, term pregnancies
      and reported their birth weight in 1992. MAIN OUTCOME MEASURES: 1504 events of
      coronary heart disease (myocardial infarction or sudden cardiac death) and 1164
      strokes. RESULTS: For each kilogram of higher birth weight, age adjusted hazard
      ratios from prospective analysis were 0.77 (95% confidence interval 0.69 to 0.87)
      for coronary heart disease and 0.89 (0.78 to 1.01) for total stroke. In combined
      prospective and retrospective analysis, hazard ratios were 0.84 (0.76 to 0.93)
      for total stroke, 0.83 (0.71 to 0.96) for ischaemic stroke, and 0.86 (0.66 to
      1.11) for haemorrhagic stroke. Exclusion of macrosomic infants (> 4536 g) yielded
      stronger estimates. Risk of coronary heart disease was especially high for women
      who crossed from a low centile of weight at birth to a high centile of body mass
      index in adulthood. The association of lower birth weight with increased risk of
      stroke was apparent across categories of body mass index in adults and was not
      especially strong among heavier women. CONCLUSIONS: Higher body mass index in
      adulthood is an especially strong risk factor for coronary heart disease among
      women who were small at birth. In this large cohort of women, size at birth and
      adiposity in adulthood interacted to predict events of coronary heart disease but
      not stroke events.

PMID- 15857858
TI  - Factors associated with functioning style and coping strategies of families with
      a child with an autism spectrum disorder.
AB  - A survey of parents/caregivers of a child with an autism spectrum disorder (ASD)
      was conducted to examine the relationship between ASD characteristics, family
      functioning and coping strategies. Having a child with ASD places considerable
      stress on the family. Primary caregivers of a child with ASD from a regional and
      rural area in Victoria, Australia (N = 53) were surveyed concerning their child
      with ASD, family functioning (adaptability and cohesion), marital satisfaction,
      self-esteem and coping strategies. Results suggest that these caregivers had
      healthy self-esteem, although they reported somewhat lower marital happiness,
      family cohesion and family adaptability than did norm groups. Coping strategies
      were not significant predictors of these outcome variables. Results highlight the
      need for support programmes to target family and relationship variables as well
      as ASD children and their behaviours, in order to sustain the family unit and
      improve quality of life for parents and caregivers as well as those children.

PMID- 15857859
TI  - Attention, monotropism and the diagnostic criteria for autism.
AB  - The authors conclude from a range of literature relevant to the autistic
      condition that atypical strategies for the allocation of attention are central to
      the condition. This assertion is examined in the context of recent research, the
      diagnostic criteria for autism in DSM-IV and ICD-10, and the personal experiences
      of individuals with autism including one of the authors of the article. The first
      two diagnostic criteria are shown to follow from the 'restricted range of
      interests' referred to in the third criterion. Implications for practice are
      indicated.

PMID- 15857860
TI  - Social communication in children with autism: the relationship between theory of
      mind and discourse development.
AB  - This longitudinal study investigated the developmental trajectory of discourse
      skills and theory of mind in 57 children with autism. Children were tested at two
      time points spaced 1 year apart. Each year they provided a natural language
      sample while interacting with one parent, and were given standardized vocabulary
      measures and a developmentally sequenced battery of theory of mind tasks. The
      language samples were coded for conversational skills, specifically the child's
      use of topic-related contingent utterances. Children with autism made significant
      gains over 1 year in the ability to maintain a topic of discourse. Hierarchical
      regression analyses demonstrated that theory of mind skills contributed unique
      variance to individual differences in contingent discourse ability and vice
      versa, when measured concurrently; however, they did not predict longitudinal
      changes. The findings offer some empirical support for the hypothesis that theory
      of mind is linked to communicative competence in children with autism.

PMID- 15857861
TI  - The relationship between expressive language level and psychological development
      in children with autism 5 years of age.
AB  - The age of detection of autism varies and may be linked to differences in the
      severity of disturbance and any associated retardation. Symptom intensity,
      overall language level, age of recognition of first disturbances and level of
      psychological development were examined in 222 children with pervasive
      developmental disorder with a mean age of 5 years. Results showed a positive
      correlation between language level and psychological development as well as
      between language level and intensity of symptoms. The central position of
      language in psychological development is discussed.

PMID- 15857862
TI  - Adjustment in mothers of children with Asperger syndrome: an application of the
      double ABCX model of family adjustment.
AB  - The present study examined the applicability of the double ABCX model of family
      adjustment in explaining maternal adjustment to caring for a child diagnosed with
      Asperger syndrome. Forty-seven mothers completed questionnaires at a university
      clinic while their children were participating in an anxiety intervention. The
      children were aged between 10 and 12 years. Results of correlations showed that
      each of the model components was related to one or more domains of maternal
      adjustment in the direction predicted, with the exception of problem-focused
      coping. Hierarchical regression analyses demonstrated that, after controlling for
      the effects of relevant demographics, stressor severity, pile-up of demands and
      coping were related to adjustment. Findings indicate the utility of the double
      ABCX model in guiding research into parental adjustment when caring for a child
      with Asperger syndrome. Limitations of the study and clinical implications are
      discussed.

PMID- 15857863
TI  - Letter to the editors.

PMID- 15857864
TI  - The interaction between young people with atypical gender identity organization
      and their peers.
AB  - This exploratory study involved the qualitative analysis of the responses of
      eight children with atypical gender identity organization to open-ended questions
      about their experiences of secondary school. The aim was to develop an
      understanding of these young people's interaction with their peers. It became
      apparent that all but one of the participants had been bullied. In this context,
      participants reported difficulties in developing friendships, although each
      participant received support from at least one of their peers. Given the hostile
      school environment participants did not necessarily talk to these individuals
      about their experiences in relation to their gender identity. The clinical
      implications for working with young people on a developing gender identity, and
      the impact on their mental health, are considered.

PMID- 15857865
TI  - A social semiotic interpretation of suicidal behaviour in young people.
AB  - This article presents a study of nurses' and doctors' perceptions of young people
      who engage in suicidal behaviour. A contemporary view of grounded theory is used
      to guide the collection and analysis of qualitative data from nurses and doctors
      working with young people in an accident and emergency department, paediatric
      medicine and child and adolescent mental health services (adolescent inpatient
      unit). The analysis of 45 semi-structured interviews generated the category:
      Processes of communication and associated meanings: Another voice, Complex
      messages and Seeing and using the social environment. A social semiotic framework
      is used to explore the way in which nurses and doctors perceive young people who
      engage in suicidal behaviour. The article concludes by considering the
      implications for policy and practice.

PMID- 15857866
TI  - Sun protection as a family health project in families with adolescents.
AB  - This study examined sun protection in families with adolescents from an action
      theoretical perspective. Interview data were collected from 20 families about
      their attitudes and behaviors around sunbathing and sun protection. The data
      support the understanding of project as joint goal-directed action over time as
      the basis on which these behaviors are organized in families. Families used the
      language of goal-directed action to discuss family sun protection. Differences
      between families with focused and diffuse sun-protection projects are identified.
      Sun protection in families as one part of an array of family goal-directed
      actions and projects has implications for health promotion.

PMID- 15857867
TI  - The physical, emotional and interpersonal impact of HAART: exploring the
      realities of HIV seropositive individuals on combination therapy.
AB  - The purpose of this qualitative study was to understand the impact of HAART on
      the lives of HIV seropositive men and women. The data demonstrate that the
      demands of these treatments are substantial, but that renewed health and hope for
      the future due to the implementation of HAART often overshadows the stress of the
      treatments on the physical, emotional and social well-being of the individuals.
      Practitioners should be keenly aware of the struggles faced by those on HAART,
      and provide multidimensional support to assure maximum effectiveness of these
      treatments in light of the realities of their clients' lives.

PMID- 15857868
TI  - A stage model of blood donor behaviour: assessing volunteer behaviour.
AB  - Are there valid stages to explain blood donor behaviour? Three studies (event
      contingent diary, interview and psychometric) are reported that address this
      question. Stage and process constructs from the transtheoretical model (TTM),
      past behaviour and intentions are measured. The qualitative studies demonstrated
      that blood donors describe their behaviour using TTM constructs. The psychometric
      study identified: (1) groupings of blood donors consistent with Ferguson's (1996)
      stage predictions; (2) TTM constructs varied meaningfully as a function of these
      groupings; (3) associations within clusters indicated qualitatively distinct
      stages; and (4) TTM constructs showed incremental validity over intentions with
      respect to past behaviour.

PMID- 15857869
TI  - Motives for the adoption of protective health behaviours for men and women: an
      evaluation of the psychosocial-appraisal health model.
AB  - The present study has been designed to: (1) evaluate the adequacy of a
      psychosocial-appraisal health model posited to explain the decision-making
      processes associated with the intention as well as the (non)practice of
      protective behaviours; and (2) test for sex differences in the hypothesized
      structural relations (both direct and indirect) between the model's exogenous
      (psychosocial) and endogenous (cognitive appraisal) factors in representing the
      way health decisions are made. Results obtained from path analysis (N=1269)
      provided overall support for the 'fit' of the hypothesized health model. The
      implications of the findings with regard to differences in male and female health
      status are discussed.

PMID- 15857870
TI  - A qualitative analysis of psychological processes mediating quality of life
      impairments in chronic daily headache.
AB  - Quality of life impairments are greater in chronic daily headache (CDH) than in
      episodic headache conditions like migraine. This qualitative interview study
      aimed to identify psychological processes associated with quality of life
      impairments among individuals meeting diagnostic criteria for CDH. Grounded
      theory analysis showed that perceived loss of control was the central experience
      mediating the impact of CDH on quality of life. The results provide explanations
      for previous quantitative findings about quality of life impairments in CDH, and
      could inform interventions to reduce the impact of CDH. Further research could
      also examine the roles played by perceived control in the onset and development
      of CDH, including possible links with pre-emptive analgesic use.

PMID- 15857871
TI  - Understanding why people with type 1 diabetes do not attend for specialist
      advice: a qualitative analysis of the views of people with insulin-dependent
      diabetes who do not attend diabetes clinic.
AB  - Attendance at diabetes clinic is associated with improved medical outcome,
      however, significant numbers of people with type 1 diabetes choose not to attend.
      In order to understand the reasons underlying this decision, qualitative
      interviews were carried out with 12 long-term non-attenders. Three distinct
      groups emerged differing in terms of their cognitive and emotional responses to
      diabetes and their coping strategies: (1) the 'High fear' group; (2) the 'Patient
      as expert' group; and (3) the 'Low motivation' group. These differences should be
      recognized and suitable approaches developed to ensure that all people with
      diabetes are able to accept appropriate specialist support.

PMID- 15857872
TI  - The social meanings of prosthesis use.
AB  - The present research explores the social meanings surrounding the use of
      artificial limbs. Semi-structured email and face-to-face interviews were
      conducted with 35 prosthesis users, along with analysis of the posts made on an
      email discussion group for prosthesis users. This data was subject to an
      Interpretative Phenomenological Analysis. It is concluded that prosthesis use
      plays a social role in the lives of persons with limb loss/absence. The ability
      to conceal such use enabled participants to ward off social stigmatisation that
      in turn enabled their social integration and the reduction of emotional problems
      surrounding such disability.

PMID- 15857873
TI  - The fight for 'health-related normality': a qualitative study of the experiences
      of individuals living with established inflammatory bowel disease (ibd).
AB  - This article reports on the experiences of individuals living with IBD and
      identifies a range of coping strategies used by them. Qualitative data from 15
      individual interviews and three focus groups were analysed using a grounded
      theory approach. The main focus is on the emergent core concept of 'health
      related normality'. A theoretical framework is proposed to explain how
      individuals with IBD assess their health-related normality, their fight to
      maintain it and their need to retain the appearance of normality to others. It is
      concluded that individuals maintain their health-related normality along certain
      time and context sensitive continuums rather than fitting into a distinct
      typology.

PMID- 15857874
TI  - Well-being in rheumatoid arthritis: the effects of disease duration and
      psychosocial factors.
AB  - This study examined the multivariate relationships of psychosocial factors with
      well-being in rheumatoid arthritis (RA). Fifty-five patients with early RA (<six
      months), 52 with intermediate RA (one-seven years) and 47 with established RA
      (>seven years) completed questionnaires on psychosocial factors and psychological
      and physical well-being. Illness perceptions related to worse depression and life
      satisfaction (especially in early RA) and to longer morning stiffness (especially
      in intermediate RA). Optimism related to lower pain in early and intermediate RA.
      Social support related to lower fatigue in established RA. Indications for
      interventions targeted by disease duration are discussed.

PMID- 15857875
TI  - Child labour and the International Labour Organization's Convention 182: a
      critical perspective.
AB  - 'Child labour' is a worldwide problem that has caused detrimental effects to
      children's health and well-being. The ILO Convention 182 aims to address this
      issue by immediately eliminating its worst forms. This article provides a
      discourse analysis of this Convention. The analysis suggests that using an
      organizational discourse, the Convention promotes the maintenance of existing
      hierarchies of power, primarily through emphasis on legislative structures and
      consultation with the Organization of Employers and Workers. It has been
      recommended that the Convention be revised in light of the insights generated by
      the analysis and that the children be given a more active role in the process.

PMID- 15857876
TI  - Fetal homologue of infant crying.
AB  - Four behavioural states are recognised in the human fetus and are comparable to
      those of the neonate: 1F (quiet sleep), 2F (active state), 3F (quiet awake), and
      4F (active awake). State 5, or crying, is not considered to have a fetal
      correlate. In a study assessing the effects of exposure to tobacco and cocaine
      during pregnancy on fetal response and habituation to vibroacoustic stimulation,
      what appears to be the fetal homologue of crying was observed. These behaviours
      were seen on ultrasound, and have been captured on video recordings and include:
      an initial exhalation movement associated with mouth opening and tongue
      depression, followed by a series of three augmented breaths, the last breath
      ending in an inspiratory pause followed by an expiration and settling. This is
      the first report/video documenting these behaviours and suggests the possibility
      of a state 5F.

PMID- 15857877
TI  - Sleeping position and electrocortical activity in low birthweight infants.
AB  - OBJECTIVE: To evaluate the effects of prone and supine sleeping positions on
      electrocortical activity during active (AS) and quiet (QS) sleep in low
      birthweight infants. DESIGN: Randomised/crossover study. SETTING: Infant
      Physiology Laboratory at Children's Hospital of New York. PATIENTS: Sixty three
      healthy, growing, low birthweight (birth weight 795-1600 g) infants, 26-37 weeks
      gestational age. INTERVENTIONS: Six hour continuous two channel electrocortical
      recordings, together with minute by minute behavioural state assignment, were
      performed. The infants were randomly assigned to prone or supine position during
      the first three hours, and positions were reversed during the second three hours.
      OUTCOME MEASURES AND RESULTS: Fast Fourier transforms of electroencephalograms
      (EEGs) were performed each minute and the total EEG power (TP), spectral edge
      frequency (SEF), absolute (AP) and relative (RP) powers in five frequency bands
      (0.01-1.0 Hz, 1-4 Hz, 4-8 Hz, 8-12 Hz, 12-24 Hz) were computed. Mean values for
      TP, SEF, AP, and RP in the five frequency bands in the prone and supine positions
      during AS and QS were then compared. In the prone sleeping position, during AS,
      infants showed significantly lower TP, decreased AP in frequency bands 0.01-1.0
      Hz, 4-8 Hz, 8-12 Hz, 12-24 Hz, increased RP in 1-4 Hz, and a decrease in SEF.
      Similar trends were observed during QS, although they did not reach statistical
      significance. CONCLUSIONS: The prone sleeping position promotes a shift in EEG
      activity towards slower frequencies. These changes in electrocortical activity
      may be related to mechanisms associated with decreased arousal in the prone
      position and, in turn, increased risk of sudden infant death syndrome.

PMID- 15857878
TI  - Computed tomography versus bronchography in the diagnosis and management of
      tracheobronchomalacia in ventilator dependent infants.
AB  - AIM: To assess the relative accuracy of dynamic spiral computed tomography (CT)
      compared with tracheobronchography, in a population of ventilator dependent
      infants with suspected tracheobroncho-malacia (TBM). SETTING: Paediatric
      intensive care unit in a tertiary teaching hospital. PATIENTS AND METHODS:
      Infants referred for investigation and management of ventilator dependence and
      suspected of having TBM were recruited into the study. Tracheobronchography and
      CT were performed during the same admission by different investigators who were
      blinded to the results of the other investigation. The study was approved by the
      hospital research ethics committee, and signed parental consent was obtained.
      RESULTS: Sixteen infants were recruited into the study. Fifteen had been born
      prematurely, and five had cardiovascular malformations. In 10 patients there was
      good or partial correlation between the two investigations, but in six patients
      there was poor or no correlation. Bronchography consistently showed more dynamic
      abnormalities, although CT picked up an unsuspected double aortic arch. Radiation
      doses were 0.27-2.47 mSv with bronchography and 0.86-10.67 mSv with CT.
      CONCLUSIONS: Bronchography was a better investigation for diagnosing TBM and in
      determining opening pressures. Spiral CT is unreliable in the assessment of TBM
      in ventilator dependent infants. In addition, radiation doses were considerably
      higher with CT.

PMID- 15857879
TI  - Aminoglycoside extended interval dosing in neonates is safe and effective: a meta
      analysis.
AB  - OBJECTIVES: To review the evidence from controlled clinical trials of neonates
      given equal daily aminoglycoside doses as extended interval dosing (dosage
      interval typically 24 hours in term and 36-48 hours in immature neonates)
      compared with traditional dosing (dosage interval typically 8-12 hours in term
      and 12-24 hours in immature neonates). DESIGN: Systematic review and meta
      analysis of controlled trials found in electronic databases, trial registers, and
      references in reviews and selected trials. SETTINGS: The selected trials were
      blinded and assessed for methodological quality. Each trial's own predefined
      criteria for treatment failure, nephrotoxicity, ototoxicity, and therapeutic
      serum drug concentrations were used. SUBJECTS: Controlled trials of neonatal
      aminoglycoside treatment in which equal aminoglycoside daily doses were given at
      traditional and extended dosage intervals. MAIN OUTCOME MEASURES: Serum drug
      concentrations outside the therapeutic range. Treatment failure and toxicity.
      RESULTS: Sixteen trials involving 823 neonates met the inclusion criteria for the
      systematic review. Twelve trials involving 698 neonates were included in the meta
      analysis of the pharmacokinetics. Compared with traditional dosing, extended
      interval dosing was associated with a significantly lower risk of both peak
      (summary risk ratio 0.50, 95% confidence interval 0.26 to 0.94) and trough (0.36,
      0.25 to 0.56) serum drug concentrations outside the therapeutic range. Accurate
      information on treatment failure was obtained in nine trials involving 555
      neonates. One trial reported treatment failure. In this trial two neonates in the
      traditional dosing group did not respond to treatment within 72 hours.
      Nephrotoxicity was investigated in 589 neonates in 12 trials and ototoxicity in
      210 neonates in four trials, with no significant differences between the two
      dosing regimens. CONCLUSIONS: Extended interval dosing of aminoglycosides in
      neonates is safe and effective, with a reduced risk of serum drug concentrations
      outside the therapeutic range.

PMID- 15857880
TI  - Maspin alters the carcinoma proteome.
AB  - Maspin, a member of the serine protease inhibitor (serpin) family, is a tumor
      suppressor in breast and prostate cancer. To address molecular mechanisms
      underlying maspin's activity, we restored its expression in invasive carcinoma
      cells and analyzed the resulting changes by shotgun proteomics. Using a mass
      spectrometry-based multidimensional proteomic method, we observed changes to the
      expression of approximately 27% of the detectable proteome. In particular, we
      noted changes to the expression of proteins that regulate cytoskeletal
      architecture, cell death, and protein turnover. In each case, changes in protein
      expression were accompanied by measurable changes in tumor cell phenotype. Thus,
      maspin-expressing cells exhibit a more prominent actin cytoskeleton, a reduced
      invasive capacity, an increased rate of spontaneous apoptosis, and an altered
      proteasome function. These observations reveal for the first time the far
      reaching effects of maspin on multiple protein networks and a new hypothesis of
      maspin function based on the regulation of proteasome function.

PMID- 15857881
TI  - Mesenchymal stem cells from the outer ear: a novel adult stem cell model system
      for the study of adipogenesis.
AB  - Adipocytes arise from multipotent stem cells of mesodermal origin, which also
      give rise to the muscle, bone, and cartilage lineages. However, signals and early
      molecular events that commit multipotent stem cells into the adipocyte lineage
      are not well established mainly due to lack of an adequate model system. We have
      identified a novel source of adult stem cells from the external murine ears
      referred to here as an ear mesenchymal stem cells (EMSC). EMSC have been isolated
      from several standard and mutant strains of mice. They are self-renewing,
      clonogenic, and multipotent, since they give rise to osteocytes, chondrocytes,
      and adipocytes. The in vitro characterization of EMSC indicates very facile
      adipogenic differentiation. Morphological, histochemical, and molecular analysis
      after the induction of differentiation showed that EMSC maintain adipogenic
      potentials up to fifth passage. A comparison of EMSC to the stromal-vascular (S
      V) fraction of fat depots, under identical culture conditions (isobutyl
      methylxanthine, dexamethasone, and insulin), revealed much more robust and
      consistent adipogenesis in EMSC than in the S-V fraction. In summary, we show
      that EMSC can provide a novel, easily obtainable, primary culture model for the
      study of adipogenesis.

PMID- 15857882
TI  - From conference abstract to full paper: differences between data presented in
      conferences and journals.
AB  - BACKGROUND: We studied the type and frequency of differences between data
      presented in conference abstracts and subsequent published papers in the fields
      of infectious diseases and microbiology. METHODS: We reviewed all abstracts from
      the first session of 7 of 15 major research categories presented in the 1999 and
      2000 Interscience Conference on Antimicrobial Agents and Chemotherapy. For each
      selected pair of abstract and related published paper, two independent
      investigators performed a detailed data comparison. RESULTS: From 190 abstracts
      reviewed, 68 (36%) were subsequently published as full papers by March 2004.
      Fifty-two pairs referred to the same study population and period. Differences
      were found in 30 of 51 pairs, which were further analyzed (point estimate=59%,
      95% C.I.: 45-73%). The identified differences were related to both the aims and
      conclusions of the study (3/30), the study conclusions only (2/30), numbers
      and/or rates of the studied patients (10/30), numbers or rates of microbiological
      isolates (9/30), MIC values or K(i) values (5/30), other pharmacological
      properties of antibiotics (2/30), odds ratio (1/30), and duration of observation
      (1/30). Some differences were considered major. In bivariable associations, time
      to publication (from presentation in the conference to publication of the full
      paper) was associated with identifiable differences between the conference
      abstract and the full paper (OR=1.76, 95% CI 0.95-3.24/year of delay, P=0.07).
      CONCLUSIONS: It is reassuring that although we identified several reportable
      differences, only a very small proportion of studies exhibited differences in
      their aims and/or conclusions. Researchers may benefit from the above findings in
      improving the accuracy of presented data.

PMID- 15857883
TI  - HLA-G and immune tolerance in pregnancy.
AB  - Multiple mechanisms underlie the surprising willingness of mothers to tolerate
      genetically different fetal tissues during pregnancy. Chief among these is the
      choice of HLA-G, a gene with few alleles, rather than the highly polymorphic HLA
      A and -B genes, for expression by the placental cells that interface directly
      with maternal blood and tissues. Novel aspects of this major histocompatibility
      complex class Ib gene include alternative splicing to permit production of
      membrane and soluble isoforms, deletions that dampen responses to interferons,
      and a shortened cytoplasmic tail that affects expression at the cell surface.
      Placental cells migrating into the maternal uterus synthesize both membrane and
      soluble isoforms, which interact with inhibitory receptors on leukocytes such as
      ILT2 and ILT4. Cytotoxic T lymphocytes either die or reduce production of one of
      their major coreceptor/activator cell surface molecules, CD8; natural killer
      cells are immobilized and mononuclear phagocytes are programmed into suppressive
      modes characterized by high production of anti-inflammatory cytokines. The idea
      that placental HLA-G proteins facilitate semiallogeneic pregnancy by inhibiting
      maternal immune responses to foreign (paternal) antigens via these actions on
      immune cells is now well established, and the postulate that the recombinant
      counterparts of these proteins may be used as powerful tools for preventing
      immune rejection of transplanted organs is gaining in popularity.

PMID- 15857884
TI  - Defining the role of olfactory ensheathing cells in facilitating axon
      remyelination following damage to the spinal cord.
AB  - Olfactory ensheathing cells (OECs) are unique cells that are responsible for the
      successful regeneration of olfactory axons throughout the life of adult mammals.
      More than a decade of research has shown that implantation of OECs may be a
      promising therapy for damage to the nervous system, including spinal cord injury.
      Based on this research, several clinical trials worldwide have been initiated
      that use autologous transplantation of olfactory tissue containing OECs into the
      damaged spinal cord of humans. However, research from several laboratories has
      challenged the widely held belief that OECs are directly responsible for
      myelinating axons and promoting axon regeneration. The purpose of this review is
      to provide a working hypothesis that integrates several current ideas regarding
      the mechanisms of the beneficial effects of OECs. Specifically, OECs promote axon
      regeneration and functional recovery indirectly by augmenting the endogenous
      capacity of host Schwann cells to invade the damaged spinal cord. Together with
      Schwann cells, OECs create a 3-dimensional matrix that provides a permissive
      microenvironment for successful axon regeneration in the adult mammalian central
      nervous system.

PMID- 15857885
TI  - More than just strand breaks: the recognition of structural DNA discontinuities
      by DNA-dependent protein kinase catalytic subunit.
AB  - The DNA-dependent protein kinase (DNA-PK) is a trimeric factor originally
      identified as an enzyme that becomes activated upon incubation with DNA. Genetic
      defects in either the catalytic subunit (DNA-PK(CS)) or the two Ku components of
      DNA-PK result in immunodeficiency, radiosensitivity, and premature aging. This
      combined phenotype is generally attributed to the requirement for DNA-PK in the
      repair of DNA double strand breaks during various biological processes. However,
      recent studies revealed that DNA-PK(CS), a member of the growing family of
      phosphatidylinositol 3-kinases, participates in signal transduction cascades
      related to apoptotic cell death, telomere maintenance and other pathways of
      genome surveillance. These manifold functions of DNA-PK(CS) have been associated
      with an increasing number of protein interaction partners and phosphorylation
      targets. Here we review the DNA binding properties of DNA-PK(CS) and highlight
      its ability to interact with an astounding diversity of nucleic acid substrates.
      This survey indicates that the large catalytic subunit of DNA-PK functions as a
      sensor of not only broken DNA molecules, but of a wider spectrum of aberrant,
      unusual, or specialized structures that interrupt the standard double helical
      conformation of DNA.

PMID- 15857886
TI  - Physiological role of collagen XVIII and endostatin.
AB  - Collagen XVIII is a component of basement membranes (BMs) with the structural
      properties of both a collagen and a proteoglycan. Proteolytic cleavage within its
      C-terminal domain releases a fragment, endostatin, which has been reported to
      have anti-angiogenesis effects. Molecular studies demonstrated binding of the
      endostatin domain to heparan sulfate and to BM components like laminin and
      perlecan, but the functional role of these interactions in vivo remains unknown.
      Insights into the physiological function of collagen XVIII/endostatin have
      recently been obtained through the identification of inactivating mutations in
      the human collagen XVIII/endostatin gene (COL18A1) in patients with Knobloch
      syndrome, characterized by age-dependent vitreoretinal degeneration and occipital
      encephalocele. That collagen XVIII/endostatin has an essential role in ocular
      development and the maintenance of visual function is further demonstrated by the
      ocular abnormalities seen in mice lacking collagen XVIII/endostatin. Age
      dependent loss of vision in these mutant mice is associated with pathological
      accumulation of deposits under the retinal pigment epithelium, as seen in early
      stages of age-related macular degeneration in humans. In addition, recent
      evidence suggests that lack of collagen XVIII/endostatin predisposes to
      hydrocephalus formation. These recent findings demonstrate an important role for
      collagen XVIII/endostatin in cell-matrix interactions in certain tissues that may
      be compensated for in other tissues expressing this collagen.

PMID- 15857887
TI  - Individual domains of connective tissue growth factor regulate fibroblast
      proliferation and myofibroblast differentiation.
AB  - All members of the Ctgf, Cyr61, and Nov (CCN) family share a high degree of
      sequence homology and conservation of structural motifs and domains. Here, we
      present data about a structure function analysis of connective tissue growth
      factor (CTGF), a prototypic member of the CCN family, which has been shown to be
      a downstream mediator of transforming growth factor-beta activities on
      fibroblasts. Our findings demonstrate the two domains of CTGF function to mediate
      two distinct biological effects. The N-terminal domain of CTGF mediates
      myofibroblast differentiation and collagen synthesis. The C-terminal domain of
      CTGF mediates fibroblast proliferation. These data provide a molecular basis for
      the divergence of CTGF actions on connective tissue cell types and suggest a
      model for functional analysis of all of the CCN family gene products.

PMID- 15857888
TI  - Distinct transcriptional regulation and function of the human BACE2 and BACE1
      genes.
AB  - Amyloid beta protein (Abeta) is the principal component of neuritic plaques in
      Alzheimer's disease (AD). Abeta is derived from beta amyloid precursor protein
      (APP) by beta- and gamma-secretases. Beta-site APP cleaving enzyme 1 (BACE1) has
      been identified as the major beta-secretase. BACE2 is the homolog of BACE1. The
      BACE2 gene is on chromosome 21 and has been implicated in the pathogenesis of AD.
      However, the function of BACE2 in Abeta generation is controversial. Some studies
      have shown that BACE2 cleaved APP at the beta-site whereas other studies showed
      it cleaved around the alpha-secretase site. To elucidate the involvement of BACE2
      in AD pathogenesis, we compared BACE2 and BACE1 gene regulation and their
      functions in Abeta generation. We cloned and functionally characterized the human
      BACE2 promoter. The BACE2 gene is controlled by a TATA-less promoter. Though Sp1
      can regulate both BACE1 and BACE2 genes, comparative sequence analysis and
      transcription factor prediction showed little similarity between the two
      promoters. BACE1 increased APP cleavage at the beta-site and Abeta production
      whereas BACE2 did not. Overexpression of BACE2 significantly increased sAPP
      levels in conditioned media but markedly reduced Abeta production. Knockdown of
      BACE2 resulted in increased APP C83. Our data indicate that despite being
      homologous in amino acid sequence, BACE2 and BACE1 have distinct functions and
      transcriptional regulation. BACE2 is not a beta-secretase, but processes APP
      within the Abeta domain at a site downstream of the alpha-secretase cleavage
      site. Our data argue against BACE2 being involved in the formation of neuritic
      plaques in AD.

PMID- 15857889
TI  - Human muscle gene expression responses to endurance training provide a novel
      perspective on Duchenne muscular dystrophy.
AB  - Global gene expression profiling is used to generate novel insight into a variety
      of disease states. Such studies yield a bewildering number of data points, making
      it a challenge to validate which genes specifically contribute to a disease
      phenotype. Aerobic exercise training represents a plausible model for
      identification of molecular mechanisms that cause metabolic-related changes in
      human skeletal muscle. We carried out the first transcriptome-wide
      characterization of human skeletal muscle responses to 6 wk of supervised aerobic
      exercise training in 8 sedentary volunteers. Biopsy samples before and after
      training allowed us to identify approximately 470 differentially regulated genes
      using the Affymetrix U95 platform (80 individual hybridization steps). Gene
      ontology analysis indicated that extracellular matrix and calcium binding gene
      families were most up-regulated after training. An electronic reanalysis of a
      Duchenne muscular dystrophy (DMD) transcript expression dataset allowed us to
      identify approximately 90 genes modulated in a nearly identical fashion to that
      observed in the endurance exercise dataset. Trophoblast noncoding RNA, an
      interfering RNA species, was the singular exception-being up-regulated by
      exercise and down-regulated in DMD. The common overlap between gene expression
      datasets may be explained by enhanced alpha7beta1 integrin signaling, and
      specific genes in this signaling pathway were up-regulated in both datasets. In
      contrast to these common features, OXPHOS gene expression is subdued in DMD yet
      elevated by exercise, indicating that more than one major mechanism must exist in
      human skeletal muscle to sense activity and therefore regulate gene expression.
      Exercise training modulated diabetes-related genes, suggesting our dataset may
      contain additional and novel gene expression changes relevant for the anti
      diabetic properties of exercise. In conclusion, gene expression profiling after
      endurance exercise training identified a range of processes responsible for the
      physiological remodeling of human skeletal muscle tissue, many of which were
      similarly regulated in DMD. Furthermore, our analysis demonstrates that numerous
      genes previously suggested as being important for the DMD disease phenotype may
      principally reflect compensatory integrin signaling.

PMID- 15857890
TI  - Chronic expression of monocyte chemoattractant protein-1 in the central nervous
      system causes delayed encephalopathy and impaired microglial function in mice.
AB  - Increased central nervous system (CNS) levels of monocyte chemoattractant protein
      1 [CC chemokine ligand 2 (CCL2) in the systematic nomenclature] have been
      reported in chronic neurological diseases such as human immunodeficiency virus
      type 1-associated dementia, amyotrophic lateral sclerosis, and multiple
      sclerosis. However, a pathogenic role for CCL2 has not been confirmed, and there
      is no established model for the effects of chronic CCL2 expression on resident
      and recruited CNS cells. We report that aged (>6 months) transgenic (tg) mice
      expressing CCL2 under the control of the human glial fibrillary acidic protein
      promoter (huGFAP-CCL2hi tg+ mice) manifested encephalopathy with mild
      perivascular leukocyte infiltration, impaired blood brain barrier function, and
      increased CD45-immunoreactive microglia, which had morphologic features of
      activation. huGFAP-CCL2hi tg+ mice lacking CC chemokine receptor 2 (CCR2) were
      normal, showing that chemokine action via CCR2 was required. Studies of cortical
      slice preparations using video confocal microscopy showed that microglia in the
      CNS of huGFAP-CCL2hi tg+ mice were defective in expressing amoeboid morphology.
      Treatment with mutant CCL2 peptides, a receptor antagonist and an obligate
      monomer, also suppressed morphological transformation in this assay, indicating a
      critical role for CCL2 in microglial activation and suggesting that chronic CCL2
      exposure desensitized CCR2 on microglia, which in the CNS of huGFAP-CCL2hi tg+
      mice, did not up-regulate cell-surface expression of major histocompatibility
      complex class II, CD11b, CD11c, or CD40, in contrast to recruited perivascular
      macrophages that expressed enhanced levels of these markers. These results
      indicate that huGFAP-CCL2hi tg+ mice provide a useful model to study how chronic
      CNS expression of CCL2 alters microglial function and CNS physiology.

PMID- 15857891
TI  - 5'-AMP-activated protein kinase regulates skeletal muscle glycogen content and
      ergogenics.
AB  - 5'-AMP-activated protein kinase (AMPK) activity is increased during exercise in
      an intensity- and glycogen-dependent manner. We previously reported that a
      mutation in the AMPK3 subunit (Prkag3225Q) increases AMPK activity and skeletal
      muscle glycogen content. Transfection experiments revealed the R225Q mutation is
      associated with high basal AMPK activity and diminished AMP dependence. Thus, the
      R225Q mutation can be considered a loss-of-function mutation that abolished
      allosteric regulation by AMP/ATP, causing increased basal AMPK activity. We used
      AMPK3 transgenic (Tg-Prkag3225Q) and knockout (Prkag3-/-) mice to determine the
      relationship between AMPK activity, glycogen content, and ergogenics (ability to
      perform work) in isolated extensor digitorum longus skeletal muscle after
      contractions induced by electrical stimulation. Contraction-induced AMPK activity
      was inversely coupled to glycogen content in wild-type and Tg-Prkag3225Q mice,
      but not in Prkag3-/- mice, highlighting a partial feedback control of glycogen on
      contraction-induced AMPK activity in the presence of a functional AMPK3 isoform.
      Skeletal muscle glycogen content was positively correlated to work performance,
      regardless of genotype. Thus, chronic activation of AMPK by the Prkag3225Q
      mutation directly influences skeletal muscle ergogenics by enhancing glycogen
      content. In conclusion, functional studies of the AMPK3 isoform further support
      the close connection between glycogen content and exercise performance in
      skeletal muscle.

PMID- 15857892
TI  - GPR4 plays a critical role in endothelial cell function and mediates the effects
      of sphingosylphosphorylcholine.
AB  - Angiogenesis is critical for many physiological and pathological processes. We
      show here that the lipid sphingosylphosphorylcholine (SPC) induces angiogenesis
      in vivo and GPR4 is required for the biological effects of SPC on endothelial
      cells (EC). In human umbilical vein EC, down-regulation of GPR4 specifically
      inhibits SPC-, but not sphingosine-1-phosphate-, or vascular endothelial growth
      factor (VEGF)-induced tube formation. Re-introduction of GPR4 fully restores the
      activity of SPC. In microvascular EC, GPR4 plays a pivotal role in cell survival,
      growth, migration, and tube formation through both SPC-dependent and -independent
      pathways. The biological effects resulting from SPC/GPR4 interactions involve the
      activation of both phosphatidylinositol-3 kinase and Akt. Moreover, the effects
      of SPC on EC require SPC induced trans-phosphorylation and activation of the VEGF
      receptor 2. These results identify SPC and its receptor, GPR4, as critical
      regulators of the angiogenic potential of EC.

PMID- 15857893
TI  - Hydrogen peroxide is a diffusible paracrine signal for the induction of
      epithelial cell death by activated myofibroblasts.
AB  - Cell-cell signaling roles for reactive oxygen species (ROS) generated in response
      to growth factors/cytokines in nonphagocytic cells are not well defined. In this
      study, we show that fibroblasts isolated from lungs of patients with idiopathic
      pulmonary fibrosis (IPF) generate extracellular hydrogen peroxide (H2O2) in
      response to the multifunctional cytokine, transforming growth factor-beta1 (TGF
      beta1). In contrast, TGF-beta1 stimulation of small airway epithelial cells
      (SAECs) does not result in detectable levels of extracellular H2O2. IPF
      fibroblasts independently stimulated with TGF-beta1 induce loss of viability and
      death of overlying SAECs when cocultured in a compartmentalized Transwell system.
      These effects on SAECs are inhibited by the addition of catalase to the coculture
      system or by the selective enzymatic blockade of H2O2 production by IPF
      fibroblasts. IPF fibroblasts heterogeneously express alpha-smooth muscle actin
      stress fibers, a marker of myofibroblast differentiation. Cellular localization
      of H2O2 by a fluorescent-labeling strategy demonstrated that extracellular
      secretion of H2O2 is specific to the myofibroblast phenotype. Thus, myofibroblast
      secretion of H2O2 functions as a diffusible death signal for lung epithelial
      cells. This novel mechanism for intercellular ROS signaling may be important in
      physiological/pathophysiological processes characterized by regenerating
      epithelial cells and activated myofibroblasts.

PMID- 15857894
TI  - The Esso prize.

PMID- 15857895
TI  - Ergonomics and musculoskeletal disorders: overview.
AB  - Musculoskeletal disorders continue to be a major source of disability and lost
      work time. Understanding their causes, and especially those that are work
      related, remains the key to primary prevention. This set of in-depth reviews
      considers the problem from a number of systems needs and viewpoints. Assessing
      the exposure of workers to known risk factors is essential and appropriate
      methods are reviewed. Similarly, a consideration of psychosocial factors thought
      to contribute indirectly to the problem has also been explored. Contemporary
      ergonomics stresses the importance of a participatory approach to prevention and
      solution finding, and evidence in support of this is presented. The final review
      considers the application of ergonomics knowledge to understanding
      musculoskeletal disorders amongst those using computer technology.

PMID- 15857896
TI  - Ergonomics, musculoskeletal disorders and computer work.
AB  - This review summarizes the knowledge regarding ergonomics and musculoskeletal
      disorders and the association with computer work. A model of musculoskeletal
      disorders and computer work is proposed and the evidence and implications of the
      model together with issues for future research is discussed. The model emphasizes
      the associations between work organization, psychosocial factors and mental
      stress on the one hand and physical demands and physical load on the other. It is
      hypothesized that perceived muscular tension is an early sign of musculoskeletal
      disorder, which arises as a result of work organizational and psychosocial
      factors as well as from physical load and individual factors. It is further
      hypothesized that perceptions of exertion and comfort are other possible early
      signs of musculoskeletal disorders in computer work. Interventions aimed at
      reducing musculoskeletal disorders due to computer work should be directed at
      both physical/ergonomic factors and work organizational and psychosocial factors.
      Interventions should be carried out with management support and active
      involvement of the individual workers.

PMID- 15857897
TI  - Work-related musculoskeletal health and social support.
AB  - BACKGROUND: This review concerns the relationship between inequalities
      experienced at work with respect to social support (e.g. poor communication
      channels, unsatisfactory work relationships, unsupportive organizational culture)
      and work-related musculoskeletal ill-health. METHODS: Cross-sectional, case
      control and prospective studies, published between 1985 and 2003, that
      investigated this association were selected and reviewed. RESULTS: Studies varied
      greatly in the breadth of definitions of social support used and many measures
      were employed for the collection of data. There is good evidence for an
      association between poor social support and an increased risk in musculoskeletal
      morbidity. There is also limited evidence that poor social support is associated
      with musculoskeletal sickness absence, restricted activity and not returning to
      work after a musculoskeletal problem. A small number of studies have shown the
      effects of good social support and its importance in protecting against
      musculoskeletal ill-health and helping workers cope with problems. CONCLUSIONS:
      The overall findings of this review have implications for the design of proactive
      broad-based prevention programmes and organizational policies for the management
      of musculoskeletal ill-health and its potential outcomes, i.e. sickness absence
      and early retirement. Further research, using stronger study designs and more
      concise definitions of social support, to investigate the importance of social
      support in the amelioration of musculoskeletal ill-health is identified, e.g. the
      contribution of social support received away from the workplace.

PMID- 15857898
TI  - Ergonomic methods for assessing exposure to risk factors for work-related
      musculoskeletal disorders.
AB  - BACKGROUND: This review provides an overview of the range of methods that have
      been developed for the assessment of exposure to risk factors for work-related
      musculoskeletal disorders. METHODS: Relevant publications and material on
      exposure assessment techniques have been gathered for inclusion in this review.
      RESULTS: The methods have been categorized under three main headings: (1) self
      reports from workers can be used to collect data on workplace exposure to both
      physical and psychosocial factors by using methods that include worker diaries,
      interviews and questionnaires; (2) observational methods that may be further
      subdivided between (a) simpler techniques developed for systematically recording
      workplace exposure that enable an observer to assess and record data on a number
      of factors using specifically designed pro-forma sheets for establishing
      priorities for workplace intervention; and (b) advanced techniques developed for
      the assessment of postural variation for highly dynamic activities that record
      data either on videotape or are computer analysed using dedicated software; (3)
      direct measurements using monitoring instruments that rely on sensors attached
      directly to the subject for the measurement of exposure variables at work.
      CONCLUSIONS: The choice between the methods available will depend upon the
      application concerned and the objectives of the study. General, observation-based
      assessments appear to provide the levels of costs, capacity, versatility,
      generality and exactness best matched to the needs of occupational safety and
      health practitioners (or those from related professions) who have limited time
      and resources at their disposal and need a basis for establishing priorities for
      intervention.

PMID- 15857899
TI  - Finding ergonomic solutions--participatory approaches.
AB  - This paper gives an overview of the theory of participatory ergonomics
      interventions and summary examples from a range of industries, including health
      care, military, manufacturing, production and processing, services, construction
      and transport. The definition of participatory approaches includes interventions
      at macro (organizational, systems) levels as well as micro (individual), where
      workers are given the opportunity and power to use their knowledge to address
      ergonomic problems relating to their own working activities. Examples are given
      where a cost-effective benefit has been measured using musculoskeletal sickness
      absence and compensation costs. Other examples, using different outcome measures,
      also showed improvements, for example, an increase in productivity, improved
      communication between staff and management, reduction in risk factors, the
      development of new processes and new designs for work environments and
      activities. Three cases are described from Canada and Japan where the
      participatory project was led by occupational health teams, suggesting that
      occupational health practitioners can have an important role to play in
      participatory ergonomics projects.

PMID- 15857900
TI  - Respiratory symptoms, immunology and organism identification in contaminated
      metalworking fluid workers. What you see is not what you get.
AB  - BACKGROUND: Metal working fluids (MWF) constitute a significant respiratory
      hazard, although symptoms experienced by workers are often poorly investigated
      and attributed. AIMS: A single possible case of extrinsic allergic alveolitis
      (EAA) led to a formal workplace investigation. It was clear that other exposed
      workers were affected. The aim of this study was to accurately quantify the
      clinical, immunological and microbiological findings in MWF workers following
      presentation of a sentinel case. METHODS: Eleven of 21 individuals participated;
      eight were assessed by symptom questionnaire, spirometry and serology and three
      workers provided blood samples only. The microbes cultured from MWF and air
      samples were used to determine the presence of precipitating antibodies. RESULTS:
      Work-related respiratory symptoms were reported in six of eight individuals
      questioned, two of these complaining of 'flu-like' symptoms. Personal breathing
      zone measures identified 2.1 x 10(3) to 1.1 x 10(5) colony-forming units/m3 air
      (CFU/m3). Pseudomonas fluorescens was isolated from air samples. Despite visible
      'fungal' contamination of MWF, airborne fungi were detectable in only one sample,
      at 486 CFU/m3 air. MWF cultured Eurotium sp., Fusarium sp. and Pseudomonas sp.
      Precipitating IgG antibodies to Pseudomonas sp. were identified in 4/11 and to an
      extract of the MWF in 3/11. IgG to Pseudomonas was elevated in the two
      individuals who had the strongest precipitating bands to Pseudomonas sp.
      CONCLUSIONS: Workplaces with possible EAA must be investigated promptly, thus
      allowing clinical assessment to be contemporary to exposures and accurate
      microbiological profiling included to identify the likely cause.

PMID- 15857902
TI  - Inositol polyphosphate derivative inhibits Na+ transport and improves fluid
      dynamics in cystic fibrosis airway epithelia.
AB  - Amiloride-sensitive, epithelial Na(+) channel (ENaC)-mediated, active absorption
      of Na(+) is elevated in the airway epithelium of cystic fibrosis (CF) patients,
      resulting in excess fluid removal from the airway lumen. This excess fluid/volume
      absorption corresponds to CF transmembrane regulator-linked defects in ENaC
      regulation, resulting in the reduced mucociliary clearance found in CF airways.
      Herein we show that INO-4995, a synthetic analog of the intracellular signaling
      molecule, D-myo-inositol 3,4,5,6-tetrakisphosphate, inhibits Na(+) and fluid
      absorption across CF airway epithelia, thus alleviating this critical pathology.
      This conclusion was based on electrophysiological studies, fluid absorption, and
      (22)Na(+) flux measurements in CF airway epithelia, contrasted with normal
      epithelia, and on electrophysiological studies in Madin-Darby canine kidney cells
      and 3T3 cells overexpressing ENaC. The effects of INO-4995 were long-lasting,
      dose-dependent, and more pronounced in epithelia from CF patients vs. controls.
      These findings support preclinical development of INO-4995 for CF treatment and
      demonstrate for the first time the therapeutic potential of inositol
      polyphosphate derivatives.

PMID- 15857903
TI  - Flow cytometric method for enumeration and characterization of newly released
      polymorphonuclear leukocytes from the bone marrow using 5'-bromo-2'-deoxyuridine.
AB  - Inflammation accelerates polymorphonuclear leukocyte (PMN) release from the bone
      marrow, and these PMNs are implicated in inappropriate tissue injury. We have
      previously developed a method using 5'-bromo-2'-deoxyuridine (BrdU) to study PMN
      kinetics using an immunocytochemical grading system of PMN on cytospin slides.
      The aim of this study was to develop a flow cytometric method to quantify the
      number of positively stained PMN and grade the intensity of staining for the
      transit time calculation of PMN through the marrow. Dividing myeloid progenitors
      in the marrow of rabbits were labeled with a pulse dosage of intravenous BrdU.
      BrdU-labeled PMN (PMN(BrdU)) were detected in the circulation using a FITC
      conjugated anti-BrdU monoclonal antibody. The PMN(BrdU) were assigned to five
      groups according to their FITC intensity, and the transit times of PMN at
      different stages of development in the marrow were calculated. Results were
      compared using parallel immunocytochemical analysis of the same samples. In
      control animals, PMN(BrdU) in the circulation peaked at 72 h after BrdU labeling
      with 36.0% of PMN labeled. In normal rabbits, the transit times of PMN through
      the mitotic pool (49.5 +/- 4.2 h) and maturation pool (65.5 +/- 3.1 h) correlated
      well with immunocytochemical analysis and previously published values. Using this
      method, we demonstrated that exposure to air pollution particles accelerates the
      release of PMN(BrdU) from the marrow. We conclude that a flow cytometric approach
      for identifying BrdU-labeled leukocytes provides an objective and accurate method
      for studying leukocyte kinetics and behavior.

PMID- 15857904
TI  - Degradation of extracellular ATP by the retinal pigment epithelium.
AB  - Stimulation of ATP or adenosine receptors causes important physiological changes
      in retinal pigment epithelial (RPE) cells that may influence their relationship
      to the adjacent photoreceptors. While RPE cells have been shown to release ATP,
      the regulation of extracellular ATP levels and the production of dephosphorylated
      purines is not clear. This study examined the degradation of ATP by RPE cells and
      the physiological effects of the adenosine diphosphate (ADP) that result. ATP was
      readily broken down by both cultured human ARPE-19 cells and the apical membrane
      of fresh bovine RPE cells. The compounds ARL67156 and betagamma-mATP inhibited
      this degradation in both cell types. RT-PCR analysis of ARPE-19 cells found mRNA
      message for multiple extracellular degradative enzymes; ectonucleotide
      pyrophosphatase/phosphodiesterase eNPP1, eNPP2, and eNPP3; the ectoATPase
      ectonucleoside triphosphate diphosphohydrolase NTPDase2, NTPDase3, and some
      message for NTPDase1. Considerable levels of ADP bathed RPE cells, consistent
      with a role for NTPDase2. ADP and ATP increased levels of intracellular Ca(2+).
      Both responses were inhibited by thapsigargin and P2Y(1) receptor inhibitor MRS
      2179. Message for both P2Y(1) and P2Y(12) receptors was detected in ARPE-19
      cells. These results suggest that extracellular degradation of ATP in subretinal
      space can result in the production of ADP. This ADP can stimulate P2Y receptors
      and augment Ca(2+) signaling in the RPE.

PMID- 15857905
TI  - Depolarization induces Rho-Rho kinase-mediated myosin light chain phosphorylation
      in kidney tubular cells.
AB  - Myosin-based contractility plays important roles in the regulation of epithelial
      functions, particularly paracellular permeability. However, the triggering
      factors and the signaling pathways that control epithelial myosin light chain
      (MLC) phosphorylation have not been elucidated. Herein we show that plasma
      membrane depolarization provoked by distinct means, including high extracellular
      K(+), the lipophilic cation tetraphenylphosphonium, or the ionophore nystatin,
      induced strong diphosphorylation of MLC in kidney epithelial cells. In sharp
      contrast to smooth muscle, depolarization of epithelial cells did not provoke a
      Ca(2+) signal, and removal of external Ca(2+) promoted rather than inhibited MLC
      phosphorylation. Moreover, elevation of intracellular Ca(2+) did not induce
      significant MLC phosphorylation, and the myosin light chain kinase (MLCK)
      inhibitor ML-7 did not prevent the depolarization-induced MLC response,
      suggesting that MLCK is not a regulated element in this process. Instead, the Rho
      Rho kinase (ROK) pathway is the key mediator because 1) depolarization stimulated
      Rho and induced its peripheral translocation, 2) inhibition of Rho by Clostridium
      difficile toxin B or C3 transferase abolished MLC phosphorylation, and 3) the ROK
      inhibitor Y-27632 suppressed the effect. Importantly, physiological depolarizing
      stimuli were able to activate the same pathway: L-alanine, the substrate of the
      electrogenic Na(+)-alanine cotransporter, stimulated Rho and induced Y-27632
      sensitive MLC phosphorylation in a Na(+)-dependent manner. Together, our results
      define a novel mode of the regulation of MLC phosphorylation in epithelial cells,
      which is depolarization triggered and Rho-ROK-mediated but Ca(2+) signal
      independent. This pathway may be a central mechanism whereby electrogenic
      transmembrane transport processes control myosin phosphorylation and thereby
      regulate paracellular transport.

PMID- 15857906
TI  - Hypoxia alters biophysical properties of endothelial cells via p38 MAPK- and Rho
      kinase-dependent pathways.
AB  - Hypoxia alters the barrier function of the endothelial cells that line the
      pulmonary vasculature, but underlying biophysical mechanisms remain unclear.
      Using rat pulmonary microvascular endothelial cells (RPMEC) in culture, we report
      herein changes in biophysical properties, both in space and in time, that occur
      in response to hypoxia. We address also the molecular basis of these changes. At
      the level of the single cell, we measured cell stiffness, the distribution of
      traction forces exerted by the cell on its substrate, and spontaneous nanoscale
      motions of microbeads tightly bound to the cytoskeleton (CSK). Hypoxia increased
      cell stiffness and traction forces by a mechanism that was dependent on the
      activation of Rho kinase. These changes were followed by p38-mediated decreases
      in spontaneous bead motions, indicating stabilization of local cellular
      extracellular matrix (ECM) tethering interactions. Cells overexpressing phospho
      mimicking small heat shock protein (HSP27-PM), a downstream effector of p38,
      exhibited decreases in spontaneous bead motions that correlated with increases in
      actin polymerization in these cells. Together, these findings suggest that
      hypoxia differentially regulates endothelial cell contraction and cellular-ECM
      adhesion.

PMID- 15857907
TI  - PKC-delta sensitizes Kir3.1/3.2 channels to changes in membrane phospholipid
      levels after M3 receptor activation in HEK-293 cells.
AB  - G protein-gated inward rectifier (Kir3) channels are inhibited by activation of
      G(q/11)-coupled receptors and this has been postulated to involve the signaling
      molecules protein kinase C (PKC) and/or phosphatidylinositol 4,5-bisphosphate
      (PIP(2)). Their precise roles in mediating the inhibition of this family of
      channels remain controversial. We examine here their relative roles in causing
      inhibition of Kir3.1/3.2 channels stably expressed in human embryonic kidney
      (HEK)-293 cells after muscarinic M(3) receptor activation. In perforated patch
      mode, staurosporine prevented the G(q/11)-mediated, M(3) receptor, inhibition of
      channel activity. Recovery from M(3)-mediated inhibition was wortmannin
      sensitive. Whole cell currents, where the patch pipette was supplemented with
      PIP(2), were still irreversibly inhibited by M(3) receptor stimulation. When
      adenosine A(1) receptors were co-expressed, inclusion of PIP(2) rescued the A(1)
      mediated response. Recordings from inside-out patches showed that catalytically
      active PKC applied directly to the intracellular membrane face inhibited the
      channels: a reversible effect modulated by okadaic acid. Generation of mutant
      heteromeric channel Kir3.1S185A/Kir3.2C-S178A, still left the channel susceptible
      to receptor, pharmacological, and direct kinase-mediated inhibition.
      Biochemically, labeled phosphate is incorporated into the channel. We suggest
      that PKC-delta mediates channel inhibition because recombinant PKC-delta
      inhibited channel activity, M(3)-mediated inhibition of the channel, was
      counteracted by overexpression of two types of dominant negative PKC-delta
      constructs, and, by using confocal microscopy, we have demonstrated translocation
      of green fluorescent protein-tagged PKC-delta to the plasma membrane on M(3)
      receptor stimulation. Thus Kir3.1/3.2 channels are sensitive to changes in
      membrane phospholipid levels but this is contingent on the activity of PKC-delta
      after M(3) receptor activation in HEK-293 cells.

PMID- 15857908
TI  - An example of health education in the early 17th century: Naturall and artificial
      Directions for Health by William Vaughan.
AB  - In 1600, William Vaughan, a Doctor of Civil Laws, published the first edition of
      his health education manual entitled Naturall and artificial Directions for
      Health. In all, seven editions appeared over the next 33 years. Changes were made
      to the title and contents, but the same six general areas were covered in each,
      i.e. (1) Air, fire and water, (2) Food and drink, (3) Sleep and early rising, (4)
      Evacuations, (5) Infirmities and death, and (6) Restoration of health. Although
      Vaughan was writing before the scientific revolution, and had to base his advice
      on the current theories of the four humours, miasma, stars and the supernatural,
      research over the intervening four centuries has proven many of his messages to
      be correct, e.g. clean air and water, a balanced diet, olive oil, low animal fat,
      red wine, fibre, exercise, and avoiding tobacco use, to mention but a few. In
      Vaughan's day, these messages were new to many readers and the method of health
      education used was simply to present the information for people to act on.
      Behavioural research carried out in the last century has changed the approach to
      health education by involving decision-making processes, self-efficacy building
      and social support.

PMID- 15857909
TI  - Essential role of non-canonical Wnt signalling in neural crest migration.
AB  - Migration of neural crest cells is an elaborate process that requires the
      delamination of cells from an epithelium and cell movement into an extracellular
      matrix. In this work, it is shown for the first time that the non-canonical Wnt
      signalling [planar cell polarity (PCP) or Wnt-Ca2+] pathway controls migration of
      neural crest cells. By using specific Dsh mutants, we show that the canonical Wnt
      signalling pathway is needed for neural crest induction, while the non-canonical
      Wnt pathway is required for neural crest migration. Grafts of neural crest tissue
      expressing non-canonical Dsh mutants, as well as neural crest cultured in vitro,
      indicate that the PCP pathway works in a cell-autonomous manner to control neural
      crest migration. Expression analysis of non-canonical Wnt ligands and their
      putative receptors show that Wnt11 is expressed in tissue adjacent to neural
      crest cells expressing the Wnt receptor Frizzled7 (Fz7). Furthermore, loss- and
      gain-of-function experiments reveal that Wnt11 plays an essential role in neural
      crest migration. Inhibition of neural crest migration by blocking Wnt11 activity
      can be rescued by intracellular activation of the non-canonical Wnt pathway. When
      Wnt11 is expressed opposite its normal site of expression, neural crest migration
      is blocked. Finally, time-lapse analysis of cell movement and cell protrusion in
      neural crest cultured in vitro shows that the PCP or Wnt-Ca2+ pathway directs the
      formation of lamellipodia and filopodia in the neural crest cells that are
      required for their delamination and/or migration.

PMID- 15857910
TI  - Requirements of genetic interactions between Src42A, armadillo and shotgun, a
      gene encoding E-cadherin, for normal development in Drosophila.
AB  - Src42A is one of the two Src homologs in Drosophila. Src42A protein accumulates
      at sites of cell-cell or cell-matrix adhesion. Anti-Engrailed antibody staining
      of Src42A protein-null mutant embryos indicated that Src42A is essential for
      proper cell-cell matching during dorsal closure. Src42A, which is functionally
      redundant to Src64, was found to interact genetically with shotgun, a gene
      encoding E-cadherin, and armadillo, a Drosophila beta-catenin.
      Immunoprecipitation and a pull-down assay indicated that Src42A forms a ternary
      complex with E-cadherin and Armadillo, and that Src42A binds to Armadillo repeats
      via a 14 amino acid region, which contains the major autophosphorylation site.
      The leading edge of Src mutant embryos exhibiting the dorsal open phenotype was
      frequently kinked and associated with significant reduction in E-cadherin,
      Armadillo and F-actin accumulation, suggesting that not only Src signaling but
      also Src-dependent adherens-junction stabilization would appear likely to be
      essential for normal dorsal closure. Src42A and Src64 were required for Armadillo
      tyrosine residue phosphorylation but Src activity may not be directly involved in
      Armadillo tyrosine residue phosphorylation at the adherens junction.

PMID- 15857911
TI  - Induction and migration of the anterior visceral endoderm is regulated by the
      extra-embryonic ectoderm.
AB  - The anterior visceral endoderm (AVE) is an extra-embryonic tissue required for
      specifying anterior pattern in the mouse embryo. The AVE is induced at the distal
      tip of the 5.5 dpc embryo and then migrates to the prospective anterior, where it
      imparts anterior identity upon the underlying epiblast (the tissue that gives
      rise to the embryo proper). Little is known about how the AVE is induced and what
      directs its migration. In this paper, we describe an essential role for another
      extra-embryonic tissue, the extra-embryonic ectoderm (ExE), in patterning the AVE
      and epiblast. Removal of the ExE in pre-gastrulation embryos leads to ectopic AVE
      formation, to a failure of AVE cell migration and to the assumption by the entire
      epiblast of an anterior identity. Ectopic transplantation of ExE cells inhibits
      AVE formation and leads to an expansion of the posterior epiblast marker T. These
      results demonstrate that the ExE restricts the induction of the AVE to the distal
      tip of the mouse embryo and is required to initiate the migration of these cells
      to the prospective anterior. Together, these data reveal a novel role for the ExE
      in the specification of the anteroposterior axis of the mouse embryo.

PMID- 15857912
TI  - Perivascular cells expressing annexin A5 define a novel mesenchymal stem cell
      like population with the capacity to differentiate into multiple mesenchymal
      lineages.
AB  - The annexin A5 gene (Anxa5) was recently found to be expressed in the developing
      and adult vascular system as well as the skeletal system. In this paper, the
      expression of an Anxa5-lacZ fusion gene was used to define the onset of
      expression in the vasculature and to characterize these Anxa5-lacZ-expressing
      vasculature-associated cells. After blastocyst implantation, Anxa5-lacZ-positive
      cells were first detected in extra-embryonic tissues and in angioblast
      progenitors forming the primary vascular plexus. Later, expression is highly
      restricted to perivascular cells in most blood vessels resembling pericytes or
      vascular smooth muscle cells. Viable Anxa5-lacZ+ perivascular cells were isolated
      from embryos as well as adult brain meninges by specific staining with
      fluorescent X-gal substrates and cell-sorting. These purified lacZ+ cells
      specifically express known markers of pericytes, but also markers characteristic
      for stem cell populations. In vitro and in vivo differentiation experiments show
      that this cell pool expresses early markers of chondrogenesis, is capable of
      forming a calcified matrix and differentiates into adipocytes. Hence, Anxa5
      expression in perivascular cells from mouse defines a novel population of cells
      with a distinct developmental potential.

PMID- 15857913
TI  - Ssdp1 regulates head morphogenesis of mouse embryos by activating the Lim1-Ldb1
      complex.
AB  - The transcriptional activity of LIM-homeodomain (LIM-HD) proteins is regulated by
      their interactions with various factors that bind to the LIM domain. We show that
      reduced expression of single-stranded DNA-binding protein 1 (Ssdp1), which
      encodes a co-factor of LIM domain interacting protein 1 (Ldb1), in the mouse
      mutant headshrinker (hsk) disrupts anterior head development by partially
      mimicking Lim1 mutants. Although the anterior visceral endoderm and the anterior
      definitive endoderm, which together comprise the head organizer, were able to
      form normally in Ssdp1(hsk/hsk) mutants, development of the prechordal plate was
      compromised. Head development is partially initiated in Ssdp1(hsk/hsk) mutants,
      but neuroectoderm tissue anterior to the midbrain-hindbrain boundary is lost,
      without a concomitant increase in apoptosis. Cell proliferation is globally
      reduced in Ssdp1(hsk/hsk) mutants, and approximately half also exhibit smaller
      body size, similar to the phenotype observed in Lim1 and Ldb1 mutants. We also
      show that Ssdp1 contains an activation domain and is able to enhance
      transcriptional activation through a Lim1-Ldb1 complex in transfected cells, and
      that Ssdp1 interacts genetically with Lim1 and Ldb1 in both head development and
      body growth. These results suggest that Ssdp1 regulates the development of late
      head organizer tissues and body growth by functioning as an essential activator
      component of a Lim1 complex through interaction with Ldb1.

PMID- 15857914
TI  - Dissecting Wnt/beta-catenin signaling during gastrulation using RNA interference
      in mouse embryos.
AB  - Differential gene regulation integrated in time and space drives developmental
      programs during embryogenesis. To understand how the program of gastrulation is
      regulated by Wnt/beta-catenin signaling, we have used genome-wide expression
      profiling of conditional beta-catenin mutant embryos. Known Wnt/beta-catenin
      target genes, known components of other signaling pathways, as well as a number
      of uncharacterized genes were downregulated in these mutants. To further narrow
      down the set of differentially expressed genes, we used whole-mount in situ
      screening to associate gene expression with putative domains of Wnt activity.
      Several potential novel target genes were identified by this means and two, Grsf1
      and Fragilis2, were functionally analyzed by RNA interference (RNAi) in
      completely embryonic stem (ES) cell-derived embryos. We show that the gene
      encoding the RNA-binding factor Grsf1 is important for axial elongation,
      mid/hindbrain development and axial mesoderm specification, and that Fragilis2,
      encoding a transmembrane protein, regulates epithelialization of the somites and
      paraxial mesoderm formation. Intriguingly, the knock-down phenotypes recapitulate
      several aspects of Wnt pathway mutants, suggesting that these genes are
      components of the downstream Wnt response. This functional genomic approach
      allows the rapid identification of functionally important components of embryonic
      development from large datasets of putative targets.

PMID- 15857915
TI  - Multiple roles of the F-box protein Slimb in Drosophila egg chamber development.
AB  - Substrate-specific degradation of proteins by the ubiquitin-proteasome pathway is
      a precise mechanism that controls the abundance of key cell regulators. SCF
      complexes are a family of E3 ubiquitin ligases that target specific proteins for
      destruction at the 26S-proteasome. These complexes are composed of three constant
      polypeptides--Skp1, Cullin1/3 and Roc1/Rbx1--and a fourth variable adapter, the F
      box protein. Slimb (Slmb) is a Drosophila F-Box protein that fulfills several
      roles in development and cell physiology. We analyzed its participation in egg
      chamber development and found that slmb is required in both the follicle cells
      and the germline at different stages of oogenesis. We observed that in slmb
      somatic clones, morphogenesis of the germarium and encapsulation of the cyst were
      altered, giving rise to egg chambers with extra germline cells and two oocytes.
      Furthermore, in slmb somatic clones, we observed ectopic Fasciclin 3 expression,
      suggesting a delay in follicle cell differentiation, which correlated with the
      occurrence of ectopic polar cells, lack of interfollicular stalks and
      mislocalization of the oocyte. Later in oogenesis, Slmb was required in somatic
      cells to specify the position, size and morphology of dorsal appendages. Mild
      overactivation of the Dpp pathway caused similar phenotypes that could be
      antagonized by simultaneous overexpression of Slmb, suggesting that Slmb might
      normally downregulate the Dpp pathway in follicle cells. Indeed, ectopic
      expression of a dad-LacZ enhancer trap revealed that the Dpp pathway was
      upregulated in slmb somatic clones and, consistent with this, ectopic
      accumulation of the co-Smad protein, Medea, was recorded. By analyzing slmb
      germline clones, we found that loss of Slmb provoked a reduction in E2f2 and Dp
      levels, which correlated with misregulation of mitotic cycles during cyst
      formation, abnormal nurse cell endoreplication and impairment of dumping of the
      nurse cell content into the oocyte.

PMID- 15857916
TI  - The Drosophila lymph gland as a developmental model of hematopoiesis.
AB  - Drosophila hematopoiesis occurs in a specialized organ called the lymph gland. In
      this systematic analysis of lymph gland structure and gene expression, we define
      the developmental steps in the maturation of blood cells (hemocytes) from their
      precursors. In particular, distinct zones of hemocyte maturation, signaling and
      proliferation in the lymph gland during hematopoietic progression are described.
      Different stages of hemocyte development have been classified according to marker
      expression and placed within developmental niches: a medullary zone for quiescent
      prohemocytes, a cortical zone for maturing hemocytes and a zone called the
      posterior signaling center for specialized signaling hemocytes. This establishes
      a framework for the identification of Drosophila blood cells, at various stages
      of maturation, and provides a genetic basis for spatial and temporal events that
      govern hemocyte development. The cellular events identified in this analysis
      further establish Drosophila as a model system for hematopoiesis.

PMID- 15857917
TI  - Staggered cell-intrinsic timing of ath5 expression underlies the wave of ganglion
      cell neurogenesis in the zebrafish retina.
AB  - In the developing nervous system, progenitor cells must decide when to withdraw
      from the cell cycle and commence differentiation. There is considerable debate
      whether cell-extrinsic or cell-intrinsic factors are most important for
      triggering this switch. In the vertebrate retina, initiation of neurogenesis has
      recently been explained by a 'sequential-induction' model--signals from newly
      differentiated neurons are thought to trigger neurogenesis in adjacent
      progenitors, creating a wave of neurogenesis that spreads across the retina in a
      stereotypical manner. We show here, however, that the wave of neurogenesis in the
      zebrafish retina can emerge through the independent action of progenitor cells-
      progenitors in different parts of the retina appear pre-specified to initiate
      neurogenesis at different times. We provide evidence that midline Sonic hedgehog
      signals, acting before the onset of neurogenesis, are part of the mechanism that
      sets the neurogenic timer in these cells. Our results highlight the importance of
      intrinsic factors for triggering neurogenesis, but they also suggest that early
      signals can modulate these intrinsic factors to influence the timing of
      neurogenesis many cell cycles later, thereby potentially coordinating axial
      patterning with control of neuron number and cell fate.

PMID- 15857918
TI  - Novel brain wiring functions for classical morphogens: a role as graded
      positional cues in axon guidance.
AB  - During embryonic development, morphogens act as graded positional cues to dictate
      cell fate specification and tissue patterning. Recent findings indicate that
      morphogen gradients also serve to guide axonal pathfinding during development of
      the nervous system. These findings challenge our previous notions about
      morphogens and axon guidance molecules, and suggest that these proteins, rather
      than having sharply divergent functions, act more globally to provide graded
      positional information that can be interpreted by responding cells either to
      specify cell fate or to direct axonal pathfinding. This review presents the roles
      identified for members of three prominent morphogen families--the Hedgehog, Wnt
      and TGFbeta/BMP families--in axon guidance, and discusses potential implications
      for the molecular mechanisms underlying their guidance functions.

PMID- 15857919
TI  - Regulating renal drug elimination?

PMID- 15857920
TI  - Asymmetrical dimethylarginine plasma concentrations are related to basal nitric
      oxide release but not endothelium-dependent vasodilation of resistance arteries
      in peritoneal dialysis patients.
AB  - Vascular dysfunction in chronic renal failure may be linked to reduced nitric
      oxide (NO) bioactivity and increased circulating concentrations of the endogenous
      NO synthase inhibitor asymmetrical dimethyl L-arginine (ADMA). The association
      between ADMA and basal endothelial NO release and endothelium-dependent
      vasodilation in resistance arteries of chronic renal failure patients is unknown.
      Forearm blood flow responses to the endothelium-dependent vasodilator
      acetylcholine, the endothelium-independent vasodilator nitroglycerine, and the
      endothelium-dependent vasoconstrictor N(G)-monomethyl-L-arginine (L-NMMA) were
      assessed in 37 peritoneal dialysis patients. L-arginine and ADMA plasma
      concentrations were measured by HPLC. ADMA (mean +/- SEM: 0.68 +/- 0.02
      micromol/L) was associated with basal forearm blood flow (r = -0.33; P < 0.05)
      and L-NMMA induced vasoconstriction (r = -0.55; P < 0.0005), but not with dilator
      effects of acetylcholine or nitroglycerine. L-arginine (68 +/- 3 micromol/L)
      tended to correlate with acetylcholine-induced vasodilation (r = 0.32; P = 0.05)
      but was not associated with other parameters. ADMA is related to basal but not to
      acetylcholine-stimulated NO bioactivity in patients on peritoneal dialysis.
      Impaired endothelium-dependent vasodilation found in chronic renal failure is not
      explained by elevated circulating NO synthase inhibitors in renal failure.

PMID- 15857921
TI  - Impact of cadaveric renal transplantation on survival in patients listed for
      transplantation.
AB  - The aim of this study was to assess the magnitude of the survival benefit of
      renal transplantation compared with dialysis in patients selected for
      transplantation in Scotland. Longitudinal study of survival and mortality risk in
      all adult patients (1732) listed for a first transplant between January 1, 1989,
      and December 31, 1989, in Scotland. A time-dependent Cox regression analysis
      adjusted for comorbidity, sociodemographic and geographic factors, primary renal
      disease, time on dialysis, and year of listing compared the risk of death for
      patients receiving a first cadaveric transplant versus all patients on dialysis
      listed for transplantation. After adjustment for the covariates, the relative
      risk (RR) of death during the first 30 days after transplantation was 1.35 (95%
      confidence interval [CI], 0.63 to 2.86) compared with patients on dialysis (RR =
      1). The long-term RR (at 18 mo) for the transplant recipients was 0.18 (95% CI,
      0.08 to 0.42) when compared with patients on dialysis (RR = 1). This lower long
      term risk of death was present in all patients undergoing transplantation,
      irrespective of their age group or primary renal disease. Similar results were
      seen when survival with a transplant was censored for graft failure. The
      projected life expectancy with a transplant was 17.19 yr compared with only 5.84
      yr on dialysis. Despite an initial higher risk of death, long-term survival for
      patients who undergo transplantation is significantly better compared with
      patients who are listed but remain on dialysis. A successful transplant triples
      the life expectancy of a listed renal failure patient.

PMID- 15857922
TI  - Prediction of acute renal allograft rejection by urinary monokine induced by IFN
      gamma (MIG).
AB  - Early diagnosis of acute allograft rejection (AR) is still decisive for long-term
      renal allograft survival. The aim of this study was to define the role of the
      chemokine monokine induced by IFN-gamma (MIG) (CXCL9) and IFN-gamma-inducible
      protein 10 (IP-10) (CXCL10) as early markers of AR in renal transplantation
      (NTX). In a prospective study, 69 de novo renal transplant recipients were
      monitored and urine samples were collected after NTX for a median of 29 d. In pH
      adjusted urine, MIG and IP-10 were determined by modified ELISA. AR was
      clinically diagnosed in 15 of 69 recipients and confirmed by biopsy in 14 of 15
      AR patients (Banff classification). Corresponding to CXCR3-positive infiltrates
      in renal tissue, urinary MIG was elevated in 14 of 15 AR patients with a median
      of 2809 pg/ml (quartile 25% and 75% = 870 and 13,000; n = 15), being
      significantly (P < 0.0001) different from both nonrejecting allograft patients
      (NO-AR) (median, 25%, and 75%: 96, 1.0, and 161, n = 54) and healthy controls
      (median, 25%, and 75%: 144, 19, and 208, n = 13). Urinary MIG predicted AR with a
      sensitivity of 93% and a specificity of 89%. In AR and NO-AR groups, MIG values
      correlated well with IP-10 (P < 0.001). MIG values indicated both imminent
      rejection and response to successful antirejection therapy. MIG was not related
      to intercurrent infections or other causes for impairment of renal function. In a
      multivariate analysis, MIG correlated best (P < 0.001) with AR from all AR
      associated parameters. In conclusion, urinary MIG serves as a very sensitive and
      specific predictor for AR, mirrors response to antirejection therapy, and thus
      may contribute to improved long-term renal allograft survival.

PMID- 15857923
TI  - Effect of ultrafiltration on thermal variables, skin temperature, skin blood
      flow, and energy expenditure during ultrapure hemodialysis.
AB  - The cause of the increase in core temperature (CT) during hemodialysis (HD) is
      still under debate. It has been suggested that peripheral vasoconstriction as a
      result of hypovolemia, leading to a reduced dissipation of heat from the skin, is
      the main cause of this increase in CT. If so, then it would be expected that
      extracorporeal heat flow (Jex) needed to maintain a stable CT (isothermic; T
      control = 0, no change in CT) is largely different between body temperature
      control HD combined with ultrafiltration (UF) and body temperature control HD
      without UF (isovolemic). Consequently, significant differences in DeltaCT would
      be expected between isovolemic HD and HD combined with UF at zero Jex
      (thermoneutral; E-control = 0, no supply or removal of thermal energy to and from
      the extracorporeal circulation). During the latter treatment, the CT is expected
      to increase. In this study, changes in thermal variables (CT and Jex), skin blood
      flow, energy expenditure, and cytokines (TNF-alpha, IL-1 receptor antagonist, and
      IL-6) were compared in 13 patients, each undergoing body temperature control (T
      control = 0) HD without and with UF and energy-neutral (E-control = 0) HD without
      and with UF. CT increased equally during energy-neutral treatments, with (0.32 +/
      0.16 degrees C; P = 0.000) and without (0.27 +/- 0.29 degrees C; P = 0.006) UF.
      In body temperature control treatments, the relationship between Jex and UF
      tended to be significant (r = -0.51; P = 0.07); however, there was no significant
      difference in cooling requirements regardless of whether treatments were done
      without (-17.9 +/- 9.3W) or with UF (-17.8 +/- 13.27W). Changes in energy
      expenditure did not differ among the four treatment modes. There were no
      significant differences in pre- and postdialysis levels of cytokines within or
      between treatments. Although fluid removal has an effect on thermal variables, no
      single mechanism seems to be responsible for the increased heat accumulation
      during HD.

PMID- 15857924
TI  - Intercellular adhesion molecule-1 deficiency is protective against nephropathy in
      type 2 diabetic db/db mice.
AB  - Diabetic nephropathy is a leading cause of end-stage renal failure and is a
      growing concern given the increasing incidence of type 2 diabetes. Diabetic
      nephropathy is associated with progressive kidney macrophage accumulation and
      experimental studies suggest that intercellular adhesion molecule (ICAM)-1
      facilitates kidney macrophage recruitment during type 1 diabetes. To ascertain
      the importance of ICAM-1 in promoting type 2 diabetic nephropathy, the
      development of renal injury in ICAM-1 intact and deficient db/db mice with
      equivalent hyperglycemia and obesity between ages 2 and 8 mo was examined and
      compared with results with normal db/+ mice. Increases in albuminuria (11-fold),
      glomerular leukocytes (10-fold), and interstitial leukocytes (three-fold)
      consisting of predominantly CD68+ macrophages were identified at 8 mo in diabetic
      db/db mice compared with nondiabetic db/+ mice. In comparison to db/db mice, ICAM
      1-deficient db/db mice had marked reductions in albuminuria at 6 mo (77% downward
      arrow) and 8 mo (85% downward arrow). There was also a significant decrease in
      glomerular (63% downward arrow) and interstitial (83% downward arrow) leukocytes
      in ICAM-1-deficient db/db mice, which were associated with reduced glomerular
      hypertrophy and hypercellularity and tubular damage. The development of renal
      fibrosis (expression of TGF-beta1, collagen IV, and interstitial alpha-smooth
      muscle actin) was also strikingly attenuated in the ICAM-1-deficient db/db mice.
      Additional in vitro studies showed that macrophage activation by high glucose or
      advanced glycation end products could promote ICAM-1 expression on tubular cells
      and macrophage production of active TGF-beta1. Thus, ICAM-1 appears to be a
      critical promoter of nephropathy in mouse type 2 diabetes by facilitating kidney
      macrophage recruitment.

PMID- 15857925
TI  - Effects of anemia and left ventricular hypertrophy on cardiovascular disease in
      patients with chronic kidney disease.
AB  - Left ventricular hypertrophy (LVH) and anemia are highly prevalent in moderate
      chronic kidney disease (CKD). Because anemia may potentiate the adverse effects
      of LVH on cardiovascular outcomes, the effect of both anemia and LVH on outcomes
      in CKD was examined. Data from four community-based longitudinal studies were
      pooled: Atherosclerosis Risk in Communities Study, Cardiovascular Health Study,
      Framingham Heart Study, and Framingham Offspring Study. Serum creatinine levels
      were calibrated indirectly across studies, and GFR was estimated using the
      Modification of Diet in Renal Disease equation. CKD was defined as GFR between 15
      and 60 ml/min per 1.73 m(2). LVH was based on electrocardiogram criteria. Anemia
      was defined as hematocrit <36% in women and 39% in men. The primary outcome was a
      composite of myocardial infarction, stroke, and death; a secondary cardiac
      outcome included only myocardial infarction and fatal coronary heart disease.
      Among 2423 patients with CKD, 96% had electrocardiogram and anemia data. Median
      follow-up was 102 mo. In adjusted analysis, LVH was associated with increased
      risk for composite and cardiac outcomes (hazard ratio [HR], 1.67 [95% confidence
      interval (CI), 1.34 to 2.07] and 1.62 [95% CI, 1.18 to 2.24], respectively),
      whereas anemia was associated with increased risk for the only composite outcome
      (HR, 1.51 [95% CI, 1.27 to 1.81]). The combination of anemia and LVH was
      associated with an increased risk for both study outcomes compared with
      individuals with neither risk factor (HR, 4.15 [95% CI, 2.62 to 6.56] and 3.92
      [95% CI, 2.05 to 7.48]; P = 0.02 and 0.01 for interaction term, respectively).
      The combination of anemia and LVH in CKD identifies a high-risk population.

PMID- 15857927
TI  - LPS receptor (CD14): a receptor for phagocytosis of Alzheimer's amyloid peptide.
AB  - The amyloid beta peptide 42 (Abeta(42)) plays a key role in neurotoxicity in
      Alzheimer's disease. Mononuclear phagocytes, i.e. microglia, have the potential
      to clear Abeta by phagocytosis. Recently, the lipopolysaccharide (LPS) receptor
      CD14 was shown to mediate phagocytosis of bacterial components and furthermore to
      contribute to neuroinflammation in Alzheimer's disease. Here, we investigated
      whether this key innate immunity receptor can interact with Abeta(42) and mediate
      phagocytosis of this peptide. Using flow cytometry, confocal microscopy and two
      photon fluorescence lifetime imaging (FLIM) combined with fluorescence resonance
      energy transfer (FRET), we demonstrated a direct molecular interaction in the
      range of a few nanometers between Abeta(42) and CD14 in human CD14-transfected
      Chinese hamster ovary cells. Investigations using cells that were genetically
      deficient for this receptor showed that in <30 minutes exogenous Abeta(42) added
      to cultured primary microglial cells was phagocytosed into the cytoplasmic
      compartment in a CD14-dependent manner. This phagocytosis occurred at Abeta(42)
      concentration ranges that were considerably lower than the threshold to activate
      a cellular inflammatory reaction. In contrast, there was no association of CD14
      to microglial internalization of microbeads. In complementary clinical
      experiments, we detected a pronounced CD14 immunoreactivity on parenchymal
      microglia spatially correlated to characteristic Alzheimer's disease lesion sites
      in brain sections of Alzheimer's disease patients but not in brain sections of
      control subjects. By showing a close interaction between CD14 and Abeta(42),
      demonstrating a direct role of CD14 in Abeta(42) phagocytosis, and detecting CD14
      specific staining in brains of Alzheimer's disease patients, our results indicate
      a role of the LPS receptor in the pathophysiology of Alzheimer's disease, which
      could be of therapeutic relevance.

PMID- 15857928
TI  - Attentional responses to unattended stimuli in human parietal cortex.
AB  - Right-sided parietal lesions lead to lateralized attentional deficits which are
      most prominent with bilateral stimulation. We determined how an irrelevant
      stimulus in the unattended hemifield alters attentional responses in parietal
      cortex during unilateral orienting. A trial consisted of a central spatial cue, a
      delay and a test phase during which a grating was presented at 9 degrees
      eccentricity. Subjects had to discriminate the orientation of the grating. The
      unattended hemifield was either empty or contained a second, irrelevant grating.
      We carried out a series of functional MRI (fMRI) studies in 35 healthy volunteers
      (13 men and 22 women, aged between 19 and 30 years) as well as a behavioural and
      structural lesion mapping study in 17 right-hemispheric lesion patients, 11 of
      whom had neglect. In the patients with but not in those without neglect, the
      addition of a distractor in the unattended hemifield significantly impaired
      performance if attention was directed contralesionally but not if it was directed
      ipsilesionally. In the healthy volunteers, we discerned two functionally distinct
      areas along the posterior-anterior axis of the intraparietal sulcus (IPS). The
      posterior, descending IPS segment in both hemispheres showed attentional
      enhancement of responses during contralateral attentional orienting and was
      unaffected by the presence of an irrelevant stimulus in the ignored hemifield. In
      contrast, the right-sided horizontal IPS segment showed a strong attentional
      response when subjects oriented to a stimulus in the relevant hemifield and an
      irrelevant stimulus was simultaneously present in the ignored hemifield, compared
      with unilateral stimulation. This effect was independent of the direction of
      attention. The symmetrical left-sided horizontal IPS segment showed the highest
      responses under the same circumstances, in combination with a contralateral bias
      during unilateral stimulation conditions. None of the six patients without
      neglect had a lesion of the horizontal IPS segment. In four of the 11 neglect
      patients, the lesion overlapped with the horizontal IPS activity cluster and lay
      in close proximity to it in another four. The remaining three patients had a
      lesion at a distance from the parietal cortex. Our findings reconcile the role of
      the IPS in endogenous attentional control with the clinically significant
      interaction between direction of attention and bilateral stimulation in right
      parietal lesion patients. Functional imaging in neglect patients will be
      necessary to assess IPS function in those cases where the structural lesion
      spares the middle IPS segment.

PMID- 15857929
TI  - Mutation in the Na+ channel subunit SCN1B produces paradoxical changes in
      peripheral nerve excitability.
AB  - To determine the effect of an established mutation of the beta1 subunit of Na(+)
      channels on nerve excitability, studies were undertaken in patients diagnosed
      with generalized epilepsy with febrile seizures plus (GEFS+). Multiple nerve
      excitability measurements were used to investigate the membrane properties of
      sensory and motor axons in five patients (aged 18-55 years) who were currently
      experiencing no seizures and were not on anticonvulsants. There was no history of
      paraesthesiae, fasciculation or cramps to suggest hyperexcitability of peripheral
      nerve axons. The median nerve was stimulated at the wrist, and compound muscle
      action potentials (CMAPs) were recorded from abductor pollicis brevis and the
      antidromic compound sensory nerve action potential (CSAPs) from digit 2. Stimulus
      response behaviour, strength-duration time constant, threshold electrotonus,
      current-threshold relationship and the recovery of excitability following a
      supramaximal conditioning stimulus were recorded using threshold tracking.
      Compared with normal controls (n = 29), the axons of patients were of higher
      threshold. CMAPs and CSAPs were relatively small, although individual values
      remained within the normal ranges. Refractoriness and relative refractory period
      (markers of transient Na(+) channel function) were significantly reduced in GEFS+
      patients with established mutations in SCN1B (P < 0.05), and strength-duration
      time constants (dependent on persistent Na(+) conductances) were reduced. It is
      suggested that, in peripheral nerve axons, the mutation underlying GEFS+ reduces
      the number of functioning Na(+) channels at the node of Ranvier and that this
      rather than any change in gating of individual channels dominates axonal
      excitability in these patients.

PMID- 15857930
TI  - Gene expression profile in the muscles of patients with inflammatory myopathies:
      effect of therapy with IVIg and biological validation of clinically relevant
      genes.
AB  - To explore the biological significance of gene expression in the pathogenesis of
      inflammatory myopathies, we performed microarray experiments followed by real
      time PCR and immunohistochemistry on muscle biopsies obtained before and after
      therapy from patients with dermatomyositis (DM) who improved and patients with
      inclusion body myositis (sIBM) who did not improve after controlled trials with
      three monthly intravenous immunoglobulin (IVIg) infusions. The pretreatment
      biopsies showed high expression of immunoglobulin, adhesion molecules, chemokines
      and cytokine genes in both sIBM and DM (sIBM > DM). In the repeated biopsies of
      DM patients who clinically improved, 2206 genes were downregulated more than 1.5
      fold; in contrast, 1700 of the same genes remained unchanged in sIBM patients who
      did not improve. Genes markedly downregulated in DM, but not sIBM, were
      interleukin 22, Kallmann syndrome 1 (KAL-1), an adhesion molecule shown for the
      first time in muscle, ICAM-1, complement C1q, and several structural protein
      genes. Because mRNA for KAL-1 was selectively upregulated in vitro by
      transforming growth factor (TGF) beta1, a fibrogenic cytokine immunolocalized in
      the endomysial connective tissue of pretreatment DM muscles, the downregulation
      of both TGF-beta and KAL-1 after IVIg only in DM suggests that these molecules
      have a functional role in connective tissue proliferation and fibrosis. The
      improved muscles of DM, but not sIBM, showed upregulation of chemokines CXCL9
      (Mig) and CXCL11, and several immunoglobulin-related genes, suggesting an effect
      on muscle remodelling and regeneration. The results suggest that IVIg modulates
      several immunoregulatory or structural muscle genes, but only a subset of them
      associated with inflammatory mediators, fibrosis and muscle remodelling are
      connected with the clinical response. Gene arrays, when combined with clinical
      assessments, may provide important information in the pathogenesis of
      inflammatory myopathies.

PMID- 15857931
TI  - Spectrum of myopathic findings in 50 patients with the 3243A>G mutation in
      mitochondrial DNA.
AB  - Myopathy is a typical clinical finding among patients with the 3243A>G mutation
      in mitochondrial DNA (mtDNA), but the variability in such findings has not been
      properly established. We have previously determined the prevalence of patients
      with 3243A>G in a defined population in northern Finland and characterized a
      group of patients who represent a good approximation to a population-based
      cohort. We report here on examinations performed on patients belonging to this
      cohort in order to determine the frequency of myopathy and to evaluate the
      clinical, histological, ultrastructural and single fibre mtDNA variability in
      muscle involvement. Fifty patients with 3243A>G underwent a thorough structured
      interview and clinical examination. Muscle histology, ultrastructure and single
      fibre analysis were examined in a subset of patients. A clinical diagnosis of
      myopathy was made in 50% of cases [95% confidence interval (CI), 36-64] and
      abnormalities in muscle histology were found in 72% (95% CI, 55-86). Moderate
      limb weakness leading to functional impairment was the most common myopathic
      sign, but mild weakness, ptosis and external ophthalmoplegia could also be found.
      The presence of intramitochondrial crystals and cytochrome c oxidase (COX)
      negative fibres and variation in mitochondrial size and shape were more common in
      the muscles of the myopathic patients. Longitudinal variations in mutation
      heteroplasmy were examined in single muscle fibres from two severely affected
      patients. Although the total variation in mutation heteroplasmy along four ragged
      red fibres (RRFs) was small, the mutation heteroplasmy in five 10 microm segments
      was clearly lower (median 68%, range 64-74%) than that in the neighbouring
      segments. There were also segments with deviant mutation load in histologically
      normal fibres in one patient. The highest incidence of myopathy was in the fifth
      decade of life, but, apart from age, no other clinical variables such as gender,
      muscle heteroplasmy, physical inactivity or diabetes were associated with an
      increased risk of myopathy. The clinical presentation of myopathy is highly
      variable in patients with 3243A>G.

PMID- 15857932
TI  - The temporopolar cortex plays a pivotal role in temporal lobe seizures.
AB  - We investigated the role of the temporal pole (TP) in 48 consecutive patients
      with drug-refractory temporal lobe epilepsy (TLE). Chronic depth recordings of TP
      cortex activity were used in association with video recording of ictal symptoms
      during 48 spontaneous seizures. In 23 cases (48%, group 1) the TP was involved at
      the onset of the seizure, before or concurrently with the hippocampus. In the
      remaining 25 patients (52%, group 2) the TP was involved 16.4 +/- 13.8 s after
      the hippocampus. A past history of febrile seizures was found in both groups,
      with no statistical difference. Ictal symptoms did not differentiate TP seizures
      from seizures originating in the hippocampus but the first clinical sign occurred
      sooner in group 1 compared with group 2 (respectively 10.56 +/- 9 and 25.7 +/- 19
      s, respectively, P = 0.005). Loss of awareness also occurred sooner in the case
      of TP seizures compared with mesiotemporal lobe (MTL) seizures (22.9 +/- 22.6
      versus 42.2 +/- 18.6 s, P = 0.0002). MRI data analysis showed that hippocampal
      sclerosis was present in both groups of patients, although it was more frequent
      in patients with MTL onset. Anterior temporal white matter changes were found
      ipsilateral to the epileptogenic area and tended to be more frequent in patients
      with TP seizures. All the patients underwent tailored anterior temporal lobectomy
      that included the TP, the hippocampus, the parahippocampal gyrus and the anterior
      part of the lateral temporal cortex. A better postoperative outcome was achieved
      in group 1 compared with group 2 (Engel class 1, 95 and 72% respectively, P =
      0.04). We conclude that the frequent TP involvement at the onset of seizures
      could be a supplementary explanation for some failures of selective
      amygdalohippocampectomy, which should be addressed preferentially to well
      selected patients. Moreover, the involvement of the TP cortex at the onset of the
      seizures is a good predicting factor for postoperative seizure outcome.

PMID- 15857933
TI  - Autosomal dominant congenital fibre type disproportion: a clinicopathological and
      imaging study of a large family.
AB  - Congenital fibre type disproportion (CFTD) is considered a non-progressive or
      slowly progressive muscle disease with relative smallness of type 1 fibres on
      pathological examination. Although generally benign, CFTD has a variable natural
      course and severe progression has been observed in some patients. The
      pathogenesis of the disorder is unknown and many authors consider CFTD a syndrome
      with multiple aetiologies rather than a separate clinical entity. A positive
      family history has been reported in about 40% of cases, but the inheritance
      pattern is not clear. Both autosomal recessive and dominant modes of inheritance
      have been suggested. The present paper describes a large, multigenerational
      kindred that has an inherited myopathy fulfilling the histological criteria of
      CFTD, with autosomal dominant transmission and high penetrance. The clinical
      picture, remarkably similar in all affected family members, started in early
      infancy with mild limb muscle weakness. There was slow progression of symptoms
      into adulthood, with moderate to severe, mainly proximal, muscle weakness without
      loss of ambulation. Muscle biopsy from two affected individuals demonstrated
      predominance of small type 1 muscle fibres without other significant findings.
      Nerve conduction studies were normal and needle electromyography showed a
      myopathic pattern. MRI examination performed on three patients from successive
      generations showed involvement of proximal limb and paraspinal muscles. The
      clinical and pathological homogeneity in the present family, together with the
      lack of additional histological abnormalities after decades of disease
      progression in two affected individuals, supports this being a distinct myopathy
      with fibre type disproportion. Whether the disease in this family can be regarded
      as a form of the congenital myopathy known as CFTD or rather a unique condition
      sharing histological features with CFTD needs further investigation. This is, to
      our knowledge, the largest kindred with muscle fibre type disproportion reported
      to date. Our data confirm autosomal dominant inheritance, and this is the first
      MRI document of this disorder.

PMID- 15857934
TI  - Leptin stimulates the proliferation of human colon cancer cells in vitro but does
      not promote the growth of colon cancer xenografts in nude mice or intestinal
      tumorigenesis in Apc(Min/+) mice.
AB  - BACKGROUND AND AIMS: Leptin, the product of the ob gene, has been suggested to
      increase the risk of colon cancer. However, we have shown that although leptin
      stimulates epithelial cell proliferation it reduces the development of carcinogen
      induced preneoplastic lesions in the rat colon. Here, we explored the effect of
      leptin in vitro on proliferation of human colon cancer cells, and in vivo on the
      growth of HT-29 xenografts in nude mice and the development of intestinal tumours
      in Apc(Min/+) mice. METHODS: Proliferation of HT-29, LoVo, Caco2, and SW 480
      cells was assessed in the absence or presence of leptin (20-500 ng/ml) by 3H
      thymidine incorporation and cell count. Leptin (800 microg/kg/day) or its vehicle
      was delivered for four weeks to nude mice, inoculated with HT-29 cells on day 0,
      and for six weeks to Apc(Min/+) mice. RESULTS: Leptin dose dependently stimulated
      cell DNA synthesis and growth in all cell lines. In nude mice, leptin caused a
      4.3-fold increase in plasma leptin levels compared with pair fed controls. This
      hyperleptinaemia, despite leptin receptor expression in tumours, did not induce
      significant variation in tumour volume or weight. Tumour Ki-67 index was even
      inhibited. In leptin treated Apc(Min/+) mice, a 2.4-fold increase in plasma
      leptin levels did not modify the number, size, or distribution of intestinal
      adenomas compared with pair fed controls. CONCLUSIONS: Leptin acts as a growth
      factor on colon cancer cells in vitro but does not promote tumour growth in vivo
      in the two models tested. These findings do not support a pivotal role for
      hyperleptinaemia in intestinal carcinogenesis.

PMID- 15857935
TI  - Increasing incidence of Barrett's oesophagus in the general population.
AB  - BACKGROUND: Barrett's oesophagus (BO) predisposes to oesophageal adenocarcinoma.
      Epidemiological data suggest that the incidence of BO is rising but it is unclear
      whether this reflects a true rise in incidence of BO or an increase in detection
      secondary to more upper gastrointestinal endoscopies performed. This study aimed
      to examine the changes in BO incidence relative to the number of upper
      gastrointestinal endoscopies performed in the general population. METHODS: We
      conducted a cohort study using the Integrated Primary Care Information database.
      This general practice research database contains the complete and longitudinal
      electronic medical records of more than 500,000 persons. RESULTS: In total, 260
      incident cases of BO were identified during the study period. The incidence of BO
      increased from 14.3/100,000 person years in 1997 (95% confidence interval (CI)
      8.6-22.4) to 23.1/100,000 person years (95% CI 17.2-30.6) in 2002 (r2 = 0.87).
      The number of upper gastrointestinal endoscopies decreased from 7.2/1000 person
      years (95% CI 6.7-7.7) to 5.7/1000 person years (95% CI 5.4-6.1) over the same
      time period. This resulted in an overall increase in detected BO per 1000
      endoscopies from 19.8 (95% CI 12.0-31.0) in 1997 to 40.5 (95% CI 30.0-53.5) in
      2002 (r2 = 0.93). The incidence of adenocarcinoma increased from 1.7/100,000
      person years (95% CI 0.3-5.4) in 1997 to 6.0/100,000 person years (95% CI 3.3
      10.2) in 2002 (r2 = 0.87). CONCLUSION: The incidence of diagnosed BO is
      increasing, independent of the number of upper gastrointestinal endoscopies that
      are being performed. This increase in BO incidence will likely result in a
      further increase in the incidence of oesophageal adenocarcinomas in the near
      future.

PMID- 15857936
TI  - Enhancement of antigen acquisition by dendritic cells and MHC class II-restricted
      epitope presentation to CD4+ T cells using VP22 DNA vaccine vectors that promote
      intercellular spreading following initial transfection.
AB  - Induction of immune responses against microbial antigens using DNA is an
      attractive strategy to mimic the immunity induced by live vaccines. Although DNA
      vaccines are efficacious in murine models, the requirement for multiple
      immunizations using high doses in outbred animals and humans has hindered
      deployment. This requirement is, in part, a result of poor vaccine spreading and
      suboptimal DC transfection efficiency. Incorporation of a signal that directs
      intercellular spreading of a DNA-encoded antigen is proposed to mimic live
      vaccine spreading and increase dendritic cell (DC) presentation. Bovine herpes
      virus 1 tegument protein, BVP22, is capable of trafficking to surrounding cells.
      To test the hypothesis that BVP22 enhances spreading and antigen presentation to
      CD4+ T cells, a DNA construct containing BVP22, fused in-frame to a sequence
      encoding a T cell epitope of Anaplasma marginale, was generated. A construct with
      reversed BVP22 sequence served as a negative control. Immunocytometric analysis
      of transfected primary keratinocytes, human embryonic kidney 293, COS-7, and
      Chinese hamster ovary cells showed that BVP22 enhanced intercellular spreading by
      > or = 150-fold. Flow cytometric analysis of antigen-presenting cells (APCs)
      positively selected from cocultures of transfected cells and APCs showed that 5%
      of test APCs were antigen-positive, compared with 0.6% of control APCs. Antigen
      specific CD4+ T cell proliferation demonstrated that BVP22 enhanced DC antigen
      presentation by > or = 20-fold. This first report of the ability of BVP22 to
      increase DNA-encoded antigen acquisition by DCs and macrophages, with subsequent
      enhancement of major histocompatibility complex class II-restricted CD4+ T cell
      responses, supports incorporating a spreading motif in a DNA vaccine to target
      CD4+ T cell-dependent immunity in outbred animals.

PMID- 15857938
TI  - Bcr-Abl regulates osteopontin transcription via Ras, PI-3K, aPKC, Raf-1, and MEK.
AB  - Chronic myeloid leukemia (CML) is caused by the constitutively active Bcr-Abl
      tyrosine kinase. This fusion protein is generated by the Philadelphia
      translocation t(9;22). CML is a progressive condition that invariably advances
      from a drug-sensitive to a drug-resistant, aggressive, acute leukemia. The
      mechanisms responsible for this progression are largely unknown; however, in many
      cases, progression is accompanied by an increase in Bcr-Abl expression.
      Osteopontin (OPN) expression has been shown to be involved in the progression and
      increased aggression and invasiveness of many solid tumors. Here, we demonstrate
      that OPN expression is induced in a model of leukemia, and we describe the
      identification of specific signaling pathways required for the induction of OPN
      expression by p210 Bcr-Abl. We have determined that high levels of Bcr-Abl
      activate a signaling cascade involving the sequential activation of Ras,
      phosphatidylinositol-3 kinase, atypical protein kinase C, Raf-1, and mitogen
      activated protein kinase kinase, leading to the ultimate expression of OPN. Our
      results suggest that these molecules represent a single pathway and also that
      there is no redundancy in this pathway, as inhibition of any individual component
      results in a block in the induction of OPN. The data presented here define for
      the first time the ability of Bcr-Abl to stimulate the expression of OPN and also
      identify the signaling pathway involved. This may not only prove important in
      understanding the mechanisms of progression of CML but also highlights a pathway
      that may prove significant in many other cases of oncogenesis, where OPN
      expression is implicated.

PMID- 15857937
TI  - Enhanced TLR4 reactivity following injury is mediated by increased p38
      activation.
AB  - Severe injury primes the innate-immune system for increased Toll-like receptor 4
      (TLR4)-induced proinflammatory cytokine production by macrophages. In this study,
      we examined changes in TLR4 signaling pathways in splenic macrophages from burn
      injured or sham mice to determine the molecular mechanism(s) responsible for the
      increased TLR4 responsiveness. Using flow cytometry and specific antibodies, we
      first looked for injury-induced changes in the expression levels of several TLR
      associated signaling molecules. We found similar levels of myeloid
      differentiation primary-response protein 88 (MyD88) and interleukin-1 receptor
      associated kinase-M (IRAK-M) and somewhat lower levels of total p38,
      extracellular signal-regulated kinase (ERK), and stress-activated protein kinase
      (SAPK)/c-jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) in
      burn compared with sham macrophages. However, with the use of antibodies specific
      for the phosphorylated (activated) forms of the three MAPKs, we found that
      macrophages from burn mice showed a twofold increase in purified
      lipopolysaccharide (LPS)-stimulated p38 activation as compared with cells from
      sham mice on days 1 and 7 post-injury, whereas ERK and SAPK/JNK activation was
      increased by burn injury only on day 1. Using the specific p38 inhibitor
      (SB203580), we confirmed that the increase in tumor necrosis factor alpha
      production by LPS-stimulated burn macrophages requires p38 activation. Although
      we demonstrated that injury increases macrophage TLR4 mRNA expression and
      intracellular expression of TLR4-myeloid differentiation protein-2 (MD-2)
      protein, macrophage cell-surface expression of TLR4-MD-2 was not changed by burn
      injury. Our results suggest that the injury-induced increase in TLR4 reactivity
      is mediated, at least in part, by enhanced activation of the p38 signaling
      pathway.

PMID- 15857939
TI  - Lipopolysaccharide stimulation converts vigorously washed dendritic cells (DCs)
      to nonexhausted DCs expressing CD70 and evoking long-lasting type 1 T cell
      responses.
AB  - A great variety of in vitro culture protocols for human monocyte-derived
      dendritic cells (mo-DCs) has been used to generate DCs suitable for use in
      immunotherapy. It is thought that activated DCs undergo one-way differentiation
      into "exhausted" DCs. In the present study, we contrived an in vitro method for
      facilitating expression of CD70 by mature DCs. This was achieved by vigorous
      washing of mo-DCs before exposure to lipopolysaccharide (LPS). Unexpectedly,
      these mature DCs retain expression of some interleukin (IL)-12 family members
      after extended periods and maintain their ability to stimulate type 1 T cell
      responses. In contrast, DCs exposed to IL-4 before LPS stimulation or LPS
      stimulated DCs not exposed to washing stress before activation failed to express
      CD70 and did differentiate into exhausted DCs. It is interesting that DCs
      expressing CD70 (CD70+ DCs) induced interferon-gamma production from purified,
      allogeneic CD8+ T cells through a direct CD27-CD70 interaction. This is evidence
      for a pathway resulting in generation of CD8 T effectors by B7-independent
      mechanisms. These data suggest that exposure of immature DCs to LPS stimulation
      contributes to their terminal differentiation into CD70+ DCs, which have potent
      ability to prolong type 1 T cell responses through alternative pathways.

PMID- 15857940
TI  - Time-course expression of Toll-like receptors 2 and 4 in inflammatory bowel
      disease and homeostatic effect of VIP.
AB  - Toll-like receptor 2 (TLR2) and -4 mediate signals from a great variety of
      bacterial gut products, giving the host a panel of microbe-recognizing receptors.
      Under homeostatic conditions, TLRs act as protective receptors of the intestinal
      epithelium. When homeostasis is disrupted in diseases such as inflammatory bowel
      disease, TLR2 and -4 are deregulated. Our study demonstrates, by using a
      trinitrobenzene sulfonic acid-induced colitis model of Crohn's disease, the
      constitutive expression and the up-regulation of TLR2 and -4 at messenger and
      protein levels in colon extracts, as well as in macrophages, dendritic cells, and
      lymphocytes from mesenteric lymphoid nodes. Vasoactive intestinal peptide (VIP)
      treatment induced a decrease of TLR2 and -4 expressions approaching ethanol
      control levels. Our results suggest that VIP modulation of TLR2 and -4 could be
      explained by two possible mechanisms. The first one would be the secondary
      reduction of TLR2 and -4 caused by the VIP-mediated decrease of inflammatory
      mediators such as interleukin-1beta and interferon-gamma, which synergize with
      bacterial products, contributing to the amplification of TLR presence in the
      intestine. The other possible mechanism would involve a VIP-mediated decrease of
      nuclear factor-kappaB, which would cause a direct down-regulation of TLR
      expression. In summary, the resultant physiological effect is the decrease of
      TLR2 and -4 expressions to homeostatic levels. Our study describes for the first
      time the role of a peptide present in the gut microenvironment as an effective
      modulator of the initial steps of acute inflammation, acting at local and
      systemic levels and leading to the restoration of the homeostasis lost after an
      established inflammatory/autoimmune disease.

PMID- 15857941
TI  - A phagocytic cell line markedly improves survival of infected neutropenic mice.
AB  - Disseminated candidiasis is a frequent infection in neutropenic patients, in whom
      it causes 50% mortality, despite antifungal therapy. As the duration of
      neutropenia is the strongest predictor of survival in neutropenic patients with
      invasive fungal infections, neutrophil transfusions are a logical, therapeutic
      option. However, significant technical barriers have prevented the clinical use
      of neutrophil transfusions. To overcome these barriers, we identified a human
      phagocytic cell line that could be administered to candidemic hosts in lieu of
      freshly harvested neutrophils. HL-60 cells killed Candida albicans in vitro.
      Activation of HL-60 cells with dimethyl sulfoxide and retinoic acid abrogated the
      cells' proliferation and augmented their killing of C. albicans. Administration
      of activated HL-60 cells to candidemic, neutropenic mice significantly improved
      survival (53% vs. 0%). Live HL-60 cells chemotaxed to sites of infection,
      phagocytized C. albicans, and reduced the fungal burden in key target organs.
      Although unactivated HL-60 cells also reduced tissue fungal burden in vivo, they
      did not improve survival as a result of their toxicity in infected mice. In
      contrast, no toxicity as a result of activated HL-60 cells was observed at up to
      2 months of follow-up. To our knowledge, this is the first description of a cell
      line-based immunotherapy for an infectious disease. With further refinements,
      activated HL-60 cells have the potential to overcome the technical barriers to
      neutrophil transfusions.

PMID- 15857942
TI  - Occurrence and molecular analysis of extended-spectrum {beta}-lactamase-producing
      Proteus mirabilis in Hong Kong, 1999-2002.
AB  - OBJECTIVES: A study was conducted to evaluate the occurrence and characterization
      of extended-spectrum beta-lactamases (ESBLs) among blood isolates of Proteus
      mirabilis collected over a 4 year period in Hong Kong. METHODS: Production of
      ESBLs among 99 consecutive and non-duplicate isolates was evaluated by the double
      disc synergy test. The ESBLs were characterized by isoelectric focusing and PCR
      sequencing using specific primers. The epidemiological relationship of the
      isolates was studied by the Dienes test and PFGE. RESULTS: ESBLs were identified
      in 13 isolates, from none in 1999-2000 and up to 18.5% (5/27) in 2001 and 25.8%
      (8/31) in 2002. The ESBL-producing isolates were more resistant to ceftriaxone
      than to ceftazidime, and were more likely than non-ESBL-producers to have
      resistance to ciprofloxacin (76.9% versus 14%) and gentamicin (38.5% versus
      9.3%). The ESBL content included CTX-M-13 (n=8), CTX-M-14 (n=3), SHV-5 (n=2), TEM
      11 (n=1), and an unidentified ESBL with a pI of 7.5. The Dienes test revealed
      that the genetic background in the 99 isolates was highly heterogeneous, with 54
      distinct types among 92 isolates and seven were non-typeable. Among the 13 ESBL
      producing isolates, five different backgrounds, including one cluster (Dienes
      pulsotype A) with nine isolates, were identified by both Dienes test and PFGE,
      thus suggesting both clonal and multi-clonal spread of the CTX-M enzymes.
      CONCLUSIONS: Our findings indicate the emergence of CTX-M enzymes among P.
      mirabilis in Hong Kong. More ESBL screening of this species is required to
      improve their recognition.

PMID- 15857943
TI  - A new approach for treatment of deep skin infections by an ethosomal antibiotic
      preparation: an in vivo study.
AB  - OBJECTIVES: Dermal and subdermal bacterial infections, caused mainly by
      Staphylococcus aureus, are currently treated by systemic antibiotics. The aim of
      the present study was to investigate a new approach to treat deep skin and soft
      tissue bacterial infections by dermal application of erythromycin in an ethosomal
      carrier. METHODS: A model for deep dermal S. aureus infection in mice was
      developed. The efficiency of ethosomal erythromycin applied to the skin-infected
      site was compared with intraperitoneal erythromycin administration and with local
      application of hydroethanolic erythromycin solution. The parameters evaluated
      were the development of dermal wound, histological sections and bacterial count
      of the infected tissue. RESULTS: The in vivo experiments demonstrated a very
      efficient healing of S. aureus-induced deep dermal infections when the mice were
      treated with ethosomal erythromycin. Bacterial counts and histological evaluation
      of the skin treated with ethosomal antibiotic revealed no bacterial growth and
      normal skin structure. On the contrary, no subdermal healing was observed in
      infected animals treated with topical hydroethanolic erythromycin solution. In
      this group, animals developed deep dermal abscesses and the dermal structures
      were destroyed where S. aureus colonies were present. Bacterial counts of the
      infected tissues were 1.06 x 10(7) and 0.27 x 10(7) cfu/g of tissue,
      respectively, on days 7 and 10. CONCLUSIONS: Therapy with ethosomal erythromycin
      applied to the skin of S. aureus-infected mice was as effective as systemically
      administered erythromycin, suggesting a new possibility to treat deep dermal
      infections by local application of antibiotic in ethosomal carrier.

PMID- 15857944
TI  - Comparative evaluation of tigecycline and vancomycin, with and without
      rifampicin, in the treatment of methicillin-resistant Staphylococcus aureus
      experimental osteomyelitis in a rabbit model.
AB  - OBJECTIVES: Staphylococcus aureus is the most common organism isolated in
      osteomyelitis. Methicillin-resistant S. aureus (MRSA) infections are particularly
      difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with
      and without rifampicin in a rabbit model of MRSA osteomyelitis. METHODS: A 28 day
      antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice
      daily), with and without oral rifampicin (40 mg/kg twice daily); or subcutaneous
      administration of vancomycin (30 mg/kg twice daily), with and without oral
      rifampicin (40 mg/kg twice daily) were compared. Osteomyelitis was induced with
      an intramedullary injection of 10(6) colony-forming units of MRSA. Infected
      rabbits were randomly divided into six groups: tigecycline, tigecycline with oral
      rifampicin, vancomycin, vancomycin with oral rifampicin, and no treatment control
      and tigecycline bone penetration groups. Treatment began 2 weeks after infection.
      After 4 weeks of therapy, the rabbits were left untreated for 2 weeks. Rabbits
      were then euthanized, and the tibias were harvested. The bones were cultured, and
      bacterial counts of MRSA were performed. RESULTS: Rabbits that received
      tigecycline and oral rifampicin therapy (n=14) showed a 100% infection clearance.
      Rabbits treated with tigecycline (n=10) showed a 90% clearance. Rabbits treated
      with vancomycin and oral rifampicin (n=10) also showed a 90% clearance. Rabbits
      treated with vancomycin (n=11) showed an 81.8% clearance. Untreated controls
      (n=15) demonstrated only a 26% clearance. For the tigecycline bone penetration
      group, the bone concentrations of tigecycline in the infected tibia were
      significantly higher than the non-infected ones. CONCLUSIONS: Tigecycline may be
      an effective alternative to vancomycin in the treatment of MRSA osteomyelitis.

PMID- 15857945
TI  - Characterization of the discriminative stimulus effects of the neuroactive
      steroid pregnanolone in DBA/2J and C57BL/6J inbred mice.
AB  - Neurosteroids represent a class of endogenous compounds that exert rapid,
      nongenomic effects through neurotransmitter receptor systems such as GABA(A). Two
      neurosteroids, allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) and
      pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one), possess anxiolytic and
      sedative properties and show substitution for ethanol, benzodiazepines, and
      barbiturates in drug discrimination assays. This study aimed to examine the
      effects of strain and sex on the discriminative stimulus effects of pregnanolone.
      Twelve male and female DBA/2J mice and 12 male and female C57BL/6J mice were
      trained to discriminate 10 mg/kg pregnanolone from saline. The male C57BL/6J mice
      had to be removed from the study due to increased seizures apparently associated
      with the chronic intermittent pregnanolone administration used in drug
      discrimination. GABA(A)-positive modulators, neuroactive steroids, N-methyl-d
      aspartate (NMDA) antagonists, and 5-hydroxytryptamine (5-HT)(3) agonists were
      tested for pregnanolone substitution. In DBA/2J and C57BL/6J mice, a
      benzodiazepine, barbiturate, and GABAergic neuroactive steroids all substituted
      for the stimulus effects of pregnanolone. NMDA antagonists, 5-HT(3) agonists, and
      zolpidem failed to substitute for pregnanolone's discriminative stimulus in
      either sex or strain. Pentobarbital and midazolam were more potent in producing
      pregnanolone-like discriminative stimulus effects in DBA/2J mice. Differences in
      sensitivities to neurosteroids between the two strains were not evident. These
      results provide a comprehensive look at pregnanolone's discriminative stimulus
      effects in two commonly used strains of mice. The present data suggest that many
      of the previously documented neurosteroid-induced behavioral differences between
      the DBA/2J and C57BL/6J are acute effects and are not apparent in a drug
      discrimination procedure.

PMID- 15857946
TI  - Tranilast prevents the progression of experimental diabetic nephropathy through
      suppression of enhanced extracellular matrix gene expression.
AB  - The present study was performed to investigate the effects of the antiallergic
      drug tranilast on the development of diabetic nephropathy in streptozotocin (50
      mg/kg)-induced diabetic spontaneously hypertensive rats (SHR). Diabetic SHR were
      given standard chow or chow containing tranilast at a dose of 1400 mg/kg for 24
      weeks. The effects of tranilast on urinary albumin excretion, mesangial
      expansion, expression of transforming growth factor-beta (TGF-beta) and type I
      collagen mRNAs, number of anionic sites on the glomerular basement membrane
      (GBM), and urinary TGF-beta and 8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion
      were assessed. Tranilast did not affect the blood glucose concentration or blood
      pressure in diabetic SHR. Urinary albumin excretion rate and creatinine clearance
      were markedly increased in diabetic SHR. Tranilast treatment decreased
      albuminuria and hyperfiltration. Tranilast inhibited the diabetes-induced
      expansion of mesangial and tuft areas, as well as the increase in urinary TGF
      beta and 8-OHdG excretion, loss of anionic sites of GBM, and overexpression of
      TGF-beta as determined immunohistochemically. The levels of TGF-beta and type I
      collagen mRNA expression were increased in the renal cortex in untreated diabetic
      SHR at 24 weeks, as determined by real-time quantitative polymerase chain
      reaction. Tranilast treatment inhibited the up-regulation of TGF-beta and type I
      collagen mRNA expression by 65 and 36%, respectively, in diabetic SHR. In
      conclusion, tranilast decreased albuminuria by suppressing glomerular
      hyperfiltration, mesangial expansion, and loss of the charge barrier via
      regulation of extracellular matrix gene expression and oxidative stress.
      Tranilast may be clinically useful in the treatment of diabetic nephropathy.

PMID- 15857947
TI  - Zinc activates TREK-2 potassium channel activity.
AB  - TWIK-related K(+) channel (TREK)-2 is thought to contribute to setting the
      resting membrane potential and to tuning action potential properties. In the
      present study, the effects of divalent metal ions (Ba(2+), Co(2+), Ni(2+),
      Pb(2+), and Zn(2+)) were examined on TREK-2 expressed in Xenopus oocytes using
      the two-electrode voltage clamping technique. Pb(2+) inhibited TREK channel
      activity (IC(50) = 15.6 microM), whereas Zn(2+) enhanced it in a dose-dependent
      manner (EC(50) = 87.1 microM). Ba(2+) slightly inhibited TREK currents but only
      at high concentrations. Co(2+) and Ni(2+) had no significant effect. The
      structural element(s) contributing to the zinc enhancement effect were studied
      using a series of chimeras consisting of Zn(2+)-activated TREK-2 and Zn(2+)
      inhibited TWIK-related acid-sensing K(+) channel-3. The structural elements were
      localized to the first pore and the preceding extracellular loop of TREK-2, in
      which multiple residues, including His121, His156, Asp158, and Asn177, are likely
      to be involved in the zinc activation effect. Stimulation by Zn(2+) may be used
      as a criterion of TREK-2, distinguishing it from other two-pore K(+) channels.

PMID- 15857948
TI  - Phenoxybenzamine and benextramine, but not 4-diphenylacetoxy-N-[2
      chloroethyl]piperidine hydrochloride, display irreversible noncompetitive
      antagonism at G protein-coupled receptors.
AB  - Many irreversible antagonists have been shown to inactivate G protein-coupled
      receptors (GPCRs) and used to study agonists and spare receptors. Presumably,
      they bind to primary (agonist) binding sites on the GPCR, although noncompetitive
      mechanisms of antagonism have been demonstrated but not thoroughly investigated.
      We studied noncompetitive antagonism by phenoxybenzamine and benextramine at
      alpha(2A)-adrenoceptors in stably transfected Chinese hamster ovary cells,
      benextramine and 4-diphenylacetoxy-N-[2-chloroethyl]piperidine hydrochloride (4
      DAMP mustard) at endogenous muscarinic acetylcholine (mACh) receptors in human
      neuroblastoma SH-SY5Y cells, and benextramine at serotonin 5-HT(2A) receptors in
      stably transfected SH-SY5Y cells. Primary binding sites were protected by
      reversible competitive antagonists during pretreatment with irreversible
      antagonists. We conducted appropriate radioligand binding assays by measuring
      remaining primary binding sites and agonist affinity, functional assays to
      evaluate agonist-induced responses, and constitutive guanosine 5'-O-(3
      [(35)S]thio)triphosphate ([(35)S]GTPgammaS)-Galpha(o) binding assays to determine
      remaining G protein activity. Phenoxybenzamine (100 microM; 20 min) and
      benextramine (10 or 100 microM; 20 min) at alpha(2A)-adrenoceptors, but not 4
      DAMP mustard (100 nM; 120 min) at mACh receptors, displayed irreversible
      noncompetitive antagonism in addition to their known irreversible competitive
      antagonism. Although agonist binding affinity is not influenced, signal
      transduction is modulated in a G protein-dependent manner via allotopic
      interactions. Benextramine noncompetitively inhibits agonist-induced responses at
      three different GPCR types (alpha(2A), mACh, and 5-HT(2A) receptors) that signal
      via three families of G proteins (G(i/o), G(s), and G(q/11)). We conclude that,
      where irreversible antagonists are utilized to study drug-receptor interaction
      mechanisms, the presence of significant irreversible noncompetitive antagonism
      may influence the interpretation of results under the experimental conditions
      used.

PMID- 15857949
TI  - Methotrexate preconditioning allows sufficient engraftment to confer drug
      resistance in mice transplanted with marrow expressing drug-resistant
      dihydrofolate reductase activity.
AB  - Methotrexate (MTX) is an effective antitumor agent that has been demonstrated to
      be particularly useful in the treatment of hematopoietic neoplasms but causes
      substantial hematologic and gastrointestinal toxicity. We previously demonstrated
      that transplantation with transgenic marrow expressing drug-resistant
      dihydrofolate reductase (DHFR) into animals preconditioned by irradiation
      substantially protected recipient mice from the toxic side effects of
      methotrexate administration. Here we test the use of methotrexate itself as a
      preconditioning agent for engraftment of drug-resistant transgenic marrow,
      subsequently conferring drug resistance upon recipient animals. Administration of
      methotrexate beginning 1 or 2 weeks prior to or on the same day as
      transplantation with drug-resistant DHFR transgenic marrow did not allow
      sufficient engraftment to confer drug resistance to most unirradiated recipients.
      A small number of animals were curiously protected from lethal MTX toxicity but
      exhibited extremely low hematocrits and were not engrafted with stem cells, as
      indicated by low engraftment levels assessed in secondary transplant recipients.
      However, we subsequently found that MTX preconditioning allowed sufficient
      engraftment of DHFR transgenic marrow to confer drug resistance if MTX
      administration was withdrawn at the time of bone marrow transplantation (BMT) and
      withheld until 2 weeks post-transplant. Quantitative molecular analysis of
      primary and secondary recipients indicated a stem cell engraftment level of
      approximately 1%, consistent with previous studies demonstrating that a low level
      of DHFR transgenic cell engraftment was sufficient to confer drug resistance in
      recipient animals. We conclude that MTX can be used as a preconditioning agent
      for subsequent engraftment of hematopoietic stem cells, in this case conferring
      resistance to MTX.

PMID- 15857950
TI  - Altruistic punishment and the origin of cooperation.
AB  - How did human cooperation evolve? Recent evidence shows that many people are
      willing to engage in altruistic punishment, voluntarily paying a cost to punish
      noncooperators. Although this behavior helps to explain how cooperation can
      persist, it creates an important puzzle. If altruistic punishment provides
      benefits to nonpunishers and is costly to punishers, then how could it evolve?
      Drawing on recent insights from voluntary public goods games, I present a simple
      evolutionary model in which altruistic punishers can enter and will always come
      to dominate a population of contributors, defectors, and nonparticipants. The
      model suggests that the cycle of strategies in voluntary public goods games does
      not persist in the presence of punishment strategies. It also suggests that
      punishment can only enforce payoff-improving strategies, contrary to a widely
      cited "folk theorem" result that suggests that punishment can allow the evolution
      of any strategy.

PMID- 15857951
TI  - A single intermolecular contact mediates intramolecular stabilization of both RNA
      and protein.
AB  - An arginine-rich peptide from the Jembrana disease virus (JDV) Tat protein is a
      structural "chameleon" that binds bovine immunodeficiency virus (BIV) or HIV TAR
      RNAs in two different binding modes, with an affinity for BIV TAR even higher
      than the cognate BIV peptide. We determined the NMR structure of the JDV Tat-BIV
      TAR high-affinity complex and found that the C-terminal tyrosine in JDV Tat forms
      a network of inter- and intramolecular hydrogen bonding and stacking interactions
      that simultaneously stabilize the beta-hairpin conformation of the peptide and a
      base triple in the RNA. A neighboring histidine also appears to help stabilize
      the peptide conformation. Induced fit binding is recurrent in protein-protein and
      protein-nucleic acid interactions, and the JDV Tat complex demonstrates how high
      affinity can be achieved not only by optimization of the binding interface but
      also by inducing new intramolecular contacts that stabilize each binding partner.
      Comparison to the cognate BIV Tat peptide-TAR complex shows how such a
      costabilization mechanism can evolve with only small changes to the peptide
      sequence. In addition, the bound structure of BIV TAR in the chameleon peptide
      complex is strikingly similar to the bound conformation of HIV TAR, suggesting
      new strategies for the development of HIV TAR binding molecules.

PMID- 15857952
TI  - c-Myc regulates cell size and ploidy but is not essential for postnatal
      proliferation in liver.
AB  - The c-Myc protein is a transcription factor implicated in the regulation of
      multiple biological processes, including cell proliferation, cell growth, and
      apoptosis. In vivo overexpression of c-myc is linked to tumor development in a
      number of mouse models. Here, we show that perinatal inactivation of c-Myc in
      liver causes disorganized organ architecture, decreased hepatocyte size, and cell
      ploidy. Furthermore, c-Myc appears to have distinct roles in proliferation in
      liver. Thus, postnatal hepatocyte proliferation does not require c-Myc, whereas
      it is necessary for liver regeneration in adult mice. These results show novel
      physiological functions of c-myc in liver development and hepatocyte
      proliferation and growth.

PMID- 15857953
TI  - Computer simulation of explicit proton translocation in cytochrome c oxidase: the
      D-pathway.
AB  - Proton translocation in the D-pathway of cytochrome c oxidase has been studied by
      a combination of classical molecular dynamics and the multistate empirical
      valence bond methodology. This approach allows for explicit Grotthuss proton
      hopping between water molecules. According to mutagenesis experiments, the role
      of proton donor/acceptor along the D-pathway is carried by the highly conserved
      residue Glu-242. The present multistate empirical valence bond simulations
      indicate that the protonation/deprotonation state of Glu-242 is strongly coupled
      to the distance of proton propagation in the D-pathway. The proton was seen to
      travel the full length of the D-pathway when Glu-242 was deprotonated; however,
      it was trapped halfway along the path when Glu-242 was protonated. Further
      investigation in terms of both proton dynamical properties and free energy
      calculations for the pathway of proton transport provides evidence for a two-step
      proton transport mechanism in the D-pathway.

PMID- 15857954
TI  - A gating mechanism proposed from a simulation of a human alpha7 nicotinic
      acetylcholine receptor.
AB  - The nicotinic acetylcholine receptor is a well characterized ligand-gated ion
      channel, yet a proper description of the mechanisms involved in gating, opening,
      closing, ligand binding, and desensitization does not exist. Until recently,
      atomic-resolution structural information on the protein was limited, but with the
      production of the x-ray crystal structure of the Lymnea stagnalis acetylcholine
      binding protein and the EM image of the transmembrane domain of the torpedo
      electric ray nicotinic channel, we were provided with a window to examine the
      mechanism by which this channel operates. A 15-ns all-atom simulation of a
      homology model of the homomeric human alpha7 form of the receptor was conducted
      in a solvated palmitoyl-2-oleoyl-sn-glycerol-phosphatidylcholine bilayer and
      examined in detail. The receptor was unliganded. The structure undergoes a twist
      to-close motion that correlates movements of the C loop in the ligand binding
      domain, via the beta10-strand that connects the two, with the 10 degrees rotation
      and inward movement of two nonadjacent subunits. The Cys loop appears to act as a
      stator around which the alpha-helical transmembrane domain can pivot and rotate
      relative to the rigid beta-sheet binding domain. The M2-M3 loop may have a role
      in controlling the extent or kinetics of these relative movements. All of this
      motion, along with essential dynamics analysis, is suggestive of the direction of
      larger motions involved in gating of the channel.

PMID- 15857955
TI  - An anchor site-type defect in human telomerase that disrupts telomere length
      maintenance and cellular immortalization.
AB  - Telomerase-mediated telomeric DNA synthesis is important for eukaryotic cell
      immortality. Telomerase adds tracts of short telomeric repeats to DNA substrates
      using a unique repeat addition form of processivity. It has been proposed that
      repeat addition processivity is partly regulated by a telomerase reverse
      transcriptase (TERT)-dependent anchor site; however, anchor site-mediating
      residues have not been identified in any TERT. We report the characterization of
      an N-terminal human TERT (hTERT) RNA interaction domain 1 (RID1) mutation that
      caused telomerase activity defects consistent with disruption of a template
      proximal anchor site, including reduced processivity on short telomeric primers
      and reduced activity on substrates with nontelomeric 5' sequences, but not on
      primers with nontelomeric G-rich 5' sequences. This mutation was located within a
      subregion of RID1 previously implicated in biological telomerase functions
      unrelated to catalytic activity (N-DAT domain). Other N-DAT and C-terminal DAT (C
      DAT) mutants and a C-terminally tagged hTERT-HA variant were defective in
      elongating short telomeric primers, and catalytic phenotypes of DAT variants were
      partially or completely rescued by increasing concentrations of DNA primers.
      These observations imply that RID1 and the hTERT C terminus contribute to
      telomerase's affinity for its substrate, and that RID1 may form part of the human
      telomerase anchor site.

PMID- 15857956
TI  - A nonribosomal landscape in the nucleolus revealed by the stem cell protein
      nucleostemin.
AB  - Nucleostemin is a p53-interactive cell cycle progression factor that shuttles
      between the nucleolus and nucleoplasm, but it has no known involvement in
      ribosome synthesis. We found the dynamic properties of nucleostemin differed
      strikingly from fibrillarin (a protein directly involved in rRNA processing) both
      in response to rRNA transcription inhibition and in the schedule of reentry into
      daughter nuclei and the nucleolus during late telophase/early G1. Furthermore,
      nucleostemin was excluded from the nucleolar domains in which ribosomes are born-
      the fibrillar centers and dense fibrillar component. Instead it was concentrated
      in rRNA-deficient sites within the nucleolar granular component. This finding
      suggests that the nucleolus may be more subcompartmentalized than previously
      thought. In support of this concept, electron spectroscopic imaging studies of
      the nitrogen and phosphorus distribution in the nucleolar granular component
      revealed regions that are very rich in protein and yet devoid of nucleic acid.
      Together, these results suggest that the ultrastructural texture of the nucleolar
      granular component represents not only ribosomal particles but also RNA-free
      zones populated by proteins or protein complexes that likely serve other
      functions.

PMID- 15857957
TI  - Pushing forces drive the comet-like motility of microtubule arrays in
      Dictyostelium.
AB  - Overexpression of dynein fragments in Dictyostelium induces the movement of the
      entire interphase microtubule array. Centrosomes in these cells circulate through
      the cytoplasm at rates between 0.4 and 2.5 microm/s and are trailed by a comet
      tail like arrangement of the microtubule array. Previous work suggested that
      these cells use a dynein-mediated pulling mechanism to generate this dramatic
      movement and that similar forces are at work to maintain the interphase MTOC
      position in wild-type cells. In the present study, we address the nature of the
      forces used to produce microtubule movement. We have used a laser microbeam to
      sever the connection between the motile centrosomes and trailing microtubules,
      demonstrating that the major force for such motility results from a pushing on
      the microtubules. We eliminate the possibility that microtubule
      assembly/disassembly reactions are significant contributors to this motility and
      suggest that the cell cortex figures prominently in locating force-producing
      molecules. Our findings indicate that interphase microtubules in Dictyostelium
      are subject to both dynein- and kinesin-like forces and that these act in concert
      to maintain centrosome position in the cell and to support the radial character
      of the microtubule network.

PMID- 15857959
TI  - Functional disability, disability transitions, and depressive symptoms in late
      life.
AB  - OBJECTIVE: This article addresses how stable functional disability statuses and
      disability transitions are related to change in depressive symptoms in the
      elderly. METHOD: The authors estimate longitudinal residual change models using
      two waves of data, 1986 and 1992, from the National Institute of Aging
      Established Populations for Epidemiologic Studies of the Elderly, Duke
      University. RESULTS: Both stable disability statuses and transitions in
      disability statuses are significantly related to change in depressive symptoms
      (Center for Epidemiologic Studies depression scale [CES D]). Stable disability
      statuses in strength and mobility, instrumental activities of daily living (IADL)
      items and activities of daily living (ADL) items have increasing effects on
      increment in CES-D scores by the follow-up. The onset of disability has stronger
      effects on change in CES-D scores than recovery. These effects also differ by
      types of transitions in disability statuses. DISCUSSION: The authors discuss
      alternative interpretations of the findings and methodological concerns and also
      suggest avenues for future research.

PMID- 15857958
TI  - Roles of Pdk1p, a fission yeast protein related to phosphoinositide-dependent
      protein kinase, in the regulation of mitosis and cytokinesis.
AB  - Proteins related to the phosphoinositide-dependent protein kinase family have
      been identified in the majority of eukaryotes. Although much is known about
      upstream mechanisms that regulate the PDK1-family of kinases in metazoans, how
      these kinases regulate cell growth and division remains unclear. Here, we
      characterize a fission yeast protein related to members of this family, which we
      have termed Pdk1p. Pdk1p localizes to the spindle pole body and the actomyosin
      ring in early mitotic cells. Cells deleted for pdk1 display multiple defects in
      mitosis and cytokinesis, all of which are exacerbated when the function of
      fission yeast polo kinase, Plo1p, is partially compromised. We conclude that
      Pdk1p functions in concert with Plo1p to regulate multiple processes such as the
      establishment of a bipolar mitotic spindle, transition to anaphase, placement of
      the actomyosin ring and proper execution of cytokinesis. We also present evidence
      that the effects of Pdk1p on cytokinesis are likely mediated via the fission
      yeast anillin-related protein, Mid1p, and the septation initiation network.

PMID- 15857960
TI  - Predictors of HIV-infection in older adults.
AB  - This article is a retrospective case-control study of patients from a Veteran's
      Affairs Medical Center and an urban public hospital. Patients (53) older than 55
      at the time of their HIV diagnosis were age- and gender-matched to 106 HIV
      negative controls. Potential predictors of HIV-infection were abstracted from the
      medical records. HIV-positive patients were more likely to have a history of
      sexually transmitted diseases, have Hepatitis B+, and have significant
      differences in their mean globulin, serum sodium, albumin, and hemoglobin levels.
      The mean albumin to globulin ratio was also statistically, significantly
      different between the HIV-positive patients and the controls. These data suggest
      that for patients older than 55, certain medical history parameters may be useful
      in predicting risk of being HIV-positive. An albumin to globulin ratio < 1.0,
      especially when combined with a history of alcohol abuse or prior sexually
      transmitted disease, should prompt all physicians to screen their older patients
      for HIV.

PMID- 15857961
TI  - Health and living arrangements among older Americans: does marriage matter?
AB  - OBJECTIVE: This research examines how physical and mental health influence living
      arrangements among older Americans and whether these effects differ for married
      and unmarried persons. METHODS: Data came from the Asset and Health Dynamics
      Among the Oldest Old study. These two intervals were pooled, and hierarchical
      multinomial logistic regressions were used to analyze pooled time lags. RESULTS:
      Functional status and cognitive functioning are significantly associated with
      living arrangements among those not married. Health conditions exert no
      significant effects among those married. Given the same functional status,
      unmarried elders are significantly more likely than their married counterparts to
      reside with their children or with others. DISCUSSION: These results underscore
      the critical role of the spouse in influencing living arrangements, providing new
      evidence supporting the assertion that a spouse is the greatest guarantee of
      support in old age and the importance of the marriage institution.

PMID- 15857962
TI  - Stages of change for osteoporosis preventive behaviors: a construct validation
      study.
AB  - OBJECTIVE: This article presents a construct validation study for osteoporosis
      preventive behaviors based on a survey completed by 113 older adults. METHODS:
      Participants were classified using stages of change for osteoporosis preventive
      behaviors according to an algorithm adapted from the Transtheoretical Model of
      health behavior change. RESULTS: One-way analyses of variance and a hierarchical
      regression model indicate that stage of change location is significantly related
      to one's level of knowledge about osteoporosis as well as age, gender, and
      educational attainment. These findings bring support to the validity of the
      instrument. DISCUSSION: Findings from this study indicate that elders' attitudes
      and knowledge about osteoporosis reflect public health messages heralding
      osteoporosis as the disease of the older White women. Significant health care
      expenditures in the nontargeted groups call for a revision in these messages.
      Further applications with more heterogeneous samples are necessary for thorough
      validation and reliability testing of the proposed instrument.

PMID- 15857963
TI  - Changes in Medicare home health care use and practices in rural communities: 1997
      to 2001.
AB  - OBJECTIVE: This research was designed to examine the impact of the interim and
      prospective payment systems on home health agencies and Medicare beneficiaries in
      rural communities. METHODS: Data were collected from two complementary studies:
      (a) fiscal and use data collected from 10 rural agencies in northwest
      Pennsylvania and (b) a statewide survey of rural home health agencies in
      Pennsylvania. RESULTS: The findings show that the implementation of interim and
      prospective payment systems had a profound affect on the home health agencies'
      financial vulnerability, staffing management, and service delivery. As a result,
      Medicare beneficiaries were also affected. The total number of home health visits
      per episode in rural Pennsylvania was 16 visits, whereas the national estimate
      was 22 visits. Physical therapy services increased 8% and occupational therapy
      services increased 1%, whereas visits for other disciplines decreased or remain
      unchanged. DISCUSSION: Future studies are needed to examine the health outcomes
      of beneficiaries in rural communities.

PMID- 15857964
TI  - Preference for long-term care arrangement and its correlates for older Korean
      Americans.
AB  - OBJECTIVE: Care preference is important for both client's satisfaction and
      quality of life in long-term care. This study examines preference for long-term
      care arrangement and its correlates for older Korean Americans. METHODS: Data on
      two disability scenarios of hip fracture and stroke from a cross-section survey
      of 144 older Korean Americans were used to examine preferred care arrangement in
      terms of caregiver and care location, using multinomial logistic regression.
      RESULTS: Respondents expressed stronger preferences for "all informal" or "mixed"
      care arrangement for hip fracture scenario, but they preferred "all formal" care
      arrangement in the stroke scenario. Traditional value significantly decreased the
      odds of choosing "all formal" or "mixed" over "all informal" care arrangement.
      But Medicaid coverage and an independent decision-making style increased the odds
      of choosing "all formal" instead of "all informal" care arrangement. DISCUSSION:
      This study discusses the need for assessment of care preference and culturally
      appropriate long-term care services for minority elders.

PMID- 15857965
TI  - Error parsing in visuomotor pointing reveals independent processing of amplitude
      and direction.
AB  - An experiment investigated systematic pointing errors in horizontal movements
      performed without visual feedback toward 48 targets placed symmetrically around
      two initial hand positions. Our main goal was to provide evidence in favor of the
      hypothesis that amplitude and direction of the movements are planned
      independently on the basis of the hand-target vector (vectorial parametric
      hypothesis, VP). The analysis was carried out mainly at the individual level. By
      screening a number of formal models of the potential error components, we found
      that only models compatible with the VP hypothesis provide an accurate
      description of the error pattern. A quantitative analysis showed that errors are
      explained mostly by a bias in the represented initial hand position (46% of the
      sum of squared errors) and a visuomotor gain bias (26%). Range effect (3%),
      directional biases (3%), and inertia-dependent amplitude modulations (1%) also
      provided significant contributions. The error pattern was incompatible with the
      view that movements are planned by specifying either a final posture or a final
      position. Instead, the results fully supported the view that, at least in the
      horizontal plane, amplitude, and direction of pointing movements are planned
      independently in a hand- or target-centered frame of reference.

PMID- 15857966
TI  - Neural correlates and mechanisms of spatial release from masking: single-unit and
      population responses in the inferior colliculus.
AB  - Spatial release from masking (SRM), a factor in listening in noisy environments,
      is the improvement in auditory signal detection obtained when a signal is
      separated in space from a masker. To study the neural mechanisms of SRM, we
      recorded from single units in the inferior colliculus (IC) of barbiturate
      anesthetized cats, focusing on low-frequency neurons sensitive to interaural time
      differences. The stimulus was a broadband chirp train with a 40-Hz repetition
      rate in continuous broadband noise, and the unit responses were measured for
      several signal and masker (virtual) locations. Masked thresholds (the lowest
      signal-to-noise ratio, SNR, for which the signal could be detected for 75% of the
      stimulus presentations) changed systematically with signal and masker location.
      Single-unit thresholds did not necessarily improve with signal and masker
      separation; instead, they tended to reflect the units' azimuth preference. Both
      how the signal was detected (through a rate increase or decrease) and how the
      noise masked the signal response (suppressive or excitatory masking) changed with
      signal and masker azimuth, consistent with a cross-correlator model of binaural
      processing. However, additional processing, perhaps related to the signal's
      amplitude modulation rate, appeared to influence the units' responses. The
      population masked thresholds (the most sensitive unit's threshold at each signal
      and masker location) did improve with signal and masker separation as a result of
      the variety of azimuth preferences in our unit sample. The population thresholds
      were similar to human behavioral thresholds in both SNR value and shape,
      indicating that these units may provide a neural substrate for low-frequency SRM.

PMID- 15857967
TI  - Slow and fast inhibition and an H-current interact to create a theta rhythm in a
      model of CA1 interneuron network.
AB  - The oriens-lacunosum moleculare (O-LM) subtype of interneuron is a key component
      in the formation of the theta rhythm (8-12 Hz) in the hippocampus. It is known
      that the CA1 region of the hippocampus can produce theta rhythms in vitro with
      all ionotropic excitation blocked, but the mechanisms by which this rhythmicity
      happens were previously unknown. Here we present a model suggesting that
      individual O-LM cells, by themselves, are capable of producing a single-cell
      theta-frequency firing, but coupled O-LM cells are not capable of producing a
      coherent population theta. By including in the model fast-spiking (FS)
      interneurons, which give rise to IPSPs that decay faster than those of the O-LM
      cells, coherent theta rhythms are produced. The inhibition to O-LM cells from the
      FS cells synchronizes the O-LM cells, but only when the FS cells themselves fire
      at a theta frequency. Reciprocal connections from the O-LM cells to the FS cells
      serve to parse the FS cell firing into theta bursts, which can then synchronize
      the O-LM cells. A component of the model O-LM cell critical to the
      synchronization mechanism is the hyperpolarization-activated h-current. The model
      can robustly reproduce relative phases of theta frequency activity in O-LM and FS
      cells.

PMID- 15857968
TI  - Differential characteristics of face neuron responses within the anterior
      superior temporal sulcus of macaques.
AB  - The anterior superior temporal sulcus (STS) of macaque monkeys is thought to be
      involved in the analysis of incoming perceptual information for face recognition
      or identification; face neurons in the anterior STS show tuning to facial views
      and/or gaze direction in the faces of others. Although it is well known that both
      the anatomical architecture and the connectivity differ between the rostral and
      caudal regions of the anterior STS, the functional heterogeneity of these regions
      is not well understood. We recorded the activity of face neurons in the anterior
      STS of macaque monkeys during the performance of a face identification task, and
      we compared the characteristics of face neuron responses in the caudal and
      rostral regions of the anterior STS. In the caudal region, facial views that
      elicited optimal responses were distributed among all views tested; the majority
      of face neurons responded symmetrically to right and left views. In contrast, the
      face neurons in the rostral region responded optimally to a single oblique view;
      right-left symmetry among the responses of these neurons was less evident.
      Modulation of the face neuron responses according to gaze direction was more
      evident in the rostral region. Some of the face neuron responses were specific to
      a certain combination of a particular facial view and a particular gaze
      direction, whereas others were associated with the relative spatial relationship
      between facial view and gaze direction. Taken together, these results indicated
      the existence of a functional heterogeneity within the anterior STS and suggested
      a plausible hierarchical organization of facial information processing.

PMID- 15857969
TI  - Movement-related correlates of single-cell activity in the medial mammillary
      nucleus of the rat during a pellet-chasing task.
AB  - Although the functional role of the mammillary bodies has remained obscure,
      lesion studies suggest this structure may play a role in memory-in particular,
      memory for spatial information. Indeed, anatomically, the mammillary bodies are
      strongly interconnected with limbic system regions, such as the hipppocampal
      formation, which are also thought to play a role in spatial behavior. Each of
      these limbic regions so far investigated contains cells that signal either the
      momentary location and/or directional heading of an animal as it travels through
      space. In fact, the lateral mammillary nucleus itself contains head direction
      cells, and is thought to be critical for the initial calculation of this
      directional signal. Here, we provide an initial report on cell activity in the
      medial mammillary nucleus. Cells were recorded while rats performed a pellet
      chasing task that has been used for much of the work on place and head direction
      cells. The main findings are 1) approximately 1/3 of the cells showed a
      temporally precise relationship to angular motion of the head, so that they
      differentially indicated clockwise versus counterclockwise angular motion, 2)
      approximately 60% of the cells showed a temporally coarse correlation with
      translational motion, 3) firing rate for almost all cells was strongly modulated
      at theta frequency, and 4) no cells showed evidence of either directional or
      place-related activity. These data suggest that the medial and lateral mammillary
      nuclei together provide the directional and trajectory information thought to be
      critical for generation of the spatial signals in the hippocampal region.

PMID- 15857970
TI  - Spatial sensitivity in the dorsal zone (area DZ) of cat auditory cortex.
AB  - We compared the spatial sensitivity of neural responses in three areas of cat
      auditory cortex: primary auditory cortex (A1), the posterior auditory field
      (PAF), and the dorsal zone (DZ). Stimuli were 80-ms pure tones or broadband noise
      bursts varying in free-field azimuth (in the horizontal plane) or elevation (in
      the vertical median plane), presented at levels 20-40 dB above units' thresholds.
      We recorded extracellular spike activity simultaneously from 16 to 32 sites in
      one or two areas of alpha-chloralose-anesthetized cats. We examined the
      dependence of spike counts and response latencies on stimulus location as well as
      the information transmission by neural spike patterns. Compared with units in A1,
      DZ units exhibited more complex frequency tuning, longer-latency responses,
      increased prevalence and degree of nonmonotonic rate-level functions, and weaker
      responses to noise than to tonal stimulation. DZ responses also showed sharper
      tuning for stimulus azimuth, stronger azimuthal modulation of first-spike
      latency, and enhanced spatial information transmission by spike patterns,
      compared with A1. Each of these findings was similar to differences observed
      between PAF and A1. Compared with PAF, DZ responses were of shorter overall
      latency, and more DZ units preferred stimulation from ipsilateral azimuths, but
      the majority of analyses suggest strong similarity between PAF and DZ responses.
      These results suggest that DZ and A1 are physiologically distinct cortical fields
      and that fields like PAF and DZ might constitute a "belt" region of auditory
      cortex exhibiting enhanced spatial sensitivity and temporal coding of stimulus
      features.

PMID- 15857971
TI  - Visuospatial memory computations during whole-body rotations in roll.
AB  - We used a memory-saccade task to test whether the location of a target, briefly
      presented before a whole-body rotation in roll, is stored in egocentric or in
      allocentric coordinates. To make this distinction, we exploited the fact that
      subjects, when tilted sideways in darkness, make systematic errors when
      indicating the direction of gravity (an allocentric task) even though they have a
      veridical percept of their self-orientation in space. We hypothesized that if
      spatial memory is coded allocentrically, these distortions affect the coding of
      remembered targets and their readout after a body rotation. Alternatively, if
      coding is egocentric, updating for body rotation becomes essential and errors in
      performance should be related to the amount of intervening rotation. Subjects (n
      = 6) were tested making saccades to remembered world-fixed targets after passive
      body tilts. Initial and final tilt angle ranged between -120 degrees CCW and 120
      degrees CW. The results showed that subjects made large systematic directional
      errors in their saccades (up to 90 degrees ). These errors did not occur in the
      absence of intervening body rotation, ruling out a memory degradation effect.
      Regression analysis showed that the errors were closely related to the amount of
      subjective allocentric distortion at both the initial and final tilt angle,
      rather than to the amount of intervening rotation. We conclude that the brain
      uses an allocentric reference frame, possibly gravity-based, to code visuospatial
      memories during whole-body tilts. This supports the notion that the brain can
      define information in multiple frames of reference, depending on sensory inputs
      and task demands.

PMID- 15857972
TI  - Selective progesterone receptor modulator development and use in the treatment of
      leiomyomata and endometriosis.
AB  - Selective progesterone receptor modulators (SPRMs) represent a new class of
      progesterone receptor ligands. SPRMs exert clinically relevant tissue-selective
      progesterone agonist, antagonist, or mixed agonist/antagonist effects on various
      progesterone target tissues in vivo. Asoprisnil (J867) is the first SPRM to reach
      an advanced stage of clinical development for the treatment of symptomatic
      uterine fibroids and endometriosis. Asoprisnil belongs to the class of 11beta
      benzaldoxime-substituted estratrienes that exhibit partial progesterone
      agonist/antagonist effects with high progesterone receptor specificity in animals
      and humans. Asoprisnil has no antiglucocorticoid activity in humans at
      therapeutic doses. It exhibits endometrial antiproliferative effects on the
      endometrium and breast in primates. Unlike progesterone antagonists, asoprisnil
      does not induce labor in relevant models of pregnancy and parturition. It induces
      amenorrhea primarily by targeting the endometrium. In human subjects with uterine
      fibroids, asoprisnil suppressed both the duration and intensity of uterine
      bleeding in a dose-dependent manner and reduced tumor volume in the absence of
      estrogen deprivation. In subjects with endometriosis, asoprisnil was effective in
      reducing nonmenstrual pain and dysmenorrhea. Asoprisnil may, therefore, provide a
      novel, tissue-selective approach to control endometriosis-related pain. SPRMs
      have the potential to become a novel treatment of uterine fibroids and
      endometriosis.

PMID- 15857973
TI  - Reflections on the discovery and significance of estrogen receptor beta.
AB  - We have known for many years that estrogen is more than the female hormone. It is
      essential in the male gonads, and in both sexes, estrogen has functions in the
      skeleton and central nervous system, on behavior, and in the cardiovascular and
      immune systems. An important aspect of the discovery of estrogen receptor (ER)
      beta is that the diverse functions of estrogen can now be divided into those
      mediated by ERalpha and those mediated by ERbeta. Pharmacological exploitation of
      this division of the labors of estrogen is facilitated by the ligand-binding
      specificity and selective tissue distribution of the two ERs. Because the ligand
      binding domains of ERalpha and ERbeta are significantly different from each
      other, selective ligands can be (and have been) developed to target the
      estrogenic pathway that is malfunctioning, without interfering with the other
      estrogen-regulated pathways. Because of the absence of ERbeta from the adult
      pituitary and endometrium, ERbeta agonists can be used to target ERbeta with no
      risk of adverse effects from chemical castration and uterine cancer. Some of the
      diseases in which there is hope that ERbeta agonists will be of benefit are
      prostate cancer, autoimmune diseases, colon cancer, malignancies of the immune
      system, and neurodegeneration.

PMID- 15857974
TI  - High-level expression of Marek's disease virus glycoprotein C is detrimental to
      virus growth in vitro.
AB  - Expression levels of Marek's disease virus (MDV) glycoprotein C (gC) are
      significantly reduced after serial virus passage in cell culture. Reduced gC
      expression coincides with enhanced MDV growth in vitro and attenuation. To
      analyze this phenomenon in detail, a full-length infectious MDV clone was
      modified by Red-based and shuttle mutagenesis in Escherichia coli. Besides a gC
      negative deletion mutant harboring a kanamycin resistance gene, a markerless
      mutant with the U(L)44 gene deleted was constructed. On the basis of this
      deletion mutant, the original or a modified U(L)44 gene with a mutated start
      codon (AUG-->ACG) was reinserted into the authentic locus. Similarly, mutants
      expressing authentic gC or the start codon mutation under the control of a strong
      constitutive promoter were generated. In vitro studies demonstrated that gC
      deletion mutants induced twofold-larger plaques than the parental virus did,
      whereas constitutive overexpression of the glycoprotein resulted in a more than
      twofold reduction in plaque size. In addition, plaque sizes of the gC deletion
      mutant were reduced when virus was grown using supernatants from cells infected
      with parental virus, but supernatants obtained from cells infected with the gC
      deletion mutant had no measurable effect on plaque size. The results indicated
      that (i) expression of MDV gC, albeit at low levels in a highly passaged virus,
      had a significant negative impact on the cell-to-cell spread capabilities of the
      virus, which was alleviated in its absence and exacerbated by its overexpression,
      and that (ii) this activity was mediated by the secreted form of MDV gC.

PMID- 15857975
TI  - Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute
      respiratory syndrome by an animal study, epitope mapping, and analysis of spike
      variants.
AB  - In this report, the antiviral activity of 80R immunoglobulin G1 (IgG1), a human
      monoclonal antibody against severe acute respiratory syndrome coronavirus (SARS
      CoV) spike (S) protein that acts as a viral entry inhibitor in vitro, was
      investigated in vivo in a mouse model. When 80R IgG1 was given prophylactically
      to mice at doses therapeutically achievable in humans, viral replication was
      reduced by more than 4 orders of magnitude to below assay limits. The essential
      core region of S protein required for 80R binding was identified as a
      conformationally sensitive fragment (residues 324 to 503) that overlaps the
      receptor ACE2-binding domain. Amino acids critical for 80R binding were
      identified. In addition, the effects of various 80R-binding domain amino acid
      substitutions which occur in SARS-like-CoV from civet cats, and which evolved
      during the 2002/2003 outbreak and in a 2003/2004 Guangdong index patient, were
      analyzed. The results demonstrated that the vast majority of SARS-CoVs are
      sensitive to 80R. We propose that by establishing the susceptibility and
      resistance profiles of newly emerging SARS-CoVs through early S1 genotyping of
      the core 180-amino-acid neutralizing epitope of 80R, an effective
      immunoprophylaxis strategy with 80R should be possible in an outbreak setting.
      Our study also cautions that for any prophylaxis strategy based on neutralizing
      antibody responses, whether by passive or active immunization, a genotyping
      monitor will be necessary for effective use.

PMID- 15857976
TI  - Phenotypic hypersusceptibility to multiple protease inhibitors and low
      replicative capacity in patients who are chronically infected with human
      immunodeficiency virus type 1.
AB  - Increased susceptibility to the protease inhibitors saquinavir and amprenavir has
      been observed in human immunodeficiency virus type 1 (HIV-1) with specific
      mutations in protease (V82T and N88S). Increased susceptibility to ritonavir has
      also been described in some viruses from antiretroviral agent-naive patients with
      primary HIV-1 infection in association with combinations of amino acid changes at
      polymorphic sites in the protease. Many of the viruses displaying increased
      susceptibility to protease inhibitors also had low replication capacity. In this
      retrospective study, we analyze the drug susceptibility phenotype and the
      replication capacity of virus isolates obtained at the peaks of viremia during
      five consecutive structured treatment interruptions in 12 chronically HIV-1
      infected patients. Ten out of 12 patients had at least one sample with protease
      inhibitor hypersusceptibility (change </=0.4-fold) to one or more protease
      inhibitor. Hypersusceptibility to different protease inhibitors was observed at
      variable frequency, ranging from 38% to amprenavir to 11% to nelfinavir. Pairwise
      comparisons between susceptibilities for the protease inhibitors showed a
      consistent correlation among all pairs. There was also a significant relationship
      between susceptibility to protease inhibitors and replication capacity in all
      patients. Replication capacity remained stable over the course of repetitive
      cycles of structured treatment interruptions. We could find no association
      between in vitro replication capacity and in vivo plasma viral load doubling time
      and CD4(+) and CD8(+) T-cell counts at each treatment interruption. Several
      mutations were associated with hypersusceptibility to each protease inhibitor in
      a univariate analysis. This study extends the association between
      hypersusceptibility to protease inhibitors and low replication capacity to virus
      isolated from chronically infected patients and highlights the complexity of
      determining the genetic basis of this phenomenon. The potential clinical
      relevance of protease inhibitor hypersusceptibility and low replication capacity
      to virologic response to protease inhibitor-based therapies deserves to be
      investigated further.

PMID- 15857977
TI  - Variant upstream regulatory region sequences differentially regulate human
      papillomavirus type 16 DNA replication throughout the viral life cycle.
AB  - While the central role of the viral upstream regulatory region (URR) in the human
      papillomavirus (HPV) life cycle has been well established, its effects on viral
      replication factor expression and plasmid replication of HPV type 16 (HPV16)
      remain unclear. Some nonprototypic variants of HPV16 contain altered URR
      sequences and are considered to increase the oncogenic risk of infections. To
      determine the relationship between viral replication and variant URRs, hybrid
      viral genomes were constructed with the replication-competent HPV16 prototype W12
      and analyzed in assays which recapitulate the different phases of normal viral
      replication. The establishment efficiencies of hybrid HPV16 genomes differed
      about 20-fold among European prototypes and variants from Africa and America.
      Generally, European and African genomes exhibited the lowest replication
      efficiencies. The high replication levels observed with American variants were
      primarily attributable to their efficient expression of the replication factors
      E1 and E2. The maintenance levels of these viral genomes varied about fivefold,
      which correlated with their respective establishment phenotypes and published
      P(97) activities. Vegetative DNA amplification could also be observed with
      replicating HPV16 genomes. These results indicate that efficient E1/E2 expression
      and elevated plasmid replication levels during the persistent stage of infection
      may comprise a risk factor in HPV16-mediated oncogenesis.

PMID- 15857978
TI  - Exploiting cis-acting replication elements to direct hepatitis C virus-dependent
      transgene expression.
AB  - We describe here a novel targeting gene therapy strategy to direct gene
      expression responsive to hepatitis C virus (HCV). The goal was approached by
      engineering a construct containing the antisense sequence of the transgene and
      internal ribosome entry site of encephalomyocarditis virus flanked by 5'- and 3'
      end sequences of HCV cDNA that contain cis-acting replication elements. Thus,
      expression of the transgene is only promoted when the minus-strand RNA has been
      synthesized by the functional replication machinery present in infected cells.
      Reporter assay and strand-specific reverse transcription-PCR showed selective
      transgene expression in Huh-7 cells harboring an autonomously replicating HCV
      subgenome but remaining silent in uninfected cells. Furthermore, using the
      cytosine deaminase suicide gene as a transgene coupled with recombinant
      adenovirus delivery, we demonstrated that cytosine deaminase was specifically
      expressed in replicon cells, resulting in marked chemosensitization of replicon
      cells to the cytotoxic effects of flucytosine. This new targeting strategy could
      be extended to other single-stranded RNA viruses encoding the unique RNA
      dependent RNA polymerase that has no parallel in mammalian cells.

PMID- 15857979
TI  - Identification of cis-acting elements that mediate the replication and
      maintenance of human papillomavirus type 16 genomes in Saccharomyces cerevisiae.
AB  - Papillomaviruses contain small double-stranded DNA genomes that are maintained in
      persistently infected mammalian host epithelia as nuclear plasmids and rely upon
      the host replication machinery for replication. Papillomaviruses encode a DNA
      helicase, E1, which can specifically bind to the viral genome and support DNA
      synthesis. Under some conditions in mammalian cells, E1 is not required for viral
      DNA synthesis, leading to the hypothesis that papillomavirus DNA can be
      replicated solely by the host replication machinery. This machinery is highly
      conserved among eukaryotes. We and others found that papillomavirus DNA could
      replicate in a simple eukaryote, Saccharomyces cerevisiae. Specifically,
      papillomavirus DNA could substitute for the function of the autonomously
      replicating sequence (ARS) and centromere (CEN) elements that are normally both
      required for the stable replication of extrachromosomal DNAs in yeast.
      Furthermore, this form of replication in yeast was E1 independent. In this study,
      we map the elements in the human papillomavirus type 16 (HPV16) genome that can
      substitute for yeast ARS and CEN elements. A single element, termed rep, was
      identified that can substitute for ARS, and multiple elements, termed mtc, could
      substitute for CEN. The location of one of these mtc elements overlaps the
      location of rep, and this approximately 1,000-bp region of HPV16 was sufficient
      to support stable replication of a bacterial-yeast shuttle plasmid deleted of
      both ARS and CEN elements.

PMID- 15857980
TI  - Roles of CD4+ T-cell-independent and -dependent antibody responses in the control
      of influenza virus infection: evidence for noncognate CD4+ T-cell activities that
      enhance the therapeutic activity of antiviral antibodies.
AB  - Previous studies have indicated that B cells make a significant contribution to
      the resolution of influenza virus infection. To determine how B cells participate
      in the control of the infection, we transferred intact, major histocompatibility
      complex class II (MHC-II)-negative or B-cell receptor (BCR)-transgenic spleen
      cells into B-cell-deficient and CD8(+) T-cell-depleted muMT mice, termed muMT(
      8), and tested them for ability to recover from infection. muMT(-8) mice that
      received no spleen cells invariably succumbed to the infection within 20 days,
      indicating that CD4(+) T-cell activities had no significant therapeutic activity
      on their own; in fact, they were harmful and decreased survival time.
      Interestingly, however, they became beneficial in the presence of antiviral
      antibody (Ab). Injection of MHC-II((-/-)) spleen cells, which can provide CD4(+)
      T-cell-independent (TI) but not T-cell-dependent (TD) activities, delayed
      mortality but only rarely resulted in clearance of the infection. By contrast,
      80% of muMT(-8) mice injected with normal spleen cells survived and resolved the
      infection. Transfer of BCR-transgenic spleen cells, which contained approximately
      10 times fewer virus-specific precursor B cells than normal spleen cells, had no
      significant impact on the course of the infection. Taken together, the results
      suggest that B cells contribute to the control of the infection mainly through
      production of virus-specific Abs and that the TD Ab response is therapeutically
      more effective than the TI response. In addition, CD4(+) T cells appear to
      contribute, apart from promoting the TD Ab response, by improving the therapeutic
      activity of Ab-mediated effector mechanisms.

PMID- 15857981
TI  - Mitogen-activated protein kinases regulate LSF occupancy at the human
      immunodeficiency virus type 1 promoter.
AB  - Human immunodeficiency virus type 1 (HIV-1) establishes a persistent,
      nonproductive state within a small population of memory CD4(+) cells. The
      transcription factor LSF binds to sequences within the HIV-1 long terminal repeat
      (LTR) initiation region and recruits a second factor, YY1, to the LTR. These
      factors then cooperatively recruit histone deacetylase 1 to the LTR, resulting in
      inhibition of transcription. This appears to be one mechanism contributing to HIV
      persistence within resting CD4(+) T cells. We sought to further detail LSF
      binding to the HIV-1 LTR and factors that regulate LSF occupancy. We find that
      LSF binds the LTR as a tetramer and that binding is regulated by phosphorylation
      mediated by mitogen-activated protein kinases (MAPKs). In vitro, phosphorylation
      of LSF by Erk decreases binding to the LTR, while binding is increased by p38
      phosphorylation. LSF occupancy at LTR chromatin is increased by the p38 agonist
      anisomycin and decreased by specific p38 inhibition. p38 inhibition also results
      in increased acetylation of histone H4 at the LTR nucleosome adjacent to the LSF
      binding site. p38 inhibition also blocked the ability of YY1 to inhibit
      activation of the integrated HIV promoter. Finally, HIV was recovered from the
      resting CD4(+) T cells of aviremic, HIV-infected donors upon treatment of these
      cells with specific inhibitor of p38. These data suggest that the MAPK pathway
      regulates LSF binding to the LTR and thereby one aspect of the regulation of HIV
      expression. This mechanism could be exploited as a novel therapeutic target to
      disrupt latent HIV infection.

PMID- 15857982
TI  - Human rhinovirus type 89 variants use heparan sulfate proteoglycan for cell
      attachment.
AB  - We have previously isolated mutants of the major-group human rhinovirus type 89
      that grow in cells deficient in intercellular adhesion molecule 1 (ICAM-1), the
      receptor used by the wild-type virus for cell entry [A. Reischl, M. Reithmayer,
      G. Winsauer, R. Moser, I. Goesler, and D. Blaas., J. Virol. 75:9312-9319, 2001].
      We now demonstrate that one of these variants utilizes heparan sulfate
      proteoglycan (HSPG) as a cellular receptor. Adaptation to ICAM-1-deficient cells
      not only resulted in the newly acquired receptor specificity but also rendered
      the virus less stable at low pH and at elevated temperatures. This instability
      might compensate for the absence of the uncoating activity of ICAM-1. Whereas
      wild-type virus infection via ICAM-1 proceeded in the presence of the vesicular
      H(+)-ATPase inhibitor bafilomycin A1, infection by the mutant via HSPG was
      prevented by the drug. This suggests that the low pH prevailing in endosomal
      compartments is required for uncoating in the absence of the catalytic activity
      of ICAM-1.

PMID- 15857983
TI  - The immune response to human metapneumovirus is associated with aberrant immunity
      and impaired virus clearance in BALB/c mice.
AB  - Human metapneumovirus (HMPV), recently identified in isolates from children
      hospitalized with acute respiratory tract illness, is associated with clinical
      diagnosis of pneumonia, asthma exacerbation, and acute bronchiolitis in young
      children. HMPV has been shown to cocirculate with respiratory syncytial virus
      (RSV) and mediate clinical disease features similarly to RSV. Little is known
      regarding the pathophysiology or immune response associated with HMPV infection;
      thus, animal models are needed to better understand the mechanisms of immunity
      and disease pathogenesis associated with infection. In this study, we examine
      features of the innate and adaptive immune response to HMPV infection in a BALB/c
      mouse model. Primary HMPV infection elicits weak innate and aberrant adaptive
      immune responses characterized by induction of a Th2-type cytokine response at
      later stages of infection that coincides with increased interleukin-10 expression
      and persistent virus replication in the lung. Examination of the cytotoxic T
      lymphocyte and antibody response to HMPV infection revealed a delayed response,
      but passive transfer of HMPV-specific antibodies provided considerable
      protection. These features are consistent with virus persistence and indicate
      that the immune response to HMPV is unique compared to the immune response to
      RSV.

PMID- 15857984
TI  - Characterization of the interaction of lassa fever virus with its cellular
      receptor alpha-dystroglycan.
AB  - The cellular receptor for the Old World arenaviruses Lassa fever virus (LFV) and
      lymphocytic choriomeningitis virus (LCMV) has recently been identified as alpha
      dystroglycan (alpha-DG), a cell surface receptor that provides a molecular link
      between the extracellular matrix and the actin-based cytoskeleton. In the present
      study, we show that LFV binds to alpha-DG with high affinity in the low-nanomolar
      range. Recombinant vesicular stomatitis virus pseudotyped with LFV glycoprotein
      (GP) adopted the receptor binding characteristics of LFV and depended on alpha-DG
      for infection of cells. Mapping of the binding site of LFV on alpha-DG revealed
      that LFV binding required the same domains of alpha-DG that are involved in the
      binding of LCMV. Further, LFV was found to efficiently compete with laminin
      alpha1 and alpha2 chains for alpha-DG binding. Together with our previous studies
      on receptor binding of the prototypic immunosuppressive LCMV isolate LCMV clone
      13, these findings indicate a high degree of conservation in the receptor binding
      characteristics between the highly human-pathogenic LFV and murine
      immunosuppressive LCMV isolates.

PMID- 15857985
TI  - Virus-specific CD4+ and CD8+ cytotoxic T-cell responses and long-term T-cell
      memory in individuals vaccinated against polio.
AB  - The presence of poliovirus (PV)-specific CD4(+) T cells in individuals vaccinated
      against polio has been shown, but CD8(+) T-cell responses have not been
      described. Here, we functionally characterize the CD4(+) T-cell response and show
      for the first time that dendritic cells and macrophages can stimulate PV-specific
      CD8(+) T-cell responses in vitro from vaccinees. Both CD4(+) T and CD8(+) T cells
      secrete gamma interferon in response to PV antigens and are cytotoxic via the
      perforin/granzyme B-mediated pathway. Furthermore, the T cells also recognize and
      kill Sabin 1 vaccine-infected targets. The macrophage-stimulated CD4(+) T and
      CD8(+) T cells most likely represent memory T cells that persist for long periods
      in vaccinated individuals. Thus, immunity to PV vaccination involves not only an
      effective neutralizing antibody titer but also long-term CD4(+) and CD8(+)
      cytotoxic T-cell responses.

PMID- 15857986
TI  - Amino acid 36 in the human immunodeficiency virus type 1 gp41 ectodomain controls
      fusogenic activity: implications for the molecular mechanism of viral escape from
      a fusion inhibitor.
AB  - We have previously described a human immunodeficiency virus type 1 (HIV-1)
      proviral clone, pL2, derived from defective viral particles with higher
      fusogenicity than the prototypic NL4-3 virus. In this study, we attempted to
      determine the region that confers the enhanced fusion activity by creating
      envelope recombinants between pL2 and pNL4-3, as well as point mutants based on
      pNL4-3. The results indicate that amino acid 36 of gp41 is key for the fusogenic
      activity and infectivity enhancement and that glycine 36 (36G) of gp41 in pL2 is
      conserved in nearly all HIV-1 isolates except for pNL4-3. The mutation 36G-->D in
      a primary-isolate-derived Env decreased syncytium-forming activity and
      infectivity. The assays for cell-cell fusion and viral binding suggested that the
      enhanced fusion mediated by the 36D-->G mutation is not due to increased binding
      efficiency but is directly due to actual enhancement of viral fusion activity.
      Interestingly, this amino acid position is exactly equivalent to that at which
      the mutation of HIV-1 isolates that have escaped from a fusion inhibitor,
      enfuvirtide (T-20), has been frequently observed. The correlation between these
      previous findings and our findings was suggested by structural analysis. Our
      finding, therefore, has implications for a molecular basis of the viral escape
      from this drug.

PMID- 15857987
TI  - Targeting human glioblastoma cells: comparison of nine viruses with oncolytic
      potential.
AB  - Brain tumors classified as glioblastomas have proven refractory to treatment and
      generally result in death within a year of diagnosis. We used seven in vitro
      tests and one in vivo trial to compare the efficacy of nine different viruses for
      targeting human glioblastoma. Green fluorescent protein (GFP)-expressing
      vesicular stomatitis (VSV), Sindbis virus, pseudorabies virus (PRV), adeno
      associated virus (AAV), and minute virus of mice i-strain (MVMi) and MVMp all
      infected glioblastoma cells. Mouse and human cytomegalovirus, and simian virus 40
      showed only low levels of infection or GFP expression. VSV and Sindbis virus
      showed strong cytolytic actions and high rates of replication and spread, leading
      to an elimination of glioblastoma. PRV and both MVM strains generated more modest
      lytic effects and replication capacity. VSV showed a similar oncolytic profile on
      U-87 MG and M059J glioblastoma. In contrast, Sindbis virus showed strong
      preference for U-87 MG, whereas MVMi and MVMp preferred M059J. Sindbis virus and
      both MVM strains showed highly tumor-selective actions in glioblastoma plus
      fibroblast coculture. VSV and Sindbis virus were serially passaged on
      glioblastoma cells; we isolated a variant, VSV-rp30, that had increased
      selectivity and lytic capacity in glioblastoma cells. VSV and Sindbis virus were
      very effective at replicating, spreading within, and selectively killing human
      glioblastoma in an in vivo mouse model, whereas PRV and AAV remained at the
      injection site with minimal spread. Together, these data suggest that four (VSV,
      Sindbis virus, MVMi, and MVMp) of the nine viruses studied merit further analysis
      for potential therapeutic actions on glioblastoma.

PMID- 15857988
TI  - Human serum facilitates hepatitis C virus infection, and neutralizing responses
      inversely correlate with viral replication kinetics at the acute phase of
      hepatitis C virus infection.
AB  - The factors leading to spontaneous clearance of hepatitis C virus (HCV) or to
      viral persistence are elusive. Understanding virus-host interactions that enable
      acute HCV clearance is key to the development of more effective therapeutic and
      prophylactic strategies. Here, using a sensitive neutralization assay based on
      infectious HCV pseudoparticles (HCVpp), we have studied the kinetics of humoral
      responses in a cohort of acute-phase patients infected during a single nosocomial
      outbreak in a hemodialysis center. The 17 patients were monitored for the
      spontaneous outcome of HCV infection for 6 months before a treatment decision was
      made. Blood samples were taken frequently (15 +/- 4 per patient). Phylogenetic
      analysis of the predominant virus(es) revealed infection by only one of two
      genotype 1b strains. While all patients seroconverted, their sera induced two
      opposing effects in HCVpp infection assays: inhibition and facilitation.
      Furthermore, the ability of sera to facilitate or inhibit infection correlated
      with the presence of either infecting HCV strain and divided the patients into
      two groups. In group 1, the progressive emergence of a relatively strong
      neutralizing response correlated with a fluctuating decrease in high initial
      viremia, leading to control of viral replication. Patients in group 2 failed to
      reduce viremia within the acute phase, and no neutralizing responses were
      detected despite seroconversion. Strikingly, sera of group 2, as well as naive
      sera, facilitated infection by HCVpp displaying HCV glycoproteins from different
      genotypes and strains, including those retrieved from patients. These results
      provide new insights into the mechanisms of viral persistence and immune control
      of viremia.

PMID- 15857989
TI  - Chinchilla and murine models of upper respiratory tract infections with
      respiratory syncytial virus.
AB  - Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract
      infections in infants and the elderly. While the primary infection is the most
      serious, reinfection of the upper airway throughout life is the rule. Although
      relatively little is known about either RSV infection of the upper respiratory
      tract or host mucosal immunity to RSV, recent literature suggests that RSV is the
      predominant viral pathogen predisposing to bacterial otitis media (OM). Herein,
      we describe mouse and chinchilla models of RSV infection of the nasopharynx and
      Eustachian tube. Both rodent hosts were susceptible to RSV infection of the upper
      airway following intranasal challenge; however, the chinchilla proved to be more
      permissive than the mouse. The chinchilla model will likely be extremely useful
      to test the role of RSV in bacterial OM and the efficacy of RSV vaccine
      candidates designed to provide mucosal and cytotoxic T-lymphocyte immunity.
      Ultimately, we hope to investigate the relative ability of these candidates to
      potentially protect against viral predisposal to bacterial OM.

PMID- 15857990
TI  - Constitutive activation of the transcription factor NF-kappaB results in impaired
      borna disease virus replication.
AB  - The inducible transcription factor NF-kappaB is commonly activated upon RNA virus
      infection and is a key player in the induction and regulation of the innate
      immune response. Borna disease virus (BDV) is a neurotropic negative-strand RNA
      virus, which replicates in the nucleus of the infected cell and causes a
      persistent infection that can lead to severe neurological disorders. To
      investigate the activation and function of NF-kappaB in BDV-infected cells, we
      stably transfected the highly susceptible neuronal guinea pig cell line CRL with
      a constitutively active (IKK EE) or dominant-negative (IKK KD) regulator of the
      IKK/NF-kappaB signaling pathway. While BDV titers were not affected in cells with
      impaired NF-kappaB signaling, the expression of an activated mutant of IkappaB
      kinase (IKK) resulted in a strong reduction in the intracellular viral titer in
      CRL cells. Electrophoretic mobility shift assays and luciferase reporter gene
      assays revealed that neither NF-kappaB nor interferon regulatory factors (IRFs)
      were activated upon acute BDV infection of wild-type or vector-transfected CRL
      cells. However, when IKK EE-transfected cells were used as target cells for BDV
      infection, DNA binding to an IRF3/7-responsive DNA element was detectable. Since
      IRF3/7 is a key player in the antiviral interferon response, our data indicate
      that enhanced NF-kappaB activity in the presence of BDV leads to the induction of
      antiviral pathways resulting in reduced virus titers. Consistent with this
      observation, the anti-BDV activity of NF-kappaB preferentially spread to areas of
      the brains of infected rats where activated NF-kappaB was not detectable.

PMID- 15857991
TI  - Myxoma virus M141R expresses a viral CD200 (vOX-2) that is responsible for down
      regulation of macrophage and T-cell activation in vivo.
AB  - M141R is a myxoma virus gene that encodes a cell surface protein with significant
      amino acid similarity to the family of cellular CD200 (OX-2) proteins implicated
      in the regulation of myeloid lineage cell activation. The creation of an M141R
      deletion mutant myxoma virus strain (vMyx141KO) and its subsequent infection of
      European rabbits demonstrated that M141R is required for the full development of
      a lethal infection in vivo but is not required for efficient virus replication in
      susceptible cell lines in vitro. Minor secondary sites of infection were detected
      in the majority of rabbits infected with the M141R deletion mutant, demonstrating
      that the M141R protein is not required for the dissemination of virus within the
      host. When compared to wild-type myxoma virus-infected rabbits, vMyx141KO
      infected rabbits showed higher activation levels of both monocytes/macrophages
      and lymphocytes in situ through assessments of inducible nitric oxide synthase
      positive and CD25(+) infiltrating cells in infected and lymphoid tissues.
      Purified peripheral blood mononuclear cells from vMyx141KO-infected rabbits
      demonstrated an increased ability to express gamma interferon upon activation by
      phorbol myristate acetate plus ionomycin compared to cells purified from wild
      type myxoma virus-infected rabbits. We concluded that the M141R protein is a bona
      fide CD200-like immunomodulator protein which is required for the full
      pathogenesis of myxoma virus in the European rabbit and that its loss from the
      virus results in increased activation levels of macrophages in infected lesions
      and draining lymph nodes as well as an increased activation level of circulating
      T lymphocytes during infection. We propose a model whereby M141R transmits
      inhibitory signals to tissue macrophages, and possibly resident CD200R(+)
      dendritic cells, that reduce their ability to antigenically prime lymphocytes and
      possibly provides anergic signals to T cells directly.

PMID- 15857992
TI  - Functional mimicry of a human immunodeficiency virus type 1 coreceptor by a
      neutralizing monoclonal antibody.
AB  - Interaction of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope
      glycoprotein with the primary receptor, CD4, promotes binding to a chemokine
      receptor, either CCR5 or CXCR4. The chemokine receptor-binding site on gp120
      elicits CD4-induced (CD4i) antibodies in some HIV-1-infected individuals. Like
      CCR5 itself, the CD4i antibody 412d exhibits a preference for CCR5-using HIV-1
      strains and utilizes sulfated tyrosines to achieve binding to gp120. Here, we
      show that 412d binding requires the gp120 beta19 strand and the base of the V3
      loop, elements that are important for the binding of the CCR5 N terminus. Two
      gp120 residues in the V3 loop base determined 412d preference for CCR5-using HIV
      1 strains. A chimeric molecule in which the 412d heavy-chain third
      complementarity-determining loop sequence replaces the CCR5 N terminus functioned
      as an efficient second receptor, selectively supporting the entry of CCR5-using
      HIV-1 strains. Sulfation of N-terminal tyrosines contributed to the function of
      this chimeric receptor. These results emphasize the close mimicry of the CCR5 N
      terminus by the gp120-interactive region of a naturally elicited CD4i antibody.

PMID- 15857993
TI  - Nuclear localization of the Nipah virus W protein allows for inhibition of both
      virus- and toll-like receptor 3-triggered signaling pathways.
AB  - The Nipah virus V and W proteins, which are encoded by the P gene via RNA
      editing, have a common N-terminal domain but unique C-terminal domains. They
      localize to the cytoplasm and nucleus, respectively, and have both been shown to
      function as inhibitors of JAK/STAT signaling. Here we report that V and W
      proteins also block virus activation of the beta interferon (IFN-beta) promoter
      and the IFN regulatory factor 3 (IRF3)-responsive IFN-stimulated gene 54
      promoter. Surprisingly, only W protein shows strong inhibition of promoter
      activation in response to stimulation of Toll-like receptor 3 (TLR3) by
      extracellular double-stranded RNA. This activity is dependent on the nuclear
      localization of W protein. Within the unique C-terminal domain of W protein, we
      have identified a nuclear localization signal (NLS) that requires basic residues
      at positions 439, 440, and 442. This NLS is responsible for mediating the
      preferential interaction of W protein with karyopherin-alpha 3 and karyopherin
      alpha 4. Nuclear localization of W protein therefore enables it to target both
      virus and TLR3 pathways, whereas the cytoplasmic V protein is restricted to
      inhibiting the virus pathway. We propose that this discrepancy is in part due to
      the V protein being less able to block signaling in response to the kinase, TBK
      1, whereas both V and W can prevent promoter activation in response to
      IKKepsilon. We demonstrate that, when the TLR3 pathway is stimulated, the levels
      of phosphorylated IRF3 are reduced in the presence of W protein but not V
      protein, confirming the differential effects of these proteins and illustrating
      that W protein-mediated inhibition is due to a loss of active IRF3.

PMID- 15857994
TI  - Biologic and genetic characterization of a panel of 60 human immunodeficiency
      virus type 1 isolates, representing clades A, B, C, D, CRF01_AE, and CRF02_AG,
      for the development and assessment of candidate vaccines.
AB  - A critical priority for human immunodeficiency virus type 1 (HIV-1) vaccine
      development is standardization of reagents and assays for evaluation of immune
      responses elicited by candidate vaccines. To provide a panel of viral reagents
      from multiple vaccine trial sites, 60 international HIV-1 isolates were expanded
      in peripheral blood mononuclear cells and characterized both genetically and
      biologically. Ten isolates each from clades A, B, C, and D and 10 isolates each
      from CRF01_AE and CRF02_AG were prepared from individuals whose HIV-1 infection
      was evaluated by complete genome sequencing. The main criterion for selection was
      that the candidate isolate was pure clade or pure circulating recombinant. After
      expansion in culture, the complete envelope (gp160) of each isolate was verified
      by sequencing. The 50% tissue culture infectious dose and p24 antigen
      concentration for each viral stock were determined; no correlation between these
      two biologic parameters was found. Syncytium formation in MT-2 cells and CCR5 or
      CXCR4 coreceptor usage were determined for all isolates. Isolates were also
      screened for neutralization by soluble CD4, a cocktail of monoclonal antibodies,
      and a pool of HIV-1-positive patient sera. The panel consists of 49 nonsyncytium
      inducing isolates that use CCR5 as a major coreceptor and 11 syncytium-inducing
      isolates that use only CXCR4 or both coreceptors. Neutralization profiles suggest
      that the panel contains both neutralization-sensitive and -resistant isolates.
      This collection of HIV-1 isolates represents the six major globally prevalent
      strains, is exceptionally large and well characterized, and provides an important
      resource for standardization of immunogenicity assessment in HIV-1 vaccine
      trials.

PMID- 15857995
TI  - Receptor-independent spread of a highly neurotropic murine coronavirus JHMV
      strain from initially infected microglial cells in mixed neural cultures.
AB  - Although neurovirulent mouse hepatitis virus (MHV) strain JHMV multiplies in a
      variety of brain cells, expression of its receptor carcinoembryonic antigen cell
      adhesion molecule 1 (CEACAM 1) (MHVR) is restricted only in microglia. The
      present study was undertaken to clarify the mechanism of an extensive JHMV
      infection in the brain by using neural cells isolated from mouse brain. In
      contrast to wild-type (wt) JHMV, a soluble-receptor-resistant mutant (srr7)
      infects and spreads solely in an MHVR-dependent fashion (F. Taguchi and S.
      Matsuyama, J. Virol. 76:950-958, 2002). In mixed neural cell cultures, srr7
      infected a limited number of cells and infection did not spread, although wt JHMV
      induced syncytia in most of the cells. srr7-infected cells were positive for GS
      lectin, a microglia marker. Fluorescence-activated cell sorter analysis showed
      that about 80% of the brain cells stained with anti-MHVR antibody (CC1) were also
      positive for GS-lectin. Pretreatment of those cells with CC1 prevented virus
      attachment to the cell surface and also blocked virus infection. These results
      show that microglia express functional MHVR that mediates JHMV infection. As
      expected, in microglial cell-enriched cultures, both srr7and wt JHMV produced
      syncytia in a majority of cells. Treatment with CC1 of mixed neural cell cultures
      and microglia cultures previously infected with wt virus failed to block the
      spread of infection, indicating that wt infection spreads in an MHVR-independent
      fashion. Thus, the present study indicates that microglial cells are the major
      population of the initial target for MHV infection and that the wt spreads from
      initially infected microglia to a variety of cells in an MHVR-independent
      fashion.

PMID- 15857996
TI  - The B30.2(SPRY) domain of the retroviral restriction factor TRIM5alpha exhibits
      lineage-specific length and sequence variation in primates.
AB  - Tripartite motif (TRIM) proteins are composed of RING, B-box 2, and coiled coil
      domains. Some TRIM proteins, such as TRIM5alpha, also possess a carboxy-terminal
      B30.2(SPRY) domain and localize to cytoplasmic bodies. TRIM5alpha has recently
      been shown to mediate innate intracellular resistance to retroviruses, an
      activity dependent on the integrity of the B30.2 domain, in particular primate
      species. An examination of the sequences of several TRIM proteins related to
      TRIM5 revealed the existence of four variable regions (v1, v2, v3, and v4) in the
      B30.2 domain. Species-specific variation in TRIM5alpha was analyzed by
      amplifying, cloning, and sequencing nonhuman primate TRIM5 orthologs. Lineage
      specific expansion and sequential duplication occurred in the TRIM5alpha B30.2 v1
      region in Old World primates and in v3 in New World monkeys. We observed
      substitution patterns indicative of selection bordering these particular B30.2
      domain variable elements. These results suggest that occasional, complex changes
      were incorporated into the TRIM5alpha B30.2 domain at discrete time points during
      the evolution of primates. Some of these time points correspond to periods during
      which primates were exposed to retroviral infections, based on the appearance of
      particular endogenous retroviruses in primate genomes. The results are consistent
      with a role for TRIM5alpha in innate immunity against retroviruses.

PMID- 15857997
TI  - Discovery of small-molecule human immunodeficiency virus type 1 entry inhibitors
      that target the gp120-binding domain of CD4.
AB  - The interaction between human immunodeficiency virus type 1 (HIV-1) gp120 and the
      CD4 receptor is highly specific and involves relatively small contact surfaces on
      both proteins according to crystal structure analysis. This molecularly conserved
      interaction presents an excellent opportunity for antiviral targeting. Here we
      report a group of pentavalent antimony-containing small molecule compounds, NSC
      13778 (molecular weight, 319) and its analogs, which exert a potent anti-HIV
      activity. These compounds block the entry of X4-, R5-, and X4/R5-tropic HIV-1
      strains into CD4(+) cells but show little or no activity in CD4-negative cells or
      against vesicular stomatitis virus-G pseudotyped virions. The compounds compete
      with gp120 for binding to CD4: either immobilized on a solid phase (soluble CD4)
      or on the T-cell surface (native CD4 receptor) as determined by a competitive
      gp120 capture enzyme-linked immunosorbent assay or flow cytometry. NSC 13778
      binds to an N-terminal two-domain CD4 protein, D1/D2 CD4, immobilized on a
      surface plasmon resonance sensor chip, and dose dependently reduces the emission
      intensity of intrinsic tryptophan fluorescence of D1/D2 CD4, which contains two
      of the three tryptophan residues in the gp120-binding domain. Furthermore, T
      cells incubated with the compounds alone show decreased reactivity to anti-CD4
      monoclonal antibodies known to recognize the gp120-binding site. In contrast to
      gp120-binders that inhibit gp120-CD4 interaction by binding to gp120, these
      compounds appear to disrupt gp120-CD4 contact by targeting the specific gp120
      binding domain of CD4. NSC 13778 may represent a prototype of a new class of HIV
      1 entry inhibitors that can break into the gp120-CD4 interface and mask the gp120
      binding site on the CD4 molecules, effectively repelling incoming virions.

PMID- 15857998
TI  - Structural basis for the physiological temperature dependence of the association
      of VP16 with the cytoplasmic tail of herpes simplex virus glycoprotein H.
AB  - Critical events in the life cycle of herpes simplex virus (HSV) are the binding
      of cytoplasmic capsids to cellular organelles and subsequent envelopment. Work
      from several laboratories suggests that these events occur as a result of a
      network of partially redundant interactions among the capsid surface, tegument
      components, and cytoplasmic tails of virally encoded glycoproteins. Consistent
      with this model, we previously showed that tegument protein VP16 can specifically
      interact with the cytoplasmic tail of envelope protein gH in vitro and in vivo
      when fused to glutathione S-transferase and to green fluorescent protein,
      respectively. In both instances, this association was strikingly temperature
      dependent: binding occurred only at 37 degrees C and not at lower temperatures.
      Here we demonstrate that virally expressed full-length gH and VP16 can be
      coimmunoprecipitated from HSV-infected cells and that this association is also
      critically dependent upon the physiological temperature. To investigate the basis
      of this temperature requirement, we performed one- and two-dimensional nuclear
      magnetic resonance spectroscopy on peptides with the sequence of the gH tail. We
      found that the gH tail is disorganized at temperatures permissive for binding but
      becomes structured at lower temperatures. Furthermore, a mutated tail unable to
      adopt this rigid conformation binds VP16 even at 4 degrees C. We hypothesize that
      the gH tail is unstructured under physiological conditions in order to maximize
      the number of potential tegument partners with which it may associate. Being
      initially disordered, the gH tail may adopt one of several induced conformations
      as it associates with VP16 or alternative components of the tegument, maximizing
      redundancy during particle assembly.

PMID- 15857999
TI  - Infectious bronchitis virus 3a protein localizes to a novel domain of the smooth
      endoplasmic reticulum.
AB  - All coronaviruses possess small open reading frames (ORFs) between structural
      genes that have been hypothesized to play important roles in pathogenesis.
      Infectious bronchitis virus (IBV) ORF 3a is one such gene. It is highly conserved
      among group 3 coronaviruses, suggesting that it has an important function in
      infection. IBV 3a protein is expressed in infected cells but is not detected in
      virions. Sequence analysis predicted that IBV 3a was a membrane protein; however,
      only a fraction behaved like an integral membrane protein. Microscopy and
      immunoprecipitation studies demonstrated that IBV 3a localized to the cytoplasm
      in a diffuse pattern as well as in sharp puncta in both infected and transfected
      cells. These puncta did not overlap cellular organelles or other punctate
      structures. Confocal microscopy demonstrated that IBV 3a puncta lined up along
      smooth endoplasmic reticulum (ER) tubules and, in a significant number of
      instances, were partially surrounded by these tubules. Our results suggest that
      IBV 3a is partially targeted to a novel domain of the smooth ER.

PMID- 15858000
TI  - Cellular localization and antigenic characterization of crimean-congo hemorrhagic
      fever virus glycoproteins.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Nairovirus
      of the family Bunyaviridae, causes severe disease with high rates of mortality in
      humans. The CCHFV M RNA segment encodes the virus glycoproteins G(N) and G(C). To
      understand the processing and intracellular localization of the CCHFV
      glycoproteins as well as their neutralization and protection determinants, we
      produced and characterized monoclonal antibodies (MAbs) specific for both G(N)
      and G(C). Using these MAbs, we found that G(N) predominantly colocalized with a
      Golgi marker when expressed alone or with G(C), while G(C) was transported to the
      Golgi apparatus only in the presence of G(N). Both proteins remained endo-beta-N
      acetylglucosaminidase H sensitive, indicating that the CCHFV glycoproteins are
      most likely targeted to the cis Golgi apparatus. Golgi targeting information
      partly resides within the G(N) ectodomain, because a soluble version of G(N)
      lacking its transmembrane and cytoplasmic domains also localized to the Golgi
      apparatus. Coexpression of soluble versions of G(N) and G(C) also resulted in
      localization of soluble G(C) to the Golgi apparatus, indicating that the
      ectodomains of these proteins are sufficient for the interactions needed for
      Golgi targeting. Finally, the mucin-like and P35 domains, located at the N
      terminus of the G(N) precursor protein and removed posttranslationally by
      endoproteolysis, were required for Golgi targeting of G(N) when it was expressed
      alone but were dispensable when G(C) was coexpressed. In neutralization assays on
      SW-13 cells, MAbs to G(C), but not to G(N), prevented CCHFV infection. However,
      only a subset of G(C) MAbs protected mice in passive-immunization experiments,
      while some nonneutralizing G(N) MAbs efficiently protected animals from a lethal
      CCHFV challenge. Thus, neutralization of CCHFV likely depends not only on the
      properties of the antibody, but on host cell factors as well. In addition,
      nonneutralizing antibody-dependent mechanisms, such as antibody-dependent cell
      mediated cytotoxicity, may be involved in the in vivo protection seen with the
      MAbs to G(C).

PMID- 15858001
TI  - The locus encompassing the latency-associated transcript of herpes simplex virus
      type 1 interferes with and delays interferon expression in productively infected
      neuroblastoma cells and trigeminal Ganglia of acutely infected mice.
AB  - The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) is
      the only abundant viral transcript expressed in latently infected neurons. LAT
      inhibits apoptosis, suggesting that it regulates latency by promoting the
      survival of infected neurons. The LAT locus also contains a newly described gene
      (AL), which is antisense to LAT and partially overlaps LAT encoding sequences.
      When human (SK-N-SH) or mouse (neuro-2A) neuroblastoma cells were infected with a
      virus that does not express LAT or AL gene products (dLAT2903), beta interferon
      (IFN-beta) and IFN-alpha RNA expression was detected earlier relative to the same
      cells infected with HSV-1 strains that express LAT and AL. Infection of neuro-2A
      cells with dLAT2903 also led to higher levels of IFN-beta promoter activity than
      in cells infected with wild-type (wt) HSV-1. In contrast, IFN RNA expression was
      the same when human lung fibroblasts were infected with dLAT2903 or wt HSV-1.
      When BALB/c mice were infected with dLAT2903, IFN-alpha and IFN-beta RNA
      expression was readily detected in trigeminal ganglia (TG) 4 days after
      infection. These transcripts were not detected in TG of mice infected with wt HSV
      1 or dLAT2903R (marker-rescued dLAT2903) until 6 days postinfection. When TG
      single-cell suspensions from infected BALB/c mice were prepared and incubated in
      vitro with wt HSV-1 as a source of antigen, TG cultures prepared from mice
      infected with dLAT2903 produced and secreted higher levels of IFN protein than wt
      HSV-1 or dLAT2903R. Collectively, these studies suggest that the LAT locus
      interferes with and delays IFN expression.

PMID- 15858002
TI  - The polypyrimidine tract binding protein is required for efficient picornavirus
      gene expression and propagation.
AB  - Mammalian host factors required for efficient viral gene expression and
      propagation have been often recalcitrant to genetic analysis. A case in point is
      the function of cellular factors that trans-activate internal ribosomal entry
      site (IRES)-driven translation, which is operative in many positive-stranded RNA
      viruses, including all picornaviruses. These IRES trans-acting factors have been
      elegantly studied in vitro, but their in vivo importance for viral gene
      expression and propagation has not been widely confirmed experimentally. Here we
      use RNA interference to deplete mammalian cells of one such factor, the
      polypyrimidine tract binding protein, and test its requirement in picornavirus
      gene expression and propagation. Depletion of the polypyrimidine tract binding
      protein resulted in a marked delay of particle propagation and significantly
      decreased synthesis and accumulation of viral proteins of poliovirus and
      encephalomyocarditis virus. These effects could be partially restored by
      expression of an RNA interference-resistant exogenous polypyrimidine tract
      binding protein. These data indicate a critical role for the polypyrimidine tract
      binding protein in picornavirus gene expression and strongly suggest a
      requirement for efficient IRES-dependent translation.

PMID- 15858003
TI  - Comparative host gene transcription by microarray analysis early after infection
      of the Huh7 cell line by severe acute respiratory syndrome coronavirus and human
      coronavirus 229E.
AB  - The pathogenesis of severe acute respiratory syndrome-associated coronavirus
      (SARS-CoV) at the cellular level is unclear. No human cell line was previously
      known to be susceptible to both SARS-CoV and other human coronaviruses. Huh7
      cells were found to be susceptible to both SARS-CoV, associated with SARS, and
      human coronavirus 229E (HCoV-229E), usually associated with the common cold.
      Highly lytic and productive rates of infections within 48 h of inoculation were
      reproducible with both viruses. The early transcriptional profiles of host cell
      response to both types of infection at 2 and 4 h postinoculation were determined
      by using the Affymetrix HG-U133A microarray (about 22,000 genes). Much more
      perturbation of cellular gene transcription was observed after infection by SARS
      CoV than after infection by HCoV-229E. Besides the upregulation of genes
      associated with apoptosis, which was exactly opposite to the previously reported
      effect of SARS-CoV in a colonic carcinoma cell line, genes related to
      inflammation, stress response, and procoagulation were also upregulated. These
      findings were confirmed by semiquantitative reverse transcription-PCR, reverse
      transcription-quantitative PCR for mRNA of genes, and immunoassays for some
      encoded proteins. These transcriptomal changes are compatible with the
      histological changes of pulmonary vasculitis and microvascular thrombosis in
      addition to the diffuse alveolar damage involving the pneumocytes.

PMID- 15858004
TI  - Carboxyl-proximal regions of reovirus nonstructural protein muNS necessary and
      sufficient for forming factory-like inclusions.
AB  - Mammalian orthoreoviruses are believed to replicate in distinctive, cytoplasmic
      inclusion bodies, commonly called viral factories or viroplasms. The viral
      nonstructural protein muNS has been implicated in forming the matrix of these
      structures, as well as in recruiting other components to them for putative roles
      in genome replication and particle assembly. In this study, we sought to identify
      the regions of muNS that are involved in forming factory-like inclusions in
      transfected cells in the absence of infection or other viral proteins. Sequences
      in the carboxyl-terminal one-third of the 721-residue muNS protein were linked to
      this activity. Deletion of as few as eight residues from the carboxyl terminus of
      muNS resulted in loss of inclusion formation, suggesting that some portion of
      these residues is required for the phenotype. A region spanning residues 471 to
      721 of muNS was the smallest one shown to be sufficient for forming factory-like
      inclusions. The region from positions 471 to 721 (471-721 region) includes both
      of two previously predicted coiled-coil segments in muNS, suggesting that one or
      both of these segments may also be required for inclusion formation. Deletion of
      the more amino-terminal one of the two predicted coiled-coil segments from the
      471-721 region resulted in loss of the phenotype, although replacement of this
      segment with Aequorea victoria green fluorescent protein, which is known to
      weakly dimerize, largely restored inclusion formation. Sequences between the two
      predicted coiled-coil segments were also required for forming factory-like
      inclusions, and mutation of either one His residue (His570) or one Cys residue
      (Cys572) within these sequences disrupted the phenotype. The His and Cys residues
      are part of a small consensus motif that is conserved across muNS homologs from
      avian orthoreoviruses and aquareoviruses, suggesting this motif may have a common
      function in these related viruses. The inclusion-forming 471-721 region of muNS
      was shown to provide a useful platform for the presentation of peptides for
      studies of protein-protein association through colocalization to factory-like
      inclusions in transfected cells.

PMID- 15858005
TI  - Relocalization of the Mre11-Rad50-Nbs1 complex by the adenovirus E4 ORF3 protein
      is required for viral replication.
AB  - Adenovirus replication is controlled by the relocalization or modification of
      nuclear protein complexes, including promyelocytic leukemia protein (PML) nuclear
      domains and the Mre11-Rad50-Nbs1 (MRN) DNA damage machinery. In this study, we
      demonstrated that the E4 ORF3 protein effects the relocalization of both PML and
      MRN proteins to similar structures within the nucleus at early times after
      infection. These proteins colocalize with E4 ORF3. Through the analysis of
      specific viral mutants, we found a direct correlation between MRN reorganization
      at early times after infection and the establishment of viral DNA replication
      domains. Further, the reorganization of MRN components may be uncoupled from the
      ability of E4 ORF3 to rearrange PML. At later stages of infection, components of
      the MRN complex disperse within the nucleus, Nbs1 is found within viral
      replication centers, Rad50 remains localized with E4 ORF3, and Mre11 is degraded.
      The importance of viral regulation of the MRN complex is underscored by the
      complementation of E4 mutant viruses in cells that lack Mre11 or Nbs1 activity.
      These results illustrate the importance of nuclear organization in virus growth
      and suggest that E4 ORF3 regulates activities in both PML nuclear bodies and the
      MRN complex to stimulate the viral replication program.

PMID- 15858006
TI  - Unusual topological arrangement of structural motifs in the baboon reovirus
      fusion-associated small transmembrane protein.
AB  - Select members of the Reoviridae are the only nonenveloped viruses known to
      induce syncytium formation. The fusogenic orthoreoviruses accomplish cell-cell
      fusion through a distinct class of membrane fusion-inducing proteins referred to
      as the fusion-associated small transmembrane (FAST) proteins. The p15 membrane
      fusion protein of baboon reovirus is unique among the FAST proteins in that it
      contains two hydrophobic regions (H1 and H2) recognized as potential
      transmembrane (TM) domains, suggesting a polytopic topology. However, detailed
      topological analysis of p15 indicated only the H1 domain is membrane spanning. In
      the absence of an N-terminal signal peptide, the H1 TM domain serves as a reverse
      signal-anchor to direct p15 membrane insertion and a bitopic
      N(exoplasmic)/C(cytoplasmic) topology. This topology results in the translocation
      of the smallest ectodomain ( approximately 20 residues) of any known viral fusion
      protein, with the majority of p15 positioned on the cytosolic side of the
      membrane. Mutagenic analysis indicated the unusual presence of an N-terminal
      myristic acid on the small p15 ectodomain is essential to the fusion process.
      Furthermore, the only other hydrophobic region (H2) present in p15, aside from
      the TM domain, is located within the endodomain. Consequently, the p15 ectodomain
      is devoid of a fusion peptide motif, a hallmark feature of membrane fusion
      proteins. The exceedingly small, myristoylated ectodomain and the unusual
      topological distribution of structural motifs in this nonenveloped virus membrane
      fusion protein necessitate alternate models of protein-mediated membrane fusion.

PMID- 15858007
TI  - Biochemical characterization of rous sarcoma virus MA protein interaction with
      membranes.
AB  - The MA domain of retroviral Gag proteins mediates association with the host cell
      membrane during assembly. The biochemical nature of this interaction is not well
      understood. We have used an in vitro flotation assay to directly measure Rous
      sarcoma virus (RSV) MA-membrane interaction in the absence of host cell factors.
      The association of purified MA and MA-containing proteins with liposomes of
      defined composition was electrostatic in nature and depended upon the presence of
      a biologically relevant concentration of negatively charged lipids. A mutant MA
      protein known to be unable to promote Gag membrane association and budding in
      vivo failed to bind to liposomes. These results were supported by computational
      modeling. The intrinsic affinity of RSV MA for negatively charged membranes
      appears insufficient to promote efficient plasma membrane binding during
      assembly. However, an artificially dimerized form of MA bound to liposomes by at
      least an order of magnitude more tightly than monomeric MA. This result suggests
      that the clustering of MA domains, via Gag-Gag interactions during virus
      assembly, drives membrane association in vivo.

PMID- 15858008
TI  - Capsid protein synthesis from replicating RNA directs specific packaging of the
      genome of a multipartite, positive-strand RNA virus.
AB  - Flock house virus (FHV) is a bipartite, positive-strand RNA insect virus that
      encapsidates its two genomic RNAs in a single virion. It provides a convenient
      model system for studying the principles underlying the copackaging of
      multipartite viral RNA genomes. In this study, we used a baculovirus expression
      system to determine if the uncoupling of viral protein synthesis from RNA
      replication affected the packaging of FHV RNAs. We found that neither RNA1 (which
      encodes the viral replicase) nor RNA2 (which encodes the capsid protein) were
      packaged efficiently when capsid protein was supplied in trans from
      nonreplicating RNA. However, capsid protein synthesized in cis from replicating
      RNA2 packaged RNA2 efficiently in the presence and absence of RNA1. These results
      demonstrated that capsid protein translation from replicating RNA2 is required
      for specific packaging of the FHV genome. This type of coupling between genome
      replication and translation and RNA packaging has not been observed previously.
      We hypothesize that RNA2 replication and translation must be spatially
      coordinated in FHV-infected cells to facilitate retrieval of the viral RNAs for
      encapsidation by newly synthesized capsid protein. Spatial coordination of RNA
      and capsid protein synthesis may be key to specific genome packaging and assembly
      in other RNA viruses.

PMID- 15858009
TI  - Impact of viral factors on very early in vivo replication profiles in simian
      immunodeficiency virus SIVagm-infected African green monkeys.
AB  - To better understand which factors govern the levels of viral loads in early
      lentiviral infections of primates, we developed a model that allows
      distinguishing between the influences of host and viral factors on viremia.
      Herein we report that two species of African green monkeys (Chlorocebus sabaeus
      and C. pygerythrus) infected with their respective wild-type simian
      immunodeficiency virus SIVagm viruses (SIVagm.sab92018 and SIVagm.ver644)
      consistently showed reproducible differences in viremia during primary infection
      but not at later stages of infection. Cross-infections of SIVagm.sab92018 and
      SIVagm.ver644 into, respectively, C. pygerythrus and C. sabaeus revealed that the
      dynamics of viral replication during primary infection were dependent on the
      viral strain used for the infection but not on the host. Hence, the kinetics of
      SIVagm.sab92018 and SIVagm.ver644 were similar in both sabaeus and vervet
      animals, indicating that the difference in viremia levels between the two groups
      during the early phase of infection was not associated with the host. Coreceptor
      usage for these two strains showed a larger coreceptor repertoire for
      SIVagm.sab92018, which is able to efficiently use CXCR4 in addition to CCR5, than
      for SIVagm.ver644, which showed a classical CCR5 coreceptor usage pattern. These
      differences could not be explained by different charges of the V3 loop for
      SIVagm.sab92018 and for SIVagm.ver644. In conclusion, our study showed that the
      extent of virus replication during the primary infection is primarily dependent
      on viral determinants.

PMID- 15858010
TI  - Epitope-mapping studies define two major neutralization sites on the vaccinia
      virus extracellular enveloped virus glycoprotein B5R.
AB  - Vaccinia extracellular enveloped virus (EEV) is critical for cell-to-cell and
      long-range virus spread both in vitro and in vivo. The B5R gene encodes an EEV
      specific type I membrane protein that is essential for efficient EEV formation.
      The majority of the B5R ectodomain consists of four domains with homology to
      short consensus repeat domains followed by a stalk. Previous studies have shown
      that polyclonal antibodies raised against the B5R ectodomain inhibit EEV
      infection. In this study, our goal was to elucidate the antigenic structure of
      B5R and relate this to its function. To do this, we produced multimilligram
      quantities of vaccinia virus B5R as a soluble protein [B5R(275t)] using a
      baculovirus expression system. We then selected and characterized a panel of 26
      monoclonal antibodies (MAbs) that recognize B5R(275t). Five of these MAbs
      neutralized EEV and inhibited comet formation. Two other MAbs were able only to
      neutralize EEV, while five others were able only to inhibit comet formation. This
      suggests that the EEV neutralization and comet inhibition assays measure
      different viral functions and that at least two different antigenic sites on B5R
      are important for these activities. We further characterized the MAbs and the
      antigenic structure of B5R(275t) by peptide mapping and by reciprocal MAb
      blocking studies using biosensor analysis. The epitopes recognized by
      neutralizing MAbs were localized to SCR1-SCR2 and/or the stalk of B5R(275t).
      Furthermore, the peptide and blocking data support the concept that SCR1 and the
      stalk may be in juxtaposition and may be part of the same functional domain.

PMID- 15858011
TI  - Induction of long-term protective antiviral endogenous immune response by short
      neutralizing monoclonal antibody treatment.
AB  - Long-term immune control of viral replication still remains a major challenge in
      retroviral diseases. Several monoclonal antibodies (MAbs) have already shown
      antiviral activities in vivo, including in the clinic but their effects on the
      immune system of treated individuals are essentially unknown. Using the lethal
      neurodegeneration induced in mice upon infection of neonates by the FrCas(E)
      retrovirus as a model, we report here that transient treatment by a neutralizing
      MAb shortly after infection can, after an immediate antiviral effect, favor the
      development of a strong protective host immune response containing viral
      propagation long after the MAb has disappeared. In vitro virus neutralization-
      and complement-mediated cell lysis assays, as well as in vivo viral challenges
      and serum transfer experiments, indicate a clear and essential contribution of
      the humoral response to antiviral protection. Our observation may have important
      therapeutic consequences as it suggests that short antibody-based therapies early
      after infection should be considered, at least in the case of maternally infected
      infants, as adjunctive treatment strategies against human immunodeficiency virus,
      not only for a direct effect on the viral load but also for favoring the
      emergence of an endogenous antiviral immune response.

PMID- 15858013
TI  - New antiviral pathway that mediates hepatitis C virus replicon interferon
      sensitivity through ADAR1.
AB  - While many clinical hepatitis C virus (HCV) infections are resistant to alpha
      interferon (IFN-alpha) therapy, subgenomic in vitro self-replicating HCV RNAs
      (HCV replicons) are characterized by marked IFN-alpha sensitivity. IFN-alpha
      treatment of replicon-containing cells results in a rapid loss of viral RNA via
      translation inhibition through double-stranded RNA-activated protein kinase (PKR)
      and also through a new pathway involving RNA editing by an adenosine deaminase
      that acts on double-stranded RNA (ADAR1). More than 200 genes are induced by IFN
      alpha, and yet only a few are attributed with an antiviral role. We show that
      inhibition of both PKR and ADAR1 by the addition of adenovirus-associated RNA
      stimulates replicon expression and reduces the amount of inosine recovered from
      RNA in replicon cells. Small inhibitory RNA, specific for ADAR1, stimulated the
      replicon 40-fold, indicating that ADAR1 has a role in limiting replication of the
      viral RNA. This is the first report of ADAR's involvement in a potent antiviral
      pathway and its action to specifically eliminate HCV RNA through adenosine to
      inosine editing. These results may explain successful HCV replicon clearance by
      IFN-alpha in vitro and may provide a promising new therapeutic strategy for HCV
      as well as other viral infections.

PMID- 15858012
TI  - Genetic determinants of cell type-specific poliovirus propagation in HEK 293
      cells.
AB  - The ability of poliovirus to propagate in neuronal cells can be reduced by
      introducing appropriate nucleotide substitutions into the viral genome. Specific
      mutations scattered throughout the poliovirus genome yielded the live attenuated
      vaccine strains of poliovirus. Neuron-specific propagation deficits of the Sabin
      strains are partially encrypted within a confined region of the internal
      ribosomal entry site (IRES), which carries attenuating point mutations in all
      three serotypes. Recently, high levels of neurovirulence attenuation were
      achieved with genetically engineered polioviruses containing heterologous IRES
      elements. This is exemplified with poliovirus recombinants replicating under
      control of a human rhinovirus type 2 (HRV2) IRES element. We have carried out
      experiments delineating the genetic basis for neuronal IRES function. Neuronal
      dysfunction of the HRV2 IRES is determined mainly by IRES stem-loop domain V, the
      locus for attenuating point mutations within the Sabin strains. Neuronal
      incompetence associated with HRV2 IRES domain V is substantially more pronounced
      than that observed with the attenuating IRES point mutation of the Sabin serotype
      1 vaccine strain. Mix-and-match recombination of polio and HRV2 IRES domain V
      suggests that the attenuation phenotype correlates with overall structural
      features rather than primary sequence. Our experiments have identified HEK 293
      cells as a novel system for the study of neuron-specific replication phenotypes
      of poliovirus. This cell line, originally derived from embryonic human kidney,
      has recently been described to display neuronal characteristics. We report
      propagation properties in HEK 293 cells for poliovirus recombinants with
      attenuated neurovirulence in experimental animals that corroborate this
      observation.

PMID- 15858014
TI  - Distinct mechanisms of CD4+ and CD8+ T-cell activation and bystander apoptosis
      induced by human immunodeficiency virus type 1 virions.
AB  - Apoptosis of uninfected bystander T cells contributes to T-cell depletion during
      human immunodeficiency virus type 1 (HIV-1) infection. HIV-1 envelope/receptor
      interactions and immune activation have been implicated as contributors to
      bystander apoptosis. To better understand the relationship between T-cell
      activation and bystander apoptosis during HIV-1 pathogenesis, we investigated the
      effects of the highly cytopathic CXCR4-tropic HIV-1 variant ELI6 on primary
      CD4(+) and CD8(+) T cells. Infection of primary T-cell cultures with ELI6 induced
      CD4(+) T-cell depletion by direct cell lysis and bystander apoptosis. Exposure of
      primary CD4(+) and CD8(+) T cells to nonreplicating ELI6 virions induced
      bystander apoptosis through a Fas-independent mechanism. Bystander apoptosis of
      CD4(+) T cells required direct contact with virions and Env/CXCR4 binding. In
      contrast, the apoptosis of CD8(+) T cells was triggered by a soluble factor(s)
      secreted by CD4(+) T cells. HIV-1 virions activated CD4(+) and CD8(+) T cells to
      express CD25 and HLA-DR and preferentially induced apoptosis in CD25(+)HLA-DR(+)
      T cells in a CXCR4-dependent manner. Maximal levels of binding, activation, and
      apoptosis were induced by virions that incorporated MHC class II and B7-2 into
      the viral membrane. These results suggest that nonreplicating HIV-1 virions
      contribute to chronic immune activation and T-cell depletion during HIV-1
      pathogenesis by activating CD4(+) and CD8(+) T cells, which then proceed to die
      via apoptosis. This mechanism may represent a viral immune evasion strategy to
      increase viral replication by activating target cells while killing immune
      effector cells that are not productively infected.

PMID- 15858015
TI  - Discontinuous subgenomic RNA synthesis in arteriviruses is guided by an RNA
      hairpin structure located in the genomic leader region.
AB  - Nidoviruses produce an extensive 3'-coterminal nested set of subgenomic (sg)
      mRNAs, which are used to express structural proteins and sometimes accessory
      proteins. In arteriviruses and coronaviruses, these mRNAs contain a common 5'
      leader sequence, derived from the genomic 5' end. The joining of the leader
      sequence to different segments derived from the 3'-proximal part of the genome
      (mRNA bodies) presumably involves a unique mechanism of discontinuous minus
      strand RNA synthesis in which base pairing between sense and antisense
      transcription-regulating sequences (TRSs) plays an essential role. The leader TRS
      is present in the loop of a hairpin structure that functions in sg mRNA
      synthesis. In this study, the minimal sequences in the 5'-proximal region of the
      Equine arteritis virus genome that are required for sg RNA synthesis were
      delimited through mutagenesis. A full-length cDNA clone was engineered in which
      this domain was duplicated, allowing us to make mutations and monitor their
      effects on sg RNA synthesis without seriously affecting genome replication and
      translation. The leader TRS present in the duplicated sequence was used and
      yielded novel sg mRNAs with significantly extended leaders. Our combined findings
      suggest that the leader TRS hairpin (LTH) and its immediate flanking sequences
      are essential for efficient sg RNA synthesis and form an independent functional
      entity that could be moved 300 nucleotides downstream of its original position in
      the genome. We hypothesize that a conformational switch in the LTH region
      regulates the role of the 5'-proximal region of the arterivirus genome in
      subgenomic RNA synthesis.

PMID- 15858016
TI  - Sequence variability, gene structure, and expression of full-length human
      endogenous retrovirus H.
AB  - Recently, we identified and classified 926 human endogenous retrovirus H (HERV-H)
      like proviruses in the human genome. In this paper, we used the information to,
      in silico, reconstruct a putative ancestral HERV-H. A calculated consensus
      sequence was nearly open in all genes. A few manual adjustments resulted in a
      putative 9-kb HERV-H provirus with open reading frames (ORFs) in gag, pro, pol,
      and env. Long terminal repeats (LTRs) differed by 1.1%, indicating proximity to
      an integration event. The gag ORF was extended upstream of the normal
      myristylation start site. There was a long leader (including a "pre-gag" ORF)
      region positioned like the N terminus of murine leukemia virus (MLV) "glyco-Gag,"
      potentially encoding a proline- and serine-rich domain remotely similar to MLV
      pp12. Another ORF, starting inside the 5' LTR, had no obvious similarity to known
      protein domains. Unlike other hitherto described gammaretroviruses, the
      reconstructed Gag had two zinc finger motifs. Alternative splicing of sequences
      related to the HERV-H consensus was confirmed using dbEST data. env transcripts
      were most prevalent in colon tumors, but also in normal testis. We found no
      evidence for full length env transcripts in the dbEST. HERV-H had a markedly
      skewed nucleotide composition, disfavoring guanine and favoring cytidine. We
      conclude that the HERV-H consensus shared a gene arrangement common to
      gammaretroviruses with gag separated by stop codon from pro-pol in the same
      reading frame, while env resides in another reading frame. There was also
      alternative splicing. HERV-H consensus yielded new insights in gammaretroviral
      evolution and will be useful as a model in studies on expression and function.

PMID- 15858017
TI  - Analysis of the contribution of reverse transcriptase and integrase proteins to
      retroviral RNA dimer conformation.
AB  - All retroviruses contain two copies of genomic RNA that are linked noncovalently.
      The dimeric RNA of human immunodeficiency virus type 1 (HIV-1) undergoes
      rearrangement during virion maturation, whereby the dimeric RNA genome assumes a
      more stable conformation. Previously, we have shown that the packaging of the HIV
      1 polymerase (Pol) proteins reverse transcriptase (RT) and integrase (IN) is
      essential for the generation of the mature RNA dimer conformation. Analysis of
      HIV-1 mutants that are defective in processing of Pol showed that these mutant
      virions contained altered dimeric RNA conformation, indicating that the mature
      RNA dimer conformation in HIV-1 requires the correct proteolytic processing of
      Pol. The HIV-1 Pol proteins are multimeric in their mature enzymatically active
      forms; RT forms a heterodimer, and IN appears to form a homotetramer. Using RT
      and IN multimerization defective mutants, we have found that dimeric RNA from
      these mutant virions has the same stability and conformation as wild-type RNA
      dimers, showing that the mature enzymatically active RT and IN proteins are
      dispensable for the generation of mature RNA dimer conformation. This also
      indicated that formation of the mature RNA dimer structure occurs prior to RT or
      IN maturation. We have also investigated the requirement of Pol for RNA
      dimerization in both Mason-Pfizer monkey virus (M-PMV) and Moloney murine
      leukemia virus (MoMuLV) and found that in contrast to HIV-1, Pol is dispensable
      for RNA dimer maturation in M-PMV and MoMuLV, demonstrating that the requirement
      of Pol in retroviral RNA dimer maturation is not conserved among all
      retroviruses.

PMID- 15858018
TI  - Compartmentalization of hepatitis C virus genotypes between plasma and peripheral
      blood mononuclear cells.
AB  - Differences in hepatitis C virus (HCV) variants of the highly conserved 5'
      untranslated region (UTR) have been observed between plasma and peripheral blood
      mononuclear cells (PBMC). The prevalence and the mechanisms of this
      compartmentalization are unknown. Plasma and PBMC HCV variants were compared by
      single-strand conformation polymorphism (SSCP) and by cloning or by genotyping
      with a line probe assay (LiPA) in 116 chronically infected patients, including 44
      liver transplant recipients. SSCP patterns differed between compartments in
      43/109 analyzable patients (39%). Differences were significantly more frequent in
      patients with transplants (21/38 [55%] versus 22/71 [31%]; P < 0.01) and in those
      who acquired HCV through multiple transfusions before 1991 (15/20; 75%) or
      through drug injection (16/31; 52%) than in those infected through an unknown
      route (7/29; 24%) or through a single transfusion (5/29; 17%; P < 0.001). Cloning
      of the 5' UTR, LiPA analysis, and nonstructural region 5B sequencing revealed
      different genotypes in the two compartments from 10 patients (9%). In nine
      patients, the genotype detected in PBMC was not detected in plasma and was weak
      or undetectable in the liver in three cases. This genotypic compartmentalization
      persisted for years in three patients and after liver transplantation in two. The
      present study shows that a significant proportion of HCV-infected subjects harbor
      in their PBMC highly divergent variants which were likely acquired through
      superinfections.

PMID- 15858019
TI  - Stimulation of poliovirus synthesis in a HeLa cell-free in vitro translation-RNA
      replication system by viral protein 3CDpro.
AB  - The plus-strand RNA genome of poliovirus serves three distinct functions in the
      life cycle of the virus. The RNA is translated and then replicated, and finally
      the progeny RNAs are encapsidated. These processes can be faithfully reproduced
      in a HeLa cell-free in vitro translation-RNA replication system that produces
      viable poliovirus. We have previously observed a stimulation of virus synthesis
      when an mRNA, encoding protein 3CD(pro), is added to the translation-RNA
      replication reactions of poliovirus RNA. Our aim in these experiments was to
      further define the factors that affect the stimulatory activity of 3CD(pro) in
      virus synthesis. We observed that purified 3CD(pro) protein also enhances virus
      synthesis by about 100-fold but has no effect on the translation of the
      polyprotein. Optimal stimulation is observed only when 3CD(pro) is present early
      in the incubation period. The stimulation, however, is abolished by a mutation
      either in the RNA binding domain of 3CD(pro), 3C(pro)R84S/I86A, or by each of two
      groups of complementary mutations R455A/R456A and D339A/S341A/D349A at interface
      I in the 3D(pol) domain of 3CD(pro). Surprisingly, virus synthesis is strongly
      inhibited by the addition of both 3C(pro) and 3CD(pro) at the beginning of
      incubation. We also examined the effect of other viral or cellular proteins on
      virus synthesis in the in vitro system. No enhancement of virus synthesis
      occurred with viral proteins 3BC, 3ABC, 3BCD, 3D(pol), and 3C(pro) or with
      cellular protein PCBP2. These results suggest that 3CD(pro) has to be present in
      the reaction at the time the replication complexes are assembled and that both
      the 3C(pro) and 3D(pol) domains of the protein are required for its activity that
      stimulates virus production.

PMID- 15858020
TI  - Immunization with the gene expressing woodchuck hepatitis virus nucleocapsid
      protein fused to cytotoxic-T-lymphocyte-associated antigen 4 leads to enhanced
      specific immune responses in mice and woodchucks.
AB  - A number of options are available to modify and improve DNA vaccines. An
      interesting approach to improve DNA vaccines is to fuse bioactive domains, like
      cytotoxic-T-lymphocyte-associated protein 4 (CTLA-4), to an antigen. Such fusion
      antigens are expressed in vivo and directed to immune cells by the specific
      bioactive domain and therefore possess great potential to induce and modulate
      antigen-specific immune responses. In the present study, we tested this new
      approach for immunomodulation against hepadnavirus infection in the woodchuck
      model. Plasmids expressing the nucleocapsid protein (WHcAg) and e antigen (WHeAg)
      of woodchuck hepatitis virus (WHV) alone or in fusion to the extracellular domain
      of woodchuck CTLA-4 and CD28 were constructed. Immunizations of mice with
      plasmids expressing WHcAg or WHeAg led to a specific immunoglobulin G2a (IgG2a)
      dominant antibody response. In contrast, fusions of WHcAg to CTLA-4 and CD28
      induced a specific antibody response with comparable levels of IgG1 and IgG2a.
      Furthermore, the specific IgG1 response to WHcAg/WHeAg developed immediately
      after a single immunization with the CTLA-4-WHcAg fusion. Woodchucks were
      immunized with plasmids expressing WHeAg or the CTLA-4-WHcAg fusion and
      subsequently challenged with WHV. CTLA-4-WHcAg showed an improved efficacy in
      induction of protective immune responses to WHV. In particular, the anti-WHsAg
      antibody response developed earlier after challenge in woodchucks that received
      immunizations with CTLA-4-WHcAg, consistent with the hypothesis that anti-WHs
      response is dependent on a Th cell response to WHcAg. In conclusion, the use of
      fusion genes represents a generally applicable strategy to improve DNA
      vaccination.

PMID- 15858022
TI  - Identification of domains in gag important for prototypic foamy virus egress.
AB  - Sequence motifs (L domains) have been described in viral structural proteins.
      Mutations in these lead to a defect at a late stage in virus assembly and
      budding. For several viruses, recruitment of an endosomal sorting complexes
      required for transport 1 subunit (Tsg101), a component of the class E vacuolar
      protein sorting (EVPS) machinery, is a prerequisite for virion budding. To effect
      this, Tsg101 interacts with the PT/SAP L domain. We have identified candidate L
      domain motifs, PSAP, PPPI, and YEIL, in the prototypic foamy virus (PFV) Gag
      protein, based on their homology to known viral L domains. Mutation of the PSAP
      and PPPI motifs individually reduced PFV egress, and their combined mutation had
      an additive effect. When PSAP was mutated, residual infectious PFV release was
      unaffected by dominant negative Vps4 (an ATPase involved in the final stages of
      budding), and sensitivity to dominant negative Tsg101 was dramatically reduced,
      suggesting that the PSAP motif functions as a conventional class E VPS-dependent
      L domain. Consistent with this notion, yeast two-hybrid analysis showed a PSAP
      motif-dependent interaction between PFV Gag and Tsg101. Surprisingly, PFV release
      which is dependent on the PPPI motif was Vps4-independent and was partially
      inhibited by dominant negative Tsg101, suggesting that PPPI functions by an
      unconventional mechanism to facilitate PFV egress. Mutation of the YEIL sequence
      completely abolished particle formation and also reduced the rate of Gag
      processing by the viral protease, suggesting that the integrity of YEIL is
      required at an assembly step prior to budding and YEIL is not acting as an L
      domain.

PMID- 15858023
TI  - An adenovirus type 5 (Ad5) amplicon-based packaging cell line for production of
      high-capacity helper-independent deltaE1-E2-E3-E4 Ad5 vectors.
AB  - Production of multiply deleted adenoviral (Ad) vectors with increased cloning
      capacity and reduced immunogenicity to adenovirus gene products requires the
      concomitant generation of efficient packaging cell lines. High expression levels
      of the complementing genes must be achieved in a coordinated fashion with viral
      replication. This is a particularly difficult task in light of the significant
      cytotoxicity displayed by adenoviral proteins. To this end, we developed a novel
      adenovirus-based amplicon with an Epstein-Barr virus origin of replication, Ad
      type 5 (Ad5) inverted terminal repeats, all Ad5 early region 2 (E2) genes, and
      the early region 4 (E4) open reading frame 6 (ORF6) under the control of a
      tetracycline-dependent promoter. The amplicon (pE2) was stably maintained in
      multiple copies in the nuclei of 293 cells stably expressing the Epstein-Barr
      virus nuclear antigen 1 (EBNA1) and allowed replication as a linear DNA upon
      induction of E2 and ORF6 gene expression. A stable cell line (2E2) was generated
      by introducing pE2 into 293EBNATet cells expressing the tetracycline-dependent
      transcriptional silencer and the reverse Tet transactivator (rtTA2). Upon
      induction with doxicycline, 2E2 cells produced higher levels of polymerase,
      precursor terminal protein (pTP), and DNA binding protein than noninduced 2E2
      cells infected with first-generation Ad5 vector and supported efficient
      amplification of a multiply deleted Ad5 vector lacking E1, E2, E3, and E4 genes
      (Ad5DeltaE(1-4)). The high cloning capacity of Ad5DeltaE(1-4) (up to 12.6 kb) was
      exploited to construct a vector encoding the entire hepatitis C virus (HCV)
      polyprotein. Infection of HeLa cells by the resulting vector showed high levels
      of correctly processed HCV proteins.

PMID- 15858021
TI  - The Nef-mediated AIDS-like disease of CD4C/human immunodeficiency virus
      transgenic mice is associated with increased Fas/FasL expression on T cells and T
      cell death but is not prevented in Fas-, FasL-, tumor necrosis factor receptor 1
      , or interleukin-1beta-converting enzyme-deficient or Bcl2-expressing transgenic
      mice.
AB  - CD4(+)- and CD8(+)-T-cell death is a frequent immunological dysfunction
      associated with the development of human AIDS. We studied a murine model of AIDS,
      the CD4C/HIV transgenic (Tg) mouse model, to assess the importance of the
      apoptotic pathway in human immunodeficiency virus type 1 (HIV-1) pathogenesis. In
      these Tg mice, Nef is the major determinant of the disease and is expressed in
      immature and mature CD4(+) T cells and in cells of the macrophage/myeloid
      lineage. We report here a novel AIDS-like phenotype: enhanced death, most likely
      by apoptosis (as assessed by 7-aminoactinomycin D and annexin V/propidium iodide
      staining), of Tg thymic and peripheral CD4(+) and CD8(+) T cells. The Tg CD4(+)
      and CD8(+) T cells were also more susceptible to cell death after activation in
      vitro in mixed lymph node (LN) cultures. However, activation-induced cell death
      was not higher in Tg than in non-Tg-purified CD4(+) T cells. In addition,
      expression of Fas and FasL, assessed by flow cytometry, was increased in CD4(+)
      and CD8(+) T cells from Tg mice compared to that of non-Tg littermates. Despite
      the enhanced expression of Fas and FasL on Tg CD4(+) and CD8(+) T cells, Fas
      (lpr/lpr) and FasL (gld/gld) mutant CD4C/HIV Tg mice developed an AIDS-like
      disease indistinguishable from lpr/+ and gld/+ CD4C/HIV Tg mice, including loss
      of CD4(+) T cells. Similarly, CD4C/HIV Tg mice homozygous for mutations of two
      other genes implicated in cell death (interleukin-1beta-converting enzyme [ICE],
      tumor necrosis factor receptor 1 [TNFR-1]) developed similar AIDS-like disease as
      their respective heterozygous controls. Moreover, the double-Tg mice from a cross
      between the Bcl2/Wehi25 and CD4C/HIV Tg mice showed no major protection against
      disease. These results represent genetic evidence for the dispensable role of
      Fas, FasL, ICE, and TNFR-1 on the development of both T-cell loss and organ
      disease of these Tg mice. They also provide compelling evidence on the lack of
      protection by Bcl2 against Tg CD4(+)-T-cell death. In view of the high
      resemblance between numerous phenotypes observed in the CD4C/HIV Tg mice and in
      human AIDS, our findings are likely to be relevant for the human disease.

PMID- 15858024
TI  - Use of confocal immunofluorescence microscopy to localize viral nonstructural
      proteins and potential sites of replication in pigs experimentally infected with
      foot-and-mouth disease virus.
AB  - Replication of foot-and-mouth disease virus in infected pig epithelium has been
      studied by immunofluorescence labeling of the viral nonstructural protein 3ABC
      and confocal microscopy. The results were correlated with viral RNA copy numbers
      in tissue samples from adjacent sites determined by reverse transcription-PCR (RT
      PCR). Lesion formation was seen in the tongues and coronary band epithelia of
      infected pigs 2 days after infection. Viral replication was observed in cells of
      the epithelium of the tongue and coronary band but not in the associated stromal
      cells. Infected epithelial cells were present in the stratum spinosum, away from
      the lesion, with small lesions formed above the basement membrane. Viral
      replication was markedly reduced in tongue epithelium by day 3 postinfection but
      remained apparent in the coronary band tissue up to 5 days postinfection. These
      results were confirmed by the RNA copy number determined by RT-PCR.

PMID- 15858025
TI  - Rhesus cytomegalovirus particles prevent activation of interferon regulatory
      factor 3.
AB  - One of the most important innate host defense mechanisms against viral infection
      is the induction of interferon (IFN)-stimulated genes (ISGs). Immediately upon
      entry, viruses activate interferon-regulatory factor 3 (IRF3), as well as nuclear
      factor kappaB (NF-kappaB), which transactivate a subset of ISGs, proinflammatory
      genes, as well as IFN genes. Most large DNA viruses exhibit countermeasures
      against induction of this response. However, whereas human cytomegalovirus (HCMV)
      inhibits IFN-dependent induction of ISGs, IFN-independent induction of ISGs is
      observed both in the presence and, even moreso, in the absence of viral gene
      expression. Rhesus CMV (RhCMV) is an emerging animal model for HCMV sharing
      important similarities in primary structure, epidemiology, and pathogenesis. To
      determine whether RhCMV would similarly induce ISGs, we performed DNA microarray
      and quantitative PCR analysis of ISG expression in rhesus fibroblasts infected
      with RhCMV or HCMV. In contrast to HCMV, however, RhCMV did not induce expression
      of ISGs or proinflammatory genes at any time after infection. Moreover,
      dimerization and nuclear accumulation of IRF3, readily observed in HCMV-infected
      cells, was absent from RhCMV-infected cells, whereas neither virus seemed to
      activate NFkappaB. RhCMV also blocked IRF3 activation by live or UV-inactivated
      HCMV, suggesting that RhCMV inhibits viral IRF3 activation and the resultant ISG
      induction with extraordinary efficiency. Since infection during inhibition of
      protein expression by cycloheximide or inactivation of viral gene expression by
      UV treatment did not trigger IRF3 activation or ISG expression by RhCMV, we
      conclude that RhCMV virions contain a novel inhibitor of IFN-independent viral
      induction of ISG expression by IRF3.

PMID- 15858026
TI  - Human immunodeficiency virus type 1 stimulates the expression and production of
      secretory leukocyte protease inhibitor (SLPI) in oral epithelial cells: a role
      for SLPI in innate mucosal immunity.
AB  - The innate immune response is a key barrier against pathogenic microorganisms
      such as human immunodeficiency virus type 1 (HIV-1). Because HIV-1 is rarely
      transmitted orally, we hypothesized that oral epithelial cells participate in the
      innate immune defense against this virus. We further hypothesized that secretory
      leukocyte protease inhibitor (SLPI), a 12-kDa mucosal antiviral protein, is a
      component of the host immune response to this virus. Here we demonstrated
      constitutive expression and production of SLPI in immortalized human oral
      keratinocytes. Brief exposure of cells to HIV-1 BaL and HXB2 significantly
      increased SLPI mRNA and protein production compared to that in mock-exposed cells
      (P < 0.01), as evaluated by real-time quantitative reverse transcription-PCR and
      enzyme-linked immunosorbent assay. HIV-1-mediated stimulation of SLPI occurred at
      the transcriptional level, was dose and time dependent, was elicited by heat
      inactivated and infectious viruses, and did not depend on cellular infection.
      Experiments with purified retroviral proteins showed that the stimulatory effect
      was induced specifically by external envelope glycoproteins from HIV-1 and simian
      immunodeficiency virus. SLPI responsiveness to HIV-1 was also observed in an
      unrelated oral epithelial cell line and in normal (nonimmortalized) human oral
      epithelial cells isolated from healthy uninfected gingival tissues. In this first
      report of SLPI regulation by HIV-1, we show that the expression and production of
      the antimicrobial and anti-inflammatory protein can be stimulated in oral
      epithelial cells by the virus through interactions with gp120 in the absence of
      direct infection. These findings indicate that SLPI is a component of the oral
      mucosal response to HIV-1.

PMID- 15858027
TI  - Interleukin-1 is responsible for acute lung immunopathology but increases
      survival of respiratory influenza virus infection.
AB  - Interleukin-1alpha (IL-1alpha) and IL-1beta are proinflammatory cytokines, which
      induce a plethora of genes and activities by binding to the type 1 IL-1 receptor
      (IL-1R1). We have investigated the role of IL-1 during pulmonary antiviral immune
      responses in IL-1R1(-/-) mice infected with influenza virus. IL-1R1(-/-) mice
      showed markedly reduced inflammatory pathology in the lung, primarily due to
      impaired neutrophil recruitment. Activation of CD4(+) T cells in secondary
      lymphoid organs and subsequent migration to the lung were impaired in the absence
      of IL-1R1. In contrast, activation of virus-specific cytotoxic T lymphocytes and
      killing of virus-infected cells in the lung were intact. Influenza virus-specific
      immunoglobulin G (IgG) and IgA antibody responses were intact, while the IgM
      response was markedly reduced in both serum and mucosal sites in IL-1R1(-/-)
      mice. We found significantly increased mortality in the absence of IL-1R1;
      however, lung viral titers were only moderately increased. Our results
      demonstrate that IL-1alpha/beta mediate acute pulmonary inflammatory pathology
      while enhancing survival during influenza virus infection. IL-1alpha/beta appear
      not to influence killing of virus-infected cells but to enhance IgM antibody
      responses and recruitment of CD4(+) T cells to the site of infection.

PMID- 15858028
TI  - Acylation-mediated membrane anchoring of avian influenza virus hemagglutinin is
      essential for fusion pore formation and virus infectivity.
AB  - Attachment of palmitic acid to cysteine residues is a common modification of
      viral glycoproteins. The influenza virus hemagglutinin (HA) has three conserved
      cysteine residues at its C terminus serving as acylation sites. To analyze the
      structural and functional roles of acylation, we have generated by reverse
      genetics a series of mutants (Ac1, Ac2, and Ac3) of fowl plague virus (FPV)
      containing HA in which the acylation sites at positions 551, 559, and 562,
      respectively, have been abolished. When virus growth in CV1 and MDCK cells was
      analyzed, similar amounts of virus particles were observed with the mutants and
      the wild type. Protein patterns and lipid compositions, characterized by high
      cholesterol and glycolipid contents, were also indistinguishable. However,
      compared to wild-type virus, Ac2 and Ac3 virions were 10 and almost 1,000 times
      less infectious, respectively. Fluorescence transfer experiments revealed that
      loss of acyl chains impeded formation of fusion pores, whereas hemifusion was not
      affected. When the affinity to detergent-insoluble glycolipid (DIG) domains was
      analyzed by Triton X-100 treatment of infected cells and virions, solubilization
      of Ac2 and Ac3 HAs was markedly facilitated. These observations show that
      acylation of the cytoplasmic tail, while not necessary for targeting to DIG
      domains, promotes the firm anchoring and retention of FPV HA in these domains.
      They also indicate that tight DIG association of FPV HA is essential for
      formation of fusion pores and thus probably for infectivity.

PMID- 15858029
TI  - Functional chimeras of human immunodeficiency virus type 1 Gp120 and influenza A
      virus (H3) hemagglutinin.
AB  - In an attempt to produce a protein that will allow determination of the native
      human immunodeficiency virus type 1 (HIV-1) gp120 (Env) structure in its trimeric
      state, we fused the globular head of gp120 to the stalk region of influenza virus
      A (X31) hemagglutinin (HA). The chimeric protein (EnvHA) has been expressed by
      using a recombinant vaccinia virus system, and its functional characteristics
      were determined. EnvHA is expressed as a 120- to 150-kDa protein that can
      oligomerize to form dimers and trimers. It retains the low-pH (5.2 to 5.4)
      requirement of X31-HA to trigger membrane fusion but, unlike X31-HA, it is not
      absolutely dependent on exogenously added trypsin for protein processing to
      release the HA2 fusion peptide. In terms of receptor binding the chimeric protein
      retains specificity for human CD4 but, in relation to the membrane fusion event,
      it appears to lose the Env coreceptor specificity of the parental HIV-1 strains:
      NL43 for CXCR4 and JRFL for CCR5. These properties suggest that stable,
      functional EnvHAs are being produced and that they may be exploited in terms of
      structural studies. Further, the potential of introducing the envHA genes into
      influenza viruses, by use of reverse genetics, and their use as a therapeutic
      vaccine for HIV are discussed.

PMID- 15858030
TI  - Accumulation of amino acid substitutions promotes irreversible structural changes
      in the hemagglutinin of human influenza AH3 virus during evolution.
AB  - In order to clarify the effect of an accumulation of amino acid substitutions on
      the hemadsorption character of the influenza AH3 virus hemagglutinin (HA)
      protein, we introduced single-point amino acid changes into the HA1 domain of the
      HA proteins of influenza viruses isolated in 1968 (A/Aichi/2/68) and 1997
      (A/Sydney/5/97) by using PCR-based random mutation or site-directed mutagenesis.
      These substitutions were classified as positive or negative according to their
      effects on the hemadsorption activity. The rate of positive substitutions was
      about 50% for both strains. Of 44 amino acid changes that were identical in the
      two strains with regard to both the substituted amino acids and their positions
      in the HA1 domain, 22% of the changes that were positive in A/Aichi/2/68 were
      negative in A/Sydney/5/97 and 27% of the changes that were negative in
      A/Aichi/2/68 were positive in A/Sydney/5/97. A similar discordance rate was also
      seen for the antigenic sites. These results suggest that the accumulation of
      amino acid substitutions in the HA protein during evolution promoted irreversible
      structural changes and therefore that antigenic changes in the H3HA protein may
      not be limited.

PMID- 15858031
TI  - Evolution and distribution of class II-related endogenous retroviruses.
AB  - Endogenous retroviruses (ERVs) are widespread in vertebrate genomes and have been
      loosely grouped into "classes" on the basis of their phylogenetic relatedness to
      the established genera of exogenous retroviruses. Four of these genera-the
      lentiviruses, alpharetroviruses, betaretroviruses, and deltaretroviruses-form a
      well-supported clade in retroviral phylogenies, and ERVs that group with these
      genera have been termed class II ERVs. We used PCR amplification and sequencing
      of retroviral fragments from more than 130 vertebrate taxa to investigate the
      evolution of the class II retroviruses in detail. We confirm that class II
      retroviruses are largely confined to mammalian and avian hosts and provide
      evidence for a major novel group of avian retroviruses, and we identify
      additional members of both the alpha- and the betaretrovirus genera. Phylogenetic
      analyses demonstrated that the avian and mammalian viruses form distinct
      monophyletic groups, implying that interclass transmission has occurred only
      rarely during the evolution of the class II retroviruses. In contrast to previous
      reports, the lentiviruses clustered as sister taxa to several endogenous
      retroviruses derived from rodents and insectivores. This topology was further
      supported by the shared loss of both the class II PR-Pol frameshift site and the
      class II retrovirus G-patch domain.

PMID- 15858033
TI  - Human circovirus TT virus genotype 6 expresses six proteins following
      transfection of a full-length clone.
AB  - The expression profile of the circovirus TTV has not yet been fully
      characterized. In this paper, we show that following transfection of a full
      length viral clone of TTV genotype 6, each of the three virally encoded mRNAs is
      translated from two initiating AUGs, and therefore, the TTV genome generates at
      least six proteins. Localization studies of hemagglutinin-tagged versions of
      these proteins in fixed cells, and green fluorescent protein-tagged versions of
      these proteins in living cells, expressed following transfection, demonstrated
      that two were primarily nuclear, two were primarily cytoplasmic, and two were
      found throughout the cell.

PMID- 15858032
TI  - Comparative genomics of foot-and-mouth disease virus.
AB  - Here we present complete genome sequences, including a comparative analysis, of
      103 isolates of foot-and-mouth disease virus (FMDV) representing all seven
      serotypes and including the first complete sequences of the SAT1 and SAT3
      genomes. The data reveal novel highly conserved genomic regions, indicating
      functional constraints for variability as well as novel viral genomic motifs with
      likely biological relevance. Previously undescribed invariant motifs were
      identified in the 5' and 3' untranslated regions (UTR), as was tolerance for
      insertions/deletions in the 5' UTR. Fifty-eight percent of the amino acids
      encoded by FMDV isolates are invariant, suggesting that these residues are
      critical for virus biology. Novel, conserved sequence motifs with likely
      functional significance were identified within proteins L(pro), 1B, 1D, and 3C.
      An analysis of the complete FMDV genomes indicated phylogenetic incongruities
      between different genomic regions which were suggestive of interserotypic
      recombination. Additionally, a novel SAT virus lineage containing nonstructural
      protein-encoding regions distinct from other SAT and Euroasiatic lineages was
      identified. Insights into viral RNA sequence conservation and variability and
      genetic diversity in nature will likely impact our understanding of FMDV
      infections, host range, and transmission.

PMID- 15858034
TI  - Differences in the postfusion conformations of full-length and truncated class II
      fusion protein E of tick-borne encephalitis virus.
AB  - The trimeric postfusion structure of the C-terminally truncated fusion protein E
      of the flavivirus tick-borne encephalitis virus, a class II viral fusion protein,
      was previously determined (S. Bressanelli, K. Stiasny, S. L. Allison, E. A.
      Stura, S. Duquerroy, J. Lescar, F. X. Heinz, and F. A. Rey, EMBO J. 23:728-738,
      2004). In this study we compared the properties of this truncated form with the
      full-length trimer and found that the so-called stem-anchor region not only
      confers additional stability to the full-length molecule but also structurally
      modifies the protein domain carrying the fusion peptide loop. These data provide
      experimental evidence to support the model of a fusion process that leads to the
      interaction of the stem-anchor region with the fusion peptide loop in the
      postfusion trimer.

PMID- 15858035
TI  - Replication-defective adenovirus serotype 5 vectors elicit durable cellular and
      humoral immune responses in nonhuman primates.
AB  - The magnitude and durability of immune responses induced by replication-defective
      adenovirus serotype 5 (ADV5) vector-based vaccines were evaluated in the simian
      human immunodeficiency virus/rhesus monkey model. A single inoculation of
      recombinant ADV5 vector constructs induced cellular and humoral immunity, but the
      rapid generation of neutralizing anti-Ad5 antibodies limited the immunity induced
      by repeated vector administration. The magnitude and durability of the immune
      responses elicited by these vaccines were greater when they were delivered as
      boosting immunogens in plasmid DNA-primed monkeys than when they were used as
      single-modality immunogens. Therefore, administration of ADV5-based vectors in
      DNA-primed subjects may be a preferred use of this vaccine modality for
      generating long-term immune protection.

PMID- 15858036
TI  - Characterization of human immunodeficiency virus type 1 (HIV-1) envelope
      variation and neutralizing antibody responses during transmission of HIV-1
      subtype B.
AB  - We analyzed neutralization sensitivity and genetic variation of transmitted
      subtype B human immunodeficiency virus type 1 (HIV-1) in eight recently infected
      men who have sex with men and the virus from the six subjects who infected them.
      In contrast to reports of heterosexual transmission of subtype C HIV-1, in which
      the transmitted virus appears to be more neutralization sensitive, we demonstrate
      that in our study population, relatively few phenotypic changes in neutralization
      sensitivity or genotypic changes in envelope occurred during transmission of
      subtype B HIV-1. We suggest that limited genetic variation within the infecting
      host reduces the likelihood of selective transmission of neutralization-sensitive
      HIV.

PMID- 15858037
TI  - Selection for human immunodeficiency virus type 1 envelope glycosylation variants
      with shorter V1-V2 loop sequences occurs during transmission of certain genetic
      subtypes and may impact viral RNA levels.
AB  - Designing an effective human immunodeficiency virus type 1 (HIV-1) vaccine will
      rely on understanding which variants, from among the myriad of circulating HIV-1
      strains, are most commonly transmitted and determining whether such variants have
      an Achilles heel. Here we show that heterosexually acquired subtype A HIV-1
      envelopes have signature sequences that include shorter V1-V2 loop sequences and
      fewer predicted N-linked glycosylation sites relative to the overall population
      of circulating variants. In contrast, recently transmitted subtype B variants did
      not, and this was true for cases where the major risk factor was homosexual
      contact, as well as for cases where it was heterosexual contact. This suggests
      that selection during HIV-1 transmission may vary depending on the infecting
      subtype. There was evidence from 23 subtype A-infected women for whom there was
      longitudinal data that those who were infected with viruses with fewer potential
      N-linked glycosylation sites in V1-V2 had lower viral set point levels. Thus, our
      study also suggests that the extent of glycosylation in the infecting virus could
      impact disease progression.

PMID- 15858038
TI  - Structural elements of the tRNA TPsiC loop critical for nucleocytoplasmic
      transport are important for human immunodeficiency virus type 1 primer selection.
AB  - Human immunodeficiency virus type 1 (HIV-1) selects a host cell tRNA as the
      primer for the initiation of reverse transcription. In a previous study,
      transport of the intact tRNA from the nucleus to the cytoplasm during tRNA
      biogenesis was shown to be a requirement for the selection of the tRNA primer by
      HIV-1. To further examine the importance of tRNA structure for transport and the
      selection of the primer, yeast tRNA(Phe) mutants were designed such that the
      native tRNA structure would be disrupted to various extents. The capacity of the
      mutant tRNA(Phe) to complement a defective HIV-1 provirus that relies on the
      expression of yeast tRNA(Phe) for infectivity was determined. We found a direct
      relationship between intact tRNA conformation and the capacity to be selected by
      HIV-1 for use in reverse transcription. tRNA(Phe) mutants that retained the
      capacity for nucleocytoplasmic transport, indicative of overall intact
      conformation, complemented the defective provirus. The mutant tRNAs were not
      aminoacylated, and the levels of complementation were lower than that for wild
      type tRNA(Phe), which did undergo transport and aminoacylation. Taken together,
      these results demonstrate that HIV-1 primer selection is most dependent on a tRNA
      structure necessary for nucleocytoplasmic transport, consistent with primer
      selection occurring in the cytoplasm at or near the site of protein synthesis.

PMID- 15858039
TI  - Identification of a peach latent mosaic viroid hairpin able to act as a Dicer
      like substrate.
AB  - The ability of several viroids to induce posttranscriptional gene silencing has
      been demonstrated; however, the structure recognized by the Dicer enzyme(s)
      responsible for the initiation of this mechanism remains a mystery. Here, we show
      that the hairpin known to be implicated in the replication of peach latent mosaic
      viroid has the ability to trigger the Dicer enzyme(s). This domain, which is
      composed of a succession of several small stems separated by symmetrical bulges,
      is reminiscent of the precursor micro-RNAs.

PMID- 15858040
TI  - Functional characterization of the genomic promoter of borna disease virus (BDV):
      implications of 3'-terminal sequence heterogeneity for BDV persistence.
AB  - Borna disease virus (BDV) is an enveloped virus with a genome organization
      characteristic of Mononegavirales. However, based on its unique features, BDV is
      considered the prototypic member of a new virus family, Bornaviridae, within the
      order Mononegavirales. We have described the establishment of a reverse genetics
      system for the rescue of BDV RNA analogues, or minigenomes, that is based on the
      use of polymerase I/polymerase II. Using this BDV minigenome rescue system, we
      have examined the functional implications of the reported sequence heterogeneity
      found at the 5' and 3' termini of the BDV genome and also defined the minimal BDV
      genomic promoter within the 3'-terminal 25 nucleotides. Our results suggest that
      the accumulation of RNA genome species containing truncations of one to three
      nucleotides at their 3' termini may contribute to modulate BDV RNA replication
      and gene expression during long-term persistence.

PMID- 15858041
TI  - Low levels of human immunodeficiency virus type 1 DNA in high-risk seronegative
      men.
AB  - We detected human immunodeficiency virus type 1 (HIV-1) DNA at very low levels in
      sequential peripheral blood mononuclear cell samples of five out of six high
      risk, seronegative, homosexual men and five out of five individuals 7.8 to 1.6
      years prior to seroconversion. These data indicate a high prevalence of low-level
      HIV-1 DNA in exposed seronegative individuals.

PMID- 15858042
TI  - Role of genes that modulate host immune responses in the immunogenicity and
      pathogenicity of vaccinia virus.
AB  - Poxvirus vaccine vectors, although capable of eliciting potent immune responses,
      pose serious health risks in immunosuppressed individuals. We therefore
      constructed five novel recombinant vaccinia virus vectors which contained
      overlapping deletions of coding regions for the B5R, B8R, B12R, B13R, B14R, B16R,
      B18R, and B19R immunomodulatory gene products and assessed them for both
      immunogenicity and pathogenicity. All five of these novel vectors elicited both
      cellular and humoral immunity to the inserted HIV-BH10 env comparable to that
      induced by the parental Wyeth strain vaccinia virus. However, deletion of these
      immunomodulatory genes did not increase the immunogenicity of these vectors
      compared with the parental vaccinia virus. Furthermore, four of these vectors
      were slightly less virulent and one was slightly more virulent than the Wyeth
      strain virus in neonatal mice. Attenuated poxviruses have potential use as safer
      alternatives to current replication-competent vaccinia virus. Improved vaccinia
      virus vectors can be generated by deleting additional genes to achieve a more
      significant viral attenuation.

PMID- 15858043
TI  - Residues in the murine leukemia virus capsid that differentially govern
      resistance to mouse Fv1 and human Ref1 restrictions.
AB  - We identified new residues within a 101-amino-acid stretch of the murine leukemia
      virus capsid that differentially modulate resistance and susceptibility to the
      mouse Fv1 and human Ref1 genes. Among these residues, aspartate 92 and histidine
      117 are both required for Fv1(b) resistance, whereas the latter is sufficient to
      confer Ref1 resistance.

PMID- 15858044
TI  - Papillomavirus subtypes are natural and old taxa: phylogeny of human
      papillomavirus types 44 and 55 and 68a and -b.
AB  - A human papillomavirus (HPV) type is defined as an HPV isolate whose L1 gene
      sequence is at least 10% different from that of any other type, while a subtype
      is 2 to 10% different from any HPV type. In order to analyze the phylogeny behind
      the subtype definition, we compared 49 isolates of HPV type 44 (HPV-44) and its
      subtype HPV-55, previously misclassified as a separate type, and 41 isolates of
      the subtype pair HPV-68a and -b, sampled from cohorts in four continents. The
      subtypes of each pair are separated by deep dichotomic branching, and three of
      the four subtypes have evolved large phylogenetic clusters of genomic variants
      forming a "star" phylogeny, with some branches specific for ethnically defined
      cohorts. We conclude that subtypes of HPV types are natural and old taxa,
      equivalent to types, which either diverged more recently than types or evolved
      more slowly.

PMID- 15858045
TI  - Failure of the lamivudine-resistant rtM204I hepatitis B virus mutants to
      efficiently support hepatitis delta virus secretion.
AB  - Hepatitis delta virus (HDV) is encapsidated by the envelope proteins of hepatitis
      B virus (HBV). The major HBV lamivudine (LMV)-resistant mutations in the
      polymerase gene within the reverse transcriptase (rt) region at rtM204V or
      rtM204I are associated with changes in the overlapping envelope gene products, in
      particular, the gene encoding small envelope protein (s) at sI195M or
      sW196L/S/Stop. We have demonstrated that the LMV resistance mutations
      corresponding to sW196L/S inhibited secretion of HDV particles, while changes
      corresponding to sI195M did not affect secretion. Differential efficiencies of
      HBsAg proteins expressed by LMV-resistant HBV to support HDV secretion may have
      consequences for clinical prognosis as coinfected patients are treated with
      antiviral agents.

PMID- 15858046
TI  - Redundancy and synergy of neuronal ensembles in motor cortex.
AB  - We examined the ability of neuronal ensembles from rat motor cortex to predict
      behavioral performance during a reaction time task. We found that neurons that
      were the best individual predictors of task performance were not necessarily the
      neurons that contributed the most predictive information to an ensemble of
      neurons. To understand this result, we applied a framework for quantifying
      statistical relationships between neurons (Schneidman et al., 2003) to all
      possible combinations of neurons within our ensembles. We found that almost all
      neurons (96%) contributed redundant predictive information to the ensembles. This
      redundancy resulted in the maintenance of predictive information despite the
      removal of many neurons from each ensemble. Moreover, the balance of synergistic
      and redundant interactions depended on the number of neurons in the ensemble.
      Small ensembles could exhibit synergistic interactions (e.g., 23 +/- 9% of
      ensembles with two neurons were synergistic). In contrast, larger ensembles
      exhibited mostly redundant interactions (e.g., 99 +/- 0.1% of ensembles with
      eight neurons were redundant). We discuss these results with regard to
      constraints on interpreting neuronal ensemble data and with respect to motor
      cortex involvement in reaction time performance.

PMID- 15858047
TI  - Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which
      there are few therapeutics that affect the underlying disease mechanism. Recent
      epidemiological studies, however, suggest that lifestyle changes may slow the
      onset/progression of AD. Here we have used TgCRND8 mice to examine directly the
      interaction between exercise and the AD cascade. Five months of voluntary
      exercise resulted in a decrease in extracellular amyloid-beta (Abeta) plaques in
      the frontal cortex (38%; p = 0.018), the cortex at the level of the hippocampus
      (53%; p = 0.0003), and the hippocampus (40%; p = 0.06). This was associated with
      decreased cortical Abeta1-40 (35%; p = 0.005) and Abeta1-42 (22%; p = 0.04)
      (ELISA). The mechanism appears to be mediated by a change in the processing of
      the amyloid precursor protein (APP) after short-term exercise, because 1 month of
      activity decreased the proteolytic fragments of APP [for alpha-C-terminal
      fragment (alpha-CTF), 54% and p = 0.04; for beta-CTF, 35% and p = 0.03]. This
      effect was independent of mRNA/protein changes in neprilysin and insulin
      degrading enzyme and, instead, may involve neuronal metabolism changes that are
      known to affect APP processing and to be regulated by exercise. Long-term
      exercise also enhanced the rate of learning of TgCRND8 animals in the Morris
      water maze, with significant (p < 0.02) reductions in escape latencies over the
      first 3 (of 6) trial days. In support of existing epidemiological studies, this
      investigation demonstrates that exercise is a simple behavioral intervention
      sufficient to inhibit the normal progression of AD-like neuropathology in the
      TgCRND8 mouse model.

PMID- 15858048
TI  - Endogenous hydrogen peroxide regulates the excitability of midbrain dopamine
      neurons via ATP-sensitive potassium channels.
AB  - ATP-sensitive K+ (K(ATP)) channels link metabolic state to cell excitability.
      Here, we examined regulation of K(ATP) channels in substantia nigra dopamine
      neurons by hydrogen peroxide (H2O2), which is produced in all cells during
      aerobic metabolism. Blockade of K(ATP) channels by glibenclamide (100 nM) or
      depletion of intracellular H2O2 by including catalase, a peroxidase enzyme, in
      the patch pipette increased the spontaneous firing rate of all dopamine neurons
      tested in guinea pig midbrain slices. Using fluorescence imaging with
      dichlorofluorescein to visualize intracellular H2O2, we found that moderate
      increases in H2O2 during partial inhibition of glutathione (GSH) peroxidase by
      mercaptosuccinate (0.1-0.3 mM) had no effect on dopamine neuron firing rate.
      However, with greater GSH inhibition (1 mM mercaptosuccinate) or application of
      exogenous H2O2, 50% of recorded cells showed K(ATP) channel-dependent
      hyperpolarization. Responsive cells also hyperpolarized with diazoxide, a
      selective opener for K(ATP) channels containing sulfonylurea receptor SUR1
      subunits, but not with cromakalim, a selective opener for SUR2-based channels,
      indicating that SUR1-based K(ATP) channels conveyed enhanced sensitivity to
      elevated H2O2. In contrast, when endogenous H2O2 levels were increased after
      inhibition of catalase, the predominant peroxidase in the substantia nigra, with
      3-amino-1,2,4-triazole (1 mM), all dopamine neurons responded with glibenclamide
      reversible hyperpolarization. Fluorescence imaging of H2O2 indicated that
      catalase inhibition rapidly amplified intracellular H2O2, whereas inhibition of
      GSH peroxidase, a predominantly glial enzyme, caused a slower, smaller increase,
      especially in nonresponsive cells. Thus, endogenous H2O2 modulates neuronal
      activity via K(ATP) channel opening, thereby enhancing the reciprocal
      relationship between metabolism and excitability.

PMID- 15858049
TI  - Nerve growth factor rapidly increases muscarinic tone in mouse medial
      septum/diagonal band of Broca.
AB  - Nerve growth factor (NGF) has been implicated in maintaining and regulating
      normal functioning of the septohippocampal pathway. However, many aspects of its
      physiological actions and the underlying mechanisms await elucidation. In this
      study, we investigated the effect of acute NGF exposure on neurons in the mouse
      medial septum/diagonal band of Broca (MS/DB), focusing on the cholinergic neurons
      and the subpopulation of noncholinergic neurons that were identified to be
      putatively GABAergic. We report that MS/DB neurons in a thin slice preparation,
      when exposed to NGF via bath perfusion, rapidly and indiscriminately increased
      the rate of spontaneous firing in all MS/DB neurons. However, focal application
      of NGF to individual MS/DB neurons increased spontaneous firing in cholinergic,
      but not in the noncholinergic, subpopulation. The NGF-induced effect on
      cholinergic neurons was direct, requiring activation and signaling via TrkA
      receptors, which were immunohistochemically localized to the cholinergic neurons
      in the MS/DB. TrkA receptors were absent in putative GABAergic MS/DB neurons, and
      blockade of TrkA signaling in these and other noncholinergic neurons had no
      effect on their firing activity after exposure to NGF. Conversely, methyl
      scopolamine, blocked the increased firing activity of noncholinergic neurons
      during bath perfusion of NGF. We propose a cell type-specific mode of action for
      NGF in the MS/DB. The neurotrophin directly enhances cholinergic neuronal
      activity in the MS/DB through TrkA-mediated signaling, increasing acetylcholine
      release and, thus, muscarinic tone. This increase in muscarinic tone, in turn,
      results in heightened firing activity in noncholinergic MS/DB neurons.

PMID- 15858050
TI  - Glutamate receptors in perirhinal cortex mediate encoding, retrieval, and
      consolidation of object recognition memory.
AB  - Object recognition is consistently impaired in human amnesia and animal models
      thereof. Results from subjects with permanent brain damage have revealed the
      importance of the perirhinal cortex to object recognition memory. Here, we report
      evidence from rats for interdependent but distinct stages in object recognition
      memory (encoding, retrieval, and consolidation), which require glutamate receptor
      activity within perirhinal cortex. Transient blockade of AMPA receptor-mediated
      synaptic transmission within perirhinal cortex disrupted encoding for short- and
      long-term memory as well as retrieval and consolidation. In contrast, transient
      NMDA receptor blockade during encoding affected only long-term object recognition
      memory; NMDA receptor activity was also necessary for consolidation but not
      retrieval. These results further demonstrate the importance of perirhinal cortex
      for object recognition memory and suggest that, as in the hippocampus, AMPA and
      NMDA receptors mediate synaptic transmission and activity-dependent synaptic
      plasticity, respectively, in several stages of memory processing.

PMID- 15858051
TI  - Long-term depression at olfactory nerve synapses.
AB  - The synapses formed by the olfactory nerve (ON) convey sensory information to
      olfactory glomeruli, the first stage of central odor processing. Morphological
      and behavioral studies suggest that glomerular odor processing is plastic in
      neonate rodents. However, long-term synaptic plasticity, a cellular correlate of
      functional and structural plasticity, has not yet been demonstrated in this
      system. Here, we report that ON-->mitral cell (MC) synapses of 5- to 8-d-old mice
      express long-term depression (LTD) after brief low-frequency ON stimulation.
      Pharmacological techniques and imaging of presynaptic calcium signals demonstrate
      that ON-MC LTD is expressed presynaptically and requires the activation of
      metabotropic glutamate receptors but does not require fast synaptic transmission.
      LTD at the ON--> MC synapse is potentially relevant for the establishment,
      maintenance, and experience-dependent refinement of odor maps in the olfactory
      bulb.

PMID- 15858052
TI  - Mitochondrial calcium ion and membrane potential transients follow the pattern of
      epileptiform discharges in hippocampal slice cultures.
AB  - Emerging evidence suggests that mitochondrial dysfunction contributes to the
      pathophysiology of epilepsy. Recurrent mitochondrial Ca2+ ion load during
      seizures might act on mitochondrial membrane potential (DeltaPsim) and proton
      motive force. By using electrophysiology and confocal laser-scanning microscopy,
      we investigated the effects of epileptiform activity, as induced by low-Mg2+ ion
      perfusion in hippocampal slice cultures, on changes in DeltaPsim and in
      mitochondrial Ca2+ ion concentration ([Ca2+]m). The mitochondrial compartment was
      identified by monitoring DeltaPsim in the soma and dendrites of patched CA3
      pyramidal cells using the mitochondria-specific voltage-sensitive dye rhodamine
      123 (Rh-123). Interictal activity was accompanied by localized mitochondrial
      depolarization that was restricted to a few mitochondria in small dendrites. In
      contrast, robust Rh-123 release into the cytosol was observed during seizure-like
      events (SLEs), indicating simultaneous depolarization of mitochondria. This was
      critically dependent on Ca2+ ion uptake and extrusion, because inhibition of the
      mitochondrial Ca2+ ion uniporter by Ru360 and the mitochondrial Na+/Ca2+ ion
      exchanger by 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one
      but not the inhibitor of mitochondrial permeability transition pore, cyclosporin
      A, decreased the SLE-associated mitochondrial depolarization. The Ca2+ ion
      dependence of simultaneous mitochondrial depolarization suggested enhanced Ca2+
      ion cycling across mitochondrial membranes during epileptiform activity. Indeed,
      [Ca2+]m fluctuated during interictal activity in single dendrites, and these
      fluctuations spread over the entire mitochondrial compartment during SLEs, as
      revealed using mitochondria-specific dyes (rhod-2 and rhod-ff) and spatial
      frequency-based image analysis. These findings strengthen the hypothesis that
      epileptic activity results in Ca2+ ion-dependent changes in mitochondrial
      function that might contribute to the neuronal injury during epilepsy.

PMID- 15858053
TI  - Changes in brain activation during the acquisition of a multifrequency bimanual
      coordination task: from the cognitive stage to advanced levels of automaticity.
AB  - Little is known about activation changes reflecting overlearning, i.e., extensive
      motor training beyond asymptotic performance. Here we used functional magnetic
      resonance imaging to trace the neural shifts from an initial to a skilled
      (learning) and finally overlearned stage (automatization). Scanning occurred
      before training (PRE) and after 1 (MID) and 2 weeks (POST) of intensive practice
      on a new bimanual coordination task (>10,500 cycles). Kinematics revealed major
      improvements between PRE and MID sessions, whereas MID to POST session
      performance leveled off, indicative of learning and automatization, respectively.
      Imaging findings showed that activation decreased in bilateral opercular areas,
      bilateral ventrolateral prefrontal cortex, the right ventral premotor and
      supramarginal gyrus, and the anterior cingulate sulcus during the learning stage
      and in the supplementary motor area during the automatization stage. These
      changes are hypothesized to reflect decreases in attention-demanding sensory
      processing, as well as suppression of preferred coordination tendencies as a
      prelude to acquiring new coordination modes. Conversely, learning-related
      increases were observed in the primary motor cortex (M1), posterior cingulate
      zone (PCZ), putamen, and right anterior cerebellum. Importantly, both M1 and PCZ
      activation decreased again to initial level (PRE) during automated performance
      (POST). Only the putamen and anterior cerebellum remained more activated across
      both learning and automatization stages, supporting their crucial role in long
      term motor memory formation for coordination tasks.

PMID- 15858054
TI  - Nuclear Ca2+ and the cAMP response element-binding protein family mediate a late
      phase of activity-dependent neuroprotection.
AB  - The mechanism by which physiological synaptic NMDA receptor activity promotes
      neuronal survival is not well understood. Here, we show that that an episode of
      synaptic activity can promote neuroprotection for a long time after that activity
      has ceased. This long-lasting or "late phase" of neuroprotection is dependent on
      nuclear calcium signaling and cAMP response element (CRE)-mediated gene
      expression. In contrast, neuroprotection evoked acutely by ongoing synaptic
      activity relies solely on the activation of the phosphatidylinositol 3-kinase/Akt
      pathway. This "acute phase" does not require nuclear calcium signaling and is
      independent of activation of the CRE-binding protein (CREB) family of
      transcription factors. Thus, activity-dependent neuroprotection comprises two
      mechanistically distinct phases that differ in their spatial requirements for
      calcium and in their reliance on the CREB family.

PMID- 15858055
TI  - Behavioral stress enhances hippocampal CA1 long-term depression through the
      blockade of the glutamate uptake.
AB  - Behavioral stress has been shown to enhance long-term depression (LTD) in the CA1
      region of the hippocampus, but the underlying mechanisms remain unclear. In the
      present study, we found that selectively blocking NR2B-containing NMDA receptors
      (NMDARs) abolishes the induction of LTD by prolonged low-frequency stimulation
      (LFS) in slices from stressed animals. Additionally, there is no need to activate
      NR2A-containing or synaptic NMDARs to induce this LTD, suggesting that LTD
      observed in slices from stressed animals is triggered primarily by extrasynaptic
      NMDAR activation. In contrast, stress has no effect on LTD induced by either a
      brief bath application of NMDA or a combination of LFS with the glutamate-uptake
      inhibitor DL-threo-beta-benzyloxyaspartate (DL-TBOA). Furthermore, saturation of
      LFS-induced LTD in slices from stressed animals occludes the subsequent induction
      of LTD by LFS in the presence of dl-TBOA. We also found that stress induces a
      profound decrease in the glutamate uptake in the synaptosomal fraction of the
      hippocampal CA1 region. These effects were prevented when the animals were given
      a glucocorticoid receptor antagonist, 11beta,17beta-11[4-(dimethylamino)phenyl]
      17-hydroxy-17-(1-(propynyl)-estra-4,9-dien-3-one, before experiencing stress.
      These results suggest that the blockade of glutamate uptake is a potential
      mechanism underlying the stress-induced enhancement of LTD and point to a novel
      role for glutamate-uptake machinery in the regulation of synaptic plasticity
      induction.

PMID- 15858056
TI  - Using functional magnetic resonance imaging to assess adaptation and size
      invariance of shape processing by humans and monkeys.
AB  - Functional magnetic resonance imaging in awake monkeys and humans was used to
      compare object adaptation in shape-sensitive regions of these two species under
      identical and different size conditions. Object adaptation was similar in humans
      and monkeys under both conditions. Neither species showed complete size
      invariance, in agreement with single-cell studies. Both the macaque
      inferotemporal (IT) complex and human lateral occipital complex (LOC) displayed
      an anteroposterior gradient in object adaptation and size invariance, with the
      more anterior regions being more adaptable and size invariant. The results
      provide additional evidence for the homology between the macaque IT cortex and
      human LOC but also add to the growing list of differences between human and
      monkey intraparietal sulcus regions.

PMID- 15858057
TI  - Emergence of the pre-Botzinger respiratory rhythm generator in the mouse embryo.
AB  - To obtain insights into the emergence of rhythmogenic circuits supporting
      respiration, we monitored spontaneous activities in isolated brainstem and
      medullary transverse slice preparations of mouse embryos, combining
      electrophysiological and calcium imaging techniques. At embryonic day 15 (E15),
      in a restricted region ventral to the nucleus ambiguus, we observed the onset of
      a sustained high-frequency (HF) respiratory-like activity in addition to a
      preexisting low-frequency activity having a distinct initiation site, spatial
      extension, and susceptibility to gap junction blockers. At the time of its onset,
      the HF generator starts to express the neurokinin 1 receptor, is connected
      bilaterally, requires active AMPA/kainate glutamatergic synapses, and is
      modulated by substance P and the mu-opioid agonist D-Ala2-N-Me-Phe4-Glycol5
      enkephalin. We conclude that a rhythm generator sharing the properties of the
      neonatal pre-Botzinger complex becomes active during E15 in mice.

PMID- 15858058
TI  - Activation of protease-activated receptor-1 triggers astrogliosis after brain
      injury.
AB  - We have studied the involvement of the thrombin receptor [protease-activated
      receptor-1 (PAR-1)] in astrogliosis, because extravasation of PAR-1 activators,
      such as thrombin, into brain parenchyma can occur after blood-brain barrier
      breakdown in a number of CNS disorders. PAR1-/- animals show a reduced astrocytic
      response to cortical stab wound, suggesting that PAR-1 activation plays a key
      role in astrogliosis associated with glial scar formation after brain injury.
      This interpretation is supported by the finding that the selective activation of
      PAR-1 in vivo induces astrogliosis. The mechanisms by which PAR-1 stimulates
      glial proliferation appear to be related to the ability of PAR-1 receptor
      signaling to induce sustained extracellular receptor kinase (ERK) activation. In
      contrast to the transient activation of ERK by cytokines and growth factors, PAR
      1 stimulation induces a sustained ERK activation through its coupling to multiple
      G-protein-linked signaling pathways, including Rho kinase. This sustained ERK
      activation appears to regulate astrocytic cyclin D1 levels and astrocyte
      proliferation in vitro and in vivo. We propose that this PAR-1-mediated mechanism
      underlying astrocyte proliferation will operate whenever there is sufficient
      injury-induced blood-brain barrier breakdown to allow extravasation of PAR-1
      activators.

PMID- 15858059
TI  - Extracellular domains of alpha-neurexins participate in regulating synaptic
      transmission by selectively affecting N- and P/Q-type Ca2+ channels.
AB  - Neurexins constitute a large family of highly variable cell-surface molecules
      that may function in synaptic transmission and/or synapse formation. Each of the
      three known neurexin genes encodes two major neurexin variants, alpha- and beta
      neurexins, that are composed of distinct extracellular domains linked to
      identical intracellular sequences. Deletions of one, two, or all three alpha
      neurexins in mice recently demonstrated their essential role at synapses. In
      multiple alpha-neurexin knock-outs, neurotransmitter release from excitatory and
      inhibitory synapses was severely reduced, primarily probably because voltage
      dependent Ca2+ channels were impaired. It remained unclear, however, which
      neurexin variants actually influence exocytosis and Ca2+ channels, which domain
      of neurexins is required for this function, and which Ca2+-channel subtypes are
      regulated. Here, we show by electrophysiological recordings that transgenic
      neurexin 1alpha rescues the release and Ca2+-current phenotypes, whereas
      transgenic neurexin 1beta has no effect, indicating the importance of the
      extracellular sequences for the function of neurexins. Because neurexin 1alpha
      rescued the knock-out phenotype independent of the alpha-neurexin gene deleted,
      these data are consistent with a redundant function among different alpha
      neurexins. In both knock-out and transgenically rescued mice, alpha-neurexins
      selectively affected the component of neurotransmitter release that depended on
      activation of N- and P/Q-type Ca2+ channels, but left L-type Ca2+ channels
      unscathed. Our findings indicate that alpha-neurexins represent organizer
      molecules in neurotransmission that regulate N- and P/Q-type Ca2+ channels,
      constituting an essential role at synapses that critically involves the
      extracellular domains of neurexins.

PMID- 15858060
TI  - Function and coding in the blowfly H1 neuron during naturalistic optic flow.
AB  - Naturalistic stimuli, reconstructed from measured eye movements of flying
      blowflies, were replayed on a panoramic stimulus device. The directional movement
      sensitive H1 neuron was recorded from blowflies watching these stimuli. The
      response of the H1 neuron is dominated by the response to fast saccadic turns
      into one direction. The response between saccades is mostly inhibited by the
      front-to-back optic flow caused by the forward translation during flight. To
      unravel the functional significance of the H1 neuron, we replayed, in addition to
      the original behaviorally generated stimulus, two targeted stimulus
      modifications: (1) a stimulus in which flow resulting from translation was
      removed (this stimulus produced strong intersaccadic responses); and (2) a
      stimulus in which the saccades were removed by assuming that the head follows the
      smooth flight trajectory (this stimulus produced alternating zero or nearly
      saturating spike rates). The responses to the two modified stimuli are strongly
      different from the response to the original stimulus, showing the importance of
      translation and saccades for the H1 response to natural optic flow. The response
      to the original stimulus thus suggests a double function for the H1 neuron,
      assisting two major classes of movement-sensitive output neurons targeted by H1.
      First, its strong response to saccades may function as a saccadic suppressor (via
      one of its target neurons) for cells involved in figure-ground discrimination.
      Second, its intersaccadic response may increase the signal-to-noise ratio (SNR)
      of wide-field neurons involved in detecting translational optic flow between
      saccades, in particular when flying speeds are low or when object distances are
      large.

PMID- 15858061
TI  - Aldolases a and C are ribonucleolytic components of a neuronal complex that
      regulates the stability of the light-neurofilament mRNA.
AB  - A 68 nucleotide segment of the light neurofilament (NF-L) mRNA, spanning the
      translation termination signal, participates in regulating the stability of the
      transcript in vivo. Aldolases A and C, but not B, interact specifically with this
      segment of the transcript in vitro. Aldolases A and C are glycolytic enzymes
      expressed in neural cells, and their mRNA binding activity represents a novel
      function of these isozymes. This unsuspected new activity was first uncovered by
      Northwestern blotting of a brainstem/spinal cord cDNA library. It was confirmed
      by two-dimensional fractionation of mouse brain cytosol followed by Northwestern
      hybridization and protein sequencing. Both neuronal aldolases interact
      specifically with the NF-L but not the heavy neurofilament mRNA, and their
      binding to the transcript excludes the poly(A)-binding protein (PABP) from the
      complex. Constitutive ectopic expression of aldolases A and C accelerates the
      decay of a neurofilament transgene (NF-L) driven by a tetracycline inducible
      system. In contrast, mutant transgenes lacking mRNA sequence for aldolase binding
      are stabilized. Our findings strongly suggest that aldolases A and C are
      regulatory components of a light neurofilament mRNA complex that modulates the
      stability of NF-L mRNA. This modulation likely involves endonucleolytic cleavage
      and a competing interaction with the PABP. Interactions of aldolases A and C in
      NF-L expression may be linked to regulatory pathways that maintain the highly
      asymmetrical form and function of large neurons.

PMID- 15858062
TI  - Cholinergic basal forebrain neurons burst with theta during waking and
      paradoxical sleep.
AB  - It is known that acetylcholine can stimulate activation and promote plasticity in
      the cerebral cortex, yet it is not known how the cholinergic basal forebrain
      neurons, which release acetylcholine in the cortex, discharge in relation to
      natural cortical activity and sleep-wake states. By recording basal forebrain
      units in association with electroencephalographic activity across the sleep-wake
      cycle and labeling individual neurons with Neurobiotin for immunohistochemical
      identification, we show for the first time that cholinergic neurons discharge in
      bursts at maximal rates during active waking and paradoxical sleep, when gamma
      and theta electroencephalographic activity are maximal. They virtually cease
      firing during slow-wave sleep. Notably, their bursting discharge is synchronized
      with theta oscillations. Through their maximal firing and rhythmic theta
      discharge during active waking and paradoxical sleep, the cholinergic neurons can
      thus modulate the cortex to promote activation along with plasticity during these
      two states.

PMID- 15858063
TI  - Noradrenergic stimulation enhances human action monitoring.
AB  - Noradrenergic neurotransmission has been associated with the modulation of higher
      cognitive functions mediated by the prefrontal cortex. In the present study, the
      impact of noradrenergic stimulation on the human action-monitoring system, as
      indexed by event-related brain potentials, was examined. After the administration
      of a placebo or the selective alpha2-adrenoceptor antagonist yohimbine, which
      stimulates firing in the locus ceruleus and noradrenaline release,
      electroencephalograpic recordings were obtained from healthy volunteers
      performing a letter flanker task. Yohimbine led to an increase in the amplitude
      of the error-related negativity in conjunction with a significant reduction of
      action errors. Reaction times were unchanged, and the drug did not modify the N2
      in congruent versus incongruent trials, a measure of preresponse conflict, or
      posterror adjustments as measured by posterror slowing of reaction time. The
      present findings suggest that the locus ceruleus-noradrenaline system exerts a
      rather specific effect on human action monitoring.

PMID- 15858064
TI  - Identification of glyoxalase-I as a protein marker in a mouse model of extremes
      in trait anxiety.
AB  - For >15 generations, CD1 mice have been selectively and bidirectionally bred for
      either high-anxiety-related behavior (HAB-M) or low-anxiety-related behavior (LAB
      M) on the elevated plus-maze. Independent of gender, HAB-M were more anxious than
      LAB-M animals in a variety of additional tests, including those reflecting risk
      assessment behaviors and ultrasound vocalization, with unselected CD1 "normal"
      control (NAB-M) and cross-mated (CM-M) mice displaying intermediate behavioral
      scores in most cases. Furthermore, in both the forced-swim and tail-suspension
      tests, LAB-M animals showed lower scores of immobility than did HAB-M and NAB-M
      animals, indicative of a reduced depression-like behavior. Using proteomic and
      microarray analyses, glyoxalase-I was identified as a protein marker, which is
      consistently expressed to a higher extent in LAB-M than in HAB-M mice in several
      brain areas. The same phenotype-dependent difference was found in red blood cells
      with NAB-M and CM-M animals showing intermediate expression profiles of
      glyoxalase-I. Additional studies will examine whether glyoxalase-I has an impact
      beyond that of a biomarker to predict the genetic predisposition to anxiety- and
      depression-like behavior.

PMID- 15858065
TI  - Protein-protein coupling/uncoupling enables dopamine D2 receptor regulation of
      AMPA receptor-mediated excitotoxicity.
AB  - here is considerable evidence that dopamine D2 receptors can modulate AMPA
      receptor-mediated neurotoxicity. However, the molecular mechanism underlying this
      process remains essentially unclear. Here we report that D2 receptors inhibit
      AMPA-mediated neurotoxicity through two pathways: the activation of
      phosphoinositide-3 kinase (PI-3K) and downregulation of AMPA receptor plasma
      membrane expression, both involving a series of protein-protein
      coupling/uncoupling events. Agonist stimulation of D2 receptors promotes the
      formation of the direct protein-protein interaction between the third
      intracellular loop of the D2 receptor and the ATPase N-ethylmaleimide-sensitive
      factor (NSF) while uncoupling the NSF interaction with the carboxyl tail (CT) of
      the glutamate receptor GluR2 subunit of AMPA receptors. Previous studies have
      shown that full-length NSF directly couples to the GluR2CT and facilitates AMPA
      receptor plasma membrane expression. Furthermore, the CT region of GluR2 subunit
      is also responsible for several other intracellular protein couplings, including
      p85 subunit of PI-3K. Therefore, the direct coupling of D2-NSF and concomitant
      decrease in the NSF-GluR2 interaction results in a decrease of AMPA receptor
      membrane expression and an increase in the interaction between GluR2 and the p85
      and subsequent activation of PI-3K. Disruption of the D2-NSF interaction
      abolished the ability of D2 receptor to attenuate AMPA-mediated neurotoxicity by
      blocking the D2 activation-induced changes in PI-3K activity and AMPA receptor
      plasma membrane expression. Furthermore, the D2-NSF-GluR2-p85 interactions are
      also responsible for the D2 inhibition of ischemia-induced cell death. These data
      may provide a new avenue to identify specific targets for therapeutics to
      modulate glutamate receptor-governed diseases, such as stroke.

PMID- 15858066
TI  - A novel positive allosteric modulator of the alpha7 neuronal nicotinic
      acetylcholine receptor: in vitro and in vivo characterization.
AB  - Several lines of evidence suggest a link between the alpha7 neuronal nicotinic
      acetylcholine receptor (nAChR) and brain disorders including schizophrenia,
      Alzheimer's disease, and traumatic brain injury. The present work describes a
      novel molecule, 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea
      (PNU-120596), which acts as a powerful positive allosteric modulator of the
      alpha7 nAChR. Discovered in a high-throughput screen, PNU-120596 increased
      agonist-evoked calcium flux mediated by an engineered variant of the human alpha7
      nAChR. Electrophysiology studies confirmed that PNU-120596 increased peak agonist
      evoked currents mediated by wild-type receptors and also demonstrated a
      pronounced prolongation of the evoked response in the continued presence of
      agonist. In contrast, PNU-120596 produced no detectable change in currents
      mediated by alpha4beta2, alpha3beta4, and alpha9alpha10 nAChRs. PNU-120596
      increased the channel mean open time of alpha7 nAChRs but had no effect on ion
      selectivity and relatively little, if any, effect on unitary conductance. When
      applied to acute hippocampal slices, PNU-120596 increased the frequency of ACh
      evoked GABAergic postsynaptic currents measured in pyramidal neurons; this effect
      was suppressed by TTX, suggesting that PNU-120596 modulated the function of
      alpha7 nAChRs located on the somatodendritic membrane of hippocampal
      interneurons. Accordingly, PNU-120596 greatly enhanced the ACh-evoked inward
      currents in these interneurons. Systemic administration of PNU-120596 to rats
      improved the auditory gating deficit caused by amphetamine, a model proposed to
      reflect a circuit level disturbance associated with schizophrenia. Together,
      these results suggest that PNU-120596 represents a new class of molecule that
      enhances alpha7 nAChR function and thus has the potential to treat psychiatric
      and neurological disorders.

PMID- 15858067
TI  - Involvement of a Rac activator,P-Rex1, in neurotrophin-derived signaling and
      neuronal migration.
AB  - Rho-family GTPases play key roles in regulating cytoskeletal reorganization,
      contributing to many aspects of nervous system development. Their activities are
      known to be regulated by guanine nucleotide exchange factors (GEFs), in response
      to various extracellular cues. P-Rex1, a GEF for Rac, has been mainly
      investigated in neutrophils, in which this molecule contributes to reactive
      oxygen species formation. However, its role in the nervous system is essentially
      unknown. Here we describe the expression profile and a physiological function of
      P-Rex1 in nervous system development. In situ hybridization revealed that P-Rex1
      is dynamically expressed in a variety of cells in the developing mouse brain,
      including some cortical and DRG neurons. In migrating neurons in the intermediate
      zone, P-Rex1 protein was found to localize in the leading process and adjacent
      cytoplasmic region. When transfected in pheochromocytoma PC12 cells, P-Rex1 can
      be activated by NGF, causing an increase in GTP-bound Rac1 and cell motility.
      Deletion analyses suggested roles for distinct domains of this molecule.
      Experiments using a P-Rex1 mutant lacking the Dbl-homology domain, a dominant
      negative-like form, and small interfering RNA showed that endogenous P-Rex1 was
      involved in cell migration of PC12 cells and primary cultured neurons from the
      embryonic day 14 cerebral cortices, induced by extracellular stimuli (NGF, BDNF,
      and epidermal growth factor). Furthermore, in utero electroporation of the mutant
      protein into the embryonic cerebral cortex perturbed radial neuronal migration.
      These findings suggest that P-Rex1, which is expressed in a variety of cell
      types, is activated by extracellular cues such as neurotrophins and contributes
      to neuronal migration in the developing nervous system.

PMID- 15858068
TI  - A novel RNA-binding protein in neuronal RNA granules: regulatory machinery for
      local translation.
AB  - Local translation in neuronal dendrites is an important basis for long-term
      synaptic plasticity, and RNA granules in the dendrites are involved in the local
      translation. Here, we identify RNG105 (RNA granule protein 105), a novel RNA
      binding protein, as a component of the RNA granules in dendrites of hippocampal
      neurons. The RNG105-localizing RNA granules contain mRNAs, the translational
      products of which play key roles in synaptic plasticity. RNG105 has an ability to
      repress translation both in vitro and in vivo, consistent with the finding that
      the RNA granule is translationally arrested in the basal conditions. Dissociation
      of RNG105 from the RNA granules is induced by BDNF, a growth factor responsible
      for synaptic plasticity. The RNG105 dissociation is coincident with the induction
      of local translation near the granules. These findings suggest that RNG105 is a
      translational repressor in the RNA granules and provide insight into the link
      between RNG105 dynamics and local translational regulation.

PMID- 15858069
TI  - Foxg1 confines Cajal-Retzius neuronogenesis and hippocampal morphogenesis to the
      dorsomedial pallium.
AB  - It has been suggested that cerebral cortex arealization relies on positional
      values imparted to early cortical neuroblasts by transcription factor genes
      expressed within the pallial field in graded ways. Foxg1, encoding for one of
      these factors, previously was reported to be necessary for basal ganglia
      morphogenesis, proper tuning of cortical neuronal differentiation rates, and the
      switching of cortical neuroblasts from early generation of primordial plexiform
      layer to late production of cortical plate. Being expressed along a
      rostral/lateral(high)- to-caudal/medial(low) gradient, Foxg1, moreover, could
      contribute to shaping the cortical areal profile as a repressor of caudomedial
      fates. We tested this prediction by a variety of approaches and found that it was
      correct. We found that overproduction of Cajal-Retzius neurons characterizing
      Foxg1-/- mutants does not arise specifically from blockage of laminar
      histogenetic progression of neocortical neuroblasts, as reported previously, but
      rather reflects lateral-to-medial repatterning of their cortical primordium. Even
      if lacking a neocortical plate, Foxg1-/- embryos give rise to structures, which,
      for molecular properties and birthdating profile, are highly reminiscent of
      hippocampal plate and dentate blade. Remarkably, in the absence of Foxg1,
      additional inactivation of the medial fates promoter Emx2, although not
      suppressing cortical specification, conversely rescues overproduction of
      Reelin(on) neurons.

PMID- 15858071
TI  - Designing deaf babies and the question of disability.
AB  - This article explores the recent controversy surrounding a Deaf lesbian couple's
      deliberate attempt at finding a Deaf donor to increase their chances of having a
      d/Deaf baby. Many have criticized the Deaf couple for harming their child; Deaf
      advocates have responded that the couple's decision reflects a natural cultural
      desire. This article seeks to explore how the medical model of disability
      implicitly used on both sides of the debate has obscured important points. Once
      this controversy takes into consideration the social construction of disability,
      the ethical defense of seeking a deaf child gains further support. This leads to
      the ironic claim that seeking a deaf child could actually mitigate the conditions
      of disability within the family.

PMID- 15858070
TI  - Microglia overexpressing the macrophage colony-stimulating factor receptor are
      neuroprotective in a microglial-hippocampal organotypic coculture system.
AB  - Microglia with increased expression of the macrophage colony-stimulating factor
      receptor (M-CSFR; c-fms) are found surrounding plaques in Alzheimer's disease
      (AD) and in mouse models for AD and after ischemic or traumatic brain injury.
      Increased expression of M-CSFR causes microglia to adopt an activated state that
      results in proliferation, release of cytokines, and enhanced phagocytosis. To
      determine whether M-CSFR-induced microglial activation affects neuronal survival,
      we assembled a coculture system consisting of BV-2 microglia transfected to
      overexpress the M-CSFR and hippocampal organotypic slices treated with NMDA.
      Twenty-four hours after assembly of the coculture, microglia overexpressing M
      CSFR proliferated at a higher rate than nontransfected control cells and
      exhibited enhanced migration toward NMDA-injured hippocampal cultures.
      Surprisingly, coculture with c-fms-transfected microglia resulted in a dramatic
      reduction in NMDA-induced neurotoxicity. Similar results were observed when
      cocultures were treated with the teratogen cyclophosphamide. Biolistic
      overexpression of M-CSFR on microglia endogenous to the organotypic culture also
      rescued neurons from excitotoxicity. Furthermore, c-fms-transfected microglia
      increased neuronal expression of macrophage colony-stimulating factor (M-CSF),
      the M-CSFR, and neurotrophin receptors in the NMDA-treated slices, as determined
      with laser capture microdissection. In the coculture system, direct contact
      between the exogenous microglia and the slice was necessary for neuroprotection.
      Finally, blocking expression of the M-CSF ligand by exogenous c-fms-transfected
      microglia with a hammerhead ribozyme compromised their neuroprotective
      properties. These results demonstrate a protective role for microglia
      overexpressing M-CSFR in our coculture system and suggest under certain
      circumstances, activated microglia can help rather than harm neurons subjected to
      excitotoxic and teratogen-induced injury.

PMID- 15858072
TI  - Comparing action gestures and classifier verbs of motion: evidence from
      Australian Sign Language, Taiwan Sign Language, and nonsigners' gestures without
      speech.
AB  - Recent research into signed languages indicates that signs may share some
      properties with gesture, especially in the use of space in classifier
      constructions. A prediction of this proposal is that there will be similarities
      in the representation of motion events by sign-naive gesturers and by native
      signers of unrelated signed languages. This prediction is tested for deaf native
      signers of Australian Sign Language (Auslan), deaf signers of Taiwan Sign
      Language (TSL), and hearing nonsigners using the Verbs of Motion Production task
      from the Test Battery for American Sign Language (ASL) Morphology and Syntax.
      Results indicate that differences between the responses of nonsigners, Auslan
      signers, and TSL signers and the expected ASL responses are greatest with
      handshape units; movement and location units appear to be very similar. Although
      not definitive, these data are consistent with the claim that classifier
      constructions are blends of linguistic and gestural elements.

PMID- 15858073
TI  - The efficacy of utilizing a phonics treatment package with middle school deaf and
      hard-of-hearing students.
AB  - Research indicates that the acquisition of phonemic awareness and phonic skills
      is highly correlated with later success in learning to read. Numerous studies
      support the hypothesis that deaf and hard-of-hearing children are able to utilize
      alternative systems to develop phonological awareness that are not dependent on
      the ability to hear sounds or accurately pronounce words. A quasi-experimental,
      pre- and posttest design was employed in this study that evaluated the efficacy
      of implementing a phonics treatment package with middle-school-aged students.
      Results indicate that treatment students were able to demonstrate acquisition and
      generalization of the phonic skills taught. Additionally, acquisition of these
      skills did not appear to be related to degree of hearing loss.

PMID- 15858074
TI  - Inflammation-dependent changes in alpha2,3-, alpha2,6-, and alpha2,8-sialic acid
      glycotopes on serum glycoproteins in mice.
AB  - The expression of acute-phase serum proteins increases in response to
      inflammatory stimuli. Most of these proteins are glycoproteins that often contain
      sialic acids (Sia). It is unknown, however, how the expression of Sia in these
      glycoproteins changes during inflammation. This study demonstrates changes in the
      alpha2,3-, alpha2,6-, and alpha2,8-Sia glycotopes on serum glycoproteins in
      response to turpentine oil-induced inflammation, based on lectin- and immunoblot
      analyses by using sialyl linkage-specific lectins, Maackia amurensis for the
      alpha2,3-Sia glycotope and Sambucus sieboldiana for the alpha2,6-Sia glycotopes,
      and monoclonal antibody 2-4B (mAb.2-4B) recognizing the di- and oligomers of the
      alpha2,8-Neu5Gc residue. There was an increase in a limited number of
      sialoglycoproteins containing the alpha2,3-, alpha2,6-, or alpha2,8-Sia
      glycotopes. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of
      the expression profiles of mRNAs for the known sialyltransferases in mouse liver
      during inflammation indicated the up-regulated expression of beta-galactoside
      alpha2,3-sialyltransferases (ST3Gal I and ST3Gal III) and beta-N
      acetylgalactosaminide alpha2,6-sialyltransferase (ST6GalNAc VI) as well as beta
      galactoside alpha2,6-sialyltransferase (ST6Gal I) mRNAs. Notably, ST3Gal I and
      III and ST6GalNAc VI are involved in the synthesis of the alpha2,3- and alpha2,6
      Sia glycotopes on O-glycan chains and possibly on gangliosides, whereas ST6Gal I
      is specific for N-glycan chains. These results provide evidence for the
      inflammation-induced expression of sialyl glycotopes in serum glycoproteins. We
      demonstrated that inflammation significantly increased the expression of an
      unknown 32-kDa glycoprotein containing the alpha2,8-Sia glycotope. The mechanism
      for the increase in glycoprotein in inflamed mouse serum remains to be examined,
      as mRNA expression for all of the alpha2,8-sialyltransferases (ST8Sia I-VI) was
      unchanged during inflammation.

PMID- 15858075
TI  - Increased sialylation and defucosylation of plasma proteins are early events in
      the acute phase response.
AB  - Within hours of turpentine injection to stimulate the acute phase (AP) response
      in rats, the N-acetylneuraminic acid content of plasma proteins increases and
      that of fucose decreases, each by about 60%. The two changes are inversely
      related (r = -0.97). The NeuAc/Gal ratio increases from the normal 0.75 to 1.0 on
      day 2 of the AP. Whereas 50% of the isolated oligosaccharides of normal plasma
      proteins are retarded on immobilized Ricinus communis agglutinin, those from day
      2 AP plasma fail to do so. This indicates that NeuAc caps the normally Gal
      terminated chains. alpha1-Acid glycoprotein (a positive AP protein), alpha1
      macroglobulin (a non-AP protein), and alpha1-inhibitor3 (a negative AP protein)
      also show similar alterations in NeuAc/Gal ratio and decreases in Fuc. alpha2
      Macroglobulin, which arises only during the AP, does not contain significant
      amounts of Fuc. Sambucus nigra agglutinin (alpha2,6-linked NeuAc-specific) binds
      a majority of plasma proteins, and binding is increased during the AP response.
      Maackia amurensis lectin (alpha2,3-linked NeuAc-specific) binds only three
      proteins in normal plasma and three additional proteins in AP plasma. The Fuc
      specific Aleuria aurantia agglutinin and Lens culinaris agglutinin each detect
      five proteins in normal plasma. Their binding decreases during the AP response.
      These results show that: (1) sialylation and defucosylation of preexisting plasma
      proteins occur rapidly in the AP response; (2) sialylation caps the preexisting
      Gal-terminating oligosaccharides; and (3) the oligosaccharides of even the non-AP
      and negative AP proteins are modified. These changes are distinct from the
      elevation in the levels of protein-bound monosaccharides and the altered
      concanavalin A-binding profile the oligosaccharides of AP proteins acquire in
      diseases.

PMID- 15858076
TI  - Discovery of novel flavin-containing monooxygenase 3 (FMO3) single nucleotide
      polymorphisms and functional analysis of upstream haplotype variants.
AB  - The flavin-containing monooxygenases (FMOs) are important for xenobiotic
      metabolism. FMO3, the predominant FMO enzyme in human adult liver, exhibits
      significant interindividual variation that is poorly understood. This study was
      designed to identify common FMO3 genetic variants and determine their potential
      for contributing to interindividual differences in FMO3 expression. FMO3 single
      nucleotide polymorphism (SNP) discovery was accomplished by resequencing DNA
      samples from the Coriell Polymorphism Discovery Resource. Population-specific SNP
      frequencies were determined by multiplexed, single-base extension using DNA from
      201 Hispanic American (Mexican descent), 201 African American, and 200 White
      (northern European descent) subjects. Haplotypes were inferred and population
      frequencies estimated using PHASE version 2.1. Multiple site-directed mutagenesis
      was used to introduce inferred upstream haplotypes into an FMO3/luciferase
      construct for functional analysis in HepG2 cells. Sequence analysis revealed
      seven FMO3 upstream SNPs, 11 exon SNPs, and 22 intron SNPs. Five of the latter
      fell within consensus splice sites. A g.72G>T variant (E24D) is predicted to
      impact the structure of the Rossmann fold involved in FAD binding, whereas a
      g.11177C>A variant (N61K) is predicted to disrupt the secondary structure of a
      conserved membrane interaction domain. Seven common (>1%) promoter region
      haplotypes were inferred in one or more of the study populations that differed in
      estimated frequency among the groups. Haplotype 2 resulted in an 8-fold increase
      in promoter activity, whereas haplotypes 8 and 15 exhibited a near complete loss
      of activity. In conclusion, FMO3 promoter haplotype variants modulate gene
      function and probably contribute to interindividual differences in FMO3
      expression.

PMID- 15858077
TI  - Science to Practice: High-intensity focused ultrasound ablation: will image
      guided therapy replace conventional surgery?

PMID- 15858078
TI  - Radiology education in the digital era.

PMID- 15858079
TI  - Cost-effectiveness analysis in the assessment of diagnostic imaging technologies.
AB  - In many ways, diagnostic technologies differ from therapeutic medical
      technologies. Perhaps most important, diagnostic technologies do not generally
      directly affect long-term patient outcomes. Instead, the results of diagnostic
      tests can influence the care of patients; in that way, diagnostic tests may
      affect long-term outcomes. Because of this, the benefits associated with the use
      of a specific diagnostic technology will depend on the performance
      characteristics (eg, sensitivity and specificity) of the test, as well as other
      factors, such as prevalence of disease and effectiveness of available treatments
      for the disease in question. The fact that diagnostic tests affect short-term, or
      "surrogate," outcomes, rather than long-term patient outcomes makes evaluation of
      these tests more complicated than the evaluation of therapeutic technologies.
      This article will trace the history of technology assessment in medicine, address
      the role of cost-effectiveness and decision analysis in health technology
      assessment, and describe unique features and approaches to assessing diagnostic
      technologies. The article will then conclude with a consideration of the limits
      of medical technology assessment.

PMID- 15858080
TI  - Clinical prediction rules in trauma imaging: who, how, and why?
AB  - Clinical prediction rules are multifactorial tools used to aid in clinical
      decision making. In radiology, clinical prediction rules are an important method
      for determining who should undergo imaging and, in combination with cost
      effectiveness analysis, how imaging should be performed. To be useful, clinical
      prediction rules should be clinically important, have face validity, be
      reproducible and easy to use, be clinically relevant, and suggest a course of
      action. To insure generalizability, clinical prediction rules should also be
      validated in subjects distinct from those used to develop the rule. In this
      review, several examples from trauma imaging are used to demonstrate the
      development, validation, and use of clinical prediction rules.

PMID- 15858081
TI  - Decision making in the face of uncertainty and resource constraints: examples
      from trauma imaging.
AB  - The purpose of this review is to illustrate how tools and concepts from decision
      and cost-effectiveness analyses can be used to help make decisions in the face of
      uncertainty and resource constraints, select appropriate subjects for imaging,
      choose between competing imaging modalities, and prioritize future research.
      Examples from trauma imaging illustrate the use of the presented tools. The
      author advocates the PROACTIVE approach in deciding which imaging strategies are
      cost-effective (PRO for defining the problem, reframing the problem from multiple
      perspectives, and focusing on the objective; ACT for expanding the alternatives,
      considering the consequences and associated chances of each alternative, and
      identifying the trade-offs involved; IVE for integrating the evidence and values,
      optimizing the value of interest, and exploring uncertainty). Simulation models
      play an important role in the assessment of imaging strategies by helping to
      identify alternative strategies and to integrate the best-available evidence
      related to risks, benefits, patient values, and costs. Exploring the uncertainty
      in the evidence and assessing the value of obtaining more information can help
      prioritize future research and guide study design.

PMID- 15858082
TI  - Measuring coronary calcium on CT images adjusted for attenuation differences.
AB  - PURPOSE: To quantify scanner and participant variability in attenuation values
      for computed tomographic (CT) images assessed for coronary calcium and define a
      method for standardizing attenuation values and calibrating calcium measurements.
      MATERIALS AND METHODS: Institutional review board approval and participant
      informed consent were obtained at all study sites. An image attenuation
      adjustment method involving the use of available calibration phantom data to
      define standard attenuation values was developed. The method was applied to
      images from two population-based multicenter studies: the Coronary Artery Risk
      Development in Young Adults study (3041 participants) and the Multi-Ethnic Study
      of Atherosclerosis (6814 participants). To quantify the variability in
      attenuation, analysis of variance techniques were used to compare the CT numbers
      of standardized torso phantom regions across study sites, and multivariate linear
      regression models of participant-specific calibration phantom attenuation values
      that included participant age, race, sex, body mass index (BMI), smoking status,
      and site as covariates were developed. To assess the effect of the calibration
      method on calcium measurements, Pearson correlation coefficients between
      unadjusted and attenuation-adjusted calcium measurements were computed.
      Multivariate models were used to examine the effect of sex, race, BMI, smoking
      status, unadjusted score, and site on Agatston score adjustments. RESULTS: Mean
      attenuation values (CT numbers) of a standard calibration phantom scanned beneath
      participants varied significantly according to scanner and participant BMI (P <
      .001 for both). Values were lowest for Siemens multi-detector row CT scanners
      (110.0 HU), followed by GE-Imatron electron-beam (116.0 HU) and GE LightSpeed
      multi-detector row scanners (121.5 HU). Values were also lower for morbidly obese
      (BMI, > or =40.0 kg/m(2)) participants (108.9 HU), followed by obese (BMI, 30.0
      39.9 kg/m(2)) (114.8 HU), overweight (BMI, 25.0-29.9 kg/m(2)) (118.5 HU), and
      normal-weight or underweight (BMI, <25.0 kg/m(2)) (120.1 HU) participants.
      Agatston score calibration adjustments ranged from -650 to 1071 (mean, -8 +/- 50
      [standard deviation]) and increased with Agatston score (P < .001). The direction
      and magnitude of adjustment varied significantly according to scanner and BMI (P
      < .001 for both) and were consistent with phantom attenuation results in that
      calibration resulted in score decreases for images with higher phantom
      attenuation values. CONCLUSION: Image attenuation values vary by scanner and
      participant body size, producing calcium score differences that are not due to
      true calcium burden disparities. Use of calibration phantoms to adjust
      attenuation values and calibrate calcium measurements in research studies and
      clinical practice may improve the comparability of such measurements between
      persons scanned with different scanners and within persons over time.

PMID- 15858083
TI  - Coronary artery stenoses: detection with calcium scoring, CT angiography, and
      both methods combined.
AB  - PURPOSE: To investigate prospectively the relative accuracy of computed
      tomographic (CT) angiography, calcium scoring (CS), and both methods combined in
      demonstrating coronary artery stenoses by using conventional angiography as the
      reference standard. MATERIALS AND METHODS: The study was approved by the
      institutional review board Human Research Ethics Committee, and all patients
      completed written informed consent. Fifty patients (40 men, 10 women) aged 62
      years +/- 11 (+/- standard deviation) who were suspected of having coronary
      artery disease underwent both conventional coronary angiography and multisection
      coronary CT angiography with CS. Sensitivity and specificity of CS, CT
      angiography, and both methods combined in demonstrating luminal stenosis greater
      than or equal to 50% were determined for each arterial segment, coronary vessel,
      and patient. Receiver operating characteristic (ROC) curves were generated for CS
      prediction of significant stenosis, and the Mann-Whitney U test was used for
      comparison of CS between groups. RESULTS: When used with segment-specific
      electrocardiographic phase reconstructions, CT angiography demonstrated stenosed
      segments with 79% sensitivity and 95% specificity. Mean calcium score was greater
      in segments, vessels, and patients with stenoses than in segments, vessels, and
      patients without stenoses (P < .001 for all); nine (16%) of 56 stenosed segments,
      however, had a calcium score of 0. The patient calcium score correlated strongly
      with the number of stenosed arteries (Spearman rho = 0.75, P < .001). CS was more
      accurate in demonstrating stenosis in patients than in segments (areas under ROC
      curve were 0.88 and 0.74, respectively). CT angiography, however, was more
      accurate than CS in demonstrating stenosis in patients, vessels, and segments.
      The sensitivity and specificity of CS varied according to the threshold used, but
      when the calcium score cutoff (ie, >150) matched the specificity of CT
      angiography (95%), the sensitivity of CS in demonstrating stenosed segments was
      29% (compared with 79% for CT angiography). Combining CT angiography with CS (at
      threshold of 400) improved the sensitivity of CT angiography (from 93% to 100%)
      in demonstrating significant coronary disease in patients, without a loss of
      specificity (85%); this finding, however, was not statistically significant.
      CONCLUSION: CT angiography is more accurate than CS in demonstrating coronary
      stenoses. A patient calcium score of greater than or equal to 400, however, can
      be used to potentially identify patients with significant coronary stenoses not
      detected at CT angiography.

PMID- 15858084
TI  - Coronary artery disease: myocardial perfusion MR imaging with sensitivity
      encoding versus conventional angiography.
AB  - PURPOSE: To evaluate the technical performance of sensitivity encoding (SENSE)
      accelerated myocardial perfusion magnetic resonance (MR) imaging and
      prospectively assess the diagnostic accuracy of this examination for depiction of
      significant coronary artery disease (CAD). MATERIALS AND METHODS: All 102
      subjects provided written informed consent, and the local ethics committee
      approved the study. A saturation-recovery segmented k-space gradient-echo pulse
      sequence was combined with SENSE to allow dynamic acquisition of myocardial
      perfusion data on four parallel short-axis MR image sections at every heartbeat.
      This technique was evaluated in 10 healthy volunteers and in 92 patients
      scheduled to undergo conventional coronary angiography. Gadopentetate dimeglumine
      was peripherally injected at rest and during adenosine-induced stress. The
      maximal upslope of the signal intensity-time profiles was plotted for 16
      myocardial segments defined on three MR image sections, and a myocardial
      perfusion reserve index (MPRI) between stress and rest, normalized to the input
      function from the blood pool of the most basal section, was calculated. Areas
      under receiver operating characteristic curves (AUCs) were used to assess the
      diagnostic performance of cardiac MR imaging for depiction of greater than 70%
      CAD seen at coronary angiography, the reference standard. RESULTS: In volunteers,
      the mean myocardial enhancement was 2.1 +/- 1.2 (standard deviation), with
      homogeneous signal intensity distribution across the segments. The diagnostic
      accuracy of MPRI measurements was high (AUC, 0.908; sensitivity, 88% [52 of 59
      patients]; specificity, 82% [27 of 33 patients]). Diagnostic performance was
      similar among separate analyses of the three coronary territories and among
      separate analyses of data in the patients with diabetes mellitus, left
      ventricular hypertrophy, or myocardial infarction. CONCLUSION: Multisection
      myocardial perfusion MR imaging with SENSE is feasible and has high diagnostic
      accuracy in the detection of CAD.

PMID- 15858086
TI  - Case 82: polyorchidism with torsion.

PMID- 15858087
TI  - Early signs of brain infarction at CT: observer reliability and outcome after
      thrombolytic treatment--systematic review.
AB  - PURPOSE: To review systematically all reported early computed tomographic (CT)
      signs in acute ischemic stroke to determine interobserver agreement and the
      relationship between early CT signs and patient outcome with or without
      thrombolysis. MATERIALS AND METHODS: A systematic review of the literature was
      conducted by using Cochrane Stroke Group methodology to identify studies
      published between 1990 and 2003 that were performed to assess interobserver
      agreement about early signs of infarction on CT scans obtained within 6 hours
      after onset of stroke symptoms and determine the relation of early signs of
      infarction to clinical outcome, including any interactive effect of thrombolysis.
      Interobserver agreement was measured with the kappa statistic, sensitivity, and
      specificity. The relation of early signs to clinical outcome with or without
      thrombolysis was assessed with calculated odds ratios and 95% confidence
      intervals. RESULTS: In 15 studies of interobserver agreement (median of 30 CT
      scans and six raters), the prevalence of all early infarction signs was 61% +/-
      21 (standard deviation). Interobserver agreement (kappa statistics) ranged from
      0.14 to 0.78 for any early infarction sign. The mean sensitivity and specificity
      for detection of early infarction signs with CT were 66% (range, 20%-87%) and 87%
      (range, 56%-100%), respectively. Experience improved detection, but knowledge of
      symptoms did not. In 15 studies of early infarction signs and outcome (including
      seven thrombolysis trials) in 3468 patients, any early infarction sign increased
      the risk of poor outcome (odds ratio, 3.11; 95% confidence interval: 2.77, 3.49).
      Two studies that sought interaction between early infarction signs and
      thrombolysis found no evidence that thrombolysis given in the presence of early
      infarction signs resulted in worse outcome than that due to early signs alone.
      CONCLUSION: Further work is required to determine which signs are most reliably
      detected, whether scoring systems help to improve detection, and whether any
      early infarction sign should influence decisions concerning thrombolysis.

PMID- 15858088
TI  - Vessel wall damage caused by cerebral protection devices: ex vivo evaluation in
      porcine carotid arteries.
AB  - PURPOSE: To determine the extent of vessel wall damage caused by cerebral
      protection devices designed for carotid angioplasty by using ex vivo porcine
      carotid arteries. MATERIALS AND METHODS: The local animal experimentation
      committee did not require its approval for this study. With a benchtop vascular
      model (flow rate, 470 mL/min; dicrotic pulsatile flow, 76 pulses per minute;
      pressure, 115/67 mm Hg [mean pressure, 91 mm Hg]) into which 85 porcine internal
      carotid arteries (ICAs) were inserted, five different protection devices
      (Angioguard [Cordis/Johnson & Johnson, Miami, Fla], Filterwire EX [Boston
      Scientific, Natick, Mass], Trap [Microvena, White Bear Lake, Minn], Neuroshield
      [Abbott Laboratories, Redwood City, Calif], and Percusurge [Abbott Laboratories])
      were evaluated. Adverse movement (1 cm up, 2 cm down, and 1 cm up again) of the
      activated devices (deployed filters or inflated balloons [Percusurge only]) was
      simulated, and the device was retrieved. For each of these steps (deployment,
      movement, retrieval) the amount of debris from the vessel wall in the effluent of
      the ICA was determined by using a 100-microm filter. The Mann-Whitney test was
      used to test for differences, and a correction for multiple comparisons was made.
      P < .05 was considered to indicate a significant difference. The authors
      attempted to determine whether there was a notable association between the total
      amount of debris captured and the classification of damage at microscopy. Carotid
      arteries were analyzed histologically with light and scanning electron
      microscopy. RESULTS: All examined protection devices caused dislodged debris,
      which was captured in the effluent filter. There were significant differences
      among the devices in terms of the total amount of debris captured in the filters
      (lowest amounts of debris, 4.75 mg [Angioguard] and 5.02 mg [Filterwire EX];
      highest amount, 7.51 mg [Trap]; P < or = .001 for all). All devices caused
      histologically visible wall damage, with the degree of intimal denudation
      correlating with the mass of the debris. The Trap device caused the most severe
      intimal and subintimal wall damage. Adverse movement resulted in no increased
      debris dislodgment as compared with the debris dislodged during deployment and
      retrieval of the devices. CONCLUSION: On the basis of the data obtained, cerebral
      protection devices themselves have a potential influence on embolization rates by
      causing debris to be dislodged during carotid stent placement.

PMID- 15858089
TI  - Combination radiofrequency ablation with intratumoral liposomal doxorubicin:
      effect on drug accumulation and coagulation in multiple tissues and tumor types
      in animals.
AB  - PURPOSE: To determine whether use of radiofrequency (RF) ablation combined with
      intravenously (IV) administered liposomal doxorubicin, as compared with use of RF
      ablation or doxorubicin alone, facilitates increased tissue coagulation and
      interstitial drug accumulation in animal models. MATERIALS AND METHODS: The
      institutional animal care and use committee approved this study. In experiment 1,
      multiple canine sarcomas were implanted in seven mildly immunosuppressed dogs and
      grown to a mean diameter of 4.8 cm. Tumors were assigned to three treatment
      groups: internally cooled RF ablation (12 minutes, 2000-mA pulsed technique)
      followed by IV liposomal doxorubicin (10 mg per animal) (n = 6), RF ablation
      alone (n = 6), and liposomal doxorubicin alone (n = 4). In experiment 2, the
      livers and kidneys of 10 rabbits and the thigh muscles of 10 rats were randomly
      assigned to one of two treatment groups: conventional RF ablation (90 degrees C
      +/- 2, 5 minutes) followed by IV liposomal doxorubicin (5 mg per rabbit, 1 mg per
      rat) or RF ablation alone (n = 5, each). Coagulation diameter and interstitial
      doxorubicin concentration (tissues were homogenized in acid alcohol, with
      doxorubicin extracted for 24 hours at 5 degrees C and quantified with
      fluorimetry) were measured 48 hours after treatment and compared. Multivariate
      analysis of variance and subsequent pairwise t tests (alpha = .05, two-tailed
      test) were performed. RESULTS: Data are means +/- standard errors of the mean. A
      larger diameter of tumor destruction was observed in canine sarcomas treated with
      RF ablation-liposomal doxorubicin (3.7 cm +/- 0.6) compared with that in tumors
      treated with RF ablation (2.3 cm +/- 0.1) or liposomal doxorubicin (0.0 cm +/-
      0.0) alone (P < .01). A new finding was a completely necrotic red zone (1.6 cm +/
      0.7) surrounding the central RF ablation-induced white coagulation zone. Greater
      but nonuniform drug uptake was observed particularly in this red zone (77.0 ng/g
      +/- 18.2) compared with uptake in the central zone (15.1 ng/g +/- 3.2),
      peripheral area of untreated tumor (38.9 ng/g +/- 8.0), and tumors treated with
      liposomal doxorubicin alone (43.9 ng/g +/- 6.7 for all regions) (P < .01 for all
      individual comparisons). In experiment 2, use of combined therapy led to
      increased coagulation in all tissues (liver: 17.6 mm +/- 3.1, P = .03; kidney:
      11.0 mm +/- 3.1, P = .03; muscle: 13.1 mm +/- 1.3, P < .01) compared with use of
      RF ablation alone (liver, 13.4 mm +/- 1.5; kidney, 7.9 mm +/- 0.7; muscle, 8.6 mm
      +/- 0.5). Combined therapy, as compared with liposomal doxorubicin therapy alone,
      was also associated with increased doxorubicin accumulation in liver, kidney, and
      muscle (1.56 microg/g +/- 0.34, 4.36 microg/g +/- 1.78, and 3.63 microg/g +/-
      1.43, respectively, vs 1.00 microg/g +/- 0.18, 1.23 microg/g +/- 0.32, and 0.87
      microg/g +/- 0.53, respectively) (P < or = .01 for all individual comparisons).
      CONCLUSION: Use of RF ablation combined with liposomal doxorubicin facilitates
      increased tissue coagulation and interstitial doxorubicin accumulation in
      multiple tissues and tumor types and may be useful for treatment of large tumors
      and achieving an ablative margin within the untreated tissue surrounding RF
      ablation-treated tumors.

PMID- 15858090
TI  - MR-guided percutaneous intramyocardial injection with an MR-compatible catheter:
      feasibility and changes in T1 values after injection of extracellular contrast
      medium in pigs.
AB  - PURPOSE: To assess the feasibility of percutaneous magnetic resonance (MR)-guided
      intramyocardial injection of gadodiamide by using real-time imaging and to
      quantify T1 values and the size of the enhanced region for different
      concentrations of contrast agent for 30 minutes after injection. MATERIALS AND
      METHODS: Animal care committee approval was obtained. A catheter with a needle
      tip was advanced into the left ventricle in seven pigs by using real-time imaging
      with radial steady-state free precession. After intramyocardial injection of 2 mL
      of solution at concentrations of 0.05 or 0.10 mmol/mL gadodiamide, local changes
      in T1 values and size of the contrast material-enhanced region were sequentially
      measured at 3, 15, and 30 minutes after injection by using the Look-Locker
      sequence. Two-tailed paired Student t tests were used for statistical analysis.
      RESULTS: Catheter guidance and visualization of contrast agent distribution were
      feasible in all animals. Regional changes in T1 values were significantly
      different for different contrast agent concentrations (for 0.05 mmol/mL, 456 msec
      +/- 5 [+/- standard error of the mean]; for 0.10 mmol/mL, 228 msec +/- 4; P <
      .001) measured 3 minutes after injection. T1 values increased significantly (P <
      .05) to 720 msec +/- 7 for 0.05 mmol/mL gadodiamide and 445 msec +/- 6 for 0.10
      mmol/mL gadodiamide 30 minutes after injection but remained significantly lower
      than those of remote myocardium (879 msec +/- 8). The size of the contrast
      enhanced region increased from 13 mm(2) +/- 2 at 3 minutes to 30 mm(2) +/- 3 at
      30 minutes (P < .05). CONCLUSION: Catheter MR-guided percutaneous intramyocardial
      injection is feasible; after intramyocardial injection of gadodiamide at
      concentrations of 0.05 and 0.10 mmol/mL, T1 values decreased over the observation
      time.

PMID- 15858091
TI  - Effect of thalidomide in hepatocellular carcinoma: assessment with power doppler
      US and analysis of circulating angiogenic factors.
AB  - PURPOSE: To prospectively evaluate the feasibility of using power Doppler
      ultrasonography (US) and measurement of circulating angiogenic factors to assess
      the antiangiogenic effect of thalidomide in hepatocellular carcinoma. MATERIALS
      AND METHODS: The Ethics Committee of the National Taiwan University Hospital
      approved the study, and all patients gave prior written informed consent.
      Evaluation of response to thalidomide treatment was based on findings at computed
      tomography (CT) and change in serum alpha-fetoprotein level. Tumor vascularity
      index was evaluated with power Doppler US in patients with advanced
      hepatocellular carcinoma treated with 200-300 mg/d thalidomide. Serum levels of
      vascular endothelial growth factor, basic fibroblast growth factor, and placental
      growth factor were measured with enzyme-linked immunoassay. The chi(2) test or
      Fisher exact test was used for categorical variables, and the nonparametric Mann
      Whitney test was used for numeric variables. A P value of less than .05 was
      considered to indicate a statistically significant difference. RESULTS: Of 47
      patients enrolled in the study who had disease that was bidimensionally
      assessable on CT scans, 44 were assessable for tumor response. Of the 44
      evaluated, five were classified as showing objective response (responders): One
      each showed a complete and a partial response according to World Health
      Organization criteria, and three had a decrease in alpha-fetoprotein level by
      more than 50% and stable disease for 10.4, 5.3, or 3.5 months. The pretreatment
      vascularity index was significantly higher in responders (median, 7.42; range,
      2.99-13.90) than in nonresponders (median, 2.15; range, 0-25.36) (P = .03). Four
      of five responders had a significant decrease in vascularity index with
      thalidomide. Serum levels of angiogenic factors did not differ significantly
      between responders and nonresponders. CONCLUSION: Higher vascularity index may be
      associated with a better chance of response to thalidomide in patients with
      advanced hepatocellular carcinoma. Serum levels of circulating angiogenic factors
      do not appear to be clinically useful as an indicator of response.

PMID- 15858092
TI  - Minor morphologic abnormalities of adrenal glands at CT: prognostic importance in
      patients with lung cancer.
AB  - PURPOSE: To determine the prognostic importance of minor morphologic
      abnormalities of the adrenal glands at computed tomography (CT) in patients with
      lung cancer. MATERIALS AND METHODS: The study was approved by the committee on
      human research; written informed consent was not required. The authors
      retrospectively identified 197 patients with lung cancer who underwent serial
      chest or abdominal CT and did not have a focal adrenal mass at baseline CT. Two
      readers independently classified the morphologic features of each adrenal gland
      as normal, smoothly enlarged, or nodular at initial CT examination. They
      separately recorded the presence or absence of metastases to the adrenal glands
      (ie, any new focal adrenal mass) at final CT examination; a third independent
      reader arbitrated when interpretations were discordant (n = 11). Multivariate Cox
      proportional hazard models were used to assess for associations between baseline
      adrenal gland morphologic features and subsequent development of adrenal
      metastases. RESULTS: At initial CT, reader 1 classified 253 (64%), 70 (18%), and
      71 (18%) of the 394 adrenal glands and reader 2 classified 258 (65%), 45 (11%),
      and 91 (23%) of these glands as normal, smoothly enlarged, or nodular,
      respectively. The readers had moderate interobserver agreement regarding the
      classification of adrenal gland morphologic features (kappa = 0.54). Metastases
      subsequently developed in 13 adrenal glands in 11 patients. Cox proportional
      hazard models revealed no significant association between baseline adrenal gland
      morphologic features and subsequent development of adrenal metastases (P = .50
      and P = .20 for readers 1 and 2, respectively). CONCLUSION: In patients with lung
      cancer, smooth enlargement or nodularity of the adrenal glands at baseline CT is
      not associated with increased risk of subsequently developing adrenal metastases.

PMID- 15858093
TI  - Effect of human stem cells labeled with ferumoxides-poly-L-lysine on hematologic
      and biochemical measurements in rats.
AB  - PURPOSE: To determine whether ferumoxides-poly-l-lysine (PLL) complex-labeled
      mesenchymal stem cells (MSCs) or ferumoxides-PLL complex alone alters
      hematologic, blood chemistry, renal function, and/or liver function measurements
      after being intravenously infused into rats. MATERIALS AND METHODS: Twenty-five
      rats (group 1) received intravenous injections of labeled MSCs, and 25 additional
      rats (group 2) received intravenous injections of ferumoxides-PLL complex only.
      Complete blood counts, liver and renal function test results, and serum
      electrolyte and iron concentrations were measured for 42 days after the
      injections and compared with those measured in five control rats (group 3). To
      determine the duration of labeled MSCs in the circulation, venous blood was
      serially drawn from five additional rats (group 4) that were injected with
      labeled MSCs. Analyses of variance (ANOVA) followed by Fisher protected least
      significant difference post hoc tests were used to statistically analyze results.
      P < .05 was considered to indicate significance in all analyses. RESULTS:
      Administration of neither labeled MSCs nor ferumoxides-PLL complex had a
      significant effect on hematologic or blood chemistry indicators of organ
      function. Of the parameters measured, only hemoglobin concentration and mean
      corpuscular volume (MCV) in the rats injected with labeled MSCs, as well as MCV
      and hemoglobin, alkaline phosphatase, aspartate aminotransferase, and direct
      bilirubin concentrations in the rats injected with ferumoxides-PLL complex,
      varied significantly during the 42-day postinjection period (P < .05, ANOVA). No
      other measurements, including serum electrolyte and iron concentrations, changed
      significantly during the test period (P > .05). Furthermore, injected labeled
      MSCs had cleared from the peripheral circulation by 15 minutes after injection.
      CONCLUSION: Results indicate that infusing cells that are magnetically labeled
      with ferumoxides-PLL complex into rats does not alter biochemical or hematologic
      measures of organ function in a clinically relevant or preclusive manner.

PMID- 15858094
TI  - CT and MR imaging findings in athletes with early tibial stress injuries:
      comparison with bone scintigraphy findings and emphasis on cortical
      abnormalities.
AB  - PURPOSE: To prospectively compare computed tomography (CT), magnetic resonance
      (MR) imaging, and bone scintigraphy in athletes with clinically suspected early
      stress injury of tibia. MATERIALS AND METHODS: Medical ethics committee approval
      and informed consent were obtained. A total of 42 patients experiencing tibial
      pain due to early stress injuries were evaluated. Eight patients had bilateral
      involvement; thus, 50 tibiae were evaluated. All patients underwent initial
      radiography that was negative for injury. MR imaging, CT, and bone scintigraphy
      were performed in all patients within 1 month of onset of symptoms. Ten
      asymptomatic volunteers served as the control group. Location of stress injuries,
      types of bone alterations, and presence of periosteal and bone marrow edema were
      evaluated. Sensitivity, specificity, accuracy, and positive and negative
      predictive values of MR imaging and CT were assessed, as was sensitivity of bone
      scintigraphy. McNemar test was used to detect statistically significant
      differences. RESULTS: Sensitivity of MR imaging, CT, and bone scintigraphy was
      88%, 42%, and 74%, respectively. Specificity, accuracy, and positive and negative
      predictive values were 100%, 90%, 100%, and 62%, respectively, for MR imaging and
      100%, 52%, 100%, and 26%, respectively, for CT. Significant difference in
      detection of early tibial stress injuries was found between MR imaging and both
      CT and bone scintigraphy (McNemar test; P < .001 and P = .008, respectively).
      CONCLUSION: MR imaging is the single best technique in assessment of patients
      with suspected tibial stress injuries; in some patients with negative MR imaging
      findings, CT can depict osteopenia, which is the earliest finding of fatigue
      cortical bone injury.

PMID- 15858095
TI  - Lumbar disk herniation: do MR imaging findings predict recurrence after surgical
      diskectomy?
AB  - PURPOSE: To retrospectively evaluate if the degree of disk degeneration and disk
      herniation volume at magnetic resonance (MR) imaging are risk factors for
      recurrent disk herniation. MATERIALS AND METHODS: The institutional review board
      permits such retrospective studies, and individual informed consent was not
      required. MR imaging findings obtained before initial diskectomy in 30 patients
      (mean age, 42.8 years; 10 women, 20 men) with recurrent disk herniation (study
      group) and 30 patients (mean age, 42.2 years; nine women, 21 men) without
      recurrence for at least 2 years after surgery (control group) were compared. Disk
      degeneration was assessed on T2-weighted sagittal MR images with a five-point
      grading system (grade I indicated no degeneration; grade II, horizontal
      hypointense bands within disk; grade III, inhomogeneous disk with intermediate
      signal intensity; grade IV, no distinction between inner and outer parts of disk;
      and grade V, collapsed hypointense disk). Disk herniation was classified as
      representing protrusion, extrusion, or sequestration. The volume of both the
      affected intervertebral disk and the herniated disk material was measured.
      Qualitative and quantitative analyses were performed by two readers. The chi(2)
      test was used for comparison of categorical variables. For comparison of disk
      degeneration and volumes between patients with and those without recurrence, a
      paired two-tailed t test was used. Odds ratios based on the extent of disk
      degeneration were calculated for the entire sample. RESULTS: Advanced disk
      degeneration (grades IV and V) was significantly less frequent in the study group
      than in the control group (P < .006). The risk of recurrent disk herniation
      decreased by a factor of 3.4 for each increase in grade of disk degeneration
      (odds ratio: 3.58; 95% confidence interval: 1.3, 9.6; P = .011). Mean disk
      herniation volume as a percentage of intervertebral disk volume was 10.59% +/-
      3.41 in the study group and 11.56% +/- 3.84 in the control group. This difference
      was not significant (P = .31). CONCLUSION: Minor disk degeneration but not
      herniation volume represents a risk factor for the recurrence of disk herniation
      after diskectomy.

PMID- 15858096
TI  - MR imaging in the evaluation of chronic or recurrent headache.
AB  - PURPOSE: To evaluate ability of magnetic resonance (MR) imaging to depict an
      abnormality in patients with chronic or recurrent headache without neurologic
      abnormality. MATERIALS AND METHODS: Institutional review board approval and
      patient informed consent were not required. A total of 306 patients with normal
      neurologic findings and chronic or recurrent headache were examined with MR
      imaging. Patients were divided into three groups: those with no abnormality,
      those with minor abnormality, and those with clinically important intracranial
      abnormality, which may result in chronic or recurrent headache. Literature review
      was also performed. Upper 99.5% confidence bound for frequency of abnormal MR
      findings was calculated. RESULTS: A total of 169 patients (55.2%) were placed in
      the first group, 135 (44.1%) were placed in the second group, and two (0.7%) were
      placed in the third group because they had a clinically important abnormality at
      MR imaging. Neither contrast material enhancement (n = 195) nor repeated MR
      imaging (n = 23) contributed to the diagnosis. Literature review revealed two
      previous studies concerning unspecified headache (in addition to the current
      study), including a total of 1036 MR imaging results and 22 (2.1%) clinically
      important results (upper 99.5% confidence bound, 3.4%). Twelve studies of
      migraine headache were found, with a total of 790 MR imaging examinations.
      Excluding the 19 patients with complicated migraine, the 99.5% confidence bound
      of the frequency of clinically important abnormality at MR imaging was estimated
      as 0.68%. Clinically important infarctions were noted on MR images in five
      (26.3%) of 19 patients with complicated migraine. CONCLUSION: MR imaging is an
      unrewarding technique in the evaluation of patients with chronic or recurrent
      headache and normal neurologic findings. Neither contrast enhancement nor
      repeated MR imaging contributed to diagnosis, although the number of patients in
      the latter category was small.

PMID- 15858097
TI  - Head and neck malignancy: is PET/CT more accurate than PET or CT alone?
AB  - PURPOSE: To prospectively determine whether combined positron emission tomography
      (PET) and computed tomography (CT) is more accurate than either PET or CT alone
      in depicting malignant lesions in the head and neck. MATERIALS AND METHODS: Study
      was approved by the institutional review board, and patient informed consent was
      waived. Sixty-five consecutive patients (42 men, 23 women; age range, 43-83
      years) known to have or suspected of having head and neck cancer were examined
      with combined PET/CT. CT was performed with intravenous administration of a
      contrast agent, and the CT data were used for attenuation correction. Each
      examination was interpreted in three ways: PET images in the absence of CT data,
      CT images in the absence of PET data, and fused PET/CT images. Probability of
      malignancy of each lesion was assigned a score by using a five-point scale.
      Receiver operating characteristic (ROC) analyses were performed by using biopsy,
      imaging, or clinical follow-up as the reference standard. The minimum follow-up
      was 6 months (range, 6-12 months). The results were additionally analyzed to
      assess the degree of radiologist confidence. RESULTS: Follow-up was available for
      64 (98%) of 65 patients. ROC analyses demonstrated that PET/CT is significantly
      superior to PET or CT alone for depiction of malignancy in the head and neck (P <
      .05). In this series, PET/CT had a sensitivity of 98%, a specificity of 92%, and
      an accuracy of 94%. Radiologist confidence was substantially higher with the
      combined modality. CONCLUSION: Combined PET/CT is more accurate than PET or CT
      alone for the depiction of malignancy in the head and neck. Radiologist
      confidence is improved with the combined modality.

PMID- 15858098
TI  - Necrotizing enterocolitis: assessment of bowel viability with color doppler US.
AB  - PURPOSE: To determine whether absence of bowel wall perfusion at color Doppler
      ultrasonography (US) is indicative of bowel necrosis in neonates with necrotizing
      enterocolitis (NEC). MATERIALS AND METHODS: This study was approved by the
      research ethics board, and informed consent was obtained. Sixty-two neonates
      enrolled in the prospective study underwent US of the bowel wall. Neonates were
      divided into two groups. Group A included 30 control subjects with gestational
      ages (GAs) ranging from 24 to 41 weeks. Group B included 32 neonates with GAs
      ranging from 24 to 40 weeks who were clinically proved to have or suspected of
      having NEC. All neonates in group B underwent abdominal radiography. Normative
      values were calculated in group A. In group B, the sensitivities and
      specificities of color Doppler US and abdominal radiography for detection of
      bowel necrosis were computed by using the modified Bell staging criteria for NEC
      as the reference standard. RESULTS: Two neonates were excluded from group B;
      thus, a total of 60 neonates were included in the study. In group A, bowel wall
      thickness ranged from 1.1 to 2.6 mm. Bowel wall perfusion was detected with color
      Doppler US in all 30 neonates. Color Doppler signals ranged from one to nine dots
      per square centimeter. Twenty-two of 30 neonates in group B received a diagnosis
      of NEC. Mild to moderate NEC was diagnosed in 12 neonates. Color Doppler US
      depicted an isolated segment of bowel-absent blood flow in two neonates; this
      finding was confirmed with laparotomy. In 10 neonates with severe NEC, color
      Doppler US depicted isolated or multiple segments of bowel with absent perfusion.
      Pneumoperitoneum was present in only four neonates. The remaining eight neonates
      at risk for NEC had no evidence of loops without perfusion at color Doppler US.
      The sensitivity of free air at abdominal radiography as a positive sign for
      severe NEC with necrotic bowel was 40% compared with the 100% sensitivity of
      absence of flow at color Doppler US (P = .03). CONCLUSION: Color Doppler US is
      more accurate than abdominal radiography in depicting bowel necrosis in NEC.

PMID- 15858099
TI  - Neonatal brain: regional variability of in vivo MR imaging relaxation rates at
      3.0 T--initial experience.
AB  - PURPOSE: To retrospectively investigate regional in vivo magnetic resonance (MR)
      imaging transverse and longitudinal relaxation rates at 3.0 T in neonatal brain,
      the relationship between these rates, and their potential use for gray matter
      (GM) versus white matter (WM) tissue discrimination. MATERIALS AND METHODS:
      Informed parental consent for performance of imaging procedures was obtained in
      each infant. Informed consent for retrospective image analysis was not required;
      ethics approval was obtained from institutional review board. At 3.0 T, R1 and R2
      were measured in brain regions (frontal WM, posterior WM, periventricular WM,
      frontal GM, posterior GM, basal ganglia, and thalamus) in 13 infants with
      suspected neurologic abnormality (two term, 11 preterm). Maps of R1 and R2 were
      acquired with T1 by multiple readout pulses and segmented spin-echo echo-planar
      imaging sequences, respectively. Accuracy of R1 and R2 map acquisition methods
      was tested in phantoms by comparing them with inversion-recovery and spin-echo
      sequences, respectively. Statistical analysis included linear regression analysis
      to determine relationship between R1 and R2 and Wilcoxon signed rank test to
      investigate the potential for discrimination between GM and WM. RESULTS: In
      phantoms, R1 values measured with T1 by multiple readout pulses sequence were 3%
      8% lower than those measured with inversion recovery sequence, and R2 values
      measured with segmented echo-planar sequence were 1%-8% lower than those measured
      with spin-echo sequence. A strong correlation of 0.944 (P < .001) between R1 and
      R2 in neonatal brain was observed. For R2, relative differences between GM and WM
      were larger than were those for R1 (z = -2.366, P < .05). For frontal GM and
      frontal WM, (R2(GM) - R2(WM))/R2(WM) yielded 0.8 +/- 0.2 (mean +/- standard
      deviation) and (R1(GM) - R1(WM))/R1(WM) yielded 0.3 +/- 0.09. CONCLUSION: Results
      at 3.0 T indicate that R1 decreases with increasing field strength, while R2
      values are similar to those reported at lower field strengths. For neonates, R2
      image contrast may be more advantageous than R1 image contrast for
      differentiation between GM and WM.

PMID- 15858100
TI  - The ivory vertebra sign.

PMID- 15858101
TI  - Human peripheral arteries: feasibility of transvenous intravascular MR imaging of
      the arterial wall.
AB  - Feasibility of in vivo transvenous intravascular magnetic resonance (MR) imaging
      of the human arterial wall was determined. All subjects provided written informed
      consent, and institutional review board approved the study. Six arteries in six
      patients were imaged with a guidewire placed in the iliac vein (n = 5) or left
      renal vein (n = 1). Pre- and postcontrast T1-weighted and T2-weighted transvenous
      MR imaging were performed. An atherosclerotic plaque with a fibrous cap was
      identified on 27 (42%) of 64 images of veins without stents; intimal hyperplasia
      in a renal artery with a stent was identified on 12 images. Contrast-to-noise
      ratios (CNRs) on arterial wall postcontrast T1-weighted images were superior to
      those on images obtained with other sequences (P < .001), and the postcontrast
      images demonstrated the greatest number of plaques with a low-signal intensity
      core and fibrous cap. Preliminary results show that transvenous MR imaging is
      feasible for high-spatial-resolution imaging of the arterial wall and
      atherosclerotic plaque. Postcontrast T1-weighted imaging affords greatest CNR for
      the arterial wall.

PMID- 15858102
TI  - Fluorocholine PET/CT in patients with prostate cancer: initial experience.
AB  - Institutional review board approval and written informed consent were obtained.
      Patients with newly diagnosed prostate cancer and patients suspected of having
      recurrent prostate cancer were prospectively evaluated with fluorine 18
      fluorocholine (FCH) combined in-line positron emission tomography (PET) and
      computed tomography (CT). In 19 patients (mean age, 67 years +/- 8; range, 57-85
      years), standardized uptake values of FCH in 17 different tissues were determined
      by using volumes of interest. In nine patients evaluated at initial staging,
      histologic findings of the resected prostate were compared to FCH uptake. Only
      small variations of physiologic tracer accumulation were measured in all organs
      but the kidneys. Differentiation of benign hyperplasia from cancerous prostate
      lesions was not possible with FCH PET/CT. However, in patients with recurrent
      prostate cancer, FCH PET/CT is a promising imaging modality for detecting local
      recurrence and lymph node metastases.

PMID- 15858103
TI  - Gustatory stimulation changes the apparent diffusion coefficient of salivary
      glands: initial experience.
AB  - Echo-planar diffusion-weighted (DW) magnetic resonance (MR) imaging was used to
      evaluate changes in the parotid glands during gustatory stimulation. The study
      protocol was approved by the local ethics committee, and informed consent was
      obtained from all volunteers. Twelve healthy volunteers (five women, seven men)
      with a median age of 25 years (range, 22-30 years) were examined with a 1.5-T MR
      unit. A DW MR imaging sequence was performed once at rest and continuously
      repeated over a mean period of 26 minutes (range, 24-28 minutes) during salivary
      stimulation with a tablet of ascorbic acid given orally. During the first 5
      minutes (range, 1 minute 30 seconds--7 minutes 30 seconds) of salivary
      stimulation, a decrease in apparent diffusion coefficient (ADC) was observed in
      both the parotid (P = .0001) and the submandibular (P = .0004) glands in all
      volunteers. During the following 15 minutes, a steady increase in ADC from the
      baseline value was noted for the parotid glands (P = .0022), and peak ADC was
      reached a median of 21 minutes (range, 14-21 minutes) after the start of
      gustatory stimulation. The ADC of the submandibular glands did not increase
      significantly after the start of gustatory stimulation compared with the ADC at
      baseline. In conclusion, DW MR imaging allows physicians to noninvasively
      demonstrate functional changes in the salivary glands.

PMID- 15858104
TI  - Flat-panel-detector chest radiography: effect of tube voltage on image quality.
AB  - PURPOSE: To compare the visibility of anatomic structures in direct-detector
      chest radiographs acquired with different tube voltages at equal effective doses
      to the patient. MATERIALS AND METHODS: The study protocol was approved by the
      institutional internal review board, and written informed consent was obtained
      from all patients. Posteroanterior chest radiographs of 48 consecutively selected
      patients were obtained at 90, 121, and 150 kVp by using a flat-panel-detector
      unit that was based on cesium iodide technology and automated exposure control.
      Monte Carlo simulations were used to verify that the effective dose for all
      kilovoltage settings was equal. Five radiologists subjectively and independently
      rated the delineation of anatomic structures on hard-copy images by using a five
      point scale. They also ranked image quality in a blinded side-by-side comparison.
      Average ranking scores were compared by using one-way analysis of variance with
      repeated measures. Data were analyzed for the entire patient group and for two
      patient subgroups that were formed according to body mass index (BMI). RESULTS:
      The visibility scores of most anatomic structures were significantly superior
      with the 90-kVp images (mean score, 3.11), followed by the 121-kVp (mean score,
      2.95) and 150-kVp images (mean score, 2.80). Differences did not reach
      significance (P > .05) only for the delineation of the peripheral vessels, the
      heart contours, and the carina. This was also true for the subgroup of patients
      (n = 24) with a BMI greater than and the subgroup of patients (n = 24) with a BMI
      less than the mean BMI (26.9 kg/m(2)). At side-by-side comparison, the readers
      rated 90-kVp images as having superior image quality in the majority of image
      triplets; the percentage of 90-kVp images rated as "first choice" ranged from 60%
      (29 of 48 patients) to 90% (43 of 48 patients), with a median of 88% (42 of 48
      patients), among the readers. CONCLUSION: Delineation of most anatomic structures
      and overall image quality were ranked superior in digital radiographs acquired
      with lower kilovoltage at a constant effective patient dose.

PMID- 15858105
TI  - Advanced hepatocellular carcinoma: treatment with high-intensity focused
      ultrasound ablation combined with transcatheter arterial embolization.
AB  - PURPOSE: To evaluate ultrasonographically (US)-guided high-intensity focused
      ultrasound ablation combined with transcatheter arterial chemoembolization (TACE)
      in the treatment of stage IVA hepatocellular carcinoma (HCC). MATERIALS AND
      METHODS: Institutional review board approval and informed consent were obtained.
      From November 1998 to May 2000, 50 consecutive patients with stage IVA HCC (TNM
      classification, T4N0-1M0) were alternately enrolled in one of two treatment
      groups: group 1 (n = 26), in which TACE was performed alone, and group 2 (n =
      24), in which transcutaneous ablation of HCC with high-intensity focused
      ultrasound was performed 2-4 weeks after TACE. The tumors were 4-14 cm in
      diameter (mean, 10.5 cm). Immediate therapeutic effects were assessed at follow
      up with Doppler US and computed tomography or magnetic resonance imaging. All
      patients were followed up for 3-24 months (mean, 8 months) to observe long-term
      therapeutic effects and complications in both groups. Tumor reduction rates,
      median survival time, and cumulative survival rates in both groups were
      calculated by using the unpaired Student t test and Kaplan-Meier method. RESULTS:
      No severe complication was observed after focused ultrasound ablation, and no
      unexpected side effects were noted after TACE. Follow-up images showed absence or
      reduction of blood supply in the lesions after focused ultrasound ablation when
      compared with blood supply after TACE alone. The median survival time was 11.3
      months in group 2 and 4.0 months in group 1 (P = .004). The 6-month survival rate
      was 80.4%-85.4% in group 2 and 13.2% in group 1 (P = .002), and the 1-year
      survival rate was 42.9% and 0%, respectively. Median reductions in tumor size as
      a percentage of initial tumor volume at 1, 3, 6, and 12 months after treatment,
      respectively, were 28.6%, 35.0%, 50.0%, and 50.0% in group 2 and 4.8%, 7.7%,
      10.0%, and 0% in group 1 (P < .01). CONCLUSION: The combination of high-intensity
      focused ultrasound ablation and TACE is a promising approach in patients with
      advanced-stage HCC, but large-scale randomized clinical trials are necessary for
      confirmation.

PMID- 15858106
TI  - Ethanol embolization of arteriovenous malformations: interim results.
AB  - PURPOSE: To assess retrospectively the interim results and the complications of
      ethanol embolization treatment of arteriovenous malformations (AVMs). MATERIALS
      AND METHODS: Institutional review board approval was obtained for a retrospective
      review of patient medical and imaging records. Informed consent was not required
      by the institutional review board. Written consent for the procedure was obtained
      from all patients after a discussion about the advantages and risks of the
      procedure. After a general anesthetic was administered, 40 patients (16 male, 24
      female; age range, 9-53 years) with inoperable AVMs in the body and extremities
      underwent staged ethanol embolizations (range, 1-24; median, 3). Pulmonary artery
      pressure and arterial blood pressure were monitored as ethanol was injected.
      Ethanol embolizations (50%-100% ethanol mixed with nonionic contrast material)
      were performed by using transcatheter and/or direct puncture techniques. Ten
      patients underwent additional coil deployment during ethanol embolization.
      Clinical follow-up (range, 2-48 months; mean, 14.6 months; median, 12 months) was
      performed in all patients, and results from imaging follow-up (range, 0-48
      months; mean, 8.4 months; median, 6 months) were available from the last
      treatment session in 28 patients. Therapeutic outcomes were established by
      evaluating the clinical outcome of symptoms and signs, as well as the degree of
      devascularization at follow-up angiography. RESULTS: One hundred seventy-five
      ethanol embolizations were performed in 40 patients. Sixteen (40%) of 40 patients
      were cured, 11 (28%) had partial remission, seven (18%) had no remission, and one
      (2%) experienced aggravation. Treatment failed in five patients (12%). Ethanol
      embolization was considered effective (cure, 16 patients; partial remission, 11
      patients) in 27 patients (68%). Eleven patients will need further treatment
      sessions for residual AVMs. Twenty-one patients (52%) experienced complications.
      Twenty-seven minor complications (skin and transient peripheral nerve injuries)
      (27 [15%] of 175 procedures) occurred in 18 (45%) of 40 patients. All minor
      complications were healed with wound dressing and observation. Five major
      complications (five [3%] of 175 procedures) occurred in five (12%) of 40
      patients, and four patients recovered completely. CONCLUSION: Ethanol
      embolization has the potential for cure in the management of AVMs of the body and
      extremities but with acceptable risk of minor and major complications.

PMID- 15858107
TI  - Peripheral arterial disease: comparison of color duplex US and contrast-enhanced
      MR angiography for diagnosis.
AB  - PURPOSE: To prospectively compare the diagnostic accuracies of color duplex
      ultrasonography (US) and contrast material-enhanced magnetic resonance (MR)
      angiography and to assess interobserver agreement regarding contrast-enhanced MR
      angiographic findings in patients suspected of having peripheral arterial disease
      (PAD). MATERIALS AND METHODS: The institutional review board approved the study,
      and all patients provided signed informed consent. Two hundred ninety-five
      patients referred for diagnostic and preinterventional work-up of PAD with duplex
      US also underwent gadolinium-enhanced MR angiography. Data sets were reviewed for
      presence or absence of 50% or greater luminal reduction, which indicated
      hemodynamically significant stenosis, and to determine interobserver agreement.
      At duplex US, a peak systolic velocity ratio of 2.5 or greater indicated
      significant stenosis. Primary outcome measures were differences between duplex US
      and contrast-enhanced MR angiography in sensitivity and specificity for detection
      of significant stenosis, as assessed with the McNemar test, and interobserver
      agreement between the two contrast-enhanced MR angiogram readings, expressed as
      quadratic weighted kappa values. Intraarterial digital subtraction angiography
      (DSA) was the reference standard. RESULTS: Two hundred forty-nine patients had at
      least one hemodynamically significant stenotic lesion at contrast-enhanced MR
      angiography, duplex US, or both examinations. One hundred fifty-two patients
      underwent intraarterial DSA. The quadratic weighted kappa for agreement regarding
      the presence of 50% or greater stenosis at contrast-enhanced MR angiography was
      0.89 (95% confidence interval [CI]: 0.87, 0.91). Sensitivity of duplex US was 76%
      (95% CI: 69%, 82%); specificity, 93% (95% CI: 91%, 95%); and accuracy, 89%.
      Sensitivity and specificity of contrast-enhanced MR angiography were 84% (95% CI:
      78%, 89%) and 97% (95% CI: 95%, 98%), respectively; accuracy was 94%. Sensitivity
      (P = .002) and specificity (P = .03) of contrast-enhanced MR angiography were
      significantly higher. CONCLUSION: Results of this prospective comparison between
      contrast-enhanced MR angiography and duplex US provide evidence that contrast
      enhanced MR angiography is more sensitive and specific for diagnosis and
      preinterventional work-up of PAD.

PMID- 15858108
TI  - Increased brain cancer risk in physicians with high radiation exposure.

PMID- 15858109
TI  - Can intrauterine devices actually be considered safe at 3-T MR imaging?

PMID- 15858110
TI  - Conventional angiography remains an important tool for measurement of carotid
      arterial stenosis.

PMID- 15858111
TI  - Frozen shoulder.

PMID- 15858112
TI  - Screening for thyroid disease in pregnancy.
AB  - Although gestational hyperthyroidism is uncommon (0.2%), hypothyroidism
      (autoimmune disease or suboptimal iodine intake) occurs in 2.5% of women and is
      predictive of reduced neonatal and child neuropsychological development and
      maternal obstetric complications. Postpartum thyroid dysfunction (PPTD) occurs in
      5-9% of women and is associated with antithyroid peroxidase antibodies
      (antiTPOAb) in 10% of women in early pregnancy. Therefore, screening for thyroid
      dysfunction in pregnancy should be considered. T4 and thyroid stimulating hormone
      measurements could be used to screen for hypothyroidism, which would require
      levothyroxine intervention treatment. T4 supply is crucial to fetal nervous
      system maturation; currently, the recommended daily iodine intake is 200 microg,
      and this is not always achieved, even in the UK. At present, a randomised
      prospective trial is ongoing to provide the evidence base for this screening
      strategy. Meanwhile, it is reasonable to (a) optimise iodine nutrition during
      pregnancy; (b) ascertain women with known thyroid disease; (c) identify women at
      increased risk of thyroid disease-for example, those with other autoimmune
      diseases. PPTD can be predicted by measurement of antiTPOAb in early gestation.

PMID- 15858113
TI  - Melanocytic dysplastic naevi occupy the middle ground between benign melanocytic
      naevi and cutaneous malignant melanomas: emerging clues.
AB  - Although several studies have confirmed the aetiological importance of
      melanocytic dysplastic naevi (MDN) in the development of cutaneous malignant
      melanoma (CMM), the analysis of these lesions was directed mostly towards the
      study of melanomas. The underlying reasons include the relatively large size of
      CMMs, their direct lethal outcome, and the feasibility of establishing melanoma
      cell lines. In contrast, because of their relatively small size, questionable
      malignant potential, and the difficulty in establishing in vitro cultures, MDN
      have been studied less extensively. Hypothetically, transformed melanocytes can
      give rise to any lesion in the hierarchy of melanocytic tumours. Based on this
      hypothetical perspective, and on the epidemiological, morphological,
      immunohistochemical, and genetic characteristics of MDN, it is not surprising
      that these lesions occupy an intermediate position in the hierarchy of
      melanocytic lesions, and may be precursors of CMM. Although this argument appears
      to be straightforward, it is still controversial. This review explores the
      components of this argument and provides supporting evidence for this hypothesis.

PMID- 15858114
TI  - Unnecessary repeat requesting of tests: an audit in a government hospital
      immunology laboratory.
AB  - Unnecessary repeat requesting of tests can make up a large proportion of a
      laboratory's workload. This audit set out to establish the size of this problem
      and to identify the circumstances under which these repeat requests were made in
      a government tertiary hospital immunology laboratory. The numbers of tests for
      immunoglobulin measurement, common autoantibodies, and tumour markers that were
      repeated over a 12 month period were analysed by interrogating the Delphic
      laboratory computer system using a management information system for raw data
      enquiry protocol. Repeat requests within 12 weeks of a previous request made up
      16.78% of the total workload. The total cost of the tests was estimated at 132
      151 US dollars. The waste of technician time and reagents as a result of
      unnecessary repeat testing is excessive. Many of these tests might be eliminated
      with the use of interventions such as computerised reminders.

PMID- 15858115
TI  - Report and abstracts of the 3rd International Workshop on the CCN Family of
      Genes. St Malo, France, 20-23 October 2004.

PMID- 15858117
TI  - Denaturing high performance liquid chromatography: high throughput mutation
      screening in familial hypertrophic cardiomyopathy and SNP genotyping in motor
      neurone disease.
AB  - AIMS: To evaluate the usefulness of denaturing high performance liquid
      chromatography (DHPLC) as a high throughput tool in: (1) DNA mutation detection
      in familial hypertrophic cardiomyopathy (FHC), and (2) single nucleotide
      polymorphism (SNP) discovery and validation in sporadic motor neurone disease
      (MND). METHODS: The coding sequence and intron-exon boundaries of the cardiac
      beta myosin heavy chain gene (MYH7) were screened by DHPLC for mutation
      identification in 150 unrelated patients diagnosed with FHC. One hundred and
      forty patients with sporadic MND were genotyped for the A67T SNP in the
      poliovirus receptor gene. All DHPLC positive signals were confirmed by
      conventional methods. RESULTS: Mutation screening of MYH7 covered 10 kb with a
      total of 5700 amplicons, and more than 6750 DHPLC injections were completed
      within 35 days. The causative mutation was identified in 14% of FHC cases,
      including seven novel missense mutations (L227V, E328G, K351E, V411I, M435T,
      E894G, and E927K). Genotyping of the A67T SNP was performed at two different
      temperatures both in MND cases and 280 controls. This coding SNP was found more
      frequently in MND cases (13.6%) than in controls (6.8%). Furthermore, 19 and two
      SNPs were identified in MYH7 and the poliovirus receptor gene, respectively,
      during DHPLC screening. CONCLUSIONS: DHPLC is a high throughput, sensitive,
      specific, and robust platform for the detection of DNA variants, such as disease
      causing mutations or SNPs. It enables rapid and accurate screening of large
      genomic regions.

PMID- 15858118
TI  - Analysis of Bcl-2 protein expression in choroidal melanomas.
AB  - BACKGROUND: Bcl-2 protooncogene alterations are involved in tumorigenesis and may
      have prognostic ramifications. AIMS: To investigate normal ocular structures and
      choroidal melanoma for: (1) Bcl-2 protein expression (semiquantitative staining
      values: SI, staining intensity; PP, percentage of positive cells; and IRS,
      immunoreactivity score) and (2) any associations between the staining values and
      clinicopathological features in these lesions. MATERIALS/METHODS: Bcl-2 protein
      expression was analysed in 24 choroidal melanomas using immunoperoxidase staining
      methods. RESULTS: Bcl-2 protein expression was seen in corneal epithelium, lens
      epithelium, the ciliary body, and retinal cells. In these structures, the mean
      (SEM) values were: 1.1 (0.1), 1.6 (0.3), 1.1 (0.1), and 2.3 (0.3), respectively,
      for SI; 1.6 (0.2), 1.7 (0.1), 1.7 (0.2), and 1.7 (0.2) for PP, respectively; and
      1.9 (0.4), 2.7 (0.5), 1.9 (0.1), and 4.0 (0.8), respectively, for IRS. Based on
      Bcl-2 immunoreactivity, the lesions were divided into two groups. The first group
      comprised 12 tumours with Bcl-2 expression. Bcl-2 expression was significantly
      higher in this group compared with normal ocular structures (1.5 (0.1) v 2.8
      (0.2), 1.7 (0.1) v 3.5 (0.1), and 2.6 (0.3) v 9.3 (0.9) for mean (SEM) SI, PP,
      and IRS scores, respectively; p = 0.00). The second group comprised 12 tumours
      lacking Bcl-2 protein expression. There was no significant correlation between
      Bcl-2 protein expression and most of the clinicopathological features of these
      lesions. CONCLUSIONS: Bcl-2 protein expression is altered in choroidal melanomas.

PMID- 15858119
TI  - A study to determine plasma antioxidant concentrations in patients with Barrett's
      oesophagus.
AB  - BACKGROUND: Dietary questionnaire studies have suggested that patients with
      oesophageal adenocarcinoma are deficient in antioxidants. It is not known whether
      the same holds true for patients with the precursor lesion, Barrett's oesophagus.
      AIMS: To evaluate the hypothesis that patients with Barrett's oesophagus are
      deficient in antioxidants compared with patients without evidence of Barrett's
      oesophagus. PATIENTS AND METHODS: Plasma antioxidant profiles (copper, selenium,
      zinc; vitamins A, C, and E; carotenoids) were determined for patients with
      Barrett's oesophagus (n = 36), patients with erosive oesophagitis (n = 32), and
      patient controls (n = 35). RESULTS: Patients with Barrett's oesophagus had
      significantly lower plasma concentrations of selenium, vitamin C, beta
      cryptoxanthine, and xanthophyll compared with the other groups. CONCLUSIONS: This
      study confirms the hypothesis that patients with Barrett's oesophagus are
      deficient in certain antioxidants.

PMID- 15858120
TI  - A novel BRCA2 mutation in an Indonesian family found with a new, rapid, and
      sensitive mutation detection method based on pooled denaturing gradient gel
      electrophoresis and targeted sequencing.
AB  - BACKGROUND: Breast cancer is increasing in Indonesia and other developing
      countries. Germline mutations in the BRCA1/2 genes are most strongly associated
      with a high risk for breast cancer development. There have been no reports on
      BRCA1/2 gene mutations in the Indonesian population. Genetic research yielding
      insight into mutations affecting the Indonesian population can help in risk
      assessment of individual patients. AIMS: To screen the BRCA1/2 genes for
      mutations in early onset Indonesian breast cancer patients and their families
      with a new, simple, and sensitive BRCA1/2 mutation screening strategy based on
      denaturing gradient gel electrophoresis (DGGE) and targeted sequencing. METHODS:
      DNA was isolated from the blood of four Indonesian breast cancer patients from
      high risk families and seven family members, and the polymerase chain reaction
      was performed with specially designed primers throughout the BRCA1/2 coding
      sequences to produce fragments suitable for pooled DGGE analysis. The aberrantly
      migrating samples were reamplified and sequenced. RESULTS: Two mutations were
      found in exons 13 and 16 of BRCA1 and two mutations in exons 2 and 14 of BRCA2,
      which turned out to be established polymorphisms according to the Breast Cancer
      Information Core. In addition, a novel 6 bp deletion in exon 11, leading to a
      premature stop, was found in BRCA2. CONCLUSION: Pooled DGGE and targeted
      sequencing revealed four BRCA1/2 polymorphisms and one novel BRCA2 mutation in a
      group of Indonesian patients at high risk of hereditary breast cancer. This
      illustrates that the proposed method is sensitive and particularly suited for
      screening unknown populations.

PMID- 15858121
TI  - Overexpression/amplification of HER-2/neu is uncommon in hepatocellular
      carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent fatal
      cancers in the world. Despite advances in early diagnosis and improvements in
      surgical techniques, the survival of patients with HCC even after resection is
      poor because of the high incidence of recurrences. Therefore, the identification
      of prognostic factors may be helpful in the development of new treatment
      protocols. AIMS: To investigate HER-2/neu status in HCC by immunohistochemistry
      (IHC) and fluorescence in situ hybridisation (FISH), and to explore the
      possibility of using trastuzumab in the treatment of HCC. METHODS: Eight hundred
      and sixty eight surgical samples from patients with primary HCC were examined for
      their HER-2/neu status. IHC for HER-2/neu was performed with the HercepTest kit;
      FISH analysis was performed with the PathVysion HER-2 DNA probe kit. The
      correlations between HER-2/neu overexpression and clinicopathological
      characteristics were analysed statistically. RESULTS: HER-2/neu overexpression
      was detected in 21 (2.42%) of the 868 primary HCCs. Only one specimen showed HER
      2/neu gene amplification by FISH. No significant associations were found between
      HER-2/neu overexpression and the clinicopathological parameters. CONCLUSIONS:
      There is a low frequency of HER-2/neu overexpression/amplification in HCC. There
      appears to be no role for HER-2/neu as a prognostic marker and no benefit of anti
      HER-2/neu trastuzumab treatment in patients with HCC.

PMID- 15858122
TI  - Processing of radical prostatectomy specimens for correlation of data from
      histopathological, molecular biological, and radiological studies: a new whole
      organ technique.
AB  - AIMS: To develop a method of processing non-formalin fixed prostate specimens
      removed at radical prostatectomy to obtain fresh tissue for research and for
      correlating diagnostic and molecular results with preoperative imaging.
      METHODS/RESULTS: The method involves a prostate slicing apparatus comprising a
      tissue slicer with a series of juxtaposed planar stainless steel blades linked to
      a support, and a cradle adapted to grip the tissue sample and receive the blades.
      The fresh prostate gland is held in the cradle and the blades are moved through
      the cradle slits to produce multiple 4 mm slices of the gland in a plane
      perpendicular to its posterior surface. One of the resulting slices is preserved
      in RNAlater. The areas comprising tumour and normal glands within this preserved
      slice can be identified by matching it to the haematoxylin and eosin stained
      sections of the adjacent slices that are formalin fixed and paraffin wax
      embedded. Intact RNA can be extracted from the identified tumour and normal
      glands within the RNAlater preserved slice. Preoperative imaging studies are
      acquired with the angulation of axial images chosen to be similar to the slicing
      axis, such that stained sections from the formalin fixed, paraffin wax embedded
      slices match their counterparts on imaging. CONCLUSIONS: A novel method of
      sampling fresh prostate removed at radical prostatectomy that allows tissue
      samples to be used both for diagnosis and molecular analysis is described. This
      method also allows the integration of preoperative imaging data with
      histopathological and molecular data obtained from the prostate tissue slices.

PMID- 15858123
TI  - Expression and gene amplification of primary (A, B1, D1, D3, and E) and secondary
      (C and H) cyclins in colon adenocarcinomas and correlation with patient outcome.
AB  - BACKGROUND/AIMS: Deregulation of cell cycle control is a hallmark of cancer. The
      primary cyclins (A, B1, D1, D3, and E) are crucial for cell cycle progression.
      Secondary cyclins (C and H) have putative indirect effects on cell cycle
      progression and have not previously been evaluated in colon cancer. This study
      examined cyclin protein expression and gene amplification in colon adenocarcinoma
      and the correlation with patient outcome. METHODS: Immunohistochemistry and real
      time quantitative polymerase chain reaction were used to determine cyclin
      expression and gene amplification in 219 tumours. The results were compared with
      clinical variables and patient outcomes. RESULTS: Cyclin H was overexpressed in
      all tumours, cyclin C in 88%, cyclin B1 in 58%, cyclin A in 83%, cyclin D3 in
      36%, cyclin E in 25%, and cyclin D1 in 11% of the tumours. Extra gene copies of
      cyclin A were seen in 6.2% of the tumours, cyclin B1 in 9%, cyclin C in 26.9%,
      cyclin D1 in 55%, cyclin D3 in 20.5%, cyclin E in 19.1%, and cyclin H in 5.1%. A
      significant correlation between protein overexpression and gene amplification was
      seen for cyclin C only. High expression of cyclin A was independently associated
      with improved survival. Amplification of cyclin C was independently associated
      with an unfavourable prognosis. CONCLUSIONS: Amplification of the cyclin C gene
      was related to an unfavourable prognosis and high protein expression of cyclin A
      was associated with a better outcome in colon adenocarcinoma.

PMID- 15858124
TI  - Expression of secreted Wnt antagonists in gastrointestinal tissues: potential
      role in stem cell homeostasis.
AB  - BACKGROUND: Wnt signalling dysregulation has been implicated in cancer, including
      colon and gastric cancer. Initiation of Wnt signalling is modulated by soluble
      Wnt antagonists (sWAs), including soluble frizzled related proteins, dickkopf
      (Dkk) proteins, and Wnt inhibitory factor-1 (Wif1). AIMS: To evaluate the role of
      sWAs in upper (gastric) and lower (colon) gastrointestinal tract tumorigenesis.
      METHODS: Dkk1-3, Wif1, and FrzB expression was evaluated by in situ RNA
      hybridisation on normal and malignant human gastric and colon tissues. Expression
      was graded semiquantitatively. RESULTS: Wif1, Dkk1, and Dkk2 were not expressed
      in normal gastric tissue. Dkk3 was expressed in some samples, with stronger
      expression in deep gastric glands. FrzB was expressed in several normal gastric
      samples, but not in matched tumour specimens. In contrast, Dkk1 and FrzB were not
      expressed in normal colon. Wif1 was expressed in most colon samples, with
      stronger expression at crypt bases. Dkk3 and Dkk2 expression was also
      concentrated at crypt bases. There were no differences between sWA expression in
      malignant colon and matched normal tissue. CONCLUSIONS: sWA expression differed
      between upper and lower gastrointestinal tract. The loss of FrzB in gastric
      cancer suggests that it acts as a tumour suppressor. The graded expression of
      Dkk3 in gastric tissue, and Dkk2, Dkk3, and Wif1 in colon tissue, with increased
      expression in the deep gastric glands/colonic crypt bases, where gastrointestinal
      stem cells reside, suggests that sWAs may be crucial Wnt signalling regulators in
      these tissues, and may contribute to stem cell pool maintenance. sWAs are
      important components of the gastrointestinal proliferative regulatory network.

PMID- 15858125
TI  - High expression of Mcl-1 in ALK positive and negative anaplastic large cell
      lymphoma.
AB  - AIM: To gain more insight into the genes involved in the aetiology and
      pathogenesis of anaplastic large cell lymphoma (ALCL). METHODS: Serial analysis
      of gene expression (SAGE) was undertaken on the CD4+ALK+ (anaplastic lymphoma
      kinase positive) ALCL derived cell line Karpas299 and as comparison on CD4+ T
      cells. Quantitative reverse transcription polymerase chain reaction (RT-PCR) and
      immunohistochemistry were performed on five ALCL derived cell lines and 32 tissue
      samples to confirm the SAGE data. RESULTS: High expression of Mcl-1 was seen in
      the Karpas299 cell line, whereas the two other antiapoptotic Bcl-2 family
      members, Bcl-2 and Bcl-X(L), were not detected in the SAGE library. Quantitative
      RT-PCR confirmed the high expression of Mcl-1 mRNA and low expression of Bcl-2
      and Bcl-X(L) in Karpas299 and in four other ALCL cell lines. To expand on these
      initial observations, primary tissue samples were analysed for Mcl-1, Bcl-X(L),
      and Bcl-2 by immunohistochemistry. All 23 ALK+ and nine ALK- ALCL cases were
      positive for Mcl-1. Bcl-2 and Bcl-X(L) were expressed infrequently in ALK+ ALCL
      cases, but were present in a higher proportion of ALK- ALCL cases. CONCLUSION:
      The consistent high expression of Mcl-1 in ALK+ and ALK- ALCL suggests that Mcl-1
      is the main antiapoptotic protein in this disease. The high frequency of Mcl-1,
      Bcl-2, and Bcl-X(L) positive ALCL cases in the ALK- group compared with the ALK+
      group indicates that ALK induced STAT3 activation is not the main regulatory
      pathway in ALCL.

PMID- 15858126
TI  - p16INK4A, CDC6, and MCM5: predictive biomarkers in cervical preinvasive neoplasia
      and cervical cancer.
AB  - AIM: To analyse and compare expression patterns of three potential biomarkers
      p16(INK4A), CDC6, and MCM5-and evaluate their use as predictive biomarkers in
      squamous and glandular cervical preinvasive neoplasia. METHODS:
      Immunocytochemical analysis of p16(INK4A), MCM5, and CDC6 expression was
      performed on 20 normal, 38 cervical intraepithelial neoplasia 1 (CIN1), 33 CIN2,
      46 CIN3, 10 squamous cell carcinoma, 19 cervical glandular intraepithelial
      neoplasia (cGIN), and 10 adenocarcinoma samples. Staining intensity was assessed
      using a 0-3 scoring system. p16(INK4A), MCM5, and CDC6 expression was also
      examined in ThinPrep slides exhibiting mild, moderate, and severe dyskaryosis.
      Human papillomavirus (HPV) was detected using a modified SYBR green assay.
      Fluorogenic polymerase chain reaction (PCR) and solution phase PCR were used for
      specific HPV typing. RESULTS: All three markers showed a linear correlation
      between expression and grade of dysplasia. p16(INK4A) and MCM5 protein expression
      was upregulated in all grades of squamous and glandular dysplasia. CDC6 protein
      was preferentially expressed in high grade lesions and in invasive squamous cell
      carcinoma. CONCLUSION: p16(INK4A) expression was closely associated with high
      risk HPV infection-all grades of squamous and glandular cervical lesions were
      immunohistochemically positive. MCM5 staining intensity was independent of high
      risk HPV infection, highlighting its potential as a biomarker in both HPV
      dependent and independent cervical dysplasia. CDC6 may be a biomarker of high
      grade and invasive lesions of the cervix, with limited use in low grade
      dysplasia. p16(INK4A) was the most reliable marker of cervical dysplasia.
      Combinations of dysplastic biomarkers may be useful in difficult diagnostic
      cases.

PMID- 15858127
TI  - Cyclooxygenase 2 expression in nasopharyngeal carcinoma: immunohistochemical
      findings and potential implications.
AB  - BACKGROUND: Cyclooxygenase 2 (COX-2), an inducible prostaglandin synthase,
      participates in inflammatory and neoplastic processes. It is expressed by various
      tumours and contributes to carcinogenesis. Notably, COX-2 inhibitors appear to
      have tumour suppressor effects and are being evaluated in clinical trials. AIMS:
      To investigate COX-2 expression in nasopharyngeal carcinoma (NPC), a common
      tumour in parts of Asia, and to discuss potential implications. METHODS: Eighty
      five cases of NPC were reviewed. COX-2 immunohistochemistry and semiquantitative
      assessment of expression in nasopharyngeal biopsies were performed. Because COX-2
      is proangiogenic, tumour microvessel density was also assessed with the use of
      CD31 immunohistochemistry. RESULTS: Histologically, 78 NPCs were
      undifferentiated, six were non-keratinising, and one was keratinising. Thirty
      nine NPCs had adjacent dysplastic epithelium. COX-2 expression was noted in 60
      NPCs, 14 of 39 samples of dysplastic epithelium, and only one of 25 samples of
      normal epithelium (p < 0.01). Microvessel density was not significantly different
      between COX-2 positive and COX-2 negative tumours (p = 0.774). Tumour COX-2
      positivity was not associated with higher tumour stage (p = 0.423). CONCLUSION:
      COX-2 expression is more frequently seen as nasopharyngeal epithelium progresses
      from normal to dysplastic to carcinoma. This suggests that COX-2 contributes to
      the multistep process of NPC carcinogenesis. COX-2 represents a therapeutic
      target for COX-2 inhibitors, and there is thus a basis for the further
      investigation of this adjuvant treatment modality for NPC. COX-2 inhibitors are
      known to potentiate the antitumour effects of radiotherapy, which is the primary
      treatment for NPC.

PMID- 15858128
TI  - Primary local orbital amyloidosis: biochemical identification of the
      immunoglobulin light chain kappaIII subtype in a small formalin fixed, paraffin
      wax embedded tissue sample.
AB  - BACKGROUND: Amyloidosis refers to a heterogeneous group of disorders associated
      with the deposition of chemically distinct amyloid fibril proteins. Precise
      determination of chemical amyloid type has diagnostic, therapeutic, and
      prognostic relevance. Although immunohistochemical techniques are used routinely
      to determine the amyloid type, the results can be negative or inconclusive, so
      that biochemical characterisation is often required. The development and
      application of new biochemical microtechniques suitable for examination of
      extremely small tissue samples is essential for precise identification of the
      deposited amyloid proteins. AIMS: To investigate biochemically the amyloid
      proteins present in a formalin fixed paraffin wax embedded orbital tissue from a
      patient with localised orbital amyloidosis in whom immunohistochemistry was not
      helpful in the determination of amyloid type. METHODS: Extraction of amyloid
      proteins from fixed tissue and their identification was carried out by a recently
      developed microtechnique. An extremely small tissue sample was dewaxed and
      extracted with formic acid. The extracted material was analysed using
      electrophoresis, western blotting, and amino acid sequencing. RESULTS:
      Biochemical examination of the extracted proteins showed the presence of
      immunoglobulin (Ig) derived amyloid proteins, which were composed of the N
      terminal fragments of the Ig light chain kappaIII subtype (AL-kappaIII) (16, 8,
      and 3 kDa). CONCLUSIONS: This is the first chemically proved AL case reported in
      association with primary localised orbital amyloidosis. The biochemical
      microtechnique used was useful in achieving a precise diagnosis of amyloid
      disease, in a case where the results of routine immunohistochemical examination
      of amyloid were inconclusive.

PMID- 15858129
TI  - Sections of the nipple and quadrants in mastectomy specimens for carcinoma are of
      limited value.
AB  - AIM: To assess the value of nipple and quadrant sections in mastectomy specimens
      for carcinoma in detecting Paget's disease and multifocal carcinoma. METHODS: Two
      hundred and forty eight consecutive mastectomies performed for carcinoma were
      reviewed. The presence of Paget's disease of the nipple and mode of
      identification of any multifocal carcinoma was recorded. RESULTS: Nipple sections
      showed Paget's disease in eight specimens: in five the diagnosis had been made on
      previous biopsy and in three (1%) this was a new diagnosis. In the 220 specimens
      in which all four quadrants were sampled, multifocal disease was identified more
      often in specimens with invasive carcinoma (39 of 186; 21%) than in those with
      only ductal carcinoma in situ (0 of 34). In specimens with invasive carcinoma,
      multifocality was identified macroscopically in 20: on microscopy of tumour
      sections in four, on microscopic examination of quadrant sections in 11, in the
      nipple in three, and in both quadrant and nipple sections in one. Overall,
      multifocality was found on microscopic examination of quadrant or nipple sections
      in 15 of 220 specimens (7%). CONCLUSIONS: The low frequency of detection of
      multifocality or Paget's disease in nipple and quadrant sections from mastectomy
      specimens, combined with the fact that such findings do not affect patient
      management, suggest that nipple and quadrant sections should only be taken if
      resources permit.

PMID- 15858130
TI  - Primary antibody deficiency and diagnostic delay.
AB  - AIMS: To assess the occurrence of diagnostic delay in primary antibody deficiency
      in the period 1989-2002, since a similar study in 1989, and to assess the impact
      of UK national guidelines communicated in 1995. METHODS: A retrospective case
      note review was performed of 89 consecutive patients with antibody deficiency
      referred to a regional referral centre for clinical immunology in north west
      England and north Wales. The delay in diagnosis and the estimated resulting
      morbidity in terms of infections were assessed. RESULTS: Fifty six of the 89
      patients experienced delay in diagnosis. The overall median delay was 2 years
      (mean, 4.4), resulting in substantial morbidity (equivalent to two major
      infections and one minor infection). This shows a moderate improvement since the
      previous study in 1989 and since the introduction of UK national guidelines in
      1995. Respiratory infections are the most frequent presenting infections, and
      respiratory physicians the most common source of referral. CONCLUSIONS: There is
      still considerable delay in the diagnosis of primary antibody deficiency, but the
      data suggest an improvement in practice since the previous study in 1989 and the
      distribution of national guidelines in 1995.

PMID- 15858131
TI  - Postmortem molecular diagnosis of sickle beta thalassaemia.
AB  - This report describes a case in which the diagnosis of sickle cell disease (SCD)
      was established after death. The diagnosis of sickle cell syndrome was made in a
      68 year old black patient who was found to have sickled red blood cells in many
      organs at necropsy although the disease had not been diagnosed during her
      lifetime. DNA was isolated from a peripheral blood smear obtained on the day of
      the patient's death. The beta globin gene was polymerase chain reaction amplified
      and sequenced, revealing that the patient had S-beta(+) thalassaemia. This study
      shows that blood smears are a suitable source for retrospective DNA analysis
      studies. This case illustrates that relatively "mild" forms of SCD can be
      overlooked, despite symptomatology suggestive of a sickle syndrome, and
      demonstrates the feasibility of the postmortem molecular diagnosis of
      haemoglobinopathies in such cases.

PMID- 15858132
TI  - Angiocentric immunoproliferative lesion and angiocentric lymphoma of lymph node
      in children. A report of two cases.
AB  - AIM: To report two examples of an angiocentric immunoproliferative lesion (AIL)
      and angiocentric angiodestructive lymphoma (AL) presenting in lymph nodes in
      children. Most commonly involving extranodal sites, AIL/AL rarely presents in the
      spleen and lymph nodes. METHODS/RESULTS: Case 1 presented as a cervical
      lymphadenopathy in a 3 year old girl being treated for pre-B cell acute
      lymphoblastic leukaemia. Histological and immunohistochemistry studies revealed
      an Epstein-Barr virus positive (EBV+), large B cell (CD20 and CD30+) AIL with
      large areas of necrosis, the whole resembling lymphomatoid granulomatosis. Case 2
      presented as a large supraclavicular lymphadenopathy in a 13 year old boy.
      Histology and immunohistochemistry revealed an EBV-, large T cell (CD45RO, CD56,
      and CD30+) AL, presenting the features of so called angiocentric T cell/natural
      killer cell lymphoma, nasal type. CONCLUSIONS: The term AIL/AL refers to a
      heterogeneous group of conditions not unique to a particular type of lymphoid
      cell. These lesions are easily recognised by the histopathologist because of
      their extremely unusual angiocentric pattern. Although rare, AIL/AL may present
      as nodal lesions in children ab initio.

PMID- 15858133
TI  - 5-Fluorouracil/irinotecan induced lethal toxicity as a result of a combined
      pharmacogenetic syndrome: report of a case.
AB  - Combination cancer chemotherapy induced toxicity can be associated with combined
      pharmacogenetic syndromes. Dihydropyrimidine dehydrogenase (DPD) is the principal
      enzyme involved in the catabolic detoxification of 5-fluorouracil (5FU). A
      heterozygous G > A transition at the 5' splicing donor consensus sequence in
      intron 14 leading to exon 14 skipping (IVS14+1 G > A, DPYD*2A) with partial loss
      of enzyme activity may be partly responsible for 5FU induced toxicity, whereas
      irinotecan associated toxicity may in part be explained by an aberrant UGT1A1
      promoter (TA)(n) genotype underlying Gilbert's syndrome with reduced liver
      glucuronidation activity. This report describes a 44 year old white woman who
      suffered from severe gastrointestinal and haematological toxicity while
      undergoing 5FU(24h)/folinic acid/irinotecan treatment for adenocarcinoma of the
      sigmoid colon. Despite appropriate supportive treatment, her condition rapidly
      deteriorated and led to death. Molecular analysis revealed a hitherto undescribed
      combined pharmacogenetic syndrome, consisting of heterozygosity for the DPD
      IVS14+1 G > A mutation and UGT1A1 (TA)(6/7) heterozygosity, which probably
      contributed to the fatal outcome in this patient.

PMID- 15858134
TI  - Implications of increased haemoglobin A2 values in HIV positive women in the
      antenatal clinic.
AB  - Universal antenatal haemoglobinopathy screening in this hospital has identified
      several women with increased haemoglobin A(2) values, but without hypochromic
      microcytic red cell indices. This report describes two cases where there is
      evidence that the raised haemoglobin A(2) value is not caused by heterozygous
      beta thalassaemia, but rather results from these patients being human
      immunodeficiency virus (HIV) positive and on antiretroviral therapy. This will
      have important implications as universal antenatal haemoglobinopathy screening
      becomes more widespread, and as the number of HIV positive women of childbearing
      age increases.

PMID- 15858135
TI  - Know the whole history.

PMID- 15858136
TI  - A case of Aspergillus fumigatus peritonitis in a patient undergoing continuous
      ambulatory peritoneal dialysis (CAPD): diagnostic and therapeutic challenges.

PMID- 15858137
TI  - Immunohistochemical validation of expression microarray results.

PMID- 15858138
TI  - Molecular typing of West Nile Virus, Dengue, and St. Louis encephalitis using
      multiplex sequencing.
AB  - We report the development of an assay to simultaneously identify three of the
      clinically important flaviviruses (West Nile Virus, Dengue, and St. Louis
      encephalitis). This assay is based on the nucleotide sequence variations within a
      266-bp region of the non-structural protein 5. Further, based on the nucleotide
      variations in the same region of the non-structural protein 5, four of the
      present Dengue serotypes were identified. To identify some of the subtypes of WNV
      we have developed a second assay using multiplex sequencing technology. The
      format of the result of this assay is an electropherogram of two genomic segments
      of the WNV genome: a 48-nucleotide sequence from the anchored core protein C and
      a 45-nucleotide sequence coding for the non-structural proteins (proteinase and
      putative helicase genes).

PMID- 15858139
TI  - Microsatellite analysis of hereditary nonpolyposis colorectal cancer-associated
      colorectal adenomas by laser-assisted microdissection: correlation with mismatch
      repair protein expression provides new insights in early steps of tumorigenesis.
AB  - Although microsatellite instability (MSI) testing is a useful tool for molecular
      screening of hereditary nonpolyposis colorectal cancer (HNPCC) carcinomas,
      conflicting results have been obtained in colorectal adenomas. This might result
      from different techniques of tissue sampling and MSI analysis. Alternatively,
      some HNPCC-associated adenomas may follow a molecular route that differs from the
      MSI pathway. In the present study we examined the MSI status of 18 adenomas from
      17 HNPCC patients by comparing manual adenoma dissection under gross visual
      control with laser microdissection of single adenoma crypts. After manual gross
      dissection, 50% (9 of 18) and 11.1% (2 of 18) of the adenomas displayed high
      level (MSI-H) and low-level (MSI-L) MSI, respectively. The same set of adenomas
      split into 83.3% (15 of 18) MSI-H and 5.6% (1 of 18) MSI-L after laser
      microdissection. The expression pattern of mismatch repair (MMR) proteins showed
      a higher concordance rate with the MSI status in laser-dissected (94%) than gross
      dissected (47%) adenomas. Whereas two adenomas remained microsatellite stable
      (MSS) and MMR proficient even after laser-assisted dissection, two MSI-H cases
      showed either rare instabilities at coding microsatellites or intratumoral
      heterogeneity of MSI with and without MSH2 expression. This suggests that in some
      adenomas development of MMR dysfunction occurs stepwise with MSI, arising before
      complete loss of MMR gene expression, whereas other HNPCC-associated adenomas
      might develop independently of MMR deficiency.

PMID- 15858140
TI  - Amplification of whole tumor genomes and gene-by-gene mapping of genomic
      aberrations from limited sources of fresh-frozen and paraffin-embedded DNA.
AB  - Sufficient quantity of genomic DNA can be a bottleneck in genome-wide analysis of
      clinical tissue samples. DNA polymerase Phi29 can be used for the random-primed
      amplification of whole genomes, although the amplification may introduce bias in
      gene dosage. We have performed a detailed investigation of this technique in
      archival fresh-frozen and formalin-fixed/paraffin-embedded tumor DNA by using
      cDNA microarray-based comparative genomic hybridization. Phi29 amplified DNA from
      matched pairs of fresh-frozen and formalin-fixed/paraffin-embedded tumor samples
      with similar efficiency. The distortion in gene dosage representation in the
      amplified DNA was nonrandom and reproducibly involved distinct genomic loci.
      Regional amplification efficiency was significantly linked to regional GC content
      of the template genome. The biased gene representation in amplified tumor DNA
      could be effectively normalized by using amplified reference DNA. Our data
      suggest that genome-wide gene dosage alterations in clinical tumor samples can be
      reliably assessed from a few hundred tumor cells. Therefore, this amplification
      method should lend itself to high-throughput genetic analyses of limited sources
      of tumor, such as fine-needle biopsies, laser-microdissected tissue, and small
      paraffin-embedded specimens.

PMID- 15858141
TI  - Long polymerase chain reaction-based fluorescence in situ hybridization analysis
      of female carriers of X-linked chronic granulomatous disease deletions.
AB  - Chronic granulomatous disease (CGD) is a rare inherited disorder in which
      antimicrobial activity of phagocytes is impaired due to the lack of reactive
      oxygen species, or oxidative burst, produced by NADPH oxidase. The X-linked form
      of CGD, representing approximately 70% of all cases, is caused by mutations in
      the cytochrome b beta subunit (CYBB) gene, which maps to chromosome Xp21.1. CYBB
      encodes the gp91-phox protein, a necessary component in the NADPH oxidase
      pathway. A wide variety of mutations have been identified in X-linked CGD
      patients, all of which lead to deletion of the functional protein and no
      oxidative burst activity. The mutations vary from single nucleotide substitutions
      to deletions of the entire gene. In this article, we report a mutation detection
      method for probands of female relatives at risk for carrier status of large
      deletions of the CYBB gene. Through fluorescent in situ hybridization of
      metaphase chromosomes, we were able to consistently distinguish carriers from
      noncarriers using polymerase chain reaction-derived, labeled DNA specific for
      exons 2 to 13 of the CYBB region at Xp21.1.

PMID- 15858142
TI  - Quantification of SSX mRNA expression in human bone and soft tissue tumors using
      nucleic acid sequence-based amplification.
AB  - The SSX family proteins have been considered new members of the cancer/testis
      antigens because of the restricted expression in testis among normal tissues and
      the activation in a wide range of cancers. Thus, they would be potential
      molecular targets for immunotherapeutic strategies. We have developed a
      competitive nucleic acid sequence-based amplification (NASBA) assay to analyze
      SSX mRNA expression in 211 bone and soft tissue tumors. The copy numbers of SSX
      mRNA per mug of total RNA in tumor tissues were widely distributed, ranging
      logarithmically from 0.6 to 6.6. We found that malignant tumors showed
      significantly higher expression of SSX mRNA than benign tumors (P < 0.0001).
      Further, SSX mRNA expression in stage III tumors was significantly higher than
      that in stage I or II tumors (P < 0.005). This NASBA assay was also more
      sensitive compared to immunohistochemistry using newly affinity-purified
      polyclonal antibody against SSX. Collectively, these results suggest that the SSX
      quantitative NASBA assay could provide useful information to select eligible
      patients for SSX-specific cancer vaccines.

PMID- 15858143
TI  - Type-specific multiple sequencing primers: a novel strategy for reliable and
      rapid genotyping of human papillomaviruses by pyrosequencing technology.
AB  - DNA sequencing is the gold standard method for accurate microbial and viral
      typing. However, DNA sequencing techniques have been facing limitations in typing
      of human papillomaviruses when the specimen harbors multiple genotypes and yields
      nonspecific amplification products, resulting in nonspecific and noninterpretable
      sequence data. To address these limitations we have developed a type-specific
      multiple sequencing primer DNA-sequencing method. This new strategy is suitable
      for sequencing and typing of samples harboring different genotypes (co-infections
      with multiple genotypes) and yielding nonspecific amplifications, thus
      eliminating the need for nested polymerase chain reaction (PCR), stringent PCR
      conditions, and cloning. The new approach has also proved useful for amplicons
      containing low PCR yield or subdominant types, avoiding reperforming of
      amplifications. We have applied the multiple sequencing primer method for
      genotyping of clinically relevant human papillomaviruses in a clinical test panel
      by using a combined pool of seven type-specific sequencing primers for HPV-6, 
      11, -16, -18, -31, -33, and -45. Furthermore, we introduced a sequence pattern
      recognition approach when there was a plurality of genotypes in the sample to
      facilitate typing of more than one target DNA in the sample. The multiple
      sequencing primer method has proved to be a multifaceted approach for typing of
      human papillomaviruses by DNA sequencing technologies.

PMID- 15858145
TI  - Topographic and quantitative display of integrated human immunodeficiency virus-1
      provirus DNA in human lymph nodes by real-time polymerase chain reaction.
AB  - In situ polymerase chain reaction (isPCR) has been applied in many fields that
      require detection of a genomic marker in combination with its topographic
      localization in tissue. We describe here a novel approach that circumvents the
      major drawbacks of in situ PCR, ie, low sensitivity, leakage of DNA from cells,
      and inability to quantify the DNA input. Frozen sections of a lymph node from a
      human immunodeficiency virus (HIV)-1-infected patient were fixed on glass
      microscope slides, and the glass was scored into square fragments of 0.5-mm edge
      length using a diamond cutting device. Slides were then attached to adhesive,
      elastic plastic foil and finally broken, and the foil was extended to allow
      sorting of fragments into PCR microtiter plates. The material was tested for HIV
      1 proviral DNA by a sensitive real-time PCR protocol. Subjacent sections were
      stained for follicular dendritic cells to identify follicles. The fragmentation
      process prevented leakage of amplified DNA to neighboring areas as often
      experienced with in situ PCR. Provirus was clearly associated with follicular
      areas, in which provirus-carrying cells represented an average of 0.8% of the
      total cell population (peak density, 3.1% of all follicular cells). The results
      of this method suggest that the high density of provirus-containing cells in
      follicles may be important for the persistence of proviral DNA in infected
      persons.

PMID- 15858144
TI  - Molecular classification of renal tumors by gene expression profiling.
AB  - Renal tumor classification is important because histopathological subtypes are
      associated with distinct clinical behavior. However, diagnosis is difficult
      because tumor subtypes have overlapping microscopic characteristics. Therefore,
      ancillary methods are needed to optimize classification. We used oligonucleotide
      microarrays to analyze 31 adult renal tumors, including clear cell renal cell
      carcinoma (RCC), papillary RCC, chromophobe RCC, oncocytoma, and angiomyolipoma.
      Expression profiles correlated with histopathology; unsupervised algorithms
      clustered 30 of 31 tumors according to appropriate diagnostic subtypes while
      supervised analyses identified significant, subtype-specific expression markers.
      Clear cell RCC overexpressed proximal nephron, angiogenic, and immune response
      genes, chromophobe RCC oncocytoma overexpressed distal nephron and oxidative
      phosphorylation genes, papillary RCC overexpressed serine protease inhibitors,
      and extracellular matrix products, and angiomyolipoma overexpressed muscle
      developmental, lipid biosynthetic, melanocytic, and distinct angiogenic factors.
      Quantitative reverse transcriptase-polymerase chain reaction and
      immunohistochemistry of formalin-fixed renal tumors confirmed overexpression of
      proximal nephron markers (megalin/low-density lipoprotein-related protein 2,
      alpha-methylacyl CoA racemase) in clear cell and papillary RCC and distal nephron
      markers (beta-defensin 1, claudin 7) in chromophobe RCC/oncocytoma. In summary,
      renal tumor subtypes were classified by distinct gene expression profiles,
      illustrating tumor pathobiology and translating into novel molecular bioassays
      using fixed tissue.

PMID- 15858146
TI  - Analysis of hMLH1 and hMSH2 gene dosage alterations in hereditary nonpolyposis
      colorectal cancer patients by novel methods.
AB  - A significant fraction of hereditary nonpolyposis colorectal cancer cases with
      defective mismatch repair (ie, Lynch syndrome) have large genomic deletions or
      duplications in the mismatch repair genes, hMLH1 and hMSH2, which can be
      challenging to detect by traditional methods. For this study, we developed and
      validated a novel Southern blot analysis method that allows for ascertainment of
      the extent of the dosage alterations on an exon-by-exon basis and compared this
      method to a second novel technique, multiplex ligation-dependent probe
      amplification (MLPA). From a total of 254 patients referred for Lynch syndrome
      testing, 20 of the 118 MLH1 cases and 42 of the 136 MSH2 cases had large genomic
      alterations, as detected by Southern blot. MLPA and Southern blot results were
      concordant with the exception of three major discrepancies: one because of a lack
      of MLPA probes for the region altered, another because of a point mutation near
      the MLPA probe ligation site, and another that was unexplained. Compared to
      Southern blot, MLPA has a shorter turn-around time, the analysis is less costly,
      less time-consuming, and less labor-intensive, and results are generally clear
      and unambiguous. However, concerns with MLPA include the presence of false
      negatives and -positives because of positioning of probes and DNA variants near
      the probe ligation site. Overall, both Southern blot and MLPA provide important
      tools for the complete evaluation of patients with Lynch syndrome.

PMID- 15858147
TI  - Validation and clinical application of a locus-specific polymerase chain reaction
      and minisequencing-based assay for congenital adrenal hyperplasia (21
      hydroxylase deficiency).
AB  - Congenital adrenal hyperplasia is an autosomal recessive disorder caused by
      defective adrenal steroid biosynthesis, resulting in reduced glucocorticoid and
      increased androgen production. The majority of cases are due to inactivation of
      the 21-hydroxylase gene (CYP21A2), most commonly caused by genomic rearrangements
      with the adjacent, highly homologous pseudogene CYP21A. The most common deletions
      and gene conversion events have been defined and are typically detected by
      Southern hybridization detection of CYP21 rearrangements and/or polymerase chain
      reaction (PCR). However, Southern hybridization is laborious, and allele-specific
      PCR results may be difficult to interpret. We have therefore developed a locus
      specific, PCR-based, minisequencing method for detecting the 12 most common
      CYP21A2 mutations. We validated the assay using a panel of 20 previously
      genotyped samples obtained from individuals who collectively have a broad
      spectrum of mutations causing 21-hydroxylase deficiency. We also used 19 control
      samples having no CYP21 mutations. All validation samples were correctly typed,
      and we identified haplotypes that may be useful for clinical diagnosis. Results
      from 102 clinical samples demonstrate that this assay is a rapid, reliable, and
      robust method for locus-specific identification of mutations and is suitable for
      routine clinical use and prenatal diagnosis.

PMID- 15858148
TI  - A novel method for creating artificial mutant samples for performance evaluation
      and quality control in clinical molecular genetics.
AB  - The lack of readily available, patient-derived materials for molecular genetic
      testing of many heterozygous or rare disorders creates a major impediment for
      laboratory proficiency and quality control procedures. The paucity of clinically
      derived mutation-positive samples could be surmounted if it were possible to
      construct artificial samples containing mutations of interest that would
      sufficiently resemble natural human samples. Such samples could then function as
      acceptable and realistic performance evaluation challenges and quality control
      reagents for recipient laboratories. Using the cystic fibrosis gene (CFTR) as a
      prototype, we have devised and executed experiments designed to generate unique
      DNA samples that could be used for these purposes. We used site-directed
      mutagenesis to generate mutations of interest in plasmid DNA derived from common
      bacterial artificial chromosome sources containing the cystic fibrosis
      transmembrane conductance receptor gene. CFTR mutations G85E and 1078delT were
      chosen to represent mutations in the original American College of Medical
      Genetics-recommended population-screening panel of 25 mutations. DNA samples
      containing predetermined concentrations and ratios of wild-type and mutated
      plasmids, bacterial artificial chromosomes of interest, and nonhuman genomic
      carrier DNA were characterized and tested in-house and in a group of nine pilot
      testing laboratories using a variety of technical platforms. The results indicate
      that these constructs, containing CFTR mutations in heterozygous and homozygous
      states, can serve as valid and accessible materials for quality assurance,
      including performance evaluation, proficiency testing, and assay quality control.

PMID- 15858149
TI  - c-kit Mutations in patients with childhood-onset mastocytosis and genotype
      phenotype correlation.
AB  - Mastocytosis represents a clonal proliferation of mast cell hematopoietic
      progenitors caused by gain-of-function mutations of the c-kit gene. The
      heterogeneity of c-kit mutations may have contributed to difficulties in
      characterizing genotype-phenotype correlation of the disease. Our goal was to
      analyze a set of reported pathogenic c-kit mutations in patients with childhood
      onset cutaneous mastocytosis, in comparison with those with adult-onset disease,
      and to correlate these with clinical presentation. We performed polymerase chain
      reaction and direct sequencing using genomic DNA samples from 16 nonfamilial
      Japanese patients with indolent cutaneous mastocytosis (12 with childhood-onset
      disease and 4 with adult-onset disease) to look for the most common c-kit
      mutations at codons 816, 560, 820, and 839. A substantial number of patients had
      missense codon 816 mutations (10 of 12 in the childhood-onset group, 83.3%; and 4
      of 4 in the adult-onset group, 100%). The most common mutation was Asp816Val (9
      of 16, 64.3%) followed by Asp816Phe (5 of 16, 35.7%). Moreover, children with the
      Asp816Phe mutation developed cutaneous mastocytosis at an earlier age as compared
      to those with the Asp816Val mutation (mean age of onset, 1.3 months versus 5.9
      months, respectively; P = 0.068). No other mutation variations were found in our
      cohort. In summary, we confirmed a high incidence of two distinct c-kit
      mutations, Asp816Val and Asp816Phe, in patients with childhood-onset cutaneous
      mastocytosis. Our results provide new insights into common c-kit mutations, which
      may contribute to different clinical courses of the disease.

PMID- 15858150
TI  - Mitochondrial DNA as a cancer biomarker.
AB  - As part of a national effort to identify biomarkers for the early detection of
      cancer, we developed a rapid and high-throughput sequencing protocol for the
      detection of sequence variants in mitochondrial DNA. Here, we describe the
      development and implementation of this protocol for clinical samples.
      Heteroplasmic and homoplasmic sequence variants occur in the mitochondrial genome
      in patient tumors. We identified these changes by sequencing mitochondrial DNA
      obtained from tumors and blood from the same individual. We confirmed previously
      identified primary lung tumor changes and extended these findings in a small
      patient cohort. Eight sequence variants were identified in stage I to stage IV
      tumor samples. Two of the sequence variants identified (22%) were found in the D
      loop region, which accounts for 6.8% of the mitochondrial genome. The other
      sequence variants were distributed throughout the coding region. In the forensic
      community, the sequence variations used for identification are localized to the D
      loop region because this region appears to have a higher rate of mutation.
      However, in lung tumors the majority of sequence variation occurred in the coding
      region. Hence, incomplete mitochondrial genome sequencing, designed to scan
      discrete portions of the genome, misses potentially important sequence variants
      associated with cancer or other diseases.

PMID- 15858151
TI  - A novel semiquantitative fluorescence-based multiplex polymerase chain reaction
      assay for rapid simultaneous detection of bacterial and parasitic pathogens from
      blood.
AB  - A multiplex polymerase chain reaction assay was developed for the rapid
      simultaneous detection of category A select bacterial agents (Bacillus anthracis
      and Yersinia pestis) and parasitic pathogens (Leishmania species) in blood using
      the Cepheid Smart Cycler platform. B. anthracis (Sterne) and Yersinia.
      pseudotuberculosis were used in the assay for optimization for B. anthracis and
      Y. pestis, respectively. The specificity of the target amplicons [protective
      antigen gene of B. anthracis and rRNA genes of other pathogens or human (internal
      control)] was evaluated by staining the amplicons with SYBR Green I and
      determining their individual melting temperatures (T(m)). As a novel approach for
      pathogen semiquantitation, the Tm peak height of the amplicon was correlated with
      a known standard curve of pathogen-spiked samples. This assay was able to detect
      DNA in blood spiked with less than 50 target cells/ml for all of the pathogens.
      The sensitivity of this assay in blood was 100% for the detection of Leishmania
      donovani from leishmaniasis patients and B. anthracis (Sterne) from symptomatic
      mice. The time necessary for performing this assay including sample preparation
      was less than 1.5 hours, making this a potentially useful method for rapidly
      diagnosing and monitoring the efficacy of drugs or vaccines in infected
      individuals.

PMID- 15858152
TI  - Statistical considerations for immunohistochemistry panel development after gene
      expression profiling of human cancers.
AB  - In recent years there have been a number of microarray expression studies in
      which different types of tumors were classified by identifying a panel of
      differentially expressed genes. Immunohistochemistry is a practical and robust
      method for extending gene expression data to common pathological specimens with
      the advantage of being applicable to paraffin-embedded tissues. However, the
      number of assays required for successful immunohistochemical classification
      remains unclear. We propose a simulation-based method for assessing sample size
      for an immunohistochemistry investigation after a promising gene expression study
      of human tumors. The goals of such an immunohistochemistry study would be to
      develop and validate a marker panel that yields improved prognostic
      classification of cancer patients. We demonstrate how the preliminary gene
      expression data, coupled with certain realistic assumptions, can be used to
      estimate the number of immunohistochemical assays required for development. These
      assumptions are more tenable than alternative assumptions that would be required
      for crude analytic sample size calculations and that may yield underpowered and
      inefficient studies. We applied our methods to the design of an
      immunohistochemistry study for glioma classification and estimated the number of
      assays required to ensure satisfactory technical and prognostic validation.
      Simulation approaches for computing power and sample size that are based on
      existing gene expression data provide a powerful tool for efficient design of
      follow-up genomic studies.

PMID- 15858153
TI  - Nine novel germline gene variants in the RET proto-oncogene identified in twelve
      unrelated cases.
AB  - We report nine novel DNA alterations in the RET proto-oncogene in 12 unrelated
      cases identified by DNA sequencing of exons 10 and 11 of the gene. The novel
      variants K666E, IVS9-11G-->A, D631V in cis with H665Q, D631E (with C634Y), E623K
      (in trans with C618S), 616delGAG (in trans with C609Y), Y606C, C630R, and R635
      T636insELCR;T636P were detected in patients with various clinical presentations
      ranging from thyroid goiter, medullary thyroid carcinoma, and pheochromocytoma to
      classic multiple endocrine neoplasia type 2A. When novel DNA alterations are
      found, extended family studies can be helpful in determining the clinical
      significance of such findings. Segregation within families suggests that K666E
      and T636insELCR;T636P are likely to be disease-causing mutations. However, the
      mechanism by which they affect the normal activity of the RET receptor is
      unclear. Absence of segregation with disease was observed for E623K and
      616delGAG. For the remainder of the DNA alterations, family studies were not
      possible, and the clinical significance of these novel variants needs further
      assessment. Additional case reports, animal models, and/or functional studies are
      needed to determine the clinical significance of these newly identified variants.

PMID- 15858154
TI  - Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics:
      novel mutations and assessment of a population-specific mutation spectrum.
AB  - Characterization of CFTR mutations in the U.S. Hispanic population is vital to
      early diagnosis, genetic counseling, patient-specific treatment, and the
      understanding of cystic fibrosis (CF) pathogenesis. The mutation spectrum in
      Hispanics, however, remains poorly defined. A group of 257 self-identified
      Hispanics with clinical manifestations consistent with CF were studied by
      temporal temperature gradient electrophoresis and/or DNA sequencing. A total of
      183 mutations were identified, including 14 different amino acid-changing novel
      variants. A significant proportion (78/85) of the different mutations identified
      would not have been detected by the ACMG/ACOG-recommended 25-mutation screening
      panel. Over one third of the mutations (27/85) occurred with a relative frequency
      >1%, which illustrates that the identified mutations are not all rare. This is
      supported by a comparison with other large CFTR studies. These results underscore
      the disparity in mutation identification between Caucasians and Hispanics and
      show utility for comprehensive diagnostic CFTR mutation analysis in this
      population.

PMID- 15858155
TI  - B-cell clonality determination using an immunoglobulin kappa light chain
      polymerase chain reaction method.
AB  - To augment the detection of clonality in B-cell malignancies, we designed a
      consensus primer kappa light chain gene (Igkappa) polymerase chain reaction (PCR)
      assay in combination with a consensus primer immunoglobulin heavy chain gene
      (IgH) PCR assay. Its efficacy was then evaluated in a series of 86 paraffin
      tissue samples comprising neoplastic and reactive lymphoproliferations. Analysis
      after PCR was accomplished by 10% native polyacrylamide gel electrophoresis after
      heteroduplex pretreatment of PCR products and by a post-PCR chip-based capillary
      electrophoresis analytic method. Overall, 49 of 68 (72%) of mature B-cell
      neoplasms yielded discrete Igkappa gel bands within the predicted size range with
      no clonotypic Igkappa products observed among reactive lymphoid or T-cell
      proliferations. The application of Igkappa PCR improved overall sensitivity from
      81% with IgH PCR alone to 90% with combined Igkappa/IgH PCR, with this effect
      being most notable in germinal center-related lymphomas. Sequencing of positive
      Igkappa rearrangements revealed that most rearrangements involved members of the
      Vkappa1 (40%) and Vkappa2 (34%) gene families along with Jkappa1 (26%), Jkappa2
      (23%), and Jkappa4 (51%) gene segments. Involvement of Vkappa pseudogenes was
      identified in 24% of cases with Vkappa-KDE rearrangements. Our results
      demonstrate the efficacy of Igkappa PCR in improving the detection rate of
      clonality in B-cell neoplasms and further introduce a novel post-PCR chip-based
      capillary electrophoresis analytic method for rapid PCR fragment size evaluation.

PMID- 15858156
TI  - Multiplex detection of Ehrlichia and Anaplasma species pathogens in peripheral
      blood by real-time reverse transcriptase-polymerase chain reaction.
AB  - Tick-borne infections are responsible for many emerging diseases in humans and
      several vertebrates. These include human infections with Anaplasma
      phagocytophilum, Ehrlichia chaffeensis, and Ehrlichia ewingii. Because single or
      co-infections can result from tick bites, the availability of a rapid, multiplex
      molecular test will be valuable for timely diagnosis and treatment. Here, we
      describe a multiplex molecular test that can detect single or co-infections with
      up to five Ehrlichia and Anaplasma species. The test protocol includes the
      magnetic capture-based purification of 16S ribosomal RNA, its enrichment, and
      specific-pathogen(s) detection by real-time reverse transcriptase-polymerase
      chain reaction. We also report a unique cloning strategy to develop positive
      controls in the absence of a pathogen's genomic DNA. The test was assessed by
      examining blood samples from dogs suspected to be positive for ehrlichiosis. The
      dog was chosen as the model system because it is susceptible to acquire
      infections with up to five pathogens of the genera Ehrlichia and Anaplasma. The
      test identified single infections in the canine host with E. chaffeensis, E.
      canis, E. ewingii, A. phagocytophilum, and A. platys and co-infection with E.
      canis and A. platys. The multipathogen detection and novel positive control
      development procedures described here will be valuable in monitoring infections
      in people, other vertebrates, and ticks.

PMID- 15858157
TI  - Tyrosinase and tyrosinase related protein 1 alleles specify domestic cat coat
      color phenotypes of the albino and brown loci.
AB  - The genes encoding enzymes of the tyrosinase family are strong candidates for
      coat color variation in mammals. To investigate their influence in domestic cat
      coat color, we determined the complete nucleotide coding sequence of the domestic
      cat genes tyrosinase (TYR)--a plausible candidate gene for the albino (C) locus,
      and tyrosinase related protein 1 (TYRP1)--a candidate gene for the brown (B)
      locus. Sequence variants between individuals exhibiting variation in pigmentation
      were submitted to association studies. In TYR, two nonsynonymous substitutions
      encoding TYR-G301R and TYR-G227W were associated with the siamese and burmese
      phenotypes of the albino locus, respectively. TYRP1 was mapped on chromosome D4
      within 5 cM of a highly polymorphic microsatellite, previously found to be fixed
      in a cat breed selected for the chocolate (b) allele of the B locus, which
      reinforced TYRP1 as a candidate gene for the B locus in the domestic cat. Two DNA
      polymorphisms, one leading to a TYRP1-A3G substitution in the signal peptide and
      another to an in-frame insertion TYRP1-421ins17/18 caused by a donor splice site
      mutation in intron 6, were associated with the chocolate (b) allele. A premature
      UAG stop codon at position 100 of TYRP1 was associated with a second allele of
      the B locus, cinnamon (b(l)). The results provide very strong evidence that the
      specific nucleotide variants of feline TYR (chromosome D1) are causative of the
      siamese (c(s)) and burmese (c(b)) alleles of the albino locus, as well as
      nucleotide variants of TYRP1 (chromosome D4) as specifying the chocolate (b) and
      cinnamon (b(l)) alleles of the B locus.

PMID- 15858158
TI  - Genome size evolution in New Zealand triplefin fishes.
AB  - The genome sizes of 18 species of New Zealand triplefin fishes (family
      Tripterygiidae) were determined by flow cytometry of erythrocytes. The
      evolutionary relationships of these species were examined with a molecular
      phylogeny derived from DNA sequence data based on 1771 base pairs from fragments
      of three mitochondrial loci (12S and 16S ribosomal RNA, and the control region)
      and one nuclear locus (ETS2). Haploid genome sizes ranged from .85 pg (1C) to
      1.28 pg with a mean of 1.15 +/- .01pg. Genome size appeared to be highly plastic,
      with up to 20% variation occurring within genera and a 50% difference in size
      between the smallest and the largest genome. No evidence was found to indicate
      polyploidy as a mechanism for speciation in New Zealand triplefins. Factors
      suggested to influence genome sizes of other organisms, such as morphological
      complexity, neoteny, and longevity, do not appear to be associated with shifts in
      the genome sizes of New Zealand triplefins.

PMID- 15858159
TI  - Motor cortex dynamics in visuomotor production of speech and non-speech mouth
      movements.
AB  - We investigated timing and hemispheric balance of motor cortex activation when
      kinetically similar speech and non-speech mouth movements and sequences of such
      movements were triggered by visually presented letter- and symbol-strings. As an
      index of motor cortex activation, we used magnetoencephalographic recording of
      task-related change of precentral 20 Hz (16-24 Hz) activity. Suppression of the
      20 Hz rhythm revealed pre-movement activation in the face representation areas
      that was tied to visual instruction, not movement onset. The 20 Hz rhythm
      remained suppressed throughout the preparation and execution of mouth movements
      and was followed by post-movement rebound. Left hemisphere preceded the right at
      the onset and offset of the suppression, similarly for isolated and sequential
      speech and non-speech movements. Pattern of task-related change in 20 Hz activity
      was otherwise symmetrical. In the face areas, the overall modulation of 20 Hz
      activity increased with sequence length and motor demands. Hand representation
      areas showed also weak reactivity, with systematically larger modulation of 20 Hz
      activity for non-speech than speech movements. Our results suggest an active role
      for the motor cortex in cognitive control of visually triggered mouth movements,
      not limited to movement execution.

PMID- 15858160
TI  - Dissociable roles of prefrontal and anterior cingulate cortices in deception.
AB  - Recent neuroimaging studies have shown the importance of the prefrontal and
      anterior cingulate cortices in deception. However, little is known about the role
      of each of these regions during deception. Using positron emission tomography
      (PET), we measured brain activation while participants told truths or lies about
      two types of real-world events: experienced and unexperienced. The imaging data
      revealed that activity of the dorsolateral, ventrolateral and medial prefrontal
      cortices was commonly associated with both types of deception (pretending to know
      and pretending not to know), whereas activity of the anterior cingulate cortex
      (ACC) was only associated with pretending not to know. Regional cerebral blood
      flow (rCBF) increase in the ACC was positively correlated with that in the
      dorsolateral prefrontal cortex only during pretending not to know. These results
      suggest that the lateral and medial prefrontal cortices have general roles in
      deception, whereas the ACC contributes specifically to pretending not to know.

PMID- 15858161
TI  - Behavioral deficits and cortical damage loci in cerebral achromatopsia.
AB  - Lesions to ventral occipital cortex can produce severe deficits in color vision,
      a syndrome known as cerebral achromatopsia. Because most studies examine
      relatively few cases, however, uncertainty remains about precisely which cortical
      loci, when damaged, produce the syndrome. In addition, the extents of the
      associated perceptual deficits remain unclear. To address these issues, we
      performed a meta-analysis of 92 case reports from the literature. The severity of
      color vision deficits of the cases varied greatly, although nearly all showed
      some deficit in color discrimination. Almost all cases tested also showed some
      loss of spatial vision. Lesion overlap analyses revealed a relatively small
      region of high overlap in ventral occipital cortex. The region of high overlap
      was located near areas identified by neuroimaging studies as important for color
      perception. For comparison, we performed a similar analysis of prosopagnosia, a
      disorder of face perception, and found several regions of high lesion overlap
      adjacent to the region associated with achromatopsia. Because the behavioral
      deficits in achromatopsia are often incomplete and never restricted to color
      vision, the region of high lesion overlap may be one critical stage within a
      stream of many visual areas that participate nonexclusively in color perception.

PMID- 15858162
TI  - My body or yours? The effect of visual perspective on cortical body
      representations.
AB  - A human body part, such as a foot, may be observed from an egocentric perspective
      (consistent with looking at one's own body, e.g. top of the foot, toes pointing
      up) or from an allocentric perspective (only consistent with looking at someone
      else, e.g. top of the foot, toes pointing downwards). We found that the right
      extrastriate body area (EBA) response to images of body parts was enhanced for
      body parts presented from an allocentric perspective. Other areas of extrastriate
      cortex which responded robustly to images of bodies, including the right lateral
      occipital complex, right MT and left EBA, nevertheless did not distinguish
      between the two perspectives. A region of primary somatosensory cortex showed the
      reverse selectivity: the blood oxygen level-dependent response to body parts
      presented from an allocentric perspective was suppressed. These results help to
      illuminate the integration of visual and tactile information by which the brain
      identifies seen body parts as belonging to the self or to another person.

PMID- 15858163
TI  - Functional response properties of neurons in the dorsomedial visual area of New
      World monkeys (Callithrix jacchus).
AB  - The dorsomedial visual area (DM), a subdivision of extrastriate cortex located
      near the dorsal midline, is characterized by heavy myelination and a relative
      emphasis on peripheral vision. To date, DM remains the least understood of the
      three primary targets of projections from the striate cortex (V1) in New World
      monkeys. Here, we characterize the responses of DM neurons in anaesthetized
      marmosets to drifting sine wave gratings. Most (82.4%) cells showed bidirectional
      sensitivity, with only 6.9% being strongly direction selective. The distribution
      of orientation sensitivity was bimodal, with a distinct population (corresponding
      to over half of the sample) formed by neurons with very narrow selectivity. When
      compared with a sample of V1 units representing a comparable range of
      eccentricities, DM cells revealed a preference for much lower spatial
      frequencies, and higher speeds. End inhibition was extremely rare, and the
      responses of many cells summated over distances as large as 30 degrees. Our
      results suggest clear differences between DM and the two other main targets of V1
      projections, the second (V2) and middle temporal (MT) areas, with cells in DM
      emphasizing aspects of visual information that are likely to be relevant for
      motor control.

PMID- 15858164
TI  - Motor control in basal ganglia circuits using fMRI and brain atlas approaches.
AB  - In this study, we examined how the motor, premotor and associative basal ganglia
      territories process movement parameters such as the complexity and the frequency
      of movement. Twelve right-handed volunteers were studied using EPI BOLD contrast
      (3 T) while performing audio-paced finger tapping tasks designed to differentiate
      basal ganglia territories. Tasks varied movement complexity (repetitive index
      tapping, simple sequence of finger movements and complex sequence of 10 moves)
      and frequency (from 0.5 to 3 Hz). Activation maps were coregistered onto a 3-D
      brain atlas derived from post-mortem brains. Three main patterns of activation
      were observed. In the posterior putamen and the sensorimotor cortex, signal
      increased with movement frequency but not with movement complexity. In premotor
      areas, the anterior putamen and the ventral posterolateral thalamus, signal
      increased regularly with increasing movement frequency and complexity. In rostral
      frontal areas, the caudate nucleus, the subthalamic nucleus and the ventral
      anterior/ventrolateral thalamus, signal increased mainly during the complex task
      and the high frequency task (3 Hz). These data show the different roles of motor,
      premotor and associative basal ganglia circuits in the processing of motor
      related operations and suggest that activation can be precisely located within
      the entire circuitry of the basal ganglia.

PMID- 15858165
TI  - Growth of neurites toward neurite- neurite contact sites increases synaptic
      clustering and secretion and is regulated by synaptic activity.
AB  - The integrative properties of dendrites are determined by several factors,
      including their morphology and the spatio-temporal patterning of their synaptic
      inputs. One of the great challenges is to discover the interdependency of these
      two factors and the mechanisms which sculpt dendrites' fine morphological
      details. We found a novel form of neurite growth behavior in neuronal cultures of
      the hippocampus and cortex, when axons and dendrites grew directly toward neurite
      neurite contact sites and crossed them, forming multi-neurite intersections
      (MNIs). MNIs were found at a frequency higher than obtained by computer
      simulations of randomly distributed dendrites, involved many of the dendrites and
      were stable for days. They were formed specifically by neurites originating from
      different neurons and were extremely rare among neurites of individual neurons or
      among astrocytic processes. Axonal terminals were clustered at MNIs and exhibited
      higher synaptophysin content and release capability than in those located
      elsewhere. MNI formation, as well as enhancement of axonal terminal clustering
      and secretion at MNIs, was disrupted by inhibitors of synaptic activity. Thus,
      convergence of axons and dendrites to form MNIs is a non-random activity
      regulated wiring behavior which shapes dendritic trees and affects the location,
      clustering level and strength of their presynaptic inputs.

PMID- 15858166
TI  - An integrate-and-fire model of prefrontal cortex neuronal activity during
      performance of goal-directed decision making.
AB  - The orbital frontal cortex appears to be involved in learning the rules of goal
      directed behavior necessary to perform the correct actions based on perception to
      accomplish different tasks. The activity of orbitofrontal neurons changes
      dependent upon the specific task or goal involved, but the functional role of
      this activity in performance of specific tasks has not been fully determined.
      Here we present a model of prefrontal cortex function using networks of integrate
      and-fire neurons arranged in minicolumns. This network model forms associations
      between representations of sensory input and motor actions, and uses these
      associations to guide goal-directed behavior. The selection of goal-directed
      actions involves convergence of the spread of activity from the goal
      representation with the spread of activity from the current state. This spiking
      network model provides a biological implementation of the action selection
      process used in reinforcement learning theory. The spiking activity shows
      properties similar to recordings of orbitofrontal neurons during task
      performance.

PMID- 15858167
TI  - Constantly updated knowledge of Hsp90.
AB  - Although protein folding, in principle is a spontaneous process which depends
      only upon the amino-acid sequence, the assistance of molecular chaperones is
      required for many proteins to achieve their final conformation in vivo. While
      Hsp90 is one of the major molecular chaperones, it has long been the most
      mysterious among them. Recent advances in our knowledge regarding Hsp90 structure
      and function, owing to both detailed biochemical and genetic characterizations of
      Hsp90 co-chaperones, as well as eminent structural studies have established Hsp90
      as an ATPase-dependent chaperone, and have provided a paradigm of the Hsp90
      chaperone cycle, which is sequentially tuned and coordinated by a variety of co
      chaperones. Here we summarize the current knowledge regarding the structure and
      essential activities of Hsp90, which certainly promises a deeper understanding of
      the functions of Hsp90 in vivo.

PMID- 15858168
TI  - Control of cell fate by Hsp70: more than an evanescent meeting.
AB  - During their lifetime, proteins inevitably expose hydrophobic segments within the
      polypeptide chains on a molecule's surface, which may be otherwise buried inside
      the molecules in the proper conformation. This potentially dangerous situation is
      managed with the aid of the 70-kDa heat shock proteins (Hsp70s) and other
      molecular chaperones. Although a major function of Hsp70 is assisting in
      efficient folding of anonymous proteins in unfolded states, recent studies have
      revealed that Hsp70 plays a variety of specific roles, sometimes deciding the
      cell fate. These multiple activities are based on the specific binding of Hsp70
      to proteins in native states, which regulate cell growth and/or death. It is now
      well recognized that unfolding of some proteins may cause serious diseases,
      especially those associated with neurodegeneration, such as Alzheimer's disease.
      It is suggested that Hsp70 might be a potential drug against these diseases, but
      caution should be taken because Hsp70 exerts multiple effects by binding to
      specific proteins.

PMID- 15858169
TI  - Structural reorganization of the copper binding site involving Thr15 of
      mavicyanin from Cucurbita pepo medullosa (zucchini) upon reduction.
AB  - Mavicyanin, a glycosylated protein isolated from Cucurbita pepo medullosa
      (zucchini), is a member of the phytocyanin subfamily containing one polypeptide
      chain of 109 amino residues and an unusual type-I Cu site in which the copper
      ligands are His45, Cys86, His91, and Gln96. The crystal structures of oxidized
      and reduced mavicyanin were determined at 1.6 and 1.9 A resolution, respectively.
      Mavicyanin has a core structure of seven polypeptide beta-strands arranged as a
      beta-sandwich organized into two beta-sheets, and the structure considerably
      resembles that of stellacyanin from cucumber (CST) or cucumber basic protein
      (CBP). A flexible region was not observed on superimpositioning of the oxidized
      and reduced mavicyanin structures. However, the Cu(II)-epsilon-O-Gln96 bond
      length was extended by 0.47 A, and the Thr15 residue was rotated by 60.0 degrees
      and O-gamma1-Thr15 moved from a distance of 4.78 to 2.58 A from the ligand Gln96
      forming a new hydrogen bond between O-gamma1-Thr15 and epsilon-O-Gln96 upon
      reduction. The reorganization of copper coordination geometry of mavicyanin upon
      reduction arouses reduction potential decreased above pH 8 [Battistuzzi et al.
      (2001) J. Inorg. Biochem. 83, 223-227]. The rotation of Thr15 and the hydrogen
      bonding with the ligand Gln96 may constitute structural evidence of the decrease
      in the reduction potential at high pH.

PMID- 15858170
TI  - Alterations in the extracellular matrix proteoglycan profile in Dupuytren's
      contracture affect the palmar fascia.
AB  - Dupuytren's disease is a palmar fibromatosis associated with changes in
      fibroblast activity that also affect the metabolism of extracellular matrix
      components. In contrast to disease connected alterations in collagen and non
      collagenous glycoproteins (mainly fibronectin), the metabolism of proteoglycans,
      being glycosaminoglycan modified glycoproteins, is poorly understood. Thus, the
      aim of the present study was the characterization of matrix proteoglycans (PGs)
      derived from normal fascia and Dupuytren's fascia. Extracted and purified PGs
      (particularly small PGs) were analysed for content, molecular mass,
      immunoreactivity and glycosaminoglycan chain structure. The matrix of normal
      fascia mainly contains decorin [small dermatan sulfate (DS) PG] with biglycan
      (another small DSPG) and large chondroitin sulfate(CS)/DSPG representing minor
      components. Dupuytren's disease is associated with the remodeling of matrix PG
      composition. The most prominent alteration is an accumulation of biglycan
      frequently bearing DS chains with higher molecular masses. Moreover, the amount
      of large CS/DSPG is increased. In contrast, decorin displays changes affecting
      mainly DS chain structure reflected in (i) an increase in some chain molecular
      masses, (ii) an enhanced content of iduronate disaccharide clusters, and (iii)
      oversulfation of disaccharide repeats. The PG alterations observed in Dupuytren's
      fascia may influence the matrix properties and contribute to disease progression.

PMID- 15858171
TI  - Characterization of recombinant amyloidogenic chicken cystatin mutant I66Q
      expressed in yeast.
AB  - Amyloidogenic chicken cystatin mutant I66Q (cC I66Q) was successfully secreted by
      yeasts Pichia pastoris and Saccharomyces cerevisiae. The soluble monomer and
      dimer forms of amyloidogenic cC I66Q were found in the culture medium, while
      large amounts of insoluble aggregate and polymeric form cC I66Q besides the
      monomer and dimer forms were secreted into the culture medium. The amyloidogenic
      cC I66Q showed a comparable circular dichroism spectrum to that of the wild
      cystatin, and the monomer form exhibited a similar level of inhibitory activity
      toward papain, but the dimmer form did not. During storage of amyloidogenic cC
      I66Q under physiological and acidic conditions, typical binding with Congo red
      and thioflavin T, and the formation of amyloid fibrils were observed, whereas the
      characteristic of similar amyloidosis was hardly detected for the wild
      recombinant cystatin.

PMID- 15858172
TI  - Normal human sera contain bactericidal IgG that binds to the oligosaccharide
      epitope expressed within lipooligosaccharides of Neisseria gonorrhoeae.
AB  - Although more than several investigators reported the presence of antibodies in
      normal human sera (NHS) that bind to lipooligosaccharide (LOS) of Neisseria
      gonorrhoeae, the specificities of those antibodies were not fully characterized.
      To identify anti-LOS antibodies in NHS, we used LOS from a serum-sensitive
      strain, JW31R, as an affinity ligand and purified IgG from NHS that bound to
      JW31R LOS. The affinity purified IgG (AP-IgG) binds to the oligosaccharide (OS)
      moiety of both the ligand LOS and its truncated form, 15253 LOS. Lipid A could be
      essential for maximum expression of the carbohydrate epitope that resides on
      15253 OS. We also found that AP-IgG is capable of killing a serum-sensitive
      strain JW31R. The present work provided direct evidence that NHS contain
      bactericidal antibodies specific for a site close to the inner core OS expressed
      on gonococcal LOS. The present results not only show that anti-LOS antibodies
      specific for the inner core OS could play a major role in our defense against
      gram-negative bacteria. But also they demonstrated that such core OS or a nearby
      site could be utilized as possible targets for vaccine development against
      microbial infections.

PMID- 15858173
TI  - Denervation enhances the expression of SHPS-1 in rat skeletal muscle.
AB  - SHPS-1 (Src homology 2 domain containing protein tyrosine phosphatase substrate
      1) is a transmembrane glycoprotein containing three immunoglobulin-like motifs in
      its extracellular domain and immunoreceptor tyrosine-based inhibitory motifs
      (ITIM) that interact with SHP-2 (Src homology 2 domain containing protein
      tyrosine phosphatase-2) in its cytoplasmic region. SHPS-1 is highly expressed in
      brain, but at much lower levels in skeletal muscle. In this study, we found that
      the level of the SHPS-1 mRNA increases in rat skeletal muscle after denervation.
      Western blot analysis also confirmed the increase of SHPS-1 in denervated muscle.
      Moreover, it was found that the glycosylation of SHPS-1 is N-linked in a muscle
      specific manner, and that this is altered upon innervation or denervation.
      Immunohistochemistry revealed SHPS-1 immunoreactivity at neuromuscular junctions
      (NMJs) under innervation, whereas immunoreactivity was observed extrasynaptically
      in muscle fibers after denervation. Our results indicate that the expression,
      glycosylation, and localization of SHPS-1 are strongly regulated by the nervous
      system, and that SHPS-1 may play an important role in denervated skeletal muscle.

PMID- 15858174
TI  - Prevention of PERV infections in pig to human xenotransplantation by the RNA
      interference silences gene.
AB  - The possibility of preventing the transmission of porcine endogenous retrovirus
      (PERV) to human cells using short interfering RNAs (siRNA) was investigated. The
      siRNA for the p30 of PERV gag region was cloned into pSUPER, the polymerase-III
      H1-RNA gene promoter. A green fluorescence protein (GFP) was also cloned into
      pSUPER to establish pSXGH. Pig endothelial cells (PEC) were transduced with the
      LacZ gene by pseudotype infection, and infected with PERV subtype B, resulting in
      the formation of PEC(LacZ)/PB. The PEC(LacZ)/PB was next transfected with pSXGH
      siRNA. The expression of siRNA was provisionally checked by determining the level
      of expression of GFP. Culture supernatants of infected cells were then inoculated
      into HEK293 cells. The siRNA clearly destroyed the PERV infectivity of
      PEC(LacZ)/PB in both transient cell lines and stable clones. Moreover, the
      decreased levels of mRNA and gag protein were evidenced in the stable clones by
      real-time PCR and Western blotting, respectively. The final goal of our study was
      to establish a transgenic pig expressing the siRNA for PERV. The results suggest
      that siRNA represents a novel approach for controlling PERV infections in
      clinical xenotransplantation.

PMID- 15858175
TI  - Involvement of general transcriptional coactivator PC4 in the transcription of
      medaka fish intestine-specific membrane guanylyl cyclase gene (OlGC6).
AB  - A recent study showed that the AGACCTTTGC nucleotides sequence (between -90 and 
      81) contained in the cis-regulatory element in an intestine-specific membrane
      guanylyl cyclase gene, OlGC6, of the medaka fish, Oryzias latipes, are important
      for the transcription of the gene in mammalian cultured cell line and in medaka
      fish. Using sequence-specific DNA affinity chromatography, we purified a cis
      regulatory element-binding protein from a medaka fish intestinal nuclear extract
      and used mass spectrometry to identify it as a medaka fish homologue of general
      transcriptional coactivator PC4, which we designated as OlPC4. The expression of
      the OlPC4 gene was detected in embryos, as well as in a large variety of tissues
      of adult medaka fish. Using a 17-kDa recombinant OlPC4, we carried out an
      ultraviolet (UV) cross-linking experiment and an electrophoretic mobility shift
      assay (EMSA), and demonstrated that the recombinant OlPC4 can be substituted for
      native OlPC4 in medaka fish intestinal nuclear extracts. In CACO-2 cells,
      cotransfection of the OlGC6-luciferase fusion genes with an OlPC4 expression
      vector resulted in 1.5-fold stimulation of the OlGC6 promoter.

PMID- 15858176
TI  - Alanine-scanning mutagenesis of HM-1 killer toxin and the essential residues for
      killing activity.
AB  - Each of the aromatic, acidic and basic amino acid residues in HM-1 were
      separately substituted with alanine by site-directed mutagenesis. The mutant
      genes were successfully expressed in HM-1 resistant Saccharomyces cerevisiae. HM
      1 gene analogues corresponding to the aromatic substitutions resulted in lower
      production of HM-1 analogues. In the case of the acidic amino acid residue and
      basic amino acid residue substitutions, some analogues were produced in the same
      amount as and exhibited similar killing activity to that of the wild type HM-1.
      But the H35A HM-1 analogue had completely lost the killing activity, and D44A,
      K21A, K46A, R82A, R85A and R86A HM-1 showed highly decreased killing activities.
      These results strongly indicate the importance of histidine-35, aspartic acid-44,
      lysine-21, lysine-46, and C-terminal arginine residues in HM-1 for the killing
      activity.

PMID- 15858177
TI  - Two-cistronic expression plasmids for high-level gene expression in Escherichia
      coli preventing translational initiation inhibition caused by the intramolecular
      local secondary structure of mRNA.
AB  - Two-cistronic expression plasmids for the wild-type solubilized domain of porcine
      NADPH-cytochrome P450 reductase (PsCPR) gene in Escherichia coli were
      systematically constructed using a solubilized domain of porcine cytochrome b5
      gene (Psb5 gene) or a derivative of it as the first cistron to examine their
      utility for second gene expression preventing the translational inhibition caused
      by the intramolecular local secondary structure of mRNA at the ribosome-binding
      site (RBS). The mRNAs from the plasmids lacking an RBS for the second cistron
      (SD2) accumulated very low levels of PsCPR, while those from the plasmids having
      an SD2 accumulated higher levels of PsCPR. The level of accumulation of PsCPR by
      the mRNA from plasmid pCbSD-T-CPR-3, which has an SD2 upstream of the termination
      codon of the first cistron, was higher than for those with an SD2 in the
      intercistronic region. The predicted intramolecular local secondary structures at
      the SD2 of mRNAs from these plasmids were stable enough to cause translational
      initiation inhibition. These results indicate that the use of a two-cistronic
      expression plasmid is an effective way to overcome translational initiation
      inhibition. Improved plasmids, pCP1 and pCP2P, were constructed from pCbSD-T-CPR
      3. Using these plasmids, the solubilized donain of porcine NADH-cytochrome b5
      reductase was also highly accumulated on prevention of the translational
      initiation inhibition. These plasmids are expected to be useful tools for the
      comprehensive high-level expression of heterologous genes in E. coli cells.

PMID- 15858178
TI  - High-pressure-induced hemolysis in papain-digested human erythrocytes is
      suppressed by cross-linking of band 3 via anti-band 3 antibodies.
AB  - Upon exposure of human erythrocytes to a high pressure of 200 mPa, both hemolysis
      and vesiculation occur. The hemolysis of erythrocytes at 200 mPa was enhanced by
      removal of sialic acids from the membrane surface with papain. However, such
      enhancement was suppressed by cross-linking of band 3 via an anti-band 3 antibody
      (AB3A), which recognizes the exofacial domain of band 3, or by clustering of band
      3 via Zn2+. On the other hand, the size of high-pressure-induced vesicles
      increased from 423 to 525 nm in diameter upon exposure to papain of erythrocytes,
      but decreased to 444 nm with following treatment with AB3A. In these vesicles,
      the content of spectrin relative to band 3 was almost the same. Furthermore, the
      band 3-cytoskeleton interactions in erythrocyte membranes remained unaltered upon
      treatment with papain and AB3A. Flow cytometric analysis demonstrated that papain
      pretreated erythrocytes mainly produce open ghosts at 200 mPa and that the
      production of such open ghosts is suppressed by AB3A. Thus, upon removal of
      negative charges from the membrane surface, open ghosts are readily produced due
      to the release of larger vesicles under pressure. Upon cross-linking of band 3
      via AB3A, however, the release of smaller vesicles at 200 mPa is facilitated so
      that high-pressure-induced hemolysis is suppressed.

PMID- 15858179
TI  - Images in clinical medicine. Painless loss of vision after vomiting.

PMID- 15858180
TI  - Public access to NIH-funded research.

PMID- 15858181
TI  - Orchestration of iron homeostasis.

PMID- 15858182
TI  - A unifying mutation in chronic myeloproliferative disorders.

PMID- 15858183
TI  - They sent me here.

PMID- 15858184
TI  - Respiratory syncytial virus infection in elderly and high-risk adults.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is an increasingly recognized cause
      of illness in adults. Data on the epidemiology and clinical effects in community
      dwelling elderly persons and high-risk adults can help in assessing the need for
      vaccine development. METHODS: During four consecutive winters, we evaluated all
      respiratory illnesses in prospective cohorts of healthy elderly patients (> or
      =65 years of age) and high-risk adults (those with chronic heart or lung disease)
      and in patients hospitalized with acute cardiopulmonary conditions. RSV infection
      and influenza A were diagnosed on the basis of culture, reverse-transcriptase
      polymerase chain reaction, and serologic studies. RESULTS: A total of 608 healthy
      elderly patients and 540 high-risk adults were enrolled in prospective
      surveillance, and 1388 hospitalized patients were enrolled. A total of 2514
      illnesses were evaluated. RSV infection was identified in 102 patients in the
      prospective cohorts and 142 hospitalized patients, and influenza A was diagnosed
      in 44 patients in the prospective cohorts and 154 hospitalized patients. RSV
      infection developed annually in 3 to 7 percent of healthy elderly patients and in
      4 to 10 percent of high-risk adults. Among healthy elderly patients, RSV
      infection generated fewer office visits than influenza; however, the use of
      health care services by high-risk adults was similar in the two groups. In the
      hospitalized cohort, RSV infection and influenza A resulted in similar lengths of
      stay, rates of use of intensive care (15 percent and 12 percent, respectively),
      and mortality (8 percent and 7 percent, respectively). On the basis of the
      diagnostic codes of the International Classification of Diseases, 9th Revision,
      Clinical Modification at discharge, RSV infection accounted for 10.6 percent of
      hospitalizations for pneumonia, 11.4 percent for chronic obstructive pulmonary
      disease, 5.4 percent for congestive heart failure, and 7.2 percent for asthma.
      CONCLUSIONS: RSV infection is an important illness in elderly and high-risk
      adults, with a disease burden similar to that of nonpandemic influenza A in a
      population in which the prevalence of vaccination for influenza is high. An
      effective RSV vaccine may offer benefits for these adults.

PMID- 15858185
TI  - Multidetector-row computed tomography in suspected pulmonary embolism.
AB  - BACKGROUND: Single-detector-row computed tomography (CT) has a low sensitivity
      for pulmonary embolism and must be combined with venous-compression
      ultrasonography of the lower limbs. We evaluated whether the use of D-dimer
      measurement and multidetector-row CT, without lower-limb ultrasonography, might
      safely rule out pulmonary embolism. METHODS: We included 756 consecutive patients
      with clinically suspected pulmonary embolism from the emergency departments of
      three teaching hospitals and managed their cases according to a standardized
      sequential diagnostic strategy. All patients were followed for three months.
      RESULTS: Pulmonary embolism was detected in 194 of the 756 patients (26 percent).
      Among the 82 patients with a high clinical probability of pulmonary embolism,
      multidetector-row CT showed pulmonary embolism in 78, and 1 patient had proximal
      deep venous thrombosis and a CT scan that was negative for pulmonary embolism. Of
      the 674 patients without a high probability of pulmonary embolism, 232 (34
      percent) had a negative D-dimer assay and an uneventful follow-up; CT showed
      pulmonary embolism in 109 patients. CT and ultrasonography were negative in 318
      patients, of whom 3 had a definite thromboembolic event and 2 died of possible
      pulmonary embolism during follow-up (three-month risk of thromboembolism, 1.7
      percent; 95 percent confidence interval, 0.7 to 3.9). Two patients had proximal
      deep venous thrombosis and a negative CT scan (risk, 0.6 percent; 95 percent
      confidence interval, 0.2 to 2.2). The overall three-month risk of thromboembolism
      in patients without pulmonary embolism would have been 1.5 percent (95 percent
      confidence interval, 0.8 to 3.0) if the D-dimer assay and multidetector-row CT
      had been the only tests used to rule out pulmonary embolism and ultrasonography
      had not been performed. CONCLUSIONS: Our data indicate the potential clinical use
      of a diagnostic strategy for ruling out pulmonary embolism on the basis of D
      dimer testing and multidetector-row CT without lower-limb ultrasonography. A
      larger outcome study is needed before this approach can be adopted.

PMID- 15858186
TI  - Hemochromatosis and iron-overload screening in a racially diverse population.
AB  - BACKGROUND: Iron overload and hemochromatosis are common, treatable conditions.
      HFE genotypes, levels of serum ferritin, transferrin saturation values, and self
      reported medical history were studied in a multiethnic primary care population.
      METHODS: Participants were recruited from primary care practices and blood
      drawing laboratories. Blood samples were tested for transferrin saturation, serum
      ferritin, and C282Y and H63D mutations of the HFE gene. Before genetic screening,
      participants were asked whether they had a history of medical conditions related
      to iron overload. RESULTS: Of the 99,711 participants, 299 were homozygous for
      the C282Y mutation. The estimated prevalence of C282Y homozygotes was higher in
      non-Hispanic whites (0.44 percent) than in Native Americans (0.11 percent),
      Hispanics (0.027 percent), blacks (0.014 percent), Pacific Islanders (0.012
      percent), or Asians (0.000039 percent). Among participants who were homozygous
      for the C282Y mutation but in whom iron overload had not been diagnosed (227
      participants), serum ferritin levels were greater than 300 mug per liter in 78 of
      89 men (88 percent) and greater than 200 microg per liter in 79 of 138 women (57
      percent). Pacific Islanders and Asians had the highest geometric mean levels of
      serum ferritin and mean transferrin saturation despite having the lowest
      prevalence of C282Y homozygotes. There were 364 participants in whom iron
      overload had not been diagnosed (29 C282Y homozygotes) who had a serum ferritin
      level greater than 1000 microg per liter. Among men, C282Y homozygotes and
      compound heterozygotes were more likely to report a history of liver disease than
      were participants without HFE mutations. CONCLUSIONS: The C282Y mutation is most
      common in whites, and most C282Y homozygotes have elevations in serum ferritin
      levels and transferrin saturation. The C282Y mutation does not account for high
      mean serum ferritin levels and transferrin saturation values in nonwhites.

PMID- 15858187
TI  - A gain-of-function mutation of JAK2 in myeloproliferative disorders.
AB  - BACKGROUND: Polycythemia vera, essential thrombocythemia, and idiopathic
      myelofibrosis are clonal myeloproliferative disorders arising from a multipotent
      progenitor. The loss of heterozygosity (LOH) on the short arm of chromosome 9
      (9pLOH) in myeloproliferative disorders suggests that 9p harbors a mutation that
      contributes to the cause of clonal expansion of hematopoietic cells in these
      diseases. METHODS: We performed microsatellite mapping of the 9pLOH region and
      DNA sequencing in 244 patients with myeloproliferative disorders (128 with
      polycythemia vera, 93 with essential thrombocythemia, and 23 with idiopathic
      myelofibrosis). RESULTS: Microsatellite mapping identified a 9pLOH region that
      included the Janus kinase 2 (JAK2) gene. In patients with 9pLOH, JAK2 had a
      homozygous G-->T transversion, causing phenylalanine to be substituted for valine
      at position 617 of JAK2 (V617F). All 51 patients with 9pLOH had the V617F
      mutation. Of 193 patients without 9pLOH, 66 were heterozygous for V617F and 127
      did not have the mutation. The frequency of V617F was 65 percent among patients
      with polycythemia vera (83 of 128), 57 percent among patients with idiopathic
      myelofibrosis (13 of 23), and 23 percent among patients with essential
      thrombocythemia (21 of 93). V617F is a somatic mutation present in hematopoietic
      cells. Mitotic recombination probably causes both 9pLOH and the transition from
      heterozygosity to homozygosity for V617F. Genetic evidence and in vitro
      functional studies indicate that V617F gives hematopoietic precursors
      proliferative and survival advantages. Patients with the V617F mutation had a
      significantly longer duration of disease and a higher rate of complications
      (fibrosis, hemorrhage, and thrombosis) and treatment with cytoreductive therapy
      than patients with wild-type JAK2. CONCLUSIONS: A high proportion of patients
      with myeloproliferative disorders carry a dominant gain-of-function mutation of
      JAK2.

PMID- 15858188
TI  - Thrombosis of the cerebral veins and sinuses.

PMID- 15858189
TI  - Images in clinical medicine. Von Recklinghausen's disease and breast cancer.

PMID- 15858190
TI  - Case records of the Massachusetts General Hospital. Case 13-2005. A 48-year-old
      man with weakness of the limbs and multiple tumors of spinal nerves.

PMID- 15858191
TI  - RSV infection--not for kids only.

PMID- 15858192
TI  - Multislice computed tomography for pulmonary embolism--a technological marvel.

PMID- 15858193
TI  - Platelet-derived growth factor CC--a clinically useful angiogenic factor at last?

PMID- 15858194
TI  - Alcohol and cognitive function in older women.

PMID- 15858195
TI  - Nucleophosmin in acute myelogenous leukemia.

PMID- 15858196
TI  - Decline in mortality with varicella vaccination.

PMID- 15858197
TI  - Therapy for colorectal cancer.

PMID- 15858198
TI  - Insulin analogues.

PMID- 15858199
TI  - Return of renal function after endovascular treatment of aortic dissection.

PMID- 15858200
TI  - The cost of institutional review boards in academic medical centers.

PMID- 15858201
TI  - Host switch leads to emergence of Plasmodium vivax malaria in humans.
AB  - The geographical origin of Plasmodium vivax, the most widespread human malaria
      parasite, is controversial. Although genetic closeness to Asian primate malarias
      has been confirmed by phylogenetic analyses, genetic similarities between P.
      vivax and Plasmodium simium, a New World primate malaria, suggest that humans may
      have acquired P. vivax from New World monkeys or vice versa. Additionally, the
      near fixation of the Duffy-negative blood type (FY x B(null)/FY x B(null)) in
      West and Central Africa, consistent with directional selection, and the
      association of Duffy negativity with complete resistance to vivax malaria suggest
      a prolonged period of host-parasite coevolution in Africa. Here we use Bayesian
      and likelihood methods in conjunction with cophylogeny mapping to reconstruct the
      genetic and coevolutionary history of P. vivax from the complete mitochondrial
      genome of 176 isolates as well as several closely related Plasmodium species.
      Taken together, a haplotype network, parasite migration patterns, demographic
      history, and cophylogeny mapping support an Asian origin via a host switch from
      macaque monkeys.

PMID- 15858202
TI  - cimp1, a novel astacin family metalloproteinase gene from East African cichlids,
      is differentially expressed between species during growth.
AB  - Lake Victoria cichlid fishes are excellent examples of explosive adaptive
      radiation. Although Lake Victoria cichlids are believed to have arisen during a
      short period (approximately 14,000 years), they have various species-specific
      phenotypes. One important phenotype that distinguishes each species is the shape
      of the jaw, which has diverged to adapt to the wide variety of trophic habitats
      present in the lake. Here we demonstrate a new approach to investigate the
      diversification of cichlid jaw morphology at the genetic level by examining
      differentially expressed genes. We used a DNA chip to compare gene expression
      levels between closely related cichlid fishes. This analysis indicated that the
      expression of some genes differed in the larvae of two cichlid species. One such
      clone encodes a new astacin family metalloproteinase. The expression level of the
      isolated gene, named cimp1, was analyzed in more detail by real-time quantitative
      reverse transcription-polymerase chain reaction. A significant difference in
      cimp1 expression was observed between two Haplochromis cichlid species during
      development. Using in situ hybridization, we found that this gene is expressed
      only in head and gill epithelia. Biochemical analysis showed that cichlid
      metalloproteinase 1 (CiMP1) has proteolytic activity, a common attribute of all
      astacin family proteins. Because some astacin family proteins contribute to
      morphogenesis in animals, CiMP1 is expected to participate in species-specific
      head morphogenesis in cichlids. This is the first study to demonstrate that
      differentially expressed genes among cichlids can be identified using a DNA chip.

PMID- 15858203
TI  - Analysis of the reticulon gene family demonstrates the absence of the neurite
      growth inhibitor Nogo-A in fish.
AB  - Reticulons (RTNs) are a family of evolutionary conserved proteins with four RTN
      paralogs (RTN1, RTN2, RTN3, and RTN4) present in land vertebrates. While the
      exact functions of RTN1 to RTN3 are unknown, mammalian RTN4-A/Nogo-A was shown to
      inhibit the regeneration of severed axons in the mammalian central nervous system
      (CNS). This inhibitory function is exerted via two distinct regions, one within
      the Nogo-A-specific N-terminus and the other in the conserved reticulon homology
      domain (RHD). In contrast to mammals, fish are capable of CNS axon regeneration.
      We performed detailed analyses of the fish rtn gene family to determine whether
      this regeneration ability correlates with the absence of the neurite growth
      inhibitory protein Nogo-A. A total of 7 rtn genes were identified in zebrafish, 6
      in pufferfish, and 30 in eight additional fish species. Phylogenetic and syntenic
      relationships indicate that the identified fish rtn genes are orthologs of
      mammalian RTN1, RTN2, RTN3, and RTN4 and that several paralogous fish genes
      (e.g., rtn4 and rtn6) resulted from genome duplication events early in
      actinopterygian evolution. Accordingly, sequences homologous to the conserved
      RTN4/Nogo RHD are present in two fish genes, rtn4 and rtn6. However, sequences
      comparable to the first approximately 1,000 amino acids of mammalian Nogo-A
      including a major neurite growth inhibitory region are absent in zebrafish. This
      result is in accordance with functional data showing that axon growth inhibitory
      molecules are less prominent in fish oligodendrocytes and CNS myelin compared to
      mammals.

PMID- 15858204
TI  - Networks of coevolving sites in structural and functional domains of serpin
      proteins.
AB  - Amino acids do not occur randomly in proteins; rather, their occurrence at any
      given site is strongly influenced by the amino acid composition at other sites,
      the structural and functional aspects of the region of the protein in which they
      occur, and the evolutionary history of the protein. The goal of our research
      study is to identify networks of coevolving sites within the serpin proteins
      (serine protease inhibitors) and classify them as being caused by structural
      functional constraints or by evolutionary history. To address this, a matrix of
      pairwise normalized mutual information (NMI) values was computed among amino acid
      sites for the serpin proteins. The NMI matrix was partitioned into orthogonal
      patterns of amino acid variability by factor analysis. Each common factor pattern
      was interpreted as having phylogenetic and/or structural-functional explanations.
      In addition, we used a bootstrap factor analysis technique to limit the effects
      of phylogenetic history on our factor patterns. Our results show an extensive
      network of correlations among amino acid sites in key functional regions
      (reactive center loop, shutter, and breach). Additionally, we have discovered
      long-range coevolution for packed amino acids within the serpin protein core.
      Lastly, we have discovered a group of serpin sites which coevolve in the
      hydrophobic core region (s5B and s4B) and appear to represent sites important for
      formation of the "native" instead of the "latent" serpin structure. This research
      provides a better understanding on how protein structure evolves; in particular,
      it elucidates the selective forces creating coevolution among protein sites.

PMID- 15858206
TI  - Biogeography of luminous marine ostracod driven irreversibly by the Japan
      current.
AB  - The biogeography of the luminous marine ostracod Vargula hilgendorfii, also
      called "Umihotaru," shows that this organism may have arrived relatively recently
      on the Japanese islands during the final glacier period approximately 10,000
      years ago. Phylogenetic relationships also strongly indicate that the Japan
      Current drove the Umihotaru ostracod northward. It is evident that the Umihotaru
      ostracod spread rapidly to the major Japanese islands 3,000 km north, whereas its
      spread was slow in the southwest of the Japanese islands, covering a distance of
      400 km. The meandering of the Japan Current, where it passes by the Tokara Gap at
      28 degrees N latitude, may be a barrier to Umihotaru ostracod extension.

PMID- 15858207
TI  - Evolution of noncoding and silent coding sites in the Plasmodium falciparum and
      Plasmodium reichenowi genomes.
AB  - We compared levels of sequence divergence between fourfold synonymous coding
      sites and noncoding sites from the intergenic and intronic regions of the
      Plasmodium falciparum and Plasmodium reichenowi genomes. We observed significant
      differences in the level of divergence between these classes of silent sites.
      Fourfold synonymous coding sites exhibited the highest level of sequence
      divergence, followed by introns, and then intergenic sequences. This pattern of
      relative divergence rates has been observed in primate genomes but was unexpected
      in Plasmodium due to a paucity of variation at silent sites in P. falciparum and
      the corollary hypothesis that silent sites in this genome may be subject to
      atypical selective constraints. Exclusion of hypermutable CpG dinucleotides
      reduces the divergence level of synonymous coding sites to that of intergenic
      sites but does not diminish the significantly higher divergence level of introns
      relative to intergenic sites. A greater than expected incidence of CpG
      dinucleotides in intergenic regions less than 500 bp from genes may indicate
      selective maintenance of regulatory motifs containing CpGs. Divergence rates of
      different classes of silent sites in these Plasmodium genomes are determined by a
      combination of mutational and selective pressures.

PMID- 15858208
TI  - Phenotypic and genotypic expression of self-incompatibility haplotypes in
      Arabidopsis lyrata suggests unique origin of alleles in different dominance
      classes.
AB  - The highly divergent alleles of the SRK gene in outcrossing Arabidopsis lyrata
      have provided important insights into the evolutionary history of self
      incompatibility (SI) alleles and serve as an ideal model for studies of the
      evolutionary and molecular interactions between alleles in cell-cell recognition
      systems in general. One tantalizing question is how new specificities arise in
      systems that require coordination between male and female components. Allelic
      recruitment via gene conversion has been proposed as one possibility, based on
      the division of DNA sequences at the SRK locus into two distinctive groups: (1)
      sequences whose relationships are not well resolved and display the long branch
      lengths expected for a gene under balancing selection (Class A); and (2)
      sequences falling into a well-supported group with shorter branch lengths (Class
      B) that are closely related to an unlinked paralogous locus. The purpose of this
      study was to determine if differences in phenotype (site of expression assayed
      using allele-specific reverse transcription-polymerase chain reaction) or
      function (dominance relationships assayed through controlled pollinations)
      accompany the sequence-based classification. Expression of Class A alleles was
      restricted to floral tissues, as predicted for genes involved in the SI response.
      In contrast, Class B alleles, despite being tightly linked to the SI phenotype,
      were unexpectedly expressed in both leaves and floral tissues; the same pattern
      found for a related unlinked paralogous sequence. Whereas Class A included
      haplotypes in three different dominance classes, all Class B haplotypes were
      found to be recessive to all except one Class A haplotype. In addition, mapping
      of expression and dominance patterns onto an S-domain-based genealogy suggested
      that allelic dominance may be determined more by evolutionary history than by
      frequency-dependent selection for lowered dominance as some theories suggest. The
      possibility that interlocus gene conversion might have contributed to allelic
      diversity is discussed.

PMID- 15858209
TI  - Reciprocal fusions of two genes in the formaldehyde detoxification pathway in
      ciliates and diatoms.
AB  - During the course of a pilot genome project for the ciliate Oxytricha trifallax,
      we discovered a fusion gene never before described in any taxa. This gene, FSF1,
      encodes a putative fusion protein comprising an entire formaldehyde dehydrogenase
      (FALDH) homolog at one end and an S-formylglutathione hydrolase (SFGH) homolog at
      the other, two proteins that catalyze serial steps in the formaldehyde
      detoxification pathway. We confirmed the presence of the Oxytricha fusion gene in
      vivo and detected transcripts of the full-length fusion gene. A survey of other
      large-scale sequencing projects revealed a similar fusion protein in a distantly
      related ciliate, Tetrahymena thermophila, and a possible fusion of these two
      genes in the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana, but
      in the reverse order, with the SFGH domain encoded upstream of the FALDH domain.
      Orthologs of these fusion proteins may be widespread within the ciliates and
      diatoms.

PMID- 15858210
TI  - The Trichoplax PaxB gene: a putative Proto-PaxA/B/C gene predating the origin of
      nerve and sensory cells.
AB  - Pax genes play key regulatory roles in embryonic and sensory organ development in
      metazoans but their evolution and ancestral functions remain widely unresolved.
      We have isolated a Pax gene from Placozoa, beside Porifera the only metazoan
      phylum that completely lacks nerve and sensory cells or organs. These simplest
      known metazoans also lack any kind of symmetry, organs, extracellular matrix,
      basal lamina, muscle cells, and main body axis. The isolated Pax gene from
      Trichoplax adhaerens harbors a paired domain, an octapeptide, and a full-length
      homeodomain. It displays structural features not only of PaxB and Pax2/5/8-like
      genes but also of PaxC and Pax6 genes. Conserved splice sites between Placozoa,
      Cnidaria, and triploblasts, mark the ancient origin of intron structures.
      Phylogenetic analyses demonstrate that the Trichoplax PaxB gene, TriPaxB, is
      basal not only to all other known PaxB genes but also to PaxA and PaxC genes and
      their relatives in triploblasts (namely Pax2/5/8, Pax4/6, and Poxneuro). TriPaxB
      is expressed in distinct cell patches near the outer edge of the animal body,
      where undifferentiated and possibly multipotent cells are found. This expression
      pattern indicates a developmental role in cell-type specification and/or
      differentiation, probably in specifying-determining fiber cells, which are
      regarded as proto-neural/muscle cells in Trichoplax. While PaxB, Pax2/5/8, and
      Pax6 genes have been linked to nerve cell and sensory system/organ development in
      virtually all animals investigated so far, our study suggests that Pax genes
      predate the origin of nerve and sensory cells.

PMID- 15858211
TI  - Shields down.

PMID- 15858212
TI  - Optimistic for longevity.

PMID- 15858213
TI  - The art and science of anti-aging therapies.
AB  - A meeting entitled "The Art and Science of Anti-Aging Therapies: Convergence of
      Theory and Practice" took place on 18 and 19 March 2005 at the University of
      Pennsylvania School of Medicine. The symposium was held for health care
      professionals, researchers, and consumers to provide them with information about
      current trends in anti-aging therapies. The program, which combined medical,
      surgical, and nonpharmacological approaches to healthy successful aging, gave
      attendees the opportunity to make sense of the issues at hand and to sort out
      safe treatments from perilous quick fixes.

PMID- 15858214
TI  - Regulation of neonatal Sertoli cell development by thyroid hormone receptor
      alpha1.
AB  - Neonatal hypothyroidism increases adult Sertoli cell populations by extending
      Sertoli cell proliferation. Conversely, hyperthyroidism induces premature
      cessation of Sertoli cell proliferation and stimulates maturational events like
      seminiferous tubule canalization. Thyroid hormone receptors alpha1 and beta1,
      which are commonly referred to as TRalpha1 and TRbeta1, respectively, are
      expressed in neonatal Sertoli cells. We determined the relative roles of TRalpha1
      and TRbeta1 in the thyroid hormone effect on testicular development and Sertoli
      cell proliferation using Thra knockout (TRalphaKO), Thrb knockout (TRbetaKO), and
      wild-type (WT) mice. Triiodothyronine (T3) treatment from birth until Postnatal
      Day 10 reduced Sertoli cell proliferation to minimal levels in WT and TRbetaKO
      mice versus that in their untreated controls, whereas T3 had a diminished effect
      on TRalphaKO Sertoli cell proliferation. Seminiferous tubule patency and luminal
      diameter were increased in T3-treated WT and TRbetaKO testes. In contrast, T3 had
      no effect on these parameters in TRalphaKO mice. In untreated adult TRalphaKO
      mice, Sertoli cell number, testis weight, and daily sperm production were
      increased or trended toward an increase, but the increase in magnitude was
      smaller than that seen in WT mice following neonatal hypothyroidism. Conversely,
      in TRbetaKO mice, Sertoli cell number, testis weight, and daily sperm production
      were similar to those in untreated WT mice. In addition, Sertoli cell number and
      testis weight in adult WT and TRbetaKO mice showed comparable increases following
      hypothyroidism. Our results show that TRalphaKO mice have testicular effects
      similar to those seen in WT mice following neonatal hypothyroidism and that
      TRbetaKO mice, but not TRalphaKO mice, have normal Sertoli cell responsiveness to
      T3. Thus, effects of exogenous manipulation of T3 on neonatal Sertoli cell
      development are predominately mediated through TRalpha1.

PMID- 15858215
TI  - Regulation of Sertoli-germ cell adherens junction dynamics in the testis via the
      nitric oxide synthase (NOS)/cGMP/protein kinase G (PRKG)/beta-catenin (CATNB)
      signaling pathway: an in vitro and in vivo study.
AB  - During spermatogenesis, extensive restructuring of cell junctions takes place in
      the seminiferous epithelium to facilitate germ cell movement. However, the
      mechanism that regulates this event remains largely unknown. Recent studies have
      shown that nitric oxide (NO) likely regulates tight junction (TJ) dynamics in the
      testis via the cGMP/protein kinase G (cGMP-dependent protein kinase, PRKG)
      signaling pathway. Due to the proximity of TJ and adherens junctions (AJ) in the
      testis, in particular at the blood-testis barrier, it is of interest to
      investigate if NO can affect AJ dynamics. Studies using Sertoli-germ cell
      cocultures in vitro have shown that the levels of NOS (nitric oxide synthase),
      cGMP, and PRKG were induced when anchoring junctions were being established.
      Using an in vivo model in which adult rats were treated with adjudin [a molecule
      that induces adherens junction disruption, formerly called AF-2364, 1-(2,4
      dichlorobenzyl)-IH-indazole-3-carbohydrazide], the event of AJ disruption was
      also associated with a transient iNOS (inducible nitric oxide synthase, NOS2)
      induction. Immunohistochemistry has illustrated that NOS2 was intensely
      accumulated in Sertoli and germ cells in the epithelium during adjudin-induced
      germ cell loss, with a concomitant accumulation of intracellular cGMP and an
      induction of PRKG but not cAMP or protein kinase A (cAMP-dependent protein
      kinase, PRKA). To identify the NOS-mediated downstream signaling partners,
      coimmunoprecipitation was used to demonstrate that NOS2 and eNOS (endothelial
      nitric oxide synthase, NOS3) were structurally associated with the N-cadherin
      (CDH2)/beta-catenin (CATNB)/actin complex but not the nectin-3 (poliovirus
      receptor-related 3, PVRL 3)/afadin (myeloid/lymphoid or mixed lineage-leukemia
      tranlocation to 4 homolog, MLLT4) nor the integrin beta1 (ITB1)-mediated protein
      complexes, illustrating the spatial vicinity of NOS with selected AJ-protein
      complexes. Interestingly, CDH2 and CATNB were shown to dissociate from NOS during
      the adjudin-mediated AJ disruption, implicating the CDH2/CATNB protein complex is
      the likely downstream target of the NO signaling. Furthermore, PRKG, the
      downstream signaling protein of NOS, was shown to interact with CATNB in the rat
      testis. Perhaps the most important of all, pretreatment of testes with KT5823, a
      specific PRKG inhibitor, can indeed delay the adjudin-induced germ cell loss,
      further validating NOS/NO regulates Sertoli-germ cell AJ dynamics via the
      cGMP/PRKG pathway. These results illustrate that the CDH2/CATNB-mediated adhesion
      function in the testis is regulated, at least in part, via the
      NOS/cGMP/PRKG/CATNB pathway.

PMID- 15858216
TI  - Inhibition of trophoblast cell invasion by TGFB1, 2, and 3 is associated with a
      decrease in active proteases.
AB  - Invasion of extravillous trophoblast cells into the uterus in human pregnancy is
      tightly regulated. The transforming growth factor-beta (TGFB) family has been
      suggested to play a role in controlling this process. We hypothesized that TGFB1,
      2, and 3 would inhibit the invasive capacity of extravillous trophoblast cells.
      We also studied trophoblast apoptosis and proliferation and secreted protease
      levels as potential mechanisms by which these cytokines may act. Inhibition of
      endogenous TGFB1, 2, and 3 with neutralizing antibodies increased the invasive
      capacity of extravillous trophoblast cells derived from placental explants.
      Similarly, addition of exogenous TGFB1, 2, and 3 inhibited the invasive capacity
      of these cells in a dose-dependent manner. Proliferation of trophoblast in the
      placental explants did not alter in response to any of the cytokines tested.
      Apoptosis of villous and extravillous trophoblast did not alter in response to
      TGFB1, 2, and 3. There was a reduction in secreted levels of matrix
      metalloproteinase (MMP) 9 and urokinase plasminogen activator in response to all
      three cytokines. MMP2 and tissue inhibitor of metalloproteinase 1 and 3 levels
      were not altered. These results suggest that TGFB1, 2, and 3 inhibit trophoblast
      invasion by a mechanism dependent on reduced protease activity.

PMID- 15858217
TI  - Serotonin and its antidepressant-sensitive transport in mouse cumulus-oocyte
      complexes and early embryos.
AB  - Serotonin (5-hydroxytryptamine [5-HT]), is a neurohormone found in various
      nonneural tissues, including the gonads of many invertebrates, in which it
      regulates spawning and oocyte meiotic maturation. The possibility that a local
      serotonergic network might also exist in the female gonads of vertebrate species,
      including mammals, remains poorly documented. To clarify this possibility, we
      investigated mouse cumulus cells, oocytes, and embryos for three key serotonergic
      components, namely, 5-HT itself; the rate-limiting enzyme for its production,
      tryptophan hydroxylase 1 (TPH1); and the 5-HT-specific transporter (SLC6A4)
      required for modulating its cellular effects. Using a combination of reverse
      transcription-polymerase chain reaction analysis and immunofluorescence confocal
      microscopy, we showed that mouse cumulus cells, oocytes, and embryos contain 5-HT
      and SLC6A4, while only cumulus cells possess the 5-HT-producing enzyme TPH1 and
      may thus be the local source of 5-HT observed in their neighboring cells. With a
      semiquantitative assay in single cells, we demonstrated that 5-HT can actively be
      taken up by isolated oocytes when it is supplied exogenously in vitro. This 5-HT
      transport in isolated oocytes is driven by a classical serotonin transporter,
      expressed up to the blastocyst stage, that is sensitive to the antidepressants
      fluoxetine and fluvoxamine, which belong to the selective serotonin reuptake
      inhibitor family. All together, our results show that 5-HT may be produced
      locally by cumulus cells and that it can be actively taken up by mammalian
      oocytes and embryos as part of a likely larger serotonergic network possibly
      regulating various developmental processes much earlier than previously thought.

PMID- 15858218
TI  - Identification of cytochrome-b5 reductase as the enzyme responsible for NADH
      dependent lucigenin chemiluminescence in human spermatozoa.
AB  - Lucigenin-dependent chemiluminescence together with 2-[4-iodophenyl]-3-[4
      nitrophenyl]-5-[2,4-disulfophenyl]-2H tetrazolium monosodium salt (WST-1)
      reduction can be detected following addition of NADH to many cell types,
      including human sperm suspensions. Although many reports suggest that such a
      phenomenon is due to reactive oxygen species production, other oxygen detecting
      metabolite probes, such as MCLA and luminol, do not produce a chemiluminescent
      signal in this model system. The enzyme responsible for NADH-dependent lucigenin
      chemiluminescence was purified and identified as cytochrome-b5 reductase. In
      support of this concept, COS-7 cells overexpressing cytochrome-b5 reductase
      displayed at least a 3-fold increase in the previously mentioned activity
      compared with mock-transfected cells. Fractions containing cytochrome-b5
      reductase were capable of inducing both lucigenin-dependent chemiluminescence and
      WST-1 reduction. Oxygen radicals clearly did not mediate the cytochrome b5
      mediated activation of these probes in vitro since neither luminol nor MCLA gave
      a chemiluminescence response in the presence of the enzyme and the cofactor NADH.
      These results emphasize the importance of the direct NADH-dependent reduction of
      these putative superoxide-sensitive probes by cytochrome-b5 reductase even though
      this enzyme does not, on its own accord, produce reactive oxygen species.

PMID- 15858219
TI  - Highly selective enrichment of phosphorylated peptides from peptide mixtures
      using titanium dioxide microcolumns.
AB  - Reversible phosphorylation of proteins regulates the majority of all cellular
      processes, e.g. proliferation, differentiation, and apoptosis. A fundamental
      understanding of these biological processes at the molecular level requires
      characterization of the phosphorylated proteins. Phosphorylation is often
      substoichiometric, and an enrichment procedure of phosphorylated peptides derived
      from phosphorylated proteins is a necessary prerequisite for the characterization
      of such peptides by modern mass spectrometric methods. We report a highly
      selective enrichment procedure for phosphorylated peptides based on
      TiO2microcolumns and peptide loading in 2,5-dihydroxybenzoic acid (DHB). The
      effect of DHB was a very efficient reduction in the binding of nonphosphorylated
      peptides to TiO2 while retaining its high binding affinity for phosphorylated
      peptides. Thus, inclusion of DHB dramatically increased the selectivity of the
      enrichment of phosphorylated peptides by TiO2. We demonstrated that this new
      procedure was more selective for binding phosphorylated peptides than IMAC using
      MALDI mass spectrometry. In addition, we showed that LC-ESI-MSMS was biased
      toward monophosphorylated peptides, whereas MALDI MS was not. Other substituted
      aromatic carboxylic acids were also capable of specifically reducing binding of
      nonphosphorylated peptides, whereas phosphoric acid reduced binding of both
      phosphorylated and nonphosphorylated peptides. A putative mechanism for this
      intriguing effect is presented.

PMID- 15858220
TI  - The effect of the food matrix on in vivo immune responses to purified peanut
      allergens.
AB  - There is little knowledge about the factors that determine the allergenicity of
      food proteins. One aspect that remains to be elucidated is the effect of the food
      matrix on immune responses to food proteins. To study the intrinsic
      immunogenicity of allergens and the influence of the food matrix, purified peanut
      allergens (Ara h 1, Ara h 2, Ara h 3, or Ara h 6) and a whole peanut extract (PE)
      were tested in the popliteal lymph node assay (PLNA) and in an oral model of
      peanut hypersensitivity. In the PLNA, peanut proteins were injected into the hind
      footpad of BALB/c mice; in the oral exposure experiments C3H/HeOuJ mice were
      gavaged weekly with PE or allergens in the presence of cholera toxin (CT). Upon
      footpad injection, none of the allergens induced significant immune activation.
      In contrast, PE induced an increase in cell number, cytokine production, and
      activation of antigen-presenting cells. Furthermore, the presence of a food
      matrix enhanced the immune response to the individual allergens. Oral exposure to
      the purified allergens in the presence of CT induced specific IgE responses,
      irrespective of the presence of a food matrix. These results suggest that
      purified peanut allergens possess little intrinsic immune-stimulating capacity in
      contrast to a whole PE. Moreover, the data indicate that the food matrix can
      influence responses to individual proteins and, therefore, the food matrix must
      be taken into account when developing models for allergenic potential assessment.

PMID- 15858221
TI  - The tobacco alkaloid nicotine demonstrates genotoxicity in human tonsillar tissue
      and lymphocytes.
AB  - Recent studies suggest a direct contribution of nicotine, the addictive component
      of tobacco and tobacco smoke, to human carcinogenesis. To assess the genotoxicity
      of nicotine, the DNA-damaging effect on human lymphocytes and target cells from
      lymphatic tissue of the palatine tonsils from 10 healthy patients was tested with
      the alkaline single-cell microgel electrophoresis (Comet) assay. The degree of
      DNA migration, a measure of possible DNA single strand breaks, alkali labile
      sites, and incomplete excision repair sites, was expressed as the Olive tail
      moment, the percentage of DNA in the tail, and the tail length. One hour exposure
      to nicotine at 0.125, 0.25, 0.5, 1, 2, and 4 mM induced a statistically
      significant dose-dependent increase of DNA migration up to 3.8-fold and 3.2-fold
      in tonsillar cells and lymphocytes, respectively. The lowest concentration
      eliciting significant DNA damage was 0.5 mM nicotine. The genotoxic effect was
      confirmed in a second series of experiments using nicotine of high purity from
      two different suppliers. There were no significant differences between the two
      series, excluding artifacts from the source of nicotine. Finally, DNA damage by
      nicotine was compared in cells incubated in medium strictly adjusted to neutral
      pH, with non-adjusted medium becoming alkaline with increasing nicotine
      concentrations. Again no differences in DNA migration were observed. The data
      indicate that nicotine expresses significant direct genotoxic effects in human
      target cells in vitro. However, no differences in DNA damage were observed in
      cells from smokers and nonsmokers incubated without nicotine. The lack of higher
      DNA damage in smokers compared to nonsmokers could be a question of nicotine
      dose, rapid DNA repair, or interactions with other smoke constituents. These
      results require further investigations on the contribution of nicotine to tobacco
      carcinogenesis.

PMID- 15858222
TI  - Valproic acid II: effects on oxidative stress, mitochondrial membrane potential,
      and cytotoxicity in glutathione-depleted rat hepatocytes.
AB  - Oxidative stress has been associated with valproic acid (VPA) treatment, and
      mitochondrial dysfunction has been implicated in the pathogenesis of VPA
      idiosyncratic hepatotoxicity. The present study investigated the effect of VPA
      and the role of GSH on oxidative stress, mitochondrial membrane potential, and
      toxicity in freshly isolated rat hepatocytes. Hepatocytes were isolated from
      Sprague-Dawley rats, and total levels of glutathione (GSH) reduced by
      pretreatment with a combination of L-buthionine sulfoximine (2 mM) and
      diethylmaleate (0.5 mM) prior to VPA (0-1000 microg/ml) treatment. Oxidative
      stress was determined by measuring the levels of 15-F(2t)-isoprostane (15-F(2t)
      IsoP) and 2',7'-dichlorofluorescein (DCF). Mitochondrial membrane potential
      (Deltapsi(m)) was determined by using the dual-fluorescent dye JC-1, and cell
      viability was evaluated by the water-soluble tetrazolium salt WST-1 assay.
      Exposure of rat hepatocytes to VPA (0-1000 mug/ml) resulted in a time- and dose
      dependent increase in 15-F(2t)-IsoP and DCF fluorescence, and these levels were
      further elevated in GSH-reduced hepatocytes. In control hepatocytes, VPA had no
      effect on cell viability; however, significant cytotoxicity was observed in the
      glutathione-depleted hepatocytes treated with 1000 mug/ml VPA. The Deltapsi(m)
      was only reduced in glutathione-reduced hepatocytes at 500 and 1000 microg/ml
      VPA. Our novel findings indicate that acute treatment of freshly isolated rat
      hepatocytes with VPA resulted in oxidative stress, which occurred in the absence
      of cytotoxicity, and that glutathione confers protection to hepatocytes against
      mitochondrial damage by VPA.

PMID- 15858223
TI  - Valproic acid I: time course of lipid peroxidation biomarkers, liver toxicity,
      and valproic acid metabolite levels in rats.
AB  - A single dose of valproic acid (VPA), which is a widely used antiepileptic drug,
      is associated with oxidative stress in rats, as recently demonstrated by elevated
      levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP). To determine whether there was a
      temporal relationship between VPA-associated oxidative stress and hepatotoxicity,
      adult male Sprague-Dawley rats were treated ip with VPA (500 mg/kg) or 0.9%
      saline (vehicle) once daily for 2, 4, 7, 10, or 14 days. Oxidative stress was
      assessed by determining plasma and liver levels of 15-F(2t)-IsoP, lipid
      hydroperoxides (LPO), and thiobarbituric acid reactive substances (TBARs). Plasma
      and liver 15-F(2t)-IsoP were elevated and reached a plateau after day 2 of VPA
      treatment compared to control. Liver LPO levels were not elevated until day 7 of
      treatment (1.8-fold versus control, p < 0.05). Liver and plasma TBARs were not
      increased until 14 days (2-fold vs. control, p < 0.05). Liver toxicity was
      evaluated based on serum levels of alpha-glutathione S-transferase (alpha-GST)
      and by histology. Serum alpha-GST levels were significantly elevated by day 4,
      which corresponded to hepatotoxicity as shown by the increasing incidence of
      inflammation of the liver capsule, necrosis, and steatosis throughout the study.
      The liver levels of beta-oxidation metabolites of VPA were decreased by day 14,
      while the levels of 4-ene-VPA and (E)-2,4-diene-VPA were not elevated throughout
      the study. Overall, these findings indicate that VPA treatment results in
      oxidative stress, as measured by levels of 15-F(2t)-IsoP, which precedes the
      onset of necrosis, steatosis, and elevated levels of serum alpha-GST.

PMID- 15858224
TI  - Altered retinoid metabolism in female Long-Evans and Han/Wistar rats following
      long-term 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treatment.
AB  - This study investigated the effects of long-term low-dose 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) exposure on retinoid, thyroid hormone, and
      vitamin D homeostasis in Long-Evans and Han/Wistar rats using a tumor promotion
      exposure protocol. Female rats (ten/group) were partially hepatectomized,
      initiated with nitrosodiethylamine (NDEA), and given TCDD once per week by sc
      injection for 20 weeks at calculated daily doses of 0, 1, 10, 100, or 1000 ng/kg
      bw/day. Groups of nonhepatectomized/uninitiated rats (five/group) were
      identically maintained. After 20 weeks, the rats were killed, and apolar retinoid
      levels were determined in the liver and kidneys. No consistent differences were
      seen between partially hepatectomized/initiated and nonhepatectomized/uninitiated
      animals with respect to apolar retinoid levels or hepatic TCDD concentration.
      Further analyses of polar and apolar retinoid levels in liver, plasma, and
      kidney, as well as free thyroxine (FT4) and vitamin D (25-OH-D(3)) concentrations
      were carried out in partially hepatectomized/inititated animals. In Long-Evans
      rats, TCDD exposure dose-dependently decreased hepatic retinyl ester
      concentrations at doses of 1-100 ng/kg bw/day. Likewise, hepatic all-trans
      retinoic acid (all-trans-RA) concentration was decreased 39 and 54% at 10 and 100
      ng/kg bw/day respectively, whereas 9-cis-4-oxo-13,14-dihydro-retinoic acid (9-cis
      4-oxo-13,14-dihydro-RA), a recently discovered retinoic acid metabolite, was
      decreased approximately 60% in the liver at 1 ng/kg bw/day. TCDD dose-dependently
      increased plasma retinol and kidney retinol concentrations, whereas all-trans-RA
      concentration was also increased in the plasma and kidney at 10 and 100 ng/kg
      bw/day. Plasma 9-cis-4-oxo-13,14-dihydro-RA was decreased to below detection
      limits from doses of 1 ng/kg bw/day TCDD. A qualitatively similar pattern of
      retinoid disruption was observed in the Han/Wistar rat strain following TCDD
      exposure. FT4 was decreased to a similar extent in both strains, whereas 25-OH
      D(3) was decreased only at 100 ng/kg bw/day in Long-Evans rats. Together these
      results show that TCDD disrupts both retinoid storage and metabolism of retinoic
      acid and retinoic acid metabolites in liver, kidney, and plasma from doses as low
      as 1 ng/kg bw/day. Furthermore, 9-cis-4-oxo-13,14-dihydro-RA was identified as a
      novel and sensitive indicator of TCDD exposure, in a resistant and sensitive rat
      strain, thereby extending the database of low-dose TCDD effects.

PMID- 15858226
TI  - Gene expression in normal human bronchial epithelial (NHBE) cells following in
      vitro exposure to cigarette smoke condensate.
AB  - Cigarettes that burn tobacco produce a complex mixture of chemicals, including
      mutagens and carcinogens. Cigarettes that primarily heat tobacco produce smoke
      with marked reductions in the amount of mutagens and carcinogens and demonstrate
      reduced mutagenicity and carcinogenicity in a battery of toxicological assays.
      Chemically induced oxidative stress, DNA damage, and inflammation may alter cell
      cycle regulation and are important biological events in the carcinogenic process.
      The objective of this study was to characterize and compare the effects of smoke
      condensates from cigarettes that burn tobacco and those that primarily heat
      tobacco on gene expression in NHBE cells. For this comparison, we used
      quantitative RT/PCR and further evaluated the effects on cell cycling using flow
      cytometry. Cigarette smoke condensates (CSCs) were prepared from Kentucky 1R4F
      cigarettes (a tobacco-burning product designed to represent the average full
      flavor, low "tar" cigarette in the US market) and Eclipse (a cigarette that
      primarily heats tobacco) using FTC machine smoking conditions. The CSC from 1R4F
      cigarettes induced statistically significant increases in the mRNA levels of
      genes responsive to DNA damage (GADD45) and involved in cell cycle regulation
      (p21;WAF1/CIP1), compared to the CSC from Eclipse cigarettes. In addition, genes
      coding for cyclooxygenase-2 (COX-2) and interleukin 8 (IL-8), which are
      associated with oxidative stress and inflammation, respectively, were increased
      statistically significantly more by CSC from 1R4F than by that from Eclipse.
      Furthermore, a dose-dependent increase in IL-8 protein secretion into cell
      culture media was stimulated by 1R4F exposure, whereas minimal IL-8 protein was
      secreted after Eclipse treatment. The biological relevance of the differential
      effect on gene expression was reflected in differential cell cycle regulation, as
      cells exposed to 1R4F CSC exhibited more significant S phase and G2 phase
      accumulation than cells exposed to Eclipse CSC. These data indicate that the
      simplified smoke chemistry of the tobacco-heating Eclipse cigarette yields
      statistically significant reductions in the expression of key genes involved in
      DNA damage, oxidative stress, inflammatory response, and cell cycle regulation in
      normal human bronchial epithelial cells compared to a representative tobacco
      burning cigarette.

PMID- 15858227
TI  - Comparisons of brain, uterus, and liver mRNA expression for cytochrome p450s, DNA
      methyltransferase-1, and catechol-o-methyltransferase in prepubertal female
      Sprague-Dawley rats exposed to a mixture of aryl hydrocarbon receptor agonists.
AB  - Non-ortho polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins
      (PCDDs), and polychlorinated dibenzofurans (PCDFs) are ubiquitous environmental
      contaminants that exert their toxicity mostly through activation of the aryl
      hydrocarbon receptor (AhR), and are referred to as AhR agonists. The objective
      was to study, by real time reverse-transcriptase-polymerase chain reaction (RT
      PCR), the effects of postnatal exposure to a reconstituted mixture of AhR
      agonists present in breast milk (3 non-ortho PCBs, 6 PCDDs, and 7 PCDFs, referred
      to here-in-after as AhRM) on mRNA expression of estrogen receptor (ERalpha),
      enzymes involved with the metabolism of estrogens [catechol-o-methyltransferase
      (Comt), cytochrome P450 (Cyp)1A1, 1B1 and 2B1], and DNA methyltransferase-1
      (Dnmt1), in brain areas, liver and uterus of immature female rats. Neonates were
      exposed by gavage during postnatal day (PND) 1-20 with dosages equivalent to 1,
      10, 100, and 1000 times the estimated average human exposure level, and were
      sacrificed at PND 21. None of the end points were affected in uterine cross
      sections, or in samples of uterine tissue layers collected by laser capture
      microdissection. At 1000x, the AhRM reduced Dnmt1 mRNA abundance to 28% and 32%
      of control in the liver and hypothalamus, respectively. In the brain, Cyp1A1 was
      increased (409%) but ERalpha was reduced (66%). Similarly, mRNA abundance for
      Comt isoforms was reduced in the liver (45%) and brain areas (55-70%). AhRM at
      100x, the lowest effective dose, exerted a 220% increase in brain cortex Comt
      [membrane bound (Mb)], a 219% increase in hepatic Cyp1B1, and a 63% decrease in
      hepatic Comt (soluble (S)+Mb). These results support the possibility that early
      exposure to environmental contaminants could lead to effects mediated by changes
      in DNA methylation and/or estrogen metabolism and signaling.

PMID- 15858228
TI  - Directed binding: a novel physical mechanism that describes the directional
      motion of two-headed kinesin motor proteins.
AB  - We propose a novel physical mechanism to describe the mode of processive
      propagation of two-headed kinesin motor proteins along microtubule (MT)
      filaments. Binding and unbinding of the kinesin heads to and from the MT filament
      play a crucial role in producing movement. The chemical energy of adenosine
      triphosphate hydrolysis is used in large part for the unbinding process of
      kinesin from the MT filament. Importantly, in our model, the binding of each head
      is to be directionally oriented to the MT filament. Therefore, we treat the two
      motor domains (heads) as extended objects that are connected with each other by a
      neck region that contains the kinesin dimerization domain. The head domains
      recognize tubulin binding sites by feeling the two-dimensional periodic potential
      from the MT surface and are also subjected to thermal noise. Using experimentally
      determined results regarding physical parameters of the walk, we develop a simple
      mathematical and mechanical model in which directed binding of the heads to
      tubulin results in a directed twist of the molecule, probably in the neck linker
      region, away from its relaxed state. Unbinding of the head from the filament
      relaxes the twist and defines the propagation direction. We showed that there
      must be at least two torsional springs (one for every head) involved that can
      store elastic energy. Consequently, in our model, it is the internal structure
      both of the relaxed and tensed-up state and the transition mode between them that
      define the walking direction of kinesin. We present calculations based on the
      model that are in good quantitative agreement with experimental observations for
      kinesin.

PMID- 15858229
TI  - Kinetics of allosteric conformational transition of a macromolecule prior to
      ligand binding: analysis of stopped-flow kinetic experiments.
AB  - Two fundamentally different mechanisms of ligand binding are commonly encountered
      in biological kinetics. One mechanism is a sequential multistep reaction in which
      the bimolecular binding step is followed by first-order steps. The other
      mechanism includes the conformational transition of the macromolecule, before the
      ligand binding, followed by the ligand binding process to one of the
      conformational states. In stopped-flow kinetic studies, the reaction mechanism is
      established by examining the behavior of relaxation times and amplitudes as a
      function of the reactant concentrations. A major diagnostic tool for detecting
      the presence of a conformational equilibrium of the macromolecule, before the
      ligand binding, is the decreasing value of one of the reciprocal relaxation times
      with the increasing [ligand]. The sequential mechanism cannot generate this
      behavior for any of the relaxation times. Such dependence is intuitively
      understood on the basis of approximate expressions for the relaxation times that
      can be comprehensively derived, using the characteristic equation of the
      coefficient matrix and polynomial theory. Generally, however, the used
      approximations may not be fulfilled. On the other hand, the two kinetic
      mechanisms can always be distinguished, using the approach based on the combined
      application of pseudo-first-order conditions, with respect to the ligand and the
      macromolecule. The two experimental conditions differ profoundly in the extent of
      the effect of the ligand on the protein conformational equilibrium. In a large
      excess of the ligand, the conformational equilibrium of the macromolecule, before
      the ligand binding, is strongly affected by the binding process. However, in a
      large excess of the macromolecule, ligand binding does not perturb the internal
      equilibrium of the macromolecule. As a result, the normal mode, affected by the
      conformational transition, is absent in the observed relaxation process. In the
      case of a sequential mechanism, the number of relaxation times is not altered by
      different pseudo-first-order conditions. Thus, the approach provides a strong
      diagnostic criterion for detecting the presence of the conformational transition
      of the macromolecule and establishing the correct mechanism. Application of this
      approach is illustrated for the binding of 3'-O-(N-methylantraniloyl)-5'
      diphosphate to the E. coli DnaC protein.

PMID- 15858230
TI  - On the analysis of large-scale genomic structures.
AB  - We apply methods from statistical physics (histograms, correlation functions,
      fractal dimensions, and singularity spectra) to characterize large-scale
      structure of the distribution of nucleotides along genomic sequences. We discuss
      the role of the extension of noncoding segments ("junk DNA") for the genomic
      organization, and the connection between the coding segment distribution and the
      high-eukaryotic chromatin condensation. The following sequences taken from
      GenBank were analyzed: complete genome of Xanthomonas campestri, complete genome
      of yeast, chromosome V of Caenorhabditis elegans, and human chromosome XVII
      around gene BRCA1. The results are compared with the random and periodic
      sequences and those generated by simple and generalized fractal Cantor sets.

PMID- 15858231
TI  - Molecular determinants of voltage-gated potassium currents in vascular smooth
      muscle.
AB  - Voltage-gated K+ channels (Kv) play an important role in regulating contraction
      of vascular smooth muscle cells (VSMC) through their effects on membrane
      potential and on voltage-gated Ca2+ channel activity. Kv channels are tetrameric
      structures consisting of four identical or closely related pore-forming alpha
      subunits that may be associated with accessory subunits. More than 30 different
      gene products that contribute to Kv channel complexes have been identified to
      date, some of which are subject to alternative splicing. Consequently, there is
      an enormous potential diversity in the molecular composition and properties of
      possible Kv channel complexes. Electrophysiologic measurements of K+ currents in
      VSMC suggest the presence of multiple Kv channel assemblies including: (1)
      rapidly inactivating, 4-aminopyridine-sensitive, (2) slowly inactivating,
      tetraethylammonium-insensitive, and (3) noninactivating, tetraethylammonium
      sensitive components. Based on electro physiological and expression studies, it
      is likely that the latter two components are represented by a heteromultimeric
      complex of Kv1.2 with either Kv1.4 or Kv1.5 and a Kvbeta1 subunit, and by at
      least Kv2.1, respectively. The identity of the first A-type current component,
      however, is not clear at this time. The relative abundance of these current
      components appears to vary in VSMC from different anatomical sites, from animals
      of different ages, and perhaps in VSMC within specific vascular segments.
      Expression of numerous Kv alpha and beta subunits has been demonstrated in VSMC
      at both the gene and protein level. However, the number of expressed subunits
      appears to be much larger than the number of apparent Kv current components. It
      remains unclear if all of these transcripts are expressed in VSMC or in other
      cell types in the tissue, or if expression patterns are homogenous or
      heterogeneous in VSMC at a given site.

PMID- 15858232
TI  - Toward a molecular understanding of the structure-function of ryanodine receptor
      Ca2+ release channels: perspectives from recombinant expression systems.
AB  - Identification of the genetic basis of human diseases linked to dysfunctional
      free calcium (Ca2+) signaling has triggered an explosion of interest in the
      functional characterization of the molecular components regulating intracellular
      Ca2+ homeostasis. There is a growing appreciation of the central role of
      intracellular ryanodine-sensitive Ca2+ release channel (RyR) regulation in
      skeletal and cardiac muscle pathologies, including malignant hyperthermia, heart
      failure, and sudden cardiac death. The use of cloned RyR isoforms and recombinant
      expression techniques has greatly facilitated the elucidation of the molecular
      basis of RyR Ca2+ release functionality. This review will focus on the
      recombinant techniques used in the functional characterization of recombinant RyR
      isoforms and the insights that these approaches have yielded in unraveling the
      mechanistic basis of RyR channel functionality.

PMID- 15858233
TI  - Industrial scale-up of pH-controlled liquid hot water pretreatment of corn fiber
      for fuel ethanol production.
AB  - The pretreatment of cellulose in corn fiber by liquid hot water at 160 degrees C
      and a pH above 4.0 dissolved 50% of the fiber in 20 min. The pretreatment also
      enabled the subsequent complete enzymatic hydrolysis of the remaining
      polysaccharides to monosaccharides. The carbohydrates dissolved by the
      pretreatment were 80% soluble oligosaccharides and 20% monosaccharides with <1%
      of the carbohydrates lost to degradation products. Only a minimal amount of
      protein was dissolved, thus enriching the protein content of the undissolved
      material. Replication of laboratory results in an industrial trial at 43 gallons
      per minute (163 L/min) of fiber slurry with a residence time of 20 min
      illustrates the utility and practicality of this approach for pretreating corn
      fiber. The added costs owing to pretreatment, fiber, and hydrolysis are
      equivalent to less than 0.84 dollars/gal of ethanol produced from the fiber.
      Minimizing monosaccharide formation during pretreatment minimized the formation
      of degradation products; hence, the resulting sugars were readily fermentable to
      ethanol by the recombinant hexose and by pentose-fermenting Saccharomyces
      cerevisiae 424A(LNH-ST) and ethanologenic Escherichia coli at yields >90% of
      theoretical based on the starting fiber. This cooperative effort and first
      successful trial opens the door for examining the robustness of the pretreatment
      system under extended run conditions as well as pretreatment of other cellulose
      containing materials using water at controlled pH.

PMID- 15858234
TI  - Purification and characterization of two low molecular weight endoglucanases
      produced by Penicillium occitanis mutant Pol 6.
AB  - Two endoglucanases (EGs), EG A and EG B, were purified to homogeneity from
      Penicillium occitanis mutant Pol 6 culture medium. The molecular weights of EG A
      and EG B were 31,000 and 28,000 kDa, respectively. The pI was about 3 for EG A
      and 7.5 for EG B. Optimal activity was obtained at pH 3.5 for both
      endoglucanases. Optimal temperature for enzyme activity was 60 degrees C for EG A
      and 50 degrees C for EG B. EG A was thermostable at 60 degrees C and remained
      active after 1 h at 70 degrees C. EGs hydrolyzed carboxymethylcellulose,
      phosphoric acid swollen cellulose, and beta-glucan efficiently, whereas
      microcrystalline cellulose (Avicel) and laminarin were poorly hydrolyzed. Only EG
      B showed xylanase activity. Furthermore, these EGs were insensitive to the action
      of glucose and cellobiose but were inhibited by the divalent cations Hg2+, Co2+,
      and Mn2+.

PMID- 15858235
TI  - Stimulation of Erwinia sp. fumarase and aspartase synthesis by changing medium
      components.
AB  - The optimal concentrations of nutrient medium components, aeration conditions,
      and pH providing for maximum biomass yields, as well as fumarase and L-aspartase
      activities, during submerged cultivation of Erwinia sp. were determined. The data
      showed that different concentrations of carbon source (molasses) and pH of the
      nutrient medium were required to reach the maximum fumarase and L-aspartase
      activities. Calculations performed by application of the additive lattice model
      suggested that the combination of these optimized factors would result in 3.2-,
      3.4-, and 3.8-fold increases as compared to the experimental means in Erwinia sp.
      biomass, and L-aspartase and fumarase activities, respectively. The conditions of
      the fumaric acid biotransformations into L-malic and L-aspartic acids were
      optimized on the basis of intact Erwinia sp. cells, a fumarase and L-aspartase
      producer. In the cases of fumarate transformation into L-malic acid and of
      fumarate transformation into L-aspartic acids, fumarase and L-aspartase
      activities increased 1.5- and 1.7-fold, respectively. The experimental data were
      consistent with these estimates to 80% accuracy. In comparison with the additive
      lattice model, the application of polynomial nonlinear model allowed the between
      factor relations to be considered and analyzed, which resulted in 1.1-, 1.27-,
      and 1.1-fold increases in Erwinia sp. biomass and fumarase and L-aspartase
      activities for the case of cultivation. In the case of fumarate transformation
      into L-malic acid, this model demonstrated a 1.7-fold increase in fumarase
      activity, whereas during fumarate transformation into L-aspartic acid no
      significant change in aspartase activity was observed.

PMID- 15858236
TI  - Purification of glutathione reductase from chicken liver and investigation of
      kinetic properties.
AB  - Glutathione reductase was purified from chicken liver and some characteristics of
      the enzyme were investigated. The purification procedure was composed of four
      steps: preparation of homogenate, ammonium sulfate precipitation, 2',5'-ADP
      Sepharose 4B affinity chromatography, and Sephadex G-200 gel filtration
      chromatography. Owing to the four consecutive procedures, the enzyme was purified
      1714-fold, with a yield of 38%. Specific activity at the final step was 120
      enzyme unit (EU)/mg of protein. The purified enzyme showed a single band on
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The
      molecular weight of the enzyme was found to be 100 kDa by Sephadex G-200 gel
      filtration chromatography, and the subunit molecular weight was found to be 43
      kDa by SDS-PAGE. Optimum pH, stable pH, optimum ionic strength, and optimum
      temperature were 7.0, 7.4, 0.75 M Tris-HCl buffer including 1 mM EDTA, and 50
      degrees C, respectively. KM and Vmax values for NADPH and glutathione disulfide
      (GSSG) substrates were also determined for the enzyme.

PMID- 15858237
TI  - Purification and partial characterization of a lipase from Bacillus coagulans
      ZJU318.
AB  - An extracellular lipase was purified from the fermentation broth of Bacillus
      coagulans ZJU318 by CM-Sepharose chromatography, followed by Sephacryl S-200
      chromatography. The lipase was purified 14.7-fold with 18% recovery and a
      specific activity of 141.1 U/mg. The molecular weight of the homogeneous enzyme
      was (32 kDa), determined by sodium dodecyl sulfate (SDS) polyacrylamide gel
      electrophoresis. The enzyme activity was maximum at pH 9.0 and was stable over a
      pH range of 7.0-10.0, and the optimum temperature for the enzyme reaction was 45
      degrees C. Little activity loss (6.2%) was observed after 1 h of incubation at 40
      degrees C. However, the stability of the lipase decreased sharply at 50 and 60
      degrees C. The enzyme activity was strongly inhibited by Ag+ and Cu2+, whereas
      EDTA caused no inhibition. SDS, Brij 30, and Tween-80 inhibited lipase, whereas
      Triton X-100 did not significantly inhibit lipase activity.

PMID- 15858238
TI  - [Prenatal diagnosis of spinal muscular atrophy (SMA) -- indications,
      restrictions, interpretation of results].
AB  - INTRODUCTION: Proximal spinal muscular atrophy of childhood and adolescence (SMA)
      is a genetic autosomal recessive disease. Caused in 96.5% by deletion in the SMN1
      gene. Owing to the homogeneity of the molecular defect. Secondary prophylaxis can
      readily be offered to families at risk of SMA. PATIENTS: Prenatal diagnosis of
      SMA was carried out in a group of 50 families. Which were divided into two
      subgroups: with high and relatively low genetic risk of SMA. In all, 55 prenatal
      tests were performed in the period 1998-2003. RESULTS: In the first group
      including 45 families at high genetic risk, 9 of the 50 tests were positive
      (18%). The diagnosis of SMA was tentative in 7 cases from this group and it was
      based only on the clinical picture (the affected children are not alive,
      therefore DNA samples are not available). Prenatal examination in 1 of these 7
      families showed the SMA genotype. In the second subgroup including 5 families
      with relatively low genetic risk of SMA in none of the studies was there a
      biallelic deletion of exon 7 in the SMNI gene. Mainly parents of children with a
      severe form of SMA and having no healthy offspring asked for prenatal examination
      (73% of the families). CONCLUSIONS: Prenatal diagnosis could be offered to
      families even if the diagnosis of SMA was not genetically verified. The negative
      result should he then interpreted individually. Until the carrier test will not
      he introduced to routine procedures. prenatal diagnosis can be also offered to
      families at relatively low risk of SMA.

PMID- 15858239
TI  - [The role of ret gene in the pathogenesis of Hirschsprung disease].
AB  - Hirschsprung disease is a congenital disorder with the incidence of 1 per 5000
      live births, characterized by the absence of intestinal ganglion cells. In the
      etiology of Hirschsprung disease various genes play a role; these are: RET,
      EDNRB, GDNF, EDN3 and SOX10, NTN3, ECE1, Mutations in these genes may result in
      dominant, recessive or multifactorial patterns of inheritance. Diverse models of
      inheritance, co-existence of numerous genetic disorders and detection of numerous
      chromosomal aberrations together with involvement of various genes confirm the
      genetic heterogeneity of Hirschsprung disease. Hirschsprung disease might well
      serve as a model for many complex disorders in which the search for responsible
      genes has only just been initiated. It seems that the most important role in its
      genetic etiology plays the RET gene, which is involved in the etiology of at
      least four diseases. This review focuses on recent advances of the importance of
      RET gene in the etiology of Hirschsprung disease.

PMID- 15858241
TI  - [Pregnancy complicated by diabetes mellitus].
AB  - Interdisciplinary team work and recommendations of diabetologist and obstetrician
      is the condition of success of antenatal care and consequently perinatal outcome
      in pregnancy complicated by diabetes. Careful insight into the metabolic,
      haemodynamic and vascular disturbances is the basic of contemporary surveillance
      in diabetic pregnancy. The authors emphasise that a diabetic pregnant woman must
      not only pay attention to adequate nutrition and balanced exercise, but also be
      aware of and cope with characteristic, momentary swings in glycemia in order to
      overcome them by appropriate insulin therapy. Continuous supervision for several
      other complications associated with diabetic pregnancy, viz. hypertension,
      retinopathy, thyroid dysfunction, nephropathy and the threat of in utero foetal
      death is justified. Briefly, rigorous measures to sustain normoglycemia and
      normal blood pressure, examination of the retina, thyroid and renal functions as
      well as foetal status evaluation are paramount in appropriate management of major
      common diabetic complications in pregnancy.

PMID- 15858240
TI  - [Molecular-genetic aspects of congenital hypothyroidism].
AB  - Congenital hypothyroidism manifests a complex of symptoms caused by a total lack
      or significant deficiency of thyroxine (T4) and triiodothyronine (T3) in foetal
      life and in the first years of child's life. The incidence of congenital
      hypothyroidism is 1 per 3000-4000 newborns in the world and l per 4800 in Poland.
      There are two main causes of congenital hypothyroidism: defects of thyroid
      development (about 90%), defects of thyroid hormones biosynthesis (~10%), and the
      more seldom occurring defects of the TBG proteins (thyroxine binding globulin) or
      resistance. syndrome to thyroid hormones. Defects of thyroid gland development
      include ectopia, hypoplasia or complete lack of the thyroid (athyreosis). These
      defects are caused by immunological, factors, drugs as well as genetic factors
      such as: TSH receptor gene or thyroid transcription factors: PAX 8. TTF l, TTF 2,
      Pit 1, Prop 1. Defects of thyroid hormones biosynthesis are inherited as
      autosomal recessive. There are 5 main defects of thyroid hormones biosynthesis:
      iodide transport (mutation of hNIS gene), iodine oxygenation (mutation of TPO,
      THOX, PDS genes), the iodination of the tyrosine of thyroglobulin and their
      conjunction (the mutation of TPO TG, PDS genes), the hydrolysis of the T3 and T4
      as well as deiodination. Searching molecular-genetic basis of congenital
      hypothyroidism may improve its diagnostics, make possible to introduce genetic
      examination among patients with congenital hypothyroidism and their family
      members and may make gene therapy possible in the future.

PMID- 15858242
TI  - [Postpartum maternal plasma leptin levels and their relationship to gestational
      diabetes mellitus].
AB  - Leptin is a protein hormone mainly produced by the adipocytes. Apart from its
      autocrine role within the placenta in humans, plasma circulating leptin
      contributes to the endocrine function. Leptin levels may serve as an index of
      metabolic and energy balance in pregnancy. Recent reports have shown a positive
      correlation between leptin concentrations and plasma levels of glycated
      haemoglobin (HbA(1c)) in patients with gestational diabetes mellitus (GDM).
      OBJECTIVES: The aim of the present study was to evaluate leptin levels after
      delivery in GDM and normal glucose tolerance (NGT) women. MATERIALS AND METHODS:
      Plasma leptin concentration and insulin, c-peptide and glycated haemoglobin were
      measured in both. NGT women and in patients with a history of GDM in all patients
      total LDL - and HDL cholesterol concentrations were estimated. We also calculated
      the anthropometric parameters of the mother and birth weight in both groups.
      RESULTS: The plasma leptin concentration after delivery was not different in
      patients with GDM in comparison with the NGT individuals. CONCLUSIONS: We
      concluded that in patients with GDM and normal BM1 the postpartum leptin level
      was not different in comparison with the NGT patients.

PMID- 15858243
TI  - [Autoimmunological basis of gestational diabetes mellitus].
AB  - This paper is a review of recent reports on autoimmune aspects of gestational
      diabetes mellitus (GDM). In a subgroup of GDM patients distinct phenotypic and
      genotypic features could be distinguished. Islet autoantibodies with variable
      frequency are present in samples of sera taken from women with GDM. Beta-cell
      destruction may follow different time course patterns. For this reasons GDM
      patients may develop variable forms of autoimmune DM. We believe that women who
      experienced autoimmune GDM are at risk of type l DM and simultaneously, they are
      candidates for possible immunomodulatory preventive therapy in the future.

PMID- 15858244
TI  - [Perinatal complications in newborns of mothers with gestational diabetes].
AB  - OBJECTIVE: To determine how metabolic monitoring of women with gestational
      diabetes influences the morbidity of newborns. DESIGN: Retrospective study.
      PATIENTS: 352 newborns of mothers with gestational diabetes. 295 mothers suffered
      from diabetes class G1 (G1DM) and 57 from diabetes class G2 (G2DM). MATERIAL AND
      METHODS: Glycated haemoglobin levels measured at the moment of the diagnosis of
      gestational diabetes and shortly before delivery were higher in women with
      diabetes type G2, but the difference was statistically significant only at the
      first measurement (G1 6.1+/-1,5% vs. G2 6.7+/- 1.6%, p<0.01). Mean gestational
      age at the time of delivery in the whole group was 38 +/- 2 hbd and there was not
      any difference between newborns of mothers with G1DM and G2DM. Mean birth weight
      in newborns of G1DM mothers was 3390 +/- 620 g and in newborns ofG2DM mothers it
      was 3330 +/- 720 g (NS). RESULTS: 31 (8.8%) infants were large for gestational
      age (LGA) and 20 (5.7%) infants were small for gestational age (SGA). There was
      not any difference between newborns of mothers with diabetes class G1 and G2 in
      the incidence of LGA and SGA. Neither there was any difference between these two
      groups in the incidence of metabolic disorders (hypoglycemia, hypocalcaemia.
      hypomagnesaemia. hyperbilirubinemia) and other pathologic conditions (respiratory
      distress syndrome (RDS), polycythemia, hypertrophic cardiomyopathy and perinatal
      infections). The incidence of congenital malformations was similar in both
      groups. LGA newborns were statistically more often newborns of mothers with HbA1c
      level exceeding the normal value (HbA1c>6.3%). This correlation was observed both
      in the first measurement of HbA l c and the measurement performed shortly before
      delivery. In LGA newborns we observed hypoglycemia, polycythemia and hypertrophic
      cardiomyopathy more often. Perinatal infections appeared statistically more often
      in the SGA newborns. 31.25% infants from the study group were born before the end
      of the 37th week of gestation. These newborns more often suffered from RDS,
      hypoglycemia, hyperbilirubinemia and perinatal infections. CONCLUSION: There was
      not any significant difference in neonatal outcome in newborns of mothers with
      gestational diabetes class G1 and G2. This might have resulted from the fact that
      there was neither any statistically significant difference between these two
      groups in HbA1c level measured shortly before delivery. The incidence of
      metabolic disorders in newborns was correlated with LGA, SGA and prematurity, but
      there was not any difference in the occurrence of metabolic disorders between
      newborns of mothers with G1DM and G2DM.

PMID- 15858245
TI  - [Human papillomavirus -- the major infectious factor in the process of cervical
      intraepithelial neoplasia].
AB  - In spite of increasing knowledge concerning cervical cancer; and the documented
      role of Human Papilloma Virus (HPV) -- as a major causing factor; there have been
      no changes in the epidemiological situation of this disease, especially in our
      country. Cytological screening has made crucial impact on decreasing mortality in
      that carcinoma. HPV involvement in cervical neoplasia and new diagnostic methods
      give possibility for early diagnosis of cervical lesions and to identify the
      group of women with higher risk of cervical cancer. Nevertheless there are no
      strict recommendations concerning HPV diagnostic procedures especially in the
      mass screening programmes. Therapeutic methods, specifically for HPV infection
      are still unknown. Based on the above, questions arise, if it is medically and
      financially justifiable to detect HPV infection? What is the clinical algorithm
      for the management of infected patient? And what is the future treatment?

PMID- 15858246
TI  - [Congenital duodenal obstruction -- Part I].
AB  - Congenital duodenal obstruction is a cause of 40% of congenital intestinal
      obstructions in newborns. In the first part of this study authors describe the
      etiology, types of this anomaly, clinical symptoms, diagnostic investigation,
      surgical treatment and problems in postoperative management in the newborns
      suffering from congenital duodenal obstruction.

PMID- 15858247
TI  - [Congenital duodenal obstruction - part II].
AB  - THE AIM of the second part of the study was an evaluation of the treatment in
      newborns with congenital duodenal obstruction. MATERIAL AND METHODS: In the years
      1992-2002 in the Department of Paediatric Surgery at the institute of Mother and
      Child in Warsaw, 601 newborns with congenital anomalies requiring early surgical
      intervention were treated. Congenital duodenal obstruction was diagnosed in 35
      neonates with birth weight from 800 g to 3450 g. Thirty three patients were
      operated. Ten of them had associated anomalies of the cardiovascular system,
      gastro-intestinal and urinary tracts. Additionally, in three of them genetic
      disorders were suspected. Treatment of all 35 newborns was analysed in order to
      identify factors influencing prognosis in babies with congenital duodenal
      obstruction. RESULTS: Twenty-five patients survived (72%), ten patients died
      (28%). There were not any surgical complications. Two premature infants had died
      before operative repair, eight neonates after it (8-32 day). Six of them were
      premature babies with respiratory problems and in three of them genetic disorders
      were confirmed: Down's syndrome, Cornelia di Lange syndrome and aberration of the
      fourth and seventh pair of chromosomes. Additionally in six of them serious
      intrauterine infection was diagnosed. Mortality rate considerably decreased in
      the last five years, seven deaths occurred between 1992 and 1997 and only one
      after this time. CONCLUSION: Two groups of risk factors had influence for
      prognosis in neonates with congenital duodenal obstruction and they were not
      connected with operative procedures. Associated genetic disorder were the first
      group of serious risk factors having influence on prognosis, independently of
      surgical disease. On the other hand prematurity with severe respiratory problems
      and coexisting intrauterine infection were the most important prognostic factors
      in survival. Progress in prenatal diagnosis and neonatal intensive care had
      fundamental influence for improvement of results in the last 5 years.

PMID- 15858248
TI  - [Distraction osteogenesis in the treatment of hemifacial microsomia].
AB  - PURPOSE: This report presents the results of distraction osteogenesis using an
      extra oral device in 28 patients with different grade of vertical mandibular
      ramus hypoplasia. MATERIAL AND METHOD: 28 patients (aged 2 to 15 years) with
      hemifacial microsomia underwent unilateral lengthening of the ascending ramus
      using unidirectional extraoral devices (Molina distractor). 3D-CT and
      cephalometric radiographs were analysed to determine the placement of the
      mandibular osteotomy and select the appropriate placement of the distraction
      device. RESULT: On the basis of one-year follow-up we can conclude that
      excellent, stable and functional mandibular lengthening was achieved with
      external distraction osteogenesis with minimal complications in all our patients.
      Coordinated growth between maxillary and mandibular arches with stable occlusion
      is observed. CONCLUSION: Mandibular distraction osteogenesis has proved to be an
      excellent technique for the treatment of mandibular deficiency. Careful and
      comprehensive planning of treatment, coupled with control of the distraction
      vector can bring about predictable results with minimal morbidity. Nevertheless.
      It is our conclusion that good and effective orthodontics within the period of
      consolidation is the key to achieve satisfactory stability results.

PMID- 15858249
TI  - [Facial developmental irregularities of the face- in children with Binder's
      syndrome with regard to indirect angular measurements].
AB  - Binder's syndrome is a disorder characterised by the underdevelopment of maxilla
      and nose. PURPOSE: The paper presents an attempt to analyse the developmental
      irregularities, described by angular features in patients with the syndrome.
      PATIENTS AND METHODS: The research was performed on 4 children aged 5-12 with
      maxillonasal dysplasia. Before orthodontic and surgical treatment standardised
      photographs of the head -- anterior and lateral (right and left) were taken.
      Seven angular measurements were taken on the standardised lateral photographs.
      The same measurements were made in the group of 30 girls and 60 boys aged 5-12
      years. THE RESULTS of measurements were normalized into means and standard
      deviation of analogous features for normal persons in groups of sex and age, then
      every angle of the face was counted. From all angular features, three (fronto
      nasal angle, inclination of upper lip angle and inclination of chin angle) were
      characterised by higher means in children with maxillonasal dysplasia. The most
      favourable mean of normalised value referred to the fronto-nasal angle and was
      2.9. CONCLUSIONS: On the basis of this analysis it was affirmed that people with
      Binder's syndrome are characterised by a flat nose and strong inclination of
      upper lip and chin, resulting in characteristic concave facial profile. The most
      visible malformations of the face concern the inclination of the nose. The
      smallest deviation is localised in the area of the nose and lips.

PMID- 15858250
TI  - [Increasing flow parameters and bladder capacity and its implication in maturing
      of lower urinary tract].
AB  - THE AIM of the study was to estimate changes in urethral flow parameters and
      bladder capacity in children. MATERIAL AND METHODS: Parents of 1055 children in
      the range of age 6-14 years were asked to fill a provided questionnaire. Parents
      of 466 children answered and agreed to have their child investigated. On the base
      of the questionnaire 103 children were excluded. Because of technical problems 33
      children did not undergo the investigation. Voided volume less than 100 ml
      excluded farther 42 children. Uroflowmetric study was performed by means of
      Dantrec flowmeter (Urodyn 1000). Residual volume was assessed by means of
      ultrasonography. The results of 288 volunteers were analysed statistically (149
      boys and 139 girls). Mean age was 10 yrs SD -- 2 yrs. RESULTS: Voided volume and
      flow parameters were higher in girls. Although voided volume and flow parameters
      increased and voiding time decreased in relation to age, only the differences in
      average and maximal flow were found to be significant (p< 0.05). CONCLUSION: The
      goal in development of lower urinary tract is to achieve the possibility to empty
      the bladder effectively. For this purpose increasing flow parameters seem to be
      most important.

PMID- 15858251
TI  - [Effect of cardiopulmonary bypass on selected neutrophil functions in children
      with cyanotic congenital heart disease].
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) is known to induce several pathogenic
      responses in cardiovascular surgery. Children suffering from cyanotic congenital
      heart disease (CCHD) have been assumed to have a deficiency in their defence
      mechanisms. The preoperative clinical condition (hypoxemia and circulation
      disorders) could initiate post CPB inflammatory response. The nature of the
      participation of neutrophils and its time course in the post CPB inflammatory
      response, however, is less clear. THE AIM of our study was to investigate
      alterations in expression of adhesion molecules and L-selectin on neutrophils,
      and soluble adhesion molecules levels in CCHD children. MATERIALS AND METHODS: 23
      infants and children with congenital heart disease, scheduled for primary
      corrective surgical repair; were enrolled. Expression of CD11b. CD18, and CD62L
      on neutrophils was determined by cytometry. Additionally, serum concentrations of
      soluble ELAM-1, L-selectin were measured using enzyme-linked immunoassay. Blood
      samples of children with CCHD were collected at the following times: before
      anaesthesia, at the initiation of CPB, after 30 minutes of CPB, at the end of
      CPB, and 24 hours and 72 hours after surgery. RESULTS: The expression of CD11b
      molecule on neutrophils was increased significantly at the start of CPB and
      returned to the baseline after 24 hrs. In all patients, preoperative CD11b
      expression on neutrophils correlated with hypoxemia. Reduced CD62L expression on
      neutrophils and soluble L-selectin concentration were observed at the end of CPB.
      CONCLUSION: We conclude, that cardiac surgery with CPB has a suppressive effect
      on adhesion molecules expression in children with CCHD, These findings also
      suggest that the type of neutrophil response to cardiac surgery appears to depend
      on preoperative clinical condition.

PMID- 15858252
TI  - [Current views on the etiopathogenesis of idiopathic osteoporosis and osteopenia
      in the developmental period].
AB  - The paper presents current literature review on the clinical features and
      possible etiopathogenetic factors in idiopathic osteoporosis and osteopenia in
      children and adolescents. Genetic and environmental factors determining bone mass
      growth are included. The effect of cytokines and hormones in the regulation of
      bone remodelling has been discussed in detail. Most recent studies have
      demonstrated that cytokines are involved in bone formation and resorption by
      their direct influence on the activity of osteoclasts and osteoblasts. In this
      way they affect the state of dynamic balance between the process of bone
      formation and resorption, and thus the mineralization of the skeleton.

PMID- 15858253
TI  - [Carbohydrate and lipid metabolism disorders in obese children and adolescents].
AB  - THE AIM of the study was to assess the incidence of: 1. insulin resistance,
      hyperinsulinemia, impaired glucose tolerance and dyslipoproteinemia in serum of
      obese children according to the type of obesity; 2. family history of obesity,
      hypertension and type 2 diabetes mellitus. MATERIAL AND METHODS: 177 obese
      children (M/F 80/97) aged 10-17.5 yrs and 38 normostenic children (control group)
      were screened for carbohydrate and lipid metabolism disorders. BMI (> or =97 c)
      and WHR (M/F> or =0.9/0.85 -- abdominal adiposity) were estimated. Glycemia
      (mmol/l) and insulinemia (microIU/ml) at 0, 30, 60, 90, 120 minutes of OGTT were
      measured. Fasting C-peptide (ng/ml), HbAlc (%). total cholesterol, LDL-Ch, HDL
      Ch, triglycerides (mmol/l), I/G ratio (microIU/ml/mg%) and ChT/HDL-Ch atherogenic
      index were also investigated. RESULTS: Abdominal adiposity was present in 56.5%.
      fasting hyperinsulinemia (>20.0 microIU/ml) in 32.2%, insulin resistance
      (I/G>0.30) in 73.7%; in the group of patients with hyperinsulinemia 66.7% had
      abdominal adiposity. The glycemia ill OGTT was: normal in 57.0% -- group I; 26.6%
      did not suit the criteria of normal nor impaired glucose tolerance according to
      American Diabetes Association (ADA) -- group Ia. The impaired glucose tolerance
      (IGT) was found in 16.4% -- group II, with fasting hyperinsulinemia in 58.6% and
      I/G ratio > or =0.30 in 41.3%, HbAlc > 6.2% in 34.5%. Atherogenic lipoproteins
      levels prevailed (p<0.05) in group Ia and II. The incidence of family history of
      obesity, hypertension and diabetes mellitus type 2 was higher (statistically not
      significant, p>0.05) in group Ia and II and significantly higher (p<0.05) in all
      groups of obese children compared to the control group. CONCLUSION: The results
      of our study prove that obesity in children is a risk factor for early diabetes
      mellitus type 2 and atherosclerosis.

PMID- 15858254
TI  - [Lymphocytes T gammadelta receptors in hypertrophied adenoids in children with
      otitis media with effusion].
AB  - BACKGROUND: The pharyngeal tonsil is the place of immunological system first
      contact with pathogenic factors in the nasopharyngeal region, which is
      responsible for local defence from infection. Chronic antigenic stimulation can
      lead to adenoid dysfunction and hypertrophy (PMG). Significant role in PMG and in
      the otitis media with effusion (WZU) play lymphocytes T (CD3(+)) and T-TCR
      gammadelta. THE AIM of the study was a quantitative analysis of lymphocytes T
      (CD3(+)) and T-TCR gammadelta in adenoid hypertrophy and otitis media with
      effusion lasting more than 3 months. MATERIAL AND METHODS: An investigation was
      executed by flow cytometry in hypertrophied adenoids from children after
      tonsillectomy. The study and control groups were divided in to 2 subgroups:
      children younger than 5 years and those aged from 5 to 17 years. RESULTS: The
      study showed a statistically significant reduction from 35.6+/-3.1% to 32.0+/
      2.8% (p < 0.04) of lymphocytes T gammadelta CD3(+) in the examined group (WZU)
      compared to the control group (PMG). There was a higher percentage of lymphocytes
      with TCR gammadelta receptor expression in children with WZU (2.04+/-1.13%) than
      in PMG group (0.99+/-0.44%) (p < 0.002). The lowest percentage of lymphocytes T
      TCR gammadelta was found in younger children with PMG (0.67+/-0.17%) and the
      highest in WZU in younger children (2.13+/-1.04%) (p < 0.0001). We observed a
      statistically significant difference in expression of TCR receptors (p < 0.02)
      between younger children with PMG (0.67+/-0.17%) and older children with PMG
      (1.24+/-0.43%). We did not find significant differences in lymphocytes T CD3(+)
      related to age. CONCLUSIONS: The enlarged percentage of lymphocytes T gammadelta
      in adenoid hypertrophy in children with WZU create a possibility of a more rapid
      response to inflammatory factors.

PMID- 15858255
TI  - [Diagnostic and therapeutic management of essential thrombocythemia in children].
AB  - BACKGROUND: Essential thrombocythemia is a myeloproliferative disease resulting
      from the clonal proliferation of a multipotent myeloid stem cell with an
      increased platelet count in peripheral blood. In 2% of cases the cause remains
      unknown. It is then called idiopathic essential thrombocythemia. THE AIM: The
      objective of this study was to present the diagnostic and therapeutic management
      of essential thrombocythemia in children. MATERIAL AND METHODS: The authors
      analysed complete medical records of 5 patients treated for essential
      thrombocythemia in the Department of Children Haematology and Oncology, Medical
      University Lublin during a 6 years (1996-2002) period. The investigated group
      consisted of 5 children: 3 boys and 2 girls with mean age of 7 years and 8 months
      (varying from 5 years and 3 months to 11 years and 8 months). RESULTS: The
      peripheral platelet count was above 1200 x 10(9)/L. Three patients developed
      functional symptoms of microvascular blood flow alteration (headaches, sensory
      disorders. paresthesiae). In 2 patients thrombocythemia was asymptomatic and the
      diagnosis was made incidentally. Diagnosis of essential thrombocythemia was made
      according to the criteria of the Polycythemia Vera Study Group and treatment with
      anagrelide hydrochloride was started. One patient due to bad drug tolerance was
      treated with hydroxyurea. Treatment of essential thrombocythemia in all patients
      resulted in: (1) decreased (500-600 x 10(9)/L) platelet count in peripheral
      blood; (2) resolving the symptoms of small vessels obturation (headaches, sensory
      disorders, paresthesiae); (3) low platelet separating megakaryocytes count in
      control myelograms (4) no transformation into acute neoplastic disease.
      CONCLUSIONS: In the treatment of children with essential thrombocythemia
      anagrelid was effective in four of five patients.

PMID- 15858256
TI  - [Second neoplasm in a 13-year-old boy complicated by Crohn's disease. Case
      report].
AB  - Genetic abnormalities and immune system disorders resulting from them are the
      causes of neoplastic diseases as well as inflammatory bowel disease, including
      Crohn's disease. However, the rearrangement of genes may not only be the cause of
      neoplasms but also the result of oncolytic treatment used. One of the late
      treatment-related complications of neoplastic diseases is the development of a
      second neoplasm and possible disorders belonging to the group of inflammatory
      bowel diseases, for example Crohn's disease. The paper presents the case of a 13
      year-old boy (K.G.) treated for a second neoplasm, complicated by Crohn's
      disease. The patient was diagnosed with acute lymphoblastic leukaemia -- middle
      risk group (ALL-MRG) at the age of 3, treated according to the BFM 87 Protocol
      (dexamethasone, prednisone, vincristine, daunoribicin, asparaginase,
      cyclophosphamide, cytarabine, mercaptopurine, methotrexate, thioguanine,
      doxorubicin), and complete remission was achieved. Eight years after the first
      line treatment the boy was diagnosed with the second neoplastic process -- pre-B
      acute lymphoblastic leukaemia (ALL-L2 pre-B common +). The ALLIC 2002 Protocol
      (dexamethasone, prednisone, vincristine, daunoribicin, asparaginase,
      cyclophosphamide, cytarabine, mercaptopurine. methotrexate, thioguanine,
      doxorubicin) was started. On day 71 of the therapy, during aplasia of blood
      marrow following chemotherapy, inflammation of the caecum was diagnosed and
      metronidazole was introduced. Once blood counts improved, the complaints
      decreased and with continued chemotherapy of Protocol M (mercaptopurine,
      methotrexate), completely subsided. The symptoms reappeared during the 2-week
      break before Protoco II. The physical examination revealed the presence of a
      hard, painless tumour (3 x 10 cm) in the right iliac fossa. Colonoscopy showed a
      cauliflower-like formation within the Mauchin's valve projecting to the caecum
      lumen. The histopathological evaluation of the sections demonstrated a typical
      picture of Crohn's disease. Crohn's disease of the ileum was diagnosed, the
      treatment with dexamethazone (according to Protocol II) was instituted which led
      to complete regression of the iliac lesions. Steroid therapy (prednisone)
      continued until the treatment supporting the remission according to Protocol
      ALLIC 2002 (mercaptopurine, methotrexate orally) was initiated. CONCLUSION: The
      differential diagnosis of complications accompanying neoplasms should consider
      the inflammatory bowel diseases; their atypical course may be masked by the
      treatment of the underlying disease.

PMID- 15858257
TI  - [Single dose of montelukast as an effective prevention of post exercise
      bronchospasm in children with bronchial asthma].
AB  - Post exercise bronchospasm is a well-known phenomenon, particularly affecting
      children with asthma. In our own study post exercise bronchospasm occurred in 25
      66% of children with asthma. The aim of the study was to evaluate the usefulness
      of cysteinyl leukotriene receptor antagonist -- montelukast (Mnt) in the
      prevention of post exercise bronchospasm. MATERIAL AND METHODS: We studied 72
      children 7-14 years old (22 girls, 50 boys) mean age -- 10.8+/- 2.4 (SD), who
      were suffering from asthma. All children with forced expiratory volume in one
      second (FEV1) >70% of the predicted value and a reproducible fall in FEV1 after
      exercise of at least 15% were enrolled. After a screening test was performed the
      children were divided in 2 subgroups: 40 children for active treatment --
      montelukast, 32 for placebo group. Placebo or montelukast (5 mg) was given once
      in the evening, randomised, double blind. Next day 3 bronchial provocation tests
      at 8 a.m., 12 a.m. and 3 p.m. were performed. Data from 72 patients were
      available for complete analysis of the following parameters: forced expiratory
      volume in one second (FEV1), peak expiratory flow (PEF) forced expiratory flow at
      25 and 75 of forced vital capacity (FEF 25-75%). RESULTS: Analysis showed a
      significant total protective effect 12 h after giving montelukast in 25/40
      (62.5%) children, but only in 4/32 (12.5%) in the placebo group, (OR=1.87).
      Partial protection was detected in 3/40 (7.5%) children in montelukast group and
      in 1/32 (3.3%) child in placebo group. Lack of protection was observed in 12/40
      (30%) in montelukast group and in 27/42 (84.4%) in the placebo group.
      CONCLUSIONS: l. The clinically recommended dose of montelukast protects against
      post exercise induced bronchospasm. 2. The time of duration of montelukast as
      protective treatment of post exercise bronchospasm was at least 21 hours. 3. Our
      study may suggest the participation of leukotrienes in the pathogenesis of
      exercise-induced broncho-constriction.

PMID- 15858258
TI  - Structural studies of glucose-6-phosphate and NADP+ binding to human glucose-6
      phosphate dehydrogenase.
AB  - Human glucose-6-phosphate dehydrogenase (G6PD) is NADP(+)-dependent and catalyses
      the first and rate-limiting step of the pentose phosphate shunt. Binary complexes
      of the human deletion mutant, DeltaG6PD, with glucose-6-phosphate and NADP(+)
      have been crystallized and their structures solved to 2.9 and 2.5 A,
      respectively. The structures are compared with the previously determined
      structure of the Canton variant of human G6PD (G6PD(Canton)) in which NADP(+) is
      bound at the structural site. Substrate binding in DeltaG6PD is shown to be very
      similar to that described previously in Leuconostoc mesenteroides G6PD. NADP(+)
      binding at the coenzyme site is seen to be comparable to NADP(+) binding in L.
      mesenteroides G6PD, although some differences arise as a result of sequence
      changes. The tetramer interface varies slightly among the human G6PD complexes,
      suggesting flexibility in the predominantly hydrophilic dimer-dimer interactions.
      In both complexes, Pro172 of the conserved peptide EKPxG is in the cis
      conformation; it is seen to be crucial for close approach of the substrate and
      coenzyme during the enzymatic reaction. Structural NADP(+) binds in a very
      similar way in the DeltaG6PD-NADP(+) complex and in G6PD(Canton), while in the
      substrate complex the structural NADP(+) has low occupancy and the C-terminal
      tail at the structural NADP(+) site is disordered. The implications of possible
      interaction between the structural NADP(+) and G6P are considered.

PMID- 15858259
TI  - The endoproteinase furin contains two essential Ca2+ ions stabilizing its N
      terminus and the unique S1 specificity pocket.
AB  - The mammalian prohormone/proprotein convertase (PC) furin is responsible for the
      maturation of a great variety of homeostatic but also many pathogenic proteins
      within the secretory pathway and the endosomal pathway and at the cell surface.
      Similar to other members of the PC family, furin requires calcium for catalytic
      activity. In a previous paper, the structural association of the catalytic and
      the P-domain of furin was shown and data were presented indicating two or three
      calcium-binding sites. The exact number and the three-dimensional localization of
      the essential calcium sites within furin have now been determined by collecting X
      ray diffraction data on either side of the Ca K absorption edge and by
      calculating a novel type of double difference map from these anomalous scattering
      data. Two calcium ions were unambiguously identified: the purely structural Ca-1
      also conserved in the bacterial digestive subtilisins and the Ca-2 site specific
      to PCs and essential for the formation of the P1 specificity-determining S1
      binding pocket. In addition, these anomalous diffraction data show that no
      tightly bound K(+) sites exist in furin.

PMID- 15858260
TI  - Crystal engineering yields crystals of cyclophilin D diffracting to 1.7 A
      resolution.
AB  - In the pharmaceutical industry, knowledge of the three-dimensional structure of a
      specific target facilitates the drug-discovery process. Despite possessing
      favoured analytical properties such as high purity and monodispersion in light
      scattering, some proteins are not capable of forming crystals suitable for X-ray
      analysis. Cyclophilin D, an isoform of cyclophilin that is expressed in the
      mitochondria, was selected as a drug target for the treatment of cardiac
      disorders. As the wild-type enzyme defied all attempts at crystallization,
      protein engineering on the enzyme surface was performed. The K133I mutant gave
      crystals that diffracted to 1.7 A resolution using in-house X-ray facilities and
      were suitable for soaking experiments. The crystals were very robust and
      diffraction was maintained after soaking in 25% DMSO solution: excellent
      conditions for the rapid analysis of complex structures including
      crystallographic fragment screening.

PMID- 15858261
TI  - Parameter-space screening: a powerful tool for high-throughput crystal structure
      determination.
AB  - The determination of protein structures on a genomic scale requires both
      computing capacity and efficiency increases at many stages along the complex
      process. By combining bioinformatics workflow-management techniques, cluster
      based computing and popular crystallographic structure-determination software
      packages, an efficient and powerful new tool for structural biology/genomics has
      been developed. Using the workflow manager and a simple web interface, the
      researcher can, in a few easy steps, set up hundreds of structure-determination
      jobs, each using a slightly different set of program input parameters, thus
      efficiently screening parameter space for the optimal input-parameter
      combination, i.e. a set of parameters that leads to a successful structure
      determination. Upon completion, results from the programs are harvested,
      analyzed, sorted based on success and presented to the user via the web
      interface. This approach has been applied with success in more than 30 cases.
      Examples of successful structure determinations based on single-wavelength
      scattering (SAS) are described and include cases where the 'rational'
      crystallographer-based selection of input parameters values had failed.

PMID- 15858262
TI  - High-resolution crystal structure of an avidin-related protein: insight into high
      affinity biotin binding and protein stability.
AB  - The chicken avidin gene belongs to an extended gene family encoding seven avidin
      related genes (AVRs), of which only avidin is expressed in the chicken. The
      sequences of AVR4 and AVR5 are identical and the common protein (AVR4) has been
      expressed both in insect and bacterial systems. The recombinant proteins are
      similarly hyperthermostable and bind biotin with similarly high affinities. AVR4
      was crystallized in the apo and biotin-complexed forms and their structures were
      determined at high resolution. Its tertiary and quaternary structures are very
      similar to those of avidin and streptavidin. Its biotin-binding site shows only a
      few alterations compared with those of avidin and streptavidin, which account for
      the observed differences in binding affinities. The increased
      hyperthermostability can be attributed to the conformation of the critical L3,4
      loop and the extensive network of 1-3 inter-monomeric interactions. The loop
      contains a tandem Pro-Gly sequence and an Asp-Arg ion pair that collectively
      induce rigidity, thus maintaining its closed and ordered conformation in both the
      apo and biotin-complexed forms. In addition, Tyr115 is present on the AVR4 1-3
      monomer-monomer interface, which is absent in avidin and streptavidin. The
      interface tyrosine generates inter-monomeric interactions, i.e. a tyrosine
      tyrosine pi-pi interaction and a hydrogen bond with Lys92. The resultant network
      of interactions confers a larger 1-3 dimer-dimer contact surface on AVR4, which
      correlates nicely with its higher thermostability compared with avidin and
      streptavidin. Several of the proposed thermostability-determining factors were
      found to play a role in strengthening the tertiary and quaternary integrity of
      AVR4.

PMID- 15858263
TI  - Production and X-ray crystallographic analysis of fully deuterated cytochrome
      P450cam.
AB  - Neutron protein crystallography allows H-atom positions to be located in
      biological structures at the relatively modest resolution of 1.5-2.0 A. A
      difficulty of this technique arises from the incoherent scattering from hydrogen,
      which considerably reduces the signal-to-noise ratio of the data. This can be
      overcome by preparing fully deuterated samples. Efficient protocols for routine
      and low-cost production of in vivo deuterium-enriched proteins have been
      developed. Here, the overexpression and crystallization of highly (>99%)
      deuterium-enriched cytochrome P450cam for neutron analysis is reported.
      Cytochrome P450cam from Pseudomonas putida catalyses the hydroxylation of camphor
      from haem-bound molecular O(2) via a mechanism that is thought to involve a
      proton-shuttle pathway to the active site. Since H atoms cannot be visualized in
      available X-ray structures, neutron diffraction is being used to determine the
      protonation states and water structure at the active site of the enzyme. Analysis
      of both hydrogenated and perdeuterated P450cam showed no significant changes
      between the X-ray structures determined at 1.4 and 1.7 A, respectively. This work
      demonstrates that the fully deuterated protein is highly isomorphous with the
      native (hydrogenated) protein and is appropriate for neutron protein
      crystallographic analysis.

PMID- 15858264
TI  - High-resolution structure of myo-inositol monophosphatase, the putative target of
      lithium therapy.
AB  - Inositol monophosphatase is a key enzyme of the phosphatidylinositol signalling
      pathway and the putative target of the mood-stabilizing drug lithium. The crystal
      structure of bovine inositol monophosphatase has been determined at 1.4 A
      resolution in complex with the physiological magnesium ion ligands. Three
      magnesium ions are octahedrally coordinated at the active site of each of the two
      subunits of the inositol monophosphatase dimer and a detailed three-metal
      mechanism is proposed. Ligands to the three metals include the side chains of
      Glu70, Asp90, Asp93 and Asp220, the backbone carbonyl group of Ile92 and several
      solvent molecules, including the proposed nucleophilic water molecule (W1)
      ligated by both Mg-1 and Mg-3. Modelling of the phosphate moiety of inositol
      monophosphate to superpose the axial phosphate O atoms onto three active-site
      water molecules orientates the phosphoester bond for in-line attack by the
      nucleophilic water which is activated by Thr95. Modelling of the pentacoordinate
      transition state suggests that the 6-OH group of the inositol moiety stabilizes
      the developing negative charge by hydrogen bonding to a phosphate O atom.
      Modelling of the post-reaction complex suggests a role for a second water
      molecule (W2) ligated by Mg-2 and Asp220 in protonating the departing
      inositolate. This second water molecule is absent in related structures in which
      lithium is bound at site 2, providing a rationale for enzyme inhibition by this
      simple monovalent cation. The higher resolution structural information on the
      active site of inositol monophosphatase will facilitate the design of substrate
      based inhibitors and aid in the development of better therapeutic agents for
      bipolar disorder (manic depression).

PMID- 15858265
TI  - Phasing at resolution higher than the experimental resolution.
AB  - Limited experimental resolution is a unavoidable feature in macromolecular
      crystallography: it may hinder or make difficult the determination of the crystal
      structure. A novel procedure is presented which from an approximate electron
      density map extrapolates the moduli and phases of non-measured reflections beyond
      and behind the experimental resolution limit. Applications to a set of test
      structures show that the extrapolation can be successfully accomplished. As a
      consequence, the phase estimates of the observed reflections are subsequently
      improved and the interpretability of the corresponding electron-density map
      increases. The use of the extrapolated values for the non-measured reflections
      provides additional information for the map, which shows a resolution higher than
      the experimental resolution.

PMID- 15858266
TI  - COHbC and COHbS crystallize in the R2 quaternary state at neutral pH in the
      presence of PEG 4000.
AB  - Human hemoglobin binds oxygen cooperatively and functions as a tetramer composed
      of two identical alphabeta heterodimers. While human hemoglobin is the best
      characterized allosteric protein, the quaternary R (oxygenated or liganded) to T
      (deoxygenated) structural transition remains controversial. The R2 state has been
      postulated to represent either an intermediate or final quaternary state elicited
      by ligand binding. However, the biological relevance of the R2 state has been
      questioned as it has not been observed crystallographically under physiological
      conditions. The high-resolution R2 quaternary structures of human COHbC (betaE6K)
      and COHbS (betaE6V) are reported at neutral pH and low ionic strength using PEG
      4000 as a precipitant. Crystals of COHbC, COHbS and their mixtures are
      isomorphous, indicating that they share the same tertiary and quaternary
      structures. In contrast, oxyHbA or COHbA did not yield crystals at neutral pH
      under similar conditions. Solubility studies and modeling suggest that at neutral
      pH and low ionic strength the beta6 mutant hemoglobins crystallize (betaK6 >
      betaV6) as a result of more favorable lattice contacts.

PMID- 15858267
TI  - Preliminary neutron diffraction studies of Escherichia coli dihydrofolate
      reductase bound to the anticancer drug methotrexate.
AB  - The contribution of H atoms in noncovalent interactions and enzymatic reactions
      underlies virtually all aspects of biology at the molecular level, yet their
      'visualization' is quite difficult. To better understand the catalytic mechanism
      of Escherichia coli dihydrofolate reductase (ecDHFR), a neutron diffraction study
      is under way to directly determine the accurate positions of H atoms within its
      active site. Despite exhaustive investigation of the catalytic mechanism of DHFR,
      controversy persists over the exact pathway associated with proton donation in
      reduction of the substrate, dihydrofolate. As the initial step in a proof-of
      principle experiment which will identify ligand and residue protonation states as
      well as precise solvent structures, a neutron diffraction data set has been
      collected on a 0.3 mm(3) D(2)O-soaked crystal of ecDHFR bound to the anticancer
      drug methotrexate (MTX) using the LADI instrument at ILL. The completeness in
      individual resolution shells dropped to below 50% between 3.11 and 3.48 A and the
      I/sigma(I) in individual shells dropped to below 2 at around 2.46 A. However,
      reflections with I/sigma(I) greater than 2 were observed beyond these limits (as
      far out as 2.2 A). To our knowledge, these crystals possess one of the largest
      primitive unit cells (P6(1), a = b = 92, c = 73 A) and one of the smallest
      crystal volumes so far tested successfully with neutrons.

PMID- 15858268
TI  - Structure of the subtilisin Carlsberg-OMTKY3 complex reveals two different
      ovomucoid conformations.
AB  - One of the most studied protein proteinase inhibitors is the turkey ovomucoid
      third domain, OMTKY3. This inhibitor contains a reactive-site loop (Lys13I
      Arg21I) that binds in a nearly identical manner to all studied serine
      proteinases, regardless of their clan or specificity. The crystal structure of
      OMTKY3 bound to subtilisin Carlsberg (CARL) has been determined. There are two
      complete copies of the complexes in the crystallographic asymmetric unit. Whereas
      the two enzyme molecules are virtually identical [0.16 A root-mean-square
      difference (r.m.s.d.) for 274 C(alpha) atoms], the two inhibitor molecules show
      dramatic differences between one another (r.m.s.d. = 2.4 A for 50 C(alpha)
      atoms). When compared with other proteinase-bound OMTKY3 molecules, these
      inhibitors show even larger differences. This work facilitates a re-evaluation of
      the importance of certain ovomucoid residues in proteinase binding and explains
      why additivity and sequence-based binding-prediction methods fail for the CARL
      OMTKY3 complex.

PMID- 15858269
TI  - The 2.35 A structure of the TenA homolog from Pyrococcus furiosus supports an
      enzymatic function in thiamine metabolism.
AB  - TenA (transcriptional enhancer A) has been proposed to function as a
      transcriptional regulator based on observed changes in gene-expression patterns
      when overexpressed in Bacillus subtilis. However, studies of the distribution of
      proteins involved in thiamine biosynthesis in different fully sequenced genomes
      have suggested that TenA may be an enzyme involved in thiamine biosynthesis, with
      a function related to that of the ThiC protein. The crystal structure of PF1337,
      the TenA homolog from Pyrococcus furiosus, is presented here. The protomer
      comprises a bundle of alpha-helices with a similar tertiary structure and
      topology to that of human heme oxygenase-1, even though there is no significant
      sequence homology. A solvent-sequestered cavity lined by phylogenetically
      conserved residues is found at the core of this bundle in PF1337 and this cavity
      is observed to contain electron density for 4-amino-5-hydroxymethyl-2
      methylpyrimidine phosphate, the product of the ThiC enzyme. In contrast, the
      modestly acidic surface of PF1337 shows minimal levels of sequence conservation
      and a dearth of the basic residues that are typically involved in DNA binding in
      transcription factors. Without significant conservation of its surface
      properties, TenA is unlikely to mediate functionally important protein-protein or
      protein-DNA interactions. Therefore, the crystal structure of PF1337 supports the
      hypothesis that TenA homologs have an indirect effect in altering gene-expression
      patterns and function instead as enzymes involved in thiamine metabolism.

PMID- 15858270
TI  - Structure of Escherichia coli pyridoxine 5'-phosphate oxidase in a tetragonal
      crystal form: insights into the mechanistic pathway of the enzyme.
AB  - Escherichia coli pyridoxine 5'-phosphate oxidase (ePNPOx) catalyzes the terminal
      step in the biosynthesis of pyridoxal 5'-phosphate (PLP) by the FMN oxidation of
      pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP), forming FMNH(2)
      and H(2)O(2). The crystal structure of ePNPOx is reported in a tetragonal unit
      cell at 2.6 A resolution. The three-dimensional fold of this structure is very
      similar to those of the E. coli and human enzymes that crystallized in trigonal
      and monoclinic unit cells. However, unlike the previous structures, the
      tetragonal structure shows major disorder in one of the two subunit domains that
      has opened up both the active site and a putative tunnel. Comparison of these
      structures gives an insight into the mechanistic pathway of PNPOx: from the
      resting enzyme with no substrate bound, to the initial binding of the substrate
      at the active site, to the catalytic stage and to the release of the catalytic
      product from the active site.

PMID- 15858271
TI  - Cryogenic structure of the photosynthetic reaction center of Blastochloris
      viridis in the light and dark.
AB  - The structure of the Blastochloris viridis photosynthetic reaction center has
      been determined at 100 K by flash-freezing crystals. A data set to 2.2 A
      resolution provides a well determined model of the wild-type protein. Of
      particular interest are the position, occupancy and heterogeneity of the Q(B)
      binding site. Data were also collected from a crystal frozen immediately after
      illumination. The data support predominant binding of Q(B) in the proximal
      position in both the neutral and charge-separated states.

PMID- 15858272
TI  - Escherichia coli MltA: MAD phasing and refinement of a tetartohedrally twinned
      protein crystal structure.
AB  - Crystals were grown of a mutant form of the bacterial cell-wall maintenance
      protein MltA that diffracted to 2.15 A resolution. When phasing with molecular
      replacement using the native structure failed, selenium MAD was used to obtain
      initial phases. However, after MAD phasing the crystals were found to be
      tetartohedrally twinned, hampering correct space-group determination and
      refinement. A refinement protocol was designed to take tetartohedral twinning
      into account and was successfully applied to refine the structure. The refinement
      protocol is described and the reasons for the failure of molecular replacement
      and the success of MAD are discussed in terms of the effects of the tetartohedral
      twinning.

PMID- 15858273
TI  - Structure of human thymidylate synthase under low-salt conditions.
AB  - Human thymidylate synthase, a target in cancer chemotherapy, was crystallized
      from PEG 3350 with 30 mM ammonium sulfate (AS) in the crystallization medium. The
      crystals are isomorphous with the high-salt crystals ( approximately 2.0 M AS)
      and the structure has been solved and refined (R = 22.6%, R(free) = 24.3%) at 1.8
      A resolution. The high- and low-AS-concentration structures are quite similar,
      with loop 181-197 is in the inactive conformation. Also, residues 95-106 and 129
      135 (eukaryotic inserts region) show high mobility as assessed by poor electron
      density and high values of crystallographic temperature factors (residues 1-25
      and 108-129 are disordered in both structures). The high mobility of this region
      may reflect the situation at physiological ionic strength. Of the four sulfate
      ions observed bound at 2.0 M AS, only two are present at 30 mM AS. The inactive
      conformation appears to be stabilized by the side chain of Val3 or a leucine
      residue from the disordered regions. The low-salt conditions of these crystals
      should be much more suitable for the study of thymidylate synthase inhibitors,
      especially those that utilize sulfate-binding sites to stabilize the inactive
      conformation of loop 181-197.

PMID- 15858274
TI  - Water molecules in the antibody-antigen interface of the structure of the Fab
      HyHEL-5-lysozyme complex at 1.7 A resolution: comparison with results from
      isothermal titration calorimetry.
AB  - The structure of the complex between hen egg-white lysozyme and the Fab HyHEL-5
      at 2.7 A resolution has previously been reported [Cohen et al. (1996), Acta
      Cryst. D52, 315-326]. With the availability of recombinant Fab, the X-ray
      structure of the complex has been re-evaluated at 1.7 A resolution. The refined
      structure has yielded a detailed picture of the Fab-lysozyme interface, showing
      the high complementarity of the protein surfaces as well as several water
      molecules within the interface that complete the good fit. The model of the full
      complex has improved significantly, yielding an R(work) of 19.5%. With this
      model, the structural results can be compared with the results of isothermal
      titration calorimetry. An attempt has been made to estimate the changes in bound
      waters that accompany complex formation and the difficulties inherent in using
      the crystal structures to provide the information necessary to make this
      calculation are discussed.

PMID- 15858275
TI  - SSEP-2.0: Secondary Structural Elements of Proteins.
AB  - The Secondary Structural Elements of Proteins (SSEP) database is an integrated
      and comprehensive knowledge base for accessing information related to all the
      secondary-structural elements present in non-redundant (25 and 90%) protein
      chains. The new version 2.0 of the database contains 2485 and 8595 protein chains
      from the 25 and 90% non-redundant data sets, respectively. The necessary web
      interfaces have been developed that enable users to visualize the three
      dimensional structure of the secondary-structural element in the client machine
      using the free molecular-visualization program RASMOL. This source is updated at
      regular intervals and can be accessed through the bioinformatics web server at
      the URL http://cluster.physics.iisc.ernet.in/ssep or http://144.16.71.148/ssep/.

PMID- 15858276
TI  - CADB-2.0: Conformation Angles Database.
AB  - The Conformation Angles Data Base (CADB) is a comprehensive, authoritative and
      timely knowledge base with a powerful query engine developed to facilitate the
      retrieval of information related to the conformational angles (main chain and
      side chain) of the amino-acid residues present in non-redundant (both 25 and 90%)
      data sets. The updated version has improved options for determining the
      dependency of the conformation angles of a particular residue upon the flanking
      residues, doublet analysis, triplet analysis and analysis of a particular protein
      structure. It is worth mentioning that for all options a user-friendly and
      convenient Java graphical user interface (GUI) has been provided to display the
      output on the client machine. The database is accessible at the URL
      http://cluster.physics.iisc.ernet.in/cadb/ or http://144.16.71.148/cadb/.

PMID- 15858277
TI  - A preliminary time-of-flight neutron diffraction study on amicyanin from
      Paracoccus denitrificans.
AB  - Crystals of the blue copper protein amicyanin suitable for neutron diffraction
      were grown by the sitting-drop method, followed by repeated macroseeding using
      solutions prepared with D(2)O. Although the crystal sizes were the same, crystals
      grown using solutions made up in H(2)O in the initial stages of macroseeding and
      solutions with D(2)O in later stages did not diffract neutrons well. However,
      when the protein was initially exchanged with buffered D(2)O and then
      crystallized and also macroseeded using solutions made up in D(2)O throughout,
      the crystals diffracted neutrons to high resolution. One of those crystals was
      used to collect a data set to a resolution of 1.9 A.

PMID- 15858278
TI  - Sample preparation and mass-spectrometric characterization of crystal-derived
      protein samples.
AB  - Mass spectrometry is often used to ascertain the accurate mass of purified
      protein samples prior to crystallization screening. However, in many cases data
      regarding the form of the protein crystallizing can also be useful, as this may
      differ from the original sample. Development of a simple method for the
      preparation and mass spectrometry of crystal-derived protein samples is
      described. The method is exemplified by the determination of the phosphorylation
      state of protein in a crystal derived from a mixture of phosphorylated and
      unphosphorylated protein.

PMID- 15858279
TI  - Crystallization of foot-and-mouth disease virus 3C protease: surface mutagenesis
      and a novel crystal-optimization strategy.
AB  - Foot-and-mouth disease virus (FMDV) 3C protease (3C(pro)) plays a vital role in
      virus replication by performing most of the cleavages required to divide the
      viral polyprotein precursor into its functional component proteins. To date, no
      structural information has been available for FMDV 3C(pro), which is an
      attractive target for antiviral drugs. Targeted mutagenesis of surface amino
      acids identified two Cys residues that were detrimental to solubility and
      contributed to the time-dependent formation of a proteinaceous skin in samples of
      purified wild-type protein. Substitution of these amino acids, combined with
      trimming of the N- and C-termini, yielded a 3C(pro) construct that was amenable
      to crystallization. High-resolution diffraction (1.9 A) was only obtained
      following 'iterative screening' in which commercial crystal screening solutions
      were used as additives once initial crystallization conditions had been obtained.

PMID- 15858280
TI  - Leprosy as a challenge to science on the ability to decode its enigma. A
      hypothesis on how to respond.
AB  - In world leprosy nowadays, a favorable epidemiologic trend has been provided due
      to the best effort of the worldwide campaign with chemotherapy providing a bright
      but one-sided look at the future. However, the numbers of new patients are still
      higher than those under chemotherapy, leaving a concern over the remaining non
      human source of infection. To overcome that plausibility, overall understanding
      of the etiology of the disease should be improved. The author discussed this by
      the analyses of historical and scientific legitimacy of the current idea about
      the etiology of leprosy that have unreasonably rejected the possibility of dual
      infections in relation to that of Mycobacterium leprae. The analyses also
      consider the author's ongoing effort to know the feasibility of artificial
      culture of M. leprae by improving of the former methods reported by Skinsnes et
      al. and has been rejected as it contained Mycobacterium scrofulaceum, without
      attention to the coexistent M. leprae at that time. The bacillus thus maintained
      with the modification of the medium still shows PGL-1 immunoreactivity and the
      pathogenicity to cause neuropathy in mice. These strongly suggest the coexistence
      of the above two bacilli throughout past years. The genomic study is in progress
      to prove that hypothesis, the genomes should be alike in nature if proven.

PMID- 15858281
TI  - The relationship between O-antigens and pathogenic genes of diarrhea-associated
      Escherichia coli.
AB  - To evaluate the serogrouping-based diagnosis of diarrheagenic Escherichia coli, a
      total of 1,130 strains of E. coli isolated in several countries were studied. The
      strains were regarded as enterovirulent on the basis of their O-antigens
      determined using a commercially available kit containing 43 antisera, and the
      presence of diarrhea-associated genes (eae, stx, aggR, est, elt, ipaH) was
      evaluated by PCR. Two hundred sixty-three strains of 1,130 (23.3%) were
      identified as diarrheagenic based on the presence of at least one pathogenic
      gene. The probability that E. coli identified as diarrheagenic on the basis of
      serogrouping actually possessed some pathogenic gene was highest for serogroup
      O119 (78.4%); other serogroups with a positive rate for pathogenic genes higher
      than 60% were O111 and O126. No target genes were detected among the strains
      belonging to serogroups O1, O29, O112ac, O143, O158 and O168. Our results suggest
      that, in practice, serogrouping is useful for the identification of diarrheagenic
      E. coli in a very limited number of serogroups.

PMID- 15858282
TI  - Recurrent Klebsiella pneumoniae liver abscess in a diabetic patient followed by
      Streptococcus bovis endocarditis--occult colon tumor plays an important role.
AB  - Klebsiella pneumoniae is the leading cause of liver abscess in diabetic patients
      in Taiwan. We report the case of a diabetic patient with a history of four
      episodes of K. pneumoniae liver abscess within 3 years. The patient later
      developed Streptococcus bovis bacteremia originating from a colon tumor with
      complications of endocarditis, osteomyelitis, and silent splenic abscess. Occult
      colon tumor may have played an important role in our case, with recurrent
      infection arising from colonizers of the gastrointestinal tract. As our case
      shows, the possible association between occult colon tumor and K. pneumoniae
      liver abscess in diabetic patients should be surveyed.

PMID- 15858283
TI  - Population-based estimates of the cumulative risk of hospitalization potentially
      associated with rotavirus diarrhea among children living in two cities in Akita
      Prefecture, Japan.
AB  - A 4-year retrospective population-based survey was conducted in two cities in
      Akita Prefecture, Japan, to estimate the incidence rate and the cumulative risk
      of hospitalization potentially associated with rotavirus diarrhea. At monthly
      occasions of the 3-year-old checkup, we asked each parent if his or her child had
      ever been hospitalized because of rotavirus diarrhea. Based on 3-year follow-up
      of the four consecutive birth cohorts (1996-1999), we calculated the incidence
      rate and the cumulative risk of rotavirus-associated hospitalizations by the age
      of 3 years. The incidence rates of rotavirus-associated hospitalization in 1-year
      old children in Akita city and Honjo city were 9.7 and 16 hospitalizations per
      1,000 children per year, respectively, whereas 1.9% of children in Akita city and
      3.3% of children in Honjo city were hospitalized by their third birthday because
      of rotavirus-associated diarrhea. The burden of rotavirus diarrhea in this region
      of Japan, and probably across the nation, appears substantially large.

PMID- 15858284
TI  - Infection route-independent accumulation of splenic abnormal prion protein.
AB  - The accumulation kinetics of the abnormal form of prion protein (PrP(Sc)) in
      spleens and brains of scrapie (Obihiro-1)-infected mice at various times after
      intracerebral (i.c.), intraperitoneal (i.p.), or oral inoculation were studied.
      PrP(Sc) was first detected by Western blotting with anti-prion protein antibodies
      on days 70 and 116 after i.c. (3 microg) in spleens and brains, respectively.
      Although the amount of cerebral PrP(Sc) gradually increased to the maximum level
      on day 152 after i.c. inoculation, splenic PrP(Sc) established the maximum level
      on day 116 after i.c. inoculation then registered slight decreases up to day 152
      with further incubation. The detectable levels of cerebral PrP(Sc) by Western
      blotting were established on day 231 or 259, whereas those of splenic PrP(Sc)
      were detected on day 94 or 93, after i.p. and oral infection, respectively. The
      splenic PrP(Sc) decreased slightly thereafter. These results indicate that
      splenic PrP(Sc) increased before cerebral PrP(Sc) established a detectable level
      in a manner independent of the inoculation route.

PMID- 15858285
TI  - Reactivity of genotypically distinct hepatitis B virus surface antigens in 10
      commercial diagnostic kits available in Japan.
AB  - Hepatitis B virus (HBV) surface antigen (HBsAg) is one of the most important
      serological markers of current HBV infection. However, there are significant
      antigenic variations of HBsAg caused by genotypic diversity as well as mutation
      of the HBV genome. It is predictable that amino acid substitutions occurring in
      the HBsAg "a" determinant of a particular HBV genotype will affect the
      sensitivity of some diagnostic kits, since all the diagnostic kits currently
      available utilize monoclonal and/or polyclonal antibodies against the "a"
      determinant. One possible concern is that there may be a significant variation in
      the sensitivity of HBsAg diagnostic kits to HBsAg encoded by HBV of different
      genotypes, which might result in a failure to detect HBsAg of a particular HBV
      genotype. In this study, we assessed the reactivity of HBsAg specimens derived
      from three different HBV genotypes (A, B, and C) that are prevalent in Japan by
      10 commercially available EIA (enzyme immunoassay), CLIA (chemiluminescent
      immunoassay), and CLEIA (chemiluminescent enzyme immunoassay) diagnostic kits.
      Specimens included both clinical samples and recombinant HBsAg. Our results
      showed that all the diagnostic kits evaluated were able to detect HBsAg
      irrespective of HBV genotypes. At the same time, it is apparent that some, but
      not all of the kits showed clear differences in sensitivity to the three HBV
      genotypes.

PMID- 15858286
TI  - Immunological detection of severe acute respiratory syndrome coronavirus by
      monoclonal antibodies.
AB  - In order to establish immunological detection methods for severe acute
      respiratory syndrome coronavirus (SARS-CoV), we established monoclonal antibodies
      directed against structural components of the virus. B cell hybridomas were
      generated from mice that were hyper-immunized with inactivated SARS-CoV virion.
      By screening 2,880 generated hybridomas, we established three hybridoma clones
      that secreted antibodies specific for nucleocapsid protein (N) and 27 clones that
      secreted antibodies specific for spike protein (S). Among these, four S-protein
      specific antibodies had in vitro neutralization activity against SARS-CoV
      infection. These monoclonal antibodies enabled the immunological detection of
      SARS-CoV by immunofluorescence staining, Western blot or immunohistology.
      Furthermore, a combination of monoclonal antibodies with different specificities
      allowed the establishment of a highly sensitive antigen-capture sandwich ELISA
      system. These monoclonal antibodies would be a useful tool for rapid and specific
      diagnosis of SARS and also for possible antibody-based treatment of the disease.

PMID- 15858287
TI  - The seroprevalence of parvovirus B19 infection among to-be-married girls,
      pregnant women, and their neonates in Shiraz, Iran.
AB  - Erythema infectiosum (fifth Disease) is the major clinical manifestation of human
      parvovirus B19 (HPV B19) infection. HPV B19 is known to be associated with
      adverse effects on fetuses such as hydrops fetalis, aplastic anemia, intrauterine
      fetal death, and chronic anemia in immunocompromised individuals. The objective
      of this study was to assess seroprevalence to HPV B19 in three different groups
      in Shiraz, Iran. The first group included 91 to-be-married girls. The second
      group included 184 pregnant women and the third group consisted of 184 neonates,
      who were born to the women in the second group. Specific IgG and IgM antibodies
      to HPV B19 were measured using ELISA technique. Results showed that the
      prevalence for IgG to HPV B19 was 56 (61.5%), 127 (69%), and 127 (69%) for the
      first, second, and third groups, respectively. Overall, 183 out of the 275
      (66.5%) women of childbearing age had IgG to HPV B19. The seroprevalence for IgM
      to HPV B19 was 2.2% for the second group. There was no detectable IgM in
      umbilical cord sera or in the first group blood samples. In conclusion,
      approximately one-third of individuals in the study who were of childbearing age
      were at risk for primary HPV B19 infection.

PMID- 15858288
TI  - An outbreak of measles virus infection due to a genotype D9 at a junior high
      school in Yamagata, Japan in 2004.
AB  - We investigated a measles virus (MV) outbreak that occurred at a junior high
      school in Yamagata, Japan between January and February, 2004. We received throat
      swab specimens from three patients at this school and carried out virus isolation
      with Vero/hSLAM cells and virus genome detection by reverse-transcription
      polymerase chain reaction. As a result, we isolated the virus from one patient
      and succeeded in amplifying the MV genome from the others. Further sequence
      analysis of the N gene revealed that these viruses were completely identical, and
      that their genotype could be characterized as type D9, which has not been
      reported in Japan previously. We also identified D9 viruses in two students at
      other junior high schools in Yamagata. These results suggested that D9 strains
      were imported from a region outside Japan. The genotypes of MVs found in Yamagata
      have changed in recent years, with D5 predominating in 2001 and H1 predominating
      in 2002 and 2003 as reported as national surveillance data. Therefore, we should
      monitor carefully to be sure that D9 strains do not become the next predominant
      virus. The more the number of measles cases decrease, the more important become
      the roles of public health laboratories, which genotype MVs and monitor their
      circulation and transmission pathways.

PMID- 15858289
TI  - Antimicrobial resistance of enterococcal blood isolates at a pediatric care
      hospital in India.
AB  - Enterococci are one of the leading causes of nosocomial infections. In recent
      years, enterococci have become increasingly resistant to a wide range of
      antimicrobial agents. From April to October 2001, a study was conducted to
      speciate and determine the antimicrobial susceptibility of 50 isolates of
      enterococci from bacteremic children. These isolates were tested for
      antimicrobial susceptibility to the commonly used antibiotics. Screening for
      vancomycin resistance was done by the agar screen method, and the results were
      confirmed by determining the minimum inhibitory concentration (MIC) using the
      agar dilution method. It was observed that 33 isolates were Enterococcus faecium,
      followed by E. faecalis (10), E. durans (4), and E. dispar (3). Seventy-two
      percent of strains were resistant to ampicillin, 46% to amoxicillin + clavulanic
      acid, 72% to ciprofloxacin, 54% to doxycyclin, and 74% to erythromycin. Sixty-six
      percent of isolates showed high-level gentamicin resistance and 42% showed high
      level streptomycin resistance. Four strains showed raised MIC to vancomycin (8
      microg/ml). It was concluded that multidrug resistant E. faecium is emerging as
      an important agent of bacteremia in children.

PMID- 15858290
TI  - Inducible clindamycin resistance in staphylococci isolated from clinical samples.
AB  - This study aimed to determine the levels of the macrolides-lincosamides
      streptogramins B (MLS(B)) resistance phenotype of Staphylococcus aureus and
      coagulase-negative staphylococci (CNS) isolates from clinical samples. A total of
      521 strains of staphylococci, comprising 230 S. aureus and 291 CNS isolates from
      various clinical samples, were identified by conventional methods. The double
      disc test was applied by placing erythromycin and clindamycin discs on these
      isolates to investigate the inducible and constitutive MLS(B) resistance
      phenotypes and MS phenotype. Among the S. aureus strains, 24.3% showed the
      constitutive and 7.8% the inducible phenotype, while there was no MS phenotype.
      In the CNS strains, 40.2% showed the constitutive and 14.7% the inducible MLS(B)
      resistance phenotype, and 18.2% had the MS phenotype. In both S. aureus and CNS
      strains, the constitutive MLS(B) resistance rate was found to be higher than the
      rate of inducible resistance. By applying double-disc tests on a routine basis to
      detect inducible MLS(B) resistance, clindamycin can be effectively used on
      staphylococcal infections. Additionally, it can be used to survey the MLS(B)
      resistance of staphylococci strains from specific geographical regions or
      hospitals.

PMID- 15858291
TI  - Serum neopterin levels in patients with chronic hepatitis B.
AB  - The aim of this study was to determine the neopterin levels and peripheral blood
      lymphocyte subgroups in HBeAg-positive and -negative chronic hepatitis B
      patients. A total of 89 patients were included in the study. The mean serum
      neopterin level of patients with chronic hepatitis B was significantly higher
      than that of the control group. In HBeAg-positive chronic hepatitis B patients,
      the mean serum neopterin level was significantly higher than that of anti-HBeAb
      positive patients. There was no significant correlation between the serum
      neopterin levels and alanine aminotransferase and HBV-DNA levels in HBeAg
      positive chronic hepatitis B patients. There were no significant differences
      between the control subjects and patients with HBeAg-positive or anti-HBeAb
      positive hepatitis in terms of the percentage of peripheral blood CD4+ or CD8+ or
      the ratio of CD4+/CD8+ lymphocytes. Our results suggest an association between
      elevated neopterin concentrations and HBeAg-positivity in patients with chronic
      hepatitis B. However, there appears to be no association between the neopterin
      levels and either hepatocyte damage or viral replication status.

PMID- 15858292
TI  - Asymptomatic cryptosporiosis in a periurban slum setting in Kolkata, India--a
      pilot study.
AB  - We report the results of a prospective study conducted among asymptomatic
      children of slum dwellers in Kolkata, eastern India, to assess the prevalence of
      Cryptosporidium parvum during the period of October 2002 to July 2003. Of the 609
      fecal samples examined, C. parvum was detected in 14 (2.3%). The study indicated
      that poor sanitary conditions may be cofactors for the cryptosporidial disease
      burden among slum dwellers. The implications of asymptomatic infections have been
      discussed.

PMID- 15858293
TI  - The first reported case of spotted fever in Fukui Prefecture, the northern part
      of central Japan.
AB  - A 53-year-old man visited Mt. Arashima-dake in Fukui Prefecture, and was infested
      by a tick-like organism. He visited a local clinic on July 12, 2004, complaining
      of high fever, general fatigue and rash. After several days without definite
      diagnosis, he was admitted to the Fukui Prefectural Hospital, where he was
      treated with minocycline hydrochloride for 10 days until recovery. His clinical
      symptoms on admission were high fever (39.6 degrees C), erythematous eruption,
      eschar on the right upper arm, and regional lymphoadenopathy. The epidemiological
      status and some clinical findings strongly suggested spotted fever (SF), and SF
      was confirmed based on the finding that his sera were reactive only to antigens
      of the SF group rickettsiae in the indirect immunoperoxidase analysis. This case
      is the first official report of SF rickettsiosis in Fukui Prefecture, the
      northern part of central Japan.

PMID- 15858294
TI  - Detection of rabies-specific antigens by egg yolk antibody (IgY) to the
      recombinant rabies virus proteins produced in Escherichia coli.
AB  - We obtained rabies-specific egg yolk antibodies (IgY) by immunizing hens with
      recombinant His-tagged nucleoprotein and phosphoprotein (rN, rP) of the rabies
      virus (CVS-11 strain) expressed in Escherichia coli. The anti-rN and rP IgY were
      shown to bind specifically to the respective proteins of the CVS-11 strain of
      rabies virus by Western blotting, immune fluorescent assay and
      immunohistochemistry, indicating that IgY to rabies recombinant proteins could
      serve as a reagent for diagnosis of rabies virus infection.

PMID- 15858295
TI  - An outbreak of diarrhea caused by Escherichia coli serogroup O169:HNM harboring a
      coding gene for enteroaggregative E. coli heat-stable enterotoxin 1 (astA) in
      Fukui Prefecture.

PMID- 15858296
TI  - Subtypes of hepatitis B surface antigen in Turkey.

PMID- 15858297
TI  - Active alveolar hydatidosis with sero-negativity for antibody to the 18 kDa
      antigen.

PMID- 15858299
TI  - A study of root canal morphology of human primary molars using computerised
      tomography: an in vitro study.
AB  - Knowledge of the size, morphology and variation of the root canals of primary
      teeth are useful in visualizing the pulp cavity during treatment. This study was
      carried out to investigate the applicability of Computed Tomography in studying
      the root canal morphology of the primary molars. A total of 60 primary
      molars.without any macroscopic root resorption were collected and divided into
      four groups. The samples were arranged in wax block and then scanned for
      evaluation in the CT Scanner both in axial and coronal plane. The results
      obtained from the scanned images were statistically analyzed to know the
      frequency, mean and standard deviation for all the groups. The images showed the
      complexity of the root canals of the primary molars and also several capabilities
      of the CT Scan in advance Endodontic research in primary teeth were observed.

PMID- 15858300
TI  - Mineral trioxide aggregate as a pulpotomy agent in primary molars: an in vivo
      study.
AB  - The retention of pulpally involved deciduous tooth in a healthy state until the
      time of normal exfoliation remains to be one of the challenges for Pedodontists.
      A scientific noise has been generated about several materials some of which have
      been popular pulpotomy medicaments. Concerns have been raised about the toxicity
      and potential carcinogenicity of these materials, and alternatives have been
      proposed to maintain the partial pulp vitality, however to date no material has
      been accepted as an ideal pulpotomy agent. Mineral trioxide aggregate (MTA) is a
      biocompatible material which provides a biological seal. MTA has been proposed as
      a potential medicament for various pulpal procedures like pulp capping with
      reversible pulpitis, apexification, repair of root perforations, etc. Hence the
      present study was done to evaluate the efficacy of MTA as a pulpotomy medicament.
      A clinical and radiographic evaluation was done on children where MTA was used as
      pulpotomy medicament in primary molars for a period of 6 months and it was found
      to be a successful material.

PMID- 15858301
TI  - Oral health status of 5 years and 12 years school going children in Chennai city-
      an epidemiological study.
AB  - India, a developing country, faces many challenges in rendering oral health
      needs. The majority of Indian population resides in rural areas of which more
      than 40% constitute children. The purpose of this study was to assess the oral
      health status of 5 years and 12 years school going children in Chennai city. The
      study population consisted of 1200 school children of both the sexes (600 private
      and 600 corporation school children) in 30 schools, which had been selected
      randomly. The survey is based on WHO, 1999 Oral Health Assessment, which has been
      modified by including gingival assessment, enamel opacities/ hypoplasia for 5
      years. Evaluation of the oral health status of these children revealed, dental
      caries is the most prevalent disease affecting permanent teeth, more than primary
      teeth and more in corporation than in private schools, thereby, correlating with
      the socioeconomic status. It may be concluded that the greatest need of dental
      health education is at an early age including proper instruction of oral hygiene
      practices and school based preventive programs, which would help in improving
      preventive dental behaviour and attitude which is beneficial for life time.

PMID- 15858302
TI  - Dental caries experience and salivary levels of Streptococcus mutans and
      Lactobacilli in 13-15 years old children of Belgaum city, Karnataka.
AB  - The present cross-sectional study was carried out in 372 school going children of
      Belgaum aged 13-15 years. The sample was selected by two stage random sampling
      method. The aim of the study was to estimate the salivary levels of Streptococcus
      mutans and Lactobacilli and to study the relationship between these
      microorganisms and dental caries experience. The DMFT was recorded according to
      the WHO criteria(1997).The microbial load was estimated from a single saliva
      sample obtained from the children. The mean DMFT recorded was 2.41. Streptococcus
      mutans was detected in 87.37% and Lactobacilli in only 36.71% of the sample.
      Statistically, highly significant relation was found between Streptococcus mutans
      and DMFT categories (chi2=125.36, P<0.001), while Lactobacilli was not
      statistically related to DMFT categories (chi2=8.78, P>0.05).

PMID- 15858303
TI  - Class-III malocclusion: genetics or environment? A twins study.
AB  - Etiology of class-III malocclusion is generally believed to be genetic. A wide
      range of environmental factors have been suggested as contributing factors for
      the development of class-III malocclusion. Twin study is one of the most
      effective methods available for investigating genetically determined variables of
      malocclusion. Discordancy for class-III malocclusion is a frequent finding in
      dizygotic twins. However, class-III malocclusion discordancy in monozygotic twins
      is a rare finding. The purpose of this study of monozygotic twins is to assess
      the genetic and environmental components of variation within the cranio-dento
      facial complex.

PMID- 15858304
TI  - Hypohidrotic ectodermal dysplasia: a unique approach to esthetic and prosthetic
      management: a case report.
AB  - Hypohidrotic ectodermal dysplasia is a rare congenital disease that affects
      several ectodermal structures. The condition is usually transmitted as an x
      linked recessive trait, in which gene is carried by the females and manifested in
      males. Manifestations of the disease differ in severity and involve teeth, skin,
      hair, nails and sweat and sebaceous gland. Ectodermal dysplasia is usually a
      difficult condition to manage. Prosthodontically, because of the typical oral
      deficiencies, and afflicted individuals are quite young to receive extensive
      prosthodontic treatment, which restores their appearance and helps them, for the
      development of positive self-image. This case report describes the management of
      upper jaw with over denture with copings on existing teeth i.e. two permanent peg
      shaped centrals as well as lateral incisors. However with adequate of retainer
      lower denture was provided with a new treatment modality.

PMID- 15858305
TI  - Management of temporo-mandibular joint ankylosis in growing children.
AB  - Although temporo-mandibular joint (TMJ) ankylosis is one of the most common
      pathologies afflicting the facial skeleton, it is also the most overlooked and
      under-managed problem in children. The TMJ forms the very cornerstone of cranio
      facial integrity and hence its ankylosis in growing children adversely affects
      the growth and development of the jaws and occlusion. Impairment of speech,
      difficulty in mastication, poor oral hygiene, rampant caries and acute compromise
      of the airway pose a severe psychologic burden on the tender minds of children.
      The aim of this article is to present an overview of efficient management
      strategies, based on a case report, so as to increase its awareness among all
      dental surgeons involved in the treatment of children.

PMID- 15858306
TI  - Cornelia de-Lange syndrome.
AB  - Cornelia De Lange syndrome is a relatively uncommon, multiple congenital anomaly
      / mental retardation disorder of unknown etiology. Its incidence has been
      reported to vary from 1 : 30,000 to 1 : 50,000 of live births, without any known
      racial predilection. However, it has been considered to be due to a new dominant
      mutation. Main clinical features of this syndrome include growth retardation,
      developmental delay, hirsutism, structural limb abnormalities, mental retardation
      and facial growth discrepancies. Main causes of death in such patients include
      pneumonia along with cardiac, respiratory and GI abnormalities.

PMID- 15858307
TI  - Biological aspects of tooth fragment reattachment in immature incisors.
AB  - Tooth fragment reattachment is a relatively new technique and there are many
      aspects which still need to be explored. Reported here is a case of enamel and
      dentin fracture of 11 and 21. There was a very thin layer of dentin clinically
      over the pulp chamber and the root apices were immature. The reattachment
      procedure was modified slightly. The initial joint was made with protective
      calcium hydroxide and glass ionomer cement on the approximating surfaces. The
      further reattachment was accomplished using composites and acid etch technique.
      This was done for pulpal protection. After six months, reattachment was intact
      and successful with no staining, sensitivity or pain. The radiographs revealed
      root completion of the immature incisors. The reattachment procedure proved to be
      biologically superior in addition to its esthetic value and psychological
      advantage.

PMID- 15858308
TI  - Peeping through heart's window: a case report of Fallots tetralogy.
AB  - Tetralogy of Fallot is a congenital heart defect. A combination of four
      abnormalities in heart allow oxygen rich and oxygen-depleted blood to mix. The
      resulting low-oxygen blood then circulates through the body. A child with the
      condition tends to develop slowly, eat poorly and grow slowly and may experience
      "blue" spells on crying and dyspnea on exertion. A 12 year old child with this
      congenital heart defect and cleft palate with cleft lip is discussed. Details of
      the latest diagnostic and treatment procedures are also presented.

PMID- 15858309
TI  - Non-syndrome multiple supplemental supernumerary teeth.
AB  - Multiple supernumerary teeth without any associated systemic conditions or
      syndromes are not common. We document a case of non-syndrome multiple
      supplemental supernumerary teeth in mandibular premolar region of an adolescent
      male patient, an incidental findings during routine radiographic examination.
      Periodic examination is recommended to monitor the clinical behavior.

PMID- 15858310
TI  - Dentigerous cyst associated with permanent central incisor: a rare entity.
AB  - Dentigerous cyst is one of the most prevalent types of odontogenic cyst and is
      associated with crown of an unerupted or developing tooth. Dentigerous cyst is
      more commonly seen with mandibular third molar and maxillary canine and rarely
      other teeth are involved. Here we report a case of dentigerous cyst involving
      permanent maxillary central incisor.

PMID- 15858311
TI  - Sublingual traumatic ulceration due to neonatal teeth (Riga-Fede disease).
AB  - The term Riga-Fede disease has been used historically to describe traumatic
      ulceration that occurs on the ventral surface of tongue in neonates and infants.
      It is most often associated with natal and neonatal teeth in newborns. A case of
      Riga-Fede disease is presented.

PMID- 15858312
TI  - [The meaning and problem of the 8020 movement in Japan].
AB  - In 1982 the Health and Medical Service Law for the elderly was enacted. Until
      1982 medical services for the elderly were provided free or charge in Japan,
      causing rising health expenditure on the elderly. One purpose of the law was to
      introduce partial cost-sharing and health services for the elderly, but dental
      health services were not included in the Law. The 8020 Movement was therefore
      initiated to include dental health within the health service of the Law. The
      "8020" goal is based on research which reported that it is possible to eat almost
      all kinds of food with 20 teeth. In 1989 the Committee for Adult Oral Health of
      the Ministry of Health was established and as an objective for on oral health
      campaign, the 8020 Movement was proposed. Since 1992, activities for the 8020
      Movement by local governments have been supported by the Central Government,
      initiating the success of the 8020 Movement.

PMID- 15858313
TI  - [Epidemiology on the relationship between 8020 and clinical prosthodontics].
AB  - The tooth conditions of Japanese people have improved year by year, and it may be
      possible to achieve 8020 in the near future. On the other hand, over 40% of
      people had experienced prosthodontic treatment including dentures and bridges
      between the age of 45-54, and about 80% between the age of 65-74. Therefore, the
      rate of people who have a prosthodontic crown in their mouth are thought to be
      higher even in the young population. Prosthodontic treatment is important for
      recovering from severe defect of caries or for controlling occlusal trauma
      derived from malocclusion. However, it is difficult to manage prosthetically
      treated teeth for a long time in the oral environment because their treatments
      have been done for those who still have the risk of missing teeth. In this
      report, the relationship between achieving 8020 and prosthodontic treatment is
      discussed with the results of a study on extraction causes and the risks of
      prosthetically treated teeth. The results showed that the main cause of
      extraction of prosthetically teeth was periodontal disease, that 74.1% of the
      prosthetically treated teeth were non-vital, and that the prevalence of root
      fracture was different between vital and non-vital. These findings suggested that
      the comparison of the cause of missing teeth, especially, the risk of missing
      prosthodontically treated teeth, should be discussed after the standardization of
      periodontal conditions.

PMID- 15858314
TI  - [8020 and prosthetic treatments: a review of literature].
AB  - PURPOSE: In order to reveal the relationship between 8020 movement and
      prosthodontic treatments, a systematic review was conducted concerning the
      clinical questions of 1) whether the longevity of abutment teeth is extended by
      prosthodontic treatment, 2) whether prosthodontic treatment can help extend the
      longevity of remaining teeth. METHODS: In order to determine the survival rate of
      the crown and bridge, the prognosis of the abutment of crowns and bridges, the
      influence of removable partial denture and dental implant therapies on the
      survival of remaining teeth, and the survival rates of remaining teeth between
      when the teeth adjacent to missing teeth are treated prosthodontically and when
      not treated, a systematic review using computer online searches was conducted.
      RESULTS: The following results were obtained: 1) Troubles rapidly increase 13
      years after the placement of crowns and bridges. One-third and one-half of crowns
      and bridges can lose their function in 15 and 20 years after placement, 2) Crowns
      and bridges can extend the longevity of their abutment teeth, and 3) Implants and
      bridges can help extend the longevity of the remaining teeth. CONCLUSIONS: The
      clinical impacts of prosthodontic treatments on the 8020 movement cannot be
      neglected, since crowns and bridges and implant therapies can extend the
      longevities of abutment teeth and teeth adjacent to edentulous spaces treated by
      implant.

PMID- 15858315
TI  - [Clinical report on defective dentition].
AB  - The "8020" objective seems difficult to achieve, but at least 20 teeth are needed
      based on difficult cases of defective dentition. Our clinical experience shows
      that at least 18 teeth are needed to keep 4 occlusal supports. If the number of
      occlusal supports falls below 4, defective dentition may easily deteriorate to
      more clinically difficult cases. From our long-term experience, patients over 80
      years old who still have 20 teeth usually have stabilized occlusal supports,
      while many cases who have partially lost their occlusal support do not achieve
      the 8020 goal. Prevention of partial defects of teeth for restoration of caries
      and active prosthesis for defects are important to achieve the 8020 goal.
      Furthermore, continuous follow-up and preventive support are important. If
      continuous clinical correspondence is possible, 8020 may be achievable in about
      80% of all cases.

PMID- 15858316
TI  - [Assessment of beta-tricalcium phosphate as a carrier for bone formation
      promoting agent, TAK-778-SR].
AB  - PURPOSE: The aim of this study was to evaluate the combination of TAK-778-SR
      which was sustained-release microcapsules of a bone formation stimulant, TAK-778,
      and its carrier beta-tricalcium phosphate (beta-TCP) blocks (pore rates 60%, 75%
      respectively). The difference of their abilities in bone-formation was evaluated
      histomorphologically by varying the following conditions: with or without TAK
      778, pore ratio of carrier and embedding period. METHODS: Nine-week-old female SD
      rats were used. After removing the parietal bone from the head with a trephine
      bar, the defects were refilled by beta-TCP blocks immersed with or without TAK
      778 under the following conditions: saline solution, release microcapsules only,
      and release microcapsules with TAK-778 (TAK-778-SR). These rats were sacrificed
      after 5 and 10 weeks and their histological specimens were prepared.
      Morphological change was observed and the formation rates of each new bone were
      compared using an NIH imaging program. RESULTS: A significant amount of new bone
      was morphologically observed in all beta-TCP samples that were treated with TAK
      778-SR. A high rate of new bone formation was confirmed in the 10-week samples
      (pore rate 75%, with TAK-778-SR) with the NIH imaging. CONCLUSIONS: 1. beta-TCP
      and release microcapsules did not disturb the recovery process. 2. Five- and 10
      week samples (pore rate 60%) were absorbed marginally. 3. Absorption was observed
      in the 5-week samples (pore rate 75%), and it was accelerated further at 10
      weeks. 4. An accelerating bone-formation effect of TAK-778-SR was confirmed and
      beta-TCP block was proved to be highly useful as a carriage material.

PMID- 15858317
TI  - [Influence of sleep bruxism on dislodgement of dental restorations].
AB  - PURPOSE: This study investigated the correlation between strength of sleep
      bruxism and dislodgement of dental restorations, by both using the facet index of
      occlusal splint for sleep bruxism and measuring the dislodgement rate of dental
      restorations. METHODS: Subjects consisted of 422 patients with 3673 dental
      restorations (inlay, crown, jointed crowns, and bridge) referred to the hospital
      from 1976 to 2004 who were randomly selected from 912 patients. All patients wore
      an occlusal splint during sleep. Ink was placed on the occlusal part of the
      splint and the strength of sleep bruxism was evaluated by the wearing away of the
      ink and indentation on the splint (Ikeda's method). The subjects were classified
      into the following four groups according to the evaluation: B-0: no facet on the
      splint, B-1: slight facet with wearing of the ink but no indentation on the
      splint, B-2: slight indentation on the splint, and B-3: notable indentation on
      the splint, and then the dislodgement rate between the groups was compared. The
      mean evaluation time in each patient was 10.1 years. RESULTS: The rate of
      patients with dislodgement was B-1: 12.7%, B-2: 35.1%, and B-3: 43.8%. The
      dislodgement rates of categorized restorations in groups B-1, B-2, and B-3 15
      years after the placement were, restorations: 9%, 18%, and 24%, inlay: 19%, 24%,
      and 32%, and crown: 5%, 12%, and 13%, respectively. CONCLUSIONS: It is proved
      that the evaluation method using the facet index of occlusal splint for sleep
      bruxism is a reliable means of estimating how long the restoration will last. The
      results showed that sleep bruxism influences the dislodgement of restorations. To
      protect restorations, it might be effective to control the load from sleep
      bruxism.

PMID- 15858318
TI  - [Kinematic analysis of limitation of mouth opening of temporomandibular disorders
      by rotation and translation of the condyle].
AB  - PURPOSE: The purpose of this study was to determine whether rotation and
      translation of the condyle were useful parameters for identifying causes of
      limitation of mouth opening in patients with temporomandibular disorders (TMD).
      METHODS: In 7 healthy volunteers and 55 patients with TMD, rotation and
      translation of the condyle were measured using a 6 degree-of-freedom jaw movement
      tracking device. Patients were divided into two groups: those who could open
      their mouth 40 mm or greater, and those who could not open their mouth 40 mm. In
      each group, the relationship of rotation and translation of the condyle to
      maximum mouth opening, condition of the articular disc, and pain was determined.
      RESULTS: Both correlations between maximum mouth opening and rotation and
      translation of the condyle were strong, especially the former correlation. There
      was no marked difference in the distribution of range of mouth opening, and
      rotation and translation of the condyle with respect to condition of the
      artticular disc. Muscle pain was associated with reduced mouth opening. Even in
      patients without limited mouth opening, their range of mouth opening was actually
      reduced when they had muscle pain. Among the patients with limited mouth opening,
      joint pain correlated to limited translation of the condyle. However, in patients
      with Wo-Wo condition of articular disc, their translation of the condyle was not
      limited even with joint pain, but it was limited with muscle pain. CONCLUSIONS:
      Rotation of the condyle indicated strong correlation with muscle pain, and so is
      a useful parameter for estimating treatment methods by a surgical approach. On
      the other hand, translation of the condyle showed variations in correspondence
      with combinations of several factors such as opening limitation, condition of the
      articular disc, and pain.

PMID- 15858319
TI  - [Application of sintered Ti powder to dental prostheses].
AB  - PURPOSE: Powder metallurgy is a metal processing technology. Porous titanium
      produced from powder is widely used. The method is applied to titanium, which is
      not easy to cast as it sinters under melting point. In prosthetic dentistry,
      powder metallurgy can be applied to high fusing metal that is biocompatible. In
      this study, we examined the mechanical characteristics of the Ti sheet produced
      by sintering and discussed its application to dental prosthesis manufacturing.
      METHODS: Ti sheets of 1-mm thickness, in which a binder was added to spherical Ti
      powder, were produced with the Doctor Blade Method. The sintering was carried out
      between 900-1150 degrees C at 6 temperatures. The sintered compact was evaluated
      by dimensional change rate, hardness test, bending strength, tensile strength and
      SEM observation. Another compact was sintered on the refractory cast. RESULTS:
      Mechanical strength significantly increased with sintering temperature. In
      addition, excellent mechanical strength was acquired by adding crushed powder and
      performing the de-binder process. In the sintering on the refractory cast, pre
      baking for more than 100 minutes and sintering at over 1050 degrees C was needed
      for practical application. CONCLUSIONS: It thus seems possible to apply sintered
      titanium to dental prostheses. However, it will be necessary to examine the
      control of the shrinkage of the sintered compact in the future too.

PMID- 15858320
TI  - [Effect of prism length on the notchless triangular prism fracture toughness
      test].
AB  - PURPOSE: The purpose of this study was to clarify the effect of holding condition
      with different prism length on the Notchless Triangular Prism (NTP) fracture
      toughness test and to define the prism length as a measuring condition. METHODS:
      Two kinds of NTP prism (ceramic and composite resin) were fabricated by CAD/CAM
      and each prism was adjusted to one of three lengths (8.0 mm, 12.0 mm, 16.0 mm).
      NTP was conducted for prism specimens made under six different conditions. The
      displacement of prism specimen holder gap (Delta d) and maximum fracture load
      (Pmax) were recorded and then a fractogram of each prism was inspected by SEM.
      RESULTS: Inclined stable fracture propagation was observed on the fractogram of
      the 8.0-mm prism. Both Delta d and Pmax of the 8.0-mm prism were significantly
      higher than those of the other lengths. CONCLUSIONS: A prism length of at least
      12.0 mm is needed for the NTP because the 8.0-mm prism did not have a sufficient
      holding condition. The fracture toughness of the ceramic (3.68+/-0.09 MPa.m(1/2))
      was significantly higher than that of the composite resin (2.38+/-0.20
      MPa.m(1/2)).

PMID- 15858321
TI  - [A clinical study on the feeling of oral dryness in denture wearers. Part 1.
      Results of a questionnaire survey].
AB  - PURPOSE: We surveyed youths and denture wearers to evaluate the feeling of oral
      dryness. In the denture wearers group, we evaluated the association between
      dentures and feeling of oral dryness. MATERIALS AND METHODS: The survey was
      performed in 100 denture wearers (mean age, 66.2+/-8.6 years) who visited our
      department from June to October 2003. A similar survey was performed in 50 youths
      (mean age, 25.6+/-2.4 years, 20-29 year-old group). The survey consisted of a
      questionnaire and oral and denture examination. The questionnaire asked about
      oral dryness symptoms, general condition and current medications. The oral and
      denture examination examined the condition of the remaining teeth, the kinds of
      prosthesis, materials of dentures and form of the denture base. RESULTS: A
      feeling of oral dryness was observed in 11 of the 20-29 year-old group (22%) and
      48 denture wearers (48%), hence the incidence was significantly higher in the
      denture wearers group (p<0.01). No association was observed between the oral
      dryness symptoms and age, sex, general condition, current medications, or number
      of residual teeth. The kinds of prosthesis (no denture, partial denture, complete
      denture) and form of the denture base have no relationship with the feeling of
      oral dryness. CONCLUSIONS: 48% of the denture wearers had the feeling of oral
      dryness, and the incidence was higher than in the 20-29 year-old group. However,
      no association was observed between the oral dryness symptoms and dentures.
      Further studies are necessary to evaluate factors associated with the development
      of the feeling of oral dryness.

PMID- 15858322
TI  - [A clinical study on the feeling of oral dryness in denture wearers. Part 2.
      Measurement of the height of the salivary moisture area].
AB  - PURPOSE: We surveyed youths and denture wearers to evaluate the feeling of oral
      dryness. MATERIALS AND METHODS: The survey was performed in 100 denture wearers
      (mean age, 66.2+/-8.6 years) who visited our department from June to October
      2003. A similar survey was performed in 50 20-29 year-old persons (mean age,
      25.6+/-2.4 years). Measurement of the height of the salivary moisture area, and
      detection of Candida were performed. We used Saliva Wet Tester for measuring the
      height of the salivary moisture area. RESULTS: The mean height of the salivary
      moisture area was significantly lower in the denture wearers group than in the 20
      29 year-old group (p<0.05). No association was observed between the height of the
      salivary moisture area and general condition, current medications, number of
      residual teeth, or the denture base. In the denture wearers group, the height of
      the salivary moisture area was high in patients with bounded saddle dentures or
      unilateral distal extension dentures in either or both jaws but low in those with
      dentures covering the entire palatal and lingual mucosa in both the upper and
      lower jaws. However, the feeling of oral dryness was not always consistent with
      the height of the salivary moisture area. In the denture wearers group, the
      height of the salivary moisture area matched the low tendency of detection of
      Candida of 100 CFU or more in patients. CONCLUSIONS: The mean height of the
      salivary moisture area was significantly lower in the denture wearers group than
      in the 20-29 year-old group. However, the feeling of oral dryness was not always
      consistent with the height of the salivary moisture area. Further study,
      including a mental factor, is necessary.

PMID- 15858323
TI  - [The usefulness of an oral moisture checking device (Moisture Checker for
      Mucus)].
AB  - PURPOSE: An oral moisture checking device is easy to use for the examination of
      oral dryness during clinical procedures. This study examined the usefulness of an
      oral moisture checking device. METHODS: The subjects in the examination of
      factors that influence the measured value of the oral moisture checking device
      were 16 sound adults (mean age 27.5). The subjects in the examination of
      measuring the moisture of sound adults were 32 adults (mean age 24.4). In the
      factors that influence the measured value of the device, the measuring pressure
      was examined by comparing the measured value with a trial stopper and without the
      stopper. The factor of sensor cover was examined by comparing the measured value
      before and after changing the sensor cover. The factor of device was examined by
      comparing the measured value using the two devices. The moisture of sound adults
      was measured at the lingual mucosa and buccal mucosa. RESULTS: The measured value
      with a trial stopper was lower by 0.2-0.3% than that without the stopper. The
      measured value differed before and after changing the sensor cover by 0.5-0.8%.
      The measured value was not different among devices. The mean value of the
      moisture of sound adults was 30.6+/-0.3% at the lingual mucosa, and 30.9+/-0.3%
      at the buccal mucosa. CONCLUSIONS: The measurement errors of the oral moisture
      checking device were within 1% under the condition of proper measuring pressure.
      Additionally, the moisture of sound adults converged toward definite values. The
      results of this study suggested that the oral moisture checking device is useful
      for the examination of xerostomia.

PMID- 15858324
TI  - [A case report of removable partial denture with I-C attachment].
AB  - PATIENT: The alveolar bone and teeth for a patient involved in a traffic accident
      were prepared using removable partial dentures with I-C attachment. DISCUSSION:
      Because of using no clasp in the front teeth, sufficient supporting force of the
      dentures and no throbbing pain after insertion of the dentures, the patient was
      fully satisfied with the appearance and functional results of the treatment.
      CONCLUSION: In a case of loss of front teeth, the patient was content with the
      smaller and esthetically excellent attachment instead of a clasp. Moreover, the
      patient is progressing favorably. It is considered that the I-C attachment was
      effective for this case.

PMID- 15858325
TI  - [Reconstruction of bilateral occlusal-supporting area with removable partial
      dentures: a case report].
AB  - PATIENT: The patient (57-years-old female) suffered from severe chronic
      periodontitis in the maxillary and mandibular molar regions. After extraction of
      these teeth, treatment dentures were immediately placed in the maxilla and
      mandible to restore the occlusal-supporting area. Final denture treatment was
      done by adjusting the provisional dentures according to the patient's concern.
      Good prognosis was obtained during 9 years. DISCUSSION: To restore bilateral
      occlusal-supporting areas, treatment dentures reduced the loss of remaining
      teeth. CONCLUSION: Treatment dentures can stabilize the occlusal relationship
      immediately after loss of occlusal-supporting area, and may also contribute the
      patient's acceptance of and satisfaction with the final prostheses.

PMID- 15858326
TI  - [A case report of prosthodontic treatment for the influence of occlusal discord
      on the whole body].
AB  - PATIENT: The patient was a 19-year-old man who visited the hospital with chief
      complaints of headache, stiffness of shoulders, and giddiness. The skull,
      mandible, and splint, and their relation with cervical vertebra, were considered,
      and new knowledge was acquired. Since the fulcrum of the movement axis at the
      time of opening and closing had shifted below the dens, it was diagnosed as TMD.
      Splint treatment was performed and the main symptoms had improved 3 months later.
      DISCUSSION: It is thought that the jawbone of the upper and lower sides of class
      II occlusion had adapted to class III, and would cause various whole-body
      conditions. CONCLUSION: Although the influence of the posture of cervical
      vertebra and the whole-body deformation of submaxilla is considered, there are
      many unknown points and further study is required.

PMID- 15858327
TI  - [A case of unilaterally designed obturator prosthesis].
AB  - PATIENT: A 50-year-old female patient with minor maxillary defect was afflicted
      with an ipsilateral oroantral fistula. A unilaterally designed obturator was
      constructed for the patient. She was satisfied with the obturator because no
      leakage or seepage into the antrum occurred during mastication. It was also
      aesthetically acceptable due in particular to the small size of the denture. In
      this clinical report, treatment with the unilaterally designed obturator is
      discussed. DISCUSSION: The use of functional impression techniques during the
      trial denture stage registered the optimal shape of the soft tissues while they
      were loaded under a variety of functional conditions. This acted to distribute
      the functional forces to the saddle area proportionally and prevented any leakage
      and seepage of food into the defect. CONCLUSION: The unilaterally designed
      obturator prosthesis has served to restore masticatory function as well as to
      obturate the maxillary defect.

PMID- 15858328
TI  - [A case of interdental papillae growth by application of maxillary anterior
      crowns].
AB  - PATIENT: The patient had esthetically unacceptable maxillary anterior crowns.
      Provisional restorations in consideration of the smile line were used for the
      maturation of periodontal tissues. Owing to full regeneration of interdental
      papillae, small black triangles that existed in the gingival embrasure
      disappeared six months after the luting of final restorations. DISCUSSION: We
      should not overlook the importance of physiological occlusion for the management
      of healthy periodontal tissues. CONCLUSION: To create a natural-looking esthetic
      prosthesis, the dentist should strive to create an ideal environment for the
      technician to fabricate functional and esthetic restorations.

PMID- 15858329
TI  - [A case report of median diastema with deep bite treated with resin bonded
      retainer after minor tooth movement].
AB  - PATIENT: A fifty-two-year old female patient visited our dental hospital due to
      periodontal disease and aesthetic complaint by median diastema. A resin bonded
      retainer for the upper anterior teeth was placed after periodontal treatment and
      minor tooth movement. Median diastema and periodontal disease have not relapsed
      for these 6 years. DISCUSSION: Prosthetic treatment combined with minor tooth
      movement enabled the recovery of healthy periodontal tissue and reduction of the
      amount of tooth structure to be prepared. As a result, pulp treatment was not
      involved and desirable tooth contour was successfully achieved. CONCLUSION:
      Prosthetic restoration by resin bonded retainer followed by periodontal treatment
      and minor tooth movement was useful to improve aesthetic problems and to recover
      and maintain healthy periodontal tissue in this case of a patient with
      periodontal disease and median diastema with deep bite.

PMID- 15858330
TI  - [A case of dental implant treatment with sinus lift for the maxillary molar
      sites].
AB  - PATIENT: Implant treatment with sinus lift was conducted in a 53-year-old male
      patient who had bilateral edentulous posterior maxilla with a limited bone volume
      of the sinus floor. One year later, the mobility at the anterior teeth of the
      maxilla increased and then decreased due to occlusal adjustment. The left
      posterior teeth of the mandible were extracted due to severe periodontitis and
      two implants were placed. DISCUSSION: In this case, the patient was highly
      satisfied with the above treatment. When the eccentric movement is guided by
      natural teeth in implant oral rehabilitation, it is important for the long-term
      results to consider the change of the occlusal contact. CONCLUSION: Implant
      treatment with bone augmentation is useful to obtain excellent clinical results
      in spite of the commensurate difficulties for the patient.

PMID- 15858331
TI  - [Implant-supported restoration in the free-end partially edentulous mandible: a
      clinical report].
AB  - PATIENT: A 60-year-old woman presented to the Clinic at Health Science University
      of Hokkaido on September, 1997. The patient's chief complaint was difficulty in
      chewing due to pain with tooth clenching of a fixed partial denture in the left
      mandible. This clinical report describes a treatment approach using implant
      supported fixed prostheses by two dental implants after extraction of the
      abutment teeth. DISCUSSION: She tried to use the fabricated mandibular removable
      partial denture but disliked the lingual bar. After discussing a treatment plan
      using implant-supported fixed prostheses, a decision was made to place implants
      in the free-end partially edentulous mandible. CONCLUSION: The patient was
      followed for 4 years with no surgical or prosthetic complications. It is
      suggested that a dental implant for prosthetic treatment may improve the quality
      of life of the patient.

PMID- 15858332
TI  - [A case report of implantation in augmented bone by guided bone regeneration
      technique].
AB  - PATIENT: A 53-year-old female with root fracture of the second premolar in the
      right mandible underwent implant therapy. After extraction, the GBR (guided bone
      regeneration) technique was applied to the bone defect in June 2000. At 6 months
      after GBR, implants were placed in the augmented bone. The final prosthesis was
      restored in July 2001. DISCUSSION: The bone around the implants was evaluated by
      using X-ray CT images, before and after GBR, and three years after final
      restoration. The three images showed the same bone conditions around the
      implants. CONCLUSION: It is important to evaluate bone condition around implants
      using X-ray CT. Bone defects can be augmented by the GBR technique, and the bone
      condition around the implants was stable after function.

PMID- 15858333
TI  - [Improvement of chewing ability by complete denture: a case report].
AB  - PATIENT: A 58 year-old female patient visited the clinic with chief complaint of
      chewing difficulty with her complete dentures. These dentures did not have a
      sufficient size of denture base and the resin teeth were completely ground down.
      Treatment dentures were inserted and the form was transferred to final dentures.
      DISCUSSION: The risk of re-treatment and adjustment after the denture insertion
      was reduced by using the treatment dentures. The Cochrane Library reported that
      there is no difference between complete dentures and implant supported over
      dentures in terms of patient satisfaction/chewing ability, provided the patient
      has an adequate mandibular ridge. CONCLUSION: Treatment dentures are important to
      reduce the risk of re-treatment.

PMID- 15858334
TI  - The development of the International Space Station centrifuge.
AB  - Gravitational biology research facility "Centrifuge" is currently under
      development for the International Space Station. Research in the Complex Organism
      Biology, indispensable to the progress in Health Science, is only possible in the
      Centrifuge aboard the station. So, on-orbit 1 G controls for various specimens
      including small mammals, fish, and higher plants will be rigorously done in the
      Centrifuge. This facility is also capable of providing "reduced gravity" likely
      on the Moon or on Mars. Thus, it will play a key role in creating knowledge of
      space fundamental biology. As part of the offset of NASA's Shuttle launch
      services for the Japanese Experiment Module, JAXA is developing the Centrifuge
      Rotor (CR), the Life Sciences Glovebox (LSG) and the Centrifuge Accommodation
      Module (CAM). Critical Design Review (CDR) of LSG was conducted on July 2004,
      while the system CDRs of the CAM and CR are scheduled for December 2004 and
      August 2005, respectively. Their launch schedules are under review.

PMID- 15858335
TI  - Fate of allelopathic substances in space--allelopathy of velvet bean plant and
      gravity.
AB  - Interactions between organisms and species have been long known. It has not been
      known that the interactive phenomena (allelopathy) may (or may not) differ in
      space from those on earth. We have studied the gravitational effects on
      allelopathy by exposing a plant-plant system to pseudo-microgravity, which was
      generated by a 3D-clinostat. We hypothesized that allelopathy would be modified
      under altered gravity. L-DOPA (L-3,4-dihydroxyphenylalanine) is known to be the
      major substance in the allelopathy of velvet bean, released from its root. It has
      been found that there have been some differences of the allelopathic action of
      velvet bean plant under pseudo-microgravity. Biosynthesis, release, transport and
      sensing mechanism associated with allelopathy might be affected by gravity.

PMID- 15858336
TI  - Perception mechanism of gravistimuli in gravity resistance responses of plants.
AB  - Gravity resistance is a response that enables plants to develop against the
      gravitational force. Hypergravity conditions produced by centrifugation have been
      used to analyze the mechanisms of gravity resistance responses. Under
      hypergravity conditions, plants construct short and thick shoots and increase
      cell wall rigidity for resisting the gravitational force. Hypergravity caused a
      decrease in the percentage of cells with transverse microtubules, and an increase
      in that with longitudinal microtubules. Such a prompt reorientation of cortical
      microtubules is involved in the changes in morphology of shoots by gravity.
      Hypergravity increased cell wall rigidity by increasing the molecular mass of
      xyloglucans via suppression of xyloglucan breakdown as well as by the thickening
      of cell walls. Blocker reagents of mechanoreceptors nullified the above-mentioned
      changes induced by hypergravity. Gravity resistance responses were brought about
      normally in mutants deprived of gravitropism. This result indicates that the
      graviperception mechanism in gravity resistance is independent of that in
      gravitropism. Gravity resistance responses were brought about independently of
      the direction of gravistimuli, but the responses disappeared in the presence of
      blockers of mechanoreceptors. Thus, in gravity responses, plants may perceive the
      gravitational force independently of the direction of stimuli by mechanoreceptors
      on the plasma membrane, and may utilize the signal to construct a tough body.

PMID- 15858337
TI  - Automorphosis and auxin polar transport of etiolated pea seedlings under
      microgravity conditions.
AB  - On STS-95 space experiment, etiolated pea (Pisum sativum L. cv. Alaska) seedlings
      showed automorphosis and activities of auxin polar transport in epicotyls were
      substantially suppressed. These results together with the fact that inhibitors of
      auxin polar transport induced automorphosis-like growth and development strongly
      suggested that there are close relationships between automorphosis and auxin
      polar transport in etiolated pea seedlings. In order to know how gravistimuli
      control auxin polar transport at molecular levels, we isolated novel cDNAs of
      PsPIN2 and PsAUX1 encoding putative auxin efflux and influx carriers from
      etiolated pea seedlings. Significantly high levels in homology were found on
      nucleotide and deduced amino acid sequences among PsPIN2, PsPIN1 (accession no.
      AY222857) and AtPINs, and between PsAUX1 and AtAUX1. Exogenously applied auxin
      substantially enhanced the expression of PsAUX1 and PsPIN2 as well as PsPIN1.
      Simulated microgravity conditions on a 3-dimensional clinostat remarkably
      increased gene expression of PsPIN1 and PsAUX1 in the hook and the 1st internode
      of pea epicotyls, while the increase of expression of PsPIN2 in both organs was
      not so much. These results suggest that PsPINs and PsAUX1 are auxin-inducible
      genes, and the expression of PsPINs and PsAUX1 is under the control of
      gravistimulation. A possible role of these genes in regulating auxin transport
      relevant to automorphosis of etiolated pea seedlings is also discussed.

PMID- 15858338
TI  - Up and down asymmetrical world for flower blooming.
AB  - Form of plant body shows vertical polarity. Photosynthetic organs deploy upwards
      to seek light. Root system extends downward for water. In addition to this major
      polarity, flowers has similar features, because they bloom in the world where up
      and down asymmetry dominates. Many flowering plants co-evolved with pollinator
      animals. Success of their reproduction is linked to the shape of flower organs in
      many ways. Orientation of inflorescence and each individual flowers, arrangement
      and shape of flower organs exhibit various up and down asymmetry. Some flowers
      mimic female of its pollinator animal. In such case, posture of the target animal
      is copied to the flower. Since animal posture and shape have vertical polarity,
      flower happens to equip same kind of polarity. Tropic response of pistils is
      another up and down feature that improves fitness of flowering plants. Certain
      lily flowers show phototropism to bend pistil upward. Azalea flower depends on
      gravity as the major environmental cue, and light as the secondary signal for up.
      Molecular machinery for those tropic responses seems to be shared with other
      tropism expressed in shoot and root. However, certain differences are found in
      distribution of sediment amyloplast, or spatial allocation of photo-sensing and
      bending site. Tropic responses result in adaptation of those flowers against
      behavior of pollinator animals and terrestrial environment, where gravity affects
      living organisms and interaction among them.

PMID- 15858339
TI  - Graviregulation mechanism of woody stem growth on earth.
AB  - We have been studied the weeping habit of Japanese flowering cherry tree in the
      field of Tama Forest Science Garden, Forestry and Forest Products Research
      Institute at the foot of Mt. Takao. Since cherry trees at various age were the
      materials for our plant physiology experiments, our studies were conducted in the
      fields where we experienced certain difficulties. Even under such difficult
      environment that was rather unexpected and uncontrollable, we could obtain
      fruitful results on the growth of cherry tree, and found them scientifically
      significant, especially in terms of biological effects of gravity on earth.
      Moreover an interesting interaction of cherry tree with various kinds of birds
      was also observed.

PMID- 15858340
TI  - Discussion for animal experiments in space: ethical standard and responsibility
      of researchers for space experiments using laboratory animals.
AB  - International efforts to standardize regulations and study designs and to promote
      the principles of Reduction, Replacement, and Refinement (the 3 Rs) have reduced
      and refined animal use. In NASA ARC and KSC, researchers are responsible only for
      activities related directly to the conduct of their animal experiments. The IACUC
      plays an important role in conformity with NIH policies. Even if researchers
      design protocols of the space life science in Japan, the animal experiments
      should be carried out under the global harmonized conditions in accordance with
      NIH/NASA policies, guides and rules. It is important that researchers himself
      must look forward the ethical animal experiment.

PMID- 15858341
TI  - Animal experiments using mammals are essential to the study on the mechanisms of
      phenomena produced in the human body in the space environment.
AB  - The animal experiments have contributed to the physiology and medicine concerned
      with the care and cure of patients as well as with an understanding of mechanisms
      of various diseases and human health. In particular, the numerous mammals have
      been used for the medical researches. Similarly, to investigate the phenomena in
      the human body that occur in the space environment, the various mammals have been
      used for the medical researches in space. Since the human with frontier spirits
      will never stop continuing the space development and utilization, the space
      medical and physiological researches using mammals as well as subjects are more
      important and necessary for the future space activities. The mammal modules in
      spacecrafts and space station are produced for the rodents at this time.
      Therefore, from various viewpoints, the rats and mice are the first choice for
      space mammal experiments of medical or life science researches and space modules
      for the mammal should be carefully and extensively designed.

PMID- 15858342
TI  - The mechanisms underlying neuromuscular changes in microgravity environment.
AB  - We reported that the levels of electromyogram in soleus muscle and the afferent
      neurogram recorded at L5 segmental level of the spinal cord were instantly
      decreased in response to exposure to microgravity (micro-G) environment created
      during a parabolic flight, although these activities were constantly presented at
      1-G. It was also observed that the soleus muscle length was passively shortened
      in micro-G due to the plantarflexion of ankle joint. Similar phenomena were also
      induced by acute hindlimb suspension at 1-G. Further, the soleus muscle
      atrophied, if the dorsal root at L5 was transected. These results suggested that
      the unloading-related effects on muscle are closely associated with the
      inhibition of the afferent input. However, effects of gravity on most of the
      cells in the whole body can not be removed, although hindlimb suspension can
      inhibit the antigravity activity of rat hindlimb muscles. And parabolic flight
      can create micro-G only for a short period of time. Further, effects of
      hypergravity before and after micro-G are unavoidable. Therefore, further
      experiments utilizing space environment are essential.

PMID- 15858343
TI  - Animal habitats for space experiments.
AB  - There has been little opportunity for flight experiments using small animals, due
      to delay of construction of the International Space Station. Therefore, proposals
      using small animals have been unfortunately excepted from International Space
      Life Sciences Experiment application opportunity since 2001. Moreover, NASA has
      changed their development plan of animal habitats for space experiments according
      to changes of the U.S. space policy and the outlook is not so bright. However,
      international researchers have been strongly requesting the opportunity for space
      experiments using small animals. It will be also important for Japanese
      researchers to make a request for the opportunity. At the same time, researchers
      have to make an advance in ground based studies toward space experiments and to
      respond future application opportunities immediately. In this symposium, we
      explain the AEM (Animal Enclosure Module), the RAHF (Research Animal Holding
      Facility), and the AAH (Advanced Animal Habitat). It will be helpful for
      investigators to have wide knowledge of what space experiment is technically
      possible. In addition, the sample share program will be introduced into our
      communities. The program will provide many researchers with the organs and
      tissues from space-flown animals. We will explain the technical aspect of sample
      share program.

PMID- 15858344
TI  - Contribution of radiation-induced, nitric oxide-mediated bystander effect to
      radiation-induced adaptive response.
AB  - There has been a recent upsurge of interest in radiation-induced adaptive
      response and bystander effect, which are specific modes in stress response to low
      dose/low-dose rate radiation. Recently, we found that the accumulation of iNOS in
      wtp53 celIs was induced by chronic irradiation with gamma rays followed by acute
      irradiation with X-rays, but not by each one, resulting in an increase in nitrite
      concentrations of medium. It is suggested that the accumulation of iNOS may be
      due to the depression of acute irradiation-induced p53 functions by pre-chronic
      irradiation. In addition, we found that the radiosensitivity of wtp53 cells
      against acute irradiation with X-rays was reduced after chronic irradiation with
      gamma rays. This reduction of radiosensitivity of wtp53 cells was nearly
      completely suppressed by the addition of NO scavenger, carboxy-PTIO to the
      medium. This reduction of radiosensitivity of wtp53 cells is just radiation
      induced adaptive response, suggesting that NO-mediated bystander effect may
      considerably contribute to adaptive response induced by radiation.

PMID- 15858345
TI  - Effects of irradiated medium on chromatid aberrations in mammalian cells using
      double mylar dishes.
AB  - We examined the potential contribution of irradiated medium on the bystander
      effect using custom made double-mylar stainless steel rings. Exponentially
      growing Human-hamster hybrid (AL) cells were plated on either one or both sides
      of double-mylar dishes 2-4 days before irradiation. One side (with or without
      cells) was irradiated with alpha particles using the track segment mode of a 4
      MeV Van de Graaff accelerator at the Radiological Research Accelerator Facilities
      of Columbia University. Since alpha particles can only traverse a very limited
      distance, cells plated on the other side of a medium-filled mylar dish will not
      be irradiated by the alpha particles. The results of chromosomal aberrations on
      un-irradiated target cells that were attached to the top mylar layer indicate
      that the number of chromatid-type aberrations was higher when there was a bottom
      layer of cells in the medium filled chambers than just medium alone. Furthermore,
      when transferring the medium from these cell-irradiated dishes to fresh AL
      cultures, chromatid-type aberrations were produced in the un-irradiated fresh
      cells. In contrast, medium irradiated in the absence of cells had no effect on
      chromatid aberrations. These results suggest that certain modulating factors
      secreted from the irradiated cells on the bottom mylar layer into the medium,
      induce chromatin damage in the un-irradiated, bystander cells.

PMID- 15858346
TI  - Detection of adaptive response at chromosome level.
AB  - We have just started the basic study to detect the genetic alterations at
      chromosome level as a result of radioadaptive response. The assay system is based
      upon the analysis of loss of heterozygosity (LOH) induced in human lymphoblastoid
      cell TK6, which were pre-irradiated with low-doses of ionizing radiation (IR)
      before the challenging irradiation. In our previous study, this analysis was
      shown to be very sensitive to IR because the radiation-specific hemizygous LOHs
      (interstitial deletions) were observed after 10 cGy of IR (X-rays or accelerated
      carbon-ion beam). Here, we would like to introduce our plan how to detect the
      changes in such radiation-specific LOH patterns by the pre-irradiation of TK6. If
      we succeed the detection, the radioadaptation assay system can be used for
      elucidating the biological effects of low-doses of space ionizing radiation. In
      addition, we are also considering the modification of assay system by introducing
      the site-specific chromosome breakage (DNA double-strand break) instead of
      challenging IR. Furthermore, the preliminary results of the experiments using
      frozen TK6 cells for the preparation of ISS experiments.

PMID- 15858347
TI  - Effects of heavy ion to the primary [correction of rimary] culture of mouse brain
      cells.
AB  - To investigate effects of low dose heavy particle radiation to CNS system, we
      adopted mouse neonatal brain cells in culture being exposed to heavy ions by
      HIMAC at NIRS and NSRL at BNL. The applied dose varied from 0.05 Gy up to 2.0 Gy.
      The subsequent biological effects were evaluated by an induction of apoptosis and
      neuron survival focusing on the dependencies of the animal strains, SCID, B6,
      B6C3F1, C3H, used for brain cell culture, SCID was the most sensitive and C3H the
      least sensitive to particle radiation as evaluated by 10% apoptotic criterion.
      The LET dependency was compared with using SCID and B6 cells exposing to
      different ions (H, C, Ne, Si, Ar, and Fe). Although no detectable LET dependency
      was observed in the high LET (55-200 keV/micrometers) and low dose (<0.5 Gy)
      regions. The survivability profiles of the neurons were different in the mouse
      strains and ions. In this report, a result of memory and learning function to
      adult mice after whole-body and brain local irradiation at carbon ion and iron
      ion.

PMID- 15858348
TI  - Microtubule dynamics and the regulation by microtubule-associated proteins
      (MAPs).
AB  - Individual microtubules (MTs) repeat alternating phases of polymerization and
      depolymerization, a process known as "dynamic instability." The dynamic
      instability is regulated by various protein factors according to the requirement
      of cellular conditions. Heat-stable MAPs regulate the dynamic instability by
      increasing the rescue frequency. To explore the influence of MAP2, a heat-stable
      MAPs abundant in neuron, on in vitro MT dynamics, the distribution of MAP2 on
      individual MTs was correlated with the dynamic phase changes of the same MTs by
      optical microscopy. MAP2 distributed inhomogeneously along the length of MTs by
      forming high-density regions, clusters. Stops of depolymerization were always
      found to occur only at the cluster sites. Every cluster did not stop
      depolymerization, but depolymerization did always stop at a cluster site. We
      suggest that mode of distribution along MT is an important factor of the function
      of heat-stable MAPs.

PMID- 15858349
TI  - Roles of collagen fibers and its specific molecular chaperone: analysis using
      HSP47-knockout mice.
AB  - Collagen is the most abundant protein of mammals and produces highly organized
      ultrastructures in the extracellular matrix. There are at least 27 types of
      collagen in mammalian tissues. While fibrillar collagen (eg. types I, II, III, V
      and XI) assembles into large fibril structures in the extracellular matrix, type
      IV collagen produces meshwork-like structures in the basement membranes. As
      collagen has a distinct triple helix structure composed of Gly-X-Y repeats whose
      Y position is often hydroxyproline, its folding and maturation process differs
      considerably from globular proteins. Type I collagen is an assembly of two alpha
      1 chains and one alpha-2 chain, and each of the alpha chains contain the N
      terminal propeptide, C-terminal propeptide and central triple helical region. The
      47-kDa heat shock protein (HSP47) is an endoplasmic reticulum (ER)-resident
      molecular chaperone that specifically recognizes the triple helical region of
      collagen and is required for productive folding and maturation of collagen
      molecules. Only in the presence of HSP47, collagen type I molecules can be
      assembled into the correctly folded triple helices in the ER of mouse embryos
      without producing misfolded or non-functionally aggregated molecules. HSP47
      knockout embryos die just after 10.5 day due to the absence of functional
      collagen. Recent our data demonstrated that the non-fibrillar network-forming
      collagen type IV also requires HSP47 for productive folding and maturation. Here,
      we discuss the role of HSP47 in the folding and maturation of collagen type IV as
      well as type I.

PMID- 15858350
TI  - Extracellular matrices as elastic scaffold and mechanical interaction.
AB  - Development of spatial pattern and form is one of the central issues in
      embryology and is included under the general name of morphogenesis. Recently,
      many investigations have revealed how does development occurs by each embryonic
      stem cell or which Genes play a crucial role for morphogenesis. However, still
      fundamental question is unclear; such as how does each cell recognize spatial
      information or which kind of information guides each cell to the suitable place.
      Approximately, we have 6x10(13) cells in our body. If each frame of reference of
      each cell is included in the gene, gene must have included more than 6x10(13) of
      information to inform each cell where they are. We could simply suggest this kind
      of the idea is quite wrong because we know genes are few enough to include such
      informations. Recently, it has been suggested that interaction between
      intracellular and extracellular fiber play crucial roll for morphogenesis. The
      fibers inside cell are quite complicated but well organized the system, and
      fibers outside of the cell are comparatively very simple fiber. Each of the
      fibers is well studied, but quantitative investigation of their interaction is
      lacking although importance is suggested by many researchers. A major problem is
      lacking of new method or technique. In our topics, we would like to introduce how
      intracellular and extracellular fiber generate morphogenesis and how we could
      investigate them using new technique for tissue engineering, one of the promising
      field of applied cell biology.

PMID- 15858351
TI  - The effects of simulated microgravity on avian embryonic development.
AB  - Based on the few reports available, microgravity (MG) can have adverse effects on
      the early development of vascularised extra-embryonic membranes in avian eggs.
      Whether gravity or oxygen availability is the stimulus for development of the
      blood vessels in the chorioallantoic membranes (CAM) remains unclear. Under
      gravity the blastoderm forms on top of the yolk sac, closest to the oxygen rich
      region beneath the shell membranes, and from there the CAM buds from an abdominal
      extension subsequently to form a close contact with shell membranes. Then as the
      embryo develops it spreads beneath the eggshell surface to maximise the surface
      area of the CAM vascular bed available for O2 uptake. To investigate how
      simulated MG influences development of the CAM and embryo we conducted
      experiments on chicken embryos during incubation in a 3D-clinostat (control or
      continuous MG treatment at 5 rpm). Further, to determine if CAM angiogenesis is
      directed towards regions of high O2 tension or gravity we investigated the
      effects of wax treatment (50% shell surface area) on development in MG. We found
      that clinostat MG caused embryonic failure between day 0-5 by preventing normal
      development of CAM-shell membrane complex. Thereafter acute MG promoted increases
      in CAM mass, but did not affect embryo mass. Preliminary findings suggest that
      combined acute MG and wax treatment did not significantly affect embryonic growth
      in either MG or control groups, but retarded CAM growth in control embryos only.
      Finally, we will present evidence to show that acute and prolonged exposure to MG
      does not prevent normal growth and hatching, but might have more subtle effects
      on hatchling physiology, including reduced heart mass.

PMID- 15858352
TI  - Role of gravity in mammalian development: effects of hypergravity and/or
      microgravity on the development of skeletal muscles.
AB  - Effects of hindlimb suspension or exposure to 2-G between postnatal day 4 and
      month 3 and of 3-month recovery at 1-G environment on the characteristics of rat
      hindlimb muscles were studied. Pronounced growth inhibition was induced by
      unloading, but not by 2-G loading. It is suggested that the development and/or
      differentiation of soleus muscle fibers are closely associated with gravitational
      loading. The data indicated that gravitational unloading during postnatal
      development inhibits the myonuclear accretion in accordance with subnormal
      numbers of both mitotic active and quiescent satellite cells. Even though the
      fiber formation and longitudinal fiber growth were not influenced, cross
      sectional growth of muscle fibers was also inhibited in association with lesser
      myonuclear domain and DNA content per unit volume of myonucleus. Unloading
      related inhibition was generally normalized following the recovery.

PMID- 15858353
TI  - Effects of microgravity on organ development of the neonatal rat.
AB  - We analyzed various organs in the same rats to study effects of gravitational
      condition on organ development of the neonatal rat in this study. Eight-day old
      and 14-day old Sprague-Dawley rats were flown for 16 days on the Space Shuttle
      Columbia (April 17-May 3, 1998). The organs were weighed and the ratio of the
      organ weight to the body weight (organ weight ratio; OBR) was calculated. Tissues
      were analyzed using anatomical, immunohistochemical and molecular biological
      technique. Six animals of the 8-day old group were reared on the ground for 30
      more days after landing. The differences between flight and control rats in 8-day
      group were drastic. The lung, heart, kidney and adrenal glands in flight rats
      were significantly larger than that of control rats in OBR comparison. However,
      only the lung and kidney were still larger after 30 more days on ground. The
      kidney in flight rats performed pelvis expansion with down-regulation of
      aquaporin-2 expression confirmed by immunohistochemistry. The thymus, spleen,
      mesentery and pancreas were smaller in OBR. But the thymus in flight rats was
      heavier after 30 more days. The organs in flight rats which had no differences in
      OBR showed normal characteristics in histological analysis. We also found that
      the number of unmyelinated fibers of the aortic nerve in flight rats of 8-day
      group was smaller than that in control rats. In flight rats of the 14-day group,
      only the kidney was heavier and the ovary was lighter as compared to the
      controls. These results implied the second week of life was important for
      development during spaceflight. And the sensitivity and the critical period on
      neonatal development under microgravity might differ in each organ.

PMID- 15858354
TI  - Responses of neuromuscular systems under gravity or microgravity environment.
AB  - Hindlimb suspension of rats induces induces fiber atrophy and type shift of
      muscle fibers. In contrast, there is no change in the cell size or oxidative
      enzyme activity of spinal motoneurons innervating muscle fibers. Growth-related
      increases in the cell size of muscle fibers and their spinal motoneurons are
      inhibited by hindlimb suspension. Exposure to microgravity induces atrophy of
      fibers (especially slow-twitch fibers) and shift of fibers from slow- to fast
      twitch type in skeletal muscles (especially slow, anti-gravity muscles). In
      addition, a decrease in the oxidative enzyme activity of spinal motoneurons
      innervating slow-twitch fibers and of sensory neurons in the dorsal root ganglion
      is observed following exposure to microgravity. It is concluded that
      neuromuscular activities are important for maintaining metabolism and function of
      neuromuscular systems at an early postnatal development and that gravity effects
      both efferent and afferent neural pathways.

PMID- 15858355
TI  - Life history of amphibians and gravity.
AB  - Anurans hold a unique position in vertebrate phylogeny, as they made the major
      transition from water to land. Through evolution they have acquired fundamental
      mechanisms to adapt to terrestrial gravity. Such mechanisms are now shared among
      other terrestrial vertebrates derived from ancestral amphibians. Space research,
      using amphibians as a model animal, is significant based on the following
      aspects: (1) Anuran amphibians show drastic changes in their living niche during
      their metamorphosis. Environments for tadpoles and for terrestrial life of frogs
      are quite different in terms of gravity and its associated factors. (2) Certain
      tadpoles, such as Rhacophorus viridis amamiensis, have a transparent abdominal
      wall. Thus visceral organs and their motion can be observed in these animals in
      non-invasive manner through their transparent abdominal skin. This feature
      enables biologists to evaluate the physiological state of these amphibians and
      study the autonomic control of visceral organs. It is also feasible for space
      biologists to examine how such autonomic regulation could be altered by
      microgravity and exposure to the space environment.

PMID- 15858356
TI  - Vestibulo-ocular reflex and gravity in fish.
AB  - An otolith organ on ground behave as a detector of both gravity and linear
      acceleration, and play an important role in controlling posture and eye movement
      for tilt of the head or translational motion. On the other hand, a gravitational
      acceleration ingredient to an otolith organ disappears in microgravity
      environment. However, linear acceleration can be received by otolith organ and
      produce a sensation that is different from that on Earth. It is suggested that in
      microgravity signal from the otolith organ may cause abnormality of posture
      control and eye movement. We examined function of otolith organ in goldfish
      revealed from analysis of eye movement induced by linear acceleration. We
      analyzed vertical eye movements from video images frame by frame. In normal fish,
      leftward lateral acceleration induced downward eye rotation in the left eye and
      upward eye rotation in the right eye. Acceleration from caudal to rostra1 evoked
      downward eye rotation in both eyes. When the direction of acceleration was
      shifted 15 degrees left, the responses in the left eye disappeared. These results
      suggested that otolith organs in each side transmitted different signals.

PMID- 15858357
TI  - Radiation response mechanisms of the extremely radioresistant bacterium
      Deinococcus radiodurans.
AB  - Effect of microgravity on recovery of bacterial cells from radiation damage was
      examined in IML-2, S/MM-4 and S/MM-9 experiments using the extremely
      radioresistant bacterium Deinococcus radiodurans. The cells were irradiated with
      gamma rays before the space flight and incubated on board the Space Shuttle. The
      survival of the wild type cells incubated in space increased compared with the
      ground controls, suggesting that the recovery of this bacterium from radiation
      damage was enhanced under the space environment. No difference was observed
      between the survivals of radiosensitive mutant rec30 cells incubated in space and
      on the ground. The amount of DNA-repair related RecA protein induced under
      microgravity was similar to those of ground controls, however, induction of PprA
      protein, product of a unique radiation-inducible gene (designated pprA)
      responsible for loss of radiation resistance in repair-deficient mutant, KH311,
      was enhanced under microgravity compared with ground controls. Recent
      investigation in vitro showed that PprA preferentially bound to double-stranded
      DNA carrying strand breaks, inhibited Escherichia coli exonuclease III activity,
      and stimulated the DNA end-joining reaction catalyzed by DNA ligases. These
      results suggest that D. radiodurans has a radiation-induced non-homologous end
      joining (NHEJ) repair mechanism in which PprA plays a critical role.

PMID- 15858358
TI  - What kind of eye movements will goldfish show in space?
AB  - Six goldfish (1 normal, 1 with otoliths removed on both sides, 4 with otoliths
      removed on one side) were flown in space. The behaviors of the fish were recorded
      with a video camera on Mission Elapsed Time (MET) Day-00, 02, 05, 08, and 12. On
      MET Day-00, fish with otoliths removed on one side showed rolling behavior toward
      the operated side. No rolling behaviors were observed after MET Day-8. Five fish
      showed backward looping behaviors during the mission. After the space experiment,
      torsional eye movements and vertical eye movements were examined by body tilting.
      The experiments showed that the sensitivity of eye movements were low for head up
      tilting and tilting to operated side.

PMID- 15858359
TI  - Ten years after medaka fish mated and laid eggs in space and further preparation
      for the life-cycle experiment on ISS.
AB  - In the second International Microgravity Laboratory (IML-2/STS-65) mission in
      1994, medaka fish (Oryzias latipes) performed their successful mating behavior in
      space for the first time among vertebrate animals. The eggs the fish laid in
      space developed normally, and hatched as fry (baby fish) in space. Those fry born
      in space had the same number of germ cells as the ground control fish, and these
      germ cells later developed to produce the offspring on the ground. Fry hatched in
      space did not exhibit any looping behavior regardless of their strain, visual
      acuity, etc. For fish, one of the most exciting experiments to be done abroad the
      International Space Station (ISS) is a realization of fish life cycles in
      microgravity. At present, fish are the most likely candidates to be the first
      vertebrate to live their life cycle in space. Research done in our laboratory for
      realizing the life-cycle experiment of medaka fish are also introduced.

PMID- 15858360
TI  - Experiment facilities for life science experiments in space.
AB  - To perform experiments in microgravity environment, there should be many
      difficulties compared with the experiments on ground. JAXA (Japan Aerospace
      Exploration Agency) has developed various experiment facilities to perform life
      science experiments in space, such as Cell Culture Kit, Thermo Electric
      Incubator, Free Flow Electrophoresis Unit, Aquatic Animal Experiment Unit, and so
      on. The first experiment facilities were flown on Spacelab-J mission in 1992, and
      they were improved and modified for the 2nd International Microgravity Laboratory
      (IML-2) mission in 1994. Based on these experiences, some of them were further
      improved and flown on another missions. These facilities are continuously being
      improved for the International Space Station use, where high level functions and
      automatic operations will be required.

PMID- 15858361
TI  - Development of nitrogen-removal bioreactor using poly(lactic acid) as an energy
      source.
AB  - To control nitrogen such as ammonia in a rearing water of aquatic animals, we
      developed new bioreactor capable of both nitrification and denitrification. It
      was consisted of gel-plate immobilized microorganisms and a biodegradable plastic
      plate composed of three kind of poly(lactic acid) as an energy source of
      denitrification. When batch treatment experiment by the bioreactor was
      continuously carried out with an artificial rearing water containing ammonia,
      nitrogen-removal rate of the bioreactor was approximately 3 g-N/d/m2-gel surface
      and the activity was maintained for over 3 month without additional energy
      source. Therefore, the bioreactor would be effective to control nitrogen
      concentration in rearing water of a closed water circulating system for aquatic
      animals.

PMID- 15858362
TI  - Detection of biosphere frontier by using phosphatase activity.
AB  - A wide variety of methods have been proposed to detect microbial activities, but
      most of them can be applied to limited categories of terrestrial organisms. We
      propose here to use phosphatase activity, which seems to be an essential
      catalytic activity for all the terrestrial organisms, and possibly for
      extraterrestrial organisms. We determined phosphatase activity in core samples,
      chimney samples, and sea water samples obtained in submarine hydrothermal systems
      located at Suiyo Seamount, Izu-Bonin Arc, and South Mariana. It was shown that
      phosphatase activity is one of possible biomarkers for extant life.

PMID- 15858363
TI  - Space biology class as part of science education programs for high schools in
      Japan.
AB  - Declining incentives and scholastic abilities in science class has been concerned
      in Japan. The Ministry of Education, Culture, Sports, Science and Technology
      encourages schools to cooperate with research institutions to raise student's
      interest in natural sciences. The Science Partnership Program (SPP) and the Super
      Science High-School (SSH) are among such efforts. Our short SPP course consists
      of an introductory lecture on space biology in general and a brief laboratory
      practice on plant gravitropism. Space biology class is popular to students,
      despite of the absence of flight experiments. We suppose that students are
      delighted when they find that their own knowledge is not a mere theory, but has
      very practical applications. Space biology is suitable in science class, since it
      synthesizes mathematics, physics, chemistry and many other subjects that students
      might think uninteresting.

PMID- 15858364
TI  - Cyclic stretch induced MAPK phosphorylation stronger than static stretch.
AB  - The environment for living organism in space has microgravity and/or hypergravity
      and/or any kind of mechanical stresses. Cellular response may differ from the
      variety of mechanical stress. Mitogen-activated protein kinases (MAPKs) pathway
      is related to various cellular events. In the present study it was investigated
      the serial measurement of MAPK phosphorylation using western-blotting analysis
      following with three types of cyclic stretch, static, 0.1 Hz and 0.25 Hz. The
      result was that induction of MAPK phosphorylation had peaks within 2 to 4 hours
      and attenuated, while induction of p38 phosphorylation in 0.1 Hz stretch had a
      peak at 6 hours later and the strongest. Thus, there might be differential
      cellular response depends upon the frequency of cyclic stretch .

PMID- 15858365
TI  - The change of HSP47, collagen specific molecular chaperone, expression in rat
      skeletal muscle may regulate collagen production with gravitational conditions.
AB  - It is well known that unloading of skeletal muscle with spaceflight leads
      skeletal muscle atrophy. However, it remains unclear how the extracellular matrix
      within the muscle and the connective tissues such as tendon and ligament respond
      to reduced mechanical load including microgravity, although they have been
      thought to play important roles in both the transmission of force and the signal
      transduction between cells and tissues. Type-I collagen and type-IV collagen,
      both of the major components of extracellular matrix and connective tissues. We
      focused on change of these collagen synthesis with mechanical load. To obtain an
      insight into the effects of gravitational changing on the protein metabolism of
      collagen in skeletal muscle during mechanical unloading, reloading after
      unloading, we investigated changes in the amount of Heat shock protein 47
      (HSP47), has been postulated to be a collagen-specific molecular chaperone
      localized in the ER (Nagata et al, 1992). Western blot analysis revealed that
      HSP47 in rat soleus muscle decreases at 5 days after hindlimb suspension (HS). On
      the other hand, HSP47 in rat soleus muscle increases at 5 days after hypergravity
      (HG) induced by the centrifugation. RT-PCR analysis showed HSP47 mRNA decreased
      with HS earlier, as compared with collagen type-I and type-IV mRNA. From these
      results, the amount of HSP47 changing by gravitational condition may effect on
      signal transfers in the primary stage of adaptation and the change of HSP47
      expression in skeletal muscle may regulate collagen production with gravitational
      conditions.

PMID- 15858366
TI  - Global and temporal regulation of gene expression in Xenopus kidney cells in
      response to presumed microgravity generated by 3D clinostats.
AB  - We documented changes in morphology and gene expression of the renal epithelial
      cell line A6 derived from Xenopus leavis adult kidney induced by long-term
      culturing with three dimensional clinostats. An oligo microarray analysis on A6
      cells showed that mRNA levels of 52 out of 8091 genes were significantly altered
      in response to clinorotation. Upregulation or downregulation of gene expression
      became evident on day 8 and day 10 while there was no significant change on day
      5. However, on day 15, expression of 18 out of 52 genes resumed to the levels
      similar to its original levels while remaining 33 genes maintained altered levels
      of expression. Quantitative analyses of gene expression by real-time PCR
      confirmed that changes in mRNA levels of selected genes were found only under
      clinorotation but not under hypergravity (7 G) and ground control (1 G).
      Morphological changes including loss of dome-like structures, disassembly of E
      cadherin adherence junctions and disassembly of cortical actin were also observed
      over 10 days of culturing with clinorotation. The results revealed genes which
      expression was altered specifically in A6 cells cultured under clinorotation.

PMID- 15858367
TI  - Germination of white radish, buckwheat and qing-geng-cai under low pressure in
      closed environment.
AB  - In order to cultivate plants under low pressure in closed environment, the
      germination rate of seeds of white radish was investigated under low pressure,
      low oxygen partial pressure and condition of pure oxygen. The result of these
      experiments showed that the germination rate was affected by the oxygen partial
      pressure. From this fact, it is possible to lower the total pressure by using
      only the pure oxygen in germination. Furthermore, the germination rates of seeds
      of buckwheat and qing-geng-cai were also investigated in pure oxygen for the
      comparison. Consequently, though tendency in germination rate of white radish was
      similar to qing-geng-cai, it was different from buckwheat.

PMID- 15858368
TI  - Gravity-regulated proteins of Arabidopsis and cucumber seedlings detected by 2-D
      electrophoresis.
AB  - Gravity exerts a profound influence on plant growth. Proteomics may be the most
      promising technique to identify the proteins that are induced, repressed, or post
      transcriptionally modified during gravity response in plants. In this research,
      the model plant, Arabidopsis grown in stationary and clino-rotated condition for
      7 to 10 days and cucumber plant with the unique gravimorphogenesis were used.
      Namely, cucurbit seedlings develop a peg on the transition zone between the
      hypocotyls and root. Cucumber seedlings grown in a horizontal position on the
      ground suppress the development of the peg (negatively-controlled) on the upper
      side of the transition zone in response to gravity. Then, we analyzed gravity
      regulated proteins expression by two-dimensional (2-D) gel electrophoresis.

PMID- 15858369
TI  - Is water immersion useful for analyzing gravity resistance responses in
      terrestrial plants?
AB  - Water immersion has been used as a simulator of microgravity for analyzing
      gravity responses in semiaquatic plants such as rice. To examine whether or not
      water immersion for a short experimental period is a useful microgravity
      simulator even in terrestrial plants, we analyzed effects of water immersion on
      the cell wall rigidity and metabolisms of its constituents in azuki bean
      epicotyls. The cell wall rigidity of epicotyls grown underwater was significantly
      lower than that in the control. Water immersion also caused a decrease in
      molecular mass of xyloglucans as well as the thinning of the cell wall. Such
      changes in the mechanical and chemical properties of the cell wall underwater
      were similar to those observed in microgravity conditions in space. These results
      suggest that water immersion for a short period is a useful system for analyzing
      gravity resistance responses even in terrestrial plants.

PMID- 15858370
TI  - Effects of hypergravity environment on lignin formation in Arabidopsis.
AB  - Lignin and the secondary wall formation are essential for evolution of land
      plants. In this study, effects of hypergravity environment on the morphology of
      the secondary wall and the lignin content were examined in Arabidopsis thaliana.
      Xylem vessels showed intense staining with phloroglucinol-HCl and
      autofluorescence under UV light at the basal region of the flower stalk when
      seedlings grown for 3 days after hypergravity treatment for 24 hours. And, the
      flower stalk exposed to hypergravity showed slight increase in the lignin
      content. These results suggest that the lignin formation is positively regulated
      under hypergravity.

PMID- 15858371
TI  - Effect of hypergravity stimulus on XTH gene expression in Arabidopsis thaliana.
AB  - Hypergravity stimulus suppresses plant shoot growth by making the cell wall
      rigid. Xyloglucan endotransglucosylase/hydrolase (XTH) is involved in determining
      the rigidity of cell walls. We demonstrated that hypergravity influenced the
      expression of some XTH genes in shoots of Arabidopsis thaliana L.; in response to
      hypergravity stimulus of 300 g, the expression of AtXTH22 was up-regulated, while
      that of AtXTH15 was down-regulated. The effect of hypergravity on the expression
      of these genes was nullified by lanthanum chloride at 0.1 mM, suggesting that the
      expression of these XTH genes in Arabidopsis is under the control of the
      mechanoreceptor.

PMID- 15858372
TI  - Lily pistils bend toward light.
AB  - Flower shape shows up and down features in many cases. Pistils of lily flower,
      Lilium cv. 'Casablanca', bend upward by sensing exclusively light. There found no
      sediment amyloplast in pistil corresponding to the absence of gravitropism. Fine
      granules of amyloplast disappear from pistil and tepal after opening of flower,
      except stomatal guard cells distributed on their epidermis. Bending of pistil
      caused by phototropism occurs when rate of its local elongation passes maximum
      and decreases. Elongation of pistil starts from its basal part close to ovary,
      and propagate toward distal tip afterwards. Bending of pistil follows this
      propagation. Because of this feature, curvature of pistil tends to be rather
      steep at the basal part. From spot irradiation experiment, site of sensing light
      was found not spatially separated by twice of diameter from site of bending.

PMID- 15858373
TI  - Distribution of L-DOPA in the root of velvet bean plant (Mucuna pruriens L.) and
      gravity.
AB  - Velvet bean (Mucuna pruriens L.) has been found that the degree of suppression on
      the lettuce root growth by velvet bean was less on the 3D-clinorotation. The
      number and growth of adventitious root in velvet bean differed among the
      clinostated and control group. L-DOPA (L-3,4-dihydroxyphenylalanine) is known to
      be the major substance in the allelopathy of velvet bean plant, released from its
      root. Since L-DOPA is a precursor of melanin pigment, and is easily converted to
      melanin by oxidation, locality of L-DOPA production in the plant body can be seen
      through pigmentation. The amount of L-DOPA was analyzed by HPLC and LC-ESI/MS.
      The distribution of L-DOPA in the root was different among the ground control
      condition and pseudo-microgravity.

PMID- 15858374
TI  - Modulation of cell mutability by serum factors from volunteers who experienced
      head-down-tilt bed rest.
AB  - Head-down-tilt bed rest (BR) is utilized to mimic a microgravity environment. In
      this study, we examined whether the modulating activity of serum factors on cell
      mutability was changed in seventeen volunteers subjected to BR. For comparison,
      serum was comparatively obtained from seven volunteers who experienced the
      parabolic flight (PF). Cultured human cells were treated with serum and then
      irradiated with UV or X-ray. Mutagenicity was estimated by identification of K
      ras codon 12 base substitution mutation, following PCR and differential dot-blot
      hybridization. Modulating activity was detected in one sample from each of post
      BR and post-PF serum.

PMID- 15858375
TI  - A proposal on a contribution of space biological sciences to sexual health in the
      human space life.
AB  - Sexuality is a basic property of the human being and provides an important
      background for the human life and society. The present situation in the world
      strongly suggests that the human being will extensively and intensively spread
      out in space and the population in space, particularly on the space stations in
      orbit, moon and possibly Mars, will rapidly increase during this century.
      Therefore sexual health will become a serious issue for the development of space
      and a better life of the human in the space environment. It is not too early to
      consider sexuality in the space life and to discuss how to maintain sexual
      health, how to control it in the space society, or whether it should be
      controlled. Space biological sciences should be the key and play an important
      role in studying scientifically sexuality especially the sex, sexual behavior and
      reproduction in the space environment.

PMID- 15858376
TI  - Eye movements of goldfish depending on the relationship between acceleration
      vector and otolith organ.
AB  - Prior experiments demonstrated that the acceleration deviating 15 degrees to the
      right (left) from the longitudinal body axis could not produce vertical eye
      movement in left (right) eye of the goldfish. From these results, we expected
      that vertical eye movement of goldfish for the acceleration perpendicular to the
      longitudinal body axis might different between right and left eye. However, in
      this experiments, there were no clear difference in magnitude of vertical eye
      movements for the acceleration shifted 15 degrees around the left-right body
      axis. On the other hand, the response of right eye was larger than that of left
      eye for the acceleration applied from left to right of the body. These results
      suggest that stimulation from medial to lateral and lateral to medial of the
      otolith organ has different effect on vertical eye movement in each eye of
      goldfish.

PMID- 15858377
TI  - Cell proliferation of Paramecium tetraurelia under clinorotation.
AB  - It has been reported that Paramecium proliferates faster under microgravity in
      space, and slower under hypergravity (Kato et al., 2003). Effects of gravity on
      cell proliferation could be discussed in terms of energetics of swimming. Because
      of the characteristics of 'gravikinesis' as well as 'gravitaxis', Paramecium
      would decrease the energy expenditure under microgravity and increase it under
      hypergravity. The larger stock of energy would enhance the proliferation under
      microgravity. In order to simulate the effect of microgravity, we investigated
      the proliferation under clinorotation. When cells were rotated at 2.5 rpm, the
      proliferation rate decreased. Similar but less pronounced decrease was also found
      under low speed clinorotation (0.2 rpm).

PMID- 15858378
TI  - Relationship between the stress of hyper-gravity and food intake and growth rate
      in mouse.
AB  - A new method was introduced to assess the effects of hyper-gravity on secretion
      of corticosterone, one of the major stress hormone, in mouse. The hormone was
      extracted from feces of the animal and measured by means of ELISA. The amount of
      corticosterone was high at the beginning of breeding under the hyper-gravity, 3
      G. It decreased down to the level of the ground control within 2 weeks. Increases
      both in the growth rate of the body weight and the food intake were closely
      related to the decrease in the amount of corticosterone. It is likely that hyper
      gravity affects the growth rate via internal secretion.

PMID- 15858379
TI  - HZE radiation effects for hereditary renal carcinomas.
AB  - Eker rat known as a model of hereditary renal carcinoma (RC) is an example of
      Mendelian dominantly inherited predisposition to a specific cancer in
      experimental animals. We investigate the effects of simulated space radiation on
      carcinogenesis using HIMAC. We estimated RBE from the Eker rats exposed to the
      heavy-ions, C (290 MeV/u) and Fe (500 MeV/u) ions, comparing to the effects of X
      ray irradiation. Pregnant rats were exposed to C and Fe ions and X-rays with a
      single dose of 1 Gy, 2 Gy, 3 Gy on day 19 of gestation. The offspring were
      sacrificed at 8 weeks of age. We evaluated organ weights and tumor genesis. The
      weights of thymus, lung, liver, spleen were found to be no difference from the
      control at 1 Gy irradiation but 50% decrease at 3 Gy irradiation. We found in the
      irradiated animal that kidney, brain and testis were very sensitive organs of
      which the weight decreased to approximately 80% at 1 Gy and to 40% at 3 Gy
      irradiations. Based on the dose-response relationship of the radiation-induced
      carcinoma, averaged RBE ware calculated to be 1.1 for C-ion, 1.6 for Fe-ion.

PMID- 15858380
TI  - Formation and stability of complex organic compounds in space environments.
AB  - Complex organic compounds have been found in extraterrestrial bodies such as
      meteorites and comets. We confirmed the formation of complex organic compounds
      that contained amino acid precursors from a mixture of carbon monoxide (or
      methanol), ammonia and water by radiation or UV. Molecular weights of the complex
      organics were several thousands. Stability of the complex precursors was studied.
      When free amino acids were irradiated with gamma rays or synchrotron radiation,
      they easily decomposed. The complex precursors were, however, much more stable
      than free amino acid against irradiation. We propose to examine the formation and
      alteration of amino acid precursors in space by using exposed facility of ISS.

PMID- 15858381
TI  - C-fos expression of osteoblast-like MC3T3-E1 cells induced either by cooling or
      by fluid flow.
AB  - Fluid flow is one of the most potent mechanical stimulators for bone cells.
      Recent reports suggest that primary cilia as well as ion channels and related
      molecules play roles in the flow detection by kidney epithelial cells. We asked
      if there is any commonality between kidney and bone cells in flow detection.
      Primary cilia of cultured osteoblastic cell line MC3T3-E1 were detected by
      fluorescence staining of acetylated alpha-tubulins. The cells responded to fluid
      flow, generated by manual rocking of flasks, and expressed c-fos gene. Moreover,
      the cells were found to respond not only the flow but also cooling of the culture
      fluid, with a simple technique to keep temperature precisely. It was suggested
      that bone and kidney cells might share certain similarity in flow detection
      mechanisms.

PMID- 15858382
TI  - Relationship between the visiting birds and nectar secretion in the cherry tree.
AB  - The flying birds to cherry tree, Prunus campanulata, are well known. However
      since their relationship has not yet been examined, then the present study
      elucidated their relationship at Tama Forestry and Forest Product Research
      Institute. The observation of flying birds was carried out on their species,
      number, attitude and visiting time, with naked eye, a video camera, and a camera
      from the blind. The observations were carried out every 15 minutes during 5 to 12
      hours per day. The efflorescence grade was divided into 4 stages. Bulbul visited
      most frequently to the tree among visiting birds, on the other hand white-eye
      visited hardly due to the disturbance by bulbul. The nectar grade gradually
      increased together with the efflorescence grade, then reached 30% at the 4th
      stage.

PMID- 15858383
TI  - Expression of gibberellin biosynthetic gene in Japanese weeping cherry.
AB  - The expressions of gibberellin (GA) biosynthetic gene in both of the upright and
      the weeping types of Japanese flowering cherry (Prunus spachiana) were
      investigated. A part of the GA 3-beta hydroxylase gene of Prunus spachiana
      (Ps3bhx), which synthesizes active GAs, were amplified by real-time RT-PCR
      technique. The accumulation of Ps3bhx mRNA in the weeping type were much more
      than that in the upright type.

PMID- 15858384
TI  - System of cell irradiation with a defined number of heavy ions (III).
AB  - A single cell irradiation system has been developed at JAERI-Takasaki to study
      radiobiological processes in single-ion-hit mammalian cells and bystander cells,
      in ways that cannot be achieved using conventional broad field exposures.
      Individual mammalian cultured cells are irradiated in the atmosphere on the cell
      dish, the bottom of which is made of ion-track-detector CR-39, with a single or
      defined numbers of 13.0 MeV/amu 20Ne and 11.5 MeV/amu 40Ar ions. Targeting and
      irradiation of the cells are performed automatically at the on-line microscope of
      the microbeam apparatus according to the positional data of the target cells
      obtained at the off-line microscope before irradiation. Using this system,
      Chinese hamster ovary (CHO-K1) cells were irradiated with counted number of 20Ne
      and 40Ar ions. Thereafter, the growth of the cells was observed individually and
      repeatedly during post-irradiation incubation. The cells hit by a single 40Ar ion
      on their nucleus showed strong growth inhibition. Meanwhile, the cells in the
      irradiated dish but not hit by the ion (bystander cells) showed limited cell
      growth. This might be a bystander effect caused by heavy ion hit cell co-existing
      in the same dish.

PMID- 15858385
TI  - LET and ion-species dependence for mutation induction and mutation spectrum on
      hprt locus in normal human fibroblasts.
AB  - We have been studying LET and ion species dependence of RBE in mutation frequency
      and mutation spectrum of deletion pattern of exons in hprt locus. Normal human
      skin fibroblasts were irradiated with heavy-ion beams, such as carbon- (290 MeV/u
      and 135 MeV/u), neon- (230 MeV/u and 400 MeV/u), silicon- (490 MeV/u) and iron-
      (500 MeV/u) ion beams, generated by Heavy Ion Medical Accelerator in Chiba
      (HIMAC) at national Institute of Radiological Sciences (NIRS). Mutation induction
      in hprt locus was detected to measure 6-thioguanine resistant colonies and
      deletion spectrum of exons was analyzed by multiplex PCR. The LET-RBE curves of
      mutation induction for carbon- and neon-ion beams showed a peak around 75
      keV/micrometers and 155 keV/micrometers, respectively. On the other hand, there
      observed no clear peak for silicon-ion beams. The deletion spectrum of exons was
      different in induced mutants among different ion species. These results suggested
      that quantitative and qualitative difference in mutation occurred when using
      different ion species even if similar LET values.

PMID- 15858386
TI  - The biological effects of space radiation during long stays in space.
AB  - Many space experiments are scheduled for the International Space Station (ISS).
      Completion of the ISS will soon become a reality. Astronauts will be exposed to
      low-level background components from space radiation including heavy ions and
      other high-linear energy transfer (LET) radiation. For long-term stay in space,
      we have to protect human health from space radiation. At the same time, we should
      recognize the maximum permissible doses of space radiation. In recent years,
      physical monitoring of space radiation has detected about 1 mSv per day. This
      value is almost 150 times higher than that on the surface of the Earth. However,
      the direct effects of space radiation on human health are currently unknown.
      Therefore, it is important to measure biological dosimetry to calculate relative
      biological effectiveness (RBE) for human health during long-term flight. The RBE
      is possibly modified by microgravity. In order to understand the exact RBE and
      any interaction with microgravity, the ISS centrifugation system will be a
      critical tool, and it is hoped that this system will be in operation as soon as
      possible.

PMID- 15858387
TI  - Clustered DNA damage induced by heavy ion particles.
AB  - Clustered DNA damage (locally multiply damaged site) is thought to be a critical
      lesion caused by ionizing radiation, and high LET radiation such as heavy ion
      particles is believed to produce high yields of such damage. Since heavy ion
      particles are major components of ionizing radiation in a space environment, it
      is important to clarify the chemical nature and biological consequences of
      clustered DNA damage and its relationship to the health effects of exposure to
      high LET particles in humans. The concept of clustered DNA damage emerged around
      1980, but only recently has become the subject of experimental studies. In this
      article, we review methods used to detect clustered DNA damage, and the current
      status of our understanding of the chemical nature and repair of clustered DNA
      damage.

PMID- 15858388
TI  - Chromosome aberrations induced by high-LET radiations.
AB  - Measurements of chromosome aberrations in peripheral blood lymphocytes are
      currently the most sensitive and reliable indicator of radiation exposure that
      can be used for biological dosimetry. This technique has been implemented
      recently to study radiation exposures incurred by astronauts during space flight,
      where a significant proportion of the dose is delivered by high-LET particle
      exposure. Traditional methods for the assessing of cytogenetic damage in mitotic
      cells collected at one time point after exposure may not be suitable for
      measuring high-LET radiation effects due to the drastic cell cycle perturbations
      and interphase cell death induced by this type of exposure. In this manuscript we
      review the recent advances in methodology used to study high-LET induced
      cytogenetic effects and evaluate the use of chemically-induced Premature
      Chromosome Condensation (PCC) as an alternative to metaphase analysis. Published
      data on the cytogenetic effects of in vitro exposures of high-LET radiation is
      reviewed, along with biodosimetry results from astronauts after short or long
      space missions.

PMID- 15858389
TI  - Mutations induced by heavy charged particles.
AB  - The relative biological-effectiveness of radiation is increased when cells or
      tissue are exposed to densely ionizing (high-LET) radiation. A large number of
      studies focus on the following aspects of the biological effects of high-LET
      radiation: (i) basic understanding of radiation damage and repair; (ii)
      developing radiotherapy protocols for accelerated charged particles; and (iii)
      estimation of human risks from exposure to high-LET heavy charged particles. The
      increased lethal effectiveness (cell inactivation) of high-LET radiation
      contributes to new methods for using radiation therapy, but it is also necessary
      to study the enhanced mutagenic effect of high LET radiation, because higher
      frequencies of mutation can be expected to provide higher rates of
      carcinogenicity with human exposure. It is important to note that both measures
      of biological effectiveness (lethality and mutagenicity) depend on the quality of
      radiation, the dose, dose-rate effects, and the biological endpoints studied.
      This paper is intended to provide a review of current research on the mutagenic
      effects of high-LET radiation, and is organized into three sections. First, are
      descriptions of the induced mutations studied with various detection systems
      (section 1) because the detectable mutations induced by ionizing radiation,
      including heavy-ions, depend largely on the detection system used. Second is a
      discussion of the biological significance of the dependence of induced mutations
      on LET (section 2). This is related to the molecular nature of radiation lesions
      and to the repair mechanisms used to help cells recover from such damage.
      Finally, applications of mutation detection systems for studies in space (section
      3) are described, in which the carcinogenic effects of space environmental
      radiation are considered.

PMID- 15858390
TI  - Microbeams of heavy charged particles.
AB  - We have established a single cell irradiation system, which allows selected cells
      to be individually hit with defined number of heavy charged particles, using a
      collimated heavy-ion microbeam apparatus at JAERI-Takasaki. This system has been
      developed to study radiobiological processes in hit cells and bystander cells
      exposed to low dose and low dose-rate high-LET radiations, in ways that cannot be
      achieved using conventional broad-field exposures. Individual cultured cells
      grown in special dishes were irradiated in the atmosphere with a single or
      defined numbers of 18.3 MeV/amu 12C, 13.0 MeV/amu 20Ne, and 11.5 MeV/amu 40Ar
      ions. Targeting and irradiation of the cells were performed automatically at the
      on-line microscope of the microbeam apparatus according to the positional data of
      the target cells obtained at the off-line microscope before irradiation. The
      actual number of particle tracks that pass through cell nuclei was detected with
      prompt etching of the bottom of the cell dish made of ion track detector TNF-1
      (modified CR-39), with alkaline-ethanol solution at 37 degrees C for 15-30
      minutes. Using this system, separately inoculated Chinese hamster ovary cells,
      confluent normal human fibroblasts, and single plant cells (tobacco protoplasts)
      have been irradiated. These are the first studies in which single-ion direct hit
      effect and the bystander effect have been investigated using a high-LET heavy
      particle microbeam.

PMID- 15858391
TI  - Heavy charged particles produce a bystander effect via cell-cell junctions.
AB  - Radiation-induced damage to living cells results from either a direct hit to
      cellular DNA, or from indirect action which leads to DNA damage from radiation
      produced radicals. However, in recent years there is evidence that biological
      effects such as cell killing, mutation induction, chromosomal damage and
      modification of gene expression can occur in a cell population exposed to low
      doses of alpha particles. In fact these doses are so low that not all cells in
      the population will be hit directly by the radiation. Using a precision alpha
      particle microbeam, it has been recently demonstrated that irradiated target
      cells can induce a bystander mutagenic response in neighboring "bystander" cells
      which were not directly hit by alpha particles. Furthermore, these results
      suggest that gap-junction mediated cell-to-cell communication plays a critical
      role in this bystander phenomenon. The purpose of this section is to describe
      recent studies on bystander biological effects. The recent work described here
      utilized heavy charged particles for irradiation, and investigated the role of
      gap-junction mediated cell-cell communication in this phenomenon.

PMID- 15858392
TI  - Radiation-induced adaptive responses and bystander effects.
AB  - A classical paradigm [correction of paradym] of radiation biology asserts that
      all radiation effects on cells, tissues and organisms are due to the direct
      action of radiation. However, there has been a recent growth of interest in the
      indirect actions of radiation including the radiation-induced adaptive response,
      the bystander effect, low-dose hypersensitivity, and genomic instability, which
      are specific modes of stress exhibited in response to low-dose/low-dose rate
      radiation. This review focuses on the radiation-induced bystander effect and the
      adaptive response, provides a description of the two phenomena, and discusses the
      contribution of the former to the latter.

PMID- 15858393
TI  - The significance of the study about the biological effects of solar ultraviolet
      radiation using the Exposed Facility on the International Space Station.
AB  - It is believed that ultraviolet (UV) radiation from the sun participated in
      events related to the chemical evolution and birth of life on the primitive
      Earth. Although UV radiation would be also a driving force for the biological
      evolution of life on Earth, life space of the primitive living organisms would be
      limited in the UV-shielded place such as in the water at an early stage of the
      evolution of life. After the formation of stratospheric ozone layer through the
      production of oxygen by photoautotroph, living organisms were able to expand
      their domain from water to land. As a result, now, many kinds of living organisms
      containing human beings are flourishing on the ground. In the near future,
      increased transmission of harmful solar UV radiation may reach the Earth's
      surface due to stratospheric ozone layer depletion. In order to learn more about
      the biological effects of solar UV radiation with or without interruption by the
      ozone layer, the utilization of an Exposed Facility on the International Space
      Station is required. Experiments proposed for this facility would provide a tool
      for the scientific investigation of processes involved in the birth and evolution
      of life on Earth, and could also demonstrate the importance of protecting the
      Earth's future environment from future ozone layer depletion.

PMID- 15858394
TI  - Expression of gibberellin 3 beta-hydroxylase gene in a gravi-response mutant,
      weeping Japanese flowering cherry.
AB  - Expressions of the gibberellin biosynthesis gene were investigated in a normal
      upright type and a gravi-response mutant, a weeping type of Japanese flowering
      cherry (Prunus spachiana), that is unable to support its own weight and elongates
      downward. A segment of the gibberellin 3 beta-hydroxylase cDNA of Prunus
      spachiana (Ps3ox), which is responsible for active gibberellin synthesis, was
      amplified by using real-time RT-PCR. The content of Ps3ox mRNA in the weeping
      type was much greater than that in the upright type, while the endogenous
      gibberellin level was much higher in the elongating zone of the weeping type.
      These results suggest that the amount and distribution of synthesized gibberellin
      regulate secondary xylem formation, and the unbalanced distribution of
      gibberellin affects the gravi-response of the Prunus tree.

PMID- 15858395
TI  - Calcium channel blockers: a more expansive treatment role.

PMID- 15858396
TI  - The role of calcium antagonists in stroke prevention.
AB  - Lowering elevated blood pressure significantly reduces the risk of stroke, but
      whether any specific type of antihypertensive medication is better for this
      purpose, independent of blood pressure-lowering effects, is controversial.
      Compared with placebo or no treatment, the point estimate for stroke reduction is
      the largest with calcium antagonists; all such studies used dihydropyridine
      compounds. When all clinical trials published through December 2004 are combined
      in meta-analysis, stroke is not significantly reduced when an initial
      dihydropyridine or nondihydropyridine calcium antagonist is compared with an
      initial diuretic or beta blocker, but when the two subclasses are combined,
      stroke reduction (9%) is significant. The risk of heart failure, however, is
      significantly increased (by 29%) with the initial calcium antagonist. These
      estimates may change as newer trials are reported.

PMID- 15858397
TI  - Therapeutic considerations in the African-American patient with hypertension:
      considerations with calcium channel blocker therapy.
AB  - African Americans have a higher prevalence, earlier onset, and more rapid
      progression of hypertensive end-organ disease, as well as excessive hypertensive
      mortality compared with other racial/ethnic groups. Most differences in
      hypertension and pressure-related complications between African Americans and
      whites appear to be quantitative and not qualitative. Improving the diagnosis,
      treatment, and control of hypertension in this highly vulnerable population is a
      major health care goal for the new millennium. In this regard the dietary pattern
      to be promoted for reduction of hypertension risk in African Americans is one of
      increased consumption of dairy products, fruit, and vegetables as well as a
      continued emphasis on decreased Na+ intake. When pharmacologic therapy is
      considered, multi-drug approaches are generally required, with diuretics,
      angiotensin-converting enzyme inhibitors (or angiotensin receptor blockers), and
      calcium channel blocker therapy as oft-selected components of most such treatment
      regimens.

PMID- 15858398
TI  - Management of hypertensive chronic kidney disease: role of calcium channel
      blockers.
AB  - Both the prevalence and incidence of end-stage renal disease have been increasing
      in the United States over the past two decades. Diabetes and hypertension are the
      attributable causes for more than three fourths of all new cases of end-stage
      renal disease. The overwhelming majority of diabetics with nephropathy are
      hypertensive, and lowering blood pressure is indicated in all patients with
      chronic kidney disease because of the increased risk for cardiovascular morbidity
      and mortality. Multiple studies indicate that reaching goal systolic blood
      pressure in patients with chronic kidney disease generally requires three to four
      antihypertensive agents. A number of medication combinations can effectively
      reduce blood pressure in the chronic kidney disease patient. In this regard,
      adding a calcium channel blocker to an angiotensin-converting enzyme inhibitor or
      an angiotensin receptor blocker helps in reaching goal blood pressure while
      preserving renal function in both diabetics and nondiabetics with proteinuria.

PMID- 15858399
TI  - Calcium channel blocker class heterogeneity: select aspects of pharmacokinetics
      and pharmacodynamics.
AB  - Calcium channel blockers (CCBs) comprise a heterogeneous group of compounds with
      unique structures and pharmacologic characteristics. These agents are employed in
      the treatment of hypertension, coronary ischemia, and/or supraventricular
      arrhythmias. CCBs are both substrates for, and in the instance of verapamil and
      diltiazem inhibitors of, cytochrome P450 3A4. In the case of verapamil and
      diltiazem, this inhibitory effect increases the likelihood of drug-drug
      interactions with other compounds similarly metabolized by cytochrome P450 3A4.
      Much of the debate with reference to a cardiovascular risk for CCBs has been
      quieted with the advent of sustained-release delivery systems that offer a more
      gradual rate of drug delivery. The most common side effects with CCBs are
      vasodilatory in nature and include peripheral edema, flushing, and headache.
      Despite the potential for side effects with CCBs, their potent blood pressure
      lowering effect makes them a prerequisite for blood pressure control in many
      patients.

PMID- 15858400
TI  - Comparison of blood pressure control with amlodipine and controlled-release
      isradipine: an open-label, drug substitution study.
AB  - An open-label drug substitution study showed that controlled-release isradipine
      (Dynacirc-CR) can be safely substituted for amlodipine on a mg-for-mg basis in
      patients with mild-to-moderate hypertension. When controlled-release isradipine
      was substituted for amlodipine, blood pressure was more effectively controlled,
      and edema rates were reduced. When subjects resumed amlodipine therapy, the
      previous gain in blood pressure reduction and lessening of edema vanished. The
      basis for this more favorable pattern of efficacy and side-effects with
      controlled-release isradipine, although mechanistically unresolved, may relate to
      a lesser degree of sympathetic nervous system activation.

PMID- 15858401
TI  - Spinal muscular atrophy: a delayed development hypothesis.
AB  - Spinal muscular atrophy is an inherited neuromuscular disorder. The gene
      responsible for the disease has been identified and named the SMN gene. This
      review is prompted by recent advances in understanding cellular function of the
      SMN gene and its gene product and by the increasing evidence that maturation of
      all parts of the neuromuscular system is delayed in spinal muscular atrophy
      patients. We suggest that the timing of developmental changes in motoneurons and
      muscles is critical for their survival. Delayed maturation of either motoneuron
      or muscle can cause these cells to die so the molecules that are involved in
      controlling their rate of maturation are crucial for normal development. We
      suggest that SMN gene/protein is one such molecule, because the neuromuscular
      system develops more slowly in spinal muscular atrophy patients, where SMN
      protein is absent, and in animals models, where SMN protein is reduced.

PMID- 15858402
TI  - Electroencephalography/magnetoencephalography study of cortical activities
      preceding prosaccades and antisaccades.
AB  - The temporal and spatial characteristics of brain activity preceding prosaccades
      and antisaccades were investigated using source reconstructions of 64-channel
      electroencephalography and 148-channel magnetoencephalography data. Stimulus
      locked data showed early cuneus activity was stronger during antisaccades, and
      later occipital gyrus activity was stronger preceding prosaccades, which suggests
      a top-down influence on early visual processing. Response-locked data showed that
      supplementary eye field, prefrontal cortex, and medial frontal eye field activity
      was greater for antisaccades than for prosaccades prior to saccade generation.
      Lateral frontal eye field activity appeared to be inhibited prior to antisaccade
      response generation. The spatial and temporal resolution of combined
      electroencephalography/magnetoencephalography data allows the evaluation of
      specific cortical activities preceding saccades and for demonstration of how
      activities differ as a function of response contingencies.

PMID- 15858403
TI  - Neural correlates of frustration.
AB  - Psychological considerations suggest that the omission of rewards in humans
      comprises two effects: first, an allocentric effect triggering learning and
      behavioural changes potentially processed by dopaminergic neurons according to
      the prediction error theory; second, an egocentric effect representing the
      individual's emotional reaction, commonly called frustration. We investigated
      this second effect in the context of omission of monetary reward with functional
      magnetic resonance imaging. As expected, the contrast omission relative to
      receipt of reward led to a decrease in ventral striatal activation consistent
      with prediction error theory. Increased activation for this contrast was found in
      areas previously related to emotional pain: the right anterior insula and the
      right ventral prefrontal cortex. We interpreted this as a neural correlate of the
      egocentric effect.

PMID- 15858404
TI  - Developmental expression patterns and localization of DNA-binding protein
      inhibitor (Id3) in the mouse retina.
AB  - Id3 (inhibitor of DNA binding/differentiation), a member of the Id helix-loop
      helix protein family, has long been studied as a positive regulator of
      proliferation and a negative regulator of differentiation. In this study, we
      examined the expression pattern and cellular phenotypes of Id3 in postnatal and
      adult mouse retina. Id3 was mainly expressed in the early postnatal inner retina.
      From the late postnatal development towards adulthood, Id3 expression was
      confined to the ganglion cell layer and the inner nuclear layer. Colocalization
      analysis showed that Id3 positive cells were identified as retinal ganglion cells
      and amacrine cells. The differential expression profiles of Id3 provide the
      groundwork for the elucidation of its possible role in retinal development.

PMID- 15858405
TI  - Antiganglion neuron antibodies correlate with neuropathy in Sjogren's syndrome.
AB  - To investigate the possible implication of antibodies against dorsal root
      ganglion neuron in the pathogenesis of sensory neuropathy with Sjogren's
      syndrome, we examined the pathogenic role of antiganglion neuron antibodies by
      immunoblotting, immunohistochemistry and immunoreactive assay. Sjogren's syndrome
      patients without neuropathy, patients with vasculitic neuropathy and normal
      volunteers were evaluated as controls. Antiganglion neuron antibodies recognizing
      certain proteins of several different molecular weights were detected only in
      patients of sensory neuropathy with Sjogren's syndrome. Those antibodies labeled
      specific-sized neurons in the fixed ganglion and isolated ganglion neurons under
      the culture condition, each of which corresponded well to clinical
      manifestations. These results suggest that antiganglion neuron antibodies may
      contribute to the pathogenesis of sensory neuropathy with Sjogren's syndrome.

PMID- 15858406
TI  - A modified parallel paradigm for clinical evaluation of auditory echoic memory.
AB  - We established a new parallel paradigm for mismatch negativity by presenting
      repetitive trains of three consonant-vowel syllables and those of three
      sinusoidal tones alternately. Magnetoencephalography was performed to test the
      new method, and mismatch negativities in six study participants with normal
      hearing were compared with the results of the conventional oddball paradigm. Peak
      amplitude and latencies of mismatch negativity showed no significant difference
      between the methods. The maximum amplitude in short memory probe interval of 1.0
      s was significantly larger than in long memory probe interval of 3.0 s,
      demonstrating decay in auditory echoic memory caused by a prolonged memory probe
      interval. The new method facilitated simultaneous evaluation of mismatch
      negativity with various stimuli in a shorter period.

PMID- 15858407
TI  - Serofendic acid promotes survival of auditory hair cells and neurons of mice.
AB  - Serofendic acid is a newly discovered neuroprotective substance derived from
      fetal calf serum. It has previously been shown to protect cortical neurons from
      the cytotoxicity of nitric oxide, glutamate and oxygen species. In the present
      study, we examined the protective effects of serofendic acid on auditory hair
      cells exposed to aminoglycoside toxicity using explant cultures of mouse auditory
      epithelia. We also determined the effect of serofendic acid on auditory neurons
      experiencing neurotrophin deprivation using primary cultures of mouse spiral
      ganglion neurons. Supplementation with serofendic acid significantly promoted the
      survival of auditory hair cells and neurons, and its protective effects were
      stronger than those of the caspase inhibitor z-VAD-fmk. These findings
      demonstrate the great potential of serofendic acid for protection of the auditory
      system.

PMID- 15858408
TI  - Transcranial magnetic stimulation of the sensorimotor cortex alters kinaesthesia.
AB  - Tendon vibration is known to evoke perception of illusory movements, together
      with motor responses in the muscles antagonistic to those vibrated. In the
      present study, we assessed the perceptual and motor effects of transcranial
      magnetic stimulation of the sensorimotor cortex during illusions of hand
      movements evoked by vibration of wrist muscle tendons. The results showed that
      transcranial magnetic stimulation could accelerate or decelerate the illusory
      movements, depending on the site and intensity of magnetic stimulation. Whenever
      transcranial magnetic stimulation decelerated illusory movements, motor responses
      decreased, whereas whenever it accelerated illusory movements, motor responses
      increased. We conclude that motor responses associated with movement illusions
      have a cortical stage, because they are affected by experimentally induced
      disruption of activity in intracortical networks.

PMID- 15858409
TI  - 8-hydroxy-2-(di-n-propylamino)tetralin reduces striatal glutamate in an animal
      model of Parkinson's disease.
AB  - Using in-vivo microdialysis, we examined the effect of the serotonin 5-HT1A
      agonist R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin on striatal extracellular
      excitatory amino acids in an animal model of Parkinson's disease. Extracellular
      glutamate and aspartate in the dopamine-denervated striatum of unilateral 6
      hydroxydopamine-lesioned rats were significantly decreased by acute subcutaneous
      injection of R-(+)-8-hydroxy-2-(di-n-propylamino) tetralin (0.3 mg/kg). Although
      not quantified in the present study, a concomitant increase in locomotor activity
      was anecdotally observed following R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin.
      These results suggest that systemic administration of a 5-HT1A agonist can reduce
      glutamate neurotransmission in the dopamine-denervated striatum. The results are
      discussed with respect to the treatment of Parkinson's disease.

PMID- 15858410
TI  - Explicit knowledge and intention to learn in sequence learning: an event-related
      potential study.
AB  - The present study was performed to examine how intention to learn and explicit
      knowledge in sequence learning are reflected in event-related potentials.
      Participants responded to numerals presented in a repeating order, which were
      replaced infrequently by deviant numerals. The participants were given incidental
      or intentional learning instructions. Sequence parts for which they acquired
      explicit knowledge were identified for each participant by post-task memory
      tests. Reaction times indicated that sequence learning occurred under both types
      of instruction. The N2 enhancement for deviants was primarily associated with
      explicit sequence knowledge, and the P3 enhancement showed a weak association.
      These results suggested that N2 and P3 reflect different aspects of explicit
      learning.

PMID- 15858411
TI  - Integrin messenger RNAs in the red nucleus after axotomy and neurotrophic
      administration.
AB  - Integrins are cell surface receptors known to be important for regeneration in
      the peripheral nervous system. We have investigated the expression of integrin
      messenger RNAs in red nucleus neurons of adult rats after axotomy and
      administration of neurotrophic factors. Using radioactive in situ hybridization,
      messenger RNA for integrin subunits beta1, alpha3, alpha7 and alphaV could be
      detected. No change of any alpha subunit could be detected after axotomy. In
      contrast, a small upregulation of beta1 was detected after lesion. Administration
      of neurotrophin-3 induced a robust further increase in beta1 messenger RNA
      levels, whereas brain-derived neurotrophic factor did not. By analogy to the
      peripheral nervous system, we propose that integrins may be important for a
      regenerative response in central nervous system neurons.

PMID- 15858412
TI  - Abeta-afferents activate neurokinin-1 receptor in dorsal horn neurons after nerve
      injury.
AB  - We provide new evidence demonstrating that peripheral nerve injury produces
      profound alterations in synaptic input to dorsal horn neurons mediated by non
      nociceptive sensory neurons, and activation of neurokinin-1 receptor may be
      involved in the enhanced synaptic response and thus contribute to the tactile
      allodynia. Our results show that Abeta-fiber-evoked field potential significantly
      increased in the first postoperative week and decreased thereafter while maximal
      mechanical allodynia was exhibited. The neurokinin-1 receptor antagonist L703,606
      significantly reduced Abeta-fiber-evoked field potential in nerve-injured but not
      in sham-operated animals. The non-N-methyl-D-aspartate receptor antagonist CNQX
      inhibited Abeta-fiber-evoked field potential in both nerve-injured and sham
      operated rats, while the N-methyl-D-aspartate receptor antagonist MK-801 did not
      affect Abeta-fiber-evoked field potential in either CCI or sham-operated animals.

PMID- 15858413
TI  - Pattern motion and component motion sensitivity in cat superior colliculus.
AB  - Single neurons in the superior colliculus of the cat were tested for their
      direction-tuning responses to random-line patterns composed of identical short
      lines moving obliquely to their common orientation. A substantial population of
      cells responded primarily to the veridical direction of pattern motion while a
      few were sensitive to the orientation of component lines. Moreover, for most
      cells, the pattern motion sensitivity decreased when the orientation element was
      enhanced by elongating the component lines in stimulus. Further analysis found
      that the initial transient responses after stimulus onset were relatively more
      sensitive to component motion than the subsequent sustained responses. These
      findings suggest that the superior colliculus is involved in the higher-order
      analysis of visual motion so that collicular neurons can signal coherent pattern
      motion in many cases.

PMID- 15858414
TI  - Cloning and expression of a novel isoform of heterogeneous nuclear
      ribonucleoprotein-R.
AB  - In the present study, we cloned a novel isoform of heterogeneous nuclear
      ribonucleoprotein-R (hnRNP-R), hnRNP-R2. Compared with the previously reported
      hnRNP-R (hnRNP-R1), it lacks the exon 5. Two proteins are both nuclear. The
      expression of hnRNP-R1 is not tissue-specific and is strikingly higher than that
      of hnRNR-R2. In comparison, the expression of hnRNP-R2 is low and neural
      specific. The expression of two isoforms is differentially regulated during brain
      development. The results suggest that hnRNP-R may contribute to the regulation of
      neural development through the variation of hnRNP-R components in the hnRNP
      complex.

PMID- 15858415
TI  - Decrease in NF-kappaB, AP-1 and SP-1 activities in neuronal cells expressing
      presenilin 2.
AB  - Decreases in activities of the NF-kappaB, AP-1 and SP-1 transcription factors,
      which could act as antiapoptotic factors, in the presenilin 2 transfected PC12
      cells, either in nontreatment conditions or under apoptotic stimulation, were
      found in this study. Similar results were also found in mice brain cells carrying
      presenilin 2, especially in the mutant gene expressed ones. These findings
      suggested that presenilin 2 may be implicated in neuronal cell death by altering
      the antiapoptotic activity of the transcription factors.

PMID- 15858416
TI  - Spinal cord tissue affects ensheathing cell proliferation and apoptosis.
AB  - This study investigates proliferation and apoptosis of olfactory ensheathing
      cells in cocultures with spinal cord tissue. Proliferation of ensheathing cells
      was significantly increased when cocultured with explants from uninjured spinal
      cord, and spinal cord that had been subjected to chronic contusion or chronic
      needle stab injury, but not to acute needle stab injury. Proliferation rate was
      highest in cocultures with chronically stabbed cord tissue. Contaminating
      (p75NGFR-negative) cells in the cultures showed a significantly higher
      proliferation rate than ensheathing cells. Apoptosis of ensheathing cells was
      significantly increased in cocultures with acutely stabbed spinal cord explants
      compared with chronically contused spinal cord explants. These results suggest
      that delaying transplantation after spinal cord injury may be beneficial to
      ensheathing cell survival.

PMID- 15858417
TI  - Activation of protein kinase C-delta attenuates kainate-induced cell death of
      cortical neurons.
AB  - We investigated the role of individual protein kinase C (PKC) isoforms during
      kainate toxicity in cortical neurons. Treatment with 50 microM kainate induced
      isoform-specific activation of PKC-delta according to the translocation from the
      soluble to the particulate fraction, while it caused remarkable decreases in PKC
      alpha, beta, epsilon and zeta in both fractions. Kainate-induced neuronal death
      was significantly increased by pharmacological inhibition of PKC-delta with
      rottlerin, suggesting a protective role of PKC-delta against kainate toxicity. A
      PKC activator phorbol 12-myristate 13-acetate remarkably attenuated the kainate
      induced neuronal death. Although phorbol 12-myristate 13-acetate activates PKC
      epsilon and PKC-delta, the protective effect of phorbol 12-myristate 13-acetate
      was almost completely abolished by rottlerin, but not by epsilonV1-2. These
      results suggest that activation of PKC-delta attenuates the kainate-induced cell
      death of cortical neurons.

PMID- 15858418
TI  - Actions of orexins on individual myenteric neurons of the guinea-pig ileum:
      orexin A or B?
AB  - The actions of orexins (orexin A and B, 10-300 nM) on individual myenteric
      neurons of the guinea-pig ileum in vitro were compared using intracellular
      recording methods. Both orexins caused membrane depolarizations associated with
      an increase in input neuronal resistance in S and AH neurons via a direct action.
      Orexin depolarizations reversed at about -90 mV, indicating they were due to an
      inactivation of K+ channels. Orexins facilitated fast excitatory postsynaptic
      potentials without affecting postsynaptic sensitivity to acetylcholine and
      adenosine 5'-triphosphate, indicating that the peptides may facilitate ganglionic
      transmission by increasing presynaptic release of neurotransmitters. Orexin B was
      sometimes more effective than orexin A and vice versa. It is concluded that
      orexin B increased neuronal activity via mechanisms similar to orexin A in the
      guinea-pig myenteric plexus.

PMID- 15858419
TI  - Global form perception in cats early deprived of pattern vision.
AB  - Recently, we showed that binocularly deprived cats are not able to detect global
      motion in a random dot pattern (Burnat et al., 2002). Here, we examined, in these
      animals, a global form discrimination task, that is, distinction of a square from
      a rectangle, matched for total surface. In contrast to the previously tested
      motion task, binocularly-deprived cats, as compared with controls, performed only
      at higher thresholds. Interestingly, the increase of the stimuli's surface, or a
      shift from horizontal to vertical orientation of the rectangle, significantly
      impaired their performance. We therefore conclude that binocularly-deprived cats
      do not attend to the global form of the stimuli. Instead, they spontaneously
      choose a local cue to discriminate and are not able to modify it.

PMID- 15858420
TI  - Dissociation of inhibition from error processing using a parametric inhibitory
      task during functional magnetic resonance imaging.
AB  - Inhibition, the process that overrides and reverses the execution of a thought,
      action, or emotion, is important in daily life. Sixteen healthy volunteers
      performed a parametrically modulated motor inhibition task during functional
      magnetic resonance imaging. Two results were observed: (1) increased error
      related anterior cingulate cortex activation and, (2) increased inferior frontal
      gyrus and medial prefrontal cortex activation during inhibition, irrespective of
      errors. Thus, the parametric nature of the task elucidated a functional
      dissociation of brain structures involved in motor inhibition from those involved
      in error processing. Additionally, this task allowed the identification of unique
      areas of increased activation within specific subregions of the anterior
      cingulate cortex related to errors made during trials with a high (dorsal
      anterior cingulate cortex) and low (ventral anterior cingulate cortex) inhibitory
      load.

PMID- 15858421
TI  - Articulation in early and late bilinguals' two languages: evidence from
      functional magnetic resonance imaging.
AB  - The network of cortical and subcortical regions that contribute to articulation
      was examined in bilinguals using functional magnetic resonance imaging.
      Participants were all fluent in French and English: half were bilingual from
      birth and half were 'late bilinguals' who had learned French after the age of 12.
      Overt articulation resulted in the bilateral activation of the motor cortex,
      basal ganglia and cerebellum, and also the supplementary motor area, independent
      of the language spoken. Furthermore, the threshold and extent of the network
      involved in articulation was identical for the two bilingual groups with the
      exception of greater variation in the left putamen for the late bilinguals. These
      data challenge claims that age of acquisition results in fundamental differences
      in the neural substrates that subserve language in bilinguals.

PMID- 15858422
TI  - Event-related potential component associated with the recognition of three
      dimensional objects.
AB  - To understand the physiological process underlying view-invariant object
      recognition, we designed a delayed matching-to-sample task under two different
      conditions: in the first condition, the sample and test stimuli were presented in
      the same view, and in the second, the two stimuli were presented in different
      views. The event-related potential (ERP) component, posterior N1, exhibited a
      significantly larger amplitude when the test image was in the same view as the
      sample image than when the test and the sample images were in different views.
      The result indicates that the posterior N1 is significantly sensitive to view
      association, and clarifies the difference between the neuronal activity that
      occurs in 3D object recognition and 2D image identification at the level of N1.

PMID- 15858423
TI  - Selective utilization of spatial working memory resources during stance posture.
AB  - While it has been shown that visual imagery tasks interfere with balance control,
      the neural mechanisms underlying the interference are unclear. Within a healthy
      young adult population, we employed a dual-task methodology to investigate the
      role of visual working memory in stance postural control. The employment of
      specific visual object and visual spatial working memory cognitive tasks
      facilitated the selective activation of cortically dissociated working memory
      resources. Challenging postural sets did not significantly impact object working
      memory performance, but clearly degraded performance on a spatial working memory
      task, suggesting that interactions between stance postural control and visual
      working memory are limited to the spatial domain. Results demonstrated no
      significant effect of the cognitive tasks upon postural stability.

PMID- 15858424
TI  - Selective and persistent effect of foetal sex on cognition in pregnant women.
AB  - Despite widespread anecdotal complaints of impairment, systematic research
      addressing cognition in gestating women has yielded equivocal results. One way
      that ambiguous findings could arise is if male and female foetuses affect
      maternal cognition in different ways. Using a longitudinal within-participants
      design, we tracked women's cognitive performance from early pregnancy through to
      postnatal resumption of menstruation. On several cognitive tests, the sex of the
      foetus was unrelated to maternal performance. But specifically on difficult tests
      of working memory and spatial ability, a large and enduring effect of foetal sex
      was evident: women pregnant with boys consistently outperformed women pregnant
      with girls. A foetal-derived factor that differs in type or concentration between
      male and female foetuses may thus influence mothers' cognition.

PMID- 15858425
TI  - Mechanisms of orexin A-evoked changes of intracellular calcium in primary
      cultured cortical neurons.
AB  - We have investigated the effect of orexin A on the intracellular free calcium
      concentration ([Ca2+]i) in primary cultured cortical neurons and explored the
      exact mechanisms of orexin A-evoked changes of [Ca2+]i. In the present study,
      changes of [Ca2+]i induced by orexin A in primary cultured cortical neurons were
      first detected by confocal laser scanning microscopy using Ca2+-sensitive dye
      fluo-4 as a novel calcium fluorescent probe. Our results showed that 1-0.1 microM
      orexin A induced the increase in [Ca2+]i in cortical neurons. The increase in
      [Ca2+]i by acute application of orexin A occurred in a dose-dependent manner.
      Orexin A-induced increase in [Ca2+]i was not observed under the condition of Ca2+
      free Dulbecco's modified Eagle's medium. Pretreatment on the cells with 1 microM
      thapsigargin did not block orexin A-evoked response. These findings first
      illuminated the fact that orexin A-induced increase in [Ca2+]i may be mainly from
      extracellular calcium influx in cortical neurons.

PMID- 15858435
TI  - The evolving role of endocrine therapy for early stage breast cancer.

PMID- 15858436
TI  - Development of pharmacogenomic markers to select preoperative chemotherapy for
      breast cancer.
AB  - Individualized selection of the most effective adjuvant (or neoadjuvant)
      chemotherapy for breast cancer based on the molecular characteristics of the
      tumor could improve the risk:benefit ratio of current therapies. It could also
      streamline the development of new regimens for those who are unlikely to benefit
      from existing drugs. It is expected that combinations of markers will be more
      informative to predict response than any single gene and may yield regimen
      specific predictors. Novel molecular analytical tools, particularly
      transcriptional profiling, provide a method to test this hypothesis. Several
      small exploratory studies have shown encouraging results. This article reviews
      recent progress in this field including experience from the breast cancer
      pharmacogenomic marker discovery program at the Nellie B. Connally Breast Center
      of the University of Texas M. D. Anderson Cancer Center. This manuscript is based
      on a presentation that was given during the Presidential Symposium of the annual
      meeting of the Japanese Breast Cancer Society in 2004.

PMID- 15858437
TI  - Translational research in breast cancer.
AB  - Translational research (TR) involves both the development of novel diagnostics
      and novel therapeutics. These two major developmental areas are often associated
      with each other and these associations often bring new paradigms in the
      management of cancer patients. For example, the development of trastuzumab-based
      treatments has been conducted in harmony with the development of new
      methodologies to assess the expression of the Her-2 gene or protein, and from
      this, a therapeutic modality was established for breast cancer patients as a
      novel and individualized treatment system. TR covers a broad spectrum, from
      diagnosis to treatment, and it seems to act as a catalyst for developing novel
      paradigms. Therefore, it is crucial to conduct TR in clinical trials, in
      particular, prospective clinical trials. In this regard, TR can accelerate the
      development of new methodologies and increase trial efficiency. In this review,
      we describe the importance of TR, particularly that related to novel
      therapeutics.

PMID- 15858438
TI  - Treatment outcome of breast-conserving therapy in patients with positive or close
      resection margins: Japanese multi institute survey for radiation dose effect.
AB  - BACKGROUND: The relationship between a positive resection margin and the risk of
      ipsilateral breast tumor recurrence (IBTR) is controversial. To evaluate the
      radiation dose and other factors influencing the ipsilateral breast tumor control
      (IBTC) in patients with positive or close resection margins after breast
      conserving surgery (BCS), the Japanese Radiation Oncology Study Group (JROSG) S
      99-3 study group conducted a multi-institute survey of these patients. METHODS:
      The patients with less than 5 mm tumor-free margins after BCS were eligible for
      this study. A total of 971 patients from 18 institutes were enrolled in the
      analysis. The final pathological margin status was classified into 3 groups.
      Radiation doses to the tumor bed were less than 60 Gy in 252 patients, 60 Gy in
      456 patients and more than 60 Gy in 233 patients. RESULTS: IBTR was observed in
      55 patients (5.8%). The IBTC rates at 5 and 10 years by the Kaplan Meier method
      were 95.6% and 87.3%, respectively. There was no significant difference in 10
      year IBTC rates according to marginal status; 85.9% in positive margin patients,
      91.0% in equal or less than 2 mm margin patients and 87.0% in 2.1-5 mm margin
      patients. Radiation dose to the tumor bed was a marginally significantly
      associated with the 10-year IBTC rate (> or = 60 Gy 90.8% vs < 60 Gy 84.2%, p =
      0.057). In patients with positive margins, IBTC with radiation dose equal to or
      more than 60 Gy was significantly better (p = 0.039). The other factors
      influencing the IBTC were age (> or = 35 years vs < 35 years: p < 0.0001),
      menopausal status (p < 0.0001) and tumor size (p = 0.023). CONCLUSIONS: In
      patients with positive margins, IBTC with radiation dose equal to or more than 60
      Gy was significantly better than the others. We recommend that the tumor bed be
      irradiated with at least 60 Gy in the patients with positive margins. Further
      follow-up is necessary to draw final conclusions.

PMID- 15858439
TI  - Interim analysis of a phase II trial of cyclophosphamide, epirubicin and 5
      fluorouracil (CEF) followed by docetaxel as preoperative chemotherapy for early
      stage breast carcinoma.
AB  - PURPOSE: A single-arm phase II multicenter trial of the combination of
      cyclophosphamide (C), epirubicin (E), and 5-fluorouracil (F) followed by
      docetaxel as neoadjuvant chemotherapy is being conducted by the Japan Breast
      Cancer Research Group. This report describes an interim analysis of the clinical
      response and safety of 79 patients who finished preoperative chemotherapy and
      surgery. PATIENTS AND METHODS: Patients with operable breast cancer received C at
      500 mg/m2, E at 100 mg/m2, and F at 500 mg/m2 every 21 days for 4 cycles followed
      by docetaxel at 75 mg/m2 every 21 days for 4 cycles. RESULTS: Of the 79 patients
      evaluable for analysis the median age was 46 years (28-59), and 61 patients
      (77.2%) had T2 tumors. A total of 312 of 316 (98.7%) cycles of CEF and 296 of 312
      (94.9%) cycles of docetaxel were administered. Average total cumulative dose was
      92% and 95% for CEF and docetaxel, respectively. The rate and grade of edema,
      neuropathy, arthralgia and myalgia were higher with docetaxel than with CEF. The
      overall clinical response rate was 70.9%. Breast conserving surgery was performed
      in 31 of 42 patients (73.8%) with a base-line tumor size of more than 3 cm.
      CONCLUSIONS: Interim data suggest that CEF followed by docetaxel is an active and
      tolerable neoadjuvant chemotherapy regimen. A final analysis is planned for 2005.

PMID- 15858440
TI  - Analysis of ipsilateral breast tumor recurrences after breast-conserving
      treatment based on the classification of true recurrences and new primary tumors.
AB  - BACKGROUND: Ipsilateral breast tumor recurrences (IBTR) after breast-conserving
      treatment include two different entities: true recurrence (TR) thought to occur
      when residual cancer cells grow gradually to detectable size and new primary (NP)
      thought to be de novo cancer independently arising in the preserved breast. The
      patients with ipsilateral breast tumor recurrence (IBTR) are potentially at high
      risk for subsequent distant metastasis, but many studies do not distinguish
      between these types of recurrence. The aim of this study is to clarify the
      biological difference between TR and NP, and to show the clinical significance of
      classifying IBTR into these two types of recurrence. PATIENTS AND METHODS: A
      total of 172 patients with IBTR after breast-conserving therapy from the cohort
      of a long-term large scale study (Research of cancer treatment from the Ministry
      of Health, Labor and Welfare of Japan (no.13-9)) were analyzed. We classified
      IBTRs as TR or NP based on tumor location and pathological findings. The
      characteristics of the primary tumors of TR and NP were compared. Survival rates
      and risk factors of each type of IBTR were examined by the Kaplan-Meier method.
      The results of salvage surgery were also analyzed. RESULTS: Of the 172 patients,
      135 patients were classified as TR and 26 as NP. Eleven cases could not be
      categorized. The primary tumor of TR was characterized by a high rate of lymph
      node metastasis (37.8%) and short disease-free interval (mean DFI; 46.6 months)
      while that of NP showed a rather low lymph node positivity (8.7%) and longer DFI
      (62.1 months). The risk factors for TR were young age, positive surgical margin,
      omission of irradiation and positive lymph node metastasis. Those for NP were
      young age, omission of irradiation and contralateral breast cancer after the
      primary operation. The 5-year survival rates after IBTR were 71.0% in TR and
      94.7% in NP (p=0.022). Salvage operation was performed in 136 IBTRs. Eighty-one
      patients underwent salvage mastectomy and 55 patients underwent repeat
      lumpectomy. Five-year survival rates after salvage operation were 75.7% for
      mastectomy and 84.2% for lumpectomy (N.S.). Twenty percent of patients who
      underwent repeat lumpectomy developed secondary local relapse within 5 years
      after salvage treatment. The risk factors for secondary local relapse were
      analyzed. Limited to cases of IBTR which received radiation therapy after the
      primary operation, NP was the only factor influencing secondary local relapse by
      univariate analysis. CONCLUSIONS: TR and NP show clinically quite different
      features; time to occurrence, characteristics of the original tumor, prognosis
      and risk factor profile for IBTR were all different. Classifying IBTR as TR or NP
      can provide clinically significant data for the management of IBTR.

PMID- 15858442
TI  - Mammary ductoscopy by helical CT: initial experience.
AB  - BACKGROUND: An attempt was made to visualize minute intraductal lesions using
      helical CT in patients with abnormal nipple discharge. METHODS: Galactography was
      performed, immediately followed by CT (ductal CT examination). Based on the image
      data obtained, ductal images were constructed on a workstation using a Pegasus
      viewer (ductal CT imaging). Since no criteria for diagnosis by this method are
      available, ductal CT images were diagnosed by reference to the known ductal
      fiberscopic findings. RESULTS: Ductal CT examination was performed in 10 cases,
      in 9 of whom ductal CT images were successfully constructed. Pathological
      examination was performed in 8 cases. It was possible to observe the structure of
      the luminal surface on the constructed ductoscopic images from all directions,
      but the color tone or the presence or absence of hemorrhage could not be
      observed. CONCLUSIONS: In the examination for abnormal nipple discharge, ductal
      CT examination was useful for intraductal observation. Currently, it is a method
      that allows for observation of the most minute intraductal lesions. However, some
      issues still remain unresolved. The results of this study suggest that further
      studies with more cases hold the promise of making ductal CT imaging a useful
      examination method.

PMID- 15858441
TI  - Classification of ipsilateral breast tumor recurrence after breast-conserving
      therapy: new primary cancer allows a good prognosis.
AB  - PURPOSE: To classify and assess ipsilateral breast tumor recurrences (IBTR) after
      breast-conserving therapy. METHODS: Between 1986 and 2001, 2,137 patients who had
      breast cancer underwent breast-conserving surgery with or without radiotherapy at
      the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. Of
      these patients, 83 (3.9%) had an IBTR. We classified the IBTR as a new primary
      cancer (NP) if the primary tumor had completely negative margins at first
      operation by detailed pathological examination and if the IBTR had an intraductal
      component. All other IBTRs were judged true local recurrence (TR). RESULTS: Of
      the 83 patients, 42 patients were classified as TR (29 had no radiotherapy) and
      41 as NP (40 had no radiotherapy). Mean time to disease recurrence was 37 months
      for TR (52% were within 2 years) versus 55 months for NP (19% were within 2
      years) (p=0.031). Six patients (14%) with TR did not receive re-operation, and
      67% received salvage mastectomy and 19% re-lumpectomy. All cases of NP were
      operable, 78% underwent salvage mastectomy and 22% underwent re-lumpectomy.
      Distant metastases were observed in 33% of patients with TR and 5% of patients
      with NP, and cause-specific death occurred in 6 cases with TR and in one with NP.
      The patients with NP had improved 5-year rates of overall survival (NP 91% vs. TR
      76%, P=0.0627) and distant disease-free survival (NP 93% vs. TR 61%, P=0.0028).
      Patients with NP more often developed contralateral breast cancer (NP 37% vs. TR
      12%, P=0.018) CONCLUSIONS: Patients with NP had better survival rates than those
      with TR. Distinguishing new primary breast carcinomas from local disease
      recurrences may have importance in therapeutic decisions and chemoprevention
      strategies.

PMID- 15858443
TI  - Three-dimensional ultrasound imaging of breast cancer by a real-time
      intraoperative navigation system.
AB  - BACKGROUND: In order to achieve a good cosmetic result without increasing the
      risk of ipsilateral breast cancer recurrence after breast conserving surgery, it
      is very important to minimize the resection volume of the breast without
      compromising the negativity of the surgical margin. For this purpose, it is
      necessary to obtain precise information on tumor extension. We therefore
      developed a three-dimensional (3-D) ultrasound navigation system for breast
      cancer surgery, which can be performed in the operating room just before surgery.
      METHODS: We obtained 3-D breast tumor images by the 3-D ultrasound navigation
      system in 40 patients with primary breast cancer (stage 0-II) who underwent
      mastectomy or breast conserving surgery. The tumor size was measured in a coronal
      view of the 3-D tumor image and compared with the tumor size obtained from a
      pathological map of the tumor extension. RESULTS: We obtained 3-D tumor images in
      38 patients (success rate=95%). The tumor size in the images showed a very strong
      correlation with the pathological tumor size (r=0.898). The difference in tumor
      size between the 3-D images and pathology was less than 1 cm in 29 tumors (76.3%)
      and less than 2 cm in 36 (94.7%). On the other hand, the difference in tumor size
      between palpation and pathology was less than 1 cm in 19 out of 38 tumors (50.0%)
      and less than 2 cm in 29 tumors (76.3%). The absolute difference between the 3-D
      images and pathology was significantly less than that between palpation and
      pathology (p=0.0197). CONCLUSIONS: Our 3-D ultrasound navigation system is useful
      in visualizing breast tumor extension and is more accurate than palpation. The
      system is expected to be helpful in deciding on the appropriate surgical margin
      in breast cancer surgery, resulting in a better cosmetic outcome without
      increasing the risk of surgical margin positivity.

PMID- 15858444
TI  - Statistical estimation of the number of breast cancer patients with disabilities
      resulting from surgery.
AB  - BACKGROUND: The prolongation of the post-operative life of cancer patients brings
      new medical demands. The purpose of this paper is to estimate the total number of
      women patients with breast cancer who will have disability resulting from
      surgical treatment from 2000 to 2020 in Japan. METHODS: The estimation was
      carried out using four indices: the number of cases of women diagnosed with
      breast cancer, the proportion of surgical operations, the frequency of disability
      from surgical treatment, and the crude survival rate of the patient group. The
      crude survival rates of surgically-treated breast cancer patients were estimated
      by the Weibull model. The frequencies of iatrogenic disabilities were calculated
      from several reports of complaints of pain in the chest wall or axilla and
      lymphedema of the arm, and 95% confidence intervals were calculated by the Monte
      Carlo simulation. RESULTS AND DISCUSSION: The number of women patients with
      disability from breast cancer treatment from 2000 to 2020 was estimated to be
      42,016 (95% CI: 41,236, 42,796) people in 2000 and 72,514 (95% CI: 71,196,
      73,832) people in 2020 for pain in the chest wall or axilla, and 22,486 (95% CI:
      22,148, 22,823) people in 2000 and 38,692 (95% CI: 38,094, 39,290) people in 2020
      for lymphedema of the arm. Treatment supports required for the disability are
      medication and social support. Cancer patients with disability after treatment
      need long-term support in their daily life.

PMID- 15858445
TI  - Bilateral breast-conserving therapy for bilateral breast cancer: results and
      consideration of radiation technique.
AB  - BACKGROUND: Although breast-conserving surgery followed by definitive irradiation
      is an established treatment for patients with early breast cancer, the role of
      breast-conserving therapy (BCT) for patients with bilateral breast cancer has not
      been well studied and the radiation therapy technique is still under
      investigation. We examined the feasibility of breast-conserving therapy for
      bilateral breast cancer and present here our radiation therapy technique with CT
      simulator. METHODS: Between July 1990 and December 1998, we treated 17 patients
      with bilateral breast cancer who underwent bilateral breast-conserving surgery
      followed by definitive irradiation. Seven patients had synchronous bilateral
      breast cancer and ten had metachronous bilateral breast cancer. Radiation therapy
      consisted of 50 Gy to the bilateral whole breast in all patients but one. A CT
      simulator was used to plan a tangential radiation field to the breast in all
      patients. Boost irradiation of 10 Gy was administered to 8 tumors with close or
      positive margins. RESULTS: With a median follow-up periods of 95 months from each
      operation, no patients showed loco-regional recurrence on either side, and none
      suffered distant metastasis. Furthermore no serious late adverse effects were
      observed. CONCLUSION: This study demonstrated that BCT is feasible for bilateral
      breast cancer and the CT simulator is useful for determining the radiation field,
      especially when lesions are metachronous.

PMID- 15858446
TI  - Spontaneous " healing" of breast cancer.
AB  - BACKGROUND: Healing is a phenomenon by which the intraductal component of breast
      cancer disappears and is replaced by fibrous tissue. Focally localized healing
      often prevents confirmation of the continuity of intraductal carcinoma.
      OBJECTIVE: To clarify the clinicopathological characteristics of breast cancer
      with healing. PATIENTS AND METHODS: At our hospital, 308 patients (311 breasts)
      underwent breast conservation therapy without neoadjuvant chemotherapy for breast
      cancer in 2000. These surgical specimens were histopathologically investigated
      with 5 mm serial sections. We assessed the proportion and the characteristics of
      breast cancer with healing. RESULTS: (1) The proportion of breast cancer with
      healing was 7% (21/311). (2) In the 21 patients, the mean age was 59.2 years, and
      the mean diameter was 2.8 cm. (3) The histological type of the breast cancer
      varied: noninvasive ductal carcinoma in 2 cases, papillotubular carcinoma in 5,
      solid-tubular carcinoma in 8, scirrhous carcinoma in 5, invasive lobular
      carcinoma in 1, and Paget's disease in 1. However in all cases, the histologic
      type of the intraductal carcinoma foci was the comedo/solid type and the nuclear
      grade of cancer cells was high. (4) In cases with healing, areas of healing were
      seen in an average of 5 (1-26) blocks, compared with intraductal carcinoma foci
      in 13 blocks (2-40). Healing was located on the nipple side of the main lesion in
      8 cases, the peripheral side in 9, and both sides in 4. In 3 cases, healing was
      seen at the surgical margin of the partial mastectomy specimen. CONCLUSION: The
      proportion of breast cancer cases with healing was 7% and these cases were
      intraductal carcinoma of the comedo/solid type, consisting of highly malignant
      cancer cells.

PMID- 15858447
TI  - Invasive cribriform carcinoma with extensive microcalcifications in the male
      breast.
AB  - Invasive cribriform carcinoma (ICC) is a rare, unique type of invasive breast
      carcinoma that exhibits a cribriform pattern in the majority of the invasive
      component and is associated with an excellent prognosis. Only one male patient
      with ICC has been previously reported. Mammography studies often suggest that ICC
      contains microcalcifications, but the histological finding of extensive
      microcalcification has only been reported in one patient with ICC. Here we report
      a male patient diagnosed with ICC and exhibiting histologically confirmed
      extensive microcalcification is reported. The patient was a 64-year-old Japanese
      man in whom a breast tumor was detected during an annual check up. Mammography
      demonstrated a circumscribed high-density mass with microcalcifications. Breast
      conserving surgery with axillary node dissection was performed. The tumor was
      located in the subareolar region of his left breast. The excised tumor had a
      maximum diameter of 1.0 cm, and no signs of invasion to extramammary tissue were
      observed. Histologically, the tumor cells were arranged in a cribriform pattern
      with invasive and non-invasive components. High-grade carcinoma or tubular
      carcinoma components were not observed. Extensive calcification was seen within
      the cribriform spaces. Immunohistological staining revealed that the cribriform
      spaces did not contain basement membrane material, and the tumor cells had not
      differentiated into basaloid cells or lactational mammary epithelium. The patient
      is presently free from local recurrence or metastasis 7 months after undergoing
      surgery.

PMID- 15858448
TI  - A case of carcinosarcoma of the breast.
AB  - Carcinosarcoma is a rare malignant tumor of the breast. A 59-year-old woman was
      admitted to our hospital with a complaint of a right breast mass for one month.
      The mass grew rapidly, and modified radical mastectomy was performed. Based on
      the histological findings of carcinomatous and sarcomatous components entangled
      without a transition area, and the results of immunohistochemical staining,
      carcinosarcoma of the breast was diagnosed. Within 9 months of the surgery, a
      recurrent lesion appeared in her chest wall. As shown by local resection, this
      recurrent tumor had only a carcinomatous component. Such tumors are very rare,
      and there have been no detailed reports of recurrence patterns of carcinosarcoma.
      Here we report our pathological findings in detail.

PMID- 15858449
TI  - Primary non-Hodgkin's lymphoma of the breast: report of a case with special
      reference to 380 cases in the Japanese literature.
AB  - A 52-year-old Japanese woman presented with a mass in the left breast. A tumor
      2.9 cm in diameter was found in the D area on ultrasonography. An ipsilateral
      swollen axillary lymph node was detected. Invasion of the tumor to the pectoralis
      major muscle was seen. Based on a diagnosis of malignant lymphoma by fine needle
      aspiration cytology, radical mastectomy with ipsilateral axillary lymph node
      dissection was performed. Malignant diffuse large B-cell type lymphoma was
      diagnosed histologically according to the World Health Organization
      classification, and the clinical stage was II E by the Ann Arbor staging system.
      Four courses of adjuvant chemotherapy with cyclophosphamide, doxorubicin,
      vincristine and prednisone (CHOP) were subsequently performed. The patient is
      free of recurrence 7 years after surgery. Up to 2002, 380 cases of primary breast
      non-Hodgkin's lymphoma had been documented in the Japanese literature. When the
      tumor size was bigger than 4.5 cm, the outcome was poor. Regarding treatment
      methods, we showed that only enucleation of the tumor is necessary and axillary
      dissection is not necessary. In our case, we thought that the prognosis was good
      despite the large tumor and axillary lymph node metastasis, and that we could
      omit axillary dissection.

PMID- 15858450
TI  - Axons, cells, and depression: the nexus of neurology and psychiatry in multiple
      sclerosis.

PMID- 15858451
TI  - Interactive case conference: Depression in the elderly.

PMID- 15858452
TI  - The paradox of quetiapine in obsessive-compulsive disorder.
AB  - Schizophrenia and obsessive-compulsive disorder (OCD) have historical, clinical,
      and epidemiological links. The clinical use of atypical neuroleptics (ie, dual
      serotonin-dopamine antagonists) to treat both conditions sheds a new light on
      them. We report the first two cases of obsessive-compulsive symptoms (OCS)
      induced by quetiapine in schizophrenia patients. A case of successful
      augmentation by quetiapine in refractory OCD is also presented. A review of the
      literature on OCS induced by atypical neuroleptics follows. This paradoxically
      induced OCD symptomology in schizophrenia patients administered atypical
      neuroleptics is discussed from new pathophysiological and clinical perspectives.
      The discussion emphasizes the prognostic implications of OCS in schizophrenia and
      available therapies for this comorbidity.

PMID- 15858453
TI  - The clinical neuropsychiatry of multiple sclerosis.

PMID- 15858454
TI  - Descriptive epidemiology of affective disorders in multiple sclerosis.
AB  - BACKGROUND: Affective disorders present an important clinical challenge in
      multiple sclerosis (MS). Due to prohibitive sample size requirements, population
      based studies have not yet provided an adequate description of the underlying
      epidemiology of this association. OBJECTIVE: To describe the epidemiology of
      affective disorders in MS in a general population sample. METHODS: The study
      presented here accessed administrative data from a universal healthcare insurance
      plan in the Canadian province of Alberta. Physician billing data recorded in the
      Alberta Health Care Insurance Plan was used to identify members of the population
      >15 years of age with and without MS. Crude and stratified estimates of the
      association between affective disorders and MS were made. Logistic regression
      analysis was used to evaluate statistical interactions and to provide adjusted
      estimates of the association. RESULTS: The estimated prevalence of MS in the
      population within the targeted age range (2.3 million individuals) was
      386/100,000 and that of affective disorders was 7.7%. As expected, an association
      between MS and affective disorders was identified (crude relative prevalence:
      2.2). The association varied in strength over age-sex categories. Although the
      prevalence of affective disorder was higher in women with MS than men with MS,
      the association of MS with affective disorders was stronger in men. The strength
      of association declined with age in both men and women. Affective disorder
      prevalence in people with MS becomes similar to that of the general population in
      older age groups. CONCLUSION: Affective disorders occur with an increased
      frequency in MS. This is true in men and women and across all relevant age
      groups, although the association gets weaker with advancing age. Higher
      frequencies of affective disorder occur in women with MS than in men with MS. The
      frequency of affective disorder in people with MS is highest in the 25-44 age
      group, and declines in older age categories.

PMID- 15858455
TI  - Longitudinal consistency of the relationship between depression symptoms and
      cognitive functioning in multiple sclerosis.
AB  - BACKGROUND: Lifetime prevalence rates of cognitive dysfunction and depression in
      multiple sclerosis (MS) have typically been reported to be approximately 50
      percent. However, an inconsistent relationship between these two common features
      of MS has been reported in the literature. Because neurovegetative depression
      symptoms overlap with MS symptoms, it may be that literature inconsistencies can
      partly be explained by the fact that only those depression symptom clusters
      unambiguously reflective of depression are associated with cognitive dysfunction.
      OBJECTIVE: To explore the relationship between different depression symptom
      clusters and a battery of tests measuring cognitive domains commonly impaired in
      MS and was examined at two time points 3 years apart. METHODS: The Chicago
      Multiscale Depression Inventory was employed to measure mood, negative
      evaluative, and neurovegetative symptom clusters in 53 MS patients who were also
      administered a battery of neuropsychological tests. RESULTS: At time point 1,
      Mood and Evaluative Chicago Multiscale Depression Inventory scales were
      significantly associated with tasks of complex speeded attention, planning, and
      working memory. At time point 2, the Evaluative scale was still significantly
      associated with these domains, in addition to spatial memory; however, all of the
      significant correlations with the Mood scale dropped out. CONCLUSION: These
      results show that negative evaluative depression symptoms are most consistently
      predictive of cognitive dysfunction in MS. It may be that negative evaluative
      depression symptoms use up available cognitive capacity, thus compromising
      performance on cognitive capacity demanding tasks in MS patients.

PMID- 15858456
TI  - Integrating cognitive function screening and assessment into the routine care of
      multiple sclerosis patients.
AB  - Cognitive dysfunction, a common feature of multiple sclerosis (MS), frequently
      leads to impaired activities of daily living, social skills deficits, diminished
      social support, and unemployment. There is growing evidence indicating that
      cognitive impairment is amenable to the effects of medication and behavioral
      counseling. Unfortunately, routine neuropsychological testing is rare in MS
      clinics because screening is ineffective and testing strategies are often too
      cumbersome or expensive. Recent research supports the reliability of a brief
      screening test called the Multiple Sclerosis Neuropsychological Screening
      Questionnaire as well as a minimal neuropsychological battery called the Minimal
      Assessment of Cognitive Function in Multiple Sclerosis. Data indicate that the
      Multiple Sclerosis Neuropsychological Screening Questionnaire has excellent split
      half and test-retest reliability, and that it predicts neuropsychological
      deficiency with good sensitivity and specificity. Recently acquired data also
      show that the Minimal Assessment of Cognitive Function in Multiple Sclerosis
      tests have good test-retest reliability, discriminate MS patients from normal
      controls, and predict unemployment in MS patients. Thus, these or similar methods
      should be employed for the routine monitoring of cognitive functioning of MS
      patients.

PMID- 15858457
TI  - Detecting cognitive dysfunction in multiple sclerosis with a magnetic resonance
      imaging rating scale: a pilot study.
AB  - OBJECTIVE: In multiple sclerosis (MS), magnetic resonance imaging (MRI)
      predictors of cognitive impairment are based on sophisticated computer-generated
      analyses that are difficult to apply in clinical settings. This study
      investigated the clinical usefulness of a new visual rating scale, the
      Cholinergic Pathways Hyperintensities Scale (CHIPS), in detecting cognitive
      dysfunction. METHODS: Forty clinically definite MS patients underwent a brain
      MRI. Based on the CHIPS, cholinergic pathway hyperintensities were rated in 10
      regions on four axial slices. Computerized hyperintense lesion volumes were also
      obtained. For cognitive testing, The Neuropsychological Screening Battery for
      Multiple Sclerosis was used. "Low" and "High" lesion score groups were computed
      based on the mean of the total CHIPS score. Optimal sensitivity and specificity
      of the total CHIPS score in detecting cognitive impairment were determined using
      a receiver operator characteristic curve. RESULTS: Despite a similar demographic
      profile, subjects with a "High" lesion score performed significantly worse than
      the "Low" lesion score group on verbal (P = .007) and visuospatial (P = .02)
      memory, and on a global index of cognitive functioning (P = .001). Optimal
      sensitivity (82%) and specificity (83%) were reached with a threshold total CHIPS
      score of 18 points. Total CHIPS score and total hyperintense lesion load were
      correlated (sigma = 0.82, P < .0001). CONCLUSION: CHIPS is helpful in clinically
      predicting cognitive impairment in MS.

PMID- 15858458
TI  - Can telepsychiatry replace in-person psychiatric assessments? A review and meta
      analysis of comparison studies.
AB  - OBJECTIVE: The authors conducted a review and meta-analysis of the literature
      comparing telepsychiatry with "in-person" psychiatric assessments. METHOD:
      Approximately 380 studies on telepsychiatry published between 1956 and 2002 were
      identified using MEDLINE, PsycINFO, and cross-referenced bibliographies. Of
      these, 14 studies with an N > 10 compared telepsychiatry with in-person
      psychiatry (I-P) using objective assessment instruments or satisfaction
      instruments. Three of these studies compared high bandwidth (HB) with low
      bandwidth (LB) telepsychiatry. RESULTS: Fourteen studies of 500 patients met
      inclusion criteria and were included in the meta-analysis. Telepsychiatry was
      found to be similar to I-P for the studies using objective assessments. Effect
      sizes were on average quite small, suggesting no difference between
      telepsychiatry and I-P. Bandwidth was found to be a significant moderator. Three
      moderators were tested, effect sizes remained largely heterogeneous, and further
      analyses are needed to determine the direction of effect. There was no difference
      between I-P and telepsychiatry between the HB and LB groups, although there are
      anecdotal data suggesting that HB was slightly superior for assessments requiring
      detailed observation of subjects. CONCLUSION: Out of a large telepsychiatry
      literature published over the past 40+ years, only a handful of studies have
      attempted to compare telepsychiatry with I-P directly using standardized
      assessment instruments that permit meaningful comparisons. However, in those
      studies, the current meta-analysis concludes there is no difference in accuracy
      or satisfaction between the two modalities. Over the next few years, we expect
      telepsychiatry to replace I-P in certain research and clinical situations.

PMID- 15858459
TI  - Silicosis mortality, prevention, and control--United States, 1968-2002.
AB  - Silicosis is a preventable occupational lung disease caused by inhaling dust
      containing crystalline silica; no effective treatment for silicosis is available.
      Deaths from inhalation of silica-containing dust can occur after a few months'
      exposure (1). Crystalline silica exposure and silicosis have been associated with
      work in mining, quarrying, tunneling, sandblasting, masonry, foundry work, glass
      manufacture, ceramic and pottery production, cement and concrete production, and
      work with certain materials in dental laboratories. To describe patterns of
      silicosis mortality in the United States, CDC analyzed data from the National
      Institute for Occupational Safety and Health (NIOSH) National Occupational
      Respiratory Mortality System (NORMS) for 1968-2002. This report summarizes the
      results of that analysis, which indicated a decline in silicosis mortality during
      1968-2002 and suggested that progress has been made in reducing the incidence of
      silicosis in the United States. However, silicosis deaths and new cases still
      occur, even in young workers. Because no effective treatment for silicosis is
      available, effective control of exposure to crystalline silica in the workplace
      is crucial.

PMID- 15858460
TI  - Update: hydrogen cyanamide-related illnesses--Italy, 2002-2004.
AB  - Hydrogen cyanamide is used in agriculture as a plant growth regulator and is
      applied to many deciduous plants to stimulate uniform budbreak after dormancy,
      resulting in uniform flowering and maturity. Hydrogen cyanamide is highly toxic,
      and adverse health effects from contact include severe irritation and ulceration
      of the eyes, skin, and respiratory tract. The substance also inhibits aldehyde
      dehydrogenase and can produce acetaldehyde syndrome (e.g., vomiting,
      parasympathetic hyperactivity, dyspnea, hypotension, and confusion) when exposure
      coincides with alcohol use. After Dormex (Degussa AG, Trostberg, Germany), a
      pesticide product containing hydrogen cyanamide (49% by weight), was introduced
      in Italy in 2000, a total of 23 cases of acute illness associated with exposure
      to this chemical were identified in early 2001. This led to a temporary
      suspension of sales and usage of Dormex on February 23, 2002, and strengthening
      of protective measures, as specified on the pesticide label when sales were
      resumed on June 20, 2003. This report describes 28 additional cases of hydrogen
      cyanamide-related illness that occurred during 2002-2004, 14 of which occurred
      after sales resumed. These illnesses suggest that the preventive measures adopted
      in Italy in 2003 to protect workers using hydrogen cyanamide are inadequate.
      Workers exposed to hydrogen cyanamide should be provided adequate information,
      training, personal protective equipment (PPE), and engineering controls.

PMID- 15858461
TI  - Progress toward interruption of wild poliovirus transmission--worldwide, January
      2004-March 2005.
AB  - In 1988, the World Health Assembly of the World Health Organization (WHO)
      resolved to eradicate poliomyelitis globally. Since then, substantial worldwide
      progress has been made toward that goal; the number of countries where polio is
      endemic declined from 125 in 1988 to six by the end of 2003. Further progress in
      2004 toward interruption of transmission has continued in the three Asian
      countries where polio is endemic (Afghanistan, India, and Pakistan). However, in
      2003, two countries in Africa experienced a resurgence of polio cases; the
      resurgence continued to spread in 2004 from the Nigeria-Niger endemic reservoir
      to involve a total of 14 countries that had not reported polio > or =1 year.
      Local transmission of wild poliovirus (WPV) has been reestablished in six of
      these 14 countries, including Sudan, where a major outbreak occurred. This report
      describes global efforts to eradicate polio during January 2004-March 2005 and
      outlines remaining challenges to interrupting transmission in countries where
      polio remains endemic or transmission has been reestablished.

PMID- 15858462
TI  - Recalcitrant chronic actinic dermatitis treated with low-dose thalidomide.

PMID- 15858463
TI  - Human endogenous retroviruses and their possible impact on dermatology.

PMID- 15858464
TI  - Confluent and reticulated papillomatosis without papillomatosis.

PMID- 15858465
TI  - Molecular diagnostics in melanoma.
AB  - Molecular pathology is rapidly evolving, featuring continuous technologic
      improvements that offer novel clinical opportunities for the recognition of
      disease predisposition, for identifying sub-clinical disease, for more accurate
      diagnosis, for selecting efficacious and non-toxic therapy, and for monitoring of
      disease outcome. Currently, the identification and prognosis of primary cutaneous
      melanoma is based on histologic factors (tumor depth and ulceration) and clinical
      factors (number of lymph node and/or distant metastases). However, metastasis can
      occur in patients with thin melanomas, and sentinel lymph node biopsy does not
      identify all patients at risk for distant metastasis. New markers exist that
      correlate with melanoma progression, which may aid in melanoma identification,
      prognostication, and detection of minimal residual disease/early recurrence.
      Moreover, not many therapeutic options exist for melanoma as no regimen prolongs
      survival. Emerging data with investigational therapies suggest that certain
      markers might play a crucial role in identifying patients who will respond to
      therapy or show utility in the monitoring the response to therapy. Herein,
      molecular diagnostics that can potentially benefit the individual melanoma
      patient will be discussed.

PMID- 15858466
TI  - Patterns of Internet use and impact on patients with melanoma.
AB  - BACKGROUND: Patients with cancer and their families frequently, and increasingly,
      turn to outside sources for information, particularly the World Wide Web. Our
      objective was to examine the use of the Internet and its impact among patients
      with melanoma. METHODS: A prospective survey was obtained from 1613 consecutive
      patients with cutaneous melanoma seen at our institution between August 2001 and
      February 2003. Main outcome measures included the ability to access the Internet,
      Internet use to search for melanoma information, and responses to such Internet
      searches. Further analysis of whether there were differences based on age, sex,
      or disease severity was performed. RESULTS: Of patients with melanoma, 39%
      indicated that they had used the Internet to research their disease, 30%
      themselves and 9% had someone else do it for them. Nearly half (47%) of patients
      younger than 40 years researched melanoma on the Internet compared with only 12%
      of patients 60 years or older. Neither sex nor disease severity impacted Internet
      use. The vast majority of patients (94%) thought the Internet was useful, 67%
      believed it helped them better understand their condition, and 45% said they
      would recommend using the Internet to others to find information about medical
      conditions. Roughly a third thought it decreased their anxiety, whereas a similar
      proportion believed the Internet made them more anxious. Increased anxiety
      correlated with decreasing age and increasing disease severity. CONCLUSIONS: The
      use of the Internet is common among patients with melanoma. Anxiety attributed to
      online information about their disease suggests that clinicians caring for
      patients with melanoma should familiarize themselves with online melanoma
      information, and be proactive in assisting their patients in using this resource.

PMID- 15858467
TI  - Site-specific protective effect of broad-spectrum sunscreen on nevus development
      among white schoolchildren in a randomized trial.
AB  - BACKGROUND: Melanocytic nevus density is a strong risk factor for cutaneous
      malignant melanoma. Reducing the number of nevi in children may reduce the risk
      of their developing melanoma as adults. OBJECTIVE: We sought to assess the effect
      of sunscreen use on nevus development by anatomic sites and by nevi of different
      sizes for white schoolchildren in a randomized trial. METHODS: We compared the
      new nevus count between the sunscreen intervention group (n = 145) and the
      control group (n = 164) by anatomic site. RESULTS: Children randomized to the
      sunscreen group had significantly fewer new nevi on the trunk than children in
      the control group. The differences were more pronounced among the freckled
      children than children with no freckles. LIMITATIONS: Potential limitations to
      this study include relatively small numbers of enrolled children, and a follow-up
      period of only 3 years. CONCLUSION: Sunscreen use attenuated new nevus
      development on intermittently sun-exposed body sites for white schoolchildren,
      particularly among the freckled children.

PMID- 15858468
TI  - Large or multiple congenital melanocytic nevi: occurrence of cutaneous melanoma
      in 1008 persons.
AB  - BACKGROUND: There is a dearth of information regarding the occurrence of
      cutaneous melanoma in a large cohort of persons with large congenital melanocytic
      nevi (LCMN) or multiple congenital melanocytic nevi (MCMN). OBJECTIVE: The
      purpose of this article is to report our experience with 1008 persons having LCMN
      and MCMN. METHODS: Information was evaluated that was obtained from a database of
      persons with LCMN or MCMN voluntarily submitted by the affected persons to a
      nevus support group, the Nevus Network. RESULTS: Of those with garment LCMN, 2.9%
      developed cutaneous melanoma associated with 0.8% deaths. Of those with LCMN on
      the head or extremity, 0.3% developed cutaneous melanoma associated with no
      deaths to date. Of the small number with MCMN without a giant nevus, 6.7%
      developed cutaneous melanoma. LIMITATIONS: Attending physician confirmation of
      submitted information was unavailable. Conclusions LCMN and MCMN were associated
      with a low occurrence of cutaneous melanoma in our group.

PMID- 15858469
TI  - Microstaging accuracy after subtotal incisional biopsy of cutaneous melanoma.
AB  - BACKGROUND: A significant portion of cutaneous melanoma may remain after subtotal
      incisional biopsy. The accuracy of microstaging and impact on clinical practice
      in this scenario are unknown. OBJECTIVE: Our purpose was to examine microstaging
      accuracy of an initial incisional biopsy with a significant portion of the
      clinical lesion remaining (> or =50%). METHODS: Patients with cutaneous melanoma,
      diagnosed by incisional biopsy with > or =50% of the lesion remaining, were
      prospectively evaluated for microstaging accuracy, comparing initial Breslow
      depth (BD1) to final depth (BD2) after excision of the residual lesion. Impact on
      prognosis and treatment was also evaluated. RESULTS: Two hundred fifty of 1783
      patients (14%) presented with > or =50% residual clinical lesion after incisional
      biopsy. The mean BD1 was 0.66 mm; the mean BD2, 1.07 mm (P = .001). After
      complete excision of the residual lesion, upstaging occurred in 21% and 10%
      became candidates for sentinel node biopsy. CONCLUSION: An incisional biopsy with
      > or =50% clinical lesion remaining afterward may be inadequate for accurate
      microstaging of melanoma. This scenario is relatively uncommon but clinically
      significant.

PMID- 15858470
TI  - Intratumoral DNA stem-line heterogeneity in superficial spreading melanoma.
AB  - BACKGROUND: In primary melanomas, data on the degree of intratumoral
      heterogeneity to date have been lacking. OBJECTIVE: Our purpose was to
      investigate intratumoral DNA stem-line heterogeneity in superficial spreading
      melanoma (SSM). METHODS: Multiple measuring fields of 54 SSMs (tumor thickness
      median 1.60 mm) were studied by DNA image cytometry to obtain data on the number
      of DNA stem lines per tumor, their ploidy characteristics, and intratumoral
      distribution. Results were compared with standard histopathological criteria.
      RESULTS: Twenty-three of 54 SSMs were found to have two or three distinct
      proliferating tumor cell stem lines (1.46 +/- 0.57 per tumor). Stem lines
      appeared spatially separated in 22 of 23 SMMs. At least 3 measuring fields per
      tumor were necessary to identify all stem lines with a likelihood of 95%. DNA
      heterogeneity correlated with tumor thickness, but occurred in 5 of 19 cases of
      pT1 melanoma. CONCLUSIONS: Primary SSMs can be regarded as potentially clonally
      unstable with a tendency for spatial separation of tumor cell stem lines.

PMID- 15858471
TI  - Tacrolimus ointment is more effective than pimecrolimus cream with a similar
      safety profile in the treatment of atopic dermatitis: results from 3 randomized,
      comparative studies.
AB  - OBJECTIVE: To compare the efficacy and safety of tacrolimus ointment and
      pimecrolimus cream in adult and pediatric patients with mild to very severe
      atopic dermatitis (AD). METHODS: One thousand and sixty-five patients were
      randomized to treatment in 3 multicenter, randomized, investigator-blinded, 6
      week studies. RESULTS: Based on the Eczema Area Severity Index (EASI), tacrolimus
      ointment was more effective than pimecrolimus cream at the end of the study in
      adults (54.1% vs. 34.9%, respectively; P < .0001), in children with
      moderate/severe disease (67.2% vs. 56.4%, respectively; P = .04), in the combined
      analysis (52.8% vs. 39.1%, respectively; P < .0001), and at week 1 in children
      with mild disease (39.2% vs. 31.2%, respectively; P = .04). Tacrolimus was also
      more effective than pimecrolimus based on the Investigator Global AD Assessment
      (IGADA), improvement in percentage of total body surface area affected, and
      improvement in itch scores (P < or = .05), with a faster onset of action. There
      was no significant difference in the incidence of adverse events (AEs), including
      application site reactions in the 2 studies involving 650 children. Adults
      treated with tacrolimus experienced a greater number of local application site
      reactions on day 1; both groups reported a similar incidence of application site
      reactions thereafter. More pimecrolimus-treated patients than tacrolimus-treated
      patients withdrew from the studies because of a lack of efficacy (P < or = .03)
      or adverse events (P = .002; pediatric mild). CONCLUSION: Tacrolimus ointment is
      more effective and has a faster onset of action than pimecrolimus cream in adults
      and children with AD; their safety profiles are similar.

PMID- 15858472
TI  - A retrospective biopsy study of the clinical diagnostic accuracy of common skin
      diseases by different specialties compared with dermatology.
AB  - BACKGROUND: With the recent trend for nondermatologists to treat dermatologic
      disorders, this retrospective biopsy study reviews the accuracy of the clinical
      diagnosis of physicians of different specialties performing surgical dermatologic
      procedures. OBJECTIVE: We assessed the diagnostic abilities of nondermatologist
      physicians who performed various types of skin biopsies and compared them with
      those of dermatologists. METHODS: The clinical diagnoses of family physicians,
      plastic, general, and orthopedic surgeons, and internists and pediatricians
      versus dermatologists were correlated with the histopathologic diagnoses. In
      total, 4451 cases were analyzed. RESULTS: Dermatologists diagnosed twice the
      number of neoplastic and cystic skin lesions correctly (75%) than
      nondermatologists (40%). The clinical diagnosis rendered by family practitioners
      matched the histopathologic diagnosis in only 26% of neoplastic and cystic skin
      lesions. Plastic surgeons, who performed the largest number of cutaneous surgical
      procedures among the nondermatologists, did better in the recognition of skin
      tumors than family physicians, but still had a diagnostic accuracy rate of only
      45%. Inflammatory skin diseases were correctly diagnosed in 71% of the cases by
      dermatologists but in only 34% of the cases by nondermatologists. LIMITATIONS: A
      limitation of this retrospective, unblinded study is the use of the clinical data
      from the pathology requisition form as a surrogate for clinical diagnostic
      accuracy. CONCLUSIONS: The overall accuracy of the clinical diagnosis depends
      heavily on the clinicopathologic correlation. Without sufficient clinical data,
      the histopathologic diagnosis will be limited or restricted. This review
      concludes that without basic dermatology knowledge, clinicopathologic correlation
      is compromised.

PMID- 15858473
TI  - Tefillin dermatitis.
AB  - Tefillin (phylacteries) are a religious article worn by observant Jewish men.
      Only two cases of allergic contact dermatitis from tefillin have been reported
      previously. We describe 7 new cases of tefillin contact dermatitis and review the
      literature on contact allergy caused by religious objects and practices. All our
      patients had contact allergy to potassium dichromate, which was the only allergen
      relevant to tefillin .

PMID- 15858474
TI  - Evolution of skin lesions in Proteus syndrome.
AB  - BACKGROUND: Proteus syndrome is a rare overgrowth disorder that is generally
      progressive, but the natural history of the skin lesions is not known. OBJECTIVE:
      Our purpose was to document the evolution of 4 common skin lesions in 16 patients
      with Proteus syndrome. RESULTS: Most epidermal nevi and vascular malformations
      were reported to appear in the first month of life and had little tendency for
      expansion or development of additional lesions. Subcutaneous lipomas and
      cerebriform connective tissue nevi were commonly noted in the first year of life,
      but not in the first month. Most patients reported that subcutaneous lipomas and
      cerebriform connective tissue nevi progressively increased in size, and in most
      patients additional lesions developed at new locations. Of the 4 types of skin
      lesions, plantar cerebriform connective tissue nevi were most frequently cited as
      a source of symptoms. CONCLUSION: Skin lesions of Proteus syndrome may not appear
      until later infancy or early childhood, making it difficult to diagnose in young
      children.

PMID- 15858475
TI  - Cutaneous type pemphigus vulgaris: a rare clinical phenotype of pemphigus.
AB  - Pemphigus is an autoimmune blistering disease of the skin, mucous membranes, or
      both. There are two main categories of pemphigus: pemphigus foliaceus (PF) and
      pemphigus vulgaris (PV). PV is further subdivided into mucosal dominant and
      mucocutaneous types, according to the extent of cutaneous lesions. These classes
      of pemphigus have distinct histopathologic and serologic findings, with most
      cases falling into these subtypes. We report 4 cases that clinically showed
      blisters and erosions in the skin only, without mucosal involvement. Histologic
      examination of cutaneous lesions demonstrated suprabasilar acantholysis, a
      typical finding for PV. These patients had predominant anti-desmoglein 1 (Dsg1)
      IgG autoantibodies as well as anti-Dsg3 IgG autoantibodies, as determined by
      enzyme-linked immunosorbent assay. The desmoglein compensation theory posits that
      this rare phenotype can be produced by pathogenically weak anti-Dsg3 IgG in the
      presence of potent anti-Dsg1 IgG autoantibodies. Thus, cutaneous type PV without
      apparent mucosal involvement is observed as a rare clinical and histologic
      expression of pemphigus. This expression can be a transient phenotype that may
      develop from, or evolve into, other subtypes of pemphigus.

PMID- 15858476
TI  - Treatment of primary cutaneous B-cell lymphoma with rituximab.
AB  - BACKGROUND: Rituximab is a genetically engineered antibody directed against the
      CD20 antigen. Intravenous administration of rituximab has been used for the
      treatment of patients with low-, intermediate-, and high-grade B-cell non
      Hodgkin's lymphomas and is a registered treatment modality for this indication.
      Treatment of primary cutaneous B-cell lymphoma (CBCL) with intralesionally or
      systemically administered rituximab has been described only in a few cases.
      OBJECTIVE: Our purpose was to assess the efficacy of rituximab in the treatment
      of CBCL. METHODS: We performed a retrospective study on 9 patients with CBCL who
      were treated with intralesional or systemic administration of rituximab. RESULTS:
      Two patients treated with systemic rituximab achieved complete remission.
      Complete remission could be observed in 6 of 7 patients after 1 to 8 cycles of
      intralesional treatment with rituximab. In one patient one of two lesions showed
      a partial remission after 4 cycles of treatment, whereas the second showed
      complete remission. A local recurrence was observed in one patient after 27
      months of follow-up and in two patients recurrences developed at other body sites
      after 12 and 14 months of follow-up. No severe side effect occurred except for
      slight pain during intralesional injection. CONCLUSION: Rituximab therapy is a
      well-tolerated and effective treatment for primary CBCL. In comparison to
      intravenous administration, intralesional application of the drug allows the use
      of lower dosages. Intralesional therapy with rituximab deserves further
      investigation and comparison to systemic administration of the drug in controlled
      multicenter studies.

PMID- 15858477
TI  - Use of a bioengineered skin equivalent for the management of difficult skin
      defects after pediatric multivisceral transplantation.
AB  - BACKGROUND: Primary wound closure is not always possible after pediatric multi
      visceral transplantation because of oversized donor organs and/or intestinal or
      graft edema. We report our experience evaluating the safety and efficacy of
      Graftskin (Apligraf, Organogenesis, Canton, Mass), a bioengineered bi-layered
      human skin equivalent, for the management of difficult skin abdominal defects
      after multivisceral transplantation in a pediatric population. METHODS: A
      retrospective chart review was performed of pediatric multivisceral
      transplantation patients who were treated with Graftskin. Adverse events, course
      of wound reepithelialization, and time for complete closure were recorded.
      RESULTS: Four patients, 7 to 29 months old, were treated with Graftskin. One
      patient died because of unrelated reasons. Stimulation of the granulation,
      reepithelialization, and rapid reduction of the wound surface and depth occurred
      in the other 3 patients. Complete reepithelialization occurred within 5 months.
      No adverse events were noted. CONCLUSION: Graftskin was a successful treatment
      for difficult abdominal skin defects after liver and multivisceral
      transplantation in children.

PMID- 15858478
TI  - Contiguous lesions in lentigo maligna.
AB  - BACKGROUND: Determining the best biopsy technique for a suspected lentigo maligna
      can be challenging. Because complete excisional biopsy is rarely practical, the
      physician is left to choose an appropriate area to biopsy. Sampling error can
      have devastating consequences, especially if the biopsy demonstrates a pigmented
      lesion that was considered in the clinical differential diagnosis. The presence
      of a solar lentigo, pigmented actinic keratosis, or reticulated seborrheic
      keratosis could mislead the pathologist and clinician to the erroneous conclusion
      that the incisional specimen is representative of the whole, and that no lentigo
      maligna is present. OBJECTIVE: We have often observed the presence of a
      contiguous pigmented lesion adjacent to lentigo maligna. The current study was
      designed to determine how frequently this phenomenon occurs. METHODS: We studied
      Mohs debulking specimens of lentigo maligna, and broad shave biopsy specimens of
      pigmented lesions on heavily sun-damaged areas of the skin proven to be lentigo
      maligna. RESULTS: Contiguous pigmented lesions were present in 48% of the
      specimens. The most common lesion was a benign solar lentigo (30%), followed by
      pigmented actinic keratosis (24%). CONCLUSION: Recognition of this phenomenon may
      prevent misdiagnosis of lentigo maligna related to sampling error.

PMID- 15858479
TI  - Granular parakeratosis: pathologic and clinical correlation of 18 cases of
      granular parakeratosis.
AB  - BACKGROUND: Granular parakeratosis (originally termed axillary granular
      parakeratosis) is an idiopathic, benign, nondisabling cutaneous disease that
      manifests with intertriginous erythematous, brown or red, scaly or keratotic
      papules and plaques. It presents in all age groups and has no established
      clinical associations. OBJECTIVES: We wanted to assess the following: (1) the
      incidence of granular parakeratosis in biopsy specimens; (2) the differential
      diagnosis submitted with specimens requisition of granular parakeratosis; and (3)
      variations in its histopathology. METHODS: Between July 1, 1999 and December 31,
      2003, 363,343 specimens were submitted to The Ackerman Institute of
      Dermatopathology in New York. A computer search was done of these specimen
      records and cases diagnosed with granular parakeratosis were reviewed. A
      thickened stratum corneum with retention of keratohyalin granules was considered
      diagnostic of granular parakeratosis. RESULTS: Eighteen of 363,343 specimens
      (0.005%) were diagnosed with granular parakeratosis. The diagnosis was confirmed
      by re-review of specimens. All lesions were located in the axillae. All patients
      were adults; most were women. In only one instance was the correct clinical
      diagnosis of granular parakeratosis submitted with a biopsy requisition of it.
      Granular parakeratosis is rare, if its incidence among biopsy specimens is
      representative of its true prevalence. The failure to include granular
      parakeratosis on biopsy requisition forms of granular parakeratosis specimens
      indicates that dermatologists are not familiar with it. Variations of the
      histopathology of the 18 cases occurred but did not correlate with the clinical
      impressions included on biopsy requisition forms.

PMID- 15858480
TI  - Sunlight, tanning booths, and vitamin D.

PMID- 15858481
TI  - An update on disorders of the nails.

PMID- 15858482
TI  - Dermatoses of pregnancy update.

PMID- 15858483
TI  - Mandatory registration of clinical trials: a major step forward for evidence
      based medicine.

PMID- 15858484
TI  - Medical pearl: rinse-free instant hand sanitizer for use as dermoscopy fluid.

PMID- 15858485
TI  - Medical pearl: pruritus ani and seborrheic dermatitis.

PMID- 15858486
TI  - Student-parent agreement in self-reported sun behaviors.
AB  - OBJECTIVE: We sought to describe agreement between parent proxy and student self
      reported sun behaviors and sun protective practices in adolescents aged 10 to 14
      years. METHODS: We conducted a cross-sectional pilot study of students (n = 52)
      from two classrooms, grades 6 and 7, at a school system in Framingham, Mass. Data
      were collected using self-administered questionnaires. Students were asked to
      report their sun behaviors and sun protective practices. Proxy measures were
      obtained by asking parents to report sun behaviors and practices of their
      children. Agreement was measured using weighted kappa analysis for ordinal data.
      Mean differences (95% confidence intervals) were calculated. RESULTS: The
      response rate for student/proxy pairs was 96% (n = 50). Agreement between student
      and proxy was good for skin color, sunscreen use, number of sunburns in the past
      summer, and application of sunscreen while in other outdoor places (range kappa =
      0.52-0.73). Lowest agreement was found for questions relating to wearing a shirt,
      wearing a hat, sitting in the shade, and frequency of parental sunscreen
      application to the students' backs (range kappa = 0.08-0.28). Mean differences in
      responses between student and proxy respondents were relatively small ranging
      from -0.39 to +0.25. CONCLUSIONS: The lack of a gold standard in the assessment
      of sun exposure and related sun protective practices limits the ability to
      validate these exposure measures in skin cancer studies. The assessment of sun
      exposure behaviors is especially problematic when relying on a child's ability to
      accurately recall these exposures. Parent proxy measures are often used as
      surrogate measures and for validation purposes. We found low to moderate
      student/proxy agreement in this pilot study suggesting that adolescents can
      effectively recall their recent sun behaviors and protective practices when
      compared with parent proxy measures.

PMID- 15858487
TI  - Bullous Sweet's syndrome in congenital neutropenia: association with
      pegfilgrastim.
AB  - Sweet's syndrome is an acute febrile neutrophilic dermatosis marked by attacks of
      painful, plaque-forming inflammatory papules accompanied by fever, arthralgias,
      peripheral leukocytosis, a diffuse dermal neutrophilic infiltrate, and prompt
      resolution of symptoms and lesions with glucocorticoid therapy. There are many
      reports of drug-induced Sweet's syndrome to various medications including all-
      trans -retinoic acid, carbamazepine, hydralazine, levonorgestrel/ethinyl
      estradiol, minocycline, trimethoprim/sulfamethoxazole, and granulocyte colony
      stimulating factor. We describe the first known case of Sweet's syndrome induced
      by pegfilgrastim, a pegylated form of granulocyte colony-stimulating factor with
      unique pharmacologic properties that may induce Sweet's syndrome in patients with
      no history of neutrophilic dermatoses associated with granulocyte colony
      stimulating factor therapy.

PMID- 15858488
TI  - Annular atrophic lichen planus.
AB  - We describe a new case of annular atrophic lichen planus. Annular atrophic lichen
      planus is a rare variant of lichen planus that is clinically characterized by
      violaceous plaques of annular morphology with central atrophy and histopathologic
      findings of annular and atrophic lichen planus, respectively. There have been 4
      cases of this entity reported previously.

PMID- 15858489
TI  - Rash and pancytopenia as initial manifestations of acute graft-versus-host
      disease after liver transplantation.
AB  - Acute graft-versus-host disease is mainly a complication of allogeneic bone
      marrow transplantation, and rarely seen after transplantation of solid organs. We
      describe a 68-year-old man who developed a maculopapular eruption and fever
      approximately 15 days after orthotopic liver transplantation for cryptogenic
      cirrhosis. At day 19, the patient developed abrupt neutropenia and diarrhea. Skin
      biopsy was performed and the specimen revealed basal cell layer vacuolization,
      necrotic keratinocytes, and satellite cell necrosis. Bone-marrow aspiration
      performed after the patient became pancytopenic revealed aplastic marrow with
      scattered lymphocytes and rare megakaryocytes. A diagnosis of acute graft-versus
      host disease was made and an immunosuppressive drug regimen was initiated.
      Unfortunately, the patient died after support was withdrawn because of total
      ablation of his bone marrow and multiorgan failure. This report describes the
      rare presentation of acute graft-versus-host disease after solid organ
      transplantation, and that skin manifestations may be an early presenting sign.

PMID- 15858490
TI  - Benign lymphangiomatous papules of the skin.
AB  - Benign lymphangiomatous papules of the skin are benign lymphatic proliferations
      that may arise in the skin after operation or radiation therapy. We report a case
      of benign lymphangiomatous papules of the skin that occurred in a patient 4 years
      after undergoing radiation therapy to the chest for adenocarcinoma of the breast.

PMID- 15858491
TI  - "Lesion," "rule out...," and other vagaries of filling out pathology requisition
      forms.

PMID- 15858492
TI  - Bullous rheumatoid neutrophilic dermatosis.

PMID- 15858493
TI  - Side effects of naltrexone observed in frequent tanners: could frequent tanners
      have ultraviolet-induced high opioid levels?

PMID- 15858494
TI  - Pigmentary mosaicism and mosaic Turner syndrome.

PMID- 15858495
TI  - Idiopathic eruptive macular pigmentation associated with pregnancy and Hashimoto
      thyroiditis.

PMID- 15858496
TI  - Multiple pigmented epidermal cysts in a white patient.

PMID- 15858497
TI  - Acquired perforating collagenosis in Hodgkin's disease.

PMID- 15858498
TI  - Linear atrophoderma of Moulin: is it a single disease?

PMID- 15858499
TI  - Arthropods in dermatology: errors in arachnology.

PMID- 15858501
TI  - Texas ultraviolet tanning youth access law.

PMID- 15858502
TI  - Subcutaneous Sweet's syndrome: a variant of acute febrile neutrophilic dermatosis
      that is included in the histopathologic differential diagnosis of neutrophilic
      panniculitis.

PMID- 15858503
TI  - Halo dermatitis followed by the development of vitiligo associated with Sutton's
      nevi.
AB  - Halo dermatitis (Meyerson's nevus) is an inflammatory, sometimes itchy,
      eczematous eruption usually encircling a preexisting melanocytic nevus that can
      be mistaken for malignant melanoma or Sutton's nevus. Unlike the latter, it
      mostly resolves spontaneously within weeks and never causes regression of the
      central lesion. Sutton's nevi, however, are frequently found in otherwise healthy
      individuals and patients suffering from vitiligo or malignant melanoma. The
      simultaneous appearance of Sutton's nevus and halo dermatitis has been reported
      before. However, the causes of both diseases remain unclear. We report a 16-year
      old female who developed vitiligo and Sutton's nevi 6 months after a halo
      dermatitis lesion was excised. The coincidence of these disorders suggests common
      or similar immunological mechanisms induced by pigment cells and/or their
      components.

PMID- 15858504
TI  - Chordoma cutis.
AB  - Chordomas are rare malignant primary bone tumors, which most often occur in the
      sacral area. These tumors uncommonly affect the skin, and may not be recognized
      by dermatologists. We present a case of an adult woman with cutaneous metastasis
      of a primary sacral chordoma.

PMID- 15858505
TI  - Generalized petechial eruption induced by parvovirus B19 infection.
AB  - Parvovirus infection classically causes erythema infectiosum. During the past 2
      decades, other unusual skin eruptions have been noted in association with
      parvovirus infection. Papular purpuric gloves and socks syndrome is one form of
      parvovirus infection described mostly in white, young adult patients. Recently,
      there have been reports of a few patients with acropetechial syndrome consisting
      of a papular purpuric gloves and socks syndrome-like presentation with additional
      involvement of the perioral and chin area, temporally associated with acute
      parvovirus B19 infection. We report a case of a 7-year-old boy with serologic
      evidence of acute parvovirus B19 infection who developed a generalized petechial
      eruption with lesions concentrated on his extremities and face. We also reviewed
      the literature and summarized the various cutaneous presentations of parvovirus
      infection.

PMID- 15858506
TI  - Eumycotic mycetoma caused by Cladophialophora bantiana in a patient with systemic
      lupus erythematosus.
AB  - We present the case of a 31-year-old patient who developed widespread mycetoma
      across her back and shoulders caused by Cladophialophora bantiana 16 years after
      injury to those sites from tornado debris. The patient also had a history of
      systemic lupus erythematosus treated with systemic steroids. Systemic antifungal
      treatment with fluconazole and itraconazole proved ineffective, and surgical
      debridement was required. Nine other culture-confirmed cases of cutaneous
      infection with this organism have been reported worldwide. This type of infection
      can occur in immunocompromised or immunocompetent patients, and may respond to
      systemic antifungals or surgery.

PMID- 15858507
TI  - Acne fulminans with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO)
      syndrome treated with infliximab.
AB  - Acne fulminans is a syndrome of sudden onset hemorrhagic and ulcerative acne
      involving the back, chest, and face combined with systemic symptoms. It can be
      the dermatologic manifestation of the synovitis-acne-pustulosis-hyperostosis
      osteitis (SAPHO) syndrome. Current therapy for acne fulminans consists of wound
      care, topical and systemic corticosteroids, isotretinoin, and nonsteroidal anti
      inflammatory drugs (NSAIDs). Infliximab, a recently developed monoclonal antibody
      against tumor necrosis factor-alfa, has shown efficacy in the treatment of
      psoriatic arthritis and ankylosing spondylitis both of which share clinical
      similarities to the SAPHO syndrome. We report the case of a patient with the
      SAPHO syndrome and acne fulminans who was treated with infliximab. Ten months
      after initiating therapy with infliximab, the area of the patient's ulcerative
      lesions was reduced by 70%. Infliximab might be considered as a treatment option
      for patients with acne fulminans unresponsive to conventional therapies.

PMID- 15858509
TI  - Elevated serum immunoglobulin preceding primary cutaneous posttransplant
      lymphoproliferative disorder.

PMID- 15858508
TI  - High-dose chemotherapy with autologous blood stem cell transplantation for
      aggressive subcutaneous panniculitis-like T-cell lymphoma.

PMID- 15858510
TI  - Primary carcinosarcoma of the skin.

PMID- 15858511
TI  - Ampicillin-induced cutaneous eruption associated with Epstein-Barr virus
      reactivation.

PMID- 15858512
TI  - Cutaneous tuberculosis diagnosis in an inhospitable Amazonian region by means of
      telemedicine and molecular biology.
AB  - We report on a 13-year-old boy who displayed a chronic granulomatous inflammatory
      reaction of 5 years duration. The lesion was resistant to different antibiotic
      schemes; his routine laboratory tests and chest radiographs were normal.
      Teledermatologic consultation and histopathologic study of skin biopsy suggested
      scrofulodermal tuberculosis. Polymerase chain reaction amplification of DNA
      extracted from lymph node biopsy was taken as starting material for dot-blot
      hybridization using Mtp-40 and IS 6110 as probes for detecting either
      Mycobacterium tuberculosis or any mycobacteria belonging to the M tuberculosis
      complex, respectively. Positive results in both hybridizations were further
      confirmed by culturing in BACTEC MGIT 960 system. The lesion greatly diminished
      following isoniazid, rifampin, and ethambutol treatment. Telemedicine allowed a
      cutaneous tuberculosis diagnosis to be made of a patient living in a remote town
      located in the Amazon jungle by using molecular biology techniques.

PMID- 15858513
TI  - Rice nightmare: Kwashiorkor in 2 Philadelphia-area infants fed Rice Dream
      beverage.
AB  - A 14-month-old girl and a 7-month-old boy each presented with a diffuse
      dermatitis, whole body edema, and hypoalbuminemia. The diets of both infants
      consisted almost entirely of Rice Dream, a rice-based, protein-poor beverage.
      Both infants were diagnosed with kwashiorkor, which resolved with protein
      supplementation. Clues from the physical examination, a diet history, appropriate
      laboratory examinations, and an index of suspicion are crucial in promptly
      diagnosing and treating infants with kwashiorkor. Manufacturers of rice beverages
      should appropriately warn parents about the dangers of using their products as
      infant nourishment.

PMID- 15858514
TI  - Primary cutaneous follicular center cell lymphoma of the nose with maxillary
      sinus involvement in a pediatric patient.
AB  - We report a primary cutaneous follicular center cell lymphoma (PCFCCL) that arose
      on the nose and the left naso-labial fold, spread to the left cheek, the left
      maxillary sinus, and the soft palate in a 16-year-old boy. Polychemotherapy was
      performed and the patient is disease-free after 41 months. This case is unusual
      because PCFCCL rarely arises on the nose, only occasionally disseminates to
      extracutaneous sites, and, to our knowledge, has never been described in
      pediatric patients.

PMID- 15858515
TI  - A rare case of fatal primary cutaneous mucinous carcinoma of the scalp with
      multiple in-transit and pulmonary metastases.
AB  - BACKGROUND: Primary cutaneous mucinous carcinoma is a rare neoplasm derived from
      the sweat glands. It is usually located in the head and neck region, with the
      eyelids being the most common site of presentation. Recurrence following primary
      excision is common but metastasis is rare. CASE REPORT: We report a patient
      presenting with rapidly progressive cutaneous mucinous carcinoma on the right
      parietal scalp. Systemic work-up failed to reveal an occult primary source. The
      tumor was treated with Mohs micrographic surgery with clear margins. However,
      within two months, the patient developed new lesions on the scalp both adjacent
      to and separate from the original previously excised area, as well as metastasis
      to the right parotid gland. The patient received adjuvant radiation therapy both
      to the scalp lesions and to the parotid gland with apparent control of
      locoregional disease. However, two weeks after completing radiation therapy, the
      patient was found to have developed pulmonary metastases and died soon
      thereafter. CONCLUSION: Primary mucinous carcinoma arising in the skin is rare
      and usually follows an indolent course. We report the rare occurrence of a
      mucinous carcinoma of the scalp that developed multiple cutaneous tumors caused
      by in-transit metastases, as well as parotid gland metastases and eventual fatal
      pulmonary metastases.

PMID- 15858516
TI  - Photoaging and phototoxicity from long-term voriconazole treatment in a 15-year
      old girl.
AB  - Voriconazole is a second-generation triazole that was approved by the Food and
      Drug Administration in May 2002 for treatment of severe fungal infections. In
      clinical trials it demonstrated superior efficacy in addition to a survival
      benefit when compared with the then current treatment standard, amphotericin B,
      for primary treatment of invasive aspergillosis. Voriconazole is a highly
      selective inhibitor of fungal cytochrome P450 enzymes. Adverse cutaneous
      reactions have been reported, namely cheilitis, erythema, discoid lupus
      erythematosus, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema
      multiforme, and photosensitivity reactions. We report a case of photoaging caused
      by voriconazole therapy. A 15-year-old patient developed cheilitis and erythema
      over the sun-exposed areas of her body 5 weeks after beginning voriconazole for a
      severe fungal infection. The lesions showed a mild transient improvement before
      subsequent photodamage occurred to the back of her forearms, back of her hands,
      and face. Voriconazole was discontinued once the fungal infection had completely
      resolved. The patient's blisters, erythema, and cheilitis resolved after
      discontinuation of voriconazole. However, she was left with solar elastotic
      changes, multiple lentigines, and ephelides of sun-exposed areas. These cutaneous
      manifestations may represent a unique adverse event caused by a new second
      generation triazole.

PMID- 15858517
TI  - Tuberous and tendinous xanthomata secondary to ritonavir-associated
      hyperlipidemia.
AB  - Xanthomas most often occur in conjunction with a primary or secondary disorder of
      lipid metabolism. A range of metabolic disturbances has been described in
      association with protease inhibitors, including lipodystrophy, hyperglycemia, and
      hyperlipidemia. Ritonavir has been repeatedly shown to be the most common
      protease inhibitor to induce these metabolic abnormalities. This report
      highlights a case of both tuberous and tendinous xanthomata secondary to
      ritonavir-associated hyperlipidemia.

PMID- 15858518
TI  - Subepidermal blistering disease with autoantibodies to both the p200 autoantigen
      and the alpha3 chain of laminin 5.
AB  - Anti-p200 pemphigoid and anti-laminin 5 mucous membrane pemphigoid are two
      distinct autoimmune blistering skin diseases. Patients with anti-p200 pemphigoid
      demonstrate circulating autoantibodies to an unknown 200-kd acidic noncollagenous
      glycoprotein of the lower lamina lucida, whereas anti-laminin 5 mucous membrane
      pemphigoid is characterized by an autoimmune response against the major basement
      membrane adhesion molecule laminin 5. In this report, we describe a patient who
      developed a recurrent nonscarring blistering eruption, affecting both skin and
      mucous membranes. Immunoblotting of dermal extracts and extracellular matrix of
      cultured keratinocytes revealed circulating autoantibodies directed to the p200
      antigen and the alpha3 chain of laminin 5, respectively. The unusual clinical and
      immunologic profile of this case suggests that molecular specificity of
      circulating autoantibodies affects the clinical presentation of autoimmune
      subepidermal blistering skin diseases.

PMID- 15858519
TI  - Methotrexate-induced bullous acral erythema in a child.
AB  - Chemotherapy induced acral erythema (CIAE) is an uncommon and dramatic reaction
      to high-dose chemotherapy. It is characterized by symmetrical, well-demarcated,
      painful erythema of the palms and soles which may progress to bullae formation
      and desquamation. Prompt recognition and discrimination from more serious
      conditions such as graft-vs-host disease or toxic epidermal necrolysis is
      essential. This paper describes the case of a 12-year-old boy who developed CIAE
      after high-dose methotrexate treatment and discusses the important clinical,
      histopathological, and therapeutic features of this condition.

PMID- 15858520
TI  - Eruptive nevi of the palms and soles.
AB  - The sudden eruption of atypical and benign melanocytic nevi has been associated
      with a number of disease states and primary skin conditions. Most case reports
      and series of patients have linked eruptive nevi with blistering skin disease or
      immunosuppression. Subsets of patients in the immunosuppressed category have
      remarkably increased numbers of nevi on the palms and soles. We describe a case
      of multiple eruptive nevi of the palms and soles in association with
      immunosuppression, and the potential underlying mechanisms promoting such
      nevogenesis are explored. Although both the absolute number of nevi and presence
      of dysplastic nevi have been correlated with an increased relative risk of
      melanoma, actual risk of melanoma in patients with eruptive nevi is unknown.

PMID- 15858522
TI  - Interdisciplinary education and practice: moving from reformation to
      transformation.

PMID- 15858523
TI  - Critical thinking and patient outcomes: a review.
AB  - There has been a multidisciplinary plethora of critical thinking definitions
      stemming from educators in 1912 1 through and inclusive of today. As nurses'
      roles change in response to the dynamics of managed care and an increase in use
      of biotechnology in health care, more is expected of them both in terms of
      psychomotor and cognitive skills. The American Association for Colleges of
      Nursing requires that critical thinking be reflected within academic nursing
      programs as a core competency for program accreditation. 2 Although critical
      thinking has been associated with and evaluated in regard to learning outcomes,
      little information exists which links critical thinking to patient outcomes. The
      purpose of this article is to provide a literature review of critical thinking
      and to explore a possible link between nurses' critical thinking and patient
      outcomes.

PMID- 15858524
TI  - Health and safety of older nurses.
AB  - The nursing workforce is aging at an unprecedented rate yet little is known about
      the health and safety of older registered nurses (RNs). The survey reported here
      examined the relationships between demographic variables, job attributes (job
      satisfaction, control over practice, and job demands) and the physical and mental
      health and job-related injuries and health disorders of 308 nurses over the age
      of 50. Findings indicate that nurses with higher job satisfaction, higher control
      over practice, and lower job demands experienced increased physical health.
      Increasing age was positively correlated with mental health. Almost a quarter of
      older RNs experienced a job-related injury within the past 5 years, and over a
      third experienced job-related health problems. Nurses with higher job demands and
      those employed in hospital settings were more likely to have an injury. Overall,
      older RNs reported higher levels of physical and mental health than the national
      norm. Efforts must be made to keep older RNs healthy so we can retain them in the
      workforce.

PMID- 15858525
TI  - Participant-centered adaptations in caregiver trials: strategies for managing
      confounds.
AB  - BACKGROUND: Randomized trials have been criticized for being more protocol than
      participant-centered, with concerns raised about higher subject attrition and
      limited generalizability under controlled conditions. Informal caregivers are
      similar to other participants in community-based trials: many are unlikely to
      remain in a trial without procedural adaptations to meet some of their needs.
      PURPOSE: This article discusses design and statistical strategies for tracking
      potential confounds associated with 3 participant-centered adaptations that may
      be made in community-based caregiver trials: tailoring multi-component
      interventions, using interpersonal contacts for participant maintenance, and non
      blinding of trial participants. The intent of the article is to initiate dialogue
      on the seldom-discussed issue of participant-centered adaptations in community
      based trials. CONCLUSIONS: Participant-centered adaptations may reduce subject
      attrition and enhance generalizability, but protocol adaptation can compromise
      trial integrity. The challenge for investigators is to develop scientifically
      sound methods for tracking / controlling potential confounds associated with each
      adaptation.

PMID- 15858526
TI  - Evaluating HIPAA compliance: a guide for researchers, privacy boards, and IRBs.
AB  - The purpose of this article is to describe implications of the Health Information
      Portability and Accountability Act of 1996 (HIPAA) for nurses engaged in human
      and health services research. In general, a person's private health information
      (PHI) may only be disclosed for treatment, payment, and business procedures
      related to healthcare service delivery. Access and/or use of the same information
      for research purposes necessitates another layer of review and may require a
      separate process of authorization. A brief historical overview of regulatory
      requirements regarding health information privacy and security standards for the
      electronic transformation of data and protection of electronically kept medical
      records is discussed and related to the role and responsibilities of researchers
      and organizations where research is conducted. In addition, a generic document
      template adaptable for use by an individual or organization is presented that can
      provide a quick, systematic review of HIPAA compliance when a research proposal
      is being developed or is received that seeks access to PHI.

PMID- 15858527
TI  - Biological researchers: building nursing science.
AB  - Nursing science addresses the individual from a multidimensional perspective, and
      the questions nurses generate from their practice are often grounded in basic
      biology. However, concern is frequently voiced as to whether there is adequate
      preparation and support for biological researchers within nursing. This study
      reports on a survey of nurse investigators funded by the National Institutes of
      Health who carry out biological research. All study participants were current
      faculty, and 48% had post-doctoral training. The majority worked with animal
      models. Research areas ranged from cell and molecular biology to delivery of
      health care. Some participants reported tension between their work and how others
      view "typical" nursing research. All participants had been awarded federal
      research funding, primarily from the National Institute of Nursing Research
      (NINR), and most reported receiving small grants from other funding organizations
      early in their careers. Self-identified factors influencing success included
      mentoring, flexibility, persistence, and hard work.

PMID- 15858528
TI  - Discharge planning, nursing home placement, and the Internet.
AB  - BACKGROUND: Effective discharge planning and well-coordinated case management
      related to nursing home (NH) placement are key services in acute-care hospitals.
      OBJECTIVES: (1) identify the individuals and important factors involved in the
      discharge planning process; (2) describe the types/sources of information used by
      discharge planners to recommend specific nursing homes for patients and families;
      and (3) determine which methods are used to evaluate the quality of US nursing
      homes (NHs). METHODS: Descriptive study, with a convenience sample of 41
      discharge planners and case managers from California acute-care hospitals.
      RESULTS: This study found that patients, families, friends, and physicians are
      all involved in the discharge planning process along with discharge planners
      and/or case managers. Discharge planners/case managers were generally concerned
      about NH bed availability, geographic location, and financial considerations.
      Although the discharge planners and case managers were able to articulate
      important indicators of quality in NHs, such information was not routinely
      considered during discharge planning activities. CONCLUSIONS: Discharge planners
      and case managers need to play a more central role in the decision-making process
      related to the selection of a NH, especially because decisions are time-limited
      and can benefit from a well-planned discharge planning program that uses a
      variety of data on quality and costs. The widespread use of Internet-based
      information sources can be expanded to aid this process.

PMID- 15858529
TI  - The American Nurses Foundation 1955-2005, celebrating 50 years of promoting the
      public health and advancing the nursing profession.

PMID- 15858530
TI  - AAN Member Spotlight: educating for leadership: an outreach approach.

PMID- 15858531
TI  - Functional, perfusion and diffusion MRI of acute focal ischemic brain injury.
AB  - Combined functional, perfusion and diffusion magnetic resonance imaging (MRI)
      with a temporal resolution of 30 mins was performed on permanent and transient
      focal ischemic brain injury in rats during the acute phase. The apparent
      diffusion coefficient (ADC), baseline cerebral blood flow (CBF), and functional
      MRI (fMRI) blood-oxygen-level-dependent (BOLD), CBF, and CMRO(2) responses
      associated with CO(2) challenge and forepaw stimulation were measured. An
      automated cluster analysis of ADC and CBF data was used to track the spatial and
      temporal progression of different tissue types (e.g., normal, 'at risk,' and
      ischemic core) on a pixel-by-pixel basis. With permanent ischemia (n=11), forepaw
      stimulation fMRI response in the primary somatosensory cortices was lost,
      although vascular coupling (CO(2) response) was intact in some animals. Control
      experiments in which the right common carotid artery was ligated without causing
      a stroke (n=8) showed that the delayed transit time had negligible effect on the
      fMRI responses in the primary somatosensory cortices. With temporary (15-mins,
      n=8) ischemia, transient CBF and/or ADC declines were observed after reperfusion.
      However, no T(2) or TTC lesions were observed at 24 h except in two animals,
      which showed very small subcortical lesions. Vascular coupling and forepaw fMRI
      response also remained intact. Finally, comparison of the relative and absolute
      fMRI signal changes suggest caution when interpreting percent changes in disease
      states in which the baseline signals are physiologically altered; quantitative
      CBF fMRI are more appropriate measures. This approach provides valuable
      information regarding ischemic tissue viability, vascular coupling, and
      functional integrity associated with ischemic injury and could have potential
      clinical applications.

PMID- 15858532
TI  - Stargazin modulates AMPA receptor gating and trafficking by distinct domains.
AB  - AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors
      mediate fast excitatory synaptic transmission in the brain. These ion channels
      rapidly deactivate and desensitize, which determine the time course of synaptic
      transmission. Here, we find that the AMPA receptor interacting protein,
      stargazin, not only mediates AMPA receptor trafficking but also shapes synaptic
      responses by slowing channel deactivation and desensitization. The cytoplasmic
      tail of stargazin determines receptor trafficking, whereas the ectodomain
      controls channel properties. Stargazin alters AMPA receptor kinetics by
      increasing the rate of channel opening. Disrupting the interaction of stargazin
      ectodomain with hippocampal AMPA receptors alters the amplitude and shape of
      synaptic responses, establishing a crucial function for stargazin in controlling
      the efficacy of synaptic transmission in the brain.

PMID- 15858533
TI  - Fisheries: decline of Pacific tuna populations exaggerated?

PMID- 15858535
TI  - New accountability in China.

PMID- 15858536
TI  - Dealing with design.

PMID- 15858537
TI  - Turkish government accused of hijacking boosted science budget.

PMID- 15858538
TI  - Satellite tags give fresh angle on tuna quota.

PMID- 15858539
TI  - Physicists look to crystal device for future of fusion.

PMID- 15858540
TI  - Link to infection raises hope of preventing child leukaemia.

PMID- 15858541
TI  - US experts draw up guidelines for stem-cell research.

PMID- 15858542
TI  - Corporate culture nets big bucks for university heads.

PMID- 15858543
TI  - Climate change blamed for rise in hay fever.

PMID- 15858545
TI  - Intelligent design: who has designs on your students' minds?

PMID- 15858546
TI  - Quantum physics: the philosopher of photons.

PMID- 15858548
TI  - DNA barcoding does not compete with taxonomy.

PMID- 15858549
TI  - A drug is effective if better than a harmless control.

PMID- 15858553
TI  - Predicting with unpredictability.

PMID- 15858554
TI  - Astrophysics: a certain flare.

PMID- 15858555
TI  - Evolutionary biology: animal roots and shoots.

PMID- 15858556
TI  - Technology: warm fusion.

PMID- 15858558
TI  - Behavioural ecology: cue for kin.

PMID- 15858559
TI  - HIV: viral blitzkrieg.

PMID- 15858560
TI  - Obituary: Maurice R. Hilleman (1919-2005).

PMID- 15858562
TI  - Nanotechnology: high-speed integrated nanowire circuits.
AB  - Macroelectronic circuits made on substrates of glass or plastic could one day
      make computing devices ubiquitous owing to their light weight, flexibility and
      low cost. But these substrates deform at high temperatures so, until now, only
      semiconductors such as organics and amorphous silicon could be used, leading to
      poor performance. Here we present the use of low-temperature processes to
      integrate high-performance multi-nanowire transistors into logical inverters and
      fast ring oscillators on glass substrates. As well as potentially enabling
      powerful electronics to permeate all aspects of modern life, this advance could
      find application in devices such as low-cost radio-frequency tags and fully
      integrated high-refresh-rate displays.

PMID- 15858563
TI  - Earth science: microseismicity data forecast rupture area.
AB  - On 28 September 2004 there was an earthquake of magnitude 6.0 at Parkfield,
      California. Here we show that the size distribution of the micro-earthquakes
      recorded in the decades before the main shock occurred allowed an accurate
      forecast of its eventual rupture area. Applying this approach to other well
      monitored faults should improve earthquake hazard assessment in future.

PMID- 15858564
TI  - Reduced sleep in Drosophila Shaker mutants.
AB  - Most of us sleep 7-8 h per night, and if we are deprived of sleep our performance
      suffers greatly; however, a few do well with just 3-4 h of sleep-a trait that
      seems to run in families. Determining which genes underlie this phenotype could
      shed light on the mechanisms and functions of sleep. To do so, we performed
      mutagenesis in Drosophila melanogaster, because flies also sleep for many hours
      and, when sleep deprived, show sleep rebound and performance impairments. By
      screening 9,000 mutant lines, we found minisleep (mns), a line that sleeps for
      one-third of the wild-type amount. We show that mns flies perform normally in a
      number of tasks, have preserved sleep homeostasis, but are not impaired by sleep
      deprivation. We then show that mns flies carry a point mutation in a conserved
      domain of the Shaker gene. Moreover, after crossing out genetic modifiers
      accumulated over many generations, other Shaker alleles also become short
      sleepers and fail to complement the mns phenotype. Finally, we show that short
      sleeping Shaker flies have a reduced lifespan. Shaker, which encodes a voltage
      dependent potassium channel controlling membrane repolarization and transmitter
      release, may thus regulate sleep need or efficiency.

PMID- 15858565
TI  - An exceptionally bright flare from SGR 1806-20 and the origins of short-duration
      gamma-ray bursts.
AB  - Soft-gamma-ray repeaters (SGRs) are galactic X-ray stars that emit numerous short
      duration (about 0.1 s) bursts of hard X-rays during sporadic active periods. They
      are thought to be magnetars: strongly magnetized neutron stars with emissions
      powered by the dissipation of magnetic energy. Here we report the detection of a
      long (380 s) giant flare from SGR 1806-20, which was much more luminous than any
      previous transient event observed in our Galaxy. (In the first 0.2 s, the flare
      released as much energy as the Sun radiates in a quarter of a million years.) Its
      power can be explained by a catastrophic instability involving global crust
      failure and magnetic reconnection on a magnetar, with possible large-scale
      untwisting of magnetic field lines outside the star. From a great distance this
      event would appear to be a short-duration, hard-spectrum cosmic gamma-ray burst.
      At least a significant fraction of the mysterious short-duration gamma-ray bursts
      may therefore come from extragalactic magnetars.

PMID- 15858566
TI  - An expanding radio nebula produced by a giant flare from the magnetar SGR 1806
      20.
AB  - Soft gamma-ray repeaters (SGRs) are 'magnetars', a small class of slowly spinning
      neutron stars with extreme surface magnetic fields, B approximately 10(15) gauss
      (refs 1 , 2 -3). On 27 December 2004, a giant flare was detected from the
      magnetar SGR 1806-20 (ref. 2), only the third such event recorded. This burst of
      energy was detected by a variety of instruments and even caused an ionospheric
      disturbance in the Earth's upper atmosphere that was recorded around the globe.
      Here we report the detection of a fading radio afterglow produced by this
      outburst, with a luminosity 500 times larger than the only other detection of a
      similar source. From day 6 to day 19 after the flare from SGR 1806-20, a
      resolved, linearly polarized, radio nebula was seen, expanding at approximately a
      quarter of the speed of light. To create this nebula, at least 4 x 10(43) ergs of
      energy must have been emitted by the giant flare in the form of magnetic fields
      and relativistic particles.

PMID- 15858567
TI  - A giant gamma-ray flare from the magnetar SGR 1806-20.
AB  - Two classes of rotating neutron stars-soft gamma-ray repeaters (SGRs) and
      anomalous X-ray pulsars-are magnetars, whose X-ray emission is powered by a very
      strong magnetic field (B approximately 10(15) G). SGRs occasionally become
      'active', producing many short X-ray bursts. Extremely rarely, an SGR emits a
      giant flare with a total energy about a thousand times higher than in a typical
      burst. Here we report that SGR 1806-20 emitted a giant flare on 27 December 2004.
      The total (isotropic) flare energy is 2 x 10(46) erg, which is about a hundred
      times higher than the other two previously observed giant flares. The energy
      release probably occurred during a catastrophic reconfiguration of the neutron
      star's magnetic field. If the event had occurred at a larger distance, but within
      40 megaparsecs, it would have resembled a short, hard gamma-ray burst, suggesting
      that flares from extragalactic SGRs may form a subclass of such bursts.

PMID- 15858568
TI  - Repeated injections of energy in the first 600 ms of the giant flare of SGR 1806
      20.
AB  - The massive flare of 27 December 2004 from the soft gamma-ray repeater SGR 1806
      20, a possible magnetar, saturated almost all gamma-ray detectors, meaning that
      the profile of the pulse was poorly characterized. An accurate profile is
      essential to determine physically what was happening at the source. Here we
      report the unsaturated gamma-ray profile for the first 600 ms of the flare, with
      a time resolution of 5.48 ms. The peak of the profile (of the order of 10(7)
      photons cm(-2) s(-1)) was reached approximately 50 ms after the onset of the
      flare, and was then followed by a gradual decrease with superposed oscillatory
      modulations possibly representing repeated energy injections with approximately
      60-ms intervals. The implied total energy is comparable to the stored magnetic
      energy in a magnetar (approximately 10(47) erg) based on the dipole magnetic
      field intensity (approximately 10(15) G), suggesting either that the energy
      release mechanism was extremely efficient or that the interior magnetic field is
      much stronger than the external dipole field.

PMID- 15858569
TI  - Detection of a radio counterpart to the 27 December 2004 giant flare from SGR
      1806-20.
AB  - It was established over a decade ago that the remarkable high-energy transients
      known as soft gamma-ray repeaters (SGRs) are located in our Galaxy and originate
      from neutron stars with intense (< or = 10(15)G) magnetic fields-so-called
      'magnetars'. On 27 December 2004, a giant flare with a fluence exceeding 0.3 erg
      cm(-2) was detected from SGR 1806-20. Here we report the detection of a fading
      radio counterpart to this event. We began a monitoring programme from 0.2 to 250
      GHz and obtained a high-resolution 21-cm radio spectrum that traces the
      intervening interstellar neutral hydrogen clouds. Analysis of the spectrum yields
      the first direct distance measurement of SGR 1806-20: the source is located at a
      distance greater than 6.4 kpc and we argue that it is nearer than 9.8 kpc. If
      correct, our distance estimate lowers the total energy of the explosion and
      relaxes the demands on theoretical models. The energetics and the rapid decay of
      the radio source are not compatible with the afterglow model that is usually
      invoked for gamma-ray bursts. Instead, we suggest that the rapidly decaying radio
      emission arises from the debris ejected during the explosion.

PMID- 15858570
TI  - Observation of nuclear fusion driven by a pyroelectric crystal.
AB  - While progress in fusion research continues with magnetic and inertial
      confinement, alternative approaches--such as Coulomb explosions of deuterium
      clusters and ultrafast laser-plasma interactions--also provide insight into basic
      processes and technological applications. However, attempts to produce fusion in
      a room temperature solid-state setting, including 'cold' fusion and 'bubble'
      fusion, have met with deep scepticism. Here we report that gently heating a
      pyroelectric crystal in a deuterated atmosphere can generate fusion under desktop
      conditions. The electrostatic field of the crystal is used to generate and
      accelerate a deuteron beam (> 100 keV and >4 nA), which, upon striking a
      deuterated target, produces a neutron flux over 400 times the background level.
      The presence of neutrons from the reaction D + D --> 3He (820 keV) + n (2.45 MeV)
      within the target is confirmed by pulse shape analysis and proton recoil
      spectroscopy. As further evidence for this fusion reaction, we use a novel time
      of-flight technique to demonstrate the delayed coincidence between the outgoing
      alpha-particle and the neutron. Although the reported fusion is not useful in the
      power-producing sense, we anticipate that the system will find application as a
      simple palm-sized neutron generator.

PMID- 15858571
TI  - Increased productivity in the subantarctic ocean during Heinrich events.
AB  - Massive iceberg discharges from the Northern Hemisphere ice sheets, 'Heinrich
      events', coincided with the coldest periods of the last ice age. There is
      widespread evidence for Heinrich events and their profound impact on the climate
      and circulation of the North Atlantic Ocean, but their influence beyond that
      region remains uncertain. Here we use a combination of molecular fingerprints of
      algal productivity and radioisotope tracers of sedimentation to document eight
      periods of increased productivity in the subpolar Southern Ocean during the past
      70,000 years that occurred within 1,000-2,000 years of a Northern Hemisphere
      Heinrich event. We discuss possible causes for such a link, including increased
      supply of iron from upwelling and increased stratification during the growing
      season, which imply an alteration of the global ocean circulation during Heinrich
      events. The mechanisms linking North Atlantic iceberg discharges with
      subantarctic productivity remain unclear at this point. We suggest that
      understanding how the Southern Ocean was altered during these extreme climate
      perturbations is critical to understanding the role of the ocean in climate
      change.

PMID- 15858572
TI  - Electronic tagging and population structure of Atlantic bluefin tuna.
AB  - Electronic tags that archive or transmit stored data to satellites have advanced
      the mapping of habitats used by highly migratory fish in pelagic ecosystems. Here
      we report on the electronic tagging of 772 Atlantic bluefin tuna in the western
      Atlantic Ocean in an effort to identify population structure. Reporting
      electronic tags provided accurate location data that show the extensive
      migrations of individual fish (n = 330). Geoposition data delineate two
      populations, one using spawning grounds in the Gulf of Mexico and another from
      the Mediterranean Sea. Transatlantic movements of western-tagged bluefin tuna
      reveal site fidelity to known spawning areas in the Mediterranean Sea. Bluefin
      tuna that occupy western spawning grounds move to central and eastern Atlantic
      foraging grounds. Our results are consistent with two populations of bluefin tuna
      with distinct spawning areas that overlap on North Atlantic foraging grounds.
      Electronic tagging locations, when combined with US pelagic longline observer and
      logbook catch data, identify hot spots for spawning bluefin tuna in the northern
      slope waters of the Gulf of Mexico. Restrictions on the time and area where
      longlining occurs would reduce incidental catch mortalities on western spawning
      grounds.

PMID- 15858573
TI  - Learned kin recognition cues in a social bird.
AB  - In many cooperatively breeding birds, kin selection has an important role in the
      evolution and maintenance of social behaviour, and 'helpers' can maximize
      indirect fitness gains by preferentially allocating care to close relatives.
      Although there is evidence for kin-biased helping behaviour in several species,
      the mechanism of kin recognition underlying this behaviour is poorly understood.
      Vocalizations are the most commonly used cues in avian recognition systems, but
      the effectiveness of vocal signals as reliable recognition cues must depend on
      how they are acquired. However, there have been no experimental studies of the
      development of vocal recognition cues in cooperative birds; indeed, the ontogeny
      of all bird vocalizations other than song is poorly known in any species. Here,
      we show that cooperatively breeding long-tailed tits (Aegithalos caudatus) can
      discriminate between kin and non-kin according to the individual-specific
      characteristics of contact calls, and show experimentally that individuals learn
      these calls from provisioning adults during the nestling period. Finally, we show
      that the pattern of cooperative behaviour in this species is consistent with the
      use of recognition cues learned through association.

PMID- 15858574
TI  - A synthetic multicellular system for programmed pattern formation.
AB  - Pattern formation is a hallmark of coordinated cell behaviour in both single and
      multicellular organisms. It typically involves cell-cell communication and
      intracellular signal processing. Here we show a synthetic multicellular system in
      which genetically engineered 'receiver' cells are programmed to form ring-like
      patterns of differentiation based on chemical gradients of an acyl-homoserine
      lactone (AHL) signal that is synthesized by 'sender' cells. In receiver cells,
      'band-detect' gene networks respond to user-defined ranges of AHL concentrations.
      By fusing different fluorescent proteins as outputs of network variants, an
      initially undifferentiated 'lawn' of receivers is engineered to form a bullseye
      pattern around a sender colony. Other patterns, such as ellipses and clovers, are
      achieved by placing senders in different configurations. Experimental and
      theoretical analyses reveal which kinetic parameters most significantly affect
      ring development over time. Construction and study of such synthetic
      multicellular systems can improve our quantitative understanding of naturally
      occurring developmental processes and may foster applications in tissue
      engineering, biomaterial fabrication and biosensing.

PMID- 15858575
TI  - Dynamics of Drosophila embryonic patterning network perturbed in space and time
      using microfluidics.
AB  - Biochemical networks are perturbed both by fluctuations in environmental
      conditions and genetic variation. These perturbations must be compensated for,
      especially when they occur during embryonic pattern formation. Complex chemical
      reaction networks displaying spatiotemporal dynamics have been controlled and
      understood by perturbing their environment in space and time. Here, we apply this
      approach using microfluidics to investigate the robust network in Drosophila
      melanogaster that compensates for variation in the Bicoid morphogen gradient. We
      show that the compensation system can counteract the effects of extremely
      unnatural environmental conditions--a temperature step--in which the anterior and
      posterior halves of the embryo are developing at different temperatures and thus
      at different rates. Embryonic patterning was normal under this condition,
      suggesting that a simple reciprocal gradient system is not the mechanism of
      compensation. Time-specific reversals of the temperature step narrowed down the
      critical period for compensation to between 65 and 100 min after onset of
      embryonic development. The microfluidic technology used here may prove useful to
      future studies, as it allows spatial and temporal regulation of embryonic
      development.

PMID- 15858576
TI  - IKKalpha limits macrophage NF-kappaB activation and contributes to the resolution
      of inflammation.
AB  - Inflammation and innate immunity involve signalling pathways leading to the
      production of inflammatory mediators. Usually such responses are self-limiting,
      but aberrant resolution of inflammation results in chronic diseases. Much
      attention has focused on pro-inflammatory signalling but little is known about
      the mechanisms that resolve inflammation. The IkappaB kinase (IKK) complex
      contains two catalytic subunits, IKKalpha and IKKbeta, and controls the
      activation of NF-kappaB transcription factors, which play a pivotal role in
      inflammation. Ample evidence indicates that IKKbeta mediates NF-kappaB activation
      in response to pro-inflammatory cytokines and microbial products. IKKalpha
      regulates an alternative pathway important for lymphoid organogenesis, but the
      role of IKKalpha in inflammation is unknown. Here we describe a new role for
      IKKalpha in the negative regulation of macrophage activation and inflammation.
      IKKalpha contributes to suppression of NF-kappaB activity by accelerating both
      the turnover of the NF-kappaB subunits RelA and c-Rel, and their removal from pro
      inflammatory gene promoters. Inactivation of IKKalpha in mice enhances
      inflammation and bacterial clearance. Hence, the two IKK catalytic subunits have
      evolved opposing but complimentary roles needed for the intricate control of
      inflammation and innate immunity.

PMID- 15858577
TI  - Clathrin is required for the function of the mitotic spindle.
AB  - Clathrin has an established function in the generation of vesicles that transfer
      membrane and proteins around the cell. The formation of clathrin-coated vesicles
      occurs continuously in non-dividing cells, but is shut down during mitosis, when
      clathrin concentrates at the spindle apparatus. Here, we show that clathrin
      stabilizes fibres of the mitotic spindle to aid congression of chromosomes.
      Clathrin bound to the spindle directly by the amino-terminal domain of clathrin
      heavy chain. Depletion of clathrin heavy chain using RNA interference prolonged
      mitosis; kinetochore fibres were destabilized, leading to defective congression
      of chromosomes to the metaphase plate and persistent activation of the spindle
      checkpoint. Normal mitosis was rescued by clathrin triskelia but not the N
      terminal domain of clathrin heavy chain, indicating that stabilization of
      kinetochore fibres was dependent on the unique structure of clathrin. The
      importance of clathrin for normal mitosis may be relevant to understanding human
      cancers that involve gene fusions of clathrin heavy chain.

PMID- 15858578
TI  - A question of age.

PMID- 15858581
TI  - Scientists and societies. Planning for a positive postdoc.

PMID- 15858579
TI  - Thinking big Texas.

PMID- 15858584
TI  - Poster child.

PMID- 15858585
TI  - Getting the science and the ethics right in forensic genetics.

PMID- 15858588
TI  - Linking cilia to Wnts.

PMID- 15858589
TI  - Universal epistasis analysis.

PMID- 15858590
TI  - Mutation accumulation of the transcriptome.

PMID- 15858591
TI  - Epigenetics of hypertension in pregnancy.

PMID- 15858598
TI  - Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22
      genomic region.
AB  - Interferon-gamma, encoded by IFNG, is a key immunological mediator that is
      believed to play both a protective and a pathological role in malaria. Here, we
      investigate the relationship between IFNG variation and susceptibility to
      malaria. We began by analysing West African and European haplotype structure and
      patterns of linkage disequilibrium across a 100 kb genomic region encompassing
      IFNG and its immediate neighbours IL22 and IL26. A large case-control study of
      severe malaria in a West Africa population identified several weak associations
      with individual single-nucleotide polymorphisms in the IFNG and IL22 genes, and
      defined two IL22 haplotypes that are, respectively, associated with resistance
      and susceptibility. These data provide a starting point for functional and
      genetic analysis of the IFNG genomic region in malaria and other infectious and
      inflammatory conditions affecting African populations.

PMID- 15858599
TI  - Taq-I polymorphism in 3'UTR of the IL-12B and association with IL-12p40
      production from human PBMC.
AB  - A wide array of studies has demonstrated differences in genotype and allele
      frequencies of cytokine gene polymorphisms depending on ethnicity and race. In
      this study, the frequency of Taq-I polymorphism in 3' untranslated region of IL
      12B was investigated in two Bulgarian ethnic groups-Bulgarians and Turkish
      minority. No significant differences of genotype and allele frequencies were
      observed between these groups. Genotype distribution in the total group of
      Bulgarian citizens was: AA (61%), CA (32%) and CC (7%), and the allele frequency
      of 16974 A allele was 0.77. We also evaluated whether this polymorphism affects
      IL-12p40 production from human PBMC after stimulation. We demonstrated that
      association between genotype and IL-12p40 production by stimulated PBMC depends
      on the stimuli used. Our results indicated a significantly decreased IL-12 p40
      secretion for the following order of genotypes: AA>CA>CC, after stimulation of
      PBMC with C3-binding glycoprotein (C3bgp) in contrast to lipopolysaccharide,
      phytohaemagglutinin and pokeweed mitogen.

PMID- 15858600
TI  - Allelic effects on gene regulation at the autoimmunity-predisposing CTLA4 locus:
      a re-evaluation of the 3' +6230G>A polymorphism.
AB  - Genetic variation at a linkage disequilibrium block encompassing the cytotoxic T
      lymphocyte antigen-4 (CTLA4) gene influences susceptibility to autoimmunity, but
      identifying the polymorphism(s) responsible for this effect has been challenging.
      Recently, a single-nucleotide polymorphism (SNP) located 3' to the known
      polyadenylation site of CTLA4 (+6230G>A) and strongly associated with autoimmune
      disease was reported to regulate levels of soluble CTLA4 isoform (sCTLA4) but not
      the full-length isoform. The purpose of the present study is to define the
      mechanistic effect of the 3'SNP on the isoforms of CTLA4 (alternative splicing vs
      polyadenylation vs effects on RNA stability). However, using allele-specific
      single-nucleotide primer extension, we found no difference between mRNA
      transcripts derived from either +6230G>A allele in 11 heterozygous individuals,
      in either of the two known CTLA4 isoforms. We also found no effect of this
      polymorphism on ICOS (inducible costimulator), a putative downstream target. In
      addition, repeated attempts at 3' RACE (3'rapid amplification of cDNA ends) were
      unsuccessful in amplifying any contiguous sequence past the known CTLA4
      polyadenylation site and no such sequence was found in the EST databases. We
      conclude that the mechanism of the observed association of the +6230 SNP with
      autoimmune disease remains to be determined, but does not involve modulation of
      steady-state mRNA of any known CTLA4 isoform.

PMID- 15858601
TI  - Does a central MHC gene in linkage disequilibrium with HLA-DRB1*0401 affect
      susceptibility to type 1 diabetes?
AB  - Subtypes of HLA-DR4 are associated with susceptibility or protection against type
      1 diabetes (T1DM). We addressed whether this reflects linkage disequilibrium with
      the true susceptibility locus by studying broader MHC haplotypes marked by
      alleles of HLA-B, IKBL (adjacent to TNFA) and complement C4. The study used a
      largely Caucasian cohort from Western Australia. HLA-DRB1*0401 and HLA-DRB1*0405
      marked susceptibility to T1DM. In Caucasians, DRB1*0401 occurs predominantly in
      the 44.1 ancestral haplotype (AH; HLA-A2,B44, DRB1*0401,DQB1*0301) and the 62.1AH
      (HLA-A2,B15(62),DRB1*0401,DQB1*0302). HLA-B15 marked susceptibility and HLA-B44
      marked with resistance to T1DM in patients and controls preselected for HLA
      DRB1*0401. A gene between TNFA and HLA-B on the 8.1AH (HLA-A1,B8,;DR3,DQ2)
      modifies the effects of the class II alleles. Here, alleles characteristic of the
      62.1AH (C4B3, IKBL+446*T and HLA-A2,B15) were screened in donors preselected for
      HLA-DRB1*0401. C4B3 was associated with diabetes, consistent with a diabetes gene
      telomeric of MHC class II. However, increases in carriage of IKBL+446*T and HLA
      A2,B15 were marginal, as too few control subjects were available with the
      diabetogenic alleles. However, with these tools, selection of HLA-DRB1*0401,
      DQB1*0302 donors who are positive and negative for C4B3 will allow bidirectional
      mapping of diabetes genes in the central MHC.

PMID- 15858602
TI  - Lack of effect of L-carnitine supplementation on weight gain in very preterm
      infants.
AB  - OBJECTIVE: Carnitine transfer across the placenta occurs predominantly during the
      third trimester. Unless L-carnitine is provided, very preterm infants develop
      carnitine deficiency. Although breast milk and infant formulas contain L
      carnitine, parenteral nutrition solutions do not routinely provide L-carnitine.
      We hypothesized that prolonged L-carnitine supplementation in very preterm
      infants would improve weight gain and shorten length of stay in the hospital.
      STUDY DESIGN: The study was a double-blind parallel placebo-controlled randomized
      clinical trial. Eligible patients were <29 weeks of gestation, <72 hours of age,
      and did not have a potentially life-threatening congenital malformation or
      hereditary metabolic disorder. Patients were stratified by gestational age (23 to
      25(6/7) and 26 to 28(6/7) weeks), and randomized to receive, either L-carnitine
      at a dose of 50 mumol/kg/day, or placebo. Carnitine was provided intravenously
      until the infants tolerated 16 ml/day of feeds. The sample size was calculated to
      have 80% power to detect a 10% increase in weight gain from birth until 36 weeks
      of postmenstrual age or discharge from the hospital. Secondary outcome variables
      included food efficiency (defined as weight gain divided by caloric intake),
      weight gain at 4 weeks of age, time to regain birth weight and length of stay.
      RESULTS: Among the 63 infants enrolled in the trial, 32 were randomized to L
      carnitine and 31 to placebo. L-Carnitine supplementation did not significantly
      affect average daily weight gain from birth until 36 weeks or hospital discharge,
      or any of the secondary outcome variables. CONCLUSION: Prolonged supplementation
      of L-carnitine did not improve long-term weight gain in very preterm infants.

PMID- 15858603
TI  - Effect of bathing on skin flora of preterm newborns.
AB  - OBJECTIVE: To assess the effect of bathing with water only or with mild pH
      neutral soap and water on skin flora of preterm newborns. METHOD: Randomized
      blinded clinical trial that enrolled 73 preterm newborns whose gestational age
      was between 28 and 35 weeks and birth weight between 800 and 1800 g. At the age
      of 3 days the infants were randomly assigned to a group that was given daily
      baths either with water only, or with soap and water for 7 or more days.
      Antibiotic treatment delayed onset of the trial in some preterm infants. On the
      final day of bathing axillary bacterial cultures were obtained before and 30
      minutes after bathing. RESULTS: At the time of axillary culturing, the mean age
      of the newborns was 19 days. Coagulase-negative Staphylococcus was the most
      prevalent microorganism in both groups. No significant difference was found in
      the count of microorganism colonies between both groups. The comparison of the
      number of bacterial colonies between the time before and after bath, carried out
      by repeated-measures ANOVA showed a significant difference over time in the two
      groups, without a significant difference between the two groups. CONCLUSIONS:
      Bathing preterm newborns with water only or with soap and water produces similar
      effects on skin colonization of a preterm neonate. Both are effective to decrease
      the number of colonies of Gram-positive and Gram-negative bacteria.

PMID- 15858604
TI  - Neonatal - perinatal medicine fellowship training in long-term outcomes of
      neonatal intensive care unit graduates.

PMID- 15858605
TI  - Depression at birth in term infants exposed to maternal chorioamnionitis: does
      neonatal fever play a role?
AB  - OBJECTIVES: (1) To determine the incidence and the time course of elevated
      temperature following delivery in term infants with clinical chorioamnionitis
      (CHORIO) and (2) to determine if the extent of temperature elevation at birth is
      associated with increased likelihood of NICU Admissions, birth depression, or
      with short-term neurological abnormalities. DESIGN/METHODS: The infants were
      divided into two groups based on the median admission rectal temperature of 37.8
      degrees C for the cohort. Depression at birth was defined as either the need of
      positive pressure ventilation for >2 minutes, intubation, or Apgar score <6 at 5
      minutes. Neurological examination and assessment of encephalopathy (Sarnat
      staging) was performed at birth and daily thereafter, by one investigator blinded
      to temperature findings. RESULTS: Infants with higher rectal temperature at 30
      minutes of life were more likely to be admitted to NICU: OR (2.8, 95% confidence
      interval (CI) [1.8 to 4.3]), and were more likely to have birth depression OR (3,
      95% CI [1.4 to 6.5]). For infants in NICU, a rectal temperature above 37.8
      degrees C was present in 87% in the delivery room, persisted in 47% at 30
      minutes, and declined to a normal temperature at 60 minutes of life in the
      absence of medical interventions. There was no relationship between neurological
      scores and neonatal temperature. CONCLUSIONS: Term infants exposed to CHORIO who
      had a higher neonatal temperature at 30 minutes of life, were more likely to be
      admitted to the NICU and to have birth depression, than infants with lesser
      degree of temperature elevation after birth. Within the NICU group, the extent of
      temperature elevation was not associated with worse neurological outcomes.

PMID- 15858606
TI  - Work of breathing during nasal continuous positive airway pressure in preterm
      infants: a comparison of bubble vs variable-flow devices.
AB  - OBJECTIVE: To compare work of breathing and breathing asynchrony during bubble
      nasal continuous positive airway pressure (NCPAP) vs variable-flow (VF)-NCPAP in
      premature infants. STUDY DESIGN: We studied 18 premature infants of birth weight
      <1500 g who required NCPAP for mild respiratory distress. Each infant was studied
      on bubble and VF-NCPAP at 8, 6, 4, and 0 cm H2O. Tidal volumes were obtained by
      calibrated respiratory inductance plethysmography. Esophageal pressure estimated
      intrapleural pressure. Inspiratory and resistive work of breathing were
      calculated from pressure-volume data. Breathing asynchrony was assessed with
      phase angle. The results at all NCPAP levels were referenced to VF-NCPAP values
      at 8 cm H2O. RESULTS: Provision of NCPAP with either device decreased inspiratory
      work of breathing, tidal volume, and minute ventilation relative to NCPAP of 0 cm
      H2O. Bubble NCPAP did not decrease resistive work of breathing relative to 0 cm
      H2O. Resistive work of breathing (p=0.01), respiratory rate (p<0.03), and phase
      angle (p=0.002) were all greater with bubble compared to VF-NCPAP. CONCLUSION:
      The more labored and asynchronous breathing seen with bubble NCPAP may lead to
      higher failure rates over the long term than with VF-NCPAP.

PMID- 15858607
TI  - Congenital mesoblastic nephroma presenting with neonatal hypertension.

PMID- 15858609
TI  - RNAi therapy: dominant disease gene gets silenced.

PMID- 15858608
TI  - Lentivirus-mediated gene transfer of viral interleukin-10 delays but does not
      prevent cardiac allograft rejection.
AB  - Human immunodeficiency virus (HIV)-based lentiviral vectors expressing viral
      interleukin-10 (vIL-10) were used to transduce rat cardiac allografts with the
      aim of extending graft survival. vIL-10 expression was first shown, by RT-PCR, to
      persist in transduced heart isografts for at least 28 days after transduction.
      Cardiac transplants were performed in a fully allogeneic rat strain combination
      (Lewis to DA); allografts transduced by vectors expressing vIL-10 showed
      significantly prolonged survival (14.5 vs 7.5 days median survival time). Mixed
      lymphocyte reactions (MLRs) were used to determine the influence, in vitro, of
      vIL-10 on alloantigen-induced T-cell proliferation. Bioactive vIL-10, produced by
      DA rat aortic endothelial cells transduced with HIV-PGK-vIL-10, was added to MLRs
      at different time points and lymphocyte proliferation was assessed by uptake of
      [3H]thymidine. T-cell proliferation was inhibited by >80% when vIL-10 was added
      to the MLR at day 1, 2 or 3 of coculture. The inhibitory effect was significantly
      decreased when addition of vIL-10 was delayed until day 4 or 5 (47 and 35%
      inhibition, respectively). The extended graft survival time is comparable to that
      using adenoviral vectors delivering vIL-10 in a similar rat strain combination.
      The limited improvement in survival may be due to lack of inhibition of the early
      phase of the alloimmune response as suggested by in vitro studies confirming that
      maximum suppression of the MLR by vIL-10 can only be achieved if the cytokine is
      present at the initiation of alloimmune recognition. The delay in expression of
      vIL-10 from the lentiviral vector means that protocols must be developed to
      suppress the early stages of alloimmune stimulation before vIL-10 is produced.

PMID- 15858610
TI  - Efficient gene delivery to human and rodent islets with double-stranded (ds) AAV
      based vectors.
AB  - Transplantation of allogeneic pancreatic islets is an effective approach to treat
      type 1 diabetes. To bypass the need for systemic administration of
      immunosuppression drugs following transplantation, approaches to genetically
      modify allogeneic islets to express anti-inflammatory, immunosuppressive, or
      antiapoptotic proteins prior to transplantation are being developed. Adeno
      associated viral (AAV) based vectors have been used for gene transfer to islets,
      but the efficiency of functional transduction is low. Recently, double-stranded
      (ds) or double-copy (dc) based AAV vectors have been developed that allow for
      more rapid and efficient AAV-mediated transgene expression following
      transduction. Here we demonstrate that intact human and murine islets can be
      transduced with dsAAV2-eGFP efficiently compared to single-stranded AAV2-eGFP.
      Furthermore, our results demonstrate that murine islets transduced with dsAAV2
      eGFP have normal islet glucose responsiveness, viability, and islet insulin
      content. Transplantation of the dsAAV2-eGFP transduced islet restored normal
      glycemia in diabetic mice without eliciting an immune response. Significant
      dsAAV2-mediated eGFP expression was observed in the islet grafts for at least 6
      months post-transplant. Finally, we demonstrated that dsAAV serotypes 2, 6, and 8
      infect human islets efficiently. Taken together, these results suggest that dsAAV
      based vectors are highly appropriate for gene transfer to islets to facilitate
      transplantation.

PMID- 15858611
TI  - Filgrastim and alemtuzumab (Campath-1H) for refractory chronic lymphocytic
      leukemia.
AB  - Alemtuzumab (anti-CD52; Campath-1H) is effective in fludarabine-refractory
      chronic lymphocytic leukemia (CLL), but is associated with infection and early
      onset neutropenia. To reduce toxicity, filgrastim (G-CSF) was administered
      concurrently with alemtuzumab. In total, 14 CLL patients (median age 59) with a
      median of 3.5 prior regimens (range 1--12) received i.v. alemtuzumab, stepped up
      from 3 to 30 mg the first week, then 30 mg thrice weekly for 12 weeks. Filgrastim
      5 microg/kg was administered daily 5 days before and throughout alemtuzumab
      therapy. Six patients developed cytomegalovirus (CMV) reactivation 3--6 weeks
      into treatment; six patients developed fever, three neutropenia, and one
      pneumonia. The patient with CMV pneumonia died; ganciclovir cleared CMV in the
      other patients. Five patients developed early neutropenia (weeks 2--5). Four
      patients developed delayed neutropenia (weeks 10--13) unassociated with CMV
      reactivation. Nine patients ceased therapy because of infectious and hematologic
      toxicity. Five partial responses were noted, all in patients with lymph nodes>cm,
      lasting a median of 6.5 months (range 5--13). Filgrastim and alemtuzumab were
      given concurrently with manageable infusion toxicity and clinical activity, but
      the efficacy of this regimen was limited by delayed neutropenia of unclear
      etiology and CMV reactivation. Filgrastrim should not be administered
      prophylactically during alemtuzumab therapy outside clinical trials.

PMID- 15858612
TI  - Centrosome aberrations--hen or egg in cancer initiation and progression?

PMID- 15858613
TI  - Centrosome aberrations in chronic myeloid leukemia correlate with stage of
      disease and chromosomal instability.
AB  - Centrosome abnormalities are hallmarks of various cancers and have been
      implicated in chromosome missegregation, chromosomal instability, and aneuploidy.
      Since genetic instability is a common feature in chronic myeloid leukemia (CML),
      we sought to investigate whether centrosome aberrations occur and correlate with
      disease stage and cytogenetic findings in CML. We examined 34 CML samples
      including CD 34+Ph+cells of 18 newly diagnosed patients (chronic phase (CP)) and
      16 blast crisis (BC) specimens by using a centrosome-specific antibody to
      pericentrin. All CP and BC samples displayed centrosome alterations as compared
      with corresponding CD 34+control cells. Centrosome abnormalities were detected in
      29.1+/-5.9% of CP blasts and in 54.3+/-4.8% of BC blasts, but in only 2.4+/-1.1%
      of controls (P<0.0001). Additional karyotypic alterations to the t(9;22)
      translocation were found in only 1/18 CML-CP patients. In contrast, 11/16 (73%)
      CML-BC patients displayed additional karyotype alterations in 48.7% of analyzed
      cells, correlating with an abnormal centrosome status (P=0.0005). Our results
      indicate that centrosome defects are a common and early detectable feature in CML
      that may contribute to acquisition of chromosomal aberrations and aneuploidy.
      They may be considered as the driving force of disease progression and could
      serve as future prognostic markers.

PMID- 15858614
TI  - Predicting the effect of transcription therapy in hematologic malignancies.
AB  - Molecular lesions of genes encoding for transcriptional regulatory proteins are
      common oncogenic events in hematologic malignancies. Transcriptional activation
      and repression both occur by virtue of the choreographed recruitment of
      multisubunit cofactor complexes to target gene loci. As a consequence, the three
      dimensional structure of the target gene is altered and its potential to support
      transcription is increased or decreased. The complexity of the transcriptional
      process offers a rich substrate for designing therapeutic agents. The objective
      of such 'transcription therapy' is to regain control over cohorts of target genes
      and restore the normal genetic and epigenetic programming of the cancer cell. The
      success of all-trans retinoic acid in the treatment of acute promyelocytic
      leukemia indicates that transcription therapy can be highly effective and safe. A
      classification scheme of these therapeutic strategies is proposed herein, which
      allows predictions to be made regarding specificity, efficacy, disease spectrum
      and side effects. This framework could help facilitate discussion of the
      mechanisms of action of transcription therapy drugs as well as the design of
      preclinical and clinical trials in the future.

PMID- 15858615
TI  - Antimyeloma activity of two novel N-substituted and tetraflourinated thalidomide
      analogs.
AB  - Thalidomide alone or in combination with steroids has significant activity in
      multiple myeloma (MM). However, given its teratogenic potential, analogs have
      been synthesized, retaining the anti-MM activity without these side effects. We
      examined the anti-MM activity of two thalidomide analogs, CPS11 and CPS49. Direct
      cytotoxicity of the drugs on myeloma cell lines and patient myeloma cells was
      examined using thymidine uptake. Tumor cell apoptosis was evaluated by flow
      cytometry as well as Western blotting for caspase and PARP cleavage. Cellular
      signaling events were examined by immunoblotting for phosphorylated proteins.
      Both drugs inhibit proliferation of several MM cell lines sensitive and resistant
      to conventional therapies. They decrease secretion of IL-6, IGF, and VEGF by
      marrow stromal cells. Importantly, they inhibit proliferation of MM cells
      adherent to stromal cells. These drugs induce caspase-mediated apoptosis in MM
      cell lines, as well as patient MM cells. They inhibit the PI3K/Akt and JAK/STAT
      (signal transducers and activators of transcription) pathways in MM cells and are
      antiangiogenic in matrigel-based assays. CPS11 and CPS49 have potent antimyeloma
      activity and can overcome protective effects of the tumor microenvironment. They
      have potent antiangiogenic activity and direct effect on bone marrow stroma.
      These encouraging preclinical data provide the basis for further evaluation in
      the clinic.

PMID- 15858616
TI  - Abl inhibitor BMS354825 binding mode in Abelson kinase revealed by molecular
      docking studies.

PMID- 15858617
TI  - TEL/AML 1 real-time quantitative reverse transcriptase PCR can complement minimal
      residual disease assessment in childhood ALL.

PMID- 15858618
TI  - Durability of molecular remission in chronic myeloid leukemia patients treated
      with imatinib vs allogeneic stem cell transplantation.

PMID- 15858619
TI  - High expression of lipoprotein lipase in poor risk B-cell chronic lymphocytic
      leukemia.
AB  - We investigated the pattern of lipoprotein lipase (LPL) expression in B-cell
      chronic lymphocytic leukemia (B-CLL) and assessed its prognostic relevance.
      Expression of LPL mRNA as well as protein was highly restricted to leukemic B
      cells. The intensity of intracellular immunoreactivity of LPL was higher in
      samples of patients with unmutated immunoglobulin heavy-chain variable region
      genes (IGV(H)) compared to those with mutated IGV(H) genes. LPL mRNA levels in
      peripheral blood mononuclear cells (PBMNC) from 104 CLL patients differed by 1.5
      orders of magnitude between cases with mutated (N=51) or unmutated (N=53) IGV(H)
      (median: 1.33 vs 45.22 compared to normal PBMNC). LPL expression correlated
      strongly with IGV(H) mutational status (R=0.614; P<0.0001). High LPL expression
      predicted unmutated IGV(H) status with an odds ratio of 25.90 (P<0.0001) and
      discriminated between mutated and unmutated cases in 87 of 104 patients (84%).
      LPL expression was higher in patients with poor risk cytogenetics. High LPL
      expression was associated with a shorter treatment-free survival (median 40 vs 96
      months, P=0.001) and a trend for a shorter median overall survival (105 months vs
      not reached). Our data establish LPL as a prognostic marker and suggest
      functional consequences of LPL overexpression in patients with B-CLL.

PMID- 15858620
TI  - Building a body of evidence.

PMID- 15858621
TI  - A curious mind.

PMID- 15858622
TI  - A current perspective on medical informatics and health sciences librarianship.
AB  - OBJECTIVE: The article offers a current perspective on medical informatics and
      health sciences librarianship. NARRATIVE: The authors: (1) discuss how
      definitions of medical informatics have changed in relation to health sciences
      librarianship and the broader domain of information science; (2) compare the
      missions of health sciences librarianship and health sciences informatics,
      reviewing the characteristics of both disciplines; (3) propose a new definition
      of health sciences informatics; (4) consider the research agendas of both
      disciplines and the possibility that they have merged; and (5) conclude with some
      comments about actions and roles for health sciences librarians to flourish in
      the biomedical information environment of today and tomorrow. SUMMARY: Boundaries
      are disappearing between the sources and types of and uses for health information
      managed by informaticians and librarians. Definitions of the professional domains
      of each have been impacted by these changes in information. Evolving definitions
      reflect the increasingly overlapping research agendas of both disciplines.
      Professionals in these disciplines are increasingly functioning collaboratively
      as "boundary spanners," incorporating human factors that unite technology with
      health care delivery.

PMID- 15858623
TI  - Information-seeking behaviors of practitioners in a primary care practice-based
      research network (PBRN).
AB  - OBJECTIVE: The aim of this study was to examine the information-seeking behaviors
      (e.g., information resource usage patterns, access to types of sources and to
      medical libraries, and use of particular information technologies) of members in
      a primary care practice-based research network (PBRN) to inform future efforts
      supporting primary care practitioners in their daily care of patients. METHODS:
      Every primary care practitioner who was a member of the Kentucky Ambulatory
      Network-including family practitioners, general practitioners, nurse
      practitioners, and physician assistants-was surveyed. The cross-sectional survey
      included twenty-six questions to investigate the information-seeking behavior of
      primary care practitioners. RESULTS: The response rate was 51% (59 of 116). Most
      practitioners (58%) stated they sought information to support patient care
      several times per week, and most (68%) noted they do this while the patient
      waited. Many practitioners (40%) never or almost never perform literature
      searches from online sources such as MEDLINE, although 44% said they did so a few
      times per month. A significant correlation between use of online sources and use
      of print sources suggests that those who seek online information more frequently
      than those who do not also seek information from print sources frequently, and
      vice versa. Access to medical libraries was also reported as high. CONCLUSIONS:
      Consistent with previous studies, the primary care practitioners in this rural
      PBRN reported more frequent use of print and interpersonal sources compared to
      online sources. There appeared to be, however, a clear difference between those
      practitioners who are more likely to seek information, regardless of format, and
      those who are less inclined. Future interventions will need to address such
      barriers as time, cost, and information-seeking skills.

PMID- 15858624
TI  - Information-seeking behavior of nursing students and clinical nurses:
      implications for health sciences librarians.
AB  - OBJECTIVES: This research was conducted to provide new insights on clinical
      nurses' and nursing students' current use of health resources and libraries and
      deterrents to their retrieval of electronic clinical information, exploring
      implications from these findings for health sciences librarians. METHODS:
      Questionnaires, interviews, and observations were used to collect data from
      twenty-five nursing students and twenty-five clinical nurses. RESULTS: Nursing
      students and clinical nurses were most likely to rely on colleagues and books for
      medical information, while other resources they frequently cited included
      personal digital assistants, electronic journals and books, and drug
      representatives. Significantly more nursing students than clinical nurses used
      online databases, including CINAHL and PubMed, to locate health information, and
      nursing students were more likely than clinical nurses to report performing a
      database search at least one to five times a week. CONCLUSIONS AND
      RECOMMENDATIONS: Nursing students made more use of all available resources and
      were better trained than clinical nurses, but both groups lacked database
      searching skills. Participants were eager for more patient care information, more
      database training, and better computer skills; therefore, health sciences
      librarians have the opportunity to meet the nurses' information needs and improve
      nurses' clinical information-seeking behavior.

PMID- 15858625
TI  - Online journals' impact on the citation patterns of medical faculty.
AB  - PURPOSE: The purpose was to determine the impact of online journals on the
      citation patterns of medical faculty. This study looked at whether researchers
      were more likely to limit the resources they consulted and cited to those
      journals available online rather than those only in print. SETTING: Faculty
      publications from the college of medicine at a large urban university were
      examined for this study. The faculty publications from a regional medical college
      of the same university were also examined in the study. The number of online
      journals available for faculty, staff, and students at this institution has
      increased from an initial core of 15 online journals in 1998 to over 11,000
      online journals in 2004. METHODOLOGY: Searches by author affiliation were
      performed in the Web of Science to find all articles written by faculty members
      in the college of medicine at the selected institution. Searches were conducted
      for the following years: 1993, 1996, 1999, and 2002. Cited references from each
      faculty-authored article were recorded, and the corresponding cited journals were
      coded into four categories based on their availability at the institution in this
      study: print only, print and online, online only, and not owned. Results were
      analyzed using SPSS. RESULTS: The number of journals cited per year continued to
      increase from 1993 to 2002. The results did not indicate that researchers were
      more likely to cite online journals or were less likely to cite journals only in
      print. At the regional location where the number of print-only journals was
      minimal, use of the print-only journals did decrease in 2002, although not
      significantly. CONCLUSION/DISCUSSION: It is possible that electronic access to
      information (i.e., online databases) has had a positive impact on the number of
      articles faculty will cite. Results of this study suggest, at this point, that
      faculty are still accessing the print-only collection, at least for research
      purposes, and are therefore not sacrificing quality for convenience.

PMID- 15858626
TI  - Personal digital assistant-based drug information sources: potential to improve
      medication safety.
AB  - OBJECTIVES: This study compared the potential for personal digital assistant
      (PDA)-based drug information sources to minimize potential medication errors
      dependent on accurate and complete drug information at the point of care.
      METHODS: A quality and safety framework for drug information resources was
      developed to evaluate 11 PDA-based drug information sources. Three drug
      information sources met the criteria of the framework: Eprocrates Rx Pro, Lexi
      Drugs, and mobileMICROMEDEX. Medication error types related to drug information
      at the point of care were then determined. Forty-seven questions were developed
      to test the potential of the sources to prevent these error types. Pharmacists
      and physician experts from Creighton University created these questions based on
      the most common types of questions asked by primary care providers. Three
      physicians evaluated the drug information sources, rating the source for each
      question: 1=no information available, 2=some information available, or 3 =
      adequate amount of information available. RESULTS: The mean ratings for the drug
      information sources were: 2.0 (Eprocrates Rx Pro), 2.5 (Lexi-Drugs), and 2.03
      (mobileMICROMEDEX). Lexi-Drugs was significantly better (mobileMICROMEDEX t test;
      P=0.05; Eprocrates Rx Pro t test; P=0.01). CONCLUSION: Lexi-Drugs was found to be
      the most specific and complete PDA resource available to optimize medication
      safety by reducing potential errors associated with drug information. No resource
      was sufficient to address the patient safety information needs for all cases.

PMID- 15858627
TI  - Adoption of structured abstracts by general medical journals and format for a
      structured abstract.
AB  - BACKGROUND: The use of a structured abstract has been recommended in reporting
      medical literature to quickly convey necessary information to editors and
      readers. The use of structured abstracts increased during the mid-1990s; however,
      recent practice has yet to be analyzed. OBJECTIVES: This article explored actual
      reporting patterns of abstracts recently published in selected medical journals
      and examined what these journals required of abstracts (structured or otherwise
      and, if structured, which format). METHODS: The top thirty journals according to
      impact factors noted in the "Medicine, General and Internal" category of the ISI
      Journal Citation Reports (2000) were sampled. Articles of original contributions
      published by each journal in January 2001 were examined. Cluster analysis was
      performed to classify the patterns of structured abstracts objectively. Journals'
      instructions to authors for writing an article abstract were also examined.
      RESULTS: Among 304 original articles that included abstracts, 188 (61.8%) had
      structured and 116 (38.2%) had unstructured abstracts. One hundred twenty-five
      (66.5%) of the abstracts used the introduction, methods, results, and discussion
      (IMRAD) format, and 63 (33.5%) used the 8-heading format proposed by Haynes et
      al. Twenty-one journals requested structured abstracts in their instructions to
      authors; 8 journals requested the 8-heading format; and 1 journal requested it
      only for intervention studies. CONCLUSIONS: Even in recent years, not all
      abstracts of original articles are structured. The eight-heading format was
      neither commonly used in actual reporting patterns nor noted in journal
      instructions to authors.

PMID- 15858628
TI  - High school peer tutors teach MedlinePlus: a model for Hispanic outreach.
AB  - OBJECTIVES: The objective was to introduce the MedlinePlus Website to the
      predominantly Hispanic residents of the Lower Rio Grande Valley region of Texas
      by partnering with a health professions magnet high school (known as Med High).
      METHODS: Community assessment was used in the planning stages and included pre
      project focus groups with students and teachers. Outreach methods included peer
      tutor selection, train-the-trainer sessions, school and community outreach, and
      pre- and posttests of MedlinePlus training sessions. Evaluation methods included
      Web statistics; end-of-project interviews; focus groups with students, faculty,
      and librarians; and end-of-project surveys of students and faculty. RESULTS: Four
      peer tutors reached more than 2,000 people during the project year. Students and
      faculty found MedlinePlus to be a useful resource. Faculty and librarians
      developed new or revised teaching methods incorporating MedlinePlus. The project
      enhanced the role of school librarians as agents of change at Med High. The
      project continues on a self-sustaining basis. CONCLUSIONS: Using peer tutors is
      an effective way to educate high school students about health information
      resources and, through the students, to reach families and community members.

PMID- 15858629
TI  - Using volunteers in Ontario hospital libraries: views of library managers.
AB  - BACKGROUND: Volunteers have been a resource for all types of libraries for many
      years. Little research has been done to describe the attitudes librarians have
      toward library volunteers. More specifically, the attitudes of hospital
      librarians toward volunteers have never been studied. OBJECTIVE: The objective
      was to explore and describe the extent of volunteer use and to determine library
      managers' attitudes toward volunteers. DESIGN, SETTING, AND PARTICIPANTS: An
      anonymous, self-report 38-item questionnaire was mailed to the target population
      of 89 hospital library managers in Ontario. Seventy-nine useable questionnaires
      were analyzed from an adjusted sample of 86 eligible respondents, resulting in a
      response rate of 92%. SPSS 11.5 was used to analyze the data. FINDINGS: The data
      revealed the attitudes of managers using volunteers did not differ significantly
      from the attitudes of managers not using volunteers. The findings showed that a
      majority of managers did not believe their libraries were adequately staffed with
      paid employees. Sufficient evidence was found of an association between a
      manager's belief in the adequacy of staffing in the library and the use of
      volunteers in the library (chi2(1, N=76)=4.11, P=0.043). Specifically, volunteers
      were more likely to be used by managers who did not believe their libraries were
      adequately staffed. The presence of a union in the library and the use of
      volunteers were also associated (chi2(1, N=77)=4.77, P=0.029). When unions were
      present in the library, volunteers were less likely to be used. IMPLICATIONS:
      This research has implications for hospital library managers in the management of
      volunteers. Volunteers should not be viewed as a quick fix or as a long-term
      solution for a library's understaffing problem.

PMID- 15858630
TI  - Learning to use learning resources during medical school and residency.
AB  - OBJECTIVES: This study (1) examined the natural history of learning to use
      learning resources by medical students and residents and (2) considered whether
      that history is consistent with the ways in which physicians approach their
      learning tasks. METHODS: The authors conducted and analyzed thirty-two open-ended
      interviews of first-year and third-year medical students and first-year and
      senior residents in internal medicine, family medicine, or pediatrics. RESULTS
      AND DISCUSSION: Learning to use learning resources occurs at the same time as
      learning done to address instructional and clinical problems that physicians-in
      training face, with all kinds of learning following well-documented stages.
      Skills for using resources are developed gradually and by overcoming barriers
      such as time constraints and existing habits. CONCLUSIONS: Implications of the
      natural history of learning to use learning resources can be employed by
      librarians and medical teachers to facilitate self-directed learning for
      physicians-in-training. Specific recommendations are provided.

PMID- 15858631
TI  - Staff development planning in an academic health sciences library.
AB  - OBJECTIVE: A staff development committee (SDC) was convened to implement staff
      development opportunities for an academic health sciences library system
      comprised of three separate facilities. The charge for the SDC was to: (1)
      develop programs to enhance workplace skills and personal growth, (2) communicate
      the availability of existing programs at the university and medical center, and
      (3) encourage the staff to participate in these opportunities. PROGRAM: The
      committee created goals and objectives and developed a survey designed to give
      staff the opportunity to provide input for this initiative. With an 80% response
      rate, the survey results were used to plan 15 events based on staff needs and
      preferences. First-year attendance for SDC-sponsored events was 459. Committee
      members served as liaisons for each event. Two forms were developed to facilitate
      event planning. A monthly announcement sheet, email reminders, and the library's
      local area network are used to communicate upcoming SDC events and encourage
      attendance. CONCLUSION: This approach can serve as a useful model for similar
      program planning in any organization.

PMID- 15858632
TI  - F2F connection: a community health information needs assessment of Texas families
      who have children with chronic illnesses and/or disabilities and their care
      providers.

PMID- 15858633
TI  - Standards for hospital libraries 2002 with 2004 revisions.

PMID- 15858634
TI  - Genetic alphabetic order: what came before A?

PMID- 15858635
TI  - Lectins: tools for the molecular understanding of the glycocode.
AB  - Recent progress in glycobiology has revealed that cell surface oligosaccharides
      play an essential role in recognition events. More precisely, these saccharides
      may be complexed by lectins, carbohydrate-binding proteins other than enzymes and
      antibodies, able to recognise sugars in a highly specific manner. The ubiquity of
      lectin-carbohydrate interactions opens enormous potential for their exploitation
      in medicine. Therefore, extraordinary effort is made into the identification of
      new lectins as well as into the achievement of a deep understanding of their
      functions and of the precise mechanism of their association with specific
      ligands. In this review, a summary of the main features of lectins, particularly
      those found in legumes, will be presented with a focus on the mechanism of
      carbohydrate-binding. An overview of lectin-carbohydrate interactions will also
      be given, together with an insight into their energetics. In addition,
      therapeutic applications of lectins will be discussed.

PMID- 15858636
TI  - Memory of chirality in intramolecular conjugate addition of enolates: a novel
      access to nitrogen heterocycles with contiguous quaternary and tertiary
      stereocenters.
AB  - Nitrogen heterocycles with contiguous quaternary and tertiary stereocenters have
      been prepared in high enantiomeric purity by intramolecular conjugate addition of
      enolates generated from alpha-amino acid derivatives via memory of chirality.

PMID- 15858637
TI  - Alkylation of natural endoperoxide G3-factor. Synthesis and antimalarial activity
      studies.
AB  - Alkylation of the peroxyhemiketal function is described and all synthesised
      endoperoxides show good antimalarial activity. New rearrangement reactions in the
      presence of CsCO3, and preliminary results on Fe(II) chemical reduction of the O
      O bond are presented.

PMID- 15858638
TI  - Visual sensing of Ca2+ ion via photoreaction of fluorenyl ester-armed cyclen.
AB  - Fluorenyl ester-armed cyclen gave fluorenone and related decomposition compounds
      upon photoirradiation. The reaction was effectively suppressed by the formation
      of an octacoordinated Ca2+ complex while Na+ and other alkali/alkaline earth
      metal cations had little influence. Since the production efficiency of
      fluorescent fluorenone related well to the concentration of the Ca2+ ion, the
      photoreaction of this armed cyclen offered the naked-eye detection of Ca2+ ion in
      aqueous samples.

PMID- 15858639
TI  - Solvent-free mechanochemical and one-pot reductive benzylizations of
      malononitrile and 4-methylaniline using Hantzsch 1,4-dihydropyridine as the
      reductant.
AB  - Under mechanical milling conditions, direct reductive benzylizations of
      malononitrile and 4-methylaniline by aromatic aldehydes were achieved using a
      Hantzsch 1,4-dihydropyridine as the reductant.

PMID- 15858640
TI  - DABCO catalyzed addition of selenosulfonates to alpha,beta-unsaturated ketones.
AB  - In the presence of DABCO (30 mol%), the addition of various selenosulfonates to
      alpha,beta-unsaturated ketones proceeded smoothly to give the corresponding
      adducts in good yields under mild conditions.

PMID- 15858641
TI  - A new method for the synthesis of acyltitanium complexes and their application to
      copper-mediated acylmetallation of carbon-carbon multiple bonds in aqueous media.
AB  - Treatment of alpha, beta-unsaturated carbonyl compounds or methyl propargyl ether
      with acylchlorobis(cyclopentadienyl)titanium in the presence of triethylamine and
      a copper salt in aqueous THF resulted in acylation of the carbon-carbon multiple
      bond, yielding the corresponding 1,4-diketones in good yields.

PMID- 15858642
TI  - The effect of the anion on the physical properties of trihalide-based N,N
      dialkylimidazolium ionic liquids.
AB  - Low viscosity, high density trihalide-based 1-n-butyl-3-methylimidazolium ionic
      liquids have been prepared and characterised. Key physical properties (density,
      conductivity, melting point, refractive index, surface tension and diffusion
      coefficient) of the ionic liquids have been determined and are compared with
      those of other 1,3-dialkylimidazolium molten salts. The relationship between
      anion identity and the physical properties of the ionic liquids under
      investigation is discussed.

PMID- 15858643
TI  - Cyclohexane bis-urea compounds for the gelation of water and aqueous solutions.
AB  - A new class of efficient hydrogelators has been developed by a simple
      modification of the peripheral substituents of cyclohexane bis-urea
      organogelators with hydrophilic hydroxy or amino functionalities. These bis-urea
      hydrogelators were synthesised in two or three steps using an alternative
      procedure to the common isocyanate method. Gelation was obtained with organic
      solvents, water and strongly basic aqueous solutions like 25% ammonia.
      Hydrogelation was found to depend on a delicate balance between the
      hydrophobicity of the alkyl chains, hydrophilicity of the terminal substituents
      and the enantiomeric purity of the compound. The hydrogels consisted of a network
      of fibers, in which all urea groups are involved in intermolecular hydrogen
      bonding. Most likely, gelation is driven by hydrophobic interactions of the
      methylene units, whereas hydrogen bond formation between the urea groups provides
      the necessary anisotropy of the aggregation and the high thermal stability of the
      gels.

PMID- 15858644
TI  - The reaction of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) with the angiotensin
      converting enzyme inhibitor, captopril--mechanism of transnitrosation.
AB  - Kinetic studies involving the use of both stopped-flow and diode array
      spectrophotometers, show that the reaction between SNAP and captopril in the
      presence of the metal ion sequestering agent, EDTA, occurs in two well-defined
      stages. The first stage is a fast reaction while the second stage is slow. The
      first stage has been postulated to be transnitrosation, and the second stage
      involves the decay of the newly formed RSNO to effect nitric oxide (NO) release.
      Both stages are found to be dependent on captopril and H+ concentration. The
      rates of the transnitrosation increased drastically with increasing pH in the
      first stage, signifying that the deprotonated form of captopril is the more
      reactive species. In the case of the second stage the variation in pH showed an
      increase in rate up to pH 8 after which the rate remained unchanged. Both stages
      were clearly distinguishable and easily monitored separately. Transnitrosation is
      a reversible reaction with the tendency for the equilibrium to break down at high
      thiol concentration. Second-order rate constants were calculated based on the
      following derived expressions: 
      d[SNAP]/dt=k(f)((K(SHCapSH)[CapSH](t))/(K(SHCapSH)+[H+]))[SNAP]. k(f) is the
      second-order rate constant for the forward reaction of the reversible
      transnitrosation process. At 37 degrees C, k(f)= 785 +/- 14 M(-1) s(-1),
      activation parameters [Delta]H(f)++= 49 +/- 2 kJ mol(-1), (Delta)S(f)++=-32 +/- 2
      J K(-1) mol(-1). The activation parameters demonstrate the associative nature of
      the transnitrosation mechanism. The second stage has been found to be very
      complex, as a variety of nitrogen products form as predicted before. However, the
      following expression was derived from the initial kinetic data: rate
      =k1K[SNOCap][CapS-]/(K[CapS-]+ 1) to give k1= 13.3 +/- 0.4 x 10(-4) s(-1) and K=
      5.59 +/- 0.53 x 10(4) M(-1), at 37 degrees C, where k1 is the first-order rate
      constant for the decay of the intermediate formed during the reaction between
      SNOCap and the remaining excess CapSH present at the end of the first stage
      reaction. Activation parameters are (Delta)H1++= 37 +/- 1 kJ mol(-1),
      (Delta)S1++=-181 +/- 44 J K(-1) mol(-1).

PMID- 15858645
TI  - Correlation of bilayer membrane cation transport and biological activity in alkyl
      substituted lariat ethers.
AB  - Dialkyldiaza-18-crown-6 lariat ethers having twin n-octyl, n-decyl, n-dodecyl, n
      tetradecyl, n-hexadecyl, 1-oxodecyl and 1-oxododecyl side arms were prepared and
      studied. Cation transport in liposomes mediated by these compounds showed
      discontinuous activity that correlated with toxicity to the bacteria E. coli and
      B. Subtilis, and the yeast S. Cerevisiae. Transport, toxicity and membrane
      depolarization studies all suggest that side chain length affords very different
      interactions in a bilayer membrane compared with bulk phases. An explanation for
      activity in terms of carrier transport and restricted transverse relaxation is
      proposed.

PMID- 15858646
TI  - Synthesis and triplex forming properties of pyrrolidino pseudoisocytidine
      containing oligodeoxynucleotides.
AB  - Pyrrolidino pseudo-C-nucleosides are isosteres of natural deoxynucleosides which
      are protonated at the pyrrolidino ring nitrogen under physiological conditions.
      As constituents of a triplex forming oligodeoxynucleotide (TFO), the positive
      charge is expected to stabilise DNA triple helices via electrostatic interactions
      with the phosphodiester backbone of the target DNA. We describe the synthesis of
      the pyrrolidino isocytidine pseudonucleoside and the corresponding
      phosphoramidite building block and its incorporation into TFOs. Such TFOs show
      substantially increased DNA affinity compared to unmodified
      oligodeoxynucleotides. The increase in affinity is shown to be due to the
      positive charge at the pyrrolidino subunit.

PMID- 15858647
TI  - Arginine magic with new counterions up the sleeve.
AB  - The elusive questions how arginine-rich sequences allow peptides and proteins to
      penetrate cells or to form voltage-gated ion channels are controversial topics of
      current scientific concern. The possible contributions of exchangeable
      counterions to these puzzling processes remain underexplored. The objective of
      this report is to clarify scope and limitations of certain counteranions to
      modulate cellular uptake and anion carrier activity of oligo/polyarginines. The
      key finding is that the efficiency of counteranion activators depends
      significantly on many parameters such as activator-membrane and activator-carrier
      interactions. This finding is important because it suggests that counteranions
      can be used to modulate not only efficiency but also selectivity. Specifically,
      activator efficiencies are found to increase with increasing aromatic surface of
      the activator, decreasing size of the transported anion, increasing carrier
      concentration as well as increasing membrane fluidity. Efficiency sequences
      depend on membrane composition with coronene > pyrene >>fullerene > calix[4]arene
      carboxylates in fluid and crystalline DPPC contrasting to fullerene >
      calix[4]arene approximately coronene > pyrene carboxylates in EYPC with or
      without cholesterol or ergosterol. In HeLa cells, the efficiency of planar
      activators (pyrene) exceeds that of spherical activators (fullerenes,
      calixarenes). Polyarginine complexes with pyrene and coronene activators exhibit
      exceptional excimer emission. Decreasing excimer emission with increasing ionic
      strength reveals dominant hydrophobic interactions with the most efficient
      carboxylate activators. Dominance of ion pairing with the inefficient high
      affinity sulfate activators is corroborated by the reversed dependence on ionic
      strength. These findings on activator-carrier and activator-membrane interactions
      are discussed as supportive of arene-templated guanidinium-carboxylate pairing
      and interface-directed translocation as possible origins of the superb
      performance of higher arene carboxylates as activators.

PMID- 15858649
TI  - Proton di-ionizable p-tert-butylcalix[4]arene-crown-6 compounds in cone, partial
      cone and 1,3-alternate conformations: synthesis and alkaline earth metal cation
      extraction.
AB  - Novel proton di-ionizable p-tert-butylcalix[4]arene-crown-6 compounds in cone,
      partial-cone and 1,3-alternate conformations are synthesized to compare the
      efficiency and selectivity with which they extract alkaline earth metal ions. In
      these ligands, a crown-6 polyether unit links alternate aromatic rings of the
      calix[4]arene framework. To the remaining lower-rim positions are attached
      oxyacetic acid or N-(X)sulfonyl oxyacetamide groups. Changing the conformation
      varies the spatial relationship between a polyether-complexed divalent metal ion
      and the ionized side arms of the ligands. This is found to markedly affect the
      efficiency and selectivity in competitive solvent extraction of alkaline earth
      metal ions from aqueous solutions into chloroform by the di-ionizable
      calix[4]arene-crown-6 ligands.

PMID- 15858648
TI  - First enantioselective synthesis of (-)- and (+)-virgatusin, tetra-substituted
      tetrahydrofuran lignan.
AB  - The first highly enantioselective syntheses of tetra-substituted tetrahydrofuran
      lignan, (-)- and (+)-virgatusin, were achieved. Hemiacetal was stereoselectively
      obtained from Evans's syn-aldol product as a single isomer. This hemiacetal was
      converted to (-)-virgatusin via hydrogenolysis. (+)-Virgatusin was also
      synthesized through the same process. The enantiomeric excess of the both
      enantiomers was determined as more than 99% ee.

PMID- 15858650
TI  - beta-Selective synthesis of 2'-deoxy-5,6-dihydro-4-thiouridine, a precursor of
      the unstable nucleoside product of ionising radiation damage 2'-deoxy-5,6
      dihydrocytidine.
AB  - 4-Thio oxathiaphosphepane nucleosides - undergo a rearrangement in pyridine that
      leads selectively to the beta anomer of the 2'-deoxy-5,6-dihydro-4-thiouridine
      derivative . This diastereoselective reaction proceeds through a multistep
      mechanism initiated by the addition of pyridine at the C1'position of - and
      concomitant opening of the oxathiaphosphepane. This was confirmed by the trapping
      of the corresponding intermediate in the closely related DMAP series. In
      contrast, LR thiation of in pyridine leads to a new class of modified nucleosides
      containing an oxathiaphospholane moiety. The quantitative conversion of into the
      corresponding 5,6-dihydrocytosine derivative with NH3-MeOH is also reported.

PMID- 15858651
TI  - Biosynthesis of the allene (-)-marasin in Marasmius ramealis.
AB  - [1-14C]-E-dehydromatricaria methyl ester and dimethyl [1-14C]-deca-4,6,8-triyne
      1,10-dioate are incorporated into the allene (-)-marasin in Marasmius ramealis
      without scrambling of the 14C label. This and the levels of the incorporations
      (0.8% and 4.9% respectively) strongly suggests that the above esters, or close
      relatives, can be converted directly into (-)-marasin in M. ramealis, and that
      the diyne-allene moiety in this latter compound arises by the rearrangement,
      under enzymic control, of an alkyltriyne moiety.

PMID- 15858652
TI  - On the activation of valerolactam with triflic anhydride: the synthesis of omega
      trifluorosulfonamido dipeptides using a transpeptidation reaction under mild
      conditions.
AB  - The activation of valerolactam with triflic anhydride is studied in detail,
      initially producing an O-triflated lactam, which rearranges, following the
      addition of base at higher temperatures, to an N-triflated derivative. This
      reacts with a series of nucleophiles to produce esters and amides, which are
      formally dipeptides of omega-amino acids.

PMID- 15858653
TI  - Synthesis and evaluation of the glycosidase inhibitory activity of 5-hydroxy
      substituted isofagomine analogues.
AB  - An efficient strategy for the synthesis of 5-hydroxy substituted isofagomine
      analogues and , having both -CH2OH/CH3 and -OH functionality at the C-5 position,
      and evaluation of their inhibitory potency is reported. The synthetic methodology
      involves the aldol-Cannizzaro reaction of easily available alpha-d
      xylopentodialdose followed by hydrogenolysis to afford the triol . Selective
      amidation of the alpha- and beta-hydroxymethyl group at C-4, deprotection of the
      1,2-acetonide group and hydrogenation gave the target molecules, which were found
      to be potent against beta-glycosidases with IC50 values in the micro molar range.
      Compound showed excellent potency against glycosidases and human salivary
      amylase.

PMID- 15858654
TI  - Optical glucose detection across the visible spectrum using anionic fluorescent
      dyes and a viologen quencher in a two-component saccharide sensing system.
AB  - A very general system is described in which anionic fluorescent dyes possessing a
      wide range of absorbance and emission wavelengths are used in combination with a
      boronic acid-modified viologen quencher to sense glucose at pH 7.4 in buffered
      aqueous solution. The present study demonstrates this capability with the use of
      eleven anionic fluorescent dyes of various structural types. Signal modulation
      occurs as the monosaccharide binds to the viologen quencher and alters its
      efficiency in quenching the fluorescence of the anionic dyes. The degree of
      quenching and the magnitude of the glucose signal were found to correlate roughly
      with the number of anionic groups on the dye. Optimal quencher : dye ratios were
      determined for each dye to provide a fairly linear signal in response to changes
      in glucose concentration across the physiological range.

PMID- 15858655
TI  - 1,N6-Etheno-7-deaza-2,8-diazaadenosine: syntheses, properties and conversion to 7
      deaza-2,8-diazaadenosine.
AB  - 1,N6-Etheno-7-deaza-2,8-diazaadenosine (4) was synthesized from 8-aza-7
      deazaadenosine (6) in 64% overall yield. The starting material 6 was obtained by
      the direct glycosylation of 8-aza-7-deazaadenine (7) with 1-O-acetyl-2,3,5-tri-O
      benzoyl-beta-d-ribofuranose (8) (NO2 CH3, BF3 x Et2O; 77% yield). Compound 4 was
      transformed into 7-deaza-2,8-diazaadenosine (5). The fluorescence of compound 4
      shows an emission maximum at 531 nm (phosphate buffer; pH 7.0), which is
      bathochromically shifted compared to 1,N(6)-etheno-2-azaadenosine (3a) (495 nm).
      A conformational analysis was performed in the solid state and in solution.

PMID- 15858656
TI  - Assembly intermediates in polyketide biosynthesis: enantioselective syntheses of
      beta-hydroxycarbonyl compounds.
AB  - A versatile approach for the enantioselective synthesis of functionalised beta
      hydroxy N-acetylcysteamine thiol esters has been developed which allows the
      facile incorporation of isotopic labels. It has been shown that a remarkable
      reversal of selectivity occurs in the titanium mediated aldol reaction of
      acyloxazolidinone using either (S)- or (R)-tert-butyldimethylsilyloxybutanal. The
      aldol products are valuable intermediates in the synthesis of 4-hydroxy-6
      substituted delta-lactones.

PMID- 15858657
TI  - Asymmetrized tris(hydroxymethyl)methane as a precursor of N- and O-containing 6
      membered heterocycles through ring-closing metathesis.
AB  - A novel synthetic application of asymmetrized tris(hydroxymethyl)methane (THYM),
      obtained in both enantiomeric forms in high e.e. via a chemoenzymatic procedure,
      is described. Starting from the common precursor , N- and O-containing 6-membered
      heterocycles have been prepared exploiting ring-closing metathesis as the key
      step. Possible elaborations of the double bond in and have been explored and, in
      the case of , conversion into the glycosidase inhibitor isofagomine has been
      achieved.

PMID- 15858658
TI  - Synthesis of aminocyclopentanols: alpha-D-galacto configured sugar mimics.
AB  - Four aminocyclopentanols, as mimics of putative intermediates in the hydrolysis
      of alpha-d-galactosides, have been synthesized through a number of
      stereoselective transformations using the cis-fused cyclopentane-1,4-lactone (1R,
      5S, 7R, 8R)-7,8-dihydroxy-2-oxabicyclo[3.3.0]oct-3-one as a chiral building
      block. The compounds were tested towards various glycosidases but showed no
      anomer selectivity in the inhibition of alpha- and beta-galactosidases.

PMID- 15858659
TI  - Powder-to-powder polycondensation of natural saccharides. Facile preparation of
      highly branched polysaccharides.
AB  - Solid-state polycondensation of a natural saccharide was found to take place in
      the presence of H3PO4(5 mol%) at 110 degrees C under a N2 flow, giving a highly
      branched polysaccharide (conv. 11-84%, Mw = 1400-19000, Mn = 1200-3700); the
      reaction mixture was powdery throughout the polymerization. Interestingly, alpha-
      and beta-anomers showed different polymerization behaviour; the former was
      polymerized more slowly, however, they gave comparable molecular weight polymers.
      The polysaccharide product was per-O-methylated and subjected to structure
      analyses. The acid-hydrolysis products, the partially O-methylated
      monosaccharides, suggested that the polysaccharide products have highly branched
      structures. MALDI-TOF mass analysis revealed that intramolecular glycosylation
      and acetal exchange reactions are involved in the polymerization mechanism.

PMID- 15858660
TI  - Solvent effects in the interaction of methyl-beta-cyclodextrin with
      solvatochromic merocyanine dyes.
AB  - The UV-vis spectroscopic behavior of dyes: 2,6-diphenyl-4-(2,4,6
      triphenylpyridinium-1-yl)phenolate (1) and 4-[(1-methyl-4(1H)-pyridinylidene)
      ethylidene]-2,5-cyclohexadien-1-one (2) was investigated in solutions of methyl-
      beta-cyclodextrin (methyl-beta-CyD), using water, methanol, ethanol, propan-2-ol,
      butan-1-ol, acetone, acetonitrile, N,N-dimethylformamide (DMF), dimethyl
      sulfoxide (DMSO), N,N-dimethylacetamide (DMA), chloroform and dichloromethane as
      solvents. In aqueous solutions of dye (2) the addition of M-beta-CD leads to a
      bathochromic shift (of the maximum absorption), showing that the probe was
      transferred to a microenvironment of lower polarity and suggesting the formation
      of a 1 : 1 dye (2) : CyD inclusion complex, with a binding constant of 128.5 +/-
      3.5 dm(3) mol(-1). Data for dye 2 in alcohols showed hypsochromic shifts, which
      increased in the following order: methanol < ethanol < propan-2-ol < butan-1-ol.
      These observations appear to reflect dye-solvent interactions through hydrogen
      bonding. If dye-solvent interactions are strong, the CyD-dye interactions are
      consequently weak, but the latter increase in importance when the dye-solvent
      interaction becomes weaker. With hydrogen-bond accepting solvents, data for both
      dyes showed clearly increasing hypsochromic shifts following the order: DMSO <
      DMA < DMF < acetone < acetonitrile. This order is exactly the inverse of the
      increasing order of basicity of the medium. This indicates that the dominant
      factor for the observed effects in these solvents is the solvent-CyD interaction
      through hydrogen bonding involving the hydroxyl groups of the CyD and the basic
      groups of the solvents. These interactions diminish in intensity if the basic
      character of the medium is reduced, increasing the capability of the dye to
      interact with the CyD using its phenoxide donor moiety. The largest hypsochromic
      shifts were obtained in chloroform (66.0 nm) and dichloromethane (67.5 nm) with
      dye after addition of methyl-beta-CyD. In these specific situations, solvents
      display weak basic and acid properties, that enhanced CyD-dye interactions to
      such an extent that association complexes formed through hydrogen bonding could
      be detected (K11) values of 24.8 +/- 4.9 dm3 mol(-1) in dichloromethane and 66.1
      +/- 8.0 dm3 mol(-1) in chloroform).

PMID- 15858661
TI  - Factors affecting the selection of products from a photochemically generated
      singlet biradical.
AB  - The chemistries of a monoradical of the ultrafast "radical-clock" type and a
      structurally related singlet biradical, generated by Norrish type II
      photochemistry, are compared. The monoradical is found to undergo the
      characteristic ring-opening reaction of its class at about 10(10) s(-1) at room
      temperature. However, the singlet biradical shows no evidence of the analogous
      ring-opening reaction. The contrasting chemistry is traced not to a fundamental
      difference in electronic structure of the two intermediates, but rather to a
      steric interaction that the biradical alone would have to suffer during the ring
      opening. Although the magnitude of the steric hindrance is small (estimated 15-20
      kJ mol(-1)), it is enough to shut down the reaction, because the biradical has
      other facile product-forming reactions available.

PMID- 15858662
TI  - Selective synthesis of C-arylglycosides via Cp*RuCl-catalyzed partially
      intramolecular cyclotrimerizations of C-alkynylglycosides.
AB  - In the presence of catalytic amounts of Cp*RuCl(cod), the partially
      intramolecular cyclotrimerizations of various C-alkynylglycosides and C
      diynylglycosides proceeded at ambient temperature to afford C-arylglycosides.

PMID- 15858663
TI  - Determining the sigma-donor ability of the cyclopropane C-C bond.
AB  - The low temperature crystal structures of ester and ether derivatives of varying
      electron demand, derived from cyclopropylmethanol and dicyclopropylmethanol ,
      have been determined. These structures show a very strong response of the C-OR
      bond distance to the electron demand of the OR substituent, demonstrating the
      strong sigma-donor ability of the strained C-C bonds in the cyclopropane ring.

PMID- 15858664
TI  - Modification and structure-activity relationship of a small molecule HIV-1
      inhibitor targeting the viral envelope glycoprotein gp120.
AB  - This paper describes selected modification and structure-activity relationship of
      the small molecule HIV-1 inhibitor, 4-benzoyl-1-[(4-methoxy-1H-pyrrolo[2,3
      b]pyridin-3-yl)oxoacetyl]-2-(R)-methylpiperazine (BMS-378806). The results
      revealed: i) that both the presence and configuration (R vs. S) of the 3-methyl
      group on the piperazine moiety are important for the antiviral activity, with the
      3-(R)-methyl derivatives showing the highest activity; ii) that the
      electronegativity of the C-4 substituent on the indole or azaindole ring seems to
      be important for the activity, with a small, electron-donating group such as a
      fluoro or a methoxy group showing enhanced activity, while a nitro group
      diminishes the activity; iii) that the N-1 position of the indole ring is not
      eligible for modification without losing activity; and iv) that bulky groups
      around the C-4 position of the indole or azaindole ring diminish the activity,
      probably due to steric hindrance in the binding. We found that a synthetic
      bivalent compound with two BMS-378806 moieties being tethered by a spacer
      demonstrated about 5-fold enhanced activity in an nM range against HIV-1
      infection than the corresponding monomeric inhibitor. But the polyacrylamide
      based polyvalent compounds did not show inhibitory activity at up to 200 nM.

PMID- 15858665
TI  - Fluorometric sensing of alkali metal and alkaline earth metal cations by novel
      photosensitive monoazacryptand derivatives in aqueous micellar solutions.
AB  - Novel monoazacryptand-type fluorescent chemosensors, (derived from an 18-crown-6)
      and (derived from a 15-crown-5) both with a pyrene ring as their photoresponsive
      moiety, were synthesized. Their fluorescence properties for alkali metal and
      alkaline earth metal cations in water were then examined. The detection of metal
      cations was accomplished by a change in the fluorescence intensity of the host
      compounds, based on a photoinduced electron transfer (PET) mechanism. In aqueous
      solution, showed little fluorescence upon the addition of Ba2+ because of the
      very weak complexation with Ba2+, but the presence of micelles of
      polyoxyethylene(10) isooctylphenyl ether (Triton X-100) enabled to show highly
      sensitive and selective Ba2+ detection among alkali metal and alkaline earth
      metal cations. With respect to the selective fluorescent detection of important
      metal cations (Na+, K+, Mg2+, Ca2+) relevant to living organisms, was found to
      detect K+ with high selectivity in aqueous micellar solutions of
      polyoxyethylene(20) sorbitan monostearate (Tween-60). The selectivity for metal
      cations was mainly dependent on the goodness of fit of the host cavity and the
      metal cation size. In the presence of anionic surfactants, detected alkaline
      earth metal cations more effectively than alkali metal cations.

PMID- 15858666
TI  - Synthesis of screening substrates for the directed evolution of sialic acid
      aldolase: towards tailored enzymes for the preparation of influenza A sialidase
      inhibitor analogues.
AB  - The stereoselective synthesis of two epimeric screening substrates, (4R, 5R, 6R)-
      and (4S, 5R, 6R)-6-dipropylcarbamoyl-2-oxo-4,5,6-trihydroxy-hexanoic acid, for
      the directed evolution of sialic acid aldolase is described. The complementary
      methods relied on stereoselective indium-mediated additions of ethyl alpha
      bromomethyl acrylate to functionalised aldehydes. With an alpha-hydroxy aldehyde,
      (2R, 3R)-2,3-dihydroxy-4-oxo butanoic acid dipropylamide, the addition was
      chelation controlled, and the syn product, (6R, 5R, 4S)-6-dipropylcarbamoyl-2
      methylidene-4,5,6-trihydroxy-hexanoic acid ethyl ester, was obtained. In
      contrast, the stereochemical outcome of the addition to (2R, 3R)-N,N-dipropyl-2,3
      O-isopropylidene-4-oxobutyramide was consistent with Felkin-Anh control, and the
      anti adduct, (4R, 5R, 6R)-6-dipropylcarbamoyl-2-methylidene-4-hydroxy-5,6-O
      isopropylidene-hexanoic acid ethyl ester, was the major product. Ozonolysis and
      deprotection gave the screening substrates as mixtures of furanose and pyranose
      forms, in good yields.

PMID- 15858667
TI  - [End-of-life care in pediatrics: much more than a fight against entropy].

PMID- 15858668
TI  - [Toxocariasis and asthma: a relevant association].

PMID- 15858669
TI  - [Otitis media: an age-old problem, but a current issue of contention].

PMID- 15858670
TI  - [Bronchopulmonary dysplasia].
AB  - OBJECTIVE: To present a wide-ranging review of the literature on broncopulmonary
      dysplasia, covering new definitions, pathophysiology, prevention, treatment,
      prognosis and progression. SOURCES OF DATA: The most relevant articles published
      on the subject since it was first described in 1967 were selected from MEDLINE
      search results. SUMMARY OF THE FINDINGS: Bronchopulmonary dysplasia is considered
      one of the primary causes of chronic lung disease among infants. It is associated
      with frequent and prolonged hospital admissions, in particular for pulmonary
      diseases, with high rates of mortality and alterations to neuropsychomotor
      development and pondero-statural growth. Pathogenesis is complex, being primarily
      influenced by prematurity, infection, supplementary oxygen and mechanical
      ventilation. Prevention involves appropriate prenatal care, the prevention of
      premature delivery, prenatal corticosteroids, surfactant replacement therapy and
      "protective" ventilatory strategies. Treatment of bronchopulmonary dysplasia
      patients demands a multidisciplinary team. When indicated, oxygen supplementation
      is extremely important. Despite increased risk of morbidity and mortality during
      the first years of life, long term progress is favorable in the majority of
      cases. CONCLUSIONS: Bronchopulmonary dysplasia has been and continues to be
      studied in great depth with the objective of identifying its causes and possible
      prevention and treatment strategies. Controversies remain with respect of these
      issues and also about the prognosis of these patients, in particular when the
      subject is long-term progress of "new" bronchopulmonary dysplasia patients.

PMID- 15858671
TI  - [Life support limitation at three pediatric intensive care units in southern
      Brazil].
AB  - OBJECTIVES: To describe causes of death and factors involved in the decision
      making process related to life support limitation at three university-affiliated
      pediatric intensive care units in the south of Brazil. METHODS: A retrospective
      study was conducted, based on a review of the medical records of all deaths
      occurring during 2002 at three pediatric intensive care units in Porto Alegre.
      Three previously trained pediatric fellows from each service performed the study.
      Data were assessed relating to general case characteristics, causes of death
      (failed cardiopulmonary resuscitation, brain death, do-not-resuscitate orders,
      withholding or withdrawing life-sustaining treatment -- the last three modes were
      classified as the life support limitation group), length of stay in hospital, end
      of-life plans and the participation of patients families and Ethics Committees.
      The Student t test, Mann Whitney, chi-square, odds ratio and multivariate
      analyses were used for comparisons. RESULTS: Close to 53.3% of fatal cases had
      received full cardiopulmonary resuscitation. The incidence of life support
      limitation was 36%, with statistical differences (p = 0.014) between the three
      hospitals (25 versus 54.3 and 45.5%, respectively). The most frequent form of
      life support limitation was a do-not-resuscitate order (70%). Life support
      limitation was associated with the presence of chronic disease (odds ratio = 8.2;
      95%CI 3.2-21.3) and length stay in the pediatric intensive care unit (odds ratio
      = 4.4; 95%CI 1.6-11.8). The rate of involvement of families and Ethics Committees
      in the decision-making process was lesser than 10%. CONCLUSIONS: Cardiopulmonary
      resuscitation is offered more frequently than is observed in northern countries.
      In contrast, life support limitation is offered through do-not-resuscitate
      orders. These findings and the low participation of the families in the decision
      making process reflect the difficulties to be overcome by those professionals who
      are responsible for handling critically ill children in southern Brazil.

PMID- 15858672
TI  - [A profile of the medical conduct preceding child death at a tertiary hospital].
AB  - OBJECTIVE: To study the profile of care provided to pediatric patients suffering
      fatal outcomes at a university hospital, including: description of models,
      comparisons between units, associated factors, participants involved and records
      of decisions made. METHODS: Cross-sectional study. One of the investigators
      reviewed the medical and nursing records of deceased patients. Interviews were
      held and questionnaires filled out with the care team members over a period of 12
      months (May 1, 2002 to April 30, 2003). RESULTS: The study included 106 cases.
      The most frequent treatment patterns at the hospital were: withholding advanced
      life support (51.9%) and unsuccessful cardiopulmonary resuscitation (44.3%). The
      decision to make a do-not-resuscitate order occurred later in the intensive care
      unit (p < 0.05). The restricted care category was more prevalent in the neonatal
      unit and among patients with chronic diseases that limit survival (p < 0.05). The
      professionals that most often participated in the decision-making process were
      the unit s treating physician and resident (52.8%) and the medical team (31.1%).
      Parents or guardians were observed to have been involved in 20.8% of cases. For
      the entire hospital, seven cases (6.6%) of ambiguous or discordant
      cardiopulmonary resuscitation procedures were found. CONCLUSIONS: Procedures
      involving limitation of therapy are frequent, especially in the neonatal unit.
      Diagnosis of brain death and withdrawal of advanced life support are,
      nevertheless, rare. Decisions to grant do-not-resuscitate orders are generally
      mate late, especially in the intensive care unit. In this sample procedures for
      full participation in decisions and for recording decisions were imperfect.

PMID- 15858673
TI  - [Clinical-epidemiological study of toxocariasis in a pediatric population].
AB  - OBJECTIVE: The variety of toxocariasis clinic manifestations and its relationship
      with asthma motivated this study. The aim was to study T.canis seropositivity at
      a public pediatric service and its association with laboratory, epidemiological
      and clinical factors. METHODS: This study was cross-sectional and controlled. Two
      hundred and eight children, from 1 to 14 years old and treated at the University
      of Santo Amaro Pediatric Department s Immunology and Pneumology clinic between
      January 2000 and January 2001, underwent serology testing. Antibodies were
      detected by ELISA testing for the larval excretory-secretory antigen of T. canis.
      We used the chi-square test for T.canis seropositivity (titers > or = 1:320)
      associations with: puppies at home, contact with soil, geophagia, onicophagia,
      mother's educational level, asthma, chronic cough, repetitive pneumonia, skin
      manifestations, rhinitis, hepatomegaly, splenomegaly, abdominal pain, anemia,
      eosinophilia, immunoglobulins, parasitosis and stunted growth. The Kruskal-Wallis
      variance analysis method was used for mean comparisons between seropositive and
      seronegative groups. Significance was set at p < or = 0.05. RESULTS:
      Seroprevalence was 54.8%, with a mean age of 6.5 years while for seronegative
      children the mean age was 5.8 years, showing no significant difference. There was
      also no difference between sexes. Seropositivity was significantly associated
      with puppies at home, contact with soil, hepatomegaly, asthma, eosinophilia,
      increased serum immunoglobulin (Ig) E levels and stunted growth. CONCLUSION:
      Seroprevalence was elevated in this study . T.canis infection must be considered
      in at-risk children, such as those with puppies at home, who have had contact
      with soil, who have hepatomegaly and/or asthma with eosinophilia and increased
      serum IgE.

PMID- 15858674
TI  - [Secretion of middle ear in infants -- occurrence, recurrence and related
      factors].
AB  - OBJECTIVE: The present study aimed at evaluating the occurrence and recurrence of
      middle ear secretion and possible associated factors in the first two years of
      life of 190 newborns and infants, participants in the interdisciplinary
      prevention, detection, and intervention program at the Clinica de Educacao para
      Saude of Universidade do Sagrado Coracao. METHODS: Newborns and infants were
      monthly submitted to anamnesis, otoscopy, behavioral hearing assessment using
      sound instruments and pure tones (pediatric audiometry) and tympanometry.
      RESULTS: The results revealed that 68.4% of infants presented one or more
      episodes of middle ear secretion during their two first years, with more
      recurrence among males. Peak occurrence was between four and 12 months of age
      and, the earlier the first episode, the higher the probability of recurrence.
      Greatest incidence was during May and August. It was found that, of the variables
      investigated, the period of exclusive breastfeeding actuated as a protector
      factor. With respect of risk factors, it was observed that passive smoking,
      gastro-esophageal reflux and respiratory allergy were related with the
      recurrences of effusion. CONCLUSION: Findings revealed the importance of periodic
      auditory follow-up for infants during their first two years of life, considered
      to be the critical period of auditory system maturation, during which sensory
      deprivation can be responsible for damage to the development of speech, language
      and other auditory abilities.

PMID- 15858675
TI  - [Prospects for genetic hearing loss screening: 35delG mutation tracking in a
      newborn population].
AB  - OBJECTIVES: To investigate the prevalence of the 35delG mutation in a newborn
      population, with specific molecular testing, and to evaluate the prospects for
      genetic neonatal screening for hearing impairment. POPULATION AND METHOD: 233
      newborn were evaluated at the Hospital de Base de Sao Jose do Rio Preto, SP, for
      molecular analysis of the 35delG mutation in the connexin 26 gene, with the
      reaction technique in allele-specific polymerase chain reaction, after genomic
      DNA extraction from umbilical cord blood. RESULTS: Five heterozygotes were
      identified, obtaining a prevalence of 2.24% of 35delG mutation carriers in the
      study population. CONCLUSION: Using the molecular test allowed for the
      identification of the 35delG mutation in the study population with the
      possibility of being used as a complement to neonatal audiometric screening as
      being simple, fast, and easily to perform with low costs.

PMID- 15858676
TI  - [Prevalence of systemic inflammatory syndromes at a tertiary pediatric intensive
      care unit].
AB  - OBJECTIVE: To assess the prevalence of systemic inflammatory syndromes on
      admission to a tertiary-care university pediatric intensive care unit (ICU), and
      relate this to length of hospital stay, risk of death and mortality rate.
      METHODS: Cross-sectional, prospective, observational study, including all
      patients admitted to the Hospital de Clinicas de Porto Alegre (HCPA) ICU between
      August 1st 1999 and July 31st 2000. Patient demographic variables were considered
      together with the risk of mortality on admission, co-morbidities, length of
      hospital stay and ICU outcome, in addition to variables that characterize the
      systemic inflammatory syndromes (systemic inflammatory response syndrome, sepsis,
      severe sepsis and septic shock). RESULTS: We studied 447 admissions of 388
      patients; 54% were male, with a median age of 20 months. The prevalence of
      systemic inflammatory response syndrome (SIRS) was 68%: 2/3 infectious (sepsis,
      severe sepsis or septic shock) and 1/3 non-infectious. Risk of mortality scores
      for patients with infectious SIRS were higher than for those with non-infectious
      SIRS (6.75% [P25 = 2.25 - P75 = 21.3] vs. 2.35% [P25 = 1.1 - P75 = 6.7]; p = 0)
      and increased according to SIRS severity (2.9; 10.85, 43.9%; p < 0.05). The
      observed mortality was 12% for patients with SIRS and 5.8% for those without SIRS
      (p = 0.057); the observed mortality for infectious SIRS was 14.9% and for non
      infectious 6.3% (p = 0.041). The period spent in ICU for infectious SIRS was
      longer than for non-infectious cases: 3 days (P25 = 2 - P75 = 7) vs. 2 days (P25
      = 1.5 - P75 = 4); p = 0.006. CONCLUSIONS: The prevalence rate of patients with
      systemic inflammatory response syndrome upon admission to HCPA pediatric
      intensive care unit was elevated, with a predominance of infectious syndromes,
      responsible for longer stays, increased risk of mortality and increased mortality
      of patients during the period evaluated.

PMID- 15858677
TI  - [Nasopharyngeal colonization by Streptococcus pneumoniae in children with sickle
      cell disease receiving prophylactic penicillin].
AB  - OBJECTIVES: To determine the prevalence of nasopharyngeal pneumococcus
      colonization in children with sickle cell disease undergoing penicillin
      prophylaxis, to identify risk factors for colonization and to serotype and
      determine antibiotic resistance in pneumococci obtained from those children.
      METHODS: Between April 9, 2002 and February 28, 2003, 188 nasopharyngeal swabs
      were obtained from 98 children with sickle cell disease in follow-up at the
      Hospital Sao Paulo-Universidade Federal de Sao Paulo. Pneumococci were isolated
      and identified by standard methods. The minimal inhibitory concentration for
      penicillin was determined by the E-test method. Isolates were serotyped with the
      use of type-specific antisera for 46 different serotypes (Neufeld-Quellung
      reaction). RESULTS: The age of children ranged from 4 months to 17 years (median
      and standard deviation 6.8-/+4.7 years). Thirteen of the 98 children had
      nasopharyngeal pneumococcus colonization (13.3% prevalence). There was a
      significantly greater risk of colonization among children less than 2 years old
      (p = 0.02). Twenty-one percent of isolates had intermediate penicillin
      resistance. There were no isolates highly resistant to penicillin. All isolates
      were susceptible to erythromycin, ceftriaxone, or vancomycin. The most frequently
      identified serotypes were 18C and 23F. CONCLUSIONS: Penicillin prophylaxis
      reduced pneumococcal nasopharyngeal colonization and did not increase the
      prevalence of penicillin-resistant pneumococci in children with sickle cell
      disease. Penicillin can be used not only for prophylaxis, but also in the acute
      management of febrile states with these children.

PMID- 15858678
TI  - [Pulmonary lesions and total parenteral nutrition in children admitted to a
      pediatric intensive care unit].
AB  - OBJECTIVE: To describe lung injuries in autopsied pediatric patients (neonates
      through 15 years old) subjected or not to total parenteral nutrition, in an
      intensive care unit. METHODS: Sections from six paraffin-embedded lung fragments,
      from 114 children were studied by routine staining. Demographic, clinical and
      therapeutic data were retrieved from the records. Statistical analysis was
      performed using Statistical Package for the Social Sciences. RESULTS: The 114
      patients were divided in two groups: 50 who were treated with total parenteral
      nutrition with lipid emulsion and 64 who did not receive total parenteral
      nutrition. The two groups did not differ in gender (p = 0.654), age (p = 0.682)
      or body weight (p = 0.175), but duration of hospital stay (p = 0.000),
      prematurity (p = 0.008) and treatment with blood products (p = 0.009) were all
      higher in the group treated with total parenteral nutrition. All patients
      received mechanical ventilation during hospitalization. Chi-square comparisons
      showed that diffuse alveolar injury (p = 0.022), pulmonary fibrosis (p = 0.019),
      pneumocyte hyperplasia (p = 0.004), microthromboembolism (p = 0.047) and
      thrombophlebitis (0.033) all exhibited a significant relationship with total
      parenteral nutrition. However, a multivariate analysis by logistic regression,
      taking into account prematurity and duration of hospital stay, demonstrated that
      total parenteral nutrition was an independent factor only with respect of
      pulmonary fibrosis. CONCLUSION: Although lung injuries were significantly more
      frequent in children who had received total parenteral nutrition, it was
      impossible to conclude that the lipid infusion had a direct relationship with
      these injuries, because prematurity and duration of hospital stay were
      significant co-factors.

PMID- 15858679
TI  - [Plasma vitamin A levels in deprived children with pneumonia during the acute
      phase and after recovery].
AB  - OBJECTIVE: The aim of this study was to examine the plasma retinol of children in
      the acute phase of pneumonia and after recovery and to investigate the
      association between plasma levels of retinol after recovery with socioeconomic
      variables, nutritional status and severity of pneumonia. METHODS: A prospective
      cohort study which included 40 low-income hospitalized children with pneumonia,
      aged 6 months to 5 years. We evaluated: plasma retinol level during the acute
      phase and after recovery, years of schooling of the head of the family, per
      capita income, birth weight, nutritional status, hemoglobin levels and severity
      of pneumonia. RESULTS: Mean plasma retinol levels were significantly higher after
      recovery than during the acute phase of infection (1.4+/-0.6 vs. 1.7+/-0.6
      micromol/l, p = 0.03). The frequency of inadequate plasma retinol levels (< 1.05
      micromol/l) was 32.5 and 17.5% for the acute phase and after recovery,
      respectively. There were no statistically significant associations between plasma
      retinol deficiency and the clinical and epidemiological variables studied. More
      severe pneumonia was observed in 30/40 (75%) of the patients. There was no
      statistically significant association between plasma retinol inadequacy after
      recovery and severity of pneumonia (4/30 - 13.3% vs. 3/10 - 30.0%, p = 0.34).
      CONCLUSION: Serum retinol levels were significantly higher after recovery than
      during the acute phase of pneumonia. There was no statistically significant
      association between the deficiency of serum retinol and the clinical and
      epidemiological variables studied.

PMID- 15858680
TI  - [Prevalence of iron deficiency and its association with vitamin A deficiency in
      preschool children].
AB  - OBJECTIVES: To identify the prevalence of iron deficiency in the population
      studied, as well as verifying if such deprivation is associated with vitamin A
      deficiency. METHODS: One hundred seventy-nine children, > or = 24 months and < 72
      months of age, with no diarrhea and/or fever at collection were studied. Vitamin
      A deficiency identification was carried out through serum 30-day dose-response
      test. Samples of peripheral blood from fasting children was obtained for
      hemoglobin counts, serum iron, and unsaturated iron binding capacity assays.
      Information about the presence of diarrhea and/or fever during the 15 days
      preceding the study was also obtained. RESULTS: 35.8% (64/179) of the children
      presented iron deficiency and 75.4% (135/179), vitamin A deficiency. 29.1%
      (52/179) of the children presented both iron and vitamin A deficiencies. Iron
      deficiency was not associated with vitamin A deficiency. A separate analysis for
      each hematimetric index also demonstrated no significant difference between
      children with or without vitamin A deficiency. Children aged 24 to 36 months
      presented significantly higher prevalence rates of iron deficiency (p = 0.0005)
      as did children with diarrhea and/or fever during the 15 days preceding the study
      (p = 0.003). CONCLUSIONS: Although iron deficiency was not associated with
      vitamin A deficiency, high rates of both deficiencies were exhibited in a
      "healthy" population with low malnutrition indices. Such situations are known as
      "hidden hunger". Younger children presented a higher risk of iron deficiency as
      did children with diarrhea and/or fever during the 15 days preceding the study.

PMID- 15858681
TI  - [Sildenafil for pulmonary hypertension treatment after cardiac surgery].
AB  - OBJECTIVE: To report on the use of sildenafil for pulmonary hypertension
      treatment of a newborn patient after cardiac surgery. DESCRIPTION: A female, full
      term newborn infant with diagnosis of double outlet right ventricle, pulmonary
      hypoplasia and subaortic ventricular septal defect, was submitted to Blalock
      surgery in the first week of life. In postoperative the newborn had pulmonary
      hypertension and persistent hypoxia, without response to nitric oxide, but with
      improved oxygenation after continuous intravenous infusion of prostaglandin E1.
      After several failed attempts to discontinue prostaglandin E1, oral sildenafil
      was used. There was a decrease in pulmonary vascular resistance with consequent
      oxygenation improvement and 48 hours later it was possible to discontinue
      prostaglandin E1 infusion. COMMENTS: Sildenafil can be an alternative therapy for
      pulmonary hypertension, especially when there is no response to conventional
      therapy.

PMID- 15858682
TI  - [Traumatic airway disruption in a child: a diagnostic challenge].
AB  - OBJECTIVE: To report a case of airway disruption in a child victim of blunt
      thoracic trauma due to falling off a sink. DESCRIPTION: Descriptive case report.
      A 34-month old boy victim of thoracic trauma was seen at the pediatric intensive
      care unit of a university hospital. Plain chest radiograph, thoracic computed
      tomography, bronchoscopy, thoracotomy, antibiotics, hemodynamic and respiratory
      support were performed. Plain chest radiograph, thoracic computed tomography and
      bronchoscopy were performed in order to arrive at a precise diagnosis of
      traumatic airway disruption associated with pulmonary contusion, pneumothorax,
      mediastinal and subcutaneous emphysema. The patient underwent thoracotomy for
      surgical repair of an almost complete disruption of the left main bronchus.
      Antibiotics and ventilatory support contributed to a favorable outcome without
      medium-term sequelae. COMMENTS: Children presenting with thoracic trauma must be
      investigated for uncommon, but potentially lethal injuries, such as
      tracheobronchial disruption, particularly in cases where there is strong clinical
      evidence. Diagnostic workup should be optimized with plain chest radiograph and
      thoracic computed tomography, while bronchoscopy will confirm the definitive
      diagnosis.

PMID- 15858684
TI  - [Esophageal achalasia and eosinophilic esophagitis].

PMID- 15858685
TI  - [Diagnosing hepatobiliary disease in cystic fibrosis: a challenge].

PMID- 15858686
TI  - Care of the dying--whose job is it anyway?

PMID- 15858687
TI  - Johannes Evangelista Purkinje (1787-1869): 19th century's foremost
      phenomenologist.

PMID- 15858688
TI  - Symptoms and care of dying elderly patients in an acute hospital.
AB  - INTRODUCTION: We aimed to study the symptoms and the care of elderly patients
      dying in an acute hospital in Singapore. METHODS: Over a one year period, we
      retrospectively studied all patients admitted to the Department of Geriatric
      Medicine and all other patients aged more than 75 years old who were admitted and
      died during the same admission to all other units in an acute hospital. There
      were 189 such patients. Demographical data, information on the patients'
      background and prevailing medical problems, symptoms, intervention and treatment
      methods were obtained from the patients' medical records and analysed. RESULTS:
      The patients were frail and old. 17 percent had bedsores and 20 percent had limb
      contractures noted at the point of admission. 20 percent had known terminal
      disease. 88 percent of the deaths were expected and 12 percent unexpected. In
      spite of the deaths being anticipated, 25 percent of them were subjected to
      cardiopulmonary resuscitation and 17 percent were intubated at the point of
      collapse. The majority (81 percent) of relatives of the 160 patients whose deaths
      were anticipated and had family had no acceptance problems. 52 (31 percent) of
      the 167 expected deaths had input from palliative care. These patients were more
      dependent, (p-value equals 0.018; odds ratio [OR] = 2.5; 95 percent confidence
      interval [CI] 1.2-5.2), less likely to undergo resuscitation (p-value is less
      than 0.001; OR = 0.16; 95 percent CI, 0.06-0.44), and were more likely to be on
      treatment for their symptoms (p-value is equal to 0.001; OR = 7.7; 95 percent CI,
      2.1-28.8). CONCLUSION: The common symptoms experienced by the elderly at the end
      of life are difficulty with breathing, fever, pain and respiratory secretions. A
      number of patients were not on any treatment for these problems though the
      proportion is less where there is palliative input.

PMID- 15858689
TI  - Use of polymerase chain reaction on pooled cervical swabs to detect Chlamydia
      trachomatis infections in female sex workers in Singapore.
AB  - INTRODUCTION: Infections caused by Chlamydia trachomatis (C. trachomatis) is one
      of the commonest sexually transmitted infections (STI). As there is currently no
      laboratory in Singapore that offers the chlamydia culture tests, alternative
      laboratory methods were developed and antigen detection methods such as enzyme
      immunoassays (EIA) proved to be even less sensitive than cell culture. This study
      was done to assess the accuracy and sensitivity of pooling five endocervical
      swabs collected for C. trachomatis testing by polymerase chain reaction (PCR)
      technology, as compared to the currently used EIA on individual swabs, in female
      sex workers who were seen at a STI clinic in Singapore. METHODS: A total of 1,182
      endocervical swab specimens were analysed by EIA as well as in pools of five
      specimens using PCR. Any pool with a positive PCR result for C. trachomatis
      infections was subjected to repeat PCR testing of the five individual specimens
      in the pool. RESULTS: There were a total of 48 confirmed cases of C. trachomatis
      infection. EIA detected 19 positive samples for C. trachomatis, yielding a
      prevalence of 1.6 percent among the sex workers tested. Pooled PCR testing showed
      a higher prevalence rate of 4.1 percent, with 48 PCR positive samples. All cases
      that were EIA positive were also PCR positive. Individual runs on 200 random
      samples as well as on 220 individual samples from positive pooled results showed
      PCR inhibition rates ranging from 1.5 percent to 2.3 percent. However, the PCR
      inhibition rate was 0 percent with the use of pooling. Sensitivity of EIA was
      39.6 percent, with 100 percent specificity. EIA tests had a false negative rate
      of 60.4 percent. PCR was found to be 100 percent sensitive and specific.
      CONCLUSION: C. trachomatis infections among female sex workers attending the
      clinic were found to be higher using PCR technology. Less sensitive methods such
      as EIA result in undertreatment of otherwise undetected cases. The pooling
      strategy using pool sizes of five specimens, with a disease prevalence of 4.1
      percent is reliable and cost-effective, and has since been introduced in the
      current medical surveillance scheme for sex workers in the clinic.

PMID- 15858690
TI  - Characteristics and clinical predictors of minor head injury in children
      presenting to two Malaysian accident and emergency departments.
AB  - INTRODUCTION: Paediatric minor head injuries (MHI) are just as common in both
      bigger and smaller towns in Malaysia. Urban-based MHI are due more to motor
      vehicular injuries compared to rural-based MHI which are mainly due to non-motor
      vehicular injuries. The main objectives of this study were to compare incidence
      of admitted patients to accident and emergency departments of hospitals in two
      different settings in Malaysia, namely: Ipoh (urban-based) and Kota Bharu (rural
      based); and to correlate to demographical characteristics, types of accident,
      clinical signs and symptoms, radiological and computed tomography (CT) findings,
      management; and finally, to determine clinical predictors of intracranial injury
      in MHI. METHODS: A cross-sectional study of 153 paediatric patients aged 2-18
      years who were admitted to the Ipoh Hospital, Perak and 112 patients of the same
      age group admitted to Hospital Universiti Sains Malaysia, Kelantan were included
      in this study. The study period was between 1 January 1998 and 31 December 2001.
      Data collection was done prospectively. Chi-square and independent t-tests were
      applied to compare characteristics of patients admitted to these two hospitals.
      Backward stepwise multiple logistic regression was applied to determine clinical
      predictors of intracranial injury. RESULTS: There were significant differences of
      age, race, types of accidents, clinical signs and symptoms, Glasgow coma scale
      (GCS), skull fracture and CT findings between two hospitals. Significant clinical
      predictors were headache (OR 20.8, 95 percent CI 3.9-25.2, p-value is less than
      0.001), unequal pupils (OR 8.4, 95 percent CI 4.3-17.9, p-value is equal to
      0.0413) and GCS score of 13 (OR =3.8, 95 percent CI 1.9-6.8, p-value is equal to
      0.005). Skull fractures and intracranial injuries were more common in Kota Bharu
      due to children riding motorcycles without helmets than in Ipoh (p-value is less
      than 0.001). CONCLUSION: In the rural Malaysian community, both the police and
      physicians must be alerted to the fact that unhelmeted children riding
      motorcycles are more likely to sustain morbidity than those in urban areas. More
      aggressive traffic policing of the village roads should be done by the relevant
      authorities.

PMID- 15858691
TI  - Rapid diagnosis of Helicobacter pylori infection in dyspeptic patients using
      salivary secretion: a non-invasive approach.
AB  - INTRODUCTION: Current guidelines that recommend Helicobacter pylori eradication
      treatment without endoscopy in selected patients underscore the importance of non
      invasive testing. The accuracy of saliva as a non-invasive specimen was compared
      with that of invasive tests in pretreatment diagnosis of H. pylori infection.
      METHODS: One hundred patients undergoing gastroscopy were grouped into 80
      symptomatic and 20 asymptomatic subjects and were investigated for the presence
      of H. pylori in saliva and stomach. Samples tested comprised saliva and gastric
      biopsies collected from each patient. Exclusion criteria were history of peptic
      ulcer, bleeding ulcer, cancer or recent use of antibiotics, proton pump
      inhibitors and non-steroidal anti-inflammatory drugs. Two sets of primers
      homologous to 534 bp fragment of H. pylori DNA, which have been shown previously
      to be highly specific and sensitive, were used for the polymerase chain reaction
      (PCR) amplification. RESULTS: 72 (90 percent) of the symptomatic group and 10
      asymptomatic subjects were infected with H. pylori in the stomach as determined
      by histology and direct PCR amplification of biopsy DNA obtained from each
      subject. H. pylori DNA was identified in the saliva of 70 (87.5 percent)
      symptomatic subjects and 12 (60 percent) asymptomatic control subjects.
      CONCLUSION: High rates of detection using saliva as a specimen indicate that
      saliva of the infected person could serve as a reliable non-invasive alternative
      to detect the presence of H. pylori infection in comparison to the currently
      available standard diagnostic tests.

PMID- 15858692
TI  - Kikuchi's disease: a Singapore case series.
AB  - INTRODUCTION: Kikuchi's disease is a benign form of cervical lymphadenopathy that
      commonly affects young adults. We report a case series from our hospital.
      METHODS: The clinical features of 23 cases of Kikuchi's disease diagnosed at
      Changi General Hospital over a seven year period are presented. The cases were
      identified from pathology records using the search term histiocytic necrotising
      lymphadenitis. RESULTS: Most of our patients (78 percent) were young women who
      presented with cervical lymphadenopathy. The median age was 31 years. In the 18
      cases who completed follow-up at the hospital, there was spontaneous resolution
      of symptoms within a six-month period. One patient demonstrated seropositivity
      for systemic lupus erythematosus (SLE) and was initially started on steroids.
      However, the treatment was discontinued shortly afterwards since she did not meet
      the diagnostic criteria for SLE. Excision biopsy of the affected lymph node was
      the diagnostic method of choice. CONCLUSION: Kikuchi's disease is not uncommon in
      the Singaporean population. Establishing an early diagnosis is crucial since the
      clinical presentation can mimic tuberculous lymphadenitis or malignant lymphoma.
      The diagnostic method of choice is excision biopsy.

PMID- 15858693
TI  - Musculoskeletal melioidosis masquerading as diabetic amyotrophy.
AB  - A patient with musculoskeletal melioidosis masquerading as diabetic amyotrophy is
      described. A 43-year-old man presented with left thigh pain, fever, malaise and
      loss of weight. He had diabetes mellitus for six years. He was initially
      diagnosed with diabetic amyotrophy and was treated conservatively. Recurrence of
      symptoms prompted further investigations which revealed melioidosis of the left
      femur. Magnetic resonance imaging showed an enhancing subperiosteal collection.
      The diagnosis was confirmed by open biopsy and tissue culture. Acute treatment
      consisted of intravenous ceftazidime for 24 days and oral cotrimoxazole. The
      patient showed marked improvement clinically and biochemically. He was discharged
      with oral doxycycline and cotrimoxazole for three months. This disease is
      eminently treatable, but can be a diagnostic challenge when it presents in an
      uncommon site.

PMID- 15858694
TI  - Hyperglycaemia as an indicator of concurrent acute pancreatitis in fulminant
      hepatic failure associated with hepatitis B infection.
AB  - Pancreatitis occurring concurrently with fulminant hepatic failure (FHF) is
      primarily detected on autopsy and is seldom clinically apparent. We report a
      fatal case of FHF in a 25-year-old woman which was related to acute hepatitis B
      infection. In this patient, hyperglycaemia needing insulin infusions led to the
      detection of acute pancreatitis. FHF complicated by acute pancreatitis has a poor
      prognosis. A high index of suspicion is necessary for its diagnosis. The role of
      orthotopic liver transplantation and use of antiviral therapies need further
      evaluation in this situation.

PMID- 15858695
TI  - Clinics in diagnostic imaging (103). Dural sinus thrombosis with cerebral venous
      infarction.
AB  - A 13-year-old boy had a history of severe headache for two weeks. He also had
      seizures and vomited many times. Neurological examination was normal except for
      bilateral papilloedema. Sagittal T1-weighted magnetic resonance (MR) images
      showed loss of the normal flow void in the superior sagittal sinus. There was
      hyperintensity, which came from subacute thrombosis in the posterior half of the
      superior sagittal sinus. MR venography confirmed loss of flow signal in the
      superior sagittal sinus. There was also thrombosis of the right transverse, right
      sigmoid, and left transverse sinuses, and haemorrhagic infarctions in the right
      frontal and left parietal regions. A diagnosis of dural sinus thrombosis with
      cerebral venous infarction was made. CT, MR imaging, MR venography, and CT
      venography findings are discussed in patients with cerebral venous thrombosis.

PMID- 15858696
TI  - Electrocardiographical case. A case of wide complex tachycardia.
AB  - A 43-year-old Chinese woman complained of a one week history of irregular rapid
      palpitations associated with chest discomfort and dyspnoea. Her heart rate was
      more than 160 beats per minute and blood pressure was 154/95 mmHg. 12-lead
      electrocardiogram (ECG) showed a wide complex tachycardia with a slightly
      irregular rhythm. Delta waves were also present. She was treated appropriately
      with intravenous procainamide but developed torsades de pointes secondary to
      prolonged QT interval. Electrophysiology study revealed atrial tachycardia with a
      left-sided accessory pathway which was successfully ablated.

PMID- 15858697
TI  - Periampullary diverticulum causing biliary stricture and obstruction.

PMID- 15858701
TI  - [The "quality house pediatric oncology" as an instrument for improving the
      performance of the trial centers].
AB  - The project group "Central Trial Support" of the German Competence Network
      Pediatric Oncology and Haematology supports the members of the Society of
      Pediatric Oncology and Haematology in their effort to cope with the growing
      statutory, ethical and administrative requirements for therapy optimization
      studies (investigator-initiated, non-profit clinical trials). By these quality
      improvement measures the studies will become more revisable and reliable, but at
      the same time their processing will become more and more complex. The basic
      instrument of the project group "Central Trial Support" will be the so-called
      "Quality House" which has been built up in order to improve the performance of
      the associated study centres and to help put a systematic quality management
      system into practice. The "Quality House Pediatric Oncology" comprises detailed
      descriptions of the activities of all trial center co-workers. Its process map
      details all operational sequences which constitute an efficiently performing
      trial center. The so-called value adding processes are explained step by step,
      and the associated specific tasks are assigned to each respective co-worker. At
      each process step, the person in charge will have explanatory descriptions at
      her/his disposal and - if necessary - further problem solving means as well as
      references to possible optimization measures (e. g. Standard Operating Procedures
      and other documents). The German Competence Network Pediatric Oncology and
      Haematology will be implementing this electronic quality management system in
      trial centers which will convince both sponsors and authorities of the compliance
      with requirements and standards.

PMID- 15858702
TI  - Intensification of chelating-therapy in patients with thalassemia major.
AB  - With the introduction of "hypertransfusion" regimens the extent of disease- and
      therapy-related hemosiderosis has become the survival limiting factor for
      patients with beta-thalassemia major as iron transferred with transfusions cannot
      be excreted by physiological means. Subsequent introduction of deferoxamine
      therapy for iron elimination and prophylaxis of hemosiderosis has improved
      prognosis and life quality of these patients considerably. We report our
      experience with seven adolescent patients with beta-thalassemia and ineffective
      subcutaneous therapy and severe hemosiderosis-related organ complications. For
      that reason they received i. v. intensified chelate therapy. The patients were
      given 70 to 120 mg/kg DFO 7 days a week continuously via a Port-a-cath or Hickman
      central venous line. Under high-dose i. v. DFO therapy, serum ferritin levels
      significantly decreased in all patients. Target serum ferritin levels of 3 000
      ng/ml were reached after 12 to 20 months of treatment. In 3 of the 5 patients
      that were treated for longer than 43 months serum ferritin levels even dropped
      below 2 000 ng/ml. Serum ferritin levels also correlated well with SQUID
      examinations. Therefore, monitoring of serum ferritin may be useful to monitor
      patient's compliance and control intensified DFO therapy. Continuous
      administration of the intensified DFO therapy induced normalization of liver
      function and left ventricular cardiac function in all patients who are still
      alive. Two patients died due to cardiac decompensation. In five patients 19
      episodes of central catheter-related infections were observed (1.5 infections per
      1 000 catheter days). No DFO-associated allergic reactions nor irreversible organ
      dysfunction were observed. Our results indicate that intensified i. v. DFO
      therapy is an effective and safe method for treatment of severe organ dysfunction
      in patients with thalassemia major. The most severe problems are catheter-related
      infections and inconsistent long-term compliance.

PMID- 15858703
TI  - Immunophenotype of Down syndrome acute myeloid leukemia and transient
      myeloproliferative disease differs significantly from other diseases with
      morphologically identical or similar blasts.
AB  - BACKGROUND AND OBJECTIVES: Children with Down Syndrome (DS) have a 20-40 fold
      increased risk of developing acute myeloid leukemia (AML), mainly of the
      megakaryoblastic subtype (AMKL). Approximately 10 % of newborns with DS show
      transient myeloproliferative disease (TMD) which normally resolves spontaneously.
      The blast cells of both entities show megakaryoblastic/erythroblastic features
      (M7/M6) and cannot be distinguished by morphological characteristics. DESIGN AND
      METHODS: Blast cells of 62 children were analyzed by four-color flow cytometry
      and dual color fluorescence microscopy. RESULTS: The immunophenotype of blast
      cells from children with TMD and DS-AMKL is characterized by the expression of
      CD33 (+)/CD13 (+/-)/CD38 (+)/CD117 (+)/CD34 (+/-)/CD7 (+)/CD56 (+/-)/CD36
      (+)/CD71 (+)/CD42b (+)/CD4dim (+)/TPO-R (+)/EPO-R (-)/IL-3-Ralpha (+)/IL-6-Ralpha
      (-). Non-DS children with morphologically related diseases, i. e. myelodysplastic
      syndrome (MDS), juvenile myelomonocytic leukemia (JMML), or AML-M6 and AML-M7,
      did not show this expression profile. CD34 expression was observed in 93 % of
      TMD, but only 50 % of DS-AMKL patients. The blast cells of all TMD and DS-AMKL
      cases were positive for TPO-R and IL-3R, whereas EPO-R and IL-6R were absent.
      CONCLUSIONS: Immunophenotyping by the use of surface antigens and growth factor
      receptors is a useful tool to discriminate TMD and DS-AMKL from diseases with
      morphologically similar or identical blasts. The absence of EPO-R on the blast
      cells might be a sign of the high expression of the mutated -- and less active --
      GATA1 in DS. The higher amount of CD34 co-expression in TMD may be interpreted to
      indicate that TMD is a slightly more immature disease than DS-AMKL.

PMID- 15858704
TI  - Similar survival following HLA-identical sibling transplantation for standard
      indication in children with haematologic malignancies: a single center comparison
      of mobilized peripheral blood stem cell with bone marrow transplantation.
AB  - BACKGROUND: Peripheral blood stem cell (PBSC) grafts are increasingly used for
      autologous and allogeneic haematopoietic stem cell transplantation (alloHSCT)
      with the aim to hasten neutrophil and platelet engraftment and thereby to reduce
      transplant-related complications due to infections, bleeding and graft failure.
      Based on the paucity of data on PBSC transplantation in children we performed a
      retrospective single-center analysis comparing the outcome of children receiving
      mobilized PBSC from human leukocyte antigen (HLA)-identical sibling donors to
      bone marrow (BM) transplant recipients. PATIENTS AND METHODS: Between 1996 and
      2004, 16 children with haematologic malignancies and standard indication for
      alloHSCT underwent PBSC transplantation from HLA-identical sibling donors. The
      outcome of these children was compared to a historic control group of 19 bone
      marrow (BM) transplant recipients. Time to neutrophil engraftment, incidence of
      acute and chronic graft-versus-host disease (GvHD), relapse rate, transplant
      related mortality, event-free and overall survival were analyzed. RESULTS:
      Neutrophil engraftment was achieved significantly faster after PBSC compared to
      BM transplantation with a median time to neutrophil engraftment of 11 (range: 8
      21) and 19 (16-44) days for the PBSC and BM cohort, respectively (p < 0.001). Two
      of 19 (11 %) BM recipients did not achieve primary neutrophil engraftment and
      both patients died due to infectious complications. The rate of clinically
      significant acute GvHD > or = grade II was higher in the PBSC compared to the BM
      group (75 vs. 39 %; p = 0.045). Incidences of chronic GvHD (PBSC vs. BM: 60 vs.
      44 %), death of disease (13 vs. 21 %) and death of complication (13 vs. 16 %)
      were comparable between both groups (p = ns). With a median follow up of 4.7
      years (PBSC) and 10.2 years (BM) overall survival (PBSC vs. BM: 68.6 +/- 13.5 vs.
      63.2 +/- 11.1 %; p = 0.65) and event-free survival (67.0 +/- 12.1 vs. 63.2 +/-
      11.1 %; p = 0.80) is without demonstrable difference in both groups. CONCLUSIONS:
      Transplantation of PBSC compared to BM is associated with faster neutrophil
      engraftment and a higher rate of > or = grade II acute GvHD. As overall survival
      and event-free survival is similar when using PBSC and BM, PBSC is an alternative
      stem cell source for HLA-identical sibling transplantation. Further prospective
      analyses with higher number of patients stratified according to well established
      risk factors are required to define the precise role of both stem cell sources
      for children with haematologic malignancies.

PMID- 15858705
TI  - [Lectin-reactive alpha-fetoprotein in tyrosinaemia type I].
AB  - Despite the introduction of NTBC into the treatment of tyrosinaemia type I (TT1)
      and a considerable improvement in the outcome of these patients, the principal
      risk of developing hepatocellular carcinoma (HCC) in this metabolic disorder
      remains mainly in those children with late introduction of NBTC after the second
      year of life. Serial total alpha-Fetoprotein (AFP) levels are used to evaluate
      the individual risk to develop malignant changes. A failure of AFP to decrease on
      adaequate treatment or a secondary increase after a period of falling levels have
      been an indication for liver transplantation. Lectin-reactive alpha-Fetoprotein
      is a recently described marker to distinguish hepatocellular carcinoma from
      benign liver disease in adult cirrhotic patients. AIMS: To investigate if the
      analysis for Lectin-reactive alpha-Fetoprotein would lead to earlier detection of
      HCC compared to a judgement based on the evolution of standard total AFP alone.
      PATIENTS: We report the analysis of 12 patients with TTI and histologically
      proven HCC. There of 5 were diagnosed under one year of age, but NTBC treatment
      was started between 2 years 3 month and 7 years of age except in one case in
      which NTBC was introduced when the diagnosis of TTI was made. The remainder of
      the patients cover up to the age of 15 years. All patients had been treated with
      NTBC. METHODS: Lectin containing agarose gel for AFP electrophoresis leads to AFP
      separation according to different affinities of the varying carbohydrate chains
      of AFP to lectins. RESULTS: AFP subfractions could be identified in all 12
      patients. In 6 patients the L3-AFP rose before the total AFP. In 3 patients the
      rise in L3-AFP was consistent with the rise of the total AFP and in 3 patients
      the L3-AFP was raised after the total AFP or did not increase at all. DISCUSSION:
      We were able to identify 6 out of 12 patients who had an early increase of L3-AFP
      before they developed a change in total AFP levels. The clinical significance of
      these early changes need to be determined. Lectin-affinity electrophoresis may
      have a potential role as an additional tool that may help to discriminate benign
      liver disease from HCC in TTI. CONCLUSIONS: We suggest the further evaluation of
      lectin-reactive AFP in TTI.

PMID- 15858706
TI  - Infants with stage 4 neuroblastoma: the impact of the chimeric anti-GD2-antibody
      ch14.18 consolidation therapy.
AB  - BACKGROUND: Antibody treatment is considered tolerable and potentially effective
      in the therapy of neuroblastoma. We have analyzed the clinical data of infants <
      1 year with stage 4 neuroblastoma with regard to the consolidation treatment.
      PATIENTS AND METHODS: Infants < 1 year with stage 4 neuroblastoma who completed
      initial treatment (6-8 chemotherapy cycles followed either by 4 cycles low dose
      oral chemotherapy or high dose chemotherapy with stem cell transplantation)
      without event were eligible for this trial. Consolidation therapy consisted of 6
      cycles of antibody ch14.18 (20 mg/m(2) x d ch14.18 for 5 days every 2 months) or
      12 months oral maintenance chemotherapy (MT). RESULTS: Of 59 evaluable patients,
      31 received a total of 159 ch14.18 cycles, 16 received MT instead, and 12 had no
      further treatment. Fever (47 % of cycles), abnormal CRP without infection (25 %),
      rash (23 %), cough (16 %), and pain (8 %) were the main side effects. Univariate
      analysis found no difference in event free survival (3-year-EFS 80.5 +/- 7.1 %,
      87.5 +/- 8.3 %, and 75.0 +/- 12.5 % for patients treated with antibody ch14.18,
      MT, and no further therapy, p = 0.433) and overall survival (3-year-OS 90.1 +/-
      5.4 %, 93.8 +/- 6.0 %, and 91.7 +/- 8.0 % for patients treated with antibody
      ch14.18, MT, and no further therapy, p = 0.931). Multivariate analysis failed to
      demonstrate an advantage of antibody treatment. CONCLUSION: The outcome of
      infants with stage 4 neuroblastoma is good. Consolidation treatment with ch14.18
      was tolerable but associated with fever, elevated CRP, rash, cough, and pain as
      side effects. Compared to oral maintenance chemotherapy and no consolidation
      treatment, ch14.18 treatment had no impact on the patients' outcome which
      confirms the results found in children > 1 year.

PMID- 15858707
TI  - [Supratentorial primitive neuroectodermal tumor: a single center experience and
      comparison with the literature].
AB  - Supratentorial primitive neuroectodermal tumors (stPNETs) are malignant tumors.
      We saw within three years six children with stPNETs. In four of the six children
      radical resection could be achieved. All had craniospinal irradiation and
      chemotherapy according to the HIT-91 protocol. The two children with incomplete
      resection died due to tumor progression after 7 and 10 months. Two of the 4
      children with complete tumor resection had local relapses 8 months after
      diagnosis and died after 14 and 18 months. One child had a diffuse meningeal
      relapse 12 months after diagnosis. Despite (high-dose) systemic chemotherapy and
      intraventricular mafosfamide, he died 21 months after diagnosis due to tumor
      although remission could be achieved. Only one child is still in remission 86
      months after diagnosis.

PMID- 15858708
TI  - New antifungal drugs and the pediatric cancer patient: current status of clinical
      development.
AB  - Invasive mycoses are important causes for treatment related morbidity and
      mortality in severely immunocompromised pediatric patients with hematological
      malignancies or hematopoietic stem cell transplantation. The past decade has
      witnessed a major expansion of antifungal drug research, which has resulted in
      the development of the novel class of echinocandin lipopeptides (anidulafungin,
      micafungin, caspofungin) and a new generation of antifungal triazoles with
      improved pharmacological properties (posaconazole, ravuconazole, voriconazole).
      Whereas caspofungin and voriconazole have been licensed in the European Union,
      the United States, Canada and several other countries throughout the world,
      posaconazole, ravuconazole, anidulafungin and micafungin are under regulatory
      review or in advanced stages of clinical development. Caspofungin and
      voriconazole are increasingly prescribed in pediatric patients, although
      pediatric dosage finding and safety evaluations have not been completed. This
      article reviews the clinical pharmacology of the new antifungal agents and the
      status of their clinical development in immunocompromised pediatric patients.

PMID- 15858709
TI  - [Follow up of long-term survivors after childhood cancer in Germany].
AB  - BACKGROUND: In recent years, the long-term survival of childhood cancer patients
      has increased considerably. While this is desirable, more patients with late
      effects are to be expected and studies thereof become increasingly important. We
      will need to be able to stay in touch with as many former patients as possible in
      order to make a systematic and comprehensive long-term follow-up possible.
      PATIENTS: Childhood cancer patients under 15 years of age at diagnosis resident
      in Germany and registered at the German Childhood Cancer Registry (GCCR).
      METHODS: The GCCR has established a 3-phase procedure for follow-up. We developed
      principles for the long-term follow up of these patients. They are based on the
      many years of experience at the GCCR and were developed based on the long
      standing collaboration between the therapy optimization studies (TOS) in the
      Society for Paediatric Oncology and Haematology (GPOH) and the GCCR. RESULTS:
      Currently 8 012 adult survivors diagnosed before 2000 are under observation at
      the GCCR and could be contacted for studies. About half of the children diagnosed
      in the 1980ies still in follow-up have been under observation more than 14 years.
      When asked to personally extend the originally parental consent to data storage
      at the GCCR and the TOS at about 16 years of age, about 85 % of the patients
      agree. CONCLUSIONS: Establishing an open-end, systematic long-term follow-up will
      provide a unique and broad basis for paediatric oncology in Germany to perform
      representative studies regarding long-term survival after childhood cancer in
      Germany in the long run.

PMID- 15858710
TI  - Prospective multicenter registration of major late sequelae in sarcoma patients
      using the Late Effects Surveillance System (LESS).
AB  - BACKGROUND: Late effects become progressively more important for the evaluation
      of therapeutic success in paediatric oncology. Thus, in 1998, the Late Effects
      Surveillance System (LESS) started to register and assess multicentrally,
      prospectively and longitudinally late effects of treatment for the group of
      Ewing's, soft tissue- and osteosarcoma patients. PATIENTS AND METHODS: The yearly
      results of the follow-up examinations of 785 Ewing's, soft tissue- and
      osteosarcoma patients, who were treated from 1.1.1998 until 31.12.2001, were
      prompted and assessed conforming to the guidelines developed by the LESS-study.
      RESULTS: 136/181 (75 %) of follow-up institutions take part in the LESS-study.
      Only 8 % of patients eligible for the LESS-study were cared for in non
      cooperating facilities. Questionnaire return could be raised to 73-78 % and data
      completeness could also be significantly improved in the course of the study.
      Departments of internal medicine had a lower questionnaire return percentage than
      departments of paediatrics. Data availability for the nephrologic after-care was
      not satisfactory. CONCLUSIONS: The LESS project has been well established. Thus,
      the basis has been set for the development of risk-oriented strategies for
      intervention and for the further improvement of the follow-up of major late
      effects in sarcoma patients.

PMID- 15858712
TI  - Forum on economic credentialing (E.C.).

PMID- 15858713
TI  - Antibiotic update for the surgeon.

PMID- 15858711
TI  - Alternative splicing suggests extended function of PEX26 in peroxisome
      biogenesis.
AB  - Matsumoto and colleagues recently identified PEX26 as the gene responsible for
      complementation group 8 of the peroxisome biogenesis disorders and showed that it
      encodes an integral peroxisomal membrane protein with a single C-terminal
      transmembrane domain and a cytosolic N-terminus that interacts with the PEX1/PEX6
      heterodimer through direct binding to the latter. They proposed that PEX26
      functions as the peroxisomal docking factor for the PEX1/PEX6 heterodimer. Here,
      we identify new PEX26 disease alleles, localize the PEX6-binding domain to the N
      terminal half of the protein (aa 29-174), and show that, at the cellular level,
      PEX26 deficiency impairs peroxisomal import of both PTS1- and PTS2-targeted
      matrix proteins. Also, we find that PEX26 undergoes alternative splicing to
      produce several splice forms--including one, PEX26- delta ex5, that maintains
      frame and encodes an isoform lacking the transmembrane domain of full-length
      PEX26 (PEX26-FL). Despite its cytosolic location, PEX26- delta ex5 rescues
      peroxisome biogenesis in PEX26-deficient cells as efficiently as does PEX26-FL.
      To test our observation that a peroxisomal location is not required for PEX26
      function, we made a chimeric protein (PEX26-Mito) with PEX26 as its N-terminus
      and the targeting segment of a mitochondrial outer membrane protein (OMP25) at
      its C-terminus. We found PEX26-Mito localized to the mitochondria and directed
      all detectable PEX6 and a fraction of PEX1 to this extraperoxisomal location; yet
      PEX26-Mito retains the full ability to rescue peroxisome biogenesis in PEX26
      deficient cells. On the basis of these observations, we suggest that a
      peroxisomal localization of PEX26 and PEX6 is not required for their function and
      that the interaction of PEX6 with PEX1 is dynamic. This model predicts that, once
      activated in an extraperoxisomal location, PEX1 moves to the peroxisome and
      completes the function of the PEX1/6 heterodimer.

PMID- 15858714
TI  - Surgical imaging systems.

PMID- 15858715
TI  - 3-D ultrasound for the evaluation of malignant disease.

PMID- 15858716
TI  - Could intraoperative analgesia attenuate excessive neuroendocrine responses in
      surgical patients?

PMID- 15858717
TI  - Technology assessment.

PMID- 15858718
TI  - The role of outcomes research in improving the quality of medical care.

PMID- 15858719
TI  - Transfusion medicine and surgery.

PMID- 15858720
TI  - Biocompatible electric current attenuates HIV infectivity.

PMID- 15858721
TI  - Dynamic optical imaging.

PMID- 15858722
TI  - Open mesh plug hernioplasty: the less invasive procedure.

PMID- 15858724
TI  - Laparoscopic intraoperative ultrasonography.

PMID- 15858723
TI  - Laparoscopic r/evolution: impetus to a new understanding of surgery.

PMID- 15858725
TI  - Economic considerations in laparoscopic surgery: disposable versus reusable
      instrumentation.

PMID- 15858726
TI  - Initial experience of 3-D video endoscopy in general surgery.

PMID- 15858727
TI  - Entry technique for laparoscopy.

PMID- 15858728
TI  - An ambulatory bilirubin monitoring device for duodenogastroesophageal reflux.

PMID- 15858729
TI  - Clinical application of three-dimensional (3-D) vision systems and virtual
      reality helmets in video-assisted surgery.

PMID- 15858730
TI  - Laparoscopic removal of posterior gastric wall polyp trough gastrotomy using hand
      suturing and mechanical abdominal wall retractor.

PMID- 15858732
TI  - Visually guided trocar entry: experience with the optical trocar.

PMID- 15858731
TI  - Laparoscopic adjustable silicone gastric banding (LASGB) for the treatment of
      morbid obesitiy.

PMID- 15858733
TI  - Laparoscopic gastrotomy in intragastric surgery for early gastric cancer: a new
      technique.

PMID- 15858734
TI  - Technique of transanal endoscopic microsurgery (TEM).

PMID- 15858735
TI  - Laparoscopic removal of a mesenteric cyst together with the calculous
      gallbladder: a case report.

PMID- 15858737
TI  - Tissue morcellation in endoscopic surgery.

PMID- 15858736
TI  - Jaundice secondary to spilled gallstone during laparoscopic cholecystectomy.

PMID- 15858738
TI  - The effect of various ovulation induction protocols on pregnancy rates following
      intracytoplasmic sperm injection.

PMID- 15858739
TI  - Laparoscopic ovarian cystectomy: extraperitoneal method.

PMID- 15858740
TI  - Abdominal wall stability: a comparison of the optical trocar with a reusable
      laparoscopic trocar.

PMID- 15858741
TI  - Laparoscopic nephrectomy: present state and future developments.

PMID- 15858742
TI  - Laser irradiation for the treatment of benign prostatic hyperplasia.

PMID- 15858743
TI  - The clinical anatomy of undescended testis and varicocele for laparoscopic
      management.

PMID- 15858744
TI  - Mycophenolate mofetil: clinical update.

PMID- 15858745
TI  - Orthotopic liver transplantation in U.S. veterans under primary tacrolimus
      immunosupression.

PMID- 15858746
TI  - Regulation of the anti-allograft response by targeting the CD2 antigen: a
      potential strategy for the creation of transplant tolerance.

PMID- 15858747
TI  - Hyperthermic intraoperative intreperitoneal chemotherapy (HIIC) with mitomycin C.

PMID- 15858748
TI  - The evolution of minimally invasive breast biopsy: from FNA to percutaneous
      incisional and excisional biopsy.

PMID- 15858749
TI  - Surgical applications of gamma-detecting probes.

PMID- 15858751
TI  - Etiology of aortic aneurysm.

PMID- 15858750
TI  - How reliable are conventional and color-coded sonography of the breast in the
      differential diagnosis of breast cancer?

PMID- 15858752
TI  - Transcriptional regulation of endothelin.

PMID- 15858753
TI  - Intracoronary stents.

PMID- 15858754
TI  - Endovascular aortic devices: the Parodi and Palmaz system.

PMID- 15858755
TI  - Optimal imaging for endovascular procedures: redefining the gold standard.

PMID- 15858756
TI  - Spinal cord protection with distal perfusion for thoracic and thoracoabdominal
      aortic surgery.

PMID- 15858757
TI  - Minimal and direct access aortoiliac reconstructive surgery.

PMID- 15858758
TI  - Minimally invasive neurosurgery.

PMID- 15858760
TI  - Current concepts in mandibular reconstruction by microsurgical free flaps.

PMID- 15858759
TI  - Neuroendoscopy.

PMID- 15858761
TI  - The aging eye: pathophysiology and management.

PMID- 15858762
TI  - Current concepts in intramedullary nailing.

PMID- 15858763
TI  - Total hip replacement: the current perspective after 37 years.

PMID- 15858764
TI  - A new surgical technique for carpal instability with scapholunate dissociation.

PMID- 15858765
TI  - Diagnosis and treatment of deep vein thrombosis.

PMID- 15858766
TI  - Deep vein thrombosis following posterior lumbar spinal surgery.

PMID- 15858767
TI  - Evaluation of cold therapy in postoperative spine patients.

PMID- 15858768
TI  - Effect of snuff on nasal mucosa.
AB  - PURPOSE: The inhalation of nasal snuff (powdered tobacco) is a common addiction
      in the Indian subcontinent. In the western world, there is a resurgence of
      interest in nasal snuff because it does have the morbidity associated with smoked
      tobacco. Very few studies have reported the long-term effects of snuff on nasal
      mucosa. The objective of the present study was to investigate the effect of long
      term use of snuff on the nasal mucosa. MATERIALS AND METHODS: We conducted a
      retrospective study on 29 snuff users. We investigated the reasons for initiation
      of this particular form of addiction along with the clinical signs and symptoms
      of long-term snuff usage. At the time of the study, all patients complained of
      one or more nasal symptoms. Nasal obstruction and nasal discharge taken together
      were reported by 62.5% of patients. Gross mucosal edema of the septum and
      turbinates was the main finding on nasal examination. The absolute eosinophil
      count and total serum immunoglobulin E were elevated in 62.5% and 66.7% of
      patients, respectively. On skin prick test, 41% of patients reacted positively to
      snuff and 25% to tobacco. Histopathologic examination of the turbinates (16
      patients) showed squamous metaplasia, capillary proliferation, capillary and
      venous dilatation, inflammatory cell reaction, subepithelial edema, and fibrosis.
      CONCLUSIONS: Much has been written about the advantages of nasal snuff over
      products that deliver tobacco smoke. Our study shows that snuff users, after long
      term abuse, develop a form of chronic rhinitis, as a consequence of which they
      develop blocked and stuffy noses. We conclude that nasal snuff is not a suitable
      substitute for smoked tobacco because it does not avoid ill health.

PMID- 15858769
TI  - Injection of botulinum toxin A for the treatment of dysfunction of the upper
      esophageal sphincter.
AB  - OBJECTIVE: The objective was to evaluate changes in swallow safety and dietary
      status after the transcutaneous injection of botulinum toxin A into the upper
      esophageal sphincter in a series of outpatients with dysphagia. STUDY DESIGN:
      This was an experimental, prospective, nonrandomized study. METHODS: Patients who
      were at risk for aspiration and who had an unsuccessful trial of swallowing
      therapy were admitted to the study. All patients showed significant pooling of
      fluids in the postcricoid region. All patients were treated in the office; none
      had previous esophageal dilatation. The upper border of the cricoid cartilage was
      identified using standard electromyogram procedures and 100 U of botulinum toxin
      (Botox A) were injected. Outcomes were assessed using the penetration-aspiration
      scale, patients' short-term and long-term subjective impressions of their ability
      to swallow, and change in dietary status. RESULTS: Thirteen patients underwent an
      instrumental evaluation of swallowing function at approximately 6 months after
      treatment to corroborate the self-reported changes in swallowing. Of the 13
      patients, 12 showed an overall improvement in their ability to take an oral diet
      safely as evidenced by the penetration-aspiration scale. Of the 12 patients who
      were on a non-oral or nearly non-oral diet, 9 resumed a normal oral diet. The
      remaining 3 were on an oral diet supplemented by percutaneous endoscopic
      gastrostomy feeding. One patient remained on a non-oral diet. CONCLUSIONS:
      Injection of Botox A in the office with no additional treatments resulted in a
      long-term increase in swallow safety, a reduction of penetration and/or
      aspiration, and a reduced need for non-oral feeding. Injection of Botox A in the
      office should be considered when there is failure of the cricopharyngeus muscle
      to relax after the swallow, significant pooling in the cricopharyngeal region,
      and a risk for penetration and aspiration.

PMID- 15858770
TI  - Dynamic contrast-enhanced magnetic resonance imaging in radiotherapeutic efficacy
      in the head and neck tumors.
AB  - PURPOSE: The purpose to this study is to identify correlations between pathology
      and dynamic contrast-enhanced magnetic resonance imaging (MRI) and to assess the
      utility of this technique in the evaluation of radiation response for head and
      neck cancer. MATERIALS AND METHODS: MRI was prospectively performed after
      radiotherapy in 27 patients with various head and neck tumors. After bolus
      injection of contrast material, a dynamic study was performed using a spoiled
      gradient-recalled imaging sequence. The maximum slope of increase (MSI) on the
      time-intensity curve was displayed as a color-coded image. The ratio of MSI
      (MSIR) was obtained for tumor and normal muscles. Pathological specimens were
      obtained after MRI in all cases. Histological grading of irradiation changes was
      classified into 5 grades (0-4). Correlations between MSIR and histological grade
      were examined. RESULTS: Histologically, 18 tumors were classified as grade 2
      (presence of viable tumor cells), 4 were grade 3 (nonviable tumor cells), and 5
      were grade 4 (no tumor cells). Although the mean +/- SD of MSIR in patients with
      histological grade 2 or 3 was 7.4 +/- 7.9, MSIR in patients with grade 4 was 1.8
      +/- 0.73, representing a significant difference ( P < .05). Every patient with
      grade 4 displayed an MSIR of 2.5 or less, although 5 of 22 patients with grade 2
      or 3 had an MSIR of 2.5 or less. CONCLUSIONS: MSI quantitatively reflects
      response to radiotherapy for head and neck cancer. Color-coded MSI display is
      feasible for depicting permeability changes after radiotherapy.

PMID- 15858771
TI  - Anastomoses between the cervical branch of the facial nerve and the transverse
      cervical cutaneous nerve.
AB  - Head and neck surgeons must possess a thorough knowledge of facial nerve anatomy
      to avoid inducing iatrogenic injury during surgery. Anastomoses of the cervical
      branch (CB) of the facial nerve and the transverse cervical cutaneous nerve
      (TCCN) are poorly documented in our field. Knowledge of these anastomoses and
      their positions allows for (1) preservation of high CBs that contribute to lower
      lip depressor function, and (2) identification of the facial nerve in retrograde
      dissections. Our objective was to improve understanding of facial nerve anatomy
      by describing these anastomoses. The communicating branch between the TCCN and
      the CB was evaluated in 22 adult neck halves (11 cadavers). The facial nerve was
      exposed, and the CB was traced anteriorly. The TCCN was identified and traced
      superiorly to its anastomosis(es) with the CB. The distance from each anastomosis
      to the selected landmarks was recorded. Between the CB and the TCCN, 33
      anastomoses were identified, with at least 1 anastomosis per hemineck and 2
      anastomoses in 11 heminecks. Anastomoses were identified along the inferior
      border of the submandibular gland (SMG; 20 specimens) or posterior to the SMG (12
      specimens). Five specimens had both anastomoses near the inferior border of the
      SMG, and 6 specimens had 1 anastomosis near the inferior border and 1 posterior
      to the SMG. Communication between the TCCN and the CB is regularly present. Its
      anatomic locations are either posterior to the SMG, often within the parenchyma
      of the parotid gland, or near the inferior border of the SMG. Awareness of these
      anastomoses allows a method for identification and preservation of the CB of the
      facial nerve as well as a starting point for retrograde facial nerve dissections.

PMID- 15858772
TI  - Congenital jugular vein phlebectasia.
AB  - BACKGROUND/PURPOSE: The purpose of the present study was to elucidate the
      clinical presentation, diagnosis, treatment, and postoperative complications of
      jugular vein phlebectasia (JVP), and to recommend diagnostic methods and
      treatment choices. MATERIALS AND METHODS: Thirty-six cases of JVP were reviewed
      (right vein in 27, left in 6, and bilateral in 3). The internal jugular veins
      were the most commonly involved. The main complaint was the soft and compressible
      mass in the neck. Ultrasound or color Doppler flow imaging (CDFI) was performed
      on all the children. Surgical intervention was performed in 32 cases, and the
      other 4 cases were conservatively followed up for 4 to 6 years. RESULTS:
      Ultrasound or CDFI demonstrated local dilatation of the unilateral or bilateral
      veins in all the patients. Surgical intervention included ligation of the
      involved jugular vein in 31 cases and draping with medical Dacron cloth in 1
      case. All of the operated children recovered uneventfully, except 3 for cases who
      underwent ligation of the right internal jugular vein. CONCLUSIONS: Valsalva
      maneuver was most important for establishing the diagnosis. Ultrasound or CDFI
      was the diagnostic procedure of choice to confirm the diagnosis of JVP. Surgical
      ligation or excision of unilateral jugular vein was recommended for cosmetic and
      psychological purposes. However, special attention must be paid to prevent
      postoperative complications in case of ligation of right internal jugular vein.
      Or else, treatment should be conservative (follow-up).

PMID- 15858773
TI  - Numerical simulation of intranasal airflow after radical sinus surgery.
AB  - PURPOSE: Radical sinus surgery disturbs intranasal humidification and heating of
      inspired air, resulting in reduced air conditioning mainly caused by a disturbed
      airflow. Therefore, the aim of this study was to simulate the intranasal airflow
      after radical sinus surgery during inspiration by means of numerical simulation.
      MATERIAL AND METHODS: A bilateral model of the human nose with maxillectomy,
      ethmoidectomy, and resection of the lateral nasal wall and the turbinates on one
      side based on a multislice computed tomographic scan was reconstructed. An
      unsteady numerical simulation displaying the intranasal airflow patterns applying
      the computational fluid dynamics solver Fluent 6.1.22 was performed. RESULTS:
      Spacious vortices throughout the entire nasal cavity and the paranasal sinuses
      caused by the radical resections occurred, causing a less-intense contact between
      air and the surrounding nasal wall. An enlargement of the nasal cavity volume and
      a reduction of the nasal surface area in ratio to the nasal cavity volume could
      be observed. CONCLUSIONS: Aggressive sinus surgery leads to disturbed intranasal
      air conditioning caused by disturbed intranasal airflow patterns and a reduction
      of the surface area in relation to the nasal volume. The presented numerical
      simulation demonstrates the close relation between air conditioning and
      intranasal airflow. It can be helpful to understand and interpret in vivo
      measured data of intranasal temperature and humidity.

PMID- 15858774
TI  - Management of nasal bone fractures.
AB  - This review discusses treatment options for nasal fracture, a common condition
      due mainly to road accidents, sport injuries, and physical confrontations. Being
      frequently associated with multiple trauma, many broken noses are not promptly
      diagnosed and treated, leading to secondary nasal deformities and chronic
      obstructions. A description of nasal anatomy is followed by considerations on the
      pathogenesis of nasal fracture and its clinical assessment. Each patient's
      history must be recorded (cause of trauma, previous facial injuries, prior nasal
      deformity, or obstruction) and careful physical examination guides the choice of
      treatment (open vs closed reduction), its timing, and the type of anesthesia
      required. Adequate follow-up is essential. Manipulation under local anesthesia is
      an effective first-line treatment for simple nasal fractures and should become a
      standard practice, but any associated septal injury can be responsible for
      postoperative nasal deformity and obstruction so other options may need to be
      considered.

PMID- 15858775
TI  - Management of the locally aggressive thyroid carcinoma.
AB  - The management of locally advanced thyroid carcinoma can be challenging.
      Differing philosophies exist for the treatment of invasive disease affecting the
      upper aerodigestive tract. The ability to maximize local control and overall
      survival while minimizing the morbidity of a radical resection is the goal of
      care in these patients. This article will review the literature concerning the
      presentation, preoperative evaluation, and the subsite treatment of locally
      aggressive well-differentiated thyroid carcinoma.

PMID- 15858776
TI  - Carcinomatous meningitis arising from primary nasopharyngeal carcinoma.
AB  - Carcinomatous meningitis, also known as leptomeningeal metastasis and meningeal
      carcinomatosis, is the invasion of neoplastic cells into the leptomeninges. Head
      and neck cancers, especially nasopharyngeal carcinoma, give rise to carcinomatous
      meningitis very infrequently. In this case report, we present a rare case of
      carcinomatous meningitis with nasopharyngeal carcinoma as the primary source. In
      1987, a 45-year-old white female presented with a few year history of chronic
      bilateral serous otitis media. She also complained of intermittent diplopia,
      right facial pain, right-sided headache, and, finally, right facial palsy. The
      patient was subsequently diagnosed with nasopharyngeal carcinoma by biopsy and
      treated with radiation as well as chemotherapy. Her neurological symptoms
      improved, and she did fairly well for several years. However, various neurologic
      symptoms started to recur, including right facial weakness, right facial numbness
      in the distribution of all 3 divisions of cranial nerve (CN) V, loss of taste as
      well as smell, and diplopia. In 1993, magnetic resonance imaging scan of the head
      revealed recurrence of nasopharyngeal carcinoma with involvement of the ethmoid
      sinuses as well as extension of the tumor into the frontotemporal leptomeninges.
      Over the course of the next 3 years, the patient experienced a very gradual
      decline with involvement of almost all of the CNs (CN I, II, III, V, VI, VII,
      VIII, IX, X, XII). This case report of carcinomatous meningitis from primary
      nasopharyngeal carcinoma is one of the few reported in the literature. Although
      very rare, nasopharyngeal carcinoma can give rise to carcinomatous meningitis,
      probably by direct invasion of malignant cells. We also review the literature
      with respect to the diagnosis and treatment of carcinomatosis meningitis.

PMID- 15858777
TI  - Nasopharyngeal angiofibroma in an elderly woman.
AB  - "Juvenile" nasopharyngeal angiofibroma is a locally aggressive, yet
      histologically benign, vascular neoplasm. This neoplasm accounts for less than
      0.5% of neoplasms of the head and neck and occurs almost exclusively in
      adolescent males. We report a rare case of a 64-year-old woman with a red
      lobulated mass in the right nostril, diagnosed as nasopharyngeal angiofibroma on
      postoperative histopathologic and immunohistochemical analysis.

PMID- 15858778
TI  - Leiomyosarcoma of the larynx: critical analysis of the diagnostic role played by
      immunohistochemistry.
AB  - Laryngeal leiomyosarcoma (LMS) is definitely considered a rare occurrence: our
      exhaustive literature review disclosed to date only 45 cases (including the new
      case we have reported). The morphological diagnosis of laryngeal LMS may be
      problematic on conventional light microscopy especially in small laryngeal
      specimens. In the past, LMSs of the larynx were frequently confused with other
      spindle-cell malignant tumors. Nowadays, immunohistochemical investigations are
      considered necessary to distinguishing LMS from other spindle-cell tumors. On
      immunostaining, LMS is usually positive for muscle-specific actin and negative
      for cytokeratins and epithelial membrane antigen. In most cases,
      immunohistochemical study allows reliable diagnosis of LMS, but it can produce
      ambiguous or inconclusive results when the tumor cells lack specific
      immunohistochemical reactivity. In these controversial cases, LMS diagnosis has
      to be substantiated by electron microscopy. Distinguishing laryngeal LMS from
      other spindle-cell malignancies plays a role not only in academic interest.
      Confusion in the diagnosis of a spindle-cell laryngeal malignancy could result in
      inappropriate clinical management and inadequate treatment.

PMID- 15858779
TI  - Invasive glomus tumor of the nasal cavity.
AB  - Glomus tumors are neoplasms that occur only rarely in the head and neck. These
      tumors are usually distinguished by benign growth characteristics. We present a
      case of a large intranasal glomus tumor which, at presentation, had eroded
      through the ethmoid roof to involve the floor of the anterior cranial fossa. The
      patient was treated with primary external-beam radiotherapy. To our knowledge,
      this is the first report of an invasive glomus tumor of the head and neck.

PMID- 15858780
TI  - Merkel cell carcinoma of the skin with leptomeningeal metastases.
AB  - Merkel cell carcinoma is a rare skin tumor that is thought to arise from
      epithelial cells that have undergone neuroendocrine differentiation. It usually
      presents in older adults and has a slight male predominance. The most frequent
      site of occurrence is in the head and neck. It is an aggressive disease that has
      a high rate of local-regional and distant recurrence. Optimal treatment is
      controversial but generally consists of surgery and adjuvant radiotherapy. The
      role of chemotherapy is less defined. This report documents the first known case
      of Merkel cell carcinoma with perineural spread to the central nervous system
      with leptomeningeal dissemination. Whether this represents a more aggressive
      variant is unknown. Regardless, this pattern of spread is likely a rare event.

PMID- 15858781
TI  - Multifocal adult rhabdomyoma: a case report and literature review.
AB  - Adult extracardiac rhabdomyoma is an uncommon primary tumor of striated muscle
      origin that almost exclusively presents in the head and neck region. The
      occurrence of multifocality is a rare manifestation of this unusual lesion. In
      this study, we report a rare case of multifocal adult extracardiac rhabdomyoma in
      a patient presenting with an asymptomatic neck mass and provide a brief review of
      the literature on this entity.

PMID- 15858782
TI  - Pleomorphic adenoma of the nasal cavity: clinical analysis of 8 cases.

PMID- 15858783
TI  - Recognition in action: flipping pyrimidine dimers.
AB  - DNA bases are normally sheltered within a double helix, but enzymes that modify
      and repair DNA gain access by flipping individual bases out of the double helix.

PMID- 15858784
TI  - Complexes of diphenylarsinic acid and phenylarsonic acid with thiols: a 1H and
      13C NMR study.
AB  - The high toxicity of diphenylarsinic acid, found in ground water and well water
      as a probable consequence of the inappropriate disposal of warfare agents,
      prompted us to study the reaction, monitored by 1H and 13C NMR spectroscopy, of
      the compound and its monophenyl analogue, phenylarsonic acid, with cellular
      thiols as represented, in particular, by glutathione. Glutathione reduced the
      phenylarsenic acids to trivalent forms and complexed them: diphenylarsinic acid
      to a monoglutathione adduct and phenylarsonic acid to a diglutathione adduct. The
      complexes were characterized by 1H and 13C NMR spectroscopy and mass
      spectrometry. The NMR spectra showed the diastereotopic nature of the two phenyl
      groups in the diphenylarsinic acid-glutathione compound, and of the two
      glutathione residues in the phenylarsonic acid-diglutathione complex. The
      stereochemistry of thiol compounds of phenylarsonic acid was further explored by
      1H and 13C NMR spectroscopy of the L-cysteine complex. The diphenylarsinic acid
      glutathione complex was stable below pH 12 but at higher pH the complex
      dissociated into diphenylarsinous acid and reduced glutathione. The released
      diphenylarsinous acid then oxidized to diphenylarsinic acid with a half-life of
      about 7 h at pH 13 and at room temperature.

PMID- 15858786
TI  - Current literature in diabetes.

PMID- 15858788
TI  - Critical review of oral drug treatments for diabetic neuropathic pain-clinical
      outcomes based on efficacy and safety data from placebo-controlled and direct
      comparative studies.
AB  - The present review aims to evaluate the efficacy and safety of a selection of
      oral treatments for the management of painful diabetic neuropathy. A literature
      review was conducted retrieving placebo-controlled and direct comparative studies
      with a selection of oral treatments for painful diabetic neuropathy. All studies
      were analyzed with regard to efficacy and tolerability. Efficacy was evaluated as
      the percentage improvement in pain intensity between baseline and endpoint.
      Tolerability was evaluated by means of study discontinuations due to adverse
      events and by incidence of drug-related adverse events. The analyzed trials
      enrolled different patient populations with mostly small numbers of patients. The
      great variability in dosages and dose titration schemes, cross-over designs with
      variable wash-out periods, and other design schemes made comparison between the
      different studies difficult. Gabapentin, lamotrigine, tramadol, oxycodone,
      mexiletine, and acetyl-L-carnitine were the only treatments studied in large (at
      least 100 patients), placebo-controlled parallel group trials.It is concluded
      that standardization in design and reporting for comparison of treatments is
      needed. Validated questionnaires for evaluation of the efficacy and safety should
      be further developed. Based on the reviewed randomised controlled trials,
      gabapentin shows good efficacy, a favourable side-effect profile with lack of
      drug interactions and therefore it may be a first choice treatment in painful
      diabetic neuropathy, especially in the elderly. However, head to head trials of
      current treatments are lacking and therefore randomized controlled trials are
      required to address this issue.

PMID- 15858789
TI  - Two-year follow-up intravascular ultrasound analysis after bare metal stent
      implantation in 120 lesions.
AB  - The objective of this study was to examine long-term changes after bare metal
      stent implantation in a relatively large number of patients. There are few
      reports of intravascular ultrasound (IVUS) studies performed on stented and
      nonstented (reference) segments beyond 6 months after bare metal stenting. Using
      IVUS, we evaluated serial changes in stented and reference segments between 6 and
      24 months after stent implantation in 110 patients with 120 lesions. Serial IVUS
      images were acquired at five equidistant intrastent sites and at two different
      reference segment sites. Measurements were made of the external elastic membrane
      (EEM), stent, lumen, and intimal hyperplasia (IH = stent - lumen) area. For the
      whole patient group, between 6 and 24 months, the mean IH area in stented
      segments decreased from 2.6 +/- 1.0 to 2.3 36+/- 0.9 mm2 (P < 0.001), and the
      mean lumen area increased from 6.2 +/- 2.0 to 6.5 +/- 1.9 mm2 (P < 0.001). The
      mean IH area decreased in 91 lesions (76%) and increased in 29 lesions (24%)
      between 6 and 24 months. There were no significant changes in EEM or lumen area
      in the reference segments. Late angiographic restenosis (diameter stenosis > or =
      50%) occurred in three lesions between 6 and 24 months. A late target lesion
      revascularization was performed for one lesion. In the period of time between 6
      and 24 months after stenting, IH regression occurred in most (76%) stent lesions,
      resulting in late lumen increase. However, IH progression was observed in 24% of
      in-stent lesions. No significant changes of EEM or lumen area occurred in the
      reference segments.

PMID- 15858790
TI  - Mysteries behind stent struts.

PMID- 15858791
TI  - Production of recombinant proteins by vaccinia virus in a microcarrier based
      mammalian cell perfusion bioreactor.
AB  - The HeLa cell-vaccinia virus expression system was evaluated for the production
      of recombinant proteins (enhanced green fluorescent protein (EGFP) and HIV
      envelope coat protein, gp120) using microcarriers in 1.5 L perfused bioreactor
      cultures. Perfusion was achieved by use of an alternating tangential flow device
      (ATF), increasing the length of the exponential phase by 50 h compared to batch
      culture and increasing the maximum cell density from 1.5x10(6) to 4.4x10(6)
      cell/mL. A seed train expansion method using cells harvested from microcarrier
      culture and reseeding onto fresh carriers was developed. EGFP was first used as a
      model protein to study process parameters affecting protein yield, specifically
      dissolved oxygen (DO) and temperature during the production phase. The highest
      level of EGFP, 12+/-1.5 microg/10(6) infected cells, was obtained at 50% DO and
      31 degrees C. These setpoints were then used to produce glycoprotein, gp120,
      which was purified and deglycosylated, revealing a significant amount of N-linked
      glycosylation. Also, biological activity was assayed, resulting in an ID50 of 3.1
      microg/mL, which is comparable to previous reports.

PMID- 15858792
TI  - Degradation of aromatic hydrocarbons by white-rot fungi in a historically
      contaminated soil.
AB  - Phanerochaete chrysosporium NRRL 6361 and Pleurotus pulmonarius CBS 664.97 were
      tested for their ability to grow under nonsterile conditions and to degrade
      various aromatic hydrocarbons in an aged contaminated soil that also contained
      high concentrations of heavy metals. After 24 days fungal incubation, carbon-CO2
      liberated, an indicator of microbial activity, reached a plateau. At the end of
      the incubation time (30 days), fungal colonization was clearly visible and was
      confirmed by ergosterol and cell organic carbon determinations. In spite of
      unfavorable pH (around 7.4) and the presence of heavy metals, both fungi produced
      Mn-peroxidase activity. In contrast, laccase and aryl-alcohol oxidase were
      detected only in the soil treated with P. pulmonarius CBS 664.97 and lignin
      peroxidase in that with P. chrysosporium NRRL 6361. No lignin-modifying enzyme
      activities were present in non-inoculated soil incubated for 30 days (control
      microcosm). Regardless of the fungus employed, a total removal of naphtalene,
      tetrachlorobenzene, and dichloroaniline isomers, diphenylether and N-phenyl-1
      naphtalenamine, was observed. Significant release of chloride ions was also
      observed in fungal-treated soil, in comparison with that recorded in the control
      microcosm. Both fungi led to a significant decrease in soil toxicity, as assessed
      using two different soil contact assays, including the Lepidium sativum L.
      germination test and the Collembola mortality test.

PMID- 15858793
TI  - A mathematical model for regulating monomer composition of the microbially
      synthesized polyhydroxyalkanoate copolymers.
AB  - A mathematical model is proposed for predicting the copolymer composition of the
      microbially synthesized polyhydroxyalkanoate (PHA) copolymers. Based on the
      biochemical reactions involved in the precursor formation and polymerization
      pathways, the model correlates the copolymer composition with the cultivation
      conditions, the enzyme levels and selectivity, and the metabolic pathways. It
      suggests the following points: (1) in the case of a sole carbon source, the
      copolymer composition depends mainly on the topology of the metabolic pathways
      and the selectivity of both the enzymes involved in the precursor formation and
      the polymerization route; (2) the copolymer composition can be varied in a wide
      range via alteration of the flux ratio of different types of monomers channeled
      from two or more independent and simultaneous pathways; (3) the enzymes which
      should be over-expressed or inhibited to obtain the desired copolymer composition
      can be predicted. For example, inhibition of the beta-oxidation pathway will
      increase the content of the monomer units with longer chain length. To test the
      model, various experiments were envisaged by varying cultivation time,
      concentration and chain length of the sole carbon source, and molar ratio of the
      cosubstrates. The predictions from the model agree well with the experimental
      results. Therefore, the proposed model will be useful in predicting the PHA
      copolymer composition under different biochemical reaction conditions. In other
      words, it can provide a guide for the synthesis of desired PHA copolymers.

PMID- 15858794
TI  - EGF-induced EGF-receptor and MAP kinase phosphorylation in goat cumulus cells
      during in vitro maturation.
AB  - EGF has been shown to influence meiotic maturation and development competence of
      oocyte in various mammalian species. We previously reported, in goat, that the
      EGF receptor (EGF-R) was present both on cumulus cells and oocytes. Here, EGF
      induced signaling was investigated during the in vitro maturation process in goat
      cumulus-oocyte complexes (COCs). Cumulus cells and oocytes were subjected to
      Western immunoblotting analysis using anti-MAP kinase, anti-phosphotyrosine, anti
      phospho MAP kinase, and anti-phospho EGF-R antibodies. We demonstrated that
      treatment with EGF during the in vitro maturation process induced rapid tyrosine
      phosphorylation of EGF-R in a time and concentration dependent manner in cumulus
      cells. A similar pattern of activation by phosphorylation was observed for MAP
      kinase upon EGF stimulation. AG 1478, an inhibitor of the EGF kinase, suppressed
      EGF-stimulated phosphorylation of EGF-R and also affected the MAP kinase
      activation. Treatment with the MEK inhibitor PD 98059 abolished EGF-induced MAP
      kinase activation. We did not observe oocyte EGF-R phosphorylation in our
      experiments during the in vitro maturation process. Our data indicate, in goat
      cumulus cells, that activation of EGF-R by EGF triggers signaling through the MAP
      kinase pathway during in vitro maturation. This supports the hypothesis that the
      major site of action for EGF, that regulates oocyte maturation, is the cumulus
      cell.

PMID- 15858795
TI  - Characterization and optimization of acoustic filter performance by experimental
      design methodology.
AB  - Acoustic cell filters operate at high separation efficiencies with minimal
      fouling and have provided a practical alternative for up to 200 L/d perfusion
      cultures. However, the operation of cell retention systems depends on several
      settings that should be adjusted depending on the cell concentration and
      perfusion rate. The impact of operating variables on the separation efficiency
      performance of a 10-L acoustic separator was characterized using a factorial
      design of experiments. For the recirculation mode of separator operation,
      bioreactor cell concentration, perfusion rate, power input, stop time and
      recirculation ratio were studied using a fractional factorial 2(5-1) design,
      augmented with axial and center point runs. One complete replicate of the
      experiment was carried out, consisting of 32 more runs, at 8 runs per day.
      Separation efficiency was the primary response and it was fitted by a second
      order model using restricted maximum likelihood estimation. By backward
      elimination, the model equation for both experiments was reduced to 14
      significant terms. The response surface model for the separation efficiency was
      tested using additional independent data to check the accuracy of its
      predictions, to explore robust operation ranges and to optimize separator
      performance. A recirculation ratio of 1.5 and a stop time of 2 s improved the
      separator performance over a wide range of separator operation. At power input of
      5 W the broad range of robust high SE performance (95% or higher) was raised to
      over 8 L/d. The reproducible model testing results over a total period of 3
      months illustrate both the stable separator performance and the applicability of
      the model developed to long-term perfusion cultures.

PMID- 15858796
TI  - Androgen and estrogen treatments alter steady state messengers RNA (mRNA) levels
      of testicular steroidogenic enzymes in the rainbow trout, Oncorhynchus mykiss.
AB  - Recent investigations have shown that estrogens have profound inhibitory effects
      on steroidogenic enzyme gene expressions before and after testicular
      differentiation in the rainbow trout, Oncorhynchus mykiss. This present study
      bring new data on juvenile rainbow trout treated with estrogens and androgens.
      Following a 8 days oral treatment of juvenile male with 17alpha-ethynyl-estradiol
      (EE2, 20 mg/kg diet) or 11beta-hydroxyandrostenedione (11betaOHDelta4, 10 mg/kg
      diet), we observed a fast and marked decrease of steady-state mRNA levels for
      3betaHSD, P450scc, P450c17, and P450c11 enzymes in the testis. After completion
      of these treatments, mRNA levels of these enzymes remained low in EE2 treated
      males whereas in 11betaOHDelta4 treated males they recovered their initial levels
      in 8 days. This demonstrate that both androgen and estrogen treatments have
      profound effects on testicular steroidogenesis by decreasing steroid enzymes
      steady-state mRNA. After in vitro incubation of testicular explants with 17beta
      estradiol (E2, 600 ng/ml of medium), we also observed a decrease of mRNA levels
      for 3betaHSD and P450c11. This suggest that estrogens effects could be triggered,
      at least to some extend, directly on the testis. We also investigated the
      hypothesis of a negative feedback of steroids on follicle stimulating hormone
      (FSH) secretion, but FSH plasmatic levels in treated fish did not showed any
      significant decrease. This demonstrate that FSH is not implied in this steroids
      inhibition of steroidogenic enzymes gene expression.

PMID- 15858797
TI  - Fully grown mouse oocyte contains transcription inhibiting activity which acts
      through histone deacetylation.
AB  - Mouse ovarian oocytes remain transcriptionally active during the entire period of
      oocyte growth. In the fully grown antral oocytes, RNA synthesis is terminated
      before initiation of maturation. The mechanism involved in this process remains
      unknown. It was proposed that some signals provided by companion granulosa cells,
      and accumulating in the cytoplasm of the oocyte, play a role in the termination
      of RNA synthesis. It seems possible that under influence of these signals, the
      oocyte cytoplasm becomes transcriptionally nonpermissive. In the present study,
      transcriptionally active, single blastomeres of the 8-cell mouse embryo were
      fused with nontranscribing fully grown oocytes, and RNA synthesis was analyzed in
      the resulting hybrids. We show that after 27 hr of culture of hybrid cells,
      transcription in the blastomere nuclei was finally silenced. This process occurs
      without nuclear envelope breakdown and is accompanied by progressive condensation
      of the chromatin in the blastomere nuclei. We show also the involvement of core
      histone deacetylation in the modification of chromatin configuration and
      termination of RNA synthesis in the blastomere nuclei.

PMID- 15858798
TI  - Effect of coadministration of parenteral multivitamins with lipid emulsion on
      lung remodeling in an animal model of total parenteral nutrition.
AB  - Exposure of parenteral multivitamin solutions (MVP) to ambient light generates
      peroxides and vitamin loss, and induces initiation of fibrosis and a reduced
      alveolar count in an animal model of total parenteral nutrition (TPN). Adding MVP
      to the lipid moiety of TPN prevents lipid peroxidation and vitamin loss. The aim
      of the study was to compare modes of delivery of MVP on lung procollagen mRNA and
      alveolar counts. Three-day-old guinea pig pups were infused continuously with one
      of three intravenous solutions: 1) control = dextrose; 2) AA + MVP = MVP given
      with the dextrose + amino-acid moiety, in a "piggyback" setup with a lipid
      emulsion mixed close to the infusion site; and 3) LIP + MVP = same as AA + MVP,
      except that MVP is given with the lipid emulsion. After 4 days, lungs were
      prepared for alveolar count (intercept technique) and for quantification of the
      procollagen/beta-actin mRNA ratio (initial step of fibrosis). Data were compared
      by ANOVA. The procollagen mRNA was lower (P < 0.05) in animals receiving LIP +
      MVP than those with AA + MVP. But the two modes of admixture of MVP had the same
      effect on the alveolar counts, which were lower (P < 0.01) than controls. The
      mode of delivery of TPN affects lung remodeling. Although LIP + MVP protects
      against the initiation of lung fibrosis, the absence of a beneficial effect on
      alveolar counts suggests that these features of lung remodeling are not caused by
      a unique component of TPN. Specific roles of peroxides, components of MVP, and
      light exposure on lung remodeling need to be explored before LIP + MVP can be
      recommended as an alternative mode of parenteral vitamin delivery.

PMID- 15858799
TI  - Decreased physical activity among Head Start children with a history of wheezing:
      use of an accelerometer to measure activity.
AB  - Asthma is a severe problem among inner city children, and recent evidence
      suggests that both allergen exposure and lifestyle can impact the disease early
      in childhood. This study was designed to investigate the association between
      physical activity and wheezing among a population of inner city children
      enrolling in Head Start. The parents of children aged 3-5 years responded to a
      questionnaire (N = 144) to determine the presence and severity of wheezing and
      asthma. Information was also gathered regarding home environment, food frequency,
      and presence of other allergic diseases. Serum was obtained to measure total IgE
      and specific IgE levels to common allergens. Height and weight for body mass
      index were recorded. Lastly, motion sensor wristwatches (Actiwatch) were worn
      continuously by a subset of these children (n = 54) for 6 or 7 days. Physical
      activity measured with the motion sensor was decreased among children with a
      history of wheezing. The significant differences involved those measures of
      activity relating to prolonged or sustained physical activity. The correlates of
      asthma associated with decreased levels of physical activity included: 1) a
      history of wheezing in the last 12 months, 2) the diagnosis of asthma, and 3)
      presentation to the emergency room in the last 12 months for wheezing or asthma.
      In a preschool-age population, decreased physical activity was observed among
      children with a history of asthma or wheezing. Decreased physical activity could
      contribute to persistence of asthma or put children at higher risk for obesity
      and other chronic diseases.

PMID- 15858800
TI  - Limitations of electronic compensation for measuring plethysmographic airway
      resistance in infants.
AB  - Electronic compensation to overcome thermal artifacts during plethysmographic
      estimations of airway resistance is now used routinely in adults and school-age
      children, and was shown to be a valuable means of discriminating airway function
      between preschool children with and without lung disease. A similar system is now
      commercially available for infants, which could increase the applicability of
      this technique. However, we noted marked discrepancies in electronically
      calculated values of airway resistance in this age group, both with respect to
      absolute values displayed and marked within-subject variability on a single test
      occasion. The aim of this technical report is to summarize our recent findings in
      order to alert other users to potential problems. Airway resistance (R(aw)) was
      measured in 62 infants (28 with cystic fibrosis (CF); 34 healthy). Three to five
      epochs of quiet regular tidal breathing were collected in each infant. Marked
      within-subject, within-test variability was observed, with the median coefficient
      of variation (CV) being 9.1% (range, 1.2-52.6%) within and 8.5% (0.1-112%)
      between epochs. Among healthy infants, R(aw) varied from 0.1-6.4 (kPa x liter(-1)
      x sec), with no relationship to either body or lung size and complete overlap of
      results with those from infants with CF, despite abnormal lung function in the
      latter when assessed by other means. The marked within- and between-subject
      variability in healthy infants, and lack of discriminative power of R(aw) when
      derived from electronically compensated values, currently preclude application in
      either clinical or research studies.

PMID- 15858801
TI  - Association between botulinum toxin injection into the arm and changes in gait in
      adults after stroke.
AB  - Botulinum toxin (BTX) is often used to improve arm function in persons with
      hemiparesis after stroke. Persons injected into the arm sometimes report changes
      in their gait. The purpose of this open-labeled pilot study was to investigate
      the association between injecting BTX into the upper limb and ankle and knee
      range of motion (ROM) and paretic-leg stride-time, defined as the time in seconds
      required to move the hemiparetic leg from initial contact of the foot to initial
      contact of the same foot. Gait parameters were recorded before and 4 to 6 weeks
      after the hemiparetic arm was injected with BTX in 13 adults with hemiparesis
      secondary to stroke, using a three-dimensional computerized motion analysis
      system. BTX injection into the paretic arm was associated with a decrease in
      stride-time of the paretic leg in all participants. Slower striding participants
      improved knee and ankle ROM in the paretic leg. There was no change in ankle and
      knee ROM in faster striding participants. Injection of BTX into the upper
      extremity is associated with a change in hemiparetic leg stride-time and ankle
      and knee ROM. There is a variability of response, with slow striders improving to
      a greater extent than fast striders.

PMID- 15858802
TI  - Nontuberculous mycobacterial infection in young children with cystic fibrosis.
AB  - Although nontuberculous mycobacteria (NTM) are recognized pathogens in adolescent
      and adult patients with cystic fibrosis (CF), the role of NTM in younger CF
      patients is not well-defined. To explore NTM infection in CF patients less than
      12 years old, a retrospective review was performed. Prevalence was estimated from
      routine mycobacterial cultures of bronchoalveolar lavage (BAL) specimens
      collected over a 3-year period. NTM-positive cultures were obtained from 9 of 258
      BALs collected from 7 of 114 different patients (5 months to 11 years of age).
      Further data were acquired from microbiological and clinical records of all
      pediatric patients with CF over a 10-year period. A total of 17 patients had at
      least one positive mycobacterial culture at less than 12 years of age, 5 of whom
      had positive cultures before age 5. The most commonly identified organisms were
      Mycobacterium avium-complex and Mycobacterium abscessus. Of the 17 patients, 10
      met American Thoracic Society (ATS) microbiological criteria for mycobacterial
      disease, and 7 did not. The two groups did not differ with respect to age,
      gender, or presence of other respiratory pathogens. Patients who met ATS
      microbiological criteria for disease were more likely to have positive smears for
      acid-fast bacilli and grow Mycobacterium abscessus from culture. These patients
      also had a greater decline in lung function over time than patients who did not
      meet the microbiologic criteria. These data suggest that NTM represent a
      clinically significant pathogen, even in young patients with cystic fibrosis.

PMID- 15858803
TI  - Addiction in Parkinson's disease: impact of subthalamic nucleus deep brain
      stimulation.
AB  - In Parkinson's disease, dopamine dysregulation syndrome (DDS) is characterized by
      severe dopamine addiction and behavioral disorders such as manic psychosis,
      hypersexuality, pathological gambling, and mood swings. Here, we describe the
      case of 2 young parkinsonian patients suffering from disabling motor fluctuations
      and dyskinesia associated with severe DDS. In addition to alleviating the motor
      disability in both patients, subthalamic nucleus (STN) deep brain stimulation
      greatly reduced the behavioral disorders as well as completely abolished the
      addiction to dopaminergic treatment. Dopaminergic addiction in patients with
      Parkinson's disease, therefore, does not constitute an obstacle to high-frequency
      STN stimulation, and this treatment may even cure the addiction.

PMID- 15858804
TI  - Validation of a pediatric caregiver diary to measure symptoms of postacute
      respiratory syncytial virus bronchiolitis.
AB  - Acute respiratory syncytial virus (RSV)-induced bronchiolitis is often associated
      with continuing respiratory symptoms following hospitalization. To date, there is
      no validated objective measure to evaluate symptoms of RSV-induced bronchiolitis.
      We report on the reliability, validity, and responsiveness of the bronchiolitis
      caregiver diary (BCD) of symptoms and healthcare utilization associated with
      postacute RSV. The BCD measures four symptoms (daytime cough, wheeze, trouble
      breathing, and nighttime cough), healthcare utilization, and rescue medication
      for worsening of lung symptoms. Data from the 4-week treatment period of the
      reported prospective, placebo-controlled trial of montelukast for treatment of
      postacute RSV were used to assess reliability (internal consistency and test
      retest), construct validity (cross-sectional and longitudinal correlations),
      discriminant validity (known-groups analyses), and responsiveness. The primary
      outcome of this study was the percentage of symptom-free days (SFD). The
      secondary outcome was a composite symptom score (CSS; average of daytime cough,
      wheezing, and trouble breathing). Cronbach's alpha of 0.85 indicated that the
      four symptoms were internally consistent, supporting a unidimensional scale
      structure. Test-retest reliabilities for the percentage of SFD and CSS were above
      the recommended cut point of 0.70. Cross-sectional and longitudinal correlations
      were sizeable and statistically significant, demonstrating construct validity.
      Hypothesized known-group differences were statistically significant in the
      appropriate direction. Responsiveness analyses indicated moderate effect sizes
      for percentage of SFD. In conclusion, the BCD provides a valid, reliable, and
      responsive tool for the assessment of symptoms of postacute RSV-induced
      bronchiolitis, capable of measuring moderate effect sizes, and demonstrating
      responsiveness to therapy.

PMID- 15858805
TI  - Polysomnographic values in children 2-9 years old: additional data and review of
      the literature.
AB  - The establishment of normal pediatric polysomnographic parameters is important
      for both clinical and research interests. Our objectives were to describe
      respiratory events, paradoxical breathing, periodic limb movements, and sleep
      architecture of children at the age of peak incidence of obstructive sleep apnea
      syndrome. We performed a retrospective cross-sectional analysis of a prospective
      cohort study of 66 children, 2-9 years old, at the Sleep Disorders Center at the
      Children's Hospital of Philadelphia. Subjects screened by questionnaire underwent
      a standard polysomnogram. The percent of total sleep time spent in sleep stages
      1, 2, 3, 4, and rapid eye movement (REM) were 4 +/- 3%, 44 +/- 10%, 10 +/- 6%, 22
      +/- 8%, and 21 +/- 6%, respectively. The arousal and awakening index was 11.2 +/-
      4.3/hr. Respiratory events included a central apnea index of 0.08 +/- 0.14/hr,
      obstructive apnea index of 0.01 +/- 0.03/hr, and obstructive hypopnea index of
      0.3 +/- 0.5/hr. The baseline arterial oxygen saturation (SpO2) was 97 +/- 1%,
      with a nadir of 92 +/- 3%. The index of periodic limb movements in sleep (PLMS)
      was 1.3 +/- 2.2/hr. Paradoxical breathing appeared significantly more frequent
      with piezo crystal effort belts (40 +/- 24% of epochs) than with respiratory
      inductive plethysmography (1.5 +/- 3% of epochs). We describe the occurrence of
      hypopneas during sleep, arousals and awakenings, and PLMS. We illustrate how
      different technologies can vary the apparent amount of paradoxical breathing. We
      also confirm previous data on the frequency distribution of sleep stages, SpO2,
      and relative rarity of respiratory events in this age group.

PMID- 15858806
TI  - Bilateral internuclear ophthalmoplegia in progressive supranuclear palsy with an
      overriding oculocephalic maneuver.
AB  - We present a patient with progressive supranuclear palsy (PSP) who had a
      bilateral internuclear ophthalmoplegia (INO) that could be fully overcome by the
      oculocephalic maneuver. In addition to being an unusual finding in the clinical
      setting of PSP, this phenomenon has interesting implications for the functional
      control of conjugate horizontal gaze.

PMID- 15858807
TI  - Classification conundrums in paroxysmal dyskinesias: a new subtype or variations
      on classic themes?
AB  - Paroxysmal movement disorders are a group of heterogeneous entities that have
      been categorized based on their most salient features. The four classic
      categories of paroxysmal dyskinesias are kinesigenic, nonkinesigenic, hypnogenic,
      and exercise-induced. The phenotypic variability of these disorders, coupled with
      new insights into their possible etiologies, has made the task of classification
      increasingly problematic. We describe 4 cases that do not fit easily into the
      current classification scheme, compare them with four others recently described
      in the literature, and raise the question as to whether they constitute a new
      subtype.

PMID- 15858808
TI  - Cytokine levels in sputum of cystic fibrosis patients before and after antibiotic
      therapy.
AB  - It is not known whether cytokine levels in sputum may be used as outcome measures
      after parenteral antibiotic therapy in cystic fibrosis (CF) patients. Here, we
      assessed the effects of antibiotic therapy on cytokine levels in sputum and serum
      obtained from young CF patients. Thirty-two CF patients (14 females; mean age,
      18.6 years; range, 11.4-35.7 years), consecutively admitted at the CF Center of
      Milan for parenteral antibiotic therapy during pulmonary exacerbation, were
      enrolled in the study. Before and after 21 days (range, 5-41) of intravenous
      antibiotic treatment, all patients underwent routine laboratory determinations
      (including white blood cell (WBC) count and C-reactive protein (CRP)), a chest X
      ray, pulmonary function tests (forced expiratory volume in 1 sec (FEV1) and
      forced vital capacity (FVC) as % predicted), and sputum cultures. Interleukin
      (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha levels in serum and
      sputum samples were determined by means of immunometric assays. After therapy,
      FEV1 and FVC significantly improved (median increase of 7.5% and 8.5% predicted,
      respectively), while CRP and WBC count were significantly decreased (median
      values from 14 to 5.5 mg/dl and from 8,350 to 7,400 n/mm3, respectively). While
      levels of IL-6 and IL-10 in sputum were generally undetectable, IL-8 and TNF
      alpha were always measurable, and IL-8 levels significantly decreased after
      antibiotic treatment (median values from 7,165 to 5,415 pg/ml). Following
      antibiotic therapy, IL-8 and TNF-alpha levels in sputum were inversely related
      with both FEV(1) and FVC. In conclusion, TNF-alpha and IL-8 levels in sputum of
      young CF patients with pulmonary exacerbation were always detectable and may be
      useful, noninvasive outcome measures to assess response to therapy in CF
      patients.

PMID- 15858809
TI  - Direct comparison between regional cerebral metabolism in progressive
      supranuclear palsy and Parkinson's disease.
AB  - The differentiation between progressive supranuclear palsy (PSP) and Parkinson's
      disease (PD) may be difficult, especially in the early stages of disease.
      Positron emission tomography potentially provides a tool for making such a
      distinction. To identify key features in the spatial distributions of cerebral
      glucose metabolism, 18F-fluorodeoxyglucose (FDG) measurements of 10 patients with
      probable or possible PSP were directly compared with those of 9 PD patients. This
      analysis was done with statistic parametric mapping. After normalization of
      global brain uptake, in PSP, relative uptake of FDG was reduced in the caudal
      (motor) part of the anterior cingulate gyrus (Brodmann's area BA 24; P < 0.05,
      corrected for multiple comparisons). At a lower threshold, an additional decrease
      was present in the dorsal mesencephalon. In PD, relative hypometabolism was seen
      in extrastriate visual, ventrolateral temporal, posterior parietal, and
      orbitofrontal regions. Only reduction in the right fusiform gyrus and the lateral
      extrastriate visual cortex reached statistical significance. We concluded that
      particularly the reduction of medial frontal metabolism may be a valuable
      diagnostic imaging parameter in distinguishing PSP from PD. For PD, a possible
      association between occipitotemporal FDG decrease and vulnerability to
      hallucinations is suggested.

PMID- 15858810
TI  - Clinical and genetic study of a large SPG4 Italian family.
AB  - A novel SPG4 906delT frame-shift mutation in exon 6 was identified in a large
      Italian family with an autosomal dominant form of hereditary spastic paraplegia
      (ADHSP). Intrafamilial phenotypic variations observed in the pedigree included
      spasticity and additional clinical features, such as peripheral sensory-motor
      neuropathy, cognitive impairment, and urological dysfunction. Severe clinical
      features were found predominantly in the men who were affected, and there was no
      statistically significant correlation of disability and time since onset of
      symptoms, suggesting the existence of other genetic/nongenetic modifier(s),
      including gender.

PMID- 15858811
TI  - Episodes of hypoxemia during synchronized intermittent mandatory ventilation in
      ventilator-dependent very low birth weight infants.
AB  - Distinct patterns of asynchrony, and episodes of hypoxemia, may occur in a
      spontaneously breathing preterm infant during conventional intermittent mandatory
      ventilation (IMV) on traditional time-cycled, pressure-limited ventilators.
      Synchronized IMV (SIMV) and assist/control ventilation are frequent modes of
      patient-triggered ventilation used with infant ventilators. The objective of this
      study was to use computerized pulse oximetry to quantify the occurrence of
      episodes of hypoxemia (oxygen desaturation) during SIMV vs. IMV, in preterm
      infants < or = 1,250 g who required mechanical ventilation at > or = 14 days of
      age. We performed a randomized, crossover study with each infant being randomized
      to IMV or SIMV (Infant Star ventilator) for initial testing for a 1-hr period.
      Patients were subsequently tested on the alternate modality after a stabilization
      period of 10 min at the same ventilator and fractional inspired oxygen
      concentration (FiO2) settings. Pulse oximetry data were obtained with a Nellcor N
      200 monitor, a microcomputer, and a software program (SatMaster). An investigator
      blinded to the randomized assignment evaluated all measurements. Eighteen very
      low birth weight (VLBW) infants with a birth weight of 777 +/- 39 g (mean +/-
      SEM) and gestational age 25.1 +/- 0.3 weeks were studied. The average pulse
      oximeter oxygen saturation (SaO2) was higher on SIMV than IMV (P < 0.01). During
      SIMV, these infants had significantly fewer episodes of hypoxemia (duration of
      episodes of oxygen desaturation as a percentage of scorable recording time) to 86
      90% SaO2 (P < 0.01), 81-85% SaO2 (P < 0.01), and 76-80% SaO2 (P < 0.05) when
      compared to IMV. There was also a significant decrease in percentage of time of
      desaturation to SaO2 < 90% (P = 0.002), < 85% SaO2 (P = 0.003), and < 80% SaO2 (P
      = 0.02) during SIMV vs. IMV. Our preliminary findings indicate that the use of
      SIMV in a population of VLBW ventilator-dependent infants (> or = 14 days of age)
      results in better oxygenation and decreased episodes of hypoxemia as compared to
      IMV.

PMID- 15858812
TI  - Cystic fibrosis and airway submucosal glands.
AB  - The chronic pulmonary infections and inflammation associated with cystic fibrosis
      (CF) are responsible for almost all the morbidity and mortality of this disease.
      Our understanding of the mechanisms that underlie the very early stages of CF
      lung disease, that result directly from mutations in the CF gene, is relatively
      poor. However, the demonstration that the predominant sites of expression of the
      CF gene in normal lungs are the submucosal glands, together with the histological
      observations showing that hyperplasia of these glands and mucin occlusion of the
      gland ducts are the earliest signs of disease in the CF lung, suggest that
      malfunction of the submucosal glands may be an important factor contributing to
      the early pathophysiology of CF lung disease. This review describes the function
      of submucosal glands in normal lungs, and the way in which their function may be
      disrupted in CF and may thus contribute to the early stages of CF lung disease.

PMID- 15858813
TI  - Association studies between risk for late-onset Alzheimer's disease and variants
      in insulin degrading enzyme.
AB  - Linkage studies have suggested there is a susceptibility gene for late onset
      Alzheimer's disease (LOAD) in a broad region of chromosome 10. A strong
      positional and biological candidate is the gene encoding the insulin-degrading
      enzyme (IDE), a protease involved in the catabolism of Abeta. However, previous
      association studies have produced inconsistent results. To systematically
      evaluate the role of variation in IDE in the risk for LOAD, we genotyped 18 SNPs
      spanning a 276 kb region in and around IDE, including three "tagging" SNPs
      identified in an earlier study. We used four case-control series with a total of
      1,217 cases and 1,257 controls. One SNP (IDE_7) showed association in two samples
      (P-value = 0.0066, and P = 0.026, respectively), but this result was not
      replicated in the other two series. None of the other SNPs showed association
      with LOAD in any of the tested samples. Haplotypes, constructed from the three
      tagging SNPs, showed no globally significant association. In the UK2 series, the
      CTA haplotype was over-represented in cases (P = 0.046), and in the combined data
      set, the CCG haplotype was more frequent in controls (P = 0.015). However, these
      weak associations observed in our series were in the opposite direction to the
      results in previous studies. Although our results are not universally negative,
      we were unable to replicate the results of previous studies and conclude that
      common variants or haplotypes of these variants in IDE are not major risk factors
      for LOAD.

PMID- 15858814
TI  - Bilateral stimulation of nucleus subthalamicus in advanced Parkinson's disease:
      no effects on, and of, autonomic dysfunction.
AB  - It is not known whether bilateral stimulation of the subthalamic nucleus,
      performed to improve skeletal motor control in advanced Parkinson's disease, also
      affects central autonomic regulation of cardiovascular motor function.
      Furthermore, reduced treatment with dopaminergic and other drugs after bilateral
      stimulation of the subthalamic nucleus could affect cardiovascular autonomic
      reflexes and/or other factors controlling blood pressure level. The primary aim
      of this study was to investigate putative effects of bilateral stimulation of the
      subthalamic nucleus on the autonomic nervous system, using respiratory heart rate
      variability and blood pressure responses to tilt as indices. Baseline autonomic
      tests were performed in 19 patients with Parkinson's disease and 10 matched
      healthy subjects. Patients were divided in two groups and re-investigated after 1
      year of optimized pharmacological treatment (n = 8) or 1 year of bilateral
      subthalamic nucleus stimulation (n = 11). Both skeletal motor dysfunction and
      dopaminergic drug treatment were significantly reduced after 1 year of bilateral
      subthalamic nucleus stimulation. However, heart rate variability as well as blood
      pressure during tilt was reduced compared to baseline to a similar extent in both
      patient groups. The number of individual patients showing pathological autonomic
      test results at 1-year follow-up increased only in the subthalamic nucleus
      stimulation group. Despite reduced pharmacological treatment and reduced motor
      disability, bilateral subthalamic nucleus stimulation does not improve
      cardiovascular autonomic reflex function or protect against development of
      cardiovascular autonomic failure in Parkinson's disease. Preoperative
      cardiovascular autonomic reflex dysfunction, conversely, does not exclude an
      excellent stimulation effect.

PMID- 15858815
TI  - Cognitive functions correlate with white matter architecture in a normal
      pediatric population: a diffusion tensor MRI study.
AB  - A possible relationship between cognitive abilities and white matter structure as
      assessed by magnetic resonance diffusion tensor imaging (DTI) was investigated in
      the pediatric population. DTI was performed on 47 normal children ages 5-18.
      Using a voxelwise analysis technique, the fractional anisotropy (FA) and mean
      diffusivity (MD) were tested for significant correlations with Wechsler full
      scale IQ scores, with subject age and gender used as covariates. Regions
      displaying significant positive correlations of IQ scores with FA were found
      bilaterally in white matter association areas, including frontal and occipito
      parietal areas. No regions were found exhibiting correlations of IQ with MD
      except for one frontal area significantly overlapping a region containing a
      significant correlation with FA. The positive direction of the correlation with
      FA is the same as that found previously with age, and indicates a positive
      relationship between fiber organization and/or density with cognitive function.
      The results are consistent with the hypothesis that regionally specific increased
      fiber organization is a mechanism responsible for the normal development of white
      matter tracts.

PMID- 15858816
TI  - Physicians' communication with a cancer patient and a relative: a randomized
      study assessing the efficacy of consolidation workshops.
AB  - BACKGROUND: Although patients with cancer are often accompanied by a relative
      during medical interviews, to the authors' knowledge little is known regarding
      the efficacy of communication skills training programs on physicians'
      communication skills in this context. The objective of the current study was to
      assess the efficacy of 6 consolidation workshops, 3 hours in length, that were
      conducted after a 2.5-day basic training program. METHODS: After attending the
      basic training program, physicians were assigned randomly to consolidation
      workshops or to a waiting list. Training efficacy was assessed through simulated
      and actual interviews that were recorded on an audio tape at baseline, after
      consolidation workshops for the consolidation-workshops group, and 5 months after
      the end of basic training for the waiting-list group. Communication skills were
      assessed according to the Cancer Research Campaign Workshop Evaluation Manual.
      Patients' and relatives' perceptions of and satisfaction with physicians'
      communication performance were assessed using a 15-item questionnaire. RESULTS:
      Sixty-two physicians completed the training program. Compared with physicians who
      participated to the basic training program, when addressing the patient,
      physicians who were randomized to the consolidation workshops used more open,
      open directive, and screening questions (P = 0.011 in simulated patient
      interviews and P = 0.005 in actual patient interviews) and elicited and clarified
      psychologic concerns more often (P = 0.006 in simulated patient interviews and P
      < 0.001 in actual patient interviews). When they addressed the relative,
      physicians who were randomized to the consolidation workshops gave less premature
      information (P = 0.032 in simulated patient interviews and P < 0.001 in actual
      patient interviews). When they addressed the patient and the relative
      simultaneously, physicians who were randomized to the consolidation workshops
      used more empathy, educated guesses, alerting to reality, confronting,
      negotiating, and summarizing (P = 0.003 in simulated patient interviews and P =
      0.024 in actual patient interviews). Patients, but not relatives, who interacted
      with physicians in the consolidation-workshops group were more satisfied globally
      with the interviews (P = 0.022). CONCLUSIONS: Six 3-hour consolidation workshops
      resulted in improved communication skills addressed to patients and to relatives.
      The current results showed that the transfer of skills addressing relatives'
      concerns remained limited and that consolidation workshops should focus even more
      systematically on the practice of three-person interviews.

PMID- 15858817
TI  - Comparative proteomic analysis identifies protein disulfide isomerase and
      peroxiredoxin 1 as new players involved in embryonic interdigital cell death.
AB  - In this study, we used comparative proteomics to identify proteins that were
      involved in the regulation of interdigital cell death. The protein profiles of
      embryonic day (E) 12.5 and 13.5 mouse hindlimb interdigital tissues were compared
      to identify proteins that were differentially expressed. The interdigital cells
      are irreversibly committed to programmed cell death (PCD) at E13.5, whereas they
      are developmentally plastic at E12.5. We established that protein disulfide
      isomerase (PDI) expression was up-regulated at E13.5, while peroxiredoxin 1
      (Prdx1) expression was down-regulated at this time point. Semiquantitative
      reverse transcriptase-polymerase chain reaction and Western blot analyses
      confirmed the data obtained from the two-dimensional electrophoresis gels.
      Furthermore, we were able to up-regulate PDI expression by manipulating the E12.5
      interdigital tissues to die during culture, although this up-regulation was not
      possible when cell survival was promoted. In addition, we could inhibit
      interdigital cell death and expression of proapoptotic genes (Bmp-4 and Bambi) by
      treating interdigital tissues with PDI antibodies and bacitracin (a PDI enzyme
      inhibitor). These findings suggested that PDI was involved in the activation and
      maintenance of interdigital cell death. Conversely, we determined that Prdx1
      expression was maintained when interdigital cultures were manipulated to survive
      but down-regulated when the cultures were permitted to die. The result suggested
      that Prdx1 was involved in maintaining interdigital cell survival. However, we
      were unable to induce interdigital cell death by means of RNA interference
      mediated silencing of Prdx1 expression, indicating that Prdx1 down-regulation is
      not sufficient for PCD to occur. Proteomic analysis of the Prdx1 knock-down cells
      revealed that the level of NF-kappaB inhibitor epsilon (IkappaBepsilon) was
      dramatically reduced. Furthermore, we found an increase in NFkappaB activation
      and reactive oxygen species (ROS) levels in the cytoplasm as a result of Prdx1
      knockdown. We also found that silencing Prdx1 made the interdigital cells more
      susceptible to ROS-induced cell death. Taken together, our study identifies two
      new players in interdigital cell death and highlights that PCD is regulated by a
      delicate balance of proapoptotic and survival-promoting activities.

PMID- 15858818
TI  - Shh signaling in limb bud ectoderm: potential role in teratogen-induced postaxial
      ectrodactyly.
AB  - A variety of teratogens induce the loss of postaxial forelimb structures when
      administered during mid-gestation to the mouse. Previous studies demonstrated
      that teratogen exposure is associated with a reduction in zone of polarizing
      activity (ZPA) -related polarizing activity without a noticeable loss of Shh
      expression. Herein, we quantitatively confirm that expression of Shh, Ptch1, and
      Gli3 are unaltered by teratogen exposure and demonstrate that sonic hedgehog
      (Shh) translation is unaffected. Examination of the polarizing response of host
      chick wings to teratogen-exposed ZPA tissue revealed an induced growth response
      and ectopic induction of Fgf4, Bmp2, Ptch1, and Gli1 expression similar to
      control ZPA tissue. Control ZPA tissue altered the fate of cells destined to die
      in the anterior necrotic zone, whereas cell death ensued in hosts receiving
      teratogen-exposed grafts. Immunohistochemical studies localized Shh protein in
      the mouse limb to the posterior mesoderm and overlying ectoderm. We postulate
      that teratogen exposure alters the ability of Shh to signal to the ectoderm and
      present microarray and reverse transcriptase-polymerase chain reaction data,
      indicating that Shh signaling could occur in the limb bud ectoderm.

PMID- 15858819
TI  - Serotonin transporter: evolution and impact of polymorphic transcriptional
      regulation.
AB  - The serotonin transporter (SERT) is the primary drug target in the current
      antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT
      gene encoding the SERT has been identified and associated with susceptibility to
      affective disorders and treatment response to antidepressants. This study
      addresses the possible impact of the variable number of tandem repeats (VNTR) to
      behavior and disease by examining the evolutionary origin and mechanisms of
      differential transcriptional regulation of SERT. We trace the evolutionary origin
      of the VNTR and show that it is present and varies extensively across the great
      apes and monkeys as well as in rodents while it is absent in non-mammals. As in
      humans, the VNTR sequence may be polymorphic within species and thus it may
      underlie both inter- and intraspecies differences. Also, we find new putative
      binding sites for several transcription factors in the VNTRs of all mammalian
      SERT genes. The number of these putative binding sites varies proportionally to
      the length of the VNTR. We propose that the intronic VNTR have been selectively
      targeted through mammalian evolution to finetune transcriptional regulation of
      the serotonin expression.

PMID- 15858820
TI  - Dihydropyrimidinase-related protein 2 (DRP-2) gene and association to deficit and
      nondeficit schizophrenia.
AB  - A previous study has shown an association between the *2236T > C allele
      polymorphism of the dihydropyrimidinase-related protein 2 (DRP-2) gene and
      schizophrenia in a Japanese sample [Nakata et al. (2003); Biological Psychiatry
      53:571-576]. DRP-2 is an important molecule in guiding neuronal development and
      its gene is located in 8p21, a chromosomal region that was previously shown to
      have significant linkage to schizophrenia and to several deficit symptoms of
      schizophrenia. We compared the frequency of the DRP-2 *2236T > C polymorphism
      between subjects with (n = 117) and without (n = 72) schizophrenia, and then
      further evaluated whether the association was specific for the deficit (n = 24)
      and nondeficit (n = 93) forms of schizophrenia. In both Caucasians and African
      Americans, the C allele occurred more frequently in schizophrenia cases than
      controls, with this difference achieving statistical significance in Caucasians
      (C allele frequency: 42.0% in cases vs. 25.0% in controls, P = 0.014) but not
      African Americans (52.6% in cases vs. 50.0% in controls, P = 0.93). In
      Caucasians, the frequency of the C allele was significantly higher in both the
      deficit (allele frequency 53.3%, P = 0.009) and nondeficit (39.2%, P =0.050)
      forms of schizophrenia compared to controls (allele frequency 25.0%). We conclude
      that the DRP-2 *2236 C allele may mark another polymorphism in DRP-2, or in a
      nearby gene, that may influence susceptibility to schizophrenia.

PMID- 15858821
TI  - Mutation screening of a haplotype block around the insulin degrading enzyme gene
      and association with Alzheimer's disease.
AB  - Genetic and biological studies point to a role for insulin-degrading enzyme (IDE)
      in Alzheimer's disease (AD). Two SNP-based studies recently reported evidence for
      association with AD using markers in a approximately 270 kb haplotype block on
      chromosome 10q. This haplotype block region harbors three known genes; insulin
      degrading enzyme (IDE), kinesin family member 11 (KIF11), and hematopoietically
      expressed homeobox (HHEX). In an attempt to search for susceptibility variants we
      have sequenced all coding exons, 2 kb of 5' and 3'-flanking sequence, and all
      regions showing a high degree of human-mouse conservation in these three genes in
      30 individuals. We found a total of 40 single nucleotide polymorphisms and 8
      insertion/deletion polymorphisms. No coding variants were identified in any of
      the three genes. Nine polymorphisms in IDE and four polymorphisms in KIF11
      situated in conserved regions or near coding exons were subsequently genotyped in
      a set of AD cases and controls. Two markers in KIF11 yielded borderline
      significant results in the ApoE4 non-carrier subgroup, but the results were
      otherwise not significant in this small set of samples. This study of multiple
      new markers in the region will facilitate further association studies in this
      important AD region.

PMID- 15858822
TI  - Relationship of serotonin transporter gene polymorphisms and haplotypes to mRNA
      transcription.
AB  - The serotonin transporter (5HTT; chromosomal location 17q12) is an important
      regulator of serotonergic neurotransmission and is the site of action for a
      number of antidepressant medications. Sequence variation at a VNTR known as the
      5HTTLPR, which is 1.4 kb upstream of the translation start of 5HTT, has been
      associated in some studies with increased vulnerability to depression,
      neuroticism, and autism. Support for these clinical observations has included
      laboratory findings that 5HTTLPR variation is associated with changes in 5HTT
      gene translation. We re-examined these earlier laboratory findings by directly
      measuring 5HTT mRNA levels and genotyping four loci spanning the 5HTT gene using
      RNA and DNA prepared from 85 independent lymphoblast cell lines. Using this data,
      haplotypes were inferred and the resulting single point and haplotypes data
      analyzed by univariate and regression analyses. Consistent with the original
      findings, we found a significant effect of the 5HTTLPR on mRNA production. In
      contrast to previous reports, the effect on 5HTT mRNA production appeared to be
      mediated through an additive, not dominant, mechanism. Neither genotype nor
      haplotype at three other 5HTT loci were associated with alterations in mRNA
      production, although the small number of samples homozygous for the three most
      common haplotypes limits these findings. We conclude that further examination of
      the role of 5HTT sequence variation in regulating 5HTT mRNA production is
      warranted.

PMID- 15858823
TI  - Germline mutations and polymorphisms in the NFKBIA gene in Hodgkin lymphoma.
AB  - Somatic inactivation of NFKBIA, the gene encoding IkappaBalpha, is a frequent
      occurrence in the malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin
      lymphoma (HL). Impairment of IkappaBalpha function results in deregulated NF
      kappaB activity, a characteristic of HRS cells. The molecular basis for familial
      HL, which accounts for approximately 4% of all HL cases, is unclear. To date,
      familial HL cases have not been evaluated for germline NFKBIA mutations. We
      screened the entire NFKBIA gene in 8 individuals with familial HL but found no
      mutations in the coding region or promoter sequences. We identified the first
      germline NFKBIA missense mutation in a patient with presumed sporadic HL. The
      frequency of 4 polymorphisms within the NFKBIA gene and promoter region was
      investigated in a series of HL and control samples; no significant differences
      emerged but a novel polymorphism was identified in the promoter region. Overall,
      our results suggest that germline mutations of NFKBIA are not a significant cause
      of familial aggregation of HL but may contribute to inherited susceptibility to
      HL.

PMID- 15858825
TI  - Structure-breaking effects of solvated Rb(I) in dilute aqueous solution--an ab
      initio QM/MM MD approach.
AB  - Structural properties of the hydrated Rb(I) ion have been investigated by ab
      initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD)
      simulations at the double-zeta HF quantum mechanical level. The first shell
      coordination number was found to be 7.1, and several other structural parameters
      such as angular distribution functions, radial distribution functions and tilt-
      and theta-angle distributions allowed the full characterization of the hydration
      structure of the Rb(I) ion in dilute aqueous solution. Velocity autocorrelation
      functions were used to calculate librational and vibrational motions, ion-ligand
      motions, as well as reorientation times. Different dynamical parameters such as
      water reorientation, mean ligand residence time, the number of ligand exchange
      processes, and rate constants were also analyzed. The mean ligand residence time
      for the first shell was determined as tau = 2.0 ps.

PMID- 15858824
TI  - Psychological distress in spouses of men treated for early-stage prostate
      carcinoma.
AB  - BACKGROUND: The authors examined levels and predictors of psychological distress
      in the wives of men treated for early-stage prostate carcinoma (PCa). METHODS:
      Patients with PCa (N = 165) and spouses were interviewed to assess general and
      cancer-specific distress. Social and intrapersonal factors of spouses as well as
      clinical characteristics and quality of life of patients were assessed as
      potential predictors of spouses' distress. RESULTS: Spouses reported more cancer
      specific distress than did patients (P < 0.001), but did not differ from patients
      in general distress. Several spouse-reported factors predicted higher spouses'
      distress, including less education (P < 0.005), worse marriage quality and less
      social support (Ps < 0.005), more negative social interaction with the patient
      (Ps < 0.001), lower self-esteem (Ps < 0.001), less positive coping (Ps < 0.005),
      searching for meaning (P < 0.001), not finding meaning (P < 0.005), and greater
      illness uncertainty (Ps < 0.001). Patients' bowel function and mental health also
      predicted greater spouses' distress (Ps < 0.005). CONCLUSIONS: The findings
      indicated that overall distress in spouses of early-stage patients with PCa was
      modest, and it was more likely to be predicted by psychosocial than medical
      factors.

PMID- 15858826
TI  - Localization of transient receptor potential ion channels in primary and motile
      cilia of the female murine reproductive organs.
AB  - We have examined the subcellular localization of transient receptor potential
      (TRP) ion channels and the potential sensory role of cilia in murine female
      reproductive organs using confocal laser scanning microscopy analysis on ovary
      and oviduct tissue sections as well as on primary cultures of follicular
      granulosa cells. We show that the Ca2+ permeable cation channel, polycystin-2, as
      well as polycystin-1, a receptor that forms a functional protein complex with
      polycystin 2, distinctively localize to primary cilia emerging from granulosa
      cells of antral follicles in vivo and in vitro. Both polycystins are localized to
      motile oviduct cilia and this localization is greatly increased upon ovulatory
      gonadotropic stimulation. Further, the Ca2+ permeable cation channel, TRP
      vaniloid 4 (TRPV4), localizes to a sub-population of motile cilia on the
      epithelial cells of the ampulla and isthmus with high intensity in proximal
      invaginations of the epithelial folds. These observations are the first to
      demonstrate ciliary localization of TRP ion channels and their possible receptor
      function in the female reproductive organs. We suggest that polycystins 1 and 2
      play an important role in granulosa cell differentiation and in development and
      maturation of ovarian follicles. In the oviduct both TRPV4 and polycystins could
      be important in relaying physiochemical changes in the oviduct upon ovulation.

PMID- 15858827
TI  - Efficient charge assignment and back interpolation in multigrid methods for
      molecular dynamics.
AB  - The assignment of atomic charges to a regular computational grid and the
      interpolation of forces from the grid back to the original atomic positions are
      crucial steps in a multigrid approach to the calculation of molecular forces. For
      purposes of grid assignment, atomic charges are modeled as truncated Gaussian
      distributions. The charge assignment and back interpolation methods are currently
      bottlenecks, and take up to one-third the execution time of the multigrid method
      each. Here, we propose alternative approaches to both charge assignment and back
      interpolation where convolution is used both to map Gaussian representations of
      atomic charges onto the grid and to map the forces computed at grid points back
      to atomic positions. These approaches achieve the same force accuracy with
      reduced run time. The proposed charge assignment and back interpolation methods
      scale better than baseline multigrid computations with both problem size and
      number of processors.

PMID- 15858828
TI  - Adaptive approach for nonlinear sensitivity analysis of reaction kinetics.
AB  - We present a unified approach for linear and nonlinear sensitivity analysis for
      models of reaction kinetics that are stated in terms of systems of ordinary
      differential equations (ODEs). The approach is based on the reformulation of the
      ODE problem as a density transport problem described by a Fokker-Planck equation.
      The resulting multidimensional partial differential equation is herein solved by
      extending the TRAIL algorithm originally introduced by Horenko and Weiser in the
      context of molecular dynamics (J. Comp. Chem. 2003, 24, 1921) and discussed it in
      comparison with Monte Carlo techniques. The extended TRAIL approach is fully
      adaptive and easily allows to study the influence of nonlinear dynamical effects.
      We illustrate the scheme in application to an enzyme-substrate model problem for
      sensitivity analysis w.r.t. to initial concentrations and parameter values.

PMID- 15858829
TI  - fMRI-constrained MEG source imaging and consideration of fMRI invisible sources.
AB  - Recent studies on multimodal brain source imaging have shown that the use of
      functional MRI (fMRI) prior information could enhance spatial resolution of
      magnetoencephalography (MEG), while MEG could compensate poor temporal resolution
      of fMRI. This article deals with a multimodal imaging method, which combines fMRI
      and MEG for enhancing both spatial and temporal resolutions. Recent studies on
      the combination of fMRI and MEG have suggested that the fMRI prior information
      could be very easily implemented by just giving different weighting factors to
      the diagonal terms of source covariance matrix in linear inverse operator. We
      applied the fMRI constrained imaging method to several simulation data and
      experimental data (Japanese language lexical judgment experiment), and found that
      some MEG sources may be eliminated by the introduction of the fMRI weighting and
      the eliminated sources may affect source estimation in fMRI activation regions.
      In this article, in order to check whether the eliminated sources were fMRI
      invisible ones or just spurious ones, we placed small numbers of regional sources
      (rotating dipoles) around all possible activation regions and investigated their
      temporal changes. By investigating the results carefully, we could evaluate
      whether the missed sources were real or not.

PMID- 15858830
TI  - Chiroptical properties of cation complexes of chiral phenazino-18-crown-6 ether
      type hosts.
AB  - Herein we report CD spectroscopic studies on complexes of (R,R)-dimethyl-, (R,R)
      diisobutyl-, and (S,S)-di-sec-butyl-phenazino-18-crown-6 ligands (Scheme 1) with
      selected alkali (Na+, K+), alkaline earth (Mg2+, Ca2+), and transition-metal
      (Ag+, Zn2+, Ni2+, Cd2+, Pb2+) cations. The complexation was monitored in the 300-
      to 240-nm region of the CD spectra comprising mainly the 1Bb band of the
      heteroaromatic subunit. The CD spectra of the complexes showed an unexpected
      diversity. In the most characteristic 1Bb spectral region, the number, position,
      and intensity of band(s) depend not only on the heteroaromatic subunit and the
      size of the substituents but also on the diameter, ion strength, and coordination
      geometry of the cation. The appearance of two weak 1Bb CD bands (type-I spectra)
      with the sign pattern of the host is an indication of two complexes of comparable
      stability. The "type-II" spectra differ from that of the host in the number, sign
      pattern, and intensity of the bands. Complexes of transition-metal cations
      generally show CD spectra with more intense bands. The CD spectra of complexes of
      (S,S)-di-sec-butyl-phenazino-18-crown-6 ligand with Na+, K+, and Pb2+ (type III)
      strongly suggest exciton coupling caused by the closeness of the heteroaromatic
      rings of two 1:1 complex molecules.

PMID- 15858831
TI  - Ventricle and outflow tract of the African lungfish Protopterus dolloi.
AB  - We report a morphologic study of the heart ventricle and outflow tract of the
      African lungfish Protopterus dolloi. The ventricle is saccular and appears
      attached to the anterior pericardial wall by a thick tendon. An incomplete septum
      divides the ventricle into two chambers. Both the free ventricular wall and the
      incomplete ventricular septum are entirely trabeculated. Only a thin rim of
      myocardium separates the trabecular system from the subepicardial space. The
      outflow tract consists of proximal, middle, and distal portions, separated by two
      flexures, proximal and distal. The proximal outflow tract portion is endowed with
      a layer of compact, well-vascularized myocardium. This portion is homologous to
      the conus arteriosus observed in the heart of most vertebrates. The middle and
      distal outflow tract portions are arterial-like, thus being homologous to the
      bulbus arteriosus. However, the separation between the muscular and arterial
      portions of the outflow tract is not complete in the lungfish. A thin layer of
      myocardium covers the arterial tissue, and a thin layer of elastic tissue
      underlies the conus myocardium. Two unequal ridges composed of loose connective
      tissue, the spiral and bulbar folds, run the length of the outflow tract. They
      form an incomplete division of the outflow tract, but fuse at the distal end. The
      two folds are covered by endocardium and contain collagen, elastin, and
      fibroblast-like cells. They appear to be homologous to the dextro-dorsal and
      sinistro-ventral ridges observed during the development of the avian and
      mammalian heart. Two to three rows of vestigial arterial-like valves appear in
      the dorsal and ventral aspects of the conus. These valves are unlikely to have a
      functional role. The possible functional significance of the "gubernaculum
      cordis," the thick tendon extending between the anterior ventricular surface and
      the pericardium, is discussed.

PMID- 15858832
TI  - Intermittent cortical stimulation evokes sensitization to cocaine and enduring
      changes in matrix and striosome neuron responsiveness.
AB  - Both the behavioral sensitization syndrome and the changes in the responsiveness
      of striatal neurons evoked by chronic cocaine exposure may be linked to enhanced
      neocortical activity, yet a direct demonstration of the effects of cortical
      stimulation on these parameters is lacking. We have found that repeated
      stimulation of the rat prelimbic cortex with picrotoxin (0.25 microg/0.25 microl,
      five injections on alternate days followed by 7-day withdrawal) contributed to
      increase c-Fos protein expression in the striosomes of the dorsolateral striatum,
      while producing the opposite effect in the matrix compartment, after a single
      exposure to cocaine (25 mg/kg). Moreover, rats exposed to cortical stimulation
      showed decreased locomotor activation but enhanced stereotypy following acute
      cocaine treatment. Thus, pulsatile stimulation of the prelimbic cortex
      facilitated modifications in striatal activity typically produced by chronic
      cocaine treatment and sensitized drug-naive animals to acute cocaine challenge.
      These results suggest that enhanced activation of the prelimbic cortex may
      contribute to the long-term adaptations induced by cocaine on neural activity and
      behavior.

PMID- 15858833
TI  - Ketamine and amphetamine both enhance synaptic transmission in the amygdala
      nucleus accumbens pathway but with different time-courses.
AB  - Excitatory glutamatergic fibers from limbic structures, such as the hippocampus
      and the basolateral amygdala, are known to converge on the same neurons in the
      nucleus accumbens. We have recently shown that ketamine, at a dose (25 mg/kg)
      that produces psychosis-like behaviors in rats, decreases glutamatergic
      transmission between the hippocampus and the nucleus accumbens. Here we
      investigated whether ketamine also affects glutamatergic transmission between the
      basolateral amygdala and the nucleus accumbens. We also studied the effects of
      amphetamine (1.5 mg/kg), known to evoke psychosis-like behaviors in rats. We
      found that each drug produced a long-lasting (at least 30 min) potentiation of
      synaptic efficacy in the projection from the basolateral amygdala to the nucleus
      accumbens. However, while this synaptic potentiation developed shortly after
      ketamine injection (within 4 min), it occurred after a 30-min delay in rats
      injected with amphetamine. These data reveal, in freely behaving rats, that
      ketamine has a more rapid and powerful effect on projection targets of the
      basolateral amygdala than does amphetamine.

PMID- 15858834
TI  - Inhibition of neuronal nitric oxide synthase attenuates the development of
      morphine tolerance in rats.
AB  - Our previous results have shown the involvement of nitric oxide in acute opioid
      desensitization of mu-opioid receptors in vitro. In the present study, we
      investigated the effect of repeated administration of 7-nitroindazole (7-NI; 30
      mg/kg/12 h, i.p., 3 days), an inhibitor of neuronal nitric oxide synthase in
      vivo, on mu-opioid receptor tolerance induced by subchronic treatment with
      morphine in rats. The inhibitory effect of the opioid agonist Met5-enkephalin
      (ME) on the cell firing rate was evaluated by single-unit extracellular
      recordings of noradrenergic neurons in the locus coeruleus from brain slices, and
      the antinociceptive effect of morphine was measured by tail-flick techniques. In
      morphine-treated animals, concentration-effect curves for ME in the locus
      coeruleus were shifted by 5-fold to the right as compared to those in sham
      treated animals, which confirmed the induction of mu-opioid receptor tolerance.
      However, tolerance to ME in morphine-treated rats was fully prevented by co
      administration of 7-NI when compared to the vehicle-morphine group. Likewise, the
      antinociceptive effect of morphine was reduced in morphine-treated animals as
      compared to the sham group, whereas the antinociceptive tolerance was partially
      prevented by co-administration of 7-NI in morphine-treated rats (when compared to
      the vehicle-morphine group). Finally, 7-NI administration in sham-treated rats
      failed to change the effect induced by ME on the locus coeruleus or by morphine
      in the tail-flick test as compared to vehicle groups. These results demonstrate
      that subchronic administration of a neuronal inhibitor of nitric oxide synthase
      attenuates the development of morphine tolerance to the cellular and analgesic
      effects of mu-opioid receptor agonists.

PMID- 15858835
TI  - Ultrastructural alterations in hippocampal mossy fiber synapses in schizophrenia:
      a postmortem morphometric study.
AB  - Synapses formed between mossy fibers, the axons of hippocampal dentate granular
      cells, and the dendrites of CA3 pyramidal neurons are important links within the
      trisynaptic circuitry. Abnormalities in this circuitry are associated with the
      failure of schizophrenics to integrate affective experience with higher cognitive
      function, and with disturbances in memory and spatial learning processes. The
      abnormalities include reduced size and altered dendritic arborization of CA3
      pyramidal neurons. In addition, decreased expression and binding activity of
      glutamate receptors have been reported, predominantly in the CA3 region of the
      hippocampus. These findings suggest that there are disturbed neuronal processes
      and connections in the hippocampus of schizophrenics. An electron microscope
      morphometric study of synaptic contacts between mossy fiber axon terminals (MFT)
      and branched dendritic spines of pyramidal neurons in stratum lucidum of the CA3
      region of the hippocampus was performed in 10 normal controls and 9 age-matched
      chronic schizophrenics (postmortem delay 3-9 h). Schizophrenic cases with
      predominantly positive symptoms had a significantly reduced volume fraction of
      spines (-35%, P < 0.05), total number of invaginated spines (-47%, P < 0.01), and
      number of spines forming synapses (-32%, P < 0.05) per MFT compared with the
      control group. No effects of postmortem delay, age, duration of disease, or
      neuroleptic exposure were found. These data may reflect decreased efficacy of
      mossy fiber synapses in the CA3 hippocampal region in schizophrenics with
      predominantly positive symptoms. These data are in line with the
      neurodevelopmental hypothesis of schizophrenia.

PMID- 15858836
TI  - Expression and distribution of kinin B1 receptor in the rat brain and alterations
      induced by diabetes in the model of streptozotocin.
AB  - A role for kinin B1 receptors was suggested in the spinal cord and peripheral
      organs of streptozotocin (STZ)-diabetic rats. The present study aims at
      determining whether B1 receptors are also induced and over-expressed in the brain
      of STZ-rats at 2, 7, and 21 days post-treatment. This was addressed by in situ
      hybridization using the [35S]-UTPalphaS-labeled riboprobe and by in vitro
      autoradiography with the radioligand [125I]-HPP-des-Arg10-Hoe 140. In control
      rats, B1 receptor mRNA was found widely distributed in many brain regions. Low
      mRNA levels were found in thalamus and hypothalamus (7-12 nCi/g) while high mRNA
      signals were detected in cortical regions and hippocampus (18-29 nCi/g). In
      diabetic rats, B1 receptor mRNA was markedly increased in hippocampus,
      temporal/parietal cortices and amygdala at 2 and 7 days (+88 to +150%). Low
      densities of B1 receptor binding sites were detected in all analyzed regions in
      control rats (0.18-0.37 fmol/mg tissue). In diabetic rats, B1 receptor binding
      sites were significantly increased in hippocampus, amygdala, temporal/parietal,
      and perhinal/piriform cortices (+ 55 to + 165 %) at 7 days only. Results
      highlight an early but transient and reversible up-regulation of B1 receptors in
      specific brain regions of STZ-diabetic rats. This may offer the advantage of
      reducing putative central side effects with B1 receptor antagonists if used for
      the treatment of diabetic complications in the periphery.

PMID- 15858837
TI  - Mice lacking the adenosine A1 receptor have normal spatial learning and
      plasticity in the CA1 region of the hippocampus, but they habituate more slowly.
AB  - Using mice with a targeted disruption of the adenosine A1 receptor (A1R), we
      examined the role of A1Rs in hippocampal long-term potentiation (LTP), long-term
      depression (LTD), and memory formation. Recordings from the Shaffer collateral
      CA1 pathway of hippocampal slices from adult mice showed no differences between
      theta burst and tetanic stimulation-induced LTP in adenosine A1 receptor knockout
      (A1R-/-), heterozygote (A1R+/-), and wildtype (A1R+/+) mice. However, paired
      pulse facilitation was impaired significantly in A1R-/- slices as compared to
      A1R+/+ slices. LTD in the CA1 region was unaffected by the genetic manipulation.
      The three genotypes showed similar memory acquisition patterns when assessed for
      spatial reference and working memory in the Morris water maze tasks at 9 months
      of age. However, 10 months later A1R-/- mice showed some deficits in the 6-arm
      radial tunnel maze test. The latter appeared, however, not due to memory deficits
      but to decreased habituation to the test environment. Taken together, we observe
      normal spatial learning and memory and hippocampal CA1 synaptic plasticity in
      adult adenosine A1R knockout mice, but find modifications in arousal-related
      processes, including habituation, in this knockout model.

PMID- 15858838
TI  - Intrastriatal dopamine D1 receptor agonist-mediated motor behavior is reduced by
      local neurokinin 1 receptor antagonism.
AB  - Recent evidence suggests that striatal neurokinin receptors modulate dopamine
      (DA)-induced motor behaviors. To further examine this, we studied the effects of
      intrastriatal neurokinin 1 receptor (NK1R) antagonism on motor behaviors induced
      by direct infusion of the full DA D1 receptor agonist SKF 82958. Adult male
      Sprague-Dawley rats received bilateral intrastriatal 0.8-mul infusions of the
      NK1R receptor antagonist LY 306,740 (0, 27, or 54 nmol/side) followed by
      intrastriatal infusions of SKF 82958 (0 or 24 nmol/side) into the dorsal
      striatum. Following each infusion, rats were placed into automated activity
      monitors for the quantification of horizontal activity, total distance traveled,
      movement bouts, and stereotypy counts. As expected, SKF 82958 increased motor
      activity on all behavioral measures. More importantly, whereas 27 nmol was
      without effect, prior infusion of 54 nmol LY 306,740 significantly reduced most
      aspects of behavior. The results of this study suggest that functional NK1Rs
      within the striatum play a permissive role in the motor behaviors induced by D1R
      stimulation.

PMID- 15858840
TI  - Pharmacokinetic study of methotrexate following intra-articular injection of
      methotrexate loaded poly(L-lactic acid) microspheres in rabbits.
AB  - The pharmacokinetics and tissue distribution of methotrexate (MTX) were
      investigated following intra-articular injection of either MTX solution or
      controlled release MTX loaded microspheres in healthy rabbit joints. MTX solution
      or MTX loaded microspheres (size 30-100 mum) (10 mg MTX) was injected into the
      right knee joint cavity of rabbits. Blood samples were taken at predetermined
      times from the jugular vein. Urine samples were also collected over time periods
      up to 24 h. The major organs and synovial tissues were removed for analysis 6 and
      24 h post-injection (n = 4). MTX and 7-OH-MTX concentrations in the plasma and
      major organs were determined by HPLC. The MTX plasma area under the concentration
      time curve (AUC) for rabbits injected with MTX solution was seven fold higher
      than that of the rabbits injected with MTX microspheres, while t(1/2) and mean
      residence time (MRT) were not significantly different between two treatment
      groups. Four fold more MTX was excreted in the urine from rabbits injected with
      MTX solution compared to those injected with MTX loaded microspheres 24 h
      following intra-articular injection. The concentration of MTX in the synovial
      tissues following intra-articular injection was significantly higher in the
      rabbits injected with microspheres than in the rabbits injected with MTX
      solution. MTX solution was rapidly cleared from the joint cavity while MTX
      encapsulated microspheres retained MTX in the joint cavity.

PMID- 15858839
TI  - Acute administration of SB-277011A, NGB 2904, or BP 897 inhibits cocaine cue
      induced reinstatement of drug-seeking behavior in rats: role of dopamine D3
      receptors.
AB  - Recent studies have shown that the novel dopamine (DA) D3 receptor antagonists SB
      277011A and NGB 2904 inhibit cocaine- and/or stress-induced reinstatement of drug
      seeking behavior. The present study sought to determine if SB-277011A, NGB 2904,
      or BP-897 (a mixed D3 agonist/antagonist) similarly inhibit cocaine-associated
      cue-induced reinstatement of drug-seeking behavior. Long-Evans rats were allowed
      to self-administer cocaine. Each cocaine infusion was paired with discrete
      conditioned cue-light and tone. Subsequently, drug-seeking (i.e., lever-pressing)
      behavior was extinguished in the absence of cocaine and cocaine-associated cues.
      Rats were then tested for cue-induced reinstatement of drug-seeking. We found
      that cocaine-associated cues evoked robust reinstatement of lever-pressing. Acute
      intraperitoneal (i.p.) administration of SB-277011A (6, 12, or 24 mg/kg) produced
      a dose-dependent inhibition of cue-induced reinstatement of drug-seeking behavior
      by 35, 65, and 85%, respectively, compared to vehicle-treated animals. Acute i.p.
      administration of NGB 2904 (0.1, 1.0, or 5.0 mg/kg) produced a 45, 30, and 70%
      inhibition of cue-induced reinstatement, respectively, compared to vehicle
      treated animals. Acute i.p. administration of either 0.1 or 1 mg/kg of BP 897 did
      not produce a significant effect on cue-induced reinstatement, whereas a dose of
      3 mg/kg produced a 70% inhibition of cue-induced reinstatement. These findings,
      combined with previous data, suggest that DA D3 receptor antagonism may underlie
      the inhibitory effects of SB-277011A and NGB 2904 on cocaine cue-induced
      reinstatement, while the effects of BP 897 may involve D3 and non-D3 receptor
      mechanisms.

PMID- 15858841
TI  - PEGylation of yeast cytosine deaminase for pretargeting.
AB  - Yeast cytosine deaminase (yCD) was cloned, expressed, and purified by affinity
      chromatography. We have characterized the products resulting from covalent
      attachment of 2-4 PEG chains on yCD and determined the major and minor isomers
      for each respective conjugate. The results show that for non-covalently
      associated homodimers, it is possible to characterize and deduce PEGylation
      levels on individual subunits through the concurrent use of size exclusion
      chromatography (SEC), MALDI-TOF MS, and SDS-PAGE gels. The results also show that
      contrary to what we expected, attaching more than two PEG chains to yCD decreased
      its stability. Enzymatic activity studies revealed that the fusion of an N
      terminus purification tag on yCD has no significant effect on 5-fluorocytosine or
      cytosine affinity, with apparent turnover rates remaining within 10(5) M(-1) . s(
      1). Stability studies at 37 degrees C revealed that t1/2 = 8-9 h for yCD and
      2mPEG(5K)-yCD, whereas for 3-, 4mPEG(5K)-yCD and yCD/BSA, t(1/2) < 2 h.
      Incubation of BSA with yCD also decreased enzyme stability over prolonged
      incubation at 37 degrees C. This finding is important if yCD is to be used in a
      pretargeting strategy.

PMID- 15858842
TI  - Studies on the crystallinity of a pharmaceutical development drug substance.
AB  - The crystallinity and amorphous content of a micronized pharmaceutical
      development drug substance have been independently determined. An evaluation of
      different techniques for this purpose has been carried out, and it was found that
      solid-state nuclear magnetic resonance (ss NMR) and X-ray powder diffraction
      (XRPD) were suitable for the former and latter, respectively. The baseline
      intensities of X-ray powder diffractograms, associated with the amorphous
      component of the sample, have been used to detect levels of non-crystalline
      material greater than 5%w/w with an absolute accuracy of +/-3%. ss NMR has been
      employed to quantify crystalline defects at levels of greater than 3%w/w with an
      estimated uncertainty of +/-2%. It is proposed that such crystalline defects
      arise from molecular conformational differences that only have a small effect on
      crystal lattice parameters and, by implication, only have small effects on X-ray
      powder diffractograms. In both cases the techniques are shown to be highly
      reproducible and require minimal sample preparation. Excellent linearity is
      demonstrated for the determination of amorphous material using prepared
      standards. The present account describes the choice of analytical method, method
      validation and the results obtained for typical samples of drug substance. It is
      demonstrated that solid-state NMR should be used as a complementary technique
      with respect to XRPD for studying crystallinity.

PMID- 15858843
TI  - Statistical analysis of differences in the Raman spectra of polymorphs.
AB  - Raman spectroscopy is a useful tool for identifying polymorphs of pharmaceutical
      compounds. One limitation of the technique is that the small differences in Raman
      spectra require confirmation of polymorphs by other methods. Fourteen compounds,
      both commercial and proprietary pharmaceutical compounds and their polymorphs,
      were analyzed by Raman microscopy. By using descriptive statistics and analysis
      of variance (ANOVA), several methods are proposed that provide an approach for
      comparing the spectra of suspected polymorphs. Because it is difficult to
      determine the exact amount that a peak may shift before two forms should be
      considered different; a guideline of a shift greater than 1.6/cm(-1) is proposed.
      A standard ANOVA analysis is used to compare individual peaks both within and
      between polymorphs, as well as an alternative method that proposes the use of a
      total ANOVA table that considers the entire spectrum. Both methods have their
      advantages and disadvantages, but they provide a starting point for the
      comparison of a large number of spectra, and effectively differentiate between
      polymorphs of a given compound. The method accurately identified true polymorphs
      in all cases, but showed a bias towards misidentifying some samples as polymorphs
      when they were in fact the same form. This bias was not significant and even in
      these situations, the magnitude of the calculated F values was a useful indicator
      of whether the result was a false positive or not.

PMID- 15858844
TI  - Role of organic anion transporting polypeptide 2 in pharmacokinetics of digoxin
      and beta-methyldigoxin in rats.
AB  - Recently, we found that potent P-glycoprotein (P-gp) inhibitors, such as
      verapamil and cyclosporin A, markedly modulated the pharmacokinetics of digoxin
      in rats, whereas they did not affect beta-methyldigoxin pharmacokinetics
      significantly. Digoxin is also a substrate of rat organic anion transporting
      polypeptide 2 (Oatp2). Here, we compared the magnitude of Oatp2-mediated drug
      interaction of digoxin and beta-methyldigoxin using amiodarone as an Oatp2
      inhibitor in rats. Amiodarone (20 mg/kg) given intravenously significantly
      increased plasma levels and decreased biliary excretion, liver distribution, and
      intestinal distribution of digoxin administered intravenously at a dose of 10
      mug/kg. Amiodarone also significantly decreased biliary excretion and liver
      distribution of beta-methyldigoxin, but the change in plasma levels of beta
      methyldigoxin was quite small. These findings may give a clue in selecting these
      cardiac glycosides in clinical pharmacotherapy for patients receiving multiple
      drugs towards escape from Oatp2-mediated drug interactions.

PMID- 15858845
TI  - Interaction of clonixin with EPC liposomes used as membrane models.
AB  - In this work, an overall analysis of clonixin interaction with liposomes was
      achieved using different techniques, which allowed the evaluation of the change
      in different membrane's characteristics as well as the possible location of the
      drug in the membrane. Clonixin acidity constants were obtained and the values are
      5.5 +/- 0.08 and 2.2 +/- 0.04. Clonixin partition coefficient (K(p)) between
      liposomes and water was also determined using derivative spectrophotometry,
      fluorescence quenching, and zeta-potential (zeta-potential). These three
      techniques yielded similar results. zeta-potential measurements were performed
      and an increase of the membrane negative charge with an increase of drug
      concentration was observed. Drug location within the bilayer was performed by
      fluorescence quenching using a set of n-(9-anthroyloxy) fatty acid probes (n = 2,
      6, 9, and 12). The fluorescence intensity of all probes was quenched by the drug.
      This effect is more noticeable for the outer located probe, indicating that the
      drug is positioning in the external part of the membrane. These same probes were
      used for steady-state anisotropy measurements to determine the perturbation in
      membrane structure induced by clonixin. Clonixin increased membrane fluidity in a
      concentration dependent manner, with the highest perturbation occurring nearby
      the 2-AS probe, closely located to the bilayer surface.

PMID- 15858846
TI  - Application of ultrasonic shear rheometer to characterize rheological properties
      of high protein concentration solutions at microliter volume.
AB  - The purpose of this work was to conduct preliminary rheological analysis on high
      protein concentration solutions by using the technique of ultrasonic shear
      rheometry at megahertz frequencies. The work was aimed at establishing the
      viability of the technique for analyzing protein solution rheology as well as
      obtaining an initial understanding of the effect of solution conditions on
      solution rheology of a model protein. Bovine serum albumin (BSA) was used for
      this study, and rheological analysis was conducted at 20 microL sample volume
      between pH 2.0 and 9.0 at different ionic strengths at 25 degrees C using 5 and
      10 MHz quartz crystals. Significant differences in storage modulus among
      solutions at pH 5.0, 7.0, and 9.0 could only be detected at 10 MHz, and the
      errors associated with measurements were smaller as compared to those at 5 MHz
      for all the solutions studied. Solutions at pH 2.0 and 3.0 showed a time
      dependent change in solution rheology. For solutions at pH 5.0, 7.0, and 9.0,
      which did not show time dependence in solution rheology, loss modulus data at
      lower concentrations correlated well with the dilute solution data in the
      literature. At higher concentrations, pH 5.0 solutions exhibited a higher loss
      modulus than pH 7.0 and pH 9.0 solutions. Storage modulus decreased with
      increasing ionic strength, unlike loss modulus, which did not show any change,
      except at pI of protein when no effect was observed. The results show the
      potential of high frequency rheometry for analyzing subtle differences in
      rheology of pharmaceutically relevant protein solutions at microliter volume.

PMID- 15858847
TI  - Nuclear receptors and drug disposition gene regulation.
AB  - In this minireview, the role of various nuclear receptors and transcription
      factors in the expression of drug disposition genes is summarized. Specifically,
      the molecular aspects and functional impact of the aryl hydrocarbon receptor
      (AhR), nuclear factor-E2 p45-related factor 2 (N(r)f2), hepatocyte nuclear factor
      1alpha (HNF1alpha), constitutive androstane receptor (LAR), pregnane X receptor
      (PXR), farnesoid X receptor (FXR), peroxisome proliferator-activated receptor
      alpha (PPAR(alpha)), hepatocyte nuclear factor 4alpha (HNF4alpha), vitamin D
      receptor (VDR), liver receptor homolog 1 (LRH1), liver X receptor (LXR(alpha)),
      small heterodimer partner-1 (SHP-1), and glucocorticoid receptor (GR) on gene
      expression are detailed. Finally, we discuss some current topics and themes in
      nuclear receptor-mediated regulation of drug metabolizing enzymes and drug
      transporters.

PMID- 15858848
TI  - Effects of Tween 20 and Tween 80 on the stability of Albutropin during agitation.
AB  - The objectives of this work were to determine the effects of nonionic surfactants
      (Tween 20 and Tween 80) on agitation-induced aggregation of the recombinant
      fusion protein, Albutropintrade mark (human growth hormone genetically fused to
      human albumin), and to characterize the binding interactions between the
      surfactants and the protein. Knowing the binding stoichiometry would allow a
      rational choice of surfactant concentration to protect the protein from surface
      induced aggregation. Fluorescence spectroscopy and isothermal titration
      calorimetry (ITC) were employed to study Albutropin surfactant binding.
      Albutropin was agitated at 25 +/- 2 degrees C to induce aggregation, and samples
      were taken during a 96-h incubation. Size-exclusion chromatography (SEC-HPLC)
      (HPLC, high-performance liquid chromatography) was used to detect and quantify
      the extent of protein aggregation. The effect of surfactants on the protein's
      free energy of unfolding was determined using guanidine HCl as a denaturant.
      Tween 20 and Tween 80 had saturable binding to Albutropin with a molar binding
      stoichiometry of 10:1 and 9:1 (surfactant:protein), respectively. Binding of the
      surfactants to Albutropin increased the free energy of unfolding by over 1 and
      0.6 kcal/mol, respectively. In protein samples that were agitated in the absence
      of surfactant, soluble aggregates were detected within 24 h, and there was almost
      complete loss of monomer to soluble aggregates by the end of the 96-h experiment.
      At the molar binding stoichiometry, Tween 20 and Tween 80 prevented the formation
      of soluble aggregates, even though the concentrations of surfactants were well
      below their critical micelle concentrations (CMC). Tween 20 and Tween 80
      protected Albutropin against agitation-induced aggregation, even at
      concentrations below the CMC. Equilibrium unfolding data indicate that Tween
      confer protection by increasing the free energy of unfolding of Albutropin.

PMID- 15858849
TI  - Post-thaw aging affects activity of lactate dehydrogenase.
AB  - Freeze-thawing is routinely used to study freezing-induced irreversible protein
      denaturation in the formulation characterization and development of lyophilized
      proteins. In most cases, the temperature profiles of the samples are not fully
      monitored during freeze-thawing and therefore, the sample thermal histories are
      largely unknown. The objective of this study was to develop experimental
      protocols for the study of isothermal protein degradation using a temperature
      step apparatus. Freeze-thaw experiments were performed at a freezing rate of 10
      degrees C/min and various thawing rates (0.5-3.3 degrees C/min) using a
      temperature-step apparatus. In our efforts to design validation studies, we
      encountered anomalies in the recovered enzyme activity data of an enzyme, lactate
      dehydrogenase at the end of freeze-thawing. The effect of thawing rate was
      studied to explain the variability in the data. In addition, post-thaw "aging" of
      freshly frozen and thawed samples was performed at 5 degrees C to reduce the
      variability in the recovered enzyme activity. Results from these experiments
      implicate the use of aging of dilute multimeric enzymes at the end of freeze
      thawing to control the variability in enzyme assays.

PMID- 15858850
TI  - Nasal drug administration: potential for targeted central nervous system
      delivery.
AB  - Nasal administration as a means of delivering therapeutic agents preferentially
      to the brain has gained significant recent interest. While some substrates appear
      to be delivered directly to the brain via this route, the mechanisms governing
      overall brain uptake and exposure remain unclear. Some substrates utilize the
      olfactory nerve tract and gain direct access to the brain, thus bypassing the
      blood-brain barrier (BBB). However, most agents of pharmacologic interest likely
      gain access to the brain via the olfactory epithelium, which represents a more
      direct route of uptake. While the traditional BBB is not present at the interface
      between nasal epithelium and brain, P-glycoprotein (and potentially other barrier
      transporters) is expressed at this interface. In addition, work in this
      laboratory has demonstrated that P-glycoprotein throughout the brain can be
      modulated with nasal administration of appropriate inhibitors. The potential for
      targeted central nervous system delivery via this route is discussed.

PMID- 15858851
TI  - Tissue distribution of basic drugs: accounting for enantiomeric, compound and
      regional differences amongst beta-blocking drugs in rat.
AB  - The purpose of this research was to identify the major factors controlling the
      distribution of beta-blockers (acebutolol, betaxolol, bisoprolol, metoprolol,
      oxprenolol, pindolol, propranolol and timolol) in rats, across tissues, compounds
      and enantiomers. Tissue distribution was assessed at steady state by infusing
      cassette doses of beta-blockers into the jugular vein via an indwelling catheter
      at a constant rate. Blood was sampled via an indwelling catheter in the carotid
      artery, and 12 tissues excised at the end of dose infusion (4 or 8 h). Drug
      concentrations were quantified using a novel chiral LC-MS method and the tissue
      to-plasma (Kp) and tissue-to-plasma water (Kpu) values were calculated for each
      tissue. Differences between Kp were observed between many enantiomeric pairs, and
      largely explained by enantiomeric differences in plasma protein binding. Across
      compounds, Kpu values were generally highest in lung and lowest in adipose, and
      were higher for the more lipophilic drugs betaxolol and propranolol. For any
      tissue, Kpu differences between the individual beta-blockers correlated well with
      the corresponding affinity for blood cells. For all compounds, regional tissue
      distribution correlated well with tissue acidic phospholipid concentrations, with
      phosphatidylserine appearing to have the strongest influence. This information
      may be used as the basis for predicting the tissue distribution of basic drugs.

PMID- 15858852
TI  - Application of NIR spectroscopy in polymorphic analysis: study of pseudo
      polymorphs stability.
AB  - The accelerated transformation of three azithromycin pseudo-polymorphs (viz. the
      anhydrous, monohydrate (MH), and dihydrate (DH) forms) at a high temperature and
      moisture level was examined by near infrared spectroscopy (NIRS). The most marked
      spectral differences between the pseudo-polymorphs occurred in the 1800-2200 nm
      region, which corresponds to the first overtone for water. The qualitative
      analysis of the NIR spectra for the pseudo-polymorphs following storage in a
      stove at 60 degrees C at 100% relative humidity for 60 days suggests that the
      crystalline forms (viz. the MH and DH) are stable, whereas the amorphous
      (anhydrous) form evolves to the DH. This was confirmed by determining the amounts
      of water and DH present in anhydrous azithromycin and the MH by use of partial
      least-squares regression (PLSR). The method used to quantify the DH in MH samples
      was developed and validated in accordance with the standards of the International
      Conference of Harmonization (ICH) and the European Medicines Agency (EMEA) with a
      view to its subsequent application by the pharmaceutical industry. The limits of
      detection (LD) and quantitation (LQ) for the DH in MH provided by the NIRS method
      were consistent with those obtained by X-ray diffraction (XRD) methodology. This
      testifies to the accuracy of the proposed method.

PMID- 15858854
TI  - Physiologically based pharmacokinetic modeling 1: predicting the tissue
      distribution of moderate-to-strong bases.
AB  - Tissue-to-plasma water partition coefficients (Kpu's) form an integral part of
      whole body physiologically based pharmacokinetic (WBPBPK) models. This research
      aims to improve the predictability of Kpu values for moderate-to-strong bases
      (pK(a) > or = 7), by developing a mechanistic equation that accommodates the
      unique electrostatic interactions of such drugs with tissue acidic phospholipids,
      where the affinity of this interaction is readily estimated from drug blood cell
      binding data. Additional model constituents are drug partitioning into neutral
      lipids and neutral phospholipids, and drug dissolution in tissue water. Major
      assumptions of this equation are that electrostatic interactions predominate,
      drugs distribute passively, and non-saturating conditions prevail. Resultant Kpu
      predictions for 28 moderate-to-strong bases were significantly more accurate than
      published equations with 89%, compared to 45%, of the predictions being within a
      factor of three of experimental values in rat adipose, bone, gut, heart, kidney,
      liver, muscle, pancreas, skin, spleen and thymus. Predictions in rat brain and
      lung were less accurate probably due to the involvement of additional processes
      not incorporated within the equation. This overall improvement in prediction
      should facilitate the further application of WBPBPK modeling, where time, cost
      and labor requirements associated with experimentally determining Kpu's have, to
      a large extent, deterred its application.

PMID- 15858853
TI  - Double-coated poly (butylcynanoacrylate) nanoparticulate delivery systems for
      brain targeting of dalargin via oral administration.
AB  - The aim of this study is to evaluate oral administration of poly
      (butylcyanoacrylate) nanoparticulate delivery systems (PBCA-NDSs), double-coated
      with Tween 80 and poly (ethylene) glycol (PEG) 20000 for brain delivery of
      hexapeptide dalargin, an anti-nociceptive peptide that does not cross blood-brain
      barrier (BBB) by itself. Studies have proven the brain uptake of Tween 80
      overcoated nanoparticles after intravenous administration, but studies for brain
      delivery of nanoparticles after oral administration had been limited due to
      reduced bioavailability of nanoparticles and extensive degradation of the peptide
      and/or nanoparticles by gastrointestinal enzymes. To address this problem,
      dalargin-loaded PBCA-NDS were successively double-coated with Tween 80 and PEG
      20000 in varied concentrations of up to 2% each. Measurement of in vivo central
      anti-nociceptive effect of dalargin along with a dose response curve was obtained
      by the tail flick test following the oral administration of PBCA-NDSs to mice.
      Results from the tail flick test indicated that significant dalargin-induced
      analgesia was observed from PBCA-NDSs with double-coating of Tween and PEG in
      comparison with single-coating of either Tween or PEG. Hence, it could be
      concluded that surface coated PBCA-NDS can be used successfully for brain
      targeting of dalargin or other peptides administered orally. However, further
      studies are required to elucidate the exact transport mechanism of PBCA-NDSs from
      gastrointestinal tract to brain.

PMID- 15858855
TI  - IPM/DOSS/water microemulsions as reactors for silver sulfadiazine nanocrystal
      synthesis.
AB  - The first goal of this work was the preparation of a water-in-oil microemulsion
      from components generally regarded as safe for use in humans. Stable formulations
      without need of a co-surfactant were prepared from isopropyl myristate (IPM),
      dioctyl sodium sulfosuccinate (DOSS), and water. A ternary phase diagram was
      prepared for the IPM/DOSS/water system. The IPM/DOSS/water microemulsions were
      characterized by conductivity and dynamic laser light scattering (DLS). The
      results obtained from conductivity experiments indicate conductivity values of
      less than 1 muS/cm and were consistent with the formation of w/o microemulsions.
      The DLS results showed that the emulsified water droplets had an average diameter
      range of 9.2 to 19.7 nm, depending on composition. Modulation of the droplet size
      is possible by varying the water to DOSS molar ratio and DOSS to IPM ratio. The
      second goal of this work was the preparation of silver sulfadiazine (AgSD)
      nanoparticles. It was hypothesized that two separate microemulsions containing
      dispersed aqueous droplets of either sodium sulfadiazine or silver nitrate would
      react when mixed. The DLS results are consistent with the successful formation of
      submicron AgSD crystals.

PMID- 15858856
TI  - The impact of pharmacologic and genetic knockout of P-glycoprotein on nelfinavir
      levels in the brain and other tissues in mice.
AB  - Insufficient concentrations of protease inhibitors such as nelfinavir may reduce
      the effectiveness of HIV dementia treatment. The efflux transporter mdr1 product
      P-glycoprotein (P-gp) has been demonstrated to play a role in limiting nelfinavir
      brain levels. The goal of this study was to compare the effect of GF120918 (10
      mg/kg, IV), a P-gp inhibitor, on intravenous nelfinavir (10 mg/kg) in vivo
      disposition and tissue penetration in P-gp-competent mdr1a/1b (+/+) mice versus P
      gp double knockout mdr1a/1b (-/-) mice. Intravenous administration with the P-gp
      inhibitor GF120918 to mdr1a/1b (+/+) mice increased nelfinavir concentrations
      over a range of 2.3- to 27-fold, whereas nelfinavir distribution in mdr1a/1b (-/
      ) mice was 2- to 16-fold higher than that in their wild counterparts. Nelfinavir
      levels after GF120918 coadministration were higher in the heart, liver, and
      kidneys than those detected with mdr1a/1b knockout mice. In contrast, mdr1a/1b
      knockout mice exhibited higher nelfinavir levels in the brain (16.1-fold vs. 8.9
      fold increase) and spleen (4.1-fold vs. 2.3-fold increase) compared to
      pharmacological inhibition with GF120918 in wild mice. Most notably, GF120918
      provided tissue-specific effects in mdr1a/1b knockout mice with enhanced (p <
      0.05) drug accumulation in the brain ( approximately 21-fold) and heart (3.3
      fold). Our results suggest mdr1a/1b-independant mechanisms may also contribute to
      nelfinavir tissue distribution in mice.

PMID- 15858857
TI  - Low molecular weight dextrans stabilize nonviral vectors during lyophilization at
      low osmolalities: concentrating suspensions by rehydration to reduced volumes.
AB  - Stabilization of nonviral vectors during freezing and drying requires formulation
      with protective excipients such that transfection rates and physical
      characteristics are maintained upon reconstitution. While many studies have
      demonstrated the ability of disaccharides (e.g., sucrose) to effectively protect
      nonviral vectors during lyophilization, the sucrose/DNA weight ratios required to
      achieve stability result in formulations that are not osmotically compatible with
      the subcutaneous (SC) or intramuscular (IM) injection of a typical dose of
      plasmid DNA. In an effort to reduce the formulation osmolality, dextrans
      possessing a range of molecular weights were investigated for their ability to
      serve as protectants. Dextran 3000 proved to be the most effective of the
      dextrans tested, and offered similar protection to sucrose on a weight basis.
      However, the advantage of employing this excipient is that the resulting
      osmolality is reduced by approximately 40% as compared to an equivalent weight of
      sucrose. Moreover, the use of dextran allows lyophilized vector preparations to
      be rehydrated to reduced volumes, essentially concentrating vectors prior to
      administration. Utilizing a combination of dextran 3000 and sucrose, we
      demonstrate that complexes of polyethylenimine (PEI) and DNA lyophilized at 0.1
      mg/mL can be concentrated tenfold upon rehydration, resulting in an isotonic
      formulation containing 1 mg/mL DNA that can provide more realistic injection
      volumes for animal studies, and is compatible with clinical trials involving SC
      and IM injection.

PMID- 15858858
TI  - Lipid binding region (2303-2332) is involved in aggregation of recombinant human
      FVIII (rFVIII).
AB  - Factor VIII (FVIII) is a multi-domain protein that is important in the clotting
      cascade. Its deficiency causes Hemophilia A, a bleeding disorder. The unfolding
      of protein domains can lead to physical instability such as aggregation, and
      hinder their use in replacement therapy. It has been shown that the aggregation
      of rFVIIII is initiated by small fluctuations in the protein's tertiary structure
      (Grillo et al., 2001, Biochemistry 40:586-595). We have investigated the
      domain(s) involved in the initiation of aggregation using circular dichroism
      (CD), size exclusion chromatography (SEC), fluorescence anisotropy, domain
      specific antibody binding, and clotting activity studies. The studies indicated
      that aggregation may be initiated as a result of conformational change in the C2
      domain encompassing the lipid-binding region (2303-2332). The presence of O
      phospho-L-Serine (OPLS), which binds to the lipid-binding region of FVIII,
      prevented aggregation of the protein.

PMID- 15858860
TI  - Bibliography. Current world literature. Seizure disorder.

PMID- 15858859
TI  - Evaluation of buccal methyl-beta-cyclodextrin toxicity on human oral epithelial
      cell culture model.
AB  - Cyclodextrins, especially methylated beta-cyclodextrins offer several advantages
      for drug delivery which include improved drug solubilization, protection against
      physicochemical and enzymatic degradation, as well as a potential for absorption
      improvement. However, little or no data are available for their use as drug
      penetration enhancer via the buccal route. This study focuses on the toxicity of
      randomly methylated beta-cyclodextrin (RAMEB) on buccal mucosa using a
      reconstituted human oral epithelium model composed of TR 146 cells. Toxicity of
      RAMEB on TR 146 cells was evaluated by measuring cell viability (MTT assay) and
      membrane damages followed by LDH release after single and repeated exposures to
      RAMEB solutions. Inflammatory effects of RAMEB are also considered by measuring
      expression of interleukin-1alpha and are supported by histological examination.
      The present results indicate that 10% RAMEB results in cytotoxic and inflammatory
      effects depending on time exposure, whereas 2% and 5% RAMEB do not induce tissue
      damages even after 5 days of repeated exposures. Therefore, the highly water
      soluble RAMEB is thought to be a safe candidate as an excipient for buccal
      mucosal drug delivery.

PMID- 15858861
TI  - Nuclear imaging of an extraskeletal retroperitoneal osteosarcoma: respective
      contribution of 18FDG-PET and (99m)Tc oxidronate (2005:1b).
AB  - Extraskeletal osteosarcoma (ExOs) is a rare, usually highly aggressive
      malignancy, which affects individuals beyond the fifth decade of life. ExOs
      prinicipally occurs as a soft tissue mass in a limb or retroperitoneum. We
      present the case of a 58-year-old man with a huge abdominal mass who underwent a
      complete range of clinical imaging investigations including computed tomography
      (CT), skeletal scintigraphy (BS) and positron emission tomography (PET). These
      exams showed a central calcified and ossified, strongly metabolic retroperitoneal
      tumour suggestive of an ExOs. This diagnosis was later confirmed by
      histopathology. To our knowledge, such a case has not previously been documented
      fully using radiological imaging correlated to modern nuclear medicine techniques
      such as PET.

PMID- 15858863
TI  - Contact allergy in the burning mouth syndrome: a retrospective study on 38
      patients.

PMID- 15858864
TI  - Warthin's tumour, a rare false positive on positron emission tomography in
      melanoma staging.

PMID- 15858865
TI  - Lower phenytoin serum levels in persons switched from brand to generic phenytoin.

PMID- 15858866
TI  - Clinically mild encephalitis/encephalopathy with a reversible splenial lesion.

PMID- 15858867
TI  - Management of hepatocellular carcinoma in the waiting list before liver
      transplantation.

PMID- 15858868
TI  - Healthy eating. Asian cuisine. Introducing East to West.

PMID- 15858869
TI  - Exercise paradox. Know your risk profile.

PMID- 15858870
TI  - Healthy kidneys. No joking matter.

PMID- 15858871
TI  - Fast food & restaurant fare. Sonic. America's Drive-In.

PMID- 15858872
TI  - Lone star. San Antonio told Jeff Kapche that the couldn't be a cop because he
      used insulin. Jeff and and his lawyer, John Griffin, teamed up to fight the
      decision.

PMID- 15858873
TI  - Get a "grip!" Diabetes and your hands. Diabetes can affect the muscles and joints
      of your hands. Here's how to stay dexterous.

PMID- 15858874
TI  - Shedding pounds for life. Slashing the fat. Many types of diets can result in
      weight loss, but only one has been shown to keep weight off long term.

PMID- 15858875
TI  - Shedding pounds for life. Burning extra calories. Exercise is essential for
      avoiding unwanted pounds.

PMID- 15858876
TI  - Shedding pounds for life. Breakfast: the forgotten meal. To maintain a healthy
      weight, get a bright and early start on good nutrition.

PMID- 15858877
TI  - Shedding pounds for life. Dear diary... Keeping a food diary can help keep you
      honest about your eating habits.

PMID- 15858878
TI  - Shedding pounds for life. Tipping the scales. Catch and correct weight problems
      early through weekly weigh-ins.

PMID- 15858879
TI  - Shedding pounds for life. Been there done that. Successful weight losers share
      their secrets for keeping weight off for good.

PMID- 15858880
TI  - Shedding pounds for life. Tackling teenage type 2. Helping teens control their
      weight is key to preventing type 2 diabetes in young people.

PMID- 15858881
TI  - Shedding pounds for life. How a dietitian can help. In the war against weight
      gain, a registered dietitian can be your most important ally.

PMID- 15858882
TI  - Research profile. They glycemic index. A measure of type 2 risk? Angela D. Liese,
      PhD, MPH.

PMID- 15858883
TI  - Jump into summer. New exercise routines to get you going.

PMID- 15858884
TI  - Just the facts. The importance of diabetes research.

PMID- 15858885
TI  - Senior care. Assisted living facilities.

PMID- 15858886
TI  - C-reactive protein: a red light for your health. C-reactive protein is necessary
      for defending your body from injury and infection. But too much of it means
      trouble is brewing.

PMID- 15858887
TI  - Longest survivor? Taking good care of his diabetes has helped Karl Smith stay in
      good health for the 81 years he's been on insulin.

PMID- 15858888
TI  - Living with low vision. A personal point of view.

PMID- 15858889
TI  - Real life cooking. Cooking for kids & teens. Sneak in some extra nutrition with
      these smart strategies and yummy recipes.

PMID- 15858891
TI  - Real life cooking. Great meals, few ingredients. Fresh ingredients and a little
      know-how can help you do more with less.

PMID- 15858890
TI  - Real life cooking. Fixing the family favorites. A few adjustments and
      substitutions will let you have your favorite recipes and eat them, too!

PMID- 15858892
TI  - Real life cooking. Meals on the go. Living in the fast lane doesn't have to mean
      throwing nutrition out the window.

PMID- 15858893
TI  - Real life cooking. Sweet selections. Sure, you can eat sugar. But with so many
      other sweetener options, you might not want to.

PMID- 15858894
TI  - Neuropathy. Diabetes isn't always to blame.

PMID- 15858895
TI  - Research profile. Warding off type 2. Can taking glitazones cut the risk? Philip
      A. Kern, MD.

PMID- 15858896
TI  - A healing heart. Don't forget diabetes.

PMID- 15858897
TI  - Carbohydrates. Revisiting an old friend.

PMID- 15858898
TI  - Back to basics. Types of diabetes.

PMID- 15858899
TI  - An "ouchless" future? Will the day come when you no longer have to prick, stick,
      jab or stab to check your glucose levels?

PMID- 15858900
TI  - Overcoming the psychological challenge to weight loss.

PMID- 15858901
TI  - Lows and your pregnancy. Tight control of your blood glucose during pregnancy is
      good for both you and your baby, but it may put you at risk for low blood
      glucose. Here are tips on avoiding lows, and what to do if you have one.

PMID- 15858902
TI  - Everybody loves crepes. It's not only easy, but fun, to prepare this world-class
      dish.

PMID- 15858903
TI  - Research profile. Treating prediabetes. Exercise, metformin, or both? Barry
      Braun, PhD.

PMID- 15858904
TI  - [Quality of life before and after thyroplasty for vocal fold paralysis].
AB  - OBJECTIVES: The aim of our prospective study was to evaluate the vocal handicap
      in relation with the quality of life in patients with unilateral vocal fold
      paralysis (UVFP), before and after thyroplasty with Montgomery implant (type I).
      METHODS: Ten patients had to file the VHI questioner before and three months
      after thyroplasty. The 30 items of the Voice Handicap Index scale are sub-divided
      in 3 categories referring to "Functional", "Physical" and "Emotional" dimensions.
      RESULTS: Before thyroplasty, the global score and the 3 sub-scales rating are
      high reflecting severe impairment in speech communication (VHI total = 65,9/120,
      F = 25.7/40, E = 19.9/40, P = 20.8/40). Three months after thyroplasty, a
      significant improvement is found predominantly in the field of functional and
      emotional evaluation, corresponding to an improved quality of social life (VHI
      total = 20,9/120, F = 6.3/40, E = 3.6/40, P = 10.6/40). CONCLUSION: These results
      show the interest in using the autoevaluation VHI scale as a complementary
      evaluation associated to perceptual, acoustic and aerodynamic evaluation to
      objectify the functional improvement in voice quality after thyroplasty.

PMID- 15858905
TI  - Nuclear alterations of cells and atypical metaplastic cells in cervical smears
      are predictive criteria of high-grade cervical intraepithelial neoplasia.
AB  - Diagnoses based on the screening of cervical smears show low interobserver
      reproducibility and are frequently discordant with the final histological
      diagnosis. The aim of this study was to identify which of the cytomorphologic
      criteria used in the screening of cervical smears were most predictive of the
      histopathological grades of cervical intraepithelial neoplasia. The abnormal
      cervical smears of 206 women were reviewed blindly according to 22 pre
      established cytomorphological criteria. Colposcopic evaluation was carried out in
      all cases. The marked presence of several nuclear criteria frequently found
      together in the same smear was associated with high grade intraepithelial
      neoplasia regardless of the presence of any other criteria. On the other hand,
      when the nuclear criteria were less evident, the cluster of criteria related to
      metaplastic cells was predictive of a diagnosis of high-grade intraepithelial
      neoplasia. Focusing on selected cytological criteria can aggregate predictive
      value to cervical smear diagnoses.

PMID- 15858907
TI  - Free the academic drug tests.

PMID- 15858906
TI  - Red Cross find detainee abuse in Guantanamo; US rejects accusations; confidential
      report calls practice tantamount to torture.

PMID- 15858909
TI  - Pharmacies balk on after-sex pill and widen fight; right of refusal cited; many
      states take up the issue; citing religious and moral concerns.

PMID- 15858910
TI  - France lets terminally ill refuse care, but still bans euthanasia.

PMID- 15858911
TI  - Dental devices; reclassification of tricalcium phosphate granules and
      classification of other bone grafting material for dental bone repair. Final
      rule.
AB  - The Food and Drug Administration (FDA) is reclassifying tricalcium phosphate
      (TCP) granules for dental bone repair from class III to class II (special
      controls), classifying into class II (special controls) other bone grafting
      material for dental indications, and revising the classification name and
      identification of the device type. Bone grafting materials that contain a drug
      that is a therapeutic biologic will remain in class III and continue to require a
      premarket approval application. The classification identification includes
      materials such as hydroxyapatite, tricalcium phosphate, polylactic and
      polyglycolic acids, or collagen. This action is being taken to establish
      sufficient regulatory controls that will provide reasonable assurance of the
      safety and effectiveness of these devices. Elsewhere in this issue of the Federal
      Register, FDA is announcing the availability of the guidance document that will
      serve as the special control for the class II devices.

PMID- 15858912
TI  - [Observations on physician's contributions to professional publishing].

PMID- 15858913
TI  - [Contribution to a discussion on general medicine and medical schools].

PMID- 15858914
TI  - [The required medico-social approach of epilepsy].

PMID- 15858915
TI  - [Behcet's disease].
AB  - Behcet's disease is a vasculitis of unknown origine. Mucocutaneous manifestations
      are necessary for diagnosis. Ocular and neurological involvements can lead to
      severe impairment. Arterial involvement may be lethal. Treatment is only
      symptomatic using steroids, colchicine and antiaggregant therapy.
      Immunosuppressive drugs are generally given for severe manifestations resistant
      to conventional therapy. Alpha interferon and infliximab are interesting in case
      of failure or relapses despite treatment. As in all chronic diseases, education
      and good observance are needed to improve prognosis.

PMID- 15858916
TI  - [Epilepsy. Important progress in diagnosis and therapy].

PMID- 15858917
TI  - [Syndromic approach of epilepsy: usefulness for therapeutic choices].
AB  - The international classification of the epilepsies and epileptic syndromes is a
      useful tool to classify epilepsies with major therapeutic and prognostic
      implications. The current classification is based on clinical,
      electroencephalographic and aetiological criteria that allow the definition of
      distinct syndromes with a common clinical presentation, and prognosis. Epileptic
      syndrome are separated according to their topography (focal, generalized,
      undetermined) and to their presumed aetiology (idiopathic, cryptogenic,
      symptomatic). Its widespread utilisation has greatly contributed to the current
      understanding of epilepsy. It is now well known that inappropriate anti-epileptic
      drugs may cause worsening of seizures and that the syndromic epilepsy type may
      guide to select the adequate treatment. The syndromic classification brings also
      major prognostic informations that may be useful to the practitioners and their
      patients.

PMID- 15858918
TI  - [Exams in epilepsy: how? for whom? how far?].
AB  - The diagnosis of epilepsy remains clinical. However some investigations must be
      carried out in order to confirm the diagnosis, establish the epileptic syndrome
      with accuracy and seek the etiology. The first line investigations are EEG,
      morphological imaging (cerebral MRI, CT scan) as well as standard blood test. The
      latter also permit patient management in some cases. Indeed, video-EEGs
      monitoring are used to explore refractory epilepsy in order to optimize treatment
      or carry out presurgical assessment. In this paper, we present these
      investigations after which we discuss how they are to be used.

PMID- 15858919
TI  - [Management of a first epileptic seizure in adults].
AB  - Management of a first seizure is a frequent challenge in the emergency room.
      Definite diagnosis is mandatory before treatment, identification of the epileptic
      syndrome is recommended. The overall recurrence rate of a first unprovoked
      seizure is about 50%, but varies considerably depending on several risk factors
      (neurological deficit in particular, a congenital one, Todd's paralysis,
      significant psychiatric disorders, epilepsy in siblings, symptomatic seizures
      (MRI is the standard procedure now to detect a structural lesion, except in case
      of a idiopathic generalised epilepsy and epilepsy with centro-temporal spikes)
      and epileptiform abnormalities on EEG which should be obtained within 24 hours
      after a seizure. Each treatment decision has to be taken individually after
      discussion with the patient. Early treatment reduces the 2 years recurrence rate
      but doesn't alter the long term prognosis.

PMID- 15858920
TI  - [Therapeutic strategy in epileptic patients].
AB  - Choosing an antiepileptic drug is crucial because it will be usually taken for
      many years by the patient. The development of several new drugs makes drug
      selection more complicated and challenging, but may be a better adaptation to the
      individual patient's characteristics is now easier. The main criterion of choice
      is the use of the international classification of the epileptic syndrome
      (generalised or partial) because some antiepileptic drugs may have a deleterious
      effect on some epileptic syndromes. Compared efficacy is not a good criterion as
      when the international classification is correctly used, the efficacy of the old
      and new medications seems to be not significantly different. The newer drugs may
      be better tolerated, have fewer drug interactions, and seem to affect cognitive
      functions to a lesser extent than old drugs, but data on the new drugs are more
      limited than for older ones. The choice is then guided by the individual
      appreciation of the risk-benefit ratio in each patient. There are special
      situations and populations where special recommendations can be done, and a new
      antiepileptic drug seems to be the better first line drug (West syndrome with
      tuberous sclerosis, women of childbearing potential; elderly population). The
      arrival of the new antiepileptic drugs makes possible a better adaptation of the
      treatment to the individual patient.

PMID- 15858921
TI  - [Management of status epilepticus].

PMID- 15858922
TI  - [Surgery of the epilepsy, orientation of patients, stages and results].
AB  - The increasing number of the presurgical epilepsy unit, and the standardisation
      and simplification of presurgical methods have allowed the development of
      surgical treatment of pharmacoresistant epilepsy. Pharmacoresistance can be
      diagnosed and surgical treatment proposed after two years of medicinal treatment.
      High resolution MRI is a deciding technique for epileptic focus localization. A
      focal lesion or unilateral Ammon's horn sclerosis are very favourable predictiv
      factor for surgery's success. Patient presenting temporal lobe epilepsy combined
      with this anomalie can be offered temporal lobectomy straight away with 80%
      chance of success. In other cases, intracranial electrodes can help to localise
      the epileptic cortex and enable surgery. Surgical treatment of pharmacoresistant
      epilepsy should not be reserved to severe forms but considered as soon as
      surgical favourable predictive factor has been established.

PMID- 15858924
TI  - [Epilepsy: true or false].

PMID- 15858923
TI  - [Epilepsy and road legislation].
AB  - As regards road safety, the doctors have the duty to inform their patients on the
      affections incompatible, transitorily or in a final way, with control of a
      vehicle. In the majority of the countries, the very large majority of the
      epileptics is not in rule with respect to this legislation with regard to the
      private cars. Moreover, the legislation is too restrictive for the drivers of
      group 2. After having begun again the conditions for application of the French
      and European current legislation, the authors specifie the later upgrading
      capabilities relating to the epilepsy.

PMID- 15858925
TI  - [Evaluation of medical practice and simulated patients].

PMID- 15858926
TI  - [Breast tumours].

PMID- 15858927
TI  - [Hepatomegaly and abdominal masses. Diagnostic approach].

PMID- 15858928
TI  - [Exanthem--erythrodermia. Diagnostic approach].

PMID- 15858929
TI  - [Paget's disease of bone].

PMID- 15858930
TI  - [Digestive parasitosis: giardiasis, taeniasis, ascariasis, enterobiasis,
      amoebiasis, hydatidosis].

PMID- 15858931
TI  - [The creation of the first children's hospital: the dream and the reality].

PMID- 15858932
TI  - Interventional treatment for very young adults with acute myocardial infarction.
      Clinical manifestations and outcome.
AB  - Direct percutaneous coronary intervention (PCI) for acute myocardial infarction
      (AMI) is now established as a standard therapy for older patients. However,
      experience with PCI in very young adults with AMI has been limited. In this
      report we retrospectively evaluated the effectiveness of PCI for very young
      adults with AMI and estimated their clinical characteristics and outcome. Of the
      502 patients with AMI, 5 were 35 years old or younger (1.0%) during a period of 4
      years (2000--2004). We assessed the utility of PCI in these five consecutive
      patients under the age of 35 presenting with a first AMI. Five AMI patients,
      ranging in age from 20 to 34 years (median, 27+/-5 years) underwent direct PCI
      for the culprit lesions. The lesions targeted for PCI were located in the left
      anterior descending artery in 3 patients and in the right coronary artery in 2
      patients. One patient had a past history of Kawasaki disease (KD). In all of the
      patients, PCI were angiographically effective at the acute phase without
      complication. In hospital course, a subacute stent thrombosis occurred in one
      patient. Follow-up angiograms performed 6 months after the procedure revealed no
      restenosis, but identified a new coronary aneurysm in one patient with a past
      history of KD and a regressed giant coronary aneurysm probably due to atypical KD
      in another patient, which were confirmed by intravascular ultrasound. There was
      one death ascribed to heart failure 8 months after the initial PCI. The findings
      of this report suggest that PCI for very young adults with AMI can be safe and
      effective in the short-term.

PMID- 15858933
TI  - Comparative inhibitory effects of cilostazol and ticlopidine on subacute stent
      thrombosis and platelet function in acute myocardial infarction patients with
      percutaneous coronary intervention.
AB  - We compared the effects of ticlopidine and cilostazol on the prevention of
      subacute stent thrombosis (SAT) in acute myocardial infarction (AMI) patients
      with stenting. We also analyzed the cause of the difference by measuring platelet
      aggregation activity. Consecutive patients who underwent successful stenting for
      AMI between March 2001 and March 2004 were analyzed. In addition to aspirin (100
      mg/day), cilostazol (200 mg/day) was administered to 99 cases between March 2001
      and May 2002 and ticlopidine (200 mg/day) was administered to 85 cases between
      June 2002 and February 2004. The incidence of SAT within four weeks after
      stenting was analyzed. Thirty-eight AMI patients were randomized and their
      platelet aggregation activity was measured using a laser-scattered aggregometer
      (18 cases in the cilostazol group and 20 cases in the ticlopidine group). SAT did
      not occur in the ticlopidine group while 5 cases (5.1%) of SAT occurred in the
      cilostazol group (P < 0.05). The inhibitory activity of cilostazol for ADP
      induced platelet aggregation was lower than that of ticlopidine (P < 0.05).
      Cilostazol with aspirin after stenting in AMI patients showed more frequent SAT
      than ticlopidine with aspirin. One of the causes for this difference was
      speculated to be the weaker inhibitory activity of cilostazol for ADP-induced
      platelet aggregation.

PMID- 15858934
TI  - The incidence of stent-edge spasm after stent implantation in patients with or
      without vasospastic angina pectoris.
AB  - Although several investigations have reported that stent implantation is an
      option for the treatment of vasospastic angina (VSA) that is resistant to medical
      treatment, we are concerned about the occurrence of new stent-edge spasms after
      stenting. The purpose of this study was to determine the incidence of new stent
      edge spasms after stenting. Twenty-seven patients with VSA and 23 patients
      without VSA were enrolled. About 6 months after stent implantaion, a spasm
      provocation test was performed by intracoronary infusion of acetylcholine or
      ergonovine in 26 patients with VSA and all patients without VSA, and the induced
      stent-edge spasms were classified as either moderate (stent-edge spasm > 75% and
      < 95% reduction in coronary artery diameter) or severe (stent-edge spasm > 95%
      reduction in coronary artery diameter). In one patient with VSA, stent-edge spasm
      and acute thrombosis occurred several hours after stent implantation. The
      remaining 26 patients with VSA had no complications during or after stent
      implantation. However, during the chronic phase, severe stent-edge spasm was
      provoked in 5 patients with VSA (19.2%) and in 2 patients without VSA (8.7%).
      Moderate stent-edge spasm was provoked in 5 patients with VSA (19.2%) and 5
      patients without VSA (21.7%). The results suggest new onset stent-edge spasm in
      patients either with or without VSA should not be neglected.

PMID- 15858935
TI  - Utilization of a double-wire technique to treat long extended spiral dissection
      of the right coronary artery. Evaluation of incidence and mechanisms.
AB  - While coronary artery dissection caused by a guiding catheter, which is one of
      the most commonly occurring complications during diagnostic cardiac
      catheterization or coronary intervention, has various forms, extensive antegrade
      and retrograde dissections of the right coronary artery (RCA) are rarely observed
      during these procedures. Within the last three years, we retrospectively reviewed
      our experience with 12,600 consecutive patients who underwent either diagnostic
      cardiac catheterization or coronary angioplasty, and found that 17 (0.14%) of the
      patients displayed extensive antegrade and retrograde RCA dissection. The
      antegrade dissection always propagated to the distal RCA either on bifurcation of
      the posterior descending artery and posterolateral artery (PLA) or to the
      proximal PLA. The retrograde dissection was always observed close to the ostium
      of the RCA or extending to the ostium of the RCA. TIMI-0 flow in the RCA was
      immediately observed in all the patients. Chest pain associated with an
      electrocardiogram showing ST-segment elevation was soon observed in most of the
      patients. The true lumen could be entered successfully using a single wire in 8
      of 17 patients. However, a double-wire technique was required for 7 patients.
      This technique involved first advancing a wire along to the false lumen and then
      pulling back the guiding catheter away from the ostium of the RCA for a few
      millimeters followed by anchoring with the wire. Another wire was then gently
      inserted into the true lumen from the dissection entrance point, which was
      located near or at the ostium of RCA, and carefully advanced to the distal RCA.
      Coronary stenting was successfully deployed in 15 patients. However, the
      procedure failed in 2 patients. Furthermore, this complication caused 7 patients
      to have acute myocardial infarctions, 2 patients to develop atrial fibrillation,
      and I to die from ischemic enterocolitis due to cardiac embolism after 7 months
      of follow-up. In conclusion, with an increase in experience, we now better
      understand this complication. However, this complication, which is a formidable
      challenge for coronary intervention, may be a life-threatening complication, and
      patients with this complication may face the potential risk of a nonfatal
      myocardial infarction, or even a long-term fatal outcome in the long-term.
      Accordingly, it is important to learn how to promptly manage this complication.

PMID- 15858936
TI  - Beneficial effect of the addition of nitroglycerin to the cardioplegic solution
      on lipid peroxidation during coronary artery bypass surgery.
AB  - The effects of the addition of a nitric oxide (NO) donor to the cardioplegic
      solution on reperfusion injury and lipid peroxidation (LPO) in coronary artery
      bypass grafting (CABG) are not known. Therefore, this work was conducted to
      determine the possible effects of nitroglycerin on LPO and reperfusion injury as
      a result of CABG. A prospective double-blind, placebo-controlled study was
      conducted in 30 consecutive patients with coronary artery disease who underwent
      CABG with cardiopulmonary bypass. The patients were randomly assigned to receive
      3 microg/kg of nitroglycerin added to the cardioplegic solution (NTG group) or 3
      microg/kg of placebo added to the cardioplegic solution (placebo group). MDA
      increased significantly in the placebo group compared to the NTG group during the
      ischemic (P < 0.01) and reperfusion periods (P < 0.01). The level of troponin I
      decreased significantly in the NTG group compared to the placebo group during the
      ischemic and reperfusion periods (P < 0.001). The level of NO increased
      significantly in the NTG group compared to the placebo group during the ischemic
      and reperfusion periods (P < 0.01). LPO was increased in response to CPB during
      CABG, together with simultaneous decreases in serum nitric oxide levels, whereas
      LPO was significantly decreased in response to CPB with nitroglycerin, together
      with simultaneous increases in the levels of serum nitric oxide.

PMID- 15858937
TI  - Establishing a prediction model for coronary angiography based on coronary risk
      factors.
AB  - The aim of the present study was to establish an evidence-based effective
      prediction model for improving the accuracy and priority for undertaking coronary
      angiography. The sample population consisted of 2002 coronary angiography
      patients. Our data were taken from claim forms provided by the Taiwanese Bureau
      of National Health Insurance. The results were tested using chi-square automatic
      interaction detection to establish a prediction model using coronary risk
      factors. We found significant variation across homogeneous groups, with the
      probabilities of developing coronary heart disease (CHD) varying according to
      risk factors such as sex, hypertension, diabetes, age, and physical inactivity.
      The study also explored the influence of interactions among patient
      characteristics. The sensitivity, specificity, and positive predictive value of
      our study were 92.0%, 35.4%, and 76.5% respectively, indicating the diagnostic
      accuracy of the model is at least as high as the treadmill exercise test. The
      results suggest that the accuracy of a decision concerning the performance of
      cardiac angiography can be significantly enhanced by an evidence-based effective
      prediction model that takes interactions between risk factors into account. This
      model also helps to priortize patients waiting to undergo coronary angiography.

PMID- 15858938
TI  - Intraortic pulse pressure is correlated with coronary artery stenosis.
AB  - There is increasing evidence that peripheral pulse pressure measured at the
      brachial artery is a good predictor of coronary heart disease. However, the
      relation between pulse pressure and angiographically demonstrated coronary artery
      stenosis has not been fully elucidated. We designed the present study to
      investigate the association of the various components of blood pressure, such as
      systolic pressure, diastolic pressure, and pulse pressure of both peripheral and
      central arteries with angiographically determined coronary artery stenosis.
      Levels of aortic systolic pressure, aortic diastolic pressure, aortic pulse
      pressure, peripheral systolic pressure, peripheral diastolic pressure, and
      peripheral pulse pressure were determined in 323 patients who underwent
      diagnostic coronary angiography. Of these 323 patients, 215 patients had
      significant organic coronary artery stenosis. Aortic pulse pressure was
      significantly higher in patients with coronary artery stenosis (P = 0.0050).
      Aortic diastolic pressure was lower in patients with coronary artery stenosis
      (marginally significant, P = 0.0462). However, no statistically significant
      difference was observed between other blood pressure components and coronary
      artery stenosis. Multivariate analyses showed that aortic pulse pressure was
      associated with coronary artery stenosis independently of aortic diastolic
      pressure. Moreover, aortic pulse pressure was positively correlated with the
      number of vessels involved (P = 0.0024). The results of the present study
      indicate that aortic pulse pressure is significantly and independently correlated
      with angiographically determined coronary artery stenosis.

PMID- 15858939
TI  - High diastolic blood pressure during exercise is associated with
      hypercholesterolemia in patients with coronary artery disease.
AB  - Evaluating blood pressure response during exercise rather than during rest might
      better detect a subtle impairment in relaxation of the resistance vessel in
      hypercholesterolemia. We examined the relation between serum cholesterol and
      blood pressure response during exercise in patients with coronary artery disease.
      One hundred and forty-eight consecutive patients with coronary artery disease
      were monitored during symptom-limited incremental exercise testing with a cycle
      ergometer. Cuff blood pressure was measured every minute during exercise testing
      with an automatic indirect manometer. Although there were no significant
      differences in systolic or diastolic blood pressure at rest between the patients
      with hypercholesterolemia (total cholesterol > or = 220 mg/dL, n = 39) and those
      without it (n = 109), the former reached a higher diastolic blood pressure at
      peak exercise (94.8+/-16.0 versus 87.8+/-12.9 mmHg, P = 0.007). The increase in
      diastolic blood pressure at peak exercise versus the resting value in the
      patients with hypercholesterolemia was 20.6+/-11.3 mmHg, and this was
      significantly higher than the increase in patients without hypercholesterolemia
      (14.8+/-11.8 mmHg, P = 0.009). However, there were no differences in the peak
      exercise systolic blood pressure and the magnitude of the increase in systolic
      blood pressure between the two groups. Among the patients with coronary artery
      disease in our study, we found that those with hypercholesterolemia had
      significantly higher diastolic blood pressure during exercise than those without
      hypercholesterolemia, strongly suggesting that patients with hyperlipidemia are
      at a higher risk of developing hypertensive complications.

PMID- 15858940
TI  - The role of angiotensin converting enzyme genotype in coronary artery ectasia.
AB  - Coronary artery ectasia (CAE) is characterised by irregular, diffuse, saccular,
      or fusiform dilatation of the coronary arteries. Although the underlying
      mechanisms are not fully understood, CAE is considered to be an original form of
      vascular remodelling in response to atherosclerosis. However, it is not clear why
      some patients develop CAE while most do not. Experimental data suggest that
      activation of the renin angiotensin system may lead to an increased inflammatory
      response in the vessel wall or to an activation of matrix metalloproteinases. In
      addition, an insertion/deletion (ID) polymorphism of angiotensin converting
      enzyme (ACE) has been associated with coronary vascular tone and the development
      of aneurysms. Accordingly, we hypothesised that the gene polymorphism of ACE may
      be a potential factor influencing the genesis of CAE. We retrospectively
      evaluated 112 patients who underwent coronary angiography. ACE ID genotype was
      determined in two groups of patients. Group 1 consisted of 56 patients who were
      found to have CAE. Group 2 consisted of 56 patients with significant coronary
      artery disease (CAD) (> 50% stenosis in any of the major epicardial coronary
      arteries or their branches) but without any evidence of coronary ectasia.
      Polymerase Chain Reaction (PCR) was used to detect ACE genotype. The ratio of DD
      genotype was found to be greater in group 1 than group in 2 (39% versus 18%,
      respectively, P < 0.05). When assessed according to the presence of the I allele,
      it was greater was greater in group 2 than in group 1 (82.1% versus 60.7%,
      respectively, P < 0.05). The results indicate that an ACE DD genotype may be a
      risk factor for CAE.

PMID- 15858941
TI  - Primary congenital anomalies of the coronary arteries: a coronary arteriographic
      study in Western Turkey.
AB  - Coronary artery anomalies are found in 0.6% to 1.5% of coronary angiograms.
      Angiographic recognition of these vessels is important because of their clinical
      significance and importance in patients undergoing coronary angioplasty or
      cardiac surgery. We reviewed the database of the Cardiac Catheterization
      Laboratory of Uludag Medical University in Bursa, Turkey. All patients who were
      subjected to coronary angiography from 1994 to 2001 were included. The study
      included 12,059 patients who underwent diagnostic coronary arteriography during
      the 8 year period. One hundred patients had primary congenital coronary
      anomalies. Ninty-five (95%) of the patients had anomalies of origin and
      distribution while five (5%) had coronary artery fistulae. The left main coronary
      artery (LMCA) was the most common anomalous vessel involved (forty-eight (48%) of
      the patients). An LMCA distribution anomaly was observed in these 48 patients. An
      anomalous right coronary artery (RCA) was the second most common anomaly, seen in
      twenty-two (22%) of the patients. An anomalous circumflex artery (Cx) was the
      third most common anomaly, seen in seventeen. Five patients had a coronary artery
      fistulae. The fistulae in our series were small without significant shunt
      circulation. Primary congenital coronary anomalies are isolated lesions and
      generally have no relation with other congenital heart diseases. They do not
      appear to be associated with an increased risk for development of coronary
      atherosclerosis. Angiographic recognition of these vessels is important because
      of their clinical significance and importance in patients undergoing coronary
      angioplasty or cardiac surgery.

PMID- 15858942
TI  - Surgical treatment of left-sided prosthetic valve thrombosis: short and long-term
      results.
AB  - We report a single center experience of surgical treatment of 30 cases of left
      sided prosthetic valve thrombosis (PVT). In our series, a diagnosis of PVT was
      established based on clinical and echocardiographic examinations. Thrombosis was
      the major etiologic factor in 25 patients (83.3%), while 22 of 25 patients (88%)
      had a subtherapeutic anticoagulation level. The early hospital mortality rate was
      7.1% in patients with New York Heart Association (NYHA) functional classes II -
      III, and 31.3% in NYHA functional class IV. The median interval from the surgical
      procedure to follow-up for these patients was 29.2 months. No recurrence or
      deaths were observed during 3 to 73 months following the surgical procedure.

PMID- 15858943
TI  - Immunosuppressive treatment for inflammatory cardiomyopathy: meta-analysis of
      randomized controlled trials.
AB  - The use of immunosuppressive therapy for inflammatory cardiomyopathy is
      controversial. The aim of this review is to summarize the current empirical
      evidence for immunosuppressive treatment in inflammatory cardiomyopathy. We
      conducted a meta-analysis of all randomized controlled trials (RCTs) that
      compared immunosuppressive therapy with either placebo or conventional treatment
      in patients with inflammatory cardiomyopathy. The pooled outcomes were all-cause
      death and heart transplantation for inflammatory cardiomyopathy, left ventricular
      ejection fraction (LVEF), and left ventricular end diastolic dimension (LVEDD).
      Five trials involving 316 patients were included. Overall, immunosuppressive
      therapy was not superior to placebo and conventional therapy in the pooled
      outcome of all-cause death and heart transplantation (odds ratio [OR] 1.03, 95%
      confidence intervals [CI] 0.58 to 1.80) in the long-term. The pooled data showed
      that there might be a short-term beneficial effect on LVEF improvement (5.06%,
      95% CI -0.07% to 10.18%) in patients receiving immunosuppressive therapy, but no
      beneficial effect on LVEDD either in the short-term (-0.87 mm; 95% CI, -8.29 to
      6.55 in adult patients) or long-term (-0.52 mm, 95% CI -3.64 to 2.60 in adult
      patients) was observed. There is no evidence to suggest that immunosuppressive
      therapy has an effect on improving the survival of patients with inflammatory
      cardiomyopathy. Current therapy in inflammatory cardiomyopathy seems to be
      limited to supportive measures or transplantation.

PMID- 15858944
TI  - Value of left atrial function in predicting exercise capacity in heart failure
      with moderate to severe left ventricular systolic dysfunction.
AB  - Left atrial (LA) function is associated with left ventricular (LV) diastolic
      filling and cardiac output response to exercise. But the relation between LA
      function and exercise performance has not been adequately evaluated. The aim of
      this study was to investigate the relation between LA function and exercise
      capacity in dilated cardiomyopathy (DCM) with cardiopulmonary exercise testing.
      Forty-four patients with a left ventricular end-diastolic dimension (LVDd) > or =
      60 mm and an ejection fraction (EF) < or = 40%, and in normal sinus rhythm were
      included in this study. Patients were divided into group 1 and group 2 according
      to their exercise peak oxygen uptake (VO2) (group 1: peak VO2 >14 mL/kg/min,
      group 2: peak VO2 < or = 14 mL/ kg/min). LA function indices were defined as
      follows: LA end-systolic diameter (LASd), end-diastolic diameter (LADd), LA
      systolic volume (LASV), LA diastolic volume (LADV), LA ejection volume (LAEV),
      and LA ejection fraction (LAEF). LASd, LADd, LASV, and LADV were significantly
      increased in group 2 (P < 0.001, P < 0.001, P < 0.05, P < 0.005). Group 1 had
      significantly higher LAEF (P < 0.001 ) and LVEF (P < 0.05). Group 2 had
      significantly shorter exercise duration, and decreased anaerobic threshold levels
      and minute ventilation volumes (P < 0.001, P < 0.001, P < 0.005 ). There was a
      positive correlation between peak VO2 and LVEF (r = 0.46, P = 0.002), and LAEF (r
      = 0.61, P < 0.001), peak A wave velocity (r = 0.39, P = 0.009), E wave
      deceleration time (r = 0.56, P < 0.001), and isovolumic relaxation time (IVRT) (r
      = 0.35, P = 0.04). There was a negative correlation between peak VO2 and LASd (r
      = -0.53, P < 0.001) LADd (r = -0.59, P < 0.001), LASVI (r = -0.34, P = 0.027),
      LADVI (r = -0.37, P = 0.001), and the E/A ratio (r = -0.41, P = 0.006), Decreased
      LAEF and increased LA sizes were associated with decreased peak VO2. The results
      clearly demonstrate that LA functions at rest are related to exercise performance
      in patients with heart failure.

PMID- 15858945
TI  - Experimental study of a multiplaned mechanical aortic valve using bovine aorta.
AB  - A newly designed multiplaned mechanical aortic valve was created in which there
      would be an angle between the stents so the valve would have a greater orifice
      area. This study was performed to test this valve on bovine aorta to determine
      whether or not there would be a pressure gradient on both sides of the valve. The
      valve created is multiplaned with one stent thought to be seated on the aortic
      annulus for the coronary orifices to receive blood in diastole, whereas the other
      stent is thought to be seated on the ascending aorta obliquely to increase the
      orifice area of the valve. The ascending aorta could be enlarged if necessary. A
      multiplaned valve resembling the valve which has two planes was tested on a
      Dacron tube, one side of which was formed with a bovine aorta. Pressure readings
      before and after the bovine aorta was thinned were taken when a 17 L/min flow
      through the tube was maintained. A 65 mmHg mean pressure gradient and a zero
      pressure gradient were produced before and after thinning the bovine aorta. The
      multiplaned mechanical aortic valve produces no gradient if the aorta is elastic.
      This valve can solve the gradient problem in aortic valve surgery because the
      aorta is a living and elastic tissue.

PMID- 15858946
TI  - Restoration of normal coronary flow with tirofiban by intracoronary
      administration for no-reflow phenomenon after stent deployment.
AB  - No-reflow phenomenon is frequently observed during percutaneous coronary
      intervention in patients with acute coronary syndrome. It may jeopardize
      hemodynamic status or result in ischemic chest pain in these patients. Currently,
      there is no adequate solution for this problem. We report our experience with an
      acute coronary syndrome patient who developed no-reflow phenomenon associated
      with ST segment elevation and shock after percuteneous coronary balloon
      dilatation and stent deployment. Intracoronary administration of tirofiban
      immediately restored the coronary flow of the target vessel, and the disastrous
      condition reversed. Our experience suggests that intracoronary administration of
      tirofiban can be considered as an option in case of no-reflow phenomenon during
      percutaneous coronary intervention.

PMID- 15858947
TI  - A case of recurrent chest pain with reversible left ventricular dysfunction and
      ST segment elevation on electrocardiogram.
AB  - There is a syndrome consisting of acute infarction-like symptoms and ECG
      findings, and transient left ventricular apical ballooning without epicardial
      coronary artery obstruction. A 67-year-old female admitted to our hospital
      because of severe anterior chest pain was diagnosed as having this syndrome.
      Since stenotic, spastic, or occlusive sites were not found in epicardial coronary
      arteries by emergency cardiac catheterization, we speculated coronary
      microvasculature involvement in the pathophysiology of the event. Four weeks
      later in a drug-free condition, there was no significant epicardial coronary
      vasospasm by intracoronary acetylcholine administration (IC-ACh). The average
      peak flow velocity (APFV) of the left coronary artery (LCA) was measured using
      the Doppler flow wire method. Under maximal dilatation of the epicardial LCA by
      intracoronary nitroglycerin administration, IC-ACh was again performed taking
      into consideration that the change in APFV in response to IC-ACh reflects a
      coronary microvascular response to it. In the nonischemic control subjects, basal
      APFV increased to 296+/-29% (n = 24) of the basal value after IC-ACh. In this
      patient, although IC-ACh did not cause vasospasm in epicardial LCA, APFV was
      decreased to 54% of its basal value. After administration of a Ca antagonist and
      KATP opener, she had no chest symptoms and was discharged from the hospital. In
      2003, she forgot to take her medication for 3 days and then experienced a sudden
      recurrence of the same type of attack. She started her medication again and her
      symptoms disappeared. Three weeks later, she underwent an assessment of the
      coronary microvascular response to ACh with medicine. Her APFV after ACh
      increased to 177% of the basal value.

PMID- 15858948
TI  - Left ventricular apical aneurysm as a consequence of diffuse type congenital
      nonfamilial supravalvular aortic stenosis in a 30-year-old female.
AB  - Congenital nonfamilial supravalvular aortic stenosis (SVAS) is relatively rare,
      its diffuse type being the least common. We present a 30-year-old woman with
      diffuse SVAS complicated with left ventricular apical aneurysm. We believe that
      subtle left ventricular myocardial ischemia or infarction and long-lasting severe
      pressure overload to the apical chamber caused LV apical aneurysm in our case.
      Acquired LV apical aneurysm secondary to supravalvular aortic stenosis, in the
      absence of atherosclerotic coronary artery disease and hypertrophic obstructive
      cardiomyopathy, has not been described before.

PMID- 15858949
TI  - Left ventricular diverticulum in two adult patients.
AB  - Left ventricular diverticulum is a rare congenital anomaly. In the adult
      population, the incidence was reported to be 0.26% in nonselected patients who
      underwent cardiac catheterization. Diverticula are usually localized near the
      apex and most often involve the inferior or anterior parietal walls of the left
      ventricle. In this report, two cases with congenital left ventricular
      diverticulum are presented, and the pathophysiologic, diagnostic, and therapeutic
      approaches of this cardiac malformation are discussed.

PMID- 15858950
TI  - A critical increase in right-to-left shunt after acute myocardial infarction in a
      68-year-old male with tetralogy of Fallot.
AB  - A male patient with tetralogy of Fallot accompanied by aortic regurgitation had
      maintained sufficient exercise capacity for a number of decades with the status
      of acyanotic tetralogy of Fallot. When he was 67 years old, he suffered a
      posterior wall acute myocardial infarction and direct percutaneous coronary
      angioplasty successfully revascularised the target lesion in the left circumflex
      artery. However, a few months after the onset of the myocardial infarction, his
      shortness of breath became clinically significant and was associated with
      increased right-to-left shunt and increased right ventricular end-diastolic
      pressure, as well as hypoxia. At 68 years old, therefore, total corrective repair
      of the tetralogy with replacement of the aortic and pulmonary valves was
      performed. The patient was asymptomatic after the successful operation. This
      report suggests that coronary artery disease can be one of the potential factors
      in inducing critical hemodynamic changes in aging patients with congenital heart
      disease, especially those who have a shunt between the right and left chambers.
      The unique clinical course is described with some discussion of the repair of
      tetralogy in adults.

PMID- 15858951
TI  - Control of suture hole bleeding after aortic valve replacement by application of
      BioGlue during circulatory arrest.
AB  - Bleeding from suture holes in aortic valve replacement (AVR) may represent a
      difficult problem especially if the aortic wall is friable. We describe a case in
      which suture hole bleeding after AVR was present at the posterior aortic wall
      close to the pulmonary artery. Following several attempts to suture the leak
      using felt pledget armed prolene sutures, deep hypothermic circulatory arrest was
      induced and BioGlue in combination with Tabotamp was applied for successful
      sealing of the bleeding source.

PMID- 15858952
TI  - Incidence of autism spectrum disorders: changes over time and their meaning.
AB  - AIM: Several reviews have noted a huge increase in the rate of diagnosed autism
      spectrum disorders. The main aims of this paper are: 1) to use published
      empirical findings to consider whether the rise reflects a true increase in
      incidence, as distinct from the consequences of better ascertainment and a
      broadening of the diagnostic concept; and 2) to consider how epidemiological data
      may be used to test hypotheses about possible causal influences, using MMR and
      thimerosal as examples. METHODS: Search of the literature for studies with a
      large epidemiological base population, systematic standardized screening, a focus
      on an age group for which diagnostic assessments are reliable and valid, and
      diagnosis by trained professionals using high-quality research assessments. Also,
      search of a broader literature to consider the evidence from all epidemiological
      studies with respect to the hypothesized causal effect of MMR and thimerosal on
      autism spectrum disorders. RESULTS: The true incidence of autism spectrum
      disorders is likely to be within the range of 30-60 cases per 10 000, a huge
      increase over the original estimate 40 years ago of 4 per 10000. The increase is
      largely a consequence of improved ascertainment and a considerable broadening of
      the diagnostic concept. However, a true risk due to some, as yet to be
      identified, environmental risk factor cannot be ruled out. There is no support
      for the hypothesis for a role of either MMR or thimerosal in causation, but the
      evidence on the latter is more limited. CONCLUSION: Progress in testing
      environmental risk hypotheses will require the integration of epidemiological and
      biological studies.

PMID- 15858953
TI  - How much glutamate is toxic in paediatric parenteral nutrition?
AB  - AIM: To discuss a hypothesis regarding the impact and possible side effects of
      glutamate in paediatric parenteral nutrition. RESULTS: Published evidence
      suggests that the arcuate nucleus, which is a potent site of leptin action, is
      severely damaged by elevated glutamate levels. Early administration of glutamate
      (GLU) to the neonatal rat disrupts the hypothalamic signalling cascade of leptin
      action. CONCLUSION: We are concerned that GLU-containing parenteral nutrition may
      not only increase the risk of hypothalamic damage in neurosurgical patients with
      an impaired blood-brain barrier, and in patients with periventricular
      leukomalacia, but may also permanently damage the arcuate nucleus neurones in the
      very immature infant. This may result in later impairment of feeding regulation,
      obesity, hyperleptinaemia, and other symptoms that characterize the "thrifty
      phenotype" and the dysmetabolic syndrome. We strongly suggest reconsidering the
      recommended daily allowances of amino acids, particularly the use of GLU, in
      current paediatric parenteral nutrition.

PMID- 15858954
TI  - Is there any role for protein hydrolysates to premature newborns?
AB  - The use of hydrolysed cow's milk formula seems to increase beyond what is
      recommended based on evidence regarding allergy-preventive effect. Infants born
      preterm are sometimes given such formulas without proven effect. CONCLUSION: If
      the use of hydrolysed cow's milk formula is based on allergy-preventive aspects,
      evidence-based recommendations should be followed.

PMID- 15858955
TI  - Is screening ultrasound of the urinary tract indicated in infants with
      hypertrophic pyloric stenosis?
AB  - AIM: Few retrospective studies have evaluated infants with hypertrophic pyloric
      stenosis (HPS) for associated urological anomalies. They have led to
      contradictory conclusions. The aim of this study was to evaluate the incidence of
      urinary tract anomalies in infants with HPS and to establish the clinical
      significance of this association. METHODS: One hundred and twenty-two infants
      (100 boys) who underwent pyloromyotomy between 1992 and 2002 were prospectively
      evaluated. Screening ultrasound (Us) of the urinary tract was performed in 107
      infants, while 15 did not attend their ultrasound appointment. RESULTS: Renal
      ultrasound was abnormal in 4 (4%) of 107 screened patients with HPS. Three
      patients were found to have mild hydronephrosis and, in one patient, a small,
      normal kidney was detected. Two patients with hydronephrosis had Us follow-up and
      the third patient underwent Tc-99 mercaptoacetyl triglycine (MAG 3) scan. In all
      three patients, the hydronephrosis resolved completely on follow-up scan.
      CONCLUSION: The incidence of abnormal renal ultrasound in children with HPS is
      similar to the reported incidence of 3-6% determined with routine ultrasound
      screening of healthy newborns. The abnormalities detected were not clinically
      relevant and did not require surgical intervention. We do not recommend screening
      of the urinary tract in infants with HPS.

PMID- 15858956
TI  - Long-chain polyunsaturated fatty acids and neurological developmental outcome at
      18 months in healthy term infants.
AB  - AIM: Previously, we found a beneficial effect of 2 mo supplementation of infant
      formula with long-chain polyunsaturated fatty acids (LC-PUFA) on neurological
      condition at 3 mo in healthy term infants. The aim of the present follow-up study
      was to evaluate whether the effect on neurological condition persists until 18
      mo. METHODS: A prospective, double-blind, randomized control study was conducted.
      Three groups were formed: a control (CF; n = 169), an LC-PUFA-supplemented (LF; n
      = 146) and a breastfed (BF; n = 159) group. Information on potential confounders
      was collected at enrolment. At the age of 18 mo, neurodevelopmental condition was
      assessed by the age-specific neurological examination of Hempel and the Bayley
      scales. The Hempel assessment resulted in a clinical neurological diagnosis, a
      total optimality score and a score on the fluency of motility. The Bayley scales
      resulted in mental and psychomotor developmental indices. Attrition at 18 mo was
      5.5% and non-selective. Multivariate regression analyses were carried out to
      evaluate the effect of type of feeding while adjusting for confounders. RESULTS:
      None of the children had developed cerebral palsy and 23 (CF: n = 8; LF: n = 10;
      BF: n = 5) showed minor neurological dysfunction. The groups did not show
      statistically significant differences in clinical neurological condition,
      neurological optimality score, fluency score, and the psychomotor and mental
      development indices. Multivariate analysis confirmed that there was no effect of
      type of feeding on neurological condition. CONCLUSION: This study indicates that
      the beneficial neurodevelopmental effect of 2 mo LC-PUFA supplementation in
      healthy term infants can not be detected at the age of 18 mo.

PMID- 15858957
TI  - Carotid artery intima-media thickness and angiotensin-converting enzyme gene
      polymorphism in the offspring of parents with premature stroke.
AB  - AIM: To determine some common cardiovascular risk factors, alterations in the
      measurements of intima-media thickness (IMT) and the distribution of the
      angiotensin-converting enzyme (ACE) polymorphism in children of parents with
      premature stroke, and to investigate the cardiovascular risk of these children
      and the potential need for some preventive measures. METHODS: A family history of
      cardiovascular disease represents a cardiovascular risk factor in the offspring.
      This association has not yet been clearly determined for cerebrovascular
      accidents. New technology allows us to investigate the risk for cardiovascular
      disease at an early presymptomatic stage. We applied the measurement of IMT of
      carotid arteries by ultrasound imaging and the determination of the ACE
      insertion/deletion (I/D) polymorphism in blood to evaluate the predisposition for
      cerebrovascular disease in the offspring of patients with previous stroke. We
      investigated 58 subjects whose parents had experienced a cerebrovascular accident
      before the age of 45 y and compared them with a matched control group whose
      parents had not suffered a stroke. RESULTS: The results of IMT at various sites
      of the carotid arteries and the genotype distribution of the ACE gene were not
      significantly different between the study group and the control group. In
      addition, no differences were found in the serum levels of lipid fractions or
      other biochemical variables. CONCLUSION: We conclude that determination of the
      carotid IMT and of the ACE I/D polymorphism do not permit discrimination of the
      cardiovascular risk in children of parents with or without premature stroke.

PMID- 15858958
TI  - Determination of the six major human herpesviruses in cerebrospinal fluid and
      blood specimens of children.
AB  - AIM: To detect and differentiate six major human herpesviruses in the
      cerebrospinal fluid (CSF) and blood of children by polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). METHODS: We synthesized two
      pairs of primers in the well-conserved regions of the DNA polymerase gene in
      human herpesviruses. One pair was designed to amplify cytomegalovirus (CMV),
      Epstein-Barr virus (EBV), herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2),
      and the other pair to amplify varicella-zoster virus (VZV) and human herpesvirus
      6 (HHV-6) by PCR. Virus species identification was achieved by restriction enzyme
      digestion with BamHI and BstUI. Ninety-eight CSF and 75 blood specimens were
      analysed by this technique. At the same time, all blood specimens were also
      examined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Thirteen (13.3%)
      of 98 CSF specimens and 26 (34.7%) of 75 blood specimens were positive for
      herpesvirus DNA in this PCR assay. Only 10 (13.3%) of the blood specimens were
      positive in ELISA for virus-IgM antibody. Sensitivity, specificity, positive
      predictive value (PPV) and negative predictive value (NPV) of PCR in detecting
      herpesvirus infections compared with ELISA were 100% (10/10), 75.4% (49/65),
      38.5% (10/26) and 100% (49/49), respectively. These results indicate that the
      positive rate of PCR was significantly higher than that of ELISA (p < 0.05). The
      herpesvirus type of these positive specimens was rapidly detected using
      restriction enzyme digestion with BamHI and BstUI. CONCLUSIONS: PCR-RFLP is a
      specific, sensitive and accurate technique for the identification of herpesvirus
      infections in the CSF and blood of children.

PMID- 15858959
TI  - Effects of Saccharomyces boulardii in children with acute diarrhoea.
AB  - AIM: Certain probiotic agents, e.g. Lactobacillus GG, have shown efficacy in
      clinical trials for the treatment of acute childhood diarrhoea, but few studies
      have examined the effect of Saccharomyces boulardii. We evaluated the effect of
      S. boulardii in children with acute diarrhoea. METHODS: Two hundred children were
      randomized to receive S. boulardii in a granulated form in a daily dose of 250 mg
      (S. boulardii group) or placebo (placebo group) for 5 d. Clinical and demographic
      characteristics on admission were similar between the study groups. RESULTS: The
      medians of the average stool frequency after the second day of the treatment were
      significantly lower in the S. boulardii group than in the placebo group (p =
      0.003). The duration of diarrhoea significantly reduced in the S. boulardii group
      compared with the placebo group (4.7 vs 5.5 d, p = 0.03). The effect of S.
      boulardii on watery diarrhoea became apparent after the second day of the
      treatment. The duration of hospital stay was shorter in the S. boulardii group
      than in the placebo group (2.9 vs 3.9 d, p < 0.001). Four children from the
      placebo group versus only one child from the S. boulardii group had persisting
      diarrhoea. CONCLUSION: The placebo-controlled study suggested that S. boulardii
      significantly reduced the duration of acute diarrhoea and the duration of
      hospital stay. S. boulardii seems to be a promising agent for the amelioration of
      the course of acute diarrhoea in children when used therapeutically.

PMID- 15858960
TI  - Lack of correlation between fatty acid oxidation disorders and haemolysis,
      elevated liver enzymes, low platelets (HELLP) syndrome?
AB  - AIM: Fatty acid beta-oxidation defects comprise a heterogeneous group of
      disorders that may precipitate acute life threatening metabolic crises
      particularly during catabolic episodes. Several studies have demonstrated a
      possible association between fatty acid beta-oxidation defects, including long
      chain 3-hydroxyacyl-CoA dehydrogenase deficiency and severe pregnancy
      complications. However, the precise percentage of women with haemolysis, elevated
      liver enzymes, low platelets (HELLP) syndrome associated with foetal fatty acid
      beta-oxidation defects is not known. METHODS: We carried out a multicentre
      retrospective study on 88 infants, born to women with HELLP syndrome.
      Acylcarnitine profiles from blood dried on filter paper cards were analysed by
      tandem mass spectrometry for the diagnosis of fatty acid beta-oxidation defects.
      In addition, we screened for the common long-chain 3-hydroxyacyl-CoA
      dehydrogenase deficiency mutation using a standard restriction fragment length
      polymorphism polymerase chain reaction method. RESULTS: None of the infants
      studied carried the common long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
      mutation. There was no evidence of fatty acid beta-oxidation defects, including
      long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, as expected by
      unremarkable acylcarnitine profiles, while three infants with fatty acid beta
      oxidation defects were diagnosed in the control group. CONCLUSIONS: Neither
      foetal long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, including
      heterozygosity for the common long-chain 3-hydroxyacyl-CoA dehydrogenase
      deficiency mutation, nor fatty acid beta-oxidation defects in general are a major
      risk factor for HELLP syndrome in Austria.

PMID- 15858961
TI  - Cytomegalovirus transmission to extremely low-birthweight infants through breast
      milk.
AB  - AIM: To determine the incidence, timing and clinical significance of acquired
      postnatal cytomegalovirus (CMV) in extremely low-birthweight (ELBW) infants.
      METHODS: Prospective, longitudinal surveillance study. ELBW infants were
      recruited in the first week of life. Maternal blood was tested for CMV-specific
      IgG antibodies. Weekly urine samples were obtained from infants for CMV culture
      and rapid antigen testing. Data were collected regarding clinical course and
      breast milk intake. RESULTS: Of 181 eligible infants, 119 infants, born to 101
      mothers, were enrolled. Eighty of the 101 mothers had their serum checked for CMV
      status. Seventy percent of those tested were seropositive for CMV. Of the 65
      infants born to seropositive mothers, 94% received breast milk during their
      hospital stay. Complete urine collection was obtained in 92 infants. CMV was
      cultured from the urine of only four infants, all of whom were born to
      seropositive mothers. Only one of these four infants was symptomatic. The range
      at which CMV was first detected was between 48 and 72 postnatal days of age.
      CONCLUSIONS: Despite a very high CMV seropositivity rate in mothers of ELBW
      infants, and the previously reported high rate of CMV excretion into breast milk,
      the incidence of postnatal CMV transmission was extremely low in our study.

PMID- 15858962
TI  - Extreme hyperbilirubinaemia in term and near-term infants in Denmark.
AB  - AIM: To determine the incidence amongst infants born at term or near-term of
      extreme hyperbilirubinaemia, i.e., with a serum concentration of unconjugated
      bilirubin exceeding the limit above which an exchange transfusion was indicated
      according to the authorized guidelines. METHOD: The investigation period covered
      2 y, 1 January 2000 to 31 December 2001, and included all infants born alive at
      term or near-term in Denmark. All infants with extreme hyperbilirubinaemia
      admitted to paediatric departments were recorded. RESULTS: Thirty-two infants
      developed extreme hyperbilirubinaemia, i.e., an incidence of 25 per 100 000. The
      maximum total serum bilirubin concentration (TSB) was 492 (385-689) micromol/I
      (median (range)). The median value of the exchange transfusion limits was 450
      micromol/l. Twelve infants had signs and symptoms of central nervous system
      involvement; 11 had acute bilirubin encephalopathy phase-1 symptoms; and one had
      phase-2 symptoms. Nineteen infants developed extreme hyperbilirubinaemia during
      primary admission to the maternity ward or neonatal department; the others after
      having been discharged. There was no difference in maximum TSB between those
      infants not discharged from hospital and those infants admitted to hospital from
      home. Maximum TSB appeared latest amongst those infants admitted from home (p <
      0.01), and these more often had signs and symptoms of central nervous system
      involvement (p < 0.05). Ten infants were of non-Caucasian extraction. Less than
      half of all Danish mothers receive both verbal and written information after
      birth on jaundice in the infant. CONCLUSION: Twenty-five per 100 000 infants born
      at term or near-term developed extreme hyperbilirubinaemia, the majority of them
      whilst in hospital. Infants admitted from home more often had signs and symptoms
      of central system involvement.

PMID- 15858964
TI  - Seasonality of invasive Candida infection in neonates.
AB  - AIM: To evaluate season of birth as a risk factor for the development of invasive
      Candida in our population of preterm low-birthweight infants. METHODS:
      Retrospective identification of Candida-positive blood or cerebrospinal fluid
      (CSF) cultures in infants < 32 wk over an 8-y period. RESULTS: There were 1400
      admissions of infants < 32 wk gestation, of whom 52 (3.7%) developed invasive
      Candida infection. Thirty-eight of 52 (73%) occurred during the months September
      to February. CONCLUSIONS: It may be appropriate to consider seasonal associations
      when targeting selective antifungal chemoprophylaxis.

PMID- 15858963
TI  - In vivo spectroscopy of jaundiced newborn skin reveals more than a bilirubin
      index.
AB  - AIM: The aims of this study were to improve the algorithms for calculating a
      transcutaneous bilirubin index (TcB), to follow the bilirubin concentrations
      during phototherapy and to evaluate possible changes in skin optical parameters
      such as pigmentation and erythema during phototherapy. METHOD: Reflectance
      measurements were performed on 51 jaundiced newborns, of which 10 were subjected
      to phototherapy. The measurements were collected with a diode array
      spectrophotometer with an integrating sphere accessory, and a TcB was calculated
      from the measured spectra using algorithms based on diffusion theory. The
      newborns' birthweights were > or = 2000 g and their gestational age was > or =
      35.5 wk. They had no substantial illnesses, and no newborns were submitted to the
      study until their second day. Heel prick blood samples were analysed for total
      serum bilirubin (Sbr) by the diazo reaction method. Phototherapy equipment was
      either an overhead lamp or lightbed. RESULTS: Measurements from the forehead gave
      the best correlation between TcB and Sbr (r = 0.81, p < 0.05). However, during
      phototherapy no significant correlation between TcB and Sbr was observed. A
      correlation (r = 0.45, p < 0.05) was found between phototherapy and melanin index
      obtained from the patients' back. CONCLUSIONS: Reflectance spectroscopy is useful
      in assessing bilirubin concentrations before phototherapy, and can also reveal
      changes in skin parameters such as pigmentation occurring as a result of
      phototherapy.

PMID- 15858965
TI  - Higher urinary excretion of essential amino acids in preterm infants fed protein
      hydrolysates.
AB  - AIM: Protein hydrolysates have been introduced in preterm formulae, but it is not
      clear whether they are needed for the feeding of preterm infants. We designed a
      randomized, controlled trial to test the effects of a preterm formula with
      hydrolysed cow's milk proteins on short-term growth and urinary and plasma amino
      acids levels. METHODS: Infants with a birthweight < or = 1750 g and gestational
      age < or = 34 wk fed a conventional preterm infant formula (formula B) or a
      hydrolysed formula (formula A). Weight was measured daily; length, head
      circumference, mid-arm circumference and total skinfold thickness were measured
      weekly. Blood and urine were analysed for amino acid concentrations at start, 14
      and 28 d. RESULTS: Twenty-one infants met the criteria for randomization. The
      daily feeding volumes were: formula A 172.8 +/- 5.6 vs formula B 170.1 +/- 2.8
      ml/kg/d. Infants fed with formula A showed slower weight gain (17.4 +/- 3.4 vs
      20.5 +/- 3.3 g/kg/d; p = 0.045) and lower mean change in Z-scores for weight (
      0.18 +/- 0.16 vs 0.00 +/- 0.09; p = 0.009) and for head circumference (-0.06 +/-
      0.13 vs 0.06 +/- 0.13; p = 0.049). After 14 d, infants receiving formula A had
      statistically significant higher urinary levels of essential amino acids compared
      to infants receiving formula B. CONCLUSION: Our results support the hypothesis of
      less nutritional value of hydrolysed versus conventional preterm formulae. Higher
      renal excretion of essential amino acids may be one of the mechanisms involved.
      These findings must be confirmed by further studies with larger sample sizes and
      protein hydrolysates with different degrees of hydrolysis.

PMID- 15858966
TI  - Early hypocarbia of preterm infants: its relationship to periventricular
      leukomalacia and cerebral palsy, and its perinatal risk factors.
AB  - AIM: To clarify clinical interactions between early hypocarbia, periventricular
      leukomalacia (PVL) and cerebral palsy of preterm infants. METHODS: Serial
      measurements of PaCO2 using arterial blood samples at 3, 6, 12, 24 and 48 h of
      life were performed for 115 very-low-birthweight infants admitted between 1995
      and 1999. Severe early hypocarbia, defined when at least two of five PaCO2 values
      showed 3.3 kPa or less, was observed in eight infants (hypocarbia group). Preterm
      PVL was diagnosed by serial ultrasonographic examinations and cranial magnetic
      resonance imaging, and subsequently classified into early-onset PVL diagnosed
      within 14 d, or late-onset PVL after 14 d. Perinatal risk factors for early
      hypocarbia were investigated from the mothers' records and interviews with
      obstetricians. RESULTS: The average birthweight in the hypocarbia group was
      significantly smaller than that in the control group (p < 0.01). The occurrence
      of PVL in the hypocarbia group was not different from that in the control group.
      Early hypocarbia was significantly related to late-onset PVL (p < 0.001), but not
      related to early-onset PVL. The incidence of cerebral palsy in the hypocarbia
      group was significantly higher than that in the control group (p < 0.001).
      Multivariate analysis showed that both low birthweight and number of maternal
      previous abortions were predictive for early hypocarbia. CONCLUSION: Early
      hypocarbia of preterm infants in our hospital was significantly associated with
      both cerebral palsy and late-onset PVL, but not with early-onset PVL. The
      background of the three clinical events, early hypocarbia, PVL, and cerebral
      palsy, may not be identical in human newborns.

PMID- 15858967
TI  - Lung function in immature baboons with respiratory distress syndrome receiving
      early caffeine therapy: a pilot study.
AB  - AIM: The cardiopulmonary effects of early caffeine therapy in surfactant-treated
      immature baboons were measured. METHODS: Nine 125-d (term = 185 d) baboons
      receiving caffeine citrate at 1 and 12 h age as part of a pilot study on the use
      of nasal CPAP at 24 h were compared to six untreated animals destined for
      prolonged ventilator support. All received surfactant prior to their first breath
      and again at 6 h age. Serial physiologic and ventilatory parameters were
      recorded. Lung mechanics were measured by body plethysmography. Data were
      compared from 1 through 24 h age. RESULTS: There were no between-group
      differences in any study variables prior to caffeine therapy at 1 h age. Airway
      resistance (RA) was significantly lower in caffeine-treated compared to non
      caffeine-treated animals at 12 and 24 h age [median (range)12 h: 47 (35-107) cm
      H2O/l/s to 135 (120-259) cm H2O/l/s; and 24 h: 93(60-137) cm H2O/l/s to 211 (86
      235) cm H2O/l/s; p < 0.05]. Respiratory system compliance (CRS) was higher in
      caffeine-treated compared to non-caffeine-treated animals at 18 and 24 h age
      [median (range) 18 h: 0.60 (0.29-1.58) ml/cm H2O/kg to 0.39 (0.33-0.46) ml/cm
      H2O/kg; and 24 h: 0.68 (0.36-1.20) ml/cm H2O/kg to 0.36 (0.33-0.55) ml/cm H2O/kg;
      p < 0.05]. Ventilatory efficiency index and arterial/alveolar ratio significantly
      improved in caffeine-treated animals over the 24-h study period (p < 0.05,
      repeated measures ANOVA). CONCLUSIONS: In this pilot study, early caffeine
      treatment, combined with prophylactic surfactant therapy, was associated with
      better lung function during the initial 24 h of life. This combined approach may
      facilitate earlier extubation or prophylactic efforts to support infants on nasal
      CPAP. Randomized, controlled investigation is warranted.

PMID- 15858968
TI  - Pattern of drug prescription for children under the age of four years in a
      population in Greenland.
AB  - AIM: To provide knowledge of drug prescription patterns in general and of
      antibiotics in particular, and number of consultations and diagnoses leading to
      prescriptions among children aged 0-4 y in the Arctic. METHODS: A population
      based cohort of children aged 0-4 y, living in Sisimiut, the second largest town
      in Greenland, was followed from August 1996 to December 1998. Information on
      consultations, diagnoses and drug prescriptions was obtained from medical files
      at the local health centre. RESULTS: Among 280 participating children, the mean
      number of consultations per child was 5.64 per year at risk (range 0-17), of
      prescriptions 4.02 per year at risk (range 0-17.2), and of prescribed systemic
      antibiotics per child 1.47 per year at risk (range 0-7.25). Systemic antibiotics
      formed the therapeutic subgroup most often issued for children, constituting
      33.5% of all prescriptions. Of the systemic antibiotics, 50% were broad-spectrum
      penicillins, 34% penicillin V, 14% macrolides and 2% other antibiotics. The most
      frequent diagnoses leading to drug prescription in general as well as to
      prescription of systemic antibiotics were respiratory tract infections,
      accounting for 59% of all prescriptions and 81% of prescriptions of systemic
      antibiotics. Children aged 1/2-1 y of age had the highest prescription rates of
      drugs in general and of systemic antibiotics. CONCLUSIONS: Compared to other
      countries, prescription rates of drugs in general and of systemic antibiotics in
      particular were high. The use of broad-spectrum penicillins was higher than
      recommended in Greenlandic national guidelines, and might be reduced.

PMID- 15858969
TI  - Socio-economic characteristics in children with coeliac disease.
AB  - AIM: To study the relationship between socio-economic factors and coeliac
      disease. METHODS: This study was part of a prospective cohort study of 16 286
      children born from 1 October 1997-1 October 1999 (the ABIS study; All Babies in
      Southeast Sweden). Eight paediatric departments recorded all children with
      coeliac disease in southeast Sweden. Coeliac disease was confirmed through
      biopsy. Socio-economic characteristics (maternal employment, civil status,
      whether parents were born in Sweden, parental education, place of living before
      pregnancy and during pregnancy, crowded living), infant sex, previous siblings,
      parental age and maternal alcohol consumption during pregnancy were analysed
      using logistic regression. All data, except for those related to diagnosis of
      coeliac disease, were obtained through a questionnaire distributed at birth.
      RESULTS: Coeliac disease in the offspring was less common among mothers who had
      worked < 3 mo during pregnancy (odds ratio, OR = 0.29; 95% CI: 0.09-0.94; p =
      0.039). This risk decrease remained after adjustment for confounders (adjusted OR
      = 0.28; 95% CI: 0.09-0.92; p = 0.035). No other socio-economic factor was related
      to coeliac disease. CONCLUSION: This study indicates that most socio-economic
      factors are probably of little importance to the development of coeliac disease.

PMID- 15858970
TI  - Pulmonary haemorrhage and cardiac dysfunction in a neonate with medium-chain acyl
      CoA dehydrogenase (MCAD) deficiency.
AB  - We report on a favourable case of MCAD deficiency (homozygous 985A > G) that
      presented as lethargy, poor feeding, pulmonary haemorrhage and cardiac arrest
      without hypoglycaemia. The cessation of intralipid and the commencement of
      carnitine supplementation were associated with a rapid clinical improvement.
      CONCLUSION: Mild carnitine depletion and secondary impairment of long-chain fatty
      acid metabolism may have contributed to post-asphyxial myocardial dysfunction and
      ventricular arrhythmias. Metabolic disorders must be kept in mind as a
      differential diagnosis in acutely ill infants, but it must also be emphasized
      that carnitine therapy is not uniformly effective in all MCAD patients.

PMID- 15858971
TI  - Caroli's disease in children: is it commonly misdiagnosed?
AB  - AIM: Caroli's disease is a simple form of intrahepatic bile duct ectasia. It can
      be complicated with the involvement of liver parenchyma and portal hypertension.
      Herein, the difficult management of delayed presentation of Caroli's disease is
      reported. METHODS AND RESULTS: We report on four different forms of clinical
      presentation of Caroli's disease: an infant with fulminant liver failure, a
      teenager with persistent biliary fistula, a boy with hypersplenism in the face of
      portal hypertension and a girl with variceal bleeding. CONCLUSIONS: Caroli's
      disease must be included in the differential diagnosis of cystic lesions in the
      liver. Delayed diagnosis of Caroli's disease is difficult to manage and
      appropriate investigations are warranted before planning a surgical approach.

PMID- 15858972
TI  - Misleading diagnosis of partial N-acetylglutamate synthase deficiency based on
      enzyme measurement corrected by mutation analysis.
AB  - N-acetylglutamate synthase (NAGS) deficiency is a rare urea cycle disorder. Most
      of the patients present in the early neonatal period with severe hyperammonaemia
      and marked neurological impairment. We report on a Turkish family with an index
      patient, who died due to hyperammonemia, and another three siblings, who received
      a prophylactic treatment consisting of arginine hydrochloride, sodium benzoate
      and phenylbutyrate directly after birth. Enzyme measurement in a liver biopsy
      suggested a diagnosis of partial NAGS deficiency in all three siblings.
      Thereafter, N-carbamylglutamate was added to the treatment. None of the patients
      developed hyperammonaemia. After the human NAGS gene was identified, mutation
      analysis revealed that the consanguineous parents and two siblings were
      heterozygous for a private mutation (W484R), whereas the wild-type gene was found
      in the eldest sibling. Therapy was stopped without any deterioration of urea
      cycle function. CONCLUSION: Diagnosis of partial NAGS deficiency based on enzyme
      measurement may be misleading and should be completed by mutation analysis.

PMID- 15858973
TI  - Quantitative predictions to conditions of zwitterionic stacking by transient
      moving chemical reaction boundary created with weak electrolyte buffers in
      capillary electrophoresis.
AB  - This paper develops a novel procedure of quantitative predictions for the on
      column stacking conditions of a zwitterionic analyte by a moving chemical
      reaction boundary (MCRB) in capillary electrophoresis (CE). The procedure
      concerns the choice of the weak acidic running and alkaline sample buffers and
      the velocity design of MCRB created with the two buffers. Based on the theory of
      MCRB, the theoretical computations are performed. From the computations, the
      following two predictions are refined for the stacking conditions of zwitterion.
      (1) The zwitterion velocity in the acidic buffer should be greater than that of
      MCRB moving toward the cathode, or the zwitterion cannot be well stacked by the
      MCRB. (2) The gap between pH values of the acidic and alkaline sample buffers
      ought to comprise the isoelectric point (pI) of zwitterion to be stacked; namely,
      there exists the relation of pH (acidic buffer) < pI < pH (sample). The
      predictions are quantitatively proved by the experiments of zwitterionic stacking
      with two kinds of MCRBs. In addition, the experiments also show the tightly
      stacked peak of zwitterion existing in the process of MCRB, but not after the
      MCRB. The theoretical and experimental results hold obvious significances to
      other zwitterion (such as peptide and protein) on-column stacking in CE.

PMID- 15858974
TI  - PepNovo: de novo peptide sequencing via probabilistic network modeling.
AB  - We present a novel scoring method for de novo interpretation of peptides from
      tandem mass spectrometry data. Our scoring method uses a probabilistic network
      whose structure reflects the chemical and physical rules that govern the peptide
      fragmentation. We use a likelihood ratio hypothesis test to determine whether the
      peaks observed in the mass spectrum are more likely to have been produced under
      our fragmentation model than under a model that treats peaks as random events. We
      tested our de novo algorithm PepNovo on ion trap data and achieved results that
      are superior to popular de novo peptide sequencing algorithms. PepNovo can be
      accessed via the URL http://www-cse.ucsd.edu/groups/bioinformatics/software.html.

PMID- 15858976
TI  - Chasing equilibrium: measuring the intrinsic solubility of weak acids and bases.
AB  - A novel procedure is described for rapid (20-80 min) measurement of intrinsic
      solubility values of organic acids, bases, and ampholytes. In this procedure, a
      quantity of substance was first dissolved at a pH where it exists predominantly
      in its ionized form, and then a precipitate of the neutral (un-ionized) species
      was formed by changing the pH. Subsequently, the rate of change of pH due to
      precipitation or dissolution was monitored and strong acid and base titrant were
      added to adjust the pH to discover its equilibrium conditions, and the intrinsic
      solubility of the neutral form of the compound could then be determined. The
      procedure was applied to a variety of monoprotic and diprotic pharmaceutical
      compounds. The results were highly repeatable and had a good correlation to
      available published values. Data collected during the procedure provided good
      diagnostic information. Kinetic solubility data were also collected but provided
      a poor guide to the intrinsic solubility.

PMID- 15858975
TI  - Influence of chemical kinetics on postcolumn reaction in a capillary Taylor
      reactor with catechol analytes and photoluminescence following electron transfer.
AB  - Postcolumn derivatization reactions can enhance detector sensitivity and
      selectivity, but their successful combination with capillary liquid
      chromatography has been limited because of the small peak volumes in capillary
      chromatography. A capillary Taylor reactor (CTR), developed in our laboratory,
      provides simple and effective mixing and reaction in a 25-microm-radius
      postcolumn capillary. Homogenization of reactant streams occurs by radial
      diffusion, and a chemical reaction follows. Three characteristic times for a
      given reaction process can be predicted using simple physical and chemical
      parameters. Two of these times are the homogenization time, which governs how
      long it takes the molecules in the analyte and reagent streams to mix, and the
      reaction time, which governs how long the molecules in a homogeneous solution
      take to react. The third characteristic time is an adjustment to the reaction
      time called the start time, which represents an estimate of the average time the
      analyte stream spends without exposure to reagent. In this study, laser-induced
      fluorescence monitored the extent of the postcolumn reaction (reduction of
      Os(bpy)3(3+) by analyte to the photoluminescent Os(bpy)3(2+)) in a CTR. The
      reaction time depends on the reaction rates. Analysis of product versus time data
      yielded second-order reaction rate constants between the PFET reagent, tris(2,2'
      bipyridine)osmium, and standards ((ferrocenylmethyl)trimethylammonium cation and
      p-hydroquinone) or catechols (dopamine, epinephrine, norepinephrine, 3, 4
      dihydroxyphenylacetic acid. The extent of the reactions in a CTR were then
      predicted from initial reaction conditions and compared to experimental results.
      Both the theory and experimental results suggested the reactions of catechols
      were generally kinetically controlled, while those of the standards were
      controlled by mixing time (1-2 s). Thus, the extent of homogenization can be
      monitored in a CTR using the relatively fast reaction of the reagent and p
      hydroquinone. Kinetically controlled reactions of catechols, however, could be
      also completed in a reasonable time at increased reagent concentration. A
      satisfactory reactor, operating at 1.7 cm/s (2 microL/min) velocity with solutes
      having diffusion coefficients in the 5 x 10(-6) cm2/s range, can be constructed
      from 8.0 cm of 25-microm-radius capillary. Slower reactions require longer
      reaction times, but theoretical calculations expect that a CTR does not broaden a
      chromatographic peak (N = 14 000) from a 100-microm-capillary chromatography
      column by 10% if the pseudo-first-order rate constant is larger than 0.1 s(-1).

PMID- 15858977
TI  - Templating of multiple ligand metal ion complexation sites in 8-hydroxyquinoline
      modified silica sol-gel materials investigated by in situ Raman spectroscopy.
AB  - Metal ion templating in a sol-gel synthesis is used to develop multiligand 8
      hydroxyquinoline binding sites in porous silica structures. The acid-base
      equilibria and the metal ion binding equilibria and stoichiometry of these
      materials are investigated by in situ Raman spectroscopy. This technique is
      capable of resolving spectral responses of the free ligand and its acid-base
      forms along the monomeric and dimeric ligand complexes with Cu2+. The proton
      transfer equilibrium constants and first ligand binding equilibrium constant to
      Cu2+ for the metal ion-templated silica are equivalent to surface-immobilized 8HQ
      on silica gel. The second ligand binding constant to Cu2+, however, is comparable
      to the first ligand binding constant, which differs from free-solution behavior,
      where an order of magnitude smaller value is expected. The free energy available
      for binding the second ligand within the templated material is comparable to the
      first ligand, probably due to the nearly optimal location of the second ligand
      for binding, based on the templating that is done during this synthesis. The
      metal ion concentration responses of sol-gels prepared with varying amounts of
      metal ion during the syntheses were also tested, and the results indicate control
      over the fraction of templated binding sites.

PMID- 15858978
TI  - Development of a quantitative method for the analysis of tobacco-specific
      nitrosamines in mainstream cigarette smoke using isotope dilution liquid
      chromatography/electrospray ionization tandem mass spectrometry.
AB  - An improved method has been developed for the determination of the four major
      tobacco-specific nitrosamines (TSNA) in mainstream cigarette smoke. The new
      method offers decreased sample preparation and analysis time as compared to
      traditional methodologies. This method uses isotope dilution liquid
      chromatography coupled to a tandem mass spectrometer with electrospray ionization
      and is significantly more sensitive than traditional methods. It also shows no
      evidence of artifactual formation of TSNA. Sample concentrations were determined
      for four TSNA in mainstream smoke using two isotopically labeled TSNA analogues
      as internal standards. Mainstream smoke was collected on an industry standard 44
      mm Cambridge filter pad, extracted with an aqueous buffer solution, and analyzed
      without further sample cleanup. This method has been validated through intra- and
      interlaboratory studies and has shown excellent recoveries, sensitivity, and
      repeatability. The limits of detection of each TSNA varied from 0.01 to 0.1
      ng/mL, and the linear calibration range of the instrument in sample matrix
      spanned 0.5-200 ng/ mL, which allowed for the determination of the TSNA levels in
      cigarettes with a wide range of deliveries. Data are also reported from two
      commercially available industry reference cigarettes and show excellent agreement
      and reproducibility over a six-month time period (n > 50).

PMID- 15858979
TI  - VUV single-photon ionization ion trap time-of-flight mass spectrometer for on
      line, real-time monitoring of chlorinated organic compounds in waste incineration
      flue gas.
AB  - In this work, a sensitive and robust vacuum ultra-violet (VUV) single-photon
      ionization (SPI) ion trap time-of-flight mass spectrometer (VUV-SPI-IT-TOFMS) for
      on-line, realtime monitoring of chlorinated organic compounds in waste
      incineration flue gas has been newly developed. The fragment-free SPI technique
      with 121.6-nm VUV lamp irradiated by a microwave generator and the quadrupole ion
      trap to accumulate and select analyte ions were combined with a reflectron time
      of-flight mass spectrometer to detect chlorinated organic compounds at trace
      level. This measuring system was tuned up to detect dioxins precursors with the
      aim at an application to monitoring trace level toxic substances in flue gases
      from incinerator furnaces. As a result, this technology has made it possible to
      analyze trichlorobenzene (T3CB), a dioxin precursor, in 18 s with a sensitivity
      of 80 ng/m3-N (10 pptv) using the selective accumulation of analyte substances
      and separation of interfering substances in the ion trap. Moreover, the first
      field test of the continuous monitoring T3CB in an actual waste incineration flue
      gas had been done for 7 months. The results show that this system has an
      exceeding robust performance and is able to maintain the high sensitivity in
      analyzing T3CB for long months of operation.

PMID- 15858980
TI  - 15N/14N position-specific isotopic analyses of polynitrogenous amino acids.
AB  - 15N/14N isotope ratios are widely used to study processes and systems involving
      amino acids. Nitrogen isotope fractionation in biological processes occurs
      primarily at sites of bond-breaking and formation; the finest discrimination for
      "isotopic fingerprinting" and studies of isotopic fluxes is thus obtained at the
      position-specific level. While there are numerous reports of natural
      intramolecular carbon isotope variability, there are no literature reports of
      15N/14N position-specific isotopic analysis (N-PSIA) of biologically relevant
      molecules. We report a methodology for high-precision N-PSIA of four
      polynitrogenous alpha-amino acids (asparagine, glutamine, lysine, histidine) and
      the first survey of natural intramolecular 15N/14N in these biomolecules.
      Selective liberation of N-atoms from multiple commercial standards of each parent
      amino acid was achieved by an appropriate enzymatic reaction or by acid
      hydrolysis. 15N/14N measurements were performed on N-ethoxycarbonyl ethyl ester
      derivatives of the parent amino acids and their analogues by gas chromatography
      combustion isotope ratio mass spectrometry, and the average precision for
      replicate injections was found to be SD(delta15N) = 0.3%. Position-specific
      delta15N values of the parent amino acid were directly observed or indirectly
      calculated using mass balance. The average precision obtained for directly
      measured positions was SD(delta15N) = 0.2-0.4%. The average precision for
      indirectly obtained positions was SD(delta15N) = 0.6-1.3% as a result of
      propagation of errors. Enrichment in the side chain-N with respect to the peptide
      N was observed in nearly all of the amino acid sources, most notably in
      asparagine (average delta delta(side-peptide) = + 11%), which may be indicative
      of its method of production. In some cases, it was possible to distinguish
      commercial sources by N-PSIA that could not be distinguished at the compound
      specific level.

PMID- 15858981
TI  - Effect of the surface heterogeneity of the stationary phase on the range of
      concentrations for linear chromatography.
AB  - The range of sample sizes within which linear chromatographic behavior is
      achieved in a column depends on the surface heterogeneity of the RPLC adsorbents.
      Two widely different commercial adsorbents were tested, the end-capped XTerra-C18
      and the non-end-capped Resolve-C18. Adsorption isotherm data of caffeine were
      acquired by frontal analysis. These data were modeled and used to calculate the
      adsorption energy distribution (AED). This double analysis informs on the degree
      of surface heterogeneity. The best adsorption isotherm models are the bi-Langmuir
      and the tetra-Langmuir isotherms for XTerra and Resolve, respectively. Their
      respective AEDs are bimodal and quadrimodal distributions. This interpretation of
      the results and the actual presence of a low density of high-energy adsorption
      sites on Resolve-C18 were validated by measuring the dependence of the peak
      retention times on the size of caffeine samples (20-microL volume, concentrations
      10, 1, 0.1, 1 x 10(-2), 1 x 10(-3), 1 x 10(-4), and 1 x 10(-5) g/L). The
      experimental chromatograms agree closely with the band profiles calculated from
      the best isotherms. On Resolve-C18, the retention time decreases by 40% when the
      sample concentration is increased from 1 x 10(-5) to 10 g/L. The decrease is only
      10% for Xterra-C18 under the same conditions. The upper limit for linear behavior
      is 1 x 10(-4) g/L for the former adsorbent and 0.01 g/L for the latter. The
      presence of a few high-energy adsorption sites on Resolve-C18, with an adsorption
      energy 20 kJ/mol larger than that of the low-energy sites while the same
      difference on Xterra is only 5 kJ/mol, explains this difference. The existence of
      adsorption sites with a very high energy for certain compounds affects the
      reproducibility of their retention times and a rapid loss of efficiency in a
      sample size range within which linear behavior is incorrectly anticipated.

PMID- 15858982
TI  - Surface-enhanced Raman spectroscopy substrate composed of chemically modified
      gold colloid particles immobilized on magnetic microparticles.
AB  - In this paper, immobilization of gold colloidal particles onto amine-modified
      magnetic microparticles is demonstrated. Once immobilized, the gold was then
      reacted with pentachlorothiophenol (PCTP) to form a self-assembled monolayer. The
      PCTP-gold colloid on magnetic microparticles was then used to extract naphthalene
      from aqueous samples. A magnet was used to concentrate the microparticles onto
      the side of the sample vial, allowing detection of naphthalene by surface
      enhanced Raman spectroscopy. Using the PCTP-gold colloid on magnetic
      microparticles the limit of detection for naphthalene achieved was 0.3 microg mL(
      1). Multiple extractions can be done with the PCTP-gold colloid on magnetic
      microparticles to further lower the detection limit.

PMID- 15858983
TI  - Extrinsic Fabry-Perot interferometry for noncontact temperature control of
      nanoliter-volume enzymatic reactions in glass microchips.
AB  - Optical fiber extrinsic Fabry-Perot interferometry (EFPI) was investigated as a
      noncontact temperature sensor and utilized for regulating the temperature of
      small-volume solutions in microchips. Interference pattern analysis determined
      the optical path lengths (OPL) associated with reflections from various surfaces
      on or in the microchip, in particular, from gold sputtered on the bottom of a
      microchannel. Since OPL is directly proportional to refractive index, which is
      dependent on solution temperature, the EFPI sensor was capable of noncontact
      monitoring of solution temperature simply from alterations in the measured path
      length. Calibration of the sensor against a thermocouple was performed while
      heating the microchip in a noncontact manner with an IR lamp. The combination of
      EFPI temperature sensor, IR-mediated heating, and air cooling allowed a fully
      noncontact system for small-volume temperature control in microchip structures,
      and its utility was illustrated by optimal digestion of DNA by a temperature
      dependent restriction endonuclease in 320 nL. The functionality and simplicity of
      the microchip EFPI temperature sensor was enhanced by replacing the prebonding
      sputtered gold with a tunable, chemically plated semireflective silver coating
      created in situ after chip fabrication. This provided an 8-fold improvement in
      the lowest detectable temperature change (deltaT = 0.1 degrees C), facilitated
      primarily by enhanced reflection from both the bottom and top surfaces of the
      microchannel. This approach for controlling micro- and nanoscale reactions--with
      heating, cooling, and temperature control being carried out in a completely
      noncontact fashion--provides an accurate and sensitive method for executing
      chemical and biochemical reactions in microchips.

PMID- 15858984
TI  - Near-infrared emission spectrometry based on an acousto-optical tunable filter.
AB  - A spectrometer has been constructed to detect the radiation emitted by thermally
      excited samples in the near-infrared spectral region extending from 1500 to 3000
      nm. The instrument employs an acousto-optical tunable filter (AOTF) made of TeO2
      and attains maximum sensitivity by making effective use of the two diffracted
      beams produced by the anisotropic AOTF. The full exploitation of the transmitted
      power of the monochromatic beams is reported for the first time and became
      possible because the detector does not saturate when employed for the acquisition
      of the weak emission signal in the NIR region, even when exposed to the total
      (nondiffracted) beam. Thus, modulation and lock-in-based detection can be
      employed to find the intensity of the diffracted beams superimposed on the
      nondiffracted beam. The resolution is slighted degraded in view of the small
      (approximately 10 nm) difference in the wavelength diffracted in the ordinary and
      extraordinary beams. The instrument has been evaluated in terms of signal-to
      noise ratio, effect of sample thickness, and excitation temperature and for its
      potential in analytical applications in monitoring high-temperature kinetics, for
      qualitative identification of inorganic solids, for use with a closed cell to
      obtain spectra of species that evaporate at the temperatures (> 150 degrees C)
      necessary for sample excitation, and for quantitative purposes in the
      determination of soybean oil content in olive oil. The feasibility of near
      infrared emission spectroscopy has been demonstrated together with some of its
      advantages over mid-infrared emission spectroscopy, such as greater tolerance to
      sample thickness, suitable signal-to-noise, and its use in the investigation of
      kinetic phenomena and phase transitions at high temperatures.

PMID- 15858985
TI  - Time-resolved NIR spectroscopy for quantitative analysis of intact pharmaceutical
      tablets.
AB  - Near-infrared (NIR) spectroscopy is a useful technique for quantitative
      measurements of intact tablets, but it suffers from limitations due to the fact
      that changes in the physical properties of a sample strongly affect the recorded
      spectrum. In this work, time-resolved transmission NIR spectroscopy was utilized
      to conduct quantitative measurements of intact tablets. The technique enables
      separation of the absorption properties of the sample from the scattering
      properties and can therefore handle changes of the physical parameters of the
      samples in a better way than conventional NIR transmission spectroscopy. The
      experiments were conducted using a pulsed Ti:sapphire laser coupled into a
      nonlinear photonic crystal fiber as light source. The light transmitted through
      the sample was measured by a time-resolving streak camera. A comparison of the
      results from the time-resolved technique with the results from conventional
      transmission NIR spectroscopy was made using tablets containing different
      concentrations of iron oxide and manufactured with different thicknesses. A PLS
      model made with data from the time-resolved technique predicted samples 5 times
      better than a PLS model made data from the conventional NIR transmission
      technique. Furthermore, an improvement to predict samples with physical
      properties outside those included in the calibration set was demonstrated.

PMID- 15858986
TI  - Fraunhofer effect atomic absorption spectrometry.
AB  - The dark lines in the solar spectrum were discovered by Wollaston and cataloged
      by Fraunhofer in the early days of the 19th century. Some years later, Kirchhoff
      explained the appearance of the dark lines: the sun was acting as a continuum
      light source and metals in the ground state in its atmosphere were absorbing
      characteristic narrow regions of the spectrum. This discovery eventually spawned
      atomic absorption spectrometry, which became a routine technique for chemical
      analysis in the mid-20th century. Laboratory-based atomic absorption
      spectrometers differ from the original observation of the Fraunhofer lines
      because they have always employed a separate light source and atomizer. This
      article describes a novel atomic absorption device that employs a single source,
      the tungsten coil, as both the generator of continuum radiation and the atomizer
      of the analytes. A 25-microL aliquot of sample is placed on the tungsten filament
      removed from a commercially available 150-W light bulb. The solution is dried and
      ashed by applying low currents to the coil in a three-step procedure. Full power
      is then applied to the coil for a brief period. During this time, the coil
      produces white light, which may be absorbed by any metals present in the
      atomization cloud produced by the sample. A high-resolution spectrometer with a
      charge-coupled device detector monitors the emission spectrum of the coil, which
      includes the dark lines from the metals. Detection limits are reported for seven
      elements: 5 pg of Ca (422.7 nm); 2 ng of Co (352.7 nm); 200 pg of Cr (425.4 nm);
      7 pg of Sr (460.7 nm); 100 pg of Yb (398.8 nm); 500 pg of Mn (403.1 nm); and 500
      pg of K (404.4 nm). Simultaneous multielement analyses are possible within a 4-nm
      spectral window. The relative standard deviations for the seven metals are below
      8% for all metals except for Ca (10.7%), which was present in the blank at
      measurable levels. Analysis of a standard reference material (drinking water)
      resulted in a mean percent recovery of 91%. This report attempts to give an
      historical perspective on the development of a novel atomic spectrometer based on
      the Fraunhofer effect.

PMID- 15858987
TI  - Thickness measurement of nanoscale polymer layer on polymer substrates by
      attenuated total reflection infrared spectroscopy.
AB  - For the first time, attenuated total reflection (ATR)-Fourier transform infrared
      (FT-IR) spectroscopy was utilized to measure the thickness (d0) of a nanoscale
      polymer layer on polymer substrate with significant credibility. First, a
      mathematical formula, A/A0 = 1 - 2d0/ d(p), was derived based on a self-defining
      subsection function (where d(p) was defined as depth of penetration of ATR and A
      and A0 were defined as the absorption band area of the characteristic functional
      group only contained in bulk substrate with a thin polymer layer attachment and
      the same group in blank substrate, respectively). On the mathematical model,
      through changing incidence angles, a series of values of A (A0) and corresponding
      d(p) were obtained, and when plotting A/A0 versus 2/d(p), d0 was obtained as the
      slope. With polystyrene (coating)/olypropylene (substrate) as a model system, we
      obtained the relevant values (d0). Comparing the results with the values of
      practical coating thickness (calculation and TEM observation), we found that this
      method was able to characterize well the thickness of a thin polymer layer on a
      polymer substrate in the range from 10 to 110 nm. Errors in the measurement were
      given and analyzed. Furthermore, this method was well applied in the thickness
      measurement of a polyacrylamide graft layer on a polypropylene film surface. The
      effect of pressure in the ATR technique on the coating thickness measurement was
      also discussed. In comparison with other methods such as XPS, SEM, TEM, and AFM,
      this approach based on a universal ATR technique was very convenient and fast.
      This method is expected to widen the application of the ATR-FT-IR technique and
      stimulate the further development of many fields such as surface self-assembly
      and surface functionlization.

PMID- 15858988
TI  - A reactive poly(ethylene glycol) layer to achieve specific surface plasmon
      resonance sensing with a high S/N ratio: the substantial role of a short
      underbrushed PEG layer in minimizing nonspecific adsorption.
AB  - A reactive poly(ethylene glycol) (PEG)-brushed layer was constructed on a surface
      plasmon resonance (SPR) sensor chip using a heterobifunctional PEG possessing an
      acetal group at one end and a mercapto group at the other end (alpha-acetal-omega
      mercapto-PEG). The density of the PEG brushed layer substantially increased with
      repetitive adsorption/rinse cycles of the PEG on the sensor chip, allowing
      dramatic reduction of nonspecific protein adsorption. Notably, formation of a
      short, filler layer of PEG (2 kDa) in the preconstructed longer PEG brushed layer
      (5 kDa) achieved almost complete prevention of nonspecific protein adsorption.
      The acetal group located at the distal end of the tethered PEG was converted to
      an aldehyde group by the acid treatment, followed by the installation of biocytin
      hydrazide through Schiff base formation. SPR sensing of streptavidin was done
      with a very high S/N ratio even in a proteinous medium using the biotinylated PEG
      (5 kDa) tethered chip with an inert filler layer of short PEG (2 kDa).
      Furthermore, the specific affinity of streptavidin for the biotinylated PEG was
      highly influenced by the length of the filler PEG and was significantly reduced
      when the length of the filler PEG was longer than that of the biotinylated PEG.
      This result clearly revealed the substantial importance of the steric factor on
      biospecific interaction at the distal end of tethered PEG on the sensor surface.

PMID- 15858989
TI  - Stable isotope labeling of entire Bacillus atrophaeus spores and vegetative cells
      using bioaerosol mass spectrometry.
AB  - Single vegetative cells and spores of Bacillus atrophaeus, formerly Bacillus
      subtilis var. niger, were analyzed using bioaerosol mass spectrometry. Key
      biomarkers were identified from organisms grown in 13C and 15N isotopically
      enriched media. Spore spectra contain peaks from dicipolinate and amino acids.
      The results indicate that compounds observed in the spectra correspond to
      material from the spore's core and not the exosporium. Standard compounds and
      mixtures were analyzed for comparison. The biomarkers for vegetative cells were
      clearly different from those of the spores, consisting mainly of phosphate
      clusters and amino acid fragments.

PMID- 15858990
TI  - Ordered silicon nanocavity arrays in surface-assisted desorption/ionization mass
      spectrometry.
AB  - We report here a simple method to generate ordered nanocavity arrays on a Si
      wafer and use it in surface-assisted laser desorption/ionization mass
      spectrometry (SALDI-MS). A close-packed SiO2 nanosphere array was first deposited
      on a low-resistivity Si wafer using a convective self-assembly method. The
      nanoparticle array was then used as a mask in a reactive ion etching (RIE)
      process to selectively remove portions of the Si surface. Subsequent sonication
      removed those physically adsorbed SiO2 nanoparticles and exposed an ordered
      nanocavity array underneath. The importance of this approach is its capability of
      systematically varying surface geometries to achieve desired features, which
      makes detailed studies of the impacts of surface features on the
      desorption/ionization mechanism feasible. We demonstrated that the in-plane width
      and out-of-plane depth of the cavities were adjustable by varying etching times,
      and the intercavity spacing was controllable by varying the number of particle
      layers deposited. MS detection of small peptides on these substrates showed
      comparable sensitivity to conventional porous Si substrates (DIOS, desorption/
      ionization on porous silicon). The desorption and ionization efficiency of these
      roughened surfaces exhibited a nonmonotonic relationship to the increased total
      surface area. Several possible factors contributing to the observed phenomenon
      are speculated upon. The application of this arrayed surface in metabolite
      detection of Arabidopsis thaliana root extracts is also demonstrated.

PMID- 15858991
TI  - Stable and functional immobilization of histidine-tagged proteins via multivalent
      chelator headgroups on a molecular poly(ethylene glycol) brush.
AB  - We present a generic approach for immobilizing oligohistidine-tagged proteins
      with high stability and homogeneous functionality onto glass-type surfaces.
      Multivalent chelator heads (MCH) carrying two and three nitrilotriacetic acid
      (NTA) moieties were coupled with controlled surface concentration to glass
      surfaces premodified with an ultrathin two-dimensional polymer brush of a
      bifunctional poly(ethylene glycol). Low roughness and lateral homogeneity of
      these surfaces were confirmed by AFM and fluorescence microscopy, respectively.
      Protein immobilization and interactions at these interfaces were studied by label
      free and fluorescence detection. Oligohistidine-tagged proteins bound
      specifically to NTA loaded with nickel(II) ions and could be eluted with
      imidazole. More than 90% of the immobilized protein preserved its activity. In
      contrast to mono-NTA, immobilized multivalent chelator heads bound oligohistidine
      tagged proteins stoichiometrically and with high stability, even at very low
      chelator surface concentrations. Thus, an excess of the metal chelator sites was
      not necessary, and excessive binding sites could be quantitatively blocked with
      an indifferent protein. As a consequence, increased functional stability of the
      immobilized protein and a substantial reduction in nonspecific adsorption were
      achieved. Binding of histidine-tagged proteins to the MCH-modified surface was
      efficiently blocked by stoichiometric amounts of soluble MCH, and biomolecular
      interaction unbiased by the interaction of the histidine tag to the surface-bound
      MCH was observed. These excellent features and the compatibility with many solid
      phase analytical techniques make this surface chemistry beneficial for functional
      protein analysis.

PMID- 15858992
TI  - Doping of glass with lithium ion.
AB  - Doping of glass with lithium ion can be accomplished by exposing the glass to a
      solution of organic solvent containing a soluble lithium ion salt, such as LiBr
      and a small amount of water. Under such conditions, the activity of solvated Li+
      is very high causing it to partition into the hydrated glass surface. Laser
      induced breakdown spectroscopy and atomic absorption spectroscopy have been used
      to monitor the partitioning between glass and organic phase, respectively.

PMID- 15858993
TI  - Scanning electrochemical microscopy of model neurons: constant distance imaging.
AB  - Undifferentiated and differentiated PC12 cells were imaged with the constant
      distance mode of scanning electrochemical microscopy (SECM) using carbon ring and
      carbon fiber tips. Two types of feedback signals were used for distance control:
      the electrolysis current of a mediator (constant-current mode) and the impedance
      measured by the SECM tip (constant-impedance mode). The highest resolution was
      achieved using carbon ring electrodes with the constant-current mode. However,
      the constant-impedance mode has the important advantages that topography and
      faradaic current can be measured simultaneously, and because no mediator is
      required, the imaging can take place directly in the cell growth media. It was
      found that vesicular release events do not measurably alter the impedance, but
      the depolarizing solution, 105 mM K+, produces a dramatic impedance change such
      that constant-distance imaging cannot be performed during application of the
      stimulus. However, by operating the tip in the constant-height mode, cell
      morphology (via a change in impedance) and vesicular release could be detected
      simultaneously while moving the tip across the cell. This work represents a
      significant improvement over previous SECM imaging of model neurons, and it
      demonstrates that the combination of amperometry and constant-impedance SECM has
      the potential to be a powerful tool for investigating the spatial distribution of
      neurotransmitter release in vitro.

PMID- 15858994
TI  - Calibration effects for laser-induced breakdown spectroscopy of gaseous sample
      streams: analyte response of gas-phase species versus solid-phase species.
AB  - The effects of analyte phase on the calibration response for laser-induced
      breakdown spectroscopy is investigated for a range of carbon species. Significant
      differences in the atomic emission signal from carbon were observed when
      comparing calibration streams of gas-phase and submicrometer-sized solid-phase
      carbon species. The resulting calibration curve slopes varied by a factor of 8
      over a comparable range of atomic carbon concentrations for five different
      analyte sources, while the plasma electron density and temperature remained
      essentially constant. The current findings challenge a widely held assumption
      that complete dissociation of constituent species within a highly energetic laser
      induced plasma results in independence of the analyte atomic emission signal on
      the analyte source. A physical model of the plasma-analyte interaction is
      proposed that provides a framework to account for the observed dependence on the
      physical state of the analyte.

PMID- 15858995
TI  - In vivo monitoring of fluorescent nanosphere delivery in anesthetized rats using
      an implantable fiber-optic microprobe.
AB  - An implantable needle-type fiber-optic microprobe was constructed to monitor in
      vivo fluorescent substances in anesthetized rats. This fiber-optic microprobe was
      composed of coaxial optical fibers that were catheterized using a thin-wall tube
      of stainless steel (o.d. approximately 400 microm; i.d. approximately 300
      microm). When the fiber-optic microprobe was placed in solutions containing
      various concentrations of fluorescent nanospheres (20 nm), either in the presence
      or in the absence of 10% Lipofundin acting as an optical phantom, we observed
      nanosphere concentration-dependent responses of the fluorescence intensity. The
      microprobe was then implanted into the livers and brains of anesthetized rats to
      monitor the in situ extravasation of preadministered fluorescent nanospheres from
      vasculature following the hepatic and cerebral ischemic insults. Both types of
      ischemic insults showed immediate increases in fluorescent intensities when 20-nm
      fluorescent nanosphere were administered, but neither ischemic insult induces
      such an increase when we administered 1000-nm fluorescent nanospheres. Additional
      experiments can be performed to further narrow the size range of the increase in
      blood vessel permeability following ischemic insult; such "size" information may
      be valuable when formulating drugs for optimal local delivery. Although a wide
      variety of fluorescent substances are used intensively for in vitro biological
      studies, the in vivo and in situ monitoring of these substances is studied much
      less often, probably because of difficulties in the efficient assembly of
      miniaturized fiber optics to detect the relatively weak fluorescence signal
      arising within such a turbid medium as tissue. To our knowledge, the use of our
      implantable fiber-optic microprobe is the first minimally invasive technique
      capable of investigating the "size window" of vascular permeability for the in
      vivo delivery of nanospheres in both ischemic livers and brains.

PMID- 15858996
TI  - Redox mediation and photomechanical oscillations involving photosensitive
      cyclometalated Ru(II) complexes, glucose oxidase, and peroxidase.
AB  - Intact photosensitive cyclometalated RuII derivatives of 2-phenylpyridine or N,N
      dimethylbenzylamine cis-[Ru-(C approximately N)(LL)X2]PF6 [C approximately N = o
      C6H4-py or o-C6H4CH2NMe2; LL = 1,10-phenanththroline (phen), 2,2'-bipyridine
      (bpy), or 4,4'-Me2-2,2'-bipyridine (Me2bpy); X = MeCN or pyridine (py)] are
      efficient mediators of glucose oxidase (GO) from Aspergillus niger and
      horseradish peroxidase (HRP). Their redox potentials in an aqueous buffer are in
      the range 0.15-0.35 V versus SCE, and the rate constants for the oxidation
      GO(red) (where red indicates reduced) by the electrochemically generated RuIII
      species equal (1.7-2.5) x 10(6) M(-1) s(-1) at pH 7 and 25 degrees C. The redox
      potentials of all complexes decrease cathodically by 0.4-0.6 V upon irradiation
      by visible light because of the photoinduced solvolysis of acetonitrile or py
      ligands. These in situ generated species display an even better mediating
      performance with HRP, although their behavior toward GO is different. The loading
      of a ruthenium unit into the protein interior brings about large catalytic
      currents in a self-assembled system GO-Ru-D-glucose. The estimated rate constant
      for intramolecular electron transfer from FADH2 of the active site at RuIII,
      k(intra), equals 4.4 x 10(3) s(-1). This suggests that the distance between the
      redox partners is around 19 A. The value of 21 A was obtained through the docking
      analysis of a possible closest-to-FAD localization of a Ru-containing fragment
      derived from the irradiated complex cis-[Ru(o-C6H4-py)-(phen)(MeCN)2]PF6. The
      operational stability of the GO-Ru assemblies depends on the nature of complex
      used, the highest being observed for cis-[Ru(o-C6H4-py)(Me2-bpy)(MeCN)2]PF6 (2).
      UV-vis studies of interaction of 2 with GO revealed photomechanical oscillations
      in the system GO-Ru-D-glucose. When irradiated complex 2 is mixed with GO and D
      glucose, the absorbance at 510 nm increases because of the enzymatic reduction of
      RuIII to RuII. The absorbance drops rapidly and then increases as in the first
      cycle after shaking the reaction solution. Many cycles are possible, and the rate
      of absorbance increase does not depend on a cycle number. A plausible mechanism
      of the oscillations is presented.

PMID- 15858997
TI  - Dispersion of solute by electrokinetic flow through post arrays and wavy-walled
      channels.
AB  - In this work, we simulate electrokinetically driven transport of unretained
      solute bands in a variety of two-dimensional spatially periodic geometries (post
      arrays as well as sinuous/varicose channels), in the thin Debye layer limit.
      Potential flow fields are calculated using either an inverse method or a Schwarz
      Christoffel transform, and transport is modeled using a Monte Carlo method in the
      transformed plane. In this way, spurious "numerical diffusion" transverse to
      streamlines is completely eliminated, and streamwise numerical diffusion is
      reduced to arbitrary precision. Late-time longitudinal dispersion coefficients
      are calculated for Peclet numbers from 0.1 to 3162. In most geometries, a Taylor
      Aris-like scaling law for the dispersion coefficient D(L)/D(L0) = 1 + Pe2/alpha
      underpredicts dispersion when Pe approximately O(alpha1/2) (here D(L0) is the
      effective axial diffusion coefficient in the periodic geometry). A two-parameter
      correlation widely used in the porous media literature, D(L)/D(L0) = 1 +
      Pe(n)/alpha, agrees slightly better, but much better agreement can be obtained
      using a new quadratic form: D(L)/D(L0) = 1 + Pe/alpha1 + Pe2/alpha2. A quasi
      universal relationship for stream-wise dispersion is offered that predicts 96% of
      the simulation data to within a factor of 2 in all geometries studied. Comparison
      with previous work shows that in circular post arrays, the dispersion coefficient
      for electrokinetic flow is a factor of 3-10 less (depending on Pe and relative
      post size) than for pressure-driven flow.

PMID- 15858998
TI  - Nucleic acid-based fluorescence sensors for detecting proteins.
AB  - We report here development of a rapid, homogeneous, aptamer-based fluorescence
      assay ("molecular beacons") for detecting proteins. The assay involves protein
      induced coassociation of two aptamers recognizing two distinct epitopes of the
      protein. The aptamers contain short fluorophore-labeled complementary "signaling"
      oligonucleotides attached to the aptamer by non-DNA linker. Coassociation of the
      two aptamers with the protein results in bringing the two "signaling"
      oligonucleotides into proximity, producing a large change of fluorescence
      resonance energy transfer between the fluorophores. We used thrombin as a model
      system to provide proof-of-principle evidence validating this molecular beacon
      design. Thrombin beacon was capable of detecting the protein with high
      selectivity (also in complex biological mixtures), picomolar sensitivity, and
      high signal-to-background ratio. This is a homogeneous assay requiring no sample
      manipulation. Since the design of molecular beacons described here is not limited
      to any specific protein, it will be possible to develop these beacons to detect a
      variety of target proteins of biomedical importance.

PMID- 15858999
TI  - Surface plasmon resonance/mass spectrometry interface.
AB  - A strategy for combining surface plasmon resonance (SPR) biomolecular interaction
      analysis, and matrix-assisted laser desorption/ionization mass spectrometry
      (MALDI-MS) is reported. Both techniques are highly complementary but need
      separate optimization to improve their individual specificity and sensitivity.
      Sensor surfaces that are optimal for kinetic analysis are not well suited for
      MALDI-MS and vice versa. In addition, the transfer of analyte from SPR to MS is
      crucial and often accompanied by sample loss. To address both of these points, a
      bifunctional SPR fluid cell was constructed where optimized surfaces can be used
      for binding studies and MS simultaneously with regard to the special need of each
      technique. The setup guarantees that the SPR and the loading experiment for MS
      are performed at identical conditions. A removable pin carries the affinity
      surface-bound analyte to the mass spectrometer so that handling is minimized,
      avoiding analyte elution. Functionalized transfer pins can also be used
      independently of SPR for microaffinity capture-MS.

PMID- 15859000
TI  - Tin-diffused glass slab waveguides locally covered with tapered thin TiO2 films
      for application as a polarimetric interference sensor with an improved
      performance.
AB  - Common soda lime slide glass substrates made by floating molten glass on the
      surface of molten tin contain a tin-diffused layer that is demonstrated to be a
      low-loss polarization-insensitive slab optical waveguide. In this study, such a
      tin-diffused waveguide was locally covered with a tapered thin TiO2 film to form
      a composite structure in which the zeroth-order transverse electric (TE0) and
      magnetic (TM0) modes are spatially separated from each other. This feature
      enables the composite structure to serve as a highly sensitive polarimetric
      interferometer. Moreover, a negligible modal birefringence of tin-diffused
      waveguides offers the polarimetric interferometer an improved performance
      relative to those fabricated earlier using single-mode potassium ion-exchanged
      glass waveguides. In situ detection of both the protein adsorption and a small
      change in refractive index of liquid was accomplished using the tin-diffused
      waveguide-based polarimetric interferometer. With horse heart myoglobin,
      adsorption from aqueous solution less than 0.125 monolayer coverage can cause the
      interferometer to yield a phase-difference change of delta phi = 2pi.

PMID- 15859001
TI  - Use of paired, bonded NdFeB magnets in redox magnetohydrodynamics.
AB  - Bonded neodymium-iron-boron (NdFeB) permanent magnets in a paired configuration
      were successfully used to control mass transport in redox-based,
      magnetohydrodynamics (MHD). Control of fluid flow based on magnetic fields has
      potential for use in portable lab-on-a-chip (LOAC) and analytical devices. Bonded
      magnets, composed of magnetic powder and organic binder materials, are less
      expensive and easier to fabricate and pattern than electromagnets and sintered
      permanent magnets, which have been previously used in MHD studies on
      electrochemical systems. The ability to pattern bonded magnets near and around
      the electrodes is expected to allow for better control over the magnetic field
      distribution and solution flow. Current was generated at an 800-microm-radius
      platinum disk electrode in a solution of 0.06 M nitrobenzene and 0.5 M tetra-n
      butylammonium hexafluorophosphate in acetonitrile. Increases in limiting current
      in the presence of the magnetic field, which indicate enhancement in mass
      transport, for sintered (210+/-14%, N = 4, where B(r) = 1.23 T and magnetic field
      strength is 0.55 T) and bonded (94+/-8%, N = 4, where B(r) = 0.41 T and magnetic
      field strength is 0.20 T) magnets, were similar to those obtained using an
      electromagnet with the same magnetic flux densities. The magnetic field strength
      and not the magnet type is important in controlling fluid flow, which is
      encouraging for integration of bonded permanent magnets into LOAC devices.

PMID- 15859002
TI  - Sample preparation of organic liquid for off-site analysis of chemical weapons
      convention related compounds.
AB  - Off-site analysis of chemical warfare agents (CWAs) and related compounds plays a
      key role in the verification program of the Chemical Weapons Convention (CWC).
      The analysis results, aiming toward unambiguous identication of compounds, depend
      on the type of sample preparation method. Development of milder sample
      preparation methods, which offer good recoveries and do not alter the structure
      of analytes, is highly desirable. Organic liquid with high hydrocarbon background
      is a frequently encountered challenge in off-site analysis and in official
      proficiency tests conducted by OPCW. Sample cleanup procedures, namely, solvent
      exchange followed by cooling and liquid-liquid extraction were studied to
      eliminate the hydrocarbons from organic liquid. Acetonitrile, a polar aprotic
      solvent, was effectively used to remove the background in both methods, and
      recoveries of spiked CWAs by the two techniques were between 69 and 99%.

PMID- 15859003
TI  - Moving beyond traditional UV-visible absorption detection: cavity ring-down
      spectroscopy for HPLC.
AB  - We describe the use of liquid-phase continuous-wave cavity ring-down spectroscopy
      for the detection of an HPLC separation. This technique builds on earlier work by
      Snyder and Zare using pulsed laser sources and improves upon commercially
      available UV-visible detectors by a factor of up to 50. The system employs a
      compact doubled-diode single-mode continuous-wave laser operating at 488 nm and a
      previously described Brewster's-angle flow cell. Ring-down time constants as long
      as 5.8 micros were observed with liquid samples in a 0.3-mm path length cell. The
      baseline noise during an HPLC separation was only 2 x 10(-7) absorbance units
      (AU) peak to peak, as compared to 1 x 10(-5) AU for a state-of-the-art commercial
      UV-visible detector.

PMID- 15859004
TI  - Preconcentration of volatile organics on self-assembled, carbon nanotubes in a
      microtrap.
AB  - This paper reports the self-assembly of carbon nanotubes (CNTs) on the inside
      wall of a steel capillary to fabricate a microtrap for the adsorption/desorption
      of trace organics. The microtrap functioned as a nanoconcentrator and an injector
      for gas chromatography (GC). The CNTs were deposited as a thin film by catalytic
      chemical vapor deposition from either CO or C2H4 as the precursor. The sorbent
      film synthesized from C2H4-CVD (CVD = chemical vapor deposition) had higher CNT
      density and thus was a stronger sorbent. In general, the CNT microtraps showed
      high-capacity adsorption and fast quantitative desorption, and the process showed
      excellent precision. This study demonstrates that CNT films can be deposited
      quite easily in a steel capillary for use in different analytical applications,
      and CNT films can perform as efficiently as packed-bed carbon sorbents.

PMID- 15859005
TI  - Miniaturized cavity ring-down detection in a liquid flow cell.
AB  - A novel method for applying cavity ring-down spectroscopy in the liquid phase,
      compatible with LC analyses, is presented. The core of the setup is a home-built
      cavity ring-down flow cell (cell volume 12 microL) that is constructed using a
      silicon rubber spacer, which is clamped leak-tight between two high-reflectivity
      mirrors. The mirrors are in direct contact with the liquid flow, which provides
      for a small path length and short ring-down times. Inside the cavity there are no
      windows, reflection losses, or Brewster angles to be considered. Due to the small
      size of the presented cavity geometry, the setup can be implemented in
      conventional-size LC apparatuses. With a flow injection setup, a detection limit
      of 2.5 nM was obtained for Crystal Violet in ethanol, and the linear dynamic
      range of the system is at least 2 orders of magnitude. The method has the
      potential to become a powerful alternative for commercial LC UV/visible
      absorbance detectors.

PMID- 15859006
TI  - A method for calculating the spring constant of atomic force microscopy
      cantilevers with a nonrectangular cross section.

PMID- 15859007
TI  - Polymer-enzyme composite biosensor with high glutamate sensitivity and low oxygen
      dependence.

PMID- 15859008
TI  - Stable dioxetane precursors as selective trap-and-trigger chemiluminescent probes
      for singlet oxygen.

PMID- 15859009
TI  - Genotoxicity of environmental agents assessed by the alkaline comet assay.
AB  - Generation of DNA damage is considered to be an important initial event in
      carcinogenesis. A considerable battery of assays exists for the detection of
      different genotoxic effects of compounds in experimental systems, or for
      investigations of exposure to genotoxic agents in environmental or occupational
      settings. Some of the tests may have limited use because of complicated technical
      setup or because they only are applicable to a few cell types. The single cell
      gel electrophoresis (comet) assay is technically simple, relatively fast, cheap,
      and DNA damage can be investigated in virtually all mammalian cell types without
      requirement for cell culture. The aim of this thesis was to evaluate the comet
      assay as a genotoxicity test in genetic toxicology of environmental agents,
      encompassing both experimental animal models and biomonitoring. The comet assay
      detects strand breaks (SB). The cells are embedded in agarose and lysed,
      generating nucleus-like structures in the gel (referred to as nucleoids).
      Following alkaline electrophoresis, the DNA strands migrate toward the anode, and
      the extent of migration depends on the number of SB in the nucleoid. The
      migration is visualized and scored in a fluorescence microscope after staining.
      Broad classes of oxidative DNA damage can be detected as additional SB if
      nucleoids are incubated with bacterial DNA glycosylase/endonuclease enzymes.
      Oxidized pyrimidines and purines can be detected by incubation with endonuclease
      III and formamidopyrimidine DNA glycosylase, respectively. The animal
      experimental studies indicated that the comet assay was able to detect genotoxic
      effects of diesel exhaust particles in lung tissue, 2-amino-3-methylimidazo[4,5
      f]quinoline (IQ)-induced DNA damage in colon epithelial cells and liver tissue,
      and benzene-induced damage in bone marrow and liver cells. The strength of the
      comet assay was further outlined by application of repair enzymes, indicating no
      oxidative DNA base damage following IQ treatment. High levels of oxidative DNA
      lesions were detected after exposure to benzene or X-ray irradiation. The comet
      assay did not detect DNA damage in colon or liver following ingestion of diets
      containing of high contents of animal fat or sucrose, although other indices of
      DNA damage were found. Determined from the results of a large Japanese study, the
      discrimination between carcinogens and non-carcinogens appears to be similar
      between the comet assay and alkaline elution, which also detects SB. This
      suggests that the comet assay is a reliable genotoxicity test in animal
      experimental systems. In the biomonitoring studies, we investigated the effect of
      common exposures and lifestyle factors (rather than effects of known carcinogens)
      on the level of oxidative DNA damage in mononuclear blood cells of humans. In the
      first study, based on repeated measurements, it was shown that interindividual
      variation and seasonal variation were major determinants for the basal level of
      SB, whereas no effect of age, exercise, or antioxidant intake could be detected.
      The effect of exercise was further investigated under both normoxic and hypoxic
      circumstances, showing a strong effect of hypoxia, and only effect of exercise in
      terms of SB in hypoxia. In a placebo-controlled parallel dietary fruit and
      vegetable (or the corresponding amount of antioxidants) intervention study, no
      effects of the level of oxidative DNA damage or sensitivity to hydrogen peroxide
      were observed. Although this may seem in contrast to other antioxidant
      intervention studies, a critical literature survey of antioxidant intervention
      studies on oxidative DNA damage suggested that well-controlled studies tended to
      show no effect of antioxidant supplementation. In summary, the aggregated data
      from the publications included in this thesis, and other publications
      encompassing the comet assay, indicate that the comet assay is a reliable method
      for detection of DNA damage in tissues of experimental animals. Although not all
      types of genotoxic exposures should be expected to result in DNA damage in
      mononuclear blood cells, the comet assay seems to be a valuable tool for
      detection of genotoxic exposure in humans. The comet assay indicates that DNA
      damage is abundant in mammalian cells and affected by lifestyle and many
      environmental exposures, including diet, exercise, hypoxia, and sunlight.

PMID- 15859010
TI  - Pediatric three-dimensional ultrasound: basics and potential clinical value.
AB  - Three-dimensional ultrasound (3DUS) has become an established modality in some
      specialties; however, it has not gained significant importance in pediatric
      imaging. The aim of this short review article is to demonstrate and discuss
      promising potential applications of 3DUS in pediatric sonography. 3DUS is
      performed using a variety of techniques and devices, generally based on a volume
      reconstruction after the acquisition of a three-dimensional ultrasound (2DUS)
      image series, which is then viewed using various display formats. Based on our
      experience and a literature research, 3DUS appears to be a promising US technique
      for the neonatal brain and pediatric genitourinary tract. Furthermore, some other
      applications, such as 3DUS of the neonatal spinal canal, some soft tissue and
      mucsculo-skeletal queries, and tumor volume assessment, hold promising
      perspectives. 3DUS may reduce the imaging time of the patient, may improve the
      demonstration of complex anatomy, and has been shown to improve volume
      assessment. It furthermore holds the potential to improve standardization and
      documentation, as well as comparison with other sectional imaging. 3DUS also
      appears to be an ideal modality for training and education, as the 3D volume can
      be virtually rescanned at the workstation without the patient's presence. In
      conclusion, we believe that 3DUS is a promising imaging tool also for pediatric
      applications.

PMID- 15859011
TI  - Assessment of hyperacute stroke like symptoms by diffusion-weighted images.
AB  - We assessed the role of diffusion-weighted images in the evaluation of hyperacute
      stroke like symptoms in 18 patients. The volume of infarct measured by diffusion
      weighted imaging (DWI) was correlated with the later computed tomography (CT)
      examinations. DWI had a sensitivity of 92%, specificity of 100%, positive
      predictive value of 100%, and negative predictive value of 86% in detection of
      acute hemorrhagic and ischemic stroke. There is a good correlation with the
      volume of infarct measured by DWI and follow-up CT with a P < .05.

PMID- 15859012
TI  - Assessment of malignancy in gliomas by 3T 1H MR spectroscopy .
AB  - The purpose of this study was to assess clinical 1H MR spectroscopy (MRS) as a
      noninvasive method for evaluating brain tumor malignancy at 3T high-field system.
      Using 3T MRI/MRS system, localized water-suppressed single-voxel technique in
      patients with brain tumor (i.e., gliomas) was employed to evaluate spectra with
      peaks of N-acetyl aspartate (NAA), choline-containing compounds (Cho),
      creatine/phosphocreatine (Cr) and lactate. On the basis of Cr, these peak areas
      were quantitated as a relative ratio. The variation of metabolite measurements of
      the designated region in 10 normal volunteers was less than 10%. Normal ranges of
      NAA/Cr and Cho/Cr ratios were 1.67+/-018 and 1.16+/-0.15, respectively. NAA/Cr
      ratio of gliomas was significantly lower than that of the normal tissues (P=
      .005), but Cho/Cr ratio of gliomas was significantly higher (P= .001). Cho/Cr
      ratio of high-grade gliomas was significantly higher than that of low-grade
      gliomas. The present study demonstrated that the neuronal degradation or loss was
      observed in all gliomas. Higher-grade glioma was correlated with higher Cho/Cr
      ratio, indicating a significant dependence of Cho levels on malignancy of
      gliomas. Our results suggest that clinical 1H MR spectroscopy could be useful to
      predict tumor malignancy.

PMID- 15859013
TI  - Right ventricular dysfunction secondary to acute massive pulmonary embolism
      detected by helical computed tomography pulmonary angiography.
AB  - OBJECTIVE: Acute massive pulmonary embolism causes abrupt pulmonary arterial
      hypertension and right ventricular dysfunction (RVD). Patients with RVD have a
      worse prognosis than those with normal right ventricular function. Consequently,
      recognizing the RVD at the time of pulmonary embolism is useful for risk
      stratification and enables more aggressive therapy. The study compared the
      accuracy of helical computed tomographic (CT) scans with echocardiography in the
      detecting of RVD in patients with acute massive pulmonary embolism. MATERIALS AND
      METHODS: Specifically, this work reviewed the CT pulmonary angiograms of 14
      patients who were positive for acute massive pulmonary embolism during a 52-month
      period. CT scans were reviewed for findings indicating RVD. Scans were considered
      positive for RVD if the right ventricle was dilated or there was leftward shift
      of the interventricular septum. Echocardiographic reports serving as the
      reference standard for the diagnosis of RVD were also reviewed. CT study results
      were then correlated with echocardiography results. RESULTS: Among 14 patients
      with massive pulmonary embolism, echocardiography identified 12 patients having
      RVD, whereas the remaining two patients were negative for RVD. Meanwhile, CT
      correctly identified 11 of 12 patients as having RVD, and was negative for RVD in
      the remaining 3 patients. Correlated with echocardiography, CT scan for RVD
      detection had a sensitivity of 91.6% and a specificity of 100%. CONCLUSIONS: CT
      can accurately detect RVD in patients with acute massive pulmonary embolism.
      However, this result requires confirmation using a larger prospective cohort
      study.

PMID- 15859014
TI  - Inflammatory breast cancer: imaging findings.
AB  - To assess the imaging findings of inflammatory breast cancer, we retrospectively
      analyzed the mammography, ultrasonography, and magnetic resonance imaging (MRI)
      findings of nine patients with inflammatory breast cancer. Inflammatory breast
      cancer showed skin thickening and nipple-areolar swelling on mammography,
      ultrasonography, and MRI. Tumor with lymphatic dilatation on ultrasonography and
      enhancement of thickened skin and parenchyma on MRI can be useful findings in the
      diagnosis of inflammatory breast cancer.

PMID- 15859015
TI  - Stereotactic breast biopsy of noncalcified lesions: a cost-minimization analysis
      comparing 14-gauge multipass automated core biopsy to 14- and 11-gauge vacuum
      assisted biopsy.
AB  - A decision model was used to compare the relative costs of the 14-gauge automated
      gun technique to the 14-gauge and 11-gauge vacuum-assisted techniques for
      stereotactic biopsy of noncalcified breast lesions. Probability and cost
      variables were estimated from clinical experience with 76 automated gun biopsies,
      seventy-eight 14-gauge vacuum-assisted biopsies and thirty-nine 11-gauge vacuum
      assisted biopsies. The 14-gauge automated gun was the preferred strategy from a
      cost standpoint: the 14-gauge vacuum technique was 1.19 times more expensive, and
      the 11-gauge was 1.22 times more expensive.

PMID- 15859016
TI  - Advanced dynamic flow imaging with contrast-enhanced ultrasonography for the
      evaluation of tumor vascularity in liver tumors.
AB  - To examine the usefulness of advanced dynamic flow imaging in diagnosing hepatic
      tumor and in assessing therapeutic effects in patients with hepatocellular
      carcinoma (HCC) and metastatic hepatic tumor, we performed contrast-enhanced
      ultrasonography (US) with Levovist, a microbubble contrast agent. Twenty-two
      patients of 35 HCC nodules infected with hepatitis C virus (HCV) and six patients
      with metastatic liver nodules were studied. They were diagnosed as having HCC or
      metastasis with helical dynamic computed tomography (CT) and/or celiac
      angiography. Tumor vascularities in the early arterial and postvascular phases
      were assessed by real-time scanning of advanced dynamic flow imaging and
      intermittent interval-delay scanning of contrast pulse subtraction imaging with a
      wide-band power Doppler technology. All patients showed hypervascular enhancement
      of HCC on contrast-enhanced US and/or dynamic CT. The advanced dynamic flow could
      be obtained as vascular and perfusion images of hepatic tumors. Tumor
      vascularities, including tumor vessels and parenchymal flow, were able to
      demonstrate in 27 of 29 nodules including 17 patients with 27 HCC nodules and 2
      patients with 2 metastatic nodules before radiofrequency ablation (RFA) treatment
      by the advanced dynamic flow on contrast-enhanced harmonic US. Two nodules gave
      insufficient dynamic flow which were located approximately 12 cm in depth from
      the body surface. The advanced dynamic flow, which was done 7-10 days after RFA,
      indicated disappearance of the tumor vessels in 27 of visible 27 nodules. The
      study on early phase of helical dynamic CT revealed the same results as noted in
      early vascular phase of dynamic flow US. No major complication of RFA procedure
      was noted. The results indicated that contrast-enhanced advanced dynamic flow
      imaging on US clearly depicted intratumoral vascularity in real time and thus it
      is useful to diagnose and assess therapeutic efficacy in patients with HCC and
      metastatic liver tumor.

PMID- 15859017
TI  - MRCP evaluation of biliary system following vagotomy and gastric surgery.
AB  - OBJECTIVE: The aim of this study was to show the usefulness of MR
      cholangiopancreatography (MRCP) in demonstrating biliary system pathologies in
      patients with a history of vagotomy and Billroth II operations. METHODS: The
      hepatobiliary system of eight patients with a history of vagotomy and Billroth II
      operations was evaluated with MRCP. Three-dimensional fast spin-echo technique
      was used at a 1.0-T scanner with following parameters: TR=2857-4615 ms, TE=850
      1117 ms, BW=31.2, FOV=40, 21-28 slices, NEX=0.5, scan time = 90 s. RESULTS: Eight
      patients were evaluated with MRCP. Three patients had cholecystectomy. In one
      patient the gall bladder wall was thickened, accompanied with an irregular,
      unknown filling defect at the level of the fundus. Four of these patients had
      common bile duct stones. Two patients had gallstones and one patient had a stone
      in the common hepatic duct. A capping deformity of the distal common bile duct
      was observed in all of the patients. CONCLUSION: We conclude that MRCP can be
      used effectively for evaluation of biliary system of patients with previous
      history of biliary or gastric operations.

PMID- 15859018
TI  - Postoperative MR findings of the healthy ACL grafts: correlation with second look
      arthroscopy.
AB  - PURPOSE: To evaluate the postoperative MR findings of healthy anterior cruciate
      ligament (ACL) grafts, which were confirmed by second look arthroscopic
      examination. MATERIALS AND METHODS: We evaluated 33 MR scans of 29 patients who
      underwent postoperative MR scans and second look arthroscopic examination (four
      patients underwent postoperative MRI twice) between June 1996 and January 2001.
      There were 18 male and 11 female patients, and their ages ranged from 16 to 59
      years old (mean 29.7). There were 15 cases of autogenous bone-patellar tendon
      bone (BPTB) grafts, 13 cases of autogenous double-loop hamstring grafts, and 1
      case of allogenous BPTB graft. Thirty-three MRIs were divided into three groups
      according to the time interval between operation and postoperative MR
      examination: less than 6 months, 7-12 months, and 13 or more months. The
      following MR findings of ACL grafts--signal intensity, morphology, continuity,
      orientation, and diameter--were analyzed. RESULTS: Increased signal intensity was
      found in 29 ACL grafts (87.7%). The most common pattern of the graft morphology
      was a longitudinal streak-increased signal intensity band (27 cases, 81.8%). A
      partial rupture was seen in nine cases (27.3%) and lax orientation in four cases
      (12.1%). The signal intensity score of the ACL graft tended to decrease with time
      after operation, and the sagittal diameter of the graft tended to increase with
      time after operation. CONCLUSION: The main postoperative MR findings of the
      healthy ACL graft was a longitudinal streak-increased signal intensity band. The
      graft signal intensity seemed to decrease and the sagittal diameter of the graft
      seemed to increase as time passed after operation.

PMID- 15859019
TI  - MRI of epithelioid sarcoma of the thigh.
AB  - A 31-year-old woman with epithelioid sarcoma of the thigh is presented. The
      patient had had a progressively growing mass in her left thigh for 4 months.
      Magnetic resonance imaging (MRI) showed a subcutaneous mass with a central area
      of hypointensity and serpiginous hyperintensity in the peripheral portion. Such
      findings have not been reported before. Histologic findings were compatible with
      epithelioid sarcoma.

PMID- 15859021
TI  - Too low blood cholesterol?

PMID- 15859020
TI  - Metastasis in vertebra mimicking acute compression fractures in a patient with
      osteoporosis: MRI findings.
AB  - Elderly patients who have osteoporosis and a cancer history with backache and
      vertebral fractures are diagnostic challenges. We present a case of an 87-year
      old man who complained of severe low-back pain with radiation to the lower limbs
      and weakness of the lower limbs. The patient had had a fall on a bus 1 month
      before admission. The patient also had a history of colon cancer and had received
      a colostomy 9 years before. In this admission, lumbar spine radiographs showed
      compressive fractures of vertebral bodies at L1 and L3. Magnetic resonance
      imaging (MRI) showed hyperemic change of the L3 marrow with osteonecrosis (fluid
      sign). The ventral thecal sac was slightly compressed due to retropulsion of L3.
      The L1 marrow was normal. Bone densitometry of the calcaneous revealed
      osteoporosis. The patient was then treated by vertebroplasty and bilateral
      foraminotomy of L3 after a diagnosis of acute compressive fracture. On histology,
      there was a metastatic adenocarcinoma arranged in glands and nests in the bone
      and paraspinal soft tissue. On retrospective viewing, an axial gadolinium
      enhanced MRI revealed paraspinal extension of soft tissue at L3, which is highly
      suggestive of metastasis in a vertebra.

PMID- 15859022
TI  - Determination of 17alpha-hydroxyprogesterone in serum by liquid chromatography
      tandem mass spectrometry and immunoassay.
AB  - 17Alpha-hydroxyprogesterone (17OHP) is the most important serum marker for
      congenital adrenal hyperplasia (CAH). 17OHP is usually measured by immunoassay
      but its detection by mass spectrometry (MS) is a potentially superior method. An
      LC-MS (liquid chromatography-mass spectrometry) method was developed which
      utilizes 0.5 ml serum spiked with 6-alpha-methylprednisolone (6-MP) or deuterated
      17OHP (d8-IS) as the internal standard. The samples were extracted with
      ether/ethylacetate, and the extract was evaporated to dryness and analysed by LC
      MS/MS operating in the positive mode after separation on a reversed-phase C18
      column. The calibration curves for analysis of serum 17OHP exhibited consistent
      linearity and reproducibility in the range of 5-250 nmol/l. Interassay CVs were
      8.5 and 9.2% at mean concentrations of 7.9 and 23 nmol/l, respectively. The
      detection limit was 1 nmol/l (signal-to-noise ratio=3). The mean recovery of
      17OHP added to serum ranged from 76 to 89% and that of internal standards from 75
      to 82%. The regression equation for the LC-MS/MS (x) and in-house
      radioimmunoassay (RIA) (y) methods was: y=0.87x+0.26 (r=0.97; n=100) and for a
      commercial RIA it was: y=1.32x+0.02 (r=0.97; n=26).

PMID- 15859023
TI  - Acid base and electrolyte changes after hypertonic saline (7.5%) infusion: a
      randomized controlled clinical trial.
AB  - Hypertonic saline solutions are effective in the treatment of haemorrhagic and
      septic shock, elevated intracranial pressure and perioperative fluid deficits.
      Infusion, however, causes electrolyte and acid-base imbalance. In a randomized
      double-blind study, the effects of a 10-min infusion of 4 ml/kg 7.5% NaCl or 0.9%
      NaCl were evaluated in 14 fasting women before hysterectomy. Venous blood from
      the forearm was collected at baseline, 10, 20, 30, 60 and 120 min after start of
      the infusion for the determination of plasma electrolytes and acid-base balance.
      We found that 1) a median increase in plasma sodium of 11 mmol/l (range 9-13
      mmol/l) and chloride of 14 mmol/l (range 9-16 mmol/l) immediately after the
      infusion followed by a small decrease after 2 h, 2) a minor decrease in plasma
      potassium in relation to the infusion followed by a significant increase of 0.3
      mmol/l (range 0.1-1.4 mmol/l) above baseline after 1 h, 3) a decrease in pH of
      0.05 (range 0.02-0.07) and, finally, 4) a decrease in base excess of 1.9 mmol/l
      (range 0.8-2.7 mmol/l). It is concluded that infusion of 7.5% NaCl in a clinical
      relevant dose increases plasma potassium and causes minor changes in the acid
      base balance in normovolaemic women.

PMID- 15859024
TI  - Serum C-reactive protein in elderly men and women: association with mortality,
      morbidity and various biochemical values.
AB  - OBJECTIVE: The primary aim of this study was to define the distribution and the
      prognostic value of serum C-reactive protein (s-CRP) measured by a high
      sensitivity method in elderly subjects of both genders with special reference to
      the distribution below 10 mg/l. As a secondary aim, a possible gender difference
      of s-CRP was examined. MATERIAL AND METHODS: Baseline s-CRP was described in a
      population-based sample of opposite-sex, twin-pairs (197 F, 189 M available for
      blood-sampling) aged 71-80 years (mean age 74.5 years), considering mortality
      through the next 4 years, morbidity (myocardial infarction, angina pectoris,
      congestive heart failure, arterial hypertension, venous thromboembolism, stroke,
      diabetes, gout, psoriasis, rheumatoid arthritis) before and after blood sampling,
      biochemical values (serum levels of urate, urea, ApoA1, ApoB, folate, FSH, LH,
      oestradiol, progesterone, testosterone, cortisol) and anthropometric measurements
      (body mass index (BMI), circumference of waist, buttocks and hips). RESULTS: The
      level of s-CRP did not deviate substantially from what has been reported for
      younger subjects. Higher values indicated an increased risk of cardiovascular
      morbidity and diabetes in women but not in men. The s-CRP level was associated
      with serum levels of urate, progesterone, folate, ApoA1, ApoB and the quotient
      ApoB/ApoA1 as well as with BMI and waist circumference. CONCLUSIONS: For the 71
      80 years age group, s-CRP below the 80th percentile (4.3 mg/l) seems to have
      prognostic capacity mainly in women. The highest association with mortality as
      well as with cardiovascular diseases, diabetes and rheumatoid arthritis is found
      for s-CRP above 10 mg/l, which is the arbitrary lower level for the earlier
      routine low-sensitivity s-CRP methods. The association of s-CRP with serum urate,
      folate and the ApoB/ApoA1 quotient should be considered.

PMID- 15859025
TI  - How do conventional markers of lipid disorders compare with apolipoproteins?
AB  - Assessment of risk for coronary heart disease (CHD) indicates that apolipoprotein
      B and apolipoprotein A-I and their ratio are efficient predictors, possibly
      superior to hitherto used indicators, i.e. S-Cholesterol, S-Triglycerides, S-HDL
      cholesterol and S-LDL cholesterol. We used the ratio S-Apolipoprotein B/S
      Apolipoprotein A-I as the gold standard to compare the diagnostic performance of
      the other properties based on consecutive routine measurements in patients
      attending primary health-care or a university hospital. The different cut-offs of
      the S-Apolipoprotein B/S-Apolipoprotein A-I ratio that were investigated created
      a prevalence of risk factors that might require intervention in the study group
      between 10 and 77%. The gender difference prompts for a partitioning related to
      the gender, whereas the changes related to age were small and were disregarded.
      The diagnostic sensitivity and specificity were demonstrated in ROC diagrams for
      the studied properties.

PMID- 15859026
TI  - Iron status among 3005 women aged 20-55 years in Central Norway: the Nord
      Trondelag Health Study (the HUNT study).
AB  - OBJECTIVE: To describe the iron status of Norwegian women of fertile age, to show
      the prevalence of iron-deficiency anemia and iron overload, and to demonstrate
      possible factors connected to and/or influencing iron status. MATERIAL AND
      METHODS: The diagnostic criteria were: (a) anemia: hemoglobin (Hb) < 120, < 117,
      or < 115 g/l; (b) depleted iron stores: serum ferritin (SF) < 10 or 12 microg/l;
      iron-deficiency anemia: (a)+(b). Iron overload: SF > or = 110 microg/l. The study
      was conducted in Central Norway where a total of 3005 women aged 20 to 55 years
      were enrolled in a health survey program (the HUNT Study). None of the women were
      pregnant and none had been blood donors in the two previous years. RESULTS:
      Median SF was 31.0 microg/l. Depleted iron stores were present in 10.9 and 15.1%,
      respectively. The Hb 2.5%tile among the iron-replete women was 117 g/l. With this
      cut-off value, anemia was present in 4.7% and iron-deficiency anemia in about 3%.
      Iron overload was present among 5.2%, and homozygous primary hemochromatosis
      among 0.4%. CONCLUSIONS: The prevalence of iron-deficiency anemia was relatively
      low and similar to that found earlier in small groups of Norwegian women. The
      prevalence is comparable with results from other developed countries.

PMID- 15859027
TI  - Inhibition of chemiluminescence by carvedilol in the cell-free system, whole
      human blood and blood cells.
AB  - Carvedilol inhibits luminol-enhanced chemiluminescence of reactive oxygen
      metabolites in vitro. In this study it was found that, in the cell-free system,
      carvedilol dose-dependently decreased chemiluminescence in the following ranking
      order of radicals: hydroxyl radical > hydrogen peroxide > superoxide radical. The
      inhibition of myeloperoxidase was significant with carvedilol concentrations of
      10 and 100 micromol/l and manifested in the concentration-dependent shift of
      chemiluminescence peaks to the right. In whole blood, carvedilol in
      concentrations of 10 and 100 micromol/l significantly inhibited chemiluminescence
      induced by both receptor-bypassing stimuli (A23187, PMA) and receptor-operating
      stimuli (fMLP, OpZ). Carvedilol dose-dependently inhibited chemiluminescence of
      isolated human polymorphonuclear leucocytes in the ranking order of stimuli:
      A23187 > OpZ > fMLP. In the presence of blood platelets, carvedilol did not
      substantially change chemiluminescence induced by fMLP and OpZ, while it was much
      more effective on chemiluminescence stimulated with calcium ionophore A23187.
      This could be the result of the supportive effect of serotonin liberated from
      platelets by A23187.

PMID- 15859028
TI  - Serum lipids, glucose and insulin levels in healthy schoolchildren aged 9 and 15
      years from Central Sweden: reference values in relation to biological, social and
      lifestyle factors.
AB  - BACKGROUND: There is a shortage of reference values for cardiovascular risk
      factors such as serum lipids, glucose and insulin related to biological, social
      and lifestyle factors for Swedish children and adolescents. Such values are
      needed for planning and evaluation of public health activities, and for clinical
      use. DESIGN AND METHODS: Data for this cross-sectional, school-based study were
      collected during a school year (September to May). A random sample of 1137 girls
      and boys aged 9 and 15 years from two locations in central Sweden participated in
      the study, and blood samples were taken from 969 of them. METHODS: Fasting serum
      blood samples were analysed for triglycerides, total cholesterol, high-density
      lipoprotein cholesterol, glucose and insulin. Physical examination included
      measurement of height, weight and pubertal status. Questionnaires provided family
      background data. Total physical activity was measured by accelerometer
      registration. RESULTS: Serum levels differed significantly between age and gender
      groups and were correlated to pubertal status. Neither genetic nor socio-economic
      background nor smoking status influenced the serum levels. Insulin levels were
      elevated in subjects with a body mass index in the highest decentile, compared
      with the levels in the rest of the subjects. The insulin levels were inversely
      associated with total physical activity, and physical activity varied with
      season. CONCLUSIONS: Pubertal status (biological age) should to be considered in
      the interpretation of serum values in schoolchildren rather than chronological
      age. The interpretation of insulin values should include both body mass index and
      physical activity level, and perhaps also season. Previously described regional
      differences in serum lipid levels in Swedish adults seem to be present also in
      children.

PMID- 15859029
TI  - Melatonin does not affect total antioxidant capacity of blood plasma in vitro.
AB  - Although melatonin has been claimed to increase total antioxidant capacity (TAC)
      of blood serum, this does not seem probable in view of the low physiological
      concentrations of this hormone in blood, in relation to other antioxidants. This
      study demonstrates that enrichment of blood plasma with melatonin up to
      micromolar concentrations does not affect TAC in vitro thus excluding any
      significant direct contribution of melatonin to TAC of blood plasma.

PMID- 15859030
TI  - [Nurses as partners].

PMID- 15859031
TI  - [Having a choice--living in the dementia ward].

PMID- 15859032
TI  - [The future of homes for the aged and nursing homes].

PMID- 15859033
TI  - [Experiences in the preventive home visit].

PMID- 15859034
TI  - [Wound care is more than the application of bandages].

PMID- 15859035
TI  - [Farewell to freshly prepared foods? Future systems for large-scale cooking].

PMID- 15859036
TI  - [Health foundations].

PMID- 15859037
TI  - [LIS: a pilot project for mobility for locked-in patients].

PMID- 15859038
TI  - [Eventually it always still comes down to needle stick injuries].

PMID- 15859040
TI  - [Future review].

PMID- 15859039
TI  - [Ten-year performances of nursing insurance].

PMID- 15859041
TI  - [Application interview with an Assessment Center].

PMID- 15859042
TI  - [Ginger gives warmth].

PMID- 15859043
TI  - [Medical visit services].

PMID- 15859044
TI  - [Criticall point in depression. PFLEGE AKTUELL Marz 2005, zum TopThema
      "Depression"].

PMID- 15859045
TI  - [Notes on professional designation. PFLEGE AKTUELL Februar 2005, zu "lhre
      Berufsvertreter im DBfK sind fur Sie da"].

PMID- 15859046
TI  - Commercial insurance vs community-based health plans: time for a policy option
      with clinical emphasis to address the cost spiral.
AB  - The nation continues its ceaseless struggle with the spiraling cost of health
      care. Previous efforts (regulation, competition, voluntary action) have included
      almost every strategy except clinical. Insurers have largely failed in their cost
      containment efforts. There is a strong emerging body of literature that
      demonstrates the relationship between various clinical strategies and reductions
      in utilization and costs. This article describes the organization of health
      services, including integration of delivery and financing systems, at the
      community level as a model that effectively addresses the critical structural
      flaws that have frustrated control of costs. Community-based health plans (CHPs)
      have been developed and have demonstrated viability. The key elements of CHPs are
      a legal organizational structure, a full provider network, advanced care
      management systems, and the ability to assume financial risk. Common
      misconceptions regarding obstacles to CHP development are the complexity of the
      undertaking, difficulty assuming the insurance function, and insured pools that
      are too small to be viable. The characteristics of successful CHPs and 2 case
      studies are described, including the types of advanced care-management systems
      that have resulted in strong financial performance. The demonstrated ability of
      CHPs to establish financial viability with small numbers of enrollees challenges
      the common assumption that there is a fixed relationship between health plan
      enrollment size and financial performance. Organizing the health system at the
      community/regional level provides an attractive alternative model in the health
      reform debate. There is an opportunity for clinical systems and state and federal
      leaders to support the development of community-based integrated delivery and
      financing system models that, among other advantages, have significant potential
      to modulate the pernicious cost spiral.

PMID- 15859047
TI  - The Federal Employees Health Benefits Program: a model for competition in rural
      America?
AB  - CONTEXT: The Medicare Prescription Drug, Improvement, and Modernization Act of
      2003 (MMA) created the Medicare Advantage (MA) program, which promotes the entry
      of private Preferred Provider Organization (PPO) plans into regions that have not
      previously had Medicare managed care plans. The assumption that a competitive
      environment will develop is based on experiences in the Federal Employees Health
      Benefits Program (FEHBP). PURPOSE: The authors test the hypothesis that the FEHBP
      has fostered an environment of competing health plans, especially preferred
      provider organizations (PPOs), in rural areas. METHODS: Data from the US Office
      of Personnel Management are used to quantify the number of FEHBP-certified plans
      in each US county and the number of enrollees in each plan. Data from the Area
      Resource File are used to measure independent variables in multivariate analysis
      to account for the number of FEHBP-certified health plans competing in each US
      county. FINDINGS: While 98% of all counties have at least 3 plans with
      enrollment, in many sparsely populated rural areas, only 1 of the plans is an
      open-enrollment plan (excludes plans for letter carriers). There is a strong
      relationship between the number of FEHBP plans and areas with high population
      counts and high population density. In many counties with low population counts
      (under 3,000), most PPOs are not contracting with the nearest primary care
      provider. CONCLUSIONS: The FEHBP is not a perfect predictor of MA plan activity
      because the MA program does not use the FEHBP approach of certifying regional
      plans that must offer local access. However, the FEHBP experience indicates that
      plans are attracted to areas with high population counts and high population
      density.

PMID- 15859048
TI  - How might the Medicare Prescription Drug, Improvement, and Modernization Act of
      2003 affect the financial viability of rural pharmacies? An analysis of
      preimplementation prescription volume and payment sources in rural and urban
      areas.
AB  - CONTEXT: Passage of the Medicare Prescription Drug, Improvement, and
      Modernization Act of 2003 (MMA) has created interest in how the legislation will
      affect access to prescription drugs among rural beneficiaries. Policy attention
      has focused to a much lesser degree on the implications of the MMA for the
      financial viability of rural pharmacies. PURPOSE: This article presents
      descriptive information on mail-order prescriptions, volume, and payer type of
      retail prescriptions in rural vs urban areas. Together, these data provide a
      baseline for evaluating how implementation of the MMA may affect the financial
      viability of rural independent pharmacies. METHODS: Projections of prescriptions
      dispensed from retail and mail-order pharmacies in 2002 for the total US and a
      sample of 17 states were obtained from IMS Health. FINDINGS: The volume of mail
      order prescriptions is small. Rural providers prescribed fewer retail and mail
      order prescriptions per person, but more units per person. Rural areas have a
      higher percentage of prescriptions paid for by cash (18% vs 13%) and Medicaid
      (16% vs 10%) and a lower percentage of third-party payers than urban areas.
      Significant variation in volume and payer type exists between states.
      CONCLUSIONS: Rural, independent pharmacies may be negatively affected by MMA
      implementation as business shifts from cash to third-party reimbursement. The
      high degree of variation between states also has potentially important
      implications for the implementation of Prescription Drug Plan regions under MMA.

PMID- 15859049
TI  - Rural implications of Medicare's post-acute-care transfer payment policy.
AB  - CONTEXT: Under the Medicare post-acute-care (PAC) transfer policy, acute-care
      hospitals are reimbursed under a per-diem formula whenever beneficiaries are
      discharged from selected diagnosis-related groups (DRGs) to a skilled nursing
      facility, home health care, or a prospective payment system (PPS)-excluded
      facility. Total per-diem payments are below the full DRG payment only when the
      patient's length of stay (LOS) is short relative to the geometric mean LOS for
      the DRG; otherwise, the full DRG payment is received. This policy originally
      applied to 10 DRGs beginning in fiscal year 1999 and was expanded to additional
      DRGs in FY2004. The Secretary may include other DRGs and types of PAC settings in
      future expansions. PURPOSE: This article examines how the initial policy change
      affected rural and urban hospitals and investigates the likely impact of the
      FY2004 expansion and other possible future expansions. METHODS: The authors used
      1998-2001 Medicare Provider Analysis and Review (MEDPAR) data to investigate
      changes in hospital discharge patterns after the original policy was implemented,
      compute the change in Medicare revenue resulting from the payment change, and
      simulate the expected revenue reductions under expansions to additional DRGs and
      swing-bed discharges. FINDINGS: Neither rural nor urban hospitals appear to have
      made a sustained change in their discharge behavior so as to limit their exposure
      to the transfer policy. Financial impacts from the initial policy were similar in
      relative terms for both types of hospitals and would be expected to be fairly
      similar for an expansion to additional DRGs. On average, including swing-bed
      discharges in the transfer policy would have a very small financial impact on
      small rural hospitals; only hospitals that make extensive use of swing beds after
      a short inpatient stay might expect large declines in total Medicare revenue.
      CONCLUSION: Rural hospitals are not disproportionately harmed by the PAC transfer
      policy. An expanded policy may even benefit rural hospitals by recognizing their
      lower use of post-acute-care and readjusting DRG weights so that they are paid
      more appropriately when providing the full course of inpatient care.

PMID- 15859050
TI  - Assisted living in rural America: results from a national survey.
AB  - CONTEXT: Expanding the availability of long-term care (LTC) services and making
      them more responsive to consumer preferences is an important goal, particularly
      for elderly people living in rural areas who tend to be older and have greater
      functional limitations but less access to the range of LTC options available in
      metropolitan areas. One option that has been growing in popularity is assisted
      living facilities (ALFs). PURPOSE AND METHODS: This paper describes rural ALFs
      and compares them with metropolitan ALFs. Data were collected using a multistage
      sample design that yielded a nationally representative sample of ALFs. Telephone
      interviews were completed with administrators of 1,251 ALFs in 1998. FINDINGS:
      Nationwide, assisted living was largely administered by private payment, and
      there was an undersupply in rural areas. Compared with metropolitan ALFs, rural
      ALFs were smaller and less likely to offer the types of services and
      accommodations associated with the philosophy of assisted living. They were more
      likely to offer accommodations with little privacy, and while similar in the
      services they offered, rural ALFs were less likely to have nurses on staff,
      particularly licensed practical nurses. Moreover, they were less likely to offer
      a combination of high services and high privacy. Finally, rural ALFs charged
      lower prices than urban ALFs; however, the average price was still unaffordable
      for most elderly rural residents. CONCLUSIONS: These findings suggest that
      assisted living, as currently structured, will make only a marginal contribution
      to meeting the needs of frail elders in rural areas.

PMID- 15859051
TI  - A national study of obesity prevalence and trends by type of rural county.
AB  - CONTEXT: Obesity is epidemic in the United States, but information on this trend
      by type of rural locale is limited. PURPOSE: To estimate the prevalence of and
      recent trends in obesity among US adults residing in rural locations. METHODS:
      Analysis of data from the Behavioral Risk Factor Surveillance System (BRFSS) for
      the years 1994-1996 (n = 342,055) and 2000-2001 (n = 385,384). The main outcome
      measure was obesity (body mass index [BMI] > or = 30), as determined by
      calculating BMI from respondents' self-reported height and weight. RESULTS: In
      2000-2001, the prevalence of obesity was 23.0% (95% confidence interval [CI]
      22.6%-23.4%) for rural adults and 20.5% (95% CI 20.2%-20.7%) for their urban
      counterparts, representing increases of 4.8% (95% CI 4.2%-5.3%) and 5.5% (95% CI
      5.1%-5.9%), respectively, since 1994-1996. The highest obesity prevalence
      occurred in rural counties in Louisiana, Mississippi, and Texas; obesity
      prevalence increased for rural residents in all states but Florida over the study
      period. African Americans had the highest obesity prevalence of any group, up to
      31.4% (95% CI 29.1%-33.6) in rural counties adjacent to urban counties. The
      largest difference in obesity prevalence between those with a college education
      compared with those without a high school diploma occurred in urban areas (18.4%
      [95% CI 17.9%-18.9%] vs 23.5% [95% CI 22.5%-24.5%], respectively); the smallest
      difference occurred in small, remote rural counties (20.3% [95% CI 18.7%-21.9%]
      versus 22.3% [95% CI 20.7%-24.0%], respectively). CONCLUSIONS: The prevalence of
      obesity is higher in rural counties than in urban counties; obesity affects some
      residents of rural counties disproportionately.

PMID- 15859052
TI  - Geographic disparities in cervical cancer mortality: what are the roles of risk
      factor prevalence, screening, and use of recommended treatment?
AB  - CONTEXT: Despite advances in early detection and prevention of cervical cancer,
      women living in rural areas, and particularly in Appalachia, the rural South, the
      Texas/Mexico border, and the central valley of California, have had consistently
      higher rates of cervical cancer mortality than their counterparts in other areas
      during the past several decades. METHODS: This paper reviews the published
      literature from 1966 to July 2002 to assess three potential pathways underlying
      this excess mortality--high human papilloma virus (HPV) prevalence, lack of or
      infrequent screening and advanced disease at diagnosis, and under-use of
      recommended treatment and shorter survival. FINDINGS: Living in rural areas may
      impose barriers to cervical cancer control, including lack of transportation and
      medical care infrastructures. Population characteristics that place women at
      greater risk for developing and dying from cervical cancer, such as low income,
      lack of health insurance, and physician availability, are concentrated in rural
      areas. Published data, however, are insufficient to identify the key reasons for
      the observed mortality patterns. CONCLUSIONS: At this time, given the lack of
      definitive evidence in the published literature, decisions about priorities in
      areas with high rates of cervical cancer mortality will depend on knowledge of
      current levels of screening, incidence, and stage distribution; and service
      delivery infrastructures, resources, and acceptability of interventions to the
      target population.

PMID- 15859053
TI  - Delivery complications associated with prenatal care access for Medicaid-insured
      mothers in rural and urban hospitals.
AB  - CONTEXT: Pregnancy complications affect many women. It is likely that some
      complications can be avoided through routine primary and prenatal care of
      reasonable quality. PURPOSE: The authors examined access to health care during
      pregnancy for mothers insured by Medicaid. The access indicator is potentially
      avoidable maternity complications (PAMCs). Potentially avoidable maternity
      complications are often preventable through routine prenatal care, such as
      infection screening and treatment. The authors examined the risks of potentially
      avoidable maternity complications among rural and urban hospital deliveries for
      groups of mothers defined by race or ethnicity. METHODS: Data are from the year
      2000 Nationwide Inpatient Sample (NIS). The stratified sample represents all
      discharges from 20.5% of community hospitals in the United States. The Nationwide
      Inpatient Sample identifies hospital locations, but not patients' areas of
      residence. Analyses, which accounted for the sample design, included calculation
      of potentially avoidable maternity complication rates by race or ethnicity, chi2,
      t tests, and multivariate logistic regression. FINDINGS: Within groups defined by
      race or ethnicity, unadjusted rates for potentially avoidable maternity
      complications did not differ significantly by hospital location. Holding other
      factors constant, potentially avoidable maternity complications were less common
      in rural hospitals than in urban hospitals (odds ratio, 0.78; CI, 0.62 to 0.99).
      In rural hospitals, African Americans had notably higher risk for potentially
      avoidable maternity complications than did non-Hispanic whites (odds ratio, 1.72;
      CI, 1.26 to 2.36). In urban hospitals, risk of potentially avoidable maternity
      complications was not significantly higher for African Americans. Hispanics and
      Asians had notably lower risks of potentially avoidable maternity complications
      in urban hospitals than did non-Hispanic whites. CONCLUSIONS: Providers and
      policymakers should work to reduce the risks of potentially avoidable maternity
      complications for African American women in rural areas who are insured by
      Medicaid.

PMID- 15859054
TI  - Veterans Health Administration and Medicare outpatient health care utilization by
      older rural and urban New England veterans.
AB  - CONTEXT: Older veterans often use both the Veterans Health Administration (VHA)
      and Medicare to obtain health care services. PURPOSE: The authors sought to
      compare outpatient medical service utilization of Medicare-enrolled rural
      veterans with their urban counterparts in New England. METHODS: The authors
      combined VHA and Medicare databases and identified veterans who were age 65 and
      older and enrolled in Medicare fee-for-service plans, and they obtained records
      of all their VHA services in New England between 1997 and 1999. The authors used
      ZIP codes to designate rural or urban residence and categorized outpatient
      utilization into primary care, individual mental health care, non-mental health
      specialty care, or emergency room care. FINDINGS: Compared with their urban
      counterparts, veterans living in rural settings used significantly fewer VHA and
      Medicare-funded primary care, specialist care, and mental health care visits in
      all 3 years examined (P<.001 for all). Compared with urban veterans, veterans
      living in rural settings used fewer VHA emergency department services in 1998 and
      1999 but more Medicare-funded emergency department visits in 1997. The authors
      found some evidence of substitution of Medicare for VHA emergency visits in rural
      veterans, but no other evidence of like-service substitution. Rural veterans were
      more reliant on Medicare for primary care and on VHA services for specialty and
      mental health care. CONCLUSIONS: These findings suggest that rural access to
      federally funded health care is restricted relative to urban access. Older
      veterans may choose different systems of care for different health care services.
      With poor access to primary care, rural veterans may substitute emergency room
      visits for routine care.

PMID- 15859055
TI  - Improvements in care and reduced self-management barriers among rural patients
      with diabetes.
AB  - CONTEXT: Improved preventive care and clinical outcomes among patients with
      diabetes can reduce complications and costs; however, diabetes care continues to
      be suboptimal. Few studies have described effective strategies for improving care
      among rural populations with diabetes. PURPOSE: In 2000, the Park County Diabetes
      Project and the Montana Diabetes Control Program collaboratively implemented a
      countywide effort, which included health systems interventions and coordinated
      diabetes education, to improve the quality of diabetes care. METHODS: Clinical
      data from the diabetes registries in 2 primary care practices, in addition to
      baseline and follow-up telephone surveys, were used to evaluate improvements in
      care, outcomes, education, and barriers to self-management. FINDINGS: In the
      cohort of patients, the proportion receiving the following services increased
      significantly from 2000 to 2003: annual foot examination (43% to 58%), influenza
      (30% to 53%), and pneumoccocal immunizations (39% to 70%). The median hemoglobin
      A1c values decreased significantly from baseline to follow-up (7.2% to 6.8%).
      Mean systolic and diastolic blood pressure decreased significantly over the 2
      time periods (139 mmHg to 135 mmHg, and 78 mmHg to 75 mmHg, respectively).
      Significant decreases were also observed in barriers to self-management,
      including lack of knowledge (decrease from 12% to 5%), difficulties making
      lifestyle changes (36% to 27%), cost of monitors and test strips (25% to 16%),
      cost of medications (37% to 24%), and diabetes education (22% to 4%).
      CONCLUSIONS: Findings suggest that system changes in primary care practices and
      the implementation of accessible diabetes education can improve care and reduce
      barriers for rural patients with diabetes.

PMID- 15859056
TI  - Perceived barriers to nurse practitioner practice in rural settings.
AB  - CONTEXT: Rural residents experience the same incidence of acute illness as urban
      populations and have higher levels of chronic illness. Overall, access to
      adequate rural health care is limited. Nurse practitioners (NPs) have been
      identified as safe, cost-effective providers in meeting these challenges in rural
      settings. PURPOSE: This replication study was conducted to examine NP perceptions
      of barriers to rural practice in Minnesota. Findings were compared to earlier
      studies to examine issues that have persisted over time. METHODS: A Barriers to
      Practice checklist was mailed to NPs from the database of the Board of Nursing of
      a midwestern state. Rural NPs (n = 191) identified and described barriers to
      practice and rated the overall restrictiveness of their practice. FINDINGS:
      Barriers to practice were perceived to be prevalent. Persisting barriers
      continued to stand in the way of full utilization of NP roles. Lack of
      understanding of NP roles on the part of the public and other health
      professionals has been particularly problematic over time. Key issues in 2001
      were low salaries, lack of adequate office space, and a limited peer network.
      Perceived restrictiveness of the practice climate, gauged as somewhat
      restrictive, remained unchanged between 1996 and 2001. CONCLUSIONS: NPs have an
      excellent history of meeting rural primary health care needs. Enhancing the NP
      work environment could prove instrumental to retaining these professionals in the
      work force and thereby contribute to improved access and quality of care in
      underserved rural communities.

PMID- 15859057
TI  - Self-rated health among vulnerable older adults in rural Appalachia.
AB  - CONTEXT: Self-rated health (SRH) predicts service use, morbidity, and mortality.
      Additionally, SRH has been associated with indices of psychological well-being.
      PURPOSE: The main focus of the study was to investigate important differences
      among the lower spectrum of SRH (ie, fair and poor) on indices of well-being.
      METHODS: In-person interviews collected data from 207 (M age = 75.8) older rural
      adults. Data were used to examine differences between those reporting poor, fair,
      and good or excellent SRH on measures of demographics, and physical and
      psychological health. RESULTS: Significant differences emerged between levels of
      SRH in relation to measures of physical and psychological health. Specifically,
      individuals with poor SRH were significantly more likely to have (1) illnesses,
      (2) problems with basic and cognitive tasks of daily living, and (3) depressed
      affect than individuals reporting good or excellent health. Individuals with poor
      SRH were significantly more likely to have problems with basic and cognitive
      tasks of daily living than individuals with fair SRH. No significant differences
      were found between people reporting fair and good or excellent SRH on illnesses
      and depressed affect. CONCLUSIONS: Results suggest that future research should
      investigate the expansion of the lower-end of the SRH measure to more accurately
      assess SRH among vulnerable, rural older adults. Such efforts would better inform
      health care providers, practitioners, and policy makers in rural areas as to how
      SRH affects the well-being of vulnerable older adults.

PMID- 15859058
TI  - Herbal remedies used by selected migrant farmworkers in El Paso, Texas.
AB  - CONTEXT: Little is known about the use of complementary and alternative medicine
      among the approximately 1.6 million migrant farmworkers in the United States.
      PURPOSE: To evaluate the use of medicinal plants and natural remedies among a
      convenience sample of 100 migrant farmworkers living temporarily in a migrant
      worker center in El Paso, Texas. METHODS: A structured interview instrument was
      designed to elicit information about reasons for medicinal herb use, form in
      which herbs were ingested, serious side effects experienced, location of
      purchase, effectiveness of treatment, and use of allopathic medications.
      FINDINGS: The majority of workers used herbal remedies or other natural products
      because they believed them to be more effective than pharmaceuticals and because
      of tradition. Most learned about herbal remedies from a relative, primarily from
      their mother, and the majority who used herbal remedies believed them to be very
      helpful in treating specific illnesses. No adverse reactions to any herbal remedy
      were reported. The majority of participants did not inform their physician about
      their use of herbal remedies. According to the literature, potential adverse
      interactions between herbal remedies used and allopathic medications included
      gastrointestinal irritation, renal toxicity, and hypoglycemia. CONCLUSIONS:
      Health care providers must be knowledgeable about the use of herbal remedies
      among migrant farmworkers. By showing an understanding of and sensitivity to the
      use of these remedies, health care providers will be able to conduct more
      comprehensive health assessments of migrant workers and their families and
      provide them with more culturally competent care.

PMID- 15859059
TI  - Raman spectrometers and microscopes.

PMID- 15859060
TI  - The need for standardization of real-time PCR methods.

PMID- 15859061
TI  - Determination of metal concentration in fat supplements for swine nutrition by
      atomic absorption spectroscopy.
AB  - The presence of some essential and toxic metals in fat supplements for swine diet
      was investigated. Collected samples represented a relevant production of the
      Italian industry. In particular, some samples were enriched with antioxidants or
      waste cooking oils. The method for the determination of Ca, Cu, Cd, Fe, Mg, Mn,
      Ni, Pb, and Zn in fat samples was developed by means of a certified reference
      material (CRM 186) and a representative fatty sample (RFS). All samples were
      digested in closed vessels in a microwave oven and then analyzed by flame atomic
      absorption or graphite furnace atomic absorption spectrometry. The entire
      analytical method provided a satisfactory repeatability and reproducibility
      confirmed by agreement between the experimental recovery data obtained for the
      CRM 186 sample and, with the method of standard additions, for the RFS material.
      The samples generally showed a small amount of metals compared with the
      recommended daily intake for the essential elements. On the other hand, some
      samples contained a significant concentration, from an analytical point of view,
      of Cd, Ni, and Pb. Principal component analysis (PCA) was applied to inspect the
      experimental data obtained from samples analysis. Basically no differences were
      detected in terms of metal concentration among the fat supplements analyzed.

PMID- 15859062
TI  - Determination of pirimicarb and endosulfan in commercial pesticide formulations
      by Fourier transform infrared spectrometry.
AB  - A routine method based on Fourier transform infrared spectrometry was developed
      for the simultaneous determination of pirimicarb and endosulfan in commercially
      available pesticide formulations. The method is based on peak area absorbance
      measurements between 1362 and 1352 cm(-1), corrected with a baseline fixed at
      1338 cm(-1), for pirimicarb and peak area absorbance measurements between 919 and
      909 cm(-1) with a baseline fixed at 931 cm(-1) for endosulfan; chloroform
      solutions for analysis were obtained by direct dilution of emulsifiable
      concentrates or by solvent extraction from solid samples. Various extraction
      conditions and appropriate band selection were investigated, and interference
      studies were performed. Under the experimental conditions selected, limits of
      detection of 13 microg/g for pirimicarb and 150 microg/g for endosulfan were
      obtained that correspond to 0.13 and 1.6% (w/w), respectively, in commercial
      samples. Results from analyses of commercial samples by the developed method
      compared well with those obtained by a liquid chromatography reference method.

PMID- 15859063
TI  - Investigation of pyrrolizidine alkaloids and their N-oxides in commercial comfrey
      containing products and botanical materials by liquid chromatography electrospray
      ionization mass spectrometry.
AB  - Pyrrolizidine alkaloids (PAs) and their N-oxides are found in several plant
      families throughout the world. PAs are potentially toxic to the liver and/or
      lungs in humans and may cause acute liver failure, cirrhosis, pneumonitis, or
      pulmonary hypertension. PAs are also carcinogenic to animals, and they have been
      linked to the development of hepatocellular and skin squamous cell carcinomas as
      well as liver angiosarcomas. According to experimental studies, the quantity of
      PAs in some herbal teas and dietary supplements is sufficient to be carcinogenic
      in exposed individuals. A method for the extraction and identification of PAs and
      their N-oxides in botanical materials and commercial comfrey-containing products
      has been developed using liquid chromatography electrospray ionization mass
      spectrometry. Following optimization of the extraction procedure and the
      chromatographic conditions, the method was applied to the analysis of 10 herbal
      remedies. All of the products that were labeled to contain comfrey were found to
      contain measurable quantities of PAs.

PMID- 15859064
TI  - Precolumn derivatization liquid chromatography method for analysis of dietary
      supplements for glucosamine: single laboratory validation study.
AB  - A precolumn derivatization liquid chromatography (LC) method was developed for
      the analysis of various dietary supplement formulations and raw materials for
      glucosamine. A 1 mL sample or standard water solution (containing about 0.05 mg
      glucosamine) was mixed with 1 mL pH 8.3 buffer, 1 mL 5% phenylisothiocyanate
      methanolic solution, and derivatized at 80 degrees C in a water bath for 30 min.
      After derivatization, the solution was cooled in a cold water bath and
      centrifuged at 3000-5000 rpm. The clear upper layer was ready for injection. The
      LC system was equipped with a C18 reversed-phase column and an ultraviolet
      detector set at 240 nm. The column was developed with a linear gradient composed
      of 0.1% phosphoric acid in deionized water and 0.1% phosphoric acid in methanol.
      The method was subjected to Single Laboratory Validation. The method precision
      was 0.50% relative standard deviation, accuracy was less than +/-1.5%, method
      linearity in the range 0-2 mg glucosamine/mL was 1.00, the detection limit was
      0.0705 microg/mL, and the quantitation limit was 0.235 microg/mL. Chondroitin
      sulfate, amino acids, and excipients did not interfere with glucosamine testing.
      After derivatization, both standard and sample preparations were stable for at
      least 48 h. Due to its high sensitivity, this method can be used to assay
      glucosamine in functional foods and pet foods. The validation data will be
      published separately.

PMID- 15859065
TI  - Comparison of solid-phase microextraction, supercritical fluid extraction, steam
      distillation, and solvent extraction techniques for analysis of volatile
      consituents in Fructus Amomi.
AB  - Four sampling techniques, solid-phase microextraction (SPME), supercritical fluid
      extraction (SFE), steam distillation (SD), and solvent extraction (SE), were
      compared for the analysis of volatile constituents from a traditional Chinese
      medicine (TCM) of the dried ripe fruit of Fructus Amomi (Sha Ren). A total of 38
      compounds were identified by gas chromatography/mass spectrometry. Different SFE
      and SPME parameters (modifier content, extraction pressure, and temperature for
      SFE and fibers, extraction temperature, and time for SPME) were studied. The
      results by SFE and SPME were compared with those obtained by conventional SD and
      SE methods. The results showed that SFE and SPME are better sample preparation
      techniques than SD and SE. Due to SFE's requirement for expensive specialized
      instrumentation, the simplicity, low cost, and speed of SPME make it a more
      appropriate technique for extraction of volatile constituents in TCMs.

PMID- 15859066
TI  - Liquid chromatographic determination of cetirizine in oral formulations.
AB  - The development and validation of a reversed-phase liquid chromatographic (LC)
      method for the determination of cetirizine dihydrochloride in oral formulations
      are described. An isocratic LC analysis was performed on a reversed-phase C18
      column (250 x 4.6 mm id, 5 microm particle size). The mobile phase was 1%
      orthophosphoric acid solution, pH 3.0-acetonitrile (60 + 40, v/v), pumped at a
      constant flow rate of 1.0 mL/min. Measurements were made at a wavelength of 232
      nm. The calibration curves were linear over the range of 10-30 microg/mL (r2 =
      0.9999). The relative standard deviation (RSD) values for intraday precision were
      0.94 and 1.43% for tablets and compounded capsules, respectively. The RSD values
      for interday precision were 0.13 and 0.82% for tablets and compounded capsules,
      respectively. Recoveries ranged from 97.7 to 101.8% for tablets and from 98.4 to
      102% for compounded capsules. No interferences from the excipients were observed.
      Because of its simplicity and accuracy, the method is suitable for routine
      quality-control analysis for cetirizine in tablets and compounded capsules.

PMID- 15859067
TI  - Simultaneous determination of three opiates in serum by micellar liquid
      chromatography using direct injection.
AB  - A simple and reliable micellar liquid chromatographic method was developed for
      the simultaneous determination of 3 opiates (codeine, morphine, and thebaine) in
      serum, using direct injection and ultraviolet detection. The separation of the
      drugs was optimized on a C18 column, thermostatically controlled at 25 degrees C,
      by evaluating mobile phases containing sodium dodecyl sulfate (SDS) and various
      modifiers (propanol, butanol, or pentanol). Adequate resolution of the opiates
      was obtained with a chemometrics approach, in which retention was modeled as a
      first step by using the retention factors for several mobile phases. Next, an
      optimization criterion that takes into account the position and shape of the
      chromatographic peaks was applied. The 3 opiates were totally resolved and
      determined in 12 min with the mobile phase 0.15M SDS-7% (v/v) butanol buffered at
      pH 7. The limits of detection for codeine and morphine were greatly improved by
      using fluorimetric detection. Repeatability and intermediate precision were
      tested for 3 different concentrations of the drugs, and the relative standard
      deviations were <0.8% for most of the assays. Finally, the method was
      successfully applied to the determination of morphine and codeine in serum
      samples.

PMID- 15859068
TI  - Determination of ceftriaxone in cerebrospinal fluid by ion-pair liquid
      chromatography.
AB  - An ion-pair liquid chromatographic assay was developed and validated for the
      determination of ceftriaxone in cerebrospinal fluid. Chromatographic separation
      was achieved on a C18 column (125 x 4 mm, 5 microm) with detection at 270 nm, a 1
      mL/min flow rate and a 50 microL loop. The mobile phase consisted of 300 mL
      acetonitrile, 50 mL 0.1M phosphate buffer (pH 7.4), 3.2 g tetrabutylammonium
      bromide as the ion-pairing agent, and dilution with distilled deionized water to
      1 L. Cephradine was used as the internal standard. The assay was linear for
      ceftriaxone concentrations of 0.5-50 microg/mL. The coefficients of variation for
      precision were <4.61%. The accuracy ranged from 96.07 to 102.42%. The detection
      and quantitation limits were 0.019 and 0.065 microg/mL, respectively. This method
      was used to quantify ceftriaxone in the cerebrospinal fluid of children with
      meningitis. The results showed that the method described here is useful for the
      determination of ceftriaxone in cerebrospinal fluid.

PMID- 15859069
TI  - Calf antibiotic and sulfonamide test (CAST) for screening antibiotic and
      sulfonamide residues in calf carcasses.
AB  - The Calf Antibiotic and Sulfonamide Test (CAST), a microbial inhibition screening
      test, was developed for detecting antibiotics and sulfonamides in bob veal calf
      carcasses. The test uses Bacillus megaterium ATCC 9885 as the indicator organism
      and Mueller Hinton agar as the growth medium. Compared to Swab Test on Premises
      (STOP), developed in 1970, this screening test has higher sensitivity and the
      ability to detect a wider range of veterinary antimicrobial residual drugs,
      particularly sulfonamides, at lower concentrations. Carcasses that are tested
      with CAST and suspected of containing chemical residue above tolerance level are
      retained for confirmation. Disposition of these carcasses are determined upon
      laboratory result. Routine testing of bob veal calves with CAST allowed the Food
      Safety and Inspection Service to release most calf carcasses within 24 h post
      slaughter, thus conserving shipping and handling resources. However, changes in
      the regulation in 1990 dictate that disposition of carcasses found to contain
      violative levels of sulfonamide residues should be based on laboratory findings.
      The analysis of the data for the years 1990-1994 and 1998 indicate that the use
      of CAST over the years was significant, and had a direct impact on reduction of
      residue violations in veal carcasses. With the use of CAST, potentially harmful
      antimicrobial chemicals entering the human food chain through veal meat have been
      minimized.

PMID- 15859070
TI  - Fast antimicrobial screen test (FAST): improved screen test for detecting
      antimicrobial residues in meat tissue.
AB  - The Fast Antimicrobial Screen Test (FAST) is a simple and quick screening test
      developed to detect antibiotic and sulfonamide residues in food animal carcasses
      in slaughter establishments. This microbial inhibition test detects
      antimicrobials that are allowed to be used in food animals. It has the ability to
      detect these antimicrobials at or above the allowable limit in carcass kidney
      fluids in 6 h. Laboratory evaluations show that the lower limit of detection
      (LLD) of FAST and the Calf Antibiotic and Sulfa Test (CAST) for antibiotics
      tested was the same, but the LLD for sulfonamides of FAST was lower than the LLD
      of CAST. Compared with the Swab Test on Premises (STOP) developed in 1977, the
      LLD's of FAST for both antibiotics and sulfonamides were significantly better.
      Under field conditions, the sensitivity of FAST and CAST to antibiotic and
      sulfonamide residues in animal kidneys was not significantly different, but the
      time required by FAST was significantly lower than CAST (6 versus 18 h). Compared
      with the STOP, the sensitivity and the range of detection by FAST for all
      antimicrobials were significantly higher and the testing time was lower (18
      versus 6 h).

PMID- 15859071
TI  - Spectrofluorimetric determination of warfarin sodium by using N1
      methylnicotinamide chloride as a fluorigenic agent.
AB  - A spectrofluorimetric method is described for the determination of drugs
      containing active methylene groups adjacent to carbonyl groups. The method was
      applied successfully to the determination of warfarin sodium in laboratory
      prepared mixtures, in commercial tablets, and in spiked human plasma samples.
      Finally, the method was applied to the determination of the steady-state
      concentration of warfarin sodium in the blood of a hospitalized patient. The
      method involves the reaction of warfarin sodium with 0.2 ml (0.4 x 10(-3)M) N1
      methylnicotinamide chloride reagent in the presence of 3 mL 1.0N NaOH and cooling
      in ice for 8 min, followed by adjustment of the pH to 2.0, using formic acid and
      heating for 4 min, whereby a highly fluorescent reaction product is produced. The
      optimal wavelengths of excitation and emission were determined by using a
      synchronous wavelength search and found to be 284 and 354 nm, respectively. The
      standard curves were linear over a concentration range of 50-1500 ng/mL in both
      aqueous solutions and spiked human plasma samples. The mean recoveries (+/-
      standard deviation) were 101.157 (+/-1.33) and 95.73 (+/-1.88%) for aqueous
      solutions and spiked human plasma samples, respectively. The method showed good
      specificity and precision. The proposed method is simple and economical because
      of its minimal instrumentation and chemicals requirements. Nevertheless, it is
      highly sensitive, specific, and reproducible. Accordingly, it is suitable for
      quality-control applications, drug monitoring, and bioavailability and
      bioequivalency studies.

PMID- 15859072
TI  - Determination of emamectin benzoate in medicated fish feed: a multisite study.
AB  - A new method was developed for the quantitation of emamectin benzoate in
      medicated fish feed at levels between 1 and 30 ppm. The new procedure, based on a
      previously reported assay, consists of a wet methanolic extraction of ground
      feed, followed by solid-phase extraction and injection onto a gradient liquid
      chromatographic system. A multisite study involving 3 laboratories (the
      developing laboratory and 2 independent laboratories) was performed to evaluate
      precision, recovery, linearity, and sensitivity. Mean recove;ries for triplicate
      analyses at 3 levels, performed by 2 analysts per laboratory, were between 89 and
      97%, with coefficients of variation ranging from 1.6 to 8.6%. Coefficients of
      determination (r2) obtained from the plotted data were > or =0.993. The precision
      of the method, determined from 6 replicate preparations from the same batch of
      medicated feed assayed in 3 separate trials per laboratory, was between 0.6 and
      5.8%. The quantitation limit was established at 0.5 ppm. Specificity and
      robustness studies were performed by the developing laboratory.

PMID- 15859073
TI  - Comparison study of two procedures for the determination of emamectin benzoate in
      medicated fish feed.
AB  - A new method has been developed for the determination of emamectin benzoate in
      fish feed. The method uses a wet extraction, cleanup by solid-phase extraction,
      and quantitation and separation by liquid chromatography (LC). In this paper, we
      compare the performance of this method with that of a previously reported LC
      assay for the determination of emamectin benzoate in fish feed. Although similar
      to the previous method, the new procedure uses a different sample pretreatment,
      wet extraction, and quantitation method. The performance of the new method was
      compared with that of the previously reported method by analyses of 22 medicated
      feed samples from various commercial sources. A comparison of the results
      presented here reveals slightly lower assay values obtained with the new method.
      Although a paired sample t-test indicates the difference in results is
      significant, this difference is within the method precision of either procedure.

PMID- 15859074
TI  - Development of liquid chromatographic methods for determination of quinocetone
      and its main metabolites in edible tissues of swine and chicken.
AB  - Quinocetone (QCT), a new antimicrobial growth promotant of quinoxalines, can
      effectively improve the growth and feed efficiency of food animals with more
      safety than is provided by olaquindox and carbadox. To clarify its metabolism and
      residue levels in animals, a liquid chromatographic method with UV-Vis detection
      was developed for the determination of QCT and its main metabolites,
      desoxyquinocetone (DQCT) and 3-methylquinoxaline-2-carboxylic acid (MQCA), in
      muscle, liver, kidney, and fat of swine and chicken. For sample pretreatment, QCT
      and DQCT were extracted with ethyl acetate and purified with iso-octane; after
      alkaline hydrolysis of the tissue, MQCA was extracted with ethyl acetate and
      citric acid buffer (pH 6.0), and the extract was purified over a cation-exchange
      column (AG MP-50 resin). Detection was at 312 and 320 nm for QCT and DQCT,
      respectively, and at 320 nm for MQCA. The observed limit of detection for the 3
      compounds was 0.025 microg/g in various tissues. The methods were linear over the
      concentrations range of 0.01-0.64 microg/mL with mean recoveries of approximately
      71-86% and relative standard deviations of about 4-12% at the levels of 0.05,
      0.10, and 0.20 microg/g. The method is highly selective and can be applied to the
      determination of QCT and its main metabolites in animal tissues, which would
      accelerate the pharmacokinetic and residue study of QCT in food animals.

PMID- 15859075
TI  - Study of the liquid chromatography retention of some fibrate-type
      antihyperlipidemic drugs on C18 and CN columns: application for quantitation in
      pharmaceutical formulations.
AB  - The 6 antihyperlipidemic agents-bezafibrate, ciprofibrate, clofibrate, clofibric
      acid, fenofibrate, and gemfibrozil-were separated on octadecyl (C18) and cyano
      (CN) chemically bonded columns using mobile phases containing phosphate buffer
      and different amounts of acetonitrile, dioxane, propan-2-ol, methanol, and
      tetrahydrofuran. Relationships between log k values and mobile phase composition
      have been examined for these systems. Analysis was performed on a Waters LC
      system with Merck LichroCART C18 and CN 125 mm columns using a flow rate of 1
      mL/min and 227 nm detection. More than one-half of the results fitted Snyder
      Soczewinski equations with r >0.995. Separation of all drugs was achieved on the
      C18 column with a mobile phase containing 45% propan-2-ol in phosphate buffer (pH
      = 2.145) and on a CN column with 20% acetonitrile in the same buffer. The best
      mobile phase, containing 45% propan-2-ol, was used to quantitate bezafibrate,
      ciprofibrate, fenofibrate, and gemfibrozil in pharmaceutical formulations. The
      active substances were extracted with methanol. The calibration curve was
      constructed in the 0.1-0.8 mg/mL range for all drugs and provided satisfactory
      linearity (Lack-of-Fit test and Mandel's test). The recovery function was
      sufficiently linear in all cases, with an insignificant intercept and slope very
      close to 1. Accuracy was tested by quantitating 3 fortified samples (50, 100, and
      150%), which gave results without significant differences. None of the excipients
      interfered in the analysis. The recovery was 99.85% for bezafibrate, 99.02% for
      ciprofibrate, 99.53% for fenofibrate, and 99.92% for gemfibrozil, with relative
      standard deviation values of 0.63, 1.61, 1.84, and 0.88%, respectively.

PMID- 15859076
TI  - Spectrophotometric methods for the determination of the antidepressant drug
      paroxetine hydrochloride in tablets.
AB  - Simple, sensitive, and accurate visible spectrophotometric methods are described
      for the determination of paroxetine hydrochloride (PA) in tablets. Among them,
      the first 3 methods are based on the ion-pair complexes of PA formed with
      bromothymol blue (BTB), bromophenol blue (BPB), and bromocresol green (BCG) in
      aqueous acidic buffers. The complex species extracted into chloroform were
      quantitatively measured at 414 nm with BTB and BCG and at 412 nm with BPB. Beer's
      law was obeyed over the concentration ranges of 2-20, 2-16, and 2-16 microg/mL,
      respectively. The fourth method described is based on a coupling reaction between
      PA and 7-chloro-4-nitrobenzofurazon (NBD-Cl) in borate buffer, pH 8.5, in which a
      yellow reaction product that was measured at 478 nm was formed. The Beer's law
      range for this method was 2-10 microg/mL. The last method developed describes the
      interaction of PA base, as an n-electron donor, with 7,7,8,8
      tetracyanoquinodimethane (TCNQ), as a pi-acceptor, in acetonitrile to give blue
      colored TCNQ- radical anion with absorption maxima at 750 and 845 nm. Measured at
      845 nm, the absorbance-concentration plot was rectilinear over the range of 1.5
      15 microg/mL. The new methods developed were successfully applied to the
      determination of PA in tablets without any interference from common tablet
      excipients. The results of the methods were in good agreement with those obtained
      with an official liquid chromatographic method. This report describes first
      colorimetric methods for the determination of PA.

PMID- 15859077
TI  - Simultaneous determination of residues of dipyrone and its major metabolites in
      milk, bovine muscle, and porcine muscle by liquid chromatography/mass
      spectrometry.
AB  - A new liquid chromatography/mass spectrometry (LC/MS) method for the
      determination of dipyrone (DIP) and the DIP-related residues 4
      formylaminoantipyrine (FAA), 4-aminoantipyrine (AA), and 4-methylaminoantipyrine
      (MAA) in milk, bovine muscle, and porcine muscle is presented. The analytes are
      extracted from the sample with methanol and defatted with hexane. The methanol
      extracts are then concentrated and injected into the LC system. Compounds are
      determined by reversed-phase LC using an Inertsil ODS-3 column with ammonium
      formate-acetonitrile mobile phase and MS detection using positive-ion
      electrospray ionization. Calibration curves were linear between 0.02 and 0.20
      microg/g matrix equivalent concentration for FAA, AA, and MAA, and between 0.2
      and 2.0 microg/g for DIP. The relative standard deviations for measurements by
      the proposed method were <11% for milk and porcine samples, with slightly greater
      variability for bovine samples. Average recoveries ranged from 82 to 128%,
      depending on the compound and matrix involved. The method detection limits of
      FAA, AA, and MAA were <0.02 microg/g for all matrixes tested, while those of DIP
      were <0.13 microg/g. The proposed method is rapid, simple, and specific, allowing
      a single analyst to easily prepare over 20 samples in a regular working day.

PMID- 15859078
TI  - Determination of oxytetracycline in salmon by liquid chromatography with metal
      chelate fluorescence detection.
AB  - A liquid chromatography (LC) method is described for the determination of
      oxytetracycline (OTC) in farmed Atlantic salmon muscle tissue. The method
      involves homogenization of salmon tissue, extraction of OTC into Mcllvaine-EDTA
      buffer, acid precipitation of proteins, cleanup through tandem solid-phase
      extraction cartridges (Strata-X and aminopropyl), elution with mobile phase
      containing slightly alkaline buffer and Mg2+, and LC separation with metal
      chelate induced fluorescence detection. Salmon tissue was fortified with 0.10,
      0.25, 0.50, 0.75, and 1.0 microg/g (ppm) oxytetracycline. Average absolute
      recoveries were 84, 76, 70, 76, and 85%, respectively, with relative standard
      deviation (RSD) values all less than 9%. The interassay average recovery was 78%,
      with a 4.2% RSD. Determination was based on a standard graph using peak areas
      with standard solutions equivalent to 0.0625, 0.125, 0.25, 0.50, and 1.0 ppm in
      tissue. A set of 5 matrix controls (unfortified salmon tissue) were also
      analyzed, in which no OTC was detected. The lowest standard was used as the limit
      of quantitation.

PMID- 15859079
TI  - Evaluation of a chromogenic medium for identification and differentiation of
      Listeria monocytogenes in selected foods.
AB  - Listeria monocytogenes continues to be a threat to food safety in the United
      States despite a "zero tolerance" policy. When Listeria species are identified by
      standard cultural methods, confirmation of L. monocytogenes takes days to
      complete. RAPID'L.Mono agar, developed by Bio-Rad Laboratories, is a chromogenic
      medium that differentiates L. monocytogenes from other species of Listeria by a
      simple color change reaction. Differentiation is based on the specific detection
      of phosphatidylinositol phospholipase C activity, resulting in a blue colony, and
      the inability of L. monocytogenes to metabolize xylose, resulting in the absence
      of a yellow halo. Detection principles of standard method agars, Oxford and
      PALCAM, are based on the ability of all species of Listeria to hydrolyze esculin.
      Thus, all species of Listeria have similar colony morphology on these agars,
      making differentiation of pathogenic L. monocytogenes from other nonhuman
      pathogens difficult. RAPID'L.Mono agar has been validated with surimi, mixed
      salad, brie, and processed deli turkey because of the prevalence of L.
      monocytogenes in these foods. Sensitivity and specificity for this medium was
      determined to be 99.4 and 100%, respectively. Overall method agreement of
      RAPID'L.Mono with standard culture methods (U.S. Department of Agriculture/Food
      Safety and Inspection Service; U.S. Food and Drug Administration/Bacteriological
      Analytical Manual; and AOAC INTERNATIONAL) was excellent, with enrichment
      protocols 24 h shorter than those of standard methods.

PMID- 15859080
TI  - Liquid chromatographic method for quantitation of patulin at 10 ng/mL in apple
      based products intended for infants: interlaboratory study.
AB  - An interlaboratory trial for the determination of patulin in apple juice and
      fruit puree was conducted, involving 17 participants representing a cross section
      of industry, official food control, and research facilities. Mean recoveries
      reported ranged from 74 (10 ng/g) to 62% (25 ng/g) for apple juice and from 72
      (25 ng/g) to 74% (10 ng/g) for fruit puree. Based on results for spiked samples
      (blind pairs at 2 levels), as well as naturally contaminated samples (blind pairs
      at 3 levels), the relative standard deviation for repeatability (RSDr) in juice
      ranged from 8.0 to 14.3% and in puree from 3.5 to 9.3%. The relative standard
      deviation for reproducibility (RSD(R)) in juice ranged from 19.8 to 39.5% and in
      puree from 12.5 to 35.2%, reflecting HORRAT values from 0.6 to 1.0 for juice and
      0.4 to 0.9 for puree. The method showed acceptable within-laboratory and between
      laboratory precision for each matrix, as required by current European
      legislation.

PMID- 15859081
TI  - Immunoaffinity column cleanup with liquid chromatography using post-column
      bromination for determination of aflatoxins in hazelnut paste: interlaboratory
      study.
AB  - An interlaboratory study was conducted to evaluate the effectiveness of an
      immunoaffinity column cleanup liquid chromatography (LC) method for determination
      of aflatoxin B1 and total aflatoxins in hazelnut paste at European regulatory
      limits. The test portion was extracted with methanol-water (6 + 4). The extract
      was filtered, diluted with phosphate-buffered saline (PBS) solution to a
      specified solvent concentration, and applied to an immunoaffinity column
      containing antibodies specific to aflatoxins. The aflatoxins were removed from
      the immunoaffinity column with methanol, and then quantified by reversed-phase LC
      with post-column derivatization (PCD) involving bromination. The PCD was achieved
      with electrochemically generated bromine (Kobra Cell) followed by fluorescence
      detection (except for one participant who used pyridinum hydrobromide perbromide
      for bromination). Hazelnut paste, both naturally contaminated with aflatoxins and
      blank (<0.1 ng/g) for spiking by participants with aflatoxins, was sent to 14
      collaborators in Belgium, The Netherlands, Spain, Turkey, the United Kingdom, and
      the United States. Test portions were spiked at levels of 4.0 and 10.0 ng/g for
      total aflatoxins by participants using supplied total aflatoxins standards.
      Recoveries for total aflatoxins and aflatoxin B1 averaged from 86 to 89%. Based
      on results for naturally contaminated samples (blind duplicates at 3 levels
      ranging from 4.0 to 11.8 ng/g total aflatoxins), the relative standard deviation
      for repeatability (RSDr) ranged from 2.3 to 3.4% for total aflatoxins and from
      2.2 to 3.2% for aflatoxin B1. The relative standard deviation for reproducibility
      (RSD(R)) ranged from 6.1 to 7.0% for total aflatoxins and from 7.3 to 7.8% for
      aflatoxin B1. The method showed exceptionally good within-laboratory and between
      laboratory precision for hazelnut paste, as evidenced by HORRAT values, which in
      all cases were significantly below target levels, the low levels of determination
      for both aflatoxin B1 and total aflatoxins.

PMID- 15859082
TI  - Characterization and event specific-detection by quantitative real-time PCR of
      T25 maize insert.
AB  - T25 is one of the 4 maize transformation events from which commercial lines have
      so far been authorized in Europe. It was created by polyethylene glycol-mediated
      transformation using a construct bearing one copy of the synthetic pat gene
      associated with both promoter and terminator of the 35S ribosomal gene from
      cauliflower mosaic virus. In this article, we report the sequencing of the whole
      T25 insert and the characterization of its integration site by using a genome
      walking strategy. Our results confirmed that one intact copy of the initial
      construct had been integrated in the plant genome. They also revealed, at the 5'
      junction of the insert, the presence of a second truncated 35S promoter, probably
      resulting from rearrangements which may have occurred before or during
      integration of the plasmid DNA. The analysis of the junction fragments showed
      that the integration site of the insert presented high homologies with the Huck
      retrotransposon family. By using one primer annealing in the maize genome and the
      other in the 5' end of the integrated DNA, we developed a reliable event-specific
      detection system for T25 maize. To provide means to comply with the European
      regulation, a real-time PCR test was designed for specific quantitation of T25
      event by using Taqman chemistry.

PMID- 15859083
TI  - Quantification of the 35S promoter in DNA extracts from genetically modified
      organisms using real-time polymerase chain reaction and specificity assessment on
      various genetically modified organisms, part I: operating procedure.
AB  - A highly sensitive quantitative real-time assay targeted on the 35S promoter of a
      commercial genetically modified organism (GMO) was characterized (sF/sR primers)
      and developed for an ABI Prism 7700 Sequence Detection System and TaqMan
      chemistry. The specificity assessment and performance criteria of sF/sR assay
      were compared to other P35S-targeted published assays. sF/sR primers amplified a
      79 base pair DNA sequence located in a part of P35S that is highly conserved
      among many caulimovirus strains, i.e., this consensus part of CaMV P35S is likely
      to be present in many GM events. According to the experimental conditions, the
      absolute limit of detection for Bt176 corn was estimated between 0.2 and 2 copies
      of equivalent genome (CEG). The limit of quantification was reached below 0.1%
      Bt176 content. A Cauliflower Mosaic Virus control (CaMV) qualitative assay
      targeted on the ORF III of the viral genome was also used as a control (primers
      3F/3R) to assess the presence of CaMV in plant-derived products. The specificity
      of this test was assessed on various CaMV strains, including the Figwort Mosaic
      Virus (FMV) and solanaceous CaMV strains. Considering the performance of sF/sR
      quantification test, the highly conserved sequence, and the small size of the
      amplicon, this assay was tested in a collaborative study in order to be proposed
      as an international standard.

PMID- 15859084
TI  - Quantitation of 35S promoter in maize DNA extracts from genetically modified
      organisms using real-time polymerase chain reaction, part 2: interlaboratory
      study.
AB  - The European Committee for Standardization (CEN) and the European Network of GMO
      Working Laboratories have proposed development of a modular strategy for stepwise
      validation of complex analytical techniques. When applied to the quantitation of
      genetically modified organisms (GMOs) in food products, the instrumental
      quantitation step of the technique is separately validated from the DNA
      extraction step to better control the sources of uncertainty and facilitate the
      validation of GMO-specific polymerase chain reaction (PCR) tests. This paper
      presents the results of an interlaboratory study on the quantitation step of the
      method standardized by CEN for the detection of a regulatory element commonly
      inserted in GMO maize-based foods. This is focused on the quantitation of P35S
      promoter through using the quantitative real-time PCR (QRT-PCR). Fifteen French
      laboratories participated in the interlaboratory study of the P35S quantitation
      operating procedure on DNA extract samples using either the thermal cycler ABI
      Prism 7700 (Applied Biosystems, Foster City, CA) or Light Cycler (Roche
      Diagnostics, Indianapolis, IN). Attention was focused on DNA extract samples used
      to calibrate the method and unknown extract samples. Data were processed
      according to the recommendations of ISO 5725 standard. Performance criteria,
      obtained using the robust algorithm, were compared to the classic data processing
      after rejection of outliers by the Cochran and Grubbs tests. Two laboratories
      were detected as outliers by the Grubbs test. The robust precision criteria gave
      values between the classical values estimated before and after rejection of the
      outliers. Using the robust method, the relative expanded uncertainty by the
      quantitation method is about 20% for a 1% Bt176 content, whereas it can reach 40%
      for a 0.1% Bt176. The performances of the quantitation assay are relevant to the
      application of the European regulation, which has an accepted tolerance interval
      of about +/-50%. These data were fitted to a power model (r2 = 0.96). Thanks to
      this model, it is possible to propose an estimation of uncertainty of the QRT-PCR
      quantitation step and an uncertainty budget depending on the analytical
      conditions.

PMID- 15859085
TI  - Determination of furan levels in coffee using automated solid-phase
      microextraction and gas chromatography/mass spectrometry.
AB  - Furan is a 5-member ring chemical with high volatility. Because it is highly
      volatile, furan levels in foods are not easily determined with accuracy. In this
      study, an analytical method for furan analysis using an automated solid-phase
      microextraction system in combination with gas chromatography/mass spectroscopy
      is described. The performance of the method was demonstrated by the results
      obtained from a variety of coffees. Furan was detected at part-per-billion levels
      in coffee. The limit of detection was 0.3 ng/g and limit of quantitation, 0.8
      ng/g. The percent recoveries were between 92 and 102.

PMID- 15859086
TI  - Novel reference gene, High-mobility-group protein I/Y, used in qualitative and
      real-time quantitative polymerase chain reaction detection of transgenic rapeseed
      cultivars.
AB  - With the development of transgenic crops, regulations to label the genetically
      modified organisms (GMOs) and their derived products have been issued in many
      countries. Polymerase chain reaction (PCR) methods are thought to be reliable and
      useful techniques for qualitative and quantitative detection of GMOs. These
      methods are generally needed to amplify the transgene and compare the amplified
      results with that of a corresponding reference gene to get the reliable results.
      Specific primers were developed for the rapeseed (Brassica napus), high-mobility
      group protein I/Y(HMG-I/Y) single-copy gene and PCR cycling conditions suitable
      for the use of this sequence as an endogenous reference gene in both qualitative
      and quantitative PCR assays. Both methods were assayed with 15 different rapeseed
      varieties, and identical amplified products were obtained with all of them. No
      amplification was observed when templates were the DNA samples from the other
      species of Brassica genus or other species, such as broccoli, stem mustard,
      cauliflower, Chinese cabbage, cabbage, sprouts, Arabidopsis thaliana, carrot,
      tobacco, soybean, mung bean, tomato, pepper, eggplant, plum, wheat, maize,
      barley, rice, lupine, and sunflower. This system was specific for rapeseed.
      Limits of detection and quantitation in qualitative and quantitative PCR systems
      were about 13 pg DNA (about 10 haploid genomes) and about 1.3 pg DNA (about 1
      haploid genome), respectively. To further test the feasibility of this HMG-I/Y
      gene as an endogenous reference gene, samples containing transgenic rapeseed GT73
      with the inserted glyphosate oxidoreductase (GOX) gene were quantitated. These
      demonstrated that the endogenous PCR detection systems were applicable to the
      qualitative and quantitative detection of transgenic rapeseed.

PMID- 15859087
TI  - Focused ultrasound versus microwave digestion for the determination of lead in
      must by electrothermal-atomic absorption spectrometry.
AB  - The content of metals at the different stages of the winemaking process is of
      great concern because of legal and wine quality reasons. In the present work, we
      have developed a new fast procedure for metal extraction from must based on
      focused ultrasound with HNO3 and H2O2, with which microwave digestion of the must
      is not necessary. Lead was used as a model element to achieve the optimum
      combination of reagents in order to achieve total extraction. Results were
      compared with those obtained after microwave digestion of the samples. In
      addition, conventional and fast programs in conjunction with different matrix
      modifiers were studied. The method requires few sample mass (ca 0.5 g) and few
      reagents in low volume (HNO3 50 microL and H2O2 100 microL). The total sample
      treatment time is only 60 s.

PMID- 15859088
TI  - Determination of diethanolamine in shampoo products containing fatty acid
      diethanolamides by liquid chromatography with a thermal energy analyzer.
AB  - A liquid chromatography (LC) method using a thermal energy analyzer (TEA) is
      described for the determination of diethanolamine (DEA) in shampoo products
      containing fatty acid diethanolamides. DEA was converted to N
      nitrosodiethanolamine (NDELA) by dissolving a portion of the product in 6M acetic
      acid and mixing with sodium nitrite for 1 h at room temperature. The reaction
      mixture was dried, dissolved in acetone, and analyzed for NDELA by LC-TEA. The
      recovery of DEA from 2 shampoo products at fortification levels of 25, 250, and
      1000 ppm ranged from 70 to 105%. Twenty shampoo products were analyzed by this
      method, and 19 were found to contain DEA at levels ranging from 140 to 15 200
      ppm.

PMID- 15859089
TI  - Validation of a fast and easy method for the determination of residues from 229
      pesticides in fruits and vegetables using gas and liquid chromatography and mass
      spectrometric detection.
AB  - Validation experiments were conducted of a simple, fast, and inexpensive method
      for the determination of 229 pesticides fortified at 10-100 ng/g in lettuce and
      orange matrixes. The method is known as the quick, easy, cheap, effective,
      rugged, and safe (QuEChERS) method for pesticide residues in foods. The procedure
      involved the extraction of a 15 g sample with 15 mL acetonitrile, followed by a
      liquid-liquid partitioning step performed by adding 6 g anhydrous MgSO4 plus 1.5
      g NaCl. After centrifugation, the extract was decanted into a tube containing 300
      mg primary secondary amine (PSA) sorbent plus 1.8 g anhydrous MgSO4, which
      constituted a cleanup procedure called dispersive solid-phase extraction
      (dispersive SPE). After a second shaking and centrifugation step, the
      acetonitrile extract was transferred to autosampler vials for concurrent analysis
      by gas chromatography/mass spectrometry with an ion trap instrument and liquid
      chromatography/tandem mass spectrometry with a triple quadrupole instrument using
      electrospray ionization. Each analytical method was designed to analyze 144
      pesticides, with 59 targeted by both instruments. Recoveries for all but 11 of
      the analytes in at least one of the matrixes were between 70-120% (90-110% for
      206 pesticides), and repeatabilities typically <10% were achieved for a wide
      range of fortified pesticides, including methamidophos, spinosad, imidacloprid,
      and imazalil. Dispersive SPE with PSA retained carboxylic acids (e.g.,
      daminozide), and <50% recoveries were obtained for asulam, pyridate, dicofol,
      thiram, and chlorothalonil. Many actual samples and proficiency test samples were
      analyzed by the method, and the results compared favorably with those from
      traditional methods.

PMID- 15859090
TI  - Use of buffering and other means to improve results of problematic pesticides in
      a fast and easy method for residue analysis of fruits and vegetables.
AB  - A modification that entails the use of buffering during extraction was made to
      further improve results for certain problematic pesticides (e.g., folpet,
      dichlofluanid, chlorothalonil, and pymetrozine) in a simple, fast, and
      inexpensive method for the determination of pesticides in produce. The method,
      known as the quick, easy, cheap, effective, rugged, and safe (QuEChERS) method
      for pesticide residues in foods, now involves the extraction of the sample with
      acetonitrile (MeCN) containing 1% acetic acid (HAc) and simultaneous liquid
      liquid partitioning formed by adding anhydrous MgSO4 plus sodium acetate (NaAc).
      The extraction method is carried out by shaking a centrifuge tube which contains
      1 mL of 1% HAc in MeCN plus 0.4 g anhydrous MgSO4 and 0.1 g anhydrous NaAc per g
      sample. The tube is then centrifuged, and a portion of the extract is transferred
      to a tube containing 50 mg primary secondary amine sorbent plus 150 mg anhydrous
      MgSO4/mL of extract. After a mixing and centrifugation step, the extract is
      transferred to autosampler vials for concurrent analysis by gas
      chromatography/mass spectrometry (GC/MS) and liquid chromatography/tandem mass
      spectrometry. Independent of the original sample pH, the use of buffering during
      the extraction yields pH <4 in the MeCN extract and >5 in the water phase, which
      increases recoveries of both acid- and base-sensitive pesticides. The method was
      evaluated for 32 diverse pesticides in different matrixes, and typical percent
      recoveries were 95 +/- 10, even for some problematic pesticides. Optional solvent
      exchange to toluene prior to GC/MS analysis was also evaluated, showing equally
      good results with the benefit of lower detection limits, but at the cost of more
      time, material, labor, and expense.

PMID- 15859091
TI  - Evaluation of two fast and easy methods for pesticide residue analysis in fatty
      food matrixes.
AB  - Two rapid methods of sample preparation and analysis of fatty foods (e.g., milk,
      eggs, and avocado) were evaluated and compared for 32 pesticide residues
      representing a wide range of physicochemical properties. One method, dubbed the
      quick, easy, cheap, effective, rugged, and safe (QuEChERS) method for pesticide
      residue analysis, entailed extraction of 15 g sample with 15 mL acetonitrile
      (MeCN) containing 1% acetic acid followed by addition of 6 g anhydrous magnesium
      sulfate and 1.5 g sodium acetate. After centrifugation, 1 mL of the buffered MeCN
      extract underwent a cleanup step (in a technique known as dispersive solid-phase
      extraction) using 50 mg each of C18 and primary secondary amine sorbents plus 150
      mg MgSO4. The second method incorporated a form of matrix solid-phase dispersion
      (MSPD), in which 0.5 g sample plus 2 g C18 and 2 g anhydrous sodium sulfate was
      mixed in a mortar and pestle and added above a 2 g Florisil column on a vacuum
      manifold. Then, 5 x 2 mL MeCN was used to elute the pesticide analytes from the
      sample into a collection tube, and the extract was concentrated to 0.5 mL by
      evaporation. Extracts in both methods were analyzed concurrently by gas
      chromatography/mass spectrometry and liquid chromatography/tandem mass
      spectrometry. The recoveries of semi-polar and polar pesticides were typically
      100% in both methods (except that basic pesticides, such as thiabendazole and
      imazalil, were not recovered in the MSPD method), but recovery of nonpolar
      pesticides decreased as fat content of the sample increased. This trend was more
      pronounced in the QuEChERS method, in which case the most lipophilic analyte
      tested, hexachlorobenzene, gave 27 +/- 1% recovery (n=6) in avocado (15% fat)
      with a<10 ng/g limit of quantitation.

PMID- 15859092
TI  - A double-line sequential injection system for the spectrophotometric
      determination of copper, iron, manganese, and zinc in waters.
AB  - A double-line sequential injection system was developed for the
      spectrophotometric determination of several metal ions in waters. The proposed
      double-line configuration was used to enable adding sample and chromogenic
      reagents as merging zones. The methodology was applied to the spectrophotometric
      determination of copper, iron, manganese, and zinc in samples of diverse origins
      at the range of 0.15-5.00, 0.10-10.0, 0.48-4.00, and 0.11-5.00 mg/L,
      respectively. Different chromogenic reagents and detection wavelengths were used.
      The chromogenic reagents for iron and manganese were 1,10-phenanthroline and
      formaldoxime, respectively. Copper and zinc were both determined using the
      analytical reagent zincon. Analytical characteristics of the methodology, such as
      manifold parameters, buffer pH, and reagent concentrations were optimized, and
      interference of some of the metal ions commonly present in water sample was
      assessed. Results of the analysis were in agreement with those obtained by atomic
      absorption spectrometry. Repeatability, expressed as the relative standard
      deviation for 10 consecutive injections of water samples, was lower than 6%. The
      determination rate was approximately 36/h.

PMID- 15859093
TI  - Determination of chloramphenicol residues in milk, eggs, and tissues by liquid
      chromatography/mass spectrometry.
AB  - A new liquid chromatography/mass spectrometry (LC/MS) method is presented for the
      determination of chloramphenicol (CAP) residues in milk, eggs, chicken muscle and
      liver, and beef muscle and kidney. CAP is extracted from the samples with
      acetonitrile and defatted with hexane. The acetonitrile extracts are then
      evaporated, and residues are reconstituted in 10mM ammonium acetate--acetonitrile
      mobile phase and injected into the LC system. CAP is determined by reversed-phase
      chromatography using an Inertsil ODS-2 column and MS detection with negative ion
      electrospray ionization. Calibration curves were linear between 0.5-5.0 ng/g for
      all matrixes studied. The relative standard deviations for measurements by this
      method were generally <12%, and average recoveries ranged from 80 to 120%,
      depending on the matrix involved. The method detection limits of CAP ranged from
      0.2 to 0.6 ng/g, which are comparable to previously reported results. The
      proposed method is rapid, simple, and specific, allowing a single analyst to
      easily prepare over 40 samples in a regular working day.

PMID- 15859094
TI  - Simultaneous determination of methylmercury and ethylmercury in rice by capillary
      gas chromatography coupled on-line with atomic fluorescence spectrometry.
AB  - A comprehensive method for simultaneous determination of methylmercury (MeHg) and
      ethylmercury (EtHg) in rice by capillary gas chromatography (GC) coupled on-line
      with atomic fluorescence spectrometry was developed. The experimental conditions,
      including the pyrolyzer temperature and flow rates of the make-up gas and sheath
      gas, were optimized in detail. The absolute detection limits (3sigma) were 0.005
      ng as Hg for both MeHg and EtHg. The relative standard deviation values (n=5) for
      10 ng Hg/mL of MeHg and EtHg were 2.5 and 1.3%, respectively. The method was
      evaluated by analyzing 2 certified reference materials (DORM-2 and GBW08508), and
      the determined values of MeHg and total mercury concentrations were in good
      agreement with the certified values. In addition, the recoveries of MeHg and EtHg
      spiked into a rice sample collected from Jiangsu province in China were 86 and
      77%, respectively. The proposed method was applied to analysis of MeHg and EtHg
      in 25 rice samples cultivated in 15 provinces of China. In all samples, MeHg was
      detectable and no EtHg was found. The MeHg contents in rice samples ranged from
      1.9 to 10.5 ng/g, accounting for 7-44% of the total mercury measured.

PMID- 15859095
TI  - Isoelectric focusing identification of four freshwater fish commercially labeled
      "perch".
AB  - Isoelectric focusing (IEF) was used to distinguish 4 freshwater fish species that
      are sold in the European Union under the generic label of "perch": Perca
      fluviatilis (European perch), Lates niloticus (Nile perch), Stizostedion
      lucioperca (European pikeperch), and Morone chrysops x saxatilis (Sunshine bass).
      These species have different commercial values but are easily interchangeable
      because they are sold already filleted, in view of the numerous bones of the
      whole fish. IEF of the water-soluble proteins extracted from fish muscle resulted
      in species-specific patterns. None of the bands was common to all 4 species.
      Intraspecies polymorphism was low and did not concern the bands identified as
      characteristic of the species.

PMID- 15859096
TI  - Impact of hazardous waste regulations.

PMID- 15859097
TI  - Healthcare infection concerns debated.

PMID- 15859098
TI  - Meeting critical control needs.

PMID- 15859099
TI  - Filtering out airborne bacteria.

PMID- 15859100
TI  - Supporting growth of digital imaging.
AB  - Today's digital imaging industry has come very far for hospitals. The basic
      technology is ready, and hospitals are now acquiring, viewing, and storing more
      and more of their images digitally. The problem is--all of this is still only
      happening inside the radiology room. What's needed now for digital imaging to
      realise its full potential--both in cost savings and in improved patient care--is
      a supporting infrastructure of hardware, software and service options that
      extends image viewing outside of the radiology room and into the rest of the
      hospital. In fact, two of the most critical components for the widespread
      distribution of images are firstly, the availability of viewing hardware
      (especially DICOM-calibrated displays) whose cost and features are tailored to
      each user environment, and secondly, the ability for hospitals to manage this
      distributed hardware and provide quality assurance from one centralised location.

PMID- 15859102
TI  - Valuable insight into floor vibration.

PMID- 15859101
TI  - Bio-deactivation of hospital pathogens.

PMID- 15859103
TI  - Ensuring continuity in hot water delivery.

PMID- 15859105
TI  - Don't let obsession with numbers take your eyes off your goals.
AB  - The proliferation of comparative databases doesn't mean rankings have gained in
      significance. Good benchmarking requires achieving a balance that incorporates
      quality, cost, and speed. Measure success by the positive changes you have made
      and whether you're reaching your goals.

PMID- 15859104
TI  - Enhancing access for the disadvantaged.

PMID- 15859106
TI  - Blood glucose monitoring slashes mortality rates.
AB  - Gaining buy-in of intensive care unit nurses was critical to the success of the
      initiative. Complex diabetes treatment issues required leaving some decisions to
      bedside nurses. Projects success leads to implementation in hospital's special
      care unit.

PMID- 15859107
TI  - Universal protocol cuts hip surgery fatalities.
AB  - Root-cause analysis employed to determine best way to proceed. Medical management
      department takes lead role in developing new protocol. New privileging
      requirements established for those conducting pre-op assessments.

PMID- 15859108
TI  - 33% of fatal med errors involve insulin therapy.
AB  - Use of computers seen as critical to successful error reduction initiatives.
      Building teamwork takes time, money, and resources--but it's worth it.
      Educational efforts must be customized to fit the patient's socioeconomic and
      educational background.

PMID- 15859109
TI  - Know differences between kids and adults: cut errors.
AB  - One of every 100 patients has an adverse event; 60% of those were deemed to be
      preventable. Birth-related, diagnosis-related, system-related errors greatest
      contributors to adverse events. Very little pediatric data are available on
      medical errors; more research is called for.

PMID- 15859110
TI  - 'Quality plus' gains 39 early participants.

PMID- 15859111
TI  - The EU-project ERAPharm. Incentives for the further development of guidance
      documents?
AB  - Triggered by the detection of a large variety of pharmaceuticals in surface
      waters, soils and groundwaters across the world (e.g. Halling-Sorensen et al.
      1998, Daughton & Ternes 1999, Jones et al. 2001, Heberer 2002) and the widespread
      occurrence of endocrine active compounds and related effects in the environment
      (e.g. Purdom et al. 1994, Tyler et al. 1998, Vethaak et al. 2002),
      pharmaceuticals in the environment have become an issue for both the scientific
      and the public community. During the last few years, our understanding of the
      fate and effects of pharmaceuticals in the environment has progressed
      significantly. However, there are still a number of uncertainties concerning the
      effects of pharmaceuticals on the environment and the assessment of potential
      exposure (e.g. Hanisch et al. 2004, Salomon 2005). These uncertainties will be
      addressed by the EU-project 'Environmental risk assessment of pharmaceuticals'
      (ERAPharm). This project, a specific targeted research project, is carried out
      within the priority 'Global change and ecosystems' of the 6th framework programme
      of the European Union. ERAPharm has started on 1st October 2004; the project
      duration is three years.

PMID- 15859112
TI  - Measurement of the oxygen mass transfer through the air-water interface.
AB  - GOAL, SCOPE AND BACKGROUND: Gas mass transfer through the liquid-gas interface
      has enormous importance in various natural and industrial processes. Surfactants
      or insoluble compounds adsorbed onto an interface will inhibit the gas mass
      transfer through the liquid-gas surface. This study presents a technique for
      measuring the oxygen mass transfer through the air-water interface. Experimental
      data obtained with the measuring device were incorporated into a novel
      mathematical model, which allowed one to calculate diffusion conduction of liquid
      surface layer and oxygen mass transfer coefficient in the liquid surface layer.
      METHODS: A special measurement cell was constructed. The most important part of
      the measurement cell is a chamber containing the electrochemical oxygen sensor
      inside it. Gas exchange between the volume of the chamber and the external
      environment takes place only through the investigated surface layer. Investigated
      liquid was deoxygenated, which triggers the oxygen mass transfer from the chamber
      through the liquid-air interface into the liquid phase. The decrease of oxygen
      concentration in the cell during time was measured. By using this data it is
      possible to calculate diffusional parameters of the water surface layer. RESULTS:
      Diffusion conduction of oxygen through the air-water surface layer of selected
      wastewaters was measured. The diffusion conduction of different wastewaters was
      about 3 to 6 times less than in the unpolluted water surface. It was observed
      that the dilution of wastewater does not have a significant impact on the oxygen
      diffusion conduction through the wastewater surface layer. This fact can be
      explained with the presence of the compounds with high surface activity in the
      wastewater. Surfactants achieved a maximum adsorption and, accordingly, the
      maximum decrease of oxygen permeability already at a very low concentration of
      surfactants in the solution. Oxygen mass transfer coefficient of the surface
      layer of the water is found to be Ds/ls = 0.13 x 10(-3) x cm/s. CONCLUSION: A
      simple technique for measuring oxygen diffusion parameters through the air-water
      solution surface has been developed. Derived equations enable the calculation of
      diffusion parameters of the surface layer at current conditions. These values of
      the parameters permit one to compare the resistances of the gas-liquid interface
      to oxygen mass transfer in the case of adsorption of different substances on the
      surface layer. RECOMMENDATION AND OUTLOOK: This simple technique may be used for
      a determination of oxygen permeability of different water-solution surface
      layers. It enables one to measure the resistance to the oxygen permeability of
      all inflowing wastewater surface layers in the wastewater treatment plant, and to
      initiate a preliminary cleaning of this wastewater if required. Similarly, we can
      measure oxygen permeability of natural waterbodies. Especially in the case of
      pollution, it is important to know to what extent the oxygen permeability of the
      water surface layer has been decreased. Based on the tehnique presented in this
      research, fieldwork equipment will be developed.

PMID- 15859113
TI  - Bioaccumulation of elements in bryophytes from Serra da Estrela, Portugal, and
      Veluwezoom, the Netherlands.
AB  - BACKGROUND, AIMS AND SCOPE: Pollution by heavy metals over large areas and long
      periods of time may cause chronic damage to living organisms and must be
      carefully controlled. One way to determine the extent of environmental
      contamination is by measuring the levels of contaminants in plants. The use of
      mosses as biomonitors is a convenient method to determine levels of (atmospheric)
      deposition, as terrestrial mosses obtain most of their supply of mineral elements
      from precipitation and dry deposition of airborne particles. Mosses have
      therefore received increasing attention as a suitable tool for monitoring
      regional patterns of elemental deposition from the atmosphere in large-scale
      studies in various countries, in areas close to industrial installations as well
      as in areas not expected to be contaminated. Although this technique is widely
      known, ecological studies of this type have rarely been done in Portugal. The aim
      of this paper is to evaluate and compare the spatial distribution of heavy metals
      in Hypnum cupressiforme, Pleurozium schreberi, Dicranum scoparium and Polytrichum
      piliferum collected from the Serra da Estrela natural park in Portugal and in the
      Veluwezoom natural park in the Netherlands. The selected species are the most
      widely used bryophytes for biomonitoring in the boreal region. The popularity of
      these species for this purpose is due to their wide ecological amplitude and
      distribution. METHODS: At 54 sampling sites in both nature parks, samples of
      Hypnum cupressiforme, Pleurozium schreberi, Dicranum scoparium and Polytrichum
      piliferum were collected. Plant digests were analysed for Al, Ba, Ca, Cr, Fe, K,
      Mg, Mn, Ni, Sr, V, Zn, Pb, Cu, Cd, N and P. Differentiations between sampling
      sites in terms of concentrations of elements in mosses were evaluated by ANOVA
      and the least significant difference was calculated. The normality of the
      analysed features was checked with the chi square test. After standardization,
      the matrix of 54 samples and 10 heavy metals was subjected to numerical
      classification to detect groups of samples with similar patterns of metal
      concentrations. The clustering algorithm was prepared with Ward's method, and the
      City Block Manhattan method was used for the similarity measure. Metals and
      samples were also subjected to ordination to reveal possible gradients of heavy
      metal levels, using PCA. Correlations were calculated between concentrations of
      metals and factors 1 and 2, allowing the dependence between the concentration of
      metals and factors (factor loading) to be estimated. RESULTS AND DISCUSSION: All
      species examined in both areas contained elevated levels of Mn and Pb. For each
      particular species, concentrations of N, P and Pb were significantly higher at
      Serra da Estrela, while concentrations of Cu were significantly higher at the
      Veluwezoom. Mosses from Portugal and the Netherlands differed significantly
      mainly in the concentrations of Al, Ba, Cr, Fe, Mn, Ni, Pb and V. This
      differentiation did not exceed that within the mosses from Portugal. CONCLUSIONS:
      Mosses from Portugal and the Netherlands differ significantly mainly in the
      concentrations of Al, Ba, Cr, Fe, Mn, Ni, Pb and V. This differentiation does not
      exceed the differentiation within the mosses from Portugal. RECOMMENDATION AND
      OUTLOOK: Further research is required into the origin and deposition of the
      polluting elements in other environmental compartments.

PMID- 15859114
TI  - Cumulative and residual effects of repeated sewage sludge applications: forage
      productivity and soil quality implications in South Florida, USA.
AB  - BACKGROUND, AIM AND SCOPE: The cow-calf (Bos taurus) industry in subtropical
      United States and other parts of the world depends almost totally on grazed
      pastures. Establishment of complete, uniform stand of bahiagrass (BG) in a short
      time period is important economically. Failure to obtain a good BG stand early
      means increased encroachment of weeds and the loss of not only the initial
      investment costs, but production and its cash value. Forage production often
      requires significant inputs of lime, N fertilizer, and less frequently of P and K
      fertilizers. Domestic sewage sludge or biosolids, composted urban plant debris,
      waste lime, phosphogypsum, and dredged materials are examples of materials that
      can be used for fertilizing and liming pastures. Perennial grass can be a good
      choice for repeated applications of sewage sludge. Although sewage sludge supply
      some essential plant nutrients and provide soil property-enhancing organic
      matter, land-application programs still generate some concerns because of
      possible health and environmental risks involved. The objectives of this study
      were to evaluate the cumulative and residual effects of repeated applications of
      sewage sludge on (i) bahiagrass (BG, Paspalum notaturn Flugge) production over
      years with (1997-2000) and without (2001-2002) sewage sludge applications during
      a 5-yr period, and (ii) on nutrients status of soil that received annual
      application of sewage sludge from 1997 to 2000 compared with test values of soils
      in 2002 (with no sewage sludge application) in South Florida. METHODS: The field
      experiment was conducted at the University of Florida Agricultural Research and
      Education Center, Ona, FL (27 degrees 26'N, 82 degrees 55'W) on a Pomona fine
      sandy soil. With the exception of the control, BG plots received annual sewage
      sludge and chemical fertilizers applications to supply 90 or 180 kg total N ha(
      1) yr(-1) from 1997 to 2000. Land application of sewage sludge and fertilizer
      ceased in 2001 season. In early April 1998, 1999, and 2000, plots were mowed to 5
      cm stubble and treated with the respective N source amendments. The experimental
      design was three randomized complete blocks with nine N-source treatments:
      ammonium nitrate (AMN), slurry biosolids of pH 7 (SBS7), slurry biosolids of pH
      11 (SBS11), lime-stabilized cake biosolids (CBS), each applied to supply 90 or
      180 kg N ha(-1), and a nonfertilized control (Control). Application rates of
      sewage sludge were calculated based on the concentration of total solids in
      materials as determined by the American Public Health Association SM 2540G method
      and N in solids. The actual amount of sewage sludge applications was based on the
      amount required to supply 90 and 180 kg N ha(-1). Sewage sludge materials were
      weighed in buckets and uniformly applied to respective BG plots. Soil samples
      were collected in June 1997, June 1999, and in June 2002 from 27 treatment plots.
      In 1997 and 1999, soil samples were collected using a steel bucket type auger
      from the 0- to 20-, 20- to 40-, 40- to 60-, and 60- to 100-cm soil depths. Forage
      was harvested on 139, 203, 257, and 307 day of year (DOY) in 1998; 125, 202, 257,
      and 286 DOY in 1999; 179, 209, 270, and 301 DOY in 2000; and on 156 and 230 DOY
      in 2002 (no sewage sludge applications) to determine the residual effect of
      applied sewage sludge following repeated application. Forage yield and soils data
      were analyzed using analysis of variance (PROC ANOVA) procedures with year and
      treatment as the main plot and sub-plot, respectively. As a result of significant
      year effects on forage yield, data were reanalyzed annually (i.e., 1998, 1999,
      2000, and 2002). RESULTS AND DISCUSSION: All sewage sludges used in this study
      were of class B in terms of USEPA's pathogens and pollutant concentration limit.
      Pathogen and chemical composition of the class B sewage sludge that were used in
      the study were all in compliance with the USEPA guidelines. The liquid sludge
      (SBS11) had the lowest fecal coliform counts (0.2 x 10(6) CFU kg(-1)) while the
      cake sewage sludge (CBS) had the greatest coliform counts of 178 x 10(6) CFU kg(
      1). The fecal coliform counts for SBS7 was about 33 x 10(6) CFU kg(-1). Average
      soil test values in June 2002 exhibited: i) decrease in TIN (NO3-N + NH4-N), TP,
      K, Ca, Mg, Mn, and Fe; and ii) slight increase in Zn and Cu when compared with
      the June 1997 soil test results. The overall decrease in soil test values in 2002
      might be associated with nutrient cycling and plant consumption. Although the
      average BG forage yield in 2002 (2.3 +/- 0.7 Mg ha(-1)) was slightly lower than
      in 2000 (3.5 +/- 1.2 Mg ha(-1)), yield differences in 2002 between the control
      (1.2 +/- 0.2 Mg ha(-1)) and treated plots (2.3 +/- 0.5 Mg ha(-1) to 3.3 +/- 0.6
      Mg ha(-1)) were indicative of a positive residual effect of applied sewage
      sludge. This study has shown that excessive build up of plant nutrients may not
      occur in beef cattle pastures that repeatedly received sewage sludge while
      favoring long-term increased forage yield of BG. All sources of N (sewage sludge
      and AMN) gave better forage production than the unfertilized control during years
      with sewage sludge application (1997-2000) and also during years with no sewage
      sludge application (2001-2002). The favorable residual effects of applied sewage
      sludge in 2002 may have had received additional boost from the amount of rainfall
      in the area. CONCLUSIONS: Repeated applications of sewage sludge indicate no
      harmful effects on soil quality and forage quality. Our results support our
      hypothesis that repeated land application of sewage sludge to supply 90 and 180
      kg N ha(-1) would not increase soil sorption for nutrients and trace metals.
      Results have indicated that the concentrations of soil TIN and TP declined by
      almost 50% in plots with different nitrogen sources from June 1997 to June 2002
      suggesting that enrichment of nitrogen and phosphorus is insignificant. The
      concentrations of soil nitrogen and phosphorus in 2002 following repeated
      application of sewage sludge were far below the contamination risk in the
      environment. The residual effect of these sewage sludge over the long term can be
      especially significant in many areas of Florida where only 50% of the 1 million
      ha of BG pastures are given inorganic nitrogen yearly. RECOMMENDATION AND
      OUTLOOK: Successive land application of sewage sludge for at least three years
      followed by no sewage sludge application for at least two years may well be a
      good practice economically because it will boost and/or maintain sustainable
      forage productivity and at the same time minimize probable accumulation of
      nutrients, especially trace metals. Consecutive applications of sewage sludge may
      result in build up of some trace metals in some other states with initial high
      metallic content, but in this study, no detrimental effects on soil chemical
      properties were detected. The possibilities for economically sound application
      strategies are encouraging, but more and additional research is required to find
      optimal timing and rates that minimizes negative impacts on soil quality in
      particular or the environment in general. For proper utilization of sewage
      sludge, knowledge of the sewage sludges' composition, the crop receiving it, are
      absolutely crucial, so that satisfactory types and rates are applied in an
      environmentally safe manner. There is still much to be learned from this study
      and this investigation needs to continue to determine whether the agricultural
      and ecological objectives are satisfied over the longer term.

PMID- 15859115
TI  - Natural pollution caused by the extremely acidic crater lake Kawah Ijen, East
      Java, Indonesia.
AB  - BACKGROUND, AIMS AND SCOPE: Lakes developing in volcano craters can become highly
      acidic through the influx of volcanic gases, yielding one of the chemically most
      extreme natural environments on earth. The Kawah Ijen crater lake in East Java
      (Indonesia) has a pH < 0.3. It is the source of the extremely acidic and metal
      polluted river Banyupahit (45 km). The lake has a significant impact on the river
      ecosystem as well as on a densely populated area downstream, where agricultural
      fields are irrigated with water with a pH between 2.5 and 3.5. The chemistry of
      the river water seemed to have changed over the past decade and the negative
      effect in the irrigation area increased. A multidisciplinary approach was used to
      investigate the altered situation and to get insight in the water chemistry and
      the hydrological processes influencing these alterations. Moreover, a first
      investigation of the effects of the low pH on ecosystem health and human health
      was performed. METHODS: Water samples were taken at different sites along the
      river and in the irrigation area. Sampling for macroinvertebrates was performed
      at the same sites. Samples of soil and crop were taken in the irrigation area.
      All samples were analysed for metals (using ICP-AES) and other elements, and
      concentrations were compared to local and international standards. RESULTS AND
      DISCUSSION: The river carries a very high load of SO4, NH4, PO4, Cl, F, Fe, Cu,
      Pb, Zn, Al and other potentially toxic elements. Precipitation and discharge data
      over the period of 1980-2000 clearly show that the precipitation on the Ijen
      plateau influences water chemistry of the downstream river. Metal concentrations
      in the river water exceed the concentrations mentioned in Indonesian and
      international quality guidelines, even in the downstream river and the irrigation
      area. Some metal concentrations are extremely high, especially iron (up to 1,600
      mg/l) and aluminium (up to 3,000 mg/l). The food-webs in the acidic parts of the
      river are highly underdeveloped. No invertebrates were present in the extremely
      acidic water and, at pH 2.3, only chironomids were found. This also holds true
      for the river water with pH 3.3 in the downstream area. Agricultural soils in the
      irrigation area have a pH of 3.9 compared to a pH of 7.0 for soils irrigated with
      neutral water. Decreased yields of cultivated crops are probably caused by the
      use of Al containing acidic irrigation water. Increased levels of metals
      (especially Cd, Co, Ni and Mn) are found in different foodstuffs, but still
      remain within acceptable ranges. Considering local residents' diets, Cd levels
      may lead to an increased risk for the human health. Fluoride exposure is of
      highest concern, with levels in drinking water exceeding guideline values and a
      lot of local residents suffering from dental fluorosis. CONCLUSIONS,
      RECOMMENDATIONS AND OUTLOOK: In short, our data indicate that the Ijen crater
      lake presents a serious threat to the environment as well as human health and
      agricultural production.

PMID- 15859116
TI  - Using a set of strategic indicator systems as a decision-making support implement
      for establishing a recycling-oriented society. A Taiwanese case study.
AB  - BACKGROUND, SCOPE AND AIMS: To realize the vision of sustainable development (SD)
      originating from the 'only one earth' philosophy, and to integrate the
      conceptions of ecology and sustainability into the planning and decision-making
      criteria of urban growth management, the establishment of a recycling-oriented
      society (ROS) is essential. However, before the above intention can be achieved,
      it is indispensable to develop a system of strategic indicators for supporting a
      radical reformation of the urban development plan. Therefore, this study, based
      on the conception of the new urban development pattern ROS, attempted to
      carefully choose a sample city in Taiwan for launching a preliminary case study,
      and furthermore designed and proposed a concise and strategy-oriented assessment
      indicator system termed ROSAIS. ROSAIS, on the one hand, can act as a compass for
      understanding resource using efficiency and recycling status during city
      development and, on the other hand, can serve as an implement supporting decision
      making for ROS construction. METHODS: According to the definition and spirit of
      ROS, the structure of ROSAIS should clearly represent the relationship between
      resources and environment in human activities. The eco-efficiency indicator
      system (EEIS) and environmental symbiosis indicator system (ESIS) can be
      considered two key subindicator systems, and are the necessary components of
      ROSAIS. EEIS chooses the dominant production sectors in urban economic activities
      to calculate their eco-efficiency (EE). Separately, for obtaining a consensus
      regarding the framework of ESIS, the questionnaire approaches and expert
      consultation, together with the research experience and foundation of current
      relevant studies and indicator systems, are applied when crucial resource and
      environmental issues and respective indicators are selected. RESULTS AND
      DISCUSSION: The calculation results of EEIS in this case study indicated that
      among the three dominant production activities (agricultural, fishery, and animal
      husbandry sector) the fishery sector has the highest EE, which indicates that the
      fishery activities and resources significantly influence the sustainability of
      the economic-environmental system of the sample city. Furthermore, according to a
      consensus achieved in ESIS, local green spaces, resource recovery, energy
      consumption pattern change, freshwater conservation and greenhouse effect
      abatement were considered as the five crucial issues influencing how the case
      study city can develop into an ES-city. The rate of local green spaces, resource
      recycling, freshwater conservation and the rate of reduction of nonrenewable
      energy use as well as carbon dioxide (CO2) emissions were used to evaluate the
      above five issues. CONCLUSION: This case study is unparalleled in Taiwan. Even in
      Japan, where ROS legislation has been implemented, this kind of study remains in
      the preliminary stages. Furthermore, when communicating the indicator results, it
      is essential to provide the context and countermeasures of the crucial issues
      that are faced. The two sub-indicator systems proposed in this case study could
      comply completely with the above-mentioned requirements. For example, the EEIS
      provides information for achieving a balance between environmental burden and
      economic benefits among dominant production sectors; the ESIS provides
      information for setting strategies for overcoming the crucial issues faced.
      RECOMMENDATION AND OUTLOOK: This study recommends that urban planers should
      consider the construction of the corresponding strategic indicator system to be
      indispensable, and makes further use of the indicator results related to the
      environmental education of residents for identifying and promoting participation
      with ROS, and turning them into implements for supporting urban SD decision
      making. Furthermore, a successful indicator system depends on data availability
      and quality. This study recommends that urban planers should pay considerable
      attention to constructing relevant data collection channels, databases and the
      data quality.

PMID- 15859117
TI  - Phytotoxicity of cyanide to weeping willow trees.
AB  - BACKGROUND: Cyanide is found predominantly in industrial effluents generated by
      metallurgical operations. It is an extremely toxic compound, so that problems and
      catastrophic accidents have recently occurred all around the globe. The goal of
      this study was to determine the toxicity of cyanide to a Chinese willow species,
      and to determine the removal capacity. METHODS: The toxicity of potassium cyanide
      (KCN) to weeping willow trees (Salix babylonica L.) was tested. The normalized,
      relative transpiration of the plants was used to determine the phytotoxicity of
      cyanide. The cyanide removal capacity of weeping willows was also determined.
      RESULTS AND DISCUSSION: In hydroponic solution, no chlorosis of leaves and only a
      small reduction in normalized relative transpiration was observed when weeping
      willows were exposed to low doses of cyanide (< or = 0.93 mg CN/L). Severe signs
      of toxicity were found for the treatment groups exposed to higher doses of
      cyanide (> or = 9.3 mg CN/L). Weeping willows grown in sandy soils survived the
      entire period (216 hours) without any toxic effect when irrigated with low doses
      of cyanide (3.72 mg CN/L). High doses of cyanide (> or = 18.6 mg CN/L) in
      irrigation water were fatal for the weeping willows within 216 hours. EC50 values
      for a 50% inhibition of the transpiration of the trees were estimated to be
      between 3.27 and 8.23 mg CN/L, depending on the duration of the exposure.
      CONCLUSIONS: The results obtained for the Chinese willow species Salix babylonica
      were very similar to those obtained for the European species S. viminalis in
      earlier studies. Phytotoxic effects were only found at high doses of cyanide. A
      large proportion of applied cyanide was removed from the contaminated media in
      the presence of weeping willows. This gives rise to the conclusion that the
      metabolism of cyanide by weeping willows is possible. RECOMMENDATIONS AND
      OUTLOOK: Cyanide elimination with trees seems to be a feasible option for
      cleaning soils and water contaminated with cyanide. A full-scale treatment has
      been installed in Denmark. For phytoremediation projects in China, weeping willow
      could be a suitable species. The tree can tolerate and remove cyanide, and it is
      a native Chinese species. Besides, the tree is of outstanding beauty and is
      planted as a common park tree in many parts of the world.

PMID- 15859118
TI  - A new challenge for developing countries--Egypt.

PMID- 15859119
TI  - The U.S. experience in promoting sustainable chemistry.
AB  - BACKGROUND, AIM AND SCOPE: Recent developments in European chemicals policy,
      including the Registration, Evaluation and Authorization of Chemicals (REACH)
      proposal, provide a unique opportunity to examine the U.S. experience in
      promoting sustainable chemistry as well as the strengths and weaknesses of
      existing policies. Indeed, the problems of industrial chemicals and limitations
      in current regulatory approaches to address chemical risks are strikingly similar
      on both sides of the Atlantic. We provide an overview of the U.S. regulatory
      system for chemicals management and its relationship to efforts promoting
      sustainable chemistry. We examine federal and state initiatives and examine
      lessons learned from this system that can be applied to developing more
      integrated, sustainable approaches to chemicals management. MAIN FEATURES: There
      is truly no one U.S. chemicals policy, but rather a series of different un
      integrated policies at the federal, regional, state and local levels. While
      centerpiece U.S. Chemicals Policy, the Toxic Substances Control Act of 1976, has
      resulted in the development of a comprehensive, efficient rapid screening process
      for new chemicals, agency action to manage existing chemicals has been very
      limited. The agency, however, has engaged in a number of successful, though
      highly underfunded, voluntary data collection, pollution prevention, and
      sustainable design programs that have been important motivators for sustainable
      chemistry. Policy innovation in the establishment of numerous state level
      initiatives on persistent and bioaccumulative toxics, chemical restrictions and
      toxics use reduction have resulted in pressure on the federal government to
      augment its efforts. RESULTS AND CONCLUSIONS: It is clear that data collection on
      chemical risks and phase-outs of the most egregious chemicals alone will not
      achieve the goals of sustainable chemistry. These alone will also not internalize
      the cultural and institutional changes needed to ensure that design and
      implementation of safer chemicals, processes, and products are the focus of the
      future. Thus, a more holistic approach of 'carrots and sticks'--that involves not
      just chemical producers but those who use and purchase chemicals is necessary.
      Some important lessons of the US experience in chemicals management include: (1)
      the need for good information on chemicals flows, toxic risks, and safer
      substances.; (2) the need for comprehensive planning processes for chemical
      substitution and reduction to avoid risk trade-offs and ensure product quality;
      (3) the need for technical and research support to firms for innovation in safer
      chemistry; and (4) the need for rapid screening processes and tools for
      comparison of alternative chemicals, materials, and products.

PMID- 15859120
TI  - [Factors related to the demand of caregivers for institutionalization of disabled
      persons living at home].
AB  - PURPOSE: Recently, there has been an increase in the number of caregivers who are
      demanding institutionalization of the disabled, despite having taken care of them
      at home since their birth. It is important to clarify the background of this
      demand in order to help develop plans aimed at socially supporting the
      caregivers. This study was aimed at elucidating the factors related to demands of
      caregivers to have disabled persons living at home institutionalized. METHODS: To
      caregivers of 410 home-living disabled persons, we handed out and collected
      questionnaires asking for the following information: age of the disabled persons
      and their caregivers, severity of the disability, status and level of
      manageability of the caregivers, and the place where the caregivers wanted the
      disabled to live in the future. The demand for institutionalization of the
      disabled and the attributes of the responders were analyzed by multiple logistic
      regression. RESULTS: From the responses of 297 people who replied to the
      questions, univariate analysis revealed that the demand for institutionalization
      significantly correlated with the labels of "severe" in the mental disability
      certificate, "incapable of conversation" according to the Office of Population
      Censuses and Surveys (OPCS) scale, "severe disability" in Oshima's classification
      and "unfit" and "unable to give daily care." The results analyzed by multiple
      logistic regression revealed that older caregivers had a significantly higher
      odds ratio (18.3 for those in their 40s and 37.2 for those in their 50s),
      indicating a strong correlation between the demand for institutionalization and
      the age of the caregivers. According to the mental disability certificate, the
      odds ratio of those with "A" was 5.0 relative to "other than A," while the odds
      ratio was 3.8 for those "unable to give care" against "able to give care," in
      both cases statistically significant. As for suffering in daily life, a majority
      of the caregivers aged 50 years or older claimed "a limit to home caring" and
      "aging". Regarding the shortage of public welfare services, a large percentage
      pointed out the inconveniences of emergency short stay, short stay, day care, and
      bathing services. CONCLUSION: The factors related to demand for
      institutionalization of disabled care receivers at home were aging of the
      caregivers, incapability of giving daily care, and severe mental impairment. The
      age of the caregivers was identified as an explicit factor.

PMID- 15859121
TI  - [Risk factors for requiring long-term care among middle-aged and elderly people].
AB  - OBJECTIVE: The purpose of this study is to clarify risk factors for requiring
      long-term care and all-cause mortality among middle-aged and elderly people.
      METHODS: The subjects were 2292 residents (759 males and 1,533 females) living in
      rural areas and attending health checkups during 1989-1993. Using the data
      obtained, we examined risk factors for long-term care needs and all-cause
      mortality. The observation period was from health checkups to March 2002 for all
      cause mortality and to September 2002 for long-term care. The Cox' proportional
      hazards model was used to assess for both outcomes. RESULTS: Although all-cause
      mortality was two and a half times as high among males as among females, there
      were no differences between the sexes in the rate for requiring long-term care.
      In thirty five percent of cases needing long-term care, this was attributable to
      cerebrovascular diseases, in 24% to dementia, and in 9% to fracture. Risk factors
      significantly associated with higher all-cause mortality were age, low BMI, low
      total cholesterol, liver dysfunction, and smoking among males and females, as
      well as urine sugar among males and anemia among females. Risk factors
      significantly associated with requiring long-term care were age, hypertension and
      urine sugar among males, and age, anemia and urine sugar among females.
      CONCLUSIONS: This study shows that control of hypertension and diabetes mellitus
      is important for avoiding necessity for long-term care.

PMID- 15859122
TI  - [Factors related to breakfast eating behavior among elementary school children].
AB  - OBJECT: The purpose of this study was to clarify factors related to eating
      breakfast among elementary school children. METHOD: The subjects were 196 fifth
      grade pupils from two elementary schools in Osaka Prefecture. The main survey
      items were as follows: Number of eating breakfast days in the last week, appetite
      for breakfast, sleeping habits, knowledge on food, attitude related to eating
      breakfast, self-esteem, social skills, and eating behavior of family members. The
      Rosenberg Scale was used to measure global self-esteem and the Pope Scale for
      estimation of family-related self-esteem. Social skills were assessed using the
      scale developed by Shimada et al., which consists of subscales for pro-social
      skills, withdrawal behavior, and aggressive behavior. RESULTS: The main results
      were as follows: (1) The percentages of children who ate breakfast everyday in
      the last week were 78.3% for boys and 70.2% for girls, who no significant
      difference between the sexes. (2) The children who ate breakfast everyday in the
      last week (everyday-eating group) had more appetite for breakfast and went to bed
      earlier than the children who one or more days without eating (lack-of-eating
      group). (3) Compared with the lack-of-eating group, the everyday-eating group
      showed higher scores in family-related self-esteem and pro-social skills, and
      lower scores for aggressive behavior. (4) Regarding knowledge on food except
      influence of sugar for health, there were no differences between the everyday
      eating and lack-of-eating groups. However, the former included more children who
      thought that eating every breakfast was very important, compared with the latter.
      (5) Children who expressed the following answers were more abundant in the
      everyday-eating group than in the lack-of-eating group: (1) Family members
      prepare breakfast every day; (2) They ate breakfast with family members everyday
      in the last week; (3) They often talk with family members during meals and
      snacks. CONCLUSIONS: From the above results, the following are suggested in
      relation to the development of eating breakfast for elementary school children:
      (1) Only providing knowledge on nutrition is insufficient; (2) Development of a
      positive attitude toward the significance of breakfast is necessary; (3)
      Development of a daily living rhythm, including sleeping behavior, is important;
      (4) Encouraging the development of family-related self-esteem and the social
      skills is important. Therefore, especially in the elementary school stage, not
      only conducting eating behavior education at school, but also intervention to
      affect family members' behavior and attitudes has an important role.

PMID- 15859123
TI  - [Scale for assessing interests of Japanese elderly people in their daily life].
AB  - OBJECTIVE: Programs to support independent living for elderly people are
      generally designed taking into account physical and psychological conditions. The
      interests of individuals are diverse even when the physical conditions are the
      same. Interests in daily life are important factors for adequate planning of the
      programs for independent living. The purpose of this study was to examine an
      evaluation structure of interests of Japanese elderly people in their daily life.
      METHODS: Focus group interviews were conducted to collect items for interests in
      daily life by several researchers targeting activity groups of elderly people.
      Eighteen items were extracted from a total of 50 following the principles: (1)
      Items with similar meanings are brought together; (2) Items which might have big
      differences in meaning depending on the subject were excluded; and (3) Items
      which were double barreled were excluded. The questionnaire 18 items were
      designed to give a 4-point Likart scale for answers from "very important" to "not
      important at all". The survey was conducted in 20 municipalities all over Japan
      in 2000. From residents aged 65 years and over, 6,094 individuals were selected
      randomly as the study population. RESULTS: Of 5,565 participants, 4,527
      individuals answered all 18 items. "To have a good time with the family" was the
      favorite answer (54.8%), rated as "very important". Four factors (eigenvalue > 1)
      were extracted by applying principal component analysis: "to live with good
      communication", "to achieve one's purpose", "to live socially", and "to live
      comfortably". "To live with good communication" showed the highest score and "To
      live socially" showed the lowest score. CONCLUSION: With this scale, we could
      precisely determine the diversity of interests of Japanese elderly people in
      their daily life. We suggest that this scale might be useful not only to analyze
      the interests of individuals, but also to plan programs in terms of quality of
      life or independent living in late life.

PMID- 15859124
TI  - [Questionnaire survey focused on utility and application of a mailing list of
      infectious disease prevalence information by the mailing method and the e-mail
      method].

PMID- 15859125
TI  - [Research regarding the current state of collaboration in community-based welfare
      advocacy programs].

PMID- 15859126
TI  - [Reminiscences: My life as a nephrologist].

PMID- 15859127
TI  - [Indication and contraindication in renal biopsy].

PMID- 15859128
TI  - [Informed-consent for renal biopsy].

PMID- 15859129
TI  - [Problems and perspectives for clinical organ xenotransplantation].

PMID- 15859130
TI  - [Gene therapy for kidney transplantation].

PMID- 15859131
TI  - [Flow cytometric analysis of mesothelial cells in peritoneal dialysis effluent].
AB  - According to recent reports, deformity and size of mesothelial cells reflect
      mesothelial condition. We applied flow cytometry (FCM) to the analyzation of
      mesothelial cells in peritoneal dialysis effluent (PDE) and the relationship
      between the period of peritoneal dialysis (PD) and peritoneal function. Eighteen
      patients treated for two to 89 months by PD were selected. Their dialysate:
      plasma creatinine ratio (D/P creatinine)was 0.67 +/- 0.086 (0.53 to 0.87).
      Overnight PDE was drained and centrifuged. The cell population of peritoneal
      cells identified by anti-cytokeratin, CD14 and 45 antibodies was studied by FCM.
      Cytokeratin positive cells were identified as mesothelial cells, distinct from
      macrophages, granulocytes or lymphocytes. The forward scatter (FSC) of
      cytokeratin positive cells, fluorescence intensity of cytokeratin and percentage
      of cytokeratin-positive cells in PDE were 395.6 +/- 55.5 (298.31 to 527.72),
      333.9 +/- 272.9 (67.55 to 1,071.95), and 6.75 +/- 6.1% (0.44 to 21.14),
      respectively. There was a positive correlation between D/P creatinine and FSC,
      and a negative correlation between D/P creatinine and cytokeratin fluorescence
      intensity or the percentage of cytokeratin positive cells. However, there was no
      correlation between the period of PD and FSC, cytokeratin fluorescence intensity
      or the percentage of cytokeratin-positive cells. It was suggested that the
      alteration of mesothelial cells is not necessarily influenced by the period of
      PD, but influences peritoneal function. It was found that the analysis of cell
      population by FCM reflects the morphological and functional changes in the
      peritoneum of patients on PD.

PMID- 15859132
TI  - [Changes in the clinical features of MPGN type-I in childhood over three
      decades].
AB  - This retrospective study was conducted to evaluate changes in the clinical
      features of MPGN type I in childhood during a 30-year period from 1970 through
      1999. Renal biopsies were performed on 2,260 children with glomerulonephritides,
      among whom were 71 patients with MPGN type-I. Changes in the mode of onset were
      investigated in patients separated according to the period of onset into two
      groups by 1974 in which school urinary screening had been widespread. The
      difference in symptoms after onset was examined between patients with the onset
      in the 1980s and 1990s under the same circumstances of school urinary screening
      and of our steroid regimen. Finally, the incidences of this disease in each of
      the three decades were analyzed. Chance proteinuria and/or hematuria increased
      (p=0.0107) and acute nephritic syndrome decreased (p=0.0237) in the ratio of the
      initial symptom on and after 1974. Regarding the clinical presentation after
      onset, non-nephrotic range proteinuria increased (p=0.0415) and nephrotic
      syndrome decreased (p=0.0415) in the 1990s, in comparison with the respective
      rates in the 1980s. The incidence of this disease decreased (p<0.01) in
      chronological order. CONCLUSION: The clinical features of this disease definitely
      changed over three decades suggesting that the clinical presentation has
      ameliorated in recent years, regardless of effective palliation of severe
      symptoms afforded by our steroid regimen.

PMID- 15859133
TI  - [A case of chronic renal failure complicated with tuberculous meningitis
      successfully diagnosed by nested polymerase chain reaction (PCR)].
AB  - A 44 year-old woman was diagnosed as having chronic renal failure due to rapidly
      progressive glomerulonephritis (RPGN) from one year earlier. She has been managed
      with steroid therapy and hemodialysis. The patient was admitted to our hospital
      because of fever and sudden disturbance of consciousness with generalized
      convulsion on October 30, 2003. She showed mild meningeal irritation.
      Cerebrospinal fluid (CSF) examination demonstrated a cell count of 60/microl,
      protein level of 70 mg/dl, glucose level of 52 mg/dl, and chloride (Cl) level of
      116 mEq/l. Both the CSF culture for Mycobacterium (M.) tuberculosis and the
      conventional single polymerase chain reaction (PCR) for M. tuberculosis DNA in
      CSF were negative results on admission. In contrast, nested PCR of preserved CSF
      samples obtained at admission demonstrated positive results. We diagnosed her
      conditions as tuberculous meningitis (TBM) and administered a total of 3 anti
      tuberculosis agents over a period of about 2 months. Her clinical condition and
      CSF examinations improved immediately in response to anti-tuberculosis treatment.
      Serial CSF cultures for M. tuberculosis and the serial single PCRs for M.
      tuberculosis DNA in CSF were all negative during the course of anti-tuberculosis
      treatment. However, serial nested PCR results gradually converted from positive
      to negative, correlating with the improvement in clinical conditions during the
      course of anti-tuberculosis treatment. Therefore, nested PCRs were much more
      useful for the rapid and accurate diagnosis of TBM and for assessment of the
      clinical course and anti-tuberculosis treatment response of TBM than conventional
      CSF cultures and single PCRs. To the best of our knowledge, there have been few
      previous reports of diachronic study in which the serial nested PCR was used to
      test CSF samples obtained earlier in the clinical course of TBM. In conclusion,
      our findings suggest that nested PCR for M. tuberculosis DNA in CSF was highly
      useful not only for rapid and accurate diagnosis of TBM, but also for assessment
      of the antituberculous treatment response in cases highly suspected of TBM
      despite negative results on conventional cultures and single PCRs.

PMID- 15859135
TI  - [Clinical trial of medical device and new GCP].

PMID- 15859134
TI  - [Clinical courses of two male siblings on hemodialysis for Fabry disease ].
AB  - Fabry disease is an X-linked recessive disease resulting from a deficiency of the
      lysosomal hydrolase alpha-galactosidase A. In male patients with the classic
      hemizygous form, acroparesthesias, hypohidrosis, corneal opacities, and
      dysfunction of the heart, brain, and kidney are observed. Recently, it was
      reported that 0.5-1.2% of male chronic hemodialysis (HD) patients were diagnosed
      as having Fabry disease based on the measurement of alpha-galactosidase A
      activity. Fabry disease is thought to be an important cause of end-stage renal
      disease. There are a few reports of patients with Fabry disease on long-term HD.
      Here we report two male siblings with classical type Fabry disease on HD. They
      had acroparesthesias, and hypohidrosis. Their mother had severe heart failure due
      to a heterozygous form of Fabry disease. Case 1 is a 44-year-old male. He had mid
      cerebral apoplexy at 30 years of age. He started maintenance HD in 2000.
      Remarkable left ventricular hypertophy and conduction disorders of the heart were
      found. In 2004, he collapsed and ventricular-tachycardia and severe hypoxic brain
      damage were found. Now his consciousness level has been in the range of 100 to
      300 on the Japan Coma Scale. Case 2 is a 40-year-old male. He started maintenance
      HD in 1993. Malnutrition due to chronic diarrhea and severe ischemic change in
      the brain were found. In 1998, he had severe joint pain of shoulders and fingers
      with ectopic calcifications detected by X ray. The ectopic calcifications were
      extended to the whole body. In 2004, his dementia by ischemic change in the brain
      has rapidly progressed. In conclusion, cardiovascular complications,
      cerebrovascular manifestations, painful ectopic carcifications, and chronic
      diarrheas in our patients were considered to be specific symptoms of Fabry
      disease. Young HD patients with these symptoms will need to be examined for Fabry
      disease.

PMID- 15859137
TI  - [Operative technique aiming at en bloc dissection in esophageal surgery].
AB  - The lymph node metastases of esophageal cancer occur over a wide area. It is
      essential for radical surgery of such metastases to aim at en bloc dissection.
      Otherwise, it can easily become a combination of blunt esophagectomy and lymph
      node sampling through a right thoracotomy. In the intrathoracic procedure, all
      the nodes to be dissected can be harvested while attached to the esophagus
      together with the surrounding connective tissue, except for the pretracheal nodes
      in front of the cardiac branches of the right vagus nerve and the subaortic arch
      nodes. It is important to dissect the left paratracheal nodes en bloc, preserving
      the left recurrent laryngeal nerve. In the abdomen, nodes around the celiac axis
      and nodes on the common hepatic artery and proximal part of the splenic artery
      are all removed en bloc with the perigastric nodes in the left gastric arterial
      basin. The cervical paratracheal and paraesophageal nodes are removed separately
      from the resected esophagus, but the continuity of dissection can be ensured when
      the dissection from the neck meets the empty space made by the dissection along
      the bilateral recurrent laryngeal nerves through the thoracotomy. We believe that
      such en bloc dissection is the key to improving the long-term results of
      esophageal cancer surgery.

PMID- 15859138
TI  - [Lymphatic basin dissection and function-preserving limited gastrectomy for early
      stage gastric carcinoma].
AB  - Sentinel node biopsy accurately predicts the nodal status of early-stage gastric
      carcinomas. Nevertheless, surgeons are concerned about missing a micrometastasis
      in applying the sentinel node-negative finding to surgery. Of 36 patients who
      underwent D2 dissection based on positive sentinel node biopsy, 15 patients had
      histologic metastasis in the sentinel nodes, 20 patients in both the sentinel and
      nonsentinel nodes in the lymphatic basin system, and 1 in the nodes not only in
      the basins but also in the nonbasin system. This means that metastases spread
      along the anatomic lymphatic flows in the early stage. Micrometastases of the
      sentinel nodes develop prior to histologic appearance, and the neighboring
      nonsentinel nodes are also possibly involved in the early stage. This suggests
      that, even in the case of cancer-free sentinel nodes, the basins should be
      dissected. Since 1995, we have performed lymphatic basin dissections and limited
      gastric resections on 159 sentinel node-negative patients. The crude survival
      curve was not different from that of the conventional group. The incidence of
      postoperative distress such as early satiety, unsatisfactory recovery of body
      weight dumping syndrome, duodenogastric reflux, and gallstone formation was
      significantly lower in the limited group than that in the conventional group.

PMID- 15859139
TI  - [Surgical strategy based on the spread mode of gallbladder carcinoma].
AB  - Cancer recurs even from early stage of gallbladder cancer if the bile spills over
      during surgery. The most important point to determine the surgical strategy for
      gallbladder cancer is the spread mode For pT1b gallbladder cancer,
      cholecystectomy in the entire layer and regional lymphadenectomy are necessary.
      Even for pT2 cancer the same surgery is sufficient if the invasion into the
      subserosal layer is minimal. However, anatomic hepatectomy of S4a + 5 and
      extrahepatic bile duct resection combined with D2 + paraaortic lymphadenectomy is
      the fundamental procedure for apparent pT2 or more advanced cancers. If massive
      direct hepatic invasion is present, central hepatectomy or extended right
      hepatectomy is indicated. If the right Glissonian triad is involved, right
      extended hepatectomy is mandatory but the addition of pancreatoduodenectomy must
      be carefully considered to avoid surgical risk. The presence of liver metasis,
      jaundice, apparent paraaortic lymph node metastasis, and involvement of the major
      vessels are not indications for surgery.

PMID- 15859140
TI  - [Hilar cholangiocarcinoma].
AB  - Surgical resection has been reported to be only hope for cure for the patients
      with hilar cholangiocarcinoma. Therefore, first of all, radical surgical
      resection should be considered to be a therapeutic option for hilar
      cholangiocarcinoma as much as possible. In preoperative staging for hilar
      cholangiocarcinoma, various extensive patterns of cancer such as the involvements
      of bile duct, portal vein, hepatic artery and lymph node etc, should be evaluated
      in each patient. As most patients are associated with obstructive jaundice at
      presentation, liver function has to be evaluated by appropriate tests for
      deciding the suitable surgical procedure. When the future remnant liver volume is
      less than 40% or severe liver functional damage exists or greater surgical stress
      is expected, preoperative portal vein embolization might have to be selected. On
      the other hand, if hilar cholangiocarcinoma involves limited region of the hilar
      bile duct confluence, parenchyma preserving hepatectomy such as S1 resection and
      S1 + S4 resection should be selected for avoiding the occurrence of liver
      failure. Combined portal vein resection should be done for the case of the cancer
      involvement of the portal vein without hesitation to improve the prognosis.
      However, hepatic artery resection and reconstruction in the involved case should
      be carefully performed only in severely selected cases. By using several useful
      pre-operative and intra-operative therapeutic modalities, hilar
      cholangiocarcinoma should be surgically resected with curative intent and without
      increasing surgical morbidity and mortality rates.

PMID- 15859141
TI  - [Theories and techniques for resection of the extrapancreatic nerve plexus in the
      head of the pancreas during a Whipple procedure for carcinoma of the pancreas-
      suggestions from the perspective of surgical anatomy and pathology].
AB  - Although various therapeutic modalities for carcinoma of the pancreas are
      available, "curative (R0) resection" is the most important. Thus, the aim of
      surgery for carcinoma of the pancreas is local complete resection of the
      carcinoma. We offer two suggestions for complete resection of carcinoma of the
      pancreas, which shows a strong invasive tendency around nerve fibers, during a
      Whipple procedure. 1. En bloc resection of the right side of nerve plexus of the
      superior mesenteric artery and the first and second nerve plexus of the
      pancreatic head should be performed. It is easy to perform this procedure when
      the superior mesenteric artery should be moved to the right side of the superior
      mesenteric vein through under this vein. 2. The entire cut end of the nerve
      plexus should be investigated during the operation using frozen specimens and
      confirmed to be negative for cancer. If the cut end is positive for cancer,
      additional resection of the nerve plexus should be performed to achieve curative
      resection. The reason is that it is impossible to completely investigate positive
      or negative carcinoma in the cut end of the nerve plexus after surgery, since the
      cut end is long and some specimens are deformed by formalin fixation.

PMID- 15859142
TI  - [Selection and techniques of surgical procedures based on the mode of cancer
      spread of rectal cancer].
AB  - The author reviewed recent results of Japanese and international studies on
      preoperative staging, pathology of bisopied specimens, sentinel node navigation
      surgery, and single tumor cells in rectal cancer. Preoperative staging with high
      accuracy is possible using high spatial MRI imaging. Examination of
      circumferential resection margins is incompatible with that of lymph nodes
      Intersphincteric resection can be an alternative to abdominoperineal resection
      for selected rectal tumors located at the anorectal junction without compromising
      the chance for cure. Although information on sentinel node navigation surgery and
      isolated single cells has accumulated, the selection of surgical procedures
      should not be based on these investigations. We emphasize that multiinstitutional
      clinical trials of adjuvant chemoradiotherapy and surgical treatment are
      indispensable for developing treatments for rectal cancer in Japan.

PMID- 15859144
TI  - [The advantage of video-assisted thoracic surgery in general thoracic surgery].

PMID- 15859145
TI  - [Controversies of video-assisted thoracic surgery (VATS)].

PMID- 15859146
TI  - [What we can learn from a case of medical malpractice].

PMID- 15859147
TI  - [Laser photocoagulation: today and beyond].

PMID- 15859148
TI  - [A review of the molecular mechanism of development of Leber hereditary optic
      neuropathy].
AB  - BACKGROUND: Leber hereditary optic neuropathy (LHON) is a maternally transmitted,
      bilateral optic neuropathy. Although mitochondrial (mt) DNA mutations are known
      to be associated with the maternal inheritance, there are few reviews on how they
      lead to optic neuropathy. In addition, low penetrance and male preponderance
      cannot be accounted for by mtDNA mutations alone. METHODS: Presumable molecular
      mechanisms of LHON due to mtDNA mutations were reviewed based on cellular and
      molecular studies. Environmental factors regulating LHON expression were also
      extracted from pedigree analyses. RESULT: Histopathologically, LHON, comprises
      apoptosis of retinal ganglion cells and chronic inflammation of the retrobulbar
      optic nerve. Trans-mitochondrial cybrid studies demonstrated that mtDNA mutations
      cause an increase in the production of reactive oxygen species. Over the last 50
      years, the penetrance in females has been greatly reduced in both Japanese and
      Caucasian pedigrees. Smoking, over-consumption of alcohol, and sex hormones may
      control LHON expression. CONCLUSIONS: These findings indicate that LHON is not a
      monogenetic disease, but that LHON transmits a predisposition to develop optic
      neuropathy and requires additional factors triggering phenotypic expression.
      Therapeutic intervention including gene therapy should be further investigated.

PMID- 15859149
TI  - [Experimental cataract models produced by repeated blunt mechanical stimulation
      and elucidation of the pathogenetic mechanism].
AB  - PURPOSE: The pathogenesis of cataract produced by mechanical stimulation of the
      eye was studied using experimental models. METHODS: The eyes of rabbits (in vivo)
      and the extracted lenses of rats (in vitro) were subjected to vibration from an
      electric massage machine and tapping. The histological changes, aqueous flare
      score, protein and prostaglandin (PG) E2 levels in aqueous humor, and the rate of
      vitreous liquefaction were measured, and the involvement of apoptosis was
      examined in the rabbit model. RESULTS: In both models, mechanical stimulation
      resulted in a high frequency of opacification of the lens in the anterior or
      posterior subcapsular region. In the in vivo model, histopathological examination
      revealed vacuolar changes in the lens epithelium and swelling of lens fibers.
      Increases in aqueous flare score, protein level, PGE2 level, and the rate of
      vitreous liquefaction were confirmed. The involvement of apoptosis was not
      proven. CONCLUSION: Repeated mechanical stimulation of the eye produced lens
      opacification. In patients with atopic dermatitis, mechanical stimulation such as
      a habit of eye tapping may be the cause of or a factor in promoting cataract
      development.

PMID- 15859150
TI  - [Clinical evaluation of primary position upbeat nystagmus].
AB  - BACKGROUND: Primary position upbeat nystagmus is a vertical nystagmus presenting
      in the primary position. However, cases of primary position upbeat nystagmus have
      rarely been reported. SUBJECTS: We evaluated the locations of lesions and
      pathogenesis in 11 patients with primary position upbeat nystagmus. The lesions
      were located mostly in the median portion of the cerebellum and medulla
      oblongata. In 7 out of 11 patients, intracranial lesions were identified by
      computed tomography and magnetic resonance imaging. They were located in the
      median portion of the cerebellum and medulla oblongata except for one adult
      patient with astrocytoma. The etiologies were 4 tumors, 3 intracranial vascular
      disorders, 2 Wernicke encephalopathies, 1 congenital anomaly, and 1 inflammation.
      CONCLUSION: The lesions were located mostly in the median portion of the
      cerebellum and medulla oblongata, and especially in the cerebellum in children.
      The main etiologies were tumors in children and vascular disorders and Wernicke
      encephalopathy in adults.

PMID- 15859151
TI  - [Visual prognosis and prognostic risk factors after photocoagulation for diffuse
      diabetic macular edema].
AB  - PURPOSE: To investigate the efficacy of photocoagulation for diffuse diabetic
      macular edema. SUBJECTS AND METHODS: One hundred and fifty eyes with diffuse
      diabetic macular edema were treated by laser photocoagulation (grid pattern
      photocoagulation, in some instances combined with direct photocoagulation) and
      followed up more than 1 year. The visual prognosis of these cases was
      retrospectively studied. RESULTS: The logarithm of the minimum angle of
      resolution (Log MAR) final visual acuity after photocoagulation was improved more
      than 0.2 levels in 62 eyes (41%) of a total 150 eyes, and in 60% of 87 eyes in
      which preoperative visual acuity had been less than 0.5. Average visual acuity
      after photocoagulation reached a plateau within three months after surgery, and
      84% of the eyes with 0.5 or better preoperative visual acuity achieved 0.5 or
      better final visual acuity. There was correlation between visual prognosis and
      the following preoperative factors: preoperative visual acuity, hard exudates,
      fluorescein leakage, grid area, hyperlipidemia, and renal failure. CONCLUSIONS:
      Grid photocoagulation as a treatment for diffuse diabetic macular edema is
      effective to improve or maintain visual acuity. Alternative treatment such as
      vitrectomy should be considered after three-month observation on the outcome of
      grid photocoagulation.

PMID- 15859153
TI  - [A review 22. Rhegmatogenous retinal detachment].

PMID- 15859152
TI  - [Low power transpupillary thermotherapy of choroidal neovascularization].
AB  - PURPOSE: To assess the effectiveness of low power transpupillary thermotherapy
      (TTT) for choroidal neovascularization (CNV). METHOD: We performed TTT on 55 eyes
      of 55 patients with subretinal CNV between April 2001 and December 2002, and
      observed them after therapy for more than 6 months. The laser power ranged from
      80 to 320 mW when the spot size was 3 mm. We evaluated visual acuity, subretinal
      fluid (SRF), and CNV size. RESULTS: Visual acuity improved by 2 lines or more in
      16 eyes (29%), was unchanged in 19 eyes (35%), and decreased in 20 eyes (36%).
      SRF decreased in 30 eyes (54%), was unchanged in 13 eyes (24%), and increased in
      12 eyes (22%). CNV diminished in 33 eyes (60%), was unchanged in 10 eyes (18%),
      and became enlarged in 12 eyes (22%). CONCLUSIONS: Low power TTT can be an
      effective treatment for subgroups of patients with subfoveal CNV.

PMID- 15859154
TI  - Chondrosarcoma of the urinary bladder and establishment of a human chondrosarcoma
      cell line (OCUU-6).
AB  - Chondrosarcoma is a very rare tumor of the urinary bladder, with only 4 cases
      reported to date. In this study, we report on a case of a 73-year-old male who
      presented bladder mass and right hydroureteronephrosis. Radical cystectomy, right
      nephrectomy and left ureterocutaneoustomy were performed, and histological study
      disclosed chondrosarcoma of the urinary bladder. As reported in other cases, the
      tumor was highly aggressive with a short clinical course, and the patient died of
      carcinomatous pleuritis at one month after surgery. Subsequently, we successfully
      established a human chondrosarcoma cell line (OCUU-6) from the pleural effusion
      of the patient.

PMID- 15859156
TI  - Biological characteristics of cultured cells derived from various types of human
      brain tumors.
AB  - We placed in culture brain tumors from 45 cases (7 cases of astrocytoma, 2 from
      oligodendrogliomas, 2 glioblastomas, 2 ependymomas, 13 meningiomas, 6 pituitary
      adenomas, 5 neurinomas, a malignant lymphoma, a choroid plexus papilloma, and 6
      metastatic tumors) and succeeded in making a primary culture from 33, and
      maintained 17 in vitro over a considerable period of time (greater than three
      months). In the early period of the primary cultures, the astrocytoma cells had
      cytoplasmic processes which contacted each other, the oligodendroglioma cells
      were small and spindle-shaped, the glioblastoma cells were neoplastic with
      pleopmorphic features and possessed cytoplasmic processes, the ependymoma cells
      formed a rosette-like cell arrangement, the meningioma cells were spindle- or
      round-shaped cells and characterized as forming psammoma bodies, the pituitary
      adenoma cells were round- or oval-shaped cells and produced growth hormone (GH),
      adenocorticoid tropic hormone (ACTH), prolactin, or other hypophyseal hormones,
      the choroid plexus papilloma cells were round-or polygonal and showed a papillary
      cell arrangement, the neurinoma cells were spindle- or fibrous-shaped cells, and
      the malignant lymphoma cells were round and formed cell aggregates floating in
      the culture medium.

PMID- 15859155
TI  - Animal embryonic stem (ES) cells: self-renewal, pluripotency, transgenesis and
      nuclear transfer.
AB  - Mouse embryonic stem (ES) cells can be maintained indefinitely in the presence of
      leukemia inhibitory factor (LIF) and they express markers of self-renewal and
      pluripotency, which include the transcription factor Oct 4, STAT-3, stage
      specific embryonic antigen (SSEA)-1, and alkaline phosphatase (AP). Upon removal
      of LIF, from the culture medium they cease to express markers such as Oct 4,
      rapidly losing the capacity for self-renewal and differentiating into a variety
      of cell types. Gene targeting is feasible in murine ES cells because these cells
      can be maintained in an undifferentiated state long enough to allow selection of
      properly targeted cell colonies with a high frequency of homologous
      recombination. Furthermore, blastocysts cloned from cultured murine ES cells
      develop to term at an efficiency (10-30%) that is three to ten times higher than
      blastocysts cloned from the nuclei of differentiated somatic cells. It seems
      likely that ES cells require less extensive reprogramming than do somatic cells,
      perhaps because in ES cells, many genes that are essential for early development
      are already active and thus do not require reactivation. Recently, we succeeded
      in isolating immortalized equine and bovine ES cells with a normal karyotype,
      that exhibit features similar to those of murine ES cells and express Oct 4, STAT
      3, SSEA-1 and AP. We further confirmed the pluripotential ability of these cells,
      which were able to undergo somatic differentiation in vitro to neural progenitors
      and to endothelial or hematopoietic lineages. We were able to use bovine ES
      cells, as a source of nuclei for nuclear transfer (NT) and we generated cloned
      cattle with a higher frequency of pregnancies to term than has been achieved with
      differentiated somatic cells. Moreover, bovine ES cells that expressed enhanced
      green fluorescent protein (EGFP) were incorporated into both the inner cell mass
      (ICM) and the trophectdermal cells of developing blastocysts. These findings
      should facilitate targeted genetic manipulation of the genome and should allow
      production of cloned cattle in a single step after modification, as appropriate,
      of the genome.

PMID- 15859157
TI  - Establishment and characterization of a pluripotent stem cell line derived from
      human amniotic membranes and initiation of germ layers in vitro.
AB  - OBJECTIVES: Pluripotent stem cells are proposed to be used in regenerative
      therapy and may exist in the human amniotic membrane. The present article is
      aimed at establishing a pluripotent stem cell line from human placenta. METHODS:
      HAM-1 (stem cell line derived from human amniotic membranes) was established by
      the colonial cloning technique using aMEM culture medium containing 10 ng/ml of
      EGF, 10 ng/ml of hLIF and 10% fetal bovine serum. RESULTS: HAM-1 cells appeared
      to maintain a normal karyotype indefinitely in vitro and expressed markers
      characteristic of stem cells from mice and human, namely alkaline phosphatase.
      Also, these cells contributed to the formation of chimeric mouse embryoid bodies
      and gave rise to cells of all germ layers in vitro. CONCLUSIONS: This study
      demonstrates that human amniotic membranes derived stem cells have a wide
      developmental capability and might be utilized to regenerate different types of
      cells or tissues for transplantation therapy.

PMID- 15859158
TI  - Histogenesis of carcinosarcoma and establishment of leiomyosarcoma cell line
      (HTMMT) derived from human uterine carcinosarcoma.
AB  - A cell line designated HTMMT was established from the human uterine
      carcinosarcoma (composed of leiomyosarcoma and adenocarcinoma) of a 66-year-old
      Japanese woman. The cell line grew well and 83 serial passages were successively
      done within 24 months. The cell line contained spindle- or fibrous-shaped cells
      that revealed neoplastic and pleomorphic features, and multipled rapidly without
      contact inhibition. These cells were characterized as possessing myofibrils. The
      karyotype exhibited hyperploidy and the chromosome number was ranged from 87 to
      100. The cells were transplanted into an immune-depressed hamster cheek pouch or
      into nude mouse skin, but produced no tumors. We supported the combination theory
      for the histogenesis of the carcinosarcoma.

PMID- 15859159
TI  - Establishment and characterization of JHUCS-1 cell line derived from
      carcinosarcoma of the human uterus.
AB  - The cell line designed JHUCS-1 was established from a carcinosarcoma (malignant
      mixed mesodermal tumor) of the uterus that was surgically removed from a 57-year
      old Japanese woman. We carefully examined the histopathology of the original
      tumor after the cell line was established and noted differentiation into a
      neuroendocrine carcinoma within the tumor's epithelial components.
      Immunohistochemical staining of the tumorous tissue that had been
      heterotransplanted was positive for Leu7. Additionally, secretary granules were
      observed in the grafted cells as determined by electron microscopy. These results
      support the existence of neuroendocrine cells within the JHUCS-1 cell line.

PMID- 15859160
TI  - Establishment and characterization of a new human glioblastoma cell line, NYGM.
AB  - A cell line designated NYGM was established from a human cerebral glioblastoma
      multiforme (GBM) obtained from a 75-year-old Japanese woman. The cell line has
      grown slowly without interruption and has been propagated continuously by serial
      passages (more than 80 passage) during the past 3 years. The cultured cells were
      fusiform or polyhedral in shape. The population doubling time was 24 hours. The
      chromosomal number varied between 77 and 88, with modal chromosomal number of 84.
      NYGM cells concomitantly expressed MET receptor tyrosine kinase (a product of c
      met protooncogene) and its ligand HGF/SF (hepatocyte growth factor/scatter
      factor), as well as HGF activator and HGF activator inhibitors. The cells might
      be useful for the study of pericellular regulation of HGF/SF-MET signaling and
      HGF activation of GBM cells.

PMID- 15859161
TI  - Establishment and characterization of human uterine cervical epidermoid carcinoma
      cell line HHUS containing HPV 59 DNA.
AB  - The cell line designated HHUS was established from human uterine cervical
      keratinizing squamous cell carcinoma. The HHUS cell line was subcultivated more
      than 70 times within 3 years. The cultured cells, polygonal or spindle, with
      neoplastic and pleomorphic features, appeared epithelial in shape, with a
      pavement-like arrangement and grew in multi-layers without contact inhibition.
      The chromosome number was varied from 40 to 88, and the modal number was stable
      in diploid range. The cultured cells produced keratinizing squamous cell
      carcinomas by heterotransplantation into the subcutis of nude mice. The HHUS
      cells were characterized as producing large amounts of SCC, in vitro and
      possessing HPV-59 DNA genomes.

PMID- 15859162
TI  - Unexpected gifts.

PMID- 15859163
TI  - Challenges to providing care to a fearful and angry patient and family.

PMID- 15859164
TI  - Planning and organizing a multidisciplinary psychosocial oncology service.
AB  - Providing psychosocial care to patients with cancer and their families is a
      formidable task given the current fiscal environment in hospitals. As the pool of
      available resources shrinks and populations shift from inpatient to outpatient,
      psychosocial staff are challenged to find creative, versatile, and efficient ways
      to deliver quality services and programs. This article describes the efforts to
      plan and implement psychosocial care at a cancer center facing the constraints of
      limited staff and decreasing resources. The background of the project, the
      development and implementation of a strategic plan, and a 1-year evaluation of
      the attainment of the objectives in the plan are described. The success of this
      approach and implications for psychosocial staff at other institutions are
      discussed.

PMID- 15859165
TI  - Do people with cancer postpone death to celebrate special occasions?
AB  - Several researchers have claimed that a connection exists between deathdays and
      birthdays or other special occasions. Some people, especially women, appear to
      postpone death until after their birthdays or other special occasions to
      celebrate these events one more time. The purpose of this retrospective study was
      to determine if a deathday-birthday or deathday-Christmas connection was evident
      in cancer-related deaths. Data were obtained from the Rochester (New York)
      Regional Tumor Registry (N = 2566), the New York State Cancer Registry (N =
      50,562), and the Ohio State Department of Health (N = 73,907) for three samples
      of individuals who died from cancer. Only a few deathday-birthday connections
      were evident. However, these connections were not replicated across states and
      years.

PMID- 15859166
TI  - Interferon-alpha: a clinical update.
AB  - The use of interferon-alpha (IFN-alpha) for the treatment of cancer has continued
      to expand since the initiation of clinical trials in the early 1980s. Regulatory
      approval of IFN-alpha was first granted in 1986, and many investigational trials
      continue. Expanded approvals are anticipated during the next few years as the
      clinical benefits of IFN-alpha are further delineated. Many in the field of
      oncology care for patients who are receiving IFN-alpha therapy. Management of
      these patients offers a challenge; providing comprehensive care in diverse areas,
      particularly patient support and the management of side effects. Reassurance that
      many of the side effects associated with IFN-alpha therapy will diminish as
      treatment continues and that others can be managed assists patients in continuing
      therapy. Educating patients about the disease and treatment can reduce their
      anxieties and increase their level of comfort with therapy. Actions taken by the
      healthcare team toward side effect intervention, patient advocacy, social support
      and patient education and motivation can allow patients to stay the course of IFN
      alpha therapy and achieve a therapeutic response.

PMID- 15859167
TI  - Community prostate cancer screening.
AB  - Health promotion and cancer prevention, including screening, are two important
      aspects of cancer care. However barriers exist to patients receiving recommended
      cancer screening procedures. One way to overcome these barriers is through the
      use of community cancer screening programs. This article presents a prototype of
      a community prostate cancer screening program. The program planning, staffing,
      promotion, cost and finance, and follow-up activities are explained. Furthermore,
      examples of communication tools and follow-up protocol, and results of 4 years of
      community screening programs are described. Recommendations for future community
      screening give insight for program improvement.

PMID- 15859169
TI  - Cancer resource center: a setting for patient empowerment.

PMID- 15859168
TI  - Psychosocial concerns associated with recurrent cancer.
AB  - Little research has been directed toward the needs of those with recurrent
      cancer. The purpose of this descriptive study was to describe the psychosocial
      problems and concerns associated with recurrence. Purposeful sampling for persons
      with recent recurrent malignancy produced a sample (N = 20) with diverse medical
      and demographic characteristics. Subjects completed the Psychosocial Adjustment
      to Illness Scale and an audiotaped structured interview to discuss the responses
      on the Psychosocial Adjustment to illness Scale in depth. Specific areas explored
      in the interviews included health-related issues, work and financial concerns,
      family and marital relationships, relationships with friends, and psychological
      distress. Verbatim transcripts were analyzed for themes and trends and double
      coded with 94% Inter-rater agreement. Psychosocial Adjustment to Illness Scale
      scores were high, suggesting that this group has many psychosocial needs.
      Implications for health professionals include a need for thorough psychosocial
      assessment and improved communication with these patients.

PMID- 15859170
TI  - Resources for Asian Pacific Islanders.

PMID- 15859171
TI  - Cancer registrars: expanding the multidisciplinary team.

PMID- 15859172
TI  - Eighty years of the National Institute of Public Health in Prague.

PMID- 15859173
TI  - Hygiene as an academic discipline at Austrian universities: a survey on the
      occasion of the 120th anniversary of the Institute of Hygiene in Graz.

PMID- 15859174
TI  - Cadmium exposure pathways in the Czech urban population.
AB  - The article describes the exposure pathways of cadmium in the Czech urban
      population. The data on Cd concentrations originated from the Environmental
      Health Monitoring System, which has been realized in 30 cities since 1994. The
      data on cadmium content in particular exposure pathways - diet, drinking water,
      ambient air and soil -were processed for the period 1994-2003. The estimate of
      the daily dietary intake for an average adult population amounted to 11-19
      microg/d, i.e. 0.17-0.30 microg/kg bw/d, which represents 17%-30% of the PTWI
      (provisional tolerable weekly intake). The contribution from drinking water to
      the oral exposure is low; on average 0.5 microg/d. Potential exposure to airborne
      Cd was estimated at about 0.02 microg/d. The additional Cd intake from urban soil
      ingestion probable in small children was found to be insignificant based on Cd
      concentrations in the soil of kindergarten playgrounds. Biomonitoring outputs
      characterize the recent and life-long cadmium burden of the Czech population from
      general environment In 1994-2003, the median blood Cd levels ranged in the
      interval 0.9-0.4 microg/l blood, in smokers being more than double that in non
      smokers. Blood Cd levels detected indicate slightly decreasing trend as well as
      urine Cd levels (range of median values 0.44-0.28 microg/g creatinine). Since
      1996 the levels in children have been found in more than 50% cases below the
      detection limit of the methods used. The estimated total cadmium intake in the
      Czech urban population does not signalize any increased risk of health impairment
      considering non-carcinogenic effects.

PMID- 15859175
TI  - Safety and immunogenicity of a combined vaccine against hepatitis A and B in
      patients with autoimmune hepatitis.
AB  - Patients with autoimmune hepatitis (AIH) are a group at risk of disease
      exacerbation or relapse of the underlying disease should they fall ill with
      infectious hepatitis A (HAV) or B (HBV). Therefore, it seems appropriate to
      protect this group of persons against HAV and HBV disease by vaccination. An open
      study evaluated the safety, reactogenicity and immunogenicity of a combined HAV
      and HBV vaccine in 10 patients with AIH (6 patients aged 1-15 years and four
      patients aged 16+ years). The vaccine was administered using a three-dose
      vaccination schedule (0, 1 and 6 months). The vaccine course was well tolerated,
      safe and did not aggravate the clinical course of the underlying disease.
      Patients responded with 100% seroconversion for antibody to the HAV vaccine
      component and geometric mean antibody concentration (GIVIC) comparable to healthy
      cohorts. Response to the HBV component antigen was comparable to previous reports
      of HBV vaccination in immune compromised individuals with lower GMC than observed
      in healthy populations. One month after the third vaccine dose (month 7), all six
      vaccinees in the 1-15 years age group developed protective levels of anti-HBs as
      compared to two of the four vaccinees in the 16+ years age group.

PMID- 15859176
TI  - Altitudinal distribution limit of the tick Ixodes ricinus shifted considerably
      towards higher altitudes in central Europe: results of three years monitoring in
      the Krkonose Mts. (Czech Republic).
AB  - The aim of the study was to monitor present status of the Ixodes ricinus tick
      vertical distribution in the Krkonose Mts. (Czech Republic) and evaluate its
      potential changes. Two methods were used: monitoring of tick presence on dogs in
      2001-2002 and direct monitoring of host-seeking ticks by flagging on two vertical
      transects reaching from 620 to 1270 m above sea level (a. s. l.) and from 600 to
      1020 m in 2002-2003. Moreover ticks were monitored by flagging at another 13
      localities situated in 800-1299 m a. s. l. in 2003. Both monitoring methods
      revealed an obvious shift in altitudinal distribution limit of the tick I.
      ricinus in the Krkonose Mts. They both showed that ticks recently penetrate even
      up to a timberline (approximately 1250 m a. s. l.). The number of recorded host
      seeking ticks rapidly decreased with increasing altitude. Whereas the average
      number of recorded nymphs converted per 60 minutes of flagging reached 15.2-25.7
      nymphs in 700-799 m a. s. l. and 3.3-23.3 in 800-899 m, it was 4-9.6 nymphs in
      900-999 m, 1.5-1.7 nymphs in 1000-1099 m and only 0.2 nymph in 1100-1299 m a. s.
      l. The observed shift of the tick altitudinal distribution limit at the same time
      results in extension of areas with potential risk of tick-borne diseases.

PMID- 15859177
TI  - Outbreaks of epidemic kerato-conjunctivitis in two hospital wards.
AB  - The authors analyzed two hospital outbreaks of epidemic keratoconjunctivitis
      (EKC), one at the Department of Ophthalmology (30 cases) and another one at the
      Department of Premature Newborns (22 cases). In both outbreaks, EKC was diagnosed
      in inpatients (16 and 6 respectively), outpatients (5 and 3 respectively),
      healthcare workers (HCWs) (3 and 5 respectively), and relatives of EKC patients
      (6 and 8 respectively). Implemented infection control measures included isolation
      precautions, improved disinfection and hand-washing of both hospital and
      outpatient department personnel. Shortly after implementation of control measures
      the rate of infection transmission started to decrease significantly.

PMID- 15859178
TI  - The association of Candida infection with intrauterine contraceptive device.
AB  - In order to analyse the relationship between intrauterine contraceptive device
      (IUCD) usage and Candida infection, we planned to examine cytologically the
      cervico-vaginal smears of 600 patients stained with Papanicolou method. Among 56
      IUCD users 8 women had Candida infection (14%) while 44 of 544 non-users (8%)
      were infected by this fungus. Our detailed analyses indicated that the prolonged
      usage of Cu-IUCD may predispose the cervico-vaginal flora for Candida especially
      for the infectious "hyphae" form although statistically the correlation between
      IUCD usage and candidiasis was not significant (p>0.05). These findings imply the
      importance of controlled IUCD usage against Candida infection and its removal for
      treatment if necessary. Because retained IUCD may cause serious clinical
      complications especially in pregnant women such as "fetal candidiasis" which may
      lead to miscarriage, premature labor or ectopic pregnancy. For these reasons, the
      possibility of candidiasis should be considered in patients wearing IUCD for a
      long period.

PMID- 15859179
TI  - Long-term hospital treatment for patients with chronic obstructive pulmonary
      disease.
AB  - The aim of this study is to describe the long-term hospital treatment provided
      for chronic obstructive pulmonary disease (COPD) patients in Finland in 1972-2001
      and changes over that period. Data on all treatment periods for persons aged over
      45 years with a primary or secondary diagnosis of COPD (International
      Classification of Diseases - ICD 8: 491 and 492, ICD 9: 491, 492 and 496, ICD 10:
      J41-J44) beginning in the years 1972-2001 were gathered from the treatment
      register of the Finnish National Research and Development Centre for Welfare and
      Health and examined particularly with respect to long treatment periods (over 90
      days). A total of 10,176 long treatment periods were recorded as having begun
      during the years in question. The number of treatment periods for men dropped by
      65.8% over the time interval 1972-2001, while that for women increased by 4.7%.
      The number of treatment periods in university and central hospitals dropped by
      97.6%. The total number of hospitalization days in the long treatment periods
      over the years 1972-2001 was 3,844,521, the men accounting for 82.9% in 1972-1976
      and 67.3% in 1997-2001. The number of days required by men dropped by 82.1% and
      that for women by 57.8%. The number of days in university and central hospitals
      decreased by 98.4%, and that in health centre hospitals by 47.6%. COPD is a cause
      of repeated hospitalization, but it less and less often leads to long-term
      hospital treatment nowadays. The number of treatment days required for men has
      fallen more rapidly than that for women, and both the lengths and numbers of
      treatment periods have decreased at all levels of hospital, although with a
      tendency for treatment to be concentrated nowadays in the health centre
      hospitals. Long-term treatment for COPD has virtually disappeared from the sphere
      of specialized health care. The trends observed here are attributable to marked
      changes in the structure of the health service, with more accent being placed on
      open care, and a decrease in the numbers of male smokers.

PMID- 15859180
TI  - Fight childhood obesity to help prevent diabetes, say WHO & IDF.

PMID- 15859181
TI  - The effectiveness of a body mass reduction program in obese women in
      perimenopausal and menopausal age compared with the effectiveness of such a
      program in younger (18-44 years of age) women living in Poland.
AB  - OBJECTIVE: The aim of the work was: to compare the effectiveness of body mass
      reducing program in women of perimenopausal (and menopausal) age with the
      effectiveness of such a program when it was applied to women aged 18-44 years.
      METHODS: The paper deals with observation study of the group of obese patients
      recruited and treated in Bialystok's Clinical Center for Cardiology and Body Mass
      Reduction. The authors summarize 12 months of clinical observation (as it was
      initially planned) of the two groups of obese women, taking part in the special
      body mass reduction program; Group I - 81 women in perimenopausal and menopausal
      age, Group II - 107 women in 18-44 years of age. The proposed treatment contained
      diet, physical exercises, psychological support and pharmacotherapy. RESULTS: The
      positive reaction for the treatment of obesity was less visible in obese women in
      perimenopausal and menopausal age, than in the group of obese women in 18-44
      years of age (change of BMI in the group of younger women was -3.44 kg/m2 vs. 
      2.65 kg/m2 in older women). As it was observed, the weaker reaction for the
      proposed treatment in the group of older women, was not related to lower BMR,
      than in the group of younger obese women. Provisional result shows that use of
      HRT (Hormonal Replace Therapy) may probably result in better response of body
      mass reduction in perimenopausal and menopausal women. CONCLUSION: The high
      dropout of the patients included into the study does not allow to formulate
      unequivocal conclusions but it seems that body mass reduction program for women
      in perimenopausal and menopausal age should concentrate on building the
      motivation of the patients, HRT may play some role in improvement of
      effectiveness of such program but this should be confirmed by further studies.

PMID- 15859182
TI  - The excretion rates of stress hormones under mental work.
AB  - The aim of the study was to assess stress on the basis of the excretion rates of
      stress hormones in occupational groups under mental stress. The investigation
      includes 293 persons, working in power engineering, education, public health and
      information sector. The stress hormones adrenaline, noradrenaline and 11
      oxycorticosteroids (11-OCS) were followed during the working day using
      spectrofluorimetric methods. Very high excretion rates of adrenaline,
      noradrenaline and/or 11-OCS were found with leading radio editors, responsible
      engineers and operators in nuclear power station (NPS), teachers in secondary
      schools, designing engineers. In conclusion our data indicate high stress in
      occupational groups working under high psychological demands, high
      responsibility, making important managing decisions, low job control and are
      discussed with regard to the health risk.

PMID- 15859183
TI  - Environmental and occupational epidemiology in Italy.

PMID- 15859184
TI  - A history of union struggles for control of the work environment in Italy.
AB  - The article describes, from a diachronic perspective, the struggle to enhance
      workers' health conditions in Italy throughout the twentieth century. The authors
      adopt the workers' viewpoint, highlighting the relevance of trade unions' so
      called "participatory model," and sketching the recent impact of European
      legislation on the country's laws.

PMID- 15859185
TI  - The first century of the "clinica del lavoro" in Milan.
AB  - The Clinica del Lavoro was created in Milan at the beginning of the 20th century
      by Luigi Devotto, who deemed it essential for physicians and health researchers
      to get involved in the life and health problems of working populations. The main
      roles of the Clinica del Lavoro were to educate medical students and train
      physicians; study actual workplaces, examine health and safety hazards and their
      noxious effects; and create initiatives and services to protect and promote
      workers' health. Important scientific contributions were made in several fields,
      including chemical carcinogenesis, effects of mineral and biologicalfibers,
      mechanism of action of silica dust, methods for the detection and measurements of
      toxic substances in both the work environment and workers' biological media.

PMID- 15859186
TI  - National Institute for Occupational Safety and Prevention (ISPESL): role in
      occupational health and safety.
AB  - The article explains the role of the Italian National Institute for Occupational
      Safety and Prevention (ISPESL), a public research body dealing with occupational
      and environmental health. Its organization, institutional roles, activities,
      facilities, and resources are outlined. Especially important is ISPESL's
      participation in national and international occupational safety and health
      networks. The Institute is active in epidemiologic surveillance of workers
      exposed to physical, chemical, and biological hazards.

PMID- 15859187
TI  - Population attributable risk for occupational cancer in Italy.
AB  - Population studies estimating the proportion of cancer attributable to occupation
      (PAR) in different geographical areas in Italy are reviewed. Studies using lists
      of industrial activities and occupations which are known or suspected to entail
      exposure to lung carcinogens gave lung cancer PARs between 5% and 36%. Those
      using job-exposure matrices estimated PARs of 3%-53%, with most of the values
      ranging between 17 and 33%. For bladder cancer, PARs ranged between 4% and 24%.
      The uses and limitations of calculating population attribultable risk are
      discussed.

PMID- 15859188
TI  - The occupational health and safety services of the national health system in
      Italy.
AB  - Working conditions have been addressed by laws in Italy since the 1950s, but the
      revision of the penal sanction laws in 1994 gave greater responsibility to those
      who had for many years been the de facto "police" of occupational health and
      safety services, allowing them to carry out inspections and to formulate rules
      for safety. Current preventive services for OHS within the Italian National
      Health Service are described, and their main features and developments and
      perspectives for the near future are situated in relation to EU legislation.
      There is a growing dichotomy in services between Northern and Southern Italy. The
      shift towards deregulation and decentralization of the current Government
      jeopardizes the prevention system. An efficient service will require a strong
      information system based on reliable notification; communication, training and
      assistance; and control and surveillance.

PMID- 15859189
TI  - Asbestos-related diseases in Italy: epidemiologic evidences and public health
      issues.
AB  - Epidemiologic information about asbestos-related diseases in Italy, derived from
      mortality data, epidemiologic surveillance, and analytical studies, is presented.
      These systems evidence exposures to asbestos and relative risks for populations
      exposed in work environments and also in the general environment, and provide
      objective data to identify sources of exposure and for risk management.
      Limitations and perspectives of Italian studies are considered, and public health
      issues evaluated: the risk for migrants, social security aspects, and asbestos
      related disease in the courts. Although asbestos use was banned in 1992,
      information and risk communication efforts should be implemented to empower
      affected individuals and communities and to pursue equitable allocation of
      resources for primary prevention and health surveillance.

PMID- 15859190
TI  - Evaluation of work-related diseases by the Italian Institute of Insurance for
      Professional Illness and Injuries (INAIL).
AB  - Based on a predetermined list of job-related diseases, INAIL makes compensation
      decisions in cases of work-related diseases in Italy. Its functioning is somewhat
      hampered by imprecision in the disease classification and infrequency of updating
      the list, as well as rapid turnover of workers in some categories of jobs.

PMID- 15859191
TI  - Epidemiology in the Italian courts: the experience of a magistrate.
AB  - The role of epidemiology in judgments of Italian courts relative to criminal
      liability for work-related injuries is described. Specific court decisions and
      the reasoning behind them are presented.

PMID- 15859192
TI  - Occupational exposures to carcinogens in Italy: an update of CAREX database.
AB  - To update estimates of the prevalence of occupational exposures to carcinogens in
      Italy, the 85 CAREX agents were re-assessed. The original exposure estimates in
      the CAREX database were updated, taking into account changes in exposure patterns
      and in numbers of employees by industrial class. The 21.8 million employees in
      Italy, 19.4 in industry and services, 2.4 in agriculture, had 4.2 million
      exposures. Prevalences of exposures were highest for environmental (passive)
      tobacco smoke (800,000 exposures), solar radiation (700,000), diesel engine
      exhaust (500,000), wood dust (280,000), silica (250,000), lead and inorganic lead
      compounds (230,000), benzene (180 000), hexavalent chromium compounds (160,000),
      glass wool (140,000), and PAHs (120,000). Exposures to carcinogens at work are
      still an issue in Italy and do not appear to be controlled as strictly as they
      should be.

PMID- 15859193
TI  - The health of foreign workers in Italy.
AB  - At the beginning of 2002, there were 1,600,000 foreign-born persons living in
      Italy; the majority from countries outside Europe. Those residing in the country
      for working purposes were 800,680. Italy's shift to a tertiary and service
      oriented economy has considerably modified the working market, concentrating
      demand at two extremes: on one hand, a highly specialized workforce, and on the
      other, a totally unqualified, mobile, and flexible one, which includes most
      immigrants.

PMID- 15859194
TI  - Factors other than risks in the workplace as determinants of socioeconomic
      differences in health in Italy.
AB  - To evaluate differences in mortality by social class and to determine the impacts
      of socioeconomic factors on health inequalities in Italy, mortality data from
      1981-2001 were analyzed as a function of social class in Turin, controlling for
      occupational risks, housing conditions, and education. For general and cause
      specific mortality, the weight of each socioeconomic indicator was evaluated on
      population-attributable fraction to social class. Among men, mortality risk was
      significantly higher in unskilled blue-collar workers (RR = 1.45). Among women,
      the differences by social class were slighter. Education and economic status
      mostly explain the mortality differences by social class in men, while economic
      status showed the highest contribution in women.

PMID- 15859195
TI  - Occupational injuries in Italy.
AB  - Data collected by the Italian Funds for Occupational Injuries and Diseases
      (INAIL) on incidence and mortality for occupational injuries in Italy during 1951
      2001 are described with respect to the two main occupational sectors, Industry
      and Services, and Agriculture. Comparisons with other EU countries are included
      to place the current severe phenomenon in context. An ad hoc analysis aimed at
      verifying the completeness of the data on occupational fatal accidents collected
      by INAIL in Tuscany is reported: a linkage between the INAIL data and those
      registered by the Tuscan Regional Mortality Registry highlights that a number of
      working areas are not covered by INAIL, a problem whose solution would be useful
      for primary prevention.

PMID- 15859196
TI  - Late industrial development and occupational health in southern Italy.
AB  - The authors report the occupational medicine problems in the Apulia region, which
      are representative of those in Southern Italy. Late industrialization was
      associated with an early peak in injuries that was not associated with an
      increased workforce. Examples of operations adversely affecting worker and
      population health are presented.

PMID- 15859197
TI  - Industrial activities in sites at high environmental risk and their impact on the
      health of the population.
AB  - A second mortality analysis of 15 areas of Italy identified in 1986 by the
      Italian Ministry of Environment as areas at high risk of environmental crisis has
      confirmed and extended the findings of the first. In regional comparisons, these
      areas, in which potentially hazardous industries are located, show excesses of
      deaths from almost all cancers and other diseases, particularly among men.
      Although more information is needed to identify corrective public health
      measures, the official recognition of areas in need of cleaning up, which appears
      to be unique to Italy and which fostered the study, is a promising beginning.

PMID- 15859198
TI  - Health risk and occupation in agricultural settings in Italy.
AB  - In Italy several studies have examined the association between cancer and
      occupation in agricultural settings, focusing on exposure to pesticides. Most of
      the cohort studies evaluated cancer mortality in licensed pesticide users. Many
      case-control studies considered hematolymphopoietic malignancies, and the most
      recent studies observed increased risks for use of specific chemical classes of
      pesticides. Preliminary data on pesticide-related illnesses must be taken into
      account, and a national surveillance system should be implemented to identify
      areas at high risk and to promote exposure-control programs.

PMID- 15859199
TI  - Environment and respiratory diseases in childhood: the Italian experience.
AB  - To estimate the prevalence of respiratory disorders in children, and to
      investigate the roles of potential environmental risk factors, including exposure
      to outdoor air pollution, a large multicenter, population based survey (SIDRIA)
      was conducted in Italy in 1994-1995. The study enrolled more than 40,000
      children. Results allowed international comparisons of the prevalences of asthma
      and allergies in childhood in the framework of the ISAAC (International Study of
      Asthma and Allergies in Childhood) study, and supplied further evidence of the
      adverse respiratory effects of many environmental factors. The methods and main
      findings of the SIDRIA study are presented, focusing on the role of outdoor risk
      factors.

PMID- 15859201
TI  - The scarred earth.

PMID- 15859202
TI  - Back to square one. Government review repeats cold fusion conclusions.

PMID- 15859200
TI  - Meta-analysis of the Italian studies of short-term effects of air pollution
      (MISA), 1990-1999.
AB  - A meta-analysis of short-term effects of air pollution on health in eight Italian
      cities from 1990 to 1999 is presented. Death certificates and hospital admission
      data as well as daily concentrations of pollutants were collected. The same
      generalized linear model adjusted for age, day of the week, holidays, influenza
      epidemics, meteorological variables, and seasonality pattern was fitted to the
      city data. City-specific model selection was not done. In the meta-analysis, for
      each outcome, the city-specific estimates for each pollutant were combined using
      fixed and random-effects models. Hierarchical Bayesian models were use to
      investigate the effects of PM10 in detail. Each pollutant (SO2, NO2, CO, PM10,
      O3) was significantly associated with mortality for natural causes. The effect of
      PM10 on mortality was greater during the warm season and for elderly. A north
      south gradient in risk was observed for total natural mortality. The excess risks
      on hospital admission were modified by deprivation score and by the NO2/PM10
      ratio. Results add evidence for an association between air pollution and early
      mortality or morbidity and support the hypothesis of a synergism between
      meteorological variables and air pollution.

PMID- 15859203
TI  - The diet that fits.

PMID- 15859204
TI  - Rooting the river horse.

PMID- 15859206
TI  - Aerial base station.

PMID- 15859205
TI  - No bath time. In space, it's not easy being clean.

PMID- 15859207
TI  - Gay and lesbian census.

PMID- 15859208
TI  - The fossil fallacy.

PMID- 15859209
TI  - Behind the hockey stick.

PMID- 15859210
TI  - Misconceptions about the big bang.

PMID- 15859211
TI  - How did humans first alter global climate?

PMID- 15859213
TI  - On the road to fuel-cell cars.

PMID- 15859212
TI  - If smallpox strikes Portland....

PMID- 15859215
TI  - Inventor of dreams.

PMID- 15859214
TI  - Taming lupus.

PMID- 15859217
TI  - Digital photography. Take my pixel.

PMID- 15859216
TI  - Endangered wild equids.

PMID- 15859218
TI  - Apres-coup.

PMID- 15859219
TI  - On psychoanalytic writing.
AB  - Analytic writing constitutes a literary genre of its own. It involves the linking
      of an analytic idea (developed in a scholarly manner) with an analytic experience
      created in the medium of language. What makes this literary genre so demanding is
      that experience--including analytic experience--does not come to us in words.
      This fact generates a paradox that lies at the core of analytic writing: analytic
      experience (which cannot be said or written) must be transformed into 'fiction'
      (an imaginative rendering of experience in words) in order to convey to the
      reader something of what is true to the emotional experience that the analyst had
      with the patient. The author discusses a clinical passage from one of his
      recently published papers in an effort to demonstrate some of the conscious and
      unconscious thinking that goes into his writing. He then looks closely at the way
      the language works in a successful piece of theoretical analytic writing. The
      paper concludes with a discussion of a number of facets of the author s
      experience with analytic writing including the psychological 'state of writing',
      which is at once a meditation and a wrestling match with language; experimenting
      with the form (structure) of an analytic essay; and the question of originality
      in analytic writing.

PMID- 15859220
TI  - Does anything go? Towards a framework for the more transparent assessment of
      psychoanalytic competence.
AB  - It has been difficult to know what does and does not constitute competent
      psychoanalytic work and so equally difficult to assess when it is being practised
      and when it is not. This makes difficult any form of disciplined evaluation of
      the outcome of training, which has a series of problematic outcomes for
      psychoanalytic practice, psychoanalytic institutions and the relationship to
      allied disciplines and professions. In this paper, the author considers how far
      it might be possible to devise aframework for assessment of training programmes
      within a disciplined psychoanalytic pluralism. The aspiration is to develop a
      transparent framework, based on an empirically supported demonstration of
      analytic capacity. The framework needs to be sensitive and subtle, and to be able
      to withstand challenge. It needs to take cognisance of the twin facts that there
      is more than one way to practise psychoanalysis and that it is necessary to avoid
      'anything goes'. Drawing on an ongoing project undertaken by European IPA
      institutes, the author describes some of the problems colleagues have been
      experiencing in European institutes, because they have not had available
      transparent criteria for assessment. He outlines a preliminary form of a proposed
      method for making more transparent and supportable assessment. The author intends
      for this paper to inspire hope, enquiry and debate.

PMID- 15859221
TI  - Projective identification and consciousness alteration: a bridge between
      psychoanalysis and neuroscience?
AB  - The authors claim that projective identification in the process of analysis
      should be considered in a circumscribed manner and seen as a very specific type
      of communication between the patient and the analyst, characterised through a
      modality that is simultaneously active, unconscious and discrete. In other words,
      the patient actively, though unconsciously and discretely--that is, in specific
      moments of the analysis--brings about particular changes in the analysts state.
      From the analyst's side, the effect of this type of communication is a sudden
      change in his general state--a sense of passivity and coercion and a change in
      the state of consciousness. This altered consciousness can range from an almost
      automatic repetition of a relational script to a moderate or serious contraction
      of the field of attention to full-fledged changes in the analyst's sense of self.
      The authors propose the theory that this type of communication is, in fact, the
      expression of traumatic contents of experiences emerging from the non-declarative
      memory. These contents belong to a pre-symbolic and pre-representative area of
      the mind. They are made of inert fragments of psychic material that are felt
      rather than thought, which can thus be viewed as a kind of writing to be
      completed. These pieces of psychic material are the expression of traumatic
      experiences that in turn exercise a traumatic effect on the analyst, inducing an
      altered state of consciousness in him as well. Such material should be understood
      as belonging to an unrepressed unconscious. Restitution of these fragments to the
      patient in representable forms must take place gradually and without trying to
      accelerate the timing, in order to avoid the possibility that the restitution
      itself constitute an acting on the part of the analyst, which would thus be a
      traumatic response to the traumatic action of the analytic material.

PMID- 15859222
TI  - The preconscious and psychic change in Fairbairn's model of mind.
AB  - Fairbairn's mature model of mind was developed over a period of time and was
      modified significantly as it developed. In contrast to some sympathetic
      commentators who have suggested changes, the author has been impressed by the
      untapped potential of the theory. There are two areas that he feels need
      clarification and explanation, which are the importance of the preconscious, so
      neglected in our literature, and its role in psychic growth. By looking closely
      at the topographic categories and the way that Fairbairn uses them, the author
      has developed a modified version of Fairbairn's original model, which has a
      crucial role for a structured preconscious. The preconscious now becomes both a
      crucial original aspect of the early self and a significant, descriptively
      unconscious, fulcrum for both psychic change and mature dependence.

PMID- 15859223
TI  - What is the function of faith and trust in psychoanalysis?
AB  - Unlike other concepts such as 'illusion', 'capacity to tolerate frustration' and
      'libidinal investment', the concept of faith has not yet found a well-defined
      position in psychoanalytic theory. Bion focused on faith and placed it in an
      unusual context: scientific work. Through the Act of Faith a researcher can give
      some consistency to certain ideas, hunches or intuitions that may appear during
      observation, though he cannot represent them by existing theory. Through the Act
      of Faith an analyst can 'see', 'hear' and 'feel' those mental phenomena, the
      reality of which leaves no practising psychoanalysts in doubt, even if they
      cannot represent them by current formulations. In this paper, the author aims to
      expand Bion's proposals into the clinical and therapeutic fields. In the first
      part, the author examines how faith and trust overlap, and how they depart from
      each other; and he gives an example. Faith possesses an igniting and driving
      force which trust doesn't possess to the same extent. In the second part, the
      author looks at F as a psychic function of the analyst, which aids him in
      supporting a depressed and hopeless patient while waiting for the return of the
      patient s desire to live. In the final part, he focuses on F from the patient
      point of view and studies the transformations of F that may occur during an
      analysis.

PMID- 15859224
TI  - Freud's metapsychological speculations.
AB  - In this paper, the author seeks to analyse the nature and function of
      metapsychological theory in Freudian psychoanalysis. He shows that Freudian
      psychoanalytic theory is composed of an empirical part--the psychology of
      clinical facts--and a speculative part--metapsychology. Freud considers this
      latter part as being a speculative superstructure of value that is only
      heuristic, capable of being supplanted by other superstructures of the same type.
      The author sustains the idea that this metapsychology is the fruit of speculative
      method, whose foundations were elaborated by philosophers and epistemologists
      before Freud, including Immanuel Kant and Ernst Mach. He concludes with
      considerations regarding the future of metapsychological theorisation, presenting
      criticisms of Freudian metapsychology offered by both philosophers and
      psychoanalysts, and pointing to the perspective opened by Donald W. Winnicott of
      a psychoanalysis without metapsychology.

PMID- 15859225
TI  - Psychoanalytic application and psychoanalytic integrity.
AB  - In this article, the author offers an analysis of psychoanalytic application,
      defined as the breaking of new conceptual ground in some field of knowledge
      whereby the new idea is conceived, and later articulated, with the aid of
      reference to analogous phenomena in psychoanalysis. It requires apt analogy based
      on competent understanding of the applied field and of psychoanalysis. Only when
      the relevant differences between the applied and psychoanalytic fields are
      grasped can the extent of certain parallels emerge. The thinking by analogy that
      comprises psychoanalytic application may be intuitive and implicit, but should be
      susceptible of explicit theoretical elaboration that specifies, precisely, the
      point(s) of correspondence between psychoanalysis and the applied field in
      relation to a precise specification of their relevant differences. Applied
      psychotherapy at the interface of the internal and external worlds (historically
      rooted in casework) is employed as a model. By analogy with Donnet's concept of
      the analytic site, the author proposes the concept of the psychodynamic
      (case)work site, and elaborates it for that applied field in order to elucidate
      the proposed principles of psychoanalytic application.

PMID- 15859226
TI  - Psychoanalysis on the frontiers of terror: experiences in the USA, Israel and
      Peru.

PMID- 15859227
TI  - Can psychoanalysis and systematic research work productively together?

PMID- 15859229
TI  - Framing and interpretation in the analysis of adolescents.

PMID- 15859228
TI  - Biography, autobiography and history.

PMID- 15859230
TI  - Personality disorders: actings and rescue fantasies in cinema and psychoanalysis.

PMID- 15859231
TI  - Psychosexuality: the uses and abuses of excitement and its objects.

PMID- 15859232
TI  - Child psychoanalysis: how we work. Clinical models in practice: two clinical
      cases with detailed session material.

PMID- 15859233
TI  - Increased splenocyte mitogenesis following sympathetic denervation in Xenopus
      laevis.
AB  - Studies in mammals reveal that ablation of the sympathetic nervous system (SNS)
      can alter in vivo and in vitro parameters of immunity. To shed some light on the
      phylogenetic history of the interactions between the SNS and the immune system,
      we studied the effects of chemical sympathectomy on the proliferative response of
      frog splenocytes to mitogens. Adult Xenopus laevis were injected with 6
      hydroxydopamine 3 days before removal of spleen cells for culture with mitogens.
      Splenocytes from sympathectomized frogs exhibited an increased proliferative
      response to the T cell mitogens PHA and ConA and the B cell mitogen, LPS. That
      sympathectomy appears to effect a release from tonic inhibition by the SNS in
      Xenopus is consistent with comparable experiments in mice. It also reveals a
      phylogenetically ancient origin for SNS-immune system communications.

PMID- 15859234
TI  - Differential expression of FREP genes in two strains of Biomphalaria glabrata
      following exposure to the digenetic trematodes Schistosoma mansoni and
      Echinostoma paraensei.
AB  - Fibrinogen-related proteins (FREPs) are hypothesized to function in non-self
      recognition in the snail Biomphalaria glabrata. To investigate this assumption,
      the expression of four members of the FREP gene family was studied using
      quantitative PCR at 0.5-16 days following exposure of M line and BS-90 strain B.
      glabrata to Echinostoma paraensei and Schistosoma mansoni. Both strains react to,
      but fail to eliminate E. paraensei. Only the BS-90 strain is immunologically
      resistant to S. mansoni. Both snail strains responded to E. paraensei with
      significantly elevated expression of FREP 2 and 4. Following exposure to S.
      mansoni, resistant BS-90 snails showed an increase in expression of FREP 2 and 4
      (57-fold and 4.5-fold increase, respectively), susceptible M line snails did not
      display a FREP response. Expression of FREP 3 and 7 was not significantly
      elevated in any snail/trematode combination. These expression profiles support
      the hypothesis that some FREPs play a role in the anti-trematode responses in B.
      glabrata.

PMID- 15859235
TI  - Superoxide dismutase expression and H2O2 production by hemocytes of the trematode
      intermediate host Lymnaea stagnalis (Gastropoda).
AB  - Snail hemocytes mobilise ROS-generating enzymes during oxidative burst similar to
      those of mammalian leukocytes. We report herein the identification of an
      inducible Cu/Zn superoxide dismutase, which converts O2- to H2O2, in hemocytes of
      the pond snail Lymnaea stagnalis. The deduced amino acid sequence with all
      characteristic residues (His44,46,61,69,78 and 118, Asp81, Cys55/144, Arg141 and
      the Greek Key loop region Glu119-Leu/Val142) includes an open reading frame of
      155 AA. Changes in Cu/ZnSOD gene expression induced by stimulation with Zymosan
      or trematode larvae were examined in a time course. Activated hemocytes
      significantly up-regulate Cu/ZnSOD expression during 2-48 h upon stimulation with
      the maximal induction at 45 min during phagocytosis and at 12 h during
      encapsulations. This increase in Cu/ZnSOD expression paralleled the increasing
      production of hydrogen peroxide by hemocytes. Thus, intracellular or
      extracellular targets elicit an induced expression of Cu/ZnSOD and the generation
      of elevated amounts of hydrogen peroxide by L. stagnalis hemocytes, reflecting a
      significant activation of their host defense function.

PMID- 15859236
TI  - In vivo exposure of clearnose skates, Raja eglanteria, to ionizing X-radiation:
      acute effects on the thymus.
AB  - To investigate for the first time the effects of ionizing radiation on thymus of
      a representative cartilaginous fish, juvenile clearnose skates, Raja eglanteria,
      were exposed to 0-75 Gy of X-radiation and sacrificed after 12 days.
      Morphometrics (weight, disc width and total length) and thymus and thymic cyst
      area were compared to controls using ANOVA. Thymus area declined logarithmically
      and medullary cysts increased as a function of dose (P < or = 0.05). To assess
      thymic recovery, skates were exposed to 0, 9, 13.5 or 18 Gy of X-radiation and
      sacrificed when moribund or on days 10, 20, 30 and 40 post-irradiation. Complete
      restoration of the thymus was not achieved during the 40-day observation period,
      although repopulation with pro-thymocytes and partial recovery of thymic
      architecture were evident histologically. The observed high radiosensitivity of
      R. eglanteria thymocytes was similar to responses of other vertebrates, but
      recovery time was prolonged.

PMID- 15859237
TI  - Identification of genes differentially expressed in Atlantic salmon (Salmo salar)
      in response to infection by Aeromonas salmonicida using cDNA microarray
      technology.
AB  - The response of Atlantic salmon, Salmo salar, to infection by the bacterial
      pathogen Aeromonas salmonicida (the causative agent of furunculosis), was
      investigated using a cohabitation model and a custom Atlantic salmon cDNA
      microarray consisting of over 4000 different amplicons. Pooled samples of each of
      three immune-relevant tissues (spleen, head kidney and liver) were obtained from
      fish exposed to infected salmon for 13 days. Reverse transcription-PCR assays
      were used to verify the differential expression of 12 candidate genes uncovered
      by microarray analysis. Among the differentially expressed genes were several
      previously revealed by suppression subtractive hybridization and EST surveys and
      that are recognized to encode humoral components of the innate immune system.
      Other genes identified in this study were not previously associated with
      infection. In addition, a number of genes with no known homologs were uncovered.
      Determination of their specific roles during infection may lead to a better
      understanding of innate immunity.

PMID- 15859238
TI  - Characterization and expression analysis of the chicken interleukin-11 receptor
      alpha chain.
AB  - Interleukin-11 (IL-11) is a multifunctional cytokine involved in various pathways
      in blood cells, their precursors and many other cell types in vitro and in vivo.
      The effects of IL-11 are largely mediated by the IL-11 receptor alpha-chain (IL
      11Ralpha). In this study, a putative cDNA sequence encoding the 414 amino acid
      propeptide of chicken IL-11R (chIL-11R) was identified. The predicted 414 amino
      acid sequence showed 42-43% sequence identity with mammalian homologues. In a
      domain search of the molecule, two fibronectin (FN) type-III domains were
      identified in the C- terminal portion. On comparison with mammalian IL-11R, 4
      conserved cysteine residues and a WSXWS motif were observed within the FN type
      III domains. Expression analysis revealed that chIL-11Ralpha is strongly
      expressed in brain, heart, lung, liver, glandular stomach, kidney, the immature
      testis, ovary and chicken blastodermal cells (CBCs) after 1-day-cultivation.
      These findings strongly indicate that the identified chicken cDNA sequence
      encodes chIL-11R alpha-chain homologue.

PMID- 15859239
TI  - Conservation of biological properties of the CD40 ligand, CD154 in a non
      mammalian vertebrate.
AB  - Signals delivered by the CD40 ligand, CD154, have crucial roles in immune
      responses in mammals, being required for development of germinal centres,
      maturation of T-dependent antibody responses, and generation of B-cell memory. To
      determine whether these functions were conserved in a non-mammalian species, a
      putative chicken CD 154 cDNA was used to make an oligomeric fusion protein, and
      to raise monoclonal antibodies. The antibodies detected surface expression on
      activated T-cells. The fusion protein detected expression of a receptor on B
      cells, thrombocytes and macrophages. Biological effects of the fusion protein
      included induction of NO synthesis in a macrophage cell line, enhancement of
      splenic B-cell survival, and induction of apoptosis in a bursal lymphoma cell
      line. These observations demonstrated substantial functional equivalence with
      mammalian CD 154 and thus provided evidence for the early evolutionary emergence
      of the set of functions associated with this molecule, and its central role in
      the vertebrate immune system.

PMID- 15859240
TI  - Recombinant chicken IL-6 does not activate heterophils isolated from day-old
      chickens in vitro.
AB  - Pro-inflammatory cytokines are produced as part of innate immunity. Increased
      resistance to extraintestinal Salmonella enteritidis (SE) has been associated
      with an increase in heterophil pro-inflammatory cytokine gene expression.
      Invasion of chicken epithelial cells by SE induces an 8- to 10-fold increase in
      interleukin (IL) -6 production. Infection with SE induces an influx of
      heterophils to the site of infection; therefore, we hypothesize heterophils would
      be responsive to IL-6. The objective was to determine the effects of COS cell
      derived recombinant chicken interleukin 6 (rChIL-6) on in vitro functional
      activity of heterophils. Heterophils were incubated with rChIL-6 or mock
      transfected COS cell supernatant and functional activity was assessed.
      Heterophils treated with rChIL-6 showed no functional differences compared to
      controls. These data indicate rChIL-6, alone, does not affect the functional
      activity of neonatal chicken heterophils in vitro. Therefore, the function of IL
      6 in the local environment in response to SE invasion is still unknown.

PMID- 15859241
TI  - Preface forum: "functional insight from physical methods on metalloenzymes".

PMID- 15859242
TI  - Spectroscopic approaches to elucidating novel iron-sulfur chemistry in the
      "radical-Sam" protein superfamily.
AB  - Electron paramagnetic resonance (EPR), electron-nuclear double resonance (ENDOR),
      and Mossbauer spectroscopies and other physical methods have provided important
      new insights into the radical-SAM superfamily of proteins, which use iron-sulfur
      clusters and S-adenosylmethionine to initiate H atom abstraction reactions. This
      remarkable chemistry involves the generation of the extremely reactive 5'
      deoxyadenosyl radical, the same radical intermediate utilized in B12-dependent
      reactions. Although early speculation focused on the possibility of an
      organometallic intermediate in radical-SAM reactions, current evidence points to
      novel chemistry involving a site-differentiated [4Fe-4S] cluster. The focus of
      this forum article is on one member of the radical-SAM superfamily, pyruvate
      formate-lyase activating enzyme, and how physical methods, primarily EPR and
      ENDOR spectroscopies, are contributing to our understanding of its structure and
      mechanism. New ENDOR data supporting coordination of the methionine moiety of SAM
      to the unique site of the [4Fe-4S]2+/+ cluster are presented.

PMID- 15859243
TI  - Rapid freeze-quench 57Fe Mossbauer spectroscopy: monitoring changes of an iron
      containing active site during a biochemical reaction.
AB  - Nuclear gamma resonance spectroscopy, also known as Mossbauer spectroscopy, is a
      technique that probes transitions between the nuclear ground state and a low
      lying nuclear excited state. The nucleus most amenable to Mossbauer spectroscopy
      is 57Fe, and 57Fe Mossbauer spectroscopy provides detailed information about the
      chemical environment and electronic structure of iron. Iron is by far the most
      structurally and functionally diverse metal ion in biology, and 57Fe Mossbauer
      spectroscopy has played an important role in the elucidation of its biochemistry.
      In this article, we give a brief introduction to the technique and then focus on
      two recent exciting developments pertaining to the application of 57Fe Mossbauer
      spectroscopy in biochemistry. The first is the use of the rapid freeze-quench
      method in conjunction with Mossbauer spectroscopy to monitor changes at the Fe
      site during a biochemical reaction. This method has allowed for trapping and
      subsequent detailed spectroscopic characterization of reactive intermediates and
      thus has provided unique insight into the reaction mechanisms of Fe-containing
      enzymes. We outline the methodology using two examples: (1) oxygen activation by
      the non-heme diiron enzymes and (2) oxygen activation by taurine:alpha
      ketoglutarate dioxygenase (TauD). The second development concerns the calculation
      of Mossbauer parameters using density functional theory (DFT) methods. By using
      the example of TauD, we show that comparison of experimental Mossbauer parameters
      with those obtained from calculations on model systems can be used to provide
      insight into the structure of a reaction intermediate.

PMID- 15859244
TI  - Resonance raman investigation of the specific sensing mechanism of a target
      molecule by gas sensory proteins.
AB  - Specific sensing of gas molecules such as CO, NO, and O2 is a unique function of
      gas sensory hemoproteins, while hemoproteins carry out a wide variety of
      functions such as oxygen storage/transport, electron transfer, and catalysis as
      enzymes. It is important in gas sensory proteins that the heme domain not only
      recognizes its target molecule but also discriminates against other gases having
      similar molecular structures. Coordination of a target molecule to the heme is
      assumed to alter the protein conformation in the vicinity of heme, and the
      conformation change is propagated to the effector domain where substrate
      turnover, DNA binding, or interaction with a signal transduction protein is
      performed differently than the binding of other gases. To understand the
      appearance of such a specificity, we focus our attention on the ligand-protein
      interactions in the distal side of heme. In practice, the metal-ligand vibrations
      as well as internal modes of ligand and heme are measured with resonance Raman
      spectroscopy for wild-type and some mutant proteins with full-length or limited
      sensory regions. On the basis of such observations together with the knowledge
      currently available, we discuss the mechanism of specific sensing of a diatomic
      molecule in gas sensory proteins.

PMID- 15859245
TI  - X-ray crystallography and biological metal centers: is seeing believing?
AB  - Metalloenzyme crystal structures have a major impact on our understanding of
      biological metal centers. They are often the starting point for mechanistic and
      computational studies and inspire synthetic modeling chemistry. The strengths and
      limitations of X-ray crystallography in determining properties of biological
      metal centers and their corresponding ligand spheres are explored through
      examples, including ribonucleotide reductase R2 and particulate methane
      monooxygenase. Protein crystal structures locate metal ions within a protein fold
      and reveal the identities and coordination geometries of amino acid ligands. Data
      collection strategies that exploit the anomalous scattering effect of metal ions
      can establish metal ion identity. The quality of crystallographic data,
      particularly the resolution, determines the level of detail that can be extracted
      from a protein crystal structure. Complementary spectroscopic techniques can
      provide crucial information regarding the redox state of the metal center as well
      as the presence, type, and protonation state of exogenous ligands. The final
      result of the crystallographic characterization of a metalloenzyme is a model
      based on crystallographic data, supported by information from biophysical and
      modeling studies, influenced by sample handling, and interpreted carefully by the
      crystallographer.

PMID- 15859246
TI  - Paramagnetic NMR spectroscopy and density functional calculations in the analysis
      of the geometric and electronic structures of iron-sulfur proteins.
AB  - Paramagnetic NMR spectroscopy has been underutilized in the study of
      metalloproteins. One difficulty of the technique is that paramagnetic relaxation
      broadens signals from nuclei near paramagnetic centers. In systems with low
      electronic relaxation rates, this makes such signals difficult to observe or
      impossible to assign by traditional methods. We show how the challenges of
      detecting and assigning signals from nuclei near the metal center can be overcome
      through the combination of uniform and selective 2H, 13C, and 15N isotopic
      labeling with NMR experiments that utilize direct one-dimensional (2H, 13C, and
      15N) and two-dimensional (13C-X) detection. We have developed methods for
      calculating NMR chemical shifts and relaxation rates by density functional theory
      (DFT) approaches. We use the correspondence between experimental NMR parameters
      and those calculated from structural models of iron-sulfur clusters derived from
      X-ray crystallography to validate the computational approach and to investigate
      how structural differences are manifested in these values. We have applied this
      strategy to three iron-sulfur proteins: Clostridium pasteurianum rubredoxin,
      Anabaena [2Fe-2S] ferredoxin, and human [2Fe-2S] ferredoxin. Provided that an
      accurate structural model of the iron-sulfur cluster and surrounding residues is
      available from diffraction data, our results show that DFT calculations can
      return NMR observables with excellent accuracy. This suggests that it might be
      possible to use calculations to refine structures or to generate structural
      models of active sites when crystal structures are unavailable. The approach has
      yielded insights into the electronic structures of these iron-sulfur proteins. In
      rubredoxin, the results show that substantial unpaired electron spin is
      delocalized across NH...S hydrogen bonds and that the reduction potential can be
      changed by 77 mV simply by altering the strength of one of these hydrogen bonds.
      In reduced [2Fe-2S] ferredoxins, hyperfine shift data have provided quantitative
      information on the degree of valence trapping. The approach described here for
      iron-sulfur proteins offers new avenues for detailed studies of these and other
      metalloprotein systems.

PMID- 15859247
TI  - Investigating metalloenzyme reactions using electrochemical sweeps and steps:
      fine control and measurements with reactants ranging from ions to gases.
AB  - Protein film voltammetry is a powerful method for probing the chemistry of redox
      active sites in metalloproteins. The technique affords precise potential control
      over a tiny quantity of material that is manipulated on an electrode surface,
      providing information on ligand- or metal-exchange reactions coupled to electron
      transfer. This is illustrated by examples of transformations of the iron-sulfur
      clusters in ferredoxins. Protein film voltammetry is particularly advantageous in
      studies of metalloenzymes for which the current response is proportional to
      catalytic activity: kinetic data of extremely high signal/noise ratio are
      obtained for highly active enzymes. We present a series of interesting examples
      in which catalytic activity varies in unusual ways with applied potential,
      surveying information that can be obtained from cyclic voltammetry and then
      looking beyond this method to controlled potential-step experiments that yield
      kinetic and mechanistic details. Recent results on the voltammetry of the highly
      active [NiFe]-hydrogenase from Allochromatium vinosum illustrate how it is
      possible to use the precise kinetic information from potential-step experiments
      to diagnose subtle details of transformations between catalytically active and
      inactive states of an enzyme. Protein film voltammetry thus complements
      spectroscopic techniques and other physical methods, revealing the chemistry of
      systems that might appear intractable or convoluted by other means.

PMID- 15859248
TI  - Flexible eightfold interpenetrating diamondoid network generating 1D channels:
      selective binding with organic guests.
AB  - An 8-fold interpenetrating diamondoid network, [Ni(cyclam)]2[TCM]. 2DMF x 10H2O,
      has been prepared by the self-assembly of a Ni-(II)cyclam macrocyclic complex and
      sodium tetrakis[4-(carboxyphenyl)-oxamethyl]methane in DMF/water. The network
      shows an unusual [4 + 4] mode of interpenetration, generating 1D channels of
      effective window size 6.7 A x 4.7 A. The network shows flexible behavior: it
      becomes nonporous on removal of the guest molecules occupying the channels, but
      the open structure is restored when the desolvated solid is immersed in the
      mixture of H2O/DMF (1:1, v/v) for 5 min. The desolvated host has different
      binding capacities for n-butanol, pyridine, and ethanol.

PMID- 15859249
TI  - Uranyl-peptide interactions in carbonate solution with DAHK and derivatives.
AB  - Metal-peptide complexes in a 1:1 ratio between the uranyl cation (UO2(2+)) and
      the peptides, DAHK or GGH, are observed in the gas phase (ESI-MS). Solution state
      studies with the same peptides and variants, DGHG, AcDGHG, and DAHKSE-CONH2,
      indicate that peptide-carboxylato donors can coordinate to the uranyl
      biscarbonato complex. UV-vis and fluorescence spectra of uranyl carbonate exhibit
      significant changes or quenching upon addition of peptide. NMR titration data
      were used to determine conditional association constants, log K = 2.2+/-0.4 and
      log K = 3.1+/-0.4, for the [UO2(CO3)2(GGH)] and [UO2(CO3)2(DAHK)] species,
      respectively. Uranyl asymmetric stretching frequencies for uranyl/ DAHKSE-CONH2
      (v3 = 914 cm(-1)) and uranyl/DAHK (v3 = 908 cm(-1)) complexes and other infrared
      spectral features are also consistent with peptide-carboxylato coordination.

PMID- 15859250
TI  - An infinite water chain passes through an array of Zn(II) metallocycles built
      with a podand bearing terminal carboxylates.
AB  - A podand bearing three carboxylic acid groups was synthesized by condensation of
      tris(2-chloroethyl)amine with 4-hydroxyethylbenzoate followed by hydrolysis of
      the ester group. An aqueous solution of Zn(NO3)2 x 6H2O reacts with the
      tetraethylammonium salt of the podand at room temperature, to form a porous
      coordination polymeric structure with infinite interlinked chains of Zn(II)
      metallocycles. An infinite water chain passes through the metallocycles like a
      thread. The compound was characterized by X-ray crystallography, X-ray powder
      diffraction, TGA, IR spectroscopy, and elemental analysis.

PMID- 15859251
TI  - The first example of solvothermally synthesized thioantimonates(V) with
      ethylenediamine coordinated lanthanide(III): [Sm(en)4]SbS4 x 0.5en and
      [Sm(en)3(H2O)(micro-SbS4)]infinity.
AB  - Under mild solvothermal conditions two novel thioantimonates(V) [Sm(en)4]SbS4 x
      0.5en (1) and [Sm(en)3(H2O)(micro-SbS4)]infinity (2) were synthesized; the
      structure of 1 contains discrete [Sm(en)4]3+ and [SbS4]3 ions, while 2 consists
      of neutral [Sm(en)3(H2O) (micro-SbS4)] one-dimensional chains.

PMID- 15859252
TI  - Ditopic macropolycyclic complexes: synthesis of hybrid
      phthalocyaninoclathrochelates.
AB  - A remetalation (a capping group exchange) reaction of the boronantimony-capped
      iron(II) clathrochelates with zirconium and hafnium(IV) phthalocyanines in
      CH2Cl2/CH3OH medium afforded the hybrid phthalocyaninoclathrochelates in a
      practically quantitative yield. The complexes obtained have been characterized
      both on the basis of elemental analysis, PD mass spectrometry, IR, UV-vis, 57Fe
      Mossbauer, and NMR spectroscopies, and crystallographically. An encapsulated
      iron(II) ion in an intermediate between a trigonal-prismatic and a trigonal
      antiprismatic environment of six nitrogen atoms of the macrobicyclic ligand was
      found to be in a low-spin state. The cyclic voltammograms show irreversible
      oxidation and reduction waves assignable to Fe+/Fe2+ couples of macrobicyclic
      fragments and to phthalocyanine macrocycles.

PMID- 15859253
TI  - Photocleavage of lysozyme by cobalt(III) complexes.
AB  - Photochemical reagents that cleave proteins at specific sites (photoproteases)
      are useful for studying protein structure and protein-ligand interactions.
      PolyammineCo(III) complexes are tested here as photochemical probes to cleave
      proteins. Irradiation of a mixture of lysozyme, a model protein, and
      polyammineCo(III) complexes resulted in the facile cleavage of the peptide
      backbone. Photocleavage yielded two fragments of molecular weights 10.6 and 3.7
      kDa, and these masses sum to the molecular mass of lysozyme (14.3 kDa). No
      cleavage was detected in the absence of the metal complex, in the dark, or upon
      irradiation at wavelengths of >420 nm. The photocleavage yield increased with
      irradiation time and with the concentrations of the metal complex and the
      protein. N-terminal sequencing of the 10.6 kDa fragment indicated residues that
      are identical to the N-terminus of lysozyme, and sequencing of the 3.7 kDa
      fragment indicated Val-Ala-Trp-Arg, an internal sequence of lysozyme. From the
      known primary sequence of lysozyme and the sequencing data, the cleavage site was
      assigned to Trp108-Val109. Molecular modeling indicates that the observed
      cleavage site is within few angstroms from the proposed metal binding site at
      Glu35-Asp52. This is the first report of the successful photocleavage of
      proteins, with high selectivity, by transition metal complexes. This novel
      observation can facilitate the rational design of transition metal complexes for
      the photochemical footprinting of metal binding sites on proteins.

PMID- 15859254
TI  - A zinc carboxylate network containing metal sites with low coordination numbers.
AB  - A bifunctional m-terphenyl, 2,6-diphenyl-1,4-dibenzoic acid (Ph2BDC), was
      synthesized and used in the preparation of a 2-D metal-organic coordination
      polymer. The steric hindrance of the bulky bifunctional linker forces low
      coordination at the Lewis-acidic zinc center. A zinc carboxylate dimer was
      prepared as a model compound to examine the unusual tricoordinate geometry at the
      metal site.

PMID- 15859255
TI  - Anions or cations: who is in charge of inhibiting the nickel(II) promoted B- to Z
      DNA transition?
AB  - Various weakly binding cations and anions were studied at a concentration of 10
      mM to ascertain their interaction with the nickel(II) promoted B- to Z-DNA
      transition of poly d(GC). These salts were ranked according to the decreasing
      amounts of nickel needed for the B- to Z-DNA transition and provided the
      following order: NaCl approximately Me4NCl > LiCl >> MgCl2 > no salt > NaBF4
      approximately NaNO3 approximately NaClO4. Remarkably, it was found that going
      from sodium nitrate to sodium chloride increased the necessary amount of nickel
      to induce the transition to the left-handed helix of poly d(GC) by a factor of
      10. This dramatic effect cannot be explained by the binding constant of
      nickel(II) to chloride to form the monocationic complex. We believe that this is
      the first reported example of the role of chloride anions, which appear to
      modulate the interaction of nickel(II) ions with the polyanionic DNA.

PMID- 15859256
TI  - Mono- and dinuclear tricarbonyltechnetium(I) complexes with thiosemicarbazones.
AB  - [NEt4]2[Tc(CO)3Cl3] reacts with thiosemicarbazones derived from 2,2'-dipyridyl
      ketone (HL3) and 4-acetylpyridine (HL4) to form stable technetium(I) complexes of
      the compositions [Tc(CO)3Cl(HL3-Npy,Npy)] and [Tc2(CO)6Cl2(micro-HL4-Npy,S)].
      Whereas exclusively the pyridine nitrogen atoms are involved in coordination in
      the monomeric complex, the binuclear compound represents the first technetium
      complex with a coordinated thiosemicarbazone functionality.

PMID- 15859257
TI  - Assembly of hydrogen bonded diamondoid networks based on synthetic metal-organic
      tetrahedral nodes.
AB  - Reaction of Mn(ClO4)2 or Co(PF6)2 with 4,4'-dipyridine-dioxide (dpdo) produced
      novel molecular species [M(dpdo)4(H2O)2]2+, which hold a tetrahedral
      configuration notwithstanding their octahedral environment around the metal
      centers. The tetrahedral moieties are further assembled through hydrogen bonds
      between peripheral NO ends of dpdo ligands and coordinated water molecules,
      giving rise to 3D diamondoid networks.

PMID- 15859258
TI  - Structure and emission properties of Er3Q9 (Q = 8-quinolinolate).
AB  - We report the first combined optical and structural investigation of the water
      free Er-quinolinolate complex, an organo-lanthanide system of interest for 1.5
      microm telecom applications. Structural data demonstrate that the complex has a
      trinuclear structure (Er3Q9) which provides the Er metals with an octa
      coordination by the organic ligand and prevents solvent and water molecules from
      entering the lanthanide coordination sphere. The results of the structural
      analysis allow us to infer that the strong Er luminescence quenching exhibited by
      the Er3Q9 complex is due uniquely to resonant energy transfer to the aromatic C-H
      vibrations of the ligand, providing the correct tools to design more efficient
      emitters.

PMID- 15859259
TI  - Violation of the isolated square rule for group 13-15 oligomers: theoretical
      prediction of a new class of inorganic polymers.
AB  - It is widely thought that the oligomer compounds [RMYR]n (M-group 13, Y-group 15
      element) should obey the isolated square rule found for the boron-nitrogen cages.
      In contrast to these expectations, the needle-shaped oligomers, which violate
      this rule, are more stable compared to the cage (fullerene-like) oligomers for
      all MY pairs (M = B, Al, Ga, In; Y = N, P, As). The stability of the needle
      shaped clusters improves with increasing oligomerization degree. Thus, the
      isolated square rule, which is analogous to the isolated pentagon rule widely
      applied for fullerenes, should not serve as the basis for searches for the most
      stable structures of the inorganic oligomers. Generation of the needle-shaped
      oligomers from the group 13 and 15 hydrides is thermodynamically favorable. A
      synthesis of novel inorganic polymers, formed by fusion of trimeric M3Y3 rings,
      is expected to be viable.

PMID- 15859260
TI  - The first nitro-substituted heteroscorpionate ligand.
AB  - The new dihydridobis(3-nitro-1,2,4-triazolyl)borate ligand, [H2B(tzNO2)2]-, has
      been synthesized in dimethylacetamide solution, using 3-nitro-1,2,4-triazole and
      KBH4 through careful temperature control, and characterized as its potassium
      salt. The zinc(II) and cadmium(II) complexes, {M[H2B(tzNO2)2]Cl(H2O)2}, have been
      prepared by metathesis of [H2B(tzNO2)2]K with ZnCl2 and CdCl2, respectively. The
      complexes likely contain a metal core in which the ligand is coordinated to the
      metal ions in the K2-N,N' or K4-N,N',O,O' fashion. A single-crystal structural
      characterization is reported for the potassium dihydrobis(3-nitro-1,2,4
      triazolyl)borate. The potassium salt is polymeric and shows several K...N and
      K...O interactions.

PMID- 15859261
TI  - Tuning of luminescence spectra of neutral ruthenium(II) complexes by crystal
      waters.
AB  - Neutral ruthenium(II) complexes [RuLL'(CN)2] (L, L' = bpy, dmb, dbb; bpy = 2,2'
      bipyridine, dmb = 4,4'-dimethyl-2,2'-bipyridine, dbb = 4,4'-tert-butyl-2,2'
      bipyridine) were prepared, and the luminescence characteristics of the complexes
      in the solid state were measured. The luminescence was tuned by crystal waters
      included in the crystals; for example, [Ru(dbb)2(CN)2] x 2H2O, [Ru(dbb)2(CN)2] x
      H2O, and [Ru(dbb)2(CN)2] emit luminescence at 640, 685, and 740 nm, respectively.

PMID- 15859262
TI  - Uranyl complexation in fluorinated acids (HF, HBF4, HPF6, HTf2N): a combined
      experimental and theoretical study.
AB  - The aim of this work is to characterize the complexation ability of F-, BF4-, PF6
      , and Tf2N- toward uranyl ions in aqueous solution. These anions were chosen as
      they represent the anionic part of the most studied room-temperature ionic
      liquids. Time-resolved emission spectroscopy and X-ray absorption spectroscopy
      were used to retrieve structural data on the complexes formed. The results
      obtained were compared with computational data. Tf2N- does not complex uranyl,
      even at high concentration. Other fluorinated acids form inner-sphere complexes
      with U(VI), in a monodentate fashion in the case of BF4- and PF6-.

PMID- 15859263
TI  - Coordination polymers based on inorganic lanthanide(II) sulfate skeletons and an
      organic isonicotinate N-oxide connector: segregation into three structural types
      by the lanthanide contraction effect.
AB  - Fourteen three-dimensional coordination polymers of general formula
      [Ln(lNO)(H2O)(SO4)]n, where Ln = La, 1.La; Ce, 2.Ce; Pr, 3.Pr; Nd, 4.Nd; Sm,
      5.Sm; Eu, 6.Eu; Gd, 7.Gd; Tb, 8.Tb; Dy, 9.Dy; Ho, 10.Ho; Er. 11.Er; Tm, 12.Tm;
      Yb, 13.Yb; and Lu, 14.Lu; INO = isonicotinate-N-oxide, have been synthesized by
      hydrothermal reactions of Ln3+, MnCO3, MnSO4 x H2O, and isonicotinic acid N-oxide
      (HINO) at 155 degrees C and characterized by single-crystal X-ray diffraction,
      IR, thermal analysis, luminescence spectroscopy, and the magnetic measurement.
      The structures are formed by connection of layer, chain, or dimer of Ln-SO4 by
      the organic connector, INO. They belong to three structural types that are
      governed exclusively by the size of the ions: type I for the large ions, La, Ce,
      and Pr; type II for the medium ions, Nd, Sm, Eu, Gd, and Tb; and type III for the
      small ions, Dy, Ho, Er, Tm, Yb, and Lu. Type I consists of two-dimensional
      undulate Ln-sulfate layers pillared by INO to form a three-dimensional network.
      Type II has a 2-fold interpenetration of "3D herringbone" networks, in which the
      catenation is sustained by extensive pi-pi interactions and O-H...O and C-H...O
      hydrogen bonds. Type III comprises one-dimensional chains that are connected by
      INO bridges, resulting in an alpha-Po network. The progressive structural change
      is due to the metal coordination number decreasing from nine for the large ions
      via eight to seven for the small ions, demonstrating clearly the effect of
      lanthanide contraction. The sulfate ion acts as a micro4- or micro3-bridge,
      connecting two, three, or four metals, and is both mono- and bidentate. The INO
      ligand acts as a micro3- or micro2-bridge with carboxylate group in syn-syn
      bridging or bidentate chelating mode. The materials show considerably high
      thermal stability. The magnetic properties of 4.Nd, 6.Eu, 7.Gd, and 13.Yb and the
      luminescence properties of 6.Eu and 8.Tb are also investigated.

PMID- 15859264
TI  - N2S2Ni metallodithiolate complexes as ligands: structural and aqueous solution
      quantitative studies of the ability of metal ions to form M-S-Ni bridges to
      mercapto groups coordinated to nickel(II). implications for acetyl coenzyme A
      synthase.
AB  - The nickel(II) complex of an N2S2 ligand, derived from a diazacycle, N,N'
      bis(mercaptoethyl)-1,5-diazacycloheptane, (bme-dach)Ni, Ni-1', serves as a
      metallodithiolate ligand to NiII, CuI, ZnII, Ag, and PbII. The binding ability of
      the NiN2S2 ligand to the metal ions was established through spectrochemical
      titrations in aqueous media and compared to classical S-donor ligands. For M =
      Ni, Zn, Pb, binding constants, log K = ca. 2. were computed for 1:1 Ni
      1'/M(solvate) adducts; for Ag+ and Cu+, the 3:2 (Ni-1')3M2 adducts were the first
      formed products even in water with log beta3,2 values of 26 and >30,
      respectively. In all cases, the binding ability of Ni-S-R is intermediate between
      that of a free thiolate and a free thioether. The great specificity for copper
      over nickel and zinc by N2S2Ni, which serves as a reasonable structural model for
      the distal nickel of the acetyl CoA synthase active site, relates to biochemical
      studies of heterogeneity (metal content and type) in various preparations of
      acetyl CoA synthase enzyme.

PMID- 15859265
TI  - Examining the out-of-center distortion in the [NbOF5]2- anion.
AB  - Out-of-center "primary" electronic distortions are inherent to the oxide fluoride
      anions of the early d0 transition metals. In the [NbOF5]2- anion, the Nb5+ moves
      from the center of the octahedron toward the oxide ligand to form a short Nb=O
      bond and long trans Nb-F bond. The combined results of single-crystal X-ray
      diffraction and electronic structure calculations indicate that the primary
      distortion of the [NbOF5]2- anion is affected by the coordination environment
      that is created by the three-dimensional extended structure. The formation of
      bonds between an M(L)4(2+) (M = Cd2+, Cu2+; L = 3-aminopyridine, 4-aminopyridine)
      cation and the oxide and/or trans-fluoride ligands of the [NbOF5]2- anion weakens
      the pi component of the Nb=O bond. At the same time, hydrogen bond interactions
      between the equatorial fluorides and the aminopyridine groups both lengthen the
      equatorial Nb-F bonds and can further reduce the symmetry of the [NbOF5]2- anion.
      These combined three-dimensional bond network interactions that serve to lengthen
      the Nb=O bond and thereby decrease the primary distortion of the [NbOF5]2- anion
      are illustrated in the structures of three new niobium oxide fluoride phases, [4
      apyH]2[Cu(4-apy)4(NbOF5)2] (4-apy = 4-aminopyridine), Cd(3-apy)4NbOF5 (3-apy = 3
      aminopyridine), and Cu(3-apy)4NbOF5, that were synthesized and characterized
      using X-ray diffraction. Crystal data for [4-apyH]2[Cu(4-apy)4(NbOF5)2]:
      tetragonal, space group /4(1)/ acd (No. 142), with a = 20.8745(8) A, c =
      17.2929(9) A, and Z= 8. Cd(3-apy)4NbOF5: tetragonal, space group P4(3) (No. 78),
      with a = 8.4034(4) A, c = 34.933(3) A, and Z = 4. Cu(3-apy)4NbOF5: monoclinic,
      space group P2(1)/n (No. 14), with a = 8.822(1) A, b = 16.385(3) A, c = 8.902(1)
      A, beta = 109.270(3) degrees, and Z = 2.

PMID- 15859266
TI  - Structure, electrochemistry, and magnetism of the iron(III)-substituted Keggin
      dimer, [Fe6(OH)3(A-alpha-GeW9O34(OH)3)2]11-.
AB  - The iron(III)-substituted tungstogermanate [Fe6(OH)3(A-alpha-GeWO34(OH)3)2]11-
      (1) has been synthesized and characterized by IR, elemental analysis, SQUID
      magnetometry, electron paramagnetic resonance (EPR), and electrochemistry. Single
      crystal X-ray analysis was carried out on Cs4Na7[Fe6(OH)3(A-alpha-GeW9O34(OH)3)2]
      x 30H2O, which crystallizes in the monoclinic system, space group C2/m, with a =
      36.981(4) A, b = 16.5759(15) A, c = 16.0678(15) A, beta = 95.311(3) degrees, and
      Z = 4. Polyanion 1 consists of two (A-alpha-GeW9O34) Keggin moieties linked via
      six Fe3+ ions, leading to a double-sandwich structure. The equivalent iron
      centers represent a trigonal prismatic Fe6 fragment, resulting in virtual D3h
      symmetry for 1. Electrochemistry studies revealed that 1 is stable in solution
      from pH 3 to at least pH 7. In pH = 3 media the reduction of the six Fe3+ centers
      was featured by a single voltammetric wave for most supporting electrolytes used.
      In that case, whatever the scan rate from 1000 mV x s(-1) down to 2 mV x s(-1),
      no splitting of the single Fe-wave of 1 was observed. The acetate medium induced
      a partial splitting of the wave, and this separation is enhanced with increasing
      pH. Remarkable efficiency of 1 in the electrocatalytic reduction of nitrite,
      nitric oxide, and nitrate is demonstrated. Magnetic susceptibility (chi)
      measurements indicate a diamagnetic (S(T) = 0) ground state, with an average J = 
      12 cm(-1) and g = 2.00. EPR studies confirm that the ground state is indeed
      diamagnetic, since the EPR signal intensity steadily decreases without any line
      broadening as the temperature is lowered and becomes unobservable below about 50
      K. The signal is a single broad peak at all frequencies (90-370 GHz), ascribed to
      the thermally accessible excited states. Its g(iso) is 1.992 51, as expected for
      a high-spin Fe3+-containing species, and supports the chi data analysis.

PMID- 15859267
TI  - Cytochrome c-crown ether complexes as supramolecular catalysts: cold-active
      synzymes for asymmetric sulfoxide oxidation in methanol.
AB  - A series of supramolecular complexes of various cytochrome c proteins with 18
      crown-6 derivatives behave as cold-active synzymes in the H2O2 oxidation of
      racemic sulfoxides. This interesting behavior contrasts with native
      functionality, where the employed proteins act as electron transfer carriers. ESI
      MS. UV, CD, and Raman spectroscopic characterizations reveal that four or five 18
      crown-6 molecules strongly bind to the surface of the cytochrome c and also that
      nonnatural low-spin hexacoordinate heme structures are induced in methanol.
      Significantly, crown ether complexation can convert catalytically inactive
      biological forms to catalytically active artificial forms. Horse heart, pigeon
      breast, and yeast cytochromes c all stereoselectively oxidize (S)-isomers of
      methyl tolyl sulfoxide and related sulfoxides upon crown ether complexation.
      These supramolecular catalysts show the highest efficiency and enantiomer
      selectivity at -40 degrees C in the H202-dependent sulfoxide oxidation, while
      oxidative decomposition of the heme moieties predominantly occurs at room
      temperature. The oxidation reactivity of the employed sulfoxides is apparently
      related to steric constraints and electrochemical oxidation potentials of their
      S=O bonds. Among the cytochrome c complexes, yeast cytochrome c demonstrates the
      lowest catalytic activity and degradation reactivity. It has a significantly
      different protein sequence, suggesting that crown ether complexation effectively
      activates heme coordination but may additionally alter the native backbone
      structure. The proper combination of cytochrome c proteins, 18-crown-6 receptors,
      and external circumstances can be used to successfully generate "protein-based
      supramolecular catalysts" exhibiting nonbiological reactivities.

PMID- 15859268
TI  - Systematic investigation of the hydrothermal syntheses of Pr(III)-PDA (PDA =
      pyridine-2,6-dicarboxylate anion) metal-organic frameworks.
AB  - A series of novel two-dimensional (2D) and three-dimensional (3D) praseodymium
      coordination polymers, namely, {[Pr3(PDA)4(HPDA)(H2O)8] x 8H2O}n (2),
      {[Pr2(PDA)3(H2O)3] x H2O}n (3), {[Pr(PDA)(H2O)4] x ClO4}n (4), and {
      [Pr2(PDA)2(H2O)5SO4] x 2H2O}n (5) (PDA = pyridine-2,6-dicarboxylic anion), was
      designed and synthesized under hydrothermal conditions. Complexes 1-3 (chainlike
      polymer, {[Pr(PDA)(HPDA)(H2O)2] x 4H2O}n (1) was also obtained independently by
      us, although it has been reported recently by Ghosh et al.) were fabricated
      successfully by simply tuning the Pr/PDA ratio and exhibited various and
      intriguing topological structures from a 1D chain to a 3D network. While the
      synthetic strategy of 5 was triggered and further performed only after 1 was
      structurally characterized. The complexes were characterized by X-ray single
      crystal determination, spectroscopic, and variable-temperature magnetic
      susceptibility analyses. In complex 2 an unusual nanosized square motif as a
      building block constructed by eight Pr ions was further assembled into a highly
      ordered 2D grid compound. In complex 3 the decanuclear Pr metal-based structure
      as a repeat unit interpenetrated to form a novel 3D polymer. Complex 4 was a 3D
      network polymer fabricated through a hexanuclear Pr ring as a building block, and
      ClO4- anions as guests were trapped in the cavity. In complex 5 six Pr atoms, two
      SO4(2-) anions, and carboxylic oxygen bridges constructed an intriguing rectangle
      structure as a repeat unit in the grid to form a 2D coordination polymer in which
      the unique bi-bidentate coordination mode of SO4(2-) anion was observed.

PMID- 15859269
TI  - Hydrolytic protein cleavage mediated by unusual mononuclear copper(II) complexes:
      X-ray structures and solution studies.
AB  - The crystal structures and redox and UV-vis/EPR spectroscopic properties of two
      new mononuclear copper(II) complexes, [Cu(HL1)Cl2] (1) and [Cu(L1)Cl] (2),
      prepared through the reaction between copper(II) chloride and the ligand 2
      [(bis(pyridylmethyl)amino)methyl]-4-methyl-6-formylphenol (HL1) under distinct
      base conditions, are reported along with solution studies. Also, we demonstrate
      that these CuII complexes are able to cleave unactivated peptide bonds from
      bovine serum albumin (BSA) and the thermostable enzyme Taq DNA polymerase at
      micromolar concentration, under mild pH and temperature conditions. The cleavage
      activity seems to be specific with defined proteolytic fragments appearing after
      protein treatment. The location of the specific cleavage sites was tentatively
      assigned to solvent-accessible portions of the protein. These are two of the most
      active Cu(II) complexes described to date, since their cleavage activity is
      detected in minutes and evidence is here presented for a hydrolytic mechanism
      mediating protein cleavage by these complexes.

PMID- 15859270
TI  - Pentanuclear Ba(II) complex of a macrocyclic ligand.
AB  - We report here the first pentanuclear Ba(II) complex of a new tri-aza, tri-oxa
      macrocycle with two carboxymethyl "arms" pending from two N atoms, H2L2. The
      crystal structure corresponds to the formula
      [Ba5(H0.375L2)4(ClO4)(CH3CH2OH)(H2O)2](ClO4)2.5 x 9.5H2O and reveals the presence
      of four molecules of the ligand surrounding five Ba(II) ions, giving rise to an
      unusual structure with the metal ions inside a spherical organic cavity.

PMID- 15859271
TI  - K5(UO2)2[Si4O12(OH)]: a uranyl silicate containing chains of four silicate
      tetrahedra linked by SiO...HOSi hydrogen bonds.
AB  - A new uranium(VI) silicate, K5(UO2)2[Si4O12(OH)], has been synthesized by a high
      temperature, high-pressure hydrothermal method. It crystallizes in the
      orthorhombic space group Pbcm (No. 57) with a = 13.1274(7) A, b = 12.2635(7) A, c
      = 22.233(1) A, and Z= 8. Its structure consists of unbranched chains of four
      silicate tetrahedra extending along the b axis linked together via corner-sharing
      by UO6 tetragonal bipyramids to form a 3-D framework, which delimits intersecting
      channels along the c and b axes to accommodate K+ cations. A hydrogen atom is
      bonded to a terminal oxygen of a terminal silicate in the oligosilicate anion.
      Adjacent chains are linked along the b axis by hydrogen bonds. The sample shows a
      resonance at 14.7 ppm the 1H MAS NMR spectrum, which is assigned to the
      SiO...HOSi hydrogen bond. A comparison of uranyl silicate structures is made.

PMID- 15859272
TI  - Kinetics and mechanism of hydrolysis of a model phosphate diester by
      [Cu(Me3tacn)(OH2)2]2+ (Me3tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane).
AB  - The kinetics of hydrolysis of bis(p-nitrophenyl)phosphate (BNPP) by
      [Cu(Me3tacn)(OH2)2]2+ has been studied by spectrophotometrical monitoring of the
      release of the p-nitrophenylate ion from BNPP. The reaction was followed for up
      to 8000 min at constant BNPP concentration (15 microM) and ionic strength (0.15
      M) and variable concentration of complex (1.0-7.5 mM) and temperature (42.5-65.0
      degrees C). Biphasic kinetic traces were observed, indicating that the complex
      promotes the cleavage of BNPP to NPP [(p-nitrophenyl)phosphate] and then cleavage
      of the latter to phosphate, the two processes differing in rate by 50-100-fold.
      Analysis of the more amenable cleavage of BNPP revealed that the rate of BNPP
      cleavage is among the highest measured for mononuclear copper(II) complexes and
      is slightly higher than that reported for the close analogue
      [Cu(iPr3tacn)(OH2)2]2+. Detailed analysis required the determination of the pKa
      for [Cu(Me3tacn)(OH2)2]2+ and the constant for the dimerization of the conjugate
      base to [(Me3tacn)Cu(OH)2Cu(Me3tacn)]2+ (Kdim). Thermodynamic parameters derived
      from spectrophotometric pH titration and the analysis of the kinetic data were in
      reasonable agreement. Second-order rate constants for cleavage of BNPP by
      [Cu(Me3tacn)(OH2)(OH)]+ and associated activation parameters were obtained from
      initial rate analysis (k = 0.065 M(-1) s(-1) at 50.0 degrees C, deltaH = 56+/-6
      kJ mol(-1), deltaS = -95+/-18 J K(-1) mol(-1)) and biphasic kinetic analysis (k =
      0.14 M(-1) s(-1) at 50.0 degrees C, deltaH = 55+/-6 kJ mol(-1), deltaS = -92+/-20
      J K(-1) mol(-1)). The negative entropy of activation is consistent with a
      concerted mechanism with considerable associative character. The complex was
      found to catalyze the cleavage of BNPP with turnover rates of up to 1 per day.
      Although these turnover rates can be considered low from an application point of
      view, the ability of the complexes to catalyze phosphate ester cleavage is
      clearly demonstrated.

PMID- 15859273
TI  - Single-source approach to cubic FeS2 crystallites and their optical and
      electrochemical properties.
AB  - Cubic FeS2 crystallites have been synthesized via a single-source approach using
      iron diethyldithiocarbamate as precursor under hydrothermal conditions. The
      sample is characterized by XRD, IR, TEM, and FESEM. The optical properties of the
      as-prepared FeS2 reveal that there exists a red shift compared with that of bulk
      materials. Meanwhile, the electrochemical properties of FeS2 demonstrate that it
      delivers a large discharge capacity, which might find possible application as an
      electrode material in lithium cells. It is also found that the reaction
      temperature is of importance to the formation of cubic FeS2 crystallites.

PMID- 15859274
TI  - Di([5]trovacenyl)ethyne, di([5]trovacenyl)butadiyne, and di-1,4
      ([5]trovacenylethynyl)benzene: electrocommunication and magnetocommunication
      mediated by --C triple bond C--, --C triple bond C--C triple bond C-- and --C
      triple bond C--C6H4--C triple bond C-- spacers.
AB  - The synthesis of dinuclear derivatives of trovacene (eta7-C7H7)V(eta5-C5H5) (1.)
      is reported, in which ethynyl (6..), butadiynyl (7..), and 1,4-di(ethynyl)phenyl
      (8..) groups serve as spacers between paramagnetic (S = 1/2) [5]trovacenyl units.
      The mononuclear precursors [5]trovacenylcarbaldehyde (2.) and
      [5]trovacenylacetylene (4.) are also described. Structural characterization by X
      ray diffraction has been performed for 4., 6.., 7.., and 8.. Electronic
      communication as gleaned from cyclic voltammetry only manifests itself in the
      reduction processes where redox splitting deltaE1/2(0/ 1-, 1-/2-) is resolved for
      6.. (deltaE1/2 = 150 mV) and indicated for 7.. (deltaE1/2 < or approximately 80
      mV). Magnetocommunication leads to exchange coupling of the two electron spins
      which reside in vanadium centered orbitals. The values JEPR(6..) = (-)0.92,
      JEPR(7..) = (-)0.56, and JEPR(8..) = (-)0.005 cm(-1) are derived from the 51V
      hyperfine patterns. Accordingly, attenuation of exchange interaction by
      oligoalkyne spacers is weak, corresponding to a factor of 0.6 only per added --C
      triple bond C-- unit. In the determination of very weak long distance exchange
      interactions, EPR excels because of the range 5 x 10(-4) < or approximately J <
      or approximately 1.5 cm(-1) accessible in the case of 51V as a reporting magnetic
      nucleus and because competing intermolecular exchange is quenched in dilute fluid
      solution. This is demonstrated by the value Jchi(7..) = -3.84 cm(-1) obtained
      from a magnetic susceptibility study, which exceeds JEPR(7..) by a factor of 7.
      The small magnitude of spin exchange interaction between trovacene units reflects
      the fact that the spin bearing V3dz2 orbital is virtually orthogonal to the pi
      perimeter ligand orbitals and weakly overlapping only with the a1g(sigma) ring
      orbitals, creating two bottlenecks for spin-exchange in the spacer-containing
      ditrovacenes.

PMID- 15859275
TI  - Effect of crystal packing on the structures of polymeric metallocenes.
AB  - The pressure dependencies of the crystal structures of the polymeric metallocenes
      lithium cyclopentadienide (LiCp) and potassium cyclopentadienide (KCp) have been
      determined by synchrotron X-ray powder diffraction. The decrease of the volume of
      LiCp by 34% up to a pressure of p = 12.2 GPa and of KCp by 23% at p = 5.3 GPa as
      well as the bulk moduli of K = 7.7 GPa for LiCp and 4.9 GPa for KCp indicate a
      high compressibility for these compounds. The crystal structures of KCp have been
      determined up to p = 3.9 GPa. An increase of the bend angle is found from 45
      degrees at p = 0 GPa up to 51 degrees at p = 3.9 GPa. This variation is
      completely explained by a model invoking attractive K+ Cp- interaction and
      repulsive nonbonded carbon-carbon interactions. It is proposed that the bend
      angle in the polymeric alkali metal metallocenes is the result of the
      optimization of the crystal packing.

PMID- 15859276
TI  - Cyano-bridged structures based on [MnIIN3O2-macrocycle)]2+: a synthetic,
      structural, and magnetic study.
AB  - Reactions between the complex [MnII(L)]2+, where L is a N3O2 macrocyclic ligand,
      and different cyanometalate precursors such as [M(CN)n]m- (M(III) = Cr, Fe; M(II)
      = Fe, Ni, Pd, Pt) lead to cyano-bridged molecular assemblies exhibiting a variety
      of structural topologies. The reaction between [MnII(L)]2+ and [FeII(CN)6]4-
      forms a trinuclear complex with formula [(MnII(L)(H2O))2(FeII(micro-CN)2(CN)4)] x
      2MeOH x 10H2O (1) which crystallizes in the triclinic space group P1. The
      reaction between [MnII(L)]2+ and [M(II)(CN)4]2-, where M(II) = Ni (2), Pd (3), Pt
      (4), gives rise to three isostructural linear chain compounds with stoichiometry
      [(MnII(L))(M(II)(micro-CN)2(CN)2)]n and which crystallize in the monoclinic space
      group C2/c. The self-assembly between [MnII(L)]2+ with [M(III)(CN)6]3-, where
      M(III) = Cr (5), Fe (6, 7, 8), forms three types of compounds. Compounds 5 and 6
      are isostructural (monoclinic, space group P2(1)/n), and the structures comprise
      anionic linear chains [(MnII(L))(M(III)(micro-CN)2(CN)4)]n(n-) with cationic
      trinuclear complexes [(MnII(L)(H2O))2(M(III)(micro-CN)2(CN)4)]+ as counterions.
      Using an excess of K3[FeIII(CN)6], an analogous compound to 6 but with K+ as
      counterion is obtained (7), which crystallizes in the triclinic space group P1.
      Compound 8 consists of 2-D layers with formula [(MnII(L))3(FeIII(micro
      CN)4(CN)2)(FeIII(micro-CN)2(CN)4)]n x 2nMeOH; it crystallizes in the monoclinic
      space group P2(1)/n. The magnetic properties were investigated for all samples.
      In particular, compound 5, which shows antiferromagnetic exchange interactions
      between Mn(II) and Cr(III) ions through cyanide bridging ligands, has been
      studied in detail; the magnetic exchange parameter amounts to J = -7.5(7) cm(-1).
      Compound 8 shows a magnetically ordered phase below 6.4 K which is confirmed by
      Mossbauer spectroscopy; two hyperfine split spectra were observed below Tc from
      which IJI values of 2.1 and 1.6 cm(-1) could be deduced.

PMID- 15859277
TI  - Formation of CH3TiX, CH2=TiHX, and (CH3)2TiX2 by reaction of methyl chloride and
      bromide with laser-ablated titanium atoms: photoreversible alpha-hydrogen
      migration.
AB  - The simple methylidene (CH2=TiHX) and Grignard-type (CH3TiX) complexes are
      produced by reaction of methyl chloride and bromide with laser-ablated Ti atoms
      and isolated in a solid Ar matrix, and they form a persistent photoreversible
      system via alpha-hydrogen migration between the carbon and titanium atoms. The
      Grignard-type product is transformed to the methylidene complex upon UV (240 nm <
      lambda < 380 nm) irradiation and vice versa with visible (lambda > 530 nm)
      irradiation. More stable dimethyl dihalide complexes [(CH3)2TiX2] are also
      identified, whose relative concentration increases upon annealing and at high
      methyl halide concentration. The reaction products are identified with three
      different groups of absorptions on the basis of the behaviors upon broadband
      photolysis and annealing, and the vibrational characteristics are in a good
      agreement with DFT computation results.

PMID- 15859278
TI  - Cu(HCO2)2(pym) (pym = pyrimidine): low-dimensional magnetic behavior and long
      range ordering in a quantum-spin lattice.
AB  - We synthesized and structurally and magnetically characterized the novel 3D
      coordination polymer Cu(HCO2)2(pym) (pym = pyrimidine). The compound crystallizes
      in the monoclinic space group C2/c with a = 14.4639(8) A, b = 7.7209(4) A, c =
      8.5172(5) A, beta = 126.076(2) degrees, and V= 768.76(7) A3. In the structure
      buckled layers of Cu(HCO2)2 are interconnected by pym ligands to afford 1D Cu-pym
      Cu chains. Bulk magnetic susceptibility measurements show a broad maximum at 25 K
      that is indicative of short-range magnetic ordering. Between 12 and 300 K a least
      squares fit of the chi(T) data to a mean-field-corrected antiferromagnetic chain
      model yielded excellent agreement for g = 2.224(3), J/kB = -26.9(2) K, and zJ'/kB
      = -1.1(3) K. Below approximately 3 K a transition to long-range magnetic ordering
      is observed, as suggested by a sharp and sudden decrease in chi(T). This result
      is corroborated by muon spin relaxation measurements that show oscillations in
      the muon asymmetry below T(N) = 2.802(1) K and rapidly fluctuating moments above
      T(N).

PMID- 15859279
TI  - Anion-dependent silver(I) coordination polymers of the tridentate
      pyridylphosphonite: PPh(3-OCH2C5H4N)2.
AB  - Three new multidimensional coordination polymers have been constructed from the
      reaction of AgX, where X = OTf-, BF4-, or tfa-, with the novel phosphonite PhP(3
      OCH2C5H4N)2, PCP-32, 1. It is seen that regardless of the ratio of reactants
      mixed, polymeric growth of the compounds always reveals a ligand-to-metal ratio
      of 1:2 for PCP-32AgOTf, 2, 1:1 for PCP-32AgBF4, 3, and 1:2 for PCP-32Ag(tfa), 4.
      The coordination number, metal environment, ligand conformation, and polymer
      dimensionality are found to vary greatly from 2 to 4 and are dependent upon the
      anion present. Coordination numbers from 2 to 4, representing linear, trigonal,
      and distorted tetrahedral environments are displayed. PCP-32AgOTf polymerizes as
      a linear chain containing both two- and four-coordinate silvers, PCP-32AgBF4
      repeats a single trigonal motif throughout its structure, and PCP-32Ag(tfa) shows
      two unique distorted tetrahedral silver centers. Ligand flexibility allows for
      cross-ligand Ag-Ag distances to range from 3.1918(8) to 14.015(2) A. The
      coordination polymers have been characterized by elemental analysis, variable
      temperature multinuclear NMR spectroscopy, single-crystal X-ray diffraction, and
      fluorometric studies.

PMID- 15859280
TI  - Thermodynamic profiles for CO photodissociation from heme model compounds: effect
      of proximal ligands.
AB  - Here we present a comprehensive study of the thermodynamic parameters (enthalpy,
      entropy, and volume changes) associated with carbon monoxide photodissociation
      and rebinding to Fe(II) microperoxidase-11 (Fe(II)MP11) and Fe(ll) tetrakis(4
      sulfonatophenyl)porphine complex (FeII4SP) with water and 2-methylimidazole as
      proximal ligands. CO photodissociation from FeII4SP complexes is accompanied by a
      positive volume change of approximately 17 mL mol(-1). A smaller volume change of
      approximately 12 mL mol(-1) was observed for CO dissociation from Fe(II)MP-11. We
      attribute the positive volume change to cleavage of the Fe-CO covalent bond and
      to solvent reorganization due to the low-spin to high-spin transition. CO binding
      is an exothermic reaction with an enthalpy change of -17 kcal mol(-1) for the CO
      FeII4SP complexes and -13 kcal mol(-1) for the CO-Fe(II)MP11 complex. In all
      cases, the ligand recombination occurs as a single-exponential process indicating
      that CO dissociation is followed by direct CO rebinding to a high-spin five
      coordinate complex without concomitant dissociation of the proximal base. In
      addition, observed negative activation entropies and volumes for ligand binding
      to (2-Melm)FeII4SP and MP-11, respectively, suggest that CO rebinding can be
      described by an associative mechanism with bond formation being the rate-limiting
      step.

PMID- 15859281
TI  - Tetracyanoborate salts M[b(CN)4] with M = singly charged cations: properties and
      structures.
AB  - A series of tetracyanoborate salts M[B(CN)4] with the singly charged cations of
      Li+, Na+, Rb+, Cs+, [NH4]+, Tl+, and Cu+ as well as the THF solvate
      tetracyanoborates Na[B(CN)4] x THF and [NH4][B(CN)4] x THF were synthesized and
      their X-ray structures, vibrational spectra, solubilities in water, and thermal
      stabilities determined and compared with already known M[B(CN)4] salts.
      Crystallographic data for these compounds are as follows: Na[B(CN)4], cubic,
      Fd3m, a = 11.680(1) A, Z= 8; Li[B(CN)4], cubic, P43m, a = 5.4815(1) A, Z= 1;
      Cu[B(CN)4], cubic, P43m, a = 5.4314(7) A, Z= 1; Rb[B(CN)4], tetragonal, /4(1)/a,
      a = 7.1354(2) A, c= 14.8197(6) A, Z= 4; Cs[B(CN)4], tetragonal, /4(1)/a, a =
      7.300(2) A, c = 15.340(5) A, Z= 4; [NH4][B(CN)4], tetragonal, /4(1)/a, a =
      7.132(1) A, c = 14.745(4) A, Z= 4; Tl[B(CN)4], tetragonal, /4(1)/a, a = 7.0655(2)
      A, c = 14.6791(4) A, Z= 4; Na[B(CN)4] x THF, orthorhombic, Pnma, a = 13.908(3) A,
      b = 9.288(1) A, c = 8.738(1) A, Z= 4; [NH4][B(CN)4] x THF, orthorhombic, Pnma, a
      = 8.831(1) A, b = 9.366(2) A, c = 15.061(3) A, Z= 4. The cubic Li+, Na+, and Cu+
      salts crystallize in a structure consisting of two interpenetrating independent
      tetrahedral networks of M cations and [B(CN)4]- ions. The compounds with the
      larger countercations (Rb+, Cs+, Tl+, and [NH4]+) crystallize as tetragonal, also
      with a network arrangement. The sodium and ammonium salts with the cocrystallized
      THF molecules are both orthorhombic but are not isostructural. In the vibrational
      spectra the two CN stretching modes A1 and T2 coincide in general and the band
      positions are a measure for the strength of the interionic interaction. An
      interesting feature in the Raman spectrum of the copper salt is the first
      appearance of two CN stretching modes.

PMID- 15859282
TI  - Formation of hypervalent complexes of trifluorosilanes with pyridine and with 4
      methoxypyridine, through intermolecular silicon...nitrogen interactions.
AB  - Herein we report that trifluorohexylsilane (2), trifluorophenylsilane (3) and
      trifluoro(pentafluorophenyl)silane (4) form new hypervalent complexes with
      pyridine (py) and with 4-methoxypyridine (MeO-py), through intermolecular Si...N
      interactions. In general, stronger and more efficient binding is observed for the
      more electron poor (Si atom in) silane 4 and for the more electron rich (N atom
      in) 4-methoxypyridine. Binding constants of 15+/-2, 25+/-5, and 550+/-100 M(-1)
      at 25 degrees C in benzene were measured for the formation of the pentacoordinate
      2.py, 3.py, and 3.MeO-py complexes, respectively. In addition, silane 3 also
      forms the hexacoordinate 3-2py and 3-2MeO-py complexes at low temperatures and
      silane 4 forms the 4-2py complex below room temperature and the 4-2MeO-py complex
      already at room temperature and in a high concentration. The various types of
      hypervalent complexes and different binding strengths described here for silanes
      2-4 and previously for trifluoro(phenylethynyl)silane (1) and the possibility to
      modulate the binding modes (penta- vs hexacoordination) of these complexes (by
      the type of amine used, concentration, and the temperature applied) suggest that
      such new intermolecular Si...N interactions could be used as efficient and
      versatile binding motifs in supramolecular chemistry.

PMID- 15859283
TI  - Silver(I) coordination polymers of fluorescent oligo(phenylenevinylene) with pi
      pi stackings: luminescence and conductivity.
AB  - Three luminescent silver(I)-oligo(phenylenevinylene) complexes,
      [Ag2(bmsb)(ClO4)2] (1), [Ag2(bmsb)(H2O)4](BF4)2 (2), and [Ag2(bdb)(CF3SO3)2] (3)
      (bmsb = 1, 4-bis(methylstyryl)benzene, bdb = 4,4'-bis(2, 5
      dimethylstryryl)biphenyl), have been synthesized and structurally characterized.
      Complexes 1 and 2 are 2D networks with unique metallocyclophane motifs. Complex 3
      affords a 2D zigzag sheet, in which silver triflates form tubelike double chains
      and bdb molecules act as linkages. Complex 2 exhibits high electric conductivity
      because of columnar aromatic stackings formed through intra- and intermolecular
      pi-pi interactions. Complexes 1-3 in the solid state exhibit luminescence, of
      which excitation and emission maxima are shifted to longer wavelength as compared
      to those of the corresponding metal-free ligands.

PMID- 15859284
TI  - Syntheses and characterization of oxo-centered triruthenium compounds with
      orthometalated bipyridine.
AB  - Reaction of oxo-centered triruthenium precursor compound
      [Ru3O(OAc)6(py)2(CH3OH)](PF6) (1) with 1.3 equiv of bipyridine ligand at ambient
      temperature gave oxo-centered triruthenium derivatives [Ru3O(OAc)5{micro
      eta1(C),eta2(N,N)bipyridine}(py)2](PF6) (bipyridine = 4,4'-dibutyl-2,2'
      bipyridine (dbbpy) (2),4,4'-dimethyl-2,2'-bipyridine (dmbpy) (3), 2,2'-bipyridine
      (bpy) (4), 5,5'-dibromo-2,2'-bipyridine (Br2bpy) (5), 1,10-phenanthroline (phen)
      (6)). Formation of compounds 2-6 involved substitution of the axial methanol and
      one of bridging acetates in the precursor compound 1 by an orthometalated
      bipyridine. Reduction of 2 and 4 by addition of excess hydrazine gave one
      electron-reduced neutral products Ru3O(OAc)5(py)2{micro-eta1 (C),eta2(N,N)
      bipyridine} (bipyridine = dbbpy (2a), bpy (4a)). As established in the structure
      of 3 by X-ray crystallography, the orthometalated 2,2'-bipyridine adopts a micro
      eta1(C),eta2(N,N) bonding mode. In the 1H NMR spectra of 2-6, the protons of
      acetate, pyridine, and bipyridine show obvious paramagnetic shifts. Tentative
      assignments of these proton signals were carried out. Absorption spectra of the
      bipyridine triruthenium derivatives show characteristic intracluster charge
      transfer (IC) transitions in the visible to near-infrared region (600-1000 nm)
      and cluster-to-ligand charge transfer (CLCT) transitions at 320-450 nm. By
      comparison of the redox data for 2-6, it is concluded that introducing electron
      donating substituents to the bipyridine favors stabilizing the [RuIII3]+ and
      [RuIII2RuII]0 states against disproportionation.

PMID- 15859286
TI  - Rhenium chemistry of azooximes: oxygen atom transfer, azoimine chelation, and
      imine-oxime contrast.
AB  - The concerned azooximes (L1OH, 1) are of type p-X-C6H4C(N2Ph)(NOH) (X = H, Me,
      Cl). The reaction of [Re(MeCN)Cl3(PPh3)2] with [Ag(L1OH)(L1O)] in cold
      dichloromethane-acetonitrile solvent has furnished the green colored ionized
      azoimine complex [ReV(O)Cl(PPh3)2(L1)](PF6), 2. In effect L1O- has undergone
      oxidative addition, the oxygen atom being transferred to the metal site. Upon
      treatment of [ReV(NPh)Cl3(PPh3)2] with L1OH in solution, the neutral azoimine
      complex [ReV(NPh)Cl3(L1H)], 3, resulted due to the spontaneous transfer of the
      oxime oxygen atom to a PPh3 ligand, which is eliminated as OPPh3. In contrast,
      the oxime of 2-acetylpyridine (L2OH, 4) did not undergo oxygen atom transfer and
      simply afforded the imine-oxime complex [ReV(NC6H4Y)Cl2(PPh3)(L2O)], 5, upon
      reacting with [ReV(NC6H4Y)Cl3(PPh3)2] (Y = H, Me, Cl). The spectral and
      electrochemical properties of 2, 3, and 5 and the structures of three
      representative compounds are reported. In the cation of 2 (X = H) the two PPh3
      ligands lie trans to each other and the equatorial plane is defined by the five
      membered azoimine chelate ring and the oxo and chloro ligands. The oxo ligand
      which forms a model triple bond (Re-O length 1.616(6) A) lies cis to the imine-N
      atom. In 3 (X = Cl) the ReCl3 fragment has meridional geometry and the imido
      nitrogen lies trans to the imine nitrogen of the planar azoimine chelate ring. In
      5 x H2O (Y = Me), the Cl, oximato-N, and P atoms define an equatorial plane and
      the pyridine-N lies trans to the imido-N. The water of crystallization is
      hydrogen bonded to the oximato oxygen atom (O...O, 2.829(5) A). Reaction models
      in which chelation of the azooxime precedes oxygen atom transfer are proposed on
      the basis of oxophilicity of trivalent rhenium, Lewis acid activity of
      pentavalent rhenium, electron withdrawal by the azo group, and observed relative
      disposition of ligands in products.

PMID- 15859285
TI  - Chromium(V) peptide complexes: synthesis and spectroscopic characterization.
AB  - A series of stable Cr(V) model complexes that mimic the binding of Cr(V) to
      peptide backbones at the C-terminus of proteins have been prepared for N,N
      dimethylurea derivatives of the tripeptides Aib3-DMF, AibLAlaAib-DMF, and
      AibDAlaAib-DMF (Aib = 2-amino-2-methylpropanoic acid, DMF = N,N
      dimethylformamide). The Cr(ll) precursor complexes were synthesized by the
      initial deprotonation of the amide and acid groups of the peptide ligands in DMF
      with potassium tert-butoxide in the presence of CrCl2. The Cr(II) intermediates
      thus formed were then immediately oxidized to Cr(V) using tert-butyl
      hydroperoxide. Spectroscopic and mass-spectrometric analyses of the Cr(V)
      complexes showed that a new metal-directed organic transformation of the ligand
      had occurred. This involved a DMF solvent molecule becoming covalently bound to
      the amine group of the peptide ligand, yielding a urea group, and a third
      coordinated deprotonated urea nitrogen donor. A metal-directed oxidative coupling
      has been proposed as a possible mechanism for the organic transformation. The
      Cr(V/IV) reduction potential was determined for the three Cr(V) complexes using
      cyclic voltammetry, and in all cases it was quasi-reversible. These are the first
      isolated and fully characterized Cr(V) complexes with non-sulfur-containing
      peptide ligands.

PMID- 15859287
TI  - Cations M2(O2CtBu)4+, where M = Mo and W, and MoW(O2CtBu)4+. Theoretical,
      spectroscopic, and structural investigations.
AB  - With the aid of density function theory, the molecular and electronic structures
      of the molecules Mo2(O2CMe)4, MoW(O2CMe)4, and W2(O2CMe)4 and their single
      electron oxidized radical cations have been determined; this includes calculated
      observables such as v(MM) and the delta --> delta* electronic transition
      energies. The calculated properties are compared with those for the corresponding
      pivalates, M2(O2CtBu)4 (M = Mo or W) and MoW(O2CtBu)4 and their radical cations
      prepared in situ by oxidation with Cp2FePF6. The EPR spectra of the radical
      cations are also reported. The EPR spectrum of the MoW(O2CtBu)4+ cation reveals
      that the unpaired electron is in a polarized MM delta orbital having 70% Mo and
      30% W character. The MM stretching frequencies show good correlation with the MM
      bond lengths obtained from single-crystal X-ray diffraction studies of
      MoW(O2CtBu)4, W2(O2CtBu)4, and W2(O2CtBu)4+PF6- compounds, along with previously
      reported structures. These data provide benchmark parameters for valence trapped
      dicarboxylate bridged radical cations of the type [(tBuCO2)3M2]2(micro-O2C-X
      CO2)+ (X = conjugated spacer).

PMID- 15859288
TI  - Reaction systems related to dissimilatory nitrate reductase: nitrate reduction
      mediated by bis(dithiolene)tungsten complexes.
AB  - Kinetics of the oxygen atom transfer reactions [M(IV)(QC6H2-2,4,6
      Pr(i)3)(S2C2Me2)2]1- + XO --> [M(VI)O(QC6H2-2,4,6-Pr(i)3)(S2C2Me2)2]1- + X in
      acetonitrile with substrates XO = NO3- and (CH2)4SO have been determined. The
      reactants are bis(dithiolene) complexes with M = Mo, W and sterically encumbered
      axial ligands with Q = O, S to stabilize mononuclear square pyramidal structures.
      The complex [MoIV(SC6H2-2,4,6-Pr(i)3)(S2C2Me2)2]1- is an analogue of the active
      site of dissimilatory nitrate reductase which in the reduced state contains a
      molybdenum atom bound by two pyranopterindithiolene ligands and a cysteinate
      residue. Nitrate reduction was studied with tungsten complexes because of
      unfavorable stability properties of the molybdenum complexes. Product nitrite was
      detected by a colorimetric method. All reactions with both substrates are second
      order with associative transition states (deltaS approximately -20 eu). Variation
      of atoms M and Q, together with data from prior work, allows certain kinetics
      comparisons to be made. Among them, k2W/k2Mo = 25 for (CH2)4SO reduction (Q = S),
      an expression of the kinetic metal effect. Further, k2S/k2O = 28 and
      approximately 10(4) for nitrate and (CH2)4SO reduction, respectively, effects
      attributed to relatively more steric congestion in achieving the transition state
      with hindered phenolate vs thiolate ligands. The effect is more pronounced with
      the larger substrate. These results demonstrate the feasibility of tungsten
      mediated nitrate reduction by direct atom transfer using molecules with both
      axial thiolate and phenolate ligands. Complexes of the type [M(IV)(OR)(S2C2Me2)2]
      are capable of reducing biological N-oxide, S-oxide, and nitrate substrates and
      thus constitute functional analogue reaction systems of enzymic transformations.

PMID- 15859289
TI  - Conducting polymers containing in-chain metal centers: electropolymerization of
      oligothienyl-substituted {M(tpy)2} complexes and in situ conductivity studies, M
      = Os(II), Ru(II).
AB  - The electropolymerization of a series of Ru and Os bis-terpyridine complexes that
      form rodlike polymers with bithienyl, quaterthienyl, or hexathienyl bridges has
      been studied. Absorption spectroscopy, scanning electron microscopy, and cyclic
      voltammetry have been used to characterize the monomers and resulting polymer
      films. The absolute dc conductivity of the quaterthienyl-bridged {Ru(tpy)2} and
      {Os(tpy)2} polymers is unusually large and independent of the identity of the
      metal center at 1.6 x 10(-3) S cm(-1). The maximum conductivity occurs at the
      formal potential of each redox process, which typically is observed for systems
      where redox conduction is the dominant charge transport mechanism. Significantly,
      the dc conductivity of the metal-based redox couple observed in these polymers is
      2 orders of magnitude higher thanthat of a comparable nonconjugated system.

PMID- 15859290
TI  - Interaction of molybdocene dichloride with cysteine-containing peptides:
      coordination, regioselective hydrolysis, and intramolecular aminolysis.
AB  - Reactions of the organometallic compound molybdocene dichloride (Cp2MoCl2, Cp =
      eta5-cyclopentadienyl) with the cysteine-containing peptides L-cysteinylglycine
      (Cys-Gly), N-acetyl-L-cysteine (AcCys), glycyl-L-cysteine (Gly-Cys), glycyl-L
      cysteinylglycine (Gly-Cys-Gly), and gamma-L-glutamyl-L-cysteinylglycine
      (glutathione, GSH) have been studied in aqueous solution in the pH range 2-9. The
      dipeptides Cys-Gly and Gly-Cys and the acetylated amino acid AcCys form 1:1 and
      2:1 complexes of composition [Cp2Mo(peptide-S)(OH(2))]n+/- and [Cp2Mo(peptide
      S)2]n+/- as well as the chelates [Cp2Mo(AcCys-S,O)], [Cp2Mo(Gly-Cys-S,O)]+, and
      [Cp2Mo(Cys-Gly-S,N)] with the Cp2Mo2+ unit binding to the deprotonated thiolate
      group and the free amino or carboxylate group of the cysteine residue. Upon
      treatment of Gly-Cys-Gly and the naturally occurring tripeptide GSH with Cp2MoCl2
      at elevated temperature, release of free glycine was observed. The Cp2Mo2+ entity
      coordinates to the thiolate group of GSH and mediates regioselective hydrolysis
      of the Cys-Gly peptide bond by intramolecular metal hydroxide activation. Cp2Mo2+
      promoted hydrolysis of GSH was followed at pD 7.4 and 5.2 and 40 and 60 degrees
      C. By contrast, the Cys-Gly bond in [Cp2Mo(Gly-Cys-Gly-S,N)] is cleaved by
      intramolecular aminolysis at pD > or = 7.4 and 60 degrees C leading to glycine
      and the Cp2Mo2+ complex of the 2,5-diketopiperazine derivative cyclo-(Gly-Cys).
      Chelating coordination of the Cp2Mo2+ moiety to the thiolate group and to the
      deprotonated amide nitrogen of the tripeptide changes the configuration of the
      peptide bond from (preferred) trans to cis, thus enabling nucleophilic attack of
      the primary amino group at the Cys-Gly bond. The reaction product [Cp2Mo{cyclo
      (Gly-Cys)}] x 2H2O has been characterized by X-ray crystallography.

PMID- 15859291
TI  - Hydride affinities of borane derivatives: novel approach in determining the
      origin of lewis acidity based on triadic formula.
AB  - The problem of intrinsic Lewis acidities of simple boron compounds (BH3-mXm, m =
      0-3, X = F, Cl, Br, CH3, and OH) is assessed by their gas-phase hydride
      affinities (HAs). A simple and intuitively appealing picture of the interaction
      process including detachment of an electron from the hydride ion H-, capture of
      the pruned electron to the investigated Lewis acid (LA), and subsequent formation
      of the homolytic chemical bond between two newly created radicals is proposed. It
      enables transparent and straightforward dissection of the initial and final state
      effects, which taken together with the intermediate relaxation stabilization
      determine the trend of changes in the hydride affinities. The former effect is
      reflected in the electron affinities of the neutral Lewis acids given within
      Koopmans' approximation, while the final state effect involves properties of the
      formed Lewis acid-base adducts mirrored in the bond dissociation energy of the
      formed [LA-H]- chemical bond. It is demonstrated that unexpectedly low Lewis
      acidity of fluoroboranes relative to the corresponding chlorine and bromine
      derivatives can be traced down to the unfavorable Koopmans' electron affinities.
      Hence, it is a consequence of the initial state effect. In contrast,
      chloroboranes are more potent Lewis acids than fluoroboranes, because the
      relaxation and final state effects decisively influence their Lewis acidity.
      Finally, bromine-substituted borane compounds provide the most powerful studied
      Lewis acids. Their hydride affinities are result of a synergic interplay of the
      initial state, intermediate stabilization via relaxation, and final state
      effects. It is shown that Pearson's global hardness indices defined within his
      hard and soft acid-base (HSAB) principle fail to adequately predict and interpret
      the calculated hydride affinities.

PMID- 15859292
TI  - Studies relevant to catalytic reduction of dinitrogen to ammonia by molybdenum
      triamidoamine complexes.
AB  - In this paper we explore several issues surrounding the catalytic reduction of
      dinitrogen by molybdenum compounds that contain the [(HIPTNCH2CH2)3N]3- ligand
      (where HIPT = 3,5-(2,4,6-i-Pr3C6H2)2C6H3). Four additional plausible
      intermediates in the catalytic dinitrogen reduction have now been
      crystallographically characterized; they are MoN= NH (Mo = [(HIPTNCH2CH2)3N]Mo),
      [Mo=NNH2][BAr'4] (Ar' = 3,5-(CF3)2C6H3), [Mo=NH][BAr'4], and Mo(NH3). We also
      have crystallographically characterized a 2,6-lutidine complex, Mo(2,6-Lut)+,
      which is formed upon treatment of MoH with [2,6-LutH][B(C6F5)4]. We focus on the
      synthesis of compounds that have not yet been isolated, which include Mo=NNH2,
      Mo=NH, and Mo(NH2). Mo=NNH2, formed by reduction of [Mo=NNH2]+, has not been
      observed. It decomposes to give mixtures that contain two or more of the
      following: MoN=NH, Mo triple bond N, Mo(NH3)+, Mo(NH3), and ammonia. Mo=NH, which
      can be prepared by reduction of [Mo=NH]+, is stable for long periods in the
      presence of a small amount of CrCp*2, but in the absence of CrCp*2, and in the
      presence of Mo=NH+ as a catalyst, Mo=NH is slowly converted into a mixture of Mo
      triple bond N and Mo(NH2). Mo(NH2) can be produced independently by deprotonation
      of Mo(NH3)+ with LiN(SiMe3)2 in THF, but it decomposes to Mo triple bond N upon
      attempted isolation. Although catalytic reduction of dinitrogen could involve up
      to 14 intermediates in a "linear" sequence that involves addition of "external"
      protons and/or electrons, it seems likely now that several of these
      intermediates, along with ammonia and/or dihydrogen, can be produced in several
      reactions between intermediates that themselves behave as proton and/or electron
      sources.

PMID- 15859293
TI  - Utilization of CS2 as a source of C1 synthetic units for the preparation of
      bis(alkylthio)methanes and alkyl dithioformates.
AB  - Double insertion of CS2 into two Ru-H bonds of [(dppm)2Ru(H)2] (dppm =
      Ph2PCH2PPh2) affords the methanedithiolate complex [(dppm)2Ru(eta2-S2CH2)]. The
      methanedithiolate moiety has been functionalized using 2 equiv of RX resulting in
      bis(alkylthio)methane derivatives [(dppm)2Ru(RSCH2SR)][X]2. The
      bis(alkylthio)methane complex loses the bis(alkylthio)methane moiety under very
      mild conditions and in turn affords the [(dppm)2RuX2] complex from which the
      starting dihydride [(dppm)2Ru(H)2] has been regenerated via reaction with
      KOH/EtOH. On the other hand, insertion of CS2 into one Ru-H bond of
      [(dppe)2Ru(H)2] (dppe = Ph2PCH2CH2PPh2) followed by functionalization using RX
      results in alkyl dithioformate complex trans-[(dppe)2Ru(H)(SC(SR)H)][X]. In this
      case also, the alkyl dithioformate moiety gets eliminated under very mild
      conditions to afford the [(dppe)2Ru(H)(X)] derivative from which the starting
      dihydride has been regenerated via reaction with NaBH4. The reactions presented
      here constitute utilization of CS2 as a C1 synthetic source for the generation of
      useful organic compounds.

PMID- 15859294
TI  - Disilver(I) macrocycles: variation of cavity size with anion binding.
AB  - Reaction of the N-methylated bis(amidopyridine) ligand, LL = C6H4(1,3-CONMe-4
      C5H4N)2, with the silver salts AgNO3, AgO2CCF3, AgO3SCF3, AgBF4, and AgPF6 gave
      the corresponding cationic disilver(I) macrocycles [Ag2(micro-LL)2]X2, 2a-e. The
      transannular silver...silver distance in the macrocycles varies greatly from 2.99
      to 7.03 A, and these differences arise through a combination of different modes
      ofanion binding and from the presence or absence of silver...silver secondary
      bonding. In all complexes, the ligand adopts a conformation in which the methyl
      group and oxygen atom of the MeNCO units are mutually cis, but the overall
      macrocycle can exist in either boat (X = PF6 only) or chair conformation. Short
      transannular silver...silver distances are found in complexes 2b,c, in which the
      anions CF3CO2- and CF3SO3- bind above and below the macrocycle, but longer
      silver...silver distances are found for 2a,d,e, in which the anions are present,
      at least in part, inside the disilver macrocycle. Easy anion exchange occurs in
      solution, and studies using ESI-MS indicate that the anion binding to form
      [Ag2X(micro-LL)2]+ follows the sequence X = CF3CO2- > NO3- > CF3SO3-.

PMID- 15859295
TI  - Preparation and properties of the full series of cuboidal clusters [Mo(x)W4
      xSe4(H2O)12]n+ (n = 4-6) and their derivatives.
AB  - Hydrothermal reactions between incomplete cuboidal cluster aqua complexes
      [M3Q4(H2O)9]4+ and M(CO)6 (M = Mo, W; Q = S, Se) offer easy access to the
      corresponding cuboidal clusters M4Q4. The complete series of homometal and mixed
      Mo/W clusters [Mo(x)W4-xQ4(H2O)12]n+ (x = 0-4, n = 4-6) has been prepared. Upon
      oxidation of the mixed-metal clusters, it is the W atom which is lost, allowing
      selective preparation of new trinuclear clusters [Mo2WSe4(H2O)9]4+ and
      [MoW2Se4(H2O)9]4+. The aqua complexes were converted by ligand exchange reactions
      into dithiophosphato and thiocyanato complexes, and crystal structures of
      [W4S4((EtO)2PS2)6], [MoW3S4((EtO)2PS2)6], [Mo4Se4((EtO)2PS2)6], [W4Se4((i
      PrO)2PS2)6], and (NH4)6[W4Se4(NCS)12]-4H20 were determined. Cyclic voltammetry
      was performed on [Mo(x)W4-xCO4(H2O)12]n+, showing reversible redox waves 6+/5+
      and 5+/4+. The lower oxidation states are more difficult to access as the number
      of W atoms increases. The [Mo2WSe4(H2O)9]4+ and [MoW2Se4(H2O)9]4+ species were
      derivatized into [Mo2WSe4(acac)3(py)3]+ and [MoW2Se4(acac)3(py)3]+, which were
      also studied by CV. When appropriate, the products were also characterized by FAB
      MS and NMR (31P, 1H) data.

PMID- 15859296
TI  - New efficient synthesis of [Ul4(meCN)4]. X-ray crystal structures of
      [Ul2(MeCN)7][Ul6], [Ul4(py)3], and [U(dmf)9]l4.
AB  - Reaction of UCl4 and excess Me3Sil in acetonitrile provides a convenient route to
      [Ul4(MeCN)4] (1), which was isolated in excellent yield and crystallized in
      acetonitrile as the ion pair complex [Ul2(MeCN)7][Ul6] (2). Compound 1 was
      transformed in pyridine (py) and dimethylformamide (dmf) into the Lewis base
      adducts [Ul4(py)3] (3) and [Ul4(dmf)6] (4). Crystals of 3 and [U(dmf)9]l4 (5)
      were obtained by slow diffusion of diethyl ether into pyridine or dmf solutions
      of 1; compound 5 is the first tetracationic {U4+} entity to have been
      crystallographically characterized.

PMID- 15859297
TI  - Synthesis and X-ray crystal structure of a cationic homoleptic (SPS)2Rh(III)
      complex and EPR study of its reduction process.
AB  - Oxidation of the square planar Rh(I) complex [Rh(SPS(Me))(PPh3)] (SPS(Me) = 1
      methyl-1-P-2.6-bis(diphenylphosphinosulfide)-3,5-(bisphenyl)-phosphinine) (1)
      based on mixed SPS-pincer ligand with hexachloroethane yielded the Rh(III)
      dichloride complex [Rh(SPS(Me))(PPh3)Cl2] (2), which was structurally
      characterized. The homoleptic Rh(III) complex [Rh(SPS(Me))2][Cl] (4) was obtained
      via the stoichiometric reaction of SPS(Me) anion (3) with [Rh(tht)3Cl3] (tht =
      tetrahydrothiophene). Complex 4, which was characterized by X-ray diffraction,
      was also studied by cyclic voltammetry. Complex 4 can be reversibly reduced at E
      = -1.16 V (vs SCE) to give the neutral 19-electron Rh(II) complex [Rh(SPS(Me))2]
      (5). Accordingly, complex 5 could be synthesized via chemical reduction of 4 with
      zinc dust. EPR spectra of complex 5 were obtained after electrochemical or
      chemical reduction of 4 in THF or CH2Cl2. Hyperfine interaction with two
      equivalent 31P nuclei was observed in liquid solution, while an additional
      coupling with a spin 1/2 nucleus, probably 103Rh, was detected in frozen
      solution. The 31P couplings are consistent with DFT calculations that predict a
      drastic increase in the axial P-S bond lengths when reducing (SPS(Me))2Rh(III).
      In the reduced complex, the unpaired electron is mainly localized in a rhodium
      d(z2) orbital, consistent with the g-anisotropy measured at 100 K.

PMID- 15859298
TI  - Photodynamic therapy.

PMID- 15859299
TI  - Pain, pain relief and other practical issues in photodynamic therapy.

PMID- 15859300
TI  - Non-surgical treatment of skin cancer.

PMID- 15859301
TI  - Clinical efficacy of methyl aminolaevulinate photodynamic therapy in basal cell
      carcinoma and solar keratosis.

PMID- 15859303
TI  - Practical aspects of methyl aminolaevulinate photodynamic therapy.

PMID- 15859302
TI  - Topical photodynamic therapy for Bowen's disease.

PMID- 15859304
TI  - Methyl aminolaevulinate photodynamic therapy in practice: treatment protocol.

PMID- 15859305
TI  - Methyl aminolaevulinate photodynamic therapy for Bowen's disease: a practical
      option?

PMID- 15859306
TI  - Photodynamic diagnosis of non-melanoma skin cancer.

PMID- 15859307
TI  - Photodynamic therapy of dermatoses other than non-melanoma skin cancer.

PMID- 15859308
TI  - The HPV test in cervical screening: a brave new world?

PMID- 15859309
TI  - Clinical relevance of human papillomavirus testing in cytopathology.
AB  - Cancer of the uterine cervix is the second most common cancer in women worldwide.
      Currently, cervical screening is based on cytology alone. Because infection with
      high-risk human papillomavirus types (hrHPVs) is a necessary cause of cervical
      cancer, it has been postulated that screening might become more efficient when it
      is based on combined cytology and hrHPV testing. In this review we will discuss
      the advantages of added HPV tests in cervical cancer screening, as a quality
      control for false-negative smears, in triage of women with equivocal smears, in
      follow-up of women treated for CIN3 or cervical cancer and for the detection of
      cervical adenocarcinoma.

PMID- 15859310
TI  - Can we detect cervical human papillomavirus (HPV) infection by cytomorphology
      alone? Diagnostic value of non-classic cytological signs of HPV effect in
      minimally abnormal Pap tests.
AB  - OBJECTIVE: Our aim was to assess the validity of non-classical cytological signs
      in minimally abnormal cervical smears for the prediction of HPV infection.
      METHODS: 164 ThinPrep monolayers were re-screened for mild nuclear changes,
      disorders of keratinisation, abortive koilocytes and 'measles cells', as well as
      degenerative changes. HPV DNA was detected by GP5+/6+ and MY09/MY11 consensus
      primer PCR assays. RESULTS: Seventy six of 164 cases (46.3%) had HPV positivity
      by PCR. All cytomorphological features studied were significantly associated with
      the presence of HPV. Mild nuclear changes had 100% sensitivity and 100% negative
      predictive value for HPV infection. CONCLUSIONS: Our results indicate that non
      classic cytomorphological signs can improve the sensitivity of cytology for
      detecting HPV. Minimally abnormal Pap smears lacking mild nuclear changes (16%)
      in the present study--do not require further molecular HPV testing.

PMID- 15859311
TI  - HPV triage of women with atypical squamous cells of undetermined significance: a
      3-year experience in an Italian organized programme.
AB  - OBJECTIVE: The purpose of our study was to determine if Hybrid Capture II assay
      (HCII) on Liquid Based Cytology (LCB) improves the accuracy (higher sensitivity,
      similar specificity) than the repeat conventional Pap smear in smears with
      Atypical Squamous Cell (ASC) of Undetermined Significance diagnosis. METHODS: HPV
      testing was used to manage women, especially the older ones, with cervical
      abnormalities detected through our triennial organized screening in order to
      avoid unnecessary colposcopy and excessive follow-up if the woman is HPV
      negative. The HPV DNA Triage was offered without any charge to 909 women with
      ASC. The Bethesda System was used for the classification of these equivocal
      cytological findings and more precisely the 1991 version (ASCUS) until the summer
      2001 (315 cases) and the new one 2001 classification (ASC-US and ASC-H) after
      this date (594 cases). The presence or absence of a cervical intraepithelial
      neoplasia of grade I or worse [CIN1+], and of grade II or worse [CIN2+], was
      confirmed by biopsy. RESULTS: The HPV DNA Triage showed a good accuracy
      (specificity over 94%, sensitivity of 37% and PPV for CIN2+ lesions around 30%).
      The higher values of ASC-H lesions (.462) for the sensitivity for CIN 2+ probably
      signify that this lesion is already a SIL. CONCLUSIONS: Our data were comparable
      with those recently published on the meta-analysis by Arbyn et al., confirming
      the promising approach of our guidelines for the treatment of these patients even
      in terms of Health Technology Assessment (HTA).

PMID- 15859312
TI  - Searching for RET/PTC rearrangements and BRAF V599E mutation in thyroid aspirates
      might contribute to establish a preoperative diagnosis of papillary thyroid
      carcinoma.
AB  - OBJECTIVE: Searching for multiple molecular markers in thyroid aspirates appears
      to be a promising approach for establishing a preoperative diagnosis of papillary
      thyroid carcinoma (PTC). METHODS: Based on this hypothesis, a total of 63 samples
      from 55 patients, were collected at random. RNA was extracted from the residue
      cells inside the needle used for fine needle aspiration cytology (FNAC) and
      thereafter molecular analysis was carried out both for RETrearrangements (type 1,
      2, 3) and BRAF codon 599 mutation molecule. Results were compared with the
      cytological and histopathological diagnoses in 24 patients submitted to surgery.
      RESULTS: 58% PTCs presented a genetic alteration either RET/PTC rearrangement,
      BRAF V599E mutation or both: three cases of PTCs (25%) presented a RET/PTC
      rearrangement; three cases of PTCs (25%) presented a BRAF V599E mutation and in
      one case (8%) both alterations were identified. CONCLUSIONS: The present results
      suggest that searching for multiple molecular markers in thyroid aspirates may
      enhance the accuracy of FNAC and refine preoperative diagnosis of PTC.

PMID- 15859313
TI  - The role of liquid-based cytology associated with curettage in the investigation
      of endometrial lesions from postmenopausal women.
AB  - OBJECTIVE: This study investigates the role of liquid-based cytology with
      ThinPrep technique, in the detection of endometrial lesions, using direct
      endometrial sampling from postmenopausal women with the Endogyn endometrial
      device. METHODS: It was performed on 491 postmenopausal women referred to our
      clinic for abnormal bleeding or other symptoms and/or a thickness of endometrium
      >5 mm on ultrasound. Endometrial sampling, dilatation and curettage (D&C) and
      hysterectomy were performed on all patients. For the diagnosis, the WHO
      classification scheme was used. RESULTS: According to our findings a sensitivity
      of 98.08%, specificity of 100%, positive predictive value of 100%, negative
      predictive value of 100% and overall accuracy of 98.98% were observed in both
      endometrial sampling and in D&C. CONCLUSIONS: Endometrial sampling is
      complementary to D&C for the diagnosis of endometrial lesions and it is necessary
      for it to be performed before D&C and/or hysterectomy.

PMID- 15859314
TI  - Abnormal glandular cells in cervical smear.

PMID- 15859315
TI  - Cytomorphological features of metastatic mammary lobular carcinoma in
      cervicovaginal smears: report of a case and review of literature.

PMID- 15859316
TI  - Idiopathic retroperitoneal fibrosis--a potential pitfall for fine needle
      aspiration cytology.

PMID- 15859317
TI  - ABMSPs in cervical cytology.

PMID- 15859318
TI  - Diagnostic value and cost-effectiveness of bronchial brushings in the diagnosis
      of bronchial malignancy.

PMID- 15859319
TI  - Dual cervical parasitosis in a psychiatric patient.

PMID- 15859320
TI  - [Metabonomics and its applications].
AB  - The concept, characteristics and history of metabonomics are introduced. The
      techniques used in data acquisition and data analysis in metabonomics including
      their advantages and disadvantages are summarized. In data acquisition platform,
      NMR, GC/MS, LC/MS (/MS) are the prevalent techniques although at present, none of
      them is a perfect technique that could meet with the requirement of the
      metabonomics for measuring all metabolites. While in data analysis, the PCA, PLS
      and ANN are the major techniques. The researchers could select them according to
      the research destination. Recent advances and applications of metabonomics in
      disease diagnosis, drug toxicity evaluation, plant metabolomics and microbial
      metabolomics are reviewed. In addition, by giving the situation on the
      establishment of the related corporations, the conferences about metabonomics and
      proclamation of NIH roadmap the current boom of the metabonomics is reflected. It
      can be expected that with the development of the function genomics, metabonomics
      will play a major role in the discovery of the phynotype of the genome and
      searching for the disease diagnostic biomarkers, and it will also bring much
      benefit to the drug discovery, clinical diagnosis and nutrition science.

PMID- 15859321
TI  - [Recent advances in structures and relative enzyme properties of xylanase].
AB  - Xylanase can hydrolyze xylans into xylooligosaccharides and D-xylose, and has
      great prospect for applications in feed industry, paper and pulp industry, food
      industry and environment science. The study of xylanase had been started in
      1960's. With the development and application of the new technologies, such as
      molecular biology, structural biology and protein engineering, many progresses
      have been made in the research of structures and functions of xylanase. This
      paper reviews the research progress and trend in the structure correlating with
      the important properties of xylanase. Analyses of three-dimensional structures
      and properties of mutants have revealed that glutamine and aspartic acid residues
      are involved in the catalytic mechanism. The thermostability of xylanase
      correlated with many factors, such as disulfide bridges, salt bridges, aromatic
      interactions, cotent of arginine and proline, and some multidomain xylanase have
      thermostability domains in N or C terminal. But no single mechanism is
      responsible for the remarkable stability of xylanase. The isoelectic points and
      reaction pH of xylanase are influenced by hydrophobicity and content of electric
      charges. Many researches had demonstrated that aromatic amino acid, histidine,
      and tryptophan play an important role in improving enzyme-substrate affinity. The
      researches of structures and functions of xylanase are of great significance in
      understanding the catalytic mechanism and directing the improvement of xylanase
      properties to meet the application requirement.

PMID- 15859322
TI  - [NF-kappaB tumorigenesis and drug developement].
AB  - NF-kappaB, a collective name of dimeric transcription factors, is composed of
      members of the Rel family proteins that recognize and bind a specific DNA
      sequence. It is normally sequestered in the cytoplasm of non-stimulated cells by
      associating with a family of inhibitor proteins called IkappaBs. Exposure of
      cells to a variety of extra-and intra-cellular stimuli leads to the rapid
      proteolytic degradation of IkappaBs, which frees NF-kappaBs allowing them to
      translocate to the nucleus where it regulates gene transcription. NF-kappaB is
      involved in a lot of physiological processes such as immunity, inflammation, cell
      proliferation, apoptosis and even tumorigenesis by regulating the transcription
      of a larger number of genes. This review introduces the various mechanisms of NF
      kappaB activation including a recently reported alternative activation pathway
      mediated by lymphotoxin alpha/beta, B cell activating factor and CD40 ligand. The
      signal transduction pathway leading to NF-kappaB activation via IKK in response
      to proinflammatory factors like TNF-alpha and IL-1 is addressed in more detail
      concerning the regulation of IKK activity, mechanism of IkappaB degradation and
      regulation of transactivation activity of NF-kappaB on different levels.
      Considering the important role of NF-kappaB in cell proliferation and regulation
      of various genes participating in apoptosis, the involvement of NF-kappaB in
      tumorigenesis and drug screening is also discussed.

PMID- 15859323
TI  - Specific identification of (R)-3-hydroxyacyl-ACP: CoA transacylase gene from
      Pseudomonas and Burkholderia strains by polymerase chain reaction.
AB  - Polyhydroxyalkanoates (PHA) were biodegradable thermoplastics. Due to their broad
      applications, direct biosynthesis of PHA from inexpensive substrates, such as
      carbohydrates, is actively pursued. It has been recently revealed that (R)-3
      hydroxyacyl-ACP: CoA transacylase (PhaG) played an important role in this
      pathway. In this study, a polymerase chain reaction (PCR) protocol was developed
      for the rapid and specific identification of phaG gene from various bacteria.
      Using the PCR strategy, the complete open reading frames of two phaG genes from
      Pseudomonas stutzeri 1317 and Pseudomonas nitroreducens 0802 were cloned from the
      genomic DNA and functionally expressed in Pseudomonas putida PHAGN-21.
      Furthermore, this strategy was successful applied in non-Pseudomonas strains,
      such as Burkholderia. These results suggest that PhaG-mediated pathway of medium
      chain-length polyhydroxyalkanoates was widespread among bacteria.

PMID- 15859324
TI  - [Cloning of mMR-1 gene and expression in Pichia pastoris systems].
AB  - hMR-1 (Homo Myofibrillogenesis Regulator 1, AF417001) is a novel homo gene, which
      was firstly cloned in our laboratory. The former studies revealed that hMR-1 is a
      transmembrane protein which shows protein interaction with sarcomeric proteins
      like myomesin I, myosin regulatory light chain, alpha-enolase and some cell
      regulator proteins such as eukaryotic translation initiation factor3 subunit 5
      (eIF3S5) and etc. In this work, we focused on cloning the homologous gene of hMR
      1 from mouse C57BL/6J and exploring its expression using Pichia pastoris yeast
      system. Two pairs of primers were synthesized according to the hMR-1 gene
      homologous sequence on mouse genome chromosome 1. The mouse MR-1 gene (mMR-1) was
      cloned by PCR following the first round RT-PCR from mouse C57BL/6J spleen total
      RNA. Sequence analysis verified that mMR-1 gene and amino acids sequence showed
      90.4% and 90.1% identity with hMR-1, respectively. The prediction of hydrophobic
      transmembrane structure of mMR-1 suggested it is also a transmembrane protein.
      The mMR-1 Pichia pastoris expression vector pPIC9-mMR-1 was constructed by fusion
      of the flanking mMR-1 ORF in the pPIC9 plasmid. After linearization of pPIC9-mMR
      1 with Sal I, the 8.5kb DNA fragment was transformed into Pichia pastoris GS115
      strain by electroporation. GS115/Mut+ pPIC9-mMR-1 transformants were selected on
      minimal methanol medium. Integration of mMR-1 gene into the yeast genome in the
      recombinants was verified by PCR from the transformants total DNA. The mMR-1
      protein was expressed by induction under the concentration of 0.5 % methanol. The
      specific induced protein of 25 kD molecular mass in SDS-PAGE was confirmed to be
      the mMR-1 protein by Western blot rsing hMR-1 polyclonal antibody. The expression
      level of this recombinant mMR-1 protein was about 50 mg/L. The successful
      expression of mMR-1 in the Pichia pastoris GS115 will facilitate the further
      functional analysis of the novel gene MR-1 in animal model.

PMID- 15859325
TI  - [Screening of TACE peptide inhibitors from a phage display random 15-peptide
      library by recombinant TACE ecotodomain].
AB  - Tumour necrosis factor-alpha converting enzyme (TACE) is the major protease
      responsible for processing proTNF from membrane-anchored precursor into secreted
      TNF-alpha. It was validated that TACE is involved in many diseases such as
      arthritis, multiple sclerosis and Alzheimers, therefore it represents a novel and
      significant target for therapeutic intervention in a variety of inflammatory and
      neuroimmunological diseases. To obtain the recombinant TACE ectodomain and use it
      as a selective molecule for the screening of TACE peptide inhibitors, the cDNA
      coded for catalytic domain (T800) and full-length ectodomain (T1300) of TACE were
      amplified by RT-PCR, the expression plasmid was constructed by inserting
      T800/T1300 into plasmid pET-28a/pET-28c and transformed into E. coli BL21 (DE3).
      SDS-PAGE and Western blotting analysis revealed that T800/T1300 was highly
      expressed in the form of inclusion body being induced by IPTG. After Ni2+ -NTA
      resin affinity chromatography, the purity of the recombinant T800/T1300 protein
      was more than 90%. T800 and T1300 protein were used in the screening of TACE
      binding peptides from the phage display random 15-peptide library. After four
      rounds of biopanning, the positive phage clones were analyzed by ELISA,
      competitive inhibition assay and DNA sequencing. A common amino acid sequence
      TRWLVYFSRPYLVAT was found and synthesized. The synthetic peptide was shown to
      bind to TACE and inhibit the TNF-alpha release from LPS-stimulated human
      peripheral blood mononuclear cells (PBMC) up to 60.3%. FACS analysis revealed
      that the peptide mediated the accumulation of TNF-alpha on LPS-stimulated PBMC
      surface. These results demonstrate that the TACE-binding peptide is an effective
      antagonist of TACE and the deduced motif might be applied to molecular design of
      anti-inflammation drugs.

PMID- 15859326
TI  - [Transfection and expression of hRI gene on human umbilical blood stem cells and
      gene therapy for mouse melanoma].
AB  - In order to explore the transfection and expression of hRI gene on human
      umbilical blood stem cells, and observe it's effect on the tumor growth. After
      enriching human umbilical cord blood CD34+ cells with a high-gradient magnetic
      cell sorting system (MACS), transfected them with supernatant of retrovirus
      containing human Ribonuclease inhibitor (hRI) cDNA. Hematopoietic progenitor
      clonogenic assay and PCR were used to evaluate transfection efficiency, and
      Western-blot and immune fluorescence were used to evaluate the expression
      quantity of hRI gene after transfection. Observe the effect of RI on the growth
      of melonoma in B16C57BL mice. The results showed that human umbilical blood CD34+
      cells were highly purified by MACS, which made the purity of human umbilical
      blood CD34+ cells average 96.15%. hRI can be transfected on umbilical blood CD34+
      cells, and the transfection efficiency was 35%. The positive expression of hRI
      gene on transfected CD34+ cells is identified by Western-blot and immune
      fluorescence assay. Mice injected with transfected CD34+ cells show a significant
      restraint of the tumor growth, a lower efficiency of tumor formation, a lower
      weight of the tumor and a longer incubation period of tumor formation with
      respect to the control groups. The results demonstrated the capacity of RI to
      inhibited the tumor growth by blocking the vasculature in tumor.

PMID- 15859327
TI  - [Development of a fusion toxin IL15M-PEdelta293 based on a receptor-specific IL
      15 antagonist].
AB  - IL-15 and IL-15 receptors (IL-15R) play a crucial role in the pathogenesis of
      adult T-cell leukemia (ATL), multiple myeloma and inflammatory autoimmune
      diseases. To develop a novel therapeutic agent capable of eliminating IL-15R-over
      expressing abnormal cells, the gene coding for human IL-15 antagonist (IL-15M)
      was fused with a DNA fragment coding for the mutated form of Pseudomonas
      exotoxin, PEdelta293. The resulting gene fusion was cloned into pET16b under the
      control of T7 promoter, giving rise to the expression plasmid pET-IL15M
      PEdelta293. Using Ni2+ -NTA affinity chromatography, IL15M-PEdelta293 was
      purified from E. coli BL21 (DE3) pLysS transformed with pET-IL15M-PEdelta293. The
      fusion toxin showed cytotoxicity to IL-15R-bearing myelogenous leukemia cell line
      K562 and K562-derived multidrug resistant cell line K562/AO2. However, IL-15R
      negative cell line Jurkat was insensitive to IL15M-PEdelta293. In addition, the
      toxic effect of IL15M-PEdelta293 on K562 was completely blocked by excessive
      amount of recombinant human IL-15. These results demonstrated that the selective
      cytotoxicity of IL15M-PEdelta293 correlated with the appropriate IL-15R
      expression on target cells. The present data suggest that the chimeric toxin
      constructed in this report may have therapeutic potential in the treatment of
      diseases associated with abnormal expression of IL-15/IL-15R, even in the
      treatment of chemotherapy refractory tumors.

PMID- 15859328
TI  - [Characterization of murine leukemia virus recombinants that express H5N1 subtype
      avian influenza virus hemagglutinin glycoproteins].
AB  - One highly pathogenic strain of avian influenza virus (AIV) was isolated from
      goose in China recently, designated as F-3. In order to study the viral entry
      mechanisms, the hemagglutinin (HA) gene of H5N1 subtype AIV isolate was amplified
      by RT-PCR, and then cloned into pGEM-T vector and sequenced. The sequencing
      result has logging in GenBank, the accession number was AY639405. The HA gene of
      F-3 had a complete open reading frame (ORE) and composed of 1707 nucleotides,
      coding for 568 amino acids. The deduced amino acid sequence at the cleavage site
      of the HA protein was RKKR GLF, matched to the characteristic of virulent avian
      influenza strain. The HA gene were subcloned into pcDNA3, so the plasmid pcDNA-HA
      can express the HA glycoprotein. Co-transfected pcDNA-HA, pHIT60 (include Murine
      Leukemia Virus structural genes, namely gag and pol) and pHIT111 (retroviral
      vector genome,containing LacZ as a reporter) into 293T cells. The retroviral
      supernatant were harvested 48 hours post-transfection, filtered through 0.45
      micromol/L filter. The supernatant were used to analysis the characteristic of
      the pseudotyping virions by Western blotting and infection test. Western blotting
      revealed the HA glycoproteins can be expressed on the virions, indicated the
      glycoproteins were incorporated onto the retroviral virions. Infection test were
      performed on 293T, NIH3T3 and COS-7, all the three kinds of cells infected were
      lacZ positive, indicating viral entry, and revealed the pseudotype virions of
      MuLV-HA were infectious. So the pseudotype system of MuLV particles with AIV
      Hemagglutinin proteins were setted up and it can be used to study the entry of
      avian influenza virus isolated from goose in China.

PMID- 15859329
TI  - [Hydrophobicity of reactive site loop of SCCA1 affects its binding to HBV].
AB  - Squamous cell carcinoma antigen 1 (SCCA1), a member of the ovalbumin family of
      serine protease inhibitors, includes several variants. It was reported that
      expression of two SCCA1 (BP and AJ515706) in cells results in increased binding
      of HBV to these cells by the interaction of the expressed BP and AJ515706 with
      HBV pre-S1 domain. In this study, a SCCA1 (A1) was isolated from HepG2, but it
      appears to lack this ability. A possible role of two mutants, A1-BP and BP-A1,
      constructed by interchanging the carboxyl terminal of A1 and BP, was
      investigated. Cells expressing A1-BP rather than BP-A1 showed an increased virus
      binding capacity. Comparison of A1 sequence with the sequence of BP indicated the
      presence of only three amino acid changes in the carboxyl terminal, two of them
      in the reactive site loop (RSL) of SCCA1. Primary structure analysis revealed
      that the hydrophobicity of BP and AJ515706 in this domain is higher than that of
      A1. Changing the aa349 of A1 from low hydrophobic glutamic acid to high
      hydrophobic valine enhanced HBV binding. In contrast, changing the aa349 of BP
      from valine to glutamic acid reduced HBV binding. Our finding suggests that the
      hydrophobicity of RSL of SCCA1 may play an important role in HBV binding to
      cells.

PMID- 15859330
TI  - [Establishment of embryogenic cell suspension culture and plant regeneration of
      edible banana Musa acuminata cv. Mas (AA)].
AB  - Conventional breeding for dual resistance of disease and pest of Musa cultivars
      remains a difficult endeavor, as the plant is polyploidic and high in sterility.
      Biotechnological techniques, eg., genetic engineering, in vitro mutation
      breeding, or protoplast fusion, may overcome the difficulties and improve the
      germplasm. Establishment of a stable embryogenic cell suspension (ECS) is a
      prerequisite for any of the biotechnological breeding methods. In this study an
      embryogenic cell suspension was established from immature male flower of Musa
      acuminata cv. Mas (AA), a popular commercial variety of banana in the South-East
      Asian region. After culture for 5-6 months on callus induction media, which
      consisted of MS salts, different concentrations of 2,4-dichlorophenoxyacetic acid
      (2,4-D), 4.1 micromol/L biotin, 5.7 micromol/L indoleacetic acid (IAA), 5.4
      micromol/L naphthaleneacetic acid (NAA), other vitamins, 87 mmol/L sucrose, and
      solidified with 7 g/L agarose, meristematic globules and yellow, friable
      embryogenic cultures were induced from the explants of 1-15th row young floral
      hands of immature male flowers. Of the four treatments of 2,4-D, 9 micromol/L was
      the most effective on the callus induction, it transformed 40.96% and 7.45% of
      the cultivated male floral hands into callus and embryogenic callus respectively.
      The explants to produce highest frequency of the embryogenic calli were floral
      hands of 6 to 12th rows, which generated 5.79% of the embryogenic calli.
      Suspension cultures were initiated from these embryogenic calli in liquid medium
      supplemented with 4.5 micromol/L 2, 4-D. After sieving selection of the cultures
      using a stainless steel metallic strainer with pore sizes of 154 microm at 15 day
      intervals for 3 months, homogeneous and yellow embryogenic cell suspensions,
      composed of single cells and small cell aggregates, were established. Based upon
      the growth quantity and growth rate of ECS, it was determined that the
      appropriate inoculum was 2.0 mL PCV ECS/30 mL medium in 100 mL flask, and the
      appropriate subculture cycle was 15 days. Planting of 6 months old ECS on semi
      solid medium of somatic embryo induction and development (MSD) resulted in
      approximately 280 x 10(3) somatic embryos/mL PCV ECS. MSD contained SH
      macronutrients, micro-nutrients, Fe-EDTA and MS vitamins supplemented with 4.5
      micromol/L biotin, 680 micromol/L glutamine, 2 mmol/L proline, 100 mg/L malt
      extract, 1.1 micromol/L NAA, 0.2 micromol/L zeatin, 0.5 micromol/L kinetin, 0.7
      micromol/L N6-(2-isopentenyl) adenine, 29 mmol/L lactose, 130 mmol/L sucrose and
      solidified with 2g/L gelrite. After 3 months of maturity on MSD, 17.28% of the
      somatic embryos were germinated on germination media (MG), consisted of MS salt,
      Morel and Wetmore vitamins, 0.2 micromol/L 6-BA, 1.1 micromol/L IAA, 87
      micromol/L sucrose and solidified with 2 g/L gelrite; and 14.16% of the somatic
      embryos could develop into normal plantlets on rooting media contained the same
      composition as that of MG but without auxin and cytokinin.

PMID- 15859331
TI  - [Enhancement of hypericin production and cell growth of Hypericum perforatum L.
      suspension cultures by nitric oxide].
AB  - Nitric oxide has emerged as a key signaling molecule in plants recently. The role
      of nitric oxide in elicitor-induced defense responses of plants has been
      extensively investigated. In this work, sodium nitroprusside was utilized as the
      donor of nitric oxide to investigate the effects of exogenous nitric oxide on
      hypericin production and cell growth of suspension cell cultures of Hypericum
      perforatum L.. Compared with the untreated Hypericum perforatum L. suspension
      cells, external application of 0.5 and 15.0 mmol/L sodium nitroprusside induced
      1.4 and 0.5-fold dry cell weight, and 0.9 and 2.1-fold hypericin content
      respectively. The results showed that low concentration of sodium nitroprusside
      promoted the growth of Hypericum perforatum L. suspension cells, while high
      concentration of sodium nitroprusside enhanced hypericin biosynthesis in
      Hypericum perforatum L. suspension cells. The maximum hypericin production was
      achieved by adding 0.5 mmol/L and 15.0 mmol/L sodium nitroprusside to the culture
      at day 0 and day 14 respectively, increasing the total hypericin yield by nearly
      3.2-fold. The effects of sodium nitroprusside on hypericin content and growth of
      Hypericum perforatum L. suspension cells were abolished by nitric oxide specific
      scavenger 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, which
      indicated that the effects of the application of sodium nitroprusside were caused
      by nitric oxide released from sodium nitroprusside rather than sodium
      nitroprusside itself. The results also showed that 15.0 mmol/L sodium
      nitroprusside stimulated the activities of phenylalanine ammonia-lyase (PAL), one
      of the key enzymes of phenylpropanoid pathway, in suspension cells of Hypericum
      perforatum L., which suggested that the synthetic pathway of hypericin might be
      activated by NO through triggering the defense responses of Hypericum perforatum
      L. suspension cells.

PMID- 15859332
TI  - Purification and characterization of a monofunctional catalase from an
      alkaliphilic Bacillus sp. F26.
AB  - An alkaline catalase has been purified and characterized from a slightly
      halophilic and alkaliphilic bacterium Bacillus sp. F26. The purification was
      performed with a four step procedure consisting of ammonium sulfate
      precipitation, ion exchange, gel filtration and hydrophobic interaction
      chromatography, and finally achieved a 58.5-fold-purifying over the crude
      extract. The purified catalase was composed of two identical subunits with a
      native molecular mass of 140 kD. The native enzyme showed the typical Soret band
      appearing at 408 nm. The pyridine hemochrome spectrum indicated the presence of
      protoheme IX as the prosthetic group. The apparent Km value for enzyme activity
      on H2O2 was calculated to be 32.5 mmol/L. The activity of this catalase was not
      reduced by dithionite but was strongly inhibited by cyanide, azide, and 3-amino
      1,2,4-triazole (the specific inhibitor of monofunctional catalase). No peroxidase
      activity of this enzyme was detected when using o-dianisidine, diaminobenzidine
      (DAB) and p-phenylenediamine as electron donor. Moreover, the N-terminal sequence
      of this catalase exhibited substantial similarity to the monofunctional catalase
      subgroup rather than catalase-peroxidase or Mn-catalase one. Therefore, we
      characterize the purified catalase as a monofunctional catalase. Besides, this
      monofunctional catalase was thermosensitive and its activity exhibited pH
      independent over pH 5-9 but showed a sharp maximum at pH 11. An activity half
      life of approximately 49 h was measured when the enzyme was incubated at 20
      degrees C and pH 11. To our knowledge, pH 11 is the most alkaline condition for
      optimum catalysis and enzyme stability among the catalases reported up to now.
      Furthermore, this monofunctional catalase also showed excellent halo-alkali
      stability with a half-life of approximately 90 h at 0.5 mol/L NaCl and pH 10.5.
      On the other hand, so far as we know, the characterized catalase is the first
      dimeric monofunctional catalase from alkaliphiles and is also the first
      monofunctional catalase derived from a natural soda lake, which could partially
      reflect the oxidative stress response in the corresponding environment.

PMID- 15859333
TI  - [Expression of acidophilic alpha-amylase from Alicyclobacillus acidocaldarius].
AB  - The alpha-amylase (EC 3.2.1.1) from the Gram-positive Alicyclobacillus
      acidocaldarius was one kind of thermoacidophilic enzyme, with optimal temperature
      and pH of 75 degrees C and 3, respectively. The nucleotide sequence of the gene
      amy was cloned by PCR. The gene amy was 3901bp long, comprising one open reading
      frame encoding a polypeptide of 1301 amino acids. The calculated molecular weight
      of the alpha-amylase AMY was about 140kD. The gene amy was expressed in E. coli
      BL21 (DE3) and Pichia pastoris respectively, and both of the cloned proteins had
      bioactivity. The activity of amylase expressed in P. pastoris was further
      testified by amylase activity staining. The alpha-amylase expressed in P.
      pastoris had been purified and characterized. The apparent molecular weight of
      that was about 160kD according to SDS-PAGE. The optimum of pH for the enzyme was
      pH 3.2 as the native enzyme was; but the optimum of temperature was 65 degrees C
      and a little lower than that of the native enzyme. Above 50% of relative activity
      remained after incubation for 30 minutes in 70 degrees C. So the enzyme expressed
      by P. pastoris was also thermoacidophilic. Moreover some sequence was cloned by
      PCR, which ranged from + 1174 bp to + 3288 bp in the gene amy, encoding 705 amino
      acids with the calculated molecular weight of 79kD. The truncated gene amy' was
      expressed in E. coli BL21 (DE3) induced by 1 mmol/L IPTG, and the expressed
      enzyme also retained alpha-amylase activity.

PMID- 15859334
TI  - [The structure-function relationship of thermostable beta-glycosidase from the
      thermophilic eubacterium Thermus nonproteolyticus HG102].
AB  - Beta-glycosidase (Tngly) from the thermophilic eubacterium Thermus
      nonproteolyticus HG102, which is a thermostable monomeric protein and adopts the
      (beta/alpha)8 barrel fold, is an excellent model system to be investigated for
      the thermostable mechanism, activity and substrate specificity. Here, based on
      the analysis of structural basis for thermostability of Tngly (Wang et al, 2003)
      and comparison of other proteins structure of homofamily, Glu164 and Glu338 may
      act as proton donor and nucleophile in the hydrolysis reaction respectively;
      proline located at N1 of alpha-helix and arginine which can form ion link may
      contribute to the thermostability. We aim to further identify the critical sites
      and the amino acid residue(s) responsible for the activity, the thermal stability
      and the substrate specificity. Mutations had been constructed by site-directed
      mutagenesis. They are Glu164Gln, Glu338Ala, Pro316Gly, Arg325Leu, Pro344Phe,
      Pro356Ala and Pro316Gly/Pro356Ala. All mutant proteins were purified to SDS-PAGE
      purity. Changes in the conformations were examined by means of CD. The Glu338Ala
      mutant showed no detectable hydrolysis activity, but can synthesize
      oligosaccharides, as expected for the residue acting as the nucleophile of the
      reaction. The Glu164 acts as the general acid/base catalyst in the hydrolysis
      reaction. Changes in stabilities of mutants compared with wild-type were
      determined by means of heat inactivity experiment. These results indicate that
      the amino acid residue of proline that is located at N1 positions of alpha-helix,
      and Arg325 that form salt bridge between alpha-helices 5 and alpha-helices 6, are
      the critical sites to protein thermostabilization.

PMID- 15859335
TI  - [Solid-phase synthesis and biological characterization of S12A-HNTX-IV and R29A
      HNTX-IV: two mutants of hainantoxin-IV].
AB  - Hainantoxin-IV (HNTX-IV) purified from the venom of the spider Selenocosmia
      hainana is a potent antagonist that acts on tetrodotoxin-sensitive (TrX-S) sodium
      channels. It is a 35-residue polypeptide and includes three disulfide bridges. In
      order to investigate the structure-function relationship of HNTX-IV, two mutants
      (S12A-HNTX-IV and R29A-HNTX-IV) of HNTX-TV in which Ser12 and Arg29 were replaced
      by Ala respectively, were synthesized by solid-phase Fmoc chemistry, followed by
      oxidative refolding of purified peptides under the optimal conditions. The
      synthetic mutants were analyzed by MALDI-TOF mass spectrometry, nuclear magnetic
      resonance spectroscopy (NMR) and electrophysiological experiments for molecular
      weight, conformation and physiological activity, respectively. The results show
      that the mutants and native HNTX-IV (nHNTX-IV) have almost identical three
      dimensional structures. The bioactivity level of S12A-HNTX-IV is also about the
      same as that of nHNTX-IV, suggesting that Ser12 does not play any important role
      for the bioactivity of this toxin. The bioactivity of R29A-HNTX-IV is reduced by
      at last 155 times, indicating that Arg29 is a key residue relative to the
      bioactivity of HNTX-IV. It is presumed that the decrease in activity of R29A-HNTX
      IV is due to the changes of the property in the binding site rather than the
      change in the basic conformation of the molecule.

PMID- 15859337
TI  - [Neural network detection of abnormalities in fed-batch fermentation].
AB  - During fermentation, it is often difficult to detect the abnormalities, for
      example, caused by contamination on-line. Instead, the faults were detected
      usually by off-line laboratory analysis or other ways, which in most cases, is
      too late to remedy the situation. In this paper, a simple three-layers BP network
      was used for the early prediction of the amount of product, based on the
      difference in prediction errors between normal and abnormal charges and other
      accessorial information, such as profit function and pH value. In addition, three
      indications characteristic to abnormal charge are incorporated in practical
      operation. The prediction for Cephalosporin C Fed-batch Fermentation in a Chinese
      pharmaceutical factory was studied in details as an example and the result shows
      the abnormal charge can be discovered early successfully using the method.

PMID- 15859336
TI  - [Construction and characterization of TetR and GFP fusion protein].
AB  - Tetracycline repressor gene (tetR) from E. coli transposon Tn10 was fused in
      frame with green fluorescent protein gene (gfp) from jellyfish Aequorea Victoria
      on an E. coli expression vector and the fusion protein (TR::GFP) was purified.
      The binding of TR::GFP with tetracycline (tc) was demonstrated by nitrocellulose
      filter binding assay. TR::GFP also maintained the fluorescence property of GFP.
      Most significantly, fluorescence emission intensity of TR::GFP increased by 2
      fold in the presence of tc, from 1.132 to 2.214, while those of GFP and TetR
      showed little change under similar conditions. The results indicated TR::GFP
      possesses characteristics of a tetracycline biosensor.

PMID- 15859338
TI  - [The effect of fermentation conditions on glycosylation of recombinant human
      interferon omega in yeast Pichia pastoris].
AB  - To investigate the influence of the fermentation conditions on glycosylation of
      heterologous recombinant protein in yeast Pichia pastoris, the glycosylation of
      recombinant human interferon omega (rhIFNomega) under various fermentation
      conditions, e. g., cell density, initial pH, methanol concentration, duration of
      the induction, and medium volume were studied. The glycosylation of rhIFNomega in
      the continuous fermentation process under various pH values and in batch
      fermentation were also investigated. In 250 mL flask, the optimal cell density,
      initial pH, medium volume, methanol concentration and frequency of methanol
      induction were 250 g/L (WCW), pH6.0, less than 30 mL, 15 g/L and 3 (in every 24
      h), respectively. In the continuous process, the glycosylation of rhIFNomega
      could be effectively improved by maintaining the pH value at 7.0-7.5. In the
      batch fermentation process, the expression level of glycosylated and non
      glycosylated rhIFNomega were the same, but the specified value of
      glycosylation/non-glycosylation was significantly lower than that in the flask
      culture. The reason of this phenomenon will be further studied. This research lay
      the foundation for the scale-up of production and the enhancement of rhIFNomega
      glycosylation in Pichia pastoris.

PMID- 15859339
TI  - [Continuous ethanol fermentation using self-flocculating yeast strain and
      bioreactor system composed of multi-stage tanks in series].
AB  - A continuous ethanol fermentation system composed of four-stage tank fermentors
      in series and with a total working volume of 4000 mL was established. The first
      fermentor was designated as the seed fermentor and the others for ethanol
      fermentation. A self-flocculating yeast strain developed by protoplast fusion of
      Saccharomyces cerevisiae and Schizosaccharomyces pombe was applied. Two-stage
      corn powder enzymatic hydrolyzate containing reducing sugar 100 g/L, together
      with 2.0 g/L (NH4)2HPO4 and KH2PO4, was used as yeast seed culture medium and fed
      into the seed fermentor at the dilution rate of 0.017h (-1). Meanwhile, the
      hydrolyzate containing reducing sugar 220 g/L, added with 1.5 g/L (NH4)2HPO4 and
      2.5 g/L KH2PO4, was used as ethanol fermentation substrate and fed into the
      second fermentor at the dilution rates of 0.017, 0.025, 0.033, 0.040 and 0.050 h(
      1) (based on the total working volume of the three fermentors), respectively. The
      chemostat states on which all of the monitoring parameters, including residual
      sugar, ethanol and yeast cell biomass concentrations, were maintained relatively
      constant were observed for seed cultivation and ethanol fermentations when the
      fermentation system was operated at the dilution rates of 0.017, 0.025, 0.033 and
      0.050 h(-1). Yeast cells were observed being partly immobilized because
      significant yeast cell biomass concentration differences between the broth out of
      and inside the fermentors were detected. Moreover, the oscillations of residual
      sugar, ethanol and yeast cell biomass concentrations were observed when the
      fermentation system was operated at the dilution rate of 0.040 h(-1). The broth
      containing more than 12% (V/V) ethanol and less than 0.11% (W/V) residual
      reducing sugar and 0.35% (W/V) residual total sugar was produced when the
      dilution rate was controlled at no more than 0.033 h(-1). The ethanol
      productivity was calculated to be 3.32(g x L(-1) x h(-1)) for the dilution rate
      of 0.033 h(-1), which increased nearly 100% compared with that for conventional
      ethanol fermentation technologies using freely suspended yeast cells.

PMID- 15859340
TI  - [Differential effect of temperature on Plt and PCA synthesis in a rsmA
      inactivated mutant strain of Pseudomonas sp. M-18].
AB  - Rsm (repressor of secondary metabolite) A is an mRNA binding protein which
      functions as a global repressor to control multiple genes at the
      posttranscriptional level. Using homologous recombination technique a chromosomal
      rsmA inactivated mutant strain M-18R was constructed in Pseudomonas sp. M-18, a
      strain of plant-growth-promoting rhizobacteria, which could inhibit several
      soilborn phytopathogens by producing secondary metabolites including phenazine-1
      carboxylic acid (PCA) and pyoluteorin (Plt) in one single strain. To further
      study the effect of RsmA on the synthesis of Plt and PCA in the wild type strain
      M-18, the dynamic curves of Plt and PCA produced respectively by M-18 and M-18R
      were measured in KMB medium under different temperature conditions such as 37
      degrees C constant, 28 degrees C constant and nonconstant (37 degrees C 4 hours
      at first and then 28 degrees C constant) cultivation. The synthesis of both Plt
      and PCA were almost inhibited in the cultures under the condition of 37 degrees
      C. At 28 degrees C, however, compared with the wild type strain M-18, the mutant
      strain produced tenfold amount of Plt, while the production of PCA decreased only
      about 50%. When cultivated under the nonconstant condition, the amount of Plt
      produced by M-18R could reach 400 microg/mL while the PCA production was not
      significantly affected, but in the wild type strain M-18, the amount of Plt
      production decreased obviously while the PCA production was not affected in
      comparison with the results at 28 degrees C constant. These results suggest that
      a temperature sensitive factor exists to function as an activator independent of
      RsmA to promote the synthesis of Plt in the rsmA mutant strain M-18R while it may
      bind with RsmA to repress the synthesis of Plt in the wild type strain M-18. But
      this factor did not exert any affect on the synthesis of PCA.

PMID- 15859341
TI  - [Effect of flocculence of a self-flocculating yeast on its tolerance to ethanol
      and the mechanism].
AB  - Investigation was undertaken for the purpose of examining any possible
      correlation between flocculence of a self-flocculating fusant of
      Schizosaccharomyces pombe mutant and Saccharomyces cerevisiae mutant (called
      fusant SPSC for short) and the tolerance of this strain to ethanol. When exposed
      to 18% (V/V) ethanol for 7 h at 30 degrees C, 52%, 37% and 9% of viability levels
      remained for the cells of fusant SPSC and its two parental strains, Sch. pombe
      mutant and S. cerevisiae mutant respectively. Analysis of phospholipid fatty acid
      composition of plasma membrane showed that the content of palmitic acid of each
      flocculating yeast (fusant SPSC or Sch. pombe mutant) was around 2-fold higher
      than that of free S. cerevisiae mutant, with remarkably lower contents of
      palmitoleic and oleic acids than the latter. When 0.1 mol/L sodium citrate was
      initially included in the medium in which cells of each flocculating yeast were
      grown, free cells rather than aggregates were finally obtained. Furthermore, the
      content of palmitic acid in the phospholipid fatty acid composition of the plasma
      membranes of the free cells of each flocculating yeast was found to decrease
      significantly, with a marked increase in the contents of palmitoleic and oleic
      acids. As a result, the characteristics of the phospholipid fatty acid
      composition of the plasma membranes of the free cells of each flocculating yeast
      were similar to those of S. cerevisiae mutant. Meanwhile, the disappearance of
      flocculence of each flocculating yeast caused by the action of sodium citrate
      brought about a steeply decreased tolerance of the free cells to ethanol, thus
      being equivalent to that of S. cerevisiae mutant. These data suggest that the
      stronger ethanol tolerance of each flocculating yeast is related to the higher
      content of palmitic acid in the phospholipid fatty acid composition of the plasma
      membranes. Thus, the enhancement by flocculence on the tolerance of yeast cells
      to ethanol as well as its mechanism are first reported in this work.

PMID- 15859342
TI  - [Purification of ovalbumin from hen egg white by high-speed counter-current
      aqueous two-phase chromatography].
AB  - High-speed counte-recurrent chromatography (HSCCC) is a continuous liquid-liquid
      partition chromatography without solid matrix, which has the significant features
      of high resolution and high recovery. The separation of bio-macromolecule in
      aqueous two-phase systems (ATPs) with HSCCC is still under research, and the
      establishment of high-speed counter-current aqueous two-phase chromatography
      (HSCCC-ATP) relies on the improvement of equipment structure and optimization of
      operation parameters. By using a multi-column high-speed counter-current
      chromatograph, the separation of protein mixture and the purification of
      ovalbumin from hen egg white were studied. The effects of pH and PEG
      concentration on the partition coefficients of proteins were tested in PEG1000
      phosphate ATPs, and distinct differences among partition coefficients of proteins
      were found at pH 9.2 and 15.0% (W/W) PEG concentration in said system. The
      separation of protein mixture, consisting of cytochrome C, lysozyme and myoglobin
      was successfully performed in 15.0% (W/W) PEG1000-17.0% (W/W) potassium phosphate
      ATPs at pH 9.2 with high-speed counter-current chromatograph at rotation speed of
      850r/min and flow rate of 0.8mL/min, using upper phase as stationary phase. pH
      and PEG concentration also had distinct effects on the partition coefficients of
      the major protein components in hen egg white, including ovaltransferrin,
      ovalbumin and lysozyme. The optimal pH value and PEG concentration for the
      purification of ovalbumin by HSCCC-ATP were found to be 9.2 and 16.0% (W/W)
      respectively. Ovalbumin was successfully purified to homogeneity from the hen egg
      white sample in 16.0% (W/W) PEG1000-17.0% (W/W) potassium phosphate ATPs at pH
      9.2 with high-speed counter-current chromatograph at rotation speed of 850r/min
      and flow rate of 1.8mL/min, using upper phase as stationary phase. The
      purification recovery of ovalbumin was around 95%.

PMID- 15859343
TI  - [Expression of capsid gene of Chinese isolate of rabbit hemorrhagic disease virus
      in Pichia pastoris].
AB  - The capsid protein (VP60) gene of RHDV was subcloned into the Pichia expressin
      vector pPICZ B to express the VP60 protein intracellularly. The recombinant
      plasmid was initially transformed into a E. coli strain TOP10 F'. After
      verification of the construct by sequencing, the recombinant plasmid was
      linearized by Sac I in the 5' AOX1 region and then transformed into Pichia
      pastoris strain GS115 using the Pichia EasyComp Kit. After selecting and verifing
      for the insertion of VP60 gene in the genome, two clones of Pichia transformants
      were select for expression test. The recombinant clones were first inoculate with
      BMGY in baffled flask at 28-30 degrees C in a shaking incubator (250-300 r/min)
      until culture reaches an OD600 = 2-6, then resuspend the cell pellet to an OD6oo
      of 1.0 in BMMY medium to induce expression for 5 days by methanol at a
      concentration of 0.5% in a 1 liter baffled flask covered with 2 layers of sterile
      gauze. Collect the cell pellets and break it by acid-washed 0.5 mm glass beads.
      The expression of recombinant Pichia strains was detected by SDS-PAGE and Western
      analysis with a polyclonal serum which showed a specific protein band of 60kD.
      Theses results indicates that the recombinant VP60 produced in Pichia was
      antigenically similar to the viral polypeptide. Electron microscopic observation
      of the recombinant Pichia-derived protein revealed the presence of virus-like
      particles similar in size and appearance to native virus capsids. In the
      haemagglutination test, the recombinant VLPs, like the native RHDV, also
      agglutinated human blood type O erythrocytes and could be inhibited by the anti
      RHDV polyclonal serum.

PMID- 15859344
TI  - [Cloning of ACA gene promoter and preliminary study of its function].
AB  - Using total DNA isolated from Amaranthus caudatus as the template, a DNA fragment
      of about 700bp upstream of the coding sequence of Amaranthus caudatus agglutinin
      (ACA) gene was amplified by TAIL-PCR and cloned. To examine the regulatory
      function of this DNA fragment, it was inserted into a plant expression vector
      containing GUS gene to substitute the CaMV 35S promoter and the resulted
      recombinant plasmid was designated as pBpAG. The expression vector pBpAG was
      transferred to different tissues of plants, via Agrobacterium-mediated
      transformation in vacuum condition. Transient expression of GUS in the
      transformed tissues was detected by histochemical GUS staining and the results
      showed that the GUS activity was expressed specifically in seeds. These
      preliminary results indicate that this DNA fragment upstream of the ACA coding
      sequence could very possibly be a promoter with seed specificity. Some putative
      cis-elements within the promoter were discussed.

PMID- 15859345
TI  - [Isolation of the capsid protein gene of maize dwarf mosaic virus and its
      transformation in maize].
AB  - The MDMV (Maize Dwarf Mosaic Virus, MDMV) CP (Coat Protein, CP) gene was cloned
      by RT-PCR method and introduced into the embryonic calli derived from immature
      embryos of elite inbred 18-599hong and 18-599bai via particle bombardment.
      Bombarded calli were selected on selection medium containing 5-10 mg/L (PPT)
      Bialaphos. From resistant calli, 79 plantlets were regenerated. 18 of 79 were
      grown and harvested. The results of Southern blotting and PCR analysis
      demonstrated that MDMV CP have been integrated into the genome of the transgenic
      plants. PCR-positive progeny plants were artificially inoculated with MDMV strain
      B, and the average chlorosis of the functional leaves of each plant was
      investigated. The typical symptoms were observed from the leaves of the control
      inbreds. while, the presence of the MDMV CP gene provided resistance to
      inoculation with MDMV strain B.

PMID- 15859346
TI  - [Study on cloning of sisomicin-resistant gene (sisR) from Micromonospora
      inyoensis].
AB  - A new sisomicin resistance gene sisR was cloned from sisomicin-producing
      Micromonospora inyoensis. The sisR fragment was obtained by PCR amplification.
      The primer pairs were designed based on grm gene sequence from gentamicin
      producing Micromonospora purpurea. The template DNA was isolated from
      Micromonospora inyoensis. A series of different DNA fragments were amplified by
      PCR, which were sub-cloned to vector pUC19 for further identification. It was
      found that five specific transformants containing target DNA fragments could
      resist high concentrations of sisomicin (over 1000 microg/mL sisomicin). One of
      them designated as sisR, was then sequenced and the alignment among sisR and
      other related genes showed that sisR gene differs from any known genes. It was
      concluded that sisR gene is a sequence that has not been reported so far.

PMID- 15859347
TI  - [GFP reporter gene under the direction of chicken ovalbumin gene promoter
      expressed in the CHO cell and in the primary cell cultures of chicken oviduct].
AB  - To reseach GFP reporter gene under the control of chick ovalbumin gene regulatory
      elements express in the CHO cell and in the primary cell cultures of chicken
      oviduct. 1.5kb fragment and 2.9kb fragment were amplicated by PCR method, two
      fragments were subeloned to manmalian expression vector pGFP-N2 by recombinant
      DNA technology, the CMV promoter was cut off from pGFP-N2, so two expression
      vectors were constructed, one is the P2.9koval-GFP including promoter, first
      exon, first intron of chicken ovalbumin gene, the other is the P1.5koval-GFP
      including first intron of chicken ovalbumin gene. Restriction enzyme digestion
      and DNA sequence analysis revealed that 5'upstream regions of ovalbumin gene were
      not only identical to those of the published chicken ovalbumin gene, but also
      were contained in the recombinant vector. They were transfected into the CHO cell
      and the primary cell cultures of chicken oviduct by Lipofectin, they were used
      for fluorescence detection. GFP protein existed in GFP transfected the CHO cell
      and the primary cell cultures of chicken oviduct. It is demonstrated that GFP
      reporter gene under the direction of chick ovalbumin gene promoter could be
      expressed in the CHO cell and in the primary cell cultures of chicken oviduct.

PMID- 15859348
TI  - [Generation of transgenic mice for hygromycin and neomycin resistance genes and
      studies on transgene expression].
AB  - To generate transgenic mice in which both hygromycin (hyg) and neomycin (neo)
      resistance genes are expressed in murine fibroblast cells (MEFs), which are
      required for conditional gene knock-out and screening of drug resistant ES cell
      clones. To construct HygR-neoR expression vector, pTK-hygR-pA and PGK-neoR-pA
      were cloned into pBluescript vector. DNA fragments of tandem genes ( 4245bp )
      were prepared by Kpn I and Xba I digestion and transgene was microinjected into
      pronucleus of zygotes to generate transgenic mice. Transgenic mice were
      identified by PCR and Southern blot; expression of hygR and neoR gene transcripts
      were detected by RT-PCR. 7 founder mice carrying hyg-neo resistant genes were
      obtained and 6 transgenic mouse lines were successfully established. The hygR and
      neoR gene transcripts were detected in the liver and/or ovary of transgenic mice
      from hn30, hn33, hn66 and hn67 mouse lines. In MEFs isolated from the mice of
      line hn66 and hn30, expression of hyg and neo resistant genes was also
      detectable. Transgenic mouse lines expressing two anti-drug genes have been
      established. The hyg and neo resistant gene transcripts were detected in the MEFs
      of two transgenic mouse lines.

PMID- 15859349
TI  - [High expression of the foot-and-mouth disease's structural protein P1 in
      Escherichia coli and analysis of its biology activity].
AB  - Foot-and-mouth disease virus (FMDV) is the aetiological angent of a highly
      contagious viral disease. The complete gene encoding the structural protein of
      FMDV (P1) was subcloned into expression vector pGEX-KG, resulting in the fusion
      expression plasmid pKG-P1. After transformed into E. coli BL21(DE3) and induced
      by IPTG, the results of SDS-PAGE showed that the GST-P1 fusion protein was
      expressed in high level. The molecular weight of the fusion protein wa 110kD and
      the expressed products were soluble. Western-blotting was performed to confirm
      that the expressed fusion protein could specifically react with antiserum against
      FMDV. The fusion proteins were further purified by GST purification kit and an
      indirect ELISA (P1-ELISA) based on the purified proteins was developed.
      Comparison between P1-ELISA and the standard indirect haemagglutinin assay showed
      the two methods had 87 per cent agreement by detecting 864 serum samples,
      indicating the purified P1 protein was specific as the antigen of indirect P1
      ELISA.

PMID- 15859350
TI  - [Construction of flocculation selective vector and expression of beta-glucosidase
      gene in Saccharomyces cerevisiae].
AB  - Selective markers used in yeast vector for gene manipulation were usually drug
      resistance or autotrophy. Unfortunately, drug resistance selective marker
      requires drug sensitive host and most industrial strains were not autotrophy. In
      this paper, flocculation gene (FLO1) from Saccharomyces cerevisiae ABXL-1D was
      amplified by PCR, sequenced and cloned to construct an expression vector. The new
      vector was easy to manipulate and suitable for broad host of yeasts without
      either autotrophy or drugs. beta-glucosidase gene from Bacillus polymyxa was
      cloned with the vector and expressed in Saccharomyces cerevisiae. The specific
      activity of beta-glucosidase of the recombinant yeast cell-free extract was 3.91
      u/mg protein. The residue glucose of the recombinant yeast was considerably
      reduced in mixed fermentation of glucose and cellobiose. It should be favorable
      for ethanol fermentation when utilize lignocellulosic biomass as raw material.

PMID- 15859351
TI  - A new mouse model for infantile neuroaxonal dystrophy, inad mouse, maps to mouse
      chromosome 1.
AB  - Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive hereditary
      neurodegenerative disease of humans. So far, no responsible gene has been cloned
      or mapped to any chromosome. For chromosome mapping and positional cloning of the
      responsible gene, establishment of an animal model would be useful. Here we
      describe a new mouse model for INAD, named inad mouse. In this mouse, the
      phenotype is inherited in an autosomal recessive manner, symptoms occur in the
      infantile period, and the mouse dies before sexual maturity. Axonal dystrophic
      change appearing as spheroid bodies in central and peripheral nervous system was
      observed. These features more closely resembled human INAD than did those of the
      gad mouse, the traditional mouse model for INAD. Linkage analysis linked the inad
      gene to mouse Chromosome 1, with the highest LOD score (=128.6) at the D1Mit45
      marker, and haplotype study localized the inad gene to a 7.5-Mb region between
      D1Mit84 and D1Mit25. In this linkage area some 60 genes exist: Mutation of one of
      these 60 genes is likely responsible for the inad mouse phenotype. Our
      preliminary mutation analysis in 15 genes examining the nucleotide sequence of
      exons of these genes did not find any sequence difference between inad mouse and
      C57BL/6 mouse.

PMID- 15859352
TI  - Identification and characterization of a new Down syndrome model,
      Ts[Rb(12.1716)]2Cje, resulting from a spontaneous Robertsonian fusion between
      T(171)65Dn and mouse chromosome 12.
AB  - The segmental trisomy model, Ts65Dn, has been a valuable resource for the study
      of the molecular and developmental processes associated with the pathogenesis of
      Down syndrome. However, male infertility and poor transmission of the small
      marker chromosome, T(17(16))65Dn, carrying the distal end of mouse Chromosome 16
      (MMU16) are limiting factors in the efficient production of these animals for
      experimental purposes. We describe here the identification and preliminary
      characterization of mice, designated Ts[Rb(12.17(16))]2Cje, carrying a
      chromosomal rearrangement of the Ts65Dn genome whereby the marker chromosome has
      been translocated to Chromosome 12 (MMU12) forming a Robertsonian chromosome.
      This stable rearrangement confers fertility in males and increases the frequency
      of transmitted segmental trisomy through the female germline. We confirm
      retention of a dosage imbalance of human Chromosome 21 (HSA21)-homologous genes
      from App to the telomere and expression levels similar to Ts65Dn within the
      triplicated region. In addition, we characterized the dendritic morphology of
      granule cells in the fascia dentata in Ts[Rb(12.17(16))2Cje and 2N control mice.
      Quantitative confocal microscopy revealed decreased spine density on the
      dendrites of dentate granule cells and significantly enlarged dendritic spines
      affecting the entire population in Ts[Rb(12.17(16))]2Cje as compared to 2N
      controls. These findings document that the structural dendritic spine
      abnormalities are similar to those previously observed in Ts65Dn mice. We
      conclude that this new model of Down syndrome offers reproductive advantages
      without sacrificing the integrity of the Ts65Dn model.

PMID- 15859353
TI  - Comparative genomic analysis reveals a distant liver enhancer upstream of the
      COUP-TFII gene.
AB  - COUP-TFII is a central nuclear hormone receptor that tightly regulates the
      expression of numerous target lipid metabolism genes in vertebrates. However, it
      remains unclear how COUP-TFII itself is transcriptionally controlled since
      studies with its promoter and upstream region fail to recapitulate the gene's
      liver expression. In an attempt to identify liver enhancers in the vicinity of
      COUP-TFII, we employed a comparative genomic approach. Initial comparisons
      between humans and mice of the 3470-kb gene-poor region surrounding COUP-TFII
      revealed 2023 conserved noncoding elements. To prioritize a subset of these
      elements for functional studies, we performed further genomic comparisons with
      the orthologous pufferfish (Fugu rubripes) locus and uncovered two anciently
      conserved noncoding sequences (CNS) upstream of COUP-TFII (CNS-62kb and CNS
      66kb). Testing these two elements using reporter constructs in liver cells
      (HepG2) revealed that CNS-66kb, but not CNS-62kb, yielded robust in vitro
      enhancer activity. In addition, an in vivo reporter assay using naked DNA
      transfer with CNS-66kb linked to luciferase displayed strong reproducible liver
      expression in adult mice, further supporting its role as a liver enhancer.
      Together, these studies further support the utility of comparative genomics to
      uncover gene regulatory sequences based on evolutionary conservation and provide
      the substrates to better understand the regulation and expression of COUP-TFII.

PMID- 15859354
TI  - Quantitative trait loci analysis of heat stress resistance of spermatocytes in
      the MRL/MpJ mouse.
AB  - The MRL/MpJ mouse has previously been reported to possess an interesting
      phenotype in which spermatocytes are resistant to the abdominal temperature heat
      shock. In this study genetic analysis for it was performed. The phenotypes of F2
      progenies produced by mating MRL/MpJ and control strain C57BL/6 mice were not
      segregated into two types as parental phenotypes, suggesting that the phenotype
      is controlled by multiple genetic loci. Thus, quantitative trait loci (QTL)
      analysis was performed using 98 microsatellite markers. The weight ratio of the
      cryptorchid testis to the intact testis (testis weight ratio) and the Sertoli
      cell index were used for quantitative traits. QTL analysis revealed two
      significant QTLs located on Chrs 1 and 11 for testis weight ratio and one
      significant QTL located in the same region of Chr 1 for the Sertoli cell index. A
      microsatellite marker locus located in the peak of the QTL on Chr 1 did not
      recombine with the exonuclease 1 (Exo1) gene locus in 140 F2 progenies. Mutation
      of the Exo1 gene was previously reported to be responsible for metaphase-specific
      apoptosis (MSA) of spermatocytes in the MRL/MpJ mouse. These results raise the
      possibility that mutation of the Exo1 gene is responsible for both MSA and heat
      stress resistance of spermatocytes in the MRL/MpJ mouse.

PMID- 15859355
TI  - Transcripts associated with Prdx6 (peroxiredoxin 6) and related genes in mouse.
AB  - PRDX6 is a cytosolic member of the peroxiredoxin family of antioxidant proteins,
      which protect cells from oxidative damage by reducing cellular peroxides.
      Knockout studies and transgenic overexpression of Prdx6 in mice have demonstrated
      an important role for this protein in the defense against oxidative stress. Using
      Northern blotting with various Prdx6 probes, we have revealed the existence of
      multiple transcripts with distinct tissue distributions and regulation, including
      the major 1.4-kb transcript highly expressed in liver and lung, and two
      additional transcripts expressed primarily in liver. We hypothesized that these
      additional transcripts correspond either to alternative Prdx6 mRNAs or to highly
      related genes such as the intronless genes Aop2-rs1 and Aop2-rs2. A combination
      of Northern blotting, RACE, and EST and genomic sequence analysis has determined
      that all three liver transcripts are derived from the Prdx6 gene, as they are
      absent in Prdx6-null mice and differ in their 3' UTRs, suggesting the utilization
      of different transcription termination signal sequences which we have identified
      by sequence analysis. We found the Aop2-rs1 gene to be exclusively expressed in
      testis as a 1.2-kb transcript and have identified putative regulatory elements in
      its promoter. In contrast, Aop2-rs2 appears not to be expressed in any tissues,
      although we have evidence for the existence of other related genes that are
      expressed in a tissue-specific manner. Since the Prdx6 transcripts exhibit
      differential regulation in response to growth and oxidative stress, further
      investigation may reveal their distinct roles in the cell and mechanism of
      regulation.

PMID- 15859356
TI  - Marker-assisted introgression of trypanotolerance QTL in mice.
AB  - A marker-assisted introgression (MAI) experiment was conducted to use genetic
      markers to transfer each of the three trypanotolerance QTL from a donor mouse
      strain, C57BL/6, into a recipient mouse strain, A/J. We used a backcross strategy
      that consisted of selecting two lines, each carrying two of the donor QTL alleles
      through the backcross (BC) phase. At the fourth BC generation, single-carrier
      animals were selected for the production of homozygous animal in the intercross
      phase. The QTL regions (QTLR) were located on chromosomes MMU1, MMU5, and MMU17.
      Groups of mice with different genotypes and the parental lines were subjected to
      a challenge with Trypanosoma congolense. The results show that trypanotolerance
      QTL was successfully moved into the recipient background genotype, yielding a
      longer survival time. The mean estimated survival time was 57.9, 49.5, and 46.8
      days for groups of mice carrying the donor QTL on MMU1, MMU5, and MMU17 on A/J
      background. The mean estimated survival time was 29.7 days for the susceptible
      A/J line and 68.8 days for the resistant C57BL/6 line. The estimated QTLR effects
      are close to 30% smaller than those in the original mapping population which was
      likely caused by the difference in the background on which the effects of QTLR
      are tested. This is the first report of successful marker-assisted introgression
      of QTL in animals. It is experimental proof of the use of genetic markers for
      marker-assisted introgression in animal breeding.

PMID- 15859357
TI  - Modifiers of mammary tumor progression and metastasis on mouse chromosomes 7, 9,
      and 17.
AB  - Tumor progression, the growth and dissemination of primary tumor to secondary
      sites, is of critical clinical importance since the vast majority of patients
      succumb to metastatic disease rather than to the primary tumor. Many factors are
      likely to influence this process, including the primary oncogenic events,
      environmental exposures and stress and progressive stochastic mutations.
      Previously, our laboratory demonstrated that an additional factor, the genetic
      background on which tumors arose, had a significant effect on metastatic
      efficiency. Using a highly metastatic transgene-induced mammary tumor model, a
      locus modulating metastatic efficiency, Mtes1, was localized on proximal mouse
      Chromosome 19. In addition, a number of additional suggestive loci were observed
      on several other chromosomes. To confirm the presence of these additional loci
      before initiating cloning strategies, chromosomal substitution strains have been
      constructed and assayed for modification of the cancer phenotypes. Using the
      chromosomal substitution strains, an additional modifier modulating tumor latency
      was confirmed, as well as three new modifier genes that alter the kinetics of
      tumor progression. Identification and analysis of these loci will likely present
      interesting and novel information about cancer heterogeneity in the human
      population.

PMID- 15859359
TI  - Side effects from polydioxanone.
AB  - It is the first case reported of delay hypersensitivity due to polydioxanone (PDS
      II).

PMID- 15859358
TI  - Increased plasticity of genomic imprinting of Dlk1 in brain is due to genetic and
      epigenetic factors.
AB  - The expression of six imprinted genes (Dlk1, Gt12, Igf2r, Kcnq1, Nnat, and Peg1)
      was examined in brains of 21 mice derived from N2 x N2 intercrosses between
      C57BL/6 and MOLF/Ei strains. Imprinting of Igf2r, Kcnq1, Gt12, and Dlk1 varied
      among individuals. As three of these genes are implicated in cell-cell signaling
      or cell-environment interactions, variation in their imprinting may influence a
      wide range of biological processes from cell differentiation to behavior. To
      elucidate the mechanisms underlying the interindividual imprinting variation in
      the brain, we focused our effort on the paternally expressed gene Dlk1. We
      investigated expression of Dlk1 in the brains of animals from N9 and N10
      backcrosses and found that reactivation of the normally silent maternal Dlk1
      allele in the N9 and N10 mice occurred less often than in N2 x N2 animals. Our
      data suggest that trans-acting genetic factors of MOLF/Ei origin facilitate the
      reactivation of the normally silent maternal allele of Dlk1. We mapped one of
      these factors to the proximal part of Chr 7. The results of bisulfite sequencing
      methylation analysis show that reactivation of the maternal allele was also
      associated with hypermethylation of the intragenic differentially methylated
      region (IG DMR), which is the imprinting control region for the Dlk1-Gt12 domain.
      Thus, the imprinting status of Dlk1 in the brain depends upon trans-acting
      genetic influences and correlates with the methylation status of a specific
      subregion of the IG DMR.

PMID- 15859360
TI  - Influence of ethinyl estradiol on C1s inhibitor: a new etiopathogenetic mechanism
      of angioedema. Case report.

PMID- 15859361
TI  - Safety of celecoxib in patients with adverse skin reactions to acetaminophen
      (paracetamol) and nimesulide associated or not with common non-steroidal anti
      inflammatory drugs.
AB  - BACKGROUND: Acetaminophen (paracetamol--P) and Nimesulide (N) are widely used
      analgesic-antipyretic/anti-inflammatory drugs. The rate of adverse
      hypersensitivity reactions to these agents is generally low. On the contrary non
      steroidal anti-inflammatory drugs (NSAIDs) are commonly involved in such
      reactions. Celecoxib (CE) is a novel drug, with high selectivity and affinity for
      COX-2 enzyme. OBJECTIVE: We evaluated the tolerability of CE in a group of
      patients with documented history of adverse cutaneous reactions to P and N
      associated or not to classic NSAIDs. METHODS: We studied 9 patients with
      hypersensitivity to P and N with or without associated reactions to classic
      NSAIDs. The diagnosis of P and N-induced skin reactions was based in vivo
      challenge. The placebo was blindly administered at the beginning of each
      challenge. After three days, a cumulative dosage of 200 mg of CE in refracted
      doses were given. After 2-3 days, a single dose of 200 mg was administered. All
      patients were observed for 6 hours after each challenge, and controlled again
      after 24 hours to exclude delayed reactions. The challenge was considered
      positive if one or more of the following appeared: erythema, rush or urticaria
      angioedema. RESULTS: No reaction was observed with placebo and eight patients
      (88.8%) tolerated CE. Only one patient developed a moderate angioedema of the
      lips. CONCLUSION: Only one hypersensitivity reaction to CE was documented among 9
      P and N-highly NSAIDs intolerant patients. Thus, we conclude that CE is a
      reasonably safe alternative to be used in subjects who do not tolerate P and N.

PMID- 15859362
TI  - Prevalence of peanut sensitization in a population of 4,737 subjects--an Allergo
      Vigilance Network enquiry carried out in 2002.
AB  - A total of 4,737 people consulting allergologists were routinely tested for
      peanut sensitization. The study involved 84 allergologists in the Allergo
      Vigilance Network over a period of 30-60 consecutive days. Investigation
      procedures were identical. Results classified subjects into four groups according
      to the clinical history and prick-tests to common inhalants: group 1: subjects
      suspected of having a food allergy; group 2: subjects with ongoing atopic
      disease; group 3: subjects with an underlying predisposition to atopy, as showed
      by one or more positive results to prick-tests with airborne allergens; group 4:
      non atopic subjects. The sensitization rates were 22.7%, 8.7%, 4%, and 0.4%
      respectively. Assuming that 25% of the French population is allergic the rate of
      sensitization to peanut in the general population should be between 1% and 2.5%.
      Considering a ratio of 3.3 between sensitization and clinical allergy as
      plausible, the prevalence of peanut allergy could be 0.3% to 0.75% of the French
      population. This figure is lower than that for the UK, the US and Canada (0.8% to
      1.5%). The correlation between the data in this study and those from previous
      epidemiological studies validates the methodology used in this type of enquiry.
      One of the aims of the Allergo-Vigilance Network set up in 2001 is to collect
      data from a large number of people. We present here the results of a study
      carried out in 2002 by 84 allergologists in the Allergo-Vigilance Network. The
      primary aim was to assess the prevalence of peanut sensitization in the French
      population seeking treatment for various allergic disorders. The second objective
      was to determine whether there was any difference in risk of peanut sensitization
      in people with ongoing atopic disease, in those with an underlying predisposition
      to atopy (shown by positive prick-tests) and finally in non atopic people.

PMID- 15859363
TI  - Physical exercise does not favour adverse reactions to allergen immunotherapy by
      the sublingual route.
AB  - It is generally recommended in consensus documents on allergen immunotherapy to
      avoid any kind of physical exercise in the 24 hours following the administration
      of the allergen extract but such recommendation is not supported by scientific
      evidence. We evaluated the risk of developing adverse reactions in a group of
      patients submitted to sublingual immunotherapy by performing a controlled
      exercise test. Eleven patients were included in the study, 8 treated with grass
      pollen and 3 with Parietaria pollen extract by Staloral300 (Stallergenes, Antony,
      France), with the build-up phase in 11 days suggested by the manufacturer and a
      top dose of 300 IR. At the first maintenance dose, in all patients were measured
      heart rate, blood pressure, FEV1, and tryptase in blood. Then the maintenance
      dose was assumed and the physical exercise performed by cycloergometer
      maintaining a heart rate around 100 b/min and measuring again tryptase, blood
      pressure and FEV1. The results showed that no patient had adverse reaction
      following physical exercise, neither showed significant changes in FEV1, blood
      pressure, or tryptase level, which was 5.57 +/- 4.54 mcg/l before and 5.81 +/-
      4.34 mcg/l after exercise. This suggests that there is no reason to advise
      against physical exercise, and particularly sporting activity, in patients
      treated with sublingual immunotherapy thus avoiding to interfere with the
      subject's lifestyle and consequently with his quality of life.

PMID- 15859364
TI  - Acute recurrent otalgia and food allergy: a case report and review of the
      literature.

PMID- 15859365
TI  - Estimation of interleukin-6 level in psoriasis patients.

PMID- 15859366
TI  - Anaphylactic shock to Argas reflexus bite.
AB  - Anaphylaxis is a severe, life-threatening allergic reaction, affecting both
      children and adults. The occurrence of anaphylaxis is not as rare as generally
      believed (1.21% to 15.04% of the US population). Often the cause of this reaction
      remain unknown, mainly due to the difficulty in defining the outbreaking causes.
      Herein, we describe an interesting case of a patient, who developed an
      anaphylactic reaction after the bite of a pigeon tick. During the last 2 years,
      in wintertime, the patient often came to the emergency room for general rash and
      swelling, hypotension and tachycardia preceded by itching and general distress.
      Notably, the symptoms manifested themselves as night fell. In two particular
      occasions the patient reached the hospital in a state of shock. After another
      episode of general swelling, the patient was invited to examine her domestic
      environment. She brought us some parasites, collected at home, particularly on
      the bed. A morphological examination by entomologists proved these parasites to
      belong to Argas reflexus (Arg.r.), one of the 31 species of soft ticks. The
      presence of specific IgE to a protein secreted by the Arg.r. salivary glands was
      in favour of immediate-type systemic reaction, as supposed by the clinical
      history.

PMID- 15859368
TI  - Lessons regarding the IgE system.

PMID- 15859367
TI  - Comparison of allergen immunotherapy and drug treatment in seasonal
      rhinoconjunctivitis: a 3-years study.
AB  - Drug treatment and specific immunotherapy (SIT) are both effective in seasonal
      rhinoconjunctivitis, but the former acts only on allergic symptoms while the
      latter modifies the natural history of the disease. Only a few studies compared
      the clinical efficacy of the two treatments with contrasting results. We planned
      a study to compare the efficacy of SIT (15 patients) and drug treatment (15
      patients) in moderate to severe seasonal rhinoconjunctivitis caused by
      sensitization to grass pollen. SIT was performed by a 5-grass extract
      standardized in IR and absorbed onto calcium phosphate (Phostal, Stallergenes,
      Antony, France) using the conventional build-up phase in 12 weeks and a
      maintenance treatment with monthly injection for three years. Drug treatment was
      done with cetirizine as antihistamine, mometasone furoate as nasal topical
      steroid, and levocabastine eyedrops. All patients registered during the pollen
      season their symptoms and drug consumption. After one year 12 of 15 patients
      treated with SIT had less symptoms and drug consumption in respect to baseline
      compared to none in drug treated group (p = 0.021) and after three years 15 of 15
      were improved in group A compared to one of 15 in group B (p = 0.008). These
      findings indicate an higher efficacy of SIT in patients with seasonal rhinitis
      not only in the long term but also in the first year of treatment.

PMID- 15859369
TI  - Transvestic fetishism in the general population: prevalence and correlates.
AB  - We used a random sample of 2,450 18-60 year-olds in the general population of
      Sweden to study the prevalence as well as the social, sexual, and health
      correlates of transvestic fetishism (sexual arousal from cross-dressing). Almost
      three percent (2.8%) of men and 0.4% of women reported at least one episode of
      transvestic fetishism. Separation from parents, same-sex sexual experiences,
      being easily sexually aroused, pornography use, and higher masturbation frequency
      were significantly associated with transvestic fetishism. A positive attitude to
      this sexual practice and paraphilia indicators--sexual arousal from using pain,
      exposing genitals to a stranger, and spying on others having sex--were
      particularly strong correlates to the dependent variable.

PMID- 15859370
TI  - Psychiatric and characterological factors relevant to excess mortality in a long
      term cohort of prostitute women.
AB  - We previously reported on the causes of death in a 30-year open cohort of 1,969
      prostitute women. Excess mortality was mostly accounted for by homicide, suicide,
      drug and alcohol toxicity, and AIDS, with AIDS deaths occurring in prostitutes
      identified as injecting drug users. Presently, we examine observed mortality
      trends in light of the literature on personality and psychopathological
      characteristics reported for prostitute women, and with reports linking such
      personality characteristics to excess mortality. We observed consistency between
      the observed pattern of mortality in prostitute women and mortality that would be
      expected in a sample of persons at high risk for antisocial and borderline
      personality disorder.

PMID- 15859371
TI  - Fluoxetine-induced changes in tactile sensation and sexual functioning among
      clinically depressed women.
AB  - Sexual side effects resulting from serotonin specific reuptake inhibitors (SSRIs)
      use may be mediated by a number of peripheral mechanisms, including alterations
      in tactile sensitivity. It was hypothesized that sexual difficulties resulting
      from SSRI use arise in part from an over-sensitivity or under-sensitivity of
      tactile sensation. Tactile sensitivity was examined on the index finger and lower
      lip in clinically depressed women at baseline (pre-medication), week 1, week 4,
      and week 8 of drug treatment (fluoxetine group n = 12, control n = 13). Analyses
      indicated that fluoxetine treatment resulted in decreased orgasm functioning.
      Fluoxetine-induced sexual changes were not mediated by tactile sensation. An
      independent association was found between sexual arousal functioning and finger
      sensation. Novel to this study, an independent association was found between
      sexual desire and finger sensation.

PMID- 15859372
TI  - Anodyspareunia in men who have sex with men: prevalence, predictors, consequences
      and the development of DSM diagnostic criteria.
AB  - In a sample of men who have sex with men (N = 404), 55 (14%) experienced
      anodyspareunia, frequent and severe pain during receptive anal sex. Most men with
      anodyspareunia described their pain as life-long, experienced psychological
      distress as a result, and avoided anal sex for periods of time. Men with
      anodyspareunia reported that psychological factors were the primary contributing
      cause of their pain. The findings contradict the myth that pain is a necessary
      consequence of receptive anal sex and show that anodyspareunia is similar to
      dyspareunia in women in terms of prevalence, mental health consequences, and
      contributing factors. Clinical criteria were developed to assist clinicians in
      diagnosing anodyspareunia.

PMID- 15859373
TI  - What is love anyway?
AB  - This essay explores seven interlocking meanings of the term love. These meanings
      are the author's synthesis based on years of trying to understand what people
      mean by the word and why they are not more explicit in explaining themselves
      during psychotherapy. The meanings may help clinicians better grasp what seems to
      be the most basic context for understanding a person's sexual life. Love may be:
      a complex emotion--it is never a single feeling; an ambition; moral commitment; a
      private dynamic struggle; a deal; a stop sign to psychological inquiry. Many
      forces in culture and within individuals resist careful scrutiny of what we mean
      by love.

PMID- 15859374
TI  - Outcome measurement in female sexual dysfunction clinical trials: review and
      recommendations.
AB  - Defining and measuring Female Sexual Dysfunction (FSD) is a complex and
      challenging task. Several factors have confounded the theory and measurement of
      FSD including: the use of an inappropriate male paradigm; difficulty in capturing
      the complexity of women's sexual response; an evolving but presently untested
      nosology; and the relative independence between subjective and objective aspects
      of women's sexual response. Each of these factors have contributed to the
      difficulty in developing meaningful and valid endpoints for clinical trials. The
      Food and Drug Administration's (FDA) 2000 draft guidance document for female
      sexual dysfunction clinical trials recommended the use of daily diary measures as
      primary and self-administered questionnaires (SAQs) as secondary endpoints. Event
      logs or diary measures may be adequate for assessing aspects of male sexual
      performance (e.g., erectile function), or in other therapeutic areas with
      discrete and readily observable endpoints (e.g., incontinence). However,
      psychometric theory suggests that for female sexual dysfunction clinical trials,
      SAQ instruments may provide more sensitive and reliable measures of outcome. We
      offer an alternative set of recommendations in the hope that the FDA will
      reconsider its position and to serve as potential guidelines for non-industry
      sponsored research on female sexuality as well. First, we propose that SAQs be
      elevated from their current status as secondary endpoints to be considered as
      potential primary endpoints in clinical trials of FSD. Second, we recommend that
      depending on the trial design and intervention under study, either an SAQ or
      diary measure (typically one or the other, and not both), might serve as a
      primary endpoint in a clinical trial. Third, SAQs and diaries should be employed,
      analyzed and interpreted in their particular areas of strength. Diaries are most
      useful for enumerating events and/or counting frequencies. SAQs are superior at
      gathering subjective data related to women's sexual function. Fourth, we believe
      there is a theoretical basis for considering SAQs to be superior measurement
      tools compared to diaries in assessing sexual dysfunction in women. At present,
      however there is insufficient objective data to fully support this opinion.
      Conversely, we do not anticipate either theoretical or objective evidence to
      support the alternative hypothesis (that diaries are superior to SAQs). If this
      proves to be correct in the future, diary measures may no longer be considered as
      primary endpoints for FSD clinical trials. Finally, we recommend that the FDA
      and/or other regulatory agencies reconsider the emphasis given to the number of
      successful or satisfactory sexual events over time as primary endpoints because
      they do not definitively demonstrate whether there has or has not been any
      improvement in the FSD endpoint under study (e.g., sexual desire). Successful and
      satisfactory encounters represent an amalgam of subjective assessments that are
      too far removed from the essential FSD component.

PMID- 15859375
TI  - A framework for change.

PMID- 15859376
TI  - Strength in numbers. Midwives in Devon have embraced the midwifery group practice
      approach to facilitate normal and home birth.

PMID- 15859377
TI  - The calm before the storm.

PMID- 15859378
TI  - Home from home.

PMID- 15859379
TI  - Spreading some magic.

PMID- 15859380
TI  - The birth of Nuno.

PMID- 15859381
TI  - An extra pair of hands.

PMID- 15859382
TI  - Home birth: a social process, not a medical crisis.

PMID- 15859383
TI  - Specialist posts for specialist needs.

PMID- 15859384
TI  - The teenage pregnancy midwives.

PMID- 15859385
TI  - Nutrition and the wisdom of craving.

PMID- 15859386
TI  - Postnatal emotional wellbeing.

PMID- 15859387
TI  - Childbirth expectations and influences.

PMID- 15859388
TI  - Stork talk.

PMID- 15859389
TI  - [The framing effect: medical implications].
AB  - Over the last 20 years, many studies explored how the way information is
      presented modifies choices. This sort of effect, referred to as "framing
      effects", typically consists of the inversion of choices when presenting
      structurally identical decision problems in different ways. It is a common
      assumption that physicians are unaffected (or less affected) by the surface
      description of a decision problem, because they are formally trained in medical
      decision making. However, several studies showed that framing effects occur even
      in the medical field. The complexity and variability of these effects are
      remarkable, making it necessary to distinguish among different framing effects,
      depending on whether the effect is obtained by modifying adjectives (attribute
      framing), goals of a behavior (goal framing), or the probability of an outcome
      (risky choice framing). A further reason for the high variability of the framing
      effects seems to be the domain of the decision problem, with different effects
      occurring in prevention decisions, disease-detection decisions, and treatment
      decisions. The present work reviews the studies on framing effects, in order to
      summarize them and clarify their possible role in medical decision making.

PMID- 15859390
TI  - [Hepatitis C virus-associated and metabolic steatosis. Different or overlapping
      diseases?].
AB  - Hepatic steatosis is the hallmark of nonalcoholic fatty liver disease (NAFLD),
      which is the consequence of multiple metabolic derangements among which insulin
      resistance plays a pivotal role. Steatosis is, also, a feature of hepatitis C
      virus (HCV) infection. However, in chronic hepatitis C, the prevalence of
      steatosis is 2.5-fold more elevated than that expected by a chance concurrence
      with NAFLD, suggesting that HCV may be implied in the development of steatosis.
      As observed in NAFLD, in patients infected with HCV genotype 1 steatosis is
      associated with an increased body mass index. On the other hand, in patients
      infected with genotype 3 the extent of steatosis strictly correlates with the
      viral load indicating that steatosis is mainly "virus-related". Regardless of the
      "metabolic" or "viral" etiology, hepatic steatosis in HCV contributes to the
      progression of liver fibrosis, to the development of hepatocellular carcinoma and
      to an impaired response to interferon treatment. Features such as obesity,
      insulin resistance and type 2 diabetes mellitus are shared by NAFLD and HCV
      associated steatosis. In addition, HCV infection, directly or through steatosis,
      favors the development of type 2 diabetes mellitus. Hyperlipidemia is an
      independent predictor of the development of NAFLD, but not of HCV-associated
      steatosis. Arterial hypertension is common in nonalcoholic steatohepatitis
      patients, and HCV infection has recently been acknowledged as an independent risk
      factor for atherosclerosis. The role of iron in the progression of both NAFLD and
      HCV-associated steatosis remains controversial while lipoperoxidation and
      oxidative stress are pathogenic mechanisms shared by both. Some metabolic risk
      factors may be shared by both HCV-associated steatosis and NAFLD although the
      disease progression and pathophysiological background may be different.
      Preliminary data suggest that the therapeutic options for NAFLD may also be
      useful to improve HCV-associated steatosis.

PMID- 15859391
TI  - [Non-invasive analyses for the diagnosis of Helicobacter pylori infection. A
      critical review of the literature].
AB  - Helicobacter pylori (H. pylori) infection may be diagnosed by means of invasive
      techniques requiring endoscopy and biopsy (histological examination, rapid urease
      test, culture, polymerase chain reaction) and by non-invasive techniques (urea
      breath test, detection of specific antibodies in the serum or urine, detection of
      the H. pylori antigen in a stool specimen). Some non-invasive tests detect active
      infection e.g. the urea breath test and the stool antigen test and are called
      active tests. Other non-invasive tests are markers of exposure to H. pylori (e.g.
      serology or urine) but do not indicate whether active infection is ongoing and
      are called passive tests. Non-invasive tests and treatment strategies are widely
      recommended in primary care settings and the choice of the appropriate test
      depends on the pre-test probability of infection, the characteristics of the test
      being used and its cost-effectiveness. The available non-invasive tests are
      reviewed in this article.

PMID- 15859392
TI  - [Paraneoplastic syndromes: pathogenetic theories, clinical aspects and
      therapeutic approach].
AB  - Paraneoplastic syndromes are uncommon diseases with different pathogenesis and
      clinical manifestations, correlated with neoplasms but not due to the tumor,
      metastasis or other distant effects. The aim of the present article is to
      describe the main paraneoplastic syndromes (neurological, endocrine-metabolic,
      rheumatological, osteo-articular, dermatological, hematological, vascular and
      nephrological), the associated pathogenetic theories (theory of the common
      embryonal sketches, theory of reactivation of the information and autoimmune
      theory) and the most important therapeutic approaches, on the basis of the
      literature. Experimental works, reviews and clinical observations, in some cases
      still in progress, regarding the described syndromes, their pathogenesis and
      their therapeutic approach have been examined. No meta-analyses regarding
      paraneoplastic syndromes have been published in the literature. The better
      described pathogenesis is the autoimmune one, characteristic of neurological,
      nephrologic and some dermatologic syndromes, for which the clinical and
      laboratory findings have been well supported. The pathogenetic theories
      associated with the other syndromes have been correlated on the basis of the
      literature. Paraneoplastic syndromes are important because their identification
      permits an early diagnosis of tumors and rapid treatment, with a largely improved
      prognosis and life expectancy for the patient. They often represent the only
      signal of a silent neoplasm; sometimes they precede the tumor itself. More
      studies are necessary for a better definition of their clinical aspects and
      pathogenesis and to delineate standard guidelines for a diagnostic-therapeutic
      approach to these diseases.

PMID- 15859393
TI  - Screening for celiac disease in patients with autoimmune thyroid disease: from
      research studies to daily clinical practice.
AB  - Screening procedures performed in research-setting studies have shown that the
      prevalence of celiac disease in patients with autoimmune thyroid disease is
      approximately 4-15 times higher than the general population, thus suggesting that
      patients with autoimmune thyroid disease should be routinely screened for celiac
      disease. However, the performance of these screening programs has never been
      evaluated in everyday, clinical-practice setting. We invited newly diagnosed
      patients with autoimmune thyroid disease, seen at our Hospital, to participate in
      a serological screening for celiac disease. Two-hundred and thirty-one patients,
      female to male ratio 8.89:1, mean age 41.3 +/- 18.1 years, range 7.1-80.5 years
      were included. The number of diagnosed celiac disease was 0. Our results do not
      support the usefulness of a screening for celiac disease in patients with
      autoimmune thyroid disease in daily practice, despite the favorable results
      obtained in research-setting studies. Since screening is a resource-consuming
      activity, for both patients and clinicians, we suggest that a careful evaluation
      of the yield of a screening is always warranted before its adoption in the
      clinical practice.

PMID- 15859395
TI  - A catastrophic case of skin gangrene.
AB  - We describe the case of a 70-year-old male with the catastrophic antiphospholipid
      syndrome admitted for skin gangrene of the fingers. The initial diagnosis was
      antiphospholipid antibody syndrome in a patient with rheumatoid arthritis and a
      history of deep vein thrombosis of the lower limbs. Liver involvement, the
      characteristic skin gangrene, pneumonia and worsening severe renal failure were
      determinant to make the final diagnosis of catastrophic antiphospholipid syndrome
      that led the patient to death.

PMID- 15859394
TI  - [I405V polymorphism of the cholesteryl ester transfer protein gene in young and
      very old individuals].
AB  - This study was designed to analyze the prevalence of I405V polymorphism in the
      cholesteryl ester transfer protein (CETP) gene, the blood CETP concentration, the
      lipoprotein pattern and certain clinical endpoints in two populations, one of
      young and another of very old individuals. We recruited 100 healthy young adults
      (median age 31 years) and 100 very old subjects (median age 89 years) and
      analyzed their DNA for the presence of variants V and I of the CETP gene.
      Subjects with the V/V genotype had lower serum concentrations of CETP. The
      frequency of this genotype in the very old was more than double that in the young
      population. Young adults with the V/V genotype had a less atherogenic lipoprotein
      pattern [lower total and LDL cholesterol levels, lower apolipoprotein (Apo) B
      levels, and a lower Apo B/Apo A-I ratio] than those with the I/V or I/I
      genotypes. The very old subjects, particularly those with the V/V genotype, had
      larger LDL than the young adults. The prevalence of clinical endpoints was much
      lower among the very old subjects with the V/V genotype.

PMID- 15859396
TI  - [TRAPS syndrome, a rare cause of fever of unknown origin: case report and review
      of the literature].
AB  - Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an
      autosomal dominant inherited condition of periodic fever and pain. TRAPS is
      caused by mutations of the TNFRSF1A gene localized at 12p13. The gene encodes
      extracellular region of the p55 TNF-alpha receptor, resulting in impaired
      cleavage and down-regulation of the membrane expressed form of the receptor, a
      diminished shedding of potentially antagonistic soluble form of the receptor and,
      as a consequence, an unbalanced TNF-alpha action. Most affected patients are from
      northern Europe. Fever, sterile peritonitis, pleural pain, arthralgia, myalgia,
      skin rash, and/or conjunctivitis occur during the syndrome episodes; some
      patients also develop systemic amyloidosis, with some differences among patients.
      An acute-phase response occurs during the episodes. We describe a case of a 23
      year-old Moldavian woman, living in Italy presenting recurrent fever episodes
      with abdominal pain and skin rash. A biopsy showed small vessel vasculitis. The
      genetic analysis showed a TNFRSF1A gene (R92Q) mutation. In this paper we report
      also a literature review on this rare disease.

PMID- 15859397
TI  - [Hypogammaglobulinemia and thymoma (Good's syndrome): a case report and a
      literature review].
AB  - Good's syndrome is a rare adult-onset immunodeficiency disease characterized by
      hypogammaglobulinemia and thymoma. A 61-year-old male patient was diagnosed with
      Good's syndrome after a 2-year history of recurrent respiratory infections. Chest
      X-ray and chest computed tomography scan showed a mediastinal mass which was
      surgically removed. Histology revealed a thymoma. Following surgery he presented
      with recurrent respiratory and urinary tract infections and with esophageal
      candidiasis, even though his overall conditions dramatically improved after
      starting treatment with an appropriate dosage of intravenous immunoglobulins.
      Laboratory tests showed hypogammaglobulinemia, mild neutropenia, lymphopenia with
      no B cells, decreased CD4+ lymphocytes with an inverted CD4/CD8 ratio and
      increased interleukin-4-producing CD4+ lymphocytes, suggestive of an excessive
      Th2 response.

PMID- 15859398
TI  - [Trends and variation of CFC-11 in the atmosphere of Beijing].
AB  - In recent years, concentration of CFC in the atmosphere has undergone rapid
      changes especially in association with human activities. For the influence of CFC
      on climate changes and environment changes, the concentration of atmospheric CFC
      11 in Beijing is continuously observed and analyzed by a gas chromatography-mass
      spectrometry. The seasonal variation concentration and trends of CFC-11 are
      reported. The results show that the seasonal variation of CFC-11 was basically
      similar from 1999 to 2003. There was one peak value in the seasonal variation of
      CFC-11 in 1999-2003. The highest monthly average concentration of CFC-11 was
      1149.5 +/- 531.9 x 10(12) ( V x V(-1)) in summer and the lowest monthly average
      concentration of CFC-11 was 487.5 +/- 131.5 x 10(-12) (V x V(-1)) in spring. The
      annual average concentration of CFC-11 was increasing in Beijing atmosphere from
      1995 to 1998, and the average increasing ratio was 17.9%. The annual average
      concentration of CFC-11 was slowly decreasing from 1999, and the average
      decreasing ratio was 10.7%. The average concentration of CFC-11 in the atmosphere
      of Beijing was 3 to approximately 5 times of the average concentration of CFC-11
      in the atmosphere of Mauna Loa Station of U.S.A.

PMID- 15859399
TI  - [Content and distribution of fluorine in Chinese coals].
AB  - Nationwide sampling program is designed according to the resources distribution
      and coal-forming periods as well as coal rank and yield of coal in China, and 305
      coal samples were collected from 26 provinces, municipalities and autonomous
      regions. Fluorine in coal is determined by pyrohydrolysis / fluoride-ion
      selective electrode method. Fluorine in coals is mainly of an inorganic nature.
      Coal rank has no effect on fluorine content. The influence of a factor, such as
      geological age, on fluorine contents might be concealed by other factors, more
      research should be done to discern it. The distribution of fluorine in each
      province, municipality and autonomous region's coals is studied, and the fluorine
      source in coal-burning endemic fluorosis areas should be estimated over again.
      The contents of fluorine in Chinese coals show logarithm normal distribution, and
      90% of values ranged from 47mg/kg to 347mg/kg, the average fluorine content in
      Chinese coals was designated as the geometric mean, 136mg/kg. Fluorine in Chinese
      coals is within the world coal's range.

PMID- 15859400
TI  - [Emission of fluorine from black liquor coal-water slurry combustion].
AB  - The paper is about the emission of fluorine from an experimental boiler of 0.25
      MW when burning black liquor coal-water slurry (CWS). The result is compared with
      CWS. And the analysis of effect factors is also carried out. Experimental
      research show that, the content of fluorine in CWS, which was less than 30 mg/kg,
      was relatively low. The emission ratio and concentration of fluorine were 70% -
      90% and 2.0 - 2.6 mg/m3 respectively when burning common CWS; while the data of
      those when combusting black liquor CWS were 45% - 80% and 1.7 - 3.0 mg/m3
      respectively. The hearth temperature and the element of CWS were two factors of
      emission fluorine when burning CWS.

PMID- 15859401
TI  - [Evaluation of gaseous biotrickling filter transient performance for TEX
      removal].
AB  - The gaseous stream laden with toluene, ethylbenzene and the three xylenes (TEX)
      compounds is used to evaluate the transient performance of a biotrickling filter
      (BTF) that packes with the mixture of ACOF (Activated Carbon on Fiber) and
      stainless steel mesh as biological carrier. The shock loading experiment show
      that if the loading is varied within the limits of the maximum EC, when the
      loading was doubled, the removal efficiency decreased 20% in the beginning, and
      after about 2 days, it regained the original removal efficiency. The non-use
      experimental results show that short time (8-12 h) non-use had no or very little
      effect on the BTF removal efficiency. 2 days scale non-use caused a decrease of
      20% in the BTF performance, and need 4-6 h to regain the initial performance. 29
      days' non-use caused a decrease of 70%-80% in the BTF performance, and needed
      about 10 days to get recover.

PMID- 15859402
TI  - [Removal of nitric oxide from waste gas streams with hexamminecobalt solution].
AB  - Aqueous ammonia solution can be used to remove NO from waste gas streams by
      adding soluble cobalt(II) salt into aqueous ammonia solution. The
      hexamminecobalt(II) cations can not only bind nitric oxide but also activate
      oxygen molecules in aqueous solutions. Nitric oxide is absorbed and oxidized
      simultaneously in the same reactor. Nitric oxide can be turned into nitrite and
      nitrate. Activated carbon is used to catalyze the reduction of hexamminecobalt
      (III) to hexamminecobalt (II) to maintain the capability of removing NO with the
      hexamminecobalt solution. The influences of temperature and activated carbon
      particle size on the conversion of hexamminecobalt (III) are investigated.
      According to the experimental results, the catalytic reduction reaction rate
      increased with temperature. The influence of particle size of AC on the reduction
      of hexamminecobalt (III) in fixed bed reactor was very little. Oxygen in the gas
      phase was beneficial to the absorption of NO into the hexamminecobalt solution.
      The experiments performe manifestly that the hexamminecobalt solution coupled
      with catalytic regeneration of hexamminecobalt (II) was able to maintain a high
      nitric oxide removal efficiency for a long time. This method may have a bright
      promise in application.

PMID- 15859403
TI  - [Catalytic combustion of soot on combined oxide catalysts].
AB  - Combined oxide catalysts are prepared for catalytic combustion of soot and
      regeneration from diesel emissions. Thermo-gravimetric analysis(TGA) and
      temperature programmed oxidation(TPO)are used to evaluate the activity of
      catalysts under the influence of composition,atomic ration, H2O, calcinations
      temperature and mass ration between catalysts and soot. Results show that Cu-Mo-O
      had high activity among double metal oxide catalysts. Among multicomponent metal
      oxide catalysts, Cu-K-Mo-O had high activity when atomic ratio Cu: K: Mo = 1:1:2
      and mass ration between catalysts and soot equals 5: 1. Under this condition,
      soot ignition temperature of Cu-K-Mo-O catalyst was 327 degrees C. H2O addition
      and calcinations temperature had little influence on it,which is one kind of
      compatible catalyst for soot control and catalytic regeneration from diesel
      emissions.

PMID- 15859404
TI  - [Dust storms trend in the Capital Circle of China over the past 50 years and its
      correlation with temperature, precipitation and wind].
AB  - The trends of number of dust storm days of the selected 11 meteorological
      stations from their established year to 2000 as well as their correlations with
      temperature, precipitation and wind are revealed. The number of dust storm days
      of the Capital Circle of China is distinctly variable in space and time. The
      numbers of dust storm days of the western area are far more than those of the
      eastern area. The interannual variability of number of dust storm days is
      remarkable. The number of dust storm days of the following 7 stations,
      Erlianhaote, Abaga, Xilinhaote, Fengning, Zhangjiakou, Huailai and Beijing,
      declined along the past decades, but those of the other four stations had no
      significant upward or downward trends. There is a marked seasonality of the
      number of dust storm days, and the maximum was in April. The correlation between
      number of dust storm days and number of days of mean wind velocity > 5 m/s, which
      is critical wind velocity to entrain sand into the air, was strongest among the
      three climatic factor. There were significant positive correlations between the
      number of dust storm days and number of days of mean wind velocity > 5 m/s in 6
      stations. The second strongest climatic factor correlated with the number of dust
      storm days is temperature. There are significant negative correlations between
      the number of dust storm days and mean annual temperature, mean winter
      temperature, mean spring temperature in 3 or 4 stations. The correlation between
      the number of dust storm days and precipitation is weakest. Only one station,
      Zhurihe, showes significant negative correlation between the number of dust storm
      days and spring rainfall. There are 4 stations whose number of dust storm days
      don't significantly correlate with the climate. In the end, the spatial-temporal
      variability of dust storms and its relation with climate in the Capital Circle of
      China were discussed thoroughly.

PMID- 15859405
TI  - [Relationship between SO2 exposure mode and Chinese pine growth].
AB  - Chinese pine seedling, which age is 87 days, are exposed to SO2 in three
      treatments for 60 days from July 1, 2002 to August 29, 2002. In treatment 1 and
      treatment 2, the concentration of SO2 were 0.1 mg x m(-3) and 0.2 mg x m(-3),
      respectively. In treatment 3, the concentration of SO2 were 0.5 mg x m(-3) for 6
      hours and 0.1 mg x m(-3) for 18 hours per day. In treatment 1, the abnormity of
      stomata guard cell and leaf colour are not observed. There are no significant
      difference of chlorophyll content, carotenoid content of leaf, photosynthetic
      rate, transpiration rate, relative growth rate, and dry weight per plant compare
      with control, but the sulfur content of leaf increased 17% compare with control,
      the amount of potassium ion leaching from leaf increased 22% compare with
      control. In treatment 2, the abnormity of stomata guard cell and leaf colour are
      not observed. There are no significant difference of chlorophyll content,
      photosynthetic rate and transpiration rate compare with control. But compare with
      control, the carotenoid content of leaf decreased 5%, and the sulfur content of
      leaf increased 92%, the amount of potassium ion leaching from leaf increased 67%,
      dry weight decreased 4.5% per plant, the relative growth rate decreased 0.6 mg
      x(gxd)-1. In treatment 3, the abnormity of stomata guard cell and leaf colour are
      observed. The chlorophyll content were similar with control, but compare with
      control, the carotenoid content of leaf decreased 21%, and the sulfur content of
      leaf increased 104%, the amount of potassium ion leaching from leaf increased
      89%, photosynthetic rate decreased 5%, transpiration rate increased 8%, the dry
      weight decreased 7.6% per plant, the relative growth rate decreased 1.3mg x (gxd)
      1.

PMID- 15859406
TI  - [Evaluation of China' s regional sustainable utilization of water resources and
      its type classification].
AB  - Based on the idea of sustainable development, this paper analyzes the
      characteristics of sustainable utilization of water resources and builds the
      sustainable utilization evaluation system of water resources in the aspect of the
      status of water resources, the efficiency of water resources utilization, the
      stress of water resources sustainable utilization and the capacity of water
      resources sustainable utilization. According to this evaluation system, the
      sustainable utilization of water resources in China's 31 provincial regions is
      evaluated and is classified as 5 types correspondingly, namely high, relative
      high, medium, relative low and low types. The situation of water sustainable
      development presents the general decrease trend from the northeast coastal area
      to northwest inland. Compared with water resources endowment, the low water
      utilization efficiency is becoming another restrict to water sustainable
      utilization. There is obvious inverse correlation between water resources
      endowment and its utilization efficiency.

PMID- 15859407
TI  - [Nitrification and denitrification in the integrated vertical flow constructed
      wetlands].
AB  - Nitrification and denitrification in the different layers of the integrated
      vertical flow constructed wetlands (IVCW) are studied. The results show the
      constants rate of nitrification and denitrification in the strata of IVCW were
      0.01 - 6.35microg x (gxd)-1 and 3.37 - 4.19microg x (gxd)-1 respectively. The
      most probable number (MPN) method are employed to determine the number and
      distribution of nitrifying and denitrifying bacteria in the strata of the system.
      The results show that the numbers of nitrifying and denitrifying bacteria were
      7.5 x 10(3) - 1.1 x 10(5) MPN x g(-1) and 7.5 x 10(6) - 1.1 x 10 MPN x g(-1)
      respectively. The positive correlation between bacteria and their action was
      obvious (r = 0.9661, p < 0.001, r = 0.7722, p < 0.025). It is also observed that
      the number of nitrifying bacteria and nitrification rate was decreased along the
      direction of the water in the IVCW, while denitrifying bacteria and
      denitrification rate was increased. And there was the significant negative
      correlation between nitrification and denitrification rate(r = -0.9776, p <
      0.001).

PMID- 15859408
TI  - [Analysis on the removal efficiency of phosphorus in some substrates used in
      constructed wetland systems].
AB  - Constructed wetlands are widely used to purify wastewater in some developing
      countries. As filter substrates in such wetland, these substrates play important
      role on removal of pollutants from wastewater. Selecting suitable substrates is
      one of the effective ways to improve the performance of constructed wetland on
      treating wastewater. In this study the phosphorus adsorption capacities of sand,
      zeolite, vermiculite, two clay soils, two industrial by-products named steel slag
      and fly ash are examined for their potential use as substrate in constructed
      wetland. Both Freundlich and Langmuir adsorption isotherms are very fit for
      describing the adsorption characteristics of these substrates. Two industrial by
      products including steel slag and fly ash have higher phosphorus adsorption
      capacity, which had 50490 and 17934 mg x kg(-1) respectively. Followed
      vermiculite, two clay soils named yellow cinnamon and xiashu loess with
      phosphorus adsorption capacity of 3473, 1893.7 and 1582 mg x kg(-1) respectively.
      The zeolite and sand had the least phosphorus adsorption capacity with 813.7 and
      302 mg x kg(-1) respectively. The experiments on purifying phosphorus from
      synthesize domestic sewage using these substrates also demonstrate this
      conclusion. The ability of removal phosphorus of these substrates have closely
      relationship with their makeup and chemical properties such as pH, total calcium
      and reactive calcium, reactive Fe, Al including poorly coastal and amorphous Fe,
      Al oxide. The steel slag and fly ash with higher reactive Ca, such as calcium
      oxide, have better adsorption capacity of phosphorus than other substrates, and
      the substrates which contained more reactive Fe also have a better ability of
      adsorption phosphorus than others. To assess the environmental risk for using
      these substrates above, the phosphorus de-sorption characteristics of these
      substrates are also studied. The process of phosphorus desorption quickly reached
      equilibrium in no more than 4 hours in the experiments, the ratio of desorption
      and adsorption of phosphorus in substrates above is lower except sand. To take
      suitable measures to manage substrates above, the risk of pollution of phosphorus
      form these substrates will be controlled.

PMID- 15859409
TI  - [Evaluation of TTC and INT-electron transport system activity tests for heavy
      metal inhibition of activated sludge].
AB  - The effects of Cu2+, Zn2+, Cd2+, Hg2+, Ni2+, Pb2+ and Ag+ on TTC and INT-electron
      transport system activity are studied and the sensitivities of TTC and INT
      electron transport system activity to seven tested heavy metals are compared to
      evaluate both the parameters for assessing heavy metal inhibition of activated
      sludge. The median inhibitory concentration (IC50) of seven tested heavy metals
      measured via TTC-electron transport system activity is less than that measured
      via INT-electron transport system activity, which indicates that the INT-electron
      transport system activity is less sensitive to heavy metals than the TTC-electron
      transport system activity. The ranking of tested heavy metals in order of
      decreasing toxicity based on TTC-electron transport system activity was Hg2+,
      Cd2+, Cu2+, Ag+, Zn2+, Ni2+ and Pb2+ , and the ranking based on INT-electron
      transport system activity was Hg2+, Ag+, Cu2+, Cd2+, Zn2+, Ni2+ and Pb2+.

PMID- 15859410
TI  - [Stability of shortcut nitrification-denitrification].
AB  - The effects of temperature and aeration time on the stability of shortcut
      nitrification-denitrification are studied specially in some experiments are
      carried on a sequencing batch reactor (SBR) fed with soybean wastewater. Results
      show that shortcut nitrification-denitrification achieved by controlling
      temperature was not stable until the temperature was more than 28 degrees C. In
      addition, for the first time strong effect of excess aeration on shortcut
      nitrification-denitrification is observed. When the system run under excess
      aeration for twelve days, the type of nitrification turned from shortcut
      nitrification which nitrosation rate (NO2(-)-N/NOx(-) -N) was more than 96% to
      complete nitrification which nitrosation rate (NO2(-) -N/NOx(-) -N) was less than
      39.3%. So, in order to make shortcut nitrification-denitrification run stably,
      real-time process control must be used.

PMID- 15859411
TI  - [Enhancement of sewage sludge anaerobic digestibility by thermal hydrolysis
      pretreatment].
AB  - Biochemical methane potential (BMP) experiments of thermo-hydrolyzed sewage
      sludge are carried out to investigate the effects of thermal hydrolysis on the
      digestibility of sewage sludge. The results show that thermal hydrolysis
      pretreatment can facilitate the dissolving of organic solid in sludge, and
      soluble organics hydrolyzed into low molecular organics, in which volatile fat
      acids accounted for 30% - 40 % of soluble COD, so the digestibility of sewage
      sludge remarkably improved. The optimum pretreatment temperature and holding time
      were 170 degrees C and 30 minutes, under which the total COD removal rate
      enhanced from original 38.11% to 56.78%, and biogas production rate of COD in
      feeding sludge from 160mL/g to 250mL/g.

PMID- 15859412
TI  - [Effectiveness and mechanism of permanganate enhancing arsenite co-precipitation
      with ferric chloride].
AB  - The effectiveness and mechanism of permanganate enhancing arsenite (As(III)) co
      precipitation with ferric chloride is investigated. Effects of parameters such as
      pH, natural organic matter (NOM) on As removal are studied. Permanganate
      significantly enhances As(III) removal for ferric co-precipitation (FCP) process.
      With Fe(III) dosage increasing from 2mg/L to 8mg/L, As removal increased from
      41.3% to 75.4% for FCP process; for permanganate oxidation-ferric co
      precipitation (POFCP) process, however, corresponsive As removal increased from
      61.2% to 99.3% . As removal increased with higher pH for both processes;
      comparing to FCP process, pH had less effects on As removal for POFCP process;
      the presence of NOM reduced As removal for FCP process whereas no obvious
      reduction was observed for POFCP process. Permanganate oxidizing As(III) to As(V)
      is the main course for enhancing As(III ) removal; furthermore, products of
      permanganate reduction, hydrous MnO2 (s), also contribute to removing As. POFCP
      process exhibits good potential of removing As(III ) to assure chemical safety of
      drinking water.

PMID- 15859413
TI  - [Reducing sludge production by predation and its factors analysis in conventional
      activated sludge process].
AB  - Reducing excess sludge production induced by Oligochaete is carried out in a
      pilot scale of conventional activated sludge (CAS) reactor for 345 days. Worms
      occurred for nearly whole operating period except for the first 20 days, and
      continuously maintained at high density (over 30 total worms/mgVSS in aeration
      tank) for 172 days. Three types of worm were found, Aeolosoma hemprichicii and
      Nais elinguis alternatively dominated, but Pristina aequiseta occasionally
      presented. High worm density greatly contributes to both reducing sludge
      production and improving the sludge settling characteristics, and Nais elinguis
      had more potential for sludge reduction than Aeolosoma. Worm growth had impacts
      on effluent quality, and Nais elinguis growth affected effluent quality much more
      than Aeolosoma. Worm growth does not disturb the nitrification process, but PO4(3
      ) -P release into effluent occurres as Nais elinguis dominated. Analysis of
      factors affecting worm growth show that only SRT has no any impact on neither
      Aeolosoma nor Nais, however, both temperature and HRT can affect their growth
      very much.

PMID- 15859414
TI  - [Method of algae-bacterium biofilm to improve the water quality in eutrophic
      waters].
AB  - The quality of eutrophic waters was improved by the algae-bacterium biofilm,
      which covered over the artificial aquatic mat made from a kind of mend
      macromolecule material. Two series of experiments show that using the artificial
      aquatic mat technique, algae bloom was inhibited markedly. At the eleventh day,
      the transparency was increased from 6 cm to 62 cm; and the concentrations of
      COD(Mn), TP, TN and NH4(+) -N were decreased to 92.89%, 49.25% , 94.97% and
      70.15% respectively. The DO concentration also kept in certain satisfied level
      for using the algae-bacterium biofilm method. The suitable and economical density
      was about 8 - 16 bunchs/m(2) when the ratio of the artificial aquatic mat length
      to water depth was 0.7.

PMID- 15859415
TI  - [Effect of coagulation on preventing membrane from fouling].
AB  - In this experiment, the effects on improve of flux and prevention of membrane
      from fouling is studied. The results demonstrate that after backwashing, the flux
      was completely recovered by addition of 4mg/L and l0mg/L(as Al), while the flux
      was only 40% of initial flux without coagulation pretreatment. It is also
      observed that whether or not prevention of fouling by coagulation are depended on
      the characteristics of cake layer formed on membrane surface during membrane
      filtration. In the presence of filtration of coagulation floc suspension,
      coagulation can form cake layer on membrane surface, thus prevent membrane from
      fouling effectively, while in the presence of filtration of supernatant, fouling
      are occurred due to cake layer comprising small, neutral, hydrophilic compounds,
      which can not remove by backwash.

PMID- 15859416
TI  - [Spatial and temporal variation of the natural reproducible ability of water
      resource in the northeast part of China and its response to the land use change].
AB  - With respect to the water cycling, the natural reproducible ability of water
      resource (NRAWR) was expressed, and the spatial and temporal differences of NRAWR
      in the northeast part of China were anatomized systematically with the GIS
      techniques. Furthermore, the response of NRAWR in the northeast part of China to
      land use changes was described based on land use patterns of the northeast part
      of China in 1986,1996 and 2000. Water resource in the northeast part of China has
      the distinct spatial and temporal variation during the period from 1956 to 2001
      with the multi-year volume of 199.152 billion m(3), and the temporal change of
      NRAWR has 33-year, 11-year and 4-year cycles. In the phase from 1980 to 2001, the
      NRAWR in the northeast part of China has the descending trend, and the yearly
      variation range and intensity have marked spatial evolutional features. The
      coupling change of NRAWR and land use change shows that, in order to maintaining
      an higher NRAWR level under the condition of the acute anthropic interferes in
      the northeast part of China, the land use pattern should be adjusted based on the
      distributed eco-hydrological mechanism.

PMID- 15859417
TI  - [Assessing the ecological risk of effluents from different advanced treatment
      units by using a battery of bioassay].
AB  - In this paper, effluents from different advanced treatment units, which were
      reclaimed for Olympic Park, were assessed regarding to the removal efficiencies
      of the technologies on acute toxicants, Ah-acceptor chemicals and estrogenic
      substances by using a battery of bioassays. The results showed that advanced
      treatments using ultra-filtration and activated carbon absorption were suitable
      for removal of toxic organic substances from STP effluent. Activated carbon
      absorption was the most effective technology to remove acute toxicants and Ah
      acceptor chemicals, and the removal efficiency of Ah-acceptor chemicals reached
      98%. Ultra-filtration was suitable for removing nonpolar acute toxicants and
      polar estrogenic chemicals. Nonpolar fraction extracted from water after ultra
      filtration treatment showed 100% percentage survival of cell in the acute toxic
      assay. E2-TEQ was reduced from 0.13 pmol x L(-1) to 0.04 pmol x L(-1) in the
      polar fraction extracted from water after ultra-filtration. Treatments with micro
      filtration and osmosis did not manifest sufficient efficiencies for removal of
      toxic organic substances. In complex matrix, interactions may occur among
      different toxic components to interfere the bioassay results. Therefore
      fractionation of organic concentrate before bioassay is necessary.

PMID- 15859418
TI  - [Characteristics and chlorination activity of natural organic matter in water].
AB  - XAD resin adsorption technique is used to separate natural organic matter in the
      water into four fractions, namely: humic acid fraction, fulvic acid fraction,
      hydrophilic acid fraction and hydrophilic non acid fraction. Trihalomethane
      formation velocity and chlorination activity of each fraction are studied.
      Results show that fulvic acid is the main components which contained 50.7% of
      total organic carbon and produce more trihalomethane than other fractions in the
      raw water. Humic acid, fulvic acid and hydrophilic acid exhibited more
      chlorination activity and faster reactive velocity with chlorine than hydrophilic
      non acid fraction.

PMID- 15859419
TI  - [Effects of PEG additives on structure and performance of blend membranes].
AB  - Polysulfone(PSf) /polymer A blend membranes are fabricated by phase inversion
      process from casting solution of PSf, polymer A, DMAc, and polyethylene glycol
      (PEG). The resulting membranes prepared by changing the molecular weight of PEG
      additives are characterized by scanning electron microscope observation,
      measurement of water flux and trypsin retention. Experiments of water flux show
      that water fluxes have non-liner relationship with PEG molecular weight. The
      water flux of the membrane prepared from the PSf/A/PEG-4000/DMAc casting solution
      was 115.2mL x (cm2 x h)-1, six time as much as membrane without PEG-0. The PEG as
      a non-solvent changed thermodynamic properties in polymer solution, promoting
      phase demixing of casting solution; otherwise, it increased solution viscosity,
      delaying phase demixing. The two different effects work simultaneously,
      influencing structure and performance of the membranes.

PMID- 15859420
TI  - [Radiation transformation mechanism in a photocatalytic reactor of three-phase
      internal circulating fluidized bed].
AB  - A novel three-phase internal circulating fluidized bed photocatalytic reactor was
      established and the radiation transformation in which was investigated. The
      experimental results indicate that with the interaction of gas and solid (gas
      flux > 0.3m3/h), the radiation transformation in the reactor along radial
      direction conforms to a definite exponential function, which agrees to formula
      Rose about the rules of light intensity distribution through evenly suspended
      particles. The value of radiation energy is affected by the initial light
      intensity, the concentration of photocatalyst and the thickness of liquid layer.
      The aerated gas amount only influence the state of the fluidized bed and has
      little effect on the distribution of light intensity along radical direction.
      Photocatalytic degradation of Rhodamine B indicate that the efficiency of three
      phase internal circulating fluidized bed is much higher than slurry bed. The
      optimal catalyst concentration of this system is 10 - 12g/L.

PMID- 15859421
TI  - [Electrochemical reduction of nitrobenzene under mild conditions].
AB  - Effect of cathode materials (S1, S2, AB5, graphite, Ni plate, Fe plate) on the
      electrochemical reduction of nitrobenzene of light concentration under mild
      conditions(current density less than 1.0 mA/cm2, pH in the range of 4 - 9), was
      experimentally studied. In aqueous solution, S1, S2 and AB5 electrodes showed
      high selectivity of nitrobenzene reduction to aniline, with the nitrobenzene
      conversion and aniline yield being over 85% and 75%, respectively. The results
      obtained by cyclic voltammograms and single sweep voltammograms showed that
      nitrobenzene was directly reduced at S1 and S2 electrodes, while reduced by
      hydrogen at AB5 electrode. The products electroreduced from nitrobenzene on S1,
      S2 and AB5 cathodes could be easily degraded by aniline degrading strain AN3
      under aerobic condition.

PMID- 15859422
TI  - [Effect of surfactant on the evaporation of BTEX from static water].
AB  - Effect of surfactant on the evaporative loss of benzene, toluene and ethylbenzene
      from static water was researched and the mechanism of surfactant was studied, so
      as try to supply theoretical reference for the effect of surfactant on the
      evaporation of complex pollution in water system. Sodium dodecylbenzene sulfonate
      (SDBS), cetyltrimethyl ammonium bromide (CTMAB) and polyoxyethylene(4) lauryl
      ether(Brij30) were used in the experiment. The results show when the surfactant
      concentrations exceeded their critical micelle concentrations (CMCs) and were set
      above 1 000mg/L, 2 000mg/L and 3 000mg/L respectively, the evaporative loss
      velocity of ethylbenzene, toluene and benzene began to decrease and their half
      lives prolonged consequently. The main reason for the decrease of the evaporative
      loss velocity of BTEX was surfactant micelles formed and it caused the ratio of
      the concentration of BTEX at the liquid surface to that at the bulk liquid phase
      to diminish. Comparing CTMAB and Brij30 with SDBS, the evaporative loss of BTEX
      from static water decreased more evidently in CTMAB and Brij30 solutions. The
      positive relation was found between the restraining ability of a surfactant and
      the octanol-water partition coefficients or Henry's law constants of BTEX.

PMID- 15859423
TI  - [Terramycin wastewater treatment with combination hydrolysis-denitrification
      nitrification].
AB  - Successive hydrolysis-denitrification-nitrification process is adopted to treat
      terramycin wastewater in lab scale for 70 days. Two sludge bed reactors are used
      respectively for hydrolysis and denitrification, and two biofilm reactors are
      used for nitrification. When the COD and NH4+ -N concentrations in influent were
      2 200 - 3 000mg/L and 400 - 460mg/L, more than 80% COD and TN removals were
      achieved under a total HRT of 56h. The COD of the effluent was reduced to 293mg/L
      through coagulation under a polyferric sulfate dose of 48mg/L as Fe.

PMID- 15859424
TI  - [Evaluation of eco-toxicity of integral quality of soils].
AB  - Soil samples are collected from several sites along the wastewater irrigation
      channel, western Shenyang. The concentration of heavy metal(Cd)and mineral oil is
      analyzed. The eco-toxicity of soil is evaluated. Heavy metal (Cd) isdetermined by
      atom adsorption spectrometer(AAS), mineral oil is measured by UV spectrometer.
      The eco-toxicity of soil is based on the method of international standardization
      of organization (ISO) and OECD guideline with some modification. With inhibition
      rates of root elongation of wheat as endpoint seed germination test was performed
      and the duration period was 50h. With lethal and sub-lethal effects as endpoint
      earthworms test was conducted and the experimental period was 28d. And
      micronuclear( MCN) test was conducted. Results show the mineral oil in soils were
      145 mg/kg - 1 121mg/kg, Cd was 0.34mg/kg - 1.81mg/kg. The inhibition rate of root
      elongation based on germination test was 2.0% - 35.1%, MCN in soil was
      significant higher than that in the control. The mortality rates of earworms were
      0% - 40%. The inhibition rates of body weight growth were -2.3 % to -19.4% from
      14d to -2.1% - 10.7% in 28d. The maximum value of MCN in soils was 6.62/100. The
      study indicates a lower accumulation of pollutants in soils but enhanced
      ecotoxicity.

PMID- 15859425
TI  - [Acid mining drainage impacts on the separation between iron and manganese in
      sediments of the Aha Lake, Guizhou Province].
AB  - Since the Aha Lake, located in Guizhou Province, China, was enlarged in 1982, a
      great amount of iron and manganese were input into it owing to the uninterrupted
      pollution from acidic mining drainage of coal mines (AMD). The results show that
      dissolved Fe2+ and Mn2+, mainly from AMD, were markedly separated each other as
      water flowed from inlet to downstream. The Aha lake water, with the average pH
      equal to 7.28, was not acidified just because the lake is developed in the karst
      area and people continuously put lime in it in recent years. Fe2 + and Mn2 +
      deposit in the different locations in lake because of the difference of oxidizing
      rate between Fe2+ and Mn2+ during water flowing from inlet to downstream, and
      also forming the horizontal separation along the lake water flowing direction.
      Manganese tends to be obviously enriched in the upper of sediment in lake's deep
      locations, presenting the remarkable separation with iron in the vertical
      section. After normalized by Ti content in sediment, it is obvious that the
      remarkable separation between iron and manganese corresponds with the enlargement
      of lake in 1982. As shown in the concentration profile of pore water in sediment,
      iron was remobilized weakly while manganese reduction mainly happens in the upper
      of sediment, indicating its strong remobilization. Based on the studies, a
      mechanism for environment and fractionation of Fe2+ /Mn2 + during water flowing
      in the lake was also demonstrated.

PMID- 15859426
TI  - [Multi-scale spatial relations of PAHs and soil properties in Tianjin area].
AB  - Polycyclic aromatic hydrocarbons(PAHs) in soil have serious latent danger to our
      human health. Based on the sampling data, the spatial scale-dependent
      correlations of PAHs content and some soil properties are analyzed by Factorial
      Kriging for top soil in Tianjin area. Based on 1 88 topsoil samples in Tianjin
      area, pH, TOC, CLAY and sum of 16prior PAHs are tested. Resultsshow that
      significant difference on spatial correlations at different spatial scales
      between the PAHs content and soil properties such as pH, TOC and CLAY existed in
      the studies area.

PMID- 15859427
TI  - [Ion beam implantation in breeding efficient degradation bacteria].
AB  - Sphingomonas sp. AN1 was mutagenized and breeded by N+ implantation, mutants
      capable of degrading anthrancene was obtained. The research review that the
      degrading rate increased by 29.3% and 36.2% while the mutagenized rate was 80% -
      100% and 60% - 80%. In addition, the maximum concentration of enduring anthracene
      reached 300mg/L and 400mg/L. Their heritance stability were examined for fifteen
      transfers. Among these strains, two strains,AN815-3 and AN315-5S,showed
      predominant character of survival ability and degrading activity. Their rate of
      degrading anthrancene reached 73% and 75% respectively. Effect of positive
      mutagenesis is evident.

PMID- 15859428
TI  - [Isolation and characterization of a p-chloroaniline-degrading bacterial strain].
AB  - A bacterial strain that degrades p-chloroaniline is isolated from activated
      sludge of wastewater treatment plant treating wastewater from a chemical factory.
      Results indicate that this strain took p-chloroaniline as sole carbon, nitrogen
      and energy sources. It is identified as Diaphorobacter sp. PCA039 according to
      its morphology, and biochemical properties, and 16S rDNA sequence analysis.
      Further study indicate that chloride anion is released simultaneously and
      stoichemically to p-chloroaniline degradation during cultivation. The optimal pH
      and temperature for cell growth and p-chloroaniline degradation were 7.5 and 30
      degrees C, respectively, and the optimal concentration of p-chloroaniline in
      three days was 300 mg/L (2.35 mmol/L). Enzymatic analysis show that initial
      reactions of p-chloroaniline degradation by Diaphorobacter sp. PCA039 are
      catalyzed by aniline dioxygenase and chlorocatechol 2,3-dioxygenase.

PMID- 15859429
TI  - [Screening for phenanthrene-degrading bacteria and its characteristics].
AB  - One bacterial strain, designated as Phx1, was isolated from Daqing oil-field with
      the method of sublimate-plate and determination of dioxygenase activity. Phxl can
      degrade phenanthrene (100microg/mL, in LB media) completely in 24 h. Compared to
      MSM, LB and broth media can accelerate the phenanthrene degradation, promote the
      degradation of intermediates especially. With the method of plasmid elimination,
      it was proved that the genes encoding for degradation of phenanthrene locate on
      the larger one of the two plasmids. According to morphological and physio
      biochemical characteristics, Phxl was identified as Agrobacterium sp. and was
      probably a new species of the genus Agrobacterium due to its 16S rDNA sequence
      which has the similarities of 97.8 % and 96.6% to Agrobacterium tumefaciens UP-3
      and Agrobacterium albertimagni respectively.

PMID- 15859430
TI  - [Population exposure to HCH in Tianjin area].
AB  - The population exposure to HCH in Tianjin area is estimated based on field data
      on media concentration and other data from the literature. A multimedia
      /multipathway human exposure model is employed to calculate the population' s
      Chronic Daily Intake (CDI) of HCH. The population's lifetime CDI was 0.05microg x
      (kg x d)-1, and the daily exposures of child, youth and adult were 0.10, 0.06,
      and 0.04microg x (kg x d)-1, respectively. The result indicates that diet
      exposure was the most important route, accounting for 87% of total dose.
      Respiration ranked second and contributed 5% - 10% of the total dose.

PMID- 15859431
TI  - [Loss of life expectancy analysis for cancer risk in Tianjin area].
AB  - Loss of Life Expectancy was proposed as the single metric for health risk
      assessment. Based on the statistical data of population in Tianjin, it was
      calculated that the unit cancer risk (10(-5)) equivalents to 58.47 and 66.82
      minutes of life expectancy loss for male and female, respectively. The results
      depend strongly on the background rate of cancer, with little response for
      associated parameters.

PMID- 15859432
TI  - [Effects of long-term exposure of low level zinc and zn-EDTA complex on zinc
      accumulation and antioxidant defense system in liver of Carassius auratus].
AB  - The effects of low level zinc(Zn2+)and its EDTA complex on zinc accumulation and
      antioxidant enzymes,such as catalase (CAT), superoxide dismutase (SOD),
      glutathione S-transferase (GST), glutathione peroxidase (GPx) in the liver of
      Carassius auratus are studied after 40 day exposure. The results show that zinc
      accumulation is significantly increased with higher zinc concentration. When fish
      are exposed to Zn-EDTA, the zinc accumulation in the liver of fish increased
      slightly according to the control. SOD, GST, CAT and GPx activity all decrease
      with adding to Zn2+ and Zn-EDTA in waters. However, the decrease of CAT and GPx
      activities of fish liver are alleviated with the addition of EDTA. The GST
      activities increased at lower concentration solutions ( < 0.05mg-L(-1) ), however
      its activities were inhibited at higher Zn2 + solution ( > 0.05mgL- ). These
      results suggest that CAT and GPx are more sensitive to low zinc exposure than SOD
      and GST, and they can be served as biomarkers of low concentration zinc exposure
      in aquatic ecosystem.

PMID- 15859433
TI  - [Expression of c-FOS protein in rat hippocampus by inducing of mercury
      contaminated rice].
AB  - In order to probe into the biological effects of mercury in typical mercury
      contaminated area and try to apply the expression of immediately early gene c-fos
      in brain to early predict the neurotoxicity of mercury in typical polluted areas,
      the expression of c-FOS protein in rat hippocampus is observed using
      immunocytochemical methods. The results show the mercury pollutes rice induced
      significantly the expression of c-FOS protein in hippccampus;the antagonisis
      between selenium and mercury on the exposure process. It is suggested that c-fos
      can be used as an effective index of detecting and assessing neurotoxicology of
      mercury polluted areas.

PMID- 15859434
TI  - [Effect of acid rain on seed germination of rice, wheat and rape].
AB  - Rice, wheat and rape seeds were treated with simulated acid rain at pH 2.0, 2.5,
      3.0, 3.5, 4.0 and 5.0 levels for 7 days in order to understand the effects of
      acid rain on seed germination of various acid-fast plant. The germination test
      showed that seed germination was absolutely inhibited at pH 2.0 for three
      species. Rice and wheat seeds germinated abnormally at pH 2.5. WhenpH values
      above 3.0, percentage germination, germination energy, germination index, vigor
      index of rice, wheat and rape seeds increased in relation with decreased acidity
      levels. In contrast, the percentage of abnormal germination of rice and wheat
      decreased. The experiment data about physiological aspect demonstrated that water
      absorption rate, respiratory rate and storage reserve transformation rate of
      rice, wheat and rape seeds also increased with increased pH values. The storage
      loss of rice and wheat increased with increased pH values but that of rape
      decreased. Inhibition index of shoot and root length of three kinds of seeds
      decreased in relation with increased pH values. The amplitude difference of index
      of rice was lower than that of wheat, and wheat was lower than that of rape. The
      experiment data showed that rice had stronger fastness than wheat and rape, wheat
      had stronger fastness than rape under acid rain stress.

PMID- 15859435
TI  - [Joint acute toxicity of fipronil and bata-cypermethrin to protozoa community].
AB  - Compared with the toxicity test on single organism, the effects of toxic
      pollutants on organisms at community level are more reliable. The acute single
      and joint toxic effects of Fipronil and Bata-cypermethrin on freshwater protozoa
      community are studied in this paper. The results show that the 48h-LC50 of
      Fipronil and Bata-cypermethrin to the microbial community was 35.83mg x L(- 1),
      1.92mg x L(-1), the joint toxicity of Bata-cypermethrin and Fipronil was
      antagonism in 48h with toxicity 1: 1 to freshwater protozoa community, and
      Additive Index was -0.08. The structure of protozoa community would change in a
      low concentration of Bata-cypermethrin and Fipronil mixture; the species and
      population of Algivores(A) and Predators Raptors (P) would reduce but
      Bactivoresdetrivores(B) would become predominant relatively.

PMID- 15859436
TI  - [Influence of different sorbents on adsorption effect of ammonia and compost
      property in aerobic composting].
AB  - The three kinds of sorbents of 0.18% KH2PO4, 0.06% KH2PO4 + 15% sawdust mixture
      and 30% sawdust are added separately into composting to investigate their
      adsorption effect on ammonia. The experiment results exhibite that all the
      sorbents can restrain ammonia volatilizing. But sorption of 0.18% KH2PO4 sorbnet
      was best of all, one of 0.06% KH2PO4 + 15% sawdust mixture sorbent was secondly,
      one of 30% sawdust sorbent was thirdly. The total nitrogen loss ratios were
      separately reduced 25%, 23% and 17% after adding the three kinds of sorbents into
      composting. However, excessive KH2PO4 would produce negative influence on compost
      property, such as pH value being lessened, microorganism activity being reduced,
      and finally resulting in the reduction of biodegradation ratio of organic matter
      also. Comparing with it, there were not these problems as 0.06% KH2PO4 + 15%
      sawdust mixture being sorbent. The mixture sorbent not only produced finer
      adsorption effect on ammonia, but also made biodegradation ratio of organic
      matter to be promoted 7%.

PMID- 15859437
TI  - [Environmental effects of mercury around a large scale MSW incineration plant].
AB  - Samples of soil, vegetables, crops and air collected from Yuqiao Incineration
      Paint, Pudong Shanghai, were analyzed with an AMA-254 liquid/solid mercury
      analyzer. It is shown that background levels(BLs,2001) of mercury in surface soil
      is a little higher, mercury content in soils one year after operation(2002) and
      two year(2003) were both higher than BLs. The levels of mercury in vegetables is
      higher than Standard levels (GB 2762-94), the content of mercury in Soya and
      broomcorn sampled in 2003 was 2.3 and 2.7 times than that in 2002. Atmospheric
      mercury levels were 10.1, 5.0 and 10.6 ng/m3 in up-site,site and down-site.

PMID- 15859438
TI  - [Setup of high voltage direct circuit equivalent circuit model in leakage
      detection of landfill].
AB  - An equivalent circuit model is put forward through analysis of the experiment
      data under the conditions of applying 400V, 350V and 300V DC supply power to a
      small-scale simulated landfill. Due to the fact that the existence of the HDPE
      geomembrane liner endows the model with commutating character, the electrolytic
      capacity increases as the area of geomembrane liner and the supplying electric
      voltage increase. The contact electric resistance of the power supply electrode
      is in direct proportion to earth electric resistance rate, and in relation to the
      diameter of the electrode and the depth of the earth. Moreover, the contact
      resistance is mainly determined by the earth electric resistance around the
      electrode (the influence induced by the earth farther than 10 times electrode
      radius is less than 10 percent of those involved by all resistance), hence
      decrease of the earth electric resistance rate around the electrode may result in
      effective decrease of the contact electric resistance of the electrode.

PMID- 15859439
TI  - [Calculation method of absolute quantum yields in photocatalytic slurry reactor
      based on cylindrical light].
AB  - Heterogeneous photocatalysis in slurry reactors have the particular
      characteristic that the catalyst particles not only absorb but also scatter
      photons so the radiation scattering can not be neglected. However, it is very
      difficult in mathematics to obtain the rigorous solution of the radiative
      transfer equation. Consequently present methods, in which the apparent quantum
      yields can be calculated by employing the incident radiation intensity, always
      underestimate quantum yields calculations. In this paper, a method is developed
      to produce absolute values of photocatalytic quantum yields in slurry reactor
      based on cylindrical UV light source. In a typical laboratory reactor (diameter
      equal to 5.6 cm and length equal to 10 cm) the values for the photocatalytic
      degradation of phenol are reported under precisely defined conditions. The true
      value of the local volumetric rate of photon absorption (LVRPA) can be obtained.
      It was shown that apparent quantum yields differ from true quantum yields 7.08%
      and that for the same geometric arrangement, vanishing fraction accounts for 1.1%
      of the incident radiation. The method can be used to compare reactivity of
      different catalysts or, for a given catalyst, reactivity with different model
      compounds and as a principle to design a reactor.

PMID- 15859440
TI  - The current status of living donor liver transplantation.
AB  - In response to the critical organ shortage, transplant professionals have
      utilized living donors in an attempt to decrease the mortality rate associated
      with waiting on the liver transplant list. Although the surgical techniques were
      first utilized clinically 15 years ago, application of LDLT has been somewhat
      limited by the steep learning curve associated with developing a program.
      Clinical success with LDLT in children was realized early in the experience and
      application of the techniques to the adult population has occurred more recently.
      Although transplant centers embark on LDLT with enthusiasm, the safety of the
      donor must always be at the forefront of the process. Potential donors must come
      to the decision to donate without pressure from members of the family or
      transplant team. He/she should also be assigned advocates who constantly promote
      the donor's best interest. Failure to adhere to strict donor evaluation protocols
      and standardized operative techniques could result in disastrous consequences.

PMID- 15859441
TI  - Robert S. Locke--a Canadian dental anaesthesia pioneer.

PMID- 15859442
TI  - Need and demand for sedation or general anesthesia in dentistry: a national
      survey of the Canadian population.
AB  - The aim of this study was to assess the need and demand for sedation or general
      anesthesia (GA) for dentistry in the Canadian adult population. A national
      telephone survey of 1101 Canadians found that 9.8% were somewhat afraid of dental
      treatment, with another 5.5% having a high level of fear. Fear or anxiety was the
      reason why 7.6% had ever missed, cancelled, or avoided a dental appointment. Of
      those with high fear, 49.2% had avoided a dental appointment at some point
      because of fear or anxiety as opposed to only 5.2% from the no or low fear group.
      Regarding demand, 12.4% were definitely interested in sedation or GA for their
      dentistry and 42.3% were interested depending on cost. Of those with high fear,
      31.1% were definitely interested, with 54.1% interested depending on cost. In a
      hypothetical situation where endodontics was required because of a severe
      toothache, 12.7% reported high fear. This decreased to 5.4% if sedation or GA
      were available. For this procedure, 20.4% were definitely interested in sedation
      or GA, and another 46.1% were interested depending on cost. The prevalence of,
      and preference for, sedation or GA was assessed for specific dental procedures.
      The proportion of the population with a preference for sedation or GA was 7.2%
      for cleaning, 18% for fillings or crowns, 54.7% for endodontics, 68.2% for
      periodontal surgery, and 46.5% for extraction. For each procedure, the proportion
      expressing a preference for sedation or GA was significantly greater than the
      proportion having received treatment with sedation or GA (P < 0.001). In
      conclusion, this study demonstrates that there is significant need and demand for
      sedation and GA in the Canadian adult population.

PMID- 15859443
TI  - Continuous infusion propofol general anesthesia for dental treatment in patients
      with progressive muscular dystrophy.
AB  - Progressive muscular dystrophy may produce abnormal reactions to several drugs.
      There is no consensus of opinion regarding the continuous infusion of propofol in
      patients with progressive muscular dystrophy. We successfully treated 2 patients
      with progressive muscular dystrophy who were anesthetized with a continuous
      infusion of propofol. In case 1, a 19-year-old, 59-kg man with Becker muscular
      dystrophy and mental retardation was scheduled for dental treatment under general
      anesthesia. General anesthesia was maintained by a continuous infusion of 6-10
      mg/kg propofol per hour and an inhalational mixture of 67% nitrous oxide and 33%
      oxygen. No complications were observed during or after the operation. In case 2,
      a 5-year-old, 11-kg boy with Fukuyama type congenital muscular dystrophy and
      slight mental retardation was scheduled for dental treatment under general
      anesthesia. General anesthesia was maintained with a continuous infusion of 6-12
      mg/kg propofol per hour and an inhalational mixture of 0.5-1.5% sevoflurane in
      67% nitrous oxide and 33% oxygen. No complications were observed during or after
      the operation. It is speculated that a continuous infusion of propofol in
      progressive muscular dystrophy does not cause malignant hyperthermia because
      serum levels of creatine phosphokinase and myoglobin decreased after our
      anesthetic management. Furthermore, our observations suggest that sevoflurane may
      have some advantages in patients with progressive type muscular dystrophies other
      than Duchenne muscular dystrophy and Becker muscular dystrophy. In conclusion,
      our cases suggest that a continuous infusion of propofol for the patients with
      progressive muscular dystrophy is a safe component of our anesthetic strategy.

PMID- 15859444
TI  - Hallucinations and delirium in the dental office following triazolam
      administration.
AB  - A rare and unusual case of hallucinations following triazolam administration is
      reported. A review of the literature suggests that hallucinations following
      triazolam are rare; this is the first report of such a reaction when triazolam
      was used for oral conscious sedation in dentistry. A discussion of dental
      implications follows with emphasis on complete medical history evaluation before
      administering oral sedatives. We conclude that the proper selection of oral
      sedation candidates, coupled with recognition and management of adverse events,
      is essential.

PMID- 15859445
TI  - Postoperative hyperthermia of unknown origin treated with dantrolene sodium.
AB  - An 11-year-old girl was scheduled for alveolar cleft bone grafting with an iliac
      bone under general anesthesia. Anesthesia was performed with 70% nitrous oxide,
      30% oxygen, and propofol. On the first and second postoperative day, persistent
      hyperthermia was observed. Because the administration of diclofenac sodium had
      not been effective for the hyperthermia, dantrolene sodium was given. Her body
      temperature gradually dropped and returned to normal level on the fifth
      postoperative day. The hyperthermia in the present case might have been caused by
      a rapidly elevated muscle metabolism in response to pain and stress after the
      propofol anesthesia. The oral administration of dantrolene sodium successfully
      lowered the patient's high body temperature.

PMID- 15859446
TI  - A case report of malignant hyperthermia in a dental clinic operating room.
AB  - A healthy 5-year-old boy presented for arch bar placement under general
      anesthesia in an operating room in a dental school. The patient had previously
      undergone general anesthesia without complication, and no family history of
      anesthetic problems were reported. Halothane mask induction, intravenous catheter
      placement, and nasal intubation proceeded uneventfully without the aid of a
      muscle relaxant. Halfway through the procedure, signs and symptoms of malignant
      hyperthermia, including muscle rigidity, hypercarbia, tachypnea, and tachycardia
      were noted. Immediate treatment, including discontinuation of the triggering
      agent, dantrolene administration, and cooling measures were applied, and once
      stable, the child was transferred to Columbus Children's Hospital for further
      management. The patient experienced no postoperative complications. Further
      discussion regarding the pathophysiology and management of malignant hyperthermia
      is provided.

PMID- 15859447
TI  - Preemptive analgesia and local anesthesia as a supplement to general anesthesia:
      a review.
AB  - General anesthesia (GA) and local anesthesia (LA) evolved on separate tracks.
      Procedures that could not be performed under LA were typically conducted under
      GA. Decoding of afferent linkage of peripheral noxious stimuli has provided
      important understanding that may change the way we traditionally treat surgical
      pain. In the 1980s, animal studies suggested that preemptive peripheral blocking
      of painful (nociceptive) stimuli to the central nervous system with regional
      anesthesia or LA and nonsteroidal analgesics could be beneficial in attenuating
      postoperative pain. Clinical studies based on this knowledge suggest combining LA
      with GA, and perhaps non-steroidal analgesics with or without narcotics, to
      reduce the severity of postoperative pain. General anesthetics can be given in
      lower minimal alveolar concentration when combined with LA, and recovery
      characteristics are superior. Increasing evidence suggests that the combined use
      of GA and LA may reduce the afferent barrage of surgery, and that preemptive
      analgesia may reduce postoperative pain and should be used in patient care. This
      article reviews the evidence supporting the combined use of LA or analgesics with
      GA or sedation to provide improved pain management after surgery.

PMID- 15859448
TI  - [The frame of non-canonical theory of heredity: from genes to epigenes].
AB  - Particular theory of heredity that exceeds the limits of mendelian genetics is
      suggested. The model based on five sufficiently obvious assumptions (accepted as
      axioms) As consequence of these axioms the strict statements concerningfunctional
      heredity memory were formulated in mathematical terms. Molecular-genetic
      realization of the memory cells appears as new class of heredity units--epigenes.
      In the epigenes part f hereditary information is contained, encoded and
      transmitted beyond the primary structure of DNA molecules of genome. Epigenes
      capable to conserve sequences of genes functional states in the course of
      ontogenesis and provide transmission of information contained in this states
      throw consequent generations. It was shown that epigenes differ from genes at
      least by encoding method of heredity information. There are three functional
      equivalent classes of really existing epigenes mechanisms: dynamic,
      modificational and transpositional; and there is one hypothetical class-
      invertional. It was shown that a lot of experimental data concerning epigenetic
      mechanism of heredity is in accord with theoretical conclusions concerning
      epigenes existence. Moreover, we constructed an artificial epigenes by genetic
      engineering methods. The existence of epigenes means that obtaining complete
      genome sequence, its physical and genetic maps, as well as distinguishing the
      rules of genes function encoding by its primary structure do not provide complete
      decoding of hereditary information. The role of epigenes in ontogenesis and
      phylogenesis was examined. It was shown that even elementary epigenetic systems
      could determine key ontogenesis events. Epigenetic system could serve as the
      basis of non-darwinian evolutionary strategies by means of "memorization of
      rather unsuccessfully steps of evolution" and conservation of alternative
      variants of ontogenesis. Teleonomic hypothesis on functional heredity memory was
      formulated. This theory provides explanation of phenomena of acquired features
      inheritance and molecular mechanisms of stress-induced evolution.

PMID- 15859449
TI  - [The latitude-zonal and spatial-successional trends in the distribution of
      yeasts].
AB  - The distribution of yeasts in natural habitats is analyzed in the different
      nature zones of the former USSR (from tundra to desert) using the results of long
      term research. Yeast community structure is changing in parallel to different
      stages of plant debris decay as well as to latitude-zonal gradient. These changes
      are not fluctuating but trend ones. As mineralization of plant debris proceeds
      the availability of sugars decreases and habitat become more extremal for yeasts
      which are typical saccharolytics. It causes decrease in species abundance and
      species diversity. At the same time in zonal gradient the most significant
      changes take place in the relative abundance of dominant species, genera or
      higher taxonomic groups. The thermotolerant species occurred more often in the
      southern regions while psychrophilic species dominate in the north. Soil yeast
      communities become more polytrophic in the north latitudes where mineralization
      of organic matter is rather low. Species inhabiting climatic pessimum areas
      usually form chlamidospores.

PMID- 15859450
TI  - [Successions in the forest-steppe under climate changes: a modelling approach].
AB  - The paper represents an attempt to apply the general principles of modelling
      vegetation dynamics under climate changes to a study of the long-term vegetation
      dynamics in the forest-steppe zone of the European territory of Russia, with a
      purpose to forecast under special climatic scenarios. An original technique is
      used to construct a Markov chain as a model of vegetation succession. The
      technique emanated from gebotanic knowledge generalized as a scheme of
      successional transitions with estimates of the average duration for certain
      stages of succession. Whenever the knowledge related the stage duration to
      certain (climate-sensitive) factors of the environment, the fundamental
      potentiality arises to model the temporal course of succession as a function of a
      given scenario for how the key factors change. In the formal terms, the model
      represents a random chain of the Markov kind with a finite number of states and
      discrete time of transitions by the given scheme. Relative square distributions
      of succession stages under concern at any time moment (within an adopted
      scenario) appear as the model outcome (forecasts), as well as estimates of the
      attainment time for certain states of the vegetation in the territory under
      study. A method is proposed to describe dynamics of the phytomass production and
      stores (and the corresponding model trajectories are obtained) for a given
      scenario.

PMID- 15859451
TI  - ["Phylogenetic presumptions"--can jurisprudence terms promote comparative
      biology?].
AB  - The paper presents the results of a critical analysis of the "phylogenetic
      presumptions" conception by means of its comparison with the hypothetic-deductive
      method of the phylogeny reconstruction within the framework of the evolutionary
      systematics. Rasnitsyn (1988, 2002) suggested this conception by analogy with the
      presumption of innocence in jurisprudence, where it has only moral grounds.
      Premises of all twelve the "phylogenetic presumptions" are known for a long time
      as the criteria of character homology and polarity or as the criteria of
      relationship between organisms. Many of them are inductive generalizations based
      on a large body of data and therefore are currently accepted by most of
      taxonomists as criteria or corresponding rules, but not as presumptions with the
      imperative "it is true until the contrary is proved". The application of the
      juristic term "presumption" in phylogenetics introduces neither methodical
      profits, nor anything to gain a better insight of problems of the phylogenetic
      reconstruction. Moreover, it gives ill effects as, by analogy with a judicially
      charged person and his legal defense, it allows a researcher not to prove or
      substantiate his statements on characters and relationships. Some of Rasnitsyn's
      presumptions correspond to criteria, which have been recognized as invalid ones
      on the reason of their non-operationality (presumption "apomorphic state
      corresponds more effective adaptation") or insufficient ontological grounds
      (presumptions "are more complex structure is apomorphic", "the most parsimonious
      cladogram is preferable", and "one should considered every to be inherited").

PMID- 15859452
TI  - Nitrogen and photosynthetic function of hermatypic corals. Oxygen exchange of
      Stylophora pistillata coral under artificial feeding.
AB  - The change of Stylophora pistillata coral photosynthetic function (oxygen
      exchange and biomass of symbionts) under starvation and food enrichment was
      studied to understand the role of heterotrophy in nitrogen supplements of
      zooxanthellae. The starvation caused the decrease of frequency of zooxanthellae
      cells division in 7-10 times. The number of degraded algae cells increased in
      same proportion and, as a result, the density of zooxanthellae in corals
      decreased about two times during one-two weeks. Under starvation corals kept
      their photosynthetic capacity at the level of corals in situ by means of
      enhancing the zooxanthellae gross photosynthesis. The respiration rate of coral
      had tendency to increase and the dry mass of polyp tissue to decrease. Under
      artificial feeding which was following starvation the zooxanthellae density
      increased in 1.5-2 times, and particular food caused more intensive accumulation
      of zooxanthellae comparing to dissolved inorganic ammonium. The feeding regime
      did not affect dry mass of polyp tissue and chlorophyll content as well as
      respiration and gross productivity of the corals. The conclusion about high
      effectiveness of particular feeding for supplying symbiotic algae with nitrogen
      was made and trophic status of zooxanthellae in hospite was determined as
      unlimited by nitrogen.

PMID- 15859453
TI  - [Parameters adaptation in the populations models].
AB  - Ecology-evolutionary models of low dimensions were developed on the basis of
      competitive selection criteria. Dynamics of variables (number of individuals) and
      the search of evolutionary-stable values of parameters (biological
      characterictics of populations) were monitored in the suggested models. If the
      environmental temperature is changing periodically, the average (a) and width (d)
      of temperature tolerance range appears to be the important parameters. By model
      experiments it was established that stable values of temperature (a), favorable
      for development of highly specialized algae (d is low) were close to minimum and
      maximum of temperature curve. And for the low specialized algae (d is high) this
      values were close to the average temperature of environment. In a similar manner,
      a set of evolutionally stable parameters (a, d) was established for either of the
      two interacted populations (competitors and "predator-prey"). The hypotheses
      concerning it's geometric structure and the process of coevolution is formulated.

PMID- 15859454
TI  - [Altricial and precocial developmental features in modern meat-type chicks].
AB  - Variability of egg weight, egg yolk content, neonatal growth rate and
      relationships of these parameters were studied in meat-type chicks. As it had
      been established the level of variability in neonatal growth traits was greater
      than variability of the egg morphology parameters. Egg weight had stronger
      influence on the chicks' neonatal growth rate than egg yolk content did. Low egg
      size was associated with limited neonatal growth rate variability, declined chick
      weight at hatching and increased relative growth rate throughout four days post
      hatch. Comparison of egg morphological parameters in two species having the same
      female definitive body weight--meat-type domestic fowl (precocial type) and brown
      pelican (altricial type) has shown, that, in contrary to predicted on the basis
      of avian developmental typology, egg weight to female body ratio was greater in
      brown pelican, egg yolk content was equal in both species.

PMID- 15859455
TI  - [Effect of water stress on the photosynthetic apparatus of plants and the
      protective role of cytokinins: a review].
AB  - Characteristics of photosynthetic apparatus (the pool of pigments and proteins;
      the activity of photosystems; the intensities of in vivo photoassimilation of
      carbon dioxide and in vitro activity of enzymes of carbon metabolism; leaf
      structure; chloroplast structure), undergoing changes under the conditions of
      water deficiency, have been reviewed. The protective role of cytokinins is due to
      their regulatory effects on the renewal of disrupted cellular structures, the
      condition of the stomata, and de novo synthesis and activation of proteins that
      are required for increasing plant resistance to water stress.

PMID- 15859456
TI  - [Characterization of peroxidase-catalyzed oxidation of chromogenic substrates by
      tetrazole and its 5-substituted derivatives].
AB  - Peroxidase-catalyzed oxidation of 2,2-azino-di(3-ethyl-benzthiazolydine-6
      sulfonic acid) (ABTS) and 3,3',5,5'-tetramethylbenzidine (TMB) is activated by
      tetrazole and its 5-substituted derivatives--5-amino-(AmT), 5-methyl- (MeT), 5
      phenyl- (PhT), and 5-CF3- (CF3-T) tetrazoles. In phosphate-citrate or phosphate
      buffer (pH 6.4 or 7.2; 20 degrees C), the activating effect of tetrazoles on TMB
      and ABTS oxidation decreased in the series AmT > MeT > T > PhT > CF3-T and T >
      AmT > MeT > PhT, respectively. The (coefficient) degree of activation (alpha),
      expressed in M(-1), determined for both substrates and all activators, depended
      on substrate type, buffer nature, and pH (it increased as pH increased from 6.4
      to 7.2). For TMB oxidation, good correlation between lgalpha and the Hammet
      constants sigma(meta) for m-substituents in the benzene series NH2, CH3, C6H5,
      and CF3 was found. It is suggested that AmT, MeT, and T can be used as activators
      of peroxidase-catalyzed oxidation of TMB and ABTS, as well as in designing
      peroxidase-based biosensors.

PMID- 15859457
TI  - [Purification and properties of serine proteinases from European catfish Silurus
      glanis L. pancreas].
AB  - Three trypsin isoforms (designated as T1, T2, and T3), three chymotrypsin
      isoforms (Kh1, Kh2, and Kh3), and two elastase isoforms (E1 and E2) were isolated
      from the pancreas of European catfish Silurus glanis L. by salting out with
      (NH4)2SO4, gel chromatography on Sephadex G-75, and ion exchange chromatography
      on DEAE cellulose. Isoelectric points of the enzymes, determined by isoelectric
      focusing, amounted to 4.42 for T1, 5.64 for T2, 6.90 for T3, 4.93 for Khl, 5.23
      for Kh2, 6.18 for Kh3, 6.17 for E1, and 8.48 for E2. Molecular weights of
      proteinases within each group were close and amounted to 30100 Da for trypsins,
      39800 Da for chymotrypsins, and 24000 Da for elastases. The enzymes isolated
      displayed maximal activities at alkaline pH values. Inhibitor analysis
      demonstrated that all the proteinases isolated from European catfish pancreas
      belonged to the serine type.

PMID- 15859458
TI  - [Thermostabilities of plant phenol oxidase and peroxidase, determining the
      technology of their use in food industry].
AB  - Stabilities of phenol oxidase and peroxidase from tea plant (Camellia sinensis
      L.) clone Kolkhida leaves, apple (Malus domestica L.) cultivar Kekhura fruits,
      walnut (Juglans regia L.) green pericarp, and horseradish (Armoracia lapathifolia
      Gilib) roots were studied using different storage temperature modes and storage
      duration. It was demonstrated that both enzymes retained residual activities
      (approximately 10%) upon 20-min incubation at 80 degrees C. Phenol oxidases from
      tea, walnut, and, especially, apple, as well as tea peroxidase were stable during
      storage. A technology for treatment of plant oxidases was proposed, based on the
      use of a natural inhibitor phenol oxidase and peroxidase, isolated from tea
      leaves, which solving the problem of residual activities of these enzymes,
      arising during pasteurization and storage of beverages and juices. It was
      demonstrated that browning of apple juice during pasteurization and beer
      turbidity during storage could be efficiently prevented using the natural
      inhibitor of these enzymes.

PMID- 15859459
TI  - [Cross-effects of extracellular factors of adaptation to stress in Luteococcus
      casei and Saccharomyces cerevisiae].
AB  - Saccharomyces cerevisiae yeasts (lower eukaryotes) were shown to produce a
      protein exometabolite with reactivation activity. We demonstrated cross-effects
      of extracellular protein factors of adaptation to stress (heat and UV
      irradiation) in yeasts and Luteococcus casei bacteria. The possibility for
      isolation and partial purification of protein exometabolites from the culture
      liquid of yeasts and bacteria by similar methods, as well as the similarity of
      elution profiles for the active proteins in high-performance liquid
      chromatography, suggests that the proteins (or fragments thereot) of the
      organisms studied are homologous.

PMID- 15859460
TI  - [Application of molecular systematics to study of bacterial cultures consuming
      volatile organic compounds].
AB  - A range of species of four mixed bacterial cultures was studied by molecular
      systematics methods with the use of 16S rRNA genes. The cultures had been
      developed for application in minireactors, to degrade volatile organic compounds
      (VOCs): ethyl benzene, m-xylene, styrene, and o-xylene. A sample of 30 plasmid
      rDNA clones was obtained for each of the mixed cultures. The clones were analyzed
      by RFLP according to two restriction sites. Major variants of the 16S-rDNA
      sequences, corresponding to the most abundant species, were determined for each
      association. Sequencing of four clones of predominant 16S-rDNAs showed that the
      culture consuming ethyl benzene was dominated by Pseudomonas fluorescens; o
      xylene, by Achromobacter xylosoxydans; styrene, by Pseudomonas veronii; and m
      xylene, by Delftia acidovorans. Minor components of all four cultures were
      generally similar. They included species of the genera Sphingobacter, Rhizobium,
      Mesorhizobium, Pedobacter, and Paenibacillus. Sampling sequencing of genes for
      16S rRNA cloned from total genomic DNA allowed quantitative determination of the
      composition of actual bacterial associations consuming VOCs in minireactors.

PMID- 15859461
TI  - [Isolation and study of azobenzene converting soil bacteria].
AB  - Heterotrophic bacteria were isolated from soil and glass slides and classified as
      Bacillus cereus SNK12, Paenibacillus polymyxa SNK2, Azotobacter chroococcum
      ANKII, and Ochrobacterium intermedium ANKI. Their cultures could degrade
      azobenzene under the conditions of co-metabolism. A rapid test for the ability of
      bacteria to convert azobenzenes is proposed.

PMID- 15859462
TI  - [Increase in tylosin production by a commercial strain of Streptomyces fradiae].
AB  - Conventional mutagenesis (UV irradiation and exposure to nitrosoguanidine) were
      used to produce and regenerate protoplasts, aiming at increasing the antibiotic
      activity of a Streptomycesfradiae strain producing tylosin. Variants exceeding
      the activity of the initial producer strain by 0.5-28.3% were obtained. The most
      active variants were produced by a combined exposure to UV and nitrosoguanidine,
      as well as upon regeneration of protoplasts formed from the cells of clones
      produced by UV irradiation. Unstable inheritance of the trait of increased
      tylosin production was demonstrated.

PMID- 15859463
TI  - [Polysaccharides of Ganoderma lucidum: factors affecting their production].
AB  - The conditions of polysaccharide production by the fungus Ganoderma lucidum were
      optimized. The maximal yield of endopolysaccharides and exopolysaccharides was
      observed at 25-30 degrees C, initial pH of culture medium 4.0-6.0, and at a C : N
      ratio of approximately 18 : 1 and 25 : 1, respectively. The greatest yield of
      mycelium was reached at a more intensive aeration, and the maximal yield of
      polysaccharides was observed at a less intensive aeration. The optimal ratio
      between fungus growth and polysaccharide production was observed at 100 rpm and
      an aeration of 1.0-1.5 1/1 medium min.

PMID- 15859464
TI  - [Effect of culture medium composition on the activity of extracellular lectins of
      Lentinus edodes].
AB  - The time course of lectin production in culture liquid of the basidial fungus
      Lentinus edodes strain F-249 in different media under the conditions of submerged
      culture was studied. The activity of agglutinins depended on the ratio between
      carbon and nitrogen sources and pH of culture medium. The activity of lectin in
      culture medium was maximal when the fungus was grown in a medium containing L
      arabinose as a source of carbon and L-asparagine as a source of nitrogen (C : N
      ratio, (9.5-12): 1)) on the day 15-18 of culturing at pH 8-9.

PMID- 15859465
TI  - [Selection and properties of mutant yeast Pichia guilliermondii strains resistant
      to chromium (VI)].
AB  - Yeast Pichia guilliermondii strains L3 and L2, exposed to UV mutagenesis,
      produced over 80 mutants capable of growing on media containing 1.5 mM bichromate
      (Cr(VI)). The mutations making the strains resistant to Cr(VI) were dominant or
      semidominant. The mutants varied in Cr(VI) resistance, the degree of chromium
      accumulation in the cells (from 0.1 to 11.6 mg/g dry cells), and the degree of
      Cr(VI) reduction (from 50% to complete disappearance of bichromate from the
      culture liquid). Chromium accumulation in mutant cells depended on medium
      composition, Cr(VI) concentration, and the time of exposure to Cr(VI). The
      resistance to bichromate can be caused by various reasons: decrease in chromium
      absorption, altered ability to reduce Nr(VI), or damage of sulfate transport
      mechanisms.

PMID- 15859466
TI  - [Studies of hydrolytic activity of enzyme preparations of Penicillium and
      Trychoderma fungi].
AB  - Enzyme preparations were isolated from the culture liquid of five mutant strains
      of the cellulase producer Penicillium verruculosum. The hydrolytic activities of
      these preparations against unbleached eucalypt cellulose was compared to that of
      commercial preparations of Trichoderma reesei (T. longibrachiatum). In the
      majority of cases, P. verruculosum enzymes provided higher yields of reducing
      sugars (RSs) and glucose. A correlation was found between the yield of RSs and
      the avicelase activity of the preparations in the reaction mixture.

PMID- 15859467
TI  - [Polysaccharides of diatoms occurring in Lake Baikal].
AB  - Polysaccharide composition of neutral, acid- and alkali-soluble fractions of the
      diatoms Stephanodiscus meyerii Genkal et Popovsk and Aulacoseira baicalensis (K.
      Meyer) Simonsen of Lake Baikal has been studied. Neutral polysaccharides were
      represented by chrysolaminarans (1-->3;1-->6-beta-D-glucans). The chrysolaminaran
      from S. meyerii consists of the high- and low-molecular-weight fractions (40 and
      2-5 kDa, respectively) and contains a large number of beta-1-->6-bound glucose
      residues. The chrysolaminaran from A. baicalensis is a low-molecular-weight 1-
      >3:1-->6-beta-D-glucan containing a small number of beta-1-->6 bonds, with
      mannitol being attached to the reducing unit of its chain. Acid- and alkali
      soluble polysaccharide fractions are practically absent in S. meyerii. The alkali
      soluble fraction from A. baicalensis is a low-molecular-weight (2-kDa)
      glycoprotein, the carbohydrate moiety of which is represented by a
      heteropolysaccharide.

PMID- 15859468
TI  - [Effect of aluminum and iron on lipid metabolism in aquatic invertebrates].
AB  - Methods of thin-layer, gas-liquid, and liquid chromatography were applied to the
      study of the effect of various concentrations of aluminum and iron salts on the
      contents of phospholipids, cholesterol, and fatty acids in the aquatic
      invertebrate Hydropsyche contubernalis L. (Trichoptera). It was found that the
      effect of the metals under study on lipid contents in living organisms depended
      on the composition of the aqueous medium and concentrations of the metals.
      Aluminum and iron altered the value of the cholesterol-to-phospholipid molar
      ratio. In the absence of lethal effects, this was indicative of attempts to
      switch adaptational biochemical mechanisms to stabilize cellular structures.

PMID- 15859469
TI  - [The use of liposomes for detection of the surface lipopolysaccharide antigen,
      Vibrio cholerae cells, and antibodies against them].
AB  - A test system for determination of Vibrio cholerae cells, surface O-antigen, and
      antibodies against them was developed on the basis of complement-dependent lysis
      of liposomes sensitized by the lipopolysaccharide-dependent antigen from Vibrio
      cholerae 569B. The factors that affect the function of the liposomal reagent were
      studied, and the conditions for detecting antibodies and antigenic material were
      optimized. This system is highly specific and sensitive to be used for the
      determination of anticholeraic antibodies (30-50 times as effective as
      agglutination tests), lipopolysaccharide antigen (100 ng/ml, which corresponded
      to 3.0 ng of lipopolysaccharide in the sample studied), and Vibrio cholerae cells
      (3.3 x 10(7) m.b./ml, which corresponded to 10(6) m.b. in sample). It takes 30-40
      min to detect the lipopolysaccharide antigen and 90 min to detect V. cholerae
      cells.

PMID- 15859470
TI  - [Enzyme immunoassay of immune complexes formed in vitro via interactions of serum
      antibodies with diphtheria toxin].
AB  - The interaction of diphtheria toxin with serum antitoxin antibodies has been
      studied by enzyme immunoassay at variable ratios of the original amounts of the
      antigen and antibodies in the reaction mixture. Under the conditions of excess of
      the antibodies, the free toxin is not detected, and free antibodies account for
      68 to 98% of the original amount. Under the conditions of excess of the toxin,
      free antibodies account for 2 to 7% of the original amount and free toxin, for 80
      100% of its original level. Under the conditions where the toxin is taken in
      excess, and the amounts of the toxin and the antibodies are equivalent, formed
      immune complexes are regularly detected in the reaction mixtures. In these
      complexes, part of the epitopes of the toxin remains free from antibodies. The
      data obtained are interpreted from the viewpoint of epitope heterogeneity,
      bivalency of serum antibodies, and monovalency of the toxin epitopes. A new model
      of the toxin-antibody interactions is proposed.

PMID- 15859471
TI  - [Growth-regulating activity of N-benzyl- and O-benzyl-containing compounds
      belonging to a new group of synthetic analogues of natural auxins].
AB  - We studied the effect of benzylamine, benzyl alcohol, and their derivatives
      (constituting a new group of synthetic analogues of natural auxins) on rooting of
      leaf and stem cuttings, rhizogenesis and growth of barley plantlets and tomato
      seedlings, and tomato plant productivity. These compounds promoted rooting of
      leaf and stem bean cuttings, increased rhizogenic activity, and stimulated the
      development of root systems in barley and tomato seeds. The activity of the
      compounds studied was similar to that of standard substances (3-indoleacetic acid
      potassium salt and 2-naphthylacetic acid). The benzyl group attached to the
      oxygen or nitrogen atom was shown to be the smallest molecular structure which
      provided auxin activity of the compounds. Derivatives of benzyl alcohol
      containing the quaternary ammonium fragment possessed auxin and anti-gibberellin
      (retardant) properties. They were selected by chemical synthesis of low-molecular
      weight bioregulators with desired properties (a combination of chemical fragments
      with complementary physiological activity in the molecule). Auxin and anti
      gibberellin (retardant) activities produced a synergistic effect. Germination of
      seeds treated with these compounds was accompanied by a more significant increase
      in the weight and length of roots (compared to standard auxins). The rate of
      seedling establishment reached 100%. The development of fruits and accumulation
      of reserve nutrient substances were synchronized and accelerated after spraying
      vegetating plants with solutions of studied compounds. The synergistic effect
      underlay a significant increase in the amount and quality of the crop (e.g.,
      tomatoes).

PMID- 15859472
TI  - [Biosensors 2004: the eight world Congress on biosensors].

PMID- 15859473
TI  - [Apoptosis and differentiation of epidermal keratinocytes].
AB  - We compared some processes characteristic for both apoptosis and terminal
      differentiation of epidermal keratinocytes. It can be proposed that nonapoptotic
      programmed cell death takes place during differentiation of keratinocytes.
      Apoptosis and terminal differentiation of keratinocytes appear to be different
      processes but some similar molecular mechanisms are involved in these processes.

PMID- 15859474
TI  - [Basic principles of terminal flower formation].
AB  - Studies of efflorescences of the mutants bractea and terminal flower1 and double
      mutant bra tfl1 of Arabidoipsis thaliana (L.) Heynh. have shown that the presence
      of a developed leaf in the node preceding the terminal flower is a necessary
      condition for the formation of the terminal flower perianth. This means that
      perianth cannot develop in an abracteose efflorescence of terminal flower. The
      second necessary condition for the terminal flower formation is a sufficient
      level of expression of the genes responsible for floral morphogenesis.
      Combination of these two conditions suffices for the development of a terminal
      flower with perianth. Since the general principles of organization are close for
      most flower plants, it can be stated that if the abracteose efflorescence is
      terminated by a flower with perianth, this is a consequence of forcing the
      lateral flower into the terminal position.

PMID- 15859475
TI  - [Aminotransferases in early development of salmonid fish].
AB  - The activities of alanine and aspartate aminotransferases were assessed in the
      embryos and juveniles of the rainbow trout Parasalmo mukiss L. and chum salmon
      Oncorchyncus keta W. Changes in subcellular localization of these enzymes and
      their activities were found at different pH optima in each subcellular fraction
      of the rainbow trout during ontogenesis.

PMID- 15859476
TI  - [Activation of nucleolar organizers during in vitro cultivation of mouse R1
      embryonic stem cells].
AB  - We studies the activities of ribosomal genes (nucleolus forming regions of
      chromosomes) at successive stages of cultivation of the mouse R1 embryonic stem
      cells. The total number and number of active nucleolar organizers were estimated
      by means of in situ hybridization with mouse rDNA probes and argentophilic
      staining of nucleolus forming chromosomes regions from the 16th until the 32nd
      passages. The data we obtained suggest that the total number of nucleolar
      organizers per metaphase plate was constant (as a rule, eight), while the mean
      number of active nucleolar organizers progressively increased from the early
      (16th) to the late (32nd) passages: 5.2 +/- 0.4 versus 7.4 +/- 0.9 argentophilic
      organizers per cell. Cell heterogeneity by the number of active nucleolar
      organizers also increased during the late passages. Taken together, these data
      suggest activation of DNA transcription and synthesis of ribosomes during
      cultivation of mouse R1 embryonic stem cells. Based on the experimental and
      published data, it has been proposed that activation of ribosomal genes
      correlates in time with a decreased capacity of embryonic stem cells for
      pluripotent differentiation.

PMID- 15859477
TI  - [Comparison of variability of Rana temporaria (Amphibia, Anura) gastrula from
      different populations developing under the conditions of antropogenic pollution].
AB  - The gastrulation of Rana temporaria embryos was studied at the natural spawning
      sites of Moscow city and Moscow district by means of morphometric analysis. We
      demonstrated that anthropogenic pollution plays an important role in
      morphogenesis of Anura. The measurements of embryos from the Moscow ponds made it
      possible to show an increased variability of gastrulation. Moreover, the level of
      gastrulation variability depends on the degree of pollution of a spawning pond
      and is coupled with increased correlations between the morphological features.
      This increase of correlations could be due to: (1) an increased number of
      correlating features (appearance of new correlations) and (2) strengthening of
      the existing correlations. The first way makes the gastrulation process more
      coordinated, and the second one causes the appearance of morphological
      structures, which are normally formed only at the next developmental stages.

PMID- 15859478
TI  - [Electron probe microanalysis of potassium and phosphorus in mouse oocytes and
      zygotes].
AB  - Intracellular concentrations of potassium and phosphorus were determined by
      Electron Probe Microanalysis in mouse mature oocytes and zygotes. The oocytes
      were characterized by insignificant variations in the concentrations of these
      elements in the cytoplasm: 60 +/- 4 and 103 +/- 6 mM, respectively. In zygotes,
      on the contrary, significant variations were observed: 64 +/- 16 and 84 +/- 14
      mM, respectively. Changes in the potassium homeostasis during the first cell
      cycle have been discussed.

PMID- 15859479
TI  - [Characteristics of microsporogenesis in the Siberian larch growing under the
      conditions of technogenic load].
AB  - Studies of microsporogenesis in the Siberian larch growing in Krasnoyarsk and its
      suburbs have shown that meiosis starts in October. Microsporocytes winter at
      prophase I (leptoneme, diploneme). Reduction divisions in male generative buds
      are resumed and terminated in spring, in March. However, in the case of thaws
      during the autumn-winter period, meiotic division proceeds in the larch buds and
      this leads to the formation of degrading tetrads and pollen. Hence, the organic
      quiescence is absent in the larch in winter. It was shown that in the larch
      growing in the city, meiosis proceed more asynchronously than in the background
      tree stands. An increase of chromosomal aberrations during the reduction division
      was noted under the conditions of technogenic pollution.

PMID- 15859480
TI  - [Development of the mitochondrial apparatus and blood supply of skeletal muscle
      fibers during ontogenesis of domestic fowl].
AB  - The diameter, length, and numerical density of capillaries, diameter of muscle
      fibers, size and numerical density of their profiles, and relative volume of
      mitochondria in them were determined in the chicken red oxidative gastrocnemius
      and white glycolytic pectoral muscle during development from day 10 of
      embryogenesis to six month of postnatal life. The bulk blood flow was measured in
      these muscles by hydrogen clearance during postembryonic development. During
      embryogenesis, the fibers of gastrocnemius muscle develop and grow at a higher
      rate, while during postembryonic development, those of the pectoral muscle
      develop faster. The density of mitochondrial profiles increases during
      embryogenesis and decreases after hatching, while their mean size increases,
      especially in the oxidative fibers, but it somewhat decreases in 6-month old
      chicks. Redistribution of mitochondria by the fiber section during development
      takes place in both muscles: they are localized predominantly in the center in 18
      day embryos and in the periphery, especially in the gastrocnemius fibers, in 6
      month old fowl. At hatching, the lengths of capillaries are similar in both
      muscles, but as chicks grow, the proportion of longer (more than 600 microm)
      capillaries in the pectoral muscle sharply increases, while their density and
      bulk blood flow decrease. Ratios were determined between structural parameters of
      the capillary bed and mitochondria, on the one hand, and oxygen consumption
      (ml/min per 1 mm fiber and 100 g muscle mass), on the other.

PMID- 15859481
TI  - [Effects of growth factors FGF4, TGFalpha, and TGFbeta1 on the development of
      parthenogenetic embryos of C57BL/6 mice].
AB  - We studied the effects of three growth factors, fibroblast growth factor (FGF4),
      transforming growth factor alpha (TGFalpha), and transforming growth factor beta1
      (TGFbeta1), on development of diploid parthenogenetic embryos of C57BL/6 mice,
      which are not capable of developing to somatic stages. Parthenogenetic embryos
      were treated with growth factors at optimal doses in vitro at the morula-
      blastocyst stages and transplanted in the uterus of pseudopregnant females. FGF4
      and TGFalpha improved the development of parthenogenetic embryos at the
      preimplantation stages and the number of blastocysts increased under the
      influence of TGFalpha. All three growth factors improved the implantation of
      embryos in the uterus. When FGF4 or TGFbeta1 were added to the nutrient medium,
      2.4 or 1.6%, respectively, of parthenogenetic embryos reached the somatic stages
      in utero. No somitic embryos were observed in the control. The treatment of
      parthenogenetic embryos with two growth factors, FGF4 and TGFbeta1,
      simultaneously increased the amount of somatic embryos to 7.5%, while combination
      of three growth factors in creased the amount of such embryos to 16.7%. In the
      latter case, some parthenogenetic embryos reached the stage of 25-27 pairs of
      somites and were 2.0-2.5 mm long. The data we obtained suggest that, when
      combined, the growth factors FGF4, TGFalpha, and RGFbeta1 possessed a synergistic
      effect leading to a significant improvement of the development of parthenogenetic
      C57BL/6 embryos.

PMID- 15859482
TI  - [Visible and "cryptic" segregation of parental chromosomes in embryonic stem
      hybrid cells].
AB  - Chromosome segregation of the parental chromosomes was studied in 20
      interspecific hybrid clones obtained by fusion of Mus musculus embryonic stem
      cells with Mus caroli splenocytes. FISH analysis with labeled species specific
      probes and microsatellite markers was used for identification of the parental
      chromosomes. Cytogenetic analysis has shown significant intra- and interclonal
      variability in chromosome numbers and ratios of the parental chromosomes in the
      hybrid cells: six clones contained all M. caroli chromosomes, nine clones showed
      moderate segregation of M. caroli chromosomes (from 1 to 7), and five clones
      showed extensive loss of M. caroli chromosomes (from 12 to complete loss of all
      M. caroli autosomes). Both methods demonstrated "cryptic" segregation of the
      somatic partner chromosomes. For instance, five clones with near-tetraploid
      chromosome sets contained only few M. caroli chromosomes (from 1 to 8). The data
      obtained suggest that the tetraploid chromosome set per se is not a sufficient
      criterion for conclusion on the absence of chromosome loss in the hybrid cells.
      Note that "cryptic" chromosome segregation occurred at a high frequency in the
      examined hybrid clones. Thus, "cryptic" segregation should be borne in mind for
      assessing pluripotency and genome reprogramming of embryonic stem hybrid cells.

PMID- 15859483
TI  - How PAs live and work.

PMID- 15859484
TI  - Physician assistant volunteers belong in free clinics.

PMID- 15859485
TI  - Nerve entrapments of the wrist: early treatment preserves function.
AB  - Nerve entrapment syndromes may affect as many as one in four office workers.
      Prompt diagnosis is critical to the selection of an appropriate and effective
      treatment.

PMID- 15859486
TI  - Severe GERD: effective treatment prevents potentially serious complications.
AB  - When left untreated--or when treated inadequately--severe gastroesophageal reflux
      disease can progress to esophagitis, ulcers, laryngeal disease, chronic cough,
      Barrett's esophagus, and esophageal adenocarcinoma.

PMID- 15859487
TI  - Barriers for PAs volunteering to serve indigent populations.
AB  - Lack of liability coverage and authorization requirements for supervision can
      create legal barriers for PAs who want to volunteer. The good news: Some states
      are amending their laws so that PAs can volunteer legally.

PMID- 15859488
TI  - Medical management of the adult patient with Down syndrome.
AB  - Longer life expectancy and relative independence among people with Down syndrome
      mean a unique ambulatory population for the family practice setting. How can you
      best address the medical needs of these patients?

PMID- 15859489
TI  - A fresh look at clinical excellence.

PMID- 15859490
TI  - Diagnostic challenges from your case files. Giant cell tumor.

PMID- 15859491
TI  - On a roll. RFID moves toward patient safety.

PMID- 15859492
TI  - The particulars on particulates. Taking measures to eliminate lint on
      instruments.

PMID- 15859493
TI  - A quality example. What it takes to receive the Malcolm Baldridge Award.

PMID- 15859494
TI  - Sticking to OSHA guidelines.

PMID- 15859496
TI  - Still plenty of opportunity for reductions in inpatient LOS.

PMID- 15859495
TI  - Use combined drug, diagnostic data to improve cost forecasts.

PMID- 15859497
TI  - Detailed data reflect PMPM costs for Pennsylvania's Medicaid program.

PMID- 15859498
TI  - As higher enrollment drives Medicaid growth, can prepaid plans rein in costs?

PMID- 15859499
TI  - [Infection syndrome in acute radiation sickness patients subjected to Chernobyl
      accident].
AB  - In spite of intensive antimicrobial prophylaxis and therapy, most patients with
      acute radiation sickness I-IV severity grade (dose of 0.1-13.7 Gy) developed
      infections caused by bacteria, fungi and viruses. Frequency and intensity of
      those infections were proportional to the radiation dose and severity grade of
      radiation sickness.

PMID- 15859500
TI  - [Long-term response of bronchopulmonary system in liquidators of Chernobyl
      accident].
AB  - Liquidators of chernobyl accident consequences were subjected to simultaneous
      external gamma-beta-radiation and inhalation of particles containing radionuclide
      aerosols and nonradiation toxic chemicals. findings are typical defects of the
      liquidators examination: assignment of individuals with pulmonary disorders to
      post-accident work, misinterpretation of the disease severity with
      underestimation of previous occupational anamnesis and aggravating role of
      nonradiation.

PMID- 15859501
TI  - [Results of peripheral blood tests in thorium production workers].
AB  - The authors studied peripheral blood parameters in thorium production workers.
      Separate analysis covered a group of subjects with chronic radiation sickness.
      Reliably more pronounced in the chronic radiation sickness group, disposition to
      thrombocytopenia and leucopenia could be caused by occupational factors. Anemia
      associated with disposition to erythrocytopenia and increased ESR could be caused
      by malnutrition.

PMID- 15859502
TI  - [Genesis under occupational exposure to toxic and radiation hazards].
AB  - The authors studied frequency, periods of development and morbidity structure of
      malignances among chronic uranium intoxication patients. tumors were diagnosed in
      19.1% of the cases. Neoplasms developed in the presence of uranium intoxication
      symptoms in 57.8% of the patients, occurred after the occupational disease was
      ruled out in 42.2% of the cases. The oncologic morbidity structure was presented
      mostly by tumors of gastro-intestinal tract (33.3%) and respiratory system (20%).

PMID- 15859503
TI  - [Periods of cardiovascular diseases development in individuals with chronic
      radiation sickness caused mainly by external uniform radiation].
AB  - The author analysed files of 101 patients suffered from chronic radiation
      sickness due to chronic occupational mainly external radiation (dose of 98 to 947
      cGy). Through represented clinical diagnoses, the author studied age of primary
      diagnosis of ischemic heart disease, cerebrovascular diseases in general and of
      individual entities, arterial hypertension, relationships between age at the
      diagnosis and total radiation dose, dose rate. The article presents comparative
      data on dose loads, time of various cardiovascular diseases diagnosis in
      accordance with circulatory disorders during chronic radiation sickness.

PMID- 15859504
TI  - [Long-term (45-50 years) follow-up concerning medical and social status of
      patients with chronic radiation sickness].
AB  - The article covers evaluation of medical and social status in 673 subjects who
      suffered from chronic radiation sickness. By 45-50 years of follow-up, nearly 70%
      of the subjects had primary disablement established after the age of 60. Main
      causes of the disablement were cerebrovascular diseases and malignances.
      Increasing values of primary disablement in chronicradiation sickness patients
      over able-bodied age match increasing primary disablement among the country's
      general population and result from not only medical but also social matters.

PMID- 15859505
TI  - [Hygienic criteria for allowable residual activity of radioactive nuclides after
      decontamination].

PMID- 15859506
TI  - [Clinical evaluation of tolerance and efficiency of Cinkocin medication for human
      incorporation of plutonium and americium].
AB  - The authors represent data on studies of tolerance and efficiency of Cinkocin
      administered to 18 patients who had occupational exposure to plutonium and
      americium.

PMID- 15859507
TI  - [Emergency care for acute wound entering of plutonium and americium into the body
      (real case)].
AB  - The article describes a case of slowly soluble plutonium and americium compounds
      entering human body via skin wound. During the wound healing, the authors
      followed features of biokinetics of the radioactive substances, determined the
      major route of their excretion, evaluated efficiency of surgical d-bridement and
      complexation medicine (pentacin). clinical and biophysicdata collected could
      serve to increase efficiency of urgent therapeutic and prophylactic measures
      aimed to individuals with wounds contaminated with radioactive substances.

PMID- 15859508
TI  - Chemical sensitivity in symptomatic Cambodia veterans.
AB  - Following their participation in a United Nations peacekeeping operation in
      Cambodia (1992-1993), Dutch veterans complained of symptoms similar to those
      reported by Gulf War veterans. The authors conducted a matched case-control study
      to evaluate 76 symptomatic and 32 matched asymptomatic Cambodia veterans on the
      basis of data collected by postal questionnaire. The number of symptomatic
      veterans who reported having used insect repellants that contained N,N,-diethyl
      meta-toluamide (DEET) during the mission in Cambodia was significantly higher,
      compared with asymptomatic veterans. The percentage of veterans who reported
      feeling ill following brief exposures to chemicals such as paint or pesticides
      was equal in both groups, but the percentage was low compared with the results of
      other studies of Multiple Chemical Sensitivity Syndrome. The current study was
      limited by self-report and time delay (potential recall bias) between deployment
      to Cambodia and the time of survey. Nevertheless, the study results did not
      support the hypothesis that symptoms in the total group of Cambodia veterans
      could be related to Multiple Chemical Sensitivity Syndrome.

PMID- 15859509
TI  - Effects of chlorine and its cresylate byproducts on brain and lung performance.
AB  - Chlorine and potassium cresylate spilled from a train wreck forced evacuation of
      nearly 1000 people in and near the town of Alberton, Montana, in 1996. Because
      respiratory and other symptoms persisted in this population, neurobehavioral and
      pulmonary functions were evaluated in a cohort of exposed vs. unexposed
      individuals. Ninety-seven subjects were tested 7 wk after exposure. Three years
      later, 36 of the original subjects were retested, along with 21 new patients
      exposed in the same incident. These 57 were compared with 22 unexposed
      individuals. Twenty-six neurobehavioral functions were tested, and spirometry was
      performed on each subject. At 7 wk postexposure, patients showed significant
      differences in 5 neurobehavioral functions (i.e., balance, simple reaction time,
      abnormal visual quadrants, vocabulary, and information), compared with the
      unexposed individuals recruited in 1999. Patients' Profile of Mood States scores
      and frequencies of 35 symptoms were also elevated, compared with the unexposed
      group. At 3 yr postexposure, patients exhibited differences in 7 additional
      neurobehavioral functions (i.e., choice reaction time, balance with eyes open,
      color errors, visual fields, Culture Fair, and verbal recall). Respiratory
      symptoms were increased, but pulmonary functions did not change. Exposure to
      chlorine and potassium cresylate produced neurobehavioral impairments that have
      been observed to increase across 3 yr. Spills in heavily populated areas could
      injure thousands, overwhelming medical facilities.

PMID- 15859510
TI  - Incidence of cancer in the vicinity of Korean AM radio transmitters.
AB  - Results of various studies have indicated a potential association between
      exposures to electrical and/or magnetic fields and risks of various cancers. The
      authors used a cross-sectional ecological study design to investigate such a
      potential association. In areas proximate to 42 amplitude modulated (AM) radio
      transmitters, 11 high-power study sites (i.e., areas exposed to 100-1500-kW
      transmission power) and 31 low-power study sites (i.e., areas exposed to 50-kW
      transmission power) were identified. The incidence of cancer within a 2-km radius
      of each transmitter was obtained from (a) Korean medical-insurance data for the
      years 1993 through 1996, (b) population census data for the year 1995, and (c)
      resident registration data for the year 1995. The authors calculated age
      standardized rate ratios for total cancer, leukemia, malignant lymphoma, brain
      cancer, and breast cancer, and compared the incidence of cancer within 2 km of
      the high-power transmitters vs. the incidence within 2 km of the low-power
      transmitters. Four control areas for each high-power transmitter were also
      selected. The control areas were located in the same, or nearest adjacent,
      province as the high-power sites, but were at least 2 km from any of the
      transmitters. Indirect standardized observed/expected ratios for the high-power
      sites vs. control areas were calculated for each transmitter separately, and for
      4 transmitter groupings defined by power level (i.e., 100 kW, 250 kW, 500 kW, and
      1500 kW). The authors found no significant increase in age-standardized rate
      ratios of cancers for high-power vs. low-power sites, with the exceptions of
      total cancer and of brain cancer in women. Among the 11 high-power sites, there
      were significantly increased incidences of leukemia in 2 areas and of brain
      cancer in 1 area. Future studies should incorporate additional detailed exposure
      assessments and a strong analytical study design to explore the possible
      association between radiofrequency radiation from AM radio transmitters and
      cancer.

PMID- 15859511
TI  - Health risk assessment for sulfur dioxide pollution in South Durban, South
      Africa.
AB  - Concern about health risks from sulfur dioxide (SO2) pollution prompted a health
      risk assessment for residents of the heavily polluted industrial region of South
      Durban, South Africa. The U.S. Environmental Protection Agency health risk
      assessment model was used to evaluate health effects for individuals in 4 age
      groups on the basis of data for a 3-yr period, from 1997-1999. Under normal
      exposure conditions, the level of risk was low (Hazard Quotient < 1); only under
      the worst-case scenario (exposure 24 hr/day) was there a significant risk of
      developing health effects. Inasmuch as these results are contrary to the
      popularly held belief that residents have a high risk of developing SO2-related
      respiratory diseases under normal exposure conditions, future studies should more
      thoroughly investigate exposure patterns and verify the authors' assumption that
      indoor SO2 levels are zero.

PMID- 15859512
TI  - Effect of a follow-up professional home cleaning on serial dust and blood lead
      levels of urban children.
AB  - Children residing in Philadelphia, Pennsylvania, who were enrolled in a clinical
      trial of oral chelation therapy (n=73) were studied to determine the effects of a
      follow-up professional lead dust cleaning of their homes 18 mo after an initial
      cleaning and commencement of therapy. Home dust lead levels were determined from
      dust-wipe specimens collected from the kitchen and playroom floors, and from a
      playroom windowsill, prior to, immediately following, and 3 and 6 mo after the
      second cleaning. Children's blood lead levels were assessed at 3-mo intervals
      before and after the follow-up cleaning. Professional cleaning produced immediate
      decreases in dust lead levels; however, dust lead re-accumulated to precleaning
      levels within 3-6 mo. Frequent, repeated cleanings may be required if blood lead
      or dust lead levels are to be reduced and sustained at low levels in urban homes.

PMID- 15859513
TI  - Workplace exacerbation of asthma symptoms: findings from a population-based study
      in Maine.
AB  - In this population-based study of asthma in the State of Maine, the authors
      investigated how often asthma symptoms were exacerbated in the workplace.
      Participants from 5 hospital service areas in Maine completed a telephone
      questionnaire. Of 474 adult participants (18-65 yr of age) employed during the
      preceding year and for whom information on occupation and industry was available,
      64 (13.5%) were identified with current asthma, including 28 (5.9%) with current
      physician-diagnosed asthma and 36 (7.6%) who met criteria for symptoms consistent
      with asthma. Jobs were identified a priori as "high-risk" or "low-risk" for
      asthma. Of the 64 asthma cases, 16 (25%) reported that their coughing or wheezing
      worsened at work. Among the symptom-based cases, the percentage with workplace
      exacerbation of asthma was elevated for high-risk jobs (7/14 = 50%) vs. low-risk
      jobs (3/22 = 13.6%) (p = 0.03). No similar elevation was observed for individuals
      with current physician-diagnosed asthma, which might have resulted, in part, from
      a healthy worker effect.

PMID- 15859514
TI  - Deaths from neoplasms and detection of radionuclides in excised human lungs in
      the Eordea Basin, Greece.
AB  - Lignite contains various trace-metal natural radioactive contaminants. In the
      Eordea Basin, the most important lignite field in Greece, the authors conducted a
      proportional mortality ratio (PMR) study that compared the mortality rates of
      individuals who lived in the basin vs. a control group who resided in the city of
      Kilkis, over a 30-yr period. The following information was used in the study: (a)
      municipal registrations of deaths from neoplasms during the period from 1971 to
      2000, and (b) detection of radioactive substances in samples obtained from
      excised lungs of individuals living in Eordea Basin who suffered from neoplasm.
      The corresponding registrations of deaths from neoplasm of the inhabitants of
      Kilkis, a city located outside the Eordea Basin, formed the control group. A
      diachronic increase of the PMR was detected as a result of neoplasms and,
      particularly, as a result of lung cancer in Eordea Basin. However, the above
      ratio did not exceed the corresponding PMR recorded in Kilkis. In 20 lung samples
      obtained from patients who had lived in Eordea Basin, and in 19 lung samples from
      patients in Kilkis, the activity of the radionuclides of uranium and thorium
      radioactive decay series, potassium-40, and cesium-137 was not higher than
      expected. No statistically significant difference was found between the
      inhabitants of the 2 regions, thus it was concluded that the increase in
      respiratory-system neoplasms was likely associated with the high prevalence of
      smoking among the regions' inhabitants. In future studies, a longer observation
      period and examination of more cases will be necessary to further investigate a
      possible association between radionuclides and lung neoplasms in the Eordea
      Basin.

PMID- 15859515
TI  - Detection of p16 hypermethylation in gastric carcinomas using a seminested
      methylation-specific PCR.
AB  - Aberrant DNA methylation of a CpG site is among the earliest and most frequent
      alterations in various tumors including gastric carcinoma. The aim of this study
      is to detect tumor-associated aberrant hypermethylation of the p16 gene from 60
      gastric tumor and corresponding normal tissues using a seminested methylation
      specific PCR (MSP). The results indicated that hypermethylation of the p16 gene
      could be detected in 80% (48/60) of the gastric tumor samples from the first PCR.
      However, the frequency increased significantly to 86.7% (52/60) of the gastric
      tumor samples after the second PCR. These results show that this technique
      increases the sensitivity of detecting p16 hypermethylation from tumor samples.
      Furthermore, the aberrant methylation of p16 was observed in all of the stages,
      confirming that this epigenetic alteration is an early event during gastric
      carcinogenesis. Clinicopathologic parameters such as age, sex, and histological
      differentiation of GC were not significantly associated with the methylation
      status.

PMID- 15859516
TI  - Allozymic polymorphism among 14 populations of the house mouse, Mus musculus
      domesticus, from Greece.
AB  - Nineteen loci from 239 individuals of the house mouse Mus musculus domesticus
      (Rodentia, Muridae) were analyzed by means of thin layer electrophoresis. The
      mice were collected from 14 localities of Greece mainly confined to the area of
      NW Peloponnese, where a Robertsonian (Rb) system is observed. The individuals
      were chromosomally characterized by nine diploid numbers, the 2n = 24, 26, 27,
      28, 29, 30, 31, 32, and 40. The statistic elaboration revealed that all 14
      populations studied were not characterized by cohesive demic structure and high
      inbreed levels while the gene flow among them has resulted in low levels of
      genetic differentiation. The resulting values for Nei's genetic distance
      corresponded to distances known for the level of geographical populations of M.
      musculus. Wagner's cladogram for the phylogenetic relations between the
      populations studied implied that it is the diploid number, rather than the
      geographical factor, that characterizes or dominates each population, which
      mainly influences the phylogenetic relationships.

PMID- 15859517
TI  - Molecular genetic analysis of QTLs for ferulic acid content in dried straw of
      rice (Oryza sativa L.).
AB  - Phenolic acids are secondary metabolic organic compounds produced by plants and
      often are mentioned as allelochemicals. This study was conducted to determine the
      genetic basis controlling the ferulic acid content of rice straw in a recombinant
      inbred (RI) population derived from a cross between a japonica variety,
      Asominori, with a higher content of ferulic acid, and an indica variety, IR24,
      with a lower content, using 289 RFLP markers. Continuous distributions and
      transgressive segregations of ferulic acid content were observed in the RI
      population, which showed that ferulic acid content in rice straw was
      quantitatively inherited. Single marker analysis and composite interval mapping
      identified three quantitative trait loci (QTLs) for ferulic acid content with LOD
      values of 2.03 (chromosome 3), 3.16 (chromosome 6), and 3.06 (chromosome 7); all
      three had increased additive effects (13.5, 18.3, and 18.1 microg g(-1)) from the
      Asominori parent and accounted for 5.5, 16.9, and 12.8% of total phenotypic
      variation, respectively. This is the first report on the identification of QTLs
      associated with ferulic acid and their chromosomal localization on the molecular
      map of rice. The tightly linked molecular markers that flank the QTLs might be
      useful in breeding and selection of varieties with higher phenolic acid content.

PMID- 15859518
TI  - Molecular analysis of the relatedness of five domesticated turkey strains.
AB  - Our knowledge of the genetic relatedness among the eight existing domesticated
      turkey strains is limited. To begin to address this paucity, genetic relatedness
      among five turkey strains (Blue Slate, Bourbon Red, Narragansett, Royal Palm, and
      Spanish Black) was investigated using three molecular marker systems: randomly
      amplified polymorphic DNA (RAPD), microsatellite, and SNPs derived from a
      sequence tagged site and a cloned RAPD fragment. The RAPD analyses were based on
      five primers that revealed a total of 14 informative DNA fragments in all five
      populations. The microsatellite analyses involved two informative alleles from
      three primer-pairs. A total of nine SNPs were detected, one of which appeared to
      be strain specific. This SNP formed the basis of a PCR-RFLP genotyping procedure
      developed to distinguish one of the strains from the other four. Evidence from
      these analyses including the SNP-based RFLP-PCR suggests that Royal Palm is
      distinct from the other four strains, though more closely related to
      Narragansett. These data provide, for the first time, molecular evidence of the
      potential relationships among noncommercial domesticated turkey strains.

PMID- 15859519
TI  - Isoenzyme variation in Melipona rufiventris (Hymenoptera: Apidae, Meliponina) in
      Minas Gerais State, Brazil.
AB  - The stingless bee Melipona rufiventris is an important pollinator in several
      Brazilian ecosystems. Originally widely distributed in Minas Gerais (MG) state,
      this species is becoming very rare. Therefore this species was included in the
      endangered species list of MG. We used isoenzyme data for a better understanding
      of the genetic structure of several M. rufiventris colonies. Samples of 35
      colonies were collected from 12 localities and evaluated by nine enzymatic
      systems, which yielded 17 loci. M. rufiventris genetic variation was found to be
      low, typical of an endangered species. The proportion of polymorphic loci was
      5.88% in both ecosystems. Only Est-4 was polymorphic in colonies from the Forest
      and Mdh-1 in colonies from the Cerrado. The expected heterozygosity ranged from
      0.0068 in the Cerrado to 0.0078 in the Forest. Despite this, enzyme
      electrophoretic analyses provided a good idea of the diversity between samples
      from Cerrado and Forest which reinforce the existence of two different "forms" of
      M. rufiventris in MG, one present in the Cerrado and the other in Forest. This
      information is of great importance for the conservation of M. rufiventris in MG.

PMID- 15859520
TI  - Cloning and characterization of a beta3 tubulin cDNA from the small brown
      planthopper, Laodelphax striatellus.

PMID- 15859521
TI  - Defective glycosaminoglycan substitution of decorin in a patient with progeroid
      syndrome is a direct consequence of two point mutations in the
      galactosyltransferase I (beta4GalT-7) gene.
AB  - The small dermatan sulfate proteoglycan decorin is involved in the regulation of
      collagen fibrillogenesis, cell adhesion and migration, and growth factor
      signaling. In a progeroid patient carrying two point mutations in beta4
      galactosyltransferase I (beta4GalT-7) only 50% of the decorin core protein
      molecules are substituted with glycosaminoglycan chains. We expressed decorin, as
      well as wild-type and mutant alleles of beta4GalT-7 in galactosyltransferase
      deficient CHO618 cells. Decorin was less efficiently substituted with
      glycosaminoglycan chains upon expression of beta4GalT-7(186D) compared to
      beta4GalT-7-expressing cells. Decorin from beta4GalT-7-expressing cells displayed
      increased molecular heterogeneity. Decorin glycosaminoglycan chains were
      completely susceptible to chondroitinase ABC treatment. Cells expressing
      beta4GalT-7(206P) did not synthesize the proteoglycanform of decorin. Thus, the
      beta4GalT-7 mutations directly affect the molecular phenotype of decorin observed
      in a patient with the progeroid form of Ehlers-Danlos syndrome, which may be a
      major mechanistic cause for the skin and wound healing defects observed in this
      patient.

PMID- 15859522
TI  - Assignment of the gene for porcine insulin-like growth factor binding protein 1
      to chromosome 18 and detection of polymorphisms in intron 2 by PCR-RFLP.
AB  - We have obtained a partial cDNA and three BAC clones for the porcine insulin-like
      growth factor binding protein 1 gene (IGFBP-1). Results of fluorescence in situ
      and radiation hybrid (RH) mapping assigned this gene to porcine chromosome (SSC)
      18q24-qter. We found two types of polymerase chain reaction-restriction-fragment
      length polymorphisms (PCR-RFLP) in intron 2 by using FokI and AluI.

PMID- 15859523
TI  - Randomized clinical trials in Clinical Rehabilitation.
AB  - A randomized clinical trial (RCT) is currently the strongest method for
      evaluating interventions in clinical practice. RCTs also provide the politically
      most powerful form of evidence. However it is not necessarily agreed what
      constitutes an RCT. This editorial explores what might be included within the
      rubric of 'randomized clinical trial' (and randomized controlled trial) by
      considering the reasons for using randomization and controls, and by discussing
      the definitions of clinical and trial. It suggests that the definition used in
      the Cochrane Glossary is too restricted and needs revision.

PMID- 15859524
TI  - Is inspiratory muscle training effective for individuals with cervical spinal
      cord injury? A qualitative systematic review.
AB  - OBJECTIVE: To perform a systematic review to determine the effect of inspiratory
      muscle training (IMT) in adults with cervical spinal cord injury (CSCI). DESIGN:
      A systematic search of the literature on IMT and CSCI according to the Cochrane
      Collaboration protocol was performed. We searched electronic databases up to
      August 2003 including MEDLINE and CINAHL, searched reference lists from pertinent
      articles and books, made personal contact with authors, and hand searched
      targeted journals to identify potential studies for inclusion. STUDY SELECTION:
      Inclusion criteria for the review included randomized controlled trials published
      in English comparing IMT with another comparison group among adults with CSCI.
      DATA EXTRACTION: Two reviewers abstracted relevant data from included studies.
      Methodological quality of the studies was assessed using criteria developed by
      Jadad et al. We also assessed whether the comparison groups were similar at
      baseline and whether an intention-to-treat analysis was performed. RESULTS: Forty
      articles were retrieved and three met the inclusion criteria. All studies used
      inspiratory resistance muscle trainers for at least 15 min, twice daily, five to
      seven days per week for six to eight weeks. Meta-analysis could not be performed
      due to differences in study design and outcomes. Only one study reported a
      positive effect of IMTcompared to control for measures of dyspnoea and pulmonary
      function. CONCLUSION: Literature on the effect of IMT among adults with CSCI is
      scarce and an overall effect could not be confirmed.

PMID- 15859525
TI  - Evidence of the efficacy of occupational therapy in different conditions: an
      overview of systematic reviews.
AB  - OBJECTIVE: To summarize the research evidence available from systematic reviews
      of the efficacy of occupational therapy (OT) for practitioners, researchers,
      purchasing organizations and policy-makers. DATA SOURCE: The search for
      systematic reviews was conducted in PubMed and the Cochrane Library (October
      2004). METHODS: The reviews included were those that utilized a systematic search
      for evidence with regard to OT for specific patient groups. Data were summarized
      for patient group, interventions, outcome domains, type of study designs
      included, method of data synthesis and conclusions. RESULTS: Fourteen systematic
      reviews were included. Three reviews related to rheumatoid arthritis, four
      reviewed stroke and four focused on elderly people. Reviews of Parkinson's
      disease, multiple sclerosis, Huntington's disease, cerebral palsy and mental
      illnesses were also identified. The reviews of rheumatoid arthritis, stroke and
      elderly people showed evidence of the efficacy of OT in increasing functional
      abilities. Positive results were presented for quality of life and social
      participation in elderly people and stroke respectively. The efficacy of OT in
      all other patient groups is unknown due to insufficient evidence. CONCLUSION:
      This summary shows that elderly people and people with stroke or rheumatoid
      arthritis can expect to benefit from comprehensive OT. Evidence of the efficacy
      of specific interventions is sparse and should be addressed in future research.
      The evidence that does exist should be incorporated into OT practice.

PMID- 15859526
TI  - Effect of pulsed short-wave diathermy on pain and function of subjects with
      osteoarthritis of the knee: a placebo-controlled double-blind clinical trial.
AB  - OBJECTIVE: To examine the effects of pulsed short-wave diathermy (PSWD),
      delivered at an intensity sufficient to induce a thermal sensation and at an
      athermal intensity, in comparison with a placebo short-wave diathermy treatment,
      on reported pain, stiffness and functional ability and on mobility performance of
      patients with osteoarthritis of the knee. DESIGN: A placebo-controlled double
      blind trial with sequential allocation of patients to different treatment groups.
      SETTING: Outpatient physiotherapy department. SUBJECTS: One hundred and three
      consecutive patients, mean age 73.7 (+/-6.6) years with osteoarthritis of one or
      both knees for at least three months. INTERVENTIONS: All participants received
      three 20-min-long treatments per week for three weeks. One group received PSWD
      with mean power of 18 W (thermal effect), one group received PSWD with mean power
      of 1.8 W (athermal effect), and one group received sham short-wave diathermy
      treatment. Patients were assessed before the initial treatment, immediately
      following the last treatment, and at a three-month follow-up. MAIN MEASURES:
      Outcome measures included the WOMAC Osteoarthritis Index, which assessed reported
      pain, stiffness, and functional ability, and four measures of mobility
      performance: Timed Get Up and Go test (TGUG), stair-climbing, stair, descending
      and a 3-min walk. RESULTS: A difference across time was observed for the pain and
      stiffness categories of the WOMAC Osteoarthritis Index (p = 0.033 and p = 0.008,
      respectively), with no differences between groups. No other significant
      differences across time or between groups were observed in any of the other
      measures. CONCLUSION: The findings do not demonstrate pulsed short-wave
      diathermy, as it is utilized in clinical settings, to be effective in the
      treatment of osteoarthritis of the knee.

PMID- 15859527
TI  - Gait outcomes after additional backward walking training in patients with stroke:
      a randomized controlled trial.
AB  - OBJECTIVE: To examine the effectiveness of additional backward walking training
      on gait outcome of patients post stroke. DESIGN: Randomized controlled trial.
      SETTING: Medical centre. SUBJECTS: Twenty-five subjects with stroke, who were
      lower extremity Brunnstrom motor recovery stage at 3 or 4 and were able to walk
      11 m with or without a walking aid or orthosis, randomly allocated to two groups,
      control (n = 12) and experimental (n = 13). INTERVENTIONS: Subjects in both
      groups participated in 40 min of conventional training programme three times a
      week for three weeks. Subjects in experimental group received additional 30 min
      of backward walking training for three weeks at a frequency of three times per
      week. MAIN MEASURES: Gait was measured using the Stride Analyzer. Gait parameters
      of interest were walking speed, cadence, stride length, gait cycle and symmetry
      index. Measures were made at baseline before commencement of training (pre
      training) and at the end of the three-week training period (post-training).
      RESULTS: After a three-week training period, subjects in experimental group
      showed more improvement than those in control group for walking speed (change
      score: 8.60 +/- 6.95 versus 3.65 +/- 2.92, p-value = 0.032), stride length
      (change score: 0.090 +/- 0.076 versus -0.0064 +/- 0.078, p-value = 0.006), and
      symmetry index (change score: 44.07 +/- 53.29 versus 5.30 +/- 13.91, p-value =
      0.018). CONCLUSIONS: This study demonstrated that asymmetric gait pattern in
      patients post stroke could be improved from receiving additional backward walking
      therapy.

PMID- 15859528
TI  - The effect of botulinum toxin type A treatment of the lower extremity on the
      level of functional abilities in children with cerebral palsy: evaluation with
      goal attainment scaling.
AB  - OBJECTIVE: To measure the effect of botulinum toxin type A (BTX-A) treatment in
      children with cerebral palsy with regard to individual goals concerning
      functional abilities, using goal attainment scaling. DESIGN: A single-blind
      randomized multiple baseline/treatment phase design across subjects. SETTING: The
      paediatric department of a rehabilitation centre. SUBJECTS: Eleven children with
      cerebral palsy participated. INTERVENTION: BTX-A treatment of the lower
      extremity. MAIN MEASURES: A six-point goal attainment scaling of three individual
      treatment goals at the level of functional abilities. Standardized video-tapes of
      each goal were recorded weekly for a period of 14 weeks. Rating on the
      predetermined goal attainment scaling was blinded. RESULTS: Nine of the 11
      subjects showed significant improvement in 18 out of 33 goals. Seven subjects
      showed clinically relevant improvement (at least 2 points on the goal attainment
      scaling) in 11 goals. Testing the difference between all medians of baseline
      measurements (after correction for improvement during baseline) and the medians
      of the treatment phase measurements for all goal attainment scaling scores (n =
      33) resulted in significant improvement (p < 0.001). Tested at subject level
      (medians of the three goal attainment scaling scores per assessment, n = 11), a
      significant improvement was also found (p = 0.005). The change in goal attainment
      scaling score was related to the moment of treatment with BTX-A. CONCLUSION:
      Clinically relevant improvement in individual rehabilitation goals at ability
      level, achieved with the treatment of BTX-A in children with cerebral palsy, were
      demonstrated using the goal attainment scaling method.

PMID- 15859529
TI  - The effects of progressive resistance training for children with cerebral palsy.
AB  - OBJECTIVES: To investigate the effects of progressive resistance training of
      quadriceps and hamstrings muscles in children with cerebral palsy (CP). DESIGN:
      Pilot study using a repeated measures design with measurements at baseline,
      immediately after six weeks training then at four-week follow-up. SETTING: The
      project was undertaken within the physiotherapy department of two special schools
      in Glasgow. SUBJECTS: A convenience sample of eight children aged between six and
      12 years, with hypertonic CP. INTERVENTION: The subjects participated three times
      per week in a six-week, progressive, free-weight, strengthening programme.
      OUTCOME MEASURES: Maximum isometric muscle strength and resistance to passive
      stretch were measured with a hand-held myometer. The Gross Motor Function Measure
      and a 10-metre timed walking test, were used to assess function and gait
      parameters respectively. RESULTS: Muscle strength increased, with the quadriceps
      to hamstrings strength ratio moving towards normal. These changes were retained
      at follow-up. Muscle tone decreased and continued to decrease to follow-up. The
      standing (D) and walking, running and jumping (E) goal areas of the Gross Motor
      Function Measure showed improvement that continued towards follow-up. Walking
      speed and step rate increased. CONCLUSIONS: A future large-scale randomized
      controlled study would be of value to substantiate these results as the small
      convenience sample and lack of control group limit this study. However, the
      finding that no adverse effect accompanied the positive outcomes in strength and
      function may encourage clinicians to consider resistance training alongside
      standard therapeutic interventions.

PMID- 15859530
TI  - Assessment of readiness to change in patients with osteoarthritis. development
      and application of a new questionnaire.
AB  - OBJECTIVE: To develop a self-report measure for assessment of the stage of change
      in patients with osteoarthritis, in order to identify patients who would benefit
      from a self-management programme. METHODS: According to the 'stages of change'
      model a questionnaire was developed with three groups of items corresponding to
      the precontemplation stage (Pre), the contemplation (Cont) and the action (Act)
      stage. Internal consistency and factor structure of this questionnaire were
      investigated by assessing Cronbach's alphas and by performing factor analysis.
      SUBJECTS AND SETTING: The questionnaire was offered to 273 patients who entered a
      randomized clinical trial on self-management in a general health care setting.
      RESULTS: Factor analysis revealed that most items corresponded to the a priori
      described groups, while some items were not loading on the presumed factor. In
      each subgroup some items were deleted, resulting in a 15-item questionnaire.
      After this item reduction Cronbach's alphas were 0.72 (Pre), 0.76 (Cont) and 0.79
      (Act) and all factor loadings were satisfactory (above 0.35). Classification
      revealed some differences between parts of the total group, for example in the
      proportion of patients in the preparation stage (recruited by general
      practitioner = 33.6%; advertisement = 49.2%). CONCLUSIONS: The Stages of Change
      Questionnaire in Osteoarthritis, a 15-item questionnaire to assess the 'stage of
      change' of a patient with osteoarthritis showed good internal consistency and
      adequate factor structure. These findings warrant further studies on validity and
      applicability in a clinical context.

PMID- 15859531
TI  - Translation, adaptation and validation of the Shoulder Rating Questionnaire (SRQ)
      into the Dutch language.
AB  - OBJECTIVE: To translate and adapt the original English version of the Shoulder
      Rating Questionnaire (SRQ) into the Dutch language (SRQ-DLV) and evaluate its
      internal consistency, reliability, validity and responsiveness to clinical
      changes. DESIGN: Prospective study. SETTING: Outpatient departments of
      orthopaedics, radiology and physical therapy of an academic and a non-academic
      hospital. SUBJECTS: One hundred and seven patients treated for unilateral
      shoulder disorder (adhesive capsulitis 68, calcifying tendinitis 22, impingement
      syndrome or rotator cuff tear 17). METHODS: The original SRQ was translated and
      adapted following international guidelines. The SRQ-DLV was used among other
      measures of body function and structure, activities and societal participation in
      order to determine reliability, internal consistency, validity and
      responsiveness. Assessments were done at baseline and three months after
      treatment, with the SRQ-DLV being re-administered within one week before the
      baseline measurement and the start of the treatment for testing reliability.
      RESULTS: Cronbach's alpha for internal consistency was 0.89 for the total
      questionnaire and 0.81, 0.80, 0.72 and 0.84 for the domains pain, daily
      activities, sports/recreational activities and work, respectively. Test-retest
      reliability of the SRQ-DLV and its subscales ranged from 0.63 to 0.86. The
      summary score of the SRQ-DLV correlated with measures of shoulder function, daily
      activities and quality of life. Except for the work subscale of the SRQ-DLV,
      large effect sizes, reflecting its responsiveness to clinical changes after
      treatment, were found for both the summary and the subscales scores. CONCLUSIONS:
      Empirical data support that the SRQ-DLV is a reliable, valid and responsive
      measure to be used in clinical trials including Dutch patients with various
      shoulder disorders.

PMID- 15859532
TI  - A prospective study on paediatric traffic injuries: health-related quality of
      life and post-traumatic stress.
AB  - OBJECTIVES: To examine children's reports of their health-related quality of life
      (HRQoL) following paediatric traffic injury, to explore child and parental post
      traumatic stress, and to identify children and parents with adverse outcomes.
      DESIGN: Prospective cohort study. ASSESSMENTS: shortly after the injury, three
      months and six months post injury. SETTING: Department of Traumatology,
      University Hospital. SUBJECTS: Fifty-one young traffic injury victims aged 8-15
      years. MAIN MEASURES: TNO-AZL Children's Quality of Life questionnaire and the
      Impact of Event Scale. RESULTS: Short-term adverse changes in the child's HRQoL
      were observed for the child's motor functioning and autonomy. At three months,
      12% of the children and 16% of the parents reported serious post-traumatic stress
      symptoms. Increased stress at three months, or across follow-up, was observed
      among hospitalized children, children with head injuries, and children injured in
      a motor vehicle accident. Parental stress was related to low socioeconomic status
      and the seriousness of the child's injury and accident (hospitalization, head
      injury, serious injury, motor vehicle involved, others injured). CONCLUSIONS: The
      children reported only temporary effects in their motor functioning and autonomy.
      Post-traumatic stress symptoms following paediatric traffic injury were not only
      experienced by the children, but also by their parents.

PMID- 15859533
TI  - Psychological services for people with stroke: compliance with the U.K. National
      Clinical Guidelines.
AB  - BACKGROUND: The UK National Clinical Guidelines for Stroke (2000) include
      recommendations on psychological services. The third National Sentinel Audit of
      Stroke was completed in 2001-2002. OBJECTIVES: To examine the extent to which UK
      stroke services complied with the national guidelines. DESIGN: Use of three
      retrospective case note audits of hospital admissions, covering the period from
      admission to six months after discharge, and audits of how stroke services were
      organized. SETTING: Hospitals within England, Wales, Northern Ireland, the
      Channel Islands and the Isle of Man. SUBJECTS: Stroke patients admitted
      consecutively within a three-month time frame. MAIN MEASURES: Compliance with the
      guidelines on mood disorders and cognitive impairments, and changes between
      audits. RESULTS: The 2001-2002 audit provided data on 60% of possible
      participants, from 145 hospitals and 5152 patients. Compliance with the guideline
      to screen for mood disturbance was poor; the median patient compliance rate of
      hospitals was 50%. More hospitals (88%) had a locally agreed cognitive assessment
      protocol in 2001-2002 than in 1998 (68%) and in 1999 (82%). However, actual rates
      of screening for cognitive difficulties were lower than implied by the existence
      of a local protocol. There were no strong case-mix associates of mood and
      cognitive screening. Access to clinical psychologists was poor. Mood and
      cognitive assessment rates were not much better for stroke units with access to
      clinical psychologists than for units without access (mood: p = 0.6, cognition: p
      = 0.09). CONCLUSIONS: Although compliance with some of the guidelines has
      improved, many areas in current psychological services for stroke urgently need
      attention.

PMID- 15859534
TI  - Outdoor activity and performance status as predictors of survival in hypoxaemic
      chronic obstructive pulmonary disease (COPD).
AB  - BACKGROUND: Performance status has been associated with survival in hypoxaemic
      chronic obstructive pulmonary disease (COPD) patients on long-term oxygen
      therapy. OBJECTIVE: To determine whether self-reported outdoor activity and
      performance status are independent predictors of survival in hypoxaemic COPD
      patients on long-term oxygen therapy. DESIGN, SUBJECTS AND MAIN MEASURE: In a
      prospective design, survival over an eight-year period was studied in 226 Danish
      patients on long-term oxygen therapy. They were subdivided according to self
      reported mobility (+/-outdoor activity) and World Health Organization (WHO)
      performance status (score 0-4). RESULTS: A total of 148 patients (65.5%) reported
      outdoor activity. Compared to the immobile patients, those reporting outdoor
      activity had higher performance status, higher body mass index and lower duration
      of oxygen administration. In multivariate analyses adjusting for body mass index,
      gender and age, both poor performance status and lack of outdoor activity were
      associated with poor survival (p-levels 0.006 and 0.045, respectively). Lack of
      outdoor activity was associated with increased mortality (relative risk (RR) and
      95% confidence interval of dying was 1.39 (1.01-1.91)) and significantly higher
      risk was found among those with age in the youngest tertile (less than 66.4
      years), the relative risk of dying was 2.18 (1.20-3.95). CONCLUSIONS: This study
      shows that self-reported performance status and outdoor activity are independent
      predictors of survival in hypoxaemic COPD patients on long-term oxygen therapy.
      However, our study suggests that in the most elderly patients, outdoor activity
      does not predicting survival. Further studies are needed to determine whether
      interventions that facilitate outdoor activity (e.g., pulmonary rehabilitation)
      have an effect on survival in this group of patients.

PMID- 15859535
TI  - Gait and calf muscle endurance in patients with chronic venous insufficiency.
AB  - OBJECTIVE: To gain insight in gait and calf muscle endurance in patients with
      severe chronic venous insufficiency. METHODS: Fifteen patients with severe
      chronic venous insufficiency (healed or active ulcers) and 19 healthy controls
      were selected for this study. Subjects had to perform eight trials at preferred
      walking speed and eight trials at instructed walking speed (1.25 m/s) during
      which the gait parameters were recorded. The calf muscle endurance was tested by
      use of the heel-rise test. RESULTS: Patients had a significantly lower preferred
      walking speed (1.25 m/s +/- 0.31) compared with healthy controls (1.44 m/s +/-
      0.0.15) (p = 0.039). During preferred walking speed patients had a wider base of
      support (p = 0.003), a bigger step time (p = 0.005), and a bigger stride time (p
      = 0.004) compared with healthy controls. At instructed walking speed only base of
      support was different between the two groups (p = 0.016). Patients had a
      significantly (p = 0.003) smaller number of heel rises (14.6 +/- 7.34),
      indicating decreased calf muscle endurance compared with controls (23.5 +/-
      6.54). CONCLUSION: This study indicates a disturbed gait and decreased calf
      muscle endurance in patients with severe chronic venous insufficiency. The
      results of this study point to a possible role for gait and strength training in
      the rehabilitation process of patients with severe chronic venous insufficiency.

PMID- 15859536
TI  - Definition of a randomized controlled trial.

PMID- 15859537
TI  - [Could progeria be a model for the natural process of aging?].
AB  - Acceleration of ageing of urban populations causes the urgent need to carry out
      research in this area. One of the proposed models of investigation may be
      progeria. The most frequent syndromes of progeria and the way they are inherited
      were described. Molecular mechanisms which have essential influence on premature
      ageing in progeria were discussed. Moreover, their analogies with natural
      biological process were presented.

PMID- 15859538
TI  - [Platelets and platelet microparticles glycoprotein IIb/IIIa complex in patients
      with unstable angina].
AB  - Platelet activation is known to play a key role in pathogenesis of acute coronary
      syndrome (ACS). Platelet activation leads to increased numbers of glycoprotein
      (GP) IIb/IIIa complex on the platelet membrane. On the other side antiplatelet
      therapy in patient with unstable angina can suppress the actions of platelet. THE
      AIM: To estimate by flow cytometry GP IIb/IIIa expression on the platelets and
      platelet microparticles membrane. MATERIAL AND METHODS: The study involved 21
      patients with unstable angina, before (group B1) and after treatment (group B2).
      All subjects received aspirin, heparin (Clexane) and b-blocker. The control group
      consisted of 24 healthy subjects. RESULTS: Patients with unstable angina in group
      B1 were by 12% higher expression of GP IIb/IIIa than control group (62.6 vs
      55.1%). In group B2- before treatment- the percentage of platelet expressing GP
      IIb/IIIa was lower (60.1%) than in the group B1. In both groups, B1 and B2,
      percentage of platelet microparticles expressions GP IIb/IIIa was elevated 8.5%
      and it was significantly higher than in the control group (5.3%). CONCLUSIONS:
      Our study show that patients with unstable angina had a higher expression GP
      IIb/IIIa on the platelets membrane and elevated percentage of platelet
      microparticles confirm platelet activation. There was no significantly different
      in platelet GP IIb/IIIa expression after the antiplatelet therapy in patients
      with unstable angina.

PMID- 15859539
TI  - [Platelet activation in unstable angina depending on troponin I concentration].
AB  - Platelet activation as a result of atheromatous plaque rupture in ischaemic heart
      disease can be detected by assesses plasma concentration of beta-thromboglobulin
      (beta-TG) and indirectly by changes in platelet counts (PLT). At the same time
      myocardial ischaemia and local destruction of cardiomyocyte leads to the increase
      troponin I concentration. The aim of this study was an evaluation of correlation
      between markers of platelet activation in vivo (beta-TG and PLT) and the level of
      troponin I in patients with unstable angina. MATERIAL AND METHODS: In our study
      54 patients were divided into three groups depending on the risk of myocardial
      infarction. The first group - 10 patients, moderate risk of infarction, troponin
      I plasma concentration below 0.1 ng/ml, the second group - 33 patients, high risk
      of infarction, troponin I level between 0.2-1.5 ng/ml, and the third group - 11
      patients with myocardial infarction, troponin I level above 1.5 ng/ml. The
      control group - 26 healthy subjects free from cardiovascular diseases. RESULTS:
      In the present study we found a significant increase (p < 0.05) in the beta-TG
      concentration in group two (18.2 IU/microl) and group three (17.4 IU/microl)
      compared with control (10.9 IU/microl). The PLT was a significantly lower only in
      group two (181.2 x 10(3)/microl) compared with the control group (217.3 x
      10(3)/microl). CONCLUSIONS: We found that the plasma concentration of beta-TG as
      a marker of platelet activation increase depends on higher risk of myocardial
      infarction measured by troponin I plasma concentration. beta-TG may be also
      useful parameter to help estimate the risk of myocardial infarction.

PMID- 15859540
TI  - [Arterial hypertension in children with end-stage renal failure treated with
      hemodialysis].
AB  - Cardiovascular disorders contribute in increased morbidity and mortality of
      patients with chronic renal failure. Uncontrolled, long-term arterial
      hypertension is noted as a major risk factor. The study aimed at evaluation of
      arterial hypertension incidence and efficiency of its treatment among patients on
      maintenance hemodialysis (HD). MATERIAL AND METHODS: The study included 24
      children and young adults with chronic renal failure on hemodialysis treatment,
      for the period longer than 6 months, in the 1997-2002 years. Patients data were
      retrospectively analyzed in 3-month's intervals. At the beginning of follow-up
      systolic and diastolic arterial hypertension (values exceeding 95 percentile
      value for age and height) before dialysis session was revealed respectively in
      58% and 46% of children, and after dialysis session the occurrence of both
      systolic and diastolic hypertension was 42%. RESULTS: After 33 months of
      treatment the incidence of predialysis systolic and diastolic hypertension was
      respectively 15.5% and 8% and postdialysis both systolic and diastolic
      hypertension - 23%. Ejection fraction (EF) increased almost significantly after
      18 months of treatment with hemodialysis, but after 30 months EF reached baseline
      value. Cardiac contractility was nonsignificantly improved after 18 months of
      treatment, and after 30 months declined to baseline value. 62.5% of children in
      examined group were treated with more than one antihypertensive drug.
      CONCLUSIONS: We found that the amount of antihypertensive drugs correlated with
      values of systolic and diastolic blood pressure till 18 month of follow-up as
      well as in 30 month of observation.

PMID- 15859541
TI  - [Treatment of chronic hepatitis with interferon in children with kidney
      diseases].
AB  - The study aimed at evaluation of chronic hepatitis treatment results in children
      previously treated from nephrological indications in 1994-2002 years. MATERIAL
      AND METHODS: Examination was performed in 42 children in the age 10.2 +/- 4.8
      years at the onset time of interferon (INF) treatment application. In 30 children
      (71.4%) chronic HBV infection, in 8 (19.1%) - HCV infection, in 4 (9.5%) - mixed
      HBV and HCV infection in phase of replication was revealed. Among examined
      children in 26 (61.9%) symptoms of glomerulonephritis were previously reported,
      in 17 (40.5%) - symptoms of nephrotic syndrome; in 9 (21.4%) - chronic renal
      failure was observed. 22 children received prednisone treatment. Concentrations
      of albumin, gamma- globulin, bilirubin, haemoglobin, creatinine, haematocrit,
      leukocytosis, activity of alanine aminotransferase (ALT), chronic hepatitis
      markers, before, during and 6 and 12 months after treatment termination were
      evaluated. IFN alpha-2a, alpha-2b and human recombined IFN-alpha were applied
      RESULTS: In 22 (52.4%) children ALT values before treatment not exceeded 100
      IU/l. Liver biopsy was performed in 39 children. In 18 (46.2%) - high activity of
      inflammatory process was revealed; only in 5 of them with ALT activity above 100
      IU/l. Higher leukocytosis at the beginning of treatment was accompanied by
      diminished activity of inflammatory process. In 14/34 children seroconversion was
      obtained in HBe markers, in 4/12 HCV-RNA elimination occurred after the 1st
      course of IFN. Only in 5 (11.9%) children treatment was stopped because of side
      effects (not connected with urinary tract), in 1 - because of relapse of main
      disease. 2nd course was applied in 13 children. In 2 - seroconversion in HBe
      markers was obtained. CONCLUSIONS: Considering the small number of examined
      children full evaluation of chronic hepatitis treatment efficacy is not possible.
      It seems comparable as observed in population of children without the risk of
      nephropathies. IFN treatment in children on previous medication of kidney
      disease, in most cases does not create complications leading to earlier drug
      cessation. In the case of glomerulonephritis also does not bear an increased risk
      of relapse of main disease.

PMID- 15859542
TI  - [The total antioxidant capacity and low-molecular antioxidant concentration in
      plasma of type-2 diabetes patients with different stage of metabolic compensation
      and concomitant diabetic nephropathy].
AB  - The experimental and clinical researches suggest important role of advanced
      glycation end products (AGE) and oxidative stress in pathogenesis of diabetic
      angiopathy also including nephropathy. It is especially pointed at by the
      research done on inadequately controlled long-term diabetes. The aim of the study
      was to asses the total antioxidant capacity of plasma as well as the
      concentration of low-molecular antioxidants in plasma in diabetes type 2 patients
      in different stage of metabolic compensation and concomitant diabetic
      nephropathy. MATERIAL AND METHODS: 91 diabetes type 2 patients took part in the
      research (31 patients with metabolic compensated diabetes, 14 patients with
      metabolically decompensated diabetes, 14 patients with incipient and 16 patients
      with overt nephropathy). The control group consisted of 40 healthy men. The total
      antioxidant capacity was fluorometrically marked by means of ficoerythryne. The
      concentration of low-molecular antioxidants in plasma was marked on the basis of
      the time of free radicals scavenging by means of Trolox (6-hydroxy-2, 5,7, 8
      tetramethethylchroman-2-carboxylic acid) of known concentration. RESULTS: In
      patients with diabetes type 2 the total biggest antioxidant capacity was noted in
      metabolically compensated diabetes group and the total lowest antioxidant
      capacity was noted in diabetic patients with overt nephropathy. The highest mean
      concentration of low-molecular antioxidants was noted in metabolically
      compensated diabetes group and the lowest in diabetic patients with overt
      nephropathy. These differences were statistically significant. CONCLUSION: In
      patients with diabetic nephropathy with the development of the disease
      significant insufficiency of plasma antioxidant barrier is noted. Diminishing of
      the total antioxidant capacity and depletion of plasma antioxidants noted in
      diabetes type 2 patients, especially inadequately metabolically controlled may
      constitute the essential pathogenetic factor of vascular complication in
      diabetes.

PMID- 15859543
TI  - [Serum IL-2 and sIL-2R concentration in children with chronic hepatitis B].
AB  - The aim of the study was evaluation of serum IL-2 and sIL-2R concentration in
      children with chronic hepatitis B without previous treatment. MATERIAL AND
      METHODS: Investigations were performed on sera from 27 children, 13 HBsAg and
      HBeAg positive (group I) and 14 HBsAg positive, HBeAg negative, anti-HBe positive
      (group II). Serum IL-2 and sIL-2R concentrations were detected with ELISA method.
      RESULTS: In all examined children serum IL-2 concentrations were decreased. The
      mean values of sIL-2R in group I was 4,40 (from 1,78 to 15,74) and in group II
      was 2,60 ( from 1,59 to 4,81) ng/ ml and were statistically significant higher in
      HBeAg positive children (group I, p < 0.005). The mean ALT activity in this group
      of children was increased (mean 74 U/I) . The positive correlation between sIL-2R
      and ALT activity was observed in group I. CONCLUSIONS: In children with chronic
      hepatitis B a deficiency of Th1 mediated immunological response was observed.
      HBeAg/anti-HBe seroconversion seems to change the IL-2/sIL-2R balance.

PMID- 15859544
TI  - [Assessment of arterial compliance and elasticity during graded head-up tilt in
      healthy people].
AB  - Head-up tilting causes many changes in cardiovascular system (CVS), and
      stimulates sympathetic nervous system, which leads to increase of total
      peripheral resistance (TPR) and acceleration of heart rate (HR). The hemodynamic
      changes influence pulse wave shape and mechanical properties of the arterial
      system. Arterial compliance (C) and elastance (Ea) are parameters used to
      describe mechanical properties of the arterial system. The study aim was to
      evaluate arterial stiffness by evaluation of arterial elastance and compliance
      during graded head-up tilting and assessment of the relationship between the
      change of the tilt angle and those parameters in healthy young subjects. MATERIAL
      AND METHODS: The study was conducted in 32 healthy volunteers (21-30 years old,
      17 female). After 20 minutes of supine rest, the head-up tilting was performed
      with the use of a tilt-table with electrical engine. The tilt-table was stopped
      for 1 minute after reaching the angle of 15 degrees and its multiples (i.e. 30,
      45, 60, 75 and 90 degrees). Hemodynamic parameters were measured by means of
      chest bioelectrical impedance method (BioZcom monitor, CardioDynamics, USA). The
      association of the sine of the tilt angle with Ea and C was calculated with the
      use of Pearson correlation. RESULTS: A strong positive correlation between the
      sine of the tilt angle and Ea was noted (r = 0. 5084; p < 0.0001). A negative
      correlation between the change of the tilt angle during head-up tilting and C was
      found (r = -0.4608; p < 0.0001). CONCLUSION: During graded head-up tilting,
      arterial stiffness increases in young healthy people.

PMID- 15859545
TI  - [Thymectomy in myasthenia gravis].
AB  - OBJECTIVES AND METHODS: To evaluate the results of thymectomy in myasthenia
      gravis we performed retrospective analysis of 82 consecutive patients in the mean
      age of 39 +/- 15 treated between 1991 and 2001. All patients underwent extended
      thymectomy by median sternotomy. Follow-up was assessed in 74 of 81(91.4%)
      patients, in the mean age of 39 +/- 15, discharged from the Department. RESULTS:
      Fifty three (71.6%) patients had symptoms of myasthenia gravis for less than 2
      years. According to Osserman's classification 8 (10.8%) patients were assessed as
      class I, 32 (43.2%) as IIA 26 (35.2%) as IIB and 8 (10.8%) as IIC. In the
      postoperative period 8 (10.8%) patients had respiratory insufficiency, 5 (6.8%)
      were reoperated for bleeding. One patient died (1.4%) due to bilateral pneumonia
      and pulmonary insufficiency. After thymectomy the improvement of patient's
      clinical status was observed in 46 patients (86.4%) and complete remission was in
      13 patients (17.6%). Prompt improvement after thymectomy (p = 0.008) and short
      duration of symptoms (p = 0.036) are positive predictive factors. Patients in
      class I had significantly better prognosis concerning complete remission (p =
      0.036). Age, gender, histology of the thymus, and type of the thymoma had no
      influence on long time follow up. CONCLUSIONS: Extended thymectomy is a safe
      procedure leading to the improvement in majority of patients treated for
      myasthenia gravis.

PMID- 15859546
TI  - [Assessment of the release of thyroid hormones in septic shock--prognostic
      significance].
AB  - Septic shock is the reason of human body organs dysfunctions including the
      hormonal system. There are abnormal thyroid hormones releasing as well. It is
      also noticed that sepsis caused serious disturbances in pituitary-thyroid axis
      functions. This is called euthyroid sick syndrom - (ESS). THE AIM: To qualify the
      prognostic value of thyroid hormones serum levels changes in patients with septic
      shock. MATERIAL AND METHODS: 20 patients with septic shock were included into
      study. Septic shock was diagnosed according to AACP/SCCM criteria. The study
      group was divided into two subgroups: survivors (n = 10) and nonsurvivors (n =
      10). 20 healthy volunteers were the control group. Blood for analysis was taken
      at the moment of septic shock recognition and on the 1st, 2nd, 5th and 10th day
      of the observation between 8 a.m. and 9 a.m. We studied thyrotropin (TSH), free
      triiodothyronine fraction (fT3) and free thyroxin fraction (fT4) serum levels,
      APACHE II and APACHE III score, acute lung injury (ALI) or acute respiratory
      distress syndrome (ARDS). RESULTS: During our study we noticed significant
      decrease of fT3 and TSH serum levels (respectively 2.36 +/- 0.79 pg/ml and 0.76
      +/- 1.12mU/I) according to the control group (respectively 3.28 +/- 0.61 pg/ml
      and 0.95 +/- 0.46mU/l). Nonsurvivors had significantly lower TSH serum level
      (0.37 +/- 0.62 mU/I) in comparison to survivors (1.27 +/- 1.45 mU/I) in spite of
      very similar fT3 serum level (respectively 2.45 +/- 0.87 pg/ml and 2.22 +/- 0.66
      pg/ml). It could mean that there were disturbances in the pituitary-thyroid axis
      function in patients who did not survive. Our study did not show any correlations
      between thyroid hormones serum levels and APACHE II score, APACHE III score, ALI
      or ARDS. CONCLUSIONS: This study show that low TSH serum level could be a
      significant prognostic factor of death in patient with septic shock especially
      with low fT3 serum level. The results also suggest that ESS could be a
      consequence of pituitary TSH releasing disturbances.

PMID- 15859547
TI  - [Clinical picture of celiac disease in children].
AB  - During the last few years we have been observing the decreasing incidence of the
      symptomatic celiac disease and increasing incidence of mono- and asymptomatic
      disease. Various atypical symptoms and extraintestinal manifestations were
      observed in older children (above 7 years) and in adults. Clinical symptoms of
      celiac disease may appear at any age, in each of the following forms: clinical
      celiac disease (symptomatic), silent (oligosymptomatic) or latent, with late
      manifestation, being the effect of stress, pregnancy, infections or excessive
      dietary gluten provocation. THE AIM OF THE STUDY: The presentation the variety of
      clinical pictures of celiac disease in children. MATERIALS AND METHODS: We have
      evaluated the clinical course of celiac disease in 16 children (13 girls and 3
      boys), aged between 12 months to 17 years (mean-7,5 years). The celiac disease
      was diagnosed on the grounds of clinical symptoms, histopathological examination
      of the small intestinal endoscopic biopsy and immunological examinations: serum
      antitransglutaminase antibodies and anti-endomysium antibodies. RESULTS: Most
      commonly diagnosed form was the silent, monosymptomatic celiac disease. Four
      children manifested with growth retardation, one with osteoporosis, and one with
      iron deficiency anemia resistant to treatment. Two girls (aged 16 and 17 years)
      presented with symptomatic celiac disease. In 3 patients despite the
      gastrointestinal symptoms and histopathological changes present (villous atrophy,
      Marsh's index > 40) we did not find any immunological markers of celiac disease
      (with normal IgA levels). CONCLUSIONS: School-aged children with celiac disease,
      in many cases have no evident clinical and functional disorders caused by gluten
      intake, despite to presence of considerable abnormalities in the
      histopathological examination.

PMID- 15859548
TI  - [Electrogastrography in children with functional abdominal pain and gastritis].
AB  - Electrogastrography (EGG) is non-invasive method for diagnosis of gastric
      electrical activity. THE AIM OF STUDY: We analysed gastric activity in children
      with chronic abdominal pain and functional disorders of alimentary tract or
      gastritis. MATERIAL AND METHODS: Skin EGG with 30-minutes recordings in
      preprandial period and after standard meal were done in 155 children, mean age
      11,6 +/- 3,6 years. We analyzed data in groups: 1-functional abdominal pain
      (FAP), 2-gastritis, Helicobacter pylori negative, 3-gastritis, Helicobacter
      pylori positive, 4-controls. RESULTS: EGG was in normal range in 32% of patients
      with FAP and in 27% of patients with gastritis. Abnormalities in gastric rhythm
      were noticed in highest percent in gr. 2 in fasting state. Normogastry was
      dominant in postprandial period in all groups. Statistical differences of some
      parameters of EGG (dominant frequency, dominant power) were found among study
      groups. We found higher percent of bradygastry in fasting state compared with
      postprandial period. CONCLUSIONS: We conclude that different abnormalities in
      gastric myoelectrical activity could exist in chronic abdominal pain; dominant
      preprandial rhythm is mainly affected. We couldn't find typical changes in
      electrogastrogram for differentiate FAP and gastritis.

PMID- 15859549
TI  - [Antioxidant status of patients with primary colorectal cancer and liver
      metastases of colorectal cancer].
AB  - In the present work we examined selected parameters of antioxidant status in
      patients with primary colorectal cancer and liver metastasis of colorectal
      cancer. Total antioxidant status (TAS), activity of superoxide dismutase (SOD)
      and catalase (CAT) were examined in colorectal primary cancer, liver metastasis
      of colorectal cancer and in blood serum of patients before and after surgery. It
      was found that patients have disordered function of the the antioxidant system.
      This is demonstrated by decreased TAS and changes in the activity of SOD and CAT,
      both in tumor tissue and blood serum.

PMID- 15859550
TI  - [Expression of L-selectin on the surface of neutrophils stimulated by TNF-alpha
      and level of sL-selectin in serum of patients with lung cancer].
AB  - The aim of the study was to estimate L-selectin expression on peripheral blood
      PMN stimulated by TNF-alpha and concentration of a soluble form of L-selectin in
      serum of patients with small cell and non-small cell lung cancer. The results
      showed an increased expression of L-selectin on PMN isolated from peripheral
      blood and an elevated concentration of sL-selectin in serum of patients with
      small cell and non-small cell lung cancer. An increased expression of these
      adhesion molecules may be the result of neutrophil activation by inflammatory
      cytokines.

PMID- 15859551
TI  - [Seasonal changes in bronchial reactivity in pollinosis patients].
AB  - THE AIM OF THE STUDY: To evaluate seasonal changes in bronchial hyperreactivity
      (BHR) in patients suffering from pollinosis, sensitive to Ryegrass engl. MATERIAL
      AND METHODS: The studies were carried out on 26 patients and 20 healthy subjects.
      All the patients had a history of seasonal allergic rhinitis. The following
      measurements were performed outside and during the pollen season: bronchial
      provocation test (BPT) with metacholine and 4.5% NaCl, serum concentration of
      specific and total IgE. RESULTS: Outside the pollen season additionally the BPT
      with Ryegrass engl. allergen was performed and 88% of the pollinosis patients had
      positive result of the test. After 4.5% NaCl bronchial challenge positive results
      had 2 out of 26 patients outside the season, and 3 during the season. Bronchial
      hyperreactivity to metacholine (PC20 < 8 mg/ml) were observed in 4/26 (15.4%)
      persons outside the season and in 7 (26.9) during the season. The healthy
      subjects had no bronchoconstriction neither after metacholine or 4.5% NaCl.
      During the pollen season the increase in serum concentration of tIgE and sIgE was
      observed only in pollinosis patient. CONCLUSIONS: There was not found a
      correlation between BHR to the allergen and serum total IgE nor specific IgE
      concentration.

PMID- 15859552
TI  - [Risks factors for the development of diabetes in women with history of
      gestational diabetes mellitus].
AB  - Women who suffered from impaired carbohydrate metabolism during pregnancy are
      more likely to develop different types of diabetes later in their lives. The aim
      of this paper was to study the risk factors for the development of diabetes in
      group of women with gestational diabetes mellitus (GDM) in anamnesis. MATERIALS
      AND METHODS: 200 women took part in this study, who had gestational diabetes
      diagnosed between 1980-1998. All women were divided into 4 groups depending on
      the type of disorders occurring at the moment of examination: DM1 - women
      diagnosed with type I diabetes, DM2 - women diagnosed with type 2 diabetes, IGT
      women with glucose levels in OGTT, which applied to impaired glucose tolerance
      (acc. to WHO criteria), NDM - women with no clinical signs of diabetes, with
      normal result of OGTT. RESULTS: The risk of diabetes development is significantly
      higher (independently of the clinical type) in women who had had GDM include:
      high glucose levels at the time of GDM diagnosis, early onset of symptoms -
      related to weeks of gestation, and the insulin treatment during pregnancy.
      However multifactor analysis indicates that the only significant risk factors for
      DM 1 are early onset of diabetes during pregnancy and high glucose levels 2 hours
      after OGTT during pregnancy (p < 0.05). High levels of glucose 2 hours after OGTT
      and high Body Mass Index (BMI) turned out to be the independent risk factors of
      diabetes type 2 (p < 0.05). CONCLUSIONS: Knowledge of risk factors allows to
      recognize a diabetes high risk group among women who suffered from diabetes
      during pregnancy.

PMID- 15859553
TI  - [Analysis of risk factors for ectopic pregnancy in own material in the years 1993
      2002].
AB  - The ectopic pregnancy is still a life-threatening condition. The risk factors for
      ectopic pregnancy are divided into four groups: 1) mechanic factors, 2) tubal
      dysfunction, 3) assisted reproductive techniques (ART) and 4) hormonal factors.
      MATERIAL AND METHODS: On basis of the analysis of medical documentation we
      determined the risk factors for ectopic pregnancy in 214 patients (aged 18-44,
      mean 32 +/- 9 years) hospitalized in Department of Reproductive Medicine and
      Gynecology of Pomeranian Medical University between 1993 and 2002. The control
      group composed 215 patients admitted to the hospital outpatient clinic in the
      years 1993-2002. RESULTS: The risk factors for ectopic pregnancy evaluated in
      each group of patients were: history of adnexitis, surgical procedures
      (appendectomy, tubal microsurgery, ovarian cystectomy, adnexectomy, myomectomy,
      cesarean section, previous conservative surgical treatment of ectopic pregnancy,
      salpingectomy), appendicitis complicated by peritonitis, endometriosis,
      conservative treatment of ectopic pregnancy, insertion of IUD, ovarian induction
      or IVF procedure, uterine defects and smoking. In the examined group 104 patients
      had a history of surgery (48.5%) compare to 40 patients in the control group
      (18.6%). Difference between groups is significant p = 0,034. In 40 cases out of
      104 (18.6%) surgical operations were done two and more times. Statistics proves
      that surgical procedures in the past occurred significantly more frequently in
      the studied than in control group. The most frequent operations were:
      conservative surgical treatment of ectopic pregnancy (p = 0.000), tubal
      microsurgery (p = 0.0016), ovarian cystectomy (p = 0.013) and salpingectomy (p =
      0.047). Appendectomies or myomectomies in the past did not increase the risk of
      ectopic pregnancy. Additionally, in the examined group there were more cases of
      MTX (Methotrexate) therapy applied in the past because of ectopic pregnancy (p =
      0.000), more smoking (p = 0.0001) and more adnexitis in the past (p = 0.013).
      Treated endometriosis in the past, artificial reproductive techniques (ART),
      peritonitis, IUD application and uterine defects were no important risk factors
      for ectopic pregnancy. CONCLUSIONS: The main risk factors for ectopic pregnancy
      are: history of surgical procedures, especially conservative surgical treatment
      of ectopic pregnancy and tubal microsurgery. Appendectomy or myomectomy do not
      increase this risk. The other important risk factors for ectopic pregnancy are:
      conservative treatment of ectopic pregnancy in the past and smoking. Adnexitis is
      another risk factor for ectopic pregnancy.

PMID- 15859554
TI  - [The spectrum of congenital malformations of the urinary tract in fetuses and
      newborns in autopsies in 1989-2002].
AB  - The retrospective analysis of own autopsy findings of 831 fetuses and newborns
      with different forms of congenital malformations were carried out. In 172 cases
      (20.7%) urinary tract abnormalities were revealed. Isolated malformations
      represented 43.6% (75 cases) and 56.4% (97 cases) constituted one component of
      complex multisystem anomalies. Obstructive uropathies with different renal
      changes represented 54.7% of the isolated malformations, renal agenesis - 28%,
      autosomal recessive or dominant polycystic renal diseases - 16% and renal
      hypoplasia 1.3%. Obstructive uropathies were also most prevalent among the
      multisystem abnormalities (45.4%), while agenesis represented 34% of cases,
      horseshoe kidney - 12.4%, autosomal polycystic kidney diseases 4.1%, and renal
      hypoplasia 4.1%. Congenital abnormalities of urinary tract (especially the
      obstructive uropathies and agenesis) were more common in male fetuses and
      newborns. A highly frequent coexistence of urinary system congenital
      abnormalities and malformations of digestive tract, circulatory system and
      central nervous system were observed.

PMID- 15859555
TI  - [Acardiac fetus--morphological and clinical aspects].
AB  - The authors described 6 cases of serious complication of the multiple pregnancies
      with twin-to-twin transfusion syndrome (TTTS) sub form twin reverse arterial
      perfusion (TRAP) with development of acardiac fetus. It was established that this
      anomaly is an extremely rare complication of multiple pregnancies and very
      uncommon congenital malformation disclosed in fetuses and newborns. Acardiac
      "recipient" fetuses may have different morphological forms and often their birth
      weight is higher than that of the "donor" fetuses. The latter represent
      morphologic features of circulatory overload due to the necessity of supplying
      blood to the amorphous acardiac fetus. They are usually born preterm with
      circulatory insufficiency, intrauterine hypoxia and with developmental anomalies.
      Survival of one of the "donor" fetus implies the necessity of early diagnosis to
      detect pregnancy pathology, possible intrauterine intervention and monitoring of
      the healthy twin.

PMID- 15859556
TI  - [Some parameters of immune response in patients infected with Toxoplasma gondii].
AB  - The immune system, its cellular and humoral response, is engaged by the host
      organism to fight against parasitic invasions. The group examined consisted of 52
      women aged 18-42 years infected with Toxoplasma gondii. The diagnosis was
      established based on serologic examination. Blood for analysis was collected
      before antiparasitic treatment. Control group consisted of 32 healthy women aged
      18-46 years. The concentrations of IgM, IgG and IgE were assayed using a set of
      VIDAS (bioMerieux) and the concentrations of IL-5 were assayed using a set of
      Quantikine human IL-5 (R&D Systems). An abnormal rise in total serum IgE can be
      observed in parasitosis and allergy. IL-5 is produced mainly in T-cells in
      response to stimulation by parasite-derived antigens and allergens The present
      study revealed that (in toxoplasmosis) the concentration of IgE and IL-5 contents
      in blood serum was higher 2-times, respectively than in healthy controls.

PMID- 15859557
TI  - [Difficult questions for family physicians concerning hypertension--questionnaire
      results].
AB  - Epidemiological studies shows high percent of hypertension cases are not covered
      as well as level of hypertension control is not satisfactory. The aim of this
      study was assessment of basic level of knowledge concerning hypertension in group
      of basic health care physicians. MATERIAL AND METHODS: 846 practice family
      physicians were included in this study. The questionnaire (own creation) was used
      for investigation. Before training course, four questions were asked to
      physicians about: 1/ Hypertension diagnosis in different age groups of people, 2/
      Frequency of essential hypertension among of adult population, 3/ Blood pressure
      in first half period of normal pregnancy comparison to pre-pregnancy blood
      pressure, 4/ Groups of antihypertensive drugs certainly non administered in
      pregnancy period. RESULTS: 14% responders correctly answered for first question,
      19%for second question, 10%-for third and 6% for fourth question. CONCLUSIONS: 1.
      Investigated physicians presented low level of knowledge about hypertension. 2.
      It is necessary to elaborate more effective strategy for education of family
      physicians.

PMID- 15859558
TI  - [Pyoderma gangrenosum after a pacemaker implantation--case report].
AB  - We are presenting a 71-years old male patient with chronic skin lesions that
      appeared at multiple site of pacemaker implantations in the upper thorax. In
      spite of many treatment trials, no significant improvements were accomplished.
      Expanded dermatological tests including serial histopathological examinations
      were necessarily performed. Based on test results and clinical presentations, the
      diagnosis of pyoderma gangrenosum was made. Immediate steroid therapy allowed
      dramatic improvement of the chronic inflammatory condition. The patient is still
      undergoing a close dermatological and cardiological follow-up. Replacement of the
      pacemaker into the abdomen is currently being considered.

PMID- 15859559
TI  - [Current views on etiopathogenesis of aging].
AB  - Global aging of populations is demographic, sociologic and medical important
      phenomenon. In the paper a general demographic characteristic of aging in
      urbanized societies and a prognosis of changes were presented, Polish population
      including. Rate of aging is individual, but modified by environment factors. The
      historical review of the most important theories of aging and critical current
      estimation were discussed. The role of oxidative damage was specially emphasized
      in aging.

PMID- 15859560
TI  - [Nitric oxide in physiology and pathology of metabolism].
AB  - Adipose tissue generates many bioactive substances, which may exert autocrine,
      paracrine and endocrine effects. Recent studies have revealed, that one of these
      substances is nitric oxide. There are observed increased expressions of synthases
      NO (eNOS and iNOS) in adipose tissue in obesity. It seems that these increased
      expression NOS is reflected by increased serum concentration of NO in obese
      subjects. The review of the current literature on role of nitric oxide in
      physiology and pathology metabolism is presented in this paper.

PMID- 15859561
TI  - [Neurocutaneous melanosis and congenital gigantic pigmented nevi in the light of
      current knowledge].
AB  - The aim of this work is to approach the subject of neurocutaneous melanosis and
      to point out the necessity and precise neurological diagnosis in each case of
      gigantic pigmented nevi. It is necessary to remember about early planning of skin
      changes removal which is the cause of lowering risk of malignant melanoma.

PMID- 15859562
TI  - [Adrenal myelolipoma].
AB  - This paper is a review of the literature about adrenal myelolipoma. It is a rare,
      benign, hormonally inactive tumor of the adrenal gland composed of mature fat
      tissue and hematopoietic tissue in varying amounts. Adrenal myelolipoma is
      usually small (< 4 cm), unilateral and causes no clinical disorders. The age
      range of the affected patients is 20-90 years; most are men in their fourth to
      sixth decade. This tumour is discovered during autopsy or USG, CT MRI of the
      abdomen usually by chance and because of that is included in the group of tumors
      called incidentaloma. Etiology of myelolipoma is unclear. It is usually
      hormonally inactive but there were several cases in which adrenal myelolipoma
      coexisted with various endocrine disorders such as Cushing's syndrome, Conn's
      syndrome, Addison's disease, hirsutism, hermaphroditism, inborn deficiencies of
      17- and 21-hydroxylase. It is also more frequent in patients with obesity,
      hypertension and leading stressful life. Surgical treatment is called for when
      the diameter of tumor reaches more than 4 cm, tumour shows tendency to fast
      growth or causes clinical disorders. In cases of small lesions, that show no
      progression, it is advised to observe the tumor using imaging techniques.

PMID- 15859563
TI  - [Genetic aspects of the pathogenesis of aortic abdominal aneurysms].
AB  - In industrialized countries the number of abdominal aortic aneurysms (AAA) is
      continuously rising. In recent years the mortality rate tripled and it is the
      number 13 cause of death in United States. Despite many identified risk factors
      and understanding of their pathomechanisms, the pathogenesis of AAA remains
      unclear. Thanks to the epidemiological researches and improvement of molecular
      techniques it was noted that AAA may have a genetic bases. The diversity between
      the possible genomic defects that could lead to the development of aneurytic
      changes was also suggested. This has a direct relationship with the complexity of
      the aortic wall structure and therefore with the number of potential injury
      locations. Current genetic research confirms the changes in expression and the
      many polymorphic variants of genes coding structural and enzymatic proteins.
      Thus, AAA seems to be a disease with multifactor pathogenesis and numerous
      possible genome anomaly variants. Hence, it seems that the complete understanding
      of the genetic bases of AAA continuous to be distant. However, efforts in this
      matter remain valuable, giving hope for an improved diagnosis, prophylaxis and
      treatment of this disease. This article is a review of the available knowledge
      regarding the genetic origin of AAA.

PMID- 15859564
TI  - [Atypical forms of Borrelia burgdorferi--clinical consequences].
AB  - Borrelia burgdorferi utilizes a variety of mechanisms to counteract eradication
      by its host and establish chronic infection. We discuss several of these
      mechanisms, including plasmid encoded genes, morphologic variants, cysts
      formation, colonies formation, antigenic variation, and resistance to iron
      deprivation. These mechanisms, as well as the possible survival of Borrelia
      burgdorferi in forms with low metabolic activity, may explain relapsing Lyme
      disease, and may, also account for the difficulties with eradicating this
      pathogen.

PMID- 15859565
TI  - [Beware of bidis].

PMID- 15859566
TI  - [Data recording using a personal digital assistant. Experience of prospective
      survey on pain in 3196 patients].
AB  - OBJECTIVE: To assess the interest of a personal digital assistant (PDA) when used
      as data collector in a prospective survey on pain in general practice. METHODS:
      Prospective, multicentre and national survey concerning the identification of
      4g/24h paracetamol prescription conditions as well as the characterization of the
      pain justifying it. Data were collected with a dedicated PDA including an
      electronic visual analogue scale (VAS). It also included a data controlling
      program of probability, consistency, date recording and time of data entry.
      RESULTS: 3.196 patients were enrolled by 830 general practitioners (GPs). For
      1.066 of them enrolled by 277 GPs, the consistency analysis showed an a
      posteriori data entry. However, for assessment of pain intensity using the VAS,
      the physical presence of the patient is mandatory because self-evaluation is the
      rule. CONCLUSION: The use of an electronic questionnaire permits the collection
      of good quality data and the possibility of a posteriori control and hence the
      identification of breaches in clinical trial protocols.

PMID- 15859567
TI  - [Epidemiology of seasonal spring-time allergic rhinitis in adults in France].
AB  - OBJECTIVE: Describe the profile of patients consulting a general practitioner or
      allergologist for seasonal spring-time allergic rhinitis (SAR) in France.
      METHODS: 3.348 physicians (3.284 general practitioners and 64 allergologists)
      recruited in 4 monthly episodes from March to June 1998, 34.851 patients
      consulting for SAR. Using a questionnaire, demographical data concerning the
      practitioners consulted and all the patients were collected. For 12,420 patients
      the symptomatology, history of asthma and ongoing treatment for SAR were analysed
      by comparing the population consulting a general practitioner (A) or an
      allergologist (B). RESULTS: Mean age for all patients with suspected SAR was of
      37.1 +/- 15.7 years with a majority of women (54.90%). For 1,441 patients, it was
      the first consultation for this disorder, notably with a general practitioner,
      (11.1 vs. 2.4%). Aqueous rhinorrhea, sneezing and nasal obstruction were the most
      frequent symptoms noted, without significant difference between the type of
      practitioner consulted. 5.711 patients had undergone previous allergy tests, with
      more skin tests in the group consulting an allergologist (78 vs. 44.9%).
      Association with history of asthma was similar in both groups (30%). Impact on
      daily life was almost identical, whether isolated or associated with past history
      of asthma (56 vs. 51.6%), but differed with regard to sleep (56.7 vs. 21.1%).
      During the consultation, 5.889 patients were already treated with antihistamines
      (83.2%), whatever the type of practitioner consulted. CONCLUSION: Seasonal spring
      time allergic rhinitis is a frequent pathology, which significantly impairs
      quality of life. There is little difference in patients' profile whether they
      consult a general practitioner or an allergologist.

PMID- 15859568
TI  - [Tuberculosis and infliximab treatment. National surveillance from January 1,
      2000, through June 30, 2003].
AB  - OBJECTIVES: Analysis of the tuberculosis cases reported in France in patients
      treated with infliximab since its marketing approval, assessment of the effect of
      changes in the summary of product characteristics and national guidelines.
      METHODS: Based on tuberculosis reports from the national post-marketing adverse
      drug reaction databank of the manufacturer from January 1, 2000 through June 30,
      2003, and records from the national multicenter retrospective survey on
      opportunistic infections with anti-TNFalpha, we analyzed all cases of
      tuberculosis and the impact of the changes made in December 2000 in the summary
      of product characteristics and the guidelines on the prevention and management of
      tuberculosis in patients treated with infliximab published in February 2002.
      RESULTS: 56 cases of tuberculosis were reported: the median interval before
      diagnosis was 12 weeks with a median of 3 infusions. The presence of Koch bacilli
      was confirmed in 32 patients; 29 patients had extrapulmonary or disseminated
      forms of tuberculosis. The tuberculosis rate among patients treated with
      infliximab was greater than among the general population and differed
      significantly by period (p < 0.005). CONCLUSION: Tuberculosis can occur within
      the first 12 weeks of treatment with infliximab. Information for practitioners
      must be continued, together with surveillance of the tuberculosis cases in
      France.

PMID- 15859569
TI  - [Low vitamin B12 levels in elderly patients cured within one week by oral
      cobalamin therapy].
AB  - OBJECTIVE: Non-dissociation of vitamin B12 from its carrying proteins is the most
      frequent cause of vitamin B12 deficiency in the elderly. The aim of this study
      was to determine the initial dose of oral cyanocobalamin that would correct the
      B12 vitamin deficiency within one week. METHODS: This was an open, prospective,
      study on 30 elderly patients suffering from vitamin deficiency (B12 < 0.20
      microg/L) induced by food-cobalamin malabsorption. Ten patients (group I) were
      treated with a daily dose of 1000 microg of oral cyanocobalamin (from D1 to D8),
      10 (group II) with 1000 microg every other day (D1, D3, D5 and D7), 5 (group III)
      with 1000 microg every 4 days (D1 and D5) and 5 (group IV) with 1000 microg only
      on D1. The biological response was assessed by control measurement of vitamin B12
      serum levels on the 8th day. RESULTS: Mean vitamin B12 serum levels had
      significantly increased (p < 0.01) in groups I, II and III, but not in group IV.
      The dose-effect, assessed by the mean increase in vitamin B12 serum levels, was
      significantly greater (p < 0.05) in groups I (0.25 microg/L) and II (0.18
      microg/L), than in groups III and IV (0.09 microg/L). CONCLUSION: This
      prospective study shows that an oral dose of 1000 microg of cyanocobalamin every
      4 days, which corresponds to 250 microg per day, was sufficient to correct B12
      vitamin deficiency induced by food-cobalamin malabsorption within one week.
      However, initial doses of 1000 microg per day or every other day would be
      preferable because of the greater dose-effect with daily doses higher than 500
      microg. A randomised study is warranted to validate these preliminary results.

PMID- 15859570
TI  - [Recurrent pericarditis revealing a malignant mediastinal mesenchymoma].
AB  - INTRODUCTION: The malignant mesenchymoma is a malignant tumour composed of two or
      more types of non-differentiated tissue, associated with fibrosarcomatous
      elements. Its mediastinal localisation is exceptional. OBSERVATION: In a 65 year
      old woman, recurrent pericardial effusion revealed a malignant mesenchymoma
      measuring 11 x 9 x 4 cm, located in the mediastinum and extending towards the
      pericardium. The histological examination of the surgical piece showed the
      predominance of an osteo-sarcomatous component. Complete resection was performed
      with partial pericardectomy, followed by adjuvant radiotherapy. CONCLUSION:
      Malignant mediastinal mesenchymoma is an exceptional tumour. Its diagnosis is
      based on anatomopathological study of a mass of anarchic composition, and its
      poor prognosis is related to its localisation and its capacity to relapse
      locally.

PMID- 15859571
TI  - [Severe Graves' acropachy and dermopathy. Three case reports].
AB  - INTRODUCTION: Traditionally described, severe Graves' acropachy and tibial
      myxoedema are now only encountered in certain severe forms of Graves' disease,
      where they can be difficult to diagnose and hence delay the initiation of
      treatment. OBSERVATIONS: Three patients presented with severe ophthalmopathy,
      pretibial myxoedema and acropachy of different clinical forms. DISCUSSION: In
      supplement to the usual biopsies and X-rays, bone scintigraphy provides early
      diagnosis of acropachy. The severity of the immune disease, the episodes of
      hypothyroidism and cigarette smoking are the 3 main factors contributing to these
      extra-thyroid manifestations of Graves' disease. There is currently no treatment
      that can permanently resolve the functional and aesthetic problems of dermopathy
      and acropachy.

PMID- 15859572
TI  - [Relapse of Plasmodium malariae malaria 20 years after living in an endemic
      area].
AB  - INTRODUCTION: Malaria has been eradicated in Tunisia since 1979. Although it
      continues to be evoked in the case of fever after travel to an endemic zone, its
      diagnosis is however difficult during relapses, notably when they are delayed.
      OBSERVATION: A 50 year-old man having lived in Mauritania from 1978 to 1982 was
      hospitalized for interstitial pneumopathy and urarthritis. In spite of treatment
      with broad spectrum antibiotics, the fever accompanied by abundant sweating
      persisted. A thick blood drop and blood smear was requested and led to the
      diagnosis of Plasmodium malariae malaria. DISCUSSION: This observation recalls
      the possibility of parasitic upsurge of some plasmodial species. It should prompt
      physicians to be careful and evoke malaria in the case of fever in subjects
      having stayed, even several years before, in an endemic zone. This would permit
      early diagnosis and treatment.

PMID- 15859573
TI  - [Fibrodysplasia ossificans progressiva in children. The interest of early
      diagnosis and treatment].
AB  - INTRODUCTION: A rare genetic disease (with around a hundred cases in France),
      fibrodysplasia ossificans progressiva is characterized by heterotopic
      ossification and congenital malformation of the bones. It is worsened by physical
      trauma, progresses in successive flares and slowly results in total confinement
      of the children because of the calcification of the muscles and ankylosis of all
      the joints. OBSERVATIONS: We report the case of two children exhibiting
      fibrodysplasia ossificans progressiva in whom diagnosis was delayed at the age of
      4 and 18 months respectively. DISCUSSION: Fibrodysplasia ossificans progressiva
      must be diagnosed during the neonate period. Early treatment will help to avoid
      the factors of aggravation, slow the progression of the disease and provide the
      children with improved quality of life. Unfortunately, there is no efficient
      treatment, bisphosphonates and corticosteroids are only beneficial during the
      flares. Hope for the future relies on gene therapy.

PMID- 15859574
TI  - [About the person of trust].

PMID- 15859575
TI  - [Osteoporosis and hormone replacement therapy].
AB  - Hormone replacement therapy prevents bone loss and the increase in bone
      resorption due to the hormone deficiency in oestrogen in postmenopausal women.
      The WHI (Women's Health Initiative) randomised, double-blind study against
      placebo, demonstrated that which all the epidemiological trials had already
      suggested: replacement therapy can reducing by around 30% the risk of fractures
      in postmenopausal women. Administration of hormone replacement therapy requires
      account being taken of (in view of the uncertainties regarding the anti-fracture
      effect of low dose therapy): the duration (in view of the absence of remnant
      effect of the product on bone loss and on the risk of fracture) and the
      benefit/risk ration (in view of the benefits demonstrated on climacteric
      disorders, but the increase in risk of breast cancer). The menopause is the
      occasion to assess individual risks, notably vascular and of fractures, taking
      into account the clinical risk factors and measurement of bone density.

PMID- 15859576
TI  - [Sarcomas of the small intestine].
AB  - Sarcomas of the small intestine are rare, clearly differentiated, malignant,
      mesenchymatous tumours that can be of smooth muscle, Schwann cell or fibroblastic
      origin. From a clinical point of view, the pain and abdominal mass are the 2
      types of symptoms that frequently reveal the disease. In rare cases, sarcomas of
      the small intestine are manifested by an acute complication. No imaging method
      can clearly confirm the diagnosis. Before immunohistochemistry, differential
      diagnosis was made on undifferentiated mesenchymatous "stromal" tumours, which
      are also rare. Exeresis must be complete and without perforation of the tumour
      because of the risk of locoregional relapse. The benefits provided by
      chemotherapy and radiotherapy are limited because of the low mitotic activity of
      the tumour cells and its weak vascularisation. Long-term survival is limited by
      poor prognosis criteria: high grade malignancy, size greater than 5 cm, tumour
      extension, perforation of the tumour, quality of surgical resection and
      histological type.

PMID- 15859577
TI  - [Hantavirus infections].
AB  - Hantaviruses are cosmopolite anthropozoonosis considered as an emerging disease.
      Four pathogenic types for humans and part of the Bunyaviridae species are hosted
      by rodents and have been isolated: the Sin nombre virus responsible for the
      severe American respiratory form; the Hantaan and Seoul viruses responsible for
      hemorrhagic fevers with renal syndrome (HFRS) of severe to moderate expression in
      Asia and also in the Balkans; the Puumala virus responsible for HFRS of moderate
      expression or the socalled nephropathia epidemica in Europe. The Puumala virus is
      responsible for a minor form of the disease that is observed in areas of the
      Occidental sector of the ex-URSS, in Scandinavia and in the rest of Europe,
      notably in the North-East of France. The epidemic episodes occur every three
      years. They follow the proliferation of rodents, notably russet voles, the
      reservoir hosts, and their degree of infection. The concept of an occupation at
      risk in 20 to 49 year-old men (working in forests, agriculture, living near a
      forest, contact with wood) in an endemic area has not always been found. Its
      clinical form can vary greatly in its presentation. Basically it is a severe
      algic influenza syndrome accompanied by acute myopia in 38% of cases, but is
      nearly pathognomonic in the context. Respiratory involvement is frequent but
      benign. The initial syndrome can suggest an abdominal or urological surgical
      emergency, which is source of diagnostic and therapeutic errors. Early biological
      examination reveals thrombopenia and proteinuria. Then more or less severe acute
      kidney failure appears in slightly more than 50% of cases. Although it usually
      regresses with symptomatic treatment, after effects remain in some patients. The
      environmental changes, the geographical distribution depending on the biotope,
      the dynamics and behaviour of rodents and the viral circulation between them and
      its transmission to human beings and its risk factors must continue to be studied
      in order to gain further knowledge on the epidemiology of this anthropozoonosis.

PMID- 15859578
TI  - [Traumatic rupture of the aortic isthmus].

PMID- 15859579
TI  - [A thrombin inhibitor called ximelagatran].

PMID- 15859580
TI  - Characterization of a novel modification to monoclonal antibodies: thioether
      cross-link of heavy and light chains.
AB  - A novel, nonreducible thioether bridge between the light and heavy chains of
      different IgG1 monoclonal antibodies has been characterized. An additional band
      with an apparent molecular weight of 92 kDa was detected when monoclonal
      antibodies were analyzed by reducing capillary gel electrophoresis (rCGE) and
      reducing SDS-PAGE. To further investigate this observation, an early-eluting peak
      in the size exclusion chromatogram of a reduced and alkylated monoclonal antibody
      was collected and characterized by liquid chromatography, mass spectrometry, and
      gel electrophoresis. The reduced and alkylated Mab was shown to be a cross-linked
      adduct with a molecular weight of 75 kDa. In the adduct, the heavy and light
      chains of the antibody were cross-linked by a nonreducible thioether bond between
      Cys-223 of the heavy chain and the C-terminal Cys residue of the light chain. The
      thioether bond modification was confirmed in the Fab fragment of a monoclonal
      antibody by LC-MS and nonreduced Lys-C peptide mapping with tandem mass
      spectrometry. The data show that the disulfide bond modification occurred under
      nonreducing conditions and was not an artifact of sample preparation for the rCGE
      analysis. The thioether bond modification was observed in several IgG1 monoclonal
      antibody products. Structural characterization of this novel modification is
      important in understanding the mechanism of thioether bond formation.

PMID- 15859581
TI  - Ultrasensitive reporter protein detection in genetically engineered bacteria.
AB  - We demonstrate the use of laser-induced fluorescence confocal spectroscopy to
      measure analyte-stimulated enhanced green fluorescent protein (egfp) synthesis by
      genetically modified Escherichia coli bioreporter cells. Induction is measured in
      cell lysates and, since the spectroscopic focal volume is approximately the size
      of one bioreporter cell, also in individual live bacteria. This is, to our
      knowledge, the first ever proof-of-concept work utilizing instrumentation with
      single-molecule detection capability to monitor bioreporter response. Although we
      use arsenic inducible bioreporters here, the method is extensible to gfp/egfp
      bioreporters that are responsive to other substances.

PMID- 15859582
TI  - Magnetically actuated complementary metal oxide semiconductor resonant cantilever
      gas sensor systems.
AB  - In the present paper, an electromagnetically actuated resonant cantilever gas
      sensor system is presented that features piezoresistive readout by means of
      stress-sensitive MOS transistors. The monolithic gas sensor system includes a
      polymer-coated resonant cantilever and the necessary oscillation feedback
      circuitry, both monolithically integrated on the same chip. The fully
      differential feedback circuit allows for operating the device in self-oscillation
      with the cantilever constituting the frequency-determining element of the
      feedback loop. The combination of magnetic actuation and transistor-based readout
      entails little power dissipation on the cantilever and reduces the temperature
      increase in the sensitive polymer layer to less than 1 degrees C, whereas
      previous designs with thermally actuated cantilevers showed a temperature
      increase of up to 19 degrees C. The lower temperature of the sensitive polymer
      layer on the cantilever directly improves the sensitivity of the sensor system as
      the extent of analyte physisorption decreases with increasing temperature. The
      electromagnetic sensor design shows an almost 2 times larger gas sensitivity than
      the earlier design, which is thermally actuated and read out using p-diffused
      resistors. The gas sensor is fabricated using an industrial complementary metal
      oxide semiconductor (CMOS) process and post-CMOS micromachining.

PMID- 15859583
TI  - Chemical sensor based on microfabricated wristwatch tuning forks.
AB  - We report here a chemical sensor based on detecting the mechanical response of a
      thin (approximately 10-microm) polymer wire stretched across the two prongs of a
      wristwatch quartz tuning fork (QTF). When the fork is set to oscillate, the wire
      is stretched and compressed by the two prongs. The stretching/compression force
      changes upon adsorption of analyte molecules onto/into the polymer wire, which is
      detected by the QTF with pico-Newton force sensitivity. An array of such sensors
      with different polymer wires is used for simultaneous detection of several
      analytes and for improvement of pattern recognition. The low cost (approximately
      10 cent) of the QTF, together with that an array of QTFs can be driven to
      oscillate simultaneously and their resonance frequencies detected with the same
      circuit, promises a high performance, low cost, and portable sensor for detecting
      various chemical vapors. We demonstrate here detection of parts-per-billion-level
      water, ethylnitrobenzene, and ethanol vapors using the QTF arrays.

PMID- 15859584
TI  - Dielectrophoretic segregation of different human cell types on microscope slides.
AB  - A new method for preparing cells for microscopic examination is presented in
      which cell mixtures are fractionated by dielectrophoretic forces and
      simultaneously collected into characteristic zones on slides. The method traps
      cells directly from the suspending medium onto the slide, reducing cell loss.
      Furthermore, it exploits differences in the dielectric properties of the cells,
      which sensitively reflect their morphology. Because different cell types are
      trapped in characteristic zones on the slide, the technique represents an advance
      over existing methods for slide preparation, such as centrifugation and smears
      where cells are randomly distributed. In particular, the new method should aid in
      the detection of rare and anomalous cell subpopulations that might otherwise go
      unnoticed against a high background of normal cells. As well as being suitable
      for traditional microscopic examination and automated slide scanning approaches,
      it is compatible with histochemical and immunochemical techniques, as well as
      emerging molecular and proteomic methods. This paper describes the rationale and
      design of this so-called electrosmear instrumentation and shows experimental
      results that verify the theory and applicability of the method with model cell
      lines and normal peripheral blood subpopulations.

PMID- 15859585
TI  - Automated sequential injection-microcolumn approach with on-line flame atomic
      absorption spectrometric detection for implementing metal fractionation schemes
      of homogeneous and nonhomogeneous solid samples of environmental interest.
AB  - An automated sequential injection (SI) system incorporating a dual-conical
      microcolumn is proposed as a versatile approach for the accommodation of both
      single and sequential extraction schemes for metal fractionation of solid samples
      of environmental concern. Coupled to flame atomic absorption spectrometric
      detection and used for the determination of Cu as a model analyte, the potentials
      of this novel hyphenated approach are demonstrated by the ability of handling up
      to a 300 mg sample of a nonhomogeneous sewage amended soil (viz., CRM 483). The
      three steps of the endorsed Standards, Measurements, and Testing sequential
      extraction method have been also performed in a dynamic fashion and critically
      compared with the conventional batchwise protocols. The ecotoxicological
      relevance of the data provided by both methods with different operationally
      defined conditions is thoroughly discussed. As compared to traditional batch
      systems, the developed SI assembly offers minimal risks of sample contamination,
      the absence of metal re-distribution/readsorption, and dramatic saving of
      operational times (from 16 h to 40-80 min per partitioning step). It readily
      facilitates the accurate manipulation of the extracting reagents into the flow
      network and the minute, well-defined injection of the desired leachate volume
      into the detector. Moreover, highly time-resolved information on the ongoing
      extraction is given, which is particularly relevant for monitoring fast leaching
      kinetics, such as those involving strong chelating agents. On-line and off-line
      (for Cu, Pb, and Zn) single extraction schemes are also proven to constitute
      attractive alternatives for fast screening of metal pollution in solid samples
      and for predicting the current, rather than the potential, element
      bioavailability by the assessment of the readily mobilizable metal forms.

PMID- 15859586
TI  - pHluorin-based in vivo assay for hydrolase screening.
AB  - pHluorin, a pH-sensitive mutant of green fluorescent protein (GFP), acts as a
      sensor for intracellular pH shifts, triggered by hydrolytic enzymes. This
      principle was used to develop a pHluorin-based in vivo assay for hydrolase
      screening. The presented assay was evaluated for Escherichia coli (E. coli)
      cells, producing heterologous pHluorin and an esterase from Geobacillus
      stearothermophilus which is considered as a model hydrolase. Subsequently, the
      utility of this detection system was also demonstrated with recombinantly
      expressed hydantoinase and amidase in E. coli. This in vivo assay also shows
      capability for readout with flow cytometric devices. Population shifts of
      pHluorin-expressing E. coli cells were easily recognized due to pH changes caused
      by substrate hydrolysis.

PMID- 15859587
TI  - Combined system for the simultaneous optical and electrochemical monitoring of
      intra- and extracellular NO produced by glioblastoma cells.
AB  - A combined, optospectroscopic and electrochemical assay system for the
      simultaneous monitoring of intra- and extracellular production of biologically
      important species has been developed and assessed. The present model system
      evaluates intra- and extracellular nitric oxide produced by stimulated
      glioblastoma multiform cell line (A172). The production of endogenous NO was
      induced by phorbol-12-myristate-13-acetate and inhibited by N(omega)-nitro-l
      arginine methyl ester. Intracellular production of NO was monitored via
      fluorescence image analysis using a 4,5-diaminofluorescein probe, while
      extracellular NO release was monitored via a chemically modified electrode, which
      was incorporated into an optically transparent cell chip. The results indicated
      that there was no mutual interference between the optical and electrochemical
      measurement systems. The response time of the combined optical/electrochemical
      system was found to be in the range of a few tens of seconds.

PMID- 15859588
TI  - Assessing reproducibility of a protein dynamics study using in vivo labeling and
      liquid chromatography tandem mass spectrometry.
AB  - Measuring dynamics of proteins abundance in cells in response to stimuli such as
      growth factors or drugs requires analysis of more than one time point. Proteomic
      approaches have traditionally been used to measure only one state at a time
      because quantitation is difficult, especially when mass spectrometry is used as a
      readout. Isotopically labeled reagents have recently been introduced that allow
      comparison of two or three different states by mass spectrometry. Here, we
      evaluate the reproducibility of an experiment that measures three states
      simultaneously through stable isotope labeling of cells with amino acids in cell
      culture (SILAC) using light, medium, and heavy versions of amino acids. The major
      goal of this study was to assess the reproducibility of such experiments in
      combination with liquid chromatography tandem mass spectrometry (LC-MS/MS). Our
      results show that it is possible to obtain reproducible quantitative data to
      study protein dynamics based on our analysis of more than 220 peptide sets
      derived from 20 proteins from 3 different LC-MS/MS runs.

PMID- 15859589
TI  - Protein pI shifts due to posttranslational modifications in the separation and
      characterization of proteins.
AB  - Proteins from breast cancer cell lines are characterized using a 2-D liquid
      separation technique in which protein pI is used as the first-dimension
      separation parameter. To effect this protein pI separation, chromatofocusing(CF)
      is employed whereby a pH gradient is generated on-column using a weak anion
      exchange medium with the intact proteins fractionated and collected every 0.2 pH
      unit. It is demonstrated that the pI for expressed intact proteins as generated
      by CF is an important parameter for identification and characterization of the
      actual protein modifications occurring in the cancer cell. For most proteins, the
      experimentally determined pI is very close to that predicted by the databases. In
      other cases, however, where the pI is observed to be shifted from the expected
      value, it is shown that this shift is often correlated to protein modifications.
      The modifications that cause such shifts include truncations and deletions often
      observed in cancer cells or phosphorylations that can shift the pI by several pH
      units. It is also shown that the effects of phosphorylation on the observed shift
      can vary depending upon the protein and the amount of phosphorylation. Moreover,
      large changes in the pI are often observed for proteins with a pI above 7.0 upon
      phosphorylation, whereas little change is observed for proteins with a pI of
      approximately 5.0. The expressed protein's pI value thus becomes an important
      parameter together with the intact MW value, peptide map, and MS/MS results for
      identification of the presence and type of posttranslational modifications
      occurring in the cancer cell.

PMID- 15859590
TI  - Simultaneously amplified electrochemical and surface plasmon optical detection of
      DNA hybridization based on ferrocene-streptavidin conjugates.
AB  - A sensitive method based on ferrocene-streptavidin (Fc-Stv) conjugates for the
      simultaneously amplified electrochemical and surface plasmon optical detection of
      DNA target hybridization to peptide nucleic acid-modified gold surfaces is
      reported. The attachment of Fc-Stv to the biotinylated complementary target DNA
      not only amplified the surface plasmon resonance signal but also enhanced the
      electrochemical signal due to the many Fc markers per Stv. The ferrocene redox
      peak current increased with the increase of the target DNA concentration.
      Consequently, the amount of hybridized target DNA can be estimated by cyclic
      voltammetry and chronocoulometry. The detection limit of this DNA sensor is 10 pM
      (2 fmol, with signal to noise > 3). This sensor was also shown to have high
      selectivity (at the single-base mismatch level) and good reproducibility.

PMID- 15859591
TI  - Multisensor system for characterization of packaging emissions: prediction of
      total solvent amount and odor scores.
AB  - This work shows a fast and economic screening of packaging materials for food
      using a multisensor system. The multisensor system comprises a sampling system
      (in most cases a headspace sampler), a sensor array, and operation and evaluation
      electronics. The added value of the inclusion in the sampling system of a
      separation unit (e.g., chromatographic column) was proved for two different
      cases. The first is the elimination of a major interfering gas (e.g., water
      vapor); this was achieved with a short packed polar column that separated water
      vapor and organic solvents into two peaks. The second case is the extension of
      the correlation capability to human sensory panels. This was made possible by the
      use of a long capillary column that separates the high-concentration solvent
      components, which might not have a strong odorous effect, from the trace odorous
      ones. The latter are thus detected due to the high sensitivity of the sensor
      array.

PMID- 15859592
TI  - Determination of the encapsulation efficiency of individual vesicles using single
      vesicle photolysis and confocal single-molecule detection.
AB  - This paper describes a new method to measure the encapsulation efficiency of
      individual lipid vesicles. Single vesicles were first optically trapped (with a
      CW Nd:YAG laser at 1064 nm) and then photolyzed with a single 3-ns UV laser pulse
      (from a N(2) laser at 337 nm) to release the molecules encapsulated within the
      vesicle; confocal detection with single-molecule sensitivity (laser excitation at
      488 nm from a CW Ar(+) laser) was used to measure the number of released
      molecules. By placing the confocal probe volume a few micrometers from the
      vesicle and by monitoring the transit times and the number of released molecules
      that crossed this probe volume, we could calculate the total number of molecules
      released from the vesicle using a three-dimensional diffusion equation. Unlike
      traditional definitions of encapsulation efficiencies based on bulk assays,
      because we can measure the contents of and release from individual vesicles, we
      can define the encapsulation efficiency by dividing the concentration of
      molecules encapsulated in each vesicle over the original concentration of the
      molecules present in the loading solution. We characterized the encapsulation
      efficiency of carboxyfluorescein for vesicles prepared by rotary evaporation and
      found oligolamellar vesicles have an encapsulation efficiency of 36.3 +/- 18.9%,
      while multilamellar vesicles have an encapsulation efficiency of 17.5 +/- 8.9%.

PMID- 15859593
TI  - GCxMS of diesel: a two-dimensional separation approach.
AB  - Comprehensive two-dimensional gas chromatography can be viewed as a traditional
      gas chromatography with a sophisticated "elution-resolved" flame ionization
      detector (GC/FID) or a detector with separation capability. The concept of
      multidimensional chromatography can be extended to other detectors that also have
      separation capability, such as ultraviolet, infrared, and mass spectrometer. Mass
      spectrometry, combined with gas chromatography, GC/MS, has been a powerful
      separation/identification device for many years. However, if one applies the
      multidimensional separation concept to this combination with a nonfragmentation
      ionization method, GC/MS not only can be used as a separation/identification
      tool, but also a two (multiple) dimensional separation device, GCxMS. In this
      study, a two-dimensional separation (GCxMS) study of diesel composition is
      demonstrated and compared with the GCxGC technique. The major advantage of GCxMS
      is the compound class separation. The compound groups within a compound class are
      also well-separated on the basis of their parent masses. Because of the exact
      mass operation, the specific element containing compound distribution can also be
      generated through the extraction of specific mass groups. For qualitative
      analysis, GCxMS is a technique where one experiment can generate a wide range of
      information. GCxMS may also perform quantitative analysis when appropriate
      response factors for various compound groups are available. From GCxGC to GCxMS,
      the power of two (multiple) dimensional separation has just started exposing its
      advantages for complex mixture analysis. To achieve multiple dimensional
      separation in different forms, many improvements remain to be made. The challenge
      now is to combine/accommodate two or more different techniques to solve a
      specific complex separation problem. The GCxMS experience has pushed this effort
      one step ahead toward complete application of this new concept in the analysis of
      complex mixtures.

PMID- 15859594
TI  - Electrically heated, air-cooled thermal modulator and at-column heating for
      comprehensive two-dimensional gas chromatography.
AB  - An instrument for comprehensive two-dimensional gas chromatography (GCxGC) is
      described using an electrically heated and air-cooled thermal modulator requiring
      no cryogenic materials or compressed gas for modulator operation. In addition, at
      column heating is used to eliminate the need for a convection oven and to greatly
      reduce the power requirements for column heating. The single-stage modulator is
      heated by current pulses from a dc power supply and cooled by a conventional two
      stage refrigeration unit. The refrigeration unit, together with a heat exchanger
      and a recirculating pump, cools the modulator to about -30 degrees C. The
      modulator tube is silica-lined stainless steel with an internal film of
      dimethylpolysiloxane. The modulator tube is 0.18 mm i.d. x 8 cm in length. The
      modulator produces an injection plug width as small as 15 ms.

PMID- 15859595
TI  - Utilization of cell-sized lipid containers for nanostructure and macromolecule
      handling in microfabricated devices.
AB  - We propose an original approach to handle submicrometer-sized biological or
      inorganic materials in microfabricated devices for micro total analysis
      applications. Cell-sized liposomes were utilized as containers for nanoparticles,
      green fluorescent proteins, or DNA and handled within a microfluidic chip. Due to
      the micrometer size of these liposomes, their detection could be achieved by
      conventional optical systems. Moreover, liposomes are hardly sensitive to
      Brownian motion; their trapping or transportation is thereby made easy with
      electrostatic-based techniques, for instance, developed the past few years for
      cells and particles. Encapsulated materials were confined for long durations with
      respect to the diffusive scale time, and the liposome membrane provided excellent
      protection from the outside environment, inhibiting undesirable interactions. A
      microfluidic device consisting of a flow cell covering an array of asymmetric
      electrodes allowed us to convey readily liposomes by the AC electroosmosis
      effect. We also assessed the electrofusion of liposomes between micromachined
      electrodes, opening up controlled initiation of reaction inside these containers;
      it was exemplified by fusing differently colored liposomes. We observed that a
      large fraction of the liposomes fused for electric field intensity around 6
      kV/cm. Applications ranging from ultrasmall biomimetic reactors to large-scale
      drug delivery or cell labeling can be envisaged.

PMID- 15859596
TI  - Use of multidimensional lectin affinity chromatography in differential
      glycoproteomics.
AB  - This paper reports studies comparing the relative degree of sialylation among
      human serum glycoproteins carrying complex biantennary N-linked, hybrid, and high
      mannose oligosaccharides. Comparisons were made by coupling lectin affinity
      selection with stable isotope coding of peptides from tryptic digests of serum.
      After proteolysis, samples were split and differentially acetylated with stable
      isotope coding agents according to either origin or the separation method by
      which they would be fractionated. A lectin column prepared from Sambucus nigra
      agglutinin (SNA) was used to select and compare the concentration of sialic acid
      containing glycopeptides. The relative standard deviation in quantification using
      this method was 4%. Using this method the concentration of sialic acid containing
      glycoproteins from a normal individual were compared to those in a pooled serum
      sample from a large number of normal individuals. It was found that sialylation
      varied less than 2-fold in all but four or five glycoproteins. Further studies
      were done on the degree of sialylation within glycoproteins. Samples labeled with
      the light isoform of the coding agent were applied to a set of serial lectin
      columns consisting of a concanavalin A (Con A) column coupled to an SNA column
      for selecting sialic acid appended to glycopeptides with complex biantennary N
      linked, hybrid, and high-mannose glycans. In contrast, samples labeled with the
      heavy isoform of the coding agent were applied to a Con A lectin column alone to
      select glycopeptides containing complex biantennary N-linked, hybrid, and high
      mannose glycans, without regard to sialylation. Glycopeptides thus selected were
      mixed, deglycosylated by PNGase F, and fractionated by reversed-phase
      chromatography (RPC). The RPC fractions were then analyzed by ESI-MS. The
      relative standard deviation of the method was 4%. All glycopeptides identified
      contained sialic acid except one. Peptides in which the relative abundance of
      isotopic isoforms was equal were considered to indicate that the protein parent
      was fully sialylated at that specific glycosylation site.

PMID- 15859597
TI  - Characterization of quaternary ammonium oligomers by paired-ion reversed-phase
      liquid chromatography-mass spectrometry.
AB  - The separation of novel permanently charged oligomers was studied using paired
      ion reversed-phase liquid chromatography. The polyionene studied is less than 5
      kDa in size, but contains three oligomer series with different end-group
      chemistries. The complexity of this polyionene makes development of a single
      dimension separation quite challenging. Separation under critical conditions was
      employed to fractionate the end-group conformations and then the chain length of
      the oligomers in each series was confirmed by LC-MS. The oligomers were then used
      to optimize a single-dimension HPLC separation. Precise modulation of the
      hydrophobicity of the ion-pair reagent and the stationary-phase chemistry yielded
      very high resolution one-dimensional separations.

PMID- 15859598
TI  - Quantitation and accurate mass analysis of pesticides in vegetables by LC/TOF-MS.
AB  - A quantitative method consisting of solvent extraction followed by liquid
      chromatography/time-of-flight mass spectrometry (LC/TOF-MS) analysis was
      developed for the identification and quantitation of three chloronicotinyl
      pesticides (imidacloprid, acetamiprid, thiacloprid) commonly used on salad
      vegetables. Accurate mass measurements within 3 ppm error were obtained for all
      the pesticides studied in various vegetable matrixes (cucumber, tomato, lettuce,
      pepper), which allowed an unequivocal identification of the target pesticides.
      Calibration curves covering 2 orders of magnitude were linear over the
      concentration range studied, thus showing the quantitative ability of TOF-MS as a
      monitoring tool for pesticides in vegetables. Matrix effects were also evaluated
      using matrix-matched standards showing no significant interferences between
      matrixes and clean extracts. Intraday reproducibility was 2-3% relative standard
      deviation (RSD) and interday values were 5% RSD. The precision (standard
      deviation) of the mass measurements was evaluated and it was less than 0.23 mDa
      between days. Detection limits of the chloronicotinyl insecticides in salad
      vegetables ranged from 0.002 to 0.01 mg/kg. These concentrations are equal to or
      better than the EU directives for controlled pesticides in vegetables showing
      that LC/TOF-MS analysis is a powerful tool for identification of pesticides in
      vegetables. Robustness and applicability of the method was validated for the
      analysis of market vegetable samples. Concentrations found in these samples were
      in the range of 0.02-0.17 mg/kg of vegetable.

PMID- 15859599
TI  - Simultaneous use of time-resolved fluorescence and anti-stokes photoluminescence
      in a bioaffinity assay.
AB  - A bioaffinity assay is described where anti-Stokes photoluminescence of inorganic
      lanthanide phosphors and time-resolved fluorescence of lanthanide chelates are
      measured from a single microtitration well without any disturbance from these
      label technologies to each other. Up-converting phosphor (UPC-phosphor)
      bioconjugate was produced by grinding the commercial, micrometer-sized UPC
      phosphors to colloidal, submicrometer-sized phosphor particles and by attaching
      these phosphors to biomolecules. Experiments were carried out in standard 96-well
      microtitration plates to determine detection limits, linearity, and cross-talk of
      UPC-phosphor and europium chelate. In numbers of molecules the lower limits of
      detection for UPC-phosphor were roughly 3 x 10(3) particles in solution and 1 x
      10(4) particles in solid phase, and for europium label same values were 9 x 10(6)
      and 9 x 10(7) molecules. Linearity of detection was for UPC-phosphor 5 orders of
      magnitude in solution and over 4 orders of magnitude in solid phase and for
      europium label over 5 orders of magnitude in solution and over 4 orders of
      magnitude in solid phase. The cross-talk between the two labels was practically
      nonexistent. In this study we show that up-converting anti-Stokes
      photoluminescent phosphors could be employed in bioaffinity assays as very
      potential labels with significant advantages either alone or together with long
      lifetime lanthanide chelates.

PMID- 15859600
TI  - Electrochemical bioassay utilizing encapsulated electrochemical active
      microcrystal biolabels.
AB  - A new approach to perform electrochemical immunoassay based on the utilization of
      encapsulated microcrystal was developed. The microcrystal labels create a
      "supernova effect" upon exposure to a desired releasing agent. The microcrystal
      cores dissolve, and large amounts of signal-generating molecules diffuse across
      the capsule wall into the outer environment. Layer-by-Layer (LbL) technology was
      employed for the encapsulation of electrochemical signal-generating microcrystals
      (ferrocene microcrystals). The encapsulated microcrystals were conjugated with
      antibody molecules through the adsorption process. The biofunctionalized
      microcrystals were utilized as a probe for immunoassays. The microcrystal-based
      label system provided a high-signal molecule to antibody (S/P) ratio of 10(4)
      10(5). Microcrystal biolabels with different antibody surface coverage (1.60-5.05
      mg m(-2)) were subjected to a solid-phase immunoassay for the detection of mouse
      immunoglobulin G (M-IgG) molecules. The microcrystal-based immunoassay for the
      detection of M-IgG performed with microcrystals having antibody surface coverage
      of 5.05 mg m(-2) showed a sensitivity of 3.93 nA microg(-1) L(-1) with a
      detection limit of 2.82 microg L(-1).

PMID- 15859601
TI  - Optical sensors for the determination of concentrated hydroxide. Characterization
      of the sensor materials and evaluation of the sensor performance.
AB  - Optical sensors for the determination of highly concentrated bases such as NaOH
      (1-10 M) and materials to make these sensors have been characterized by X-ray
      photoelectron spectroscopy, 29Si solid-state NMR, FT-IR, and measurements of film
      porosity, surface area, and thickness. The bonding character and composition of
      the Si-Zr mixed oxides-organic polymer composites were evaluated. These studies
      suggest that there are Si-O-Zr matrixes in the mixed oxides, and that the Si-O-Zr
      matrixes contribute to the durability of the base sensors in highly alkaline
      solutions. The performance of these base sensors has been studied in detail as
      well. These sensors were stable for approximately 120 days, exhibited short
      response times (typically <10 s), and were fully reversible with minimal
      hysteresis effects in NaOH-ROH-H2O solutions (R = Me, Et, and i-Pr).

PMID- 15859602
TI  - Kinetic aspects of Donnan membrane technique for measuring free trace cation
      concentration.
AB  - Addition of ion complexation ligands in the acceptor solution in the Donnan
      membrane technique (DMT) can lower its detection limit for free metal ion
      concentration in natural samples. In this paper, the influence of added ligands
      on the transport behavior of trace ions in DMT was studied using numerical and
      analytical models and experimental tests. The results show that addition of
      ligands in the acceptor can significantly influence the time to reach the Donnan
      membrane equilibrium. Depending on several factors, the flux can be controlled by
      the diffusion in the stagnant solution film at the solution-membrane interface,
      by the diffusion in the membrane, or by both. The conditions under which the
      diffusion in the solution film or in the membrane becomes the rate-limiting step
      are discussed and approximate analytical solutions for some special cases are
      presented. Very low concentrations of free metal ion can be measured using the
      ligand complexation DMT. Depending on the degree of complexation in the sample,
      the measurement can be based on either the Donnan membrane equilibrium (when the
      complexation degree is low) or the kinetic interpretation of the ion transport
      (when the complexation degree is high).

PMID- 15859603
TI  - Detection of peroxidase/H2O2-mediated oxidation with enhanced yellow fluorescent
      protein.
AB  - The ability to sense oxidative stress in live cells and organisms would have far
      reaching implications for biotechnology, drug discovery, and potentially medical
      imaging. We hypothesized that tyrosine-containing fluorescent proteins could be
      used as switches for sensing oxidative stress, based on their sensitivity to
      environmental and structural variations. We therefore tested purified EGFP, EYFP,
      ECFP, and DsRed proteins against the heme-peroxidase/H(2)O(2) reaction. We found
      that peroxidase-mediated oxidation resulted in up to 99.5% quenching of EYFP
      fluorescence (but not that of other fluorescent proteins) in a dose-dependent
      manner. Western blotting revealed inter- and intramolecular cross-linking. The
      observed detection limit for hydrogen peroxide was approximately 100 nM, well
      below the extracellular levels previously reported to occur in mammalian tissue
      during signaling. Combined expression of EYFP (quenchable) and ECFP or EGFP
      (nonquenchable) is expected to allow sensitive monitoring of oxidative stress.

PMID- 15859604
TI  - Genosensor based on a platinum(II) complex as electrocatalytic label.
AB  - Voltammetric genosensors on streptavidin-modified screen-printed carbon
      electrodes (SPCEs) for the detection of virulence nucleic acid determinants of
      pneumolysin (ply) and autolysin (lytA) genes, exclusively present on the genome
      of the human pathogen Streptococcus pneumoniae, were described. The
      oligonucleotide probes were immobilized on electrochemically pretreated SPCEs
      through the streptavidin/biotin reaction. After that, the hybridization reaction
      was carried out with labeled complementary targets on the electrode surface. The
      ply and lytA targets were labeled using the universal linkage system, which
      consists of the use of a platinum(II) complex that acts as coupling agent between
      targets and a, usually fluorescent, molecule label. In this case, the
      platinum(II) complex acts as a label itself because the analytical signal is
      achieved by measuring chronoamperometrically the current generated by the
      hydrogen evolution catalyzed by platinum. In nonstringent experimental
      conditions, these genosensors can detect 24.5 fmol of 20-mer oligonucleotide
      target and discriminate between a complementary oligo and an oligo with a three
      base mismatch. In presence of 25% formamide in the hybridization buffer, a single
      base mismatch on the oligonucleotide target can be detected.

PMID- 15859605
TI  - Deconvolution of concentration recordings at live cell preparations via shape
      error optimization.
AB  - In many fields of science and engineering including several areas in analytical
      chemistry, deconvolution needs to be performed on measured data to extract
      meaningful information. This situation arises when a variable of interest has to
      be indirectly estimated from a measurable quantity that depends on this variable
      in some known manner. This dependence, called the "forward problem", has to be
      computationally undone to obtain the information sought from the experimental
      results. Solving this "inverse problem" requires deconvolution whenever the
      forward problem involves convolution. Despite its ubiquitous importance, however,
      performance of the methodologies used for deconvolution remains often
      unsatisfactory. An example is in bioanalytical applications where microsensing at
      live preparations is performed to obtain information on biological transport. It
      is in this context that a novel approach to solve inverse problems, shape error
      optimization, is proposed and tested in this work. The experimental paradigm
      addressed is in the area of multidrug resistance (MDR) in cancer that gives rise
      to passive and active drug efflux from cells. Doxorubicin (DOX) concentration is
      monitored with a carbon fiber microelectrode in vitro at close proximity to a
      monolayer of cells expressing MDR. The measured local concentration is the result
      of convolution of cellular efflux with the impulse response of diffusion in the
      extracellular medium. Hence, estimating DOX efflux, which is the biologically
      meaningful information, leads to a deconvolution problem. Performance of
      deconvolution via shape error optimization is compared with that of two
      conventional techniques: discrete Fourier transform and square error
      optimization. The results obtained are also applicable to other areas of science
      and engineering where deconvolution is commonly used for processing experimental
      data.

PMID- 15859606
TI  - Comparison of glycosphingolipids and antibodies as receptor molecules for ricin
      detection.
AB  - Glycosphingolipids (GSLs) have been shown to undergo strong interactions with a
      number of protein toxins, including potential bioterrorism agents such as ricin
      and botulinum neurotoxin. Characterization of this interaction in recent years
      has led to a number of studies where GSLs were used as the recognition molecules
      for biosensing applications. Here, we offer a comparison of quartz crystal
      microbalance (QCM) sensors for the detection of ricin using antibodies and the
      GSLs GM1 and asialoGM1, which have been shown to undergo strong interactions with
      ricin. The presence, orientation, and activity of the GSL and antibody films were
      confirmed using ellipsometry, Fourier transform infrared spectroscopy (FT-IR),
      and QCM. It was found that the GSLs offered more sensitive detection limits when
      directly compared with antibodies. Both GSLs had lower detection limits at 5
      microg/mL, approximately 5 times lower than were found for antibodies (25
      microg/mL), and their linear detection range extended to the highest
      concentrations tested (100 microg/mL), almost an order of magnitude beyond the
      saturation point for the antibody sensors. Potential sites for nonspecific
      adsorption were blocked using serum albumin without sacrificing toxin
      specificity.

PMID- 15859607
TI  - LC/MS/MS method for quantitative determination of long-chain fatty acyl-CoAs.
AB  - Long-chain acyl-CoA esters (LCACoAs) are activated lipid species that represent
      key substrates in lipid metabolism. The relationship between lipid metabolism
      disorders and type 2 diabetes has attracted much attention to this class of
      metabolites. This paper presents a highly sensitive and robust on-line LC/MS(2)
      procedure for quantitative determination of LCACoAs from rat liver. A fast SPE
      method has been developed without the need for time-consuming evaporation steps
      for sample preparation. LCACoAs were separated with high resolution using a C18
      reversed-phase column at high pH (10.5) with an ammonium hydroxide and
      acetonitrile gradient. Five LCACoAs (C16:0, C16:1, C18:0 C18:1, C18:2) were
      quantified by selective multireaction monitoring using a triple quadrupole mass
      spectrometer in positive electrospray ionization mode. It is possible to perform
      a neutral loss scan of 507 for lipid profiling of complex LCACoA mixtures in
      tissue extracts. The method presented was validated according to ICH guidelines
      for quantitative determination of five LCACoAs for physiological concentrations
      in 100-200 mg of tissue with accuracies ranging from 94.8 to 110.8%, interrun
      precisions between 2.6 and 12.2%, and intrarun precisions between 1.2 and 4.4%.
      Due to the high sensitivity of the developed method, the amount of tissue
      biopsied for reliable quantification can be reduced. This may be advantageous in
      the quantification of LCACoAs in humans.

PMID- 15859608
TI  - Classification of nerve cells from substantia nigra of patients with Parkinson's
      disease and amyotrophic lateral sclerosis with the use of X-ray fluorescence
      microscopy and multivariate methods.
AB  - The causes of Parkinson's disease and amyotrophic lateral sclerosis are still not
      known, but there is evidence that metal ions can be involved in processes leading
      to degeneration and atrophy of neurons in the case of these two neurodegenerative
      disorders. A synchrotron microbeam X-ray fluorescence technique was applied for
      topographic and quantitative analyses of selected elements on central nervous
      system tissue. The thin slices of brain were measured on the undulator beamline
      ID 22 at the European Synchrotron Radiation Facility in Grenoble, France. The
      polychromatic beam with the dimension of 5 microm x 2 microm (horizontal x
      vertical) was used in measurements. Tissues of substantia nigra representing
      Parkinson's disease, amyotrophic lateral sclerosis, and the control case were
      scanned. The results obtained indicated that accumulation of some elements
      depends on the case that the substantia nigra represents. Some variability in the
      elemental distribution for a given case was noticed as well. To investigate if
      present differences in the elemental accumulation between analyzed cases are
      statistically significant, multivariate methods were used. Cluster and
      discriminant analyses confirmed the significance of the differences in elemental
      accumulation in biological structures representing the examined cases. The
      methods used let us classify these structures in separate groups and determine
      elements, which play the greatest role in the differentiation of the biological
      structures for each case.

PMID- 15859609
TI  - Monitoring the mode of action of antibiotics using Raman spectroscopy:
      investigating subinhibitory effects of amikacin on Pseudomonas aeruginosa.
AB  - During the last 20 years the rate at which new antimicrobial agents are produced
      has decreased dramatically, with concomitant increase in the number of pathogens
      that are becoming multidrug resistant. Together these have created a patient
      healthcare risk and this is of great concern. A crucial aspect for the discovery
      of new antibiotics is the development of new techniques that allow rapid and
      accurate characterization of the mode of action of the pharmacophore. In this
      work UV resonance Raman (UVRR) spectroscopy has been developed to monitor the
      concentration effect of antibiotics on bacterial cells. UVRR was conducted at 244
      nm and spectra were collected in typically 60 s. Supervised multivariate analysis
      and 2D correlation spectroscopy were used to evaluate whether the UVRR spectra
      contained valuable information that could be used to study the mode of action of
      antibiotics. The clustering pattern in the discriminant factors space correlated
      directly to the concentration of amikacin, and partial least squares (PLS)
      regression analysis of the UVRR spectra was able to predict the concentration of
      amikacin to which bacterial cells had been exposed. 2D correlation spectroscopy
      contour maps indicated that spectral changes due to the presence of amikacin in
      the growth media occur according to the known mode of action of the studied
      antibiotic. Therefore, we conclude that UVRR spectroscopy, when coupled with
      chemometrics and 2D correlation spectroscopy, constitutes a powerful approach for
      the development and screening of new antibiotics.

PMID- 15859610
TI  - Microfluidics and chromatography with an atomic force microscope.
AB  - A combined atomic force microscope (AFM) and Raman spectrometer is presented as a
      microfluidic device for pumping, sampling, and trace chemical analysis. The AFM
      tip-cantilever provides a mechanism for shear-driven pumping of fluids in
      microchannels. Shear-driven pumping allows rapid flow rates and avoids the
      limitations of conventional pumping. The AFM's ability to translate sub
      femtoliter volumes of fluid also proves a mechanism for fluidic switching and
      sample injection. In addition, the AFM is used to image liquid surfaces in
      microchannels and remove samples for very sensitive spectral analysis. Surface
      enhanced Raman spectroscopy localized near the AFM tip provides chemical
      information of the sampled fluids. The results demonstrate the feasibility of
      integrating the AFM with microfluidic circuits and shear-driven chromatography
      and the potential for nanometer-scale chromatography.

PMID- 15859611
TI  - Identification and elimination of polysiloxane curing agent interference
      encountered in the quantification of low-picogram per milliliter methyl tert
      butyl ether in blood by solid-phase microextraction headspace analysis.
AB  - Widespread use of the gasoline additive methyl tert-butyl ether (MTBE) and the
      subsequent human exposure that follows have led to the need to quantify MTBE in a
      variety of complex biological matrixes. In this work, we demonstrate our latest
      MTBE quantification assay for whole blood and uncover previously unidentified
      contamination sources that prevented routine quantification in the low picogram
      per milliliter (parts per trillion, ppt) range despite a sensitive and selective
      analytical approach. The most significant and unexpected sources of contamination
      were found in reagents and laboratory materials most relevant to sample
      preparation and quantification. In particular, significant levels of MTBE were
      identified in sample vial septa that use poly(dimethylsiloxane) (PDMS)-based
      polymers synthesized with peroxide curing agents having tert-butyl side groups.
      We propose that MTBE is one of the byproducts of these curing agents, which cross
      link PDMS via the methyl side groups. Residual MTBE levels of approximately 20
      microg/septa are seen in septa whose formulations use these curing agents.
      Fortunately, these levels can be significantly reduced (i.e., <0.2 ng/septa) by
      additional processing. Performance achieved with this sample preparation approach
      is demonstrated using a mass spectrometry-based method to quantify blood MTBE
      levels in the low-ppt range.

PMID- 15859612
TI  - Use of DNA repair enzymes in electrochemical detection of damage to DNA bases in
      vitro and in cells.
AB  - Electrochemical measurements at mercury or solid amalgam electrodes offer a
      highly sensitive detection of DNA strand breaks. On the other hand,
      electrochemical detection of damage to DNA bases at any electrode is usually much
      less sensitive. In this paper, we propose a new voltammetric method for the
      detection of the DNA base damage based on enzymatic conversion of the damaged DNA
      bases to single-strand breaks (ssb), single-stranded (ss) DNA regions, or both.
      Supercoiled DNA exposed to UV light was specifically cleaved by T4 endonuclease
      V, an enzyme recognizing pyrimidine dimers, the major products of photochemical
      DNA damage. Apurinic sites (formed in dimethyl sulfate-modified DNA) were
      determined after treating the DNA with E. coli exonuclease III, an enzyme
      introducing ssb at the abasic sites and degrading one of the DNA strands. The ssb
      or ssDNA regions, or both, were detected by adsorptive transfer stripping
      alternating current voltammetry at the mercury electrode. This technique offers
      much better sensitivity and selectivity of DNA base damage detection than any
      other electrochemical method. It is not limited to DNA damage in vitro, but it
      can detect also DNA base damage induced in living bacterial cells.

PMID- 15859613
TI  - Atmospheric pressure ionization in a miniature mass spectrometer.
AB  - A miniature cylindrical ion trap mass spectrometer featuring an atmospheric
      pressure interface allowing atmospheric pressure chemical ionization and
      electrospray ionization is described together with its analytical performance
      characteristics. The vacuum system, ion optics, mass analyzer, control
      electronics system, and detection system have all been designed and built in
      house. The design is based upon a three-stage, differentially pumped vacuum
      system with the instrument capable of being interfaced to many types of
      atmospheric pressure ionization sources. Ions are transferred through home-built
      ion optics, and instrument control is achieved through custom-designed
      electronics and LabView control software. Corona discharge ionization and
      electrospray ionization sources are implemented and used to allow the analysis of
      both gaseous- and solution-phase samples during the characterization of the
      instrument. An upper mass/charge limit of approximately 450 Th with unit
      resolution was achieved using a 2.5-mm-internal radius cylindrical ion trap as
      the mass analyzer. The specificity of the instrument can be increased by
      employing the MS/MS capabilities of the ion trap and has been demonstrated for
      nitrobenzene. Limits of detection for the trace analysis in air of the chemical
      warfare agent simulant methyl salicylate (1.24 ppb) and for nitrobenzene (629
      pptr) are achieved. The dynamic range of the instrument is currently limited to
      approximately 2 orders of magnitude by saturation of the detection electronics.
      Isolation and collision-induced dissociation efficiencies in MS/MS experiments
      both greater than 50% are reported. Electrospray/nanospray data are presented on
      solutions including 100 microM (D,L)-arginine, 10 microM (-)-ephedrine, and 10
      microM lomefloxacin.

PMID- 15859614
TI  - Simultaneous analysis of multiple classes of antibiotics by ion trap LC/MS/MS for
      assessing surface water and groundwater contamination.
AB  - Solid-phase extraction (SPE) and liquid chromatography in combination with ion
      trap mass spectrometry (LC/MS/MS) conditions were optimized for the simultaneous
      analysis of 13 antibiotics belonging to multiple classes and caffeine in 3
      different water matrixes. The single-cartridge extraction step was developed
      using a reversed-phase cartridge, resulting in recoveries for the 14 compounds
      ranging from 71 to 119% with relative standard deviations of 16% or lower. The
      analytes were separated in one chromatographic run, and the SPE-LC/MS/MS
      detection limits ranged from 0.03 to 0.19 microg/L. The SPE procedure was
      validated in groundwater, surface water, and wastewater. The analysis of samples
      from each of the three water matrixes revealed clindamycin (1.1 microg/L) in
      surface water and multiple antibiotics in wastewater (0.10-1.3 microg/L). The use
      of identification points to unambiguously assign the identity of antibiotics in
      various water matrixes was applied to an ion trap data-dependent scanning method,
      which simultaneously collects full scan and full scan MS/MS data for the
      unequivocal identification of target analytes.

PMID- 15859615
TI  - Derivatization using dimethylamine for tandem mass spectrometric structure
      analysis of enzymatically and acidically depolymerized methyl cellulose.
AB  - Structure analysis of partially depolymerized methyl cellulose was performed by
      nanoelectrospray ionization tandem mass spectrometry (nano-ESI-MS/MS) and by
      matrix-assisted laser desorption/ionization tandem mass spectrometry (MALDI
      MS/MS). Dimethylamine (DMA) was used for the first time as a reducing end
      derivatization reagent for oligosaccharides. This is an attractive reagent since
      it could be easily removed from the reaction mixture. Most important it also
      introduces a basic functional group that increased the sensitivity in both MALDI
      and nano-ESI. Depolymerization was made in two ways: one by the cellulose
      selective endoglucanase 5A from Bacillus agaradhaerens (Ba Cel5A) and the other
      by trifluoroacetic acid. The DMA derivatives formed both protonated and sodiated
      molecules in nano-ESI and MALDI. Tandem MS of protonated molecules yielded
      predominantly Y fragments from which the distribution of the substituents in the
      oligomers could be measured. Fragments obtained in tandem MS of sodiated
      molecules provided information regarding the positions of the substituents within
      the anhydroglucose units (AGUs). It was found that Ba Cel5A could cleave
      glucosidic bonds also if the AGU on the reducing side of the bond was fully
      methylated. The combination of DMA derivatization and tandem MS was demonstrated
      as a tool for the characterization of endoglucanase selectivity.

PMID- 15859616
TI  - Stable and fluid ethylphosphocholine membranes in a poly(dimethylsiloxane)
      microsensor for toxin detection in flooded waters.
AB  - Highly stable and fluid supported bilayer membranes were fabricated by fusion of
      positively charged ethylphosphocholine (DOPC+) vesicles into
      poly(dimethylsiloxane) (PDMS) microchannels for immunosensing of cholera toxin
      (CT) in flooded waters. Compared to phosphatidylcholine (PC) layers in the
      microchannels, DOPC+ membranes show exceptionally strong resistance to air-dry
      damage, as demonstrated by fluorescence recovery after photobleaching (FRAP)
      measurements and protein adsorption studies. In FRAP experiments, the mobile
      fraction of PC membranes was found to decrease by 10% upon drying/rehydration and
      the lateral diffusion coefficient decreased from 2.2 to 1.6 microm(2)/s, whereas
      the mobile fraction and diffusion coefficient for DOPC+ membranes remain
      virtually unchanged during this process. Characterization by confocal microscopy
      reveals that only 1% of the DOPC+ membrane in the microchannels was removed by
      the drying/rehydration process, as compared to 11% for PC. Protein adsorption
      trends indicate that the charge of DOPC+ membranes allows for tuning of solution
      conditions to enable the desired protein-membrane interaction to predominate at
      the interface. A flow-based immunoassay for bacterial toxin was developed with 5%
      GM1/DOPC+ membranes in PDMS channels, and a detection limit of 250 amol for CT
      was obtained from the calibration curves. The assay was successfully applied to
      detection of CT spiked in water samples from the Santa Ana River, with nearly
      identical response and sensitivity.

PMID- 15859617
TI  - Qualitative and quantitative analyses of ginkgo terpene trilactones by liquid
      chromatography/sonic spray ionization ion trap mass spectrometry.
AB  - A liquid chromatography/sonic spray ionization mass spectrometry method (LC/SSI
      MS) was developed for qualitative and quantitative analyses of ginkgo terpene
      trilactones. Five ginkgo terpene trilactones were successfully protonated for
      qualitative and quantitative analyses under the study conditions. The typical ion
      adducts were identified as (M + H)+, (M + NH4)+, and (M + Na)+. The limits of
      detection were achieved between 2.5 and 10 ng with RSD of 0.173-4.82% and a
      linear range of 10-80 ng with R2 = 0.991-0.999. This method was used to identify
      and quantify ginkgo terpene trilactones in extractions of ginkgo biloba leaves
      obtained from three different extraction methods. This is the first completely
      validated LC/MS method for quantification of ginkgo terpene trilactones. The
      factors that contributed to reduce the errors of identification and
      quantification of ginkgo terpene trilactones are systematically reported, and the
      advantages and disadvantages of LC/MS method in quantitative analysis are also
      discussed.

PMID- 15859618
TI  - Quantitation of trace metals in liquid samples by dried-droplet laser ablation
      inductively coupled plasma mass spectrometry.
AB  - A new, discrete sample introduction approach based on laser ablation (LA) is
      described for the quantitation of several trace metals in aqueous samples by
      ICPMS. Dried microdroplets of sample, previously mixed with a sodium acetate
      matrix, were quantitatively ablated from a polystyrene substrate. Calibration via
      the method of standard additions or isotope dilution provided accurate results
      for Ni, Cd, and Pb in drinking water and Se in a yeast extract. Compared to
      conventional solution nebulization, LA sample introduction provided a 2-7-fold
      enhancement in absolute sensitivity and transport efficiency of 2-14% for the
      elements examined. Estimated detection limits are 1-7-fold poorer for the dried
      droplet LA technique, primarily a result of degraded precision arising from
      counting statistics limitations for discrete sample introduction. On the basis of
      the several-second half-width of the resulting transient signals, sample
      throughput can be in the range of 250 samples per hour. Additionally, integration
      of the transient signal should eliminate contributions to elemental fractionation
      from the LA step. Dried-droplet LA-ICPMS offers several advantages over its
      counterpart, ETV-ICPMS, with respect to background intensity, throughput, and
      ease of desorption.

PMID- 15859620
TI  - Determination of 16 phthalate metabolites in urine using automated sample
      preparation and on-line preconcentration/high-performance liquid
      chromatography/tandem mass spectrometry.
AB  - We developed an on-line solid-phase extraction (SPE) method, coupled with isotope
      dilution high-performance liquid chromatography/tandem mass spectrometry
      (HPLC/MS/MS) and with automated sample preparation, to simultaneously quantify 16
      phthalate metabolites in human urine. The method requires a silica-based
      monolithic column for the initial preconcentration of the phthalate metabolites
      from the urine and a silica-based conventional analytical column for the
      chromatographic separation of the analytes of interest. It uses small amounts of
      urine (100 microL), is sensitive (limits of detection range from 0.11 to 0.90
      ng/mL), accurate (spiked recoveries are approximately 100%), and precise (the
      inter- and intraday coefficients of variation are <10%). The method is not labor
      intensive, and, because pretreatment of the urine samples was performed
      automatically using an HPLC autosampler, involves minimal sample handling, thus
      minimizing exposure to hazardous chemicals. The method was validated on spiked,
      pooled urine samples and on urine samples from 43 adults with no known exposure
      to phthalates. The high sensitivity and high throughput (HPLC run time, including
      the preconcentration step, is 27 min) of this analytical method combined with the
      ease of use and effective automated sample preparation procedure make it suitable
      for large epidemiological studies to evaluate the prevalence of human exposure to
      phthalates.

PMID- 15859619
TI  - Concentration profiling in rat tissue by high-resolution magic-angle spinning NMR
      spectroscopy: investigation of a model drug.
AB  - The utility of high-resolution magic-angle spinning (HR-MAS) NMR for studying
      drug delivery in whole tissues was explored by dosing female Sprague-Dawley rats
      with topical or injectable benzoic acid (BA). In principle, HR-MAS NMR permits
      the detection of both intra- and extracellular compounds. This is an advantage
      over the previous detection of topically applied BA using microdialysis coupled
      to HPLC/UV as microdialysis samples only the extracellular space. Skin and muscle
      samples were analyzed by (1)H HR-MAS NMR, and BA levels were determined using an
      external standard solution added to the sample rotor. One to two percent of the
      BA topical dose was detected in the muscle, showing that BA penetrated through
      the dermal and subcutaneous layers. Since BA was not detected in the muscle in
      the microdialysis studies, the NMR spectra revealed the intracellular
      localization of BA. The amount of BA detected in muscle after subcutaneous
      injection correlated with the distance from the dosing site. Overall, the results
      suggest that HR-MAS NMR can distinguish differences in the local concentration of
      BA varying with tissue type, dosage method, and tissue proximity to the dosing
      site. The results illustrate the potential of this technique for quantitative
      analysis of drug delivery and distribution and the challenges to be addressed as
      the method is refined.

PMID- 15859621
TI  - Two-fold efficiency increase by selective excitation of ions for consecutive
      activation by ion-electron reactions and vibrational excitation in tandem fourier
      transform ion cyclotron resonance mass spectrometry.
AB  - A new technique called selective excitation of ions for consecutive activation
      (SEICA) is proposed for obtaining complementary fragmentation mass spectra from
      the same precursor ion population. SEICA utilizes precursor ions remaining intact
      after electron capture dissociation or another ion-electron reaction for
      efficient MS/MS based on a vibrational excitation (VE) technique, such as
      infrared multiphoton dissociation. SEICA uses the ability of ion-trapping
      instruments to detect product ions while retaining inside the trap intact
      precursor ions, making the latter available for consecutive activation by a VE
      technique. The possibility of practical implementation of SEICA by software-only
      modification of a commercial instrument is demonstrated. A 2-fold increase in the
      efficiency is achieved for both "single-scan" and "multiple-scan" experiments.
      This improvement can be particularly important for high-sensitivity applications
      in, for example, proteomics, where limited ECD efficiency poses an obstacle for
      broad implementation of this technique.

PMID- 15859622
TI  - Microchip HPLC of peptides and proteins.
AB  - Rapid microchip reversed-phase HPLC of peptides and proteins at pressure
      gradients of 12 bar/cm (180 psi/cm) has been performed using a microdevice that
      integrates subnanoliter on-chip injection and separation with a miniaturized
      fluorescence detector. Proteins and peptides were separated on a C18 side-chain
      porous polymer monolith defined by contact lithography, and injection was
      achieved via a pressure-switchable fluoropolymer valve defined using projection
      lithography. Preliminary separations of peptide standards and protein mixtures
      were performed in 40-200 s, and switching between samples with no detectible
      sample carryover has been performed. The injections and separations were
      reproducible; the relative standard deviation (RSD) for retention time was 0.03%,
      and peak area RSD was 3.8%. Sample volumes ranging from 220 to 800 pL could be
      linearly metered by controlling the pressure injection pulse duration with
      conventional timing and valving. The current prototype system shows the potential
      for rapid and autonomous HPLC separations with varying modalities and the
      potential for direct connection to mass spectrometers at nanospray flow rates.

PMID- 15859623
TI  - Determination of 25-hydroxyvitamin D in human plasma using high-performance
      liquid chromatography--tandem mass spectrometry.
AB  - We report here the development of a precise and sensitive method to determine 25
      hydroxyvitamin D (25-OH-D(2)/ -D(3)) in human plasma using high-performance
      liquid chromatography-tandem mass-mass spectrometry with atmospheric pressure
      chemical ionization (LC-APCI-MS/MS). The method involves the use of deuterated 25
      OH-D(3) as an internal standard compound for 25-OH-D(2)/-D(3), which was
      synthesized in our laboratory, and the selection of a precursor and product ion
      with a MS/MS multiple reaction monitoring method. The average intraassay and
      interassay variation values (relative standard deviation) were 5.7 and 2.5%,
      respectively, for 25-OH-D(3) and 4.5 and 5.1%, respectively, for 25-OH-D(2). The
      average spiked recoveries from authentic compounds added to normal human plasma
      samples for 25-OH-D(3) and 25-OH-D(2) were 103.8 and 98.8%, respectively. Mean
      plasma concentrations of 25-OH-D(3) and 25-OH-D(2) in healthy subjects were 20.5
      and 0.4 ng/mL, respectively. We conclude that this novel LC-APCI-MS/MS method
      would be useful for the evaluation of the vitamin D status in postmenopausal
      women and elderly subjects and provide useful information in the diagnosis of
      vitamin D insufficiency/deficiency, as well as for the treatment and prevention
      of osteoporosis with vitamin D.

PMID- 15859624
TI  - Interface for direct and continuous sample-matrix deposition onto a MALDI probe
      for polymer analysis by thermal field flow fractionation and off-line MALDI-MS.
AB  - A simple interface based on an oscillating capillary nebulizer (OCN) is described
      for direct deposition of eluate from a thermal field-flow fractionation (ThFFF)
      system onto a matrix-assisted laser desorption/ionization (MALDI) probe. In this
      study, the polymer-containing eluent from the ThFFF system was mixed on-line with
      MALDI matrix solution and deposited directly onto a moving MALDI probe. The
      result was a continuous sample track representative of the fractionation process.
      Subsequent off-line MALDI-mass spectrometry analysis was performed in automated
      and manual modes. Polystyrene samples of broad polydispersity were used to
      characterize the overall system performance. The OCN interface is easy to build
      and operate without the use of heaters or high voltages and is compatible with
      any MALDI probe format.

PMID- 15859625
TI  - Fabrication of ultramicroelectrodes using a "teflon-like" coating material.
AB  - A new method was developed for the preparation of ultramicroelectrodes (UMEs). In
      this method, a photo-curable fluorinated functionalized perfluoropolyether, a
      liquid v-like polymer at room temperature, is used as the material for the
      insulation of metal microwires or carbon fibers. The UMEs prepared by this method
      were usually conical shaped and could be used both in aqueous solutions and with
      aprotic solvents. The relatively small thicknesses of the insulating sheath of
      the "Teflon-like"UME tips make them particularly useful for scanning
      electrochemical microscopy measurements.

PMID- 15859626
TI  - Chemically modified glass fiber as a matrix-free reference material for volatile
      compounds.
AB  - Difficulties with obtaining suitable reference materials, which are applied for
      validation of analytical procedures and calibration of measured devices used in
      gaseous examinations (atmospheric air, indoor air, workplace atmosphere), are one
      of the most important challenges that stand in front of analytics. Known gaseous
      standard mixtures preparation techniques, both static and dynamic, are burdened
      with lots of inconveniences and disadvantages, which can be responsible for false
      analytical results. It appears that a very important step in the way of obtaining
      suitable reference materials useful in gaseous analysis is the technique of
      thermal decomposition of surface compounds. The paper describes a new type of
      matrix-free reference material-chemically modified glass fiber, which
      significantly makes it easier and simplifies the usage of reference materials
      produced using this technique.

PMID- 15859627
TI  - Soft tissue amyloidomas of the extremities.

PMID- 15859628
TI  - How expert are the experts? Implications for proficiency testing in
      cervicovaginal cytology.

PMID- 15859630
TI  - Measuring the significance of field validation in the College of American
      Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology: how
      good are the experts?
AB  - CONTEXT: Expert opinion is often used as a gold standard for gynecologic cytology
      in the evaluation of new technologies, in the legal setting, and in the
      validation of cases for use in educational programs and proficiency testing.
      However, the reliability of expert opinion alone in selecting slides of a
      specific cytodiagnosis that can be reproducibly and reliably identified by
      subsequent reviewers has not been determined. OBJECTIVE: To assess the ability of
      expert opinion to select slides that are validated in subsequent reviews. DESIGN:
      In the College of American Pathologists Interlaboratory Comparison Program in
      Cervicovaginal Cytology, each case in every cytodiagnostic category is accepted
      for circulation only after review by 3 expert cytopathologists. The percentage of
      these cases that could not be reliably and reproducibly identified by program
      participants for each cytodiagnostic category ("failed field validation") was
      determined during the duration of the program from 1989 to 2004. RESULTS: More
      than 10,000 conventional smears and ThinPrep cases were selected by the expert
      panel for circulation. Of these selected slides, 19% of conventional smears and
      15% of ThinPrep specimens failed field validation. Compared with the overall
      slide performance, significantly higher percentages (P < .001) of conventional
      smears with reference diagnoses of unsatisfactory (51.7%), repair (58%), or low
      grade intraepithelial lesion (31.8%) and of ThinPrep specimens with reference
      diagnoses of unsatisfactory (54.5%) and repair (76.9%) failed field validation.
      In contrast, significantly lower percentages of conventional smears with
      reference diagnoses of squamous cell carcinoma (4.5%), high-grade squamous
      intraepithelial lesion (9%), Trichomonas vaginalis infection (11.7%), or herpes
      (9.9%) and of ThinPrep specimens with reference diagnoses of adenocarcinoma
      (5.1%), herpes (2.1%), and fungal organism consistent with Candida (8.4%) failed
      field validation (P < .001 for all). CONCLUSIONS: Between 15% and 19% of
      gynecologic cytologic cases that have been selected by expert cytopathologists as
      good examples of cytodiagnostic abnormalities fail field validation. The
      proportion of cases failing field validation varies with cytodiagnostic category,
      but it occurs in all cytodiagnostic entities.

PMID- 15859631
TI  - Distinguishing carcinoid tumor from small cell carcinoma of the lung: correlating
      cytologic features and performance in the College of American Pathologists Non
      Gynecologic Cytology Program.
AB  - CONTEXT: The cytologic features of carcinoid tumor of the lung are well
      described. Nevertheless, some carcinoids may be difficult to distinguish from
      small cell carcinomas. OBJECTIVE: To correlate the cytologic features of
      individual cases of carcinoid tumor of the lung in fine-needle aspiration
      specimens in the College of American Pathologists Non-Gynecologic Cytology
      Program with the frequency of misclassification as small cell carcinoma. DESIGN:
      We reviewed 1100 interpretations from 26 different cases of carcinoid tumor in
      lung fine-needle aspiration specimens in the College of American Pathologists Non
      Gynecologic Cytology Program and correlated the cytologic features with the
      performance in the program. RESULTS: Cases were divided into those that were
      frequently misclassified as small cell carcinoma (at least 20% of the responses,
      19 cases) and those that were infrequently misclassified as small cell carcinoma
      (<10% of all responses, 7 cases). All cases had areas with classic features of
      carcinoid tumor. Cases were reviewed independently by 3 cytopathologists
      specifically looking for cytologic features that might be responsible for
      misclassification as small cell carcinoma. All 7 cases that were infrequently
      misclassified consisted of numerous monotonous well-preserved tumor cells that
      were either entirely round or were a mixture of round and spindle-shaped cells.
      Six of 7 cases showed a prominent streaming vascular pattern with tumor cells
      attached to the endothelial cell core. In contrast, cases that were frequently
      misclassified had 1 of 6 patterns that were not seen in cases that were rarely
      misclassified. These 6 patterns were: (1) poorly preserved and pale-staining
      cells with fine chromatin and a suggestion of molding (5 cases); (2) numerous
      large, well-preserved, spindle-shaped cells (2 cases); (3) numerous cells varying
      markedly in both size and shape (both round and spindle-shaped cells), with a
      common finding of degenerated, smudgy, small round and spindle-shaped cells (9
      cases); (4) hypocellular specimens (8 cases); (5) obscuration of cells by blood
      (2 cases); and (6) tumor cells present predominantly in groups, with few isolated
      cells (8 cases). In none of these cases were mitoses or true necrosis identified.
      CONCLUSIONS: Frequent misclassification of carcinoid tumor as small cell
      carcinoma in lung fine-needle aspiration specimens in this program correlates
      strongly with specific cytologic features, some of which are common in small cell
      carcinoma (fine chromatin, molding, smudgy chromatin) and others that are not
      (spindle-shaped cells). In addition, hypocellular specimens or specimens with
      cellular obscuration performed poorly, along with specimens exhibiting absence of
      the commonly described carcinoid feature of streaming vascularity. Awareness of
      these patterns may aid in avoiding misdiagnosis.

PMID- 15859632
TI  - Distinguishing small cell carcinoma from non-small cell carcinoma of the lung:
      correlating cytologic features and performance in the College of American
      Pathologists Non-Gynecologic Cytology Program.
AB  - CONTEXT: The cytologic features of small cell carcinoma of the lung are well
      described. Nevertheless, some small cell carcinomas may be difficult to
      reproducibly distinguish from non-small cell carcinomas, and this distinction
      carries significant clinical importance. OBJECTIVE: To correlate the cytologic
      features of individual cases of small cell carcinoma of the lung in fine-needle
      aspiration specimens from the College of American Pathologists Non-Gynecologic
      Peer Comparison Cytology Program with the frequency of misclassification as non-
      small cell carcinoma. DESIGN: We reviewed 1185 interpretations of 23 different
      cases of small cell carcinoma in lung fine-needle aspiration specimens and
      correlated the cytologic features noted in these cases with performance in the
      program. RESULTS: Cases were divided into those that were frequently
      misclassified as non-small cell carcinoma (at least 10% of the responses, 11
      cases) and those that were infrequently misclassified as non-small cell carcinoma
      (<5% of all responses, 12 cases). All cases had areas on the slides with classic
      features of small cell carcinoma. However, 10 of 11 cases that were frequently
      misclassified as non-small cell carcinoma had cells with either increased
      cytoplasm (4 cases), cytoplasmic globules (so-called paranuclear blue bodies) (3
      cases), or apparent intracytoplasmic lumina (3 cases). These features were not
      identified in cases that were infrequently misclassified (P = .005). In addition,
      cases more frequently misclassified as non-small cell carcinoma tended to show
      better overall cellular and group preservation. CONCLUSIONS: Frequent
      misclassification of small cell carcinoma as non-small cell carcinoma in lung
      fine-needle aspiration specimens in this program correlates strongly with the
      presence of cytoplasmic features that may suggest non-small cell carcinoma or
      with the presence of paranuclear blue bodies. Misclassification in this program
      may reflect a variety of factors, including the variation in the cytologic
      features of individual cases, but also the lack of wide recognition that some
      features of non-small cell carcinoma may also be noted in well-preserved cases of
      small cell carcinoma.

PMID- 15859633
TI  - Glioblastomas in the older old.
AB  - CONTEXT: Recent studies have identified fundamental biological differences in the
      effects of epidermal growth factor receptor (EGFR) amplification on survival in
      older versus younger patients with glioblastoma multiforme (GBM). Cell cycle
      labeling indices have also been found to be inordinately high in older GBM
      patients and may contribute to the known adverse prognosis in this cohort.
      However, testing has not been conducted on significant numbers of patients of
      very advanced age, in whom these features might be expected to emerge as even
      more significant factors. OBJECTIVE: To assess EGFR amplification status and MIB
      1 indices in patients with GBM who are older than 75 years. DESIGN: We identified
      20 patients (female-male ratio, 11:9; 11 aged 75-79 years and 9 aged 80-87 years)
      and studied tumor tissue samples with immunohistochemistry for cell cycle
      labeling index and by fluorescence in situ hybridization for EGFR amplification.
      Survival data were obtained from the Colorado Tumor Registry. RESULTS: Mean MIB-1
      index was high (24.8%), but individual indices did not correlate with survival.
      EGFR amplification was detected in 25% of cases, with gain of chromosome 7 in all
      but one of the remaining patients. Ninety-five percent of patients manifested
      EGFR amplification and/or polysomy of chromosome 7. Heterogeneity was found
      within a given tumor, with 10% to 60% of cells showing gain of chromosome 7.
      Overall patient survival was poor (mean, 4.6 months), but was significantly
      longer in those with EGFR gene amplification (mean, 8.3 months; median, 10.5
      months) versus those without (mean, 3.2 months; median, 2.0 months) (P = .04).
      CONCLUSION: The presence of EGFR amplification is a significant predictor of
      survival time in older old patients.

PMID- 15859634
TI  - Stillbirths with placental hemorrhagic endovasculitis: a morphologic assessment
      with clinical implications.
AB  - CONTEXT: Hemorrhagic endovasculitis (HEV) is a vasodisruptive alteration
      affecting fetal-placental blood vessels of all calibers. Hemorrhagic
      endovasculitis is found in association with stillbirth and abnormalities of
      growth and development in livebirths. The role of HEV in the pathogenesis of
      these conditions is not known. OBJECTIVE: To further understand these events, we
      compare clinicopathologic features of HEV-affected placentas from stillbirths
      with those from livebirth pregnancies. Additionally, we assess the relationship
      of morphologic forms of HEV to clinical events and time of fetal death in utero
      and evaluate the significance of extensive versus localized HEV lesions in
      placentas of stillbirths. DESIGN: We reviewed the clinical records and slides
      from 119 stillbirths with placentas affected by HEV classified above a specified
      severity level (cases) and 119 matched stillbirths with placentas not affected by
      HEV (controls). A subset of 21 stillbirth placentas exhibiting focal HEV lesions
      was similarly evaluated. Slides were graded for HEV, villitis of unknown
      etiology, chorionic thrombi, villous fibrosis, erythroblastosis, and lesions
      indicative of maternal hypertension. Hemorrhagic endovasculitis was
      subcategorized into active, bland, and healed forms and clustered capillary
      lesions (hemorrhagic villitis). Focal, segmental, and diffuse patterns of villous
      fibrosis were delineated. Interlesional relationships were established by
      matching HEV severity indices with severity indices of co-existing lesions.
      Timing of fetal death was determined by published criteria. Data were analyzed
      for significance using chi2 and t tests. Results were compared with published
      analyses of livebirths with placental HEV. RESULTS: Lesions occurring with
      significant frequency in HEV-affected (case) placentas include villitis of
      unknown etiology, chorionic thrombi, villous fibrosis, erythroblastosis, and
      meconium staining. Interlesional relationships were evident between HEV and
      villous fibrosis, villitis of unknown etiology, and chorionic thrombi. Growth
      restriction was more common in case versus control infants (P = .02). A segmental
      pattern of villous fibrosis predominated in cases versus controls and within the
      case group (P < .001). Time to delivery after fetal death was longer in cases
      than controls. Active-vasodestructive forms of HEV correlate with shorter
      intervals of intrauterine retention, whereas bland forms correlate with longer
      intervals (P = .04). Placentas with focal HEV were associated with coexisting
      chorionic thrombi and villous fibrosis but not with fetal growth restriction.
      CONCLUSIONS: Patterns of interlesional interplay are similar in HEV-affected
      placentas of livebirths and stillbirths. This suggests that the pathogenesis of
      infant morbidity and mortality is similar in both groups. Active-vasodestructive
      forms of HEV may precede whereas bland forms may follow intrauterine demise. The
      segmental pattern of villous fibrosis and high incidences of growth restriction,
      erythroblastosis, and meconium in cases suggests a chronicity of adverse
      intrauterine events that may precede fetal loss. Stillbirths with focal HEV
      lesions are probably not at risk.

PMID- 15859636
TI  - Automatic 3-dimensional visualization of peripheral blood slides: a new approach
      for the detection of infection/inflammation at the point of care.
AB  - CONTEXT: The identification and quantitation of the intensity of the acute-phase
      response at the point of care might be of clinical relevance. OBJECTIVE: To
      report the possibility of automatic screening of unstained peripheral blood
      slides by using a 3-dimensional image analysis system. DESIGN: Peripheral venous
      blood was obtained from children with acute inflammation/infection and examined
      by an automatic 3-dimensional image analyzer to detect the number of white blood
      cells as well as to reveal the degree of erythrocyte aggregation, a marker of the
      humoral phase response. RESULTS: We included 66 children with acute bacterial
      infections and 59 with nonbacterial inflammation/infection; mean ages of the 2
      groups were 4.3 +/- 3.9 years and 4.2 +/- 3.7 years, respectively (P = .91). The
      percentages of correct classifications based on discriminant analysis in
      predicting between bacterial and nonbacterial inflammation/infection were 61.3%
      by using the white blood cell count, 64.5% by using the percentage of
      granulocytes, 61.6% by using the degree of erythrocyte aggregation, and 59.2% by
      using the number of leukocytes counted on the unstained slides. The results of
      the receiver-operated characteristic curve analysis yielded an area under the
      curve of 0.714 (P < .001) for the number of granulocytes, 0.699 (P < .001) for
      the white blood cell count, 0.685 (P < .001) for the number of leukocytes on the
      slides, and 0.685 (P = .001) for the degree of erythrocyte aggregation. The
      correlation between the number of leukocytes by the electronic cell analyzer and
      the number of cells counted on the slides was highly significant (r = 0.85, P <
      .001). CONCLUSIONS: It is feasible to use an automatic 3-dimensional image
      analyzer to reveal the different intensities of the acute-phase response between
      a group of children with an acute bacterial infection and another with
      nonbacterial inflammation/infection. These findings might be relevant for
      potential application at the point of care.

PMID- 15859635
TI  - Vascular invasion and herniation by hepatocellular carcinoma in cirrhosis: A wolf
      in sheep's clothing?
AB  - CONTEXT: Vascular invasion is an important diagnostic and prognostic feature of
      hepatocellular carcinoma (HCC) in cirrhosis. Intravascular free-floating tumor
      clusters (IvCs) of HCC are found histologically in the vicinity of HCC. Thrombus
      formation is not seen morphologically in association with these IvCs, which are
      usually covered by endothelium. OBJECTIVE: Our hypothesis is that these IvCs are
      the result of a nondestructive form of vascular invasion by HCC, and we tried to
      define this aspect of microvascular invasion more accurately. DESIGN: Tissue
      sections were stained with hematoxylin-eosin, and consecutive sections were
      stained for fibrin (Martius scarlet blue, fibrinogen), platelets (factor XIIIa),
      smooth muscle actin, and endothelium (CD34). We studied cirrhotic livers removed
      at transplantation between 1997 and 1999. Of the livers studied, 35 of 81
      consecutive cirrhotic livers contained HCC, and 17 showed microscopic vascular
      invasion. Five of these 17 cases showed IvCs and were subjected to the study.
      MAIN OUTCOME MEASURE: Presence or absence of thrombus formation in association
      with IvC. RESULTS: Usually, IvCs were covered by endothelium, and no associated
      thrombus formation was seen. In 1 case of HCC, thrombus formation was seen
      focally in association with disruption of the endothelial coating. CONCLUSIONS:
      We propose that the endothelial-lined trabecular structure of HCC everts,
      frondlike, via vascular structures within the tumor capsule into peritumoral
      vascular lumens without destruction of the endothelial coating. This may protect
      these HCC tumor projections from thrombus formation but may also act as a barrier
      to tumor extravasation, and this may be exploited from a therapeutic point of
      view.

PMID- 15859637
TI  - Immunohistochemical detection of glucose transporter GLUT1 in benign and
      malignant fallopian tube epithelia, with comparison to ovarian carcinomas.
AB  - CONTEXT: Enhanced expression of GLUT1, a facilitative glucose transporter found
      on red blood cells, blood-brain barrier, and perineurium, has been described in a
      large spectrum of epithelial malignancies. OBJECTIVE: We present an
      immunohistochemical survey of GLUT1 expression in benign and malignant fallopian
      tube epithelia, and compare serous carcinomas of the fallopian tube and ovary.
      DESIGN: One hundred two routinely fixed and processed archival specimens (36
      benign fallopian tubes, 29 primary tubal adenocarcinomas, and 37 primary ovarian
      adenocarcinomas) were immunostained with rabbit anti-GLUT1 and developed with
      streptavidin-biotin/diaminobenzidine. Only distinct membrane staining was scored
      positively (1+ to 3+). RESULTS: Benign tubes (n = 36) were either negatively
      stained (58.3%) or displayed rare weak staining (0.5+ to 1+, rarely 2+; 41.7%);
      of the latter, 4 specimens showed chronic salpingitis, and 6 showed hyperplasia
      (epithelial tufting and stratification). A case of florid hyperplasia with atypia
      in a BRCA1-positive patient was GLUT1 negative. Twenty-three (79.3%) of 29 tubal
      carcinomas were positively stained. Staining ranged from focal/scattered foci (n
      = 15) to multifocal/extensive (n = 8). Of the 6 nonstaining tubal carcinomas, 3
      were undifferentiated. Nineteen tubal carcinoma sections showed residual benign
      epithelium, which was consistently nonstaining. Very frequently, GLUT1 staining
      intensified in cells furthest from stroma/ stromal capillaries and/or bordering
      necrotic zones. On average, GLUT1 staining in primary fallopian tube cancers was
      less extensive than in primary ovarian adenocarcinomas. CONCLUSIONS: GLUT1
      immunostaining of fallopian tube adenocarcinomas was substantially stronger and
      more extensive than staining of benign tubal epithelium, consistent with
      previously described findings in carcinomas versus benign tissues from many
      primary sites. The frequent localization of GLUT1 positivity to regions most
      distal from stroma/stromal capillaries is consistent with known activation of
      GLUT1 expression by hypoxia-sensing cellular pathways and may constitute a
      survival advantage under hypoxic conditions present in malignancy. The difference
      in extent of GLUT1 staining between primary tubal and primary ovarian serous
      adenocarcinomas is discussed.

PMID- 15859638
TI  - Hematologic malignancies with primary retroperitoneal presentation:
      clinicopathologic study of 32 cases.
AB  - CONTEXT: The retroperitoneum is an uncommon location for primary lymphomatous
      involvement. Initial presentation of disease in this site (primary
      retroperitoneal lymphoma) is considered to be rare. Because of the uncommon
      anatomic location, the diagnosis and subsequent management of these patients tend
      to be difficult for both pathologists and clinicians. OBJECTIVE: This report
      describes our experience during a period of 6 years 4 months with patients with
      hematologic malignancies primarily presenting in the retroperitoneum. DESIGN: A
      retrospective search of our medical records generated 32 patients who presented
      initially with abdominal pain or discomfort as their predominant symptom and who
      were found by imaging studies to have retroperitoneal mass or masses. All the
      histopathology slides were reviewed and classified based on the World Health
      Organization classification. RESULTS: There were 13 male and 19 female patients.
      Tumor types included diffuse large B-cell lymphoma (n = 12); grade 1 follicular
      lymphoma (n = 4); grade 3 follicular lymphoma (n = 1); B chronic lymphocytic
      leukemia/small lymphocytic lymphoma (n = 2); multiple myeloma (n = 1); mixed
      cellularity Hodgkin lymphoma (n = 1); nodular sclerosis Hodgkin lymphoma (n = 1);
      aggressive B-cell lymphoma (n = 4); low-grade B-cell lymphoma (n = 4);
      lymphoblastic lymphoma, null cell type (n = 1); and precursor B-lymphoblastic
      lymphoma/leukemia (n = 1). More than half of the cases (17/32) were diagnosed on
      needle biopsy with immunophenotyping. CONCLUSIONS: Although open lymph node
      biopsy is a preferred method for diagnosis, needle biopsy plays a significant
      role in this setting, and, coupled with other information such as flow cytometry
      and immunohistochemistry, it is considered a practical and reliable method.

PMID- 15859639
TI  - A fast and simple high-performance liquid chromatography/mass spectrometry method
      for simultaneous measurement of whole blood tacrolimus and sirolimus.
AB  - CONTEXT: Combined immunosuppressant therapy using tacrolimus and sirolimus has
      demonstrable benefits. Simultaneous chromatographic monitoring of whole blood
      tacrolimus and sirolimus is useful for reducing reagent consumption and
      turnaround time. We report here a simple and rapid method using high-performance
      liquid chromatography/mass spectrometry for simultaneous measurement of whole
      blood tacrolimus and sirolimus. OBJECTIVE: To develop and validate a high
      performance liquid chromatography/mass spectrometry method that is suitable for
      clinical laboratories and that is simple, rapid, and cost-effective. DESIGN:
      Whole blood (80 microL) was mixed with zinc sulfate solution, followed by protein
      precipitation with acetonitrile containing the internal standards. After brief
      centrifugation, the supernatant (20 microL) was injected onto a C18 guard column.
      The drug and the internal standard ammonium adducts were monitored by multiple
      reaction monitoring. One-point calibration at levels of 200 ng/mL (249 nM)
      tacrolimus and 100 ng/mL (109 nM) sirolimus was prepared by adding tacrolimus and
      sirolimus to immunosuppressant-free whole blood. RESULTS: The assay took 2.5
      minutes per sample injection. The total imprecision was between 2.46% and 7.04%
      for tacrolimus and between 5.22% and 8.30% for sirolimus across the
      concentrations tested. No carryover was observed, and recoveries were 92% to 98%
      for tacrolimus and 100% for sirolimus at all levels tested. The tacrolimus was
      linear from 0.52 to 155.5 ng/mL (0.65-193.4 nM), and sirolimus was linear from
      0.47 to 94.8 ng/mL (0.51-103.7 nM). Biases of correlations with commercial
      methods were within 7%. CONCLUSIONS: This improved method is simple, fast, cost
      effective, and suitable for clinical laboratories. It has been implemented for
      routine clinical monitoring of posttransplantation immunosuppressant therapy.

PMID- 15859640
TI  - Addressing the maintenance of certification challenge: the College of American
      Pathologists response.
AB  - CONTEXT: The American Board of Medical Specialties Maintenance of Certification
      (MOC) process will become effective in 2006. The College of American Pathologists
      (CAP) Education Committee defined pathology-specific competencies within MOC
      categories and used data from a survey of pathologists to create education
      courses targeted to each MOC category. OBJECTIVE: To define pathology-specific
      competencies within MOC categories and to identify priority learning needs for
      pathologists. DESIGN: A 5-step process was completed for defining pathology
      specific competencies within MOC categories and creating education courses
      targeted to competencies identified in each MOC category. A random survey was
      distributed to identify priority learning needs based on the gap between the
      importance rating of each knowledge and skill statement and a rating of current
      level of proficiency in 3 areas. RESULTS: Specific competencies and knowledge and
      skill statements were identified for each MOC competency category. Findings
      indicate pathologists believe they are poorly prepared for practice in competency
      categories related to systems-based practice and practice-based learning and
      improvement. CONCLUSIONS: The CAP has focused education efforts on identifying a
      process for defining and responding to the MOC challenge. Pathologists have told
      us that they have significant needs for learning in specified areas and the CAP
      will focus development of education courses to meet those identified needs.

PMID- 15859641
TI  - Atypical angiomyolipoma of kidney in a patient with tuberous sclerosis: a case
      report with p53 gene mutation analysis.
AB  - Angiomyolipoma (AML) is the most common benign mesenchymal tumor of the kidney.
      It belongs to the family of perivascular epithelioid cell tumors and is typically
      composed of blood vessels, adipose tissue, and smooth muscle- like cells, which
      are characteristically positive for HMB-45. Results of recent studies suggest
      that p53 mutation may play an important role in AML progression. Here, we
      describe a locally destructive renal AML in a patient with tuberous sclerosis.
      The tumor consisted of mostly epithelioid cells with marked nuclear pleomorphism
      and frequent mitoses and was positive for HMB-45. The diagnosis of atypical
      epithelioid AML was made. Codon alteration in the p53 gene was not detected,
      despite focal p53 immunoreactivity and single nucleotide polymorphism at exon 6.
      Our finding indicates no definite link between p53 abnormalities and the atypical
      appearance of AML. To the best of our knowledge, this is the second renal AML
      case investigated for p53 mutations.

PMID- 15859642
TI  - Ellis-van Creveld syndrome and dyserythropoiesis.
AB  - Ellis-van Creveld (EVC) syndrome or chondroectodermal dysplasia is a rare
      autosomal recessive disorder characterized by a variable spectrum of clinical
      findings. Classical EVC syndrome comprises a tetrad of clinical manifestations of
      chondrodystrophy, polydactyly, ectodermal dysplasia, and cardiac defects. In
      several case reports, dysplasia involving other organs has also been identified.
      Hematologic abnormalities have been rarely reported in patients with EVC
      syndrome. Here, we report a case of a 3-year-old Hispanic boy with EVC syndrome
      and marked dyserythropoiesis. The dyserythropoiesis may be part of an isolated
      myelodysplastic change or a primary myelodysplastic syndrome and likely
      represents an unusual EVC syndrome association. To our knowledge, this
      association has not been previously reported.

PMID- 15859643
TI  - Pleomorphic giant cell carcinoma of the prostate.
AB  - We report the clinical and pathologic features of 2 cases of pleomorphic giant
      cell carcinoma of the prostate. One case was found at autopsy in a 77-year-old
      man and was composed of high-grade prostatic adenocarcinoma with prominent
      anaplastic giant cells. The patient presented with metastases to multiple
      retroperitoneal lymph nodes, liver, and lumbar vertebrae. The second case
      occurred in a 45-year-old man who underwent transurethral resection of the
      prostate and was found to have high-grade prostatic adenocarcinoma with an
      extensive anaplastic giant cell component. The patient presented with distant
      metastases and died within 9 months. Both regular adenocarcinoma and anaplastic
      giant tumor cells displayed cytoplasmic immunoreactivity for prostate-specific
      antigen, prostatic acid phosphatase, and keratin AE1/AE3; in one case, scattered
      cells were also positive for chromogranin and epithelial membrane antigen.
      Pleomorphic giant cell carcinoma is a rare variant of prostatic adenocarcinoma
      with a poor prognosis that should be considered in the differential diagnosis of
      prostatic pleomorphic tumors.

PMID- 15859644
TI  - Swyer-James (MacLeod) syndrome with placental transmogrification of the lung: a
      case report and review of the literature.
AB  - Swyer-James (MacLeod) syndrome is an acquired form of unilateral hyperlucency of
      the lung and is characterized by the development of severe emphysema,
      bronchiectasis, and/or bronchiolitis obliterans. It may develop as a complication
      of repeated episodes of pulmonary infection resulting in bronchiolitis obliterans
      and obstruction of small airways. Most patients with Swyer-James (MacLeod)
      syndrome can be managed clinically, and the pathologic features of the syndrome
      have been described in only a few reports. Placental transmogrification of the
      lung is a rare histopathologic finding that has been described in patients with
      severe emphysema associated with cigarette smoking, congenital bullous emphysema,
      and fibrochondromatous hamartomas of the lung and is characterized by the
      development of peculiar structures in the pulmonary parenchyma that resemble
      placental villi. To our knowledge, placental transmogrification of the lung has
      not been previously described in patients with Swyer-James (MacLeod) syndrome. We
      encountered a 32-year-old man with a history of childhood asthma who presented
      with progressively severe exertional dyspnea and had unilateral right lung
      hyperlucency. The patient underwent a right pneumonectomy. Examination of the
      lung revealed severe mixed centriacinar-panacinar emphysema in all lobes, bullous
      emphysema in the upper lobe, bronchiectases, mild interstitial pneumonia with
      fibrosis, and placental transmogrification of the pulmonary parenchyma of all 3
      lobes. Here, we review the pathology of Swyer-James (MacLeod) syndrome and the
      possible pathogenesis of villous-like changes in the lung tissues.

PMID- 15859645
TI  - Perivascular epithelioid cell tumor of the oral mucosa.
AB  - Perivascular epithelioid cell tumors (PEComas) are a family of tumors defined by
      the coexpression of melanocytic and muscle markers. Examples have been reported
      in many organs, soft tissues, and bone. Further expanding the list of locations,
      we report a case arising in the hard palate. Histologically, the tumor was
      composed of large elongated or epithelioid cells with granular cytoplasm.
      Immunohistochemically, tumor cells were positive for HMB-45, Melan A/MART-1,
      CD10, smooth muscle actin, desmin, and calponin. Ultrastructural examination
      revealed stage I melanosomes, thin filaments, and dense plaques. Recurrence has
      not been reported after 20 months. To our knowledge, this is the first detailed
      description of an intraoral PEComa.

PMID- 15859646
TI  - Primary breast lymphoma cytologic diagnosis.
AB  - Primary non-Hodgkin lymphoma of the breast is a rare pathology, and bilateral
      involvement is exceptional. We report a case of bilateral primary non-Hodgkin
      lymphoma of the breast in a 40-year-old woman. Predominantly atypical lymphocytes
      and rare plasma cells were found in the microscopic evaluation of the fine-needle
      aspiration biopsy of the right and left breasts. Microscopic findings of the
      incisional biopsy of the left breast were in accordance with non-Hodgkin diffuse
      large B-cell lymphoma. The patient received systemic chemotherapy and is alive
      with no evidence of recurrence for 2 years.

PMID- 15859648
TI  - Mediastinal mass in a 27-year-old man. Extrapulmonary Coccidioides immitis.

PMID- 15859647
TI  - A 27-year-old man with hyperpigmented patches at upper back and limbs. Primary
      localized cutaneous amyloidosis.

PMID- 15859649
TI  - A right ovarian mass in a 71-year-old woman with ascites and elevated CA 125
      level. Fibrothecoma of the right ovary.

PMID- 15859650
TI  - A retroperitoneal mass in an elderly woman. Pleomorphic rhabdomyosarcoma, classic
      variant, with reactive osteoclast-like giant cells.

PMID- 15859651
TI  - Auer rod-like inclusions in immunoglobulin a multiple myeloma.

PMID- 15859652
TI  - Lipoma of the tuber cinereum.

PMID- 15859653
TI  - Chronic myelogenous leukemia in accelerated phase.

PMID- 15859654
TI  - Clear cell hidradenoma: a mimic of metastatic clear cell tumors.
AB  - Clear cell hidradenoma is a benign skin appendage tumor that may mimic
      conventional-type renal cell carcinoma. Histologically, clear cell hidradenoma
      contains small ductular lumens, focal apocrine and squamoid change, and a less
      prominent vascular pattern than renal cell carcinoma. Furthermore,
      immunohistochemical studies can aid in distinguishing the 2 tumors. Knowing the
      cytologic features of primary skin adnexal neoplasms helps distinguish them from
      cutaneous metastases, which are more commonly referred for fine-needle aspiration
      biopsy evaluation. Detailed clinical history, physical findings, and ancillary
      studies are essential for correct diagnosis and categorization of these tumors.
      We report the rare case of a patient with renal cell carcinoma who underwent
      excision of an axillary clear cell hidradenoma, which was clinically suggestive
      of cutaneous metastatic disease.

PMID- 15859655
TI  - Ectopic decidua of pelvic lymph nodes: a potential diagnostic pitfall.
AB  - Ectopic decidua is one of several benign lymph node inclusions that have been
      increasingly documented in the literature, most often in postmortem examinations
      of pregnant woman and recently in pregnant women with cervical squamous cell
      carcinoma. Although lacking clinical significance of its own, the major
      diagnostic implication would be misdiagnosis as metastatic carcinoma in the lymph
      node. Intraoperative frozen sections are often performed prior to radical
      hysterectomy, leading to a potential alteration of therapy if metastatic
      carcinoma is identified in the lymph nodes. We report such a case of a pregnant
      woman with cervical squamous cell carcinoma requiring lymphadenectomy and
      hysterectomy, in which the intraoperative frozen section of a pelvic lymph node
      with ectopic decidual change was mistakenly identified as metastatic carcinoma.
      Its histologic resemblance to carcinoma and location within subcapsular sinuses,
      compounded with the fact that ectopic lymph node decidua is not commonly seen in
      routine practice, can lead to this diagnostic pitfall. We review the literature
      regarding ectopic decidua, its presence in lymph nodes, and its pathogenesis, as
      well as review the literature on benign lymph node inclusions.

PMID- 15859656
TI  - The unique simultaneous occurrence of granular cell tumor, gastrointestinal
      stromal tumor, and gastric adenocarcinoma.
AB  - Granular cell tumors are generally benign oncocytoid lesions of schwannian origin
      that are often incidental findings in many locations. Gastrointestinal stromal
      tumors occur in older adults and express the c-Kit protein (CD117). Both of these
      tumors have been described in association with many other entities; however, they
      have never been reported to occur jointly. This report is prompted by the
      simultaneous appearance of 2 granular cell tumors, a gastrointestinal stromal
      tumor, and a gastric adenocarcinoma in a 65-year-old woman with a history of
      breast carcinoma and granular cell tumor. To our knowledge, this is the first
      case report of these tumors occurring simultaneously.

PMID- 15859657
TI  - Ichthyosis uteri: a case report and review of the literature.
AB  - Squamous metaplasia of endometrium is mostly manifested by morules or nodules of
      benign nonkeratinizing squamous cells intimately mixed with benign or malignant
      endometrial glands. It has been described with low-grade adenocarcinoma of the
      endometrium, as well as with various benign conditions, including hyperplasia,
      chronic endometritis, and endometrial polyps. However, extensive plaquelike,
      keratinizing squamous change is distinctly uncommon. To our knowledge, we
      describe the first case of extensive benign squamous keratinization with
      underlying endometrial adenocarcinoma.

PMID- 15859658
TI  - A 64-year-old woman with vulvar papule. Vulvar syringocystadenoma papilliferum.

PMID- 15859659
TI  - A 96-year-old woman with a tumorous lesion of the right breast. Invasive
      papillary breast carcinoma of solid variant.

PMID- 15859660
TI  - A 70-year-old man with multiple intra-abdominal masses and liver and spleen
      metastases. Intra-abdominal follicular dendritic cell sarcoma with liver and
      spleen metastases.

PMID- 15859661
TI  - A 53-year-old man with an anterior knee fungating mass. Cutaneous blastomycosis.

PMID- 15859662
TI  - Right upper quadrant pain and fever in a 41-year-old man. Epithelioid
      hemangioendothelioma of the liver with metastasis to porta hepatis lymph nodes
      and lung.

PMID- 15859664
TI  - Doctors, nurses, and storytelling.

PMID- 15859663
TI  - Bilateral pulmonary nodules in a 37-year-old woman with malignant melanoma.
      Pulmonary Langerhans cell histiocytosis (eosinophilic granuloma).

PMID- 15859666
TI  - Locking the stable door after the horse left.

PMID- 15859665
TI  - A new clinical practice guideline on initiation and withdrawal of dialysis that
      makes explicit the role of palliative medicine.
AB  - More than 50,000 long-term dialysis patients die per year, with roughly 20% of
      these deaths after a decision to stop dialysis. After dialysis discontinuation,
      the average dialysis patient lives for only 8 to 12 days. The renal community
      recognizes and recommends a role for palliative care in the end-of-life treatment
      of these patients. This article describes the new clinical practice guideline
      developed by the renal community, Shared Decision-Making in the Appropriate
      Initiation of and Withdrawal from Dialysis, that makes explicit the role of
      palliative medicine in the treatment of dialysis-dependent patients who stop this
      treatment with the expectation that death will follow shortly.

PMID- 15859667
TI  - Lessons from the AIDS epidemic: knowing our patients, knowing ourselves.

PMID- 15859668
TI  - Palliative care in advanced dementia: a randomized controlled trial and
      descriptive analysis.
AB  - BACKGROUND: Few patients with end-stage dementia are enrolled in hospice care. A
      palliative care approach would nonetheless seem to be appropriate in various care
      settings, including the acute care hospital. METHODS: We conducted a randomized
      controlled trial of palliative care in patients with advanced dementia
      (Functional Assessment Staging Tool [FAST] stage 6d-7f) who were hospitalized
      with acute illness. Intervention patients received recommendations by a
      palliative care team with the goal of enhancing patient comfort; control patients
      received usual care without these recommendations. RESULTS: Among 99 patients
      enrolled over 3 years, groups were comparable at baseline in terms of gender,
      age, race, dementia stage, and advance directive status. Outcomes were similar in
      terms of mean number of hospitalizations, average length of stay, and mortality.
      Intervention patients were more likely than control patients to receive a
      palliative care plan (23% versus 4%; p = 0.008), usually on discharge, and more
      decisions were made to forgo certain medical treatments but the numbers were
      small. Fewer patients in the intervention group received intravenous therapy
      throughout the admission (66% vs. 81%, p = 0.025). Overall, additional
      interventions included daily phlebotomy for at least half of the admission (41%),
      systemic antibiotics (75%), and new feeding tubes (44%). Including tubes present
      at the time of randomization, a total of 69% received long-term enteral feeding.
      CONCLUSION: It was difficult for a palliative care research team to influence the
      care of advanced dementia patients in the acute hospital setting. When patients
      have advanced dementia, there may be unique barriers, including perceived
      prognostic uncertainty, difficulty assessing comfort level, and perceptions about
      tube feeding. There must be a reexamination of treatment approaches for this
      severely impaired group of patients. Further study should attempt to identify
      patients prior to the need for acute hospitalization so goals can be established
      when there is less urgency to make life and death decisions.

PMID- 15859669
TI  - Physicians reflect on their lived experiences in long-term AIDS care.
AB  - Throughout the history of the acquired immunodeficiency syndrome (AIDS) epidemic,
      the theoretical and empirical literature has emphasized the stressors related to
      the care of patients with AIDS, and the reluctance of health professionals,
      including physicians, to provide care to patients with AIDS. However, from the
      beginning, there have been individuals who have dedicated themselves to the care
      of patients with AIDS. This descriptive, qualitative study explores the
      perceptions and experiences of five physicians, specializing in AIDS care, within
      a large medical center in New York City. Using principles of qualitative data
      analyses set forth by Carini, the data reveal important themes related to how
      they became involved in AIDS care; the stresses associated with AIDS caregiving
      and ways of coping; the rewards of AIDS care; aspects of the physician-AIDS
      patient relationship and patient characteristics that promote their willingness
      to care; and recommendations to fellow physicians in caring for patients with
      AIDS. From what they have said, and not said, palliative care clinicians,
      educators, and administrators can learn ways of promoting physicians' caregiving
      potential, and understand the value and intimacy of the physician-patient
      relationship, particularly within the context of life-threatening illness. This
      has further implications in promoting the quality of care offered to patients
      with AIDS and to all patients with an incurable illness, as well as insuring
      "safe passage" for patients and for the physicians committed to their care.

PMID- 15859670
TI  - Place of care in advanced cancer: a qualitative systematic literature review of
      patient preferences.
AB  - BACKGROUND: It is commonly written that more patients wish to die at home than
      currently achieve this. However, the evidence for preferences for place of
      terminal care and death has not been systematically reviewed. AIM: To carry out a
      systematic literature review of the preferences for place of care and death among
      advanced cancer patients. METHOD: Studies were identified using systematic
      database searches of MEDLINE (1966-1999), PsychLit (1974-1999), and Bath
      Information Data Service (BIDS) (1981-1999). Studies were assessed and data
      extracted and synthesises following the NHS Centre for Reviews and Dissemination
      guidelines, grading studies according to design and rigor of methods. Studies of
      preferences in the general population and of groups including cancer patients
      and/or their caregivers were included. RESULTS: Eighteen studies determining
      preferences in either the general population or groups including cancer patients
      were identified. Views were obtained prospectively and retrospectively from
      patients, the general population, families, and professionals. Respondents
      indicated preferences for home death (range 49%-100%), except one study of
      patients in the care of a continuing care team in London where only 25%-29% of
      patients wanted a home death, and inpatient hospice was the most favored option.
      However, the response rate of this study was not known. Among the general public
      there was a higher preference for inpatient hospice care among in people with
      recent experience of a close friend or relative's death or dying. Where the views
      of patients, families, and professionals were compared, all respondents broadly
      agreed although patients expressed the strongest home preferences. Only 2 of the
      studies provided longitudinal data, and 9 of the 18 had major deficits in design
      or reporting, such as poor or unknown response rate, unclear or unsystematic
      methods of eliciting preferences or other sample or measurement bias. However,
      sensitivity analysis of only the more robust and larger studies did not alter the
      finding of a preference for home care at the end of life in over 50% of patients.
      CONCLUSIONS: Home care is the most common preference, with inpatient hospice care
      as second preference in advanced illness. Meeting these preferences could be
      important outcomes for services. Study designs in this area need to be improved.

PMID- 15859671
TI  - Performance status assessment in home hospice patients using a modified form of
      the Karnofsky Performance Status Scale.
AB  - The Karnofsky Performance Status (KPS) scale is considered to be the gold
      standard for quantifying the physical functioning of patients with cancer.
      However, problems have been identified with the scoring system when the scale is
      used in the home hospice setting. The goal of this study was to compare
      assessments of performance status using two instruments, the KPS and a modified
      version, the Thorne-KPS (TKPS). The TKPS avoids reference to location of care and
      has new descriptors for assessing the frequency of professional visits and the
      proportion of time spent in bed. Comparisons were made on a sample of 78 home
      hospice patients in Perth, Western Australia. The median score for both scales
      was 60. The scales agreed in 56% of ratings overall but after correcting for
      chance, agreement was reduced to 47%. However, 91% of the 34 discrepancies
      occurred within one or two levels of the 11-point scale. TKPS scores were
      consistently lower than KPS scores and were spread over a wider range of the
      scale. The strongest agreement occurred at the higher levels of performance and
      the weakest agreement was within the middle levels of the scales. Further studies
      are required to determine which of the two scales more accurately reflects
      performance status and survival time. However, the results to date suggest that
      the TKPS may be a more objective and sensitive measure of functional performance
      in home hospice patients.

PMID- 15859672
TI  - Terminal sedation: ethical implications in different situations.
AB  - Terminal sedation (TS) is a recently coined term that may apply to a variety of
      practices with differing ethical implications. Two hypothetical cases are
      presented and contrasted. The first presents the more common scenario in which
      sedation is used for severe distress in a patient very close to death, who has
      stopped eating and drinking. The second case is more problematic: a nonterminally
      ill spinal cord injury patient requests sedation because of psychic distress.
      Sedation is supported in the former, but not the latter case. Suggested
      principles guiding the ethical use of sedation are: (1) While respect for
      autonomy is important, we are not obliged under all circumstances to provide
      sedation. (2) Physician intent matters. In providing sedation the physician's
      primary intent should be to alleviate suffering. (3) Reasonable inferences of
      intent can be made from physician actions, providing safeguards to ensure proper
      care. Sedatives should be titrated to observable signs of distress. (4) Proximity
      to death is a more useful concept than terminality in weighing benefits and
      burdens of sedation. (5) The nature of physician action should depend upon the
      nature of the suffering. Not all suffering is appropriately treated with
      sedation. (6) In patients close to death who have already stopped eating and
      drinking, sedation cannot be said to hasten death through dehydration or
      starvation. (7) Where TS is otherwise appropriate and where dehydration may in
      fact hasten death, ethical concerns may be addressed through informed consent. If
      hydration is refused, TS cannot be considered synonymous with euthanasia.

PMID- 15859673
TI  - Thirty years to the day.

PMID- 15859674
TI  - Between a rock and a sad place.

PMID- 15859675
TI  - Fast facts and concepts: an educational tool.

PMID- 15859676
TI  - The second primary.

PMID- 15859682
TI  - On teaching and learning communication.

PMID- 15859684
TI  - Integrating palliative and curative approaches in the care of children with life
      threatening illnesses.

PMID- 15859686
TI  - Pain management and the bogeyman.

PMID- 15859685
TI  - Japanese patients' preferences for receiving cancer test results while in the
      United States: introducing an advance directive for cancer disclosure.
AB  - BACKGROUND: While disclosure of cancer is routine in the United States, it is not
      in Japan. The primary goals of this investigation were to describe overseas
      Japanese patients' preferences for participation in decisions about cancer; to
      delineate patients' beliefs about how physicians should make cancer disclosure
      decisions; and to assess patients' attitudes about a advance directive for cancer
      disclosure. METHODS: This ethnography utilized data from participant
      observations, 30 interviews, and lay materials. Using the analytic technique of
      immersion and crystallization the data were organized around major themes and
      subthemes. RESULTS: The mean age of the 30 participants was 38 years and most (n
      = 20) were female. While most patients expressed preferences to be told the
      results of cancer testing, the number who did not want to be told increased with
      more advanced cancer stage. Many participants believed decisions about disclosure
      should be influenced by a patient's personality, age, or gender, although the
      relative importance of these factors was variable. Virtually all believed
      circumstances existed when fully competent patients should not be told the cancer
      diagnosis. Most participants were supportive of using an advance directive for
      cancer disclosure. DISCUSSION: These participants' beliefs about many aspects of
      the management of cancer test results differ from recommended approaches to
      conveying cancer test results and discussing the cancer diagnosis in the United
      States. Most encourage the use of an advance directive for cancer disclosure as
      mechanism for physicians to elicit patients' unique preferences for participation
      in decision making about cancer.

PMID- 15859687
TI  - Standards of practice for end-of-life care in correctional settings.

PMID- 15859689
TI  - Formal review of end-of-life care content in pharmacotherapy texts.

PMID- 15859688
TI  - Palliative medicine fellowship programs in the United States: year 2000 survey.

PMID- 15859690
TI  - Perspectives on increased family reports of pain in dying hospitalized patients.

PMID- 15859691
TI  - Quality end-of-life care: where do we go from here?

PMID- 15859692
TI  - Access to hospice care.

PMID- 15859693
TI  - Physicians' and nurses' perspectives on increased family reports of pain in dying
      hospitalized patients.
AB  - Many indicators suggest that care of the dying in Oregon has been improving over
      the past decade. However, results from a recent study suggest that one aspect of
      care of the dying, pain management, may be worsening. In late 1997, family
      reports of moderate and severe pain in dying hospitalized patients increased from
      33% to 57%. This occurred during a volatile time in the Oregon political climate
      associated with events surrounding a second vote on physician-assisted suicide.
      In order to better understand the observed increase better, a statewide sample of
      physicians and nurses was surveyed to obtain their opinions about factors that
      may have contributed to the increased family reports of moderate and severe pain
      in dying hospitalized patients. Seventy-nine percent of respondents endorsed two
      or more factors as partial explanations. These factors include an increase in
      family expectations about pain management (endorsed by 96%), decreased physician
      prescribing (endorsed by 66%), and reduced nurse administration of pain
      medication (endorsed by 59%). Physicians who thought reduced physician
      prescribing was a partial factor rated fears of the Board of Medical Examiners
      and the Drug Enforcement Administration as the most likely explanations for
      decreased prescribing. More research is needed to better understand family
      expectations for end-of-life care, fears of investigation, and pain medication
      practices.

PMID- 15859694
TI  - What terminally ill patients care about: toward a validated construct of
      patients' perspectives.
AB  - BACKGROUND: Citizens have conveyed to professionals that care at the end of life
      is less than optimal. Efforts to improve matters have tended to work in piecemeal
      fashion, on tangible more than personal aspects of care, and without the benefit
      of documented perspectives of those who face dying. Policy initiatives and
      clinical interventions need guidance from a broad framework that is validated by
      patients' perspectives. PURPOSE: Our goals were to: (1) assess the construct
      validity and stability over time of the portions of a conceptual framework that
      concern patients' subjective experiences; (2) develop a foundation for
      measurement of these personally meaningful factors; and (3) examine these
      factors' associations for potential clinical or policy significance. POPULATION:
      Patients were from six diverse geographical areas whose physicians judged their
      survival prognosis to be 6 months or less. Physicians who referred the patients
      were randomly selected from state and specialty association lists. METHODS: We
      used in-person survey methodology and multivariate analysis of patient responses.
      The analysis fell into two parts. Using exploratory factor analysis, we looked
      for evidence of discrete dimensions of experiences. Using regression analysis, we
      examined associations among them. RESULTS: Of 1,131 eligible patients, 988 were
      interviewed (87.4% response rate). Of 682 patients who survived to follow-up
      interview 4-6 months later, 650 were interviewed (95.3% response rate).
      Exploratory factor analysis identified 12 discrete factors (accounting for 55% of
      variance; maximum Spearman's p = 0.24), 8 of which met criteria for representing
      measurable dimensions (accounting for 46% of variance). These 8 were: patient
      clinician relationship; social connectedness; caregiving needs; psychological
      distress; spirituality/religiousness; personal acceptance; sense of purpose; and
      clinician communication. Eigenvalues ranged from 1.45 to 6.30 and Cronbach's
      alpha from 0.63 to 0.85. The concordance between these dimensions and those in
      the proposed framework indicated that two dimensions required minor modifications
      and six were confirmed, providing evidence of good construct validity for this
      portion of the framework. The same dimensions were also evident at follow-up
      except that the first two above-listed loaded on one combined factor, clinician
      interaction (eigenvalues 1.83-7.92; Cronbach's alpha from 0.64 to 0.86). This
      provides evidence of the construct's stability over time. Clinical communication
      and patient-clinician relationship were associated (odds ratio [OR] 2.79, 2.31
      3.36). Better clinician communication correlated with somewhat better personal
      acceptance (OR 1.10,1.02-1.19), and a better patient-clinician relationship
      correlated with less psychological distress (OR 0.84, 0.75-0.95). CONCLUSIONS: We
      conclude that: (1) Personally meaningful aspects of patients' experience of
      terminal illness can be represented in valid, multidimensional constructs that
      are stable over time; (2) They are measurable; and (3) Aspects of the therapeutic
      relationship appear to correlate with patients' experience of the dying process.

PMID- 15859695
TI  - Access to hospice: a perspective from the bereaved.
AB  - Access to hospice care continues to be an enigma. Hospice has been available for
      nearly three decades in the United States, but the services continue to be
      underutilized. In an effort to better understand access barriers, a series of
      focus groups were held with recently bereaved caregivers (mean = 9.9 months since
      the death of the patient). During the process of the focus group discussions,
      participants relived their experience with hospice. Although the purpose of this
      research was to ascertain access recommendations, participants integrated their
      access comments into the overall richness of their hospice experience. The 12
      participants were divided into two groups, and each group met twice with a 2-week
      interval between sessions. From the focus group discussions, six themes emerged.
      Two of the six themes related to access issues: (1) societal and health system
      issues related to delayed hospice access and (2) education and practice needs of
      health professionals that affect hospice access. Participants provided
      recommendations to address the concerns expressed through both of these access
      themes.

PMID- 15859696
TI  - Physician board certification in hospice and palliative medicine.
AB  - The American Board of Hospice and Palliative Medicine (ABHPM) was formed in 1995
      to establish and implement standards for certification of physicians practicing
      hospice and palliative medicine and, ultimately, accreditation of physician
      training in this discipline. The ABHPM has created a certification process that
      parallels other member boards of the American Board of Medical Specialties
      (ABMS). After 3(1/2) years and the administration of seven examinations, 623
      physicians have achieved board certification in hospice and palliative medicine.
      Those with ABMS primary board certifications have been certified by
      anesthesiology, 4%; family practice, 23%; internal medicine, 55%; pediatrics, 1%;
      radiation oncology, 2%; and surgery, 2%. The majority describe their practice
      location as urban. Sixty-nine percent report more than 5 years of clinical
      experience in hospice/palliative medicine and 75% report an association with a
      hospice as medical director or hospice physician. Sixty-seven percent belong to
      the American Academy of Hospice and Palliative Medicine. Applicants were drawn
      from 48 states, Canada, and 3 foreign countries. The available data indicate only
      20% were less than 40 years of age and that two-thirds were men. There is
      significant physician interest in seeking professional recognition of expertise
      in caring for terminally ill persons and their families through creation of a
      specialty in hospice and palliative medicine. Certification of physicians and
      accreditation of training programs are key elements in this process. This process
      will encourage more physicians to enter this field and provide needed expertise
      in the management of patients with progressive disease for whom the prognosis is
      limited, and the focus of care is quality of life.

PMID- 15859697
TI  - The bedside confusion scale: development of a portable bedside test for confusion
      and its application to the palliative medicine population.
AB  - BACKGROUND: Clinical tests for confusion in medically ill patients are frequently
      burdensome and difficult to use. Available tests lack portability and tend to be
      shunned in clinical practice by physicians. OBJECTIVE: To develop a simple,
      sensitive bedside test for confusion. DESIGN: Prospective comparison study.
      SETTING: An in-patient palliative medicine unit in a large urban hospital.
      PATIENTS: Thirty-one consecutive patients admitted to the unit. INTERVENTION:
      None. MEASUREMENTS: A 2-minute screening test, the Bedside Confusion Scale (BCS),
      which utilizes an observation of level of consciousness at the time of clinical
      interaction, followed by a timed task of attention, was administered to 31
      consecutively admitted patients. The results were compared to a previously
      validated test, the Confusion Assessment Method (CAM). The BCS and the CAM were
      scored in standardized fashion and results of the two populations compared.
      Demographic and clinical characteristics of the patient population, along with
      the Karnofsky performance scores (KPS) and neurological findings were registered.
      RESULTS: Using the CAM as the reference standard, the sensitivity of the BCS was
      100%. Worsening KPS and more abnormalities on neurological examination were seen
      across normal (BCS = 0), borderline (BCS = 1), and abnormal (BCS >/= 2) groups (p
      > 0.01, trend test). CONCLUSIONS: In an in-patient palliative medicine
      population, the BCS correlates with the previously validated CAM and exhibits
      high sensitivity, an essential quality of a useful screening test.

PMID- 15859698
TI  - Adult education program in palliative care for nursing facility physicians:
      design and pilot test.
AB  - Nursing facilities (NF) are important sites for the care of dying patients.
      Curricula likely to improve end-of-life care are needed for NF physicians. To
      this end, a model medical school palliative care curriculum was modified for
      experienced NF physicians. Adult learning techniques were emphasized, as well as
      interactions likely to change physician behavior. Inclusion of the opinion
      leader, audit with feedback, use of consensus guidelines, and other techniques
      for changing physician behavior were included. Written materials to supplement
      the course were identified. This new program was pilot tested and improved. An
      initial audit of physician practices and survey of the NF staff, a half-day adult
      educational session, and follow-up with the NF medical director is suggested.
      This intervention should be tested to determine if it improves patient end-of
      life care outcomes in this setting.

PMID- 15859699
TI  - Management of seizures in brain tumor patients at the end of life.
AB  - Few data exist on the management of seizures in brain tumor patients near the end
      of life. This article provides information on the epidemiology and phenomenology
      of seizures, as well as on differential diagnostic considerations. Based largely
      on empirical data from the pediatric epilepsy literature, guidelines for
      management of seizures near the end of life are given, with emphasis on the use
      of rectal antiepileptic drugs.

PMID- 15859700
TI  - See one, do one, teach one: thoughts on medical training and end-of-life care.

PMID- 15859701
TI  - In the cracks.

PMID- 15859703
TI  - To cure, sometimes. To comfort, always.

PMID- 15859704
TI  - Planning for the evaluation of a pediatric end-of-life curriculum.
AB  - BACKGROUND: Decision making at the end of life can be complex and emotionally
      challenging for healthcare providers, particularly in pediatrics. Unfortunately,
      few undergraduate and graduate medical education curricula adequately address
      these issues. In this article, we describe the plan and progress to date of the
      design, implementation, and evaluation of an end-of- life curriculum for
      pediatric residents. NEEDS ASSESSMENT: Prior to the development of a formal end
      of-life curriculum, a survey was given to a single cohort of residents four times
      over the course of their training to assess their attitudes toward end-of-life
      issues and their experience with the informal curriculum in residency. Entering
      pediatric residents felt relatively uncomfortable dealing with death and dying,
      but by the end of training, residents felt more comfortable dealing with these
      issues. Residents were relatively ambivalent about the degree to which their
      education helped them to deal with end-of-life issues. CURRICULUM DEVELOPMENT AND
      EVALUATION PLAN: A number of curricular interventions were developed including a
      noon conference series, grand rounds presentations, a 3-hour seminar on giving
      bad news, and written information for the housestaff manual. The curriculum was
      implemented in the fall of 1999. The impact of the curriculum will be assessed
      using a single interventional group with historical control study design. The
      evaluation instruments will include the previously used survey and an objective
      written examination. The 3-hour seminar will be assessed with a pre-test post
      test crossover design using standardized patients. DISCUSSION: This rigorous,
      feasible, and cost-effective approach to curriculum development is intended to
      serve as a model for end-of-life education in pediatric residencies.

PMID- 15859705
TI  - Can depression be a terminal illness?

PMID- 15859710
TI  - Dying inside the walls.

PMID- 15859711
TI  - Hospice in prison: the Louisiana State Penitentiary Hospice Program.
AB  - This article by the hospice case manager and inmate volunteer coordinator at the
      Louisiana State Penitentiary (LSP) hospice program describes the program's major
      features, how it was started and is sustained within the confines and culture of
      prison life, and how the challenges to implementing a hospice program within a
      maximum security prison continue to be met. Recommendations are offered for
      undertaking a hospice initiative in a correctional facility. The LSP Hospice
      Program was honored in May 2000 with the Circle of Life Award from the American
      Hospital Association. This article is excerpted from a thematic issue, "Hospice
      in Prison," Volume 2, Number 3, 2000 of the online journal, Innovations in End-of
      Life Care at http://www.edc.org/lastacts/

PMID- 15859713
TI  - A security officer's view of the Louisiana State Penitentiary Hospice Program.

PMID- 15859712
TI  - Room number six.

PMID- 15859714
TI  - Feeding tubes at end-of-life: the lack of physician leadership.

PMID- 15859716
TI  - Goals and strategies for teaching death and dying in medical schools.
AB  - Teaching medical students to respond to needs of the dying represents an
      important challenge for medical educators. This article describes the goals and
      objectives that should be identified before medical schools can meet this
      challenge, as well as strategies that, when implemented, will provide students
      with the necessary knowledge, skills, and attitudes to meet the needs of the
      dying patients. The goals and objectives were identified through a modified group
      consensus process developed during Choice In Dying's 5-year project "Integrating
      Education on Care of the Dying into Medical Schools." The authors have diverse
      experiences and backgrounds and are actively involved in death and dying teaching
      at 11 medical schools. They conclude that after accepting the goals and
      objectives, key medical school faculty can work cooperatively to develop
      strategies to integrate them into the school's curriculum. Without first
      establishing a set of goals and objectives and developing evaluation methods,
      medical schools could miss their mark in fostering the student's ability to care
      for the dying.

PMID- 15859717
TI  - Ambivalence and ambiguity in hospitalized, critically ill patients and its
      relevance for palliative care.

PMID- 15859718
TI  - Cancer patients say the darnedest things: commentary on "paradoxes in cancer
      patients' advance care planning".

PMID- 15859719
TI  - Paradoxes in cancer patients' advance care planning.
AB  - PURPOSE: To determine the frequency of advance care planning (ACP) in
      hospitalized cancer patients and to assess their reactions to a proposed policy
      in which medical housestaff would offer to discuss ACP at the time of hospital
      admission. METHODS: Structured interviews with 111 consecutively admitted cancer
      patients on the oncology inpatient service of a tertiary care medical center.
      RESULTS: We found that 69% (77/111) of patients had discussed their advance care
      preferences with someone, usually a family member, and 33% (37/111) had completed
      at least one formal advance directive (e.g., a living will or durable power of
      attorney for health care); 32% (36/111) had done both; and 30% (33/111) had done
      neither. However, only 9% (10/111) of patients reported having discussed their
      advance care preferences with their clinic oncologists and only 23% (23/101) of
      the remaining patients stated that they wished to do so. By contrast, 58%
      (64/110) of patients supported a policy in which medical housestaff would offer
      to discuss these advance care preferences as a part of the admission history.
      CONCLUSIONS: Our data suggest that while oncology inpatients frequently have ACPs
      that they discuss with family and/or document in formal advance directives, they
      rarely discuss or wish to discuss these ACPs with clinic oncologists. We also
      show that most of the reticent patients would nevertheless consider discussing
      the same ACPs with admitting housestaff on the day of hospital admission.

PMID- 15859720
TI  - Preferences for life-sustaining treatments in advance care planning and surrogate
      decision making.
AB  - BACKGROUND: Surrogates and clinicians often make treatment decisions for
      decisionally incapacitated patients with limited knowledge of their preferences.
      This study examined patients' life-sustaining treatment preferences to facilitate
      advance care planning discussions and surrogate decision making. METHODS: We
      interviewed 342 participants from 7 groups: younger and older well adults;
      persons with chronic illness, terminal cancer, and acquired immunodeficiency
      syndrome (AIDS); stroke survivors; and nursing home residents. Preferences for
      antibiotics, short- and long-term mechanical ventilation, hemodialysis, tube
      feeding, and cardiopulmonary resuscitation (CPR) were elicited for each
      participant's current health state and three hypothetical health states
      representing severe dementia, coma, and severe stroke. RESULTS: Participants
      chose to forego more invasive or long-term treatments at a higher rate than less
      invasive, short-term treatments in all health states. Participants were much more
      willing to forego treatments in coma than in their current health state, with
      stroke and dementia somewhere in between. Participants who were older, female,
      had worse functional status, had more depressive symptoms, or lived in a nursing
      home were more inclined to forego treatment in their current health state. In
      contrast, treatment preferences in hypothetical health states showed either no
      associations or much weaker associations with these factors. Participants who
      were willing to accept more invasive treatments were highly likely to accept less
      invasive treatments and participants who preferred to forego a less invasive
      treatment were highly likely to forego more invasive treatments. Participants who
      preferred to receive a treatment in a health state with severe impairments were
      highly likely to want the same treatment in a less impaired health state.
      Similarly, participants who preferred to forego a treatment in a less impaired
      health state were highly likely to forego the same treatment in a more impaired
      state. CONCLUSIONS: In advance care planning discussions, clinicians might
      explore with patients their preferences about short- and long-term treatments
      with variability in their invasiveness (including CPR) in both their current
      health state and hypothetical situations representing different levels of
      functional impairment. When surrogates have no knowledge about the wishes of
      formerly competent patients, clinicians may help them with medical decisions by
      discussing what other people commonly want in similar circumstances.

PMID- 15859721
TI  - Opioid type and other clinical predictors of laxative dose in advanced cancer
      patients: a retrospective study.
AB  - BACKGROUND: Constipation is a frequent and underdiagnosed complication in
      patients with advanced cancer. Constipation in this population is multifactorial,
      but the use of opioids is one of the main causes. The purpose of this
      retrospective study was to establish the association between opioid type and
      laxative dose, as well as the contribution of other clinical factors in advanced
      cancer patients admitted to a palliative care unit. METHODS: The records of
      consecutive patients admitted to the Acute Palliative Care Unit at the Grey Nuns
      Hospital between December 1995 and January 1997 were reviewed. Criteria of
      eligibility were the presence of cancer pain treated by opioids (oral and
      subcutaneous morphine and hydromorphone, oral methadone), oral laxative treatment
      capable of achieving at least one bowel movement every 3 days, and the absence of
      bowel obstruction or colostomy. During period(s) of stable analgesic doses, the
      charts were reviewed for demographic and clinical characteristics, average number
      of bowel movements, daily laxative doses, doses and type of opioid,
      laxative/opioid dose ratio (LOR) (calculated by dividing the total laxative dose
      by the total opioid dose), functional and cognitive status, food intake, and
      level of calcium, albumin, and potassium. RESULTS: Forty-nine evaluable patients
      were identified. The LOR in patients receiving oral opioids was 0.15 +/- 0.19 vs.
      0.18 +/- 0.17 in patients on parenteral opioids (p > 0.2). The LOR in patients
      receiving methadone was 0.025 +/- 0.027 as compared to 0.24 +/- 0.23 in patients
      receiving morphine and 0.17 +/- 0.13 in patients on hydromorphone (p < 0.0001).
      We found a strong association between LOR and abdominal involvement (p < 0.0006),
      opioid type (p < 0.0001), age (p < 0.0001), and female gender (p < 0.034). There
      were no significant correlation between LOR and functional status, cognitive
      status, food intake, and level of calcium or potassium. CONCLUSION: We conclude
      that laxative dose needs to be titrated on an individualized basis. The LOR is
      lower in patients receiving methadone and in those of male gender, younger age,
      and absence of abdominal involvement.

PMID- 15859722
TI  - Palliative care/hospice and the withdrawal of dialysis.
AB  - While the majority of end-stage renal disease (ESRD) patients on dialysis lead
      satisfying lives, an increasing number are choosing to withdraw from dialysis
      before death. A partnership between nephrology and palliative care/hospice
      healthcare teams would seem likely in the care of ESRD patients, yet this is
      often not the case. In anticipation of increasing participation by palliative
      care/hospice teams in the care of such patients, this article reviews the
      decision-making process of withdrawal and the medical care of the patient who
      withdraws. While withdrawal can be an acceptable choice from a medical, legal,
      psychiatric, and ethical point of view, it can nonetheless be complex. Profound
      decisions are often characterized by the need for time to process, and by
      ambivalence among patient, family and healthcare providers. In addition to caring
      for the patient and family, the palliative care/hospice team will want to
      consider the needs of the referring nephrology team as well. A "uremic death" is
      characterized as painless; however, other symptoms related to the accumulation of
      toxins and fluid can be anticipated and managed. Pharmacological intervention of
      uremic symptoms, as well as the pain attendant to other, nonrenal comorbid
      disease is accomplished with awareness of the impact of renal failure on the
      excretion of various drugs and their metabolites.

PMID- 15859723
TI  - Communication in caring for terminally ill patients.
AB  - Good care for dying patients has always been an obligation in medicine. To
      fulfill this obligation, physicians must embrace the integralness of dying in
      life, must recognize when to submit to death and dying with equanimity, and must
      develop attentive and individualized plans of care for each patient. Approaches
      to care should have, at their core, a reinvigorated commitment to communication
      between health professionals and patients and their intimates.

PMID- 15859724
TI  - Special techniques in palliative radiation oncology.

PMID- 15859725
TI  - It's not the dying.

PMID- 15859726
TI  - Introduction to the National Consensus Conference on Medical Education for Care
      Near the End of Life: executive summary.

PMID- 15859727
TI  - Case discussions in palliative medicine.

PMID- 15859733
TI  - Oncology and palliative care: are oncologists evil, or just oblivious?

PMID- 15859734
TI  - Innovations in end-of-life care: improving quality by focusing on the process of
      change.

PMID- 15859736
TI  - Palliative care in Spain: an evolving model.

PMID- 15859735
TI  - Designing and sustaining a palliative care and home hospice program.

PMID- 15859737
TI  - Taking a spiritual history allows clinicians to understand patients more fully.

PMID- 15859739
TI  - Talking about dying: a clash of cultures.

PMID- 15859740
TI  - New End-of-Life Guidelines.

PMID- 15859741
TI  - The future of the palliative medicine fellowship.
AB  - The field of palliative medicine has grown rapidly in recent years, and its
      growth has been accompanied by increasing interest in palliative care education.
      This editorial suggests that the field's growth to date has been aided by
      palliative medicine training programs that are based on an "apprentice" model.
      However, if the field of palliative medicine is to enjoy continued growth in the
      future, this model will be insufficient. Instead, it will be essential that
      palliative care training programs shift to a more traditional "academic" model of
      postgraduate education.

PMID- 15859742
TI  - Coding and reimbursement mechanisms for physician services in hospice and
      palliative care.
AB  - Many physicians misperceive that the current coding system used to bill third
      party payers in the United States does not include codes related to hospice and
      palliative care. This article will help physicians and hospice and palliative
      care providers to: 1) understand how to code for physician services related to
      hospice and palliative care; 2) review the documentation required to support such
      services; 3) understand the differences between the reimbursement mechanisms to
      be used when the patient is enrolled in the Medicare Hospice Benefit, and the
      usual reimbursement mechanisms; and 4) understand some of the approaches for
      funding non-physician palliative care services for patients not enrolled in the
      Medicare Hospice Benefit.

PMID- 15859743
TI  - Potential medicare reimbursements for services to patients with chronic fatal
      illnesses.
AB  - Medicare's payment and coverage patterns most readily serve beneficiaries' needs
      for episodic interventions such as surgery and diagnostic tests. Except in
      hospice, supportive services for long-term, worsening illnesses have not been
      central to financial policies. Thus, providers who aim for comprehensive, high
      quality programs for patients facing serious and eventually fatal illness must
      work within complex reimbursement structures that do not fit patients' needs
      well. In acute settings, long-term care settings, home health, physicians' visits
      and hospice, the rules for Medicare reimbursements differ and are rapidly
      changing. Consequently, many providers do not know how to bill for appropriate
      care for a person who is very sick and expected to die. Many health-care provider
      organizations want to enhance services to seriously ill patients and their
      families by initiating organized palliative care programs. Often, organization
      leaders are unfamiliar with regulatory and reimbursement issues for palliative
      care, especially as patients cross programs. This article provides an overview of
      the reimbursement approaches for Medicare payments. This information gives a
      foundation for estimating a business plan, for discussions with fiscal
      intermediaries and with other area provider organizations, and for making
      financially viable strategic improvements in care for seriously ill patients.

PMID- 15859744
TI  - The impact of a regional palliative care program on the cost of palliative care
      delivery.
AB  - In July 1995 the Edmonton Regional Palliative Care Program (ERPCP) was
      established in the City of Edmonton to increase the access of patients with
      terminal cancer to palliative care services, decrease the number of cancer deaths
      in acute-care facilities, and increase the participation of family physicians in
      the care of terminally ill patients. The objective of this retrospective study
      was to determine the cost of implementation of the ERPCP and savings in acute
      care facility costs after its implementation. We did this by comparing the cost
      of care for patients during 1992-93 (prior to the ERPCP) and 1996-97 (with the
      ERPCP). The main outcome measures were the cost of care and the total hospital
      stay in days for all patients during their last acute-care hospital admission.
      The increased funding for the ERPCP was offset by a significant decrease in the
      overall cost of palliative care in the acute-care facilities. There was a
      substantial decrease in the palliative care costs in acute facilities from
      11,963,846 dollars in 1992/93 to 3,449,055 dollars in 1996/97. This can be
      explained by the significant decrease in the number of palliative care patient
      days in acute-care facilities from 22,608 during 1992/93 to 6085 during 1996/97.
      Physician billings were slightly higher for 1996 as compared to 1992. In 1992,
      90% (195,117/427,780) of the billings were made by the specialists (internists,
      surgeons, and other specialists), while in 1996/97 67% (359,869/537,342) of the
      payments were made to primary care practitioners (p < 0.0001). Overall, there
      were estimated saving of 1,650,689 dollars for palliative care costs in 1996/97
      as compared to 1992/93. Our results suggest that the establishment of an
      integrated palliative care program reduced the cost of care. Prospective cost
      measurement studies are required.

PMID- 15859745
TI  - Palliative care in cystic fibrosis.
AB  - Although advances in therapy for cystic fibrosis (CF) have dramatically increased
      the average life span of patients, the disease is still uniformly fatal. Little
      attention has been paid to methods of palliative care for patients with cystic
      fibrosis in the medical literature. The primary palliative care issue in end
      stage CF is the management of dyspnea. An observational study done at Children's
      Hospital in Boston suggested that doses of morphine in the range of 5 mg per hour
      can control the end-stage dyspnea in CF of over 50% of patients; the rest
      required increasing doses with the highest dose required being 30 mg/hour. The
      use of mechanical ventilation at the end of life is increasing in CF,
      particularly for those patients awaiting lung transplantation, and it appears
      that the consensus against the use of aggressive care at the end of life in CF
      may be eroding. The use of various modes of assisted ventilation in end-stage CF
      will add new challenges to the compassionate provision of end-of-life care. In
      addition to these medical issues, palliative care in CF presents some unique
      psychosocial issues: there may be more than one family member with the disease,
      and there is an involved patient community also affected by end-of-life plans. A
      family-centered approach to end-of-life care for patients with CF is essential.

PMID- 15859746
TI  - Parenteral lidocaine for severe intractable pain in six hospice patients
      continued at home.
AB  - A small number of patients at the end of life suffer from severe or intractable
      pain that is difficult to manage with opioids. We have observed that lidocaine
      infusions successfully treat otherwise severe refractory pain syndromes. In
      general, the lidocaine infusion is continued for a few days and gradually
      supplanted by oral adjuvant analgesics or by invasive pain management techniques.
      We report six cases where prolonged lidocaine infusions were successfully
      continued in the home care setting. The average lidocaine infusion rate was 44
      mg/hour (range 10-80 mg/h), serum levels ranged from 1.5-9.3 microg/mL, and
      duration of therapy ranged from 24-240 days. Mechanisms of action of lidocaine
      and sodium channel blocking adjuvant analgesics are reviewed. Parenteral
      lidocaine deserves additional study for its ability to relieve pain in terminally
      ill patients.

PMID- 15859747
TI  - An oncologist in the house: home visit vignettes.

PMID- 15859748
TI  - Capturing the richness of palliative education outcomes through the use of focus
      groups.

PMID- 15859749
TI  - Dealing with anger about pain management.

PMID- 15859752
TI  - Communication between professions: doctors are from mars, social workers are from
      venus.

PMID- 15859754
TI  - Institutional accountability in end-of-life care: organizational leadership,
      measurement, and consumer demand.

PMID- 15859755
TI  - Measuring quality of care in palliative care services.

PMID- 15859756
TI  - Using the STAS in a Palliative Care Unit in Cremona, Italy.

PMID- 15859759
TI  - Changing the system.

PMID- 15859761
TI  - Racial disparity in advance care planning.

PMID- 15859760
TI  - Do we need a new specialty? An editorial reply.

PMID- 15859762
TI  - Beyond reliability and validity: analysis of selected quality-of-life instruments
      for use in palliative care.
AB  - The purpose of this study was to review quality-of-life instruments for their
      potential usefulness in the palliative care setting. Conceptualizations of
      quality of life throughout history, and contemporary conceptualizations of
      quality of life were briefly discussed. The specific conceptualizations of six
      quality-of-life measurement tools (the Medical Outcomes Study Short-Form Health
      Survey [SF-36], the European Organization for Research and Treatment of Cancer
      [EORTC] QLQ-C30, the Quality of Life Index [QLI], the Hospice Quality of Life
      Index [HQLI], the McGill Quality of Life Questionnaire [MQOL], and the Missoula
      VITAS Quality of Life Index [MVQOLI]) were evaluated. The origins, target
      populations, acceptability of individual items, completion time, number of
      questions, type of response format, and type of scoring of each instrument were
      discussed, and evidence of the instruments' reliability, validity, and
      responsiveness were reviewed. The researcher or clinician should consider all of
      these factors when choosing the quality-of-life instrument that best fits the
      purpose.

PMID- 15859763
TI  - The effect of age on medical decisions made by patients with chronic illness.
AB  - Patients are currently encouraged to appoint surrogates to make healthcare
      decisions for them in the event that they are not able to make those decisions
      for themselves. Many studies have suggested that in hypothetical situations,
      surrogates often make different decisions than the still-capacitated patients say
      they would make. Age difference between patient and appointed surrogate is one
      possible explanation because many surrogates are next-generation relatives. This
      study evaluated differences in end-of-life decision making between elderly and
      younger patients with chronic disease. Two age groups were interviewed: (1)
      geriatric patients aged 70 and older and; (2) acquired immunodeficiency syndrome
      (AIDS) patients aged 30-50. Subjects who demonstrated an understanding of
      cardiopulmonary resuscitation (CPR) and artificial nutrition and hydration (ANH)
      were asked to choose, on a five-point Likert scale, whether they would want these
      treatments for themselves in four hypothetical scenarios: (1) an older person in
      a coma after a car accident; (2) a younger person in a coma after a car accident;
      (3) an older person with Alzheimer's disease; (4) a younger person with AIDS
      dementia. One hundred seventy-six subjects were included: 84 geriatric patients
      and 92 AIDS patients. Differences in the two groups were significant only in the
      scenario of an older person in a coma after a car accident (p = 0.007), with the
      geriatric patients wanting more treatment. The lack of significant differences
      between healthcare decisions made by the two groups under the hypothetical
      scenarios utilized in this study may indicate that age differences will not
      prevent a next-generation healthcare agent from making substituted judgement that
      accurately reflects patient wishes.

PMID- 15859764
TI  - Case report; effective community palliation of intractable malignant ascites with
      a permanently implanted abdominal drain.
AB  - A patient with intractable malignant ascites from metastatic tabular breast
      carcinoma underwent insertion of a Tenckhoff catheter in July 1997. Seventeen
      months later the patient continues to have excellent symptomatic relief, without
      complications, by self-drainage of ascites at home. Tenckhoff catheter can be
      useful in the management of intractable malignant ascites.

PMID- 15859768
TI  - Teaching signs and symptoms assessment skills: solutions to difficult teaching
      issues in palliative care.

PMID- 15859765
TI  - Feasibility of a healthcare proxy counseling program for patients with
      Alzheimer's disease.
AB  - BACKGROUND: Although significant progress has been made in the implementation of
      advance directive counseling programs for cognitively intact patients, there is a
      paucity of information on the outcome of these programs with patients with
      Alzheimer's disease. This study investigated the prevalence of completed
      healthcare proxies in a sample of Alzheimer's disease outpatients, and the
      feasibility of a systematic proxy counseling program for this population.
      METHODS: The setting was a geriatric psychiatry clinic. Ninety-four patients with
      Alzheimer's disease were surveyed for their previous completion of a healthcare
      proxy. All patients with capacity and without a proxy were approached to complete
      the advance directive with a lay counselor. RESULTS: Thirty-two percent (n = 30)
      of patients had completed a proxy prior to the initiation of a counseling
      program. Of patients without proxies (n = 64), 89% had capacity to complete one.
      Seventy-nine percent subsequently completed a proxy through the counseling
      program. Hispanics were least likely to have had a proxy prior to initiation of
      the program, yet were very willing to complete the document. CONCLUSIONS: The
      majority of patients with Alzheimer's disease in an outpatient setting did not
      have healthcare proxies, yet had the capacity and motivation to complete this
      advance directive. With physician input regarding the presence of decisional
      capacity, a lay counselor successfully implemented the counseling process. These
      results support the initiation of similar counseling programs for Alzheimer's
      outpatients.

PMID- 15859772
TI  - A feeling for the humanities, in a short white coat.

PMID- 15859775
TI  - Initiative for the terminally ill on Medicare.

PMID- 15859776
TI  - Perspectives on palliative care: a chair of medicine viewpoint.
AB  - Palliative care should integrate well into academic medicine. The diversity of
      patients served and the attraction of the sickest of patients mandate palliative
      care as well as disease directed therapy. The themes of coping, caring and
      symptom management are daily needs at a university hospital. A chair of medicine
      with a background as a hospice medical director can provide valuable support to
      physicians as well as to the patients. Research and new models of palliative care
      can be developed, often in conjunction with the community. The provision of
      longitudinal care and symptom management are not incongruous with the mission of
      research. They are inseparable.

PMID- 15859777
TI  - Last acts task forces, resource committees focus on changing care at the end of
      life.

PMID- 15859778
TI  - Learning empathy: medical school and the care of the dying patient.
AB  - Medical education has traditionally been focused on the understanding of
      pathophysiology and treatment of disease. While there is an increasing level of
      attention focused on the doctor- patient relationship and the social aspects of
      medicine, there remains a relative lack of educational efforts regarding the care
      of individuals who are dying. This paper addresses the cultural context of
      medical school with respect to end-of-life care and proposes the role of
      physicians in caring for dying patients. In addition we report initial efforts at
      the University of Vermont College of Medicine to construct a preclinical course
      for medical students about end-of-life issues. As part of these efforts we sought
      to assess the attitudes of entering medical students towards end-of-life care.
      Review of the data suggests that the majority (66-98%, depending on measure used)
      of new medical students possess sophisticated attitudes regarding the care of
      dying individuals. Our conclusion is that medical education should seek to
      nurture these sophisticated attitudes and supply the basic tools of palliative
      care in order to improve the quality of experience for individuals who are dying.

PMID- 15859779
TI  - Using a patient perspective to improve palliative education: helping patients go
      into that good night.

PMID- 15859780
TI  - Quality of life in advanced ovarian cancer: identifying specific concerns.
AB  - PURPOSE: To identify issues affecting the quality of life (QoL) in women
      receiving palliative therapy for ovarian cancer. METHODS: Twenty women with
      advanced recurrent ovarian cancer were interviewed to establish what issues
      affect QoL. All patients were receiving palliative chemotherapy or other
      palliative therapy in the department of Gynecologic Oncology at the Massachusetts
      General Hospital, and were felt to have a life expectancy of 1 year or less by
      best clinical estimate. RESULTS: Twenty patients with an average age of 56.7
      years participated. Psychosocial issues were more common than physical ones, and
      patients were more likely to mention issues that positively impact on QoL rather
      than those with a negative effect. Most patients noted that a sense of hope,
      enhanced appreciation for day to day life, and a strong support system had a
      significantly positive effect on QoL. Issues negatively impacting QoL included
      fear of their disease (90%) and concern for family and friends (100%),
      particularly children. Most common physical symptoms impacting QoL included
      fatigue (100%) and anorexia (55%). CONCLUSIONS: Little research has been done
      into QoL issues for ovarian cancer patients receiving palliative care. Available
      QoL studies tend to focus on the physical aspects of a disease or its treatment.
      This pilot study suggests that women with advanced, recurrent ovarian cancer feel
      that psychosocial issues play a greater role in determining QoL than do physical
      issues. Further QoL studies for these patients should include assessment of
      psychosocial realms. This information can then be used to design interventions to
      improve QoL.

PMID- 15859781
TI  - The use of an electronic patient record system to identify advanced cancer
      patients and antidepressant drug use.
AB  - PURPOSE: Psychiatric morbidity is common in cancer patients toward the end of
      life. In this study, we demonstrate the use of an electronic patient record
      system to identify patients with advanced cancer, and then analyze practice
      patterns regarding the use of antidepressants. PATIENTS AND METHODS: Using
      electronic patient records from January 1986 to December 1996, we identified
      17,476 patients with possible cancer. Patients were identified by virtue of
      having any one of eight markers. We used an iterative process to modify the
      specificity of these markers, and an advanced cancer cohort was assembled
      consisting of 1185 patients. RESULTS: A random sample of 200 written medical
      records were reviewed, of which 157 records (78.5%) were retrieved. Extracted
      information was reviewed by an oncologist, and patients were classified as
      follows: (1) no evidence of cancer; (2) evidence of cancer with an expected
      survival of less than or equal to 24 months; or (3) evidence of cancer with an
      expected survival of more than 24 months. Overall, 86% of the advanced cancer
      sample assembled from electronic records was correctly classified as advanced
      cancer by the review of the written records. Overall, 16% of all 1185 patients
      with advanced cancer were exposed to at least one antidepressant, with 3% of
      patients exposed to a selective serotonin-reuptake inhibitor, 10% exposed to a
      tricyclic antidepressant at a dose of greater than 25 mg, and 4% exposed to a low
      dose of a tricyclic antidepressant. CONCLUSION: The electronic patient record can
      be used to assemble an advanced cancer cohort for the purpose of studying
      palliative care practice patterns. Antidepressants are seldom part of the
      palliative management of this population.

PMID- 15859782
TI  - Humanistic qualities in end-of-life care: lessons from the diving bell and the
      butterfly: a memoir of life in death-required reading in an end-of-life care
      curriculum for internal medicine residents.
AB  - OBJECTIVE: Reading a literary account of a terminal illness to develop humanistic
      qualities and attitudes for effective end-of-life care. METHOD: The Diving Bell
      and the Butterfly: A Memoir of Life in Death by Jean-Dominique Bauby is an
      autobiographical account of Mr. Bauby's experiences in the locked-in state after
      he suffered a brain stem stroke at age 43. Each resident was given a copy of this
      paperback to read over 4 weeks. Interns (PGY-1) were on a 4-week oncology ward
      rotation, and all junior and senior residents (PGY-2 and PGY-3) were on elective
      rotations during this period. Residents were instructed to mark their favorite
      passages of the book, to be prepared to read aloud such passages in small-group
      sessions, and to explain why they chose the specific passage. Attendance was
      mandatory, and residents were asked to complete a questionnaire at the end of the
      small-group discussion. RESULTS: Eighteen PGY-ls and 30 PGY-2/3s completed the
      curriculum. Seventeen of 18 PGY-ls read the entire book, and all 30 PGY-2/3s read
      the book from cover to cover. Only 3 of 18 PGY-1 residents felt that the task of
      reading this book interfered with their work. More than 90% of the residents felt
      that reading the book clearly improved their attitudes toward the care of the
      terminally ill patient. Lessons learned from the book included all the humanistic
      qualities important in caring for the terminally ill and severely disabled.
      CONCLUSION: Well-chosen narratives of literature can be a powerful tool to learn
      attitudes and humanistic qualities in the care of the terminally ill.

PMID- 15859789
TI  - Culturally clueless: does it have to be terminal?

PMID- 15859784
TI  - Advancing educational scholarship through the End of Life Physician Education
      Resource Center (EPERC).

PMID- 15859790
TI  - Seeing the forest and the trees.

PMID- 15859791
TI  - USMLE and end-of-life care.

PMID- 15859792
TI  - A strategy for improvement in care at the end of life: the VA Faculty Leaders
      Project.
AB  - Given the commitment of the Veterans Health Administration (VA) to excellent,
      compassionate end-of-life and palliative care and the VA's extensive system of
      academic affiliations with the nation's medical schools, there may exist an
      opportunity to accelerate acceptance of state-of-the-art training for improved
      care for dying patients. Accordingly, the VA has initiated a project to develop
      strategies for implementation of benchmark curricula for end-of-life and
      palliative care. With the support of the Robert Wood Johnson Foundation, this
      initiative has been implemented in 30 internal medicine residency training
      programs affiliated with the VA nationally.

PMID- 15859793
TI  - Transforming end-of-life care for the 21st century: the hospice vision.
AB  - Hospice is recognized as the model for excellence in end-of-life care but its
      accessibility remains limited. A committee of the National Hospice Organization
      recently examined the barriers to hospice care and articulated a vision for
      quality end-of-life care for the 21st century. Its recommendations include public
      policy changes and other initiatives involving research, the education and
      practice of health professionals, the engagement of the public, and the operation
      of hospice programs.

PMID- 15859794
TI  - Establishing the right of the terminally ill to adequate palliative care: the
      litigation alternative.
AB  - The Bazelon Center For Mental Health Law in Washington, D.C., has undertaken a
      palliative care project to examine how litigation might be used to secure the
      rights of terminally ill patients to receive adequate palliative care, including
      the medications necessary to relieve the pain that often accompanies a final
      illness. One area of inquiry is the Medicare Hospice Benefit and the requirement
      that, to qualify for the benefit, a patient must have a prognosis of 6 months or
      less to live. A second major area of inquiry is regulatory restrictions on the
      prescription of opioids for pain relief of terminally ill patients and whether
      those restrictions improperly impede the physicians in their ability to engage in
      effective and appropriate pain management.

PMID- 15859795
TI  - Racial and income differences in use of the hospice benefit between the medicare
      managed care and medicare fee-for-service.
AB  - OBJECTIVE: To examine whether use of the Medicare Hospice Benefit between health
      maintenance organization (HMO) and Fee-For-Service (FFS)-enrolled beneficiaries
      varies by income or race. DATA SOURCE: Medicare enrollment and claims data for
      South Florida. RESULTS: In the FFS system, rate of death in hospice varied by
      income. In the HMO system, it did not. Time spent in hospice varied by income in
      the HMO system and not in the FFS system. There was little evidence that racial
      differences in hospice use differed between FFS and HMO options. CONCLUSIONS:
      These differences raise questions about whether some hospice use may be in
      response to system-level incentives.

PMID- 15859796
TI  - Family satisfaction and bereavement care following death in the hospital.
AB  - We conducted telephone interviews to assess family satisfaction with end-of-life
      care in the hospital and to gauge the extent of bereavement follow-up. We
      interviewed 53 relatives or close companions of adults who had died in our
      hospital within 5 to 12 months, representing 51 of the 153 families of English
      speaking patients who had experienced a nontraumatic, nonsudden hospital death
      over a 4-month period. Overall satisfaction with care and with communication was
      rated high on the Likert scale (mean 4.3, median 5 for both topics). However, we
      suggest that this commonly used quantitative evaluation method is inadequate for
      assessing family satisfaction with terminal care because simple, open-ended
      questions yielded an array of disturbing problems. We report on the major
      complaints of the bereaved, which primarily focused on respect for privacy,
      dignity, and comfort; communication with the family; emergency ward care;
      attention to advance directives; and bereavement support. We documented that
      commonly recommended bereavement services were lacking. Over a third of relatives
      reported no contact with hospital health professionals after the death, and over
      a quarter of contacts were patient-initiated. Most bereavement follow-up on the
      part of hospital staff seemed cursory or haphazard, rather than representing a
      serious and sustained attempt to assess or facilitate bereavement or identify a
      need for referral. Although 19% of respondents had sought professional help, none
      had been referred by their physician or the deceased's physician. Hospital-based
      social workers and chaplains played, at best, a minor role in bereavement follow
      up.

PMID- 15859797
TI  - Attitudes toward physician-assisted suicide among persons with multiple
      sclerosis.
AB  - This study was conducted to estimate the level of interest in assisted suicide
      among persons with multiple sclerosis (MS), the hypothetical conditions under
      which they would consider assisted suicide, and the factors associated with such
      interest. The sample of 511 members drawn from the Oregon and Michigan chapters
      of the National Multiple Sclerosis Society (NMSS) completed a mail questionnaire
      indicating whether they had ever considered assisted suicide, under what
      conditions they would consider it, and the correlates of considering assisted
      suicide. Close to one third of persons with MS in this study had thought about
      assisted suicide as an option for themselves. One quarter to one half would
      consider assisted suicide in five hypothetical circumstances, including
      experiencing unbearable pain, being unable to do things that made them happy,
      causing financial burden to caregivers or family members, or experiencing extreme
      emotional distress. Religiosity, social support, depressive symptomatology, MS
      symptoms, NMSS chapter, years since diagnosis, and gender were associated with
      some or all of the responses to the hypothetical conditions. The clinical and
      policy implications of these findings are discussed.

PMID- 15859798
TI  - Integrating palliative care into daily practice: a nursing perspective.
AB  - Education of health care providers has historically been based on the traditional
      model of curative care. In this model, the curative care focus suddenly ends,
      substituted by a palliative approach to care, too often only in the last hours of
      life. Patient goals and wishes may never be clearly established, leaving family
      and care providers to guess at what the patient's wishes were. If we are to
      provide quality palliative care, we must equate it with health care providers
      establishing, acknowledging, and honoring patient and family goals. A major
      facilitator in accomplishing palliative care goals can arise from the nursing
      assessment. This article reviews the elements of a comprehensive nursing
      palliative care assessment (PCA). Although this article focuses on nurses, it has
      application for all health care professionals. Completion of the PCA provides an
      opportunity for reflection and evaluation of personal practices that support
      integrating palliative care into the care of all patients diagnosed with a life
      threatening illness, beginning at the time of diagnosis and accelerating in
      intensity as the disease progresses.

PMID- 15859799
TI  - Decision making at the end of life: a model using an ethical grid and principles
      of group process.
AB  - Those who provide care for the dying seek to address issues of pain and suffering
      in the context of the psychological, spiritual, mental, and physical complexities
      of the individual experiencing a terminal illness. People who are dying are still
      living. They have the right to be in control of their lives. The staff
      (caregivers) also have an integrity which must be preserved. They too must be
      connected to the decision-making process. The reality of palliative care brings
      up unresolved psychological issues, often turbulent personal issues, for all
      involved in the process. This can cause extra unnecessary pain and suffering for
      all concerned. It is essential that a real (unflinching) and an ethical
      relationship between the patient and the staff be maintained and valued as these
      issues are confronted and resolved. This relationship will be subject to group
      process influences, which must be recognized and embraced. Avoidance of these
      issues can lead to unfairness, misunderstanding, shame, and lasting resentment
      among the caregivers, as well as to tragic consequences for the patient and the
      family. The purpose of this article is to describe a decision-making process in
      palliative care that includes the use of ethical principles as well as features
      of group process. The ethical grid was adapted and developed from the work of
      Jonsen, Siegler, and Winslade. The features of group process are based on
      theories of group work as defined by Trotzer; Johnson and Johnson; Gladding;
      Bion; Yalom; and Amundson, Borgen, Westwood and Pallard.

PMID- 15859800
TI  - Palliative radiation therapy.

PMID- 15859805
TI  - Euthanasia on television: dying Kevorkian style.

PMID- 15859810
TI  - Do not resuscitate orders: a call for reform.

PMID- 15859802
TI  - A different kind of bedside rounds.

PMID- 15859812
TI  - Advance care planning reconsidered: toward an operational definition of
      outpatient advance care planning.

PMID- 15859811
TI  - A failing grade for end-of-life content in textbooks: what is to be done?

PMID- 15859813
TI  - Analysis of symptom assessment and management content in nursing textbooks.
AB  - This article reports on one goal of a project designed to improve end-of-life
      (EOL) care in nursing education. The goal was to improve the content regarding
      pain and EOL care included in major textbooks used in nursing education. A
      descriptive study design was selected using content analysis of 50 texts selected
      from a potential of over 700 texts. The 50 texts included 45,683 pages. The text
      review was conducted using an analysis framework encompassing 9 essential areas
      of EOL care. The study methods included content analysis as well as
      quantification of the content present in the texts. The 9 areas of the analysis
      framework were: palliative care defined; quality of life; pain; other symptom
      assessment/management; communication with dying patients and families; role/needs
      of family caregivers in EOL care; death; issues of policy, ethics, and law; and
      bereavement. This article reports on the findings of the analysis related to
      symptom assessment/management. Nursing texts have limited content on symptom
      assessment and management. Increased attention to this area, a critical role of
      nursing, is essential to improved care for patients at EOL.

PMID- 15859814
TI  - The experience of life-threatening illness: patients' and their loved ones'
      perspectives.
AB  - BACKGROUND: Little is known about the actual concerns of patients and families
      regarding their health care during life-threatening illness and at end of life.
      Previous research with these groups has focused on their reaction to concerns of
      the medical community, eg, advance directives, decision making, and pain and
      symptom management. OBJECTIVE: To elicit and listen attentively to the actual
      experiences and major concerns of persons with life-threatening illness,
      personal/family caregivers, and bereaved individuals regarding their health care
      and interactions with healthcare system. DESIGN: Thirty-three focus groups were
      convened to involve 3 categories of individuals: persons with life-threatening
      illness (n = 77), personal/family caregivers (n = 70), and bereaved persons (n =
      81). Three focus groups, 1 of each kind, were held in 11 cities across the United
      States. Verbatim transcripts were coded and analyzed to identify themes. RESULTS:
      (1) Persons with life-threatening illnesses indicated that health professionals
      focus on medical and physical interventions, give too little information, appear
      uncomfortable talking about death, and do not include family members in
      conversations. (2) Caregivers reported exhaustion. They said that doctors do not
      appreciate the impact of the illness on their lives and rarely consult them,
      although all treatment decisions affect them. (3) Bereaved persons emphasized the
      loved ones' comfort in the last days of life. They wished that physicians would
      tell families when the end is near and avoid interrupting the process of dying
      with medical and often futile tasks. "I'm sorry" is sufficient initially to
      express the physician's condolences, but families appreciate contact weeks later.
      CONCLUSIONS: Many sources of dissatisfaction with care among persons with life
      threatening illness and their families are interpersonal in nature. The
      physician's respectful presence and demonstration of caring are highly desired,
      significant interventions for those who cannot be cured of illness and for their
      loved ones. Making healthcare professionals aware of these concerns may itself
      bring about some changes in daily practice. Further research is needed to test
      the most useful skills and behaviors of healthcare professionals in caring for
      persons with life-threatening illness and their loved ones.

PMID- 15859815
TI  - Family caregiving in cancer pain management.
AB  - The experience of cancer pain is known to greatly affect family caregivers as
      well as patients. There are many demands placed on caregivers of cancer patients
      with pain at home as a result of the shifting of care from the acute setting to
      the home. These complex demands significantly affect caregiver quality of life.
      The purpose of this study was to describe the experience of pain management from
      the perspective of family caregivers of patients with cancer amidst the current
      healthcare environment. This quasi-experimental study involved 231 family
      caregivers of patients with cancer pain receiving home care. Family caregivers
      were assessed in conjunction with a pain education program that provided patient
      and. family education regarding pain assessment, drug and nondrug interventions.
      Assessment measures used were the Quality of Life (QOL)-Family Caregiver Tool,
      Knowledge and Attitudes about Pain (K&A) Tool, and Caregiver Finances Tool. Study
      findings reveal disruption to family caregiver quality of life in the areas of
      physical, psychological, social, and spiritual well-being. There is also a
      continued need for education regarding cancer pain management. Comparison between
      patients and family caregivers demonstrates that pain impacts both the patient
      experiencing it and their caregivers.

PMID- 15859816
TI  - A medical resident inpatient hospice rotation: experiences with dying and
      subsequent changes in attitudes and knowledge.
AB  - PURPOSE: To evaluate intern experience in end-of-life care and self-assessed
      changes in attitude and knowledge, following a mandatory rotation on an inpatient
      hospice and in a nursing home. SUBJECTS AND METHODS: Twenty-seven interns
      enrolled in an internal medicine residency program completed a questionnaire
      examining experiences with dying patients, prior training in end-of-life care,
      and self-ratings of pertinent attitudes and knowledge. The questionnaire used a
      retrospective before and after design. Comparisons were evaluated using dependent
      two-tailed r-tests. RESULTS: Prior training was largely limited to undergraduate
      didactic courses. Few interns had received formal training in symptom management.
      Most felt poorly prepared to care for terminally ill patients. Eighty-two percent
      of interns had previously cared for a dying patient only in acute care. Fifty
      nine percent had never cared for a dying patient without intravenous fluids.
      Prior modeling of end-of-life care communication by attending physicians was
      uncommon. On a 5-point scale (strongly disagree-strongly agree) mean responses
      increased from 2.1 before-rotation to 3.0 after-rotation (p < 0.001) for the
      statement, "I feel as comfortable with a dying patient as I do with any other
      patient." Pain management knowledge increased from 2.0 before-rotation to 3.8
      after-rotation (p < 0.001). Seventy-seven percent strongly agreed with the
      statement, "some training in care of terminally ill patients should be mandatory
      for all internists." CONCLUSIONS: Prior experiences did not adequately prepare
      interns to deliver competent care. Significant improvements in attitude and
      knowledge were noted following the intervention. More hands-on clinical
      experiences in end-of-life care for residents are needed. Occasional didactic
      sessions will be inadequate.

PMID- 15859817
TI  - Opioid equianalgesic calculations.
AB  - Among the knowledge required by healthcare professionals to manage pain is an
      understanding of the differences between opioid agents and formulations. As the
      list of new opioid formulations continues to grow, it is increasingly important
      that clinicians understand the basic pharmacology of these analgesics and how to
      calculate equianalgesic doses. Administering an equianalgesic dose increases the
      likelihood that the transition to another opioid or route will be tolerated
      without loss of pain control or excessive side effects. Although calculation of
      equianalgesic doses requires relatively simple mathematical skills, few
      clinicians are prepared to compute them. The purpose of this article is to
      provide a basic review of the pharmacology of opioids, explain how to calculate
      an equianalgesic dose, and briefly describe some of the current controversies of
      the relative potencies of opioids listed in equianalgesic tables.

PMID- 15859819
TI  - Getting to Carnegie Hall: using standardized patients in palliative care
      education.

PMID- 15859823
TI  - The pedagogical use of discomfort.

PMID- 15859829
TI  - Revisiting the golden rule-medical student abuse.

PMID- 15859830
TI  - Statement on principles guiding care at the end of life.

PMID- 15859831
TI  - Surgery and palliative medicine: new horizons.
AB  - Despite important early contributions by individual surgeons to the hospice
      movement, the recent relationship between palliative medicine and surgery has
      been distant. The paucity of contributions from the surgical literature on
      palliative care and the lack of familiarity with surgical illness by palliative
      care practitioners signals a lack of preparation necessary to address many of the
      issues presented by chronic, incurable surgical illnesses. Remediation of this
      problem is possible through a planned, sequential program of interdisciplinary
      effort.

PMID- 15859832
TI  - The American Society of Clinical Oncology program to improve end-of-life care.
AB  - Too few cancer patients have optimal care at the end of life, as measured by
      unrelieved pain, death in a setting other than home, and uncoordinated care. The
      American Society of Clinical Oncology (ASCO), as the largest professional society
      whose members care for most cancer patients in the United States, has begun an
      initiative to improve end-of-life care. Educational programs for ASCO members
      have been started at the national level. A Task Force on End of Life Care was
      created to study the current state of end-of-life care, barriers to improved end
      of-life care, and what ASCO can do to improve end-of-life care. A member-wide
      survey has been completed to assess, from the professional's perspective, the
      current state of and barriers to end-of-life care. Specific sections of the Task
      Force will address hospice care, physician- assisted suicide, clinical barriers,
      economic barriers, research initiatives, educational deficiencies, and quality of
      care at the end of life. Improvements in end-of-life care can be made if the
      current deficiencies are noted, barriers ascertained, and specific solutions
      found. Professional societies have both the interest and responsibility to
      improve end-of-life care.

PMID- 15859833
TI  - When the patient dies: a survey of medical housestaff about care after death.
AB  - Our objectives were to determine medical housestaff exposure to the tasks of care
      after a death in the hospital and to characterize their practices, training, and
      attitudes toward this care. The study design was a review of hospital records and
      survey of housestaff at two academic medical centers. Forty-seven of 239 medical
      housestaff were surveyed. In one of the two hospitals studied, the number of
      death certificates completed by interns during 1 year was determined, and an
      estimate of exposure to hospital deaths and three other common discharge
      diagnoses during the same period was calculated. Housestaff were surveyed about
      the tasks of care after a death, including the determination of death,
      preparation of the body, notification of family, documentation, review of death
      with staff, and follow-up with family. Interns at one hospital completed a death
      certificate an average of 7 (range 1 to 13) times a year and were involved
      annually with approximately 30 inpatient deaths on ward teams. Exposure to a
      hospital death was comparable in frequency to that for pneumonia (48 cases/yr),
      congestive heart failure (32 cases/yr), or AIDS (24 cases/hr). Housestaff
      reported little or no formal training for the tasks of care after a death.
      Considerable variation among housestaff was noted in such routine tasks as how
      death was determined, discussions with the family, and providing bereavement
      care. Only 12% of respondents regularly reviewed personal reactions to a death
      with the medical team. In response to open-ended questioning, housestaff
      described significant distress and uncertainty regarding their roles in
      completing the tasks of care after a patient death. Medical housestaff are
      regularly exposed to hospital deaths, yet report minimal training, wide
      variations in practice, and significant distress with the performance of tasks
      after a death. We encourage greater attention to teaching about this important
      area of medical practice.

PMID- 15859834
TI  - Attitude and self-reported practice regarding hospice referral in a national
      sample of internists.
AB  - Systematic, nationally representative information about physicians' attitudes and
      behavior with respect to hospice care is not available. We sought to describe
      these previously unexamined attitudes and practices. We conducted a mail survey
      of a random national sample of 1311 internists, of whom 697 responded (an
      unadjusted response rate of 53%). We elicited physician's attitudes and self
      reported practice with respect to hospice. Most internists (89%) felt that
      hospice care was a good form of terminal care. Physicians with longer definitions
      of what constitutes "terminal" illness and those whose patients were more
      accepting of their prognoses were more likely to hold this opinion. Over the
      course of a year, the median internist referred five patients to hospice.
      Specialists and those with longer definitions of "terminal" were more likely to
      have done so. When asked "If you knew exactly how long a patient had to live, how
      long before death would you refer them to hospice?" the average response was 12.1
      +/- 8.5 weeks, but responses varied from 1 to 52 weeks, and the pattern of
      responses was bimodal, with one peak at about 13 weeks (73% of internists) and
      one at about 25 weeks (27%). Moreover, the distribution of hospice enrollment
      times implied by physician reports about ideal practice is significantly more
      compact than the distribution of survival that is actually observed; physicians
      support far fewer very short (<2 weeks) and very long (>6 months) stays in
      hospice than are observed. We conclude that internists show significant support
      for, and utilization of, hospice and they endorse a length of stay that is longer
      than currently observed. These findings suggest that it may be possible to
      increase both the number of patients using hospice and their duration of use of
      hospice.

PMID- 15859835
TI  - Clinical experience in hospice and palliative medicine for clinicians in
      practice.
AB  - Many healthcare professionals already in practice have identified their need to
      pursue further practical training in the provision of hospice and palliative
      care. We began offering a 1-week clinical experience to physicians, nurses,
      pharmacists, social workers, and chaplains in the summer of 1995. As of October
      1,1997, there have been 190 requests for application materials from individuals
      in more than 22 states, as well as from Singapore and Uganda. Thirty-five
      individuals completed visits by October 31,1997; 17 nurses, 16 physicians, 1
      psychologist, and 1 chaplain. Although all are working in areas related to
      palliative care, 57% (20 of 35) were not currently working for a hospice program.
      A 25-question examination was administered as a needs-assessment test. Overall
      they scored 75% correct. They did especially poorly on questions related to
      dosing of opioids, assessment of pain, and prognosis in AIDS. They completed a
      videotaped interview with a standardized patient focusing on skills in discussing
      a terminal prognosis, "do not resuscitate" (DNR) status, and hospice referral.
      They evaluated the entire educational experience with a self-report at the end of
      their visit using a Likert Scale with values of 1 to 5. To the statement "I
      achieved the specific goals which I set for myself," the average score was 4.6
      (range 1-5). To the statement "The experience was worth the time and effort," the
      average score was 4.9. To the statement "I would recommend this experience to
      others," the average score was 4.9. The evaluation was repeated 6 months after
      the visit with similar scores. In addition, to the statement "My current efforts
      are helping to change the way dying patients and their families are cared for in
      the broader environment in which I work," the average score was 4.9 (range 4-5).
      We conclude that this is a successful program of clinical exposure to hospice and
      palliative medicine for clinicians in practice.

PMID- 15859836
TI  - A community-based clinical selective in end-of-life care.
AB  - There is a widespread recognition among medical educators and accreditation
      organizations that medical students and young physicians lack the competency
      necessary to care for persons near the end of life. This article describes the
      institutional and attitudinal barriers to innovation in curriculum design. It
      then presents and evaluates a 1-month selective for fourth year students that
      focuses on providing end-of-life care to immigrant populations in community-based
      home hospice. The selective joined biomedical training in pain management and
      palliative care, a clinical rotation in home hospice care with an analysis of the
      way that social and ethnic factors inform and influence end-of-life care.

PMID- 15859837
TI  - A program of hospice and palliative care in a private, nonprofit U.S. Teaching
      hospital.
AB  - A hospice and palliative care program was established at Northwestern Memorial
      Hospital, a 773-bed private nonprofit hospital located in the urban center of
      Chicago. The program consists of three components: consultation service, acute
      inpatient unit, and home-hospice program. The consultation service saw an average
      of 57 new patients per month (range 45-80) in fiscal year 1997. The 12-bed acute
      care inpatient unit had an average midnight census of 9.8 in fiscal 1996. This
      decreased to 6.9 in fiscal 1997 due to new treatment approaches for AIDS and has
      rebounded to nine in the third quarter of fiscal 1998. The unit cares for more
      than one third of dying patients in the hospital. Patients do not have to access
      hospice insurance benefits to be admitted to the unit. The home-hospice program
      has a median length of stay of 31 days and serves patients living within the city
      limits of Chicago. A total of 800 patients were referred to the program, and 370
      patients died in the program in fiscal 1997. A total of 219 different physicians
      were attending physicians for patients in the program during a 3- year period.
      Revenue exceeded direct expenses by $1.48 million. Fee-for-service billing for
      physician services outside of those provided or billed under the Medicare Hospice
      Benefit are not included in these figures. The group practice that bills for the
      physicians collected an average of 50.5% of billed charges over 4 years. We
      conclude that a program of hospice and palliative care can be successful in a
      private teaching hospital in the United States.

PMID- 15859838
TI  - Radionuclide therapy for palliation of pain due to osteoblastic metastases.
AB  - Beta-emitting, bone-seeking radiopharmaceuticals, administered systemically,
      represent a good alternative or adjuvant to external beam radiotherapy for
      palliation of painful osteoblastic bone metastases. The most frequently used
      radiopharmaceutical for this purpose is strontium 89, followed by samarium 153
      ethylenediaminetetramethylene phosphonate, and infrequently phosphorus 32
      orthophosphate. Prior to consideration for radionuclide therapy, recent bone
      scans should be evaluated in order to determine if the patient has painful
      osteoblastic lesions likely to respond to therapy. Approximately 70% of patients
      with prostate and breast cancer will have a reduction in pain in response to
      radionuclide therapy, beginning within 2 to 4 weeks and lasting between 2 and 6
      months. Patients who are expected to live 3 or more months are more likely to
      benefit than patients with shorter duration life expectancy. Hematosuppression is
      the chief side effect of radionuclide therapy, with leukopenia and
      thrombocytopenia more likely to be clinically significant than anemia. Relative
      contraindications for treatment include osteolytic lesions, pending spinal cord
      compression or pathologic fracture, preexisting severe myelosuppression, urinary
      incontinence, inability to follow radiation safety precautions, and severe renal
      insufficiency.

PMID- 15859839
TI  - Pastoral care at the end of life: listening for the question beneath the
      question.

PMID- 15859841
TI  - When you don't have time to re-invent the wheel: evaluating educational materials
      for your own use.

PMID- 15859848
TI  - Assessing Oregon's physician-assisted suicide law: through a glass, darkly.

PMID- 15859850
TI  - Double effect: does it have a proper use in palliative care?

PMID- 15859849
TI  - The double effect of pain medication: separating myth from reality.
AB  - The principle of double effect is used to justify the administration of
      medication to relieve pain even though it may lead to the unintended, although
      foreseen, consequence of hastening death by causing respiratory depression.
      Although a review of the medical literature reveals that the risk of respiratory
      depression from opioid analgesic is more myth than fact and that there is little
      evidence that the use of medication to control pain hastens death, the belief in
      the double effect of pain medication remains widespread. Applying the principle
      of double effect to end-of-life issues perpetuates this myth and results in the
      undertreatment of physical suffering at the end of life. The concept of double
      effect of opioids also has been used in support of legalization of physician
      assisted suicide and euthanasia.

PMID- 15859851
TI  - Principle of double effect and end-of-life pain management: additional myths and
      a limited role.

PMID- 15859852
TI  - Physician experience caring for dying patients and its relationship to patient
      outcomes.
AB  - BACKGROUND: The quality of end-of-life care has become important to care systems
      and the public. No research has assessed how physician factors affect patient and
      family experience. OBJECTIVE: The objective of this study was to examine whether
      physicians' experience with dying is associated with differences in their
      patients' experiences while dying. METHODS: This was a prospective cohort study.
      Data were obtained from five geographically diverse teaching hospitals. The
      survey population was composed of 765 attending physicians who had at least one
      patient enrolled in a study of those with a high risk of dying. The patients were
      8203 hospitalized adults who were at least 80 years of age or had one of nine
      serious illnesses. The physician survey provided information about physician
      characteristics. Physician experience with death was stratified into five groups
      according to self-reported rate of dying patients in the physician's practice.
      Patient outcomes included pain, anxiety, depression, satisfaction with pain
      relief, presence and timing of do-not-resuscitate orders, concordance with their
      physicians about cardiopulmonary resuscitation, and hospital resource use.
      RESULTS: Oncologists and pulmonologists or critical care physicians had more
      frequent contact with death. Physician characteristics other than specialty were
      not associated with death experience. Compared with the physician group having no
      experience with death, the adjusted odds ratios for accord on resuscitation
      preferences were 1.38 (95% confidence interval [CI], 0.96 to 1.98), 1.47 (95% CI,
      1.03 to 2.11), 1.58 (95% CI, 1.10 to 2.26), and 1.64 (95% CI, 1.09 to 2.46) for
      the other four physician groups with progressively increasing experience. Other
      outcomes for patients were not associated with increasing physician experience.
      CONCLUSION: Most physicians have little experience with dying, and physicians'
      experience with death has little effect on patient outcomes. The concentration of
      experience in a small segment of physicians offers opportunities for targeting
      improvements in the care of dying patients, including physician education.

PMID- 15859853
TI  - Attitudes about end-of-life care: a national cross-sectional study.
AB  - BACKGROUND: Major concerns have been expressed about the preparation of
      physicians to provide end-of-life care. Little is known about how well academic
      health centers prepare students and residents to care for patients at the end-of
      life and about the values about end-of-life care transmitted by faculty. METHODS:
      In 1997, we conducted a telephone survey of a nationally representative sample of
      first-year medical students (n = 287), fourth-year medical students (n = 173),
      residents (n = 473), clinical faculty (n = 728), internal medicine residency
      training directors (n = 143), department chairs (n = 186), and medical school
      deans (n = 101) within U.S. academic health centers (response rate = 80.2%).
      RESULTS: U.S. medical students, residents and faculty evaluate themselves as
      inadequately prepared to provide end-of-life care. Academic health center
      constituents perceive that providing care at the end of life requires medium to
      high levels of expertise. Academic health center constituents are divided about
      whether responsibility for providing care at the end of life rests with
      generalists or with specialists and view managed care as nearly equivalent to the
      fee-for-service sector in its capacity to provide excellent end-of-life care.
      CONCLUSIONS: Academic leaders and faculty, as well as their students, lack
      confidence in their own skills in providing end-of-life care. They also question
      the ability of the current and evolving health care delivery system to provide
      excellent end-of-life care.

PMID- 15859854
TI  - Reciprocal suffering: the need to improve family caregivers' quality of life
      through palliative care.
AB  - There is growing recognition of the reciprocity of suffering by patients and
      families experiencing terminal illness and the need to improve the quality of
      their lives as the patient's illness progresses. Research is presented that
      addresses the importance of a dyadic perspective in recognizing patients' and
      families' stress and adjustment and the related physical, emotional, social,
      spiritual and financial needs at the end-of-life. These aspects of quality of
      life are specifically addressed by palliative care. The philosophy and goals of
      palliative care are described, as is its role in promoting the best possible
      quality of life for patients and their families experiencing terminal illness.
      This article addresses the importance of assessing the dynamics of the family
      caregiving system and potential palliative care interventions to enhance the
      quality of life of family caregivers. Implications for research are also
      discussed.

PMID- 15859855
TI  - The Medicare hospice benefit's influence on dying in nursing homes.
AB  - For dying nursing home residents, the prevalence of symptoms and care utilization
      prior to death has yet to be empirically described for a population-based sample.
      Yet, related work has suggested that the quality of care for dying nursing home
      residents is less optimal. The provision of Medicare hospice care in nursing
      homes offers a means for improving terminal care in nursing homes. However, other
      than controversial findings emanating from the U.S. Office of Inspector General's
      (OIG's) hospice studies, there is a dearth of evaluative research on the
      comparative costs and the benefits of Medicare hospice care in nursing homes. In
      this article, we discuss current knowledge concerning the dying experience of
      nursing home residents and of the influence of the Medicare hospice benefit in
      nursing homes. In doing so, we critique the OIG's study of hospice care in
      nursing homes and we raise concerns regarding access to the Medicare hospice
      benefit in nursing homes. We conclude by delineating the research needed to more
      fully understand the dying experience of nursing home residents and the influence
      of Medicare hospice care provision on this experience.

PMID- 15859856
TI  - Improving cancer pain management through a system wide commitment.
AB  - Despite the well documented need for better cancer pain management there is
      little evidence that conventional educational approaches have improved clinical
      practice. This article discusses strategies to improve cancer pain management,
      focusing particular attention to institutional approaches that contain quality
      assurance (QA) and quality improvement (QI) efforts. An innovative pain
      management project is described that includes an in-depth evaluation of system
      and provider strengths and weaknesses; a system-wide commitment to cancer pain
      management; patient/family, nurse, pharmacist, and physician collaborative teams;
      use of a Washington State law allowing pharmacist prescriptive authority of
      narcotics and other drugs within a prescribed treatment protocol; and QA and QI
      efforts to improve and document performance. The authors strongly believe that
      the development of collaborative programs that integrate the power of the
      institutional process with clinical care will produce the greatest improvement in
      patient care not only for cancer pain, but also for other difficult domains of
      end-of-life.

PMID- 15859857
TI  - Caring for patients at the end of life in an HMO.
AB  - BACKGROUND: Increasing numbers of Americans are receiving care within managed
      care organizations (MCOs), and the ability of MCOs to provide high-quality end-of
      life care is under greater scrutiny. Although many anecdotal reports have been
      published, almost no research has been published on patient/family experiences
      with end-of-life care in MCOs. METHODS: We undertook a qualitative study of end
      of-life care during 1996 and 1997 in the closed-panel staff-model, not-for
      profit, health center division of Harvard Pilgrim Health Care. We collected and
      analyzed data from five focus groups composed of family members of patients who
      had died during the preceding year (n = 22) and four focus groups composed of
      clinicians and administrators who routinely care for dying patients and/or have
      responsibility for managing end-of-life care resources and systems (n = 31).
      RESULTS: Problems noted in this setting that are also reported in other health
      care settings included divergent expectations and unclear primary care/specialist
      roles and hospice/primary physician roles, difficulties in transitions across
      care settings, ineffective communication between physicians and patients/families
      about end-of-life care preferences, and lack of systematic attention to
      bereavement care. More unique to managed care settings were problems related to
      the absence of a consistently applied hospice benefit and concerns about the
      impact of cost containment on the quality of care, reflecting the conflict
      between the dual roles of MCOs as both insurers and providers of care.
      CONCLUSIONS: Our findings highlight specific issues involved in providing quality
      end-of-life care in MCOs and suggest areas for further exploration.

PMID- 15859858
TI  - End-of-life physician education: is change possible?

PMID- 15859859
TI  - Death education: a play in three acts.

PMID- 15859863
TI  - Teaching physicians to deliver bad news: some practical advice.

PMID- 15859867
TI  - Spousal illness burden is associated with delayed use of hospice care in
      terminally ill patients.
AB  - Patients' families are important in hospice not only because they themselves
      might benefit from it, but also because they influence whether and how hospice is
      used to begin with. We hypothesized that, among the married, people with less
      capable spouses (in this case, those who are less healthy) should be less able to
      use home hospice care and should enroll in hospice later in the course of their
      illness, closer to death. We tested this hypothesis by evaluating the impact of
      spousal health on the timing of patients' use of hospice in a select group of 517
      couples, a total of 1034 patients, for whom we have health data for both partners
      from Medicare claims records. We evaluated cohort survival using the Kaplan-Meier
      method and Cox regression, and we measured illness burden using the Charlson
      comorbidity score. Among the probands, 45.6% had a primary cancer diagnosis,
      44.5% were female, 7.5% were nonwhite, their mean age was 80.0 years (+/-7.6 SD),
      and their mean Charlson score was 3.1 +/- 3.0. The probands' median survival
      after hospice enrollment was 55 days. Spouses were similarly composed
      demographically, but were less likely to have a cancer primary diagnosis (35.4%
      had cancer) and were slightly younger than the probands; their mean Charlson
      score was 2.9 +/- 2.9. Each additional point in the Charlson score of the spouse,
      controlling for measured characteristics of the proband, is associated with a
      5.1% increase in the risk of death after enrollment. That is, after controlling
      for the characteristics of hospice patients themselves, those with sicker spouses
      are enrolled later. Compared with patients with the healthiest spouses, those
      with moderately sick and very sick spouses had considerably later enrollment into
      hospice, with the median survival decreasing from 111 to 49 to 22 days across the
      groups. Our data suggest that there may be a separate role of spousal health in
      affecting the time of hospice enrollment, and that patients' social support may
      affect not just their health status to begin with, but also their use of health
      care in general.

PMID- 15859868
TI  - Improving end-of-life care education in home care.
AB  - A training program for home care professionals, HOPE (Home care Outreach for
      Palliative care Education), was designed to improve the knowledge and skills of
      those providing care to patients and family caregivers at home. This article
      presents an overview of the pilot HOPE training program and a case study to
      illustrate the complex end-of-life (EOL) care needs in nonhospice home care
      settings. HOPE was designed as five training modules based on a needs assessment
      survey completed by 134 home care agencies. The training modules were composed of
      (a) General Overview of End of Life Care; (b) Pain Management; (c) Symptom
      Management; (d) Communication with Patients and Families; and (e) the Death
      Event. The program was implemented for clinical staff (N = 52), predominantly
      nurses, in two home care agencies and evaluated with pre- and postcourse surveys.
      Pre- and postcourse evaluations demonstrated an increase in the overall rating of
      EOL care from a mean rating of 5.97 to 7.42 for self-assessment and from 6.59 to
      7.94 for agency assessment (on a scale of 0 = not at all effective to 10 = very
      effective). Future palliative care education should also include evaluation of
      the impact of such programs on patient care. We concluded that increasing
      palliative care knowledge of home care professionals is necessary to improve
      patient care at the EOL.

PMID- 15859869
TI  - Attachment/detachment: forces influencing care of the dying in long-term care.
AB  - Death occurs among older adults in institutions more often than at home with
      family and friends. The older people are, the more likely they are to die in a
      nursing home. The purpose of this study was to describe staff and administrator's
      perspectives on death and dying in long-term care and to explore problems in
      providing humane care to dying residents that fosters gentle closure to life.
      Using focus group interviews as the primary data collection method, 22 focus
      group sessions were conducted in 11 nursing homes. Separate group sessions were
      held for staff and administrators in the nursing homes. The core variable
      identified in this study was the attachment of staff to residents in long term
      care. Attachment enhanced the quality of terminal care and fostered a gentle
      closure to life. Mediating forces influencing the process of attachment were
      identified as individual forces, as well as forces internal and external to the
      nursing home.

PMID- 15859870
TI  - A faculty development course for end-of-life care.
AB  - A faculty development course was offered at the Medical College of Wisconsin to
      bolster existing medical student and housestaff training opportunities in
      palliative medicine. An 8- week, 12 contact-hour course was designed to provide
      up to 15 faculty members training in the practice and teaching of end-of-life
      care. Fifteen faculty registered, but only 10 attended at least three of eight
      educational sessions. Educational formats included didactic presentations, case
      studies, study guides and completion of action plans-explicit plans for
      utilization of newly learned material in clinical and educational practice. In a
      retrospective, pre/post self-evaluation, participants indicated poor or fair
      precourse knowledge and self-confidence in most areas of end-of-life care.
      Significant improvement in end-of-life knowledge and selfconfidence was noted for
      eight of 11 content areas and in self-assessed education skills in six of seven
      content areas. Although attendance was disappointing, the course was strongly
      endorsed by participating faculty. Faculty who attended at least three sessions
      reported significant improvement in many aspects of end-of-life clinical care, as
      well as in self-confidence and education skills, and were able to use the
      educational material to train a range of learners. Sample educational material is
      included with this report.

PMID- 15859871
TI  - Prospective evaluation of referrals to a hospice/palliative medicine consultation
      service.
AB  - A hospice/palliative medicine consultation team was formed in July 1993 in a U.S.
      teaching hospital to provide patient care and education. The team consists of an
      attending physician, nurse, fellow, and any residents or medical students
      rotating on the service. More than 500 consultations are received each year.
      Beginning in January 1995,108 consecutive referrals to the service were assessed
      using a standard form completed by the nurse. The average age was 62 years. The
      gender of patients was 58% male and 42% female. At the time of consultation 87%
      were hospitalized on general medical services (including hematology/oncology), 4%
      were on surgical services, 3% on the neurology service, and 6% were in an
      intensive care unit. Cancer was the primary diagnosis in 52%, AIDS in 24%, with
      the rest being distributed among cardiac, renal, pulmonary, neurologic, and other
      diseases. The most prominent physical symptoms were 48% weakness/malaise, 44%
      pain, 28% dyspnea, and 23% agitation/confusion. The average length of time
      patients were followed was 2 days (range 1-10). We conclude that a
      hospice/palliative medicine consultation service sees a broad range of patients
      and problems and is a rich resource for teaching hospice and palliative medicine.

PMID- 15859872
TI  - A review of oral transmucosal fentanyl citrate: potent, rapid and noninvasive
      opioid analgesia.
AB  - The physiochemical characteristics of the potent synthetic opioid agonist
      fentanyl make it ideal for noninvasive transmucosal delivery. Studies of oral
      transmucosal fentanyl citrate (OTFC), a candied matrix formulation administered
      orally as a palatable lozenge on a stick, have investigated and determined this
      analgesic's pharmacokinetics and pharmacodynamics in a number of clinical
      settings, including premedication before surgery, acute analgesia for painful
      medical procedures, and, most recently, for the control of breakthrough cancer
      pain. The onset to meaningful pain relief in patients with acute pain from
      surgery or breakthrough pain from cancer is between 5 and 10 minutes after
      initiating OTFC use, equivalent to intravenous morphine. Analgesic dose
      equivalency studies suggest that OTFC is, on average, about 10 times more potent
      than morphine, although, in randomized, controlled, and blinded studies, many
      patients who were using relatively high doses of opioid anlagesics on an around
      the- clock schedule for control of cancer pain reported that even a low dose of
      OTFC (i.e., 200 microg) provided adequate relief from breakthrough pain. Side
      effects from OTFC are similar in character and frequency to other opioids,
      including sedation, nausea, and pruritus. These effects appear to wane rapidly
      with repeated use of this medication. To date there have been no reported serious
      adverse events in any of the population groups studied or treated with OTFC.

PMID- 15859873
TI  - Management of malignant bowel obstruction in advanced cancer: a brief review.
AB  - Malignant bowel obstruction is an odious complication of numerous malignancies,
      most notably ovarian and colorectal cancers. It reduces quality of life and
      promotes considerable physical and emotional suffering, precluding a peaceful and
      comfortable death and deterring appropriate familial bereavement. Palliative
      management of bowel obstruction includes operative and nonoperative strategies,
      with therapeutic selection based on patient preference and anticipated life
      expectancy. Available therapies include laparotomy, enteral intubation,
      intravenous and subcutaneous hydration, parenteral nutrition, and pharmacologic
      agents.

PMID- 15859874
TI  - What is palliative care?

PMID- 15859877
TI  - Alternatives to lecturing.

PMID- 15859875
TI  - An emerging respect for palliative care in radiation oncology.

PMID- 15859883
TI  - Do we need a new specialty?

PMID- 15859885
TI  - Psychiatric aspects of excellent end-of-life care: a position statement of the
      Academy of Psychosomatic Medicine.

PMID- 15859884
TI  - Precepts of palliative care.

PMID- 15859886
TI  - An anatomy memorial tribute: fostering a humanistic practice of medicine.
AB  - Medical students' first "patients" are the individuals who donate their bodies
      for laboratory dissection, and these first lessons of medicine serve as a model
      for the doctor-patient relationship. An Anatomy Memorial Tribute was initiated by
      students at Mount Sinai School of Medicine to honor these donors. Students and
      faculty shared music, art, and readings of original poetry and prose. The event
      facilitated dialogue about attitudes and feelings with regards to death and
      dying. Controversial issues included anonymity versus identification of donors
      and the appropriateness of professionals showing emotion in public. The feedback
      from both students and faculty participants in the event was overwhelmingly
      positive. Students wrote that the tribute provided a sense of closure for their
      dissection experience and reinvolved them in shaping their education; faculty
      indicated that it was appropriate. Memorial tributes are a first step toward
      fostering the personal growth and emotional preparation required for competent
      and compassionate patient care. To encourage a humanistic approach to medical
      education, faculty have the opportunity to participate in such tributes,
      facilitate sensitive use of language in the anatomy laboratory, and expand the
      broader medical school curriculum in relation to death and dying. Medical
      students may expand the concept of memorial tributes and enhance their
      professional growth in this area by sharing information, ideas, and experiences
      through national organizations such as the Humanistic Medicine Group of the
      American Medical Students Association. The capacity of physicians to effectively
      serve patients facing the end of life is particularly relevant in the setting of
      palliative medicine.

PMID- 15859888
TI  - Hospice: 15 years and beyond in the care of the dying.

PMID- 15859887
TI  - The hospice medicare benefit: an appraisal at 15 years-introduction to a series.

PMID- 15859889
TI  - The medicare hospice benefit-15 years of success.

PMID- 15859890
TI  - The medicare hospice benefit: a critique from palliative medicine.

PMID- 15859891
TI  - Hospice: does it still save medicare money?

PMID- 15859892
TI  - Payment code for hospital-based palliative care: help or hindrance?

PMID- 15859893
TI  - Hospice and palliative care: a parting of ways or a path to the future?

PMID- 15859894
TI  - Delirium, confusion, and agitation at the end of life.

PMID- 15859895
TI  - The coevolution of bioethics and the medical humanities with palliative medicine,
      1967-1997.
AB  - The Department of Humanities that I chair at the Pennsylvania State University
      College of Medicine was the first such department ever established at any medical
      school. It opened in 1967. In that same year, St. Christopher's, the first modern
      hospice, opened in London. Merely a coincidence? I do not think so. The forces
      that propelled bioethics and the humanities into medical education were the same
      forces that called the modern hospice movement into being. Over the past three
      decades, both movements have evolved together, nourishing each other and
      challenging each other. This essay will sketch three phases in the coevolution of
      bioethics and the medical humanities on the one hand, and hospice and palliative
      medicine on the other. The first phase I will call the common matrix of concern.
      The second phase I will call the elaboration of the concept and practice of
      "whole person care." The third phase I will call the era of public policy and
      corporate medicine.

PMID- 15859896
TI  - Vigils, versed, and ice castles.

PMID- 15859897
TI  - Medical story-telling as a teaching tool in palliative care education.

PMID- 15859901
TI  - Xenotransplantation: a view to the past and an unrealized promise to the future.
AB  - Since the early 20th Century when Emerich Ullman transplanted a pig kidney into
      the arm of a woman (1902), Princeteau implanted portions of a rabbit kidney into
      the kidney of a child who was dying of renal insufficiency (1905), Jaboulay
      transplanted two kidneys from a pig and a goat as donor sources (1906), and Unger
      implanted a monkey kidney into a human (1910), xenotranplantation has made some
      strides, mostly related to advanced surgical techniques, improved knowledge of
      immunological principles, and to steps associated with the development of the
      most effective immunosuppressive therapy. Innovative surgical techniques were
      introduced by Alexis Carrel in the first decade of the 1900s, so that vascular
      anastomoses could be realized without a considerable amount of thrombotic/embolic
      problems, long before heparin times. Inasmuch as these advances were soundly
      characterized, it became evident that the results were far from expected and that
      the time was not ripe for xenotranplantation. It took 50 years (1963) before
      Keith Reemtsma transplanted 13 kidneys from chimpanzees into patients with kidney
      failure. Remarkably, one patient survived for 9 months before dying from
      electrolyte imbalance. In the ensuing years, Starzl (1964), Hardy (1964), Cooley
      (1968), Ross (1968), Barnard (1977), Bailey (1984) and a few others entered this
      new field with less than satisfactory accomplishments. The unsolvable barrier of
      hyperacute rejection required persistence and ingenuity. The recognition of
      xenoantibodies and their requirement for full depletion, through ex vivo porcine
      perfusion, plasmapheresis, immunoabsorption and complement inhibition,
      facilitated important advances in this field. The introduction of accommodation
      and molecular chimerism has further improved the knowledge of this newly
      conceived field. Advanced molecular engineering techniques have recently
      permitted the creation of the clonal Gal-deficient pig by eliminating the alpha
      1, 3 galactosyltransferase gene. These discoveries together with better
      immunosuppression raise hope for the yet unrealized promise of
      xenotranplantation.

PMID- 15859902
TI  - Sirolimus: a current perspective.
AB  - Sirolimus, a macrocyclic lactone that displays a novel mechanism of
      immunosuppressive action, is a critical-dose drug requiring therapeutic drug
      monitoring for optimal outcomes. The compound was documented in two multicenter,
      blinded clinical trials to reduce the incidence of acute rejection episodes when
      used in combination with cyclosporine and steroids vs. azathioprine or placebo
      comparators. Furthermore, studies utilizing cyclosporine withdrawal documented a
      long-term benefit on renal function of chronic sirolimus therapy, albeit with a
      modestly enhanced incidence of acute rejection episodes. Although this
      application may be useful in selected cases, we believe that minimal initial
      cyclosporine exposures de novo mitigate the need for eventual withdrawal for
      chronic nephropathy, while preserving the immunosuppressive synergy during the
      maintenance phase. Recipients treated de novo with a sirolimus-cyclosporine
      combination tolerate steroid withdrawal at 1 month after living-donor or at 3 to
      6 months after cadaveric kidney transplantation with only a 5% risk of acute
      rejection episodes and 6% incidence of chronic reactions within 3 years. However,
      sirolimus exacerbates the hypertriglyceridemic and hypercholesterolemic
      proclivities of transplant recipients, as well as exerts myelosuppressive
      effects, which are augmented by concomitant therapy with azathioprine or,
      particularly, with mycophenolate mofetil. Due to its apparent lack of
      nephrotoxicity, sirolimus has been employed for induction therapy in a
      calcineurin antagonist-free regimen in combination with either basiliximab or
      rabbit antilymphocyte sera for weak or strong immune responders, respectively,
      followed by introduction of a calcineurin antagonist upon resolution of the
      ischemia-reperfusion injury. Therefore, sirolimus proffers a potent and unique
      platform for new immunosuppressive strategies in organ transplantation.

PMID- 15859903
TI  - The relationship between HLA typing and HCV infection and outcome of renal
      transplantation in HCV positive patients.
AB  - The role of Human Leukocytic Antigen (HLA) antigens in susceptibility to
      Hepatitis C Virus (HCV) infection is still being debated. We analyzed HLA
      phenotype frequencies in two major ethnic groups, namely Egyptian and Saudi
      nationals. The Egyptian group included 110 patients of whom 55 were HCV positive
      and the other 55 HCV negative (control group). The Saudi group included 146 HCV
      positive patients and 122 HCV negative individuals (control group). The results
      for the Egyptian population revealed increased frequencies of some HLA phenotypes
      and decreased frequencies of others but without any statistically significant
      difference. In contrast, in the Saudi population, the HLA-A19 phenotype was
      significantly increased in HCV positive patients when compared with the control
      group while significantly decreased frequencies were found for HLA-B8, HLA-DRI
      and HLA DR3. Our data suggest that there was no significant association between
      HLA phenotypes and susceptibility to HCV infection among the Egyptian population
      while the overall data of the Saudi population seem to indicate that the
      expression of particular HLA alleles could be associated with susceptibility or
      resistance to the HCV infection. Further studies on larger numbers of patients
      are needed to support the role of the HLA system in HCV infection. A total of 108
      HCV positive patients underwent renal transplantation at the Jeddah Kidney Center
      and the results were compared with 100 age and sex-matched controls. Graft
      survival at 36 months was 82% and 86% for HCV positive and control subjects
      respectively while patient survival was respectively 90% and 91%. Our data
      suggest that the outcome, at least in the Short-time, of renal transplantation in
      HCV positive patients is very good.

PMID- 15859904
TI  - Recent developments and future prospects in pancreatic transplantation.
AB  - Pancreas transplantation is not a life-saving procedure, so the benefits should
      be sufficient in terms of quality of life to outweigh the risks. Successful
      transplants give patients more positive health perceptions, improved social
      interaction, more satisfaction with diet and increased vitality. Studies are
      unanimous in finding that patients with successful transplants rate their lives
      better after transplantation than before. The effect of a double transplant in
      uraemic diabetic patients can be dramatic; patients rate their quality of life
      higher than diabetics who receive a kidney transplant alone.

PMID- 15859905
TI  - Chronic rejection: prospects for therapeutic intervention in fibroproliferative
      vascular disease.
AB  - Vascular disease, manifesting as either transplant arteriopathy or native
      atherosclerosis, is currently the main obstacle to successful transplant outcome.
      In addition, vascular restenosis following balloon angioplasty or stenting
      continues to limit the long-term efficacy of these procedures. Neointimal
      hyperplasia is refractory to conventional immunosuppression although newer
      agents, such as rapamycin, have shown considerable promise in controlling it. By
      allowing large-scale study of gene expression during vascular remodelling, the
      emerging field of genomics is poised to revolutionise the drug discovery process.
      Here we summarise our initial experience using genomic methods to identify new
      targets for therapeutic intervention in vascular disease.

PMID- 15859906
TI  - Noncompliance with immunnosuppressive medications after renal transplantation.
AB  - Noncompliance with immunosuppressive medications in renal transplant recipients
      results in higher rate of acute rejection episodes, allograft dysfunction, graft
      loss and patient death. We studied incidence and risk factors of medications
      noncompliance in 286 renal transplant recipients who were consecutively seen in
      our renal transplant clinic between February and April 2002. One hundred and
      seventy were male, 116 female. Their age ranged from 12 to 70 years (mean 39.1+/
      11.6). The length of time since the date of transplantation ranged from 5 to 231
      months (mean 76.7+/-53.5). The results of study showed that 70 patients (24.5%)
      to be noncompliant (7.7% noncompliant minor and 16.8% noncompliant major). The
      time since the date of transplanation was a significant risk factor in both
      noncompliant minor and major groups (P<0.001 and P<0.001). The other risk factors
      associated with major noncompliance was young age (P<0.001), lower level of
      education (P<0.01), lower socioeconomic class (P<0.05), addiction and psychiatric
      disorders (P<0.05). Transplant recipients with major noncompliance also had more
      acute rejection episodes (P<0.001) and allograft dysfunction (P<0.01). We
      conclude that noncompliance with immunosuppressive medications is very common in
      renal transplant recipients and it results to significant acute rejection
      episodes and allograft failure.

PMID- 15859907
TI  - Conversion from tacrolimus to cyclosporine--a based immunosuppression following
      liver transplantation.
AB  - We examined the frequency, reasons and outcome after conversion from Tacrolimus
      to Cyclosporine A. From August 1989 to December 1992, 1000 consecutive liver
      transplantation patients were studied, which included 834 adults (age>18 yr.) and
      166 children with mean follow-up of 77 months (range 56 to 96). A prospectively
      populated electronic database was queried to identify patients that underwent
      conversion, the clinical indication and outcomes. Thirty-seven out of 834 adult
      recipients (4.43%), mean age of 48.4+/-12.9 years, 19 male (51.35%) and 18
      females (48.64%) required conversion from Tacrolimus to Cyclosporine A baseline
      immunosuppressive therapy. No pediatric patient required conversion. The mean
      time interval from liver transplantation to Cyclosporine A conversion was
      443.45+/-441.44 days (range 22 to 1641). The clinical indications for conversion
      included: 20 neurological (54%), 6 gastrointestinal (16%), 5 hematological (14%),
      and 6 other (16%) scenarios. Seven of the 37 patients (18.9%) died. The causes of
      death were multi-organ failure (2), sepsis (2), pancreatitis (1), hepatic failure
      due to relapse of ethanol abuse (1), and unknown cause (1). Nine out of 37
      patients (24.32%) had to be reconverted to Tacrolimus (mean 282.22+/-499.79 days;
      range 15 to 1583 day with a median of 135) after institution of Cyclosporine A;
      none showed recurrence of the original symptoms. The reasons for these re
      conversions were acute cellular rejection (44%, n=4), chronic rejection (11%,
      n=1), increased hepatic enzymes (33%, n=3) and progressively worsening
      neurological symptoms (11%, n=1). The frequency of conversion from Tacrolimus to
      Cyclosporine A was 4.43%. Conversion is safe and efficacious if done in a
      controlled setting. Additionally, re-conversion to Tacrolimus for lack of
      efficacy of Cyclosporine A did not appear to be associated with a recurrence of
      the condition that caused the initial switch.

PMID- 15859908
TI  - HLA-matching by DNA methods: impact on a living related renal transplantation
      programme.
AB  - DNA methods have resulted in improved renal allograft survival rates in cadaveric
      renal transplantation. This paper describes the impact of DNA typing by PCRSSP on
      a living related renal transplant (LRRT) programme. It evaluates error rates in
      serology, acute rejections, graft function and survival rates between the two
      typing methods. Serological typing was done on CTS 120 antisera Class 1 and 60
      antisera Class 2 and 72 antisera Terasaki Class1 and 72 antisera Class2 Antigens.
      Low resolution PCR-SSP typing was done by 24 primers for HLA A , 48 for HLA B and
      24 for HLA DR. Of the 585 transplants, 159 (Group I) were serology based, 172
      serology and PCR-SSP for HLA DR (Group II) and 254 on serology and PCR-SSP for
      HLA A and B and only PCR-SSP for HLA DR (Group III). Error rates in serology as
      compared to PCR-SSP were 24% for HLA A, 16% for HLA B and 35% for HLA DR. Acute
      rejection in Group I were 39% Group II 30% and Group III 26% (p 0.02). Graft
      function of serum creatinine<1.5 mg/dl at 1 year was found in 26% of Group I
      patients as compared to 48% of Group III (p<0.0001). One and three year graft
      survival was 93% and 87% for Group II as compared to 81% and 69% for Group I
      respectively (p 0.0001). Matching by this combination of serology and PCR-SSP is
      not only economical for a developing country but also improves graft survival by
      12% at 1 and 18% at 3 years.

PMID- 15859909
TI  - Infection related renal impairment: a major cause of acute allograft dysfunction.
AB  - We prospectively analyzed the impact of post-transplant infections on the renal
      function in 532 stable renal transplant recipients (M=340; F=192) over a period
      of 5 years. Their age ranged from 3-75 years (40+14 years). During the follow-up
      period, 52 patients expired and 64 lost on followup. We defined renal impairment
      (RI) as a persistent rise in serum creatinine above 20% from baseline value. 495
      episodes of RI occurred in 269 recipients. This included 180-36% episodes of
      acute rejection, 53-10.7% Cyclosporine toxicity, 236-47.7% infection related
      renal impairment [IRRI] and 26-5.3% others. The severity of renal failure is less
      in IRRI (100+90.2) than that of acute rejection (166+127.1), but was more than
      that in cyclosporine toxicity (50+42.2). Sites of infection in IRRI were urinary
      (33%), respiratory (26.3%), septicemia (15.7%) and others (25.4%). Episode of
      IRRI occurred more frequently in LURD (159-67.4%) compared to LRD-RTR (50-21.2%).
      Occurrence of IRRI is more significantly higher in patients on triple drug
      immunosuppression (IS) (34.3%) than those on two drug IS (13.2%) (P=or<0.01).
      Ecoli (23.1%), Pseudomonas (11.1%), Salmonella (8.8%), Klebsiella (8.8%) and
      Staphylococai (8.3%) were the major organisms producing IRRI. IRRI is frequent
      (27.8%) during the first six months. Present study denotes that IRRI is a major
      cause of acute failure in RTR.

PMID- 15859910
TI  - The generics in transplantation and the rules on their use.
AB  - By definition a product identified by its official chemical name rather than an
      advertised brand name is called a generic. If a drug exert its pharmacological
      effects at the same site, have the same potency, same dosage form and same
      bioavailability as a brand name, reference listed drug (RLD), is considered as a
      generic. However inactive ingredients can differ between brand name and generic.
      It is through the regulations of the FDA that the generics gained many ground in
      the drug market, they currently account to more than 42% of the total
      prescription in the USA. These regulations include the abbreviated new drug
      application (ANDA) for the registration process and drug substitution at the
      pharmacy level without patient or physician consent. This coupled with a keen
      interest of third party payers and the health authorities to reduce the high
      transplant health budget (over 2 Billion US $) made it a necessity to introduce
      the generics into the field of transplantation. Using the above mentioned
      definition we can theoretically say that all anti-lymphocytes, produced in the
      same animal species, are generic of each. Moreover, monoclonal antibodies that
      are directed against the same target and have the same bioavailability are also
      consider generics to each other. Of all the immunosuppressive drugs that have
      been introduced into the field of transplantation none has been as dominant as
      Cyclosporine. Cyclosporine became and still is the backbone for any
      immunosuppressive protocol. In the year 1992, Consupren, the first, non-FDA
      approved, generic to Sandimmun was introduced. Although Consupren was not
      bioequivalent to Neoral, however, long-term results in kidney transplantation
      have been similar for both drugs. The introduction of Consupren resulted in a
      near 40% reduction in the total cost of immunosuppressive therapy. Interestingly
      the cost of the brand name drug Neoral was also reduced by 20%. The cost
      reduction allowed the introduction of the new immunosuppressive agents MMF and
      Rapamycin. Currently there are 5 FDA approved Cyclosporine generics with a 20%
      market share in the USA and a mere 0% in Europe. Alternatives formulations to
      both Rapa and for MMF would be available soon. These forms are not by definition
      generics and are considered by the FDA to be new brand names act on the same site
      as Cell Cept and Rapaimmune. Their introduction would be a great welcome and
      would definitely results in cost saving in transplantation cost. In conclusion,
      generics efficacy and safety is similar to that of the brand name and their use
      is cost effective.

PMID- 15859911
TI  - Graft and quality of life outcomes in older recipients of a kidney transplant.
AB  - BACKGROUND: It is well recognized that kidney transplants significantly improve
      quality of life for patients with end-stage renal disease (ESRD). This benefit is
      not as clearly documented for older recipients as it is for younger recipients.
      We looked at outcomes, both medical and psychosocial, in a group of older (> or
      =65 years) kidney transplant recipients and compared the results to a group of
      younger recipients (18 to 64 years). METHODS: From 1990 through 2002, we
      performed 2,746 kidney transplants at our center: 2,596 (94.5%) in recipients 18
      to 64 years old and 150 (5.5%) in recipients 65 years or older. In our
      retrospective analysis, we determined outcomes such as patient and graft survival
      rates. To determine whether or not older recipients had an improved health
      related quality of life, we used the national SF-36 (short form) questionnaire.
      We compared those results with a group of younger recipients and with national
      age-appropriate norms. RESULTS: The mean recipient age was 69.1 years in the
      older group vs. 42.8 years in the younger group (p < 0.001). Living donors were
      used in 43.3% of the transplants in the older group vs. 47.5% in the younger
      group (p < 0.01). At 5 years posttransplant, patient and graft survival rates
      were 73% and 68% in the older group vs. 86% and 79% in the younger group (p <
      0.001). We analyzed the SF-36 responses for all recipients with completed forms:
      42 completed forms from the older group vs. 149 from the younger group. The
      overall benefit to quality of life was similar for both groups. General physical
      health was rated slightly higher than national norms in both groups. Benefits to
      mental health were more pronounced in the older group. CONCLUSION: Kidney
      transplants can be performed in older recipients with acceptable outcomes. Such
      recipients enjoy significant benefits to their quality of life after a
      transplant, similar to benefits seen in younger recipients. Older age, by itself,
      should not be a contraindication to a transplant.

PMID- 15859912
TI  - Outcomes in 139 cases of biliary tract reconstructions from a transplant surgery
      center.
AB  - OBJECTIVES: The purpose of this study is to report our single institution
      transplant surgery referral center's experience with 139 consecutive biliary
      tract reconstructions performed in a mixed cohort of liver transplant recipients
      and patients with biliary tract malignancies, iatrogenic injuries, or other
      benign biliary pathology. MATERIALS AND METHODS: Between July 1999 and February
      2003, 139 biliary tract reconstructions were performed in 119 patients, using
      five various types of biliary reconstructions. The records and operative notes of
      all patients were reviewed with particular attention to surgical technique,
      operative mortality, post-operative complications and post-operative liver
      function tests with respect to biliary function. RESULTS: The mean duration of
      follow-up was 19.4 months (range 1.0 - 44.7 months). We were pleased to find
      excellent results from bilio-enteric reconstruction as no patient in our series
      developed cholangitis, jaundice or liver failure. CONCLUSION: Our goal is to
      inform the hepatobiliary and general surgeons of the principles of restoring
      biliary drainage that have arisen from our experience in a variety of
      reconstruction.

PMID- 15859913
TI  - Induction of immunosuppression with polyclonal antithymocyte globulins: an
      overview.
AB  - The induction of immunological tolerance to solid organ allograft is currently a
      subject of major investigation due to the morbidity and mortality related to
      immunosuppressive therapy. Immunosuppression induction by recipient treatment may
      allow to tailoring the timing and dosage of standard therapy not only reducing
      adverse reactions but also improving the graft outcome. Depletion of recipient T
      cells with polyclonal antithymocyte globulins is one of the methods nowadays
      investigated both in experimental and clinical procedures, demonstrating a better
      outcome of organ engraftment. Our intention is to give an overview of the
      literature about the mechanisms of action of polyclonal ATGs, the status of
      induction treatment in clinical and experimental transplantation as well as of
      the possible pathophysiological relationships with acquired tolerance, delayed
      graft failure and ischemia-reperfusion injury.

PMID- 15859914
TI  - Effect of brain death and non-heart-beating kidney donation on renal function and
      injury: an assessment in the isolated perfused rat kidney.
AB  - OBJECTIVES: Ischemic injury to the renal allograft prior to implantation is
      considered as the major cause of primary non and never-function (PNF) and delayed
      graft function (DGF). Evidence has been put forward that brain dead and non-heart
      beating (NHB) donor organs are of marginal quality compared to living donors. The
      purpose of this study was to evaluate renal function and injury of brain dead and
      NHB donor kidneys using the isolated perfused rat kidney. MATERIAL AND METHODS:
      Fisher F344 rats were either maintained brain death for 4 hr or subjected to
      cardiac arrest for 45 min (NHB). Living rats served as controls. To omit
      additional effects of cold ischemia, kidneys were immediately reperfused. Renal
      function and injury were assessed by monitoring urine production, glomerular
      filtration rate (GFR), Na+ and K+ reabsorption, glucose metabolism and
      reabsorption, as well as release of brush border, lysosomal, and intracellular
      enzymes. RESULTS: Renal dysfunction and injury were most pronounced in NHB donor
      kidneys reflected by a highly reduced urine production, anaerobic glucose
      metabolism resulting in lactate formation, and significant higher luminal release
      of intracellular and lysosomal enzymes. Brain dead kidneys showed an increased
      urine production and were functionally abnormal in K+ reabsorption showing a net
      excretion of K+, probably as a result of ATP depletion. Loss of brush border
      occurred during brain death and cardiac arrest. CONCLUSIONS: Both, brain death
      and cardiac arrest have deleterious effects on renal function and renal injury.
      The ischemically injured NHB donor kidney was functionally inferior compared to
      the brain dead donor kidney and living donor kidneys. However, both brain dead
      and NHB kidneys showed considerable renal damage compared to kidneys from living
      donors.

PMID- 15859915
TI  - important social factors that affect organ transplantation in Islamic countries.
AB  - Social attitudes and beliefs have direct and strong impact on people's acceptance
      of organ donation and brain death, and therefore affect the entire practice of
      organ transplantation. The views differ from one society to another, and they at
      least partially explain regional variations in the world with respect to success
      of organ transplantation. Social attitudes and ethics in Islamic countries are
      closely intertwined with Islamic tradition, teachings and heritage. These
      positions are strongly adhered to in many Islamic countries, and by Moslems who
      live in countries that are not predominantly Islamic. We feel that transplant
      physicians and transplant coordinators should be aware of these factors when
      dealing with potential donors and recipients. Decision-making can be facilitated
      if these issues are considered prior to consulting with a donor's family and if
      an appropriate compassionate explanation of need for transplantation and basis of
      brain death diagnosis is provided based on a knowledge of underlying social
      constraints. Such steps can make the donation process smoother for both health
      care workers and the family.

PMID- 15859916
TI  - Progress in tissue engineering and organogenesis in transplantation medicine.
AB  - Tissue engineering is an attempt to culture living tissues for surgical
      transplantation. In vitro and in vivo approaches have produced vascular and
      cardiovascular components, bone, cartilage, gastro-intestinal organs, and liver.
      Organogenesis is a different approach to create new organs for transplantation
      from embryonic tissue implanted into the omentum of the recipient. This technique
      has been employed in creating kidney and pancreas in animals. Tissue engineering
      and organogenesis are the future of transplantation medicine. The progress in
      this field is of tremendous importance because it can produce a new generation of
      morphologically complex tissues and organs. In this review article we have
      summarized the most relevant experiences in this area, including its perspectives
      for therapeutical applications.

PMID- 15859917
TI  - ABO incompatible kidney transplantation --immunological aspect-.
AB  - ABO incompatible kidney transplantation (ABOINCKT) has been developed in Japan
      because of the shortage of cadaveric donors. We have performed 76 living-donor
      ABOINCKT in our center. Donor blood type antibody was removed by immunoadsorption
      or plasmapheresis and exchange. Immunosuppression consisted of cyclosporine or
      tacrolimus, steroid, and cyclophosphamide or azathioprine or mycophenolate
      mofetil and, recently, basiliximab. Splenectomy was routinely performed during
      the transplantation surgery. Donor blood type antigen was strongly expressed on
      the vascular endothelium at all time points and in all conditions
      posttransplantation. Red blood cell agglutination reaction (RBAR) was positive
      only in renal tissues from a patient with delayed hyperacute rejection. Donor
      specific antibody suppression was observed in 18 ABOINCKT recipients with blood
      type O from a donor with blood type A1 or B. ADCC activity was detected after pre
      treatment. Acute humoral rejection in ABOINCKT can result from ADCC, as well as
      by antigen-antibody reaction. Five year graft and patient survival rates were 75%
      and 64% in 37 ABOINCKT recipients from June 1989 through December 1996, however
      they have been 100% in 39 ABOINCKT recipients since January 1997. Accommodation
      has been produced in ABOINCKT with the co-existence of blood type antigen and
      antibody. Currently, ABOINCKT is an alternative which should be considered,
      particularly for blood type O patients with extended waits for cadaveric
      transplantation and for pediatric patients.

PMID- 15859918
TI  - Bioavailability versus bioequivalence: the cyclosporine model.
AB  - The quest for a fixed-dose immunosuppressive drug continues. Experience with
      cyclosporine, tacrolimus and mycophenolate mofetil has taught us that there is no
      correlation between dose and clinical events. These data indicate that the
      concentration of the drug at the site of action (bioavailability) of each of
      these agents differs from one patient to the next. In addition, the
      bioequivalence (concentration of intact drug at the site of action resulting in a
      measurable response [effect]) may differ among individuals. Technically, it is
      very difficult to measure the drug concentration at a particular site, especially
      in organs or tissues that are not directly accessible. Therapeutic drug-blood
      level monitoring is a simple indirect method that is used to estimate both
      bioavailability and bioequivalence. However, the immunosuppressive effect of all
      these drugs is initiated by binding to receptors on the surface of lymphocytes,
      which leads to inhibition of cytokine production and proliferation of activated
      lymphocytes. Thus, it would be more advantageous to monitor the level and effect
      of these drugs at the site of action (bioequivalence), the lymphocyte. This
      report describes an assay of this type that was developed for monitoring
      transplant patients at one center. The assay is based on measuring drug levels in
      the cytoplasm of lymphocytes. It is quick and easy to perform (20 samples per
      hour), inexpensive, and reproducible. The between-run Coefficient of Variance
      (CV) is 5.4 and a within-run CV is 3.1. For this study, blood and lymphocyte drug
      levels in transplant patients were determined and correlated with graft function
      and clinical events (biopsy-proven rejection and/ or toxicity).

PMID- 15859919
TI  - Ethical issues in organ and tissue transplantation.
AB  - Clinical organ transplantation provides a way of giving the gift of life to
      patients with terminal failure of vital organs, which requires the participation
      of other fellow human beings and of society by donating organs from deceased or
      living individuals. The increasing incidence of vital organ failure and the
      inadequate supply of organs, especially from cadavers, has created a wide gap
      between organ supply and organ demand, which has resulted in very long waiting
      times to receive an organ as well as an increasing number of deaths while
      waiting. These events have raised many ethical, moral and societal issues
      regarding supply, the methods of organ allocation the use of living donors as
      volunteers including minors. It has also led to the practice of organ sale by
      entrepreneurs for financial gains in some parts the world through exploitation of
      the poor, for the benefit of the wealthy. The current advances in immunology and
      tissue engineering and the use of animal organs, xenotransplantation, while
      offering very promising solutions to many of these problems, also raise
      additional ethical and medical issues, which must be considered by the medical
      profession as well as society. This review deals with the ethical and moral
      issues generated by the current advances in organ transplantation, the problem of
      organ supply versus organ demand and the appropriate allocation of available
      organs. It deals with the risks and benefits of organ donation from living
      donors, the appropriate and acceptable methods to increase organ donation from
      the deceased through the adoption of the principle of 'presumed consent', the
      right methods of providing acceptable appreciation and compensation for the
      family of the deceased as well as volunteer and altruistic donors, and the duties
      and responsibilities of the medical profession and society to help fellow humans.
      The review also deals with the appropriate and ethically acceptable ways of
      utilizing the recent advances of stem cell transplantation from adult versus
      fetal donors, tissue engineering and the use of organs from animals or
      xenotransplantation. It is emphasized that clinical organ and tissue
      transplantation can be more beneficial and life saving if everyone involved in
      the process, including physicians and medical institutions, respect and consider
      the best interests of the patients, as well as honor the ethical, moral and
      religious values of society.

PMID- 15859920
TI  - The science of stem cells: ethical, legal and social issues.
AB  - Stem cells are exciting to physicians, scientists and patients because of their
      potential to develop into many different cell types, tissues and perhaps even
      organs that can possibly be used to treat large numbers of patients with a
      variety of diseases. Scientific research, while it is still at a very early
      stage, is developing rapidly and creating enormous challenges for ethicists and
      policy-makers, especially in relation to embryonic stem cells. An understanding
      of the scientific facts of stem cell science and technology per se, the
      embryology and the associated terminology is critically important to making
      ethically sound policy judgments. The facts, definitions and terminology are
      confusing and are liable to misuse by those who seek to further a particular
      position. In this paper we provide a concise overview of the important scientific
      facts related to embryology and embryonic stem cells and highlight some recent
      scientific developments that are salient for the purpose of understanding the
      ethical, legal and social issues that have arisen and will continue to arise and
      be debated.

PMID- 15859921
TI  - Outcome of mucormycosis in liver transplantation: four cases and a review of
      literature.
AB  - Mucormycosis is a rare but highly invasive fungal infection that occurs in
      transplant recipients. The literature contains descriptions of 12 cases of
      mucormycosis after orthotopic liver transplantation (OLT). This report describes
      the fatal courses in four patients at our center who developed mucormycosis after
      liver transplantation. Of 51 liver transplant recipients who received grafts
      between December 1993 and April 2003, 4 (7.8%; 3 males and 1 female) developed
      mucormycosis. The primary liver diseases in the four cases were Wilson's disease,
      autoimmune hepatitis, primary biliary cirrhosis, and cryptogenic cirrhosis. Three
      of the transplants were harvested by another team and shipped to our center. We
      concluded that selection of poor transplant candidates, prolonged antibiotic
      therapy and/or hospitalization prior to OLT, and breaks in aseptic technique
      during harvesting, shipping, and during operation are the main reasons for the
      high incidence of mucormycosis in our OLT patients.

PMID- 15859922
TI  - The beginning of clinical tolerance in solid organ allografts.
AB  - Development of effective multidrug immunosuppressive regimens and improvements in
      the management of chronically immunosuppressed patients have produced
      extraordinary patient and allograft survival in clinical organ transplantation.
      Unfortunately, significant problems of morbidity and mortality related to chronic
      immunosuppression remain. Thus, there is an enormous motivation and interest in
      inducing specific unresponsiveness (tolerance) to clinical solid organ
      allografts. Operational clinical tolerance may be defined as stable, normal graft
      function in the total absence of a requirement for maintenance immunosuppression.
      Alternatively, the concept of employing tolerogenic strategies to permit graft
      acceptance with dramatically reduced immunosuppression requirements is referred
      to as prope' or minimal immunosuppression tolerance. There have been isolated
      examples of clinical tolerance, usually in the context of spontaneous or induced
      donor chimerism, excellent HLA matching, and/or drug weaning or patient
      noncompliance. The various attempts that are currently being employed to induce
      some type of clinical tolerance are reviewed in this manuscript. Strategies in
      which all immunosuppression was to be withdrawn from the recipient (donor
      specific unresponsiveness) are first discussed. These include strategies that
      utilize initial immunoablation with varying doses of irradiation and/or
      lymphocytic antibodies with or without donor-specific bone marrow infusion and
      short-term standard immunosuppressive therapy. Strategies to induce prope' or
      minimal immunosuppression tolerance that utilize induction lymphoablation with
      polyclonal or monoclonal antilymphocyte antibodies, with or without donor bone
      marrow infusion, followed by limited low-dose immunosuppressive therapy are also
      discussed. The ethical considerations in testing clinical tolerance strategies
      and protocols are discussed in detail. The limited number of clinical tolerance
      studies already available affirms that carefully supervised weaning of
      immunosuppressive drugs in controlled tolerance trials is not unreasonable,
      especially when monitored by protocol allograft biopsies. Initial results suggest
      that aggressively treated low-grade steroid-responsive rejection reactions in the
      absence of immune-mediated tissue destruction does not necessarily require
      resumption of high-dose immunosuppression. Finally, the role of donor bone marrow
      infusions in facilitating tolerance/hyporesponsiveness induction needs to be
      studied and expanded.

PMID- 15859923
TI  - Basic and clinical research in polyomavirus nephropathy.
AB  - Over the last decade, polyomavirus nephropathy (PVN) has emerged as an important
      cause of renal allograft dysfunction and graft loss. PVN occurs with a prevalence
      of 1%-8% in renal transplant recipients and is most commonly reported within the
      first 12 months posttransplant. The human polyomavirus, BK virus, is thought to
      be the primary etiologic agent of PVN. Risk factors for PVN are not well defined
      and are most likely a result of a complex interaction between multiple donor and
      recipient factors. Definitive diagnosis of PVN is made through histological
      assessment of a renal allograft biopsy. Recent studies have also evaluated
      noninvasive urine and serum markers for screening of BK virus replication and as
      adjunct tools in PVN diagnosis and monitoring. The principal treatment for PVN is
      immunosuppression reduction, but this must be balanced against the risks of
      rejection. If rejection occurs concurrently with PVN, a brief increase in
      immunosuppression to treat the rejection episode followed by a subsequent
      reduction in immunosuppression is recommended. No antiviral treatments for PVN
      have been approved by the Food and Drug Administration. Although the antiviral
      drug cidofovir has shown in vitro activity against murine polyomaviruses, and has
      been effective in some patients, it is associated with significant
      nephrotoxicity. Small series of patients treated with leflunomide and intravenous
      immune globulin therapy for PVN have also recently been reported.
      Retransplantation after graft loss due to PVN is feasible, but experience is
      limited. Current research is focusing on identifying PVN risk factors, refining
      screening, diagnostic and monitoring methods, and developing therapy for
      prophylaxis and treatment of PVN with the goals of decreasing the prevalence of
      PVN and improving allograft outcomes in renal transplant recipients diagnosed
      with PVN. This review will present recent advances in basic and clinical research
      related to PVN and renal transplantation.

PMID- 15859924
TI  - Molecular signaling pathways in ischemia/reperfusion.
AB  - Ischemia and reperfusion (I/R) is an important pathologic phenomenon that has not
      been completely defined from the perspective of the molecular signaling pathways
      developed immediately at its inception to minutes and hours thereafter. From the
      practical point of view, we have divided I/R into 3 phases: phase I, which occurs
      seconds to minutes after the injury and is associated with changes dependent on
      the activation of phospholipases, intracellular calcium, eicosanoids, other lipid
      molecules, protein kinases, inducible nitric oxide synthase, and the expression
      of preformed adhesion molecules like P-selectin; phase II, which occurs minutes
      to hours after I/R injury and is associated with the active transcription of
      protein synthesis of molecules like inflammatory cytokines (mainly tumor necrosis
      factor-alpha and interleukin 1) starting their signaling downstream from the
      membrane into the cytoplasm where kinases will be activated and send signals to
      the nucleus for the activation of transcription factors and further continuing
      with the inflammatory event; and phase III, which occurs several hours to days
      after I/R and is associated with the appearance of molecular chronic mechanisms
      of protection like the presence of anti-inflammatory cytokines of the IL-10 type,
      late adhesion molecules, and other growth factors such as TGF-beta. This
      completes the whole molecular event related to I/R injury.

PMID- 15859925
TI  - Liver transplantation for biliary atresia: 19-year, single-center experience.
AB  - OBJECTIVES: In this study, we describe our 19-year experience with liver
      transplantation as the definitive treatment for congenital biliary atresia.
      MATERIALS AND METHODS: We performed a retrospective study of 115 liver
      transplants from 1984 to 2003 in 85 patients with congenital biliary atresia. We
      determined the impact of era of transplantation (1984-1993 and 1994-2003),
      recipient age (< 1 and > 1), prior portoenterostomy, and type of surgery (whole-,
      reduced-, and split-liver transplant) on the outcome of the transplant. RESULTS:
      Overall long-term survival is 83%. Survival is greater in the more-recent era. No
      impact of age or prior portoenterostomy on survival was seen. Split-liver grafts
      showed superior graft survival, whereas reduced-liver transplants had the worst
      overall graft survival. CONCLUSIONS: Our results confirm that long-term patient
      survival after liver transplantation for congenital biliary atresia is excellent.
      When required, partial liver grafts provide excellent long-term outcome.

PMID- 15859926
TI  - Analysis of marginal donor parameters in liver transplantation for primary
      biliary cirrhosis.
AB  - The shortage in cadaveric donor livers is pushing the transplant centers to
      expand the pool by using "marginal" donors. Primary biliary cirrhosis (PBC)
      remains an important indication for transplantation. We conducted a retrospective
      analysis of prospectively collected data in a well-defined group of patients with
      PBC where 301 consecutive donor-PBC recipient pairs transplanted were analyzed to
      identify donor and operative factors influencing recipient outcome. Mean follow
      up was 56 months. The 1-, 3- and 5-year actuarial patient and graft survival was
      93.97%, 90.64%, and 81.75%, and 85.49%, 82.57%, and 75.21%, respectively. Factors
      showing influence in decreased total patient survival were recipient old age (P =
      0.003) and low recipient albumin (P = 0.01). However, the only variables showing
      an association with decreased patient survival within 90 days are old donor age
      (P = 0.002) and high donor body weight (P = 0.03) or high body mass index (BMI)
      (P = 0.055). Cold ischaemic time (CIT) of 18 hours showed statistical
      significance in patient survival (P = 0.025). Obesity did have a significant
      adverse impact on survival compared with normal or overweight donors (BMI < 30),
      decreasing survival by 50% at 5 years. In conclusion, this study of several
      factors considered "marginal" for transplantation in a recipient population with
      predictable liver disease (PBC), donor BMI and age were shown to be associated
      with decreased graft and patient survival.

PMID- 15859927
TI  - Reconstruction of the hepatic venous outflow in piggyback liver transplantation.
AB  - OBJECTIVES: The "piggyback" hepatic vein reconstruction and orthotopic liver
      transplantation (PBOLT) is a technique of liver transplantation that leaves the
      recipient inferior vena cava (IVC) intact, often avoiding the use of venovenous
      bypass (VVBP). Our study investigated whether patient morbidity and mortality
      after PB-OLT was comparable to that of the standard technique of orthotopic liver
      transplant (STD-OLT), which generally requires VVBP. MATERIALS AND METHODS: We
      reviewed 220 consecutive adult OLTs performed at a single institution. In the PB
      OLT technique, the IVC was left intact. The suprahepatic IVC was anastomosed to a
      cuff, fashioned from the confluence of the recipient left and middle hepatic
      veins. The donor infrahepatic IVC was oversewn. The STD-OLT technique was used
      when patient conditions precluded PB-OLT. VVBP was required in 83% of STD-OLT
      cases and no cases of PB-OLT. RESULTS: PB-OLT was successfully performed in 122
      of the 220 patients (55.5%), and STD-OLT was performed in 98 patients (44.5%).
      The 1- and 3-year survival rates, 96.3% and 87.8% vs 96.7% and 84.0% for PB-OLT
      and STD-OLTs, respectively, did not differ significantly. Total ischemic time and
      length of posttransplant hospital stay were shorter in the PB-OLT group. The
      total operative time and red cell transfusion requirements were comparable. The
      rate of suprahepatic IVC-related complications did not differ between the two
      groups, and no VVBPrelated complications were seen. CONCLUSIONS: The PB-OLT can
      be used to avoid VVBP and its attendant risks in the majority of patients
      undergoing OLT. In the current era of transplantation, the PB-OLT should be
      considered a safe technique for OLT.

PMID- 15859928
TI  - Qualitative detection of human cytomegalovirus DNA in the plasma of bone marrow
      transplant recipients: value as a predictor of disease progression.
AB  - OBJECTIVE: The aim of this prospective study was to determine whether human
      cytomegalovirus (HCMV)-DNA detected by polymerase chain reaction (PCR) analysis
      in the plasma of bone marrow transplant (BMT) patients is a predictor of HCMV
      disease progression. METHODS: Plasma samples were collected from 15 patients who
      received allogenic BMTs. Each individual was sampled 1 week before and then
      weekly for 17 weeks after transplantation. The 270 plasma specimens were
      processed with a PCR method for detecting HCMV-DNA. Patients were also physically
      examined for signs or symptoms of HCMV-related disease. RESULTS: Eight (53.5%) of
      the 15 patients tested positive for HCMV-DNA. Two (25%) of these 8 individuals
      also had positive PCR findings before transplantation. Six (75%) of the 8 HCMV
      DNA-positive patients had positive plasma-PCR results a week before clinical
      symptoms developed. The other 2 (25%) remained asymptomatic throughout their
      hospital stay. All 6 symptomatic cases were treated with ganciclovir, and 4
      converted to negative plasma-PCR status at a median of 21 days. There was a
      significant correlation between PCR-detection of HCMVDNA in plasma and presence
      of HCMV-related symptoms (P < 0.01). CONCLUSION: Qualitative plasma-PCR analysis
      before and after bone marrow transplantation is a valuable way to screen for HCMV
      infection in BMT patients. Plasma-PCR monitoring of HCMV activity in this patient
      group might make it possible to administer an antiviral drug and thus reduce
      mortality. However, quantitative PCR is still considered the best way to
      accurately identify active HCMV infection and monitor treatment.

PMID- 15859929
TI  - Ten-year follow-up of recipients of a kidney or heart transplant who received
      induction therapy with a monoclonal antibody against the interleukin-2 receptor.
AB  - OBJECTIVES: Twelve years ago, we performed two randomized clinical trials to
      investigate safety and efficacy of induction therapy with BT563, a highly potent
      murine monoclonal antibody against the interleukin-2 receptor after kidney and
      heart transplantation. We analyzed the long-term safety and efficacy data from
      all 120 patients who participated in the two randomized trials after kidney and
      heart transplantation 10 years ago. MATERIALS AND METHODS: One of these two
      trials was a randomized, double-blind, placebo-controlled trial, with 60 primary
      and secondary kidney allograft recipients (cadaveric and living-related donors).
      The control group was treated with the standard regimen at that time, consisting
      of cyclosporin and prednisone. In the study group, BT563 was added for 10 days.
      The second trial was a randomized, double-blind trial, with 60 recipients of a
      primary heart transplant. In that study, we compared induction therapy with BT563
      with the standard regimen at that time, consisting of cyclosporin, prednisone,
      and OKT3 (both induction agents were given for 7 days). RESULTS: Patient survival
      in the kidney trial was excellent: in the BT563 group, 24 patients were alive
      (80%), and in the placebo, group 21 (70%) 10 years after transplantation. Also,
      graft survival was good: in the BT563 group, 63.3% of the kidneys (19/30) were
      functioning, in the placebo group, 72.4% (21/29) were functioning (P = 0.455).
      Also, in the heart study, patient (and graft) survival was excellent: 18 patients
      were alive in the BT563 group (58%), and in the OKT3 group, 21 (72%) patients
      were alive (P = ns). No increase in the incidence of malignancies was observed
      between patients treated with BT563 compared with the control groups. Patients
      following heart transplantation more often suffered from a malignancy than did
      patients after kidney transplantation (20/60 vs 10/59). CONCLUSIONS: We report
      follow-up data on all patients participating in the two randomized trials, and
      our data reflect a total of 932 years of patient follow-up. Patient and graft
      survival appear to be excellent in both the BT563-treated patients and the
      control groups. BT563 treatment was not associated with an increased likelihood
      of developing infections or malignancies.

PMID- 15859930
TI  - Lessons learned from ABO-incompatible living donor kidney transplantation: 20
      years later.
AB  - From June 1982 to November 1989, 39 ABO-incompatible living kidney transplants
      were performed in 38 recipients. Pretransplant therapies included platelets donor
      transfusion (21/39), 2 to 5 plasmapheresis sessions (39/39), cyclosporin A with
      or without azathioprine (33/39) along with polyclonal Abs (36/39) and splenectomy
      at the time of transplantation (37/39). The last patient who received 2 ABO
      incompatible transplants was previously splenectomized (end-stage renal failure
      due to a cortical necrosis following a traumatic spleen rupture). Three other
      patients who did not undergo a splenectomy at the time of transplantation were
      not included in that series but hyperacutely rejected their transplants during
      the first postoperative week. The 31 ABO-incompatible living related donor graft
      recipients are alive. Graft loss occurred from acute and/or hyperacute rejection
      in 5 cases (none below 15 years of age) and from chronic rejection in 8 cases. By
      contrast, among the 8 ABO-incompatible living unrelated donor graft recipients,
      only one renal graft is still functioning 20 years later. Graft survival rates
      are better in the group of patients < 15 years (100%, 89%, 78%, and 78% at 2, 5,
      10, and 15 years respectively) compared with the group > 15 years (77%, 77%, 64%,
      and 59% respectively; NS). Today, 20 years later, prospective randomized studies
      testing different steps in the preparation protocol are still lacking.
      Plasmaphereses were replaced by double filtration plasmapheresis and
      immunoadsorption. Splenectomy seems to be a prerequisite for successful ABO
      incompatible living kidney transplantation but IV Ig globulins and rituximab are
      currently being successfully used without splenectomy along with the new
      immunosuppressive drugs. As the procedure remains unchanged, it might be reserved
      to patients where cadaver graft could not be a valuable alternative, especially
      for recipients < 15 years of age with a living related ABO-incompatible donor.

PMID- 15859931
TI  - Middle East Society for Organ Transplantation (MESOT) Transplant Registry.
AB  - During the seventies, sporadic renal transplants were performed in few MESOT
      region countries, mainly Turkey, Iran, Egypt, and Lebanon. Since the introduction
      of cyclosporine in the early eighties, transplantation has become the preferred
      therapeutic modality for end-stage renal failure. In 1986, the Islamic
      theologians (Al Aloma) issued what became known as the Amman declaration, in
      which they accepted brain death and retrieval and transplantation of organs from
      living and cadaveric donors. Based on this and similar declarations, all Middle
      Eastern countries except Egypt passed laws that allow cadaveric transplantation
      and regulate live donations. Iran, Turkey, Saudi Arabia, Kuwait, Tunisia, Jordan,
      and Lebanon all have current active cadaveric programs and perform liver, heart,
      pancreas, and lung transplants. More than 5088 renal transplants/year are
      performed in the region with Iran leading with 1600. The cumulative number of
      renal transplant patients is now nearly 60,000. With a 2003 population of
      600,682,175, the rate/million for renal transplantation in the MESOT region is a
      mere 9/million. Rates of renal transplantation range from 31/million in some
      countries to 0 in others. The major obstacle in establishing an accurate number
      of transplants is "tourist transplantation," in which the same transplanted
      patients are registered in different countries. Although cadaveric programs have
      been active for more than 10 years, live-related and nonrelated transplants
      account for nearly 85% of the total transplants. The data presented were
      collected from MESOT representatives in the region and from publications. For
      proper compilation of the registry, a format is being proposed that will be
      presented at the Congress for review and adaptation. Even with the limited
      resources in the region, immunosuppressive drugs for induction and maintenance
      therapy are available and are used. Costs for transplantation and
      immunosuppressive therapy are either totally or heavily supported by governmental
      agencies.

PMID- 15859932
TI  - Governed financial incentives as an alternative to altruistic organ donation.
AB  - In 1984, an offensive proposal for kidney sales by a US physician led the
      National Organ Transplant Act to become a law in the United States. Similar
      legislation passed in many other countries. An ethical consensus developed around
      the world that there should be no monetary compensation for transplantable
      organs, either from living or deceased persons. Unfortunately, the altruistic
      supply of organs has been much less than adequate, and thousands of patients die
      each year waiting for organ transplantation. As the altruistic system of organ
      donation has met with failure, some from the transplant community believe that
      altruism alone is not enough to satisfy the needs of the thousands of patients on
      organ transplant waiting lists, and providing some financial incentives or social
      benefits to organ sources is necessary to increase the number of cadaveric or
      living organ donations. In this article, the many controversies surrounding
      altruistic and compensated organ donation systems are discussed. The Iran model
      for renal transplantation, a compensated and well-regulated living-unrelated
      donor renal transplantation program that has successfully eliminated a renal
      transplant waiting list in Iran, is briefly reviewed.

PMID- 15859933
TI  - Ageing and immunosuppression in kidney transplantation.
AB  - Modern approaches to tailor-made, individualized immunosuppressive therapy for
      patients receiving organ transplantation require a rethinking of therapeutic
      strategies when it comes to older persons receiving kidney transplants,
      especially from deceased older donors. This review article makes the case for the
      use of calcineurin-inhibitor-free immunosuppressive induction/maintenance
      protocols in this "worst-case scenario" and discusses the theoretical and
      clinical data that support this recommendation. We will discuss modern theories
      of ageing, emphasizing the free-radical theory in relation to new insights into
      the mechanisms of innate immunity. In this context, a new, modified theory of
      ageing is presented. Increased generation of reactive oxygen species during
      ageing, via increased leakage of these oxidizing molecules from mitochondria, may
      contribute to senescence and age-related diseases by direct damage to
      intracellular DNA, proteins, and lipids. In addition, free-radical-mediated
      tissue injury, accompanied by induction of damage-associated molecular patterns,
      may result in activation of both inflammatory and vascular cells of the innate
      immune system, contributing (via inflammatory processes) to ageing and age
      related diseases such as atherosclerosis. Calcineurin-inhibiting agents have been
      shown to induce oxidative stress and are thus defined as "proageing" drugs. Their
      use in older patients may aggravate the preexisting oxidized intracellular state
      and therefore should be avoided. In contrast, inosine-monophosphate dehydrogenase
      inhibiting agents such as mycophenolate mofetil have been shown to even
      ameliorate oxidative stress and are thus defined as "antiageing" drugs.
      Therefore, their use for immunosuppression in older patients receiving kidney
      transplantation is suggested. This recommendation is supported by data from a
      prospective trial on the application of a calcineurin inhibitor-free,
      mycophenolate-mofetil--based induction/ maintenance immunosuppressive protocol in
      older recipients of kidneys from deceased older donors: the 5-year patient and 5
      year allograft survival rates are currently 87% and 70%, respectively.

PMID- 15859934
TI  - Kidney transplantation in a veterans administration medical center: 40 years'
      experience.
AB  - OBJECTIVES: Advances in immunosuppressive therapy have led to substantial
      improvements in kidney transplant outcomes in the past 20 years. Kidney
      transplantation activity started in 1963 at the Veterans Administration Medical
      Center in Nashville, Tennessee, and continues to grow with increasing numbers of
      transplants from living-related and unrelated donors. In this study, patient and
      graft survival rates during 2 different periods were evaluated and compared with
      non-veterans-administration centers. MATERIALS AND METHODS: Six hundred fourteen
      kidney transplants were performed between March 1963 and December 2002. For
      analytic purposes, the 40-year experience was divided into 2 eras based on the
      immunosuppressive agents used. Azathioprine and prednisone were the
      immunosuppressive agents used in era 1. A calcineurin-inhibitor-based triple
      immunosuppressive regimen initially including azathioprine and prednisone and
      later, mycophenolate mofetil and prednisone, was the preferred immunosuppressive
      regimen in era 2. RESULTS: In era 1, 1-year patient and graft survival rates were
      72.5% and 50%, and 89% and 75% for deceased-donor and living-donor transplants
      respectively. In era 2, patient survival rates increased to 95.1% and 87.8% for 1
      and 3 years respectively, while graft survival increased to 87.6% and 74.9%.
      Forty-three percent of deceased-donor and 21% of living-donor kidneys were lost
      owing to rejection in era 1. In era 2, the incidence of acute rejection was 14.5%
      overall. CONCLUSIONS: Overall, our results are comparable with non-veterans
      administration centers and the national average and show that kidney
      transplantation offers veteran patients with end-stage renal disease a safe and
      effective treatment with increased quality of life.

PMID- 15859935
TI  - Impact of hepatitis C virus infection on short-term outcomes in renal
      transplantation.
AB  - Hepatitis C virus is an RNA virus with 6 known genotypes. Prevalence of hepatitis
      C virus infection in the world is almost 3%. In patients undergoing hemodialysis,
      prevalence of hepatitis C virus positivity is reported to be from 1%-54%
      depending on the methods used for detection. Liver disease in kidney transplant
      recipients has been attributed to hepatitis B virus, hepatitis C virus, Epstein
      Barr virus, cytomegalovirus, ethanol, hemosiderosis, and drugs such as
      azathioprine and cyclosporine A. Hepatitis C virus infection is currently the
      main cause of chronic liver disease in this group, and it may affect allograft
      outcome. Whether hepatitis C virus infection after renal transplantation
      adversely affects graft and patient survival remains controversial. Several
      series have reported no impact on short- and long-term patient and graft
      survival. In fact, comparative studies using different immunosuppressive
      protocols are not available. The differences in the results of these studies may
      be explained by confounding factors, for example, differences in
      immunosuppressive protocols, study design, methodology of diagnosing hepatitis C
      virus infection, and differences in hepatitis C virus genotypes. Treatment
      protocols for hepatitis-C-virus--associated liver disease should be considered
      before renal transplantation. Nevertheless, transplantation is the best option
      for patients with hepatitis C virus with end-stage renal disease, and less
      hepatotoxic immunosuppressive agents may decrease the incidence of posttransplant
      liver disease in patients with hepatitis C virus. This review will discuss the
      studies with specific emphasis on the impact of hepatitis C virus infection on
      short-term outcome in renal transplantation.

PMID- 15859936
TI  - Back table procedure for the modified piggyback technique of liver
      transplantation: a simple test to identify caval leaks on the bench.
AB  - OBJECTIVES: In October 2001, we elected to change from the standard orthotopic
      liver transplantation procedure to the modified piggyback technique with side-to
      side cavo-cavostomy, and to document complications such as caval leaks
      prospectively. Failure to identify and ligate caval tributaries during bench
      preparation of liver allografts results in troublesome hemorrhage after
      reperfusion. After our experience with the first 30 piggybacks, we introduced a
      simple leak test to resolve this problem. MATERIALS AND METHODS: The leak test
      consists of inflating the inferior vena cava with preservation solution via the
      infrahepatic inferior vena cava after closure of the suprahepatic inferior vena
      cava at the end of the bench procedure. Between October 2001 and July 2002, 112
      whole liver transplants were performed in 108 adults. Standard orthotopic liver
      transplantation (group 1) was performed in 25, modified piggyback without leak
      test (group 2) was performed in 30, and modified piggyback after leak test (group
      3) was performed in 57 patients. The incidence of caval leaks before and after
      introduction of the test was compared using the chi-square test. RESULTS: Nine
      patients in group 1 (36%) and 13 in group 2 (43%) required additional sutures to
      control bleeding from caval branches after reperfusion. In group 3, the leak test
      identified caval tributaries that required ligation in 20 livers (35%) before
      implantation; none bled after reperfusion. Of the 37 cases with negative leak
      test results, 3 (8%) subsequently bled from missed caval branches. Sensitivity,
      specificity, and accuracy for the leak test were 100%, 92.1%, and 94.7%
      respectively. CONCLUSIONS: Nearly all small branches of the inferior vena cava
      can be successfully identified during the back table procedure by performing a
      leak test.

PMID- 15859937
TI  - Laparoscopic donor nephrectomy--an Iranian model for developing countries: a cost
      effective no-rush approach.
AB  - OBJECTIVES: This study aimed to evaluate donor and graft outcome in kidney
      transplantations from laparoscopic donor nephrectomies. MATERIALS AND METHODS:
      From June 2000 to June 2004, 341 laparoscopic donor nephrectomies were performed.
      Demographics and hospital records were reviewed. Mean ages of donors and
      recipients were 27.59+/-4.80 years (range, 20-56 years) and 35.36+/-14.85 years
      (range, 3-75 years). RESULTS: Nephrectomy was left sided in 96.2%. Mean follow-up
      was 13.32+/-35.98 months. Mean warm ischemia time was 8.17 minutes (range, 2.5-19
      minutes). Mean operative time was 260.34 minutes. Median serum creatinine levels
      (mg/dL) of the recipients were 1.30, 1.45, and 1.20 at day 7, and at 1 and 12
      months. One-year graft survival was 92.7%, 94.6%, and 92.6% in the laparoscopic
      donor nephrectomy groups with warm ischemia times of less than 6, 6-10, and more
      than 10 minutes (P=NS). Conversion to open surgery occurred in 2.1% of donors,
      and reoperation was performed in 3.8% of laparoscopic donor nephrectomies. Blood
      transfusion was required in 7.1% of donors. Ureteral complications were observed
      in 2.1% of recipients. Vascular control was performed using medium-large clips
      instead of endo GIA, and the kidney was extracted via a suprapubic approach using
      the hand instead of an ENDOCATCH bag; hence, $600 was saved in each nephrectomy.
      No vascular accident occurred from pedicular vessels. CONCLUSIONS: Laparoscopic
      donor nephrectomy can be performed with a less-expensive setup (to be expanded in
      developing countries) without jeopardizing results. Because warm ischemic time in
      our study did not affect graft outcome significantly, there appears to be no need
      to rush harvesting the kidney to achieve a better quality kidney. Vascular
      control using nonautomatic clips instead of more costly endo GIA and hand
      extraction of the kidney is safe, practical, and economical.

PMID- 15859938
TI  - Use of ETS-FLEX endoscopic linear vascular cutter in donor nephrectomy and
      transplantation surgery: a single institution's experience.
AB  - OBJECTIVES: We describe our experience with the use of ETS-FLEX endoscopic linear
      vascular cutter from January 2000 to October 2004 in live-donor nephrectomy and
      pancreatic bench work. MATERIALS AND METHODS: In live-donor nephrectomy, ETS-FLEX
      endoscopic linear vascular cutter (ELVC) is used for the stapling and division of
      renal vessels and ureter. When positioned on a vessel, the vascular cutter
      applies 3 staple lines proximally and 3 distally, and the vessel in between them
      is divided. In pancreatic graft bench work, ELVC is applied in 3 steps: the
      splenectomy, ligation of the mesenteric root, and the ligation of any
      peripancreatic lymphatic tissue or small vessels. RESULTS: From October 2000 to
      October 2004, we performed 80 living-donor nephrectomies in 56 men and 24 women
      (mean age, 39 years; range, 24-63 years). Thirty-one grafts were with multiple
      vessels. Mean warm ischemia time was 60+/-5 seconds. Mean operative time was 60+/
      10 minutes. In all cases, there was no need for further hemostasis after removal
      of the kidney. There were no operative complications. All grafts were
      successfully revascularized with 100% graft survival (range of follow-up, 1-48
      months). Patients' length of stay in hospital was 3+/-1 days. We have used the
      ETS-FLEX ELVC in 30 pancreatic graft preparations since January 2000. Mean time
      taken for the bench work preparation including Y-graft anastomosis was 45 +/- 10
      minutes. Following revascularization, there was excellent perfusion with minimal
      and easily controllable bleeding that did not require blood transfusion.
      CONCLUSIONS: We believe that our use of the laparoscopic instrument, ETS-FLEX
      ELVC, with a mini-incision technique in live-donor nephrectomy and pancreatic
      graft preparation makes these complex and time-consuming procedures simple and
      fast, minimizing the chances of postoperative complications and resulting in
      excellent patient and graft survival.

PMID- 15859939
TI  - Parasitic infections in organ transplantation.
AB  - More than 340 parasitic species infect more than 3 billion people worldwide with
      varying morbidity and mortality. The Tropics constitute the main reservoir of
      infection with the highest clinical impact, owing to favorable ecological
      factors. Acquisition of infection, clinical severity, and outcome of a parasitic
      disease depend on innate and acquired host immunity as well as the parasite's own
      immune response against the host when infection is established. Organ transplant
      recipients may acquire significant parasitic disease in 3 ways: transmission with
      the graft, de novo infection, or activation of dormant infection as a consequence
      of immunosuppression. Malaria, Trypanosoma, Toxoplasma, and Leishmania are the
      principal parasites that may be transmitted with bone marrow, kidney, or liver
      homografts, and microsporidia with xenotransplants. De novo infection with
      malaria and kala-azar may occur in immunocompromised travelers visiting in
      endemic areas, while immunocompromised natives are subject to superinfection with
      different strains of endemic parasites, reinfection with schistosomiasis, or
      rarely, with primary infections such as acanthamoeba. The list of parasites that
      may be reactivated in the immunocompromised host includes giardiasis,
      balantidiasis, strongyloidiasis, capillariasis, malaria, Chagas' disease, and
      kalaazar. The broad clinical syndromes of parasitic infection in transplant
      recipients include prolonged pyrexia, lower gastrointestinal symptoms,
      bronchopneumonia, and meningoencephalitis. Specific syndromes include the
      hematologic manifestations of malaria, myocarditis in Chagas' disease, acute
      renal failure in malaria and leishmaniasis, and the typical skin lesions of
      Chagas' and cutaneous leishmaniasis. Many antiparasitic drugs have the potential
      for gastrointestinal, hepatic, renal, and hematologic toxicity, and may interact
      with the metabolism of immunosuppressive agents. It is recommended that
      transplant clinicians have a high index of suspicion of parasitic infections as
      an important transmission threat, as well as a potential cause of significant
      posttransplant morbidity.

PMID- 15859940
TI  - Causes of acute thrombotic microangiopathy in patients receiving kidney
      transplantation.
AB  - OBJECTIVES: Thrombotic microangiopathy is a well-known problem in patients
      following renal transplantation. In postrenal transplantation, thrombotic
      microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to
      determine the causes of thrombotic microangiopathy in a population of renal
      transplantation recipients and discuss the literature. MATERIALS AND METHODS: We
      investigated the causes of thrombotic microangiopathy during a 1-year period,
      from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh,
      Saudi Arabia, by reviewing the slides of all transplant biopsies (n=25) performed
      during this interval. Pre- and posttransplant crossmatching was done when
      possible. RESULTS: Five cases of thrombotic microangiopathy were found. Three of
      these cases were from the 25 transplantations performed at King Fahad National
      Guard Hospital, while the other 2 transplantations had been performed abroad and
      were referred to us for follow-up. Three cases were related to cyclosporine, and
      1 case was secondary to both cyclosporine and tacrolimus. The fifth case had
      features of thrombotic microangiopathy related to an antiphospholipid syndrome in
      a patient with systemic lupus erythematosus. CONCLUSIONS: In the literature, the
      most-frequent cause of hemolytic uremic syndrome in patients following renal
      transplantation is recurrence of the hemolytic uremic syndrome. Other causes
      include drug-related (cyclosporine, tacrolimus) toxicity, procoagulant status,
      and antibody-mediated rejection. We found that the most-frequent cause of
      thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In
      the current study, the frequency of thrombotic microangiopathy was similar to the
      percentage reported in the literature (20%).

PMID- 15859941
TI  - Mutagenic and cytotoxic effects of immunosuppressive drugs on human lymphocyte
      cultures.
AB  - OBJECTIVES: Immunosuppressive drugs such as cyclosporine A, mycophenolate
      mofetil, tacrolimus, and the immunosuppressive agent sirolimus are used
      effectively to prevent immunologic rejection after solid-organ transplantation.
      The most serious complication among patients undergoing immunosuppressive therapy
      is the risk of developing cancer. The question is whether the drugs used have
      mutagenic properties and so contribute to increased cancer risk. MATERIALS AND
      METHODS: We evaluated the mutagenic and cytotoxic effects of the above-mentioned
      drugs in human lymphocyte cultures with special consideration given to clinically
      relevant blood-drug concentrations. Mutagenicity was tested by analyzing
      micronuclei using the well-established cytokinesis-block micronucleus assay with
      cytochalasin B. To evaluate cytotoxicity, the cytokinesis-block proliferation
      index was calculated. Concentrations used ranged from 0.1-2 mug/mL for
      cyclosporine A, 1-20 microg/mL for mycophenolate mofetil, 5-40 ng/mL for
      tacrolimus, and 2.5-50 ng/mL for sirolimus. We also estimated mutagenicity and
      cytotoxicity in the blood of kidney transplanted patients using the above
      mentioned techniques. RESULTS: Cultures supplemented with mycophenolate mofetil
      or tacrolimus showed higher amounts of micronuclei when compared with solvent
      controls in all concentrations tested. Addition of cyclosporine A to cultures
      also led to a rise in the number of micronuclei at concentrations of 0.2 mug/mL
      and 0.4 mug/mL. In contrast with the other immunosuppressive drugs, sirolimus
      induced only weak mutagenic activity in the micronuclei test at its highest
      concentration (50 ng/mL). Cytotoxic effects were seen only in
      mycophenolatemofetil-supplemented cultures at all concentrations tested (P<0.01).
      In comparison with healthy persons, those with kidney transplants under
      immunosuppression displayed a broad reduction in the cytokinesis-block
      proliferation index (P<0.001) and a significant increase in the frequency of
      micronuclei (P<0.001). CONCLUSIONS: Our results indicate that mycophenolate
      mofetil and tacrolimus display more mutagenic effects in vitro than do
      cyclosporine A or sirolimus, and that transplanted patients exhibit higher
      amounts of micronuclei and a noteworthy reduction in the cytokinesis-block
      proliferation index compared with healthy persons.

PMID- 15859942
TI  - Overexpression of OSBP-related protein 2 (ORP2) induces changes in cellular
      cholesterol metabolism and enhances endocytosis.
AB  - ORP2 [OSBP (oxysterol-binding protein)-related protein 2] belongs to the 12
      member mammalian ORP gene/protein family. We characterize in the present study
      the effects of inducible ORP2 overexpression on cellular cholesterol metabolism
      in HeLa cells and compare the results with those obtained for CHO cells (Chinese
      hamster ovary cells) that express ORP2 constitutively. In both cell systems, the
      prominent phenotype is enhancement of [14C]cholesterol efflux to all
      extracellular acceptors, which results in a reduction of cellular free
      cholesterol. No change was observed in the plasma membrane cholesterol content or
      distribution between raft and non-raft domains upon ORP2 expression. However,
      elevated HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase activity and LDL (low
      density lipoprotein) receptor expression, as well as enhanced transport of newly
      synthesized cholesterol to a cyclodextrin-accessible pool, suggest that the ORP2
      expression stimulates transport of cholesterol out of the endoplasmic reticulum.
      In contrast with ORP2/CHO cells, the inducible ORP2/HeLa cells do not show down
      regulation of cholesterol esterification, suggesting that this effect represents
      an adaptive response to long-term cholesterol depletion in the CHO cell model.
      Finally, we provide evidence that ORP2 binds PtdIns(3,4,5)P(3) and enhances
      endocytosis, phenomena that are probably interconnected. Our results suggest a
      function of ORP2 in both cholesterol trafficking and control of endocytic
      membrane transport.

PMID- 15859943
TI  - Increased uterine arterial pressure and contractility of perfused swine uterus
      after treatment with serum from pre-eclamptic women and endothelin-1.
AB  - The present study was designed to examine the effects of ET-1 (endothelin-1) and
      serum from PE (pre-eclamptic), HP (healthy pregnant) and HNP (healthy non
      pregnant) women on uterine arterial perfusion pressure and uterine contractility.
      Swine uteri (n = 25) were perfused for a period of up to 11 h, with the aim being
      to preserve a viable organ. Various concentrations of ET-1 as well as serum from
      PE, HP and HNP women (n = 10 per group) were administered to the perfused swine
      uteri and IUP (intrauterine pressure) and IAP (intra-arterial pressure) were
      recorded. ET-1 produced dose-dependent increases in IUP and IAP. The ET-1
      concentration in serum was higher in serum from PE women than in HP and HNP women
      (P > 0.05). Administration of all serum samples had a contractile effect on the
      swine uterus, with the greatest effect being seen in HNP women (12.8 +/- 5.3
      mmHg), followed by PE (9.06 +/- 4.2 mmHg) and HP (6.1 +/- 4.1 mmHg) women.
      Statistically significant differences were observed between HNP and PE women (P =
      0.048), and PE and HP women (P = 0.021). Increases in IAP following
      administration of serum from PE women (48.8 +/- 20.0 mmHg) were significantly
      higher (P = 0.024) compared with the effect of serum from HP women (28.4 +/- 13.7
      mmHg). In conclusion, the findings show that serum from PE women has significant
      vasoconstrictive and oxytocic effects compared with serum from HP women. In pre
      eclampsia, the balance between vasorelaxing and vasoactive substances is
      disturbed.

PMID- 15859944
TI  - Sulphated glycoconjugates are powerful inhibitors of spermatozoa binding to the
      vitelline envelope in amphibian eggs.
AB  - BACKGROUND INFORMATION: In amphibians, the role of sulphated glycans has not been
      determined in spermatozoa-egg interaction, although they are known to be involved
      in other systems. In previous studies, it was found that, in Discoglossus pictus,
      a VE (vitelline envelope) glycoprotein of 63 kDa exhibits high homology to
      Xenopus laevis gp69/gp64 and to ZP2 of mammals. gp63 and a glycoprotein of 75 kDa
      are both capable of binding the spermatozoa in in vitro assays and, having
      similar peptide maps and different glycosylation, are probably two glycoforms of
      the same protein. RESULTS: In the present study, binding assays performed by
      treating dejellied eggs with metaperiodate suggest that hydroxy groups of sugars
      are not directly involved in spermatozoa-vitelline envelope binding. Competition
      assays between dejellied eggs and spermatozoa preincubated with dextran, dextran
      sulphate or fucoidan indicated that sulphated oligosaccharides have an inhibitory
      effect on spermatozoa binding. In similar competition assays, Le(x) (Lewis(x))
      trisaccharide 3'-sulphate inhibited spermatozoa binding to VE in contrast with 3'
      sialyl-Le(x) tetrasaccharide. Assays performed with gp75- or gp63-coated beads
      and spermatozoa treated with fucoidan or dextran sulphate indicated that
      sulphated oligosaccharides competitively inhibit spermatozoa binding to gp75
      coated beads, yet not to gp63-coated beads. Finally, solubilized VE digested with
      N-glycosidase F retains the inhibitory activity in spermatozoa-VE binding assays
      in contrast with VE treated with alpha-N-acetylgalactosaminidase. CONCLUSION: It
      was concluded that VE sulphate groups are involved in spermatozoa binding. These
      groups are present in gp75 glycoconjugates and are probably located in O-linked
      glycoconjugates.

PMID- 15859945
TI  - Expression and function of semaphorin 7A in bone cells.
AB  - BACKGROUND INFORMATION: Sema-7A is a glycosylphosphatidylinositol-anchored
      semaphorin that was first identified in the immune system. It is a member of a
      large family of proteins involved in axon guidance signalling. Sema-7A is
      expressed in the myeloid and the lymphoid lineage and seems to be involved in
      cytokine expression and chemotaxy through its receptor Plexin C1. However, it can
      promote axon outgrowth, acting through a beta1 subunit-containing integrin
      receptor. RESULTS AND CONCLUSIONS: In the present study, we have investigated its
      regulation and function in bone cells. Semiquantitative reverse transcriptase-PCR
      demonstrated that Sema-7A mRNA is present during all stages of osteoblast
      differentiation and maturation in mouse calvaria cells and in MC3T3 cell line in
      vitro. Its expression is also regulated during primary osteoclast differentiation
      in vitro. We report that Sema-7A is capable of increasing the migration of MC3T3
      cells and that this process is mediated by the mitogen-activated protein kinase
      pathway in osteoblasts, probably through the integrin subunit beta1. Moreover,
      the addition of recombinant soluble Sema-7A to the culture enhances osteoclast
      fusion. These findings indicate for the first time the possible involvement of
      Sema-7A in bone cell differentiation.

PMID- 15859946
TI  - Expression of functionally phagocyte-type NAD(P)H oxidase in pericytes: effect of
      angiotensin II and high glucose.
AB  - BACKGROUND INFORMATION: A growing body of evidence demonstrates the involvement
      of the oxidative stress in the development of vascular complications associated
      with diabetes, such as hypertension, retinopathy, nephropathy, neuropathy and
      atherosclerosis. However, the molecular mechanisms accountable for the increased
      production of reactive oxygen species (ROS) remain uncertain. Among others, the
      NAD(P)H oxidase is one of the most important sources of superoxide anion (O2-)
      that induce dysfunction of vascular cells. Pericytes (PCs) have an essential role
      in the capillary dysfunction in retinopathy and other vascular complications in
      diabetes. We questioned whether PCs express a functional phagocyte-type NAD(P)H
      oxidase, and examined the role of angiotensin II and high glucose on the activity
      of the oxidase complex and expression of the essential subunit p22(phox).
      RESULTS: The mRNA expression of p22(phox), p47(phox), p67(phox) and NOX 1
      subunits, and the lack of gp91(phox) component, were detected in PCs by reverse
      transcriptase PCR. Western-blotting analysis demonstrated the protein expression
      of p22(phox), p47(phox) and p67(phox) subunits. As compared with the normal
      condition, stimulation of PCs with angiotensin II or high glucose induced: (i) an
      increase in ROS production and NAD(P)H oxidase activity, and (ii) an up
      regulation of p22(phox) mRNA and protein expression. CONCLUSIONS: Taken together,
      the present study provides the first evidence that PCs express a functional
      phagocyte-type NAD(P)H oxidase, which is up-regulated by both angiotensin II and
      high glucose. Given the importance of ROS in vascular physiology and pathology,
      the NAD(P)H oxidase complex could be an important therapeutic target in the
      treatment of microvascular disorders.

PMID- 15859947
TI  - Phosphoinositide 3-kinase is involved in the glucagon-induced translocation of
      aquaporin-8 to hepatocyte plasma membrane.
AB  - BACKGROUND INFORMATION: PI3K (phosphoinositide 3-kinase) mediates several signal
      transduction pathways in hepatocytes, including some involved in the regulation
      of vesicle trafficking. Hepatocytes express the water channel AQP8 (aquaporin-8)
      predominantly in an intracellular location, and it redistributes to the
      canalicular membrane, upon stimulation with the hormone glucagon, by a
      cAMP/protein kinase A-dependent mechanism. Since glucagon is capable of
      stimulating PI3K activity in hepatocytes and a cross talk between cAMP and PI3K
      has been suggested, in the present study, we examine whether PI3K activation is
      involved in the glucagon-induced translocation of AQP8. RESULTS: By quantitative
      immunoblotting of purified hepatocyte plasma membranes, we found that the
      preincubation of cells with two structurally different PI3K inhibitors,
      wortmannin or LY294002, prevented the glucagon-induced translocation of AQP8 to
      hepatocyte plasma membrane. Confocal immunofluorescence microscopy in cultured
      hepatocytes confirmed the dependence of the hormone-induced redistribution of
      AQP8 on PI3K activity. Functional studies showed that the PI3K inhibitors were
      also capable of preventing the glucagon-induced increase in hepatocyte osmotic
      membrane water permeability. CONCLUSIONS: Our results suggest that PI3K
      activation is involved in the glucagon-dependent signal transduction pathways
      leading to hepatocyte AQP8 translocation.

PMID- 15859948
TI  - Volume regulation in cortical collecting duct cells: role of AQP2.
AB  - BACKGROUND INFORMATION: The renal CCD (cortical collecting duct) plays a role in
      final volume and concentration of urine by a process that is regulated by the
      antidiuretic hormone, [arginine]vasopressin. This hormone induces an increase in
      water permeability due to the translocation of AQP2 (aquaporin 2) from the
      intracellular vesicles to the apical membrane of principal cells. During the
      transition from antidiuresis to diuresis, CCD cells are exposed to changes in
      environmental osmolality, and cell-volume regulation may be especially important
      for the maintenance of intracellular homoeostasis. Despite its importance, cell
      volume regulation in CCD cells has not been widely investigated. Moreover, no
      studies have been carried out till date to evaluate the putative role of AQPs
      during this process in renal cells. RESULTS: In the present study, we have
      studied the regulatory cell-volume responses to hypo-osmotic or hyperosmotic
      challenges in two CCD cell lines: one not expressing AQPs and the other stably
      transfected with AQP2. We have used a fluorescent probe technique in which the
      acquisition of single-cell kinetic data can be simultaneously recorded with the
      intracellular pH. Experiments with hyperosmotic mannitol media demonstrated that,
      independent of AQP2 expression, CCD cells shrink but fail to show regulatory
      volume increase, at least under the studied conditions. In contrast, under hypo
      osmotic shocks, regulatory volume decrease occurs and the activation of these
      mechanisms is more rapid in AQP2 transfected cells. This regulatory response
      takes place in parallel with intracellular acidification, which is faster in
      cells expressing AQP2. The acidification and the initial regulatory volume
      decrease response were inhibited by glibenclamide and BaCl2 only in AQP2 cells.
      CONCLUSIONS: These results suggest that increases in the osmotic water
      permeability due to the expression of AQP2 are critical for a rapid activation of
      regulatory volume decrease mechanisms, which would be linked to cystic fibrosis
      transmembrane conductance regulator and to barium-sensitive potassium channels.

PMID- 15859949
TI  - Tonoplast vesicles of Beta vulgaris storage root show functional aquaporins
      regulated by protons.
AB  - BACKGROUND INFORMATION: Water is crucial for plant development and growth, and
      its transport pathways inside a plant are an ongoing topic for study. Plants
      express a large number of membrane intrinsic proteins whose role is now being re
      evaluated by considering not only the control of the overall plant water balance
      but also in adaptation to environmental challenges that may affect their
      physiology. In particular, we focused our work on water movements across the root
      cell TP (tonoplast), the delimiting membrane of the vacuole. This major organelle
      plays a central role in osmoregulation. RESULTS: An enriched fraction of TP
      vesicles from Beta vulgaris (red beet) storage roots obtained by a conventional
      method was used to characterize its water permeability properties by means of the
      stopped-flow technique. The preparation showed high water permeability (485
      microm x s(-1)), consistent with values reported in the literature. The water
      permeability was strongly blocked by HgCl(2) (reduced to 16%) and its energy
      activation was low. These observations allow us to postulate the presence of
      functional water channels in this preparation. Moreover, Western-blot analysis
      demonstrated the presence of a tonoplast intrinsic protein. With the purpose of
      studying the regulation of water channels, TP vesicles were exposed to different
      acidic pH media. When the pH of a medium was low (pH 5.6), the water permeability
      exhibited a 42% inhibition. CONCLUSIONS: Our findings prove that although almost
      all water channels present in the TP vesicles of B. vulgaris root are sensitive
      to HgCl(2), not all are inhibited by pH. This interesting selectivity to
      acidification of the medium could play a role in adapting the water balance in
      the cell-to-cell pathway.

PMID- 15859950
TI  - Pore selectivity analysis of an aquaglyceroporin by stopped-flow
      spectrophotometry on bacterial cell suspensions.
AB  - Background information. Transport of water and small neutral solutes across
      plasma membranes is facilitated by AQP (aquaporin) and aquaglyceroporin channels,
      which belong to the MIP (major intrinsic protein) family. So far, more than 800
      MIP proteins have been identified on the basis of sequence homology, but only
      less than 10% of them have been functionally characterized. In most studies, the
      channel properties of MIP proteins have been determined by using Xenopus oocyte
      swelling assays or stopped-flow spectrophotometry on proteoliposomes. As both
      methods sometimes present disadvantages, we developed an alternative method for
      analysing MIP function.Results. The kinetics of plasmolysis or deplasmolysis of
      Escherichia coli cells in suspension, in response to osmotic challenges, was
      analysed by stopped-flow spectrophotometry. Cytoplasmic volume variations were
      monitored either by GFP (green fluorescent protein) fluorescence quenching or by
      90 degrees scattered light. The single exponential response to up-shocks in the
      impermeant solute mannitol was strongly accelerated when the cells expressed the
      native E. coli AQP AqpZ (rate constant 37.24 versus 3.05 s(-1) for control
      cells). The responses to hyperosmotic shocks realized with glycerol were
      biphasic. First, a light-scattering increase corresponded to cell plasmolysis.
      Secondly, deplasmolysis occurred when glycerol entered into the cell. Both phases
      were accelerated when the aquaglyceroporin GlpF was present in cell membranes. We
      concluded that the behaviour of MIP-expressing bacteria in the stopped-flow
      system was qualitatively identical with that reported for MIP-expressing oocytes
      or MIP-containing proteoliposomes. We then used this system to analyse the
      effects of mutations in the pore constriction of Gla(Llac), the aquaglyceroporin
      from Lactococcus lactis. In the present study, we show that Gla(Llac) loses its
      ability to transport glycerol but retains its ability to transport water when
      Val(223) was replaced by a histidine, the residue at the equivalent position in
      strict AQPs.Conclusions. These results show that stopped-flow spectrophotometry
      performed on E. coli cell suspensions is a useful experimental system to analyse
      the selectivity of wild-type or mutant MIP proteins and that a bifunctional
      aquaglyceroporin switches to an AQP by a single amino acid mutation in the pore
      constriction.

PMID- 15859952
TI  - Expression and subcellular localization of the AQP8 and AQP1 water channels in
      the mouse gall-bladder epithelium.
AB  - BACKGROUND INFORMATION: Transepithelial transport of water is one of the most
      distinctive functions by which the gall-bladder rearranges its bile content.
      Water is reabsorbed from the gall-bladder lumen during fasting, whereas it is
      secreted into the lumen following meal ingestion. Nevertheless, the molecular
      mechanism by which water is transported across the gall-bladder epithelium
      remains mostly unclear. RESULTS: In the present study, we investigate the
      presence and subcellular localization of AQP (aquaporin) water channels in the
      mouse gall-bladder epithelium. Considerable AQP8 mRNA was detected in the gall
      bladder epithelium of mouse, calf, rabbit, guinea pig and man. Studies of
      subcellular localization were then addressed to the mouse gall-bladder where the
      transcript of a second AQP, AQP1, was also detected. Immunoblotting experiments
      confirmed the presence of AQP8 and AQP1 at a protein level. Immunohistochemistry
      showed intense expression of AQP8 and AQP1 in the gall-bladder epithelial cells
      where AQP8 was localized in the apical membrane, whereas AQP1 was seen both in
      the apical and basolateral membranes, and in vesicles located in the subapical
      cytoplasm. CONCLUSIONS: The pattern of subcellular distribution of AQP8 and AQP1
      strongly corroborates the hypothesis of a transcellular route for the movement of
      water across the gall-bladder epithelium. Osmotic water would cross the apical
      membrane through AQP8 and AQP1, although AQP1 would be the facilitated pathway
      for the movement of water across the basolateral membrane. The presence of two
      distinct AQPs in the apical membrane is an unusual finding and may relate to the
      membrane's ability both to absorb and secrete fluid. It is tempting to
      hypothesize that AQP1 is hormonally translocated to the gall-bladder apical
      membrane to secrete water as in the bile duct epithelium, a functional homologue
      of the gall-bladder epithelium, whereas apical AQP8 may account for the
      absorption of water from gall-bladder bile.

PMID- 15859953
TI  - Novel human-derived cell-penetrating peptides for specific subcellular delivery
      of therapeutic biomolecules.
AB  - Short peptide sequences that are able to transport molecules across the cell
      membrane have been developed as tools for intracellular delivery of therapeutic
      molecules. This work describes a novel family of cell-penetrating peptides named
      Vectocell peptides [also termed DPVs (Diatos peptide vectors)]. These peptides,
      originating from human heparin binding proteins and/or anti-DNA antibodies, once
      conjugated to a therapeutic molecule, can deliver the molecule to either the
      cytoplasm or the nucleus of mammalian cells. Vectocell peptides can drive
      intracellular delivery of molecules of varying molecular mass, including full
      length active immunoglobulins, with efficiency often greater than that of the
      well-characterized cell-penetrating peptide Tat. The internalization of Vectocell
      peptides has been demonstrated to occur in both adherent and suspension cell
      lines as well as in primary cells through an energy-dependent endocytosis
      process, involving cell-membrane lipid rafts. This endocytosis occurs after
      binding of the cell-penetrating peptides to extracellular heparan sulphate
      proteoglycans, except for one particular peptide (DPV1047) that partially
      originates from an anti-DNA antibody and is internalized in a caveolar
      independent manner. These new therapeutic tools are currently being developed for
      intracellular delivery of a number of active molecules and their potentiality for
      in vivo transduction investigated.

PMID- 15859954
TI  - Size matters--in rectal cancer.

PMID- 15859955
TI  - A meta-analysis of the association of physical activity with reduced risk of
      colorectal cancer.
AB  - BACKGROUND: Physical activity may be associated with reduced risk of colorectal
      cancer. The main aim of this paper is to review the available evidence for a link
      between exercise and large bowel cancer. METHODS: A Cochrane-type methodology was
      performed. Data extracted included, type of study, type of physical activity
      measured and the numerical results. The risk ratios (RR) of the studies have been
      pooled according to the type of study, type of exercise, type of cancer and sex.
      Pooling was undertaken using fixed effect meta-analysis. A random effect meta
      analysis was used where substantial heterogeneity existed. RESULT: Data from 19
      cohort studies showed a statistically significant reduction in the risk of colon
      cancer in physically active males, RR being 0.79 (95% CI 0.72-0.87) and 0.78 (95%
      CI 0.68-0.91) for occupational and recreational activities, respectively. In
      women only recreational activities are protective against colon cancer (RR =
      0.71, 95%CI 0.57-0.88). Case-control studies showed significantly reduced risks
      of colon cancer in both sexes irrespective of the type of activity. No protection
      against rectal cancer is seen in either sex. CONCLUSION: There is considerable
      evidence that physical activity is associated with reduced risk of colon cancer
      in both males and females.

PMID- 15859956
TI  - The role of prophylactic oophorectomy in women undergoing surgery for colorectal
      cancer.
AB  - BACKGROUND: Current gynaecological practice is to remove surgically accessible
      ovaries with prior consent in post menopausal women to eradicate the risk of
      subsequent development of ovarian cancer. However in colorectal surgery opinion
      is divided, although evidence suggests that ovarian metastases from colorectal
      adenocarcinoma occur in 3-4% of cases. METHODS: The review is based on published
      literature of the role of prophylactic oophrectomy in women undergoing surgery
      for colorectal cancer, obtained from Medline/PubMed and other online databases
      using the terms 'prophylactic oophorectomy' and 'colon cancer'. Additional
      references were sourced by manually searching bibliographies of articles located.
      RESULTS AND CONCLUSION: There is a paucity of published information and published
      reports have conflicting conclusions. A preliminary report of a randomised
      prospective trial suggests the probability of increased recurrence free survival
      in the oophorectomy group. It would seem appropriate to consider the necessity
      and possible benefits of oophorectomy in women prior to surgery for colorectal
      cancer. This would seem particularly relevant in distal sigmoid or upper rectal
      cancers when the ovaries or uterus may be directly invaded and curative surgery
      would involve en bloc resection. Post menopausal women with a family history of
      ovarian cancer should be advised to have oophorectomy.

PMID- 15859957
TI  - Long-term outcomes of restorative proctocolectomy for Crohn's disease and
      indeterminate colitis.
AB  - INTRODUCTION: The present study aims to evaluate the short-term and long-term
      outcomes of patients undergoing restorative proctocolectomy (RPC) for Crohn's
      disease (CD) and Indeterminate colitis (IC) and to identify factors associated
      with adverse outcomes. METHODS: A descriptive study of 52 patients with CD or IC
      from a total of 1652 patients undergoing primary or salvage RPC in a single
      tertiary referral centre between 1978 and 2003. Primary outcomes were ileal pouch
      failure (excision or indefinite diversion), adverse events and functional
      outcomes (bowel frequency, urgency and continence). RESULTS: Patients with IC or
      IC favouring ulcerative colitis (Group 1, n = 26) had a pouch failure rate of
      11.5%vs 57.5% for patients with CD or IC favouring CD (Group 2, n = 26). Pouch
      salvage surgery was undertaken in 15 patients with a 13.3% failure rate. Patients
      in Group 2 were 2.6 times more likely (95% CI: 0.96-7. No significant differences
      were evident between CD and IC patients with regards to pelvic sepsis (19.2%vs
      15.4%), anastomotic stricture (23.1%vs 21.7%), small bowel obstruction (26.9%vs
      26.9%) or pouchitis (15.4%vs 11.5%). The 24-h bowel frequency (7.5 vs 8), faecal
      urgency, daytime or night time incontinence were similar between patients with CD
      or IC..17) to develop a pouch-related fistula than patients in Group 1.
      DISCUSSION: Crohn's disease and to a great extent indeterminate colitis favouring
      CD were both associated with high failure rates and postoperative pouch-related
      fistula rates. Despite these problems, functional outcomes for patients with CD
      or IC were similar. Patients with IC should remain candidates for RPC but careful
      pre-operative assessment is advised to exclude clinical signs favouring the
      diagnosis of CD. The complications associated with failure are extensive and the
      option of reconstructive surgery in patients with CD should be questioned.

PMID- 15859958
TI  - Ileostomy for constipation: long-term postoperative outcome.
AB  - BACKGROUND AND AIMS: Idiopathic constipation is a rare indication for ileostomy
      construction. The aim of the study was to evaluate the success of ileostomy in
      treatment of severe constipation. Also to analyse the surgical complications and
      re-operation rate to identify any factors potentially predictive of outcome.
      PATIENTS AND METHODS: This retrospective study analysed the long-term outcome of
      24 ileostomies constructed for constipation. The ileostomy construction was
      performed in 13 patients during large bowel/rectum resection, in 6 after a full
      laparotomy and in 5 through an abdominal wall trephine alone. We analysed the
      surgical complications and the re-operation rate according any factors
      potentially predictive of outcome. RESULTS: One (4%) patient had persistent
      constipation after stoma creation. Surgical complications occurred in 11 (46%):
      retraction in 6 (25.0%), peristomal sepsis in 3 (12.5%) and parastomal hernia in
      2 (8.1%). Refashioning of the stoma was necessary in 7 (29%) patients. Previous
      abdominal surgery, end ileostomy, ileostomy constructed after large bowel
      resection or laparotomy were associated with a significantly higher incidence of
      stomal complications while age, duration of follow up, major complication and
      ileostomy created after bowel resection were associated to a significantly higher
      re-operation rate (P < 0.05). Multivariate analysis identified end ileostomy and
      ileostomy created after bowel resection as independent risk factors for surgical
      complication and re-operation, respectively (P < 0.05). CONCLUSIONS: Ileostomies
      were associated with a high frequency of complications, but most could be managed
      by minor surgical interventions. Patients who are considered for an ileostomy for
      severe idiopathic constipation should, where possible, have a loop ileostomy
      through a trephine rather than a laparotomy.

PMID- 15859959
TI  - Colorectal intervention as part of surgery for patients with gynaecological
      malignancy.
AB  - OBJECTIVE: This study was conducted to determine the indications for and outcome
      of colorectal intervention in patients with advanced gynaecological malignancy.
      METHODS: Between January 1999 and June 2004, 27 gynaecological cancer patients
      underwent 36 colorectal intervention performed by general surgeons. The 36
      operations were associated with 14 (39%) primary surgical procedures, 9 (25%)
      second-look laparotomies, and 13 (36%) procedures for recurrence or palliation.
      RESULTS: The mean age was 56 years (range 32-83 years). The majority of
      operations were performed in patients with ovarian (67%), endometrial (18%) and
      cervical (15%) malignancy. The primary indications for colorectal resection was
      tumour cytoreduction in 56% of the 36 operations. Other indications included
      repair of iatrogenic bowel injuries (n = 9, 25%), resection for multiple
      iatrogenic enterotomies (n = 4, 11%), and bowel obstruction (n = 3, 8%). The most
      frequently performed bowel operation was rectosigmoid resection with end-to-end
      anastomosis (n = 19, 53%). Colostomy was performed in 14% of the rectosigmoid
      resections at primary surgery. Small-bowel resection was required in 31% of the
      36 operations. Postoperative complications included wound complications (14%),
      pulmonary infections (8%), cardiac complications (6%) and intra-abdominal abscess
      (6%). There was a single surgical mortality (3%). CONCLUSION: Colorectal
      intervention is frequently indicated during operations for advanced
      gynaecological malignancy, and they are associated with a significant rate of
      postoperative complications. Specialists operating on gynaecological malignancy
      should have the technical skills necessary to perform these procedures.

PMID- 15859960
TI  - MRI assessment of the bony pelvis may help predict resectability of rectal
      cancer.
AB  - OBJECTIVE: The outcome after surgical treatment of rectal cancer may be
      influenced by the technical difficulty of the operation, which is thought to be
      affected by pelvic size. The aim of this study was to examine the association
      between bony pelvic dimensions and CRM involvement. PATIENTS AND METHODS: All
      patients with primary rectal cancer between December 1999 and January 2002 were
      studied. Staging was performed by pelvic MRI. Nine pelvic dimensions were
      measured from the MR images on a workstation. Pathology reports were obtained for
      all patients and the mesorectal specimen was examined. Technical difficulty was
      assessed by circumferential resection margin (CRM) involvement. RESULTS: Of 126
      patients with primary rectal cancer, 88 had staging MRI and rectal excision;
      there were significant differences between the sexes in all 9 pelvic dimensions
      (P < 0.05). In females, the interspinous diameter was significantly shorter in
      patients with CRM involvement compared with patients with a negative CRM. In
      female patients predicted to have a negative CRM, the anteroposterior diameter of
      the inlet, the anteroposterior diameter of the midplane and the transverse
      diameter of the midplane (interspinous distance) were significantly shorter in
      patients who actually had a positive CRM compared with those in whom the CRM was
      negative. In male patients, there was no correlation between pelvic dimensions
      and CRM status. CONCLUSIONS: In certain patients with rectal cancer, CRM
      positivity may be predicted from pre-operative MRI pelvic measurements. This may
      influence the choice of adjuvant therapy.

PMID- 15859961
TI  - Fast-track barium enema: meeting the two-week wait rule for patients with
      suspected colorectal cancer.
AB  - OBJECTIVES: To meet the introduction of the two-week wait (TWW) rule for patients
      with suspected colorectal cancer, a fast-track barium enema (FTBE) service was
      set up. This study was conducted to evaluate the success of this approach in
      preparation for meeting the forthcoming targets on waiting times to treatment
      from referral and diagnosis. METHODS: All patients were offered a double-contrast
      barium enema within two-weeks, except those with a palpable rectal mass. FTBE
      were double-reported by specialist gastrointestinal radiologists. Patients with a
      suspected malignancy were booked for an urgent staging CT and outpatient
      appointment, whilst the remaining patients were referred back to their general
      practitioner with a report. Prospective data were collected and two 16-month
      periods analysed. RESULTS: Three hundred and nine patients had a FTBE over the
      first 16-month period and 277 (89.6%) were seen within two-weeks. Mean times from
      initial referral to staging CT and first outpatient appointment were 30.7 and
      36.0 days, respectively. Cancer was confirmed histologically in 32 (10.4%)
      patients. Of 267 patients without a malignancy, 46 (17.2%) were referred back to
      the colorectal outpatient or endoscopy service within 6-months. The number of
      referrals increased with time from a mean of 19.3 per month in the first period
      to 27.8 in the second, but the percentage with a suspected malignancy remained
      similar at 13.6% and 10.1%, respectively. CONCLUSION: FTBE diagnosed malignancy
      accurately and facilitated rapid staging. The TWW target was met in almost 90% of
      patients, whilst the impact on the colorectal outpatient and endoscopy service
      was minimized.

PMID- 15859962
TI  - A survey of perceptions and attitudes among European surgeons towards the
      clinical impact and management of postoperative ileus.
AB  - OBJECTIVE: Postoperative ileus (POI) can negatively affect patient recovery and
      morbidity, yet the lack of an internationally accepted definition and clinical
      management pathway for this condition suggest POI may be under-recognized as a
      clinical problem. The purpose of this survey was therefore to assess current
      attitudes of surgeons towards the clinical impact and management of POI. SUBJECTS
      AND METHODS: Telephone interviews were conducted with 230 surgeons from hospitals
      in the UK, France, Germany, Italy and Spain. RESULTS: Across Europe, there are
      differences in the terms surgeons use to refer to delayed recovery of
      gastrointestinal (GI) function and the symptoms, concerns and risks they
      associate with this condition. Furthermore, there is marked variation in the
      attitudes of European surgeons towards minimizing the risk of delayed recovery of
      GI function and in the strategies to manage POI. Additionally, some of the
      measures applied most commonly by European surgeons are in contrast to evidence
      in the literature indicating that they have no benefit for quicker resolution of
      GI function. CONCLUSION: The results suggest that there is a need for clearer
      definition of the factors that constitute POI, increased recognition of the
      impact of this condition and improved understanding of the most effective peri
      /postoperative care for surgical patients.

PMID- 15859963
TI  - Bowel function following insertion of self-expanding metallic stents for
      palliation of colorectal cancer.
AB  - OBJECTIVE: Self-expanding metallic stents (SEMS) are an important addition to the
      treatment of large bowel obstruction. The aim of this study was firstly to assess
      bowel function following SEMS placement and secondly to identify any potential
      factors which might aid in the prediction of technical failure of stent
      insertion. METHODS: A review of all patients undergoing attempted SEMS placement
      for palliation of malignant left-sided colorectal obstruction over a four-year
      period (1st May 2000-30th April 2004) was performed. RESULTS: Twenty-one patients
      (12 male) with a median age of 76 years (range 48-92 years) were included, 11
      with metastatic disease and 10 severe comorbidity. SEMS insertion was technically
      successful in 16 (76%) of 21 cases. Contrast successfully passed through the
      obstructing lesion in all 16 cases where SEMS placement was technically
      successful. It only passed through 1 of 5 cases where stenting was not possible
      (P = 0.0008, Fisher's Exact test). Complications included colonic perforation (1
      case), stent migration (1 case) and tumour ingrowth requiring a second stent (1
      case). Median survival after SEMS was 12 months (range 1-30 months), and 9
      patients died during follow-up. Median bowel frequency following SEMS was 3.5
      times per day (range 1-7). Eight patients always passed a liquid stool, 3 others
      regularly required laxatives and one further patient with poor function after
      stenting requested a defunctioning stoma. CONCLUSION: Failure of contrast to pass
      through the obstructing lesion may predict those cases where stenting will not be
      technically possible. Median survival following SEMS insertion is encouraging in
      this series, but bowel function is often poor. Expected bowel function should be
      discussed fully when consenting patients for a SEMS, particularly those with
      metastatic disease who are otherwise fit for resectional surgery.

PMID- 15859964
TI  - Variations in the evaluation of colorectal cancer risk.
AB  - OBJECTIVES: To test the variability in estimating cancer risk and demonstrate the
      consequences that subjectivity has on patient care. SUBJECTS AND METHODS: Forty
      three clinicians were each asked to assess 40 symptomatic colorectal referrals.
      Each clinician was provided with a comprehensive history on the 40 patients. The
      clinicians graded the referral according to a malignancy risk score, decided on
      the required first line investigation and the priority of that investigation. The
      main outcome measures used was accuracy in cancer detection and appropriateness
      of investigations selected. RESULTS: There was a wide degree of variation among
      all clinicians grading both benign and malignant disease with the overall correct
      classification of 54% (P-value of <0.001). On average, the clinicians correctly
      diagnosed 71.3% of the cancer patients as compared to 44% of the benign patients.
      Of the cancer patients, 47% were correctly classified as an urgent referral
      whilst 52% of the benign patients were over classified and graded as an urgent
      referral. The mean number chosen by clinicians to have a flexible sigmoidoscopy
      as the appropriate first investigation was 13 (of 40 patients); this was despite
      the diagnosis being possible in all cases with a flexible sigmoidoscopy. The
      choice to use full colonic investigation was seen throughout all disciplines.
      Junior doctors demonstrated the highest tendency choosing full colonic
      investigation in 92.3%. Consultants and senior grades showed the least tendency
      to choose full colonic imaging although even here colonoscopy or barium enema
      represented 48.5%. CONCLUSION: Subjective assessment of cancer referrals is a
      significant problem that needs to be confronted. Improvements are needed to
      resolve the inherent problems of subjectivity and operator bias if uniform
      quality of patient care and best use of resources is to be achieved.

PMID- 15859965
TI  - Impact of faecal incontinence severity on health domains.
AB  - OBJECTIVE: Faecal incontinence is a problem that can have a major impact on the
      quality of life of those affected. Our aim was to relate the severity of faecal
      incontinence to the impact on several general health domains. METHODS: Patients
      from a prospective diagnostic cohort study, performed in 16 medical centres in
      the Netherlands, were invited to the study. The severity of incontinence was
      determined with the Vaizey score, which ranges from 0 (continent) to 24 (totally
      incontinent). Based on their Vaizey score, patients were assigned to one of five
      severity categories. All patients completed the EuroQol-5D instrument, which
      evaluates the existence of problems on five health domains: mobility, self-care,
      usual activities, pain/discomfort and anxiety/depression. RESULTS: Data from 259
      consecutive patients (25 male) could be analysed. Their mean age was 59 years (SD
      +/- 12). The mean duration of faecal incontinence was 8.1 years (SD +/- 8). The
      proportion of patients reporting problems rose significantly with increasing
      severity of faecal incontinence in the domains of usual activities (ranging from
      36% in the least severe group to 71% in the most severe group (P < 0.001)),
      pain/discomfort (ranging from 35% to 60%; P = 0.025), and anxiety/depression
      (ranging from 23% to 49%; P = 0.037). No significant trends could be observed in
      the domains of mobility and self-care. CONCLUSION: There exists a significant
      relation between severity of incontinence and frequency of reported problems in
      the domains of usual activities, pain/discomfort and anxiety/depression.

PMID- 15859966
TI  - Colorectal cancer audit: a comparative study before and after establishing a
      specialty colorectal surgery unit.
AB  - OBJECTIVE: A prospective audit was kept for colorectal cancer after the
      establishment of a special-interest colorectal unit at a Melbourne metropolitan
      teaching hospital. METHODS: These data were compared with data collected
      retrospectively on surgical management of colorectal cancer by general surgeons
      in the hospital. RESULTS: The groups were well matched with respect to age, sex,
      pathological staging and elective vs urgent surgery. Differences were found in
      postoperative length of stay (9 vs 12 days, P = 0.01) in favour of the colorectal
      special interest group. Differences were found in the permanent stoma rate with
      regard to rectal cancer with the colorectal special interest group having a lower
      permanent stoma rate. CONCLUSION: Specialisation improved the results of
      treatment.

PMID- 15859967
TI  - Unreasonable expectations in emergency colorectal cancer surgery.
AB  - OBJECTIVES: The recently published ACPGBI colorectal cancer (ACPGBI CRC) scoring
      system for predicting operative mortality has been suggested as an instrument to
      improve patient consent procedures and to compare results between centres. This
      study compares the results of a surgical unit against the standards set by the
      ACPGBI colorectal cancer model and for emergency surgery, against the p-POSSUM
      instrument. METHODS: Data for the ACPGBI CRC model were collected prospectively
      through 2003 at the Leicester Royal Infirmary. Additional data needed for the p
      POSSUM was retrospectively collected from case records. The actual mortality was
      compared with that predicted by the models. RESULTS: Seventy-two colorectal
      cancer operations were performed during the study period. The observed operative
      mortality in elective cases was lower, and in emergency cases higher, than
      predicted by the ACPGBI CRC model. With emergency cases the predicted mortality
      using P-POSSUM was significantly higher than that using the ACPGBI CRC model,
      particularly in the presence of faecal contamination. CONCLUSION: The ACPGBI CRC
      model may be accurate for elective cases, but appears to significantly
      underestimate predicted mortality in the emergency setting, both actual and
      predicted by p-POSSUM. This may be due to a failure to incorporate adequate
      weighting for faecal peritonitis and the associated systemic insult into the
      ACPGBI model.

PMID- 15859968
TI  - Prospective analysis of stoma-related complications.
AB  - BACKGROUND: Stoma-related complication rates vary between 10% and 70%, possibly
      because of varying lengths of follow-up. It is thought that most of the
      complications improve with time. Furthermore, little is known about the commonly
      neglected but potentially quite distressing complications such as leakage,
      soiling and night-time emptying. The aim of this audit was to examine
      prospectively whether there was any difference in the complication rates at
      different time-points during the postoperative follow up period. METHOD: A
      prospective study on 408 consecutive patients with either colostomy or ileostomy
      was conducted over a period of at least 2 years. Both emergency and elective
      procedures were included. Stoma related complications were analysed at 10 days, 3
      months, 6 months, 1 year and 2 years postoperatively. RESULTS: Both elective and
      emergency stomas had similar complication rates. The percentage of patients who
      had stenosis (1-2%), retraction (8-22%), prolapse (1-3%) or odour (6-9%) did not
      significantly change with time. The complication rates for skin excoriation,
      leakage, soiling or night-time emptying were higher amongst the ileostomy
      patients, and these rates did not improve with time. The proportion of patients
      who had parastomal hernias increased with time (from 0 to 40% in the colostomy
      and 0 to 22% in the ileostomy group). Daytime leakage, night-time leakage,
      soiling and night-time emptying were more problematic in the ileostomy group.
      CONCLUSIONS: The proportion of patients who had postoperative stoma-related
      complications did not improve with time, but the rate of parastomal hernias in
      both groups and night-time emptying in the ileostomy group was worse with time.
      Ileostomy patients had a higher incidence of skin excoriation, leakage, soiling,
      and night-time emptying, and they should receive additional support.

PMID- 15859969
TI  - Diagnosis and treatment of enterovesical fistulae.
AB  - OBJECTIVE: Enterovesical fistulae are a recognized complication of a variety of
      inflammatory and neoplastic conditions. Despite advances in imaging and treatment
      the diagnosis may be delayed and the management remains diverse. We describe our
      experience with their diagnosis and management. PATIENTS AND METHODS: This
      retrospective study encompassed all patients referred over a 10-year period with
      clinical suspicion of or confirmed enterovesical fistula. Demographics, clinical
      presentation, aetiology and clinical outcome were evaluated. Mean follow-up was
      18 months (range 6-50 months). RESULTS: Thirty patients were studied. The mean
      age was 63.5 years (range 23-92 years). Fifteen (50%) patients presented with
      classical urinary symptoms (pneumaturia, faecaluria and recurrent urinary tract
      infections). The commonest investigations (n, % positive) included CT (15, 80),
      cystoscopy (16, 87.5), endoscopy (11, 54.5) and barium enema (8, 50). There were
      20 inflammatory and 10 neoplastic aetiologies. Five patients were treated
      conservatively and 25 patients underwent surgery. Surgery resulted in symptomatic
      cure in the majority of cases (22/25). CONCLUSION: Classical urinary symptoms
      were only evident in 50% of patients with confirmed fistulae. We advocate CT
      scanning as the optimum imaging modality before surgical intervention. Surgical
      treatment in a specialized unit remains the most effective treatment of
      enterovesical fistulae.

PMID- 15859970
TI  - Mesh repair of parastomal hernias--a safety modification.
AB  - INTRODUCTION: Parastomal herniation is not uncommon and numerous surgical
      approaches to the problem have been employed including mesh reinforcement. Bowel
      wall erosion is a worrying potential complication of placing an edge of mesh
      around bowel. To reduce this possibility a simple modification is suggested.
      METHOD: The polyproylene mesh repair is fashioned on the posterior rectus sheath.
      The required aperture for the bowel is marked appropriately on the mesh. Instead
      of simple removal of the marked circle, the aperture is fashioned by folding back
      and stitching in place the triangular flaps from the middle to form a rolled
      rather than sharp edge. Non-absorbable monofilament stitches reconstitute the
      mesh encirclement, and attach it laterally and medially to the aponeurotic
      tissue. A review of the case notes was conducted and each patient was contacted
      by a postal questionnaire. RESULTS: This technique has been used in 10 patients
      (7 end colostomies, 2 end ileostomies and 1 loop ileostomy) since 2000. Over a
      median follow-up period of 30 months (range 2 to 40 months) there have been no
      hernia recurrences, no infected meshes, no bowel damage attributable to the mesh
      and no troubles with stoma. The only complication encountered has been a segment
      of superficial wound breakdown in one patient. CONCLUSIONS: This technique
      appears to offer a safe and reliable modification for mesh repair of parastomal
      herniation, in being designed to obviate the possibility of erosion of the stomal
      bowel wall by a sharp mesh edge but at the same time providing a sound
      herniorrhaphy by complete encirclement.

PMID- 15859973
TI  - Hepatitis B virus vaccination of blood donors--what costs may be expected?
AB  - Although the risk of transfusion-transmitted hepatitis B virus (TT-HBV) infection
      is very low, it still exists. Therefore, introduction of further precautions to
      reduce this risk is discussed at present. However, so far no data are available
      about the HBV vaccination status among blood donors (BDs). We compared HBV
      vaccination status of apheresis donors (ADs) of a university based and whole BDs
      (WBDs) of a Red Cross blood donation service using a standardized questionnaire.
      On the basis of these data, the estimated costs over 10 years for HBV vaccination
      were calculated for two different strategies and compared with the costs for HBV
      nucleic acid amplification technology (NAT) testing. 22.3% of the WBDs and 41.2%
      of the ADs indicated having received at least one HBV vaccine dose. This
      difference was related to the different demographic structures of the two BD
      populations (BDPs). With regard to the primary costs for the blood donation
      service, HBV vaccination of BDs could be an alternative to HBV NAT testing,
      especially for BDPs with an already high HBV vaccination rate and a high donation
      frequency.

PMID- 15859974
TI  - Effects of a major earthquake on blood donor types and infectious diseases marker
      rates.
AB  - This observational study attempted to identify the effect of a natural disaster
      on the safety of blood supply and donor types with the influx of donors after a
      severe earthquake. Blood donation rate, blood discard rate and safety of blood
      donations responding to the earthquake, as projected from the infectious disease
      marker rate, were evaluated in blood donated immediately before (1 July-17
      August) and after 17 August 1999 (17 August-21 August). These were compared with
      the results from the corresponding periods in 1998 and 2000 for donations at a
      university medical centre and two regional blood centres. 8055 units of
      allogeneic blood were collected at two regional blood centres, and 450 units were
      collected at a university medical centre during 4 days. Viral marker rates were
      nearly the same at the former but were slightly lower at the latter. The blood
      discard rate was nearly twice the comparative periods at the former, but it
      remained unchanged at the latter. Voluntary donors replaced the replacement
      donors during 4 days. This analysis highlights the size of the pool of potential
      donors that are available as a national resource that can be motivated to give
      blood with the right motivation.

PMID- 15859975
TI  - Impact of introducing guidelines on anticoagulant reversal.
AB  - The production of clinical guidelines has become an accepted and lauded part of
      modern medicine. It is also widely perceived that these guidelines provide some
      sort of panacea for the problems that medicine faces. Our experience suggests
      otherwise. Triggered by on going anecdotal evidence of poor practice, we reviewed
      the effect on practice of a recently introduced local guideline on the management
      of major bleeding in patients on warfarin. Comparing 34 patients treated before
      and 48 patients after the introduction of the guideline, we found no significant
      improvement in prothrombin complex concentrate dosing or administration of
      vitamin K. The only improvement witnessed was in early assessment of the effect
      of the intervention on coagulation which improved from 10 to 35% of cases. Of
      major concern, in 10% of cases, there was no documentation to confirm or refute
      that prothrombin complex concentrate (PCC), which had been issued, had actually
      been administered to the patient. The production and widespread dissemination of
      this local guideline did not achieve significant improvement in clinical
      practice. Possible reasons for failure to adhere to the guideline are discussed.

PMID- 15859976
TI  - Topical treatment of ocular surface defects: comparison of the epitheliotrophic
      capacity of fresh frozen plasma and serum on corneal epithelial cells in an in
      vitro cell culture model.
AB  - Accelerated healing of ocular surface disorders was reported using serum for
      topical application. It is supposed that growth factors, fibronectin and vitamins
      in serum support the proliferation of corneal epithelial cells. The use of fresh
      frozen plasma (FFP) instead of serum is theoretically attractive, as it is more
      easily available from blood banks. In this study, serum and FFP were investigated
      for composition of epitheliotrophic factors and effect on corneal epithelial
      cells. Whole blood was taken from five donors. Serum and FFP were prepared, and
      the concentrations of epithelial growth factor (EGF), Platelet-derived growth
      factor (PDGF), transforming growth factor-beta1, fibronectin and vitamin A were
      determined. Immortalized human corneal epithelial cells were used to investigate
      growth, migration and differentiation in response to both blood products.
      Significant differences were found regarding the mediator composition of serum
      and FFP. Serum rather than FFP was significantly superior in stimulating cell
      growth, migration and differentiation. The epitheliotrophic capacity of blood
      products depends upon the composition of growth factors and vitamins. Blood
      clotting strongly influences the growth factor pattern. The superior
      epitheliotrophic capacity of serum might be due to the higher concentration of
      proliferation mediators such as EGF and PDGF and its higher content of vitamin A.

PMID- 15859977
TI  - Genotyping of human neutrophil antigen-5a (Ond).
AB  - Antibodies to human neutrophil alloantigens (HNA) can cause immune-mediated
      neutropenias and transfusion complications. The diagnosis of antibodies to the
      HNA-5a (Ond) isoform of the alphaLbeta2 integrin is hampered by the lack of
      reliable methods for HNA-5a antigen typing. We have devised a polymerase chain
      reaction sequence-specific primer method (PCR-SSP) and used it to determine the
      HNA-5a gene frequencies in 320 individuals from different ethnicities. 15.3% were
      found to be HNA-5a negative, with no significant deviation between the
      populations. Results of HNA-5a genotyping were in accordance with phenotyping.
      Availability of HNA-5a PCR-SSP will facilitate the diagnosis of Ond antibody
      mediated clinical conditions.

PMID- 15859978
TI  - Frequency distribution of human platelet antigens in the Indian population.
AB  - This study was undertaken with an aim of establishing the frequency distribution
      of various human platelet antigens (HPA) in Indian populations by means of DNA
      based technology. A total of 1164 people belonging to various population groups
      were studied for the frequency distribution of HPA. DNA extraction was performed
      from peripheral venous blood samples. Polymerase chain reaction allele-specific
      amplification technique was used for HPA genotyping. The HPA bands were
      visualized by using ethidium bromide-stained agarose gel, after electrophoresis.
      The homozygosity of the HPA-1b/1b genotype was found to be significantly higher
      (P < 0.05) in the Parsi population group and Vatalia Prajapati population group,
      compared to Maharashtrians. Frequency distribution of HPA-1b in our populations
      was found to be slightly lower than that reported in some western populations.
      This study has established a DNA technique to diagnose cases of NAITP
      definitively and to treat these cases during the neonatal period, and also gives
      the frequency distribution of HPA in some of the Indian population.

PMID- 15859979
TI  - Late onset neonatal anaemia due to maternal anti-Ge: possible association with
      destruction of eythroid progenitors.
AB  - There have been no reports of severe haemolytic disease of the newborn (HDN) due
      to Gerbich (Ge) antibodies. Two babies with HDN due to anti-Ge3, both born to the
      same mother, are described. The anti-Ge appeared in the first pregnancy and was
      not detectable in the first trimester, the babies' reticulocyte and bilirubin
      values were not greatly elevated (similar to HDN due to Kell antibodies), and the
      anaemia in both cases was either not apparent or not severe until 2 to 4 weeks
      after birth. Ge antigens are found on glycophorins (GPs) C and D; GPC, like Kell,
      has been shown to be expressed early on erythroid progenitor cells. The maternal
      anti-Ge3 was shown to promote phagocytosis of Ge+ early erythroid progenitors by
      monocytes (similar to what has been reported with anti-K and K+ progenitor
      cells). Thus, anti-Ge3 may cause immune destruction of erythroid progenitors and
      possibly suppression of erythropoiesis (which would explain the reticulocyte and
      bilirubin values seen in both cases). Anti-Ge3 appears to be capable of causing
      severe HDN. We suggest that babies born to mothers with anti-Ge should have their
      haemoglobin concentrations monitored for signs of anaemia for several weeks after
      birth. Functional assays may prove useful.

PMID- 15859980
TI  - Prevention of transfusion-transmitted hepatitis E by donor-initiated self
      exclusion.
AB  - Safety in blood transfusion has all along been focused on blood borne viruses
      like HIV, hepatitis B and C. However, infective agents that are not usually
      transmitted through blood may also pose risk to transfusion if the donor gives
      blood in the early-viraemic phase. A case report of potential transfusion
      transmitted hepatitis E (HEV) is described. It shows the virus can be
      transmissible via blood because of the presence of HEV RNA in the blood donated.
      Pre-donation health screening was unable to exclude this asymptomatic donor. But
      donor-initiated call back system which acts as an additional safety net prevented
      the release of the potential infective blood products.

PMID- 15859981
TI  - Characterization of the humoral immune response in two paediatric patients
      transplanted with split livers from ABO-incompatible living-related donors:
      appearance of cytomegalovirus-induced ABO antibodies.
AB  - Two blood group O paediatric patients, 12 and 6 months old, were transplanted
      with liver segments from their blood group A2Le (a(-)b+) Se and blood group A1Le
      (a(-)b+) Se fathers, respectively. Recipient anti-A antibody titres were reduced
      prior to transplantation by blood exchange. Both patients had rejection episodes
      in the post-transplant period that were reversed by anti-rejection therapy. No
      anti-A antibody titre rise occurred concomitant with these rejections.
      Postoperatively both patients had cytomegalovirus (CMV) infections, and
      simultaneous with these infections, a strong increase in anti-A antibody titres
      was seen, but no rejection occurred. The anti-A antibody titre increase seemed to
      be specific for A antigens, because the anti-B and anti-alphaGal (anti-pig)
      antibody titres did not show any changes. CMV infection is a serious cause of
      morbidity and mortality in immunosuppressed patients, and the virus can influence
      glycosylation of infected cells. Whether this can explain the importance of the
      infection in relation to the increase in titre remains to be elucidated.

PMID- 15859982
TI  - Recombinant FVIIa in the management of intracerebral haemorrhage in severe
      thrombocytopenia unresponsive to platelet-enhancing treatment.
AB  - Intracranial haemorrhage (ICH) is a dramatic and potentially life-threatening
      presentation of children with thrombocytopenia. Management is limited to
      supportive care. Recent evidence suggests that ongoing bleeding following the
      initial ICH may result in greater neurological morbidity and mortality.
      Haemostatic agents, including recombinant factor VIIa (rFVIIa), a product
      licensed for use in patients with haemophilia and inhibitors, may be helpful in
      reducing bleeding in children with refractory thrombocytopenia. We present the
      case of a 16-year-old girl with severe refractory immune thrombocytopenia, who
      presented with a major ICH and responded to treatment that included rFVIIa and
      platelet transfusions. The dose of rFVIIa was empirically chosen and based on
      reported cases in the literature. The case highlights a number of issues
      regarding off-label use of rFVIIa and demonstrates the need to prospectively
      collect accurate information on the off-label use of this new potentially useful
      medication.

PMID- 15859983
TI  - Managing passively acquired autoimmune neonatal neutropenia: a case study.
AB  - Pregnant women with autoimmune neutropenia (AIN) and circulating neutrophil
      specific autoantibodies can deliver neutropenic neonates at risk of sepsis. We
      report the case of a woman who had two such pregnancies. The woman had been on
      prophylactic granulocyte colony-stimulating factor (G-CSF) treatment, but this
      was ceased prior to conception in both pregnancies. In the first pregnancy, there
      was no monitoring or interventions, and the neonate was neutropenic and required
      intensive care treatment. In the second pregnancy, the maternal neutrophil
      autoantibody level was monitored, and G-CSF treatment was introduced in the third
      trimester. The second infant had no neutropenia at delivery and an excellent
      Apgar score. We discuss the management strategy in the second pregnancy that
      included monitoring of serial titres of the maternal autoantibody and the
      introduction of G-CSF in the third trimester, which may have contributed to a
      more favourable clinical outcome. This may assist other clinicians faced with
      similar dilemmas in the future.

PMID- 15859984
TI  - Use of red cells preserved in extended storage media for exchange transfusion in
      anti-k haemolytic disease of the newborn.
AB  - Anti-k is a Kell-related antibody. There is little correlation between the
      maternal antibody titre and the severity of haemolytic disease of the foetus and
      newborn, and anaemia is usually associated with low bilirubin levels. Severe
      erythroblastosis has been reported with a low titre anti-k (IAT 8-16). We report
      a case of severe haemolytic disease of the newborn (HDN) due to anti-k. HDN was
      associated with a normal bilirubin level and reticulocytopenia. The foetus was
      monitored by ultrasound, and delivery by elective caesarean section (CS) was
      planned. The mother was admitted 1 week before the expected date of delivery, and
      the infant was delivered by urgent CS. The infant required exchange transfusion.
      As suitable plasma-reduced (k antigen(-)) red cell units were not readily
      available, k- SAGM red cell units (preserved in extended storage media: SAGM
      sodium chloride, adenine, glucose and mannitol) were provided. The post
      transfusion Hb remained stable, and the infant did not require further
      transfusion support. Our findings (reticulocytopenia and normal bilirubin levels)
      support the hypothesis that the pathogenesis of anaemia and haemolysis in anti-k
      HDN may be similar to that in anti-K (suppression of erythropoesis and immune
      destruction of K+ erythroid progenitor cells by macrophages in the foetal liver).
      The ideal product for exchange transfusion is plasma-reduced RBC, less than 5
      days old. We provided a 4-day-old SAGM red cell unit for exchange transfusion in
      a term infant, and this was uneventful. Caution should be taken, however, and
      renal function and electrolyte levels should be monitored closely. More
      information is required regarding the safety of SAGM units for exchange
      transfusion.

PMID- 15859985
TI  - Relationships between parameters used for routine quality monitoring of platelet
      concentrates.

PMID- 15859988
TI  - Macro-video documentation patch tests.
AB  - An unequivocal distinction between allergic and irritant patch test reactions is
      often difficult with patch tests. This study was designed to evaluate the worth
      of video-macro camera documentation for differentiation between allergic and
      irritant test reactions and to investigate whether there are characteristic
      clinical differences in patch test responses between metal salts and fragrances.
      Patch testing was performed with nickel sulfate, fragrance mix and an irritant,
      sodium lauryl sulfate 1% aq., on the upper back of 82 patients, with evaluation
      and computer-aided video documentation after 48 and 72 hr. No reliable
      clinicomorphological criterion was found for assessing a weak patch test reaction
      as being definitely allergic. Even characteristic papules and vesicles were not
      regularly found in allergic reactions. However, unlike fragrance mix, patch test
      reactions to nickel sulfate were characteristic in that they showed a
      heterogeneous spread and an association with hair follicle openings, independent
      of reaction intensity. Evaluation based on additional computer-aided video-macro
      camera documentation did not add further advantage for the differentiation of
      allergic and irritant reactions. But well-defined clinicomorphological features
      and reaction patterns to single test substances or even whole substance
      categories could be helpful additional criteria for evaluating patch test
      responses in clinical practice.

PMID- 15859989
TI  - Allergic contact dermatitis from iodine preparations: a conundrum.
AB  - Iodine preparations are widely used antiseptics, yet limited information exists
      on their irritant potential and threshold for diagnostic patch testing. We
      examine this issue by using iodine in different preparations and concentrations.
      A total of 24 fair-skinned, healthy volunteers without a history of iodine
      allergy, ranging in age from 18 to 65 years (mean age 49.5 + 10.7 SD), were
      recruited. Concentrations of 0.5%, 1%, 5% and 10% iodine in petrolatum (pet.),
      0.5%, 0.75% and 1% iodine in 70% isopropyl alcohol (IPA) and 1%, 5%, 7.5% and 10%
      of povidone-iodine (PVP-I) were applied for 2 days to the intrascapular area on
      the back or to the volar forearm between cubital fossa and wrist using Finn
      Chambers on Scanpor. Test sites were read 2 days (D2) and 4 days (D4) after patch
      application. Skin reactions were graded according to the following scheme: 0 = no
      reaction, + = questionable erythema, 1 = definite erythema, 2 = erythema and
      induration and 3 = vesiculation. Mild-to-moderate reactions (+ to 2) were
      observed in 75% of the subjects patched with 5% iodine in pet. at 2-4 days after
      application. Almost all subjects reacted to 10% iodine at D2 and D4, with 65%
      exhibiting erythema and induration or vesiculation. A large number (33%) of the
      subjects developed some reactions to the low concentration (0.5%) of iodine in
      70% IPA at D2. Vesicles were seen in 54% of the subjects patched with 1% iodine
      in 70% IPA at D4. Only 1 subject reacted to 7.5% and 10% PVP-I. Iodine can be
      irritant to normal skin in pet. and in 70% IPA. Pet. possibly enhances skin
      contact with iodine, thus increasing its irritant capacity. Alcohol removes sebum
      from the skin surface, and it might increase iodine penetration into the skin,
      causing a higher degree of irritation. PVP-I is relatively non-irritant, because
      its iodine is complexed in an iodophor. For diagnostic patch testing, we
      recommend using iodine at less than 1% in pet. and at less than 0.5% in 70% IPA.
      For PVP-I, 10% appears non-irritant. With the variation in patch-test irritant
      response, interpretation of the patch-test response in the light of clinical
      history is mandatory.

PMID- 15859990
TI  - A clinical and patch test study of patients with positive patch test reactions to
      fragrance mix in China.
AB  - The clinical and patch test (PT) features of patients with positive PT reactions
      to fragrance mix (FM) were studied. 378 consecutive eczema outpatients patch
      tested with a modified European standard series were analysed. 60 patients
      (15.9%) reacted to FM. No significant differences could be found between the ages
      of FM PT-positive and PT-negative patients [median age 40.5 (range from 18 years
      to 69 years) versus median age 37.5 (range from 5 years to 81 years), rank sum
      test, P = 0.301]. FM PT-positive rate in confirmed non-cosmetic allergic contact
      dermatitis patients was 30.4%, which was similar to that in confirmed cosmetic
      allergic contact dermatitis patients (30.4% versus 30%, chi(2) test, chi(2) =
      0.0010, P = 0.972). The FM PT-positive rates were 10.8% in males and 18.2% in
      females (chi(2) test, chi(2) = 3.3443, P = 0.067). 76.7% of the patients with
      fragrance contact dermatitis were allergic to Chinese traditional medicine, which
      is much higher than that for cosmetic allergy (76.7% versus 43.3%, chi(2) test,
      chi(2) = 6.9446, P = 0.008). The positive PT rate to colophonium in the patients
      with positive PT reactions to FM is higher than that in the FM PT-negative
      patients (18.9% versus 3.0%, chi(2) test, chi(2) = 15.5471, P < 0.01). 62.5% of
      the patients reacted to colophonium were positive to FM. These results show that
      age has little effect on fragrance contact allergy. Other fragrant products
      besides cosmetics are also important sources of fragrance contact allergy.
      Chinese traditional medicine was an important factor in fragrance allergy in
      China. Patients with positive PT reactions to FM are more likely to react to
      colophonium.

PMID- 15859991
TI  - Contact allergy to gold in patients with gold-plated intracoronary stents.
AB  - An increasingly common and effective method for the treatment of atherosclerotic
      disease in the coronary arteries is percutaneous transluminal coronary
      angioplasty (PTCA) and stenting. The stents are made of different metals. An
      increased rate of restenosis when using gold-plated stents has been shown.
      Contact allergy to gold is common in many countries. Recently, a study has shown
      an increased rate of contact allergy to nickel among patients with restenosis and
      a nickel-containing stent. The aims of our study were to investigate whether
      there was an increased rate of contact allergy to gold among patients with gold
      plated stents and if this increased the risk of restenosis. 22 patients who had
      received a gold-plated stent were patch tested. An age- and sex-matched
      population of 88 patients, previously patch tested because of a suspected contact
      dermatitis, served as controls. In the stent group, 10/22 (45.5%) had a contact
      allergy to gold, in the control group 18/88 (20.5%); the difference is
      statistically significant (P = 0.04). There was no significant difference
      regarding frequency of restenosis. Our study indicates that there is a risk of
      sensitizing the patient when implanting a gold-plated stent. Further studies are
      needed to confirm these results and to evaluate whether there is an increased
      risk of restenosis.

PMID- 15859992
TI  - Quantitative patch and repeated open application testing in methyldibromo
      glutaronitrile-sensitive patients.
AB  - Contact allergy to methyldibromo glutaronitrile (MDBGN), often combined with
      phenoxyethanol (PE) (e.g., Euxyl K 400), increased throughout the 1990s in
      Europe. Consequently, in 2003, the European Commission banned its use in leave-on
      products, where its use concentration was considered too high and the non
      sensitizing use concentration as yet unknown. The 2 objectives of the study are
      (a) to find a maximum non-eliciting concentration in a leave-on product in
      MDBGN/PE-sensitized patients, which could possibly also be considered safe
      regarding induction and (b) to find the best patch test concentration for MDBGN.
      We, therefore, performed a use-related test (ROAT) in patients sensitized to
      MDBGN/PE (n = 39) with 3 concentrations of MDBGN/PE (50, 100 and 250 p.p.m.
      MDBGN, respectively). A subset of these patients (n = 24) was later patch-tested
      with various concentrations (0.1, 0.2, 0.3 and 0.5% MDBGN, respectively). 15
      patients (38%, 95% confidence interval (CI) = 23-55%) had a negative and 24 (62%;
      95% CI = 45-77%) a positive overall repeated open application test (ROAT) result.
      13 reacted to the lowest (50 p.p.m.), 8 to the middle (100 p.p.m.) and 3 to the
      highest concentration (250 p.p.m.) only. In those 13 reacting to the lowest ROAT
      concentration, dermatitis developed within a few days (1-7). The strength of the
      initial and the confirmatory patch test result, respectively, and the outcome of
      the ROAT were positively associated. Of the 24 patients with a use and
      confirmatory patch test, 15 reacted to 0.1% MDBGN, 16 to 0.2%, 17 to 0.3% and 22
      to 0.5%. With the patch test concentration of 0.5%, the number of ROAT-negative
      patients but patch-test-positive patients increases considerably, particularly
      due to + reactions. A maximum sensitivity of 94% (95% CI = 70-100%) is reached
      with a patch test concentration of 0.2%, and is not further improved by
      increasing the concentration. However, the specificity decreases dramatically
      from 88 (95% CI = 47-100%) with 0.2% to a mere 12.5% (95% CI = 0-53%) with 0.5%.
      It can be concluded (a) that for MDBGN 0.2% is very likely the best patch test
      concentration and (b) that 50 p.p.m. in a leave-on product can elicit contact
      dermatitis in sensitized persons. We were, therefore, unable to find a safe,
      still microbicidal, concentration for leave-on products. By contrast, with other
      contact allergens, dose-response use tests may be able to identify a non
      eliciting concentration, which could give valuable clues to a non-inducing (i.e.,
      safe) concentration in products.

PMID- 15859993
TI  - Patch testing with a new fragrance mix detects additional patients sensitive to
      perfumes and missed by the current fragrance mix.
AB  - The currently used 8% fragrance mix (FM I) does not identify all patients with a
      positive history of adverse reactions to fragrances. A new FM II with 6
      frequently used chemicals was evaluated in 1701 consecutive patients patch tested
      in 6 dermatological centres in Europe. FM II was tested in 3 concentrations - 28%
      FM II contained 5% hydroxyisohexyl 3-cyclohexene carboxaldehyde (Lyral), 2%
      citral, 5% farnesol, 5% coumarin, 1% citronellol and 10%alpha-hexyl-cinnamic
      aldehyde; in 14% FM II, the single constituents' concentration was lowered to 50%
      and in 2.8% FM II to 10%. Each patient was classified regarding a history of
      adverse reactions to fragrances: certain, probable, questionable, none. Positive
      reactions to FM I occurred in 6.5% of the patients. Positive reactions to FM II
      were dose-dependent and increased from 1.3% (2.8% FM II), through 2.9% (14% FM
      II) to 4.1% (28% FM II). Reactions classified as doubtful or irritant varied
      considerably between the 6 centres, with a mean value of 7.2% for FM I and means
      ranging from 1.8% to 10.6% for FM II. 8.7% of the tested patients had a certain
      fragrance history. Of these, 25.2% were positive to FM I; reactivity to FM II was
      again dose-dependent and ranged from 8.1% to 17.6% in this subgroup. Comparing 2
      groups of history - certain and none - values for sensitivity and specificity
      were calculated: sensitivity: FM I, 25.2%; 2.8% FM II, 8.1%; 14% FM II, 13.5%;
      28% FM II, 17.6%; specificity: FM I, 96.5%; 2.8% FM II, 99.5%; 14% FM II, 98.8%;
      28% FM II, 98.1%. 31/70 patients (44.3%) positive to 28% FM II were negative to
      FM I, with 14% FM II this proportion being 16/50 (32%). In the group of patients
      with a certain history, a total of 7 patients were found reacting to FM II only.
      Conversely, in the group of patients without any fragrance history, there were
      significantly more positive reactions to FM I than to any concentration of FM II.
      In conclusion, the new FM II detects additional patients sensitive to fragrances
      missed by FM I; the number of false-positive reactions is lower with FM II than
      with FM I. Considering sensitivity, specificity and the frequency of doubtful
      reactions, the medium concentration, 14% FM II, seems to be the most appropriate
      diagnostic screening tool.

PMID- 15859994
TI  - Patch testing with a new fragrance mix - reactivity to the individual
      constituents and chemical detection in relevant cosmetic products.
AB  - A new fragrance mix (FM II), with 6 frequently used chemicals not present in the
      currently used fragrance mix (FM I), was evaluated in 6 dermatological centres in
      Europe, as previously reported. In this publication, test results with the
      individual constituents and after repeated open application test (ROAT) of FM II
      are described. Furthermore, cosmetic products which had caused a contact
      dermatitis in patients were analysed for the presence of the individual
      constituents. In 1701 patients, the individual constituents of the medium (14%)
      and the highest (28%) concentration of FM II were simultaneously applied with the
      new mix at 3 concentrations (break-down testing for the lowest concentration of
      FM II (2.8%) was performed only if the mix was positive). ROAT was performed with
      the concentration of the FM II which had produced a positive or doubtful (+ or
      ?+) patch test reaction. Patients' products were analysed for the 6 target
      compounds by gas chromatography-mass spectrometry (GC-MS). RESULTS: 50 patients
      (2.9%) showed a positive reaction to 14% FM II and 70 patients (4.1%) to 28% FM
      II. 24/50 (48%) produced a positive reaction to 1 or more of the individual
      constituents of 14% FM II and 38/70 (54.3%) to 28% FM II, respectively. If
      doubtful reactions to individual constituents are included, the break-down
      testing was positive in 74% and 70%, respectively. Patients with a positive
      reaction to 14% FM II showed a higher rate of reactions to the individual
      constituent of the 28% FM II: 36/50 (72%). Positive reactions to individual
      constituents in patients negative to FM II were exceedingly rare. If doubtful
      reactions are regarded as negative, the sensitivity, specificity, positive
      predictive value and negative predictive value for the medium concentration of FM
      II towards at least 1 individual constituent was 92.3% (exact 95% confidence
      interval 74.9-99.1%), 98.4% (97.7-99.0%), 48% (33.7-62.6%) and 99.9% (99.6
      "100.0%), respectively. For the high concentration, the figures were very
      similar. The frequency of positive reactions to the individual constituents in
      descending order was the same for both FM II concentrations: hydroxyisohexyl 3
      cyclohexene carboxaldehyde (Lyral) > citral > farnesol > citronellol > alpha
      hexyl-cinnamic aldehyde (AHCA). No unequivocally positive reaction to coumarin
      was observed. Lyral) was the dominant individual constituent, with positive
      reactions in 36% of patients reacting to 14% FM II and 37.1% to 28% FM II. 5/11
      patients developed a positive ROAT after a median of 7 days (range 2-10). The 5
      patients with a doubtful or negative reaction to 28% FM II were all ROAT negative
      except 1. There were 7 patients with a certain fragrance history and a positive
      reaction to either 28% or 14% FM II but a negative reaction to FM I. Analysis
      with GC-MS in a total of 24 products obtained from 12 patients showed at least 1
      5 individual constituents per product: Lyral (79.2%), citronellol (87.5%), AHCA
      (58.3%), citral (50%) and coumarin (50%). The patients were patch test positive
      to Lyral, citral and AHCA. In conclusion, patients with a certain fragrance
      history and a negative reaction to FM I can be identified by FM II. Testing with
      individual constituents is positive in about 50% of cases reacting to either 14%
      or 28% FM II.

PMID- 15859995
TI  - Allergic contact dermatitis to drometrizole trisiloxane in a sunscreen with
      concomitant sensitivities to other sun screens.

PMID- 15859996
TI  - Erythrodermia caused by allergy to codeine.

PMID- 15859997
TI  - Contact allergy to decyl glucoside.

PMID- 15859998
TI  - Cutaneous allergic reaction to heparins: subcutaneous but not intravenous
      provocation.

PMID- 15859999
TI  - Peri- and subungual burns caused by hydrofluoric acid.

PMID- 15860000
TI  - Jellyfish dermatitis caused by Porpita pacifica, a sign of global warming?

PMID- 15860001
TI  - Allergic contact dermatitis from triethanolamine polypeptide oleate condensate in
      eardrops and shampoo.

PMID- 15860002
TI  - Mud bath dermatitis due to cinnamon oil.
AB  - A case of long-lasting, extensive eczematous and bullous dermatitis affecting
      exposed areas (arms and legs), beginning within 24 hr after having a mud bath
      with cinnamon essential oil in a spa, in a 74-year-old woman, is reported. Patch
      tests with the GEIDC standard battery and the dental battery (including clove
      essence and eugenol), cinnamon essence and its components were carried out 5
      years later. Fragrance mix, cinnamon essence, eugenol, cinnamic alcohol and
      cinnamic aldehyde yielded a positive result. To our knowledge, this is the first
      case of cinnamon dermatitis after a mud bath.

PMID- 15860003
TI  - Diagnostic value of SLS test.

PMID- 15860005
TI  - Mutants in DEFECTIVE GLYCOSYLATION, an Arabidopsis homolog of an
      oligosaccharyltransferase complex subunit, show protein underglycosylation and
      defects in cell differentiation and growth.
AB  - A mutant called defective glycosylation1-1 (dgl1-1) was identified in Arabidopsis
      based on a growth defect of the dark-grown hypocotyl and an abnormal composition
      of the non-cellulosic cell wall polysaccharides. dgl1-1 is altered in a protein
      ortholog of human OST48 or yeast WBP1, an essential protein subunit of the
      oligosaccharyltransferase (OST) complex, which is responsible for the transfer in
      the ER of the N-linked glycan precursor onto Asn residues of candidate proteins.
      Consistent with the known function of the OST complex in eukaryotes, the dgl1-1
      mutation led to a reduced N-linked glycosylation of the ER-resident protein
      disulfide isomerase. A second more severe mutant (dgl1-2) was embryo-lethal.
      Microscopic analysis of dgl1-1 revealed developmental defects including reduced
      cell elongation and the collapse and differentiation defects of cells in the
      central cylinder. These defects were accompanied by changes in the non-cellulosic
      polysaccharide composition, including the accumulation of ectopic callose.
      Interestingly, in contrast to other dwarf mutants that are altered in early steps
      of the N-glycan processing, dgl1-1 did not exhibit a cellulose deficiency.
      Together, these results confirm the role of DGL1 in N-linked glycosylation, cell
      growth and differentiation in plants.

PMID- 15860006
TI  - Alloplasmic effects on mitochondrial transcriptional activity and RNA turnover
      result in accumulated transcripts of Arabidopsis orfs in cytoplasmic male-sterile
      Brassica napus.
AB  - Mitochondrial transcription was investigated in a cytoplasmic male-sterile (CMS)
      Brassica napus line with rearranged mitochondrial (mt) DNA mostly inherited from
      Arabidopsis thaliana. The transcript patterns were compared with the
      corresponding male-fertile progenitors, B. napus and A. thaliana, and a fertility
      restored line. Transcriptional activities, gene stoichiometry and transcript
      steady-state levels were analysed for all protein and rRNA coding genes and for
      several orfs present in the A. thaliana mitochondrial genome. The transcriptional
      activities were highly variable when comparing the parental species, while the
      CMS and restored lines displayed similar activities. For several ribosomal
      protein genes transcriptional activity was reduced while it was increased for
      orf139 in comparison with the parental species. The differences in
      transcriptional activity observed could be related to differences in relative
      promoter strength, as gene stoichiometry between lines was very limited.
      Transcript steady-state levels were more homogenous than the transcriptional
      activities demonstrating RNA turnover as a compensating mechanism. In the CMS
      line higher transcript abundance and novel transcript patterns in comparison with
      the parental lines were found for several genes. Of those, the transcripts for
      orf139, orf240a and orf294 were less abundant in the fertility-restored line.
      These putative CMS-associated transcripts were mapped by cRT-PCR. In conclusion
      we show that (mt) DNA from A. thaliana was non-correctly transcribed and
      processed/degraded in the B. napus nuclear background. Furthermore, the
      introgressed nuclear A. thaliana DNA in the fertility-restored line contributes
      to a more rapid degradation of transcripts accumulated from A. thaliana derived
      orfs in the CMS line.

PMID- 15860007
TI  - Molecular cloning, characterization, and downregulation of an acyltransferase
      that catalyzes the malonylation of flavonoid and naphthol glucosides in tobacco
      cells.
AB  - Tobacco cells (Nicotiana tabacum L. Bright Yellow T-13) exposed to harmful
      naphthols accumulate them as glucosylated and further modified compounds [Taguchi
      et al. (2003a) Plant Sci. 164, 231-240]. In this study, we identified the
      accumulated compounds to be 6'-O-malonylated glucosides of naphthols. Cells
      treated with various phenolic compounds accumulated the flavonoids mainly as
      malonylglucosides. To clarify the function of this malonylation in tobacco, we
      isolated the cDNA encoding a malonyltransferase (NtMaT1) from a cDNA library
      derived from tobacco cells. The heterologous expression of the gene in
      Escherichia coli revealed that the recombinant enzyme had malonyltransferase
      activity against several phenolic glucosides such as flavonoid 7-O-glucosides,
      flavonoid 3-O-glucosides and naphthol glucosides. The substrate preference of the
      enzyme was similar to that of the tobacco cell extract. Malonylation activity in
      the transgenic cells markedly decreased with the suppression of the expression of
      NtMaT1 mRNA in tobacco BY-2 cells by RNA interference. The compounds administered
      to the transgenic cells were accumulated in the cells as glucosides or other
      modified compounds in place of malonylglucosides. These results show that NtMaT1
      is the main catalyst of malonylation on glucosides of xenobiotic flavonoids and
      naphthols in tobacco plants.

PMID- 15860008
TI  - Kinase partner protein interacts with the LePRK1 and LePRK2 receptor kinases and
      plays a role in polarized pollen tube growth.
AB  - The pollen-specific receptor kinases LePRK1 and LePRK2 have localization and
      expression profiles that strongly suggest they play roles in pollen germination
      and tube growth. To identify downstream components of LePRK signaling, we used
      their cytoplasmic domains (CDs) as baits in yeast two-hybrid screens of a tomato
      pollen cDNA library. A pollen-specific protein we named kinase partner protein
      (KPP) interacted with the CDs of both LePRK1 and LePRK2 in yeast and in an in
      vitro pull-down assay, and with LePRK2 in a co-immunoprecipitation assay. KPP is
      a peripheral membrane protein and is phosphorylated in pollen. Pollen tubes over
      expressing KPP developed balloon-like tips with abnormal cytoplasmic streaming
      and F-actin arrangements and plants over-expressing KPP exhibited impaired
      transmission of the transgene through the male. KPP-like genes are found only in
      plants; the 14 family members in Arabidopsis thaliana exhibit diverse expression
      patterns and potentially play roles in signaling pathways in other tissues.

PMID- 15860009
TI  - The Calvin cycle in cyanobacteria is regulated by CP12 via the NAD(H)/NADP(H)
      ratio under light/dark conditions.
AB  - In Synechococcus PCC7942 cells grown in the dark, the concentrations of NAD(H)
      and NADP(H) were 128+/-2.5 and 483+/-4.0 microm, respectively, while those in the
      cells under light conditions were 100+/-5.0 and 649+/-7.0 microm, respectively.
      Analysis of gel filtration indicated that the change of the ratio of NADP(H) to
      NAD(H) in cyanobacterial cells under light/dark conditions controls the
      reversible dissociation of the PRK/CP12/GAPDH complex (approximately 520 kDa)
      consisting of phosphoribulokinase (PRK), CP12, and glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH). S. 7942 CP12 lacked the two Cys residues essential for
      formation of the N-terminal peptide loop in the CP12 of higher plants, but the N
      terminal region of S. 7942 CP12 had the ability to be associated with PRK. The
      growth of mutant cells in which the CP12 gene was disrupted by a kanamycin
      resistance cartridge gene was almost the same as that of wild-type cells under
      continuous light conditions. However, under the light/dark cycle (12 h/12 h), the
      growth of CP12-disrupted mutant cells was significantly inhibited compared with
      that of wild-type cells. The mutant cells showed a decreased rate of O2
      consumption and an increased level of ribulose 1,5-bisphosphate compared with
      wild-type cells in the dark. These data suggest that under light and dark
      conditions, the oligomerization of CP12 with PRK and GAPDH regulates the
      activities of both enzymes and thus the carbon flow from the Calvin cycle to the
      oxidative pentose phosphate cycle.

PMID- 15860010
TI  - Point mutations in Arabidopsis Cullin1 reveal its essential role in jasmonate
      response.
AB  - The SKP1-Cullin/Cdc53-F-box protein ubiquitin ligases (SCF) target many important
      regulatory proteins for degradation and play vital roles in diverse cellular
      processes. In Arabidopsis there are 11 Cullin members (AtCUL). AtCUL1 was
      demonstrated to assemble into SCF complexes containing COI1, an F-box protein
      required for response to jasmonates (JA) that regulate plant fertility and
      defense responses. It is not clear whether other Cullins also associate with COI1
      to form SCF complexes, thus, it is unknown whether AtCUL1, or another Cullin that
      assembles into SCF(COI1) (even perhaps two or more functionally redundant
      Cullins), plays a major role in JA signaling. We present genetic and
      physiological data to directly demonstrate that AtCUL1 is necessary for normal JA
      responses. The homozygous AtCUL1 mutants axr6-1 and axr6-2, the heterozygous
      mutants axr6/AXR6, and transgenic plants expressing mutant AtCUL1 proteins
      containing a single amino acid substitution from phenylalanine-111 to valine, all
      exhibit reduced responses to JA. We also demonstrate that ax6 enhances the effect
      of coi1 on JA responses, implying a genetic interaction between COI1 and AtCUL1
      in JA signaling. Furthermore, we show that the point mutations in AtCUL1 affect
      the assembly of COI1 into SCF, thus attenuating SCF(COI1) formation.

PMID- 15860011
TI  - AtXTH27 plays an essential role in cell wall modification during the development
      of tracheary elements.
AB  - Xyloglucan endotransglucosylases/hydrolases (XTHs) are a class of enzymes capable
      of catalyzing the molecular grafting between xyloglucans and/or the endotype
      hydrolysis of a xyloglucan molecule. They are encoded by 33 genes in Arabidopsis.
      Whereas recent studies have revealed temporally and spatially specific expression
      profiles for individual members of this family in plants, their biological roles
      are still to be clarified. To identify the role of each member of this gene
      family, we examined phenotypes of mutants in which each of the Arabidopsis XTH
      genes was disrupted. This was undertaken using a reverse genetic approach, and
      disclosed two loss-of-function mutants for the AtXTH27 gene, xth27-1 and xth27-2.
      These exhibited short-shaped tracheary elements in tertiary veins, and reduced
      the number of tertiary veins in the first leaf. In mature rosette leaves of the
      mutant, yellow lesion-mimic spots were also observed. Upon genetic
      complementation by introducing the wild-type XTH27 gene into xth27-1 mutant
      plants, the number of tertiary veins was restored, and the lesions disappeared
      completely. Extensive expression of the pXTH27::GUS fusion gene was observed in
      immature tracheary elements in the rosette leaves. The highest level of AtXTH27
      mRNA expression in the rosette leaves was observed during leaf expansion, when
      the tracheary elements were elongating. These findings indicate that AtXTH27
      plays an essential role during the generation of tracheary elements in the
      rosette leaves of Arabidopsis.

PMID- 15860012
TI  - AtATG18a is required for the formation of autophagosomes during nutrient stress
      and senescence in Arabidopsis thaliana.
AB  - Vacuolar autophagy is a major pathway by which eukaryotic cells degrade
      macromolecules, either to remove damaged or unnecessary proteins, or to produce
      respiratory substrates and raw materials to survive periods of nutrient
      deficiency. During autophagy, a double membrane forms around cytoplasmic
      components to generate an autophagosome, which is transported to the vacuole. The
      outer membrane fuses with the vacuole or lysosome, and the inner membrane and its
      contents are degraded by vacuolar or lysosomal hydrolases. We have identified a
      small gene family in Arabidopsis thaliana, members of which show sequence
      similarity to the yeast autophagy gene ATG18. Members of the AtATG18 gene family
      are differentially expressed in response to different growth conditions, and one
      member of this family, AtATG18a, is induced both during sucrose and nitrogen
      starvation and during senescence. RNA interference was used to generate
      transgenic lines with reduced AtATG18a expression. These lines show
      hypersensitivity to sucrose and nitrogen starvation and premature senescence,
      both during natural senescence of leaves and in a detached leaf assay. Staining
      with the autophagosome-specific fluorescent dye monodansylcadaverine revealed
      that, unlike wild-type plants, AtATG18a RNA interference plants are unable to
      produce autophagosomes in response to starvation or senescence conditions. We
      conclude that the AtATG18a protein is likely to be required for autophagosome
      formation in Arabidopsis.

PMID- 15860013
TI  - Identification of a novel family of 70 kDa microtubule-associated proteins in
      Arabidopsis cells.
AB  - Most plant microtubule-associated proteins (MAPs) have homologues across the
      phylogenetic spectrum. To find potential plant-specific MAPs that will have
      evaded bioinformatic searches we devised a low stringency method for isolating
      proteins from an Arabidopsis cell suspension on endogenous taxol-microtubules. By
      tryptic peptide mass fingerprinting we identified 55 proteins that were enriched
      on taxol-microtubules. Amongst a range of known MAPs, such as kinesins, MAP65
      isoforms and MOR1, we detected 'unknown' 70 kDa proteins that belong to a family
      of five closely related Arabidopsis proteins having no known homologues amongst
      non-plant organisms. To verify that AtMAP70-1 associates with microtubules in
      vivo, it was expressed as a GFP fusion. This confirmed that the protein decorates
      all four microtubule arrays in both transiently infected Arabidopsis and stably
      transformed tobacco BY-2 suspension cells. Microtubule-directed drugs perturbed
      the localization of AtMAP70-1 but cytochalasin D did not. AtMAP70-1 contains four
      predicted coiled-coil domains and truncation studies identified a central domain
      that targets the fusion protein to microtubules in vivo. This study therefore
      introduces a novel family of plant-specific proteins that interact with
      microtubules.

PMID- 15860014
TI  - Functional importance of the family 1 glucosyltransferase UGT72B1 in the
      metabolism of xenobiotics in Arabidopsis thaliana.
AB  - The Arabidopsis type 1 UDP-glucose-dependent glucosyltransferase UGT72B1 is
      highly active in conjugating the persistent pollutants 3,4-dichloroaniline (DCA)
      and 2,4,5-trichlorophenol (TCP). To determine its importance in detoxifying
      xenobiotics in planta, mutant plants where the respective gene has been disrupted
      by T-DNA insertion have been characterized. Extracts from the knockout ugt72B1
      plants showed radically reduced conjugating activity towards DCA and TCP and the
      absence of immunodetectable UGT72B1 protein. In contrast, activities towards
      phenolic natural products were unaffected. When aseptic root cultures were fed
      [14C]-DCA, compared with wild types, the ugt72B1 plants showed a reduced rate of
      uptake of the xenobiotic and very little metabolism to soluble DCA-glucose or
      associated polar conjugates. Instead, the knockouts accumulated non-extractable
      radioactive residues, most probably associated with lignification. When the
      feeding studies were carried out with [14C]-TCP, rates and routes of metabolism
      were identical in the wild type and knockouts, with TCP-glucoside a major product
      in both cases. Similar differential effects on the metabolism of DCA and TCP were
      obtained in whole plant studies with wild type and ugt72B1 mutants, demonstrating
      that while UGT72B1 had a central role in metabolizing chloroanilines in
      Arabidopsis, additional UGTs could compensate for the conjugation of TCP in the
      knockout. TCP was equally toxic to wild type and ugt72B1 plants, while
      surprisingly, the knockouts were less sensitive to DCA. From this it was
      concluded that the glucosylation of DCA may not be as effective in xenobiotic
      detoxification as bound-residue formation.

PMID- 15860015
TI  - Comparative transcriptome analysis reveals significant differences in gene
      expression and signalling pathways between developmental and dark/starvation
      induced senescence in Arabidopsis.
AB  - An analysis of changes in global gene expression patterns during developmental
      leaf senescence in Arabidopsis has identified more than 800 genes that show a
      reproducible increase in transcript abundance. This extensive change illustrates
      the dramatic alterations in cell metabolism that underpin the developmental
      transition from a photosynthetically active leaf to a senescing organ which
      functions as a source of mobilizable nutrients. Comparison of changes in gene
      expression patterns during natural leaf senescence with those identified, when
      senescence is artificially induced in leaves induced to senesce by darkness or
      during sucrose starvation-induced senescence in cell suspension cultures, has
      shown not only similarities but also considerable differences. The data suggest
      that alternative pathways for essential metabolic processes such as nitrogen
      mobilization are used in different senescent systems. Gene expression patterns in
      the senescent cell suspension cultures are more similar to those for dark-induced
      senescence and this may be a consequence of sugar starvation in both tissues.
      Gene expression analysis in senescing leaves of plant lines defective in
      signalling pathways involving salicylic acid (SA), jasmonic acid (JA) and
      ethylene has shown that these three pathways are all required for expression of
      many genes during developmental senescence. The JA/ethylene pathways also appear
      to operate in regulating gene expression in dark-induced and cell suspension
      senescence whereas the SA pathway is not involved. The importance of the SA
      pathway in the senescence process is illustrated by the discovery that
      developmental leaf senescence, but not dark-induced senescence, is delayed in
      plants defective in the SA pathway.

PMID- 15860016
TI  - Arabidopsis mutants deregulated in RCI2A expression reveal new signaling pathways
      in abiotic stress responses.
AB  - To uncover new pathways involved in low-temperature signal transduction, we
      screened for mutants altered in cold-induced expression of RCI2A, an Arabidopsis
      gene that is not a member of the CBF/DREB1 regulon and is induced not only by low
      temperature but also by abscisic acid (ABA), dehydration (DH) and NaCl. This was
      accomplished by generating a line of Arabidopsis carrying a transgene consisting
      of the RCI2A promoter fused to the firefly luciferase coding sequence. A number
      of mutants showing low or high RCI2A expression in response to low temperature
      were identified. These mutants also displayed deregulated RCI2A expression in
      response to ABA, DH or NaCl. Interestingly, however, they were not altered in
      stress-induced expression of RD29A, a CBF/DREB1-target gene, suggesting that the
      mutations affect signaling intermediates of CBF/DREB1-independent regulatory
      pathways. Several mutants showed alterations in their tolerance to freezing, DH
      or salt stress, as well as in their ABA sensitivity, which indicates that the
      signaling intermediates defined by the corresponding mutations play an important
      role in Arabidopsis tolerance to abiotic stresses. Based on the mutants
      identified, we discuss the involvement of CBF/DREB1-independent pathways in
      modulating stress signaling.

PMID- 15860017
TI  - Visualization of autophagy in Arabidopsis using the fluorescent dye
      monodansylcadaverine and a GFP-AtATG8e fusion protein.
AB  - Autophagy is a process that is thought to occur in all eukaryotes in which cells
      recycle cytoplasmic contents when subjected to environmental stress conditions or
      during certain stages of development. Upon induction of autophagy, double
      membrane-bound structures called autophagosomes engulf portions of the cytoplasm
      and transfer them to the vacuole or lysosome for degradation. In this study, we
      have characterized two potential markers for autophagy in plants, the fluorescent
      dye monodansylcadaverine (MDC) and a green fluorescent protein (GFP)-AtATG8e
      fusion protein, and propose that they both label autophagosomes in Arabidopsis.
      Both markers label the same small, apparently membrane-bound structures found in
      cells under conditions that are known to induce autophagy such as starvation and
      senescence. They are usually seen in the cytoplasm, but occasionally can be
      observed within the vacuole, consistent with a function in the transfer of
      cytoplasmic material into the vacuole for degradation. MDC-staining and the GFP
      AtATG8e fusion protein can now be used as very effective tools to complement
      biochemical and genetic approaches to the study of autophagy in plant systems.

PMID- 15860018
TI  - Cortical release signs in psychiatry.
AB  - OBJECTIVE: To review the role of cortical release signs (CRS) in neuropsychiatry.
      METHOD: A thorough literature review was conducted using Medline and Psychlit
      databases, and other relevant references available to the authors. RESULTS: A
      number of neurological abnormalities are reported at elevated rates in
      neuropsychiatric conditions. CRS are a group of primitive reflexes that are
      present in the neonate but become inhibited as the infant central nervous system
      (CNS) develops, only to later re-emerge in the context of CNS disease. The
      clinical elicitation and interpretation of each CRS is described with reference
      to its neurobiology. The prevalence of CRS in schizophrenia, affective disorder,
      obsessive-compulsive disorder, Alzheimer's disease, vascular dementia,
      frontotemporal dementia and other neuropsychiatric illness allows for their use
      in the clinical management of these patients, including diagnostic assessment,
      treatment monitoring and prognosis. CONCLUSIONS: A number of issues complicate
      their interpretation in neuropsychiatric illness, including the apparent high
      base rate of some CRS in non-clinical populations, their increasing prevalence
      with age, lack of specificity and uncertainty over what constitutes an 'abnormal'
      response. In some circumstances, CRS may assist in diagnostic differentiation and
      illness staging.

PMID- 15860019
TI  - Application of risk assessment for violence methods to general adult psychiatry:
      a selective literature review.
AB  - OBJECTIVE: General adult psychiatrists are required to assess risk of violence as
      frequently as forensic psychiatrists. Yet most of the literature on risk
      assessment has originated from forensic settings, has been written by forensic
      psychiatrists, is applicable to forensic patients but may not apply to general
      psychiatric settings. Because the patient population and the nature of risk
      assessed may differ between the two settings, there is a need to consider the
      relevance of systems of assessment of risk of violence specific to the context of
      general adult psychiatry. METHODS: We searched the literature on the way risk has
      been conceptualized in different disciplines using Medline database from 1993 to
      2003. Keywords used were violence and risk management and risk assessment.
      Additional papers were identified from cross-references and personal knowledge of
      authors. RESULTS: Seven hundred and nine key papers were identified. We
      identified three common key concepts that define risk: Uncertainty, weighing up
      the likelihood of different outcomes arising and, the possibility of benefits as
      well as harm due to risk assessment. The impact of safety culture - the
      collection of beliefs, norms, attitudes, roles and practices while making daily
      activities and management decisions - on psychiatric thinking is examined. We
      review the two main methods of risk assessment from forensic psychiatric
      literature (actuarial and clinical) with a view to examine their utility in
      general adult psychiatric context. CONCLUSIONS: In order to develop a system of
      risk assessment relevant to general adult psychiatry, we note the benefits of
      shifting from risk prediction to assessment, management and reduction of risk,
      the need to merge actuarial and clinical approaches, communication of risk and
      finally the need to involve patients in the process of risk assessment.

PMID- 15860020
TI  - Antipsychotic treatment in obsessive-compulsive disorder: a literature review.
AB  - OBJECTIVE: To review the role of antipsychotic medications in the treatment of
      obsessive-compulsive disorder (OCD); to explore current hypothesized
      conceptualizations of their mechanism of action; to highlight evolving interest
      in the validation of meaningful OCD subtypes within a heterogeneous spectrum of
      OCD, based on treatment response and other psychobiological variables. METHOD: A
      computerized literature search (MEDLINE: 1966 to December 2003, EMBASE: 1982 to
      December 2003) was used to locate relevant literature, using the terms obsessive
      compulsive, antipsychotic and subtypes, with no restrictions imposed on searches.
      RESULTS: Earlier studies of augmentation of serotonergic antidepressants (SRIs)
      with typical antipsychotics including haloperidol and pimozide in OCD
      demonstrated favourable responses, also highlighting patient subgroups with
      robust treatment response. Studies examining augmentation with atypical agents
      are emerging. SRI-resistant OCD patients are likely to benefit from augmentation
      with atypical antipsychotics in around 50% of cases. CONCLUSIONS: While there is
      little role for antipsychotic monotherapy in OCD, there is growing evidence in
      support of adjunctive antipsychotics in OCD refractory to serotonin-reuptake
      inhibitors (SRIs). Further controlled trials are warranted. Particular subgroups
      of OCD patients, notably those with comorbid tic disorder and those with
      schizotypal personality disorder, have been shown to respond more robustly to
      augmentation strategies in some trials of both typical and atypical
      antipsychotics. Dopaminergic mediation with or without a moderating effect on
      serotonergic systems is likely to be important in the pharmacodynamic mechanisms
      of action of antipsychotic-SRI combinations in OCD.

PMID- 15860021
TI  - The validity of the DSM-IV subtypes of attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: To examine the validity of the three subtypes of ADHD defined by DSM
      IV. METHOD: Studies published in English were identified through searches of
      literature databases. RESULTS: Estimates of the prevalence of ADHD have increased
      as a result of the introduction of DSM-IV criteria. Factor analytical and genetic
      studies provide some support for the validity of the distinction between the
      three subtypes. However, diagnosis of the combined subtype seems more reliable
      than the other two subtypes, although reliability is largely unknown for the
      latter. The hyperactive-impulsive subtype, the least common, differs from the
      other two subtypes in age distribution, association with other factors and
      neuropsychological parameters. Almost all treatment trials are based on
      participants with the combined type. CONCLUSION: Data supporting the validity of
      the inattentive and hyperactive-impulsive subtypes of ADHD a decade after the
      publication of DSM-IV are still scarce. Given that inattention is the
      hypothesized core ADHD symptom, it remains to be demonstrated that hyperactive
      impulsive children who are not inattentive have the same condition. One of the
      main research deficits refers to data on treatment of the inattentive and
      hyperactive-impulsive subtypes.

PMID- 15860022
TI  - What is a clinically important level of improvement in symptoms of attention
      deficit/hyperactivity disorder?
AB  - OBJECTIVE: To compare the desired and actual reduction in scores on a parent
      reported behaviour rating scale in a naturalistic sample of children and
      adolescents who had been treated with psychostimulant medication, referenced to
      global ratings of treatment benefit. METHOD: Forty-five parents reporting poor
      global response to psychostimulant treatment, 44 reporting moderate response, and
      49 reporting a high response retrospectively completed Conners rating scales
      describing their child prior to treatment, the child currently, and how the
      parent hoped the child would be following treatment. RESULTS: Percentage actual
      improvement in behaviour rating scales from baseline ranged from around 25% for
      the poor responders to above 50% for the high responders. Desired improvement was
      above 50%, with no significant difference between the groups on level of
      expectation. CONCLUSIONS: Percentage cut points used to indicate clinical
      improvement reported in previous controlled trials of psychostimulant medication
      are probably too low, and could lead to an overestimate of treatment effect.
      Expectation of treatment benefit is unlikely to contribute to variation in
      treatment response.

PMID- 15860023
TI  - Characteristics of internalizing and externalizing disorders in medication-naive,
      clinically referred children with attention deficit hyperactivity disorder,
      combined type and dysthymic disorder.
AB  - OBJECTIVE: Internalizing and externalizing disorders are frequently comorbid with
      attention deficit hyperactivity disorder, combined type (ADHD-CT) and dysthymic
      disorder (DD) in referred primary school-age children, yet there has been
      relatively little systematic research of the nature of these comorbid disorders.
      We describe the characteristics of parent- and child-reported internalizing and
      externalizing disorders in primary school-age children with ADHD-CT and DD.
      METHOD: A cross-sectional study of 45 clinically referred medication naive
      children with ADHD-CT and DD, examining parent and child reports of internalizing
      and externalizing disorders, defined categorically and dimensionally. RESULTS:
      Generalized anxiety disorder and separation anxiety disorder were increased in
      the DD groups, whether ADHD-CT was present or not. Major depressive disorder was
      increased in the ADHD-CT and DD group compared to the ADHD-CT alone and the DD
      alone groups. Conduct disorder was increased in the ADHD-CT alone group compared
      to the DD with and without ADHD-CT groups. Verbal and fullscale IQ were increased
      in the DD groups, whether ADHD-CT was present or not, compared to the ADHD-CT
      alone group. CONCLUSIONS: There is emerging evidence that DD and anxiety may
      represent a different phenotypic expression of a common underlying aetiological
      process, while the co-occurrence of ADHD-CT and anxiety disorders remains
      unclear. Only the ADHD-CT and DD group is significantly associated with major
      depressive disorder, which suggests an additive effect. In contrast, conduct
      disorder and decreased verbal and fullscale IQ are only associated with the ADHD
      CT group, which may suggest a protective effect of DD when comorbid with ADHD-CT.
      From a research perspective, it is important to confirm these found associations
      in larger samples derived from epidemiological populations.

PMID- 15860024
TI  - Similarities and differences between aggressive and delinquent children and
      adolescents in a national sample.
AB  - OBJECTIVE: To examine differences in the correlates, comorbidity and use of
      services between aggressive and delinquent children and adolescents. METHOD: An
      Australian representative sample (n = 4083) of parents of children and
      adolescents were administered a psychiatric diagnostic interview, the Child
      Behaviour Checklist, and other instruments to measure service use. The
      characteristics of children with high scores (top 5%) in the aggressive and
      delinquent syndromes or both were then examined. RESULTS: The proportion of
      aggressive children decreased with increasing age while that of delinquents
      increased. The aggressive group was specifically associated with the impulsive
      hyperactive subtype of attention deficit hyperactivity disorder (ADHD) (OR =
      12.63; 95% CI = 5.97-26.74). Comorbidity between ADHD, aggression and delinquency
      was less frequent among adolescents than in children, with the exception of the
      inattentive subtype in which comorbidity was higher. Both aggressive and
      delinquent groups had a considerable overlap with conduct disorder. Aggressive
      and delinquent youths used services more often, but parents perceived aggressive
      children as more in need of help than delinquent ones. Living in a sole parent
      family was specifically associated with the delinquent group (OR = 3.34; 95% CI =
      2.25-4.96). CONCLUSIONS: The results suggest that these empirically derived
      syndromes while sharing many features also differ in important ways, highlighting
      the need for further convergence between categorical and dimensional
      classifications. Their differential association with the subtypes of ADHD
      requires further examination and may help to understand the relationship between
      ADHD and conduct problems. The importance of aggressive behaviour in children
      should not be underestimated since it is associated with significant
      psychopathology, parental distress and use of services.

PMID- 15860025
TI  - Dyssomnia in children diagnosed with attention deficit hyperactivity disorder: a
      critical review.
AB  - OBJECTIVE: Studies prior to 1999 reported prevalent sleep disturbances in
      children diagnosed with attention deficit hyperactivity disorder (ADHD). However,
      these reports were largely inconclusive and inconsistent in their findings, hence
      the current review based on studies published thereafter. METHOD: An online
      research of the National Library of Medicine and the Cochrane Library was
      conducted using the terms 'attention deficit hyperactivity disorder', 'sleep',
      'human', and 'English language'. RESULTS: Sixteen articles met the search
      criteria with 10 reporting objective measures of sleep characteristics (i.e.
      polysomnography, actigraphy, and/or video recording). These studies confirm an
      increase of rapid eye movement (REM) sleep latency and a proportional decrease of
      REM sleep in children diagnosed with ADHD. Stimulant treatment appears to have
      little effect on sleep quality while parent's reports of poor sleep in their ADHD
      diagnosed offspring was largely inconsistent with the objective measures.
      CONCLUSIONS: The review demonstrated a link between disturbances in sleep
      architecture and ADHD. Whether this is of an intrinsic or extrinsic cause remains
      debateable, as both behavioural (parental reporting) and physiological (objective
      differences in sleep architecture) factors are indicated. The effect of stimulant
      medication on sleep also requires further research, as current evidence is
      limited by study design.

PMID- 15860026
TI  - Screening for autism in infants and preschool children with developmental delay.
AB  - OBJECTIVE: This study aimed to identify emotional and behavioural problems
      specific to young children with autism using the Developmental Behaviour
      Checklist (DBC-P) and thus evaluate the efficacy of this checklist as a screening
      tool for autism in children with developmental delay aged 18-48 months. METHOD:
      Subjects were 60 children with autism and developmental delay and 60 children
      with developmental delay without autism. RESULTS: Features were identified which
      differentiated the children with autism from those with developmental delay
      without autism. Analyses revealed that a 17-item version of the DBC-P performed
      well as a screening tool for autism, with an 'area under the curve' of 0.874,
      sensitivity of 0.8750, and specificity of 0.6909. CONCLUSIONS: The DBC-P offers a
      potential simple and inexpensive method of screening at risk populations of
      preschool children with developmental delay for autism, thus facilitating timely
      referral to scarce specialist autism diagnostic services.

PMID- 15860027
TI  - Factors associated with pathological dissociation in the general population.
AB  - OBJECTIVE: This study assessed the prevalence of pathological dissociation in the
      general population, and the relationship between pathological dissociation and
      sociodemographic and several psychiatric variables. METHOD: The stratified
      population sample consisted of 2001 subjects. The study questionnaires included
      the Dissociative Experiences Scale, the Dissociative Experiences Scale-Taxon, the
      Toronto Alexithymia Scale, the Beck Depression Inventory, and sociodemographic
      background. RESULTS: The prevalence of pathological dissociation (DES-T >/= 20)
      was 3.4% in the general population and did not differ significantly between
      genders. Men scored higher than women in the amnesia subscale, and women in the
      absorption and imaginative involvement subscale. The relationship between
      pathological dissociation, alexithymia, depression and suicidality was strong.
      The likelihood of pathological dissociation was nearly nine-fold higher among
      depressive subjects, more than seven-fold higher among alexithymic subjects, and
      more than four-fold higher among suicidal subjects than among the others.
      Frequent alcohol consumption also associated significantly with pathological
      dissociation. CONCLUSIONS: A significant relationship between pathological
      dissociation, depression, alexithymia, and suicidality was found in the general
      population. The importance of these factors should be examined in a prospective
      study design to determine causality.

PMID- 15860028
TI  - Prevalence of intellectual disability and comorbid mental illness in an
      Australian community sample.
AB  - OBJECTIVE: The aim of this study was to bring to light the high prevalence of
      Australians affected by intellectual disability and comorbid serious mental
      illnesses. Results from a broad scale study are used to explore the reasons for
      this regularly overlooked phenomenon. METHODS: This study was based on secondary
      analysis of data collected in the national 'Disability, Ageing and Carers Survey,
      1998'. The analysed data consisted of an Australian wide sample of 42 664
      individuals living at home or in cared accommodation. Classification of
      intellectual disability and comorbid psychosis, anxiety and depressive disorder
      was based on the International Statistical Classification of Diseases and Related
      Health Problems, 10th Revision (ICD-10). RESULTS: The prevalence of intellectual
      disability in the sampled population was 1.25%. Of these people 1.3% had a
      psychotic disorder, 8% had a depressive disorder and 14% had an anxiety disorder
      that had been present for at least 6 months and was of such severity that it too
      was disabling. CONCLUSIONS: Findings indicate that people with intellectual
      disability are at high risk of developing comorbid serious mental illness. Dual
      diagnosis is however, often overlooked due to difficulties associated with
      establishing a diagnosis of a mental disorder in people with an intellectual
      disability, a problem which is heightened when the individual's capacity to
      participate in a clinical assessment is limited.

PMID- 15860029
TI  - Mental disorders among Maori attending their general practitioner.
AB  - OBJECTIVE: This paper identifies rates of common mental disorders among Maori and
      non-Maori consulting a general practitioner (GP), and explores the association
      between ethnicity and social and material deprivation. METHOD: Survey of GPs and
      their patients. Participants were randomly selected GPs (n = 70), and their
      patients (n = 3414, of whom a subset of 786 form the basis of this paper). The
      main comparison is between self-identified ethnicity, mental disorder assessed by
      the Composite International Diagnostic Interview, and social and material
      deprivation measured by NZDep2001 (an area based measure), and an individualized
      index of deprivation. RESULTS: Rates of mental disorder among Maori general
      practice attenders were higher than among non-Maori. Overall, Maori women
      attenders were twice as likely as non-Maori women attenders to have a diagnosable
      mental disorder. The rates of anxiety, depressive and substance use disorders
      were all higher for Maori than for others attending GPs. Treatment for
      psychological problems was offered by the GP at similar rates to both Maori and
      non-Maori. Although there were differences between Maori and non-Maori in terms
      of social and material deprivation, higher rates of mental disorder among Maori
      attending GPs compared to non-Maori cannot be accounted for by these differences
      alone. CONCLUSIONS: These findings support the view that whilst social and
      material deprivation may play a role in the high rates of mental disorders among
      Maori general practice attenders, there are additional ethnicity-specific factors
      involved. Interventions to address Maori mental health (whether by reducing risk
      factors for mental disorder, by promoting disclosure, early recognition and
      intervention, or by ensuring access to acceptable and effective treatments) may
      need to explicitly take those factors into account.

PMID- 15860030
TI  - Mental disorder in the New South Wales prisoner population.
AB  - OBJECTIVES: To determine the prevalence of mental illness among prisoners in New
      South Wales (NSW), Australia. METHOD: Mental illness was examined in two NSW
      prisoner populations: (i) new receptions to the correctional system; and (ii)
      sentenced prisoners. Reception prisoners were screened at four male centres and
      one female centre in NSW. The sentenced population was randomly selected from 28
      correctional centres across the state. Reception prisoners were screened
      consecutively whenever possible while the sentenced group was randomly selected
      as part of the 2001 Inmate Health Survey. We adopted the same instrument,
      Composite International Diagnostic Interview - Auto (CIDI-A), for diagnosing
      mental illness as used in the Australian National Survey of Mental Health and
      Wellbeing. RESULTS: Overall, 43% of those screened had at least one of the
      following diagnoses: psychosis, anxiety disorder, or affective disorder.
      Reception prisoners suffered from mental illness to a greater extent than
      sentenced prisoners (46%vs. 38%). Women had higher levels of psychiatric
      morbidity than men (61%vs. 39%). Nine percent (9%) of all prisoners had
      experienced psychotic symptoms (due to any cause) in the prior 12 months. Twenty
      percent (20%) of all prisoners had suffered from at least one type of mood
      disorder and 36% had experienced an anxiety disorder. Posttraumatic stress
      disorder was the most common disorder, diagnosed in 26% of receptions and 21% of
      sentenced prisoners. CONCLUSIONS: These findings confirm that prisoners are a
      highly mentally disordered group compared with the general community. Given the
      high prevalence of mental illness identified by this study, it is essential that
      prison mental health services be adequately resourced to address the demand and,
      at minimum, ensure that mental health does not deteriorate during incarceration.

PMID- 15860031
TI  - Psychiatric out-patients seen once only in South Verona and Western Australia: a
      comparative case-register study.
AB  - OBJECTIVE: This study examined variables associated with having a once-only
      contact with the out-patient department of two community mental health services
      in Italy and Australia. METHOD: Two 8-year cohorts of patients, who had a new
      episode of care with out-patient psychiatric departments in South Verona and in
      Western Australia, were followed-up for 3 months after the first contact, to
      identify those patients who had no further contact with services. Potential
      determinants of once-only contact were analysed. RESULTS: Thirty percent of new
      episodes of care for persons who met the inclusion criteria of the study were
      once-only contacts with the service in South Verona. In Western Australia, the
      figure was 24%. Moreover, the proportion of once-only contact patients has
      increased over time in South Verona whereas, in Western Australia, it has
      remained stable. In Western Australia, once-only contact patients were younger
      whereas in South Verona they tended to be older. At both research sites, patients
      who had a once-only contact were more likely to be male and to have a less severe
      mental illness. CONCLUSIONS: The results of this study suggest that only clinical
      characteristics were significant determinants of this pattern of contact with
      services consistently at both sites: the less severe the patient's diagnosis, the
      more likely the patient is to have a once-only contact. This may well indicate
      good screening at the initial point of contact by both sets of mental health
      service providers. Prospective studies are necessary to clarify the problem of
      'once-only contact' and to organize a proper psychiatric care.

PMID- 15860032
TI  - Obfuscating clinical and political views on demoralization.

PMID- 15860033
TI  - Dissociative trance disorder associated with major depression and bereavement in
      a South African female adolescent.

PMID- 15860035
TI  - Publicity re past abuses of patients in mental hospitals.

PMID- 15860040
TI  - Waiving consent for emergency research.

PMID- 15860041
TI  - Vitamin D and calcium deficits predispose for multiple chronic diseases.
AB  - There is evidence from both observational studies and clinical trials that
      calcium malnutrition and hypovitaminosis D are predisposing conditions for
      various common chronic diseases. In addition to skeletal disorders, calcium and
      vitamin D deficits increase the risk of malignancies, particularly of colon,
      breast and prostate gland, of chronic inflammatory and autoimmune diseases (e.g.
      insulin-dependent diabetes mellitus, inflammatory bowel disease, multiple
      sclerosis), as well as of metabolic disorders (metabolic syndrome, hypertension).
      The aim of the present review was to provide improved understanding of the
      molecular and cellular processes by which deficits in calcium and vitamin D cause
      specific changes in cell and organ functions and thereby increase the risk for
      chronic diseases of different aetiology. 1,25-Dihydroxyvitamin D(3) and
      extracellular Ca(++) are both key regulators of proliferation, differentiation
      and function at the cellular level. However, the efficiency of vitamin D receptor
      mediated intracellular signalling is limited by the negative effects of
      hypovitaminosis D on extrarenal 25-hydroxyvitamin D-1alpha-hydroxylase activity
      and thus on the production of 1,25-dihydroxyvitamin D(3). Calcium malnutrition
      eventually causes a decrease in calcium concentration in extracellular fluid
      compartments, resulting in organ-specific modulation of calcium-sensing receptor
      activity. Hence, attenuation of signal transduction from the ligand-activated
      vitamin D receptor and calcium-sensing receptor seems to be the prime mechanism
      by which calcium and vitamin D insufficiencies cause perturbation of cellular
      functions in bone, kidney, intestine, mammary and prostate glands, endocrine
      pancreas, vascular endothelium, and, importantly, in the immune system. The wide
      range of diseases associated with deficits in calcium and vitamin D in
      combination with the high prevalence of these conditions represents a special
      challenge for preventive medicine.

PMID- 15860042
TI  - Oxidative stress and cardiovascular risk: the role of vascular NAD(P)H oxidase
      and its genetic variants.
AB  - Several risk factors for coronary artery disease (CAD) induce atherosclerosis
      through endothelial activation and dysfunction, and ample evidence now suggests
      that the balance between production and removal of reactive oxygen species (ROS) 
      a condition termed oxidative stress - is implicated in such processes. A main
      source of ROS in vascular cells is the reduced nicotinamide adenine
      dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase
      system. This is a membrane-associated enzyme, composed of five subunits,
      catalyzing the one-electron reduction of oxygen, using NADH or NADPH as the
      electron donor. One of the system subunits, termed p22-phox, has a polymorphic
      site on exon 4, associated with variable enzyme activity. This polymorphism is
      generated by a point mutation (C(242)T) producing a substitution of histidine
      with tyrosine at position 72, which affects one of the heme binding sites
      essential for the NAD(P)H enzyme activity. The consequent decrease of superoxide
      production thus characterizes a phenotype candidate for conferring to the carrier
      a reduced susceptibility to CAD. At present, however, the body of evidence from
      current literature is not yet sufficient to confirm or exclude the hypothesis
      that the C(242)T polymorphism protects from CAD. The functional effects of this
      polymorphism and the potential and its pathophysiological consequences also need
      further investigation.

PMID- 15860043
TI  - International multicentre trial protocol to assess the efficacy and safety of
      tenecteplase during cardiopulmonary resuscitation in patients with out-of
      hospital cardiac arrest: the Thrombolysis in Cardiac Arrest (TROICA) Study.
AB  - Prehospital cardiac arrest has been associated with a very poor prognosis. Acute
      myocardial infarction and massive pulmonary embolism are the underlying causes of
      out-of-hospital cardiac arrest in 50-70% of patients. Although fibrinolysis is an
      effective treatment strategy for both myocardial infarction and pulmonary
      embolism, clinical experience for this therapy performed during resuscitation has
      been limited owing to the anticipated risk of severe bleeding complications. The
      TROICA study is planned as one of the largest randomized, double-blind, placebo
      controlled trials to assess the efficacy and safety of prehospital thrombolytic
      therapy in cardiac arrest of presumed cardiac origin. Approximately 1000 patients
      with cardiac arrest will be randomized at approximately 60 international study
      centres to receive either a weight-adjusted dose of tenecteplase or placebo after
      the first dose of a vasopressor. Patients can be included if they are at least 18
      years, presenting with a witnessed cardiac arrest of presumed cardiac origin, and
      if either basic life support had started within 10 min of onset and had been
      performed up to 10 min or advanced life support is started within 10 min of onset
      of cardiac arrest. Primary endpoint of the study is the 30-day survival rate, and
      the coprimary endpoint is hospital admission. Secondary endpoints are the return
      of spontaneous circulation (ROSC), survival after 24 h, survival to hospital
      discharge, and neurological performance. Safety endpoints include major bleeding
      complications and symptomatic intracranial haemorrhage.

PMID- 15860044
TI  - Factors predicting the development of metabolic syndrome and type II diabetes
      against a background of hypertension.
AB  - BACKGROUND: The metabolic syndrome (MetS), predicting coronary heart disease
      (CHD), is a compound of risk factors including diabetes, obesity and
      hypertension. The relationship between the development of MetS, diabetes and CHD
      in patients with established hypertension is unclear. We hypothesized that
      patients with hypertension developing MetS are at increased risk of type II
      diabetes and CHD compared with patients who do not develop MetS. MATERIALS AND
      METHODS: We prospectively studied 284 patients (100 with existing/established
      MetS) with hypertension but without diabetes and CHD over 4 years. MetS and
      diabetes were diagnosed by the modified NCEP and ADA criteria, and CHD risk by
      the Framingham risk equation; all patients had annual fasting blood sampling.
      RESULTS: Over 4 years of follow up, 75 of the 184 patients (41%) initially free
      of MetS at baseline subsequently fulfilled the criteria for MetS. These patients
      (i.e. 'developing MetS') had higher baseline BMI, triglycerides and lower HDL
      cholesterol, with a higher calculated CHD risk (all P <or= 0.001) than those who
      did not develop MetS. The 4-year odds ratios of developing diabetes in the
      patients with established MetS (23%) and the patients developing MetS (13.3%) vs.
      the patients not developing MetS (3.7%, P < 0.001) were 7.8 (95% CI: 2.6-23.5)
      and 4.0 (95% CI: 1.2-13.4), respectively. CONCLUSIONS: Patients with hypertension
      developing MetS have an increased CHD risk and risk of developing type II
      diabetes even before fulfilling the criteria for MetS, and the former is
      comparable to patients with established MetS. These data suggest a high-risk
      phase not adequately identified by current diagnostic thresholds for MetS.

PMID- 15860045
TI  - Glomerular hyperfiltration in type 1 diabetes mellitus results from primary
      changes in proximal tubular sodium handling without changes in volume expansion.
AB  - BACKGROUND: Glomerular hyperfiltration plays a role in the pathophysiology of
      diabetic nephropathy. An increase in the glomerular filtration rate (GFR) could
      result from primary actions at the glomerular/vascular level or could be the
      consequence of a primary increase in proximal tubular sodium reabsorption
      resulting in systemic volume expansion. Recently it was hypothesized that an
      increase in sodium reabsorption may lead to glomerular hyperfiltration through
      the tubulo-glomerular feedback mechanism (tubular-hypothesis) without volume
      expansion. DESIGN: We have studied 54 normoalbuminuric patients with type 1
      diabetes. The GFR was measured by inulin clearance. Proximal and distal sodium
      reabsorption were calculated according to standard formulas using the free water
      clearance technique. Plasma volume, measured by the (125)I-albumin method, atrial
      natriuretic peptide (ANP) and the second messenger cyclic guanosine-3,5
      monophosphate (c-GMP) were used as markers of extracellular volume expansion.
      RESULTS: Glomerular hyperfiltration (GFR >or= 130 mL min(-1) 1.73 m(-2)) was
      present in 14 out of 55 patients with diabetes (25%). There were no differences
      in plasma volume between normo-(NF) and hyper-filtrating (HF) patients (2933 +/-
      423 in NF vs. 3026 +/- 562 mL in HF, NS). Also plasma ANP and c-GMP levels were
      not significantly different between the groups. The fractional proximal
      reabsorption of sodium was significantly increased in HF [fPRNa(+) (%) 90.1 +/-
      2.0 vs. 91.5 +/- 1.6, P = 0.02]. There were no differences in distal sodium
      reabsorption or distal sodium load (approximately macula densa concentration of
      NaCl) in both groups. CONCLUSIONS: Our data suggest that the primary event in
      diabetic glomerular hyperfiltration is an increase in proximal tubular sodium
      reabsorption. They do not support the hypothesis that systemic volume expansion
      or ANP mediate glomerular hyperfiltration in patients with normoalbuminuric type
      1 diabetes. As such, changes in tubular sodium handling most probably influence
      tubulo-glomerular feedback.

PMID- 15860046
TI  - Antithrombotic effect of a new nitric oxide donor (LA419) on experimental
      thrombogenesis.
AB  - BACKGROUND: The ability of nitrous compounds to donate nitric oxide (NO), an
      agent with vasodilating and inhibitory effects on platelet function, has been
      considered a useful pharmacologic strategy for cardiovascular complications. The
      purpose of this study was to investigate the effects of a new NO donor, LA419, on
      platelet interaction in an ex vivo model with human blood circulating through
      collagen-rich surfaces. MATERIALS AND METHODS: Platelet adhesive and cohesive
      function were analyzed by morphometric procedures after perfusion techniques.
      Treated blood was exposed to thrombogenic surfaces and platelet interactions were
      morphometrically evaluated. RESULTS: All the concentrations studied of LA419 (10
      microM, 20 microM and 100 microM) reduced overall platelet interaction with a
      collagen surface (27.19 +/- 4.72; 25.52 +/- 3.52; and 23.44 +/- 3.01, P < 0.05,
      respectively, vs. 32.31 +/- 1.61% in the control). The antithrombotic effect was
      confirmed by results in cross-sectional studies performed in arterial vessels
      exposed to circulating blood. Values of thrombus and covered surface at 20 microM
      LA419 were, respectively, 13.67 +/- 4.97% and 19.01 +/- 5.89%; respect to
      controls 34.80 +/- 5.29% and 37.93 +/- 5.34% (P < 0.05). Moreover, LA419 reduced
      significantly thrombus area (88.45 +/- 21.97 microm(2); P < 0.05) with respect to
      controls (168.45 +/- 21.97 microm(2)) and thrombus height, from an average of
      10.27 +/- 1.05 microm in nontreated blood to 7.16 +/- 0.6 microm in treated
      samples (P < 0.05). CONCLUSION: From the present data we can conclude that LA419
      possesses a strong antiplatelet action, as demonstrated by its ability to
      significantly inhibit the interaction of platelet with highly thrombogenic
      collagen surfaces.

PMID- 15860047
TI  - 22-ene-25-oxa-vitamin D: a new vitamin D analogue with profound immunosuppressive
      capacities.
AB  - BACKGROUND: The biologic role of 1,25-dihydroxyvitamin D(3), such as anti
      inflammatory functions, reduction of cytokine production by T cells and
      immunoglobulin production by B cells, is well established. However, its clinical
      use as an immunosuppressive agent is limited because of the hypercalcemic
      toxicity occurring after systemic application. The purpose of this study was to
      investigate the immunmodulatory effects of 22-ene-25-oxa-vitamin D (ZK156979), a
      novel low calcemic vitamin D analogue. MATERIALS AND METHODS: Human peripheral
      blood mononuclear cells (PBMCs) from healthy donors were isolated using the
      Ficoll Hypaque technique, cultured for 24 h and treated with different
      concentrations of ZK156979 ranging from 10(-5) to 10(-10) mol L(-1) compared with
      1,25-dihydroxyvitamin D(3)[10(-5)-10(-10) mol L(-1)] following
      phytohaemagglutinin (PHA) stimulation. Interferon gamma (IFNgamma), tumour
      necrosis factor alpha (TNFalpha), interleukin 1 beta (IL-1beta), interleukin 10
      (IL-10) and interleukin 4 (IL-4) secretion in supernatants were measured by
      ELISA. RESULTS: ZK156979 inhibited the PHA-induced Th1-response (IFNgamma and
      TNFalpha levels) and the macrophage-product IL-1beta in a concentration-dependent
      manner (10(-10)-10(-5) mol L(-1)) with the efficiency on cytokine expression
      compared with 1,25-dihydroxyvitamin D(3) being slightly reduced. In contrast,
      ZK156979 and 1,25-dihydroxyvitamin D(3) both affected the Th2 response, leading
      to significantly increased IL-10- and IL-4 secretion. CONCLUSIONS: ZK156979 is a
      member of novel vitamin D analogues revealing prominent immunomodulatory and
      suppressive characteristics with distinctive inhibition of Th1-cytokines whereas
      the Th2 compartment is augmented, thus providing a considerable therapeutic
      potential in T-cell -mediated diseases.

PMID- 15860048
TI  - Retraction of publication.

PMID- 15860049
TI  - Shared decision-making: the debate continues.

PMID- 15860050
TI  - The role of doctor's opinion in shared decision making: what does shared decision
      making really mean when considering invasive medical procedures?
AB  - OBJECTIVE: The goal of this study was to gain understanding about patients'
      perspectives on decision making in the context of invasive medical interventions
      and whether patients' decision-making preferences influenced the type of
      information they desired to be provided by physicians. DESIGN: Questionnaire
      study of consecutive patients in a university-based general medicine clinic.
      INTERVENTIONS: Patients were presented with a randomized list of three types of
      information that physicians could provide (risk, benefit and physician's opinion
      on whether they should undergo the procedure). Patients were asked whether they
      preferred patient-based, physician-based, or shared decision making and then were
      asked to select which one or combination of these three information types was
      most important to them in their own decision making. Patients were also asked to
      self-report on how many invasive procedures they had undergone in their own
      lives. PARTICIPANTS: A total of 202 consecutive patients (mean age = 65.1 years,
      SD = 12.3, range 28-88; mean education 13.3 years, SD 2.9, range 2-23). MAIN
      OUTCOME MEASURES: Patient reports. RESULTS: Of the 202 patients, two patients
      reported no decision-making preference. These two patients were excluded from the
      analysis. Of the 200 remaining patients, 62.5% (125/200) preferred shared,
      22.5%(45/200) preferred physician-based, and 15.5% (31/200) preferred patient
      based decision making. More than half of all subjects chose physician opinion as
      the most important type of information for decision making. Older patients (odds
      ratio 1.028; confidence interval 1.003-1.053) were more likely to have ranked the
      doctor's opinion as the most important in their decision making for invasive
      medical interventions. CONCLUSIONS: Although most patients want to share decision
      making with their physicians regarding invasive procedures, the majority of these
      patients report relying on the doctor's opinion on whether to undergo the
      procedure as the most important information in their own decision making.

PMID- 15860051
TI  - Exploring the decision-making preferences of people with colorectal cancer.
AB  - OBJECTIVES: To explore patient views on participation in treatment, physical care
      and psychological care decisions and factors that facilitate and hinder patients
      from making decisions. DESIGN: Qualitative study using semi-structured interviews
      with patients. SETTING AND PARTICIPANTS: Three NHS Trusts in the north-west of
      England. Theoretical sampling including 41 patients who had been treated for
      colorectal cancer. RESULTS: For patients, participation in the decision-making
      process was about being informed and feeling involved in the consultation
      process, whether patients actually made decisions or not. The perceived
      availability of treatment choices (surgery, radiotherapy, chemotherapy) was
      related to type of treatment. Factors that impacted on whether patients wanted to
      make decisions included a lack of information, a lack of medical knowledge and
      trust in medical expertise. Patients perceived that they could have a more
      participatory role in decisions related to physical and psychological care.
      CONCLUSION: This study has implications for health professionals aiming to
      implement policy guidelines that promote patient participation and shared
      partnerships. Patients in this study wanted to be well informed and involved in
      the consultation process but did not necessarily want to use the information they
      received to make decisions. The presentation of choices and preferences for
      participation may be context specific and it cannot be assumed that patients who
      do not want to make decisions about one aspect of their care and treatment do not
      want to make decisions about other aspects of their care and treatment.

PMID- 15860052
TI  - Treatment decision aids: conceptual issues and future directions.
AB  - BACKGROUND: In the last 10 years, there has been a major growth in the
      development of treatment decision aids. Multiple goals have been identified for
      these tools. However, the rationale for and meaning of these goals at the
      conceptual level, the mechanisms through which decision aids are intended to
      achieve these goals, and value assumptions underlying the design of aids and
      associated values clarification exercises have often not been made explicit.
      OBJECTIVE: In this paper, we present ideas to help inform the future development
      and evaluation of decision aids. RESULTS: We suggest, (i) that the
      appropriateness of using any decision aid be assessed within the context of the
      wider decision-making encounter within which it is embedded; (ii) that goal
      setting activities drive measurement activities and not the other way round;
      (iii) that the rationale for and meaning of goals at the conceptual level, and
      mechanisms through which they are intended to have an impact be clearly thought
      through and made explicit; (iv) that value assumptions underlying both decision
      aids and associated values clarification exercises be communicated to patients;
      (v) that taxonomies developed and used to classify various types of decision aids
      include a section on value assumptions underlying each tool; (vi) that further
      debate and discussion take place on the role of explicit values clarification
      exercises as a component of or adjunct to treatment decision aids and the
      feasibility of implementing valid measures. CONCLUSION: Further debate and
      discussion is needed on the above issues.

PMID- 15860053
TI  - Quality criteria for patient advice and liaison services: what do patients and
      the public want?
AB  - BACKGROUND: Every NHS trust and Primary Care Trust (PCT) in England now has a
      Patient Advice and Liaison Service (PALS) which provides an identifiable person
      to whom service users can turn if they have a problem or need information while
      using the NHS. This paper reports data from a 2-year qualitative study of London
      PALS. OBJECTIVE: To develop patient-centred criteria by which to assess PALS.
      DESIGN: Data were generated from qualitative interviews with 15 PALS service
      users and 15 members of local user/carer organizations, and from a workshop with
      representatives of 14 user/carer organizations (national and London-wide).
      Emergent findings were circulated to other user/carer organizations (n = 32) for
      critique and comment. RESULTS: Findings suggest that users and their
      representatives want PALS to: be responsive to the needs and wishes of
      individuals; be accessible to all sections of the community, including older
      people, ethnic minorities and groups with special needs; offer clear, accurate
      and comprehensive information about local health and other services; work with
      their NHS organization to create a more patient-centred service; collaborate
      effectively with other organizations; be adequately resourced. CONCLUSIONS: These
      criteria resemble the national standards for PALS compiled by the Department of
      Health, with the exception of the need for adequate resourcing. They also
      resemble previous work on users' and carers' criteria for service delivery.
      Interestingly, PALS' lack of independence was not a major concern, though clients
      do need access to independent advocacy when 'insider' trouble-shooting fails.
      Although an alternative to the adversarial approach of complaints is welcome,
      PALS, like complaints procedures, may be under-used by marginalized or
      demoralized service users.

PMID- 15860054
TI  - A survey and audit of the first 'Guides to Local Health Services' produced by
      Primary Care Trusts in England.
AB  - BACKGROUND: Providing more information for the public about the range and quality
      of health services is an important part of improving accountability, quality and
      public responsiveness. Most sources of information to date have failed to address
      the information needs of people about their local services. The launch in England
      in 2002 of a new publication, Guides to Local Health Services, was designed to
      address this deficiency. We conducted an audit of the first Guides, and surveyed
      those responsible for their production, in order to examine the Guides'
      development, content, presentation and dissemination, and to critique the purpose
      of the initiative. METHODS: A semi-structured questionnaire survey of those
      responsible for producing the Guides, and an audit of the Guides produced by
      Primary Care Trusts (PCTs). RESULTS: Most PCTs complied with central guidance
      about structure and content, but in meeting multiple requirements the Guides lost
      their clarity of purpose. The content was dominated by information relating to
      financial and strategic accountability. In producing the Guides, external
      consultation was limited, particularly with the public but also with local
      partnership providers of health and social care. The main issues were the lack of
      a clear focus for Guide information, the level of central direction, the short
      production lead times, difficulties with distribution, and the many competing
      demands being made on PCT resources. CONCLUSIONS: Guide content should be clearly
      focused on information that the public wants. Greater responsibility should be
      devolved to front line PCT staff to determine content in consultation with local
      users.

PMID- 15860055
TI  - Evaluating health-care: the perspectives of sufferers with upper limb pain.
AB  - BACKGROUND AND AIMS: There is considerable uncertainty over the diagnosis,
      treatment and management of upper limb pain, which has implications for patient
      care. Research into patient experiences and evaluation of health-care has been
      neglected and the study presented here aims to fill this gap. METHODS: A two
      staged, mixed methodology was adopted. Phase 1 involved a postal survey of a
      random sample (n = 2781) of the working age population (25-64) of an area in
      south-west England. Phase 2 consisted of follow-up, informal face-to-face
      interviews with a purposive sample of 47 informants identified, according to pre
      defined criteria, from the survey sample. RESULTS: Our data showed that concerns
      about the effectiveness of treatments for alleviating pain were fundamental to
      users' evaluations of both orthodox and non-orthodox health-care. This took
      priority over the need for a diagnosis and other information. There was a general
      recognition that the treatments available were, at least, only partially
      effective and the pragmatic approach led some to eventually withdraw from both
      orthodox care and complementary and alternative medicines (CAM). CONCLUSION:
      Patients' priorities for health-care, in this context, were perceived to involve
      the provision of treatments which alleviated pain and were safe and painless.
      Orthodox and non-orthodox care needed to be more closely integrated into primary
      care services.

PMID- 15860056
TI  - Informed choice and public health screening for children: the case of blood spot
      screening.
AB  - OBJECTIVE: To examine parents' and health professionals' views on informed choice
      in newborn blood spot screening, and assess information and communication needs.
      DESIGN AND PARTICIPANTS: A qualitative study involving semi-structured telephone
      interviews and focus groups with 47 parents of children who were either found to
      be affected or unaffected by the screened conditions, and 35 health professionals
      with differing roles in newborn blood spot screening programmes across the UK.
      RESULTS AND CONCLUSIONS: Parents and health professionals recognize a tension
      between informed choice in newborn blood spot screening and public health
      screening for children. Some propose resolving this tension with more information
      and better communication, and some with rigorous dissent procedures. This paper
      argues that neither extensive parent information, nor a signed dissent model
      adequately address this tension. Instead, clear, brief and accurate parent
      information and effective communication between health professionals and parents,
      which take into account parents' information needs, are required, if informed
      choice and public health screening for children are to coexist successfully.

PMID- 15860057
TI  - Citizen deliberation in setting health-care priorities.
AB  - BACKGROUND: Citizen deliberation is a prominent theme in health policy
      literature. It is believed that citizens who deliberate may influence the setting
      of public health-care priorities. Currently, in some jurisdictions, citizens are
      members of community health boards, and thus have a forum to articulate and share
      values that could affect the reduction of health inequalities within their
      communities. However, there is little conceptual clarity on the character of
      citizen deliberation, or, more specifically, how citizens may articulate and
      share values. OBJECTIVES: This paper reviews the literature on citizen
      deliberation in setting health-care priorities; discusses potential challenges
      for citizens in setting health-care priorities; outlines a developing theory of
      citizen deliberation; describes how citizens may articulate and share values that
      ground their health-care priorities and outlines implications of a developing
      theory of citizen deliberation, its relevance to UK study findings, and to
      community health boards in setting health-care priorities. CONCLUSIONS: As
      members of community health boards, citizens can evaluate their subjective
      experiences. In reasoning about embedded values, citizens may gain insight into
      the kind of community they aspire to be, and, in that process, examine their
      intentions, including whether to serve self or other(s). Citizens who articulate
      and share values such as respect, generosity or equity may justify health-care
      priorities that create opportunities for all community members to gain mastery
      over their lives.

PMID- 15860061
TI  - The 66th Annual Meeting of the Society for Investigative Dermatology. May 4-7,
      2005, St. Louis, Missouri. Abstracts.

PMID- 15860064
TI  - Determinants of physical activity and low-fat diet among low income African
      American and Hispanic middle school students.
AB  - African Americans, Hispanics, and those with low income experience
      disproportionate health problems that can be prevented by physical activity and a
      lower fat diet. In this descriptive cross-sectional study, antecedents of diet
      and exercise within the Health Promotion/Transtheoretical Model were examined
      among low-income African American and Hispanic seventh-grade students (n = 127).
      Total support was associated with higher physical activity for girls. African
      Americans perceived greater social support for activity than Hispanics. Family
      models and support for physical activity and low-fat diet were greater as family
      income increased. However, higher family role models and lower dietary fat were
      found among the lowest income Hispanic students' residing ZIP code with a higher
      concentration of Hispanics and greater availability of Hispanic foods and
      culture. A school-based approach may be useful to build peer support for physical
      activity and lower dietary fat. Parish nurse or clinic settings may be most
      appropriate for building family role models and support. Living in a neighborhood
      with traditional Hispanic culture and foods appears to have ameliorated the
      harmful effects of lower income, although further study with larger samples
      followed over time is needed.

PMID- 15860065
TI  - Prevalence of partner violence against 7,443 African American, White, and
      Hispanic women receiving care at urban public primary care clinics.
AB  - Given inconclusive findings regarding racial/ethnic differences in risk for
      intimate partner violence (IPV), this study will estimate annual prevalence and
      severity of IPV and associated risk factors of homicide among a multiethnic
      population of English- and Spanish-speaking African American, White, and Hispanic
      women receiving public primary health care. A personal interview survey was
      conducted using three measurement instruments including a brief two-question
      screen. The sample consisted of 7,443 women, aged 18-44 years, receiving care at
      urban, primary health care clinics in southern Texas. White women disclosed abuse
      at a rate of 8.9%, followed by African American women at 6.0% and Hispanic women
      at 5.3%. More abuse was reported by White and African American women compared to
      Hispanic women. Use of a brief two-question screen provides racial/ethnic
      specific surveillance data for patient care programming and can track progress
      toward decreasing violence against women.

PMID- 15860066
TI  - Risk factors for tuberculosis among inmates: a retrospective analysis.
AB  - This paper examined risk factors associated with TB among inmates, over a 7-year
      period, and the association of ethnicity and gender with these risk factors. We
      performed retrospective analysis of data on former inmates from a county jail. TB
      status at admission was explained with demographics, behavioral risk factors, and
      incarceration factors. We examined ethnicity and gender defenses on the risk
      factors. A total of 441 TB cases and 478 non-TB cases were included. Inmates were
      more likely to have TB if they were whites, unmarried, homeless, alcohol abusers,
      and HIV positive. Inmates with TB had even lower socioeconomic status and more
      behavioral risk factors than other inmates. They had fewer incarcerations and
      less serious crimes, but longer jail stays. TB risk factors differed by ethnicity
      and gender. TB control in jails requires intervention in the communities where
      inmates live. Correctional health is a critical part of public health. Public
      health nurses are responsible for better understanding and improving health care
      for this high-risk and difficult-to-reach population.

PMID- 15860067
TI  - Cancer risk factors among Southeast Asian American residents of the U.S. Central
      Gulf Coast.
AB  - This study profiles aggregate-specific cancer risk factors of Southeast Asian
      Americans residing along the Central Gulf Coast in the United States. An
      investigator-designed cross-sectional survey was conducted with 332 volunteer
      Southeast Asian community residents aged 18 years and above. Aggregate-specific
      cancer risk factors include high prevalence of hepatitis, high smoking and
      drinking rates in men, extended ultraviolet light exposure without protection,
      low colorectal and prostate cancer screening rates, and knowledge deficits of
      cancer and cancer screenings. Based on the study findings, progress toward the
      targets of the Alabama Comprehensive Cancer Control Plan: 2001-2005 is evaluated
      and compared to available national data. Implications for public health nursing
      practice and future research are also addressed. In particular, the study
      findings underscore the importance of developing culturally tailored
      interventions to reduce cancer risk factors in this underserved Asian American
      population.

PMID- 15860068
TI  - Gender differences in health-promoting lifestyles of African Americans.
AB  - Despite progress in meeting Healthy People 2010 goals, African American (AA) men
      and women have higher mortality and morbidity rates as compared with Caucasian
      Americans. These may be attributed to lifestyle behaviors; however, this is a
      complex, multifactorial problem. The purpose of this study was to examine gender
      differences among AA lifestyle behaviors. A descriptive comparative design was
      used. The sample consisted of 223 AAs residing in southeastern United States. The
      health-promoting lifestyle profile (HPLP) was used to measure health-promoting
      behaviors. Independent t-test analysis revealed no statistically significant
      gender differences for total HPLP scores, t(220) = -1.49, p = 0.14. When
      controlling for income, education, and marital status, no significant
      interactions were seen with gender on HPLP. Independent t-test analyses revealed
      statistically significant differences for interpersonal relationship support,
      t(221) = -1.97, p = 0.05, health responsibility, t(214) = -2.46, p = 0.02, and
      nutrition t(219) = -3.27, p < 0.01, with women scoring higher than men. Although
      gender differences in AAs are evident for specific health-promoting lifestyle
      behaviors, these differences become less dominant when education and marital
      status were used as covariates.

PMID- 15860069
TI  - Screening for nutritional risk in community-dwelling old-old.
AB  - Screening tools for detecting declining nutrition in community-dwelling old-old
      are few and problematic. The purpose of this study was to identify the leading
      risk factors associated with noninvasive measures of poor nutritional status
      among elders aged 80 or older still living independently in the community. This
      cross-sectional descriptive study included 68 community-dwelling old-old (average
      age 85.7). Participants were recruited by parish nurses. In-home interviews were
      conducted. Relationships between five well-established measures of nutritional
      risk factors and two measures of nutritional status, body mass index (BMI)
      categories, and unintentional weight loss were examined. Depression and the food
      pyramid groups with adequate amounts eaten were predictive of unintentional
      weight loss in the previous 6 months (p = 0.013) but not of high or low BMI. In
      this sample, 25% were obese. Screening for depression and food intake may be
      useful in predicting nutritional decline among community-dwelling old-old and
      point to targeted interventions in a population who are large users of health
      care dollars.

PMID- 15860070
TI  - The effectiveness of empowering in-service training programs for foreign nurse
      aides in community-based long-term care facilities.
AB  - The objective of the study was to examine the effectiveness of empowering in
      service training programs for foreign nurse aides working in community-based long
      term care (LTC) facilities. The design was a pretest and post-test design with
      experiment and control groups. The sample consisted of purposeful sampling from
      10 LTC facilities in the Shihlin and Peitou areas of Taipei. A total of 35
      foreign nurse aides participated in this study; 16 in the experimental group and
      19 in the control group. The experimental group attended the training program for
      a 3-month period, whereas the control group did not receive any training. The
      research findings reveal that the training program was effective in increasing
      the work stress of workload/scheduling (Z = 2.01, p </= 0.05), meaning that the
      training program has raised the awareness of work stress for foreign nurse aides.
      The results could be used as a reference when considering the development of in
      service training programs in LTC facilities.

PMID- 15860071
TI  - The public health nursing role in rural Japan.
AB  - The objective of this study was to describe the activities of the public health
      nurses in the local community. The setting was a small rural town in central
      Japan. The design was a descriptive study based on informant interviews
      supplemented by participant observation. The sample consisted of five public
      health nurses, four health care workers in other fields, and seven clients, all
      living in the same town. Each participant was interviewed individually.
      Interviews focused on the participants' understanding of what public health
      nurses actually do. Semistructured interview guides for each group of
      participants served as a framework to elicit participants' views on the
      activities of the public health nurses. Analysis of interview transcripts
      indicated that commitment was a core concept in the role of the public health
      nurses. Linked to this central theme were three constructs describing their work:
      identifying the real needs of clients, responding appropriately and promptly, and
      establishing trust relationships. The interviews indicated considerable public
      support for collaborative activities involving public health nurses, other health
      care workers, and community members. Implications for public health nurses'
      expanded role in Japan in relation to other health care professionals are
      addressed.

PMID- 15860073
TI  - Modifications of graduate public/community health nursing internships to
      facilitate compliance with Institutional Review Board and Health Insurance
      Portability and Accountability Act (HIPAA) regulations.
AB  - This paper describes the changes that were made to a two-semester graduate
      internship course to facilitate student compliance with Institutional Review
      Board (IRB) and agency requirements for compliance with the Privacy Rule of the
      Health Insurance Portability and Accountability Act (HIPAA). Students now spend
      the first semester of the internship developing collaborative relationships with
      the agency and conceptualizing, planning, and developing all aspects of the
      project, including preparing materials for an IRB review. A series of workshops
      about the IRB process, the Privacy Rule of HIPAA, and on-line resources have been
      developed. A password-protected web site and other resources were developed for
      preceptors. The result of the changes has been primarily positive. By having to
      conceptualize and develop the entire project at the beginning, students
      demonstrate a better understanding of program development and evaluation. Their
      writing has markedly improved. Preceptors like the course revisions, the
      convenience of on-line resources, and the enhanced course focus on the protection
      of health care information and of potential participants in health education
      programs or program evaluation projects.

PMID- 15860072
TI  - A case study of a distance-based public health nursing/community health nursing
      practicum.
AB  - Facilitating a distance-based public health/community health nursing practicum
      for RN to BSN students posed challenges and opportunities. Challenges included
      time involved in arranging the practicum, relationship building with agencies and
      staff, communicating with students, and the need for flexible practicum
      scheduling. Exposure to practice models from across the nation allowed students
      to compare and contrast these public health nursing models. Programs planning to
      offer this type of course should consider faculty workload particularly during
      the semester prior to teaching the practicum.

PMID- 15860074
TI  - Beverly C. Flynn, an oral history with a 20th century activist.
AB  - Beverly Collora Flynn, Ph.D., R.N., F.A.A.N., when asked what she believes her
      legacies will be, cites achievements that have sustained her professionally and
      personally. Through her work in the Institute of Action Research for Community
      Health at Indiana University School of Nursing and her work in Healthy Cities,
      she further developed the application of primary health care and community health
      promotion concepts into practice. A theme that emerges from her story is that of
      recognizing new approaches to meeting the health needs of communities and
      developing them into lasting practices. Flynn's long marriage to Pat and rich
      family life, including two children Bryan and Nicole have been balanced with her
      professional commitments and have been a source of strength for her as a person
      and as a nurse. Dr. Flynn is one of those exceptional individuals we honor, by
      telling her story as she told it to us in July, 2004 for this series on
      outstanding public/community health nursing leaders of the twentieth century.

PMID- 15860076
TI  - The integration of genomics into paediatric and perinatal epidemiology:
      guidelines for submitting human genome epidemiology (HuGE) reviews.

PMID- 15860077
TI  - Risk factors for spontaneous preterm birth among Aboriginal and non-Aboriginal
      women in Manitoba.
AB  - In the province of Manitoba, the incidence of preterm birth has been increasing
      and the rate is higher among Aboriginal than non-Aboriginal women. The purpose of
      this study was to identify risk factors for spontaneous preterm birth in Manitoba
      women, and to compare risk factors among Aboriginal and non-Aboriginal women. A
      case-control study was performed at two tertiary care hospitals in Winnipeg,
      Manitoba, Canada from October 1999 to December 2000. Cases delivered a live
      singleton infant at < 37 weeks gestation (n = 226; 36% Aboriginal), while
      controls delivered between 37 and 42 weeks gestation (n = 458; 38% Aboriginal).
      An interview was conducted with each subject on the postpartum unit, and
      information was collected from the health record. Using stratified analyses to
      control for race/ethnicity, several risk factors for preterm birth had a uniform
      effect measure across strata, while others demonstrated heterogeneity. After
      adjusting for other maternal characteristics in a multivariable logistic
      regression model, significant risk factors for all women included previous
      preterm birth, two or more previous spontaneous abortions, vaginal bleeding after
      12 weeks gestation, gestational hypertension, antenatal hospitalisation, and
      prelabour rupture of membranes. In addition, potentially modifiable risk factors
      included low weight gain during pregnancy and inadequate prenatal care for all
      women, and high levels of perceived stress for Aboriginal women. These modifiable
      risk factors lend themselves to public health interventions, and should be
      targeted in future prevention efforts.

PMID- 15860078
TI  - Does participation in a nurse visitation programme reduce the frequency of
      adverse perinatal outcomes in first-time mothers?
AB  - Children First (C1), a nurse home visitation programme for first-time mothers,
      was implemented statewide in Oklahoma in mid-1997. The objective of this study
      was to compare the risks of low (< 2500 g) and very low birthweight (< 1500 g),
      preterm (< 37 weeks) and very preterm (< 30 weeks) deliveries and infant
      mortality between mothers participating and not participating in C1. All 239,466
      Oklahoma birth certificates were reviewed. The C1 and birth certificate databases
      were matched to identify C1 participants. Mother's age at delivery, education
      level, race, marital status, prior pregnancy loss or pregnancy risk factors,
      birthweight and gestational age at delivery were measured from the birth
      certificates. Death certificates were matched to the birth certificates to
      identify infant deaths. A Bayesian multivariable logistic regression was used to
      analyse the data. Among single mothers without pregnancy risk factors, the risks
      of all study outcomes were lower for participants in C1: adjusted odds ratio
      (aOR) 0.89, [95% Bayesian Credible Interval (BCI) 0.79, 1.00] for preterm
      delivery; aOR 0.71, [95% BCI 0.50, 0.98] for very preterm delivery; aOR 0.86,
      [95% BCI 0.75, 0.98] for low birthweight; aOR 0.77, [95% BCI 0.56, 1.02] for very
      low birthweight and aOR 0.36, [95% BCI 0.17, 0.63] for infant mortality. These
      risk reductions were not observed among married mothers. In both single and
      married mothers, the presence of pregnancy risk factors reduced the impact of C1
      on lowering the risk of low birthweight and preterm deliveries. The C1 programme
      targets young, pregnant women of low socio-economic level. We found that among
      single mothers, the risks of perinatal adverse outcomes are reduced or similar to
      those found in non-participating mothers. A reduced effect of C1 in the presence
      of pregnancy risk factors may be because mothers with pregnancy risk factors who
      did not participate in C1 received better prenatal care, or that C1 interventions
      do not impact these particular factors. C1 shows promise in reducing infant
      mortality in single mothers. Lower incidence of preterm and very preterm
      deliveries is especially interesting and future analyses should focus on
      isolating programme components specifically associated with influencing these
      outcomes.

PMID- 15860079
TI  - An assessment of pregnancy-related mortality in the United States.
AB  - Deaths from pregnancy complications remain an important public health concern.
      Nationally, two systems collect information on the number of deaths and
      characteristics of the women who died from complications of pregnancy. The
      Centers for Disease Control and Prevention's (CDC) National Center for Health
      Statistics (NCHS) reports maternal mortality through the National Vital
      Statistics System (NVSS); CDC National Center for Chronic Disease Prevention and
      Health Promotion's Pregnancy Mortality Surveillance System (PMSS) conducts
      epidemiological surveillance of pregnancy-related deaths. The numbers of deaths
      reported by these two systems have differed over the past two decades; our
      objective was to determine the magnitude and nature of these differences. For
      1995-97, we compared maternal deaths in the NVSS with pregnancy-related deaths in
      PMSS for the 50 States, Washington DC and New York City. Pregnancy-related deaths
      whose underlying cause was assigned to ICD-9 codes 630-676 by NVSS were
      classified as maternal deaths; those coded outside 630-676 were not. There were
      1387 pregnancy-related deaths in PMSS and 898 maternal deaths in the NVSS; 54% of
      these deaths were reported in both systems, 40% in PMSS only, and 6% in NVSS
      only. Pregnancy-related deaths due to haemorrhage, embolism, and hypertensive
      complications of pregnancy were proportionately more often identified by NVSS as
      maternal deaths than those from cardiovascular complications, medical conditions
      or infection. From the 1471 unduplicated deaths classified as maternal or
      pregnancy-related from either reporting system, we estimated a combined pregnancy
      related mortality ratio of 12.6/100,000 live births for 1995-97, compared with
      11.9 for PMSS only and 7.5 for NVSS only. The identification and classification
      of these events is dependent on the provision of complete and accurate cause-of
      death information on death certificates. Changes in the guidelines for coding
      maternal deaths under ICD-10 may change the relationship in the number of deaths
      resulting from pregnancy reported by these two systems.

PMID- 15860080
TI  - Anthropometric measurements for neonates, 23 to 29 weeks gestation, in the 1990s.
AB  - Reference data describing weight, length, and head circumference (anthropometric
      measurements) at birth were published by Lubchenco and Usher before 1970. Few
      attempts have been made to investigate whether these data are appropriate for
      today's cohort of preterm neonates. We analysed anthropometric data for neonates
      born between 23 and 29 weeks' gestation. Reference charts were developed from the
      measurements obtained from neonatal records, and gestational age, obtained from
      maternal charts, on 975 neonates delivered at four neonatal centres in Michigan
      during 1992 and 1997. The analysis was confined to children with gestational age
      that was consistent or within 7 days by last menstrual period, obstetric
      examination, ultrasound and neonatal determinations. At 23 to 29 weeks'
      gestation, ethnicity and multiple births did not have any significant impact on
      birthweight but girls were lighter. We compared our anthropometric charts with
      those presently being used at many neonatal centres. In our study, physical
      measurements at birth of preterm neonates born between 1992 and 1997 were
      significantly different from those currently used to assess growth status.
      Furthermore data derived from published studies that utilised birth certificates
      with gestational age based on last menstrual period seem to overestimate
      birthweight. For preterm infants, our findings are concordant with recently
      published values from 18 states of the US. Because of improved survival,
      gestational age assessment and perinatal care of preterm neonates, development of
      new reference anthropometric measurements for neonates is overdue. Our Michigan
      data of 23-29 weeks preterm provides new national reference values, which we
      recommend for use in US neonatal centres for extremely preterm neonates.

PMID- 15860081
TI  - A South Australian population-based study of congenital talipes equinovarus.
AB  - The aims of this study were to provide a population-based prevalence for
      congenital talipes equinovarus (CTEV), to conduct an epidemiological
      investigation into the risk factors for CTEV and describe associated features.
      The study used a retrospective case-control design of CTEV notified to the South
      Australian Birth Defects Register between 1986 and 1996 inclusive, linking
      characteristics of mother and baby from the perinatal data collection. The
      prevalence of isolated CTEV was 1.1/1000 total births (n = 231). Four factors
      were significantly associated with an increased risk of CTEV: maternal Aboriginal
      race (ORadj = 2.0; 95% CI 1.1, 3.6), male gender (ORadj = 2.4; 95% CI 1.8, 3.2),
      maternal anaemia (ORadj = 1.8; 95% CI 1.0, 2.9) and maternal hyperemesis (ORadj =
      3.6; 95% CI 1.3, 9.8). The prevalence of CTEV associated with another birth
      defect or syndrome (n = 157) was 0.7/1000 total births. CTEV was associated with
      specific birth defects and also with oligohydramnios when another birth defect
      was present.

PMID- 15860082
TI  - Risk factors for isolated talipes equinovarus in Western Australia, 1980-1994.
AB  - A case-control study based on routinely collected data for a West Australian (WA)
      cohort of births born 1980-94 inclusive was used to identify potential risk
      factors for the foot deformity isolated talipes equinovarus. Race and sex were
      identified as risk factors and risk modifiers of the condition in WA infants. In
      comparison with their female counterparts, Aboriginal males were at greater risk
      of the deformity than Caucasian males (odd ratio [OR] 7.15, 95% confidence
      interval [CI] 2.68, 21.12 vs. OR 1.63, 95% CI 1.24, 2.15 respectively). Sex
      specific risk estimates of the deformity showed that Aboriginal males were at
      more than four times the risk of Caucasian males (OR 4.27, 95% CI 2.30, 8.25
      respectively), but the risk amongst Aboriginal females was not dissimilar to the
      risk amongst Caucasian females (OR 1.12, 95% CI 0.49, 2.45). Intrauterine
      constraint of the fetus was not found to be an important contributing factor to
      the deformity after accounting for the effect of all risk factors modelled in
      multivariable analyses. Indicators of intrauterine constraint including prolonged
      gestation, high infant birthweight, young maternal age (< 20 years) and breech
      presentation were not associated with excess numbers of isolated talipes
      equinovarus cases. Limited numbers of cases associated with other indicators of
      intrauterine constraint, including the specific categories of short maternal
      stature and a twin pregnancy prevented definitive conclusions regarding their
      association with the deformity. Improved data quality for gestational age
      estimates and oligohydramnios status are required before determining the prenatal
      risk impact of season of conception and of reduced amniotic fluid levels,
      respectively, on the occurrence of the deformity.

PMID- 15860083
TI  - Season of birth in valvular heart disease.
AB  - This study demonstrates seasonal variations of birth dates in children with
      congenital valvular heart disease and in adults dying from valvular heart
      disease. The findings are based on the 1989-98 Swiss EUROCAT data, and on 1969-94
      Swiss mortality records. Seasonality was tested with aggregated monthly data
      using Edwards' procedure. Both data sets showed excesses between December and
      March, consistent in different forms of valvular disease and in both sexes.
      Despite the decline of rheumatic heart disease, risk factors causing season of
      birth effects remain relevant for congenital anomalies.

PMID- 15860084
TI  - Editorial: integrating continuous support of the traditional birth attendant into
      obstetric care by skilled midwives and doctors: a cost-effective strategy to
      reduce perinatal mortality and unnecessary obstetric interventions.

PMID- 15860085
TI  - Review Article: cerebrospinal fluid in human African trypanosomiasis: a key to
      diagnosis, therapeutic decision and post-treatment follow-up.
AB  - Human African trypanosomiasis is a lethal parasitic infection with neurological
      involvement. Examination of the cerebrospinal fluid (CSF) plays an essential role
      in diagnosis, selection of treatment and post-treatment follow-up. This paper
      reviews clinical presentation, diagnosis and treatment of the disease, with
      emphasis on CSF characteristics and interpretation of the CSF results for
      therapeutic decision and post-treatment follow-up.

PMID- 15860086
TI  - Early infant growth monitoring--time well spent?
AB  - BACKGROUND: In sub-Saharan Africa, growth monitoring for every infant consumes
      time and resources with no evidence of any benefits. We consider an alternative
      pragmatic approach which provides scheduled monitoring for low birth weight
      infants only, and takes advantage of non-routine clinic visits for normal birth
      weight infants. We investigate the implications for the number of weighing
      episodes and performance as a screening tool using data from a cohort study of
      infants followed-up from birth to 98 days. METHODS: Babies delivered in a Kenyan
      district hospital and enrolled in a birth cohort were weighed at birth and at
      follow-up visits coinciding with their immunizations at 6, 10 and 14 weeks.
      Episodes of illness resulting in clinic visits, hospital admissions or death were
      identified and recorded. RESULTS: Four-fifths (81%) of the 2210 babies weighed
      2500 g or more at birth, of whom 133 (7%) were admitted to hospital or died
      before 14 weeks of age. 85% of the deaths and 67% of admissions occurred within 3
      weeks of birth. Most babies weighing 2500 g or more and who had weight
      measurements grew well. Only 4% of infants were exclusively breastfed at 14 weeks
      of age. Neither universal nor pragmatic growth monitoring was a good screening
      tool among this group of infants for episodes of illness in the short-term.
      Pragmatic monitoring would involve 72% fewer weighing episodes. CONCLUSIONS: A
      pragmatic approach in early infancy would not represent a major change in policy,
      would appear to have no disadvantages and would probably increase the time
      available for implementing interventions of greater benefit such as breastfeeding
      promotion.

PMID- 15860087
TI  - Ecological covariates of Ascaris lumbricoides infection in schoolchildren from
      rural KwaZulu-Natal, South Africa.
AB  - OBJECTIVES: To identify environmental factors that could serve to predict Ascaris
      lumbricoides infection patterns and thus guide control efforts in the absence of
      epidemiological information; to assess whether A. lumbricoides infection is
      positively associated with the soil clay content. METHODS: Information on A.
      lumbricoides infection and re-infection in a cohort of primary schoolchildren and
      interview data on their socioeconomic background and behaviour were combined with
      environmental data using a geographical information system (GIS). Multivariate
      models served to explore the covariation of environmental and infection patterns
      adjusted for possible confounders. RESULTS: Prevalence maps and spatial
      statistics revealed considerable spatial clustering of infection in the small
      study area. Logistic multivariate regression models showed strong positive
      associations of infection with vegetation density measured as the normalized
      difference vegetation index (NDVI) at baseline [odds ratio (OR) for a 10%
      increase: 1.82; 95% confidence interval (95% CI): 1.24-2.68; P=0.002] and after
      re-infection (OR: 2.22; 95% CI: 1.71-2.87; P<0.001). We also found a strong
      negative association of re-infection with the sun exposure of the soil surface as
      estimated from digital elevation models (OR: 0.78; 95% CI: 0.88; P<0.001). The
      soil clay content was only moderately positively associated with infection and re
      infection. Socioeconomic and behavioural variables, although correlated with A.
      lumbricoides infection, did not appear to confound the above associations in the
      demographically homogeneous study area. Spatial analysis of the model residuals
      suggested that as the models accounted for most of the spatial pattern, the model
      standard errors should not be affected by spatial clustering. CONCLUSION: NDVI
      seems to have a high potential for the prediction of A. lumbricoides infection as
      it was strongly associated with infection patterns in the study area. Further
      advantages are that NDVI information is easy to use, affordable and available
      with global coverage.

PMID- 15860088
TI  - Safer injections, fewer infections: injection safety in rural north India.
AB  - BACKGROUND: Unsafe injection practices result in a substantial burden of
      preventable blood-borne viral disease (BBV). The reasons are complex and include
      structural, economic and socio-cultural factors. OBJECTIVE: To describe injection
      related practices in two rural north Indian health settings including the
      contextual factor, highlight some of the challenges facing those endeavouring to
      translate injection safety policies into safe injection practice, and to identify
      appropriate intervention strategies. METHOD: Qualitative data collection
      (participant observation and in-depth interviews) in two rural north Indian
      hospitals with affiliated community-based programmes over a 4-month period. A
      total of 130 h of observation took place in a range of clinical areas
      characterized by frequent use of needles and other sharps, and 40 healthcare
      workers were interviewed. Field notes and interview transcripts were thematically
      analysed. RESULTS: Managers in these health settings were clearly endeavouring to
      promote injection safety by implementing the widespread use of disposable needles
      and syringes and attempting to address the difficult issue of safe healthcare
      waste management. However, some unsafe practices were still occurring: reuse of
      syringes (with and without sterilization) was relatively common, and use of multi
      dose vials, blood sampling, sterilization and disinfection, and healthcare waste
      management were sub-optimal in some instances, placing both staff and patients at
      unnecessary risk of BBV infection. CONCLUSION: Strategies for promoting injection
      safety are necessary if the risk of nosocomial transmission of BBV diseases via
      unsafe injection practices in rural north India is to be minimized.

PMID- 15860089
TI  - Short communication: colour vision and proficiency in diagnostic microscopy.
AB  - The microscopical diagnosis of infectious diseases is an essential medical
      laboratory service in resource-poor countries. We conducted an external quality
      assessment (EQA) of peripheral laboratories in southern Ethiopia using a panel of
      20 ready-prepared sputum and blood smears containing either no pathogens or
      locally common pathogens. Microscopists also undertook a colour discrimination
      test (Farnsworth-Munsell 100 hue test). Twenty microscopists from 10 health
      centres participated. Their microscopy results were compared with that of the EQA
      controllers. Their Kappa indices of agreement ranged from 0.1 to 0.89 (mean+/-SD:
      0.58+/-0.21). Kappa values were analysed according to microscopists' colour
      discrimination ability. The Kappa indices for the correct reading of diagnostic
      smears were associated with the colour vision ability of the technicians. Our
      results suggest that routine quality improvement activities may not achieve their
      desired effect if the colour discrimination abilities of technicians are not
      considered.

PMID- 15860090
TI  - Epidemiological patterns of meningococcal meningitis in Niger in 2003 and 2004:
      under the threat of N. meningitidis serogroup W135.
AB  - Since the Neisseria meningitidis serogroup W135 epidemic in Burkina Faso in 2002,
      the neighbouring countries dread undergoing outbreaks. Niger has strongly
      enhanced the microbiological surveillance, especially by adding the polymerase
      chain reaction (PCR) assay to the national framework of the surveillance system.
      During the 2003 epidemic season, 8113 clinically suspected cases of meningitis
      were notified and nine districts of the 42 crossed the epidemic threshold, while
      during the 2004 season, the number of cases was 3521 and four districts notified
      epidemics. In 2003 and 2004, serogroup A was identified in most N. meningitidis
      from cerebrospinal fluid (CSF) specimens (89.7% of 759 and 87.2% of 406,
      respectively). Although serogroup W135 represented only 8.3% of the meningococcal
      meningitis in 2003 and 7.9% in 2004, and was not involved in outbreaks, it was
      widespread in various areas of the country. In the regions that notified
      epidemics, the proportion of serogroup W135 was tiny while it exceeded 40% in
      several non-epidemic regions. Despite the wide distribution of W135 serogroup in
      Niger and the fears expressed in 2001, the threat of a large epidemic caused by
      N. meningitidis W135 seems to have been averted in Niger so far. There is no
      clear indication whether this serogroup will play a lasting role in the
      epidemiology of meningococcal meningitis or not. As early as in the 1990s, a
      significant but transient increase in the incidence of N. meningitidis serogroup
      X was observed. Close microbiological surveillance is crucial for monitoring the
      threat and for identifying at the earliest the serogroups involved in epidemics.

PMID- 15860091
TI  - The burden of the Leishmania chagasi/infantum infection in a closed rural focus
      of visceral leishmaniasis in Lara state, west-central Venezuela.
AB  - A prospective study was conducted in El Brazilar, Curarigua, Lara State,
      Venezuela, a small rural focus of visceral leishmaniasis (VL) to investigate the
      burden and the evolution of Leishmania infection in the human and canine
      population. The incidence of the disease from February 1998 to February 2002 was
      recorded and two cross-sectional surveys using the leishmanin skin test (LST) and
      immunofluorescent antibody test (IFAT) were carried out. The dipstick test with
      recombinant r-K39 antigen was also applied in 2002. The incidence of the disease
      per year among the population (n=118) during the period of study was 0.004. The
      rate of new infections per year was 0.07 [95% confidence interval (95% CI): 0.15
      1.09]. The overall prevalence of infection measured by LST was not significantly
      higher in 2002 (43.2%) than in 1998 (28.3%), but it was with IFAT [16.3%vs. 4.6%;
      odds ratio (OR): 4.01; 95% CI: 1.03-22.78; P=0.022] which would indicate an
      increasing transmission. The dipstick test only detected infection in children up
      to 10 years (19.4%). Prevalence in dogs was not significantly different in 2002
      (57%) vs. 1998 (33%). The parasite was isolated from dogs and identified by a
      polymerase chain reaction based on telomeric sequences as Leishmania
      chagasi/infantum.

PMID- 15860092
TI  - [Difficulties in partnerships between health professionals and Mutual Health
      Organisations: the case of Maliando in Guinea-Conakry].
AB  - In 1998, a Mutual Health Organization (MHO) was created in the region of Guinee
      forestiere in Guinea-Conakry, West Africa, in the context of the action-research
      project PRIMA (Projet de recherche sur le partage du risque maladie). The aim of
      the project was to test whether, and under which conditions, an MHO can improve
      the access to quality health care. The specificity of the model is double-sided:
      on the one hand, the wish to integrate the organization into the local health
      system through a partnership between MHO and health services; on the other hand,
      the systematic efforts by the local research team to involve health
      professionals, at both the operational and managerial level of the system, in the
      planning and implementation of the MHO. We present the results of a study that
      investigates the health professionals' perception of this model. In April 2000,
      semi-structured interviews were held with 16 health professionals working at the
      different operational, managerial and administrative levels of the Guinean health
      system. The professionals perceive the MHO as an effective strategy to overcome
      financial accessibility problems. However, the interviews highlight the
      uncertainties and worries of the health professionals, their lack of
      understanding of the model, their reluctance even to fully accept it. The
      partnership approach was not internalized. They understand the technical
      instrument, but are confused and uncomfortable in their dialogue with the
      population. This study illustrates the difficulties of establishing a real
      partnership between population and health services, as well as the need for
      proper training and coaching of the health workers in the set-up of MHOs. The
      importance of this aspect was insufficiently recognized by the research team,
      despite its good intentions and its huge investment in organizing exchange
      between stakeholders. An important lesson of this experience is the need for
      promoters to conceive and operate MHO systems in which the expectations and fears
      of the health care providers are better identified and better taken into account.

PMID- 15860093
TI  - Evaluation of antiretroviral therapy results in a resource-poor setting in
      Blantyre, Malawi.
AB  - OBJECTIVE: To evaluate treatment results of the paying antiretroviral therapy
      (ART) clinic of Queen Elizabeth Central Hospital, a large public and teaching
      hospital in Blantyre, Malawi. The only ART was a fixed drug combination of
      stavudine, lamivudine and nevirapine. METHODS: Cross sectional study with
      interviews, laboratory tests (CD4 count, viral load, nevirapine plasma levels,
      transaminases) and data extraction from files. RESULTS: A total of 422 (59%) of
      the patients who started ART since 2000 were lost to follow-up. The 176 patients
      enrolled in the study had good virological and excellent clinical treatment
      results. The most common side effect was peripheral neuropathy. Nevirapine plasma
      levels were remarkably high and associated with successful virological treatment
      results. Two simple adherence questions pertaining to the use of medication in
      the previous 8 days corresponded well with nevirapine levels. The most important
      reasons for non-adherence were shortage of drugs in the hospital pharmacy and
      personal financial constraints. CONCLUSIONS: (1) Many patients were lost to
      follow-up. (2) High nevirapine levels contributed to good therapy results in
      those studied. (3) Simple adherence questions predicted subtherapeutic nevirapine
      levels. (4) Antiretroviral drug supply needs to be uninterrupted and free of
      charge, to prevent avoidable non-adherence.

PMID- 15860094
TI  - Primary care nurses using guidelines in Thailand: a randomized controlled trial.
AB  - BACKGROUND: Nurses run primary health centres in Thailand. We examined whether
      clinical guidelines improved the quality of the care they provide. METHODS:
      Eighteen nurse-led health centres randomized to (a) guidelines, receiving a
      training workshop plus educational outreach visit, with guidelines for children
      (acute respiratory tract infection and diarrhoea) and adults (diazepam
      prescribing and diabetes management) or (b) usual care. Outcomes were changes at
      6 months in antibiotic use, diazepam prescribing, drug costs per patient, and a
      composite process index for diabetes care. RESULTS: Baseline prescribing was high
      for antibiotics (37% of all attendees), and no difference between intervention
      and control sites was detected at follow-up for this variable. In children (0-5
      years old), antibiotics were widely used for acute respiratory tract infection
      (34%), and fell with guidelines (intervention: 42% at baseline to 27% at follow
      up; control: 27-30%, P=0.022), with an associated fall in drug costs per patient.
      Antibiotics were widely prescribed for diarrhoea in children (91%), but no change
      was detected with guidelines. In adults, diazepam prescribing at baseline was
      high (17%), and fell in the guidelines group (intervention: 17-10%; control 21
      18%; P=0.029). Diabetes care was generally good, and changed little with
      guidelines. CONCLUSION: Staff at primary health centres over-prescribe
      antibiotics in children and tranquilizer in adults. Clinical guidelines
      implemented with workshops and educational outreach visits improved some but not
      all aspects of prescribing in the short-term.

PMID- 15860095
TI  - Evaluation of chloroquine (CQ) and sulphadoxine/pyrimethamine (SP) therapy in
      uncomplicated falciparum malaria in Indo-Myanmar border areas.
AB  - Chloroquine (CQ) and sulphadoxine/pyrimethamine (SP) are two first-line
      antimalarials used under the existing Indian National Drug Policy in the north
      eastern region of India bordering several countries including Myanmar. Although
      widespread resistance to antimalarials in Plasmodium falciparum has been reported
      from western Myanmar, information from the Indian side of the border is scarce.
      We studied the therapeutic response to CQ and SP at four sites in Changlang and
      Lohit, two administrative districts of Arunachal Pradesh bordering Myanmar. We
      monitored uncomplicated falciparum malaria patients after treatment with standard
      regimens of CQ and SP for 28 days following the revised in-vivo protocol of the
      World Health Organization. A total of 236 patients, 95 in the CQ group and 141 in
      the SP group, participated. We recorded 23.8% early treatment failures to CQ and
      14.1% to SP; late clinical failures of 14.3 and 12.6%; late parasitological
      failures of 10.7 and 8.1% and adequate clinical and parasitological responses of
      51.2 and 65.2%, respectively. The significantly different treatment failure rates
      seen in Chowkham (furthest from Indo-Myanmar border) and Jairampur/Nampong
      (nearest to Indo-Myanmar border) for chloroquine (Cox proportion hazard ratio
      9.1, P<0.0001) and SP (Cox proportion hazard ratio 7.35, P=0.001) denote a non
      response gradient to the two antimalarials extending from the international
      border. The gradient is probably indicative of the direction of movement of the
      drug-resistant P. falciparum parasite. The utility of chloroquine as the first
      line drug under the present National Drug Policy in these areas needs
      reconsideration.

PMID- 15860096
TI  - The role of sequential administration of sulphadoxine/pyrimethamine following
      quinine in the treatment of severe falciparum malaria in children.
AB  - Sulphadoxine/pyrimethamine (SP) is often administered with quinine in the
      treatment of severe falciparum malaria to shorten the course of quinine. The
      efficacy of SP alone in the treatment of non-severe malaria has been declining
      rapidly in East Africa, raising concerns of the usefulness of a shortened course
      of quinine followed SP. We audited the efficacy of quinine/SP in the treatment of
      severe malaria in Kenyan children. Children with severe falciparum malaria were
      treated with parenteral quinine followed by a single oral dose of SP. A clinical
      evaluation was performed 3 weeks later in which a blood sample was obtained for
      full haemogram, blood slide and analysis of the parasite dihydrofolate reductase
      (DHFR) and dihydropteroate synthase (DHPS) codons, mutations of which are
      associated with resistance to SP. A total of 452 children were enrolled, of whom
      374 completed the study. Fifty-two (13.9%) children were parasitaemic by 3 weeks
      of whom 17 (4.5%) had fever as well. The treatment failure group had a
      significantly higher parasitaemia (129 061 vs. 43 339; P<0.001) and haemoglobin
      on admission, but only admission parasitaemia independently predicted treatment
      failure. Those with treatment failure had a significantly lower rise in
      haemoglobin at 3 weeks compared with treatment successes (9.0 vs. 10.0 g/dl). Of
      the 76 parasite isolates collected before treatment, 40 (53%) were triple mutant
      DHFR-double DHPS (Tp-Db), the genotype most associated with SP resistance. Three
      weeks after SP treatment, the proportion of Tp-Db increased to 72% (31/43). The
      high treatment failure rate and proportion of parasites with Tp-Db negate the use
      of SP to shorten the course of quinine treatment in East Africa.

PMID- 15860097
TI  - Endemic coastal malaria in the Thousand Islands District, near Jakarta,
      Indonesia.
AB  - OBJECTIVES: To conduct malaria surveillance near Jakarta where only imported
      malaria has been described over the past two decades and to characterize
      endemicity and risk to heavily populated peri-urban locations. METHODS: Standard
      cross-sectional malariometric surveys and mosquito collections at the Thousand
      Islands District and developing peri-urban areas of Jakarta. RESULTS: During
      October 2000 outbreak investigations in the Tidung Island group, the slide
      positive rate was 47% (38%Plasmodium falciparum, 7%P. vivax, and 2% mixed
      infections) among 733 persons screened. Very few parasitemic inhabitants were
      symptomatic (<1%), and native residents were more commonly infected than
      immigrants (odds ratio 1.72), consistent with endemic autochthonous transmission.
      Adult and larval mosquito collections detected Anopheles sundaicus. In June 2001,
      prevalence of parasitemia at Pari Island, where sampling was adequate for
      comparison, remained high, 32%vs. 43% previously. Among 1377 individuals screened
      at nearby Tangerang District, a heavily populated mainland suburb dominated by
      fishponds through which many islanders travel to Jakarta, only 19 malaria
      infections were identified, all imported from Pari Island. Entomological
      surveillance in Tangerang identified An. subpictus, An. vagus, and An.
      barbirostris, all considered minor malaria vectors on Java. CONCLUSIONS: Malaria
      is endemic in the Tidung Island group. Imported malaria occurs in the heavily
      populated Tangerang District where coastal development is increasing and vector
      breeding sites and demographic patterns lend increasingly to malaria importation
      and risk of emergent malaria. Careful attention to the impact of coastal
      development activities on vector populations and efforts to prevent introduction
      of An. sundaicus are warranted.

PMID- 15860098
TI  - Applications of evidence-based medicine: cranial cruciate ligament injury repair
      in the dog.
AB  - OBJECTIVE: To evaluate the literature reporting surgical interventions pertaining
      to canine cranial cruciate ligament (CCL) injury using an evidence-based medicine
      paradigm. STUDY DESIGN: Systematic literature review. METHODS: An on-line
      bibliographic search through Medline, PubMed, Veterinary Information Network, and
      Commonwealth Agricultural Bureau Abstracts was performed during August 2004. Two
      hundred and forty resources of information were identified. Studies were compared
      and evaluated with regard to study design (retrospective, prospective,
      randomization), surgical technique, short- and long-term follow-up, and evidence
      classification. RESULTS: Twenty-eight resources qualified to assist with evidence
      classification. No class I or class II studies were present, 5 studies were
      categorized as a class III and 23 studies were categorized as a class IV.
      Seventeen studies were retrospectively designed and 11 studies were prospectively
      designed. Proposed results ranged from a wide variety of subjective findings
      including clinical impression, radiographic analysis, synovial fluid analysis,
      gross pathology, and histopathology. Objective results, although infrequent,
      included force plate analysis and cadaveric biomechanical testing. CONCLUSIONS:
      At this time, the application of evidence-based medicine in analyzing the current
      available evidence suggests that there is not a single surgical procedure that
      has enough data to recommend that it can consistently return dogs to normal
      function after CCL injury. The requirement for assessing and categorizing the
      available evidence becomes increasingly important as more data becomes available
      and the quality of research improves. CLINICAL RELEVANCE: An evidence-based
      medicine paradigm did not provide sufficient evidence favoring 1 surgical
      technique for management of canine CCL injury.

PMID- 15860099
TI  - Ultrasonographic and radiographic assessment of uncomplicated secondary fracture
      healing of long bones in dogs and cats.
AB  - OBJECTIVES: To evaluate the use of ultrasonography (US) to detect bone healing in
      uncomplicated diaphyseal fractures of dogs and cats, and to compare these
      observations with detection of healing by radiography (RG). STUDY DESIGN:
      Clinical study. ANIMALS: Dogs (33) and cats (11). METHODS: RG and brightness mode
      US were used to follow uncomplicated secondary fracture healing. Fractures were
      examined at admission and then every 2-4 weeks until healed or implant removal.
      Temporal differences in definitive detection of healed fracture by imaging
      technique were examined by species, patient age, bone, and fracture type.
      RESULTS: US images obtained during uncomplicated secondary fracture healing were
      consistent with images of fracture healing described in humans. Mean time to US
      diagnosis of a healed fracture (mean 46 days) was significantly shorter than by
      RG (mean 66 days). Mean time until diagnosis of a healed fracture (US and RG) did
      not differ significantly between open and closed treatment. Patients </=7 months
      (n=9) healed significantly faster (P<.05) than animals aged 7-36 months (n=24)
      and animals >36 months (n=11), but there was no significant difference between
      the latter 2 groups. Diagnosis of a healed simple fracture by US was
      significantly quicker than for a comminuted fracture (P<.05), but no difference
      was noted when using RG. CONCLUSIONS: US can be used to evaluate secondary
      fracture healing in biologically treated fractures in dogs and cats. US permits
      detection of a healed fracture earlier than RG. CLINICAL RELEVANCE: Earlier
      diagnosis of a healed fracture by US can prevent unnecessarily long limb
      immobilization and allow earlier dynamization.

PMID- 15860100
TI  - Accuracy of computerized tomographic evaluation of canine radio-ulnar
      incongruence in vitro.
AB  - OBJECTIVE: To evaluate the accuracy of linear measurements obtained from computer
      tomography (CT) images of staged radio-ulnar incongruence in a canine cadaver
      forelimb model. STUDY DESIGN: CT evaluation of induced progressive radio-ulnar
      incongruence in canine cadaveric forelimbs. SAMPLE POPULATION: Eight cadaveric
      canine left forelimbs. PROCEDURE: A type 2 external skeletal fixator (ESF) with
      linear motors was attached to the radius in 8 cadaveric left canine forelimbs.
      Contiguous incremental and helical CT images of the proximal radio-ulnar
      articulation were acquired in the transverse, sagittal and dorsal planes. The
      radius was shortened by 1, 2, and 4 mm increments and scanning protocols were
      repeated at each increment. Digital caliper and CT image analysis measured the
      progressive change in distance between 2 marking spheres and the epiphyseal bone
      surfaces of the radio-ulnar articulation. Statistical analysis of measurements
      from incremental and helical CT acquisitions, and direct and reformatted images
      were compared with inter-sphere distance using Pearson product moment correlation
      coefficients. RESULTS: The reformatted incremental acquisition series at the mid
      coronoid in the oblique plane had the highest correlation coefficient (r-value)
      at 0.908. The mid-coronoid in the dorsal plane had the second highest r-value
      (0.856). The coronoid incisure in the sagittal plane had an r-value of 0.826. The
      reformatted incremental acquisition series at the coronoid incisure in the
      oblique plane had the lowest r-value, 0.592. CONCLUSION: Measurement of
      radioulnar incongruence may be best performed using reformatted incremental
      acquisition CT in the mid-coronoid region in an oblique plane. CLINICAL
      RELEVANCE: Use of the technique reported in this study may enable determination
      of the association, if any, between radioulnar incongruence and developmental
      diseases of the canine elbow.

PMID- 15860101
TI  - Comparison of 3 techniques for ureteroneocystostomy in cats.
AB  - OBJECTIVE: To compare 3 techniques for ureteroneocystostomy in cats. STUDY
      DESIGN: Experimental surgical study. ANIMALS: Fifteen adult cats. METHODS: Cats
      (15) had ureteroneocystostomy with ureteronephrectomy of the contralateral
      kidney: 5 cats had an intravesical mucosal apposition technique (modified
      Leadbetter-Politano; intravesical-MA group), 5 cats had extravesical
      ureteroneocystostomy (modified Lich Gregoir) using a simple continuous suture
      pattern (extravesical-SC group) and 5 cats had an extravesical technique using a
      simple interrupted suture pattern (extravesical-SI group). Renal function was
      evaluated by measuring serum creatinine concentration. Ultrasonographic
      assessment of the kidney and ureteroneocystostomy site was performed the day
      after surgery, twice weekly for 3 weeks and once weekly for the remainder of the
      study. Cats were euthanatized 50 days after surgery. The kidney and ureter
      removed at surgery, the remaining kidney, ureter, ureteroneocystostomy site, and
      bladder were examined histologically. RESULTS: Two extravesical-SC cats were
      euthanatized because of azotemia and uroabdomen, and 1 died acutely at day 4 for
      unknown reasons. In the intravesical-MA and extravesical-SI cats, the serum
      creatinine concentration increased after surgery, peaking at a mean (+/-SD) of
      9.4+/-2.4 mg/dL and 4.9+/-3.3 mg/dL on day 3, and decreasing to 3.4+/-5.7 mg/dL
      and 1.5+/-0.4 mg/dL on day 7, respectively. The extravesical-SI technique was
      associated with consistently lower serum creatinine concentrations for the first
      week after surgery compared with the other techniques. The mean serum creatinine
      concentration was within the reference range in cats in the intravesical-MA and
      extravesical-SI groups by days 10 and 5, respectively. Renal pelvic dilatation
      occurred in all cats but resolved more rapidly in cats after extravesical
      techniques. There was no significant difference in serum creatinine
      concentrations or renal pelvic dilation between the intravesical-MA and
      extravesical-SI techniques. Bladder mass height at the anastomosis site was
      significantly larger and persisted for longer with intravesical-MA technique.
      CONCLUSION: An extravesical-SI technique is seemingly the choice for
      ureteroneocystostomy in cats with undilated ureters. Renal pelvic dilation on
      ultrasound examination should be expected after ureteroneocystostomy in cats.
      CLINICAL RELEVANCE: An extravesical ureteroneocystostomy technique using a simple
      interrupted pattern for anastomosis should be considered in cats undergoing renal
      transplantation.

PMID- 15860102
TI  - Comparison of computer-assisted surgery with conventional technique for the
      treatment of axial distal phalanx fractures in horses: an in vitro study.
AB  - OBJECTIVES: To compare the precision obtained with computer-assisted screw
      insertion for treatment of mid-sagittal articular fractures of the distal phalanx
      (P3) with results achieved with a conventional technique. STUDY DESIGN: In vitro
      experimental study. SAMPLE POPULATION: Thirty-two cadaveric equine limbs.
      METHODS: Four groups of 8 limbs were studied. Either 1 or 2 screws were inserted
      perpendicular to an imaginary axial fracture of P3 using computer-assisted
      surgery (CAS) or conventional technique. Screw insertion time, predetermined
      screw length, inserted screw length, fit of the screw, and errors in placement
      were recorded. RESULTS: CAS technique took 15-20 minutes longer but resulted in
      greater precision of screw length and placement compared with the conventional
      technique. CONCLUSION: Improved precision in screw insertion with CAS makes
      insertion of 2 screws possible for repair of mid-sagittal P3 fractures. CLINICAL
      RELEVANCE: CAS although expensive improves precision in screw insertion into P3
      and consequently should yield improved clinical outcome.

PMID- 15860103
TI  - Gas arthroscopy for removal of osteochondral fragments of the palmar/plantar
      aspect of the metacarpo/metatarsophalangeal joint in horses.
AB  - OBJECTIVE: To evaluate the use of carbon dioxide (CO(2)) gas for joint distention
      during arthroscopy for removal of osteochondral (OC) fragments of the
      palmar/plantar aspect of the metacarpo (MCP)/metatarsophalangeal (MTP) joints in
      horses. STUDY DESIGN: Clinical study. ANIMALS: Horses (26) with OC fragment(s) of
      palmar/plantar aspect of 1 or 2 MCP/MTP joint(s). METHODS: OC fragments were
      removed using arthroscopic technique. Joint distention was maintained by isotonic
      Ringer's acetate at the beginning and at the end of the procedure but during
      fragment removal, CO(2) was used for joint distention. After surgery, fragment
      removal was confirmed by radiography. Horses were discharged the day after
      surgery, and outcome was determined by telephone contact 3-24 months later.
      RESULTS: CO(2) joint distention resulted in a sharp image without villi obscuring
      the operative field. Fragments were identified and completely removed in all
      horses except one where a 1 mm x 3 mm radiodense body was seen on postoperative
      radiographs. In 5 horses, bleeding from the arthroscopic or instrument portal
      precluded optimal visualization when the joint was distended by gas; however,
      repeatedly rinsing the tip of the arthroscope with Ringer's acetate solution
      delivered from the fluid ingress line easily restored joint visualization. No
      specific complications were observed postoperatively. CONCLUSIONS: Joint
      distention by CO(2) permitted optimal visualization of the palmar/plantar aspect
      of the MCP/MTP joints, which facilitated fragment removal. CLINICAL RELEVANCE:
      Gas arthroscopy is a useful technique for removal of OC fragments of the
      palmar/plantar aspect of the MCP/MTP joints in horses.

PMID- 15860104
TI  - Long-term radiographic comparison of tibial plateau leveling osteotomy versus
      extracapsular stabilization for cranial cruciate ligament rupture in the dog.
AB  - OBJECTIVE: Comparison of 2 methods of surgical management of cranial cruciate
      ligament (CCL) injury in large-breed dogs using a radiographic osteoarthrosis
      (OA) scoring system. STUDY DESIGN: Retrospective study. ANIMALS: Client-owned
      dogs (n=66). METHODS: Radiographs were evaluated from dogs weighing >/=22.7 kg,
      with surgical management of CCL rupture using extracapsular repair (ECR) or
      tibial plateau leveling osteotomy (TPLO). Radiographs were taken immediately
      before surgery and >/=12 months later. An OA score was assigned to each set of
      radiographs taken at the preoperative and final examinations by evaluating 32
      specific features of stifle OA. The difference between preoperative and final OA
      scores were subtracted and 2 final score categories of a change </=5 or >5 were
      created. A logistic regression model was used to evaluate the effect of right
      versus left pelvic limb, age, preoperative weight, postoperative weight, days
      from surgery until final radiographic recheck, cranial cruciate status at
      surgery, medial meniscus status at surgery, and ECR versus TPLO. RESULTS: The ECR
      group had 27 stifles (22 dogs) and the TPLO group had 52 stifles (44 dogs). ECR
      dogs had a preoperative weight of 33.4+/-9.3 kg (range 22.7-54.1 kg) and a
      preoperative OA score of 13.0+/-8.4 (range 1-34) compared with TPLO dogs that had
      a preoperative weight of 38.9+/-9.1 kg (range 25-63.9 kg) and preoperative OA
      score of 15.9+/-8.4 (range 4-44). Postoperative weights for ECR and TPLO dogs
      were 33.6+/-9 kg (range 21.8-54.6 kg) and 39.4+/-10.1 kg (range 24-72 kg),
      respectively. Final OA scores were: ECR dogs, 26.3+/-10.8 (range, 10-54); TPLO
      dogs, 23.3+/-9.5 (range, 12-50). Dogs with a final change in OA score of >/=6
      were 5.78 times more likely to have had ECR compared with those that had TPLO as
      stabilization procedure (odds ratio=5.78; Log-likelihood test P-value=.025).
      Other dependent variables were not significant. CONCLUSIONS: Based on logistic
      regression analysis, dogs with larger OA score differences were 5.78 times more
      likely to have had ECR than TPLO. CLINICAL RELEVANCE: Prospective, randomized
      surgical trials with pre-defined objective measures would be required to further
      evaluate the clinical importance of these preliminary findings which suggest that
      TPLO may help stabilize the cranial tibial thrust as originally proposed.

PMID- 15860106
TI  - Preservation of the fistula for reconstruction of the anal canal and the anus in
      atresia ani and rectovestibular fistula in 2 dogs.
AB  - OBJECTIVE: To report a technique for correction of atresia ani and
      rectovestibular fistula with fistula preservation, and outcome in 2 dogs. STUDY
      DESIGN: Case report. ANIMALS: Two intact female puppies. METHODS: The fistula was
      approached by episiotomy. A vertical median perineal incision was made starting
      dorsal to the anal region and extended to surround the fistula. The rectum and
      vagina were separated, and the end of the fistula was sutured to the skin.
      RESULTS: Early postoperative complications included constipation, fecal
      incontinence, and perineal soiling, but long-term outcome was good in both dogs.
      CONCLUSION: With careful dissection, the fistula and internal anal sphincter can
      be preserved and used in the surgical reconstruction of the anal canal and anus.
      CLINICAL RELEVANCE: Preservation of the fistula may provide an internal sphincter
      that contributes to a better functional result during correction of atresia ani.
      A surgical approach that combines episiotomy and perineal incision for separation
      of the vagina and rectum, and preserves the fistula may decrease the risk of
      dehiscence.

PMID- 15860105
TI  - Arthrodesis of the equine proximal interphalangeal joint: a mechanical comparison
      of 2 parallel 5.5 mm cortical screws and 3 parallel 5.5 mm cortical screws.
AB  - OBJECTIVE: To compare the biomechanical characteristics and mode of failure of 2
      techniques using parallel 5.5 mm screws for pastern joint arthrodesis in horses.
      STUDY DESIGN: Randomized block design, for horse (1-5), method of fixation (two
      5.5 mm screws versus three 5.5 mm screws), side (right, left), and end (front,
      hind). Constructs were tested to failure in 3-point bending. SAMPLE POPULATION:
      Twenty limbs (5 cadavers). METHODS: A combined aiming device was used to
      facilitate screw placement. Two parallel 5.5 mm screws were inserted in lag
      fashion in 1 limb of a pair, and three 5.5 mm screws were inserted in the
      contralateral limb. Constructs were then tested in 3-point bending in a dorsal-to
      palmar (plantar) direction using a materials testing machine at a loading rate of
      19 mm/s. Maximal bending moment at failure and stiffness were obtained from
      bending moment-angular deformation curves. RESULTS: There was no significant
      difference between two and three 5.5 mm screw constructs for bending moment and
      stiffness (P<.05). All constructs ultimately failed by bone fracture or screw
      bending. For proximal interphalangeal (PIP) joint arthrodesis constructs loaded
      in 3-point bending, no significant effect of treatment, side, or end on maximal
      bending moment or stiffness was detected. CONCLUSIONS: Two 5.5 mm cortical screws
      inserted in parallel should provide a surgically simpler and equally strong PIP
      joint arthrodesis compared with three 5.5 mm cortical screws. CLINICAL RELEVANCE:
      Two 5.5 mm cortical screws inserted in parallel for PIP joint arthrodesis should
      perform similarly under conditions used in this study, as three 5.5 mm screws
      inserted in a similar manner, when loaded under bending.

PMID- 15860107
TI  - Medial plating for carpal panarthrodesis.
AB  - OBJECTIVE: To describe a technique for carpal panarthrodesis using a medially
      applied dynamic compression plate (DCP) and to evaluate outcome. STUDY DESIGN:
      Retrospective study. ANIMALS: Nine dogs with 10 carpal joint injuries. METHODS:
      Medical records of dogs that had carpal panarthrodesis by medial application of a
      DCP were reviewed. Signalment, cause and type of injury, preoperative treatment,
      operative technique, and postoperative clinical and radiographic outcome were
      retrieved. RESULTS: Screw loosening in the metacarpal bones required surgical
      revision in 3 dogs. The plate was removed because of lick dermatitis in another
      dog. No complications were observed in 6 arthrodeses. All dogs were subsequently
      sound. CONCLUSIONS: Medial application of a DCP is a reliable, reproducible
      method for carpal panarthrodesis. The load on the edge of the plate provides an
      increased area moment of inertia of the plate, enhancing it resistance to bending
      forces. Because of the valgus standing position of the canine carpus, dynamic
      compression is achieved. The DCP is secured to 1-3 metacarpal bones and loosening
      of the implant and bone fractures are expected to occur less frequently. CLINICAL
      RELEVANCE: Medial plating for carpal panarthrodesis is a valid alternative method
      that can be used in dogs with injuries to the carpus for which panarthrodesis of
      the carpal joint is indicated.

PMID- 15860108
TI  - Destructive lesions of the proximal sesamoid bones as a complication of dorsal
      metatarsal artery catheterization in three horses.
AB  - OBJECTIVE: To describe focal destructive lesions of the proximal sesamoid bones
      (PSBs) as a complication of dorsal metatarsal artery catheterization performed
      for direct blood pressure monitoring during equine general anesthesia. STUDY
      DESIGN: Retrospective study. ANIMALS: Three client-owned horses. METHODS: A
      dorsal metatarsal artery was catheterized in each of 3 horses for direct blood
      pressure monitoring during anesthesia. Radiography, ultrasonography,
      synoviocentesis, and arthroscopy were used to diagnose postoperative lameness
      that occurred in the limb used for blood pressure monitoring. RESULTS: Horses
      developed severe lameness, localized to the fetlock region of the catheterized
      limb within 21 days of surgery. Antibiotic therapy was administered. Surgical
      debridement was possible in 1 horse. Two horses that had lesions that were
      inaccessible, failed to respond to medical management and were euthanatized. The
      3rd horse that had surgical debridement of affected bone, survived. Changes in
      hospital protocol, by improving aseptic technique during catheter insertion and
      use of new manometer tubing and heparinized saline for each arterial catheter
      inserted in the dorsal metatarsal artery, have eliminated this complication.
      CONCLUSIONS: Diagnosis and treatment of destructive lesions of the PSB were
      difficult. Strict aseptic technique should be followed during insertion of
      arterial catheters. CLINICAL RELEVANCE: Focal destructive lesions of the PSB
      subsequent to dorsal metatarsal arterial catheterization is a rare but serious
      complication of equine anesthesia.

PMID- 15860109
TI  - Extensive nasal septum resection in horses using a 3-wire method.
AB  - OBJECTIVE: To describe a surgical technique for, and report outcome after,
      extensive nasal septum resection in horses with congenital or acquired septal
      diseases. STUDY DESIGN: Retrospective study. ANIMALS: Horses (5) with nasal
      septal deformity. METHODS: Under general anesthesia, obstetrical wires were
      preplaced around the ventral, caudal, and dorsal aspects of the nasal septum by
      combinations of manual guidance (ventral and caudal wires) and use of a trephine
      hole on the dorsal mid-line (dorsal and caudal wires). The rostral part of the
      septum was incised with a scalpel and the ventral, dorsal, and caudal septal
      incisions were made with the preplaced wires. After septum removal, the nasal
      cavity packed with a tampon and a temporary tracheotomy was performed. RESULTS:
      The diseased nasal septum was completely removed in all horses. It was possible
      to direct the caudal cut at a sufficient angle so that the remaining stump was in
      a wide part of the nasal passage, where it would have minimal effect on airflow.
      Four horses healed, and returned to intended use but continued to make a slight
      respiratory noise during exercise. At 13 months after surgery, 1 horse with a
      concurrent wry nose was retired from race training after 2 additional surgeries
      failed to relieve exercise intolerance at high speed. CONCLUSIONS: The 3 wire-cut
      method of nasal septum resection was technically easy to perform and safe,
      allowed return to function in most horses, and produced an excellent cosmetic
      appearance. CLINICAL RELEVANCE: This technique for nasal septum resection allows
      removal of a large portion of the nasal septum and provides a safe alternative to
      conventional techniques of nasal septum resection in the horse.

PMID- 15860110
TI  - Use of an ultrasonically activated scalpel for splenectomy in 10 dogs with
      naturally occurring splenic disease.
AB  - OBJECTIVE: To evaluate the safety and efficacy of an ultrasonically activated
      scalpel for performing splenectomy, with minimal ligation, in dogs. STUDY DESIGN:
      Prospective clinical study. ANIMALS: Dogs (10) with naturally occurring splenic
      disease. METHODS: Between October 2003 and February 2004, splenectomy was
      performed using an ultrasonically activated scalpel and a double seal method, in
      10 dogs with naturally occurring splenic disease. Time for splenectomy and number
      of ligatures required were recorded. Intraoperative hemostasis, device ease of
      use, postoperative hemorrhage, and short-term survival were evaluated. RESULTS:
      Mean operative time for splenectomy, exclusive of celiotomy and closure, was 18
      minutes (range, 8-25 minutes). The mean number of ligatures needed to perform
      splenectomy was 1 (range, 0-2 ligatures). One dog hemorrhaged from the splenic
      vein after ultrasonic scalpel transection of a vessel >5-mm diameter and required
      a ligature. The ultrasonic scalpel was easy to use, with a minimal learning
      curve. None of the dogs had postoperative abdominal hemorrhage; 9 dogs were
      discharged and 1 dog was euthanatized because of septicemia. CONCLUSION:
      Ultrasonic activated scalpel may be used to achieve efficient and safe hemostasis
      of the splenic vascular pedicle in dogs with minimal need for vascular ligation.
      CLINICAL RELEVANCE: Ultrasonic scalpels can be used to perform splenectomy in
      dogs with naturally occurring splenic disease.

PMID- 15860111
TI  - A review of spontaneous neoplasia in baboons (Papio spp.).
AB  - The baboon has become an increasingly important animal model and accurate
      information on baboon neoplasia is frequently required for biomedical research.
      To satisfy this demand, a complete literature search was carried out. Two hundred
      and four spontaneous neoplasms were found in published literature: 53 cases were
      male (26%), 76 were female (37%); sex was not reported in 75 cases (37%). Ages
      ranged from 3 months to 31 years (mean 14.1 years) in the 93 cases that reported
      them. Spontaneous neoplasms have been documented in Papio cynocephalus and Papio
      hamadryas as well as in most subspecies and hybrid combinations. The organ
      systems affected in descending order of number of neoplasms were hematopoietic (n
      = 53, 26%), alimentary (n = 52, 25%), urogenital (n = 35, 17%), integumentary (n
      = 26, 13%), endocrine (n = 14, 7%), nervous (n = 12, 5%), musculoskeletal (n = 4,
      2%) and respiratory (n = 3, 1%). There were five miscellaneous neoplasms (2%)
      that could not be classified by system. Lymphosarcoma was the most common
      neoplasm (n = 51, 25%), and adenocarcinomas were second (n = 23, 11%), followed
      by squamous cell carcinomas (n = 10, 5%). Malignant cases numbered 114 (56%); 87
      cases were (43%) benign. The malignancy of three cases (1%) was unreported.

PMID- 15860112
TI  - Characterization of an immortalized oviduct cell line from the cynomolgus monkey
      (Macaca fascicularis).
AB  - To establish reproductive biological techniques in mammals, it is important to
      understand the growth environment of the embryo. Oviduct epithelial cells are in
      close proximity to the embryo during pre-implantation development. We, therefore,
      established an immortalized oviduct epithelial cell line from the cynomolgus
      monkey, evaluated the usefulness of these cells as feeder cells for embryo
      culture, and investigated the gene expression of several growth factors and
      cytokines in the cells. The immortalized cells were positive for the anti
      cytokeratin antibody, as determined by immunocytochemistry, indicating that they
      are epithelial. They also expressed oviductin, which is specific to oviduct
      epithelial cells, glyceraldehyde-3-phosphate dehydrogenase (control), leukemia
      inhibitory factor, vascular endothelial growth factor, epidermal growth factor,
      insulin-like growth factor 1, transforming growth factor beta-2, and interleukin
      4. Mouse embryo development was improved when the immortalized cells were used as
      feeder cells. This cell line is also useful for studying the factors secreted by
      oviduct epithelial cells.

PMID- 15860113
TI  - Ovarian follicular development stimulated by leuprorelin acetate plus human
      menopausal gonadotropin in chimpanzees.
AB  - We attempted ovarian stimulation using gonadotropins in 14 chimpanzees. Subjects
      were given a single administration of leuprorelin acetate, followed by repeated
      administration of human menopausal gonadotropin (hMG) for 16-21 days. During the
      dosing period, the ovarian follicle diameter and count were measured by
      transvaginal ultrasonography. The hormone administration induced the development
      of multiple follicles, and multiple oocytes were subsequently retrieved. However,
      the follicle count was decreased, suggesting atresia, in some subjects.
      Statistically, the final follicle diameter was dependent on the dosing duration
      and the hMG dose in the late stage, while the maximum follicle count during hMG
      administration was dependent on age and the hMG dose in the early stage. Five
      subjects showed mild ovarian hyperstimulation syndrome (OHSS)-like symptoms with
      a high serum estradiol (E2) concentration. These results suggest that leuprorelin
      acetate plus hMG administration successfully stimulates the development of
      multiple ovarian follicles for oocyte retrieval and that the serum E2
      concentration is predictive of OHSS-like symptoms in chimpanzees.

PMID- 15860114
TI  - Comparison of the effects of Percoll and PureSperm on the common marmoset
      (Callithrix jacchus) semen.
AB  - Density gradient centrifugation is a widely used technique for the separation of
      motile from non-motile sperm, for the removal of contaminating agents such as
      bacteria and viruses, and for the removal of seminal plasma or cryoprotectant. In
      the choice of a density gradient medium for a new species, it is important to
      perform toxicity tests. The present study was carried out to evaluate the
      potential toxic effects of two silica-based density gradient products (Percoll
      and PureSperm), on the sperm of the common marmoset. We assessed two different
      batches of Percoll (polyvinylpyrrolidone (PVP)-coated colloidal silica particles)
      and one of PureSperm (saline-coated colloidal silica suspension) by means of a
      computer-aided sperm analysis on semen collected by vibrostimulation. The results
      showed that although some of the sperm patterns of movement and viability changed
      significantly over time, and provide a first description of marmoset sperm
      motility changes under capacitating conditions, there was no significant
      difference in the sperm treated with Percoll or PureSperm in comparison with the
      control. We conclude that simple exposure to either of these products does not
      have a negative effect on viability or motility of marmoset sperm.

PMID- 15860115
TI  - Treatment of myocardial dysfunction and pulmonary oedema in an infant chimpanzee.
AB  - The care of any critically ill infant requires special technical equipment for
      monitoring of cardiac and pulmonary functions including mechanical ventilators
      and blood gas analysers. The present paper describes the treatment of myocardial
      dysfunction and pulmonary distress, complicated by severe brain oedema in an
      infant chimpanzee admitted to an intensive care unit in the Department of
      Neonatology of the Children's Hospital of the University of Leipzig. The
      condition of the chimpanzee was diagnosed and monitored by standard clinical
      tooos including radiography, echocardiography, cerebral Doppler sonography and
      laboratory parameters. The chimpanzee was treated in close cooperation between
      veterinarians and paediatricians.

PMID- 15860116
TI  - Hematological and serum biochemical values in cynomolgus monkeys anesthetized
      with ketamine hydrochloride.
AB  - The effects of ketamine anesthesia on both hematological and serum biochemical
      variables were investigated in 19 male and 15 female cynomolgus monkeys. Blood
      samples were obtained from the cephalic vein within 30 minutes of an
      intramuscular injection of ketamine hydrochloride (10 mg/kg). Ketamine anesthesia
      caused a reduction in leukocyte counts and a significant reduction in lymphocytes
      percentages. Ketamine anesthesia also increased the serum activities of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and creatine phosphokinase
      (CPK), but reduced the serum concentrations of glucose, inorganic phosphate,
      sodium and potassium. The alterations of hematological and serum biochemical
      values will be discussed. These alterations should be considered when designing
      studies for and interpreting data from cynomolgus monkeys.

PMID- 15860117
TI  - Molecular cloning and in vitro evaluation of an infectious simian-human
      immunodeficiency virus containing env of a primary Chinese HIV-1 subtype C
      isolate.
AB  - Human immunodeficiency virus (HIV) clade C is the most prevalent subtype and
      accounts for approximately 50% of all HIV infections worldwide. In China, the
      prevalent HIV strains are B'/C subtypes, in which the envelope belongs to subtype
      C. To evaluate potential AIDS vaccines targeting Chinese viral strains in non
      human primate models, we constructed an infectious simian-human immunodeficiency
      virus (SHIV) that expresses most of the envelope of a primary HIV strain, which
      was isolated from a HIV-positive intravenous drug user from XinJiang province in
      China. The resulting chimeric SHIV-XJ02170 was infectious in human, rhesus monkey
      and cynomolgus monkey peripheral blood mononuclear cells (PBMC) and used CCR5
      exclusively as coreceptor.

PMID- 15860120
TI  - Expression levels of genes for ATP-binding cassette transporters and sterol 27
      hydroxylase in liver and intestine of baboons with high and low cholesterolemic
      responses to dietary lipids.
AB  - Baboons with high and low lipemic responses to dietary lipids differ in
      intestinal cholesterol absorption and hepatic cholesterol metabolism. ATP-binding
      cassette (ABC) transporters play an important role in cholesterol absorption and
      hepatic cholesterol metabolism. Using frozen tissues from high- and low
      responding baboons maintained on the cholesterol and fat-enriched diet, we
      determined the relative expression of ABCA1, ABCG5, ABCG8, and 27-hydroxylase
      genes in the liver and intestine using TaqMan real-time polymerase chain
      reaction. There was no consistent difference in the expression of ABC
      transporters and 27-hydroxylase in the intestine between high- and low-responding
      baboons. However, hepatic expression of sterol 27-hydroxylase, ABCG5, and ABCG8
      was higher in low-responding baboons than in high-responding baboons. There was
      also a significant correlation between the expression of sterol 27-hydroxylase
      and ABCG5, and ABCG8 in both the liver and the intestine. These results suggest
      that differences in hepatic lipid metabolism but not in cholesterol absorption
      between high- and low-responding baboons observed previously may be mediated by
      the differences in the expression levels of 27-hydroxylase, ABCG5, and ABCG8.

PMID- 15860121
TI  - Assessment of nutritional status in rhesus monkeys: comparison of dual-energy X
      ray absorptiometry and stable isotope dilution.
AB  - Body composition estimates from dual-energy X-ray absorptiometry and stable
      isotope dilution ((2)H and (18)O) were compared in 61 rhesus monkeys (Macaca
      mulatta) from the ongoing long-term energy restriction study at the University of
      Wisconsin. Their average age was 18.9 +/- 2.5 y/o. Of the animals, 51% were in
      the energy restricted group and 38% were females. Although the correlation
      between methods was highly significant for fat mass (R(2) = 0.97, SEE = 0.25 kg
      or 7.5%, P < 0.0001) and fat-free mass (R(2) = 0.98, SEE = 0.29 kg or 3.6%, P <
      0.0001), we observed that dual-energy X-ray absorptiometry underestimated fat
      mass by 0.67 +/- 0.26 kg (7.5%, P < 0.0001) and overestimated fat-free mass by
      0.57 +/- 0.29 kg (20%, P < 0.0001) when compared with isotope dilution. Taken
      together with data from the literature, the present results emphasize the
      usefulness of dual-energy X-ray absorptiometry to derive body composition and
      thus nutritional status in monkeys, but demonstrate the importance of validation
      experiments for a given DXA model and software.

PMID- 15860119
TI  - SIV-specific T lymphocyte responses in PBMC and lymphoid tissues of SIV-infected
      pigtailed macaques during suppressive combination antiretroviral therapy.
AB  - There is currently no SIV macaque model in which the effects of combination
      antiretroviral therapy on tissue immune responses and latent reservoirs have been
      measured. This study was performed to define the impact of combination therapy on
      the specificity and distribution of the T lymphocyte response in multiple tissue
      compartments. Pigtailed macaques (Macaca nemestrina) were infected with SIV/17E
      Fr and treated with combination antiretroviral therapy consisting of 9-R-(2
      phosphonomethoxypropyl)adenine (PMPA) and beta-2',3'-dideoxy-3'-thia-5
      fluorocytidine (FTC). The SIV-specific T lymphocyte response was measured in
      peripheral blood, spleen and several lymph nodes at necropsy by IFN-gamma Elispot
      analysis. Two animals (one treated, one untreated) had high acute peak viremia,
      which was associated with lower SIV-specific T lymphocyte responses in the
      peripheral blood and lymphoid tissues. In the treated animal, viremia was
      controlled to low or undetectable for the study duration, and virus-specific
      responses remained low. The untreated animal remained viremic throughout the
      study and developed clinical symptoms of AIDS. In contrast, the two animals that
      had lower acute peak viremia (one treated, one untreated) had more robust T
      lymphocyte responses, and controlled viral replication. Virus-specific responses
      were detected in the treated animal despite 6 months of suppressive therapy.
      These data suggest that in this model, in the context of acute peak viremia and
      weak T cell responses, combination therapy may be essential to control virus
      replication and disease progression. Conversely, in the setting of low initial
      viremia and robust T lymphocyte responses, treatment does not have a detrimental
      effect on the immune response.

PMID- 15860122
TI  - Cataracts in a laboratory colony of African green monkeys (Chlorocebus aethiops).
AB  - Three cases of spontaneous cataracts were investigated in a colony of African
      green monkeys (Chlorocebus aethiops). Clinical, pathological and microbiological
      investigations were conducted in two cases of juvenile cataracts and in one case
      of a mature cataract. These investigations revealed no indication of an infection
      as the cause of cataract development. A genetic correlation existed between the
      affected individuals. Clinical chemistry gave a hint that calcium might be a "key
      factor" in the development of these cataracts: in both cases of the juvenile
      cataracts, the calcium content in the serum and in the aqueous humor was clearly
      decreased in the affected babies. The calcium uptake in the affected baby itself
      was not altered but the calcium content in the mother's milk was low.

PMID- 15860123
TI  - Hematologic and lymphocyte immunophenotypic reference values for normal rhesus
      monkey (Macaca mulatta) umbilical cord blood; gravidity may play a role in study
      design.
AB  - Hematology and flow cytometry reference values for rhesus umbilical cord blood
      (UCB) were established in 17 healthy infant rhesus monkeys delivered by elective
      cesarean section 10 days preterm. The infants were born to age matched, singly
      caged primigravid or secundigravid dams. The hematology and flow cytometry values
      were determined by automated cell counter and by FACS. No significant differences
      were observed with respect to infant gender. With respect to gravida, the
      primigravid infants had a significantly higher percentage (P= 0.05) of CD20(+) B
      lymphocytes in UCB. These results provide useful reference values for future
      studies of maternal - fetal disease transmission, vaccine and drug evaluation in
      non-human primate pregnancy, as well as fetal programming and immune modulation,
      gene therapy and the use of UCB as a source of stem cells for research and
      transplantation. Importantly, our results suggest that maternal gravidity may be
      an important variable to consider.

PMID- 15860124
TI  - Risks associated with environmental enrichment: intestinal obstruction caused by
      foraging substrate.
AB  - Questions are occasionally asked about the safety of enrichment techniques,
      considering that many novel ways are frequently employed to ensure environmental
      complexity. A juvenile male vervet monkey was found with a phytobezoar of straw
      obstructing the sigmoid colon. The straw was foraging substrate, which is used in
      communal cages. Due to the extent of the resulting necrosis in the sigmoid and
      descending colon, the monkey had to be killed. This is the only individual to
      have suffered a harmful effect from the foraging substrate from amongst 120
      vervet monkeys, which have been permanently housed on straw for over 5 years.

PMID- 15860125
TI  - Comparison between sex and age class on some physiological, thermal, and
      hematological indices of the cerrado's marmoset (Callithrix penicillata).
AB  - There are few papers about physiological indices in Callithrix penicillata, an
      increasing primate model in biomedicine. We investigated levels of plasmatic
      cortisol, plasmatic glucose, free fatty acids, blood cells, tympanic temperature,
      rectal temperature in C. penicllata, under a fast restraint. Measures of body and
      weight were accomplished. Males and females were not different regarding any
      measurements. Body measurements indicated differences between adults and
      juveniles. Adults showed higher hematocrit and a tendency for higher free fatty
      acids than juveniles. Right tympanic temperature was higher in adults than
      juveniles. This result suggests a higher reaction metabolism in adults than
      juveniles under a restraint stress. Due to the short-time of collecting the data,
      plasmatic cortisol did not influence physiological parameters. Therefore, we
      suggest that present results could be considered referential values of C.
      penicillata physiology.

PMID- 15860126
TI  - Quality of life in children newly diagnosed with cancer and their mothers.
AB  - BACKGROUND: With current treatments, approximately 75% of children diagnosed with
      cancer can expect to achieve disease-free survival. However, treatments are
      complex and aggressive, potentially compromising QOL for children and their
      parents. Although previous work has shown increased anxiety and depression among
      parents after diagnosis, the recent development of standardised measures of QOL
      enables us to look more directly at the impact of diagnosis on mothers' and
      children's QOL. The aims of this study are to i) describe QOL for children and
      their mothers after diagnosis by comparing their scores with population norms,
      ii) explore the relationship between mothers' worries about the illness and their
      QOL, and iii) determine the relationship between mothers ratings of their own QOL
      and their child. METHOD: A total of 87 families took part, constituting 60% of
      those eligible. The children included 58 males and 29 females aged between 2
      years 6 months to 16 years 3 months (mean = 7 years, median = 5 years 8 months).
      Diagnoses were acute lymphoblastic leukaemia (ALL, n = 57), brain tumours (n =
      11), bone tumours (n = 17) and 2 rare cancers. Mothers completed questionnaires
      about their own and the child's QOL. RESULTS: Mothers' reported their own and the
      child's QOL to be significantly lower than population norms. There were
      significant correlations between mothers' worries and their own and their ratings
      of the child's QOL and mothers' ratings of their own QOL correlated with their
      ratings of the child's QOL. CONCLUSION: Both children and their mothers
      experience significantly compromised QOL in the months following diagnosis.
      Mothers who rated their own QOL to be poor also rate their child's QOL to be low.
      These results suggest caution is required where mothers rate their child's QOL.
      Efforts must continue to be made to improve QOL of children especially in the
      period immediately following diagnosis.

PMID- 15860127
TI  - Under-reporting of inpatient services utilisation in household surveys -- a
      population-based study in Hong Kong.
AB  - BACKGROUND: Recognising that household interviews may produce biased estimates of
      health services utilisation, we examined for under- and over-reporting of
      hospitalisation episodes in three recent, consecutive population-based household
      surveys in Hong Kong. METHODS: Territory-wide inpatient service utilisation
      volumes as estimated from the 1999, 2001 and 2002 Thematic Household Surveys
      (THS) were benchmarked against corresponding statistics derived from routine
      administrative databases. Between-year differences on net under-reporting were
      quantified by Cohen's d effect size. To assess the potential for systematic
      biases in under-reporting, age- and sex-specific net under-reporting rates within
      each survey year were computed and the F-test was performed to evaluate
      differences between demographic subgroups. We modelled the effects of age and sex
      on the likelihood of ever hospitalisation through logistic regression to compare
      the odds ratios respectively derived from survey and administrative data.
      RESULTS: The extent of net under-reporting was moderately large in all three
      years amounting to about one-third of all inpatient episodes. However, there did
      not appear to be significant systematic biases in the degree of under-reporting
      by age or sex on stratified analyses and logistic regression modelling.
      CONCLUSION: Under-reporting was substantial in Hong Kong's THS. Recall bias was
      likely most responsible for such reporting inaccuracies. A proper full-design
      record-check study should be carried out to confirm the present findings.

PMID- 15860128
TI  - Dietary omega-3 fatty acids and ionizing irradiation on human breast cancer
      xenograft growth and angiogenesis.
AB  - BACKGROUND: The effects of an omega-3 (n-3) fatty acid enriched diet alone and in
      combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA
      MB231 breast cancer xenograft were tested. The cancer cells were injected into
      the mammary fat pad of young female mice. Six weeks later, mice were randomly
      divided into two diet groups: 1) mice with 10% corn oil (rich in omega 6 fatty
      acids) in their food, 2) mice consuming a 10% fat diet that was enriched in n-3
      fatty acids. After two weeks on the diet, treatment with 200 cGy of IR every
      second day for four treatments (total 800 cGy) was initiated on half of the mice
      from each diet group. Some mice in each of the 4 groups were euthanized 24 hours
      after the end of IR while the remaining mice were followed for 3 additional
      weeks. Tumor sections were stained for endothelial cells with CD31 and PAS and
      for hypoxia inducible factor 1alpha (HIF-alpha). RESULTS: The tumor cortex within
      100 microns of the well-vascularized capsule had little vascularization. Blood
      vessels, capillaries, and endothelial pseudopods were found at areas greater than
      100 microns from the capsule (subcortex). Mice on the corn oil diet and treated
      with IR 24 hours previously or non-irradiated mice fed the n-3 diet had tumors
      with fewer blood vessels in the subcortex and more endothelial pseudopods
      projecting into hypoxic (HIF- alpha positive) areas than did mice from the non
      irradiated corn oil fed group. The tumor growth rate of mice that received IR or
      that were fed the n-3 fatty acid enriched diet was significantly slower than in
      the mice fed the 10% corn oil diet. Harmful side effects were found only in the
      IR treated mice. CONCLUSION: The omega-3 fatty acid enriched diet proved to be a
      safe means for retarding tumor growth and vascularization.

PMID- 15860129
TI  - Management of leiomyosarcomas of the spermatic cord: the role of reconstructive
      surgery.
AB  - BACKGROUND: Leiomyosarcomas (LMS) of the spermatic cord are extremely rare.
      Radical inguinal orchiectomy and high ligation of the cord is the standard
      primary surgical procedure. The extent of surrounding soft tissue excision
      required and the precise role of adjuvant radiotherapy, however, remains unclear.
      In addition, recurrence is a commonly encountered problem which might necessitate
      further radical excision of adjacent soft tissues. METHODS: This article reviews
      the pathophysiology of spermatic cord leiomyosarcomas (LMS), and discusses the
      various reconstructive surgical options available to repair the inguinal region
      and the lower anterior abdominal wall after excision of the tumour and the
      adjacent soft tissues. RESULTS: There is paucity of literature on LMS of
      spermatic cord. The majority of paratesticular neoplasms are of mesenchymal
      origin and up to 30% of these are malignant. In adults, approximately 10% of
      spermatic cord sarcomas are LMS. Approximately 50% of these tumours recur loco
      regionally following definitive surgery; however, the incidence decreases if
      resection is followed by adjuvant radiotherapy. CONCLUSION: It is therefore
      important to achieve negative histological margins during the primary surgical
      procedure, even if adjuvant radiotherapy is instituted. If extensive resection is
      required, either during the primary procedure or following recurrence,
      reconstructive surgery may become necessary. This article reviews the
      pathophysiology of spermatic cord LMS, the reasons for recurrence, and discusses
      the management options including the role of reconstructive surgery.

PMID- 15860130
TI  - Clade, Country and Region-specific HIV-1 Vaccines: Are they necessary?
AB  - Today, scientists are often encouraged to custom-design vaccines based on a
      particular country or clade. Here, we review the scientific literature and then
      suggest that the overwhelming endeavor to produce a unique vaccine for every
      world region or virus subtype may not be necessary.

PMID- 15860131
TI  - Central fatigue and nycthemeral change of serum tryptophan and serotonin in the
      athletic horse.
AB  - BACKGROUND: The serotonergic system is associated with numerous brain functions,
      including the resetting of the mammalian circadian clock. The synthesis and
      metabolism of 5-HT in the brain increases in response to exercise and is
      correlated with high levels of blood-borne tryptophan (TRP). The present
      investigation was aimed at testing the existence of a daily rhythm of TRP and 5
      HT in the blood of athletic horses. METHODS: Blood samples from 5 Thoroughbred
      mares were collected at 4-hour intervals for 48 hours (starting at 08:00 hours on
      day 1 and finishing at 4:00 on day 2) via an intravenous cannula inserted into
      the jugular vein. Tryptophan and serotonin concentrations were assessed by HPLC.
      Data analysis was conducted by one-way repeated measures analysis of variance
      (ANOVA) and by the single cosinor method. RESULTS: ANOVA showed a highly
      significant influence of time both on tryptophan and on serotonin, in all horses,
      on either day, with p values < 0.0001. Cosinor analysis identified the periodic
      parameters and their acrophases (expressed in hours) during the 2 days of
      monitoring. Both parameters studied showed evening acrophases. CONCLUSION: The
      results showed that serotonin and tryptophan blood levels undergo nycthemeral
      variation with typical evening acrophases. These results enhance the
      understanding of the athlete horse's chronoperformance and facilitate the
      establishment of training programs that take into account the nycthemeral pattern
      of aminoacids deeply involved in the onset of central fatigue.

PMID- 15860132
TI  - Effects of chronic widespread pain on the health status and quality of life of
      women after breast cancer surgery.
AB  - BACKGROUND: Most research and treatment of post-breast cancer chronic pain has
      focused on local or regional pain problems in the operated area. The purpose of
      this pilot study was to compare and contrast the pain characteristics, symptom
      impact, health status, and quality of life of post-breast cancer surgery women
      with regional chronic pain versus those with widespread chronic pain. METHODS: A
      cross-sectional, descriptive design compared two groups of women with chronic
      pain that began after surgery: regional pain (n = 11) and widespread pain (n =
      12). Demographics, characteristics of the surgery, as well as standardized
      questionnaires that measured pain (Brief Pain Inventory (BPI), Short Form McGill
      Pain Questionnaire (MPQ-SF)), disease impact (Fibromyalgia Impact Questionnaire
      (FIQ), Functional Assessment of Cancer Therapy-Breast (FACT-B)), health status
      (Medical Outcomes Short Form (SF-36)) and quality of life (Quality of Life Scale
      (QOLS)) were gathered. RESULTS: There were no significant differences between the
      groups on any demographic or type of surgery variable. A majority of both groups
      described their pain as aching, tender, and sharp on the MPQ-SF. On the BPI,
      intensity of pain and pain interference were significantly higher in the
      widespread pain group. Differences between the two groups reached statistical
      significance on the FIQ total score as well as the FACT-B physical well-being,
      emotional well-being and breast concerns subscales. The SF-36 physical function,
      physical role, and body pain subscales were significantly lower in the widespread
      pain group. QOLS scores were lower in the widespread pain group, but did not
      reach statistical significance. CONCLUSION: This preliminary work suggests that
      the women in this study who experienced widespread pain after breast cancer
      surgery had significantly more severity of pain, pain impact and lower physical
      health status than those with regional pain.

PMID- 15860133
TI  - Adoptive T cell therapy: Addressing challenges in cancer immunotherapy.
AB  - Adoptive T cell therapy involves the ex vivo selection and expansion of effector
      cells for the treatment of patients with cancer. In this review, the advantages
      and limitations of using antigen-specific T cells are discussed in counterpoint
      to vaccine strategies. Although vaccination strategies represent more readily
      available reagents, adoptive T cell therapy provides highly selected T cells of
      defined phenotype, specificity and function that may influence their biological
      behavior in vivo. Adoptive T cell therapy offers not only translational
      opportunities but also a means to address fundamental issues in the evolving
      field of cancer immunotherapy.

PMID- 15860134
TI  - A novel duplication polymorphism in the FANCA promoter and its association with
      breast and ovarian cancer.
AB  - The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a
      rare autosomal recessive disorder characterised by congenital abnormalities, bone
      marrow failure, and predisposition to malignancy. FANCA is also a potential
      breast and ovarian cancer susceptibility gene. A novel allele was identified
      which has a tandem duplication of a 13 base pair sequence in the promoter region.
      METHODS: We screened germline DNA from 352 breast cancer patients, 390 ovarian
      cancer patients and 256 normal controls to determine if the presence of either of
      these two alleles was associated with an increased risk of breast or ovarian
      cancer. RESULTS: The duplication allele had a frequency of 0.34 in the normal
      controls. There was a non-significant decrease in the frequency of the
      duplication allele in breast cancer patients. The frequency of the duplication
      allele was significantly decreased in ovarian cancer patients. However, when
      malignant and benign tumours were considered separately, the decrease was only
      significant in benign tumours. CONCLUSION: The allele with the tandem duplication
      does not appear to modify breast cancer risk but may act as a low penetrance
      protective allele for ovarian cancer.

PMID- 15860136
TI  - The neurologist and patient safety.
AB  - BACKGROUND: The objective of this article is to acquaint neurologists with the
      current status of evidence and opinion on patient safety in neurology. Research
      data on errors and preventable adverse events (harm from medical management) in
      neurology are sparse, with little light being cast thus far on the
      vulnerabilities of individual neurologists and neurologic office practices.
      However, areas of particular concern and lines of appropriate action are now
      becoming apparent. REVIEW SUMMARY: This review draws on the few studies of
      neurologic malpractice claims, inpatient incident reports and chart reviews, and
      articles and abstracts in the journal literature. These are placed in the context
      of the general epidemiology of medical errors, adverse events, and approaches to
      remediation. CONCLUSION: Accurate and timely diagnosis in all its aspects
      represents the single largest category of error. Most neurologists have their
      first interaction with a patient and family at the time of a critical illness,
      underlining the importance of improved communication, not only with them but with
      other caregivers. Systems of information transfer, such as those enabling timely
      imaging reports, are critical. Better consultative follow-up may be pivotal.
      Education in patient safety competencies and closer supervision of trainees can
      be expected to improve protection. Venues, such as emergency departments, in
      which relevant knowledge and skills may be insufficient to maximize patient
      safety, deserve particular attention.

PMID- 15860137
TI  - Massive cerebral infarction.
AB  - BACKGROUND: Massive cerebral infarcts cause brain edema with midline shifts and
      impingement on vital structures producing coma and death. The mortality rate is
      estimated at 80% with standard medical treatment. Surgical decompression with
      hemicraniectomy has proved to be life saving, but the impact on functional
      outcomes is largely unknown. The focus of this review is to discuss the treatment
      options for massive cerebral infarcts. REVIEW SUMMARY: Neurologic deterioration
      following massive cerebral infarct needs to be recognized early enough for
      medical and surgical interventions. Medical management includes monitoring in a
      neurologic intensive care unit, hyperosmolar agents, and hyperventilation.
      Surgical management includes decompressive hemicraniectomy and duraplasty with
      resection of infarcted tissue in some instances. CONCLUSION: Hemicraniectomy is
      emerging as a promising treatment of patients with massive cerebral infarcts, but
      only select patients benefit from this procedure. Further information from
      randomized controlled trials is required to elucidate the best treatment options
      for this kind of stroke.

PMID- 15860138
TI  - The ketogenic diet.
AB  - BACKGROUND: The ketogenic diet is a low-carbohydrate, adequate-protein, and high
      fat diet with a long history of use for the treatment of intractable seizures in
      children. This dietary therapy has been enjoying increasing popularity in recent
      years, despite the availability of increasing numbers of new antiepileptic drugs
      and surgical treatments. REVIEW SUMMARY: The authors review the history of the
      ketogenic diet, the traditional protocol in initiating it, possible mechanisms of
      its action, evidence for efficacy, and side effects. In addition, they highlight
      some of the areas of active research in this field as well as future directions
      and unanswered questions. CONCLUSION: The ketogenic diet is an efficacious and
      relatively safe treatment of intractable seizures. Despite its long history,
      however, much remains unknown about the diet, including its mechanisms of action,
      the optimal protocol, and the full range of its applicability. Investigations of
      the diet are providing new insight into the mechanisms behind seizures and
      epilepsy itself, as well as possible new therapies.

PMID- 15860139
TI  - Upward transtentorial herniation, hydrocephalus, and cerebellar edema in
      hypertensive encephalopathy.
AB  - BACKGROUND: Edema of the cerebellum with secondary obstructive hydrocephalus is a
      rare presentation of hypertensive encephalopathy. The authors report an unusual
      case of isolated posterior fossa swelling with upward transtentorial herniation
      and hydrocephalus causing neurologic deterioration. These patients are often
      initially evaluated by a neurologist because of the acute neurologic symptoms.
      Prompt diagnosis with aggressive blood pressure control may obviate the need for
      emergent cerebrospinal fluid (CSF) diversion. REVIEW SUMMARY: This is a case
      report of a 26-year-old man who presented to the emergency room with confusion
      and somnolence over a 2-day period. His initial blood pressure was 175/110 mmHg.
      On examination he was disoriented, with a Glasgow Coma Scale score of 12 points,
      opening his eyes only to loud verbal stimuli, verbalizing inappropriately, and he
      was only able to follow simple commands. Neuroimaging revealed edema of the
      cerebellar folia with noncommunicating hydrocephalus and upward transtentorial
      herniation. Differential diagnoses of posterior fossa tumor, rhombencephalitis,
      and hypertensive encephalopathy were entertained. A thorough literature review is
      included with the discussion of this case. The patient underwent emergent
      ventriculostomy for CSF drainage and prompt blood pressure control with
      nitroprusside. After 48 hours of CSF drainage and correction of his hypertension,
      his neurologic examination normalized. Repeat imaging revealed near resolution of
      the obstructive hydrocephalus and cerebellar edema. CONCLUSION: Isolated edema of
      the cerebellum with upward transtentorial herniation and obstructive
      hydrocephalus is a rare presentation of hypertensive encephalopathy and should be
      considered in patients with an acute hypertensive crisis and mental status
      changes. This entity responds to prompt blood pressure control; however, emergent
      ventriculostomy by a neurosurgical team should be entertained for neurologic
      deterioration secondary to significant obstructive hydrocephalus, as illustrated
      in this case.

PMID- 15860140
TI  - Yoga neuropathy. A snoozer.
AB  - Sciatic nerve compression very rarely occurs bilaterally. The authors present a
      woman with profound lower extremity weakness and sensory abnormality after
      falling asleep in the head-to-knees yoga position (also called
      "Paschimottanasana"). Clinical and electrodiagnostic findings are discussed in
      detail and a brief review of the literature is presented.

PMID- 15860141
TI  - Cauda equina and conus medullaris syndrome in sarcoidosis.
AB  - BACKGROUND: Neurosarcoidosis is a rare manifestation of sarcoidosis. Involvement
      of the nervous system in sarcoidosis can range from peripheral or cranial
      neuropathy to central nervous system disease. Cauda equina sarcoidosis is
      distinctly rare. REVIEW SUMMARY: The authors present a 58-year-old patient with
      systemic sarcoidosis who developed cauda equina and conus medullaris syndrome.
      Seventeen previous published cases of cauda equina sarcoidosis are reviewed. The
      history of systemic sarcoidosis, cerebrospinal fluid characteristics of
      lymphocytic pleocytosis with elevated protein, and evidence of acute denervation
      by needle electromyography are helpful in the diagnosis of this condition. Early
      diagnosis and treatment of cauda equina sarcoidosis usually provide a rapid
      recovery and yield a good prognosis. CONCLUSION: Although rare, sarcoidosis
      should be considered in the differential diagnosis of cauda equina syndrome,
      particularly in patients with unclear etiology.

PMID- 15860142
TI  - A sciatic nerve lesion secondary to compression by a heterotopic ossification in
      the hip and thigh region--an electrodiagnostic approach.
AB  - A sciatic nerve lesion secondary to compression by a heterotopic ossification is
      rare. Operative release of the encased sciatic nerve in some cases may restore
      the function of the nerve partially or completely. However, in some cases the
      injury may be permanent. An electrophysiologic study is very useful to determine
      the location and severity of nerve damage, including axonal loss, demyelination,
      or both. An electrophysiologic study can emphasize the portion of the sciatic
      nerve that has been involved the most (lateral versus medial or peroneal versus
      tibial). In some cases an electrophysiologic study can suggest whether surgery
      should be postponed if a recovery pattern from the nerve injury is obvious. The
      prognostic value of follow-up studies is considerable. The authors reviewed
      literature available to them since 1971 and found 6 cases, including their own.
      This is the first attempt to put together all the information available in the
      literature about this condition.

PMID- 15860143
TI  - Herpes simplex encephalitis. Is anticoagulation safe?
AB  - BACKGROUND: Herpes simplex encephalitis (HSE) still carries a high morbidity and
      mortality. REVIEW SUMMARY: The authors report a 27-year-old patient who presented
      with an HSE manifested by a high temperature, seizures, and headaches. His
      hospitalization course was complicated by a pulmonary embolism. After
      anticoagulation was started, the patient developed a right temporal hematoma at
      the same region of the abnormal signal on magnetic resonance imaging. The patient
      underwent a craniotomy and evacuation of the hematoma with an uneventful
      postoperative outcome. CONCLUSION: The safety of anticoagulation in HSE has not
      been raised in the literature previously, and it needs further study.

PMID- 15860144
TI  - 10 questions about using apomorphine for Parkinson disease.

PMID- 15860145
TI  - Benign essential blepharospasm.

PMID- 15860146
TI  - [Our experience with revision total knee arthroplasty].
AB  - PURPOSE OF THE STUDY: In the period from 1990 and June 2003, 885 total knee
      replacements were performed at the orthopedic ward of the Ceske Budejovice
      Hospital. Of these, 19 (2.14 %) patients underwent revision surgery; in addition,
      25 patients who had had primary surgery in other hospitals were operated on. Of
      these 44 patients, 25 were followed up and evaluated. The aim of the study was to
      evaluate the pre-operative treatment including examination for bacterial
      infection by cultivation, the selection of an optimal procedure (one- or two
      stage operation, surgical approach and implantation technique) and postoperative
      therapy. MATERIAL: The 25 evaluated patients were followed up for an average of
      34.5 months (range, 6-109 months) after reimplantation. Loosening occurred in
      most of the commonly used types of primary implants. The group comprised five men
      and 19 women; the average age at the time of reoperation was 70 years (range, 51
      78 years). Ten patients had repeat surgery on the left and 14 on the right knee
      at an average of 43.5 months (range, 4-120 months) after primary surgery.
      Fourteen patients were treated by one-stage and 10 patients by two-stage surgery.
      The Genesis system (Smith Nephew) was used in 13 patients, Sigma PFC revision
      implant (Johnson and Johnson) in eight, Walter-Motorlet implant (reuse of the
      primary implant at the time when a revision system was not available) in one and
      external fixator in five patients. METHODS: Revision arthroplasty was indicated
      on the basis of clinical symptoms and X-ray, scintigraphic and biochemical (CRP,
      WBC, FW) examinations. The use of recently adopted methods (procalcitonin,
      orosomucoid, alpha-1-antitrypsin, beta-2- macroglobulin, ceruloplasmin, PCR and
      PET) was not evaluated because of short-term applications. Patients in whom
      infection or colonization of the implant was suspected were treated by two-stage
      reimplantation, using a canalized spacer with a stem and a patellar pelota made
      of antibiotic-loaded cement. The average time between implant removal and
      reimplantation was 108 days (range, 60-244 days). Each removed implant was placed
      in a culture medium for 5 to 7 days. This resulted in a high occurrence of
      positive cultivation results even in the patients who, on the basis of previous
      examination, were first considered to have had aseptic loosening and had
      undergone one-stage surgery. All patients with positive tests received long-term
      antibiotic therapy, usually a combination of ciprofloxacin and rifampicin,
      according to the cultivation results. RESULTS: Out of 14 one-stage
      reimplantations (indicated for by the negative results of all laboratory
      examinations), implant colonization was recorded in five cases, with a coagulase
      negative staphylococcus being the most frequent infectious agent. No recurrent
      infection was found after the long-term antibiotic course. One patient with the
      implant infected with Staphylococcus aureus underwent primary arthrodesis. Out of
      10 two-stage reimplantations (in patients with positive laboratory tests),
      recurrent infection was found in two cases and was caused by a pathogen different
      from the original one. The patients were treated by arthrodesis. Good outcomes,
      defined as a functional total knee replacement free from infection at least 6
      months after reimplantation, were achieved in 79 % of the patients. Better
      functional results were obtained by onestage surgery. Patients with concomitant
      rheumatoid arthritis had aseptic loosening more frequently, and patients with
      impaired immunological status, due to diabetes mellitus, cytostatic drug or
      corticosteroid administration, more often showed septic loosening. DISCUSSION:
      The 2.14 % loosening of total knee arthroplasty in our patients (19 out of 885)
      can be considered a good result. A functional joint was achieved in all patients
      (100 %) with aseptic loosening and in 69 % of those with infected or colonized
      implants. The results of routine biochemical tests and bacteriological
      cultivation did not allow us to distinguish aseptic from septic loosening with
      certainty. Therefore, we adopted new screening markers (PCR and PET) and a new
      method of microbiological examination of the removed implant and collected
      tissue. However, we could evaluate the role of these specialized tests only on
      the basis of literature data, since we had only short-term experience with them
      ourselves. Our results with the treatment of early loosening of total knee
      arthroplasty suggest that patients benefit more from the two-stage procedure.
      CONCLUSIONS: We strongly emphasize the employment of all possible means to
      prevent loosening, i. e., to use an appropriate surgical technique for primary
      implantation, to observe aseptic principles and to administer antibiotic therapy
      in conditions suspected of bacteremia. The shorter the interval between the onset
      of complaints and the reimplantation, the better results. Early loosening should
      be treated by two-stage surgery. Our method of bacteriological examination gives
      good results. Because of complexity of the problem, patients with a loose knee
      prosthesis should be referred to orthopedic departments with experienced and
      skilled surgical teams and high-quality examination facilities.With the
      observation of appropriate procedures, there is a great chance of achieving good
      results. Arthrodesis is still regarded as a justified "salvage" operation,
      particularly in cases with pre-operative findings of Staphylococcus aureus.
      Procedures for repeat surgery following the failure of a reimplanted joint have
      so far yielded doubtful results and still await further development.

PMID- 15860148
TI  - [Harms technique of C1-C2 fixation with polyaxial screws and rods].
AB  - PURPOSE OF THE STUDY: The Harms technique of stabilizing C1-C2 by fixation with
      polyaxial screws and rods is a further option for atlantoaxial fixation from the
      dorsal approach. Harms and Melcher published this method in 2001, but the
      operation had first been performed by Harms in August 1997. The aim of this study
      is to evaluate the first results and try to assign the Harms C1-C2 fixation an
      appropriate standing in the in broad range of options for stabilization of the
      atlantoaxial complex. MATERIAL: Between December 2002 and January 2004 we carried
      out the Harms fixation of C1-C2 on 22 patients admitted to the Department of
      Spine Surgery, Motol University Hospital, 2nd Medical Faculty in Prague. Out of
      these, 18 patients were included in this study, 10 men and 8 women between 23 and
      84 years of age (average, 55.4 years) followed-up longer than 6 months. In 14
      patients we used the Harms technique as a permanent fixation of C1-C2 in order to
      achieve atlantoaxial arthrodesis and, in four patients, we applied it only for a
      period of 4 to 6 months without the use of bone grafts or their substitutions. We
      employed the permanent fixation to treat the following conditions: fracture of
      the atlas in three patients, type IIA comminuted fracture of the dens base in
      three patients, fracture of C2 categorized as "other" in two patients,
      atlantoaxial vertical instability in one patient with rheumatoid arthritis,
      malunion of the fractured dens in one patient, and complicated trauma to C1-C2 in
      four patients. The temporary fixation was used for type III displaced fractures
      of the dens in two and fixed atlantoaxial rotatory dislocations also in two
      cases. Only one patient showed signs of Frankel C neurological deficit on
      admission, the rest were without neurological findings. METHODS: All screws were
      inserted under an image intensifier always in lateral projection. First we
      retracted the greater occipital nerve in a caudal direction towards C2 with a
      fine raspatory and, using an awl, marked the entry point in the C1 lateral mass;
      a pilot hole, reaching through the anterior cortical bone, was made with a 2.5 mm
      drill. It followed a straight or slightly convergent trajectory in an anterior
      posterior direction and parallel to the plane of the C1 posterior arch in the
      sagittal direction. Individual anatomical variations in the atlantoaxial complex
      of every patient were respected. The hole was tapped through the entire vertebral
      body, with the exception of osteoporous bone in which only the posterior cortical
      bone was treated with a screw tap. At this stage profuse bleeding usually arose
      from dissection around the epidural venous plexus along the C1-C2 joint. This was
      effectively controlled by a quick insertion of a screw and compression of the
      venous plexus with the screw head. To control bleeding by bipolar electrocautery
      is difficult and is always associated with a risk of nerve injury. Screws 3.5 mm
      thick, with polyaxial heads, were inserted bicortically into the lateral mass of
      C1. Subsequently, the intervertebral C2-C3 joint was localized and its medial
      border in the spinal canal was palpated. The entry point for placement of a C2
      pedicle screw was marked with an awl at the point of intersection at a distance
      of 2 mm from the medial border and 5 mm from the caudal border of the C2
      articular process. Under an X-ray intensifier in lateral projection, a hole was
      drilled approximately parallel to the screws inserted in C1, i. e., at an angle
      of 20 to 30 degrees cranially, up to and through the anterior cortical bone. In
      the transversal plane, the screws were situated in a convergent direction at an
      angle of 20 to 25 degrees. After all screws had been inserted, we reduced the
      antlantoaxial complex in the correct anatomical position by manipulating the
      patient's head or by directly adjusting the screws. Connecting 3.0-mm rods were
      then applied and fastened by cap nuts or inner nuts according to the
      instrumentation used. RESULTS: Operative time ranged from 35 to 155 min, with an
      average of 81 min. Intra-operative blood loss ranged from 50 to 1500 ml, with an
      average of 560 ml. The X-ray intensifier was used for a period of 0.4 to 2.6 min,
      with an average of 0.9 min. A total of 36 screws were inserted in the atlas;
      their length ranged from 16 to 34 mm (average, 30.6 mm). All screws were
      positioned correctly in the C1 lateral mass; two screws did not reach up to the
      anterior cortical bone and one protruded over it, but without causing clinical
      problems. Thirty-six screws were inserted in the axis. Their length ranged from
      28 to 36 mm (average, 31.7) mm). Twenty-seven screws were correctly applied
      through the isthmus into the C2 anterior cortical bone, three were too short to
      reach it and five were placed too close to the vertebral artery canal. Of these,
      two protruded into the artery canal, but without clinical consequences. One screw
      inserted too medially passed into the spinal canal, but this also was without
      clinical response. Of the 36 screws inserted in C2, three (8.3 %) were
      malpositioned. Bony fusion at C1-C2 was the goal of this operation in 14
      patients. At 6 weeks post-operatively, it was achieved in two patients, at 12
      weeks in 12 patients and at 6 months in all 14 patients. The C1-C2 segment was
      stable at 12 weeks in all 18 treated patients. Four patients reported restriction
      of motion in rotation by 10 to 25 % after removal of the instrumentation.
      DISCUSSION: Operative time, longer at the beginning than with the Magerl
      technique, gradually shortened to between 45 and 60 min. Similar trends were seen
      when intra-operative blood loss and X-ray exposure were evaluated. Using the
      Harms and Melcher procedure we saved the greater suboccipital nerve. In contrast
      to these authors, however, we did not resect the atlantoaxial joint. Solid fusion
      was achieved in all our patients. Of the total of 72 screws inserted, only three
      (4.2 %) were assessed as malpositioned; however, when related to the 36 screws
      inserted in C2, this was 8.3 %, which indicates that insertion of screws in C2
      was more difficult. We did not observe any clinical consequences in any of these
      cases. CONCLUSIONS: The Harms fixation of C1-C2 is a very effective technique for
      stabilizing the atlantoaxial complex. It enables us to provide temporary fixation
      without damage to atlantoaxial joints and to reduce the vertebrae after the
      screws and rods had been inserted, which is unique. These advantages compensate
      for a higher cost of the implant.

PMID- 15860147
TI  - [Arthroscopy of the hip joint].
AB  - PURPOSE OF THE STUDY: Arthroscopic examination of joints has recently gained wide
      application. Due to hip joint shape and a difficult approach to it, hip
      arthroscopy has long remained outside the attention and abilities of
      arthroscopists. The authors present their first experience with operative hip
      arthroscopy that offers new options for the treatment of intra-articular
      pathology of the hip joint. MATERIAL: In the years 2001-2003, 24 hip
      arthroscopies were performed. The following pathological conditions were
      diagnosed and treated: loose bodies, chondral lesions of the femoral head and
      acetabulum, ruptures of the labrum acetabuli and ligamentum teres, impingement
      syndrome of the labrum acetabuli, and coxitis. No post-operative neurologic
      symptoms or vascular complications were observed. METHODS: All procedures were
      carried out on patients in a supine position, with the treated joint in traction.
      A standard 30 degrees device and common instruments for arthroscopic surgery were
      used. The instruments were inserted in the articular fissure with the use of an X
      ray intensifier. Movement in the hip joint during surgery is very limited due to
      traction, joint shape and the length of working canals. After traction is
      released, it is possible to examine also the intra-articular part of the femoral
      neck. RESULTS: The pre-operative complaints (clunking, painful joint) were
      relieved up to 4 to 6 weeks after surgery in 23 patients. In one patient
      primarily diagnosed with coxitis, infection was not eradicated after lavage and
      debridement and, because inflammation deeply affected the femoral head, the hip
      was eventually treated by Girdlestone arthroplasty. The results were evaluated
      clinically and on the basis of the Merle d'Aubigne and Postel questionnaire
      assessing pain and walking abilities by both the patients and the surgeon. All 24
      patients reported poor or average conditions before surgery and, after surgery,
      23 experienced improvement to a very good or average condition. One patient's
      state failed to improve and was evaluated as poor both before and after surgery.
      DISCUSSION: Hip arthroscopy is a minimal invasive technique which allows us to
      diagnose and, at the same time, treat intra-articular pathology in a gentle
      manner. In arthroscopic surgery, correct diagnosis (X-ray, CT and MRI), correct
      patient's position, their body mass (obesity), selection of appropriate
      approaches to the joint, surgeon's experience and potentials of arthroscopic
      instruments all play an important role. We assume that, with increasing
      experience, the number of patients as well as the scope of diagnosed and treated
      pathological conditions of the hip joint will grow. The outcomes of operative
      arthroscopy were very good (improvement in 23 of 24 patients) and it is probable
      that this technique can slow down or prevent early wear-and-tear hip arthritis.
      CONCLUSIONS: In our country, operative arthroscopy of the hip is only at its
      beginning. However, it can be assumed that, similarly to other large joints, it
      will soon become a widely used, indispensable diagnostic and therapeutic method.

PMID- 15860149
TI  - [Infectious complications after arthroscopic replacement of the cruciate
      ligaments].
AB  - PURPOSE OF THE STUDY: Infection following replacement of the cruciate ligaments
      of the knee joint may result in not only graft failure but also complete
      destruction of the joint. The aim of this study was to report the authors'
      experience with the diagnosis and therapy of this, fortunately occasional,
      complication. MATERIAL: In the period from October 1999 till June 2003, a total
      of 2372 arthroscopic operations of the knee joint were carried out; of these, 908
      were cruciate ligament replacements. Three surgeons using the same technique were
      involved. An autologous graft taken from the ligamentum patellae and fixed with
      interference screws was used in 857 knees, and a graft derived from the tendon of
      the semitendinosus or the gracilis muscle, with "endobutton" fixation, was
      employed. Two kinds of inflammatory complications were recorded in the early post
      operative period, i. e., infection of the articular cavity and infected
      subcutaneous hematoma at site of graft collection. METHODS: When infection of the
      articular cavity was suspected because of severe pain, perspiration, motion
      restriction, articular exudate and increased temperature, arthrocentesis was
      performed and a sample of the fluid withdrawn was sent for cultivation;
      laboratory tests (blood counts, erythrocyte sedimentation rate, C-reactive
      protein) were carried out and antibiotic therapy was started. When there was no
      subsidence of signs within 24 h, revision surgery was carried out without waiting
      for the results of laboratory examination. Coagula from inside of the cavity were
      removed through a short incision on the lateral side of the suprapatellar recess
      and, after repeated thorough irrigation, a suction drain was inserted. Antibiotic
      therapy was administered parenterally. Infected subcutaneous hematoma, associated
      with edema, reddening and tension of the skin, pain, fluctuation and, in some
      cases, high temperature, was treated by disintegration of the wound, removal of
      the hematoma, debridement and thorough irrigation. After drain insertion, the
      wound was closed by suture. The development of infectious complications was
      assessed in relation to the risk factors described in the literature, namely,
      patient's age, operating room time and tourniquet application, previous
      infections of the upper respiratory or urinary tracts, previous surgery on the
      same joint and the season in which the operation was performed. RESULTS: A total
      of 37 revision operations following replacement of the cruciate ligaments of the
      knee joint were carried out; of these, 29 involved the articular cavity. An
      infectious agent was found in six cases (0.7 % of the total number of cruciate
      ligament replacements). Eight knees were treated for hematoma in the wound at
      site of graft collection and, in seven of them, Staphylococcus aureus was
      isolated (0.8 % of the total number of crucial ligament replacements). For
      recurrent problems the distal fixation material had to be removed in two patients
      at 6 and 12 months, respectively. Afterwards the patients were free from
      symptoms. The only risk factor for the development of infection was found to be
      previous surgery on the same joint. DISCUSSION: The authors prefer early revision
      surgery in the cases showing signs of developing infection in the articular
      cavity or hematoma in the wound after graft collection. Therefore the results of
      positive cultivation were fewer in comparison with other relevant reports. In
      revision surgery on the articular cavity, the authors made a 2-cm incision on the
      lateral side of the suprapatellar recess, which enabled them to wash out all
      coagula, in comparison to other authors who recommend irrigation with the use of
      arthroscopic apparatus only. The early intervention made it possible to keep all
      grafts in situ. The only factor associated with a higher occurrence of
      complications in our patients was a previous operation on the same joint.
      CONCLUSIONS: On the basis of their experience with arthroscopic replacement of
      the cruciate ligaments, the authors recommend an active approach if the
      development of infectious complications is suspected. In our patients, no
      persisting sequelae were recorded.

PMID- 15860150
TI  - [Anterior cruciate ligament reconstruction -- long-term results evaluated
      clinically and by means of a rollimeter].
AB  - PURPOSE OF THE STUDY: Anterior cruciate ligament (ACL) reconstruction has
      recently become a widely used method of treating chronic instability. We have
      performed this operation in our department since 1996. The aim of this study was
      to evaluate the effect of this operation in a long-term perspective, using the
      rollimeter, a new device facilitating objective assessment of anterior stability
      of the knee. MATERIAL: Of 150 patients undergoing surgery for lesions of the
      anterior cruciate ligaments at the Department of Orthopedics for Children and
      Adults, 2nd Faculty of Medicine, Charles University and Motol Teaching Hospital,
      in the years 1996-2000, 42 were included in this study. Ligament reconstruction
      was performed by the transtibial technique using B-T-B patellar ligament graft;
      90 % of the patients were treated by arthroscopy, 10 % by open surgery. METHODS:
      The patients operated on between 1996 and 2000 received a questionnaire and were
      invited to undergo examination at our outpatient department. The evaluation was
      based on the IKDC from, the results of Lachman's test performed on the rollimeter
      which permits objective assessment of the test, Tegner scores for assessment of
      daily activities and Lysholm scores for comparison of pre- and post-operative
      values. The results were statistically analyzed. Subjective evaluation was
      obtained from the questionnaires the patients submitted at this examination.
      RESULTS: The results show that, if the appropriate procedure is observed, the
      operation provides a reliable outcome by restoring knee joint stability and
      enabling the patient to return to previous sports activities. The new device
      rollimeter proved effective because of its simple construction and easy
      manipulation, and because the values obtained were more objective than those from
      clinical examination. The treated knee function evaluated on the basis of IKDC
      was normal or almost normal in 86 % of the patients. The objective measurement by
      the rollimeter of the anterior tibial translation showed a difference of up to 5
      mm between the treated and the contralateral extremity. The average activity
      assessed according to Tergner increased by 3 grades and the average Lysholm
      scores improved by 30 points. A difference greater than 5 mm in anterior tibial
      translation between the treated and the contralateral extremity was considered as
      graft failure; this occurred in 7 % of the patients. The drawback of this
      operation, however, remains a restricted ability to kneel comfortably without
      pain and paresthesia in and around the tibial tuberosity. DISCUSSION: The first
      results of objective evaluation of ACL replacement show that a correctly
      performed operation results in a clear improvement in biomechanical properties of
      the knee joint. Our group of patients was evaluated by the established criteria
      and the results are in agreement with those reported in the relevant literature.
      In addition, the purpose of our study was to inform about the use of a new,
      simple measuring device that would be more easily available to hospitals in the
      Czech Republic than the KT 1000 arthrometer of western provenance. Both these
      devices, in contrast to other scoring systems, can provide objective assessment
      of post-operative outcomes and their broader application would contribute to a
      higher quality of retrospective evaluation of patient groups also in other
      hospitals. CONCLUSIONS: Our results are in agreement with those of published
      studies and give support to the fact that ACL reconstruction is a technically
      demanding operation whose results depend on strict observations of the surgical
      procedure and on the frequency of surgery carried out at individual institutions.
      Our study shows the possibility of a broader use of the rollimeter as an
      alternative to the KT 1000 arthrometer commonly used in other countries.

PMID- 15860151
TI  - Prophylaxis of heterotopic bone formation by radiotherapy -- a comparison between
      pre- and postsurgical activity.
AB  - INTRODUCTION: Heterotopic bone formation after total hip replacement is estimated
      to occur in about 30% of all patients. It may develop into restriction of
      mobility and persisting pain. MATERIAL AND METHODS: From 1991 to 1998, 90
      patients with uncemented total hip replacement and known risks to develop
      heterotopic bone formation were treated by radiotherapy (14 patients received 5 x
      3 gy between the first and the fifth postoperative day, 13 patients received 1 x
      7 gy between 24 hours postoperative, 63 Patients received 1 x 7 gy between 24
      hours preoperative) using gamma ray or high-energy photons. The distance between
      radiation and surgical procedure was never more than 24 hours. Clinical and
      radiological assessment was carried out 3, 6 and 12 month after surgery. RESULTS:
      Independent of the method of radiotherapy no clinically relevant ossification was
      noticed on the follow up in any of the 90 patients. CONCLUSION: The results of
      this study show the efficiency of radiotherapy in the prophylaxis of heterotopic
      bone formation, independent of the three applied methods. It seems to be
      important, that the interval between radiation and surgery is not longer than 24
      hours. Because of possible risks and logistic problems preoperative radiation
      should be preferred over postsurgical treatment.

PMID- 15860152
TI  - Radiological changes around the stem after cementless hip implantation in case of
      the anatomic medullary locking hip system -- five years results.
AB  - INTRODUCTION: We present radiological results regarding the development of stress
      shielding around the stem of the AML hip endoprosthesis and discuss the clinical
      significance of it and preventive measures against stress shielding. MATERIAL AND
      METHODS: 391 patients (216 female and 122 male) with an AML-hip-endoprosthesis
      between 1991 and 1992 were followed clinically and radiologically during 5 years
      postoperatively. It was searched for a statistical correlation of stress
      shielding with a pre-existing osteoporosis of the proximal femur (Barnett-Nordin
      index), the diameter of the stem, a varus position of the stem and thigh pain.
      RESULTS: Stress shielding occurred in only 13.5 % of all patients. Atrophy of the
      proximal femur was detectable within 1 year, in 5 cases already after 3 weeks.
      Distal sclerosis reached its maximum after 1-2 years. Remarkably, women showed a
      tendency to more frequent stress shielding. In women more often than in men, a
      pre-existing osteoporosis of the proximal femur occurred. Cases with osteoporosis
      of the proximal femur experienced more often stress shielding. The same was seen
      in prostheses with diameters >13.5 mm. A slight varus position of the stem also
      favoured stress shielding, but it indicated an incomplete canal fit of the stems,
      too. Patients with stress shielding more often were suffered from thigh pain.
      CONCLUSION: Stress shielding is a result of the discrepancy between the
      elasticity of the bony femur and the stiffness of the stem. The AML-hip
      prosthesis rarely shows this phenomenon. An osteoporosis of the proximal femur
      (coupled with an thinning of the cortex and generating higher elasticity of the
      bone), stems with higher diameters (what means higher stiffness) and incomplete
      canal fit more likely predisposed patients to stress shielding. To prevent stress
      shielding, the AML prosthesis should not be implanted in cases with known severe
      osteoporosis of the proximal femur. This prosthesis should be taken preferable in
      cases with diameters of the femoral canal smaller than 15 mm. Fully canal fit has
      to be achieved. The frequency of thigh pain, which occurs more often in patients
      with stress shielding, could be reduced by considering those factors.

PMID- 15860153
TI  - [Partial denervation of the wrist by excision of the interosseous nerves from the
      dorsal approach].
AB  - PURPOSE OF THE STUDY: The aim of the study was to optimize, on the basis of an
      anatomical study, the technique of partial denervation of the wrist in terms of
      safety for preserving motor innervation of the quadrate pronator muscle, and to
      include this technique in the range of reconstruction operations for the
      treatment of degenerative carpal diseases. MATERIAL AND METHODS: The technique of
      partial denervation of the wrist, using excision of the sensitive branches of the
      dorsal and volar interosseous nerves, carried out by one-stage surgery from the
      dorsal approach is presented in a group of 28 patients. The partial denervation
      was always performed in addition to reconstructive surgery on the proximal
      carpals and the distal radioulnar joint. On the basis of an anatomical study
      involving 40 cadaverous upper extremities, the authors determined the location
      for resection of the sensitive branch of the volar interosseous nerve that is not
      associated with the risk of damaged motor innervation of the quadrate pronator
      muscle. RESULTS: A reliable identification of the motor branches of the volar
      interosseous nerve was achieved when an approximately 2-cm incision in the
      interosseous membrane was made 1 cm distal to the passing anterior branch of the
      interosseous artery that was clearly seen in the operating field. This
      corresponded to an incision in the skin, leading in the proximal direction at a
      length of about 7 cm, made 2 cm proximal to the distal radio-ulnar joint.
      DISCUSSION: The identification of motor branches is often difficult and therefore
      the authors recommend resection of the sensitive branch of the volar interosseous
      nerve to be performed in a safe zone that was determined by a large number of
      anatomical dissections. Partial denervation carried out according to the
      principles of a physiological procedure does not pose a burden for the patient
      and can markedly enhance the effect of reconstructive surgery. CONCLUSION:
      Partial denervation of the wrist performed from the dorsal approach is a simple
      procedure easy to combine with other reconstructive operations on the wrist.

PMID- 15860154
TI  - [Treatment of talar chondral lesions by solid chondral graft -- first
      experience].
AB  - The aim of this report is to draw attention to new possibilities of treating
      chondral lesions of the talus, using a solid chondral graft consisting of
      autologous chondrocytes grown on a three-dimensional matrix of the tissue glue
      Tissucol. This method is used in grade II to grade IV chronic lesions and grade
      IV acute lesions, as classified according to the Berndt and Harty system.
      Patients' age at implantation should not exceed 40 years. When a lesion is found
      by arthroscopy on the talar dome, a part of cartilage from a non-weight-bearing
      surface, most frequently the neck of the talus or the anterior edge of the tibia,
      is collected. The cartilage is sent to the tissue bank. The preparation of a
      chondral graft (fragmentation, isolation and cultivation of chondrocytes) takes
      from 15 to 35 days. After shaping the graft from chondrocytes and Tissucol tissue
      glue in a special mould, transplantation is carried out. In 2003 we used this
      method in two patients. They both were male sportsmen, football players, aged 35
      and 30 years, respectively. At the time of this report, the former patient was 8
      months and the latter 3 months after implantation. The first patient, aged 35,
      was without complaints at 8 months after implantation. The other patient, a 30
      year-old football player, who was still followed up, was without complaints and
      continued with rehabilitation and full weight-bearing of the extremity. Magnetic
      resonance imaging performed 3 months post-operatively showed good incorporation
      of the chondral graft in both patients.

PMID- 15860155
TI  - The European school of total hip arthroplasty and 35 years of total hip
      arthroplasty in the Czech Republic.
AB  - The development of the European total hip arthroplasty in the sixties of 20th
      century is associated mainly with the names of G. K. McKee, J. Charnley and M. E.
      Muller. The SICOT meeting in Paris in 1966 introduced THA as a new method of
      treatment of osteoarthritis of the hip and paved the way for the
      commercialization of the manufacturing of prostheses. The success of this method
      consisted primarily in the fixation of individual components by bone cement and
      application of metal-to-polyethylene and metal-to-metal joints. The book presents
      these historical events as they have been reflected in the development of THA in
      the countries of the former Czechoslovakia and in the development of implants of
      domestic provenance. The development of THA in the former Czechoslovakia started
      in 1969 and was based on the Swiss school established by M. E. Muller. The Muller
      component with the "banana-shaped" stem was implanted using the Watson-Jones
      approach, the proximal femur canal was prepared by a rasp and the Palacos cement
      was used. This prosthesis served also as the model for the first Czech implant
      Poldi-Cech of I generation (the Chirulen cup available in three sizes, the
      "banana- shaped" femoral component with a 32 mm head-diameter and 130 degree neck
      shaft angle) the development of which started in 1969 and the serial production
      began in 1972 in the Poldi Kladno steel company. Fatigue fractures of the "banana
      shaped" stem led to the development of the concept of a femoral component with an
      "anatomical" stem. In Switzerland, this concept was developed by B. G. Weber. In
      the former Czechoslovakia the development of a new femoral component with an
      "anatomical" stem following the shape of the intramedullary canal with an ovoid
      profile and without sharp edges started in 1972. Due to the incidence of fatigue
      fractures of the "banana-shaped"stem and material that was not sufficiently
      strong (steel used for the production of osteosynthetic components), 144 degree
      neck-shaft angle was chosen. Reduction of the effect of bending forces on the
      valgus stem had eliminated fatigue fractures. This Poldi-Cech prosthesis of II
      generation was provided in nine sizes. The diameter of the head remained the
      same. Three Chirulen cups were supplemented with a "flat" cup for implantation in
      a dysplastic acetabulum. The prosthesis was implanted with an exact instrument
      set (reamer for acetabular preparation, rasp for proximal femoral preparation,
      alignment device for accurate positioning of both the cup and the femoral
      component) with the use of the Palacos cement. The production of the Poldi-Cech
      prosthesis of II. generation started in 1974 with the fabrication of a monoblock.
      Since 1986 it has been developed into a modular system (14/16 cone) with the
      possibility to use a ceramic head of 32 mm diameter (only in the nineties the
      cone size was changed to 12/14 and the heads were provided also in the 28 mm
      diameter). The Poldi-Cech prosthesis of II generation with the "anatomical" stem
      has been implanted since 1974 (i. e. during 30 years) in more than 140 000
      patients in the Czech and Slovak Republics. In the same year cemented monoblock
      hemiarthroplasty was developed on the same basis as THA using the same
      "anatomical" stem and 36 to 60mm head diameter. Until now more than 35,000 of
      these hemiarthroplasty systems have been implanted. Until 1992 the Poldi-Cech
      implant was practically the only available cemented total hip replacement in the
      former Czechoslovakia and retrospectively it may be considered a highly
      successful implant. In the authors' view, the further development of THA will
      lead in the following years to the use of implants proved by a long-term follow
      up. Preference will be given to prostheses the implantation of which will require
      a minimal loss of the bone stock during primary surgery and which will allow a
      technically easy reimplantation. The continental Europe has been recently
      preferring hybrid prostheses while Scandinavia witnesses an evident increase in
      the number of implanted cemented prostheses to the detriment of the cementless
      and hybrid ones. Naturally, cementless prostheses will keep dominating in young
      patients.

PMID- 15860156
TI  - [Reflections on measuring health-related quality of life in Spain].

PMID- 15860157
TI  - [Development of the Spanish version of the KIDSCREEN, a health-related quality of
      life instrument for children and adolescents].
AB  - AIMS: To describe the cross-cultural development and psychometric properties of
      the Spanish version of the KIDSCREEN questionnaire, a health related quality of
      life instrument (HRQL) for use in children and adolescents aged 8-18 years old.
      The questionnaire was cross-culturally developed in 13 European countries.
      METHODS: A literature review and Delphi study were performed, allowing consensus
      to be reached on the instrument's contents and structure. More specific items and
      dimensions were generated in focus groups. Forward and back translation and
      cultural adaptation were carried out, together with a pre-test (cognitive
      debriefing) to select items that were acceptable in all the countries involved. A
      pilot study was performed to obtain the definitive version of the KIDSCREEN
      through Rasch analysis and preliminary information on the questionnaire's
      psychometric properties. RESULTS: The focus groups generated 1642 possible items,
      which were reduced during the stages of translation-adaptation and pilot study.
      The definitive version of the questionnaire contains 52 items and 10 dimensions.
      In the Spanish version, there was less than 5% nonequivalence (acceptability) in
      any of the dimensions, floor and ceiling effects were acceptable, and all
      dimensions had Cronbach's alpha values of > 0.70 (internal consistency).
      CONCLUSIONS: The KIDSCREEN is the first HRQL instrument for children and
      adolescents to be developed simultaneously in several countries. The preliminary
      psychometric properties of the Spanish version were acceptable.

PMID- 15860158
TI  - [Design and validation of a questionnaire for the detection of major depression
      in elderly patients].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to design and validate a
      scale to detect major depressive disorders in elderly individuals in primary care
      (Detection of Depression in the Elderly Scale [DDES]). METHODS: We performed an
      observational and cross-sectional study for the validation of a scale,
      administered by means of a personal interview, in 259 patients aged 65 years old
      or older. Available instruments were reviewed and the questions were designed.
      Subsequently, a first pilot study was performed. In a second pilot study the
      reproducibility of the instrument was analyzed. The gold standard was the result
      of a standardized psychiatric interview performed by psychiatrists (DSM-IV
      criteria and SCAN interviews). RESULTS: The intraclass correlation coefficients
      corresponding to the test-retest and inter-rater reliability were 0.858 (95%
      confidence interval [CI], 0.634-0.946) and 0.908 (95% CI, 0.726-0.969)
      respectively. Two hundred sixteen subjects underwent an assessment, in which
      primary care and psychiatric evaluations were blinded. Major depression was
      diagnosed in 81 patients (37.5%; 95% CI, 31.1-44.4). The internal consistency of
      the DDES was good (Cronbach's alpha = 0.79). Exploratory factorial analysis
      revealed an 8-component structure (55.8% of explained variance). A cutoff score
      of 15 or more for the DDES showed sensitivity of 90.1% (95% CI, 80.95-95.33),
      specificity of 74.8% (95% CI, 66.48-81.71) and a likelihood ratio (+) of 3.58
      (95% CI, 2.65-4.83). CONCLUSIONS: The DDES is a clinically useful instrument for
      the detection of major depression in elderly patients in primary care.

PMID- 15860159
TI  - Factors related to dental health in 12-year-old children: a cross-sectional study
      in pupils.
AB  - OBJECTIVE: The aim of this study was to identify factors related to the
      prevalence of caries in 12-year-old schoolchildren. METHODS: A cross-sectional
      study was carried out using a representative sample (n = 1217) of the population
      of 12-year-old schoolchildren in Galiza (northwest Spain). Independent variables
      were measured through a questionnaire, and dependent variables were determined
      through oral examination. Multiple and logistic regression were applied. RESULTS:
      The decayed, missing and filled permanent teeth/decayed, filled primary teeth
      (DMFT-dft) value in the sample was 1.83 (95% confidence interval [CI], 1.67
      1.98), the DMFT value was 1.53 (95% CI, 1.37-1.67), and the prevalence of caries
      was 61% (95% CI, 57.7-64.5). The prevalence of caries was directly related to a
      low frequency of brushing, greater use of toothpaste, and a higher consumption of
      sweets. The prevalence of caries was higher in rural than in urban areas. In
      contrast, the higher the mother's level of education and the greater the
      subject's knowledge of dental health, the lower the prevalence of caries.
      CONCLUSIONS: The main goals of dental health programmes should be to achieve
      quality brushing every day in children, to reduce the consumption of sweets, and
      to increase knowledge of dental health.

PMID- 15860160
TI  - [Organization, functioning and expectations of organizations representing
      patients. Survey of key informants].
AB  - OBJECTIVES: To explore patient organizations and their scope in terms of patient
      and user participation in decisions affecting their health. METHODS: Semi
      structured questionnaire survey of key informants from 21 patient organizations.
      RESULTS: Most of the patient organizations were regional or national private
      organizations. Their main objectives include improving quality of life and
      representing the interests of patients and their families, developing information
      triage and dissemination activities, and providing additional services not
      offered by the public health service. The main methods of communicating with
      members were electronic mail, open meetings and forums. Most patient
      organizations considered health professionals to be the most important group of
      stakeholders. The sources of funding most frequently quoted were membership fees,
      public grants and contributions from the pharmaceutical industry. The most
      important factor for enhancing patient co-responsibility was considered to be
      involving patients in health care as a way to improve the quality of the heath
      services. The proposed future scenario that received the most support was the
      creation of a legal forum in which the patient's voice could be heard and
      demonstrably taken into account. CONCLUSIONS: Patient organizations can play an
      important role in providing patients and health professionals with information,
      promoting self care and improving the effectiveness of health care. These
      features require visible commitment by the health authorities to facilitate
      opportunities for patient decisions and choice within the system.

PMID- 15860161
TI  - [Variables related to job satisfaction. Cross-sectional study using the European
      Foundation for Quality Management [EFQM] model].
AB  - OBJECTIVES: To identify the influence of the dimensions of people items and
      sociodemographic characteristics included in the EFQM model on high satisfaction
      of healthcare workers in a district hospital. METHODS: We performed a cross
      sectional study in November 2003. The questionnaire used was the personal
      satisfaction survey of the Basque Country (Spain). The outcome measure was a high
      degree of satisfaction (75th percentile or higher). Independent variables were
      sociodemographic and organizational characteristics. The association among
      variables was assessed using odds ratios (OR) and their 95% confidence interval
      (CI). Adjustment for confounders was performed by unconditional logistic
      regression. RESULTS: On a scale from 0 to 10, the mean general satisfaction score
      was 5.95 (standard deviation, 2). Twenty-five percent of workers gave their
      general satisfaction with the organizational climate a score of 8 or more points.
      The most positively considered features were the environmental policy,
      hierarchical relations, promotion, and professional development. The most
      negatively viewed items were salary, knowledge and identification of objectives,
      and training. The variables most closely related to outcome were a favorable
      perception of training (adjusted OR = 5.04; 95% CI, 2.16-11.77) and recognition
      of the work performed (adjusted OR = 4.68; 95% CI, 2.20-10.08). Sociodemographic
      factors had less influence on satisfaction. CONCLUSIONS: Almost half of the staff
      surveyed in our hospital were satisfied or highly satisfied with the
      organizational climate. Satisfaction was strongly associated with positive
      evaluation of organizational characteristics.

PMID- 15860162
TI  - [The Spanish version of the Short Form 36 Health Survey: a decade of experience
      and new developments].
AB  - OBJECTIVE: The Short Form-36 Health Survey (SF-36) is one of the most widely used
      and evaluated generic health-related quality of life (HRQL) questionnaires. After
      almost a decade of use in Spain, the present article critically reviews the
      content and metric properties of the Spanish version, as well as its new
      developments. METHODS: A review of indexed articles that used the Spanish version
      of the SF-36 was performed in Medline (PubMed), the Spanish bibliographic
      databases IBECS and IME. Articles that provided information on the measurement
      model, reliability, validity, and responsiveness to change of the instrument were
      selected. RESULTS: Seventy-nine articles were found, of which 17 evaluated the
      metric characteristics of the questionnaire. The reliability of the SF-36 scales
      was higher than the suggested standard (Cronbach's alpha) of 0.7 in 96% of the
      evaluations. Grouped evaluations obtained by meta-analysis were higher than 0.7
      in all cases. The SF-36 showed good discrimination among severity groups,
      moderate correlations with clinical indicators, and high correlations with other
      HRQL instruments. Moreover, questionnaire scores predicted mortality and were
      able to detect improvement due to therapeutic interventions such as coronary
      angioplasty, benign prostatic hyperplasia surgery, and non-invasive positive
      pressure home ventilation. The new developments (norm-based scoring, version 2,
      the SF-12 and SF-8) improved both the metric properties and interpretation of the
      questionnaire. CONCLUSIONS: The Spanish version of the SF-36 and its recently
      developed versions is a suitable instrument for use in medical research, as well
      as in clinical practice.

PMID- 15860163
TI  - [Drugs in the European Union: the health-market complex].
AB  - OBJECTIVES: To characterize the peculiar economic nature of the pharmaceutical
      market in the EU, to study potential groupings of countries based on several
      pharmaceutical variables, to analyze some recent regulations designed to create
      the single market, and to present some thoughts on the decision making process in
      public health from the perspective of current public health budgets. METHOD: We
      performed an economic analysis of health and pharmaceutical macrovariables,
      cluster analysis, review of EU pharmaceutical and industrial regulations and
      review of pharmaceutical budgeting legislation in the member states. RESULTS: The
      pharmaceutical market of the EU was characterized and EU countries were
      classified into two principal groups according to 5 selected variables. EU
      regulations tend to promote R + D and drug production and thus the EU industrial
      sector is backed up. National regulations differ in terms of pricing and drugs
      reimbursement. CONCLUSIONS: The creation of a single market for drugs in the EU
      should take this regulatory diversity into account and seek equilibrium between
      economic factors and public health. This single market may be a dangerous
      strategy if it becomes a general dogma and even more so if deadlines are fixed
      and short.

PMID- 15860164
TI  - [Singularization processes: a proposal for continuity between clinical activity
      and health policy objectives].
AB  - BACKGROUNDS AND OBJECTIVES: In 1996 the Gipuzkoa Territorial Health Agency
      (Basque Country, Spain) created the Health Plan Service. The aim was to transform
      the health objectives prioritized by the Health Department into intervention
      strategies to be incorporated into the local contract services. PROCESS AND
      RESULTS: One of the procedures the service uses for this purpose, known as
      <<singularization>>, involves selecting a process linked to a prioritized health
      problem, and analyzing and reconstructing it so that the related activity,
      expected results, financial costs and its impact on the population's health can
      be identified. After this process the service provides the Territorial Health
      Agency, which is responsible for service purchase for the public and private
      sectors, with information about contract conditions for the process reviewed.
      Annual assessment of contract services monitors the extent to which the
      agreements made have been carried out and their consequences on the population's
      health. The present article deals with the process through which this
      <<singularization>> is carried out.

PMID- 15860165
TI  - [Opportunities for the 112 Emergency Service to collaborate in public health
      surveillance].
AB  - The Andalusian Regional Ministry of Health is implementing an Alert Integrated
      System (SIA) in order to improve the health protection of the population by means
      of the appropriate response to the sanitary alerts. <<Emergencias 112 Andalucia>>
      is a service aimed both to catastrophic situations and to the other ones needing
      intervention and multisectorial coordination. Theses functions make possible
      their collaboration with the SIA, furnishing it with information about a series
      of environmental incidents. A study has been carried out in order to characterize
      the information received and to evaluate it systematic inclusion in the SIA,
      which include alerts from january to August 2003. The number of incidents
      communicated to 112 were 656, rank between months from 45 to 117. It is
      appropriate to underline the frequency of incidences related to Natural Hazards
      (50.15%) and Environmental Pollution (26.07%). The 67.55% of incidences happened
      between 15.00 p.m. and 8.00 a.m. hours of the following day. By provinces,
      Sevilla reported 24.5%, and the higher rate belongs to Huelva with 4.74
      incidences/100 000 inhabitants. Incidents related to health care, environmental
      problems, risks to alimentary and occupational health, and epidemiological alerts
      are of great interest to the SIA; that is why it is necessary to consider the
      integration of the information systems of the emergency centres in the Public
      Health Surveillance.

PMID- 15860167
TI  - [Functional outcome after one year follow-up in cryptogenetic brain infarction
      and patent foramen ovale].
AB  - BACKGROUND AND OBJECTIVE: The presence of patent foramen ovale (PFO) and
      atrioseptal aneurysm (ASA)has been described as a risk factor in cryptogenetic
      stroke. Patients with unknown origin stroke and PFO have less severe symptoms
      compared to the rest of cryptogenetic stroke patients. We evaluated the clinical
      situation in stroke patients with PFO and describe the factors predictive of a
      better outcome after a year. PATIENTS AND METHOD: 1118 patients between 18 and 70
      years old were evaluated, and 223 were classified as having cryptogenetic stroke.
      Our protocol Included transcranial Doppler, a transesophageal echocardiography
      (TEE) and a cranial RM. We used the NIH Stroke Scale (NIHSS) to evaluate the
      clinical situation, and the modified Ranking Scale for the functional outcome.
      RESULTS: A total of 117 patients had all inclusion criteria. 66 (56.4%) showed a
      PFO. We observed a younger age, a higher percentage of females (48.4% in PFO vs.
      25.5% in no-PFO) and less risk factors in PFO patients, except for migraine
      (24.6% in PFO vs. 5.9% in no-PFO; p = 0.01). PFO patients had less severe strokes
      (NIHSS: 3--median--in PFO vs. 5 in no-PFO; p = 0.010) and a lower grade of
      sequelae (p 0.024). Worse outcome was related to male, initial neurological
      evaluation (NIHSS) and presence of ASA. After a logistic regression, only the
      initial clinical situation (NIHSS) and the presence of ASA were associated with
      sequelae. CONCLUSIONS: PFO patients showed a less severe stroke and better
      functional outcome. The initial neurological involvement and the presence of ASA
      are predictive of the clinical situation after a year.

PMID- 15860168
TI  - [Hemosiderin-laden macrophages count in sputum in diagnosis of dyspnea of heart
      origin].
AB  - BACKGROUND AND OBJECTIVE: The respiratory or heart origin of dyspnea is not
      always easy to find out using the available diagnostic tools. Many patients
      present both heart and lung diseases that cause dyspnea. The role of hemosiderin
      laden macrophages count (HC) in sputum in this context has not been well settled
      so far. The objective was to describe the prediction usefulness of HC in patients
      suffering from dyspnea of heart origin, and to find out if HC changed after
      administering treatment. PATIENTS AND METHOD: HC was analyzed in 61 patients
      whose main symptom was dyspnea in the emergency department, and it was evaluated
      by means of clinical history, clinical course and performance of lung function
      tests and echocardiography. RESULTS: 35 patients were classified as having
      dyspnea of heart origin, 17 as having dyspnea of lung origin and 9 had dyspnea of
      both origins. The HC was higher in patients with dyspnea of heart origin 37% (95%
      CI, 26-47) or cardiopulmonary origin 30% (95% CI, 8-52) than in patients with
      dyspnea of lung origin 15% (95% CI, 4-27), and it remained higher despite
      administering treatment. The sensitivity (52%), specificity (88%), positive
      predictive value (92%) and negative predictive value (58%) was established for a
      30% HC cutoff. The prediction model of heart origin dyspnea presented an area
      under the ROC curve of 0.978 (95% CI, 0.95-1). CONCLUSIONS: HC reflects the
      severity of pulmonary venocapillar disturbance, identifies the majority of
      patients suffering from current or past heart failure or severe cardiac
      dysfunction, and is useful for the prediction of dyspnea of heart origin. HC
      utility should focus on selected patients.

PMID- 15860169
TI  - [Anorexia nervosa and cerebral atrophy in adolescents].
AB  - BACKGROUND AND OBJECTIVE: The incidence of cerebral atrophy in patients with
      anorexia nervosa and its relation to nutritional parameters has not been
      considered yet. PATIENTS AND METHOD: The medical records of 55 patients were
      reviewed. 47 of them underwent a cerebral magnetic resonance, anthropometric and
      nutritional study. RESULTS: Cerebral atrophy was found in 10 (21.2%) out of the
      47 patients studied. Those patients with cerebral atrophy showed an older age and
      greater percentage of weight loss than patients without atrophy (p = 0.014 and p
      = 0.001) but lower triceps skinfold average (p = 0.001). CONCLUSIONS: Cerebral
      atrophy is common in patients with anorexia nervosa, mainly in those with a
      severe weight loss and lower body fat.

PMID- 15860170
TI  - Surgical (close lateral internal sphincterotomy) versus chemical (botulinum
      toxin) sphincterotomy as treatment of chronic anal fissure.
AB  - BACKGROUND AND OBJECTIVE: The aim of this prospective randomized trial was to
      compare the effectiveness and morbidity of surgical vs chemical sphincterotomy in
      the treatment of chronic anal fissure after a 3-year follow-up period. PATIENTS
      AND METHOD: Eighty patients with chronic anal fissure were treated either with
      close lateral internal sphincterotomy (group 1) or with chemical sphincterotomy
      with 25 U botulinum toxin injected into the internal sphincter (group 2).
      RESULTS: Overall healing was 90% in the close sphincterotomy group and 45% in the
      toxin botulinum group (p < 0.001). There was a group of patients with clinical
      factors (duration of disease over 12 months and presence of a sentinel pile
      before treatment) associated with a higher recurrence of anal fissure. Final
      percentage of incontinence was 5% in the close sphincterotomy group and 0% in the
      botulinum toxin group (p > 0.05). All incontinent patients were aged more than 50
      years. CONCLUSIONS: We recommend surgical sphincterotomy as the first therapeutic
      approach in patients with clinical factors of recurrence. However, we recommend
      the use of botulinum toxin in patients older than 50 years or with associated
      risk factors of incontinence, despite the higher rate of recurrence, since it
      avoids the greater risk of incontinence seen with surgery.

PMID- 15860171
TI  - [Hemosiderophages in respiratory secretions. Biological significance and clinical
      utility].

PMID- 15860172
TI  - [The brain in the patient with anorexia nervosa].

PMID- 15860173
TI  - [Ethics in health decisions].

PMID- 15860174
TI  - [Hereditary hemorrhagic telangiectasia].
AB  - Hereditary Hemorrhagic Telangiectasia (HHT) or Rendu-Osler-Weber disease is a
      genetic disorder with a dominant autosomic transmission. Its prevalence is
      estimated in one in 5-8,000 individuals. Two different mutations have been
      described involving endoglin and ALK-1 genes, resulting in HHT type 1 and 2
      respectively. It is characterized by the occurrence of spontaneous and recurrent
      episodes of epistaxis, telangiectasias and the presence of visceral arteriovenous
      malformations (mainly affecting lungs, liver, brain and digestive tract) which
      are responsible for the clinical manifestations and constitute a basic point in
      the diagnostic criteria of Curacao. The aim of this article is to review the
      pathogenesis, clinical aspects, screening procedures to disclose the visceral
      involvement and the therapeutic options of this rare disease.

PMID- 15860175
TI  - [Abdominal pain and rectorrhage in a 68-year-old woman].

PMID- 15860177
TI  - [Circadian rhythm in acute coronary syndrome].

PMID- 15860178
TI  - [Ecstasy: is it innocuous?].

PMID- 15860179
TI  - [Bazex syndrome, polymyalgia rheumatica or shoulder girdle syndrome?].

PMID- 15860180
TI  - [Mycoplasma pneumoniae pneumonia and pulmonary thromboembolism].

PMID- 15860181
TI  - [Partial androgen insensitivity syndrome associated with familiar breast cancer].

PMID- 15860182
TI  - [Arterial ischemia as first manifestation of multiple venous thromboembolism].

PMID- 15860184
TI  - [What further data are required to extend the use of beta blockers in cardiac
      failure?].

PMID- 15860185
TI  - [Congestive heart failure in Spain: cost-effectiveness and cost-benefit analyses
      of treatment with beta-blockers].
AB  - OBJECTIVE: Beta-blockers (BB) have proven to be effective in the treatment of
      congestive heart failure (CHF). This study is an economic analysis for the
      addition of BB to standard treatment of CHF. PATIENTS AND METHOD: Randomized,
      double-blinded controlled studies are included, with 1,647 patients treated with
      bisoprolol, 3,034 treated with carvedilol, 2,432 treated with metoprolol, and
      6,807 treated with placebo. Direct costs of BB treatment and of every
      hospitalization episode are assessed. Cost-effectiveness is assessed as cost in
      euros by prevented death, and cost-benefit as the difference between
      hospitalization costs and BB costs. The study is conducted from the perspective
      of a third-party payer. RESULTS: Two studies with bisoprolol, six with
      carvedilol, and five with metoprolol are included, with an average follow-up of
      13.5 months. Carvedilol prevents 5.07% of deaths per year of treatment and is
      more effective than bisoprolol (3.82% of avoided deaths) and metoprolol (3.03%).
      Cost-effectiveness ratio (cost for every prevented death and year) was 10,832
      euros for bisoprolol, 17,516 euros for carvedilol and 16,664 euros for
      metoprolol. Incremental cost-effectiveness ratio for carvedilol ranges between
      12,631 euros and 86,610 euros for life saved. All BB generate costs saving for
      hospitalization but only bisoprolol provides a net profit. Benefit-cost index is
      1.13 for bisoprolol, 0.26 for carvedilol and 0.59 for metoprolol. CONCLUSIONS:
      Use of BB in the treatment of CHF is an effective and cost-effective alternative.
      Carvedilol is the most effective alternative, and bisoprolol the most cost
      effective alternative and the drug with greater benefit-cost index.

PMID- 15860186
TI  - [Pain in Spanish rheumatology outpatient offices: EPIDOR epidemiological study].
AB  - OBJECTIVE: To establish the prevalence and characteristics of rheumatologic pain
      in Spanish adult population cared in specialized rheumatology offices. DESIGN:
      Cross selection study in a population of patients cared in rheumatology offices
      of public Spanish hospitals. SUBJECTS: 1,134 patients selected through random
      sampling based on waiting lists of patients, during a period of 1 week, in
      rheumatology offices of each participating hospital. MAIN OUTCOMES OF THE STUDY:
      Reason behind the consultation (a new patient [NP] or a patient for revision
      [RP]), characteristics of the patient (sex, age, habits [alcohol/tobacco],
      marital status), location, type, intensity, duration, tolerance and management of
      pain; treatment (pharmacological or non-pharmacological) carried out;
      satisfaction with the treatment; and association with fibromyalgia. RESULTS: The
      prevalence of pain in NP was 98.6% and in RP 95.1%, with a global prevalence of
      96%, predominating mainly in adult sedentary women with fibromyalgia. The
      frequency of acute pain was 20.9% and this of chronic pain 79.1% [corrected] The
      prevalence of fibromyalgia was 12% (2.2% in men, and 15.5% in women). The most
      prevalent pattern of current dominant pain was this of the mechanical type. More
      frequent associated pathologies were: hypertension (21.7%), depression (14.4%),
      gastrointestinal diseases (13.8%) and anxiety (13.4%). All variables analyzed in
      the study showed changes according to age, sex, and type of patient (NP or RP).
      Most used treatment was pharmacological; more than 57.6% of patients were
      receiving NSAIDs. In NP, medical prescriber of the treatment was first the
      general practitioner (56.1%) followed by the rheumatologist (14.1%); in PR the
      first one was the rheumatologist (69.9%) followed by the general practitioner
      (16.5%). CONCLUSIONS: Our results show that the prevalence of the rheumatologic
      pain is very high, predominating mainly in adult women with fibromyalgia. Pain
      location, intensity, and type, associated pathology, and treatment vary according
      to age, sex, and type of patient. The most commonly used drugs for pain
      management were NSAIDs (58%); opiodes were only used in 6.4% of patients even
      though pain was intense in more than two-thirds.

PMID- 15860187
TI  - [Unknown etiology cardiac tamponade. Could some characteristics of the disease
      define higher probability of specific etiologies?].
AB  - INTRODUCTION: Cardiac tamponade without definite cause (one of the forms of
      primary pericardial disease), always puts the clinician on the alert for the
      possibility of a specific etiology of disease. PATIENTS AND METHODS: The
      objectives of this prospective study on 50 patients with primary pericardial
      disease and cardiac tamponade have been to establish the real incidence of
      specific etiologies in our environment, as well as the principal clinical
      manifestations of these patients. All patients were evaluated through an
      exhaustive diagnostic protocol (including non-invasive diagnostic tests, analysis
      of the pericardial fluid and in some cases pericardial biopsy) for the search of
      a specific cardiac tamponade etiology. RESULTS: In our experience it has been
      most frequent to find a definite etiology in a slightly superior proportion
      (54%), without differences among the idiopathic and specific forms of cardiac
      tamponade with regard to the most relevant clinical manifestations, including the
      aspect and amount of the pericardial fluid and the recurrences of cardiac
      tamponade. CONCLUSIONS: The disease has no clinical manifestations that establish
      its etiology: this justifies in-depth etiological research in this group of
      patients.

PMID- 15860188
TI  - [Pharmacological treatment of osteoarthritis. Expectations and reality].
AB  - In order to assess agent with modulating properties of the course of the
      arthrosic condition, the so-called SYSADOA (Symptomatic Slow Acting Drugs for
      Osteoarthritis) and "structure modifiers" have been defined. Glucosamine sulfate,
      chrondroitin sulfate and diacerein have been considered among these agents. Based
      on the published data and according to the evidence available, the SYSADOA have
      symptomatic effects and can modify the structure. However, although there is
      scientific evidence for the use of these drugs in arthrosis treatment, the
      limited intensity of their action over the placebo makes it necessary to evaluate
      the clinical relevance of their application before recommending their generalized
      use.

PMID- 15860189
TI  - [Asymptomatic bacteriuria in patients with diabetes mellitus. To treat or not to
      treat?].
AB  - Women with diabetes mellitus suffer symptomatic bacteriuria and symptomatic
      urinary infections more often than non-diabetic women. Prevalence is similar,
      however, in males with and without diabetes. There is a controversy on the impact
      of asymptomatic bacteriuria on the development of complications in diabetic
      patients. Current evidence is reviewed concerning the need for detection and
      treatment of asymptomatic bacteriuria in these patients.

PMID- 15860190
TI  - [Obesity pharmacological treatment].
AB  - In this clinical observation, we make a small summary of the current state of
      pharmacological treatment of obesity. The interest in the use of drugs in the
      treatment of obesity has grown in recent years, upon our knowledge of the
      biological basis of obesity having increased, and also because non
      pharmacological treatments have not succeeded stopping the constant increase of
      obesity incidence in western countries. Only two drugs are currently approved by
      the European Agency of the Drug and the FDA (Food and Drug Administration, United
      States) for the treatment of long-term obesity: sibutramine and orlistat.
      Pharmacological treatment of obesity should be considered in obese patients (BMI
      > 30) or overweight (BMI > 27) in presence of comorbidities as diabetes mellitus,
      hypertension, dyslipemias (7.8); this must not be used as an isolated treatment
      but together with other basic therapies: diet, physical exercise and
      psychological support.

PMID- 15860191
TI  - [Gene therapy: current situation and expectations].
AB  - In this review the current situation of gene therapy is described in
      hematological diseases, immunological conditions, and cancer. In all of them, the
      principal objective of various approaches with gene therapy is transduction of
      therapeutic genes in most of target cells. In chronic or immunological diseases,
      a stable expression of therapeutic genes is also required; in tumor cells, the
      efficiency or percentage of transduced cells make conditional on the treatment
      success. Consequently, vectors are one of the basic elements to optimize gene
      therapy approaches and protocols in view of the facts that we know that with
      liposomes less than 10% of cells are transduced, that retrovirus only infect
      cells in replication, and that adenovirus give rise to an important inflammatory
      response and a transitory transduction of the therapeutic gene. In addition
      recent approaches in cancer gene therapy with selective replication virus,
      suicidal genes, etc., are discussed.

PMID- 15860192
TI  - [Dyspnea in a patient sent by the pneumonologist].

PMID- 15860193
TI  - [Complex oculomotor paresis: a sum of fractions].

PMID- 15860194
TI  - [Abdominal pain, dysphagia, and ophthalmoparesis].

PMID- 15860195
TI  - [Renal infarction, cerebral infarction and Leiden factor V].

PMID- 15860196
TI  - [Bone Hodgkin lymphoma: two patients and literature review].

PMID- 15860197
TI  - [Trousseau's syndrome and antithrombin-III deficiency].

PMID- 15860198
TI  - [Characteristics of the outcome of patients reported in three spanish Internal
      Medicine journals].

PMID- 15860199
TI  - Electrospinning of chitosan dissolved in concentrated acetic acid solution.
AB  - Chitosan nanofibers were electrospun from aqueous chitosan solution using
      concentrated acetic acid solution as a solvent. A uniform nanofibrous mat of
      average fiber diameter of 130 nm was obtained from the following optimum
      condition: 7% chitosan solution in aqueous 90% acetic acid solution was
      successfully electrospun in the electric field of 4 kV/cm. The aqueous acetic
      acid concentration higher than 30% was prerequisite for chitosan nanofiber
      formation, because more concentrated acetic acid in water progressively decreased
      surface tension of the chitosan solution and concomitantly increased charge
      density of jet without significant effect on solution viscosity. However, acetic
      acid solution more than 90% did not dissolve enough chitosan to make spinnable
      viscous concentration. Only chitosan of a molecular weight of 106,000 g/mol
      produced bead-free chitosan nanofibers, while low- or high-molecular-weight
      chitosans of 30,000 and 398,000 g/mol did not. Average fiber diameters and size
      distribution decreased with increasing electric field and more bead defects
      appeared at 5 kV/cm or more.

PMID- 15860200
TI  - Synergistic platelet integrin signaling and factor XII activation in poly-N
      acetyl glucosamine fiber-mediated hemostasis.
AB  - The polymer poly-N-acetylglucosamine (pGlcNAc) containing fiber material is
      becoming increasingly important as a topical agent for hemostasis at wound sites.
      The pGlcNAc polymeric fiber provides hemostasis through redundant mechanisms that
      include platelet activation for fibrin network formation. The research presented
      here better defines the mechanism for the effect of pGlcNAc containing fibers on
      platelet-mediated processes. Adsorption experiments demonstrated that pGlcNAc
      fibers tightly bind most major plasma proteins and a specific sub-set of platelet
      surface proteins, including the integrin beta(3) subunit (CD61) and the von
      Willebrand receptor GP1b (CD42b). The result of this interaction is a platelet
      dependent acceleration of fibrin gel formation. Accelerated fibrin polymerization
      is sensitive to factor XII inhibition by corn trypsin inhibitor and integrin
      inactivation with integrilin. Confocal microscopy studies show that when platelet
      integrins contact plasma protein-saturated pGlcNAc fibers, an increase in
      intracellular free calcium for platelet activation occurs to drive surface
      expression of phosphatidyl serine (PS). Thus, a catalytic surface for thrombin
      generation and accelerated fibrin clot formation results from the interaction of
      platelets with pGlcNAc. These findings, when considered with the observation that
      pGlcNAc fibers also induce red blood cell agglutination and vasoconstriction,
      provides an explanation for the ability of the pGlcNAc material to provide
      hemostasis in a wide variety of clinical applications.

PMID- 15860201
TI  - In vivo bone regeneration with injectable calcium phosphate biomaterial: a three
      dimensional micro-computed tomographic, biomechanical and SEM study.
AB  - This in vivo study investigated the efficiency of an injectable calcium phosphate
      bone substitute (IBS) for bone regenerative procedures through non-destructive
      three-dimensional (3D) micro-tomographic (microCT) imaging, biomechanical testing
      with a non-destructive micro-indentation technique and 2D scanning electron
      microscopy (SEM) analysis. The injectable biomaterial was obtained by mixing a
      biphasic calcium phosphate (BCP) ceramic mineral phase and a cellulosic polymer.
      The BCP particles were 200-500 microm or 80-200 microm in diameter. The
      injectable material was implanted for 6 weeks into critical-sized bone defects at
      the distal end of rabbit femurs. Extensive new bone apposition was noted with
      both 2D and 3D techniques. Micro-CT showed that newly formed bone was in perfect
      continuity with the trabecular host bone structure and demonstrated the high
      interconnectivity of the restored bone network. For both IBS formulations, SEM
      and microCT gave very close measurements. The only detected significant
      difference concerned the amount of newly formed bone obtained with IBS 80-200
      that appeared significantly higher with microCT analysis than with SEM
      (p=0.00007). Student t-tests did not show any significant difference in the
      amount of newly formed bone and remaining ceramic obtained from microCT analysis
      or SEM. Regression analysis showed satisfactory correlation between both the
      amount of newly formed bone and remaining ceramic obtained from microCT or SEM.
      For IBS 200-500, the newly formed bone rate inside the defect was 28.0+/-5.2%
      with SEM and yield strength of the samples was 18.8+/-5.4 MPa. For IBS 80-200,
      the newly formed bone rate inside the defect was 31.7+/-5.1% with SEM and yield
      strength of the samples was 26.8+/-4.5 MPa. Yield strength appeared well
      correlated with the amount of newly formed bone, specially observed with microCT.
      This study showed the ability of non-destructive techniques to investigate
      biological and mechanical aspects of bone replacement with injectable
      biomaterials.

PMID- 15860202
TI  - Biocompatibility analysis of poly(glycerol sebacate) as a nerve guide material.
AB  - No satisfactory method currently exists for bridging neural defects. Autografts
      lead to inadequate functional recovery, and most available artificial neural
      conduits possess unfavorable swelling and pro-inflammatory characteristics. This
      study examined the biocompatibility of a novel biodegradable elastomer,
      poly(glycerol sebacate) (PGS), for neural reconstruction applications, as the
      material possesses favorable mechanical property and degradation characteristics.
      The effect of PGS on Schwann cell metabolic activity, attachment, proliferation,
      and apoptosis were examined in vitro in comparison with poly(lactide-co
      glycolide) (PLGA), a biomaterial widely utilized for tissue engineering
      applications. The in vivo tissue response to PGS was compared with PLGA implanted
      juxtaposed to the sciatic nerve; the physical changes in the implant material
      were measured during the degradation process. PGS had no deleterious effect on
      Schwann cell metabolic activity, attachment, or proliferation, and did not induce
      apoptosis; the in vitro effects of PGS were similar to or superior to that of
      PLGA. In vivo, PGS demonstrated a favorable tissue response profile compared with
      PLGA, with significantly less inflammation and fibrosis and without detectable
      swelling during degradation. PGS is an excellent candidate material for neural
      reconstruction applications given its lack of in vitro Schwann cell toxicity and
      minimal in vivo tissue response.

PMID- 15860203
TI  - Bioactivity of titanium following sodium plasma immersion ion implantation and
      deposition.
AB  - Bio-activation of titanium surface by Na plasma immersion ion implantation and
      deposition (PIII and D) is illustrated by precipitation of calcium phosphate and
      cell culture. The bioactivity of the plasma-implanted titanium is compared to
      that of the untreated, Na beam-line implanted and NaOH-treated titanium samples.
      Our data show that the samples can be classified into two groups: non-bioactive
      (untreated titanium and beam-line Na implanted titanium) and bioactive (Na-PIII
      and D and NaOH-treated titanium). None of the four types of surfaces exhibited
      major cell toxicity as determined by lactate dehydrogenase (LDH) release.
      However, the LDH release was higher on the more bioactive PIII and NaOH-treated
      surfaces. From a morphological point of view, cell adherence on the NaOH-treated
      titanium is the best. On the other hand, the cell activity and protein production
      were higher on the non-bioactive surfaces. The high alkaline phosphatase activity
      per cell suggests that the active surfaces support an osteogenic differentiation
      of the bone marrow cells at the expense of lower proliferation. The use of Na
      PIII and D provides an environmentally cleaner technology to improve the
      bioactivity of Ti compared to conventional wet chemical processes. The technique
      is also particularly useful for the uniform and conforming treatment of medical
      implants that typically possess an irregular shape and are difficult to treat by
      conventional ion beam techniques.

PMID- 15860204
TI  - Porosity of 3D biomaterial scaffolds and osteogenesis.
AB  - Porosity and pore size of biomaterial scaffolds play a critical role in bone
      formation in vitro and in vivo. This review explores the state of knowledge
      regarding the relationship between porosity and pore size of biomaterials used
      for bone regeneration. The effect of these morphological features on osteogenesis
      in vitro and in vivo, as well as relationships to mechanical properties of the
      scaffolds, are addressed. In vitro, lower porosity stimulates osteogenesis by
      suppressing cell proliferation and forcing cell aggregation. In contrast, in
      vivo, higher porosity and pore size result in greater bone ingrowth, a conclusion
      that is supported by the absence of reports that show enhanced osteogenic
      outcomes for scaffolds with low void volumes. However, this trend results in
      diminished mechanical properties, thereby setting an upper functional limit for
      pore size and porosity. Thus, a balance must be reached depending on the repair,
      rate of remodeling and rate of degradation of the scaffold material. Based on
      early studies, the minimum requirement for pore size is considered to be
      approximately 100 microm due to cell size, migration requirements and transport.
      However, pore sizes >300 microm are recommended, due to enhanced new bone
      formation and the formation of capillaries. Because of vascularization, pore size
      has been shown to affect the progression of osteogenesis. Small pores favored
      hypoxic conditions and induced osteochondral formation before osteogenesis, while
      large pores, that are well-vascularized, lead to direct osteogenesis (without
      preceding cartilage formation). Gradients in pore sizes are recommended for
      future studies focused on the formation of multiple tissues and tissue
      interfaces. New fabrication techniques, such as solid-free form fabrication, can
      potentially be used to generate scaffolds with morphological and mechanical
      properties more selectively designed to meet the specificity of bone-repair
      needs.

PMID- 15860205
TI  - Cellular response to zinc-containing organoapatite: an in vitro study of
      proliferation, alkaline phosphatase activity and biomineralization.
AB  - We present a series of experiments investigating the in vitro biological activity
      of zinc-containing organoapatite (ZnOA)-coated titanium meshes. ZnOA is a
      hydroxyapatite-based material that contains poly(l-lysine) and zinc ions and can
      be coated onto titanium by treating the metal surface with poly(amino acids) that
      allow for electrostatic bonding of the mineral to the titanium surface.
      Preosteoblastic mouse calyaria cells were cultured on ZnOA-coated titanium meshes
      in a three-dimensional (3D) bioreactor, which provides an in vitro culture
      environment that better simulates what cells experience in vivo, compared to
      traditional 2D cultures. Results of these studies show a time-dependent cascade
      of events leading to an earlier onset of alkaline phosphatase (ALP) expression
      and biomineralization of ZnOA-coated samples as compared to controls. After the
      observation of peak ALP levels in ZnOA-coated titanium samples, mineralized bone
      nodules were observed by scanning electron microscopy. Tetracycline staining
      confirmed that the observed mineral nodules were newly synthesized biomineral,
      and not due to the inorganic coating. ZnOA-coated titanium substrates represent a
      new class of materials for human repair that provide, mechanical stability, as
      well as chemical and biochemical signals to promote new bone growth.

PMID- 15860206
TI  - Characterization of chitosan-polycaprolactone blends for tissue engineering
      applications.
AB  - The objective of this work was to study the effect of blending chitosan with
      poly(epsilon-caprolactone) (PCL) on their biomechanical properties. After testing
      the effect of molecular weight (MW), temperature, and humidity on the tensile
      properties in dry, wet at 25 degrees C and wet at 37 degrees C conditions,
      chitosan with a MW>310 kD was selected for use in the blend. Homogeneous blends
      of 25%, 50% and 75% PCL compositions were formed by dissolving chitosan and 80 kD
      PCL in a common solvent of approximately 77% aqueous acetic acid. Taking
      advantage of the low melting point of PCL, blend membranes were processed at 25,
      37, 55 degrees C water bath or 55 degrees C oven into films. Also, membranes were
      solvent annealed using chloroform vapors. Tensile properties were analyzed in wet
      conditions at 25 degrees C. Support for cell viability and distribution of
      cytoskeletal actin were analyzed by in vitro cell culture of mouse embryonic
      fibroblasts (MEFs). Differential scanning calorimetry studies indicated the
      miscibility of the two components when approximated using Nishi-Wang equation.
      Drying the films at 55 degrees C in an oven formed membranes without separation
      of two phases. However, the analyzed tensile properties showed no significant
      alterations relative to chitosan. On the contrary, significant improvements were
      observed after solvent annealing. Interestingly, increased viability and
      redistribution of actin fibers was observed on blends formed with 50% PCL and 75%
      PCL relative to individual polymers. In summary, 50:50 blends when processed at
      55 degrees C in an oven showed significant improvement in mechanical properties
      as well as support for cellular activity relative to chitosan.

PMID- 15860207
TI  - Three-dimensional culture and differentiation of human osteogenic cells in an
      injectable hydroxypropylmethylcellulose hydrogel.
AB  - The present work evaluates a newly developed silated hydroxypropylmethylcellulose
      (Si-HPMC)-based hydrogel as a scaffold for 3D culture of osteogenic cells. The pH
      variation at room temperature catalyzes the reticulation and self-hardening of
      the viscous polymer solution into a gelatine state. We designed reticulation
      time, final consistency and pH in order to obtain an easy handling matrice,
      suitable for in vitro culture and in vivo injection. Three human osteogenic cell
      lines and normal human osteogenic (HOST) cells were cultured in 3D inside this Si
      HPMC hydrogel. We show here that osteosarcoma cells proliferate as clonogenic
      spheroids and that HOST colonies survive for at least 3 weeks. Mineralization
      assay and gene expression analysis of osteoblastic markers and cytokines,
      indicate that all the cells cultured in 3D into this hydrogel, exhibited a more
      mature differentiation status than cells cultured in monolayer on plastic. This
      study demonstrates that this Si-HPMC hydrogel is well suited to support
      osteoblastic survival, proliferation and differentiation when used as a new
      scaffold for 3D culture and represents also a potential basis for an innovative
      bone repair material.

PMID- 15860208
TI  - Analytically derived material properties of multilaminated extracellular matrix
      devices using the ball-burst test.
AB  - Xenogeneic extracellular matrices (ECMs) have been shown to be effective as
      naturally occurring scaffolds for soft-tissue repair. As acellular tissue
      substitutes at the time of surgical implantation, ECMs are subjected to the
      mechanical forces and micro-environmental conditions representative of the
      anatomical location in which they are placed. Ideally such natural scaffolds
      would possess mechanical properties that allow for normal tissue function in and
      around the implant site. The ball-burst test was used to simulate biaxial forces
      and to determine the strength of the ECM scaffold under a relevant physiological
      loading condition. The ball-burst test, in itself, does not quantify intrinsic
      mechanical properties and therefore a methodology was developed to determine the
      maximum stress resultant tangent modulus (MSRTM) or the maximum stress tangent
      modulus (MSTM), stress to failure (sigma(f)), failure stress resultant (N(f)),
      ball-burst pressure (P), and maximum elongation (lambda(max)) from the raw ball
      burst data obtained at a constant-rate of transverse. The analytical methodology
      was compared to finite element simulations and showed good correlation with the
      analytical solution presented. The proposed approximations were used to compute
      biaxial failure properties for a variety of multilaminate ECM devices with
      varying number of layers, disinfection and sterilization, and organ origin.

PMID- 15860209
TI  - Damage accumulation, fatigue and creep behaviour of vacuum mixed bone cement.
AB  - The behaviour of bone cement under fatigue loading is of interest to assess the
      long-term in vivo performance. In this study, uniaxial tensile fatigue tests were
      performed on CMW-1 bone cement. Acoustic emission sensors and an extensometer
      were attached to monitor damage accumulation and creep deformation respectively.
      The S-N data exhibited the scatter synonymous with bone cement fatigue, with
      large pores generally responsible for premature failure; at 20 MPa specimens
      failed between 2 x 10(3) and 2 x 10(4) load cycles, while at 7 MPa specimens
      failed from 3 x 10(5) load cycles but others were still intact after 3 x 10(6)
      load cycles. Acoustic emission data revealed a non-linear accumulation of damage
      with respect to time, with increasing non-linearity at higher stress levels. The
      damage accumulation process was not continuous, but occurred in bursts separated
      by periods of inactivity. Damage in the specimen was located by acoustic
      emissions, and allowed the failure site to be predicted. Acoustic emission data
      were also used to predict when failure was not imminent. When this was the case
      at 3 million load cycles, the tests were terminated. Creep strain was plotted
      against the number of load cycles and a linear relationship was found when a
      double logarithmic scale was employed. This is the first time a brand of cement
      has been characterised in such detail, i.e. fatigue life, creep and damage
      accumulation. Results are presented in a manner that allows direct comparison
      with published data for other cements. The data can also be used to characterise
      CMW-1 in computational simulations of the damage accumulation process. Further
      evidence is provided for the condition-monitoring capabilities of the acoustic
      emission technique in orthopaedic applications.

PMID- 15860210
TI  - The complete process of bioresorption and bone replacement using devices made of
      forged composites of raw hydroxyapatite particles/poly l-lactide (F-u-HA/PLLA).
AB  - Here we document the complete process of bioresorption and bone replacement of
      rods made of forged composites of unsintered hydroxyapatite particles/poly l
      lactide (F-u-HA/PLLA) implanted in the femoral medullary cavities of rabbits.
      Bioresorption, osteoconductive bioactivity and bone replacement were compared in
      three implantation sites. In the first site, the end of the rod was located near
      the endosteum in the proximal medullary cavity. In the second, the rod was
      located at the centre of the bone marrow space without contacting the endosteum.
      In the third, the rod was in direct contact with cancellous bone within the
      distal femoral condyle. Micro-computerised tomography, scanning electron
      microscopy and photomicrographs of stained sections were used to document the
      complete process of bioresorption and bone replacement. At the first implantation
      site, the rod was completely resorbed and unbound u-HA particles were detected in
      and around the endosteum 5-6 years after implantation. At the second site, the
      rod showed significant shrinkage 4-5 years after implantation due to the release
      of almost all the PLLA, although a contracted cylindrical structure containing a
      few u-HA persisted even after approximately 6 years. At the third site, u-HA
      particles were almost completely replaced with bone after 5-6 years. Conversely,
      PLLA-only rods showed little bone conduction, and small amounts of degraded PLLA
      debris and intervening some tissue persisted even after long periods. Namely, the
      u-HA/PLLA composites were replaced with bone in the distal femoral condyle, where
      they were in direct contact with the bone and new bone formation was anatomically
      necessary. By contrast, composite rods were resorbed without replacement in the
      proximal medullary cavity, in which new bone growth was not required. We
      therefore conclude that the F-u-HA30/40 composites containing 30 wt%/40 wt% u-HA
      particles are clinically effective for use in high-strength bioactive,
      bioresorbable bone-fixation devices with the capacity for total bone replacement.

PMID- 15860211
TI  - The inhibition of neutrophil antibacterial activity by ultra-high molecular
      weight polyethylene particles.
AB  - Following infection, bacterial killing by polymorphonuclear leukocytes
      (neutrophils) is the main host defense against bacteria. Our hypothesis is that
      particles of ultra-high molecular weight polyethylene (UHMWP) may impair local
      neutrophil function and consequently reduce neutrophil bacterial killing. To
      determine how the in vitro phagocytic-bactericidal activity of neutrophils was
      affected by exposure to wear particles, tests were run comparing the effects of
      different particle composition, and different concentrations and sizes of UHMWP
      particles. There was a significant correlation between the number of particles
      and the decrease in neutrophil bactericidal activity (p<0.01), and the greatest
      effect was obtained with a concentration of 10(7) UHMWP/ml. There was a
      significant decrease in neutrophil bactericidal activity by incubation with
      particles of 0.1-5 microm (p<0.01), but not with larger size. The results suggest
      that neutrophil functional defects triggered by the presence of UHMWP particles
      may potentially contribute to the susceptibility of loose implants to bacterial
      infections.

PMID- 15860212
TI  - DNA strands robed with ionic liquid moiety.
AB  - An ionic liquid domain was successfully prepared outside double-stranded DNA by
      fixing 1-alkyl-3-methyl-imidazolium (C(n)MI) cations on the phosphate groups of
      DNA. First, four species of ionic liquid were made using phosphoric acid di-n
      butyl ester and C(n)MI (n=2,4,8, and 12) as a low molecular weight model. They
      were obtained as liquid salts, and their ionic conductivity ranged up to 10(
      5)Scm(-1) at 50 degrees C. Based on this model study, counter cations of the
      phosphate groups of DNA were exchanged for four kinds of imidazolium cations. The
      resulting ionic liquid-robed DNA (IL-robed DNA) was soluble in ordinary organic
      solvents such as methanol or ethanol. Ionic conductivity was low, because the ion
      density was insufficient to form a continuous ionic liquid domain around the DNA
      strands. When 11mol% 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIBF(4)),
      which is a typical ionic liquid, was mixed with the IL-robed DNA, an ionic
      conductivity of 5.4 x 10(-5) S cm(-1) at 30 degrees C was observed because a
      continuous ionic liquid domain was successfully formed.

PMID- 15860213
TI  - A method for the molecular imprinting of hemoglobin on silica surfaces using
      silanes.
AB  - A new molecular imprinting technique using covalently immobilized hemoglobin (Hb)
      is described for creating Hb-specific recognition cavities on silica. Two kinds
      of organic silane (3-aminopropyltrimethoxysilane: APTMS, and
      trimethoxypropylsilane: TMPS) were polymerized on a surface of porous silica
      after the Hb template was covalently immobilized by forming imine bonds, and
      their influence was analyzed. The results showed that not only the silane amount
      but also the relative proportions play an important role in protein imprinting.
      Pore size distribution on Hb imprinted silica was determined by nitrogen
      adsorption/desorption after removing the template Hb. The Hb-imprinted silica
      using covalently immobilized Hb (MIPi) as a template proved superior to silica
      using free Hb (MIPf) regarding displacement of template Hb, and selective re
      adsorption as compared with other non-template proteins. The results suggested
      the capacity for selective adsorption of MIPi to be not only based on the
      isoelectric point (pI) and protein molecular weight, but also the characteristics
      of protein recognition cavities imprinted on base silica.

PMID- 15860214
TI  - Cell microarrays on photochemically modified polytetrafluoroethylene.
AB  - We studied the adhesion, proliferation, and viability of human umbilical vein
      endothelial cells (HUVEC) and human embryonic kidney cells (HEK) on modified
      spots at polytetrafluoroethylene (PTFE) surfaces. The viability of the cells was
      assessed using an aqueous non-radioactive cell proliferation assay. Round spots
      with a diameter of 100 microm were modified by exposure to the ultraviolet (UV)
      light of a Xe(2)(*)-excimer lamp at a wavelength of 172 nm in an ammonia
      atmosphere employing a contact mask. The spots were arranged in a quadratic
      pattern with 300 microm center-to-center spot distances. With optimized degree of
      modification, the cells adhered to the modified spots with a high degree of
      selectivity (70-90%). The adhered cells on the spots proliferated. This resulted
      in a significant increase in the number of adhering HUVECS or HEK cells after
      seeding and in the formation of confluent cell clusters after 3-4 days. With
      higher start seeding density, these clusters were not only confined to the
      modified spots but extended several micrometer to the neighborhood. The high
      potential of the cell microarrays for gene analysis in living cells was
      demonstrated with HEK cells transfected by yellow fluorescent protein (YFP).

PMID- 15860215
TI  - Diffusion in three-dimensionally ordered scaffolds with inverted colloidal
      crystal geometry.
AB  - Inverted colloidal crystal geometry has been recently utilized in the design of
      highly organized 3D cell scaffolds. The regularity of the resulting scaffolds
      enables computational modeling of scaffold properties. In this work we probe the
      resistance offered by these scaffolds to nutrient transport, by using Brownian
      dynamics and Monte Carlo simulations to model the effective nutrient diffusivity.
      Brownian dynamics simulations indicate that the effective diffusivity for small
      nutrients in the scaffold, D(eff)=0.3D(0), where D(0) is the free solution
      diffusivity. Further, results of Monte Carlo simulations for dilute solutions of
      larger particles show that the D(eff) decreases linearly with the size of the
      particles.

PMID- 15860216
TI  - Mycobacterium tuberculosis 6 kDa early secreted antigenic target stimulates
      activation of J774 macrophages.
AB  - The influence of the 6 kDa early-secreted antigenic target (ESAT-6) of
      Mycobacterium tuberculosis on macrophage activation was investigated using J774
      macrophage cell line. While without effect if applied alone, ESAT-6 in a dose
      dependent manner enhanced nitric oxide (NO) release by IFN-gamma-stimulated J774
      cells. However, it completely failed to modulate NO production in J774 cells
      activated with E. coli lipopolysaccharide. The effect of ESAT-6 on NO synthesis
      in IFN-gamma-activated J774 cells was accompanied by up-regulated expression of
      inducible NO synthase (iNOS), an enzyme that catalyzes NO formation. ESAT-6
      mediated enhancement of macrophage NO release was markedly suppressed by
      pharmacological agents that selectively inhibit iNOS enzymatic activity or
      protein tyrosine kinase and mitogen-activated protein kinase activation. Finally,
      treatment of J774 macrophages with ESAT-6 also enhanced IFN-gamma-induced
      expression of the surface molecules B7.1, MHC-II, and ICAM-1. Collectively, these
      data suggest that ESAT-6 might contribute to macrophage activation in
      tuberculosis.

PMID- 15860217
TI  - Interleukin-17 enhances bFGF-, HGF- and VEGF-induced growth of vascular
      endothelial cells.
AB  - Interleukin-17 (IL-17) is a CD4 T cell-derived proinflammatry and proangiogenic
      cytokine. In this study, we investigated the effects of this cytokine on vascular
      endothelial cell growth induced by a well-known direct angiogenic factor bFGF,
      HGF, VEGF, CXCL5/ENA-78 or CXCL8/IL-8. While a wide range of doses of IL-17 alone
      did not show the ability to stimulate the growth of human dermal microvascular
      endothelial cells (HMVECs), bFGF, HGF, VEGF, CXCL5 or CXCL8 significantly induced
      the growth of HMVECs in vitro. When bFGF and IL-17 were used in combination, 10
      or 100 ng/ml IL-17 enhanced 10 ng/ml bFGF-induced growth of HMVECs. Similarly,
      when HGF and IL-17 were combined together, 10 or 100 ng/ml IL-17 potentiated 10
      ng/ml HGF-induced growth of HMVECs. When VEGF and IL-17 were used together, 10
      ng/ml IL-17 did not significantly enhance 10 ng/ml VEGF-induced growth, whereas
      100 ng/ml IL-17 clearly promoted 10ng/ml VEGF-mediated proliferation of HMVECs.
      On the contrary, IL-17 did not augment CXCL5- and CXCL8-mediated growth. These
      results indicate that IL-17 itself does not have the capability to stimulate the
      growth of vascular endothelial cells, whereas IL-17 is able to selectively
      enhance the mitogenic activity of bFGF, HGF, and VEGF for vascular endothelial
      cells. Our findings also suggest that IL-17 may promote bFGF-, HGF- and VEGF
      mediated angiogenesis through enhancing bFGF-, HGF- and VEGF-induced growth of
      vascular endothelial cells.

PMID- 15860218
TI  - FK506 suppresses the stimulation of matrix metalloproteinase 13 synthesis by
      interleukin-1beta in rheumatoid synovial fibroblasts.
AB  - The aim of this study was to determine whether FK506, which has been shown to be
      effective for the treatment of refractory RA, affects the synthesis of matrix
      metalloproteinases (MMPs) in rheumatoid synovial fibroblasts. Synovial
      fibroblasts isolated from rheumatoid synovium were incubated in 6-well culture
      plates for 24 h with FK506 and interleukin-1beta, alone and in combination.
      Samples of supernatants were assayed by ELISA or immunoblottings using anti-MMP
      13 specific antibodies. In addition, synovial fibroblasts pretreated with FK506
      were stimulated with IL-1beta for 10 min and cellular lysates were subjected to
      anti-phospho-specific mitogen-activated protein kinase (MAPK). Unstimulated
      synovial fibroblasts produced low levels of MMP-3 and 13. IL-1beta-induced
      substantial output of these MMPs into cell supernatants. FK506 had no detectable
      effects on IL-1beta-induced MMP-2 induction. FK506, however, significantly
      suppressed MMP-13 production from IL-1beta-stimulated synovial fibroblasts. FK506
      also prevented IL-1beta-stimulated JNK activation and transcriptional activation
      of AP-1 in these cells. Our results indicate that FK506 is capable of regulating
      MMP-13 synthesis via JNK pathway in rheumatoid synonvium.

PMID- 15860219
TI  - Murine TLR2 expression analysis and systemic antagonism by usage of specific
      monoclonal antibodies.
AB  - Cellular recognition of immuno-stimulatory microbial products alarming the host
      immune system upon infection, as well as endogenous molecular patterns
      representing perturbation of regular homeostasis such as through necrosis of host
      cells is mediated by innate pattern recognition receptors to which toll-like
      receptors (TLRs) belong. A variety of agonists has been attributed to TLR2. We
      raised monoclonal antibodies (mAbs) toward the murine TLR2 extracellular domain
      (mT2ECD) in order to analyze murine TLR2 expression. Murine macrophages were
      stained TLR2-specifically with distinct mAbs as shown by flow cytometry, immuno
      precipitation, and immuno-cytochemical analysis. TLR2-specific murine macrophage
      activation was inhibited through pre-incubation with a mAb mT2.4 while another
      mTLR2-specific mAb mT2.7 did not affect cell activation through TLR2. Plasmon
      resonance based analysis showed inhibition of lipopeptide binding to mT2ECD if
      complex formation with mT2.4 preceded binding analysis. Systemic induction of IL
      6, IL-12p40, and GROalpha/KC release to the serum upon lipopeptide challenge of
      mice was inhibited by systemic administration of mT2.4. Furthermore, 120 mg/kg of
      mT2.4 protected mice from lethal shock-like syndrome in an experimental low-dose
      model of septic shock. This result validates blockage of cell surface TLR2 for
      inhibition of immune cell over-activation upon microbial challenge.

PMID- 15860220
TI  - Low binding capacity of murine tetramers mutated at residue 227 does not preclude
      the ability to efficiently activate CD8+ T lymphocytes.
AB  - MHC tetramers are used to directly enumerate and visualize the antigen-specific T
      lymphocyte population of interest by flow cytometry, regardless of the T
      lymphocyte's functional capacity. Assay sensitivity can be hindered by non
      specific binding activity, which is due to the inherent interactions of CD8 and
      MHC. Point mutations within the alpha3 loop of the HLA MHC class I heavy chain
      have been shown to reduce or abrogate MHC/CD8 interactions and also alleviate non
      specific binding. This report compares the effects of two well-described
      mutations on the binding capacity and functional capacity of MHC tetramers in the
      H-2 MHC murine system. Tetramers folded with MHC mutated at either residue 227 or
      245 of the class I heavy chain were compared to wild-type tetramer in binding
      studies using various antigen-specific, TCR-positive lymphocytes and cell lines.
      These experiments showed that the binding of wild-type and residue 245-mutated
      tetramer were comparable on CTL cultures, OT-1 splenocytes, and hybridomas. Both
      wild-type and 245-mutated tetramers' binding capacity was observed to be equally
      dependent on CD8 expression. Residue 227-mutated tetramer consistently bound
      antigen-specific CTL less efficiently, but in the absence of CD8 all three
      tetramers had similar binding capacity. In functional studies, 227-mutated
      tetramer had the greatest capacity to stimulate cytokine production in the
      absence of exogenous antigen addition. These experiments demonstrate that
      reduction of a tetramer's high avidity interaction with CD8 will not necessarily
      decrease the ability to stimulate the effector functions of activated T cells.

PMID- 15860221
TI  - Cytokines transduced bone marrow stromal cell lines promote immunohematopoietic
      reconstitution in mice after allogeneic bone marrow transplantation.
AB  - Impaired immune reconstitution following allogeneic T-cell depleted bone marrow
      transplantation (allo-TCD-BMT) is a major obstacle to its clinical application.
      Stromal cell line QXMSC1, established from bone marrow cells of BALB/c(H-2d), was
      transfected with murine IL-3 and/ or IL-2 gene, and injected into lethally
      irradiated C57BL/6(H2b) mice. We evaluated its effects on immunologic and
      hematopoietic reconstitution after allo-TCD-BMT. The results showed that QXMSC1
      IL-3 + IL-2 could significantly increase the numbers of hematopoietic primitive
      progenitors (CFU-S), committed progenitors (CFU-GM, and BFU-E), and lymphocytes
      (CD8+ cells, CD4+ cells, and B cells). Similarly, immune functions of recipient
      mice were significantly enhanced in the QXMSC1-IL-3 + IL-2 group. In addition,
      QXMSC1-IL-3 or QXMSC1-IL-2 also exerted apparent effects on accelerating immune
      reconstitution, but these effects were far less than that of QXMSC1-IL-3 + IL-2.
      Our results demonstrated that stromal cell-mediated IL-3 and IL-2 gene therapy
      may be a potent approach in promoting immunologic and hematopoietic
      reconstitution after allo-TCD-BMT.

PMID- 15860222
TI  - IgM production of lymphocytes from C57BL/6N mice was stimulated by estrogen
      treated splenic adherent cells.
AB  - Estrogens have diverse effects on cell growth, differentiation and homeostatic
      functions, and have been shown to play an important role in regulating immune
      system. In this study, we examined the effect of 17beta-estradiol (E2) on
      antibody production by splenocytes isolated from C57BL/6N mice. Our results
      suggest that the activation of immunoglobulin (Ig) M production by E2 requires
      direct cell-cell interaction between adherent and non-adherent cells in mouse
      splenocyte population, and the primary target of E2 is adherent cell population.
      In addition, we indicated that ER antagonist ICI 182780 suppressed this enhancing
      effect of E2. Both ERalpha agonist and ERalpha agonist enhanced IgM production of
      mouse splenocytes. ERs are expressed on plasma membrane as well as in nucleus.
      However, a plasma membrane-associated ER specific ligand has no stimulation
      effect on IgM production. In conclusion, our results indicate that adherent cells
      stimulated by E2 up-regulate IgM production of lymphocytes through the direct
      cell-cell interactions, and the enhancing effect of E2 is arouse through ERalpha
      and ERbeta on these cells.

PMID- 15860223
TI  - B-1a cell origin of the murine B lymphoma line BCL1 characterized by surface
      markers and bacterial reactivity of its surface IgM.
AB  - B cells are divided into two categories: conventional or B-2B cells and B-1B
      cells, the latter of which are distinguished by their different ontogeny. B cell
      lymphoma 1 (BCL1), the first-reported case of a spontaneously developed mouse B
      lymphoma, expresses CD5, surface IgM, Mac-1, CD43 and low level of B220, and is
      likely to have B-1a cell origin. However, antigens recognized by IgM produced by
      the BCL1 cells (BCL1-IgM) have not been identified. Here, we demonstrate that
      BCL1-IgM reacts with Escherichia coli (E. coli). Our initial finding that several
      recombinant proteins expressed in E. coli bound to BCL1-B20 prompted us to
      examine the possibility that BCL1 cells may bind E. coli. Indeed, BCL1 cells
      bound fluorescein-labeled E. coli. To elucidate the structure on the BCL1 cells
      responsible for E. coli-binding, we produced a monoclonal antibody capable of
      inhibiting BCL1 binding to E. coli. The antibody recognizes an idiotypic epitope
      on the BCL1-IgM. Moreover, polyclonal antibody against IgM and secreted BCL1-IgM
      purified from the supernatants inhibited BCL1 binding to E. coli. Finally,
      transfection of non-lymphoid cells with cDNA of heavy and light chains of BCL1
      IgM conferred the cells ability to bind E. coli. These results clearly indicate
      that BCL1-IgM bind E. coli and suggest that BCL1 lymphoma is a typical B-1 cell
      derived lymphoma, characterized not only by the surface phenotype, but also by
      the reactivity of its IgM with commensal bacteria.

PMID- 15860224
TI  - Analysis of the immune response induced by a single xenoantigen in vivo.
AB  - Transgenic mice expressing human major histocompatibility complex (MHC) class II
      molecules would provide a valuable model system for studying murine anti-human
      MHC immune response. We have previously shown that skin from HLA-DR1 transgenic
      mice was rejected by control littermates and spleen cells from rejecting mice
      were able to proliferate to donor cells. The aim of this paper is to analyze the
      mechanism of recognition of this xenoantigen and the possible involvement of
      antibody response in anti-HLA-DR1 immune response. Control littermates were
      immunized with spleen cells from HLA-DR1 transgenic (TG) mice; at indicated
      times, xenoantigen-specific proliferation and IFNgamma production was assessed
      using APC obtained from HLA-DR1 TG mice. Mixed direct-indirect pathway of
      xenoantigen recognition was suggested by the following findings: i)T cell
      response to HLA-DR1 was inhibited adding in culture monoclonal antibodies
      directed either to donor (HLA-DR) or to recipient MHC (I-A); ii) APC from control
      mice pulsed with purified DR1 molecules were able to induce proliferation by
      FVB/N mice immunized with transgenic spleen cells. HLA-DR1 recognition permits DR
      peptide-specific T cell response by lymphocytes of control littermates immunized
      with the xenoantigen. In addition, we detected xenoreactive IgM and IgG2
      antibodies. Our data suggest that HLA-DR1 xenoantigen may be recognized through
      direct or indirect pathway and provide additional information on mouse anti-human
      HLA immune response.

PMID- 15860225
TI  - Th0 to Th1 switch of CD4 T cell clones specific from the 16-kDa antigen of
      Mycobacterium tuberculosis after successful therapy: lack of involvement of
      epitope repertoire and HLA-DR.
AB  - In this study, we have examined the influence of HLA-DR molecules and the
      structure of the epitope repertoire of the 16-kDa protein of Mycobacterium
      tuberculosis on the acquisition of the cytokine secretion pattern of CD4 T cell
      clones, obtained from tuberculous patients before and after anti-mycobacterial
      therapy. Our data indicate that TB patients have a predominant Th0 response
      against the 16-kDa protein and its epitopes and that healing, induced by anti
      mycobacterial therapy, is associated with a shift toward a predominant Th1
      phenotype. Moreover, both HLA-DR molecules restricting the clone specificity and
      the nature of the recognized epitope do not play any role in the generation of
      Th0 and Th1 clones. These findings indicate that additional factors, such as the
      cytokine environment and/or costimulatory molecules, determine the Th phenotype
      of CD4 T cells during tuberculosis.

PMID- 15860226
TI  - Normal immunoglobulin gene somatic hypermutation in Pol kappa-Pol iota double
      deficient mice.
AB  - Somatic hypermutation (SHM) occurs in the variable region of immunoglobulin genes
      in germinal center B cells where it plays an important role in affinity
      maturation of the T cell-dependent immune response. Although the precise
      mechanism of SHM is still unknown, it has been suggested that error-prone DNA
      polymerases (Pol) are involved in SHM. Poliota is a member of the error-prone Y
      family of DNA polymerases which exhibit translesion synthesis activity in vitro
      and are highly mutagenic when replicating on non-damaged DNA templates. In BL2
      cell line stimulated to induce SHM, the induction is Poliota-dependent. However,
      in 129-derived strains of mice deficient in Poliota, SHM is normal. One possible
      explanation for this discrepancy is that a Poliota deficiency in mice might be
      compensated for by another error-prone DNA polymerase, such as Polkappa, which
      also belongs to the Y-family of DNA polymerases. Although SHM in Polkappa
      deficient mice is normal, their deficiency might be compensated for by Poliota.
      In this study, we generated Polkappa-Poliota double-deficient mice and examined
      them for SHM. We found that the double-deficient mice had the normal SHM
      frequency and profile, rendering them indistinguishable from Polkappa-deficient
      mice and thus conclude that Poliota and Polkappa are dispensable for SHM in mice.

PMID- 15860227
TI  - Differential gene expression profile between cord blood progenitor-derived and
      adult progenitor-derived human mast cells.
AB  - In order to better understand the mechanisms governing the display of mast cell
      characteristics in human mast cells (MCs), such as cord blood (CB)-derived
      cultured mast cells, peripheral blood (PB)-derived cultured MCs, and
      differentiated adult-lung cultured MCs, we examined the transcriptomes of these
      three types MCs using oligonucleotide microarray (GeneChip) and hierarchical
      clustering analysis. The expression profile of CB-derived MCs substantially
      differed from those of PB- and lung-derived MCs. In CB-derived MCs, we identified
      132 up-regulated transcripts, such as MARCKS, KRT1, TIMP2, SERPINA1, and TLR2,
      and 428 down-regulated transcripts, such as LTBP3, CDC42BPA, DDO, DICER1, and
      FCER1A. Moreover, using RT-PCR and FACS analysis, we confirmed the expression of
      TLR2, which plays an important role in innate immunity, in CB-derived MCs but not
      in PB-derived MCs. In addition, it was observed that CB-derived MCs uniquely
      release histamine and CCL1, which are produced by human MCs but not by human
      monocytes, in response to peptidoglycan (PGN), although it had been controversy
      issue whether CB-derived MCs could, in fact, induce degranulation in response to
      PGN. These results indicated that in innate immunity MCs derived from neonatal
      hemopoietic cells might have unique functions compared to their adult
      counterparts because of different gene profiles.

PMID- 15860228
TI  - Gene expression profiling of dexamethasone-treated RBL-2H3 cells: induction of
      anti-inflammatory molecules.
AB  - Glucocorticoids are well known for their anti-inflammatory effect through the
      regulation of gene expression in many types of immune cells, including mast
      cells. However, the genes that are involved in suppression of mast cell-mediated
      inflammation by glucocorticoids have not been fully identified. Therefore, we
      examined the dexamethasone (Dex)-responsive genes in RBL-2H3 mast cells using a
      high-density oligonucleotide microarray technique. Gene expression profiling
      revealed that the antigen-induced up-regulation of pro-inflammatory factors,
      including monocyte chemoattractant protein-1, was markedly inhibited by 100 nM
      Dex. On the other hand, Dex treatment itself caused the substantial up-regulation
      of many genes, including phenylethanolamine-N-methyl transferase (PNMT) and
      cytokine-inducible SH2-containing protein (CISH), in the mast cells. The
      expression of these two genes significantly increased 6 h after Dex exposure and
      lasted for more than 24 h. Considering that PNMT is the rate-determining enzyme
      in epinephrine synthesis and that CISH is a suppressor of cytokine signaling,
      these Dex-responsive genes may be potential anti-inflammatory factors. Thus, gene
      expression profiling suggested that Dex might exert its anti-inflammatory effect
      through two pathways in mast cells: the suppression and induction of potentially
      pro- and anti-inflammatory factors, respectively.

PMID- 15860229
TI  - Gene-inducing program of human dendritic cells in response to BCG cell-wall
      skeleton (CWS), which reflects adjuvancy required for tumor immunotherapy.
AB  - Adjuvants induce the expression of a number of genes in dendritic cells (DCs),
      which facilitate effective antigen-presentation and cytokine/chemokine
      liberation. It has been accepted that the toll-like receptor (TLR) family governs
      the adjuvant activity in DCs. An adjuvant with a long history is mycobacteria in
      an oil-in-water emulsion, namely Freund's complete adjuvant. Since the active
      center for the adjuvancy in mycobacteria is the cell-wall skeleton (CWS), we used
      the bacillus Calmette-Guerin cell-wall skeleton (BCG-CWS) to test DC maturation
      by GeneChip analysis. We identified the genes supporting an efficient DC response
      and output. Approximately 2000 genes were up-regulated by BCG-CWS stimulation.
      BCG-CWS-, peptidoglycan (PGN)- and lipopolysaccharide (LPS)-stimulation generally
      up-regulated some gene clusters including genes for inflammatory cytokines (TNF,
      IL1alpha, IL1beta, IL6, IL12 p40, IL23 p19, etc.), chemokines (CCL20, IL8, etc.),
      cell adhesion molecules (ICAM-1, etc.), apoptosis-related proteins (GADD45B,
      BCL2A1, etc.), metabolic enzymes (PTGS2, SOD2, etc.) and miscellaneous proteins
      (EHD1, TNFAIP6, etc.). LPS-stimulation, but not BCG-CWS- or PGN-stimulation, up
      regulated the interferon-inducible antiviral proteins, including IFIT1, IFIT2,
      IFIT4, CXCL10, ISG15, OASL, IFITM1 and MX1. We also found that the BCG-CWS- or
      PGN-stimulation up-regulated CXCL5, MMP1, etc. We discussed their properties in
      association with TLRs and recently discovered TLR adapters.

PMID- 15860230
TI  - Regulation of IL-18 expression by CRH in mouse microglial cells.
AB  - Corticotropin releasing hormone (CRH) is a major regulator of the stress
      response. This study examined whether CRH regulates interleukin-18 expression on
      microglia, BV2. Our data show that CRH enhanced IL-18 expression and
      significantly induced the secretion of functional IL-18 protein. Furthermore, CRH
      induced IL-18 production could be blocked by N-acetyl-L-cystein (NAC), which
      suggests that reactive oxygen intermediates (ROI) may be involved in regulating
      IL-18. Indeed, it was also found that CRH increased the generation of ROI. Taken
      together, these results indicate that CRH is an important mediator that regulates
      IL-18 expression in the brain during stress.

PMID- 15860231
TI  - Annexins I and IV inhibit Staphylococcus aureus attachment to human macrophages.
AB  - Annexins are a family of proteins that bind to phospholipids and carbohydrates in
      a calcium-dependent manner. They are present in a variety of body fluids.
      Previous studies have shown that annexins have anti-inflammatory activities for
      lipid A of Gram-negative bacteria. The present study investigated the effect of
      annexins on interaction between Gram-positive bacteria and immune cells such as
      macrophages. Annexins I and IV bound to lipoteichoic acids which are surface
      molecules on Gram-positive bacteria. Binding of annexins I and IV to whole
      Staphylococcus aureus (S. aureus) were observed and these bindings were inhibited
      by lipoteichoic acid from S. aureus. Moreover, annexins I and IV suppressed the
      attachment of S. aureus to phorbol 12-myristate 13-acetate-treated THP-1 cells
      (human macrophages). These results suggest that annexins I and IV have ligand
      specificities toward foreign substances, and that the annexins might have some
      anti-inflammatory property for Gram-positive bacteria.

PMID- 15860232
TI  - Anti-IgM induces up-regulation and tyrosine-phosphorylation of heterogeneous
      nuclear ribonucleoprotein K proteins (hnRNP K) in a Ramos B cell line.
AB  - Heterogeneous nuclear ribonucleoprotein K protein (hnRNP K) has diverse molecular
      partners implicated in signal transduction pathways, and is tyrosine
      phosphorylated in response to growth factors and oxidative stress. Among the
      structurally distinct domains of hnRNP K, an SH3-binding domain (SH3BD) has been
      known to promote the association of SH3-containing tyrosine kinases and
      protooncoprotein Vav, which are involved in B cell receptor (BCR) signalling. In
      this study, we analyzed proteins of Ramos B cell line that are altered upon BCR
      activation with anti-IgM antibody, revealing that a certain hnRNP K isoform is up
      regulated in response to anti-IgM treatment. We also showed that hnRNP K is
      tyrosine-phosphorylated after BCR ligation. HnRNP K lacking the SH3BD is shown
      not to interact with phosphorylated Vav, and Ramos cells stably expressing this
      mutant protein are less susceptible to anti-IgM-induced apoptosis, indicating
      that hnRNP K is coupled to BCR-mediated signalling and its SH3BD is required for
      proper signal propagation. Our results provide the first evidence that hnRNP K is
      involved in BCR signalling pathway.

PMID- 15860233
TI  - Rational design of potent mimic peptide derived from monoclonal antibody:
      antibody mimic design.
AB  - The variable regions of antibody molecules bind antigens with high affinity and
      specificity. The binding sites are imparted largely to the hypervariable portions
      (i.e. CDRs) of the variable region. Peptides derived from antibody CDRs can bind
      antigen with similar specificity acted as mimic of antibody and become drug
      designing core, although with markedly lower affinity. In this study, the 3D
      complex structure of tumor necrosis factor-alpha (TNFalpha) and its neutralizing
      monoclonal antibody Z12 was modeled using molecular docking method and optimized
      with molecular mechanism and dynamics method. The binding domains between
      TNFalpha and Z12 were determined theoretically and functional antigen epitopes
      were predicted. According to the 3D complex structure of TNFalpha and Z12, a
      novel antagonist peptide, named PT1, was designed theoretically. The experimental
      result showed that PT1 possessed significantly binding inhibition of TNFalpha to
      Z12 and protected L929 cells from the cytotoxic effect of TNFalpha. The designed
      mimic peptide was more amenable to synthetic chemistry and thus might be useful
      starting points for the design of smaller organic mimics.

PMID- 15860234
TI  - 1st Conference of Basic and Clinical Immunogenomics, 3-7 October, 2004, Budapest,
      Hungary (www.diamond-congress.hu/bci2004/).

PMID- 15860235
TI  - Effects of repaglinide on oxidative stress in tissues of diabetic rabbits.
AB  - In this study, the antioxidative properties of repaglinide were examined in
      tissues of alloxan-induced diabetic rabbits. Glutathione (GSH), glutathione
      peroxidase (GSH-Px), glutathione reductase (GSSG-R) and protein carbonyl groups
      (PCG) were measured after 4 and 8 weeks treatment with repaglinide (0.3 mg/kg
      daily). In liver, diabetic versus control values (mean +/- S.E.M., p<0.05) for
      GSH-Px were 181.0 +/- 5.4 mU/mg protein versus 203.1 +/- 1.9 mU/mg protein and
      187.4 +/- 6.6 mU/mg protein versus 240.9 +/- 18.8 mU/mg protein. The respective
      values for GSH were 33.7 +/- 0.4 nmol/mg protein versus 49.0 +/- 1.6 nmol/mg
      protein and 37.7 +/- 1.0 nmol/mg protein versus 41.2 +/- 0.7 nmol/mg protein. In
      diabetic kidney, GSSG-R activity (20.6 +/- 1.6 mU/mg protein versus 32.4 +/- 1.5
      mU/mg protein and 23.6 +/- 0.6 mU/mg protein versus 36.3 +/- 0.3 mU/mg protein)
      and GSH level (16.6 +/- 0.5 nmol/mg protein versus 23.2 +/- 0.9 nmol/mg protein
      and 17.9 +/- 0.5 nmol/mg protein versus 23.2 +/- 0.6 nmol/mg protein) were
      reduced compared to control. PCG level was elevated in diabetic liver (0.58 +/-
      0.02 nmol/mg protein versus 0.16 +/- 0.03 nmol/mg protein at 4 weeks and 0.64 +/-
      0.04 nmol/mg protein versus 0.16 +/- 0.03 nmol/mg protein at 8 weeks) and in
      diabetic kidney (0.32 +/- 0.03 nmol/mg protein versus 0.11 +/- 0.02 nmol/mg
      protein and 0.35 +/- 0.03 nmol/mg protein versus 0.16 +/- 0.03 nmol/mg protein).
      Repaglinide did not affect the glucose level but reduced to some extent the
      oxidative stress enhanced by chronic hyperglycemia. In diabetic kidney, it
      restored to control values GSSG-R activity (45.4 +/- 2.0 mU/mg protein at 4 weeks
      and 41.1 +/- 0.07 mU/mg protein at 8 weeks), GSH level (27.0 +/- 0.8 and 26.8 +/-
      0.9 nmol/mg protein), and partly PCG level (0.17 +/- 0.02 nmol/mg protein at 8
      weeks). The treatment partly affected GSH-Px activity (262.7 +/- 17.6 mU/mg
      protein) and GSH level (40.4 +/- 1.4 nmol/mg protein) in diabetic liver. This
      study shows that repaglinide produces measurable antioxidative effects at
      therapeutic dose.

PMID- 15860236
TI  - Optimal use of quick-acting insulin analogue in combination with basal insulin
      and its long-term effect in Japanese children and adolescents with type 1
      diabetes.
AB  - The aim of the study was to examine the optimal use of quick-acting insulin
      analogue (Q) switching from regular insulin (R) in combination with basal insulin
      and its long-term effects in 40 Japanese children and adolescents with type 1
      diabetes. Insulin regimens after administration of Q were increased to twice
      daily injections of basal insulin and modified use of Q or R as bolus insulin
      depending on the blood glucose profile and lifestyles. The mean dose of total
      insulin remained unchanged during treatment with using Q, but that of basal
      insulin increased 12 months after the use of Q (baseline: 25.8 +/- 12.2, after 12
      months: 27.1 +/- 12.6 U/day). After switching to Q, the mean HbA1c value
      decreased in all patients (baseline: 7.6 +/- 1.0, after 12 months: 7.3 +/- 0.8%),
      which reflected improvement of HbA1c in patients with HbA1c > or = 8% at
      baseline. These results indicated that insulin regimens after switching from R to
      Q varied with increases of the number and the dosage of basal insulin. Use of Q
      seems to be useful to improve hyperglycemia in patients with a poor glucose
      profile under conventional insulin treatment with using R. The choice of insulin
      regimens with using Q in consideration of the blood glucose profile as well as
      lifestyles may lead to better glycemic control.

PMID- 15860237
TI  - Effect of pioglitazone on arteriosclerosis in comparison with that of
      glibenclamide.
AB  - BACKGROUND: Pioglitazone is an insulin-sensitizing agent that has been reported
      to have anti-arteriosclerotic effects. OBJECTIVE: To investigate the anti
      arteriosclerotic effects of pioglitazone in patients with diabetes mellitus using
      pulse wave velocity (PWV) as an index of efficacy. METHODS: Twenty-seven patients
      with type 2 diabetes mellitus were randomly assigned to two groups, and
      pioglitazone (n=13) or glibenclamide (n=14) was administered for 6 months. The
      TG, TC, LDL-C, and HDL-C, FPG, HbA1c, IRI levels, HOMA-IR, and ba-PWV data were
      examined before and after administration of each agent. RESULTS: FPG and HbA1c
      were significantly improved in both the groups after treatment, but IRI, HOMA-IR
      and were improved only in the PIO group. The percent change of ba-PWV from the
      baseline after treatment in the PIO group improved significantly than that in the
      GC group (-6.3 +/- 5.6% versus 0.8 +/- 5.7%). CONCLUSIONS: The findings in this
      study suggested that pioglitazone has anti-arteriosclerotic effects. We concluded
      that drugs for the treatment of diabetes mellitus should be selected taking into
      consideration such endpoints as blood sugar control, and also the risk of
      complications such as cardiovascular events in the future.

PMID- 15860238
TI  - CTLA-4 +49 A/G polymorphism is associated with predisposition to type 1 diabetes
      in Iranians.
AB  - CTLA-4 is a homeostatic regulator of T cell activation and is believed to play a
      critical role in peripheral tolerance. The contribution of CTLA-4 gene variants
      to type 1 diabetes has been analyzed in several ethnic groups. In this study, the
      association of CTLA-4 +49 A/G polymorphism with type 1 diabetes was investigated
      in Iranian patients. One hundred and nine patients and 331 healthy subjects
      formed the studied populations. CTLA-4 A/G polymorphism at position 49 in exon 1
      was identified using PCR-SSCP and PCR-RFLP methods. Patient numbers with A/G, A/A
      and G/G genotypes were 78 (71.5%), 21 (19.3%) and 10 (9.2%) while in healthy
      controls, these were 149 (45%), 146 (44.2%) and 36 (10.8%), respectively. A
      significant decrease in the frequency of the A/A genotype was observed in the
      diabetes group (p = 0.000004). In diabetic subjects, the allele frequency of G
      was also higher than in controls (45% versus 33.4%, p = 0.00269). The differences
      in the genotypes and the alleles were greater in patients with younger age of
      diabetes onset (age < or = 15 years) compared with controls (p = 0.000001 and p =
      0.000579, respectively). The distribution of the CTLA-4 polymorphism between
      patients did not show any significant difference according to diabetic
      ketoacidosis at onset. In conclusion, the result of this study in combination
      with the previous reports of other ethnic populations showed that CTLA-4 +49 A/G
      polymorphism confers genetic susceptibility to type 1 diabetes, particularly in
      younger individuals.

PMID- 15860239
TI  - Osteoclastic function is accelerated in male patients with type 2 diabetes
      mellitus: the preventive role of osteoclastogenesis inhibitory
      factor/osteoprotegerin (OCIF/OPG) on the decrease of bone mineral density.
AB  - To clarify the pathogenesis of altered bone metabolism in diabetic state and its
      underlying mechanisms, the bone mineral content and fasting levels of serum
      intact parathyroid hormone (i-PTH), intact osteocalcin (i-OC), tartrate-resistant
      acid phosphatase (TRAP) and osteoclastgenesis inhibitory factor/osteoprotegerin
      (OCIF/OPG) were measured in male type 2 diabetic patients and their age-matched
      controls. In addition, urine levels of osteoclastic markers, C-telopeptide of
      type I collagen (CTx), deoxypyridinoline (DPD), and N-telopeptide of type I
      collagen (NTx) were simultaneously determined. Serum levels of i-PTH and i-OC in
      diabetic patients were significantly lower than those in the controls.
      Conversely, serum concentrations of TRAP were significantly elevated in diabetic
      patients. However, no clear correlation was observed between serum i-OC and TRAP.
      It was also observed that urinary excretion of CTx, DPD, and NTx was
      significantly increased in the diabetics as compared with the controls.
      Unexpectedly, serum levels of OCIF/OPG tended to be higher in the diabetic group,
      and these values exhibited a significantly positive correlation with those of
      serum TRAP. There was found a significantly negative correlation between serum
      TRAP and bone mineral density (BMD) and also between serum OCIF/OPG and bone
      mineral density. It seems probable that OCIF/OPG has a suppressive role on the
      increased bone resorption to prevent further loss of the skeletal bone mass in
      type 2 diabetic patients.

PMID- 15860240
TI  - Introduction of diabetes passports involving both patients and professionals to
      improve hospital outpatient diabetes care.
AB  - AIM: To investigate whether a comprehensive strategy involving both patients and
      professionals, with the introduction of a diabetes passport as a key component,
      improves diabetes care. METHODS: The first 150 consecutive patients who visited
      their internist for a diabetes check up at the internal medicine outpatient
      departments at each of nine Dutch general hospitals were included in this 1 year
      clustered, randomised, controlled trial. Health care professionals attended an
      educational meeting about the use and dissemination of the diabetes passport
      which is a patient held record. They also received aggregated feedback on
      baseline data and personal feedback. Educational meetings were also organised for
      patients. Patient files were used in conjunction with questionnaires to determine
      adherence rates. Data were analysed using multilevel regression analysis.
      RESULTS: Small but significant changes were found in mean HbA1c levels. In the
      intervention group, positive health changes for patients were found (-0.3%) when
      compared to those in the control group (+0.2%). Diastolic blood pressure improved
      slightly, but no changes were found in systolic blood pressure or cholesterol.
      Improvements were found with regard to levels of examination of patients' feet
      and in patient education. CONCLUSIONS: Efforts to improve professional practice
      involving both professionals and patients led to small improvements in HbA1c and
      diastolic blood pressure levels. Further study is needed to establish whether a
      better structured health care delivery, operating in a more supportive
      environment can enhance these effects.

PMID- 15860241
TI  - A diabetes intervention program of physical activity carried out at primary care
      settings in Mexico.
AB  - OBJECTIVE: The aim of this study was to document physical activity (PA) of
      migrant Mexican women with type 2 diabetes who have participated in diabetes
      intervention programs at a primary care level. METHODS: One hundred out of 133
      women of seven diabetes education groups from different Mexican institutions
      located in the city of Tijuana were invited to participate in the study. A PA
      history questionnaire was completed weekly. Metabolic Equivalents (METs) were
      used to calculate physical activity level (PAL). RESULTS: Forty percent were
      classified as overweight and 31% as obese. Six percent of the women performed
      more than 150 min of moderate/vigorous weekly PA, while more than 80 min of
      weekly PA was reported by 73% of the population. There was no difference in
      frequency and intensity of PA between the participants from both institutions.
      The main indoor activities were cooking, dish washing, clothes washing and
      cleaning, and the main outdoor activities were walking, semi-active exercise and
      running. CONCLUSIONS: The majority of these migrant women who participated in the
      diabetes intervention program seem to engage in the minimum recommended levels of
      PA. In a country like Mexico, where its public health care system is facing huge
      economic constraints, PA counseling done in a primary health care practice may be
      a cost-effective approach.

PMID- 15860242
TI  - Features and outcome of pregnancies complicated by impaired glucose tolerance and
      gestational diabetes diagnosed using different criteria in a Spanish population.
AB  - The main objective of this study was to determine the prevalence and risk of
      complications of a population of Spanish pregnant women with GDM diagnosed
      following the O'Sullivan-Mahan "standard" criteria, compared with pregnant women
      with GDM diagnosed using the "new" Carpenter-Coustan criteria. In Spain, limited
      data are published concerning as the prevalence of GDM and its morbidity. In this
      sense, the "new" criteria for GDM diagnosis has not been adopted in Spain due to
      the absence of adequate studies. We retrospectively reviewed all pregnancies
      handled at our center from 1999 to 2001 (n=6248). Using the standard and the new
      criteria, the prevalence of GDM was 6.46 and 6.75%, respectively. GDM patients
      diagnosed using the new criteria showed the same pregnancy evolution that
      patients diagnosed with the classic criteria. Those patients complicated only
      with impaired glucose intolerance (IGT) (0.94%) showed a worst outcome. Based on
      the pregnancy evolution observed, it is not recommended that the new GDM
      diagnostic criteria be adopted in Spain. More accurate follow-up of patients with
      IGT is needed.

PMID- 15860243
TI  - Glucose intolerance and all-cause mortality in Japanese migrants.
AB  - OBJECTIVE: To assess all-cause mortality in a Japanese-Brazilian community
      according to the categories of glucose tolerance. STUDY DESIGN AND SETTING: The
      cohort consisted of participants examined in two phases of a follow-up study
      started in 1993 (n=647). They were interviewed and submitted to an oral glucose
      tolerance test. Student's t-test was used to compare baseline parameters between
      alive and dead subjects. Cox proportional hazards model was used to estimate
      crude and adjusted hazard ratios (HR). RESULTS: Seventy-one deaths occurred
      during the study period and a higher proportion of men (62%) was detected. Crude
      all-cause mortality rate was 16.2/1000 person-year. Vascular disease and cancer
      were the most frequent causes of deaths (77.3%). A higher mortality rate was
      observed in subjects with diabetes when compared with the normal glucose tolerant
      ones (HR: 2.0; 95% CI: 1.1-3.6), independently of age, systolic blood pressure,
      smoking and history of myocardial infarction. CONCLUSION: Also among Japanese
      living in the Western world, a deleterious role of fasting and 2-h plasma glucose
      was found on mortality especially among younger subjects.

PMID- 15860244
TI  - Variants of calpain-10 gene and its association with type 2 diabetes mellitus in
      a Chinese population.
AB  - Variants of calpain-10 gene (CAPN 10) have recently been reported to be
      associated with type 2 diabetes (T2DM). Haplotype combination 112/121 defined by
      three single nucleotide polymorphisms (SNPs) (UCSNP-43, -19 and -63) of CAPN 10
      conferred the highest risk for T2DM in Mexican-Americans. In this study, we aim
      to examine whether these genetic variants contribute to the susceptibility for
      T2DM in a Chinese population. The frequencies of these three SNPs were determined
      in 168 patients with T2DM and 104 controls. Distribution of alleles, genotypes
      and haplotypes at three loci were not significantly different between the two
      groups. No difference was observed in the 112/121 haplotype combination
      distribution. However, haplotype combination 112/221 was more prevalent in the
      control group than in T2DM group (16.35% versus 7.14%, p = 0.025). Control
      subjects with haplotype combination 112/121 had higher serum cholesterol level
      than others without haplotype combination 112/121 (5.7 +/- 1.4 versus 5.2 +/-
      0.7, p = 0.011). Our results suggest that haplotype combination 112/221
      associated with reduced risk for T2DM and haplotype combination 112/121 might be
      a risk factor for increased serum cholesterol in Chinese population.

PMID- 15860245
TI  - Arterial stiffness is associated with diabetic retinopathy in type 2 diabetes.
AB  - The purpose of this study was to investigate the association between arterial
      stiffness and diabetic retinopathy. The subjects comprised 1004 patients with
      type 2 diabetes. Pulse-wave velocity (PWV) was used as a marker of arterial
      stiffness. Clinical characteristics, including PWV and diabetic retinopathy (DR),
      were investigated in a cross-sectional study. PWV, duration of diabetes, systolic
      blood pressure and hemoglobin A1c level were all significantly higher in patients
      with diabetic retinopathy than in individuals without this disorder. The
      association between brachial-ankle PWV and diabetic retinopathy remained
      significant after statistical adjustment, with increasing odds ratios (ORs) from
      the second quartile (OR, 2.09; 95% confidence interval (CI), 1.21-3.61), to the
      third (OR, 2.80; 95% CI, 1.61-4.86) and fourth (OR, 4.64; 95% CI, 2.54-8.52)
      quartiles. Diabetic retinopathy was, therefore, associated with arterial
      stiffness in patients with type 2 diabetes. Our findings also suggested that PWV
      might be a marker of vascular injury caused by chronic hyperglycemia.

PMID- 15860246
TI  - Effect on glycemic control of the addition of 2.5 mg glipizide GITS to metformin
      in patients with T2DM.
AB  - AIMS: This study evaluated the effects on glycemic control of the addition of 2.5
      mg glipizide GITS to metformin in patients with mild-to-moderate, but
      suboptimally controlled type 2 diabetes. METHODS: In this multicenter, double
      blind, placebo-controlled study, 122 patients with type 2 diabetes inadequately
      controlled (A1c 7-8.5%) on metformin (> or =1000 mg/day for > or =3 months) were
      randomized to 16 weeks treatment with 2.5 mg/day glipizide GITS (n=61) or placebo
      (n=61), in addition to their current metformin dose. The primary efficacy
      variable was the change in A1c from baseline to endpoint. Changes in fasting
      plasma glucose (FPG), insulin concentrations, lipid profile and safety variables
      were also measured. RESULTS: The addition of glipizide GITS to metformin gave
      significantly greater improvements in mean A1c and FPG from baseline to endpoint
      than placebo addition (p<0.0002). Significantly more patients in the glipizide
      GITS group than in the placebo group achieved the target A1c level of A1c<7.0%
      (p<0.0001) and an A1c<6.5% (p<0.0033). Fasting insulin concentrations were
      similar in both groups and unchanged by treatment. Addition of glipizide GITS to
      metformin did not produce any significant or clinically relevant weight gain or
      changes in BMI. Both treatment regimens were well tolerated. CONCLUSIONS: This
      study showed that the addition of 2.5 mg glipizide GITS to metformin
      significantly improved glucose control in patients with type 2 diabetes
      inadequately controlled by metformin monotherapy.

PMID- 15860247
TI  - Camel milk as an adjunct to insulin therapy improves long-term glycemic control
      and reduction in doses of insulin in patients with type-1 diabetes A 1 year
      randomized controlled trial.

PMID- 15860248
TI  - Action and research are needed for evaluation of optimal definitions of
      anthropometric parameters and metabolic syndrome for Asians.

PMID- 15860250
TI  - Nuclear hormone receptor co-repressors.
AB  - Gene silencing is an essential transcriptional regulatory process. Co-repressors
      mediate gene repression through their recruitment by DNA bound transcriptional
      silencer proteins. Co-repressors repress gene expression through several
      mechanisms, mostly investigated on the level of chromatin. Lack or aberrant gene
      silencing is associated with many defects both on cellular and organismic level.
      Several human diseases are based on dysregulated co-repressor binding to
      transcriptional silencers indicating that co-repressor recruitment and the
      strength of gene silencing must be under strict control. In line with that gene
      silencing is important for animal development, cellular proliferation and
      transformation. Co-repressors play also a major role in the treatment of hormone
      dependent growing cancers, such as for breast and prostate cancer therapy. The
      molecular basis of anti-hormone therapy lies in the recruitment of co-repressors
      to the estrogen or androgen receptors, respectively, which leads to their
      inactivation and to inhibition of cancer growth. The molecular mechanisms of
      selected topics are summarized here.

PMID- 15860251
TI  - Multiple expression control mechanisms of peroxisome proliferator-activated
      receptors and their target genes.
AB  - The peroxisome proliferator-activated receptors (PPAR) alpha, beta/delta and
      gamma belong to the nuclear hormone receptor superfamily. As ligand-activated
      receptors, they form a functional transcriptional unit upon heterodimerization
      with retinoid X receptors (RXRs). PPARs are activated by fatty acids and their
      derivatives, whereas RXR is activated by 9-cis retinoic acid. This heterodimer
      binds to peroxisome proliferator response elements (PPRE) residing in target
      genes and stimulates their expression. Recent reports now indicate that PPARs and
      RXRs can function independently, in the absence of a hetero-partner, to modulate
      gene expression. Of importance, these non-canonical mechanisms underscore the
      impact of both cofactors and DNA on gene expression. Furthermore, these different
      mechanisms reveal the increasing repertoire of PPAR 'target' genes that now
      encompasses non-PPREs containing genes. It is also becoming apparent that
      understanding the regulation of PPAR expression and activity, can itself have a
      significant influence on how the expression of subgroups of target genes is
      studied and integrated in current knowledge.

PMID- 15860252
TI  - Evaluation of steroid receptor function by gene targeting in mice.
AB  - Corticosteroid hormones regulate a variety of developmental, physiological and
      pathological processes via their cognate receptors, the glucocorticoid receptor
      (GR) and the mineralocorticoid receptor (MR). Using modern genetic technologies,
      including bacterial artificial chromosome-based transgenesis and conditional gene
      targeting, we have generated a panel of tissue-specific and function-selective
      mutations of the two corticosteroid hormone receptors in the mouse. These mouse
      models have allowed us to gain new insights into corticosteroid hormone signaling
      in vivo. By investigating a hepatocyte-specific GR mutation, it has been possible
      to define a novel biological action of GR, namely to function as a coactivator
      for Stat5-mediated gene transcription in the control of body growth. The
      investigation of brain-specific mutations have not only allowed us to better
      understand hypothalamo-pituitary-adrenal (HPA) axis regulation by
      glucocorticoids, but also to analyse corticosteroid action in various aspects of
      brain function like anxiety-related or addiction-related behaviour, and learning
      and memory. A function-selective mutation in the GR has allowed us to dissect
      different pathways in the gene expression regulation by this receptor, namely to
      separate DNA response element-binding dependent gene activation from response
      element-independent gene regulation via interference with other transcription
      factors. These different transcriptional activities of GR play an important role
      in glucocorticoid-mediated immunosuppression.

PMID- 15860253
TI  - New insights into the molecular endocrinology of parturition.
AB  - The signals that lead to the initiation of parturition have remained a mystery.
      We postulate that in humans and other mammals, uterine quiescence is maintained
      by increased progesterone receptor (PR) transcriptional activity, and spontaneous
      labor is initiated or facilitated by a concerted series of biochemical events
      that negatively impact PR function. In recent studies, we have obtained
      compelling evidence to suggest that the fetus signals the initiation of labor by
      secretion into amniotic fluid of major lung surfactant protein, SP-A. SP-A
      expression is developmentally regulated in fetal lung and is secreted into
      amniotic fluid in high concentrations near term (after 17 days postcoitum [dpc]
      in the mouse). We found that injection of exogenous SP-A into mouse amniotic
      fluid at 15 dpc caused preterm labor. SP-A activated amniotic fluid macrophages
      in vitro to express nuclear factor kappaB (NF-kappaB) and interleukin-1beta (IL
      1beta). These macrophages, which are of fetal origin, migrate to the pregnant
      uterus causing an inflammatory response and increased uterine NF-kappaB activity.
      We suggest that the increase in NF-kappaB within the maternal uterus both
      directly increases expression of genes that promote uterine contractility and
      negatively impacts the capacity of the PR to maintain uterine quiescence,
      contributing to the onset of labor. Our findings, therefore, indicate that SP-A
      secreted into amniotic fluid by the maturing fetal lung serves as a hormone of
      parturition.

PMID- 15860254
TI  - RALES, EPHESUS and redox.
AB  - In RALES, low doses of the mineralocorticoid receptor (MR) antagonist
      spironolactone, added to standard of care for severe heart failure, improved
      survival by 30% and lowered hospitalization by 35%. Animal studies with the
      selective MR antagonist eplerenone have similarly shown MR blockade to prevent
      the cerebral, renal and coronary vascular inflammatory response to elevated
      aldosterone levels. There is now general acceptance that aldosterone
      concentrations inappropriate for salt status have major deleterious effects on
      the cardiovascular system. In many instances, however (e.g. Randomized Aldactone
      Evaluation Study (RALES), EPHESUS) aldosterone levels are normal and salt status
      unremarkable and yet MR blockade has unquestioned benefits. In these instances,
      there is increasing evidence that coronary and cardiac MR are activated by normal
      circulating cortisol levels, in the cellular context of generation of reactive
      oxygen species (ROS) and/or alteration in intracellular redox status. MR in VSMC
      and cardiomyocytes are normally predominantly occupied by cortisol in tonic
      inhibitory mode. Blockade of 11beta hydroxysteroid dehydrogenase type II
      (11betaHSD2) or ROS generation both serve to activate cortisol-MR complexes, thus
      mimicking the effects of mineralocorticoid/salt imbalance on blood vessels and
      the heart. In RALES and EPHESUS, it is likely that the antagonists are blocking
      normal levels of cortisol, not aldosterone, from activating MR in the context of
      tissue damage and ROS generation. If this is the case, MR antagonists may be of
      wide therapeutic potential in cardiovascular disease and not confined to those
      characterized by aldosterone/salt excess. Finally, the pathophysiologic roles of
      always-occupied MR in 'unprotected' tissues such as cardiomyocytes or neurons in
      response to altered intracellular redox status remain to be explored.

PMID- 15860255
TI  - Conformational adaptation of nuclear receptor ligand binding domains to agonists:
      potential for novel approaches to ligand design.
AB  - Ligands occupy the core of nuclear receptor (NR) ligand binding domains (LBDs)
      and modulate NR function. X-ray structures of NR LBDs reveal most NR agonists
      fill the enclosed pocket and promote packing of C-terminal helix 12 (H12),
      whereas the pockets of unliganded NR LBDs differ. Here, we review evidence that
      NR pockets rearrange to accommodate different agonists. Some thyroid hormone
      receptor (TR) ligands with 5' extensions designed to perturb H12 act as
      antagonists, but many are agonists. One mode of adaptation is seen in a
      TR/thyroxine complex; the pocket expands to accommodate a 5' iodine extension.
      Crystals of other NR LBDs reveal that the pocket can expand or contract and some
      agonists do not fill the pocket. A TRbeta structure in complex with an isoform
      selective drug (GC-24) reveals another mode of adaptation; the LBD hydrophobic
      interior opens to accommodate a bulky 3' benzyl extension. We suggest that
      placement of extensions on NR agonists will highlight unexpected areas of
      flexibility within LBDs that could accommodate extensions; thereby enhancing the
      selectivity of agonist binding to particular NRs. Finally, agonists that induce
      similar LBD structures differ in their activities and we discuss strategies to
      reveal subtle structural differences responsible for these effects.

PMID- 15860256
TI  - Rush hour at the promoter: how the ubiquitin-proteasome pathway polices the
      traffic flow of nuclear receptor-dependent transcription.
AB  - Nuclear receptor-dependent transcription requires the functional activities of
      many proteins in order to achieve proper gene expression. Progress in
      understanding transcription mechanisms has revealed the unexpected involvement of
      the ubiquitin-proteasome pathway in the transcriptional process. In some
      instances, stabilization of the transcription protein augments the functional
      role or activation state of that protein, but other evidence supports the
      hypothesis that degradation of that factor may be required in order for
      transcription to proceed. Perhaps most peculiar is the observation that several
      yeast models support the uncoupling of ubiquitylation from concomitant proteasome
      mediated degradation, with the former responsible for regulating
      posttranslational modification of histones and controlling differential
      recruitment of a transcription factor to distinct promoters. Additionally, the
      ATPases of the 19S proteasome regulatory cap have been shown to function in
      transcription elongation, independently of their role in proteolysis. This review
      summarizes and discusses progress thus far in integrating the disparate fields of
      ubiquitylation and proteasome-mediated protein degradation with gene
      transcription.

PMID- 15860257
TI  - Glucocorticoid-induced apoptosis and glucocorticoid resistance in acute
      lymphoblastic leukemia.
AB  - Glucocorticoids (GC) induce cell cycle arrest and apoptosis in lymphoid cells,
      and therefore constitute a central component in the treatment of lymphoid
      malignancies, particularly childhood acute lymphoblastic leukemia (ALL). In spite
      of its clinical significance and considerable efforts in many laboratories,
      however, the molecular basis of GC-induced apoptosis and the clinically important
      resistance phenomenon remains poorly defined. The anti-leukemic GC effects are
      critically dependent upon sufficient expression of the GC receptor (GR)
      throughout the response. In ALL cell lines, this is associated with, and may
      depend upon, GR autoinduction. In corresponding in vitro models, GC resistance
      frequently results from mutations in the GR gene and/or deficient regulation of
      its expression. The downstream components of the pathway, i.e., the GC-regulated
      genes responsible for cell death induction, have been studied by microarray-based
      comparative expression profiling, resulting in identification of a considerable
      number of GC-regulated candidate genes. Their possible function in the death
      response is, however, still undefined. One model predicts direct regulation of
      the apoptotic machinery, e.g., components of the "Bcl-2 rheostat", while a
      complementary hypothesis suggests deleterious GC effects on essential cellular
      functions, such as metabolism, production of and/or response to oxygen radicals,
      general transcription/translation, pH and volume control, etc. These regulatory
      effects may entail cell death, particularly if maintained for sufficient time
      through GR autoinduction. The latter form of cell death may occur even in the
      absence of functional apoptotic machinery (e.g., when caspases are blocked), but
      in this case appears to entail a more necrotic morphology. Taken together, GC may
      induce different types of cell death through distinct molecular pathways,
      depending on the cellular context. GC resistance might frequently result from
      defective GR expression, perhaps the most efficient means to target multiple
      antileukemic pathways.

PMID- 15860258
TI  - Sex steroid-dependent angiogenesis in uterine endometrial cancers.
AB  - In general, tumors induce angiogenic factors specific to them, which leads to
      angiogenesis with advancement. However, angiogenesis in uterine endometrial
      cancers is complicated because hormone dependency in growth also modifies the
      angiogenic potential. Therefore, anti-angiogenic therapy for tumor dormancy in
      uterine endometrial cancers must be thoroughly considered. The upstream of
      vascular endothelial growth factor (VEGF) gene conserves estrogen-responsive
      elements. Progesterone primed with estrogen induces thymidine phosphorylase (TP)
      in uterine endometrium. Sex steroid-dependent VEGF and TP are highly expressed in
      cases of early stage and well-differentiated uterine endometrial cancers, and
      basic fibroblast growth factor (bFGF) in cases of advanced and poorly
      differentiated uterine endometrial cancers. A transcriptional factor for
      angiogenesis, ETS-1, is linked to VEGF in well-differentiated uterine endometrial
      cancers, and to bFGF in poorly differentiated uterine endometrial cancers.
      Therefore, even if dedifferentiation and angiogenic switching occur due to
      advancement and long-term hormone therapy, the inhibition of ETS-1 along with
      main angiogenic factors might be an effective strategy to suppress uterine
      endometrial cancers as a novel anti-angiogenic therapy.

PMID- 15860259
TI  - Epigenetic regulation of vitamin D hydroxylase expression and activity in normal
      and malignant human prostate cells.
AB  - It was previously suggested that the 25-Vitamin-D3-1alpha-hydroxylase (CYP27B1)
      is downregulated during human prostate tumor pathogenesis while the catabolic 25
      Vitamin-D3-24-hydroxylase (CYP24) expression is increased. The latter could lead
      to resistance against the antimitotic, pro-differentiating activity of 1,25
      dihydroxycholecalciferol. Our hypothesis was that regulation of Vitamin D
      hydroxylase expression during prostate tumor progression might be under
      epigenetic control. We demonstrate by real time RT-PCR that PNT-2 human normal
      prostate cells indeed possess CYP27B1, but are practically devoid of CYP24 mRNA,
      whereas DU-145 cancer cells have constitutive expression of CYP24, and very low
      levels of CYP27B1 mRNA. Treatment of PNT-2 cells with the methylation inhibitor 5
      aza-2'-deoxycytidine together with the deacetylation inhibitor trichostatin A
      resulted in elevation of both CYP27B1 and CYP24 mRNA expression demonstrating
      that even in normal human prostate cells expression of Vitamin D hydroxylases may
      be under epigenetic control. In the DU-145 malignant cell line trichostatin A
      together with 5-aza-2'-deoxycytidine increased CYP27B1 mRNA expression to a
      smaller extent than in normal cells, however this resulted in a highly
      significant increase in 1alpha-hydroxylation capacity. This demonstrates for the
      first time that synthesis of 1,25-dihydroxycholecalciferol in human prostate
      tumors could be reinitiated by epigenetic regulators.

PMID- 15860260
TI  - p53-dependent inhibition of progestin-induced VEGF expression in human breast
      cancer cells.
AB  - VEGF, a potent angiogenic growth factor, is up-regulated in many tumors including
      human breast tumors and stimulates growth of vascular networks that support tumor
      growth and metastasis. We previously reported that natural and synthetic
      progestins (P) increased VEGF mRNA and protein levels in progesterone receptor
      (PR) containing T47-D human breast cancer cells in a PR dependent manner, but not
      in PR positive ZR-75 and MCF-7, or in PR negative MDA-MB-231 cells. This
      indicated that factors beside PR are involved in progesterone-dependent VEGF
      regulation. We, therefore, tested additional tumor cell lines reported to contain
      PR for progestin-dependent VEGF induction. Out of nine PR-positive breast tumor
      cell lines, progestins induced VEGF in three cell lines that lack wild-type p53
      (T47-D, BT-474, and HCC-1428) but not in cell lines that contained the wild-type
      p53 protein. The T47-D and BT-474 cells express mutant p53, while the p53 protein
      is absent HCC-1428 cells. The anti-progestin RU-486 blocked progestin-dependent
      induction of VEGF in T47-D and BT-474 cells but not in HCC-1428 cells. However,
      RU-486 partially blocked medroxyprogesterone acetate-dependent induction of VEGF
      in HCC-1428 cells. Estrogen receptor (ER) and PR agonists and antagonists also
      induce VEGF in HCC-1428 cells and this effect was partially blocked by anti
      estrogen ICI-182, 780. Progestin-dependent VEGF induction was completely
      inhibited by PRIMA-1-activated p53 in all cell-types, but progestin-dependent
      transcription of a progesterone-regulated minimal promoter was only partially
      inhibited. PRIMA-1 induced activation of p53 in tumor cell lines was confirmed
      with a p53-responsive p21 reporter plasmid and by detecting increased levels of
      p21 proteins in cell lysates. PRIMA-1 induced p53 protein in the HCC-1428 cells
      while levels of mutant p53 protein in T47-D and BT-474 remained unaltered.
      Progestin-dependent induction of VEGF was also inhibited by stable transfection
      of wild-type p53 in T47-D cells. These results are consistent with the hypothesis
      that wild-type p53 blocks progestin-dependent induction of VEGF in breast cancer
      cells and this may be a novel anti-angiogenic mechanism for controlling the
      growth of progestin-dependent tumors.

PMID- 15860261
TI  - Calcidiol and prostate cancer.
AB  - Epidemiological studies suggest that serum calcidiol (25(OH)-Vitamin D3) seems to
      be associated with several cancers including prostate cancer. We have made
      several experimental studies in order to clarify the mechanism(s) involved in the
      association. Calcidiol has been regarded as an inactive prohormone for
      calcitriol, which possesses the highest biological activity of the Vitamin D
      metabolites, when it is evaluated on the basis of bioactivity/nmol. However, we
      found recently that at the physiological concentration calcidiol (100-200 nM) is
      an active hormone, whereas calcitriol (1alpha,25(OH)2-Vitamin D3) (100 pM) is
      inactive in human primary prostate stromal cells. Calcidiol is able to inhibit
      cell growth and to induce or inhibit several genes including 1alpha-hydroxylase
      and 24-hydroxylase genes. This suggests that calcidiol might be an independent
      endocrine system involved in the control of cell differentiation and
      proliferation, whereas calcitriol might be mainly involved in the regulation of
      calcium and phosphorous balance. Several mechanisms may mediate the action of
      Vitamin D in the prostate. This is a review of some recent studies on the role of
      (1) Vitamin D metabolism, (2) growth factors and (3) fatty acid metabolism.

PMID- 15860262
TI  - Steroid hormone receptors as targets for the therapy of breast and prostate
      cancer--recent advances, mechanisms of resistance, and new approaches.
AB  - Surgical ovariectomy and orchiectomy, first proposed over a century ago, are
      effective in breast and prostate cancer therapy, respectively. Later, the
      discovery of steroid hormones and their nuclear receptors led to the concept that
      inhibition of steroid receptor function by an antagonist prevents tumour growth.
      While the first anti-hormones, cyproteroneacetate (CPA) and tamoxifen were found
      accidentally, deeper understanding of nuclear receptors as transcription factors
      enabled more rational, structure-activity based drug discovery. Results from a
      drug-finding program on pure anti-estrogens will be reported. These new steroidal
      anti-estrogens are highly active, pure ER-antagonists that lead to an efficient
      degradation of the estrogen receptor alpha (ERalpha) protein without any
      agonistic activity. Data obtained in preclinical tumour models in mice and rats
      showed a high potency in growth inhibition of ERalpha-positive breast cancer. In
      parallel, by comparing three independently generated anti-estrogen-resistant
      breast cancer cell lines, it was our intention to gain insight into the
      mechanisms of endocrine resistance which will allow to define new approaches for
      the treatment of endocrine-resistant breast cancer. Candidate proteins
      potentially involved in mechanisms of anti-estrogen-resistant growth of breast
      cancer cell lines were analyzed. ERalpha and progesterone receptor (PR)
      expressions were lost on the protein level in all three anti-estrogen-resistant
      cell lines, whereas binding of epidermal growth factor (EGF) and protein
      expression of epidermal growth factor receptor (EGFR) were increased. Loss of
      ERalpha expression may be linked to the acquisition of anti-estrogen resistance
      and enhanced expression of the EGFR and of members of the S100 family of Ca2+
      binding proteins may contribute to the outgrowth of resistant cells. Furthermore,
      we describe the pharmacological development of a novel, highly potent
      progesterone receptor antagonist. In rat mammary tumour models, treatment with
      the PR antagonist completely suppressed the growth of established tumours and
      prevented the development of breast tumours. Advanced prostate cancer is
      effectively treated by androgen ablation. However, this therapy becomes
      inefficient although the androgen receptor (AR) is still functionally expressed.
      One novel strategy for the treatment of advanced prostate cancer could be the
      selective inhibition of AR protein expression by anti-sense oligonucleotides or
      small interfering RNA (siRNA) molecules. Down-regulation of the human AR caused
      significant inhibition of LNCaP prostate cancer growth in vivo. Taken together,
      many promising alternatives for endocrine therapy of breast and prostate cancer
      are arising.

PMID- 15860263
TI  - The role of progesterone metabolites in breast cancer: potential for new
      diagnostics and therapeutics.
AB  - Proliferative changes in the normal breast are known to be controlled by female
      sex steroids. However, only a portion of all breast cancer patients respond to
      current estrogen based endocrine therapy, and with continued treatment nearly all
      will become unresponsive and experience relapse. Therefore, ultimately for the
      majority of breast carcinomas, explanations and treatments based on estrogen are
      inadequate. Recent observations indicate that 5alpha-pregnane and 4-pregnene
      progesterone metabolites may serve as regulators of estrogen-responsive as well
      as unresponsive human breast cancers. The conversion of progesterone to the
      5alpha-pregnanes is increased while conversion to the 4-pregnenes is decreased in
      breast carcinoma tissue, as a result of changes in progesterone metabolizing
      5alpha-reductase, 3alpha-hydroxysteroid oxidoreductase (3alpha-HSO) and 20alpha
      HSO activities and gene expression. The 5alpha-pregnane, 5alpha-pregnane-3,20
      dione (5alphaP) stimulates, whereas the 4-pregnene, 3alpha-hydroxy-4-pregnen-20
      one (3alphaHP), inhibits cell proliferation and detachment, by modulation of
      cytoskeletal and adhesion plaque molecules via the MAP kinase pathway and
      involving separate and specific plasma membrane-based receptors. The promotion of
      breast cancer appears to be related to changes in in situ concentrations of
      cancer-inhibiting and cancer-promoting progesterone metabolites. New diagnostic
      and therapeutic possibilities for breast cancer are suggested.

PMID- 15860264
TI  - Structural determinants of plant lignans for growth of mammary tumors and
      hormonal responses in vivo.
AB  - Low risk of breast cancer (BC) has been proposed to be associated with high
      intake of lignans. Some plant lignans are converted to mammalian lignans, e.g.,
      enterolactone (ENL), suggested to be the biologically active lignan forms. Until
      now, little attention has been paid to the possible biological activities of
      plant lignans, even though some plant lignans are absorbed and present in serum
      and urine. In this study, we have investigated the antitumorigenic and endocrine
      modulatory activities of different plant lignans in order to clarify the
      structure-activity relationships. 7-Hydroxymatairesinol (HMR) is [corrected]
      converted to ENL, and both HMR and ENL inhibit the growth of 7,12-dimethylbenz[a]
      anthracene (DMBA)-induced mammary cancer. Nortrachelogenin (NTG) resembles HMR,
      but has a hydroxyl group at C-8 instead of C-7 and is not converted to ENL. In
      DMBA-model, NTG showed no inhibition of tumor growth, but increased the uterine
      weight. Furthermore, life-long exposure to NTG increased uterine weight in
      immature females and ventral prostate weight in adult males. In contrast, life
      long exposure to HMR had no effects on uterine or prostate weights at any age.
      Our results indicate that a difference in the position of one hydroxyl group
      results in distinct biological responses in vivo, as well as different lignan
      metabolite profiles.

PMID- 15860265
TI  - Recent insight on the control of enzymes involved in estrogen formation and
      transformation in human breast cancer.
AB  - The great majority of breast cancers are in their early stage hormone-dependent
      and it is well accepted that estradiol (E2) plays an important role in the
      genesis and evolution of this tumor. Human breast cancer tissues contain all the
      enzymes: estrone sulfatase, 17beta-hydroxysteroid dehydrogenase, aromatase
      involved in the last steps of E2 bioformation. Sulfotransferases which convert
      estrogens into the biologically inactive estrogen sulfates are also present in
      this tissue. Quantitative data show that the 'sulfatase pathway', which
      transforms estrogen sulfates into the bioactive unconjugated E2, is 100-500 times
      higher than the 'aromatase pathway', which converts androgens into estrogens. The
      treatment of breast cancer patients with anti-aromatases is largely developed
      with very positive results. However, the formation of E2 via the 'sulfatase
      pathway' is very important in the breast cancer tissue. In recent years it was
      found that antiestrogens (e.g. tamoxifen, 4-hydroxytamoxifen), various progestins
      (e.g. promegestone, nomegestrol acetate, medrogestone, dydrogesterone,
      norelgestromin), tibolone and its metabolites, as well as other steroidal (e.g.
      sulfamates) and non-steroidal compounds, are potent sulfatase inhibitors. In
      another series of studies, it was found that E2 itself has a strong anti
      sulfatase action. This paradoxical effect of E2 adds a new biological response of
      this hormone and could be related to estrogen replacement therapy in which it was
      observed to have either no effect or to decrease breast cancer mortality in
      postmenopausal women. Interesting information is that high expression of steroid
      sulfatase mRNA predicts a poor prognosis in patients with +ER. These progestins,
      as well as tibolone, can also block the conversion of estrone to estradiol by the
      inhibition of the 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD-1). High
      expressison of 17beta-HSD-1 can be an indicator of adverse prognosis in ER
      positive patients. It was shown that nomegestrol acetate, medrogestone,
      promegestone or tibolone, could stimulate the sulfotransferase activity for the
      local production of estrogen sulfates. This is an important point in the
      physiopathology of this disease, as it is well known that estrogen sulfates are
      biologically inactive. A possible correlation between this stimulatory effect on
      sulfotransferase activity and breast cancer cell proliferation is presented. In
      agreement with all this information, we have proposed the concept of selective
      estrogen enzyme modulators (SEEM). In conclusion, the blockage in the formation
      of estradiol via sulfatase, or the stimulatory effect on sulfotransferase
      activity in combination with anti-aromatases can open interesting and new
      possibilities in clinical applications in breast cancer.

PMID- 15860266
TI  - Are aromatase inhibitors superior to antiestrogens?
AB  - Aromatase inhibitors (AIs) have been in use to treat metastatic breast cancer for
      over 25 years. Recently potent and specific AIs have been introduced, which,
      because of their low toxicity profile, are being used in the adjuvant and
      neoadjuvant situation and also for the prevention of breast cancer. The two non
      steroidal AIs, anastrozole and letrozole, and the steroidal AI, exemestane, have
      all shown superiority to tamoxifen as first-line treatment for advanced breast
      cancer. Interestingly, the oestrogen receptor downregulator, fulvestrant, was
      shown to be equivalent to anastrozole when compared as second-line therapy after
      the failure of tamoxifen. The first adjuvant AI trial began in 1996 and recruited
      over 9000 patients (ATAC trial). Anastrozole was compared with tamoxifen and a
      combination of the two drugs. There were no significant differences between
      tamoxifen and the combination. However, anastrozole showed about a 20%
      improvement in disease-free survival in ER+ disease compared with the other
      treatments. An overall survival analysis will be reported later this year. Two
      trials have compared 5 years of tamoxifen with 2-3 years of tamoxifen, followed
      by 2-3 years of AI (one trial (ITA) used anastrozole and another (intergroup)
      exemestane). Both trials show a disease-free advantage for the switch to AI. In
      another study (MA17) 5 years of tamoxifen was followed by a randomisation to
      letrozole or placebo and showed a significant disease-free advantage to the AI.
      Both letrozole and anastrozole show superiority to tamoxifen when used as a
      neoadjuvant therapy. Anastrozole significantly reduced contralateral breast
      cancer compared with tamoxifen, and this has led to two prevention trials: one in
      women at risk comparing anastrozole with placebo and the other after excision of
      DCIS comparing anastrozole with tamoxifen (IBIS II). The NCI Canada has also just
      initiated a trial of exemestane for prevention. Nearly all data available
      indicate that AIs are superior to tamoxifen. The important question is whether
      survival is improved when they are used as adjuvant therapy?

PMID- 15860267
TI  - Reversal of tamoxifen resistant breast cancer by low dose estrogen therapy.
AB  - Currently, the standard of care for estrogen receptor (ER)-positive breast cancer
      is 5 years of tamoxifen (TAM) or an aromatase inhibitor (AI) such as anastrozole.
      New studies indicate that extending antiestrogen therapy beyond 5 years with
      sequential regimens will improve disease-free survival. Based on the emerging
      concept that longer therapies are better, we have developed sequential models of
      tamoxifen-resistant breast cancer in vivo to mimic the clinical scenario of long
      term antiestrogen therapy. The goal of the current study was to investigate the
      consequences of long-term treatment with tamoxifen on the growth of breast tumors
      in athymic mice. The results demonstrate that there are distinct phases of
      resistance to tamoxifen that correlate with time of treatment and expression of
      HER2/neu mRNA. In the treatment phase, 17beta-estradiol (E2) stimulated growth,
      while TAM inhibited growth of MCF-7 tumors (MCF-7E2). The withdrawal of
      treatment, mimicking the use of an AI, completely prevented growth. In Phase I
      resistance, the tumors (MCF-7TAMST) were growth-stimulated by either E2 or TAM,
      but inhibited by no treatment, fulvestrant, or E2 + fulvestrant. Phase II
      resistant tumors (MCF-7TAMLT) were treated for more than 5 years and growth
      stimulated by TAM. However, no treatment, fulvestrant, or E2 completely inhibited
      growth. Interestingly, the few tumors (MCF-7TAMLT) that survived in response to
      E2 were robustly re-stimulated by E2 after transplantation into new generations
      of athymic mice. These E2-stimulated tumors (MCF-7TAME) were inhibited by TAM in
      a dose-dependent similar to their parental tumors (MCF-7E2). In addition, the MCF
      7TAME tumors were inhibited by either no treatment or fulvestrant. HER2/neu and
      HER3 mRNAs were over-expressed in TAM-stimulated MCF-7TAMLT tumors and remained
      high in E2-stimulated MCF-7TAME tumors. The data indicate that complete reversal
      of resistance to TAM can be achieved with the use of low dose E2 therapy. Also,
      these data suggest that over-expression of HER2/neu alone is insufficient to
      predict resistance to TAM. Based on the results, we suggest using an alternating
      treatment regimen, cycling antiestrogen with estrogen therapy to avoid drug
      resistance.

PMID- 15860268
TI  - Growth factor signalling networks in breast cancer and resistance to endocrine
      agents: new therapeutic strategies.
AB  - Recent evidence demonstrates that growth factor networks are highly interactive
      with the estrogen receptor (ER) in the control of breast cancer growth and
      development. As such, tumor responses to anti-hormones are likely to be a
      composite of the ER and growth factor inhibitory activity of these agents, with
      alterations/aberrations in growth factor signalling providing a mechanism for the
      development of anti-hormone resistance. In this light, the current article
      focuses on illustrating the relationship between growth factor signalling and
      anti-hormone failure in our in-house tumor models of breast cancer and describes
      how we are now beginning to successfully target their actions to improve the
      effects of anti-hormonal drugs and to block aggressive disease progression.

PMID- 15860269
TI  - Estrogen actions and in situ synthesis in human vascular smooth muscle cells and
      their correlation with atherosclerosis.
AB  - Various epidemiological studies have demonstrated a relatively low incidence of
      cardiovascular events in premenopausal women and its marked increment after
      menopause. In addition, estrogens have been postulated to exert direct anti
      atherogenic effects via binding to estrogen receptors (ERs) in vascular smooth
      muscle cells (VSMCs). However, not all postmenopausal women develop
      atherosclerosis despite decreased levels of serum estrogen. Therefore, it is
      considered important to examine the status of estrogen metabolism in situ and of
      ER expression in the human cardiovascular system. Estrone sulfate (E1S) is a
      major circulating plasma estrogen that is converted into the biologically active
      estrogen, estrone (E1) by steroid sulfatase (STS). E1 is also sulfated and
      reverted into E1S by estrogen sulfotransferase (EST). These two enzymes have
      recently been shown to play important roles in the in situ estrogen actions of
      estrogen-dependent human tissues. STS and EST, however, have not been studied in
      detail in the human vascular system associated with atherosclerotic changes.
      Therefore, the relative abundance of STS- and EST-immunoreactive protein and mRNA
      expression in human aorta were evaluated using immunohistochemistry and reverse
      transcription followed by quantitative polymerase chain reaction in addition to
      enzyme activity. Furthermore, we evaluated the relative abundance of messenger
      RNA (mRNA) of both ER subtypes (ERalpha and ERbeta) in the human aorta using
      reverse transcription followed by quantitative polymerase chain reaction (RT
      qPCR), as well as the immunoreactivity of both ERs in VSMCs of human
      atherosclerotic lesions. STS expression levels were found to be significantly
      higher in the VSMCs obtained from female aortas with mild atherosclerotic changes
      than in those with severe atherosclerotic changes and in male aortas regardless
      of atherosclerotic changes. EST expression levels in the VSMCs of these aortas,
      however, were significantly higher in female aortas with severe atherosclerotic
      changes and in male aortas than in female aortas with mild atherosclerotic
      changes. In addition, the number of ERalpha and/or ERbeta double positive cells
      in the neointima was higher in female aortas with a mild degree of
      atherosclerosis than in female aortas with severe atherosclerosis. They indicate
      that both abundance of these estrogen-metabolizing enzymes in female aorta and
      relative levels of ER in VSMCs of female neointima may be associated with the
      status of atherosclerotic changes.

PMID- 15860270
TI  - Quantitative appreciation of steroidogenic gene expression in mouse tissues: new
      roles for type 2 5alpha-reductase, 20alpha-hydroxysteroid dehydrogenase and
      estrogen sulfotransferase.
AB  - We have recently developed an improved method for the RealTime PCR quantification
      of reversed transcribed mRNA (Q_RTPCR) that allows to obtain absolute mRNA
      expression levels with high sensitivity and accuracy. Using this Q_RTPCR method
      to assess the mRNA expression levels of genes encoding steroidogenic enzymes in
      male and female mouse tissues allows us to gain quantitative appreciation of the
      function of these genes. We could thus identify the existence of two types of
      steroidogenic tissues: those of classical endocrine glands such as the testis,
      ovary and adrenals which deliver steroids into the circulation, and in which
      millions of copies/mug total RNA are detected, and those of peripheral intracrine
      tissues where steroids are synthesized locally and exert their action at the site
      where they are produced (prostate, uterus, etc.), and in which the expression
      level of steroidogenic enzymes is much lower. We also observed an abnormally high
      expression levels of type 2 5alpha-reductase and 20alpha-HSD in the male and
      female adrenals, respectively, thus indirectly suggesting new roles for these sex
      specific enzymes. On the other hand estrogen sulfotransferase, the enzyme that
      inactivates estrogen, has been found selectively expressed in male tissues, thus
      suggesting a role for this enzyme to protect male-specific tissues against
      estrogenic activity.

PMID- 15860271
TI  - Enzymes as modulators in malignant transformation.
AB  - Experimental data suggest that sex steroids have a role in the development of
      breast and prostate cancers. The biological activity of sex steroid hormones in
      target tissues is regulated by several enzymes, including 17beta-hydroxysteroid
      dehydrogenases (17HSD). Changes in the expression patterns of these enzymes may
      significantly modulate the intracellular steroid content and play a
      pathophysiological role in malignant transformation. To further clarify the role
      of 17HSDs in breast cancer, we analyzed the mRNA expressions of the 17HSD type 1,
      2, and 5 enzymes in 794 breast carcinoma specimens. Both 17HSD type 1 and 2 mRNAs
      were detected in normal breast tissue from premenopausal women but not in
      specimens from postmenopausal women. Of the breast cancer specimens, 16% showed
      signals for 17HSD type 1 mRNA, 25% for type 2, and 65% for type 5. No association
      between the 17HSD type 1, 2, and 5 expressions was detected. The patients with
      tumors expressing 17HSD type 1 mRNA or protein had significantly shorter overall
      and disease-free survival than the other patients. The expression of 17HSD type 5
      was significantly higher in breast tumor specimens than in normal tissue. The
      group with 17HSD type 5 overexpression had a worse prognosis than the other
      patients. Cox multivariate analyses showed that 17HSD type 1 mRNA, tumor size,
      and ERalpha had independent prognostic significance. Using an LNCaP prostate
      cancer cell line, we developed a cell model to study the progression of prostate
      cancer. In this model, androgen-sensitive LNCaP cells are transformed in culture
      conditions into more aggressive, androgen-independent cells. The model was used
      to study androgen and estrogen metabolism during the transformation process. Our
      results indicate that substantial changes in androgen and estrogen metabolism
      occur in the cells during the process. A remarkable decrease in oxidative 17HSD
      activity was seen, whereas reductive activity seemed to increase. Since local
      steroid metabolism controls the bioavailability of active steroid hormones of
      target tissues, the variations in steroid-metabolizing enzymes during cancer
      progression may be crucial in the regulation of the growth and function of
      organs.

PMID- 15860272
TI  - Inhibition of 17beta-hydroxysteroid dehydrogenases by phytoestrogens: comparison
      with other steroid metabolizing enzymes.
AB  - Effects of phytoestrogens on human health have been reported for decades. These
      include not only beneficial action in cancer prevention but also endocrine
      disruption in males. Since then many molecular mechanisms underlying these
      effects have been identified. Targets of phytoestrogens comprise steroid
      receptors, steroid metabolising enzymes, elements of signal transduction and
      apoptosis pathways, and even the DNA processing machinery. Understanding the
      specific versus pleiotropic effects of selected phytoestrogens will be crucial
      for their biomedical application. This review will concentrate on the influence
      of phytoestrogens on 17beta-hydroxysteroid dehydrogenases from a comparative
      perspective with other steroid metabolizing enzymes.

PMID- 15860273
TI  - Membranal effects of phytoestrogens and carboxy derivatives of phytoestrogens on
      human vascular and bone cells: new insights based on studies with carboxy
      biochanin A.
AB  - Estradiol-17beta (E2) and some phytoestrogens induce a biphasic effect on DNA
      synthesis in cultured human vascular smooth muscle cells (VSMC), i.e.,
      stimulation at low concentrations and inhibition at high concentrations. These
      compounds also increase the specific activity of creatine kinase (CK) as well as
      intracellular Ca2+ concentration in both VSMC and human female-derived cultured
      bone cells (OBs), and stimulate ERK1/2 phosphorylation in VSMC. At least some of
      these effects are exerted via membranal binding sites (mER), as would appear from
      observations that protein-bound, membrane impermeant estrogenic complexes can
      mimic the effect of E2 on DNA synthesis, intracellular Ca2+ concentration and
      MAPK, but not on CK activity. We now extend these studies by examining the
      effects of a novel carboxy-derivative of biochanin A, 6-carboxy-biochanin A (cBA)
      in VSMC and human osteoblasts in culture. cBA increased DNA synthesis in VSMC in
      a dose-dependent manner and was able to maintain this effect when linked to a
      cell membrane impermeable protein. In VSMC both cBA and estradiol, in their free
      or protein-bound forms induced a steep and immediate rise in intracellular
      calcium. Both the free and protein-bound conjugates of cBA and estradiol
      increased net MAPK-kinase activity. Neither the stimulatory effect of cBA nor the
      inhibitory effect of estradiol on DNA synthesis in VSMC could be shown in the
      presence of the MAPK-kinase inhibitor UO126. The presence of membrane binding
      sites for both estradiol and cBA was supported by direct visualization, using
      fluorescence labeling of their respective protein conjugates, E2-BSA and cBA
      ovalbumin. Furthermore, these presumed membrane ER for estradiol and cBA were co
      localized. In cultured human osteoblasts, cBA stimulated CK activity in a dose
      related fashion, which paralleled the increase in CK induced by estradiol per se,
      confirming the estrogenic properties of cBA in human bone cells. Both the free
      and protein-bound forms of cBA elicited immediate and substantial increments in
      intracellular Ca2+, similar to, but usually larger than the responses elicited by
      estradiol per se. cBA also increased ERalpha and suppressed ERbeta mRNA
      expression in human osteoblasts. Cultured human osteoblasts also harbor membrane
      binding sites for protein-bound form of cG, which are co-localized with the
      binding sites for protein-bound estradiol. The extent to which these properties
      of the novel synthetic phytoestrogen derivatives may be utilized to avert human
      vascular and/or bone disease requires further study.

PMID- 15860274
TI  - Progestins and estrogens and Alzheimer's disease.
AB  - Sex-specific incidence rates for Alzheimer's disease (AD) are higher in women
      than men. Many fundamental researches and some clinical investigations have
      reported therapeutic and preventive effects of estrogens on AD. But WHIMS [S.A.
      Shumaker, C. Legault, S.R. Rapp, L. Thal, R.B. Wallace, J.K. Ockene, S.L.
      Hendrix, B.N. Jones IIIrd, A.R. Assaf, R.D. Jackson, J.M. Kotchen, S. Wabertheil
      Smoller, J. Wactawsk-Wende, WHIMS investigators, Estrogen plus progestin and the
      incidence of dementia and mild cognitive impairment in postmenopausal women. The
      women's health initiative memory study: a randomized controlled trial, JAMA 289
      (2003) 2651-2662], which used daily continuous hormone replacement therapy (HRT),
      reported that the hazard ratio of the HRT for probable dementia was 2.05. Effect
      of progestins, and continuous (not cyclically) HRT, even only with estrogen
      should be reconsidered. In our clinical study, conjugated equine estrogen (CEE)
      alone showed good changes of psychiatric tests for AD on the 3rd week, but
      addition of medroxyprogesterone acetate (MPA) or norethindrone since 4th week
      suppressed these tests. Using human umbilical vein epithelial cell (HUVEC),
      levonorgestrel (LNG), norethindrone acetate (NETA), MPA increased intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E
      secretin but dienogest (DNG) showed no effect. In vitro flow system, estradiol
      (E2), suppressed adhesion of white cell, but LNG, NETA, MPA increased the
      adhesions. DNG showed less effect. Non-feminizing estrogen J 861, which has
      delta8,9 double bond and straight in its structure and has less effect on sexual
      organs. J 861 has shown ameliorative effects on central nervous system (CNS)
      (increasing of cholineacetyltransferase immunoreactive cells in substantia
      innominata (SI), etc.) like E2. More investigations about progestins and
      estrogens and AD should be done.

PMID- 15860275
TI  - Comparison of the efficacy and tolerability of a new once-a-week matricial
      estradiol transdermal system (Estrapatch 40 and Estrapatch 60) with a twice week
      system.
AB  - OBJECTIVE: To compare the efficacy and tolerability of three transdermal systems
      (Estrapatch 40, Estrapatch 60 and Oesclim 50). METHODS: Multicentre, randomized,
      open, 3 parallel group study on 421 postmenopausal women presenting with at least
      35 hot flushes in the week preceding inclusion and treated for six 28-day cycles
      with either Estrapatch 40 (n = 141) or Estrapatch 60 (n = 140) once a week or
      Oesclim 50 (n = 140) twice a week, associated to oral NETA (Millligynon 2x 0.6 mg
      tablets daily) from day 15 to day 28. Hot flushes, mastodynia, bleeding, local
      skin tolerability and adhesiveness were reported on daily cards. Endometrial
      thickness and estrogens were measured before and after treatment. RESULTS:
      Efficacy was clearly established for the three devices as early as after one
      cycle of treatment, with success rates (% of women with a decrease > or = 50% of
      the number of hot flushes) over 97% from cycle 2. The three treatments were
      equivalent on this criteria, except at cycle 1 for Estrapatch 40 which was not
      equivalent to both other treatments. Incidence and severity of mastodynia,
      bleeding pattern, endometrial thickness and specific estrogen-related adverse
      events reflected a significant higher estrogenic stimulation with Oesclim 50.
      Adhesiveness was very satisfactory for the three systems. CONCLUSIONS: Estrapatch
      40 and 60 presents a better benefit/risk ratio compared to Oesclim 50. Thus
      Estrapach 40 appears to be a good choice for a first-line estrogen replacement
      therapy with the possibility to increase the dose to Estrapatch 60.

PMID- 15860276
TI  - Effects of estrogen on neuronal growth and differentiation.
AB  - Previous work from our laboratory has shown that in cultures of hypothalamic
      neurons obtained from male fetuses at embryonic day 16 the axogenic response to
      estradiol (E2) is contingent upon culture with medium conditioned by astroglia
      from a target region for hypothalamic axons. E2 also induced increased levels of
      TrkB that were necessary for the axonal growth to occur. This convergence between
      estrogenic and neurotrophic signals prompted investigation of the mitogen
      activated protein kinase (MAPK) cascade. Analysis of the temporal course of MAPK
      activation showed increased levels of phosphorylated ERK up to 60 min after E2
      exposure, with a maximal response at 5-15 min. UO126 (specific inhibitor of MEK
      1/2) blocked E2 induced axonal elongation and ERK phosphorylation, confirming the
      involvement of ERK in the neuritogenic effect of E2. The membrane impermeable
      construct E2-BSA proved as effective as free E2 to induce axon elongation,
      suggesting that E2 exerted its effect through a membrane-associated receptor.
      This possibility received additional support from experiments showing that E2-BSA
      also increased ERK phosphorylation with the same time course than E2. These
      results indicate that ERK signaling is necessary for E2 to induce axon growth and
      this activation is mediated by a membrane bound estrogen receptor.

PMID- 15860277
TI  - Assessment of human contamination of estrogenic endocrine-disrupting chemicals
      and their risk for human reproduction.
AB  - There is broad human exposure to estrogenic endocrine-disrupting chemicals
      (EDCs), but the data sets that exist are primarily for various environmental
      media such as food and water rather than the most relevant internal exposure. We
      have detected various kind of EDC contamination in humans including dioxin and
      bisphenol A (BPA) widely used for the production of plastic products. BPA was
      present in serum and follicular fluid at approximately 1-2 ng/ml, as well as in
      fetal serum and full-term amniotic fluid, confirming passage through the
      placenta. An approximately five-fold higher concentration, 8.3+/-8.7 ng/ml, was
      revealed in amniotic fluid at 15-18 weeks of gestation, compared to other fluids
      showing increased exposure at the critical developmental period in humans.
      Interestingly, serum BPA concentrations were significantly higher in normal men
      and in women with polycystic ovary syndrome (PCOS) compared with normal women
      possibly due to differences in the androgen-related metabolism of BPA. These
      findings may provide some insight into the metabolism of EDCs in human and the
      pathophysiology of endocrine disorders such as PCOS. Dioxin contamination in
      relationship to development of endometriosis is also discussed.

PMID- 15860278
TI  - Stage-specific antileishmanial activity of an inhibitor of SIR2 histone
      deacetylase.
AB  - Silent information regulator 2 (SIR2) proteins are NAD-dependant deacetylases
      found in organisms ranging from bacteria to human. In eukaryotes, these proteins
      are involved in many biological processes including transcriptional repression,
      metabolism, ageing, or apoptosis. Here, we have shown that Sirtinol, a
      commercially available inhibitor of SIR2 deacetylases, significantly inhibits the
      in vitro proliferation of Leishmania infantum axenic amastigotes in a dose
      dependent manner. This activity is stage specific since sirtinol did not affect
      the in vitro growth of parasite promastigotes. Growth arrest in amastigotes is
      associated with genomic DNA fragmentation, a process reminiscent of apoptosis.
      Interestingly parasites carrying extra copies of the LmSIR2 gene were less
      susceptible to the sirtinol mediated cell death. Altogether, these results
      constitute novel evidences that Leishmania SIR2 proteins play a role in the
      control of the parasite apoptotic phenomenon.

PMID- 15860279
TI  - Choosing the location of corneal incision based on preexisting astigmatism in
      phacoemulsification.
AB  - PURPOSE: To investigate the best location of clear-cornea incision in
      phacoemulsification, depending on preexisting corneal astigmatism. DESIGN:
      Randomized clinical trial and noncomparative interventional case series. METHODS:
      A total of 574 patients in five stages were assigned to the following incisions:
      superior or temporal (n = 89), superior (n = 141), superior or superior plus
      relaxing (n = 102), nasal or temporal (n = 156), and incisions based on applying
      conclusions of preceding and current studies (n = 86). Visual acuity, refraction,
      biomicroscopy, keratometry, and videokeratography (Fourier analysis) were
      performed before and after phacoemulsification and intraocular lens implantation
      (3.5-mm incision). main outcome measures: Corneal refractive and surface
      regularity index change between preoperative and 6-month postoperative
      examination. Visual acuity at 6 months. RESULTS: In patients without corneal
      astigmatism, corneal changes induced were greater in superior than temporal
      incision. After a superior incision (preoperative steep axis at 90 degrees), a
      shift of the axis 90 degrees away was less likely with at least 1.5 diopters of
      astigmatism. A perpendicular relaxing limbal incision decreased corneal changes.
      Nasal incision induced greater corneal change than temporal incision
      (preoperative steep axis at 180 degrees). A shift of this axis 90 degrees away
      was more likely with astigmatism < 0.75 diopters in temporal incision and < 1.25
      diopters in nasal incision. CONCLUSIONS: Superior incision is recommended with at
      least 1.5 diopters of astigmatism and steep axis at 90 degrees. Temporal incision
      is recommended with astigmatism < 1.5 diopters and steep axis at 90 degrees,
      negligible astigmatism, or astigmatism < 0.75 diopters and steep axis at 180
      degrees. Nasal incision is recommended with at least 0.75 diopters of astigmatism
      and steep axis at 180 degrees.

PMID- 15860280
TI  - Natural history of asymptomatic clinical retinal detachments.
AB  - PURPOSE: To determine the natural history of asymptomatic, clinical
      rhegmatogenous retinal detachment. DESIGN: Single observer, prospective,
      consecutive, observational case series. METHODS: Consecutive patients were
      included who were referred to the author's clinical practice with rhegmatogenous
      retinal detachment extending greater than two disk-diameters posterior to the
      equator. Patients whose eye had an intraocular procedure within the past year or
      who had a history of symptomatic retinal detachment in the fellow eye were
      excluded. Eighteen eyes of 16 patients were followed for an average of 46 months.
      The main outcome measure was progression of asymptomatic retinal detachment to
      symptomatic retinal detachment. RESULTS: None of the 18 asymptomatic, clinical,
      rhegmatogenous retinal detachments became symptomatic. The posterior margin of
      one retinal detachment slightly progressed 4 months into the study and then
      stabilized for 4 years and remained asymptomatic. CONCLUSIONS: Asymptomatic,
      clinical, rhegmatogenous retinal detachments can probably be safely observed for
      many years.

PMID- 15860282
TI  - Modified grid laser photocoagulation versus pars plana vitrectomy with internal
      limiting membrane removal in diabetic macular edema.
AB  - PURPOSE: To compare the effectiveness of pars plana vitrectomy (PPV) and removal
      of the internal limiting membrane (ILM) with modified grid laser photocoagulation
      in diabetic macular edema. DESIGN: Randomized, comparative, interventional study.
      METHODS: In this prospective study, 24 eyes of 12 patients with bilateral
      diabetic macular edema were evaluated. PPV with removal of the ILM was performed
      at random in one eye of 12 patients (ILM group), and a single session of modified
      grid laser photocoagulation was performed in the fellow eyes (grid group). Main
      outcome measures were the foveal thickness measured with optical coherence
      tomography, preoperative, and postoperative visual acuities. Mann-Whitney U and
      Wilcoxon tests were used in statistical analysis. RESULTS: All patients were
      followed up for 6 months. In the ILM group, mean foveal thickness was 439.2 +/-
      106.5 microm preoperatively and 219.8 +/- 63.2 mum postoperatively (P = .002). In
      the grid group, mean foveal thickness was 407 +/- 100.2 microm preoperatively and
      378.5 +/- 141.6 microm postoperatively (P = .433). A mean decrease in foveal
      thickness was found to be 219.4 +/- 127.6 microm in the ILM group and 28.5 +/-
      90.5 microm in the grid group (P = .001). In the ILM group, best-corrected logMAR
      visual acuity was 0.75 +/- 0.41 preoperatively and 0.53 +/- 0.41 postoperatively
      (P = .006). In the grid group, best-corrected logMAR visual acuity was 0.59 +/-
      0.27 preoperatively and 0.49 +/- 0.27 postoperatively (P = .058). Visual acuity
      improved by 2 or more lines in six eyes (50%) in the ILM group and in three eyes
      (25%) in the grid group. Visual acuity remained stable in six eyes (50%) in the
      ILM group and in nine eyes (75%) in the grid group. CONCLUSIONS: PPV with ILM
      removal appears to be more effective than a single session of modified grid laser
      photocoagulation in the treatment of diabetic macular edema. Further studies with
      a large number of patients are required for a more reliable conclusion.

PMID- 15860281
TI  - Clinical and electrophysiologic characterization of paraneoplastic and autoimmune
      retinopathies associated with antienolase antibodies.
AB  - PURPOSE: Paraneoplastic and autoimmune retinopathies are immunologically mediated
      retinal degenerations that are associated with antibodies directed against any of
      several retinal proteins, including alpha-enolase. We report the clinical and
      electrophysiological features of antienolase retinopathy in contrast to the
      features of antirecoverin retinopathy. DESIGN: Retrospective, observational case
      series. METHODS: Patients were referred for evaluation of unexplained acquired
      visual symptoms, including photopsias, and loss of visual acuity or field
      considered of possible retinal origin. Full-field and multifocal
      electroretinograms (ERGs) were performed. Sera from patients were examined for
      antiretinal antibodies by Western blot analysis using proteins extracted from
      human retinas and by immunohistochemistry; antienolase was confirmed by
      incubating patient sera with purified alpha-enolase. RESULTS: Of 87 patients with
      unexplained retinal visual symptoms associated with abnormal ERGs, 37 (43%)
      demonstrated autoantibodies to retinal antigens, including 12 against alpha
      enolase, of whom 4 had cancer. Initial visual loss was typically central and
      often asymmetric. The ERGs demonstrated mostly normal rod responses but central
      cone abnormalities (evident on multifocal ERG) and, for many, global cone
      abnormalities. Seven patients developed optic disk pallor. Corticosteroid and
      immunosuppressive therapy, when attempted, was clinically ineffective.
      CONCLUSIONS: Antienolase retinopathy is a protean autoimmune retinopathy that
      characteristically presents with cone dysfunction. The visual impairment and
      course vary from relative stability for years to slow progression with loss of
      central vision. With time, optic disk pallor can evolve, presumably from
      attrition of ganglion cells.

PMID- 15860283
TI  - Relation between reduction of foveal thickness and visual acuity in diabetic
      macular edema treated with intravitreal triamcinolone.
AB  - PURPOSE: To evaluate the correlation between improvement in visual acuity and the
      reduction of foveal thickness after a single intravitreal injection of 4 mg of
      triamcinolone in diabetic macular edema. DESIGN: Prospective, interventional,
      nonrandomized clinical trial. METHOD:  PATIENTS: In a prospective study 24 eyes
      with diabetic macular edema were treated with an intravitreal injection of 4 mg
      of triamcinolone acetonide. MAIN OUTCOME MEASURES: Best-corrected logMAR visual
      acuity and optical coherence tomography were performed at baseline and 3 months
      after the treatment. RESULTS: At baseline the average foveal thickness was 462 +/
      154 microm (95% confidence interval, 397-527 microm) and at 3 months 257 +/-114
      microm (95% confidence interval, 209-305 microm) (P < .0001). The best-corrected
      logMAR average visual acuity was 60.5 +/- 10.5 (95% confidence interval, 56.0
      65.0) ETDRS letters at baseline compared with 65.5 +/- 11.1 (95% confidence
      interval, 60.8-70.1) 3 months after the injection (P = .0001). There was no
      correlation between the improvement in visual acuity and the reduction of foveal
      thickness (r = 0.054, P = .8), but there was a correlation between reduction in
      foveal thickness and the age of the patients (r = 0.53, P = .008). CONCLUSION: A
      single injection of 4 mg of intravitreal triamcinolone acetonide effectively
      reduces the foveal thickness in diabetic macular edema and improves visual
      acuity, but there does not appear to be a strong correlation between the
      reduction of foveal thickness and the improvement in visual acuity.

PMID- 15860284
TI  - Optical coherence tomography assessment of the vitreoretinal relationship in
      diabetic macular edema.
AB  - PURPOSE: To study the vitreoretinal relationship in diabetic patients with and
      without diabetic macular edema (DME) using optical coherence tomography. DESIGN:
      Retrospective case-control study. METHODS: setting: Institutional practice.
      patients: Thirty-five consecutive diabetic patients (49 eyes) with DME and 35 sex
      and age-matched diabetic control patients without DME (49 eyes). observation
      procedure: All patients had Early Treatment Diabetic Retinopathy Study visual
      acuity measurement and biomicroscopic examination of the vitreoretinal interface.
      OCT was performed to obtain cross-sectional images of the vitreoretinal interface
      of the macular region. Posterior vitreous detachment (PVD) was staged from 0 to 3
      as follows: stage 0: absence of PVD; stage 1: perifoveolar PVD with foveolar
      attachment; stage 2: incomplete PVD with residual attachment to the optic nerve;
      and stage 3: complete PVD. Retinal thickness was measured using OCT mapping
      software in all cases. main outcome measures: Prevalence of the different PVD
      stages in both groups of eyes. RESULTS: The mean age of the patients was 60 years
      in both groups. Of the eyes with macular edema, 19 (38.8%) were stage 0, 26
      (53.0%) stage 1, 1 (2.0%) was stage 2, and 3 (6.2%) were stage 3. In eyes without
      DME, the corresponding figures were, respectively, 34 (69.4%), 11 (22.4%), 1
      (2.0%), and 3 (6.2%). The prevalence of perifoveolar PVD with foveolar attachment
      was significantly higher in the group of eyes with DME (P =.006). CONCLUSIONS:
      These results show the high prevalence of perifoveolar PVD with foveolar
      attachment in diabetic patients with macular edema. Even though PVD is not the
      main factor involved in the pathogenesis of DME, perifoveolar PVD may have a role
      in the development of this complication.

PMID- 15860285
TI  - Stage 3 macular hole: role of optical coherence tomography and of B-scan
      ultrasonography.
AB  - PURPOSE: To analyze the various aspects of Stage 3 macular hole with optical
      coherence tomography (OCT) and B-scan ultrasonography. DESIGN: Observational case
      series. METHODS: Patients referred for full-thickness macular hole were
      prospectively screened with OCT and B-scan ultrasonography. OCT examination
      analyzed the diameter of the hole, the posterior hyaloid, the surrounding retina,
      and the inconstant presence of a pseudo-operculum. B-scan ultrasonography
      permitted the distinction between stage 3 and stage 4 holes, based on the
      detachment of the posterior hyaloid. RESULTS: The study included 62 eyes with
      stage 3 holes. On OCT, the typical aspect with a hyaloid detached from the
      macular area was observed in 37% of the eyes (group 3C). In 42% of the eyes
      (group 3B), a focal adherence was visible at the margin of the hole, as in stage
      2 macular hole, but the hole was long-standing, large, and noneccentric. In 21%
      of the eyes, the hyaloid was not visible anterior to the retina but was still
      adherent to it (group 3A). In the absence of B-scan ultrasonography, these OCT
      features could be confused with a stage 4 macular hole. No difference in the size
      of the hole was observed between subgroups. CONCLUSION: OCT can show various
      aspects of stage 3 macular holes. B-scan ultrasonography was useful for assessing
      the location of the posterior hyaloid and to distinguish stage 3 from stage 4
      macular holes. These features may provide additional information on the
      pathogenesis of macular hole and may have therapeutic implications.

PMID- 15860286
TI  - Comparing age-related macular degeneration phenotype in probands from singleton
      and multiplex families.
AB  - PURPOSE: To compare age-related macular degeneration (AMD) phenotype between
      probands in singleton and multiplex families to determine whether data from these
      two groups may be combined for consolidated genetic analyses. DESIGN:
      Retrospective case-control study. METHODS: Individuals 55 years of age or older
      with AMD were identified. Complete histories and examinations were recorded, 35
      mm fundus photographs obtained, and macular findings graded. Detailed information
      was recorded, including the presence of extramacular and peripheral drusen,
      peripheral reticular pigmentary change, posterior vitreous detachment, and iris
      color. Comparisons were performed between probands from singleton and multiplex
      families. RESULTS: There was no statistically significant difference in grade
      between the 411 singleton and 125 multiplex probands (P = .52), and the
      distribution of grades was similar between the two groups. No statistically
      significant difference was found between proband groups with respect to the
      presence or extent of small (P = .48), intermediate (P = .72), and large drusen
      (P = .74) and retinal pigment epithelium hyper- (P = .76) and hypopigmentation (P
      = .55); in the presence or grade of peripheral reticular pigment change; the
      presence of geographic atrophy in exudative disease, extramacular drusen, or
      posterior vitreous detachment; lens status; iris color; visual acuity;
      intraocular pressure; optic nerve cupping; and body mass index. A statistically
      significant difference between the two groups was noted in the presence of
      peripheral drusen (P = .0001). CONCLUSIONS: Singleton and multiplex AMD probands
      share a similar phenotype. This suggests that multiplex and singleton data can be
      combined for consolidated genetic analyses.

PMID- 15860287
TI  - Repeat keratoplasty for correction of high or irregular postkeratoplasty
      astigmatism in clear corneal grafts.
AB  - PURPOSE: To evaluate the functional results of repeat penetrating keratoplasty in
      clear corneal grafts with high/irregular postkeratoplasty astigmatism. DESIGN:
      Retrospective, longitudinal, single-center, consecutive clinical case series.
      METHODS: We studied 17 eyes (16 keratoconus, 1 Fuchs' dystrophy) of 16 patients
      (age, 54.9 +/- 12.6 years). They were treated with repeat PK, performed using the
      193-nm Zeiss-Meditec MEL-60 excimer laser using round metal masks (diameter, 7.5
      8.0 mm), and employing double running sutures. main outcome measures: Subjective
      refractometry, standard keratometry, and corneal topography (Tomey TMS-1) were
      used to assess best-corrected visual acuity (BCVA), spherical equivalent (SEQ),
      keratometric and topographic central corneal power (CP), refractive, keratometric
      and topographic astigmatism, surface regularity index (SRI), surface asymmetry
      index (SAI), and potential visual acuity (PVA) preoperatively, before and after
      first suture removal (1.1 year), and after second suture removal (1.8 years).
      RESULTS: Visual acuity improved significantly (BCVA from 0.2-0.5, P = .04 or
      better) for all postoperative measurements. CP decreased significantly, but SEQ
      did not change. All measures of astigmatism and SRI and SAI values showed
      postoperative improvement with sutures in place; however, astigmatism increased
      significantly after second suture removal. CONCLUSIONS: With all-sutures-in, BCVA
      and astigmatism improve significantly after repeat PK for high/irregular
      astigmatism. However, to present significant increase in astigmatism, final
      suture removal should be postponed as long as possible in such eyes.

PMID- 15860288
TI  - Longer-term outcomes of transconjunctival sutureless 25-gauge vitrectomy.
AB  - PURPOSE: To report longer-term outcomes in eyes undergoing 25-gauge
      transconjunctival sutureless vitrectomy. DESIGN: Retrospective, noncomparative,
      case series. METHODS: Chart review of the initial 45 consecutive patients (45
      eyes) that underwent TSV by one surgeon (T.S.H.) for idiopathic epiretinal
      membrane (n = 15), refractory diabetic macular edema (n = 11), idiopathic macular
      hole (n = 10), and nonclearing vitreous hemorrhage (n = 9). All patients had at
      least 6-month follow-up. Main outcome measures included visual acuity (VA),
      intraocular pressure, intraoperative complications, and postoperative
      complications. RESULTS: Mean follow-up was 13 months (range 6 to 25 months). Mean
      overall preoperative VA vs last postoperative VA was 20/229 and 20/65,
      respectively (P < .0001). Statistically significant VA improvement was seen for
      each patient subgroup. Mean preoperative intraocular pressure was 16.9 mm Hg
      (range 10-26 mm Hg). On postoperative day 1, week 1, and week 4, median
      intraocular pressure was 14.6 mm Hg (range 8-17 mm Hg), 17.6 mm Hg (range 8-38 mm
      Hg), and 17.7 mm Hg (range 9-33 mm Hg), respectively. No intraoperative
      complications occurred. Postoperative complications were 1 inferior retinal
      detachment (2.2%) 4 weeks after macular hole repair, 1 macular hole (2.2%) 6
      months after epiretinal membrane peel, and 23 worsening cataracts in 29 phakic
      eyes (79.3%). CONCLUSIONS: Less surgically complex vitreoretinal pathology may be
      successfully repaired with TSV. After a mean follow-up of more than 1 year,
      minimal complications were seen, and none was specifically related to the
      sutureless nature of the procedure.

PMID- 15860289
TI  - Nocardia endophthalmitis after cataract surgery: clinicomicrobiological study.
AB  - PURPOSE: To analyze the clinical presentation, microbiological profile, and
      treatment outcome in cases of nocardial endophthalmitis after cataract surgery.
      DESIGN: Retrospective, observational case series. METHODS: setting: Tertiary
      referral hospital. patients: Retrospective analysis of 24 cases of culture-proven
      exogenous nocardial endophthalmitis following cataract surgery between January
      2000 and December 2003. main outcome measures: Visual acuity and anatomic
      outcome. RESULTS: Visual outcome was poor in most patients, with 79% (19/24) of
      patients obtaining a final visual acuity of hand motions or worse and 46% (11/24)
      of patients with no light perception. Initial presenting visual acuity was
      strongly associated with final visual outcome (P = .0026). There was a
      statistically significant trend favoring better visual outcome in patients who
      presented early after the onset of symptoms (P = .01). The majority of the eyes
      (23/24) had an early onset with predominantly anterior segment involvement. Wound
      infection was noted in 46% (11/24) of the patients at presentation. Clinical
      features included scleral abscess, cotton ball exudates in the anterior chamber,
      fluffy exudates on the corneal endothelium, nodular exudates on the iris, and
      hypopyon. Among the specimens cultured, the highest positivity was seen with the
      anterior chamber aspirate (15/16 = 93.75%), which was significantly higher than
      the vitreous aspirate cultured (1/22 = 4.54%) (P = .001). CONCLUSION: Nocardia
      endophthalmitis after cataract surgery is an aggressive disease with poor visual
      prognosis. Early diagnosis and treatment with good visual acuity at presentation
      may be associated with better visual outcome.

PMID- 15860290
TI  - Experience with the baerveldt glaucoma implant in the management of pediatric
      glaucoma.
AB  - PURPOSE: To report the clinical outcome in 48 eyes of 48 children who received a
      Baerveldt glaucoma implant (BGI) for the management of pediatric glaucoma.
      DESIGN: Retrospective, noncomparative case series. METHODS: The medical records
      of all patients with pediatric glaucoma who underwent a BGI at two tertiary care
      referral centers in Los Angeles between 1990 and 1999 were reviewed. Intraocular
      pressure (IOP), intraoperative and postoperative complications, number of
      glaucoma medications, visual acuity, and pre- and postoperative corneal diameter
      and axial length were collected from patient records. Criteria for success were
      IOP between 6 and 21 mm Hg with or without glaucoma medications, no need for
      further glaucoma surgery, the absence of visually threatening complications, and
      some residual vision (minimum visual acuity of light perception). RESULTS: The
      study included 48 eyes from 48 patients aged 16 years and younger (mean age 4.1
      years). Mean preoperative IOP was 31.2 +/- 25.7 mm Hg, and mean postoperative IOP
      was 16.4 +/- 4.9 mm Hg. Cumulative probability of success (based on the Kaplan
      Meier survival curve) was 95% at 6 months, 90% at 1 year, 84% at 2 years, 74% at
      36 months, and 58% at 48 months. On average, the BGIs were successful for a mean
      period of 5.6 years (67.7 months). Overall, 11 eyes failed, with the causes being
      uncontrolled IOP (eight eyes), retinal detachment (two eyes), and no light
      perception (one eye). CONCLUSIONS: Baerveldt glaucoma implants can be a safe and
      effective treatment modality for the management of pediatric glaucoma refractive
      to medical therapy.

PMID- 15860291
TI  - The use of acetazolamide in idiopathic intracranial hypertension during
      pregnancy.
AB  - PURPOSE: To describe the pregnancy outcomes after the use of acetazolamide in
      pregnant patients with idiopathic intracranial hypertension (IIH). DESIGN:
      Observational case series. METHODS: setting: Two tertiary care academic neuro
      ophthalmology units. patient population: Patients with IIH treated with
      acetazolamide. observation procedure: Documentation of pregnancy outcome. main
      outcome measures: Normal pregnancy, fetal loss, or congenital malformation.
      RESULTS: Twelve patients were treated with acetazolamide for IIH during
      pregnancy, and there were no adverse pregnancy outcomes. A critical review of the
      English language literature on the subject failed to demonstrate any convincing
      evidence for any adverse effect on pregnancy for acetazolamide. CONCLUSIONS:
      Acetazolamide at high doses may produce birth defects in animals, but there is
      little clinical or experimental evidence to support any adverse effect of the
      drug on pregnancy outcomes in humans. If the clinical situation warrants the use
      of acetazolamide in IIH, then the drug probably can be offered after appropriate
      informed consent.

PMID- 15860292
TI  - Intravitreal triamcinolone acetonide for cystoid macular edema in nonischemic
      central retinal vein occlusion.
AB  - PURPOSE: The effectiveness of intravitreal triamcinolone acetonide in the
      treatment of cystoid macular edema from central retinal vein occlusion (CRVO) was
      investigated. DESIGN: A noncomparative, prospective, interventional case series.
      METHODS: In a clinical practice, 18 patients were enrolled with nonischemic CRVO
      and cystoid macular edema. Two milligrams of triamcinolone acetonide were
      injected into the vitreous of only one eye from each patient. The outcome
      measures were 1-mm mean central retinal thickness on optical coherence tomography
      and visual acuity. RESULTS: Mean duration of symptoms before surgery was 2 months
      (SD, 1.3 months). Ten patients required repeated injections for recurrent cystoid
      macular edema (mean, 1.8 injections). Mean visual acuity significantly improved
      from 20/300 to 20/166 (P = .007) at 1 month, 20/100 (P = .0005) at 2 months,
      20/130 (P = .007) at 3 months, and 20/150 (P = .02) at 6 months but deteriorated
      again to 20/270 (not significant) at 12 months. There was a significant
      improvement in retinal thickness from presentation 518 microm, to 363 microm (P =
      .03) at 1 month, 304 microm (P = .04) at 2 months, and 353 microm (P = .01) at 3
      months but not from presentation at 6 months (mean, 383 microm) and 12 months
      (mean, 406 microm). Eleven patients suffered intraocular pressure rises requiring
      intervention. Intravitreal triamcinolone acetonide did not prevent collateral
      circulation formation, which was seen in 10 patients. CONCLUSION: Intravitreal
      corticosteroid injection is very effective in reversing cystoid macular edema and
      improving visual acuity in recent-onset nonischemic CRVO in the first 6 months,
      but this is unfortunately not sustained at 1 year.

PMID- 15860293
TI  - The successful treatment of gatifloxacin-resistant Staphylococcus aureus
      keratitis with Zymar (gatifloxacin 0.3%) in a NZW rabbit model.
AB  - PURPOSE: To determine whether gatifloxacin-resistant S. aureus (Gat-R-Sa)
      keratitis could be successfully treated with topical Zymar (gatifloxacin 0.3%) in
      a rabbit model. DESIGN: Experimental animal study. METHODS: Two separate studies
      were performed each using two clinical isolates of Gat-R-Sa, with MICs of 12 and
      64 mug/ml to gatifloxacin. Study 1 consisted of four treatment groups (Zymar,
      Quixin [levofloxacin 0.5%], Ciloxan [ciprofloxacin 0.3%], and saline). Study 2
      consisted of Zymar, cefazolin 50 mg/ml, vancomycin 50 mg/ml, and saline. Rabbits
      were infected intrastromally with 2,000 cfu in both eyes. Topical therapy began
      after four hours, every 15 minutes for 5 hours. After therapy, the eyes were
      graded for clinical signs of infection (blepharitis, conjunctivitis, iritis,
      corneal edema, and corneal infiltrates), and the corneas were homogenized to
      determine viable bacterial counts. RESULTS: Study 1: for both isolates, Zymar
      treated eyes demonstrated significantly lower clinical scores compared with
      Ciloxan and saline, and significantly decreased the number of viable bacteria
      recovered compared with all groups. Study 2: for both isolates, Zymar and
      cefazolin demonstrated significantly lower clinical scores compared with
      vancomycin and saline. Zymar, cefazolin, and vancomycin significantly decreased
      the number of viable bacteria recovered compared with the saline control.
      CONCLUSIONS: We demonstrated the "Proof of Principle" that in vitro antibiotic
      resistance, based on CLSI standards, does not always correlate with in vivo
      treatment failure in the eye. An aggressive treatment regimen with Zymar appears
      to overcome in vitro resistance, resulting in the successful treatment of Gat-R
      Sa infections in the NZW rabbit keratitis model.

PMID- 15860294
TI  - the impact of definition of primary open-angle glaucoma on the cross-sectional
      assessment of diagnostic validity of Heidelberg retinal tomography.
AB  - PURPOSE: To evaluate the impact of different definitions of primary open angle
      glaucoma (POAG) on assessment of the diagnostic validity of Heidelberg Retinal
      Tomography (HRT). DESIGN: Retrospective, cross-sectional study. METHODS: A search
      of medline (1992-2003) led to the retrieval of 181 papers containing definitions
      of POAG, including the eight visual field (VF)-based definitions used for this
      study. A sample of 193 normal subjects, 222 patients with suspected POAG, and 103
      with POAG underwent HRT and the 24 II Humphrey VF examinations to assess the
      diagnostic validity of HRT. POAG was defined on the basis of Glaucoma Hemifield
      Test (GHT) "out of normal limits" associated with corrected pattern standard
      deviation (CPSD) > 2 dB and intraocular pressure (IOP) > or =22 mm Hg. The VFs
      were re-analyzed and categorized according to the other eight definitions of
      POAG: IOP formed part of all the definitions, whereas the appearance of the optic
      disk did not. The sensitivity and specificity of each scenario were calculated by
      standard procedures. RESULTS: The definitions of POAG found in the literature
      included 17 IOP criteria, more than 15 optic disk criteria, and more than 30 VF
      criteria. The sensitivity of HRT ranged from 0.51 to 0.80, and its specificity
      from 0.94 and 0.95 when the patients with suspected POAG were excluded;
      diagnostic validity was much lower and still variable when the POAG suspects were
      included with the normal or the POAG groups. CONCLUSIONS: The most commonly used
      VF-based definitions of POAG led to substantial differences in the sensitivity
      and specificity of HRT when using the same large sample of normal subjects and
      POAG patients. A standard definition of POAG is needed to make diagnostic
      investigations more accurate and comparable.

PMID- 15860295
TI  - Heavy metal concentrations in human eyes.
AB  - PURPOSE: To measure the concentration of toxic heavy metals in the fluids and
      tissues of human eyes. DESIGN: Laboratory investigation. METHODS: Thirty autopsy
      eyes of 16 subjects were dissected to obtain the aqueous, vitreous, lens, ciliary
      body, retina, and retinal pigment epithelium/choroid. Concentrations of lead,
      cadmium, mercury, and thallium in ocular tissues, ocular fluids, and blood were
      determined using an inductively coupled plasma-mass spectrometer and expressed as
      ng/g. Heavy metal concentrations in ocular tissues were compared using a paired t
      test. RESULTS: Lead and cadmium were found in all of the pigmented ocular tissues
      studied, concentrating to the greatest extent in the retinal pigment
      epithelium/choroid (mean, 432 +/- 485 ng/g and 2,358 +/- 1,522 ng/g). Cadmium was
      found in the retina in all eyes (mean, 1,072 +/- 489 ng/g) whereas lead was found
      in the retina in 9 (30%) of 30 eyes (mean, 53 +/- 54 ng/g). Trace concentrations
      of lead and cadmium were detected in the vitreous (mean, 0.5 +/- 1.0 ng/dl and 19
      +/- 29 ng/dl), lens (mean, 13 +/- 18 ng/g and 20 +/- 18 ng/g), and blood (mean,
      0.5 +/- 1.2 mug/dl and 3.1 +/- 4.1 mug/l) but were not detected in the aqueous.
      Mercury and thallium were not detected in any ocular tissues or fluids or in the
      blood. CONCLUSIONS: Lead and cadmium accumulate in human ocular tissues,
      particularly in the retinal pigment epithelium and choroid. The potential ocular
      toxicity of these heavy metals and their possible role in eye disease requires
      further study.

PMID- 15860296
TI  - Screening for mutations in CYP4V2 gene in Japanese patients with Bietti's
      crystalline corneoretinal dystrophy.
AB  - PURPOSE: To describe the clinical and genetic characteristics of six Japanese
      families with Bietti's crystalline corneoretinal dystrophy (BCD). DESIGN: Case
      reports and results of DNA analysis. METHODS: Mutation screening was performed on
      six unrelated patients with BCD by direct sequencing. The clinical features were
      characterized by the visual acuity, slit-lamp biomicroscopy, electroretinography,
      fluorescein angiography, and kinetic visual field testing. RESULTS: An identical
      IVS6 to 8delTCATACAGGTCATCGCG/insGC mutation in the CYP4V2 gene was identified in
      five of the patients with BCD; the sixth patient had a novel Trp340X mutation in
      the CYP4V2 gene. Three patients showed crystalline-like deposits at the limbus by
      specular microscopy. Ophthalmic findings of all patients had a rapid progression
      after age 50 years. CONCLUSIONS: Our findings suggest that the IVS6 to
      8delTCATACAGGTCATCGCG/insGC mutation is a common mutation in Japanese patients
      with BCD. Although phenotypic variability was found, the natural course was
      almost the same in all of our patients.

PMID- 15860297
TI  - Improving the reporting of clinical case series.
AB  - PURPOSE: To describe common errors in the analyses and data presentation of a
      clinical case series and to suggest simple solutions. DESIGN: Instructional
      examples. METHODS: Problems with commonly used data analysis and reporting
      techniques in clinical case series are described using both theoretical examples
      and those from the literature. RESULTS: An analysis reporting the proportion of a
      series of patients with variable follow-up does not adequately account for the
      differential follow-up among patients and is a potentially misleading way to
      present data. Instead, the proportion of patients at presentation (or study
      entry) and the rate during follow-up should be reported. Similarly, an analysis
      in which the final visual acuity of a series of patients with variable follow-up
      is reported does not adequately account for the effect of time and also may be
      misleading. Reporting of the rates of visual acuity events during follow-up
      (e.g., falling below a specified threshold, such as 20/50 or worse) is preferred.
      Alternatively, when there is nearly complete follow-up, reporting the
      distribution of visual acuity at specified time points (e.g., 1 year after study
      presentation) is appropriate. Small case series should not be overinterpreted
      because of the effects of chance, and appropriate statistical analyses should be
      employed. CONCLUSIONS: Clinical case series often suffer from several potential
      reporting flaws. Correction of these flaws would permit the proper interpretation
      of the data and allow for the ability to combine data from several case series to
      assemble more meaningful and reliable conclusions.

PMID- 15860298
TI  - The importance of the refractive aspects of cataract surgery.

PMID- 15860299
TI  - The challenges and surprises of studying the genetics of age-related macular
      degeneration.

PMID- 15860300
TI  - Pigmented-membrane formation on acrylic intraocular lenses after
      phacoemulsification.
AB  - PURPOSE: To report the formation of pigmented membranes on acrylic intraocular
      lenses (IOLs) after phacoemulsification and to determine the clinical
      characteristics of these pigmented membranes. DESIGN: Observational case series.
      METHODS: Four eyes of three patients were found to have pigmented membranes on
      their acrylic IOLs (Sensar AR40). Their medical records were reviewed. RESULTS:
      The pigmented membranes were observed at 4- to 9-month intervals after
      phacoemulsification. Their best-corrected Snellen visual acuity (BCVA) decreased
      by more than 2 lines, ranging from 20/63 to 20/40. After Nd:YAG laser treatment,
      BCVA improved 2 to 4 lines. At 5- to 12-week intervals after Nd:YAG laser
      treatment, recurrences of the pigmented membranes were observed with decreased
      BCVA. CONCLUSIONS: We have observed visually significant, recurrent, pigmented
      membrane formation in eyes implanted with Sensar AR40 acrylic IOLs. To the best
      of our knowledge, pigmented membranes on acrylic IOLs have not been described
      previously.

PMID- 15860301
TI  - Preliminary efficacy and safety of zero diopter lens implantation in highly
      myopic eyes.
AB  - PURPOSE: To report the preliminary efficacy and safety of zero diopter (D)
      intraocular lens implantation in highly myopic eyes. DESIGN: Retrospective
      surgical case series. METHODS: Three highly myopic eyes with axial lengths
      greater than 30 mm were implanted with zero D Alcon model MA60MA 3-piece acrylic
      posterior chamber lenses at the time of cataract surgery. RESULTS: Uncorrected
      visual acuity improved from counting fingers to 20/20- and 20/40- in two eyes.
      Best-corrected visual acuity improved from 20/80 and 20/60+ to 20/20- in the same
      eyes. A third eye was at counting fingers before and after surgery, because of a
      staphyloma. The range of preoperative, intended postoperative, and achieved
      postoperative spherical equivalent refractive errors was -15.1 to -25.0 diopters,
      -0.20 to -1.44 diopters, and +0.13 to +0.50 diopters respectively. CONCLUSIONS:
      All eyes experienced mild hyperopic refractive errors after surgery. No retinal
      detachments occurred during the follow-up interval.

PMID- 15860302
TI  - Fuchs heterochromic cyclitis and ocular toxocariasis.
AB  - PURPOSE: To report the association of Fuchs heterochromic cyclitis (FHC) and
      ocular toxocariasis in a young adult. DESIGN: Observational case report. METHODS:
      A 26-year-old patient was referred for the management of a unilateral
      intermediate uveitis associated with a lower peripheral subretinal fibrotic
      lesion near the pars plana. Diagnosis of FHC was clinically confirmed. Laboratory
      examination was performed to exclude an infectious condition. RESULTS: LISA assay
      detected significant levels of IgG directed against Toxocara canis. Toxoplasmic
      serology was negative, excluding this differential diagnosis. Other examinations,
      including complete blood cell count, urinalysis, serum angiotensin-converting
      enzyme, lysosyme, chest CT scan, and syphilis serology were noncontributive.
      CONCLUSIONS: Previous studies have reported on the association of FHC and other
      parasitic conditions, such as toxoplasmosis but also on herpetic ocular
      infections. Serologic analysis for toxocariasis may be proposed in patients with
      FHC and retinal scars in the absence of toxoplasmosis.

PMID- 15860303
TI  - Recurrent retinal angiomatous proliferation after surgical ablation.
AB  - PURPOSE: To report a case of retinal angiomatous proliferation (RAP) treated by
      ablation of the feeding and draining vessels that recurred by 6 months
      postoperatively. DESIGN: Interventional case report. METHODS: Images from
      fluorescein angiography, indocyanine green (ICG) angiography, and optical
      coherence tomography (OCT) were examined before and after ablation. RESULTS: The
      hot spot on late-phase ICG, the leakage on fluorescein angiography, the pigment
      epithelial detachment, and macular edema on OCT decreased postoperatively.
      However, a large hyperfluorescent lesion was detected on ICG 6 months
      postoperatively with recurrent cystoid macular edema. CONCLUSIONS: A new RAP
      lesion can develop even after the original lesion seemed to resolve after
      ablation.

PMID- 15860304
TI  - Sixth and tenth nerve palsy secondary to pseudomonas infection of the skull base.
AB  - PURPOSE: To describe skull base osteomyelitis, an uncommon complication of
      chronic otitis media in the post-antibiotic era, as a cause for diplopia. DESIGN:
      Case report. METHODS: The records of a patient with skull base osteomyelitis were
      reviewed. RESULTS: A patient presented with a sixth nerve palsy and tenth nerve
      palsy. Magnetic resonance imaging, bone scan, and gallium scan were helpful in
      establishing the diagnosis. Cultures grew Pseudomonas. The treatment required
      long-term intravenous antibiotics. CONCLUSIONS: Pseudomonas skull-based
      osteomyelitis can produce a sixth nerve palsy as a result of the involvement of
      the clivus. Although uncommon in the post-antibiotic era, early recognition,
      appropriate diagnostic testing, and aggressive systemic antibiotic treatment
      might prevent permanent neurologic sequel.

PMID- 15860305
TI  - Corneal tattooing for the treatment of debilitating glare in a child with
      traumatic iris loss.
AB  - PURPOSE: To report the cosmetic and therapeutic use of corneal tattooing for a
      child with sectoral traumatic corneal scarring and symptomatic glare from
      sectoral traumatic iris loss. DESIGN: Interventional case report. METHODS: A six
      year-old girl underwent corneal tattooing (platinum chloride reduced by
      hydrazine) in the relevant scarred corneal sector. RESULTS: Six months after the
      procedure, the child enjoyed a more normal corneal appearance and no longer
      suffered from glare. Postoperative epithelial healing, however, was slow and
      required vigilance. CONCLUSIONS: Corneal tattooing can allow both cosmetic and
      therapeutic benefit when indicated in a child. However, postoperative healing may
      require management when using platinum chloride reduced by hydrazine.

PMID- 15860306
TI  - Corneal pseudomembrane from acute inflammatory response and fibrin formation to
      acute myeloid leukemic infiltrate.
AB  - PURPOSE: To describe an unusual ocular manifestation of a patient with acute
      myeloid leukemia (AML). DESIGN: Observational case report. METHODS: A 59-year-old
      woman with a history of preleukemic myelodysplastic syndrome (MDS) and status
      post bone marrow transplant (BMT) complained of a sudden onset of poor vision
      associated with a corneal pseudomembrane. Ocular graft vs host disease was
      suspected, and the pseudomembrane was excised for histopathologic examination.
      RESULTS: The pseudomembrane showed myeloblasts admixed with an acute inflammatory
      response suggestive of the development of AML, a complication of MDS. Bone marrow
      examination confirmed the diagnosis of relapsing AML. CONCLUSIONS: Acute myeloid
      leukemia could present as a pseudomembrane; thus, examination of relevant ocular
      tissue is recommended.

PMID- 15860307
TI  - Anatomical and functional characteristics in atrophic maculopathy associated with
      spinocerebellar ataxia type 7.
AB  - PURPOSE: To assess the anatomic and functional characteristics in a Korean family
      with spinocerebellar ataxia type 7-associated atrophic maculopathy. DESIGN:
      Observational case report. METHODS: Three patients in a family underwent
      funduscopic examination, fluorescein angiogram, full-field electroretinogram
      (ERG), electro-oculogram, and optical coherence tomography (OCT). Macular
      functions were assessed using multifocal ERG and scanning laser ophthalmoscope
      (SLO) microperimetry. RESULTS: Both eyes showed bull's eye configuration and cone
      rod dystrophy phenotype. OCT revealed that retinal thinning extended outside the
      visibly atrophic lesions. Multifocal ERG demonstrated that amplitudes from the
      six ring segments were reduced in a centrifugal pattern. SLO microperimetry
      showed that fixations were unstable and shifted superior to the atrophic lesions.
      The areas of functional deficits were greater than those of anatomic deficits.
      CONCLUSIONS: Macular functions were severely depressed in atrophic maculopathy
      associated with spinocerebellar ataxia type 7 in both the visibly atrophic areas
      and the areas without visible atrophy in a centrifugal pattern.

PMID- 15860308
TI  - Central retinal vein occlusion with further reduction of retinal blood flow one
      year after radial optic neurotomy.
AB  - PURPOSE: To report a case of central retinal vein occlusion (CRVO) that had
      vitrectomy with radial optic neurotomy (RON), but the retinal blood flow (RBF)
      was still reduced 1 year later. DESIGN: Interventional case report. METHODS: An
      80-year-old woman had undergone vitrectomy and RON for a CRVO. She had a complete
      ophthalmic examination, including the RBF analysis using the dye dilution method
      before and after RON. RESULTS: Seven months after RON, her visual acuity improved
      from 20/50 to 20/25, and her foveal thickness was decreased from 733 to 213
      microm. Indocyanine green angiography demonstrated chorioretinal anastomoses. At
      1 year postoperatively, the RBF was reduced from 23.2 to 18 0.1 pixel(2)/s, and
      the foveal thickness was increased to 767 microm. Her visual acuity decreased to
      20/100. The chorioretinal anastomoses were still patent. CONCLUSIONS: These
      results demonstrate that a further reduction of RBF can occur after RON, and
      blood flow in the chorioretinal anastomoses may be insufficient to prevent the
      event.

PMID- 15860309
TI  - Use of surodex in phacotrabeculectomy surgery.
AB  - PURPOSE: To evaluate the use of Surodex (Oculex Pharmaceuticals, Sunnyvale,
      California) a drug delivery system incorporating 60 micrograms of dexamethasone
      in a pellet, in phacotrabeculectomy surgery. DESIGN: Nonrandomized, prospective,
      interventional case series. METHODS: Phacotrabeculectomy was performed on 37
      Asian subjects with primary open-angle glaucoma (POAG) using a standardized
      technique. All subjects received a Surodex pellet underneath the scleral flap.
      Results were compared with those of 31 POAG subjects who had undergone
      phacotrabeculectomy augmented with 50 mg/ml of intraoperative 5-fluorouracil (5
      FU) during the same period. RESULTS: Mean follow-up in months was 19.7 +/- 7.9
      and 22.1 +/- 6.2 for the Surodex and 5-FU groups, respectively (P = .29). There
      was a 20.1% decrease in intraocular pressure in the Surodex group compared with
      28.5% decrease in the 5-FU group (P = .6). Postoperative complications occurred
      in three cases (8.1%) and six cases (19.3%), respectively (P = .04). CONCLUSIONS:
      Combined phacotrabeculectomy surgery augmented by intra-scleral placement of
      Surodex results in good control of IOP and a low incidence of complications.

PMID- 15860310
TI  - Extensive upper-extremity venous thrombosis after fluorescein angiography.
AB  - PURPOSE: To report a case of extensive cephalic and basilic venous thrombosis
      after fluorescein angiography. DESIGN: Interventional case report. METHODS: A 38
      year-old Chinese male presented with blurring of vision in his left eye. Clinical
      examination revealed central serous retinopathy, and a routine fluorescein
      angiography was performed. RESULTS: He developed inflammation over the right arm
      over 4 days. Duplex scan disclosed extensive superficial venous thrombosis of the
      right upper limb with occlusion of the basilic vein and cephalic vein in the
      proximal right upper arm to the level of the midarm. He was treated medically but
      was subsequently lost to follow-up. CONCLUSIONS: Extensive upper-extremity venous
      thrombosis is infrequent after single-shot intravenous cannulation. Venous
      thrombosis occurring after fluorescein angiography has not been reported up to
      this time. It is possible that proper arm positioning during the procedure may
      reduce this risk, and ophthalmologists should be vigilant of this potentially
      unusual complication.

PMID- 15860311
TI  - Staphylococcus hominis endophthalmitis associated with a capsular hypopyon.
AB  - PURPOSE: To report a case of Staphylococcus hominis endophthalmitis associated
      with a capsular hypopyon. DESIGN: Interventional case report. METHODS: A 51-year
      old man presented with chronic postcataract extraction inflammation and underwent
      vitrectomy, partial capsulectomy, and intravitreal antibiotic injections,
      followed by explantation of the intraocular lens and capsule. RESULTS: A capsular
      hypopyon in the absence of an anterior chamber hypopyon was noted. Cultures of
      the vitreous and capsule revealed Staphylococcus hominis, a coagulase-negative
      gram-positive organism. CONCLUSIONS: We are unaware of previous reports of
      endophthalmitis caused by Staphylococcus hominis, and could find none in a
      computerized search using MEDLINE. This case adds Staphylococcus hominis to the
      list of causative organisms in chronic endophthalmitis and illustrates the rare
      finding of a capsular hypopyon.

PMID- 15860312
TI  - Lash ptosis caused by latanoprost.
AB  - PURPOSE: To report a case of lash ptosis caused by latanoprost. DESIGN:
      Observational case report. METHODS: Retrospective chart review. RESULTS: A 61
      year-old, ocular hypertensive man who was using latanoprost OU presented with
      trichomegaly and bilateral lash ptosis. The lash ptosis had not resolved 6 months
      after stopping latanoprost, and anterior lamellar repositions were performed. At
      last follow-up, 8 months after surgery, the lids were in a normal position, but
      the trichomegaly had reduced only slightly. CONCLUSIONS: Lash ptosis should be
      considered as a possible complication of latanoprost therapy.

PMID- 15860313
TI  - Cancer-associated nummular loss of the pigment epithelium.
AB  - PURPOSE: To report a case of bilateral diffuse uveal melanocytic proliferation
      (BDUMP) that had areas of retinal pigment epithelial loss. DESIGN: Observational
      case report. METHODS: A 67-year-old woman with a history of uterine cancer
      presented with 4 months of bilateral visual loss. RESULTS: Although B-scan
      ultrasonography revealed both small shallow serous retinal and choroidal
      detachments in the periphery, the choroid was normal in thickness. Fluorescein
      angiography revealed numerous nummular-shaped areas of transmission defects
      suggesting retinal pigment epithelium loss. Autofluorescence photography showed
      complete absence of autofluorescence in these nummular areas, and optical
      coherence tomography showed segmental areas with lack of any signal from affected
      areas of the retinal pigment epithelium, suggesting complete loss of retinal
      pigment epithelium cells. CONCLUSIONS: Although the fundus findings in BDUMP have
      been attributed to the proliferation of uveal melanocytic cells in the outer
      choroid in previous papers, our patient had nummular areas of loss of the retinal
      pigment epithelium as the apparent reason for visual decline.

PMID- 15860314
TI  - Atypical presentation of multiple evanescent white dot syndrome involving
      granular lesions of varying size.
AB  - PURPOSE: To report an atypical presentation of multiple evanescent white dot
      syndrome (MEWDS). DESIGN: Observational case report. METHODS: Review of the
      clinical, laboratory, photographic, and angiographic records of a patient with
      MEWDS. RESULTS: A 29-year-old woman presented with 20/400 vision in the right eye
      associated with multiple, granular lesions of varying sizes (100-1000 microm) in
      the outer retina, a prominent panuveitis, diffuse choroidal thickening and
      enlarged blindspot. The multiple lesions and visual disturbances resolved within
      4 weeks with corticosteroid treatment, and the patient was diagnosed with MEWDS.
      CONCLUSIONS: Clinicians should be aware of atypical manifestations of MEWDS. The
      patient's unusual fundoscopic changes and prominent intraocular inflammatory
      reaction are findings that have not been reported in patients with MEWDS.

PMID- 15860315
TI  - Terror-related open-globe injuries: a 10-year review.
AB  - PURPOSE: To describe mechanisms and injury characteristics influencing visual
      outcomes in eyes with open-globe injuries sustained in terrorist acts. DESIGN:
      Retrospective, interventional case series. METHODS: The charts of 260 consecutive
      patients (285 eyes) who had open-globe injury caused by terrorist attack and
      admitted to the tertiary referral center for military in Turkey between March
      1991 and April 2001 were reviewed, and 50 patients (56 eyes) with complete data
      were evaluated for predicting visual outcome according to the Ocular Trauma
      Classification System (OTCS). RESULTS: The mean age of patients was 22.6 years,
      and the mean follow-up was 5.8 months. Seventeen patients (6.54%) had traumatic
      amputation in the extremities. Forty-eight eyes (16.84%) were enucleated. Type A,
      grade V, zone III, and RAPD-positive injuries were associated with unfavorable
      visual outcome. Land mine and hand grenade injuries had the worst outcome.
      CONCLUSIONS: In terror-related open-globe injuries, unusual presentations and
      devastating visual results are common, and OTCS seems to predict visual outcomes.

PMID- 15860316
TI  - Ethanolamine oleate sclerotherapy in the management of orbito-palpebral cyst
      associated with congenital microphthalmos.
AB  - PURPOSE: To report a novel, nonsurgical method of management of orbito-palpebral
      cyst associated with congenital microphthalmos. DESIGN: Interventional case
      series. METHODS: Two patients with orbito-palpebral cyst were included. Case 1
      had bilateral orbito-palpebral cyst, whereas case 2 was unilateral.
      Transcutaneous cyst aspiration in both cases revealed a severely microphthalmic
      eye with no visual potential. Ethanolamine oleate sclerotherapy was performed
      immediately after cyst aspiration in both patients. RESULTS: Complete resolution
      of the orbito-palpebral cysts was noted within 6 weeks, and the custom prosthesis
      was well retained. CONCLUSIONS: Ethanolamine oleate sclerotherapy may be an
      effective minimal intervention treatment option for cosmetic rehabilitation of
      patients with orbito-palpebral cyst associated with congenital microphthalmos
      with no visual potential.

PMID- 15860317
TI  - Inverse mushroom-shaped nonmechanical penetrating keratoplasty using a
      femtosecond laser.
AB  - PURPOSE: To demonstrate the feasibility of an inverse mushroom-shaped
      nonmechanical corneal trephination using a femtosecond laser in a noncontact
      manner. DESIGN: Experimental study. METHODS: In this laboratory study, 10
      polymethylmethacrylate (PMMA) blocks and 20 porcine corneas were treated with an
      industrial femtosecond laser source. The trephination profile consisted of (1) a
      7- or 6-mm diameter cylinder from the anterior chamber, (2) an intermediate
      horizontal connecting plane, and (3) a concentric 5- or 4-mm diameter cylinder
      upwards. RESULTS: Applying appropriate combinations of pulse energy and spacing,
      trephination took less than 60 seconds. In porcine eyes, light microscopy
      displayed trephination edges delineated by partly confluent gas bubbles (10-40
      mum) with tissue bridges in between. By TEM, the cut edges were lined by a
      delicate, electron-dense layer (5-40 nm). CONCLUSIONS: Femtosecond laser
      technology seems to offer a promising approach towards minimally invasive self
      sealing "no-stitch keratoplasty."

PMID- 15860318
TI  - Normal retinal vasculature despite familial protein C deficiency.
AB  - PURPOSE: It is unclear whether protein C deficiency is associated with retinal
      venous occlusive disease. DESIGN: We performed a cross-sectional study. METHODS:
      Members of a protein C-deficient family, either deficient or nondeficient, with a
      history of nonocular venous thrombosis were included. All participants completed
      questionnaires regarding their medical and ophthalmic histories. Each subject
      underwent dilated direct ophthalmoscopic and binocular indirect ophthalmoscopic
      examinations by a single vitreoretinal specialist. RESULTS: None of the 18 family
      members with a known history of nonocular thrombosis-12 with and 6 without
      protein C deficiency- manifested stigmas of recent or chronic retinal vascular
      occlusive disease. CONCLUSIONS: This study showed no evidence of involvement of
      the retinal vascular bed in a family with an increased risk of nonocular venous
      thrombosis attributable to the deficiency of protein C.

PMID- 15860319
TI  - Optical coherence tomography in presumed congenital simple hamartoma of retinal
      pigment epithelium.
AB  - PURPOSE: To report the optical coherence tomography (OCT) findings in two cases
      of presumed congenital simple retinal pigment epithelial (RPE) hamartoma. DESIGN:
      Observational case report. METHODS: Fundus examination, fluorescein angiography,
      ultrasonography, and OCT were done on two cases of simple RPE hamartoma. RESULTS:
      A heavily pigmented solitary macular lesion was noted in the right eye of a 22
      year-old man and a 55-year-old woman. The young man had a foveal lesion and a
      vision of 10/200; the woman with eccentric lesion had a vision of 20/20. The
      lesions blocked fluorescence on angiogram; sonography showed hyper-reflective
      nodules. OCT demonstrated full-thickness retinal replacement, complete optical
      shadowing, and abrupt margins of the lesion in both the cases, and vitreomacular
      adhesion at the temporal margin of the foveal lesion. CONCLUSIONS: Congenital
      simple RPE hamartoma may rarely occur at the foveal center, resulting in poor
      visual acuity. OCT is a useful non-invasive adjunct for diagnosis of this rare
      tumor and may reveal additional features like vitreoretinal adhesion.

PMID- 15860321
TI  - Attrition from ophthalmology residency programs.

PMID- 15860323
TI  - Intrasurgical plasmin enzyme in diabetic macular edema.

PMID- 15860325
TI  - Ocular side effects from herbal medicines and nutritional supplements.

PMID- 15860326
TI  - Risks of computerized tomography in the evaluation of chronic uveitis.

PMID- 15860328
TI  - Cystoid macular edema from niacin typically is not accompanied by fluorescein
      leakage on angiography.

PMID- 15860329
TI  - In-the-bag intraocular lens dislocation.

PMID- 15860333
TI  - More about self-sealing pars plana stitch incisions.

PMID- 15860334
TI  - Families at high and low risk for depression: a three-generation startle study.
AB  - BACKGROUND: Anxiety symptoms might be a vulnerability factor for the development
      of major depressive disorder (MDD). Because elevated startle magnitude in
      threatening contexts is a marker for anxiety disorder, the present study
      investigated the hypothesis that enhanced startle reactivity would also be found
      in children and grandchildren of individuals with MDD. METHODS: The magnitude of
      startle was investigated in two tests (anticipation of an unpleasant blast of air
      and during darkness) in children (second generation) and grandchildren (third
      generation) of probands with (high risk) or without (low risk) MDD (first
      generation). RESULTS: Startle discriminated between the low- and high-risk
      groups. In the probands' children, the high-risk group showed increased startle
      magnitude throughout the fear-potentiated startle test. In the probands'
      grandchildren, a gender-specific abnormality was found in the high-risk group
      with high-risk girls, but not boys, exhibiting elevated startle magnitude
      throughout the procedure. CONCLUSIONS: Increased startle reactivity in
      threatening contexts, previously found in patients with anxiety disorder and in
      children of parents with an anxiety disorder, might also constitute a
      vulnerability marker for MDD. These findings suggest that there might be common
      biologic diatheses underlying depression and anxiety.

PMID- 15860335
TI  - Selective reduction in amygdala volume in pediatric anxiety disorders: a voxel
      based morphometry investigation.
AB  - BACKGROUND: Significant controversy has emerged concerning pediatric anxiety
      disorders. Some researchers question the justification for diagnosing and
      treating pediatric anxiety disorders, owing to concerns about the inappropriate
      medicalization of social problems. Others note the importance of diagnosis and
      treatment, given that pediatric anxiety disorders represent a strong risk factor
      for serious adult mental disorders. We examine the neural correlates of pediatric
      anxiety disorders, to consider the validity of the categorization scheme used in
      recent treatment studies. METHODS: Using inclusion criteria derived from recent
      treatment trials, we compared gray matter volume throughout the brain in children
      with and without anxiety. Morphometric analyses used optimized voxel-based
      morphometry, an automated method for examining structural changes throughout the
      brain. RESULTS: Reductions in left amygdala gray matter volume were noted for
      patients with anxiety disorders relative to comparison subjects. CONCLUSIONS: We
      discuss implications of these findings for current controversies.

PMID- 15860337
TI  - Increased activation of the anterior cingulate cortex during processing of
      disgust faces in individuals with social phobia.
AB  - BACKGROUND: Researchers have examined the role of differential activation of
      various brain regions involved in processing emotional information in subjects
      with social phobia. These studies have focused mostly on the activation of the
      amygdala. The anterior cingulate cortex (ACC) also has been implicated in
      processing emotional information, but its role in social phobia has not been
      examined. METHODS: We recruited subjects with social phobia and matched them with
      non-anxious control subjects. Participants viewed facial expressions of disgust
      ("disgust faces") and neutral facial expressions ("neutral faces"). We measured
      brain activation, focusing on the ACC, using functional magnetic resonance
      imaging. We also recorded participants' ratings of emotional valence of faces, as
      well as response latencies to make these valence judgments. We repeated this
      procedure using three different sets of facial expressions. RESULTS: Individuals
      with social phobia exhibited a significant increase in ACC activity compared with
      non-anxious control subjects when processing disgust versus neutral faces.
      Additionally, compared with control subjects, subjects with social phobia were
      faster in their ratings of disgust faces and rated the neutral faces more
      negatively. CONCLUSIONS: Our findings demonstrate that the ACC might be involved
      in affective processing of negative information in socially phobic subjects.

PMID- 15860336
TI  - Enlarged striatum in abstinent methamphetamine abusers: a possible compensatory
      response.
AB  - BACKGROUND: Little is known about structural brain abnormalities associated with
      methamphetamine (METH) abuse; therefore, we aimed: 1) to evaluate possible
      morphometric changes, especially in the striatum of recently abstinent METH
      dependent subjects; 2) to evaluate whether morphometric changes are related to
      cognitive performance; and 3) to determine whether there are sex-by-METH
      interactions on morphometry. METHODS: Structural MRI was performed in 50 METH and
      50 comparison subjects with the same age range and sex proportion; quantitative
      morphometric analyses were performed in the subcortical gray matter, cerebellum
      and corpus callosum. Neuropsychological tests were also performed in 44 METH and
      28 comparison subjects. RESULTS: METH users showed enlarged putamen (left: +
      10.3%, p = .0007; right: + 9.6%, p = .001) and globus pallidus (left: + 9.3%, p =
      .002; right: + 6.6%, p = .01). Female METH subjects additionally showed larger
      mid-posterior corpus callosum (+ 9.7%, p = .05). Although METH users had normal
      cognitive function, those with smaller striatal structures had poorer cognitive
      performance and greater cumulative METH usage. CONCLUSIONS: Since METH subjects
      with larger striatal structures had relatively normal cognitive performance and
      lesser cumulative METH usage, the enlarged putamen and globus pallidus might
      represent a compensatory response to maintain function. Possible mechanisms for
      the striatal enlargement include glial activation and inflammatory changes
      associated with METH-induced injury.

PMID- 15860338
TI  - Reduced activation of posterior cingulate cortex during imagery in subjects with
      high degrees of alexithymia: a functional magnetic resonance imaging study.
AB  - BACKGROUND: Although the brain areas involved in imagery have been reported, the
      neural bases of individual differences in imagery remain to be elucidated. People
      with high degrees of alexithymia (HDA) are known to have constricted imaginal
      capacities. The purpose of this study was to investigate neural correlates of
      imagery disturbance in subjects with HDA. METHODS: A functional magnetic
      resonance imaging (fMRI) study was undertaken in 10 subjects with HDA and 10
      subjects with low degrees of alexithymia (LDA), who were selected according to
      their scores on the 20-item Toronto Alexithymia Scale (TAS-20). The two groups'
      regional cerebral activation was compared during various imagery conditions. In
      those conditions, the subjects imaged a past happy (PH) event, a past sad (PS)
      event, a past neutral (PN) event, a future happy (FH) event, a future sad (FS)
      event, and a future neutral (FN) event. The activation levels during these
      conditions were compared with those during a rest condition (REST). RESULTS: The
      t tests showed that the mean subjective ratings of both the vividness of the
      imagery and the intensity of emotion during the imagery were higher in the
      subjects with LDA than in those with HDA for the PS and FS imagery conditions. On
      the other hand, relative to the LDA group, the HDA group showed significantly
      less activation in the posterior cingulate cortex (PCC) during the PH and FH
      imagery conditions compared with REST and during the FH imagery condition
      compared with the FN imagery condition. CONCLUSION: The present results suggest
      an association between an HDA and reduced activation of the PCC during happy
      imagery. Given the function of this brain region, these results might be related
      to a dysfunction of episodic memory retrieval during happy imagery in subjects
      with HDA.

PMID- 15860339
TI  - Functional disconnectivity of the medial temporal lobe in Asperger's syndrome.
AB  - BACKGROUND: Autistic spectrum disorders (ASD) are neurodevelopmental conditions
      that may be caused by abnormal connectivity between brain regions constituting
      neurocognitive networks for specific aspects of social cognition. METHODS: We
      used three-way multidimensional scaling of regionally parcellated functional
      magnetic resonance imaging (fMRI) data to explore the hypothesis of abnormal
      functional connectivity in people with ASD. Thirteen high-functioning individuals
      with Asperger's syndrome and 13 healthy volunteers were scanned during incidental
      processing of fearful facial expressions. RESULTS: Using permutation tests for
      inference, we found evidence for significant abnormality of functional
      integration of amygdala and parahippocampal gyrus (p < .05, false discovery rate
      [FDR] corrected) in people with Asperger's syndrome. There were less salient
      abnormalities in functional connectivity of anterior cingulate, inferior
      occipital, and inferior frontal cortex, but there was no significant difference
      between groups in whole brain functional connectivity. CONCLUSIONS: We conclude
      there is evidence that functional connectivity of medial temporal lobe structures
      specifically is abnormal in people with Asperger's syndrome during fearful face
      processing.

PMID- 15860340
TI  - The dopamine D4 receptor gene 48-base-pair-repeat polymorphism and mood
      disorders: a meta-analysis.
AB  - BACKGROUND: We conducted a meta-analysis to re-evaluate the role of the dopamine
      D4 receptor gene 48-base-pair- repeat (DRD4) polymorphism in mood disorders.
      METHODS: DRD4 allele frequencies were compared between 917 patients with unipolar
      (UP) or bipolar affective disorder (BP) and 1164 control subjects from 12
      samples, using the Cochrane Review Manager. RESULTS: An association was found
      between all mood disorder groups and DRD4.2. After correcting for multiple
      testing, the association between DRD4.2 and BP dropped to insignificance;
      however, the evidence of an association between the DRD4.2 allele and UP (p <
      .001) and the combined group (p < .001) remained. There was no evidence for
      heterogeneity or publication bias. CONCLUSIONS: These findings suggest that the
      DRD4.2 allele is a risk allele for depression symptomatology. Meta-analysis may
      be a valuable objective tool for a quantitative summary of evidence for
      association studies in psychiatric genetics.

PMID- 15860341
TI  - Electroconvulsive shock decreases binding to 5-HT2 receptors in nonhuman
      primates: an in vivo positron emission tomography study with [18F]setoperone.
AB  - BACKGROUND: Dysfunction within the serotonin (5-HT) system plays a major role in
      the etiology of human depression, and treatment with antidepressant drugs
      downregulates 5-HT(2) receptors in rodents and humans. The consequences of
      another effective antidepressant treatment, electroconvulsive therapy (ECT), on 5
      HT(2) receptors are less established. METHODS: We studied the effects of a course
      of electroconvulsive shock (ECS) on 5-HT(2) receptor binding in nonhuman primates
      in vivo using positron emission tomography (PET) and the radiotracer
      [(18)F]setoperone. Seven adult male rhesus monkeys received two bilateral ECS
      treatments per week for 3 weeks; PET scans were performed before treatment, and
      24 hours, 1 week, and 4-6 weeks after completion of the course of ECS. Regions of
      interest were placed throughout the cortex, and the data analyzed as the ratio of
      specific:nonspecific radioactivity accumulation, with the cerebellum used as a
      measure of nonspecific binding. RESULTS: Serotonin 5-HT(2) binding was
      significantly decreased at 24 hours and 1 week post-ECS, but returned to baseline
      4-6 weeks posttreatment. CONCLUSIONS: These results show for the first time in a
      primate species that chronic ECS decreases binding to 5-HT(2) receptors and
      indicate that 5-HT(2) receptor downregulation may be a common effect of both
      pharmacologic and nonpharmacologic antidepressant treatments.

PMID- 15860342
TI  - Sustained activation of the hippocampus in response to fearful faces in
      schizophrenia.
AB  - BACKGROUND: In healthy individuals, the activity of the medial temporal lobe
      habituates rapidly with the repeated presentation of a stimulus. Using functional
      magnetic resonance imaging (fMRI), we tested the hypothesis that habituation of
      the medial temporal lobe is reduced in schizophrenia. METHODS: During fMRI
      scanning, fearful and happy faces were presented repeatedly to healthy control
      subjects (n =16) and patients with schizophrenia (n =18). Habituation of medial
      temporal lobe structures was measured by comparing the hemodynamic response
      occurring during the early and late portions of the presentation of each face.
      RESULTS: Control subjects demonstrated significant medial temporal lobe
      habituation to fearful but not to happy faces. In contrast, patients with
      schizophrenia did not demonstrate medial temporal lobe habituation in response to
      fearful or happy faces. In a direct, between-group comparison, right hippocampal
      habituation to fearful faces was significantly greater in control subjects than
      in the schizophrenia patients. Also, there were no significant differences
      between the patients and control subjects in the early medial temporal lobe
      response to fearful faces, suggesting that attenuated hippocampal habituation in
      schizophrenia is not associated with a reduction in initial activation.
      CONCLUSIONS: These findings suggest that there is abnormal modulation of
      hippocampal responses to fearful faces in schizophrenia.

PMID- 15860343
TI  - Atypical hemispheric specialization for language in right-handed schizophrenia
      patients.
AB  - BACKGROUND: The literature suggests that schizophrenia could be related to a
      failure in the setting up of left hemisphere dominance for language. We sought to
      determine hemispheric specialization for language in schizophrenic patients,
      using functional magnetic resonance imaging. METHODS: Twenty-one right-handed
      patients with DSM-IV schizophrenia and 21 right-handed control subjects matched
      by age, gender, and level of education were recruited. Fractional blood oxygen
      level dependent (BOLD) signal variations in anatomic regions of interest were
      compared between groups. Functional asymmetry indices (FAIs) were calculated in a
      region (LANG) resulting from the merging of activated regions showing a Group x
      Hemisphere interaction. The FAI difference between each patient and their matched
      control subject was computed. RESULTS: We found lower BOLD signal changes in
      patients as compared with their control subjects in a network comprising areas of
      the left middle temporal gyrus, the left angular gyrus, and the pars triangularis
      of the left inferior frontal gyrus, merged to constitute LANG. The intra-pair
      differences of FAIs in this area showed that 76% of the patients exhibited less
      leftward functional asymmetry than their matched control subjects, including six
      patients with a rightward asymmetry. CONCLUSIONS: These results demonstrated the
      existence of an anomaly in left hemisphere specialization for language in
      schizophrenic subjects.

PMID- 15860344
TI  - Abnormal hemodynamics in schizophrenia during an auditory oddball task.
AB  - BACKGROUND: Schizophrenia is a heterogeneous disorder characterized by diffuse
      brain abnormalities that affect many facets of cognitive function. One replicated
      finding in schizophrenia is abnormalities in the neural systems associated with
      processing salient stimuli in the context of oddball tasks. This deficit in the
      processing of salience stimuli might be related to abnormalities in orienting,
      attention, and memory processes. METHODS: Behavioral responses and functional
      magnetic resonance imaging data were collected while 18 patients with
      schizophrenia and 18 matched healthy control subjects performed a three-stimulus
      auditory oddball task. RESULTS: Target detection by healthy participants was
      associated with significant activation in all 38 regions of interest embracing
      distributed cortical and subcortical systems. Similar reproducibility was
      observed in healthy participants for processing novel stimuli. Schizophrenia
      patients, relative to control subjects, showed diffuse cortical and subcortical
      hypofunctioning during target detection and novelty processing, including
      bilateral frontal, temporal, and parietal cortices and amygdala, thalamus, and
      cerebellum. CONCLUSIONS: These data replicate and extend imaging studies of
      target detection in schizophrenia and present new insights regarding novelty
      processing in the disorder. The results are consistent with the hypothesis that
      schizophrenia is characterized by a widespread pathologic process affecting many
      cerebral areas, including cortical, subcortical, and cerebellar circuits.

PMID- 15860346
TI  - Inhibitory control of saccadic eye movements and cognitive impairment in
      Alzheimer's disease.
AB  - BACKGROUND: This study examined the relationship of inhibitory control and
      measures of neuropsychological impairment in patients with early Alzheimer's
      disease (AD). Four specific questions were addressed: 1) Which error parameters
      of saccadic inhibition are sensitive to AD? 2) Which inhibitory deficits are
      related to cognitive measures of impairment? 3) Is the inhibitory impairment in
      AD dependent on the initiation of a volitional eye movement? 4) How do the
      effects of saccadic inhibitory control in AD relate to the normal effects of
      aging? METHODS: Eighteen patients with probable AD and two control groups
      (seventeen young, and eighteen old participants) completed a battery of
      neuropsychological tests and four saccadic eye movement paradigms: pro-saccade,
      NO-GO, GO/NO-GO and anti-saccade. RESULTS: Old controls generated increased
      inhibition errors in comparison to young controls in the GO/NO-GO paradigm. In
      comparison to old controls, AD generated normal saccades in the pro-saccade
      paradigm, but showed a higher proportion of inhibition errors in the NO-GO, GO/NO
      GO and anti-paradigms. The frequency of uncorrected errors in the anti-saccade
      paradigm was positively correlated with cognitive measures of dementia.
      CONCLUSIONS: AD patients have an impairment of inhibitory control and error
      correction that exceeds the effects of normal aging and is related to the
      severity of dementia. However, the inhibitory impairment is not contingent on the
      interaction with a volitional saccade.

PMID- 15860345
TI  - Antipsychotic drugs elevate mRNA levels of presynaptic proteins in the frontal
      cortex of the rat.
AB  - BACKGROUND: Molecular adaptations are believed to contribute to the mechanism of
      action of antipsychotic drugs (APDs). We attempted to establish common gene
      regulation patterns induced by chronic treatment with APDs. METHODS: Gene
      expression analysis was performed with the Affymetrix U34A array in the frontal
      cortex (FC) and the striatum of rats chronically treated with two concentrations
      of either clozapine or haloperidol. Key data were verified with real-time
      quantitative polymerase chain reaction. RESULTS: Many genes in the FC affected by
      APD-treatment contribute to similar functions. mRNAs coding for synaptic vesicle
      docking- and microtubule-associated proteins were upregulated; mRNAs for serine
      threonine protein phosphatases were downregulated, whereas the serine-threonine
      kinases protein kinase A, protein kinase C, and calcium/calmodulin kinase II
      alpha and IV were upregulated, indicating increased potential for protein
      phosphorylation. In the striatum, altered gene expression was less focused on
      genes of particular function or location, and the high concentration of
      haloperidol had a different gene expression profile than any of the other APD
      treatments. CONCLUSION: We found an increase in the transcription of genes coding
      for proteins involved in synaptic plasticity and synaptic activity in the FC. We
      furthermore found that the gene expression profile of APDs is different between
      FC and striatum.

PMID- 15860347
TI  - Permanent deficits in serotonergic functioning of olfactory bulbectomized rats:
      an in vivo microdialysis study.
AB  - BACKGROUND: Bilateral removal of the olfactory bulbs (OBX) in rats results in a
      complex constellation of behavioral, neurochemical, neuroendocrine, and
      neuroimmune alterations, many of which are also reported in patients with major
      depressive disorder (MDD). Drawing on clinical findings, there has been
      considerable interest in the role of serotonin in the mechanism of action of OBX.
      However, to date, there has been no report of direct measurement of serotonergic
      functioning of bulbectomized animals using microdialysis. The present study
      describes the effects of olfactory bulbectomy on functioning of the serotonergic
      system. METHODS: In vivo microdialysis was performed in conscious rats that
      underwent OBX or sham surgery. Alterations in the functioning of the serotonergic
      system were assessed by administration of fluvoxamine, fenfluramine, and 3
      hydroxybenzylhydrazine (NSD-1015). Animals were also repeatedly tested in an open
      field. RESULTS: Bilateral removal of the olfactory bulbs decreased basal
      extracellular levels by decreasing the releasable pool of serotonin (5-HT) in the
      basolateral amygdala 2 weeks after surgery and in the dorsal hippocampus 2 weeks
      and 5 months after surgery. Olfactory bulbectomized animals showed a lower rate
      of 5-HT synthesis under basal conditions. However, the capacity of the system to
      synthesize 5-HT was not affected. Olfactory bulbectomized rats were hyperactive
      in the open field. This hyperactivity remained after successive testing,
      indicating permanent behavioral changes. CONCLUSIONS: This microdialysis study
      shows that OBX has profound and long-lasting effects on serotonergic functioning
      and on activity levels and is therefore considered an intriguing and promising
      animal model for affective processes in the brain.

PMID- 15860348
TI  - Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed
      patients probably results from lowered platelet BDNF release unrelated to
      platelet reactivity.
AB  - BACKGROUND: Recent reports have suggested a role for brain-derived neurotrophic
      factor (BDNF) in psychiatric disorders. Decreased serum BDNF levels have been
      reported in major depression, but the cause of this decrease has not yet been
      investigated. The goal of this study was to assess blood BDNF and a platelet
      activation index, PF4. METHODS: Forty-three drug-free patients (27 female, 16
      male) diagnosed with major depression and 35 healthy control subjects (18 female,
      17 male) were assessed for plasma, serum, and blood BDNF content. Brain-derived
      neurotrophic factor and PF4 were assayed with enzyme-linked immunosorbent assay
      methods, and severity of depression was evaluated with the Montgomery-Asberg
      Depression Rating Scale. RESULTS: Serum and plasma BDNF levels were decreased in
      depressed patients compared with control subjects. In whole blood, BDNF levels
      were unaltered in the depressed subjects compared with control subjects. The
      serum/blood BDNF ratio was lower in patients with major depression. Increased
      plasma but not serum PF4 levels were observed in depressed subjects compared with
      control subjects. CONCLUSIONS: Our results suggest that an alteration of serum or
      plasma BDNF is not due to the change in blood BDNF but rather is probably related
      to mechanisms of BDNF release. Secretion of BDNF seems to be independent of
      platelet reactivity; other mechanisms are therefore probably involved and need to
      be elucidated.

PMID- 15860349
TI  - Obsessive-compulsive symptoms among patients with Sydenham chorea.
AB  - BACKGROUND: Among patients with tic disorders, a distinctive clinical profile of
      obsessive-compulsive symptomatology has been described. The present investigation
      was designed to document the phenomenology of obsessive-compulsive symptoms (OCS)
      among patients with Sydenham chorea (SC), the neurologic variant of rheumatic
      fever. We hypothesized that OCS occurring in association with SC would be similar
      to those among patients with tic disorders. METHODS: The authors studied the
      presence of OCS in 73 patients with SC by using the Yale-Brown Obsessive
      Compulsive Scale at the Pediatric Clinics of the University of Sao Paulo Medical
      Center in Sao Paulo, Brazil (n = 45) and at the National Institute of Mental
      Health in Bethesda, Maryland (n = 28). RESULTS: The most frequent symptoms
      observed among subjects with comorbid SC and OCS were aggressive, contamination,
      and somatic obsessions and checking, cleaning, and repeating compulsions. A
      principal component factor analysis yielded a five-factor solution (accounting
      for 64.5% of the total variance), with contamination and symmetry obsessions and
      cleaning compulsions loading highly. CONCLUSIONS: The symptoms observed among the
      SC patients were different from those reported by patients with tic disorders but
      were similar to those previously noted among samples of pediatric patients with
      primary obsessive-compulsive disorder.

PMID- 15860350
TI  - A combination of molecular cytogenetic analyses reveals complex genetic
      alterations in conventional renal cell carcinoma.
AB  - Here we report the complex pattern of genomic imbalances and rearrangements in a
      panel of 19 renal cell carcinoma cell lines detected with molecular cytogenetic
      analysis. Consistent heterogeneity in chromosome number was found, and most cell
      lines showed a near-triploid chromosome complement. Several cell lines showed
      deletions of the TP53 (alias p53), CDKN2A (alias p16), and VHL genes. Multiplex
      fluorescence in situ hybridization (M-FISH) analysis revealed chromosome 3
      translocated to several other partners chromosomes, as well as breakage events
      commonly affecting chromosomes 1, 5, 8, 10, and 17. The most common abnormality
      detected with comparative genomic hybridization (CGH) was deletions of chromosome
      3p, with loss of the RASSF1, FHIT, and p44S10 loci frequently involved. CGH gain
      of 5q showed overrepresentation of the EGR1 and CSF1R genes. Recurrent
      alterations to chromosome 7 included rearrangement of 7q11 and gains of the EGFR,
      TIF1, and RFC2 genes. Several lines exhibited rearrangement of 12q11
      approximately q14 and overrepresentation of CDK4 and SAS loci. M-FISH revealed
      several other recurrent translocations, and CGH findings included loss of 9p,
      14q, and 18q and gain of 8q, 12, and 20. Further genomic microarray changes
      included loss of MTAP, IGH@, HTR1B, and SMAD4 (previously MADH4) and gains of MYC
      and TOP1. An excellent correlation was observed between the genomic array and
      FISH data, demonstrating that this technique is effective and accurate. The
      aberrations detected here may reflect important pathways in renal cancer
      pathogenesis.

PMID- 15860351
TI  - AURKA amplification, chromosome instability, and centrosome abnormality in human
      pancreatic carcinoma cells.
AB  - To test the hypothesis that AURKA amplification contributes to pancreatic
      tumorigenesis by increasing centrosome abnormality and chromosome instability,
      the current study explored the associations between AURKA amplification,
      chromosome instability, centrosome abnormality, and the expression of several
      important proteins that are involved in cell proliferation (Ki-67), cell cycle
      regulation (p53, p16), and apoptosis (survivin) in 12 human pancreatic carcinoma
      cell lines. Using fluorescence in situ hybridization (FISH), we observed that 5
      of the 12 cell lines had an AURKA amplification index (AI) (percentage of cells
      with more than three signals) >60%. Both the AURKA AI and the average number of
      signals per cell (ANSPC) were significantly associated with the copy number of
      chromosome 9 but not chromosome 17. The AURKA ANSPC was positively associated
      with the percentage of cells with the centrosome abnormality. Furthermore,
      centrosome abnormality was significantly associated with the frequency of cells
      with abnormal nuclei and abnormal mitotic figures, but no direct association was
      detected between the frequency of centrosome abnormalities and chromosome
      instabilities. The AURKA AI was also associated with a lower expression of Ki-67,
      a higher expression of survivin, and the lack of expression of p16. These
      associations support our hypothesis that AURKA amplification contributes to
      pancreatic carcinogenesis by increasing chromosome instability and centrosome
      abnormality.

PMID- 15860352
TI  - Molecular characterization of a consistent 4.5-megabase deletion at 4q28 in
      prostate cancer cells.
AB  - Spectral karyotyping of prostate cell lines LNCaP, DU145, PC3, and 22RV
      demonstrated structural chromosome rearrangements involving the distal long arm
      of chromosome 4. In all but 22RV, these are nonreciprocal translocations between
      chromosomes 4 and 10. In 22RV, an apparently reciprocal t(2q;4q) is seen.
      Fluorescence in situ hybridization analysis of the chromosome 4 translocation
      breakpoints demonstrated that deletions were associated with all of the
      translocations, resulting in a net loss of chromosome material. Overlapping
      deletions in 4q28 approximately 34 were seen in LNCap, DU145, and 22RV, which
      defined an approximately 4.5-megabase pair common region of deletion. The
      deletion in PC3 was more proximal on 4q, involving the 4q21 approximately q26
      region. A meta analysis of high-resolution definition of losses of chromosome
      material from published studies demonstrates that loss of 4q material may occur
      in at least 50% of primary tumors. This analysis defines a series of genes in the
      critical 4q region, which is potentially associated with prostate tumor
      development.

PMID- 15860353
TI  - Microarray-based comparative genomic hybridization of pheochromocytoma cell lines
      from neurofibromatosis knockout mice reveals genetic alterations similar to those
      in human pheochromocytomas.
AB  - Somatic genetic aberrations have been identified in both sporadic
      pheochromocytomas and those associated with familial tumor syndromes; however,
      individual variations between human tumors and the absence of in vitro human
      pheochromocytoma models hinder efforts to understand the roles of those
      aberrations in tumorigenesis. Pheochromocytomas occur frequently in
      neurofibromatosis knockout mice and we have recently developed cell lines from
      those tumors. The availability of multiple tumors from genetically identical
      animals provides a powerful tool for understanding the pathobiology of
      pheochromocytomas. For the present investigation, we performed a genomic scanning
      analysis of four mouse pheochromocytoma cell lines by standard cytogenetics and
      microarray-based comparative genomic hybridization in order to identify genetic
      common denominators. All of the lines showed losses of most or all of chromosome
      9; three lines lost most or all of chromosome 4. Mouse chromosome 4 is homologous
      to human chromosome 1p, which is the most frequent deletion in human
      pheochromocytomas. Mouse chromosome 9 shows large areas of homology to human 3p,
      3q, and 11q, which are also frequently deleted. These comparisons suggest that
      genetic mechanisms in the genesis of pheochromocytomas may be similar across
      species. Additional changes that may be specific to this model included complete
      or partial gains of chromosome 12 as seen in 3 of the 4 lines analyzed by array
      CGH.

PMID- 15860354
TI  - Evidence for telomeric fusions as a mechanism for recurring structural
      aberrations of chromosome 11 in giant cell tumor of bone.
AB  - Giant cell tumor of bone (GCTB) is a benign but often aggressive tumor with a
      tendency toward local recurrence. Telomeric associations (tas) or telomeric
      fusions are common cytogenetic findings that have been implicated in the
      initiation of chromosome instability and tumorigenesis. We performed cytogenetic
      studies on 5 cases of GCTB to further characterize chromosome aberrations in
      these tumors. Four of the 5 cases showed abnormal karyotypes with clonal
      telomeric fusions involving chromosome 11. In 3 cases, the telomeric fusions of
      11pter were apparently the precursor lesions to the progression of sub-clones
      with structural chromosome aberrations of 11p. Two tumors demonstrated a similar
      pattern of progression resulting in whole arm losses of 11p, including sub-clones
      with both whole-arm unbalanced translocations and whole-arm deletions. A third
      tumor with clonal tas of 11pter showed 2 additional subclones, one with ring
      chromosome 11 and the other with an extra copy of 1q. To our knowledge, the 2
      cases with del(11)(p11) represent the first report of a recurring structural
      chromosome aberration in GCTB. These findings support the concept that telomeric
      instability is responsible for a large degree of intratumor heterogeneity and
      serves as a precursor lesion to subsequent clonal structural aberrations of
      chromosome 11 in GCTB.

PMID- 15860355
TI  - Frequent allelic loss of 21q11.1 approximately q21.1 region in advanced stage
      oral squamous cell carcinoma.
AB  - A fine mapping of loss of heterozygosity (LOH) was performed in oral squamous
      cell carcinoma (OSCC), using 12 markers on 21q11.1 approximately q21.1. We
      studied 43 resected primary invasive tumors and their paired normal tissues,
      concurrent dysplasia or carcinoma in situ in separate areas from 8 of the
      specimens, and 6 local recurrent carcinomas. LOH status was compared between
      lesions of different phases of progression within the same patient. A high
      frequency of LOH was observed for D21S1410, D21S120, and D21S1433 (60% each) in
      the primary lesions, constituting two interstitial deleted regions encompassing
      eight known genes. Cases showing LOH of D21S120 were significantly associated
      with advanced clinical stages (III and IV; P=0.02). Consistent allelic loss was
      observed in 64.2% of the informative cases between the precursor lesions and
      their corresponding invasive tumors, and in 59.5% of those between the primary
      lesions and their recurrent counterparts. Fewer than half of the different
      lesions within a given patient showed discordant allelic loss for tested markers.
      Our results suggest that 21q11.1 approximately q21.1 harbors tumor suppressor
      genes in OSCC. Genetic divergence may develop during tumor clone evolution.

PMID- 15860356
TI  - Association between the stages of cervical cancer and chromosome 1 aneusomy.
AB  - The high-risk human papillomavirus is known to play a pivotal role in cervical
      carcinogenesis. Numerical and structural aberrations are known to be related to
      different behaviors of malignant cervical lesions. The aims of this study were
      (1) to assess the number of cervical cells with chromosome 1 aneusomy (monosomy,
      trisomy, and tetrasomy) in 20 women with cervical intraepithelial neoplasia (CIN
      1, CIN 2, CIN 3, and invasive cancer) and three women without CIN by fluorescence
      in situ hybridization (FISH), (2) to determine the heterogeneity of aneusomy
      among women within each of the five groups studied, (3) to determine the
      association between the four progressive stages of cervical cancer and the number
      of cells with and without aneusomy, (4) to determine the association between
      number of cells with and without aneusomy and human papilloma virus (HPV)
      infection, and (5) to determine its usefulness as a biomarker of cancer risk. A
      hospital-based unmatched case-control study in a sample of 23 women grouped by
      disease stage and selected by histology from the Obstetrics and Gynecology
      Hospital of the Instituto Mexicano del Seguro Social (IMSS) in Mexico was
      conducted in 2002. Numerical aberrations of chromosome 1 in cervical smears were
      detected with FISH. HPV was detected with polymerase chain reaction (PCR) and
      typing was performed with restriction fragment length polymorphism (RFLPs).
      Analysis of chromosome 1 aneusomy revealed (1) homogeneity among women within
      each one of the five groups, (2) a positive linear trend between the aneusomy
      frequency and grade of lesion, and (3) an association between aneusomy and high
      risk HPV infection. These findings suggest the usefulness of the number of
      cervical cells with chromosome 1 aneusomy as a biomarker. In order to validate
      this biomarker we suggest a larger prospective study of cytological samples of
      patients with a longer follow-up.

PMID- 15860357
TI  - Association of functional polymorphisms of SLC11A1 with risk of esophageal cancer
      in the South African Colored population.
AB  - Several environmental factors have been implicated in the etiology of esophageal
      cancer (EC). The purpose of this study was to assess the likelihood that
      variation in the SLC11A1 gene contributes to EC susceptibility, possibly due to
      its role in inflammation and iron metabolism. The regions of the gene containing
      potential functional polymorphisms, including the promoter region and exon 2,
      were investigated. The study cohort included 105 EC South African Colored
      patients with squamous cell carcinoma (SCC) and 110 population-matched controls,
      with South African Colored referring to individuals of mixed ancestry. A
      significantly decreased frequency of the -237C-->T promoter polymorphism was
      observed in the patient group with EC compared with the population-matched
      control group (P < 0.002, chi(2) with Yates's correction=7.87). A statistically
      significant disease association was also observed with allele 3 of the 5'-(GT)n
      promoter polymorphism (P < 0.0006, chi(2) with Yates's correction=10.16), but
      only in the absence of the T-allele at nucleotide position -237 following allelic
      stratification. Four novel variants were identified in intron 1 (IVS1-28C-->T)
      and exon 2 (112G-->A, 148delGACCAGCCC, 157insGACCAGCCCAG). The novel intronic
      polymorphism, IVS1-28C-->T, was also significantly associated with EC (P < 0.05,
      chi(2) with Yates's correction=2.52). We demonstrate association of genetic
      variation in both the promoter region and intron 1 of the SLC11A1 gene with EC
      susceptibility.

PMID- 15860358
TI  - Progress in concurrent analysis of loss of heterozygosity and comparative genomic
      hybridization utilizing high density single nucleotide polymorphism arrays.
AB  - Genetic aberrations, such as deletions and amplifications are among the major
      pathogenetic mechanisms underlying many medical disorders. Analysis of
      chromosomal aberrations is particularly important in cancer research, where
      amplifications of oncogenes and deletions of tumor suppressor genes are major
      steps in the "multi-hit" process of tumorigenesis. Genome-wide molecular
      biological analyses, such as loss of heterozygosity (LOH) profiling and
      comparative genomic hybridization (CGH) have significantly enhanced our ability
      to detect chromosomal aberrations in cancer cells and assess their role in
      tumorigenesis. The recent introduction of high-density oligonucleotide arrays for
      measuring single nucleotide polymorphisms (SNP) has sparked a new wave of high
      resolution genetic mapping studies, including LOH and CGH applications on various
      cancer types. This review highlights recent progress on concurrent LOH and CGH
      analyses utilizing high density SNP arrays and their application in cancer
      research.

PMID- 15860359
TI  - Acquisition of a Ph chromosome with minor BCR/ABL fusion in treatment-related
      myelodysplastic syndrome with chromosome 7 abnormalities in a patient treated for
      Hodgkin disease.
AB  - The patient reported in this study originally had Hodgkin disease that was
      treated heavily with multiple courses of combined chemotherapy and radiotherapy.
      Secondary myelodysplastic syndrome (MDS) with a complex karyotype with monosomy
      7, deletion 7q31, and double deletion 7q31 developed 8 years later. During the
      course of the disease, conventional cytogenetics and interphase FISH (I-FISH)
      analysis detected a Ph chromosome and BCR/ABL fusion with mBCR rearrangement.
      Using a multiparametric cell scanning system that enables combined analysis with
      probes specific for 7/7q- and BCR/ABL in a single cell, we were able to
      demonstrate the presence of the BCR/ABL fusion only in cells with monosomy of
      chromosome 7 and 7q31 deletion, but not in cells with a normal chromosome 7 or
      with a double deletion of 7q31. We propose two possible models that may explain
      the appearance of the BCR/ABL fusion in the pre-existing treatment-related MDS
      clones characterized by chromosome 7 rearrangements.

PMID- 15860360
TI  - Cytogenetically unrelated clones in different histologic components of a Wilms
      tumor.
AB  - Wilms tumor (WT) is a triphasic malignant neoplasm comprised of variable
      proportions of epithelial, blastemal, and mesenchymal (stromal) elements.
      Cytogenetic analysis of these tumors has revealed a number of recurring
      abnormalities, including hyperdiploidy and structural abnormalities of
      chromosomes 1, 7, 11, and 16. We describe a WT in which apparently unrelated
      cytogenetic clones were detected at diagnosis, when the predominant histologic
      component was blastema, and after therapy, when the tumor was composed primarily
      of stroma. At diagnosis, a pseudodiploid karyotype was present, characterized by
      an X;14 insertion with concurrent deletion of 14q. In contrast, the post-therapy
      specimen had a hyperdiploid karyotype with a constellation of gains typical for
      WT. The presence of clonal abnormalities in both the blastemal and mesenchymal
      components of a WT supports the hypothesis that the stromal component is
      neoplastic, rather than reactive. The clonal abnormalities seen in different
      histologic components of the same WT are typically related or identical. The
      finding in this case of apparently unrelated clones is unusual. Possible
      etiologies for this biclonality, and clinical implications, are discussed.

PMID- 15860361
TI  - A new variant t(6;15;17)(q25;q22;q21) in acute promyelocytic leukemia:
      fluorescence in situ hybridization confirmation.
AB  - Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21),
      which results in the fusion of the promyelocytic leukemia (PML) gene at 15q22
      with the retinoic acid alpha-receptor (RARalpha) at 17q21. The 2 chimeric genes
      PML/RARalpha and RARalpha/PML are thought to play a role in leukemogenesis. We
      report a case of APL in a patient carrying an apparently complex variant
      translocation identified as t(6;15;17) by R-banding and whole chromosome 15 and
      17 painting. However, FISH analysis with a PML/RARalpha dual-color kit showed a
      more complex translocation, resulting presumably from a two-step rearrangement,
      with PML-RARalpha fusion gene located as expected on the der(15) but the residual
      5'-RARalpha signal located on the der(6). The patient achieved complete remission
      with all-trans retinoic acid treatment associated with chemotherapy. This case
      illustrates the usefulness of combined cytogenetics, FISH, and molecular biology
      to evidence the PML/RARalpha fusion gene in complex cases.

PMID- 15860362
TI  - Burkitt-type acute leukemia in a patient with B-prolymphocytic leukemia: evidence
      for a common origin.
AB  - Burkitt-type acute leukemia cells were present in the bone marrow of a patient
      with B-prolymphocytic leukemia diagnosed from peripheral blood cell morphology.
      Immunophenotype analysis confirmed morphological patterns. Cytogenetic and
      fluorescence in situ hybridization (FISH) analysis showed an identical
      t(8;22)(q24;q21) with MYC locus rearrangement in blood and bone marrow cells,
      with additional chromosome abnormalities in the bone marrow. In addition, the
      loss of one copy of the TP53 gene and identical IGH DNA clonal rearrangements
      were shown with FISH and polymerase chain reaction analysis respectively in the
      two types of leukemic cells. These data indicated the common origin of the two
      coexisting leukemias and are the first example of such occurrence in a leukemic
      patient.

PMID- 15860363
TI  - A variant t(8;10;21) in a patient with pathological features mimicking atypical
      chronic myeloid leukemia.
AB  - We report the case of an 11-year-old girl who was initially diagnosed with a
      chronic myeloproliferative disorder, possibly chronic myelogenous leukemia (CML),
      based on laboratory and blood and marrow morphological findings. The patient's
      high leukocyte count did not respond to hydroxyurea, a standard initial therapy
      for CML. Chromosomal analysis revealed that the patient did not have t(9;22), but
      a complex t(8;10;21)(q22;q24;q22), a variant of t(8;21). The treatment regime was
      switched to an acute myeloid leukemia (AML) protocol; the patient responded well
      and is now in remission. This case demonstrates again that routine clinical
      cytogenetic analysis plays an important role in the clinical diagnosis, guidance
      of treatment, and prognostication in hematological disorders.

PMID- 15860364
TI  - Genetic changes in localized prostate cancer of Japanese patients shown by
      comparative genomic hybridization.
AB  - To search for additional amplification and deletion sites that may serve as a
      starting point for the discovery of new oncogenes or tumor suppressor genes, 30
      Japanese localized prostate cancers were analyzed by comparative genomic
      hybridization (CGH) in this study. CGH was used to search for changes in DNA
      sequence copy-number in a series of 30 primary prostate adenocarcinomas,
      consisting of 22 cases of pT2N0 (organ confined; without capsular invasion) and 8
      cases of pT3N0 (with capsular invasion), removed by radical prostatectomy. CGH
      revealed that the shortest regions of overlap (SRO) of gains in pT2N0 were at
      8q22.2 approximately q24.2, 11q13.1 approximately q14.1, and 12q23 approximately
      q24.2, whereas the SRO of losses were seen at 8p23.3 approximately p22, 13q21.2
      approximately p22, and 18q21 approximately q22. The SRO of gains in pT3N0 were
      noted at 5q32 approximately q34, 8q22.3 approximately q24.1, 11q14.1
      approximately q22.3, and 12q22 approximately q24.2, whereas the SRO of losses
      were seen at 18q21.2 approximately q23. These results suggest that gains or
      losses of DNA in these regions are important for prostate cancer progression. The
      detection of the SRO may serve as a starting point to discover novel oncogenes
      and tumor suppressor genes involved in prostate cancer progression.

PMID- 15860365
TI  - Copy number gains on 22q13 in adenoid cystic carcinoma of the salivary gland
      revealed by comparative genomic hybridization and tissue microarray analysis.
AB  - Adenoid cystic carcinoma (ACC) of the salivary gland is a neoplasm characterized
      by slow but inevitable local progression and terminal hematogenous metastasis. To
      detect novel imbalanced chromosomal regions associated with tumorigenesis, we
      used chromosomal comparative genomic hybridization to screen 27 ACC. The most
      common aberration was copy number gain of 22q13 (nine cases) followed by gains of
      16p (seven cases) and 17q (four cases) and copy number losses on 6q (six cases).
      To further delineate the prevalence of 22q13 copy number gains in ACC,
      fluorescence in situ hybridization was performed for five bacterial/phage
      artificial chromosome (BAC/PAC) probes from the 22q13 consensus region with 57
      ACC on a tissue microarray. The overall prevalence of copy number gains on 22q13
      was 30% of the tumors in the fluorescence in situ hybridization analysis,
      irrespective of histologic differentiation (cribriform/tubular vs. solid) or
      tumor event (primary vs. recurrent). We therefore assume that copy number gain of
      22q13 is a novel frequent finding in ACC that may be involved in the initial
      pathogenesis of this neoplasm by proto-oncogene activation.

PMID- 15860366
TI  - Variant translocation t(2;21;8)(q36;q22;q22) with RUNX1/CBFA2T1 (AML1/ETO)
      transcript in a case of acute myelogenous leukemia.

PMID- 15860367
TI  - Androgen receptor-cofactor interactions as targets for new drug discovery.
AB  - Cofactor recruitment is a crucial regulatory step in nuclear receptor signal
      transduction. Given the obligate nature of interactions between cofactors and
      these receptors for transcriptional activity, it is likely that drugs that target
      coactivator interaction surfaces will function as pure antagonists with
      particular utility in the treatment of estrogen- and androgen-dependent cancers.
      Recent crystallographic analysis of one of the major protein-protein interaction
      surfaces on the androgen receptor has raised expectations that it will be
      possible to develop small-molecule antagonists that block cofactor interactions.

PMID- 15860368
TI  - Emerging role of the FGF system in psychiatric disorders.
AB  - Fibroblast growth factors (FGFs) comprise several peptides that, by interacting
      with a family of FGF receptors, participate in brain development and contribute
      to neuronal repair and plasticity. Recent evidence suggests that the expression
      of FGFs is altered in mood disorders and can be regulated by psychotropic drugs.
      This provides further support to the notion that neurotrophic molecules might
      have a role in the etiology and treatment of mental disorders.

PMID- 15860369
TI  - Calpain: a death protein that mediates progression of liver injury.
AB  - Calpain is a Ca(2+)-regulated cytosolic cysteine protease that exists mainly in
      two isoforms and mediates crucial cellular functions, including rearrangement of
      cytoskeletal proteins, transport of the glucose transporter GLUT4, and protein
      cleavage to activate various receptors and pro-enzymes. Unintentional activation
      or functional loss of intracellular calpain has been implicated in several
      pathologies, including neurodegenerative diseases, traumatic brain and spinal
      cord injuries, cataracts and ischemia-associated injuries. Furthermore,
      polymorphism in the gene encoding calpain-10 has been associated with increased
      risk of type 2 diabetes. Recent studies have revealed a novel role for calpain in
      the progression of toxicant-induced liver damage. Evidence suggests that calpain
      leaking out of necrotic hepatocytes is highly activated in the extracellular
      milieu and hydrolyzes proteins in the plasma membrane of neighboring cells
      leading to progression of injury. Experimental intervention with calpain
      inhibitors substantially mitigates progression of liver injury initiated by
      toxicants, thereby preventing acute liver failure, and toxicant-induced animal
      death, pointing to a new potential therapeutic strategy against acute toxicities.

PMID- 15860370
TI  - Stimulants and the developing brain.
AB  - For almost 70 years, children have received stimulants for the treatment of
      attention deficit hyperactivity disorder [ADHD (initially called hyperkinetic
      syndrome)], with little understanding of the long-term effects of these drugs on
      brain development. The maturation and refinement of the brain during childhood
      and adolescence, including the overproduction and selective elimination of
      synapses, is based on genetic programming and experience. The effects of
      stimulant drugs during different stages of this process have unique short-term,
      acute effects that also influence their long-term effects. Chronic, pre-pubertal
      exposure alters the expected developmental trajectory of brain structure and
      function and results in a different topography in adulthood. The timing of
      exposure (childhood versus adolescence), the age of examination after drug
      exposure (immediately or delayed into adulthood) and sex influence the observable
      effects. Preclinical studies of the effects of stimulant exposure provide
      increased understanding about the impact of stimulant drugs on brain development
      and provide insight into new treatment options for ADHD and other disorders of
      childhood.

PMID- 15860371
TI  - PPARs: therapeutic targets for metabolic disease.
AB  - The three peroxisome-proliferator-activated receptor (PPAR) subtypes, PPAR-gamma,
      PPAR-alpha and PPAR-delta, are nuclear receptors that have been the focus of
      extensive research during the past decade. These receptors function as lipid
      sensors that coordinately regulate the expression of large gene arrays and,
      thereby, modulate important metabolic events. They are also the targets of drugs
      that are effective in the treatment of metabolic disorders (type 2 diabetes
      mellitus and atherosclerosis) that afflict industrialized societies at epidemic
      levels. Ongoing research indicates that modulation of PPAR activity might be an
      effective therapy for additional maladies associated with the metabolic syndrome,
      including obesity. Novel PPAR ligands are now being developed that possess
      broader efficacies and improved tolerability compared with currently available
      therapeutic agents.

PMID- 15860372
TI  - Immunotherapeutic potential for ceramide-based activators of iNKT cells.
AB  - Invariant natural killer T (iNKT) cells are a subpopulation of T cells that are
      reactive with glycolipids that are bound by CD1d antigen-presenting molecules.
      alpha-Galactosylceramide (alpha-GalCer) is a synthetic glycolipid that is a
      potential treatment for several autoimmune diseases, infectious diseases and
      cancer. Its therapeutic effect can be traced back to its ability to bind CD1d and
      activate iNKT cells, which results in the production of T helper 1 (Th1) and Th2
      cytokines. However, the effectiveness of alpha-GalCer therapy is limited by the
      opposing actions of Th1 and Th2 cytokines. The alpha-GalCer analogs OCH and the
      recently designed and synthesized C-glycosidic alpha-GalCer selectively activate
      one of two types of cytokine profiles, possibly because either reduced or
      enhanced overall stability of the CD1d-glycolipid-T-cell-receptor complex leads
      to a higher potency in vivo, compared with the parent compound. These discoveries
      boost the potential of glycolipid-based therapies.

PMID- 15860373
TI  - Mitochondria are sensors for HIV drugs.
AB  - Highly active anti-retroviral therapy (HAART) has drastically altered the course
      of HIV-1 infection, resulting in a major decrease in morbidity and mortality.
      However, adverse drug reactions and long-term toxicities associated with HAART
      are now a concern. A major toxicity that has been highlighted by the increased
      use of HAART is related to mitochondrial side-effects. At the same time, analysis
      of the biochemical pathways involved in programmed cell death has revealed that
      mitochondria are main sensors in this process. In this article, the regulation of
      mitochondrial damage following the use of nucleoside analogue reverse
      transcriptase inhibitors (NRTIs) and protease inhibitors is discussed, with a
      particular focus on the putative molecular mechanisms involved.

PMID- 15860374
TI  - Yeast as a model for medical and medicinal research.
AB  - In the past, studies using the yeast Saccharomyces cerevisiae enabled major
      breakthroughs in the understanding of basic cellular and molecular processes.
      Today, the use of yeast is undergoing a "rebirth" in both fundamental and applied
      research. Indeed, advances in yeast technology have paved the way for a variety
      of new genome-wide screening approaches. Experimental strategies using yeast aim
      to unravel disease-related molecular events and to discover novel medicinal
      compounds. In this article, the impact of yeast as an experimental tool for
      disease-related studies is summarized and the use of yeast in high-throughput
      screenings for pharmacological purposes is evaluated. The recently applied and
      promising approach of so-called humanized yeast systems is also discussed.

PMID- 15860375
TI  - A renaissance in trace amines inspired by a novel GPCR family.
AB  - Trace amines (TAs) are endogenous compounds that are related to biogenic amine
      neurotransmitters and are present in the mammalian nervous system in trace
      amounts. Although their pronounced pharmacological effects and tight link to
      major human disorders such as depression and schizophrenia have been studied for
      decades, the understanding of their molecular mode of action remained incomplete
      because of the apparent absence of specialized receptors. However, the recent
      discovery of a novel family of G-protein-coupled receptors (GPCRs) that includes
      individual members that are highly specific for TAs indicates a potential role
      for TAs as vertebrate neurotransmitters or neuromodulators, although the majority
      of these GPCRs so far have not been demonstrated to be activated by TAs. The
      unique pharmacology and expression pattern of these receptors make them prime
      candidates for targets in drug development in the context of several neurological
      diseases. Current research focuses on dissecting their molecular pharmacology and
      on the identification of endogenous ligands for the apparently TA-insensitive
      members of this receptor family.

PMID- 15860376
TI  - Treatment of refractory angina pectoris.
AB  - Refractory angina pectoris is defined as Canadian Cardiovascular Society class
      III or IV angina, where there is marked limitation of ordinary physical activity
      or inability to perform ordinary physical activity without discomfort, with an
      objective evidence of myocardial ischemia and persistence of symptoms despite
      optimal medical therapy, life style modification treatments, and
      revascularization therapies. The patients with refractory angina pectoris may
      have diffuse coronary artery disease, multiple distal coronary stenoses, and or
      small coronary arteries. In addition, a substantial portion of these patients
      cannot achieve complete revascularization and continue to experience residual
      anginal symptoms that may impair quality of their life and increase morbidity.
      This represents an end-stage coronary artery disease characterized by a severe
      myocardial insufficiency usually with impaired left ventricular function. As the
      life expectancy is increasing, patients with angina pectoris refractory to
      conventional antianginal therapeutics are a challenging problem. We review the
      nonconventional therapies to treat the refractory angina pectoris, including
      pharmacotherapy, therapeutic angiogenesis, transcutaneus electrical nerve and
      spinal cord stimulation, enhanced external counterpulsation, surgical
      transmyocardial laser revascularization, percutaneous transmyocardial laser
      revascularization, percutaneous in situ coronary venous arterializations, and
      percutaneous in situ coronary artery bypass. These therapies are not supported by
      a large body of data and have only a complementary role; therefore, the
      aggressive traditional and proven treatment of angina pectoris should be
      continued along with these therapies, used on an individual basis.

PMID- 15860377
TI  - Statins' dosage in patients with renal failure and cyclosporine drug-drug
      interactions in transplant recipient patients.
AB  - Dyslipidemia is frequent in patients with renal failure and in transplant
      recipient patients. This lead to a wide use of 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with impaired
      renal function or in patients treated with cyclosporine as post-transplantation
      immunosuppressive therapy. As a result, it is crucial for those patients'
      physicians to be aware of how to handle these drugs when renal function is
      impaired and/or when cyclosporine is co-administered. Most statins have an
      extensive hepatic elimination and the renal route is usually a minor elimination
      pathway. However, pharmacokinetic alterations have been described for some of
      these drugs in patients with renal insufficiency. Cyclosporine is a widely used
      immunosuppresive therapy in solid organ transplant patients and drug-drug
      interactions are likely to occur when statins and cyclosporine are administered
      together. Those interactions may theoretically result in increased statins and/or
      cyclosporine serum levels with potential muscle and/or renal toxicity. As a
      result, caution is warranted if concurrent administration is performed. In this
      review, we synthesized the data from the literature on (1) the pharmacokinetics
      and dosage adjustment of atorvastatin, fluvastatin, pravastatin, rosuvastatin,
      and simvastatin in patients with renal failure and (2) the potential drug-drug
      interactions between these drugs and cyclosporine in transplant recipient
      patients.

PMID- 15860378
TI  - Risk factors for thromboembolic events in renal failure.
AB  - OBJECTIVES: To determine whether prior thromboembolic events (TE) influence
      current measures of hemostasis, inflammation and oxidative stress in a population
      at high cardiovascular risk. BACKGROUND: Renal failure patients demonstrate a
      remarkably elevated incidence of TE. METHODS: Relationships between plasma test
      results and prior TE history were studied in 78 diabetic and 23 non-diabetic
      patients with renal failure. TE were defined as myocardial infarction, stroke or
      vascular surgery. RESULTS: Markers for inflammation (interleukin (IL)-6, C
      reactive protein (CRP)), thrombosis (fibrinogen, low molecular weight (LMW)
      fibrinogen, factor VII, viscosity), fibrinolysis (fibrinolytic activity,
      plasminogen activator inhibitor (PAI)), endothelial/platelet activity (P
      selectin, von Willebrand factor (vWf)) and oxidative stress (antibody to oxidized
      low-density lipoprotein (LDL), advanced glycated end products) were significantly
      different from a healthy control population. Dialysis patients with diabetes were
      twice as likely to have sustained a TE (58 vs. 30%, p = 0.032). Those patients in
      the total group with levels above the median for IL-6 (p = 0.045), and CRP (p <
      0.017) were more likely to have sustained a TE than those with levels below the
      median. Those diabetic patients with levels above the median for CRP were more
      likely to have a prior history of TE (p < 0.021). For non-diabetic patients,
      levels above the median of IL-6 were associated with a prior history of TE (p =
      0.027). Multiple correlations for factors of inflammation, hemostasis and
      oxidative stress indicate that these mechanisms are not independent of one
      another. CONCLUSION: Prior TE was associated with markers of inflammation a
      relationship that may influence the interpretation of these tests which are
      strongly interrelated in patients at high cardiovascular risk.

PMID- 15860379
TI  - False-positive troponin I measured with the Abbott AxSYM attributed to fibrin
      interference.
AB  - BACKGROUND: Serum is often used for the measurement of cardiac troponin I (cTnI).
      Previous reports suggest that fibrin present in serum samples collected for cTnI
      analysis may interfere with measurement of this marker. We investigated the
      incidence and magnitude of fibrin interference in serum specimens submitted for
      cTnI measurement using the AxSYM analyzer by performing duplicate analysis of all
      specimens with increased cTnI results. METHODS: Over a 4-month period, we
      analyzed 3692 specimens for cTnI with the Abbott AxSYM. Of these, 307 (8.3%)
      showed increased cTnI. A threshold of three times the precision of the method
      (15%) was used to judge discrepancies between duplicate analyses of specimens;
      all specimens being recentrifuged between the initial and repeat cTnI analyses.
      RESULTS: Of 307 patient specimens with elevated cTnI concentrations, 24 (7.8%)
      demonstrated differences of greater than 45% between duplicate analyses.
      Concentrations of cTnI obtained on initial analysis of these 24 specimens ranged
      from 2.4 to 24.0 microg/l. Repeat analysis showed the repeat values for 20 (83%)
      to be within the normal reference interval, with 16 (67%) showing concentrations
      of less than 0.3 microg/l. CONCLUSIONS: Our finding indicates that interference
      should be highly suspected in serum specimens where the initially measured cTnI
      concentrations is in the range of 2.0-25.0 microg/l when using the Abbott AxSYM.
      The finding of no interference in specimens with measured troponin concentration
      greater than 25.0 microg/l suggests that the interference effect of fibrin is
      generally not sufficient to cause spurious elevations of cTnI into this range. In
      addition, since switching to plasma as the specimen of choice for the AxSYM, we
      have not observed any discrepant cTnI results following duplicate analysis of
      over 200 patient samples with initial measured cTnI concentrations of 2.0
      microg/l or greater.

PMID- 15860380
TI  - Early detection of cardiac dysfunction in patients with anorexia nervosa by
      tissue Doppler imaging.
AB  - BACKGROUND: Cardiac damage is a major complication of chronic starvation. The aim
      of this study was to evaluate the changes of left ventricular function in
      patients with anorexia nervosa by means of pulsed tissue Doppler imaging.
      METHODS: A total of 20 females (age 22.4+/-4.3 years) with overt anorexia
      nervosa, 20 matched healthy thin females with body mass index < 19 kg/m2 and 20
      matched healthy normal-weight females underwent both standard echocardiography
      and tissue Doppler imaging. Myocardial systolic wave (Sm) and early (Em) and
      atrial (Am) diastolic waves were measured on the basal lateral segment and the
      basal interventricular septum from the apical four-chamber view. RESULTS: When
      compared with control groups, the anorexia nervosa group showed lower left
      ventricular mass (p < 0.0001), lower Sm peak of both lateral wall (6.5+/-0.9 vs.
      9.4+/-2.1 and vs. 9.5+/-1.9 cm/sec, p < 0.001) and septum (5.6+/-1.5 vs. 8.6+/
      1.6 and vs. 8.8+/-1.5 cm/sec, p < 0.001), and comparable Em, Am and Em/Am ratio.
      The ratio between transmitral peak E and Em was significantly greater in anorexic
      patients than in controls (lateral wall: 8.1+/-0.1 vs. 6.8+/-0.2 and vs. 6.9+/
      0.2, p < 0.001; septum: 10.8+/-0.4 vs. 8.8+/-0.5 and vs. 8.8+/-0.3, p < 0.001).
      No differences were observed between thin and normal-weight females. In the
      anorexia nervosa group, S(m) peak was significantly related to left ventricular
      mass indexed, at both septum (r = 0.55, p < 0.02) and lateral wall (r = 0.49, p <
      0.03) levels. CONCLUSIONS: These results show that anorexia nervosa is associated
      with left ventricular systolic dysfunction, which is related with the reduction
      of cardiac mass. Tissue Doppler imaging can give useful information in the
      identification of regional left ventricular dysfunction, in addition to
      traditional parameters.

PMID- 15860381
TI  - Is there an independent association between waist-to-hip ratio and cardiovascular
      risk factors in overweight and obese women?
AB  - BACKGROUND: This study was conducted to evaluate the relationship between waist
      to-hip ratio (WHR) and cardiovascular risk factors in overweight and obese women
      and to determine a point of WHR above which the chances of having cardiovascular
      risk factors increased. METHODS: In this cross-sectional study, 2892 pre- and
      postmenopausal women aged 20-78 years with body mass index (BMI) > or = 25
      selected from among 5791 women of the Tehran Lipid and Glucose Study (TLGS)
      population (n = 15,005), by multistage cluster random sampling method, were
      included. Anthropometric indices were measured and BMI and WHR were calculated.
      Blood pressure was evaluated according to standard protocols. Biochemical indices
      were measured in the fasting state. Subjects were placed into the high-risk
      categories for cardiovascular disease on the basis of population-defined norms.
      Women were divided into quartiles based on their WHR: quartile 1: < 0.78,
      quartile 2: 0.78- < 0.83, quartile 3: 0.83- < 0.88, quartile 4: > or = 0.88 for
      premenopausal women, and quartile 1: < 0.84, quartile 2: 0.84- < 0.9, quartile 3:
      0.9- < 0.94 and quartile 4: > or = 0.94 for postmenopausal women. RESULTS: A
      lower proportion of pre- and postmenopausal women with BMI > or = 35 were in
      quartile 1 and a higher proportion in quartile 4. A significant increasing trend
      was observed for odds ratio of having low HDL-C, high triglyceride, high total
      /HDL-cholesterol and high fasting blood sugar (FBS) with increasing WHR.
      Controlling for BMI and simultaneously adjusting for confounding variables had no
      effect on this trend. Although no significant increasing trends were seen for
      having high total cholesterol, LDL-cholesterol, systolic and diastolic blood
      pressure with quartiles of WHR in both pre- and postmenopausal women, subjects
      with higher quartiles of WHR still had higher chances for having high total
      cholesterol. In the case of postmenopausal women having of higher odds for high
      LDL-cholesterol and high systolic blood pressure in the fourth quartile of WHR
      should also be added to the high total cholesterol. CONCLUSION: The results
      showed that in overweight and obese women, chances of having cardiovascular risk
      factors increased with WHR > or = 0.78 for premenopausal and with WHR > or = 0.84
      for postmenopausal women.

PMID- 15860382
TI  - Changes in left atrial size in patients with persistent atrial fibrillation: a
      prospective echocardiographic study with a 5-year follow-up period.
AB  - Atrial fibrillation (AF) is a common arrhythmia, occurring in 0.4% of the general
      population. AF has been shown to be associated with left atrial enlargement,
      which is considered both a cause and a consequence of the arrhythmia. The aim of
      the study was to determine the influence of AF on changes in
      echocardiographically determined left atrial (LA) size, during 5 year follow-up
      period, in a population with well-controlled hypertension, free from structural
      heart disease, except mild left ventricle thickening, and with an absence of
      other potential causes of atrial enlargement. The study group, comprised of 81
      patients with persistent AF, with underlying hypertensive heart disease,
      consecutively referred for elective direct current cardioversion. The mean age of
      the study population was 59.3+/-8.4 years (ranged from 43 to 80), a mean AF
      duration was 8.8+/-8.7 months (ranged from 1 to 30 months). The patients
      underwent two-dimensional echocardiography to determine left atrial size, before
      and 5 years after cardioversion. Twenty out of eighty-one cardioverted patients
      maintained sinus rhythm 5 years after cardioversion (25%). In this group
      anteroposterior LA dimension and LA volume decreased from a mean (+/-S.D.) 49.7+/
      4.5 to 46.8+/-4.8 mm (-6%, p < 0.05) and from 103.6+/-28.8 to 91.1+/-18.3 cm2 (
      9.2%, p < 0.05), respectively. Left ventricle ejection fraction increased from
      52.8+/-6.3% to 60.0+/-4.0% (p < 0.05) and clinical stage improved in patients who
      maintained sinus rhythm through 5 years. In contrast, in the AF group,
      anteroposterior LA dimension and LA volume increased from 46.6+/-4.3 to 48.1+/
      5.6 mm, and from 91.3+/-20 to 103+/-34 cm2 (by an average 3.3% and 14.3%,
      respectively), at the end of study. When divided into two groups: Imid R:II and
      III NYHA class, in AF patients LA volume increased by an 21.4% in the III NYHA
      class and 7.3% in the Imid R:II NYHA class. Left ventricular ejection fraction
      did not change between the two echocardiographic studies in the AF group (44.9+/
      14.3% vs. 44.6+/-12.9%, Ns). In conclusion, it has been proved that AF occurring
      in patients with hypertensive heart disease causes a slow and progressive
      increase in LA size especially in patients in functional III NYHA class, and that
      the maintenance of sinus rhythm partially reverts the process of LA enlargement
      in patients with well-controlled hypertension, a history of AF and successfully
      treated for AF.

PMID- 15860383
TI  - Oxidative stress and fibrosis in incipient myocardial dysfunction in type 2
      diabetic patients.
AB  - BACKGROUND: The existence of a diabetic cardiomyopathy has been recently
      supported by epidemiological studies. Increased oxidative stress and myocardial
      fibrosis has been hypothesized as etiopathogenic mechanisms. We sought to
      demonstrate the existence of incipient myocardial dysfunction in type 2 diabetes
      and its relation with markers of oxidative stress and myocardial fibrosis.
      METHODS: We studied by echocardiography 25 uncomplicated type 2 diabetic patients
      and 12 sex- and age-matched control subjects. Stress-corrected endocardial and
      midwall shortening and systolic and early diastolic velocity of the lateral
      mitral annulus (Doppler tissue) were used as parameters of myocardial function.
      Serum levels of glutathione peroxidase and procollagen type I carboxy-terminal
      peptide were used as markers of oxidative stress and myocardial fibrosis,
      respectively. RESULTS: Diabetics had significant lower values of corrected
      endocardial shortening than control subjects (P = 0.029). Both systolic and early
      diastolic mitral annulus velocities were significantly reduced in diabetics as
      compared to control subjects (P = 0.008 and P = 0.003, respectively). In diabetic
      patients, corrected endocardial (r = -0.56) and midwall shortening (r = -0.38)
      correlated with procollagen type I carboxy-terminal peptide, whereas systolic and
      early diastolic velocities of the mitral annulus correlated with glutathione
      peroxidase (both r = 0.44). CONCLUSIONS: In a highly selected group of
      uncomplicated type 2 diabetic patients, we found evidence of systolic and
      diastolic myocardial dysfunction, especially with the use of pulsed Doppler
      tissue imaging. The correlations between parameters of myocardial function and
      glutathione peroxidase and procollagen type I carboxy-terminal peptide support a
      mechanistic role for the increased oxidative stress and myocardial fibrosis in
      the myocardial dysfunction of type 2 diabetes.

PMID- 15860384
TI  - The relationship between blood pressure, pulse pressure and right ventricular
      function following an atrial switch procedure for complete transposition of the
      great arteries.
AB  - BACKGROUND: The pressure overload may be responsible for the failure of the
      systemic ventricle. No study so far has evaluated the association between
      arterial blood pressure values and right ventricular function in adults with
      atrially corrected complete transposition. METHODS: This was a retrospective
      analysis. The studied population consisted of 60 patients with complete
      transposition, 11.5+/-2.7 years after atrial switch procedure, divided into
      subgroups according to the severity of systemic ventricular dysfunction (right
      ventricular ejection fraction < or = 0.40 vs. > 0.40), and the severity of
      perfusion abnormalities in the radionuclide study (absent or mild vs. moderate-to
      severe). RESULTS: All patients had blood pressure values (systolic 109.1+/-11.7
      mm Hg and diastolic 72.3+/-9.7 mm Hg) within the normal range. Systolic blood
      pressure values correlated inversely with right ventricular ejection fraction (r
      = -0.450; p < 0.001). Compared to patients with systolic blood pressure below
      median values, patients with "elevated" blood pressure had lower right
      ventricular ejection fraction (32.6+/-6.3 vs. 38.9.+/-7.2; p < or = 0.002) and
      more significant perfusion abnormalities (1.5+/-1.0 vs. 2.9+/-1.5; p < or =
      0.001). In a multivariate backward logistic regression model age at surgery and
      at the time of the study, systolic blood pressure at rest predicted impaired
      right ventricular ejection fraction (p < 0.02). Greater pulse pressure at peak
      exercise female sex were associated with greater more severe perfusion
      abnormalities (p < 0.01). CONCLUSIONS: There is a significant correlation between
      blood pressure values and indices of right ventricular dysfunction in patients
      who underwent an atrial switch procedure for complete transposition. Blood
      pressure values might be considered as a surrogate end point in these patients.

PMID- 15860385
TI  - Rapid effect of pravastatin on endothelial function and lipid peroxidation in
      unstable angina.
AB  - BACKGROUND: Oxidative stress contributes to endothelial dysfunction, an important
      step to the pathogenesis of atherosclerosis and coronary events. Latest studies
      revealed the existence of pleiotropic and especially antioxidant properties of
      statins. We sought to examine the effects of pravastatin on lipid peroxidation
      and endothelial function, independently from lipid-lowering, in patients with
      unstable angina (UA). METHODS: Thirty-seven patients (males), 64.46+/-9.09 years,
      suffering from UA enrolled in the study. Patients were not on statin medication
      before admission and they received after randomization either 40 mg pravastatin
      daily (group A, n = 20), or placebo (group B, n = 17). Malondialdehyde (MDA)
      concentration, an index of lipid peroxidation and plaque instability, flow
      mediated dilatation (FMD) of the brachial artery and blood lipids were measured
      on the second day of hospitalization and 10 days later. RESULTS: MDA decreased
      significantly in both groups (A, p = 0.008; B, p = 0.003). FMD increased
      significantly in group A (p = 0.007), whereas in group B it did not change. Serum
      lipids remained unaltered in all three groups. CONCLUSIONS: Pravastatin
      administration improved FMD within 10 days and this favorable effect occurred
      before any significant reduction in blood lipids, revealing its pleiotropic
      effects during the early phase of an acute coronary syndrome. Circulating lipid
      peroxidation products in patients with UA decreased significantly during the same
      period independently of endothelial function and pravastatin therapy.

PMID- 15860386
TI  - Prevalence of aspirin resistance measured by PFA-100.
AB  - BACKGROUND: Aspirin protects from cardiovascular events. However, a number of
      patients who take this drug suffer events, probably due to aspirin resistance.
      Our objective was to determine the prevalence of aspirin resistance in patients
      taking this drug and to test if resistance is related to different variables.
      METHODS: Platelet function was studied in 113 patients (90 men) aged 63+/-9 (80
      with stable ischaemic heart disease) who took aspirin (100 to 300 mg/day). By a
      platelet function analyzer, called PFA-100, the epinephrine closure time was
      studied. We also analysed the possible relationship between epinephrine closure
      time and the following variables: total cholesterol, LDL, HDL cholesterol,
      total/HDL cholesterol, triglycerides, lipoprotein(a), and C reactive protein. The
      possible association between aspirin resistance (epinephrine closure time <161 s)
      and different variables was also analyzed with the SPSS statistical package.
      Results are expressed in median (interquartile range). RESULTS: Aspirin
      resistance was found in 32% of cases. Ischaemic heart disease, smoking habit, and
      treatment with statins were associated with a significantly greater percent of
      resistance (p=0.049, 0.009, and 0.043, respectively). Patients with aspirin
      resistance had higher levels of total/HDL cholesterol: 4.46 (3.76-5.55) vs. 3.97
      (3.20-4.75) (p = 0.023); and lipoprotein(a): 57.2 (24.8-85.0) mg/dl vs. 13.1 (3.7
      38.0) mg/dl (p = 0.007). CONCLUSIONS: Aspirin resistance is frequent and easily
      detected by PFA-100. It occurs more frequently in smokers. A mild association is
      found with ischaemic heart disease, some lipids, and treatment with statins. Our
      results support the applicability of this method to clinical practice.

PMID- 15860387
TI  - Secondary prevention after cryptogenic cerebrovascular events in patients with
      patent foramen ovale.
AB  - BACKGROUND: Patients with patent foramen ovale and cryptogenic stroke are at risk
      of recurrence, but there are few data on strategies to prevent this. METHODS: We
      studied 280 consecutive patients with cryptogenic cerebrovascular events and a
      patent foramen ovale examined by multiplane transesophageal echocardiography.
      Patients received platelet inhibitors (n = 66) or anticoagulation (n = 47) or
      underwent device closure (n = 167). During the mean follow-up of 2.6 years, we
      compared the frequency of recurrent events, death and severe treatment
      complications. RESULTS: A total of 33 (12%) patients had a recurrent
      cerebrovascular event. The annual recurrence rates were 13% in patients treated
      with platelet inhibitors, 5.6% in those on oral anticoagulation, and 0.6% in
      those after device closure. Independent predictors of recurrent cerebrovascular
      events were a patent foramen ovale larger than 4 mm (hazard ratio 3.8, 95% CI 1.2
      11.2; p = 0.017) or previous strokes (hazard ratio 4.3, 95% CI 2.0-9.2; p <
      0.001). Interventional closure of the patent foramen ovale decreased the risk of
      a recurrent event compared with oral anticoagulation (hazard ratio 0.06, 95% CI
      0.12-0.29; p < 0.001), whereas antiplatelet therapy showed a trend to an
      increased risk (hazard ratio 2.3; 95% CI 0.9-5.5; p = 0.055). Major side effects
      occurred in 7 anticoagulated patients and in 13 patients after device closure.
      There were two non-vascular deaths and one fatal hemorrhagic stroke. CONCLUSIONS:
      Patients with a large patent foramen ovale and a cryptogenic cerebrovascular
      event had a substantial risk of recurrence even with medical treatment. Risk of
      recurrence was lower after device closure of the patent foramen ovale.

PMID- 15860388
TI  - Effects of short-term moderate exercise training on sexual function in male
      patients with chronic stable heart failure.
AB  - BACKGROUND: Patients with chronic heart failure (CHF) have sexual dysfunction
      that impairs quality of life. Recent trials have demonstrated that exercise
      training (ET) improves quality of life (QOL) of CHF patients, but it is not
      established whether this benefit may be associated with an improvement in sexual
      dysfunction. OBJECTIVE: To determine whether ET can improve sexual dysfunction in
      patients with CHF. METHODS: We prospectively studied 59 male patients (57+/-9
      years) with stable CHF in sinus rhythm and without prostatic disease. Patients
      were randomized into two groups. A group (T, n = 30) underwent supervised cycle
      ergometer ET at 60% of peak VO2, three times a week, 60 min each session, for 8
      weeks. A group (NT, n = 29) was not exercised. Medications were not changed
      during the study. On study entry and at 8 weeks all patients underwent a symptom
      limited cardiopulmonary exercise testing, brachial artery endothelium-dependent
      (ED) and endothelium-independent (EI) vasomotor responses, QOL and sexual
      activity profile assessment (SAP) by questionnaire. RESULTS: At 8 weeks, no
      changes were observed in control patients. In trained patients, however, peak VO2
      improved by 18% (P < 0.005) and was correlated with QOL (r = 0.80; P < 0.001).
      Flow-mediated dilation improved in trained patients (from 2.29+/-1.13% to 5.04+/
      1.7%, P = 0.0001), while EI dilation (after 0.3 mg sublingual NTG) did not. In
      group T, all three domains (i.e. Domain 1=relationship with the partner; Domain 2
      = quality of penile erection; Domain 3 = personal wellness) were significantly
      improved from baseline (total score patients: from 3.49+/-3.4 to 6.17+/-3.2, P <
      0.001; partners: from 2.47+/-2.7 to 4.87+/-2.5, P < 0.001). Pre-post training
      change in SAP total score was correlated with changes in coronary risk profile (r
      = -0.49; P = 0.01), peak VO2 (r = 0.67; P < 0.001) and QOL (r = 0.73; P = 0.01).
      Multivariate analysis selected the improvement in ED-vasomotor response as the
      strongest independent predictor of SAP improvement (r = 0.63, P < 0.001).
      CONCLUSIONS: In stable CHF, cycle ergometer ET significantly improves brachial
      artery endothelial dysfunction, suggesting a systemic effect of leg exercise.
      This benefit was correlated with improvements in sexual activity.

PMID- 15860389
TI  - Effects of right bundle branch block during atrioventricular nodal reentrant
      tachycardia.
AB  - BACKGROUND: The significant role of bundle branch block during atrioventricular
      nodal reentrant tachycardia (AVNRT) is not clear. The purposes of this study were
      to study the effects of complete right bundle branch block (RBBB) on
      electrophysiological parameters during AVNRT and to define the significance of
      complete RBBB during AVNRT. METHODS AND RESULTS: According to characteristics of
      electrocardiogram during sinus rhythm and AVNRT, 50 patients who underwent
      catheter ablation for slow-fast AVNRT were divided into three groups. Group I
      included 20 patients who had narrow QRS (< or = 110 ms) during sinus rhythm and
      AVNRT. Group II included 18 patients who had persistent RBBB (< or = 120 ms)
      during sinus rhythm and AVNRT. Group III included 12 patients who had narrow QRS
      during sinus rhythm, but they had narrow QRS and transient RBBB during AVNRT. The
      atrio-His (AH) interval (296+/-60 vs. 288+/-75 ms), His-ventricular (HV) interval
      (36+/-11 vs. 35+/-11 ms), His-atrial (HA) interval (72+/-24 vs. 71+/-28 ms),
      VA(HRA) interval (defined as the interval between the onset of ventricular
      depolarization and the onset of atrial activity of right high atrium; 34+/-24 vs.
      37+/-25 ms), VA(CSO) interval (defined as the interval between the onset of
      ventricular depolarization and the onset of atrial activity of coronary sinus
      ostium; 13+/-28 vs. 26+/-23 ms) and tachycardia cycle length (TCL; 368+/-67 vs.
      359+/-73 ms) during AVNRT were similar between group I and group II (all P >
      0.05). In group III, the AH interval (255+/-81 vs. 246+/-83 ms), HV interval
      (44+/-5 vs. 42+/-11 ms), HA interval (66+/-19 vs. 70+/-15 ms), VA(HRA) interval
      (27+/-15 vs. 29+/-16 ms), VA(CSO) interval (23+/-25 vs. 21+/-25 ms) and TCL
      (322+/-76 vs. 316+/-77 ms) were not significantly different between AVNRT with
      narrow QRS and those with transient RBBB (all P > 0.05). CONCLUSIONS: Persistent
      RBBB and transient RBBB have no significant effects on the electrophysiological
      parameters during AVNRT. These findings suggest that RBBB might not influence the
      conduction of lower common pathway or the circuit of AVNRT.

PMID- 15860391
TI  - The relationship between sex hormones and lipid profile in men with coronary
      artery disease.
AB  - BACKGROUND: Men are more prone to develop coronary artery disease (CAD) than
      women and the mechanism of this different susceptibility is not well elucidated.
      The aim of this study was to evaluate the relationship between serum levels of
      several sex hormones and serum levels of lipoproteins, as well as the association
      between sex hormones and clinical covariates in men with stable coronary artery
      disease. METHODS: Study population consisted of 111 men (mean age 55 years) with
      stable coronary artery disease. In all patients levels of testosterone,
      dehydroepiandrosterone sulfate (DHEA-S), estradiol, sex hormone binding globuline
      (SHBG), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were
      measured and free testosterone index (FTI) was calculated knowing SHBG. Standard
      lipid analysis included total cholesterol, HDL-cholesterol, LDL-cholesterol, and
      triglycerides. The extent of coronary artery disease was defined using
      semiquantitative coronary angiography score. RESULTS: Significant positive
      correlations were found between estradiol levels and levels of total cholesterol
      (r = 0.31; p = 0.005), LDL-cholesterol (r = 0.32; p=0.004), total cholesterol/HDL
      ratio (r = 0.26; p = 0.020), and triglycerides (r = 0.24; p = 0.030), whereas no
      significant association was found between levels of these lipids and testosterone
      or DHEA levels. HDL cholesterol showed a significant association with levels of
      FSH (r = 0.23; p = 0.03) and LH (r = 0.25; p = 0.02). CONCLUSIONS: Our results
      indicate a possible role of estradiol in promoting the development of atherogenic
      lipid milieu in men with CAD. Simultaneously, the observed association between
      increased FSH and LH levels with increased levels of HDL cholesterol might
      suggest a protective effect of these hormones.

PMID- 15860390
TI  - Doxazosin GITS versus standard doxazosin in mild to moderate hypertension.
AB  - BACKGROUND: The selective alpha 1-adrenoceptor antagonist doxazosin in both
      standard formulation and gastrointestinal therapeutic system (GITS) controlled
      release formulation is effective for hypertension without having a negative
      impact on serum lipids. This study was designed to compare the relative efficacy
      of these two formulations of doxazosin on clinic and ambulatory blood pressure
      and serum lipids in patients with mild to moderate hypertension. METHODS:
      Hypertensive patients aged 18-70 years (n = 335) were evaluated in a multi-center
      prospective randomized study. Following a 2-week placebo run-in phase, patients
      were randomized to receive doxazosin 2 or 4 mg, with dose titration, or doxazosin
      GITS 4 mg, no dose titration, for 9 weeks. RESULTS: Both doxazosin formulations
      reduced clinic diastolic and systolic blood pressure from baseline (P < 0.0001).
      Doxazosin GITS and doxazosin 4 mg had similar blood pressure-lowering effects.
      Doxazosin GITS reduced sitting diastolic and systolic blood pressure compared
      with doxazosin 2 mg (P < 0.01 for both). A greater proportion of the doxazosin
      GITS group reached goal blood pressure (< or = 140/90 mm Hg) after 9 weeks
      compared with the doxazosin 2-mg group. All doses of doxazosin reduced 24-h and
      daytime (7:00 am to 10:00 pm) ambulatory blood pressure from baseline (all P <
      0.01). Doxazosin GITS significantly reduced nighttime (10:00 pm to 7:00 am)
      ambulatory blood pressure from baseline. A neutral effect on serum lipids was
      observed with doxazosin. CONCLUSIONS: Doxazosin GITS and doxazosin were effective
      in reducing clinic and ambulatory blood pressure. The GITS formulation reduced
      the need for dose titration. Both doxazosin formulations were well tolerated.

PMID- 15860392
TI  - Cholesterol levels after 3 days of high-dose simvastatin in patients at moderate
      to high risk for coronary events.
AB  - BACKGROUND: Elevated levels of low-density lipoprotein cholesterol (LDL-C) impair
      vascular function by a variety of mechanisms. HMG CoA reductase inhibitors
      (statins) improve endothelial function by lowering LDL-C and possibly by other
      "pleiotropic" effects. How rapidly statins can lower LDL-C has not been
      thoroughly studied. METHODS: We examined the lipid response to 3 days of high
      dose simvastatin in a randomized prospective double-blind placebo-controlled
      crossover study. Twenty-seven subjects at moderate to high risk for coronary
      heart disease (CHD) received either simvastatin 80 mg/day for 3 days followed by
      placebo for 3 days or placebo followed by simvastatin. After a washout period of
      10 to 14 days, subjects received the opposite treatment. Nonfasting blood lipid
      levels, including total cholesterol, direct LDL-C, high-density lipoprotein
      cholesterol (HDL-C), and triglycerides, were obtained before randomization and
      after each 3-day treatment period. RESULTS: The mean LDL-C level at baseline was
      107 mg/dl and decreased 24% in patients receiving simvastatin and 5.6% in
      patients receiving placebo (P < 0.001). Statistically significant reductions were
      also achieved in the total cholesterol and cholesterol/HDL-C ratio: 14% and 12%,
      respectively. Changes in HDL-C and triglyceride levels were not significant.
      CONCLUSION: Treatment with simvastatin for only 3 days results in a 24% drop in
      the LDL-C level. As defined by ATPIII, this decrease is comparable to that
      necessary to lower the LDL-C from one risk level to a lower one and is,
      therefore, both clinically and statistically significant.

PMID- 15860393
TI  - Myocardial infarction as complication of left atrial myxoma.
AB  - Although cardiac myxomas are histologically benign, they tend to form emboli and
      cause intracardiac obstruction, so that they must be classified as potentially
      fatal tumors of the heart. The probability of arterial embolism is closely
      correlated with the morphology of the tumor. Thus, villous myxomas are more
      fragile and form emboli more often. Nuclear spin tomography and echocardiographic
      cine-mode sequences provide impressive images of the potential for embolism. It
      appears that coronary embolism may be more frequent in the group of myxoma
      patients than generally is assumed. These may present as acute myocardial
      ischemia with the typical clinical symptoms of acute myocardial infarction, as a
      silent infarct, shock, syncope or as sudden cardiac death. Besides our case
      report this paper will give an overview on published data on coronary embolism in
      patients with atrial myxoma. Interestingly there is a tendency for spontaneous
      recanalization of the obstructed coronary vessels, perhaps because of the tumors'
      tissue composition. Therefore it is reasonable to perform transoesophageal
      echocardiography to check out embolic sources like myxoma, when pathogenesis of
      myocardial infarction remains unclear after coronary angiography.

PMID- 15860394
TI  - Opposite effects of coronary artery disease and hypertrophic cardiomyopathy on
      left ventricular long axis function during dobutamine stress.
AB  - BACKGROUND: The mechanism for reduced early diastolic long axis lengthening
      velocity in hypertrophic cardiomyopathy (HCM) is not known. METHODS: We measured
      simultaneous septal long axis amplitude and early lengthening velocity in 23
      patients with HCM, 23 normal subjects and 22 patients with coronary artery
      disease (CAD) of left anterior descending artery. RESULTS: Resting amplitude and
      lengthening velocity were reduced in HCM 0.9+/-0.2 cm, 3.5+/-1.9 cm/s but equally
      in CAD 1.0+/-0.3 cm, 4.1+/-2.5 cm/s vs. 1.3+/-0.2 cm, 6.3+/-1.7 cm/s in normals,
      p < 0.01 for both vs. normal. With dobutamine stress, lengthening velocity
      increased by 2.7+/-1.9 cm/s (p < 0.001) in normals, by 2.8+/-2.5 cm/s (p < 0.001)
      in HCM but not in patients with CAD 0.5+/-2.1, p = NS. Increment in total long
      axis amplitude was subnormal in CAD and HCM. However, increment in lengthening
      velocity was higher with stress for corresponding change in amplitude in HCM
      compared with CAD (chi2) = 16.5, p < 0.001). An increase in early lengthening
      velocity by 2 cm/s was 77% sensitive and 70% specific in discriminating between
      HCM and CAD. Post-ejection shortening developed or worsened in all CAD patients
      indicating ischemia but not in any with HCM. CONCLUSIONS: Reduced peak early
      lengthening velocity is not specific for HCM but also occurs in CAD. Unlike CAD,
      lengthening velocity increases in HCM with stress and there is no aggravation of
      post-ejection shortening, suggesting that the abnormal relaxation is not due to
      subendocardial ischemia in HCM. The greater recoil velocity per unit deformation
      in HCM compared with CAD, indicates elastic mechanism with increased passive
      muscle stiffness due to fibrosis or fibre disarray.

PMID- 15860395
TI  - Post-exercise heart rate, blood pressure and oxygen uptake dynamics in pediatric
      patients with Fontan circulation Comparison with patients after right ventricular
      outflow tract reconstruction.
AB  - BACKGROUND: Post-exercise heart rate (HR) and oxygen uptake (V O(2)) recover more
      slowly in patients with the Fontan circulation, but little is known about the
      determinants of the delayed recovery. PURPOSE: To evaluate the post-exercise
      cardiovascular dynamics and clinical profiles in these patients. METHODS AND
      RESULTS: We studied 51 Fontan patients (14+/-4 years) (atriopulmonary connection,
      APC = 18 and total cavopulmonary connection, TCPC = 33) and compared the results
      with 34 patients after right ventricular outflow tract reconstruction (RVOTR)
      with identical exercise capacity and arterial baroreflex sensitivity (BRS) (15+/
      4 years) and with 26 controls (14+/-4 years). There were no differences in post
      exercise HR or VO2 declines between the Fontan and RVOTR groups. Although the
      systolic blood pressure (SBP) decline was delayed in the RVOTR group (p < 0.01),
      its early decline in the Fontan group was rapid and equivalent to that in
      controls. In Fontan patients, BRS had a great impact on early HR decline (p <
      0.05) and early VO2 decline was determined by peak VO2, age and cardiac index (p
      < 0.05-0.001). TCPC and lower BRS were the main determinants of the slower SBP
      decline (p < 0.05). In another study of repeated paired exercise tests before and
      after Fontan operation, post-exercise SBP decline became greater after the
      operation (p < 0.07). CONCLUSIONS: In the Fontan group, post-exercise HR and VO2
      declines are markedly delayed and are determined by cardiac vagal nervous
      activity, exercise capacity and age, respectively. Despite identical impaired
      hemodynamics and exercise capacity, post-exercise SBP decline is greater in the
      Fontan group, especially after APC, than in the RVOTR patients.

PMID- 15860396
TI  - Treatment of symptomatic acute internal mammary artery graft dissection by
      percutaneous stent placement.

PMID- 15860397
TI  - Effects of metronidazole on hyperlipidaemia.

PMID- 15860398
TI  - Atrioventricular conduction disturbances secondary to Lyme disease.

PMID- 15860399
TI  - Elevated plasma homocysteine level in slow coronary flow.
AB  - BACKGROUND: Slow flow velocity of dye in coronary arteries is not an infrequent
      finding during routine coronary angiography and its precise mechanism is unknown.
      In this study, we measured the plasma homocysteine level in patients with slow
      coronary flow (SCF) in comparison with subjects having normal coronary flow
      (NCF). METHOD: The study consisted 39 patients (mean age, 47+/-8 years) with
      angiographically diagnosed SCF. SCF was defined according to TIMI frame count
      (TFC) method. Thirty subjects (mean age 46+/-8 years) with NCF served as control
      group. Plasma homocysteine levels were measured after 12 h fasting period in each
      subject. RESULTS: Baseline demographic properties were similar in both groups. In
      patients with SCF, TFC was significantly higher than those with NCF. Similarly,
      in patients with SCF plasma homocysteine level was significantly higher than that
      of control group (14.1+/-2.2 vs. 5.5+/-1.3 micromol/l, respectively p < 0.001).
      CONCLUSION: Elevated plasma homocysteine level supports the hypothesis that
      endothelial function is impaired in slow coronary flow.

PMID- 15860400
TI  - Kearns-Sayre syndrome associated with trifascicular block and QT prolongation.
AB  - Patients suffering from Kearns-Sayre syndrome (KSS) often develop conduction
      defects that may lead to syncope or sudden cardiac death. The association of
      conduction abnormalities with prolonged QT interval in these patients is very
      rare. We describe a patient with KSS and diabetes mellitus who suffered a
      torsades de pointes-induced syncopal attack, in the presence of trifascicular
      block and QT prolongation (QTc: 574 ms). The patient was successfully treated
      with permanent pacing. This case highlights that torsades de pointes represents a
      potential mechanism of syncope or sudden cardiac death in patients with KSS.

PMID- 15860401
TI  - Sinus of Valsalva fistula with quadricuspid aortic valve, a first reported
      association.
AB  - Quadricuspid aortic valve and sinus of Valsalva fistula are rare congenital
      anomalies. We report the first case of association of these two congenital
      anomalies in an adult patient and the important role of Magnetic Resonance
      Imaging (MRI) in establishing and confirming the correct diagnosis and helping in
      planning the treatment.

PMID- 15860402
TI  - Angiotensin-converting enzyme inhibitors prevent LDL-induced endothelial
      dysfunction by reduction of asymmetric dimethylarginine level.

PMID- 15860403
TI  - Myocarditis with ST-Elevation Myocardial Infarction presentation in young man. A
      case series of 11 patients.
AB  - Acute myocarditis may mimic an infarction. Aim is to describe a case series of
      peculiar myocarditis. From 1997 to 2003, 11 male patients (age 17-39 years) were
      admitted with diagnosis of acute myocardial infarction, localized ST segment
      elevation and minimal enzyme release. Ten patients had fever in the 3 days prior
      to admission. Eight patients underwent coronary angiography showing normal
      coronary arteries. All remained asymptomatic at long term follow-up. In
      conclusion, myocarditis with ST elevation myocardial infarction presentation is
      an acute benign syndrome especially frequent in young males.

PMID- 15860404
TI  - A rare case of large mediastinal germ cell tumor detected by echocardiography.
AB  - We describe a rare case of a large mediastinal germ cell tumor detected by
      modified views of transthoracic echocardiography. CT scanning and histological
      findings after tumor resection confirmed diagnosis. This case demonstrates the
      clinical importance of echocardiography in diagnosis of extra-cardiac masses.

PMID- 15860405
TI  - Anuria due to acute bilateral renal vein occlusion after thrombolysis for
      pulmonary embolism.
AB  - Severe hemorrhage is the more frequent complication of thrombolysis, with
      intracranial bleeding the most critical one. We report a 73-year-old woman with
      major pulmonary embolism (PE), yet haemodynamically stable, in whom thrombolysis
      resulted in severe complications with acute renal failure (ARF) due to bilateral
      renal vein occlusion, quite unexpected; this complication has never been
      reported, as yet. We believe that disrupture of peripheral vein clots by
      thrombolysis led to migration of thrombi particles upwards to the inferior vena
      cava (IVC) and bilateral renal vein occlusion. However, the large thrombus
      straddled to the bifurcation of the main pulmonary trunk and extending to the
      right pulmonary artery, as visualized by transthoracic (TTE) and transesophageal
      echocardiogram (TEE), was not affected by thrombolysis. Finally, endogenous
      fibrinolytic activity, under low molecular weight heparin, resulted in a slow
      dissolution of the pulmonary thrombus and restoration of kidney function.

PMID- 15860406
TI  - Complex Regional Pain Syndrome type I following radial artery cardiac
      catheterization.

PMID- 15860407
TI  - Massive aortic aneurysm and dissection in repaired tetralogy of Fallot; diagnosis
      by cardiovascular magnetic resonance imaging.

PMID- 15860408
TI  - Incretin hormones and insulin sensitivity.
AB  - Incretin hormones such as glucagon-like peptide-1 (GLP-1) and the longer lasting
      analog exendin-4 show clinical promise for the treatment of diabetes because of
      glucoregulatory activities that enhance beta-cell function and growth, and
      actions in the central nervous system that induce satiety and decrease caloric
      intake. The actions of these peptides on insulin-responsive tissues is less
      clear, but recent advances indicate that chronic treatment with exendin-4
      increases insulin sensitivity via two distinct mechanisms: one is attributable to
      changes in food intake and the subsequent improvements in glycemia; the second is
      largely independent of reductions in blood glucose. In addition, exendin-4 might
      also have direct effects on beta-cell neogenesis that are independent of insulin
      demand.

PMID- 15860409
TI  - Clinical correlates of environmental endocrine disruptors.
AB  - Endocrine disrupting chemicals (EDCs), such as environmental estrogens, are
      hypothesized to be associated with a global decrease in sperm counts, other male
      reproductive tract problems and increasing rates of female breast cancer. Results
      of human population studies do not support the association between certain
      organochlorine EDCs and female breast cancer. Moreover, there is minimal evidence
      linking EDCs or exposure to other environmental chemicals with male reproductive
      tract problems. With the exception of the increasing incidence of testicular
      cancer, it is also questionable whether male reproductive tract problems are
      increasing, decreasing or unchanged. However, several studies report large
      differences in sperm count and quality and other endocrine-related problems
      within countries and regions, but the environmental, dietary and/or lifestyle
      factors responsible remain unknown.

PMID- 15860410
TI  - Origin and development of GnRH neurons.
AB  - Gonadotropin-releasing hormone (GnRH) is an essential decapeptide, with both
      endocrine and neuromodulatory functions in vertebrates. GnRH-containing cells of
      the forebrain were thought to originate in the olfactory placode and migrate to
      their central nervous system destinations, and those of the midbrain to arise
      locally from the neural tube. Here, the embryonic origins of GnRH cells are re
      examined in light of recent data suggesting that forebrain GnRH cells arise from
      the anterior pituitary placode and cranial neural crest, from where they migrate
      to their final destinations. The emerging picture suggests that GnRH cells do not
      originate from the olfactory placodes, but arise from multiple embryonic origins,
      and transiently associate with the developing olfactory system as they migrate to
      ventral forebrain locations.

PMID- 15860411
TI  - Biophysical basis of pituitary cell type-specific Ca2+ signaling-secretion
      coupling.
AB  - All secretory pituitary cells exhibit spontaneous and extracellular Ca2+
      dependent electrical activity. Somatotrophs and lactotrophs fire plateau-bursting
      action potentials, which generate Ca2+ signals of sufficient amplitude to trigger
      hormone release. Gonadotrophs also fire action potentials spontaneously, but as
      single, high-amplitude spikes with limited ability to promote Ca2+ influx and
      secretion. However, Ca2+ mobilization in gonadotrophs transforms single spiking
      into plateau-bursting-type electrical activity and triggers secretion. Patch
      clamp analysis revealed that somatotrophs and lactotrophs, but not gonadotrophs,
      express BK (big)-type Ca2+-controlled K+ channels, activation of which is closely
      associated with voltage-gated Ca2+ influx. Conversely, pituitary gonadotrophs
      express SK (small)-type Ca2+-activated K+ channels that are colocalized with
      intracellular Ca2+ release sites. Activation of both channels is crucial for
      plateau-bursting-type rhythmic electrical activity and secretion.

PMID- 15860412
TI  - Growth hormone abuse: methods of detection.
AB  - In the past two decades, growth hormone (GH) has been considered as a performance
      enhancing drug in the sport world, certainly favoured by the awareness that there
      is not yet an approved method for detecting its abuse. Because resting or random
      measurements of plasma GH concentrations per se are meaningless, new methods have
      been devised to evaluate plasma levels of GH-sensitive substances that are more
      stable, and hence detectable, than the hormone itself. This review discusses some
      of the most recently proposed approaches, including a diagnostic algorithm, based
      on the timed application of different tests, which, collectively, would have a
      high diagnostic capability.

PMID- 15860413
TI  - Multiple functions of type 10 17beta-hydroxysteroid dehydrogenase.
AB  - Human 17beta-hydroxysteroid dehydrogenase type 10 (17beta-HSD10) is a
      mitochondrial enzyme encoded by the SCHAD gene, which escapes chromosome X
      inactivation. 17Beta-HSD10/SCHAD mutations cause a spectrum of clinical
      conditions, from mild mental retardation to progressive infantile
      neurodegeneration. 17Beta-HSD10/SCHAD is essential for the metabolism of
      isoleucine and branched-chain fatty acids. It can inactivate 17beta-estradiol and
      steroid modulators of GABA(A) receptors, and convert 5alpha-androstanediol into
      5alpha-dihydrotestosterone (DHT). Certain malignant prostatic epithelial cells
      contain high levels of 17beta-HSD10, generating 5alpha-DHT in the absence of
      testosterone. 17Beta-HSD10 has an affinity for amyloid-beta peptide, and might be
      linked to the mitochondrial dysfunction seen in Alzheimer's disease. This
      versatile enzyme might provide a new drug target for neuronal excitability
      control and for intervention in Alzheimer's disease and certain cancers.

PMID- 15860414
TI  - Thyroid hormone receptor mutations and disease: beyond thyroid hormone
      resistance.
AB  - Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that
      mediate the biological activities of thyroid hormone (T3). Two THR genes (A and
      B), located on different chromosomes, yield four T3-binding isoforms with highly
      conserved sequences in the DNA- and ligand-binding domains. Mutations of THRB
      cause a human genetic disease, thyroid hormone resistance syndrome (RTH).
      Comprehensive genomic profiling unveiled the contribution of novel change-of
      function mutations of TRbeta to the pathogenesis of RTH. In addition,
      abnormalities associated with mutations of the THRA gene have been uncovered
      recently. The phenotypic manifestations of mutated THRB and THRA genes are
      distinct, indicating isoform-dependent actions of TR mutants in vivo. Therefore,
      mutant TRs provide a new paradigm to understand the molecular basis of receptor
      disease.

PMID- 15860415
TI  - FoxO proteins in insulin action and metabolism.
AB  - There is increasing evidence that Forkhead box 'Other' (FoxO) proteins, a
      subgroup of the Forkhead transcription factor family, have an important role in
      mediating the effects of insulin and growth factors on diverse physiological
      functions, including cell proliferation, apoptosis and metabolism. Genetic
      studies in Caenorhabditis (Caenorhabditis elegans) and Drosophila demonstrate
      that FoxO proteins are ancient targets of insulin-like signaling involved in the
      regulation of metabolism and longevity. Studies in mammalian cells reveal that
      FoxO proteins regulate cell cycle progression and promote resistance to oxidative
      stress; both in vivo and cell culture studies support the concept that FoxO
      proteins have an important role in mediating the effects of insulin on
      metabolism, including its effects on hepatic glucose production. Phosphorylation
      and acetylation modulate FoxO function and control nuclear-cytoplasmic shuttling,
      DNA binding and protein-protein interactions. FoxO transcription factors exert
      positive and negative effects on gene expression, through direct binding to DNA
      target sites and protein-protein interactions with other transcription factors
      and coactivators. This paper provides an overview of studies leading to the
      identification of FoxO proteins as targets of insulin action and the mechanisms
      mediating the effects of insulin-like signaling on FoxO function, emphasizing the
      role of FoxO proteins in mediating the effects of insulin on metabolism.

PMID- 15860416
TI  - Insulin-like growth factor-I treatment of growth disorders, diabetes mellitus and
      insulin resistance.
AB  - Insulin-like growth factor I (IGF-I) has many potential therapeutic uses because
      of its varied effects--growth promotion, insulin-like influence on glucose
      metabolism, and neuroprotection resulting from cell-proliferative and
      antiapoptotic properties--but they have not been investigated systematically in
      clinical situations. The growth-promoting effect of recombinant human IGF-I
      (rhIGF-I) in the extensively studied growth hormone insensitivity syndrome (GHIS;
      Laron syndrome) signifies an endocrine role for the GH-IGF system. The metabolism
      of (adult) patients with severe insulin resistance is improved by rhIGF-I, which-
      together with insulin therapy--also improves metabolic control in type 1 and 2
      diabetes. Further studies on IGF-I metabolic effects and growing understanding of
      the IGF-I-IGF-binding protein system could open new therapeutic avenues.

PMID- 15860418
TI  - The use of genetics to dissect plant secondary pathways.
AB  - Plant secondary metabolism comprises an enormous diversity in compounds and
      enzymes, and wide spectra of mechanisms of gene regulation and of transport of
      metabolites and enzymes. Genetic approaches using the model plant Arabidopsis
      thaliana have contributed importantly to recent progress in understanding
      glucosinolate biosynthesis and its intricate linkage with auxin homeostasis.
      Arabidopsis genetics have also caused revolutionary changes in the existing views
      on the metabolic intermediates and enzyme activities that are involved in
      phenylpropanoid biosynthesis. Some progress has been achieved in understanding
      the transcriptional regulation of the flavonoid pathway. Transcriptional
      regulators have also been identified for glucosinolate and terpenoid indole
      alkaloid biosynthesis.

PMID- 15860419
TI  - Single-cell genomics.
AB  - The evolution of higher plants depended on the ability of cells to express
      hereditary information in many different ways and led to the development of
      specialized cell types, reflecting an elaborate system of control over gene
      expression in the individual component cells of various tissues. Bulk tissue
      sampling results in the loss of spatial resolution, and recent efforts have been
      directed toward improving access to specialized cell types in plants. Access to
      the contents of individual cells followed by analyses using post-genomic
      technologies promise to revolutionize our understanding of the differentiation of
      specialized cell types, and to enable downstream applications aimed at harnessing
      their unique biochemical properties.

PMID- 15860420
TI  - Metabolomics, genomics, proteomics, and the identification of enzymes and their
      substrates and products.
AB  - A large proportion of the genes in any plant genome encode enzymes of primary and
      specialized (secondary) metabolism. Not all plant primary metabolites, those that
      are found in all or most species, have been identified. Moreover, only a small
      portion of the estimated hundreds of thousand specialized metabolites, those
      found only in restricted lineages, have been studied in any species. The
      correlative analysis of extensive metabolic profiling and gene expression
      profiling has proven a powerful approach for the identification of candidate
      genes and enzymes, particularly those in secondary metabolism. The final
      characterization of substrates, enzymatic activities, and products requires
      biochemical analysis, which has been most successful when candidate proteins have
      homology to other enzymes of known function. The challenges are to identify new
      types of enzymes and to develop biochemical techniques that are suitable for
      large-scale analysis.

PMID- 15860421
TI  - Structure-function relationships in plant phenylpropanoid biosynthesis.
AB  - Plants, as sessile organisms, evolve and exploit metabolic systems to create a
      rich repertoire of complex natural products that hold adaptive significance for
      their survival in challenging ecological niches on earth. As an experimental tool
      set, structural biology provides a high-resolution means to uncover detailed
      information about the structure-function relationships of metabolic enzymes at
      the atomic level. Together with genomic and biochemical approaches and an
      appreciation of molecular evolution, structural enzymology holds great promise
      for addressing a number of questions relating to secondary or, more
      appropriately, specialized metabolism. Why is secondary metabolism so adaptable?
      How are reactivity, regio-chemistry and stereo-chemistry steered during the multi
      step conversion of substrates into products? What are the vestigial structural
      and mechanistic traits that remain in biosynthetic enzymes during the
      diversification of substrate and product selectivity? What does the catalytic
      landscape look like as an enzyme family traverses all possible lineages en route
      to the acquisition of new substrate and/or product specificities? And how can one
      rationally engineer biosynthesis using the unique perspectives of evolution and
      structural biology to create novel chemicals for human use?

PMID- 15860422
TI  - Glycosyltransferases: managers of small molecules.
AB  - Studies of the glycosyltransferases (GTs) of small molecules have greatly
      increased in recent years as new approaches have been used to identify their
      genes and characterize their catalytic activities. These enzymes recognize
      diverse acceptors, including plant metabolites, phytotoxins and xenobiotics.
      Glycosylation alters the hydrophilicity of the acceptors, their stability and
      chemical properties, their subcellular localisation and often their bioactivity.
      Considerable progress has been made in understanding the role of GTs in the plant
      and the utility of GTs as biocatalysts, the latter arising from their regio- and
      enantioselectivity and their ability to recognize substrates that are not limited
      to plant metabolites.

PMID- 15860423
TI  - The glucosinolate-myrosinase system in an ecological and evolutionary context.
AB  - Functional analysis of natural variation in the model species Arabidopsis
      thaliana has enabled the cloning of many glucosinolate biosynthesis and
      hydrolysis genes. Variation in these genes is central to understanding the
      ecological role of the glucosinolate-myrosinase defense system, and allows us to
      dissect the evolutionary and ecological forces that shape polymorphism at
      underlying loci. These same genes are also variable in other crucifer species,
      suggesting the presence of recurring selection, possibly mediated by insects. By
      utilizing the genomic tools available in A. thaliana to investigate these loci
      fully, it might be possible to generate detailed evolutionary or ecological
      models to apply to other species.

PMID- 15860424
TI  - Transcriptional control of flavonoid biosynthesis: a complex network of conserved
      regulators involved in multiple aspects of differentiation in Arabidopsis.
AB  - Secondary metabolism is not only a protective mechanism against biotic and
      abiotic stresses but also part of the molecular programs that contribute to
      normal plant growth and development. In this context, secondary metabolism is
      intimately linked with other aspects of plant differentiation in which
      transcription factors play a key coordinating role. Recent findings illustrate
      the complexity of regulatory networks that control flavonoid biosynthesis in
      Arabidopsis and other species. They also underline the close relationship between
      secondary metabolism and epidermal and seed differentiation in Arabidopsis, and
      the central role played by conserved WD40 domain proteins in regulating these
      processes. This review highlights recent advances in this field and describes how
      they help our understanding of the molecular regulation of plant secondary
      metabolism.

PMID- 15860425
TI  - Metabolon formation and metabolic channeling in the biosynthesis of plant natural
      products.
AB  - Metabolon formation and metabolic channeling in plant secondary metabolism enable
      plants to effectively synthesize specific natural products and to avoid metabolic
      interference. Channeling can involve different cell types, take advantage of
      compartmentalization within the same cell or proceed directly within a metabolon.
      New experimental approaches document the importance of channeling in the
      synthesis of isoprenoids, alkaloids, phenylpropanoids, flavonoids and cyanogenic
      glucosides. Metabolon formation and metabolic channeling in natural-product
      synthesis facilitate attempts to genetically engineer new pathways into plants to
      improve their content of valuable natural products. They also offer the
      opportunity to introduce new traits by genetic engineering to produce plant
      cultivars that adhere to the principle of substantial equivalence.

PMID- 15860426
TI  - A role for intra- and intercellular translocation in natural product
      biosynthesis.
AB  - The formation and storage of plant natural products such as phenylpropanoids,
      terpenoids and alkaloids are dynamic and complex processes that involve multiple
      subcellular compartments and cell types. Evidence is emerging to show that
      consecutive enzymes of phenylpropanoid and flavonoid biosynthesis are organized
      into macromolecular complexes that can be associated with endomembranes, that
      monoterpenoid biosynthetic enzymes are exclusively localized to highly
      specialized glandular trichome secretory cells and that complex monoterpenoid
      indole- and morphinan alkaloids require a combination of phloem parenchyma,
      laticifers and epidermal cells for their synthesis and storage. Highly ordered,
      protein-mediated processes that involve intra- and intercellular translocation
      need be considered when attempting to understand how a plant can regulate the
      formation and accumulation of complex but well-defined natural product profiles.

PMID- 15860427
TI  - Transporters of secondary metabolites.
AB  - The membrane transport of plant secondary metabolites is a newly developing
      research area. Recent progress in genome and expressed sequence tag (EST)
      databases has revealed that many transporters and channels exist in plant genome.
      Studies of the genetic sequences that encode these proteins, and of phenotypes
      caused by the mutation of these sequences, have been used to characterize the
      membrane transport of plant secondary metabolites. Such studies have clarified
      that membrane transport is fairly specific and highly regulated for each
      secondary metabolite. Not only genes that are involved in the biosynthesis of
      secondary metabolites but also genes that are involved in their transport will be
      important for systematic metabolic engineering aimed at increasing the
      productivity of valuable secondary metabolites in planta.

PMID- 15860428
TI  - The secondary metabolism of Arabidopsis thaliana: growing like a weed.
AB  - Despite its small stature, short life-cycle and highly reduced genome,
      Arabidopsis thaliana has a complement of secondary metabolites that is every bit
      as numerous and diverse as those of other plant taxa. The list of secondary
      metabolites isolated from this model species has expanded more than five-fold in
      the past ten years, and many more substances are likely to be added in the near
      future. Among the classes of compounds recently discovered are coumarins,
      benzenoids and terpenoids. Many A. thaliana secondary metabolites appear to have
      internal roles within the plant instead of (or in addition to) mediating
      ecological interactions.

PMID- 15860429
TI  - Flavonoids as developmental regulators.
AB  - Flavonoids, usually regarded as dispensable phytochemicals derived from plant
      secondary metabolism, play important roles in the biology of plants by affecting
      several developmental processes. Bioactive flavonoids also signal to microbes,
      serve as allelochemicals and are important nutraceuticals in the animal diet.
      Despite the significant progress made in identifying flavonoid pathway genes and
      regulators, little is currently known about the protein targets of flavonoids in
      plant or animal cells. Recently, there have been advances in our understanding of
      the roles that flavonoids play in developmental processes of plants. The multiple
      cellular roles of flavonoids can reflect their chemical diversity, or might
      suggest the existence of cellular targets shared between many of these seemingly
      disparate processes.

PMID- 15860430
TI  - Current progress in the use of traditional medicines and nutraceuticals.
AB  - Traditional medicines in the form of botanical dietary supplements and
      nutraceuticals have found a place in 21st century healthcare. They nonetheless
      all contain compounds that are foreign to humans (i.e. xenobiotics) and that are
      subject to the same pharmacological issues encountered by synthetic therapeutic
      agents. It is crucial therefore for all parties, the medical profession,
      investigative scientists, the regulatory agencies and the public, to understand
      the particular characteristics of botanicals and nutraceuticals and their
      potential for success and failure in preventing and confronting disease.

PMID- 15860431
TI  - Engineering of plant natural product pathways.
AB  - Although many important and valuable traits are associated with plant natural
      products, engineering natural product pathways for plant improvement has often
      been limited by a lack of understanding of their biochemistry, and by the need
      for coordinate regulation of multiple gene activities. New approaches are
      facilitating both the discovery of genes that encode natural products and pathway
      engineering. Notable successes have been reported in altering complex pathways to
      improve plant quality and resistance to biotic and abiotic stresses.

PMID- 15860432
TI  - Need for multidisciplinary research towards a second green revolution.
AB  - Despite recent achievements in conventional plant breeding and genomics, the rate
      of increase of crop yields is declining and thus there is a need for a second
      green revolution. Advances within single disciplines, alone, cannot solve the
      challenges of increasing yield. As scientific disciplines have become
      increasingly diversified, a more complete understanding of the mechanisms by
      which genetic and environmental variation modify grain yield and composition is
      needed, so that specific quantitative and quality targets can be identified. To
      achieve this aim, the expertise of plant genomics, physiology and agronomy, as
      well as recently developed plant modelling techniques, must be combined. There
      has been recent progress in these individual disciplines, but multidisciplinary
      approaches must be implemented to tackle drought stress and salinity as major
      constraints to achieving sufficient grain yield in the future.

PMID- 15860433
TI  - Dietary lignans: potential role in cancer prevention.
AB  - Recent in vitro, animal, and epidemiological studies suggest that dietary lignans
      may be chemopreventive, potentially through anti-estrogenic, anti-angiogenic, pro
      apoptotic, and anti-oxidant mechanisms. In this article, we review lignan food
      sources and metabolism, proposed anti-carcinogenic mechanisms, and the evidence
      for a role of lignans in breast, colon, and prostate cancer prevention from
      animal and epidemiologic literature. Although a number of in vitro and animal
      studies support a role for lignan-rich foods and purified lignans in the
      modulation of cancer events of the breast, prostate, and colon, epidemiological
      studies, sparse and often retrospective in nature, offer inconsistent findings.
      The most support for a role of lignans in cancer is observed for premenopausal
      breast cancer. Additional epidemiological studies that use a prospective design
      and well-developed food databases and questionnaires are needed to adequately
      evaluate the role of lignans in cancer prevention.

PMID- 15860434
TI  - Dietary patterns and risk of cancer of the oral cavity and pharynx in Uruguay.
AB  - From 1995 to 2002, a case-control study on food groups and risk of cancer of the
      oral cavity and pharynx was conducted in Montevideo, Uruguay. Two hundred thirty
      cases were frequency-matched to 460 controls on age, residence, and urban/rural
      status. The study was restricted to men. The relationship between foods and risk
      of oral and pharyngeal squamous cell carcinoma was examined through: 1)
      individual food group analysis, 2) factor analysis, and 3) determination of
      empirical scores. The results were similar. Factor analysis generated 2 patterns,
      which were labeled as "stew" and "vegetables and fruits." The stew pattern loaded
      positively on boiled meat, cooked vegetables, potato, and sweet potato. This
      pattern was directly associated with risk of oral and pharyngeal cancer [odds
      ratio (OR), 3.75; 95% confidence interval (CI), 1.99-7.06; P value for
      trend=0.0002]. The vegetables and fruits factor loaded positively on raw
      vegetables, citrus fruits, other fruits, liver, fish, and desserts. This pattern
      was inversely associated with risk of oropharyngeal carcinoma (OR, 0.34; 95% CI,
      0.18-0.64; P value for trend=0.0008). Joint effects of high intake of risk foods
      and low intake of protective foods were associated with a risk of 12.0 (95% CI,
      4.1-34.6). Our study confirms the important role of dietary factors in oral and
      pharyngeal cancer risk and suggests that the analysis of dietary patterns is a
      powerful tool to investigate the links between nutrition and cancer.

PMID- 15860435
TI  - Does physical activity modify the association between body mass index and
      colorectal adenomas?
AB  - Although both physical inactivity and obesity have been associated with an
      increased risk of colorectal adenomas, it is unclear whether physical activity
      modifies the relationship between obesity and colorectal adenomas or through what
      mechanism this might occur. The aim of this study is to evaluate whether physical
      activity modifies the relationship between body mass index (BMI) and colorectal
      adenomas and whether apoptosis is a plausible mechanism responsible for this
      effect modification. Study subjects were part of a large, cross-sectional study,
      the Diet and Health Study III. Consecutive patients underwent colonoscopy between
      August 1998 and March 2000. Apoptosis was measured by morphological evaluation of
      hematoxylin and eosin-stained sections obtained from rectal pinch biopsy samples.
      There were 226 patients with adenomas and 494 adenoma-free controls. When
      comparing overweight subjects with the referent group (high physical
      activity/normal BMI), the relative odds of having an adenoma decreased as
      physical activity increased: low (odds ratio, OR=1.6; 95% confidence interval,
      CI=0.7-3.4); moderate (OR=1.1; 95% CI=0.6-2.0); and high (OR=0.8; 95% CI=0.4
      1.6). When comparing obese subjects with the referent group, relative odds of
      having an adenoma were increased regardless of physical activity level. Apoptosis
      was not associated with obesity or physical activity. Our results suggest that
      physical activity may modify the association between obesity and colorectal
      adenoma until a high level of obesity is achieved. Apoptosis does not appear to
      be associated with obesity or physical activity.

PMID- 15860436
TI  - Diet and biomarkers of oxidative damage in women previously treated for breast
      cancer.
AB  - This study sought to evaluate the relationship between dietary intake of fat,
      polyunsaturated fat, saturated fat, arachidonic acid, and selected dietary
      antioxidants and levels of oxidative damage as measured by urinary levels of 8
      hydroxy-2'-deoxyguanosine (8-OHdG) and 8-epi-prostaglandin F2alpha (8-iso
      PGF2alpha) in women previously treated for breast cancer. Two hundred two study
      subjects participating in the Women's Healthy Eating and Living (WHEL) study were
      included in this ancillary study. Dietary intakes and concentrations of urinary 8
      OHdG and 8-iso-PGF2alpha were measured at baseline and 12 mo in the 179 women
      included in the analytical cohort. Study subjects demonstrated a significant
      reduction in dietary total, polyunsaturated, and saturated fat intake and a
      significant increase in vitamins E and C and beta-carotene intake from baseline
      to 12 mo. Linear mixed-models analysis using baseline and Year 1 data indicated
      that vitamin E intake was inversely associated with both 8-OHdG and 8-iso
      PGF2alpha. 8-Iso-PGF2alpha is increased with increased body mass index (BMI) and
      polyunsaturated fatty acid (PUFA) intake, indicating an increase in lipid
      peroxidation with greater BMI and higher PUFA intake. 8-OHdG was inversely
      related to age but positively related to arachidonic acid, indicating an increase
      in DNA damage with higher intake of arachidonic acid (meat). The results of this
      nested case-controlled study provide potential mechanisms by which a high fruit
      and vegetable, low-fat diet might reduce the recurrence rate of or early-stage
      breast cancer.

PMID- 15860437
TI  - PPARgamma, energy balance, and associations with colon and rectal cancer.
AB  - Peroxisome proliferator-activated receptor-gamma (PPARgamma) has been
      hypothesized as being involved in colorectal cancer given its role in adipocyte
      development and insulin resistance. In this study we evaluated the association
      between the Pro12Ala (P12A) PPARgamma polymorphism and body mass index (BMI),
      waist-to-hip ratio (WHR), physical activity level, and energy intake and risk of
      colorectal cancer using data from a population-based, case-control study of colon
      cancer (1,577 cases and 1,971 controls) and rectal cancer (794 cases and 1,001
      controls). We further evaluated how the P12A PPARgamma polymorphism is associated
      with obesity and fat pattern in the control population. The odd ratio for
      PPARgamma PA or AA genotype relative to the PP genotype for colon cancer was 0.9
      (95% confidence interval, CI=0.8-1.0) and for rectal cancer was 1.2 (95% CI=1.0
      1.5) adjusting for race, age, and sex. P12A PPARgamma did not significantly
      interact with BMI, WHR, energy intake, and energy expenditure to alter risk of
      colon or rectal cancer. Furthermore, the P12A PPARgamma polymorphism was not
      associated with obesity or WHR in the control population; it did not interact
      with energy intake or energy expenditure to alter risk of obesity or large WHR.
      These data do not support the hypothesis that the P12A PPARgamma polymorphism is
      associated with colon or rectal cancer through regulation of energy balance.

PMID- 15860438
TI  - Effect of dietary intake of phytoestrogens on estrogen receptor status in
      premenopausal women with breast cancer.
AB  - Although many dietary studies have focused on breast cancer risk, few have
      examined dietary influence on tumor characteristics such as estrogen receptor
      (ER) status. Because phytoestrogens may modulate hormone levels and ER
      expression, we analyzed ER status and phytoestrogen intake in a case-case study
      of 124 premenopausal breast cancer patients. We assessed intake with a food
      frequency questionnaire and obtained ER status from medical records. Rather than
      focusing on risk, we evaluated whether low intakes were more strongly associated
      with ER-negative tumors than with ER-positive disease. In logistic regression
      adjusting for potential confounders, threefold greater risks of ER-negative
      tumors relative to ER-positive tumors were associated with low intake of the
      isoflavones genistein (odds ratio, OR=3.50; 95% confidence interval, CI=1.43
      8.58) and daidzein (OR=3.10; 95% CI=1.31-7.30). Low intake of the flavonoid
      kaempferol (OR=0.36; 95% CI=0.16-0.83), the trace element boron (OR=0.33; 95%
      CI=0.13-0.83), and the phytosterol beta-sitosterol (OR=0.42; 95% CI=0.18-0.98)
      were associated with decreased risk of ER-negative tumors relative to ER-positive
      disease. Other phytoestrogens were not significantly associated with ER status.
      Thus, in premenopausal patients, some phytoestrogens may affect breast
      carcinogenesis by influencing ER status. Such findings suggest new directions for
      mechanistic research on dietary factors in breast carcinogenesis that may have
      relevance for prevention and clinical treatment.

PMID- 15860439
TI  - Increased risk of colorectal cancer due to interactions between meat consumption
      and the CD36 gene A52C polymorphism among Japanese.
AB  - A previous study showed expression of CD36, recently reported to play important
      roles in metabolism of oxidized low-density lipoprotein and long-chain fatty
      acids and to be positively correlated with colon cancer prognosis. To examine
      relationships between colorectal cancer and the CD36 gene A52C polymorphism
      according to meat consumption as a surrogate for saturated fatty acid intake, we
      conducted the present hospital-based, case-control study of 128 cases and 238 non
      cancer controls. Consumption of meat and vegetables/fruit was divided into three
      (low, moderate, and high) and two (low and high) groups, respectively. Regarding
      the risk of colorectal cancer on cross-classifying subjects for the CD36 genotype
      and meat consumption, the odds ratio (OR) for the C/C genotype with moderate meat
      consumption relative to the A/A genotype with low meat consumption was 8.30 (95%
      confidence interval, CI=2.15-32.00). None of individuals with the C/C genotype
      was in the high meat consumption group. In the low vegetables/fruit consumption
      group, the OR for the C/C genotype relative to the A/A genotype was 3.03 (95%
      CI=1.12-7.90). Our findings suggest that interactions between moderate-high meat
      consumption and the CD36 gene A52C polymorphism may increase the risk of
      colorectal cancer.

PMID- 15860440
TI  - Alpha-tocopherol suppresses mammary tumor sensitivity to anthracyclines in fish
      oil-fed rats.
AB  - Polyunsaturated fatty acids (PUFAs) have been reported to enhance the efficacy of
      chemotherapeutic agents that produce reactive oxygen species such as
      anthracyclines. We previously reported in a human breast cancer cell line that
      the increased cytotoxic activity of anthracyclines by several PUFAs was abolished
      by antioxidants and enhanced by pro-oxidants, suggesting that lipid peroxidation
      was involved in this effect. To determine the relevance of this observation in
      vivo, we examined the effect of the oxidative status of the diet on the activity
      of epirubicin against N-methylnitrosourea-induced mammary tumors in Sprague
      Dawley rats. Three groups of rats were fed a basal diet enriched with dietary n-3
      PUFA (sardine oil, 15%) alone (control group), with addition of an antioxidant
      (alpha-tocopherol, 100 UI/kg diet), or with addition of an oxidant system
      (dehydroascorbate/naphthoquinone). When the first mammary tumor reached 1 cm2,
      epirubicin was administrated weekly for 3 wk, and subsequent change in tumor size
      was documented over time. Two weeks after the end of epirubicin injections, tumor
      size was increased by 34% in the control group. In the pro-oxidant group, tumor
      size was decreased by 50%. In contrast, tumor size was increased by 188% in the
      antioxidant group. Thus, addition of pro-oxidants in a fish oil-enriched diet
      increased the sensitization of mammary tumors to chemotherapy, whereas addition
      of alpha-tocopherol suppressed tumor response in vivo, indicating that
      interaction between components of the diet has to be carefully controlled during
      chemotherapy.

PMID- 15860441
TI  - Vanadium, a versatile biochemical effector in chemical rat mammary
      carcinogenesis.
AB  - Recent studies indicate the role of the micronutrient vanadium in chemoprevention
      in many animal models, human cancer cell lines, and also in xenografted human
      carcinomas of the lung, breast, and gastrointestinal tract. The present studies
      were undertaken to ascertain the antineoplastic potential of vanadium in a
      defined model of mammary carcinogenesis. Female Sprague-Dawley rats, at 50 days
      of age, were treated with 7,12-dimethylbenz(alpha) anthracene (DMBA) (0.5 mg/100
      g body weight) by a tail vein injection in oil emulsion. Vanadium (ammonium
      metavanadate) at a concentration of 0.5 ppm (4.27 micromol/l) was supplemented in
      drinking water and given ad libitum to the experimental group after the
      carcinogen treatment, and it continued until the termination of the study. In
      vivo studies of DNA chain breaks demonstrated that vanadium offered significant
      (61%, P<0.005) protection against generation of single-strand breaks when
      compared with the DMBA control group. Supplementation of vanadium normalizes the
      level of zinc, iron, and copper as revealed by proton-induced X-ray emission
      analysis to a substantial extent (P<0.01). In vitro study of chromosomal
      aberrations (CAs) revealed that vanadium triggered a protective effect (62.9%) on
      induction of CAs, which was maximum on structural aberrations followed by
      numerical and physiological types. Histopathological and morphological analyses
      were done as end-point biomarkers. We conclude herein that vanadium has the
      potential to reduce genomic instability in mammary carcinoma in rats.

PMID- 15860442
TI  - Prevention of rat hepatocarcinogenesis by acyclic retinoid is accompanied by
      reduction in emergence of both TGF-alpha-expressing oval-like cells and activated
      hepatic stellate cells.
AB  - We investigated the preventive effects of a synthetic acyclic retinoid, NIK-333,
      on the early and late events of hepatocarcinogenesis in male F344 rats treated
      with 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). NIK-333 was administered
      once a day on consecutive days at a dose of 10, 40, or 80 mg/kg body weight along
      with the supplementation with 3'-MeDAB-containing diet for 16 wk. Animals from
      each group were sacrificed at 4 and 16 wk after the commencement of the
      experiment to determine the effect of NIK-333 on the early and late stages of
      carcinogenesis, respectively. NIK-333 suppressed the emergence of both oval-like
      cells expressing transforming growth factor (TGF)-alpha, putative progenitors of
      hepatocellular carcinoma (HCC), and activated hepatic stellate cells, major
      matrix-producing cells of the liver, in the early stage and inhibited the
      incidence of HCC in the late phase. These results suggest that NIK-333 is a
      promising drug for the chemoprevention of HCC by uniquely suppressing the early
      events of hepatocarcinogenesis, that is, development of both oval-like cells and
      fibrogenesis.

PMID- 15860443
TI  - Inhibition of the growth of premalignant and malignant human oral cell lines by
      extracts and components of black raspberries.
AB  - Black raspberries are a rich natural source of chemopreventive phytochemicals.
      Recent studies have shown that freeze-dried black raspberries inhibit the
      development of oral, esophageal, and colon cancer in rodents, and extracts of
      black raspberries inhibit benzo(a)pyrene-induced cell transformation of hamster
      embryo fibroblasts. However, the molecular mechanisms and the active components
      responsible for black raspberry chemoprevention are unclear. In this study, we
      found that 2 major chemopreventive components of black raspberries, ferulic acid
      and beta-sitosterol, and a fraction eluted with ethanol (RO-ET) during silica
      column chromatography of the organic extract of freeze-dried black raspberries
      inhibit the growth of premalignant and malignant but not normal human oral
      epithelial cell lines. Another fraction eluted with CH2Cl2/ethanol (DM:ET) and
      ellagic acid inhibited the growth of normal as well as premalignant and malignant
      human oral cell lines. We investigated the molecular mechanisms by which ferulic
      acid and beta-sitosterol and the RO-ET fraction selectively inhibited the growth
      of premalignant and malignant oral cells using flow cytometry and Western
      blotting of cell cycle regulatory proteins. There was no discernable change in
      the cell cycle distribution following treatment of cells with the RO-ET fraction.
      Premalignant and malignant cells redistributed to the G2/M phase of the cell
      cycle following incubation with ferulic acid. beta-sitosterol treated
      premalignant and malignant cells accumulated in the G0/G1 and G2/M phases,
      respectively. The RO-ET fraction reduced the levels of cyclin A and cell division
      cycle gene 2 (cdc2) in premalignant cells and cyclin B1, cyclin D1, and cdc2 in
      the malignant cell lines. This fraction also elevated the levels of p21waf1/cip1
      in the malignant cell line. Ferulic acid treatment led to increased levels of
      cyclin B1 and cdc2 in both cell lines, and p21waf1/cip1 was induced in the
      malignant cell line. beta-sitosterol reduced the levels of cyclin B1 and cdc2
      while increasing p21waf1/cip1 in both the premalignant and malignant cell lines.
      These results show for the first time that the growth inhibitory effects of black
      raspberries on premalignant and malignant human oral cells may reside in specific
      components that target aberrant signaling pathways regulating cell cycle
      progression.

PMID- 15860444
TI  - Beta-sitosterol from psyllium seed husk (Plantago ovata Forsk) restores gap
      junctional intercellular communication in Ha-ras transfected rat liver cells.
AB  - We purified compounds from the husks of psyllium seeds (Plantago ovata Forsk;
      desert Indian wheat), beginning with an ethanol extraction then followed by HP-20
      and silica gel chromatography, which restored gap junctional intercellular
      communication (GJIC) in v-Ha-ras transfected rat liver epithelial WB-F344 cell
      line (WB-Ha-ras). GJIC was assessed by a scrape loading dye transfer assay. The
      active compound was identified as beta-sitosterol based on gas chromatography
      retention times and electron ionization mass spectroscopy (EI-MS) spectrum of
      authentic beta-sitosterol. Authentic beta-sitosterol restored GJIC in the
      tumorigenic WB-Ha-ras GJIC-deficient cells at a dose of 2.4 microM. In addition,
      a similar phytosterol, stigmasterol, also restored GJIC, albeit at a lower
      activity. beta-sitosterol and stigmasterol increased the level of connexin43
      protein (Cx43) and restored phosphorylation of Cx43 to levels similar to the
      parental nontransfected cell line. We concluded that the restoration of
      intercellular communication in the GJIC-deficient, tumorigenic WB-Ha-ras cell
      line by the ethanol soluble fraction of psyllium seed husks is largely due to the
      presence of the phytosterol, beta-sitosterol. We discuss implications for dietary
      modulation of cancer by beta-sitosterol.

PMID- 15860446
TI  - Skin ulcers in lower extremities: the epidemiology and management in China.

PMID- 15860447
TI  - Wound healing research: a perspective from India.

PMID- 15860445
TI  - The microarray expression analysis identifies BAX as a mediator of beta-carotene
      effects on apoptosis.
AB  - Beta-carotene is a ubiquitous compound rich in foods. However, there are
      conflicting reports regarding its role in carcinogenesis. We performed a
      microarray expression analysis in normal [human umbilical vein endothelial cells
      (HUVECs)] and neoplastic (melanoma A375 and myelomonocytic leukemia U937)
      actively proliferating cells and found evidence that beta-carotene stimulated
      vital cellular functions in the former and suppressed them in the latter. These
      differential effects correlated with the expression of the proapoptotic BCL2
      associated X protein (BAX), which was downregulated in HUVECs and upregulated in
      the two neoplastic cell lines. The quantitative expression analysis using real
      time polymerase chain reaction largely confirmed the inhibition of B-cell
      CLL/lymphoma 2 (BCL2) pathway-mediated apoptosis in HUVECs and its activation in
      melanoma and leukemic cells. The assays for apoptosis, detecting DNA breaks and
      caspase activation, showed consistent proapoptotic and antiapoptotic effects in
      U937 and HUVEC lines, respectively. However, beta-carotene-induced expression
      changes of BAX and other BCL2 pathway genes did not lead to the predicted
      induction of apoptosis in the A375 cells.

PMID- 15860448
TI  - Fibroblast phenotypes and their relevance for wound healing.

PMID- 15860449
TI  - The role of nutrition in the management of lower extremity wounds.
AB  - From 3000 BC, healers have understood the importance of nutrition in wound care
      and used nutritional supplements to aid healing. Many of the teachings from
      Hippocrates, the father of modern-day medicine, clearly state his firm belief
      that good health can be achieved through nutrition. In the early 1900s when
      advances in biochemistry were frequent, many of the essential constituents of
      nutrition were characterized, which formed the basis for many animal and human
      wound-healing experiments. This led to the discovery of vitamin C, zinc, and many
      other components essential for the orderly progression of healing. Modern-day
      research has concentrated on finding nutritional components that can enhance
      healing through supra-physiological doses, such as in the use of the amino acids
      arginine and carnitine. However, clinicians need to be aware that approximately
      50% of patients admitted to the hospital are malnourished, requiring dietary
      supplementation; appropriate nutritional assessment and advice therefore should
      be an integral part of all wound management. This review provides an up-to-date
      commentary on the role of nutrition in wound care, with specific emphasis on
      lower limb wounds, from a historical perspective, and within it both the
      biomedical approach and current herbalist practices are considered.

PMID- 15860450
TI  - Electrical stimulation for wound healing: a review of evidence from in vitro
      studies, animal experiments, and clinical trials.
AB  - This article reviews theories linked to endogenous bioelectric currents and the
      role they may play in wound repair with further appraisal of in vitro and in vivo
      research related to the effects of clinically applicable electrical currents on
      protein synthesis, cell migration, and antibacterial outcomes. In addition,
      studies on the effects of electrical stimulation (ES) on skin grafts, donor
      sites, and musculocutaneous flaps in animals are evaluated, as well as
      assessments of numerous clinical reports that examined the effects of ES on
      angiogenesis, perfusion, PtcO2, and epithelialization. Finally, a plethora of
      clinical trials related to the responses of chronic lower extremity wounds to ES
      therapy are reviewed, with emphasis on wounds caused by venous insufficiency,
      diabetic neuropathy, and ischemia in patients with and without diabetes mellitus.
      A glossary that addresses ES terminology is also included.

PMID- 15860451
TI  - The role of distal arterial reconstruction in patients with diabetic foot
      ischemia.
AB  - The diabetic foot, a common complication that affects patients with diabetes
      mellitus, is a therapeutic challenge. It places an increasing burden on society;
      the patient and caregivers as well as health care systems and clinicians are
      touched by this problem. The management of the diabetic foot with ischemia
      consequent to peripheral arterial disease is vexing, often leading to successive
      amputations. Surgical reconstruction of the peripheral arteries has always been a
      consideration, although the concept of coexistent small vessel disease has
      prejudiced the notion of offering reconstructive surgery to these patients. This
      article examines some of the literature relating to bypass surgery with a view to
      addressing the aforementioned notion. An appraisal of the literature suggests
      that vascular reconstructive surgery offers benefits to the diabetic patient,
      albeit these papers have weaknesses related to study design and methodology.
      Improved studies are indicated to address the role of bypass surgery to help the
      diabetic patient with foot complications; it is reasonable to hope that our
      understanding of the fundamental concepts of the pathogenesis of diabetic foot
      disease will also improve.

PMID- 15860452
TI  - Medical applications of odor-sensing devices.
AB  - Many diseases and intoxications are accompanied by characteristic odors, and
      their recognition can provide diagnostic clues, which in turn may aid in planning
      a therapy. Arrays of gas and odor sensors, made from different technologies, are
      finding their way into a variety of specialized applications. This article
      reviews some clinical applications where this technology can be applied to
      noninvasive monitoring of patients.

PMID- 15860453
TI  - Bleeding complications in patients treated with maggot debridement therapy.

PMID- 15860454
TI  - Re: Bleeding complications in patients treated with maggot debridement therapy,
      Steenvoorde P and Oskam J, IJLEW 2005;4(1):57-58.

PMID- 15860455
TI  - Malignant melanoma and filariasis: a coexistence or an association?
AB  - Malignancy has been reported with chronic lymphedema, especially
      lymphangiosarcoma. The authors report on a patient with lymphedema due to
      filariasis, presenting with an ulcerated pigmented lesion that was malignant
      melanoma. A literature search revealed no previous report of such lesions
      existing together.

PMID- 15860458
TI  - Interferon regulatory factor 1 is an essential and direct transcriptional
      activator for interferon {gamma}-induced RANTES/CCl5 expression in macrophages.
AB  - Interferon regulatory factor 1 (IRF-1) is an important transcription factor in
      interferon gamma (IFNgamma)-mediated signaling in the development and function of
      NK cells and cytotoxic T lymphocytes. RANTES (regulated on activation normal T
      cell expressed and secreted; CCL5) is a member of the CC chemokine family of
      proteins, which is strongly chemoattractant for several important immune cell
      types in host defense against infectious agents and cancer. However, the role of
      IFNgamma and IRF-1 in the regulation of RANTES gene expression and their
      operative mechanisms in macrophages have not been established. We report here
      that RANTES expression in IRF-1-null mice, primarily in macrophages, in response
      to carcinogenic stimulation in vivo and in vitro and to IFNgamma but not to
      lipopolysaccharide in vitro, was markedly decreased. As a result, RANTES-mediated
      chemoattraction of CCR5(+) target cells was also severely impaired. Adenovirus
      mediated gene transduction of IRF-1 in primary macrophages resulted in enhanced
      RANTES expression. The IFNgamma and IRF1 response element was localized to a
      TTTTC motif at -147 to -143 of the mouse RANTES promoter, to which endogenous or
      recombinant IRF-1 can physically bind in vitro and in vivo. This study uncovers a
      novel IFNgamma-induced pathway in RANTES expression mediated by IRF-1 in
      macrophages and elucidates an important host defense mechanism against neoplastic
      transformation.

PMID- 15860457
TI  - Transcriptional regulation of nanog by OCT4 and SOX2.
AB  - Nanog, Sox2, and Oct4 are transcription factors all essential to maintaining the
      pluripotent embryonic stem cell phenotype. Through a cooperative interaction,
      Sox2 and Oct4 have previously been described to drive pluripotent-specific
      expression of a number of genes. We now extend the list of Sox2-Oct4 target genes
      to include Nanog. Within the Nanog proximal promoter, we identify a composite sox
      oct cis-regulatory element essential for Nanog pluripotent transcription. This
      element is conserved over 250 million years of cumulative evolution within the
      eutherian mammals. A Nanog proximal promoter-EGFP (enhanced green fluorescent
      protein) reporter transgene recapitulates endogenous Nanog mRNA expression in
      embryonic stem cells and their differentiated derivatives. Sox2 and Oct4
      interaction with the Nanog promoter was confirmed through mutagenesis and in
      vitro binding assays. Electrophoretic mobility shift assays indicate that the
      Sox2-Oct4 heterodimer forms more efficiently on the composite element within
      Nanog than the similar element within Fgf4. Using chromatin immunoprecipitation,
      we show that Oct4 and Sox2 bind to the Nanog promoter in living mouse and human
      embryonic stem cells. Furthermore, by specific knockdown of Oct4 and Sox2 mRNA by
      RNA interference in embryonic stem cells, we provide genetic evidence for a link
      between Oct4, Sox2, and the Nanog promoter. These studies extend the
      understanding of the pluripotent genetic regulatory network within which the Sox2
      Oct4 complex are at the top of the regulatory hierarchy.

PMID- 15860459
TI  - Regulation of the G(2)/M transition in Xenopus oocytes by the cAMP-dependent
      protein kinase.
AB  - Vertebrate oocytes are arrested in G(2) phase of the cell cycle at the prophase
      border of meiosis I. Progesterone treatment of Xenopus oocytes releases the G(2)
      block and promotes entry into the M phases of meiosis I and II. Substantial
      evidence indicates that the release of the G(2) arrest requires a decrease in
      cAMP and reduced activity of the cAMP-dependent protein kinase (PKAc). It has
      been reported and we confirm here that microinjection of either wild type or
      kinase-dead K72R PKAc inhibits progesterone-dependent release of the G(2) arrest
      with equal potency and that inhibition can be reversed by a second injection of
      the heat-stable inhibitor of PKAc, PKI. However, a mutant enzyme predicted to be
      completely kinase-dead from the crystal structure of PKAc, K72H PKAc, was much
      less inhibitory when carrying additional mutations that block interaction with
      either type I or type II regulatory subunit. Moreover, inhibition by K72H PKAc
      was reversed by PKI at a 30-fold lower concentration and with more rapid kinetics
      compared with wild type PKAc. K72R PKAc was found to have low but detectable
      activity after incubation in an oocyte extract. These results indicate that
      inhibition of the progesterone-dependent G(2)/M transition in oocytes after
      microinjection of dead PKAc reflects either low residual activity or binding to
      regulatory subunits with a resulting net increase in the level of endogenous wild
      type PKAc. Consistent with this hypothesis, the induction of mitosis in Xenopus
      egg extracts by the addition of cyclin B was blocked by wild type PKAc but not by
      K72H PKAc. The identification of substrates for PKAc that maintain cell cycle
      arrest in G(2) remains an important goal for future work.

PMID- 15860460
TI  - A complex dietary supplement extends longevity of mice.
AB  - Key factors implicated in aging include reactive oxygen species, inflammatory
      processes, insulin resistance, and mitochondrial dysfunction. All are exaggerated
      in transgenic growth hormone mice (TGM), which display a syndrome resembling
      accelerated aging. We formulated a complex dietary supplement containing 31
      ingredients known to ameliorate all of the above features. We previously showed
      that this supplement completely abolished the severe age-related cognitive
      decline expressed by untreated TGM. Here we report that longevity of both TGM and
      normal mice is extended by this supplement. Treated TGM showed a 28% increase (p
      < .00008) in mean longevity. An 11% increase in mean longevity was also
      significant (p < .002093) for treated normal mice, compared to untreated normal
      mice. These data support the hypothesis that TGM are a model of accelerated
      aging, and demonstrate that complex dietary supplements may be effective in
      ameliorating aging or age-related pathologies where simpler formulations have
      generally failed.

PMID- 15860461
TI  - Polymorphisms in the oxidized low-density lipoprotein receptor-1 gene and risk of
      Alzheimer's disease.
AB  - The +1073 C/T polymorphism of the oxidized low-density lipoprotein receptor-1
      (OLR1) gene has been reported to be associated with late-onset Alzheimer's
      disease, whereas for the +1071 T/A polymorphism no association was found. We
      genotyped 169 sporadic Alzheimer's disease patients and 264 sex- and age-matched
      nondemented controls from Southern Italy for OLR1 +1073 C/T and +1071 T/A
      polymorphisms and for apolipoprotein E and LBP-1c/CP2/LSF. We also performed
      haplotype analysis. For the +1073 C/T polymorphism, the C allele and the CC
      genotype have been associated with a higher risk for Alzheimer's disease without
      apolipoprotein E or CP2 interaction. The two polymorphisms were in linkage
      disequilibrium, with the haplotype T-C at significant increased risk of
      developing Alzheimer's disease in the whole sample and in elderly persons 70
      years or older. In our population, the +1073 C/T OLR1 polymorphism exhibited a
      significant association with Alzheimer's disease, further supporting the role of
      OLR1 as a candidate risk gene for sporadic Alzheimer's disease.

PMID- 15860462
TI  - Mismatch repair system and aging: microsatellite instability in peripheral blood
      cells from differently aged participants.
AB  - Age-related alterations of DNA repair could be involved in the accumulation of
      genetic damage with age. Few data suggest a possible alteration with age of the
      mismatch repair system, evidenced by the acquisition of microsatellite
      instability. We aimed to point out a possible implication of this repair system
      in the accumulation of genetic damage with age. Peripheral blood cell DNA from
      226 participants, 110 young (25-35 years), 58 old (85-97 years), and 58
      centenarian was analyzed at five polymorphic microsatellite loci (CD4, p53,
      VWA31, TPOX, and FES/FPS) to point out age-related instabilities or modifications
      in allele frequencies. FES/FPS microsatellite was the most instable, showing both
      the appearance of trizygosis in DNA from old participants and differences in
      allele patterns among age groups, thus indicating an association between
      increased microsatellite instability and aging, one of the possible causes of
      which being an impairment of mismatch repair system capacity with age.

PMID- 15860463
TI  - Evidence for down-regulation of phosphoinositide 3-kinase/Akt/mammalian target of
      rapamycin (PI3K/Akt/mTOR)-dependent translation regulatory signaling pathways in
      Ames dwarf mice.
AB  - How growth hormone (GH) stimulates protein synthesis is unknown. Phosphoinositide
      3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathways
      balance anabolic and catabolic activities in response to nutrients and growth
      factor signaling. As a test of GH signaling, immunoassays of two downstream
      translation regulatory proteins were compared in ad libitum-fed 2-month-old
      normal and Ames (Prop1df) dwarf mice. Phosphorylation of the p70 and p85 isoforms
      of S6 kinase 1 in liver and the p70 isoform in gastrocnemius muscle were
      significantly decreased in dwarfs. Messenger RNA (mRNA) Cap-binding demonstrated
      significantly higher levels of translation repressor 4E-BP1/eukaryotic initiation
      factor 4E (eIF4E) (coprecipitates) from dwarf livers, but not muscle. Consistent
      with these binding data, significantly less phosphorylation of 4E-BP1 was
      documented in dwarf liver. These data suggest a link between GH signaling and
      translation control in a model of extended longevity.

PMID- 15860464
TI  - Mutation screening and association study of the neprilysin gene in sporadic
      Alzheimer's disease in Chinese persons.
AB  - Neprilysin has been reported to be a major beta-amyloid peptide (Abeta)-degrading
      enzyme. The decreased expression and activity of it may contribute to the
      development of Alzheimer's disease by promoting the accumulation of Abeta. We
      used denaturing high-performance liquid chromatography to screen the neprilysin
      gene (NEP) for single nucleotide polymorphisms (SNPs) in 257 Chinese sporadic
      Alzheimer's disease patients and 242 cognitive normal controls. As a result,
      eight novel and one known SNP were identified. Three of them, -204G-->C in the
      promoter region, IVS17-294C-->T, and IVS22+36C-->A showed a significant
      association with Alzheimer's disease (p = .006,.017, and.003, respectively).
      Subsequent haplotype analysis provided further evidence of the association
      (global p < .0001 for the three SNPs mentioned above, and global p < .01 for the
      eight SNPs with rare allele frequency > 1%). These findings indicate that genetic
      variations within or extremely close to NEP might influence the susceptibility to
      Alzheimer's disease in Chinese persons.

PMID- 15860465
TI  - Effect of exercise training on peak aerobic power, left ventricular morphology,
      and muscle strength in healthy older women.
AB  - The effect that aerobic (AT) and/or strength training (ST) has on altering peak
      aerobic power (VO2peak), muscle strength, left ventricular (LV) morphology, and
      diastolic filling in healthy older women is not known. We assessed the effects of
      12 weeks of AT, ST, combined aerobic and strength training (COMT), or no training
      (NT) on VO2peak, muscle strength, LV morphology, and diastolic filling in 31
      healthy women (68 +/- 4 years). Relative VO2peak was significantly greater after
      12 weeks of AT, ST, or COMT. Upper and lower extremity strength were
      significantly higher after 12 weeks of ST or COMT with no change after AT or NT.
      LV morphology and diastolic filling were not altered after 12 weeks of AT, ST,
      COMT, or NT. Twelve weeks of ST or COMT are as effective as 12 weeks of AT for
      increasing relative VO2peak, however, ST and COMT are more effective than AT for
      improving overall muscle strength.

PMID- 15860466
TI  - Aging effects on the metabolic and cognitive energy cost of interlimb
      coordination.
AB  - Many everyday motor tasks have high metabolic energy demands, and some require
      extended practice to learn the required coordination between limbs. Eight older
      (73.1 +/- 4.4 years) and 8 younger (23.3 +/- 5.9) men practiced a high-energy two
      hand coordination task with both 180 degrees and 90 degrees target relative
      phase. The older group showed greater performance error in both conditions, and
      performance at 90 degrees was strongly attracted to antiphase coordination (180
      degrees). In a retention test one week following the acquisition trials, the
      older group had learned the 180 degrees condition but did not learn the 90
      degrees condition. Metabolic energy cost was not different between groups, but
      the older men showed higher heart rate and both conditions imposed greater
      cognitive demands as revealed in auditory probe reaction time. Older adults'
      motor learning may be inhibited by elevated heart rate at the same oxygen cost,
      increased cognitive cost, and an attraction toward more established low-energy in
      phase or antiphase coordination.

PMID- 15860468
TI  - Stability and sensitivity of nursing home quality indicators.

PMID- 15860469
TI  - Muscle mass, muscle strength, and muscle fat infiltration as predictors of
      incident mobility limitations in well-functioning older persons.
AB  - BACKGROUND: Lower muscle mass has been correlated with poor physical function;
      however, no studies have examined this relationship prospectively. This study
      aims to investigate whether low muscle mass, low muscle strength, and greater fat
      infiltration into the muscle predict incident mobility limitation. METHODS: Our
      study cohort included 3075 well-functioning black and white men and women aged 70
      79 years participating in the Health, Aging, and Body Composition study.
      Participants were followed for 2.5 years. Muscle cross-sectional area and muscle
      tissue attenuation (a measure of fat infiltration) were measured by computed
      tomography at the mid-thigh, and knee extensor strength by using a KinCom
      dynamometer. Incident mobility limitation was defined as two consecutive self
      reports of any difficulty walking one-quarter mile or climbing 10 steps. RESULTS:
      Mobility limitations were developed by 22.3% of the men and by 31.8% of the
      women. Cox's proportional hazards models, adjusting for demographic, lifestyle,
      and health factors, showed a hazard ratio of 1.90 [95% confidence interval (CI),
      1.27-2.84] in men and 1.68 (95% CI, 1.23-2.31) in women for the lowest compared
      to the highest quartile of muscle area (p <.01 for trend). Results for muscle
      strength were 2.02 (95% CI, 1.39-2.94) and 1.91 (95% CI, 1.41-2.58), p <.001
      trend, and for muscle attenuation were 1.91 (95% CI, 1.31-2.83) and 1.68 (95% CI,
      1.20-2.35), p <.01 for trend. When included in one model, only muscle attenuation
      and muscle strength independently predicted mobility limitation (p < .05). Among
      men and women, associations were similar for blacks and whites. CONCLUSION: Lower
      muscle mass (smaller cross-sectional thigh muscle area), greater fat infiltration
      into the muscle, and lower knee extensor muscle strength are associated with
      increased risk of mobility loss in older men and women. The association between
      low muscle mass and functional decline seems to be a function of underlying
      muscle strength.

PMID- 15860470
TI  - Expanding the disablement process model among older Mexican Americans.
AB  - BACKGROUND: Very few studies have examined how disability develops among older
      Mexican Americans. To determine how disability develops, we explored the
      Disablement Process model, which posits that impairment, measured by muscle
      strength, leads to functional limitations, which lead to disability, which
      ultimately is associated with health-related quality of life (HRQOL). METHODS: A
      structural equation model approach was used (AMOS 4) with data collected on 622
      Mexican Americans aged 71 or older residing in the Southwest. RESULTS: Our
      results show preliminary support for the Disablement Process model. Impairment is
      significantly associated with functional limitation (beta =.36, z value = 7.2),
      which is significantly associated with disability (beta = -.53, z value = 16.1).
      Finally, disability is significantly related to both physical and mental
      components of HRQOL (beta = -.69, z value = 23.4; beta = -.26, z value = 6.5,
      respectively). CONCLUSIONS: Muscle strength as a measure of impairment and the
      Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) score as a
      measure of HRQOL are important factors in understanding disability in older
      Mexican Americans.

PMID- 15860471
TI  - Randomized controlled drug trials on very elderly subjects: descriptive and
      methodological analysis of trials published between 1990 and 2002 and comparison
      with trials on adults.
AB  - BACKGROUND: Very elderly subjects (VES; aged 80 years or older) constitute a
      special population as they frequently present multiple diseases (polypathology).
      Results from trials on general adult populations therefore cannot be extrapolated
      to VES. We performed a census of randomized controlled trials (RCT) on VES
      published between 1990 and 2002, and carried out a descriptive and methodological
      analysis of these RCT/VES, comparing them with matched RCT on general adult
      populations (control RCT, RCT/C). METHODS: We searched for RCT/VES in two
      international databases (EMBASE and MEDLINE) and then manually. RCT/C were
      matched to RCT/VES for disease area and year of publication. The methodological
      quality of each RCT was assessed with Chalmers' scale. RESULTS: We identified 84
      RCT/VES, 63 of which were conclusive and 21, inconclusive. Subjects were
      institutionalized in 48 RCT, and community dwelling in 11 RCT (unspecified in 25
      RCT). Efficacy was the main criterion in 75 RCT; tolerance in 9 RCT. Twenty-six
      RCT were published by geriatrics journals, and 58 by general medical journals.
      The RCT/VES covered most of the disease areas of geriatrics. The 84 RCT/VES had a
      mean methodological quality score of 0.578 +/- 0.157. The matched 84 RCT/C had a
      mean methodological quality score of 0.592 +/- 0.116 (p = .466). The
      methodological quality score of RCT/VES increased with the number of included
      subjects (p = .004) and the year of publication (p = .001). CONCLUSIONS: The
      methodological quality of RCT/VES is equivalent to that of RCT in general adult
      populations. Nevertheless, RCT/VES remain very scarce, and neglect certain
      diseases. RCT/VES and the inclusion of very elderly subjects in RCT on adults
      should be strongly encouraged.

PMID- 15860472
TI  - Physical disability contributes to caregiver stress in dementia caregivers.
AB  - BACKGROUND: Previous findings of studies on the impact of physical illness on
      caregiver health have been inconsistent. The authors wanted to determine whether
      physical disability, as determined by the SF-12 survey that provides information
      on both physical and mental health problems, contributes to caregiver stress.
      METHODS: The authors interviewed 91 primary caregivers (aged 38-85 years) of
      persons with dementia who had been referred by their family physicians for the
      first time for formal support services or memory evaluation. Caregivers completed
      the SF-12 version of the Medical Outcomes Study Short Form Health Survey that
      generates Mental Component Summary (MCS) and Physical Component Summary (PCS)
      scores and reported on caregiver stress and concurrent medical conditions and
      medications. RESULTS: Most caregivers reported stress (76.9%), having medical
      conditions (72.4%), or taking medications (67%). The MCS but not the PCS scores
      were significantly lower than community norms, indicating an excess of disability
      due to mental health problems. Nevertheless, 40.7% had PCS scores indicating some
      degree of physical disability. Using multiple logistic regression analysis, PCS
      scores but not the presence of medical problems were independently associated
      with caregiver stress. CONCLUSIONS: Chronic disability as assessed by SF-12 PCS
      scores is independently associated with caregiver stress. These data suggest that
      caregivers of persons with dementia should be assessed for disabling physical
      conditions and mental health problems. In addition, reducing the impact of
      physical disability could ameliorate caregiver stress.

PMID- 15860473
TI  - Relationship between lung function and physical performance in disabled older
      women.
AB  - BACKGROUND: Understanding the association between lung function and physical
      performance in disabled older women helps in determining the potential for
      prevention and treatment strategies to decrease disability. The aim of this study
      was to determine the association of lung function with objective and self
      reported physical performance in community-dwelling disabled older women.
      METHODS: The Women's Health and Aging Study I consists of 1002 disabled community
      dwelling women aged > or = 65. Of these women, 840 underwent spirometry with
      determination of forced expiratory volume in one second (FEV1) and forced vital
      capacity (FVC). Cross-sectional analyses included multivariate linear regression
      to assess the association between FEV1, FVC, FEV1/FVC, and the time to walk four
      meters after adjusting for confounders, including age, race, geriatric depression
      scale score, body mass index, muscle strength, osteoarthritis, smoking status,
      and cardiovascular disease. Multiple logistic regression was used to assess the
      association between FEV1, FVC, FEV1/FVC, and self-reported disability in physical
      performance. RESULTS: FEV1 was independently associated with time to walk 4
      meters. For every 100 ml decrease in FEV1, there was a 0.15-second (95%
      confidence interval: 0.24 to 0.06) increase in time to walk 4 meters. There was
      an 8% increase in the prevalent odds of self-reported disability in physical
      performance for every 100 ml decrease in FEV1. FVC was also associated with
      physical performance measures. In contrast, FEV1/FVC was associated with
      objective but not subjective physical performance. CONCLUSION: Decreasing lung
      function is independently associated with decrements in objective and self
      reported physical performance in disabled older women.

PMID- 15860474
TI  - Fear of falling and related activity restriction among middle-aged African
      Americans.
AB  - BACKGROUND: The prevalence of fear of falling and related activity restriction,
      and their joint distribution with falls and falls efficacy, have been
      inadequately addressed in population-based studies of middle-aged and African
      American groups. METHODS: The African American Health project is a population
      based panel study of 998 African Americans born in 1936-1950 from two areas of
      metropolitan St. Louis (an impoverished inner-city area and a suburban area).
      Fear of falling, fear-related activity restriction, and 24 frailty-related
      covariates were assessed during in-home evaluations in 2000-2001. RESULTS: We
      found that 12.6% of participants reported having fear of falling without activity
      restriction, 13.2% had fear of falling with activity restriction, and 74.2% had
      no fear of falling. Neither fear of falling nor fear-related activity restriction
      varied significantly across three birth cohorts (1946-1950, 1941-1945, and 1936
      1940). Lack of overlap of these two phenomena with having a fall in the past 2
      years and low falls efficacy was considerable. When examined across three groups
      (no fear, fear without activity restriction, and fear with activity restriction),
      a consistent pattern of decreasing health status and social, emotional, and
      physical functioning was demonstrated. CONCLUSIONS: In this population-based
      sample of 49- to 65-year-old African Americans, fear of falling and fear-related
      activity restriction were surprisingly common and not well explained by prior
      falls or low falls efficacy. These phenomena were already evident by age 49-55.
      Further study is warranted, including detailed qualitative investigations
      examining the timing, precursors, and consequences of fear of falling and fear
      related activity restriction in minority and majority populations.

PMID- 15860475
TI  - Circulating acute phase mediators and skeletal muscle performance in hospitalized
      geriatric patients.
AB  - BACKGROUND: There is growing evidence for the significant involvement of
      inflammatory processes in the development of muscle wasting in old age.
      Therefore, any disease accompanied by inflammation can be threatening to the
      muscle function in geriatric patients. METHODS: Sixty-three hospitalized
      geriatric patients (42 female, 21 male; mean age 84.2 +/- 5.7 years) were
      monitored weekly for muscle function (grip strength, fatigue resistance, shoulder
      extension strength, and hip extension strength) and for concentration of
      circulating C-reactive protein (CRP), fibrinogen, interleukin 6 (IL-6), and tumor
      necrosis factor-alpha alpha (TNF-alpha). RESULTS: On the basis of circulating CRP
      and fibrinogen concentrations, 42 patients were categorized on admission as
      inflammatory and 21 as noninflammatory. Inflammatory patients presented
      significantly weaker grip strength, shoulder extension strength, and a worse
      fatigue resistance than did noninflammatory patients. These muscle functions were
      negatively correlated with the concentrations of circulating CRP and IL-6, but
      not with fibrinogen or TNF-alpha. In noninflammatory patients, the fatigue
      resistance improved significantly during the first week of hospitalization. In
      patients admitted with inflammation, no improvement of muscle function was
      observed. Patients who remained inflammatory for 2 weeks or more presented a
      significant worsening of fatigue resistance. CONCLUSIONS: Geriatric hospitalized
      patients presenting with inflammation show significantly worse muscle functions,
      which do not improve during hospitalization despite adequate treatment of the
      primary disease. Reduced strength and fatigue resistance are significantly
      related to the concentration of circulating CRP and IL-6. Standard treatment of
      the underlying illness and classic physical therapy are not sufficient to
      normalize the skeletal muscle strength and fatigue resistance in these
      hospitalized patients.

PMID- 15860476
TI  - Maintenance of effects of the home environmental skill-building program for
      family caregivers and individuals with Alzheimer's disease and related disorders.
AB  - BACKGROUND: Few studies evaluate whether short-term intervention effects are
      maintained over time for families caring for persons with dementia. This article
      examines whether treatment effects found at 6 months following active treatment
      were sustained at 12 months for 127 family caregivers who participated in an
      occupational therapy intervention tested as part of the National Institutes of
      Health Resources for Enhancing Alzheimer's Caregiver Health (REACH) initiative.
      METHODS: A randomized two-group design was implemented with three assessment
      points: baseline, 6 months, and 12 months. Caregivers were randomly assigned to a
      usual care control group or intervention that consisted of six occupational
      therapy sessions to help families modify the environment to support daily
      function of the person with dementia and reduce caregiver burden. Following 6
      month active treatment, a maintenance phase consisted of one home and three brief
      telephone sessions to reinforce strategy use and obtain closure. Non-inferiority
      statistical analysis was used to evaluate whether intervention caregivers
      maintained treatment benefits from 6 to 12 months in comparison to controls.
      RESULTS: For the sample of 127 at 6 months, caregivers in intervention reported
      improved skills (p = .028), less need for help providing assistance (p = .043),
      and fewer behavioral occurrences (p = .019) compared to caregivers in control. At
      12 months, caregiver affect improved (p = .033), and there was a trend for
      maintenance of skills and reduced behavioral occurrences, but not for other
      outcome measures. CONCLUSION: An in-home skills training program helps sustain
      caregiver affect for those enrolled for more than 1 year. More frequent
      professional contact and ongoing skills training may be necessary to maintain
      other clinically important outcomes such as reduced upset with behaviors.

PMID- 15860477
TI  - Apolipoprotein epsilon4 allele and problems with orientation are associated with
      a persistent decline in cognition in community-dwelling elderly persons.
AB  - BACKGROUND: A decline in cognitive test scores in elderly persons can signal the
      beginning of a descent into dementia or may indicate only a short-term cognitive
      disturbance. It would be clinically useful to distinguish between the two
      outcomes and to identify characteristics of each. METHODS: Four hundred thirty
      seven community-dwelling elderly persons were given the Mini-Mental State
      Examination (MMSE) annually for an average of 7 years. A low score between
      baseline and final MMSE was identified. A low score 3 or more points lower than
      baseline score indicated cognitive decline. This decline was called persistent if
      the final MMSE score was also at least 3 points lower than baseline MMSE score;
      otherwise, the decline was considered transient. RESULTS: Twenty participants
      (4.6%) experienced a persistent cognitive decline, 67 participants (15.3%)
      experienced a transient cognitive decline. Presence of the apolipoprotein
      epsilon4 allele was significantly associated with persistent cognitive decline
      (age-adjusted odd ratio [OR] = 11.46, p < .0001) but not with transient cognitive
      decline (age-adjusted OR = 1.53, p = .219). Incorrect answers on the orientation
      part of the MMSE at the time of cognitive decline was associated with persistent
      decline compared to transient decline (age-adjusted OR = 3.58, p = .058).
      CONCLUSIONS: Persistent cognitive decline is an infrequent occurrence in
      community-dwelling elderly persons. Presence of the epsilon4 allele and errors
      made by the subject on questions of orientation may be useful in determining
      whether a cognitive decline is likely to be persistent.

PMID- 15860478
TI  - Reading aloud and arithmetic calculation improve frontal function of people with
      dementia.
AB  - BACKGROUND: Recent findings of neuroimaging studies indicate that reading aloud
      and arithmetic calculation activate bilateral dorsolateral prefrontal cortex of
      humans. The purpose of this study was to measure the effect of reading aloud and
      arithmetic calculation, by elderly people who were clinically diagnosed with
      dementia Alzheimer type, on their brain functions and activities of daily living.
      METHODS: Sixteen experimental and 16 age- and Mini-Mental State Examination score
      matched control subjects participated. The participants in the experimental group
      were asked to perform a training program using learning tasks in reading and
      arithmetic for 2-6 days a week. The function of the frontal cortex of the
      subjects was assessed by FAB at bedside (Frontal Assessment Battery). RESULTS:
      After 6 months of training, the FAB score of the experimental group showed a
      statistically significant improvement. The FAB score of the control group
      decreased slightly over the 6-month period, and the difference between the scores
      of the experimental and control groups was statistically significant. We also
      observed the restoration of communication and independence in the experimental
      group. CONCLUSION: Our results indicate that learning tasks of reading aloud and
      arithmetic calculation can be used for cognitive rehabilitation of dementia
      patients.

PMID- 15860479
TI  - Age, hormones, and cognitive functioning among middle-aged and elderly men: cross
      sectional evidence from the Massachusetts Male Aging Study.
AB  - BACKGROUND: This study examines interrelationships among age, hormones, and
      cognition for middle-aged and elderly men, and tests whether hormones predict
      lower cognitive functioning and mediate the age-cognition relationship. METHODS:
      We analyzed Time 2 data from the Massachusetts Male Aging Study, a population
      based cohort study. Selection criteria included complete information on cognition
      and hormones (n = 981). Cognitive measures included working memory (Backward
      Digit Span test), speed/attention (Digit Symbol Substitution test), and spatial
      ability (Figural Relations test). Hormones included free testosterone, total
      testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate
      (DHEAS), androstanediol glucuronide (3 alpha-A-diol-gluc), luteinizing hormone
      (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin
      (alternatively known as a "binding protein") (SHBG), prolactin (PRL), estrone
      (E1), and cortisol (CRT). Age was measured in years. Adjusted analyses added
      educational attainment, health conditions and behaviors, body mass index, and
      depression. RESULTS: Older age was associated with lower cognitive functioning.
      In unadjusted models, logged free and total testosterone, DHEA, and DHEAS related
      to higher functioning in at least one cognitive domain; logged FSH, SHBG, and LH
      related to lower functioning in at least one cognitive domain; and logged E1,
      CRT, and PRL were not significant. In adjusted models, logged hormones did not
      relate to cognitive function except for logged E1 and CRT, which had negative
      effects. Logged hormones did not mediate the age-cognition relationship.
      CONCLUSIONS: The direct effects of hormones on cognition are not significant when
      salient factors are considered. Further, hormones do not mediate the age
      cognition relationship; it is necessary to look to other explanatory pathways.

PMID- 15860480
TI  - Swallow respiratory patterns and aging: presbyphagia or dysphagia?
AB  - BACKGROUND: Assessment referrals are increasing for unexpected dysphagia,
      particularly for older people. It is unclear if this is due to more impaired
      swallows or healthy age-related changes. Swallow respiration coordination
      prevents aspiration, and may deteriorate with age. Nonpathological features of
      the swallow in healthy aging and the factors that influence an individual's
      ability to eat and drink safely need greater understanding. Some changes might
      predispose an older person to dysphagic complications in the event of an insult
      such as a stroke. We investigated the effects of healthy aging on resting and
      swallow respiratory patterns. METHODS: Fifty healthy volunteers (aged 20-78
      years) were recruited to have swallow respiration patterns recorded on a
      computer. Bolus volume and consistency variations were studied: 5 and 20 ml of
      water and 5 ml of yogurt. RESULTS: Measurable swallows significantly decreased
      with age for water boluses. Swallow apnea increased with age (5 ml of water r =
      0.433, p = .002; 5 ml of yogurt r = 0.367, p = .023). Independent of age were:
      breathing out (occurred after 98% of boluses); multiple swallowing (occurred with
      all bolus types); post-swallow respiration reset pattern (more irregular after
      yogurt, Wilcoxon signed rank Z = -2.236, p = .025); and resting respiration.
      CONCLUSIONS: Subtle changes occur in swallow respiration coordination with age.
      These changes may be compensatory protective mechanisms rather than the result of
      decreased muscle mobility or reaction times, and not indicative of impairment.
      Misattributing healthy age-related changes to impairment affects patient care and
      the use of healthcare resources.

PMID- 15860481
TI  - Endonasal geometry changes in elderly people: acoustic rhinometry measurements.
AB  - BACKGROUND: Skeletal nasal changes in elderly people have been extensively
      investigated, but data on variation of the endonasal architecture with age do not
      exist. We evaluated endonasal parameters in an elderly population as compared
      with those in a young group. METHODS: Acoustic rhinometry measurements were
      performed on 165 participants in the age range of 20-93 years. The rhinograms
      provided the endonasal volume from the nostril entrance to a 7.0 cm cephalic
      point (V0-7) and the minimal cross-sectional areas (MCA1 and MCA2). Statistical
      analysis was performed by Pearson correlation and one-way analysis of variance,
      using age as a continuous or categorical variable. RESULTS: There was no
      statistical difference in gender distribution within each age group. The results
      obtained for the left and right nostrils were similar. Endonasal volume V0-7 and
      the narrowing areas MCA1 and MCA2 significantly increase with age, except for men
      over 80 years in which a relative decrease was observed. CONCLUSION: Acoustic
      rhinometry examination of the endonasal architecture in a healthy young and
      elderly population demonstrated a gradual increase of endonasal volumes and
      minimal cross-sectional areas with age.

PMID- 15860482
TI  - Driving cessation and increased depressive symptoms.
AB  - BACKGROUND: To understand the consequences of driving cessation in older adults,
      the authors evaluated depression in former drivers compared with active drivers.
      METHODS: Depression (as assessed using the Center for Epidemiological Studies
      Depression Scale), driving status, sociodemographic factors, health status, and
      cognitive function were evaluated for a cohort of 1953 residents of Sonoma
      County, California, aged 55 years and older, as part of a community-based study
      of aging and physical performance. The authors re-interviewed 1772 participants
      who were active drivers at baseline 3 years later. RESULTS: At baseline, former
      drivers reported higher levels of depression than did active drivers even after
      the authors controlled for age, sex, education, health, and marital status. In a
      longitudinal analysis, drivers who stopped driving during the 3-year interval
      (i.e., former drivers) reported higher levels of depressive symptoms than did
      those who remained active drivers, after the authors controlled for changes in
      health status and cognitive function. Increased depression for former drivers was
      substantially higher in men than in women. CONCLUSIONS: With increasing age, many
      older adults reduce and then stop driving. Increased depression may be among the
      consequences associated with driving reduction or cessation.

PMID- 15860483
TI  - Ear diseases in elderly hospital patients in Nigeria.
AB  - BACKGROUND: Little information is available about the pattern of ear diseases in
      the elderly population. Therefore, the present study aims to determine the
      pattern of ear diseases among elderly Nigerians, so as to provide an objective
      basis for cost-effective health care planning for the emerging geriatric
      population. METHODS: A retrospective study of 320 patients aged 60 years or older
      presenting with ear diseases at the University of Ilorin Teaching Hospital,
      Ilorin, Nigeria, between January 1996 and December 2001 was carried out. RESULTS:
      Impacted cerumen was the most common ear disease, occurring in 110 (34.4%)
      patients of the study population. Chronic suppurative otitis media (CSOM) was the
      most common infectious disease, affecting 28 (8.8%) patients. Of the 88 patients
      with hearing loss, 63 (71.6%) had sensorineural, 20 (22.7%) had presbycusis, 1
      (1.1%) had conductive, and 4 (4.6%) had mixed hearing loss. CONCLUSION: Our data
      suggest that impacted cerumen, hearing loss, and infections (notably CSOM), are
      the common ear diseases among elderly Nigerians.

PMID- 15860484
TI  - Influences of body composition upon the relative metabolic and cardiovascular
      demands of load-carriage.
AB  - AIM: To test the hypothesis that measures of aerobic fitness, body mass and
      indices of body composition will influence the metabolic and cardiovascular
      demands of simulated load-carriage tasks. METHOD: Twenty-eight healthy male
      volunteers, following assessment of maximal oxygen uptake (O(2)max) and body
      composition, walked on a treadmill at 4 kph (1.11 m/s) for 60 min on gradients of
      0, 3, 6 and 9% whilst carrying backpack loads of 0, 20 and 40 kg. During the
      final 3 min of each 5-min exercise bout, indirect respiratory calorimetry and
      heart rate data were collected and the 'steady-state' metabolic O(2) and
      cardiovascular (heart rate) demands quantified. RESULTS: Absolute O(2)max
      (ml/min) produced the strongest correlation (r = -0.64, P < 0.01) with the
      metabolic demand of heavy load-carriage (40 kg). The body composition index lean
      body mass/(fat mass + external load) produced a moderate correlation (r = -0.52,
      P < 0.01) with the metabolic demand of heavy load-carriage. The increases in
      metabolic and cardiovascular demands were greater when the load carried increased
      from 20 to 40 kg compared with 0 to 20 kg at all four gradients. A model
      incorporating anthropometric and physiological characteristics with gradient and
      load explains 89% of the variability in the metabolic demands of load-carriage
      compared with 82% using gradient and load alone. CONCLUSION: The results show
      that indices of body composition as well as absolute aerobic power influence the
      relative metabolic demands of load-carriage. Application of these measurements
      would ensure selection criteria for load-carriage occupations are based on lean
      muscle mass rather than running speed.

PMID- 15860485
TI  - Improving the quality of peak flow measurements for the diagnosis of occupational
      asthma.
AB  - INTRODUCTION: Serial measurements of peak expiratory flow (PEF) are recommended
      in the evidence-based review list as the first stage in objective confirmation of
      occupational asthma. Different centres have reported widely different success in
      obtaining records of sufficient data quantity for diagnosis. We investigated
      different methods of instruction and determined the return rate and quality of
      the resulting record for the diagnosis of occupational asthma. METHODS:
      Consecutive new referrals were recruited from a specialized occupational lung
      disease clinic and requested to carry out serial PEFs for the assessment of
      suspected occupational asthma. Requests to carry out the records were either from
      written postal instructions or personal instruction from a PEF specialist. Record
      quality received from other clinicians was also analysed separating those using
      dedicated occupational forms, and those submitting on graph type forms. RESULTS:
      The postal return rate was 56% and the personal rate 85%. The number of records
      fulfilling all the data quality criteria were similar in the postal and personal
      groups (55 and 59%, respectively). Pre-existing records from other clinics
      plotted from graph charts (fulfilling all criteria) were only adequate in 23%,
      compared with 61% adequate for pre-existing records plotted from occupational
      forms. Failure of the record to contain consecutive work periods of > or =3
      workdays was the most common failure. CONCLUSION: The return rate of PEFs for
      diagnosing occupational asthma is better when patients have been given specific
      instructions from a PEF specialist and the data quantity better when recorded on
      a dedicated form.

PMID- 15860486
TI  - A randomized, multicenter study of subcutaneous and intravenous darbepoetin alfa
      for the treatment of chemotherapy-induced anemia.
AB  - BACKGROUND: This randomized, open-label study evaluated the efficacy, safety and
      pharmacokinetics of darbepoetin alfa administered intravenously (i.v.) or
      subcutaneously (s.c.) in chemotherapy-induced anemia. PATIENTS AND METHODS:
      Patients received darbepoetin alfa i.v. (n=59) or s.c. (n=59) at a dose of 4.5
      mug/kg once weekly for 6 weeks (correction phase) followed by 4.5 mug/kg once
      every 3 weeks for the remainder of the 18-week treatment period (maintenance
      phase). RESULTS: During the correction phase, the mean [95% confidence interval
      (CI)] change in hemoglobin (intention-to-treat) was 1.1 (0.6-1.5) g/dl in the
      i.v. group and 1.3 (0.9-1.7) g/dl in the s.c. group; using available data, the
      mean change was 1.4 (1-1.9) g/dl and 1.6 (1.2-2) g/dl, respectively. The
      percentage (95% CI) of patients maintaining hemoglobin (i.e. average decrease <
      or =0.5 g/dl) during the maintenance phase was similar between the i.v. (82%; 95%
      CI 66% to 92%) and s.c. (80%; 95% CI 66% to 90%) groups. Thirty-five per cent
      (95% CI 20% to 50%) of patients in the i.v. group and 32% of patients in the s.c.
      group (95% CI 18% to 45%) received red blood cell transfusions during week 5 to
      the end of the treatment period. Darbepoetin alfa was well tolerated in both
      groups. No significant difference (P=0.36) in weekly darbepoetin alfa serum
      concentrations was observed between groups. CONCLUSIONS: Darbepoetin alfa can be
      administered i.v. or s.c. at equal doses for the treatment of anemia in this
      setting.

PMID- 15860487
TI  - Randomized phase III trial comparing cisplatin-etoposide to carboplatin
      paclitaxel in advanced or metastatic non-small cell lung cancer.
AB  - BACKGROUND: The present study was designed to evaluate the efficacy and safety of
      the regimen of carboplatin plus paclitaxel (investigational arm) versus the
      reference regimen of cisplatin plus etoposide for the treatment of advanced or
      metastatic non-small-cell lung cancer. PATIENTS AND METHODS: A total of 369
      patients were enrolled, 179 on arm A (cisplatin 75 mg/m2 and etoposide 100 mg/m2)
      and 190 on arm B (carboplatin AUC=6 mg/ml min and paclitaxel 225 mg/m2), with
      cycles repeated every 3 weeks. The arms were well balanced with respect to age,
      performance status, weight loss, stage of disease and disease measurability.
      However, significantly more women were randomized to arm A than to arm B
      (P=0.039). RESULTS: The objective response rate (ORR) was 15% on arm A compared
      with 23% on arm B (P=0.061). Median survival time, time to progression and 1-year
      survival rates for arms A and B were 274 days and 233 days (P=0.086), 111 days
      and 121 days (P=0.877), and 37% and 32%, respectively. The most prevalent
      toxicities were neutropenia and leukopenia and they occurred at a higher rate in
      arm A than in arm B. CONCLUSION: There was no statistically significant survival
      advantage for carboplatin-paclitaxel compared with cisplatin-etoposide. However,
      there was an overall benefit in quality of life with the carboplatin-paclitaxel
      regimen.

PMID- 15860488
TI  - Advanced bronchioloalveolar carcinoma: a phase II trial of paclitaxel by 96-hour
      infusion (SWOG 9714): a Southwest Oncology Group study.
AB  - BACKGROUND: There are no published prospective trials of chemotherapy for
      advanced bronchioloalveolar carcinoma (BAC), a subtype of non-small-cell lung
      cancer for which there is no current standard therapy. This phase II study
      assesses the efficacy and toxicity of 96-h paclitaxel in chemotherapy-naive
      patients with advanced BAC. PATIENTS AND METHODS: Patients with histologically
      confirmed stage IIIB (with pleural effusion) or stage IV BAC were eligible.
      Treatment consisted of paclitaxel 35 mg/m2/24 h continuously infused over 96 h
      (days 1-4) every 21 days for up to six courses. RESULTS: A total of 58 eligible
      patients were enrolled. The objective response rate was 14% (all partial
      responses, 9% confirmed); 40% of patients demonstrated stable disease. The median
      progression-free and overall survivals were 5 and 12 months, respectively. Grade
      3 or greater toxicities included neutropenia/granulocytopenia (43%), febrile
      neutropenia (12%), infection (22%), and stomatitis/pharyngitis (10%); there were
      five treatment-related deaths. CONCLUSIONS: S9714 represents the first
      prospective multi-institutional cooperative group trial focusing on treatment
      outcomes in BAC. Studies targeting this population are feasible, and while first
      line paclitaxel administered as a prolonged infusion is active in this setting,
      toxicities limits the utility of this regimen. S9714 serves as a historical
      control for BAC patients against which future therapeutic approaches can be
      compared.

PMID- 15860489
TI  - Improvement of delivery and live birth rates after ICSI in women aged >40 years
      by ovarian co-stimulation with growth hormone.
AB  - BACKGROUND: Growth hormone (GH) is required for ovarian follicular development,
      and its administration during ovarian stimulation improves pregnancy rate in cow
      and sheep. Data on the use of exogenous GH in human assisted reproduction
      treatment are inconsistent. This prospective randomized study evaluates the
      usefulness of GH administration in women of >40 years undergoing ovarian
      stimulation for assisted reproduction treatment. METHODS: One hundred women of
      >40 years undergoing assisted reproduction treatment were randomized between a GH
      treatment group and a placebo group. Assisted reproduction treatment outcomes
      were evaluated. RESULTS: In patients of the GH treatment group, a similar number
      of oocytes, embryos and pregnancies was achieved as compared with the placebo
      group. However, the patients treated with GH suffered fewer pregnancy losses,
      resulting in higher delivery and live birth rates. These patients also showed
      higher peak serum estradiol concentration and higher concentrations of GH and
      estradiol in pre-ovulatory follicular fluid as compared with the placebo group.
      CONCLUSIONS: Administration of GH during ovarian stimulation alleviates age
      related decrease in assisted reproduction treatment efficiency. This effect
      appears to be mainly due to an improvement of oocyte developmental potential, but
      GH action on the uterus cannot be excluded.

PMID- 15860490
TI  - Familial prevalence of uterine fibroids is associated with distinct clinical and
      molecular features.
AB  - BACKGROUND: Although uterine fibroids are very common, their pathogenesis and
      clinical behaviour are poorly understood. Since they may be prevalent in some
      families, we investigated whether such a prevalence was associated with
      distinctive clinical and molecular features. METHODS: A case-control
      questionnaire study of 300 multi-ethnic women with uterine fibroids at a London
      university hospital was undertaken, with review of case notes and
      immunohistochemical determination of vascular endothelial growth factor (VEGF-A)
      in fibroids. RESULTS: When compared with families with sporadic fibroids,
      familial prevalence of fibroids was associated with a higher incidence of
      abdominal swelling (59.1% versus 41.6%; P=0.037), menorrhagia (84.4% versus
      51.9%; P=0.042), dysmenorrhoea (64.4% versus 46.3%; P=0.004), dyspareunia (43.2%
      versus 27.9%; P=0.012) and family history of cancers (52.3% versus 32.4%;
      P<0.01). The fibroids were also more multiple (mean +/- SEM: 7 +/- 0.86 versus 3
      +/- 0.42; P<0.011) and strong VEGF-A expression in fibroids was more common in
      the familial group (64% versus 28%). Racial distribution was the same in both
      groups (blacks 49%, whites 33.4%, others 18.6%). CONCLUSIONS: Familial prevalence
      of uterine fibroids is associated with distinct clinical and molecular features
      that differ from those found when fibroids occur sporadically in families.

PMID- 15860491
TI  - Predictors of antral follicle count during the reproductive years.
AB  - BACKGROUND: We sought to identify indicators of antral follicle count which would
      be serviceable to clinicians seeking to estimate the number of ovarian follicles
      without relying on sonographic counts. METHODS: We examined the relations of
      chronological age and four potential indicators of ovarian age-ovarian volume,
      FSH, dimeric inhibin B and estradiol-to antral follicle count in 176 recently
      pregnant women. We identified the regression models which best predict low antral
      follicle count (< or =10 follicles). RESULTS: Chronological age, ovarian volume,
      FSH and inhibin B were each significantly associated with antral follicle count.
      Fifty-three (30.1%) women had < or =10 antral follicles. In the total sample, at
      the cutpoint corresponding to 80% sensitivity, the positive predictive value for
      a regression model with all four variables was 60%. All regression models
      performed less well in women <35 years (13.9% with low count) than in women > or
      =35 years (52.0% with low count). In older women, the positive predictive value
      for the model with all four variables was 79%, compared with 60% for a model with
      chronological age alone. CONCLUSIONS: Our models provide a basis for advising
      women aged > or =35 years who are either trying to conceive or wish to learn
      whether they may postpone childbearing.

PMID- 15860492
TI  - Sutureless re-anastomosis by laparoscopy versus microsurgical re-anastomosis by
      laparotomy for sterilization reversal: a matched cohort study.
AB  - BACKGROUND: Sutureless re-anastomosis per laparoscopy is an alternative for
      microsurgical re-anastomosis by laparotomy in the treatment of sterilized women
      with renewed child wish. Our aim was to compare pregnancy rates after both
      surgical techniques. METHODS: We performed a retrospective cohort study in which
      consecutive women who underwent sutureless re-anastomosis per laparoscopy were
      compared to women who underwent microsurgical re-anastomosis by laparotomy. Both
      procedures were performed in neighbouring hospitals in Northern-Brabant, The
      Netherlands, and women were matched for age. The primary outcome was time to
      ongoing pregnancy. RESULTS: Overall, we included 41 women who had sutureless re
      anastomosis by laparoscopy, and 41 age-matched women who underwent microsurgical
      re-anastomosis by laparotomy. The number of women who conceived was 20 (15
      ongoing pregnancies) in the sutureless laparoscopic group versus 26 (24 ongoing
      pregnancies) in the laparotomic group, a difference due to a longer follow-up
      period in the laparotomic group. Time to ongoing pregnancy was comparable in both
      groups (P=0.46), with 3 year cumulative ongoing pregnancy rates of 45 and 52%
      respectively. After adjustment for other prognostic factors, the fecundity rate
      ratio was 0.97 (95% CI 0.26-3.6), indicating a similar performance of the two
      techniques. CONCLUSION: The simplified stitchless laparoscopic procedure for
      reversal of tubal sterilization with the use of a tubal splint, clip fixation of
      the muscularis and fibrin glue resulted in a promising pregnancy rate, which was
      similar to the pregnancy rate obtained with the microsurgical re-anastomosis per
      laparotomy.

PMID- 15860493
TI  - Spindle positions and their distributions in in vivo and in vitro matured mouse
      oocytes.
AB  - BACKGROUND: This study was carried out to compare spindle locations and their
      developmental competencies both in vivo and in vitro in matured mouse oocytes.
      Spindle locations were identified using a polscope. Since meiotic spindles in
      living oocytes are highly birefringent, their structures can be viewed non
      invasively by using a polscope. METHODS: In vivo matured metaphase II oocytes
      were collected from the oviducts of mice. Immature oocytes were collected from
      mouse ovaries, and then cultured in YS medium until the first polar body (PB)
      extrusion. In vitro and in vivo matured oocytes were classified into four
      categories according to their spindle positions relative to the first PB (0
      degrees , 0-90 degrees , 90-180 degrees and without a spindle image), and rates
      of fertilization and blastocyst formation were assessed. In vivo matured oocytes
      with a 0 degrees spindle disposition relative to PB were cultured in vitro for 24
      h, and then their spindle positions were re-assessed. RESULTS: Most in vivo
      matured oocytes (89.1%) had a 0 degrees spindle position. Only 6 and 3% of
      oocytes had spindle positions of 0-90 degrees and 90-180 degrees , respectively.
      No spindle image was observed in 2%. However, most in vitro matured oocytes
      (83.1%) had a 0-90 degrees spindle position and, in contrast, only 6.5% of these
      oocytes had a 0 degrees spindle position. The rate of fertilization and
      blastocyst rate were significantly higher for in vivo matured oocytes than in
      vitro matured oocytes (87.1 versus 64.9% and 76.1% versus 66.0%, respectively,
      P<0.05 for each). We also observed that 71.7% of the in vivo matured oocytes with
      the 0 degrees spindle position showed a spindle position change to 0-90 degrees
      after 24 h of culture. These oocytes had a poor fertilization rate (43%) and a
      zero blastocyst rate. CONCLUSION: In vitro matured mouse oocytes showed quite
      different spindle positions compared with in vivo matured oocytes. Moreover, in
      vivo matured oocytes cultured for 24 h had a spindle position distribution that
      was similar to that of in vitro matured oocytes. The different spindle positions
      observed in in vivo and in vitro matured oocytes may reflect differences in their
      cytoplasmic maturation processes. These findings have implications regarding the
      lower developmental competency of in vitro matured oocytes.

PMID- 15860494
TI  - Expectant management of miscarriage--prediction of outcome using ultrasound and
      novel biochemical markers.
AB  - BACKGROUND: The aim of this study was to examine the value of various ultrasound
      and biochemical parameters for the prediction of successful expectant management
      of miscarriage. METHODS: This was a prospective observational study. Clinically
      stable women with an ultrasound diagnosis of miscarriage were offered expectant
      management. In all cases, gestational age, size of retained products of
      conception, serum HCG, progesterone, 17-hydroxyprogesterone, insulin growth
      factor-binding protein 1 (IGFBP-1), inhibin A and inhibin pro alpha-C RI levels
      were recorded. Follow-up continued until resolution of the pregnancy. Clinical
      data, ultrasound findings and biochemical markers were analysed using univariate
      analysis and decision tree analysis. RESULTS: Fifty-four women underwent
      expectant management of miscarriage. Thirty-seven (69%) had successful expectant
      management and 17 (31%) required surgery. The size of retained products, serum
      HCG, progesterone, inhibin A and inhibin pro alpha-C RI were all significantly
      different in those pregnancies that resolved spontaneously (P<0.05). Serum
      inhibin A was the best predictor of a complete miscarriage. CONCLUSION: This
      study shows that novel biochemical markers may be used to predict the likelihood
      of successful expectant management of miscarriage.

PMID- 15860495
TI  - Higher than expected prevalence of congenital cryptorchidism in Lithuania: a
      study of 1204 boys at birth and 1 year follow-up.
AB  - BACKGROUND: Cryptorchidism at birth is one of the symptoms of testicular
      dysgenesis syndrome (TDS). The aim of the study was to detect prevalence of
      cryptorchidism in Lithuanian newborn boys. METHODS: A total of 1204 consecutively
      born boys were examined within the first days after birth in one regional
      hospital. Boys cryptorchid at birth were reexamined 1 year later. RESULTS: The
      prevalence of cryptorchidism at birth was 5.7% (69 cases). Cryptorchidism was
      associated with low birth weight (P < 0.0001), preterm delivery (P < 0.0001),
      small gestational weight (P = 0.03) and other congenital abnormalities of
      genitalia (P = 0.0001). No correlation between cryptorchidism at birth and
      maternal age, birth order or mode of delivery was demonstrated in this study, but
      paternal body mass index <20 kg/m2 was found to be a significant risk factor (P =
      0.001). The prevalence of congenital cryptorchidism at 1 year of age was 1.4%.
      CONCLUSIONS: We detected lower frequency of cryptorchidism at birth in Lithuanian
      boys than in Danes (9.0%), but higher than in Finns (2.4%). We had expected the
      frequencies in Lithuania and Finland to be relatively similar because the other
      symptoms of TDS (incidence of testicular cancer and semen quality) are close in
      these countries.

PMID- 15860496
TI  - Seminal haploid cell detection by flow cytometry in non-obstructive azoospermia:
      a good predictive parameter for testicular sperm extraction.
AB  - BACKGROUND: Testicular sperm extraction (TESE) associated with ICSI gives
      patients suffering from non-obstructive azoospermia (NOA) the possibility of
      becoming a father. The success rate of TESE based on sperm recovery is
      approximately 50%, and the commonly used non-invasive parameters are not
      predictive enough. Only the invasive testis biopsy has a good prognostic value.
      The aim of this study was to evaluate the prognostic value of the detection of
      seminal haploid cells by flow cytometry (FCM) in order to avoid unnecessary
      testicular biopsy. METHODS: For 37 NOA patients undergoing testicular biopsy, we
      measured testis size, serum FSH and inhibin B levels and carried out seminal
      cytology, seminal FCM analysis and histological examination. RESULTS: Sperm were
      found in 18 biopsies. These results were correlated with cytology, FCM analysis
      and the histological examination. FCM was more sensitive than cytology (100
      versus 59%) but less specific (67 versus 83.5%) whereas the histological
      observation of complete spermatogenesis appeared to be less sensitive (50%) but
      more specific (100%). CONCLUSION: Detection of seminal haploid cells by FCM
      appears to be an interesting non-invasive technique which can predict TESE
      results and improve the management of NOA patients.

PMID- 15860497
TI  - Exposure to persistent organochlorine pollutants associates with human sperm Y:X
      chromosome ratio.
AB  - BACKGROUND: During the last decades, there has been concern that exposure to
      endocrine disruptors, such as persistent organochlorine pollutants (POPs), may
      contribute to sex ratio changes in offspring of exposed populations. METHODS: To
      investigate whether exposure to 2,2'4,4'5,5'-hexachlorobiphenyl (CB-153) and
      dichlorodiphenyl dichloroethene (p,p'-DDE) affect Y:X chromosome proportion,
      semen of 149 Swedish fishermen, aged 27-67 years, was investigated. The men
      provided semen and blood for analysis of hormone, CB-153 and p,p'-DDE levels. The
      proportion of Y- and X-chromosome bearing sperm in semen samples was determined
      by two-colour fluorescence in situ hybridization (FISH) analysis. RESULTS: Log
      transformed CB-153 as well as log transformed p,p'-DDE variables were both
      significantly positively associated with Y chromosome fractions (P-values = 0.05
      and <0.001, respectively). Neither age, smoking nor hormone levels showed any
      association with Y-chromosome fractions. CONCLUSIONS: This is the first study to
      indicate that exposure to POPs may increase the proportion of ejaculated Y
      bearing spermatozoa. These data add to the growing body of evidence that exposure
      to POPs may alter the offspring sex ratio.

PMID- 15860498
TI  - Laparoscopic stripping of endometriomas: a randomized trial on different surgical
      techniques. Part II: pathological results.
AB  - BACKGROUND: The stripping technique for endometriomas excision has been reported
      to be associated with follicular loss. The objective of this trial was to
      evaluate the presence and nature of ovarian tissue adjacent to the endometrioma
      cyst wall obtained by stripping with different techniques. METHODS: Forty-eight
      patients with ovarian endometrioma were enrolled in two consecutive independent
      randomized trials. Two different techniques were analysed at the initial adhesion
      site (circular excision and subsequent stripping versus immediate stripping). Two
      different techniques were analysed at the ovarian hilus (stripping versus
      coagulation and cutting). Histology analysis was performed in three portions of
      the cyst wall (initial adhesion site, intermediate part of the specimen, ovarian
      hilus). RESULTS: Recognizable ovarian tissue was inadvertently excised together
      with the endometrioma cyst wall in most cases. At initial adhesion sites more
      ovarian tissue was removed with the circular excision technique (< 0.001). No
      significant difference in quality of ovarian tissue (number and type of
      follicles) was found between specimens obtained with different surgical
      techniques at the initial or at the final part of the procedure. At the initial
      adhesion site and at the intermediate part of the cyst wall, the ovarian tissue
      removed along with the endometrioma wall was mainly constituted by tissue with no
      follicles or only primordial follicles (60% and 48% of the specimens from the
      initial part with both techniques, and from the intermediate part, respectively,
      had no follicles or only primordial follicles). Close to the ovarian hilus the
      ovarian tissue removed along with the endometrioma wall mostly consisted of
      tissue which contained primary and secondary follicles (69% of the cases,
      combining the two groups). CONCLUSIONS: Ovarian tissue is inadvertently excised
      together with the endometrioma wall in most cases. The excised tissue is at
      normal functional development stages only near the ovarian hilus. The different
      techniques used do not influence significantly the quality of the resected
      tissue.

PMID- 15860499
TI  - Association between sequence variations in genes encoding human zona pellucida
      glycoproteins and fertilization failure in IVF.
AB  - BACKGROUND: The zona pellucida (ZP) has multiple roles in reproductive processes,
      including oocyte maturation, fertilization and implantation. We used, for the
      first time, a genetic approach to study whether human ZP genes possess structural
      alterations in women with unsuccessful IVF trials. In theory, this may result in
      gradual reduction of sperm-zona interaction and eventually in total fertilization
      failure (TFF). METHODS: Eighteen infertile women (TFFs) whose IVF did not result
      in any fertilized oocytes, whereas fertilization by ICSI was successful, were
      screened for mutations in ZP genes by means of conformation-sensitive gel
      electrophoresis. Twenty-three fertilizers in IVF (FIVFs) and 68 women with proven
      fertility (WPFs) constituted the two control groups. RESULTS: Altogether, 20
      sequence variations were found in the ZP genes. Two variations in ZP3, one in the
      regulatory region (c. 1-87 T --> G) and one in exon 6 [c. 894 G --> A (p. K298)]
      existed more frequently in TFFs than in FIVF and WPF groups (P-values 0.027 and
      0.008, respectively). CONCLUSIONS: Our study on ZP genes of infertile women
      revealed a high degree of sequence variations. This may reflect gradual reduction
      of fertility among TFFs, but the putative roles and influences of single
      variations can only be hypothesized.

PMID- 15860500
TI  - Rates of suppression and recovery of human sperm output in testosterone-based
      hormonal contraceptive regimens.
AB  - BACKGROUND: Practical hormonal male contraceptive regimens are likely to have
      delayed onset and offset of reliable contraception dictated by the length of the
      spermatogenic cycle and clearance rate of pre-formed sperm from the ductular
      system. While delayed onset of contraceptive efficacy is an accepted feature of
      vasectomy, reliable time estimates for a hormonal male contraceptive of time to
      onset and offset of reliable contraception and of resumption of normal male
      fertility are required. METHODS AND RESULTS: We utilized the sperm output data
      from three male contraceptive efficacy studies to define quantitative estimates
      of suppression and recovery rates from an androgen alone (testosterone enanthate)
      and an androgen/progestin (testosterone/depot medroxyprogesterone acetate) study.
      Using nearly 14,000 semen samples from World Health Organization (WHO) studies
      #85921 and #89903 with identical protocols, the rate of suppression of sperm
      output was best modelled as a two-parameter, single exponential decay function
      with effective half-time to suppression of 5.5 weeks and times of 6.8 weeks to 10
      x 10(6)/ml, 8.7 weeks to 5 x 10(6)/ml, 10.0 weeks to 3 x 10(6)/ml and 13.0 weeks
      to 1 x 10(6)/ml. The rate of recovery using absolute sperm concentration was best
      modelled as a three-parameter, sigmoidal curve with effective time to reach half
      of the recovery plateau of 10.5 weeks and times of 9.0 weeks to 3 x 10(6)/ml, 9.9
      weeks to 5 x 10(6)/ml, 11.5 weeks to 10 x 10(6)/ml, and 13.6 weeks to 20 x
      10(6)/ml. Using relative sperm output, defined as a percentage of the
      participants' own baseline, recovery approached an asymptotic plateau of
      approximately 85% of geometric mean pre-treatment sperm concentration. In the
      combination androgen/progestin study, suppression rate was significantly faster
      (effective time to reach half maximal suppression of 3.0 weeks) and recovery
      significantly slower (effective time to reach half of recovery plateau of 14.7
      weeks) and less complete (asymptotic recovery plateau of 43% of baseline) than in
      the androgen-alone WHO studies. CONCLUSION: These findings therefore provide
      large sample estimates of the suppression and recovery rates from an androgen
      alone hormonal male contraceptive regimen as a basis for comparison with other
      second-generation combination androgen/progestin regimens that are the most
      promising approach to developing practical male hormonal regimens.

PMID- 15860501
TI  - GnRH agonist versus GnRH antagonist in oocyte donation cycles: a prospective
      randomized study.
AB  - BACKGROUND: The specific role of LH in folliculogenesis and oocyte maturation is
      unclear. GnRH antagonists, when administered in the late follicular phase, induce
      a sharp decrease in serum LH which may be detrimental for IVF outcome. This study
      was performed to evaluate whether the replacement of GnRH agonist (triptorelin)
      by a GnRH antagonist (ganirelix; NV Organon) in oocyte donation cycles has any
      impact on pregnancy and implantation rates. METHODS: A total of 148 donor IVF
      cycles was randomly assigned to use either a GnRH antagonist daily administered
      from the 8th day of stimulation (group I) or a GnRH agonist long protocol (group
      II) for the ovarian stimulation of their donors. The primary endpoints were the
      pregnancy and the implantation rates. RESULTS: The clinical pregnancy rate per
      transfer (39.72%, 29/73 versus 41.33%, 31/75) based on transvaginal scan findings
      at 7 weeks of gestation, the implantation rate (23.9 versus 25.4%) and the first
      trimester abortion rate (10.34 versus 12.90%) were similar in the two groups.
      CONCLUSION: In oocyte donation cycles the replacement of GnRH agonist by a GnRH
      antagonist appears to have no impact on the pregnancy and implantation rates when
      its administration starts on day 8 of stimulation.

PMID- 15860502
TI  - An improved mechanical technique for assisted hatching.
AB  - BACKGROUND: Varied clinical outcomes of assisted hatching (AH) have been
      reported. We attempt to investigate whether the size of the zona opening created
      by AH is adequate for blastocyst hatching, and, if not, set up a new method to
      improve it. METHODS: A new AH technique, long zona dissection (LZD), was
      established, and experiments were performed to compare the effects of different
      sizes of zona opening on complete hatching of blastocysts in mouse and human
      embryos in vitro. RESULTS: The LZD technique can create a long zona slit on early
      embryos, even blastocysts, with the slit size beyond two-thirds of zona diameter.
      Compared with three-dimensional partial zona dissection, LZD can significantly
      enhance the hatching speed and the rate of complete hatching of mouse blastocysts
      (93.9%). All (100%) human blastocysts completely hatched following LZD; however,
      when the slit size after AH was about two-fifths of zona diameter, more of the
      larger inner cell masses (ICM) became trapped by the zona opening during hatching
      than the smaller ICM (53.3 versus 12.5%, P = 0.01). CONCLUSIONS: Zona opening of
      moderate size following AH is inadequate for the completion of blastocyst
      hatching in vitro; in some cases, however, it can be significantly improved by
      LZD.

PMID- 15860503
TI  - Optimizing cryopreservation of human testicular tissue: comparison of protocols
      with glycerol, propanediol and dimethylsulphoxide as cryoprotectants.
AB  - BACKGROUND: Cryopreservation of testicular tissue is an option in fertility
      preservation for pre-pubertal boys who will lose spermatogenic cells as a result
      of chemotherapy. We compared three different protocols and cryoprotectants in
      cryopreservation of testicular tissue. METHODS: Testicular tissue obtained from
      16 infertile men was evaluated by light microscopy(LM), immunostaining against
      MAGE-A4, transmission electron microscopy (TEM) and organ culture. Seminiferous
      tubules (1312) from non-frozen (n = 16) and frozen-thawed samples (n = 34) were
      studied following cryopreservation using protocols with either 1,2-propanediol
      (PrOH), glycerol or dimethylsulphoxide (DMSO) as cryoprotectants. RESULTS: Normal
      structure was seen in 86 +/- 6% (mean +/- SD) of the fresh tissue. After freezing
      with DMSO, 70 +/- 6% and after PrOH, 37+/-3% of the tubules were judged to be
      good. When glycerol was used, the structure of the basal compartment of the
      tubules was severely damaged. The ultrastructure of the cryopreserved samples as
      revealed by TEM and MAGE-positive spermatogonia confirmed the findings.
      Cryopreserved Leydig cells maintained their morphology and ability to release
      testosterone in culture. CONCLUSION: DMSO as a cryoprotectant (at a 0.7 mol/l
      concentration) proved to maintain the structure of testicular tissue, especially
      spermatogonia, after cryopreservation better than PrOH or glycerol.

PMID- 15860504
TI  - A bias in genotyping the ERBB2 (HER2) Ile655Val variant.

PMID- 15860505
TI  - Effectors of mammalian telomere dysfunction: a comparative transcriptome analysis
      using mouse models.
AB  - Critical telomere shortening in the absence of telomerase in late generation Terc
      /- mice (G3 Terc-/-) or loss of telomere capping due to abrogation of the DNA
      repair/telomere binding protein Ku86 (Ku86-/- mice) results in telomere
      dysfunction and organismal premature aging. Here, we report on genome-wide
      transcription in mouse G3 Terc-/-, Ku86-/- and G3 Terc-/-/Ku86-/- germ cells
      using high-density oligonucleotide microarrays. Although a few transcripts are
      modulated specifically in Ku86- or Terc-deficient cells, the observed
      transcriptional response is mainly inductive and qualitatively similar for all
      three genotypes, with highest transcriptional induction observed in double mutant
      G3 Terc-/-/Ku86-/- cells compared with either single mutant. Analysis of 92 known
      genes induced in G3 Terc-/-/Ku86-/- germ cells compared with wild-type cells
      shows predominance of genes involved in cell adhesion, cell-to-cell and cell-to
      matrix communication, as well as increased metabolic turnover and augmented
      antioxidant responses. In addition, the data presented in this study support the
      view that telomere dysfunction induces a robust compensatory response to rescue
      impaired germ cell function through the induction of survival signals related to
      the PI3-kinase pathway, as well as by the coordinated upregulation of transcripts
      that are essential for mammalian spermatogenesis.

PMID- 15860506
TI  - The initiation of colon cancer in a chronic inflammatory setting.
AB  - Chronic inflammation predisposes to cancer. We used an inflammation-induced human
      model of tumorigenesis to explore how populations of mutated cells expand and
      initiate the earliest stages of cancer. Ulcerative colitis (UC) is a chronic
      inflammatory disease of the colon associated with an increased risk of colorectal
      cancer mediated through a process of genomic instability. In order to
      characterize the process of clonal expansion, arbitrary primed (AR) and inter
      simple sequence repeat (ISSR) PCR DNA fingerprint mutation profiles of single
      crypts were compared with the mutational profiles from clusters of crypts and
      whole biopsies within the same individual. To provide information at the earliest
      steps of neoplastic progression, we examined histologically negative crypts, as
      well as dysplastic crypts. Crypts from UC dysplasia/cancer show alterations in 10
      20% of DNA fingerprint sites, regardless of (i) whether the crypts were
      dysplastic or non-dysplastic and (ii) whether the DNA came from one crypt or
      thousands of crypts. Of the mutational changes in single crypts, almost half are
      clonally expanded to adjacent crypts and/or to the thousands of crypts in a
      single biopsy. Using fluorescent in-situ hybridization to examine p53 alterations
      in individual crypt cells, we demonstrate that the mechanism of clonal expansion
      can occur through crypt fission. DNA alterations are initiated in colonic crypts
      and expand to adjacent crypts through crypt fission. Our data suggest that a
      continuous process of DNA mutations, clonal expansion through crypt fission and
      clonal succession initiates the development of inflammatory-associated colon
      cancer; this mutational process is moderated by crypt cell turn-over and cell
      death. This paradigm may apply to other inflammatory-induced cancers.

PMID- 15860507
TI  - (-)-Epigallocatechin-3-gallate promotes pro-matrix metalloproteinase-7 production
      via activation of the JNK1/2 pathway in HT-29 human colorectal cancer cells.
AB  - Matrix metalloproteinase (MMP)-7 (matrilysin-1) plays significant roles in the
      growth, invasion, and metastasis of colorectal tumors, while (-)-epigallocatechin
      3-gallate (EGCG), a green tea polyphenol with chemopreventive properties, has
      been shown to be an inhibitor of MMP-2 and MMP-9. In the present study, HT-29
      human colorectal cancer cells were treated with EGCG to examine its effects on
      pro-MMP-7 induction and production using RT-PCR and western blot analyses.
      Surprisingly, EGCG (10-100 microM) treatment increased both intracellular and
      extracellular pro-MMP-7 protein levels (2.6-8.4-fold and 1.9-6.4-fold,
      respectively) in dose- and time-dependent manner, with a significant upregulation
      of its mRNA expression. EGCG also activated extracellular signal-regulated
      protein kinase (ERK)1/2, c-JUN NH2-terminal kinase (JNK)1/2 and p38 mitogen
      activated protein kinase (MAPK), as previously reported. In addition, the
      polyphenol triggered the phosphorylation of c-JUN (Ser63 and Ser73) and induced c
      JUN/c-FOS, thereby increasing the DNA binding activity of activator protein-1 (AP
      1), as shown by an AP-1 luciferase reporter assay. Pharmacological blockade of
      MAPK activities suggested that pro-MMP-7 expression was induced via JNK1/2
      activation, but not in the case of ERK1/2 or p38 MAPK. N-Acetyl-L-cysteine,
      superoxide (O2-) dismutase and catalase attenuated the EGCG-induced pro-MMP-7
      production, suggesting an involvement of oxidative stress in these events.
      Conversely, EGCG spontaneously generated O2- in a cell-free system that utilized
      a cytochrome C reduction method. Further, (-)-epicatechin-3-gallate (25 and 100
      microM) and green tea polyphenols (33 and 132 microg/ml) induced pro-MMP-7
      expression, whereas (-)-epicatechin and (-)-epigallocatechin (100 microM each)
      did not. Induction of pro-MMP-7 expression by EGCG was also shown in another
      human colorectal adenocarcinoma cell line, Caco-2. Our results suggest that some
      green tea catechins induce pro-MMP-7 production via O2- production and the
      activation of JNK1/2, c-JUN, c-FOS and AP-1 in HT-29 cells.

PMID- 15860509
TI  - Comparison of different definitions to classify remission and sustained
      remission: 1 year TEMPO results.
AB  - OBJECTIVE: To assess methods to calculate achieving and sustaining remission in a
      double blind randomised trial in patients with RA who received etanercept,
      methotrexate, or an etanercept/methotrexate combination. METHODS: Remission was
      defined as DAS <1.6, DAS28 <2.6, and ACR70 response. Sustaining remission was
      analysed in three ways: (a) analysis of sustained DAS remission, DAS28 remission,
      or ACR70 response continuously for 6 months; (b) analysis of sustained remission
      appraised through a continuity rewarded scoring system, which is the weighted sum
      of all intervals in the study in which patients are in DAS or DAS28 remission; or
      (c) longitudinal modelling of remission odds using generalised estimating
      equations. RESULTS: Significantly more patients treated with the
      etanercept/methotrexate combination reached DAS remission (37%) than those
      treated with either methotrexate (14%) or etanercept (18%) alone (p<0.01).
      Results for DAS28 and for the ACR70 response were similar. Agreement between DAS
      remission and DAS28 remission was good, but agreement between either of these and
      the ACR70 response was less. Patients in DAS or DAS28 remission had a lower level
      of disease activity (fewer active joints, lower ESR) than those achieving ACR70
      response; the converse was seen using pain VAS. The three methods were comparable
      for sustainability of remission and showed significant advantage for combination
      therapy, which increased the number and durability of remission periods.
      CONCLUSIONS: DAS and DAS28 remission results were similar for assessing achieving
      and sustaining remission in RA, frequently differing from patients classified as
      ACR70 responders. The three methods of examining duration of remission produced
      comparable results.

PMID- 15860508
TI  - Tamoxifen resistance and Her2/neu expression in an aged, irradiated rat breast
      carcinoma model.
AB  - Clear links have been established between occupational or therapeutic radiation
      exposure and breast cancer. Tamoxifen chemoprevention following radiation
      exposure may be able to reduce the risk of developing breast cancer later in
      life. In order to model carcinogenesis in this setting, an in vivo model of
      tamoxifen chemoprevention and tamoxifen failure in a radiation-induced rat
      mammary carcinoma model was characterized. Two hundred and twenty-seven 60-day
      old female rats received whole body or sham exposure to ionizing radiation.
      Thirty days later long-term, continuous, tamoxifen chemoprevention was initiated
      in half the population and all animals were monitored over three and a half years
      for the development of mammary tumors. Mammary tumors were surgically removed and
      carcinomas were histologically identified and characterized. Results showed that
      tamoxifen chemoprevention decreased the incidence and prolonged the latency of
      radiation-induced mammary carcinomas. However, many individuals receiving
      tamoxifen chemoprevention developed their first carcinoma very late in life.
      These carcinomas shared morphological features distinct from the majority of
      carcinomas that developed in the absence of tamoxifen chemoprevention. Analyses
      of cell lines established from these carcinomas and immunohistochemistry of tumor
      sections revealed that the highest levels of Her2/neu expression were associated
      with in vivo tamoxifen exposure. Treatment of rat mammary carcinoma cells with an
      anti-rat Her2/neu monoclonal antibody (MAb 7.16.4) inhibited cell growth and this
      effect was more pronounced in the presence of tamoxifen. These studies suggest
      that carcinoma growth driven by the Her2/neu pathway may be associated with
      tamoxifen chemoprevention failure in the rat mammary carcinoma model.
      Additionally, strategies combining targeted Her2/neu antibodies, vaccines or
      drugs with estrogen pathway modification may be more effective in reducing breast
      cancer chemoprevention failures.

PMID- 15860510
TI  - Productivity costs among patients with rheumatoid arthritis: the influence of
      methods and sources to value loss of productivity.
AB  - OBJECTIVE: To assess productivity costs incurred by rheumatoid arthritis,
      comprising paid as well as household productivity costs, from a societal
      perspective, using different methods. METHODS: A questionnaire on productivity,
      including items of the Health and Labour Questionnaire, was completed by 576
      patients with rheumatoid arthritis (mean disease duration seven years). The
      friction cost (FC) method using the gross national wage per hour was applied to
      estimate paid productivity, and the market equivalent was used to value loss of
      household productivity. Sensitivity analyses to estimate paid productivity costs
      among patients of working age included the human capital (HC) method and an
      alternative source, namely the "added value", to value loss of paid productivity.
      RESULTS: In the total study population, mean (SD) annual costs from loss of paid
      productivity according to the FC method were estimated to be 278 (1,559) and mean
      annual household productivity costs were 2,045 (3,882). When using the HC method,
      mean annual costs increased to an average of 4,434 (9,957). When using the added
      value of production, average FC costs increased from 455 to 540 among patients of
      working age. CONCLUSIONS: Costs from loss of household productivity in rheumatoid
      arthritis were seven times higher than costs from loss of paid productivity,
      assessed by the FC method. The high paid productivity costs when using the HC
      method reflect the high work disability rate in rheumatoid arthritis. As the
      method of measuring and source of valuing productivity loss has an important
      influence on the costs, a consensus to standardise these issues is desirable.

PMID- 15860511
TI  - Combination treatment strategies in early rheumatoid arthritis.
AB  - Combinations of disease modifying antirheumatic drugs (DMARDs) are increasingly
      being used in patients with early rheumatoid arthritis (RA) when long term
      results with sequential DMARD monotherapy are disappointing. Combination DMARD
      therapy may be more effective than monotherapy, and has no additional short term
      adverse events. The evidence for using combination DMARD therapy is still weak,
      however, and further trials are needed.

PMID- 15860512
TI  - Tumour necrosis factor receptor gene therapy affects cellular immune responses in
      collagen induced arthritis in mice.
AB  - BACKGROUND: Collagen induced arthritis (CIA) is an animal model of rheumatoid
      arthritis (RA) amenable to immunotherapy directed against tumour necrosis factor
      alpha (TNFalpha). OBJECTIVE: To evaluate whether local TNF receptor (TNF-R) gene
      therapy in DBA/1 mice exerts an influence beyond anti-inflammatory effects. Two
      measures of CIA pathogenesis were investigated-namely, immunity to collagen II
      (CII) 245-270 peptide (the major immunodominant epitope within bovine CII) and
      the preferential activation of T cell Vbeta8.2 variable region receptors in
      arthritic DBA/1 mice. METHODS: DBA/1 mice received single periarticular
      injections of media or retroviral vectors containing LacZ or human TNF-R into
      affected arthritic paws at disease onset. Disease severity was monitored, immune
      responses towards the immunodominant bovine CII 245-270 and subdominant CII 334
      360 peptide epitopes were assessed by ELISA, and T cell Vbeta usage was analysed
      by real time polymerase chain reaction for the LacZ transduced, TNF-R, and viral
      free media treated control animals. The therapeutic influence of TNF-R gene
      transduction was compared with other groups at different times after treatment.
      RESULTS: Reduced disease severity was seen 15-35 days after treatment, with a
      concomitant increase in immunity towards the subdominant CII 334-360 peptide
      epitope rather than the immunodominant CII 245-270 peptide in TNF-R treated
      animals. Early in the disease, TNF-R treated animals demonstrated a reduction of
      bias towards the otherwise predominant Vbeta8.2 T cell subset. CONCLUSIONS: TNF-R
      gene therapy influences cellular immunity in CIA, leading to overall disease
      amelioration, thus suggesting that TNF inhibition may have therapeutic potential
      beyond the control of inflammation in RA.

PMID- 15860513
TI  - Diagnostic accuracy of a 2D left ventricle hypertrophy score for familial
      hypertrophic cardiomyopathy.
AB  - AIMS: To study the diagnostic value of a new 2D left ventricle hypertrophy (2D
      LVH) score in families with hypertrophic cardiomyopathy (HCM) in comparison with
      the conventional maximal wall thickness (MWT) measurement (>13 mm in adults),
      which is limited by a low sensitivity in relatives. METHODS AND RESULTS: The
      study was performed in 237 adults from genotyped families with HCM. Population A
      (derivation sample) comprised 109 adults and population B (validation sample)
      comprised 128 adults. MWT and 2D LVH scores (sum of thicknesses of four segments)
      were determined by echocardiography. Genotyping was the gold standard for
      diagnosis. In population A, a theoretical value for LVH score was determined in
      the healthy population by a multiple linear regression model including age, sex,
      and body surface area. An abnormal cut-off value was defined as an LVH score
      above a maximum theoretical value according to receiver operating characteristic
      analysis. Sensitivity and specificity were, respectively, 73 and 96% for 2D LVH
      score and 62.5 and 100% for MWT. Improvement of sensitivity was particularly
      important in adults <50 years of age (69 vs. 54%, respectively, P<0.04). These
      results were validated in population B: sensitivity and specificity of LVH score
      were, respectively, 75 and 96% in this sample and 67 and 97%, in the subgroup <50
      years. In the latter, sensitivity of LVH score increased when compared with that
      of MWT (67 vs. 53%, P<0.03). CONCLUSIONS: The LVH score has a higher diagnostic
      value for HCM than the conventional criterion of MWT, particularly in young
      adults. This echographic parameter may be proposed as an alternative diagnostic
      criterion for familial screening.

PMID- 15860514
TI  - Getting to the heart of obesity.

PMID- 15860515
TI  - Menopausal complaints, oestrogens, and heart disease risk: an explanation for
      discrepant findings on the benefits of post-menopausal hormone therapy.
AB  - There is a large discrepancy between the findings of observational and
      experimental studies on the effects of post-menopausal hormone therapy (HT) and
      coronary heart disease risk. Observational studies, mainly comprising peri
      menopausal women, report risk reductions up to 30-50%, whereas the experimental
      studies, comprising elderly women, do not show coronary protection. Suggested
      explanations are methodological differences, such as confounding or healthy user
      bias, incomplete capture of early events, the stage of atherosclerosis at the
      start of HT, formulation or dose of HT, or early susceptibility to thrombotic
      events. We propose that the presence of climacteric complaints determines the
      susceptibility to hormone replacement therapy. Climacteric complaints are the
      main indication for HT in the population, whereas in the clinical trials women
      with climacteric complaints were either explicitly excluded or comprised only a
      minority of the total randomized population. There is some, albeit circumstantial
      evidence to support this hypothesis. Women with climacteric complaints of
      sweating not only appear to have lower levels of serum oestradiol, but also lose
      more bone than women without climacteric complaints. Consequently, sweating
      episodes may indicate potential benefits from HT. It has also been reported that
      hot flushes during menopause correlate with a higher level of oxidative stress
      and an increased cardiovascular reactivity to stressful situations. We suggest
      epidemiological approaches to test our hypothesis.

PMID- 15860516
TI  - Unrecognized heart failure in elderly patients with stable chronic obstructive
      pulmonary disease.
AB  - AIMS: To establish the prevalence of unrecognized heart failure in elderly
      patients with a diagnosis of chronic obstructive pulmonary disease, in a stable
      phase of their disease. METHODS AND RESULTS: In a cross-sectional study, patients
      >/=65 years of age, classified as having chronic obstructive pulmonary disease by
      their general practitioner and not known with a cardiologist-confirmed diagnosis
      of heart failure, were invited to our out-patient clinic. Four hundred and five
      participants underwent an extensive diagnostic work-up, including medical history
      and physical examination, followed by chest radiography, electrocardiography,
      echocardiography, and pulmonary function tests. As reference (i.e. 'gold')
      standard the consensus opinion of an expert panel was used. The panel based the
      diagnosis of heart failure on all available results from the diagnostic
      assessment, guided by the diagnostic principles of the European Society of
      Cardiology (ESC) for heart failure (i.e., symptoms and echocardiographic systolic
      and/or diastolic dysfunction). The diagnosis of chronic obstructive pulmonary
      disease was based on the diagnostic criteria of the Global Initiative (GOLD) for
      chronic obstructive pulmonary disease. Of 405 participating patients with a
      diagnosis of chronic obstructive pulmonary disease, 83 (20.5%, 95% CI 16.7-24.8)
      had previously unrecognized heart failure (42 patients systolic, 41 'isolated'
      diastolic, and none right-sided heart failure). In total, 244 (60.2%) patients
      had chronic obstructive pulmonary disease according to the GOLD criteria and 50
      (20.5%, 95% CI 15.6-26.1) patients combined with unrecognized heart failure.
      CONCLUSION: Unrecognized heart failure is very common in elderly patients with
      stable chronic obstructive pulmonary disease. Closer co-operation among general
      practitioners, pulmonologists, and cardiologists is necessary to improve
      detection and adequate treatment of heart failure in this large patient
      population.

PMID- 15860517
TI  - Left ventricular hypertrophy in aortic valve stenosis: preventive or promotive of
      systolic dysfunction and heart failure?
AB  - AIMS: In aortic stenosis (AS), left ventricular (LV) hypertrophy is considered a
      compensatory response helping maintain systolic function. Recent research in
      experimental AS suggests, however, that LV hypertrophy is not necessary to
      sustain LV contractions but may in fact be maladaptive. The present work aimed to
      clarify the role of LV hypertrophy in AS-related heart failure (HF) in man.
      METHODS AND RESULTS: We studied 137 adult patients with isolated AS undergoing
      pre-operative echocardiography and cardiac catheterization. HF was diagnosed by
      the European criteria and LV hypertrophy by sex-specific limits of
      echocardiographic LV mass. The higher the LV mass was, the poorer was the LV
      ejection fraction (beta=-0.26, P< 0.001, linear regression) and the greater the
      likelihood of HF independent of the severity of AS (P< 0.001, logistic
      regression). In the subgroup of critical AS (valve area <0.4 cm(2)/m(2), n=85),
      patients with absent LV hypertrophy (n=19) had better preserved ejection fraction
      (mean+/-SE, 64+/-3 vs. 57+/-2%, P=0.045) and less HF (16 vs. 48%, P=0.025) than
      patients with LV hypertrophy (n=66). CONCLUSION: In isolated AS, increased LV
      mass predicts the presence of systolic dysfunction and HF independent of the
      severity of valvular obstruction. LV hypertrophy may be maladaptive rather than
      beneficial in AS in man.

PMID- 15860518
TI  - Use of granulocyte-colony stimulating factor during acute myocardial infarction
      to enhance bone marrow stem cell mobilization in humans: clinical and
      angiographic safety profile.
AB  - AIMS: There is increasing evidence that stem cell (SC) mobilization to the heart
      and their differentiation into cardiac cells is a naturally occurring process. We
      sought to assess the safety and feasibility of granulocyte-colony stimulating
      factor (G-CSF) administration in humans to enhance SC mobilization and left
      ventricle (LV) injury repair during myocardial infarction (MI). METHODS AND
      RESULTS: Twenty patients with STEMI (mean age, 61+/-10 years), of whom 14 were
      submitted to primary percutaneous coronary intervention, were randomized to G-CSF
      (5 microg/kg/day s.c. for 4 consecutive days) or placebo. At entry and then at
      months 3 and 6, (99m)Tc-sestamibi gated-SPECT was performed to estimate extension
      of perfusion defect (PD) and LV function. The study drug was well tolerated and
      induced a significant increase of white blood count, CD34(+) cells, and CD34(+)
      cells coexpressing AC133 and VEGFR-2. At follow-up, treated and placebo groups
      did not differ for the angiographic coronary late loss and showed a similar
      pattern of PD recovery, whereas in the former at 6 months LVEF and especially
      LVEDV tended to be relatively higher (P=0.068) and lower (P=0.054), respectively.
      CONCLUSION: G-CSF administration in acute MI patients was feasible and did not
      lead to any clinical or angiographic adverse events and resulted in CD34(+) and
      CD34(+)AC133(+)VEGFR2(+) cell mobilization.

PMID- 15860519
TI  - Five year clinical effect of coronary stenting and coronary artery bypass
      grafting in renal insufficient patients with multivessel coronary artery disease:
      insights from ARTS trial.
AB  - AIMS: To compare coronary stent implantation and bypass surgery for multivessel
      coronary disease in patients with renal insufficiency. METHODS AND RESULTS: In
      the ARTS trial, 142 moderate renal insufficient patients (Ccr<60 mL/min) with
      multivessel coronary disease were randomly assigned to stent implantation (n=69)
      or CABG (n=73). At 5 years, there was no significant difference between the two
      groups in terms of mortality (14.5% in the stent group vs. 12.3% in the CABG
      group, P=0.81), or combined endpoint of death, cerebrovascular accident (CVA), or
      myocardial infarction (MI) (30.4% in the stent group vs. 23.3% in the CABG group,
      P=0.35). Among patients who survived without CVA or MI, 18.8% in the stent group
      underwent a second revascularization procedure when compared with 8.2% in the
      surgery group (P=0.08). The event-free survival at 5 years was 50.7% in the stent
      group and 68.5% in the surgery group (P=0.04). CONCLUSION: At 5 years, the
      differences in mortality and combined incidence of death, CVA, and MI between
      coronary stenting and surgery did not reach statistically significant level.
      However, the occurrence of MACCE in the stent group was higher than in the CABG
      group, mainly driven by the higher incidence of repeat revascularization in the
      stent group.

PMID- 15860520
TI  - Elevation of asymmetric dimethylarginine in patients with unstable angina and
      recurrent cardiovascular events.
AB  - AIMS: We investigated the role of asymmetric dimethylarginine (ADMA) for clinical
      outcome of patients with unstable angina. METHODS AND RESULTS: Forty-five
      patients with stable angina, 36 patients with unstable angina, and 40 healthy
      controls were included in this study. Coronary artery disease (CAD) patients were
      prospectively followed for 1 year. ADMA levels were measured at baseline and
      after 6 weeks using a validated ELISA. Baseline ADMA concentration in controls
      was significantly lower than in patients with CAD (0.59+/-0.23 vs. 0.76+/-0.17
      micromol/L; P<0.001). Patients with unstable angina had significantly higher
      baseline ADMA levels than patients with stable angina (0.82+/-0.18 vs. 0.73+/
      0.15 micromol/L; P=0.01). There was a significant reduction of ADMA levels at 6
      weeks after percutaneous coronary intervention (PCI) in patients with unstable
      angina who experienced no recurrent cardiovascular event (from 0.81+/-0.14 to
      0.73+/-0.19 micromol/L; P<0.05). In contrast, patients with unstable angina who
      had an event showed no significant decrease in ADMA at 6 weeks. Actuarial
      survival analysis showed a significantly higher event rate in patients with
      persistently elevated ADMA plasma concentrations. CONCLUSION: ADMA is
      significantly elevated in patients with unstable angina. A reduced ADMA level at
      6 weeks after PCI may indicate a decreased risk of recurrent cardiovascular
      events.

PMID- 15860521
TI  - The effect of perindopril on cardiovascular morbidity and mortality in patients
      with diabetes in the EUROPA study: results from the PERSUADE substudy.
AB  - AIMS: The aim of this study was to assess the effect of the angiotensin
      converting enzyme inhibitor perindopril on cardiovascular events in diabetic
      patients with coronary artery disease. METHODS AND RESULTS: A total of 1502
      diabetic patients with known coronary artery disease and without heart failure of
      12 218 overall in the EUropean trial on Reduction Of cardiac events with
      Perindopril in stable coronary Artery (EUROPA) disease were randomized in a
      double-blinded manner to perindopril 8 mg once daily or placebo. Follow-up was
      for a median of 4.3 years. The primary end point was cardiovascular death, non
      fatal myocardial infarction, and resuscitated cardiac arrest. Perindopril
      treatment was associated with a non-significant reduction in the primary endpoint
      in the diabetic population, 12.6 vs. 15.5%, relative risk reduction 19% [(95% CI,
      -7 to 38%), P=0.13]. This was of similar relative magnitude to the 20% risk
      reduction observed in the main EUROPA population. CONCLUSION: Perindopril tends
      to reduce major cardiovascular events in diabetic patients with coronary disease
      in addition to other preventive treatments and the trend towards reduction was of
      a similar relative magnitude to that observed the general population with
      coronary artery disease.

PMID- 15860522
TI  - Inositide evolution - towards turtle domination?
AB  - When viewing the changes in our understanding of inositides over the last 20
      years, it is difficult to know whether to be more impressed by the proliferation
      in the number of inositides themselves (e.g. seven polyphosphoinositol lipids,
      more than 30 inositol phosphates), or by the number of functions for each. This
      review will focus on two specific aspects of this diversity: the evolution of the
      polyphosphoinositides, and the synthesis and functions of the higher inositol
      phosphates.

PMID- 15860523
TI  - Facilitatory effect of Ins(1,4,5)P3 on store-operated Ca2+-permeable cation
      channels in rabbit portal vein myocytes.
AB  - In rabbit portal vein smooth muscle cells, store-operated Ca2+-permeable cation
      channels (SOCs) display multi-modal gating mechanisms. SOCs are activated by
      depletion of intracellular Ca2+ stores but also may be stimulated in a store
      independent manner by noradrenaline acting on alpha-adrenoceptors and by
      diacylglycerol (DAG) via protein kinase C (PKC). In the present study we have
      investigated whether inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) modulates SOC
      activity in freshly dispersed rabbit portal vein myocytes with patch pipette
      recording techniques. Inclusion of 1 mum Ins(1,4,5)P3 in the patch pipette
      solution increased whole-cell currents evoked by the Ca2+-ATPase inhibitor
      cyclopiazonic acid (CPA) by about 3-fold at -80 mV. In the cell-attached
      configuration the cell-permeable Ca2+ chelator BAPTA-AM stimulated SOC activity
      and after excision of an isolated inside-out patch bath application of 1 mum
      Ins(1,4,5)P3 increased open channel probability (NP(o)) by approximately 3-fold.
      Ins(1,4,5)P3 also produced a similar increase in NP(o) of SOCs stimulated by the
      phorbol ester, phorbol 12,13-dibutyrate (PDBu) in inside-out patches and these
      channel currents had a unitary conductance of about 2 pS. The equilibrium
      constant of Ins(1,4,5)P3 on increasing PDBu-evoked SOC activity was about 0.4
      mum. The facilitatory effect of Ins(1,4,5)P3 was also manifest as markedly
      increasing the rate of activation of SOCs. The synergistic effect of Ins(1,4,5)P3
      was mimicked by the metabolically stable analogue 3-fluoro-Ins(1,4,5)P3 and
      Ins(1,4)P2, a metabolite of Ins(1,4,5)P3, but was not inhibited by the classical
      Ins(1,4,5)P3 receptor antagonist heparin. Finally Ins(1,4,5)P3 also increased
      NP(o) of SOCs activated by a PKC catalytic subunit. It is concluded that
      Ins(1,4,5)P3 facilitates SOC opening via a heparin-insensitive mechanism at, or
      close to, the channel protein.

PMID- 15860524
TI  - Increase in group II excitation from ankle muscles to thigh motoneurones during
      human standing.
AB  - In standing subjects, we investigated the excitation of quadriceps (Q)
      motoneurones by muscle afferents from tibialis anterior (TA) and the excitation
      of semitendinosus (ST) motoneurones by muscle afferents from gastrocnemius
      medialis (GM). Standing with a backward lean stretches the anterior muscle pair
      (TA and Q) and they must be co-contracted to maintain balance. Equally, forward
      lean stretches the posterior muscle pair (GM and ST) and they must be co
      contracted. We used these conditions of enhanced lean to increase the influence
      of gamma static motoneurones on muscle spindle afferents, which enhances the
      background input from these afferents to extrafusal motoneurones. The effects of
      the conditioning volleys on motoneurone excitability was estimated using the
      modulation of the on-going rectified EMG and of the H reflex. Stimulation of
      afferents from TA in the deep peroneal nerve at 1.5-2 x MT (motor threshold)
      evoked early group I and late group II excitation of Q motoneurones. Stimulation
      of afferents in the GM nerve at 1.3-1.8 MT evoked only late group II excitation
      of ST motoneurones. The late excitation produced by the group II afferents was
      significantly greater when subjects were standing and leaning than when they
      voluntarily co-contracted the same muscle pairs at the same levels of activation.
      The early effect produced by the group I afferents was unchanged. We propose that
      this increase in excitation by group II afferents reflects a posture-related
      withdrawal of a tonic inhibition that is exerted by descending noradrenergic
      control and is specific to the synaptic actions of group II afferents.

PMID- 15860525
TI  - Role of chloride channels in bradykinin-induced guinea pig airway vagal C-fibre
      activation.
AB  - We tested the hypothesis that an ionic current carried by chloride ions
      contributes to bradykinin (BK)-induced membrane depolarization and activation of
      vagal afferent C-fibres. In an ex vivo innervated trachea/bronchus preparation,
      BK (1 microM) consistently produced action potential discharge in vagal afferent
      C-fibres with receptive fields in the trachea or main stem bronchus. The Ca2+
      activated Cl- channel (CLCA) inhibitor, niflumic acid (NFA, 100 microM),
      significantly reduced BK-induced action potential discharge to 21 +/- 7% of the
      control BK response. NFA did not inhibit capsaicin-induced or citric-acid-induced
      action potential discharge in tracheal C-fibres. The inhibitory effect of NFA was
      mimicked by another CLCA inhibitor, 5-nitro-2-(3-phenylpropylamino)-benzoic acid
      (NPPB, 100 microM). NFA also inhibited the BK-induced inward current in
      gramicidin-perforated whole-cell patch-clamp recordings of capsaicin-sensitive
      jugular ganglion neurones retrogradely labelled from the airways. NFA did not
      inhibit the BK-induced increase in intracellular free Ca2+. The TRPV1 inhibitor,
      iodo-resiniferatoxin (1 microM), also partially inhibited BK-induced action
      potential discharge, and the combination of iodo-resiniferatoxin and NFA
      virtually abolished the BK-induced action potential discharge. We concluded that
      in vagal afferent C-fibres, BK evokes membrane depolarization and action
      potential discharge through the additive effects of TRPV1 and Cl- channel
      activation.

PMID- 15860526
TI  - A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in
      mouse pancreatic beta cells.
AB  - The blood glucose-lowering hormone glucagon-like peptide-1 (GLP-1) stimulates
      cAMP production, promotes Ca2+ influx, and mobilizes an intracellular source of
      Ca2+ in pancreatic beta cells. Here we provide evidence that these actions of GLP
      1 are functionally related: they reflect a process of Ca2+-induced Ca2+ release
      (CICR) that requires activation of protein kinase A (PKA) and the Epac family of
      cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs). In rat insulin
      secreting INS-1 cells or mouse beta cells loaded with caged Ca2+ (NP-EGTA), a GLP
      1 receptor agonist (exendin-4) is demonstrated to sensitize intracellular Ca2+
      release channels to stimulatory effects of cytosolic Ca2+, thereby allowing CICR
      to be generated by the uncaging of Ca2+ (UV flash photolysis). This sensitizing
      action of exendin-4 is diminished by an inhibitor of PKA (H-89) or by
      overexpression of dominant negative Epac. It is reproduced by cell-permeant cAMP
      analogues that activate PKA (6-Bnz-cAMP) or Epac (8-pCPT-2'-O-Me-cAMP)
      selectively. Depletion of Ca2+ stores with thapsigargin abolishes CICR, while
      inhibitors of Ca2+ release channels (ryanodine and heparin) attenuate CICR in an
      additive manner. Because the uncaging of Ca2+ fails to stimulate CICR in the
      absence of cAMP-elevating agents, it is concluded that there exists in beta cells
      a process of second messenger coincidence detection, whereby intracellular Ca2+
      release channels (ryanodine receptors, inositol 1,4,5-trisphosphate (IP3)
      receptors) monitor a simultaneous increase of cAMP and Ca2+ concentrations. We
      propose that second messenger coincidence detection of this type may explain how
      GLP-1 interacts with beta cell glucose metabolism to stimulate insulin secretion.

PMID- 15860527
TI  - Clathrin-mediated endocytosis in snake motor terminals is directly facilitated by
      intracellular Ca2+.
AB  - At the snake neuromuscular junction, low temperature (LT, 5-7 degrees C) blocks
      clathrin-mediated endocytosis (CME) while exocytosis is largely unaffected. Thus
      compensatory endocytosis that normally follows transmitter release is inhibited,
      or 'delayed' until the preparation is warmed to room temperature (RT). This delay
      was exploited to observe how changes in bulk [Ca(2+)](i) directly affect CME.
      Motor terminals were loaded with fura-2 to monitor [Ca(2+)](i). With brief
      stimulation at LT, [Ca(2+)](i) transiently increased but returned to baseline (
      approximately 63 nm) in < 8 min. After 15 min at LT, [Ca(2+)](i) was altered by
      incubating preparations in the Ca(2+) ionophore ionomyocin. Preparations were
      then warmed to RT to initiate delayed endocytosis, which was quantified as uptake
      of the fluorescent optical probe sulforhodamine 101. Endocytosis was more rapid
      when [Ca(2+)](i) increased; the rate at 300 nm Ca(2+) was approximately double
      that under basal conditions. Thus the rate of CME - isolated from stimulation,
      transmitter release, and other forms of endocytosis - is directly influenced by
      intraterminal Ca(2+).

PMID- 15860528
TI  - Biophysical and pharmacological characterization of nicotinic cholinergic
      receptors in rat cochlear inner hair cells.
AB  - Before the onset of hearing, a transient efferent innervation is found on inner
      hair cells (IHCs). This synapse is inhibitory and mediated by a nicotinic
      cholinergic receptor (nAChR) probably formed by the alpha9 and alpha10 subunits.
      We analysed the pharmacological and biophysical characteristics of the native
      nAChR using whole-cell recordings from IHCs in acutely excised apical turns of
      the rat organ of Corti. Nicotine did not activate but rather blocked the
      acetylcholine (ACh)-evoked currents with an IC50 of 1 +/- 0.1 microM. Antagonists
      of non-cholinergic receptors such as strychnine, bicuculline and ICS-205930
      blocked ACh-evoked responses with an IC50 of 8.6 +/- 0.8 nM, 59 +/- 4 nM and 0.30
      +/- 0.02 microM, respectively. The IHC nAChR was both permeable to (P(Ca)/P(Na) =
      8 +/- 0.9) and modulated by external Ca2+. ACh-evoked currents were potentiated
      by Ca2+ up to 500 microM but were reduced by higher concentrations of this
      cation. Ba2+ mimicked the effects of Ca2+ whereas Mg2+ only blocked these
      currents. In addition, elevation of extracellular Ca2+ reduced the amplitude of
      spontaneous synaptic currents without affecting their time course. The receptor
      had an EC50 for ACh of 60.7 +/- 2.8 microM in 0.5 mM Ca2+. In the absence of
      Ca2+, the EC50 for ACh increased, suggesting that potentiation by Ca2+ involves
      changes in the apparent affinity for the agonist. These pharmacological and
      biophysical characteristics of the IHC nAChR closely resemble those of the
      recombinant alpha9alpha10 nAChR, reinforcing the hypothesis that the functional
      nAChR at the olivocochlear efferent-IHC synapse is composed of both the alpha9
      and alpha10 subunits.

PMID- 15860529
TI  - Metabolic alkalosis reduces exercise-induced acidosis and potassium accumulation
      in human skeletal muscle interstitium.
AB  - Skeletal muscle releases potassium during activity. Interstitial potassium
      accumulation is important for muscle function and the development of fatigue
      resulting from exercise. In the present study we used sodium citrate ingestion as
      a tool to investigate the relationship between interstitial H+ concentration and
      K+ accumulation during exercise. Seven healthy subjects performed one-legged knee
      extensor exercise on two separate days with and without sodium citrate ingestion.
      Interstitial H+ and K+ concentrations were measured with the microdialysis
      technique. Citrate ingestion reduced the plasma H+ concentration and increased
      the plasma HCO3- concentration. Citrate had no effect on interstitial H+ at rest.
      The increase in interstitial H+ concentration during intense exercise was
      significantly lower (P < 0.05) with citrate ingestion compared to control (peak
      interstitial H+ concentration 79 versus 131 nM). After 3 min of exercise
      interstitial K+ concentration was reduced (P < 0.05) in the citrate (alkalosis)
      compared to the control experiment (8.0 +/- 0.9 versus 11.0 +/- 2 mM) and
      interstitial K+ concentration remained lower during the rest of the exercise
      period. The present study demonstrated a link between interstitial H+ and K+
      accumulation, which may be through the ATP-sensitive K+ channels (KATP channels),
      which are sensitive to changes in H+.

PMID- 15860530
TI  - Reduced alpha-adrenoceptor responsiveness and enhanced baroreflex sensitivity in
      Cry-deficient mice lacking a biological clock.
AB  - To reveal the role of clock genes in generating the circadian rhythm of
      baroreflexes, we continuously measured mean arterial pressure and baroreflex
      sensitivity in free-moving normal wild-type mice, and in Cry-deficient mice which
      lack a circadian rhythm, in constant darkness for 24 h. In wild-type mice the
      mean arterial pressure was higher at night than during the day, and was
      accompanied by a significantly enhanced baroreflex sensitivity of -13.6 +/- 0.8
      at night compared with -9.7 +/- 0.7 beats min(-1) mmHg(-1) during the day (P <
      0.001). On the other hand, diurnal changes in arterial pressure disappeared in
      Cry-deficient mice with remarkably enhanced baroreflex sensitivity compared with
      wild-type mice (P < 0.001): -21.9 +/- 1.6 at night and -23.1 +/- 2.1 beats min(
      1) mmHg(-1) during the day. Moreover, the mean arterial pressure response to 10
      microg kg(-1) of phenylephrine, an alpha1-adrenoceptor agonist, was severely
      suppressed in Cry-deficient mice regardless of time, while that for the wild-type
      mice was 10.1 +/- 1.9 mmHg in the night, significantly lower than 22.0 +/- 3.5
      mmHg in the day (P < 0.01). These results suggest that CRY genes are involved in
      generating the circadian rhythm of baroreflex sensitivity, partially by
      regulating alpha(1)-adrenoceptor-mediated vasoconstriction in peripheral vessels.

PMID- 15860531
TI  - Cerebrovascular responses to hypoxia and hypocapnia in high-altitude dwellers.
AB  - Cerebral blood flow is known to increase in response to hypoxia and to decrease
      with hypocapnia. It is not known, however, whether these responses are altered in
      high-altitude dwellers who are not only chronically hypoxic and hypocapnic, but
      also polycythaemic. Here we examined cerebral blood flow responses to hypoxia and
      hypocapnia, separately and together, in Andean high-altitude dwellers, including
      some with chronic mountain sickness (CMS), which is characterized by excessive
      polycythaemia. Studies were carried out at high altitude (Cerro de Pasco (CP),
      Peru; barometric pressure (P(B)) 450 mmHg) and repeated, following relief of the
      hypoxia, on the day following arrival at sea level (Lima, Peru; P(B) 755 mmHg).
      We compared these results with those from eight sea-level residents studied at
      sea level. In nine high-altitude normal subjects (HA) and nine CMS patients, we
      recorded middle cerebral artery mean blood flow velocity (MCAVm) using
      transcranial Doppler ultrasonography, and expressed responses as changes from
      baseline. MCAVm responses to hypoxia were determined by changing end-tidal
      partial pressure of oxygen (P(ET,O2)) from 100 to 50 mmHg, with end-tidal partial
      pressure of carbon dioxide clamped. MCAVm responses to hypocapnia were studied by
      voluntary hyperventilation with (P(ET,O2)) clamped at 100 and 50 mmHg. There were
      no significant differences between the cerebrovascular responses of the two
      groups to any of the interventions at either location. In both groups, the MCAVm
      responses to hypoxia were significantly greater at Lima than at CP (HA, 12.1 +/-
      1.3 and 6.1 +/- 1.0%; CMS, 12.5 +/- 0.8 and 5.6 +/- 1.2%; P < 0.01 both groups).
      The responses at Lima were similar to those in the sea-level subjects (13.6 +/-
      2.3%). The responses to normoxic hypocapnia in the altitude subjects were also
      similar at both locations and greater than those in sea-level residents. During
      hypoxia, both high-altitude groups showed responses to hypocapnia that were
      significantly smaller at Lima than at CP (HA, 2.17 +/- 0.23 and 3.29 +/- 0.34%
      mmHg(-1), P < 0.05; CMS, 1.87 +/- 0.16 and 3.23 +/- 0.24% mmHg(-1); P < 0.01).
      The similarity of the results from the two groups of altitude dwellers suggests
      that haematocrit is unlikely to greatly affect cerebrovascular reactivity to
      hypoxia and hypocapnia. The smaller vasodilatation to hypoxia and larger
      vasoconstriction to hypoxic hypocapnia at high altitude suggest that
      cerebrovascular responses may be impaired at the high altitude, i.e. a
      maladaptation. The changes in the responses within less than 24 h at sea level
      indicate that this impairment is rapidly reversible.

PMID- 15860532
TI  - Sex differences in transgenerational alterations of growth and metabolism in
      progeny (F2) of female offspring (F1) of rats fed a low protein diet during
      pregnancy and lactation.
AB  - Compelling epidemiological and experimental evidence indicates that a suboptimal
      environment during fetal and neonatal development in both humans and animals may
      programme offspring susceptibility to later development of several chronic
      diseases including obesity and diabetes in which altered carbohydrate metabolism
      plays a central role. One of the most interesting and significant features of
      developmental programming is the evidence from several studies that the adverse
      consequences of altered intrauterine environments can be passed
      transgenerationally from mother (F0) to daughter (F1) to second generation
      offspring (F2). We determined whether when F0 female rats are exposed to protein
      restriction during pregnancy and/or lactation their F1 female pups deliver F2
      offspring with in vivo evidence of altered glucose and insulin metabolism. We fed
      F0 virgin Wistar rats a normal control 20% casein diet (C) or a protein
      restricted isocaloric diet (R) containing 10% casein during pregnancy. F1 female
      R pups weighed less than C at birth. After delivery, mothers received C or R diet
      during lactation to provide four F1 offspring groups CC (first letter pregnancy
      diet and second lactation diet), RR, CR and RC. All F1 female offspring were fed
      ad libitum with C diet after weaning and during their first pregnancy and
      lactation. As they grew female offspring (F1) of RR and CR mothers exhibited low
      body weight and food intake with increased sensitivity to insulin during a
      glucose tolerance test at 110 days of postnatal life. Male F2 CR offspring showed
      evidence of insulin resistance. In contrast RC F2 females showed evidence of
      insulin resistance. Sex differences were also observed in F2 offspring in resting
      glucose and insulin and insulin: glucose ratios. These sex differences also
      showed differences specific to stage of development time window. We conclude that
      maternal protein restriction adversely affects glucose and insulin metabolism of
      male and female F2 offspring in a manner specific to sex and developmental time
      window during their mother's (the F1) fetal and neonatal development.

PMID- 15860533
TI  - Limitations to systemic and locomotor limb muscle oxygen delivery and uptake
      during maximal exercise in humans.
AB  - Reductions in systemic and locomotor limb muscle blood flow and O2 delivery limit
      aerobic capacity in humans. To examine whether O2 delivery limits both aerobic
      power and capacity, we first measured systemic haemodynamics, O2 transport and O2
      uptake during incremental and constant (372 +/- 11 W; 85% of peak power; mean +/-
      S.E.M.) cycling exercise to exhaustion (n = 8) and then measured systemic and leg
      haemodynamics and during incremental cycling and knee-extensor exercise in male
      subjects (n = 10). During incremental cycling, cardiac output and systemic O2
      delivery increased linearly to 80% of peak power (r2 = 0.998, P < 0.001) and then
      plateaued in parallel to a decline in stroke volume (SV) and an increase in
      central venous and mean arterial pressures (P < 0.05). In contrast, heart rate
      and increased linearly until exhaustion (r2 = 0.993; P < 0.001) accompanying a
      rise in systemic O2 extraction to 84 +/- 2%. In the exercising legs, blood flow
      and O2 delivery levelled off at 73-88% of peak power, blunting leg per unit of
      work despite increasing O2 extraction. When blood flow increased linearly during
      one-legged knee-extensor exercise, per unit of work was unaltered on fatigue.
      During constant cycling, , SV, systemic O2 delivery and reached maximal values
      within approximately 5 min, but dropped before exhaustion (P < 0.05) despite
      increasing or stable central venous and mean arterial pressures. In both types of
      maximal cycling, the impaired systemic O2 delivery was due to the decline or
      plateau in because arterial O2 content continued to increase. These results
      indicate that an inability of the circulatory system to sustain a linear increase
      in O2 delivery to the locomotor muscles restrains aerobic power. The similar
      impairment in SV and O2 delivery during incremental and constant load cycling
      provides evidence for a central limitation to aerobic power and capacity in
      humans.

PMID- 15860534
TI  - Calcitonin gene-related peptide antagonism attenuates the haemodynamic and
      glycaemic responses to acute hypoxaemia in the late gestation sheep fetus.
AB  - The fetal defence to acute hypoxaemia involves cardiovascular and metabolic
      responses, which include peripheral vasoconstriction and hyperglycaemia. Both
      these responses are mediated via neuroendocrine mechanisms, which require the
      stimulation of the sympathetic nervous system. In the adult, accumulating
      evidence supports a role for calcitonin gene-related peptide (CGRP) in the
      activation of sympathetic outflow. However, the role of CGRP in stimulated
      cardiovascular and metabolic functions before birth is completely unknown. This
      study tested the hypothesis that CGRP plays a role in the fetal cardiovascular
      and metabolic defence responses to acute hypoxaemia by affecting sympathetic
      outflow. Under anaesthesia, five sheep fetuses at 0.8 of gestation were
      surgically instrumented with catheters and a femoral arterial Transonic flow
      probe. Five days later, fetuses were subjected to 0.5 h hypoxaemia during either
      i.v. saline or a selective CGRP antagonist in randomised order. Treatment started
      30 min before hypoxaemia and ran continuously until the end of the challenge.
      Arterial samples were taken for blood gases, metabolic status and hormone
      analyses. CGRP antagonism did not alter basal arterial blood gas, metabolic,
      cardiovascular or endocrine status. During hypoxaemia, similar falls in Pa,O2
      occurred in all fetuses. During saline infusion, hypoxaemia induced hypertension,
      bradycardia, femoral vasoconstriction, hyperglycaemia and an increase in
      haemoglobin, catecholamines and neuropeptide Y (NPY). In contrast, CGRP
      antagonism markedly diminished the femoral vasoconstrictor and glycaemic
      responses to hypoxaemia, and attenuated the increases in haemoglobin,
      catecholamines and NPY. Combined, these results strongly support the hypothesis
      that CGRP plays a role in the fetal cardiovascular and metabolic defence to
      hypoxaemia by affecting sympathetic outflow.

PMID- 15860535
TI  - Onset exercise hyperaemia in humans: partitioning the contributors.
AB  - Using a step-wise, reductionist approach we characterized the time course and
      degree to which mechanical, vasodilatory and cardiac mechanisms contribute to the
      increase in leg blood flow (LBF) at the onset of dynamic knee-extensor exercise.
      Heart rate (HR) and LBF (ultrasound Doppler) were evaluated during (1) voluntary
      and (2) passive exercise in the seated position, (3) passive exercise in the
      supine position with the leg above the heart, and (4) passive exercise with
      measurements made in the non-moving leg. In trials 2 and 3, the degree of change
      and time course of peak DeltaHR (8.7 +/- 2 bpm, seated; 10 +/- 1 bpm, supine) and
      peak DeltaLBF (518 +/- 135 ml min(-1), seated; 448 +/- 179 ml min(-1), supine)
      were similar, supporting the concept that the skeletal muscle pump was minimized.
      Even with the reduction of skeletal muscle pump and metabolic influences (trials
      2, 3 and 4) a significant cardio-acceleration and hyperaemia was seen. In the
      first 5 s of seated passive exercise, the retrograde component of the blood
      velocity profile was significantly greater than rest or the 5-20 s interval,
      which may suggest an arterial inflow that initially exceeded leg vasodilatation.
      Steady-state LBF (minutes 2 and 3) remained elevated during voluntary exercise,
      but returned to near baseline during passive movement. Taken together, these data
      suggest that cardio-acceleration (i.e. tachycardia) and mechanical forces other
      than the skeletal muscle pump play a role in reducing vascular resistance and
      ultimately increasing LBF at the onset of exercise, followed by steady-state LBF
      which matches muscle metabolic demand.

PMID- 15860536
TI  - Spectrally opponent inputs to the human luminance pathway: slow +L and -M cone
      inputs revealed by low to moderate long-wavelength adaptation.
AB  - The luminance pathway has slow (s), spectrally opponent cone inputs in addition
      to the expected fast (f), non-opponent inputs. The nature of these inputs to
      luminance flicker perception was further explored psychophysically by measuring
      middle- (M-) and long-wavelength-sensitive (L-) cone modulation sensitivities, M-
      and L-cone phase delays, and flicker spectral sensitivities under three
      conditions of low to moderate long-wavelength adaptation. Under these conditions
      we find that the luminance channel has fast M- and L-cone input signals (+fM and
      +fL), and slow, spectrally opponent cone input signals (+sL and -sM). The slow
      signals found under these conditions are therefore of the opposite polarity to
      those (+sM and -sL) found under more intense long-wavelength adaptation. At these
      less intense levels, fast and slow M-cone signals of opposite polarity (-sM and
      +fM) cancel at low frequencies, but then constructively interfere at intermediate
      frequencies (ca 12.5-22.5 Hz, depending on adapting level) because of the delay
      between them. In contrast, fast and slow L-cone signals of the same polarity (+sL
      and +fL) sum at low frequencies, but then destructively interfere at intermediate
      frequencies. Importantly, the spectrally opponent signals (+sL and -sM)
      contribute to flicker nulls without producing visible colour variation. Although
      its output generates an achromatic percept, the luminance channel has slow
      spectrally opponent as well as fast non-opponent inputs.

PMID- 15860537
TI  - Spectrally opponent inputs to the human luminance pathway: slow +M and -L cone
      inputs revealed by intense long-wavelength adaptation.
AB  - The nature of the inputs to achromatic luminance flicker perception was explored
      psychophysically by measuring middle- (M-) and long-wavelength-sensitive (L-)
      cone modulation sensitivities, M- and L-cone phase delays, and spectral
      sensitivities as a function of temporal frequency. Under intense long-wavelength
      adaptation, the existence of multiple luminance inputs was revealed by
      substantial frequency-dependent changes in all three types of measure. Fast (f)
      and slow (s) M-cone input signals of the same polarity (+sM and +fM) sum at low
      frequencies, but then destructively interfere near 16 Hz because of the delay
      between them. In contrast, fast and slow L-cone input signals of opposite
      polarity (-sL and +fL) cancel at low frequencies, but then constructively
      interfere near 16 Hz. Although these slow, spectrally opponent luminance inputs
      (+sM and -sL) would usually be characterized as chromatic, and the fast, non
      opponent inputs (+fM and +fL) as achromatic, both contribute to flicker
      photometric nulls without producing visible colour variation. Although its output
      produces an achromatic percept, the luminance channel has slow, spectrally
      opponent inputs in addition to the expected non-opponent ones. Consequently, it
      is not possible in general to silence this channel with pairs of 'equiluminant'
      alternating stimuli, since stimuli equated for the non-opponent luminance
      mechanism (+fM and +fL) may still generate spectrally opponent signals (+sM and
      +sL).

PMID- 15860538
TI  - Estimated neutron dose to embryo and foetus during commercial flight.
AB  - A study has been carried out to assess the radiation exposure from cosmic-ray
      neutrons to the embryo and foetus of pregnant aircrew and air travellers in
      consideration of the radiation exposure from cosmic-ray neutrons to the embryo
      and foetus. A Monte Carlo analysis was performed to determine the equivalent dose
      from neutrons to the brain and body of an embryo at 8 weeks and to the foetus at
      the 3, 6 and 9 month periods. Neutron fluence-to-absorbed dose conversion
      coefficients for the foetal brain and for the entire foetal body (isotropic
      irradiation geometry) have been determined at the four developmental stages. The
      equivalent dose rate to the foetus during commercial flights has been further
      evaluated considering the fluence-to-absorbed dose conversion coefficients, a
      neutron spectrum measured at an altitude of 11.3 km and an ICRP-92 radiation
      weighting factor for neutrons. This study indicates that the foetus can exceed
      the annual dose limit of 1 mSv for the general public after, for example, 15
      round trips on commercial trans-Atlantic flights.

PMID- 15860539
TI  - Chemical composition of 14C in airborne release from the Tokai reprocessing
      plant, Japan.
AB  - Fuel reprocessing plant is one of the most important sources of anthropogenic
      (14)C in the environment. A method was developed to determine the amount and
      chemical composition of airborne (14)C release from the Tokai reprocessing plant,
      Japan. Effluent monitoring using this method showed most of the (14)C is released
      in CO(2) form and the ratio of (14)C in hydrocarbons to the total is less than
      3%, not depending on the type of fuel reprocessed. This finding would provide
      improved understanding on dynamical behaviour of (14)C in the environment and
      assessment of radioecological impact from nuclear fuel cycle.

PMID- 15860540
TI  - Determination of natural radioactivity in building materials used in Tunisian
      dwellings by gamma ray spectrometry.
AB  - The radioisotopic content of 17 samples of natural and manufactured building
      materials collected in Tunisia have been analysed by using gamma spectrometry.
      From the measured gamma ray spectra, activity concentrations are determined for
      (232)Th, (226)Ra, (235)U and (40)K. The total effective dose and the activity
      concentration index are calculated applying the dose criteria recommended by the
      European Union for building materials. The results of (226)Ra, (232)Th and (40)K
      found in Tunisian building materials indicate that radium and thorium
      concentrations do not exceed 40 Bq kg(-1), but potassium concentration varies
      between 50 and 1215 Bq kg(-1). The total effective dose rates per person indoors
      are determined to be between 0.07 and 0.86 mSv y(-1). Only two materials exceed
      the reference level of 0.3 mSv y(-1). The activity concentration index is <1.

PMID- 15860541
TI  - Role of tissue kallikrein in the cardioprotective effects of ischemic and
      pharmacological preconditioning in myocardial ischemia.
AB  - Tissue kallikrein (TK), a major kinin-forming enzyme, is synthesized in the heart
      and arteries. We tested the hypothesis that TK plays a protective role in
      myocardial ischemia by performing ischemia-reperfusion (IR) injury, with and
      without ischemic preconditioning (IPC) or ACE inhibitor (ramiprilat)
      pretreatment, in vivo in littermate wild-type (WT) or TK-deficient (TK-/-) mice.
      IR induced similar infarcts in WT and TK-/-. IPC reduced infarct size by 65% in
      WT, and by 40% in TK-/- (P<0.05, TK-/- vs WT). Ramiprilat also reduced infarct
      size by 29% in WT, but in TK-/- its effect was completely suppressed.
      Pretreatment of WT with a B2, but not a B1, kinin receptor antagonist reproduced
      the effects of TK deficiency. However, B2 receptor-deficient mice (B2-/-)
      unexpectedly responded to IPC or ramiprilat like WT mice. But pretreatment of the
      B2-/- mice with a B1 antagonist suppressed the cardioprotective effects of IPC
      and ramiprilat. In B2-/-, B1 receptor gene expression was constitutively high. In
      WT and TK-/- mice, both B2 and B1 mRNA levels increased several fold during IR,
      and even more during IPC+IR. Thus TK and the B2 receptor play a critical role in
      the cardioprotection afforded by two experimental maneuvers of potential clinical
      relevance, IPC and ACE inhibition, during ischemia.

PMID- 15860542
TI  - Robust modeling in screening studies: estimation of sensitivity and preclinical
      sojourn time distribution.
AB  - In early-detection clinical trials, quantities such as the sensitivity of the
      screening modality and the preclinical duration of the disease are important to
      describe the natural history of the disease and its interaction with a screening
      program. Assume that the schedule of a screening program is periodic and that the
      sojourn time in the preclinical state has a piecewise density function. Modeling
      the preclinical sojourn time distribution as a piecewise density function results
      in robust estimation of the distribution function. Our aim is to estimate the
      piecewise density function and the examination sensitivity using both generalized
      least squares and maximum likelihood methods. We carried out extensive
      simulations to evaluate the performance of the methods of estimation. The
      different estimation methods provide complimentary tools to obtain the unknown
      parameters. The methods are applied to three breast cancer early-detection
      trials.

PMID- 15860543
TI  - Optimal design and efficiency of two-phase case-control studies with error-prone
      and error-free exposure measures.
AB  - This paper addresses optimal design and efficiency of two-phase (2P) case-control
      studies in which the first phase uses an error-prone exposure measure, Z, while
      the second phase measures true, dichotomous exposure, X, in a subset of subjects.
      Optimal design of a separate second phase, to be added to a preexisting study, is
      also investigated. Differential misclassification is assumed throughout. Results
      are also applicable to 2P cohort studies with error-prone and error-free measures
      of disease status but error-free exposure measures. While software based on the
      mean score method of Reilly and Pepe (1995, Biometrika 82, 299--314) can find
      optimal designs given pilot data, the lack of simple formulae makes it difficult
      to generalize about efficiency compared to one-phase (1P) studies based on X
      alone. Here, formulae for the optimal ratios of cases to controls and first- to
      second-phase sizes, and the optimal second-phase stratified sampling fractions,
      given a fixed budget, are given. The maximum efficiency of 2P designs compared to
      a 1P design is deduced and is shown to be bounded from above by a function of the
      sensitivities and specificities of Z. The efficiency of 'balanced' separate
      second-phase designs (Breslow and Cain, 1988, Biometrika 75, 11--20)-in which
      equal numbers of subjects are chosen from each first-phase strata-compared to
      optimal design is deduced, enabling situations where balanced designs are nearly
      optimal to be identified.

PMID- 15860544
TI  - Lung cancer rate predictions using generalized additive models.
AB  - Predictions of lung cancer incidence and mortality are necessary for planning
      public health programs and clinical services. It is proposed that generalized
      additive models (GAMs) are practical for cancer rate prediction. Smooth
      equivalents for classical age-period, age-cohort, and age-period-cohort models
      are available using one-dimensional smoothing splines. We also propose using two
      dimensional smoothing splines for age and period. Variance estimation can be
      based on the bootstrap. To assess predictive performance, we compared the models
      with a Bayesian age-period-cohort model. Model comparison used cross-validation
      and measures of predictive performance for recent predictions. The models were
      applied to data from the World Health Organization Mortality Database for females
      in five countries. Model choice between the age-period-cohort models and the two
      dimensional models was equivocal with respect to cross-validation, while the two
      dimensional GAMs had very good predictive performance. The Bayesian model
      performed poorly due to imprecise predictions and the assumption of linearity
      outside of observed data. In summary, the two-dimensional GAM performed well. The
      GAMs make the important prediction that female lung cancer rates in these
      countries will be stable or begin to decline in the future.

PMID- 15860545
TI  - Endogenous CCAAT/enhancer binding protein beta and p300 are both regulated by
      growth hormone to mediate transcriptional activation.
AB  - The regulation of c-fos transcription by GH involves multiple factors, including
      CCAAT/enhancer binding protein (C/EBP) beta. Knockdown of C/EBPbeta by RNA
      interference prevents stimulation of endogenous c-fos mRNA by GH, indicating a
      key role for C/EBPbeta in GH-stimulated c-fos transcription. GH rapidly increases
      the occupancy of both endogenous C/EBPbeta and p300 on the c-fos promoter in 3T3
      F442A preadipocytes as indicated by chromatin immunoprecipitation. The transient
      occupancy of p300 on c-fos and the presence of p300 in the anti-C/EBPbeta
      immunoprecipitate coincide with the transient increase in c-fos transcription
      with GH, suggesting that a nuclear complex containing both p300 and C/EBPbeta
      occupies the c-fos promoter in response to GH. Expression of p300 with C/EBPbeta
      markedly increases c-fos promoter activity when neither alone is effective,
      indicating that p300 coactivates C/EBPbeta-mediated c-fos promoter activation.
      Such coactivation can determine a baseline for c-fos activation by GH.
      Furthermore, the occupancy of phosphorylated murine C/EBPbeta (T188) on c-fos
      upon GH treatment is simultaneous with increased occupancy by p300, suggesting
      that phospho-C/EBPbeta recruits p300 in response to GH. Thus, endogenous
      C/EBPbeta and p300 on c-fos are dynamically regulated by GH to determine
      transcriptional activation. Phosphorylated C/EBPbeta and p300 appear to function
      as part of a regulated complex that mediates GH-stimulated transcription.

PMID- 15860546
TI  - Female steroid hormones use signal transducers and activators of transcription
      protein-mediated pathways to modulate the expression of T-bet in epithelial
      cells: a mechanism for local immune regulation in the human reproductive tract.
AB  - The transcription factor T-bet promotes the differentiation of inflammatory Th1 T
      helper cells. T-bet expression in lymphoid cells is regulated by cytoplasmic
      signaling through Janus kinase phosphorylation, nuclear signaling using signal
      transducers and activators of transcription (Stat) family proteins, and
      autocrine/paracrine feedback involving interferon (IFN)-gamma. T-bet is here
      shown to be present in epithelial cells of the human female reproductive tract.
      Regulation of T-bet expression was modulated by cytokines and the female
      reproductive steroids, estrogen, and progesterone. The mechanisms of T-bet
      regulation in epithelia differ from those in conventional immune cells. During a
      15-d exposure to progesterone, T-bet levels in endometrial epithelial cells
      (EECs) undulated. Prior exposure to estrogen enhanced these effects. More
      prolonged exposure of EECs to these hormones, singly or in combination,
      suppressed T-bet production. Stat1 and Stat5 bound to the EEC T-bet regulatory
      region (TRR) at the IFN-gamma-activated sequence site, but Stat3 and Stat4 did
      not. Binding of Stat1 and Stat5 to the TRR were modified by progesterone in
      distinct ways. Estrogen suppressed the binding of Stat1 and Stat5 to the TRR.
      Mutation of gamma-activated sequence element reduced T-bet promoter activity,
      binding of Stat proteins to the TRR and regulation of the promoter by cytokines
      and hormones. In EECs, cytokine exposure caused phosphorylation of Janus kinase 2
      and TRR-bound Stat proteins; female steroid hormones altered only phosphorylation
      of TRR-bound Stat5. Although there is no autocrine IFN-gamma feedback loop in
      reproductive tract epithelial cells, an IL-15/T-bet positive feedback loop may
      exist. The implications of hormonally regulated T-bet expression are discussed.

PMID- 15860547
TI  - The delta e13 isoform of the calcitonin receptor forms a six-transmembrane domain
      receptor with dominant-negative effects on receptor surface expression and
      signaling.
AB  - The CTRdelta e13 splice variant of the rabbit calcitonin receptor, which lacks
      the 14 amino acids of the seventh transmembrane domain (TMD) that are encoded by
      exon 13, is poorly expressed on the cell surface, fails to mobilize intracellular
      calcium or activate Erk, and inhibits the cell surface expression of the full
      length C1a isoform. Nuclear magnetic resonance- and fluorescence-activated cell
      sorter-based experiments showed that the residual seventh TMD of CTRdelta e13
      fails to partition into the lipid bilayer, resulting in an extracellular C
      terminus. Truncating the receptor after residue 397 to delete the cytoplasmic
      tail resulted in reduced cell surface expression and an inability to mobilize
      intracellular calcium or activate Erk, but the truncated receptor did not inhibit
      C1a cell surface expression. In contrast, when the receptor was truncated after
      residue 374 to eliminate the entire seventh TMD domain and the C-terminal domain,
      the resulting receptor reduced the cell surface expression of C1a in a manner
      similar to that of CTRdelta e13. Thus, normal cell surface expression,
      mobilization of intracellular calcium, and Erk activation requires the
      cytoplasmic C-terminal tail of the CTR, whereas the absence of the seventh TMD in
      the transmembrane helical bundle causes the dominant-negative effect on the
      surface expression of C1a.

PMID- 15860548
TI  - Gene regulatory potential of nonsteroidal vitamin D receptor ligands.
AB  - The seco-steroid 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] is a promising
      drug candidate due to its pleiotropic function including the regulation of
      calcium homeostasis, bone mineralization and cellular proliferation,
      differentiation, and apoptosis. We report here a novel class of nonsteroidal
      compounds, represented by the bis-aromatic molecules CD4409, CD4420, and CD4528,
      as ligands of the 1alpha,25(OH)2D3 receptor (VDR). Taking the known
      diphenylmethane derivative LG190178 as a reference, this study provides molecular
      evaluation of the interaction of nonsteroidal ligands with the VDR. All four
      nonsteroidal compounds were shown to induce VDR-retinoid X receptor heterodimer
      complex formation on a 1alpha,25(OH)2D3 response element, stabilize the agonistic
      conformation of the VDR ligand-binding domain, enable the interaction of VDR with
      coactivator proteins and contact with their three hydroxyl groups the same
      residues within the ligand-binding pocket of the VDR as 1alpha,25(OH)2D3.
      Molecular dynamics simulations demonstrated that all four nonsteroidal ligands
      take a shape within the ligand-binding pocket of the VDR that is very similar to
      that of the natural ligand. CD4528 is mimicking the natural hormone best and was
      found to be in vitro at least five times more potent than LG190178. In living
      cells, CD4528 was only two times less potent than 1alpha,25(OH)2D3 and induced
      mRNA expression of the VDR target gene CYP24 in a comparable fashion. At a
      noncalcemic dose of 150 microg/kg, CD4528 showed in vivo a clear induction of
      CYP24 expression and therefore may be used as a lead compound for the development
      of therapeutics against psoriasis, osteoporosis, and cancer.

PMID- 15860549
TI  - Mutant prevention concentrations of ciprofloxacin for urinary tract infection
      isolates of Escherichia coli.
AB  - OBJECTIVES: To measure the mutant prevention concentration (MPC) of ciprofloxacin
      for a set of urinary tract infection (UTI) Escherichia coli isolates with
      different levels of susceptibility and determine whether MPC can be predicted
      from MIC. METHODS: MPC was defined as the lowest ciprofloxacin concentration that
      prevented the growth of resistant colonies when 10(10) bacteria were spread on
      solid medium and incubated for 96 h at 37 degrees C. MIC was measured by Etest.
      Bacteria surviving (persisting) at MPC were isolated and quantified from agar
      plugs taken after 96 h. The genes hipA and hipB were amplified by PCR from
      persisters and sequenced. RESULTS: Isolates with MICs above the NCCLS breakpoint
      for ciprofloxacin resistance (4 mg/L) typically have MPCs greater than 32 mg/L.
      Isolates with MICs below the breakpoint for ciprofloxacin susceptibility (1 mg/L)
      have MPCs up to 5 mg/L. MPC/MIC is approximately 16 for most susceptible isolates
      but there are several notable exceptions (MPC/MIC > 100). Resistant colonies
      arising one dilution step below MPC often had MIC > MPC. In every case tested, a
      proportion of cells survived (persisted), but did not grow into colonies, at MPC,
      without any increase in MIC. CONCLUSIONS: MPCs were determined for all
      ciprofloxacin-susceptible isolates. MPC is not accurately predicted from MIC.
      Colonies selected below MPC frequently have MIC > MPC, suggesting multiple
      mutations. A small fraction of cells from all strains tested survived for 96 h at
      MPC, without any associated increase in MIC. These survivors/persisters are not
      hipAB mutants.

PMID- 15860550
TI  - Triclosan inhibition of fatty acid synthesis and its effect on growth of
      Escherichia coli and Pseudomonas aeruginosa.
AB  - OBJECTIVES: To assess the effect of triclosan on fatty acid synthesis and to
      relate the inhibition of enoyl reductase to bacterial viability. METHODS: The
      effect of triclosan on fatty acid synthesis in a triclosan-resistant Escherichia
      coli and its sensitive counterpart and in Pseudomonas aeruginosa was investigated
      by measuring acetate incorporation into total lipid followed by analysis of fatty
      acid methyl esters by gas chromatography. Concurrently, the bactericidal effect
      of triclosan against these bacterial strains was assessed. RESULTS: Triclosan
      inhibited fatty acid biosynthesis in all the strains tested. However, for
      triclosan-resistant E. coli (MIC > 1000 mg/L) the concentration required to
      achieve inhibition was higher than that required for the susceptible counterpart.
      These concentrations did not significantly affect cell survival in any of the
      strains tested. CONCLUSIONS: This study shows that the inhibition of fatty acid
      biosynthesis by the bisphenol might be involved in its growth-inhibitory action
      and that other mechanisms are involved in its lethal effect. In addition,
      although microorganisms with a high triclosan MIC were still susceptible to the
      inhibitory effect of the bisphenol on fatty acid biosynthesis, a higher
      concentration of the compound was required. This suggested that triclosan
      bioavailability was different in these strains.

PMID- 15860551
TI  - Effects of piperacillin/tazobactam on Clostridium difficile growth and toxin
      production in a human gut model.
AB  - OBJECTIVES: Clostridium difficile infection (CDI) is a major cause of morbidity
      in the nosocomial environment. Antimicrobial agents such as the third-generation
      cephalosporins, lincosamides and aminopenicillins are well known for their
      propensity to induce CDI, but the definitive reasons why remain to be elucidated.
      Despite their broad spectrum of activity against both aerobic and anaerobic
      bacteria, the ureidopenicillins remain a class of antimicrobials infrequently
      associated with the development of CDI. METHODS: We used a triple-stage chemostat
      model that simulates the human gut to study the effects of the
      ureidopenicillin/beta-lactamase inhibitor combination piperacillin/tazobactam on
      gut bacterial populations and C. difficile. RESULTS: Piperacillin/tazobactam
      rapidly reduced all enumerated gut bacterial populations (including bacteroides,
      bifidobacteria and lactobacilli) below the limits of detection by the end of the
      piperacillin/tazobactam instillation period. Despite such widespread disruption
      of gut bacterial populations, C. difficile populations remained principally as
      spores, with no sustained proliferation or high-level cytotoxin production
      observed. CONCLUSIONS: Factors other than reduced colonization resistance must be
      responsible for determining whether CDI develops following antimicrobial
      administration. We believe the gut model is a promising approach for the study of
      C. difficile pathogenesis reflecting in vivo events likely to occur in CDI.

PMID- 15860552
TI  - Activity of three {beta}-lactams (ertapenem, meropenem and ampicillin) against
      intraphagocytic Listeria monocytogenes and Staphylococcus aureus.
AB  - OBJECTIVES: Assessment of the activity of three beta-lactams [ertapenem (a
      carbapenem with a prolonged half-life), meropenem and ampicillin] against
      intraphagocytic Listeria monocytogenes and Staphylococcus aureus. METHODS:
      Quantitative measurements of cfu changes in broth and in THP-1 macrophages (post
      phagocytosis) over time (5 and 24 h) at concentrations spanning from sub-MICs to
      C(max) (maximal concentration typically observed in patients' serum upon
      administration of conventional doses); morphological studies using an electron
      microscope; evaluation of drug stability (HPLC), protein binding (equilibrium
      dialysis) and measurement of drug cellular accumulation (microbiological assay).
      RESULTS: Ertapenem was unable to control L. monocytogenes growth in THP-1
      macrophages at all concentrations and times tested, even under conditions where
      ampicillin and meropenem were bactericidal. This behaviour could not be ascribed
      to drug instability, protein binding or lack of cell accumulation in comparison
      with ampicillin or meropenem. Ertapenem, ampicillin and meropenem were equally
      effective at reducing the post-phagocytosis inoculum of S. aureus ( approximately
      1 log cfu), and caused conspicuous changes in the morphology of intracellular
      bacteria consistent with their lysis. These effects were obtained, however, only
      at large multiples (100-fold or more) of the MIC maintained over 24 h. Because of
      the high intrinsic antimicrobial potency of the beta-lactams studied, these
      concentrations were below the C(max). CONCLUSIONS: Ertapenem will probably be
      ineffective against intraphagocytic forms of L. monocytogenes for reasons that
      remain to be discovered. Conversely, ertapenem could be an alternative to
      ampicillin and meropenem against intraphagocytic S. aureus since its longer half
      life may allow high concentrations to be maintained for more prolonged times.

PMID- 15860553
TI  - Raloxifene, a selective estrogen receptor modulator, reduces carrageenan-induced
      acute inflammation in normal and ovariectomized rats.
AB  - Raloxifene (RAL) is a selective estrogen receptor modulator presenting tissue
      specific agonist activity. The aim of this study was to examine whether RAL has
      an estrogenic effect on carrageenan-induced acute inflammation. Adult female rats
      were ovariectomized (OVX) 7 wk before edema or pleurisy to deplete circulating
      estrogens. Edema formation and selected inflammatory markers in inflamed paw
      tissue were measured in intact (sham-operated) and OVX rats. Groups of OVX rats
      were treated with RAL (1, 3, or 10 mg/kg) or 17beta-estradiol (E2, 25 microg/kg),
      and these treatments began 2 d after surgery and continued until carrageenan paw
      edema or pleurisy. Ovariectomy amplifies the inflammation, and we found that RAL,
      as well as E2, attenuates inflammation and tissue damage associated with paw
      edema and pleurisy. In treated rats, there is a decrease in edema development and
      formation, and in polymorphonuclear cell infiltration and migration, as shown by
      myeloperoxidase measurement and cell counting. RAL and E2 treatments decrease
      cyclooxygenase-2 and inducible nitric oxide synthase expression in inflamed areas
      and counteract the inhibition of peroxisome proliferators-activated receptor
      gamma expression caused by ovariectomy, restoring this receptor protein
      expression to sham-operated levels and identifying a possible peroxisome
      proliferators-activated receptor-dependent antiinflammatory effect of these
      drugs. Moreover, RAL and E2 increase cytoprotective heat shock protein 72
      expression, which seems to be closely associated with the remission of the
      inflammatory reaction. In addition, we confirm the antiinflammatory effect of RAL
      in male rats, using a single administration of RAL or E2.

PMID- 15860554
TI  - Interleukin (IL)-12-driven primary hypothyroidism: the contrasting roles of two
      Th1 cytokines (IL-12 and interferon-gamma).
AB  - IL-12, a prototypic T helper 1 cytokine, has been implicated in the pathogenesis
      of organ-specific autoimmune diseases, such as Hashimoto's thyroiditis, but
      reported to give conflicting results in murine models of lymphocytic thyroiditis.
      To determine the effects of chronic, local production of IL-12 within the thyroid
      gland, we created transgenic mice that express IL-12 p70 under the
      transcriptional control of the thyroglobulin promoter. Transgenics developed
      growth retardation, moderate primary hypothyroidism, and mild lymphocytic
      infiltration of the thyroid gland. The hypothyroidism was associated with
      increased mRNA levels of the sodium-iodide symporter, an increase partly due to a
      direct effect of IL-12 on the thyrocyte. Upon immunization with a suboptimal dose
      of mouse thyroglobulin, IL-12 transgenic mice developed a lymphocytic thyroiditis
      that was more frequent and severe than that observed in wild-type littermates.
      The disease-promoting effect of IL-12 was independent of interferon-gamma, as
      shown by the similar interferon-gamma levels in transgenics and controls. These
      findings highlight the contrasting roles of two T helper 1 cytokines and report a
      novel role of IL-12 on thyroid hormonogenesis.

PMID- 15860555
TI  - Dehydroepiandrosterone sulfate and allopregnanolone directly stimulate
      catecholamine production via induction of tyrosine hydroxylase and secretion by
      affecting actin polymerization.
AB  - Adrenal cortical cells of zona reticularis produce the neuroactive steroids
      dehydroepiandrosterone (DHEA), its sulfate ester dehydroepiandrosterone sulfate
      (DHEAS), and allopregnanolone (ALLO). An interaction between zona reticularis and
      adrenal medulla has been postulated based on their close proximity and their
      interwoven borders. The aim of this paper was to examine in vitro the possible
      paracrine effects of these steroids on catecholamine production from
      adrenomedullary chromaffin cells, using an established in vitro model of
      chromaffin cells, the PC12 rat pheochromocytoma cell line. We have found the
      following: 1) DHEA, DHEAS, and ALLO increased acutely (peak effect between 10-30
      min) and dose-dependently (EC50 in the nanomolar range) catecholamine levels
      (norepinephrine and dopamine). 2) It appears that the acute effect of these
      steroids involved actin depolymerization/actin filament disassembly, a fast
      response cellular system regulating trafficking of catecholamine vesicles.
      Specifically, 10(-6) m phallacidin, an actin filament stabilizer, completely
      prevented steroid-induced catecholamine secretion. 3) DHEAS and ALLO, but not
      DHEA, also affected catecholamine synthesis. Indeed, DHEAS and ALLO increased
      catecholamine levels at 24 h, an effect blocked by L-2-methyl-3-(-4
      hydroxyphenyl)alanine and 3-(hydrazinomethyl)phenol hydrochloride, inhibitors of
      tyrosine hydroxylase and L-aromatic amino acid decarboxylase, respectively,
      suggesting that this effect involved catecholamine synthesis. The latter
      hypothesis was confirmed by finding that DHEAS and ALLO increased both the mRNA
      and protein levels of tyrosine hydroxylase. In conclusion, our findings suggest
      that neuroactive steroids exert a direct tonic effect on adrenal catecholamine
      synthesis and secretion. These data associate the adrenomedullary malfunction
      observed in old age and neuroactive steroids.

PMID- 15860556
TI  - Expression of the mature luteinizing hormone receptor in rodent urogenital and
      adrenal tissues is developmentally regulated at a posttranslational level.
AB  - The LH receptor (LHR) is a G protein-coupled receptor involved in the regulation
      of ovarian and testicular functions. In this study we demonstrate novel and
      unexpected patterns of receptor expression and regulation in fetal and adult
      rodent urogenital and adrenal tissues. Two rat LHR promoter fragments
      (approximately 2 and 4 kb) were shown to direct expression of the lacZ reporter
      in transgenic mice to gonads, adrenal glands, and kidneys, starting at 14.5 d
      post coitum, and to genital tubercles, starting at 11.5 d post coitum. These
      tissues were also found to express the full-length LHR mRNA and protein during
      rat fetal development, but, importantly, only immature receptors carrying
      unprocessed N-linked glycans were detected. After birth, the receptor gene
      activity ceased, except in the gonads, which started to express the mature
      receptor carrying fully processed N-linked glycans. Surprisingly, both LHR mRNA
      and mature protein levels were up-regulated substantially in pregnant female
      adrenal glands and kidneys at a time that coincides with differentiation of fetal
      urogenital tissues. Taken together, these results indicate that the LHR protein
      is expressed constitutively in gonadal and nongonadal urogenital tissues as well
      in adrenal glands, but its final functional maturation at the posttranslational
      level appears to be developmentally and physiologically regulated.

PMID- 15860557
TI  - Mathematical model of paracrine interactions between osteoclasts and osteoblasts
      predicts anabolic action of parathyroid hormone on bone.
AB  - To restore falling plasma calcium levels, PTH promotes calcium liberation from
      bone. PTH targets bone-forming cells, osteoblasts, to increase expression of the
      cytokine receptor activator of nuclear factor kappaB ligand (RANKL), which then
      stimulates osteoclastic bone resorption. Intriguingly, whereas continuous
      administration of PTH decreases bone mass, intermittent PTH has an anabolic
      effect on bone, which was proposed to arise from direct effects of PTH on
      osteoblastic bone formation. However, antiresorptive therapies impair the ability
      of PTH to increase bone mass, indicating a complex role for osteoclasts in the
      process. We developed a mathematical model that describes the actions of PTH at a
      single site of bone remodeling, where osteoclasts and osteoblasts are regulated
      by local autocrine and paracrine factors. It was assumed that PTH acts only to
      increase the production of RANKL by osteoblasts. As a result, PTH stimulated
      osteoclasts upon application, followed by compensatory osteoblast activation due
      to the coupling of osteoblasts to osteoclasts through local paracrine factors.
      Continuous PTH administration resulted in net bone loss, because bone resorption
      preceded bone formation at all times. In contrast, over a wide range of model
      parameters, short application of PTH resulted in a net increase in bone mass,
      because osteoclasts were rapidly removed upon PTH withdrawal, enabling
      osteoblasts to rebuild the bone. In excellent agreement with experimental
      findings, increase in the rate of osteoclast death abolished the anabolic effect
      of PTH on bone. This study presents an original concept for the regulation of
      bone remodeling by PTH, currently the only approved anabolic treatment for
      osteoporosis.

PMID- 15860558
TI  - Oxytocin mediates the estrogen-dependent contractile activity of endothelin-1 in
      human and rabbit epididymis.
AB  - Epididymis is a sex steroid (androgen + estrogen)-sensitive duct provided with
      spontaneous motility, allowing sperm transport. We previously reported that the
      oxytocin (OT) receptor (OTR) mediates an estrogen-dependent increase in
      epididymal contractility. Because endothelin (ET)-1 also regulates epididymal
      motility, we tested its sex steroid dependence in a rabbit model. We demonstrated
      that estrogens up-regulate responsiveness to ET-1, which is reduced by blocking
      aromatase activity (letrozole, 2.5 mg/kg) or by triptorelin (2.9 mg/kg)-induced
      hypogonadism, whereas it is fully restored by estradiol valerate (3.3 mg/kg
      weekly) but not by testosterone enanthate (30 mg/kg weekly). However, changing
      sex steroid milieu did not affect either ET-1, its receptor gene, or protein
      expression. Two structurally distinct OTR-antagonists [(d(CH2)5(1), Tyr(Me)(2),
      Orn(8))-OT and atosiban] almost completely abolished ET-1 contractility, without
      competing for [125I]ET-1 binding, suggesting that OT/OTR partially mediates ET-1
      action. Immunohistochemical studies in human and rabbit epididymis demonstrated
      that both OT and its synthesis-associated protein, neurophysin I, are expressed
      in the epithelial cells facing the muscular layer, suggesting local OT
      production. Quantitative RT-PCR demonstrated a high abundance of OT transcripts
      in human epididymis. OT transcript was also originally detected and partially
      sequenced in rabbit epididymis. To verify whether ET-1 regulates OT release, we
      used rabbit epididymal epithelial cell cultures. These cells expressed a high
      density of [125I]ET-1 binding sites and responded to ET-1 with a dose-dependent
      OT release. Hence, we propose that an ET-1-induced OT/OTR system activation
      underlies the estrogen-dependent hyperresponsiveness to ET-1. These local sources
      might promote the spontaneous motility necessary for sperm transport.

PMID- 15860559
TI  - ABNER: an open source tool for automatically tagging genes, proteins and other
      entity names in text.
AB  - ABNER (A Biomedical Named Entity Recognizer) is an open source software tool for
      molecular biology text mining. At its core is a machine learning system using
      conditional random fields with a variety of orthographic and contextual features.
      The latest version is 1.5, which has an intuitive graphical interface and
      includes two modules for tagging entities (e.g. protein and cell line) trained on
      standard corpora, for which performance is roughly state of the art. It also
      includes a Java application programming interface allowing users to incorporate
      ABNER into their own systems and train models on new corpora.

PMID- 15860560
TI  - MatInspector and beyond: promoter analysis based on transcription factor binding
      sites.
AB  - MOTIVATION: Promoter analysis is an essential step on the way to identify
      regulatory networks. A prerequisite for successful promoter analysis is the
      prediction of potential transcription factor binding sites (TFBS) with reasonable
      accuracy. The next steps in promoter analysis can be tackled only with reliable
      predictions, e.g. finding phylogenetically conserved patterns or identifying
      higher order combinations of sites in promoters of co-regulated genes. RESULTS:
      We present a new version of the program MatInspector that identifies TFBS in
      nucleotide sequences using a large library of weight matrices. By introducing a
      matrix family concept, optimized thresholds, and comparative analysis, the
      enhanced program produces concise results avoiding redundant and false-positive
      matches. We describe a number of programs based on MatInspector allowing in-depth
      promoter analysis (DiAlignTF, FrameWorker) and targeted design of regulatory
      sequences (SequenceShaper).

PMID- 15860561
TI  - FSSA: a novel method for identifying functional signatures from structural
      alignments.
AB  - MOTIVATION: It is commonly believed that sequence determines structure, which in
      turn determines function. However, the presence of many proteins with the same
      structural fold but different functions suggests that global structure and
      function do not always correlate well. RESULTS: We propose a method for accurate
      functional annotation, based on identification of functional signatures from
      structural alignments (FSSA) using the Structural Classification of Proteins
      (SCOP) database. The FSSA method is superior at function discrimination and
      classification compared with several methods that directly inherit functional
      annotation information from homology inference, such as Smith-Waterman, PSI
      BLAST, hidden Markov models and structure comparison methods, for a large number
      of structural fold families. Our results indicate that the contributions of amino
      acid residue types and positions to structure and function are largely separable
      for proteins in multi-functional fold families.

PMID- 15860563
TI  - SWIFT (sequence-wide investigation with Fourier transform): a software tool for
      identifying proteins of a given class from the unannotated genome sequence.
AB  - BACKGROUND: The ever increasing number of sequenced genomes calls for new
      analysis techniques, which can benefit from the methodologies developed in the
      field of signal processing. METHODS: The present paper addresses the question of
      searching a pattern of amino acids (not necessarily completely specified) by
      means of the cross-correlation of complex sequences, obtained after suitable
      coding of the original amino acid sequence. Subsequently, the proposed algorithm
      provides a flexible strategy in setting the border between the accepted and
      rejected ORFs, by means of the k-means clustering of the candidate ORFs. The
      search for the class of proteins specified by the pattern is carried out from the
      most basic level, i.e. the DNA sequence, without sifting through an ensemble of
      previously determined ORFs. Thus, an exhaustive examination of all the
      occurrences of the pattern in the genome is performed. RESULTS: The application
      of the method to the search of surface proteins in Gram-positive bacteria
      witnesses its efficacy, in terms of both sensitivity and specificity. The
      comparison with the usual (and somewhat arbitrary) choice of setting a fixed
      value for the threshold length of the putative ORF confirms the validity of the
      proposed approach.

PMID- 15860562
TI  - iGNM: a database of protein functional motions based on Gaussian Network Model.
AB  - MOTIVATION: The knowledge of protein structure is not sufficient for
      understanding and controlling its function. Function is a dynamic property.
      Although protein structural information has been rapidly accumulating in
      databases, little effort has been invested to date toward systematically
      characterizing protein dynamics. The recent success of analytical methods based
      on elastic network models, and in particular the Gaussian Network Model (GNM),
      permits us to perform a high-throughput analysis of the collective dynamics of
      proteins. RESULTS: We computed the GNM dynamics for 20 058 structures from the
      Protein Data Bank, and generated information on the equilibrium dynamics at the
      level of individual residues. The results are stored on a web-based system called
      iGNM and configured so as to permit the users to visualize or download the
      results through a standard web browser using a simple search engine. Static and
      animated images for describing the conformational mobility of proteins over a
      broad range of normal modes are accessible, along with an online calculation
      engine available for newly deposited structures. A case study of the dynamics of
      20 non-homologous hydrolases is presented to illustrate the utility of the iGNM
      database for identifying key residues that control the cooperative motions and
      revealing the connection between collective dynamics and catalytic activity.

PMID- 15860564
TI  - A variational Bayesian mixture modelling framework for cluster analysis of gene
      expression data.
AB  - MOTIVATION: Accurate subcategorization of tumour types through gene-expression
      profiling requires analytical techniques that estimate the number of categories
      or clusters rigorously and reliably. Parametric mixture modelling provides a
      natural setting to address this problem. RESULTS: We compare a criterion for
      model selection that is derived from a variational Bayesian framework with a
      popular alternative based on the Bayesian information criterion. Using simulated
      data, we show that the variational Bayesian method is more accurate in finding
      the true number of clusters in situations that are relevant to current and future
      microarray studies. We also compare the two criteria using freely available
      tumour microarray datasets and show that the variational Bayesian method is more
      sensitive to capturing biologically relevant structure.

PMID- 15860565
TI  - Clinical applications of plasma circulating mRNA analysis in cases of gestational
      trophoblastic disease.

PMID- 15860566
TI  - Time-motion analysis of 6 cystic fibrosis mutation detection systems.
AB  - BACKGROUND: A dramatic increase in requests for routine cystic fibrosis (CF)
      carrier screening prompted us to conduct a time-motion analysis comparing
      commercially available CF testing platforms. Questions addressed in the study
      included: (a) How much time is required to perform each step involved in carrying
      out the assay procedure? (b) Which system requires the minimum number of manual
      manipulations to complete a typical run? (c) What workflow benefits can be
      achieved by automation? METHODS: We used a 96-sample run for comparisons and
      analyzed each of the 6 methods to determine the number of pipetting steps and
      manual manipulations, the labor and instrument time, and the total time required
      to perform the assay. The survey participants included a staff of 4 technologists
      who perform complex molecular assays regularly. Time required for each procedure
      was determined by direct observation and from work logs completed by the
      technologists. RESULTS: The total number of pipetting motions varied from 78 to
      344. Labor time ranged from 2.6 to 8.4 h, and total assay time from 7.6 to 13.7
      h. CONCLUSION: Time-motion analysis allowed identification of a method that
      minimized pipetting motions and thus reduced the risk of repetitive stress
      injury.

PMID- 15860567
TI  - Improved HPLC assay for measuring serum vitamin C with 1-methyluric acid used as
      an electrochemically active internal standard.

PMID- 15860568
TI  - Genotyping the hemophilia inversion hotspot by use of inverse PCR.
AB  - BACKGROUND: Factor VIII intron 22 inversions (Inv22) cause 40%-45% of severe
      cases of hemophilia A in all human populations. Currently, Inv22 can be analyzed
      either by Southern blotting or by rapid long-distance-PCR-based approaches. We
      describe an alternative method using inverse-PCR (I-PCR). METHODS: I-PCR involved
      3 steps: (a) BclI restriction; (b) self-ligation of restriction fragments,
      providing BclI rings; and (c) standard multiplex-PCR analysis. PCR was achieved
      by use of a set of 3 primers that yielded a 487-bp amplicon for the nonrearranged
      intragenic allele and a 559-bp amplicon for the Inv22 allele. Specific primer
      sites were targeted by masking relevant regions for human repeats and low
      complexity DNA. Inv22 I-PCR was applied to samples from 16 individuals (8 women
      and 8 men) representing 24 X chromosomes previously genotyped by Southern
      blotting. Additionally, we evaluated the sensitivity and the ability to assess
      eventual Inv22 carrier mosaicisms by experiments using artificial DNA mixtures
      (Inv22 + no-Inv22 male samples). RESULTS: Results for previously genotyped
      samples agreed with results of Southern blot analyses. As expected, cell
      composition of the artificial mosaic was linearly reflected by the relative
      intensities of Inv22 signals. I-PCR was estimated to detect Inv22-positive cells
      at concentrations as low as approximately 5%. CONCLUSION: The proposed technique
      provides a rapid tool for Inv22 genotyping.

PMID- 15860569
TI  - Diffusion of cytotoxic concentrations of nitric oxide generated luminally at the
      gastro-oesophageal junction of rats.
AB  - BACKGROUND: In humans, high concentrations of nitric oxide are generated
      luminally at the gastro-oesophageal junction through enterosalivary recirculation
      of dietary nitrate. AIM: To investigate whether luminal nitric oxide can diffuse
      into the adjacent digestive tissue and alter tissue integrity. METHODS: We
      designed an animal model using Wistar rats in which physiological concentrations
      of nitrite and acidified ascorbic acid were administered separately so that the
      two reactants first meet to form nitric oxide at the gastro-oesophageal junction.
      Luminal and tissue concentrations of nitric oxide were measured with an electrode
      and an electron paramagnetic resonance spectrometer, respectively. Concentrations
      of glutathione in the tissue were measured as a marker of nitrosative stress.
      RESULTS: High concentrations of luminal nitric oxide were generated locally at
      the gastro-oesophageal junction of nitrite administered rats, reproducing a
      phenomenon observed in humans. High levels of nitric oxide were also detected
      largely in the superficial epithelium of the gastro-oesophageal junction. The
      concentration of tissue glutathione at the gastro-oesophageal junction was
      significantly lower in nitrite administered rats compared with control rats,
      whereas that in the distal stomach was similar in the two rat groups.
      CONCLUSIONS: Using an animal model, this study demonstrated that nitric oxide
      generated in the lumen diffuses into the adjacent gastric tissue to a substantial
      degree, leading to localised consumption of glutathione in the tissue.
      Nitrosative stress induced by this mechanism may be involved in the high
      prevalence of inflammation and metaplasia, and subsequent development of
      neoplastic disease at this site.

PMID- 15860570
TI  - Quantitative in vivo microdialysis study on the influence of multidrug
      transporters on the blood-brain barrier passage of oxcarbazepine: concomitant use
      of hippocampal monoamines as pharmacodynamic markers for the anticonvulsant
      activity.
AB  - Various antiepileptic drugs were shown to be substrates for multidrug
      transporters at the level of the blood-brain barrier. These ATP-dependent efflux
      pumps actively limit brain accumulation of xenobiotics and drugs.
      Intrahippocampal oxcarbazepine perfusion in rat was previously shown to exert
      anticonvulsant effects associated with increases in extracellular dopamine and
      serotonin levels. In contrast, preliminary studies in our laboratory revealed
      that no anticonvulsant or monoaminergic effects could be obtained after systemic
      oxcarbazepine administration. The present in vivo microdialysis study was
      conducted to investigate the impact of the transport kinetics of oxcarbazepine
      across the blood-brain barrier on the observed treatment refractoriness. More
      precisely, the influence of intrahippocampal perfusion of verapamil, a P
      glycoprotein inhibitor, and probenecid, a multidrug resistance protein inhibitor,
      on the blood-brain barrier passage and anticonvulsant properties of oxcarbazepine
      were investigated in the focal pilocarpine model for limbic seizures.
      Simultaneously, the effects on hippocampal monoamines were studied as
      pharmacodynamic markers for the anticonvulsant activity. Although systemic
      oxcarbazepine administration alone failed in preventing the animals from
      developing seizures, coadministration with verapamil or probenecid offered
      complete protection. Concomitantly, significant increases in extracellular
      hippocampal dopamine and serotonin levels were observed within our previously
      defined anticonvulsant monoamine range. The present data indicate that
      oxcarbazepine is a substrate for multidrug transporters at the blood-brain
      barrier. Coadministration with multidrug transporter inhibitors significantly
      potentiates the anticonvulsant activity of oxcarbazepine and offers opportunities
      for treatment of pharmacoresistant epilepsy.

PMID- 15860571
TI  - A farnesoid x receptor-small heterodimer partner regulatory cascade modulates
      tissue metalloproteinase inhibitor-1 and matrix metalloprotease expression in
      hepatic stellate cells and promotes resolution of liver fibrosis.
AB  - The farnesoid X receptor (FXR) is expressed by and regulates hepatic stellate
      cells (HSCs). In the present study, we investigated whether 6-ethyl
      chenodeoxycholic acid (6-ECDCA or INT-747), a semisynthetic derivative of
      chenodeoxycholic acid (CDCA), modulates tissue metalloproteinase inhibitor (TIMP)
      1 and matrix metalloprotease (MMP)-2 expression/activity in HSCs and in the liver
      of rats rendered cirrhotic by 4-week administration of CCl(4). Exposure of HSCs
      to FXR ligands increases small heterodimer partner (SHP) mRNA by 3-fold and
      reduces basal and thrombin-stimulated expression of alpha1(I)collagen, alpha
      smooth muscle actin (alpha-SMA), TIMP-1, and TIMP-2 by approximately 60 to 70%,
      whereas it increased matrix metalloprotease (MMP)-2 activity by 2-fold. In
      coimmunoprecipitation, electromobility shift, and transactivation experiments,
      FXR activation/overexpression caused a SHP-dependent inhibition of JunD binding
      to its consensus element in the TIMP-1 promoter. Inhibition of TIMP-1 expression
      by SHP overexpression enhanced the sensitivity of HSCs to proapoptogenic stimuli.
      Administration of 3 mg/kg 6-ECDCA, but not 15 mg/kg ursodeoxycholic acid,
      resulted in early (3-5-day) induction of SHP and prevention of early up
      regulation of TIMP-1 mRNA induced by CCl(4). In the prevention protocol, 4-week
      administration of 6-ECDCA reduced alpha1(I)collagen, alpha-SMA, and TIMP-1 mRNA
      by 60 to 80%, whereas it increased MMP-2 activity by 5-fold. In the resolution
      protocol, administration of 3 mg/kg 6-ECDCA promoted liver fibrosis resolution
      and increased the apoptosis of nonparenchyma liver cells. By demonstrating that a
      FXR-SHP regulatory cascade promotes the development of a quiescent phenotype and
      increases apoptosis of HSCs, this study establishes that FXR ligands may be
      beneficial in treatment of liver fibrosis.

PMID- 15860572
TI  - Evaluation of PAI-039 [{1-benzyl-5-[4-(trifluoromethoxy)phenyl]-1H-indol-3
      yl}(oxo)acetic acid], a novel plasminogen activator inhibitor-1 inhibitor, in a
      canine model of coronary artery thrombosis.
AB  - We tested a novel, orally active inhibitor of plasminogen activator inhibitor-1
      (PAI-1) in a canine model of electrolytic injury. Dogs received by oral gavage
      either vehicle (control) or the PAI-1 inhibitor PAI-039 [{1-benzyl-5-[4
      (trifluoromethoxy)phenyl]-1H-indol-3-yl}(oxo)acetic acid] (1, 3, and 10 mg/kg)
      and were subjected to electrolytic injury of the coronary artery. PAI-039 caused
      prolongation in time to coronary occlusion (control, 31.7 +/- 6.3 min; 3 mg/kg
      PAI-039, 66.0 +/- 6.4 min; 10 mg/kg, 56.7 +/- 7.4 min; n = 5-6; p < 0.05) and a
      reduced thrombus weight (control, 7.6 +/- 1.5 mg; 10 mg/kg PAI-039, 3.6 +/- 1.0
      mg; p < 0.05). Although occlusive thrombosis was observed across all groups based
      upon the absence of measurable blood flow, a high incidence (>60%) of spontaneous
      reperfusion occurred only in those groups receiving PAI-039. Spontaneous
      reperfusion in the 10 mg/kg PAI-039 group accounted for total blood flow (area
      under the curve of coronary blood flow) of 99.6 +/- 11.7 ml after initial
      thrombotic occlusion (p < 0.05 compared with control). Plasma PAI-1 activity was
      reduced in all drug-treated groups (percentage of reduction in activity p < 0.05;
      10 mg/kg PAI-039), whereas ADP-, 9,11-dideoxy-11alpha,9alpha
      epoxymethanoprostaglandin F(2alpha) (U46619)-, and collagen-induced platelet
      aggregation, as well as template bleeding and prothrombin time, remained
      unaffected by PAI-039. Ex vivo clot lysis analysis revealed normal clot formation
      but accelerated clot lysis in PAI-039-treated groups. The pharmacokinetic profile
      of PAI-039 indicated an oral bioavailability of 43 +/- 15.3% and a plasma half
      life of 6.2 +/- 1.3 h. In conclusion, PAI-039 is an orally active prothrombolytic
      drug that inhibits PAI-1 and accelerates fibrinolysis while maintaining normal
      coagulation in a model of coronary occlusion.

PMID- 15860573
TI  - Mu opioid receptor coupling to Gi/o proteins increases during postnatal
      development in rat brain.
AB  - Mu opioid receptors are densely expressed within rat striatum and are
      concentrated in anatomically discrete patches called striosomes. The density of
      striosomal mu receptors remains relatively constant during postnatal development,
      but little is known about their functional maturation. We examined the extent of
      G protein coupling by mu opioid receptors in rat brain during development,
      focusing on striosomes within the striatum because of receptor density. The mu
      receptors were quantified using [(3)H][d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin
      (DAMGO) autoradiography. Adjacent sections were analyzed for DAMGO-stimulated
      guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding to assess
      mu receptor activation of G(i/o) proteins. Striosomal mu receptor expression
      increased only slightly between postnatal day 5 and adult. In contrast, mu
      receptor-stimulated [(35)S]GTPgammaS binding increased from 0.13 to 2.6 fmol/mg
      tissue over the same period, a 20-fold difference. The ratio of specific DAMGO
      stimulated [(35)S]GTPgammaS binding to [(3)H]DAMGO binding, representing the
      relative number of G proteins activated per receptor, increased 19-fold between
      postnatal day 5 and adult. Similar patterns were observed throughout the striatum
      and other brain regions such as the nucleus accumbens, although the extent of
      change varied from region to region. These data indicate that mu opioid receptors
      exhibit enhanced function in the adult rat brain compared with the neonate. These
      data also suggest that this increase in G protein coupling is developmentally
      regulated and that in the developing rat brain the density of mu opioid receptor
      expression may not necessarily correlate with receptor activation of G proteins.

PMID- 15860574
TI  - Hepatic cytochrome P450 gene regulation during endotoxin-induced inflammation in
      nuclear receptor knockout mice.
AB  - Inflammatory agents such as lipopolysaccharide (LPS) down-regulate the hepatic
      expression of many cytochrome P450 (P450) mRNAs and proteins. Previous studies
      suggested that suppression of some P450 mRNAs could involve the regulation or
      modulation of the nuclear receptors peroxisome proliferator-activated receptor
      alpha (PPARalpha) or pregnane X receptor (PXR). To determine the involvement of
      these receptors in P450 down-regulation, PPARalpha knockout (KO), PXR KO, and
      appropriate wild-type (WT) mice were administered either saline or 1 mg/kg LPS.
      Hepatic mRNA and protein expression of several P450 isoforms, interleukin (IL)
      1beta, IL-6, tumor necrosis factor (TNF) alpha, alpha1-acid glycoprotein (AGP),
      and fibrinogen (FBG) were examined 16 h later. LPS administration significantly
      decreased the hepatic expression of CYP1A2, 2A5, 2C29, 2E1, 3A11, 4A10, and 4A14
      mRNAs in both groups of PPARalpha and PXR mice, whereas CYP3A13 mRNA was
      increased slightly in PPARalpha WT and KO mice, but not in PXR mice. Effects of
      LPS administration on mouse hepatic P450 proteins (probed using rat P450 2C, 3A,
      4A, and 2E antibodies) were consistent with mRNA results in most cases. LPS
      treatment significantly increased IL-1beta, IL-6, TNFalpha, AGP, and FBG mRNA in
      both PPARalpha and PXR mice, with the greatest effect observed with TNFalpha.
      Because decreases in P450 mRNA expression were essentially identical in both WT
      and KO mice for both nuclear receptors, these data indicate that down-regulation
      of P450 during inflammation does not require the nuclear receptors PPARalpha and
      PXR.

PMID- 15860575
TI  - Human CD34-positive hematopoietic stem cells constitute targets for carcinogenic
      polycyclic aromatic hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are major carcinogenic environmental
      contaminants known to exert bone marrow toxicity and to induce leukemias,
      suggesting that these chemicals target hematopoietic stem cells. To investigate
      this hypothesis, we studied the effects of PAHs on cell proliferation and
      differentiation in human hematopoietic CD34+ cell cultures. Benzo(a)pyrene (BP),
      a prototypical PAH, was shown to markedly impair CD34+ cell expansion and to
      inhibit CD34+ cell differentiation into various hematological cell lineages,
      including erythroid, granulomacrophagic, and megakaryocytic lineages. This was
      associated with the induction of a caspase- and mitochondrion-related apoptosis
      process. CD34+ progenitor cells were found to exhibit functional expression of
      the aryl hydrocarbon receptor (AhR), and the use of the pure AhR antagonist 3'
      methoxy-4'-nitroflavone partially counteracted the deleterious effects of BP in
      CD34+ cell cultures, underlining the involvement of AhR in BP toxicity.
      Additional events such as CYP1A1/1B1-dependent PAH metabolism and adduct
      formation were also required since 1) 2,3,7,8-tetrachlorodibenzo-p-dioxin, a very
      potent ligand of the AhR that is poorly metabolized and therefore does not
      generate reactive metabolites in contrast to PAHs, failed to affect CD34+ cell
      expansion; 2) the CYP1A1/1B1 inhibitor alpha-naphthoflavone blocked both BP
      adduct formation and BP toxicity; and 3) benzo(a)pyrene-trans-7,8-dihydrodiol
      9,10-epoxide, a highly reactive BP metabolite, exerted a marked toxicity toward
      CD34+ cell cultures. Overall, these data indicate that human hematopoietic CD34+
      cells can bioactivate chemical carcinogens such as PAHs and, in this way,
      constitute targets for such carcinogenic environmental contaminants.

PMID- 15860576
TI  - Characterization in rats of the anxiolytic potential of ELB139 [1-(4
      chlorophenyl)-4-piperidin-1-yl-1,5-dihydro-imidazol-2-on], a new agonist at the
      benzodiazepine binding site of the GABAA receptor.
AB  - Benzodiazepines are among the most effective drugs for the treatment of anxiety
      disorders. However, their use is limited by undesired side effects, including
      sedation, development of tolerance, and drug abuse. The aim of this study was to
      evaluate the pharmacological profile of ELB139 [1-(4-chlorophenyl)-4-piperidin-1
      yl-1,5-dihydro-imidazol-2-on] in different models of anxiety and to correlate
      these effects with its activity in vitro. ELB139 binds with an IC(50) of 1390 nM
      to the flunitrazepam binding site in rat forebrain cortical membranes. In rat
      hippocampal neurons, ELB139 potentiated GABA-induced currents without reaching
      the maximum effect of diazepam, indicating a partial benzodiazepine agonism. The
      potentiation was antagonized by the benzodiazepine antagonist flumazenil. ELB139
      (10 and 30 mg/kg p.o.) was active in three different animal models of anxiety,
      i.e., in the elevated plus-maze, the light and dark box, and the Vogel conflict
      test. The anxiolytic activity in the elevated plus-maze was almost completely
      reversed by flumazenil (5 mg/kg i.p.), indicating that interaction with the
      benzodiazepine binding site is central to the pharmacological activity. No hint
      of sedation was observed at the doses tested in the three anxiety models and the
      open field. Also, no development of tolerance was observed within 6 weeks b.i.d.
      treatment with ELB139 in the elevated plus-maze test. In summary, ELB139 elicits
      strong effects on anxiety-related behavior in rats mediated by its benzodiazepine
      like activity without showing sedation or the development of tolerance, a major
      side effect of benzodiazepines. These characteristics make the compound a prime
      candidate for clinical development.

PMID- 15860577
TI  - Studies of the biogenic amine transporters. XI. Identification of a 1-[2-[bis(4
      fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR12909) analog that
      allosterically modulates the serotonin transporter.
AB  - Previous studies identified partial inhibitors of serotonin (5-HT) transporter
      and dopamine transporter binding. We report here on a partial inhibitor of 5-HT
      transporter (SERT) binding identified among a group of 1-[2-[bis(4
      fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine analogs (4-[2-[bis(4
      fluorophenyl)-methoxy]ethyl]-1-(2-trifluoromethyl-benzyl)-piperidine; TB-1-099).
      Membranes were prepared from rat brains or human embryonic kidney cells
      expressing the cloned human dopamine (hDAT), serotonin (hSERT), and
      norepinephrine (hNET) transporters. beta-(4'-(125)Iodophenyl)tropan-2beta
      carboxylic acid methyl ester ([(125)I]RTI-55) binding and other assays followed
      published procedures. Using rat brain membranes, TB-1-099 weakly inhibited DAT
      binding (K(i) = 439 nM), was inactive at NET binding ([(3)H]nisoxetine), and
      partially inhibited SERT binding with an extrapolated plateau ("A" value) of 20%.
      Similarly, TB-1-099 partially inhibited [(125)I]RTI-55 binding to hSERT with an
      extrapolated plateau (A value) of 14%. Upon examining the effect of increasing
      concentrations of TB-1-099 on the apparent K(d) and B(max) of [(125)I]RTI-55
      binding to hSERT, we found that TB-1-099 decreased the B(max) in a dose-dependent
      manner and affected the apparent K(d) in a manner well described by a sigmoid
      dose-response curve. TB-1-099 increased the K(d) but not to the magnitude
      expected for a competitive inhibitor. In rat brain synaptosomes, TB-1-099
      noncompetitively inhibited [(3)H]5-HT, but not [(3)H]dopamine, uptake.
      Dissociation experiments indicated that TB-1-099 promoted the rapid dissociation
      of a small component of [(125)I]RTI-55 binding to hSERT. Association experiments
      demonstrated that TB-1-099 slowed [(125)I]RTI-55 binding to hSERT in a manner
      unlike that of the competitive inhibitor indatraline. Viewed collectively, these
      results support the hypothesis that TB-1-099 allosterically modulates hSERT
      binding and function.

PMID- 15860578
TI  - Representations of faces and body parts in macaque temporal cortex: a functional
      MRI study.
AB  - Human neuroimaging studies suggest that areas in temporal cortex respond
      preferentially to certain biologically relevant stimulus categories such as faces
      and bodies. Single-cell studies in monkeys have reported cells in inferior
      temporal cortex that respond selectively to faces, hands, and bodies but provide
      little evidence of large clusters of category-specific cells that would form
      "areas." We probed the category selectivity of macaque temporal cortex for
      representations of monkey faces and monkey body parts relative to man-made
      objects using functional MRI in animals trained to fixate. Two face-selective
      areas were activated bilaterally in the posterior and anterior superior temporal
      sulcus exhibiting different degrees of category selectivity. The posterior face
      area was more extensively activated in the right hemisphere than in the left
      hemisphere. Immediately adjacent to the face areas, regions were activated
      bilaterally responding preferentially to body parts. Our findings suggest a
      category-selective organization for faces and body parts in macaque temporal
      cortex.

PMID- 15860579
TI  - bptA (bbe16) is essential for the persistence of the Lyme disease spirochete,
      Borrelia burgdorferi, in its natural tick vector.
AB  - Borrelia burgdorferi (Bb), the agent of Lyme disease, is a zoonotic spirochetal
      bacterium that depends on arthropod (Ixodes ticks) and mammalian (rodent) hosts
      for its persistence in nature. The quest to identify borrelial genes responsible
      for Bb's parasitic dependence on these two diverse hosts has been hampered by
      limitations in the ability to genetically manipulate virulent strains of Bb.
      Despite this constraint, we report herein the inactivation and genetic
      complementation of a linear plasmid-25-encoded gene (bbe16) to assess its role in
      the virulence, pathogenesis, and survival of Bb during its natural life cycle.
      bbe16 was found to potentiate the virulence of Bb in the murine model of Lyme
      borreliosis and was essential for the persistence of Bb in Ixodes scapularis
      ticks. As such, we have renamed bbe16 a gene encoding borrelial persistence in
      ticks (bpt)A. Although protease accessibility experiments suggested that BptA as
      a putative lipoprotein is surface-exposed on the outer membrane of Bb, the
      molecular mechanism(s) by which BptA promotes Bb persistence within its tick
      vector remains to be elucidated. BptA also was shown to be highly conserved (>88%
      similarity and >74% identity at the deduced amino acid levels) in all Bb sensu
      lato strains tested, suggesting that BptA may be widely used by Lyme borreliosis
      spirochetes for persistence in nature. Given Bb's absolute dependence on and
      intimate association with its arthropod and mammalian hosts, BptA should be
      considered a virulence factor critical for Bb's overall parasitic strategy.

PMID- 15860580
TI  - The Sca-1 cell surface marker enriches for a prostate-regenerating cell
      subpopulation that can initiate prostate tumorigenesis.
AB  - Sca-1 (stem cell antigen-1) enriches for murine prostate cells capable of
      regenerating tubular structures containing basal and luminal cell lineages in a
      dissociated cell prostate regeneration system. Sca-1(+) fractions are enriched
      for cells at the G(0) stage of the cell cycle, and Sca-1(+) cells cluster in the
      proximal region of prostatic tubules where replication-quiescent cells have been
      localized. Castration-induced enrichment for androgen-independent cells results
      in a concomitant enrichment for Sca-1(+) cells. Genetic perturbations of PTEN/AKT
      signaling in prostate-regenerating cells leads to the initiation of
      tumorigenesis, and cancer progression is associated with a dramatic increase in
      Sca-1(+) cells. Sca-1-enriched prostate-regenerating cells possess multiple
      stem/progenitor cell properties and can serve as targets for cancer initiation.

PMID- 15860581
TI  - A genetically defined mouse ovarian carcinoma model for the molecular
      characterization of pathway-targeted therapy and tumor resistance.
AB  - Cell lines and tumors with defined genetic alterations provide ideal systems in
      which to test the molecular mechanisms of tumor sensitivity to pathway-targeted
      therapy. We have generated mouse ovarian epithelial tumor cell lines that contain
      various combinations of genetic alterations in the p53, c-myc, K-ras and Akt
      genes. Using both in vitro and in vivo approaches, we investigated the effect of
      rapamycin on cell proliferation, tumor growth, and the accumulation of peritoneal
      ascites. We demonstrated that rapamycin effectively inhibits the growth of tumors
      that rely on Akt signaling for proliferation, whereas tumors in which Akt
      signaling is not the driving force in proliferation are resistant to rapamycin.
      The introduction of activated Akt to the rapamycin-resistant cells does not
      render the cells susceptible to rapamycin if they can use alternative pathways
      for survival and proliferation. Accordingly, the rapamycin-sensitive tumors
      develop resistance to rapamycin when presented with alternative survival
      pathways, such as the mitogen-activated extracellular kinase signaling pathway.
      The combination of rapamycin and the mitogen-activated extracellular kinase
      inhibitor PD98059 is required to diminish proliferation in these cell lines. Our
      results indicate that mammalian target of rapamycin inhibitors may be effective
      in a subset of tumors that depend on Akt activity for survival but not effective
      in all tumors that exhibit Akt activation. Tumors with alternative survival
      pathways may require the inactivation of multiple individual pathways for
      successful treatment.

PMID- 15860582
TI  - Neutrophil microtubules suppress polarity and enhance directional migration.
AB  - How do microtubules, which maintain and direct polarity of many eukaryotic cells,
      regulate polarity of blood neutrophils? In sharp contrast to most cells,
      disrupting a neutrophil's microtubule network with nocodazole causes it to
      polarize and migrate [Niggli, V. (2003) J. Cell Sci. 116, 813-822]. Nocodazole
      induces the same responses in differentiated HL-60 cells, a model neutrophil cell
      line, and reduces their chemotactic prowess by causing them to pursue abnormally
      circuitous paths in migrating toward a stationary point source of an attractant,
      f-Met-Leu-Phe (fMLP). The chemotactic defect stems from dramatic nocodazole
      induced imbalance between the divergent, opposed fMLP-induced "backness" and
      "frontness" signals responsible for neutrophil polarity. Nocodazole (i)
      stimulates backness by increasing Rho- and actomyosin-dependent contractility, as
      reported by Niggli, and also (ii) impairs fMLP-dependent frontness: pseudopods
      are flatter, contain less F-actin, and show decreased membrane translocation of
      PH-Akt-GFP, a fluorescent marker for 3'-phosphoinositide lipids. Inhibiting
      backness with a pharmacologic inhibitor of a Rho-dependent kinase substantially
      reverses nocodazole's effects on chemotaxis, straightness of migration paths,
      morphology, and PH-Akt-GFP translocation. Thus, microtubules normally balance
      backness vs. frontness signals, preventing backness from reducing the strength of
      pseudopods and from impairing directional migration.

PMID- 15860583
TI  - Immunomodulatory oligonucleotides containing a cytosine-phosphate-2'-deoxy-7
      deazaguanosine motif as potent toll-like receptor 9 agonists.
AB  - Bacterial DNA and synthetic oligomers containing CpG dinucleotides activate the
      immune system through Toll-like receptor (TLR) 9. Here, we compare the
      immunostimulatory activity of three immunomers with different nucleotide
      sequences containing a synthetic cytosine-phosphate-2'-deoxy-7-deazaguanosine
      dinucleotide (CpR), called immunomodulatory oligonucleotides (IMOs), in mouse,
      human, and monkey systems. IMOs induced IL-12 and IFN-gamma secretion more than a
      control non-CpG IMO in mice. All three IMOs activated HEK293 cells expressing
      TLR9 but not TLR3, -7, or -8. IMOs induced human B-cell proliferation and
      enhanced expression of CD86 and CD69 surface markers on B cells. The three IMOs
      induced CD86 expression on human plasmacytoid dendritic cells, but only IMOs that
      contained a 5'-terminal TCR nucleotide sequence induced IFN-alpha secretion. A
      sequence that forms a duplex structure also was required for IFN-alpha induction
      in human peripheral blood mononuclear cell cultures. IMOs induced chemokine and
      cytokine gene expression in human peripheral blood mononuclear cells. In monkeys,
      all three IMOs induced transient changes in peripheral blood leukocytes and
      lymphocytes and activated B and T lymphocytes. All three IMOs induced IFN-alpha
      in vivo in monkeys; the IMO sequence that forms a stable secondary structure
      induced the highest levels of IFN-alpha. These studies are, to our knowledge, the
      first comprehensive studies to compare the activity of IMOs containing synthetic
      stimulatory CpR dinucleotides in mouse, monkey, and human systems. These results
      suggest that IMOs induce strong and rapid immunostimulation and that the CpR
      dinucleotide is recognized by TLR9, leading to immune-cell activation and
      cytokine secretion in vitro and in vivo.

PMID- 15860584
TI  - Leptosphaeria rhodopsin: bacteriorhodopsin-like proton pump from a eukaryote.
AB  - Bacteriorhodopsin-like proteins provide archaea and eubacteria with a unique
      bioenergetic pathway comprising light-driven transmembrane proton translocation
      by a single retinal-binding protein. Recently, homologous proteins were found to
      perform photosensory functions in lower eukaryotes, but no active ion transport
      by eukaryotic rhodopsins was detected. By demonstrating light-driven proton
      pumping in a fungal rhodopsin from Leptosphaeria maculans, we present a case of a
      retinal-based proton transporter from a eukaryote. This result implies that in
      addition to oxidative phosphorylation and chlorophyll photosynthesis, some lower
      eukaryotes may have retained the archaeal route of building an electrochemical
      transmembrane gradient of protons.

PMID- 15860585
TI  - Static and dynamic quantum effects in molecular liquids: a linearized path
      integral description of water.
AB  - Structure, transport properties, and IR spectra including quantum effects are
      calculated for a flexible simple point charge model of liquid water. A recently
      introduced combination of a variational local harmonic description of the liquid
      potential surface and the classical Wigner approximation for the dynamics is
      used. The potential energy and interatomic radial distribution functions are in
      good agreement with accurate results from the literature and are significantly
      closer to experiment than predictions found from classical theory. The oxygen and
      hydrogen velocity correlation functions are also calculated, and the
      corresponding molecular diffusion coefficient is in good accord with existing
      theoretical estimates including quantum effects. Of most interest, an ab initio
      quantum correction factor is obtained to correct the far IR spectrum of water.
      When corrected, a spectrum based on a classical simulation yields results that
      agree well with experiment. Combined with internal tests of consistency, these
      observations indicate that this quite flexible approach will be effective for a
      variety of molecular problems involving the dynamics of light nuclei.

PMID- 15860586
TI  - Winter disruption of the circadian clock in chestnut.
AB  - Circadian clock performance during winter dormancy has been investigated in
      chestnut by using as marker genes CsTOC1 and CsLHY, which are homologous to
      essential components of the central circadian oscillator in Arabidopsis. During
      vegetative growth, mRNA levels of these two genes in chestnut seedlings and adult
      plants cycled daily, as expected. However, during winter dormancy, CsTOC1 and
      CsLHY mRNA levels were high and did not oscillate, indicating that the circadian
      clock was altered. A similar disruption was induced by chilling chestnut
      seedlings (to 4 degrees C). Normal cycling resumed when endodormant or cold
      treated plants were returned to 22 degrees C. The behavior of CsTOC1 and CsLHY
      during a cold response reveals a relevant aspect of clock regulation not yet
      encountered in Arabidopsis.

PMID- 15860587
TI  - Interfacial folding and membrane insertion of designed peptides studied by
      molecular dynamics simulations.
AB  - The mechanism of interfacial folding and membrane insertion of designed peptides
      is explored by using an implicit membrane generalized Born model and replica
      exchange molecular dynamics. Folding/insertion simulations initiated from fully
      extended peptide conformations in the aqueous phase, at least 28 A away from the
      membrane interface, demonstrate a general mechanism for structure formation and
      insertion (when it occurs). The predominately hydrophobic peptides from the
      synthetic WALP and TMX series first become localized at the membrane-solvent
      interface where they form significant helical secondary structure via a helix
      turn-helix motif that inserts the central hydrophobic residues into the membrane
      interior, and then fluctuations occur that provide a persistent helical structure
      throughout the peptide and it inserts with its N-terminal end moving across the
      membrane. More specifically, we observed that: (i) the WALP peptides (WALP16,
      WALP19, and WALP23) spontaneously insert in the membrane as just noted; (ii) TMX
      1 also inserts spontaneously after a similar mechanism and forms a transmembrane
      helix with a population of approximately 50% at 300 K; and (iii) TMX-3 does not
      insert, but exists in a fluctuating membrane interface-bound form. These findings
      are in excellent agreement with available experimental data and demonstrate the
      potential for new implicit solvent/membrane models together with advanced
      simulation protocols to guide experimental programs in exploring the nature and
      mechanism of membrane-associated folding and insertion of biologically important
      peptides.

PMID- 15860588
TI  - Spatiotemporal maturation patterns of murine brain quantified by diffusion tensor
      MRI and deformation-based morphometry.
AB  - Highly heterogeneous spatiotemporal patterns of maturation of the murine brain
      during the first 80 postnatal days were examined by high-dimensional deformation
      based morphometry applied to high-resolution diffusion tensor MRIs. The
      maturation profile revealed a sharp contrast between tissue anisotropy changes in
      the cortex and in major white-matter fibers. Radially oriented tissue anisotropy
      was measured during the first postnatal week in cortical regions, reflecting the
      underlying columnar organization of the cortex. Subsequently, tissue anisotropy
      reduced rapidly, potentially reflecting the growth of randomly oriented dendritic
      trees that reduce tissue coorientation. Distinct anisotropy patterns were also
      observed along layer I of the cortex and were attributed to thin fibers oriented
      parallel to the outer surface. Last, spatially complex patterns of maturation
      were measured in all major axonal pathways and in the hippocampus, caudate
      putamen, and cerebellum. This analysis provides a framework for quantifying
      normative maturation patterns against which phenotypes of mice of different
      genetic and environmental backgrounds can be contrasted.

PMID- 15860589
TI  - Ivory-billed woodpecker (Campephilus principalis) persists in continental North
      America.
AB  - The ivory-billed woodpecker (Campephilus principalis), long suspected to be
      extinct, has been rediscovered in the Big Woods region of eastern Arkansas.
      Visual encounters during 2004 and 2005, and analysis of a video clip from April
      2004, confirm the existence of at least one male. Acoustic signatures consistent
      with Campephilus display drums also have been heard from the region. Extensive
      efforts to find birds away from the primary encounter site remain unsuccessful,
      but potential habitat for a thinly distributed source population is vast (over
      220,000 hectares).

PMID- 15860591
TI  - Earth's energy imbalance: confirmation and implications.
AB  - Our climate model, driven mainly by increasing human-made greenhouse gases and
      aerosols, among other forcings, calculates that Earth is now absorbing 0.85 +/-
      0.15 watts per square meter more energy from the Sun than it is emitting to
      space. This imbalance is confirmed by precise measurements of increasing ocean
      heat content over the past 10 years. Implications include (i) the expectation of
      additional global warming of about 0.6 degrees C without further change of
      atmospheric composition; (ii) the confirmation of the climate system's lag in
      responding to forcings, implying the need for anticipatory actions to avoid any
      specified level of climate change; and (iii) the likelihood of acceleration of
      ice sheet disintegration and sea level rise.

PMID- 15860590
TI  - Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1
      antibodies.
AB  - The design of a human immunodeficiency virus-1 (HIV-1) immunogen that can induce
      broadly reactive neutralizing antibodies is a major goal of HIV-1 vaccine
      development. Although rare human monoclonal antibodies (mAbs) exist that broadly
      neutralize HIV-1, HIV-1 envelope immunogens do not induce these antibody
      specificities. Here we demonstrate that the two most broadly reactive HIV-1
      envelope gp41 human mAbs, 2F5 and 4E10, are polyspecific autoantibodies reactive
      with the phospholipid cardiolipin. Thus, current HIV-1 vaccines may not induce
      these types of antibodies because of autoantigen mimicry of the conserved
      membrane-proximal epitopes of the virus. These results may have important
      implications for generating effective neutralizing antibody responses by using
      HIV-1 vaccines.

PMID- 15860592
TI  - Kinetic evidence for five-coordination in AlOH(aq)2+ ion.
AB  - Trivalent aluminum ions are important in natural bodies of water, but the
      structure of their coordination shell is a complex unsolved problem. In strong
      acid (pH < 3.0), Al(III) exists almost entirely as the octahedral Al(H2O)6(3+)
      ion, whereas in basic conditions (pH > 7), a tetrahedral Al(OH)(4- structure
      prevails. In the biochemically and geochemically critical pH range of 4.3 to 7.0,
      the ion structures are less clear. Other hydrolytic species, such as AlOH(aq)2+,
      exist and are traditionally assumed to be hexacoordinate. We show, however, that
      the kinetics of proton and water exchange on aqueous Al(III), coupled with Car
      Parrinello simulations, support a five-coordinate Al(H2O)4OH2+ ion as the
      predominant form of AlOH(aq)2+ under ambient conditions. This result contrasts
      Al(III) with other trivalent metal aqua ions, for which there is no evidence for
      stable pentacoordinate hydrolysis products.

PMID- 15860594
TI  - Benefits of women in science.

PMID- 15860595
TI  - NASA. Life science research on space station is headed for big cuts.

PMID- 15860593
TI  - TLR11 activation of dendritic cells by a protozoan profilin-like protein.
AB  - Mammalian Toll-like receptors (TLRs) play an important role in the innate
      recognition of pathogens by dendritic cells (DCs). Although TLRs are clearly
      involved in the detection of bacteria and viruses, relatively little is known
      about their function in the innate response to eukaryotic microorganisms. Here we
      identify a profilin-like molecule from the protozoan parasite Toxoplasma gondii
      that generates a potent interleukin-12 (IL-12) response in murine DCs that is
      dependent on myeloid differentiation factor 88. T. gondii profilin activates DCs
      through TLR11 and is the first chemically defined ligand for this TLR. Moreover,
      TLR11 is required in vivo for parasite-induced IL-12 production and optimal
      resistance to infection, thereby establishing a role for the receptor in host
      recognition of protozoan pathogens.

PMID- 15860596
TI  - National academies. Panel would entrust stem cell research to local oversight.

PMID- 15860598
TI  - Earth sciences. Earth observation program 'at risk,' academy warns.

PMID- 15860597
TI  - Nuclear fusion. Tabletop accelerator breaks 'cold fusion' jinx but won't yield
      energy, physicists say.

PMID- 15860599
TI  - Department of energy. Falling budget could force choice between nuclear science
      facilities.

PMID- 15860600
TI  - Science policy. Marburger asks social scientists for a helping hand in
      interpreting data.

PMID- 15860601
TI  - U.S. public sector. Agency kills new performance rules.

PMID- 15860602
TI  - Public health. High hopes and dilemmas for a cervical cancer vaccine.

PMID- 15860603
TI  - Public health. HPV's peculiarities, from infection to disease.

PMID- 15860604
TI  - Information sharing. Europe steps into the open with plans for electronic
      archives.

PMID- 15860605
TI  - Developmental biology. Combing over the Polycomb group proteins.

PMID- 15860606
TI  - U.S. education. Kansas gears up for another battle over teaching evolution.

PMID- 15860607
TI  - A cry for help from Kansas.

PMID- 15860608
TI  - Ethics of tobacco company funding.

PMID- 15860609
TI  - Comment on "Ecosystem properties and forest decline in contrasting long-term
      chronosequences".

PMID- 15860611
TI  - Ecology. Synthesizing U.S. river restoration efforts.

PMID- 15860612
TI  - Applied physics. Toward bridging the terahertz gap with silicon-based lasers.

PMID- 15860613
TI  - Sociology. Network theory--the emergence of the creative enterprise.

PMID- 15860614
TI  - Ocean science. Ocean mixing in 10 steps.

PMID- 15860615
TI  - Structural biology. Nature's rotary electromotors.

PMID- 15860616
TI  - Neuroscience. Understanding intentions: through the looking glass.

PMID- 15860617
TI  - The influence of social hierarchy on primate health.
AB  - Dominance hierarchies occur in numerous social species, and rank within them can
      greatly influence the quality of life of an animal. In this review, I consider
      how rank can also influence physiology and health. I first consider whether it is
      high- or low-ranking animals that are most stressed in a dominance hierarchy;
      this turns out to vary as a function of the social organization in different
      species and populations. I then review how the stressful characteristics of
      social rank have adverse adrenocortical, cardiovascular, reproductive,
      immunological, and neurobiological consequences. Finally, I consider how these
      findings apply to the human realm of health, disease, and socioeconomic status.

PMID- 15860618
TI  - Horsfield's hawk-cuckoo nestlings simulate multiple gapes for begging.
AB  - Nestlings of some brood parasitic birds evict hosts' eggs and young soon after
      hatching, thereby avoiding discrimination by hosts while monopolizing parental
      care. Eviction carries a cost, however, because lone parasitic nestlings attract
      a reduced provisioning rate. Here we describe a form of visual signaling used by
      the evicting Horsfield's hawk-cuckoo (Cuculus fugax) to obtain sufficient food.
      The chick displays a gape-colored patch on the wing to the host parents as they
      deliver food, simulating the gaping display of more than one nestling.

PMID- 15860619
TI  - Structure of the rotor ring of F-Type Na+-ATPase from Ilyobacter tartaricus.
AB  - In the crystal structure of the membrane-embedded rotor ring of the sodium ion
      translocating adenosine 5'-triphosphate (ATP) synthase of Ilyobacter tartaricus
      at 2.4 angstrom resolution, 11 c subunits are assembled into an hourglass-shaped
      cylinder with 11-fold symmetry. Sodium ions are bound in a locked conformation
      close to the outer surface of the cylinder near the middle of the membrane. The
      structure supports an ion-translocation mechanism in the intact ATP synthase in
      which the binding site converts from the locked conformation into one that opens
      toward subunit a as the rotor ring moves through the subunit a/c interface.

PMID- 15860620
TI  - Parietal lobe: from action organization to intention understanding.
AB  - Inferior parietal lobule (IPL) neurons were studied when monkeys performed motor
      acts embedded in different actions and when they observed similar acts done by an
      experimenter. Most motor IPL neurons coding a specific act (e.g., grasping)
      showed markedly different activations when this act was part of different actions
      (e.g., for eating or for placing). Many motor IPL neurons also discharged during
      the observation of acts done by others. Most responded differentially when the
      same observed act was embedded in a specific action. These neurons fired during
      the observation of an act, before the beginning of the subsequent acts specifying
      the action. Thus, these neurons not only code the observed motor act but also
      allow the observer to understand the agent's intentions.

PMID- 15860621
TI  - Experimental verification of designer surface plasmons.
AB  - We studied the microwave reflectivity of a structured, near perfectly conducting
      substrate that was designed to verify the existence of a theoretically proposed
      new class of surface mode. Measurements of the mode's dispersion curve show that
      it correctly approaches the predicted asymptotic frequency; the curve also agrees
      well with that derived from a computer simulation. Modeling of the field
      distribution on resonance provides evidence of strong localization of the
      electric field at the interface and substantial power flow along the interface,
      thus verifying the surface plasmon-like nature of the mode.

PMID- 15860622
TI  - All-optical switching in rubidium vapor.
AB  - We report on an all-optical switch that operates at low light levels. It consists
      of laser beams counterpropagating through a warm rubidium vapor that induce an
      off-axis optical pattern. A switching laser beam causes this pattern to rotate
      even when the power in the switching beam is much lower than the power in the
      pattern. The observed switching energy density is very low, suggesting that the
      switch might operate at the single-photon level with system optimization. This
      approach opens the possibility of realizing a single-photon switch for quantum
      information networks and for improving transparent optical telecommunication
      networks.

PMID- 15860623
TI  - Early local last glacial maximum in the tropical Andes.
AB  - The local last glacial maximum in the tropical Andes was earlier and less
      extensive than previously thought, based on 106 cosmogenic ages (from beryllium
      10 dating) from moraines in Peru and Bolivia. Glaciers reached their greatest
      extent in the last glacial cycle approximately 34,000 years before the present
      and were retreating by approximately 21,000 years before the present, implying
      that tropical controls on ice volumes were asynchronous with those in the
      Northern Hemisphere. Our estimates of snowline depression reflect about half the
      temperature change indicated by previous widely cited figures, which helps
      resolve the discrepancy between estimates of terrestrial and marine temperature
      depression during the last glacial cycle.

PMID- 15860624
TI  - Laboratory earthquakes along inhomogeneous faults: directionality and supershear.
AB  - We report on the experimental observation of spontaneously nucleated ruptures
      occurring on frictionally held bimaterial interfaces with small amounts of wave
      speed mismatch. Rupture is always found to be asymmetric bilateral. In one
      direction, rupture always propagates at the generalized Rayleigh wave speed,
      whereas in the opposite direction it is subshear or it transitions to supershear.
      The lack of a preferred rupture direction and the conditions leading to
      supershear are discussed in relation to existing theory and to the earthquake
      sequence in Parkfield, California, and in North Anatolia.

PMID- 15860625
TI  - Enhanced diapycnal mixing by salt fingers in the thermocline of the tropical
      Atlantic.
AB  - Diapycnal mixing plays a significant role in the ocean's circulation and uptake
      of heat and carbon dioxide, but has not been quantified in salt finger-driven
      thermohaline staircases. We recently performed a tracer release experiment in the
      western tropical Atlantic staircase at approximately 400 m depth. The observed
      dispersion implies an effective diapycnal diffusivity for tracer and salt of 0.8
      to 0.9 x 10(-4) m2/s. Temperature microstructure data interpreted in terms of a
      vertical production-dissipation balance yields a smaller effective diffusivity
      for heat of 0.45 (+/- 0.2) x 10(-4) m2/s, consistent with salt fingers and well
      above the mixing ascribable to mechanical turbulence.

PMID- 15860626
TI  - Insect-resistant GM rice in farmers' fields: assessing productivity and health
      effects in China.
AB  - Although no country to date has released a major genetically modified (GM) food
      grain crop, China is on the threshold of commercializing GM rice. This paper
      studies two of the four GM varieties that are now in farm-level preproduction
      trials, the last step before commercialization. Farm surveys of randomly selected
      farm households that are cultivating the insect-resistant GM rice varieties,
      without the aid of experimental station technicians, demonstrate that when
      compared with households cultivating non-GM rice, small and poor farm households
      benefit from adopting GM rice by both higher crop yields and reduced use of
      pesticides, which also contribute to improved health.

PMID- 15860627
TI  - A rapid shift in a classic clinal pattern in Drosophila reflecting climate
      change.
AB  - Geographical clines in genetic polymorphisms are widely used as evidence of
      climatic selection and are expected to shift with climate change. We show that
      the classic latitudinal cline in the alcohol dehydrogenase polymorphism of
      Drosophila melanogaster has shifted over 20 years in eastern coastal Australia.
      Southern high-latitude populations now have the genetic constitution of more
      northerly populations, equivalent to a shift of 4 degrees in latitude. A similar
      shift was detected for a genetically independent inversion polymorphism, whereas
      two other linked polymorphisms exhibiting weaker clinal patterns have remained
      relatively stable. These genetic changes are likely to reflect increasingly
      warmer and drier conditions and may serve as sensitive biomarkers for climate
      change.

PMID- 15860628
TI  - PERIOD1-associated proteins modulate the negative limb of the mammalian circadian
      oscillator.
AB  - The clock proteins PERIOD1 (PER1) and PERIOD2 (PER2) play essential roles in a
      negative transcriptional feedback loop that generates circadian rhythms in
      mammalian cells. We identified two PER1-associated factors, NONO and WDR5, that
      modulate PER activity. The reduction of NONO expression by RNA interference
      (RNAi) attenuated circadian rhythms in mammalian cells, and fruit flies carrying
      a hypomorphic allele were nearly arrhythmic. WDR5, a subunit of histone
      methyltransferase complexes, augmented PER-mediated transcriptional repression,
      and its reduction by RNAi diminished circadian histone methylations at the
      promoter of a clock gene.

PMID- 15860629
TI  - Team assembly mechanisms determine collaboration network structure and team
      performance.
AB  - Agents in creative enterprises are embedded in networks that inspire, support,
      and evaluate their work. Here, we investigate how the mechanisms by which
      creative teams self-assemble determine the structure of these collaboration
      networks. We propose a model for the self-assembly of creative teams that has its
      basis in three parameters: team size, the fraction of newcomers in new
      productions, and the tendency of incumbents to repeat previous collaborations.
      The model suggests that the emergence of a large connected community of
      practitioners can be described as a phase transition. We find that team assembly
      mechanisms determine both the structure of the collaboration network and team
      performance for teams derived from both artistic and scientific fields.

PMID- 15860630
TI  - The dynamics of interhemispheric compensatory processes in mental imagery.
AB  - The capacity to generate and analyze mental visual images is essential for many
      cognitive abilities. We combined triple-pulse transcranial magnetic stimulation
      (tpTMS) and repetitive TMS (rTMS) to determine which distinct aspect of mental
      imagery is carried out by the left and right parietal lobe and to reveal
      interhemispheric compensatory interactions. The left parietal lobe was
      predominant in generating mental images, whereas the right parietal lobe was
      specialized in the spatial comparison of the imagined content. Furthermore, in
      case of an rTMS-induced left parietal lesion, the right parietal cortex could
      immediately compensate such a left parietal disruption by taking over the
      specific function of the left hemisphere.

PMID- 15860631
TI  - Not your father's postdoc.
AB  - In today's scientific labor market, just doing good science is no longer enough.
      Postdocs need realistic expectations, good information, and an entrepreneurial
      attitude toward their careers.

PMID- 15860632
TI  - Health problems of victims before and after disaster: a longitudinal study in
      general practice.
AB  - BACKGROUND: We aimed to quantify the health problems and to assess the possible
      risk factors for developing health problems in persons affected by the explosion
      of a firework depot at Enschede, The Netherlands, on May 13, 2000. The explosion
      considerably damaged buildings in the local neighbourhood and caused 22 immediate
      deaths and injuries in over 1000 people. METHODS: A longitudinal study of (89% of
      all) victims (n = 9329) and controls (n = 7392) with pre-disaster baseline
      morbidity for 16 months and post-disaster data for 2.5 years was conducted using
      the electronic medical records of general practitioners. Symptoms and diagnoses
      were recorded using the International Classification of Primary Care (ICPC).
      Prevalence rates for clusters of symptoms were compared between victim and
      control groups pre- and post-disaster. Risk factors for developing health
      problems were examined in hierarchical linear models. RESULTS: Two and a half
      years post-disaster, the prevalence of psychological problems in victims who had
      to relocate was about double and in the non-relocated victims one-third more than
      controls. Victims with pre-disaster psychological problems were at a greater risk
      for post-disaster psychological problems. Relocated victims showed an excess of
      medically unexplained physical symptoms (MUPS) especially in a period of
      increased media attention. Both groups of victims showed some increase of
      gastrointestinal (GI) morbidity 2.5 years post-disaster compared with their pre
      disaster rate, and compared with the control group. CONCLUSIONS: Two and a half
      years post-disaster an excess of psychological problems, MUPS, and
      gastrointestinal morbidity was observed. Pre-disaster psychological problems and
      inevitable relocation were predictors of more post-disaster psychological
      problems.

PMID- 15860633
TI  - Commentary: Advancing research into SES mechanisms that affect health.

PMID- 15860634
TI  - Thyroid cancer in Belarus.

PMID- 15860635
TI  - Contextual effect of income inequality on birth outcomes.
AB  - BACKGROUND: Though associations between income inequality and birth outcome have
      been suggested, mechanisms underlying this relationship are not known. In this
      analysis, we examined the relationship between income inequality and preterm
      birth (PTB) and post-neonatal mortality (PNM) to explore two potential mechanisms
      the proposed psychosocial stress and neo-material pathways. METHODS: Data on
      singleton births from 1998 to 2000 were obtained from the CDC's National Center
      for Health Statistics' Linked Birth and Infant Death files. The Gini Index was
      utilized to measure income inequality and was divided into tertiles representing
      high, medium, and low county-level inequality. To determine the association
      between the birth outcomes and county income inequality and to account for
      clustering within counties, we employed generalized estimating equation (GEE)
      modelling. RESULTS: PTB increased from 8.3% in counties with low income
      inequality to 10.0% in counties with high inequality. The Gini Index remained
      modestly associated with PTB after adjusting for individual level variables and
      mean county-level per capita income within the total population (AOR: 1.06; 95%
      CI 1.03-1.09) as well as within most of the racial/ethnic groups. PNM increased
      from 1.15 deaths per 1000 live births in low inequality counties to 1.32 in high
      inequality counties. However, after adjustment, income inequality was only
      associated with PNM within the non-Hispanic black population (AOR: 1.20; 95% CI
      1.03-1.39). CONCLUSIONS: These findings may provide some support for the
      association between income inequality and PTB. Further research is required to
      elucidate the biological mechanisms of income inequality.

PMID- 15860636
TI  - Medical and social reality in Chile.

PMID- 15860637
TI  - Commentary: Salvador Allende and the birth of Latin American social medicine.

PMID- 15860638
TI  - Commentary: Salvador Allende: his role in Chilean politics.

PMID- 15860639
TI  - Polyamine depletion inhibits irradiation-induced apoptosis in intestinal
      epithelia.
AB  - Our group has previously shown that polyamine depletion delays apoptosis in rat
      intestinal epithelial (IEC-6) cells (Ray RM, Viar MJ, Yuan Q, and Johnson LR, Am
      J Physiol Cell Physiol 278: C480-C489, 2000). Here, we demonstrate that polyamine
      depletion inhibits gamma-irradiation-induced apoptosis in vitro and in vivo.
      Pretreatment of IEC-6 cells with 5 mM alpha-difluoromethylornithine (DFMO) for 4
      days significantly reduced radiation-induced caspase-3 activity and DNA
      fragmentation. This protective effect was prevented by the addition of 10 muM
      exogenous putrescine. Radiation exposure to mice resulted in a high frequency of
      apoptosis over cells positioned fourth to seventh in crypt-villus units.
      Pretreatment of mice with 2% DFMO in drinking water significantly reduced
      apoptotic cells from approximately 2.75 to 1.61 per crypt-villus unit,
      accompanied by significant decreases in caspase-3 levels. Further examination
      showed that DFMO pretreatment inhibited the radiation-induced increase in the
      proapoptotic protein Bax. Moreover, DFMO pretreatment significantly enhanced the
      intestinal crypt survival rate by 2.1-fold subsequent to radiation and
      ameliorated mucosal structural damage. We conclude that polyamine depletion by
      DFMO inhibits gamma-irradiation-induced apoptosis of intestinal epithelial cells
      both in vitro and in vivo through inhibition of Bax and caspase-3 activity, which
      leads to attenuation of radiation-inflicted intestinal injury. These data
      indicate that DFMO may be therapeutically useful to counteract the
      gastrointestinal toxicity caused by chemoradiotherapy. This is the first
      demonstration that polyamines are required for apoptosis in vivo.

PMID- 15860640
TI  - Exposure to bacterial cell wall products triggers an inflammatory phenotype in
      hepatic stellate cells.
AB  - Activated hepatic stellate cells (HSCs) secrete extracellular matrix components
      during hepatic fibrosis, but recent studies have shown that HSCs can also release
      a variety of proinflammatory cytokines. Moreover, bacterial endotoxemia is not
      only associated with systemic complications in the late stages of liver failure
      but is also a direct cause of liver damage, activating resident inflammatory
      cells. In this study, we investigated whether HSCs can respond directly to
      bacterial cell wall products acquiring a new phenotype. RT-PCR and
      immunocytochemistry assays were used to show that murine HSCs expressed specific
      mRNA transcripts and proteins for LPS and lipoteichoic acid (LTA) receptor
      systems and peptidoglycan recognition proteins. Exposing HSCs to bacterial
      endotoxins led to phosphorylation of mitogen-activated protein kinase ERK1 and
      the development of a proinflammatory phenotype. After exposure to LPS, LTA, or N
      acetyl muramyl peptide, transforming growth factor-beta1, IL-6, and monocyte
      chemoattractant protein-1 (MCP-1) mRNA specific transcripts and proteins
      increased significantly in HSCs, as assayed by quantitative real-time RT-PCR and
      ELISA. These LPS-mediated effects in HSCs were receptor dependent, because LPS
      induced ERK1 phosphorylation, IL-6, and MCP-1 mRNA and protein level upregulation
      were significantly less pronounced in HSCs isolated from C3H/HeJ mice lacking
      Toll-like receptor 4. In conclusion, our results show that murine HSCs express
      functional receptors for bacterial endotoxins, and HSCs exposed to bacterial
      products develop a strong proinflammatory phenotype. We speculate that high
      levels of bacterial endotoxins in the portal vein may directly induce a
      proinflammatory phenotype in HSCs that contributes to liver damage.

PMID- 15860641
TI  - Retinoic acid formation from retinol in the human gastric mucosa: role of class
      IV alcohol dehydrogenase and its relevance to morphological changes.
AB  - Alcohol dehydrogenase (ADH) participates in the formation of retinoic acid from
      retinol in various organs including the gastric mucosa. However, its clinical
      significance still remains to be clarified. In this study, we identified the ADH
      isoforms responsible for the retinoic acid formation among various ADH isoforms
      and examined associations among the ADH activities, the retinoic acid formation
      level, and morphological changes in the human gastric mucosa. Human gastric
      samples were endoscopically obtained from 67 male subjects. Morphological changes
      were assessed by the Sydney system and activities of class I, III, and IV ADH
      isoforms were determined in each specimen. In 26 cases, levels of all-trans
      retinoic acid (ATRA) formation from all-trans retinol were examined. Among
      activities of the three ADH isoforms, class IV ADH activity was solely associated
      with the ATRA formation level. This association was found even when subjects' age
      and Helicobacter pylori infection status were adjusted. As the degrees of
      inflammation, atrophy, and intestinal metaplasia increased, the class IV ADH
      activity as well as the potential for the ATRA formation decreased. Class IV ADH
      is a major enzyme in the retinoic acid supply in the human gastric mucosa, and
      the reduction of its activity was associated with decreasing retinoic acid supply
      and progression of inflammation, atrophy, and intestinal metaplasia in the
      gastric mucosa. In that retinoic acid is a key molecule for maintaining normal
      morphology, the reduction of class IV ADH activity may be involved in the
      pathogenesis of these morphological changes in the human gastric mucosa.

PMID- 15860642
TI  - Cytokine-dependent regulation of hepatic organic anion transporter gene
      transactivators in mouse liver.
AB  - Proinflammatory cytokines such as TNF-alpha and IL-1beta lead to downregulation
      of hepatic organic anion transporters in cholestasis. This adapted response is
      transcriptionally mediated by nuclear hormone receptors and liver-specific
      transcription factors. Because little is known in vivo about cytokine-dependent
      regulatory events, mice were treated with either TNF-alpha or IL-1beta for up to
      16 h. Transporter mRNA expression was determined by Northern blot analysis,
      nuclear activity, and protein-expression of transactivators by EMSA and Western
      blotting. TNF-alpha induces a sustained decrease in Ntcp, Oatp1/Oatp1a1, and Bsep
      mRNA expression but exerts only transient [multidrug resistance-associated
      protein 2 (Mrp2)] or no effects (Mrp3) on Mrps. In addition to Ntcp and
      Oatp1/Oatp1a1, IL-1beta also downregulates Bsep, Mrp2, and Mrp3 mRNAs to some
      extent. To study transcriptional regulation, Ntcp and Bsep promoters were first
      cloned from mice revealing a new distal Ntcp hepatocyte nuclear factor 1 (HNF-1)
      element but otherwise show a conserved localization to known rat regulatory
      elements. Changes in transporter-expression are preceeded by a reduction in
      binding activities at IR-1, ER-8, DR-5, and HNF-1alpha sites after 4 h by either
      cytokine, which remained more sustained by TNF-alpha in the case of nuclear
      receptors. Nuclear protein levels of retinoid X receptor (RXR)-alpha are
      significantly decreased by TNF-alpha but only transiently affected by IL-1beta.
      Minor reductions of retinoic acid receptor, farnesoid X receptor, pregnane X
      receptor, and constitutive androstane receptor nuclear proteins are restricted to
      4 h after cytokine application and paralleled by a decrease in mRNA levels.
      Basolateral and canalicular transporter systems are downregulated by both
      cytokines, TNF-alpha and IL-1beta. Activity of HNF-1alpha as regulator of mNtcp
      is suppressed by both cytokines. Decreased binding activities of nuclear receptor
      heterodimers may be explained by a reduction of the ubiquitous heterodimerization
      partner RXR-alpha.

PMID- 15860643
TI  - Lack of pyloric interstitial cells of Cajal explains distinct peristaltic motor
      patterns in stomach and small intestine.
AB  - The frequency and propagation velocity of distension-induced peristaltic
      contractions in the antrum and duodenum are distinctly different and depend on
      activation of intrinsic excitatory motoneurons as well as pacemaker cells, the
      interstitial cells of Cajal associated with Auerbach's plexus (ICC-AP). Because
      ICC are critical for coordination of motor activities along the long axis of many
      regions in the gut, the role of ICC in antroduodenal coordination was
      investigated. We used immunohistochemistry, electron microscopy, simultaneous
      multiple electrical recordings in vitro, and videofluoroscopy in vivo in mice and
      rats. A strongly reduced number of ICC-AP with loss of network characteristics
      was observed in a 4-mm area in the rat and a 1-mm area in the mouse pyloric
      region. The pyloric region showed a slow wave-free gap of 4.1 mm in rats and 1.3
      mm in mice. Between antrum and duodenum, there was no interaction of electrical
      activities and in the absence of gastric emptying, there was no coordination of
      motor activities. When the pyloric sphincter opened, 2.4 s before the front of
      the antral wave reached the pylorus, the duodenum distended after receiving
      gastric content and aboral duodenal peristalsis was initiated, often disrupting
      other motor patterns. The absence of ICC-AP and slow wave activity in the pyloric
      region allows the antrum and duodenum to have distinct uncoordinated motor
      activities. Coordination of aborally propagating peristaltic antral and duodenal
      activity is initiated by opening of the pylorus, which is followed by distention
      induced duodenal peristalsis. Throughout this coordinated motor activity, the
      pacemaker systems in antrum and duodenum remain independent.

PMID- 15860644
TI  - Leptin enhances feeding suppression and neural activation produced by
      systemically administered bombesin.
AB  - Leptin amplifies feeding inhibition and neural activation produced by either
      cholecystokinin or intragastric preloads, suggesting that leptin may increase the
      efficacy of gastrointestinal meal-related signals. To determine whether leptin
      would similarly potentiate the feeding inhibitory actions of another putative
      satiety peptide, we evaluated the effects of third ventricular leptin
      administration on food intake and c-Fos activation in response to systemically
      administered bombesin (BN). Leptin (3.5 microg) was administered 1 h before
      either 0.9% saline or BN (0.32 and 1.0 nmol/kg) followed by 30-min access to
      Ensure liquid diet. Although neither leptin nor 0.32 nmol/kg BN alone suppressed
      Ensure intake, the combination reduced intake by 28%. The higher BN dose (1.0
      nmol/kg) produced a significant suppression by itself but was further enhanced in
      the presence of leptin. Consistent with the behavioral results, c-Fos activation
      in the nucleus of the solitary tract was increased by combined dosages of leptin
      and 0.32 nmol/kg BN beyond the individual response to either peptide. In the
      presence of leptin, BN produced a 3.4- to 5.2-fold increase in the number of c
      Fos-positive cells in the nucleus of the solitary tract compared with when BN was
      given alone. These data provide further support for the hypothesis that the
      effect of leptin on food intake may be mediated, in part, by modulating meal
      related satiety signals.

PMID- 15860645
TI  - Muscle Na-K-pump and fatigue responses to progressive exercise in normoxia and
      hypoxia.
AB  - To investigate the effects of hypoxia and incremental exercise on muscle
      contractility, membrane excitability, and maximal Na(+)-K(+)-ATPase activity, 10
      untrained volunteers (age = 20 +/- 0.37 yr and weight = 80.0 +/- 3.54 kg; +/- SE)
      performed progressive cycle exercise to fatigue on two occasions: while breathing
      normal room air (Norm; Fi(O(2)) = 0.21) and while breathing a normobaric hypoxic
      gas mixture (Hypox; Fi(O(2)) = 0.14). Muscle samples extracted from the vastus
      lateralis before exercise and at fatigue were analyzed for maximal Na(+)-K(+)
      ATPase (K(+)-stimulated 3-O-methylfluorescein phosphatase) activity in
      homogenates. A 32% reduction (P < 0.05) in Na(+)-K(+)-ATPase activity was
      observed (90.9 +/- 7.6 vs. 62.1 +/- 6.4 nmol.mg protein(-1).h(-1)) in Norm. At
      fatigue, the reductions in Hypox were not different (81 +/- 5.6 vs. 57.2 +/- 7.5
      nmol.mg protein(-1).h(-1)) from Norm. Measurement of quadriceps neuromuscular
      function, assessed before and after exercise, indicated a generalized reduction
      (P < 0.05) in maximal voluntary contractile force (MVC) and in force elicited at
      all frequencies of stimulation (10, 20, 30, 50, and 100 Hz). In general, no
      differences were observed between Norm and Hypox. The properties of the compound
      action potential, amplitude, duration, and area, which represent the
      electromyographic response to a single, supramaximal stimulus, were not altered
      by exercise or oxygen condition when assessed both during and after the
      progressive cycle task. Progressive exercise, conducted in Hypox, results in an
      inhibition of Na(+)-K(+)-ATPase activity and reductions in MVC and force at
      different frequencies of stimulation; these results are not different from those
      observed with Norm. These changes occur in the absence of reductions in
      neuromuscular excitability.

PMID- 15860646
TI  - Day- and nighttime injection of a nitric oxide synthase inhibitor elicits
      opposite sleep responses in rats.
AB  - Previous studies suggest that nitric oxide (NO) may play a role in sleep
      regulation, particularly in the homeostatic process. The present studies were
      undertaken to compare the sleep effects of injecting a NO synthase (NOS)
      inhibitor when homeostatic sleep pressure is naturally highest (light onset) or
      when it is at its nadir (dark onset) in rats. Sleep, electroencephalogram delta
      wave activity during nonrapid eye movement sleep (NREMS), also known as slow-wave
      activity (SWA), and brain temperature responses to three doses of the NOS
      inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME ; 5, 50, and 100 mg/kg)
      injected intraperitoneally at light or dark onset were examined in rats (n = 6 to
      8). The effects of 5 mg/kg L-NAME were determined in both normal and vagotomized
      (VX) rats. Light onset administration of 50 mg/kg L-NAME decreased NREMS amounts
      and suppressed SWA and increased rapid eye movement sleep (REMS) amounts. At dark
      onset, L-NAME injection also dose dependently suppressed SWA; however, unlike
      light onset injections, both NREMS and REMS amounts were increased after all
      three doses. Sleep responses to 5 mg/kg L-NAME were not different in control and
      VX rats, suggesting that the sleep effects of L-NAME are not mediated through the
      activation of sensory vagal mechanisms. The present findings suggest that timing
      of the injection is a major determinant of the sleep responses observed after
      systemic L-NAME injection in rats.

PMID- 15860647
TI  - Thermoregulatory responses of rats to conventional preparations of
      lipopolysaccharide are caused by lipopolysaccharide per se-- not by lipoprotein
      contaminants.
AB  - LPS preparations cause a variety of body temperature (T(b)) responses: monophasic
      fever, different phases of polyphasic fever, and hypothermia. Conventional (c)
      LPS preparations contain highly active lipoprotein contaminants (endotoxin
      proteins). Whereas LPS signals predominantly via the Toll-like receptor (TLR) 4,
      endotoxin proteins signal via TLR2. Several TLR2-dependent responses of
      immunocytes to cLPS in vitro are triggered by endotoxin proteins and not by LPS
      itself. We tested whether any T(b) response to cLPS from Escherichia coli 055:B5
      is triggered by non-TLR4-signaling contaminants. A decontaminated (d) LPS
      preparation (free of endotoxin proteins) was produced by subjecting cLPS to
      phenol-water reextraction. The presence of non-TLR4-signaling contaminants in
      cLPS (and their absence in dLPS) was confirmed by showing that cLPS (but not
      dLPS) induced IL-1beta expression in the spleen and increased serum levels of TNF
      alpha and IL-1beta of C3H/HeJ mice; these mice bear a nonfunctional TLR4. Yet,
      both cLPS and dLPS caused cytokine responses in C3H/HeOuJ mice; these mice bear a
      fully functional TLR4. We then studied the T(b) responses to cLPS and dLPS in
      Wistar rats preimplanted with jugular catheters. At a neutral ambient temperature
      (30 degrees C), a low (0.1 microg/kg iv) dose of cLPS caused a monophasic fever,
      whereas a moderate (10 microg/kg iv) dose produced a polyphasic fever. In the
      cold (20 degrees C), a high (500 microg/kg iv) dose of cLPS caused hypothermia.
      All T(b) responses to dLPS were identical to those of cLPS. We conclude that all
      known T(b) responses to LPS preparations are triggered by LPS per se and not by
      non-TLR4-signaling contaminants of such preparations.

PMID- 15860648
TI  - HIV protein, transactivator of transcription, alters circadian rhythms through
      the light entrainment pathway.
AB  - Patients infected with the human immunodeficiency virus (HIV), and other mammals
      infected with related lentiviruses, exhibit fatigue, altered sleep patterns, and
      abnormal circadian rhythms. A circadian clock in the hypothalamic suprachiasmatic
      nucleus (SCN) temporally regulates these functions in mammals. We found that a
      secretary HIV transcription factor, transactivator of transcription (Tat), resets
      the murine circadian clock, in vitro and in vivo, at clinically relevant
      concentrations (EC(50) = 0.31 nM). This effect of Tat occurs only during the
      subjective night, when N-methyl-D-aspartate (NMDA) receptor [D-2-amino-5
      phosphonovaleric acid (0.1 mM)] and nitric oxide synthase (N(G)-nitro-L-arginine
      methyl ester, 0.1 mM) inhibitors block Tat-induced phase shifts. Whole cell
      recordings of SCN neurons within the brain slice revealed that Tat did not
      activate NMDA receptors directly but potentiated NMDA receptor currents through
      the enhancement of glutamate release. Consistent with this presynaptic mechanism,
      inhibitors of neurotransmission block Tat-induced phase shifts, such as
      tetrodotoxin (1 microM), tetanus toxin (1 microM), P/Q/N type-calcium channel
      blockers (1 microM omega-agatoxin IVA and 1 microM omega-conotoxin GIVA) and
      bafilomycin A(1) (1 microM). Thus the effect of Tat on the SCN may underlie
      lentiviral circadian rhythm dysfunction by operating as a disease-dependent
      modulator of light entrainment through the enhancement of excitatory
      neurotransmission.

PMID- 15860649
TI  - Characterization of tetraethylammonium uptake across the basolateral membrane of
      the Drosophila Malpighian (renal) tubule.
AB  - Basolateral transport of the prototypical type I organic cation
      tetraethylammonium (TEA) by the Malpighian tubules of Drosophila melanogaster was
      studied using measurements of basolateral membrane potential (V(bl)) and uptake
      of [(14)C]-labeled TEA. TEA uptake was metabolically dependent and saturable
      (maximal rate of mediated TEA uptake by all potential transport processes,
      reflecting the total transport capacity of the membrane, 0.87 pmol.tubule(
      1).min(-1); concentration of TEA at 0.5 of the maximal rate of TEA uptake value,
      24 muM). TEA uptake in Malpighian tubules was inhibited by a number of type I
      (e.g., cimetidine, quinine, and TEA) and type II (e.g., verapamil) organic
      cations and was dependent on V(bl). TEA uptake was reduced in response to
      conditions that depolarized V(bl) (high-K(+) saline, Na(+)-free saline, NaCN) and
      increased in conditions that hyperpolarized V(bl) (low-K(+) saline). Addition of
      TEA to the saline bathing Malpighian tubules rapidly depolarized the V(bl),
      indicating that TEA uptake was electrogenic. Blockade of K(+) channels with
      Ba(2+) did not block effects of TEA on V(bl) or TEA uptake indicating that TEA
      uptake does not occur through K(+) channels. This is the first study to provide
      physiological evidence for an electrogenic carrier-mediated basolateral organic
      cation transport mechanism in insect Malpighian tubules. Our results also suggest
      that the mechanism of basolateral TEA uptake by Malpighian tubules is distinct
      from that found in vertebrate renal tubules.

PMID- 15860650
TI  - Persistence of sleep-temperature coupling after suprachiasmatic nuclei lesions in
      rats.
AB  - The suprachiasmatic nucleus (SCN) regulates the circadian rhythms of body
      temperature (T(b)) and vigilance states in mammals. We studied rats in which
      circadian rhythmicity was abolished after SCN lesions (SCNx rats) to investigate
      the association between the ultradian rhythms of sleep-wake states and brain
      temperature (T(br)), which are exposed after lesions. Ultradian rhythms of T(br)
      (mean period: 3.6 h) and sleep were closely associated in SCNx rats. Within each
      ultradian cycle, nonrapid eye movement (NREM) sleep was initiated 5 +/- 1 min
      after T(br) peaks, after which temperature continued a slow decline (0.02 +/-
      0.006 degrees C/min) until it reached a minimum. Sleep and slow wave activity
      (SWA), an index of sleep intensity, were associated with declining temperature.
      Cross-correlation analysis revealed that the rhythm of T(br) preceded that of SWA
      by 2-10 min. We also investigated the thermoregulatory and sleep-wake responses
      of SCNx rats and controls to mild ambient cooling (18 degrees C) and warming (30
      degrees C) over 24-h periods. SCNx rats and controls responded similarly to
      changes in ambient temperature. Cooling decreased REM sleep and increased wake.
      Warming increased T(br), blunted the amplitude of ultradian T(br) rhythms, and
      increased the number of transitions into NREM sleep. SCNx rats and controls had
      similar percentages of NREM sleep, REM sleep, and wake, as well as the same
      average T(b) within each 24-h period. Our results suggest that, in rats, the SCN
      modulates the timing but not the amount of sleep or the homeostatic control of
      sleep-wake states or T(b) during deviations in ambient temperature.

PMID- 15860651
TI  - White adipose tissue sensory nerve denervation mimics lipectomy-induced
      compensatory increases in adiposity.
AB  - The sensory innervation of white adipose tissue (WAT) is indicated by the
      labeling of sensory bipolar neurons in the dorsal root ganglion after retrograde
      dye placement into WAT. In addition, immunoreactivity (ir) for sensory-associated
      neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P in
      WAT pads also supports the notion of WAT sensory innervation. The function of
      this sensory innervation is unknown but could involve conveying the degree of
      adiposity to the brain. In tests of total body fat regulation, partial surgical
      lipectomy triggers compensatory increases in the mass of nonexcised WAT,
      ultimately resulting in restoration of total body fat levels in Siberian hamsters
      and other animals. The signal that triggers this compensation is unknown but
      could involve disruption of WAT sensory innervation that accompanies lipectomy.
      Therefore, a local and selective sensory denervation was accomplished by
      microinjecting the sensory nerve neurotoxin capsaicin bilaterally into epididymal
      WAT (EWAT) of Siberian hamsters, whereas controls received vehicle injections.
      Additional hamsters had bilateral EWAT lipectomy (EWATx) or sham lipectomy. As
      seen previously, EWATx resulted in significantly increased retroperitoneal WAT
      (RWAT) and inguinal WAT (IWAT) masses. Capsaicin treatment significantly
      decreased CGRP- but not tyrosine hydroxylase-ir, attesting to the diminished and
      selective sensory innervation. Capsaicin-treated hamsters also had increased RWAT
      and, to a lesser degree, IWAT mass largely mimicking the WAT mass increases seen
      after lipectomy. Collectively, these data suggest the possibility that
      information related to peripheral lipid stores may be conveyed to the brain via
      the sensory innervation of WAT.

PMID- 15860652
TI  - Differential acquisition of specific components of a classically conditioned
      arterial blood pressure response in rat.
AB  - Presenting a 15-s pulsed tone, the conditional stimulus (CS(+)), followed by 0.5
      s tail shock, to a well-trained rat causes a sudden, but transient, pressor
      response (C(1)). Blood pressure (BP) then drops before increasing again (C(2)). A
      steady tone of the same frequency never followed by a shock (a discriminative
      stimulus, or CS(-)) evokes a C(1) but not a C(2) response. Experiment 1 tested
      the hypothesis that this BP response pattern does not depend on the nature of the
      tone (i.e., pulsed vs. steady) used for CS(+) and CS(-). The tones were reversed
      from the traditional paradigm, above, in nine rats. The C(1) BP increase for a
      steady-tone CS(+) (+4.8 +/- 1.9 mmHg, mean change +/- SE) and a pulsed CS(-)
      (+2.9 +/- 1.3 mmHg) did not differ. Conversely, C(2) showed a clear
      discrimination (CS(+): +5.1 +/- 1.2 mmHg, CS(-): +0 .7 +/- 0.8 mmHg; P < 0.05).
      Experiment 2 tested the hypothesis that the C(1) and C(2) BP responses first
      appear at different times during training. On training day 1, five 15-s pulsed
      tones (CS(+)) were presented to each of 18 rats; the last tone was followed by a
      tail shock. Likewise, five steady CS(-) tones never followed by shock were given.
      Training continued for 2 more days, with each CS(+) followed by shock. At the end
      of day 2, CS(+) evoked a C(1) BP response (+3.9 +/- 0.9 mmHg) but no C(2) (+0.6
      +/- 0.4 mmHg, not significant vs. pretone). By the end of day 3, CS(+) evoked a
      significant (vs. baseline) C(1) (+7.3 +/- 1.4 mmHg) and C(2) (+3.3 +/- 0.8 mmHg).
      Conversely, although CS(-) evoked a C(1) response (3.5 +/- 1.3 mmHg), there was
      no C(2) (+0.7 +/- 0.5 mmHg; not significant). We conclude that 1) C(1) and C(2)
      are acquired at different rates, 2) early in training C(1) is an orienting
      response evoked by both tones, and 3) C(2) is only acquired as an animal learns
      to associate the CS(+) tone with shock. This suggests that C(1) and C(2) are
      controlled by different processes in the brain.

PMID- 15860653
TI  - Functional analysis of six human aryl hydrocarbon receptor variants in a Japanese
      population.
AB  - Aryl hydrocarbon receptor (AhR) is an important transcriptional regulator
      involved in the induction of CYP1A1, CYP1A2, CYP1B1, UGT1A1, and UGT1A6. In this
      study, functional properties of four novel naturally occurring human AhR variants
      (K401R, N487D, I514T, and K17T/R554K) were examined along with the single
      variants K17T and R554K. The luciferase reporter assay using the CYP1A1 promoter
      reporter in HeLa cells treated with beta-naphthoflavone or 3-methylcholanthrene,
      which are known as typical agonists for AhR, showed that reporter activities of
      the K401R and N487D variants were reduced to 40 to 58% of those of wild-type (WT)
      but not of the other variants. Similarly, the K401R and N487D variants also
      reduced the omeprazole-induced reporter activities to approximately 56 and 74% of
      those of the WT, respectively. The reduced activities of the two variants were
      probably caused by the reduced protein expression levels, since the protein
      levels of the K401R and N487D variants were approximately 52 and 47% of the WT,
      respectively, without any changes in their mRNA levels. The reduced protein
      levels were recovered by treatment with a proteasome inhibitor MG132 [N
      benzoyloxycarbonyl (Z)-Leu-Leu-leucinal], suggesting that the reduced protein
      levels were caused by the accelerated proteasomal degradation by a proteasome.
      Together, the current data demonstrate that the K401R and N487D variants reduce
      their apparent transcriptional activities, both ligand-induced and omeprazole
      induced activation, probably through reduced protein expression. Thus, these two
      variants may influence drug metabolism through reduced induction of CYP1A1 and
      other target enzymes.

PMID- 15860654
TI  - Neuropharmacokinetics of a new alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid (AMPA) modulator, S18986 [(S)-2,3-dihydro-[3,4]cyclopentano-1,2,4
      benzothiadiazine-1,1-dioxide], in the rat.
AB  - The aim of our study was to determine the neuropharmacokinetics of S18986 [(S)
      2,3-dihydro-[3,4]cyclopentano-1,2,4-benzothiadiazine-1,1-dioxide], a new positive
      allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      type receptors, in the rat. We focused on its blood-brain barrier (BBB) uptake
      and on its brain intra- and extracellular fluid (bICF-bECF) partitioning. BBB
      transport of S18986 was measured using the in situ brain perfusion technique.
      bECF concentrations were determined by microdialysis in the two effector areas,
      i.e., frontal cortex (FC) and dorsal hippocampus (DH), and blood samples were
      collected simultaneously through a femoral catheter. Cerebrospinal fluid and
      brain tissue concentrations were determined using a conventional pharmacokinetic
      approach. Using all the experimental data, pharmacokinetic modeling was applied
      to describe the S18986 blood-brain disposition. The brain uptake clearance of
      S18986 was found to be high, about 20 mul s(-1) g(-1). Terminal half-lives were
      similar in plasma and brain, at around 1 h. Experimental and predicted blood and
      brain concentrations were a good fit with the pharmacokinetic model, which
      assumed first-order rate constants at each interface. Ratios of bECF to the
      unbound plasma area under the curve (AUC) were 0.24 in FC and 0.25 in DH, whereas
      ratios of bICF/plasma AUC were 1 in FC and 1.5 in DH. We conclude that despite
      the ratio of bECF/plasma AUC below 1, there is nevertheless an elevated BBB
      uptake of S18986. This can be explained by the S18986 nonhomogenous bECF/bICF
      partitioning, since S18986 mainly distributes into hippocampal bICF. This
      illustrates the importance of taking bECF/bICF partitioning into account when
      interpreting the neuropharmacokinetics of a drug.

PMID- 15860655
TI  - Automated screening with confirmation of mechanism-based inactivation of CYP3A4,
      CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes.
AB  - A strategy is proposed to profile compounds for mechanism-based inactivation of
      CYP3A4, CYP2C19, CYP2C9, CYP2D6, and CYP1A2 based on an apparent partition ratio
      screen. Potent positives from the screen are confirmed by time- and concentration
      dependent inactivation assays. Quasi-irreversible inhibitions are then
      differentiated from irreversible inactivations by oxidation with potassium
      ferricyanide and/or dialysis. The three-step screening procedure has been
      validated with acceptable accuracy and precision for detection and confirmation
      of mechanism-based inactivators in drug discovery. We report here the apparent
      partition ratios for 19 mechanism-based inactivators and four quasi-irreversible
      inhibitors obtained under the same experimental conditions. The apparent
      partition ratio screen was automated to provide throughput for determining
      structure-mechanism-based inactivation relationships. Information about
      reversibility can be used to assess potential toxicity mediated by covalent
      adducts, as well as the potential for pharmacokinetic drug-drug interactions.
      Direct comparison of known mechanism-based inactivators and quasi-irreversible
      inhibitors, based on our screening of apparent partition ratios, has identified
      ritonavir, mibefradil, and azamulin as highly effective mechanism-based
      inactivators; e.g., 1 mol of CYP3A4 was inactivated on turnover of about 2 mol of
      compound. Other mechanism-based inactivators we identified include bergamottin
      (CYP1A2 besides previously reported CYP3A4), troglitazone (CYP3A4), rosiglitazone
      (CYP3A4), and pioglitazone (CYP3A4). Comparison of the apparent partition ratios
      and inactivation clearance data for the three glitazones suggests that the
      chromane moiety on troglitazone contributes to its greater potency for mechanism
      based inactivation.

PMID- 15860656
TI  - Multiple mechanisms are involved in the biliary excretion of acetaminophen
      sulfate in the rat: role of Mrp2 and Bcrp1.
AB  - Previous reports have demonstrated that sulfate metabolites may be excreted into
      bile by the multidrug resistance-associated protein 2 (Mrp2, Abcc2). Although
      recombinant human breast cancer resistance protein (BCRP, ABCG2) has affinity for
      sulfated xenobiotics and endobiotics, its relative importance in biliary
      excretion of sulfate metabolites in the intact liver is unknown. In the present
      studies, the potential contribution of Bcrp1 to the biliary excretion of
      acetaminophen sulfate (AS) was examined following acetaminophen administration
      (66 micromol, bolus) to isolated perfused livers (IPLs) from wild-type Wistar and
      Mrp2-deficient (TR(-)) Wistar rats in the presence or absence of the Bcrp1 and P
      glycoprotein inhibitor, GF120918 [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2
      isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine
      carboxamide]. Recovery of AS in bile of TR(-) rat livers was approximately 5-fold
      lower relative to wild-type controls (0.3 +/- 0.1 versus 1.5 +/- 0.3 micromol).
      In the presence of GF120918, biliary excretion of AS was decreased approximately
      2-fold in both TR(-) (0.16 +/- 0.09 micromol) and wild-type (0.8 +/- 0.3
      micromol) rat IPLs. These changes were primarily due to alterations in the rate
      constant governing biliary excretion of AS, which was decreased approximately 90%
      in TR(-) relative to wild-type rat IPLs (0.02 +/- 0.01 versus 0.2 +/- 0.1 h(-1))
      and was further decreased in the presence of GF120918 (0.010 +/- 0.003 and 0.12
      +/- 0.05 h(-1); TR(-) and wild-type, respectively). In vitro assays indicated
      that impaired AS biliary excretion in the presence of GF120918 was due to
      inhibition of Bcrp1, and not P-glycoprotein. In conclusion, Mrp2 and, to a lesser
      extent, Bcrp1 mediate biliary excretion of AS in the intact liver.

PMID- 15860657
TI  - Nicotine 5'-oxidation and methyl oxidation by P450 2A enzymes.
AB  - In smokers, the primary pathway of nicotine metabolism is P450 2A6-catalyzed 5'
      oxidation. The nicotine Delta(5'(1'))-iminium ion product of this reaction is
      further metabolized to cotinine by aldehyde oxidase. Previous investigators have
      reported kinetic parameters for cotinine formation using human liver cytosol as a
      source of aldehyde oxidase. Using [5-(3)H]nicotine and radioflow high-performance
      liquid chromatography analysis, we determined kinetic parameters for nicotine 5'
      oxidation by P450 2A6 and the closely related human extrahepatic P450 2A13 as
      well as the rodent P450s 2A3, 2A4, and 2A5. The formation of both cotinine and
      nicotine Delta(5'(1'))-iminium ion was monitored. The K(m) and V(max) values for
      P450 2A6 were 144 +/- 15 muM and 1.30 +/- 0.05 pmol/min/pmol, respectively.
      Previously reported K(m) values for cotinine formation by P450 2A6 in the
      presence of cytosol were much lower, ranging from 11 to 45 muM. P450 2A13 was a
      somewhat better catalyst of nicotine Delta(5'(1'))-iminium formation, with 2-fold
      lower K(m) and 2-fold higher V(max) values than P450 2A6. The rat P450 2A3 and
      the mouse P450 2A5, which are 85 and 84% identical to P450 2A6, were much more
      efficient catalysts of nicotine 5'-oxidation. P450 2A4 was not an efficient
      catalyst of nicotine metabolism. Whereas 5'-oxidation was the major pathway of
      nicotine metabolism for all five P450 2A enzymes, these enzymes also catalyzed
      methyl oxidation. Nornicotine, the product of this reaction was detected as 5 to
      15% of the total nicotine metabolites. Nornicotine is the amine precursor to the
      esophageal carcinogen N'-nitrosonornicotine. Therefore, methyl oxidation of
      nicotine by P450 2A6 or P450 2A13 followed by nitrosation of nornicotine are
      possible endogenous pathways of N'-nitrosonornicotine formation.

PMID- 15860658
TI  - Betamethasone pharmacokinetics after two prodrug formulations in sheep:
      implications for antenatal corticosteroid use.
AB  - Maternal administration of betamethasone to enhance fetal lung maturation for
      women who threaten preterm labor is common clinical practice. However,
      recommendations regarding the choice of betamethasone formulations for perinatal
      use are vague. The disposition of betamethasone from two commonly used antenatal
      formulations is poorly understood. We therefore designed a study to capture the
      true pharmacokinetic profiles of betamethasone from these fast acting and dual
      release formulations. Betamethasone in sheep plasma was measured by a newly
      designed, highly sensitive liquid chromatography/tandem mass spectrometry assay
      after intramuscular injection (n = 4) of 0.25 mg/kg betamethasone phosphate and
      0.5 mg/kg betamethasone phosphate/acetate formulations. Compartmental modeling
      was performed using the ADAPT II program. Betamethasone pharmacokinetics could be
      captured for 24 h for the phosphate and for 5 days for the phosphate/acetate
      formulations. The phosphate formulation profile had the appearance of a
      traditional Bateman function with a terminal half-life of 4 h, whereas the
      phosphate/acetate formulation produced a biexponential decline with a terminal
      half-life of 14 h. The latter is much longer than is commonly reported and has
      been missed in the literature due to assay limitations. Extrapolations to humans
      indicate that although both formulations might have similar therapeutic indices,
      the dual formulation might be associated with a lower safety profile. In light of
      this newly identified long terminal half-life for the betamethasone dual
      formulation, dosing practices for betamethasone in pregnancy need to be
      reassessed.

PMID- 15860659
TI  - Sp1 and Sp3 regulate basal transcription of the human CYP2F1 gene.
AB  - Selective transcription of the human CYP2F1 gene in lung tissues may control the
      susceptibilities of this organ to diverse pneumotoxicants and lung carcinogens.
      However, the mechanisms responsible for CYP2F1 organ-selective transcription have
      not been elucidated. The objectives of the current studies were to identify and
      characterize basal transcription elements within the TATA-less promoter region of
      CYP2F1. Four putative Sp1-like sites were identified in the CYP2F1 promoter.
      Competitive electrophoretic mobility shift assay analysis with mutated
      oligonucleotide probes and lung A549 cell nuclear extract, along with supershift
      studies using antibodies to either Sp1 or Sp3 proteins, demonstrated that all
      four sites formed three specific protein-DNA complexes. Mutations in any of the
      four core Sp1-like motifs abolished protein-DNA binding. Western blot analysis of
      both human tissues and cells showed that Sp1 was considerably higher in lung than
      liver and that Sp3 was much higher in liver than lung. Promoter activation of a
      luciferase reporter construct was sequentially increased by addition of each of
      the four Sp1-like motifs in lung A549 cells but not in liver HepG2 cells.
      Cotransfection of a Sp1 expression vector with the reporter construct
      dramatically increased luciferase activity in either A549 cells or Sp1-deficient
      Drosophila Schneider line 2 (SL-2) cells. However, similar cotransfections with
      an Sp3 expression vector failed to increase activity. Cotransfection of both the
      Sp1 and Sp3 expression vectors considerably decreased Sp1-mediated activity in
      A549 cells and abolished activity in SL-2 cells. Thus, these studies demonstrated
      that four Sp1-dependent proximal promoter elements drive organ-selective CYP2F1
      gene transcription, and that Sp1 and Sp3 factors interact to modulate
      constitutive CYP2F1 transcription in lung cells.

PMID- 15860660
TI  - Identification of 2 major loci linked to autoimmune hemolytic anemia in NZB mice.
AB  - Using a cohort of C57BL/6 (B6) x (NZB x B6)F1 backcross male mice bearing the Yaa
      (Y-linked autoimmune acceleration) mutation, we mapped and characterized the NZB
      derived susceptibility loci predisposing to the development of autoimmune
      hemolytic anemia (AHA). Our analysis identified 2 major loci on NZB chromosome 7
      and chromosome 1 linked with Coombs antierythrocyte autoantibody production, and
      their contributions were confirmed by the analysis of B6.Yaa mice (B6 mice
      bearing the Yaa mutation) congenic for each NZB-derived susceptibility interval.
      A newly identified Aia3 (autoimmune anemia 3) locus present on NZB chromosome 7
      selectively regulated Coombs antibody responses, while the second locus, directly
      overlapping with Nba2 (NZB autoimmunity 2) on chromosome 1, promoted the
      development of AHA, likely as part of its effect on overall production of lupus
      autoantibodies. A higher incidence of Coombs antibody production in B6.Aia3
      congenic mice (B6 mice bearing the NZB-Aia3 locus) than B6.Nba2 mice (B6 mice
      bearing the NZB-Nba2 locus) indicated a major role for Aia3 in AHA. Notably, lack
      of expansion of B1 cells in B6.Aia3 congenic mice argued against the involvement
      of this subset in AHA. Finally, our analysis of BC mice also demonstrated the
      presence of a B6-derived H2-linked locus on chromosome 17 that apparently
      regulated the production of Coombs antibodies as a result of its overall
      autoimmune promoting effect.

PMID- 15860661
TI  - The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both
      "atypical" myeloproliferative disorders and myelodysplastic syndromes.
AB  - A somatic mutation in the JH2 autoinhibitory domain of the Janus kinase 2 (JAK2)
      tyrosine kinase was recently described in polycythemia vera, essential
      thrombocythemia, and myelofibrosis with myeloid metaplasia. The prevalence of
      this mutation in either "atypical" myeloproliferative disorders (MPDs) or the
      myelodysplastic syndromes (MDSs) is unknown. Bone marrow-derived genomic DNA from
      245 patients--119 with chronic myelomonocytic leukemia (CMML), 101 with MDS, 11
      with hypereosinophilic syndrome (HES), 8 with systemic mastocytosis (SM), and 6
      with chronic neutrophilic leukemia (CNL)--was screened for the JAK2 V617F
      mutation. A mutant allele was detected in 11 patients: 3 with CMML (3%), 5 with
      MDS (5%), 2 with SM, and 1 with CNL. Interestingly, one of the patients with SM
      and the patient with CNL with JAK2 V617F had a history of lymphoma, and this
      patient with SM also had associated myelofibrosis and CMML. The current
      observation strengthens the specific association between JAK2 V617F and classic
      MPD, but also suggests an infrequent occurrence in other myeloid disorders.

PMID- 15860662
TI  - Plasma chemokine levels correlate with the outcome of antiviral therapy in
      patients with hepatitis C.
AB  - Chronic infection with the hepatitis C virus (HCV) is associated with failures of
      T-cell-mediated immune clearance and with abnormal B-cell growth and activation.
      We examined the levels of chemokines that bind to CXC chemokine receptor 3
      (CXCR3) to determine whether such chemokines might play a role in the failure of
      the immune system to clear HCV infection. Elevations in CXC ligand 9 (CXCL9),
      CXCL10, and CXCL11 were observed in all patients with HCV. CXCR3 expression was
      increased significantly on peripheral blood B lymphocytes, but not T lymphocytes,
      from individuals with HCV infection. Chemokine levels were measured in samples
      collected before, during, and after antiviral therapy from a group of 29 patients
      infected with HCV genotypes 1a (24 patients) and 1b (5 patients). Levels of
      CXCL10 and CXCL9 decreased following successful antiviral therapy; CXCL11 did not
      decline significantly during or in the first 6 months after therapy. The baseline
      level of CXCL10 (measured before the start of antiviral treatment) was greatest
      in patients with HCV who subsequently became nonresponders to therapy. These
      results suggest that plasma concentrations of immunoreactive CXCL10 may be a
      predictor of responsiveness or nonresponsiveness to antiviral therapy with
      pegylated interferon (IFN) with or without ribavirin. This observation has
      implications for understanding the pathogenesis of HCV infection.

PMID- 15860663
TI  - Resistance to farnesyltransferase inhibitors in Bcr/Abl-positive lymphoblastic
      leukemia by increased expression of a novel ABC transporter homolog ATP11a.
AB  - Resistance to cytotoxic drugs frequently emerges during treatment of leukemia
      with conventional chemotherapy. New classes of anticancer drugs, such as the
      farnesyltransferase inhibitors (FTIs), show therapeutic promise, but whether
      cells will easily develop resistance against them is not known. Here, we grew
      breakpoint cluster region/Abelson murine leukemia (Bcr/Abl) P190 lymphoblasts on
      stroma and made them resistant to the FTI SCH66336/lonafarnib to model emerging
      drug resistance in a patient. These cells exhibited greatly increased (> 100
      fold) expression levels of a novel ATP (adenosine triphosphate)-binding cassette
      (ABC) transporter-homologous gene, ATP11A. We showed that overexpression of this
      gene provided protection against the effects of SCH66336, whereas knockdown of
      endogenous ATP11a using small interfering RNA (siRNA) made cells more sensitive
      to this drug. The lymphoblasts that were resistant to this FTI were also more
      resistant to FTI-276 and to GGTI-298, 2 other structurally similar inhibitors.
      Surprisingly, the cells were also able to survive higher concentrations of
      imatinib mesylate, the Bcr/Abl tyrosine kinase inhibitor. However, the cells
      remained sensitive to vincristine. Our results show that elevated levels of
      ATP11a can protect malignant lymphoblastic leukemia cells against several novel
      small molecule signal transduction inhibitors. A determination of the expression
      levels of this gene may have prognostic value when treatment with such classes of
      drugs is contemplated.

PMID- 15860664
TI  - The Shwachman-Diamond SBDS protein localizes to the nucleolus.
AB  - Shwachman-Diamond syndrome (SDS) is an autosomal recessively inherited disorder
      characterized by exocrine pancreatic insufficiency and bone marrow failure. The
      gene for this syndrome, SBDS, encodes a highly conserved novel protein. We
      characterized Shwachman-Bodian-Diamond syndrome (SBDS) protein expression and
      intracellular localization in 7 patients with SDS and healthy controls. As
      predicted by gene mutation, 4 patients with SDS exhibited no detectable full
      length SBDS protein. Patient DF277, who was homozygous for the IVS2 + 2 T>C
      splice donor mutation, expressed scant levels of SBDS protein. Patient SD101
      expressed low levels of SBDS protein harboring an R169C missense mutation.
      Patient DF269, who carried no detectable gene mutations, expressed wild-type
      levels of SBDS protein to add further support to the growing body of evidence for
      additional gene(s) that might contribute to the pathogenesis of the disease
      phenotype. The SBDS protein was detected in both the nucleus and the cytoplasm of
      normal control fibroblasts, but was particularly concentrated within the
      nucleolus. SBDS localization was cell-cycle dependent, with nucleolar
      localization during G1 and G2 and diffuse nuclear localization during S phase.
      SBDS nucleolar localization was intact in SD101 and DF269. The intranucleolar
      localization of SBDS provides further supportive evidence for its postulated role
      in rRNA processing.

PMID- 15860665
TI  - Differential requirements for the activation domain and FOG-interaction surface
      of GATA-1 in megakaryocyte gene expression and development.
AB  - GATA1 is mutated in patients with 2 different disorders. First, individuals with
      a GATA1 mutation that blocks the interaction between GATA-1 and its cofactor
      Friend of GATA-1 (FOG-1) suffer from dyserythropoietic anemia and
      thrombocytopenia. Second, children with Down syndrome who develop acute
      megakaryoblastic leukemia harbor mutations in GATA1 that lead to the exclusive
      expression of a shorter isoform named GATA-1s. To determine the effect of these
      patient-specific mutations on GATA-1 function, we first compared the gene
      expression profile between wild-type and GATA-1-deficient megakaryocytes. Next,
      we introduced either GATA-1s or a FOG-binding mutant (V205G) into GATA-1
      deficient megakaryocytes and assessed the effect on differentiation and gene
      expression. Whereas GATA-1-deficient megakaryocytes failed to undergo terminal
      differentiation and proliferated excessively in vitro, GATA-1s-expressing cells
      displayed proplatelet formation and other features of terminal maturation, but
      continued to proliferate aberrantly. In contrast, megakaryocytes that expressed
      V205G GATA-1 exhibited reduced proliferation, but failed to undergo maturation.
      Examination of the expression of megakaryocyte-specific genes in the various
      rescued cells correlated with the observed phenotypic differences. These studies
      show that GATA-1 is required for both normal regulation of proliferation and
      terminal maturation of megakaryocytes, and further, that these functions can be
      uncoupled by mutations in GATA1.

PMID- 15860666
TI  - [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in
      aggressive lymphoma: an early prognostic tool for predicting patient outcome.
AB  - Assessment of early therapeutic response using metabolic imaging is potentially
      useful to determine prognosis in aggressive lymphoma. Between January 2000 and
      January 2004, 90 patients with newly diagnosed aggressive lymphoma (median age 53
      years, 94% diffuse large B-cell) were prospectively explored with [18F]fluoro-2
      deoxy-D-glucose positron emission tomography (FDG-PET) prior to induction
      chemotherapy, after 2 cycles ("early PET"), and after induction completion.
      Therapeutic response was evaluated using conventional diagnostic methods at 4
      cycles. Induction treatment with an anthracycline-containing regimen was
      administered to all patients, associated with rituximab in 41%. According to the
      International Prognostic Index (IPI), 37 patients and 53 patients belonged to the
      lower- and higher-risk groups, respectively. At midinduction, "early PET" was
      considered negative in 54 patients and positive in 36. After completion of
      induction, 83% of PET-negative patients achieved complete remission compared with
      only 58% of PET-positive patients. Outcome differed significantly between PET
      negative and PET-positive groups; the 2-year estimates of event-free survival
      reached 82% and 43%, respectively (P < .001), and the 2-year estimates of overall
      survival reached 90% and 61%, respectively (P = .006). Predictive value of "early
      PET" was observed in both the lower-risk and higher-risk groups, indicating
      prognostic independence from the IPI. Therefore, FDG-PET should be an early guide
      to first-line strategies in aggressive lymphoma.

PMID- 15860667
TI  - Transcriptional induction of cyclooxygenase-2 in osteoclast precursors is
      involved in RANKL-induced osteoclastogenesis.
AB  - Regulation of osteoclast differentiation is key to understanding the pathogenesis
      and to developing treatments for bone diseases such as osteoporosis. To gain
      insight into the mechanism of the receptor activator of nuclear factor (NF)
      kappaB ligand (RANKL)-specific induction of the osteoclast differentiation
      program, we took a suppression-subtractive hybridization screening approach to
      identify genes specifically induced via the RANKL-Rac1 signaling pathway. Among
      identified targets, we show that RANKL selectively induces cyclooxygenase (COX) 2
      expression via Rac1 that results in turn in production of prostaglandin E2 (PGE2)
      in RAW 264.7 cells. By using transient transfection assays, we found that the 
      233/-206 region of the COX-2 promoter gene was critical for RANKL-induced
      promoter activity. This RANKL-responsive region contained an NF-kappaB site that,
      when mutated, completely abolished the induction of NF-kappaB DNA-binding
      activity by RANKL. Blockade of COX-2 by celecoxib inhibits differentiation of
      bone marrow-derived monocyte/macrophage precursor cells (BMMs) into tartrate
      resistant acid phosphatase-positive (TRAP+) osteoclastic cells. This inhibition
      can be rescued by the addition of exogenous PGE2, suggesting that COX-2-dependent
      PGE2 induction by RANKL in osteoclast precursors is required for osteoclast
      differentiation.

PMID- 15860668
TI  - Infection of human CD34+ progenitor cells with Bartonella henselae results in
      intraerythrocytic presence of B. henselae.
AB  - Although there is evidence that endothelial cells are important targets for human
      pathogenic Bartonella species, the primary niche of infection is unknown. Here we
      elucidated whether human CD34+ hematopoietic progenitor cells (HPCs) internalize
      B. henselae and may serve as a potential niche of the pathogen. We showed that B.
      henselae does not adhere to or invade human erythrocytes. In contrast, B.
      henselae invades and persists in HPCs as shown by gentamicin protection assays,
      confocal laser scanning microscopy (CLSM), and electron microscopy (EM).
      Fluorescence-activated cell sorting (FACS) analysis of glycophorin A expression
      revealed that erythroid differentiation of HPCs was unaffected following
      infection with B. henselae. The number of intracellular B. henselae continuously
      increased over a 13-day period. When HPCs were infected with B. henselae
      immediately after isolation, intracellular bacteria were subsequently detectable
      in differentiated erythroid cells on day 9 and day 13 after infection, as shown
      by CLSM, EM, and FACS analysis. Our data provide, for the first time, evidence
      that a bacterial pathogen is able to infect and persist in differentiating HPCs,
      and suggest that HPCs might serve as a potential primary niche in Bartonella
      infections.

PMID- 15860669
TI  - Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human
      dendritic cells.
AB  - Lymphopenia and increasing viral load in the first 10 days of severe acute
      respiratory syndrome (SARS) suggested immune evasion by SARS-coronavirus (CoV).
      In this study, we focused on dendritic cells (DCs) which play important roles in
      linking the innate and adaptive immunity. SARS-CoV was shown to infect both
      immature and mature human monocyte-derived DCs by electron microscopy and
      immunofluorescence. The detection of negative strands of SARS-CoV RNA in DCs
      suggested viral replication. However, no increase in viral RNA was observed.
      Using cytopathic assays, no increase in virus titer was detected in infected DCs
      and cell-culture supernatant, confirming that virus replication was incomplete.
      No induction of apoptosis or maturation was detected in SARS-CoV-infected DCs.
      The SARS-CoV-infected DCs showed low expression of antiviral cytokines
      (interferon alpha [IFN-alpha], IFN-beta, IFN-gamma, and interleukin 12p40 [IL
      12p40]), moderate up-regulation of proinflammatory cytokines (tumor necrosis
      factor alpha [TNF-alpha] and IL-6) but significant up-regulation of inflammatory
      chemokines (macrophage inflammatory protein 1alpha [MIP-1alpha], regulated on
      activation normal T cell expressed and secreted [RANTES]), interferon-inducible
      protein of 10 kDa [IP-10], and monocyte chemoattractant protein 1 [MCP-1]). The
      lack of antiviral cytokine response against a background of intense chemokine up
      regulation could represent a mechanism of immune evasion by SARS-CoV.

PMID- 15860670
TI  - MRI R2 and R2* mapping accurately estimates hepatic iron concentration in
      transfusion-dependent thalassemia and sickle cell disease patients.
AB  - Measurements of hepatic iron concentration (HIC) are important predictors of
      transfusional iron burden and long-term outcome in patients with transfusion
      dependent anemias. The goal of this work was to develop a readily available,
      noninvasive method for clinical HIC measurement. The relaxation rates R2 (1/T2)
      and R2* (1/T2*) measured by magnetic resonance imaging (MRI) have different
      advantages for HIC estimation. This article compares noninvasive iron estimates
      using both optimized R2 and R2* methods in 102 patients with iron overload and 13
      controls. In the iron-overloaded group, 22 patients had concurrent liver biopsy.
      R2 and R2* correlated closely with HIC (r2 > or = .95) for HICs between 1.33 and
      32.9 mg/g, but R2 had a curvilinear relationship to HIC. Of importance, the R2
      calibration curve was similar to the curve generated by other researchers,
      despite significant differences in technique and instrumentation. Combined R2 and
      R2* measurements did not yield more accurate results than either alone. Both R2
      and R2* can accurately measure hepatic iron concentration throughout the
      clinically relevant range of HIC with appropriate MRI acquisition techniques.

PMID- 15860671
TI  - Ectopic and IFN-induced expression of Fas overcomes resistance to Fas-mediated
      apoptosis in multiple myeloma cells.
AB  - Multiple myeloma (MM) is an as-yet incurable B-cell malignancy. Increased
      survival in vitro is a hallmark of MM cells, implying that a therapeutic
      potential may lie in circumventing antiapoptotic signals. We have previously
      reported that interferons (IFNs) sensitize MM cells to Fas/CD95-mediated
      apoptosis. In the present study, we explore the mechanism underlying this effect.
      In a wide screening of apoptosis-related genes, Apo2L/TRAIL (tumor necrosis
      factor [TNF]-related apoptosis inducing ligand) and Fas were identified as IFN
      targets. Sensitization to Fas-mediated apoptosis by IFNs was not affected by
      blocking Apo2L/TRAIL, suggesting that Apo2L/TRAIL is not a key mediator in this
      process. In contrast, we found that an elevated Fas expression was functionally
      linked to increased susceptibility to Fas-mediated apoptosis. This was further
      supported by the finding that IFN treatment enhanced Fas-mediated caspase-8
      activation, one of the earliest signaling events downstream receptor activation.
      In addition, IFN treatment attenuated the interleukin 6 (IL-6)-dependent
      activation of signal transducer and activator of transcription 3 (Stat3),
      interfering with a known survival pathway in MM that has previously been linked
      with resistance to Fas-mediated apoptosis. Taken together, our results show that
      IFN-induced up-regulation of Fas sensitizes MM cells to Fas-mediated apoptosis
      and suggest that attenuation of Stat3 activation may be a potentially important
      event in this process.

PMID- 15860672
TI  - Nurselike cells express BAFF and APRIL, which can promote survival of chronic
      lymphocytic leukemia cells via a paracrine pathway distinct from that of SDF
      1alpha.
AB  - We examined expression of B cell-activating factor of the tumor necrosis factor
      (TNF) family (BAFF) and a proliferation-inducing ligand (APRIL) on chronic
      lymphocytic leukemia (CLL) B cells and nurselike cells (NLCs), which
      differentiate from CD14+ cells when cultured with CLL B cells. NLCs expressed
      significantly higher levels of APRIL than monocytes and significantly higher
      levels of BAFF and APRIL than CLL B cells. Also, the viability of CLL B cells
      cultured with NLCs was significantly reduced when CLL B cells were cultured with
      decoy receptor of B-cell maturation antigen (BCMA), which can bind both BAFF and
      APRIL, but not with BAFF receptor:Fc (BAFF-R:Fc), which binds only to BAFF. The
      effect(s) of BAFF or APRIL on leukemia cell survival appeared additive and
      distinct from that of stromal cell-derived factor-1alpha (SDF-1alpha), which in
      contrast to BAFF or APRIL induced leukemia cell phosphorylation of p44/42 mitogen
      activated protein kinase (extracellular signal-regulated kinase-1/2 [ERK1/2]) and
      AKT. Conversely, BAFF and APRIL, but not SDF-1alpha, induced CLL-cell activation
      of the nuclear factor-kappaB1 (NF-kappaB1) and enhanced CLL-cell expression of
      the antiapoptotic protein Mcl-1. However, BAFF, but not APRIL, also induced CLL
      cell activation of NF-kappaB2. We conclude that BAFF and APRIL from NLCs can
      function in a paracrine manner to support leukemia cell survival via mechanisms
      that are distinct from those of SDF-1alpha, indicating that NLCs use multiple
      distinct pathways to support CLL-cell survival.

PMID- 15860673
TI  - Abductor tendons and muscles assessed at MR imaging after total hip arthroplasty
      in asymptomatic and symptomatic patients.
AB  - PURPOSE: To prospectively evaluate magnetic resonance (MR) imaging findings of
      abductor tendons and muscles in asymptomatic and symptomatic patients after
      lateral transgluteal total hip arthroplasty (THA). MATERIALS AND METHODS: The
      institutional review board approved the study, and all patients provided informed
      consent. Two musculoskeletal radiologists blinded to clinical information
      analyzed triplanar MR images of the greater trochanter obtained in 25 patients
      without and 39 patients with trochanteric pain and abductor weakness after THA.
      Tendon defects, diameter, signal intensity, and ossification; fatty atrophy; and
      bursal fluid collections were assessed. In 14 symptomatic patients, MR imaging
      and surgical findings were correlated. Differences in the frequencies of findings
      between the two groups were tested for significance by using chi2 analysis.
      RESULTS: Tendon defects were uncommon in asymptomatic patients and significantly
      more frequent in symptomatic patients: Two asymptomatic versus 22 symptomatic
      patients had gluteus minimus defects (P < .001); four asymptomatic versus 24
      symptomatic patients, lateral gluteus medius defects (P < .001); and no
      asymptomatic versus seven symptomatic patients, posterior gluteus medius defects
      (P = .025). In both patient groups, tendon signal intensity changes were
      frequent, with the exception of those in the posterior gluteus medius tendon,
      which demonstrated these changes more frequently in symptomatic patients (in 23
      vs five asymptomatic patients, P = .002). Tendon diameter changes were frequent
      in both groups but significantly (P = .001 to P = .009) more frequent in
      symptomatic patients (all tendon parts). Fatty atrophy was evident in the
      anterior two-thirds of the gluteus minimus muscle in both groups, without
      significant differences. In the posterosuperior third of the gluteus minimus
      muscle, however, differences in fatty atrophy between the two groups were
      significant (P = .026). Fatty atrophy of the gluteus medius muscle was present in
      symptomatic patients only, with significant differences among all muscle parts.
      Bursal fluid collections were more frequent in symptomatic patients (n = 24) than
      in asymptomatic patients (n = 8, P = .021). The MR imaging-based diagnosis was
      confirmed in all 14 patients who underwent revision surgery. CONCLUSION: Abductor
      tendon defects and fatty atrophy of the gluteus medius muscle and the posterior
      part of the gluteus minimus muscle are uncommon in asymptomatic patients after
      THA.

PMID- 15860674
TI  - Intermittent claudication: functional capacity and quality of life after exercise
      training or percutaneous transluminal angioplasty--systematic review.
AB  - PURPOSE: To systematically review published data about the short- and long-term
      effects of exercise training and angioplasty on functional capacity and quality
      of life of patients with intermittent claudication. MATERIALS AND METHODS:
      Articles published between January 1980 and February 2003 were included if
      patients had intermittent claudication treated with exercise training or
      angioplasty and if both functional capacity and quality-of-life scores from
      Medical Outcomes Study 36-Item Short Form health survey were reported for at
      least 3 months of follow-up. Data were pooled by using a random effects model and
      weighted means. Pooled results were compared between the treatment groups by
      using the chi2 test and the Student t test (alpha = .05, two sided). RESULTS: In
      the analyses, five studies (202 patients) were included in the exercise group,
      and three studies (470 patients), in the angioplasty group. At 3 months of follow
      up, the ankle-brachial index was significantly improved in the angioplasty group
      (mean change, 0.18; P < .01) but not in the exercise group (mean change, 0.01; P
      = .29). At 3 months, quality of life was significantly improved with regard to
      ratings of physical functioning and bodily pain in the exercise group (mean
      change, 18 and 10, respectively; P < .01) and physical role functioning in the
      angioplasty group (mean change, 30; P = .03). Mean change in ankle-brachial index
      significantly differed between the two treatment groups at 3 and 6 months (P <
      .01); mean change in quality-of-life scores did not. CONCLUSION: Improvement in
      quality of life was demonstrated after both exercise training and angioplasty,
      whereas functional capacity showed significant improvement after angioplasty. The
      ankle-brachial index significantly differed between the two treatment groups at 3
      and 6 months, whereas the quality-of-life scores did not.

PMID- 15860675
TI  - CT sign of brain swelling without concomitant parenchymal hypoattenuation:
      comparison with diffusion- and perfusion-weighted MR imaging.
AB  - PURPOSE: To retrospectively evaluate the apparent diffusion coefficient (ADC) on
      magnetic resonance (MR) images and the perfusion parameters of lesions that show
      brain swelling without concomitant parenchymal hypoattenuation on computed
      tomographic (CT) scans. MATERIALS AND METHODS: Review board approval was
      obtained, and informed consent was waived. A total of 14 patients (seven men and
      seven women; mean age, 64 years +/- 11) were retrospectively selected from the
      consecutive 172 patients with acute cerebral ischemia who underwent CT within 6
      hours of symptom onset. All patients had brain swelling without parenchymal
      hypoattenuation, including loss of gray-white matter distinction on CT scans, and
      they underwent diffusion- and perfusion-weighted MR imaging shortly after CT. CT
      attenuation, ADC, and perfusion parameters of relative cerebral blood volume
      (CBV), time to peak (TTP), and relative cerebral blood flow (CBF) were calculated
      for gray and white matter of the lesion. The measured values were compared with
      those of the contralateral hemisphere by using the paired t test; comparison of
      values of perfusion parameters among three subgroups was performed with the
      Kruskal-Wallis test. Arterial occlusions were determined with MR angiography or
      conventional angiography. RESULTS: The mean interval between initial CT and MR
      imaging was 2.4 hours +/- 0.9 (range, 0.4-3.4 hours). The ADC of lesions was
      similar to that of contralateral normal tissue (mean ADC ratio for gray matter
      and white matter, 0.99 and 0.97, respectively) (P > .05). Lesions had an
      increased relative CBV (P < .001), a mild to moderate TTP delay (P < .001), and a
      variable but not statistically significant reduction of relative CBF. The mean
      relative CBF of gray matter was less in patients who had complete infarction
      (0.81 +/- 0.16) than that in patients with partial infarction (0.99 +/- 0.16) or
      those with a normal radiologic outcome (1.12 +/- 0.22), but this difference was
      not statistically significant (P > .05). Proximal cerebral artery occlusions were
      found in all patients. In five (36%) patients, the lesion did not progress to
      infarction at follow-up. CONCLUSION: The CT sign of brain swelling without
      concomitant parenchymal hypoattenuation in patients with acute cerebral ischemia
      does not represent severe ischemic damage and may suggest ischemic penumbral or
      oligemic tissue.

PMID- 15860676
TI  - Anterior tibial tendon abnormalities: MR imaging findings.
AB  - PURPOSE: To retrospectively evaluate the magnetic resonance (MR) imaging findings
      of anterior tibial tendon (ATT) abnormalities. MATERIALS AND METHODS:
      Institutional review board approval was not necessary for review of patient
      images and was granted for examination of the volunteers; informed consent was
      obtained. MR imaging findings in 28 consecutive patients (20 women, eight men;
      mean age, 63.2 years) clinically suspected of having an ATT abnormality were
      compared with those in an age- and sex-matched control group of 28 asymptomatic
      volunteers (20 women, eight men; mean age, 62.9 years). Surgical correlation was
      available for 11 patients. The short-axis diameter of the ATT and the
      longitudinal extent of signal intensity abnormalities were measured (Mann-Whitney
      U test). Signal intensity abnormalities of the ATT and irregularities of the
      underlying tarsal bones were analyzed in consensus by two blinded radiologists
      (chi2 test). RESULTS: In the symptomatic group, three cases of tendinosis and 13
      partial and 12 complete ATT tears were diagnosed. In 11 cases (one case of
      tendinosis and two cases of partial and eight cases of complete ATT tear),
      surgical correlation was available and the MR imaging diagnosis was confirmed. In
      the asymptomatic group, four cases of tendinosis of the ATT were seen. The ATT
      diameter was significantly thicker in symptomatic patients at 1 cm (5.1 vs 3.1 mm
      in control group, P < .001), 3 cm (5.8 vs 3.4 mm, P < .001), and 6 cm (5.4 vs 4.3
      mm, P = .006) proximal to the distal point of insertion. Most ATT abnormalities
      (in 23 [82%] of 28 patients) were located within the first 3 cm proximal to the
      insertion. Signal intensity abnormalities were seen in the anterior portion of
      the ATT in two (7%) of the 28 symptomatic patients and in the posterior portion
      in 11 (39%); diffuse involvement was seen in 15 (54%). Bone spurs on the
      navicular surface (nine [32%] patients vs no [0%] control subjects, P = .001), a
      ridged shape of the medial surface of the medial cuneiform bone (13 [46%] vs one
      [4%], P < .001), and osteophyte formation at the first tarsometasarsal joint
      (eight [29%] vs two [7%], P = .036) were significantly more common in the
      symptomatic patient group. CONCLUSION: Characteristic findings of ATT
      abnormalities include tendon thickening (> or =5 mm) and diffuse or posterior
      signal intensity abnormalities of the tendon within 3 cm from the distal point of
      insertion.

PMID- 15860677
TI  - Bile leakage during transjugular intrahepatic portosystemic shunt creation: in
      vitro effect of bile on growth and function of human umbilical vein endothelium.
AB  - PURPOSE: To evaluate the effect of bile on growth and proliferation of human
      umbilical vein endothelium cultured in vitro, with a view toward clarifying the
      effect of bile leakage during transjugular intrahepatic portosystemic shunt
      creation. MATERIALS AND METHODS: This study was approved by the ethical review
      committee, and written informed consent was obtained from all mothers.
      Endothelial cells (ECs) were collected from human umbilical veins and cultured in
      vitro. After 24-48 hours in culture, ECs were distributed into groups
      supplemented with the following concentrations of bile in the culture medium: 0%,
      5.0%, 10.0%, 15.0%, 20.0%, and 25.0%. The cells were harvested 5 days after
      supplementation with bile. The morphologic features, von Willebrand factor (vWF)
      level, tetrazolium salt (MTT) assay value of light absorption, total protein
      level, and nitric oxide synthase (NOS) activity of the ECs were evaluated.
      RESULTS: All explanted cells were identified as ECs by using the vWF test.
      Compared with ECs in the control group without bile, ECs in culture medium with a
      bile concentration of 5.0%, 10.0%, or 15.0% showed no marked morphologic changes,
      whereas ECs in culture medium with a bile concentration of 20.0% or 25.0% were
      reduced greatly in number and looked markedly immature. The MTT value of light
      absorption, total protein level, and vWF secretion were significantly decreased
      (P < .05 for all) in ECs in culture medium with 25.0% bile compared with these
      parameters in ECs in culture medium without bile, although these parameters did
      not significantly differ between the ECs in culture medium of 5.0% or 10.0% bile
      and the ECs in culture medium without bile. Compared with NOS activity in ECs
      when no bile was present in the culture medium, NOS activity in ECs was
      significantly decreased at all bile concentrations (P < .05). CONCLUSION: Low
      concentrations of bile do not markedly inhibit cell growth; the inhibiting effect
      of bile on ECs progresses with an increase in bile concentration.

PMID- 15860678
TI  - Cerebral MR venography in children: comparison of 2D time-of-flight and
      gadolinium-enhanced 3D gradient-echo techniques.
AB  - PURPOSE: To prospectively compare two-dimensional (2D) time-of-flight cerebral
      magnetic resonance (MR) venography with gadolinium-enhanced three-dimensional
      (3D) gradient-echo cerebral MR venography in children. MATERIALS AND METHODS:
      This investigation had investigational review board approval and was Health
      Insurance Portability and Accountability Act compliant; parental informed consent
      was obtained. Thirty-seven patients (20 boys, 17 girls) who ranged in age from 4
      days to 15 years underwent 2D and 3D MR venography. Two pediatric
      neuroradiologists compared the visibility of the superior sagittal, straight,
      transverse, and sigmoid sinuses and the internal jugular veins on images obtained
      with the two sequences. RESULTS: In 17 (46%) of the 37 patients, the sequences
      were equivalent in terms of their depiction of venous anatomy. In 19 (51%) of the
      37 patients, 3D MR venography was superior to 2D MR venography. Suboptimal
      enhancement of veins occurred in one (3%) patient at 3D MR venography. Venous
      anomalies suggested at 2D MR venography but not present at 3D MR venography
      included flow gaps in the nondominant transverse sinuses of four patients,
      unilateral transverse sinus atresia in eight, and a narrowed superior sagittal
      sinus in two. Two-dimensional MR venography results failed to reveal a persistent
      falcine sinus associated with straight sinus atresia in one patient and suggested
      transverse sinus thrombosis in two patients in whom 3D MR venography results were
      normal. Additionally, the extent of dural thrombosis was overestimated at 2D MR
      venography in one patient. As compared with 3D MR venography, 2D MR venography
      failed to reveal sigmoid sinus stenosis in one patient and poorly depicted
      posterior fossa dural sinus anatomy in two patients with dural arteriovenous
      fistula. CONCLUSION: Three-dimensional MR venography is often superior to 2D MR
      venography in the delineation of major cerebral venous structures in children.
      Most of the artifactual loss of vascular signal seen with the use of 2D MR
      venography occurred in nondominant transverse sinuses.

PMID- 15860679
TI  - Muscle sarcoplasmic reticulum Ca2+ cycling adaptations during 16 h of heavy
      intermittent cycle exercise.
AB  - The repetition-dependent effects of a repetitive heavy exercise protocol
      previously shown to alter muscle mechanic behavior (Green HJ, Duhamel TA, Ferth
      S, Holloway GP, Thomas MM, Tupling AR, Rich SM, and Yau JE. J Appl Physiol 97:
      2166-2175, 2004) on muscle sarcoplasmic reticulum (SR) Ca2+-transport properties,
      measured in vitro, were examined in 12 untrained volunteers [peak aerobic power
      (VO2(peak)) = 44.3 +/- 0.66 ml x kg(-1) x min(-1)]. The protocol involved 6 min
      of cycle exercise performed at approximately 91% VO2(peak) once per hour for 16
      h. Tissue samples were obtained from the vastus lateralis before (B) and after
      (A) exercise at repetitions 1 (R1), 2 (R2), 9 (R9), and 16 (R16). Reductions (P <
      0.05) in maximal Ca2+-ATPase activity (Vmax) of 26 and 12% with exercise were
      only observed at R1 and R16, respectively. Vmax remained depressed (P < 0.05) at
      R2 (B) but not at R9 (B) and R16 (B). No changes were observed in two other
      kinetic properties of the enzyme, namely the Hill coefficient (defined as the
      slope of the relationship between Ca2+-ATPase activity and free Ca2+
      concentration) and the Ca50 (defined as the free Ca2+ concentration needed to
      elicit 50% Vmax). Changes in Ca2+ uptake (measured at 2,000 nM) with exercise and
      recovery generally paralleled Vmax. The apparent coupling ratio, defined as the
      ratio between Ca2+ uptake and Vmax, was unaffected by the intermittent protocol.
      Reductions (P < 0.05) in phase 1 Ca2+ release (32%) were only observed at R1. No
      differences were observed between B and A for R2, R9, and R16 or between B and B
      for R1, R2, R9, and R16. The changes in phase 2 Ca2+ release were as observed for
      phase 1 Ca2+ release. It is concluded that the SR Ca2+-handling properties, in
      general, display rapid adaptations to repetitive exercise.

PMID- 15860680
TI  - Muscle performance during maximal isometric and dynamic contractions is
      influenced by the stiffness of the tendinous structures.
AB  - Contractile force is transmitted to the skeleton through tendons and aponeuroses,
      and, although it is appreciated that the mechanocharacteristics of these tissues
      play an important role for movement performance with respect to energy storage,
      the association between tendon mechanical properties and the contractile muscle
      output during high-force movement tasks remains elusive. The purpose of the study
      was to investigate the relation between the mechanical properties of the
      connective tissue and muscle performance in maximal isometric and dynamic muscle
      actions. Sixteen trained men participated in the study. The mechanical properties
      of the vastus lateralis tendon-aponeurosis complex were assessed by
      ultrasonography. Maximal isometric knee extensor force and rate of torque
      development (RTD) were determined. Dynamic performance was assessed by maximal
      squat jumps and countermovement jumps on a force plate. From the vertical ground
      reaction force, maximal jump height, jump power, and force-/velocity-related
      determinants of jump performance were obtained. RTD was positively related to the
      stiffness of the tendinous structures (r = 0.55, P < 0.05), indicating that
      tendon mechanical properties may account for up to 30% of the variance in RTD. A
      correlation was observed between stiffness and maximal jump height in squat jumps
      and countermovement jumps (r = 0.64, P < 0.05 and r = 0.55, P < 0.05). Power,
      force, and velocity parameters obtained during the jumps were significantly
      correlated to tendon stiffness. These data indicate that muscle output in high
      force isometric and dynamic muscle actions is positively related to the stiffness
      of the tendinous structures, possibly by means of a more effective force
      transmission from the contractile elements to the bone.

PMID- 15860681
TI  - AICAR and hyperosmotic stress increase insulin-stimulated glucose transport.
AB  - Sensitivity of glucose transport to stimulation by insulin has been shown to
      occur concomitant with activation of the AMP-activated protein kinase (AMPK) in
      skeletal muscle, suggesting a role of AMPK in regulation of insulin action. The
      purpose of the present study was to evaluate a possible role of AMPK in
      potentiation of insulin action in muscle cells. The experimental model involved
      insulin-responsive C2C12 myotubes that exhibit a twofold increase in glucose
      transport in the presence of insulin. Treatment of myotubes with the AMPK
      activator 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR),
      followed by a 2-h recovery, augmented the ability of insulin to stimulate glucose
      transport. Similarly, incubation in hyperosmotic medium, another AMPK-activating
      treatment, acted synergistically with insulin to stimulate glucose transport.
      Furthermore, the increase in insulin action caused by hyperosmotic stress was
      prevented by inclusion of compound C, an AMPK inhibitor, in hyperosmotic medium.
      In addition, iodotubercidin, a general kinase inhibitor that is effective against
      AMPK, also prevented the combined effects of insulin and hyperosmotic stress on
      glucose transport. The new information provided by these data is that previously
      reported AICAR effects on insulin action are generalizable to myotubes,
      hyperosmotic stress and insulin synergistically increase glucose transport, and
      AMPK appears to mediate potentiation of insulin action.

PMID- 15860682
TI  - Role of arterial hypoxemia and pulmonary mechanics in exercise limitation in
      adults with cystic fibrosis.
AB  - We tested the hypothesis that maximal exercise performance in adults with cystic
      fibrosis is limited by arterial hypoxemia. In study 1, patients completed two
      maximal exercise tests, a control and a test with 400 ml of added dead space.
      Maximal O2 consumption was significantly lower in the added dead space study vs.
      control (1.04 +/- 0.15 vs. 1.20 +/- 0.11 l/min; P < 0.05), with no difference in
      peak ventilation. There was significant O2 desaturation during exercise that was
      equal in both control and added dead space studies. The decrease in maximal O2
      consumption with added dead space suggests that maximal exercise in cystic
      fibrosis is limited by respiratory factors. We subsequently examined whether
      pulmonary mechanics or arterial hypoxemia limits maximal exercise performance. In
      study 2, patients completed two maximal exercise tests, a control and a test with
      400 ml of added dead space while also breathing 38% O2. Added dead space was used
      to overcome the suppressive effects of hyperoxia on minute ventilation. Maximal
      O2 consumption was significantly higher with added dead space and 38% O2 vs.
      control (1.62 +/- 0.16 vs. 1.43 +/- 0.14 l/min; P < 0.05). Peak ventilation and
      O2 saturation were significantly greater in the added dead space and 38% O2 test
      vs. control. The increase in maximal O2 consumption and peak ventilation with
      added dead space and 38% O2 suggests that maximal exercise in cystic fibrosis is
      limited by arterial hypoxemia.

PMID- 15860683
TI  - Uncertainty of knee joint muscle activity during knee joint torque exertion: the
      significance of controlling adjacent joint torque.
AB  - In the single-joint torque exertion task, which has been widely used to control
      muscle activity, only the relevant joint torque is specified. However, the
      neglect of the neighboring joint could make the procedure unreliable, considering
      our previous result that even monoarticular muscle activity level is indefinite
      without specifying the adjacent joint torque. Here we examined the amount of hip
      joint torque generated with knee joint torque and its influence on the activity
      of the knee joint muscles. Twelve healthy subjects were requested to exert
      various levels of isometric knee joint torque. The knee and hip joint torques
      were obtained by using a custom-made device. Because no information about hip
      joint torque was provided to the subjects, the hip joint torque measured here was
      a secondary one associated with the task. The amount of hip joint torque varied
      among subjects, indicating that they adopted various strategies to achieve the
      task. In some subjects, there was a considerable internal variability in the hip
      joint torque. Such variability was not negligible, because the knee joint muscle
      activity level with respect to the knee joint torque, as quantified by surface
      electromyography (EMG), changed significantly when the subjects were requested to
      change the strategy. This change occurred in a very systematic manner: in the
      case of the knee extension, as the hip flexion torque was larger, the activity of
      mono- and biarticular knee extensors decreased and increased, respectively. These
      results indicate that the conventional single knee joint torque exertion has the
      drawback that the intersubject and/or intertrial variability is inevitable in the
      relative contribution among mono- and biarticular muscles because of the
      uncertainty of the hip joint torque. We discuss that the viewpoint that both
      joint torques need to be considered will bring insights into various
      controversial problems such as the shape of the EMG-force relationship, neural
      factors that help determine the effect of muscle strength training, and so on.

PMID- 15860684
TI  - Glycogenin activity and mRNA expression in response to volitional exhaustion in
      human skeletal muscle.
AB  - Glycogenolysis results in the selective catabolism of individual glycogen
      granules by glycogen phosphorylase. However, once the carbohydrate portion of the
      granule is metabolized, the fate of glycogenin, the protein primer of granule
      formation, is not known. To examine this, male subjects (n = 6) exercised to
      volitional exhaustion (Exh) on a cycle ergometer at 75% maximal O2 uptake. Muscle
      biopsies were obtained at rest, 30 min, and Exh (99 +/- 10 min). At rest, total
      glycogen concentration was 497 +/- 41 and declined to 378 +/- 51 mmol glucosyl
      units/kg dry wt following 30 min of exercise (P < 0.05). There were no
      significant changes in proglycogen, macroglycogen, glycogenin activity, or mRNA
      in this period (P > or = 0.05). Exh resulted in decreases in total glycogen,
      proglycogen, and macroglycogen as well as glycogenin activity (P < 0.05). These
      decrements were associated with a 1.9 +/- 0.4-fold increase in glycogenin mRNA
      over resting values (P < 0.05). Glycogenolysis in the initial exercise period (0
      30 min) was not adequate to induce changes in glycogenin; however, later in
      exercise when concentration and granule number decreased further, decrements in
      glycogenin activity and increases in glycogenin mRNA were demonstrated. Results
      show that glycogenin becomes inactivated with glycogen catabolism and that this
      event coincides with an increase in glycogenin gene expression as exercise and
      glycogenolysis progress.

PMID- 15860685
TI  - Sex-based differences in skeletal muscle function and morphology with short-term
      limb immobilization.
AB  - The purpose of this study was to determine the effects of short-term (14-day)
      unilateral leg immobilization using a simple knee brace (60 degree flexion)- or
      crutch-mediated model on muscle function and morphology in men (M, n = 13) and
      women (W, n = 14). Isometric and isokinetic (concentric-slow, 0.52 rad/s and
      fast, 5.24 rad/s) knee extensor peak torque was determined at three time points
      (Pre, Day-2, and Day-14). At the same time points, magnetic resonance imaging was
      used to measure the cross-sectional area of the quadriceps femoris and dual
      energy X-ray absorptiometry scanning was used to calculate leg lean mass. Muscle
      biopsies were taken from vastus lateralis at Pre and Day-14 for myosin ATPase and
      myosin heavy chain analysis. Women showed greater decreases (Pre vs. Day-14)
      compared with men in specific strength (N/cm2) for isometric [M = 3.1 +/- 13.3, W
      = 17.1 +/- 15.9%; P = 0.055 (mean +/- SD)] and concentric-slow (M = 4.7 +/- 11.3,
      W = 16.6 +/- 18.4%; P < 0.05) contractions. There were no immobilization-induced
      sex-specific differences in the decrease in quadriceps femoris cross-sectional
      area (M = 5.7 +/- 5.0, W = 5.9 +/- 5.2%) or leg lean mass (M = 3.7 +/- 4.2, W =
      2.7 +/- 2.8%). There were no fiber-type transformations, and the decreases in
      type I (M = 4.8 +/- 5.0, W = 5.9 +/- 3.4%), IIa (M = 7.9 +/- 9.9, W = 8.8 +/-
      8.0%), and IIx (M = 10.7 +/- 10.8, W = 10.8 +/- 12.1%) fiber areas were similar
      between sexes. These findings indicate that immobilization-induced loss of knee
      extensor muscle strength is greater in women compared with men despite a similar
      extent of atrophy at the myofiber and whole muscle levels after 14 days of
      unilateral leg immobilization. Furthermore, we have described an effective and
      safe knee immobilization method that results in reductions in quadriceps muscle
      strength and size.

PMID- 15860686
TI  - Cerebral autoregulation is preserved in postural tachycardia syndrome.
AB  - To test whether cerebral autoregulation is impaired in patients with postural
      tachycardia syndrome (POTS), we evaluated 17 healthy control subjects and 27
      patients with POTS. Blood pressure, heart rate, and cerebral blood velocity
      (transcranial Doppler) were recorded at rest and during 80 degree head-up tilt
      (HUT). Static cerebral autoregulation, as assessed from the change in
      cerebrovascular resistance during HUT, was the same in POTS and in controls. The
      properties of dynamic cerebral autoregulation were inferred from transfer gain,
      coherence, and phase of the relationship between blood pressure and cerebral
      blood velocity estimated from filtered data segments (0.02-0.8 Hz). Dynamic
      cerebral autoregulation of patients with POTS did not differ from that of
      controls. The patients' dynamic cerebral autoregulation did not change over the
      course of HUT, despite increased tachycardia suggestive of worsening orthostatic
      stress. Inflation of military anti-shock trouser pants substantially reduced the
      tachycardia of patients with POTS without affecting cerebral autoregulation.
      Symptoms of orthostatic intolerance were reduced in one-half of the patients
      following military anti-shock trouser pants inflation. We conclude that cerebral
      perfusion and autoregulation in many patients with POTS do not differ from that
      of normal control subjects.

PMID- 15860687
TI  - Blood pressure and blood flow variation during postural change from sitting to
      standing: model development and validation.
AB  - Short-term cardiovascular responses to postural change from sitting to standing
      involve complex interactions between the autonomic nervous system, which
      regulates blood pressure, and cerebral autoregulation, which maintains cerebral
      perfusion. We present a mathematical model that can predict dynamic changes in
      beat-to-beat arterial blood pressure and middle cerebral artery blood flow
      velocity during postural change from sitting to standing. Our cardiovascular
      model utilizes 11 compartments to describe blood pressure, blood flow,
      compliance, and resistance in the heart and systemic circulation. To include
      dynamics due to the pulsatile nature of blood pressure and blood flow,
      resistances in the large systemic arteries are modeled using nonlinear functions
      of pressure. A physiologically based submodel is used to describe effects of
      gravity on venous blood pooling during postural change. Two types of control
      mechanisms are included: 1) autonomic regulation mediated by sympathetic and
      parasympathetic responses, which affect heart rate, cardiac contractility,
      resistance, and compliance, and 2) autoregulation mediated by responses to local
      changes in myogenic tone, metabolic demand, and CO(2) concentration, which affect
      cerebrovascular resistance. Finally, we formulate an inverse least-squares
      problem to estimate parameters and demonstrate that our mathematical model is in
      agreement with physiological data from a young subject during postural change
      from sitting to standing.

PMID- 15860688
TI  - Corticotropin-releasing hormone effects on human pregnant vs. nonpregnant
      myometrium explants estimated from a mathematical model of uterine contraction.
AB  - In this paper, we applied a new theoretical model of uterine contraction to a
      large panel of human pregnant and nonpregnant myometrial strips, treated or not
      by corticotrophin-releasing hormone (CRH). This model is based on a fine analysis
      of the contraction curves. This analysis yielded four mathematical parameters
      (beta, theta, tau 1, and tau 2) related to excitability, duration of plateau
      phase, and time constants for relaxation describing, respectively, the different
      portions of the contraction cycle. This leads to specific differences in
      spontaneous contractile activity between pregnant and nonpregnant states. The
      relaxing effect of CRH in the pregnant state is presumably correlated with the
      origin of the strips (the lower uterine segment). Besides our observation of a
      specific receptor-dependent relaxing effect of CRH in both pregnant and
      nonpregnant myometrium, we could identify highly significant effects at given CRH
      concentration for beta in nonpregnant myometrium and for theta, tau 1, and tau 2
      in pregnant myometrium. In addition, highly significant differences were found
      between pregnant and nonpregnant myometrium. Also, we discovered a strong
      correlation between theta and tau 1, specifically in the pregnant state. Although
      the biochemical signification of these results remains to be elucidated, they
      contribute to emphasize the complex network of CRH action at the myometrial
      level. Furthermore, our approach could pave the way toward a better analysis of
      the efficacy of the uterine contractile behavior.

PMID- 15860689
TI  - Exercise without weight loss is an effective strategy for obesity reduction in
      obese individuals with and without Type 2 diabetes.
AB  - It is unclear whether chronic exercise without caloric restriction or weight loss
      is a useful strategy for obesity reduction in obese men with and without Type 2
      diabetes (T2D). We examined the effects of exercise without weight loss on total
      and regional adiposity and skeletal muscle mass and composition in lean men and
      in obese men with and without T2D. Twenty-four men participated in 13 wk of
      supervised aerobic exercise, five times per week for 60 min at a moderate
      intensity (approximately 60% peak oxygen uptake). Total and regional body
      composition was measured by magnetic resonance imaging. Skeletal muscle
      composition was determined using computed tomography. Cardiorespiratory fitness
      was assessed using a graded maximal treadmill test. Body weight did not change
      within any group in response to exercise (P > 0.1). Significant reductions in
      total, abdominal subcutaneous, and visceral fat were observed within each group
      (P < 0.01). The reduction in total and abdominal subcutaneous fat was not
      different (P > 0.1) between groups; however, the reduction in visceral fat was
      greater (P < 0.01) in the obese and T2D groups by comparison to the lean group. A
      significant (P < 0.01) increase in total skeletal muscle, high-density muscle
      area, and mean muscle attenuation was observed independent of group, and these
      changes were not different between groups (P > 0.1). Accordingly, whole body fat
      to-muscle ratio was increased (P < 0.01) independent of groups. In conclusion,
      regular exercise without weight loss is associated with a substantial reduction
      in total and visceral fat and in skeletal muscle lipid in both obesity and T2D.

PMID- 15860690
TI  - Ziprasidone pretreatment attenuates the lethal effects of cocaine in a mouse
      model.
AB  - BACKGROUND: Cocaine intoxication is a common cause of agitation in emergency
      department patients. Ziprasidone, an atypical antipsychotic, is being
      increasingly used for sedation of agitated patients in the emergency department.
      OBJECTIVES: To provide preliminary animal data on the efficacy of ziprasidone for
      the treatment of acute cocaine poisoning. METHODS: This was a randomized, blinded
      comparison of ziprasidone and placebo for the prevention of seizures and apparent
      lethality in a mouse model of cocaine intoxication. Animals were assigned to
      either placebo or 0.4 mg/kg or 1.2 mg/m(2) of ziprasidone intraperitoneally 30
      minutes prior to administration of 105 mg/kg of cocaine. Study outcomes were the
      proportions of animals having seizures and the apparent lethality. RESULTS: 1.2
      mg/m(2) of ziprasidone decreased the lethal effects of cocaine by 50%, while 0.4
      mg/kg decreased lethality by 13%. There was no effect on seizures at either dose.
      CONCLUSIONS: Ziprasidone pretreatment decreased lethality in this mouse model of
      severe cocaine intoxication.

PMID- 15860691
TI  - Adenosine A1 antagonism attenuates beta-adrenergic-resistant sudden hypoxic
      cardiac insufficiency.
AB  - OBJECTIVES: In states such as hypoxia, shock, and cardiac arrest, compromised
      systemic oxygenation or perfusion appears to induce cardiac insufficiency that
      can be resistant to beta-adrenergic drugs. Elevated levels of adenosine may
      mediate such beta-adrenergic-resistant cardiac insufficiency via the adenosine
      A(1) receptor (A(1)AdoR). The objective of this study was to test the hypothesis
      that selective A(1)AdoR antagonism attenuates hypoxic cardiac insufficiency more
      efficaciously than beta(1)-adrenergic agonism or nonselective adenosine
      antagonism. METHODS: Rats were paralyzed and ventilated to a pCO(2) level of 35
      40 mm Hg. Ten minutes before hypoxia (inspired o(2) concentration = 5%), rats
      were treated intravenously with one of the following: 0.1 mg/kg BG-9719 (n = 9),
      10 mg/kg NPC-205 (n = 10; BG-9719 and NPC-205 are selective A(1)AdoR antagonists,
      with durations of action of 30-60 minutes and 60-90 minutes, respectively), 10
      mg/kg aminophylline (n = 12), 5 microg/kg/min dobutamine (n = 11), or control
      solutions. These drug doses maximized survival duration in dose-response studies.
      RESULTS: Before hypoxia, cardiac work was increased more by aminophylline and
      dobutamine than by BG-9719. Mean (+/-SEM) duration of survival (in minutes) after
      hypoxia increased from <13 (control solutions) to 13.8 (+/-1.4) (dobutamine),
      20.0 (+/-1.6) (aminophylline), 31.7 (+/-4.6) (BG-9719), and 40.5 (+/-7.5) (NPC
      205) (p < 0.0001). Heart rate and dP/dt decreased rapidly after hypoxia, but
      decreases were attenuated with BG-9719 and NPC-205 compared with dobutamine (p <
      0.05) and tended toward attenuation with aminophylline. CONCLUSIONS: BG-9719 and
      NPC-205 improved survival duration, heart rate, and left ventricular
      contractility during hypoxia more efficaciously than dobutamine and possibly
      aminophylline. Selective A(1)AdoR antagonists warrant further study as
      alternatives to beta-adrenergic agonists in hypoxia, shock, and cardiac arrest,
      in which compromised systemic perfusion or oxygenation impairs cardiac output.

PMID- 15860692
TI  - Out-of-hospital administration of albuterol for asthma by basic life support
      providers.
AB  - BACKGROUND: Each year, approximately 40,000 patients with acute asthma are
      transported by the Fire Department of New York City (NYC) Emergency Medical
      Services (EMS). Out-of-hospital administration of bronchodilator therapy has,
      however, been restricted by scope of practice to advanced life support (ALS)
      providers. Since the rapid availability of ALS units cannot always be assured,
      some individuals with acute asthma may receive only basic life support (BLS)
      measures in the field. OBJECTIVES: To demonstrate that basic emergency medical
      technicians (EMT-Bs) are able to effectively administer nebulized albuterol to
      asthma patients in the out-of-hospital environment. METHODS: This was a
      prospective, observational cohort study of 9-1-1 asthma calls received by the NYC
      EMS system for patients between the ages of 1 and 65 years. Baseline peak
      expiratory flow rate (PEFR) and other clinical measures were obtained prior to
      and following BLS administration of one or two treatments with nebulized
      albuterol. RESULTS: Data were available for 3,351 patients over a one-year study
      period. One out-of-hospital albuterol treatment was given in 60%, while 40% of
      the patients received two. The PEFRs increased from 40.4% predicted (SD +/-21.0)
      to 54.8% predicted (SD +/-26.1), for a posttreatment improvement of 14.4% points
      (95% CI = 13.8 to 15.1). Other clinical outcome measures, including dyspnea
      index, respiratory rate, and use of accessory muscles, also showed improvement.
      CONCLUSIONS: This study demonstrates that EMT-Bs can effectively administer
      albuterol to acute asthma patients in the out-of-hospital environment.

PMID- 15860693
TI  - A multiphase disaster training exercise for emergency medicine residents:
      opportunity knocks.
AB  - BACKGROUND: Disaster planning is a core curriculum requirement for emergency
      medicine (EM) residency programs. Few comprehensive training opportunities in
      disaster planning incorporating the appropriate competencies have been reported.
      OBJECTIVES: To design, pilot, and evaluate a combination interactive Web-based
      disaster planning curriculum and real-time multidisciplinary full-scale disaster
      exercise. METHODS: Residents were assigned to groups led by a faculty mentor.
      Each group used an Internet-based platform to review the literature pertaining to
      their component of a disaster plan. The groups then used the platform to redesign
      an existing institutional disaster plan. Finally, they implemented their disaster
      plan for 80 simulated casualties resulting from a police, fire department, and
      emergency medical services multiple-casualty rescue exercise. All health
      professions then participated in a joint debriefing session. All aspects of the
      program were supervised by specialty EM faculty, and the exercise was evaluated
      using a five-point Likert scale with specific anchored descriptors. RESULTS:
      Sixteen residents and 17 faculty members participated in the exercise. Trained
      volunteers and high-fidelity simulations represented casualties varying in age
      from 6 months to 65 years, and in severity from ambulatory to moribund. Residents
      found the exercise enjoyable (4.9/5), relevant (4.6/5), and educational (4.8/5).
      CONCLUSIONS: Emergency medicine residency programs can benefit from participating
      in high-quality medical disaster exercises coordinated with local disaster
      response agencies. Residents report high satisfaction and learning from realistic
      simulations of disasters, and from collaboration with other community services.

PMID- 15860694
TI  - Academic career development for emergency medicine residents: a road map.
AB  - As the marketplace for academic positions in emergency medicine grows more
      competitive, it becomes increasingly important for residents who desire academic
      careers to distinguish themselves during their residency. This report attempts to
      outline a road map for department and residency program leaders to help their
      houseofficers become successful candidates for an academic emergency medicine
      position. Specific ways a resident can enhance his or her "academic
      marketability" include 1) involvement in research, 2) establishment of a track
      record of productivity via scholarly writing, 3) awareness of the literature in
      the specialty, 4) involvement in specialty organizations and hospital committees,
      5) competition for national awards, 6) gaining education skills, 7) developing an
      academic niche, and 8) fellowship training.

PMID- 15860695
TI  - An evaluation of out-of-hospital advanced airway management in an urban setting.
AB  - OBJECTIVES: To determine the success and complication rates associated with
      endotracheal intubation in an urban emergency medical services (EMS) system.
      METHODS: This study evaluated consecutive airway interventions between March 2001
      and May 2001 performed by paramedics from the Denver Health Paramedic Division in
      Denver, Colorado. Patients were identified and enrolled prospectively with the
      identification of all patients for whom intubation was attempted. A retrospective
      chart review of the emergency department (ED), intensive care unit, other
      hospital records, and the coroner's records was then conducted with the intent of
      identifying all complications related to attempted intubation, including the
      placement of each endotracheal tube. RESULTS: A total of 278 patients were
      included in this study. Of these, 154 (55%) had an initial nasal intubation
      attempt, and 124 (45%) had an initial oral intubation attempt. Of the 278
      patients for whom an intubation was attempted, 234 (84%, 95% CI = 77% to 88%)
      were reported by paramedics to be successfully intubated. Of 114 nasal
      intubations reported as successful by paramedics, two (2%; 95% CI = 0.2% to 6%)
      were found to be misplaced. Of the 120 oral intubations reported as successful by
      paramedics, one (1%; 95% CI = 0.02% to 5%) was found to be misplaced. Of the 278
      patients, 22 (8%; 95% CI = 5% to 12%) had complications; three (1%; 95% CI = 0.2%
      to 3%) endotracheal tubes were incorrectly positioned, two (0.7%; 95% CI = 0.08%
      to 3%) of which were undetected esophageal intubations and one (0.4%; 95% CI = 0
      to 2%) of which was in the posterior pharynx. CONCLUSIONS: Reasonable success and
      complication rates of endotracheal intubation in the out-of-hospital setting can
      be achieved in a busy, urban EMS system without the assistance of medications.

PMID- 15860696
TI  - Observational study of intravenous versus oral corticosteroids for acute asthma:
      an example of confounding by severity.
AB  - OBJECTIVES: To demonstrate the problem of "confounding by severity" using the
      example of intravenous (IV) versus oral corticosteroids for the treatment of
      acute asthma. Double-blind, randomized trials have clearly demonstrated that IV
      and oral corticosteroids have comparable efficacy. METHODS: Using a standardized
      protocol, 64 emergency departments enrolled 1,847 patients, aged 18-54 years,
      with acute asthma. Because route of corticosteroid therapy was not randomized,
      potential confounders of the association between corticosteroid route and
      hospital admission were controlled for by multivariate logistic regression and
      stratification. RESULTS: Among the 1,193 patients, 383 (32%) received IV
      corticosteroids and 810 (68%) received oral corticosteroids. The two groups
      differed markedly at baseline, with patients receiving IV corticosteroids having
      more severe asthma. Overall, patients receiving IV corticosteroids were more
      likely to be admitted or experience a relapse event within 48 hours (51% vs. 19%;
      p < 0.001). On multivariate analysis, patients receiving IV corticosteroids
      remained more likely to be admitted or experience a relapse event within 48 hours
      (odds ratio = 2.6; 95% confidence interval = 1.2 to 6.0). CONCLUSIONS: In this
      observational study, patients with worse asthma exacerbations were more likely to
      receive IV corticosteroids as compared with oral corticosteroids. Although we
      controlled for many markers of asthma severity, we were unable to completely
      control for baseline differences between the IV and oral corticosteroid groups.
      Observational research continues to serve as an important tool for describing
      problems and for understanding many exposure-disease associations. For examining
      the impact of treatments on adverse outcomes, randomized trials are often
      required to avoid intractable confounding by severity.

PMID- 15860697
TI  - Disagreement between formal and medical record criteria for the diagnosis of
      acute coronary syndrome.
AB  - OBJECTIVES: To measure agreement between formal and medical record criteria for
      the diagnosis of acute coronary syndrome (ACS) among patients undergoing an
      emergency department evaluation for potential acute coronary symptoms. METHODS:
      Cases of ACS were determined by both formal (World Health Organization 1984
      criteria for acute myocardial infarction [AMI], Braunwald criteria for unstable
      angina pectoris [UAP]) and medical record criteria. In the latter, a diagnosis
      was made if providers indicated AMI or UAP anywhere in the medical record. All
      information included in formal criteria was available to clinicians establishing
      the medical record diagnosis. The two criteria for diagnosis were compared, and a
      kappa value was recorded. Two blinded observers adjudicated discordant cases,
      with a kappa value recorded. Disagreements between these two coinvestigators were
      resolved by a Delphi technique. RESULTS: A total of 375 eligible subjects were
      enrolled, of whom 65 (17%; 45 AMI, 20 UAP) had ACS by both sets of criteria.
      Formal and medical record criteria disagreed in 32 subjects. This represented 9%
      (95% confidence interval = 6% to 12%) of the overall study population but 33%
      (95% confidence interval = 23% to 43%) of subjects with possible ACS.
      Coinvestigators acting as judges and blinded to each other's determinations
      agreed that 25 of these subjects had ACS and three did not; they disagreed on
      four subjects (kappa = 0.54). Among these four subjects, a Delphi consensus
      technique determined that two subjects had AMI and two had no ACS. CONCLUSIONS:
      In a single-site study, among subjects who have possible ACS as determined by
      either or both formal and medical record criteria, these two sets of criteria
      disagree in almost one third of cases. Among discordant cases, even two expert
      judges frequently disagreed on the final diagnosis. A modified Delphi technique
      to address these disagreements is described.

PMID- 15860698
TI  - Clinicopathological conference: a 42-year-old woman with respiratory distress,
      abdominal pain, and hypertension.

PMID- 15860699
TI  - Are we ignoring the evidence?

PMID- 15860700
TI  - Family presence during invasive medical procedures: the struggle for an option.

PMID- 15860701
TI  - Topical nonsteroidal anti-inflammatory drugs for corneal abrasions: meta-analysis
      of randomized trials.
AB  - OBJECTIVES: To determine the effectiveness of topical nonsteroidal anti
      inflammatory drugs (NSAIDs) in traumatic corneal abrasions. METHODS: This was a
      systematic literature review and meta-analysis of randomized clinical trials
      (RCTs). The following databases were searched: MEDLINE (1966-2004), EMBASE (1980
      2004), and Cochrane Central Register of Controlled Trials and Database of
      Systematic Reviews (first quarter 2004). The structured search strategy included
      a RCT filter and the terms "cornea," "wounds and injuries," "trauma," "corneal
      diseases," "eye injuries," "anti-inflammatory agents, nonsteroidal" and specific
      trade names of topical NSAIDs. In addition, four journals in ophthalmology and
      emergency medicine were hand searched. Two authors independently reviewed
      citations from the literature searches. To be included, studies had to be RCTs
      evaluating topical NSAIDs in traumatic corneal abrasions. Trials were included
      regardless of language or whether they were unpublished or published. Exclusion
      criteria were corneal ulcers, nonrandomized studies, animal studies, or
      perioperative setting. Outcomes were pain scale scores at 24 hours and adverse
      effects. Two independent reviewers assessed four trial quality components:
      randomization, double blinding, reporting of withdrawals, and concealment of
      allocation. Weighted mean difference, using a random effects model, was
      calculated. RESULTS: Of the 200 citations identified, 11 RCTs met inclusion
      criteria. Eight trials were identified from the MEDLINE search, two from the
      EMBASE search, and one from conference proceedings. Seven trials enrolled fewer
      than 100 patients, and more than half of the studies were conducted in Europe.
      Five trials reported suitable data for analysis. The overall weighted mean
      difference for 459 patients was a reduction in pain by 1.30 points (95%
      confidence interval = -1.56 to -1.03) on the pain scale. Five of the trials met
      criteria for good quality. Transient stinging was a commonly noted adverse
      effect. CONCLUSIONS: Topical NSAIDs are effective analgesics for traumatic
      corneal abrasions.

PMID- 15860702
TI  - Determining the accuracy of a rapid point-of-care test for determining Rh(D)
      phenotype.
AB  - OBJECTIVES: To determine the sensitivity, specificity, and accuracy of a point-of
      care method for identifying Rh(D) phenotype. METHODS: Rh(D) was determined using
      preserved whole blood via standard laboratory methods. Comparison testing was
      conducted using the HealthTEST Rh(D) card (Akers Laboratories, Thorofare, NJ).
      Results of the card test were visually interpreted and recorded. To achieve
      sensitivity and specificity of 99% (95% confidence interval [CI] = 98% to 100%),
      380 Rh-positive and 380 Rh-negative samples were required. During card testing,
      convenience sampling was used. Card results were compared with official results,
      and statistical analysis was conducted. RESULTS: In identifying Rh(D)-positive
      phenotype, the card had a sensitivity of 98.9% and a specificity of 99.7% (95% CI
      = 0.99 +/- 0.01). For Rh(D)-negative phenotype, the card had a sensitivity of
      99.7% and a specificity of 98.9% (95% CI = 0.99 +/- 0.01). CONCLUSIONS: In
      identifying type D (Rh positive or Rh negative), the card achieves sensitivity,
      specificity, and accuracy to warrant further study.

PMID- 15860703
TI  - Family members do not disrupt care when present during invasive procedures.
AB  - OBJECTIVE: To determine whether family members (FMs) remaining with pediatric
      patients during invasive procedures interfere with delivery of care. METHODS: The
      authors conducted a prospective observational study of consecutive patients <18
      years of age undergoing invasive procedures in the emergency department (ED) over
      a one-year period. Behaviors of FMs remaining during invasive procedures were
      recorded as any of six categorical descriptions (stood quietly, asked questions,
      soothed patient, helped restrain patient, interfered with care, other). All
      observations were made through direct observation by two study attending
      physicians on FMs of patients under their direct care, or during their
      supervision of resident care. RESULTS: Fifty-four FMs were observed during the ED
      care of 37 patients [mean age 1.5 years (+/-0.25), median age 0.4 years].
      Invasive procedures included: lumbar puncture (n = 28), endotracheal intubation
      (n = 5), fracture reduction (n = 2), shoulder reduction (n = 1), and tube
      thoracostomy (n = 1). Seventy-one FM activities were recorded: stood bedside, 22
      (31%); soothed child, 21 (30%); asked questions, 11 (16%); helped restrain, 5
      (7%); interfered with care, 2 (3%); and other, 10 (15%). The two "interfered with
      care" events were minor and did not significantly alter patient management. One
      mother experienced a near-syncope event standing during a lumbar puncture of her
      child and was seated without further incident. One mother stopped reduction of a
      shoulder dislocation because she felt the pain control was inadequate even though
      the child was deeply sedated with propofol. Expected patient behavior was
      described to the mother and reduction was completed. CONCLUSIONS: In this study,
      family members remaining with children during invasive procedures were not a risk
      for disruption of patient care.

PMID- 15860704
TI  - White blood cell count intervals and likelihood ratios for appendicitis.

PMID- 15860705
TI  - Genetic association studies in Thorax.

PMID- 15860707
TI  - Peripheral muscle training in COPD: still much to learn.

PMID- 15860708
TI  - Recovery pathway of post-SARS patients.

PMID- 15860709
TI  - Circulating endothelial progenitor cells in pulmonary inflammation.

PMID- 15860710
TI  - BOHRF guidelines for occupational asthma.

PMID- 15860711
TI  - How should COPD patients exercise during respiratory rehabilitation? Comparison
      of exercise modalities and intensities to treat skeletal muscle dysfunction.
AB  - BACKGROUND: Physical exercise is an important component of respiratory
      rehabilitation because it reverses skeletal muscle dysfunction, a clinically
      important manifestation of COPD associated with reduced health-related quality of
      life (HRQL) and survival. However, there is controversy regarding the components
      of the optimal exercise protocol. A study was undertaken to systematically
      evaluate and summarise randomised controlled trials (RCTs) comparing different
      exercise protocols for COPD patients. METHODS: Six electronic databases, congress
      proceedings and bibliographies of included studies were searched without imposing
      language restrictions. Two reviewers independently screened all records and
      extracted data on study samples, interventions and methodological characteristics
      of included studies. RESULTS: The methodological quality of the 15 included RCTs
      was low to moderate. Strength exercise led to larger improvements of HRQL than
      endurance exercise (weighted mean difference for Chronic Respiratory
      Questionnaire 0.27, 95% CI 0.02 to 0.52). Interval exercise seems to be of
      similar effectiveness as continuous exercise, but there are few data on
      clinically relevant outcomes. One small RCT which included patients with mild
      COPD compared the effect of high and low intensity exercise (at 80% and 40% of
      the maximum exercise capacity, respectively) and found larger physiological
      training effects from high intensity exercise. CONCLUSIONS: Strength exercise
      should be routinely incorporated in respiratory rehabilitation. There is
      insufficient evidence to recommend high intensity exercise for COPD patients and
      investigators should conduct larger high quality trials to evaluate exercise
      intensities in patients with moderate to severe COPD.

PMID- 15860712
TI  - Polyunsaturated fatty acids improve exercise capacity in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Muscle wasting and decreased muscle oxidative capacity commonly occur
      in patients with chronic obstructive pulmonary disease (COPD). Polyunsaturated
      fatty acids (PUFA) have been shown to mediate several inflammatory and metabolic
      pathways which may be involved in the pathogenesis of muscle impairment in COPD.
      The aim of this study was to investigate the effect of PUFA modulation on
      systemic inflammation, reversal of muscle wasting, and functional status in COPD.
      METHODS: Eighty patients with COPD (57 men) with forced expiratory volume in 1
      second (FEV1) 37.3 (13.8)% predicted received 9 g PUFA or placebo daily in a
      double blind randomised fashion during an 8 week rehabilitation programme. Body
      composition (bioelectrical impedance), functional capacity (lung function,
      incremental cycle ergometry test, submaximal cycle test, isokinetic quadriceps
      strength) and inflammatory markers (C-reactive protein (CRP), interleukin (IL)-6
      and tumour necrosis factor (TNF)-alpha) were assessed at baseline and after 8
      weeks. RESULTS: Both groups had similar increases in weight, fat-free mass (FFM),
      and muscle strength. The peak load of the incremental exercise test increased
      more in the PUFA group than in the placebo group (difference in increase 9.7 W
      (95% CI 2.5 to 17.0), p = 0.009) even after adjustment for FFM. The duration of
      the constant work rate test also increased more in patients receiving PUFA
      (difference in increase 4.3 min (95% CI 0.6 to 7.9), p = 0.023). The positive
      effects of PUFA could not be attributed to a decrease in systemic levels of CRP,
      IL-6 and TNF-alpha. CONCLUSIONS: This is the first study to show beneficial
      effects of PUFA on exercise capacity in patients with COPD.

PMID- 15860713
TI  - Exhaled nitric oxide in the diagnosis of asthma: comparison with bronchial
      provocation tests.
AB  - BACKGROUND: Bronchial provocation tests such as exercise, methacholine (MCH), and
      adenosine-5'-monophosphate (AMP) challenges are used extensively in the diagnosis
      of asthma. A study was undertaken to determine whether exhaled nitric oxide (eNO)
      can be used to diagnose asthma in patients with non-specific respiratory symptoms
      and to compare this test with conventional provocation tests. METHODS: Patients
      with non-specific respiratory symptoms and normal spirometric parameters were
      included in the study. eNO was measured and exercise, MCH and AMP challenges
      performed in all subjects. Patients were defined as asthmatic based on clinical
      follow up 24 months after testing. RESULTS: Forty patients were considered
      asthmatic and 45 were not. The area under receiver operating characteristic
      curves gave values of 0.896 for eNO, 0.781 for exercise, 0.924 for MCH, and 0.939
      for AMP (p = 0.033, 0.575 and 0.085 for eNO v exercise, MCH and AMP
      respectively). From our data, a cut off value of NO > 7 ppb at a flow rate of 250
      ml/s best differentiates between asthmatics and non-asthmatics (sensitivity
      82.5%, specificity 88.9%). Optimal cut off values for other tests were exercise:
      deltaFEV1 > or = 10% (sensitivity 57.9%, specificity 100%); PC20-MCH: < or = 3
      mg/ml (sensitivity 87.5%, specificity 86.7%); and PC20-AMP: < or = 150 mg/ml
      (sensitivity 89.5%, specificity 95.6%). CONCLUSIONS: Measurement of eNO can be
      used as a safe, simple and rapid test for the diagnosis of asthma and is as good
      as bronchial provocation tests.

PMID- 15860714
TI  - Epithelial stress and structural remodelling in childhood asthma.
AB  - BACKGROUND: In adult asthma the bronchial epithelium shows high expression of the
      epidermal growth factor receptor (EGFR) and the cyclin dependent kinase
      inhibitor, p21waf, linked to ongoing stress and injury. METHODS: To determine if
      these are early markers of disease, sections of bronchial specimens obtained post
      mortem or by bronchoscopy from non-asthmatic (n = 7), moderate (n = 7), or severe
      (n = 9) asthmatic children aged 5-15 years were examined immunohistochemically.
      All severe and one moderately asthmatic children were receiving inhaled
      corticosteroids. RESULTS: The lamina reticularis of the asthmatic biopsy sections
      was found to be thicker (p = 0.01) than normal with increased deposition of
      collagen III (p = 0.007); submucosal eosinophil numbers did not differ between
      groups. As in adults, there was an asthma-related increase in epithelial EGFR
      (p<0.002) but there was no evidence of proliferation, with Ki67 being reduced (p
      = 0.001) and p21waf increased (p<0.004). The thickness of the lamina reticularis
      was significantly correlated with epithelial EGFR (rho = 0.77, p<0.001).
      CONCLUSIONS: These data provide evidence that, in asthmatic children, the
      epithelium is stressed or injured without significant eosinophilic inflammation.
      This change in the epithelial phenotype is associated with collagen deposition in
      the lamina reticularis, suggesting that the epithelial mesenchymal trophic unit
      is active early in, and may contribute to, the pathogenesis of asthma.

PMID- 15860715
TI  - Reproducibility of non-specific bronchial challenge in adults: implications for
      design, analysis and interpretation of clinical and epidemiological studies.
AB  - BACKGROUND: Poor reproducibility of an outcome measure reduces power and, in an
      independent variable, biases results. The intraclass correlation coefficient
      measures loss of power and degree of bias. Information is lacking on the
      intraclass correlation coefficient for bronchial responsiveness and factors
      affecting reproducibility. METHODS: Papers containing information on
      reproducibility of bronchial responsiveness were identified using a Medline
      search and citations. Within and between person components of variance of PD20 or
      PC20 were expressed in doubling dose or concentration units, and the intraclass
      correlation coefficient calculated when not reported. RESULTS: Results were
      extracted from 32 papers. Intraclass correlation coefficients were over 0.9 in
      short term studies of highly selected asthmatic patients, but larger and most
      long term studies had lower intraclass correlation coefficients, less than 0.5 in
      some cases, due to greater within person or lower between person variation.
      Reproducibility of dose or concentration-response slope was generally higher, but
      still less than that of forced expiratory volume in 1 second. CONCLUSIONS:
      Information is available to calculate sample size for studies with bronchial
      responsiveness as the outcome, but results when bronchial responsiveness is an
      explanatory variable may be misleading.

PMID- 15860716
TI  - Impact of severe acute respiratory syndrome (SARS) on pulmonary function,
      functional capacity and quality of life in a cohort of survivors.
AB  - OBJECTIVE: To examine the impact of severe acute respiratory syndrome (SARS) on
      pulmonary function, exercise capacity, and health-related quality of life (HRQoL)
      among survivors. METHODS: 110 survivors with confirmed SARS were evaluated at the
      Prince of Wales Hospital, HK at the end of 3 and 6 months after symptom onset.
      The assessment included lung volumes (TLC, VC, RV, FRC), spirometry (FVC, FEV1),
      carbon monoxide transfer factor (TLCO adjusted for haemoglobin), inspiratory and
      expiratory respiratory muscle strength (Pimax and Pemax), 6 minute walk distance
      (6MWD), chest radiographs, and HRQoL by SF-36 questionnaire. RESULTS: There were
      44 men and 66 women with a mean (SD) age of 35.6 (9.8) years and body mass index
      of 23.1 (4.8) kg/m2. Seventy (64%) were healthcare workers. At 6 months 33
      subjects (30%) had abnormal chest radiographs; four (3.6%), eight (7.4%), and 17
      (15.5%) patients had FVC, TLC, and TLCO below 80% of predicted values; and 15
      (13.9%) and 24 (22.2%) had Pimax and Pemax values below 80 cm H2O, respectively.
      The 6MWD increased from a mean (SD) of 464 (83) m at 3 months to 502 (95) m (95%
      CI 22 to 54 m, p<0.001), but the results were lower than normal controls in the
      same age groups. There was impairment of HRQoL at 6 months. Patients who required
      ICU admission (n = 31) had significantly lower FVC, TLC, and TLCO than those who
      did not. CONCLUSION: The exercise capacity and health status of SARS survivors
      was considerably lower than that of a normal population at 6 months. Significant
      impairment in surface area for gas exchange was noted in 15.5% of survivors. The
      functional disability appears out of proportion to the degree of lung function
      impairment and may be related to additional factors such as muscle deconditioning
      and steroid myopathy.

PMID- 15860717
TI  - Increased circulating endothelial progenitor cells in patients with bacterial
      pneumonia: evidence that bone marrow derived cells contribute to lung repair.
AB  - BACKGROUND: Tissue repair often occurs in organs damaged by various inflammatory
      diseases including pneumonia. Inflammatory stimuli induce a rapid and massive
      release of inflammatory cells from the bone marrow. Recent studies have suggested
      that bone marrow cells have the potential to differentiate into a variety of cell
      types. It has been shown that administration of lipopolysaccharide (LPS) to
      murine lungs induces a rapid release of endothelial progenitor cells (EPCs) into
      the circulation, and that bone marrow derived progenitor cells including EPCs
      contribute to lung repair after lung injury in mice. This study was undertaken to
      investigate the mobilisation of EPCs in humans following acute pneumonia.
      METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from venous
      blood taken from 23 patients with pneumonia during both the acute and
      convalescent phase. 1x10(6) PBMCs were plated on fibronectin coated culture
      slides and cultured in culture medium for endothelium. The numbers of EPCs were
      counted 8 days after plating. RESULTS: The number of circulating EPCs
      significantly increased in patients with pneumonia (p<0.0001). Patients with low
      EPC counts tended to have persistent fibrotic changes in their lungs even after
      their recovery from pneumonia. CONCLUSIONS: Inflammatory stimuli induce a rapid
      release of EPCs into the circulation in humans. A sufficient number of EPCs is
      necessary for proper lung repair following bacterial pneumonia.

PMID- 15860718
TI  - Mucociliary transport using 99mTc-albumin colloid: a reliable screening test for
      primary ciliary dyskinesia.
AB  - BACKGROUND: A study was undertaken to assess the reliability of the nasal
      mucociliary transport test using 99mTc-albumin colloid as a screening test for
      primary ciliary dyskinesia (PCD) and to compare it with the gold standard nasal
      biopsy for study of ciliary motility and ultrastructure. METHODS: During a 4 year
      period both tests were performed in 55 children referred with persistent or
      recurrent respiratory tract infections. Their median age was 4 years (range 1
      month to 15 years). RESULTS: The nasal biopsy results were as follows: PCD, n =
      8; secondary ciliary dyskinesia (SCD), n = 19; normal, n = 28. The mucociliary
      transport test was abnormal in 29 patients (all 8 with PCD, 7/19 with SCD, and
      14/28 with a normal biopsy). The sensitivity of the mucociliary transport test to
      diagnose PCD was therefore 100% (8/8) (95% exact confidence limits 63.06 to
      100.00); the specificity was only 55% (26/47) (40.95 to 69.89). The negative
      predictive value was 100% (26/26) (86.77 to 100.00) and the positive predictive
      value was 28% (8/29) (12.37 to 47.24). CONCLUSION: Mucociliary transport is a non
      invasive screening test that can be performed even in infants. The sensitivity of
      the test is high but its specificity is low. A normal test result excludes PCD.

PMID- 15860719
TI  - A simple procedure for measuring pharyngeal sensitivity: a contribution to the
      diagnosis of sleep apnoea.
AB  - BACKGROUND: Patients with severe apnoea may have an impaired pharyngeal dilating
      reflex related to decreased pharyngeal sensitivity. The accuracy of a simple new
      procedure to measure pharyngeal sensitivity and to diagnose sleep disordered
      breathing (SDB) was investigated. METHODS: Pharyngeal disappearance and
      appearance sensory perception thresholds were measured by delivering different
      airflow rates on the soft palate using an intraoral device in 17 controls and 50
      patients suffering from SDB evaluated by overnight polygraphy. The procedure was
      performed before (baseline) and after three successive administrations of a
      topical anaesthetic to sensitise the pharyngeal sensory impairment. Pharyngeal
      sensitivity was then evaluated according to SDB severity. SDB was classified as
      mild, moderate or severe according to the relative proportion of obstructive
      apnoeas-hypopnoeas and the amount of desaturation. RESULTS: Patients had higher
      baseline disappearance and appearance sensory thresholds than controls (mean (SD)
      0.62 (0.44) v 0.26 (0.06) l/min and 0.85 (0.40) v 0.40 (0.19) l/min, p<0.001,
      respectively). Such differences were enhanced by topical anaesthesia. Impairment
      of pharyngeal sensitivity and the number of patients with impaired sensitivity
      increased from the least to the most severe SDB group as indicated by the test
      sensitivity for a respiratory disturbance index of >20/hour (50%, 73.7% and 88.5%
      in the mild, moderate, and severely affected groups, respectively). CONCLUSIONS:
      This simple and safe procedure showed that impairment of pharyngeal sensitivity
      is correlated with severity of SDB. Using this test in routine clinical practice
      may simplify the diagnosis of sleep apnoea, particularly for the most severe
      patients.

PMID- 15860720
TI  - Randomised controlled crossover trial of humidified continuous positive airway
      pressure in mild obstructive sleep apnoea.
AB  - BACKGROUND: It is unclear whether continuous positive airway pressure (CPAP), the
      treatment of choice for severe obstructive sleep apnoea (OSA), is effective at
      improving outcomes in mild OSA. METHODS: To help define the role of humidified
      CPAP in mild OSA, a randomised crossover study was undertaken of patients with an
      apnoea hypopnoea index (AHI) of 5-30/hour. Subjective sleepiness, objective
      wakefulness, mood, reaction time, and quality of life were measured at baseline,
      after 3 weeks treatment with humidified CPAP and 3 weeks sham CPAP (2 week
      washout). RESULTS: Twenty nine of 31 enrolled patients (age 25-67 years, seven
      women, mean (SD) body mass index 31.5 (6) kg/m2) completed the protocol.
      Humidified CPAP improved polysomnographic indices of OSA and Epworth Sleepiness
      Scale (2.4 points (95% CI 0.6 to 4.2)). Objective wakefulness (modified
      maintenance of wakefulness test) showed a trend towards improvement (5.2 minutes
      (95% CI -0.6 to 11)). Mood (Hospital Anxiety and Depression Scale), quality of
      life (SF 36, Functional Outcomes of Sleep Questionnaire), and reaction times
      (Psychomotor Vigilance Task) were not improved more than sham CPAP. Compliance
      with humidified and sham CPAP both averaged 4.9 hours/night. Placebo effects were
      evident in many outcomes and there was no clear treatment preference.
      CONCLUSIONS: Humidified CPAP improves subjective sleepiness and possibly
      objective wakefulness but not reaction times, quality of life, or mood. These
      results do not support the routine use of CPAP in all patients with mild OSA, but
      offers some support for the trialling of CPAP in those with severe sleepiness.

PMID- 15860721
TI  - Asbestos, asbestosis, and lung cancer: a critical assessment of the
      epidemiological evidence.
AB  - The question of whether lung cancer can be attributed to asbestos exposure in the
      absence of asbestosis remains controversial. Nine key epidemiological papers are
      reviewed in a point/counterpoint format, giving the main strengths and
      limitations of the evidence presented. Of the nine papers, two concluded that
      asbestosis was necessary and seven that it was not. However, the study design,
      nature and circumstances of exposure and method of analysis of the studies
      differed considerably, and none was considered definitive. It is concluded that,
      because of the relative insensitivity of chest radiography and the uncertain
      specificity of findings from histological examinations or computed tomography, it
      is unlikely that epidemiology alone can put either the strict scientific or
      practical medicolegal questions beyond doubt. It is probable that the issue may
      depend critically on asbestos fibre type, an aspect not so far addressed.

PMID- 15860722
TI  - A patient with insidious onset of exertional dyspnoea.
AB  - The case history is presented of a 42 year old woman with pulmonary artery
      occlusion due to tuberculous vasculitis that masqueraded as chronic pulmonary
      artery embolism and led to severe life threatening haemoptysis necessitating
      emergency pneumonectomy. It is concluded that obliterative tuberculous
      endarteritis of the pulmonary arteries should be considered in the differential
      diagnosis of any acquired obstruction of pulmonary arteries.

PMID- 15860723
TI  - Burkholderia infection and survival in CF.

PMID- 15860724
TI  - Nodular pseudotumoral pulmonary amyloidosis mimicking pulmonary carcinoma.

PMID- 15860725
TI  - Nonsense-mediated mRNA decay in mammals.

PMID- 15860726
TI  - Anna El'skaya. Interview by Fiona Watt.

PMID- 15860727
TI  - Apoptosis in Drosophila: neither fish nor fowl (nor man, nor worm).
AB  - Studies in a wide variety of organisms have produced a general model for the
      induction of apoptosis in which multiple signaling pathways lead ultimately to
      activation of the caspase family of proteases. Once activated, these enzymes
      cleave key cellular substrates to promote the orderly dismantling of dying cells.
      A broad similarity exists in the cell death pathways operating in different
      organisms and there is a clear evolutionary conservation of apoptotic regulators
      such as caspases, Bcl-2 family members, inhibitor of apoptosis (IAP) proteins,
      IAP antagonists and caspase activators. Despite this, studies in Caenorhabditis
      elegans, Drosophila and vertebrates have revealed some apparent differences both
      in the way apoptosis is regulated and in the way individual molecules contribute
      to the propagation of the death signal. For example, whereas cytochrome c
      released from mitochondria clearly promotes caspase activation in vertebrates,
      there is no documented role for cytochrome c in C. elegans apoptosis and its role
      in Drosophila is highly controversial. In addition, the apoptotic potency of IAP
      antagonists appears to be greater in Drosophila than in vertebrates, indicating
      that IAPs may be of different relative importance in different organisms. Thus,
      although Drosophila, worms and humans share a host of apoptotic regulators, the
      way in which they function may not be identical.

PMID- 15860728
TI  - Single-molecule diffusion measurements of H-Ras at the plasma membrane of live
      cells reveal microdomain localization upon activation.
AB  - Recent studies show that the partitioning of the small GTPase H-Ras in different
      types of membrane microdomains is dependent on guanosine 5'-triphosphate (GTP)
      loading of H-Ras. Detailed knowledge about the in vivo dynamics of this
      phenomenon is limited. In this report, the effect of the activation of H-Ras on
      its microdomain localization was studied by single-molecule fluorescence
      microscopy. Individual human H-Ras molecules fused to the enhanced yellow
      fluorescent protein (eYFP) were imaged in the dorsal plasma membrane of live
      mouse cells and their diffusion behavior was analyzed. The diffusion of a
      constitutively inactive (S17N) and constitutively active (G12V) mutant of H-Ras
      was compared. Detailed analysis revealed that for both mutants a major, fast
      diffusing population and a minor, slow-diffusing population were present. The
      slow-diffusing fraction of the active mutant was confined to 200 nm domains,
      which were not observed for the inactive mutant. In line with these results we
      observed that the slow-diffusing fraction of wild-type H-Ras became confined to
      200 nm domains upon insulin-induced activation of wild-type H-Ras. This
      activation-dependent localization of H-Ras to 200 nm domains, for the first time
      directly detected in live cells, supports the proposed relationship between H-Ras
      microdomain localization and activation.

PMID- 15860729
TI  - Grp/DChk1 is required for G2-M checkpoint activation in Drosophila S2 cells,
      whereas Dmnk/DChk2 is dispensable.
AB  - Cell-cycle checkpoints are signal-transduction pathways required to maintain
      genomic stability in dividing cells. Previously, it was reported that two kinases
      essential for checkpoint signalling, Chk1 and Chk2 are structurally conserved. In
      contrast to yeast, Xenopus and mammals, the Chk1- and Chk2-dependent pathways in
      Drosophila are not understood in detail. Here, we report the function of these
      checkpoint kinases, referred to as Grp/DChk1 and Dmnk/DChk2 in Drosophila
      Schneider's cells, and identify an upstream regulator as well as downstream
      targets of Grp/DChk1. First, we demonstrate that S2 cells are a suitable model
      for G(2)/M checkpoint studies. S2 cells display Grp/DChk1-dependent and
      Dmnk/DChk2-independent cell-cycle-checkpoint activation in response to
      hydroxyurea and ionizing radiation. S2 cells depleted for Grp/DChk1 using RNA
      interference enter mitosis in the presence of impaired DNA integrity, resulting
      in prolonged mitosis and mitotic catastrophe. Grp/DChk1 is phosphorylated in a
      Mei-41/DATR-dependent manner in response to hydroxyurea and ionizing radiation,
      indicating that Mei-41/ATR is an upstream component in the Grp/DChk1 DNA
      replication and DNA-damage-response pathways. The level of Cdc25(Stg) and
      phosphorylation status of Cdc2 are modulated in a Grp/DChk1-dependent manner in
      response to hydroxyurea and irradiation, indicating that these cell-cycle
      regulators are downstream targets of the Grp/DChk1-dependent DNA replication and
      DNA-damage responses. By contrast, depletion of Dmnk/DChk2 by RNA interference
      had little effect on checkpoint responses to hydroxyurea and irradiation. We
      conclude that Grp/DChk1, and not Dmnk/DChk2, is the main effector kinase involved
      in G(2)/M checkpoint control in Drosophila cells.

PMID- 15860730
TI  - BCL6 suppresses RhoA activity to alter macrophage morphology and motility.
AB  - BCL6 is a potent transcriptional repressor that plays important roles in germinal
      center formation, T helper cell differentiation and lymphomagenesis and regulates
      expression of several chemokine genes in macrophages. In a further investigation
      of its role in macrophages, we show that BCL6 inactivation in primary bone marrow
      derived macrophages leads to decreased polarization, motility and cell spreading
      accompanied by an increase in peripheral focal complexes, anchored F-actin
      bundles and cortical F-actin density. These changes were associated with excess
      RhoA activation. C3 transferase inhibition of RhoA activity reverted the adhesion
      structure phenotype, which was not affected by Rho kinase inhibitors, suggesting
      that other downstream effectors of Rho maintain this Bcl6(-/-) phenotype. Excess
      RhoA activation in BCL6-deficient macrophages is associated with a decrease in
      the p120RasGAP (RASA1)-mediated translocation of p190RhoGAP (GRLF1) to active
      RhoA at the plasma membrane and a reduction in cell surface expression of the
      CSF1R that has been reported to recruit RasGAP to the plasma membrane.
      Reconstitution of BCL6 expression in Bcl6(-/-) macrophages results in complete
      reversion of the morphological phenotype and a significant increase in cell
      surface CSF1R expression whereas overexpression of the CSF1R corrects the
      polarization and adhesion structure defects. These results demonstrate that BCL6
      suppresses RhoA activity, largely through upregulation of surface CSF1R
      expression, to modulate cytoskeletal and adhesion structures and increase the
      motility of macrophages.

PMID- 15860731
TI  - Vglut1 and ZnT3 co-targeting mechanisms regulate vesicular zinc stores in PC12
      cells.
AB  - The lumenal ionic content of an organelle is determined by its complement of
      channels and transporters. These proteins reach their resident organelles by
      adaptor-dependent mechanisms. This concept is illustrated in AP-3 deficiencies,
      in which synaptic vesicle zinc is depleted because the synaptic-vesicle-specific
      zinc transporter 3 does not reach synaptic vesicles. However, whether zinc
      transporter 3 is the only membrane protein defining synaptic-vesicle zinc content
      remains unknown. To address this question, we examined whether zinc transporter 3
      and the vesicular glutamate transporter Vglut1 (a transporter that coexists with
      zinc transporter 3 in brain nerve terminals) were co-targeted to synaptic-like
      microvesicle fractions in PC12 cells. Deconvolution microscopy and subcellular
      fractionation demonstrated that these two transporters were present on the same
      vesicles in PC12 cells. Vglut1 content in synaptic-like microvesicle fractions
      and brain synaptic vesicles was partially sensitive to pharmacological and
      genetic perturbation of AP-3 function. Whole-cell flow-cytometry analysis of PC12
      cell lines expressing zinc transporter 3, Vglut1 or both showed that vesicular
      zinc uptake was increased by Vglut1 expression. Conversely, production of zinc
      transporter 3 increased the vesicular uptake of glutamate in a zinc-dependent
      fashion. Our results suggest that the coupling of zinc transporter 3 and Vglut1
      transport mechanisms regulates neurotransmitter content in secretory vesicles.

PMID- 15860732
TI  - 14-3-3 and calmodulin control subcellular distribution of Kir/Gem and its
      regulation of cell shape and calcium channel activity.
AB  - Individual members of the RGK family of Ras-related GTPases, which comprise Rad,
      Gem/Kir, Rem and Rem2, have been implicated in important functions such as the
      regulation of voltage-gated calcium channel activity and remodeling of cell
      shape. The GTPase Kir/Gem inhibits the activity of calcium channels by
      interacting with the beta-subunit and also regulates cytoskeleton dynamics by
      inhibiting the Rho-Rho kinase pathway. In addition, Kir/Gem interacts with 14-3-3
      and calmodulin, but the significance of this interaction on Kir/Gem function is
      poorly understood. Here, we present a comprehensive analysis of the binding of 14
      3-3 and calmodulin to Kir/Gem. We show that 14-3-3, in conjunction with
      calmodulin, regulates the subcellular distribution of Kir/Gem between the
      cytoplasm and the nucleus. In addition, 14-3-3 and calmodulin binding modulate
      Kir/Gem-mediated cell shape remodeling and downregulation of calcium channel
      activity. Competition experiments show that binding of 14-3-3, calmodulin and
      calcium channel beta-subunits to Kir/Gem is mutually exclusive, providing a
      rationale for the observed regulatory effects of 14-3-3 and calmodulin on Kir/Gem
      localization and function.

PMID- 15860733
TI  - A role for cathepsin E in the processing of mast-cell carboxypeptidase A.
AB  - Mast-cell carboxypeptidase A is stored in the secretory granule and is released,
      together with a range of other inflammatory mediators, upon mast-cell
      degranulation. Carboxypeptidase A, like all mast-cell proteases, is stored in the
      granule as an active enzyme (i.e. with its propeptide removed). Although the
      processing mechanisms for the other classes of mast-cell proteases (in particular
      the chymases) have been clarified to some extent, the processing of
      procarboxypeptidase A is poorly characterized. Here, we show that mast cells from
      mice lacking the aspartic protease cathepsin E display an accumulation of
      procarboxypeptidase A, indicating a defect in carboxypeptidase-A processing. By
      contrast, mast cells lacking cathepsins B, L or D have normal carboxypeptidase-A
      processing. Furthermore, recombinant cathepsin E was found to process recombinant
      procarboxypeptidase A in vitro, under conditions resembling those found in mast
      cell granules. Immunohistochemical analysis revealed staining for cathepsin E in
      mast cells from normal mice but not in mast cells from mice lacking heparin,
      indicating that cathepsin E is bound to heparin proteoglycan within mast-cell
      granules. In accordance with this notion, affinity chromatography showed that
      recombinant cathepsin E bound strongly to heparin under acidic conditions (the
      conditions prevailing in mast-cell granules) but not at neutral pH. Moreover,
      mast-cell degranulation resulted in the release of cathepsin E. Taken together,
      our results indicate that cathepsin E is located in mast-cell secretory granules
      in complex with heparin proteoglycans, and that it has a role in the processing
      of procarboxypeptidase A into active protease.

PMID- 15860734
TI  - Binding and internalization of C-reactive protein by Fcgamma receptors on human
      aortic endothelial cells mediates biological effects.
AB  - OBJECTIVE: In addition to being a cardiovascular risk marker, recent studies
      support a role for CRP in atherothrombosis. Several investigators have reported
      that CRP binds to Fcgamma receptors on leukocytes. The aim of the study is to
      determine the processing of CRP by human aortic endothelial cells (HAECs).
      METHODS AND RESULTS: Binding studies were performed by incubation of HAECs with
      biotinylated CRP (B-CRP, 25 to 200 microg/mL) for 30 to 180 minutes at 4 degrees
      C. B-CRP binding was quantitated using streptavidin-fluorescein isothiocyanate
      followed by flow cytometry. Saturable binding of CRP was obtained at 60 minutes
      with a CRP concentration between 100 to 150 microg/mL and Kd of 88 nM. CRP
      binding was inhibited by 10x cold CRP (58%). CRP (100 microg/mL) significantly
      upregulated surface expression of Fcgamma receptors, CD32, as well as CD64 on
      HAECs (P<0.01). Also, preincubation with anti-CD32 and CD64 antibodies
      significantly inhibited maximal binding of CRP to HAECs 64% and 30%,
      respectively, whereas antibodies to CD16 had no effect. Internalization of CRP,
      as determined by loss of surface expression, was 50%. Also, binding and
      internalization of biotinylated CRP was confirmed by confocal microscopy and CRP
      colocalized with CD32 and CD64. Most importantly, the increase in interleukin-8,
      intercellular adhesion molecule 1, and vascular cell adhesion molecule-1 and the
      decrease in eNOS and prostacyclin induced by CRP was abrogated with antibodies to
      CD32 and CD64. CONCLUSIONS: We demonstrate that CRP mediates its biological
      effects on HAECs via binding and internalization through Fcgamma receptors, CD32
      and CD64.

PMID- 15860735
TI  - Signal transducer and activator of transcription 3alpha and specificity protein 1
      interact to upregulate intercellular adhesion molecule-1 in ischemic-reperfused
      myocardium and vascular endothelium.
AB  - OBJECTIVE: Intercellular adhesion molecule-1 (ICAM-1) is upregulated rapidly on
      endothelial cells during ischemia-reperfusion (I-R) and mediates tissue leukocyte
      accumulation. The ICAM-1 proximal promoter contains a signal transducer and
      activator of transcription (Stat) binding motif (gamma-interferon activation site
      [GAS] sequence), which flanks a specificity protein 1 (Sp1) binding site. We
      examined the roles of Stat and Sp1 in the regulation of ICAM-1 after myocardial I
      R. METHODS AND RESULTS: Open-chest anesthetized rats underwent coronary artery
      occlusion for 35 minutes and reperfusion for 0 to 240 minutes. Stat became
      activated within 15 minutes after reperfusion, primarily in vascular endothelial
      cells; the activated Stat protein was identified as Stat3 (alpha-isoform). After
      phosphorylation on serine 727 (p-S727), Stat3alpha was found in association with
      the transcriptional regulator Sp1, and the complex bound to an ICAM-1-GAS probe.
      ICAM-1 expression increased after I-R and lagged shortly behind Stat3alpha
      activation. In cultured human umbilical vein endothelial (HUVE) cells, activation
      of Stat3alpha after hypoxia-reoxygenation (H-R) was dependent on the small GTPase
      Rac1. Transfection of a dominant-negative Stat3 (Y705F) adenovirus or a GAS decoy
      oligonucleotide reduced ICAM-1 mRNA expression after H-R. Using a reporter gene
      transfected into HUVE cells, mutation of the GAS element in the ICAM-1 promoter
      resulted in reduced transcriptional activity after H-R. Sp1 coimmunoprecipitated
      with p-S727 Stat3 during H-R, and Sp1 or Stat3alpha interfering RNA markedly
      reduced ICAM-1 mRNA expression. CONCLUSIONS: The Sp1-Stat3 complex appears to
      play an important role in the upregulation of ICAM-1 transcription after
      reoxygenation or reperfusion.

PMID- 15860736
TI  - Regulation of blood coagulation by the protein C anticoagulant pathway: novel
      insights into structure-function relationships and molecular recognition.
AB  - The protein C system provides important control of blood coagulation by
      regulating the activities of factor VIIIa (FVIIIa) and factor Va (FVa), cofactors
      in the activation of factor X and prothrombin, respectively. The system comprises
      membrane-bound and circulating proteins that assemble into multi-molecular
      complexes on cell surfaces. Vitamin K-dependent protein C, the key component of
      the system, circulates in blood as zymogen to an anticoagulant serine protease.
      It is efficiently activated on the surface of endothelial cells by thrombin bound
      to the membrane protein thrombomodulin. The endothelial protein C receptor (EPCR)
      further stimulates the protein C activation. Activated protein C (APC) together
      with its cofactor protein S inhibits coagulation by degrading FVIIIa and FVa on
      the surface of negatively charged phospholipid membranes. Efficient FVIIIa
      degradation by APC requires not only protein S but also intact FV, which like
      thrombin is a Janus-faced protein with both procoagulant and anticoagulant
      potential. In addition to its anticoagulant properties, APC has antiinflammatory
      and antiapoptotic functions, which are exerted when APC binds to EPCR and
      proteolytic cleaves protease-activated receptor 1 (PAR-1). The protein C system
      is physiologically important, and genetic defects affecting the system are the
      most common risk factors of venous thrombosis. The proteins of the protein C
      system are composed of multiple domains and the 3-dimensional structures of
      several of the proteins are known. The molecular recognition of the protein C
      system is progressively being unraveled, giving us new insights into this
      fascinating and intricate molecular scenario at the atomic level.

PMID- 15860737
TI  - Rac1 regulation of surface expression of protease-activated receptor-1 and
      responsiveness to thrombin in vascular smooth muscle cells.
AB  - OBJECTIVE: Protease-activated receptor-1 (PAR1) mediates the thrombin-induced
      proliferation and hypertrophy of vascular smooth muscle cells. A role of Rac1 in
      the regulation of PAR1 expression was investigated. METHODS AND RESULTS:
      Treatment with simvastatin, a hydroxy-3-methyl-glutaryl coenzyme A reductase
      inhibitor, for 24 hours attenuated the transient [Ca2+]i elevation induced by
      thrombin. Immunofluorescence staining revealed that simvastatin decreased the
      surface expression of PAR1 in a manner dependent on protein geranylgeranylation.
      Introduction of a Rac1/Cdc42 inhibitory fragment but not a RhoA inhibitory
      fragment using a cell-penetrating peptide also attenuated the response to
      thrombin and decreased the surface expression of PAR1. Finally, downregulation of
      Rac1, but not RhoA, using an RNA interference technique attenuated the thrombin
      induced [Ca2+]i elevation. However, the level of PAR1 mRNA and the total amount
      of PAR1 protein remained unchanged. CONCLUSIONS: Here, we provide for the first
      time 3 lines of evidence that Rac1 plays a critical role in maintaining the
      surface expression of PAR1 and the responsiveness to thrombin in vascular smooth
      muscle cells. Rac1 is suggested to regulate the constitutive trafficking of PAR1
      and thereby regulate the surface expression of PAR1.

PMID- 15860738
TI  - Associations of serum IL-18 levels with carotid intima-media thickness.
AB  - OBJECTIVE: Elevated circulating levels of IL-18 can predict future coronary heart
      disease. Although IL-18 is thought to play a crucial role in atherosclerosis,
      whether circulating IL-18 levels are associated with the severity of
      atherosclerosis remains to be determined. With the use of B-mode ultrasound, this
      study examines the relationships of serum IL-18 levels with carotid intima-media
      thickness (IMT) as a reflector for systemic atherosclerosis. METHODS AND RESULTS:
      The study comprised 366 patients without histories of cardiovascular accidents.
      Severity of carotid atherosclerosis was evaluated by the mean max IMT, ie, mean
      of the maximal wall thickness at 12 carotid segments. Serum IL-18, IL-6, and high
      sensitive C-reactive protein (hs-CRP) levels were determined in all patients. Log
      transformed IL-18 concentrations were positively correlated with IMT (r=0.36,
      P<0.001), and the association remained significant (beta=0.20, P<0.001) when
      controlling for traditional atherosclerotic risk factors, IL-6 and hs-CRP levels.
      Also, IMT was greater in the highest and the middle tertile of IL-18 levels than
      in the lowest tertile. CONCLUSIONS: Higher serum IL-18 levels appear to be
      associated with greater carotid IMT, suggesting the link between IL-18 and
      atherosclerosis.

PMID- 15860739
TI  - Genotype and plasma concentration of cystatin C in patients with coronary heart
      disease and risk for secondary cardiovascular events.
AB  - OBJECTIVE: Cysteine proteases and their inhibitors such as cystatin C are assumed
      to play an important role in the pathogenesis of atherosclerosis and coronary
      heart disease (CHD). The aim of the study was to investigate the impact of
      cystatin C polymorphisms on cystatin C plasma levels and on prognosis of patients
      with CHD. METHODS AND RESULTS: Four polymorphisms in the promoter and exon 1 of
      the cystatin C gene (-82GC, -5GA, +4AC, and +148AG) and cystatin C plasma levels
      were determined in a cohort of 1013 patients with manifest CHD and aged 30 to 70
      years participating in an in-hospital rehabilitation program. Patients were
      followed-up for a mean of 33.5 months and a combined end point (fatal and
      nonfatal cardiovascular disease [CVD] events) was used as the outcome variable.
      The major haplotype -82G/-5G/+4A was associated with cystatin C plasma levels
      with persons homozygous for the major haplotype having the highest levels
      (P=0.01). However, the haplotype was not associated with fatal and nonfatal
      cardiovascular events during the 3-year follow-up. CONCLUSIONS: The major
      haplotype -82G/-5G/+4A of the cystatin C gene determines plasma levels of
      cystatin C with homozygous persons having the highest plasma levels, but there
      was no association with secondary CVD events in this study.

PMID- 15860740
TI  - Smad7 gene transfer attenuates adventitial cell migration and vascular remodeling
      after balloon injury.
AB  - OBJECTIVE: Migration of adventitial fibroblasts contributes to arterial
      remodeling after angioplasty. This study used vascular gene transfer of smad7 to
      investigate whether antagonism of transforming growth factor-beta1 signaling
      alters luminal loss and adventitial cell migration after balloon injury in rat
      carotid arteries. METHODS AND RESULTS: Adenoviruses coordinating expression of
      beta-galactosidase (beta-gal) and smad7 or beta-gal and green fluorescent protein
      (GFP) were applied to the perivascular surface of common carotid arteries.
      Balloon injury was performed 4 days after gene transfer, and animals were killed
      at 3, 7, and 14 days after injury. Uninjured arteries only expressed adventitial
      beta-gal positive cells; however, after balloon injury in beta-gal- and GFP
      transfected arteries, beta-gal-positive cells were observed within the medial
      layer of vessels and contributed to the population of cells within the neointima
      at 7 to 14 days. Overexpression of smad7 and beta-gal resulted in a significant
      reduction in the number of beta-gal-labeled cells in the neointima, concomitant
      with reduced luminal loss and decreased adventitial collagen content.
      CONCLUSIONS: We provide the first evidence that vascular smad7 overexpression
      attenuates remodeling and contribution of adventitial fibroblasts to neointima
      formation after balloon angioplasty. Smad7 may represent a novel therapeutic
      target to reduce the incidence of restenosis.

PMID- 15860741
TI  - Asymmetrical dimethylarginine in idiopathic pulmonary arterial hypertension.
AB  - OBJECTIVE: We explored the potential role of the endogenous NO synthase inhibitor
      asymmetrical dimethylarginine (ADMA) in patients with idiopathic pulmonary
      arterial hypertension (IPAH). Method and Results- We correlated plasma ADMA
      levels and cardiovascular indices from right heart catheterization in 57 patients
      with IPAH. Predictors of survival in patients with IPAH were studied.
      Furthermore, the effect of systemic ADMA infusion on pulmonary ventricular
      resistance and stroke volume was investigated in healthy volunteers using right
      heart catheterization. Mean plasma ADMA concentrations were significantly higher
      in patients with IPAH than in control subjects (0.53+/-0.15 versus 0.36+/-0.05
      micromol/L; P<0.001). ADMA plasma concentrations correlated significantly with
      indices of right ventricular function, such as mixed-venous oxygen saturation (r=
      0.49; P<0.0001), right atrial pressure (r=0.39; P<0.003), cardiac index (r=-0.35;
      P<0.008), as well as survival (r=-0.47; P<0.0001). Multiple regression analysis
      revealed that right atrial pressure (r=0.31; P<0.026) and ADMA (r=0.29; P<0.039)
      were independent predictors of mortality. Moreover, patients with supra-median
      plasma ADMA levels had significantly (P<0.021) worse survival than patients with
      infra-median ADMA values. ADMA infusion in healthy volunteers increased pulmonary
      vascular resistance (68.9+/-7.6 versus 95.6+/-6.3 dyne x s x cm(-5); P<0.05) and
      decreased stroke volume (101.1+/-6.7 mL versus 95.6+/-6.3 mL; P<0.05).
      CONCLUSIONS: Increased ADMA plasma levels are associated with unfavorable
      pulmonary hemodynamics and worse outcome in patients with IPAH.

PMID- 15860742
TI  - Intracellular and surface distribution of monocyte tissue factor: application to
      intersubject variability.
AB  - OBJECTIVE: The high and low responder phenomenon describes individual differences
      in lipopolysaccharide (LPS)-induced monocyte tissue factor (TF) activity. We
      characterized patterns of intracellular accumulation, externalization, and
      shedding of TF in response to LPS in mononuclear cells (MNCs) from high
      responders (HRs) and low responders (LRs). METHODS AND RESULTS: After 2 hours of
      LPS stimulation of whole blood, flow cytometry analyses revealed a larger
      population of TF-positive monocytes in HRs (32.0+/-3.5%) versus LRs (11.2+/-1.2%;
      P< or =0.05), along with a stronger mean fluorescence intensity of TF signal in
      HRs (7.1+/-0.5 arbitrary units [AU]) compared with LRs (5.4+/-0.4 AU; P< or
      =0.05). The LPS-treated blood of the HR group contained 2-fold more TF-positive
      microparticles than LRs. In-cell Western assay demonstrated higher intracellular
      accumulation of TF in mononuclear cells (MNCs) from LRs because LPS induced a 3.7
      fold increase of total TF levels in LRs versus a 1.5-fold increase in HRs. In
      contrast, in response to LPS stimulation, MNCs from HRs exhibited a 4-fold
      induction of surface TF, whereas MNCs from LRs only had a minor increase in
      surface TF levels. CONCLUSIONS: The higher availability of surface TF antigen on
      MNCs from HRs and TF-containing microparticles might make these individuals more
      susceptible to hypercoagulation.

PMID- 15860743
TI  - Elastin-derived peptides induce a T-helper type 1 polarization of human blood
      lymphocytes.
AB  - OBJECTIVE: Increased level of elastin-derived peptides (EDPs) is observed in the
      serum of patients with manifestations of arterial diseases. We here investigated
      whether EDPs might exert, at systemic level, a regulatory role for the T-helper
      type 1 (Th-1)/Th-2 cellular immune response by human peripheral blood lymphocytes
      (PBLs) expressing the spliced-galactosidase (S-gal)-elastin receptor. METHODS AND
      RESULTS: Using flow cytometry and Western blot analysis, we demonstrated that
      EDPs led to an activation of the S-gal-elastin receptor associated with cytokine
      production on PBLs and CD4+ T cell subpopulations. The constitutive expression of
      the S-gal-elastin receptor at the surface of human PBLs was upregulated at the
      mRNA (RT-PCR) and protein (ELISA) levels on cell activation. In nonactivated and
      phytohemagglutinin-activated conditions, expressions of the predominant Th-2
      cytokine interleukin-5 (IL-5) and IL-10 were reduced, whereas those of the major
      Th-1 cytokines interferon-gamma and IL-2 were enhanced by EDPs. Furthermore, we
      evidenced that EDPs could not only potentiate the IL-12-induced Th-1 profile but
      also could reverse the Th-2 (over Th-1) profile induced by IL-4. Finally, Th-1
      cytokine upregulation was associated to an increased activator protein-1 DNA
      binding and enhanced pro-matrix metalloproteinase-9 secretion. CONCLUSIONS: This
      study highlights the importance of EDPs as stimuli for Th-1 differentiation,
      whether T cells are in an inactivated state or already orientated toward a Th-1
      (IL-12) or Th-2 (IL-4) response.

PMID- 15860744
TI  - NADPH oxidase-dependent superoxide production is associated with carotid intima
      media thickness in subjects free of clinical atherosclerotic disease.
AB  - OBJECTIVE: Oxidative stress plays a critical role in the pathogenesis of
      atherosclerosis. The NADPH oxidase constitutes the main source of superoxide in
      phagocytic and vascular cells. This study aimed to investigate the levels of
      NADPH oxidase-mediated superoxide production in phagocytic cells and the
      association between phagocytic superoxide production and carotid intima-media
      thickness (IMT), a surrogate marker of asymptomatic atherosclerosis. METHODS AND
      RESULTS: NADPH oxidase-mediated superoxide production was determined by a
      chemiluminescence assay using lucigenin and associated with IMT for 184
      asymptomatic subjects free of overt clinical atherosclerotic disease. Compared
      with individuals in the lowest tertile of superoxide production, those in the
      upper tertile (>20 counts/sec) showed significantly higher IMT (P<0.05). In
      correlation analysis, a positive relationship was found between superoxide
      production and carotid IMT. Superoxide production also correlated positively
      (P<0.05) with body mass index (BMI). In multivariate analysis, the association of
      superoxide production with carotid IMT remained significant after adjustment for
      age, sex, systolic blood pressure, BMI, triglycerides, glucose, and smoking.
      CONCLUSIONS: In a population sample of adults without clinically overt
      atherosclerotic disease, increased NADPH oxidase activity was associated with
      enhanced carotid IMT, suggesting a relationship between phagocytic NADPH oxidase
      mediated oxidative stress and the development of atherosclerosis.

PMID- 15860745
TI  - Statins decrease Toll-like receptor 4 expression and downstream signaling in
      human CD14+ monocytes.
AB  - OBJECTIVE: Anti-inflammatory effects of statins contribute to their clinical
      benefit. Molecular mechanisms underlying these effects have not been well
      explored. Because statins attenuate lipopolysaccharide (LPS) responsiveness, we
      hypothesized that part of the pleiotropic effects are mediated through innate
      immunity. METHODS AND RESULTS: Toll-like receptor (TLR) 4 expression and
      downstream signaling in CD14+ monocytes after incubation with simvastatin and
      atorvastatin were quantified via flow-cytometry, quantitative RT-PCR, kinase
      assay, and enzyme-linked immunosorbent assay. Incubation with intermediates/
      inhibitors of the mevalonate pathway was used to identify the mode of statin
      action. Statin incubation resulted in a dose-dependent reduction of TLR4
      expression (53+/-7.6% reduction compared with untreated monocytes; P<0.005),
      transcript levels (68+/-6.3%; P<0.002), decreased IRAK phosphorylation (37+/
      8.3%; P<0.05), and LPS-induced IL-6, IL-12, tumor necrosis factor (TNF)-alpha,
      and B7-1 expression (P<0.05). Four weeks of treatment with atorvastatin
      significantly reduced TLR4 expression on circulating CD14+ monocytes by 36.2+/
      4.2% (P<0.05). Effects of statins were reversed by mevalonate (P=0.57).
      Incubation with specific inhibitors of geranylgeranyltransferase (54+/-4.3%),
      farnesyltransferase (57+/-5.1%), or with clostridium-difficile toxin B (58+/
      6.1%, P<0.01) imitated the statin effects. Whereas wortmannin and LY294002
      inhibited the statin effect (P=0.27), incubation with a specific RhoA kinase
      inhibitor had no effect (P=0.57). CONCLUSIONS: Statins influence TLR4 expression
      and signaling via inhibition of protein geranylgeranylation and farnesylation.
      These observations imply interactions with innate immunity as one pleiotropic
      mechanism.

PMID- 15860746
TI  - Niche-dependent translineage commitment of endothelial progenitor cells, not cell
      fusion in general, into myocardial lineage cells.
AB  - OBJECTIVE: Previous studies from our laboratory have shown therapeutic potential
      of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial ischemia.
      Our purpose was to investigate the mechanisms regulating EPC contribution to
      myocardial regeneration. METHODS AND RESULTS: To evaluate niche-dependent
      expression profiles of EPCs in vitro, we performed coculture using cultured EPCs
      derived from human peripheral blood and rat cardiac myoblast cell line (H9C2).
      Reverse-transcription polymerase chain reaction (PCR) disclosed the expression of
      human-specific cardiac markers as well as human-specific smooth muscle markers.
      Cytoimmunochemistry presented several cocultured cells stained with human
      specific cardiac antibody. To prove this translineage differentiation in vivo,
      human cultured EPCs were injected into nude rat myocardial infarction model.
      Reverse-transcription PCR as well as immunohistochemistry of rat myocardial
      samples demonstrated the expression of human specific cardiac, vascular smooth
      muscle, and endothelial markers. We observed the distribution of colors
      (Qtracker; Quantum Dot Corp) in coculture to detect the fused cells, and the
      frequency of cell fusion was <1%. CONCLUSIONS: EPCs can contribute to not only
      vasculogenesis but also myogenesis in the ischemic myocardium in vivo.
      Transdifferentiation, not cell fusion, is dominant for EPCs commitment to
      myocardial lineage cells. Ex vivo expanded EPCs transplantation might have
      enhanced therapeutic potential for myocardial regeneration.

PMID- 15860747
TI  - Carotid artery stenting: meeting the recruitment challenge of a clinical trial.

PMID- 15860749
TI  - Blood pressure reduction for vascular risk: is there a price to be paid?
AB  - The importance of lowering blood pressure (BP) in hypertensive subjects is well
      known and recent studies suggest that lowering of BP in patients who may already
      be in the normotensive range further reduces the risk of vascular events,
      particularly stroke. Epidemiological data have also shown that lower BP and
      antihypertensive treatment may be associated with cognitive impairment once
      cerebrovascular disease is established. However, the relationship between
      hypertension and cerebrovascular disease is more complex than suggested by
      epidemiological or intervention studies. Cerebral imaging studies have shown that
      cerebral blood flow (CBF) is reduced in areas of small-vessel disease (SVD) and
      the degree of hypoperfusion correlates with disease severity. Furthermore,
      impaired neuropsychological performance has been found to correlate with cerebral
      hypoperfusion in patients with established SVD. These findings raise questions
      surrounding the desirability of lowering of BP beyond a certain level in such
      patients. It is conceivable that indiscriminate BP reduction may compromise
      cerebral perfusion and function in these patients, increasing the risk of
      cognitive decline and cerebrovascular disease progression. Randomized clinical
      trials addressing the relationship between antihypertensive treatment and
      vascular cognitive impairment are lacking. Further studies are therefore needed
      to assess the cognitive consequences of BP reduction in people with established
      cerebrovascular disease. This will help to direct appropriate protective
      strategies and treatments in a vulnerable group of people, many of whom have
      hypertension and cerebrovascular disease at the same time.

PMID- 15860751
TI  - Ethambutol ocular toxicity in treatment regimens for Mycobacterium avium complex
      lung disease.
AB  - Ethambutol (EMB) is an important component of multidrug treatment regimens for
      Mycobacterium avium complex lung disease. Ocular toxicity is the most important
      potential EMB toxicity, especially in the elderly population with M. avium
      complex lung disease. Two hundred twenty-nine patients with M. avium complex lung
      disease, 55% women and 53% with nodular/bronchiectatic disease, received a mean
      of 16.1 +/- 10.8 months of multidrug therapy that included EMB. Fifty patients
      (22%) were known to have preexisting ocular disease. While on EMB, 97 (42%)
      patients consulted an opthalmologist and 24 (10%) stopped EMB at least
      temporarily. Eight of 139 patients (6%) on daily therapy were diagnosed with EMB
      ocular toxicity, whereas 0 of 90 patients on intermittent therapy had EMB ocular
      toxicity (p = 0.05). All patients with EMB ocular toxicity developed symptoms
      between outpatient clinic appointments; none were diagnosed with routine visual
      acuity and color vision testing. All patients with EMB ocular disease returned to
      baseline ocular status after discontinuation of EMB. Intermittent EBM
      administration was associated with less ocular toxicity than daily EMB
      administration in this patient population.

PMID- 15860752
TI  - Sleep-disordered breathing in newborn mice heterozygous for the transcription
      factor Phox2b.
AB  - RATIONALE: Central congenital hypoventilation syndrome (CCHS) is a rare autosomal
      dominant syndrome present from birth, and characterized by depressed ventilation
      during sleep. Heterozygous mutations of the homeobox gene Phox2b were recently
      found in a very high proportion of patients. OBJECTIVES: To determine whether
      newborn mice with heterozygous targeted deletion of the transcription factor
      Phox2b would display sleep-disordered breathing. METHODS: We measured breathing
      pattern using whole-body plethysmography in wild-type and mutant 5-day-old mice,
      and we classified sleep-wake states using nuchal EMG and behavioral scores.
      RESULTS: We found that sleep apnea total time was approximately six times longer
      (8.9 +/- 12 vs. 1.5 +/- 2.2 seconds, p < 0.0015), and ventilation during active
      sleep was 21% lower (18.4 +/- 5.1 vs. 23.3 +/- 5.5 ml/g/second, p < 0.006) in
      mutant than in wild-type pups. During wakefulness, apnea time and ventilation
      were not significantly different between mutant and wild-type pups. Mutant and
      wild-type pups showed highly similar sleep-wake states. CONCLUSION: Although
      their respiratory phenotype was much less severe than CCHS, the Phox2b(+/-)
      mutant mice showed sleep-disordered breathing, which partially modeled the key
      feature of CCHS.

PMID- 15860753
TI  - Glucocorticoid receptor nuclear translocation in airway cells after inhaled
      combination therapy.
AB  - Clinical evidence is accumulating for the efficacy of adding inhaled long-acting
      beta(2)-agonists (LABAs) to corticosteroids in asthma. Corticosteroids bind to
      cytoplasmic glucocorticoid receptors (GRs), which then translocate to the nucleus
      where they regulate gene expression. This article reports the first evidence in
      vivo of an interaction between inhaled LABA and corticosteroid on GR nuclear
      translocation in human airway cells using immunocytochemistry. We initially
      demonstrated significant GR activation 60 minutes after inhalation of 800 microg
      beclomethasone dipropionate in six healthy subjects. Subsequently, we determined
      the effects of salmeterol and fluticasone propionate (FP) in seven steroid-naive
      patients with asthma. We observed dose-dependent GR activation with 100- and 500
      microg doses of FP, and to a lesser extent with 50 microg salmeterol alone.
      However, combination therapy with 100 microg FP and salmeterol augmented the
      action of FP on GR nuclear localization. In vitro, salmeterol enhanced FP effects
      on GR nuclear translocation in epithelial and macrophage-like airway cell lines.
      In addition, salmeterol in combination with FP enhanced glucocorticoid response
      element (GRE)-luciferase reporter gene activity and mitogen-activated protein
      kinase phosphatase 1 (MKP-1) and secretory leuko-proteinase inhibitor (SLPI) gene
      induction. Together, our data confirm that GR nuclear translocation may underlie
      the complementary interactions between LABAs and corticosteroids, although the
      precise signal transduction mechanisms remain to be determined.

PMID- 15860754
TI  - Occupational asthma.
AB  - Substantial epidemiologic and clinical evidence indicates that agents inhaled at
      work can induce asthma. In industrialized countries, occupational factors have
      been implicated in 9 to 15% of all cases of adult asthma. Work-related asthma
      includes (1) immunologic occupational asthma (OA), characterized by a latency
      period before the onset of symptoms; (2) nonimmunologic OA, which occurs after
      single or multiple exposures to high concentrations of irritant materials; (3)
      work-aggravated asthma, which is preexisting or concurrent asthma exacerbated by
      workplace exposures; and (4) variant syndromes. Assessment of the work
      environment has improved, making it possible to measure concentrations of several
      high- and low-molecular-weight agents in the workplace. The identification of
      host factors, polymorphisms, and candidate genes associated with OA is in
      progress and may improve our understanding of mechanisms involved in OA. A
      reliable diagnosis of OA should be confirmed by objective testing early after its
      onset. Removal of the worker from exposure to the causal agent and treatment with
      inhaled glucocorticoids lead to a better outcome. Finally, strategies for
      preventing OA should be implemented and their cost-effectiveness examined.

PMID- 15860755
TI  - Failure of high-dose ergocalciferol to correct vitamin D deficiency in adults
      with cystic fibrosis.
AB  - RATIONALE: Treatment guidelines for vitamin D monitoring and supplementation in
      cystic fibrosis (CF) have recently been developed and published by a consensus
      committee, but have not been prospectively tested. OBJECTIVES: To use these
      guidelines to determine the percentage of adults with CF requiring vitamin D
      repletion therapy and to evaluate the effectiveness of the currently recommended
      high-dose oral ergocalciferol repletion protocol. METHODS: Prospective study of
      clinical outcomes after therapy with the recommended vitamin D repletion
      algorithm. RESULTS: Of 134 adults with CF, 109 (81.3%) were found to have 25
      hydroxyvitamin D (25-OHD) levels below the recommended 30 ng/ml. Sixty-six of
      these adults completed the recommended course of 400,000 IU of oral
      ergocalciferol over 2 months, and only five (8%) responded with correction of
      their serum 25-OHD to the goal of 30 ng/ml or greater (mean change, +0.3 ng/ml;
      from 18.8 to 19.1 ng/ml). In the 33 adults with CF who also completed the
      recommended second course of 800,000 IU of ergocalciferol over 2 months, none
      demonstrated correction of their deficiency (mean change, -1.2 ng/ml).
      CONCLUSION: The results of this study demonstrate that a majority of adults with
      CF have serum 25-OHD levels below 30 ng/ml, and the currently recommended
      ergocalciferol repletion regimen often does not fully correct vitamin D
      deficiency and may need to be revised to include even higher dosing of
      ergocalciferol. Further work is needed to establish the ideal 25-OHD level for
      maximizing calcium absorption and bone health in CF.

PMID- 15860756
TI  - Angiotensin II enhances interleukin-18 mediated inflammatory gene expression in
      vascular smooth muscle cells: a novel cross-talk in the pathogenesis of
      atherosclerosis.
AB  - Vascular smooth muscle cells (VSMCs) express functional interleukin-18 receptors
      (IL-18Rs), composed of alpha and beta subunits. These subunits are elevated in
      VSMCs of atherosclerotic plaques and can be induced by inflammatory agents in
      cultured VSMC. Because both IL-18 and Angiotensin II (Ang II) are implicated in
      atherosclerosis, our objective was to analyze the role of IL-18 signaling and
      potential cross-talk with Ang II in VSMC. We observed that IL-18 activated Src
      kinase, protein kinase C, p38 and JNK MAPKs, Akt kinase, transcription factors NF
      kB and AP-1, and induced expression of pro-inflammatory cytokines in VSMC.
      Pretreatment of VSMC with Ang II enhanced IL-18-induced NF-kB activation and
      cytokine gene expression. Interestingly, Ang II directly increased mRNA and cell
      surface protein levels of the IL-18Ralpha subunit. Functional relevance in an
      organ culture model was demonstrated by the observation that incubation of intact
      mouse aortas ex vivo with Ang II also significantly increased IL-18Ralpha
      expression. Furthermore, Ang II significantly stimulated transcription from a
      minimal IL-18Ralpha promoter containing putative binding sites for STAT and AP-1.
      Ang II also increased in vivo recruitment of STAT-3 on the IL-18Ralpha promoter.
      Finally, dominant negative STAT-3 mutant blocked Ang II-induced IL-18Ralpha
      promoter activation in CHO cells overexpressing AT1a receptor and IL-18Ralpha
      mRNA expression in HVSMC. Thus, Ang II enhances IL-18 induced inflammatory genes
      by increasing IL-18Ralpha expression. These results illustrate a novel mechanism
      wherein Ang II- mediated increases in inflammatory genes and proatherogenic
      effects in the vasculature are enhanced by a vicious loop and cross-talk with the
      IL-18 signaling pathway.

PMID- 15860757
TI  - Cardiac sarcoplasmic reticulum calcium release and load are enhanced by
      subcellular cAMP elevations in PI3Kgamma-deficient mice.
AB  - We recently showed that phosphoinositide-3-kinase-gamma-deficient (PI3Kgamma-/-)
      mice have increased cardiac contractility without changes in heart size compared
      with control mice (ie, PI3Kgamma+/+ or PI3Kgamma+/-). In this study, we show that
      PI3Kgamma-/- cardiomyocytes have elevated Ca2+ transient amplitudes with
      abbreviated decay kinetics compared with control under field-stimulation and
      voltage-clamp conditions. When Ca2+ transients were eliminated with high Ca2+
      buffering, L-type Ca2+ currents (I(Ca,L)), K+ currents, and action potential
      duration (APD) were not different between the groups, whereas, in the presence of
      Ca2+ transients, Ca2+-dependent phase of I(Ca,L) inactivation was abbreviated and
      APD at 90% repolarization was prolonged in PI3Kgamma-/- mice. Excitation
      contraction coupling (ECC) gain, sarcoplasmic reticulum (SR) Ca2+ load, and SR
      Ca(2+) release fluxes measured as Ca2+ spikes, were also increased in PI3Kgamma-/
      cardiomyocytes without detectable changes in Ca2+ spikes kinetics. The cAMP
      inhibitor Rp-cAMP eliminated enhanced ECC and SR Ca2+ load in PI3Kgamma-/-
      without effects in control myocytes. On the other hand, the beta-adrenergic
      receptor agonist isoproterenol increased I(Ca,L) and Ca2+ transient equally by
      approximately 2-fold in both PI3Kgamma-/- and PI3Kgamma+/- cardiomyocytes. Our
      results establish that PI3Kgamma reduces cardiac contractility in a highly
      compartmentalized manner by inhibiting cAMP-mediated SR Ca2+ loading without
      directly affecting other major modulators of ECC, such as AP and I(Ca,L).

PMID- 15860758
TI  - Cardiac overexpression of melusin protects from dilated cardiomyopathy due to
      long-standing pressure overload.
AB  - We have previously shown that genetic ablation of melusin, a muscle specific beta
      1 integrin interacting protein, accelerates left ventricle (LV) dilation and
      heart failure in response to pressure overload. Here we show that melusin
      expression was increased during compensated cardiac hypertrophy in mice subjected
      to 1 week pressure overload, but returned to basal levels in LV that have
      undergone dilation after 12 weeks of pressure overload. To better understand the
      role of melusin in cardiac remodeling, we overexpressed melusin in heart of
      transgenic mice. Echocardiography analysis indicated that melusin over-expression
      induced a mild cardiac hypertrophy in basal conditions (30% increase in
      interventricular septum thickness) with no obvious structural and functional
      alterations. After prolonged pressure overload (12 weeks), melusin overexpressing
      hearts underwent further hypertrophy retaining concentric LV remodeling and full
      contractile function, whereas wild-type LV showed pronounced chamber dilation
      with an impaired contractility. Analysis of signaling pathways indicated that
      melusin overexpression induced increased basal phosphorylation of GSK3beta and
      ERK1/2. Moreover, AKT, GSK3beta and ERK1/2 were hyper-phosphorylated on pressure
      overload in melusin overexpressing compared with wild-type mice. In addition,
      after 12 weeks of pressure overload LV of melusin overexpressing mice showed a
      very low level of cardiomyocyte apoptosis and stromal tissue deposition, as well
      as increased capillary density compared with wild-type. These results demonstrate
      that melusin overexpression allows prolonged concentric compensatory hypertrophy
      and protects against the transition toward cardiac dilation and failure in
      response to long-standing pressure overload.

PMID- 15860759
TI  - Myocardial interstitial matrix metalloproteinase activity is altered by
      mechanical changes in LV load: interaction with the angiotensin type 1 receptor.
AB  - LV myocardial remodeling is a structural hallmark of hypertensive hypertrophy,
      but molecular mechanisms driving this process are not well understood. The matrix
      metalloproteinases (MMPs) can cause myocardial remodeling in chronic disease
      states, but how MMP activity is altered with a mechanical load remains unknown.
      The present study quantified interstitial MMP activity after a discrete increase
      in LV load and dissected out the contributory role of the angiotensin II Type 1
      receptor (AT1R). Pigs (38 kg) were randomized to undergo (1) increased LV load by
      insertion of an intra-aortic balloon pump (IABP) triggered at systole for 3
      hours, then deactivated (n=11); (2) IABP and AT1R blockade (AT1RB; valsartan, 3
      ng/kg/hr; n=6). MMP activity was directly measured in the myocardial interstitium
      using a validated inline digital fluorogenic microdialysis system. IABP
      engagement increased LV peak pressure from 92+/-3 to 113+/-5 and 123+/-7 mm Hg in
      the vehicle and AR1RB group, respectively, and remained elevated throughout the
      IABP period (P<0.05). With IABP disengagement, segmental shortening (% change
      from baseline of 0) remained depressed in the vehicle group (-32.2+/-11.8%,
      P<0.05) but returned to baseline in the AT1RB group (2.3+/-12.5%). MMP activity
      decreased with IABP in both groups. At IABP disengagement, a surge in MMP
      activity occurred in the vehicle group that was abrogated with AT1RB (3.03+/-0.85
      versus 0.07+/-1.55 MMP units/hr, P<0.05). A transient increase in LV load caused
      a cyclic variation in interstitial MMP activity that is regulated in part by the
      AT1R. These temporally dynamic changes in MMP activity likely influence
      myocardial function and structure with increased LV load.

PMID- 15860760
TI  - Understanding conduction system development: a hop, skip and jump away?

PMID- 15860761
TI  - Yin and yang of MCP-1.

PMID- 15860762
TI  - NAD(P)H oxidase-dependent self-propagation of hydrogen peroxide and vascular
      disease.
AB  - Excessive production of reactive oxygen species in the vasculature contributes to
      cardiovascular pathogenesis. Among biologically relevant and abundant reactive
      oxygen species, superoxide (O2*-) and hydrogen peroxide (H2O2) appear most
      important in redox signaling. Whereas O2*- predominantly induces endothelial
      dysfunction by rapidly inactivating nitric oxide (NO*), H2O2 influences different
      aspects of endothelial cell function via complex mechanisms. This review
      discusses recent advances establishing a critical role of H2O2 in the development
      of vascular disease, in particular, atherosclerosis, and mechanisms whereby
      vascular NAD(P)H oxidase-derived H2O2 amplifies its own production. Recent
      studies have shown that H2O2 stimulates reactive oxygen species production via
      enhanced intracellular iron uptake, mitochondrial damage, and sources of vascular
      NAD(P)H oxidases, xanthine oxidase, and uncoupled endothelial nitric oxide
      synthase (eNOS). This self-propagating phenomenon likely prolongs H2O2-dependent
      pathological signaling in vascular cells, thus contributing to vascular disease
      development. The latest progress on Nox functions in vascular cells is also
      discussed [Nox for NAD(P)H oxidases, representing a family of novel NAD(P)H
      oxidases].

PMID- 15860763
TI  - Monetary incentives in support of academic achievement: results of a randomized
      field trial involving high-achieving, low-resource, ethnically diverse urban
      adolescents.
AB  - Significant resources have been directed at understanding and alleviating the
      achievement gap in education. Most programs focused on this aim rely on a top
      down approach, including funding for infrastructure improvement, curriculum
      development, class size, and teacher salaries. This article presents findings
      from a randomized field trial that evaluates a bottom-up approach in which high
      achieving students of diverse racial and ethnic backgrounds from poor families
      are given monetary incentives to maintain their academic standing. The evaluation
      was designed to explore the role of monetary incentives as a mechanism for
      promoting resiliency in the face of poverty-related challenge. Discussion of what
      motivates students to learn is framed as a function of normal cognitive and
      socioemotional development in challenging environments. Evaluation findings
      indicate that monetary incentives are effective in promoting academic success to
      different degrees and for different reasons depending on students' perception of
      the meaning of the incentive in relation to their emergent identity.

PMID- 15860764
TI  - The effect of economic stability on family stability among welfare recipients.
AB  - The main rationale for defining two-parent families eligible for welfare was to
      keep families intact by eliminating an incentive for union dissolution. But there
      are other reasons for family instability, most notably women's reduced economic
      gain from marriage associated with having a chronically unemployed husband. This
      article explores the hypothesis that husband's unemployment increases union
      dissolution among welfare recipients. The analysis uses data from California's
      Link-Up demonstration project. A discrete-time event-history methodology was
      employed to examine family instability. The findings show that husband's
      unemployment and the family's long-term welfare dependency lead to breakup, net
      of race, age, and number of children.

PMID- 15860765
TI  - Increasing the degrees of freedom in existing group randomized trials: the df*
      approach.
AB  - This study describes a method for incorporating external estimates of intraclass
      correlation to improve the precision for the analysis of an existing group
      randomized trial. The authors use a random-effects meta-analytic approach to pool
      the information across studies, which takes into account any interstudy
      heterogeneity that may exist. This approach can be used in several different
      situations to estimate the degrees of freedom available for an adjusted test of
      the intervention effect in a study where the challenges of group-randomized
      trials were not fully considered when the study was planned. The authors discuss
      the limitations of this approach and the circumstances in which it is likely to
      be helpful.

PMID- 15860766
TI  - Increasing the degrees of freedom in future group randomized trials: the df*
      approach.
AB  - This article builds on the previous article by Blitstein et al. (2005), which
      showed how external estimates of intraclass correlation can be used to improve
      the precision for the analysis of an existing group randomized trial. The authors
      extend that work to sample size estimation and power analysis for future group
      randomized trials. Often this approach will allow a smaller study than would
      otherwise be possible without sacrificing statistical power. Such studies are
      needed, for example, as pilot studies to help plan for a full-scale efficacy
      trial, as replication studies, or in situations in which resource constraints
      prohibit a larger trial. The authors discuss the circumstances under which this
      strategy will be most helpful and the risks associated with conducting smaller
      studies.

PMID- 15860767
TI  - Diagnostic application of padlock probes--multiplex detection of plant pathogens
      using universal microarrays.
AB  - Padlock probes (PLPs) are long oligonucleotides, whose ends are complementary to
      adjacent target sequences. Upon hybridization to the target, the two ends are
      brought into contact, allowing PLP circularization by ligation. PLPs provide
      extremely specific target recognition, which is followed by universal
      amplification and microarray detection. Since target recognition is separated
      from downstream processing, PLPs enable the development of flexible and
      extendable diagnostic systems, targeting diverse organisms. To adapt padlock
      technology for diagnostic purposes, we optimized PLP design to ensure high
      specificity and eliminating ligation on non-target sequences under real-world
      assay conditions. We designed and tested 11 PLPs to target various plant
      pathogens at the genus, species and subspecies levels, and developed a prototype
      PLP-based plant health chip. Excellent specificity was demonstrated toward the
      target organisms. Assay background was determined for each hybridization using a
      no-target reference sample, which provided reliable and sensitive identification
      of positive samples. A sensitivity of 5 pg genomic DNA and a dynamic range of
      detection of 100 were observed. The developed multiplex diagnostic system was
      validated using genomic DNAs of characterized isolates and artificial mixtures
      thereof. The demonstrated system is adaptable to a wide variety of applications
      ranging from pest management to environmental microbiology.

PMID- 15860768
TI  - Multiplex amplification enabled by selective circularization of large sets of
      genomic DNA fragments.
AB  - We present a method to specifically select large sets of DNA sequences for
      parallel amplification by PCR using target-specific oligonucleotide constructs,
      so-called selectors. The selectors are oligonucleotide duplexes with single
      stranded target-complementary end-sequences that are linked by a general sequence
      motif. In the selection process, a pool of selectors is combined with denatured
      restriction digested DNA. Each selector hybridizes to its respective target,
      forming individual circular complexes that are covalently closed by enzymatic
      ligation. Non-circularized fragments are removed by exonucleolysis, enriching for
      the selected fragments. The general sequence that is introduced into the
      circularized fragments allows them to be amplified in parallel using a universal
      primer pair. The procedure avoids amplification artifacts associated with
      conventional multiplex PCR where two primers are used for each target, thereby
      reducing the number of amplification reactions needed for investigating large
      sets of DNA sequences. We demonstrate the specificity, reproducibility and
      flexibility of this process by performing a 96-plex amplification of an arbitrary
      set of specific DNA sequences, followed by hybridization to a cDNA microarray.
      Eighty-nine percent of the selectors generated PCR products that hybridized to
      the expected positions on the array, while little or no amplification artifacts
      were observed.

PMID- 15860769
TI  - PieceMaker: selection of DNA fragments for selector-guided multiplex
      amplification.
AB  - We describe PieceMaker, a software tool for the design of applications of
      selector probes-oligonucleotide probes that direct circularization of target
      nucleic acid molecules. Such probes can be combined in parallel to circularize a
      selection of fragments from restriction digested total genomic DNA. These
      fragments can then be amplified in a single PCR using a common primer pair,
      yielding substrates for subsequent analyses, such as parallel genotyping or
      sequencing. However, designing multiplex selector assays is a laborious task. The
      PieceMaker program alleviates this problem by selecting restriction enzymes to
      generate suitable fragments for selection, and generating the output data
      required to design the selector probes.

PMID- 15860770
TI  - Array-based analysis of genomic DNA methylation patterns of the tumour suppressor
      gene p16INK4A promoter in colon carcinoma cell lines.
AB  - Aberrant DNA methylation at CpG dinucleotides can result in epigenetic silencing
      of tumour suppressor genes and represents one of the earliest events in
      tumourigenesis. To date, however, high-throughput tools that are capable of
      surveying the methylation status of multiple gene promoters have been restricted
      to a limited number of cytosines. Here, we present an oligonucleotide microarray
      that permits the parallel analysis of the methylation status of individual
      cytosines, thus combining high throughput and high resolution. The approach was
      used to study the CpG island in the promoter region of the tumour suppressor gene
      p16(INK4A). In total, 876 oligonucleotide probes of 21 nt in length were used to
      inspect the methylation status of 53 CpG dinucleotides, producing correct signals
      in colorectal cancer cell lines as well as control samples with a defined
      methylation status. The information was validated by established alternative
      methods. The overall methylation pattern was consistent for each cell line, while
      different between them. At the level of individual cytosines, however,
      significant variations between individual cells of the same type were found, but
      also consistencies across the panel of cancer cell lines were observed.

PMID- 15860771
TI  - Suppression of vascular endothelial growth factor expression at the
      transcriptional and post-transcriptional levels.
AB  - Gene expression is regulated at the transcriptional and post-transcriptional
      levels. Therefore, in order to achieve a high level of silencing, which includes
      minimizing any residual expression of a target gene, suppression at both the
      transcriptional and post-transcriptional levels is required. In this study, we
      describe a new method for highly efficient gene silencing that combines zinc
      finger protein-mediated transcriptional repression and small interfering RNA
      (siRNA)-mediated inhibition of post-transcriptional events. To measure the amount
      of gene expression under various conditions, we used a luciferase reporter gene
      that was driven by a variety of promoters, including that of the human vascular
      endothelial growth factor-A (VEGF-A) gene. We also measured expression of the
      endogenous VEGF-A gene. Inhibition of gene expression by each of the two
      individual technologies was effective, but in-depth analyses revealed residual
      expression of the target gene. The combination of specific zinc finger
      transcription factors and siRNAs greatly enhanced the silencing of the human VEGF
      A gene, not only when cells were grown in the presence of normal amounts of
      oxygen but also under conditions of hypoxic stimulation. These results suggest
      that a bi-level approach to the silencing of VEGF-A expression may be clinically
      beneficial as part of a cancer treatment protocol.

PMID- 15860772
TI  - Large-scale analysis of human alternative protein isoforms: pattern
      classification and correlation with subcellular localization signals.
AB  - We investigated human alternative protein isoforms of >2600 genes based on full
      length cDNA clones and SwissProt. We classified the isoforms and examined their
      co-occurrence for each gene. Further, we investigated potential relationships
      between these changes and differential subcellular localization. The two most
      abundant patterns were the one with different C-terminal regions and the one with
      an internal insertion, which together account for 43% of the total. Although
      changes of the N-terminal region are less common than those of the C-terminal
      region, extension of the C-terminal region is much less common than that of the N
      terminal region, probably because of the difficulty of removing stop codons in
      one isoform. We also found that there are some frequently used combinations of co
      occurrence in alternative isoforms. We interpret this as evidence that there is
      some structural relationship which produces a repertoire of isoformal patterns.
      Finally, many terminal changes are predicted to cause differential subcellular
      localization, especially in targeting either peroxisomes or mitochondria. Our
      study sheds new light on the enrichment of the human proteome through alternative
      splicing and related events. Our database of alternative protein isoforms is
      available through the internet.

PMID- 15860773
TI  - Characterization of the DNA-binding domain and identification of the active site
      residue in the 'Gyr A' half of Leishmania donovani topoisomerase II.
AB  - DNA topoisomerase II is a multidomain homodimeric enzyme that changes DNA
      topology by coupling ATP hydrolysis to the transport of one DNA helix through a
      transient double-stranded break in another. To investigate the biochemical
      properties of the individual domains of Leishmania donovani topoisomerase II,
      four truncation mutants were generated. Deletion of 178 aminoacids from the C
      terminus (core and LdDeltaC1058) had no apparent effect on the DNA-binding or
      cleavage activities of the enzymes. However, when 429 aminoacids from the N
      terminus and 451 aminoacids from the C-terminus were removed (LdDeltaNDeltaC),
      the enzyme was no longer active. Moreover, the removal of 429 aminoacids from the
      N-terminus (LdDeltaNDeltaC, core and LdDeltaN429) render the mutant proteins
      incapable of performing ATP hydrolysis. The mutant proteins show cleavage
      activities at wide range of KCl concentrations (25-350 mM). In addition, the
      mutant proteins, excepting LdDeltaNDeltaC, can also act on kDNA and linearize the
      minicircles. Surprisingly, the mutant proteins fail to show the formation of the
      enhanced cleavable complex in the presence of etoposide. Our findings suggest
      that the conformation required for interaction with the drug is absent in the
      mutant proteins. Here, we have also identified Tyr(775) through direct sequencing
      of the DNA linked peptide as the catalytic residue implicated in DNA-breakage and
      rejoining. Taken together, our results demonstrate that topoisomerase II are
      functionally and mechanistically conserved enzymes and the variations in activity
      seem to reflect functional optimization for its physiological role during
      parasite genome replication.

PMID- 15860774
TI  - Transcribed processed pseudogenes in the human genome: an intermediate form of
      expressed retrosequence lacking protein-coding ability.
AB  - Pseudogenes, in the case of protein-coding genes, are gene copies that have lost
      the ability to code for a protein; they are typically identified through
      annotation of disabled, decayed or incomplete protein-coding sequences. Processed
      pseudogenes (PPsigs) are made through mRNA retrotransposition. There is
      overwhelming genomic evidence for thousands of human PPsigs and also dozens of
      human processed genes that comprise complete retrotransposed copies of other
      genes. Here, we survey for an intermediate entity, the transcribed processed
      pseudogene (TPPsig), which is disabled but nonetheless transcribed. TPPsigs may
      affect expression of paralogous genes, as observed in the case of the mouse
      makorin1-p1 TPPsig. To elucidate their role, we identified human TPPsigs by
      mapping expressed sequences onto PPsigs and, reciprocally, extracting TPPsigs
      from known mRNAs. We consider only those PPsigs that are homologous to either non
      mammalian eukaryotic proteins or protein domains of known structure, and require
      detection of identical coding-sequence disablements in both the expressed and
      genomic sequences. Oligonucleotide microarray data provide further expression
      verification. Overall, we find 166-233 TPPsigs ( approximately 4-6% of PPsigs).
      Proteins/transcripts with the highest numbers of homologous TPPsigs generally
      have many homologous PPsigs and are abundantly expressed. TPPsigs are
      significantly over-represented near both the 5' and 3' ends of genes; this
      suggests that TPPsigs can be formed through gene-promoter co-option, or intrusion
      into untranslated regions. However, roughly half of the TPPsigs are located away
      from genes in the intergenic DNA and thus may be co-opting cryptic promoters of
      undesignated origin. Furthermore, TPPsigs are unlike other PPsigs and processed
      genes in the following ways: (i) they do not show a significant tendency to
      either deposit on or originate from the X chromosome; (ii) only 5% of human
      TPPsigs have potential orthologs in mouse. This latter finding indicates that the
      vast majority of TPPsigs is lineage specific. This is likely linked to well
      documented extensive lineage-specific SINE/LINE activity. The list of TPPsigs is
      available at: http://www.biology.mcgill.ca/faculty/harrison/tppg/bppg.tov (or)
      http:pseudogene.org.

PMID- 15860775
TI  - Independent binding sites of small protein B onto transfer-messenger RNA during
      trans-translation.
AB  - Stalled bacterial ribosomes are freed by transfer-messenger RNA (tmRNA). With the
      help of small protein B (SmpB), protein synthesis restarts and tmRNA adds a tag
      to the stalled protein for destruction. The conformation of a 347 nt long tmRNA
      from a thermophile and its interactions with SmpB were monitored using structural
      probes. The RNA is highly folded, including the reading frame, with <30% of
      unpaired residues. Footprints between SmpB and tmRNA are in the elbow of the tRNA
      domain, in some pseudoknots including one essential for function and in the lower
      part of the stem exiting the tRNA domain. The footprints outside the tRNA domain
      are scattered onto the tmRNA sequence, but form a cluster onto its tertiary
      structure derived from cryo-EM data. Some footprints flank the first triplet to
      be translated in tmRNA, suggesting that SmpB participates in the insertion of the
      tmRNA-encoded reading frame into the decoding center. To discriminate between a
      conformational rearrangement of tmRNA and independent binding sites, surface
      plasmon resonance was used and has identified three independent binding sites of
      SmpB on the RNA, including the site on the tRNA domain. Accordingly, SmpB is
      proposed to move on the tmRNA scaffold during trans-translation.

PMID- 15860776
TI  - Recurrent structural RNA motifs, Isostericity Matrices and sequence alignments.
AB  - The occurrences of two recurrent motifs in ribosomal RNA sequences, the Kink-turn
      and the C-loop, are examined in crystal structures and systematically compared
      with sequence alignments of rRNAs from the three kingdoms of life in order to
      identify the range of the structural and sequence variations. Isostericity
      Matrices are used to analyze structurally the sequence variations of the
      characteristic non-Watson-Crick base pairs for each motif. We show that
      Isostericity Matrices for non-Watson-Crick base pairs provide important tools for
      deriving the sequence signatures of recurrent motifs, for scoring and refining
      sequence alignments, and for determining whether motifs are conserved throughout
      evolution. The systematic use of Isostericity Matrices identifies the positions
      of the insertion or deletion of one or more nucleotides relative to the
      structurally characterized examples of motifs and, most importantly, specifies
      whether these changes result in new motifs. Thus, comparative analysis coupled
      with Isostericity Matrices allows one to produce and refine structural sequence
      alignments. The analysis, based on both sequence and structure, permits therefore
      the evaluation of the conservation of motifs across phylogeny and the derivation
      of rules of equivalence between structural motifs. The conservations observed in
      Isostericity Matrices form a predictive basis for identifying motifs in
      sequences.

PMID- 15860777
TI  - The requirement of yeast replication origins for pre-replication complex proteins
      is modulated by transcription.
AB  - The mini-chromosome maintenance proteins Mcm2-7 are essential for DNA
      replication. They are loaded onto replication origins during G1 phase of the cell
      cycle to form a pre-replication complex (pre-RC) that licenses each origin for
      subsequent initiation. We have investigated the DNA elements that determine the
      dependence of yeast replication origins on Mcm2-7 activity, i.e. the sensitivity
      of an origin to mcm mutations. Using chimaeric constructs from mcm sensitive and
      mcm insensitive origins, we have identified two main elements affecting the
      requirement for Mcm2-7 function. First, transcription into an origin increases
      its dependence on Mcm2-7 function, revealing a conflict between pre-RC assembly
      and transcription. Second, sequence elements within the minimal origin influence
      its mcm sensitivity. Replication origins show similar differences in sensitivity
      to mutations in other pre-RC proteins (such as Origin Recognition Complex and
      Cdc6), but not to mutations in initiation and elongation factors, demonstrating
      that the mcm sensitivity of an origin is determined by its ability to establish a
      pre-RC. We propose that there is a hierarchy of replication origins with respect
      to the range of pre-RC protein concentrations under which they will function.
      This hierarchy is both 'hard-wired' by the minimal origin sequences and 'soft
      wired' by local transcriptional context.

PMID- 15860778
TI  - Dissecting eukaryotic translation and its control by ribosome density mapping.
AB  - Translation of an mRNA is generally divided into three stages: initiation,
      elongation and termination. The relative rates of these steps determine both the
      number and position of ribosomes along the mRNA, but traditional velocity
      sedimentation assays for the translational status of mRNA determine only the
      number of bound ribosomes. We developed a procedure, termed Ribosome Density
      Mapping (RDM), that uses site-specific cleavage of polysomal mRNA followed by
      separation on a sucrose gradient and northern analysis, to determine the number
      of ribosomes associated with specified portions of a particular mRNA. This
      procedure allows us to test models for translation and its control, and to
      examine properties of individual steps of translation in vivo. We tested specific
      predictions from the current model for translational control of GCN4 expression
      in yeast and found that ribosomes were differentially associated with the uORFs
      elements and coding region under different growth conditions, consistent with
      this model. We also mapped ribosome density along the ORF of several mRNAs, to
      probe basic kinetic properties of translational steps in yeast. We found no
      detectable decline in ribosome density between the 5' and 3' ends of the ORFs,
      suggesting that the average processivity of elongation is very high. Conversely,
      there was no queue of ribosomes at the termination site, suggesting that
      termination is not very slow relative to elongation and initiation. Finally, the
      RDM results suggest that less frequent initiation of translation on mRNAs with
      longer ORFs is responsible for the inverse correlation between ORF length and
      ribosomal density that we observed in a global analysis of translation. These
      results provide new insights into eukaryotic translation in vivo.

PMID- 15860779
TI  - A benchmark of multiple sequence alignment programs upon structural RNAs.
AB  - To date, few attempts have been made to benchmark the alignment algorithms upon
      nucleic acid sequences. Frequently, sophisticated PAM or BLOSUM like models are
      used to align proteins, yet equivalents are not considered for nucleic acids;
      instead, rather ad hoc models are generally favoured. Here, we systematically
      test the performance of existing alignment algorithms on structural RNAs. This
      work was aimed at achieving the following goals: (i) to determine conditions
      where it is appropriate to apply common sequence alignment methods to the
      structural RNA alignment problem. This indicates where and when researchers
      should consider augmenting the alignment process with auxiliary information, such
      as secondary structure and (ii) to determine which sequence alignment algorithms
      perform well under the broadest range of conditions. We find that sequence
      alignment alone, using the current algorithms, is generally inappropriate <50-60%
      sequence identity. Second, we note that the probabilistic method ProAlign and the
      aging Clustal algorithms generally outperform other sequence-based algorithms,
      under the broadest range of applications.

PMID- 15860780
TI  - General lifestyle activities as a predictor of current cognition and cognitive
      change in older adults: a cross-sectional and longitudinal examination.
AB  - General lifestyle activities were examined as a predictor of current cognition
      and cognitive change over a 6-year interval in older adults. Participants were
      drawn from a population-based longitudinal study, and they completed the Adelaide
      Activities Profile and a battery of tests measuring cognition and sensory
      functioning. Hierarchical regression analyses revealed that, after sensory
      functioning was controlled for, activity was a significant predictor of current
      levels of speed, picture naming, incidental recall, and verbal fluency, and of
      cognitive change in speed, picture naming, and incidental recall. Commonality
      analyses demonstrated that activity accounted for a notable amount of the total
      variance in cognition, and that there was prominent overlap in shared variance
      between activity and age, and between sensory functioning and age. These findings
      suggest that engaging in general lifestyle activities may help to promote
      successful cognitive aging.

PMID- 15860781
TI  - Do we get better at picking our battles? Age group differences in descriptions of
      behavioral reactions to interpersonal tensions.
AB  - Individuals of various ages may react in different ways when they are upset with
      their social partners. This study examines age group differences in descriptions
      of behavioral reactions to interpersonal tensions. Participants ages 13 to 99 (84
      men, 100 women) described interpersonal tensions that occurred with close and
      problematic social network members. Descriptions were coded with Rusbult's
      typology of conflict strategies (voice, loyalty, neglect, exit). Multilevel
      models revealed that older adults were more likely to report loyalty strategies
      (e.g., doing nothing) while younger people were more likely to report exit (e.g.,
      yelling) strategies in response to interpersonal problems. These age differences
      were not accounted for by intensity of distress, relationship quality, contact
      frequency, or type of social partner. It appears that individuals are better able
      to regulate their behavioral responses to interpersonal problems as they age.

PMID- 15860782
TI  - Effects of Alzheimer's disease on visual enumeration.
AB  - Speeded enumeration of visual objects typically produces fast and accurate
      performance for up to 3 to 4 items (subitization) but slower and less accurate
      performance thereafter (counting). We investigated enumeration ability in
      patients with Alzheimer's disease (AD) and in age-matched controls. AD patients
      were slower overall than controls. The subitizing span was significantly reduced
      in AD patients compared with controls (2.3 vs 3.5 items) and counting rate was
      significantly slower (451 vs 349 ms/item). Error rates were similar in the two
      groups except at numerosity 3, when AD patients made errors but controls did not
      (consistent with their subitizing spans). Within the AD patient group, several
      aspects of performance correlated significantly with Mini-Mental State
      Examination scores. Together, the results provide a striking contrast with
      studies showing preservation of enumeration ability in normal aging.

PMID- 15860783
TI  - Black-white differences in depressive symptoms among older adults over time.
AB  - This study examines racial differences in depressive symptoms among older adults
      over time. The subjects were 4,275 community-dwelling persons aged 65 and older
      (62% Black) who participated in the Chicago Health and Aging Project (CHAP)
      during a period of 9 years. Depression was measured using a summary score of the
      10-item Center for Epidemiologic Studies-Depression scale (CES-D). We modeled
      depressive symptoms using the method of General Estimating Equations and a
      Poisson error structure. We found a significant race effect at baseline with
      Blacks reporting approximately 60% more symptoms than Whites (beta = 0.467 on the
      log scale, p < .001). The differences were larger for men than for women. After
      controlling for age, sex, time, education, income, and related interaction terms,
      the baseline race effect was reduced by almost half (beta = 0.225, p < .001) but
      remained robust. The racial differences increased slightly over time. Our
      findings support heightened awareness of depression in older Black populations.

PMID- 15860784
TI  - Altruism relates to health in an ethnically diverse sample of older adults.
AB  - The existing literature indicates links between aspects of social network
      functioning and health outcomes. It is generally believed that networks that are
      larger or provide greater instrumental and emotional support contribute to
      improved health and, perhaps, greater longevity. Recently, it has been suggested
      that giving as well as receiving social support may be of benefit. On the basis
      of evolutionary theories of emotion and altruism, the current study sought to
      test this thesis in a large, ethnically diverse sample of community-dwelling
      older adults. As expected, levels of social support given were associated with
      lower morbidity, whereas levels of receiving were not. It is important that these
      relations held even when (a) socioeconomic status, education, marital status,
      age, gender, ethnicity, and (b) absolute network size and activity limitation
      were controlled for. Results are discussed in terms of their implications for
      theory regarding the relations among social exchanges, giving, and later life
      adaptation among older adults.

PMID- 15860785
TI  - Self-discipline and self-consciousness predict subjective memory in older adults.
AB  - Research has shown the personality variables of conscientiousness and neuroticism
      to be related to subjective memory in older adults. This study was designed to
      determine the specific facets of these traits involved in the relation between
      personality and memory complaints. Subjective memory evaluations were examined in
      85 community-dwelling people aged 56 to 94 years. Regression analysis revealed
      that one facet of conscientiousness (self-discipline) and two facets of
      neuroticism (self-consciousness and anxiety) explained almost one third of the
      variance in subjective memory complaints. Anxiety acted as a suppressor variable
      to enhance the contribution of self-consciousness. Objective measures of episodic
      and prospective memory were not related to subjective memory. Effective
      treatments of memory complaints in healthy older adults may have to focus on
      enhancing self-discipline and self-concept.

PMID- 15860786
TI  - Motor control in old age: evidence of impaired low-level inhibition.
AB  - In the masked prime task, responses to supraliminal targets are influenced by
      previously presented subliminal primes. When targets follow primes immediately,
      positive compatibility effects are obtained such that performance is better when
      prime and target are compatible (mapped to the same response) than when they are
      incompatible (mapped to opposite responses). In young adults, this pattern
      reverses with longer interstimulus intervals (negative compatibility effect).
      These effects reflect an activation-followed-by-inhibition process: Primes
      trigger an initial activation of their corresponding motor response, which is
      subsequently inhibited. The present study demonstrates that healthy older adults
      (M = 76 years) show a substantial positive compatibility effect with a short
      prime-target interval, but they fail to produce reliable negative compatibility
      effects with longer intervals, indicating an age-related impairment in low-level
      motor control.

PMID- 15860788
TI  - Beyond appearances: perspectives on identity in later life and some implications
      for method.
AB  - Two areas of controversy are examined in this article, arising from contemporary
      debate on identity in later life. The first centers on whether adults are
      essentially similar regardless of age or whether different stages of life confer
      different life priorities. The second addresses the management of self in later
      life, with special attention being given to alternative interpretations of the
      relationship between interior and exterior experience. An increasing awareness of
      diversity in life-course patterns suggests that issues concerning uniformity,
      distinctiveness, and the uses of masquerade in intergenerational contexts should
      be revisited. Here, the influence of simple and complex states of mind is
      examined as a factor in intergenerational power, and the expression of agency in
      later life is discussed. These issues not only propel us forward in our
      understanding of gerontological phenomena, they also point to potential sources
      of research bias associated with specifically intergenerational contexts.
      Finally, suggestions are made with respect to research training.

PMID- 15860789
TI  - Age identity and subjective well-being: a comparison of the United States and
      Germany.
AB  - OBJECTIVE: This article investigates the theoretical and empirical relationship
      between age identity and subjective well-being (SWB) in a cross-national context.
      Feeling younger than one's actual age is considered a self-enhancing illusion
      that contributes to SWB even beyond factors predicting age identities and SWB,
      such as health and socioeconomic status. As the United States is more youth
      oriented than Germany, age identities are expected to be more adaptive for
      American adults. METHODS: Data are from respondents between 40 and 74 years of
      age who participated in the National Survey of Midlife Development in the United
      States (N = 2,006) or the German Aging Survey (N = 3,331). RESULT: Analyses using
      the pooled sample reveal that feeling younger than one's actual age is related to
      higher levels of life satisfaction and positive affect and to lower levels of
      negative affect, even when controlling for sociodemographic variables. Country
      specific analyses indicate that the relationship between age identity and
      negative affect holds only for the United States. DISCUSSION: Age identities play
      a role in more varied aspects of psychosocial adaptation in the United States
      than in Germany. It is concluded that the cultural context needs to be included
      more explicitly in gerontological theories and research.

PMID- 15860790
TI  - Racial differences in formal long-term care: does the timing of parenthood play a
      role?
AB  - OBJECTIVE: This article examines the association between race and the timing of
      formal long-term care (LTC) service use, both institutional and community based.
      It seeks to understand whether early parenthood predicts the timing of LTC use
      later in life and whether it in turn mediates the association between race and
      LTC use. In particular, it explores whether the lower rate of formal LTC use
      among African Americans is due in some part to the earlier inception of
      parenthood. METHODS: Linking measures from the 1989 National Long-Term Care
      Survey with Medicare claims (1989-1993), we model age at first use of
      institutional (skilled nursing facility) care and home health as competing risks
      using a Cox proportional hazards model. RESULT: Early parenthood accelerates
      first use of home health for Whites but delays first use for Blacks. The
      likelihood of any LTC use by race group converges as timing of parenthood
      increases. DISCUSSION: Differential effects of teen childbearing across race
      groups indicate differential vulnerability to LTC needs among early parents.

PMID- 15860791
TI  - Further evidence for the importance of subclinical functional limitation and
      subclinical disability assessment in gerontology and geriatrics.
AB  - OBJECTIVE: The objectives of this work were to determine the prevalence of self
      reported subclinical status for functional limitation and disability at baseline
      and assess their independent effects on the onset of functional limitation and
      disability 1-2 years later. METHODS: Nine hundred ninety-eight African American
      men and women 49-65 years old in St. Louis, MO, received comprehensive in-home
      evaluations at baseline and two annual telephone follow-ups. Outcome measures
      included walking a half-mile, climbing steps, stooping-crouching-kneeling,
      lifting or carrying 10 lbs., and doing heavy housework. RESULT: The baseline
      prevalence of subclinical status was 26.4% for walking a half-mile, 26.8% for
      climbing steps, 39.0% for stooping-crouching-kneeling, 29.1% for lifting or
      carrying 10 lbs., and 22.7% for doing heavy housework. The adjusted odds ratios
      for the task-specific subclinical status measure at baseline on developing
      difficulty 1-2 years later were 1.68 (p < .05) for walking a half-mile, 4.46 (p <
      .001) for climbing steps, 2.48 (p < .001) for stooping-crouching-kneeling, 2.51
      (p < .001) for lifting or carrying 10 lbs., and 2.22 (p < .001) for doing heavy
      housework. Performance tests (tandem stand, chair stands, and preferred gait
      speed) did not have consistent independent effects on the onset of functional
      limitation or disability. CONCLUSION: The subclinical status measures were the
      main predictors of the onset of difficulty in all tasks and functions 1-2 years
      later. Interventions to reduce frailty should focus on self-reported subclinical
      status as an early warning system.

PMID- 15860792
TI  - The causes of homelessness in later life: findings from a 3-nation study.
AB  - OBJECTIVE: This article presents findings from a study of the causes of
      homelessness among newly homeless older people in selected urban areas of the
      United States, England, and Australia. METHODS: Interviews were conducted in each
      country with > or =122 older people who had become homeless during the last 2
      years. Information was also collected from the subjects' key workers about the
      circumstances and problems that contributed to homelessness. RESULT: Two-thirds
      of the subjects had never been homeless before. Antecedent causes were the
      accommodation was sold or needed repair, rent arrears, death of a close relative,
      relationship breakdown, and disputes with other tenants and neighbors.
      Contributory factors were physical and mental health problems, alcohol abuse, and
      gambling problems. DISCUSSION: Most subjects became homeless through a
      combination of personal problems and incapacities, welfare policy gaps, and
      service delivery deficiencies. Whereas there are nation-specific variations,
      across the three countries, the principal causes and their interactions are
      similar.

PMID- 15860793
TI  - Widow(er) poverty and out-of-pocket medical expenditures near the end of life.
AB  - OBJECTIVES: Elderly widows are three times as likely to live in poverty as older
      married people. This study investigates the gap in poverty, income, and wealth
      between these groups. Focus is placed on the role played by out-of-pocket medical
      expenditures spent on dying spouses. METHODS: A national panel survey of people
      age 70 and older in 1993 was used. Income, poverty, wealth, and out-of-pocket
      expenditures were examined before and after widowhood, with comparisons made with
      couples not experiencing a death. RESULTS: Forty-four percent of the difference
      in economic status between widow(er)s and married elderly persons was due to
      disparities in economic status that existed prior to widowhood. The remaining 56%
      was due to factors more directly related to the death of a spouse, including the
      loss of income and expenses associated with dying. On average, out-of-pocket
      medical expenditures in the final 2 years of life were equal to 30% of the
      couple's annual income. For couples in the bottom quarter of the income
      distribution, these expenditures were 70% of their income. DISCUSSION: As policy
      makers continue to debate expansions and reforms of Medicare, the potential
      effects of these reforms on economic well-being, particularly among widows,
      should be considered.

PMID- 15860794
TI  - Diverse effects of eosinophil cationic granule proteins on IMR-32 nerve cell
      signaling and survival.
AB  - Activated eosinophils release potentially toxic cationic granular proteins,
      including the major basic proteins (MBP) and eosinophil-derived neurotoxin (EDN).
      However, in inflammatory conditions including asthma and inflammatory bowel
      disease, localization of eosinophils to nerves is associated with nerve
      plasticity, specifically remodeling. In previous in vitro studies, we have shown
      that eosinophil adhesion to IMR-32 nerve cells, via nerve cell intercellular
      adhesion molecule-1, results in an adhesion-dependent release of granule
      proteins. We hypothesized that released eosinophil granule proteins may affect
      nerve cell signaling and survival, leading to nerve cell remodeling. Culture in
      serum-deprived media induced apoptosis in IMR-32 cells that was dose-dependently
      abolished by inclusion of MBP1 but not by EDN. Both MBP1 and EDN induced
      phosphorylation of Akt, but with divergent time courses and intensities, and
      survival was independent of Akt. MBP1 induced activation of neural nuclear factor
      (NF)-kappaB, from 10 min to 12 h, declining by 24 h, whereas EDN induced a short
      lived activation of NF-kappaB. MBP1-induced protection was dependent on
      phosphorylation of ERK 1/2 and was related to a phospho-ERK-dependent
      upregulation of the NF-kappaB-activated anti-apoptotic gene, Bfl-1. This
      signaling pathway was not activated by EDN. Thus, MBP1 released from eosinophils
      at inflammatory sites may regulate peripheral nerve plasticity by inhibiting
      apoptosis.

PMID- 15860795
TI  - Interleukin-25-induced chemokines and interleukin-6 release from eosinophils is
      mediated by p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and
      nuclear factor-kappaB.
AB  - Interleukin (IL)-25, a novel Th2 cytokine, is capable of amplifying allergic
      inflammation. We investigated the modulation of nuclear factor (NF)-kappaB and
      mitogen-activated protein kinases (MAPK) pathways in IL-25-activated eosinophils,
      the principal effector cells of allergic inflammation, for the in vitro release
      of chemokines including monocyte chemoattractant protein-1 (MCP-1), IL-8, and
      macrophage inflammatory protein (MIP)-1alpha, and inflammatory cytokine IL-6.
      Gene expression of chemokines and IL-6 was evaluated by RT-PCR, and
      concentrations of chemokines and cytokine were measured by cytokine protein
      array, cytometric bead array, and enzyme-linked immunosorbent assay. NF-kappaB, c
      Jun amino-terminal kinase (JNK), and p38 MAPK activities in eosinophils were
      assessed by electrophoretic mobility shift assay and Western blot. IL-25 was
      found to upregulate the gene expression of chemokines MCP-1, MIP-1alpha, and IL
      8, and cytokine IL-6, in eosinophils, and to significantly increase the release
      of the above chemokines and IL-6 from eosinophils. IL-25 could also activate the
      JNK, p38 MAPK, and NF-kappaB activities of eosinophils, while inhibitor of
      IkappaB-alpha phosphorylation (BAY11-7082), JNK (SP600125), and p38 MAPK
      (SB203580) could suppress the release of IL-8, MIP-1alpha, MCP-1, and IL-6.
      Together, the above results showed that the induction of MCP-1, MIP-1alpha, IL-8,
      and IL-6 in IL-25-activated eosinophils are regulated by JNK, p38 MAPK, and NF
      kappaB pathways.

PMID- 15860796
TI  - Lung surfactant gelation induced by epithelial cells exposed to air pollution or
      oxidative stress.
AB  - Lung surfactant lowers surface tension and adjusts interfacial rheology to
      facilitate breathing. A novel instrument, the interfacial stress rheometer (ISR),
      uses an oscillating magnetic needle to measure the shear viscosity and elasticity
      of a surfactant monolayer at the air-water interface. The ISR reveals that calf
      lung surfactant, Infasurf, exhibits remarkable fluidity, even when exposed to air
      pollution residual oil fly ash (ROFA), hydrogen peroxide (H2O2), or conditioned
      media from resting A549 alveolar epithelial cells (AEC). However, when Infasurf
      is exposed to a subphase of the soluble fraction of ROFA- or H2O2-treated AEC
      conditioned media, there is a prominent increase in surfactant elasticity and
      viscosity, representing two-dimensional gelation. Surfactant gelation is
      decreased when ROFA-AEC are pretreated with inhibitors of cellular reactive
      oxygen species (ROS), or with a mitochondrial anion channel inhibitor, as well as
      when A549-rho0 cells that lack mitochondrial DNA and functional electron
      transport are investigated. These results implicate both mitochondrial and
      nonmitochondrial ROS generation in ROFA-AEC-induced surfactant gelation. A549
      cells treated with H2O2 demonstrate a dose-dependent increase in lung surfactant
      gelation. The ISR is a unique and sensitive instrument to characterize surfactant
      gelation induced by oxidatively stressed AEC.

PMID- 15860797
TI  - Expression and regulation of CC class chemokines in the dystrophic (mdx)
      diaphragm.
AB  - In the murine (mdx) model of Duchenne muscular dystrophy, dystrophic changes are
      much more severe in the diaphragm than in limb muscles, and the diaphragm more
      closely resembles the human disease phenotype. Chemokines could play a central
      role in governing such phenotypic differences, as inflammation is an important
      disease modifier. Here we report that CC chemokine receptors (CCRs 1, 2, 3, 5)
      and ligands (macrophage inflammatory protein-1alpha, RANTES) are expressed at
      higher levels in dystrophic than in wild-type muscles across age groups (6, 12,
      and 24 wk). Moreover, chemokine ligand expression and muscle inflammation are
      significantly higher in dystrophic diaphragms than in limb muscles of the same
      animals. In vitro, CCR1 is constitutively expressed by cultured primary
      diaphragmatic myotubes. Stimulation of myotubes by proinflammatory cytokines
      (tumor necrosis factor-alpha, interleukin-1alpha, interferon-gamma) found within
      the in vivo dystrophic muscle environment, upregulates CCR1 in mdx and wild-type
      cultures, and also increases expression of its ligand RANTES to a significantly
      greater degree in the mdx group. Taken together, our results suggest that CC
      chemokines may play an important role in sustaining inflammation within the mdx
      diaphragm, which could help account for its more severe phenotype and also offer
      a target for therapeutic intervention in Duchenne patients.

PMID- 15860798
TI  - Development and functional consequences of LPS tolerance in sinusoidal
      endothelial cells of the liver.
AB  - Kupffer cells and liver sinusoidal endothelial cells (LSEC) clear portal venous
      blood from gut-derived bacterial degradation products such as lipopolysaccharide
      (LPS) without inducing a local inflammatory reaction. LPS tolerance was reported
      for Kupffer cells, but little is known whether sensitivity of LSEC toward LPS is
      dynamically regulated. Here, we demonstrate that LSEC react to LPS directly as a
      function of constitutive Toll-like receptor 4 (TLR4)/CD14 expression but gain a
      LPS-refractory state upon repetitive stimulation without loss of scavenger
      activity. LPS tolerance in LSEC is characterized by reduced nuclear localization
      of nuclear factor-kappaB upon LPS rechallenge. In contrast to monocytes, however,
      TLR4 surface expression of LSEC is not altered by LPS stimulation and thus does
      not account for LPS tolerance. Mechanistically, LPS tolerance in LSEC is linked
      to prostanoid production and may account for cross-tolerance of LPS-treated LSEC
      to interferon-gamma stimulation. Functionally, LPS tolerance in LSEC results in
      reduced leukocyte adhesion following LPS rechallenge as a consequence of
      decreased CD54 surface expression. Furthermore, LPS tolerance is operative in
      vivo, as we observed by intravital microscopy-reduced leukocyte adhesion to LSEC
      and improved sinusoidal microcirculation in the liver after repetitive LPS
      challenges. Our results support the notion that LPS tolerance in organ-resident
      scavenger LSEC contributes to local hepatic control of inflammation.

PMID- 15860800
TI  - Measuring NHS productivity.

PMID- 15860799
TI  - Phosphoinositide-3 kinases critically regulate the recruitment and survival of
      eosinophils in vivo: importance for the resolution of allergic inflammation.
AB  - The phosphatidylinositol-3 kinase (PI3K) family of signaling enzymes plays a
      crucial role in leukocyte recruitment and activation and hence, likely regulates
      the induction and propagation phases of inflammation. However, little data have
      emerged showing a role for these processes in the resolution phase in models of
      in vivo inflammation. Here, we have evaluated the role of PI3K for the migration
      and survival of eosinophils in a model of allergic pleurisy in mice. Eosinophil
      accumulation in PI3Kgamma-deficient mice was inhibited at 48 h, as compared with
      wild-type mice but not at earlier time-points (6 and 24 h). Experiments with
      adoptive transfer of bone marrow showed that PI3Kgamma in eosinophils but not in
      non-bone marrow-derived cells was required for their accumulation. Systemic
      treatment with PI3K inhibitors before antigen challenge prevented the recruitment
      of eosinophils. This was associated with decreased Akt phosphorylation,
      interleukin-5 production, and eosinophil release from the bone marrow. Treatment
      with PI3K inhibitors 24 h after antigen challenge markedly cleared the
      accumulated eosinophils, an effect associated with inhibition of Akt
      phosphorylation and an increased number of apoptotic events. Altogether, our data
      demonstrate an important role of PI3Kgamma for the maintenance of eosinophilic
      inflammation in vivo, whereas other isoforms of PI3K may be relevant for the
      recruitment process.

PMID- 15860801
TI  - Treatment of staphylococcal infection.

PMID- 15860802
TI  - Surveying the literature from animal experiments.

PMID- 15860803
TI  - Childhood obstructive sleep apnoea.

PMID- 15860804
TI  - Radiotherapy for the future.

PMID- 15860806
TI  - Parents wrongfully accused of child abuse cannot sue doctors.

PMID- 15860807
TI  - Institute recommends a global health corps for AIDS.

PMID- 15860808
TI  - US academy calls for new bodies to oversee stem cell research.

PMID- 15860809
TI  - Emergency contraception is under attack by US pharmacists.

PMID- 15860812
TI  - Drug company is censured for offering perks to prescribing nurses.

PMID- 15860811
TI  - Data for evaluating drugs is often poor, say experts.

PMID- 15860813
TI  - EU starts campaign on noise before it introduces lower workplace limits.

PMID- 15860814
TI  - Regulator restricts use of SSRIs in children.

PMID- 15860815
TI  - Pathologists shed new light on Sally Clark case.

PMID- 15860816
TI  - Parents fail to overturn ruling not to resuscitate baby.

PMID- 15860818
TI  - Queensland considers how to improve checks on foreign doctors.

PMID- 15860819
TI  - Nowhere to go.

PMID- 15860820
TI  - Avoiding the issues.

PMID- 15860821
TI  - The view from abroad.

PMID- 15860822
TI  - GPs should take a bigger role in care of long term mentally ill patients.

PMID- 15860823
TI  - New era of public access to federally funded trials begins.

PMID- 15860824
TI  - Medical editors issue guidance on ghost writing.

PMID- 15860825
TI  - Reducing the time from soup to nuts.

PMID- 15860826
TI  - Ciprofloxacin interacts with thyroid replacement therapy.

PMID- 15860828
TI  - Illness trajectories and palliative care.

PMID- 15860827
TI  - Randomised controlled trial of calcium and supplementation with cholecalciferol
      (vitamin D3) for prevention of fractures in primary care.
AB  - OBJECTIVE: To assess whether supplementation with calcium and cholecaliferol
      (vitamin D3) reduces the risk of fracture in women with one or more risk factors
      for fracture of the hip. DESIGN: Pragmatic open randomised controlled trial.
      SETTING: Practice nurse led clinics in primary care. PARTICIPANTS: 3314 women
      aged 70 and over with one or more risk factors for hip fracture: any previous
      fracture, low body weight (< 58 kg), smoker, family history of hip fracture, or
      fair or poor self reported health. INTERVENTION: Daily oral supplementation using
      1000 mg calcium with 800 IU cholecaliferol and information leaflet on dietary
      calcium intake and prevention of falls, or leaflet only (control group). MAIN
      OUTCOME MEASURES: Primary outcome measure was all clinical fractures and
      secondary outcome measures were adherence to treatment, falls, and quality of
      life (measured with the SF-12). RESULTS: 69% of the women who completed the
      follow-up questionnaire at 24 months were still taking supplements (55% with
      inclusion of randomised participants known to be alive). After a median follow-up
      of 25 months (range 18 to 42 months), clinical fracture rates were lower than
      expected in both groups but did not significantly differ for all clinical
      fractures (odds ratio for fracture in supplemented group 1.01, 95% confidence
      interval 0.71 to 1.43). The odds ratio for hip fracture was 0.75 (0.31 to 1.78).
      The odds of a woman having a fall at six and 12 months was 0.99 and 0.98,
      respectively. Quality of life did not significantly differ between the groups.
      CONCLUSION: We found no evidence that calcium and vitamin D supplementation
      reduces the risk of clinical fractures in women with one or more risk factors for
      hip fracture. Registration ISRCTN26118436, controlled trials registry.

PMID- 15860829
TI  - Fatigue and somatic symptoms.

PMID- 15860830
TI  - Health inequalities and New Labour: how the promises compare with real progress.

PMID- 15860832
TI  - Reduction in mortality from breast cancer: presentation of benefits and harms
      needs to be balanced.

PMID- 15860831
TI  - Readers guide to critical appraisal of cohort studies: 3. Analytical strategies
      to reduce confounding.

PMID- 15860833
TI  - Reduction in mortality from breast cancer: fall in use of hormones could have
      reduced breast cancer mortality.

PMID- 15860834
TI  - Reduction in mortality from breast cancer: decrease with screening was marked in
      younger age group.

PMID- 15860835
TI  - Partnerships with African hospitals may improve health.

PMID- 15860836
TI  - Changes to India's patent law: unaffordable drugs may discourage diagnosing HIV
      and increase transmission.

PMID- 15860837
TI  - Changes to India's patent law: integrated approach is needed.

PMID- 15860838
TI  - Reduction in mortality from breast cancer: reasons for improved survival are more
      complex than suggested.

PMID- 15860841
TI  - Self harm was misrepresented (again).

PMID- 15860846
TI  - Medicinal cannabis in oncology practice: still a bridge too far?

PMID- 15860847
TI  - Hepatocellular carcinoma: the need for progress.

PMID- 15860848
TI  - Type II chemotherapy-related cardiac dysfunction: time to recognize a new entity.

PMID- 15860849
TI  - The combined percentage of Gleason patterns 4 and 5 is the best predictor of
      cancer progression after radical prostatectomy.
AB  - PURPOSE: Clinical outcome is variable in prostate cancer patients treated with
      radical prostatectomy. The Gleason histologic grade of prostatic adenocarcinoma
      is one of the strongest predictors of biologic aggressiveness of prostate cancer.
      We evaluated the significance of the relative proportion of high-grade cancer
      (Gleason patterns 4 and/or 5) in predicting cancer progression in prostate cancer
      patients treated with radical prostatectomy. PATIENTS AND METHODS: Radical
      prostatectomy specimens from 364 consecutive prostate cancer patients were
      totally embedded and whole mounted. Various clinical and pathologic
      characteristics were analyzed. All pathologic data, including Gleason grading
      variables, were collected prospectively. RESULTS: A multiple-factor analysis was
      performed that included the combined percentage of Gleason patterns 4 and 5,
      Gleason score, tumor stage, surgical margin status, preoperative prostate
      specific antigen (PSA), extraprostatic extension, and total tumor volume. Using
      Cox regression analysis with bootstrap resampling for predictor selection, we
      identified the combined percentage of Gleason patterns 4 and 5 (P < .0001) and
      total tumor volume (P = .009) as significant predictors of PSA recurrence.
      CONCLUSION: The combined percentage of Gleason patterns 4 and 5 is one of the
      most powerful predictors of patient outcome, and appears superior to conventional
      Gleason score in identifying patients at increased risk of disease progression.
      On the basis of our results, we recommend that the combined percentage of Gleason
      patterns 4 and 5 be evaluated in radical prostatectomy specimens. The amount of
      high-grade cancer in a prostatectomy specimen should be taken into account in
      therapeutic decision making and assessment of patient prognosis.

PMID- 15860851
TI  - Time from treatment to subsequent diagnosis of brain metastases in stage III non
      small-cell lung cancer: a retrospective review by the Southwest Oncology Group.
AB  - PURPOSE A retrospective review of the Southwest Oncology Group (SWOG) database
      was undertaken to review the incidence and timing of diagnosis of brain
      metastases in patients undergoing combined-modality therapy for stage III non
      small-cell lung cancer (NSCLC). PATIENTS AND METHODS Four hundred twenty-two
      eligible, assessable patients with stage IIIA/B NSCLC were treated on four SWOG
      protocols. Treatment varied with protocol but consisted of concurrent cisplatin
      etoposide and radiation in all patients, with a surgery arm in two of the four
      protocols. Results Of the 422 total patients, 268 (64%) have experienced disease
      progression; 54 relapses (20%) were in brain only, 17 (6.5%) were in brain and
      other sites simultaneously, and 197 (63.5%) were in sites other than brain. Of
      the 268 patients with disease progression, progression in the brain only, in the
      brain and other sites, and not in the brain occurred in 20%, 6%, and 74% of
      patients, respectively. Time from treatment to diagnosis of disease progression
      in the brain in 71 patients was as follows: during treatment, 16 relapses
      (22.5%); 0 to 16 weeks after treatment, 17 relapses (24%); 16 weeks to 6 months
      after treatment, 10 relapses (14%); 6 to 12 months after treatment, 16 relapses
      (22.5%); and more than 12 months after treatment, 12 relapses (17%). Nonsquamous
      histology and young patient age were the only significant predictors for
      increased risk of early relapse with brain metastases. CONCLUSION Brain
      metastases often develop early in the course of treatment for stage IIIA/B NSCLC.
      The statistical designs of ongoing trials of prophylactic cranial irradiation in
      stage III NSCLC have taken this into account.

PMID- 15860850
TI  - Natural history of rising serum prostate-specific antigen in men with castrate
      nonmetastatic prostate cancer.
AB  - PURPOSE: To describe the natural history of nonmetastatic prostate cancer and
      rising prostate-specific antigen (PSA) despite androgen deprivation therapy.
      PATIENTS AND METHODS: The 201 patients in this report were the placebo control
      group from an aborted randomized controlled trial to evaluate the effects of
      zoledronic acid on time to first bone metastasis in men with prostate cancer, no
      bone metastases, and rising PSA despite androgen deprivation therapy.
      Relationships between baseline covariates and clinical outcomes were assessed by
      Cox proportional hazard analyses. Covariates in the model were baseline PSA,
      Gleason sum, history of bilateral orchiectomies, regional lymph node metastases
      at diagnosis, prior prostatectomy, time from androgen deprivation therapy to
      random assignment, time from diagnosis to random assignment, and PSA velocity.
      RESULTS: At 2 years, 33% of patients had developed bone metastases. Median bone
      metastasis-free survival was 30 months. Median time to first bone metastases and
      overall survival were not reached. Baseline PSA level greater than 10 ng/mL
      (relative risk, 3.18; 95% CI, 1.74 to 5.80; P < .001) and PSA velocity (4.34 for
      each 0.01 increase in PSA velocity; 95% CI, 2.30 to 8.21; P < .001) independently
      predicted shorter time to first bone metastasis. Baseline PSA and PSA velocity
      also independently predicted overall survival and metastasis-free survival. Other
      covariates did not consistently predict clinical outcomes. CONCLUSION: Men with
      nonmetastatic prostate cancer and rising PSA despite androgen deprivation therapy
      have a relatively indolent natural history. Baseline PSA and PSA velocity
      independently predict time to first bone metastasis and survival.

PMID- 15860852
TI  - Results of the Dutch National study of the palliative effect of irradiation using
      two different treatment schemes for non-small-cell lung cancer.
AB  - PURPOSE: A national multicenter randomized study compared the efficacy of 2 x 8
      Gy versus our standard 10 x 3 Gy in patients with inoperable stage IIIA/B (with
      an Eastern Cooperative Oncology Group score of 3 to 4 and/or substantial weight
      loss) and stage IV non-small-cell lung cancer. PATIENTS AND METHODS: Between
      January 1999 and June 2002, 297 patients were eligible and randomized to receive
      either 10 x 3 Gy or 2 x 8 Gy by external-beam irradiation. The primary end point
      was a patient-assessed score of treatment effect on seven thoracic symptoms using
      an adapted Rotterdam Symptom Checklist. Study sample size was determined based on
      an average total symptom score difference of more than one point over the initial
      39 weeks post-treatment. The time course of symptom scores were also evaluated,
      and other secondary end points were toxicity and survival. RESULTS: Both
      treatment arms were equally effective, as the average total symptom score over
      the initial 39 weeks did not differ. However, the pattern in time of these scores
      differed significantly (P < .001). Palliation in the 10 x 3-Gy arm was more
      prolonged (until week 22) with less worsening symptoms than in 2 x 8-Gy. Survival
      in the 10 x 3-Gy arm was significantly (P = .03) better than in the 2 x 8-Gy arm
      with 1-year survival of 19.6% (95%CI, 14.1% to 27.3%) v 10.9% (95%CI, 6.9% to
      17.3%). CONCLUSION: The 10 x 3-Gy radiotherapy schedule is preferred over the 2 x
      8-Gy schedule for palliative treatment, as it improves survival and results in a
      longer duration of the palliative response.

PMID- 15860853
TI  - Neoadjuvant percutaneous 4-hydroxytamoxifen decreases breast tumoral cell
      proliferation: a prospective controlled randomized study comparing three doses of
      4-hydroxytamoxifen gel to oral tamoxifen.
AB  - PURPOSE: Two chemoprevention randomized studies using tamoxifen showed drug
      efficacy; however, adverse effects such as hot flushes, endometrial cancer, and
      above all, thromboembolism, remain a problem. 4 hydroxytamoxifen (4-OHT) is a
      very active metabolite of tamoxifen. This randomized study was designed to
      analyze if 4-OHT gel, administered percutaneously on the breast skin, can inhibit
      the proliferation of malignant breast cells to the same extent as orally
      administered tamoxifen. PATIENTS AND METHODS: Fifty-five postmenopausal women
      with an invasive estrogen receptor-positive breast cancer were randomly assigned
      to receive (for 2 to 3 weeks) either 4-OHT gel (0.5, 1, or 2 mg/d) or oral
      tamoxifen (20 mg/d) or no treatment. Response was evaluated using proliferation
      markers (Ki-67, proliferating cell nuclear antigen) and apoptosis markers in
      tissue samples obtained by Tru-cut biopsy before treatment, and at surgery after
      treatment. RESULTS: Administration of 4-OHT gel resulted in reductions in tumor
      tissue proliferation indexes (Ki-67 and PCNA), with approximate equivalence
      between the 1.0 mg/d or 2.0 mg/d 4-OHT dose, and oral tamoxifen, but had no
      effect on apoptotic markers. Plasma levels of 4-OHT were consistently higher in
      the oral tamoxifen group than in the gel groups. No dose-related pattern was
      shown for estrogen or progesterone receptor levels, and topical 4-OHT gel
      appeared to be generally well tolerated. Hot flushes are as common in the two
      higher gel doses as with tamoxifen. CONCLUSION: Percutaneous 4-OHT gel has a
      local impact on tumor proliferation. It could be tested in future prospective
      trials of chemoprevention or ductal carcinoma in situ adjuvant hormonotherapy.

PMID- 15860854
TI  - Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and
      cyclophosphamide as primary medical therapy in women with breast cancer: an anglo
      celtic cooperative oncology group study.
AB  - PURPOSE To compare the clinical and pathologic response rates of doxorubicin and
      cyclophosphamide (AC) with doxorubicin and docetaxel (AD) as primary chemotherapy
      in women with primary or locally advanced breast cancer. PATIENTS AND METHODS
      Eligible patients with histologically proven breast cancer with primary tumors
      >/= 3 cm, inflammatory or locally advanced disease, and no evidence of metastases
      were randomly assigned to receive a maximum of six cycles of either doxorubicin
      (60 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) administered intravenously (IV)
      every 3 weeks or doxorubicin (60 mg/m(2)) plus docetaxel (75 mg/m(2)) IV every 3
      weeks, followed by surgery on completion of chemotherapy. Results A total of 363
      patients were randomly assigned to AC (n = 180) or AD (n = 183). A complete
      clinical response was observed in 17% and 20% of patients treated with AC and AD,
      respectively (P = .42). Overall (complete and partial) clinical response rates
      for AC and AD were 61% and 70%, respectively (P = .06). There was no significant
      difference in either the pathologic complete response rates in the breast with AC
      (24%) and AD (21%; P = .61) or in the number of patients with positive axillary
      nodes at surgery with AC (61%) and AD (66%; P = .28). At a median follow-up of 32
      months, there is no significant difference between the two groups for the number
      of relapses. CONCLUSION In contrast to the positive results reported for
      sequential docetaxel after AC as primary chemotherapy of breast cancer, our data
      do not suggest a benefit for simultaneous AD over AC.

PMID- 15860855
TI  - Mitotic index and benefit of adjuvant anthracycline-based chemotherapy in
      patients with early breast cancer.
AB  - PURPOSE: We have evaluated whether the mitotic index could predict the benefit of
      adjuvant anthracycline-based chemotherapy in patients with early breast cancer
      who are eligible for adjuvant chemotherapy according to Saint Gallen guidelines.
      PATIENTS AND METHODS: A total of 937 patients from a single institution were
      included in two randomized trials that compared adjuvant anthracycline-based
      chemotherapy with no chemotherapy. These patients account for 83% of the overall
      population included in these trials. The first trial included premenopausal
      patients with node-negative disease, and the second one included postmenopausal
      patients, regardless of lymph node status. The treatment benefit was assessed
      according to the number of mitoses per field (x400). RESULTS: The mitotic index
      was assessable in 888 patients (94%). All the patients presented as either node
      positive or an average-risk breast cancer according to 2003 Saint Gallen
      consensus conference guidelines. The 5-year overall survival rates were 91% and
      87% for patients treated or not with adjuvant chemotherapy (P = .09). In patients
      with low/medium mitotic index (< three mitoses/field; n = 450), the 5-year
      overall survival rate was 95% for patients treated or not with adjuvant
      chemotherapy (P = .56). In patients with high mitotic index (>/= three
      mitoses/field; n = 438), the 5-year overall survival rates were 86% and 79% for
      patients treated or not treated with adjuvant chemotherapy, respectively (P =
      .02). CONCLUSION: A high mitotic index is associated with the efficacy of
      adjuvant anthracycline-based chemotherapy in patients eligible for adjuvant
      chemotherapy in daily practice.

PMID- 15860856
TI  - Patterns and correlates of local therapy for women with ductal carcinoma-in-situ.
AB  - PURPOSE: Concerns have been raised about the quality of treatment for women with
      ductal carcinoma-in-situ (DCIS) because persistent high rates of mastectomy
      suggest overtreatment, whereas lower than expected rates of radiation therapy
      after breast-conserving surgery (BCS) suggest undertreatment. PATIENTS AND
      METHODS: All women with DCIS diagnosed in 2002 and who reported to the Detroit
      and Los Angeles Surveillance, Epidemiology, and End Results (SEER) registries
      were identified and surveyed shortly after receipt of surgery (response rate,
      79.7%; n = 817). Analyses were restricted to patients with DCIS (n = 659)
      indicated by SEER stage data. RESULTS: Only 14.0% of patients at lowest risk of
      recurrence (based on tumor size and histologic grade) received a mastectomy
      compared with 22.8% and 52.6% of patients at intermediate and highest risk (P <
      .001). Only 13.1% of patients who were not influenced or slightly influenced by
      concerns about recurrence received mastectomy compared with 48.8% of women who
      were greatly influenced by this concern (P < .001). A between-geographic site
      difference in receipt of radiation after BCS was observed for the lowest risk
      group (38.9% in Los Angeles v 70.5% in Detroit) but not for the highest risk
      group (80.2% in Los Angeles v 85.9% in Detroit, P = .006 for site and risk group
      differences). Between-site differences in receipt of radiation after BCS were
      consistent with patient recall of surgeon discussions about treatment.
      CONCLUSION: Surgeons are tailoring their recommendations for local therapy
      options for DCIS based on important clinical factors. Patient attitudes also play
      an important role in treatment decisions. The substantial influence of both
      surgeon opinion and patient attitudes should temper concerns about the quality of
      treatment for women with DCIS.

PMID- 15860858
TI  - Xerostomia following radiotherapy of the head and neck affects vocal function.
AB  - PURPOSE: To investigate whether xerostomia induced by wide-field radiotherapy
      (RT) of the head and neck affects vocal function. PATIENTS AND METHODS: We
      conducted a retrospective cohort study comparing 20 patients with early glottic
      cancer treated by limited RT of the larynx to 20 patients receiving wide-field RT
      of the primary tumor site and the lymphatic system of the entire head and neck,
      including the salivary glands. Salivary and vocal functions, as well as responses
      to questionnaires on xerostomia and quality of life were compared between groups.
      Twenty healthy volunteers matched for age, sex, and smoking status were included
      as controls. RESULTS: The wide-field RT patients showed high xerostomia-related
      symptom scores and significantly lower values of whole salivary flow rate
      compared to the limited RT and healthy patients (P < .001). Subjective vocal
      dysfunction and stroboscopic abnormality were observed in the wide-field RT group
      (P < .05), but acoustic or aerodynamic profiles showed no significant difference
      among groups (P > .05). Subjective and objective salivary gland hypofunction was
      significantly correlated to vocal dysfunction. CONCLUSION: Our results suggest
      that xerostomia following extensive RT of the head and neck can affect vocal
      function. In the treatment of head and neck malignancies, efforts to prevent post
      RT xerostomia would be anticipated to contribute to the preservation of vocal
      function.

PMID- 15860857
TI  - Concomitant boost radiation plus concurrent cisplatin for advanced head and neck
      carcinomas: radiation therapy oncology group phase II trial 99-14.
AB  - PURPOSE: To investigate the feasibility of combining concomitant boost
      accelerated radiation regimen (AFX-C) with cisplatin and to assess its toxicity
      and the relapse pattern and survival in patients with advanced head and neck
      carcinoma (HNC). PATIENTS AND METHODS: Between April and November of 2000, 84
      patients with stage III to IV HNC who met the eligibility criteria were enrolled;
      76 of these patients were analyzable. Radiation consisted of 72 Gy in 42
      fractions over 6 weeks (daily for 3.5 weeks, then twice a day for 2.5 weeks).
      Cisplatin dose was 100 mg/m(2) on days 1 and 22. Tumor and clinical status were
      assessed, and acute late toxicities were graded. RESULTS: Sixty-five patients
      (86%) received both radiation and chemotherapy per protocol or with minor
      variations. The estimated 2-year locoregional relapse and distant metastasis
      rates were 34.7% and 16.1%, respectively. The estimated 2-year overall survival
      and disease-free survival rates were 71.6% and 53.5%, respectively. Three
      patients (4%) died of complications, 19 patients (25%) had acute grade 4
      toxicity, and 49 patients (64%) had acute grade 3 toxicity. The 2-year cumulative
      incidence of late grade 3 to 5 toxicities was 51.3%. CONCLUSION: These data
      showed that it was feasible to combine AFX-C with cisplatin. The compliance to
      therapy was high, and the locoregional control and survival rates achieved
      compared favorably with AFX-C alone or other concurrent chemoradiation regimens
      tested by the Radiation Therapy Oncology Group. A phase III trial comparing AFX-C
      plus cisplatin against standard radiation plus cisplatin is ongoing to determine
      whether the use of AFX-C in the concurrent chemoradiation setting further
      improves outcome.

PMID- 15860859
TI  - Central venous lines in children with lesser risk acute lymphoblastic leukemia:
      optimal type and timing of placement.
AB  - PURPOSE: In pediatric patients with acute lymphoblastic leukemia (ALL), the
      optimal time for central venous line (CVL) insertion and the optimal type of CVL
      (internal v external) is unclear. This study was undertaken to compare
      complication rates between early versus late line insertion, and between internal
      versus external lines in children with lesser risk ALL. PATIENTS AND METHODS: We
      performed a retrospective analysis of patients enrolled onto Pediatric Oncology
      Group (POG) protocol 9201. Data regarding demographics, CVL types and insertion
      dates, blood counts, and complications were reviewed through week 25 of therapy.
      RESULTS: Of 697 patients enrolled onto POG protocol 9201, 362 patients had
      sufficient data for analysis. When compared to late line placement (> day 15 of
      induction), early CVL placement (</= day 15 of induction) was associated with an
      increased risk of having a positive blood culture (odds ratio, 2.2; 95% CI, 1.0
      to 5.0; P = .05). When compared with internal CVLs ("ports"), external CVLs were
      associated with a positive blood culture (odds ratio, 3.1; 95% CI, 1.3 to 7.5; P
      = .01), thrombosis (odds ratio, 3.9; 95% CI, 1.5 to 10.3; P = .006), and CVL
      removal (odds ratio, 5.6; 95% CI, 2.7 to 11.6; P < .001). CONCLUSION: In
      pediatric patients with lesser risk ALL, internal lines (ports) should be the
      preferred CVL type due to a lower risk of infectious and thrombotic
      complications. In addition, CVLs placed early in induction are associated with a
      higher risk of positive blood culture than those placed later in induction.

PMID- 15860860
TI  - Increased fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) uptake in childhood CNS
      tumors is correlated with malignancy grade: a study with FDG positron emission
      tomography/magnetic resonance imaging coregistration and image fusion.
AB  - PURPOSE Positron emission tomography (PET) has been used in grading of CNS tumors
      in adults, whereas studies of children have been limited. PATIENTS AND METHODS
      Nineteen boys and 19 girls (median age, 8 years) with primary CNS tumors were
      studied prospectively by fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) PET with (n
      = 16) or without (n = 22) H(2)(15)O-PET before therapy. Image processing included
      coregistration to magnetic resonance imaging (MRI) in all patients. The FDG
      uptake in tumors was semiquantitatively calculated by a region-of-interest-based
      tumor hotspot/brain index. Eight tumors without histologic confirmation were
      classified as WHO grade 1 based on location, MRI, and clinical course (22 to 42
      months). Results Four grade 4 tumors had a mean index of 4.27 +/- 0.5, four grade
      3 tumors had a mean index of 2.47 +/- 1.07, 10 grade 2 tumors had a mean index of
      1.34 +/- 0.73, and eight of 12 grade 1 tumors had a mean index of -0.31 +/- 0.59.
      Eight patients with no histologic confirmation had a mean index of 1.04. For
      these 34 tumors, FDG uptake was positively correlated with malignancy grading (n
      = 34; r = 0.72; P < .01), as for the 26 histologically classified tumors (n = 26;
      r = 0.89; P < .01). The choroid plexus papilloma (n = 1) and the pilocytic
      astrocytomas (n = 3) had a mean index of 3.26 (n = 38; r = 0.57; P < .01).
      H(2)(15)O-uptake showed no correlation with malignancy. Digitally performed
      PET/MRI coregistration increased information on tumor characterization in 90% of
      cases. CONCLUSION FDG PET of the brain with MRI coregistration can be used to
      obtain a more specific diagnosis with respect to malignancy grading. Improved
      PET/MRI imaging of the benign hypermetabolic tumors is needed to optimize
      clinical use.

PMID- 15860861
TI  - Expression of interleukin-10 splicing variants is a positive prognostic feature
      in relapsed childhood acute lymphoblastic leukemia.
AB  - PURPOSE: Biologic features of hematologic malignancies have prognostic
      implications and are essential elements in the design of current therapeutic
      trials. This study aimed to determine the expression of a splicing-derived
      variant of interleukin (IL) -10 in leukemic cells and its clinical relevance in
      children with acute lymphoblastic leukemia (ALL) at first relapse. PATIENTS AND
      METHODS: Between January 1997 and December 2001, bone marrow (BM) samples were
      collected from 98 children with first relapse of ALL at diagnosis. These patients
      were enrolled in the relapse trial ALL-REZ BFM (ALL-Relapse Berlin-Frankfurt
      Munster) 95 and 96. The detection of IL-10 isoforms in leukemic cells of BM
      samples were performed by conventional reverse transcriptase polymerase chain
      reaction and by immunoblotting. RESULTS: IL-10 was detected in 93.9% BM samples.
      In addition to expressing full-length IL-10, a new splicing-derived IL-10 variant
      (termed IL-10delta3) that lacked the entire exon 3 was identified in leukemic
      cells. The IL-10delta3 variant was found in 80.4% of BM samples. Most
      importantly, expression of IL-10delta3 was associated with a significantly better
      response to chemotherapy (P = .001) and probability of event-free survival (P =
      .01) at 5 years. CONCLUSION: These results indicate that splicing-derived IL-10
      isoforms may modulate IL-10-mediated biologic effects and therapeutic efficacy in
      lymphatic disease, and expression of IL-10delta3 is a positive prognostic feature
      in relapsed childhood ALL.

PMID- 15860864
TI  - Side effects and cancer-related stress determine quality of life in long-term
      survivors of testicular cancer.
AB  - PURPOSE: The prevalence of long-term survivors after treatment for testicular
      cancer (TC) is increasing, and most studies display normal or only slightly
      reduced quality of life (QOL) in TC survivors (TCSs). Impaired QOL is claimed to
      be associated with treatment modality and its side effects, although most studies
      in this field can be criticized for various methodologic shortcomings. We wanted
      to examine variation in long-term QOL in TCSs in relation to TC treatment
      modality, side effects, and TC-related stress in a large population. PATIENTS AND
      METHODS: QOL, side effects, and TC-related stress were self-rated by a
      questionnaire at a mean of 11 years of follow-up in 1,409 TCSs treated from 1980
      to 1994. Norm data was obtained from 2,678 males who were representative of the
      general population. QOL was measured with the Short Form-36 (SF-36), and TC
      related stress was measured with the Impact of Event Scale. RESULTS: There were
      no clinically relevant differences in QOL between TCSs and age-adjusted norm
      data, although there was a slightly lowered SF-36 Physical Component Summary
      Score in TCSs. Variation of QOL in TCSs was related to self-reported side effects
      and TC-related stress but not to TC treatment modality. A significant association
      was found between side effects and TC-related stress. CONCLUSION: TCSs do not
      suffer long term from reduced QOL, and only minor differences in QOL were found
      between different treatment modalities. TCSs who report more side effects or TC
      related stress have increased risk for reduced QOL, but these associations are
      not explained by TC treatment modalities. Further QOL research in this area
      should explore vulnerability factors for side effects and TC-related stress.

PMID- 15860862
TI  - Role of the CDKN2A locus in patients with multiple primary melanomas.
AB  - PURPOSE: We have studied a consecutive case series of patients with multiple
      primary melanoma (MPM) for the involvement of the melanoma susceptibility loci
      CDKN2A and CDK4. PATIENTS AND METHODS: One hundred four MPM patients (81 patients
      with two primary melanomas, 14 with three, five with four, one with five, two
      with six, and one with seven) were included. RESULTS: Seven different CDKN2A
      germline mutations were identified in 17 patients (16.3%). In total, we
      identified 15 CDKN2A exon 2, one exon 1alpha missense mutation, and one exon
      1beta frameshift mutation. The age of onset was significantly lower and the
      number of primary melanomas higher in patients with mutations. CDKN2A mutations
      were more frequent in patients with familial history of melanoma (35.5%) compared
      with patients without (8.2%), with a relative risk (RR) of 4.32 (95% CI, 1.76 to
      10.64; P = .001), and in patients with more than two melanomas (39.1%) compared
      with patients with only two melanomas (10%) with an RR of 3.29 (95% CI, 1.7 to
      6.3; P = .002). The A148T polymorphism was more frequent in patients with MPMs
      than in the control population (P = .05). A variant of uncertain significance,
      A127S, was also detected in one patient. No CDK4 mutations were identified,
      suggesting that it has a low impact in susceptibility to MPM. CONCLUSION: MPM
      patients are good candidates for CDKN2A mutational screening. These patients and
      some of their siblings should be included in a program of specific follow-up with
      total body photography and digital dermoscopy, which will result in the early
      detection of melanoma in this subset of high-risk patients and improve phenotypic
      characterization.

PMID- 15860865
TI  - Evaluation of epothilone B analog in advanced soft tissue sarcoma: a phase II
      study of the phase II consortium.
AB  - PURPOSE: Epothilones are a new class of nontaxane tubulin polymerization agents
      that have activity in taxane-resistant tumors. Epothilone B (BMS-247550) is a
      semisynthetic analog of the natural product epothilone B. This study was
      performed to determine the activity of BMS-247550 in patients with soft tissue
      sarcomas (STSs) who had not received prior chemotherapy for metastatic disease.
      PATIENTS AND METHODS: Patients with measurable, advanced, or metastatic STS with
      no prior chemotherapy for metastatic disease were treated with BMS-2457550 50
      mg/m(2) intravenously during 1 hour every 21 days. All responses were confirmed 4
      weeks later. RESULTS: Thirty-one patients (median age, 54 years; range, 19 to 78
      years; 48% female) were entered onto the trial and were assessable for response.
      All but one patient had an Eastern Cooperative Oncology Group performance score
      of 0% or 1%, and 39% had received prior adjuvant chemotherapy. Mean follow-up was
      22 months, with a confirmed response rate of 6% (95% CI, 0% to 17%). Median time
      to progression was 4.5 months (95% CI, 1.9 to 8.3 months), and 1 year progression
      free survival was 17% (95% CI, 8% to 38%). Median survival was 16.4 months, with
      a 1-year survival of 61% (95% CI, 46% to 81%). Toxicity was mainly hematologic,
      with eight of 31 (26%) patients experiencing grade 3 to 4 leukopenia; 15 of 31
      patients (48%) experienced grade 3 to 4 neutropenia. The grade 3 to 4
      nonhematologic toxicities included neuropathies (26%), myalgia (13%), and fatigue
      (10%). CONCLUSION: BMS-247550 has limited activity against STSs when given in
      this dose and schedule. The clinical toxicity is similar to that of taxanes.

PMID- 15860863
TI  - Depression, correlates of depression, and receipt of depression care among low
      income women with breast or gynecologic cancer.
AB  - PURPOSE: To assess the prevalence of depression among low-income, ethnic minority
      women with breast or gynecologic cancer, receipt of antidepressant medications or
      counseling services, and correlates of depression. PATIENTS AND METHODS: Study
      patients were 472 women receiving cancer care in an urban public medical center.
      Women had a primary diagnosis of breast (stage 0 to III) or gynecologic cancer
      (International Federation of Gynecology and Obstetrics stage 0 to IIIB). A
      diagnostic depression screen and baseline questionnaire were administered before
      or during active treatment or during active follow-up. Self-report data were
      collected on receipt of depression treatment, use of supportive counseling, pain
      and receipt of pain medication, functional status and well-being, and perceived
      barriers to cancer care. RESULTS: Twenty-four percent of women reported moderate
      to severe levels of depressive disorder (30% of breast cancer patients and 17% of
      gynecologic cancer patients). Only 12% of women meeting criteria for major
      depression reported currently receiving medications for depression, and only 5%
      of women reported seeing a counselor or participating in a cancer support group.
      Neither cancer stage nor treatment status was correlated with depression. Primary
      diagnosis of breast cancer, younger age, greater functional impairment, poorer
      social and family well-being, anxiety, comorbid arthritis, and fears about
      treatment side effects were correlated with depression. CONCLUSION: Findings
      indicate that depressive disorder among ethnic minority, low-income women with
      breast or gynecologic cancer is prevalent and is correlated with pain, anxiety,
      and health-related quality of life. Because these women are unlikely to receive
      depression treatment or supportive counseling, there is a need for routine
      screening, evaluation, and treatment in this population.

PMID- 15860867
TI  - Randomized trial of hyperthermia and radiation for superficial tumors.
AB  - PURPOSE: Randomized clinical trials have demonstrated hyperthermia (HT) enhances
      radiation response. These trials, however, generally lacked rigorous thermal dose
      prescription and administration. We report the final results of a prospective
      randomized trial of superficial tumors (</= 3 cm depth) comparing radiotherapy
      versus HT combined with radiotherapy, using the parameter describing the number
      of cumulative equivalent minutes at 43 degrees C exceeded by 90% of monitored
      points within the tumor (CEM 43 degrees C T(90)) as a measure of thermal dose.
      METHODS: This trial was designed to test whether a thermal dose of more than 10
      CEM 43 degrees C T(90) results in improved complete response and duration of
      local control compared with a thermal dose of </= 1 CEM 43 degrees C T(90).
      Patients received a test dose of HT </= 1 CEM 43 degrees C T(90) and tumors
      deemed heatable were randomly assigned to additional HT versus no additional HT.
      HT was given using microwave spiral strip applicators operating at 433 MHz.
      RESULTS: One hundred twenty-two patients were enrolled; 109 (89%) were deemed
      heatable and were randomly assigned. The complete response rate was 66.1% in the
      HT arm and 42.3% in the no-HT arm. The odds ratio for complete response was 2.7
      (95% CI, 1.2 to 5.8; P = .02). Previously irradiated patients had the greatest
      incremental gain in complete response: 23.5% in the no-HT arm versus 68.2% in the
      HT arm. No overall survival benefit was seen. CONCLUSION: Adjuvant hyperthermia
      with a thermal dose more than 10 CEM 43 degrees C T(90) confers a significant
      local control benefit in patients with superficial tumors receiving radiation
      therapy.

PMID- 15860868
TI  - Catalytic subunit of human telomerase reverse transcriptase is an independent
      predictor of survival in patients undergoing curative resection of hepatic
      colorectal metastases: a multicenter analysis.
AB  - PURPOSE: To determine the role of the catalytic subunit of human telomerase
      reverse transcriptase (hTERT) in predicting survival after resection of hepatic
      colorectal metastases (CRM). PATIENTS AND METHODS: Two hundred one patients who
      underwent curative resection of hepatic CRM between 1990 and 2000 were identified
      from a multicenter database. The CRM were analyzed for hTERT nucleolar expression
      by standard immunohistochemical techniques. hTERT expression and known
      clinicopathologic factors of survival were examined. RESULTS: With a median
      follow-up of 80 months, 152 patients (75.6%) had died; the 5-year overall
      survival was 30.7%. On univariate analysis, number of metastases greater than two
      (P = .0005), extrahepatic disease (P = .0054), disease-free interval less than 12
      months (P = .006), carcinoembryonic antigen level greater than 200 ng/mL (P =
      .0071), and positive hTERT nucleolar staining (P < .0001) were associated with
      decreased survival. On multivariate analysis, three factors independently
      predicted survival: number of metastases (relative risk [RR] = 1.74; P = .0011);
      disease-free interval (RR = 1.70; P = .0035); and positive hTERT nucleolar
      staining (RR = 2.03; P < .0001). Patients with none or one of these factors had a
      5-year survival rate of 48%, whereas those with two or three of these factors had
      a 5-year survival of 15% (P < .0001). CONCLUSION: hTERT nucleolar expression is
      associated with worse survival after resection of hepatic CRM. hTERT expression
      in conjunction with number of hepatic metastases and disease-free interval may
      permit more accurate prediction of survival after resection of hepatic CRM.

PMID- 15860866
TI  - TGFBR1*6A may contribute to hereditary colorectal cancer.
AB  - PURPOSE: TGFBR16A is a tumor susceptibility gene that increases breast, colon,
      and ovarian cancer risk. Fourteen percent of the general population carries
      TGFBR16A, and TGFBR16A homozygotes have a greater than 100% increased colon
      cancer risk compared with noncarriers. Low-penetrance genes such as TGFBR16A may
      account for a sizable proportion of familial colorectal cancer occurrences. To
      test this hypothesis, we determined whether TGFBR16A contributes to a proportion
      of mismatch repair (MMR) gene mutation-negative hereditary nonpolyposis
      colorectal cancer (HNPCC) patients. PATIENTS AND METHODS: A case-case study was
      performed of 208 index patients with HNPCC meeting the Amsterdam criteria.
      Patients were examined for mutations and genomic rearrangements in the MLH1,
      MSH2, and MSH6 genes and genotyped for TGFBR16A. Tumor microsatellite instability
      status was available for 95 patients. RESULTS: A total of 144 patients (69.2%)
      carried a deleterious mutation and were classified as positive for MMR gene
      mutation; 64 patients (30.8%) had no evidence of mutations and were classified as
      MMR negative. TGFBR16A allelic frequency was significantly higher among MMR
      negative patients (0.195) than among MMR-positive patients (0.104; P = .011). The
      proportion of TGFBR16A homozygotes was nine-fold higher among MMR-negative (6.3%)
      than among MMR-positive patients (0.7%; P = .032). The highest TGFBR16A allelic
      frequency was found among MMR-negative patients with tumors exhibiting no
      microsatellite instability (0.211), and the lowest frequency was found among MMR
      positive patients with tumors exhibiting microsatellite instability (0.121); the
      difference was not statistically significant (P = .17). CONCLUSION: TGFBR16A may
      be causally responsible for a proportion of HNPCC occurrences.

PMID- 15860869
TI  - Clinicopathologic behavior of gastric adenocarcinoma in Hispanic patients:
      analysis of a single institution's experience over 15 years.
AB  - PURPOSE: To determine the clinicopathologic behavior of gastric adenocarcinoma in
      Hispanics by comparing Hispanic and non-Hispanic patients treated at a single
      cancer center. PATIENTS AND METHODS: Medical records of patients with invasive
      gastric cancer treated from 1985 to 1999 were reviewed. Diagnoses were
      pathologically confirmed. Differences in categorical variables were assessed
      using the chi(2) test. Logistic regression was used for multivariate analyses.
      Median survival was estimated using the Kaplan-Meier method. Cox proportional
      hazards modeling was used to assess the impact of covariates. RESULTS: Of 1,897
      patients, 301 (15.9%) were Hispanic. Hispanics were significantly younger at
      diagnosis than non-Hispanic whites (53.1 +/- 14.4 years v 59.4 +/- 12.7 years,
      respectively; P < .005) or African Americans (57.6 +/- 15.3 years, P < .005).
      Hispanics were less likely to have proximal gastric cancers compared with whites
      (38.9% v 59.5%, respectively; P < .005). Hispanics were more likely to have
      mucinous/signet-ring type histology (42.5%) than whites (27.4%) and African
      Americans (32.5%; P < .005). Hispanics were more likely to require total
      gastrectomy (51%) compared with whites (38%), African Americans (38%), and Asians
      (36%; P = .039). Among patients with metastases at diagnosis, Hispanics were less
      likely to have liver metastasis than whites (30% v 44%, respectively; P = .009)
      but more likely to have peritoneal metastasis than whites and African Americans
      (54% v 41% and 47%, respectively; P = .002). In Cox analyses, Asian race, earlier
      stage, papillary/tubular histology, distal location, and younger age were
      favorable predictors of survival. CONCLUSION: Hispanic ethnicity does not impact
      survival in gastric adenocarcinoma. However, histology, metastasis pattern, tumor
      localization, and other clinical parameters differ sufficiently to warrant
      further investigation into the epidemiology, pathogenesis, and molecular biology
      of gastric cancer in this population.

PMID- 15860870
TI  - Capecitabine as first-line treatment for patients older than 70 years with
      metastatic colorectal cancer: an oncopaz cooperative group study.
AB  - PURPOSE: To determine the tolerability of capecitabine in elderly patients with
      advanced colorectal cancer (CRC). PATIENTS AND METHODS: Fifty-one patients with
      advanced CRC who were >/= 70 years and considered ineligible for combination
      chemotherapy received oral capecitabine 1,250 mg/m(2) twice daily on days 1 to 14
      every 3 weeks. Patients with a creatinine clearance of 30 to 50 mL/min received a
      dose of 950 mg/m(2) twice daily. RESULTS: A total of 248 cycles of capecitabine
      were administered (median, five cycles; range, one to eight cycles). The overall
      response rate was 24% (95% CI, 15% to 41%), including two complete responses (CR;
      4%) and 10 partial responses (PR; 20%). Disease control (CR + PR + stable
      disease) was achieved in 67% of patients. The median times to disease progression
      and overall survival were 7 months (95% CI, 6.4 to 9.5 months) and 11 months (95%
      CI, 8.6 to 13.3 months), respectively. Of the 35 patients evaluated for clinical
      benefit response, 14 (40%; 95% CI, 24% to 58%) showed clinical benefit.
      Capecitabine was well tolerated. Treatment-related grade 3 and 4 adverse events
      were observed in only six patients (12%), and the most common events were
      diarrhea, hand-foot syndrome, and thrombocytopenia. One patient (2%) had an
      episode of angina, but no treatment-related deaths were reported. CONCLUSION: Our
      findings suggest that capecitabine is effective and well tolerated in elderly
      patients with advanced CRC who are considered ineligible for combination
      chemotherapy.

PMID- 15860871
TI  - Systematic review of barriers to the recruitment of older patients with cancer
      onto clinical trials.
AB  - PURPOSE: Older patients are significantly underrepresented in cancer clinical
      trials. A literature review was undertaken to identify the barriers that impede
      the accrual of this vulnerable population onto clinical trials and to determine
      what specific strategies are needed to improve the representation of older
      patients in research studies. METHODS: A systematic literature search was
      undertaken using several different strategies to identify relevant articles.
      RESULTS: Nine of 31 relevant papers from 159 citations were included. Age is a
      significant barrier to recruitment; only a quarter to one third of potentially
      eligible older patients are enrolled onto trials. Physicians' perceptions,
      protocol eligibility criteria with restrictions on comorbid conditions, and
      functional status to optimize treatment tolerability are the most important
      reasons resulting in the exclusion of older patients. Other barriers include the
      lack of social support and the need for extra time and resources to enroll these
      patients. Conversely, older patients do not view their age as an important reason
      for refusing trials. CONCLUSION: Specific clinical trials confined to older
      patients should be conducted to evaluate tumor biology, treatment tolerability,
      and the effect of comorbid conditions. Protocol designs need to stratify for age
      and be less restrictive with respect to exclusions on functional status,
      comorbidity, and previous cancers, such that results are generalizable to older
      patients. Physician education to dispel unfounded perceptions, improved access to
      available clinical trials, and provision of personnel and resources to
      accommodate the unique requirements of an older population are possible solutions
      to remove the barriers of ageism.

PMID- 15860873
TI  - Plasma cell problems: Case 1. Disseminated cutaneous plasmacytomas treated with
      total skin electron radiotherapy.

PMID- 15860872
TI  - Treatment of advanced non-small-cell lung cancer in the elderly: results of an
      international expert panel.
AB  - The best treatment for elderly patients with advanced non-small-cell lung cancer
      (NSCLC) is still debated. To guide clinical management of these patients and
      suggest the priorities for clinical research in this field, an International
      Expert Panel met in Naples, Italy, on April 19 to 20, 2004. Results and
      conclusions based on a review of evidence available in the literature to date are
      presented in this article. A comprehensive geriatric assessment is recommended to
      better define prognosis and to predict tolerance to treatment. In the first
      randomized study dedicated to elderly NSCLC patients, single-agent vinorelbine
      showed superiority over supportive care alone, both in terms of survival and
      quality of life. In a large randomized trial, gemcitabine plus vinorelbine failed
      to show any advantage over either agent alone. Subset analyses suggest that the
      efficacy of platinum-based combination chemotherapy is similar in fit older and
      younger patients, with an acceptable increase in toxicity for elderly patients.
      These data should be interpreted cautiously because retrospective subgroup
      analyses are encumbered by selection bias; hence, randomized trials dedicated to
      platinum-based chemotherapy for nonselected elderly patients are warranted.
      Several promising biologic therapies are under investigation; however, with
      present data, target-based agents as first-line treatment for elderly NSCLC
      patients are not yet recommended. Clinical research, with trials specifically
      designed for elderly patients, is mandatory. With the current evidence, single
      agent chemotherapy with a third-generation drug (vinorelbine, gemcitabine, a
      taxane) should be the recommended option for nonselected elderly patients with
      advanced NSCLC. Platinum-based chemotherapy is a viable option for fit patients
      with adequate organ function. Best supportive care remains important, in addition
      to chemotherapy or as the exclusive option for patients who are unsuitable for
      more aggressive treatment.

PMID- 15860874
TI  - Plasma cell problems: Case 2. Extramedullary cardiac plasmacytoma presenting with
      cardiac tamponade.

PMID- 15860875
TI  - Plasma cell problems: Case 3. Plasmacytoma mimicking a paraganglioma of the skull
      base: diagnostic value of somatostatin receptor scintigraphy.

PMID- 15860876
TI  - Necessary collusion: prognostic communication with advanced cancer patients.

PMID- 15860877
TI  - A strategy for hope: a commentary on necessary collusion.

PMID- 15860878
TI  - Is collusion necessary? A commentary on necessary collusion.

PMID- 15860880
TI  - Treatment of brain metastases from melanoma.

PMID- 15860881
TI  - Treatment of Wilms tumor: an international perspective.

PMID- 15860883
TI  - p53 Expression as a prognostic indicator in Hodgkin's lymphoma.

PMID- 15860886
TI  - Mammaglobin remains a useful marker for the detection of breast cancer cells in
      peripheral blood.

PMID- 15860887
TI  - Chemoradiotherapy for localized non-Hodgkin's lymphoma: lessons from old studies.

PMID- 15860891
TI  - Genetic cancer risk assessment in the newly diagnosed breast cancer patient is
      useful and possible in practice.

PMID- 15860889
TI  - Reproducibility of a semiquantitative measurement of circulating DNA in plasma
      from neoplastic patients.

PMID- 15860893
TI  - No evidence for correlation of DDX1 gene amplification with improved survival
      probability in patients with MYCN-amplified neuroblastomas.

PMID- 15860895
TI  - Use of radiolabeled bombesin in humans.

PMID- 15860896
TI  - Safety of exemestane in the Intergroup Exemestane Study.

PMID- 15860900
TI  - Comparison of the Rapid Entire Body Assessment and the New Zealand Manual
      Handling 'Hazard Control Record', for assessment of manual handling hazards in
      the supermarket industry.
AB  - This is a case study comparing the use of two different assessment tools (Rapid
      Entire Body Assessment versus New Zealand Manual Handling Hazard Control Record)
      to assess, plan and implement changes in manual handling practices in the
      supermarket industry. Existing manual handling practices being used within these
      supermarkets were assessed using each of these tools. The most hazardous tasks
      were revised to improve work methods and reviewed again using both tools, to
      determine the usefulness and effectiveness of these tools. The process generated
      considerable discussion regarding the benefits and drawbacks of each tool. The
      usefulness of each tool appears dependant on the reason for assessment and the
      anticipated outcome. REBA may be more useful if specific ergonomic or
      biomechanical changes are being implemented to decrease risk of work-related
      injury (particularly if an objective numeric score is required for re-assessment
      following modifications, to determine their effectiveness). The New Zealand Code
      of Practice for Manual Handling 'Hazard Control Record' Risk Score analysis
      process lacks specificity and objectivity, however it is less reductionistic and
      takes into account many factors other than biomechanics and ergonomics. It
      directs the user toward implementing controls, which are thorough, multi
      factorial and useful to control hazards relating to several other areas,
      including task, load, environment, people and management factors.

PMID- 15860899
TI  - The etiology of low back pain in military helicopter aviators: prevention and
      treatment.
AB  - Low back pain (LPB) is a major health problem among military rotary-wing aircrews
      worldwide. In order to define the etiology and propose remedies to LBP in
      helicopter aviators a review and critique of the literature was conducted. In
      flight sitting posture and vibration generated by the aircraft were identified as
      high risk factors for LBP. Consequently, researchers recommended ergonomic
      modifications to the crew stations. The efficacy of these technical interventions
      has not been proven. As well, these design changes are not financially practical.
      Following an in depth kinesiological analysis of the physical demands of this
      type of flying, and preliminary experimentation, an alternative aeromedical
      approach focusing on the aircrew rather than the craft is presented. The authors
      propose a set of flight-specific exercises that might effectively deal with this
      problem. A thorough testing of this approach is envisioned.

PMID- 15860901
TI  - Vocational rehabilitation policies and programmes: what can we learn from other
      countries?

PMID- 15860902
TI  - Employee occupational stress in banking.
AB  - Occupational stress literature emphasizes the importance of assessment and
      management of work related stress. The recognition of the harmful physical and
      psychological effects of stress on both individuals and organizations is widely
      studied in many parts of the world. However, in other regions such research is
      only at the introductory stages. The present study examines occupational stress
      of employees in the banking sector. A sample of 60 bank employees at different
      organizational levels and educational backgrounds was used. Data collection
      utilized the Occupational Stress Indicator (OSI). Results of data analysis
      provided evidence that employees' educational levels affect the degree of stress
      they experience in various ways. Bank employees cannot afford the time to relax
      and "wind down" when they are faced with work variety, discrimination,
      favoritism, delegation and conflicting tasks. The study also shows the degree to
      which some employees tend to bring work-related problems home (and take family
      problems to work) depends on their educational background, the strength of the
      employees' family support, and the amount of time available for them to relax.
      Finally, the drinking habits (alcohol) of the employees were found to play a
      significant role in determining the levels of occupational stress.

PMID- 15860903
TI  - A longitudinal study of the learning and retention of task-specific training.
AB  - This longitudinal study evaluated the learning and retention of task-specific
      training during the subjects' classroom performance of a one-person pivot
      transfer. Twelve subjects were videotaped completing the transfer (pretest). The
      subjects then participated in a two-hour training session. One week later
      (posttest 1), and one year later (posttest 2) the subjects were videotaped again.
      A checklist was used to analyze the videotapes. A one-way ANOVA with repeated
      measures revealed that there was a statistically significant difference between
      the tests (F = 243.73, p-value < 0.0001). A post hoc analysis (Bonferroni
      procedure) indicated that the posttest 1 scores (mean = 13, SD = 0.40) were
      significantly higher than the pretest scores (mean = 2.96, SD = 0.39) indicating
      an improved score on the checklist. There was no significant difference between
      the scores of posttest 1 and posttest 2 (mean = 12.79, SD = 0.60) indicating that
      subjects continued to perform the task with proper body mechanics one year post
      training.

PMID- 15860904
TI  - Does continuous passive motion during keyboarding affect hand blood flow and
      wrist function? A prospective case report.
AB  - The purpose of this prospective case report was to evaluate the use of a keyboard
      platform device that uses continuous passive motion (CPM) on vascular flow to the
      hand for clerical employees who perform daily keyboarding tasks. Subjects were
      two female volunteers, one symptomatic of carpal tunnel syndrome (CTS), who were
      employed in clerical positions and perform daily keyboarding tasks for most of
      their workday. Data collection consisted of baseline and follow-up measurements
      at 6 weeks, including: 1) screening for symptoms based on the Carpal Tunnel
      Function Disability Form, 2) evaluation using standard physical therapy
      examination and assessment techniques, including modified Semmes- Weinstein
      monofilament testing, 3) a typing productivity test, and 4) Doppler ultrasound
      examination to quantify vascular flow at the wrist. Results revealed that both
      subjects demonstrated an overall increase in both radial and ulnar blood flow
      velocity with no decrement in typing productivity. The symptomatic subject also
      demonstrated an overall improvement of 10 wpm in the typing tests, a decrease in
      her disability score and symptom severity, and improvement in function. Results
      suggest that use of CPM as a non-intrusive ergonomic intervention may be used to
      treat, as well as prevent, carpal tunnel-like symptoms in those who keyboard.

PMID- 15860905
TI  - Item validity of the physical demands from the Dictionary of Occupational Titles
      for functional capacity evaluation of clients with chronic back pain.
AB  - This study assessed the item validity of 15 of the physical demands from the
      Dictionary of Occupational Titles (DOT), as evaluated in a new approach to
      functional capacity evaluation (FCE) for clients with chronic back pain, the
      Gibson Approach to FCE (GAPP FCE). Fifty-two occupational therapists were sent
      the specifications of the items in the GAPP FCE procedures and were asked to rate
      the items in terms of item-objective congruence, relevance and difficulty. A
      response rate of 59.2% was obtained. The majority of the therapists agreed that
      most of the items were congruent with the objectives based on the definition of
      the physical demands from the DOT. The items evaluating Balancing and Pushing and
      Pulling had the lowest item-objective congruence. The evaluation of Balancing and
      the Lifting, Carrying and Pushing and Pulling of loads greater than light-medium
      weight (10-16 kg) were not considered significantly relevant. Concerns were
      raised about the difficulty and safety of the evaluation of Lifting, Carrying and
      Pushing and Pulling with clients with chronic back pain, particularly if the
      therapist evaluates the manual handling of medium to heavy loads. These results
      may have implications for other FCEs, particularly those which are based on the
      DOT, or when assessing clients with chronic back pain.

PMID- 15860906
TI  - The implementation of motor learning principles in designing prevention programs
      at work.
AB  - Occupational therapy practitioners offer services to workers in the workplace to
      prevent musculoskeletal disorders (MSDs), to help the injured worker restore
      function, and to recover capacities needed to return to the job. Despite the
      existence of some evidence about the efficacy of prevention programs, there is
      uncertainty and even disagreement among health professionals, about the outcome
      of prevention programs for people with MSDs. It is proposed that principles of
      motor learning can assist the therapist in structuring prevention programs to
      facilitate the workers learning of correct movement patterns. This paper
      discusses basic concepts of motor learning emphasizing characteristics of the
      learner, the type of task, the structure of practice and application to
      prevention programs at work settings. We present a four-stage model for
      prevention programs based on principles of both motor learning and ergonomics.
      This model coincides with the broad perspective suggested in current occupational
      therapy models which focuses on the person, the environment, the occupation and
      their effects on occupational performance.

PMID- 15860908
TI  - Occupational therapy practitioner role in the implementation of worksite
      accomodations.
AB  - Injured workers have the right to return to their job if they are able to perform
      their duties, according to the American with Disabilities Act, 1990. Occupational
      therapy practitioners employed in work hardening programs, or working as private
      consultants, have a significant role in assisting employees, employers and human
      resource personnel in determining "reasonable accommodations" to enable a
      qualified employee with a physical or mental disability to access the work force.
      This article discusses the application of accommodations in two case studies.

PMID- 15860910
TI  - Multivariate methods in rehabilitation.
AB  - The complexity of relationships between variables in a variety of rehabilitation
      settings can be appropriately addressed by the use of multivariate methods of
      statistical analysis. The purpose of this article is to describe (a) some basic
      concepts and principles of multivariate methods as well as (b) common
      misconceptions in the application of such methods. Specifically, the authors
      focus on the use of multivariate analysis of variance (MANOVA) in rehabilitation
      research and some pitfalls that rehabilitation researchers face when choosing
      between MANOVA for a set of outcome variables versus separate analyses of
      variance (ANOVAs) for each outcome variable. Examples of the use of MANOVA in
      rehabilitation research, as well as references to other multivariate methods, are
      also provided.

PMID- 15860909
TI  - Assistive technology outcomes in work settings.
AB  - Successfully documenting the outcomes of assistive technology (AT) interventions
      in the workplace benefits people with disabilities, service providers and
      agencies. However, no work related system currently exists that comprehensively
      collects the data needed to analyze such outcomes. Part of the reason for this
      absence of an outcome system is that, while the concept is simple, the process is
      complex and depends on the acquisition of data that represent many outcomes
      related variables. This article describes the exploratory work of the NIDRR
      (National Institute on Disability and Rehabilitation Research) funded ATOMS
      Project (Assistive Technology Outcomes Measurement System) and its efforts to
      identify existing data that might be used as the basis for an outcomes
      measurement system. Sample records from four assistive technology service
      programs were acquired and evaluated for the data they housed. This study
      discovered that AT service programs fail to collect consistent or sufficient data
      for outcomes analysis. However, discussions with AT programs that provided
      services to State vocational rehabilitation agencies revealed an interesting
      potential. Assistive technology service data in combination with data collected
      by State vocational rehabilitation departments might coalesce the needed data.
      The Federal Rehabilitation Services Administration (RSA) 911 Report aggregates
      many variables of outcomes related information including employment status and
      the success of the vocational rehabilitation investment. This combined database
      could answer a range of assistive technology outcomes related questions of
      interest to service providers, people with disabilities, and vocational
      rehabilitation State agencies. This paper describes the data needed in an
      outcomes system, reviews the data that appear to be available today related to AT
      outcomes, and projects how data from two diverse programs might be used together
      to create a significant outcomes database.

PMID- 15860911
TI  - Physical training decreases total plasma homocysteine and cysteine in middle-aged
      subjects.
AB  - AIMS: The aim of this study was to evaluate whether endurance exercise in middle
      aged men induces changes in plasma total homocysteine (tHcy) and total cysteine
      (tCys), and whether these changes depend on the diet especially on vitamin B(6),
      folic acid and vitamin B(12) intakes. METHODS: Twelve trained subjects (52.33 +/-
      2.4 years) and twelve untrained subjects (56.23 +/- 0.9 years) volunteered for
      the present study. tHcy and tCys were measured with high-pressure liquid
      chromatography at rest in both groups and during an incremental exercise
      performed on a cycle ergometer until exhaustion in the trained subjects. RESULTS:
      At baseline homocysteinemia and cysteinemia were lower in trained subjects (7.48
      +/- 0.4 and 183.45 +/- 13.6 micromol/l) compared with untrained subjects (9.79 +/
      0.4 micromol/l, p < 0.001; 229.01 +/-14.7 micromol/l, p < 0.05, respectively).
      Incremental exercise also induced a decrease in tHcy and tCys concentrations.
      Moreover, tHcy concentration was negatively related to the folic acid and B(12)
      intakes in untrained (r = -0.589, p < 0.05; r = -0.580, p < 0.05, respectively)
      as well as in trained groups (r = -0.709, p < 0.01; r = -0.731, p < 0.01,
      respectively) whereas no correlation between tCys and vitamin in the diet was
      observed. CONCLUSION: This study demonstrates that the combined effects of a
      chronic physical exercise and a high folate and vitamin B(12) intake could be
      responsible for the reduction of plasma tHcy and tCys concentrations that might
      be a key for the prevention of many diseases.

PMID- 15860912
TI  - Effect of hyperprotidic diet associated or not with hypercalcic diet on calcium
      oxalate stone formation in rat.
AB  - The aim of this study was to determine whether protein, administered alone or
      simultaneously with a hypercalcic diet, was able to aggravate calcium oxalate
      stone formation in rats. Thirty-two male Wistar rats were randomly divided into
      four groups of 8 rats each and assigned a calcium oxalate lithogenic diet added
      to their drinking water for 3 weeks. One group, used as reference, received a
      standard diet prepared in our laboratory. The second was assigned the same diet
      but supplemented with 7.5 g animal proteins/100 g diet. The third received a diet
      containing 500 mg calcium more than the standard group. The diet given to the
      last group was supplemented with calcium and protein at the same doses indicated
      previously. One day before the end of treatment, each animal was placed in a
      metabolic cage to collect 24-hour urine samples and determine urinary creatinine,
      urea, calcium, magnesium, phosphate, uric acid, citric acid and oxalate levels.
      Immediately thereafter, aortic blood was collected to determine the same
      parameters as in urine. The kidneys were also removed to determine calcium
      oxalate deposits. Our results showed an increased 24-hour urinary excretion of
      calcium, oxalate and uric acid and decreased urinary citric acid excretion only
      in groups that received protein supplementation. At the same time, calcium
      oxalate deposits were found significantly higher in hyperprotidic diets than
      reference or calcium-supplemented groups. According to these findings, glomerular
      filtration, fractional excretion of urea and reabsorption of water, calcium and
      magnesium were found significantly lower in hyperprotidic diets compared to other
      groups. These results demonstrate that proteins could seriously aggravate calcium
      oxalate stones and cause renal disturbances.

PMID- 15860913
TI  - Biophysical and physiological properties of porcine surfactant enriched with
      polymyxin B.
AB  - OBJECTIVE: We examined whether the biophysical and physiological properties of
      Curosurf were improved by the cyclic amphipathic decapeptide polymyxin B (PxB).
      METHODS: Curosurf was diluted to 1-5 mg/ml with PxB added at 1, 2 or 3% (w/w).
      Albumin was added at 40 mg/ml. Minimum surface tension (gammamin) during surface
      compression was determined for each mixture with pulsating bubble. Immature
      newborn rabbits were treated with 2.5 ml/kg of Curosurf 80 mg/ml, or Curosurf 32
      mg/ml with or without 2% PxB and ventilated for up to 5 h. RESULTS: At surfactant
      concentration 2 mg/ml, gammamin was high (17 +/- 8.9 mN/m) but remained low (2.7
      +/- 0.8 mN/m) when PxB was added. Albumin inactivated Curosurf at both 2 and 3.5
      mg/ml; this inactivation was prevented by 2% PxB. Treatment of newborn rabbits
      with Curosurf 80 mg/kg + 2% PxB significantly decreased incidence of pneumothorax
      in comparison with controls but had no significant effect on lung-thorax
      compliance or alveolar expansion. CONCLUSION: Addition of 2% PxB improves surface
      activity of Curosurf at low concentration, increases its resistance to
      inactivation by albumin, and reduces the incidence of pneumothorax in immature
      newborn rabbits undergoing prolonged ventilation.

PMID- 15860914
TI  - Early supported discharge for stroke patients improves clinical outcome. Does it
      also reduce use of health services and costs? One-year follow-up of a randomized
      controlled trial.
AB  - BACKGROUND: An early supported discharge service (ESD) appears to be a promising
      alternative to conventional care. The aim of this trial was to compare the use of
      health services and costs with traditional stroke care during a one-year follow
      up. METHODS: Three hundred and twenty patients were randomly allocated either to
      ordinary stroke unit care or stroke unit care combined with ESD which was
      coordinated by a mobile team. The use of all health services was recorded
      prospectively; its costs were measured as service costs and represent a
      combination of calculated average costs and tariffs. Hospital expenses were
      measured as costs per inpatient day and adjusted for the DRG. RESULTS: There was
      a reduction in average number of inpatient days at 52 weeks in favour of the ESD
      group (p = 0.012), and a non-significant reduction in total mean service costs in
      the ESD group (EUR 18,937/EUR 21,824). ESD service seems to be most cost
      effective for patients with a moderate stroke. CONCLUSION: Acute stroke unit care
      combined with an ESD programme may reduce the length of institutional stay
      without increasing the costs of outpatient rehabilitation compared with
      traditional stroke care.

PMID- 15860915
TI  - The Klumpke family--memories by Doctor Dejerine, born Augusta Klumpke.
AB  - In this paper, we present a translation of an unpublished autobiographical
      document by Augusta Dejerine-Klumpke, reporting her early years before she came
      to Paris to study medicine, when she was able to become one of the first women in
      France to hold a hospital position, as an extern and an intern. This American
      born girl later married Jules Dejerine, who was to become the second successor to
      Charcot at La Salpetriere 23 years later. The present document gives a vivid
      account on the preceding years, and emphasizes the extraordinary dynamism and
      enthusiasm of a young woman, whose efforts and contributions influenced neurology
      at the turn of the 20th century, and dramatically changed the role of women in
      medical careers.

PMID- 15860917
TI  - Epidemiology of multiple sclerosis in Kuwait: new trends in incidence and
      prevalence.
AB  - The epidemiology of multiple sclerosis (MS) is undergoing dramatic changes; MS is
      occurring with increased frequency in many parts of the world. In this
      retrospective study, we examined the changes in incidence and prevalence of MS in
      Kuwait in the period between 1993 and 2000. We analyzed the records of patients
      with clinically defined and laboratory supported MS. The total incidence rate
      increased from 1.05/100,000 population in 1993 to 2.62/100,000 in 2000. The
      increased incidence of MS was most pronounced among Kuwaiti women (from
      2.26/100,000 in 1993 to 7.79/100,000 in 2000. The total prevalence rate increased
      from 6.68/100,000 in 1993 to 14.77/100,000 in 2000. It was much higher for
      Kuwaitis (31.15/100,000), as compared to non-Kuwaitis (5.55/ 100,000), in a
      complete reversal of the pattern observed before 1990. The prevalence was also
      higher among Kuwaiti women (35.54/100,000), as compared with Kuwaiti men
      (26.65/100,000). In conclusion, the incidence and prevalence of MS in Kuwait has
      increased between the early and late 1990s with no signs of leveling off. In a
      geographic area that was previously associated with low prevalence, local
      environmental factors may be responsible for these dramatic changes.

PMID- 15860916
TI  - Mitochondrial DNA variants in a portuguese population of patients with
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disorder associated
      with dementia in late adulthood. Mitochondrial respiratory chain impairment has
      been detected in the brain, muscle, fibroblasts and platelets of AD patients,
      indicating a possible involvement of mitochondrial DNA (mtDNA) in the etiology of
      the disease. Several reports have identified mtDNA mutations in AD patients, but
      there is no consensual opinion regarding the cause of the impairment. We have
      studied mtDNA NADH dehydrogenase subunit 1 nucleotides 3337-3340, searching for
      mutations. Our study group included 129 AD patients and 125 healthy age-matched
      controls. We have found alterations in two AD patients: one had two already known
      mtDNA modifications (3197 T-C and 3338 T-C) and the other a novel transition
      (3199 T-C) which, to our knowledge, has not been described before.

PMID- 15860918
TI  - Is the measurement of cerebral microembolic signals a good surrogate marker for
      evaluating the efficacy of antiplatelet agents in the prevention of stroke?
AB  - Stroke is difficult to treat with few treatment options. Until such time as
      appropriate therapeutic regimens are established, prevention, both in the primary
      and in the secondary setting, is of paramount importance. Evaluation of
      pharmacological agents for the prevention of stroke in conventional clinical
      studies has the advantage that the outcome parameter is a direct measure of
      efficacy, and the disadvantage that many patients must be recruited and many
      evaluations performed over an extended period to provide adequate statistical
      power, making such studies lengthy and costly. Measurement of cerebral
      microembolic signals (MES) using transcranial Doppler ultrasonography has been
      proposed as a useful surrogate end point to investigate new antiplatelet agents
      and to evaluate further the benefits of existing antiplatelet therapies. MES
      measurements may provide a means of more directly evaluating the pharmacological
      activity of an antiplatelet agent. However, does measurement of MES accurately
      predict efficacy in stroke prevention? This review evaluates recent studies where
      the relationship between MES and cerebral ischaemic events has been explored and
      studies where the effects of antiplatelet agents on MES rates have been
      investigated. Overall, there is a growing body of evidence to suggest that MES
      may be used as a surrogate marker for cerebral infarction and clinical events,
      thus allowing quick appraisal of the efficacy of antiplatelet agents. Studies
      currently in progress should provide further insight into the value of the
      measurement of MES in clinical studies in stroke prevention.

PMID- 15860920
TI  - Accelerated bone turnover in pregnant women with McCune-Albright syndrome.
AB  - Bone turnover in pregnant women with McCune-Albright syndrome may be affected by
      both the syndrome and pregnancy. This study evaluated changes in biochemical bone
      turnover markers in pregnant women with the syndrome. Serum calcium, phosphorus,
      1,25-dihydroxyvitamin D (1,25-(OH)2D), intact osteocalcin (I-OC) and alkaline
      phosphatase (ALP), and urinary pyridinoline (Pyr), deoxypyridinoline (D-Pyr) and
      hydroxyproline (HPR) were measured during pregnancy and postpartum in 2 women
      with McCune-Albright syndrome. Serum calcitonin (CT), and plasma intact
      parathyroid hormone (I-PTH) and parathyroid hormone-related protein (PTHrP) were
      also measured in 1 patient. Serum corrected Ca levels were normal or low-normal;
      phosphorus levels were normal, and 1,25-(OH)2D levels increased toward term and
      decreased thereafter, similar to normal pregnant women. Urinary Pyr, D-Pyr and
      HPR were elevated during pregnancy compared to normal pregnant women, peaked just
      after delivery, and decreased thereafter. Serum I-OC and ALP levels were high
      during pregnancy and postpartum. Intact PTH levels were increased during
      pregnancy and postpartum compared to normal pregnant women, whereas serum CT and
      PTHrP levels were not elevated. Both bone formation and absorption appear to be
      more enhanced during pregnancy and postpartum in women with McCune-Albright
      syndrome than in normal pregnant women. Additional or amplified cyclic AMP
      synthesis in bone cells through activation of the alpha subunit of G protein,
      independent of hormonal control, may explain the high local bone turnover.

PMID- 15860919
TI  - Huge spindle cell hemangioma of the cervix--mimicking a pelvic tumor.
AB  - BACKGROUND: Spindle cell hemangiomas are rare vascular tumors characterized by
      cavernous blood vessels and spindled areas reminiscent of Kaposi's sarcoma.
      Cervical hemangiomas are rare, and the spindle cell subtype is rarer still. CASE:
      Examination of a 39-year-old patient presenting with pelvic pain revealed a
      remarkable pelvic mass consisting of a 10-cm tumor extending from the cervix to
      the retroperitoneum. The pathology report demonstrated spindle cell hemangioma.
      CONCLUSION: This is a rare case of spindle cell hemangioma of the cervix resected
      transvaginally.

PMID- 15860922
TI  - Identification of novel mutations of the DAX-1 gene in patients with X-linked
      adrenal hypoplasia congenita.
AB  - OBJECTIVE: X-linked adrenal hypoplasia congenita (AHC) is a condition clinically
      featuring adrenal insufficiency and hypogonadotropic hypogonadism caused by
      mutations of DAX-1. This study was undertaken to characterize the molecular
      defects of DAX-1 in 3 unrelated Korean patients with AHC. PATIENTS AND METHODS:
      Patient 1 is a 6-year-old boy who presented with a salt-losing adrenal crisis in
      the neonatal period. Patient 2 is a 3-year-old boy who manifested aspiration
      pneumonia and adrenal insufficiency at the age of 1 month. Patient 3 is a 7-year
      old boy who developed an adrenal crisis at the age of 3 days. In each of these
      patients, DAX-1 was analyzed by direct DNA sequencing after polymerase chain
      reaction amplification of the entire coding region. RESULTS: Direct sequencing of
      DAX-1 revealed two novel mutations, 1156_1157delCT in patient 1 and another novel
      nonsense mutation W105X in patient 2. Patient 3 had complete deletion of DAX-1.
      In patient 3, serum transaminases and creatine kinase levels were elevated while
      the glycerol kinase activity of leukocytes was decreased. Markedly elevated
      glycerol excretion was detected by urine organic acid analysis. Patient 3 was
      diagnosed as Xp21 contiguous gene syndrome associated with deletions of the
      entire IL1RAPL, GK genes and the C-terminal region of DMD gene. CONCLUSIONS: Two
      novel mutations of DAX-1 were detected in 2 unrelated patients with AHC, and
      complete deletion of DAX-1 in a patient with Xp21 contiguous gene syndrome who
      also presented with glycerol kinase deficiency, Duchenne muscular dystrophy, and
      AHC.

PMID- 15860924
TI  - Influence of epoietinum therapy on the oxidative stress in haemodialysis
      patients.
AB  - BACKGROUND: The causes of oxidative stress in haemodialysis (HD) patients are
      still controversial. Beside the uraemic state and dialysis-related factors,
      adjuvant drug therapies such as epoietinum (rHuEpo) and intravenous iron were
      involved. METHODS: Several parameters related to oxidative stress were assessed
      by spectrophotometry in stable HD patients, treated for at least 2 months with
      epoietinum (n = 14; mean dose = 97.7 +/- 19.1 U/kg/week) or not (n = 15), none of
      them on iron therapy, and in 13 controls. Plasma thiobarbituric acid-reactive
      substances (TBARS) were used as markers of reactive species generation.
      Erythrocyte and plasma antioxidant systems, reflected by non-protein erythrocyte
      thiols, and erythrocyte enzyme activities -- superoxide dismutase (SOD),
      glutathione peroxidase, catalase and plasma total thiols, respectively -- were
      also investigated. RESULTS: There were no differences between HD subgroups
      regarding haemoglobin levels. Plasma TBARS was increased in all HD patients as
      opposed to controls, irrespective of rHuEpo therapy. In addition, no change in
      antioxidant status parameters between rHuEpo-treated and -untreated patients was
      observed. Except for SOD, the other antioxidant indices were higher in all HD
      patients versus controls. CONCLUSIONS: These results suggest that (1) chronic HD
      patients appear to have simultaneously enhanced reactive species generation and
      antioxidative systems efficiency, and (2) epoietinum therapy did not change their
      oxidative status, at least in the absence of concomitant iron supplementation and
      at similar haemoglobin levels.

PMID- 15860923
TI  - Elastic lamina defects are an early feature of aortic lesions in the
      apolipoprotein E knockout mouse.
AB  - The aortae from male apolipoprotein E knockout (apoE-/-) mice were examined by
      serial section immunohistochemistry and electron microscopy to determine the
      continuity of the internal elastic lamina (IEL) and its association with
      developing intimal lesions. While in this model, defects in the elastic laminae
      have previously been described beneath advanced xanthomatous lesions, this study
      demonstrates that disruption of the IEL may be a primary factor in the
      localization and pathogenesis of intimal lesions in the apoE-/- mouse. IEL
      defects were found beneath early lesions in animals as young as 8 weeks of age.
      Small defects without associated intimal alteration were also observed. The
      elastic tissue defects beneath early intimal lesions were usually transversely
      orientated with abrupt "break" edges. Regions consistent with direct enzymatic
      digestion of the IEL were relatively rare and only observed beneath advanced
      plaques, particularly in the brachiocephalic artery. The presence of IEL defects
      around branch sites of old C57BL/6J control mice along with their matching
      localization and morphology in apoE-/- appears consistent with biomechanical
      fatigue rather than direct enzymatic degradation. In conclusion, disruption of
      the IEL appears to be a prominent early, if not initial, feature of the apoE-/-
      model of atherosclerosis and may act as the nidus upon which intimal lesions
      develop.

PMID- 15860921
TI  - Is steroid therapy needed in the treatment of destructive thyrotoxicosis induced
      by alpha-interferon in chronic hepatitis C?
AB  - OBJECTIVE: Treatment with interferon (IFN) of patients affected by chronic
      hepatitis C (CH-C) may produce alterations in thyroid function, such as
      hypothyroidism, Graves'-like hyperthyroidism and destructive thyrotoxicosis (DT).
      IFN-induced DT is characterized by suppressed serum TSH levels, normal or
      elevated FT4 and FT3 concentrations, with the presence or absence of thyroid
      peroxidase antibodies and antithyroglobulin antibodies, the absence of thyroid
      receptor antibodies and radioactive iodine uptake suppressed or <5%. DESIGN: IFN
      induced DT is a mild clinical disease, because thyroid-destructive processes last
      for a short time and involve a small portion of the gland. At present, the
      therapeutic approach in DT suggests IFN withdrawal and 1-2 months of
      methylprednisolone treatment. METHODS: In consideration of possible untoward side
      effects of steroid treatment in patients with CH-C, we studied two groups of
      patients with CH-C who developed DT after treatments with various preparations of
      recombinant IFN (with or without ribavirin). Patients sequentially entered the
      study during a 4-year period, at the time of DT diagnosis, when IFN therapy was
      discontinued. The first 12 subjects (group A) were treated with 8-16 mg/day
      methylprednisolone for 30-40 days after IFN withdrawal; in the following 15
      patients (group B), IFN withdrawal was not followed by any additional treatment.
      All patients underwent clinical and laboratory controls of thyroid function at 1,
      2, 3 and 6 months after DT diagnosis. RESULTS: The results showed restoration of
      euthyroidism in both group A and group B patients at 6 months after DT diagnosis,
      regardless of steroid treatment. CONCLUSIONS: The simple withdrawal of IFN
      therapy in patients with CH-C, who had developed DT, appears to be effective in
      the treatment of the thyroid disease. This therapeutic approach should be
      preferred in order to avoid possible undesired side effects of steroid therapy in
      patients with CH-C.

PMID- 15860926
TI  - Transcriptional activation of nucleus tractus solitarii/area postrema
      catecholaminergic neurons by pharmacological inhibition of caudal hindbrain
      monocarboxylate transporter function.
AB  - Evidence that intracerebral lactate administration alters electrophysiological
      sensitivity of metabolic-signaling neurons and hypoglycemic counterregulation
      suggests that this substrate fuel is a monitored indicator of in central nervous
      system energy balance. Catecholaminergic (CA) neurons in the caudal hindbrain
      nucleus tractus solitarii (NTS)/area postrema (AP) complex participate in the
      origin and/or relay of stimuli that signal deficient glucose provision to the
      brain. The present studies evaluated the responsiveness of this neurochemical
      phenotype to lactate insufficiency by investigating the effects of
      pharmacological inhibition of local monocarboxylate transporter activity on the
      transcriptional status of these cells. Adult female rats were sacrificed by
      transcardial perfusion 2 h after infusion of graded doses of the monocarboxylate
      transporter inhibitor, alpha-cyano-4-hydroxycinnamic acid (4-CIN), or vehicle
      into the caudal fourth ventricle, and tissue sections through the NTS/AP were
      processed by dual-label immunofluorescence histochemistry for demonstration of
      cytoplasmic tyrosine hydroxylase (TH) and the inducible nuclear AP-1 regulatory
      factor, Fos. While vehicle administration resulted in negligible Fos
      immunostaining within the NTS, 4-CIN-treated animals exhibited dose-dependent
      increases in mean numbers of Fos-ir- and TH-/Fos-ir-positive neurons in this
      structure. These data show that pharmacological suppression of lactate
      trafficking in the caudal hindbrain elicits the genomic activation of NTS/AP CA
      neurons. In light of evidence implicating this neurochemical phenotype in
      signaling of cellular energy imbalance, the current results support the view that
      diminished uptake and/or catabolism of lactate may underlie CA neuronal
      activation of neural pathways governing compensatory behavioral and physiological
      responses to metabolic substrate deficiency.

PMID- 15860925
TI  - Adrenocorticotropin/cortisol and arginine-vasopressin secretory patterns in
      response to ghrelin in normal men.
AB  - This study was performed in order to establish the secretory patterns and the
      possible relationships between the adrenocorticotropin (ACTH)/cortisol and
      arginine vasopressin (AVP) responses in normal men to the systemic administration
      of ghrelin, an endogenous ligand for the growth hormone secretagogue receptor.
      For this purpose, a bolus of 1 microg/kg ghrelin was injected intravenously in 9
      normal men. AVP, ACTH and cortisol significantly rose in response to ghrelin
      injection; however, in all subjects the AVP rise preceded the ACTH/cortisol
      responses. In fact, the mean peak levels of AVP, ACTH and cortisol after ghrelin
      injection were observed at 15, 30 and 45 min, respectively. When peak AVP
      responses to ghrelin were considered together with ACTH and cortisol peak levels,
      highly significant positive correlations were observed (AVP and ACTH, r = 0.94, p
      < 0.001; AVP and cortisol, r = 0.92, p < 0.001). In conclusion, this study shows
      that the AVP response to ghrelin precedes the concomitant ACTH/cortisol rise and
      that these hormonal responses are highly positively correlated. These
      observations support the hypothesis that AVP mediates ghrelin-induced ACTH
      secretion in normal men.

PMID- 15860927
TI  - Myosin loss in denervated rat soleus muscle after dexamethasone treatment.
AB  - OBJECTIVE: Critical illness myopathy (CIM) is an acute myopathy that appears in
      the setting of critical illness or during exposure to corticosteroids and
      neuromuscular blocking agents. Its pathological feature is selective loss of
      thick myosin filaments. Our aim is to gain further insight into the
      pathomechanism of myosin loss in this myopathy. METHODS: To clarify the
      expression of myosin heavy chain (MHC) and ubiquitin ligase atrogin-1 in this
      myopathy, histological, immunohistochemical, SDS-PAGE, and semiquantitative
      reverse transcriptase-polymerase chain reaction studies were performed on
      innervated and denervated rat soleus muscles after saline and dexamethasone
      treatments. RESULTS: Denervated muscles from dexamethasone-treated rats showed
      marked MHC loss. The mRNA expression of ubiquitin ligase atrogin-1 was
      significantly increased in denervated dexamethasone-treated muscles, suggesting
      that the ubiquitin-proteasome pathway plays an important role in muscular wasting
      in CIM. Furthermore, mRNA levels of MHC I, a myosin isoform, were decreased in
      the denervated dexamethasone-treated muscles. CONCLUSION: Our findings suggest
      that an altered transcription rate of myosin, as well as the upregulation of
      multiple ubiquitin ligases, may be responsible for selective myosin loss in this
      myopathy.

PMID- 15860928
TI  - Glycyrrhizin inhibits R5 HIV replication in peripheral blood monocytes treated
      with 1-methyladenosine.
AB  - R5 HIV replicated in freshly isolated human peripheral blood monocytes after
      treatment with 1-methyladenosine (fresh PBM/MA), an immunosuppressive compound
      isolated from tumorous ascites fluids, while viral replication was not
      demonstrated in untreated peripheral blood monocytes (fresh PBM). The R5 HIV
      replication in fresh PBM/MA was inhibited by glycyrrhizin (GL). Without any other
      stimulation, fresh PBM/MA produced CCL2 and IL-10, while these soluble factors
      were not released from fresh PBM. GL greatly inhibited the production of CCL2 and
      IL-10 in fresh PBM/MA. After treatment with CCL2 and/or IL-10, CCR5 mRNA
      expression in fresh PBM was markedly enhanced, while only a trace level of the
      mRNA expression was detected in these cells in the absence of CCL2 or IL-10. CCR5
      mRNA expression in fresh PBM treated with CCL2 or IL-10 was clearly inhibited by
      GL. These results indicate that GL inhibits R5 HIV replication in fresh PBM/MA
      through the inhibiting CCR5 expression mediated by CCL2 or IL-10.

PMID- 15860929
TI  - Cytochemical analysis of pancreatic islet lipoapoptosis: hyperlipidemia-induced
      cytoinvolution following expression of the diabetes (db/db) mutation.
AB  - The diabetes (db/db) genotype mutation induces a hyperglycemic-hyperinsulinemic
      endometabolic state in C57BL/KsJ mice, manifesting a type II NIDDM diabetes
      obesity syndrome (DOS) associated with intrinsic leptin receptor expression
      defects. The severity of the DOS-induced premature pancreatic dysfunction and
      cytoatrophic involution has been linked to the severity of hypercytolipidemia
      which develops in pancreatic islets following systemic lipoidosis. The current
      studies define the cytochemical changes associated with pancreatic islet and
      acinar vesicular degranulation (deproteinization), cytoinvolution and B-cell
      dysfunction relative to the onset of cellular (nuclear DNA fragmentation)
      apoptosis in 20- to 26-week-old chronic db/db mutants relative to control (+/?)
      indices. The db/db mutation induced dramatic increases in body weights, blood
      glucose as well as serum and tissue triglyceride concentrations relative to +/?
      parameters. In contrast, pancreatic tissue weights and insulin concentrations
      were significantly decreased in db/db groups in association with premature islet
      cytoatrophy relative to +/? indices. Concurrent elevations in db/db tissue
      triglyceride concentrations and islet cytolipid depositions accompanied the
      progressive pancreatic cytoatrophic alterations. Diminished B-cell vesicular
      (insulin) granulation was pronounced in atrophic pancreatic islets, which were
      also characterized by hyperplasic acinar cellular intrusion and subsequent
      proteolytic B-cell dissolution coincident with 3'-DNA fragmentation-indexed
      (TUNEL-labeled) nuclear apoptosis. The chronic expression of the db/db mutation
      exacerbated these pancreatic islet B-cell atrophy indices, characterized by
      insulin vesicular degranulation, suppressed systemic insulin concentrations,
      invasive hypercytolipidemia, progressive cellular atrophy and hyperplasic acinar
      proteolytic dissolution, culminating in islet volume/mass reduction and chronic
      db/db-related pancreatic involution. The results of these studies indicate that
      pancreatic islet B-cell apoptosis is coincident with the progressive
      hypercytolipidemia component of the type II DOS promoted by the db/db genotypic
      mutation. These data suggest that the severity of progressive pancreatic
      lipoapoptosis disrupts regulatory cellular metabolic cascades, resulting in
      nuclear fragmentation, organelle dissolution and the subsequent promotion of a
      nonhomeostatic cytochemical milieu which ultimately renders islet B-cell
      populations susceptible to acinar proteolytic dissolution and progressive
      pancreatic involution.

PMID- 15860931
TI  - The expression pattern of UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetyl
      galactosaminyl transferase-3 in squamous cell carcinoma of the esophagus.
AB  - OBJECTIVE: UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyl
      transferase-3 (GalNAc-T3) regulates the initial glycosylation of mucin-type O
      linked proteins. Although a different expression of GalNAc-T3 has been reported
      in various cancers, the expression has not been characterized in squamous cell
      carcinoma (SCC) of the esophagus. METHODS: We have also evaluated the expression
      of this enzyme in surgically resected esophageal mucosa. By immunohistochemical
      staining using a specific antibody, we evaluated the expression of GalNAc-T3 in
      66 esophageal SCC and 28 dysplasia samples, and analyzed the relationship between
      the expression of GalNAc-T3 and clinicopathological features. RESULTS: GalNAc-T3
      was positively detected in the majority of the cases of SCC, but not in dysplasia
      as well as the normal counterparts in resected esophagus. GalNAc-T3 was
      determined to be positive in 37 cases (68.5%) of differentiated carcinomas, but
      only in 4 cases (33.3%) of undifferentiated carcinomas (p < 0.05). Hematogeneous
      metastasis was observed in 13 of 41 (31.7%) GalNAc-T3-positive tumors, which was
      significantly more frequent than in negative tumors (2/25, 8%; p < 0.05). The
      number of metastatic nodes was significantly higher in tumors with GalNAc-T3
      positive than GalNAc-negative expression (4.2 +/- 3.2 vs. 2.8 +/- 1.3, p < 0.05).
      The survival rate tended to be lower for patients with GalNAc-T3-positive tumors,
      although the difference was not statistically significant (p = 0.18). CONCLUSION:
      GalNAc-T3 may play a positive role in the process of carcinogenesis and
      progression in esophageal SCC. Functional inhibition of GalNAc-T3 may be
      effective for the prevention and treatment of esophageal SCC.

PMID- 15860930
TI  - A single nucleotide polymorphism in the 5' untranslated region of the EGF gene is
      associated with occurrence and malignant progression of gastric cancer.
AB  - OBJECTIVE: Epidermal growth factor (EGF) has many biological functions and plays
      an important role in the progression of various tumors including gastric cancer.
      An A-G single nucleotide polymorphism (SNP) at position 61 in the 5'-untranslated
      region (UTR) of the EGF gene has recently been reported to be associated with
      different levels of EGF production. We examined whether this polymorphism is
      correlated with the development and malignant phenotypes of gastric cancer.
      METHODS: The study population included 200 gastric cancer patients and 230
      healthy control subjects. The SNP in the 5'-UTR of the EGF gene was analyzed by
      polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The
      A allele was significantly less frequent in patients than in controls (p = 0.01).
      Individuals with the A/A or A/G genotype showed a significantly lower risk of
      gastric cancer than those with the G/G genotype [adjusted odds ratio (OR) =
      0.56], whereas the same genotypes were associated with malignant progression of
      this cancer, e.g. deeper tumor invasion, increased lymph node metastasis and
      advanced clinical stage, and histological classification in gastric cancer
      patients (adjusted OR = 1.80, 1.98, 2.26 and 1.89, respectively). CONCLUSIONS:
      Our findings suggest that the A-G polymorphism of EGF is involved not only in the
      occurrence but also in the malignant progression of gastric cancer.

PMID- 15860937
TI  - [Exploring the nature of caring in Hwa-Byung--transpersonal Caring-Healing
      Model].
AB  - Hwa-Byung(HB) has been categorized as a Korean culture-bound syndrome that is
      prevalent in married women of low socioeconomic status. PURPOSE: The Purpose of
      the study was to search for the essence of HB and a caring-healing process of HB.
      Then the research result discusses whether the Transpersonal Caring-Healing Model
      has been congruent with it. METHOD: Case examples resulted from in-depth
      telephone counseling over a period of time at the Women's Hot Line with a client
      who is a housewife with HB. The counseling content was analyzed through Giorgi's
      method of descriptive phenomenology. RESULT: The core meaning of the essence of
      HB was 'injustice'; and essential themes were 'lack of reciprocity', 'infidelity'
      'suppressed aggression and powerlessness' and 'need for recognition'. The core
      meaning of the essence of the caring-healing process was 'caring-healing
      experience (maintaining a trust relationship)'; and essential themes were 'active
      listening', 'empathy' and 'forming a therapeutic relationship'. According to
      Watson, 'active listening', 'empathy' and 'forming a therapeutic relationship'
      were identified as intentionality, intersubjectivity and transpersonal.
      CONCLUSION: Transpersonal caring can release inner power and strength and help
      the person to gain a sense of inner harmony. Transpersonal caring is as important
      to healing as are conventional treatment approaches and even more powerful in the
      long run.

PMID- 15860932
TI  - Alteration of gene expression in intervertebral disc degeneration of passive
      cigarette- smoking rats: separate quantitation in separated nucleus pulposus and
      annulus fibrosus.
AB  - OBJECTIVE: We constructed a passive cigarette-smoking model with rats to
      investigate the molecular mechanism of intervertebral disc degeneration, and
      found by gene expression analysis that passive cigarette smoking stimulated the
      stress-responsive signal pathway and inhibited the apoptotic pathway. In this
      study, to clarify that these changes were derived from either nucleus pulposus
      (NP) or annulus fibrosus (AF), we separately collected NP and AF and
      quantitatively analyzed gene expression. METHODS: Total RNA was extracted from NP
      and AF of the lumbar intervertebral discs from rats which were kept in a smoking
      box for 4 and 8 weeks. Gene expression was measured by real-time PCR of cDNA
      synthesized from the total RNA. RESULTS: Stress-responsive protein, heat shock
      protein 70, was expressed similarly in NP and AF, and was upregulated to the same
      degree after 8 weeks of passive cigarette smoking. The protein tyrosine
      phosphatase gene was expressed more strongly in AF than in NP, and was
      upregulated after 8 weeks of smoking in both tissue parts. The type II collagen
      and aggrecan genes were predominantly expressed in AF and NP, respectively.
      CONCLUSION: These results indicate that passive cigarette smoking stimulates both
      NP and AF, and induces the stress-responsible genes such as heat shock protein 70
      and protein tyrosine phosphatase in both.

PMID- 15860936
TI  - Gamma knife radiosurgery for tumors involving the cavernous sinus.
AB  - OBJECTIVE: To study the features of diagnosis and radiosurgery of tumors
      involving the cavernous sinus. METHODS: From December 1994 to the end of 2000,
      175 patients with cavernous sinus lesions were treated by Leksell gamma knife
      (GK) in our Institute. Ninety patients (51.4%) had had open surgery previously.
      Our experience of treating cavernous sinus tumors by GK was analyzed
      retrospectively. RESULTS: A Hundred and forty-four (82.3%) patients were followed
      from 1 to 84 months (median 32.5 months); total tumor control rate was 94%.
      Surgery was performed after radiosurgery in 3 patients because of tumor
      enlargement. Metastatic tumor in the cavernous sinus was highly sensitive to
      irradiation. These lesions shrunk markedly on MRI 2-3 months after GK surgery.
      The median survival time was 12.2 months, and patients died of noncavernous sinus
      lesions. CONCLUSION: With high tumor control rate and few complications, GK
      surgery could become a main option for small benign or residual tumors involving
      the cavernous sinus. It is also very useful as part of comprehensive therapy for
      metastatic tumors in the cavernous sinus.

PMID- 15860934
TI  - Toxoplasma gondii antigens GRA1 (p24) and SAG1 (p30): a comparison of their
      stimulatory influence on T-cell activation and cytokine expression in in vitro
      cultures.
AB  - The influence of recombinant cell surface SAG1 (rp30) and secretory GRA1 (rp24)
      antigens (Ag) on T-cell activation and cytokine induction in vitro was compared.
      T-cell activity and the level of IFN-gamma, IL-10 and IL-12 expression in rp30
      immunized T cells were considerably increased in the presence of rp30 Ags. IgG2a
      and IgG1 antibodies (Ab) were detected in sera of rp24- and rp30-immunized mice,
      with the secretory rp24 Ag having induced significantly higher titer of IgG1 Ab.
      In vitro, the greater antigenicity of surface rp30 Ag was notable based on the
      level of T-cell activation, and cytokine synthesis suggestive of the
      participation of Th1 cells. Although, IFN-gamma expression by rp24 Ag was lower
      compared to rp30 Ag, the synthesis of both IgG2a and IgG1 Abs reflects the
      protective nature of rp24 Ag. We have generated two recombinant Toxoplasma gondii
      Ags that demonstrated differences in antigenicity in vitro. It would be
      interesting to evaluate the mechanism(s) of immunity induced by SAG1 (p30) and
      GRA1 (p24) Ags against infection with T. gondii in vivo.

PMID- 15860938
TI  - [Prediction model on mental health status in middle-aged women of an urban area].
AB  - PURPOSE: This study was designed to construct a structural model for explaining
      mental health status in middle-aged women. METHODS: The data was collected by
      self-reported questionnaires from 206 middle-aged women in Seoul. Data analysis
      was done with the SAS pc program for descriptive statistics and a PC-LISREL
      Program for finding the best fit model which assumes causal relationships among
      variables. RESULTS: The overall fit of the hypothetical model to the data was
      good, but paths and variables of the model were modified by considering
      theoretical implications and statistical significances of parameter estimates.
      Thus it was modified by excluding 3 paths. The modified model showed was good fit
      to the data(chi(2)=177.55, p=.00), GFI=0.908, AGFI=0.860, RMR=0.013, NFI=0.972,
      NNFI=0.982). Perceived stress, anger expression method, and self-esteem were
      found to have direct effects on mental health status in middle-aged women. These
      predictive variables of mental health status explained 66.6% of the model.
      CONCLUSION: Programs to enhance mental health status in middle-aged women should
      include stress management skill, anger expression skill, and self-esteem
      enhancement skills to be effective.

PMID- 15860935
TI  - Clinical importance of transforming growth factor-beta but not of tumor necrosis
      factor-alpha gene polymorphisms in patients with the myelodysplastic syndrome
      belonging to the refractory anemia subtype.
AB  - OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) and transforming growth
      factor-beta (TGF-beta) are cytokines that play key roles in the myelodysplastic
      syndrome (MDS). There have been several reports on the presence of genetic
      polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta1
      protein, located in codon 10 in exon 1 and in the -308 promoter region of TNF
      alpha. The objective of this study was to investigate the association between TNF
      alpha and TGF-beta1 gene polymorphisms and the susceptibility to MDS and the
      progression of the disease among patients with MDS belonging to the refractory
      anemia (RA) subtype. METHODS: The diagnosis of MDS (n = 50) was based on the FAB
      criteria. The TNF-alpha genotypes were analyzed by PCR-RFLP and the TGF-beta
      genotypes were analyzed using an amplification refractory mutation system.
      RESULTS AND CONCLUSIONS: Compared with healthy control subjects, patients with RA
      showed no significant deviations in genotype or allele frequencies of TNF-alpha.
      The TT homozygosity at codon 10 of TGF-beta1 was significantly higher among
      patients with bi- or pancytopenia (severe group) than in the patients with anemia
      only (mild group; odds ratio = 6.99, p = 0.003). These findings suggest that the
      TGF-beta1 gene polymorphism in codon 10 and the -308 TNF-alpha gene polymorphism
      do not predispose to the development of RA, but the TGF-beta1 gene polymorphism
      may affect disease progression.

PMID- 15860939
TI  - [Health status, health perception, and health promotion behaviors of low-income
      community dwelling elderly].
AB  - PURPOSE: The purpose of the study was to investigate the health status(present
      illness, ADL and IADL), health perception, and health promotion behaviors of low
      income elderly who are receiving the visiting nurse service in the community.
      METHOD: The sample of the study was 735 elderly over 65 years old with basic
      livelihood security, who were conveniently selected from 245 public health
      centers nation-wide. Data collection was done using a structured questionnaire
      through interviews by visiting nurses. RESULT: The average number of present
      illnesses in the study subjects was 4.18. The average scores of ADL and IADL were
      15.903.39 and 9.772.97 respectively, which indicates a relatively independent
      everyday life. However, 64.2% of the subjects perceived their health status as
      'not healthy'. In terms of health promotion behaviors, 77.8% of the subjects had
      ceased smoking, 83.9% stopped drinking, 56.4% had a regular diet, 45.8% received
      regular physical check-ups during the past two years, and 66% received flu shots.
      Approximately 50% of the subjects were practicing 3-4 health promotion behaviors.
      Significant factors associated with health promotion behaviors were ADL, IADL and
      self-efficacy. CONCLUSION: Health promotion programs which focus on regular diet,
      exercise, and regular physical check-ups should be developed to improve
      independence of everyday life and quality of life among low-income elderly.

PMID- 15860941
TI  - [Development of an integrative cognitive rehabilitation program for brain injured
      patients in the post-acute stage].
AB  - PURPOSE: This study was conducted to develop a comprehensive cognitive
      rehabilitation program that can be easily applied to brain injured patients by
      family members or nurses in community or hospital settings. METHODS: A Systemic
      literature review design was used. Thirty-three related studies were reviewed.
      RESULT: Based on the results of the literature review, the training tasks for
      attention were designated to enhancing 4 hierarchical areas, i.e., focused,
      selective, alternating, and divided attention. On the other hand, the memory
      rehabilitation tasks mainly consisted of mnemonic skills, such as the association
      method which helps patients memorize given information by linking together common
      attributes, the visual imagery method, and self-instruction method. The problem
      solving rehabilitation program included a task of games or plays which stimulated
      the patients' curiosity and interest. The training tasks for problem solving were
      to encourage the process of deriving reasonable solutions for a problematic
      situation resembling real problems that the patients were faced with in their
      everyday life. CONCLUSION: It is expected that the cognitive rehabilitation
      program developed from this study could help patients having difficulty in their
      every day life, due to a reduced cognitive ability resulting from brain injury,
      to effectively adapt to every day life.

PMID- 15860933
TI  - Overexpression of protein kinase Cdelta enhances cisplatin-induced cytotoxicity
      correlated with p53 in gastric cancer cell line.
AB  - OBJECTIVE: An important issue in cancer therapy is to investigate the mechanism
      for cellular sensitivity to anticancer agents such as cisplatin. Cisplatin is one
      of the DNA-damaging agents and several factors including p53 are related to the
      sensitivity to cisplatin in cancer. Protein kinase C (PKC) delta is known as a
      positive regulator for cisplatin-induced cell death. In our present study, we
      examined whether overexpression of PKCdelta and p53 increases the sensitivity of
      the human gastric cancer cell line, MKN28, which has a mutation of p53 gene, to
      cisplatin. METHODS: Cell viability and DNA content were measured in MKN28 with
      adenovirus-mediated expression of PKCdelta and p53 after exposure to cisplatin.
      In addition, the active form of caspase-3 was detected by Western blotting.
      RESULTS: Overexpression of exogenous PKCdelta did not induce cell death in MKN28
      but inhibited cell growth at 1 microg/ml cisplatin as compared to that by
      cisplatin alone. Moreover, overexpression of both wild-type p53 and exogenous
      PKCdelta in MKN28 increased cisplatin-induced cell death in MKN28. CONCLUSION:
      These results suggest that PKCdelta, in cooperation with p53, possibly regulates
      cisplatin-induced caspase-3-mediated cell death in gastric cancer.

PMID- 15860940
TI  - [Health education program development for infants, toddlers and preschool
      children].
AB  - PURPOSE: The purpose of this study was to develop a health education program for
      child care workers of infants, toddlers and preschoolers to improve their care
      ability. The program provided child care teachers and children with information
      on how to take care of their health. METHOD: This program development was based
      on a systematic design of instruction by Dick & Carey(1996). The process included
      a review of literature, setting an instructional goal, getting advice from
      various experts, designing instruction and instructional medias, designing
      formative evaluation, revising the program and making a summative evaluations.
      RESULT: The products of this program were the 'Teachers Guide Book & CD-ROM.' The
      guide book included health education programs for infants, toddlers and
      preschoolers. The infant program included a basic baby care program for teachers.
      The toddlers and preschoolers program included basic health promotion, dental
      health, nutrition management, communicable disease prevention, substance abuse
      prevention and a safety program. CONCLUSION: These programs provided a systematic
      content of health education for children and their teachers, and useful data
      which can be applied to child care centers.

PMID- 15860942
TI  - [Self care activity, metabolic control, and cardiovascular risk factors in
      accordance with the levels of depression of clients with type 2 diabetes
      mellitus].
AB  - PURPOSE: The purpose of this study was to explore the levels of depression
      experienced by clients (N=152) with Type 2 Diabetes Mellitus(DM), and to compare
      the levels of self care activity, metabolic control and cardiovascular risk
      factors between depressed and non-depressed clients. METHOD: Participants aged 50
      and above were conveniently recruited in B city. The levels of depression, self
      care activity, metabolic control of glucose and lipids, and cardiovascular risk
      factors of the participants were measured by using questionnaires and blood tests
      from November, 2003 to June, 2004. Data was analyzed with descriptive statistics,
      Pearson correlation, Spearman rho and t-test using the SPSS WIN 10.0 program.
      RESULT: The prevalence of depression(CES-D=16) among the participants was 44.1%.
      The levels of self-care activities(p=.012), glucose(p=.019), total
      cholesterol(p=.022), LDL(.007) and cardiovascular risk factors(p=.012) were
      significantly higher in the depressed group than those in the non-depressed
      group. CONCLUSION: Based on the findings, we concluded that many DM patients
      experience depression and the depression of type 2 DM clients is significantly
      related with self care activities, diabetic control, and cardiovascular
      complications. However, this study did not address causality among these
      variables. Therefore, further research, such as a longitudinal cohort study, is
      needed to identify causality among these variables.

PMID- 15860943
TI  - [Concept analysis of endotracheal suctioning (ETS)].
AB  - PURPOSE: Concept analysis was performed on the behavioral concept of endotracheal
      suctioning (ETS), to identify the goal, to develop a standardized clinical
      protocol, to identify the antecedents and consequences, and to differentiate the
      improper use of ETS. METHOD: Walker & Avant's concept analysis was employed using
      clinical guidelines, books and review articles in which the procedures of ETS
      were written in detail and published in Pubmed within the last 20 years. RESULT:
      The macro-goal of ETS was to remove accumulated respiratory secretions. Three
      defining attributes of ETS were identified; catheter, suctioning and asepsis.
      Each attribute involved empirical referents, such as the size and depth of the
      catheter, the suction pressure, duration and method for suctioning. The
      antecedents of ETS were identical to the clinical evidences for the need of ETS
      such as the nursing assessment data. The consequences of ETS serve as an
      evaluation criteria on the effects of ETS based on the goal of ETS. CONCLUSION:
      The concept analysis of ETS demonstrates an example of considering a specific
      nursing protocol of ETS as a behavioral concept, applying concept analysis to it
      to identify it's key behavioral components as defining attributes and empirical
      referents and then developing and applying the standard ETS protocol.

PMID- 15860945
TI  - [An ethnographic study on eating styles of adult diabetics in Korea].
AB  - PURPOSE: The purpose of this study was to explore adult diabetics' eating styles
      and factors which influence them. METHOD: The study adopted an ethnographic
      method based on a perspective which views the eating style as a cultural
      phenomenon. Data was collected through a personal interview, participant
      observation, and documented materials from Oct. 2001 to Sept. 2002. In this
      study, fifteen adult diabetics, with an average age of 57, participated. Data
      analysis was done by the Spradley's taxonomic analysis technique. RESULT: The
      patients' eating styles were rooted in their viewpoint on illness as well as the
      meaning of food. Eating styles were classified into 4 types: Pathology-centered,
      symptom-centered, need-centered, and role-centered. CONCLUSION: A conventional
      approach to the treatment and management of diabetes did not consider the
      patient's inner world which may play an important role in the successful
      management of the disease. We found that it was critical for health care
      personnel to understand patients' values, beliefs and their way of life in order
      to facilitate the most successful self-care diet.

PMID- 15860944
TI  - [The effect of lavender aromatherapy on cognitive function, emotion, and
      aggressive behavior of elderly with dementia].
AB  - PURPOSE: This study was to develop an aromatherapy hand massage program, and to
      evaluate the effects of lavender aromatherapy on cognitive function, emotion, and
      aggressive behavior of elderly with dementia of the Alzheimer's type. METHOD: The
      Research design was a nonequivalent control group non-synchronized
      quasiexperimental study. Lavender aromatherapy was administrated to experimental
      group I for 2 weeks, jojoba oil massage was administrated to experimental group
      II for 2 weeks, and no treatment was administrated to the control group for 2
      weeks. Data was analyzed using the chi(2)-test, ANOVA, repeated measures of
      ANCOVA and ANCOVA in the SPSS program package. RESULT: 1. Experimental group I
      did not show significant differences in cognitive function in relation to the
      experimental group II and control group. 2. Experimental group I showed
      significant differences in emotion and aggressive behavior in relation to the
      experimental group II and control group. CONCLUSION: A Lavender aromatherapy hand
      massage program is effective on emotions and aggressive behavior of elderly with
      dementia of the Alzheimer's type.

PMID- 15860946
TI  - [The development of an organizational socialization process model for new nurses
      using a system dynamics approach].
AB  - PURPOSE: The purpose of this study was to examine the problems and relevant
      variables for effective Organizational Socialization of new nurses, to produce a
      causal map, to build up a simulation model and to test its validity. METHOD: The
      basic data was collected from Sep. 2002 to July 2003. The Organizational
      Socialization process of new nurses was analyzed through a model simulation. The
      VENSIM 5.0b DSS program was used to develop the study model. RESULT: This Model
      shows interrelation of these result variables: organizational commitment, job
      satisfaction, job performance, intention of leaving the work setting, decision
      making ability, and general results of Organizational Socialization. The model's
      factors are characteristic of organization and individual values, task-related
      knowledge and skills, and emotion and communication that affects new nurses'
      socialization process. These elements go through processes of anticipatory
      socialization, encounter, change and acquisition. The Model was devised to induce
      effective Organizational Socialization results within 24 months of its
      implementation. The basic model is the most efficient and will also contribute to
      the development of knowledge in the body of nursing. CONCLUSION: This study will
      provide proper direction for new Nurse's Organizational Socialization. Therefore,
      developing an Organizational Socialization Process Model is meaningful in a sense
      that it could provide a framework that could create effective Organizational
      Socialization for new nurses.

PMID- 15860947
TI  - [Dependency, abuse, and depression by gender in widowed elderly].
AB  - PURPOSE: The purpose of this study was to investigate the effects of dependency
      and abuse on depression according to gender in widowed elderly. METHOD: A
      convenient sample consisted of 246 widowed elderly who were more than 65 years
      old in four cities. Data was collected using a structured questionnaire from
      August to September, 2002. A dependency Scale developed by Ahn (1999) was used to
      measure the level of dependency. Emotional abuse and physical abuse were measured
      by 10 items for emotional abuse and 7 items for physical abuse selected out of
      the Conditions Scale of Elder Abuse. The level of depression was measured by the
      Geriatric Depression Scale (GDS). The SPSS WIN 11.0 version program was used for
      data analysis. RESULT: In male widowed elderly, dependency affected depression
      indirectly through emotional abuse. While in female widowed elderly, dependency
      affected depression directly and affected emotional abuse indirectly. CONCLUSION:
      The study showed that dependency was the most explainable variable on depression
      in widowed female elderly. Therefore, it dependency should be assessed first in
      nursing intervention to relieve depression of widowed elderly.

PMID- 15860948
TI  - [A study on health-related quality of life, smoking knowledge, smoking attitude,
      and smoking cessation intention in male smokers].
AB  - PURPOSE: This study was conducted to examine the relationship among health
      related quality of life, smoking knowledge, smoking attitude, and smoking
      cessation intention in male smokers. METHOD: The subjects were 259 male smokers
      in J city. The data was collected using structured questionnaires from Nov. to
      Dec. of 2003. The data was analyzed by the SPSS (ver.10.0) computer program, and
      it included descriptive statistics, t-test, ANOVA, the Pearson correlation
      coefficient, and Stepwise Multiple Regression. RESULT: The smoking cessation
      intention had a significant positive correlation among health-related quality of
      life (r=.159), smoking knowledge (r=.161), and smoking attitude (r=.127). These
      variables account for 26.8% of smoking cessation intention. CONCLUSION: These
      results suggested that the smoking cessation program to enhance the health
      related quality of life, smoking knowledge, and smoking cessation intention and
      to increase a negative influence on smoking attitude need to be developed.
      Therefore, these findings give useful information for constructing a smoking
      cessation program in male smokers.

PMID- 15860949
TI  - [A professional nursing practice environment and its impact on nurses' task
      motivation].
AB  - PURPOSE: This study was aimed at (a) describing professional nursing practice
      environments embedded in nursing care units and (b) examining its relationships
      to nurses' task motivation. METHOD: Using the Nursing Work Index Revised (NWI-R)
      and the Work Preference Inventory (WPI), a descriptive study was conducted with a
      sample of 320 registered nurses on 26 nursing care units in one University
      hospital in Korea. RESULT: Mean scores were 12.9 on a 5-20 score range of an
      autonomous environment scale, 7.3 on a 3-12 score range of a collaborative
      environment, and 15.8 on a 7-28 score range of control over nursing practice.
      Nurses' age, educational level, job position, working period at the hospital and
      employment status were significantly related to the degree of a professional
      practice environment. The extent to which a professional practice environment
      accounted for task motivation was 19.5%. CONCLUSION: There is a certain degree of
      professionalism in the workplace environment that nurses perceived within the
      nursing care units. When nurses care for patients, the degree of task motivation
      depends on the work environment supporting the professional nursing practice.

PMID- 15860951
TI  - [Effects of a taping method on pain and ROM of the knee joint in the elderly].
AB  - PURPOSE: This study was to investigate the effects of a taping method on pain and
      ROM of the knee joint in the elderly. METHOD: The subjects were seniors
      registered in a senior welfare center in D city. An experimental group of 30
      persons and a control group of 33 persons were chosen and according to the proper
      conditions and a knee pain score was marked from 1-5 on a Numerical Pain Rating
      Scale. For the experimental group, the taping method was conducted three times a
      week for four weeks (twelve times in all) but the control group did not receive
      taping. The measuring instrument of knee pain was a numerical pain rating scale
      from 0 to 10 and the ROM score was the average value of three measured values
      with a goniometer. The data was analyzed with SPSS WIN 10.0 using an chi(2)-test,
      t-test, repeated measures ANOVA, and time contrast. RESULT: Knee joint pain was
      significantly decreased in the experimental group over that of the control group
      (p=.001). In addition, knee joint ROM of the experimental group was significantly
      improved over that of the control group (p=.001). CONCLUSION: It was proven that
      the taping method was effective for pain relief and increasing ROM of the knee
      joint in the elderly.

PMID- 15860950
TI  - [Development of a scale to measure the effectiveness of oriental nursing
      education].
AB  - PURPOSE: The aim of this study was to design and evaluate a scale for measuring
      reliability and validity in the field of oriental nursing education. METHOD: A
      questionnaire was administered to 495 university nursing students using a
      convenience sampling method. The period of time for collecting data was from
      September 2003 to January 2004. RESULT: The derived outcome tool consisted of 6
      factors and 22 inquires on the basis of a conceptual frame of three domains
      (knowledge, attitude, and skill), As a result of the item analysis, 22 items were
      selected and the internal consistency alpha coefficient was .767. The value of
      Cronbach' Alpha of knowledge (factor 1) was .885, attitude (factor 2) was .756,
      and skill (factor 3) was .610. The three factors accounted for 65.110% of the
      variance in the total scale. Addressing the explanatory variance of each domain
      Cognitive domain was 22.477%, affective domain was 20.543%, and psychomotor
      domain was 17.090%. CONCLUSION: Further studies need to be done to verify
      educational evaluation and apply our outcomes to oriental nursing education.

PMID- 15860952
TI  - [A longitudinal study of critical thinking dispositions & critical thinking
      skills in baccalaureate nursing students].
AB  - PURPOSE: This longitudinal study was done to investigate critical thinking
      dispositions and critical thinking skills of nursing students enrolled in a 4
      year baccalaureate program at a university in Korea. METHOD: The study used a
      longitudinal design. A convenience sample of 32 nursing students who were
      completing their 1st, 2nd, 3rd, and 4th year in a baccalaureate program at a
      selected university was included. The subjects completed the California Critical
      Thinking Dispositions Inventory (CCTDI), the California Critical Thinking Skill
      Test (CCTST), and a demographic questionnaire. Data was analyzed by descriptive
      statistics, repeated ANOVA, adjusted p-values, and Pearson's correlation
      coefficient with SAS 8.12. RESULTS: There was statistically significant
      improvement according to academic year in the CCTDI total mean score (F=7.54, p=
      .0001) and subscales of Open-mindedness, Self-confidence, and Maturity.
      Contrarily, no statistically significant difference was found in the CCTST total
      mean score and subscales' score except Analysis. CONCLUSION: There is no
      significant correlation between critical thinking dispositions and skills, so it
      will be necessary to repeat a study like this, and the translated instruments
      should be modified by considering Korean culture.

PMID- 15860954
TI  - [Influencing factors that affect the psychological well-being in family
      caregivers of stroke patients].
AB  - PURPOSE: The purpose of this study was to investigate the factors that affect the
      psychological well-being in family caregivers of stroke patients. METHOD: The
      General Health Perception, short form 36, Health Survey Questionaire was used to
      measure health perception. The Caregiving Mastery Scale was used to assess the
      mastery, while the Psychological General Well-Being Index was used to examine the
      level of well-being. RESULT: Subjective health, caregiving mastery, patient's ADL
      and caregiving duration influenced on caregiver's psychological well-being.
      Subjective health had effect on psychological well-being both directly and
      indirectly. Caregiving duration and patient's ADL had indirect effect on
      psychological well-being through caregiving mastery. CONCLUSION: It is need to
      develop a health program for the caregivers of stroke patient's and to provide
      nursing intervention to improve the caregiver's ability, thereby improving the
      well-being of the family caregivers.

PMID- 15860953
TI  - [Prevalence rate and factors of myopia in preschool children].
AB  - PURPOSE: This study was aimed at providing basic data for developing a nursing
      intervention program which enables systematic and correct visual acuity care by
      discovering out visual acuity conditions, prevalence rate of myopia, and the
      factors related to myopia with Preschool children. METHOD: The subjects of this
      study consisted of 519 children between 3 and 6 years of age from 12
      kindergartens in Seoul which were selected through multiple cluster sampling.
      Myopia was defined as the spherical equivalent (SE) of more than -0.5 diopters
      (D) in the right eye. The data was analyzed by t-test, chi(2)-test, ANOVA, and
      logistic regression by using the SAS program. RESULT: The prevalence rate of
      myopia was 8.7%. the odds ratio of child myopia when one parent had myopia was
      2.2 times higher than when neither parent had myopia. The odds ratio of child
      myopia when reading more than three books per week was 0.27 times higher than
      reading less than three books. CONCLUSION: Myopia should be continuously and
      intensively managed from the age of 3.

PMID- 15860955
TI  - [Narrative analysis on survivor's experience of Daegu subway fire disaster--the
      hypothetical suggestions for disaster nursing practice].
AB  - Some fifty survivors participated in the narrative therapy sessions from March
      2003 to December 2004, and thirty cases were analyzed using the transcripts. Each
      participant's surviving story was summarized, and then interpreted and
      reinterpreted by the survivors themselves in collaboration with the researcher.
      The two main principles in narrative analysis were hermeneutical distanciation
      and hermeneutical circulation. RESULT AND CONCLUSION: First, nursing involvement
      should play active roles from the early stages of disaster incidents.
      Specifically, emergency nursing and flexible coping plans are to be available
      according to the specific properties of each case. Secondly, it is necessary to
      try to understand the extreme emotional experiences of disaster survival. The
      horror and pain people feel at an incident cannot simply be generalized, and it
      requires that each case be approached individually to help stop social
      alienation. Thirdly, more constant and long-term studies are required to set up
      nursing strategies for disaster survivors. Forming a trusting relationship with
      survivors is basic, and formally registering as participants is necessary for
      continuous interventions. Fourthly, we should deeply appreciate the danger and
      complexity of modern society and understand the complex nature of disaster.
      Fifthly, interdisciplinary activities and studies are necessary in combination
      with various other fields to establish a framework of total nursing care for
      disaster incidents. Lastly, it is urgently necessary to educate families and
      friends of the survivors and the society as a whole about life after a disaster.

PMID- 15860956
TI  - [Effects of a workbook program on the perceived stress level, maternal role
      confidence and breast feeding practice of mothers of premature infants].
AB  - PURPOSE: The purpose of this study was to identify the effects of a workbook
      program on percieved stress levels, maternal role confidence and breastfeeding
      practices of mothers of premature infants. METHOD: This study employed a quasi
      experimental non-equivalent pre-and-post test to compare the two groups. Data was
      collected from 32 subjects from March 10. to September 5, 2003 at an NICU located
      in S. city. In the sample, fifteen mothers were in the experimental group and
      seventeen were in the control group. A workbook program was provided twice during
      a period from two-three days after the baby's admission to one week after the
      first intervention. The instruments used were the PSS and self confidence scale.
      Data was analyzed by means of frequency, SD, chi(2)-test, Fisher's exact test,
      Mann-Whitney test, and the Wilcoxon signed rank test. RESULT: There was a
      significant difference in perceived stress levels between the experimental and
      control group (U=2.366, p=.018). There was not a significant difference in
      maternal role confidence between the two groups (U=1.002, p=.316). There was a
      significant difference in breastfeeding practice between the two groups (chi(2)=
      4.910, p=.035). CONCLUSION: It is concluded that a program using a workbook has a
      positive effect on decreasing the perceived stress level and increasing
      breastfeeding practice.

PMID- 15860957
TI  - New insights into NHEJ repair processes in prokaryotes.
AB  - In eukaryotic cells, the repair of DNA double strand breaks (DSBs) by the non
      homologous end-joining (NHEJ) pathway is critical for genome stability. Until
      recently it was assumed that this DSB repair pathway was restricted to the
      eukarya. However, a functionally homologous prokaryotic NHEJ repair apparatus has
      now been identified and characterised. In contrast to the complex eukaryotic
      system, bacterial NHEJ appears to require only two proteins, Ku and a
      multifunctional DNA ligase, which form a two-component repair complex at the
      termini of DSBs. Together, these DNA repair factors possess all of the break
      recognition, end-processing and ligation activities required to facilitate the
      complex task of DSB repair, both in vitro and in vivo. Our recent findings lay
      the foundation for understanding the molecular mechanisms that co-ordinate the
      processing and joining of DSBs by NHEJ in bacteria and also provides a conceptual
      framework for delineating the end-processing reactions in eukaryotes.

PMID- 15860958
TI  - The media, litigation, and the COX2 debate.

PMID- 15860959
TI  - A comparison of morning blood pressure surge in African Americans and whites.
AB  - African Americans have twice the risk of suffering a stroke compared to whites,
      but the reasons for this disparity have yet to be elucidated. Recent data suggest
      that the morning blood pressure (BP) surge is an independent predictor of
      strokes. Whether African Americans and whites differ with respect to morning BP
      surge is unknown. African-American (n=183) and white (n=139) participants, age 18
      65, were studied with 24-hour ambulatory BP monitoring. Morning surge was defined
      as morning BP minus the trough BP during sleep. The morning surge was
      significantly lower in African Americans than in whites (23 mm Hg vs. 27 mm Hg;
      both SEM=1.0; p=0.009). This relationship was no longer evident after adjusting
      for gender, age, and body mass index (23 mm Hg vs. 26 mm Hg; SE=1.0 and 1.1;
      p=nonsignificant). Morning BP surge is unlikely to account for differences in
      stroke incidence between African Americans and whites.

PMID- 15860960
TI  - Treatment of benign prostatic hyperplasia in hypertensive men.
AB  - As the proportion of the US population over the age of 65 continues to rise, it
      is likely that the number of individuals with concomitant benign prostatic
      hyperplasia and hypertension will also increase. To reduce morbidity and
      mortality, it is important to treat patients with hypertension optimally.
      Evidence from outcome trials suggests that alpha1 blockers should not be used as
      first-line antihypertensive therapy. Although some clinicians previously
      recommended alpha1 blocker monotherapy for patients with both hypertension and
      benign prostatic hyperplasia, the most recent American Urologic Association and
      Joint National Committee on Prevention, Detection, Evaluation, and Treatment of
      High Blood Pressure guidelines recommend independent treatment with the most
      appropriate pharmacologic agents for each condition. When treating patients with
      benign prostatic hyperplasia, clinicians should be aware of the potential impacts
      that alpha1 blockers may have on blood pressure and potential adverse events in
      patients who are normotensive as well as in patients with treated hypertension.

PMID- 15860961
TI  - David Ayman, MD: an early investigator of clinical hypertension.
AB  - Dr. David Ayman (1901-1986) was an astute clinician and observer who challenged
      medical dogma by performing placebo-controlled studies and by meticulous
      measurement of blood pressure under standardized conditions. He demonstrated that
      almost all drugs reported to have an antihypertensive effect in the early 20th
      century had achieved nothing more than placebo response. He noted the marked
      variability of blood pressure and devised methods to reduce that variability.
      These observations led to his publications concerning what is now known as "white
      coat" or office hypertension. He determined blood pressure personally in 1524
      members of 277 families over three generations and made observations on the
      hereditary nature of hypertension that countered the single-gene thinking of the
      day. His work is proof that clinical inquisitiveness, hard work, and the courage
      to challenge conventional wisdom can result in significant contributions to
      medicine and science.

PMID- 15860962
TI  - Secondary hypertension--whom and how do you study? What type of therapy is
      appropriate?
AB  - Following a hypertension symposium in Los Angeles, CA on October 20, 2004, a
      roundtable was convened to discuss secondary or treatable forms of high blood
      pressure, when and whom should be studied, and treatment methods. Dr. Marvin
      Moser, Clinical Professor of Medicine at Yale University School of Medicine, New
      Haven, CT, moderated the panel discussion. Participants included Dr. Ron Victor,
      from the Southwestern Medical Center, Dallas, TX and Dr. Joel Handler of the
      Orange County Kaiser Permanente Hypertension Clinic, Anaheim, CA.

PMID- 15860963
TI  - Hypertensive heart disease.
AB  - Hypertensive heart disease encompasses anatomical changes and altered physiology
      of heart muscle, coronary arteries, and great vessels. Left ventricular
      hypertrophy is not only a target organ response to increased afterload, but is
      also the most potent cardiovascular risk factor. Regression of hypertrophy
      reduces morbidity and mortality. Heart failure may be present in the absence of a
      reduction of myocardial contractility. Ischemic heart disease occurs in the
      absence of epicardial coronary disease. Left atrial size and atrial fibrillation
      are associated. Potentially lethal ventricular arrhythmias and sudden cardiac
      death are more common in hypertensive patients. The relationship of aortic root
      size to blood pressure is weaker than expected; however, the relationship to
      aortic dissection is stronger. Careful attention and treatment of left
      ventricular hypertrophy, heart failure, ischemic heart disease, and atrial
      fibrillation will improve survival.

PMID- 15860964
TI  - Interview with Alberto Zanchetti, MD.
AB  - This month, The Journal of Clinical Hypertension features a hypertension icon
      from outside of the United States. Professor Alberto Zanchetti of Milan, Italy
      has been one of the most prominent researchers and teachers in the field of
      hypertension in Europe for the past 40 years. Those of us who have attended the
      European or International Society of Hypertension meetings have marveled at his
      energy, breadth of knowledge, and his ability to translate science into clinical
      practice. He has been in the forefront of new drug research for many years and
      has chaired or participated in almost all of the guideline committees in Europe
      that have set policy and established hypertension treatment recommendations. My
      own memories of Alberto conjure images of a man who truly had influence, not only
      in medicine, but in the outside world as well. Professor Zanchetti delayed a TWA
      flight from Milan to New York when I was late in arriving at the airport. He
      convinced La Scala to present an unscheduled opera for attendees at the European
      Society of Hypertension in Milan. That gives a picture of the man who gets things
      done. For these gracious acts, and for his enormous positive influence on
      generations of physicians not only in Europe, but also around the world, we
      salute him as one of the icons in hypertension.

PMID- 15860965
TI  - What's new with kids and high blood pressure?

PMID- 15860966
TI  - Gynecomastia and hypertension.
AB  - Palpable dense and mobile subareolar tissue in the male breast defines the
      presence of gynecomastia. For the hypertension specialist, breast enlargement in
      men provides a clue to a secondary cause of hypertension or an adverse
      antihypertensive drug reaction. Hyperthyroidism, chronic renal failure, adrenal
      hyperplasia or tumors, amphetamine, cyclosporine, and anabolic steroids are
      secondary causes of hypertension associated with gynecomastia. Reserpine,
      methyldopa, and spironolactone are older drugs associated with gynecomastia;
      however, calcium antagonists (more commonly), angiotensin-converting enzyme
      inhibitors, and alpha1 blockers may also be associated with this finding.
      Treatment is directed to removal of the underlying cause.

PMID- 15860967
TI  - Renal cell carcinoma and hypertension.

PMID- 15860969
TI  - Clinical and hemodynamic effects of nesiritide (B-type natriuretic peptide) in
      patients with decompensated heart failure receiving beta blockers.
AB  - The use of beta blockers in congestive heart failure presents a therapeutic
      challenge for patients with acute episodes of decompensation. Such patients may
      be less responsive to positive inotropic agents, whereas the beneficial effects
      of nesiritide, which are not dependent on the beta-adrenergic receptor signal
      transduction pathway, may be preserved. This analysis of the Vasodilation in the
      Management of Acute CHF trial evaluated the safety and efficacy of nesiritide in
      decompensated congestive heart failure patients receiving beta blockers. The
      Vasodilation in the Management of Acute CHF trial was a multicenter, randomized,
      controlled evaluation of nesiritide in 489 hospitalized patients with
      decompensated congestive heart failure. One hundred twenty-three patients were on
      chronic beta-blocker therapy at enrollment (31 randomized to placebo, 50 to
      nesiritide, and 42 to nitroglycerin). Primary end points included pulmonary
      capillary wedge pressure and dyspnea evaluation at 3 hours. Patients receiving
      nesiritide, but not IV nitroglycerin, had significantly reduced pulmonary
      capillary wedge pressure vs. placebo at 3 hours regardless of beta-blocker use.
      The use of beta blockers did not alter the beneficial effects of nesiritide on
      systemic blood pressure, heart rate, or dyspnea evaluation. In nesiritide-treated
      subjects, safety profiles were similar regardless of beta-blocker use. Thus, the
      clinical and hemodynamic benefits and safety of nesiritide are preserved in
      decompensated congestive heart failure patients receiving chronic beta blockade.

PMID- 15860970
TI  - Brain natriuretic peptide and diastolic dysfunction in the elderly: influence of
      gender.
AB  - Diastolic heart failure is common in the elderly, particularly women. Previous
      studies on the value of brain natriuretic peptide in diastolic dysfunction have
      been largely limited to male subjects. The authors found that female gender, in
      addition to diastolic function, is an independent predictor of brain natriuretic
      peptide levels in the elderly without systolic ventricular dysfunction. The
      authors' data indicate that an optimal threshold of brain natriuretic peptide for
      detecting diastolic dysfunction should be gender-specific.

PMID- 15860971
TI  - Emergency department observation of heart failure: preliminary analysis of safety
      and cost.
AB  - Emergency-department (ED)-based observation-unit treatment has been shown to
      reduce inpatient admissions, hospital bed-hours, and costs without adversely
      affecting outcomes for several conditions. A sequential group design study
      compared risk-matched, acute decompensated heart failure patients admitted
      directly to the inpatient setting with those admitted to an ED observation unit
      for up to 23 hours before ED disposition. Outcomes were 30-day readmissions or
      repeat ED visits for heart failure or 30-day mortality. Estimates of bed-hours
      and charges between the groups were compared. Sixty-four patients were enrolled
      with 36 inpatient admissions and 28 observation unit patients. No patients died
      within 30 days. Observation unit patients had no significant difference in
      outcomes, a decrease in time from ED triage to discharge, a saving in mean bed
      hours, and less total charges. This pilot trial provides preliminary data that
      suggest admitted, low-risk heart failure patients may be safely and cost
      effectively managed in an ED-based observation unit. These findings need to be
      further evaluated in a randomized clinical trial.

PMID- 15860972
TI  - Genetic determinants of vascular oxidant stress and endothelial dysfunction.
AB  - Reactive oxygen species are products of cellular metabolism and function as
      normal signaling molecules in the vasculature. Overproduction of reactive oxygen
      species that outstrips antioxidant defenses generates oxidant stress that can
      lead to nitric oxide depletion and endothelial cell injury, and contributes to
      the pathophysiology of cardiovascular disease and myocardial dysfunction.
      Antioxidant enzymes that are important in limiting vascular oxidant stress
      include superoxide dismutases, catalase, glutathione peroxidases, and glucose-6
      phosphate dehydrogenase. The relevance of deficiencies in glutathione peroxidase
      and glucose-6-phosphate dehydrogenase on endothelial and myocardial dysfunction
      will be reviewed.

PMID- 15860973
TI  - Implantable pacing devices and sleep apnea: implications for diagnosis and
      therapy.
AB  - Sleep apnea has been increasingly recognized for its prevalence and its impact on
      cardiovascular health. The disorder has considerable impact on cardiovascular
      disease states, particularly congestive heart failure. Implantable cardiac pacing
      devices may have a role in both the diagnosis and therapy of sleep apnea, which
      may be of particular importance given the seemingly wide coprevalence of cardiac
      disorders and sleep apnea.

PMID- 15860974
TI  - Mesenchymal stem cells: future source for reparative medicine.
AB  - Current treatments for ischemic cardiomyopathy are aimed toward minimizing the
      deleterious consequences of damaged myocardium. The possibility of treating heart
      failure by generating new myocardium and vascular structures has provided major
      impetus for recent stem cell research. Mesenchymal stem cells (MSCs), also
      referred to as marrow stromal cells, differentiate into a wide variety of
      lineages, including myocardial smooth muscle and possibly endothelial cells. The
      multilineage potential of MSCs, their ability to elude detection by the host's
      immune system, and their relative ease of expansion in culture make MSCs a very
      promising source of stem cells for transplantation. This paper reviews animal and
      human trials studying the role of MSCs in cardiomyogenesis and vasculogenesis in
      postinfarct myocardium, factors that stimulate MSC differentiation, routes of MSC
      delivery, and methods of detecting MSC engraftment.

PMID- 15860975
TI  - Mesenchymal stem cells: future source for reparative medicine.

PMID- 15860978
TI  - Historical vignettes in heart failure.

PMID- 15860979
TI  - Brain injury and ventricular dysfunction: insights into reversible heart failure.
AB  - The unique syndrome of brain death is associated with cardiac dysfunction;
      however, if such a heart is removed from this environment and transplanted, the
      cardiac dysfunction often resolves. This scenario offers insight into the
      mechanisms of reversible forms of cardiac injury and suggests that treatment of
      the extra-cardiac milieu by removing the initiating insult can often result in
      recovery. The mechanisms leading to reversible cardiac dysfunction are discussed
      in this review, with concentration on the implications of such injury in
      determining outcomes following transplantation.

PMID- 15860982
TI  - High-density lipoprotein subclass distribution in individuals of Asian Indian
      descent: the National Asian Indian Heart Disease Project.
AB  - Individuals of Asian Indian descent have significantly higher cardiovascular
      event rates as compared with other ethnic groups. The authors investigated the
      prevalence of metabolic disorders linked to coronary artery disease in an Asian
      Indian male population compared with non-Asian Indian males. Standard lipid
      measurements did not discriminate between groups, and the Asian Indian group
      exhibited less of the high coronary artery disease risk small low-density
      lipoprotein trait. Despite less of the small low-density lipoprotein trait in the
      Asian Indian group and no difference in high-density lipoprotein cholesterol, the
      Asian Indian group had a significantly higher prevalence (p < 0.0002) of low high
      density lipoprotein 2b, implying impaired reverse cholesterol transport. This
      observation remained significant in the subgroup of patients with high-density
      lipoprotein cholesterol over 40 mg/dL, a region felt not to reflect impaired
      reverse cholesterol transport. Low high-density lipoprotein 2b combined with the
      higher lipoprotein(a) in the Asian Indian group may help explain the high
      prevalence of coronary artery disease in this ethnic population.

PMID- 15860983
TI  - Effect of fixed-dose ACE-inhibitor/calcium channel blocker combination therapy
      vs. ACE-inhibitor monotherapy on arterial compliance in hypertensive patients
      with type 2 diabetes.
AB  - Assessment of vascular compliance may be a useful measurement of the clinical
      effects of antihypertensive treatment. Both angiotensin-converting enzyme (ACE)
      inhibitors and calcium channel blockers are known to improve vascular elasticity.
      A study was performed to test the hypothesis that combined therapy with an ACE
      inhibitor and a calcium channel blocker would have additive benefits on vascular
      compliance at similar levels of blood pressure (BP), as compared with monotherapy
      with an ACE inhibitor. This 12-week, double-blind study was a substudy of a
      larger clinical hypertension study conducted in patients with hypertension and
      type 2 diabetes. Subjects (N = 20) were randomized to either a fixed-dose
      combination of amlodipine besylate/benazepril HCl or to enalapril monotherapy.
      BP, heart rate, large- and small-vessel compliance, systemic vascular resistance,
      and urinary microalbumin excretion were assessed at baseline and after treatment.
      Both treatments were similarly effective in lowering BP, reducing systemic
      vascular resistance, and decreasing urinary microalbumin excretion. Improvement
      in large-vessel compliance was significantly greater among subjects who received
      ACE-inhibitor/calcium channel blocker combination therapy (52%) as compared with
      those who received ACE-inhibitor monotherapy (32%; p < 0.05). No significant
      change in small-vessel compliance was observed with either treatment. Greater
      improvement in large-vessel compliance with combination therapy was independent
      of BP lowering.

PMID- 15860984
TI  - Adverse events with concomitant amiodarone and statin therapy.
AB  - The authors reviewed adverse events (AEs) reported to the United States Food and
      Drug Administration to determine the percentage of statin-associated AE reports
      with concurrent amiodarone use for simvastatin, atorvastatin, and pravastatin.
      AEs affecting the following organ systems were analyzed: muscle, liver, pancreas,
      and bone marrow. The percentage of simvastatin reports with concurrent amiodarone
      use was 1.0%, compared with 0.7% of the atorvastatin-associated reports (p = not
      significant). The percentage of pravastatin reports with concurrent amiodarone
      use was 0.4% (p < 0.05 for pravastatin vs. simvastatin). Muscle toxicity was the
      most commonly reported statin-amiodarone AE, accounting for 77% of the reports.
      AEs tended to occur in older male patients (mean age, 76 years), who were on
      multiple other medications (mean number of other medications, five). Clinicians
      should be vigilant about muscle-related complaints in patients concomitantly
      taking amiodarone, especially in elderly patients on multiple medications. Use of
      a statin not metabolized through the cytochrome P450-3A4 system may be
      appropriate in this setting.

PMID- 15860985
TI  - The role of statins in preventing stroke.
AB  - Epidemiological studies have not demonstrated a clear relationship between stroke
      risk and hypercholesterolemia. Clinical trials using statins have demonstrated a
      reduction in stroke, in particular, in patients with established coronary artery
      disease. The disparity between epidemiological and clinical studies suggests
      hypercholesterolemia is a true risk factor for stroke that evaded detection in
      epidemiological studies, or that statins possess other properties that render
      them useful in stroke prevention. These effects have been loosely termed
      "pleiotropic" in the lipid literature and revolve around putative effects of
      statins on endothelial function, inflammation, thrombosis, plaque stability, and
      immune regulation. Questions remain as to the mechanisms of benefit of statin
      therapy in stroke prevention, the role of statins in the primary prevention of
      stroke, and the role of statins in modulating the immune system in the brain.

PMID- 15860987
TI  - The unsung perils of peripheral arterial disease: a malady in search of a
      patient.
AB  - Peripheral arterial disease (PAD) is increasingly recognized as a strong
      predictor of mortality and morbidity from atherosclerotic events, especially from
      coronary heart disease. Since vascular disease remains the most common cause of
      death in the world, the substantial prevalence, ease of diagnosis, and ominous
      prognosis have increased interest in PAD among the prevention community. The
      association with coronary heart disease is strong enough that for prevention
      purposes, PAD should be considered a high-risk condition that demands aggressive
      therapy to reduce incident vascular events. Unlike other forms of atherosclerotic
      disease, PAD is easily diagnosed in the outpatient clinic noninvasively, using
      the ankle brachial index. Because its diagnosis can thus be seamlessly integrated
      into the routine clinical encounter, the ankle brachial index has emerged as a
      tool for global risk assessment. This article will review the relationship
      between PAD and other vascular disease, emphasizing the role of PAD in prevention
      efforts.

PMID- 15860986
TI  - Walking and Non-HDL-C in adults: a meta-analysis of randomized controlled trials.
AB  - An elevated level of non-high-density lipoprotein cholesterol (non-HDL-C) is a
      major risk factor for cardiovascular disease. The purpose of this study was to
      use the meta-analytic approach to examine the effects of walking on non-HDL-C in
      adults. Twenty-two randomized controlled trials representing 30 outcomes from 948
      subjects (573 exercise, 375 control) met our inclusion criteria. Across all
      designs and categories, random effects modeling resulted in a significantly
      greater decrease in the walking group when compared with the control group of
      approximately 4% for non-HDL-C (+/- standard error of the mean, -5.6+/-1.8 mg/dL,
      95% confidence interval, -8.8 to -2.4 mg/dL). Meta-regression showed a
      statistically significant association between changes in non-HDL-C and the year
      of publication, with greater reductions associated with more recent publication
      year (R2 = 0.23, p = 0.005). The results of this meta-analytic review suggest
      that walking reduces non-HDL-C in adult humans.

PMID- 15860988
TI  - Use of the cell phone for transmission of the pulse rate from a subject in
      motion.
AB  - A method of transmitting the sound produced by cardiac electrical activity to a
      remote site using the cell phone is described. The use of the cell phone system
      permits transmission of the click produced by the heartbeat from a subject in
      motion who may be far away, as well as in close proximity.

PMID- 15860989
TI  - Point: uses of carotid plaque measurement as a predictor of cardiovascular
      events.
AB  - Vascular prevention is most cost-effective in high-risk patients, but secondary
      prevention misses many opportunities. The high-risk strategy- identifying
      patients with high levels of risk factors-is problematic because traditional risk
      factors predict only half of vascular events. In multiple regression, traditional
      risk factors explained only half of carotid atherosclerosis. New strategies are
      being explored, such as electron-beam computerized tomographic measurement of
      coronary calcification, to identify high-risk patients. Carotid plaque is a
      powerful tool for identifying and managing high-risk vascular patients, as it
      explains twice as much of unexplained vascular risk as coronary calcium by
      electron beam computerized tomography, and it has significant advantages compared
      with intimal-medial thickness. After adjustment for risk factors, patients in the
      highest quartile of baseline plaque area have 3.5 times the risk of stroke,
      death, or myocardial infarction compared with those in the lowest quartile. Those
      with regression or stable plaque have half the risk of those with progression
      after adjustment for the same panel of risk factors. The therapeutic target is
      plaque regression or stabilization, not just control of traditional risk factors.
      Trying to treat arteries without measuring plaque is like trying to treat
      hypertension without measuring the pressure, or hyperlipidemia without measuring
      the lipids.

PMID- 15860990
TI  - Counterpoint: carotid ultrasound-an essential investigation in the prevention of
      coronary artery disease?
AB  - The accompanying article asserts that measurement of carotid plaque area by
      ultrasonography adds a vital, new dimension to the investigation and management
      of patients at risk of developing coronary artery disease. The author contends
      also that traditional risk factors for coronary artery disease have failed to
      provide a basis for either predicting cardiovascular events or guiding effective
      therapy. Carefully acquired epidemiological data have established beyond
      reasonable doubt that traditional risk factors identify individuals who are
      likely to develop coronary artery disease. Further, effective management of these
      factors have been remarkably effective in preventing cardiovascular events. There
      is little prospective data in randomly selected populations to indicate that
      ultrasound examinations of the carotid arteries provides additional new
      information which would argue in favor of an alternative therapeutic approach for
      patients likely to develop coronary artery disease.

PMID- 15860991
TI  - PEACE and CAMELOT.

PMID- 15860992
TI  - Benefit on atherosclerosis of adding niacin in patients with low HDL-cholesterol
      taking a statin.

PMID- 15860993
TI  - Effectiveness of a computerized system for intravenous heparin administration:
      using information technology to improve patient care and patient safety.
AB  - To overcome errors in prescribing, calculating doses, and monitoring intravenous
      heparin, a computerized heparin nomogram system (HepCare) was developed to
      improve heparin safety using interactive cues between the prescriber, nurse,
      pharmacist, and the laboratory. The frequency of deviations decreased from 0.5
      per patient before HepCare with the protocol to 0.006 per patient with HepCare
      and the protocol. The goal activated partial thromboplastin time results of the
      HepCare system (group I) were compared with patients who were not treated using
      the HepCare system (group II). There was a higher mean percentage of activated
      partial thromboplastin times within goal range in group I vs. II-44% vs. 27%
      (p<0.01). There were reminders of a drop in platelet count in 6% of patients,
      hemoglobin drop in 0.7%, and validation activated partial thromboplastin time
      values in 7% of patients by HepCare. HepCare-guided intravenous heparin resulted
      in significant improvements in safety, quality assurance, and targeted activated
      partial thromboplastin time values.

PMID- 15860994
TI  - Low-molecular-weight heparin in patients with acute ST-segment elevation
      myocardial infarction.
AB  - One of the primary goals of physicians treating patients presenting to a hospital
      with acute ST-segment elevation myocardial infarction is to restore the flow of
      blood in the infarct-related artery as quickly as possible. Prompt and successful
      reperfusion limits the size of the myocardial infarction, reduces left
      ventricular dysfunction, and improves the patient's chance of survival.
      Approximately two thirds of patients with ST-segment elevation myocardial
      infarction do not present to a hospital capable of conducting urgent direct
      percutaneous coronary intervention or cardiac surgery when it is needed. They
      must receive pharmacological reperfusion therapy, a combination of fibrinolytic,
      antiplatelet, and anticoagulant drugs. Earlier and simpler administration of
      pharmacological reperfusion therapy could result in significantly improved
      outcomes. Fibrinolytic therapy, in combination with adjunctive antithrombin
      therapy that is simpler and quicker to administer (e.g., tenecteplase with
      enoxaparin), may be more efficacious and easier to use than regimens involving
      unfractionated heparin.

PMID- 15860995
TI  - Electronic health record systems: the vehicle for implementing performance
      measures.
AB  - Advances in information technology and recent national directives have the
      potential to support dramatic improvements in health care. Two key components are
      the implementation of functional electronic health record systems and widely
      accepted, evidence-based clinical performance measures for physicians. Midwest
      Heart Specialists, a 55-physician cardiovascular group at 14 locations in
      northern Illinois, has utilized an outpatient electronic health record system
      since 1997. Since 2003, the group has integrated cardiovascular measurement sets
      developed by the American Medical Association-convened Physician Consortium for
      Performance Improvement into its electronic health record system. With this
      integration, the group was able to capture data needed for internal quality
      assessment and improvement as part of routine outpatient care without the need
      for additional resources. Critical disease-management data for decision support
      are available continuously, resulting in improvements in health care. The
      reporting of these standardized data could be the foundation to support quality
      based reimbursement strategies and physician office-based disease-management
      strategies.

PMID- 15860996
TI  - Atrial septal abnormalities and cryptogenic stroke: a paradoxical science.
AB  - Patent foramen ovale and/or atrial septal aneurysm occur in up to 20% of the
      general population, and have been linked to cryptogenic ischemic strokes in
      younger individuals. The pathophysiologic basis of this association remains
      unclear, with growing evidence suggesting a role for thrombosis and embolization.
      Aspirin and warfarin constitute the current mainstay of medical therapy, with a
      variety of secondary prevention studies assessing their impact on stroke
      recurrence. To date, the quality of published data preclude the development of
      strict recommendations, but a number of suggestions can be derived from available
      literature. Patients with isolated patent foramen ovale or atrial septal aneurysm
      and a first ischemic stroke respond well to either aspirin or warfarin therapy.
      On the other hand, oral anticoagulation seems to be the preferred medical therapy
      in higher-risk patients with both patent foramen ovale and atrial septal aneurysm
      or those with multiple strokes on aspirin. Percutaneous or surgical patent
      foramen ovale closures have been proposed as alternative therapies and seem
      effective in reducing stroke recurrence. In the absence of randomized, controlled
      trials comparing medical and invasive approaches, the adoption of a particular
      therapy should take into consideration the individual's preference, clinical
      presentation, risk profile, lifestyle, and the expertise of the local
      interventional and surgical teams.

PMID- 15860997
TI  - Metabolic syndrome, subclinical coronary atherosclerosis, and cardiovascular
      risk.
AB  - The metabolic syndrome is a constellation of cardiovascular disease risk factors,
      and it is associated with the presence of advanced subclinical coronary
      atherosclerosis. The presence of the metabolic syndrome appears to provide
      incremental predictive value on top of the Framingham risk score in predicting
      future cardiovascular events. Traditional risk-prediction formulas fail to
      account for a significant portion of coronary heart disease morbidity and
      mortality. The metabolic syndrome may be particularly useful in predicting risk
      among individuals classified as low or intermediate risk by Framingham risk
      score.

PMID- 15860998
TI  - The role of hospitalists in the management of acute decompensated heart failure.
AB  - Heart failure and episodes of acute decompensated heart failure have an important
      effect on the US health care system, especially the elderly Medicare population.
      Efforts to improve the quality of care for patients hospitalized with acute
      decompensated heart failure have focused on creating standardized treatment
      guidelines based on substantial clinical evidence, but inadequate implementation
      of these guidelines continues to result in excess morbidity and mortality from
      heart failure. Hospitalists specializing in inpatient treatment strategies may
      play an important role in implementing clinical guidelines because their main
      commitment is to overall clinical treatment of inpatients. This review focuses on
      current recommended guidelines for diagnosis, treatment, and long-term management
      of patients with acute decompensated heart failure and the hospitalist's role in
      providing the oversight needed to adhere to these guidelines and manage this
      complex disease state.

PMID- 15860999
TI  - The US Army Center for Cardiovascular Diseases, 1918 US Army General Hospital No.
      9, Lakewood, NJ.

PMID- 15861000
TI  - The Ohio State University Richard M. Ross Heart Hospital: design and function of
      a specialty hospital in the academic environment.

PMID- 15861001
TI  - Partners for success: Avera Heart Hospital of South Dakota.
AB  - Avera Heart Hospital of South Dakota has been very successful. This success can
      be attributed to the equal three-way partnership and the strengths that each of
      the partners has brought to the venture.

PMID- 15861002
TI  - Carcinoid heart disease: echocardiographic recognition and differential
      diagnosis.

PMID- 15861003
TI  - Double dissociated tachycardias: isorhythmic A-V dissociation at rapid atrial and
      ventricular rates.

PMID- 15861004
TI  - Genetic testing for risk stratification in hypertrophic cardiomyopathy and long
      QT syndrome: fact or fiction?
AB  - PURPOSE OF REVIEW: Hypertrophic cardiomyopathy, affecting 1 in 500 persons, is
      the most common identifiable cause of sudden cardiac death in the young, whereas
      congenital long QT syndrome, affecting 1 in 5000 persons, is perhaps one of the
      most common causes of autopsy negative sudden unexplained death. Since May 2004,
      genetic testing has been available as a clinical diagnostic test for both
      hypertrophic cardiomyopathy and long QT syndrome. It is now critical to carefully
      scrutinize the relationships between genotype and phenotype as they pertain to
      clinical practice. RECENT FINDINGS: In 1990, the molecular underpinnings of
      hypertrophic cardiomyopathy were exposed with the identification of a mutation in
      the MYH7-encoded beta myosin heavy chain. Since then, hundreds of mutations
      scattered among at least 14 genes confer the pathogenetic substrate for this
      'disease of the sarcomere'. In 1995, the discipline of cardiac channelopathies
      was born with the revelation that mutations in critical cardiac channel genes
      cause long QT syndrome. Today, hundreds of mutations involving several cardiac
      channel genes account for approximately 75% of long QT syndrome. Over the past
      decade, scores of genotype-phenotype correlation studies in both hypertrophic
      cardiomyopathy and long QT syndrome have been conducted. SUMMARY: Genomic
      medicine has now entered the clinical practice as it pertains to the evaluation
      and management of both hypertrophic cardiomyopathy and long QT syndrome. The
      diagnostic utility of genetic testing for both diseases is clearly evident, as
      well as current limitations. While treatment decisions are certainly influenced
      by knowing the underlying genotype in long QT syndrome, there seems to be
      negligible prognostic value associated with particular hypertrophic
      cardiomyopathy-causing mutations at this time.

PMID- 15861005
TI  - Molecular genetics of coronary artery disease.
AB  - PURPOSE OF REVIEW: Coronary artery disease, including its most severe
      complication myocardial infarction, is the leading cause of death; however, its
      genetic studies lag behind other diseases. Many advances have recently been made,
      however, and these are reviewed here. RECENT FINDINGS: Positional cloning based
      on genome-wide linkage analysis with large families identified the first non -
      lipid-related disease-causing gene, MEF2A (encoding a transcriptional factor),
      for coronary artery disease and myocardiaI infarction. The MEF2A mutations may
      account for up to 1.93% of the disease population; thus, genetic testing based on
      mutational analysis of MEF2A may soon be available for many coronary artery
      disease/myocardial infarction patients. Genome-wide association studies
      identified significant association for myocardiaI infarction with the LTA gene
      (encoding lymphotoxin-alpha), and a follow-up study found that an LTA-interacting
      gene, LGALS2 (encoding galectin-2), is also a susceptibility gene for myocardiaI
      infarction. Studies that employ genome-wide linkage scans with hundreds of small
      nuclear families have identified new susceptibility genes for coronary artery
      disease and myocardiaI infarction, including ALOX5AP (encoding 5-lipoxygenase
      activating protein) associated with myocardial infarction and stroke and PDE4D
      (encoding phosphodiesterase 4D) for ischemic stroke. SUMMARY: Genetic studies
      provide new insights into the pathogenesis of coronary artery disease and
      myocardial infarction. Future studies will focus on identification of new disease
      causing genes and susceptibility genes, exploration of the molecular mechanisms
      by which mutations cause coronary artery disease/myocardiaI infarction, and gene
      specific therapies for patients.

PMID- 15861006
TI  - Ankyrin-based cardiac arrhythmias: a new class of channelopathies due to loss of
      cellular targeting.
AB  - PURPOSE OF REVIEW: This review addresses a new mechanism for arrhythmia due to
      abnormal cellular localization of membrane ion channels and transporters. The
      focus is on ankyrins, a family of proteins that localize diverse membrane ion
      channels and transporters, and recent evidence that mutations affecting functions
      of ankyrins result in cardiac arrhythmia. RECENT FINDINGS: A loss-of-function
      mutation of ankyrin-B in humans and a null mutation in mice result in a
      dominantly-inherited fatal cardiac arrhythmia initially classified as type 4 long
      QT syndrome. Characterization of additional probands suggests ankyrin-B mutations
      cause a new cardiac arrhythmia syndrome associated with sinus node dysfunction
      that is distinct from long QT syndrome. Ankyrin-B mutation results in elevated
      calcium transients in cardiomyocytes accompanied by loss of cellular targeting of
      Na/K ATPase, Na/Ca exchanger, and InsP3 receptor (all ankyrin-binding proteins)
      to cardiomyocyte membrane domains. The principal voltage-gated Na channel in
      heart, Nav1.5, is directly associated with ankyrin-G, which is encoded by a
      distinct gene from ankyrin-B. Mutation of Nav1.5 causing loss of binding to
      ankyrin-G results in Brugada syndrome and loss of targeting of Nav1.5 to the cell
      surface of cardiomyocytes. SUMMARY: Ankyrin-B and ankyrin-G are recently
      recognized constituents of the heart that target diverse ion
      channels/pumps/transporters to physiologic sites of action in cardiomyocytes.
      Mutations of ankyrin-B cause a newly defined cardiac arrhythmia syndrome
      associated with abnormal calcium homeostasis in a mouse model. Ankyrin-G
      associates with the principal voltage-gated Na channel in the heart, and loss of
      this interaction due to mutation of Nav1.5 results in Brugada syndrome.

PMID- 15861007
TI  - Molecular genetics of Marfan syndrome.
AB  - PURPOSE OF REVIEW: Marfan syndrome, the founding member of connective tissue
      disorders, is characterized by involvement of three major systems (skeletal,
      ocular, and cardiovascular) due to alteration in microfibrils. FBN1 at 15q21.1
      was found to cause Marfan syndrome in 1991, and in 2004 TGFBR2 at 3p24.1 was
      newly identified as the Marfan syndrome type II gene. Several studies implied
      that fibrillin-1 and transforming growth factor-beta (TGF-beta) signaling are
      functionally related in extracellular matrix. Identification of TGFBR2 mutations
      in Marfan syndrome type II provided the direct evidence of the relation in
      humans. RECENT FINDINGS: More than 500 FBN1 mutations have been found in Marfan
      syndrome, tentative genotype - phenotype correlations have emerged, and mouse
      models are providing insight into pathogenic mechanisms. TGFBR2 mutations are
      still limited, however, in 2005 were also reported to cause a new aneurysm
      syndrome. Functional association between fibrillin-1 and TGF-beta signaling in
      extracellular matrix has been presented. SUMMARY: This review focuses on recent
      molecular genetics advances in Marfan syndrome and overlapping connective tissue
      disorders. Mutation spectrum of FBN1 and TGFBR2 in relation to phenotype is
      presented. Functional relation between fibrillin-1 and TGF-beta signaling is
      discussed. Future prospects in the study of Marfan syndrome are presented.

PMID- 15861008
TI  - Novel markers for heart failure diagnosis and prognosis.
AB  - PURPOSE OF REVIEW: This paper reviews recent advances in heart failure biomarkers
      for identification of disease precursors, subclinical disease, and onset or
      progression of overt disease. RECENT FINDINGS: Heart failure biomarkers can be
      categorized empirically as neurohormonal mediators, markers of myocyte injury and
      remodeling, and indicators of systemic inflammation. Brain natriuretic peptide is
      the most widely studied, with a potentially important but evolving role for
      determining prognosis and as a surrogate endpoint in clinical trials. Strong
      evidence exists for use of brain natriuretic peptide in the diagnosis of acute
      heart failure and for improved clinical outcomes with a brain natriuretic peptide
      guided approach to heart failure care. The use of brain natriuretic peptide as a
      screening tool for asymptomatic left ventricular systolic dysfunction, or to
      distinguish systolic from diastolic heart failure, is not supported by current
      data. Markers of myocyte injury, including troponins, heart-type fatty acid
      binding protein, and myosin light chain-1, may further improve heart failure
      prognostication in conjunction with plasma brain natriuretic peptide. Biomarkers
      of matrix remodeling and inflammation have emerged as potential preclinical
      indicators to identify individuals at risk of developing clinical heart failure.
      A role for cellular adhesion molecules may also emerge in identifying those at
      risk for cardiovascular thrombotic complications, such as stroke. SUMMARY: The
      spectrum of heart failure biomarkers and their potential clinical applications
      continues to grow. Ongoing research on multimarker strategies will likely
      identify biomarker combinations that are optimal at various stages during the
      evolution of heart failure, ranging from their use for screening, diagnosis,
      determining prognosis, and guiding management.

PMID- 15861009
TI  - Matrix modulation and heart failure: new concepts question old beliefs.
AB  - PURPOSE OF REVIEW: Myocardial remodeling is a complex process involving several
      molecular and cellular factors. Extracellular matrix has been implicated in the
      remodeling process. Historically, the myocardial extracellular matrix was thought
      to serve solely as a means to align cells and provide structure to the tissue.
      Although this is one of its important functions, evidence suggests that the
      extracellular matrix plays a complex and divergent role in influencing cell
      behavior. This paper characterizes some of the notable studies on this dynamic
      entity and on adverse myocardial remodeling that have been published over the
      past year, which further question the belief that the extracellular matrix is a
      static structure. RECENT FINDINGS: Progress has been made in understanding how
      the extracellular matrix is operative in the three major conditions (myocardial
      infarction, left ventricular hypertrophy due to overload, and dilated
      cardiomyopathy) that involve myocardial remodeling. Several studies have examined
      plasma profiles of matrix metalloproteinases and tissue inhibitors of matrix
      metalloproteinases following myocardial infarction and during left ventricular
      hypertrophy as surrogate markers of remodeling/remodeled myocardium. It has been
      demonstrated that bioactive signaling molecules and growth factors, proteases,
      and structural proteins influence cell-matrix interactions in the context of left
      ventricular hypertrophy. Finally, studies that either removed or added tissue
      inhibitor of metalloproteinases species in the myocardium demonstrated the
      importance of this regulatory protein in the remodeling process. SUMMARY:
      Understanding the cellular and molecular triggers that in turn give rise to
      changes in the extracellular matrix could provide opportunities to modify the
      remodeling process.

PMID- 15861012
TI  - Neonatal hemochromatosis: is it an alloimmune disease?

PMID- 15861011
TI  - Overweight children and adolescents: a clinical report of the North American
      Society for Pediatric Gastroenterology, Hepatology and Nutrition.
AB  - Childhood overweight and obesity are major health problems with immediate and
      long-term consequences of staggering magnitude. Despite this, there are few
      preventive and therapeutic strategies of proven effectiveness available to public
      health and clinical practitioners. Accruing such evidence is currently and
      appropriately a health policy priority, but there is an urgent need to intervene
      even before comprehensive solutions are fully established. The aim of this
      Clinical Report on Overweight Children and Adolescents is to present information
      on current understanding of pathogenesis and treatment of overweight and obesity.
      We report on the epidemiology, molecular biology and medical conditions
      associated with overweight; on dietary, exercise, behavioral, pharmacological and
      surgical treatments; and on the primary prevention of overweight in children and
      adolescents.

PMID- 15861013
TI  - The National Children's Study takes off.

PMID- 15861014
TI  - Evaluation of stool antigen test for Helicobacter pylori infection in
      asymptomatic children from a developing country using 13C-urea breath test as a
      standard.
AB  - OBJECTIVE: Prevalence of asymptomatic Helicobacter pylori infection is very high
      in infants and children in developing countries. C urea breath test (UBT) is a
      reliable non-invasive diagnostic test for H. pylori infection in children that
      avoids invasive endoscopy. We compared a newly introduced H. pylori stool antigen
      test (with a high sensitivity and specificity in symptomatic children) with UBT
      in asymptomatic children mostly 1-5 years old, from a population with a high
      prevalence of infection. METHOD: Eighty six asymptomatic children (42 boys and 44
      girls) were tested for H. pylori infection using the UBT and a stool antigen test
      (HpSA) based on a sandwich enzyme immunoassay for antigen detection. RESULTS:
      Forty five of the eighty-six (52.3%) children tested positive for H. pylori using
      the breath test. In 34 of these forty-five children, H. pylori antigen was
      detected in stool (sensitivity = 75.6%, 95% CI = 63 to 88%). Of the 50 of 86
      (58%) children positive by HpSA test, 34 were positive for breath test. Of the 41
      children with negative UBT test 25 were negative for stool antigen test
      (specificity = 61%, 95% CI = 46 to 76%). CONCLUSION: The sensitivity and
      specificity of the new stool antigen test are lower in asymptomatic children with
      high H. pylori prevalence rate compared to those reported for children with
      gastrointestinal symptoms. Its usefulness is limited for diagnosis in an
      asymptomatic child with H. pylori infection.

PMID- 15861015
TI  - Validation of food frequency questionnaire for assessing dietary macronutrients
      and calcium intake in Italian children and adolescents.
AB  - OBJECTIVES: To validate a food frequency questionnaire to determine calcium and
      macronutrient intake in healthy children and adolescents. MATERIALS AND METHODS:
      The questionnaire consisted of 16 main food groups containing the main foods
      composing the diet of Italian children, a total of 136 items and 23 questions
      about food habits, supplements and servings. Color photographs to identify
      serving size were included. The questionnaire was validated by comparing it with
      the 7-day weighed record method in 37 healthy volunteers in two different age
      groups: children aged 6 - 10 years (n = 18) and adolescents aged 16 - 20 years (n
      = 19). RESULTS: The food frequency questionnaire seemed to overestimate the
      nutrient intake when compared with 7-day weighed records; however the two methods
      were highly correlated for all the nutrients considered. The range of Pearson's
      correlations between energy and nutrient intake (protein, fat, carbohydrates and
      calcium) determined from food frequency questionnaire and 7-day weighed record
      were 0.5-0.6 in children and 0.5-0.8 in young adults. Agreement between the two
      methods in classifying relative intakes was examined by determining the frequency
      of similar classification into terciles. Two thirds of the subjects were
      correctly classified for most nutrients, with a very low (2% to 5%) percentage of
      grossly misclassifications. DISCUSSION: The food frequency questionnaire has
      proved adequate to rank a pediatric population in terms of calcium and
      macronutrient intakes. The ranking of subjects is extremely useful for
      epidemiologic studies evaluating the relation between nutrient intake and
      disease.

PMID- 15861016
TI  - Malabsorption of carbohydrates and depression in children and adolescents.
AB  - BACKGROUND: Previous studies have shown an association between sugar
      malabsorption and depressive symptoms in adult women. Incompletely absorbed
      sugars may form nonabsorbable complexes with tryptophan, an amino acid precursor
      of serotonin, decreasing its availability. As serotonin is the most important
      neurotransmitter involved in depressive disorders, its depletion could lead to
      the onset of depression. METHODS: The authors' aim was to study the possible
      association between malabsorption of sugars (lactose and fructose) and depressive
      symptoms in adolescent patients of Spanish origin. The authors studied two groups
      of patients. Group G included 14 patients previously diagnosed with sugar
      intolerance. In these, the authors assessed depressive symptoms. Group P
      consisted of seven patients suffering from major depression. In these, the
      authors performed functional sugar absorption tests. The authors studied the
      metabolic pathway of tryptophan in both groups. RESULTS: In the group with sugar
      malabsorption, there was a 28.5% prevalence of depressive symptoms that was
      higher than expected in our population. In the group with depression, the authors
      found a higher than expected prevalence of sugar intolerance (71.42% versus 15%
      in controls). CONCLUSIONS: The unexpected prevalences obtained for the groups
      studied suggest that there may be an association between sugar intolerance and
      depressive symptoms during adolescence.

PMID- 15861017
TI  - Nutritional status in adolescents and young adults with screen-detected celiac
      disease.
AB  - OBJECTIVE: To describe the nutritional status in patients with screen-detected
      celiac disease (CD). METHODS: Nutritional status was assessed by serum tests and
      anthropometric measures in 26 subjects (16 to 25 years of age) with biopsy-proven
      CD and 29 healthy control subjects (16 to 21 years of age) with negative tissue
      transglutaminase antibodies (16 to 22 years of age); all the subjects were
      selected from the cohort of 3654 schoolchildren. RESULTS: Compared with control
      subjects, CD patients had lower median values of whole blood folic acid (91
      versus 109 nmol/L; P = 0.01), serum ferritin (14 versus 27 microg/L; P = 0.028)
      and pre-albumin (0.21 versus 0.28 g/L; P </= 0.001) and higher transferrin
      receptor (1.3 versus 1.1; P = 0.008) and serum transferrin receptor-ferritin
      index (1.2 versus 0.7; P = 0.006). Folic acid concentration was subnormal in 31%
      of the CD subjects (versus 14% of the controls) and iron status (transferrin
      receptor-ferritin index) was subnormal in 30% (versus 14%). Body mass index was
      not different in females of the CD and control groups (22 versus 22 kg/m2) or in
      the males of the respective groups (25 versus 24 kg/m2). Females with CD were
      shorter than the controls (mean 162 versus 167 cm; P = 0.018), but no difference
      was found in males. No association was found between the nutritional status and
      the markers of mucosal injury (villous-crypt measures), but titer of
      transglutaminase was associated with whole blood folic acid (r = -0.5; P = 0.016)
      and with transferrin receptor-ferritin index (r = 0.4, P = 0.05). CONCLUSIONS:
      One third of screen-detected adolescent CD subjects have abnormalities in folate
      or iron status that call for early diagnosis and dietary treatment of the disease
      to prevent nutritional deficiencies.

PMID- 15861018
TI  - Treatment regimens for Helicobacter pylori infection in children: is in vitro
      susceptibility testing helpful?
AB  - BACKGROUND: Treatment regimens for Helicobacter pylori have variable success
      rates, and data comparing effectiveness with respect to strain sensitivity are
      relatively scarce. OBJECTIVE: To evaluate the efficacy of two treatment regimens
      for eradication of H. pylori and the impact of bacterial susceptibility testing.
      STUDY DESIGN: 265 children endoscopically diagnosed with H. pylori infection were
      randomly assigned to receive omeprazole + amoxicillin with clarithromycin or
      omeprazole + amoxicillin with metronidazole. Bacterial culture and susceptibility
      was performed in a subgroup. Eradication was assessed by C-urea breath test.
      RESULTS: Eradication was achieved in 73.4% by omeprazole + amoxicillin with
      metronidazole and in 62.6% by omeprazole + amoxicillin with clarithromycin (P =
      0.078). H. pylori was cultured successfully in 105 patients. Resistance to
      metronidazole was detected in 31.4% of the isolates and resistance to
      clarithromycin in 15%. Eradication rate by omeprazole + amoxicillin with
      metronidazole for metronidazole-susceptible bacteria (N = 38) was 90%, and for
      resistant bacteria (N = 19) it was 42%. Only 75% of clarithromycin-sensitive
      strains were successfully treated by omeprazole + amoxicillin with
      clarithromycin, and none of the cases with clarithromycin-resistant strains
      responded to omeprazole + amoxicillin with clarithromycin treatment. CONCLUSION:
      There is a trend of greater efficacy of eradication with omeprazole + amoxicillin
      with metronidazole versus omeprazole + amoxicillin with clarithromycin therapy.
      Although resistance negatively influences eradication, first-line sensitivity
      based treatment would be expected to improve this rate only slightly.
      Susceptibility testing should probably be reserved only for treatment failures.

PMID- 15861019
TI  - Etiology, outcome and prognostic indicators of childhood fulminant hepatic
      failure in the United kingdom.
AB  - OBJECTIVE: To study the etiology, outcome and prognostic indicators in children
      with fulminant hepatic failure in the United Kingdom. DESIGN: Retrospective
      review of all patients <17 years with fulminant hepatic failure from 1991 to
      2000. Fulminant hepatic failure was defined as presence of coagulopathy
      (prothrombin time >24 seconds or International Normalized Ratio >2.0) with or
      without hepatic encephalopathy within 8 weeks of the onset of symptoms. SETTING:
      Liver Unit, Birmingham Children's Hospital, United Kingdom. RESULTS: Ninety-seven
      children (48 male, 49 female; median age, 27 months; range, 1 day-192.0 months)
      were identified with fulminant hepatic failure. The etiologies were: 22
      metabolic, 53 infectious, 19 drug-induced, and 3 autoimmune hepatitis. The
      overall survival rate was 61%. 33% (32/97) recovered spontaneously with
      supportive management. Fifty-five children were assessed for liver
      transplantation. Four were unstable and were not listed for liver
      transplantation; 11 died while awaiting liver transplantation. Liver
      transplantation was contraindicated in 10 children. Of the 40 children who
      underwent liver transplantation, 27 survived. Children with autoimmune hepatitis,
      paracetamol overdose or hepatitis A were more likely to survive without liver
      transplantation. Children who had a delay between the first symptom of liver
      disease and the onset of hepatic encephalopathy (median, 10.5 days versus 3.5
      days), higher plasma bilirubin (299 micromol/L versus 80 micromol/L), higher
      prothrombin time (62 seconds versus 40 seconds) or lower alanine aminotransferase
      (1288 IU/L versus 2929 IU/L) levels on admission were more likely to die of
      fulminant hepatic failure or require liver transplantation (P < 0.05). On
      multivariate analysis, the significant independent predictors for the eventual
      failure of conservative therapy were time to onset of hepatic encephalopathy >7
      days, prothrombin time >55 seconds and alanine aminotransferase </=2384 IU/L on
      admission. CONCLUSIONS: Children with fulminant hepatic failure with severe
      coagulopathy, lower alanine aminotransferase on admission and prolonged duration
      of illness before the onset of hepatic encephalopathy are more likely to require
      liver transplantation. Early referral to a specialized center for consideration
      of liver transplantation is vital.

PMID- 15861020
TI  - Long-term outcome of intractable ulcerating enterocolitis of infancy.
AB  - BACKGROUND: Chronic enterocolitis is rare in infancy and accounts for less than
      0.5% of all newly diagnosed inflammatory bowel disease (IBD) in the UK.
      Presentation at this young age is usually indicative of underlying
      immunodeficiency/immunodysregulation. A group of such infants suffer intractable
      ulcerating enterocolitis of infancy (IE) in which there is a pan-enteritis with
      marked oro-anal involvement and deep flask like mucosal ulcers throughout the
      colon. METHODS: Retrospective review of presenting features, treatment and long
      term outcome in a series of 8 children with typical IE. RESULTS: The 8 children
      were aged between 1 and 4 weeks at onset (median 2 weeks, mean 2.3 weeks), of
      which 7 were followed up for 2-22 years (median 7.5 years, mean 11 years). All 8
      children had an intractable disease course requiring a colectomy for control of
      symptoms. The median age at colectomy was 1.7 years (range 4 months-4 years).
      Three children developed a generalised lymphadenopathy due to uncontrolled EBV
      related lymphoid proliferations (ages 4, 12, 18). These comprised a monomorphous
      B-lymphoycte lympho-proliferative disorder, a large pleomorphic follicular
      lymphoma, and a high grade pleomorphic B cell non-Hodgkin's lymphoma.
      CONCLUSIONS: Infants with IE have a high risk of developing lymphomatous
      proliferations that appears to be related to the underlying immunodysregulation.
      Use of aggressive immunosuppression and acquisition of EBV infection appears to
      accelerate this process; hence we advocate early colectomy in confirmed cases. In
      children with IE screening for EBV and vigilance for abnormal lymphoid
      proliferations is paramount.

PMID- 15861021
TI  - Changes in intestinal morphology and permeability in the biobreeding rat before
      the onset of type 1 diabetes.
AB  - OBJECTIVE: Type 1 diabetes is an autoimmune disorder that occurs in genetically
      susceptible individuals. It has been hypothesized that the disease could be
      triggered by environmental agents that gain entry into the body through small
      intestinal absorption. Increased intestinal permeability has been reported both
      in spontaneous animal models of type 1 diabetes and human type 1 diabetes. In
      these studies, we examined both the physical and functional permeability
      characteristics of the small intestine in diabetes-prone and control rats.
      METHODS: In a series of studies, BioBreeding diabetes-prone(n = 31), BioBreeding
      diabetes-resistant (n = 20) and control Wistar (n = 25) rats were examined at
      intervals from 21 to 125 days of age. RESULTS: The percentage of goblet cells and
      the mucosal crypt depth were significantly greater in BioBreeding diabetes-prone
      than BioBreeding diabetes-resistant rats (P < 0.001 and P = 0.01, respectively).
      BioBreeding diabetes-prone and BioBreeding diabetes-resistant rats expressed less
      of the tight junction protein claudin (P < 0.05) and exhibited greater intestinal
      permeability (P < 0.001) than did Wistar rats. Intestinal permeability measured
      both in vivo and ex vivo decreased in all rat strains as age increased (P <
      0.001). CONCLUSIONS: In a genetically susceptible rodent model of diabetes, early
      increased intestinal permeability might allow unregulated passage of
      environmental antigens that could potentially trigger the autoimmune response
      leading to type 1 diabetes.

PMID- 15861022
TI  - Effective opiate-receptor antagonist therapy of cholestatic pruritus induced by
      an oral contraceptive.

PMID- 15861023
TI  - Variceal hemorrhage 13 years after nephrectomy for Wilms tumor.

PMID- 15861024
TI  - Cecal diverticulitis in an adolescent.

PMID- 15861025
TI  - Heterotopic gastric mucosa in the gallbladder: a rare cause of massive hemobilia.

PMID- 15861026
TI  - Clinical quiz. Uremia.

PMID- 15861027
TI  - Autoimmune thyroid disease in children with celiac disease.

PMID- 15861029
TI  - Pharmacogenetics in the treatment of depression: pharmacodynamic studies.
AB  - The pharmacological treatment of mood disorders has reduced their morbidity and
      improved mental health for millions of individuals worldwide, favouring a
      considerable reduction of the direct and indirect costs caused by these common
      pathologies. Unfortunately, not all individuals benefit, and 30-40% of patients
      do not show a complete response to treatment. Efficient clinical predictors are
      not available, although genetic factors are thought to play a substantial (but
      complex) role in the antidepressant response. Pharmacogenetics, which
      investigates the influence of genetic features on the pharmacological response,
      has gained increasing attention and holds great promise for clinical psychiatry.
      Here, a brief overview is provided on the various pharmacogenetic studies
      published to date that analyse the commonest treatments for depression:
      antidepressants, sleep deprivation and lithium salts.

PMID- 15861030
TI  - Patients with an ApoE epsilon4 allele require lower doses of coumarin
      anticoagulants.
AB  - OBJECTIVE: Vitamin K is an essential cofactor for the synthesis of several blood
      coagulation factors. It has been suggested that the apolipoprotein E (ApoE)
      genotype has profound effects on vitamin K status. Therefore, we investigated
      whether this common genetic polymorphism influenced dose requirements and effects
      of coumarin anticoagulants. METHODS: We did a cohort study in 1637 patients from
      an outpatient anticoagulation clinic treated with acenocoumarol or phenprocoumon.
      RESULTS: To attain the same level of anticoagulation, patients with genotype
      epsilon4/epsilon4 and genotype epsilon3/epsilon4 required respectively 3.4 mg
      (95%CI: -6.0 to -0.9) and 0.8 mg (95%CI: -1.6 to 0.1) acenocoumarol per week less
      than patients with genotype epsilon3/epsilon3. Patients homozygous for the
      epsilon2 allele required 3.5 mg (95%CI: 0.1 to 6.9) acenocoumarol per week more
      than patients with genotype epsilon3/epsilon3. The acenocoumarol maintenance dose
      showed a gene dose effect of the epsilon4 allele, but not of the epsilon2 allele.
      No significant dose difference was observed for phenprocoumon, possibly because
      of low numbers. CONCLUSION: The ApoE genotype affects the dose requirements of
      acenocoumarol.

PMID- 15861031
TI  - Mortality in patients with hypertension on angiotensin-I converting enzyme (ACE)
      inhibitor treatment is influenced by the ACE insertion/deletion polymorphism.
AB  - BACKGROUND: The response to angiotensin-I converting enzyme (ACE)-inhibitor
      therapy is highly variable. Residual ACE activity during treatment, potentially
      modified by the ACE insertion/deletion (I/D) polymorphism, may explain part of
      this variability. We studied the possible interaction between ACE-inhibitor
      therapy in patients with hypertension and the ACE I/D polymorphism in incident
      heart failure and death. METHODS: We studied 3365 hypertensive participants of
      the population-based Rotterdam Study, without heart failure at baseline for whom
      ACE-genotyping was successful. Incident heart failure was defined according to
      established criteria. In addition, total and cardiovascular mortality were
      studied as endpoints. A Cox regression model with use of ACE-inhibitors defined
      as time-dependent covariates was used for data-analysis. Interaction was tested
      in this model assuming an allele-effect relationship. RESULTS: Although we could
      not demonstrate a beneficial effect of ACE-inhibitors, there was significant
      interaction between the ACE I/D polymorphism (II-ID-DD) and ACE-inhibitor use in
      the prediction of total and cardiovascular mortality. Mortality risk associated
      with treatment increased with the number of D alleles present; e.g. for total
      mortality in the II genotype group: RR=0.95 (95% CI 0.63-1.45), in the ID
      genotype group: RR=1.08 (95% CI 0.84-1.38) and in the DD genotype group: RR=1.61
      (95% CI 1.18-2.18). No statistically significant interaction was found for
      incident heart failure. CONCLUSION: The results of our study suggest a relative
      resistance to ACE-inhibitor therapy in subjects with hypertension and the DD
      genotype compared to the II genotype, with the ID genotype in an intermediate
      position.

PMID- 15861032
TI  - Genetic analysis and functional characterization of polymorphisms in the human
      concentrative nucleoside transporter, CNT2.
AB  - The concentrative nucleoside transporter CNT2 (SPNT1; SLC28A2) plays a role in
      the absorption and disposition of naturally occurring nucleosides, as well as
      nucleoside analog drugs. The aim of the present study was to characterize genetic
      variation in SLC28A2, the gene encoding CNT2, and to functionally analyse non
      synonymous variants of CNT2, as a first step towards understanding whether
      genetic variation in this nucleoside transporter contributes to variation in
      response to nucleoside analogs. As part of a larger study, DNA samples from an
      ethnically diverse population (100 African-Americans, 100 European-Americans, 30
      Asians, 10 Mexicans and seven Pacific Islanders) were screened and 10 coding
      region variants of CNT2 were identified. The non-synonymous variants were then
      constructed and characterized in Xenopus laevis oocytes. Six non-synonymous
      variants were identified, and all were able to transport guanosine. The four
      common variants (>1% in the sample population) were further characterized with
      the anti-viral nucleoside analog drug ribavirin. No differences were observed
      among the four common variants in the uptake kinetics of 3H-ribavirin (Km in
      microM: 35.6+/-9.27 for CNT2-reference, 40.7+/-6.47 for CNT2-P22L, 31.2+/-15.8
      for CNT2-S75R, 26.7+/-6.13 for CNT2-S245T and 49.9+/-14.6 for CNT2-F355S). The
      variant CNT2-F355S exhibited a change in specificity for the naturally occurring
      nucleosides, inosine and uridine. All non-synonymous variants of CNT2 took up
      guanosine, and the four variants examined showed no significant difference in
      ribavirin kinetics. However, CNT2-F355S (3% allele frequency in the African
      American sample) was found to alter specificity for naturally occurring
      nucleosides, which may have implications for nucleoside homeostasis.

PMID- 15861033
TI  - Strong linkage disequilibrium at the nucleotide analogue transporter ABCC5 gene
      locus.
AB  - The ABCC5 transporter is a ubiquitously expressed ATP-dependent efflux pump that
      exports nucleotide analogues, including thiopurine anticancer drugs and antiviral
      drugs. Polymorphisms within this gene may be associated with differences in
      response to these drugs between different individuals. Haplotype mapping may
      facilitate the identification of causal genetic variations in association
      studies. Here, we report the characterization of the haplotype and linkage
      disequilibrium (LD) profiles across the entire 100 kb of the ABCC5 gene in five
      ethnically unique populations. Of 24 single nucleotide polymorphisms (SNPs)
      examined, 16 were observed to occur at high frequency in all five populations and
      were used for further haplotype and LD analyses. The ABCC5 gene was found to be
      in strong LD in all populations with half-length LD (LD0.5) estimated to be
      between 106 and 293 kb long and useful LD extending beyond 100 kb. Low haplotype
      diversity was observed in the four non-African populations, where the total
      number of observed haplotypes constituted less than 22% of the predicted number
      of haplotypes in a simulated population that has undergone maximum recombination.
      Four and six tagging SNPs, which could account for approximately 90% of observed
      haplotypes, were identified in the non-African and African-American populations,
      respectively.

PMID- 15861034
TI  - Identification and functional characterization of novel CYP2J2 variants: G312R
      variant causes loss of enzyme catalytic activity.
AB  - CYP2J2 plays important roles in the metabolism of therapeutic drugs, such as
      astemizole and ebastine, as well as endogenous fatty acids. This study aimed to
      identify CYP2J2 genetic variants in Koreans and to characterize their functional
      consequences. From direct sequencing of the CYP2J2 gene, 12 genetic variations,
      including the two novel nonsynonymous mutations G312R and P351L, were identified
      from 93 Korean subjects. The two novel CYP2J2 variants were co-expressed with
      NADPH-cytochrome P450 reductase in Sf9 cells and their catalytic activities were
      quantified. The recombinant CYP2J2 G312R variant showed almost complete loss of
      enzymatic activity, as determined by CYP2J2-catalysed astemizole O-demethylation
      and ebastine hydroxylation. The CYP2J2 P351L variant showed enzymatic activities
      that were comparable with the wild-type CYP2J2. The reduced CO spectra of the
      recombinant CYP2J2 proteins suggested no CO binding to the heme in CYP2J2 G312R.
      In addition, molecular modelling of the three-dimensional structure consistently
      predicted that there might be spatial hindrance between heme and the bulky side
      chain of the R312 residue in CYP2J2 G312R variant. The CYP2J2 G312R variant was
      not found in 192 Chinese, 99 African-Americans, 100 Caucasians and 159 Vietnamese
      subjects. Two of the 192 Chinese subjects (0.52%) were heterozygous for CYP2J2
      P351L. Twelve CYP2J2 variants, including two novel nonsynonymous variants, were
      identified in a Korean population. The G312R variant is the first nonfunctional
      CYP2J2 allele to be identified, and is expected to influence the disposition of
      its substrate therapeutics, as well as endogenous compounds.

PMID- 15861035
TI  - Nicotine metabolism: the impact of CYP2A6 on estimates of additive genetic
      influence.
AB  - To conduct a pharmacogenetic investigation of nicotine metabolism in twins. One
      hundred and thirty nine twin pairs [110 monozygotic (MZ) and 29 dizygotic (DZ)]
      underwent a 30-min infusion of stable isotope-labelled nicotine and its major
      metabolite, cotinine, followed by an 8-h in-hospital stay. Blood and urine
      samples were taken at regular intervals for analysis of nicotine, cotinine and
      metabolites by gas chromatography-mass spectrometry or liquid chromatography-mass
      spectrometry and subsequent characterization of pharmacokinetic and metabolism
      phenotypes. DNA was genotyped to confirm zygosity and for variation in the gene
      for the primary enzyme involved in nicotine metabolism, CYP2A6 (alleles tested:
      *1, *1x2, *2, *4, *7, *9 and *12). Univariate biometric analyses quantified
      genetic and environmental influences on each pharmacokinetic measure in the
      presence and absence of covariates, including measured CYP2A6 genotype. The best
      fitting model identified a substantial amount of variation in the weight-adjusted
      rate of total clearance of nicotine attributable to additive genetic influences
      [59.4%, 95% confidence interval (CI)=44.7-70.7]. The majority of variation in the
      clearance of nicotine via the cotinine pathway was similarly genetically
      influenced (60.8%, 95% CI=46.9-71.5). Heritability estimates were reduced to
      54.2% and 51.8%, respectively, but remained substantial after taking into account
      the effect of variation in CYP2A6 genotype. These results suggest the involvement
      of additional genetic factors (e.g. uncharacterized or novel CYP2A6 alleles as
      well as other genes in the metabolic pathway) that remain to be identified.

PMID- 15861036
TI  - Vitamin D receptor genotypes influence the success of calcitriol therapy for
      recurrent vertebral fracture in osteoporosis.
AB  - Osteoporosis is a complex multi-factorial disease where environment, diet and
      genetics play a role in determining susceptibility. Patients with existing
      vertebral fracture have a heightened risk of further recurrent vertebral
      fracture. The efficacy of new osteoporosis therapies is often compared to calcium
      supplementation. 1,25-dihydroxyvitamin D3 (calcitriol) acts through the vitamin D
      receptor (VDR) and is effective at reducing recurrent vertebral fracture risk.
      Because the VDR controls calcium metabolism, we hypothesized that genetic
      variation at the VDR locus may influence response to both calcium and calcitriol
      therapy. Postmenopausal women with osteoporosis from a 3-year study comparing
      calcitriol versus calcium for prevention of vertebral fractures were genotyped
      for VDR alleles detected by FokI, BsmI, ApaI and TaqI. Data were analysed by
      hierarchical log-linear analysis and robust analysis of variance for
      relationships to fracture outcomes. Significant differences in the vertebral
      fracture rate in response to calcium therapy were observed between VDR genotypes
      (P<0.001). Calcium appeared to be equally effective as calcitriol in particular
      genotypes. The response to calcitriol therapy was most pronounced in patients
      carrying the TaqI t allele in combination with the FokI f initiation codon
      variant: f+t+ carriers were 11.3-fold less likely to sustain recurrent vertebral
      fracture in the last 2 years of the trial while on calcitriol therapy compared to
      calcium (P=1.4x10(-5)). Response to both calcium and calcitriol therapy is
      dependent on genetic variation at the VDR locus and two loci in the VDR gene may
      contribute to this effect.

PMID- 15861037
TI  - Association between beta-1 and beta-2 adrenergic receptor gene polymorphisms and
      the response to beta-blockade in patients with stable congestive heart failure.
AB  - Previous studies have clearly demonstrated the beneficial effect of beta-blockers
      in patients with stable congestive heart failure (CHF). beta-blockers improve
      left ventricular ejection fraction (LVEF) and reduce cardiac mortality. However,
      there is an interindividual variability in the response to these agents. Two
      studies have suggested a possible impact of some functional betaAR gene
      polymorphisms on the effects of beta-blockade. The objective of the study is to
      analyse the association between genetic variations in the beta1 or the beta2
      adrenoreceptor (AR) gene and the effects of beta-blockade in patients with stable
      CHF. We studied 199 consecutive patients with stable CHF not treated with beta
      blockers. Before introduction of beta-blockers and 3 months after the maximal
      tolerated dose was reached, patients underwent an echocardiography and a
      radionuclide angiography. The beta1ARGly389Arg, beta1ARSer49Gly, beta2ARGly16Arg,
      beta2ARGln27Glu and beta2ARThr164Ile polymorphisms were determined: beta-blockade
      resulted in a significant decrease in heart rate, a significant increase in LVEF
      (from 30+/-10% to 40+/-13%, P<0.0001). There was no association between the five
      polymorphisms and heart rate or LVEF, either before or after beta-blockade. Heart
      rate and LVEF responses to beta-blockade were not associated with the beta1AR or
      the beta2AR polymorphisms. betaAR polymorphisms did not explain the
      interindividual variability in the response to beta-blockers.

PMID- 15861038
TI  - Sympathoneural and adrenomedullary functional effects of alpha2C-adrenoreceptor
      gene polymorphism in healthy humans.
AB  - OBJECTIVES: alpha2-Adrenoreceptors restrain sympathetic nervous outflows and
      inhibit release of noradrenaline from sympathetic nerves. In-frame deletion of
      the alpha2C-adrenoreceptor subtype (alpha2CDel322-325) increases the risk of
      congestive heart failure. Increased delivery of catecholamines to cardiovascular
      receptors might explain this increased risk. METHODS: Twenty-nine healthy African
      Americans genotyped for alpha2-adrenoreceptor subtype polymorphisms underwent 3H
      noradrenaline and 3H-adrenaline intravenous infusion and arterial blood sampling
      for measurements of rates of entry of endogenous noradrenaline and adrenaline
      into arterial plasma (total body spillovers) by the tracer dilution technique.
      Eleven subjects were homozygotes for the alpha2CDel322-325 polymorphism, nine
      heterozygotes, and nine non-carriers. Subjects were studied during supine rest
      and during and after i.v. infusion of the alpha2-adrenoreceptor antagonist,
      yohimbine. RESULTS: At rest, homozygotes for the alpha2CDel322-325 polymorphism
      had higher total body noradrenaline spillover than did heterozygotes (t=2.90,
      df=18, P=0.023) or non-carriers (t=3.22, df=18, P=0.010). Adrenaline spillover
      was higher in homozygotes than non-carriers (t=2.61, df=18, P=0.045).
      Administration of yohimbine produced larger, more sustained increments in
      noradrenaline spillover, heart rate, and anxiety in homozygotes than in the other
      groups. CONCLUSION: In healthy people, alpha2CDel322-325 polymorphism is
      associated with increased sympathetic nervous and adrenomedullary hormonal
      activities, both during supine rest and during pharmacologically evoked
      catecholamine release. Polymorphisms of the alpha2C-adrenoreceptor may help
      explain individual differences in predisposition to a variety of disorders of
      catecholaminergic function, such as cardiovascular disorders, depression or
      anxiety disorders.

PMID- 15861039
TI  - CYP2D6 polymorphisms and the risk of tardive dyskinesia in schizophrenia: a meta
      analysis.
AB  - The present study aimed to evaluate whether there is any association between
      CYP2D6 alleles and susceptibility to tardive dyskinesia in patients with
      schizophrenia under treatment. A meta-analysis considered case-control studies
      determining the distribution of genotypes for any CYP2D6 polymorphism in
      unrelated tardive dyskinesia cases and controls without tardive dyskinesia among
      patients with schizophrenia who were treated with antipsychotic agents. Loss of
      function alleles were grouped together in a single comparison, whereas other
      alleles (2 and 10) were examined separately. Data were available for eight (n=569
      patients), three (n=325 patients) and four (n=556) studies evaluating the effect
      of the loss of function alleles, the 2 allele and the 10 allele, respectively.
      Summary odds ratios (ORs) suggested that loss of function alleles increased the
      risk of tardive dyskinesia significantly [OR=1.43, 95% confidence interval (CI)
      1.06-1.93, P=0.021], whereas there was no effect for 2 and inconclusive evidence
      for 10 (OR=0.82, 95% CI 0.50-1.32, P=0.41 and OR=1.19, 95% CI, 0.89-1.60, P=0.24,
      respectively). Patients who were homozygotes for loss of function alleles (poor
      metabolizers) had 1.64-fold greater odds of suffering tardive dyskinesia compared
      to other patients with schizophrenia, but the effect was not formally significant
      (95% CI 0.79-3.43). For the risk conferred by loss of function alleles, large
      studies provided more conservative estimates of a genetic effect than smaller
      studies (P=0.003). CYP2D6 loss of function alleles may predispose to tardive
      dyskinesia in patients with schizophrenia under treatment, but bias cannot be
      excluded.

PMID- 15861040
TI  - Polymorphisms of vitamin D receptor gene protect against the risk of head and
      neck cancer.
AB  - Vitamin D has potent anti-tumour properties. Calcitriol [1,25(OH)2D3], the
      hormonal derivative of vitamin D3, is an antiproliferative and prodifferentiation
      factor for several cell types, including human squamous cells of the head and
      neck. Several polymorphisms of the vitamin D receptor (VDR) gene have been
      described, including a FokI restriction fragment-length polymorphism (RFLP) in
      exon 2 and an adjacent TaqI RFLP in exon 9. We hypothesized that the VDR FokI and
      TaqI polymorphisms are associated with the risk of developing squamous cell
      carcinoma of the head and neck (SCCHN). We conducted a hospital-based, case
      control study of 719 SCCHN cases and 821 cancer-free controls (all non-Hispanic
      Whites) to assess the association between VDR polymorphisms and SCCHN risk. The
      cases and controls were frequency-matched on age, sex and ethnicity.
      Polymorphisms at the TaqI and FokI restriction sites were determined from genomic
      DNA by polymerase chain reaction-RFLP methods. Both homozygous variant genotypes
      (ff and tt) were associated with a decreased risk of SCCHN [odds ratio (OR)=0.72,
      95% confidence interval (CI)=0.53-0.98 and OR=0.64, 95% CI=0.47-0.87,
      respectively] compared to the common FF and TT genotypes. The VDR variant
      genotypes were associated with a decreasing risk of SCCHN in a variant allele
      dose-dependent manner, and the decreasing trend in OR was statistically
      significant, particularly for the combined genotypes (Ptrend<0.001). These data
      suggest that the VDR f and t alleles and their genotypes may protect against
      SCCHN. However, further studies are warranted to confirm these findings.

PMID- 15861041
TI  - GSTM1, GSTT1 and CYP1A1 detoxification gene polymorphisms and their relationship
      with advanced stages of endometriosis in South Indian women.
AB  - OBJECTIVE(S): Studies on association between endometriosis and various phase I
      and phase II detoxification genes such as glutathione S-transferase M1 and theta
      1 (GSTM1 and GSTT1) and cytochrome P450 (CYP1A1) have produced inconsistent
      results possibly because of ethnic differences. The present study was undertaken
      to investigate the frequency of the CYP1A1 (6235T>C) polymorphism and GSTM1,
      GSTT1 null mutations in a South Indian women's population with and without
      endometriosis. METHODS: The frequencies of variants were studied in 310 women
      with laparoscopically proven endometriosis (rAFS III=101; IV=209) and 215 women
      without endometriosis using the polymerase chain reaction-restriction fragment
      length polymorphism method. RESULTS: The GSTM1 null deletion showed significant
      association (P=0.028) with endometriosis. No significant difference was found in
      the frequencies of the GSTT1 null deletion in cases and controls. The frequencies
      of the variant CYP1A1 homozygous and heterozygous alleles in the cases were 9%
      and 44.2% against 14.4% and 42.3% in the controls. Further, we observed a
      considerable difference in the GSTM1 null deletion frequency in this population
      when compared with other populations of the world. CONCLUSIONS: We observed an
      association between endometriosis and the GSTM1 null deletion, but not with GSTT1
      null deletions or the CYP1A1 MspI polymorphism in South Indian women.

PMID- 15861042
TI  - Identification and functional characterization of variants in human concentrative
      nucleoside transporter 3, hCNT3 (SLC28A3), arising from single nucleotide
      polymorphisms in coding regions of the hCNT3 gene.
AB  - INTRODUCTION: Human concentrative nucleoside transporter 3, hCNT3 (SLC28A3),
      which mediates transport of purine and pyrimidine nucleosides and a variety of
      antiviral and anticancer nucleoside drugs, was investigated to determine if there
      are single nucleotide polymorphisms in the coding regions of the hCNT3 gene.
      METHODS AND RESULTS: Ninety-six DNA samples from Caucasians (Coriell Panel) were
      sequenced and sixteen variants in exons and flanking intronic regions were
      identified, of which five were coding variants; three of these were non
      synonymous (S5N, L131F, Y513F) and were further investigated for functional
      alterations of the resulting recombinant proteins in Saccharomyces cerevisiae and
      Xenopus laevis oocytes. In yeast, immunostaining and fluorescence quantitation of
      the reference (wild-type) and variant CNT3 proteins showed similar levels of
      expression. Kinetic studies were undertaken in yeast with a high through-put semi
      automated assay process; reference hCNT3 exhibited Km values of 1.7+/-0.3, 3.6+/
      1.3, 2.2+/-0.7, and 2.1+/-0.6 muM and Vmax values of 1402+/-286, 1310+/-113,
      1020+/-44, and 1740+/-114 pmol/mg/min, respectively, for uridine, cytidine,
      adenosine and inosine. Similar Km and Vmax values were obtained for the three
      variant proteins assayed in yeast under identical conditions. All of the
      characterized hCNT3 variants produced in oocytes retained sodium and proton
      dependence of uridine transport based on measurements of radioisotope flux and
      two-electrode voltage-clamp studies. CONCLUSION: These results suggested a high
      degree of conservation of function for hCNT3 in the Caucasian population.

PMID- 15861043
TI  - Coumarins are competitive inhibitors of cytochrome P450 1B1, with equal potency
      for allelic variants.
AB  - OBJECTIVES: Coumarins are naturally occurring chemicals with potential as
      chemopreventive agents, several with known action on the cytochrome P450 1A
      family. We examined whether cytochrome P450 1B1 (CYP1B1) was inhibited by
      coumarins, whether such inhibition was competitive, and whether inhibition varied
      between common polymorphic variants of this enzyme. METHODS: We tested the
      inhibition properties of four coumarins, bergamottin, isopimpinellin,
      isoimperatorin, and imperatorin in an assay for oxidation of (-)benzo[a]pyrene-7R
      trans-7,8-dihyrodiol (B[a]P-7,8-diol) by CYP1B1 using yeast-microsome expressed
      enzymes. These assays were performed with wild-type enzyme and five single-amino
      acid polymorphic variants. RESULTS: All four coumarins are competitive inhibitors
      of CYP1B1, with Ki values equal to 587, 11, 6 and 1 muM respectively. Inhibition
      parameters were consistent between five haplotypes of CYP1B1, three representing
      common haplotypes in Asians, African-Americans and European-Americans, and two
      with baseline kinetic parameters previously shown to be potentially different
      from wild-type. CONCLUSIONS: Coumarins are capable of inhibiting carcinogen
      activation by CYP1B1 with varying potencies, and their efficacy as
      chemopreventive agents is not likely to be affected by polymorphism in this
      enzyme.

PMID- 15861044
TI  - Ethnic variation in CYP2A6*7, CYP2A6*8 and CYP2A6*10 as assessed with a novel
      haplotyping method.
AB  - Cytochrome P450 2A6 is the main human nicotine metabolizing enzyme coded for by a
      highly polymorphic gene, CYP2A6. CYP2A6*7, CYP2A6*8 and CYP2A6*10 are variant
      alleles common to Asian ethnicities. The CYP2A6*7 and CYP2A6*8 alleles each
      contain a non-synonymous single nucleotide polymorphism (SNP) 6558T>C and
      6600G>T, respectively, whereas the CYP2A6*10 haplotype allele contains both. We
      have developed the first haplotyping assay; it can unambiguously distinguish the
      CYP2A6*7, CYP2A6*8 and CYP2A6*10 alleles. The allele frequencies of these three
      variants were assessed using the novel haplotyping assay in Chinese-Canadian
      (n=112), Chinese-American (n=221), Taiwanese (n=319), Korean-American (n=207) and
      Japanese-Canadian (n=64) populations, as well as in Caucasian (n=110) and African
      Canadian (n=113) populations. Our new method demonstrated higher frequencies of
      CYP2A6*7 and CYP2A6*10, and a lower frequency of CYP2A6*8 in Asian populations,
      but no significant change of allele frequencies in Caucasian or African-Canadian
      populations.

PMID- 15861045
TI  - Management of frontal sinus fractures.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: 1. Understand the radiographic and clinical diagnosis of frontal sinus
      fractures. 2. Identify various management approaches to the frontal sinus
      fracture and the indications for each. 3. Understand the rationale behind the
      decision of sinus obliteration when needed. 4. Recognize the most common
      complications arising from frontal sinus fracture treatment and the methods of
      avoiding or managing these complications. SUMMARY: Frontal sinus fracture
      management is still controversial and involves preserving function when feasible
      or obliterating the sinus and duct, depending on the fracture pattern. There is
      no single algorithm for the choice of management, but appropriate treatment
      depends on an accurate diagnosis using physical examination, computed tomography
      data, and the findings of intraoperative exploration. The amount and location of
      fixation and the need for frontonasal duct and sinus obliteration or elimination
      of the entire sinus depend on the anatomy of the fracture in general and the
      extent of involvement of the anterior wall of the sinus, the frontonasal duct,
      and the posterior wall in particular. This article discusses an algorithm for
      frontal sinus fractures that was obtained from the literature and modified
      according to the authors' experience. The decision-making process presented by
      the authors has withstood the test of time over a period of more than 20 years in
      their practice and has been proven to be safe and efficacious in treating frontal
      sinus fractures of all types.

PMID- 15861047
TI  - Organization and microscopic anatomy of the adult human facial nerve: anatomical
      and histological basis for surgery.
AB  - BACKGROUND: Despite the progress in microsurgical repair of the facial nerve, the
      results remain unpredictable and the structural anatomy of the facial nerve
      poorly understood. The aim of this study was to show how the connective tissue
      and the nerve fibers are distributed in a serial cross-section of the facial
      nerve from its origin to its termination. METHODS: Sixty facial nerves from 30
      embalmed adult human cadavers were dissected for micro-anatomic study. The facial
      nerves were serially sectioned every 2 mm from the apparent origin and were
      prepared for light microscopy study. The endoneural fascicular arrangement was
      observed, the number of myelinated fibers was counted, and connective tissue was
      explored. RESULTS: There was an absence of real fascicular organization of the
      facial nerve in the pontocerebellar cistern and in the internal acoustic meatus.
      The real fascicular organization with perineurium and epineurium appeared from
      the geniculate ganglion. The number of fascicles increased in a proximo-distal
      way, and their diameter diminished. In the extratemporal part, some nerves had a
      low number of fascicles (two to six), and others had a high number of fascicles
      (seven to 15). The number of fascicles changed along the course of the facial
      nerve, especially in the extratemporal part. CONCLUSIONS: The truly fascicular
      structure appeared after the geniculate ganglion, and the rate of connective
      tissue progressed in a proximo-distal way. The high numbers of fascicles and the
      great structural variability of each facial nerve segment constitute a difficulty
      in nerve repair.

PMID- 15861048
TI  - The phenomenon of the late recovered Bell's palsy: treatment options to improve
      facial symmetry.
AB  - BACKGROUND: Bell's palsy is an idiopathic neuropathy of cranial nerve VII, and
      the incidence ranges from 15 to 40 per 100,000. The majority of patients recover,
      but up to 16 percent of patients have significant sequelae. The phenomenon of the
      "late recovered" Bell's palsy has the following specific features and has not
      formerly been described: (1) tightening of the facial muscles, with a deepening
      nasolabial fold and reduced palpebral fissure; (2) blepharospasm; and (3)
      incomplete recovery of peripheral VIIth nerve branches, with ipsilateral forehead
      paralysis, reduced depressor anguli oris function, and poor excursion of the
      angle of the mouth on smiling. METHODS: Nonsurgical treatment involved four
      monthly botulinum toxin injections. Patients had injections to paralyze the
      ipsilateral orbicularis oculi, contralateral forehead rhytides, and depressor
      anguli oris and to treat blepharospasm and muscle tightness. The effectiveness of
      the botulinum toxin injections on facial symmetry and patient appreciation of
      this were assessed by measuring brow height and teeth exposure before and 3 weeks
      after injection. RESULTS: Twenty-three patients were followed up for a mean
      period of 37 months. The difference in brow height and teeth exposure after
      injection was less than preinjection measurements, but this did not reach
      statistical significance. Patient self-assessments showed improvements in their
      appreciation of the facial symmetry, ability to go out in public, and feelings of
      self-worth (visual analogue scale). Surgical treatment options include
      ipsilateral brow lift, division of the contralateral frontal branch,
      contralateral tarsorrhaphy to equalize the palpebral fissures, and bilateral
      upper blepharoplasty. CONCLUSIONS: The true benefit of botulinum toxin injections
      was more apparent during facial animation and not when the face was static. The
      patients greatly appreciated the improvement in facial symmetry. Various
      treatment options are available to improve the quality of life for patients with
      late recovered Bell's palsy.

PMID- 15861049
TI  - Cortical adaptation to restoration of smiling after free muscle transfer
      innervated by the nerve to the masseter.
AB  - BACKGROUND: The child with Mobius syndrome presenting for facial reanimation
      presents a difficult challenge. When bilateral paralysis and paresis preclude use
      of the contralateral facial nerve, the authors' preferred donor nerve for
      reinnervation of free muscle transfer is a branch of the trigeminal nerve, the
      ipsilateral nerve to the masseter. METHODS: The authors have used a branch of the
      trigeminal nerve as a donor for three children with Mobius syndrome. RESULTS: Of
      three children with Mobius syndrome, two are now able to smile independently of
      jaw closure. One child is now 2.6 years past bilateral free gracilis transfers
      completed at age 13.2 years. The second child is 8.2 years past free gracilis
      transfer to the left side of the face performed at age 7.6 years. The third child
      is 5.6 years past bilateral facial reanimation with free latissimus and free
      gracilis flaps completed at age 13.4 years. This child is not able to smile
      independently of jaw closure. The two who are able to smile independently of jaw
      closure demonstrated maximum excursion of the lateral commissure on the affected
      sides when asked to smile without biting; however, they demonstrated minimal
      excursion of the lateral commissure on the affected sides when asked to bite
      without trying to smile. CONCLUSIONS: These findings indicate that smiling
      independently of jaw closure is attainable with reanimation to the masseteric
      branch, refuting previous speculations. Early age at operation and absence of
      complete bilateral paralysis in these two children may have contributed to
      cortical adaptation to smiling.

PMID- 15861051
TI  - Timing of cleft palate closure should be based on the ratio of the area of the
      cleft to that of the palatal segments and not on age alone.
AB  - BACKGROUND: Retrospective and prospective serial spatiotemporal investigations
      were carried out primarily to determine whether the ratio of the size of the
      posterior cleft space relative to the palatal surface area limited laterally by
      the alveolar ridges can be used to select the appropriate time for surgical
      closure of the palatal cleft space. Two subsamples were compared to determine
      whether the size of the palate and velocity of palatal development in well
      growing cases differ from those in cases treated by vomer flap surgery. The
      prospective investigation asked whether presurgical orthopedics increases the
      rate of palatal growth and palatal size. METHODS: Using the palatal casts of 242
      male and female individuals from eight institutions in the United States and
      Western Europe that followed a variety of treatment protocols, separate serial
      analyses were conducted of well growing cases with excellent aesthetics, dental
      occlusion, and speech and a control series of 17 cases of various clefts of the
      lip and alveolus and/or soft palate but no clefts in the hard palate. Twelve
      groupings of cases were established depending on their institutional location and
      type of cleft. RESULTS: Among the various institutions in the study, palatal
      growth rates and size were statistically similar. Growth in the various clinical
      series (size, mm2) was less than that of the control series. The ratio of cleft
      space size to palatal surface area medial to the alveolar ridges was 10 percent
      or less at 18 months of age in most cases. There was no statistical difference in
      total surface size between groups, except for one series whose total growth size
      was least of all. Right and left lateral palatal segments, whether large or
      small, grew at the same rate. The sample of bilateral cases was too small for
      statistical comparisons. Presurgical orthopedics did not stimulate palatal
      growth. The coefficient of variance was less than 10 percent in all measurements.
      CONCLUSIONS: Delaying all cleft closure surgery until 5 years of age and older is
      unnecessary to maximize palatal growth. The best time to close the palatal cleft
      space is when the palatal cleft size is 10 percent or less of the total palatal
      surface area bounded laterally by the alveolar ridges. The 10 percent ratio
      generally occurs between 18 and 24 months but can occur earlier or later. There
      is more than one good type of palatal cleft closure surgery.

PMID- 15861052
TI  - Retrospective study of 1251 maxillofacial fractures in children and adolescents.
AB  - BACKGROUND: Fractures of the facial skeleton are relatively uncommon in children
      and adolescents, and only a few reports review a significant number of patients.
      The authors performed a retrospective study to analyze the different
      characteristics of such fractures in the pediatric population of Portugal.
      METHODS: The authors reviewed the clinical records of a series of 912 patients 18
      years of age or younger with facial fractures treated by the Departments of
      Plastic, Reconstructive, and Aesthetic Surgery and of Maxillofacial Surgery, Sao
      Joao Hospital, in Porto, Portugal, between the years 1993 and 2002. The following
      parameters were evaluated: age; sex; cause of accident; hour, day, and month of
      hospital admission; location and type of fractures; presence and location of
      associated injuries; treatment methods; length of in-hospital stay; and
      complications. RESULTS: A total of 1251 fractures were treated. The ratio of boys
      to girls was 3.1:1. Patients between 16 and 18 years old were the major group
      (47.8 percent). Motor vehicle accident was the most common cause of injury (53.3
      percent of patients). Mandibular fracture was the most common type of fracture
      (48.8 percent). Associated injuries occurred in 558 patients (64.5 percent).
      CONCLUSIONS: Pediatric facial fractures are usually associated with severe
      trauma. The number of fractures caused by automobile accidents has decreased (p <
      0.05). The incidence of this type of fracture is high in Portugal.

PMID- 15861053
TI  - Maxillofacial morphology in children with complete unilateral cleft lip and
      palate treated by one-stage simultaneous repair.
AB  - BACKGROUND: There is a common belief among the majority of surgeons occupied with
      cleft lip-cleft palate repair that early one-stage simultaneous repair of hard
      and soft palates affects maxillofacial development adversely. This proposition
      has not been proven with long-term clinical studies. In this study, the effects
      of one-stage repair on the maxillofacial development of children with complete
      unilateral cleft lip-cleft palate were investigated, and the results were
      compared with those of the cleft children treated with conventional two-stage
      repair. METHODS: The study was designed as follows. Group 1 consisted of 19
      children (mean age, 85.4 +/- 12.8 months) treated with a one-stage procedure. In
      this group, cleft lip, palate, and alveolus were repaired simultaneously at a
      single surgical session in the first 10 months of life (mean age at time of
      surgery, 6.8 +/- 1.2 months). Group 2 consisted of 22 children (mean age, 90.1 +/
      13.0 months) treated in two stages as follows: lip repair was performed at a
      mean age of 4.8 +/- 1.0 months and palate repair was performed at a mean age of
      14.6 +/- 2.0 months. The follow-up period was approximately 6.3 years for both
      study groups. Group 3 (control) consisted of 27 children (mean age, 87.1 +/- 11.7
      months) without cleft who were matched for age. RESULTS: Compared with the
      control group, the children in both cleft groups revealed a greater
      maxillomandibular retrognathism, a more open palatal plane, larger anterior
      facial heights, and decreased posterior vertical maxillofacial heights. No
      significant difference was determined between study groups 1 and 2. CONCLUSIONS:
      Because both of the surgical treatment procedures give rise to similar
      maxillofacial development outcomes, regardless of the timing of surgery, the one
      stage procedure offers several important advantages, such as less psychosocial
      trauma, low cost, and possibly an improvement in speech results because of less
      scarred palatal fields and the low rate of palatal fistula.

PMID- 15861054
TI  - Early development of infants with untreated metopic craniosynostosis.
AB  - BACKGROUND: The purpose of this archival descriptive study was to examine the
      associations among craniosynostosis, perinatal risk factors or complications, and
      early cognitive development in infants diagnosed with craniosynostosis before
      they underwent surgery, to provide a greater empirical basis for surgical
      decision making and other early interventions. Specifically, it was hypothesized
      that there would be a greater number of infants with developmental delays than
      seen in the normative population. Furthermore, it was hypothesized that greater
      severity of synostosis would be correlated with lower cognitive and developmental
      scores. The secondary purpose of this study was to examine specific developmental
      domains such as language and motor skills in children with metopic
      craniosynostosis. METHODS: The research subjects for this retrospective cross
      sectional study were a consecutive series of 22 infants diagnosed with metopic
      synostosis: 86 percent male, ages 3.6 to 25.3 months (mean +/- SD, 10.6 +/- 6.4
      months). Mean gestational age was 38.8 (2.3) months, mean birth weight was 107.7
      ounces, and 48.1 percent subsequently had craniovault reconstruction. Severity of
      craniosynostosis was assessed by a plastic surgeon (Buchman) and a neurosurgeon
      (Muraszko) and was confirmed radiographically by an independent rater
      (Angobaldo). Cognitive status was assessed with the Bayley Scales of Infant
      Development, Second Edition, at a mean age 11.6 (4.8) months. RESULTS: The mean
      Mental Development Index score for the sample was 96.0 (14.5), falling within the
      average range. Severity of synostosis was not significantly correlated with the
      overall Mental Development Index score. The mean language quotient for the sample
      was 77.3 (21.1). CONCLUSIONS: Despite suspicions that increased severity of
      deformity in infants with metopic craniosynostosis correlates with decreased
      cognitive and motor development, no such associations could be demonstrated. The
      results of this study did suggest, however, that children with isolated metopic
      craniosynostosis might show specific developmental delays in language
      acquisition. Finally, there were no significant correlations between cognitive
      development and prenatal risk factors.

PMID- 15861055
TI  - Halo distraction of the Le Fort III in syndromic craniosynostosis: a long-term
      assessment.
AB  - BACKGROUND: Little is known about long-term outcomes after Le Fort III halo
      distraction, such as indications for distraction, amount of relapse, and long
      term maxillary growth. METHODS: During a 5-year period, 51 Le Fort III
      osteotomies were performed; 41 of these were by halo distraction for the
      treatment of craniofacial dysostosis (Apert syndrome, 25; Crouzon syndrome, nine;
      Pfeiffer syndrome, four; other, three). Patient records were reviewed and 104
      cephalograms were analyzed. RESULTS: The average treatment age was 8 years, and
      the average hospitalization was 5.3 days (3.6 days for the second half of this
      series). The average distraction was 26 mm (range, 14 to 44 mm), the sella-nasion
      subspinale angle increased from 70 degrees to 87 degrees, the upper incisal edge
      advanced 18 mm, and the vertical distance between nasion and point A increased by
      7 mm. There was no maxillary relapse at 1 year and no measurable forward
      maxillary growth for up to 5 years, although the maxilla did grow vertically (p <
      or = 0.001). Three patients underwent tracheostomy removal; sleep studies showed
      the average respiratory disturbance index improved from 24 to 11 (p = 0.004) and
      the minimum oxygen saturation increased from 81 to 89 (p = 0.006). Three early
      patients had incomplete advancements. CONCLUSIONS: The maxilla remained stable
      after Le Fort III halo distraction without any relapse, and no anterior growth
      was observed up to 5 years postoperatively. This procedure effectively eliminated
      sleep apnea in most children, and had a low overall complication rate that
      declined with experience. Most distracted patients will likely avoid the
      traditional second Le Fort III.

PMID- 15861056
TI  - Hypertelorism: the importance of three-dimensional imaging and trends in the
      surgical correction by facial bipartition.
AB  - BACKGROUND: The technique of facial bipartition has been considered a great
      advance in achieving a more natural appearance in hypertelorism correction.
      METHODS: Fourteen patients who had undergone hypertelorism correction by facial
      bipartition were retrospectively studied to analyze the role of three-dimensional
      computed tomographic reconstruction in the evaluation of the deformity and
      preoperative planning. The procedure and surgical details that can improve the
      outcome were described. A reproducible set of three-dimensional measurements that
      can help in preoperative patient evaluation was determined based on information
      obtained using the Analyze/AVW 3.1 system (Biomedical Imaging Resource, Mayo
      Foundation, Rochester, Minn.). RESULTS: In this series, the most common diagnosis
      was frontonasal dysplasia (64.3 percent). Five patients had second-degree (35.7
      percent) and nine had third-degree hypertelorism (64.3 percent). The three
      dimensional scans were shown to be highly accurate in predicting the degree of
      deformity. There was a significant difference in the preoperative and
      postoperative interdacryon distance and midface height (p < 0.05) but not in the
      bitemporal distance (p = 0.08). The simulation correlated significantly with the
      postoperative result when interdacryon distance and midface height were analyzed
      (0.736 and 0.999). CONCLUSIONS: Facial bipartition provided a three-dimensional
      correction of hypertelorism. Three-dimensional imaging can definitely be
      considered an extra tool for accurate surgical planning and helping the family
      understand the surgical procedure and the end result.

PMID- 15861057
TI  - Arterial blood flow changes after free tissue transfer in head and neck
      reconstruction.
AB  - BACKGROUND: The authors measured pedicle arterial flow volume output using color
      Doppler ultrasonography in 23 patients after free tissue transfer in head and
      neck reconstruction. METHODS: Transferred flaps included six free jejunums, eight
      free radial forearm flaps, and four anterolateral thigh flaps. Flow volume output
      could be measured on all patients and was selectively measured in 17 patients
      with color Doppler ultrasonography on days 1, 4, 7, 14, 21, and 28 after surgery.
      The authors compared output change in different periods. In addition, they
      compared flow volume output on the first postoperative day in the different flaps
      and in the different recipient arteries and veins, and the effectiveness of
      irradiation in the different patients. RESULTS: Three of the 17 patients
      developed venous thrombosis. Flow volume output on the skin flaps increased
      gradually from day 1 to 7 after surgery and decreased gradually until day 28 in
      14 patients without venous thrombosis. The free jejunum had more pedicle arterial
      blood flow than the skin flaps and it showed minimal flow volume output change.
      There were no significant differences among different recipient vessels or
      different skin flaps, or in the effectiveness of irradiation in the different
      patients. Three patients who developed venous thrombosis were salvaged by
      reanastomoses of the thrombosed vein. CONCLUSIONS: Before reanastomosis, abnormal
      arterial waveform, decreasing flow volume output, and a lack of venous blood flow
      were observed in the patients who developed venous thrombosis. After
      reanastomoses, the output was significantly improved and the flaps survived
      completely in all three cases. The authors conclude that color Doppler
      ultrasonography is useful for detecting venous thromboses too.

PMID- 15861058
TI  - Selection of recipient vessels in double free-flap reconstruction of composite
      head and neck defects.
AB  - BACKGROUND: Massive defects of the head and neck regions after resection of
      advanced carcinoma often require two flaps for optimal reconstruction. This study
      focuses on the selection of proper recipient vessels. METHODS: A total of 262
      free-flap transfers were performed in 130 patients using the two-flap approach
      (one patient received two flaps twice). RESULTS: For microvascular anastomosis of
      inner flaps (intraoral lining-bone reconstruction flaps), the ipsilateral facial
      artery was used in 56 flaps (42.8 percent), the ipsilateral superior thyroid
      artery was used in 49 flaps (37.4 percent), and a branch of the internal jugular
      vein was used as recipient vein in 101 flaps (77.1 percent). For external flaps
      (soft-tissue-external skin reconstruction flaps), the ipsilateral superior
      thyroid artery was used in 59 flaps (50.4 percent) and the transverse cervical
      artery was used in 19 flaps (16.2 percent). In 14 patients the inner flaps
      provided distal run-off for external flap revascularization. Only seven flaps
      required vein grafts; they were all used for external face reconstruction (2.8
      percent). There were six total (2.3 percent) and 12 partial (4.6 percent) flap
      failures. CONCLUSIONS: Recipient vessel selection and preparation in primary head
      and neck cancer reconstruction requiring two simultaneous flaps should take into
      consideration (1) avoidance of unnecessary destruction during tumor ablations and
      preservation of as many neck vessels as possible, (2) length and diameter match
      between flap pedicles and recipient vessels to avoid vein grafts, and (3)
      possible need of another free-flap reconstruction for flap failure, complication,
      recurrence, or secondary primary cancers. The previously radiated or operated
      neck does not preclude the use of recipient vessels from that side. Distal run
      off of the inner flap for external flap revascularization should be avoided if
      possible. Once those principles are observed, two-flap reconstruction for primary
      cancer presents no more difficulties than single-flap reconstruction.

PMID- 15861059
TI  - Maxillary reconstruction with the free fibula flap.
AB  - BACKGROUND: The objective of this study was to evaluate the outcomes of using the
      free fibula flap in the reconstruction of maxillary defects. METHODS: Thirty-four
      consecutive cases of maxillary reconstruction with the free fibula flap were
      reviewed. All clinical data were analyzed, including primary diseases, types of
      maxillary defect, free fibula flap design, perioperative complications, and
      follow-up results. The main postoperative functional indices, including oral
      diet, speech, type of dental restoration, and aesthetic results, were evaluated.
      RESULTS: Of the 34 patients who underwent maxillary reconstruction with the free
      fibula flap, the primary diseases were malignant tumor in 20 patients, benign
      tumor in 11 patients, and trauma in three patients. Free fibula flap transfer was
      successful in all cases. Postoperative complications occurred in five patients.
      Recipient-site wound infection occurred in two patients and donor-site wound
      dehiscence occurred in three patients. One patient with donor-site wound
      dehiscence had postoperative lameness. The oral and nasal cavities were separated
      well by the flap in all patients. The patients were able to take food orally and
      had no problems with speech intelligibility. Osseointegrated implants were placed
      in four patients, and complete conventional prostheses were applied in 19
      patients. Excellent cosmetic results were obtained in 22 patients. CONCLUSIONS:
      Alveolar arch defects can be reconstructed successfully using free fibula flaps.
      This procedure also allows for dental implant rehabilitation, which can improve
      the patient's appearance and oral function and enhance the overall quality of
      life. The fibula free flap transfer has a high success rate and low perioperative
      complication rate, making it an ideal choice for maxillary defect reconstruction.

PMID- 15861060
TI  - Surgical correction of cryptotia with V-Y advancement of a temporal triangular
      flap.
AB  - BACKGROUND: A new approach is introduced for the correction of cryptotia using a
      large triangular flap designed on the temporal scalp and skin over the auricle.
      METHODS: The posterior limb of the triangular flap was continued to the mastoid
      area at the midportion of the auricle. The abnormal insertion of the auricular
      intrinsic muscles was detached. A sharply curved antihelical crus or a
      contraction of helical cartilage was corrected. After ample skin was provided to
      maintain the auriculocephalic sulcus by inferior advancement of the flap, the
      donor site was closed primarily. RESULTS: From 1999 to 2003, a total of 13 cases
      of 11 patients with cryptotia were treated. Nine patients had unilateral
      cryptotia and two had bilateral cryptotia. The follow-up period was 3 months to 1
      year, with relatively favorable results. The length of the helix was extended,
      and it was possible to increase the width of the upper third of the auricle.
      There were no postoperative complications, such as necrosis or flap infection.
      CONCLUSIONS: The main advantages of this proposed technique are simple and easy
      design, provision of enough skin to the upper and posterior portions of the
      auricle, sufficient depth of the auriculocephalic sulcus, correction of cartilage
      deformities with unrestricted access, and no additional skin grafting. Problems
      encountered were the development of a visible scar on the donor site and lowered
      hairline because of advancement of the temporal triangular flap.

PMID- 15861061
TI  - Geometric analysis of the V-Y advancement flap and its clinical applications.
AB  - BACKGROUND: Geometry is fundamental in the comprehension of local flap design.
      The purpose of this study was to discuss the differences between the V-Y
      advancement flap and other local flaps, understand its geometry, and analyze its
      clinical applications. METHODS: The analysis was based on qualitative
      measurements of an injury, taking into consideration the following dimensions:
      largest diameter, shortest diameter, and depth. Standardization of the flap
      design consisted of directing its advancement over the shortest diameter and
      making the V base match the size of the largest diameter. The flap was analyzed
      in two planes: the horizontal plane includes the V-Y design and the vertical
      plane includes the flap pedicle. The height of the flap can be obtained by simple
      trigonometry, taking into consideration the largest diameter and alpha angle in
      the horizontal plane. In the vertical plane, where the pedicle and pivot plane
      are positioned, for known shortest diameter and depth, the final depth of the
      pivot plane can be calculated using Pythagoras' principles. RESULTS: This
      analysis was applied to 25 patients with adequate skin coverage at follow-up. A
      correction factor was added to reduce the overdeepening of the vertical plane
      calculations. The final concepts for clinical application in the classic deep
      pedicle V-Y flap design are to calculate the length of the V by modifying the
      alpha angle and to move the pivot plane deeper to accomplish optimal flap
      movement. CONCLUSIONS: Using these principles, tension-free closure of the Y and
      appropriate advancement of the flap are obtained.

PMID- 15861062
TI  - The single and double-folded supraclavicular island flap as a new therapy option
      in the treatment of large facial defects in noma patients.
AB  - BACKGROUND: Noma is a disfiguring disease requiring a complex therapeutic
      strategy involving a range of approaches, from skin grafts to local flaps,
      pedicled flaps, and free flaps. The surgeon must adapt his or her choice of
      therapy to the patient and, especially in the Third World, to local healthcare
      environments. METHODS: The authors describe 10 case reports from a stay at the
      Noma Children's Hospital, in Sokoto, Nigeria, where they used the supraclavicular
      island flap as a new therapy option for the reconstruction of large facial
      defects resulting from noma infection. In combination with local mucosa or skin
      grafts, the supraclavicular island flap was used as an outer lining and also, in
      three cases, as an inner lining in the form of a double-folded flap. RESULTS: The
      authors were able to use a pedicled supraclavicular island flap to cover defects
      as large as half of the face. All 10 pedicled supraclavicular island flaps
      survived; the only exception was a partial flap necrosis resulting from incorrect
      application of a wound dressing that kinked the pedicle of the flap. CONCLUSIONS:
      The authors recommend consideration of the supraclavicular island flap in
      combination with mucosal or skin grafts as a reliable and safe option for
      covering most facial defects in noma patients. Because of its simplicity and
      reliability, this flap replaced the deltopectoral flap and the latissimus dorsi
      flap as "workhorses," actually reducing the indication for free flaps to the face
      in cases of large full-size defects. Double folding the supraclavicular island
      flap is possible, but further clinical studies are needed.

PMID- 15861063
TI  - Analysis of breast reduction complications derived from the BRAVO study.
AB  - BACKGROUND: Analysis of complication data derived from the Breast Reduction
      Assessment: Value and Outcomes (BRAVO) study, a 9-month prospective, multicenter
      trial, is presented. METHODS: Data derived from 179 patients were analyzed,
      including bivariate associations between complications and single predictor
      variables (Fisher's exact test or chi-square testing) or continuous variables
      (two-sample t test) and, finally, logistic regression. RESULTS: The overall
      complication rate was 43 percent (77 patients). Simple, bivariate analysis linked
      preoperative breast volume, shoulder strap grooving, and a vertical incision with
      an increased incidence of complications (p < 0.05, 0.02, and 0.02, respectively).
      Delayed wound healing, the most common complication, correlated directly with
      average preoperative breast volume (p < 0.045), average resection weight/breast
      (p < 0.027), and smoking (p < 0.029) and inversely with age (p < 0.011). Vertical
      incision techniques were associated with an increased complication frequency (p <
      0.05) without a link to specific complications. Logistic regression analysis
      associated resection weight as the sole variable for increased risk of
      complications (p = 0.05) and with absolute number of complications [mean
      resection weight of 791 g for patients without complications versus 847, 882, and
      1752 g for patients with one, two, and three complications, respectively (p =
      0.0022)]. Each 10-fold increase in resection weight increased the risk of
      complication 4.8 times and increased the risk of delayed healing 11.6 times.
      CONCLUSIONS: Complication data revealed several significant features: (1)
      resection weight correlated with increased risk and absolute number of
      complications; (2) delayed healing correlated directly with resection weight and
      inversely with increasing age, anesthesia times, and preoperative Short Form-36
      bodily pain score; (3) a vertical incision may be associated with increased
      incidence of complications but requires further analysis; and most importantly,
      (4) the presence of complications had no negative effect on improvement in Short
      Form-36 and Multidimensional Body-Self Relations Questionnaire scores.

PMID- 15861064
TI  - Soft fluted silicone drains: a prospective, randomized, patient-controlled study.
AB  - BACKGROUND: For some patients, removal of surgical drains can be the most painful
      part of surgery. The authors present a prospective, randomized, patient
      controlled study comparing soft fluted silicone (Blake) drains with conventional
      rigid (Portavac) drains. METHODS: After ethical committee approval, 43 patients
      undergoing bilateral breast reduction surgery were recruited into the study. A
      Blake drain was inserted on one side and a Portavac drain was inserted on the
      contralateral side; the patients therefore acted as their own controls. Pain
      scores were measured on a descriptive scale 10 minutes before, during, and 10
      minutes after drain removal. Statistical analysis was carried out using the
      Wilcoxon signed ranks matched pairs test. RESULTS: The results show that Blake
      drains are less painful before (p = 0.05), during (p = 0.01), and after removal
      (p = 0.009). Of those patients who expressed a preference, 27 preferred the Blake
      drain and 10 preferred the Portavac drain. CONCLUSION: The authors advocate the
      use of a silicone fluted (Blake) drain for any wound requiring drainage,
      especially if large-caliber drains are indicated.

PMID- 15861065
TI  - Spaghetti wrist trauma: functional recovery, return to work, and psychological
      effects.
AB  - BACKGROUND: Few studies on spaghetti wrist trauma have been published. The study
      populations have all consisted of small numbers of patients, and most studies
      have focused on functional recovery. In addition, different definitions of this
      injury have been used. The objective of this study was to assess outcome for a
      larger group of patients in terms of functional recovery, return to work
      potential, and psychological distress, and to compare outcomes between the two
      most commonly used definitions for spaghetti wrist injury. METHODS: The initial
      study-population consisted of 67 patients. Fifty patients completed a
      questionnaire package consisting of the Disabilities of Arm, Shoulder, and Hand
      questionnaire, including the Functional Symptom Score (range, 0 to 100), a
      questionnaire to evaluate return to work and time off work (range, 0 to 52), and
      the Impact of Event Scale (range, 0 to 75). Motor recovery and sensory recovery
      were assessed in an outpatient setting, on average, 10 years (range, 2 to 18)
      after the operation (n = 43). RESULTS: The mean Functional Symptom Score was 15.1
      (SD, 16.1; range, 0 to 74) after a mean follow-up of 10.0 years (SD, 4.4; range,
      2 to 18). Mean time off work was 34.7 weeks (SD, 17.9; range, 4 to 52), and 45.2
      percent of the patients could not return to work within 1 year after the injury.
      Mean score on the Impact of Event Scale was 26.2 (SD, 19.7; range, 2 to 69).
      Compared with the unaffected hand, grip and tip pinch strength were decreased
      with means of 23.5 percent (SD, 22.4; range, 0 to 93) and 33.9 percent (SD, 23.7;
      range 0 to 83), respectively. Regarding sensory recovery, 12 patients (27.9
      percent) had no protective sensation. No statistical differences were found
      between the two different definitions. CONCLUSIONS: This study demonstrated that
      spaghetti wrist injury can be placed among the severe disabling injuries.
      Comparison of the two definitions did not reveal any differences in outcome. To
      complete the evaluation of long-term outcome, a patient-derived assessment of
      function can be added to the clinical examination, and attention should be paid
      to psychological distress following the injury.

PMID- 15861066
TI  - Microvascular free flap reconstruction in pediatric lower extremity trauma: a 10
      year review.
AB  - BACKGROUND: Limb-threatening wounds of the adult distal lower extremity pose a
      challenge to the microvascular surgeon and are the subject of a sizable body of
      literature. The microsurgical management of these injuries in the pediatric
      population has some unique features but has not previously been the subject of a
      separate study. METHODS: A review was performed of all pediatric patients (<18
      years of age) who received lower extremity free flaps for trauma at the
      University of Kentucky Medical Center between 1992 and 2002. Charts were reviewed
      and patients were contacted via telephone and given a standardized questionnaire.
      Logistic regression was used to identify factors predictive of worse outcome or
      complications. RESULTS: Twenty-six patients (28 flaps) met the selection
      criteria. The most common mechanism of injury was all-terrain vehicle accidents
      (n = 6), followed by motorcycle accidents, lawnmower injuries, and gunshot
      wounds. The latissimus dorsi muscle flap was chosen in 15 cases, with four other
      muscle flaps chosen for the remaining 13 cases. There were 12 Gustillo 3B or 3C
      fractures of the tibia. External fixation was used in 10 cases and internal
      fixation was used in two. Four patients had a bone gap greater than 4 cm. Three
      were successfully treated with distraction osteogenesis. The postoperative
      complication rate was 62 percent, with infection and partial skin graft loss
      being the most common complications. Three flaps were lost. Growth disturbances
      were seen in two patients. Patients receiving free flaps within 7 days after
      injury were seen to have a statistically significant lower rate of complications
      than those undergoing the procedure beyond the first week. Follow-up ranged from
      2 to 11 years, with a mean follow-up of 4.5 years. All limbs were successfully
      salvaged, and all patients were ambulatory at the time of the survey.
      CONCLUSIONS: There is a significant role for the microvascular surgeon in the
      management of limb-threatening injuries in children. If the unique features of
      this population are taken into consideration, a high rate of limb salvage and
      good function can be expected.

PMID- 15861067
TI  - Fasciocutaneous flaps based on fascial feeder and perforator vessels for defects
      in the patellar and peripatellar regions.
AB  - BACKGROUND: Soft-tissue reconstruction in the patellar and peripatellar regions
      is a challenging problem. Restoring the original thin, pliable, and tough skin
      properties is a necessary demand, if appearance and knee function are not to be
      compromised. Local tissue provides the closest match to the original, but limited
      availability can restrict the reach of conventional local flaps and, more often
      than not, produce donor sites that need coverage of their own. METHODS: A
      retrospective study was performed over a 7-year period (from 1995 to September of
      2002) using local fasciocutaneous flaps, based on fascial feeder and perforator
      vessels, to reconstruct a variety of patellar and peripatellar defects. Fifteen
      patients with a mean age of 62 years (range, 18 to 86 years) were reviewed.
      RESULTS: Early complications were minimal, with only one patient (wound
      dehiscence) requiring a further procedure. All patients achieved a good final
      outcome. CONCLUSIONS: The authors found the fascial feeder- and perforator-based
      local fasciocutaneous flap in the patellar and peripatellar regions to be a
      simple and reproducible technique to perform. By islanding local flaps on
      perforator/fascial feeder vessels, greater mobility is achievable, when compared
      with conventional flaps. Combining local fascial feeder- and perforator-based
      flaps with V-Y advancement minimizes donor-site complications. On this basis,
      well-matched local tissue can be used for reconstruction in the patellar and
      peripatellar areas, with minimal compromise to either appearance or function or
      both.

PMID- 15861068
TI  - Tissue-engineered flexible ear-shaped cartilage.
AB  - BACKGROUND: Previous attempts to engineer human ear-shaped constructs mimicked
      human shape but lacked the flexibility and size of a human ear. Recently, the
      authors engineered flexible cartilage by incorporating a perichondrium-like layer
      into the construct. In this study, they used lyophilized swine perichondrium as a
      pseudoperichondrium, examined its ability to confer flexibility to tissue
      engineered cartilage, and used it to engineer flexible cartilage in the shape and
      size of a human ear. METHODS: Auricular chondrocytes and perichondrium were
      isolated from swine. Chondrocytes were mixed with fibrin polymer and gelled to
      form 5 x 20-mm constructs. Constructs alone (control, n = 6) or constructs
      sandwiched between two layers of lyophilized swine perichondrium (experimental, n
      = 6) were implanted into athymic mice. Auricular chondrocytes in fibrin polymer
      and lyophilized perichondrium were also used to form a tri-layer, ear-shaped
      construct, which was implanted into an athymic rat and externally stented for 6
      weeks (n = 1). At 12 weeks, constructs were analyzed with histology and gross
      mechanical testing. RESULTS: New cartilaginous tissue was engineered in both the
      experimental and control groups. In samples laminated with lyophilized swine
      perichondrium, the intimate integration of the laminate with the neocartilage
      closely resembled the histoarchitecture of the native swine ear. Experimental
      constructs had mechanical properties similar to those of the native swine ear,
      while control constructs fractured with similar testing. The engineered ear could
      not be fractured with gross mechanical testing, and its size, shape, and
      flexibility remained stable. CONCLUSIONS: This study demonstrates that it is
      possible to engineer a cartilage construct that resembles the human ear not only
      in shape but also in size and flexibility. This study also confirms that
      lamination is a reliable method to confer elastic-like flexibility to an
      engineered cartilage construct.

PMID- 15861069
TI  - Repair of the immature and mature craniofacial skeleton with a carbonated calcium
      phosphate cement: assessment of biocompatibility, osteoconductivity, and
      remodeling capacity.
AB  - BACKGROUND: The apatite compounds used most commonly in craniofacial
      reconstruction are highly crystalline and biologically inert ceramics. Because
      their capacity to be replaced by native bone is limited, they have found little
      application in repair of the growing craniofacial skeleton. Carbonated calcium
      phosphate cements more closely resemble the mineral phase of bone, thereby
      offering enhanced bioresorption and osteoconductivity, but their fate in the
      immature and mature craniofacial skeleton has not been investigated. METHODS: The
      authors hypothesized that the capacity for cell-mediated remodeling of carbonated
      calcium phosphate cements is based on (1) their crystallographic and
      compositional similarity to the mineral phase of bone and (2) the osteogenic
      capacity of the host. Four noncritical-sized calvarial defects were created in
      six 3-week-old and six 16-week-old Yorkshire pigs. The defects were repaired with
      autologous bone, sintered carbonated calcium phosphate cement disks with a higher
      crystal order, or carbonated calcium phosphate cement (Norian CRS; Synthes
      Maxillofacial, West Chester, Pa.). The fourth defect was left empty as a control.
      Specimens were harvested at 30 and 90 days postoperatively. RESULTS: Empty
      defects healed with dense fibroconnective tissue in all groups. Autologous bone
      grafts underwent complete remodeling and replacement with woven bone at both time
      points. Sintered carbonated calcium phosphate disks demonstrated no bony ingrowth
      or remodeling. In immature animals, carbonated calcium phosphate cement implants
      were progressively replaced with woven bone through osteoclast-mediated
      resorption and osteoblast-mediated bone formation. Only minimal remodeling of the
      carbonated calcium phosphate cement implants was observed in skeletally mature
      animals. CONCLUSIONS: The results of these experiments suggest that the extent of
      remodeling of carbonated calcium phosphate cement is dependent on both the
      composition of the implant itself and the osteogenic capacity of the host and
      that carbonated calcium phosphate cement may be used successfully for inlay
      applications in the immature craniofacial skeleton.

PMID- 15861070
TI  - The vascular basis of perforator flaps based on the source arteries of the
      lateral lumbar region.
AB  - BACKGROUND: Perforator flaps based on the integument of the trunk have been well
      described in the literature; however, the anatomy of many donor sites has yet to
      be adequately documented. The integument of the lateral lumbar region of the
      trunk is supplied by a number of source arteries (lower posterior intercostal,
      lumbar, superior epigastric, deep inferior epigastric, superficial inferior
      epigastric, superficial circumflex iliac, deep circumflex iliac) whose large
      perforators may be suitable for perforator flap harvest. The purpose of the
      current study was to describe the vascular anatomy of these perforators in the
      lateral lumbar region. METHODS: A series of five fresh human cadavers were
      studied using a lead oxide-gelatin injection technique. The integument of the
      trunk (10 sides or hemitrunk specimens) was dissected, and the perforating
      vessels (diameter > or =0.5 mm) were identified, noting vascular origin,
      diameter, and pedicle length. Radiographs of tissue specimens were digitally
      analyzed using the software Scion Image for Windows (Scion Corp., Frederick, Md.)
      to determine vascular territories. RESULTS: The source vessels contributed a
      summed mean of 33 perforators per hemitrunk, with a mean emerging vessel diameter
      of 0.7 +/- 0.2 mm and a corresponding mean superficial pedicle length of 31 +/-
      24 mm. The total area of skin supplied directly by these 33 perforators was 1200
      cm2, equating to a mean area of 37 cm2 per perforator. CONCLUSION: The authors
      have comprehensively described the anatomy of perforators of the lateral lumbar
      region of the trunk.

PMID- 15861071
TI  - The posterior neuromuscular compartment of the deltoid.
AB  - BACKGROUND: The aim of this study was to define a posterior neuromuscular
      compartment of the deltoid with adequate innervation and circulation for use as a
      local transposition flap as well as a functional flap to restore shoulder and
      elbow function. METHODS: The nerve supply and blood supply to the posterior one
      third of the deltoid was studied in 20 cadaveric shoulders. RESULTS: A posterior
      neuromuscular compartment of the deltoid with adequate circulation and
      innervation was identified. It was feasible to transpose it for local coverage
      about the shoulder and to restore shoulder abduction and elbow extension.
      CONCLUSION: A posterior neuromuscular functional compartment of the deltoid has
      been identified.

PMID- 15861072
TI  - Tissue-engineered bone from BMP-2-transduced stem cells derived from human fat.
AB  - BACKGROUND: Progenitor cells capable of induction into multiple mesenchymal
      lineages have been isolated from human liposuction aspirates. These cells, named
      processed lipoaspirate cells, have previously shown in vitro osteogenic capacity.
      The purpose of this study was to examine the in vivo bone induction capacity of
      bone morphogenetic protein-2 (BMP-2)-transduced processed lipoaspirate cells
      using adipose tissue from multiple harvest sites. METHODS: Processed lipoaspirate
      cells extracted from human abdominal and buttock liposuction aspirates (n = 5)
      and from infrapatellar fat pads (n = 5) were placed in osteogenic media
      containing Dulbecco's Modified Eagle Medium with 10% fetal bovine serum
      supplemented with 50 muM ascorbic acid-2-phosphate and 10 mM beta-glycerol
      phosphate. Half of these cells were transfected with an adenovirus carrying the
      cDNA for bone morphogenetic protein-2 (adBMP-2). These transfected cells were
      then seeded onto collagen I matrices at a concentration of 2 x 10 cells/matrix
      and were placed into the hind limbs of severe combined immunodeficient mice (n =
      10). Nontransfected processed lipoaspirate cells were placed in the contralateral
      limb as a control. After 6 weeks, specimens were analyzed by radiographs,
      densitometry, and hematoxylin and eosin and von Kossa staining. RESULTS: The
      average number of cells extracted from the abdominal/buttock lipoaspirates was
      3.4 x 10 cells/100 ml fat aspirate and 5.5 x 10 cells per infrapatellar fat pad
      (average volume, 20.6 cc). All 10 BMP-2 transfected processed lipoaspirate
      constructs produced abundant radiographic and histologic bone. The bone was
      adequately mineralized and was beginning to establish a marrow cavity. There was
      no quantitative difference in bone production between harvest sites [mean, 2.0 +/
      0.1 aluminum units (knee) versus 2.1 +/- 0.1 aluminum units (abdomen/buttock); p
      = 0.14]. No bone was produced in the negative controls. CONCLUSIONS:
      Multipotential processed lipoaspirate cells can be extracted from adipose tissue
      harvested from liposuction aspirates or from the infrapatellar fat pad of the
      knee. Processed lipoaspirate cells can be transduced with the BMP-2 gene to
      produce abundant in vivo bone. These cells appear to be clinically useful for
      bone tissue engineering applications either as osteoprogenitor cells or as
      delivery vehicles for BMP-2.

PMID- 15861073
TI  - A biomechanical comparison of four extensor tendon repair techniques in zone IV.
AB  - BACKGROUND: This study was designed to evaluate the biomechanical parameters of
      four different suture techniques specifically designed for zone IV extensor
      tendon injuries: the double figure of eight, the double modified Kessler, the six
      strand double-loop, and the modified Becker suturing techniques. Ease of repair,
      tendon shortening, strength to 1-mm gap, strength to 2-mm gap, ultimate strength,
      and mode of repair failure were evaluated. METHODS: Twelve fresh-frozen cadaver
      hand-forearm units (48 fingers) were randomly assigned to the four suture repair
      treatments. The speed of tendon repair as performed by two matched-hand surgeons
      was recorded. Prerepair and postrepair tendon lengths were measured to document
      tendon shortening. The repair was stressed by linear distraction at 2.0 mm/minute
      using a servohydraulic frame. Video recordings of each distraction were
      independently reviewed for biomechanical parameters by three physician-observers
      in a double-blind setup. A one-way analysis of variance and t test analysis was
      performed. RESULTS: Results show that the double figure-of-eight technique and
      the double modified Kessler were significantly (p < 0.05) easier to perform at 7
      minutes 31 seconds and 7 minutes 58 seconds, respectively, than the other two
      techniques. Tendon shortening ranged from 1.9 to 2.4 mm. There was no
      statistically significant difference in tendon shortening among the four
      techniques. Strength to 1-mm gap was significantly higher with the modified
      Becker technique, with a mean 28.8 +/- 8.0 N. This was followed by the six-strand
      double-loop technique, with 21.0 +/- 6.6 N, the double modified Kessler at 17.7
      +/- 4.5 N, and the figure-of-eight technique at 17.5 +/- 2.4 N. Strength to 2-mm
      gap was significantly (p < 0.05) greater for the modified Becker technique and
      the modified Kessler technique at 56.0 +/- 9.2 N and 48.6 +/- 12.6 N,
      respectively, as compared with the other two suture methods. The modified Becker
      technique showed the highest ultimate strength at maximal loading at 63.3 +/- 7.8
      N, followed by the double modified Kessler technique with strength of 56.8 +/-
      14.8 N. Both were significantly stronger than the other two techniques.
      CONCLUSIONS: This study shows that the modified Becker suture technique, although
      not easily performed, proved to be the strongest repair, with a significantly
      greater resistance to 1-mm and 2-mm gap and the greatest ultimate strength on
      maximal loading.

PMID- 15861075
TI  - Frontonasal myocutaneous flap based on the transversus nasalis muscle.

PMID- 15861076
TI  - Use of axial pattern cervico-occipital flaps in restoration of beard defects.

PMID- 15861077
TI  - Functional reconstruction of unilateral, subtotal, full-thickness upper and lower
      eyelid defects with a single hard palate graft covered with advancement
      orbicularis myocutaneous flaps.

PMID- 15861078
TI  - Congenital auricular anomalies: topographic anatomy, embryology, classification,
      and treatment strategies.
AB  - Congenital auricular anomalies are heterogeneous, with various descriptive and
      eponymous terms being used. Current classification systems are useful in guiding
      surgical treatment of severe anomalies. However, they do not generally account
      for the less severe anomalies, which form the majority of congenital auricular
      anomalies, nor their contemporary treatment. In this article, the authors review
      the anatomy and embryology of the external ear and propose a simple
      classification of congenital auricular anomalies that encompasses all forms of
      congenital auricular anomalies, facilitates proper diagnosis, and guides
      treatment. Congenital auricular anomalies should be classified as malformational
      or deformational anomalies. Malformational auricular anomalies are caused by
      embryologic maldevelopment that occurs between the fifth and ninth week of
      gestation resulting in deficient and/or supernumerary auricular components.
      Deformational auricular anomalies result from in utero or ex utero deformational
      forces, including those caused by an aberrant insertion of the intrinsic or
      extrinsic auricular muscles. Malformational auricular anomalies generally require
      surgical correction during childhood or adolescence. For practical purposes,
      deformational auricular anomalies have a full complement of chondrocutaneous
      components that can be digitally manipulated to a normal shape. These anomalies
      are best treated by auricular molding, which is effective if it is initiated
      within the first 3 months of life. Deformational auricular anomalies are best
      regarded as a pediatric public health issue and are best managed nonsurgically.
      Education of neonatal pediatricians, obstetricians, family doctors, and midwives
      will allow proper early diagnosis of all congenital auricular anomalies, which is
      vital to appropriate treatment. These practitioners should be encouraged to
      manage deformational auricular anomalies early in life so that surgery can be
      largely avoided in these patients.

PMID- 15861079
TI  - Pain management after lipoplasty: a study of 303 cases.
AB  - BACKGROUND: The safety and efficiency of liposuction have been proven in several
      studies, but little attention has been paid to postoperative pain. The present
      study was designed to determine the demand for analgesic agents used
      postoperatively after liposuction. METHODS: A total of 303 patients underwent
      ultrasound-assisted liposuction between January 1, 1999, and February 1, 2002, in
      the Department of Plastic Surgery at the Florence Nightingale Hospital, in
      Dusseldorf, Germany. The study is partly retrospective of the postoperative
      demand for analgesic agents. RESULTS: The study group of 244 female and 59 male
      patients was 42.2 +/- 13.6 years of age (range, 12 to 78 years). The average
      total suction volume removed was 2404.6 +/- 1704.2 cc (range, 90 to 9100 cc). Of
      303 patients, 146 (48.2 percent) did not require any additional analgesic agents
      on the day of the operation, with 157 (51.8 percent) asking for pain relief on
      the operation day. On the first postoperative day, 88 (29.0 percent) of all
      liposuction patients asked for pain medication. That number of patients decreased
      to 28 (9.2 percent) on postoperative day 2, 21 (6.9 percent) on postoperative day
      3, 11 (3.6 percent) on postoperative day 4, five (1.7 percent) on postoperative
      day 5, four (1.3 percent) on postoperative day 6, and zero on postoperative day
      7. The data were further specified concerning details on analgesic agents. Of 303
      patients, 146 (48.2 percent) did not require any form of pain medication. For 61
      patients (20.1 percent), light analgesic agents were sufficient. Eighty-three
      patients (27.4 percent) asked for stronger medication, such as tramadol. Only 13
      patients (4.3 percent) needed strong opioids for adequate pain management. No
      statistically significant difference concerning postoperative pain was observed
      between patients who were operated on under local anesthesia and those who
      received general anesthesia. CONCLUSIONS: This study gives clear proof that
      liposuction is a relatively painless procedure, and 48.2 percent off all
      liposuction patients do not need any pain medication at all. If they do need
      analgesic agents postoperatively, in most cases, analgesic therapy is sufficient
      with oral pain medication such as paracetamol or tramadol. In addition, patients
      can be reassured that merely 1 week after the operation very few patients
      complain of pain, and they can return to normal life without any complications
      concerning pain.

PMID- 15861081
TI  - Current trends in local anesthesia in cosmetic plastic surgery of the head and
      neck: results of a German national survey and observations on the use of
      ropivacaine.
AB  - BACKGROUND: The goal of this study was to evaluate at the national level the
      current practice in the use of local anesthetics in cosmetic head and neck
      surgery and to compare the results with the novel local anesthesia technique used
      in the authors' department over the past 2 years. METHODS: A questionnaire was
      posted to all 211 board-certified members of the Association of German Plastic
      Surgeons. The questions related to the daily practice in rhinoplasty,
      blepharoplasty, otoplasty, face lift, and forehead lift. The focus was laid on
      anesthesia techniques, local anesthetics, vasoconstricting agents, dosages,
      activity onset, observed side effects, mean duration of each procedure type, and
      surgeon satisfaction with the anesthetic used. RESULTS: A total of 86
      questionnaires (40.8 percent) were returned. The overall analysis revealed that
      local anesthetics were used in 88.9 percent of all cosmetic procedures of the
      head and neck. Prilocaine 1% (Xylonest; AstraZeneca, Wedel, Germany) was the most
      frequently used local anesthetic (32.0 percent), followed by lidocaine 1%
      (Xylocaine; AstraZeneca) and mepivacaine 1% (Scandicaine; AstraZeneca).
      Ropivacaine 0.2% (Naropin; AstraZeneca) was used only by 1.1 percent and
      ropivacaine 0.75% only by 0.9 percent (including two of the authors).
      Approximately half of the respondents (47.2 percent) used epinephrine 1:100,000
      for vasoconstriction. In face lifts, the necessity of repeated "top-up"
      infiltration was reported in more than half (54.7 percent) of the procedures. Ten
      percent of surgeons surpassed the maximum recommended dosages when working
      without ropivacaine. Overall adverse cardiovascular effects were reported in 5.9
      percent of rhinoplasties and 8.1 percent of face lifts performed mostly with
      prilocaine and lidocaine. No adverse cardiovascular reactions or overdoses were
      noticed with the use of ropivacaine. CONCLUSIONS: The survey showed a clear trend
      toward the increasing use of local anesthetics in cosmetic surgery of the head
      and neck. Although the use of prilocaine and lidocaine prevailed, adverse
      cardiovascular reactions in up to 8.1 percent seem high for cosmetic procedures.
      Furthermore, the need of additional intraoperative top-up infiltration adds to an
      uncontrolled cumulative effect and patient discomfort. On the basis of their
      positive 2 years of experience with ropivacaine, the authors strongly believe
      that ropivacaine offers significant advantages, both in efficacy and prolonged
      duration of analgesia, while reducing the risk for adverse side effects due to
      lesser toxicity. This observation deserves further investigation in an
      established comparative study.

PMID- 15861082
TI  - Long-term results of upper lips treated for rhytides with carbon dioxide laser.
AB  - BACKGROUND: Carbon dioxide laser resurfacing has been widely reported as an
      effective method for smoothing facial rhytides. However, limited series have been
      published describing the long-term results. This retrospective study was
      undertaken to assess the long-term aesthetic results of upper lips treated for
      rhytides with the SilkTouch carbon dioxide laser (Sharplan Lasers, Inc., Warwick,
      R.I.). METHODS: The results of 35 patients were reviewed and evaluated, including
      patient demographics, skin type, laser pass data, laser parameters, and long-term
      aesthetic results and complications. Aesthetic results were graded by independent
      reviewers using a standardized photographic rhytide scale, and all patient
      satisfaction rates were evaluated by means of a five-point visual analogue scale.
      RESULTS: Rhytides were almost completely ablated at 3-month follow-up. A
      persistence of approximately 81 percent of the rhytide reduction was shown at a
      follow-up period of 2.1 to 6.3 years (average, 4.5 years). Most of the patients
      would undergo the procedure again and would recommend it to their friends. The
      only drawback and main long-term complication was the high rate of
      hypopigmentation (57.1 percent). CONCLUSIONS: This study clearly demonstrates
      that laser resurfacing with the SilkTouch carbon dioxide laser is a highly
      effective treatment of rhytides of the upper lip that will last for a long time,
      but there is a high rate of hypopigmentation.

PMID- 15861083
TI  - Long-term follow-up of correction of rectus diastasis.
AB  - BACKGROUND: Correction of rectus diastasis is a procedure performed by most
      surgeons during abdominoplasty. The purpose of this study was to demonstrate the
      long-term efficacy of the correction of rectus diastasis when plication of the
      anterior rectus sheath is performed with a nonabsorbable suture. METHODS: Twelve
      female patients who underwent abdominoplasty were studied. Rectus diastasis was
      measured preoperatively with two computed tomographic scan slices: one above and
      one below the umbilicus. The bony levels where the slices were obtained served as
      a reference for the postoperative computed tomographic scans. During the
      operation, rectus diastasis was measured at the same levels as the preoperative
      scan slices. At the same time, the necessary force to bring the medial edge of
      the rectus muscle to the midline was measured with a dynamometer. Postoperative
      scans were obtained at 3 weeks and 6 months after the operation. A long-term
      follow-up scan was obtained from 76 to 84 months postoperatively for every
      patient. RESULTS: The 3-week postoperative scan proved that the correction of
      rectus diastasis had been achieved by the procedure. Despite the fact that there
      were different levels of abdominal wall resistance and that the average weight
      gain in this period was 6.5 kg, the long-term computed tomographic scans showed
      that there was no recurrence of rectus diastasis in any patient of this series,
      both in the superior and inferior abdomen. CONCLUSIONS: Plication of the anterior
      rectus sheath with nonabsorbable suture appears to be a long-lasting procedure
      for correcting rectus diastasis.

PMID- 15861085
TI  - Rapid absorption of tumescent lidocaine above the clavicles: a prospective
      clinical study.
AB  - BACKGROUND: Tumescent local anesthesia has been adapted for surgery of the face
      and neck, but there are no data regarding drug absorption when tumescent
      injection is used in this region. The aim of this study was to characterize the
      changes in plasma lidocaine concentrations over time when a tumescent solution is
      injected into the subcutaneous tissue of the neck. The study was carried out in
      human volunteer subjects, and injection of lidocaine to the thighs provided
      control data. METHODS: Eight healthy female volunteer subjects were studied twice
      using a prospective, crossover design. Tumescent lidocaine solution was injected
      into the subcutaneous tissue of the neck in one session and the thighs in another
      session. The order of injection was randomized. Blood samples were collected for
      14 hours after injection, and the plasma concentration of lidocaine measured. The
      injected solution consisted of lidocaine 0.1%, NaHCO3 12.5 mEq/L, and epinephrine
      1:1,000,000 in normal saline. A standardized dose of lidocaine (7 mg/kg) was used
      for each injection and no surgical procedure was performed. RESULTS: All subjects
      completed the study. Subject weight was 66.1 +/- 12.8 kg, body fat was 29.0 +/-
      4.7 percent, and body mass index was 23.8 +/- 3.1 kg/m2. The average time to
      reach peak lidocaine concentration after neck injection was 5.8 hours, whereas
      peak lidocaine concentration after thigh injection did not occur until 12.0
      hours. This difference of 6.2 hours was highly significant (p = 0.009). The
      average peak concentration after neck injection was 16 percent greater than that
      after thigh injection (0.94 microg/ml versus 0.81 microg/ml), with the difference
      approaching significance (p = 0.06). No adverse reactions were noted.
      CONCLUSIONS: Tumescent injection above the clavicles results in a rapid rise in
      plasma lidocaine concentration when compared with injection to the lower
      extremities. Toxic symptoms could occur much earlier than expected for lower
      extremity tumescent anesthesia. In addition, dangerous plasma levels could occur
      if tumescent anesthesia in the lower extremities is followed by tumescent
      injection above the clavicles, because the absorption curves would be
      superimposed.

PMID- 15861086
TI  - The lesser and third occipital nerves and migraine headaches.
AB  - BACKGROUND: Reports of a correlation between relief of migraine headaches and
      resection of corrugator muscles or injection of botulinum A toxin have renewed
      interest in finding the cause of migraine headaches and identifying the trigger
      sites. Four trigger sites have been described. One of these is along the course
      of the greater occipital nerve. Recent anatomical studies of this nerve have
      defined its location with respect to external landmarks, leading to new studies
      with gratifying results. There is a subset of patients who undergo
      chemodenervation or surgical release of the greater occipital nerve and note
      improvement or elimination of the symptoms along the greater occipital nerve
      course but who experience an emergence of migraine headache symptoms laterally.
      The authors propose the lesser occipital nerve as the source of pain in those who
      experience headaches laterally and involvement of the third occipital nerve in
      those who notice residual symptoms in the midportion of the occipital region.
      METHODS: To test this hypothesis anatomically, 20 cadaver heads were dissected to
      trace the course of the lesser occipital nerve and third occipital nerve and
      define the location of these nerves with respect to external landmarks. The
      midline and a line drawn between the inferiormost points of the external auditory
      canals were used to obtain standardized measurements of these nerves. RESULTS:
      The location of emergence of the lesser occipital nerve was determined to be an
      area centered 65.4 +/- 11.6 mm from midline and 53.3 +/- 15.6 mm below the line
      between the external auditory canals. The third occipital nerve was found 13.2 +/
      5.3 mm from midline and 62.0 +/- 20.0 mm down from the line between the two
      external auditory canals. CONCLUSIONS: This information can be used to conduct
      clinical trials of chemodenervation of these nerves in an attempt to eliminate
      migraine symptoms in the subset of patients who continue to experience residual
      symptoms after surgical release of the greater occipital nerve.

PMID- 15861088
TI  - The "anterior-only" approach to neck rejuvenation: an alternative to face lift
      surgery.
AB  - BACKGROUND: The ideal procedure for those patients with aging of the lower face
      and neck is a cervicofacial rhytidectomy. However, within this group is a subset
      of patients whose goals can be met with a lesser procedure. These patients must
      be interested in profile change only, with no desired change in the midface.
      METHODS: Patients undergoing neck rejuvenation by means of a submental approach
      fall into three groups: (1) patients with obtuse cervicomental angles and good
      skin elasticity (who may be treated with liposuction alone); (2) patients with
      subplatysmal fat or mild to moderate skin and muscle laxity (these patients are
      best treated by anterior lipectomy and platysmaplasty); and (3) patients with
      marked skin excess or severe skin laxity (best treated by procedures with excised
      skin, i.e., traditional face lift or direct excision of neck skin and Z-plasty).
      RESULTS: Thirty-three consecutive patients with mild (grade II, 16 patients),
      moderate (grade III, 11 patients), and severe (grade IV, six patients)
      cervicomental angle deformities were treated with anterior platysmaplasty and
      submental lipectomy. Twenty of 33 patients improved by one grade (61 percent),
      whereas 12 of 33 improved by two grades (36 percent). CONCLUSIONS: Young patients
      with minimal subplatysmal fat can be treated by liposuction alone. Patients with
      subplatysmal fat and mild or moderate skin or muscle laxity will obtain
      consistent results with platysmaplasty and submental lipectomy. Skin excisional
      procedures are reserved for those patients with severe skin excess or laxity.

PMID- 15861089
TI  - Analysis of facial skin thickness: defining the relative thickness index.
AB  - BACKGROUND: The determination of human skin thickness has been achieved through
      various methods, both in vivo and in vitro. Ultrasound and histometric analyses
      have been the most commonly used. However, absolute values of epidermal and
      dermal thicknesses have demonstrated variability among the different modalities,
      leaving questions regarding the ability to standardize or compare results of
      different studies. METHODS: A cadaver study was designed to examine skin
      thicknesses in multiple anatomical sites from the same subject. Using three fresh
      adult cadavers, skin biopsy specimens were obtained at 15 facial sites that were
      identified as clinically relevant locations: upper lip vermilion, lower lip
      vermilion, philtral column, chin, upper eyelid, lower eyelid, brow/forehead,
      submental crease, right cheek, left cheek, right neck, left neck, malar eminence,
      nasal dorsum, and nasal tip. Histometric measurements were obtained at each
      location. RESULTS: In all subjects, the upper eyelid had the thinnest skin and
      was used as the denominator to calculate relative ratios of skin thicknesses with
      respect to other sites of the face. Using the upper eyelid average skin
      thickness, the nasal tip skin thickness was 3.30 times thicker and the
      brow/forehead was 2.8 times thicker. CONCLUSIONS: The authors propose a
      standardized and clinically useful method of skin thickness analysis by defining
      the relative thickness index. By examining relative values of skin thickness,
      using each subject as his or her own control, the authors demonstrated consistent
      ratios of dermal and epidermal thickness from one facial site to another.

PMID- 15861095
TI  - Maximizing the use of the abdominoplasty incision in terms of reconstructive
      surgery, as well.

PMID- 15861096
TI  - Safety of ketamine/diazepam anesthesia.

PMID- 15861098
TI  - Prospective analysis of the outcome of subpectoral augmentation.

PMID- 15861100
TI  - Nasal osteotomies: a clinical comparison of the perforating methods versus the
      continuous technique.

PMID- 15861101
TI  - Diagnosis of pilomatrixoma in childhood.

PMID- 15861102
TI  - Treatment of the lower third of the nose and dynamic nasal tip ptosis with Botox.

PMID- 15861103
TI  - The nasal alar elevator: an effective tool in the presurgical treatment of
      infants born with cleft lip.

PMID- 15861104
TI  - How to find a foreign body: wire grid technique.

PMID- 15861105
TI  - A technique to correct severe ectropion.

PMID- 15861106
TI  - Bio-alkamid: avoiding the leak.

PMID- 15861107
TI  - Subcutaneous fat necrosis of the newborn.

PMID- 15861108
TI  - Vaginal labioplasty.

PMID- 15861109
TI  - A simple instrumentation during tissue expander placement.

PMID- 15861110
TI  - Transplantation of the vascularized bone allograft into the inguinal region.

PMID- 15861111
TI  - The ballooning maneuver in breast augmentation.

PMID- 15861112
TI  - Use of a needle guard in syringe nipple splinting.

PMID- 15861113
TI  - Axillary reconstruction with a musculoglandulocutaneous island flap.

PMID- 15861114
TI  - Deepithelialization of breasts with scissors.

PMID- 15861115
TI  - Flexor sheath catheterization.

PMID- 15861116
TI  - Management of epinephrine injection injury to the digit.

PMID- 15861117
TI  - A novel use of the free gracilis muscle flap in hand trauma.

PMID- 15861118
TI  - Easy perioperative photography by digital camera covered with a sterile nylon
      bag.

PMID- 15861119
TI  - Different opinion on Botox.

PMID- 15861120
TI  - A technique to localize the radio-opaque foreign body.

PMID- 15861121
TI  - "Flag" drain fixation: a secure method.

PMID- 15861122
TI  - Perfectionism and interest in cosmetic surgery.

PMID- 15861123
TI  - Where plastic surgery has gone the past few years.

PMID- 15861125
TI  - A "gain of function" mutation in a protein mediates production of novel modified
      nucleosides.
AB  - The mutation sufY204 mediates suppression of a +1 frameshift mutation in the
      histidine operon of Salmonella enterica serovar Typhimurium and synthesis of two
      novel modified nucleosides in tRNA. The sufY204 mutation, which results in an
      amino-acid substitution in a protein, is, surprisingly, dominant over its wild
      type allele and thus it is a "gain of function" mutation. One of the new
      nucleosides is 5-methylaminomethyl-2-thiouridine (mnm(5)s(2)U34) modified by
      addition of a C(10)H(17) side chain of unknown structure. Increased amounts of
      both nucleosides in tRNA are correlated to gene dosage of the sufY204 allele, to
      an increased efficiency of frameshift suppression, and to a decreased amount of
      the wobble nucleoside mnm(5)s(2)U34 in tRNA. Purified tRNA(Gln)(cmnm(5)s(2)UUG)
      in the mutant strain contains a modified nucleoside similar to the novel
      nucleosides and the level of aminoacylation of tRNA(Gln)(cmnm(5)s(2)UUG) was
      reduced to 26% compared to that found in the wild type (86%). The results are
      discussed in relation to the mechanism of reading frame maintenance and the
      evolution of modified nucleosides in tRNA.

PMID- 15861126
TI  - Crystal structure of pyruvate dehydrogenase kinase 3 bound to lipoyl domain 2 of
      human pyruvate dehydrogenase complex.
AB  - The human pyruvate dehydrogenase complex (PDC) is regulated by reversible
      phosphorylation by four isoforms of pyruvate dehydrogenase kinase (PDK). PDKs
      phosphorylate serine residues in the dehydrogenase (E1p) component of PDC, but
      their amino-acid sequences are unrelated to eukaryotic Ser/Thr/Tyr protein
      kinases. PDK3 binds to the inner lipoyl domains (L2) from the 60-meric
      transacetylase (E2p) core of PDC, with concomitant stimulated kinase activity.
      Here, we present crystal structures of the PDK3-L2 complex with and without bound
      ADP or ATP. These structures disclose that the C-terminal tail from one subunit
      of PDK3 dimer constitutes an integral part of the lipoyl-binding pocket in the N
      terminal domain of the opposing subunit. The two swapped C-terminal tails promote
      conformational changes in active-site clefts of both PDK3 subunits, resulting in
      largely disordered ATP lids in the ADP-bound form. Our structural and biochemical
      data suggest that L2 binding stimulates PDK3 activity by disrupting the ATP lid,
      which otherwise traps ADP, to remove product inhibition exerted by this
      nucleotide. We hypothesize that this allosteric mechanism accounts, in part, for
      E2p-augmented PDK3 activity.

PMID- 15861127
TI  - A Kaposi's sarcoma virus RNA element that increases the nuclear abundance of
      intronless transcripts.
AB  - The Kaposi's sarcoma-associated herpesvirus produces a 1077 nucleotide noncoding,
      polyadenylated, exclusively nuclear RNA called PAN that is highly expressed in
      lytically infected cells. We report that PAN contains a novel post
      transcriptional element essential for its abundant accumulation. The element, PAN
      ENE (PAN RNA expression and nuclear retention element), increases the efficiency
      of 3'-end formation in vivo and is sufficient to enhance RNA abundance from an
      otherwise inefficiently expressed intronless beta-globin construct. The PAN-ENE
      does not concomitantly increase the production of encoded protein. Rather, it
      retains the unspliced beta-globin mRNA in the nucleus. Tethering of export
      factors can override the nuclear retention of the PAN-ENE, supporting a mechanism
      whereby the PAN-ENE blocks assembly of an export-competent mRNP. The activities
      of the PAN-ENE are specific to intronless constructs, since inserting the PAN-ENE
      into a spliced beta-globin construct has no effect on mRNA abundance and does not
      affect localization. This is the first characterization of a cis-acting element
      that increases RNA abundance of intronless transcripts but inhibits assembly of
      an export-competent mRNP.

PMID- 15861128
TI  - Antiapoptotic function of RNA-binding protein HuR effected through prothymosin
      alpha.
AB  - We report the antiapoptotic effect of RNA-binding protein HuR, a critical
      regulator of the post-transcriptional fate of target transcripts. Among the most
      prominent mRNAs complexing with HuR is that encoding prothymosin alpha
      (ProTalpha), an inhibitor of the apoptosome. In HeLa cells, treatment with the
      apoptotic stimulus ultraviolet light (UVC) triggered the mobilization of
      ProTalpha mRNA to the cytoplasm and onto heavier polysomes, where its association
      with HuR increased dramatically. Analysis of a chimeric ProTalpha mRNA directly
      implicated HuR in regulating ProTalpha production: ProTalpha translation and
      cytoplasmic concentration increased in HuR-overexpressing cells and declined in
      cells in which HuR levels were lowered by RNA interference. Importantly, the
      antiapoptotic influence engendered by HuR was vitally dependent on ProTalpha
      expression, since use of oligomers that blocked ProTalpha translation abrogated
      the protective effect of HuR. Together, our data support a regulatory scheme
      whereby HuR binds the ProTalpha mRNA, elevates its cytoplasmic abundance and
      translation, and thereby elicits an antiapoptotic program.

PMID- 15861129
TI  - Myeloid leukemia factor 1 regulates p53 by suppressing COP1 via COP9 signalosome
      subunit 3.
AB  - Myeloid leukemia factor 1 (MLF1) was first identified as the leukemic fusion
      protein NPM-MLF1 generated by the t(3;5)(q25.1;q34) chromosomal translocation.
      Although MLF1 expresses normally in a variety of tissues including hematopoietic
      stem cells and the overexpression of MLF1 correlates with malignant
      transformation in human cancer, little is known about how MLF1 is involved in the
      regulation of cell growth. Here we show that MLF1 is a negative regulator of cell
      cycle progression functioning upstream of the tumor suppressor p53. MLF1 induces
      p53-dependent cell cycle arrest in murine embryonic fibroblasts. This action
      requires a novel binding partner, subunit 3 of the COP9 signalosome (CSN3). A
      reduction in the level of CSN3 protein with small interfering RNA abrogated MLF1
      induced G1 arrest and impaired the activation of p53 by genotoxic stress.
      Furthermore, ectopic MLF1 expression and CSN3 knockdown inversely affect the
      endogenous level of COP1, a ubiquitin ligase for p53. Exogenous expression of
      COP1 overcomes MLF1-induced growth arrest. These results indicate that MLF1 is a
      critical regulator of p53 and suggest its involvement in leukemogenesis through a
      novel CSN3-COP1 pathway.

PMID- 15861130
TI  - PIP2 signaling in lipid domains: a critical re-evaluation.
AB  - Microdomains such as rafts are considered as scaffolds for phosphatidylinositol
      (4,5) bisphosphate (PIP2) signaling, enabling PIP2 to selectively regulate
      different processes in the cell. Enrichment of PIP2 in microdomains was based on
      cholesterol-depletion and detergent-extraction studies. Here we show that two
      distinct phospholipase C-coupled receptors (those for neurokinin A and
      endothelin) share the same, homogeneously distributed PIP2 pool at the plasma
      membrane, even though the neurokinin A receptor is localized to microdomains and
      is cholesterol dependent in its PIP2 signaling whereas the endothelin receptor is
      not. Our experiments further indicate that detergent treatment causes PIP2
      clustering and that cholesterol depletion interferes with basal, ligand
      independent recycling of the neurokinin A receptor, thereby providing alternative
      explanations for the enrichment of PIP2 in detergent-insoluble membrane fractions
      and for the cholesterol dependency of PIP2 breakdown, respectively.

PMID- 15861131
TI  - A quasi-atomic model of human adenovirus type 5 capsid.
AB  - Adenoviruses infect a wide range of vertebrates including humans. Their
      icosahedral capsids are composed of three major proteins: the trimeric hexon
      forms the facets and the penton, a noncovalent complex of the pentameric penton
      base and trimeric fibre proteins, is located at the 12 capsid vertices. Several
      proteins (IIIa, VI, VIII and IX) stabilise the capsid. We have obtained a 10 A
      resolution map of the human adenovirus 5 by image analysis from cryo-electron
      micrographs (cryoEMs). This map, in combination with the X-ray structures of the
      penton base and hexon, was used to build a quasi-atomic model of the arrangement
      of the two major capsid components and to analyse the hexon-hexon and hexon
      penton interactions. The secondary proteins, notably VIII, were located by
      comparing cryoEM maps of native and pIX deletion mutant virions. Minor proteins
      IX and IIIa are located on the outside of the capsid, whereas protein VIII is
      organised with a T=2 lattice on the inner face of the capsid. The capsid
      organisation is compared with the known X-ray structure of bacteriophage PRD1.

PMID- 15861132
TI  - Interplay between the retinoblastoma protein and LEK1 specifies stem cells toward
      the cardiac lineage.
AB  - The molecular mechanisms governing early cardiogenesis are still largely unknown.
      Interestingly, the retinoblastoma protein (Rb), a regulator of cell cycle, has
      recently emerged as a new candidate regulating cell differentiation. Rb-/- mice
      die at midgestation and mice lacking E2f1/E2f3, downstream components of the Rb
      dependent transcriptional pathway, die of heart failure. To gain insight into the
      function of Rb pathway in early cardiogenesis, we used Rb-/- embryonic stem (ES)
      cells differentiating into cardiomyocytes. Rb-/- cells displayed a dramatic delay
      in expression of cardiac-specific transcription factors and in turn in the whole
      process of cardiac differentiation. The phenotype of Rb-/- ES cell-derived
      cardiomyocytes was rescued by reintroducing Rb in cardiac progenitors, by
      stimulating the BMP-dependent cardiogenic pathway or by overexpression of Nkx2.5.
      ES cells deficient in the recently identified factor LEK1, a murine homolog of
      the cardiomyogenic factor 1, or specific disruption of Rb-LEK1 interaction into
      the nucleus of differentiating ES cells recapitulated the delay in cardiac
      differentiation of Rb-/- ES cells. Thus, we provide evidence for a novel Rb/LEK1
      dependent and BMP-independent transcriptional program, which plays a pivotal role
      in priming ES cells toward a cardiac fate.

PMID- 15861133
TI  - HPV31 E7 facilitates replication by activating E2F2 transcription through its
      interaction with HDACs.
AB  - The E7 proteins of human papillomaviruses (HPVs) contribute to oncogenesis by
      associating with Rb family members as well class I histone deacetylases (HDACs).
      The binding of HDACs is also important for the maintenance of viral episomes
      during the differentiation-dependent productive life cycle. The effects of E7 and
      other viral proteins on E2F family members were examined in differentiating
      keratinocytes. E7 was found to specifically activate E2F2 transcription in
      suprabasal keratinocytes through its ability to bind HDACs. Chromatin
      immunoprecipitation assays demonstrated that, in differentiating cells, E7 acts
      to inhibit HDAC binding to the E2F2 promoter resulting in activation of
      expression. Reduction of E2F2 levels through the use of siRNA confirmed that E2F2
      expression facilitated HPV replication but its loss did not affect cell
      proliferation. Our study demonstrates a mechanism by which binding of HDACs to E7
      directly modulates viral replication and identifies E2F2 as a possible target for
      antiviral therapies.

PMID- 15861134
TI  - Tissue plasminogen activator mediates amyloid-induced neurotoxicity via Erk1/2
      activation.
AB  - Tissue plasminogen activator (tPA) is the main activator of plasminogen into
      plasmin in the brain where it may have beneficial roles but also neurotoxic
      effects that could be plasmin dependent or not. Little is known about the
      substrates and pathways that mediate plasmin-independent tPA neurotoxicity. Here
      we show in primary hippocampal neurons that tPA promotes a catalytic-independent
      activation of the extracellular regulated kinase (Erk)1/2 signal transduction
      pathway through the N-methyl-D-aspartate receptor, G-proteins and protein kinase
      C. This results in GSK3 activation in a process that requires de novo synthesis
      of proteins, and leads to tau aberrant phosphorylation, microtubule
      destabilization and apoptosis. Similar effects are produced by amyloid aggregates
      in a tPA-dependent manner, as demonstrated by pharmacological treatments and in
      wt and tPA-/- mice neurons. Consistently, in Alzheimer's disease (AD) patients'
      brains, high levels of tPA colocalize with amyloid-rich areas, activated Erk1/2
      and phosphorylated tau. This is the first demonstration of an intracellular
      pathway by which tPA triggers kinase activation, tau phosphorylation and
      neurotoxicity, suggesting a key role for this molecule in AD pathology.

PMID- 15861135
TI  - TNF-alpha induced c-IAP1/TRAF2 complex translocation to a Ubc6-containing
      compartment and TRAF2 ubiquitination.
AB  - Signaling through tumor necrosis factor receptor 2 (TNF-R2) results in
      ubiquitination of TRAF2 by the E3 c-IAP1. In this report, we confirm that TRAF2
      translocates to a Triton X-100 (TX)-insoluble compartment upon TNF-R2 engagement.
      Moreover, TRAF2 ubiquitination occurs in this compartment, from which TRAF2 is
      degraded in a proteasome-dependent manner. Confocal microscopy demonstrated that
      the TX-insoluble compartment is perinuclear and co-localizes with endoplasmic
      reticulum (ER) markers. The ER transmembrane Ubc6 bound to c-IAP1 and served as a
      cognate E2 for c-IAP1's E3 activity in vitro. Furthermore, Ubc6 co-localized with
      translocated TRAF2/c-IAP1 in the ER-associated compartment in vivo, and a
      catalytically inactive Ubc6 mutant inhibited TNF-alpha-induced, TNF-R2-dependent
      TRAF2 degradation. These results indicate that upon TNF-R2 signaling,
      translocation of TRAF2 and c-IAP1 to an ER-associated, Ubc6-containing
      perinuclear compartment is required for the ubiquitination of TRAF2 by c-IAP1.
      Therefore, the ER plays a key role in the TNF-R-mediated signal transduction
      cascade by acting as a site of assembly for E2/E3/substrate complexes.

PMID- 15861136
TI  - The tRNA methylase METTL1 is phosphorylated and inactivated by PKB and RSK in
      vitro and in cells.
AB  - A substrate for protein kinase B (PKB)alpha in HeLa cell extracts was identified
      as methyltransferase-like protein-1 (METTL1), the orthologue of trm8, which
      catalyses the 7-methylguanosine modification of tRNA in Saccharomyces cerevisiae.
      PKB and ribosomal S6 kinase (RSK) both phosphorylated METTL1 at Ser27 in vitro.
      Ser27 became phosphorylated when HEK293 cells were stimulated with insulin-like
      growth factor-1 (IGF-1) and this was prevented by inhibition of
      phosphatidyinositol 3-kinase. The IGF-1-induced Ser27 phosphorylation did not
      occur in 3-phosphoinositide-dependent protein kinase-1 (PDK1)-deficient embryonic
      stem cells, but occurred normally in PDK1[L155E] cells, indicating that the
      effect of IGF-1 is mediated by PKB. METTL1 also became phosphorylated at Ser27 in
      response to phorbol-12-myristate 13-acetate and this was prevented by PD 184352
      or pharmacological inhibition of RSK. Phosphorylation of METTL1 by PKB or RSK
      inactivated METTL1 in vitro, as did mutation of Ser27 to Asp or Glu. Expression
      of METTL1[S27D] or METTL1[S27E] did not rescue the growth phenotype of yeast
      lacking trm8. In contrast, expression of METTL1 or METTL1[S27A] partially rescued
      growth. These results demonstrate that METTL1 is inactivated by PKB and RSK in
      cells, and the potential implications of this finding are discussed.

PMID- 15861137
TI  - Association of Csk to VE-cadherin and inhibition of cell proliferation.
AB  - Vascular endothelial cadherin (VE-cadherin) mediates contact inhibition of cell
      growth in quiescent endothelial cell layers. Searching for proteins that could be
      involved in VE-cadherin signaling, we found the cytosolic C-terminal Src kinase
      (Csk), a negative regulator of Src family kinases. We show that Csk binds via its
      SH2 domain to the phosphorylated tyrosine 685 of VE-cadherin. VE-cadherin
      recruits Csk to cell contacts and both proteins can be co-precipitated from cell
      lysates of transfected cells and endothelial cells. Association of VE-cadherin
      and Csk in endothelial cells increased with increasing cell density. CHO cells
      expressing the tyrosine replacement mutant VE-cadherin-Y685F grow to higher cell
      densities than cells expressing wild-type VE-cadherin. Overexpression of Csk in
      these cells under an inducible promoter inhibits cell proliferation in the
      presence and absence of VE-cadherin, but not in the presence of VE-cadherin
      Y685F. Reduction of Csk expression by RNA interference enhances endothelial cell
      proliferation. Our results suggest that the phosphorylated tyrosine residue 685
      of VE-cadherin and probably the binding of Csk to this site are involved in
      inhibition of cell growth triggered by cell density.

PMID- 15861138
TI  - Mot1-mediated control of transcription complex assembly and activity.
AB  - Mot1 is an essential Snf2/Swi2-related ATPase and TATA-binding protein (TBP)
      associated factor (TAF). In vitro, Mot1 utilizes ATP hydrolysis to disrupt TBP
      DNA complexes, but the relationship of this activity to Mot1's in vivo function
      is unclear. Chromatin immunoprecipitation was used to determine how Mot1 affects
      the assembly of preinitiation complexes (PICs) at Mot1-controlled promoters in
      vivo. We find that the Mot1-repressed HSP26 and INO1 promoters are both regulated
      by TBP recruitment; inactivation of Mot1 leads to increased PIC formation
      coincident with derepression of transcription. For the Mot1-activated genes BNA1
      and URA1, inactivation of Mot1 also leads, remarkably, to increased TBP binding
      to the promoters, despite the fact that transcription of these genes is
      obliterated in mot1 cells. In contrast, levels of Taf1, TFIIB, and RNA polymerase
      II are reduced at Mot1-activated promoters in mot1 cells. These results suggest
      that Mot1-mediated displacement of TBP underlies its mechanism of repression and
      activation at these genes. We suggest that at activated promoters, Mot1
      disassembles transcriptionally inactive TBP, thereby facilitating the formation
      of a TBP complex that supports functional PIC assembly.

PMID- 15861139
TI  - Minor folding defects trigger local modification of glycoproteins by the ER
      folding sensor GT.
AB  - UDP-glucose:glycoprotein glucosyltransferase (GT) is a key component of the
      glycoprotein-specific folding and quality control system in the endoplasmic
      reticulum. By exclusively reglucosylating incompletely folded and assembled
      glycoproteins, it serves as a folding sensor that prolongs the association of
      newly synthesized glycoproteins with the chaperone-like lectins calnexin and
      calreticulin. Here, we address the mechanism by which GT recognizes and labels
      its substrates. Using an improved inhibitor assay based on soluble conformers of
      pancreatic ribonuclease in its glycosylated (RNase B) and unglycosylated (RNase
      A) forms, we found that the protein moiety of a misfolded conformer alone is
      sufficient for specific recognition by GT in vitro. To investigate the
      relationship between recognition and glucosylation, we tested a variety of
      glycosylation mutants of RNase S-Protein and an RNase mutant with a local folding
      defect [RNase C65S, C72S], as well as a series of loop insertion mutants. The
      results indicated that local folding defects in an otherwise correctly folded
      domain could be recognized by GT. Only glycans attached to the polypeptide within
      the misfolded sites were glucosylated.

PMID- 15861140
TI  - A novel mechanism of nuclear envelope break-down in a fungus: nuclear migration
      strips off the envelope.
AB  - In animals, the nuclear envelope disassembles in mitosis, while budding and
      fission yeast form an intranuclear spindle. Ultrastructural data indicate that
      basidiomycetes, such as the pathogen Ustilago maydis, undergo an 'open mitosis'.
      Here we describe the mechanism of nuclear envelope break-down in U. maydis. In
      interphase, the nucleus resides in the mother cell and the spindle pole body is
      inactive. Prior to mitosis, it becomes activated and nucleates microtubules that
      reach into the daughter cell. Dynein appears at microtubule tips and exerts force
      on the spindle pole body, which leads to the formation of a long nuclear
      extension that reaches into the bud. Chromosomes migrate through this extension
      and together with the spindle pole bodies leave the old envelope, which remains
      in the mother cell until late telophase. Inhibition of nuclear migration or
      deletion of a Tem1p-like GTPase leads to a 'closed' mitosis, indicating that
      spindle pole bodies have to reach into the bud where MEN signalling participates
      in envelope removal. Our data indicate that dynein-mediated premitotic nuclear
      migration is essential for envelope removal in U. maydis.

PMID- 15861147
TI  - Working with imported GEMs: a cautionary tale.

PMID- 15861141
TI  - Crystal structure of the human urokinase plasminogen activator receptor bound to
      an antagonist peptide.
AB  - We report the crystal structure of a soluble form of human urokinase-type
      plasminogen activator receptor (uPAR/CD87), which is expressed at the invasive
      areas of the tumor-stromal microenvironment in many human cancers. The structure
      was solved at 2.7 A in association with a competitive peptide inhibitor of the
      urokinase-type plasminogen activator (uPA)-uPAR interaction. uPAR is composed of
      three consecutive three-finger domains organized in an almost circular manner,
      which generates both a deep internal cavity where the peptide binds in a helical
      conformation, and a large external surface. This knowledge combined with the
      discovery of a convergent binding motif shared by the antagonist peptide and uPA
      allowed us to build a model of the human uPA-uPAR complex. This model reveals
      that the receptor-binding module of uPA engages the uPAR central cavity, thus
      leaving the external receptor surface accessible for other protein interactions
      (vitronectin and integrins). By this unique structural assembly, uPAR can
      orchestrate the fine interplay with the partners that are required to guide uPA
      focalized proteolysis on the cell surface and control cell adhesion and
      migration.

PMID- 15861150
TI  - When the IACUC and AV don't agree, who wins?: Veterinary variability.

PMID- 15861151
TI  - When the IACUC and AV don't agree, who wins?

PMID- 15861152
TI  - When the IACUC and AV don't agree, who wins?: Make the AV part of the plan.

PMID- 15861153
TI  - When the IACUC and AV don't agree, who wins?: Listen to the AV.

PMID- 15861154
TI  - Easily removed hair and skin in a newborn calf.

PMID- 15861156
TI  - Development of a body condition scoring system for nonhuman primates using Macaca
      mulatta as a model.
AB  - The nutritional status of individual monkeys in research projects is an important
      yet sometimes overlooked variable that complicates the interpretation of research
      findings. The authors offer a framework for scoring fatness and muscularity in a
      semiquantitative manner without special equipment and in a way that could easily
      be accomplished during a routine physical examination. Body condition scoring can
      be used to assess the health of individual animals as well as determine
      nutritional adequacy within groups of animals.

PMID- 15861157
TI  - Training nonhuman primates to perform behaviors useful in biomedical research.
AB  - Data collected from NHPs that are trained to participate voluntarily in
      husbandry, veterinary, and research procedures are likely to have particular
      value. The authors present the results of a series of studies that examined the
      effects of PRT on the performance by chimpanzees of a variety of biomedically
      relevant behaviors: presenting their perineum for pinworm testing, providing a
      semen sample, presenting for an s.c. injection, and presenting for an i.m.
      injection. The overall trends across studies indicate that PRT techniques have
      significant value in the handling and management of NHPs in many laboratory
      research settings, including less variability in the data collected and fewer
      potential confounding variables, which should lead to important refinements in
      the definition of NHPs as biomedical research models.

PMID- 15861158
TI  - Training captive chimpanzees to cooperate for an anesthetic injection.
AB  - Captive animals trained to cooperate with routine medical procedures, such as
      injections, may experience less aggression and anxiety than those forced to
      comply through the use of restraints. The authors used positive reinforcement
      training to teach captive chimpanzees to present a body part for anesthetic
      injection and determined the time investment necessary for initial training and
      duration of maintenance of the behavior after completion of the training.

PMID- 15861159
TI  - Assessment of personal protective equipment used for facial mucocutaneous
      exposure protection in nonhuman primate areas.
AB  - Animal caretakers working in NHP areas must wear facial PPE to protect themselves
      from the zoonotic hazards related to splash exposures, but PPE that is
      uncomfortable may present its own risks. The authors evaluated the level of
      protection offered by several types of facial PPE against a variety of simulated
      facial mucocutaneous exposures of the sort that could occur during typical
      procedures in Old World NHP facilities and determined that less restrictive PPE
      can be used without compromising safety.

PMID- 15861160
TI  - Evidence vs Experience in Neonatal Practice. Proceedings from the inaugural
      conference, October 8-9, 2004.

PMID- 15861161
TI  - Postnatal growth in preterm infants: have we got it right?
AB  - Postnatal growth retardation appears inevitable in preterm infants. This partly
      reflects an inability to establish adequate dietary intakes in a timely fashion
      in the sick, unstable immature infant. However, it may also reflect inherent
      errors in current recommendation as well as systematic errors in the way nutrient
      requirements are estimated in these high-risk infants. These issues are addressed
      in this article.

PMID- 15861162
TI  - Post-discharge nutrition of preterm infants.
AB  - The ever-increasing survival of premature and extremely low birth weight infants
      has posed a great challenge to neonatologists and nutritionists. While nutrient
      requirements are still being defined, there is a great need to continue to
      improve our strategies for providing effective nutrition for these infants.
      Similarly, postdischarge nutritional issues need to be addressed since catch-up
      growth does not always occur. In addition to fetal origins of adult diseases,
      especially cardiovascular disorders, diabetes and obesity, new data are emerging
      that postnatal growth alterations also affect these same disorders. However, as
      we learn more about the latter issues, one needs to be cautious about abandoning
      our current practices in providing optimal nutrition.

PMID- 15861164
TI  - Volume-targeted ventilation.
AB  - Recognition that volume, not pressure, is the key factor in ventilator-induced
      lung injury and awareness of the association of hypocarbia and brain injury
      foster the desire to better control delivered tidal volume. Recently,
      microprocessor-based modifications of pressure-limited, time-cycled ventilators
      were developed to combine advantages of pressure-limited ventilation with the
      ability to deliver a more consistent tidal volume. Each of the modes has
      advantages and disadvantages, with limited clinical data available to judge their
      effectiveness. The Volume Guarantee mode has been studied most thoroughly and is
      the only one that provides automatic weaning of peak pressure in response to
      improving lung compliance and patient respiratory effort. More consistent tidal
      volume, fewer excessively large breaths, lower peak pressure, less hypocarbia and
      lower levels of inflammatory cytokines have been documented. It remains to be
      seen if these short-term benefits will translate into shorter duration of
      ventilation or reduced incidence of chronic lung disease.

PMID- 15861165
TI  - Long-term programming effects of early nutrition -- implications for the preterm
      infant.
AB  - The current focus of nutritional science has shifted from meeting needs to
      determining the biological effects that nutrition has on immediate and lifetime
      health. Of particular interest is the concept of programming, the idea that "a
      stimulus or insult during a critical or sensitive period of development can have
      long-term or lifetime effects on an organism." Evidence that early nutrition has
      such "programming" effects in animals is overwhelming. In humans, retrospective
      observations show a relationship between adult disease and size in early life,
      though it is difficult to prove nutritional cause from observational associations
      and therefore difficult to use such data to underpin health policy. However, the
      results of randomized intervention trials of early nutrition with long-term
      follow-up are emerging. These experimental studies show that nutrition in early
      life has a major impact on health into early adulthood, notably on cardiovascular
      disease risk, bone health and cognitive function. These new findings have major
      biological, social and medical implications and should increasingly underpin
      health practices.

PMID- 15861166
TI  - Synchronized intermittent mandatory ventilation and pressure support: to sync or
      not to sync? Pressure support or no pressure support?
AB  - Mechanical ventilation has changed dramatically over the past few years with the
      explosion of technology. Asynchronous breathing is extremely common in intubated
      newborn infants. Asynchronous breathing has been shown to be associated with
      short-term adverse effects such as delivery of inconsistent tidal volume and
      minute ventilation, hypercarbia, hypoxemic episodes, increased energy
      expenditure, increased need for sedation and paralysis, decreased venous return,
      increase in intraventricular hemorrhage and fluctuations in blood pressure. It is
      now feasible to deliver synchronized breaths with the currently available
      ventilators to most patients in the newborn intensive care unit. Synchronized
      ventilation with pressure support of each spontaneous breath is physiological,
      decreases the work of breathing imposed by the endotracheal tube and has been
      shown to avoid most of the problems associated with asynchronous ventilation.

PMID- 15861168
TI  - Inotrope, lusitrope, and pressor use in neonates.
AB  - Successful management of neonatal shock is driven by the etiology and
      pathophysiology of the cardiovascular compromise. In the clinical practice,
      however, we only have a limited ability to recognize the etiology of the
      condition (hypovolemia, myocardial dysfunction or abnormal vasoregulation).
      Therefore, management is based on administration of fluid boluses and vasoactive
      medications according to personal preference rather than to the underlying
      pathophysiology. In addition, although management strategies aimed at improving
      systemic blood pressure may have been associated with a decrease in mortality in
      critically ill neonates, there are no prospective data on the effect of these
      management strategies on morbidity, especially on long-term neurodevelopmental
      outcome. This paper briefly reviews some of the more frequently encountered
      clinical presentations of neonatal shock and describes the developmentally
      regulated cardiovascular responses to the pathophysiology-driven management
      strategies used in these clinical presentations in the critically ill preterm and
      term neonate.

PMID- 15861169
TI  - Antenatal associations with lung maturation and infection.
AB  - Chronic clinically unapparent chorioamnionitis is a common antenatal exposure for
      very preterm infants, and these infants have variable degrees of lung maturation
      and a high risk of developing bronchopulmonary dysplasia. Exposure of fetal sheep
      to intra-amniotic endotoxin or IL-1alpha induces chorioamnionitis and lung injury
      (decreased alveolarization and microvascular injury), which resolves to a
      phenotype of striking lung maturation (increased surfactant, improved gas
      exchange and lung mechanics). The immune responses of the fetus also are
      suppressed or induced (matured) in time and dose-dependent ways by either
      chorioamnionitis or antenatal corticosteroids. These experimental observations
      contribute to explanations of why preterm infants have variable degrees of lung
      maturation at birth and unpredictably develop bronchopulmonary dysplasia BPD.

PMID- 15861170
TI  - Surfactant protein C: basics to bedside.
AB  - Development of clinically active synthetic surfactants has turned out to be more
      complicated than initially anticipated. Surfactant protein analogues must have
      the right conformation without forming oligomers. Furthermore, the lipid
      composition, as well as a high lipid concentration in the suspension seem to be
      important. For successful treatment of many respiratory diseases, it is desirable
      that the synthetic surfactant may stabilize the alveoli at end-expiration and may
      resist inactivation by components leaking into the alveoli.

PMID- 15861172
TI  - Overview of surfactant replacement trials.
AB  - Clinical trials have evaluated the overall efficacy of surfactant therapy, as
      well as the relative efficacy of different surfactant preparations, the optimal
      timing of administration and the optimal dosage. Surfactant therapy leads to
      significant clinical improvement in infants at risk for, or having, respiratory
      distress syndrome (RDS). Clinical trials that compared the effects of synthetic
      or animal-derived surfactant preparations to placebo or no therapy demonstrate
      that surfactant therapy lead to rapid improvement in oxygenation, decreased
      ventilator support, decreased risk of pneumothorax, and mortality. Earlier
      treatment, prophylactic treatment of infants at high risk of developing RDS, and
      selective re-treatment leads to improved clinical outcome as well. Currently
      available animal-derived surfactants are superior to non-protein-containing
      synthetic surfactants. Ongoing evaluation will determine if important differences
      in animal-derived products are noted. Future trials will evaluate third
      generation surfactant products and further refine what constitutes optimal use of
      surfactant.

PMID- 15861173
TI  - Oxygen for newborns: how much is too much?
AB  - International guidelines for newborn resuscitation recommend the use of 100%
      oxygen. However, high concentrations of oxygen after asphyxiation activate
      reactive oxygen species that may contribute to a number of morbidities. Animal
      models have been useful in describing their mechanisms, but only large-scale
      clinical trials can provide evidence that may be used to alter clinical practice.
      It has been demonstrated that neonates recover faster when resuscitated with room
      air as opposed to pure oxygen and neonatal mortality rates are improved.
      Increases in saturation are equal with oxygen and room air resuscitation. Studies
      of normal oxygen saturation immediately after birth suggest that clinicians may
      unnecessarily be rushing to high saturations. In the first weeks of life, lower
      saturation targets in preterm infants reduce retinopathy of prematurity and
      pulmonary complications and may improve growth. The neonatologist would be well
      served to think of oxygen as a medication, and use it sparingly.

PMID- 15861175
TI  - Pragmatic approach to in-hospital nutrition in high-risk neonates.
AB  - Extremely low birth weight infants may experience periods of moderate to severe
      undernutrition during the acute phase of their respiratory problems. This
      undernutrition contributes to early growth deficits in these patients and may
      have long-lasting effects, including poor neurodevelopmental outcome. Early
      postnatal intravenous amino-acid administration and early enteral feeding
      strategies will minimize the interruption of nutrient intake that occurs with
      premature birth. These two strategies will prevent intracellular energy failure,
      allow the administration of more non-protein energy, as well as enhance overall
      nutritional health, as evidenced by less postnatal weight loss and earlier return
      to birth weight, and improved overall postnatal growth and outcome.

PMID- 15861176
TI  - How long will chronic myeloid leukemia patients treated with imatinib mesylate
      live?

PMID- 15861177
TI  - Survival of chronic lymphocytic leukemia cells: CD40L and the vascular
      endothelial growth factor (VEGF) connection.

PMID- 15861178
TI  - Bedside RNA stabilizing kit systems for gene expression analysis of acute
      leukemias: influence of non-neoplastic white blood cells.

PMID- 15861179
TI  - Infectivity enhanced, hTERT promoter-based conditionally replicative adenoviruses
      are useful for SCLC treatment.
AB  - Treatment of advanced small-cell lung cancer (SCLC) remains one of the major
      challenges in current medicine because of the high morbidity and mortality of the
      disease. Advanced stage lung cancer is refractory to conventional therapies and
      it also has an extremely poor prognosis. As a result, new therapeutic approaches
      are needed. Telomere maintenance to the regulation of replicative lifespan
      strongly implies that alterations in telomere biology play an important role
      during malignant transformation. Cancers that exhibit high levels of telomerase
      activity, such as all of the SCLC, were examined in a previous study. In this
      study, we turned the expression of human telomerase reverse transcriptase (hTERT)
      by tumors to a therapeutic advantage using a conditionally replication-competent
      adenovirus (CRAd) in which the expression of E1 (early region 1) is controlled by
      the hTERT promoter. This virus achieved good levels of viral replication in SCLC
      cells and induced a substantial anticancer effect in vitro and in vivo. As a
      further enhancement, the cancer cell killing effect was improved with a tropism
      modification of the virus to express the knob domain of Ad3 (serotype 3
      adenovirus), and this improved infectivity for cancer cells. Conversely, the
      hTERT promoter has low activity in normal tissues, and the CRAd caused no damage
      to normal lung fibroblast cells. Since the telomerase activity is common in many
      types of cancers, these CRAds may be applicable to a wide range of tumors. We
      concluded that the use of hTERT promoter-based CRAds may be a potentially
      effective strategy for cancer treatment.

PMID- 15861180
TI  - From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome.
AB  - The mental retardation protein FMRP is involved in the transport of mRNAs and
      their translation at synapses. Patients with fragile X syndrome, in whom FMRP is
      absent or mutated, show deficits in learning and memory that might reflect
      impairments in the translational regulation of a subset of neuronal mRNAs. The
      study of FMRP provides important insights into the regulation and functions of
      local protein synthesis in the neuronal periphery, and increases our
      understanding of how these functions can produce specific effects at individual
      synapses.

PMID- 15861181
TI  - Neuronal variability: noise or part of the signal?
AB  - Sensory, motor and cortical neurons fire impulses or spikes at a regular, but
      slowly declining, rate in response to a constant current stimulus. Yet, the
      intervals between spikes often vary randomly during behaviour. Is this variation
      an unavoidable effect of generating spikes by sensory or synaptic processes
      ('neural noise') or is it an important part of the 'signal' that is transmitted
      to other neurons? Here, we mainly discuss this question in relation to sensory
      and motor processes, as the signals are best identified in such systems, although
      we also touch on central processes.

PMID- 15861182
TI  - Neural signatures of cell assembly organization.
AB  - Cortical neurons show irregular but structured spike trains. This has been
      interpreted as evidence for 'temporal coding', whereby stimuli are represented by
      precise spike-timing patterns. Here, we suggest an alternative interpretation
      based on the older concept of the cell assembly. The dynamic evolution of
      assembly sequences, which are steered but not deterministically controlled by
      sensory input, is the proposed substrate of psychological processes beyond simple
      stimulus-response associations. Accordingly, spike trains show a temporal
      structure that is stimulus-dependent and more variable than would be predicted by
      strict sensory control. We propose four signatures of assembly organization that
      can be experimentally tested. We argue that many observations that have been
      interpreted as evidence for temporal coding might instead reflect an underlying
      assembly structure.

PMID- 15861183
TI  - The rhythm of rest and excess.
AB  - There is a stark contrast between our attitudes to sleep and those of the pre
      industrial age. In Shakespeare's Julius Caesar we are told to "Enjoy the honey
      heavy dew of slumber". There seems little chance of this today, as we crave more,
      work more and expect more, and, in the process, abandon sleep. Our occupation of
      the night is having unanticipated costs for both our physical and mental health,
      which, if continued, might condemn whole sectors of our society to a dismal
      future.

PMID- 15861184
TI  - Chronic lymphocytic leukemic cells exhibit apoptotic signaling via TRAIL-R1.
AB  - Clinical trials have been initiated with Apo2L/TRAIL (Genentech) and agonistic
      mAbs to TRAIL receptors, -R1 and -R2 (Human Genome Sciences). The apoptosis
      inducing ability of these mAbs and different TRAIL preparations, in the presence
      or absence of histone deacetylase inhibitors (HDACi), varied markedly against
      primary chronic lymphocytic leukaemia (CLL) cells and various tumor cell lines,
      demonstrating an unanticipated preferential apoptotic signaling via either TRAIL
      R1 or -R2. Contrary to literature reports that TRAIL-induced apoptosis occurs
      primarily via signaling through TRAIL-R2, CLL cells, in the presence of HDACi,
      undergo predominantly TRAIL-R1-mediated apoptosis. Consequently, Apo2L/TRAIL,
      which signals primarily through TRAIL-R2, is virtually devoid of activity against
      CLL cells. To maximize therapeutic benefit, it is essential to ascertain whether
      a primary tumor signals via TRAIL-R1/-R2, prior to initiating therapy. Thus
      combination of an agonistic TRAIL-R1 Ab and an HDACi, such as the anticonvulsant
      sodium valproate, could be of value in treating CLL.

PMID- 15861185
TI  - Selective induction of DeltaFosB in the brain after transient forebrain ischemia
      accompanied by an increased expression of galectin-1, and the implication of
      DeltaFosB and galectin-1 in neuroprotection and neurogenesis.
AB  - Transient forebrain ischemia causes selective induction of DeltaFosB, an AP-1
      (activator protein-1) subunit, in cells within the ventricle wall or those in the
      dentate gyrus in the rat brain prior to neurogenesis, followed by induction of
      nestin, a marker for neuronal precursor cells, or galectin-1, a beta-galactoside
      sugar-binding lectin. The adenovirus-mediated expression of FosB or DeltaFosB
      induced expression of nestin, glial fibrillary acidic protein and galectin-1 in
      rat embryonic cortical cells. DeltaFosB-expressing cells exhibited a
      significantly higher survival and proliferation after the withdrawal of B27
      supplement than the control or FosB-expressing cells. The decline in the
      DeltaFosB expression in the survivors enhanced the MAP2 expression. The
      expression of DeltaFosB in cells within the ventricle wall of the rat brain also
      resulted in an elevated expression of nestin. We therefore conclude that
      DeltaFosB can promote the proliferation of quiescent neuronal precursor cells,
      thus enhancing neurogenesis after transient forebrain ischemia.

PMID- 15861186
TI  - Opening of plasma membrane voltage-dependent anion channels (VDAC) precedes
      caspase activation in neuronal apoptosis induced by toxic stimuli.
AB  - Apoptotic cell death is an essential process in the development of the central
      nervous system and in the pathogenesis of its degenerative diseases. Efflux of
      K(+) and Cl(-) ions leads to the shrinkage of the apoptotic cell and facilitates
      the activation of caspases. Here, we present electrophysiological and
      immunocytochemical evidences for the activation of a voltage-dependent anion
      channel (VDAC) in the plasma membrane of neurons undergoing apoptosis. Anti-VDAC
      antibodies blocked the channel and inhibited the apoptotic process. In
      nonapoptotic cells, plasma membrane VDAC1 protein can function as a NADH (
      ferricyanide) reductase. Opening of VDAC channels in apoptotic cells was
      associated with an increase in this activity, which was partly blocked by VDAC
      antibodies. Hence, it appears that there might be a dual role for this protein in
      the plasma membrane: (1) maintenance of redox homeostasis in normal cells and (2)
      promotion of anion efflux in apoptotic cells.

PMID- 15861187
TI  - Interplay between the NF-kappaB and forkhead transcription factors.

PMID- 15861188
TI  - Bak but not Bax is essential for Bcl-xS-induced apoptosis.
AB  - Bcl-x(S), a proapoptotic member of the Bcl-2 protein family, is localized in the
      mitochondria and induces apoptosis in a caspase- and BH3-dependent manner by a
      mechanism involving cytochrome c release. The way in which Bcl-x(S) induces
      caspase activation and cytochrome c release, as well as the relationship between
      Bcl-x(S) and other proapoptotic members of the Bcl-2 family, is not known. Here
      we used embryonic fibroblasts derived from mice deficient in the multidomain
      proapoptotic members of the Bcl-2 family (Bax and Bak) and the apoptotic
      components of the apoptosome (Apaf-1 and caspase-9) to unravel the cascade of
      events by which Bcl-x(S) promotes apoptosis. Our results show that Bak but not
      Bax is essential for Bcl-x(S)-induced apoptosis. Bcl-x(S) induced activation of
      Bak, which in turn promoted apoptosis by apoptosome-dependent and -independent
      pathways. These findings provide the first evidence that a proapoptotic Bcl-2
      family protein induces apoptosis exclusively via Bak.

PMID- 15861189
TI  - Isolation of gene sets affected specifically by polyglutamine expression:
      implication of the TOR signaling pathway in neurodegeneration.
AB  - Transcriptional dysregulation as a result of sequestration of essential
      transcription factors into protein aggregates formed by polyglutamine (polyQ)
      expansions can lead to late-onset progressive neurodegeneration. DNA microarray
      analysis of Drosophila expressing polyQ in the compound eye over time revealed
      large numbers of transcriptional changes at the earliest stages of the disease
      including repression of the transient receptor potential calcium channels in a
      polyQ-induced cell death specific manner. While significant differences in
      expression profiles were found between the Drosophila compound eye and polyQ
      sensitive neural cells, a number of possible key overlapping regulators were
      extracted. Among these, PDK1 was shown to act as a mediator for polyQ-toxicity,
      suggesting the involvement of the TOR pathway in polyQ-induced neurodegeneration.

PMID- 15861190
TI  - Cellular senescence mechanisms in chronic wound healing.

PMID- 15861191
TI  - ARC, an apoptosis suppressor limited to terminally differentiated cells, is
      induced in human breast cancer and confers chemo- and radiation-resistance.

PMID- 15861192
TI  - Nucleocytoplasmic transport in apoptosis.
AB  - The apoptotic demolition of the nucleus is accomplished by diverse proapoptotic
      factors, most of which are activated in the cytoplasm and gain access to the
      nucleoplasm during the cell death process. The nucleus is also the main target
      for genotoxic insult, a potent apoptotic trigger. Signals generated in the
      nucleus by DNA damage have to propagate to all cellular compartments to ensure
      the coordinated execution of cell demise. The nucleocytoplasmic shuttling of
      signalling and execution factors is thus an integral part of the apoptotic
      programme. Several proteins implicated in apoptotic cell death have been shown to
      migrate in and out of the nucleus following apoptosis induction. This review
      summarises the current knowledge on nucleocytoplasmic trafficking of apoptosis
      relevant proteins. The effects of apoptosis induction on the nucleocytoplasmic
      transport machinery are also discussed. Finally, a potential role of nuclear
      transport as a critical control point of the apoptotic signal cascade is
      proposed.

PMID- 15861193
TI  - Apoptotic cells quench reactive oxygen and nitrogen species and modulate TNF
      alpha/TGF-beta1 balance in activated macrophages: involvement of
      phosphatidylserine-dependent and -independent pathways.

PMID- 15861194
TI  - Daxx is required for stress-induced cell death and JNK activation.
AB  - Daxx has been implicated in the modulation of apoptosis in response to various
      stimuli. In the nucleus, Daxx interacts and colocalizes with the promyelocytic
      leukemia protein (PML) into the PML-nuclear body. Moreover, overexpressed Daxx
      positively modulates FAS-ligand and TGFbeta-induced apoptosis. However, recent
      reports indicate that Daxx can also act as an antiapoptotic factor. As most
      studies on the role of Daxx in cell death have been conducted using tumour cell
      lines, we analysed the function of Daxx in physiological settings. We found that
      Daxx is induced upon exposure to ultraviolet (UV) irradiation and hydrogen
      peroxide treatment. We employed RNA interference to downregulate Daxx in primary
      fibroblasts. Remarkably, Daxx-depleted cells are resistant to cell death induced
      by both UV irradiation and oxidative stress. Furthermore, the downregulation of
      Daxx results in impaired MKK/c-Jun-N-terminal kinase (JNK) activation. This is
      the first evidence that Daxx promotes cell death and JNK activation in
      physiological conditions.

PMID- 15861195
TI  - CMV acquisition in premature infants fed human milk: reason to worry?

PMID- 15861196
TI  - Heat loss prevention for preterm infants in the delivery room.
AB  - OBJECTIVE: Preterm infants are prone to hypothermia immediately following birth.
      Among other factors, excessive evaporative heat loss and the relatively cool
      ambient temperature of the delivery room may be important contributors. Most
      infants <29 weeks gestation had temperatures <36.4 degrees C on admission to our
      neonatal unit (NICU). Therefore we conducted a randomized, controlled trial to
      evaluate the effect of placing these infants in polyurethane bags in the delivery
      room to prevent heat loss and reduce the occurrence of hypothermia on admission
      to the NICU. METHODS: After parental consent was obtained, infants expected to be
      <29 weeks gestation were randomized to intervention or control groups just prior
      to their birth. Infants randomized to the intervention group were placed in
      polyurethane bags up to their necks immediately after delivery before being
      dried. They were then resuscitated per NRP guidelines, covered with warm
      blankets, and transported to the NICU, where the bags were removed and rectal
      temperatures were recorded. Control infants were resuscitated, covered with warm
      blankets, and transported without being placed in polyurethane bags. Delivery
      room temperatures were recorded so this potentially confounding variable could be
      assessed. RESULTS: Intervention patients were less likely than control patients
      to have temperature < 36.4 degrees C on admission , 44 vs 70% (p<0.01) and the
      intervention group had a higher mean admission temperature, 36.5 degrees C vs
      36.0 degrees C (p<0.003). This effect remained significant (p<0.0001) when
      delivery room temperature was controlled in analysis. Warmer delivery room
      temperatures (>/=26 degrees C) were associated with higher admission temperatures
      in both intervention and control infants, but only the subgroup of intervention
      patients born in warmer delivery rooms had a mean admission temperature >36.4
      degrees C. CONCLUSIONS: Placing infants <29 weeks gestation in polyurethane bags
      in the delivery room reduced the occurrence of hypothermia and increased their
      NICU admission temperatures. Maintaining warmer delivery rooms helped but was
      insufficient in preventing hypothermia in most of these vulnerable patients
      without the adjunctive use of the polyurethane bags.

PMID- 15861197
TI  - Dedicated neonatal retrieval teams improve delivery room resuscitation of outborn
      premature infants.
AB  - BACKGROUND: Morbidity related to ineffective resuscitation and stabilization of
      premature infants is increased when delivery occurs outside tertiary perinatal
      centers. The regional neonatal transport team received extensive training to
      expand their scope of practice to include delivery room resuscitation allowing
      them to attend high-risk deliveries in community hospitals when maternal transfer
      was not possible. OBJECTIVE: Compare the resuscitation and stabilization of
      premature infants when a specialized neonatal retrieval team (SNRT) is in
      attendance at delivery with immediate resuscitation and stabilization performed
      by the referral hospital team (RHT). STUDY DESIGN: We assessed the impact of a
      specially trained neonatal transport team by comparing the initial resuscitation
      process, airway and vascular access skills, illness severity and patient
      stabilization in both groups. RESULTS: Neonates resuscitated by the RHT were more
      likely to receive oxygen, mask CPAP, bag and mask ventilation and cardiac
      compressions for a significantly longer time period. Neonates resuscitated by the
      SNRT were intubated more promptly (8.5 minutes {1 to 22} vs 16 minutes {1 to 90},
      p=0.035) following a fewer number of attempts. The endotracheal tube was
      correctly positioned on radiological assessment in 72% of cases in the SNRT group
      vs 38.1% in the RHT group (p<0.001). Many neonates had no vascular access (31%)
      and were profoundly hypothermic (38.5%) on arrival of the SNRT. Although there
      was no significant difference in maximum FiO(2) or oxygenation index, babies with
      respiratory distress syndrome resuscitated by the RHT were less likely to receive
      surfactant therapy (76.6 vs 34.4%, p=0.001). There was no difference in transport
      related mortality between the groups CONCLUSIONS: The presence of a highly
      skilled transport team at a high-risk preterm delivery improves the quality of
      neonatal resuscitation by increasing intubation success rates and achieving
      earlier vascular access. Neonates resuscitated by dedicated neonatal retrieval
      teams were less likely to become significantly hypothermic. Although the severity
      of RDS was similar neonates in the RHT were less likely to receive surfactant.

PMID- 15861198
TI  - Outcome of very low birth weight infants exposed to antenatal indomethacin for
      tocolysis.
AB  - OBJECTIVE: Beginning in October 1995, and for several years thereafter, our
      institution used indomethacin as a first-line tocolytic drug. Our purpose is to
      compare the outcomes of very low birth weight infants who were exposed to
      antenatal indomethacin with those who were not exposed to this therapy. STUDY
      DESIGN: We used our center's component of the NICHD Neonatal Research Network's
      Generic Data Base which recorded the outcomes of all live born infants weighing
      less than 1500 g over a 5-year period. We abstracted data concerning neonatal
      morbidity (death, Grades III to IV intraventricular hemorrhage (IVH), necrotizing
      enterocolitis and patent ductus arteriosus), as well as other factors including
      gestational age, birth weight, antenatal corticosteroid treatment and maternal
      hypertension or pre-eclampsia. Univariate analysis was performed using Fisher's
      exact test. Multivariate analysis using logistic regression was performed to
      control for confounding factors. RESULTS: A total of 85 infants who were exposed
      to antenatal indomethacin were compared to 464 infants who were not exposed to
      the drug. In the univariate analysis, antenatal indomethacin exposure was not
      associated with a significant increase in the incidence of necrotizing
      enterocolitis or patent ductus arteriosus. The incidence of Grades III to IV IVH
      was 17.9% in those infants exposed to antenatal indomethacin compared to 7.1% in
      the nonexposed infants (p=0.008). The incidence of neonatal death in the exposed
      infants was 27.7 versus 16.4 in the nonexposed infants (p=0.02). After
      controlling for antenatal corticosteroids, maternal pre-eclampsia, gestational
      age and birth weight, antenatal indomethacin was significantly associated with an
      increased incidence of IVH, but not neonatal death. CONCLUSION: Antenatal
      indomethacin was associated with significantly higher rates of IVH. Additional
      studies assessing the potential risks of indomethacin tocolysis are needed before
      it is used as a first-line tocolytic therapy.

PMID- 15861199
TI  - Amniotic fluid: not just fetal urine anymore.
AB  - Amniotic fluid (AF) is a complex substance essential to fetal well-being. This
      article reviews recent discoveries and the current understanding of the origin
      and circulation of AF and its nutritive, protective, and diagnostic functions.
      Future directions for AF research are also discussed.

PMID- 15861200
TI  - PAGOD syndrome: a new abdominal finding and risk of sudden death.

PMID- 15861201
TI  - Successful intrauterine treatment with alcohol ablation in a case of acardiac
      twin pregnancy.
AB  - Acardiac twinning is a rare obstetric condition unique to monochorionic twin
      gestation and the pump twin has high perinatal mortality. We report an acardiac
      twin pregnancy, in which the pump twin presented with intrauterine growth
      restriction and oligohydramnios, and grossly hydropic acardiac fetus measured 12
      x 14 x 18 cm, and with no cardiac activity at 27 weeks of gestation. We treated
      the acardiac fetus with 1 ml alcohol ablation in utero, and delivered a live male
      baby weighing 1750 g at 36 weeks' gestation.

PMID- 15861202
TI  - Neonatal Gaucher disease presenting as persistent thrombocytopenia.
AB  - Mutations in the beta-glucocerebrosidase gene cause Gaucher disease with the type
      1 variant generally presenting later in life with mild disease and type 2 in
      infancy with severe neuronopathic symptoms. We describe a neonate homozygous for
      the D409 H mutation with thrombocytopenia, splenomegaly and cholestasis at birth
      as the major features.

PMID- 15861203
TI  - Severe hemolysis and hyperbilirubinemia due to perinatal napthalene exposure.

PMID- 15861205
TI  - Nasopharyngeal surfactant administration to prevent neonatal respiratory distress
      syndrome.

PMID- 15861207
TI  - Gardening the genome: DNA methylation in Arabidopsis thaliana.
AB  - DNA methylation has two essential roles in plants and animals - defending the
      genome against transposons and regulating gene expression. Recent experiments in
      Arabidopsis thaliana have begun to address crucial questions about how DNA
      methylation is established and maintained. One cardinal insight has been the
      discovery that DNA methylation can be guided by small RNAs produced through RNA
      interference pathways. Plants and mammals use a similar suite of DNA
      methyltransferases to propagate DNA methylation, but plants have also developed a
      glycosylase-based mechanism for removing DNA methylation, and there are hints
      that similar processes function in other organisms.

PMID- 15861208
TI  - Phylogenomics and the reconstruction of the tree of life.
AB  - As more complete genomes are sequenced, phylogenetic analysis is entering a new
      era - that of phylogenomics. One branch of this expanding field aims to
      reconstruct the evolutionary history of organisms on the basis of the analysis of
      their genomes. Recent studies have demonstrated the power of this approach, which
      has the potential to provide answers to several fundamental evolutionary
      questions. However, challenges for the future have also been revealed. The very
      nature of the evolutionary history of organisms and the limitations of current
      phylogenetic reconstruction methods mean that part of the tree of life might
      prove difficult, if not impossible, to resolve with confidence.

PMID- 15861209
TI  - Genetics of Crohn disease, an archetypal inflammatory barrier disease.
AB  - Chronic inflammatory disorders such as Crohn disease, atopic eczema, asthma and
      psoriasis are triggered by hitherto unknown environmental factors that function
      on the background of some polygenic susceptibility. Recent technological advances
      have allowed us to unravel the genetic aetiology of these and other complex
      diseases. Using Crohn disease as an example, we show how the discovery of
      susceptibility genes furthers our understanding of the underlying disease
      mechanisms and how it will, ultimately, give rise to new therapeutic
      developments. The long-term goal of such endeavours is to develop targeted
      prophylactic strategies. These will probably target the molecular interaction on
      the mucosal surface between the products of the genome and the microbial
      metagenome of a patient.

PMID- 15861211
TI  - Many little things: one geneticist's view of complex diseases.
AB  - Gene targeting is commonly used to knock out genes in order to understand their
      function. It has also been used successfully to model the relatively rare human
      genetic diseases that are caused by homozygous loss of gene function. Modelling
      the much more common multifactorial diseases that have strong genetic and
      environmental causes is less easy. Here, I describe my personal voyage into this
      challenging field, using gene targeting to alter the expression of genes that
      impact on hypertension and diabetes.

PMID- 15861212
TI  - Reliability of chromogenic in situ hybridization for detecting HER-2 gene status
      in breast cancer: comparison with fluorescence in situ hybridization and
      assessment of interobserver reproducibility.
AB  - Accurate determination of HER-2 status is important in the management of patients
      with breast cancer, especially in determining their eligibility for trastuzumab
      therapy. Fluorescence in situ hybridization (FISH) has been regarded as the gold
      standard method for detecting HER-2 gene amplification. Recently, chromogenic in
      situ hybridization (CISH), in which HER-2 is detected by a peroxidase reaction
      and the gene copies are determined by regular bright-field microscopy, has
      emerged as a potential alternative to FISH. However, this method requires
      validation before it can be adopted into clinical practice. In this study, we
      evaluated 80 cases of invasive breast carcinoma by CISH, compared the results
      with those obtained by FISH, and assessed interobserver reproducibility among
      three observers. We found that agreement among the three pathologists on the CISH
      determined HER-2 status was achieved in 73 cases (91%), all of which had results
      matching the corresponding FISH results: 54 nonamplified and 19 amplified. Of the
      19 amplified cases, 13 were scored unanimously as high-level amplification; six
      had a minor scoring discrepancy (ie, low-level vs high-level amplification). A
      major scoring discrepancy (ie, nonamplification vs amplification) was found in
      the remaining seven cases, three of which were amplified and four of which were
      nonamplified by FISH. Two of the latter cases had a polysomy of chromosome 17.
      The cases that caused scoring difficulty were those with an equivocal or
      borderline signal number against a high background. Overall, there was nearly
      perfect agreement between the CISH and corresponding FISH results, and
      interpretation of CISH results were highly reproducible among the three
      pathologists. We conclude that, in general, HER-2 status can be reliably assessed
      by CISH. Confirmatory FISH is recommended in cases with equivocal or borderline
      CISH copy numbers.

PMID- 15861213
TI  - Anatomic distribution and pathologic characterization of small-volume prostate
      cancer (<0.5 ml) in whole-mount prostatectomy specimens.
AB  - Some investigators consider small-volume prostate cancer (0.5 ml or less) without
      Gleason pattern 4/5 elements as clinically insignificant. The objective of this
      study was to characterize the anatomic distribution and pathologic features of
      small tumors (aggregate volume of 0.5 ml or less) in whole-mount prostatectomy
      specimens. Between 1999 and 2003, 371 consecutive patients underwent radical
      prostatectomy at the Indiana University Hospitals for localized prostate cancer.
      Patients who received hormonal or radiation therapy prior to the surgery were
      excluded from the study. A total of 62 specimens with total tumor volume of 0.5
      ml or less were identified and included in this study. All specimens were
      embedded and whole-mounted. Tumor volume was measured using the grid method. The
      mean age at the time of surgery was 59 years (median, 61 years; range, 37-72
      years). The mean preoperative prostate-specific antigen (PSA) was 6.5 ng/ml
      (range: 0.3-18 ng/ml). The mean prostate weight was 53 g (range: 16-132 g). The
      mean tumor volume was 0.29 ml (median, 0.35 ml; range, 0.02-0.48 ml). Tumor
      multifocality and bilaterality were present in 69 and 37% of cases, respectively.
      Three (5%) had positive surgical margins. The largest tumor was located in the
      peripheral zone, transitional zone, and central zone in 79, 16, and 5% of cases,
      respectively. The largest tumor was located in the anterior prostate in 10 cases
      (16%) and in the posterior prostate in 52 cases (84%). The distribution of
      Gleason scores was 5 (12 cases, 19 %), 6 (40 cases, 65 %), and 7 (10 cases, 16
      %). One case had a primary Gleason pattern 4. None had extraprostatic extension,
      seminal vesicle invasion, or lymph node metastasis. Small-volume prostate cancers
      are often multifocal and bilateral, with predilection for the peripheral zone. Of
      these small-volume cases, 16% had Gleason pattern 4 and might, therefore, be
      clinically significant.

PMID- 15861210
TI  - Mitochondrial DNA mutations in human disease.
AB  - The human mitochondrial genome is extremely small compared with the nuclear
      genome, and mitochondrial genetics presents unique clinical and experimental
      challenges. Despite the diminutive size of the mitochondrial genome,
      mitochondrial DNA (mtDNA) mutations are an important cause of inherited disease.
      Recent years have witnessed considerable progress in understanding basic
      mitochondrial genetics and the relationship between inherited mutations and
      disease phenotypes, and in identifying acquired mtDNA mutations in both ageing
      and cancer. However, many challenges remain, including the prevention and
      treatment of these diseases. This review explores the advances that have been
      made and the areas in which future progress is likely.

PMID- 15861214
TI  - High focal adhesion kinase expression in invasive breast carcinomas is associated
      with an aggressive phenotype.
AB  - Focal adhesion kinase (FAK) is a protein tyrosine kinase expressed in invasive
      breast cancer that regulates antiapoptotic signaling. We have examined FAK
      expression by immunohistochemistry using anti-FAK 4.47 in breast tumor samples
      from a large population-based, case-control study of women participating in the
      University of North Carolina Breast Specialized Programs of Research Excellence
      (SPORE), Carolina Breast Cancer Study. In this population, 629 formalin-fixed,
      paraffin-embedded tissue sections were stained for FAK and scored as high (3+ or
      4+ intensity and > or = 90% positive cells) or otherwise. High FAK expression was
      associated with poor prognostic indicators including high mitotic index (>10
      mitoses per 10 consecutive high-power fields), nuclear grade 3, architectural
      grade 3, estrogen and progesterone receptor negative, and HER-2/neu overexpressed
      using CB11 antibody. The association of high FAK expression with HER-2/neu
      overexpression lends further support that HER-2/neu and FAK collaborate to
      promote tumorigenesis. The presence of strong FAK expression in many high grade,
      estrogen- and progesterone-negative breast carcinomas indicates that FAK may be
      an attractive target for therapeutic intervention.

PMID- 15861215
TI  - Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic
      adenocarcinoma of colorectal origin.
AB  - Thyroid transcription factor-1 (TTF-1) is considered as a reliable marker for
      differential diagnosis in distinguishing primary adenocarcinomas of the lung from
      extrathoracic origins. We previously reported the first case of lung metastasis
      of colorectal origin, with nuclear expression of TTF-1. As most previous studies
      were performed on series of extrathoracic primary tumors, we raised the question
      of a possible role of lung microenviroment in TTF-1 expression. We investigated
      the rate of TTF-1 expression in lung metastases of extrathoracic adenocarcinomas
      and compared results of immunohistochemistry performed with different primary
      antibodies. Two different clones of antibodies (8G7G1/1 from Dako, SPT24 from
      Novocastra) raised against TTF-1 were used on 56 lung-metastatic malignant
      tumors, 41 from colorectal origin. A series of primary colorectal (90 cases) and
      primary pulmonary adenocarcinomas (86 cases) were also investigated. Four of 41
      (10%) lung metastases of colorectal adenocarcinomas displayed a nuclear staining
      for TTF-1 with SPT24 clone. Three of the four positive cases displayed similar
      nuclear staining in primary and/or other extrathoracic metastatic sites as well
      as four of 90 (5%) primary colorectal adenocarcinomas, ruling out the role of
      lung microenvironment. None of them was positive with 8G7G1/1 clone. Sensitivity
      between two sets of antibodies was compared in 86 primary pulmonary
      adenocarcinomas. Nuclear staining was detected in 72 cases (84%) with
      Novocastra's antibody and 56 cases (65%) with Dako's. Significant discordance was
      observed (P < 0.01). These results suggest that the diagnostic virtue of TTF-1
      detection depends on the used antibody's clone. The SPT24 clone seems to have a
      stronger affinity for TTF-1 protein but may lead to a few positive colorectal
      adenocarcinomas.

PMID- 15861216
TI  - Molecular assessment of allelic loss in Warthin tumors.
AB  - Warthin's tumors are benign lesions of the head and neck that have a
      characteristic morphologic appearance. The etiology of Warthin's tumors is
      controversial and whether they are true neoplasms or developmental malformations
      continues to be debated. In this study, we examined 12 Warthin tumors with a
      molecular and immunohistochemical approach. Immunostains for p53 and p16ink were
      performed. The epithelial and lymphoid components of each lesion were
      microdissected and PCR was performed for 13 microsatellite markers at or near
      common tumor suppressor genes. The results were analyzed semiquantitatively using
      capillary electrophoresis. Frequency of allelic loss was calculated. The
      epithelial component of all tumors was negative for p53 and p16ink. By molecular
      genotyping there was only one case that had one locus with allelic imbalance,
      while the remainder had no evidence of clonal allelic loss. The
      immunohistochemical and molecular results in this study lend support to the
      hypothesis that Warthin tumors are non-neoplastic, as there was no evidence of
      aberrant staining for tumor suppressor gene protein products and no evidence of
      consistent clonal allelic losses.

PMID- 15861217
TI  - Foraging behavior and prey interactions by a guild of predators on various
      lifestages of Bemisia tabaci.
AB  - The sweetpotato whitefly, Bemisia tabaci (Gennadius) is fed on by a wide variety
      of generalist predators, but there is little information on these predator-prey
      interactions. A laboratory investigation was conducted to quantify the foraging
      behavior of the adults of five common whitefly predators presented with a surfeit
      of whitefly eggs, nymphs, and adults. The beetles, Hippodamia convergens Guerin
      Meneville and Collops vittatus (Say) fed mostly on whitefly eggs, but readily and
      rapidly preyed on all of the whitefly lifestages. The true bugs, Geocoris
      punctipes (Say) and Orius tristicolor (Say) preyed almost exclusively on adult
      whiteflies, while Lygus hesperus Knight preyed almost exclusively on nymphs. The
      true bugs had much longer prey handling times than the beetles and spent much
      more of their time feeding (35-42%) than the beetles (6-7%). These results
      indicate that generalist predators vary significantly in their interaction with
      this host, and that foraging behavior should be considered during development of
      a predator-based biological control program for B. tabaci.

PMID- 15861218
TI  - Primary characterization and basal promoter activity of two hexamerin genes of
      Musca domestica.
AB  - Hexamerins are high molecular-weight proteins found in the hemolymph of insects
      and have been proposed to function as storage proteins. In previous studies, two
      Musca domestica hexamerins, designated Hex-L and Hex-F were characterized. Hex-L
      is synthesized exclusively by the larval fat bodies, is secreted into the
      hemolymph and likely provides a source of amino acids and energy during
      metamorphosis. Hex-F synthesis is induced by a proteinaceous meal and occurs only
      in the adult insect fat bodies. Hex-F also is secreted into the hemolymph and it
      has been suggested that in females it may be an amino acid reservoir to be used
      during the final stages of egg formation. Genomic clones containing full-length
      copies of the genes MdHexL1 and MdHexF1, encoding subunits of the larval and the
      adult female hexamerin, respectively, were isolated. Complete nucleotide
      sequences, including the 5'-end untranscribed regions, were determined and
      analyzed for each of the genes. Comparisons of the conceptual translation
      products of the cloned genes indicated that MdHexL1 and MdHexF1 are related to
      the larval serum proteins (LSP) 1 and 2 of Calliphora vicina and Drosophila
      melanogaster. DNA fragments containing the putative promoters of the two
      hexamerin genes were compared and cloned into a plasmid vector so as to drive the
      expression of the GFP reporter gene. The constructs were assayed in vitro in
      transfected S2 Drosophila melanogaster cells demonstrating that the cloned M.
      domestica DNA fragments exhibit promoter activity.

PMID- 15861219
TI  - Evaluating the impacts of refuge width on source-sink dynamics between transgenic
      and non-transgenic cotton.
AB  - Resistance management for Bt-transgenic crops relies in part on the production of
      sufficient numbers of susceptible insects in non-toxic refuges. Simulation models
      suggested that source-sink dynamics could interact with the structure of refuges
      to impact the production of insects in these areas. We tested the hypothesis that
      altering isolation between refuges and transgenic cotton by manipulating the
      width of refuges embedded within cotton fields would alter the density of
      Heliothis virescens and Helicoverpa zea eggs oviposited in refuges. Three
      categories of refuge widths were tested over two years: they included narrow (16
      24 m wide), medium (32-48 m wide) and wide (80-96 m wide) refuges. Isolation
      between the two habitats increased as refuge width increased. In 1996, eggs of H.
      virescens from H. zea were not distinguished, but a significant increase in the
      density of eggs and a significant decrease in relative yield (refuge yield
      compared to the yield from immediately surrounding Bt-cotton) was found as refuge
      width increased. In 1997, eggs from H. virescens were analyzed separately from H.
      zea using an ELISA test. The density of H. virescens eggs increased with
      increasing refuge width, and there was a significant decline in density of H.
      virescens eggs with increasing distance from the refuge. In contrast, there was
      no impact of refuge width on the density of H. zea eggs, nor was the slope of a
      regression of egg density and distance from the refuge significantly different
      from zero. We suggest that these differences reflect differences in the biology
      of the two insects.

PMID- 15861220
TI  - Bt transgenic crops do not have favorable effects on resistant insects.
AB  - Sayyed et al. (Ecology Letters (2003) 6: 167-169) hypothesized that insecticidal
      Bacillus thuringiensis (Bt) toxins produced by transgenic crops could have
      nutritionally favorable effects that increase the fitness of resistant insects
      eating such crops. This idea was based on increased pupal weight of resistant
      larvae of diamondback moth, Plutella xylostella (L.), fed leaf discs treated
      externally with a Bt toxin. We summarize evidence from diamondback moth and other
      pests showing that the Bt toxins in transgenic crops do not enhance performance
      of resistant insects. Aside from a few notable exceptions in which performance of
      resistant insects did not differ between Bt and non-Bt crops, Bt crops had
      adverse affects on resistant insects.

PMID- 15861221
TI  - Confirmation of bean leaf beetle, Cerotoma trifurcata, feeding on cucurbits.
AB  - The objective of these studies was to assess the degree to which bean leaf
      beetle, Cerotoma trifurcata (Forster), will feed on cucurbits. In 2003, we
      documented an infestation of C. trifurcata in a commercial pumpkin field near
      Rosemount, MN, USA. To evaluate C. trifurcata feeding on cucurbits, we conducted
      laboratory no-choice and choice test feeding studies. In the laboratory, C.
      trifurcata fed most heavily on cotyledon-stage cucumber plants, followed by
      pumpkin and squash. With soybean plants present, C. trifurcata still fed on
      cucumber plants. However, C. trifurcata appeared to prefer soybeans until the
      quality of the soybean plants was diminished through feeding damage. This is the
      first known report of C. trifurcata feeding on cucurbits. The pest potential of
      C. trifurcata in cucurbit cropping systems should be further evaluated.

PMID- 15861222
TI  - Cloning and expression of the VHDL receptor from fat body of the corn ear worm,
      Helicoverpa zea.
AB  - In Noctuids, storage proteins are taken up into fat body by receptor-mediated
      endocytosis. These include arylphorin and a second, structurally unrelated very
      high-density lipoprotein (VHDL). Previously, we have isolated a single storage
      protein receptor from the corn earworm, Helicoverpa zea, which binds both VHDL
      and arylphorin. The receptor protein is a basic, N-terminally blocked,
      approximately 80 kDa protein that is associated with fat body membranes.
      Microsequencing of proteolytic fragments of the isolated receptor protein
      revealed internal sequences that were used to clone the complete cDNA of the VHDL
      receptor by 3' and 5' RACE techniques. The receptor protein, when expressed in
      vitro via a suitable insect expression vector, reacted with antibodies against
      the native VHDL receptor and bound strongly to its ligand VHDL, thus confirming
      that the cloned cDNA represents indeed the previously purified VHDL receptor. The
      receptor protein and a second, similar protein also found associated with the fat
      body membrane show considerable homology to putative basic juvenile hormone
      suppressible proteins cloned previously from other Noctuid species. Sequence
      analysis revealed that the receptor is likely a peripheral membrane protein that
      may mediate the selective uptake of VHDL.

PMID- 15861223
TI  - NMR imaging of the honeybee brain.
AB  - NMR microscopy provides non-invasively distinct soft-tissue contrast in small
      biological samples. We were able to visualize the three-dimensional structure of
      the honeybee brain in its natural shape in the intact head capsule. Thus, in
      addition to acquiring detailed information about the shapes and volumes of the
      different brain compartments, we were able to show their relative orientations
      toward each other within the head capsule. Since the brain was lightly fixed but
      not dehydrated, and stayed attached to the head capsule and its internal
      structures, the NMR experiments exhibited larger volumes and a more natural
      stereo geometry of the various brain structures compared to confocal laser
      microscopy experiments on dissected, dehydrated and cleared brains.

PMID- 15861224
TI  - The prevalence of serum antibodies to tick-borne infections in Mbale District,
      Uganda: the effect of agro-ecological zone, grazing management and age of cattle.
AB  - Between August and October 2000, a cross-sectional study was conducted in
      smallholder dairy farms in Mbale District, Uganda to assess the prevalence of
      ticks and tick-borne diseases under different grazing systems and agro-ecological
      zones and understand the circumstances under which farmers operated. A
      questionnaire was administered to obtain information on dairy farm circumstances
      and practices. A total of 102 farms were visited and sera and ticks were
      collected from 478 animals. Sero-prevalence of tick-borne diseases was determined
      using an enzyme-linked immunoassay. Acaricides were used indiscriminately but the
      intensity of their use varied with the grazing system and zone. Cattle from
      different farms mixed for various reasons. During the dry seasons farmers have to
      get additional fodder from outside their farms that can result in importation of
      ticks. The prevalence of ticks and serum antibodies to tick-borne infections
      differed across the grazing systems and zones. The highest serum antibody
      prevalence (>60%) was recorded in the lowland zone under the free range and
      tethering grazing systems. The lowest tick challenge and serum antibody levels
      (<50%) were recorded in the midland and upland zones under a zero-grazing system.
      These findings suggest that endemic stability to East Coast Fever, babesiosis and
      anaplasmosis is most likely to have existed in the lowland zone, particularly,
      under the tethering and free-range grazing systems. Also, endemic stability for
      babesiosis existed in the upland zones. Endemic instability for East Coast Fever
      existed in the midland and upland zones. These structured observational studies
      are instrumental in planning of control strategies for ticks and tick borne
      diseases since production systems and the cattle population at high risk of the
      diseases in the district have been identified.

PMID- 15861225
TI  - New cell lines from Ephestia kuehniella: characterization and susceptibility to
      baculoviruses.
AB  - New cell lines from embryos of Ephestia kuehniella were recently developed.
      Primary cultures were initiated in September 2002 from 2 to 4 day old eggs in
      either modified TC-100 or ExCell 400 medium. From these initial cultures, one,
      originally isolated in the Ex-Cell medium, produced sufficient cell growth to
      allow subcultivation and eventually led to the establishment of two cell strains,
      one that forms multicellular vesicles in suspension and one consisting of tightly
      attached epithelial-like cells. The strains were compared to an extract from E.
      kuehniella eggs by isozyme analysis and shown to be from the same species. Both
      strains were inoculated with various insect viruses, including
      nucleopolyhedroviruses from Autographa californica, Anagrapha falcifera,
      Anticarsa gemmatalis, Galleria mellonella, Heliothis armigera, Helicoverpa zea,
      Lymantria dispar, Plutella xylostella, and Rachoplusia ou. Both strains were
      highly susceptible to most of the nucleopolyhedroviruses (with the exception of
      the viruses from Helicoverpa zea and Lymantria dispar which did not show
      cytopathology to either cell strain) with large numbers of occlusion bodies
      produced in most of the inoculated cells. Our results suggest these new lines can
      be useful in biocontrol research.

PMID- 15861226
TI  - Neotenic formation in laboratory colonies of the termite Coptotermes gestroi
      after orphaning.
AB  - The termite Coptotermes gestroi (Wasmann 1896) (Rhinotermitidae: Coptotermitinae)
      is an exotic species in Brazil and information concerning its reproductive
      developmental biology is scarce. We induced the formation of neotenics in
      laboratory colonies through orphaning experiments. Orphaning experiments were
      conducted in three-year old colonies of C. gestroi kept under laboratory
      conditions. After three months, eight nymphoid neotenics were observed in one
      colony after queen removal. Histological analysis showed that these neotenics
      were non-functional. The results suggest that these individuals may have arisen
      from the first nymphal instar (N1) or from an early N1 instar after one or two
      larval moults. Neotenics also were recorded on two incipient colonies of C.
      gestroi that lost the queen naturally.

PMID- 15861228
TI  - Distribution, spread, and ecological associations of the introduced ant Pheidole
      obscurithorax in the southeastern United States.
AB  - A field survey of the southeastern United States showed that Pheidole
      obscurithorax Naves, an ant introduced from South America, inhabits a 80-km-wide
      band along the coast between Mobile, Alabama, and Tallahassee, Florida, and is
      continuing to increase its range. In Tallahassee P. obscurithorax is rapidly
      spreading, and its nest density increased by a factor of 6.4 over a two-year
      period. Evidence suggests that P. obscurithorax has spread gradually by natural
      means. It coexists with the fire ant Solenopsis invicta Buren, appears to be part
      of a largely exotic community of ants that are tolerant of highly disturbed
      habitats, and seems to have little negative effect on the ant communities that it
      invades.

PMID- 15861227
TI  - Quantitative analysis of hemocyte morphological abnormalities associated with
      Campoletis sonorensis parasitization.
AB  - Endoparasitoids of arthropods evoke host cellular immune responses that result in
      hemocytic encapsulation of the endoparasitoid, unless these responses are
      disrupted by the parasite. Our interest has focused on mutualistic viruses found
      in some hymenopteran endoparasitoids that disrupt hemocyte function and prevent
      encapsulation. Specifically, the Campoletis sonorensis polydnavirus interacts
      with wasp factors to suppress immunity via expression of intracellular and
      secreted viral proteins. To study the roles of specific parasitization-associated
      factors on immunocyte morphology, fluorescence microscopy was used to visualize
      the actin cytoskeleton in infected and uninfected cells, or after treatment with
      C. sonorensis ovarian proteins or plasma from infected larvae. The titer and
      distribution of F- and G-actin were altered in hemocytes from parasitized insects
      relative to control cells, with plasma from parasitized larvae having an
      intermediate effect. This suggests that intracellular and secreted factors
      contribute to suppression of cellular immune responses in C. sonorensis.

PMID- 15861229
TI  - Oviposition of the invasive two-spotted leafhopper on an endemic tree: effects of
      an alien weed, foliar pubescence, and habitat humidity.
AB  - The two-spotted leafhopper, Sophonia rufofascia (Kuoh and Kuoh), is an exotic
      pest from South-East Asia that attacks a wide variety of plant species in Hawaii.
      Myrica faya Aiton is an aggressive exotic weed that displaces and excludes native
      plants in Hawaiian forests. It has been argued that because of the high
      nutritional quality of its foliage, M. faya might facilitate leafhopper invasion
      of native Hawaiian ecosystems that were originally dominated by the endemic tree
      Metrosideros polymorpha (Gaudichaud). In the present study, we quantified
      suitability of M. faya and M. polymorpha as ovipositional hosts for S.
      rufofascia. Overall, leafhoppers preferred to deposit their eggs into the foliage
      of M. faya. M. faya presence in the area did not affect leafhopper oviposition on
      M. polymorpha. Foliar pubescence provided good protection of hirsute morphotypes
      of M. polymorpha. At the same time, glabrous M. polymorpha morphotypes were quite
      suitable for leafhopper oviposition. There was no difference in the abundance of
      leafhopper eggs along a precipitation gradient. Our results confirm that invasion
      of native Hawaiian forests by the weed M. faya will facilitate their invasion by
      S. rufofascia. Because of the broad host range characteristic of the two-spotted
      leafhopper, this build-up may adversely affect a number of endemic plant species
      growing in native forests.

PMID- 15861230
TI  - The Pyrrhocoroidea (Hemiptera-Heteroptera) of the Ethiopian region.

PMID- 15861231
TI  - RNAi-induced silencing of embryonic tryptophan oxygenase in the Pyralid moth,
      Plodia interpunctella.
AB  - Gene silencing through the introduction of double-stranded RNA (RNA interference,
      RNAi) provides a powerful tool for the elucidation of gene function in many
      systems, including those where genomics and proteomics are incomplete. The use of
      RNAi technology for gene silencing in Lepidoptera has lacked significant
      attention compared to other systems. To demonstrate that RNAi can be utilized in
      the lepidopteran, Plodia interpunctella, we cloned a cDNA for tryptophan
      oxygenase, and showed that silencing of tryptophan oxygenase through RNAi during
      embryonic development resulted in loss of eye-color pigmentation. The complete
      amino acid sequence of Plodia tryptophan oxygenase can be accessed through NCBI
      Protein Database.

PMID- 15861232
TI  - Intraspecific competition in the speckled wood butterfly Pararge aegeria: effect
      of rearing density and gender on larval life history.
AB  - In insects, the outcome of intraspecific competition for food during development
      depends primarily upon larval density and larval sex, but effects will also
      depend on the particular trait under consideration and the species under study.
      Experimental manipulations of larval densities of a Madeiran population of the
      speckled wood butterfly Pararge aegeria confirmed that intraspecific competition
      affected growth. As densities increased P. aegeria adults were smaller and larval
      development periods were longer. Sexes responded differently to rearing density.
      Females were more adversely affected by high density than males, resulting in
      females having smaller masses at pupation. Survivorship was significantly higher
      for larvae reared at low densities. No density effect on adult sex ratios was
      observed. Intraspecific competition during the larval stage would appear to carry
      a higher cost for females than males. This may confer double disadvantage since
      females are dependent on their larval derived resources for reproduction as they
      have little opportunity to accumulate additional resources as adults. This
      suggests that shortages of larval food could affect fecundity directly. Males,
      however, may be able to compensate for a small size by feeding as adults and/or
      by altering their mate location tactics.

PMID- 15861233
TI  - DrawWing, a program for numerical description of insect wings.
AB  - There is usually a pattern of veins on an insect wing. This pattern is species
      specific and is used taxonomically. For example, the coordinates of some
      characteristic points on the wing are used to compare vein patterns. The
      characteristic points are often vein junctions or vein ends. A tool is presented
      that enables automatic identification of vein junctions. An image of an insect
      wing is used to determine the wing outline and veins. The vein skeleton is
      obtained using a thinning algorithm. Bezier splines are fitted to both the wing
      outline and the vein skeleton. The splines are saved in an encapsulated
      postscript file. Another output file in text format contains the coordinates of
      vein junctions. Both the program and its source code are available under GNU
      General Public License at [www.cyf-kr.edu.pl/~rotofils/drawwing.html]. The
      program presented in this paper automatically provides a numerical description of
      an insect wing. It converts an image of an insect wing to a list of coordinates
      of vein junctions, and a wing diagram that can be used as an illustration.
      Coordinates of the vein junctions extracted by the program from wing images were
      used successfully to discriminate between males of Dolichovespula sylvestris and
      Dolichovespula saxonica.

PMID- 15861234
TI  - Arthropod diversity in peas with normal or reduced waxy bloom.
AB  - Crop traits can alter economically important interactions between plants, pests,
      and biological control agents. For example, a reduced waxy bloom on the surface
      of pea plants alters interactions between pea aphids and their natural enemies.
      In this study, we assess whether the effect of wax reduction extends beyond the 2
      or 3 arthropod species closely associated with the plants and into the structure
      of the broader arthropod community of over 200 taxa at our site. We sampled
      arthropods on lines of peas with normal and reduced wax in Latah Co., Idaho using
      pitfall traps within randomly assigned pairs of 5 x 5 meter plots. During the
      1998 and 1999 growing seasons, we collected 12,113 individual arthropods from 221
      unambiguously identified morphospecies. The number of individuals collected from
      each morphospecies responded idiosyncratically to the reduced wax peas. To test
      whether arthropod community structure differed between the collections from plots
      having peas with normal or reduced wax, we performed a randomization test. The
      collection from peas with reduced wax had higher species evenness and thus higher
      community diversity despite having lower species richness. Our results
      demonstrate the potential of a single plant trait, epicuticular wax, to affect a
      community of arthropods. Two pests of peas had opposite responses to peas with
      reduced wax. The number of pea aphids collected was greater from peas with normal
      wax peas than those with reduced wax. In contrast, the number of pea leaf weevils
      collected was greater from peas with reduced wax.

PMID- 15861236
TI  - Culex quinquefasciatus (Diptera: Culicidae) as a potential West Nile virus vector
      in Tucson, Arizona: blood meal analysis indicates feeding on both humans and
      birds.
AB  - Most reports from the United States suggest Culex quinquefasciatus mosquitoes
      feed minimally on humans. Given the abundance of C. quinquefasciatus in
      residential Tucson and parts of metropolitan Phoenix, and the arrival of West
      Nile virus to this area, discovering the blood meal hosts of the local population
      is important. Using a sandwich ELISA technique, the local C. quinquefasciatus
      were found to feed on both humans and birds. This suggests they should be
      considered potential West Nile virus vectors.

PMID- 15861235
TI  - Entomopathogenic fungi for mosquito control: a review.
AB  - Fungal diseases in insects are common and widespread and can decimate their
      populations in spectacular epizootics. Virtually all insect orders are
      susceptible to fungal diseases, including Dipterans. Fungal pathogens such as
      Lagenidium, Coelomomyces and Culicinomyces are known to affect mosquito
      populations, and have been studied extensively. There are, however, many other
      fungi that infect and kill mosquitoes at the larval and/or adult stage. The
      discovery, in 1977, of the selective mosquito-pathogenic bacterium Bacillus
      thuringiensis Berliner israelensis (Bti) curtailed widespread interest in the
      search for other suitable biological control agents. In recent years interest in
      mosquito-killing fungi is reviving, mainly due to continuous and increasing
      levels of insecticide resistance and increasing global risk of mosquito-borne
      diseases. This review presents an update of published data on mosquito-pathogenic
      fungi and mosquito-pathogen interactions, covering 13 different fungal genera.
      Notwithstanding the potential of many fungi as mosquito control agents, only a
      handful have been commercialized and are marketed for use in abatement programs.
      We argue that entomopathogenic fungi, both new and existing ones with
      renewed/improved efficacies may contribute to an expansion of the limited arsenal
      of effective mosquito control tools, and that they may contribute in a
      significant and sustainable manner to the control of vector-borne diseases such
      as malaria, dengue and filariasis.

PMID- 15861237
TI  - The nest architecture of the Florida harvester ant, Pogonomyrmex badius.
AB  - The architecture of the subterranean nests of the Florida harvester ant,
      Pogonomyrmex badius, was studied through excavation and casting. Nests are
      composed of two basic units: descending shafts and horizontal chambers. Shafts
      form helices with diameters of 4 to 6 cm, and descend at an angle of about 15-20
      degrees near the surface, increasing to about 70 degrees below about 50 cm in
      depth. Superficial chambers (< 15 cm deep) appear to be modified shafts with low
      angles of descent, and are distinct from deeper chambers. In larger nests, they
      have a looping, connected morphology. Chambers begin on the outside of the helix
      as horizontal-floored, circular indentations, becoming multi-lobed as they are
      enlarged. Chamber height is about 1 cm, and does not change with area. Chamber
      area is greatest in the upper reaches of the nest, and decreases with depth.
      Vertical spacing between chambers is least in the upper reaches and increases to
      a maximum at about 70 to 80% of the maximum depth of the nest. The distribution
      of chamber area is top-heavy, with about half the total area occurring in the top
      quarter of the nest. Each 10% depth increment of the nest contains 25 to 40% less
      area than the decile above it, no matter what the size of the nest. Nests grow by
      simultaneous deepening, addition of new chambers and/or shafts and enlargement of
      existing chambers. As a result, the vertical spacing between chambers is similar
      at all nest sizes, and the relative distribution of chamber area with relative
      nest depth did not change during colony growth (that is, the size-free nest shape
      was the same at all colony sizes). Total chamber area increased somewhat more
      slowly than the population of workers excavating the nest. The branching of
      shafts was consistently shallow (< 40 cm), somewhat more so in large nests than
      small. Large colonies rarely had more than 4 shaft/chamber series. Each new
      series contributed less to the total chamber area because its chambers were
      smaller. Incipient colonies were usually 40 to 50 cm deep while mature colonies
      were commonly 2.5 to 3.0 m deep. Workers captured near the top of a mature nest
      (and therefore older) and penned in escape proof enclosures, excavated larger
      nests than did young workers captured from the bottom of the nest. Most of this
      difference was due to a larger fraction of older workers engaging in digging,
      rather than an increase in their rate of work. All ages of workers produced
      similar top-heavy nests. When different ages of workers from different levels of
      a mature colony were allowed to re-assort themselves in a vertical test apparatus
      buried in the soil, older workers moved upward to assume positions in the upper
      parts of the nest, much as in the colonies from which they were taken. The
      vertical organization of workers based on age is therefore the product of active
      movement and choice. A possible template imparting information on depth is a
      carbon dioxide gradient. Carbon dioxide concentrations increased 5-fold between
      the surface and the depths of the nest. A preference of young workers for high
      carbon dioxide concentrations, and a tendency for workers to dig more under low
      carbon dioxide concentrations could explain both the vertical age-distribution of
      workers, and the top-heaviness of the nest's architecture.

PMID- 15861238
TI  - The effect of the insecticide dichlorvos on esterase activity extracted from the
      psocids, Liposcelis bostrychophila and L. entomophila.
AB  - The inhibition kinetics of dichlorvos on carboxylesterase and
      acetylcholinesterase (AChE) activity extracted from Liposcelis bostrychophila and
      L. entomophila (Psocoptera: Liposcelididae) were compared. The results showed
      that L. entomophila had significantly greater specific activity of
      carboxylesterase than L. bostrychophila (0.045 versus 0.012 micromoles/mg/min).
      Moreover, the carboxylexterase of L. entomophila showed higher affinity (i.e.
      lower Km value) to the substrate 1-naphthyl acetate than L. bostrychophila (0.29
      versus 0.67 mM). The specific activity and affinity of AChE of the two species
      were not significantly different. The carboxylesterase of L. bostrychophila was
      more sensitive to the insecticide dichlorvos than that of L. entomophila. The
      I50s values of dichlorvos to carboxylesterase for L. bostrychophila and L.
      entomophila were 1.43 and 3.28 microM, respectively, and to AChE were 324 and 612
      nM, respectively. Inhibition kinetics revealed that AChE from L. bostrychophila
      was 5.8-fold more sensitive to inhibition than AChE from L. entomophila.

PMID- 15861239
TI  - Syspastospora parasitica, a mycoparasite of the fungus Beauveria bassiana
      attacking the Colorado potato beetle Leptinotarsa decemlineata: a tritrophic
      association.
AB  - A tritrophic association is reported, involving a Colorado potato beetle
      (Leptinotarsa decemlineata) infected with Beauveria bassiana, which in turn was
      infected with Syspastospora parasitica.

PMID- 15861240
TI  - Distinguishing the parasitic wasp, Peristenus howardi, from some of its congeners
      using polymerase chain reaction and restriction endonuclease digestion.
AB  - A molecular procedure incorporating polymerase chain reaction (PCR) of the COI
      gene and restriction endonuclease digestion of PCR products was used to
      distinguish Peristenus howardi (Hymenoptera: Braconidae) from four other
      Peristenus species. Non-solvent extraction of parasite DNA using a commercially
      available kit proved to be very effective in producing amplifiable template. Use
      of SfcI endonuclease produced restriction fragments with banding patterns in
      agarose gel electrophoresis that readily separated P. howardi, P. digoneutis, P.
      conradi, P. pallipes, and P. pseudopallipes. However, while the restriction
      fragment banding patterns of both P. pallipes and P. pseudopallipes were easily
      distinguishable from the other Peristenus species, they could not be reliably
      separated from one another. This molecular procedure can be used in applied and
      ecological research to better understand the role of P. howardi in the Peristenus
      Lygus parasite-host system within the Pacific Northwest. Consensus sequences of
      our amplimers for all five Peristenus spp. are deposited in GenBank.

PMID- 15861241
TI  - Protein-enriched pea flour extract protects stored milled rice against the rice
      weevil, Sitophilus oryzae.
AB  - Studies were conducted to evaluate the effect of a protein-enriched pea (Pisum
      sativum var. Bonneville) flour extract against the rice weevil, Sitophilus oryzae
      in its repellency, toxicity, effect on fecundity, stability and sensory
      properties. Milled rice admixed with pea flour extract at 1% concentration
      significantly repelled S. oryzae. Mortality of S. oryzae was found to increase
      and fecundity was markedly suppressed, in rice treated with 1% pea flour extract.
      The toxicity and reproductive effects of the pea protein-enriched rice were found
      to be stable for a period of 5 months. The sensory characteristics of stored rice
      when eaten were not affected by the treatment with pea flour extract. This study
      indicates that the protein-enriched flour extract obtained from the Bonneville
      pea may be feasible to protect stored milled rice from insect attack.

PMID- 15861242
TI  - The ants of North and Central America: the genus Mycocepurus (Hymenoptera:
      Formicidae).
AB  - We provide a review of the North American ants (north of Colombia) of the ant
      genus Mycocepurus, including keys to the workers and females, illustrations and
      distribution maps. The distribution of M. tardus is extended to Nicaragua and
      Costa Rica. The female of M. curvispinosus is described.

PMID- 15861244
TI  - Molecular structure of crude beeswax studied by solid-state 13C NMR.
AB  - 13C solid-state NMR experiments were performed to investigate the structure of
      beeswax in the native state (crude beeswax) for the first time. From quantitative
      direct polarization 13C MAS NMR spectrum, it was found that the fraction of
      internal-chain methylene (int-(CH2)) component compared to other components of
      crude beeswax was over 95%. The line shape of the int-(CH2) carbon resonance
      region was comprehensively analyzed in terms of NMR chemical shift. The 13C broad
      peak component covering from 31 to 35 ppm corresponds to int-(CH2) carbons with
      trans conformation in crystalline domains, whereas the sharp signal at 30.3 ppm
      corresponds to gauche conformation in the non-crystalline domain. From peak
      deconvolution of the aliphatic region, it was found that over 85% of the int
      (CH2) has a crystal structure and several kinds of molecular packing for int
      (CH2), at least three, exist in the crystalline domain.

PMID- 15861245
TI  - Habitat disturbance and the diversity and abundance of ants (Formicidae) in the
      Southeastern Fall-Line Sandhills.
AB  - We examined habitat disturbance, species richness, equitability, and abundance of
      ants in the Fall-Line Sandhills, at Fort Benning, Georgia. We collected ants with
      pitfall traps, sweep nets, and by searching tree trunks. Disturbed areas were
      used for military training; tracked and wheeled vehicles damaged vegetation and
      soils. Highly disturbed sites had fewer trees, diminished ground cover, warmer
      soils in the summer, and more compacted soils with a shallower A-horizon. We
      collected 48 species of ants, in 23 genera (141,468 individuals), over four years
      of sampling. Highly disturbed areas had fewer species, and greater numbers of
      ants than did moderately or lightly disturbed areas. The ant communities in
      disturbed areas were also less equitable, and were dominated by Dorymyrmex
      smithi.

PMID- 15861246
TI  - Demonstration of the protective effects of fluorescent proteins in baculoviruses
      exposed to ultraviolet light inactivation.
AB  - Autographa californica multiple nucleopolyhedrovirus (AcMNPV) recombinants,
      namely AcRFP produced by fusion of the red fluorescent protein (RFP) gene with
      the polyhedrin gene, and a recombinant (pAcUW21-23GFP) carrying the green
      fluorescent protein (GFP) in its viral envelope, were evaluated for their
      resistance to inactivation by ultraviolet light. AcRFP recombinants produced
      incomplete polyhedra with low infectivity for Trichoplusia ni larvae, whereas
      AcuW21-23GFP produced normal polyhedra with high infectivity. Electron microscopy
      of AcRFP CL14 showed the incorporation of very few viral particles into
      polyhedrin matrix protein material. The LC50 for AcuW21-23GFP was 0.10 occlusion
      bodies/mm2, whereas the LC50 values for several AcRFP recombinants ranged from 20
      to 329 occlusion bodies/mm2. When both the RFP and GFP recombinants were exposed
      to ultraviolet light (UV-B 280-320 nm), the results support the conclusion that
      these fluorescent proteins afford some protection against its damaging effects.

PMID- 15861247
TI  - Development of bollworms, Helicoverpa zea, on two commercial Bollgard cultivars
      that differ in overall Cry1Ac levels.
AB  - Research was conducted to quantify the development of the corn earworm (=
      bollworm), Helicoverpa zea (Boddie), on two different transgenic cotton cultivars
      (DP 50B and NuCOTN 33B) that contained different levels of the Cry1Ac endotoxin
      from the soil bacterium, Bacillus thuringiensis Berliner. Using a field cage, an
      inverse relationship between the amount of Cry1Ac among cultivars versus the
      weight of bollworm larvae was observed. Larvae that were recovered from the DP
      50B cultivar expressing lower Cry1Ac weighed significantly more than larvae
      collected from the higher expressing NuCOTN 33B cultivar. Cotton plants from
      NuCOTN 33B were measured as expressing 300% more Cry1Ac than DP 50B plants. The
      distribution of larval weights indicates that more late-instars (> 200 mg) were
      collected from the lower expressing DP50B cultivar than the higher expressing
      NuCOTN 33B cultivar. Within a single population, bollworm larvae were highly
      variable in their development when feeding on Bollgard cotton. Possible reasons
      and consequences for this variation are discussed.

PMID- 15861248
TI  - Influence of age and previous diet of Anopheles gambiae on the infectivity of
      natural Plasmodium falciparum gametocytes from human volunteers.
AB  - The effect of age and dietary factors of Anopheles gambiae (Diptera: Culicidae)
      on the infectivity of natural Plasmodium falciparum parasites was studied.
      Mosquitoes of various ages (1-3, 4-7 and 8-11 day old) and those fed blood
      (either single or double meals) and sugar meals were experimentally co-infected
      with P. falciparum gametocytes obtained from different naturally infected human
      volunteers. On day 7, midguts were examined for oocyst infection to determine
      whether mosquito age or diets have significant effects on parasite infectivity.
      The age of the mosquitoes did not significantly influence the oocyst infection
      rates (chi2 = 48.32, df = 40, P = 0.172) or oocyst load (# of oocysts/midgut) (P
      = 0.14) observed. Oocyst load between groups was not significantly different.
      Similarly, the type of diet (either blood or sugar) did not influence oocyst
      infection rates (chi2 = 16.52, df = 19, P = 0.622). However, an increase in
      oocyst infection rates resulted after previous feeding on double blood meals
      (35%) compared to single blood meals (25%), with comparable oocyst load. These
      observations are in agreement with those reported in previous studies suggesting
      that increased mosquito nutritional reserves resulting from increased dietary
      resources is favorable for malaria infectivity. This field-based study indicates
      that vector competence of An. gambiae to natural P. falciparum parasites does not
      vary with age and that nutritional resources acquired prior to an infectious
      blood meal plays a crucial role in mosquito-parasite relationships.

PMID- 15861249
TI  - Impact of pymetrozine on glassy-winged sharpshooter feeding behavior and rate of
      Xylella fastidiosa transmission.
AB  - Pymetrozine is a compound that interferes with insect feeding and interrupts
      transmission of plant pathogens. The glassy-winged sharpshooter, Homalodisca
      coagulata Say (Hemiptera, Cicadellidae), is a vector of Xylella fastidiosa, the
      foregut-borne, propagative bacterium that causes Pierce's disease of grapevine.
      In this study, we recorded the behavioral response of H. coagulata to plants
      treated by soil drench with pymetrozine using time-lapse photography, quantified
      the reduction in liquid excreta produced by H. coagulata fed on pymetrozine
      treated plants, and evaluated pymetrozine effectiveness in reducing transmission
      rate in grapevines. H. coagulata feeding on plants treated with 0.015 mg of
      pymetrozine was disrupted by decreasing the number of contacts made with the
      grapevine by more than 50% and by increasing movements away from the stem by more
      than 5-fold. Excreta production by H. coagulata was significantly reduced on
      plants treated with 0.015 or 0.0075 mg of pymetrozine. Contrary to the expected
      outcome, the mean number of X. fastidiosa-infected plants actually increased in
      the pymetrozine treatments relative to the controls.

PMID- 15861250
TI  - Geographic and voltinism differentiation among North American Ostrinia nubilalis
      (European corn borer) mitochondrial cytochrome c oxidase haplotypes.
AB  - DNA sequence of European corn borer, Ostrinia nubilalis (Hubner) (Lepidoptera:
      Crambidae), mitochondrial cytochrome c oxidase I (cox1) and II (cox2) genes were
      characterized and used for population genetic analysis. Twenty-six point
      mutations were identified from a 2,156 bp DNA sequence alignment. The frequency
      of polymorphic cox1DdeI and HaeIII, and cox2 Sau3AI and MspI restriction sites
      were determined from 1,414 individuals by polymerase chain reaction restriction
      fragment length polymorphism. Ten haplotypes were observed. A single haplotype
      was present among 90% of individuals examined, and a HaeIII haplotype was not
      present in samples from the Atlantic coast. Significant genetic differentiation
      existed between Atlantic coast and midwestern United States samples, and between
      sympatric uni- and bivoltine ecotypes. These genetic markers identify regional
      and ecotype differences in the North American O. nubilalis population.

PMID- 15861251
TI  - Infection behavior of a parasitoid fly, Emblemasoma auditrix, and its host cicada
      Okanagana rimosa.
AB  - Males of the cicada Okanagana rimosa (Homoptera: Cicadidae) that produce calling
      songs are parasitised by the parasitoid fly Emblemasoma auditrix (Diptera:
      Sarcophagidae). An ethogram of the infection behavior was extracted from
      videotaped experiments with tethered hosts. The infection behavior can be divided
      into three phases, each involving different sensory cues: long-range host
      detection via acoustic signals, visual short-range orientation, and a contact
      phase with tactile/chemical cues. After phonotaxis by flight, the fly lands on or
      near the host cicada. It walks around the host to identify the caudal end and
      squeezes underneath the wings (with a 64-67% preference of the left side).
      Finally, E. auditrix cuts into the timbal and deposits a larva into the sound
      producing organ of O. rimosa. This highly specific behavior restricts the host
      range to cicadas, only two species of which occur simultaneously with the
      parasitoid. During the infection behavior, the fly does not discriminate between
      male and female hosts. However, females were not successfully infected during the
      experiments. The host O. rimosa shows only weak defense behavior (mainly flapping
      their wings) and seems to rely on parasitoid avoidance. Production of the protest
      song does not prevent infection.

PMID- 15861252
TI  - Male accessory gland size and the evolutionary transition from single to multiple
      mating in the fungus-gardening ants.
AB  - Polyandry in hymenopteran social insects is surprisingly rare, despite its likely
      colony-level fitness benefits. Ordinarily, a male's fitness will be at odds with
      that of a colony when the genetic representation within it is diluted by multiple
      mating by the queen. Consequently, males are expected to be under selection to
      limit female re-mating, for example via secretions of their accessory glands. I
      hypothesized that if accessory glands in some way regulate female mating
      frequency, an evolutionary transition from single to multiple mating would likely
      be accompanied with a change in the morphology of the accessory glands. The
      accessory gland morphology was examined in the fungus-gardening ants, which have
      made a single transition from single to multiple mating. The evolution of
      polyandry within this clade corresponds to the loss of male accessory glands,
      lending tentative support to the idea that they may be involved in regulating
      mating frequency.

PMID- 15861253
TI  - Effect of different photoperiods on the growth, infectivity and colonization of
      Trinidadian strains of Paecilomyces fumosoroseus on the greenhouse whitefly,
      Trialeurodes vaporariorum, using a glass slide bioassay.
AB  - Growth, infectivity and colonization rates for blastospores and conidia of
      Trinidadian strains T, T10, and T11 of Paecilomyces fumosoroseus (Wize) Brown and
      Smith were assessed for activity against late fourth-instar nymphs of
      Trialeurodes vaporariorum (Westwood) (Homoptera:Aleyrodidae) under two different
      photoperiods (24 and 16 hour photophase). A glass-slide bioassay and a fungal
      development index, modified for both blastospores and conidia, were used to
      compare the development rates of the fungal strains on the insect hosts. Fewer
      adult whiteflies emerged from nymphs treated with blastospores and reared under a
      16:8 hour light:dark photoperiod than a 24:0 hour photoperiod. Eclosion times of
      whitefly adults that emerged from nymphs treated with the different strains of
      conidia were similar over the 8 day experimental period at both light regimes.
      The percent eclosion of adult whiteflies seems to be directly correlated with the
      speed of infection of the blastospore or conidial treatment and the photoperiod
      regime. The longer photophase had a significant positive effect on development
      index for blastospores; however, a lesser effect was observed for the conidia at
      either light regime. Blastospore strain T11 offered the most potential of the
      three Trinidadian strains against T. vaporariorum fourth-instar nymphs,
      especially under constant light. The glass-slide bioassay was successfully used
      to compare both blastospores and conidia of P. fumosoroseus. It can be used to
      determine the pathogenicity and the efficacy of various fungal preparations
      against aleyrodid pests.

PMID- 15861254
TI  - Molecular distinction between populations of Gonatocerus morrilli, egg
      parasitoids of the glassy-winged sharpshooter from Texas and California: do
      cryptic species exist?
AB  - Two molecular methods were utilized to distinguish geographic populations of
      Gonatocerus morrilli (Howard) from Texas and California and to test the
      possibility that this species could exist as a species-complex. Inter-Simple
      Sequence Repeat-Polymerase Chain Reactions (ISSR-PCR) were performed with a 5'
      anchored ISSR primer. Twenty-five markers were generated with four populations
      (40 individuals) of G. morrilli. Twenty-three were polymorphic and the percentage
      of polymorphic loci was 92%. Most markers could be considered diagnostic since
      there was no band sharing between the Texas and California populations. Such
      differences typically are not found unless the populations are reproductively
      isolated. Exact tests for population differentiation indicated significant
      differences in marker frequencies among the populations. Comparison of other
      genetic differentiation estimates, which evaluate the degree of genetic
      subdivision, demonstrated excellent agreement between GST and theta values, 0.92
      and 0.94, respectively, indicating that about 92 to 94% of the variance was
      distributed among populations. The average genetic divergence (D), as measured by
      genetic distance, was extremely high (Nei = 0.82 and Reynolds = 2.79). A
      dendrogram based on Nei's genetic distance separated the Texas and California
      populations into two clusters, respectively. Amplification of the Internal
      Transcribed Spacer-1 (ITS-1) region showed no size differences, whereas the ITS-2
      DNA fragment varied in size between the two geographic populations. The ITS-2
      fragment sizes were about 865 and 1099 base pairs for the California and Texas
      populations, respectively. The present study using the two molecular methods
      provides novel data critical to the glassy-winged sharpshooter/Pierce's disease
      biological control program in California.

PMID- 15861255
TI  - Seasonal abundance of the navel orangeworm, Amyelois transitella, in figs and the
      effect of peripheral aerosol dispensers on sexual communication.
AB  - We used flight traps baited with unmated female navel orangeworm Amyelois
      transitella (Walker) (Lepidoptera: Pyralidae) to examine, over two growing
      seasons, seasonal changes in the abundance of males in fig orchards and the
      impact of release of 48 mg per ha per day of the pheromone component (Z,Z)-11,13
      hexadecadienal from peripherally-located timed-release dispensers on the ability
      of males to find unmated females within 16-ha treatment plots. Material was
      placed out and mating disruption was commenced at the beginning of April in the
      first year, and at the beginning of July the second year. This technique
      effectively prevented males from finding females in female-baited traps placed
      throughout the plot. Navel orangeworm abundance was high in figs during the first
      and third flight, but lower in June and July during the second flight. Since
      Calimyrna figs are not susceptible to attack by navel orangeworm until mid-to
      late July, these findings suggest that materials cost can be reduced by beginning
      treatment later. Implications for insect pest management in figs and other
      California crops are discussed.

PMID- 15861256
TI  - Drug warranties and shared responsibility.

PMID- 15861257
TI  - Stress echocardiography in the evaluation of women presenting with chest pain
      syndrome: a randomized, prospective comparison with electrocardiographic stress
      testing.
AB  - OBJECTIVE: To evaluate the relative value of three stress testing modalities for
      establishing the presence of coronary artery disease in women presenting with
      chest pain. BACKGROUND: Echocardiographic testing modalities have the potential
      to be more effective than standard electrocardiographic stress testing (EST), but
      they require prospective evaluation. METHODS: Patients with no cardiac history
      and at least two cardiac risk factors were randomly assigned to one of three
      initial diagnostic strategies: treadmill EST (n=54), treadmill echocardiographic
      stress testing (ExE) (n=57) or dobutamine stress echocardiography (DSE) (n=47).
      Patients were followed prospectively for 28.1+/-14.2 months. The nature of the
      presenting chest pain was established clinically. RESULTS: Twelve patients (7.6%)
      were determined to have had cardiac chest pain, 128 patients (81.0%) received a
      diagnosis of noncardiac chest pain and 18 patients (11.4%) had indeterminate
      results. The echocardiographic testing modalities were associated with fewer
      indeterminate results than was EST (two of 104 [1.9%] versus 13 of 54 [24.1%]).
      All modalities were highly effective in excluding cardiac chest pain, with
      negative predictive values of 91.3%, 83.7% and 88.4%, respectively, for EST, DSE
      and ExE. The proportion of cases for which both definitive and accurate results
      were provided was 92.9% for DSE, 82.4% for ExE and 67.3% for EST. CONCLUSIONS:
      The results support the favourable prognosis of women presenting with chest pain
      syndrome and the reliability of negative results obtained with any of the testing
      modalities. Echocardiographic testing modalities are more likely than EST to
      provide both definitive and accurate results and would, therefore, seem to be the
      superior primary noninvasive testing modality in this patient population.

PMID- 15861258
TI  - Long-term outcome of cardiac resynchronization therapy in patients with severe
      congestive heart failure.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) has recently been shown to be
      an effective short-term therapy for patients with drug-refractory heart failure
      and intraventricular conduction delay. Little is known about the long-term
      effects of this therapy. OBJECTIVES: To determine the long-term outcome of all
      consecutive patients who underwent CRT at two Canadian centres, and to determine
      what baseline variables predict a response to CRT. RESULTS AND CONCLUSIONS: The
      present study comprised a total of 85 patients (mean age 66+/-9 years; 88% male)
      with New York Heart Association class II (4%), class III (84%) or class IV (12%)
      heart failure. All patients fulfilled the standard CRT indications with a QRS
      duration of 168+/-22 ms and a nuclear gated ejection fraction (EF) of 21+/-6%.
      Eighteen of the 85 patients were implanted with a combination automatic
      implantable cardioverter-defibrillator and CRT device. Within a mean clinical
      follow-up of 3.0+/-1.0 years, 26 of the 85 patients died, and eight patients
      underwent cardiac transplantation, with four transplant-related deaths (mean
      survival 3.53+/-0.26 years). Ten patients died of sudden cardiac death, eight
      patients died of progressive heart failure and eight patients died of noncardiac
      causes. None of the baseline factors (age, sex, EF, etiology, New York Heart
      Association class, QRS duration or implantable cardioverter-defibrillator) or
      indexes of CRT (change in EF or QRS duration) were predictive of a poor outcome.
      There was a clear trend for patients with a greater left ventricular EF gain to
      have a better outcome (P=0.1). The present observational data represent one of
      the longest follow-up databases of patients undergoing CRT. The significant
      morbidity and mortality found after CRT highlight the severity of the underlying
      cardiac pathology and concurrent illnesses.

PMID- 15861259
TI  - Long-term effectiveness of cardiac resynchronization therapy: Futile or useful?

PMID- 15861260
TI  - Patient reperfusion preferences in acute myocardial infarction: mortality versus
      stroke, benefits versus costs, high technology versus drugs.
AB  - BACKGROUND: Reperfusion therapy, thrombolysis and primary percutaneous coronary
      intervention (PCI) decrease mortality in ST elevation acute myocardial
      infarction. Tissue plasminogen activator (tPA) reduces the risk of death but at
      an increased risk of stroke and cost compared with streptokinase (SK). PCI
      reduces the risk of death and stroke compared with tPA, but at increased costs.
      The authors explored patient preferences for the various reperfusion strategies.
      PATIENTS AND METHODS: Among patients hospitalized with an acute coronary
      syndrome, preferences for tPA or SK were determined using a questionnaire based
      on Global Utilization of Streptokinase and Tissue Plasminogen Activator for
      Occluded Coronary Arteries (GUSTO-1) trial data including risk of death, stroke
      and the combination of the two. The impact of cost was assessed under the
      assumption of government or patient payment. Overall, the societal preference was
      solicited based on all the data. A similar survey was conducted comparing primary
      PCI with tPA using outcome data from a Cochrane review. RESULTS: When viewed in
      the context of net clinical benefit (NCB), 66.7% of patients chose tPA over SK.
      The preference for tPA diminished under the scenario of patient payment compared
      with government payment. However, as a societal strategy, the preference for tPA
      was 40.5% (P<0.001 versus NCB). Preference for primary PCI over tPA was strong
      whether based on risk of death (78.5%), stroke (88.1%) or NCB (95.4%). Cost
      considerations resulted in a slight fall in PCI preference (87.7%). As an overall
      societal strategy, 81.0% chose primary PCI over tPA (P=0.016 versus NCB). The
      preference for PCI was twice that for the most effective, but perhaps riskier,
      thrombolytic agent (tPA) (P<0.0001). CONCLUSIONS: Preference for the potentially
      inferior thrombolytic agent appears to depend on the lesser risk of stroke and
      the lower cost. Primary PCI was preferred by patients likely due to the lower
      risk of death and stroke, despite the increased cost. The preferences appeared to
      be influenced by societal costs. In addition, the allure and heightened
      expectations of high technology may play a role.

PMID- 15861261
TI  - Emergent decision-making: defining the patient perspective.

PMID- 15861262
TI  - Endothelin 1 versus endothelin 3 in the development of the slow force response to
      myocardial stretch.
AB  - BACKGROUND: Myocardial stretch promotes an increase in developed force (DF) in
      two phases: a rapid initial phase, and a slowly developing second phase called
      the slow force response (SFR) to myocardial stretch. The SFR results from an
      autocrine/paracrine mechanism of angiotensin II and endothelin (ET) release that
      is triggered by the stretch. OBJECTIVE: To explore whether exogenous ET-1 and/or
      ET-3 could mimic the SFR. METHODS: Experiments were performed in isometrically
      contracting (0.2 Hz) rat papillary muscles at 30 degrees C. DF was measured
      either after stretch or after the addition of ET-1 or ET-3 (in doses that
      increase contractility to a similar magnitude as does the SFR), with or without
      the selective ETA receptor antagonist BQ123 (300 nmol/L). RESULTS AND
      CONCLUSIONS: After 15 min, the SFR was 17.6+/-1.4% greater than the initial rapid
      phase (n=4; P<0.05) and was abolished by BQ123. ET-1 (5.0 nmol/L) increased DF by
      25.9+/-1.7% (n=4; P<0.05) after 30 min, an effect that was not altered by BQ123
      (22.6+/-3.9%; n=5). ET-3 (5.0 nmol/L) increased DF by 23.8+/-3.2% (n=5; P<0.05),
      an effect that was suppressed by BQ123 (-5.4+/-1.9%; n=5; P<0.05). Given that
      BQ123 eliminated the SFR and the inotropic response to ET-3 but not to ET-1, the
      results suggest that the SFR that follows myocardial stretch is due to the
      endogenous release of ET-3 acting in an autocrine/paracrine fashion.

PMID- 15861263
TI  - Sudden death and hypertrophic cardiomyopathy: a review.
AB  - Hypertrophic cardiomyopathy is a genetic disease that affects the cardiac
      sarcomere, resulting in myocardial hypertrophy and disarray. Affected patients
      have a predisposition for malignant ventricular tachyarrhythmias and,
      consequently, sudden cardiac death. With the availability of therapeutic measures
      that prevent sudden death, the identification of high-risk patients is now of
      greater importance. Clinical risk factors for sudden death (ie, age, syncope,
      family history of sudden cardiac death, cardiac arrest survivor, nonsustained
      ventricular tachycardia and abnormal blood pressure response to exercise) have
      been identified. The clinical electrophysiological study is of limited use for
      stratifying these patients. More recently, increased attention has been given to
      the degree of echocardiographically documented left ventricular hypertrophy and
      prognostically significant genetic mutations. Once a high-risk patient is
      identified, prophylactic treatment is warranted. For this purpose, amiodarone has
      been supplanted by the implantable cardioverter-defibrillator. Implantable
      cardioverter-defibrillator treatment appears to reduce the risk of sudden cardiac
      death in both primary and secondary prevention settings. Thus, tools are now
      available to identify and treat high-risk patients with hypertrophic
      cardiomyopathy.

PMID- 15861264
TI  - Separate origins of three coronary arteries arising from the right sinus of
      Valsalva.
AB  - A 58-year-old woman underwent coronary angiography because of chest pain on
      exertion. Her three coronary arteries arose from separate ostia in the right
      sinus of Valsalva. The left anterior descending coronary artery coursed between
      the great vessels, and the circumflex coronary artery coursed anterior to the
      pulmonary artery. Angiographic and clinical data of this rare anomaly are
      described.

PMID- 15861265
TI  - Nongastrointestinal symptoms of irritable bowel syndrome: an office-based
      clinical survey.
AB  - Irritable bowel syndrome (IBS) is the most prevalent gastrointestinal problem
      faced by practicing gastroenterologists. For many years, nongastrointestinal
      symptoms have been documented in IBS patients, but the medical literature does
      not emphasize them. The present study explored how IBS and inflammatory bowel
      disease patients differ in their reporting of nongastrointestinal symptoms.
      Information from 200 consecutive patients with IBS and a similar number of
      patients with Crohn's disease (in a single gastroenterology practice) was
      obtained at the initial visit using a simple questionnaire. Comparison of the
      data revealed that IBS patients describe certain nongastrointestinal symptoms far
      more frequently than do those with inflammatory bowel disease. It is recommended
      that these symptoms be considered along with the generally accepted criteria for
      making a positive diagnosis of IBS.

PMID- 15861266
TI  - Effects of formal education for patients with inflammatory bowel disease: a
      randomized controlled trial.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) suffer physical
      dysfunction and impaired quality of life (QOL), and need frequent health care.
      They often lack knowledge about their disease and desire more education.
      Educational interventions for other chronic diseases have demonstrated reduced
      health care use and increased knowledge, medication adherence and QOL. METHOD:
      Sixty-nine participants were randomly assigned to formal IBD education and
      standard of care (pamphlets and ad hoc physician education) or standard of care
      alone. Assessment of IBD knowledge and QOL occurred at baseline, immediately
      posteducation and eight weeks posteducation. Participants documented medication
      adherence and health care use in diaries. Patient satisfaction was assessed at
      the end of the study. RESULTS: The education group had higher knowledge scores
      (P=0.000), perceived knowledge ratings (P=0.01) and patient satisfaction
      (P=0.001). There was a lower rate of medication nonadherence and health care use
      for the education group, but the differences were not significant. QOL indices
      did not change. Significant correlations were found for increased health care use
      in patients with poorer medication adherence (P=0.01) and lower perceived health
      (P=0.05). CONCLUSION: Formal IBD patient education improves knowledge, perceived
      knowledge and patient satisfaction. Further study of long-term effects may better
      demonstrate potential benefits for QOL, medication adherence and health care use.

PMID- 15861267
TI  - Cross-sectional study of hepatitis B awareness among Chinese and Southeast Asian
      Canadians in the Vancouver-Richmond community.
AB  - BACKGROUND: Hepatitis B (HBV) is endemic and a leading cause of morbidity and
      mortality in Asia. British Columbia has the highest proportion of Chinese and
      Southeast Asians among all Canadian provinces. The present study was designed to
      evaluate the degree of concern for and knowledge of HBV in this high-risk
      community. METHODS: Unselected patrons of two large Asian commercial centres in
      Richmond, British Columbia were surveyed. The variables studied were population
      demographics, concern for HBV, level of HBV knowledge and awareness of HBV
      related cirrhosis or hepatocellular carcinoma (HCC). Associations were assessed
      using c2 testing and multiple logistic regression analysis. RESULTS: A total of
      1008 individuals participated in the survey. Fifteen incomplete surveys were
      excluded. Only 7.7% felt that HBV was not a concern for the community. Only 13%
      of respondents felt that HBV education was adequate in the community. The main
      sources of community health education were their doctor's office (56.3%) and
      media (49.1%). A high number stated they were "aware" of HBV (68%) but over 60%
      were unaware that HBV could cause HCC or cirrhosis and only 61.3% scored a
      'reasonable' level of HBV knowledge. Higher HBV knowledge was significantly
      associated with increasing age (P<0.001), higher education (P<0.001) and the use
      of media for health education (P<0.001). Awareness that HBV may cause HCC and
      cirrhosis was significantly associated with age (P<0.001), education (P=0.006)
      and birthplace (P=0.001). INTERPRETATION: HBV education is necessary in this
      local Asian community. Programs should target younger, less educated adults and
      elaborate on the potential serious health consequences of HBV. Vehicles for
      public education should include the physicians' offices and local media.

PMID- 15861268
TI  - Crohn's disease defined in three elderly sisters.
AB  - Three elderly sisters presented with symptomatic Crohn's disease. All had
      ileocolic involvement, and granulomatous inflammation was documented in
      endoscopic biopsies or surgically resected intestinal specimens. The present
      report documents the unusual occurrence of very late phenotypical expression of
      familial ileocolic Crohn's disease. The observations presented here reflect a
      possible gene-based predisposition to Crohn's disease or, alternatively, disease
      clustering related to a commonly shared environmental factor.

PMID- 15861270
TI  - Angiosarcoma of the gallbladder: case report and review of the literature.
AB  - A 62-year-old white woman with an unremarkable past medical history presented
      with acute cholecystitis. A cholecystectomy was performed, revealing an acute
      hemorrhagic and chronic cholecystitis associated with cholelithiasis. Two months
      after the operation, the patient developed a massive hemoperitoneum and died by
      hypo-volemic shock. At autopsy, an angiosarcoma measuring 5 cm in diameter was
      found in the liver, at the site of the gallbladder fossa. There were multiple
      hepatic, splenic, ovarian and peritoneal metastases and a massive hemoperitoneum
      consisting of 8 L of blood and blood clots. Review of the tissue sections from
      the patient's gallbladder confirmed the presence of an acute hemorrhagic and
      chronic cholecystitis and also revealed residual foci of an angiosarcoma. A
      review of eight previously reported cases of gallbladder angiosarcoma is also
      presented.

PMID- 15861269
TI  - A point mutation in the iron-responsive element of the L-ferritin in a family
      with hereditary hyperferritinemia cataract syndrome.
AB  - BACKGROUND: Hereditary hyperferritinemia cataract syndrome is an autosomal
      dominant condition that is characterized by a high serum ferritin level and
      bilateral early-onset cataracts in the absence of iron overload. The genetic
      abnormality is identified as a mutation in the 5' regulatory region of the L
      ferritin messenger RNA known as the iron-responsive element (IRE). The IRE
      controls ferritin synthesis in response to cytoplasmic iron pools by interacting
      with regulatory proteins called iron responsive proteins. Mutations in the IRE
      decrease its affinity for iron responsive proteins, leading to the constitutive
      synthesis of L-ferritin which results in hyperferritinemia and the intracellular
      accumulation of ferritin in the lens and eventual cataract formation. PATIENTS
      AND METHODS: A 22-year-old woman who was being investigated for hyperferritinemia
      was diagnosed with hereditary hyperferritinemia cataract syndrome after an
      extensive workup, including genetic testing for hemochromatosis and a liver
      biopsy to rule out iron overload. She developed anemia with phlebotomy treatments
      and subsequently developed symptomatic cataracts. The pedigree of her family
      affected with cataracts was consistent with an autosomal dominant transmission
      pattern. DNA was extracted from peripheral leukocytes of eight family members,
      four of whom were affected by cataracts. Polymerase chain reaction amplification
      of the 5' region of the L-ferritin gene was performed and a heterozygous point
      mutation (G32T) was identified in the bulge region of the IRE. CONCLUSION: The
      combination of early-onset cataracts and an elevated ferritin level should
      suggest this genetic syndrome.

PMID- 15861271
TI  - Are you willing to implicate villin in progressive cholestasis of childhood?

PMID- 15861272
TI  - [Guideline on radiation protection in medicine requires documentation of
      radioiodine therapy and follow-up: What are the benefits of an electronic
      database?].
AB  - AIM: The lately updated German guideline on radiation protection in medicine
      (Richtlinie Strahlenschutz in der Medizin) requires the physician who administers
      radioactive substances for therapy, to perform and document follow-ups. In order
      to decrease the administrative burden, an electronic database was developed that
      interfaces with a word processing software to generate written reports and
      statistic analysis. METHODS: Based on Microsoft Access and Microsoft Visual Basic
      a database was created to monitor patients with benign and malignant thyroid
      disorders after radioiodine therapy. It permits automatic creation of therapy
      documents and necessary patient reports in Microsoft Word. Intuitive handling,
      third level of normalization in database architecture and automatic plausibility
      checks guarantee integrity of the data and the efficacy of the database. RESULTS,
      CONCLUSION: The new software has been a success in over 1500 patients and over
      3800 in- and outpatient therapies and visits. The effort of data entry is easily
      offset by the automatic generation of the necessary patient reports. The required
      supervision of the follow-up appointments is now also user-friendly and
      efficient.

PMID- 15861273
TI  - [Where does subclinical hypothyroidism start? Implications for the definition of
      the upper reference limit for thyroid stimulating hormone].
AB  - The upper limit of the TSH reference range is currently under discussion. In its
      recent guidelines, the National Academy of Clinical Biochemistry (NACB)
      recommended the use of approximately 2.5 mIU/L, rather than approximately 4
      mIU/L, due to the fact that reference populations, on which the definition of the
      reference range is based, contain persons undergoing an initial phase of
      autoimmune thyroid disease. This will skew the upper reference limit of TSH.
      Ultrasonography, in addition to measurement of thyroid autoantibodies, should be
      used to exclude these persons. OBJECTIVE: The present study investigates whether
      the NACB recommendation also applies for a region of mild iodine deficiency.
      METHODS: According to NACB criteria, a reference population (713 persons) was
      defined out of a total study population of 1442. The TSH reference range was
      calculated in this reference group and in further subgroups by percentiles. The
      results were compared with the total study population and the NACB
      recommendation. All assays used were provided by BRAHMS Diagnostica AG,
      Hennigsdorf, Germany. RESULTS: As expected, all median TSH values, excluding the
      median of the group with a hypoechogenic thyroid were close to 1.2 mIU/L. The
      97.5th percentile in the reference population was 3.35 mIU/L. However, there was
      no difference compared to the total study population. CONCLUSION: The upper
      reference limit for TSH based on a reference population according to NACB
      criteria came down to 3.35 mIU/L, but not to approximately 2.5 mIU/L.
      Interestingly, there is no difference compared to the total study population.

PMID- 15861274
TI  - Scintigraphic results in patients with lung transplants: a prospective
      comparative study.
AB  - AIM: We addressed the feasibility of scintigraphy in the postoperative monitoring
      of lung transplants. METHOD: 37 patients (22 women, 15 men, 37 +/- 15 years) in
      good clinical condition were examined after lung transplantation. Scintigraphic
      procedures for assessing ventilation (133Xe), perfusion (99mTc microspheres) and
      aerosol-inhalation (99mTc aerosol) were performed for all patients. The findings
      were compared with those of established diagnostic modalities. RESULTS: All lung
      transplants showed homogeneous ventilation but with a non-physiologic difference
      of over 20% between both pulmonary lobes in one-third of the cases. There was a
      difference between the impairement of perfusion and ventilation in the presence
      of an impaired Euler-Liljestrand reflex in 14/37 (38%) patients. Furthermore,
      bronchoscopy and aerosol-inhalation scans often did not correlate, e. g. a
      bronchoscopically evident stenosis was not necessarily associated with an
      increased activity, and vice versa. Although peripheral mucociliary clearance was
      preserved after transplantation, stasis in central airways resulted in
      significantly impaired global clearance. CONCLUSION: Ventilation and perfusion
      scintigraphy reveal in a significant number of lung recipients pathologic
      findings and therefore can be recommended for postoperative monitoring. From a
      clinical point of view aerosol-inhalation scintigraphy (clearance) is not of any
      additional value.

PMID- 15861301
TI  - The proto-oncogene C-KIT maps to canid B-chromosomes.
AB  - Plant and animal karyotypes sometimes contain variable elements, that are
      referred to as additional or B-chromosomes. It is generally believed that B
      chromosomes lack major genes and represent parasitic and selfish elements of a
      genome. Here we report, for the first time, the localization of a gene to B
      chromosomes of mammals: red fox (Vulpes vulpes) and two subspecies of raccoon dog
      (Nyctereutes procyonoides). Identification of the proto-oncogene C-KIT on B
      chromosomes of two Canidae species that diverged from a common ancestor more than
      12.5 million years ago argues against the current view of B-chromosomes. Analyses
      of fox B-chromosomal C-KIT gene from a flow-sorted fox B-chromosome-specific
      library revealed the presence of intron-exon boundaries and high identity between
      sequenced regions of canine and fox B-chromosomal C-KIT copies. Identification of
      C-KIT gene on all B-chromosomes of two canid species provides new insight into
      the origin and evolution of supernumeraries and their potential role in the
      genome.

PMID- 15861302
TI  - A whole-arm translocation (WAT8/9) separating Sumatran and Bornean agile gibbons,
      and its evolutionary features.
AB  - Gibbons, like orangutans, are a group of threatened Asian apes, so that genetic
      monitoring of each species or subspecies is a pressing need for conservation
      programmes. We conducted a project to take, as far as possible, samples of known
      origin from wild-born animals from Sumatra and Borneo (Central Kalimantan) for
      genetic monitoring of agile gibbons. As a result, we found a whole arm
      translocation between chromosomes 8 and 9 (WAT8/9) specific to Sumatran agile
      gibbons. Furthermore, population surveys suggested that the form with the WAT8/9
      seems to be incompatible with an ancestral form, suggesting that the former might
      have extinguished the latter from Sumatran populations by competition. In any
      case, this translocation is a useful chromosomal marker for identifying Sumatran
      agile gibbons. Population genetic analyses with DNA showed that the molecular
      genetic distance between Sumatran and Bornean agile gibbons is the smallest,
      although the chromosomal difference is the largest. Thus, it is postulated that
      WAT8/9 occurred and fixed in a small population of Sumatra after migration and
      geographical isolation at the last glacial period, and afterwards dispersed
      rapidly to other populations in Sumatra as a result of the bottleneck effect and
      a chromosomal isolating mechanism.

PMID- 15861303
TI  - Different populations of RNA polymerase II in living mammalian cells.
AB  - RNA polymerase II is responsible for transcription of most eukaryotic genes, but,
      despite exhaustive analysis, little is known about how it transcribes natural
      templates in vivo. We studied polymerase dynamics in living Chinese hamster ovary
      cells using an established line that expresses the largest (catalytic) subunit of
      the polymerase (RPB1) tagged with the green fluorescent protein (GFP). Genetic
      complementation has shown this tagged polymerase to be fully functional.
      Fluorescence loss in photobleaching (FLIP) reveals the existence of at least
      three kinetic populations of tagged polymerase: a large rapidly-exchanging
      population, a small fraction resistant to 5,6-dichloro-1-beta-D
      ribofuranosylbenzimidazole (DRB) but sensitive to a different inhibitor of
      transcription (i.e. heat shock), and a third fraction sensitive to both
      inhibitors. Quantitative immunoblotting shows the largest fraction to be the
      inactive hypophosphorylated form of the polymerase (i.e. IIA). Results are
      consistent with the second (DRB-insensitive but heat-shock-sensitive) fraction
      being bound but not engaged, while the third (sensitive to both DRB and heat
      shock) is the elongating hyperphosphorylated form (i.e. IIO).

PMID- 15861304
TI  - The evolutionary origin of insect telomeric repeats, (TTAGG)n.
AB  - The (TTAGG)n sequence is supposed to be an ancestral DNA motif of telomeres in
      insects. Here we examined the occurrence of TTAGG telomeric repeats in other
      arthropods and their close relatives by Southern hybridization of genomic DNAs
      and fluorescence in-situ hybridization (FISH) of chromosomes with (TTAGG)n probes
      or, alternatively, with the 'vertebrate' telomeric probe, (TTAGGG)n. Our results
      show that the (TTAGG)n motif is conserved in entognathous hexapods (Diplura and
      Collembola), crustaceans (Malacostraca, Branchiura, Pentastomida, and
      Branchiopoda), myriapods (Diplopoda and Chilopoda), pycnogonids, and most
      chelicerates (Palpigradi, Amblypygi, Acari, Opiliones, Scorpiones,
      Pseudoscorpiones, and Solifugae) but not in spiders (Araneae). The presence of
      TTAGG repeats in these groups suggests that the sequence is an ancestral motif of
      telomeres not only in insects but in Arthropoda. We failed, however, to detect
      the TTAGG repeats in close relatives of the arthropods, Tardigrada and
      Onychophora. But while Onychophora had the 'vertebrate' (TTAGGG)n motif instead,
      the Tardigrada did not. The (TTAGG)n motif probably evolved from the (TTAGGG)n
      motif. Based on our and compiled data, we presume that the 'vertebrate' motif
      (TTAGGG)n is an ancestral motif of telomeres in bilaterian animals and possibly
      also in the superclade including animals, fungi and amoebozoans.

PMID- 15861305
TI  - Cytogenetic studies of Hynobiidae (Urodela) XIX. Morphological variation of sex
      chromosomes pairing behavior of sex lampbrush chromosomes in Hynobius
      quelpaertensis (Mori) from Cheju Island, South Korea.
AB  - Using Giemsa staining, C-banding and Ag-NOR staining techniques, we analyzed
      chromosomes in adult male and female Hynobius quelpaertensis and in embryos of
      this species in egg sacs collected from eight localities of Cheju Island, South
      Korea. Chromosome pair 21 was consistently homomorphic in male specimens, while
      it was heteromorphic in female specimens, suggesting the occurrence of ZZ/ZW sex
      chromosome constitution in this species. The W chromosome, being much larger than
      the Z chromosome, was of three morphologically distinct types: WA, WB and WC.
      Lampbrush chromosomes examined in the oocytes of one female specimen having the
      WA chromosome showed that the short arm of the WA chromosome and the long arm of
      the Z chromosome paired closely and hence are genetically homologous. We also
      tried to analyze the structural relationship among the three types of W
      chromosomes based on their C-banding and Ag-NOR patterns.

PMID- 15861306
TI  - The topology of early- and late-replicating chromatin in differentially
      decondensed chromosomes.
AB  - In this study we used a novel technique to reveal both longitudinal and
      transverse differentiation within mammalian mitotic chromosomes. Structural
      changes in chromosomes that we term 'differential decondensation' were produced
      in cells that were first incubated in hypotonic medium (15% Hanks' solution),
      then adapted to normotonic conditions and thereafter exposed to a second short
      hypotonic shock. Such a double hypotonic treatment (DHT) is not critical for cell
      viability, but considerably elongates the G2 phase of the cell cycle. Giemsa
      staining of differentially decondensed chromosomes corresponds to standard G
      banding, but does not need the standard post-fixation treatment. Using 'dynamic'
      BrdU banding, we show that such 'differential' staining is a result of
      differential resistance of the R- and G-bands to DHT. Thus, early-replicating
      foci, markers of R-bands, are localized in the peripheral chromatin halo, whereas
      late-replicating foci, corresponding to G-bands, remain associated with the axial
      regions of chromatids. Remarkably, despite these major changes in the structure
      of the chromosomal bands, the replication foci still preserve their discrete
      structure.

PMID- 15861307
TI  - The replication timing of CFTR and adjacent genes.
AB  - Correlations between transcriptional activity and replication timing have been
      observed for the human cystic fibrosis transmembrane conductance regulator (CFTR)
      gene, as well as for other tissue-specific genes. In addition, the patterns of
      histone modifications and the nuclear positioning of chromosomal loci appear to
      be related to their replication timing. It is not understood why and how these
      different features are functionally linked. To address this problem, we
      investigated the replication timing of the human CFTR gene and of adjacent genes.
      Recently, we could show that CFTR and adjacent genes associate independently from
      each other with different nuclear regions and chromatin fractions, in accordance
      with their individual transcriptional regulation. Together, the results show that
      not the transcriptional activity, but rather the nuclear position of CFTR and
      adjacent genes appears to be a major determinant of their replication timing.
      Furthermore, the results imply a specific functional order of nuclear changes
      related to switches in replication timing.

PMID- 15861308
TI  - Characterization of CENH3 and centromere-associated DNA sequences in sugarcane.
AB  - Centromere-specific histone H3 (CENH3) has been used to detect active
      centromeres, and to analyse the DNA sequences closely associated with the
      centromere, because they localize only in active centromeres and bind directly to
      the DNA. In maize and rice, the centromeric retrotransposons (CR) are shown to be
      closely associated with their own CENH3 whereas no such association was found in
      Arabidopsis thaliana. In this study, this sort of association was investigated in
      sugarcane. Two expressed sequence tag groups encoding putative sugarcane CENH3
      (SoCENH3) were found in a sugarcane-expressed sequence tag database. Their
      deduced amino acid sequences were similar to these of the CENH3s in rice and
      maize. An antibody against rice CENH3 seemed to crossreact with the SoCENH3s, and
      stained sugarcane centromeres. A set of immunoprecipitation tests was conducted
      with the antibody and chromatin from the sugarcane genome to reveal CENH3
      associated DNA sequences in sugarcane. Centromeric tandem repeats (SCEN) and
      centromeric retrotransposons of sugarcane (CRS) were significantly precipitated
      with the antibody, meaning these repeats are directly interacting with CENH3 in
      sugarcane centromeres.

PMID- 15861309
TI  - Female-specific hyperacetylation of histone H4 in the chicken Z chromosome.
AB  - Birds undergo genetic sex determination using a ZW sex chromosome system.
      Although the avian mechanisms of neither sex determination nor dosage
      compensation are understood, a female-specific non-coding RNA (MHM) is expressed
      soon after fertilisation from the single Z chicken chromosome and is likely to
      have a role in one or both processes. We have now discovered a prominent female
      specific modification to the Z chromatin in the region of the MHM locus. We find
      that chicken chromatin at Zp21, including the MHM locus, is strongly enriched for
      acetylation of histone H4 at lysine residue 16 in female but not male
      chromosomes. Interestingly, this specific histone modification is also enriched
      along the length of the up-regulated Drosophila melanogaster male X chromosome
      where it plays a vital role in the dosage compensation process.

PMID- 15861310
TI  - Integration of the cytogenetic and physical maps of chicken chromosome 17.
AB  - The chicken genome, like those of most avian species, contains numerous
      microchromosomes that cannot be distinguished by size alone. Unique properties
      attributed to the microchromosomes include high GC content and gene density, and
      an enhanced recombination rate. Previously, microchromosome GGA 17 was shown to
      align with the consensus genetic linkage group E41W17, and bacterial artificial
      chromosome (BAC) clones containing E41W17 markers were isolated and assigned on
      the physical BAC map as well as the recently assembled draft chicken genome
      sequence. For this study, these same BACS were utilized as probes for
      fluorescence in-situ hybridization (FISH) to develop the GGA 17 cytogenetic map.
      Here we detail the chromosome order of ten BAC DNAs, thereby deriving a
      cytogenetic map of GGA 17 that is simultaneously integrated with both the linkage
      map and genome sequence. The location of the FISH probes together with the
      morphological appearance of the chromosome suggested that GGA 17 is an
      acrocentric chromosome whose cytogenetic map orientation is reversed from that
      currently indicated by the linkage map and draft genome sequence. The reversed
      orientation and the centromere location of GGA 17 were confirmed experimentally
      by dual-colour FISH hybridization using terminal BACs and the centromere-specific
      CNM oligonucleotide as probes. An advantage of this cyto-genomic approach is the
      improved alignment of the sequence and linkage maps with cytogenetic features
      such as the centromere, telomeres, p and q arms, and staining patterns indicating
      GC versus AT content.

PMID- 15861311
TI  - Statins effect on smooth muscle cell proliferation.
AB  - Clinical trials have firmly established that 3-hydroxy-3-methylglutaryl-coenzyme
      A reductase inhibitors (statins) can induce regression of vascular
      atherosclerosis as well as reduction of cardiovascular-related morbidity and
      death in patients with and without coronary artery disease. These beneficial
      effects of statins are usually assumed to result from their ability to reduce
      cholesterol synthesis. However, because mevalonic acid is the precursor not only
      of cholesterol but also of many nonsteroidal isoprenoid compounds, inhibition of
      3-hydroxy-3-methylglutaryl-coenzyme-A reductase may result in pleiotropic
      effects. Indeed, statins can interfere with major events involved in the
      formation and the evolution of atherosclerotic lesions, such as arterial myocyte
      migration and proliferation and cholesterol accumulation, independent of their
      hypolipidemic properties. The aim of this article is to focus on clinical and
      experimental data that show that statins possess effects beyond cholesterol
      lowering, particularly on arterial smooth muscle cell proliferation. The
      contribution of these direct vascular effects to the reduction of cardiovascular
      events observed in clinical trials with statins represents one of the major
      challenges for future studies to understand the antiatherosclerotic benefits of
      these agents.

PMID- 15861313
TI  - The spectrum of statin therapy in hyperlipidemic children.
AB  - The recommended therapy of hypercholesterolemia in children consists of dietary
      modification and bile acid-binding resins. Unfortunately, the lipid-lowering
      efficacy of bile acid-binding resins is modest, and moreover, long-term
      compliance is poor because of side effects. In contrast, hydroxymethylglutaryl
      coenzyme A reductase inhibitors (statins) are widely used in adults and are
      considered to be the first choice in the treatment of hypercholesterolemia in
      that age category. In the last few years, several randomized trials have been
      conducted to evaluate the efficacy, safety, and tolerability of statin therapy in
      both children and adolescents. In this article, we review statin therapy in
      hypercholesterolemic children in terms of efficacy, safety, pharmacokinetics, and
      psychosocial functioning. Statins are not only effective in reducing low-density
      lipoprotein cholesterol levels in children with familial hypercholesterolemia but
      also improve endothelial function and reduce the progressive thickening of the
      intima media complex of the carotid arteries. Statins seem safe at the longer
      term in children in terms of plasma levels of liver enzymes and liver function,
      creatine kinase levels, and muscle function, as well as growth and sexual
      development. Long-term follow-up studies are needed to assess whether statin
      treatment started early in children with familial hypercholesterolemia can
      prevent future cardiovascular events.

PMID- 15861314
TI  - Statins and diabetes.
AB  - Lipid abnormalities play an important part in raising the cardiovascular risk in
      diabetic subjects. The main components of diabetic dyslipidemia are increased
      plasma triglycerides, low concentration of high-density lipoprotein cholesterol,
      preponderance of small, dense low-density lipoprotein, and excessive postprandial
      lipemia. Small, dense low-density lipoprotein, the elevation in remnant
      triglyceride-rich lipoprotein particles, and the low high-density lipoprotein are
      the most powerful atherogenic components. The coexistence of these three factors
      strongly aggravates the lipid accumulation in the arterial wall and the formation
      of atherosclerotic plaques. The position of diabetes in cardiovascular risk
      assessment has been recently reviewed in the Harmonized Clinical Guidelines on
      Prevention of Atherosclerotic Vascular Disease. In general, patients with
      diabetes carry a high risk for cardiovascular disease, but the absolute risk
      varies depending on the type of diabetes, age, and population baseline risk. The
      Adult Treatment Program III (ATP III) and the American Heart Association have
      designated diabetes as a high-risk condition and recommended intensive risk
      factor management. Concerning therapeutic targets, both ATP III and the American
      Diabetes Association (ADA) guidelines have identified low-density lipoprotein
      cholesterol as the first priority of lipid lowering, and the optimal level was
      set at less than 2.6 mmol/L (100 mg/dL). There is strong evidence, coming from
      landmark secondary prevention studies, that LDL lowering in people with diabetes
      is associated with significant clinical benefits. The benefits of statin therapy
      in type 2 diabetics can no longer be questioned. Ongoing clinical trials will
      help clarify the question of whether increasing high-density lipoprotein
      cholesterol with fibrates in the presence of low low-density lipoprotein levels
      (lower than 3.4 mmol/L, or 130 mg/dL) will be more beneficial than statin therapy
      alone. The new paradigms in risk-reduction therapies for type 2 diabetic subjects
      are focused on cardiovascular disease prevention, rather than only on glucose or
      lipid control. Therapeutic lifestyle changes are considered primary therapies for
      hyperglycemia and coexisting metabolic syndrome, which can be diagnosed in more
      than half of type 2 diabetes subjects. New perspectives of lipid management in
      type 2 diabetes should take into account that insulin resistance, increased
      lipolysis, and overproduction of large, buoyant, very low density lipoprotein
      particles are at the base of diabetic dyslipidemia. Accordingly, drugs acting in
      the regulatory steps of very low density lipoprotein assembly should be
      developed. Activation of peroxisome proliferator activated receptor alpha
      (PPARalpha), as occurs with fibrates, lowers free fatty acids (FFAs) and
      triglyceride levels. PPARgamma agonism, as demonstrated by the
      thiazolidinediones, increases triglyceride lipolysis, FFA transport, and
      conversion of FFAs to triglycerides. As separate activation of PPARalpha and
      PPARgamma improves lipid metabolism, the development of new drugs integrating
      PPARalpha and PPARgamma activity (PPAR-alpha/gamma agonists) is a promising line
      that may further improve insulin resistance, FFA metabolism, and consequently,
      atherogenic diabetic dyslipidemia.

PMID- 15861315
TI  - Statins and endothelial dysfunction.
AB  - The endothelium integrates and modulates critical functions of the arterial wall.
      As well as regulating vasomotion, it controls inflammation, coagulation, and
      thrombosis. Many of these actions are mediated through the release of nitric
      oxide. Endothelial dysfunction is associated with atherosclerosis and its risk
      factors. It is independently correlated to adverse cardiovascular events,
      including myocardial infarction, coronary death, and the need for
      revascularization. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      (statins) protect against cardiovascular death, myocardial ischemia, myocardial
      infarction, and stroke. Although cholesterol reduction accounts for some of these
      benefits, others appear to be independent of cholesterol lowering. The
      endothelium mediates many of these "lipid-dependent" and "lipid-independent"
      actions of statins. This chapter reviews the effects of statins on endothelial
      dysfunction. To do so, a brief outline of the biology of the endothelium is a
      prerequisite. This will be followed by a summary of the advances in vascular
      research on cholesterol-dependent and cholesterol-independent effects of statins,
      with a focus on the endothelium. Ultimately, clinical relevance of observations
      derived from basic biology will be discussed.

PMID- 15861316
TI  - Lipid lowering therapy in atherosclerosis.
AB  - Dyslipidemia plays critical roles in the pathogenesis of coronary
      atherosclerosis, a chronic inflammatory disease. Vascular inflammation also
      triggers the onset of acute complications of atherosclerosis, such as myocardial
      infarction. Advances in cardiovascular medicine demonstrate that lipid-lowering
      therapy by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins)
      likely prevents acute coronary complications by limiting vascular inflammation.
      In particular, recent clinical evidence indicates aggressive lipid-lowering
      treatment for patients at risk. Preclinical studies also support the concept of
      anti-inflammatory properties of lipid lowering by either diet or statins.
      Therefore, dyslipidemia is the primary target of therapy for the prevention of
      coronary atherosclerosis and its acute thrombotic complications. Nevertheless,
      even aggressive statin therapy does not forestall many adverse events. Thus,
      current cardiovascular medicine also seeks mechanisms to mitigate vascular
      inflammation and atherosclerosis other than addressing low-density lipoprotein,
      and new therapeutic strategies beyond lipid lowering.

PMID- 15861317
TI  - Statins and hypertension.
AB  - Hypertension and dyslipidemia are frequently associated as risk factors for
      cardiovascular diseases. Statins are among the most potent drugs to correct
      hypercholesterolemia, and their use across a wide range of cardiovascular risk
      levels significantly reduced morbidity and mortality in large intervention
      trials. Aside from (or in addition to) reducing plasma cholesterol, statins also
      reduce blood pressure, another effect associated with cardiovascular risk
      reduction by other antihypertensive drugs. This review examines the proposition
      that a part of the statins' beneficial effect in cardiovascular diseases may
      result from direct effects on blood pressure regulation, perhaps independent of
      lipid lowering. Potential molecular mechanisms are considered (e.g.,
      "pleiotropic" effects on endothelial vasoactive mediators, oxidant stress, or
      inflammation), all of which may affect the central or peripheral control of blood
      pressure homeostasis, as well as modulate target organ damage. In particular,
      potential effects of statins on blood pressure and heart rate variability open
      new perspectives for a better tailoring of drug treatment in high-cardiovascular
      risk patients.

PMID- 15861319
TI  - Effects of statins on endothelium and endothelial progenitor cell recruitment.
AB  - Statins appear to be potent drugs with a variety of pleiotropic effects with
      vasculoprotective and cardioprotective activity. The beneficial effects of
      statins on endothelial cells as well as on endothelial cell function appear to be
      related to improved nitric oxide bioavailability. Mechanistically, statins induce
      endothelial nitric oxide synthase mRNA stability in endothelial cells and promote
      endothelial nitric oxide synthase activity through a PI3K/Akt dependent pathway,
      which is a common signal transduction pathway shared by growth factors such as
      vascular endothelial growth factors or fibroblast growth factors (FGFs),
      estrogens, or statins. Furthermore, statins have potent antiinflammatory
      capacities by potently interfering with the generation of reactive oxygen species
      or activating scavenging systems for free radicals such as the thioredoxin
      system. These mechanisms might all contribute to improved NO bioavailability and
      confer the beneficial actions of statins. The proangiogenic properties of statins
      and their effects on reendothelialization following vessel injury include novel
      actions such as the mobilization, differentiation, and improved survival of
      endothelial progenitor cells. Statin therapy might reverse the impaired
      functional regeneration capacities seen in patients with risk factors for
      coronary artery disease or documented active coronary artery disease by
      specifically interacting with progenitor cell function. Accordingly, augmentation
      of functionally active endothelial progenitor cells with improved homing capacity
      will be a critical step in advancing therapeutic neovascularization as well as
      reendothelialization in patients with coronary artery disease.

PMID- 15861318
TI  - Statins and the myocardium.
AB  - Cardiac hypertrophy and heart failure are leading causes of morbidity and
      mortality worldwide. The 3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors, or statins, have been shown to inhibit cardiac hypertrophy and
      improve symptoms of heart failure by cholesterol-independent mechanisms. Statins
      block the isoprenylation and function of members of the Rho GTPase family, such
      as Rac1 and RhoA. Because Rac1 is a requisite component of NADPH oxidase, which
      is a major source of reactive oxygen species in cardiovascular cells, the ability
      of statins to inhibit Rac1-mediated oxidative stress contributes importantly to
      their inhibitory effects on cardiac hypertrophy. Furthermore, inhibition of RhoA
      by statins leads to the activation of protein kinase B/Akt and upregulation of
      Type 3 nitric oxide synthase in the endothelium and the heart. This activation
      and upregulation results in increased angiogenesis and myocardial perfusion,
      decreased myocardial apoptosis, and improvement in endothelial and cardiac
      function. Because these effects of statins occur independent of cholesterol
      lowering, statins may have therapeutic benefits in nonhyperlipidemic patients
      with cardiac hypertrophy and heart failure.

PMID- 15861320
TI  - The pro- and antiangiogenic effects of statins.
AB  - Clinical studies indicate that 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitor (statin) therapy has a cardiovascular protective activity
      that may result from an improvement in endothelial function. Experimental studies
      have shown that statins protect against ischaemia-reperfusion injury of the heart
      and stimulate the growth of new blood vessels in ischemic limbs of
      normocholesterolemic animals. The mechanisms underlying these serum lipid
      independent effects of statins are not completely understood, but there is
      increasing evidence that they improve endothelial function through molecular
      mechanisms that mediate an increase in endothelium-derived nitric oxide. Recent
      research has revealed a link between statins and the serine/threonine protein
      kinase Akt that regulates multiple angiogenic processes in endothelial cells,
      including the generation of nitrous oxide. In contrast to these data, it has also
      been reported that higher doses of statins inhibit endothelial cell migration and
      angiogenesis. Thus, further studies on the actions of statins may lead to the
      identification of new pharmacological targets for the control of blood vessel
      growth.

PMID- 15861321
TI  - Statins and cardiac allograft vasculopathy after heart transplantation.
AB  - Coronary artery disease in the transplanted heart, also known as cardiac
      allograft vasculopathy, is one of the major causes of mortality late after heart
      transplantation. There are multiple immune and nonimmune risk factors associated
      with this disease process, one of which is hyperlipidemia. Use of lipid-lowering
      agents, specifically 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      (statins) was initially reported to have outcomes benefit and possibly
      immunosuppressive effects in a single-center study of heart transplant
      recipients. Other subsequent studies have supported this beneficial effect.
      Hyperlipidemia is associated with immune activity, particularly with respect to
      oxidation-sensitive signaling pathways. By lowering lipids, statins can
      ameliorate this immune activity, but it has been a matter of contention as to
      whether statins have cholesterol-independent immune-modulating effects. In two
      recent papers, cholesterol-independent immune effects of statins have been
      reported, including repressed induction of major histocompatibility complex class
      II by interferon-gamma, and selective blocking of leukocyte function antigen 1,
      both of which reduce the activation of T lymphocytes. The clinical reports
      demonstrating outcomes benefits in heart transplant recipients and recent
      laboratory publications that report an immunomodulatory effect of statins provide
      a firm scientific rationale to support the routine use of statins in heart
      transplant patients.

PMID- 15861322
TI  - Statins in atherothrombosis.
AB  - Clinical studies have shown that hydroxy-methyl glutaryl coenzyme A reductase
      inhibitors (statins) may favorably affect atherothrombosis. In addition to their
      potent cholesterol-lowering properties, statins reduce atheroma progression as
      well as the incidence of acute thrombosis-related vascular events and their
      dreadful clinical consequences. Available data indicate that statins exert
      significant antithrombotic effects in clinical practice by reducing the
      occurrence of vascular atherothrombotic events, with a more prominent effect in
      high-risk patients. The mechanisms by which statins inhibit thrombosis have been
      extensively investigated, and several pathways appear to be involved. In
      particular, statins have been proposed to reduce platelet activation and to exert
      favorable effects on fibrinolysis, but no clear-cut conclusion can be drawn from
      available studies. Moreover, statins do not consistently influence fibrinogen or
      factor VII levels in plasma. In contrast, in vitro and in vivo data indicate that
      these compounds profoundly affect thrombin generation driven by tissue
      factor/factor VII pathway. In vitro studies indicate that this effect is not
      dependent on plasma cholesterol lowering but, rather, on the inhibition of
      isoprenoid biosynthesis. The relative contribution of reduced levels of
      prenylated proteins and of cholesterol pathway to the modulation of tissue factor
      expression is, however, hardly to be established in clinical settings.

PMID- 15861323
TI  - Anti-inflammatory properties of statins.
AB  - Increasing clinical and experimental evidence indicates that some beneficial
      effects of statins, known as efficient therapeutic agents in cardiovascular
      disease treatment, may result from their ability to modulate vascular and
      endothelial cell gene expression by mechanisms independent of cholesterol
      reduction. It has been shown that statins exhibit direct anti-inflammatory
      properties via inhibition of proinflammatory cytokine and chemokine secretion, as
      well as through adhesion molecule expression on leukocytes. Another important
      mechanism by which statins may modulate the immune response is inhibition of
      interferon gamma-induced expression of class II major histocompatibility
      complexes. Class II major histocompatibility complex expression is central to
      immune regulation in T cell-mediated autoimmune diseases, indicating a potential
      beneficial role of statins in these pathologies. Indeed, promising new
      preclinical data indicate that statins might be useful in the treatment of
      multiple sclerosis and rheumatoid arthritis.

PMID- 15861324
TI  - [Carotid stenosis in high risk patients. The SAPPHIRE study versus a decision
      analysis. Which is the best therapeutic option?].
AB  - INTRODUCTION: In the results from the SAPPHIRE study on high surgical risk
      patients with carotid stenosis there are no differences between carotid stent
      angioplasty (CSA) and carotid endarterectomy (CEA). AIMS: The aim of this study
      was to analyse the cost-effectiveness of these two interventions based on the
      data from the above-mentioned study and on our own experience in carotid surgery.
      PATIENTS AND METHODS: We evaluated 108 CSA carried out between 1999 and 2003. The
      morbidity and mortality rates in the subgroup of high risk patients, according to
      the criteria used in the SAPPHIRE study, were analysed according to whether they
      were symptomatic or asymptomatic. Data concerning endovascular treatment were
      taken from the literature. A cost-effectiveness study was conducted considering
      four possible perioperative events: absence of sequelae, AMI, established CVA and
      death. The computer software package DATAPro was used after fitting the decision
      to the theoretical quality of life for each of these groups. Cost-effectiveness
      was estimated based on the cost of each procedure. RESULTS: Of the 108 patients,
      41 (37.96%) belonged to the high risk subgroup; 46.3% of them were asymptomatic
      and 53.7% were symptomatic. In the 30 days following the intervention, one CVA
      (5.2%) and one AMI (4.5%) were observed. No deaths occurred. The decision
      analysis for symptomatic patients showed CEA to be the most effective therapeutic
      option. Similar results were obtained for asymptomatic patients. The average cost
      for CEA was 3,963 euros and rose to 5,158 euros in the case of CSA. CONCLUSIONS:
      In our study, CEA is the preferred technique in high risk patients owing to its
      having a better cost-benefit ratio.

PMID- 15861325
TI  - [Neonatal neurology decision-making starting from systematic reviews of Cochrane
      Collaboration].
AB  - INTRODUCTION: Cochrane Collaboration (CC) provides growing and readily accessible
      resource to help that decision-making care is based on detailed, critical, and
      current reviews of the best available evidence. There are many clinical questions
      for which there is no good evidence on which to base clinical practice. AIM: To
      analyse the bibliometric characteristics of the systematic reviews (SR) about
      neonatal neurology published in Neonatal CC. MATERIALS AND METHODS: Bibliometric
      analysis of The Cochrane Database Systematic Reviews in Neonatal CC, Issue 1,
      2004 (n = 169 SR). The dependent variable registered in each SR was subject area
      of study (mainly neurology subject area) and the rest of variables were
      considered independent: authors (number and country), dates (late review and
      update), characteristics of included clinical trials (number and type),
      characteristics of the newborns included (number and gestational age), reviewer's
      conclusions and potential conflicts of interest. RESULTS: Neurology was the third
      most important subject area in Neonatal CC (13 SR), after the subject area of
      respiratory (73 SR) and gastroenterology-nutrition (26 RS). We identified three
      selective clusters of secondary investigation in neonatal neurology SR:
      intraventricular haemorrhage (4 SR), perinatal asphyxia (4 SR) and opiate
      withdrawal syndrome (2 SR). The number of clinical trials (median 4), patients
      (median 193), update (46%), sufficient conclusion (54%) and potential conflicts
      of interest (8 %) in each SR is similar to the rest of SR in Neonatal CC; the
      only difference we found is less preterm infants (15%) in this SR. All the SR are
      about interventions for the treatment or prevention of diseases, and we don't
      found any review about diagnostic tests. CONCLUSIONS: At the moment, the neonatal
      neurology SR published in Neonatal CC are infrequent and almost half of them the
      reviewer's conclusions are insufficient for inferring probable effects in
      clinical practice. Many therapies in neonatal neurology persist without
      supportive evidence, and some common therapies may actually be harmful, and these
      are the conclusions found in SR about intraventricular haemorrhage. We detected
      no SR about important neuropediatric themes in neonatal period: hypoxic-ischemic
      encephalopathy, periventricular leukomalacia, neonatal seizures, hypotonia, etc.

PMID- 15861326
TI  - [Emotional consequences of providing care to amyotrophic lateral sclerosis
      patients].
AB  - INTRODUCTION AND AIMS: This study describes the emotional and personal
      consequences of providing care to amyotrophic lateral sclerosis (ALS) patients.
      SUBJECTS AND METHODS: Six caregivers aged from 23 to 67 years old (mean age: 38.2
      +/- 15.6), weight interviewed. The Hospital Anxiety and Depression Scale (HAS)
      and the OARS Activities of Daily Living Questionnaire were applied. The subjects
      were interviewed with semi-structured questions about medical information,
      caregiver burden, coping, social support, impact on his/her health, stressor and
      religious resources. In order to be included in the research, the subject had to
      be an ALS patient caregiver. Every interview was audio recorded and transcribed,
      and a content analysis was realized. RESULTS: They show emotions caused by
      unfavorable life conditions and were classified into seven main categories: 1)
      defenselessness, 2) negative affection, 3) hope, 4) sadness, 5) depression, 6)
      isolation and 7) loneliness. CONCLUSION: This study shows that providing care to
      ALS patient affects the familiar, social and emotional caregiver's system.

PMID- 15861327
TI  - [Neuropsychological study of 12 patients with pure degenerative cerebellar
      disease].
AB  - INTRODUCTION: The cerebellum has been traditionally associated with motor control
      learning and performance. However, since 1970 a growing body of clinical and
      experimental evidences has suggested that the cerebellum may be involved in
      nonmotor cognitive functions as well. OBJECTIVE: To explore the presence of
      eventual cognitive impairment in non-demented patients with isolated degenerative
      cerebellar diseases. PATIENTS AND METHODS: Twelve patients with the diagnosis of
      selective degenerative cerebellar disorders, either inherited or sporadic, were
      selected (mean age: 40.42 +/- 13.49 years; mean education level: 9.92 +/- 3.99
      years; duration of illness: 12.13 +/- 11.27 years, MMSE: 26.75 +/- 1.5) and
      evaluated through a standardized neuropsychological tests battery. Normalized Z
      scores were estimated and compared against 0, employing the t test for one
      sample. RESULTS: Significant cognitive deficits were found in the following
      domains: executive, visuo-spatial, memory and attention functions. Performance on
      the Wisconsin test showed a significative number of perseverative errors. Memory
      deficits included verbal learning and free recall difficulties, with good
      recognition of the material presented. CONCLUSIONS: The findings of this study
      are consistent with the role of the cerebellum as modulator of mental functions.
      The cognitive deficits resulting from cerebellar pathology may be related with
      the disruption of cerebello-cortical connexions involving a complex network which
      includes the prefrontal region, suggesting that the cerebellum may process
      cortical information coming from different areas linked with the control of
      cognition.

PMID- 15861328
TI  - [Kabuki make-up syndrome. A report of 18 Spanish cases].
AB  - AIM: To present 18 cases of Kabuki make-up syndrome with the associated
      morphological and neurological alterations. CASE REPORTS: The series consists of
      18 patients, 14 males and 4 females, who show the peculiar facial morphology of
      this disease. Ten cases were studied between 1968 and 1978, before the
      description of the syndrome. Most of these patients are now over 30 years and two
      perhaps surmounting the 40, if surviving. The other 8 cases were studied during
      the last 20 years (a few within the last 3 years). The studies of the patients
      were anamnesis with genetic history, EEG, image, cytogenetic, laboratory studies,
      and mental evaluation when the patients collaborated. The most important findings
      are the peculiar facial characteristics as well as the psychomotor and language
      retardation, the persistent fingertip pads and clinodactyly that were observed in
      all patients. Other studies, such as EEG, caryotype, biochemical investigation in
      blood, urine and CSF (in the studied cases), and the cerebral neuroradiological
      images (pneumoencephalography, CT or MR) disclosed normal results. None of the
      patients of this series were neurologically normal. Hyperactivity, respiratory
      infection and/or otitis were frequently observed. CONCLUSION: Kabuki make-up
      syndrome is a dysmorphologic and neurological disease of unknown origin. Its main
      manifestations involve facial appearance and brain function without anatomical
      anomalies. None of the patients was sent to the Pediatric Neurology service with
      the suspicion of Kabuki make-up syndrome.

PMID- 15861329
TI  - [The identification of multiple thrombophilic risk factors in an infant with
      cerebrovascular accident].
AB  - INTRODUCTION: Neonatal stroke (NNS) incidence appears to be increasing over the
      last years. This is believed to be a consequence of diagnostic accuracy rather
      than a real amplification of this entity. Nowadays, NNS incidence is estimated to
      be 1:4000 full newborns. CASE REPORT: Child with left middle cerebral artery
      territory infarction in which several thromboembolic risk factors were documented
      both in the child (neonatal sepsis and factor V Leiden) and his mother (lupus
      anticoagulant, pre-eclampsy and factor V Leiden). CONCLUSIONS: This case supports
      the increasing evidence in recent reports that association of multiple
      prothrombotic risk factors (maternal and foetal) is present in NNS genesis. This
      way the authors agree that wide prothrombotic study may be of crucial interest in
      identifying subjacent thrombophilic disease, even when an exogenous risk factor
      is present.

PMID- 15861330
TI  - [Retinopathy secondary to treatment with Interferon beta-1a in a patient with
      multiple sclerosis].
AB  - INTRODUCTION: Although visual symptoms of multiple sclerosis (MS) are very
      frequent, they are rarely related with treatment with interferon. This is the
      first case reported in the literature of retinopathy associated with subcutaneous
      interferon beta-1a, and the second related to interferons in MS. CASE REPORT: A
      30-year-old female diagnosed with relapsing-remitting MS who, at 3 months after
      starting treatment with subcutaneous interferon beta-1a (44 microg/3 times a
      week), displayed visual disorders. Retinal lesions in the form of cotton wool
      spots were found as symptoms of microinfarctions in the retina. The lesions got
      better after stopping treatment and the patient was found to be asymptomatic.
      CONCLUSIONS: The existence of retinopathy secondary to interferon has been known
      in the treatment of hepatitis C and neoplasias with interferon alfa since 1990.
      Despite being a frequently occurring complication, it is usually a mild condition
      and disappears on withdrawing treatment, or even if it is continued. It is
      attributed to deposits of immunocomplexes and complement activation in the blood
      vessels of the retina. Only one other case associated to treatment of MS with
      interferon beta has been reported in the literature, more specifically related to
      subcutaneous interferon beta-1b. The clinical characteristics of both cases are
      identical to those associated to interferon alfa. Despite the fact that the
      frequency of appearance seems to be lower than in the case of interferon alfa,
      the physician must bear in mind the possibility encountering this complication.

PMID- 15861331
TI  - [Advances in sleep disorders].
AB  - OBJECTIVE: This review aims to offer a panoramic overview of the most common
      sleep disorders, the methodology of the study, their clinical and
      physiopathological aspects and their treatment. DEVELOPMENT: First, we give a
      brief overview of the methodology of the study of sleep/wakefulness with
      examinations which are considered essential today. Next, and following the
      International Classification, we describe sleep disorders which require the
      knowledge of a physician specialized in sleep pathology: insomnia, hypersomnia,
      circadian rhythm disorders and parasomnias. We also describe conditions related
      to sleep or worsened during sleep (snoring, apneas, cardiovascular disorders,
      etc.), the study of which requires the collaboration of a large number of
      specialists. CONCLUSION: The study of sleep and wakefulness disorders is clearly
      a branch of medicine due to the high prevalence of these disorders in the general
      population, their morbidity and their negative consequences in social and working
      life, especially as a cause of road and workplace accidents.

PMID- 15861332
TI  - [Inflammatory response in spontaneous intracerebral haemorrhage].
AB  - INTRODUCTION: At date, there is increasing evidence that inflammatory processes
      are involved in cerebrovascular events. Trauma and ischemic injury are
      characterized by acute local inflammation and changes in levels of inflammatory
      cytokines in body fluids of human patients. However, very few studies have been
      directed to establish the role and the relationship between inflammation and
      hemorrhagic stroke. DEVELOPMENT: After intracerebral hemorrhage, inflammatory
      mediators from the blood might enter to the brain and induce an inflammatory
      reaction, although the brain cells itself are capable of producing many of these
      agents. Whatever, this markers of inflammation contributes to the development of
      a systemic response. High levels of C reactive protein (CRP), an acute and
      sensitive phase protein to inflammatory reactions, are present among individuals
      at risk for future cerebro or cardiovascular event. Elevated CRP also predicts
      the outcome. CONCLUSION: We present the little evidence about the relationship
      between inflammation and hemorrhagic stroke.

PMID- 15861334
TI  - [Reply. Multiple sclerosis and neurocysticercosis].

PMID- 15861335
TI  - [Neck-tongue syndrome].

PMID- 15861337
TI  - Quiz page. Acute infarction in a grafted kidney.

PMID- 15861339
TI  - Mycobacterium simiae: a previously undescribed pathogen in peritoneal dialysis
      peritonitis.
AB  - Peritonitis is a major complication of peritoneal dialysis (PD). Coagulase
      negative staphylococcus, Staphylococcus aureus , and Gram-negative bacteria cause
      the majority of these infections and usually are amenable to conventional
      antibiotic therapy, allowing continuation of PD. Mycobacterial and fungal
      peritonitis represent a more difficult clinical challenge. The infecting organism
      is often difficult to isolate and can rarely be eradicated without catheter
      removal. Immunocompromised patients are susceptible to opportunistic infection
      and, in the context of PD, may have PD peritonitis with different organisms from
      immunocompetent patients. Here the authors report for the first time PD
      peritonitis caused by Mycobacterium simiae , a nontuberculous mycobacterium, in a
      human immunodeficiency virus-positive patient. In addition the difficulty in
      diagnosing and managing nontuberculous PD peritonitis is discussed.

PMID- 15861340
TI  - Type III cryoglobulinemia complicated by renal cortical necrosis.
AB  - Renal involvement is rare in patients with type III cryoglobulinemia. We report a
      case of renal cortical necrosis in a patient with type III cryoglobulinemia.
      Renal function improved partially after treatment with plasma exchange, steroids,
      and cyclophosphamide. Renal magnetic resonance imaging was a valuable tool in the
      evaluation of the extent of renal cortical necrosis and improvement in renal
      vascularization after treatment.

PMID- 15861341
TI  - Chronic renal failure and proteinuria in adulthood: Fabry disease predominantly
      affecting the kidneys.
AB  - The prognosis of Fabry disease has changed since enzyme-replacement treatment was
      introduced. Therefore, early diagnosis is instrumental. We describe a family
      presenting with chronic renal failure and proteinuria in which classic skin and
      neurological features were absent and the diagnosis of Fabry disease was
      difficult and not established until a second family member developed renal
      abnormalities. A 35-year-old man was admitted because he was overweight and had
      hypertension, with a serum creatinine level of 1.3 mg/dL (115 micromol/L) and
      protein excretion of 870 mg/d. Because 1 brother, who died years ago at the age
      of 32 years of acute myeloid leukemia, also had chronic renal failure and
      proteinuria, the diagnosis of Fabry disease was entertained. In the index
      patient, acroparesthesia, hypohidrosis, pain, angiokeratomas of the skin, and
      cornea verticillata suggesting Fabry disease were absent. Conversely, renal
      biopsy showed typical globotriaosylceramide deposits, and leukocyte alpha
      galactosidase (alpha-GLA) A activity was decreased. Analysis of the alpha-GLA
      gene showed the mutation E66K. The mutation also was found in another
      asymptomatic 30-year-old brother who also had chronic renal failure and
      proteinuria, but normal extrarenal findings. In the brother who died, Fabry
      disease, missed at autopsy because of cancer-related findings, could be confirmed
      after repeated review of histological slides. Mutation carriers also included the
      mother, a sister (both without abnormalities), and a nephew (with episodic pains
      in his feet). We conclude that familial chronic renal failure combined with
      proteinuria is suggestive of Fabry disease, and such specific mutations as E66K
      predominantly may affect the kidneys.

PMID- 15861342
TI  - Hypercalcemia in a patient with common variable immunodeficiency and renal
      granulomas.
AB  - Common variable immunodeficiency (CVID) is the most common primary
      immunodeficiency. A granulomatous form of the condition is recognized. Renal
      involvement is rare. The authors present the first case of CVID with biopsy
      proven noncaseating renal granulomas, in association with hypercalcemia. The
      mechanism of hypercalcemia in granulomatous disorders, and the difficulty of
      differentiating granulomatous CVID from sarcoidosis, are discussed.

PMID- 15861343
TI  - Daily hemodialysis: the time has come?--Pro.

PMID- 15861344
TI  - Daily hemodialysis: the time has come?--Con.

PMID- 15861345
TI  - Antiviral drug-induced nephrotoxicity.
AB  - Drug-induced kidney injury is a major side effect in clinical practice,
      frequently leading to acute renal failure (ARF). It accounts for more than 2% to
      15% of cases of ARF in patients admitted to the hospital or in the intensive care
      unit, respectively. The exact frequency of nephrotoxicity induced by antiviral
      drugs is difficult to determine. Antiviral drugs cause renal failure through a
      variety of mechanisms. Direct renal tubular toxicity has been described with a
      number of new medications with unique effects on epithelial cells of the kidney.
      These include cidofovir, adefovir dipivoxil, and tenofovir, as well as acyclovir.
      Additionally, crystal deposition in the kidney may promote the development of
      renal failure. Several different drugs have been described to induce crystal
      nephropathy, including acyclovir and the protease inhibitor indinavir. Renal
      injury associated with antiviral drugs involves diverse processes having effects
      on the renal transporters, as well as on tubule cells. In this article, we review
      the pathogenesis of antiviral drug-induced kidney injury, common nephrotoxic
      renal syndromes, and strategies for preventing kidney injury.

PMID- 15861346
TI  - Increased endothelin 1 expression in adult-onset minimal change nephropathy with
      acute renal failure.
AB  - BACKGROUND: Acute renal failure (ARF) occurs in some adult patients with minimal
      change nephropathy (MCN). To investigate clinical and pathological factors
      associated with developing ARF, we compared clinical features and kidney
      pathological characteristics of endothelin 1 (ET-1) expression in patients with
      adult-onset MCN with and without ARF. METHODS: The patient population consisted
      of 53 patients consecutively diagnosed with adult-onset MCN during a 10-year
      period. Based on creatinine clearance, 25 patients were assigned to the ARF group
      and 28 patients were assigned to the non-ARF group. RESULTS: Clinical data show
      that the ARF group had a higher blood pressure, higher serum cholesterol level,
      and lower serum albumin level than the non-ARF group. Pathological data showed
      more severe foot-process effacement, interstitial edema, and flattened tubular
      epithelium in the same group. Greater ET-1 expression was detected in vessels,
      tubules, and glomeruli of the ARF compared with non-ARF group. The ARF group
      experienced a lower steroid response rate. However, there was no significant
      difference in stability of remission to steroid treatment in patients who
      achieved a remission. CONCLUSION: ARF associated with enhanced kidney ET-1
      expression is a reversible complication of MCN that occurs frequently in patients
      with apparently expanded extracellular fluid. Presumptively, ARF may develop as
      an amplification of the underlying pathogenesis of MCN involved in enhanced ET-1
      expression, which may be superimposed by a transient episode of circulatory
      insufficiency during diuretic treatment.

PMID- 15861347
TI  - Acute renal failure after cardiac surgery for carcinoid heart disease: incidence,
      risk factors, and prognosis.
AB  - BACKGROUND: Cardiac surgery for carcinoid heart disease may be associated with
      acute renal failure (ARF) and multiorgan dysfunction postoperatively. This study
      was performed to determine the incidence, risk factors, and prognosis of ARF
      after cardiac surgery for carcinoid heart disease. METHODS: This is a case
      control study of 86 consecutive patients who underwent cardiac surgery for
      carcinoid heart disease. ARF is defined as hemodialysis requirement or serum
      creatinine level 50% greater than baseline, resulting in an estimated creatinine
      clearance less than 40 mL/min (0.67 mL/s). Preoperative, operative, and
      postoperative characteristics were examined and compared between groups to
      determine risk factors and prognosis of ARF. RESULTS: ARF occurred in 22% of
      cases (19 of 86 patients). Preoperative characteristics and type of procedure did
      not differ between groups. Operative variables associated with ARF by means of
      univariate analysis included longer surgical and bypass times, intra-aortic
      balloon pump use, and perioperative epinephrine requirement. Postoperatively, ARF
      was associated with epinephrine use, prolonged mechanical ventilation, prolonged
      intensive care unit admission, and higher Acute Physiology and Chronic Health
      Evaluation II scores. Perioperative mortality in the ARF group was 47% versus
      4.5% in the control group (odds ratio, 36.1; 95% confidence interval, 8.0 to
      261.8). CONCLUSION: ARF developed in a relatively high proportion of this cohort,
      but traditional preoperative risks failed to predict post-cardiac surgery ARF.
      Variables closely related to perioperative hemodynamic compromise were associated
      with ARF. ARF portends a particularly poor prognosis in this cohort that is
      explained largely by multiorgan failure syndrome.

PMID- 15861348
TI  - A dipstick protein and specific gravity algorithm accurately predicts
      pathological proteinuria.
AB  - BACKGROUND: The proper strategy to screen for early chronic kidney disease is
      debatable, but protein-creatinine ratio from a random urine sample (UPC) commonly
      is used. The purpose is to determine whether dipstick data effectively identify
      patients with increased UPC ratios. Because urine concentration affects
      proteinuria interpretation, we hypothesized that dipstick protein (DSP) and
      specific gravity (SG) are sufficient for screening. METHODS: A hospital
      laboratory database was searched for urine samples simultaneously assayed for UPC
      ratio, DSP, and SG (n = 2,098). A random 70% of the cohort was used to generate a
      development model, which was validated in the remaining 30%. Samples were
      stratified according to DSP and SG values. A DSP versus SG matrix was created,
      and each sample was allocated to a discrete DSP-SG category. Proportions of
      samples with overt (UPC ratio > or = 500 mg/g) and nephrotic-range proteinuria
      (UPC ratio > or = 3,000 mg/g) were calculated for all 40 cells. RESULTS: Optimum
      correlations between DSP-SG cells and UPC ratios were determined for the
      development model, yielding 97.0% negative predictive value (NPV) for a UPC ratio
      of 500 mg/g or less and 97.5% positive predictive value (PPV) for a UPC ratio of
      500 mg/g or greater. NPV for a UPC ratio of 3,000 mg/g or less was 99.7%.
      Application of the model to the validation sample showed a 96.5% NPV for a UPC
      ratio of 500 mg/g or less, 99.4% PPV for a UPC ratio of 500 mg/g or greater, and
      99.0% NPV for a UPC ratio of 3,000 mg/g or less. CONCLUSION: DSP and SG values
      effectively identify patients requiring proteinuria quantification by means of
      UPC ratio. A Web-based tool was developed that allows DSP and SG value entry and
      provides a recommendation regarding the need for proteinuria quantification.

PMID- 15861349
TI  - Renal duplex parameters, blood pressure, and renal function in elderly people.
AB  - BACKGROUND: Changes in renal artery and renal parenchyma perfusion are believed
      to correlate with severity of hypertension and worsened renal function, but
      population-based studies of these associations are not available. This study
      examines relationships between parameters derived from renal duplex sonography
      (RDS), blood pressure (BP), and excretory renal function in a population-based
      cohort of elderly Americans. METHODS: Through an ancillary study to the
      Cardiovascular Health Study, 758 participants (37% men; mean age, 77 years)
      underwent RDS in which flow velocities and frequency shifts were determined from
      spectral analysis of Doppler-shifted signals obtained from the renal artery and
      parenchyma. Associations of these duplex parameters with BP and inverse serum
      creatinine were examined by using multivariate regression techniques. RESULTS:
      Main renal artery peak systolic flow velocity (PSV) showed independent
      associations with BP, with an SD increase in PSV (0.53 m/s) associated with a 3.3
      mm Hg increase in systolic BP (SBP) and a 2.4-mm Hg decrease in diastolic BP
      (DBP). An SD decrease in end-diastolic frequency shift (EDF; 131 kHz) was
      associated with a 6.0-mm Hg increase in SBP, a 4.2-mm Hg decrease in DBP, and a
      significant 3.7% decrease in inverse serum creatinine. CONCLUSION: Increases in
      renal artery PSV and decreases in parenchymal EDF are associated with increased
      SBP and decreased DBP. Moreover, decreased parenchymal EDF showed significant
      associations with impaired excretory renal function. These results suggest that
      renal duplex parameters are associated with renal parenchymal changes caused by
      hypertension and progressive renal dysfunction in elderly people.

PMID- 15861350
TI  - Disturbances of phosphate metabolism: another feature of metabolic syndrome.
AB  - BACKGROUND: Despite important recent advances in the understanding of the
      consequences of metabolic syndrome, its pathophysiological characteristics remain
      unclear. It has been proposed that disturbances in phosphate metabolism may
      contribute to the development of this constellation of cardiovascular risk
      factors. However, there have been insufficient clinical data supporting this
      hypothesis to date. The aim of our study is to confirm the presence of
      hypophosphatemia in patients with metabolic syndrome, as well as investigate
      mechanisms that may underlie the disturbances in phosphate metabolism in this
      patient group. METHODS: Two hundred fifty-five individuals were enrolled. The
      diagnosis of metabolic syndrome was based on Adult Treatment Panel III
      guidelines. Subjects with fewer than 3 criteria served as controls. RESULTS:
      Patients with metabolic syndrome showed significantly lower phosphate and
      magnesium levels compared with controls. Because fractional excretion of
      phosphate was similar in both groups, we assume that hypophosphatemia in patients
      with metabolic syndrome can be attributed to decreased dietary intake, as well as
      internal redistribution of this element. Lower magnesium values in the patient
      group may result from the same mechanisms as lower phosphate levels. In addition,
      hyperinsulinemia-induced renal magnesium wasting also may be a contributory
      factor. CONCLUSION: Patients with metabolic syndrome show significantly lower
      phosphate and magnesium levels compared with healthy individuals. The clinical
      significance of these disturbances, as well as their importance as targets for
      preventive or therapeutic interventions, remains to be established.

PMID- 15861351
TI  - Cross-sectional association of serum phosphate with carotid intima-medial
      thickness in hemodialysis patients.
AB  - BACKGROUND: Although an increased serum phosphate concentration is a significant
      risk factor for vascular calcification, it is unclear whether serum phosphate
      level is a risk factor for increased arterial wall thickness in hemodialysis
      patients. METHODS: Using B-mode ultrasonography, we examined intima-medial
      thickness (IMT) of the carotid artery of hemodialysis patients and analyzed risk
      factors for increased IMT with regard to the effect of serum phosphate. Seven
      hundred sixteen hemodialysis patients were enrolled (547 patients without
      diabetes, 169 patients with diabetes; 441 men, 275 women; age, 60 +/- 8.5 years).
      RESULTS: IMT of patients with diabetes was significantly greater than that of
      patients without diabetes (0.859 +/- 0.250 versus 0.783 +/- 0.178 mm; P <
      0.0001). For the group of all patients, IMT correlated weakly, but significantly,
      with serum phosphate level (r = 0.093; P = 0.0127). In multiple regression
      analysis of the group of all patients, greater serum phosphate level (beta =
      0.166; P < 0.0001) was shown to be a significant independent risk factor for
      increased carotid IMT, in addition to other significant independent risk factors,
      including advanced age, higher blood pressure, greater non-high-density
      lipoprotein cholesterol level, and the presence of diabetes (R2 = 0.1119; P <
      0.00001). In multiple regression analyses performed separately for hemodialysis
      patients without and with diabetes, greater phosphate level and advanced age were
      significant independent risk factors for increased IMT, independent of other
      confounding risk factors. CONCLUSION: These results show that in addition to
      advanced age, greater serum phosphate level is a significant and independent
      factor associated with advanced arteriosclerosis in hemodialysis patients with
      and without diabetes, suggesting that phosphate levels should be controlled
      appropriately to prevent an increase in arterial wall thickness in hemodialysis
      patients.

PMID- 15861353
TI  - Sleep apnea, coronary artery disease, and antioxidant status in hemodialysis
      patients.
AB  - BACKGROUND: It recently was suggested that sleep apnea syndrome (SAS) is
      associated with the cardiovascular complications and outcomes seen in patients
      with end-stage renal disease (ESRD). This study investigates the association of
      SAS with coronary artery disease and antioxidant status in patients with ESRD.
      METHODS: Twenty-six hemodialysis patients underwent overnight polysomnography to
      evaluate sleep parameters. We performed multirow spiral computed tomography to
      derive coronary artery calcification (CAC) scores as an indicator of the severity
      of coronary artery disease and measured predialysis serum total antioxidant
      status (TAS) as a marker of antioxidant defenses. RESULTS: Nine of 26 patients
      had normal to mild SAS with an apnea-hypopnea index (AHI) less than 15, 9
      patients had moderate SAS with an AHI of 15 to 30, and the remaining 8 patients
      had severe SAS with an AHI greater than 30. AHI and oxygen desaturation index
      (ODI) were strongly interrelated (r = 0.754; P < 0.001). CAC severity was
      associated with SAS severity: median CAC scores increased (P = 0.009) with
      increasing AHI category. However, values for TAS were not significantly different
      among the 3 AHI categories. CAC score also correlated positively (r = 0.564; P =
      0.003) with ODI, and TAS correlated negatively (r = -0.539; P = 0.005) with ODI.
      CONCLUSION: These results suggest that frequent oxygen desaturation triggered by
      SAS is associated with severe coronary artery disease and decreased antioxidant
      status in patients with ESRD. However, conclusions from this study should be
      drawn with caution because of its methodological limitations (cross-sectional
      design, heterogeneity of study population, and small number of patients).

PMID- 15861352
TI  - Low doses of losartan and trandolapril improve arterial stiffness in hemodialysis
      patients.
AB  - BACKGROUND: Hemodialysis patients have uremic dyslipidemia, represented by
      elevated serum intermediate-density lipoprotein cholesterol (IDL-C) levels, and
      an increased cardiovascular mortality rate. This study was performed to determine
      the low-dose effects of the angiotensin II receptor blocker losartan and the
      angiotensin-converting enzyme inhibitor trandolapril on pulse wave velocity
      (PWV), which predicts cardiovascular morbidity and mortality in hemodialysis
      patients. METHODS: Serum lipid levels and PWV were monitored for 12 months in 64
      hemodialysis patients who were administered low doses of losartan or trandolapril
      or a placebo. RESULTS: At the start of the study, there were no differences in
      patient characteristics among the 3 groups. PWV tended to increase in the placebo
      group during the 12-month study period, but decreased significantly in the
      losartan and trandolapril groups, and decreases in PWV were similar in the
      losartan and trandolapril groups. There were no changes in blood pressure,
      hematocrit, erythropoietin dose, ankle-brachial index, serum lipid levels, serum
      8-isoprostane levels, or serum C-reactive protein levels during the 12-month
      study period, but there was an increase in serum triglyceride levels in the
      losartan group and a decrease in serum IDL-C levels in the losartan and
      trandolapril groups. CONCLUSION: In hemodialysis patients, trandolapril is as
      effective as losartan in decreasing PWV independent of its depressor effect and
      in suppressing elevated IDL-C levels. Long-term blockade of the renin-angiotensin
      system may have a beneficial effect on the acceleration of atherosclerosis and
      uremic dyslipidemia.

PMID- 15861354
TI  - Urea clearance in dysfunctional catheters is improved by reversing the line
      position despite increased access recirculation.
AB  - BACKGROUND: Problematic or dysfunctional hemodialysis (HD) catheters are
      routinely reversed to achieve adequate blood flow for dialysis delivery. The
      purpose of the study is to determine the effect of varying blood pump speed (Qb)
      on access recirculation (AR), and urea clearance (K) in dysfunctional catheters
      in the normal and reversed positions. METHODS: Nineteen HD patients with tunneled
      cuffed catheters (5 functional and 14 dysfunctional catheters) were included;
      dysfunctional catheters are defined as the inability to attain a Qb of 300 mL/min
      or greater on 2 consecutive HD runs. AR and K measurements were obtained
      systematically for each catheter in the normal and reversed positions at
      increasing Qbs. K was measured using the ionic dialysance technique. RESULTS: In
      functional catheters, AR in the normal position was 0% and increased to 15% +/-
      13% when reversed. Dysfunctional catheters had a greater AR of 25% +/- 16% when
      reversed. In functional catheters, there was no evidence of an increase in AR
      with increasing Qb irrespective of position. Similarly, there was no relationship
      between increasing AR and greater Qbs (r 2 = 0.10) in dysfunctional catheters. In
      dysfunctional catheters, when reversed, mean K increased from 128 +/- 10 mL/min
      at a Qb of 200 mL/min to 157 +/- 38 mL/min at maximal Qb (P < 0.05). CONCLUSION:
      We show that at increasing Qbs, K is improved in both functional and
      dysfunctional catheters. Data from the study are used to describe a nomogram to
      determine minimum Qb for a dysfunctional catheter in reversed position to
      maximize K.

PMID- 15861355
TI  - Strong association between volume status and nutritional status in peritoneal
      dialysis patients.
AB  - BACKGROUND: Malnutrition is a strong predictor of mortality in maintenance
      peritoneal dialysis (PD) patients. Various factors have been identified to
      contribute to the development of malnutrition. The present study tried to
      investigate the possible role of fluid overload in the development of
      malnutrition. METHODS: Twenty-eight PD patients were included in this study.
      Fluid status was evaluated by means of repeated bioimpedance analysis, and
      nutritional status was assessed by means of handgrip strength and subjective
      global assessment. All patients were followed up closely for 9 months. Based on
      changes in bioimpedance analysis data, patients were divided into group A (with
      continuous and steadily improved fluid status; n = 18) and group B (with
      consistent fluid overload; n = 10). RESULTS: There were no differences in sex,
      age, and height between the 2 groups. In group A, patients' extracellular water
      (ECW) volume decreased significantly during follow-up, whereas intracellular
      water (ICW) volume increased significantly (both P < 0.001). In group B, ECW
      volume increased significantly, whereas ICW volume increased at an early stage
      and then decreased. The ratio of ECW to total-body water decreased significantly
      in group A, but increased significantly in group B. Along with the improvement in
      fluid status, nutritional status in group A also improved significantly (the
      prevalence of malnutrition decreased from 66.7% to 11.1%; P < 0.01). However, in
      group B, nutritional status deteriorated significantly (handgrip strength
      decreased from 238.33 +/- 88.93 to 216.1 +/- 86.19 N; P < 0.05; and the
      prevalence of malnutrition increased from 40% to 50%). CONCLUSION: Our data
      suggest there is a strong association between fluid status and nutritional
      status. Improved fluid status is associated with improvement in nutritional
      status, whereas deterioration in fluid status is associated with the development
      of malnutrition.

PMID- 15861356
TI  - The long-term prognosis of renal transplantation in patients with lupus
      nephritis.
AB  - BACKGROUND: Few data are available about the long-term outcome of renal
      transplantation in patients with systemic lupus erythematosus (SLE). METHODS:
      Between June 1982 and 2004, a total of 33 adults with lupus nephritis received 35
      kidney allografts. Outcomes of these grafts and those of 70 controls matched for
      age, sex, and donor source who underwent transplantation during the same period
      were compared. RESULTS: Mean follow-up after renal transplantation was 91 +/- 59
      months for patients with lupus and 90 +/- 64 months for controls. Actuarial 15
      year patient (80% versus 83%) and death-censored graft survival rates (69% versus
      67%) were not significantly different between patients with lupus and controls.
      Risks for acute and chronic rejection, arterial hypertension, and infection were
      not different between the 2 groups. Mean serum creatinine levels also were
      similar in the 2 groups at the last follow-up visit. Intravascular thrombotic
      events occurred in 9 patients with SLE (26%) and 6 controls (8.6%; P = 0.038). In
      the SLE group, 6 of 7 antiphospholipid (aPL) antibody-positive versus 3 of 17 aPL
      antibody-negative patients experienced thrombotic events ( P = 0.015). Recurrence
      of lupus nephritis was documented in 3 renal grafts (8.6%), but no graft was lost
      because of recurrent lupus nephritis. CONCLUSION: Long-term patient and graft
      survival probabilities were similar in patients with SLE and matched controls.
      The risk for thrombotic complications was greater in patients with SLE,
      particularly aPL-positive patients. Nephritis recurred in less than 10% of
      patients with SLE and did not influence graft survival.

PMID- 15861357
TI  - A rationale for intradialytic exercise training as standard clinical practice in
      ESRD.
AB  - The purpose of this article is to present a rationale for intradialytic exercise
      training in patients with end-stage renal disease based on the empirical evidence
      to date and determine whether this evidence has translated into enhanced renal
      rehabilitation practices throughout the world. According to the published
      literature, intradialytic exercise improves exercise adoption and adherence in
      this cohort, is performed safely, and is feasible to administer. Moreover,
      intradialytic exercise can improve solute removal, dialysis adequacy,
      intradialytic protein synthesis, muscular strength, peak oxygen consumption,
      nutritional status, and quality of life. Despite these findings, there currently
      are no policies or position stands regarding exercise prescription for
      hemodialysis patients in Australia. According to a telephone survey we conducted,
      intradialytic exercise programs are essentially nonexistent in this country.
      However, such programs are being implemented successfully as standard clinical
      practice in dialysis units in Germany, and there is reason to believe that this
      practice can be expanded throughout the world. At present, additional research is
      indicated. There is a lack of large-scale, robustly designed, randomized,
      controlled trials of intradialytic exercise training. Such research is needed to
      conclusively show the clinical importance of intradialytic exercise for
      hemodialysis patients, which may influence current standard clinical practice
      among nephrologists and, as such, improve the health and quality of life of this
      vulnerable cohort.

PMID- 15861358
TI  - Analyzing the true cost of delivering medications.
AB  - Reimbursement to providers for delivering medications in the dialysis field is a
      subject of current concern, with some payors limiting payment to an amount
      equaling the provider's acquisition cost. At the same time, some providers
      arbitrarily mark up medications by a large factor. For dialysis, as well as for
      the general medical field, an objective approach is required for both providers
      and payors to fairly set prices and reimbursement levels. This analysis evaluated
      all cost elements involved in the delivery of medications and determined that an
      increase over the acquisition cost is appropriate for pricing and reimbursement.
      The increase has 2 parts: a fixed cost associated with resources required for a
      medication irrespective of its cost and a markup on the acquisition price. The
      conclusion of this analysis is that an increase over acquisition cost in
      reimbursement of providers for delivering medications is required to fairly
      compensate them for their actual costs and avoid compelling them to either incur
      a loss or cost shift by overcharging some payors to compensate for underpayment
      by others. Planned adjustments in Medicare reimbursement for dialysis may not
      recognize this reality.

PMID- 15861359
TI  - Tularemia in a kidney transplant recipient: an unsuspected case and literature
      review.
AB  - Tularemia is a zoonotic infection that has rarely been reported in transplant
      recipients. The authors present a case of unsuspected tularemia in a kidney
      transplant patient that was diagnosed by isolation of Francisella tularensis in
      the blood. The patient was treated successfully with antibiotics. During
      diagnostic workup, a laboratory technician was exposed to tularemia by inhalation
      of the culture plate and received postexposure prophylaxis. This report
      emphasizes the importance of exposure history in the investigation of fever in an
      immunocompromised host and the special precautions needed when a virulent
      infectious organism is suspected.

PMID- 15861360
TI  - Late recurrence of scleroderma renal crisis in a renal transplant recipient
      despite angiotensin II blockade.
AB  - Scleroderma renal crisis is the most severe renal manifestation of scleroderma
      and has been reported to recur rarely early after renal transplantation.
      Angiotensin II blockade is critical in preventing and treating scleroderma renal
      crisis, but some concern exists as to whether angiotensin II receptor blockers
      are clinically equivalent to angiotensin-converting enzyme inhibitors. The
      current case indicates that late recurrences of scleroderma renal crisis are
      possible in renal transplant recipients and that angiotensin-converting enzyme
      inhibitors, rather than angiotensin II receptor blockers, may be the superior
      drugs for such patients.

PMID- 15861362
TI  - Disorders of potassium and acid-base balance.

PMID- 15861361
TI  - Can focusing on self-care reduce disparities in kidney transplantation outcomes?

PMID- 15861363
TI  - SLE and rapidly progressive glomerulonephritis.

PMID- 15861364
TI  - A rare cause of necrotizing and crescentic glomerulonephritis in a young adult
      male.

PMID- 15861366
TI  - Overestimation of urinary peptide excretion.

PMID- 15861368
TI  - Living donor list exchanges disadvantage blood-group--O recipients.

PMID- 15861369
TI  - Coronary artery calcification in nondialyzed patients with chronic kidney
      diseases.

PMID- 15861371
TI  - The importance of molecular vibrations: the sign change of the optical rotation
      of methyloxirane.

PMID- 15861370
TI  - Effect of nitric oxide on the development of nitrofen-induced fetal hypoplastic
      lung explants.
AB  - BACKGROUND/PURPOSE: Nitric oxide (NO) is an important cell-signaling molecule,
      and its generators, nitric oxide synthases, are expressed temporospatially in
      fetal rat lung. Recently, NO has been reported to modulate branching of the fetal
      rat lung lobe in vitro. We designed this study to evaluate the effect of NO on
      the morphogenesis of hypoplastic lung using nitrofen-induced rat lung explant
      model. METHODS: A hypoplastic fetal lung model and a normal control lung model
      were induced by feeding a pregnant rat with nitrofen (100 mg) or olive oil on day
      9.5 of gestation, respectively. Fetal lungs were harvested on day 13.5 and placed
      in organ culture containing serum-free medium Dulbecco modified Eagle medium. An
      NO donor, DETA NONOate (DETA/NO), was added daily in the culture medium. The lung
      cultures were divided into 4 groups: group 1 (n = 8), normal controls without
      DETA/NO; group 2 (n = 22), normal controls with DETA/NO; group 3 (n = 13),
      hypoplastic lungs without DETA/NO; group 4 (n = 22), hypoplastic lungs with
      DETA/NO. The fetal lungs were incubated for 48 hours at 37 degrees C with 5% CO2.
      Lung bud count and area of the specimens were measured under computer-assisted
      digital tracings. The rate of increase in bud count and lung area was calculated
      as the ratio of each value at 48 hours minus each value at 0 hour, divided by the
      value at 0 hour. RESULTS: The lung bud count was significantly increased in group
      2 compared with group 1 at a concentration of 50 micromol/L DETA/NO (P < .05). In
      the nitrofen group, the lung bud count was significantly increased in group 4
      compared with group 3 at 100 micromol/L DETA/NO added (P < .05). There was no
      significant difference in the rate of increase in whole lung area among the 4
      groups. The peak increase rates of lung area and bud count were significantly
      lower in group 4 compared with group 2. CONCLUSIONS: This study demonstrates that
      the NO donor, DETA/NO, promotes branching of the nitrofen-induced hypoplastic
      fetal lung explant. These data suggest that NO may modulate the development of
      the nitrofen-induced hypoplastic lung.

PMID- 15861372
TI  - Affinity interactions between phenylboronic acid-carrying self-assembled
      monolayers and flavin adenine dinucleotide or horseradish peroxidase.
AB  - A method is provided for the recognition of glycated molecules based on their
      binding affinities to boronate-carrying monolayers. The affinity interaction of
      flavin adenine dinucleotide (FAD) and horseradish peroxidase (HRP) with
      phenylboronic acid monolayers on gold was investigated by using voltammetric and
      microgravimetric methods. Conjugates of 3-aminophenylboronic acid and 3,3'
      dithiodipropionic acid di(N-hydroxysuccinimide ester) or 11-mercaptoundecanoic
      acid were prepared and self-assembled on gold surfaces to generate monolayers.
      FAD is bound to this modified surface and recognized by a pair of redox peaks
      with a formal potential of -0.433 V in a 0.1 M phosphate buffer solution, pH 6.5.
      Upon addition of a sugar to the buffer, the bound FAD could be replaced,
      indicating that the binding is reversible. Voltammetric, mass measurements, and
      photometric activity assays show that the HRP can also be bound to the interface.
      This binding is reversible, and HRP can be replaced by sorbitol or removed in
      acidic solution. The effects of pH, incubation time, and concentration of
      H(2)O(2) were studied by comparing the catalytic reduction of H(2)O(2) in the
      presence of the electron-donor thionine. The catalytic current of the HRP-loaded
      electrode was proportional to HRP concentrations in the incubation solution in
      the range between 5 microg mL(-1) and 0.1 mg mL(-1) with a linear slope of 3.34
      microA mL mg(-1) and a correlation coefficient of 0.9945.

PMID- 15861373
TI  - Two-photon absorption properties of 2,6-bis(styryl)anthracene derivatives:
      effects of donor-acceptor substituents and the pi center.
AB  - A series of 2,6- and 2,7-bis(styryl)anthracene derivatives with the donors at the
      styryl group and acceptors at the 9,10-positions have been synthesized, and their
      two-photon cross sections (Phidelta(max)) were determined. These compounds
      exhibit a peak two-photon absorptivity (delta(max)) in the range of 700-2500 GM
      at 780-1030 nm. Values of lambda(max) and Stokes shifts increase as the acceptor
      is changed to a stronger one. There is also a parallel increase in lambda(2)max
      and delta(max) with the same variation of the chromophore structure. Both lambda
      (2)(max)and Phidelta(max) have been optimized by introducing donor-substituted
      styryl groups at the 2,6-positions and p-cyanophenyl groups at the 9,10
      positions, respectively. The effect of a pi center on the two-photon absorption
      properties has been assessed by comparing the existing data for a variety of D-pi
      D derivatives.

PMID- 15861374
TI  - Computational study of structures and properties of metallaboranes: cobalt
      bis(dicarbollide).
AB  - A density functional study at the BP86/AE1 level is presented for the cobalt
      bis(dicarbollide) ion [3-Co-(1,2-C2B9H11)2]- (1) and selected isomers and
      rotamers thereof. Rotation of the two dicarbollide moieties with respect to each
      other is facile, as judged by the small energetic separation of the three
      rotamers located (within 11 kJ mol(-1)) and by the low barriers for their
      interconversion (at most 41 kJ mol(-1)). Among the isomers differing in carbon
      atom positions that contain two equivalent dicarbollide ligands, the 1,7 ("carbon
      apart") form [2-Co-(1,7-C2B9H11)2]- is the most stable, 121 kJ mol(-1) below 1.
      The electronic structure of 1 is characterized in terms of molecular orbitals,
      population analysis, and excitation energies from time-dependent density
      functional theory, relevant to UV/Vis spectroscopy. Experimental 11B NMR chemical
      shifts of 1 are reproduced to better than 5 ppm at the GIAO-B3LYP/II' level, and
      the computed delta(11B) values are only little affected by rotational averaging
      or the presence of a polarizable continuum. Larger such effects are found for the
      as-yet unknown 59Co chemical shift, for which a value in the range between -1800
      and -2400 ppm is predicted. Even though the accuracy achieved for the theoretical
      delta(11B) values is somewhat lower than that for heteroboranes at conventional
      ab initio levels, the level of density functional employed can afford
      qualitatively reliable chemical shifts, which can be useful in assignments and
      structural refinements of heteroboranes containing transition metal.

PMID- 15861375
TI  - Structural and binding features of cofacial bis-porphyrins with calixarene
      spacers: pac-man porphyrins that can chew.
AB  - Based on the efficient combination of calixarene spacers and acetylenic porphyrin
      derivatives, a new generation of cofacial bis-porphyrins has been synthesized.
      The first crystal structure of a cofacial bis-porphyrin-calixarene conjugate is
      reported. Their unique architectural features, analogous to those of pac-man-type
      bis-porphyrins, allow these calixarene-porphyrin conjugates to adapt their shape
      to the size of bidentate guests, such as diazabicyclo[2.2.2]octane (dabco) and
      1,4-pyrazine. The predefined, cofacial arrangement of the porphyrin moieties
      observed in the solid state and in solution results in extremely high affinities
      (in the range of 10(9) M(-1)) for these guests. The 1,3-alternate calixarene
      conformations afford "open-mouth" pac-man structures whose ability to bite on
      nitrogen bidentates depends on their functionalization. A cone conformer provides
      a much more flexible structure that exhibits the highest affinity for dabco and
      pyrazine.

PMID- 15861376
TI  - The photochemistry of 4-chlorophenol in water revisited: the effect of
      cyclodextrins on cation and carbene reactions.
AB  - The photochemistry of 4-chlorophenol (1) in water and in the presence of
      cyclodextrins has been studied by means of steady-state and time-resolved
      experiments. These have shown that 1 undergoes photoheterolysis of the C--Cl bond
      in the triplet state to yield the 4-hydroxyphenyl cation (3)2 in equilibrium with
      4-oxocyclohexa-2,5-dienylidene, (3)3. These triplet intermediates scarcely react
      with a n nucleophile, such as water, nor abstract hydrogen from this solvent,
      thus they are long-lived (approximately 1 micros). Specific trapping of both
      intermediates has been achieved. The cation adds to 2-propenol, k(add)
      approximately 1.3 x 10(8) m(-1) s(-1), to form the long-lived phenonium ion 11
      (with lambda(max) = 290 nm), which then converts to 3-(4-hydroxyphenyl)propane
      1,2-diol (10). Carbene (3)3 is trapped by oxygen to give benzoquinone and is
      reduced by D-glucose (k(q) = 8.5 x 10(6) m(-1) s(-1)) to give the phenoxyl
      radical (8) and phenol (9). Cyclodextrins have been found to trap the
      intermediates much more efficiently (k(q) = 9.4 x 10(8) m(-1) s(-1) with beta
      CD), which indicates that inclusion is involved. Ground state 1 forms inclusion
      complexes with 1:1 stoichiometry and association constants of 140 and 300 M(-1)
      with alpha- and beta-CD, respectively. Complexation does not change the
      efficiency or the mode of photofragmentation of 1; however, it does influence the
      course of the reaction because the major portion of the intermediates are reduced
      to phenol within the cavity (k'(red)> or = 5 x 10(7) s(-1)) either via a radical
      8 or via a radical cation 9(+)(.). Under these conditions, neither 2-propenol nor
      oxygen trap the intermediates to a significant extent.

PMID- 15861377
TI  - Synthesis of enantiomerically pure cyclohex-2-en-1-ols: development of novel
      multicomponent reactions.
AB  - Multicomponent reactions of aldehydes, dienophiles, and alcohols or carboxylic
      acid anhydrides have been developed for the first time. In situ generation of 1
      acyloxy- and 1-alkoxy-1,3-butadiene derivatives in toluene in the presence of
      electron-deficient dienophiles provides selective and efficient access to
      functionalized cyclohex-2-ene-1-ols in good yields. Subsequent enzyme-catalyzed
      kinetic resolution gave the corresponding enantiomers with high
      enantioselectivity.

PMID- 15861378
TI  - Inhibition of mitosis by glycopeptide dendrimer conjugates of colchicine.
AB  - Glycopeptide dendrimers have been prepared bearing four or eight identical
      glycoside moieties at their surface (beta-glucose, alpha-galactose, alpha-N
      acetyl-galactose, or lactose), natural amino acids within the branches (Ser, Thr,
      His, Asp, Glu, Leu, Val, Phe), 2,3-diaminopropionic acid as the branching unit,
      and a cysteine residue at the core. These dendrimers have been used as drug
      delivery devices for colchicine. Colchicine was attached to the dendrimers at the
      cysteine thiol group through a disulfide or thioether linkage. The biological
      activities of the glycopeptide dendrimer conjugates were evaluated in HeLa tumor
      cells and non-transformed mouse embryonic fibroblasts (MEFs). The concentrations
      of glycopeptide dendrimer drug conjugates required to achieve inhibition of cell
      proliferation by interference with the tubulin system were found to be higher
      (IC50 > 1 microM) compared to the required colchicine concentration. On the other
      hand, the glycopeptide dendrimer conjugates inhibited the proliferation of HeLa
      cells 20-100 times more effectively than the proliferation of MEFs. In
      comparison, non-glycosylated dendrimers and colchicine itself showed a
      selectivity of 10-fold or less for HeLa cells.

PMID- 15861379
TI  - A metal-organic framework with the zeolite MTN topology containing large cages of
      volume 2.5 nm3.

PMID- 15861380
TI  - Drastic effect of a single base difference between human and tetrahymena telomere
      sequences on their structures under molecular crowding conditions.

PMID- 15861381
TI  - Preparation of chitosan-g-polycaprolactone copolymers through ring-opening
      polymerization of epsilon-caprolactone onto phthaloyl-protected chitosan.
AB  - The new biodegradable chitosan graft copolymer, chitosan-g-polycaprolactone, was
      synthesized by the ring-opening graft copolymerization of epsilon-caprolactone
      onto phthaloyl-protected chitosan (PHCS) at the hydroxyl group in the presence of
      tin(II) 2-ethylhexanoate catalyst via a protection-graft-deprotection procedure.
      Toluene acted as a swelling agent in this heterogeneous system. The grafting
      reactions were conducted with various PHCS/monomer/toluene feed ratios to obtain
      chitosan-g-polycaprolactone copolymers with various polycaprolactone contents.
      The chemical structure of the chitosan-g-polycaprolactone was characterized by
      Fourier transform infrared and one- and two-dimensional NMR spectroscopy. After
      deprotection, the phthaloyl group was removed and the amino group was
      regenerated. Thus the obtained chitosan-g-polycaprolactone was an amphoteric
      hybrid with a large amount of free amino groups and hydrophobic polycaprolactone
      side chains. Some properties of the final product were also investigated, such as
      crystallinity, thermal property, and solubility.

PMID- 15861382
TI  - Physical and functional interactions between the human DNMT3L protein and members
      of the de novo methyltransferase family.
AB  - The de novo methyltransferase-like protein, DNMT3L, is required for methylation
      of imprinted genes in germ cells. Although enzymatically inactive, human DNMT3L
      was shown to act as a general stimulatory factor for de novo methylation by
      murine Dnmt3a. Several isoforms of DNMT3A and DNMT3B with development-stage and
      tissue-specific expression patterns have been described in mouse and human, thus
      bringing into question the identity of the physiological partner(s) for
      stimulation by DNMT3L. Here, we used an episome-based in vivo methyltransferase
      assay to systematically analyze five isoforms of human DNMT3A and DNMT3B for
      activity and stimulation by human DNMT3L. Our results show that human DNMT3A,
      DNMT3A2, DNMT3B1, and DNMT3B2 are catalytically competent, while DNMT3B3 is
      inactive in our assay. We also report that the activity of all four active
      isoforms is significantly increased upon co-expression with DNMT3L, albeit to
      varying extents. This is the first comprehensive description of the in vivo
      activities of the poorly characterized human DNMT3A and DNMT3B isoforms and of
      their functional interactions with DNMT3L. To further elucidate the mechanism by
      which DNMT3L stimulates DNA methylation, we have mapped in detail the domains
      that mediate interaction of human DNMT3L with human DNMT3A and DNMT3B. Our
      results show that the C-terminus of DNMT3L is the only region required for
      interaction with DNMT3A and DNMT3B and that interaction takes place through the C
      terminal catalytic domain of DNMT3A and DNMT3B. The implications of these
      findings for the regulation of de novo methyltransferases and genomic imprinting
      are discussed. This article contains Supplementary Material available at
      http://www.mrw.interscience.wiley.com/suppmat/0730
      2312/suppmat/2005/95/chen.html.

PMID- 15861383
TI  - Ring-substituted benzohydroxamic acids: 1H, 13C and 15N NMR spectra and NH-OH
      proton exchange.
AB  - NMR spectra (1H, 13C, 15N) of para- and meta-substituted benzohydroxamic acids
      were studied in dry dimethyl sulfoxide solutions. The 13C chemical shifts were
      very close to those found by cross-polarization magic angle spinning in solids,
      the hydroxamic (not hydroximic) structure of which is unambiguous. The hydroxamic
      structure of these acids in DMSO solutions was proved independently by their 15N
      chemical shifts. The 15N and 1H chemical shifts of the NH-OH fragment showed
      excellent mutual dependences and dependences on the nature of the ring
      substituent. According to these dependences and ab initio energy calculations,
      all the acids assume the same Z conformation. Proton exchange between hydroxamic
      OH and NH groups in DMSO proceeded by both intra- and intermolecular exchange and
      the rates did not exhibit any simple relationship to the substituent constants.

PMID- 15861385
TI  - Application of InChI to curate, index, and query 3-D structures.
AB  - The HIV structural database (HIVSDB) is a comprehensive collection of the
      structures of HIV protease, both of unliganded enzyme and of its inhibitor
      complexes. It contains abstracts and crystallographic data such as inhibitor and
      protein coordinates for 248 data sets, of which only 141 are from the Protein
      Data Bank (PDB). Efficient annotation, indexing, and querying of the inhibitor
      data is crucial for their effective use for technological and industrial
      applications. The application of IUPAC International Chemical Identifier (InChI)
      to index, curate, and query inhibitor structures HIVSDB is described.

PMID- 15861386
TI  - Dynamic 13C NMR studies of ligand exchange in linear (d10) silver(I) and gold(I)
      and square-planar (d8) rhodium(I) homoleptic metal carbonyl cations in
      superacidic media.
AB  - The dynamic CO exchange of the monovalent metal carbonyl cations [Ag(13CO)]+,
      [Au(13CO)2]+-Au(13CO) SO3F and [Rh(12CO)4-x(13CO)x]+ (x < or = 1) in superacidic
      solutions was studied by variable-temperature 13C NMR methods. The exchange rates
      are strongly dependent on the acidity of the solvent, the concentration of metal
      carbonyl cations and temperature. Whereas a suitable exchange rate of the Ag(I)
      system is only accessible in magic acid (HSO3F-SbF5), the more stable Au(I) and
      Rh(I) systems were studied in the less acidic fluorosulfuric acid. Selected
      solutions of Ag(I), Rh(I) and Au(I) yielded activation barriers deltaG* of 42.7,
      43.5, and 56.2 kJ mol(-1) respectively.

PMID- 15861387
TI  - Pyrazolino[60]fullerene-oligophenylenevinylene dumbbell-shaped arrays: synthesis,
      electrochemistry, photophysics, and self-assembly on surfaces.
AB  - Symmetrically substituted oligophenylenevinylene (OPV) derivatives bearing
      terminal p-nitrophenylhydrazone groups have been prepared and used for the
      synthesis of dumbbell-shaped bis(pyrazolino[60]fullerene)-OPV systems. In these
      triad arrays, the OPV-type fluorescence is dramatically quenched as a consequence
      of ultrafast OPV-->C60 singlet energy transfer. In its turn the fullerene singlet
      state is quenched by pyrazoline-->C60 electron transfer, in line with the
      behavior of the corresponding reference fullerene molecule. The occurrence of
      electron transfer in the multicomponent arrays is evidenced by recovery of
      fullerene fluorescence at 77 K in CH2Cl2 and in toluene at 298 K. Under these
      conditions the OPV-->C60 energy transfer is unaffected. The rate of this process
      turns out to be higher for the OPV trimer than for the corresponding pentameric
      OPV arrays, in agreement with energy-transfer theory expectations. Scanning
      tunneling microscopy (STM) and scanning force microscopy (SFM) revealed that the
      bis(pyrazolino[60]fullerene)-OPV can self-assemble into ordered layered
      crystalline architectures on the basal plane of highly oriented pyrolitic
      graphite.

PMID- 15861388
TI  - A guideline to the design of molecular-based materials with long-lived
      photomagnetic lifetimes.
AB  - Materials presenting a stable and reversible switch of physical properties in the
      solid state are of major interest either for fundamental interests or potential
      industrial applications. In this context, the design of metal complexes showing a
      light-induced crossover from one spin state to another, leading to a major change
      of magnetic and optical properties, is probably one of the most appealing
      challenges. The so-denoted spin-crossover materials undergo, in some cases, a
      reversible photoswitch between two magnetic states, but, unfortunately, lifetimes
      of the photomagnetic states for compounds known so far are long enough only at
      low temperatures; this prohibits any applications. We have measured and collected
      the temperatures above which the photomagnetic effect disappears for more than
      sixty spin-crossover compounds. On the basis of this large data base, a
      correlation between the nature of the coordination sphere of the metal and the
      photomagnetic lifetime can be drawn. Such correlation allows us to propose here a
      general guideline for the rational design of materials with long-lived
      photomagnetic lifetimes. This result clearly opens the way towards room
      temperature photonic materials, based on the spin-crossover phenomenon, which
      will be of great interest for future communication devices.

PMID- 15861389
TI  - Orientational isomerism and binding ability of nonsymmetrical guests encapsulated
      in a self-assembling heterodimeric capsule.
AB  - The ability of a guest to induce the assembly of tetracarboxyl-cavitand 1 and
      tetra(3-pyridyl)-cavitand 2 into a heterodimeric capsule 12, and the
      orientational isomerism of nonsymmetrical p-disubstituted-benzene guests
      encapsulated in 12, are described. For example, the ability of a guest to induce
      the assembly of guest subset(12) increases in the order p-iodoaniline< or =p
      chloroanisole < p-bromoanisole < N-methyl-p-iodoaniline < p-iodoanisole. For
      these five guests encapsulated in 12, the halogen atoms are specifically oriented
      with respect to the cavity of the 2 unit. By contrast, the orientational isomeric
      selectivities of p-chloroiodobenzene, p-bromoiodobenzene, and p-methylanisole
      encapsulated in 12 are quite low, in the range of 1:1.7 to 1:1. The ortho-fluoro
      derivatives of these three guests, however, are encapsulated in 12 with a highly
      selective orientation, in which the substituent next to the fluorine atom greatly
      prefers the cavity of the 2 unit to that of the 1 unit.

PMID- 15861390
TI  - Recognizing protein folds by cluster distance geometry.
AB  - Cluster distance geometry is a recent generalization of distance geometry whereby
      protein structures can be described at even lower levels of detail than one point
      per residue. With improvements in the clustering technique, protein conformations
      can be summarized in terms of alternative contact patterns between clusters,
      where each cluster contains four sequentially adjacent amino acid residues. A
      very simple potential function involving 210 adjustable parameters can be
      determined that favors the native contacts of 31 small, monomeric proteins over
      their respective sets of nonnative contacts. This potential then favors the
      native contacts for 174 small, monomeric proteins that have low sequence identity
      with any of the training set. A broader search finds 698 small protein chains
      from the Protein Data Bank where the native contacts are preferred over all
      alternatives, even though they have low sequence identity with the training set.
      This amounts to a highly predictive method for ab initio protein folding at low
      spatial resolution.

PMID- 15861391
TI  - Reversal of some viral IL-6 electrostatic properties compared to IL-6 contributes
      to a loss of alpha receptor component recruitment.
AB  - Human interleukin-6 (hIL-6) is a pleiotropic mediator of activation and
      proliferation across a large number of different cell types. Human herpesvirus-8
      (HHV-8) has been associated with classical and AIDS-related Kaposi's sarcoma
      (KS). HHV-8 encodes viral IL-6 (vIL-6), a functional homolog of human interleukin
      6, that promotes the growth of KS and of some lymphoma cells. Signaling induced
      by human IL-6 requires recruitment of the glycoprotein gp130, which acts as the
      signal transducing chain, and of IL-6Ralpha, which is necessary for cognate
      recognition and high affinity receptor complex formation. In contrast, the
      formation of a functional complex between vIL-6 and gp130 does not require the
      presence of IL-6Ralpha. The physico-chemical properties of vIL-6 have been
      analyzed and compared to those of hIL-6 and of the receptor chains, gp130 and IL
      6Ralpha. Interaction sites on vIL-6 involve more hydrophobic residues than those
      of hIL-6. The electrostatic fields induced by vIL-6 and IL-6Ralpha are repulsive
      and prevent interaction between vIL-6 and IL-6Ralpha, whereas the electrostatic
      field induced by hIL-6 steers the complex formation with IL-6Ralpha.
      Subsequently, electrostatic binding free energy in the vIL-6/IL-6Ralpha complex
      is destabilizing, whereas it is stabilizing in the complex comprising hIL-6.
      These properties result from charge reversals between viral and human IL-6, an
      unusual phenomenon of amino acid substitutions within a homologous protein
      family. This suggests a selection pressure for vIL-6 to by-pass the IL-6Ralpha
      control of host defense against virus infection. This selection pressure has
      yielded the reversal of electrostatic properties of vIL-6 when compared to hIL-6.

PMID- 15861392
TI  - Groucho corepressor proteins regulate otic vesicle outgrowth.
AB  - The Groucho/Tle family of corepressor proteins is known to regulate multiple
      developmental pathways. Applying the dominant-negative effect of the short member
      Aes, we demonstrate here a critical role of this gene family also for ear
      development. Misexpression of Aes in medaka embryos resulted in reduced size or
      loss of otic vesicles, whereas overexpression of the full-length Groucho protein
      Tle4 gave the opposite phenotype. These results are in close agreement with
      phenotypes observed for eye formation, suggesting a similar role for Groucho/Tle
      proteins in the developmental pathways of both sensory organs. Furthermore, by
      using the heat-inducible HSE promoter, we observed reversible branching of the
      embryonic axis upon Aes misexpression, indicating a transient duplication of the
      organizer. Groucho proteins, therefore, are critical for organizer maintenance.

PMID- 15861393
TI  - Serine protease HtrA1 is developmentally regulated in trophoblast and uterine
      decidual cells during placental formation in the mouse.
AB  - Development of a hemochorial placenta involves trophoblast proliferation,
      differentiation, and invasion into the uterus to promote blood flow to the
      embryo. Trophoblast invasion is tightly controlled by expression of specific
      proteases in the trophoblast and highly coordinated activities in the uterus. One
      uterine event essential for placentation is the developmentally regulated
      formation and regression of the decidua. In mice, decidual regression takes place
      in a temporal- and spatial-specific manner that is coordinated with placental
      development. In this study, we identified that the serine protease HtrA1 (high
      temperature requirement factor A1) was specifically expressed in differentiated
      trophoblast cells, especially the giant cells, during the early stages of
      placental development. A high level of HtrA1 expression was also detected in
      decidua capsularis specifically at the decidual-trophoblast interface where
      active involution occurs. Thus, we have identified a previously unknown role for
      HtrA1 as a protease potentially important for trophoblast
      differentiation/invasion and uterine decidual regression during placental
      development.

PMID- 15861394
TI  - Induction of an epithelial to mesenchymal transition in human immortal and
      malignant keratinocytes by TGF-beta1 involves MAPK, Smad and AP-1 signalling
      pathways.
AB  - Recent data indicate that transforming growth factor-beta1 (TGF-beta1) can act to
      promote tumour progression in the late stages of carcinogenesis. The mechanism by
      which this occurs is unknown although a ligand-induced epithelial-mesenchymal
      transition (EMT) is thought to be important. In this study, we demonstrate that
      active Ras is required for TGF-beta1-induced EMT in human keratinocytes and that
      epidermal growth factor (EGF) can substitute for mutant Ras. EMT was reversed by
      the removal of TGF-beta1. Under conditions of TGF-beta1-induced EMT, cells were
      growth inhibited by the ligand resulting in G1 arrest. In cells containing normal
      Ras, TGF-beta1-activated ERK and p38 mitogen-activated protein kinases (MAPKs),
      and levels of activation were further increased by co-treatment with EGF.
      Inhibition of MAPK pathways and Smad2/3 signalling blocked the induction of EMT
      by TGF-beta1. Further, inhibition of the AP-1 transcriptional complex by [6]
      Gingerol, or by the ectopic expression of JDP2, blocked TGF-beta1-induced EMT and
      conversely, stimulation of AP-1 by 12-O-tetradecanoylphorbol 13-acetate (TPA)
      substituted for EGF in the induction of EMT by TGF-beta1 in cells containing
      normal Ras. The presence of oncogenic Ras, the treatment of cells with EGF, or
      the treatment of cells with TPA to activate AP-1, potentiated TGF-beta1-induced
      Smad-dependent transcription, an effect that was attenuated by the inhibition of
      MAPKs and AP-1. The results demonstrate that active Ras and TGF-beta1 co-operate
      to reversibly induce EMT in human keratinocytes by mechanisms that involve MAPKs,
      Smad2/3 and AP-1. Further we demonstrate that MAPK/AP-1 signalling enhances Smad
      transcriptional activity under conditions associated with TGF-beta1-induced EMT.

PMID- 15861395
TI  - Differential roles of XRCC2 in homologous recombinational repair of stalled
      replication forks.
AB  - Homologous recombination is an important mechanism in DNA replication to ensure
      faithful DNA synthesis and genomic stability. In this study, we investigated the
      role of XRCC2, a member of the RAD51 paralog family, in cellular recovery from
      replication arrest via homologous recombination. The protein expression of XRCC2,
      as well as its binding partner RAD51D, is dramatically increased in S- and G2
      phases, suggesting that these proteins function during and after DNA synthesis.
      XRCC2 mutant irs1 cells exhibit hypersensitivity to hydroxyurea (HU) and are
      defective in the induction of RAD51 foci after HU treatment. In addition, the HU
      induced chromatin association of RAD51 is deficient in irs1 mutant.
      Interestingly, irs1 cells are only slightly sensitive to thymidine and able to
      form intact RAD51 foci in S-phase cells arrested with thymidine. Irs1 cells
      showed increased level of chromatin-bound RAD51 as well as the wild type cells
      after thymidine treatment. Both HU and thymidine induce gamma-H2AX foci in
      arrested S-phase nuclei. These results suggest that XRCC2 is involved in repair
      of HU-induced damage, but not thymidine-induced damage, at the stalled
      replication forks. Our data suggest that there are at least two sub-pathways in
      homologous recombination, XRCC2-dependent and -independent, for repair of stalled
      replication forks and assembly of RAD51 foci following replication arrest in S
      phase.

PMID- 15861396
TI  - Conserved expression of a novel gene during gonadal development.
AB  - We isolated the novel gene Gonad Expressed Transcript (GET) from a chicken
      embryonic gonad library enriched for differentially expressed male transcripts.
      Chicken GET encodes a predicted protein containing a Pfam-B 30624 domain with
      homology to a putative orthologue in mammals. Chicken GET expression was confined
      to the developing urogenital system. It was first detected in the glomerulus of
      the mesonephros of both sexes from embryonic day (E) 2.5. At E4.5, expression
      switches to the gonad of both sexes and then localizes to the gonadal cortex. We
      isolated the putative mouse orthologue and examined expression in the mouse
      embryo. Gonadal expression was conserved. Ovarian expression localized to the
      cortex as in the chicks. However, in contrast to the chicken, testis expression
      localized to the cords. In the adult, GET is expressed in the ovary but not the
      testis of both the chicken and the mouse. Expression of GET in the mullerian
      duct, wolffian duct, metanephric kidney, and external genitalia, suggests that
      GET may play a wider role in the development of the urogenital system.

PMID- 15861397
TI  - Mammalian Groucho homologs: redundancy or specificity?
AB  - The proteins termed TLE in humans, Grg in mice and Groucho in Drosophila
      constitute a family of transcriptional corepressors. In mammalians there are five
      different genes encoding an even larger number of proteins. Interactions between
      these TLE/Grg proteins and an array of transcription factors has been described.
      But is there any specificity? This review tries to make a case for a non
      redundant function of individual TLE/Grg proteins. The specificity may be brought
      about by a tightly controlled temporo-spatial expression pattern, post
      translational modifications, and subtle structural differences leading to
      distinct preferences for interacting transcription factors. A confirmation of
      this concept will ultimately need to come from genetic experiments.

PMID- 15861398
TI  - Major contribution of the multidrug transporter P-glycoprotein to reduced
      susceptibility of poly(ADP-ribose) polymerase-1 knock-out cells to doxorubicin
      action.
AB  - Inactivation of poly(ADP-ribose) polymerase-1 (PARP-1) has been shown to
      potentiate the cytotoxicity of distinct DNA targeting agents including
      topoisomerase I inhibitors. On the other hand, the PARP-1 deficient cells
      exhibited resistance to conventional inhibitors of topoisomerase II such as
      etoposide or doxorubicin (DOX). Recently, we observed the extreme sensitivity of
      PARP-1 knock-out (KO) cells to C-1305, a new biologically active triazoloacridone
      compound. C-1305 permanently arrested the cells in G2-phase of the cell-cycle.
      These observations prompted us to investigate more thoroughly the susceptibility
      of PARP-1 KO cells to DOX and to examine the effect of DOX on the progression of
      cell-cycle. We determined the uptake of DOX and P-glycoprotein (P-gp) expression
      in mouse cells and compared it with that in human myeloma 8226/Dox40 cells
      overexpressing P-gp. Exposure of mouse cells to DOX revealed a reduced drug
      uptake in cells lacking PARP-1. However, combined treatment with verapamil, a
      potent MDR modulator increased the DOX accumulation. Detailed immunoblotting
      experiments revealed an approximately threefold higher P-gp level in PARP-1 KO
      cells as compared with normal counterparts. Interestingly, DOX induced in normal
      fibroblasts very rapidly G2 arrest whereas in PARP-1 KO cells it blocked
      primarily the transition between S and G2 resulting in the increase of cells
      remaining in S-phase. This coincided with the lack of the site-specific
      phosphorylation of CDK2. Simultaneous inhibition of P-gp in cells lacking PARP-1
      resulted in an accumulation of cells in G2. Exposure of mouse cells to high DOX
      dose activated significantly caspase-3/7 in PARP-1 KO cells.

PMID- 15861399
TI  - Regulation of androgen receptor levels: implications for prostate cancer
      progression and therapy.
AB  - Androgen deprivation has been the standard therapy for advanced and metastatic
      prostate cancer for over half a century, as prostate tumors are initially
      dependent on androgens for growth and survival. Unfortunately, in most patients
      undergoing androgen ablation, relapse (recurrent tumor growth) eventually occurs.
      The actions of the principal androgens, testosterone and dihydrotestosterone
      (DHT), are mediated via androgen receptors (ARs), ligand-activated transcription
      factors that belong to the nuclear receptor superfamily. Because of the presence
      of transcriptionally active ARs in tumors from recurrent or androgen-independent
      disease, there is a heightened interest in new therapeutic paradigms that target
      the AR and its regulatory pathways. The regulation of AR levels is highly complex
      with control exerted by several pathways and in a cell-, tissue-, and
      developmental-stage specific manner. Androgens are important regulators of AR
      mRNA and protein through transcriptional and post-transcriptional mechanisms.
      This article reviews the evidence implicating the AR in recurrent prostate cancer
      and discusses the multiple mechanisms that regulate AR levels in normal and
      neoplastic cells. The complexity of AR regulation suggests that there will be an
      ample array of potential new drug targets for modulating levels of this receptor,
      a key signaling molecule in prostate cancer.

PMID- 15861400
TI  - Family clustering of Baeyer-Villiger monooxygenases based on protein sequence and
      stereopreference.

PMID- 15861401
TI  - Embryonic staging system for the short-tailed fruit bat, Carollia perspicillata,
      a model organism for the mammalian order Chiroptera, based upon timed pregnancies
      in captive-bred animals.
AB  - There are approximately 4,800 extant species of mammals that exhibit tremendous
      morphological, physiological, and developmental diversity. Yet embryonic
      development has been studied in only a few mammalian species. Among mammals, bats
      are second only to rodents with regard to species number and habitat range and
      are the most abundant mammals in undisturbed tropical regions. Bat development,
      though, remains relatively unstudied. Here, we describe and illustrate a staging
      series of embryonic development for the short-tailed fruit bat, Carollia
      perspicillata, based on embryos collected at timed intervals after captive
      matings. As Carollia can be readily maintained and propagated in captivity and is
      extremely abundant in the wild, it offers an attractive choice as a chiropteran
      model organism. This staging system provides a framework for studying Carollia
      embryogenesis and should prove useful as a guide for embryological studies of
      other bat species and for comparisons with other orders of mammals.

PMID- 15861402
TI  - Second branchial arch lineages of the middle ear of wild-type and Hoxa2 mutant
      mice.
AB  - Our current understanding of the evolution of the mammalian middle ear was first
      suggested by embryological studies from the 19th century. Here, site-specific
      recombinase-mediated lineage tracing was used to define the second branchial arch
      contribution to the middle ear of wild-type and Hoxa-2 mutant embryos. The
      processus brevis of the malleus was found to arise from second arch tissues,
      making it the likely homologue of the retroarticular process of nonmammalian
      tetrapods. The second arch also formed a portion of the otic capsule. In light of
      avian lineage studies, second arch cells were probably incorporated into the otic
      capsule before avian and mammalian lineages diverged. In Hoxa2 mutant embryos,
      middle ear skeletal duplications occurred at sites where first and second arch
      elements are normally apposed. The dorsoventral positions at which second arch
      skeletal elements formed and the early migration of second arch neural crest
      cells were not altered by the absence of Hoxa2 function.

PMID- 15861403
TI  - Cell lineage of primary and secondary enamel knots.
AB  - Recent research indicates that control of cusp morphology involves a signalling
      center at the heart of the developing tooth germ, known as the enamel knot. The
      primary enamel knot forms in both incisors and molar tooth germs at the cap stage
      of tooth development. Secondary and tertiary enamel knots only develop in molar
      tooth germs. These sit at the sites of future cusp tips from the early bell stage
      of tooth development. In studies describing the relationship between the primary
      and secondary enamel knots, it is often assumed that there is a cellular
      continuity between these structures, such that cells from the primary enamel knot
      physically contribute to the secondary enamel knots. We have devised a method
      whereby the developing tooth germ can be cultured in frontal slices with the
      enamel knot visible. The fate of the primary enamel knot cells can then be
      followed by 1,1', di-octadecyl-3,3,3',3',-tetramethylindo-carbocyanine
      perchlorate (DiI) labeling. Using this method, no cells of the primary enamel
      knot were seen to move toward the developing secondary enamel knots. Thus,
      although the primary and secondary enamel knots have a close molecular and
      functional relationship in molar development, they are not actually derived from
      the same cells.

PMID- 15861404
TI  - Comparative expression analysis of transcription factor genes in the endostyle of
      invertebrate chordates.
AB  - The endostyle of invertebrate chordates is a pharyngeal organ that is thought to
      be homologous with the follicular thyroid of vertebrates. Although thyroid-like
      features such as iodine-concentrating and peroxidase activities are located in
      the dorsolateral part of both ascidian and amphioxus endostyles, the structural
      organization and numbers of functional units are different. To estimate
      phylogenetic relationships of each functional zone with special reference to the
      evolution of the thyroid, we have investigated, in ascidian and amphioxus, the
      expression patterns of thyroid-related transcription factors such as TTF-2/FoxE4
      and Pax2/5/8, as well as the forkhead transcription factors FoxQ1 and FoxA.
      Comparative gene expression analyses depicted an overall similarity between
      ascidians and amphioxus endostyles, while differences in expression patterns of
      these genes might be specifically related to the addition or elimination of a
      pair of glandular zones. Expressions of Ci-FoxE and BbFoxE4 suggest that the
      ancestral FoxE class might have been recruited for the formation of thyroid-like
      region in a possible common ancestor of chordates. Furthermore, coexpression of
      FoxE4, Pax2/5/8, and TPO in the dorsolateral part of both ascidian and amphioxus
      endostyles suggests that genetic basis of the thyroid function was already in
      place before the vertebrate lineage.

PMID- 15861405
TI  - Embryonic and posthatching development of the barn owl (Tyto alba): reference
      data for age determination.
AB  - The normal development of the barn owl was documented with the intent of
      providing a guideline for determining the maturational stage of embryos and
      posthatching individuals. Embryonic development up to stage 39 could be well
      described using the well-known developmental atlas for the chicken (Hamburger and
      Hamilton [1951] J. Morphol. 88:49-92). For later stages, limb size was
      established as a suitable indicator. In addition, measuring the egg's
      vascularized area through candling was found to be a useful, noninvasive method
      for staging very early embryos, up to stage 25. An average relationship between
      incubation period and embryonic stage was derived, which showed that development
      in the barn owl initially lags that in the chicken. For posthatching individuals,
      skeletal measures (tarsal and ulnar length, skull width and length) were the most
      reliable parameters for judging maturation, up to 1 month. For older individuals,
      feather development (e.g., length of primary wing feathers) provided the only
      cue.

PMID- 15861406
TI  - Photoactivatable green fluorescent protein as a single-cell marker in living
      embryos.
AB  - Selective marking of a single cell within an embryo is often difficult to perform
      with existing methods. Here, we report a minimally invasive optical technique
      that uses 405-nm laser light to photoactivate a variant of green fluorescent
      protein (PAGFP). Single cells and small groups of cells (n < 10) are successfully
      marked, from a region of cells injected and electroporated with PAGFP, in both
      whole chick embryo explants and in ovo. Photoactivated cells display normal cell
      migratory behaviors and retain a bright GFP signal for at least 24 hr when
      followed with confocal time-lapse microscopy. We determined that using a low
      magnification objective (approximately x 10) and low laser power (approximately 1
      10%) leads to a steady increase in fluorescence signal within a photoactivated
      cell and minimizes photobleaching. The utility of PAGFP photoactivation was
      tested to address a specific question in developmental biology. Specifically, we
      asked whether neighboring migratory cells that emerge from the hindbrain and
      invade surrounding peripheral tissues maintain neighbor relationships while
      traveling to the destination sites. We found that some neural crest do not
      maintain neighbor relationships, such that two neighboring cells near the neural
      tube cells may populate different branchial arches. The ability to optically
      photoactivate PAGFP in a single or small group of cells and follow individual
      cell migratory behaviors within a living embryo offers a powerful, minimally
      invasive cell marking tool for precise, in vivo cell migration studies.

PMID- 15861407
TI  - Tryptophan to phenylalanine substitutions allow differentiation of short- and
      long-range conformational changes during denaturation of goat alpha-lactalbumin.
AB  - To test the occurrence of local particularities during the unfolding of Ca2+
      loaded goat alpha-lactalbumin (GLA) we replaced Trp60 and -118, either one or
      both, by Phe. In contrast with alternative studies, our recombinant alpha
      lactalbumins are expressed in Pichia pastoris and do not contain the extra N
      terminal methionine. The substitution of Trp60 leads to a reduction of the global
      stability. The effect of the Trp118Phe substitution on the conformation and
      stability of the mutant, however, is negligible. Comparison of the fluorescence
      spectra of these mutants makes clear that Trp60 and -118 are strongly quenched in
      the native state. They both contribute to the quenching of Trp26 and -104
      emission. By the interplay of these quenching effects, the fluorescence intensity
      changes upon thermal unfolding of the mutants behave very differently. This is
      the reason for a discrepancy of the apparent transition temperatures derived from
      the shift of the emission maxima (Tm,Fl lambda) and those derived from DSC
      (Tm,DSC). However, the transition temperatures derived from fluorescence
      intensity (Tm,Fl int) and from DSC (Tm,DSC), respectively, are quite similar, and
      thus, no local rearrangements are observed upon heat-induced unfolding. At room
      temperature, the occurrence of specific local rearrangements upon GdnHCl-induced
      denaturation of the different mutants is deduced from the apparent free energies
      of their transition state obtained from stopped-flow fluorescence measurements.
      By phi-value analysis it appears that, while the surroundings of Trp118 are
      exposed in the kinetic transition state, the surroundings of Trp60 remain native.

PMID- 15861408
TI  - Analysis of the proepicardium-epicardium transition during the malformation of
      the RXRalpha-/- epicardium.
AB  - The epicardium of the heart originates from a cluster of mesothelial-derived
      cells that develop beneath the sinus venosus in the embryonic day (E) 9.0-9.5
      mouse. The subsequent proepicardium-epicardium transition that forms the
      epicardial layer of epithelial cells covering the myocardial surface is nearly
      complete by E10.0-E10.5 and results in a fully covered heart by E11.0. In this
      study, we show that an established model of congenital heart disease, the
      retinoid X receptor alpha knockout (RXRalpha-/-) embryo, displays a malformed
      epicardium. At E10.0-E10.5, the RXRalpha-/- has several large regions of
      myocardium that remain bare. Furthermore, by E11.5-E12.5, when a complete
      epithelial layer is formed in the mutant, large regions of the epicardium become
      distended from the underlying myocardium. Close examination of the E9.5 mutant
      revealed an elevated apoptosis level within the proepicardial cluster of
      mesothelial cells. Additionally, among the extracellular matrix proteins
      analyzed, expression of fibronectin was elevated in the RXRalpha-/- as assessed
      by immunostaining in paraffin-embedded sections and proepicardial explants. We
      propose that these events contribute to a developmental delay in the formation of
      the epicardium, which leads to an abnormal epicardium and ultimately contributes
      to the cardiac malformations seen in the RXRalpha-/-.

PMID- 15861409
TI  - Weekly vinblastine in pediatric low-grade glioma patients with carboplatin
      allergic reaction.
AB  - BACKGROUND: Carboplatin-based regimens have demonstrated activity in unresectable
      low-grade glioma (LGG) in children. Despite an interesting toxicity profile, the
      use of these regimens has been limited by the development of carboplatin
      hypersensitivity reaction (HSR) in up to 30% of patients. Desensitization has
      been the recommended approach for HSR. However, no guidelines have existed to aid
      physicians when carboplatin desensitization techniques fail. METHODS: A pilot
      study of monotherapy with weekly vinblastine for LGG in 9 children who developed
      carboplatin HSR on a carboplatin and vincristine regimen was performed. RESULTS:
      Vinblastine toxicity was moderate and readily manageable. None of the 9 patients
      had disease progression on therapy. Magnetic resonance imaging evaluation of
      tumor size from diagnosis to the end of vinblastine treatment showed 1 complete
      response (CR), 1 partial response (PR), 5 objective effects (OE), and 2 stable
      diseases (SD). CONCLUSIONS: This experience suggested that weekly vinblastine has
      a good efficacy to toxicity ratio in the treatment of LGG and can be a valuable
      option for children who develop severe HSR.

PMID- 15861411
TI  - Supratentorial extraventricular ependymal neoplasms: a clinicopathologic study of
      32 patients.
AB  - BACKGROUND: Published research on the clinicopathologic features of
      extraventricular ependymal neoplasms of the cerebral hemispheres has been scant.
      METHODS: Thirty-two archival cases were studied to investigate the prognostic
      impact of clinicopathologic parameters including flow cytometry, the
      proliferation (Ki-67) labeling index, and p53 expression. RESULTS: Among these 32
      cases were 2 subependymomas, 19 ependymomas, and 11 anaplastic ependymomas. No
      significant gender predilection was observed, and 45% of patients were in their
      second or third decade of life. The left cerebral hemisphere was 1.5 times more
      commonly involved. On available imaging studies, lesions were often cystic, with
      or without a mural nodule. Tumors expressed glial fibrillary acidic protein
      (87%), S-100 protein (77%), cytokeratin (43%), and epithelial membrane antigen
      (17%). Ki-67 proliferation index paralleled tumor grade. Immunoreactivity for p53
      protein was observed in the 2 cases of subependymoma, in 10 of 11 anaplastic
      ependymomas, and in 6 of 17 ependymomas. Flow cytometry performed in 27 tumors
      revealed diploidy in 20 cases and aneuploidy in 4 cases (3 anaplastic and 1
      classic ependymomas), with S-phase fraction ranging from 0.2-9.7. Eleven subjects
      were additionally treated with radiotherapy, and 3 with chemotherapy. Follow up
      was available in 25 (78%) patients. CONCLUSIONS: The results of the current study
      suggest that there is no significant relation between histopathology, Ki-67
      proliferation index, p53 immunolabeling, tumor ploidy, and biologic behavior.

PMID- 15861412
TI  - Interferon alpha therapy for patients with essential thrombocythemia: final
      results of a phase II study initiated in 1986.
AB  - BACKGROUND: In 1986, a Phase II trial of recombinant interferon-alpha (IFN-alpha)
      was initiated as therapy for patients with essential thrombocythemia (ET).
      METHODS: Patients were treated with subcutaneous IFN-alpha at a dose of 5 x 10(6)
      units/m(2) daily. In responding patients, the therapy lasted at least 3 years.
      RESULTS: Twenty-three patients (14 females and 9 males; median age, 41 years; age
      range, 20-63 years) with a median platelet count of 1350 x 10(9)/L were treated.
      After a median follow-up of 174 months (14.5 years), 15 of 20 evaluable patients
      (75%) responded, including 14 patients who achieved a complete hematologic
      response (CHR) (6 of them with bone marrow remission) and 1 patient who
      demonstrated a partial response. The median time to response was 6 months (range,
      0.5-36 months), and the median response duration was 48 months (range, 5-114
      months). Seven patients who achieved a CHR and were taken off therapy after they
      completed 3 years of maintenance therapy sustained their response for a median of
      28 months. No symptoms or signs of thrombosis or hemorrhage were observed in
      responding patients. Eleven of 14 patients (78%) who achieved a CHR developed a
      recurrence, and 2 of 5 patients with recurrences who were rechallenged with IFN
      alpha achieved a second response. The treatment was tolerated relatively well.
      CONCLUSIONS: IFN-alpha was safe and effective therapy for patients with ET, and
      the ability of IFN-alpha to reverse disease pathology and possibly modify the
      clinical course of patients with ET warrants its investigation in larger,
      prospective trials.

PMID- 15861413
TI  - The role of ultrasound imaging in diagnosing and investigating early pregnancy
      failure.
AB  - The advent of high-resolution transvaginal ultrasound (TVS) has revolutionized
      our understanding of the pathophysiology and the management of early pregnancy
      failure. Knowledge of the ultrasound appearances of normal early pregnancy
      development and a good understanding of its pitfalls are essential for the
      diagnosis and management of early pregnancy failure. Ultrasound imaging has
      rapidly replaced all other techniques used to study normal human development in
      the first trimester, and ultrasound features of the early gestational sac have
      corroborated anatomical studies showing that the first structures to appear are
      the celomic cavity and the secondary yolk sac. No single ultrasound measurement
      of the different anatomical features in the first trimester has been shown to
      have a high predictive value for determining early pregnancy outcome. Similarly,
      Doppler studies have failed to demonstrate abnormal blood flow indices in the
      first-trimester uteroplacental circulation of pregnancies that subsequently end
      in miscarriage. Ultrasound parameters combined with maternal serum hormone
      levels, maternal age, smoking habits, obstetric history and the occurrence of
      vaginal bleeding have all been combined in multivariate analyses, with mixed
      results. Combined ultrasound and in-vitro experiments have demonstrated that the
      maternal circulation inside the placenta starts at the periphery at around 9
      weeks of gestation and that this is associated with a physiological oxidative
      stress which could be the trigger for the formation of the placental membranes.
      Abnormal development of these membranes can result in subchorionic hemorrhage and
      threatened miscarriage with subsequent long-term consequences such as preterm
      rupture of the membranes and preterm labor, irrespective of the finding of a
      hematoma on ultrasound. In both euploid and aneuploid missed miscarriages there
      is clear ultrasound evidence for excessive entry of maternal blood at a very
      early stage inside the developing placenta resulting in oxidative stress and
      subsequent degeneration of villous tissue. The finding of blood flow in the
      intervillous space in cases of first-trimester miscarriage using color Doppler
      also appears to be useful in the prediction of success of expectant management.
      Miscarriages with blood flow within the intervillous space are up to four times
      more likely to complete with expectant management. TVS is considered the gold
      standard in the diagnosis and management of incomplete miscarriage. Expectant
      management of miscarriage, using ultrasound parameters to determine eligibility,
      could significantly reduce the number of unnecessary evacuations of the retained
      products of conception, depending on the criteria used.

PMID- 15861414
TI  - Temozolomide plus thalidomide in patients with brain metastases from melanoma: a
      phase II study.
AB  - BACKGROUND: Temozolomide plus thalidomide is a promising oral combination regimen
      for the treatment of metastatic melanoma. The current Phase II study examined the
      efficacy and safety of this combination in chemotherapy-naive patients with brain
      metastases. METHODS: Patients with histologically confirmed metastatic melanoma
      and measurable brain metastases received temozolomide (75 mg/m2 per day for 6
      weeks with a 2-week break between cycles) plus concomitant thalidomide (200
      mg/day escalating to 400 mg/day for patients < 70 years or 100 mg/day escalating
      to 250 mg/day for patients > or = 70 years). The primary end point was tumor
      response in the brain assessed every 8 weeks. RESULTS: Twenty-six patients with a
      median age of 60 years were treated. All patients had progressive brain
      metastases: 16 were symptomatic and 25 had extensive extracranial metastases.
      Eight patients had received whole-brain radiotherapy, 4 had received stereotactic
      radiotherapy, and 8 had received craniotomy with resection of hemorrhagic
      lesions. Fifteen patients completed > or = 1 cycle (median, 1 cycle; range, 0-4
      cycles), and 11 discontinued treatment before completing 1 cycle (7 for
      intracranial hemorrhage, 2 for pulmonary embolism, 1 for deep vein thrombosis,
      and 1 for Grade 3 rash). Of 15 patients assessable for response, 3 had a complete
      or partial response (12% intent to treat) and 7 had minor response or stable
      disease in the brain. However, 5 of these 10 patients had disease progression at
      extracranial sites. The median survival period was 5 months for all 26 patients
      and 6 months for the 15 assessable patients. CONCLUSIONS: Temozolomide plus
      thalidomide was an active oral regimen for patients with brain metastases from
      malignant melanoma.

PMID- 15861415
TI  - Outcome of fetal pleural effusions treated by thoracoamniotic shunting.
AB  - OBJECTIVE: Fetal pleural effusions are uncommon, and treatment options for
      moderate or severe effusions include drainage and thoracoamniotic shunting.
      However, relatively few records of effusions treated by thoracoamniotic shunting
      are available in the literature, so our objective was to study the outcome after
      thoracoamniotic shunting in our unit. METHODS: We searched the database of our
      tertiary fetal medicine unit for all cases of fetal pleural effusion treated by
      thoracoamniotic shunting between 1997 and 2003 inclusive, and studied the
      maternal and neonatal records. RESULTS: Ninety-two cases of fetal pleural
      effusion were studied, of which 21 had undergone a thoracoamniotic shunt. Sixteen
      of these 21 fetuses (76%) had associated hydrops, of which seven (44%) survived
      and, of the five (24%) without associated hydrops, three (60%) survived. There
      were two procedure-related losses. No shunted cases were associated with abnormal
      karyotype or proven maternal infection, but it is probable that three cases had
      been caused by an underlying genetic syndrome. CONCLUSION: The survival of
      fetuses with severe pleural effusions after thoracoamniotic shunting in this
      study was 48%.

PMID- 15861416
TI  - Urinary and rectal complications of contemporary permanent transperineal
      brachytherapy for prostate carcinoma with or without external beam radiation
      therapy.

PMID- 15861418
TI  - Metallic nanowires of Nb3Te4: a nanostructured chalcogenide.

PMID- 15861417
TI  - Nuclear factor kappa B activation is a potential target for preventing pancreatic
      carcinoma by aspirin.
AB  - BACKGROUND: Pancreatic carcinoma exhibits a unique genetic profile of mutations
      that may play key roles in its progression to malignant phenotypes. Constitutive
      activation of transcription factor nuclear factor kappa B (NF-kappaB) is a
      frequent molecular alteration in pancreatic carcinoma, suggesting a possible link
      between inflammation and cancer. The aims of the current study were to determine
      the effects of aspirin on pancreatic carcinoma prevention and to reveal a
      possible mechanism of aspirin-mediated cancer chemoprevention. METHODS: An
      orthotopic mouse model with human pancreatic carcinoma cell lines PANC-1, PANC
      1/Puro, and PANC-1/IkappaBalphaM was used to study the inhibitory effects of
      aspirin on pancreatic tumor formation. RESULTS: Aspirin inhibited constitutive NF
      kappaB activity in culture and, in turn, decreased the expression of the NF
      kappaB downstream target gene, Cox-2, in PANC-1 or PANC-1/Puro cells, without
      significantly inhibiting the in vitro growth of PANC-1/Puro cells. All animals
      inoculated with either PANC-1 or PANC-1/Puro cells, and not given aspirin,
      developed pancreatic tumors, whereas none of the mice injected with PANC
      1/IkappaBalphaM cells showed any evidence of pancreatic tumor formation. Animals
      given aspirin for 6 days before, or at the time of, orthotopic tumor cell
      injection showed a significantly lower incidence of tumor formation compared with
      those receiving aspirin 2 weeks after inoculation and controls receiving no
      aspirin. CONCLUSIONS: Aspirin repressed tumor formation by PANC-1 cells in vivo
      in a prophylactic setting, suggesting a possible mechanism for aspirin's
      preventive effect in pancreatic carcinoma through inhibition of NF-kappaB
      activation and a mechanistic link between inflammation and tumorigenesis. Aspirin
      mediated antiinflammatory approaches might be an effective strategy to prevent
      pancreatic carcinoma.

PMID- 15861419
TI  - F-81 skeleton from Wadi Mataha, Jordan, and its bearing on human variability in
      the Epipaleolithic of the Levant.
AB  - The discovery of a Middle Epipaleolithic adult skeleton (F-81) at the site of
      Wadi Mataha in southern Jordan provides new insights into human variability in
      the Epipaleolithic of the Levant. This paper analyzes the skeletal morphology of
      Wadi Mataha F-81 in the context of other Epipaleolithic remains from Jordan and
      Israel to assess the current evidence for morphological variability throughout
      this period. The F-81 skeleton shares morphological features with earlier
      Epipaleolithic skeletons from Ohalo and Nahal Ein Gev, and later Natufian
      populations. Despite the morphological similarities, F-81 extends the range of
      known variability prior to the Natufian with its unusually small stature and
      unique combination of morphological characteristics. High levels of cranial and
      postcranial robusticity suggest that the F-81 individual was physically active
      and terrestrially mobile. Pronounced bilateral asymmetry in the upper limb
      suggests significant lateralization of habitual activity. In the context of
      Epipaleolithic remains, the F-81 skeleton provides preliminary evidence for
      greater morphological variability, terrestrial mobility, and lateralized habitual
      behavior prior to the Natufian, and skeletal gracilization between the Middle and
      Late Epipaleolithic in the Levant.

PMID- 15861420
TI  - Knuckle-walking anteater: a convergence test of adaptation for purported knuckle
      walking features of African Hominidae.
AB  - Appeals to synapomorphic features of the wrist and hand in African apes, early
      hominins, and modern humans as evidence of knuckle-walking ancestry for the
      hominin lineage rely on accurate interpretations of those features as adaptations
      to knuckle-walking locomotion. Because Gorilla, Pan, and Homo share a relatively
      close common ancestor, the interpretation of such features is confounded somewhat
      by phylogeny. The study presented here examines the evolution of a similar
      locomotor regime in New World anteaters (order Xenarthra, family Myrmecophagidae)
      and uses the terrestrial giant anteater (Myrmecophaga tridactyla) as a
      convergence test of adaptation for purported knuckle-walking features of the
      Hominidae. During the stance phase of locomotion, Myrmecophaga transmits loads
      through flexed digits and a vertical manus, with hyperextension occurring at the
      metacarpophalangeal joints of the weight-bearing rays. This differs from the
      locomotion of smaller, arboreal anteaters of outgroup genera Tamandua and
      Cyclopes that employ extended wrist postures during above-branch quadrupedality.
      A number of features shared by Myrmecophaga and Pan and Gorilla facilitate load
      transmission or limit extension, thereby stabilizing the wrist and hand during
      knuckle-walking, and distinguish these taxa from their respective outgroups.
      These traits are a distally extended dorsal ridge of the distal radius, proximal
      expansion of the nonarticular surface of the dorsal capitate, a pronounced
      articular ridge on the dorsal aspects of the load-bearing metacarpal heads, and
      metacarpal heads that are wider dorsally than volarly. Only the proximal
      expansion of the nonarticular area of the dorsal capitate distinguishes knuckle
      walkers from digitigrade cercopithecids, but features shared with digitigrade
      primates might be adaptive to the use of a vertical manus of some sort in the
      stance phase of terrestrial locomotion. The appearance of capitate nonarticular
      expansion and the dorsal ridge of the distal radius in the hominin lineage might
      be indicative of a knuckle-walking ancestry for bipedal hominins if interpreted
      within the biomechanical and phylogenetic context of hominid locomotor evolution.

PMID- 15861421
TI  - The short die young: the interrelationship between stature and longevity-evidence
      from skeletal remains.
AB  - It has long been observed that tall people display longer life spans. The current
      data were employed to verify this association within the bioarchaeological
      context. To this end, stature and its association with age-at-death were analyzed
      in a pooled sample of 2,923 skeletons. Height was estimated from proxy indicators
      based on the maximum length of the humerus, radius, femur, and tibia. Stature
      estimation followed the procedure outlined by Pearson ([1899] Philos. Trans. R.
      Soc. Lond. [A] 192:169-244), incorporating minor modifications by Rosing ([ 1988]
      Handbuch der vergleichenden Biologie des Menschen; Stuttgart: Gustave Fischer, p
      586-600). Individual age estimates were classified into three mutually exclusive
      age groups: 20-39 years (591 males, 667 females), 40-59 years (876 males, 499
      females), and 60+ years (171 males, 119 females). The results document that both
      sexes display a statistically significant inverse relationship between adult
      height and age-at-death (males, P < 0.01; females, P < 0.05). Taking an
      epidemiological approach, the risk model implies that the estimated odds of
      survival beyond age 40 improve by approximately 16% for 1 SD in bone length.
      However, not all bones may be equally adept at displaying the association. The
      radius failed to support the positive association between stature and longevity,
      which may be indicative of a relatively greater contribution of environmental
      factor to radius length. Overall, the relationship between body height and
      longevity is not causal but coincidental: mitigated by diverse environmental
      factors such as nutrition, socioeconomic stressors, and disease load.

PMID- 15861422
TI  - Functional analysis of the gibbon foot during terrestrial bipedal walking:
      plantar pressure distributions and three-dimensional ground reaction forces.
AB  - This paper gives a detailed analysis of bipedal walking in the white-handed
      gibbon, based on collected pressure and force data. These data were obtained from
      four gibbons in the Wild Animal Park, Planckendael, Belgium, by using a walkway
      with integrated force plate and pressure mat. This is the first study that
      collects and describes dynamic plantar pressure data of bipedally walking
      gibbons, and combines these with force plate data. The combination of these data
      with previously described roll-off patterns of gibbons, based on general
      observations, video images, force plates, and EMG data, gives us a detailed
      description of foot function during gibbon bipedalism. In addition, we compare
      the observed characteristics of hylobatid bipedalism with the main
      characteristics of bonobo and human bipedalism. We found that gibbons are
      midfoot/heel plantigrade, and lack the typical heel-strike of other hominoids.
      The hallux is widely abducted and touches down at the onset of the stance phase,
      which results in an L-shaped course of the center of pressure. The vertical force
      curve is trapezoid to triangular in shape, with high peak values compared to
      humans. The braking component is shorter than the accelerating component, and
      shortens further at higher walking velocities. Speed has a significant influence
      on the forefoot peak pressures and on most of the defined gait parameters (e.g.,
      vertical force peak), and it alters the foot contact pattern as well. The
      investigation of existing form-function relationships in nonhuman primates is
      essential for the interpretation of fossil remains, and might help us understand
      the evolution of habitual bipedal walking in hominids.

PMID- 15861424
TI  - New approach to quantifying anatomical curvatures using high-resolution
      polynomial curve fitting (HR-PCF).

PMID- 15861426
TI  - Sexual dimorphism in modern human permanent teeth.
AB  - On average, males possess larger tooth crowns than females in contemporary human
      populations, although the degree of dimorphism varies within different
      populations. In previous studies, different amounts of either enamel or dentine
      were implicated as the cause of this dimorphism. In this study, we attempt to
      determine the nature of sexual dimorphism in the crowns of permanent modern human
      teeth and to determine if two contrasting tooth types (permanent third molars and
      canines) show identical patterns of dimorphism in enamel and dentine
      distribution. We estimated the relative contributions of both enamel and dentine
      to total crown size, from buccolingual sections of teeth. Our sample consisted of
      a total of 144 mandibular permanent third molars and 25 permanent mandibular
      canines of known sex. We show that sexual dimorphism is likely due, in part, to
      the presence of relatively more dentine in the crowns of male teeth. However,
      whatever the underlying cause, dimorphism in both tooth root and tooth crown size
      should produce measurable dimorphism in tooth weight, though this has not been
      previously explored. Therefore, we provide some preliminary data that indicate
      the usefulness of wet tooth weight as a measure of sexual dimorphism. Both male
      permanent third molars and canines are significantly heavier than those of
      females. The weight dimorphism reported here for both classes of teeth may prove
      a useful finding for future forensic studies. In particular, weights of canines
      may be more useful as a means of sexing modern human skeletal material than
      linear or area measurements of teeth.

PMID- 15861427
TI  - Geometric morphometric analysis of mandibular ramus flexure.
AB  - Many characteristics of the human skeleton can only be assessed morphologically,
      which may be problematic due to factors such as interobserver error and
      difficulties with standardization. Flexure of the mandibular ramus is one of
      these traits, and various researchers found widely differing results using this
      morphological feature. The aim of this study was to determine whether differences
      between male and female mandibular rami could be observed using the computerized
      method of geometric morphometrics, a valuable tool that helps quantify shape
      differences. Twenty-eight mandibular rami of black females and 43 of black males
      were photographed in a standard plane and assessed. It was found that the females
      were more scattered on the graph (more variable in shape), while the males
      clustered more around the center point where the two axes met (shape more
      constant). There was, however, considerable overlap between the sexes. Although
      different tendencies exist between the rami of males (being more flexed) and
      females (tending to be straight), the extent of these differences is not adequate
      to predict the sex of a single individual.

PMID- 15861428
TI  - Analysis of morphologic patterns of fine-needle aspiration of the breast to
      reduce false-negative results in breast cytology.
AB  - BACKGROUND: The identification of specific morphologic diagnostic criteria is of
      paramount importance to optimize the accuracy of fine-needle aspiration cytology
      (FNAC) and to reduce the rate of false-negative results. In the current study,
      the authors reviewed a consecutive series of false-negative findings observed in
      the study center to define the presence and degree of cytologic abnormalities.
      False-negative cases were randomly mixed with true-negative cases and were
      reviewed by a panel of expert readers in a blinded fashion. The main objective of
      the current study was to identify a morphologic pattern that may permit the
      reduction of false-negative findings while maintaining the specificity of FNAC.
      METHODS: A blind review of a set of 41 consecutive false-negative and 49 true
      negative breast aspiration samples was performed by a panel of 10 expert
      cytologists who were asked to give a final report and to classify the samples
      according to classic morphologic parameters. RESULTS: The majority final report
      sensitivity was 54% (range, 19-61%) and specificity was 73% (range, 65-92%). The
      average concordance with the majority report, adjusted for chance agreement
      (kappa statistic), was moderate at 0.54 (range, 0.40-0.65). Enlarged nuclear
      size, a hyperchromatic nucleus, the absence of naked nuclei, and the absence of
      apocrine metaplasia were reported more frequently in carcinoma cases, although
      not to a significant extent. The only variable found to be associated
      significantly (P = 0.041) with a diagnosis of carcinoma was the presence of
      microcalcifications, which nevertheless were found to occur in only a minority of
      carcinoma cases (7 of 41 cases) or controls (2 of 49 controls). Multivariate
      analysis demonstrated that the presence of microcalcifications (odds ration [OR]
      of 3.0; 95% confidence interval [95% CI], 1.2-7.4), the absence of naked nuclei
      (OR of 2.4; 95% CI, 1.3-4.4), and enlargement of the nucleus (OR of 1.9; 95% CI,
      1.1-3.4) were all independently associated with false-negative findings.
      Diagnostic accuracy using a morphology-based score did not appear to improve the
      results substantially compared with the final report (sensitivity of 0.46 vs.
      0.54 [P = 0.508] and a specificity of 0.80 vs. 0.73 [P = 0.218]). CONCLUSIONS:
      The results of the current study confirm that breast FNAC false-negative results
      are at least partially the result of underreporting of abnormalities that may be
      noted at review. Detailed analysis of a single morphologic characteristic was
      found to be of limited diagnostic value, suggesting that operators do perceive
      abnormalities but cannot translate these findings into distinct morphologic
      categories.

PMID- 15861429
TI  - Linear enamel hypoplasias as indicators of systemic physiological stress:
      evidence from two known age-at-death and sex populations from postmedieval
      London.
AB  - Enamel hypoplasias are useful indicators of systemic growth disturbances during
      childhood, and are routinely used to investigate patterns of morbidity and
      mortality in past populations. This study examined the pattern of linear enamel
      hypoplasias in two different burial populations from 18th and 19th Century church
      crypts in London. Linear enamel hypoplasias on the permanent dentitions of
      individuals from the crypt of Christ Church, Spitalfields, were compared to
      enamel defects on the teeth of individuals from St. Bride's. The method used
      involves the identification of enamel defects at a microscopic level, and
      systemic perturbations are detected by matching hypoplasias among different tooth
      classes within each individual. The pattern of linear enamel hypoplasias was
      contrasted between individuals from the burial sites of Spitalfields and St.
      Bride's, between males and females, and between those aged less than 20 years of
      age and those aged over 20 years at death. Six different parameters were
      examined: frequency of linear enamel hypoplasias, interval between defects,
      duration of hypoplasias, age at first occurrence of hypoplasia, age at last
      occurrence of hypoplasia, and the percentage of enamel formation time taken up by
      growth disturbances. All individuals in the study displayed linear enamel
      hypoplasias, with up to 33% of total visible enamel formation time affected by
      growth disruptions. Multiple regression analysis indicated a number of
      significant differences in the pattern of enamel hypoplasias. Individuals from
      Spitalfields had shorter intervals between defects and greater percentages of
      enamel formation time affected by growth disturbances than did individuals from
      St. Bride's. Females had greater numbers of linear enamel hypoplasias, shorter
      intervals between defects, and greater percentages of enamel formation time
      affected by growth disturbances than males. There were also differences in the
      pattern of enamel hypoplasias and age at death in this study. Individuals who
      died younger in life had an earlier age at first occurrence of enamel hypoplasia
      than those who survived to an older age. The pattern of enamel hypoplasias
      detected in this study was influenced by tooth crown geometry and tooth wear such
      that most defects were found in the midcrown and cervical regions of the teeth,
      and greater numbers of defects were identified on the anterior teeth. Differences
      in sensitivity of the parameters used for the detection of enamel hypoplasias
      were found in this study. The percentage of visible enamel formation time
      affected by growth disturbances was the parameter that identified the greatest
      number of significant differences among the subgroups examined.

PMID- 15861430
TI  - On the in vitro and in vivo properties of four locked nucleic acid nucleotides
      incorporated into an anti-H-Ras antisense oligonucleotide.
AB  - Locked nucleic acid (beta-D-LNA) monomers are conformationally restricted
      nucleotides bearing a methylene 2'-O, 4'-C linkage that have an unprecedented
      high affinity for matching DNA or RNA. In this study, we compared the in vitro
      and in vivo properties of four different LNAs, beta-D-amino LNA (amino-LNA), beta
      D-thio LNA (thio-LNA), beta-D-LNA (LNA), and its stereoisomer alpha-L-LNA in an
      antisense oligonucleotide (ODN). A well-known antisense ODN design against H-Ras
      was modified at the 5'- and 3'-ends with the different LNA analogues (LNA-DNA-LNA
      gapmer design). The resulting gapmers were tested in cancer-cell cultures and in
      a nude-mouse model bearing prostate tumor xenografts. The efficacy in target
      knockdown, the biodistribution, and the ability to inhibit tumor growth were
      measured. All anti H-Ras ODNs were very efficient in H-Ras mRNA knockdown in
      vitro, reaching maximum effect at concentrations below 5 nM. Moreover, the anti-H
      Ras ODN containing alpha-L-LNA had clearly the highest efficacy in H-Ras
      knockdown. All LNA types displayed a great stability in serum. ODNs containing
      amino-LNA showed an increased uptake by heart, liver, and lungs as compared to
      the other LNA types. Both alpha-L-LNA and LNA gapmer ODNs had a high efficacy of
      tumor-growth inhibition and were nontoxic at the tested dosages. Remarkably, in
      vivo tumor-growth inhibition could be observed at dosages as low as 0.5 mg kg(-1)
      per day. These results indicate that alpha-L-LNA is a very promising member of
      the family of LNA analogues in antisense applications.

PMID- 15861431
TI  - Activation of CREB by tauroursodeoxycholic acid protects cholangiocytes from
      apoptosis induced by mTOR inhibition.
AB  - Tauroursodeoxycholic acid (TUDCA) is a cytoprotective bile acid frequently
      prescribed to patients with cholestatic diseases. Several mechanisms of action
      have been investigated, but the possibility that cyclic adenosine monophosphate
      responsive element binding protein (CREB), a transcription factor promoting cell
      survival, mediates TUDCA's protective effects has not been considered. We
      examined whether TUDCA activates CREB and whether this activation can protect
      biliary epithelial cells. Cholangiocytes were stressed by exposure to CCI-779,
      which inhibits signaling though the kinase mTOR (mammalian target of rapamycin),
      resulting in cell cycle arrest and apoptosis. Incubation of normal rat
      cholangiocytes (NRC) cells, with TUDCA resulted in phosphorylation of CREB
      (Western blotting analysis) and activation of CREB transcription activity
      (luciferase reporter assay). Inhibition of calcium signals and inhibition of
      protein kinase C prevented the TUDCA-induced activation of CREB. CCI-779
      decreased the viability of rat cholangiocytes in a dose-dependent manner (MTT [3
      (4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay). TUDCA
      protected against CCI-779 cytotoxicity. A dominant negative form of CREB was
      stably transduced in NRC cells (NRC-M1). TUDCA protection was decreased in NRC
      M1. While CCI-779 induced apoptosis in NRC cells as determined by caspase 3
      activity, TUDCA attenuated CCI-779-induced apoptosis, an effect absent in NRC-M1.
      Finally, CCI-779 blocked proliferation of both NRC and NRC-M1 (thymidine
      incorporation) and this was unaffected by TUDCA. In conclusion, TUDCA activates
      CREB in cholangiocytes, reducing the apoptotic effect of CCI-779. These findings
      suggest a novel cytoprotective mechanism for this bile acid.

PMID- 15861432
TI  - Biosynthetic precursors of fungal pyrrolizidines, the loline alkaloids.
AB  - Loline alkaloids are saturated pyrrolizidines with a substituted 1-amino group
      and an oxygen bridge between C2 and C7, and are insecticidal metabolites of plant
      symbiotic fungi (endophytes). Cultures of the endophyte, Neotyphodium uncinatum,
      incorporated labeled L-proline and L-homoserine into the 1-aminopyrrolizidine, N
      formylloline. The A-ring carbons C1-C3 and the N1 were derived from L-homoserine;
      the B-ring carbons C5-C8 and the ring nitrogen were derived from L-proline.
      Incorporation of both deuterium atoms from L-[4,4-(2H2)]homoserine and feeding
      tests with labeled L-methionine indicated that L-homoserine incorporation was not
      achieved via aspartyl semialdehyde or S-adenosylmethionine, but probably involved
      a highly novel N--C bond-forming gamma-substitution reaction.

PMID- 15861433
TI  - Annonaceous acetogenins: the hydroxyl groups and THF rings are crucial structural
      elements for targeting the mitochondria, demonstration with the synthesis of
      fluorescent squamocin analogues.

PMID- 15861434
TI  - New methods for the generation of carbohydrate arrays on glass slides and their
      evaluation.
AB  - Glycosides, having spacers functionalized with an aldehyde or a carboxylic group,
      were immobilized through reductive amination or amidation, respectively, onto
      amino-functionalized glass slides. Hybridization experiments with lectins
      exhibited very little nonspecific protein binding, hence precluding the necessity
      for the blocking of unreacted functional groups on the glass slide. The covalency
      and the concentration dependency of the sugar ligation to the glass slide were
      demonstrated; the reversibility and the selectivity of lectin-carbohydrate
      interactions were shown.

PMID- 15861435
TI  - Organometallic chemistry inside the pore walls of mesostructured silica
      materials.

PMID- 15861436
TI  - Regio- and stereoselective approach to 1,2-di- and 1,1,2-trisilylethenes by
      cobalt-mediated reaction of silyl-substituted dibromomethanes with
      silylmethylmagnesium reagents.

PMID- 15861437
TI  - DNA microarrays as decoding tools in combinatorial chemistry and chemical
      biology.

PMID- 15861438
TI  - Catalytic enantioselective total syntheses of bisorbicillinolide,
      bisorbicillinol, and bisorbibutenolide.

PMID- 15861439
TI  - Total synthesis of 2-(5,6-epoxyisoprostane A2)phosphorylcholine and elucidation
      of the relative configuration of the isoprostane moiety.

PMID- 15861440
TI  - Enantioselective formation of stereogenic carbon-fluorine centers by a simple
      catalytic method.

PMID- 15861441
TI  - Non-C2-symmetric, chirally economical, and readily tunable linked-binols: design
      and application in a direct catalytic asymmetric mannich-type reaction.

PMID- 15861442
TI  - Environmentally stable super water-repellent poly(alkylpyrrole) films.

PMID- 15861444
TI  - Effective cobalt mediation of the radical polymerization of vinyl acetate in
      suspension.

PMID- 15861443
TI  - Quadruple deprotonation of 2-aminophenylphosphane with a p-block-metal/alkali
      metal base.

PMID- 15861445
TI  - Asymmetric spin density distribution in the copper(II) complex of N-confused
      tetraphenylporphyrin: a multifrequency continuous-wave and pulse EPR study.

PMID- 15861446
TI  - Biomimetic synthesis of grossularines-1.

PMID- 15861447
TI  - Evidence that electrostatic interactions dictate the ligand-induced arrest of RNA
      global flexibility.

PMID- 15861448
TI  - Dynamic effects on [3,3] and [1,3] shifts of 6-methylenebicyclo[3.2.0]hept-2-ene.

PMID- 15861449
TI  - Simultaneous observation of green multiphoton upconversion and red and blue NLO
      processes from polymeric terbium(III) complexes.

PMID- 15861450
TI  - Synthesis of luciferyl coenzyme A: a bioluminescent substrate for firefly
      luciferase in the presence of AMP.

PMID- 15861451
TI  - Introduction of multiple elements of chirality around an aromatic core and an
      approach to enantiomerically pure C3-symmetric ligands.

PMID- 15861452
TI  - AFM-tip-integrated amperometric microbiosensors: high-resolution imaging of
      membrane transport.

PMID- 15861453
TI  - Heterotrimetallic RuMnMn species on a hydrotalcite surface as highly efficient
      heterogeneous catalysts for liquid-phase oxidation of alcohols with molecular
      oxygen.

PMID- 15861454
TI  - Cellulose: fascinating biopolymer and sustainable raw material.
AB  - As the most important skeletal component in plants, the polysaccharide cellulose
      is an almost inexhaustible polymeric raw material with fascinating structure and
      properties. Formed by the repeated connection of D-glucose building blocks, the
      highly functionalized, linear stiff-chain homopolymer is characterized by its
      hydrophilicity, chirality, biodegradability, broad chemical modifying capacity,
      and its formation of versatile semicrystalline fiber morphologies. In view of the
      considerable increase in interdisciplinary cellulose research and product
      development over the past decade worldwide, this paper assembles the current
      knowledge in the structure and chemistry of cellulose, and in the development of
      innovative cellulose esters and ethers for coatings, films, membranes, building
      materials, drilling techniques, pharmaceuticals, and foodstuffs. New frontiers,
      including environmentally friendly cellulose fiber technologies, bacterial
      cellulose biomaterials, and in-vitro syntheses of cellulose are highlighted
      together with future aims, strategies, and perspectives of cellulose research and
      its applications.

PMID- 15861455
TI  - Magnetic moments of the endohedral cluster fullerenes Ho3N@C80 and Tb3N@C80: the
      role of ligand fields.

PMID- 15861456
TI  - Microzonal projection and climbing fiber remodeling in single olivocerebellar
      axons of newborn rats at postnatal days 4-7.
AB  - An adult olivocerebellar axon ramifies into about seven climbing fibers that
      innervate single Purkinje cells arranged in a longitudinal microzone. To clarify
      the developmental basis of this projection, individual olivocerebellar axons were
      labeled with biotinylated dextran amine injected into the inferior olive in rats
      at postnatal days 4-7. The entire trajectories of single olivocerebellar axons
      and single terminal arbors of climbing fibers were reconstructed from serial
      sections of the cerebellum and medulla. Single axons ramified into climbing
      fibers that terminated in a narrow band-shaped area comparable to the adult
      microzone. This indicated that olivocerebellar microzones are predetermined.
      Terminal arbors of climbing fibers were remodeled from loose creeper type,
      through intermediate transitional type, into dense nest type. Each
      olivocerebellar axon had some 100 nascent climbing fibers in the creeper stage,
      whereas each axon had about 10 climbing fibers and about as many atrophic
      climbing fibers in the nest stage. This decrease indicated that overabundant
      nascent climbing fibers degenerate concomitantly with the remodeling of remaining
      climbing fibers. Atrophic terminal arbors and non-climbing fiber thin collaterals
      were considered the intermediate forms of degenerating climbing fibers. This
      remodeling and degeneration of climbing fibers may be related to the
      electrophysiological regression of climbing fiber-Purkinje cell synapses. The
      remodeling of climbing fibers occurred earliest in lobules VIII (caudal part) and
      IXa-b, and then in lobules IXc and X. The more developed granular layer in these
      areas compared to other areas suggests that the cortical environment triggers
      climbing fiber remodeling.

PMID- 15861457
TI  - Expression profile analysis within the human hippocampus: comparison of CA1 and
      CA3 pyramidal neurons.
AB  - The hippocampus contains several distinct cell types that are interconnected by a
      well-characterized series of synaptic circuits. To evaluate molecular and
      cellular signatures of individual cell types within the normal adult human
      hippocampal formation, expression profile analysis was performed on individual
      CA1 and CA3 pyramidal neurons using a novel single cell RNA amplification
      methodology coupled with custom-designed cDNA array analysis. Populations of CA1
      and CA3 neurons were also compared with regional dissections of the hippocampus
      from the same tissue sections. Molecular fingerprint comparison of cresyl violet
      stained CA1 and CA3 pyramidal neurons microaspirated from the hippocampus of
      normal control subjects indicated significant differences in relative expression
      levels for approximately 16% (20 of 125) genes evaluated on the custom-designed
      cDNA array platform. Significant differences were observed for several
      transcripts relevant to the structure and function of hippocampal neurons,
      including specific glutamate receptors, gamma-aminobutyric acid (GABA) A
      receptors, cytoskeletal elements, dopamine receptors, and immediate-early genes.
      Compared with the regional assessment of gene expression, both CA1 and CA3
      neurons displayed a relative enrichment of classes of transcripts that included
      glutamate receptors, transporters, and interacting proteins, GABA receptors and
      transporters, synaptic-related markers, and catecholamine receptors and
      transporters. In contrast, the regional hippocampal dissection had an increased
      level of gene expression for cytoskeletal elements as well as glial-associated
      markers. Expression profile analysis illustrates the importance of evaluating
      individual cellular populations within a functional circuit and may help define
      elements that confer unique properties to individual populations of hippocampal
      neurons under normal and diseased conditions.

PMID- 15861458
TI  - Homer expression in the Xenopus tadpole nervous system.
AB  - Homer proteins are integral components of the postsynaptic density and are
      thought to function in synaptogenesis and plasticity. In addition, overexpression
      of Homer in the developing Xenopus retinotectal system results in axonal
      pathfinding errors. Here we report that Xenopus contains the homer1 gene,
      expressed as the isoform, xhomer1b, which is highly homologous to the mammalian
      homer1b. The mammalian homer1 gene is expressed as three isoforms, the truncated
      or short form homer1a and the long forms homer1b and -1c. For Xenopus, we cloned
      three very similar variants of homer1b, identified as Xenopus xhomer1b.1,
      xhomer1b.2, and xhomer1b.3, which display up to 98% homology with each other and
      90% similarity to mammalian homer1b. Furthermore, we demonstrate that Xenopus
      also contains a truncated form of the Homer1 protein, which could be induced by
      kainic acid injection and is likely homologous to the mammalian Homer1a. xHomer1b
      expression was unaffected by neuronal activity levels but was developmentally
      regulated. Within the brain, the spatial and temporal distributions of both Homer
      isoforms were similar in the neuropil and cell body regions. Homer1 was detected
      in motor axons. Differential distribution of the two isoforms was apparent:
      Homer1b immunoreactivity was prominent at junctions between soma and the
      ventricular surface; in the retina, the Mueller radial glia were immunoreactive
      for Homer1, but not Homer1b, suggesting the retinal glia contain only the Homer1a
      isoform. Homer1b expression in muscle was prominent throughout development and
      was aligned with the actin striations in skeletal muscle. The high level of
      conservation of the xhomer1 gene and the protein expression in the developing
      nervous system suggest that Homer1 expression may be important for normal
      neuronal circuit development.

PMID- 15861460
TI  - Localization of the three GnRH types and GnRH receptors in the brain of a cichlid
      fish: Insights into their neuroendocrine and neuromodulator functions.
AB  - The cognate receptor for any of the known gonadotropin-releasing hormones (GnRHs)
      has not been directly demonstrated. In order to establish this and shed light on
      the functions of GnRH types, we analyzed the neuroanatomical location and time of
      initial expression of three distinct GnRH receptors (GnRH-Rs) and the three
      endogenous GnRHs in the brain of developing and sexually mature tilapia
      Oreochromis niloticus using immunocytochemistry. In all age groups, including
      males and females, GnRH-RIA was seen specifically in gonadotropes (Parhar et al.
      [2002] J Neuroendocrinol 14:657-665) but was undetectable in the brain. On day 8
      after fertilization, GnRH-RIB was first seen in the periventricular hypothalamus
      (lateral recess nucleus, posterior recess nucleus, posterior tuberal nucleus) and
      GnRH-RIII in the olfactory epithelium, olfactory bulb, telencephalon, preoptic
      region, mediobasal hypothalamus, thalamus, mesencephalon, and in the hindbrain.
      Double-label immunocytochemistry showed GnRH1 (Ser(8) GnRH)-immunoreactive
      neuronal processes projecting mainly to the proximal pars distalis of the
      pituitary, while GnRH2 (His(5), Trp(7), Tyr(8) GnRH) and GnRH3 (Trp(7), Leu(8)
      GnRH) fibers were observed in close association with cells containing GnRH-RIB
      and GnRH-RIII in the brain. These results suggest that GnRH-RIA might be
      hypophysiotropic in nature, whereas GnRH-RIB and GnRH-RIII could have additional
      neuromodulatory functions. Further, evidence of close proximity of GnRH-R
      containing cells and neuronal processes of multiple GnRH types suggests complex
      cross-talk between several GnRH ligands and GnRH-Rs.

PMID- 15861461
TI  - Distribution of galanin-like immunoreactivity in the brain of the Siberian
      sturgeon (Acipenser baeri).
AB  - Galanin is a 29-amino acid peptide widely distributed in the central nervous
      system of vertebrates. The organization of galaninergic systems is well known in
      teleosts, the most advanced actinopterygians, but no data are available on
      primitive bony fish. To extend the evolutionary analysis of galaninergic systems
      we studied the distribution of galanin-like immunoreactive (GAL-ir) cells and
      fibers in the sturgeon brain, since chondrosteans are among the most primitive
      extant actinopterygians. Double-immunolabeling experiments were performed to
      compare the distribution of galanin with that of neurophysin, tyrosine
      hydroxylase, and serotonin. Numerous GAL-ir cells of cerebrospinal fluid
      contacting (CSF-C) type were found in the ventral telencephalon, preoptic area,
      and in the tuberal and caudal hypothalamus. The distribution of GAL-ir elements
      in the sturgeon brain shows many similarities to that observed in other
      vertebrates, but also important differences, such as the abundance of GAL-ir CSF
      C cells, which appear to be a primitive characteristic. GAL-ir neurons observed
      in the sturgeon telencephalic hemispheres perhaps represent the basic
      organization of common ancestors of bony fishes and tetrapods. In the preoptic
      hypophyseal system, GAL-ir cells appeared to be related not only with neurophysin
      expressing neurons (in the tuberal hypothalamus) but also with serotoninergic and
      catecholamines-synthesizing neurons (in preoptic and tuberal nuclei). Numerous
      GAL-ir fibers were observed in the median eminence and neural lobe of the
      hypophysis, indicating that galanin may play a role in the modulation of
      hypophyseal secretion. GAL-ir neurons were absent from the sturgeon brainstem,
      suggesting that their presence in other vertebrates could represent an
      evolutionary recent acquisition.

PMID- 15861459
TI  - Species and sex differences in brain distribution of corticotropin-releasing
      factor receptor subtypes 1 and 2 in monogamous and promiscuous vole species.
AB  - Corticotropin-releasing factor (CRF) receptor subtypes 1 and 2 have been
      implicated in rodent models of anxiety, but much less is known about the CRF
      system and social behavior. Both corticosterone and central CRF receptors
      modulate pair bonding in the monogamous prairie vole. Using receptor
      autoradiography, we mapped CRFR(1) and CRFR(2) in the brains of two monogamous
      vole species, the prairie vole and pine vole, and two promiscuous vole species,
      the meadow vole and montane vole. We found markedly different patterns of brain
      CRFR(1) and CRFR(2) binding among the four species, including species differences
      in the olfactory bulb, nucleus accumbens, lateral septum, hippocampus,
      laterodorsal thalamus, cingulate cortex, superior colliculus, and dorsal raphe.
      Interestingly, we also observed striking sex differences in voles: CRFR(2)
      binding was higher in the encapsulated bed nucleus of the stria terminalis in
      males than females for all four vole species. These results suggest possible
      sites of action for CRF-induced facilitation of pair bond formation in prairie
      voles, as well as potential sex differences in the CRF modulation of pair
      bonding. Further examination of CRF receptors in vole species may reveal a novel
      role for CRF in social behavior. Ultimately, our results identify several brain
      regions with conserved CRF receptor patterns across rodent and primate species,
      in contrast to several brain regions with phylogenetically plastic CRF receptor
      patterns, and have interesting implications for the evolution of CRF receptor
      patterns and behavior.

PMID- 15861462
TI  - Immunolocalization of Bex protein in the mouse brain and olfactory system.
AB  - Bex proteins are expressed from a family of "brain expressed X-linked genes" that
      are closely linked on the X-chromosome. Bex1 and 2 have been characterized as
      interacting partners of the olfactory marker protein (OMP). Here we report the
      distribution of Bex1 and Bex2 mRNAs in several brain regions and the development
      and characterization of an antibody to mouse Bex1 protein that cross-reacts with
      Bex2 (but not Bex3), and its use to determine the cellular distribution of Bex
      proteins in the murine brain. The specificity of the antiserum was characterized
      by immunoprecipitation and Western blots of tissue and transfected cell extracts
      and by immunocytochemical analyses of cells transfected with either Bex1 or Bex2.
      Antibodies preabsorbed with Bex2 still recognize Bex1, while blocking with Bex1
      eliminates all immunoreactivity to both Bex1 and Bex2. Bex immunoreactivity (ir)
      was primarily localized to neuronal cells within several regions of the brain,
      including the olfactory epithelium, bulb, peri/paraventricular nuclei,
      suprachiasmatic nucleus, arcuate nucleus, median eminence, lateral hypothalamic
      area, thalamus, hippocampus, and cerebellum. RT-PCR and in situ hybridization
      demonstrated the presence of Bex mRNA in several of these regions. Double-label
      immunocytochemistry indicates that Bex-ir is colocalized with OMP in mature
      olfactory receptor neurons (ORNs) and in the OMP-positive subpopulation of
      neurons in hypothalamus. This is the first anatomical mapping of Bex proteins in
      the mouse brain and their colocalization with OMP in ORNs and hypothalamus.

PMID- 15861463
TI  - Distribution and abundance of metabotropic glutamate receptor subtype 2 in rat
      brain revealed by [3H]LY354740 binding in vitro and quantitative radioautography:
      correlation with the sites of synthesis, expression, and agonist stimulation of
      [35S]GTPgammas binding.
AB  - Until recently, there was a lack of selective radioligands for the subtypes of
      metabotropic glutamate (mGlu) receptors. [(3)H]LY354740 ((+)-2
      aminobicyclo[3,1,0]hexane-2,6-dicarboxylic acid), a selective agonist for group
      II receptors (mGlu2 and -3, which are negatively coupled to cAMP production), has
      now been used to map their brain distribution and abundance by in vitro binding
      and quantitative radioautography. The selective cation dependence of its binding
      allowed the discrimination between mGlu2 and mGlu3 receptor labeling. Thus, in
      the presence of Ca(2+) and Mg(2+) ions, the agonist bound selectively to mGlu2
      receptors as evidenced by: 1) the correlative distribution and abundance of
      binding sites (highest in the lacunosum moleculare of the hippocampus and lowest
      in white matter) with mGlu2 receptor mRNA and protein revealed by in situ
      hybridization histochemistry and immunohistochemistry, respectively; 2) its
      selective pharmacology; and 3) the distribution of LY354740-stimulated
      [(35)S]GTPgammaS binding (25-97% above basal, according to the brain region),
      revealing G protein-coupled receptor coupling to G(i) proteins. Nonspecific
      binding (in the presence of 10 muM DCG-IV, a group II-selective, mGlu2
      preferring, receptor agonist) was <10% of total. In adjacent sections, the
      distribution of binding sites for [(3)H]DCG-IV was very similar. This extensive
      study paves the way for investigations of the regional expression and regulation
      of mGlu2 receptors in human CNS diseases, such as Alzheimer's disease, which may
      reveal their functional roles and identify potential therapeutic drug targets.
      Indeed, it has recently been demonstrated (Higgins et al. [2004]
      Neuropharmacology 46:907-917) that pharmacological manipulation of mGlu2
      receptors influences cognitive performance in the rodent.

PMID- 15861464
TI  - Low-temperature bath/coupled-capillary/sweeping-micellar electrokinetic capillary
      chromatography for the separation of naphthalene-2,3-dicarboxaldehyde-derivatized
      dopamine and norepinephrine.
AB  - The use of a low-temperature (0 degrees C) bath-assisted coupled capillary for
      the separation of naphthalene-2,3-dicarboxaldehyde (NDA)-derivatized dopamine and
      norepinephrine using the sweeping-micellar electrokinetic capillary
      chromatography (MEKC) mode is described. In this technique, a capillary
      consisting of two portions with different inside diameters is used. Therefore,
      the field strength inside the capillary is different. Hence, the electrophoretic
      migration velocities of the analytes and the electro-osmotic flow (EOF) also are
      different. Furthermore, when a portion of the capillary (wide portion, used for
      sweeping) is immersed in a low-temperature bath, the viscosity of the buffer and
      the retention factor of the analytes inside are increased. Thus, not only are the
      interactions between the SDS micelles and the analytes increased, but the SDS
      analytes also move more slowly. As a result, a more complete separation can be
      achieved, even when the sample injection volume is large, up to approximately 2
      microL. In general, when the volume of an injected sample is larger, the effects
      of sweeping and separation would become insufficient, especially when the
      retention values (k) of the analytes are quite different. However, this
      limitation can be improved when the low-temperature bath/coupled
      capillary/sweeping-MEKC mode is used.

PMID- 15861465
TI  - Free-flow isoelectric focusing of proteins remaining in cell fragments following
      sonication of thyroid carcinoma cells.
AB  - The method of preparing protein mixtures for electrophoretic analysis of membrane
      associated cell proteins was improved. By sonication, about one-half of the
      proteins of thyroid cells were released into the supernatant, while the other
      half preferentially comprising membrane proteins still remained in cell
      fragments, which could be sedimented by centrifugation. After sonication, even
      those proteins which remained in cell fragments, could completely be dissolved by
      free-flow isoelectric focusing media. They migrated through the free-flow
      electrophoresis chamber without forming precipitates. Because of these
      improvements, it was possible to show that the two thyroid cancer cell lines ML-1
      and ONCO-DG1 express cytokeratin 8 at similar rates, but cytokeratins 7 and 18
      differently. In addition, the presence of inorganic pyrophosphatase, tubulin-beta
      5, and tubulin-beta-1 chains in human thyroid cells was proved for the first
      time.

PMID- 15861466
TI  - Temperature measurements in microfluidic systems: heat dissipation of negative
      dielectrophoresis barriers.
AB  - The manipulation of living biological cells in microfluidic channels by a
      combination of negative dielectrophoretic barriers and pressure-driven flows is
      widely employed in lab-on-a-chip systems. However, electric fields in conducting
      media induce Joule heating. This study investigates if the local temperatures
      reached under typical experimental conditions in miniaturized systems cause a
      potential risk for hyperthermic stress or cell damage. Two methods of optical in
      situ temperature detection have been tested and compared: (i) the exposure of the
      thermo-dependent fluorescent dye Rhodamine B to heat sources situated in
      microfluidic channels, and (ii) the use of thermoprecipitating N-alkyl
      substituted acrylamide polymers as temperature threshold probes. Two-dimensional
      images of temperature distributions in the vicinity of active negative
      dielectrophoresis (nDEP)-barriers have been obtained and local temperature
      variations of more than 20 degrees C have been observed at the electrode edges.
      Heat propagation via both buffer and channel walls lead to significant
      temperature increases within a perimeter of 100 microm and more. These data
      indicate that power dissipation has to be taken into account when experiments at
      physiological temperatures are planned.

PMID- 15861467
TI  - Microchip electrophoretic protein separation using electroosmotic flow induced by
      dynamic sodium dodecyl sulfate-coating of uncoated plastic chips.
AB  - Separation of sodium dodecyl sulfate (SDS)-protein complexes is difficult on
      plastic microchips due to protein adsorption onto the wall. In this paper, we
      elucidated the reasons for the difficulties in separating SDS-protein complexes
      on plastic microchips, and we then demonstrated an effective method for
      separating proteins using polymethyl methacrylate (PMMA) microchips. Separation
      difficulties were found to be dependent on adsorption of SDS onto the hydrophobic
      surface of the channel, by which cathodic electroosmotic flow (EOF; reversed
      flow) was generated. Our developed method effectively utilized the reversed flow
      from this cathodic EOF as a driving force for sample proteins using permanently
      uncoated but dynamic SDS-coated PMMA microchips. High-speed (6 s) separation of
      proteins and peptides up to 116 kDa was successfully achieved using this system.

PMID- 15861468
TI  - Rapid separation of protein isoforms by capillary zone electrophoresis with new
      dynamic coatings.
AB  - Many cellular functions are regulated through protein isoforms. Changes in the
      expression level or regulatory dysfunctions of isoforms often lead to
      developmental or pathological disorders. Isoforms are traditionally analyzed
      using techniques such as gel- or capillary-based isoelectric focusing. However,
      with proper electro-osmotic flow (EOF) control, isoforms with small pI
      differences can also be analyzed using capillary zone electrophoresis (CZE). Here
      we demonstrate the ability to quickly resolve isoforms of three model proteins
      (bovine serum albumin, transferrin, alpha1-antitrypsin) in capillaries coated
      with novel dynamic coatings. The coatings allow reproducible EOF modulation in
      the cathodal direction to a level of 10(-9) m2V(-1)s(-1). They also appear to
      inhibit protein adsorption to the capillary wall, making the isoform separations
      highly reproducible both in peak areas and apparent mobility. Isoforms of
      transferrin and alpha1-antitrypsin have been implicated in several human
      diseases. By coupling the CZE isoform separation with standard affinity capture
      assays, it may be possible to develop a cost-effective analytical platform for
      clinical diagnostics.

PMID- 15861469
TI  - Hydrodynamic radius ladders of proteins.
AB  - We introduce hydrodynamic radius ladders of proteins as a new tool to isolate and
      measure the role of hydrodynamic size on transport properties of proteins. Radius
      ladders are collections of derivatives of a protein that differ incrementally in
      number of polyethylene glycol (PEG) chains grafted to their surface. The addition
      of these chains causes the hydrodynamic size of the protein to increase.
      Capillary electrophoresis (CE) separates these derivatives into individual peaks
      or "rungs" of a ladder composed of proteins that have the same number of PEG
      chains, and provides a way to measure the values of hydrodynamic radius of
      proteins that constitute the rungs of the ladder. We demonstrate the utility of
      this approach by measuring the partitioning of radius ladders into polymer
      hydrogels. The combination of radius ladders and CE produces a large amount of
      internally consistent data on hydrodynamic size. This technique will have
      applicability to the study of the role of hydrodynamic size on transport.

PMID- 15861470
TI  - Self-supported heterogeneous titanium catalysts for enantioselective carbonyl-ene
      and sulfoxidation reactions.
AB  - A new strategy for the heterogenization of chiral titanium complexes was
      developed by the in situ assembly of bridged multitopic BINOL ligands with
      [Ti(OiPr)4] without using a support. The assembled heterogeneous catalysts (self
      supported) showed excellent enantioselectivity in both the carbonyl-ene reaction
      of alpha-methylstyrene with ethyl glyoxylate (up to 98 % ee) and the oxidation of
      sulfides (up to >99 % ee). The catalytic performance of these heterogeneous
      catalytic systems was comparable or even superior to that attained with their
      homogeneous counterparts. The spacers between the two BINOL units of the ligands
      in the assembled catalysts had significant impact on the enantioselectivity of
      the carbonyl-ene reaction. This demonstrates the importance of the supramolecular
      structures of the assemblies on their catalytic behavior. In the catalysis of
      sulfoxidation, the self-supported heterogeneous titanium catalysts were highly
      stable and could be readily recycled and reused for over one month (at least
      eight cycles) without significant loss of activity and enantioselectivity (up to
      >99.9 % ee). The features of these self-supported catalysts, such as facile
      preparation, robust chiral structure of solid-state catalysts, high density of
      the catalytically active units in the solids, as well as easy recovery and simple
      recycling, are particularly important in developing methods for the synthesis of
      optically active compounds in industrial processes.

PMID- 15861471
TI  - Accurate and sensitive analysis of triplet repeat expansions by capillary
      electrophoresis.
AB  - The reliable genetic diagnostics of triplet repeat expansions by capillary
      electrophoresis (CE) remains technically challenging due to the properties of the
      repeated GC-rich sequences. The biased base composition of the analyzed sample as
      compared to the commonly used DNA size standards makes the precise repeat length
      determination questionable. The homologous allelic ladders improve the accuracy
      of the repeat length analysis significantly. Their use, however, is not devoid of
      other complications. In the approach we propose, the allelic ladders are used
      only to properly calibrate the commercially available standards which serve then
      as internal standards in reliable and economical repeat length determination. In
      this study, we have also analyzed factors that could possibly increase the
      sensitivity of mutant allele detection by increasing the overall amplification
      efficiency and long-to-short product ratio.

PMID- 15861472
TI  - Metal-directed synthesis and photophysical studies of trinuclear v-shaped and
      pentanuclear x-shaped ruthenium and osmium metallorods and metallostars based
      upon 4'-(3,5-dihydroxyphenyl)-2,2':6',2''-terpyridine divergent units.
AB  - A new series of V-shaped trinuclear metallorods and X-shaped pentanuclear
      metallostars has been prepared by the reaction of metal complexes bearing pendant
      phenolic functionalities with complexes containing electrophilic ligands.
      Specifically, {M(tpy)2} motifs (M=Ru or Os; tpy=2,2':6',2''-terpyridine) bearing
      one or two pendant 3,5-dihydroxyphenyl substituents at the 4-position of the
      central ring of the tpy have been reacted with the complexes [Ru(tpy)(Xtpy)]2+
      (X=Cl or Br) to form new ether-linked species. The energy transfer from ruthenium
      to osmium in these complexes has been investigated in detail and the efficiency
      of transfer shown to be highly temperature dependent; the energy transfer is
      highly efficient at low temperature, whereas at room temperature nonradiative and
      nontransfer deactivation of the excited {Ru(tpy)2}* domains is most significant.

PMID- 15861473
TI  - A dispensable methoxy group? Phenyl fencholate as a chiral modifier of n
      butyllithium.
AB  - Phenyl fenchol forms a 3:1 aggregate with n-butyllithium (3-BuLi), showing unique
      lithium-HC agostic interactions both in toluene solution (1H,7Li-HOESY) and in
      the solid state (X-ray analysis). Although methoxy-lithium coordination is
      characteristic for many mixed aggregates of anisyl fencholates with n
      butyllithium, endo-methyl coordination to lithium ions compensates for the
      missing methoxy groups in 3-BuLi. This gives rise to a different orientation of
      the fenchane moiety, encapsulating and chirally modifying the butylide unit.

PMID- 15861474
TI  - Efficient solid-phase synthesis of peptide-based phosphine ligands: towards
      combinatorial libraries of selective transition metal catalysts.
AB  - A new methodology for the solid-phase synthesis of peptide-based phosphine
      ligands has been developed. Solid supported peptide scaffolds possessing either
      primary or secondary amines were synthesised using commercially available Fmoc
      protected amino acids and readily available Fmoc-protected amino aldehydes for
      reductive alkylation, in standard solid-phase peptide synthesis (SPPS). Phosphine
      moieties were introduced by phosphinomethylation of the free amines as the final
      solid-phase synthetic step, immediately prior to complexation with palladium(II),
      thus avoiding tedious protection/deprotection of the phosphine moieties during
      the synthesis of the ligands. The extensive use of commercial building blocks and
      standard SPPS makes this methodology well suited for the generation of solid
      phase combinatorial libraries of novel ligands. Furthermore, it is possible to
      generate several different phosphine ligand libraries for every peptide scaffold
      library synthesised, by functionalising the scaffold libraries with different
      phosphine moieties. The synthesised ligands were characterised on solid support
      by conventional (31)P NMR spectroscopy and, cleaved from the support, as their
      phosphine oxides by HPLC, (1)H NMR, (31)P NMR and high resolution ESMS.
      Palladium(II) allyl complexes were generated from the resin bound ligands and to
      demonstrate their catalytic properties, palladium catalysed asymmetric allylic
      substitution reactions were performed. Good yields and moderate
      enantioselectivity was obtained for the selected combination of catalysts and
      substrate, but most importantly the concept of this new methodology was proven.
      Screening of ligand libraries should afford more selective catalysts.

PMID- 15861475
TI  - Cyanide-bridged vitamin B12-cisplatin conjugates.
AB  - cis-[PtCl(OH2)(NH3)2]+, the monoactivated form of cisplatin, reacts with the
      cyano ligand of cobalt in vitamin B12 (cyanocobalamin) to form a Co-C[triple
      chemical bond]N-Pt conjugate (1). Compound 1 is prepared in good yield directly
      in aqueous solution. The remaining chloride ligand of Pt(II) is labile. It
      hydrolyzes slowly in aqueous solution and can be exchanged by stronger
      coordinating ligands, such as 9-methylguanine or 2'-deoxyguanosine, to yield
      vitamin B12-nucleobase conjugates. X-ray structures of the vitamin B12-cisplatin
      conjugate 1 as well as of the product with coordinated 9-methylguanine (2) are
      presented. The coordination geometry at Pt(II) is almost perfectly square-planar.
      The structure of the cobalamin compound remains essentially unchanged when
      compared with the original B(12) structure. The guanine moiety of compound 2
      binds in a 45 degrees angle to the cisplatin molecule and interacts with
      neighboring molecules by means of pi stacking and hydrogen bonds.

PMID- 15861476
TI  - Acid-base and metal-ion binding properties of the RNA dinucleotide uridylyl-(5'-
      >3')-[5']uridylate (pUpU3-).
AB  - It is well known that Mg2+ and other divalent metal ions bind to the phosphate
      groups of nucleic acids. Subtle differences in the coordination properties of
      these metal ions to RNA, especially to ribozymes, determine whether they either
      promote or inhibit catalytic activity. The ability of metal ions to coordinate
      simultaneously with two neighboring phosphate groups is important for ribozyme
      structure and activity. However, such an interaction has not yet been quantified.
      Here, we have performed potentiometric pH titrations to determine the acidity
      constants of the protonated dinucleotide H2(pUpU)-, as well as the binding
      properties of pUpU3- towards Mg2+, Mn2+, Cd2+, Zn2+, and Pb2+. Whereas Mg2+,
      Mn2+, and Cd2+ only bind to the more basic 5'-terminal phosphate group, Pb2+, and
      to a certain extent also Zn2+, show a remarkably enhanced stability of the
      [M(pUpU)]- complex. This can be attributed to the formation of a macrochelate by
      bridging the two phosphate groups within this dinucleotide by these metal ions.
      Such a macrochelate is also possible in an oligonucleotide, because the basic
      structural units are the same, despite the difference in charge. The formation
      degrees of the macrochelated species of [Zn(pUpU)]- and [Pb(pUpU)]- amount to
      around 25 and 90 %, respectively. These findings are important in the context of
      ribozyme and DNAzyme catalysis, and explain, for example, why the leadzyme could
      be selected in the first place, and why this artificial ribozyme is inhibited by
      other divalent metal ions, such as Mg2+.

PMID- 15861477
TI  - An efficient three-step synthesis of cyclopenta[b]pyrans via 2-donor-substituted
      fischer ethenylcarbenechromium complexes.
AB  - A wide range of cyclopenta[b]pyrans 4 has been synthesized in a one-pot reaction
      by treatment of different 2-donorsubstituted ethenylcarbenechromium complexes 2
      with alkynes in THF in moderate to excellent yields (41-90 % for 14 out of 25
      examples). The starting materials 2 are readily available in good to excellent
      yields (76-99 % for 25 out of 36 examples) by Michael addition of amines,
      alcohols and thiols, respectively, to the corresponding alkynylcarbenechromium
      complexes 1. Due to their 10 pi-electrons in a cross-conjugated bicyclic system,
      cyclopenta[b]pyrans have been termed pseudoazulenes, as they indeed have similar
      UV/Vis-spectroscopic properties.

PMID- 15861478
TI  - Electronic structure, spectra, and magnetic circular dichroism of cyclohexa-,
      cyclohepta-, and cyclooctapyrrole.
AB  - Three recently obtained expanded porphyrins represent nice examples of compounds
      for which the electronic and spectral properties can be predicted from symmetry
      considerations alone. Perimeter-model-based theoretical analysis of the
      electronic structure of doubly protonated cyclo[6], cyclo[7], and cyclo[8]pyrrole
      leads to the anticipation of qualitatively the same electronic absorption and
      magnetic circular dichroism patterns for all three compounds. These predictions
      are fully confirmed by experiments, as well as DFT and INDO/S calculations. Due
      to a characteristic pattern of frontier molecular orbitals, a degenerate HOMO and
      a strongly split LUMO pair, the three cyclopyrroles show comparable absorption
      intensity in the Q and Soret regions. Magnetic circular dichroism spectra reveal
      both A and B Faraday terms, of which the signs and magnitudes are in remarkably
      good agreement with theoretical expectations. The values of the magnetic moments
      of the two lowest degenerate excited states have also been obtained.

PMID- 15861479
TI  - High affinity, sequence specific DNA binding by synthetic tripyrrole-peptide
      conjugates.
AB  - Linking the basic region of a bZIP transcription factor to a distamycin-like
      tripyrrole peptide by means of a nitrogen-containing tether produces a hybrid
      capable of high-affinity recognition of specific, designated DNA sequences. The
      importance of the nitrogen in the tether is shown by the considerable reduction
      in affinity (more than 10-fold) caused by its replacement with an ether linkage.
      Attachment of an aminopropyl chain on the pyrrole adjacent to the pyrrole bearing
      the nitrogen-containing tether increases affinity approximately one order of
      magnitude. These results confirm that a suitable location of protonated amine
      groups on designed DNA-binding peptides provides for higher affinities, most
      probably because of the generation of salt bridged contacts with the
      phosphodiester backbone.

PMID- 15861480
TI  - Supramolecular assemblies of a series of 2-arylbenzimidazoles at the air/water
      interface: in situ coordination, surface architecture and supramolecular
      chirality.
AB  - The spreading behavior and supramolecular assemblies of some arylbenzimidazoles
      with 2-substituted aromatic groups such as phenyl, naphthyl, anthryl and pyrenyl
      on water surface and the subphase containing AgNO3 were investigated. It was
      observed that although these compounds lack long alkyl chains, they showed
      surface activity when spread from chloroform solution on water surface and formed
      the supramolecular assemblies. When AgNO3 was present in the subphase, a
      coordination between the imidazole group of the compounds and Ag(I) occurred in
      situ in the spreading film, which was verified by the surface pressure/area (pi
      A) isotherms and UV/Vis absorption spectra. Both the spreading films from water
      and the aqueous AgNO3 subphase were transferred onto solid substrates and their
      surface morphologies as well as properties were characterized by AFM, UV/Vis
      absorption and CD spectra. Various surface morphologies such as nanoparticles,
      block domains and nanoutensils were observed depending on the substituted
      aromatic groups. Interestingly, although all of these compounds were achiral,
      supramolecular chirality was obtained for some of the arylbenzimidazole films
      assembled from either the water surface or the subphase containing AgNO3. It was
      revealed that chiral assemblies could be obtained from water surface for the
      benzimidazoles which have pyrenyl or alpha-naphthyl groups. For benzimidazole
      derivative with anthryl group, chiral assemblies could be obtained when spreading
      on the aqueous AgNO3 subphase. For the benzimidazoles with phenyl or beta
      naphthyl groups, no chirality was obtained. It was suggested that both the
      overcrowded stacking of the aromatic groups and the cooperative arrangement of
      the molecules on water surface or aqueous AgNO3 subphase play a crucial role in
      forming the chiral supramolecular assemblies.

PMID- 15861481
TI  - Spectroscopic evidence for a dinitrogen complex of gallium and estimation of the
      Ga-N2 bond strength.
AB  - Matrix-isolation experiments were performed to study the interaction between Ga
      atoms and N2 by using Raman and UV/Vis spectroscopies for detection and analysis.
      It was revealed that a weak complex is formed, for which resonance Raman spectra
      were obtained. Several overtones were sighted, allowing a rough estimate of the
      Ga-N2 fragmentation energy to be made (approximately 19 kJ mol(-1)). The
      excitation profile obtained from the spectra at different laser wavelengths
      agrees with the UV/Vis spectrum and shows that the complex exhibits an electronic
      transition at around 410 nm. At the Ga atom, this transition can be described as
      a 2S<--2P or 2D<--2P excitation, which is red-shifted from its position for free
      Ga atoms (approximately 340 nm and 270 nm for 2S<--2P and 2D<--2P, respectively)
      as a result of N2 complexation. The effect of complexation involves, therefore,
      only slight stabilization of the 2P ground state but relatively strong
      stabilization of the excited (2)S state. Accordingly, for the Ga atom in its
      excited 2S state, the Ga-N2 bond energy can be estimated to be around 79 kJ mol(
      1).

PMID- 15861482
TI  - Use of specific functionalised tips with STM: a new identification method of
      ester groups and their molecular structure in self-assembled overlayers.
AB  - The influence of chemical modification of scanning tunnelling microscopy tips on
      image contrast is studied. This technique is applied to the identification of an
      ester functional group, hardly visible otherwise. Self-assembled overlayers of
      wax esters [CH3-(CH2)14-CO-O-(CH2)15-CH3], adsorbed at the interface between
      highly oriented pyrolitic graphite and a solution of phenyloctane, are imaged.
      The gold tips used are chemically modified by 4-mercaptobenzoic acid and 4
      mercaptotoluene. The stability of the ordered overlayers formed facilitates the
      reproducible set of images with submolecular resolution. This allows the
      identification of the layer regular structure and of other features within
      molecules, which can be unambiguously related to the fingerprints of the COO
      bond. Moreover, we are interested in finding evidence of molecular motions
      observed at domain boundaries.

PMID- 15861483
TI  - Optically active oligomer units in aggregates of a highly unsaturated, optically
      inactive carotenoid phospholipid.
AB  - Enantiomers of glycerophospholipids show low or no optical activity. Accordingly,
      optical activity was not observed with the R enantiomer of a highly unsaturated
      carotenoyl lysophospholipid in solution. In spite of this, strong Cotton effects
      are detected in water. The amphiphilic carotenoid-phospholipid monomers associate
      to form aggregates, whose optical activity is attributed to oligomeric entities.
      These small helical assemblies cannot exist independently. Yet, the calculated
      octamer represents the simplest repeating primary unit that sufficiently
      expresses the absorption properties and supramolecular optical activity.

PMID- 15861485
TI  - Homochiral conglomerates and racemic crystals in two dimensions: tartaric acid on
      Cu(110).
AB  - Two-dimensional lattice structures formed by racemic tartaric acid on a single
      crystalline Cu(110) surface have been studied and compared with the enantiopure
      lattices. At low coverage, the doubly deprotonated bitartrate species is
      separated into two-dimensional conglomerates showing opposite enantiomorphism. At
      higher coverage, however, a singly deprotonated monotartrate species forms a
      heterochiral, racemic crystal lattice. While the enantioseparated bitartrate
      system undergoes decomposition at the same temperature as the enantiopure system,
      the racemic monotartrate lattice has a lower thermal stability than the
      enantiopure lattice of identical periodicity and surface density. At monolayer
      saturation coverage, the pure enantiomers form a denser lattice than the
      racemate. This is in contrast to the three-dimensional tartaric acid crystals,
      where the racemate crystallizes in a lattice of higher density, which is also
      more thermally stable than the enantiopure tartaric acid crystals.

PMID- 15861484
TI  - Heat perturbation of bovine eye lens alpha-crystallin probed by covalently
      attached ratiometric fluorescent dye 4'-diethylamino-3-hydroxyflavone.
AB  - Bovine eye lens alpha-crystallin was covalently labeled with 6-bromomethyl-4'
      diethylamino-3-hydroxyflavone and studied under native-like conditions and at the
      elevated temperature (60 degrees C) that is known to facilitate alpha-crystallin
      chaperone-like activity. This novel SH-reactive two-band ratiometric fluorescent
      probe is characterized by two highly emissive N*- and T*-bands; the latter
      appears due to excited state intramolecular proton transfer reaction. The
      positions of these bands and the ratio of their intensities for the alpha
      crystallin-dye conjugate are the sensitive indicators of polarity of the dye
      environment and its participation in intermolecular hydrogen bonding. Although we
      found that the dye labels both the SH and the NH2 groups in alpha-crystallin, a
      recently developed procedure allowed us to distinguish between the heat-induced
      spectral changes of the dye molecules attached to SH and NH2 groups. We observed
      that at elevated temperature the environment of the SH-attached dye becomes more
      polar and flexible. The number of H-bond acceptor groups in the vicinity of the
      dye decreases. Since alpha-crystallin contains a single Cys residue within the C
      terminal domain of its (alpha)A subunit (the (alpha)B subunit contains none), we
      can attribute the observed effects to temperature-induced changes in the C
      terminal domain of this protein.

PMID- 15861486
TI  - Solid-state NMR study of Schiff base derivatives of 2-hydroxynaphthaldehyde.
      Deuterium isotope effects on 15N chemical shifts in the solid state.
AB  - Schiff base derivatives of 2-hydroxynaphthylaldehyde were studied by means of 13C
      and 15N cross-polarization magic angle spinning NMR spectroscopy and deuterium
      isotope effects on 15N chemical shifts, deltaN(D), in the solid state. DeltaN(D)
      in the solid state provided evidenced for the presence of a dynamic proton
      transfer equilibrium in the solid state at the room temperature.

PMID- 15861487
TI  - US28 actions in HCMV infection: lessons from a versatile hijacker.
AB  - Mimicking host proteins is a strategy adopted by several herpesviruses to exploit
      the host cell for their own benefit. In this respect the human cytomegalovirus
      (HCMV) chemokine receptor homologue US28, has been extensively studied. Molecular
      pirates such as US28 can teach us about crucial events in HCMV infection and may
      either offer a potential target for antiviral therapy or provide an alternative
      strategy to immune suppression. Despite elaborate research into the chemokine
      binding affinity, signalling properties, intracellular trafficking and expression
      kinetics of US28, a solid hypothesis about the role of US28 in HCMV infection has
      not yet been proposed. It appears that US28 may behave as a molecular pirate that
      employs smart strategies for cell entry, host gene regulation and immune evasion.
      This review will elaborate on these aspects of US28 biology and discuss possible
      implications for HCMV infection.

PMID- 15861488
TI  - NMR investigation of hydrogen bonding and 1,3-tautomerism in 2-(2-hydroxy-5
      substituted-aryl) benzimidazoles.
AB  - The 1,3-tautomerism associated with 2-(2-hydroxy-5-substituted
      aryl)benzimidazoles was studied in different solvents. The effect of hydrogen
      bonding involving the hydroxyl group of the 2-aryl ring on the tautomerism was
      investigated using NMR spectroscopy. The influence of the solvent concentration
      on 2-(2-hydroxy-5-chloroaryl)benzimidazole was studied in acetone-d6 and DMSO-d6.

PMID- 15861489
TI  - 1H and 13C NMR identification of unexpected 3,4-dihydroquinoxalines in the
      syntheses of 1,5-benzodiazepine derivatives.
AB  - The reaction between o-phenylenediamines, dehydroacetic acid and aromatic
      aldehydes is shown to give not only the expected 1,5-benzodiazepine derivative
      but also a 3,4-dihydroquinoxaline, the structure of which was determined by its
      1H and 13C 1D and 2D NMR spectra.

PMID- 15861490
TI  - Rapid prenatal diagnosis of trisomy 21 by real-time quantitative polymerase chain
      reaction with amplification of small tandem repeats and S100B in chromosome 21.
AB  - Trisomy 21 (Down syndrome) is the most common congenital anomaly, and it occurs
      in one out of 700-1000 births. Current techniques such as amniocentesis and
      chorionic villi sampling (CVS) require lengthy laboratory culture procedures and
      high costs. This study was undertaken to establish a rapid prenatal diagnosis of
      trisomy 21 using real-time quantitative polymerase chain reaction (PCR) of fetal
      DNA from amniotic fluid. Real-time quantitative PCR was performed with DNA
      templates obtained from 14 normal blood samples, 10 normal amniotic fluid
      samples, 14 Down syndrome blood samples, and 7 Down syndrome amniotic fluid
      samples. Primers for D21S167 and S100B of chromosome 21 were used. Primers that
      direct the amplification of the 165-bp fragment of the insulin-like growth factor
      (IGF)-1 gene on chromosome 12 using a PCR primer were included to generate an
      internal standard for quantitation. The relative levels of D21S167 and S100B were
      2.6 and 2.4 times higher in the blood of Down syndrome patients than those in the
      control group. The differences between these two groups were statistically
      significant (p-values were 0.0012 and 0.0016, respectively). The relative levels
      of D21S167 and S100B were 2.1 and 2.7 times higher in the amniotic fluid of Down
      syndrome fetuses than those in the control group. The difference between these
      two groups was statistically significant (p-values were 0.0379 and 0.0379,
      respectively). Prenatal diagnosis of trisomy 21 by real-time quantitative PCR
      using STR (small tandem repeats) amplification of D21S167 and S100B is a useful,
      accurate and rapid diagnostic method. Furthermore, it may also be useful for
      prenatal diagnosis with fetal DNA from maternal blood, and for preimplantation
      genetic diagnosis and prenatal counseling.

PMID- 15861491
TI  - The prevalence of the metabolic syndrome in Korean adults: comparison of WHO and
      NCEP criteria.
AB  - The aims of this study were to compare the prevalence of the metabolic syndrome
      according to the WHO and NCEP ATP III criteria in Korean adults, and to compare
      the prevalence of the metabolic syndrome with the results in previous Korean
      studies. The study comprised 1,230 subjects (627 men, 603 women) aged 30-79 years
      (mean 52.4 +/- 10.3 years) who underwent medical check-up from April to June,
      2001 in the Korea Association of Health (KAH). The prevalence of the metabolic
      syndrome according to the modified WHO criteria was 21.8 % of men and 19.4 % of
      women. However, the prevalence was increased 1.6 times (34.2 % ) in men and 2.0
      times (38.7 % ) in women using the modified NCEP criteria. The prevalence of the
      metabolic syndrome has varied widely according to differences in the criteria.
      Thus, further studies are necessary to define the appropriate criteria of the
      metabolic syndrome for Korean adults.

PMID- 15861492
TI  - The effects of the acupuncture treatment for smoking cessation in high school
      student smokers.
AB  - The use of alternative medicine for smoking cessation have been increasing
      steadily in recent years. A series of clinical group studies was performed to
      clarify the effect, outcome and success rate of an acupuncture treatment for
      smoking cessation. This study was conducted for four weeks using 238 smoking
      students at 2 high schools. The subjects were separated into two groups: 159
      students were treated with acupuncture on the anti-smoking acupoints of the ear,
      which is known to be effective for cessation of smoking (case group), and 79
      students were treated at other sites of the ear (control group). The acupuncture
      treatment was alternately administered at each side of the ears on a weekly basis
      for 4 weeks. The smoking cessation success was only 1 case (0.6%) in the case
      group and none in the control group after 4 weeks. The change in the taste of
      tobacco and the intensity of the desire to smoke were not significantly different
      between the case and control groups, but the case group showed a tendency of
      reduction in the taste of tobacco and the intensity of the desire to smoke. In
      addition, the reduction in cigarette consumption was not significant, but the
      tendency of reduction in the study group was significant. It is believed that the
      site of auricular acupuncture for smoking cessation is not important. However,
      there was a significant tendency in terms of the reduction in cigarette
      consumption, the taste of tobacco and the intensity of the desire to smoke in the
      case group, indicating that auricular acupuncture in smoking cessation has some
      effect.

PMID- 15861493
TI  - Clinical usefulness of cervicogram as a primary screening test for cervical
      neoplasia.
AB  - The purpose of this study is to evaluate the clinical usefulness of the
      cervicogram as a primary screening test for cervical neoplasia. A total of 294
      women who had undergone a cervicogram and a Pap test between January and July
      2003, were selected. The diagnostic accuracy of the Pap test, cervicogram, and
      the Pap test combined with a cervicogram were compared with the histopathologic
      diagnosis. Among 294 women, the Pap test was negative in 130 cases and positive
      in 164 cases. Among patients with positive Pap test, cervicogram were negative in
      101 cases (61.6%) and positive in 63 cases (38.4%). The diagnostic accuracy
      between cervicogram with positive Pap test and histology was as follows;
      sensitivity 44.9%, specificity 78.3%, positive predictive value 84.1%, negative
      predictive value 32.7%, false positive rate 15.9%, and false negative rate 67.3%.
      Although the adjunctive use of cervicogram with the Pap test in the initial
      screening of cervical neoplasia showed a higher specificity and higher positive
      predictive value compared to the Pap test alone, consideration in terms of lower
      sensitivity, lower positive predictive value, higher false positive rate and cost
      effectiveness should be given in lieu of clinically applying cervicogram with the
      pap test as an initial screening test.

PMID- 15861494
TI  - Prognostic value of tumor volume in nasopharyngeal carcinoma.
AB  - Tumor bulk has been recognized as an important prognostic factor in the treatment
      of malignancy. The purpose of the present study is to investigate the prognostic
      value of tumor volume in nasopharyngeal carcinoma. Sixty patients with
      nasopharyngeal carcinoma were included in this study. Tumor contour was outlined
      on each of the computed tomography (CT) images using an image analyzer. The
      primary tumor volume (PTV) and nodal tumor volume (NTV) were calculated by a
      summation-of-areas technique, and the maximal perimeter of primary tumor (MPP)
      was measured. The loco-regional control rates and disease-specific survival rates
      were analyzed according to several variables. The patients had a 5-year local
      control rate of 75.5%, 5-year nodal control rate of 74.6%, and 5-year disease
      specific survival rate of 60.2%. Large PTV ( > 30 cm3) was associated with a
      significantly lower local control (p=0.005). Large NTV ( > 5 cm3) was associated
      with a significantly lower nodal control (p=0.019) and lower disease-specific
      survival (p=0.046). Large MPP ( > 18 cm) was associated with a significantly
      lower local control (p=0.017). In multivariate analysis, the PTV and NTV were
      found to be independent factors in predicting the local (p=0.015) and nodal
      (p=0.039) control, respectively. The NTV (p=0.012) and cranial nerve involvement
      (p=0.009) were factors that predicted disease-specific survival. Our results
      suggest that the estimation of tumor volume may identify a subgroup of patients
      with a greater risk of loco-regional failure and can be used to refine the
      current staging system.

PMID- 15861495
TI  - Chondrosarcoma of the head and neck.
AB  - Chondrosarcoma of the head and neck region is a rare disease, representing
      approximately 0.1% of all head and neck neoplasms. The 5-year survival rate of
      chondrosarcoma is 70-80%, showing relatively good prognosis; however, it is known
      to progress slowly and eventually cause multiple metastases. In this study, we
      reviewed chondrosarcoma cases experienced at Yonsei University Medical College
      during the last 15 years to investigate its clinical characteristics and
      treatment outcome. The medical records of 8 patients who were diagnosed with
      chondrosarcoma of the head and neck region and underwent surgical treatment
      between December 1990 and December 2002 were retrospectively reviewed. The
      primary sites were sinus, mastoid, jugular foramen and thyroid cartilage. In all
      patients, the initial treatment modality was surgery, and postoperative radiation
      therapy was performed in 4 cases. The pathological findings showed chondrosarcoma
      in 7 cases and mesenchymal chondrosarcoma in 1 case. The treatment outcome
      resulted in 3 cases of recurrence, of which 2 cases were treated successfully and
      the other case expired of disease, indicating a survival rate of 87.5%. In the
      case that resulted in death, complete excision could not be achieved. Therefore,
      we concluded that wide excision is a beneficial initial treatment of this rare
      disease.

PMID- 15861496
TI  - Assisted cough and pulmonary compliance in patients with Duchenne muscular
      dystrophy.
AB  - The aim of this study was to investigate the factors affecting cough ability, and
      to compare the assisted cough methods in patients with Duchenne muscular
      dystrophy (DMD). A total seventy-one male patients with DMD were included in the
      study. The vital capacity (VC) and maximum insufflation capacity (MIC) were
      measured. The unassisted peak cough flow (UPCF) and three different techniques of
      assisted peak cough flow were evaluated. UPCF measurements were possible for all
      71 subjects. But when performing the three different assisted cough techniques,
      peak cough flows (PCFs) could be obtained from only 51 subjects. The mean value
      of MICs (1801 +/- 780 cc) was higher than that of VCs (1502 +/- 765 cc) (p<
      0.01). All three assisted cough methods showed a significantly higher value than
      the unassisted method (F=80.92, p< 0.01). The manual assisted PCF under MIC
      (MPCFmic) significantly exceeded those produced by manual assisted PCF (MPCF) or
      PCF under MIC (PCFmic). The positive correlation between the MIC, VC difference
      (MIC-VC), and the difference between PCFmic and UPCF (PCFmic-UPCF) was seen
      (r=0.572, p< 0.01). The preservation of pulmonary compliance is important for the
      development of an effective cough as well as assisting the compression and
      expulsive phases. Thus, the clinical importance of the inspiratory phase and
      pulmonary compliance in assisting a cough should be emphasized.

PMID- 15861497
TI  - Effects of air pollutants on childhood asthma.
AB  - Epidemiologic studies have suggested the association between environmental
      exposure to volatile organic compounds (VOCs) and polycyclic aromatic
      hydrocarbons (PAHs) and the increased risk of incurring asthma. Yet there is
      little data regarding the relationship between personal exposure to air pollution
      and the incidence of asthma in children. This study was designed to evaluate the
      effect of exposure to air pollution on children with asthma by using exposure
      biomarkers. We assessed the exposure level to VOCs by measuring urinary
      concentrations of hippuric acid and muconic acid, and PAHs by 1-OH pyrene and 2
      naphthol in 30 children with asthma and 30 children without asthma (control). The
      mean level of hippuric acid was 0.158 +/- 0.169 micromol/mol creatinine in the
      asthma group and 0.148 +/- 0.249 micromol/mol creatinine in the control group,
      with no statistical significance noted (p=0.30). The mean concentration of
      muconic acid was higher in the asthma group than in the control group (7.630 +/-
      8.915 micromol/mol creatinine vs. 3.390 +/- 4.526 micromol/mol creatinine
      p=0.01). The mean level of urinary 1-OHP was higher in the asthma group (0.430 +/
      0.343 micromol/mol creatinine) than the control group (0.239 +/- 0.175
      micromol/mol creatinine), which was statistically significant (p=0.03). There was
      no difference in the mean concentration of 2-NAP between the two groups (9.864 +/
      10.037 micromol/mol in the asthma group vs. 9.157 +/- 9.640 micromol/mol in the
      control group, p=0.96). In conclusion, this study suggests that VOCs and PAHs
      have some role in asthma.

PMID- 15861498
TI  - The effects of ketorolac injected via patient controlled analgesia
      postoperatively on spinal fusion.
AB  - Lumbar spinal fusions have been performed for spinal stability, pain relief and
      improved function in spinal stenosis, scoliosis, spinal fractures, infectious
      conditions and other lumbar spinal problems. The success of lumbar spinal fusion
      depends on multifactors, such as types of bone graft materials, levels and
      numbers of fusion, spinal instrumentation, electrical stimulation, smoking and
      some drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs). From January
      2000 to December 2001, 88 consecutive patients, who were diagnosed with spinal
      stenosis or spondylolisthesis, were retrospectively enrolled in this study. One
      surgeon performed all 88 posterolateral spinal fusions with instrumentation and
      autoiliac bone graft. The patients were divided into two groups. The first group
      (n=30) was infused with ketorolac and fentanyl intravenously via patient
      controlled analgesia (PCA) postoperatively and the second group (n=58) was
      infused only with fentanyl. The spinal fusion rates and clinical outcomes of the
      two groups were compared. The incidence of incomplete union or nonunion was much
      higher in the ketorolac group, and the relative risk was approximately 6 times
      higher than control group (odds ratio: 5.64). The clinical outcomes, which were
      checked at least 1 year after surgery, showed strong correlations with the spinal
      fusion status. The control group (93.1%) showed significantly better clinical
      results than the ketorolac group (77.6%). Smoking had no effect on the spinal
      fusion outcome in this study. Even though the use of ketorolac after spinal
      fusion can reduce the need for morphine, thereby decreasing morphine related
      complications, ketorolac used via PCA at the immediate postoperative state
      inhibits spinal fusion resulting in a poorer clinical outcome. Therefore, NSAIDs
      such as ketorolac, should be avoided after posterolateral spinal fusion.

PMID- 15861499
TI  - Behavioral characteristics of a mouse model of cancer pain.
AB  - Pain is a major symptom in cancer patients, and most cancer patients with
      advanced or terminal cancers suffer from chronic pain related to treatment
      failure and/or tumor progression. In the present study, we examined the
      development of cancer pain in mice. Murine hepatocarcinoma cells, HCa-1, were
      inoculated unilaterally into the thigh or the dorsum of the foot of male C3H/HeJ
      mice. Four weeks after inoculation, behavioral signs were observed for mechanical
      allodynia, cold allodynia, and hyperalgesia using a von Frey filament, acetone,
      and radiant heat, respectively. Bone invasion by the tumor commenced from 7 days
      after inoculation of tumor cells and was evident from 14 days after inoculation.
      Cold allodynia but neither mechanical allodynia nor hyperalgesia was observed in
      mice that received an inoculation into the thigh. On the contrary, mechanical
      allodynia and cold allodynia, but not hyperalgesia, were developed in mice with
      an inoculation into the foot. Sometimes, mirror-image pain was developed in these
      animals. These results suggest that carcinoma cells injected into the foot of
      mice may develop severe chronic pain related to cancer. This animal model of pain
      would be useful to elucidate the mechanisms of cancer pain in humans.

PMID- 15861500
TI  - Isolation of endothelial progenitor cells from cord blood and induction of
      differentiation by ex vivo expansion.
AB  - Endothelial progenitor cells (EPCs) have been reported to possess the capacity to
      colonize vascular grafts and hold promise for therapeutic neovascularization.
      However, limited quantities of EPCs have been the major factor impeding effective
      research on vasculoangiogenesis. In this study, cytokine and culture conditions
      necessary for the provision of large quantities of endothelial cells (ECs) were
      investigated. Cord blood was collected from 18 normal full-term deliveries and
      CD34+ cells were isolated by MACS system (Miltenyi Biotech, Bergish-Gladbach,
      Germany). To evaluate the effect of cytokines, CD34+ cells were cultured with
      various cytokine combinations, such as stem cell factor (SCF), flt3-ligand (FL),
      and thrombopoietin (TPO) with vascular endothelial growth factor (VEGF),
      interleukin-1 beta , fibroblast growth factor-basic (FGF-b) as basic cytokines.
      The quantities of non-adherent and adherent cells were the greatest with SCF, FL
      and TPO. The addition of TPO to all other cytokines significantly increased the
      number of non-adherent and adherent cells (p< 0.05, Wilcoxon rank sum test).
      After four weeks of culture, adherent cells expressed endothelial specific
      markers such as KDR, CD31 and CD62E. Typical morphology of ECs was observed
      during culture, such as cord-like structure and cobblestone appearance,
      suggesting that the adherent cells were consistent with ECs. In this study, the
      experimental conditions that optimize the production of ECs for therapeutic
      neovascularization were described. And it was possibly suggested that TPO plays a
      major role in differentiation from EPCs to ECs.

PMID- 15861502
TI  - Computational analysis of tumor angiogenesis patterns using a two-dimensional
      model.
AB  - Tumor angiogenesis was simulated using a two-dimensional computational model. The
      equation that governed angiogenesis comprised a tumor angiogenesis factor (TAF)
      conservation equation in time and space, which was solved numerically using the
      Galerkin finite element method. The time derivative in the equation was
      approximated by a forward Euler scheme. A stochastic process model was used to
      simulate vessel formation and vessel elongation towards a paracrine site, i.e.,
      tumor-secreted basic fibroblast growth factor (bFGF). In this study, we assumed a
      two-dimensional model that represented a thin (1.0 mm) slice of the tumor. The
      growth of the tumor over time was modeled according to the dynamic value of bFGF
      secreted within the tumor. The data used for the model were based on a previously
      reported model of a brain tumor in which four distinct stages (multicellular
      spherical, first detectable lesion, diagnosis, and death of the virtual patient)
      were modeled. In our study, computation was not continued beyond the 'diagnosis'
      time point to avoid the computational complexity of analyzing numerous vascular
      branches. The numerical solutions revealed that no bFGF remained within the
      region in which vessels developed, owing to the uptake of bFGF by endothelial
      cells. Consequently, a sharp declining gradient of bFGF existed near the surface
      of the tumor. The vascular architecture developed numerous branches close to the
      tumor surface (the brush-border effect). Asymmetrical tumor growth was associated
      with a greater degree of branching at the tumor surface.

PMID- 15861501
TI  - In vitro bioassay of endotoxin using fluorescein as a pH indicator in a
      macrophage cell culture system.
AB  - Based on the biological activity of endotoxin, we propose a possible new method
      for detecting endotoxin using a pH-indication system of macrophage culture media.
      After RAW 264.7 macrophage cells were treated with lipopolysaccharide (LPS), the
      addition of fluorescein to the LPS-treated media reproductively reduced its
      absorption and emission spectra (it was a dose-dependent reduction). The
      advantages of this LPS-detection method were compared with the Limulus Amebocyte
      Lysate (LAL) test by using purified bacterial LPS (Salmonella minnessota,
      Escherichia coli, and Pseudomonas aeruginosa). Additionally, the absorption and
      fluorescence intensity of fluorescein, following treatment of RAW 264.7 cells
      with a high concentration of Staphylococcus aureus (Gram-positive, lysed
      bacteria), could not generally be detected by the LAL test, but they were found
      to be reduced, in a dose-response relationship, with this new system. The
      macrophage culture system-method might be a good supplement to the LAL assay for
      detection of LPS, Gram-negative and Gram-positive bacteria.

PMID- 15861503
TI  - Concurrence of ring 21 and trisomy 21 in children of normal parents.
AB  - We present a case of two siblings with different chromosome 21 abnormalities that
      are both de novo [r(21)/i(21p13) mosaicism and rob(14;21)]. Molecular studies
      using polymorphic markers have shown that these two aberrations had a common
      maternal origin. However, the parents were cytogenetically and phenotypically
      normal. This unusual association has not been reported and is considered to be a
      unique case that should be addressed.

PMID- 15861504
TI  - Mesenteric Castleman's disease.
AB  - We report here a rare case of mesenteric Castleman's disease presenting as a
      mesenteric mass. A 13-year-old female child was admitted to our hospital
      complaining of intermittent vague abdominal pain. She had hypochromic anemia,
      thrombocytosis and an elevated erythrocyte sedimentation rate (ESR).
      Ultrasonography and computed tomography indicated an intra- abdominal mass might
      represent a lymphoma or gastrointestinal stromal tumor or leiomyoma, but the
      definitive preoperative diagnosis couldn't be confirmed. The surgical resection
      of the mass revealed the mesenteric hyaline vascular-type Castleman's disease.

PMID- 15861505
TI  - Pneumomediastinum due to intractable hiccup as the presenting symptom of multiple
      sclerosis.
AB  - Pneumomediastinum and subcutaneous emphysema generally occurs following trauma to
      the esophagus or lung. It also occurs spontaneously in such situations of
      elevating intra-thoracic pressure as asthma, excessive coughing or forceful
      straining. We report here on the rare case of a man who experienced the signs of
      pneumomediastinum and subcutaneous emphysema after a prolonged bout of
      intractable hiccup as the initial presenting symptoms of multiple sclerosis.

PMID- 15861506
TI  - Bilateral congenital anophthalmos and agenesis of the optic pathways.
AB  - This report presents a rare example of a bilateral congenital anophthalmos and an
      agenesis of the optic pathways. The MR imaging studies revealed that the
      eyeballs, optic nerves, optic chiasm, optic tracts and optic radiation were
      absent. The chromosomal examination was normal. Mild mental retardation was also
      observed. Apart from the rarity of the anophthalmos and the total absence of the
      optic pathways, no etiologic reason for this pathology could be detected, which
      makes this case more significant.

PMID- 15861507
TI  - Optic nerve injury secondary to endoscopic sinus surgery: an analysis of three
      cases.
AB  - Major orbital complications after the endoscopic sinus surgeries are rare and of
      these, optic nerve injury is one of the most serious. This study was to
      undertaken to analyze 3 cases of optic nerve injury after endoscopic sinus
      surgery. The three cases included one patient with a loss of visual acuity and
      visual field defect, and two patients with total blindness. In all cases, no
      improvement of visual acuity was observed despite treatment. It is important to
      frequently check the location and direction of the endoscope during surgery to
      avoid optic nerve injury. In addition, surgeons must have a precise knowledge of
      the detailed anatomy through cadaver dissections, an ability to interpret the PNS
      CT scan and experienced procedural surgical skills.

PMID- 15861508
TI  - Pulmonary edema following phenylephrine intranasal spray administration during
      the induction of general anesthesia in a child.
AB  - Topical phenylephrine, an agent used to facilitate nasotracheal intubation and
      prevent nasal mucosal bleeding, can cause severe hypertension in some patients,
      secondary to its stimulation of alpha-adrenergic receptors. Moreover, a high
      incidence of pulmonary edema is found in patients whose phenylephrine
      administration is followed by treatment with beta-blocking agents. We report a
      case of acute pulmonary edema in a pediatric patient who developed severe
      hypertension after the inadvertent administration of a large dose of topical
      nasal phenylephrine, followed by beta-adrenergic antagonists (esmolol).

PMID- 15861509
TI  - Multidisciplinary diagnostic approach for left ventricular
      hypertrabeculation/noncompaction.

PMID- 15861510
TI  - Croatian implementation of a computer-based teaching program from the University
      of Kansas, USA.
AB  - AIM: To determine whether the students enrolled in the computer-based teaching
      program would take the final examination in pathology earlier than those who
      studied according to the previous traditional program. METHODS: The study
      included all medical students enrolled in the pathology course at the Zagreb
      University School of Medicine, Zagreb, Croatia, between 1995/96 and 2000/01
      academic years. In the fall of 1998, computer-based teaching program from the
      University of Kansas was implemented at the Zagreb University School of Medicine,
      with 48 of the class of 225 students (20%) randomly enrolled in the program. The
      remaining 80% of students of the same class were enrolled in the traditional
      teaching program used at the Zagreb University School of Medicine. We compared
      the success of these two groups of students at the final pathology examination in
      the first term. Following this initial observational period, all students in the
      next two years (1999/00 and 2000/01), were enrolled in the computer-based
      teaching program. Pass rates of these students at the final examination taken in
      the first term were compared with the pass rates of students who studied
      according to the traditional teaching program during the period from 1995 to
      1998. RESULTS: In 1998, 58.3% of students from the computer-based teaching
      program group chose to take the final examination in the first term, compared
      with only 32.2% of students from the traditional teaching program group (chi(2)
      (1)=10.97, P<0.001). Students in the computer based program had better final
      examination mean scores (-/+ standard deviation) than students in the traditional
      program (81.9-/+9.8 and 73.3-/+14.2, respectively; t=2.908, P=0.005). Upon the
      implementation of the computer-based teaching program for the entire class in
      1999 and 2000, the number of students taking the final examination in the first
      term increased more than we expected on the basis of the data from the academic
      years 1995 to 1998 (chi(2) (5)=39.60, P<0.001). CONCLUSION: The computer-based
      program introduced at the Zagreb University School of Medicine in 1998 had a
      positive effect on medical students, as evidenced by the fact that more students
      chose to take the final pathology examination in the first term and more of them
      passed the examination in the first attempt than those in the traditional
      teaching program.

PMID- 15861511
TI  - Gene expression profiling in lymphoma diagnosis and research.
AB  - Gene expression profiling in the past 5 years has generated a large amount of
      data on a variety of malignancies. Unique gene expression signatures have been
      identified for the more common types of non-Hodgkin lymphoma (NHL), including
      clinically and biologically important subsets that have not been defined before.
      In addition, molecularly defined prognosticators have also been constructed for
      the major types of NHL and these prognosticators provide added value to the
      widely used International Prognostic Index. The new information should be
      included in our evaluation of NHL patients, especially when conducting clinical
      trials. Studies are ongoing to validate and refine these diagnostic and
      prognostic signatures and to develop platforms that are suitable for routine
      clinical applications. Similar studies will be performed on the less common types
      of NHL to complete the molecular classification of NHLs. It is also anticipated
      that gene expression profiling studies will lead to the identification of novel
      targets for the development of new therapeutic agents for NHL.

PMID- 15861512
TI  - Risk-adapted multimodal laboratory cervical screening -- application of new
      technologies to cervical cancer prevention.
AB  - The objective of screening for cervical cancer is to reduce the mortality and
      incidence of the disease. To date, there is extensive and strong evidence that
      this can be achieved by cytology-based screening programs, which continue to be
      the mainstay of cervical prevention worldwide despite their inherent
      methodological limitations. This article presents a review on the utility of
      conventional, ancillary, and experimental methods for cervical screening both as
      single tests and test-combinations, and describes possible future directions for
      enhanced screening accuracy using risk-adapted protocols.

PMID- 15861513
TI  - Nordic immunohistochemical quality control.
AB  - The use of immunohistochemistry by pathologists has been steadily, almost
      logarithmically increasing during the last decade. There is no scientific
      indication that this trend will reverse or slow down. At the same time, quality
      control issues have not followed this tempo. In particular, external quality
      control has been neglected. In 1999, nine Scandinavian laboratories established
      organization, Nordic Quality Control (NordiQC), to provide external quality
      control in immunohistochemistry for Denmark, Norway, Sweden, and Finland. This
      commentary briefly describes the work of this organization.

PMID- 15861514
TI  - Syk tyrosine kinase expression during multistep mammary carcinogenesis.
AB  - AIM: To analyze the expression of Syk tyrosine kinase, recently implicated as a
      tumor suppressor in mammary carcinogenesis, during the multi step development of
      human breast carcinoma. METHODS: Syk expression was examined in invasive
      carcinomas of the breast and in corresponding premalignant epithelial lesions in
      50 women, using immunohistochemical method and semi-quantitative scoring system
      (H-score). The results were correlated with the expression of Syk in the lymph
      node metastases. RESULTS: Syk was strongly and uniformly expressed in normal
      mammary epithelium (H score=2.36-/+0.75), and no significant reduction in Syk
      expression was observed in hyperplastic lesions (H=2.31-/+0.87), carcinoma in
      situ (H=1.90-/+0.93), or invasive carcinomas (H=1.83-/+0.88). Loss of Syk
      expression (defined as H< or =1.0) was seen in approximately 1/5 of invasive
      breast carcinomas, but the majority of metastatic carcinomas (15/21) still
      strongly expressed Syk, irrespective of Syk expression in primary tumor.
      CONCLUSION: The loss of Syk characterizes a subset of breast carcinomas but does
      not apparently contribute to the development of the metastatic potential of these
      carcinomas, limiting the potential diagnostic utility of immunohistochemical test
      in the prediction of malignant behavior.

PMID- 15861515
TI  - Axillary recurrence rate in breast cancer patients with negative sentinel lymph
      node.
AB  - AIM: To assess the axillary recurrence rate in operable breast cancer patients
      with clinically negative axilla after negative sentinel lymph node in whom
      axillary lymph node dissection had not been performed. METHODS: Fifty consecutive
      female operable breast cancer patients with negative sentinel lymph node biopsy
      in whom axillary lymph node dissection had not been performed were included in
      the study and prospectively followed, with median follow-up time of 32 months
      (range 10-50 months). Sentinel lymph node biopsy was performed by the triple
      method. RESULTS: The sentinel node identification rate was 100%. In only one of
      50 patients with negative sentinel lymph node, axillary recurrence developed 26
      months after surgery. This was the sole patient with sentinel lymph node biopsy
      after previous surgical biopsy. After treatment, all patients were alive and with
      no evidence of disease. CONCLUSIONS: Omitting axillary node dissection after
      negative sentinel node biopsy in operable breast cancer patients proved to be
      safe. Patients with previous open surgical biopsy should be given special
      attention in the follow-up.

PMID- 15861516
TI  - Immunohistochemical evaluation of cyclin D1 in breast cancer.
AB  - AIM: To explore the potential prognostic value of cyclin D1 in invasive breast
      cancer and its correlation with basic histopathological parameters, hormonal
      status (estrogen [ER] and progesterone receptor [PR]), and bcl-2. METHODS:
      Medical records of 48 patients, diagnosed in 1998, from the Central Database of
      the Institute of Oncology, Clinical Center University of Sarajevo, were analyzed.
      The mean follow-up was 61 months (range: 4-103 months). Routine histopathological
      evaluation was performed for 48 formalin-fixed and paraffin-embedded tissue
      samples. For immunohistochemical staining, we used monoclonal antibodies for ER,
      PR, bcl-2, and cyclin D1. RESULTS: Cyclin D1 expression inversely correlated with
      tumor grade (P=0.010) and tumor size (P=0.023), whereas significant positive
      association was found with ER (P=0.001) and bcl-2 (P=0.001) expression. Patients
      with higher cyclin D1 expression had longer both overall survival (P=0.014) and
      relapse-free survival (P=0.037). Cox regression analysis for overall survival
      (OS) showed that lymph node status, ER expression, therapy, and cyclin D1
      expression were independent prognostic factors. (P range from 0.003 to 0.04).
      CONCLUSION: Expression of cyclin D1 is associated with better disease outcome in
      breast cancer.

PMID- 15861517
TI  - Expression of bone morphogenetic proteins in human metastatic prostate and breast
      cancer.
AB  - AIM: To analyze the expression of bone morphogenetic proteins (BMPs) in prostate
      and breast cancers with established metastasis in bone, where prostate cancer
      causes osteoblastic metastases, and breast cancer osteolytic metastases. METHODS:
      Primary tumor specimens from 20 patients with prostate cancer and 15 with breast
      cancer were studied for BMP-2/4, -3, -5, -6 and -7 immunohistochemistry. All
      patients had multiple bone metastases proven by bone scan. We also examined BMPs
      expression in normal prostate and breast tissues. BMPs expression was compared
      with clinicopathological and biochemical parameters. RESULTS: Cytoplasmic BMPs
      immunostaining was observed in both prostate cancer and normal prostate tissue.
      Expression of BMP-2/4, -5, -6, and -7 proteins was detected in all normal
      prostate samples, with the predominance of BMP-2/4 (87.8-/+11.4% positive cells)
      and BMP-7 (94.6-/+0.9% positive cells). In prostate cancer tissues, we found
      variable expression of all BMPs. BMP-2/4 (83-/+11.6% positive cells) was
      predominantly expressed in prostate carcinoma, whereas the expression of BMP-7
      (24.3-/+19.2% positive cells) was significantly lower than in the normal
      prostate. In all breast cancers tissues, we found nuclear staining only for BMP
      7. In normal breast tissue, the BMP expression was not detectable. The percent of
      BMP-7 positive cells in breast cancer (86.4-/+7.3%) was higher than in prostatic
      cancer. Comparing BMP expression levels and clinicopathological parameters, we
      did not find statistical difference, except for serum alkaline phosphatase, which
      was significantly higher in patients with prostate cancer. CONCLUSION: The
      expression of BMPs differs between prostate and breast cancer cells. Identifying
      the BMP proteins in cancers may be useful for monitoring the tumor status with
      reference to metastases.

PMID- 15861518
TI  - Adenocarcinoma of uterine cervix -- prognostic significance of clinicopathologic
      parameters.
AB  - AIM: To investigate prognostic significance of several clinicopathologic
      parameters in patients with adenocarcinoma of the uterine cervix. METHODS: We
      retrospectively studied 36 patients treated at the Department of Gynecology and
      Obstetrics, Zagreb University School of Medicine, Croatia, in the period from
      1978-1998. Cox proportional hazard analysis was performed to examine the
      prognostic significance of menstrual status, clinical stage, architectural grade,
      nuclear grade, DNA ploidy, proliferative activity, and mode of therapy. RESULTS:
      The 5-year survival for this group of patients was 75%. The following parameters
      proved to be statistically significant in a univariate analysis: clinical stage
      (P=0.042), architectural grade (P=0.009), and nuclear grade (P=0.002). In the
      multivariate analysis, the nuclear grade (P=0.007) turned out to be the only
      statistically significant parameter. According to the nuclear grade, the five
      year survival was 80% in the prognostically favorable and only 30% in the
      unfavorable group of patients. CONCLUSION: Our data showed that in patients with
      adenocarcinoma of the uterine cervix the nuclear grade, clinical stage, and
      architectural grade of the tumor represent the most important prognostic
      parameters. The analysis of DNA ploidy and proliferative activity had no
      prognostic significance.

PMID- 15861519
TI  - Pathological changes in placentas from pregnancies with preeclampsia and
      eclampsia with emphasis on persistence of endovascular trophoblastic plugs.
AB  - AIM: To assess the frequency and types of histopathological changes in placentas
      from pregnancies complicated by preeclampsia/eclampsia. METHODS: Placentas
      routinely sent for pathological examination (n=1,689) were studied
      microscopically and compared to findings of 50 placentas from uncomplicated
      pregnancies. RESULTS: Out of 1,689 placentas from singleton pregnancies, 279
      (16.5%) were from pregnancies complicated by preeclampsia/eclampsia. Seventy five
      placentas (26.8%) were appropriate for gestational age; other findings included:
      infarcts of various stage and volume in 63 cases (22.6%), minimal hypoxic damage
      in 27 cases (9.7%), accelerated maturation in 42 cases (15.1%), chronic villitis
      in 18 cases (6.5%), mixed findings in 18 cases (6.5%), intervillous thrombosis in
      15 cases (5.4%), sub-choral thrombosis in 9 cases (3.2%), immaturity of the villi
      in 6 cases (2.1%), and findings suggestive of placental insufficiency in 6 cases
      (2.1%). Normal findings were significantly more frequent in the control group
      (P<0.001), but no other significant differences between the groups were found. In
      4 (1.4%) placentas from pregnancies complicated by preeclampsia/eclampsia
      (gestational age 32 to 36 weeks), remnants of endovascular trophoblastic plugs in
      the vessels of the basal decidua were found. CONCLUSION: No significant
      difference was found between the group of placentas from pregnancies complicated
      with preeclampsia/eclampsia and the control group with regard to ischemic changes
      of the placenta. Endovascular trophoblastic plugs in the basal plate vessels from
      the third trimester placentas may play an additional role in the development of
      ischemic lesions in the placentas from pregnancies complicated with
      preeclampsia/eclampsia, but may also simply represent indirect evidence of the
      abnormal expression of certain adhesion molecules in this disorder.

PMID- 15861520
TI  - Bone marrow lymphoid aggregates in malignant lymphomas.
AB  - AIM: To examine the usefulness of molecular analysis of IgH gene rearrangement in
      assessment of clonality in bone marrow biopsies with lymphoid aggregates (LA)
      and/or nodular lymphoid hyperplasia (NLH) in patients with different subtypes of
      malignant lymphomas. METHOD: Five hundred and twenty nine samples of bone marrow
      biopsies, taken in a staging procedure at the time of the initial presentation of
      illness, were processed routinely. Results were grouped in positive, negative,
      and cases with LA or NLH. In 43 samples with present LA/NLH, polymerase chain
      reaction (PCR) analysis of the CDR3 region of immunoglobulin heavy chain gene
      (IgH) for B-cell clonality was performed. RESULTS: Bone marrow malignant lymphoma
      infiltrates were present in 33.8% of lymphoma cases. The incidence of LA/NLH in
      bone marrow was 8.1%. LA/NLH were more frequently found in patients with
      extranodal disease and aggressive subtypes of B cell non-Hodgkin lymphoma (B
      NHL), but there was no significant difference among the incidence according to
      the biological behavior of malignant lymphoma (P=0.232). Results of IgH-CDR3
      region PCR analysis showed a monoclonal pattern in 1 case of Hodgkin lymphoma and
      in 1 control case, an oligoclonal pattern in 2 cases of extra nodal B-NHL,
      whereas all other had polyclonal. CONCLUSION: The results support our initial
      hypothesis that LA/NLH could be differentiated from malignant infiltrates in bone
      marrow staging procedure of malignant lymphoma by topographic pattern and
      histocytomorphology of LA/NLH. Surprisingly, our patients with aggressive B-NHL,
      nodal, as well as extranodal, had LA/NLH in bone marrow biopsies more often than
      patients with indolent B-NHL.

PMID- 15861521
TI  - Endoglin is a better marker than CD31 in evaluation of angiogenesis in
      glioblastoma.
AB  - AIM: To compare endoglin (CD105) and the pan-endothelial marker CD31 in the
      assessment of angiogenesis in glioblastoma and to evaluate their values in the
      prognosis of this malignancy. METHODS: Forty-six cases of glioblastoma were
      included in this retrospective study. All cases were immunohistochemically
      stained for endoglin (CD105), CD31, vascular endothelial growth factor (VEGF),
      and MIB-1 (Ki67). In order to assess microvessel density, positively stained
      microvessels were counted for each specimen in predominantly vascular areas (hot
      spot) at x400 magnification. The intensity of VEGF staining was scored on a three
      tiered scale. The proliferation index was expressed as a percentage of Ki67
      positive cells. RESULTS: Median CD105 microvessel density (median 49
      microvessels/field, range 27-99) was significantly higher than median CD31
      microvessel density (median 37 microvessels/field, range 12-76). CD105
      microvessel density was more closely correlated with VEGF (Spearman's rho=0.421,
      P=0.003) than with CD31 microvessel density (rho=0.330, P=0.024). The
      proliferation index was significantly associated with CD105 microvessel density
      (Pearson's r=0.323, P=0.028), whereas correlation could not be observed with CD31
      microvessel density (r=0.219, P=0.142). Finally, patients with lower CD105
      microvessel density had a longer survival than those with higher CD105
      microvessel density (P=0.045), whereas CD31 microvessel density had no influence
      on the survival time (P=0.340). CONCLUSION: CD105 is a more sensitive marker than
      CD31 in the evaluation of angiogenesis in glioblastoma. Our study is the first
      report of the better prognostic significance of angiogenesis evaluated with CD105
      rather than with CD31 in glioblastoma.

PMID- 15861522
TI  - Easy method of assessing volume of prostate adenocarcinoma from estimated tumor
      area: using prostate tissue density to bridge gap between percentage involvement
      and tumor volume.
AB  - AIM: To determine prostate carcinoma tumor volume in routine pathology practice
      by using prostate tissue density. METHODS: Prostate tissue density was determined
      experimentally by using picnometry in 57 unfixed prostate tissue fragments of
      different size. The percentage of prostate involvement was converted to tumor
      volume using the equation V=m/rho (g/mL). Additionally, all tumor foci were
      outlined in 46 prostates. A high grade component was also designated. The percent
      of prostate involvement by the tumor and separately by the high-grade component
      was determined using the fine grid method (0.9 mm resolution) in all cases.
      Pathologist's estimated square area method was applied for comparison in 27
      cases. All tumor foci were evaluated for Gleason grades. RESULTS: Prostate tissue
      density (rho) was 0.98 or approximately 1.0 (g/mL). Quicker estimated square area
      method was fully comparable to more laborious fine grid method for determination
      of percent of prostate involvement. The percentage of prostate involvement by the
      tumor as measured by the grid method was not significantly associated with the
      Gleason sum of the tumor. However, the total tumor volume that was calculated
      from the percent tumor involvement, mass of the prostate, and tissue density was
      positively associated with the Gleason sum (P=0.035, linear-by-linear
      association). CONCLUSION: Our results show that prostate tissue density can be
      used to determine prostate carcinoma tumor volume in routine pathology practice.

PMID- 15861523
TI  - Volume-related sequence of tumor distribution pattern in prostate carcinoma:
      importance of posterior midline crossover in predicting tumor volume,
      extracapsular extension, and seminal vesicle invasion.
AB  - AIM: To evaluate intraprostatic distribution of prostate carcinoma as a function
      of increasing tumor size and its potential clinical relevance. METHODS: Forty-six
      prostates with different tumor extent were three dimensionally reconstructed and
      analyzed with emphasis on number of separate tumors (multifocality) and its
      distribution on both sides of the urethral midline (laterality). RESULTS: Three
      tumor distribution patterns were identified: multiple bilateral without posterior
      midline crossover, multiple bilateral with crossover, and single bilateral
      (global) tumors. Unilateral tumors were rare (2%). The pattern of tumor
      distribution was associated with total tumor volume, presence and volume of high
      grade component, presence of extracapsular extension, and seminal vesicle
      involvement. Bilateral tumors with crossover were larger than bilateral tumors
      without crossover (Spearman's rho=0,728, P<0.001) and were associated with
      adverse pathological features including capsular penetration, seminal vesicle
      invasion, and surgical margin involvement. However, only high-grade volume was
      independently and highly associated with seminal vesicle involvement (OR=2.64,
      95%, CI=1.181-5.340, P<0.001). Total (OR=2.53 [1.23-3.74], P<0.001) and index
      tumor (OR=2.54 [1.31-4.93], P<0.001) volumes were independently associated with
      capsular penetration. CONCLUSIONS: The distribution of bilateral prostatic
      carcinomas with and without crossover may have clinical relevance because of
      their relation to total and high-grade volume.

PMID- 15861524
TI  - Invasive squamous cell carcinoma of vulva: prognostic significance of
      clinicopathologic parameters.
AB  - AIM: To investigate the prognostic significance of several clinicopathologic
      parameters in patients with invasive squamous cell carcinoma of the vulva.
      METHODS: We retrospectively studied 43 patients with invasive squamous cell
      carcinoma of the vulva treated with radical vulvectomy at the Department of
      Gynecology and Obstetrics at Zagreb University School of Medicine, Croatia, in
      the period from 1978-1996. At the time of analysis, follow-up information was
      obtained for all patients, 18 (41.9%) of whom have died and 25 (58.1%) who were
      alive at the time of the last contact. The mean follow-up time of surviving
      patients was 121 months (range, 6-216 months). Cox proportional hazard analysis
      was performed to examine the prognostic significance of age, menstrual status,
      clinical stage, diameter and localization of the tumor, histological grade,
      nuclear grade, depth of tumor invasion, presence of vascular space invasion,
      tumor growth pattern, presence of lymph node metastasis, DNA ploidy,
      proliferative activity, and mode of therapy. RESULTS: The overall 5-year survival
      for this group of patients was 62.3%. The results of univariate statistical
      analysis confirmed that statistically significant prognostic parameters included
      the age of patients (P=0.038), clinical stage (P=0.001), nuclear grade (P=0.002),
      the depth of tumor invasion (P<0.001), and presence of lymph node metastasis
      (P=0.001). On the other hand, the results of multivariate statistical analysis
      showed that only the depth of tumor invasion (P<0.001) can be considered
      independent, statistically significant prognostic parameter. CONCLUSION: Our data
      suggest that the depth of tumor invasion represents the most important prognostic
      parameter in the group of patients with invasive squamous vulvar carcinoma.
      Clinical significance of DNA ploidy and proliferative activity was not found.

PMID- 15861525
TI  - Curricular reform may improve students' performance on externally administered
      comprehensive examinations.
AB  - AIM: To determine whether changes in the format of teaching pathology and the
      introduction of active learning principles can improve medical students'
      performance on external examinations and enhance clinical skills. METHOD: The
      sophomore Pathology Course at Jefferson Medical College (JMC) in Philadelphia,
      Pennsylvania, USA, was completely restructured in 1986, with greater emphasis
      placed on independent study, small group teaching, and case study discussion. We
      used the scores of JMC medical students on the National Board of Medical
      Examiners (NBME) Part I Examination to compare the performance of JMC students
      who completed their medical education before curricular change (entering classes
      1982-1984) with the performance of subsequent generations of students who were
      taught according to the reformed curriculum (entering classes 1985-1988).
      RESULTS: The two groups of students were comparable in terms of standard social
      and psychometric parameters, such as mean age at matriculation, female/male
      ratio, ratio of minority students in the class, premedical college grade point
      averages, and mean scores on the preadmission Medical College Admissions Test.
      JMC students who studied pathology prior to the curricular reform received on the
      pathology subsection of the NBME Part I Examination reform scores that were close
      to the national average. In contrast, mean scores for students who studied
      pathology after curricular changes were significantly higher than the national
      average (P<0.001). Based on their pathology subscores, the number of JMC students
      scoring below the cutoff line for passing (380 points) decreased significantly
      after the curricular reform, whereas the number of high-scoring students whose
      scores ranked them in the 90th percentile nationally increased. Curricular reform
      was also associated with an increase in overall student satisfaction. CONCLUSION:
      Curricular changes that include an emphasis on active learning can improve the
      performance of medical students on externally administered, objective
      examinations. We have shown that the means of the medical school class can be
      improved, the number of failing students reduced, and the number of high-scoring
      students increased. The improvement of students' scores was not limited to the
      first class after curricular reform, but persisted throughout the entire
      observation period of four years.

PMID- 15861526
TI  - Three years of experience with routine use of telepathology in assessment of
      excisional and aspirate biopsies of breast lesions.
AB  - AIM: To examine the applicability of routine telepathology to accurately diagnose
      breast lesions. METHODS: During a 36 month period, a dynamic telepathology system
      was used to assess 315 excisional biopsies and 209 fine needle aspirates of
      breast lesions submitted by surgeons located 20 km from the hospital. The results
      of the gross and microscopic telepathology diagnoses were compared with final
      microscopic diagnoses. RESULTS: No frozen sections were obtained in 120 of 315
      cases submitted for frozen section due to lack of gross lesion (73/120), a
      papillary lesion or a lesion smaller than 1 cm (22/120), or a gross-only
      diagnosis of a benign process was given (23/120). For frozen sections, the
      microscopic telepathology diagnoses had a sensitivity of 81.6%, specificity of
      100.0%, and diagnostic accuracy of 95.3%. For malignant tumors, the positive
      predictive value was 100.0% and the negative predictive value was 94.0%. For the
      fine needle aspirates, microscopic telepathology diagnoses agreed with
      conventional cytology in 163 of 209 cases. Tissue pathology was available for 109
      of the fine needle aspirate specimens. For these 109 cases, telepathology
      diagnosis of malignancy was shown to have a sensitivity of 91.2% and specificity
      of 100.0%. Malignancy was identified in 8 of 16 cases with an atypia microscopic
      telepathology diagnosis and in 18 of 21 suspicious microscopic telepathology
      diagnoses. CONCLUSION: This long term study demonstrates that the routine use of
      telepathology compares well with conventional microscopy in the assessment of
      both frozen sections and fine needle aspirates of breast lesions.

PMID- 15861527
TI  - Full clinical recovery after topical acyclovir treatment of Epstein-Barr virus
      associated cutaneous B-cell lymphoma in patient with mycosis fungoides.
AB  - Primary cutaneous T- and B-cell lymphomas are a heterogeneous group of diseases
      with varied clinical presentations and prognosis. The use of new molecular,
      histological, and clinical criteria has improved their recognition. Cutaneous B
      cell and T-cell lymphomas are seldom found together in the same patient. Here we
      report a rare case of mycosis fungoides variant of a cutaneous T-cell lymphoma
      (CTCL) which later developed Epstein-Barr virus (EBV) associated cutaneous B-cell
      lymphoproliferative disorder. The patient initially presented with generalized
      erythroderma, extensive plaques, and axillary lymphadenopathy. Histopathology and
      immunophenotyping of her tumor from the right breast nodule revealed a T-cell
      lymphoma consistent with mycosis fungoides. She was initially treated with
      pentostatin, followed by topical mechlorethamine and topical steroids. After
      progression of her mycosis fungoides with worsening diffuse skin lesions on this
      regimen, her treatments were changed to oral bexarotene with an initial partial
      response followed by stable disease. Three years from her initial presentation,
      she developed ulcerated cauliflower-like nodules on her forehead. Biopsy of these
      lesions revealed EBV-positive large- and medium-sized pleomorphic B-cells
      consistent with EBV-driven B-cell lymphoproliferative disorder. She was treated
      with topical acyclovir cream on the involved skin areas while continuing with
      oral bexarotene for mycosis fungoides. Skin lesions gradually diminished and
      totally disappeared after four weeks of topical acyclovir treatment. Bexarotene
      treatment was continued for another year until the mycosis fungoides progressed
      and became wide spread causing her death four and a half years after the initial
      diagnosis. The coexistence of two cutaneous non-Hodgkin lymphomas of different
      lineage in the same patient and the complete clinical response of EBV-related B
      cell cutaneous component to topical acyclovir makes this rare case particularly
      interesting.

PMID- 15861529
TI  - Funding of a medical research institute in a small country: 15 years of Instituto
      de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP)-
      interview conducted by Ivan Damjanov.
AB  - This is an interview with Prof Manuel Sobrinho-Simoes, the Director of the
      Institute of Molecular Pathology and Immunology of the University of Porto
      (IPATIMUP), Porto, Portugal. The interview was prepared for this Pathology
      thematic issue, by Prof Ivan Damjanov, from the University of Kansas School of
      Medicine, Kansas City, Kansas, USA. The interview deals with the funding and the
      growth of IPATIMUP, which became, within 15 years from its inception, one of the
      leading biomedical research institutions of Portugal. The interview touches upon
      the logistical, political, financial, and personnel-related problems they
      encountered during these 15 years. It illustrates some of the dilemmas and
      questions faced by scientists in Porto, which are also relevant to scientists in
      other small countries.

PMID- 15861528
TI  - Malignant blue nevus with lymph node metastases in five-year-old girl.
AB  - We report an unusual case of a malignant blue nevus in a five-year-old girl,
      which turned out to be malignant only after the development of lymph node
      metastases three years after the excision of the primary tumor on the patient's
      cheek. A functional bilateral neck dissection was performed and the patient is
      alive with no evidence of disease 8 years after the excision of the primary skin
      lesion.

PMID- 15861530
TI  - Counting our blessings.

PMID- 15861531
TI  - Health and peace: Galtung's thought experiment.

PMID- 15861532
TI  - Evidence-based emergency medicine/rational clinical examination abstract.
      Physical examination of the liver.

PMID- 15861533
TI  - Evidence-based emergency medicine/rational clinical examination abstract.
      Abdominal palpation for the diagnosis of abdominal aortic aneurysm.

PMID- 15861534
TI  - Detection of genetically modified corn (Bt176) in spiked cow blood samples by
      polymerase chain reaction and immunoassay methods.
AB  - The fate of DNA and protein transgenic sequences in products derived from animals
      fed transgenic crops has recently raised public interest. Sensitive molecular
      tests targeting the Bt176 genetic construct and the transgenic Cry1Ab protein
      were developed to determine whether plant sequences, especially transgenic
      sequences, are present in animal products. A protocol for total DNA extraction
      and purification from cow whole blood samples was first drawn up and assessed by
      spiking with known amounts of DNA from Bt176 maize. The limit of detection for
      transgenic sequences (35S promoter and Bt176-specific junction sequence) was
      determined by both the polymerase chain reaction-enzyme-linked immunosorbent
      assay (PCR-ELISA) and the 5'-nuclease PCR assay. Four additional PCR systems were
      built to substantiate the results. The first detects a mono-copy maize-specific
      sequence (ADH promoter). Two others target multi-copy sequences from plant
      nucleus (26S rRNA gene) and chloroplast (psaB gene). The last one, used as a
      positive control, targets a mono-copy animal sequence (alpha(s1)-casein gene).
      Both methods detected a minimum spiking at 25 copies of Bt176 maize/mL in 10 mL
      whole blood samples. The sandwich ELISA kit used detected down to 1 ng transgenic
      Cry1Ab protein/mL spiked whole blood.

PMID- 15861535
TI  - [Selectively desulfurizing organic sulfur of diesel oil by resting cells].
AB  - Rhodococcus sp. FS-1 ,which can specially break the C[single bond]S bond of
      dibenzothiophene (DBT) and convert DBT into 2-hydrobenzophene by "4S" pathway, is
      used to decrease the sulfur content in diesel oil. This research focuses on the
      diesel oil desulfurization using resting cells of Rhodococcus sp. FS-1. The
      research result indicate that the desulfurization activity of the resting cells
      of Rhodococcus sp. FS-1 was strongly high. When the concentration of DBT was 0.5 
      1.0mmol/L and the ratio of oil/water was 1:5, the effect of desulfurization was
      highest. The desulfurization rate was over 85 % when desulfurizing the diesel oil
      twice. GC analysis proves that this process did not break the carbon-carbon
      backbone. The calorific value of diesel oil is reserved.

PMID- 15861536
TI  - [Isolation and degrading characters of pendimethalin degrading bacteria].
AB  - Microbial degradation of pendimethalin and the effects of culture conditions in
      vitro are studied. Twenty-nine strains are isolated by enrichment from soil and
      sludge. 3 strains can degrade more than 80% of pendimethalin of 100 mg x L(-l) in
      3 days in culture fluid. 2 bacteria are considered as efficiently degrading
      strains identified as Pseudomonas, Mirococcus luteus. The efficiency of
      degradation is affected by culture conditions such as pH, temperature and the
      concentration of sucrose and pendimethanlin. The optimal conditions are proposed.

PMID- 15861537
TI  - Notice of duplicate publication.

PMID- 15861538
TI  - Community of scholars.

PMID- 15861539
TI  - What is a community of scholars in the practice environment?

PMID- 15861540
TI  - A community of scholars.

PMID- 15861541
TI  - A community of scholars.

PMID- 15861542
TI  - Parse's criteria for evaluation of theory with a comparison of Fawcett's and
      Parse's approaches.

PMID- 15861543
TI  - Re: "Theory of Organic Entities".

PMID- 15861544
TI  - Re: Commemoration of the 200th anniversary of the first edition of "Teorya
      Jestestw Organicznych".

PMID- 15861545
TI  - The CPI options: what they are and what they mean for Social Security.

PMID- 15861546
TI  - Microsurgical keyhole approach for middle fossa arachnoid cyst fenestration.

PMID- 15861547
TI  - Transcranial motor evoked potential recording in a case of Kernohan's notch
      syndrome: case report.

PMID- 15861548
TI  - Duration of cognitive impairment after sports concussion.

PMID- 15861549
TI  - Altered arterial homeostasis and cerebral aneurysms: a review of the literature
      and justification for a search of molecular biomarkers.

PMID- 15861550
TI  - Anterior cervical fusion using dense cancellous allografts and dynamic plating.

PMID- 15861551
TI  - The Cinderella disease.

PMID- 15861552
TI  - Dietary treatment proposed for Canavan's disease.

PMID- 15861553
TI  - Modelling of multiple system atrophy in mice.

PMID- 15861554
TI  - Hearing taste and colouring text.

PMID- 15861555
TI  - RNA interference protects against ALS in mouse model.

PMID- 15861556
TI  - Exercise could prevent cerebral changes associated with AD.

PMID- 15861557
TI  - MRI for in vivo detection of amyloid plaques.

PMID- 15861558
TI  - Gene variants affect response to antiepileptic drugs.

PMID- 15861559
TI  - Genetic model predicts stroke in sickle-cell disease.

PMID- 15861560
TI  - Games without frontiers.

PMID- 15861561
TI  - Long-term study proposed for COX2 inhibitors.

PMID- 15861562
TI  - Industry shrugs off NIH consulting ban.

PMID- 15861563
TI  - Cancer drugs could now discover X factor.

PMID- 15861564
TI  - Experimental use provision.

PMID- 15861565
TI  - An audience with... John L. LaMattina.

PMID- 15861566
TI  - BioPharma licensing and M&A trends.

PMID- 15861567
TI  - Azacitidine.

PMID- 15861568
TI  - Effect of pirenzepine ophthalmic solution on form-deprivation myopia in the
      guinea pigs.
AB  - BACKGROUND: Nonselective muscarinic receptor antagonist, atropine, was believed
      to inhibit myopic progression. The purpose of this study was to determine the
      efficacy, through topical administration, of the M1-selective muscarinic
      antagonist pirenzepine in preventing experimentally induced form-deprivation
      myopia in guinea pigs. METHODS: Fifty-three guinea pigs, which underwent
      monocular deprivation with their eyelids sutured, were divided into 6 groups.
      Three groups were treated with 1%, 2% or 4% pirenzepine ophthalmic solutions; the
      fourth group with atropine; the fifth with saline and the last group left
      untreated. Ocular refraction, in vivo biometric measurements and wet eye weight
      were collected before and after the experiment. All the eyes were finally
      enucleated for histopathological examination to evaluate the possible toxic
      effects on ocular structures. RESULTS: Animals untreated or treated with saline
      produced (-2.31+/-1.47) D and (-2.25+/-0.88) D of axial myopia respectively.
      Those treated with 1% pirenzepine ophthalmic solution produced relative myopia of
      (-1.63+/-0.48) D, and those under the treatment of 2% and 4% pirenzepine
      ophthalmic solution only developed a relative myopia of (-0.89+/-0.42) D and (
      0.70+/-0.41) D (F=9.56, P<0.05). The significant reduction in myopia in 2% and 4%
      pirenzepine treated animals was caused by significantly less vitreous chamber
      elongation and axial elongation of the deprived eyes [2% group: (0.009+/-0.052)
      mm, 4% group: (0.006+/-0.078) mm] when compared with untreated, saline treated or
      1% pirenzepine treated guinea pigs (0.057+/-0.056) mm, (0.064+/-0.053) mm and
      (0.033+/-0.035) mm, respectively]. Histological examinations revealed no
      obviously toxic effects on the eyes treated with pirenzepine. CONCLUSION: Topical
      administration of the M1-selective muscarinic antagonist, pirenzepine, can
      prevent induced form-deprivation myopia in guinea pigs by inhibiting axial
      elongation without obvious damage to ocular tissues.

PMID- 15861569
TI  - Law forum.

PMID- 15861570
TI  - The clinical laboratory & infection control. Part 2.

PMID- 15861571
TI  - Managerial requisites for success in data processing.

PMID- 15861572
TI  - Computers: management information for religious.

PMID- 15861573
TI  - Can hospitals "Go it alone " in education?

PMID- 15861574
TI  - Automation in the library.

PMID- 15861575
TI  - Christian formation in the school of nursing.

PMID- 15861576
TI  - Medicare, the bell rings; Title XIX... nine more state plans approved.

PMID- 15861577
TI  - Patient-dietitian relations; a psychological approach.

PMID- 15861578
TI  - Reorganizing a nursing service department.

PMID- 15861579
TI  - Purchase order-check procedure means "in$tant money".

PMID- 15861580
TI  - Weight increase of the thyroid gland as a tentative screening parameter to detect
      the illegal use of thyreostatic compounds in slaughter cattle.
AB  - A total of 45 normal or enlarged thyroid glands of adult slaughter cattle were
      weighed and analyzed by thin-layer chromatography for the presence of residues of
      the following thyreostatic compounds: thiouracil, methylthiouracil,
      propylthiouracil, phenylthiouracil, and methimazole. In 21 glands, mostly from
      imported animals, residues of methylthiouracil or methimazole were detected.
      These thyroids ranged in weight from 68-245 g (mean value 118 g). Glands in which
      no residues were found, varied in weight between 20 and 124 g (mean value 42 g).
      Taking an upper limit of 60 g as normal, 4 out of 22 were false-positive' with
      respect to the 5 thyreostatic compounds screened for, while no false-negative
      cases were scored. On the basis of these results the weight increase of the
      thyroid gland is proposed as a simple indirect parameter in the screening for the
      illegal use of thyreostatic compounds in slaughter cattle.

PMID- 15861581
TI  - Induction of acquired cellular resistance in mice with viable and macrophage
      processed Listeria monocytogenes.
AB  - Intracutaneous immunization of mice with 10(5) or 10(6) viable listeria resulted
      in acquired cellular resistance (ACR) of short duration (7 days). The period
      during which viable Listeria monocytogenes had to be present in order to induce
      ACR was estimated by killing the listeria at different times after immunization
      by injecting the bactericidal antibiotic amoxycillin. The killing of listeria
      within 6 h after injection prevented the induction of A CR completely, between 6
      and 12 h partially, while survival of listeria within animals for at least 18 h
      was required for the induction of complete protection. To determine whether
      multiplication of viable listeria was a prerequisite for the induction of ACR,
      the bacteriostatic antibiotic minocycline was injected for four days after
      immunization. Induction of ACR was only possible if the dose of viable listeria
      was large enough to permit a proportion of the listeria to escape bacteriostasis.
      Interaction of peritoneal macrophages of normal mice and viable listeria yielded
      a supernatant which induced specific ACR in normal recipient mice. No ACR could
      be induced with supernatant obtained from normal macrophages after digestion of
      killed listeria. A reduced level of ACR was obtained with supernatant collected
      after interaction of macrophages from immune mice and viable listeria. The
      immunogenic material present in the supernatant of normal macrophages after
      interaction with viable listeria is thermolabile, has a molecular weight of over
      300,000, and is not affected by treatment with DNase, RNase, or trypsin.

PMID- 15861582
TI  - Effect of Tomanol on the pharmacokinetics and tissue distribution of penicillin G
      in dairy cows.
AB  - Following concomitant intravenous administration of Tomanol and sodium penicillin
      G to six Dutch Friesian dairy cows a significant decrease in total body clearance
      of penicillin (34.7%) and a prolongation of the elimination half-life of
      penicillin (17.2%) was observed. Tomanol did not affect other pharmacokinetic
      parameters such as rate constants of drug transfer (k12/k21, alpha en beta),
      distribution volume of the central compartment (V1), and extrapolated serum drug
      levels. Intravenous or intramuscular administration of Tomanol had no effect on
      the tissue distribution of penicillin G, because neither a change in the ratios
      of muscle to serum and of kidney cortex to serum nor a change in an induced
      steady state level of low penicilline G serum concentrations was observed. From
      the data obtained it is concluded that concomitant Tomanol administration with
      penicillin induces an elevation of the serum penicillin concentration and
      prolongs the persistence of penicillin residues in carcass meat and organs.

PMID- 15861583
TI  - Oral immunization of sows: anti-K88 antibodies in serum and milk of the sow and
      in serum of the piglets.
AB  - Pregnant sows were immunized by oral application of live E. coli. The effect of
      immunization was demonstrated by measuring the titers of anti-K88 antibodies in
      sow serum, colostrum and milk as well as in piglet sera using enzyme-linked
      immunosorbent assays. The isotype involved in anti-K88 reactivity was found to be
      IgA. By comparing IgA-titers in colostrum and milk, the local production of this
      Ig-class in the mammary gland is suggested.

PMID- 15861584
TI  - Pharmacological aspects of chloramphenicol administration by the intramammary
      route to lactating dairy cows.
AB  - Concentrations of chloramphenicol (C M) were determined, by microbiological
      assay, in the milk and blood serum of 17 culled dairy cows after intramammary
      infusion of an approved parenteral CM product (Gloveticol) and in the milk of 16
      lactating cows after treatment with two approved CM products for intramammary
      infusion, at dosages ranging from 1 to 30 g/cow. C M was quickly absorbed from
      the udder into the blood circulation; the doses of 12.5 and 25 g/cow were almost
      completely absorbed within 20 hours. Absorption half-life (t1/2ab) from fully
      functioning quarters was 57+/-18 minutes, and the t1/2ab from partially
      functioning quarters was 125+/-37 minutes. Mean peak serum C M concentrations
      were 6.1, 16.2, and 37.4 microg/ml after the cows had been infused with 5, 12.5,
      and 25 g, respectively. These values were considerably higher than the
      corresponding peak serum C M concentrations reported following intramuscular
      injection of equivalent doses of the drug. C M residues were not detectible
      microbiologically in milk from treated quarters 20 hours after treatment with 5 g
      or 6.25 g, and 36 hours after treatment with 15 g. Drug concentrations in the
      milk from the non-treated quarters were approximately 70 per cent of the
      corresponding serum drug levels. Serum CM concentrations of potential therapeutic
      value in the treatment of gram-negative bacterial infections, i.e. > 5 microg/ml,
      were maintained for 8 hours after cows had been infused with 12.5 g, and for 12
      hours after infusion with 25 g. The implications of the improved systemic
      availability of C M infused by the intramammary route over the intramuscular
      route are discussed in terms of potential therapeutic efficacy, local irritation,
      and duration of drug residues.

PMID- 15861586
TI  - On the ecology of the harbour seal Phoca vitulina in the Wadden Sea: population
      dynamics, residue levels, and management .
AB  - The harbour seal population in the Dutch Wadden Sea decreased significantly
      during the last decades. Calculations based on bounty data revealed that the
      population decreased from about 2700 in 1950 to about 900 in 1959. Annual aerial
      surveys--which were carried out since that time--showed a slight increase due to
      the stop of hunting. However, after 1964 a new decline occurred and since 1974
      the population stays at a level of about 450 specimens. During 1974 to 1978 the
      population dynamics of the population have been studied Frequent aerial surveys
      provided data on the size of the population. These data have been used in a
      simulation model and the birth rate and the initial juvenile mortality were
      calculated. During boat trips an indication of the age composition was obtained
      by measuring track widths. By comparing these results with similar results from a
      stable population in Schleswig Holstein it appeared: (1) that juvenile mortality
      in the first weeks in the Dutch population is higher than that in Schleswig
      Holstein but the overall mortality of pups in both areas in their first three
      months of life is of the same order; (2) that pup production in the Dutch
      population is low compared to the population in Schleswig Holstein; (3) that
      apparently immigration from elsewhere occurs. To investigate the contribution of
      environmental pollution to the decline of the Dutch seal population tissues of
      dead, stranded animals originating from Schleswig Holstein, Denmark and the
      Netherlands were collected and analyzed for PCBs, o,p'-DDT, p,p'-(DDT, DDE, TDE),
      dieldrin, aldrin, endrin, endosulfan, alpha, beta, gamma,-HCH, HCB, QCB
      (pentachlorobenzene), HEPO, total mercury, methyl-mercury, selenium and bromium.
      Considering epidemiological and experimental data on the effects of PCBs on
      mammalian reproduction, strong support is obtained for the hypothesis that PCBs
      are responsible for the decreased reproduction in seals from the Dutch Wadden
      Sea. if PBCs are responsible for the decrease of the Dutch seal population,
      measure of all North Sea countries are urgently required because these PCBs may
      not only be a hazard to seals but also to other animals and even man. Production
      and use of PCBs should be limited and used PCBs should be collected and
      destroyed. However, even if an immediate ban on PCB's would be effected, the
      effects of PCBs because of their persistent character are likely to last many
      years. For that reason it may be assumed that the seal population in the western
      Wadden Sea still faces a difficult period in the years to come. In order to lead
      this population through this difficult period, all possible measures enhancing
      its continued existence should be taken. Since the seals in the Wadden Sea form
      one population maximum result may be expected from measures applying to all seals
      in the Wadden Sea. Thus international cooperation is necessary. The following
      measures are proposed: Continued interdiction of hunting in order to obtain a
      maximum number of animals taking part in reproduction. Establishment of seal
      reserves and, additionally supporting seal nursery stations in order to guarantee
      a maximum reproductive output. However, it has to be stressed that these measures
      are not effective if at the same time the main cause of the decrease is not found
      and brought under control.

PMID- 15861585
TI  - Host parasite relationships in Trypanosoma (duttonella) vivax with special
      reference to the influence of antigenic variation.
AB  - A mouse model system was used to study various aspects of host and parasite
      relationships in Trypanosoma vivax infections. These included the phenomenon of
      antigenic variation, the variable parasite antigens responsible for this
      phenomenon, parasite-host adaption, host immune responses and the role of genes
      in the major histocompatibility complex in the control of infection. While the
      mouse model system has allowed investigation of these aspects of host parasite
      relationships, it is clear that the system is much more limited than those
      generally used in T. brucei spp and T. congolense infections. This is indicated
      by the discovery that not all VATs of T. vivax were equally infective for mice,
      though in some cases infectivity could be improved by bovine serum
      supplementation and/or immunosuppression of the mouse host. In the case of rats,
      infection was even restricted to a smaller number of the VATs studied. It was,
      however, possible to biochemically characterize the variable surface antigen
      carried by T. vivax and show its similarity to those carried by T. brucei and T.
      congolense. The H-2 complex was found not to influence acquired resistance of
      inbred strains. Cyclic transmissions of T. vivax infections to goats combined
      with chemotherapy were carried out in an attempt to induce protection to
      subsequent infection as has been shown in T. brucei and T. congolense infections.
      Such protection could, however, not be obtained, The failure of the metacyclic
      VATs to induce immunity, was perhaps due to rapid decrease in antibody titres to
      bloodstream VATs found after treatment and prior to rechallenge. The usefulness
      of the mouse model system in elucidating the mechanisms responsible for the non-H
      2 linked differences in susceptibility to T. vivax infections should be further
      explored and its relevance to mechanisms of trypanotolerance in domestic
      ruminants defined.

PMID- 15861587
TI  - Freezing mouse blastocysts. The influence of the preparations prior to freezing
      on the survival rate of the blastocysts.
AB  - A good survival rate in culturing mouse blastocysts can be obtained in Ovum
      Culture Medium, enriched with 20 per cent inactivated Foetal Bovine Serum or
      Sheep Serum under air. The transfer of fresh blastocysts gives the best results
      if the recipients are on day 3 of the pseudo-pregnancy, but with 20 hours'
      cultured blastocysts it is better to use recipients on day 4. Exposure to 1.5 M
      DMSO has no harmful effect, provided that the DMSO is added at 5 degrees C in 6
      steps and is removed, again in 6 steps, at 35 degrees C. The crystallization of
      the medium containing the embryos at -5 degrees C to -6 degrees C doet not appear
      te have a harmful influence on culture results of the blastocysts.

PMID- 15861588
TI  - Superovulation in mice in relation to their age.
AB  - Superovulation in mice is most likely to be successful if they are treated at the
      age of 20-32 days. Both the number of ovulations and the quality of the embryos
      are significantly better in comparison with superovulated older mice (32-60
      days). In this investigation the production of normally developed embryos in
      young mice of 20-32 days old was 28.7 per superovulated animal and 11.3 or 14.0
      in the groups of older mice respectively (32-46 days and 46-60 days).

PMID- 15861589
TI  - Benign cementoblastoma: a case report.
AB  - Benign cementoblastoma is an odontogenic tumour of mesenchymal origin. It usually
      presents as a distinct lesion with characteristic radiographic and
      histopathologic features. The tumour is attached to the roots of the teeth and
      commonly occurs in the posterior mandible. The case of a 19-year old female with
      a benign cementoblastoma is presented. The clinical histopathologic and
      therapeutic aspects of the tumour are described.

PMID- 15861590
TI  - Orthodontic/restorative interface: the multidisciplinary management of a severely
      compromised adult dentition. A case report .

PMID- 15861591
TI  - Surgically assisted rapid palatal expansion for management of transverse
      maxillary deficiency.
AB  - Surgically assisted rapid palatal expansion (SA-RPE) is a combined orthodontic
      and surgical procedure which facilitates an increase in transverse maxillary
      width in skeletally mature adults. Many different techniques have been described.
      In 1992 Pogrel and associates described a conservative method of widening the
      maxilla. This procedure consisted of bilateral zygomatic buttress and midpalatal
      osteotomies combined with the use of a tooth-borne device postoperatively. Other
      moreradical SA-RPE procedures have been described in which more extensive
      osteotomies have been performed. Experience of SA-RPE using the simplified
      technique described by Pogrel et al is describe.

PMID- 15861592
TI  - Preparing children for surgery.

PMID- 15861593
TI  - Respite for children with complex health needs: issues from the literature.

PMID- 15861594
TI  - Quality assessment in children's hospice care.

PMID- 15861595
TI  - High dependency care: a model for development.

PMID- 15861596
TI  - Volunteering: serious fun.

PMID- 15861597
TI  - Jehovah's Witness children: when religion and the law collide.

PMID- 15861598
TI  - Tracheostomy management.
AB  - Even though care of children with tracheostomies may differ between hospitals,
      there are basic principles and procedures that all nurses should be aware of
      including how to respond in an emergency.

PMID- 15861599
TI  - Viagra, Levitra, and Cialis: what's the difference?

PMID- 15861600
TI  - Whither PACs?

PMID- 15861601
TI  - Pulmonary lymphangioleiomyomatosis in a postmenopausal woman: case report with
      review of literature.
AB  - Lymphangioleiomyomatosis (LAM) is a rare disorder that occurs almost exclusively
      in young females and characterized by peribronchial, perivascular, and
      perilymphatic non-neoplastic proliferation of smooth-muscle cells. These changes
      may precipitate chylous effusions, pulmonary hemorrhage, bronchial cyst
      formation, progressive loss of lung function, and ultimately death. Most patients
      die within eight to ten years of the time of diagnosis. We report a rare case
      ofpost-menopausal onset pulmonary lymphangioleiomyomatosis in a 62-year old
      Caucasian female that was diagnosed at age 53 and responded well to intramuscular
      injections of Depo-Provera and bilateral oophorectomy. No symptom progression or
      pulmonary function test deterioration was noted over an eight year period of
      clinical follow-up. Our case is unique because of the postmenopausal onset and
      the unusual clinical course of the disease.

PMID- 15861602
TI  - Microscopic colitis: a report of two cases.
AB  - Microscopic colitis is characterized by chronic, watery, secretory diarrhea, with
      a normal or near-normal gross appearance of the colonic mucosa. Biopsy is
      diagnostic and usually reveals either lymphocytic colitis or collagenous colitis.
      The symptoms of collagenous colitis appear most commonly in the sixth decade.
      With collagenous colitis, the major microscopic characteristic is a thickened
      collagen layer beneath the colonic mucosa, and with lymphocytic colitis, an
      increase number of intraepithelial lymphocytes. Clinically, collagenous colitis
      is characterized by long-standing diarrhea. In patients with lymphocytic colitis,
      the duration of diarrhea is usually shorter and female predominance is less
      apparent. We report two cases of lymphocytic colitis in elderly women. Both
      presented with watery diarrhea of two month duration and weight loss. Extensive
      investigations were done and several medications failed to stop their diarrhea.
      Biopsy revealed lymphocytic colitis. Their diarrhea responded well to
      cholestyramine.

PMID- 15861603
TI  - Ministers warned: nurses' stress at a 'dangerous level'.

PMID- 15861604
TI  - Preparing for a pandemic.

PMID- 15861605
TI  - Assessing mental health needs.

PMID- 15861606
TI  - Emergency care in Wales.

PMID- 15861607
TI  - Board's eye view.

PMID- 15861608
TI  - In the media spotlight.

PMID- 15861609
TI  - Bridging the gap.

PMID- 15861610
TI  - A nose for trouble.

PMID- 15861611
TI  - Patient centred care: lessons from the medical profession.

PMID- 15861612
TI  - Appropriate categorisation of mild pain at triage: a diagnostic study.

PMID- 15861613
TI  - The convergent validity of the Manchester Pain Scale.
AB  - OBJECTIVE: To test the convergent validity of the Manchester pain scale when
      compared to the current 'gold standard' in children's pain assessment, the Oucher
      pain scale. METHOD: One hundred and fifty two children presenting to the
      emergency department had pain scale assessments using both the Manchester and
      Oucher pain scales. The order of presentation of the scales was randomised. The
      degree of convergence between the scales was assessed using Spearman's rank
      correlation as well as Bland and Altman plots. RESULTS: One hundred and thirteen
      children used numerical scales; the correlation coefficient for these was 0.802.
      Thirty nine children used pictorial scales; the correlation coefficient was
      0.820. CONCLUSION: There is strong convergent validity between the scales as
      demonstrated by a high degree of correlation between the numerical and pictorial
      scores generated by the Manchester and Oucher pain scales. The Manchester pain
      scale can be used to assess pain in children presenting to emergency departments.

PMID- 15861614
TI  - Secondary prevention interventions for young drug users: a systematic review of
      the evidence.
AB  - This paper reviews the international scientific evidence on the effectiveness of
      secondary prevention interventions for young drug users. The review provides
      insight into the effectiveness of interventions that have been evaluated using
      moderately strong research designs. Most of the studies included are from the
      United States of America. Some interventions are effective in reducing drug use
      and associated problems while others have no or mixed effect. Those successful in
      reducing drug use include behavior therapy, Minnesota 12-step programs,
      residential care, and general drug treatment. Those with either no effect or
      mixed effect include schools interventions. Involving parents and other agencies
      may enhance an intervention's effect. There is a lack of good quality studies
      outside the USA. Future interventions should focus on either low- or high-risk
      groups of young drug users. Future research should be conducted on a wider range
      of services for young people and include non-medical outcomes such as
      communication skills, schooling, employment, family relations, and economic
      costs.

PMID- 15861615
TI  - Level of functioning and recidivism risk among adolescent offenders.
AB  - The assessment of offending youth is important in determining the most
      appropriate disposition for adolescents involved in the justice system. Recent
      studies have found a relationship between justice system involvement and level-of
      functioning (LOF). This study investigated the relationship between LOF and
      recidivism risk among adolescents involved in a community-based, juvenile justice
      treatment program. The results document that conceptually similar domains are
      substantively correlated; however, a range of functioning was found among youth
      considered to have the same risk of recidivism. Overall, the results suggest that
      LOF measures may be associated with risk measures due to a convergence of areas
      assessed and that the two constructs also may have a relationship analogous to
      LOF and clinical diagnosis.

PMID- 15861616
TI  - Stress, self-esteem, and suicidal ideation in late adolescents.
AB  - The relationships among stress, self-esteem, and suicidal ideation in late
      adolescents were examined in a group of college students. Multiple regression
      analysis indicated that both stress and self-esteem were significantly related to
      suicidal ideation; low self-esteem and stressful life events significantly
      predicted suicidal ideation. The hypothesis that self-esteem would moderate the
      effects of life stressors on suicidal ideation was supported at the .06 level. A
      significant minority of the sample indicated having thoughts severe enough to be
      classified as clinical suicidal ideation. In general, participants who had
      experienced negative life events in the 6 to 12 months prior to participating in
      the study had lower self-esteem than those who had similar stresses within the
      prior six months. However, the opposite was true for clinical suicidal ideators;
      those who experienced negative life stressors recently had lower self-esteem than
      those who experienced negative life events six months to a year in the past.

PMID- 15861617
TI  - Effect of socioeconomic status on general and at-risk high school boys'
      willingness to accept same-sex peers with LD.
AB  - Thirty-eight educationally successful and 33 educationally at-risk high school
      boys from varying SES backgrounds participated in a study to determine their
      willingness to allow same-sex peers with LD to participate in activities in the
      school, out-of-school, and both contexts. Kruskal Wallis One-way Analysis of
      Valance of Ranks results indicated that, regardless of academic designation, boys
      from low SES backgrounds were more willing than their counterparts to accept
      peers with LD. Significant differences among SES groups were found in several
      activities performed in the out-of-school contexts, especially those with
      emotional or cognitive connotations. Discussion addresses the importance of
      training classroom teachers and general education students in maintaining an
      inclusive environment.

PMID- 15861618
TI  - The relationship between out-of-school activities and positive youth development:
      an investigation of the influences of communities and family.
AB  - There is growing evidence that participation in constructive leisure activities
      facilitates positive youth development. Empirical evidence also supports the
      influence of families and communities on positive developmental outcomes for
      adolescents. This study examined the relationship among attitudes toward family
      and community, participation in structured out-of-school activities, and pro
      social behavior. As predicted, community aspects such as opportunities available
      and the attitudes the youth held toward the community, as well as their attitude
      toward family were predictive of activity involvement. Activity involvement, in
      turn, was predictive of pro-social behavior. Attitude toward family was also
      predictive of attitude toward the community. Attitude toward community was a
      direct predictor of the positive developmental outcome of pro-social behavior,
      although contrary to the original hypothesis, family influences did not have a
      direct effect on pro-social behavior. Implications for continued practice and
      change for a variety of sectors in the positive youth development field such as
      educators and educational institutions, youth-serving organizations, families,
      and policy makers are discussed, along with recommendations for continued
      research in this field.

PMID- 15861619
TI  - Alcohol use and depression among African-American and Caucasian adolescents.
AB  - The purpose of this study was to determine differences in reported alcohol use
      and depressive symptomatology among a sample of 524 African-American and
      Caucasian adolescents. Of specific interest was determining if ethnicity, gender,
      and age predicted severity of scores obtained on the Reynolds Adolescent
      Depression Scale (RADS) and Adolescent Drinking Index (ADI). Extreme groups were
      formed using upper (> 75%) and lower (< 25%) quartiles. Three other groups were
      formed using each instrument's normatively derived cutoff scores: depressed only
      (RADS > 77), heavy drinking (ADI > 16) and mixed (RADS > 77, ADI > 16). Several
      results were obtained. First, Caucasians obtained significantly higher scores on
      the ADI than African-Americans, although no differences were obtained for the
      RADS. Females scored higher on the RADS but lower on the ADI than males. In terms
      of extreme scores, females were less likely to belong to the severe depression
      group, while older adolescents in general and African-Americans in particular had
      a greater probability of belonging to the heavy-drinking group. Finally, using
      RADS and ADI cutoff scores, females were less likely than males to belong to the
      depression only group as were African-Americans. Older adolescents, in general,
      and African-Americans in particular had a greater probability of belonging to the
      mixed group than did their counterparts.

PMID- 15861620
TI  - The relationship between social anxiety and social support in adolescents: a test
      of competing causal models.
AB  - This study compared the strength of competing causal models in explaining the
      relationship between perceived support, enacted support, and social anxiety in
      adolescents. The social causation hypothesis postulates that social support
      causes social anxiety, whereas the social selection hypothesis postulates that
      social anxiety causes social support. The reciprocal model combines the two
      hypotheses by arguing that the causal relationship between social support and
      social anxiety is largely reciprocal. This study tests a modification of the
      reciprocal model by specifying perceptions of support as a mediating construct.
      Two waves of data with an interval of three months were collected on 357 college
      students. Structural equation modeling was used to compare the reciprocal and
      mediated reciprocal causal models. The study found some support for the mediated
      reciprocal model, but the magnitude of the relationships were weaker than
      expected. Limitations and suggestion for future research are discussed.

PMID- 15861621
TI  - Media influences on body image and disordered eating among indigenous adolescent
      Australians.
AB  - There has been no previous investigation of body image concerns and body change
      strategies among indigenous Australians. This study was designed to investigate
      the level of body satisfaction, body change strategies, and perceived media
      messages about body change strategies among 50 indigenous (25 males, 25 females)
      and 50 non-indigenous (25 males, 25 females) Australian adolescents (mean age
      14.05, SD = 1.05). Consistent with past studies, girls were more likely to be
      dissatisfied with their weight and engage in strategies to lose weight. However,
      contrary to expectations, indigenous adolescents engaged in more strategies to
      lose weight, increase weight, and increase muscles than did non-indigenous
      adolescents, despite perceiving fewer media messages about losing weight.
      Additional factors that may explain the findings and the need for further
      research with different cultural groups are highlighted.

PMID- 15861622
TI  - Attachment and motivational strategies in adolescence: exploring links.
AB  - Within the framework of attachment theory and of motivation goal theory, this
      study explored the relation between quality of attachment strategies and quality
      of motivational strategies in a sample of young adolescents. Specifically, this
      study examined patterns of thoughts, behaviors, and emotions as they related to
      representations of attachment and motivational functioning in situations that
      challenge or threaten three psychological needs (emotional security, competence,
      and autonomy). Forty-four students, aged 11 to 14 years, responded to imagined
      stressful situations in order to: (a) assess attachment strategies; (b) identify
      and assess students' motivational strategies in stressful classroom
      circumstances; (c) assess motivational strategies of students with high and low
      control and agency beliefs; and (d) examine the relations between attachment and
      motivational strategies. Four distinct action patterns were identified: flexible
      action, rigid action, passive behavior, and disorganized behavior. Significant
      relations were found between control beliefs and motivational strategies, as well
      as a trend toward relations between attachment and motivational strategies,
      suggesting that secure adolescents show more constructive motivational strategies
      and less disorganized strategies when compared to insecure adolescents.

PMID- 15861623
TI  - Male adolescents' reasons for participating in physical activity, barriers to
      participation, and suggestions for increasing participation.
AB  - This study explored male adolescents' reasons for participating in moderate and
      vigorous physical activity, perceived barriers to moderate and vigorous physical
      activity, and suggestions as to what can be done to increase participation in
      physical activity. A total of 26 male 15- and 16-year-old adolescents
      participated in focus group sessions, which were audiotaped and transcribed
      verbatim; qualitative software facilitated data analysis. A constant comparison
      approach was used to inductively develop themes. It was found that participants
      engaged in physical activity for both intrinsic and extrinsic reasons. Their
      perceived barriers to physical activity included both internal factors
      (individual characteristics, lower priority for physical activity, and
      involvement in technology-related activities) and external factors (the influence
      of peers and family, lack of time, and inaccessibility and cost of facilities).
      Participants suggested that physical activity be promoted more in the community
      and that an environment more supportive of physical activity be developed.
      Results suggest that a variety of strategies should be used to help male
      adolescents maintain or increase participation in moderate and vigorous physical
      activity.

PMID- 15861624
TI  - HIV/AIDS in South Africa: a review of sexual behavior among adolescents.
AB  - South Africa has a fast-growing HIV/AIDS rate, with the highest prevalence among
      young people (15 to 24 years), especially females. This paper is a comprehensive
      analytical review of available research concerning the sexual behavior of
      adolescents in South Africa. It offers insight into HIV infection among
      adolescents and provides an important base for educational interventions aimed at
      behavior change and reducing further transmission. The most important conclusion
      is that, despite the research (however limited) that has been done, there has
      been no significant change in the rate of infection among adolescents in South
      Africa. A new generation of behavioral interventions, involving both factual
      knowledge and life skills to promote behavioral risk reduction, is recommended.

PMID- 15861625
TI  - The influence of violent behavior and victimization at school on psychological
      distress: the role of parents and teachers.
AB  - This study examined the role of adolescents' interactions with both parents and
      teachers in the relationship between violent behavior/victimization at school and
      adolescent psychological distresss (depression and stress). Participants were 983
      Spanish adolescents (mean age 13.7 years) from four public schools in the
      Valencian Community. Statistical analyses were carried out using structural
      equation modeling. Results showed victimization to be directly and positively
      related to psychological distress. Moreover, victimization was associated with
      negative father-adolescent communication, which mediated a part of the influence
      of victimization on distress. Regarding school-based violent behavior, no direct
      effect on psychological adjustment was found. Results showed, however, an
      indirect effect: violent behavior negatively influenced communication with
      parents and interaction with teachers which, in turn, was related to poor
      psychological adjustment. This model accounted for 47.7% of the variance in
      psychological distress. Findings are discussed in relation to previous research
      on adolescent psychosocial adjustment, and directions for future research are
      suggested.

PMID- 15861626
TI  - Early school leaving in the lower vocational track: triangulation of qualitative
      and quantitative data.
AB  - This study assessed the reasons for very early school leaving of boys in the
      lower secondary vocational track. A unique combination of quantitative and
      qualitative data from different sources provided background data on these boys
      from a national cohort study on their elementary and high school periods. In
      depth interviews in which the boys reflect on their early school leaving were
      conducted. Four case studies are presented in which the boys' own reflections are
      interpreted in light of the cohort data. It was found that several factors
      contribute simultaneously to early school leaving; however, the emphasis lies
      with learning problems, lack of motivation, and problems arising from choosing
      the wrong vocational track. Specific personal problems also negatively affect the
      school career. While the boys do not feel alienated from school, they do not
      enjoy studying and would rather start work. This approach of combining data
      appears to be worth reproducing.

PMID- 15861627
TI  - An exploration of Taiwanese adolescents' impulsive buying tendency.
AB  - The purpose of this study was to examine via a questionnaire the personal
      characteristics and impulsive buying tendencies of 15- to 19-year-old Taiwanese
      adolescents. Results indicated that the impulsive buying was significantly
      associated with gender, age, and amount of pocket money available. Females
      indicated more impulsive buying than did males, and gradually increased with age.
      Impulsive buying significantly increased with the increase in the amount of
      pocket money available. Possible extensions of the research in this area are
      offered.

PMID- 15861629
TI  - [Mucosal immunology].

PMID- 15861628
TI  - [Microbial recognition mechanism in innate immune system].

PMID- 15861630
TI  - [Chemotaxis of inflammatory cells].

PMID- 15861631
TI  - [Dendritic cells and infection].

PMID- 15861632
TI  - [Regulation of lymphocyte activation and function by cell surface molecules].

PMID- 15861633
TI  - [Mechanism of Th2 cell differentiation and regulation of Th1/Th2 balance].

PMID- 15861634
TI  - [New era of tumor immunotherapy].

PMID- 15861635
TI  - [T cell immunity in autoimmune disease].

PMID- 15861636
TI  - [Signaling mechanisms in innate immunity].

PMID- 15861637
TI  - [Cell surface lectins].

PMID- 15861638
TI  - [Alpha1-proteinase inhibitor: structure and functions].

PMID- 15861639
TI  - [Alpha1-acid glycoprotein: structure and functions].

PMID- 15861640
TI  - [Important role of the lectin complement pathway].

PMID- 15861641
TI  - [Biological function of Toll-like receptors].

PMID- 15861642
TI  - [Recognition of microbes via Toll-like receptors (TLRs)].

PMID- 15861643
TI  - [Signal transduction of Toll-like receptors].

PMID- 15861644
TI  - [Monocytes and macrophages--multifaced cell population involved in inflammation,
      atherosclerosis, and obesity].

PMID- 15861645
TI  - [Dendritic cells].

PMID- 15861646
TI  - [B cells].

PMID- 15861647
TI  - [Helper T cells].

PMID- 15861648
TI  - [Cytotoxic T lymphocytes].

PMID- 15861649
TI  - [Gamma-delta T cells].

PMID- 15861651
TI  - [NK cells and NKT cells].

PMID- 15861650
TI  - [Regulatory T cells].

PMID- 15861652
TI  - [Mast cells].

PMID- 15861653
TI  - [Cytokines and their functions].

PMID- 15861654
TI  - [Cytokine receptors and signal transduction].

PMID- 15861655
TI  - [Class I cytokines (interleukin-2-7, interleukin-9, interleukin-11, interleukin
      12, interleukin-13, interleukin-15, granulocyte-macrophage colony-stimulating
      factor, granulocyte-colony stimulating factor, erythropoietin)].

PMID- 15861656
TI  - [Class II cytokine receptors and their ligands].

PMID- 15861657
TI  - [TNF family (TNF alpha, beta, FasL, CD40L)].

PMID- 15861658
TI  - [Receptor tyrosine kinases (c-kit, c-fmns, Flt-3, Tie2, etc.)].

PMID- 15861659
TI  - [TGF-beta family (TGF-beta, activin, BMP)].

PMID- 15861660
TI  - [Chemokines (IL-8, MCAF/MCP-1, RANTES, MIP-1 etc.)].

PMID- 15861661
TI  - [IL-1 family (IL-1alpha/beta, IL-1Ra, IL-18), IL-16, IL-17].

PMID- 15861662
TI  - [Structures and functions of antibodies].

PMID- 15861663
TI  - [B cell development and Ig gene rearrangement].

PMID- 15861664
TI  - [Molecular mechanisms of antibody generation].

PMID- 15861665
TI  - [Origin of antibody diversity].

PMID- 15861666
TI  - [Complement system in host defense].

PMID- 15861667
TI  - [Activation pathway of complement (classical, alternative, lectin)].

PMID- 15861668
TI  - [Complement regulatory proteins].

PMID- 15861669
TI  - [Self- and non-self recognition mechanism via the complement system].

PMID- 15861670
TI  - [Mechanisms of antigen processing].

PMID- 15861671
TI  - [HLA gene region and its diversity].

PMID- 15861672
TI  - [MHC class II restricted antigen presentation].

PMID- 15861673
TI  - [Antigen presentation mediated by class I major histocompatibility complex].

PMID- 15861674
TI  - [Cross-presentation pathway].

PMID- 15861675
TI  - [Structure and function of TCR].

PMID- 15861676
TI  - [B cell receptor signal transduction].

PMID- 15861677
TI  - [Co-stimulation signals in B cell maturation and activation].

PMID- 15861678
TI  - [Signaling pathway through T cell receptor].

PMID- 15861679
TI  - [Activation of T cells by co-stimulation].

PMID- 15861680
TI  - [Th and Tc cell development--from naive to memory cells].

PMID- 15861681
TI  - [Th1/Th2 differentiation].

PMID- 15861682
TI  - [Development of immune memory--B cells].

PMID- 15861683
TI  - [Mechanisms for generation and maintenance of memory CD8 T cells].

PMID- 15861684
TI  - [Central tolerance].

PMID- 15861685
TI  - [Peripheral tolerance].

PMID- 15861686
TI  - [Oral tolerance].

PMID- 15861687
TI  - [Physiological and pathological roles of apoptosis].

PMID- 15861688
TI  - [Machinery of programmed cell death].

PMID- 15861689
TI  - [Immune anergy in T cell signaling].

PMID- 15861690
TI  - [Immune regulation by regulatory T cells].

PMID- 15861691
TI  - [Immune regulation by Fc receptors].

PMID- 15861692
TI  - [Molecular mechanisms regulating trafficking of immune-competent cells: role of
      cell adhesion molecules].

PMID- 15861693
TI  - [Role of chemokines and chemokine receptors in leukocyte trafficking].

PMID- 15861694
TI  - [Host defence mechanisms offered by the mucosal immune system].

PMID- 15861695
TI  - [Physiological function of intestinal intraepithelial gamma-delta T lymphocytes].

PMID- 15861696
TI  - [Immune responses in intestinal mucosa].

PMID- 15861697
TI  - [Mucosal vaccine].

PMID- 15861698
TI  - [Molecular mechanism of host response to bacterial infection].

PMID- 15861699
TI  - [Role of memory T cells in infectious disease].

PMID- 15861700
TI  - [Viral infection and innate immunity].

PMID- 15861701
TI  - [Herpesvirus infection].

PMID- 15861702
TI  - [Chronic Epstein-Barr virus infection].

PMID- 15861703
TI  - [Immunological aspects of human retrovirus infection].

PMID- 15861704
TI  - [Allergy in parasitic infections].

PMID- 15861705
TI  - [Influenza-associated encephalopathy].

PMID- 15861706
TI  - [Human cytomegalovirus infection].

PMID- 15861708
TI  - [Emerging and re-emerging infectious diseases].

PMID- 15861707
TI  - [Rhinovirus and airway allergy].

PMID- 15861709
TI  - [TGF-beta signaling and carcinogenesis].

PMID- 15861710
TI  - [Regulation of antitumor immunity by controlling immune balance].

PMID- 15861711
TI  - [Identification of human tumor antigens recognized by T cells].

PMID- 15861712
TI  - [Tumor specific antigen and cytotoxic T lymphocytes].

PMID- 15861713
TI  - [Clinical application of NKT cell system for lung cancer].

PMID- 15861714
TI  - [HLA-restricted cancer-specific killer T cells].

PMID- 15861715
TI  - [Present status and perspectives of tumor markers].

PMID- 15861716
TI  - [Immunophenotyping by cell surface marker analysis in hematological disorders].

PMID- 15861717
TI  - [Peptide-based vaccine therapy for cancer patients].

PMID- 15861718
TI  - [Anti-cancer monoclonal antibody].

PMID- 15861719
TI  - [RNA-loaded dendritic cells].

PMID- 15861720
TI  - [HLA mismatch and graft rejection].

PMID- 15861721
TI  - [Organ transplantation and immune response].

PMID- 15861722
TI  - [Immunological tolerance and chimerism--past, present, future].

PMID- 15861723
TI  - [CD25+ CD4+ regulatory T cells maintaining immunological tolerance].

PMID- 15861724
TI  - [The HLA system and transplantation].

PMID- 15861725
TI  - [Xenogeneic organ transplantation].

PMID- 15861726
TI  - [Heart transplantation].

PMID- 15861727
TI  - [Liver transplantation].

PMID- 15861728
TI  - [Lung transplantation].

PMID- 15861729
TI  - [Small bowel transplantation].

PMID- 15861730
TI  - [Hematopoietic stem cell transplantation].

PMID- 15861731
TI  - [Islet cell transplantation].

PMID- 15861732
TI  - [ABO-incompatible kidney transplantation].

PMID- 15861733
TI  - [Monitoring of allograft rejection].

PMID- 15861735
TI  - Patient perspective.

PMID- 15861734
TI  - Things are not always as they seem.

PMID- 15861736
TI  - The best job around.

PMID- 15861737
TI  - Adolescent mental health.

PMID- 15861738
TI  - The future of general practice.

PMID- 15861739
TI  - Presentations of diarrhoea in Australian general practice.
AB  - The BEACH program, a continuous national study of general practice activity in
      Australia, gives us an overview of the consultations in general practice
      involving a patient presentation of diarrhoea. This provides a backdrop against
      which articles in this issue of the Australian Family Physician can be further
      considered.

PMID- 15861740
TI  - Irritable bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) a common worldwide problem,
      particularly women, and presents from the teenage years onward. OBJECTIVE: This
      article discusses the causes, diagnosis and management of IBS. DISCUSSION:
      Disturbed motility and sensory function underlie much of the disturbance in
      function that, not infrequently, begins following an episode of gastroenteritis.
      There is an intimate role for the brain-gut axis in modulating symptoms relating
      to underlying causes of small bowel bacterial overgrowth, food intolerance and
      sensitivity, and abnormalities of corticotropin releasing factors. Management
      requires long term involvement with the patient as there is no single therapeutic
      strategy that is predictably effective. However, diet, bulking agents,
      antispasmodics and a variety of alternative therapies including herbs,
      probiotics, and psychological intervention are important in individual patients.

PMID- 15861741
TI  - Acute gastroenteritis in children.
AB  - BACKGROUND: Gastroenteritis (GE) is inflammation of the mucous membranes of the
      gastrointestinal tract, and is characterised by vomiting and/or diarrhoea. The
      most common causes are viruses, but bacterial, protozoal and helminthic GE occur,
      particularly in developing countries. Vomiting and diarrhoea can be nonspecific
      symptoms in children, and the diagnosis of viral GE should be made after careful
      exclusion of other causes. OBJECTIVE: This article outlines the assessment and
      management of children with acute GE. DISCUSSION: The most important complication
      of GE is dehydration. The amount of weight loss as a percentage of normal body
      weight provides the best estimate of degree of dehydration. Clinical signs are
      not present until the child has lost at least 4% of their body weight. The best
      signs for identifying dehydration include decreased peripheral perfusion,
      abnormal skin turgor, and an abnormal respiratory pattern. Fluid replacement is
      the mainstay of management and most infants and children can be rehydrated safely
      with oral rehydration solution. Antiemetics and antidiarrhoeals are not indicated
      in children with acute GE.

PMID- 15861742
TI  - Inflammatory bowel disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is increasing in frequency in
      Australia. General practitioners play an important role in early diagnosis and in
      a multidisciplinary approach to managing such patients. Keeping abreast of
      evolving concepts, particularly in treatment, is challenging. OBJECTIVE: This
      article aims to address key issues in diagnosis and management to better equip
      general practitioners for their role in multidisciplinary management of patients
      with IBD. DISCUSSION: Making the diagnosis can be difficult, but is facilitated
      by appropriate clinical suspicion and sensible judgment as to who undergoes
      diagnostic tests such as colonoscopy. Treatment of ulcerative colitis has changed
      little in recent years, except for our improved ability to deliver mesalazine to
      the large bowel via the recent availability of several oral and rectal
      preparations. Prevention of relapse using these is an important strategy in the
      majority of patients. Treatment of Crohn disease is changing due to more
      realistic concepts of the natural history of the disease and the development of
      new, powerful anti-inflammatory therapies. Attention to issues other than
      intestinal inflammation such as nutrition, education and counselling, remain
      important in achieving optimal management.

PMID- 15861743
TI  - Coeliac disease.
AB  - BACKGROUND: Coeliac disease (CD) probably affects one in 100 Australians, but is
      greatly underdiagnosed. Heightened media interest in the negative effects of
      dietary gluten has led many patients to request testing for CD or follow
      inappropriate diets. Doctors have had little education in CD because of its
      perceived rarity. OBJECTIVE: This article summarises current knowledge of
      clinical presentations, optimal screening and diagnostic tests, and how the
      general practitioner can best assist patients in adopting a successful gluten
      free diet. DISCUSSION: Coeliac disease is associated with a range of conditions
      including type 1 diabetes, thyroid disease, osteoporosis, and iron deficiency
      with or without anaemia. Gastrointestinal symptoms may not be present. The GP
      therefore has an important role in considering CD in the differential diagnosis
      in a variety of clinical presentations. Antitransglutaminase IgA and total serum
      IgA are the preferred screening tests but may miss occasional patients with CD.
      Endoscopic duodenal biopsy while eating gluten is needed for definitive
      diagnosis. A gluten free diet is complex, and may fail without the involvement of
      a skilled dietician.

PMID- 15861744
TI  - Traveller's diarrhoea.
AB  - BACKGROUND: There has been little if any change in the incidence of traveller's
      diarrhoea over the past 20 years. OBJECTIVE: This article aims to provide a basic
      understanding on why travellers are more likely to experience diarrhoea during
      travel. DISCUSSION: In a 20 minute pretravel consultation time is precious, and
      providing information on traveller's diarrhoea often has a low priority over
      prescribing the necessary vaccinations and discussing antimalarials. Travellers
      do not follow the rules of eating and drinking safely, and diarrhoea is common.
      'What to do in the event of illness' is an important consideration. Presumptive
      treatment should be offered to all travellers whose itinerary and activities put
      them at risk.

PMID- 15861745
TI  - Giving evidence.
AB  - BACKGROUND: The Australian civil and criminal court systems are adversarial. They
      are based on the concept of two opposing sides, one eventually becoming the
      'winner' as determined by a neutral/independent judge. Doctors are often
      requested to present evidence on behalf of one of the 'sides', although it is
      imperative that their evidence remains unbiased or bipartisan. For most doctors,
      attending court is infrequent, perhaps contributing to the fear associated with
      being summonsed. OBJECTIVE: This article provides information and skills training
      for doctors on how to be 'expert witnesses' and giving evidence in court.
      DISCUSSION: With a good understanding of the issues involved and the provision of
      evidence, attending court may be made easier for doctors. Prior knowledge of the
      system and adequate preparation of the case is important in ensuring the medical
      evidence is both admissible and weighted correctly.

PMID- 15861746
TI  - Management of benign breast conditions. Part 2--breast lumps and lesions.
AB  - This is the second article in a series on breast disorders with an emphasis on
      diagnosis and management in the general practice setting. This article provides
      an overview of the investigation of patients with a breast symptom and discusses
      the assessment and management of benign breast lesions including localised
      nodularity, fibroadenomas and breast cysts.

PMID- 15861747
TI  - Patient education. What is a breast cyst?

PMID- 15861748
TI  - Managing mental illness in patients from CALD backgrounds.
AB  - BACKGROUND: Australian general practitioners are often the first point of call
      for people seeking mental health care including those from culturally and
      linguistically diverse (CALD) backgrounds, some of whom may be more at risk of
      having a mental illness but are failing to access the appropriate mental health
      care. OBJECTIVE: This article is intended to assist GPs in the recognition,
      diagnosis and management of mental illness in patients from CALD backgrounds by
      providing current research evidence and presenting some practical
      recommendations. More attention is paid to the larger CALD populations such as
      the southern European and Asian communities, and does not deal with indigenous
      Australians. DISCUSSION: There is an increasing call for GPs to have a key role
      in the detection, diagnosis and management of mental illness, including for
      patients from CALD backgrounds. Effective care requires that GPs are aware of,
      and understand how culture may influence recognition, diagnosis and management of
      mental illness in this group of patients.

PMID- 15861749
TI  - Can we prevent prostate cancer?
AB  - BACKGROUND: Prostate cancer is the second leading cause of cancer deaths among
      men. It is common in Australia, New Zealand, North America and North West Europe,
      but rare in Asia, Africa and South America. OBJECTIVE: This article reviews the
      role of chemopreventive agents for prostate cancer. The available evidence
      strongly suggests that dietary changes and supplementation with a variety of
      micronutrients, vitamins and trace elements may reduce the incidence and
      mortality of prostate cancer. DISCUSSION: Epidemiologic observations reveal lower
      cancer rates in those with diets rich in fruits, vegetables, vitamins, and a
      number of specific foods. This available data is adequate to clinically apply the
      role of various factors to possibly reduce the incidence of prostate cancer.

PMID- 15861750
TI  - Traumatic brain injury--the need for support and follow up.
AB  - BACKGROUND: Mild traumatic brain injury (MTBI) is the commonest type of brain
      injury. It is sometimes difficult to select patients who require ongoing follow
      up to avoid the sequelae of MTBI. OBJECTIVE: This article outlines the diagnosis
      and management of MTBI using case vignettes. DISCUSSION: General practitioners
      should be aware of the possible long term sequelae that may be the result of
      external factors, and provide support, follow up and eduction to patients with a
      history of MTBI.The management of postconcussive syndrome and MTBI are also
      discussed.

PMID- 15861751
TI  - A peer support program for international medical graduates.
AB  - International medical graduates (IMGs) form a significant part of the Australian
      general practice workforce. Many experience social and professional problems and
      perform poorly inThe Royal Australian College of General Practitioners Fellowship
      Examination. This article reports on a pilot program in Mackay, north Queensland
      that addressed some of these issues.

PMID- 15861752
TI  - Coeliac disease: a patient perspective.

PMID- 15861753
TI  - An unusual case of diarrhoea.
AB  - Case histories are based on actual medical negligence claims, however certain
      facts have been omitted or changed by the author to ensure the anonymity of the
      parties involved. Medication errors in general practice are relatively common.
      This article describes a medication error that led to a patient complaint and
      claim.

PMID- 15861754
TI  - Introduction of electronic prescribing in an aged care facility.
AB  - Residents of aged care facilities are at high risk of adverse drug events.
      Electronic prescribing may reduce some of these risks. This article reports on
      the introduction of electronic prescribing software to a residential aged care
      facility with the aim of improved medication safety.

PMID- 15861755
TI  - Peer support for cancer patients.
AB  - People directly affected by cancer report significant psychological distress.
      Peer support programs are based on the premise that shared experience is a
      valuable resource that assists individuals to adjust to, and cope effectively
      with, stressful events. This article considers two types of peer support service
      available to cancer patients--telephone peer support (the 'Cancer Connect'
      program) and cancer support groups.

PMID- 15861756
TI  - Killing George with kindness--is there such a thing as too much palliative care?
AB  - Early referral and anticipatory planning are central tenets of good palliative
      care. Each case, however, needs to be considered on its merits. Too many supports
      put in place at the wrong time may have adverse consequences for some patients. A
      clear understanding of the patient's understanding of their illness and
      prognosis, and appreciation of their mental state at each stage, are important in
      determining how much palliative care is enough.

PMID- 15861757
TI  - Are we more than the sum of our parts? Should we listen to Albert Einstein?

PMID- 15861758
TI  - Self assessed learning needs of rurally based IMGs.

PMID- 15861759
TI  - An evidence based clinical aid for cardiovascular disease--what do GPs think?

PMID- 15861760
TI  - Patient perceptions of the GP role in cancer management.
AB  - BACKGROUND: During the course of their cancer treatment, patients have to deal
      with a number of health professionals. We investigated patients' perceptions of
      the role of the general practitioner, with particular reference to GPs' ability
      to manage patients' cancer outside of the hospital setting. METHOD: We took a
      phenomenological approach, focussing on empowerment, and any central role of the
      GP. In depth interviews were conducted on the same haematological cancer patients
      over a 2 year period. Results were analysed for main themes regarding support and
      management of illness. RESULTS: Many patients had a long term relationship with
      an individual GP. They perceived GPs as providing a primarily supportive rather
      than treatment role outside of the hospital setting, and relied on them for
      clarification and reassurance. DISCUSSION: The personal, confiding relationship
      between the GP and cancer patient might be better exploited by specialists.
      Patients could feel more empowered in relation to their condition if provided
      with information by their GP that is more relevant and explicit. For this to
      occur, specialists must first provide GPs with timely and pertinent information
      about their cancer management.

PMID- 15861761
TI  - Low prostate specific antigen levels and normal digital rectal examination--a
      report on a follow up cohort in general practice.

PMID- 15861762
TI  - Water as a fast acting wax softening agent before ear syringing.
AB  - BACKGROUND: Dispute exists over the best treatment for softening occlusive
      earwax. Some require the patient to go away for days before returning for
      syringing. Some syringe immediately with no preparation. METHODS: An open,
      nonblinded, randomised controlled trial was conducted in one rural general
      practice. Effects of instillation of water into the ear canal for 15 minutes
      before syringing were compared to effects of syringing immediately. RESULTS:
      Thirty-nine ears (of 26 patients) were randomised. Ear wax was removed entirely
      by syringing in all ears. Prior instillation of water required a mean 7.5 (+/-
      7.3) attempts at syringing versus a mean 25.4 (+/- 39.4) attempts for ears that
      were syringed immediately (p=0.043). DISCUSSION: Prior installation of water
      before syringing seems to be an effective and simple method of reducing the
      number of attempts required to clear the ear of occlusive wax.

PMID- 15861764
TI  - New conditions for coverage will impose a host of new requirements on dialysis
      clinics.

PMID- 15861765
TI  - Finding a professional advisor for your practice.

PMID- 15861766
TI  - Is government investing enough in the nursing crisis? Federal support for nursing
      shortage remedies needs a boost.

PMID- 15861767
TI  - Who has rights, anyway? An ethical approach to dealing with difficult patients
      and staff.

PMID- 15861768
TI  - Vascular access.

PMID- 15861769
TI  - Nursing workforce issues: an ANNA perspective.

PMID- 15861770
TI  - Relationship between ambient air pollution and daily mortality of SARS in
      Beijing.
AB  - OBJECTIVE: To study the relationship between ambient air pollution and daily
      mortality of SARS in Beijing. METHODS: The approach of time-series Poisson
      regression was used to assess the relationship between daily SARS mortality,
      ambient air pollution, and other factors from April 25 to May 31, 2003 in
      Beijing. RESULTS: An increase of each 10 microg/m3 over a 5-day moving average of
      PM10, SO2 and NO2 corresponded to 1.06 (1.00-1.12), 0.74 (0.48-1.13) and 1.22
      (1.01-1.48) relative risks (RRs) of daily SARS mortality, respectively. The
      relative risks (RRs) values depended largely on the selection of lag days.
      CONCLUSION: The daily mortality of SARS might be associated with certain air
      pollutants in Beijing.

PMID- 15861771
TI  - Effect of salinity variations on the performance of activated sludge system.
AB  - OBJECTIVE: To investigate the influence of salinity variations on the performance
      of activated sludge systems, treating domestic wastewater. METHODS: The
      completely mixed reactor was used and operated in a batch-wise mode. The
      activated sludge taken from the Gaobeidian Wastewater Treatment Plant was used as
      a seeding sludge. Total organic carbon (TOC), oxygen uptake rate (OUR) and
      suspended solids (SS) were used as parameters to characterize the performance of
      the treatment systems. TOC was measured using a TOC-analyzer (TOC-5000, Japan).
      The OUR value was measured with a dissolved oxygen meter (YSI model-58). SS was
      measured gravimetrically. RESULTS: The TOC removal efficiency and the OUR value
      of activated sludge were not deteriorated when the NaCl shock concentration was
      less than 0.5 g/L. However, when the NaCl shock concentrations were up to 10g/L
      and 20 g/L, the OUR of activated sludge was reduced by 35% and TOC removal
      efficiency was dropped by 30%, compared with the control experiment without NaCl
      shock loading. CONCLUSION: The effect of NaCl shock loading on the activated
      sludge wastewater treatment system is dependant upon the NaCl concentrations and
      the degree of influence can be inferred through the change of substrate
      utilization rate at different shock NaCl loadings.

PMID- 15861772
TI  - Serial analysis of gene expression in Monascus aurantiacus producing citrinin.
AB  - OBJECTIVE: To construct a tag expression library of Monascus aurantiacus that
      could produce citrinin maximally on the thirteenth (0.966 mg/mL) day in the
      submerged culture. METHODS: Total RNA was extracted from the mycelium, cDNA was
      synthesized using the SuperScript choice system, and then, a SAGE library was
      successfully constructed according to the MicroSAGE method. RESULTS: Five hundred
      and ninety eight clones were obtained in SAGE library, and 120 clones were picked
      out randomly for identification and sequencing purpose. Eighty nine clones had
      positive inserts, 26 clones had no inserts and the remaining 5 clones had no site
      of NlaIII enzyme in inserts. There were seven repeated clones. CONCLUSION: With
      the aid of SAGE2000 software, 901 tags were obtained from 89 clones, representing
      686 unique transcripts. Six unique tags of them belong to highly expressed genes
      (Number of tags > or = 10) and 143 unique tags to moderately expressed genes
      (repeat tags > or = 2).

PMID- 15861773
TI  - Lead accumulation in surface soils and components of Balenites aegyptica specie
      in a Katsina urban area, Nigeria.
AB  - OBJECTIVE: The main objective of this paper is to assess the impact of various
      vehicular traffic densities on lead (Pb) accumulations in some environmental
      components in Katsina, a semi-arid urban area of Nigeria. METHODS: This was
      achieved by collecting and analyzing samples of surface soils, fruits, kernels,
      leaves, and barks of Balanites aegyptica from locations of different vehicular
      traffic densities in the area, and analyzing them for lead, using atomic
      absorption spectrophotometry. RESULTS: The results obtained revealed that the Pb
      concentration in the high, medium, low, and zero traffic density areas are, 75,
      53, 35, and 12 microg x g(-1) respectively for the fruit pulp. They are also16,
      13, 8, and 6 microg x g(-1) for fruit kernel and 44, 28, 17, and 9 microg x g(-1)
      respectively for leaves. For tree barks, the values are 138, 97, 64, and 18
      microg x g(-1) respectively while for under-tree-canopy soil samples the mean
      values are 99, 74, 44, and 17 microg x g(-1). In the case of outside-canopy soil
      samples, the mean values are 113, 91, 50, and 18 microg x g(-1) respectively for
      the various classes of vehicular traffic density. CONCLUSION: These results
      indicate a strong influence of vehicular traffic density on Pb emission into
      surrounding atmosphere and its subsequent precipitation on soil and components of
      B. aegyptica specie in the area. Of all the samples, tree bark should be the best
      index of assessing Pb pollution in the area, as it maintains the closest contact
      with the surrounding atmosphere. Since Pb has no known lower limit for human
      tolerance, there is an urgent need for Pb pollution control in the area to be
      effectively enforced.

PMID- 15861774
TI  - Environmental efficiency analysis of China's vegetable production.
AB  - OBJECTIVE: To analyze and estimate the environmental efficiency of China's
      vegetable production. METHODS: The stochastic translog frontier model was used to
      estimate the technical efficiency of vegetable production. Based on the estimated
      frontier and technical inefficiency levels, we used the method developed by
      Reinhard, et al. to estimate the environmental efficiency. Pesticide and chemical
      fertilizer inputs were treated as environmentally detrimental inputs. RESULTS:
      From estimated results, the mean environmental efficiency for pesticide input was
      69.7%, indicating a great potential for reducing pesticide use in China's
      vegetable production. In addition, substitution and output elasticities for
      vegetable farms were estimated to provide farmers with helpful information on how
      to reallocate input resources and improve efficiency. CONCLUSION: There exists a
      great potential for reducing pesticide use in China's vegetable production.

PMID- 15861775
TI  - Searching for a schizophrenia susceptibility gene in the 22q11 region.
AB  - OBJECTIVE: To investigate a genetic association for schizophrenia within
      chromosome 22q11 in a Chinese Han population. METHODS: The PCR-based restriction
      fragment length polymorphism (PCR-RFLP) analysis was used to detect three single
      nucleotide polymorphisms (SNPs), rs165655 (A/G base change) and rs165815 (C/T
      base change) present in the ARVCF (armadillo repeat gene deletion in
      velocardiofacial syndrome) locus, and rs756656 (A/C base change) in the LOC128979
      (expressed sequence tags, EST) locus, among 100 Chinese family trios consisting
      of fathers, mothers and affected offspring with schizophrenia. Genotype data were
      analyzed by using linkage disequilibrium (LD) methods including haplotype
      relative risk (HRR) analysis, transmission disequilibrium test (TDT) and
      haplotype transmission analysis. RESULTS: The genotype frequency distributions of
      three SNPs were all in Hardy-Weinberg equilibrium (P>0.05). Both the HRR and the
      TDT analysis showed that rs165815 was associated with schizophrenia (chi2=6.447,
      df=1, P=0.011 and chi2=6.313, df=1, P=0.012, respectively), whereas the other two
      SNPs did not show any allelic association. The haplotype transmission analysis
      showed a biased transmission for the rs165655-rs165815 haplotype system
      (chi2=17.224, df=3, P=0.0006) and for the rs756656-rs165655-rs165815 hapoltype
      system (chi2=20.965, df=7, P=0.0038). CONCLUSION: Either the ARVCF gene itself or
      a nearby locus may confer susceptibility to schizophrenia in a Chinese Han
      population.

PMID- 15861776
TI  - Differentiation of mesenchymal stem cells into dopaminergic neuron-like cells in
      vitro.
AB  - OBJECTIVE: To explore the way to induce mesenchymal stem cells (MSCs) to
      differentiate into dopaminergic neurons in vitro. METHODS: MSCs were obtained
      from rat bone marrow, cultured and passaged. MSCs used in this experiment had
      multipotency, which was indirectly proved by being induced to differentiate into
      chondrocytes and adipocytes. MSCs were cultured in medium containing 0.5 mmol/L
      IBMX for 2 days. Then the medium was replaced with induction medium, which
      contained GDNF, IL-1beta, mesencephalic glial-cell-conditioned medium and flash
      frozen mesencephalic membrane fragments. The surface markers of the
      differentiated neurons, such as NSE, nestin, MAP-2a, b and TH were detected by
      immunocytochemistry and Western blot after MSCs were cultured in induction medium
      for 7 days and 15 days. RESULTS: MSCs differentiated into neural progenitors and
      expressed nestin after MSCs were incubated with medium containing IBMX for 2 d.
      After the medium was replaced with induction medium containing many inducing
      agents, MSCs differentiated into neuron-like cells and dopaminergic neuron-like
      cells and expressed NSE, MAP-2a, b and TH. The percentage of NSE-positive cells,
      MAP-2a, b-positive cells and TH-positive cells was 30.032 +/- 2.489%, 41.580 +/-
      5.101% and 34.958 +/- 5.534%, respectively after MSCs were induced in medium
      containing GDNF, IL-1beta, mesencephalic glial-cell-conditioned medium and flash
      frozen mesencephalic membrane fragments for 15 days. CONCLUSION: MSCs can
      differentiate into dopaminergic neuron-like cells and are a new cell source for
      the treatment of neurodegeneration diseases and have a great potential for wide
      application.

PMID- 15861777
TI  - 8-hydroxydeoxyguanosine as a biomarker of oxidative DNA damage induced by
      environmental tobacco side-stream smoke and its mechanism.
AB  - OBJECTIVE: To study the genotoxicity effect of environmental tobacco side-stream
      smokes (ETSS) on oxidative DNA damage and its molecular mechanism. METHODS: DNA
      adduct 8-hydroxydeoxyguanosine (8-OHdG) was used as a biomarker of oxidative DNA
      damage. The level of 8-OHdG in DNA exposed to ETSS was detected by high
      performance liquid chromatography with electrochemical detection. Organic and
      inorganic components in ETSS were analyzed by gas chromatography-mass spectrum
      and atomic absorption spectrum respectively. RESULTS: Particle matters (PMs) and
      volatile organic compounds (VOCs) in ETSS could directly induce oxidative DNA
      damage and formation of 8-OHdG. There were 123 and 84 kinds of organic components
      in PMs and VOCs respectively, and 7 kinds of inorganic components in ETSS. Some
      components, especially quinones and polyphenols in ETSS, could produce free
      radicals in vitro by auto-oxidation without any biological activity systems, and
      with the catalytic reaction of metals, the DNA adduct 8-OHdG was produced.
      CONCLUSION: ETSS have biological oxidative effect on DNA in vitro and in vivo,
      and expressed direct genotoxicity. 8-OHdG is a valuable biomarker of oxidative
      DNA damage.

PMID- 15861778
TI  - A quantitative DNA methylation assay using mismatch hybridization and
      chemiluminescence.
AB  - OBJECTIVE: To develop a quantitative method for methylation analysis of the p16
      gene based on mismatch hybridization and chemiluminescence. METHODS: Genomic DNA
      was modified by sodium bisulfite to convert all unmethylated but not methylated
      cytosines to uracil, and subsequently a pair of primer having no CpG sites was
      designed for amplification target DNA containing methylated or unmethylated CpG
      sites. The PCR product spanning CpG sites were hybridized with two
      oligonucleotide probes which perfectly matched the methylated and unmethylated
      CpG sequences respectively, and the hybrids were detected by chemiluminescent
      method. The percentage of methylated target sequences could be estimated by
      calculating the ratio of signals obtained with two probes. RESULTS: The
      percentage of methylation of artificial mixtures DNA showed a linear relation.
      There was a negative correlation between the methyaltion index with p16
      transcriptional mRNA of p16 gene in tumor cell lines. CONCLUSION: Compared with
      existing methods, this assay is nonisotopic, rapid, simple, and can be widely
      applied to the study of DNA methylation.

PMID- 15861779
TI  - Quantitative structure-activity relationships for the toxicity of substituted
      benzenes to Cyprinus carpio.
AB  - OBJECTIVE: To measure the 96h-LC50 values of 32 substituted benzenes to the carp
      and to study the relationship between quantitative structure-activity and
      structural parameters of chemicals. METHODS: The acute toxicity values of 32
      substituted benzenes to the carp were determined in a semistatic test. The energy
      of the lowest unoccupied molecular orbital, and the highest occupied molecular
      orbital, the dipole moment and the molecular weight of substituted benzenes were
      calculated by the quantum chemical method MOPAC6.0. RESULTS: The range of the
      toxicity of studied compounds was broad, and the most toxic compound was
      pentachlorophenol, while the least toxic compound was 4-methylaniline. By the
      stepwise regression analyses, a series of Quantitative structure-activity
      relationships (QSAR) equations were derived from all compounds and subclasses.
      The equation log1/LC5o=0.759logP + 2.222 (R2 (adj)=0.818) was found to fit well
      and the average predicted percentage error was 6.16%. CONCLUSION: The toxicity of
      anilines and phenols to the carp could be modeled well by logP alone, whereas the
      toxicity of the halogenated benzenes and nitrobenznes not containing hydroxyl or
      amino group can be controlled by hydrophobic and electronic factors.

PMID- 15861780
TI  - Relationship between polymorphism of methylenetetrahydrofolate dehydrogenase and
      congenital heart defect.
AB  - OBJECTIVE: To investigate the relationship between G1958A gene polymorphism of
      methylenetetrahydrofolate dehydrogenase (MTHFD) and occurrence of congenital
      heart disease (CHD) in North China. METHODS: One hundred and ninety-two CHD
      patients and their parents were included in this study as case group in Liaoning
      Province by birth defect registration cards, and 124 healthy subjects (age and
      gender matched) and their parents were simultaneously selected from the same
      geographic area as control. Their gene polymorphism of MTHFD G1958A locus was
      examined with PCR-RFLP, and serum folic acid and homocysteine (Hcy) levels were
      tested with radio-immunoassay and fluorescence polarization immunoassay (FPIA).
      RESULTS: There existed gene polymorphism at MTHFD G1958A locus in healthy
      subjects living in North China. The percentages of GG, GA, and AA genotype were
      57.98%, 35.57%, and 6.45% respectively, and the A allele frequency was 24.23%,
      which was significantly different from Western population. No difference was
      observed when comparing genotype distribution and allele frequency between the
      case and control groups, so was the result from the comparison between genders.
      The A allele frequency of arterial septal defect patients' mothers (10.87%) was
      significantly lower than that of controls (28.15%) (P=0.014), with OR=0.31 (95%
      CI: 0.09-0.84), and no difference in the other subgroups. The percentage of at
      least one parent carrying A allele in arterial septal defect subgroup (43.48%)
      was significantly lower than that in controls (69.64%) (P=0.017), with OR=0.34
      (95% CI: 0.12-0.92). The analysis of genetic transmission indicated that there
      was no transmission disequillibrium in CHD nuclear families. Their serum folic
      acid level was significantly higher than that of controls (P=0.000), and Hcy
      level of the former was higher than that of the latter with no statistical
      significance (P>0.05). Serum Hcy and folic acid levels of mothers with gene
      mutation were lower than those of mothers with no mutation. CONCLUSION: No
      significant difference of genotype distribution and allele frequency existed
      between CHD patients and healthy population. MTHFD G1958A mutation in parents
      (particularly in mother) can decrease the risk of arterial septal defect in
      offspring. The possible mechanism of protection might be mutation, which can
      increase MTHFD enzyme activity, folic acid metabolism and homocysteine
      remethylation, and decrease Hcy level.

PMID- 15861781
TI  - Mechanisms of apigenin-7-glucoside as a hepatoprotective agent.
AB  - OBJECTIVE: Ixeris chinesis (Thunb.) Ankai has been used as a Chinese folk
      medicine, but only scanty information is available on the physiological and
      biochemical functions of the compounds extracted from I. chinesis. In the present
      study the effects of apigenin-7-glucoside (APIG) isolated from I. chinesis
      against liver injury caused by carbon tetrachloride (CCl4) were investigated.
      METHODS: The contents of malondialdehyde (MDA), glutamic pyruvic transaminase
      (GPT), glutamic oxaloacetic transaminase (GOT), and reduced glutathione (GSH)
      were evaluated by spectrophotography. The content of 8-Hydroxydeoxyguanosine (8
      OHdG) was measured with high-performance liquid chromatography (HPLC) equipped
      with electrochemical and UV detection methods. The antioxidant activity of APIG
      was evaluated using chemiluminescence single photon counting technology. RESULTS:
      CCl4 significantly increased the enzyme activities of GPT and GOT in blood serum,
      as well as the level of MDA and 8-OHdG in liver tissue, and decreased the levels
      of GSH. Pretreatment with APIG was able not only to suppress the elevation of
      GPT, GOT, MDA and 8-OHdG, and inhibit the reduction of GSH in a dose-dependent
      manner in vivo, but also to reduce the damage of hepatocytes in vitro. On the
      other hand, we also found that APIG had strong antioxidant activity against
      reactive oxygen species (ROS) in vitro in a concentration-dependent manner.
      CONCLUSION: The hepatoprotective activity of APIG is possibly due to its
      antioxidant properties, acting as scavengers of ROS. These results obtained in
      vivo and in vitro suggest that APIG has protective effects against hepatic
      oxidative injury induced by chemicals. Further studies on the pharmaceutical
      functions and immunological responses of APIG may help its clinical application.

PMID- 15861782
TI  - Influence of the pressure on the properties of chromatographic columns. I.
      Measurement of the compressibility of methanol-water mixtures on a mesoporous
      silica adsorbent.
AB  - The compressibilities of aqueous solutions of methanol or acetonitrile containing
      0, 20, 40, 60, 80 and 100% (v/v) organic solvent were measured with a dynamic
      chromatographic method. The elution volumes of thiourea samples (2 microL) in
      these solutions were measured at different average column pressures, adjusted by
      placing suitable capillary restrictors on-line, after the detector. The
      reproducibility of the measurements was better than 0.2%. In the range of average
      pressures studied (10-350 bar), the maximum change in elution volume of thiourea
      is 1.3% (in pure water) and 4.0% (in pure methanol). This difference is due to
      the different compressibilities of these pure solvents. For mixtures, the plots
      of the elution volume of thiourea versus the pressure are convex downward, which
      is inconsistent with the opposite curvature predicted by the classical Tait model
      of liquid compressibility. This difference is explained by the variation of the
      amount of thiourea adsorbed with the pressure. The deconvolution of the two
      effects, adsorption of thiourea and solvent compressibility, allows a fair and
      consistent determination of the compressibilities of the methanol-water mixtures.
      A column packed with non-porous silica particles was also used to determine the
      compressibility of methanol-water and acetonitrile-water mixtures. A negative
      deviation by respect to ideal behavior was observed.

PMID- 15861783
TI  - Influence of pressure on the properties of chromatographic columns. II. The
      column hold-up volume.
AB  - The effect of the local pressure and of the average column pressure on the hold
      up column volume was investigated between 1 and 400 bar, from a theoretical and
      an experimental point of view. Calculations based upon the elasticity of the
      solids involved (column wall and packing material) and the compressibility of the
      liquid phase show that the increase of the column hold-up volume with increasing
      pressure that is observed is correlated with (in order of decreasing importance):
      (1) the compressibility of the mobile phase (+1 to 5%); (2) in RPLC, the
      compressibility of the C18-bonded layer on the surface of the silica (+0.5 to
      1%); and (3) the expansion of the column tube (<0.001%). These predictions agree
      well with the results of experimental measurements that were performed on columns
      packed with the pure Resolve silica (0% carbon), the derivatized Resolve-C18 (10%
      carbon) and the Symmetry-C18 (20% carbon) adsorbents, using water, methanol, or n
      pentane as the mobile phase. These solvents have different compressibilities.
      However, 1% of the relative increase of the column hold-up volume that was
      observed when the pressure was raised is not accounted for by the
      compressibilities of either the solvent or the C18-bonded phase. It is due to the
      influence of the pressure on the retention behavior of thiourea, the compound
      used as tracer to measure the hold-up volume.

PMID- 15861784
TI  - Oligonucleotide trapping method for transcription factor purification systematic
      optimization using electrophoretic mobility shift assay.
AB  - Oligonucleotide trapping, where a transcription factor-DNA response element
      complex is formed in solution and then recovered (trapped) on a column, was
      optimized for the purification of CAAT/enhancer binding protein (C/EBP) from rat
      liver nuclear extract. Electrophoretic mobility shift assays (EMSAs) with
      ACEP24(GT)5 oligonucleotide, containing the CAAT element, was used to estimate
      thebinding affinity and concentration of C/EBP in the nuclear extract and then
      low concentrations of protein and oligonucleotide, which favor specific binding,
      were used for all further experiments. Also using EMSA, the highest
      concentrations of competitors, which inhibit non-specific binding but do not
      inhibit oligonucleotide binding by C/EBP, were determined to be 932 nM T18
      (single-stranded DNA), 50 ng/ml heparin (non-DNA competitor), and 50 microg/ml
      poly(dI:dC) (duplex DNA). Inclusion of 0.1% Tween-20 improved DNA binding. For
      complex formation, 110 microg nuclear extract was diluted to 0.2 nM C/EBP
      (apparent Kd of C/EBP) and 1.34 nM ACEP24(GT)5 was added, along with Tween-20 and
      the competitors. After incubation, the complex was trapped by annealing the (GT)5
      tail of the C/EBP-[ACEP24(GT)5] complex to an (AC)5-Sepharose column under flow
      at 4 degrees C. The column was washed with 0.4 M NaCl and the protein eluted with
      1.2 M NaCl. The purification typically resulted in two proteins of apparent
      molecular mass 32000 and 38000. The smaller one, the major product, was
      identified to be C/EBP-alpha. The yield was 2.1 microg (66 pmol) of purified
      C/EBP-alpha p32. This systematic approach to oligonucleotide trapping is
      generally applicable for the purification of other transcription factors.

PMID- 15861785
TI  - Fingerprint quality control of Tianjihuang by high-performance liquid
      chromatography-photodiode array detection.
AB  - A novel, simple and accurate fingerprint method was developed using high
      performance liquid chromatography-photodiode array detection (HPLC-DAD) for the
      quality control of Hypericum japonicum thunb (Tianjihuang), a Chinese herbal
      medicine used for the treatment of several bacterial diseases, infectious
      hepatitis, gastrointestinal disorder, internal hemorrhage and tumors. For the
      first time, the feasibility and advantages of employing chromatographic
      fingerprint were investigated and demonstrated for the evaluation of Tianjihuang
      by systematically comparing chromatograms with a professional analytical software
      recommended by State Food and Drug Administration (SFDA). Our results revealed
      that the chromatographic fingerprint combining similarity evaluation could
      efficiently identify and distinguish raw herbs of Tianjihuang from different
      sources. The effects resulted from collecting locations, harvesting time and
      storage time on herbal chromatographic fingerprints were also examined.

PMID- 15861786
TI  - Quality evaluation of Flos lonicerae through a simultaneous determination of
      seven saponins by HPLC with ELSD.
AB  - A new HPLC coupled with evaporative light scattering detection (ELSD) method has
      been developed for the simultaneous quantitative determination of seven major
      saponins, namely macranthoidin B (1), macranthoidin A (2), dipsacoside B (3),
      hederagenin-28-O-beta-D-glucopyranosyl(6-->1)-O-beta-D-glucopyranosyl ester (4),
      macranthoside B (5), macranthoside A (6), and hederagenin-3-O-alpha-L
      arabinopyranosyl(2-->1)-O-alpha-L-rhamnopyranoside (7) in Flos Lonicerae, a
      commonly used traditional Chinese medicine (TCM) herb. Simultaneous separation of
      these seven saponins was achieved on a C18 analytical column. The mobile phase
      consisted of (A) acetonitrile-acetic acid (95:0.5) and (B) 0.5% aqueous acetic
      acid using a gradient elution of 29%A at 0-10 min, 29-46%A at 10-25 min and 46%A
      at 25-30 min. The drift tube temperature of ELSD was set at 106 degrees C, and
      with the nitrogen flow-rate of 2.6 l/min. All calibration curves showed good
      linear regression (r2>0.9922) within test ranges. This method showed good
      reproducibility for the quantification of these seven saponins in Flos Lonicerae
      with intra- and inter-day variations of less than 3.0% and 6.0%, respectively.
      The validated method was successfully applied to quantify seven saponins in five
      sources of Flos Lonicerae, which provides a new basis of overall assessment on
      quality of Flos Lonicerae.

PMID- 15861787
TI  - Separation of water-soluble vitamins by reversed-phase high performance liquid
      chromatography with ultra-violet detection: application to polyvitaminated
      premixes.
AB  - Nine water-soluble vitamins: [thiamine (B1), ascorbic acid (C), nicotinamide
      (PP), pyridoxine (B6), calcium pantothenate (B5), folic acid (B9), cyanocobalamin
      (B12), riboflavin (B2) and biotin (B8)] were separated on a YMC-Pack Pro C18
      column (250 mm x 4.6 mm, 5 microm particle size) in a single run with a gradient
      elution of mobile phase consisting of 0.025% trifluoroacetic acid pH 2.6 (solvent
      A) and acetonitrile (solvent B). The separation was achieved within 17 min with a
      flow rate of 0.8 ml min(-1) and the detection was performed at two wavelengths
      (210 and 275 nm). The calibration graphs plotted with six concentrations of each
      vitamin were linear with a regression coefficient R2 > 0.995. The method was
      applied for the quantification of vitamins B1, C, PP, B6, B5, B9 B2 and B8 in
      polyvitaminated premixes (premixes) used for the fortification of infant
      nutrition products. The sample preparation involves an aqueous extraction of
      vitamins and two different samples dilution were used prior the LC-analysis. The
      specificity of the method was demonstrated by the retention characteristics, UV
      spectra and by comparing the peak purity with the standard of each vitamin. The
      repeatability of the method was evaluated at different level of concentrations on
      12 premixes and the coefficients of variation (CVr) were below 6.5%. The values
      of the intermediate precision (CV1) were below 9.6% (n = 6). The concentrations
      of vitamins found in premixes with our method were comparable to the declared
      values, since no bias was found between the two sets of results at 95%
      confidence. The simplicity of the procedure should make it highly desirable for
      quality control of premixes in the food industry.

PMID- 15861788
TI  - Monitoring glycosylation pattern changes of glycoproteins using multi-lectin
      affinity chromatography.
AB  - Previously, we reported that the distribution of glycoproteins into the lectin
      displacement fractions of a multi-lectin affinity column was determined by the
      glycosylation patterns of the proteins. This distribution was observed by the
      sequential use of displacers specific to the lectins in the column. In this study
      we have evaluated the multi-lectin column (containing Concanavalin A, Wheat germ
      agglutinin and Jacalin lectin) to screen glycoproteins with known glycosylation
      pattern changes. The presence of a glycoprotein in a given displacer fraction was
      determined by LC-MS/MS analysis of a tryptic digest. We have used the enzyme
      neuraminidase to modify the oligosaccharide chains present in human transferrin,
      and used the enzymes, neuraminidase and fucosidase, to modify glycoproteins
      present in human serum. Then, by comparison with the untreated samples, we
      demonstrated a distribution shift of the enzyme-treated serum glycoproteins in
      the displacement fractions isolated from the multi-lectin column. The fractions
      were analyzed by a protein assay, Sequest rank comparison and peak area
      measurement from the extracted ion chromatogram. The results indicated that the
      multi-lectin affinity column (M-LAC) is sensitive to changes in the content of
      sialic acid and fucosyl residues present in serum glycoproteins, and has the
      potential to be used to screen serum proteins for glycosylation changes due to
      disease. In addition, the use of a glycosidase to induce specific structural
      changes in glycoproteins can support the development of multi-lectin column
      formats specific for detecting changes in the glycoproteome of certain diagnostic
      fluids and types of disease.

PMID- 15861789
TI  - Determination of triptolide in root extracts of Tripterygium wilfordii by solid
      phase extraction and reverse-phase high-performance liquid chromatography.
AB  - Extracts of Tripterygium wilfordii roots have a long history of use in
      traditional Chinese medicine and have shown great promise in recent clinical
      trials as a treatment for rheumatoid arthritis. The major active component of
      Tripterygium root extracts is the diterpenoid triptolide. This paper describes a
      method for the determination of triptolide in root extracts that is suitable for
      the analysis of many small samples simultaneously. Extracts are applied to
      aminopropyl solid-phase extraction (SPE) tubes that are then eluted with
      dichloromethane-methanol (49:1, v/v). The eluate is chromatographed on a
      pentafluorophenyl HPLC column using an acetonitrile:water gradient. Triptolide is
      quantified by ultraviolet detection at 219 nm. Using this method, it was shown
      that smaller diameter roots with secondary growth contained higher triptolide
      concentrations than larger roots. This suggests that roots to be used for
      production of the drug extract could be harvested while still small, which would
      reduce the growing time necessary and thus be economically beneficial for the
      growers.

PMID- 15861790
TI  - Zwitterionic ion chromatography with carboxybetaine surfactant-coated particle
      packed and monolithic type columns.
AB  - Both particle packed (25 cm x 0.46 cm I.D. SUPELCOSIL 5 microm C18) and
      monolithic type (10 cm x 0.46 cm I.D. Merck Chromolith Performance C18) reversed
      phase substrates were dynamically coated with a carboxybetaine type zwitterionic
      surfactant ((dodecyldimethyl-amino) acetic acid) and investigated as stationary
      phases for use in zwitterionic ion chromatography (ZIC). Investigations into
      eluent concentration and pH were carried out using KCl eluents containing 0.2 mM
      of the carboxybetaine surfactant to stabilise the column coatings. It was found
      that eluent concentration decreased anion retention whilst simultaneously
      increasing peak efficiencies, which may be due to the dissociation of intra- and
      inter-molecular salts of the carboxybetaine surfactant under higher ionic
      strength conditions. The Effect of eluent pH was an increase in anion retention
      with decreased eluent pH due to the increased protonation of the weak acid
      terminal group of the carboxybetaine, causing both a relative increase in the
      positive charge of the stationary phase and less repulsion of the anions by the
      dissociated weak acid group. The carboxybetaine-coated monolithic phase was
      applied to rapid anion separations using elevated flow rates and flow rate
      gradients.

PMID- 15861791
TI  - Comprehensive two-dimensional liquid chromatography and hyphenated liquid
      chromatography to study the degradation of poly(bisphenol A)carbonate.
AB  - Size exclusion chromatography (SEC), gradient polymer elution chromatography
      (GPEC) and liquid chromatography at critical conditions (LC-CC) have been
      developed and applied to observe chemical changes in poly(bisphenol A)carbonate
      (PC) due to hydrolytic degradation. Especially LC-CC appeared to be very
      successful to observe differences in functionality of PC as result of hydrolytic
      degradation. Observed differences due to degradation could be identified by
      (semi) on-line coupling to matrix assisted laser desorption-ionization time-of
      flight mass spectrometry (MALDI-TOF-MS). The differences in functionality could
      be attributed to the formation of different end-groups, i.e. OH end-groups. In
      addition, comprehensive two-dimensional liquid chromatography (2D-LC) has been
      applied successfully to study the hydrolytic degradation of PC. LC-CC x SEC
      showed that the formation of PC with different end-groups occurred over the whole
      molecular mass range. This information could not be obtained with the separate
      liquid chromatographic techniques, thereby illustrating the added value of 2D-LC.

PMID- 15861792
TI  - A better global resolution function and a novel iterative stochastic search
      method for optimization of high-performance liquid chromatographic separation.
AB  - HPLC optimization strategy consists of four elements; experimental design,
      retention modeling, quality criteria function, and optimum search method. In this
      paper we present a simple, superior alternative to general classes of classical
      resolution functions (S function) and a novel optimum search algorithm (iterative
      stochastic search, ISS) for HPLC optimization. Comparison of S with general
      classes of resolution-based quality criteria functions (Rs, Rp, and Rmin) shows
      superior features such as correct assessment of favorable separation conditions,
      preservation of peak pair contributions, elimination of arbitrary cut-off values,
      and a unique capability to interpret absolute significance of function values
      through a simple inequality. The proposed ISS algorithm is more robust than
      standard methods and it is easily applicable to hyperdimensional optimization.
      ISS also shows clear advantages in its ability to correctly identify the global
      optimum (instead of local optimum), with higher precision, with more efficient
      use of computation cycles, and with easier implementation. Successful application
      of S and ISS to HPLC optimization was demonstrated in the separation of
      representative functionalities (sugars, alcohols, and organic acids) present in
      microbial fermentations. Both the optimal and pathological (worst) conditions
      were successfully predicted and experimentally verified.

PMID- 15861793
TI  - Quantitative determination of the ligand content in Benzamidine Sepharose 4 Fast
      Flow media with ion-pair chromatography.
AB  - A quantitative hydrochloric acid hydrolysis-HPLC method was developed for the
      analysis of the ligand content of Benzamidine Sepharose 4 Fast Flow media. The
      method requires about 100 mg of dried sample and simple reaction vials can be
      utilised. Release of the ligand (p-aminobenzamidine) from the base matrix
      (Sepharose 4 Fast Flow) was obtained after hydrolysis for 180min at 70 degrees C
      in concentrated hydrochloric acid. When Benzamidine Sepharose 4 Fast Flow media
      were treated this way p-aminobenzoic acid and p-aminobenzamidine were the only
      products released from the ligand. A chromatographic system based on ion-pair
      reversed phase separation was used to quantify these ligand products. The mobile
      phase was made acidic enough to make p-aminobenzoic acid and p-aminobenzamidine
      positively charged in order to make ion-pair formation with hexanesulfonic acid
      possible. The relative standard deviation of th e method was below 2% and no
      systematic errors could be detected when the results were compared to an
      independent method based on elemental analysis (nitrogen). The new HPLC method
      was used to analyse ligand densities in the range of 2-20 micromol/ml medium.

PMID- 15861794
TI  - Effect of mobile phase composition on the SMB processes efficiency. Stochastic
      optimization of isocratic and gradient operation.
AB  - The solvent composition was adjusted in a theoretical study in order to maximize
      the efficiency of a simulated moving bed (SMB) process. The isocratic realization
      of the process as well as the solvent gradient mode were considered. The solvent
      composition and the flow rates were used as decision variables in a random search
      optimization algorithm known to be a reliable tool for nonlinear programming
      problems. The results of the optimization indicate that the optimal composition
      of the mobile phase depends strongly on the feed concentration. The asymmetry of
      the internal concentration profiles, which has a negative effect on the
      separation efficiency, can be partly damped by an increase of the solvent
      strength. In the cases studied the optimal solvent strength determined for
      concentrated feed streams is higher than that for diluted ones. Moreover, the
      optimum is strongly influenced by the value of the selectivity factor and its
      dependency on the mobile phase composition. Different results were obtained for
      cases, in which the separation factor increases with increasing the modifier
      concentration, than for cases, in which the separation factor decreases with
      increasing the modifier concentration. A similar analysis was performed for a
      solvent gradient SMB process, in which different solvents are used at the two
      inlet ports: a weak solvent in the feed stream and a strong solvent in the
      desorbent stream. Again the optimal mobile phase composition was strongly
      affected by the type of the isotherms and their non-linearity. The potential of a
      gradient SMB process in terms of increasing the productivity and reducing the
      eluent consumption is exemplified.

PMID- 15861795
TI  - Molecularly imprinted solid-phase extraction of (-)-ephedrine from Chinese
      Ephedra.
AB  - Method of molecularly imprinted solid phase extraction (MISPE) of (-)-ephedrine
      from Chinese Ephedra has been developed in the research. The molecularly
      imprinted polymer (MIP) with good selectivity and affinity for (-)-ephedrine was
      synthesized with (-)-ephedrine as the template, methacrylic acid as the
      functional monomer. The washing and elution conditions in MISPE were selected and
      optimized for efficient analyte extraction and sample clean-up. A clean
      analytical HPLC base line of ephedra extract was obtained after MISPE, which
      indicated that the sample pre-treatment was efficient. Good recovery and
      precision were obtained in the assessment for the MISPE-HPLC procedure, which
      demonstrated it is a reliable method and can be used for the determination of (-)
      ephedrine in herbal ephedra.

PMID- 15861796
TI  - Optimisation of poly-beta-hydroxyalkanoate analysis using gas chromatography for
      enhanced biological phosphorus removal systems.
AB  - Poly-beta-hydroxyalkanoate (PHA) is a polymer commonly used in carbon and energy
      storage for many different bacterial cells. Polyphosphate accumulating organisms
      (PAOs) and glycogen accumulating organisms (GAOs), store PHA anaerobically
      through metabolism of carbon substrates such as acetate and propionate. Although
      poly-beta-hydroxybutyrate (PHB) and poly-beta-hydroxyvalerate (PHV) are commonly
      quantified using a previously developed gas chromatography (GC) method, poly-beta
      hydroxy-2-methylvalerate (PH2MV) is seldom quantified despite the fact that it
      has been shown to be a key PHA fraction produced when PAOs or GAOs metabolise
      propionate. This paper presents two GC-based methods modified for extraction and
      quantification of PHB, PHV and PH2MV from enhanced biological phosphorus removal
      (EBPR) systems. For the extraction of PHB and PHV from acetate fed PAO and GAO
      cultures, a 3% sulfuric acid concentration and a 2-20 h digestion time is
      recommended, while a 10% sulfuric acid solution digested for 20h is recommended
      for PHV and PH2MV analysis from propionate fed EBPR systems.

PMID- 15861797
TI  - Direct quantitative analysis of phthalate esters as micro-contaminants in
      cleanroom air and wafer surfaces by auto-thermal desorption--gas chromatography-
      mass spectrometry.
AB  - This study established an analytical method for the trace analyses of two
      phthalate esters, including diethyl phthalate (DEP) and di-n-butyl phthalate
      (DBP), known as the major constituents of cleanroom micro-contamination
      detrimental to the reliability of semiconductor devices. Using thermal desorption
      coupled with a GC-MS system, standard tubes were prepared by delivering liquid
      standards pre-vaporized by a quasi-vaporizer into Tenax GR tubes for calibration.
      This method was capable of achieving detection limits of 0.05 microg m(-3) for
      0.1 m3 air samples and 0.03 ng cm(-2) for 150-mm wafer surface density. Actual
      samples collected from a semiconductor cleanroom showed that the concentration of
      DBP in a polypropylene wafer box (0.45 microg m(-3)) was nearly four times higher
      than that in the cleanroom environment (0.12 microg m(-3)). The surface
      contamination of DBP was 0.67 ng cm(-2) for a wafer stored in the wafer box for
      24 h. Furthermore, among the three types of heat-resistant O-ring materials
      tested, Kalrez was found to be particularly suitable for high-temperature
      processes in semiconductor cleanrooms due to their low emissions of organic
      vapors. This analytical procedure should serve as an effective monitoring method
      for the organic micro-contamination in cleanroom environments.

PMID- 15861798
TI  - Study of a core-shell type impact modifier by inverse gas chromatography.
AB  - Inverse gas chromatography (IGC) has been used to study the Lewis acid-base
      properties of a technologically and commercially important core-shell type
      elastomer (MBS rubber). The parameters determined were the dispersive component
      of the surface tension, the surface free energy, the enthalpy and the entropy of
      adsorption of polar and apolar probes, the surface Lewis acidity constant (Ka),
      and the surface Lewis basicity constant (Kb). The results show that the MBS
      rubber is amphoteric but strongly Lewis basic. It is weakly Lewis acidic. The
      results are in accord with the analysis of the molecular structure of PMMA, the
      shell component of this impact modifier (IM). The interactivity of this elastomer
      with the remaining materials in multicomponent polymeric systems is expected to
      be strongly influenced by the particular surface energetic properties of the MBS
      rubber. The results presented would contribute to the interpretation, forecast
      and optimization of the adhesion properties and phase preferences shown by this
      impact modifier when incorporated in such complex polymeric systems as polymer
      blends and composites.

PMID- 15861799
TI  - Development of a solid-phase extraction/gas chromatographic-mass spectrometric
      method for quantification of succinic acid in nucleoside derivatives for
      oligonucleotide synthesis.
AB  - A solid-phase extraction (SPE)/gas chromatographic-mass spectrometric (GC-MS)
      method was developed for analysing residual succinic acid in nucleoside
      derivatives to be used in oligonucleotide synthesis. Use of a SPE protocol,
      enabled most of the derivatives to be trapped, thereby creating eluates enriched
      in succinic acid. GC-MS was used to quantify the amount of residual succinic acid
      in four different nucleoside preparations, with succinate concentrations varying
      from 0.18 to 0.24% (w/w). The within-day repeatability of the method was found to
      be 1.25% RSD. A linear relationship was observed between the amount of succinic
      acid in the sample and the GC-MS peak area, with a correlation coefficient of
      0.9997 in the concentration interval 0.05-2.5% (w/w). Recoveries were measured by
      the addition of internal standards to working solutions and varied between 99.8
      and 102.6%.

PMID- 15861800
TI  - Chiral separation of amines in subcritical fluid chromatography using
      polysaccharide stationary phases and acidic additives.
AB  - The chiral separation of basic compounds by subcritical fluid chromatography
      (SFC) is often unsuccessful, due possibly to multiple interactions of the analyte
      with the mobile and stationary phase. Incorporation of a strong acid,
      ethanesulfonic acid (ESA), into the sample diluent and mobile phase modifier
      gives a dramatic improvement in these separations. Screening with ethanol
      containing 0.1% ESA on CHIRALPAK AD-H gave separation of 36 of 45 basic compounds
      previously not separated in SFC. The mechanism appears to involve the separation
      of an intact salt pair formed between the basic compound and ESA. Other
      modifiers, other acids and one additional stationary phase were examined and
      found to yield additional separations.

PMID- 15861801
TI  - Determination of herbicides in mineral and stagnant waters at ng/L levels using
      capillary electrophoresis and UV detection combined with solid-phase extraction
      and sample stacking.
AB  - In this work, the combined use of solid-phase extraction (SPE) and on-line
      preconcentration strategies as normal stacking mode (NSM) and stacking with
      matrix removal (SWMR) for the ultrasensitive and simultaneous capillary
      electrophoresis-ultraviolet analysis (CE-UV) of five triazolopyrimidine
      sulfonanilide pesticides (i.e., diclosulam, cloransulam-methyl, flumetsulam,
      metosulam and florasulam) in different types of water is investigated. An
      adequate separation electrolyte for the separation and stacking of these
      pesticides was obtained, considering also its compatibility with MS detection,
      which consisted of 24 mM formic acid and 16 mM ammonium carbonate at pH 6.4. It
      was observed that the use of this running buffer together with the SWMR
      preconcentration method provided the best results in terms of sensitivity
      (between 6.54 and 11.9 microg/L) and peak efficiency (up to 550000 theoretical
      plates per meter, NTP/m). When this on-line preconcentration procedure was
      combined with an off-line sample preconcentration step as SPE using C18
      cartridges, the selected herbicides could be detected in the ng/L range. The
      optimized SPE-SWMR-CE-UV method was applied to the determination of the selected
      group of pesticides in spiked and non-spiked mineral and stagnant waters.
      Recoveries ranged between 55 and 110% and limits of detection between 131 and 342
      ng/L. This work shows the great possibilities of the combined use of SPE-SWMR-CE
      UV to overcome the sensitivity problems usually linked to CE analysis.

PMID- 15861802
TI  - Approach to quasi stationary electrokinetic chromatography.
AB  - A partial filling (PF) electrokinetic chromatography (EKC) system in combination
      with the application of weak counter pressures was built up by the combination of
      an UV-active polymeric dye, Poly R-478, used as additive in the separation buffer
      (SB) zone and an UV-permeable borate background buffer (BB). The electroosmotic
      flows of the buffers were equalized by matching their ionic strengths to achieve
      best efficiency. The influence of the pressure for the injection of the
      separation buffer and the effect of the counter pressure on the breakthrough of
      the separation buffer zone was investigated. The quasi stationary state of the
      separation buffer zone was evaluated by recording breakthrough curves. Based on
      these data the counter pressure was manipulated so that the separation buffer
      zone became quasi stationary and a large interference-free migration time window
      results. The system was optimized using a mixture of amino/nitroaromatics as test
      compounds.

PMID- 15861803
TI  - Vesicles as pseudostationary phase for enantiomer separation by capillary
      electrophoresis.
AB  - A vesicle-forming single-tailed amino acid derivatized surfactant, sodium N-(4-n
      dodecyloxybenzoyl)-L-valinate (SDLV) has been used as a chiral selector in
      micellar electrokinetic chromatography to study the molecular recognition of
      sterically hindered atropisomeric compounds (+/-)binaphthol, (+/-)binaphthyl
      diamine, (+/-)binaphthol phosphate, Troger's base and the chiral compound benzoin
      (BZN). The aggregation behavior and microstructure of the surfactant were studied
      in separation buffer. The amphiphile was found to form bilayer vesicles in dilute
      aqueous solutions. The chromatographic separation of enantiomers by use of large
      liposome-like vesicles spontaneously formed by the amphiphile was explored. The
      separations were optimized with respect to voltage, pH, and surfactant and buffer
      concentrations. The resolutions obtained for the above mentioned racemates by use
      of SDLV vesicles as chiral selectors are higher compared to those reported for
      other chiral surfactant monomers. The results have been discussed in light of the
      aggregation behavior of the amphiphile in buffered aqueous solutions.

PMID- 15861804
TI  - Dual-purpose sample trap for on-line strong cation-exchange
      chromatography/reversed-phase liquid chromatography/tandem mass spectrometry for
      shotgun proteomics. Application to the human Jurkat T-cell proteome.
AB  - A dual-purpose sample-trapping column is introduced for the capacity enhancement
      of proteome analysis in on-line two-dimensional nanoflow liquid chromatography
      (strong cation-exchange chromatography followed by reversed-phase liquid
      chromatography) and tandem mass spectrometry. A home-made dual trap is prepared
      by sequentially packing C18 reversed-phase (RP) particles and SCX resin in a
      silica capillary tubing (1.5 cm x 200 microm I.D. for SCX, 0.7 cm x 200 microm
      for RP) ended with a home-made frit and is connected to a nanoflow column having
      a pulled tip treated with an end frit. Without having a separate fraction
      collection and concentration process, digested peptide mixtures were loaded
      directly in the SCX part of the dual trap, and the SCX separation of peptides was
      performed with a salt step elution initiated by injecting only 8 microL of
      NH4HCO3 solution from the autosampler to the dual trap. The fractionated peptides
      at each salt step were directly transferred to the RP trap packed right next to
      the SCX part for desalting, and a nanoflow LC-MS-MS run was followed. During the
      sample loading-SCX fractionation-desalting, flow direction was set to bypass the
      analytical column to prevent contamination. The entire 2D-LC separation and MS-MS
      analysis were automated. Evaluation of the technique was made with an injection
      of 15 microg peptide mixtures from human Jurkat T-cell proteome, and the total
      seven salt step cycles followed by each RPLC run resulted in an identification of
      681 proteins.

PMID- 15861805
TI  - Determination of adsorption isotherms of proteins by H-root method: comparison
      between open micro-channels and conventional packed columns.
AB  - This communication compares the accuracy of a micro open parallel plate system
      (microOPPS) with a conventional packed column for predicting isotherm data by
      using the H-root method (HRM). HRM is restricted to compounds obeying the
      Langmuir isotherm model. The performance of the two chromatographic systems was
      simulated by using comprehensive mathematical models. Operating conditions were
      varied and their effects on the accuracy of predictions was evaluated. Better
      accuracy in the isotherm predictions was obtained with the packed column due to
      its higher efficiency. However, good predictions can be obtained with the
      microOPPS with the advantage of significantly lower sample consumption.

PMID- 15861806
TI  - Preparative isolation and purification of germacrone and curdione from the
      essential oil of the rhizomes of Curcuma wenyujin by high-speed counter-current
      chromatography.
AB  - High-speed counter-current chromatography (HSCCC) was applied to isolate and
      purify bioactive compounds in the essential oil of the rhizomes of Curcuma
      wenyujin. Two sesquiterpenes germacrone and curdione were successfully isolated
      and purified using two-phase solvent system composed of petroleum ether-ethanol
      diethyl ether-water (5/4/0.5/1, v/v) in tail to head elution mode. 62 mg of
      germacrone and 93 mg of curdione were obtained from 658 mg of the essential oil
      each at over 95% purity. Their structures were identified by 1H NMR and EI MS.

PMID- 15861807
TI  - Isolation of quercetin-3-O-L-rhamnoside from Acer truncatum Bunge by high-speed
      counter-current chromatography.
AB  - Preparative high-speed counter-current chromatography (HSCCC) was successfully
      used for isolation and purification of quercetin-3-O-L-rhamnoside from the ethyl
      acetate extract of the leaves of Acer truncatum Bunge using a two-phase-system
      composed of ethyl acetate-ethanol-water at a volume ratio of 5:1:5 (v/v/v). In a
      single operation, 41.9mg of quercetin-3-O-L-rhamnoside was obtained from 366mg of
      the crude extract. High-performance liquid chromatography (HPLC) analyses of the
      CCC fraction revealed that the purity of quercetin-3-O-L-rhamnoside was over 96%.
      Its structure was identified by MS, 1H NMR and 13C NMR. Quercetin-3-O-L
      rhamnoside was obtained from this plant for the first time.

PMID- 15861808
TI  - One-step purification of alpha-amylase from the cultivation supernatant of
      recombinant bacillus subtilis by high-speed counter-current chromatography with
      aqueous polymer two-phase systems.
AB  - Purification of alpha-amylase from the cultivation supernatant of recombinant
      Bacillus subtilis by high-speed counter-current chromatography (HSCCC) in
      polyethylene glycol (PEG) 4000-inorganic salt aqueous polymer two-phase systems
      was studied. The effects of sodium chloride concentration on the partition
      coefficients of alpha-amylase and total protein were respectively tested in
      PEG4000-phosphate and PEG4000-citrate aqueous polymer two-phase systems to find
      the proper range of sodium chloride concentration for the HSCCC purification of
      alpha-amylase. Alpha-amylase was purified from the cultivation supernatant by
      HSCCC in PEG4000-phosphate system containing 2% (w/w) sodium chloride, yet with
      considerable loss of activity. PEG4000-citrate aqueous polymer two-phase system
      containing 2% (w/w) sodium chloride and supplemented with 0.56% (w/w) CaCl2 as
      protective agent was then successfully applied to purify alpha-amylase from
      cultivation supernatant by HSCCC to homogeneity and significantly increased the
      recovery of alpha-amylase activity from around 30 to 73.1%.

PMID- 15861809
TI  - Improved method for analyzing estrogens in water by liquid chromatography
      electrospray mass spectrometry.
AB  - An improved LC-electrospray ionization MS method was established for four
      estrogens (17beta-estradiol (E2), estriol (E3), estrone (E1), and ethynyl
      estradiol (EE)) in environmental water. Almost complete separation of all
      estrogens was achieved on a phenyl column with methanol/water as the mobile
      phase. Quantification was achieved in the negative ionization mode using selected
      ion monitoring. The instrumental detection limits were 20-30 ng/l for the four
      analytes. In Milli-Q spiked water, the recoveries of the four estrogens were 72
      81%, which was similar to those found for river water spiked with the
      corresponding deuterated estrogens. The detection limits for the four estrogens
      in river water were 0.1-0.2 ng/l. The method was used to detect residual
      estrogens in the Tonghui River, which receives water from a municipal sewage
      treatment plant in Beijing; E1 (1.1 ng/l) and E2 (0.2 ng/l) were detected.

PMID- 15861810
TI  - Simplified multiple headspace extraction gas chromatographic technique for
      determination of monomer solubility in water.
AB  - This paper reports an improved headspace gas chromatographic (GC) technique for
      determination of monomer solubilities in water. The method is based on a multiple
      headspace extraction GC technique developed previously [X.S. Chai, Q.X. Hou, F.J.
      Schork, J. Appl. Polym. Sci., in press], but with the major modification in the
      method calibration technique. As a result, only a few iterations of headspace
      extraction and GC measurement are required, which avoids the "exhaustive"
      headspace extraction, and thus the experimental time for each analysis. For
      highly insoluble monomers, effort must be made to minimize adsorption in the
      headspace sampling channel, transportation conduit and capillary column by using
      higher operating temperature and a short capillary column in the headspace
      sampler and GC system. For highly water soluble monomers, a new calibration
      method is proposed. The combinations of these technique modifications results in
      a method that is simple, rapid and automated. While the current focus of the
      authors is on the determination of monomer solubility in aqueous solutions, the
      method should be applicable to determination of solubility of any organic in
      water.

PMID- 15861811
TI  - Zentralblatt fur Bakteriologie-100 years ago the cultural differentiation between
      typhoid bacilli and Bacterium coli: Endo's agar started its triumphal march into
      the laboratories.

PMID- 15861812
TI  - Lactobacilli - bacteria-host interactions with special regard to the urogenital
      tract.
AB  - Lactobacilli are part of the commensal human mucosal flora. Their application as
      probiotics in dairy products such as yoghurt has increased during the last
      century since a health promoting effect has been reported. Much work has been
      done to study the effects of these bacteria on the immune system and epithelial
      cells, mainly focused on the intestinal mucosa as the field of first contact.
      This review is aimed to present and discuss results concerning interactions of
      lactobacilli and immune system or epithelial cells with focus to urogenital
      mucosa.

PMID- 15861813
TI  - Transcriptional regulation of high pathogenicity island iron uptake genes by
      YbtA.
AB  - A large group of Enterobacteriaceae, including members of the genus Yersinia,
      produce the extracellular siderophore yersiniabactin enabling them to multiply
      under iron-depleted conditions. Genes, involved in yersiniabactin synthesis,
      transport and regulation are clustered in the high pathogenicity island (HPI).
      YbtA, an AraC-like transcriptional regulator, is presumed to be the central
      regulator of yersiniabactin production together with the ferric uptake regulator
      Fur. In this work, we identified the transcriptional start points of YbtA
      regulated promoters of the HPI by primer extension, purified homogeneous YbtA and
      defined the YbtA-binding sites by DNaseI footprint analysis in ybtA, fyuA, irp6,
      and irp2 promoters. Besides of the anticipated pair repeats RS1 and RS2 in each
      promoter, we identified an additional YbtA-binding site designated RS3 in the
      divergently transcribed ybtA/irp6 promoter. Also, comparing ybtA/irp6 promoters
      of Y. enterocolitica and Y. pestis, we found that a 125-bp ERIC element insertion
      in the RS2 sequence of the Y. enterocolitica ybtA/irp6 promoter might increase
      YbtA expression, but did not affect expression of Irp6.

PMID- 15861814
TI  - Diversity of virulence patterns among shiga toxin-producing Escherichia coli from
      human clinical cases-need for more detailed diagnostics.
AB  - Intestinal infections due to shiga toxin-producing Escherichia coli bacteria
      (STEC) reveal a broad range of clinical symptoms and a large scale of virulence
      properties of the respective pathogens. The question whether all STEC variants or
      only a particular group of them need to be considered for clinical and
      epidemiological purposes was answered throughout this study. Using the PCR
      technique for the identification of 25 different virulence-associated genes, 266
      E. coli strains belonging to 81 different E. coli serotypes from various clinical
      origins were investigated. A great genetic diversity of the virulence properties
      and a broad range of virulence marker combinations have been identified. However,
      distinct virulence marker combinations (e.g. Stx2/LEE/pO157 as well as
      Stx2dac/pO113) were found to be associated with the same notified clinical
      symptoms (e.g. HUS). Such an association speaks either for the "shiga toxin-only
      concept" or for several redundant, but clinically or epidemiologically important
      virulence properties.

PMID- 15861815
TI  - Evaluation of custom-made DNA microarrays for multilocus sequence typing of
      Neisseria meningitidis.
AB  - Multilocus sequence typing (MLST) has become the gold standard for typing of a
      variety of bacterial and fungal micro-organisms. Others recently reported the
      successful use of the tiling DNA array technology to sequence-type Staphylococcus
      aureus. We now evaluated microarrays based on polymorphism-directed
      oligonucleotide design for typing of Neisseria meningitidis. The rationale behind
      this approach was to minimize the number of microarray probes by exploiting the
      comprehensive knowledge of polymorphisms combined in the Neisseria MLST website.
      Initial experiments using model oligonucleotides of 28-32 base-pairs in length
      revealed that the hybridization protocols used were highly specific. However,
      despite of several optimization steps, the rate of misidentification of
      oligonucleotides remained > 1.8% in consecutive validation experiments using
      arrays representing the genetic diversity at three MLST loci. We assume that the
      high density of polymorphic sites and the extensive GC-content variations at N.
      meningitidis MLST loci hinder the successful implementation of MLST microarrays
      based on polymorphism-directed oligonucleotide design.

PMID- 15861816
TI  - Rapid detection and identification of pathogens in blood cultures by fluorescence
      in situ hybridization and flow cytometry.
AB  - Septicemia is one of the leading causes of death in hospitalized patients. The
      timely detection and identification of microorganisms from the patient's blood
      has great diagnostic, prognostic and economic significance. Fluorescence in situ
      hybridization (FISH) with rRNA-targeted oligonucleotide probes has been proven to
      be a fast method for the identification of human pathogenic bacteria and yeasts.
      Data presented herein reveal that the combination of FISH and flow cytometry (FC
      FISH) is a rapid and reliable technique for identification of pathogens (Gram
      negative rods, Candida spp.) directly from blood cultures without further
      cultivation and biotyping. Moreover, detection of growing pathogens (e.g.,
      Stenotrophomonas maltophilia) in blood cultures is achieved more rapidly by FC
      FISH compared to standard detection methods. Therefore, FC-FISH allows rapid
      detection and identification of pathogens in blood cultures.

PMID- 15861817
TI  - The phosphatidylinositol 3-kinase Vps34p of the human pathogenic yeast Candida
      albicans is a multifunctional protein that interacts with the putative vacuolar
      H+ -ATPase subunit Vma7p.
AB  - The phosphatidylinositol 3-kinase Vps34p of Candida albicans participates in
      protein transport and in virulence. In order to characterize the functional link
      between these two activities we searched for proteins interacting with C.
      albicans Vps34p and demonstrate physical interaction of Vps34p with the subunit
      of the vacuolar H+ -ATPase Vma7p. The interaction initially observed in a yeast
      two-hybrid system was confirmed in vitro with recombinant proteins. Functional
      assays show that the Vps34p protein is necessary for vacuolar acidification and
      growth at alkaline pH. In addition, the vps34 null mutant of C. albicans shows
      defective autophagocytosis. The relevance of these functions for virulence of C.
      albicans is discussed.

PMID- 15861818
TI  - Ecological time-series analysis through structural modelling with latent
      constructs: concepts, methods and applications.
AB  - Time-series analyses in ecology usually involve the use of autoregressive
      modelling through direct and/or delayed difference equations, which severely
      restricts the ability of the modeler to structure complex causal relationships
      within a multivariate frame. This is especially problematic in the field of
      population regulation, where the proximate and ultimate causes of fluctuations in
      population size have been hotly debated for decades. Here it is shown that this
      debate can benefit from the implementation of structural modelling with latent
      constructs (SEM) to time-series analysis in ecology. A nonparametric bootstrap
      scheme illustrates how this modelling approach can circumvent some problems posed
      by the climate-ecology interface. Stochastic Monte Carlo simulation is further
      used to assess the effects of increasing time-series length and different
      parameter estimation methods on the performance of several model fit indexes.
      Throughout, the advantages and limitations of the SEM method are highlighted.

PMID- 15861819
TI  - A tunable multivariable nonlinear robust observer for biological systems.
AB  - This paper presents a robust nonlinear asymptotic observer with adjustable
      convergence rate with a great potential of applicability for biological systems
      in which the main state variables are difficult and expensive to measure or such
      measurements do not exist. This observer scheme is based on the classical
      asymptotic observer, which is modified to allow the tuning of the convergence
      rate. It is shown that the proposed observer provides fast and satisfactory
      estimates when facing load disturbances, system failures and parameter
      uncertainty while maintaining the excellent robustness and stability properties
      of the classical asymptotic observer. The implementation of the tunable observer
      is carried out by numerical simulations of a mathematical model of an anaerobic
      digestion process used for wastewater treatment. The key results are examined and
      further developed.

PMID- 15861820
TI  - Mathematical model for optimal control in wastewater discharges: the global
      performance.
AB  - In this work we show how mathematical models and optimal control techniques can
      help us to solve some problems of environmental engineering, more precisely,
      water pollution problems arising from wastewater discharges into coastal areas or
      rivers. We deal with a complete two-dimensional mathematical model for the
      evolution of pollutant concentration in a shallow water domain. By integrating
      this model we obtain a zero-dimensional one and we use it to study the global
      performance of the system in a realistic situation. Finally, by using the two
      dimensional model, we recall two optimal control problems related to the
      wastewater disposal problem.

PMID- 15861821
TI  - The stabilizability of a controlled system describing the dynamics of a fishery.
AB  - This work presents two stock-effort dynamical models describing the evolution of
      a fish population growing and moving between two fishing zones, on which it is
      harvested by a fishing fleet, distributed on the two zones. The first model
      corresponds to the case of constant displacement rates of the fishing effort, and
      the second one to fish stock-dependent displacement rates. In equations of the
      fishing efforts, a control function is introduced as the proportion of the
      revenue to be invested, for each fleet. The stabilizability analysis of the
      aggregated model, in the neighborhood of the equilibrium point, enables the
      determination of a Lyapunov function, which ensures the existence of a
      stabilizing discontinuous feedback for this model. This enables us to control the
      system and to lead, in an uniform way, any solution of this system towards this
      desired equilibrium point.

PMID- 15861822
TI  - Optimal strategy for structured model of fishing problem.
AB  - In this work we study a structured fishing model, basically displaying the two
      stages of the ages of a fish population, which are in our case juvenile, and
      adults. We associate to this model the maximization of the total discounted net
      revenues derived by the exploitation of the stock. The exploitation strategy of
      the optimal control problem is then developed and presented.

PMID- 15861823
TI  - Can marine protected areas enhance both economic and biological situations?
AB  - This paper investigates impacts of the creation of Marine Protected Areas (MPAs),
      in both economic and biological perspectives. The economic indicator is defined
      as the sum of discounted benefits derived from exploitation of the resource in
      the fishery sector, assumed to be optimally managed. The biological indicator is
      taken as the stock density of the resource. The basic fishery model (C.W. Clark,
      Mathematical Bioeconomics: The Optimal Management of Renewable Resources, second
      ed., John Wiley and Sons, New York, 1990) will serve as a convenient benchmark in
      comparing results with those that are derived from a model of two patchy
      populations (cf. R. Hannesson, Marine reserves: what would they accomplish, Mar.
      Resour. Econ. 13 (1998) 159). In the latter, a crucial characteristic is the
      migration coefficient with describes biological linkages between protected and
      unprotected areas. A set of situations where both economic and biological
      criteria are enhanced, after introducing a MPA, is presented. These results are
      obtained with the help of numerical simulations.

PMID- 15861824
TI  - A model for the upstream motion of elvers in the Adour River.
AB  - The aim of this paper is contributing to the study of the exploitation of the
      European eel (Anguilla anguilla) in the basin of the French river 'Adour'. This
      exploitation constitutes the basis of the economy of local professional
      fishermen, who have recently noticed a diminution of the hunting of elvers. In
      order to design a sustainable exploitation strategy, we must know as much as
      possible about eel life cycle. For that purpose, we build a model to describe a
      phase of eels evolution, their migration upstream the river. Our model is based
      on the biological details of eels behaviour and constitutes a virtual laboratory,
      useful to test different hypotheses about eels migration.

PMID- 15861825
TI  - Fuelwood harvesting in Niger and a generalization of Faustmann's formula.
AB  - In some forests of Niger where 'controlled rural markets' have been organized,
      fuelwood is harvested following a policy of the form: every T year, cut the dead
      trees and those live trees which have a diameter greater than D. Dead trees
      generally form the main part of the harvest. In this paper, we present a simple
      continuous time model for the management of these uneven-aged stands subject to a
      high natural death rate alpha, and we derive a formula for the cycle length and
      the diameter optimizing the discounted income over an infinite horizon.
      Faustmann's classical formula for even-aged stands corresponds to the limit alpha
      --> 0 and D = 0 (clear-cut).

PMID- 15861826
TI  - Numerical study of size-structured population models: a case of Gambussia
      affinis.
AB  - We study, from a numerical point of view, some properties of a model which
      describes the evolution of a population of Gambussia affinis. Our model includes
      sufficiently smooth vital functions. First we select, among four numerical
      methods of second order, the most appropriate in terms of adaptation to the
      problem. The most efficient method also reveals new properties of the model for
      long times, such as the tendency to periodicity, obtained with different initial
      conditions. We also discuss some advantages and deficiencies of the model.

PMID- 15861827
TI  - Evolutionary games with variable payoffs.
AB  - Matrix games, defined by a set of strategies and a corresponding matrix of
      payoffs, are commonly used to model animal populations because they are both
      simple and generate meaningful results. It is generally assumed that payoffs are
      independent of time. However, the timing of contests in real populations may have
      a marked effect on the value of rewards. We consider matrix games where the
      payoffs are functions of time. Rules are found which hold in this more general
      situation, and the complexity of possible behaviour is underlined by
      demonstrating other conditions which do not hold and an illustrative game.

PMID- 15861828
TI  - Subsurface damage in some single crystalline optical materials.
AB  - We present a nondestructive method for estimating the depth of subsurface damage
      (SSD) in some single crystalline optical materials (silicon, lithium niobate,
      calcium fluoride, magnesium fluoride, and sapphire); the method is established by
      correlating surface microroughness measurements, specifically, the peak-to-valley
      (p-v) microroughness, to the depth of SSD found by a novel destructive method.
      Previous methods for directly determining the depth of SSD may be insufficient
      when applied to single crystals that are very soft or very hard. Our novel
      destructive technique uses magnetorheological finishing to polish spots onto a
      ground surface. We find that p-v surface microroughness, appropriately scaled,
      gives an upper bound to SSD. Our data suggest that SSD in the single crystalline
      optical materials included in our study (deterministically microground, lapped,
      and sawed) is always less than 1.4 times the p-v surface microroughness found by
      white-light interferometry. We also discuss another way of estimating SSD based
      on the abrasive size used.

PMID- 15861829
TI  - Multiwindowed defocused electronic speckle photographic system for tilt
      measurement.
AB  - Defocused speckle photography has long been used to measure rotations of rough
      surfaces. By addition of a suitably perforated mask, some measurement properties,
      such as range and lateral resolution, may be changed at will. In particular, the
      maximum measurable tilt can be significantly increased, although at the expense
      of poorer lateral resolution. Advantages of this compared with previously
      described techniques include independent tuning of speckle size and optical
      system aperture and greater adaptability to various measuring needs. The benefits
      and disadvantages of the new and old techniques are thoroughly compared.

PMID- 15861830
TI  - Gold-coated copper cone detector as a new standard detector for F2 laser
      radiation at 157 nm.
AB  - A new standard detector for high-accuracy measurements of F2 laser radiation at
      157 nm is presented. This gold-coated copper cone detector permits the
      measurement of average powers up to 2 W with an uncertainty of approximately 1%.
      To the best of our knowledge, this is the first highly accurate standard detector
      for F2 laser radiation for this power level. It is fully characterized according
      to Guide to the Expression of Uncertainty in Measurement of the International
      Organization for Standardization and is connected to the calibration chain for
      laser radiation established by the German National Metrology Institute.

PMID- 15861831
TI  - In vivo measurement of lower back deformations with Fourier-transform
      profilometry.
AB  - Through the variation of their cross sections, the in vivo response of lower back
      muscles to low loading in an upright seated posture is explored by the Fourier
      transform profilometry technique. The maximization of its sensitivity allows us
      to reach an adequate resolution for the evaluation of low-back displacements.
      Refinements of the fringe pattern analysis permit the minimization of errors. The
      experiments show an asymmetric distribution of the displacement during head
      rotation movements. Significant contribution of the lower back to grasping
      exertions is also observed. These results are thought to be useful for early
      defect detection in the lower back.

PMID- 15861832
TI  - Laser-Doppler velocity profile sensor with submicrometer spatial resolution that
      employs fiber optics and a diffractive lens.
AB  - We report a novel laser-Doppler velocity profile sensor for microfluidic and
      nanofluidic applications and turbulence research. The sensors design is based on
      wavelength-division multiplexing. The high dispersion of a diffractive lens is
      used to generate a measurement volume with convergent and divergent interference
      fringes by means of two laser wavelengths. Evaluation of the scattered light from
      tracers allows velocity gradients to be measured in flows with submicrometer
      spatial resolution inside a measurement volume of 700-microm length. Using
      diffraction optics and fiber optics, we achieved a miniaturized and robust
      velocity profile sensor for highly resolved velocity measurements.

PMID- 15861833
TI  - Videokeratoscope for accurate and detailed measurement of the cornea surface.
AB  - A videokeratoscope based on the imaging of a gridlike pattern is introduced.
      Unlike conventional videokeratoscopes that rely on Placido disks, the new
      measurement principle allows an exact reconstruction of the surface and the
      display of fine details. The experimental instrument was tested on precision
      glass spheres; the maximum error of the height data was less than 3 microm. The
      sensitivity and the potential to resolve fine details were demonstrated with
      irregular surfaces of specially prepared contact lenses. Structures with height
      deviations of 0.1 microm are well identifiable. The eyes of 18 individuals were
      investigated, and fine structures were found on these cornea surfaces.
      Conventional videokeratoscopes do not resolve such detail.

PMID- 15861834
TI  - Development of a bioengineered tissue model and its application in the
      investigation of the depth selectivity of polarization gating.
AB  - Understanding the propagation of polarized light in tissue is crucial for a
      number of biomedical optics applications. Here we report the development of a
      bioengineered connective tissue model fabricated by the combination of
      scaffolding and cross-linking techniques to study light transport in biological
      tissue. It demonstrates great similarity to real connective tissue in its optical
      properties as well as microarchitecture. Moreover, the optical properties of the
      model can be reproducibly controlled. As an example, we report the utilization of
      this model to study the effect of epithelium and the underlying connective tissue
      on the depth selectivity of polarization gating.

PMID- 15861835
TI  - Statistical approach for detection and localization of a fluorescing mouse tumor
      in Intralipid.
AB  - We present a method for detecting and localizing a fluorescing tumor obscured
      underneath several millimeters of a multiply scattering, homogeneous medium from
      fluorescence measurements made above the surface. Using a statistical model of
      the measurement system, we develop approaches for detection by use of a binary
      hypothesis testing approach and localization by use of maximum-likelihood
      estimation. We also compute the probability of tumor detection and the Cramer-Rao
      lower bound for the localization estimate error, which are performance metrics
      that could potentially be optimized in an experimental design. We validate the
      methods in an experimental study involving an excised mouse tumor tagged with a
      new folate-indocyanine dye and obscured under a tissue-simulating lipid
      suspension.

PMID- 15861836
TI  - Improved analysis on the viewing angle of integral imaging.
AB  - There have already been several analyses about the viewing angle of integral
      imaging (InIm). However, they can be applied only under the assumption that the
      original image is merely a single point source and are not suitable for
      application to an actual condition. We propose an improved analysis based on the
      actual InIm image, not on a single point source. It is possible to analyze and
      predict the viewing angle of an InIm system with good accuracy with the new
      analytic method because almost all the parameters of the InIm system such as the
      size and focal length of the lens array, image distance, the size and resolution
      of the image, and the location of the observers are included in this analysis.

PMID- 15861837
TI  - Prediction of light-transmission losses in plastic optical fibers.
AB  - A theoretical expression is derived, based on a geometrical optics approach, with
      which to predict light-transmission losses in multimode plastic optical fibers
      for office or home lighting. Two types of optical ray arrangement, meridional ray
      and skew ray, are evaluated, and five loss mechanisms are identified and
      considered. The meridional arrangement results in a lower overall loss of light
      than the skew ray arrangement. The theoretical results were compared with
      experimental measurements taken for a 0.5-cm-diameter polymer optical fiber. For
      optical rays entering the fiber at incident angles of less than 20 degrees, the
      theoretical results are in good agreement with the empirical results.

PMID- 15861838
TI  - Optical performance at the thermodynamic limit with tailored imaging designs.
AB  - Ultracompact concentrators and illuminators that approach the thermodynamic limit
      to optical performance can be realized with purely imaging strategies. We explore
      two-stage reflector systems where each optical surface is tailored to eliminate
      one order of aberration--the so-called aplanatic designs. The contours are
      monotonic functions that can be expressed analytically, which are important for
      the facilitation of optimization studies and practical fabrication. The radiative
      performance of the devices presented is competitive with, and even superior to,
      that of high-flux nonimaging systems. Sample results of practical value in solar
      concentration and light collimation are presented for systems that cover a wide
      range of numerical aperture.

PMID- 15861839
TI  - Surface plasmon excitation on a single subwavelength hole in a metallic sheet.
AB  - The diffraction of light by a single subwavelength hole in a highly conductive
      metallic sheet is analyzed with a recently developed differential theory that is
      able to plot the nearly electromagnetic field. Using rigorous electromagnetic and
      phenomenological analysis, we show that a single subwavelength hole can excite
      surface-plasmon resonance that contributes greatly to extraordinary transmission.

PMID- 15861840
TI  - Light scattering by an infinite circular cylinder immersed in an absorbing
      medium.
AB  - Analytic solutions are developed for the single-scattering properties of an
      infinite dielectric cylinder embedded in an absorbing medium with normal
      incidence, which include extinction, scattering and absorption efficiencies, the
      scattering phase function, and the asymmetry factor. The extinction and
      scattering efficiencies are derived by the near-field solutions at the surface of
      the particle. The normalized scattering phase function is obtained by use of the
      far-field approximation. Computational results show that, although the absorbing
      medium significantly reduces the scattering efficiency, it has little effect on
      absorption efficiency. The absorbing medium can significantly change the
      conventional phase function. The absorbing medium also strongly affects the
      polarization of the scattered light. However, for large absorbing particles the
      degrees of polarization change little with the medium's absorption. This implies
      that, if the transmitting lights are strongly weakened inside the particle, the
      scattered polarized lights can be used to identify objects even when the
      absorption property of the host medium is unknown, which is important for both
      active and passive remote sensing.

PMID- 15861841
TI  - Nonpolarizing and polarizing filter design.
AB  - We describe a nonpolarizing filter design at oblique incidence and a polarizing
      filter design at normal incidence that use a uniaxially anisotropic layer. The
      phase thicknesses and the optical admittances of the layers are compensated for
      by the birefringent properties of a thin film at oblique incidence. This concept
      can be applied to the design of nonpolarizing bandpass and edge filters at
      oblique incidence and of polarizing beam splitters at normal incidence. Besides,
      the dependence of narrow-bandpass filters on normal incidence is discussed.

PMID- 15861842
TI  - Determination of the size and structure of an X-pinch x-ray source from the
      diffraction pattern produced by microfabricated slits.
AB  - X-pinch plasma emits subnanosecond bursts of x rays in the 3-10-keV energy range
      from a small source. As such, it has been used for high-resolution point
      projection imaging of small, dense, rapidly changing plasmas as well as for
      submillimeter-thick biological samples. In addition to the effect of source size
      on geometric resolution, a small source size can also provide high spatial
      coherence of x rays, enabling the rays to be used for imaging weakly absorbing
      objects with excellent spatial resolution by a method called phase-contrast
      imaging. To determine the source size, we microfabricated gold slits and imaged
      them in a point-projection radiography configuration. The shape of the shadow
      image pattern depends on the source size and energy band of the x rays, the shape
      and material used for the slits, and the geometry of the experiment. Experimental
      results have been compared with wave-optics calculations of the expected image
      pattern as a function of all the parameters listed above. For example, assuming a
      Gaussiansource distribution, an effective source size in 2.5-4.1 A radiation (1 A
      = 0.1 nm) of 1.2 +/- 0.5 microm (full width at half-maximum) was determined for a
      20-microm Mo wire X pinch. Characterization of the size and structure of the x
      ray bursts from X pinches by the use of different wire materials and different
      slit structures is made.

PMID- 15861843
TI  - Fringe-density estimation by continuous wavelet transform.
AB  - For many phase extraction algorithms, a priori knowledge of a fringe-pattern
      density distribution is beneficial for later processing. A fringe-density
      estimation method based on a continuous wavelet transform (CWT) is proposed. For
      a one-dimensional signal the instantaneous frequency detected at the CWT ridge is
      directly adopted as a measure of the local fringe density. For a two-dimensional
      signal the instantaneous frequency components in both the x and the y directions
      are detected. Their reliability is evaluated by the CWT coefficient magnitude,
      based on which an approximate density value is given. The capability for noise
      reduction and the accuracy of the method are discussed.

PMID- 15861844
TI  - Image identification system based on an optical broadcast neural network
      processor.
AB  - We describe the implementation of a vision system based on a hardware neural
      processor. The architecture of the neural network processor has been designed to
      exploit the computational characteristics of electronics and the communication
      characteristics of optics in an optimal manner, thus it is based on an optical
      broadcast of input signals to a dense array of processing elements. The vision
      system has been built by use of a prototype implementation of a neural network
      processor with discrete optic and optoelectronic devices. It has been adapted to
      work as a Hamming classifier of the images taken with a 128 x 128 complementary
      metal-oxide semiconductor image sensor. Its results, performance characteristics
      of the image classification system, and an analysis of its scalability in size
      and speed, with the improvement of the optoelectronic neural processor, are
      presented.

PMID- 15861845
TI  - Form-birefringence structure fabrication in GaAs by use of SU-8 as a dry-etching
      mask.
AB  - A thin layer of a SU-8 submicrometer pattern produced by holographic lithography
      was directly used as the dry-etching mask in a chemically assisted ion-beam
      etching system. With optimized etching parameters, etching selectivity of 7:1 was
      achieved together with a smooth vertical profile. As an application, a half
      wavelength retardation plate for a 1.55-microm wavelength was produced and
      evaluated.

PMID- 15861846
TI  - High-birefringence fiber loop mirrors and their applications as sensors.
AB  - The reflection and transmission characteristics of a high-birefringence fiber
      loop mirror (HiBi-FLM), which is composed of a standard fiber coupler and one
      section or multisection high-birefringence fibers (HBFs), are analyzed and
      discussed in detail. Theoretical reflectivity and transmissivity expressions for
      HiBi-FLMs with one-, two-, and three-section HBFs were obtained. The procedure
      for calculating reflectivity and transmissivity for HiBi-FLMs with n-section HBFs
      is given. Experimental results have verified the theoretical model. The basic
      characteristics of the one-section HiBi-FLM when strain and high temperature are
      applied to HBFs were analyzed and investigated theoretically and experimentally.
      The experimental results are in good agreement with the theoretical analysis.
      Furthermore, a strain--temperature sensor that makes use of those
      characteristics, which is new for applications of HiBi-FLMs, has been proposed
      and demonstrated.

PMID- 15861847
TI  - Dispersion characteristics of segmented optical fibers.
AB  - A direct scalar two-dimensional routine based on the method of lines is
      implemented to analyze the dispersion characteristics of segmented fibers. In
      this kind of structure, dispersion control in a simple profile is achieved by
      variations in the filling ratio of the coaxiallike structure.

PMID- 15861848
TI  - Broadband, lossless, dispersion-compensating asymmetrical twin-core fiber design
      with flat-gain Raman amplification.
AB  - We report here a broadband, lossless, dispersion-compensating asymmetrical twin
      core fiber design with flat-gain Raman amplification that uses a single pump.
      Simulations show that broadband Raman amplification, with +/- 0.1-dB gain ripple,
      is achievable over a 31-nm bandwidth (1504-1535 nm) by use of a single pump.
      Amplifier characteristics have been modeled, with the effects of wavelength
      dependent splice and background attenuation loss taken into account. The fiber
      also has a high negative-dispersion coefficient [-230 to -330 ps/(km nm)] over
      the operating wavelength range and, hence, only 12.5 km of this fiber can
      compensate for an accumulated dispersion of 240 km of standard transmission
      fiber. The device is thus proposed as a lossless dispersion-compensating module
      wherein lossless operation is achieved by use of inherently gain-flattened Raman
      amplification.

PMID- 15861849
TI  - Planar waveguide-based silica-polymer hybrid variable optical attenuator and its
      associated polymers.
AB  - We have proposed a silica-polymer hybrid variable optical attenuator that we made
      by creating two trenches along the core of a straight silica planar waveguide and
      filling the trenches with a polymer. The polymer, which had a superhigh thermo
      optic coefficient, was specially designed and developed in this study to lower
      the power consumption of the device. We achieved a maximum attenuation of -29 dB
      for the device by changing the polymer's temperature by only 7 degrees C. The
      device has a very low power consumption at 2-3 mW/channel, making it a good
      candidate for integration with arrayed waveguide gratings.

PMID- 15861850
TI  - Fabrication of compact turning mirrors in silicon-on-insulator materials.
AB  - A turning mirror is a key component in compact optical waveguide devices and high
      density integrated optics. An improved two-step method for fabrication of high
      quality, compact turning mirrors in silicon-on-insulator materials is proposed.
      First, inductively coupled plasma etching is applied to produce the turning
      mirror, which keeps the turning mirror compact; then silicon wet anisotropic
      etching is applied to enhance the quality of the turning mirror by of its
      polishing surface, correcting its orientation, and improving the verticality. The
      shape of the turning mirror fabricated by the two-step method is hexagonal or
      octagonal, matching the optical field of the rib waveguide well. A large
      effective mirror size to reflect light waves and reduced shrinkage of the mirror
      size during etching guarantee that a mirror produced by this two-step method will
      be more compact than previously designed mirrors.

PMID- 15861851
TI  - Tenth-order rational-harmonic frequency multiplication and detuning of optical
      pulse injection-locked erbium-doped fiber laser.
AB  - The jitter and frequency-detuning dynamics of a 10-GHz rational-harmonic
      frequency-multiplied pulse train generated from an erbium-doped fiber laser
      (EDFL) is studied. The EDFL is self-feedback seeded and optically injection
      locked by a gain-switched laser diode (GSLD) with a pulse width and an average
      power of 17.6 ps and 0.2 mW, respectively, at a repetition frequency of 1 GHz.
      The repetition frequency of the optical pulse train can be tenth-order multiplied
      by a slight detuning of the repetition frequency of the GSLD to match the
      rational-harmonic injection-locked condition of the EDFL. As the repetition
      frequency is multiplied from 1 to 10 GHz, the peak power, the pulse width, and
      the frequency-detuning bandwidth of the injection-locked EDFL pulses decrease
      from 1.2 to 0.3 W, from 40 to 21 ps, and from 40 to 9 kHz, respectively. The
      timing jitter of the injection-locked EDFL repeated at 1 GHz remains unchanged (<
      0.5 ps) within the detuning bandwidth, which inevitably increases to 1.2 ps after
      tenth-order multiplication.

PMID- 15861852
TI  - Z-Beamlet: a multikilojoule, terawatt-class laser system.
AB  - A large-aperture (30-cm) kilojoule-class Nd:glass laser system known as Z-Beamlet
      has been constructed to perform x-ray radiography of high-energy-density science
      experiments conducted on the Z facility at Sandia National Laboratories,
      Albuquerque, New Mexico. The laser, operating with typical pulse durations from
      0.3 to 1.5 ns, employs a sequence of successively larger multipass amplifiers to
      achieve up to 3-kJ energy at 1054 nm. Large-aperture frequency conversion and
      long-distance beam transport can provide on-target energies of up to 1.5 kJ at
      527 nm.

PMID- 15861853
TI  - Optimum operation of femtosecond parametric oscillation of a noncollinear phase
      match in KTP.
AB  - For group-velocity (GV) matching, tunable femtosecond parametric oscillation must
      use noncollinear phase matching (PM). The tuning curves of femtosecond parametric
      oscillation are described; tuning can be continuous from the visible to the mid
      infrared. We demonstrate that GV matching and PM can be satisfied in type II PM
      for KTP. The effective nonlinear coefficient, the walk-off angles, the acceptance
      angles (a and theta(s)), the acceptance spectral width, and the duration of the
      output idler pulse are calculated. Consequently, optimum femtosecond parametric
      oscillation of noncollinear phase matching is obtained in KTP.

PMID- 15861854
TI  - Retrieval of vertical constituents and temperature profiles from passive
      submillimeter wave limb observations of the Martian atmosphere: a feasibility
      study.
AB  - The investigation of the Martian atmosphere is of key importance for an
      understanding of the planets present and past. Passive limb observations of
      thermal radiation at submillimeter wavelengths in the 320-350-GHz range by use of
      a state-of-the-art satellite receiver on a low Mars orbit allow important
      parameters such as the mixing ratios of H2O, HDO, 12CO, 13CO, O3, and H2O2 as
      well as the thermal profile to be retrieved with high precision and unprecedented
      vertical range and resolution, providing valuable information for better
      understanding of the planet's water cycle, atmospheric dynamics, and
      photochemistry. The feasibility of these kinds of measurement is demonstrated by
      means of model simulations based on realistic atmospheric, spectroscopic, and
      instrumental parameters. Temperature can be retrieved to approximately 90 km with
      half-scale height vertical resolution from single-scan measurements of emission
      lines of the long-lived species 12CO and 13CO. The global water-vapor
      distribution can be measured even under dry or wet conditions with good vertical
      resolution from the surface to approximately 45 km, and simultaneous observations
      of HDO allow useful information on the D/H ratio up to an altitude of
      approximately 30 km to be derived. The sensitivity of the limb-sounding technique
      also permits information on the photochemically important minor species O3, and
      H2O2 to be obtained. It is shown that spectral averaging may improve precision,
      altitude range, and resolution of the retrieved profiles. Other frequency bands
      are explored, and the 435-465-GHz range is suggested as a possible alternative to
      the 320-350-GHz range.

PMID- 15861855
TI  - Comparing distal and proximal techniques of saphenous nerve conduction study in
      healthy subjects.
AB  - For comparing distal and proximal techniques. To obtain saphenous nerve sensory
      response, 102 healthy subjects with mean age 43.1 years and mean Body Mass Index
      (BMI) 25.3 were studied. Both techniques performed by using surface electrodes.
      In distal technique recording site was anterior to medial malleolus and
      stimulator 14 cm proximal to it. In proximal technique stimulation performed on
      the medial aspect of the knee and response recorded from the leg, 14 cm distal to
      the cathode. In 204 studied nerves, response obtained in 145 nerves (71%) by
      distal technique, in 125 nerves (61%) by proximal technique and in 94 nerves
      (46%) by both techniques. In 176 nerves (86%) response obtained at least by one
      of two techniques. In men, response obtaining rate by proximal technique (90.5%)
      was higher than distal one (57%) (P < 0.0001) but in women this rate was 81% by
      distal technique and 41% by proximal technique (P < 0.0001). Distal technique was
      more successful than proximal in subjects with higher age (P < 0.05) and higher
      BMI (P < 0.001). In conclusion, for saphenous nerve conduction study in men, it
      is better to perform proximal technique primarily but in women distal technique
      is preferred. Performing the second technique when the first one is failed is
      suggested.

PMID- 15861856
TI  - Trigemino-cervical response in patients with amyotrophic lateral sclerosis.
AB  - PURPOSE: The trigemino-cervical response (TCR) was investigated in the patients
      with amyotrophic lateral sclerosis (ALS) to evaluate its effect for disclosing
      the bulbar involvement in this disorder. METHODS: We studied 100 normal subjects
      and 45 patients with ALS. In all normal subjects, stimulation of the infraorbital
      nerve on one side produced bilateral short latency waves, which consisted of a
      positive/negative wave described with the mean peak latency (P20/N30). The mean
      square root of the ratio between the amplitude of P20/N30 and the mean rectified
      surface EMG activity preceding the stimulus was described by A value. RESULTS:
      The latency of P20 in controls was 18.5 +/- 1.4 ms, N30 was 28.8 +/- 2.8 ms, and
      the A value was 1.6 +/- 0.5, respectively. In ALS patients, twelve showed absent,
      seventeen were delayed in the latencies, six were above normal asymmetry on two
      sides, and ten showed normal. The latency of P20 in ALS patients was 22.9 +/- 9.4
      ms, N30 was 33.7 +/- 11.2 ms, and the A value was 1.5 +/- 0.8, respectively. The
      parameters of the latencies of TCR between ALS patients and the normal controls
      were statistically different (P < 0.05). CONCLUSIONS: TCR can be reliably
      measured in all normal subjects and help in disclosing lower brainstem lesions in
      ALS patients, even without bulbar symptoms.

PMID- 15861857
TI  - Thalidomide therapy and polyneuropathy in myeloma patients.
AB  - Thalidomide is today an increasingly used therapy in advanced and refractory
      myeloma patients, especially in patients relapsing after high dose therapy. One
      important and well-known side effect of thalidomide is polyneuropathy (PNP). The
      purpose of this study was to investigate 1) how severe the thalidomide-induced
      PNP is in patients treated for myeloma 2) which neurophysiological tests and
      parameters are most sensitive in detecting the thalidomide-induced PNP and 3) how
      neuropathic symptoms correlate with neurophysiological changes. Twelve patients
      received thalidomide for treatment of relapsed multiple myeloma for at least 5
      months. Prior to the thalidomide treatment, all patients had been treated with
      chemotherapy including vincristine, and seven patients had also received
      cisplatin. PNP symptoms, clinical findings and neurophysiological tests before
      and after the therapy were evaluated. Prior to thalidomide treatment, 7 patients
      had minimal and one patient slight PNP. After thalidomide treatment, 4 patients
      had minimal, 4 patients slight, and 3 patients moderate PNP. Thalidomide-induced
      PNP mainly affected sensory myelinated axons, but also alpha motor neuron axons
      were affected to some extent. Thermal thresholds were not altered, indicating
      that thin myelinated and unmyelinated axons are spared. The most sensitive
      parameter for detecting thalidomide-induced PNP was the sensory nerve compound
      action potential amplitude. The neuropathic symptoms deteriorated significantly
      during the therapy, but clinically, no patient developed a disabling PNP that
      would have required interrupting the therapy. The neuropathic side effects of
      thalidomide seem to be acceptable in myeloma patients.

PMID- 15861858
TI  - Ulnar neuropathy at Guyon's canal: electrophysiological and surgical findings.
AB  - Published correlations between electrophysiological and surgical findings are
      relatively rare in cases of ulnar nerve compression at the wrist, compared to the
      more common compression of the ulnar nerve at the elbow. We describe a patient
      who presented with clinical and electrodiagnostic findings of a pure motor ulnar
      neuropathy involving the territory of the deep branch. Surgical exploration
      revealed that a ganglion cyst caused compression of the deep ulnar motor branch
      at Guyon's canal. This case illustrates the usefulness of electrodiagnostic
      studies in the localization of nerve entrapment prior to surgery.

PMID- 15861859
TI  - Comparison of Fourier and wavelet transform procedures for examining
      mechanomyographic and electromyographic frequency versus isokinetic torque
      relationships.
AB  - The purpose of this study was to compare the isokinetic torque-related patterns
      for mechanomyographic (MMG) and electromyographic (EMG) center frequency [wavelet
      center frequency (CF), mean power frequency (MPF), and median frequency (MDF)]
      determined by the fast Fourier transform (FFT) and discrete wavelet transform
      (DWT). Ten adults [mean +/- SD age = 22.0 +/- 3.4 yrs] performed submaximal to
      maximal, isokinetic muscle actions of the biceps brachii on a Cybex II
      dynamometer. For both MMG and EMG, the CF, MPF, and MDF values were
      intercorrelated at (r = 0.91-0.98). Quadratic models provided the best fit for
      the absolute and normalized CF, MPF, and MDF versus isokinetic torque
      relationships for MMG (R2 = 0.67-0.83) and EMG (R2 = 0.72-0.90). The similarities
      among the CF, MPF, and MDF patterns suggested that Fourier or wavelet transform
      procedures can be used to examine the patterns of MMG and EMG responses during
      dynamic muscle actions.

PMID- 15861860
TI  - Modulation of the tibial nerve H-reflex by mechanical stimulation of afferents in
      the lumbar spine.
AB  - The purpose of this study was to describe the convergence of afferent discharges
      from the ligament-muscular system of the lumbar spine to the segmentally-related
      gastrocnemius muscle. The subjects were 32 healthy, young volunteers recruited
      from a college student population. Afferent discharges from the ligament-muscular
      system of the lumbar spine were evoked by manually moving the trunk into either
      flexion (n = 16) or left lateral bending (n = 16) using a multi-directional
      adjustable treatment table (Zenith Cox Flexion Table). Using linear
      potentiometers affixed to the treatment table and interfaced with a computer data
      acquisition system, manual movements of the table were visually guided to
      generate passive trunk movements at velocities of 10 degrees, 20 degrees, and 40
      degrees per second. Tibial nerve H-reflex responses were recorded from the right
      gastrocnemius muscle as the trunk approached its end range of motion. Regardless
      of velocity for the flexion movement, the H/M(Max) ratio significantly decreased
      from 28.0% to 20.9% (p < .05). During lateral bending, the H/M(Max) ratio
      significantly decreased from 27.4% to 24.0% at velocities of 10 degrees and 20
      degrees per second (p < .05) with a subsequent decrease to 20.5% at a velocity of
      40 degrees per second (p < .05). The nature of these decreases in the H/M(Max)
      ratios across the different velocities during lateral bending significantly
      departed from linearity (p < .05). These data provide sufficient evidence to
      suggest that heteronymous conditioning effects from the ligament-muscular system
      of the lumbar spine during passive trunk movements attenuate alpha motoneuronal
      activity of the segmentally-related gastrocnemius muscle.

PMID- 15861861
TI  - Post-activation depression of the soleus H-reflex in stroke patients.
AB  - PURPOSE: We examined post-activation depression in 35 stroke patients and 10
      healthy subjects, and investigated whether their clinical symptoms were
      correlated to post-activation depression. METHODS: Post-activation depression of
      the soleus H-reflex evoked by electrical stimulation of the common peroneal nerve
      with supramaximal intensity of motor response on the tibialis anterior muscle.
      RESULTS: Post-activation depression was decreased on the affected side of the
      stroke patients. There was a significant difference between the affected and
      unaffected sides of the patients with post-activation depression, but no
      difference between the unaffected sides of the patients and healthy subjects. The
      presence of ankle clonus and the decrease in post-activation depression were
      correlated. CONCLUSION: Decreased post-activation depression in stroke patients
      suggests that a mechanism other than postsynaptic inhibition, such as reciprocal
      Ia inhibition and Ib inhibition, and presynaptic inhibition, may contribute to
      the exaggerated stretch reflexes, in particular, the manifestation of clonus.

PMID- 15861862
TI  - Prevalence and severity of carpal tunnel syndrome (CTS) during pregnancy.
AB  - Carpal Tunnel Syndrome (CTS) is the entrapment of Median nerve at wrist.
      Pregnancy can affect prevalence and severity of CTS. In this study frequency and
      severity of CTS in pregnancy was evaluated. In this study 100 pregnant women were
      evaluated by Hand symptoms, CTS provocation tests (Tinel and Phalen) and for
      definite diagnosis of CTS standard EDX studies were used. For this purpose
      sensory and motor distal latency of Median were measured and compared with ulnar
      nerve. 17% of pregnant women had CTS with 23.5% bilateral involvement and 17.5%
      severe CTS. Prevalence of hand symptom and clinical sign of CTS (phalen and tinel
      sign) were 36% and 26% respectively. Results indicated that prevalence of CTS in
      pregnant women was significant. Although hand signs and symptoms are useful, EDX
      study is more reliable.

PMID- 15861863
TI  - End-of-life care in West Virginia.

PMID- 15861864
TI  - ATV Accidents continue to be a major public health issue in West Virginia.
AB  - All-terrain vehicle (ATV) riding continues to be a major public health problem in
      West Virginia because the state leads the nation in the rate of deaths from ATV
      incidents and has significantly higher death rates than all five of the bordering
      states. Annually, there are 24 deaths a year in West Virginia due to ATV
      accidents and thousands of nonfatal injuries. Sporting events using ATVs such as
      motocross racing have added to the burden of caring for patients who are injured
      in recreational activities. We report a case study of 10 patients treated over an
      18-hour period in a state trauma center for injuries received while riding ATVs
      casually and in competition. The addition of these 10 patients to the other 108
      patients seen in the ED during this period totally disrupted patient flow, caused
      significant delays in care of the non-trauma patients, and tied up the Radiology
      Department and operating rooms for an extended period.

PMID- 15861865
TI  - Factors causing patients to delay seeking treatment after suffering a stroke.
AB  - Many studies have looked at issues surrounding why people delay in accessing
      healthcare after they have experienced a stroke, but no published studies on this
      subject have been conducted in West Virginia. To identify the factors causing
      patients to delay treatment for a stroke, we conducted a concurrent chart review
      of 64 acute stroke and TIA patients presenting at Charleston Area Medical Center
      from April 1, 2003 to July 21, 2003. Results showed that the majority of patients
      arrived beyond the critical three-hour limit for tissue plasminogen activator
      (tPA) medication. The patients who reported speech problems and confusion as
      their initial symptoms, those who lived within 15 miles of the hospital, and
      those who used ambulance transport, were most likely to arrive at the hospital in
      less than two hours. On the other hand, the patients who were less likely to
      arrive within two hours were those who were alone at symptom onset, those who had
      weakness as a prominent symptom, as well as those were younger and had commercial
      insurance. We recommend educating the community about the symptoms of stroke and
      focusing on the fact that stroke is a medical emergency and calling 911 is
      necessary.

PMID- 15861866
TI  - The prevalance of celiac disease in West Virginia.
AB  - Celiac disease (CD) has been long considered as a "European disease" that is
      rarely seen in the North America. Recent data has refuted this notion and
      suggested that celiac disease in the United States is as common as in Europe. The
      atypical clinical presentation of celiac disease was one of the major reasons
      implicated for the under-diagnosis of this disease in American children. In this
      report, we describe several case presentations of children with celiac disease in
      order to update primary care physicians on the pathophysiology, diagnosis,
      treatment, and prognosis of this increasingly prevalent disease.

PMID- 15861867
TI  - Porphyria cutanea tarda in a patient with HIV-infection.
AB  - Several recent reports have described porphyria cutanea tarda (PCT) occurring in
      patients with HIV infection. Current evidence suggests that HIV infection may
      impair the hepatic cytochrome oxidase system, which could lead to an aberration
      in porphyrin metabolism and subsequently cause porphyria. We report a case of PCT
      in an HIV-infected patient who had multiple risk factors for this disorder.

PMID- 15861868
TI  - Decreasing your risks of medication error when writing a prescription.

PMID- 15861869
TI  - Ex-ante economic analysis of animal disease surveillance.
AB  - This paper provides an ex-ante economic analysis comparing four alternative
      intervention strategies for the control and eradication of rinderpest against a
      scenario of no intervention in a cattle population similar in size to that of
      Ethiopia. The interventions were three different coverage levels of mass
      vaccination and one surveillance-based programme where vaccination targeted
      infected sub-populations. For each scenario, the disease impact was estimated
      using an open-population, state-transition SEIR ('susceptible', 'exposed',
      'infectious', 'recovered') disease transmission model with parameter estimates
      developed for lineage 1 rinderpest virus. Projected economic surplus gains and
      costs estimated from the rinderpest eradication programme in Ethiopia were
      analysed using benefit-cost methods. Social net present values (NPVs) and benefit
      cost ratios (BCRs) were calculated. Although the economic model found that BCRs
      were greater than one for all interventions examined, the scenarios of intensive
      mass vaccination (75% vaccination coverage) and surveillance with targeted
      vaccination were economically preferable. The BCRs for these strategies were 5.08
      and 3.68, respectively. Sensitivity analysis revealed that an increase in market
      prices for beef and milk increased the value of economic loss, the economic
      surplus and returns to investments in terms of NPVs and BCRs. An increase in
      demand and supply elasticities for beef and milk decreased the value of economic
      losses. This also had a negative effect on economic surplus and NPVs. The effect
      of an increase in the discount rate reduced returns to investments, with lower
      NPVs and BCRs. The authors note that 75% mass vaccination coverage was attempted
      in Ethiopia in the early 1990s, but failed to eradicate rinderpest because the
      approach was logistically too difficult to implement in practice. Subsequently,
      an effective surveillance and epidemiologically targeted vaccination programme
      was developed and has apparently resulted in the eradication of rinderpest from
      Ethiopia (the last case was recorded in 1996). The authors conclude that epidemio
      surveillance with targeted vaccination is both an economically viable and
      realistic strategy and offers benefits that extend beyond rinderpest eradication.

PMID- 15861870
TI  - A new method for assessing the impact of emerging infections on global trade.
AB  - In this paper, the authors describe a new method for assessing the impact of
      emerging infections on global trade flows. When one compares notifications to the
      World Trade Organization (WTO) of the emergency measures taken to control certain
      animal and plant diseases with the trade values of certain products from the
      United Nation's Commodity Trade Statistics Database (Comtrade) (identified
      through the World Customs Organization's harmonised system of tariff product
      codes [HS]), it is possible to estimate the extent to which trade has been
      diverted from the affected economies. The authors study in detail the example of
      bovine spongiform encephalopathy (BSE). When member countries of the WTO change
      their import policies towards the goods of a trading partner, as the result of an
      emerging disease such as BSE, they must file notifications of such changes
      through the Sanitary and Phytosanitary Committee of the WTO. To quantify the
      impact of BSE on trade, the authors compared these notifications against Comtrade
      statistics, using the HS 1996 tariff code variable. (The HS 1996 tariff codes
      allow the tracking and recording of the volumes of exports and imports, in
      quantity and value, between any two member countries between 1998 and 2000 in the
      database.) The authors then used this linked dataset to describe the dollar
      impact of the BSE-related notifications filed in 2000 on the trade flow of
      imports. The results of this study suggest that economies affected by BSE
      notifications saw a decline of US$5.6 billion from hypothetical projections in
      designated products. At the same time, unaffected economies saw an increase of
      US$1.5 billion from hypothetical projections in the same products. Thus, it may
      be concluded that import restrictions to control the spread of emergent
      spongiform encephalopathy infection had a significant effect on trade flows.
      These results also emphasise the interconnectedness of global trade: trade
      restrictions for some economies may enhance trade opportunities for others.
      Further studies using these methods are warranted.

PMID- 15861871
TI  - Predicting the risk of bluetongue through time: climate models of temporal
      patterns of outbreaks in Israel.
AB  - Determining the temporal relationship between climate and epidemics of Culicoides
      borne viral disease may allow control and surveillance measures to be implemented
      earlier and more efficiently. In Israel, outbreaks of bluetongue (BT) have
      occurred almost annually since at least 1950, with severe episodes occurring
      periodically. In this paper, the authors model a twenty-year time-series of BT
      outbreaks in relation to climate. Satellite-derived correlates of low
      temperatures and high moisture levels increased the number of outbreaks per year.
      This is the first study to find a temporal relationship between the risk of
      Culicoides-borne disease and satellite-derived climate variables. Climatic
      conditions in the year preceding a BT episode, between October and December,
      coincident with the seasonal peak of vector abundance and outbreak numbers,
      appeared to be more importantthan spring or early summer conditions in the same
      year as the episode. Since Israel is an arid country, higher-than-average
      moisture levels during this period may increase the availability of breeding
      sites and refuges for adult Culicoides imicola vectors, while cooler-than-average
      temperatures will increase fecundity, offspring size and survival through
      adulthood in winter, which, in turn, increases the size of the initial vector
      population the following year. The proportion of variance in the annual BT
      outbreak time-series resulting from climate factors was relatively low, at around
      20%. This was possibly due to temporal variation in other factors, such as viral
      incursions from surrounding countries and levels of herd immunity. Alternatively,
      since most BT virus (BTV) circulation in this region occurs silently, in
      resistant breeds of local sheep, the level of transmission is poorly correlated
      with outbreak notification so that strong relationships between BTV circulation
      and climate, if they exist, are obscured.

PMID- 15861872
TI  - [Newcastle disease in southern Chad: peak epidemic periods and the impact of
      vaccination].
AB  - In spite of its universally acknowledged importance, backyard chicken production
      is still being hampered by Newcastle disease in some parts of the world. In Chad,
      the disease has been reported almost everywhere in the country and confirmed in
      several regions, but there are no control measures in place. A survey was
      conducted at three sites in south-eastern Chad in July and August 2001, based on
      face-to-face interviews with 20% of the peasant farmers keeping chickens at these
      sites. The aim was to collect information on peak epidemic periods and on ways in
      which the infection spreads. The survey revealed that the peak epidemic periods
      for Newcastle disease are April, during the mango harvesting and selling period,
      and December, when trade increases for the seasonal festivities. The survey also
      showed that peasant farmers attach great importance to chicken farming. The
      survey was followed by a vaccination trial in November 2001 and February 2002,
      using the La Sota strain administered ocularly. All of the birds vaccinated
      during the trial were successfully protected from the disease and both chicken
      production and the income of the villagers increased. The authors conclude that
      in order to sustain poultry farming and maximise production in the southern zone,
      vaccination programmes must be urgently introduced, campaigns to raise awareness
      of Newcastle disease should be carried out and financial support to pay for
      vaccines should be provided. Efforts to combat other causes of poultry mortality
      must also be undertaken.

PMID- 15861873
TI  - An investigation into the source and spread of foot and mouth disease virus from
      a wildlife conservancy in Zimbabwe.
AB  - African buffalo were introduced into a wildlife conservancy in the southeast of
      Zimbabwe in an effortto increase the conservancy's economic viability, which is
      primarily based on eco-tourism. The buffalo were infected with SAT serotypes (SAT
      1, SAT-2 and SAT-3) of foot and mouth disease (FMD) virus, and in order to
      isolate the conservancy and prevent the transmission of FMD to adjacent
      populations of domestic livestock, the conservancy was surrounded by a double
      fence system, 1.8 m in height. The intention was to prevent the movement of both
      wildlife and domestic animals across the perimeter. However, two years after the
      buffalo were introduced, FMD occurred in cattle farmed just outside of the
      conservancy. Using serological and molecular diagnostic tests, epidemiological
      investigations showed that it was most likely that antelope (impala or kudu),
      infected through contact with the buffalo herd within the conservancy, had jumped
      over the fence and transmitted the virus to the cattle.

PMID- 15861874
TI  - [A study of the epidemiological behaviour of bovine paratuberculosis using time
      series in Tandil in the province of Buenos Aires, Argentina].
AB  - The authors present the results of a study conducted using time series data from
      the 1993--2001 period in order to characterise the clinical behaviour of bovine
      paratuberculosis. The case data, confirmed by macroscopic examination, enzyme
      linked immunosorbent assay (ELISA) and comparative tuberculin test, came from the
      herd health register, located in Tandil in the province of Buenos Aires,
      Argentina. The upper limit of customary variation was observed in April, with an
      incidence of 2.5%. In 1997, 1999, 2000 and 2001 the disease was epidemic and a
      peak of 5.6% occurred in March 1999. Over the long term a rise in the total
      annual incidence was observed, from 0.7% in 1993 to 10.2% in 2001. Knowledge
      about the epidemiology of paratuberculosis will help to control the disease and
      minimise its impact on the national economy, and will also provide new
      information for use in public health.

PMID- 15861875
TI  - Serological survey of selected pathogens of free-ranging foxes in southern
      Argentina, 1998--2001.
AB  - A serological survey was conducted in the Patagonia region of Argentina to
      estimate the prevalence of nine disease agents within the populations of free
      ranging culpeo (Dusicyon culpaeus) and grey (Dusicyon griseus) foxes. The disease
      agents were Aujeszky's disease virus (ADV), Brucella, canine adenovirus (CAV),
      canine distemper virus (CDV), canine parvovirus (CPV), Encephalitozoon cuniculi,
      Leptospira, Neospora caninum, and Toxoplasma gondii. A total of 84 foxes were
      sampled (28 culpeo and 56 grey), and 73% of the sera had antibodies against one
      or more pathogens. Among these seropositive sera, 47% of them reacted to only one
      antigen, while the other 53% reacted to multiple antigens. The presence of
      antibodies to Toxoplasma (20%), Neospora (44%), Leptospira (30%) and Brucella
      (18%) suggests that these organisms actively circulate in the area. Antibodies
      against CDV, CAV and CPV were detected in 2%, 5% and 5% of foxes, respectively.
      Regarding Encephalitozoon cuniculi and ADV, no evidence of either was found.

PMID- 15861876
TI  - Prevalence and distribution of peste des petits ruminants virus infection in
      small ruminants in India.
AB  - Peste des petits ruminants (PPR) is an acute febrile viral disease of goats and
      sheep characterised by mucopurulent nasal and ocular discharges, necrotising and
      erosive stomatitis, enteritis and pneumonia. The disease is endemic in India and
      causes large economic losses each year due to the high rates of mortality and
      morbidity in infected sheep and goats. The present study reports observations
      from 58 laboratory confirmed outbreaks of PPR and provides details of the
      prevalence of antibodies to PPR virus (PPRV) in 4,407 serum samples of small
      ruminants. Most of the clinical specimens used for the study originated from the
      northern and central parts of India. Serum samples used for the detection of
      antibodies to PPRV were derived from a greater number of regions within the
      country, however, these samples may not be a true representation of the target
      population (unvaccinated sheep and goats over 3 months old). Indigenously
      developed monoclonal antibody-based diagnostic kits were used for the detection
      of PPRV antigen (sandwich enzyme-linked immunosorbent assay [ELISA]) and antibody
      (competitive ELISA). Findings suggested that the disease outbreaks were more
      severe in goats than sheep and that the frequency of disease outbreaks was
      greater between the months of March and June (51.7%) as compared to other periods
      of the year. Based on the screening of the 4,407 sera samples, the antibody
      prevalence of PPRV in small ruminants in India was 33% (95% confidence interval:
      32.3% to 33.7%). The prevalence of antibodies to PPRV was noted to differ between
      species (i.e. sheep versus goats), age groups and geographical regions. A greater
      proportion of the sheep (36.3%) versus the goat (32.4%) population was infected
      with PPRV. The distribution and prevalence of antibodies to PPRV among various
      age groups of animals indicated that goats were exposed at an earlier age than
      the sheep, suggesting that goats may be more susceptible to infection with PPRV.
      A greater number of positive cases were observed in the southern and southwestern
      part of the country (30%-60%) as compared to northern India (10%-30%). These
      findings may be correlated with variations in the sheep and goat husbandry
      practices within different geographic regions, the topography of different states
      and the socio-economic status of individual Indian farmers.

PMID- 15861877
TI  - Seroprevalence of infectious bovine rhinotracheitis in mithun (Bos frontalis) in
      India.
AB  - A preliminary study on the seroprevalence of infectious bovine rhinotracheitis
      (IBR) in different strains of mithun maintained atthe National Research Centre on
      Mithun, Nagaland, India, revealed that the overall prevalence of IBR in these
      mithun was 19%. This paper examines the results of that preliminary study. To the
      knowledge of the authors, this is the first report on the seroprevalence of IBR
      in mithun in India. The highest prevalence of IBR was observed in mithun found in
      Arunachal Pradesh (38.46%), followed by those found in Mizoram (18.18%) and
      Nagaland (15.15%). None of the animals from Manipur were found to test positive
      for antibodies against IBR. The sex of the animal had no influence on IBR
      prevalence. The prevalence was found to be highest (27.03%) in mithun above three
      years of age and lowest (7.69%) in mithun aged between six months and one year.
      The prevalence of IBR was found to be 88.9% in breeding mithun bulls. In this
      paper, the authors briefly discuss the possible roles of feral fauna and domestic
      livestock in the transmission of this disease to mithun and vice versa. Various
      measures that may help in the prevention and control of IBR in mithun are also
      surveyed. However, it should be emphasised that this study is a preliminary one,
      and the authors are currently engaged in further research.

PMID- 15861878
TI  - Human and animal brucellosis in Jordan between 1996 and 1998: a study.
AB  - Between 1996 and 1998, a total of 2,494 samples of blood from humans and animals
      were collected and tested for brucellosis. This total included 1,594 samples of
      animal blood, collected from 1,050 sheep from 20 flocks, and 544 goats from eight
      herds. The serum samples were tested using the Rose Bengal test, the tube
      agglutination test, the complement fixation test and an enzyme-linked
      immunosorbent assay. Moreover, a complete history was compiled from each
      flock/herd. The rate of abortions in sheep due to brucellosis ranged from 0.5% to
      56%, with a mean of 33.2%. The goats had a higher abortion rate. Thirty-four
      aborted sheep foetuses collected from these 20 flocks were bacteriologically and
      pathologically examined. A pure culture of Brucella melitensis biotype 3 was
      isolated from 21 of the aborted foetuses. The human blood samples were collected
      from two groups: first, from 800 apparently healthy people who were reporting to
      community hospitals for routine health checks and secondly, from 100 people from
      groups with a high-risk of contracting brucellosis, such as veterinarians, sheep
      herders and laboratory technicians. The Brucella antibody titres for the 900
      human serum samples were obtained using the microtitre agglutination test. The
      cumulative percentage of the serum samples showing a titre reading greater than
      1:80 was higher in the at-risk group than among the normal population (7%
      compared to 4.1%). Although these results were not statistically significant, the
      higher percentage of positive reactors among the high-risk group may indicate an
      increased risk factor among professional agricultural and veterinary personnel in
      Jordan. It was concluded that brucellosis is common in sheep and goats in Jordan,
      subjecting the human population to high risks. Brucella melitensis Rev. 1
      vaccination has been internationally recognised as the key to successfully
      controlling the disease. All animals in Jordan were repeatedly vaccinated between
      1996 and 1998 on a trial basis, using a reduced dose of 1 x 10(5) colony-forming
      units (CFU). Cumulative data on the annual rate of human cases of brucellosis
      indicate that fewer people are affected each year. The same is true for the rate
      of abortions in animals. Such evidence strongly suggests that the vaccination
      programme has been successful. However, as wild strains of Brucella have also
      been isolated from vaccinated animals, the authors recommend increasing the
      amount of vaccine to a full dose of 1 to 2 x 10(9) CFU and vaccinating young
      female animals between the ages of three and eight months. To avoid brucellosis
      in humans, people should be educated about the dangers of contact with infected
      animals and the consumption of raw milk and milk products.

PMID- 15861879
TI  - [The current importance of veterinary public health: the SAPUVET project].
AB  - The authors propose reviewing the current needs for implementing veterinary
      public health programmes, from both the teaching and professional standpoints.
      This is warranted by the fact that veterinary public health has become extremely
      important in various fields of work, beyond conventional food inspection. The
      article discusses the public health role which veterinarians must play and the
      interactions between their activities and those of other groups such as doctors,
      epidemiologists, ecologists, chemists, or even sociologists and anthropologists.
      The authors also study and assess the basic working tool in veterinary public
      health--epidemiological surveillance--and how it operates on the basis of
      diagnosis and risk analysis. The second part of the article discusses the need to
      unify criteria for veterinary public health training and the role which the
      SAPUVET network is playing in doing so (SAPUVET is a European Union-supported
      project within the ALFA programme that is designed to establish links between
      Latin American and European veterinary faculties).

PMID- 15861880
TI  - The provision of animal health care to smallholders in Africa: an analytical
      approach.
AB  - Many of the problems associated with the delivery of quality veterinary services
      to smallholders in Africa are attributed to the complexity of the provision of
      animal health care (AHC) in sub-Saharan Africa. In this region, a holistic and
      analytical approach is needed to determine area-specific requirements for
      sustainable, and thus quality, AHC. This study examines three components of the
      animal health care system in sub-Saharan Africa, namely, the structure, the
      process and the outcomes. It focuses particularly on the factors that contribute
      to the quality of the structure and the process. For this purpose, two measures
      of quality are used, i.e. availability (in relation to the structure) and
      acceptability (in relation to the process). The authors identify factors that
      affect the availability and acceptability of AHC and suggest ways in which they,
      and hence the quality of AHC provided to smallholders in Africa, can be improved.

PMID- 15861881
TI  - Foot and mouth disease in Mali: the current situation and proposed control
      strategies.
AB  - Two main reasons prompted the authors to write this paper. First, outbreaks of
      foot and mouth disease (FMD) have occurred repeatedly in Mali and neighbouring
      countries during the last decade. Secondly, there is a pressing need for control
      strategies, since the first molecular epidemiological studies of FMD virus in
      West Africa have demonstrated that FMD transmission across national boundaries is
      common in this region. The authors discuss the FMD outbreaks that occurred during
      the period of 1980 to 1996, which were reported to the Central Livestock Office
      in Mali by field veterinarians. The outbreaks in 1980 and 1982 were confined to
      the regions of Kayes and Gao, respectively. Between 1991 and 1992, outbreaks
      occurred in Segou, Sikasso and Bamako. In 1996, FMD outbreaks were reported in
      cattle populations throughout Mali, except in Kidal in the Sahara desert, where
      temperatures reach 45 degrees C. High mortality was reported in young animals,
      while morbidity approached 100% in adult cattle.

PMID- 15861882
TI  - Use of web-enabled databases for complex animal health investigations.
AB  - Web-enabled databases developed in the late 1990s to help organise large web
      sites and allow data capture via browser-based forms. By enabling users outside a
      closed network access to a central database, they permit greater flexibility than
      traditional 'client-server' systems. Accordingly, web-enabled databases introduce
      a new tool for epidemiologists, permitting direct data capture at source and thus
      avoiding many of the delays and errors arising from paper forms and manual data
      entry. In addition, real-time data collection permits sophisticated decision
      support and reporting, and thus improved project co-ordination and participation.
      Nevertheless, the technology is complex and the development of a web-application
      requires an attention to information technology project management equal to that
      of the scientific trial or investigation. The potential and problems of web
      database applications are illustrated by a bespoke system ('PathMan') developed
      by the Veterinary Laboratories Agency of the United Kingdom Department for
      Environment, Food and Rural Affairs to manage a large multi-site study
      investigating the pathogenesis of bovine tuberculosis in England and Wales.

PMID- 15861883
TI  - [The design and development of a quality system for the diagnosis of exotic
      animal diseases at the National Centre for Animal and Plant Health in Cuba].
AB  - A quality system for the diagnosis of exotic animal diseases was developed at the
      national centre for animal and plant health (CENSA), responsible for coordinating
      the clinical, epizootiological and laboratory diagnosis of causal agents of
      exotic animal diseases in Cuba. A model was designed on the basis of standard ISO
      9001:2000 of the International Organization for Standardization (ISO), standard
      ISO/IEC 17025:1999 of ISO and the International Electrotechnical Commission,
      recommendations of the World Organisation for Animal Health (OIE) and other
      regulatory documents from international and national organisations that deal
      specifically with the treatment of emerging diseases. Twenty-nine standardised
      operating procedures were developed, plus 13 registers and a checklist to
      facilitate the evaluation of the system. The effectiveness of the quality system
      was confirmed in the differential diagnosis of classical swine fever at an animal
      virology laboratory in Cuba.

PMID- 15861884
TI  - Quality management in reference tests for the diagnosis of classical swine fever.
AB  - Inter-laboratory comparison tests for the diagnosis of classical swine fever
      (CSF) have been established by the national swine fever laboratories of European
      Union (EU) Member States. They provide a method of measuring both the quality of
      the results of diagnostic tests performed by laboratories and the competence with
      which they were performed. The objective is that all laboratories obtain the same
      result when investigating the same sample. This study evaluates the results of
      serological and virological reference tests for CSF (neutralisation test and
      virus isolation) performed over a period of three years. The sensitivity of the
      serological diagnosis for the detection of CSF antibodies was very good and
      revealed a tolerance limit of the scored antibody titres of one dilution step.
      Results on the same sample in two consecutive years were similar. The variation
      of the scored antibody titres was larger when testing sera with a low CSF
      antibody titre. The interpretation of the antibody titres as 'CSF positive or
      negative' was only slightly altered by these variations. The backtitration of a
      neutralisation test (used as a control measure) is a more mathematical value
      which does not correlate directly with the biological system. Commercial CSF
      antibody enzyme-linked immunosorbent assays still display a lower sensitivity on
      individual samples compared to the reference neutralisation test. Classical swine
      fever virus isolation was well established in all participating laboratories and
      caused very few problems. Specificity of CSF diagnosis by investigating CSF
      antibody and CSF virus negative sera was not problematic either. In general, the
      reference tests for CSF diagnosis are well established in the EU. They are based
      on living systems, e.g. cells and virus, and consequently they have a different
      tolerance limit than pure mathematical values. What is important is that the
      interpretation of the test result is identical in all laboratories.

PMID- 15861885
TI  - Salmonella isolates from wild birds and mammals in the Basque Country (Spain).
AB  - The authors investigated the prevalence of Salmonella spp. in 205 wild birds and
      mammals belonging to 45 species during the years 2001 and 2002 in the Basque
      Country (Spain). Salmonella was isolated from 16 (7.8%) animals. The prevalence
      was 8.5% (7/82) in birds, and 7.2% (9/123) in mammals. Nine serotypes, all of
      them belonging to the species Salmonella enterica, were identified: two isolates
      of Typhimurium (from 1/3 griffon vultures [Gyps fulvus], and 1/5 sparrowhawks
      [Accipiter nisus]); one of 6,14:z4, z23: (subsp. houtenae, 1/1 common kestrel
      [Falco tinnunculus]); one of Muenchen (1/1 captive Harris's hawk [Parabuteo
      unicinctus]); two of Enteritidis (1/5 tawny owls [Strix aluco], and 1/14 foxes
      [Vulpes vulpes]); one of Give, Newport and Umbilo and one untyped islolate (4/22
      badgers [Meles meles]); two of Worthington and one of 38:IV:z35 (subsp. arizonae,
      3/40 wild boars [Sus scrofa]); and three other untyped isolates (1/1 northern
      fulmar [Fulmarus glacialis], 1/11 buzzards [Buteo buteo], 1/4 genets [Genetta
      genetta]). Salmonella isolation was never associated with macroscopic or
      microscopic lesions. The results of this study confirm the importance of wildlife
      as a Salmonella reservoir and as a potential risk for humans and livestock.

PMID- 15861886
TI  - Abortions, stillbirths and deformities in sheep at the Al-Ahsa oasis in eastern
      Saudi Arabia: isolation of a bluetongue serogroup virus from the affected lambs.
AB  - A wave of abortions, stillbirths and deformities in sheep occurred at the Al-Ahsa
      oasis in the eastern region of Saudi Arabia in the second half of 1999. The
      abortions were recorded in August and September and stillbirths and deformities
      in neonates were observed in October. Adult sheep were clinically normal. A virus
      was isolated in chicken embryos, adapted to Vero cell culture and further
      identified as bluetongue (BT) virus. The virus isolated was not neutralised by
      the Akabane virus. Reference hyperimmune serum against antibodies to BT virus
      detected in the sera of the dams gave positive results for BT but negative
      results for both Akabane and bovine viral diarrhoea virus. It was concluded that
      the outbreak was caused by a virus of the BT serogroup. The authors present the
      clinico-pathological and epidemiological situation of the disease outbreak.

PMID- 15861887
TI  - An epizootic of equine influenza in Upper Egypt in 2000.
AB  - This study describes an epizootic of respiratory tract disease caused by
      influenza virus infection in a large population of equines in Luxor and Aswan,
      Upper Egypt, during the winter of 2000. The epizootic started in January and the
      infection rate reached its peak in February before gradually decreasing until the
      end of April, 2000. Horses, donkeys and mules of all ages and both sexes were
      affected. Free movement of the infected equines and direct contact between the
      animals at markets facilitated the rapid spread of the disease. The cause of the
      epizootic was established by use of serological testing and the identification of
      the influenza virus in nasal secretions. Egg inoculation and the
      haemagglutination test were used to detect the influenza virus. Both
      haemagglutination inhibition (HI) and agar gel precipitation tests were performed
      to identify the isolated influenza virus using reference antisera against A/Equi
      1 (H7N7) and A/Equi-2 (H3N8). Antibodies against the equine influenza virus were
      demonstrated in 416 (95.6%) out of 435 collected sera using the HI test. High
      rectal temperature, inappetence, conjunctivitis, redness of nasal mucosa, a
      serous to mucopurulent nasal discharge and a harsh dry cough were the most common
      clinical manifestations. Stress factors, such as using equines for heavy
      transportation and drawing, precipitated the onset of the disease, intensified
      the clinical syndrome, delayed recovery and facilitated secondary bacterial
      infection. The present study suggested that the absence of a vaccination
      programme against equine influenza was one of the principal causes of the spread
      of infection during this outbreak. In conclusion, the implementation of a
      national equine influenza vaccination programme, using an effective updated
      vaccine, is essential in Egypt.

PMID- 15861888
TI  - Determination of bovine rotavirus G genotypes in Kashmir, India.
AB  - Rotavirus ribonucleic acid (RNA) was extracted from ten faecal samples of
      diarrhoeic calves positive for group A rotavirus by enzyme-linked immunosorbent
      assay (ELISA). A portion of the extracted RNA was run in polyacrylamide gel to
      determine the presence of rotaviral RNA and the rest subjected to reverse
      transcriptase-polymerase chain reaction (RT-PCR) to generate the near full length
      VP7 gene. Only six samples yielded the desired product. The amplified products
      were subjected to G-typing by PCR using a cocktail of G6, G8 and G10 typing
      primers. All of the six samples were characterised as G10 and none of the samples
      revealed mixed infection by twin G types. Four samples, despite possessing
      sufficient rotavirus particles as revealed by ELISA and polyacrylamide gel
      electrophoresis, did not yield any amplified product on RT-PCR. This could be due
      to non-specific inhibitors of the PCR reaction, present in the faecal samples,
      being carried through the extraction procedures.

PMID- 15861889
TI  - A study of nasal and visceral schistosomosis in cattle slaughtered at an abattoir
      in Bangalore, South India.
AB  - The authors studied the incidence of nasal and visceral schistosomosis in 300
      male cattle that were slaughtered in 2001 at the Karnataka Meat and Poultry
      Marketing Corporation Limited abattoir in Bangalore, South India. The nasal and
      intestinal scrapings and their contents were screened for eggs and the nasal and
      visceral cuttings were examined for worms. Eggs of Schistosoma nasale and S.
      spindale were observed in 197 and 151 samples and worms in 218 and 204 carcasses
      respectively. A mild infection of S. nasale was observed in 129 animals and a
      mild infection of S. spindale in 124 animals, a moderate infection of S. nasale
      was found in 77 animals and a moderate infection of S. spindale in six animals.
      Twelve animals were heavily infected with S. nasale and 14 cattle were heavily
      infected with S. spindale. Mixed infections of both species occurred in 163
      animals. The level of infection was determined by the eggs per gram method and
      was found to be in the range of 1 to 310 eggs per gram for S. nasale and 1 to 201
      for S. spindale, this was a higher result than the eggs per cubic centimetre
      method, which indicated lower egg counts. Worms were recovered from 218 nasal and
      204 visceral cuttings. It was concluded that the incidence of nasal and visceral
      schistosomosis in cattle in this region is under-diagnosed and the carrier status
      of these animals in the subclinical state is potentially high.

PMID- 15861890
TI  - An outbreak of sheep pox on a sheep breeding farm in Jammu, India.
AB  - An outbreak of sheep pox occurred in December 2001 on a sheep breeding farm in
      Jammu, India. The farm maintains three exotic breeds of sheep, i.e. American
      Merino, Rambouillet and Australian cross. The disease agent was confirmed as
      sheep pox virus by clinical and post-mortem examination as well as laboratory
      testing. Typical pock lesions were dispersed over the body of the affected
      animals with nodular lesions observed in the lung tissue of the dead animals.
      Sheep pox virus antigen and antibody were detected in infected tissue and
      convalescent sera, respectively, with serological tests. Viral deoxyribonucleic
      acid was extracted from the infected tissue and amplified using a diagnostic
      polymerase chain reaction. Sheep of the Rambouillet breed were found to be most
      susceptible to infection with morbidity and mortality rates of 26.9% and 8.3%,
      respectively. Morbidity and mortality rates in the entire flock were 18.4% and
      6.3%, respectively. The grazing and migration pattern indicates that the disease
      was probably introduced to the farm by local sheep.

PMID- 15861891
TI  - Anthrax in Wabessa village in the Dessie Zuria district of Ethiopia.
AB  - In 2002 an investigation of sudden death in a goat in Wabessa village in the
      Dessie Zuria district of Ethiopia was undertaken using fresh blood brought to the
      Kombolcha Regional Veterinary Laboratory. The sample was examined using standard
      bacteriological techniques and animal pathogenicity tests were also performed.
      The laboratory investigation revealed Bacillus anthracis as the cause of sudden
      death. Information gathered from stockowners in the same village revealed other
      similar recent cases and deaths, both in animals and humans, with farmers clearly
      describing the clinical signs and necropsy findings of anthrax. The disease
      occurs annually in this area in May and June, and in the 2002 outbreak mortality
      rates of 7.7%, 32.7% and 47.1% were observed in cattle, goats and donkeys,
      respectively. This study indicates that the community of this particular village
      neither knows of, nor practises, any of the conventional methods for anthrax
      control. The cutaneous form of the disease in humans and the environmental
      contamination associated with the practise of opening cadavers are briefly
      described and the findings are discussed with reference to the epidemiology of
      anthrax in both Ethiopia and elsewhere. Control strategies are also recommended.

PMID- 15861892
TI  - Tuberculous lesions not detected by routine abattoir inspection: the experience
      of the Hossana municipal abattoir, southern Ethiopia.
AB  - The efficacy of the meat inspection procedures implemented for the detection of
      tuberculous cattle was evaluated by testing for bovine tuberculosis in 751
      animals. The study involved routine inspection at slaughter, collection of
      tissues for detailed examination in the laboratory, and bacteriological
      investigation to identify Mycobacterium bovis. Of the 751 carcasses examined, 34
      (4.5%) were found to have tuberculous lesions. Routine abattoir inspection
      detected only 29.4% of the carcasses with visible lesions. Eighty-four percent of
      the tuberculous lesions were found in the lungs and thoracic lymph nodes, 11.5%
      in the lymph nodes of the head, and the remaining 4.5% in the mesenteric and
      other lymph nodes of the carcasses. In addition, M. bovis was isolated from a
      carcass that presented no gross tuberculosis lesions. The low sensitivity of
      routine abattoir inspection demonstrates that existing necropsy procedures should
      be improved.

PMID- 15861893
TI  - An investigation into natural resistance to African swine fever in domestic pigs
      from an endemic area in southern Africa.
AB  - A population of domestic pigs in northern Mozambique with increased resistance to
      the pathogenic effects of African swine fever (ASF) virus was identified by the
      high prevalence of circulating antibodies to ASF virus. An attempt was made to
      establish whether the resistance in this population was heritable. Some of these
      pigs were acquired and transported to a quarantine facility and allowed to breed
      naturally. Offspring of the resistant pigs were transferred to a high security
      facility where they were challenged with two ASF viruses, one of which was
      isolated from one of the Mozambican pigs and the other a genetically closely
      related virus from Madagascar. All but one of the 105 offspring challenged
      developed acute ASF and died. It therefore appears that the resistance
      demonstrated by these pigs is not inherited by their offspring, or could not be
      expressed under the conditions of the experiment. The question remains therefore
      as to the mechanism whereby pigs in the population from which the experimental
      pigs were derived co-existed with virulent ASF viruses.

PMID- 15861894
TI  - Comparison of serological tests for the detection of ovine and caprine antibody
      to Brucella melitensis.
AB  - The indirect enzyme-linked immunosorbent assay (IELISA), the competitive enzyme
      linked immunosorbent assay (CELISA) and the fluorescence polarisation assay (FPA)
      were evaluated with sera from sheep experimentally infected with Brucella
      melitensis and negative Canadian sheep. The sensitivity and specificity of the
      assays were as follows: IELISA: 91.7% and 97.6%, CELISA: 75.0% and 99.8% and FPA:
      91.7% and 89.5%. Sera from the same experimental population were divided
      according to serological reaction in the rose bengal agglutination test (RBT) and
      the complement fixation test (CFT). Reactivity relative to the RBT positive and
      CFT positive sera were as follows: IELISA: 99.7%, CELISA: 93.2% and FPA: 99.1%.
      Since sera from goats with proven B. melitensis infection were not available, 699
      sera from goats judged positive in the buffered antigen plate agglutination test
      (BPAT) and CFT and 982 BPAT/CFT negative Canadian goats were used. The
      sensitivity and specificity of the assays relative to the BPAT and CFT positive
      sera were: IELISA: 99.4% and 98.0%, CELISA: 95.4% and 97.1% and FPA: 92.7% and
      99.8%.

PMID- 15861895
TI  - Serological diagnosis of bovine brucellosis: a review of test performance and
      cost comparison.
AB  - The authors reviewed over 50 publications in which the sensitivity and
      specificity values of assays used for the detection of exposure to Brucella
      abortus had been examined. The sum of the sensitivity and specificity values for
      each test was averaged to give a performance index (PI) and allow for a
      comparison between the different methodologies. A score of 200 was perfect. Based
      on the PI, the buffered antigen plate agglutination test (BPAT) rated highest (PI
      = 193.1) among the conventional tests. This indicates better accuracy than the
      other conventional tests including the Rose Bengal test (PI = 167.6) and the
      complement fixation test (PI = 172.5). Overall, the primary binding assays,
      including the fluorescence polarisation assay (PI = 196.4), the indirect enzyme
      linked immunosorbent assay (PI = 189.8) and the competitive enzyme-linked
      immunosorbent assay (PI = 188.2), were more accurate than the conventional tests,
      except for the BPAT. In addition, a fee comparison suggested that the primary
      binding tests were price competitive with conventional tests for the diagnosis of
      brucellosis and, therefore, had a better combined cost/efficiency rating.

PMID- 15861896
TI  - Enhanced laboratory diagnosis of foot and mouth disease by real-time polymerase
      chain reaction.
AB  - The performance of an automated real-time reverse transcription polymerase chain
      reaction (RT-PCR) was compared to virus isolation (VI) in cell culture and
      antigen detection enzyme-linked immunosorbent assay (ELISA) for the laboratory
      diagnosis of foot and mouth disease (FMD). The World Reference Laboratory for FMD
      in Woking, the United Kingdom, examined a collection of 334 epithelia received
      from eighteen countries between August 2002 and January 2004. The results showed
      that all VI positive (n = 195) and VI and ELISA positive samples combined (n =
      204) were also positive by RT-PCR. Depending on the cut-off used, FMD virus
      genome was detected in a minimum of an additional 60 samples (18% of all samples
      tested). Furthermore, the RT-PCR generated results in less than one day from test
      commencement in contrast to up to 4 days to define some positive and all negative
      samples by VI. The study demonstrates that real-time RT-PCR provides an extremely
      sensitive and rapid procedure for improved laboratory diagnosis of FMD.

PMID- 15861897
TI  - Antibacterial activity of bee honey and its therapeutic usefulness against
      Escherichia coli O157:H7 and Salmonella typhimurium infection.
AB  - The authors studied the effect of storage period and heat on the physical and
      chemical properties of honey and proceeded to study the antibacterial effect of
      honey on Escherichia coli and Salmonella typhimurium. In samples of honey
      (Egyptian clover honey) that were heat-treated and stored over a long period of
      time, water content decreased, hydroxymethyl furfural (HMF) was produced and
      increased in concentration, and enzyme activity decreased. Colour, measured in
      optical density, was markedly affected in honey samples stored over long periods
      of time, as was the refractive index, but electrical conductivity remained
      unaffected by storage or heating. Similarly, the storage period had no effect on
      pH value. To study the therapeutic effect of honey on E.coli and S. typhimurium,
      25 isolates of E. coil O157:H7 (18.5%) and 49 isolates of S. typhimurium (36.2%)
      were isolated from 135 samples taken from children and calves (30 stool samples
      from children and 105 samples from calf organs and faecal swabs). Most E. coli
      O157:H7 and S. typhimurium isolates were highly resistant to most antibiotic
      discs. In vitro, the antibacterial effect of honey was more pronounced on E. coil
      O157:H7 than on S. typhimurium. Water content, pH value, HMF and the presence of
      H2O, all played an important role in the potency of olover honey as an
      antibacterial agent. In vivo, mice were used as a model for studying the
      parenteral usefulness of honey as an antibacterial agent against both pathogens.
      The antibacterial activity of honey that had been stored over a long period of
      time decreased and high concentrations of honey proved more effective as
      antibacterial agents. In this study there was lower mortality among mice treated
      with honey but the parenteral application of honey and its therapeutic properties
      require further investigation.

PMID- 15861898
TI  - [The Spanish translation of the Manual of Diagnostic Tests and Vaccines for
      Terrestrial Animals: current and future solutions].
AB  - This article presents some of the problems that arose when preparing the Spanish
      translation of the Manual of Diagnostic Tests and Vaccines for Terrestrial
      Animals of the World Organisation for Animal Health (OIE). It contains a list of
      the language and translation problems encountered and the solutions that were
      found, some of which are only provisional. The problems are in part due to the
      lack of a multi-lingual terminological database approved by the OIE. The need for
      such a database, as well as for the harmonisation of veterinary terminology by
      the OIE Steering Committee and the Ad hoc Group on language policy, is discussed.

PMID- 15861899
TI  - Ostrich nutrition: a review from a Zimbabwean perspective.
AB  - The ostrich is an important animal in many livestock industries and, in the
      developing world, the export of meat and skins is a valuable source of foreign
      currency. As the successful growth and reproductive performance of ostriches
      depends on good nutrition it is extremely important to provide the correct diet.
      Some researchers have incorrectly assumed that poultry diets are useful for
      ostriches, but the vitamin and mineral requirements of these birds are unique and
      their diets should never be substituted with poultry or other livestock feeds.
      Producers should be knowledgeable about how different ingredients provide the
      essential nutrients for growth and development. Adequate nutrition is key to good
      flock performance and more research into ostrich nutrition is required. In
      Zimbabwe, one of the greatest costs involved in the keep of ostrich breeder birds
      is purchased feed, which can cost approximately US$ 4,555 for every 10 birds per
      annum. In order to cover these costs, the producer needs to ensure an adequate
      supply of birds for slaughter.

PMID- 15861900
TI  - Epidemiology of heart failure in primary care in Madeira: the EPICA-RAM study.
AB  - Chronic heart failure (CHF) is a serious public health problem all over the
      world. CHF has a high prevalence, affecting mainly the elderly, and causes severe
      disability and social and economic costs. AIM: To estimate the prevalence of
      chronic heart failure in the Autonomous Region of Madeira in 2001. METHODS: This
      was a community-based epidemiological survey involving subjects attending primary
      care centers selected by a combined two-stage sampling and stratifying procedure.
      General practitioners (GPs) randomly selected in proportion to the population of
      each municipality evaluated subjects aged over 25 years attending primary care
      centers, recruited consecutively and stratified by age. CHF cases were identified
      according to the Guidelines of the European Society of Cardiology for CHF
      diagnosis. RESULTS: Six hundred and eighty-six eligible subjects were evaluated
      by 30 GPs; 60 patients with CHF were identified. The overall prevalence and 95 %
      CI of CHF in Madeira was 4.69 % (2.91 % to 6.46 %), 3.53 % in males (0.81 % to
      6.26 %), and 5.58 % in females (3.37 % to 7.79 %). CHF prevalence increases with
      age: 1.24 % (0.00 % to 2.96 %) in the 25 to 49-year-old group, 6.17% (1.31 to
      11.03 %) in those aged 50 to 59 years, 7.62 % (0.75 to 14.49 %) in those aged 60
      to 69 years, 13.32 % (7.99 % to 14.49 %) in the 70 to 79-year-old group, and
      14.34 % in the group over 80 years old (7.59 % to 21.09 %). The prevalence of CHF
      due to systolic dysfunction was 0.76 % and 2.74 % with normal systolic function.
      CONCLUSIONS: The overall prevalence of CHF in Madeira was similar to that of
      mainland Portugal, and slightly higher than that of other European studies.
      Overall CHF prevalence increases sharply with age. The prevalence of CHF with
      preserved systolic ventricular function was similar to that reported by other
      recent European studies. The prevalence of CHF due to systolic dysfunction was
      much lower. The differences found may correspond to differences in methodology
      rather than actual differences in the population. CHF with left ventricular
      systolic dysfunction seems to be rare in primary care in Madeira. This may be
      related to the different public health organization in Madeira, and deserves
      further evaluation.

PMID- 15861901
TI  - Differences in outcome in primary angioplasty in women.
AB  - BACKGROUND: In acute myocardial infarction (AMI), primary percutaneous
      transluminal coronary angioplasty (PTCA) has proved to be the best therapeutic
      approach. Several factors have been associated with worse outcome in AMI in
      females. Are there differences in outcome in women undergoing PTCA for AMI? AIM:
      To evaluate gender influence on clinical outcome and in-hospital mortality in
      patients with AMI who undergo primary percutaneous interventions. METHODS: We
      studied 245 consecutive patients (72 women, 29.4 %), who underwent primary PTCA
      between January 2000 and December 2001. The following parameters were analyzed:
      risk factors for coronary artery disease including hypertension, diabetes,
      smoking, hypercholesterolemia and family history, previous AMI, PTCA or angina,
      pain-to-balloon time, extent of coronary disease and outcome. RESULTS: Female
      patients were older (67.9+/-11.6 vs. 59.6+/-13; p < 0.001) with a higher
      prevalence of hypertension (65.3 % vs. 47.4 %; p < 0.05) and angina (29.0 % vs.
      16.0 %; p < 0.05) and lower prevalence of smoking (27.8 % vs. 54.3 %; p < 0.001).
      Pain-to-balloon time was longer in women (6.8+/-4.1 vs. 5.4+/-3.7 hours; p <
      0.05). Extent of coronary disease was similar in both groups. Glycoprotein
      IIb/IIIa inhibitors were used in 84.7 % of women and 90.8 % of men. The frequency
      of hemorrhagic complications (5.6 % vs. 5.2 %) and arrhythmias (15.3 % vs. 10.4%)
      and in-hospital mortality (9.7 6.4 %) were higher in females, although without
      statistical significance (p = NS). Hospitalization time was similar in both
      groups. CONCLUSIONS: Despite the growing awareness of a gender bias in
      therapeutic approaches to AMI, there are still some differences in outcome, with
      a trend towards higher mortality rates in women. Older age and longer pain-to
      balloon time could account for this.

PMID- 15861903
TI  - Benefits and limitations of primary angioplasty in the elderly.

PMID- 15861902
TI  - Primary coronary angioplasty in the elderly.
AB  - BACKGROUND: Primary coronary angioplasty is the best therapeutic approach in
      acute myocardial infarction (AMI), and more so in the population aged over 75
      years, in whom the hemorrhagic risk of thrombolysis becomes almost unacceptable.
      AIM: To evaluate age-related influences on clinical evolution and in-hospital
      mortality in patients with AMI who undergo primary percutaneous coronary
      interventions (PCI). METHODS: We studied 245 consecutive patients (aged between
      31 and 90, 63+/-13), who underwent primary PCI between January 2000 and December
      2001. Forty-six patients (18.8%) aged over 75 years were compared with the rest.
      The following parameters were analyzed: risk factors for coronary artery disease
      including hypertension, diabetes, smoking, hypercholesterolemia and family
      history, previous AMI, PCI or angina, extent of coronary disease, angiographic
      results and in-hospital mortality. RESULTS: Female gender was more frequent in
      older patients (56.5% vs. 23.1%; p<0.001) and smoking was more prevalent in the
      younger group (54.3% vs. 13.0%; p<0.001), as was previous AMI (p<0.05). PCI
      success was high in both groups (93.5% in the older population and 96.7% in the
      rest; p=NS), multivessel coronary disease was significantly more frequent in the
      elderly group (41.3% vs. 26.2%; p<0.05), and glycoprotein IIb/IIIa inhibitors
      were used less (80.4% vs. 91%; p<0.05). Killip class evolution was more favorable
      in the younger group (class I in 88.4% vs. 69.8% in older patients; p<0.001). The
      number of hemorrhagic complications and in-hospital mortality were higher in
      elderly patients (3.5% vs. 13.0%; p<0.05 and 4.5% vs. 19.6%; p<0.001,
      respectively). CONCLUSIONS: Primary PCI has a similarly high success rate in
      elderly patients, although this age-group still has higher mortality. The
      increased rate of hemorrhagic complications in this population should lead to
      greater caution in the use of adjuvant antithrombotic drugs.

PMID- 15861904
TI  - Impact of a structured intensive follow-up program on the control of hypertension
      in coronary patients--a randomized trial.
AB  - INTRODUCTION: Hypertension is an important risk factor for cardiovascular events.
      Although several anti-hypertensive agents have shown to be effective in the
      treatment of hypertension, adequate blood pressure control is not frequent in
      most populations. The aim of this study was to evaluate the effect of a
      structured intensive follow-up program (SIFUP) on the control of blood pressure
      in coronary patients. PATIENTS AND METHODS: we performed a prospective,
      randomized study including 237 patients admitted to the Cardiology Department for
      acute coronary syndrome. Patients were randomly assigned to a SIFUP (n=129) or to
      the general cardiology outpatient department (COD) (n=108). An experienced doctor
      performed a blind assessment of blood pressure in 157 randomised patients, 9 to
      18 months after discharge. In statistical analysis, the chi-square test was used
      to compare proportions and the Student's t test to compare means. RESULTS: Both
      groups were predominantly male and mean age was similar. The proportion of
      patients with known hypertension randomised to the SIFUP and the COD did not
      differ. At the 9 to 18-month assessment there was no statistical significant
      difference in the proportion of patients with blood pressure under target values
      (57.5% in SIFUP and 48.5% in COD, p=NS). However, in hypertensive patients, the
      proportion of controlled patients was significantly higher in the SIFUP than in
      the COD (44.8% vs. 24.2%, p=0.05) and systolic and mean blood pressure were
      significantly lower in the SIFUP (respectively 139.0 vs. 148.8 mmHg, p=0.04 and
      98.7 vs. 103.9 mmHg, p=0.03); diastolic blood pressure was also lower in SIFUP
      (78.5 vs. 81.5 mmHg, p=NS). CONCLUSIONS: The SIFUP has shown to be effective in
      lowering blood pressure in hypertensive coronary patients. The proportion of
      patients with controlled blood pressure was consistently higher in the SIFUP.

PMID- 15861905
TI  - New diagnostic criteria for acute myocardial infarction and in-hospital
      mortality.
AB  - BACKGROUND: The recent introduction of new diagnostic criteria for acute
      myocardial infarction (AMI), with troponin measurement, has increased the number
      of patients admitted with this diagnosis. OBJECTIVE: To evaluate the
      epidemiologic and prognostic implications of the new diagnostic criteria for AMI.
      METHODS: This was a retrospective study of 586 patients admitted for acute
      coronary syndrome (ACS) to the coronary care unit of our hospital, between 2002
      and 2003. Data were collected from RECIMA, the Madeira Ischemic Heart Disease
      Registry. The population was analyzed following two different definitions of ACS:
      1 - old criteria (Group I): AMI with ST elevation (typical symptoms or ECG with
      ST-segment elevation and raised CK-MB >2x), AMI without ST elevation (typical
      symptoms or ECG without ST elevation and raised CK-MB >2x) and unstable angina
      (UA) (symptoms or ECG indicative of ischemia, with normal CK-MB, regardless of
      troponin status); 2 - new criteria (Group II): AMI with ST elevation (typical
      symptoms or ECG with segment ST elevation and raised CK-MB >2x or troponin), AMI
      without ST elevation (typical symptoms or ECG without ST-segment elevation and
      raised CK-MB >2x or troponin) and UA (symptoms or ECG indicative of ischemia,
      with normal enzymes). We evaluated whether this change in criteria had any
      influence on in-hospital mortality. RESULTS: The new criteria significantly (by
      11.9 %) increased the total number of patients admitted with AMI. This was due to
      an increase in AMI without ST elevation (p < 0.001) and a decrease in patients
      with UA (p < 0.001), with no changes in AMI with ST elevation. In-hospital
      mortality was lower in patients with AMI diagnosed by the new criteria and in
      those with UA. CONCLUSION: The overall increase in AMI resulting from the new
      diagnostic classification was accompanied by a decrease, although not
      statistically significant, of in-hospital mortality, probably due to the lower
      risk of the population analyzed.

PMID- 15861906
TI  - Circadian heart rate and blood pressure variability in autonomic failure.
AB  - Autonomic failure (AF) induces disabling orthostatic symptoms. Short-term heart
      rate (HR) and blood pressure (BP) orthostatic patterns are well characterized in
      these patients but data on long-term blood pressure and heart rate monitoring is
      lacking. The aim of this study was to assess circadian HR and BP variation in AF
      patients. We studied 8 patients with severe AF (7 with TTRmet30+ familial
      amyloidotic polyneuropathy and 1 with pure autonomic fairure)--Group A, and 2
      control groups (8 asymptomatic TTRmet30+ patients--Group B, and 16 normal aged
      matched controls--Group C). All groups underwent 24h HR and BP monitoring. Twenty
      four-hour systolic (SBP) and diastolic BP (DBP) were similar in all groups
      (114.5+/-10.6 and 73.2+/-6.7; 123.0+/-6.2 and 79.0+/-9.5; 118.6+/-10.1 and 71.4+/
      9.4 mmHg for groups A, B and C respectively). BP dipping was attenuated or even
      inverted (p < 0.01) in AF patients (SBP and DBP differences between day and
      night: -1.6+/-11.6 and 3.3+/-6.3; 10.0+/-1.0 and 11.7+/-1.5; 15.6+/-7.9 and
      16.2+/-5.8 mmHg for groups A, B and C respectively; p < 0.01). Although mean 24h
      HR was similar between patients and controls (80.9+/-14.0, 87.0+/-4.6 and 80.7+/
      5.2 bpm for groups A, B and C respectively), there were striking differences in
      heart rate variability between groups (max-min 24h HR difference: 46+/-16, 89+/
      11 and 91+/-9 bpm; pNN50: 0+/-0, 6+/-2 and 12+/-6%; SDRR 68+/-24, 128+/-10 and
      148+/-32 ms for groups A, BB and C; p < 0.01). There were significant differences
      between normal controls and asymptomatic TTRmet30+ controls in mean HR, diastolic
      blood pressure dipping and pNN50; p < 0.05. Autonomic failure can be suspected by
      simple 24h blood pressure evaluation and heart rate monitoring. Asymptomatic
      TTRmet30+ patients may already show some degree of autonomic impairment,
      particularly early vagal dysfunction.

PMID- 15861907
TI  - Coronary-subclavian steal syndrome. A case report.
AB  - Coronary-subclavian steal is an unusual clinical syndrome after successful
      internal mammary-coronary artery bypass grafting. Proximal subclavian artery (SA)
      stenosis is present and atherosclerotic disease is the underlying
      pathophysiologic mechanism in the majority of cases. The authors report a case of
      a sixty-two-year old man with angina and ventricular fibrillation soon after
      myocardial revascularization with left internal mammary artery (LIMA) to left
      anterior descending coronary (LAD). Dobutamine stress echocardiography showed
      ischemia in the anterior myocardial territory with patent LIMA-LAD bypass in the
      angiographic evaluation. This procedure showed occlusion of the proximal SA with
      reversal of flow in the LIMA. The best therapeutic approach was discussed and a
      carotid-subclavian bypass was performed with restoration of antegrade blood flow
      and reversal of the clinical setting.

PMID- 15861908
TI  - Psychosocial risk factors in coronary heart disease: beyond type A behavior.
AB  - OBJECTIVES: From a broad perspective of psychocardiology, our aim is to give an
      overview of the role that psychosocial risk factors play in coronary artery
      disease. METHODS: A review of the literature was made based on a systematic
      search of four databases: EBSCO, Proquest Psychology, Proquest Health and PubMed.
      In sample 1, two dependent (Coronary and Myocardial) and six independent
      variables (Type A, hostility, anger, depression, anxiety and psychosocial) were
      created. In sample 2, we searched directly for three descriptors (Type D
      personality, time urgency and coronary-prone behavior). Following this search,
      two sets of concepts were distinguished: (1) those relating to traditional
      research areas, and their critics, and (2) those included in the most recent
      trends, and their limitations. CONCLUSIONS: Research in psychocardiology has gone
      beyond the traditional concept of type A behavior pattern. The idea of a specific
      toxic component has been abandoned, in favor of a more holistic approach. The
      deleterious effects that negative emotions, particularly depression, as well as
      personality and socioeconomic status, may have on the functioning of various
      organs and psychosocial performance have now been recognized.

PMID- 15861909
TI  - Asymptomatic carotid bruit.
AB  - Cerebrovascular events are responsible for high morbidity and mortality, and
      carotid atherosclerosis with vascular stenosis is a major etiological factor in
      cerebrovascular disease. Carotid bruit is an important marker of generalized
      atherosclerosis. On the basis of good quality studies, we can conclude that it
      indicates an increased risk of cerebrovascular events and acute myocardial
      infarction, with the degree of carotid stenosis and presence of ischemic heart
      disease as the most important predictive factors. Management can be medical (risk
      factor modification and antiplatelet therapy) or surgical (endarterectomy). In
      this review article we briefly discuss the management of asymptomatic carotid
      bruit based on the main studies published in the last few years addressing
      cardiovascular event prevention in carotid atherosclerosis.

PMID- 15861910
TI  - Evaluation of ventricular tachycardia by magnetic resonance imaging.

PMID- 15861911
TI  - [Various thoughts on ethics regarding costs of quality in cardiology].

PMID- 15861912
TI  - [Research in administration and management].

PMID- 15861913
TI  - ["A good death": perception of health personnel in French-speaking Switzerland].
AB  - AIMS: To describe the perception of "Good death" among health personnel working
      in nursing homes in French-speaking Switzerland and to identify the differential
      explanatory factors. METHODS: A cross sectional study with a self-administered
      questionnaire, adapted from the "the' new measure of concept of good death", was
      done among health personnel in 5 nursing homes (2 in Geneva and 3 from Valais) in
      spring 2004. One hundred and sixty one persons participated at the study
      representing over 90% of the personel contacted. RESULTS: Four points were
      considered hallmarks of "Good death" by more than 80% of respondents: i.e. pain
      control, serenity and peace, presence of family members or close friends, respect
      of the last will. Up to 70% further consider as important elements the support of
      health professionals, the opportunity to transmit one's values and access to
      spiritual and/or religious support. Around 50% of respondents also consider as
      important "being able to chose the place of death", "having time to prepare one
      self", "staying conscious to the end" and "having control over body functions".
      These perceptions vary according to the place of work, the sex, the training in
      palliative care, the professional experience and of the number of deaths with
      which respondents were confronted. CONCLUSION: There seems to be converging
      opinions among health personel on what "Good death" should be. Public health
      decisions makers need to be informed on this.

PMID- 15861914
TI  - [How to relate concepts and data].
AB  - The researcher have to deal with establishing the link between a theoretical
      world, world of the concepts and the empirical world, world of the data.
      Establishing a connection between concepts and data constitutes one of the most
      important and most difficult steps of the research process. This article explains
      how this consists of a translation procedure that incorporates two processes;
      measurement and abstraction. Measurement consists of selecting the instruments or
      indicators needed to translate a concept into data. Abstraction involves the
      translation, through coding and classification, of data into concepts. This
      methodological article focuses on the central questions about the design of his
      own process of translation by using theoretical references and relevant examples.

PMID- 15861915
TI  - [McGill model].

PMID- 15861916
TI  - [Significance of comforting experiences in mental health (part 1)].
AB  - This article begins with an overview of the program of research that has examined
      comforting in a variety of clinical settings (Becherraz, 2001; 2002). Then, the
      context, participants and research question for this study are presented briefly.
      The article continues with an hermeneutic analysis of patient and clinician
      narratives. This hermeneutic analysis revealed four thematic categories related
      to comforting in mental health. These consist of (a) relational, (b) embodied,
      (c) social ties and (d) contextual dimensions. Further, the distribution of the
      14 dyads along orthogonal axes as well as their composition will be presented and
      discussed. Finally, a paradigm case will illustrate all of the thematic
      categories, concluding with a brief synthesis.

PMID- 15861917
TI  - [Significance of comforting experiences in mental health. Comparison of
      experienced comfort in general care and in psychiatric care. (part 2)].
AB  - This article provides a synthesis and comparison of three hermeneutical studies
      of the meaning of the experience of comforting in post-operative, general medical
      and mental health settings (Becherraz, 2001; 2002e). The article presents the
      points of divergence and convergence regarding nursing comforting as reported by
      36 "recipient-nurse" dyads and 2 single patients (singletons). Through the course
      of this comparative analysis, comforting appeared to be comprised of four stable
      dimensions (relational, embodied, social ties and contextual) and one unstable
      dimension (spirituality).

PMID- 15861918
TI  - [Evaluation of the therapeutic education of patients using anti-vitamin K drugs
      in a cardiology/intensive care unit].
AB  - The aim of this research is to show the importance of quality in the process of
      education of the patients treated by anti-vitamins K to prevent possible
      complications related to the disease. After having drawn up a theoretical context
      on the educational process, the author wondered whether the education given in a
      cardiology service is sufficient so that the patients acquire the necessary
      knowledge that would enable them to prevent the iatrogenic risks of anti-vitamins
      K. The results of the research showed the difficulty of the educational process
      for the patient and the staff, considering a certain number of factors: the
      relatively short stay of patients, the anxiety-provoking situation of the patient
      linked with his pathology and his future. Following the results, the author
      proposed a personalized educational contract which concerns the patients but also
      people around him and the extra-hospital network.

PMID- 15861919
TI  - [Psychodynamic analysis of nurses' work in long term care units: between pleasure
      and suffering].
AB  - Motivated by the constant increase in nurses'mental health problems, the study of
      Alderson (2001)--using the psychodynamic approach of work ("Psychodynamique du
      travai")--looks at the subjective and collective experience of nursing in a
      chronic care facility. The results of the study show that the major source of
      suffering in the nurses'work experience is their perceived lack of recognition,
      of autonomy and of professional power, deficits that are largely maintained by an
      inadequate organization of the nurses'work. Suggested solutions, according to the
      nurse subjects, include a necessary transformation of work and its context.

PMID- 15861920
TI  - [Initiation into nursing care research, a tool for measuring the construction of
      nursing professional identity].
AB  - This article presents some results stemming from university research work, in
      relation with nursing training and the construction of student nurses'
      professional identity. As a tool contributing in the process of this
      construction, Research in Nursing Care (RNS), the main subject of our research,
      is an element of the training program in nursing care. In a context of
      development of the profession, we tried to clarify the meaning of RNC as part of
      training but also in the fields where care is lavished as this is a work/study
      education program. The RNC object was discussed in historical, regulatory, and
      scientific contexts. Three hypotheses were raised and put to the test; the
      followed methodology was clarified some proposals followed the analysis of the
      various data corpus obtained and some reflection tracks were initiated for the
      trainers and assistants.

PMID- 15861921
TI  - [The Fair Competition Commission watches out for the "little guy"].

PMID- 15861922
TI  - [Virus in sheep's skin].
AB  - In a double sense, the ovine gamma herpesvirus type 2 (OvHV-2) is a virus in
      sheep's skin. Not only is it present world wide in all sheep breeds but also it
      causes malignant catarrhal fever (MCF) in cattle pigs, elk, and bison. OvHV-2
      cannot be propagated in cell culture. Therefore, new results from OvHV-2 research
      are based on molecular techniques and may be summarized as follows. OvHV-2 is
      transmitted by respiratory routes as well as by sexual intercourse. Lambs are
      infected within the first few months of life. Leucocytes, primarily latently
      infected lymphocytes, are responsible for disseminating the virus over the entire
      organism. On rare occasions, virus particles could be visualized by electron
      microscopy in explanted lymphocyte cultures. Structural antigens were detected by
      immunohistology in M-cells of diseased rabbits. Immunologically and cell
      biologically active genes have been detected on the viral genome.The products
      arising from those are thought to fine balance, the number of latently infected
      cells in sheep and to keep them alive without causing harm. Thus, it seems that
      this balance has been found through co-evolution, favoring both virus and natural
      host. In contrast, other host species that were exclude from the process of co
      evolution, are bound to fall from MCF.

PMID- 15861923
TI  - [Food hypersensitivity dermatitis in the dog: diagnostic possibilities].
AB  - Dogs with food hypersensitivity usually develop chronic pruritic dermatoses
      virtually indistinguishable from atopic dermatitis. These reactions are often
      called food allergy but the pathogenesis is poorly characterized. Several studies
      have addressed the incidence of canine adverse reactions to food but the outcomes
      were conflicting. The gold standard for the diagnosis of such a condition is the
      restricted dietary trial and the subsequent provocation challenge. Some attempts
      have been made to develop serological tests but none of these tests accurately
      predicted canine food sensitivity. The aim of the present study was to determine
      the incidence of food hypersensitivity dermatitis and to evaluate a newly
      developed serological test for the diagnosis of food allergy in dogs. Only 9% of
      55 dogs with dermatological signs compatible with food hypersensitivity or atopic
      dermatitis have been diagnosed as food hypersensitive dogs. The repeatability of
      the serological test has shown to be insufficient.

PMID- 15861924
TI  - A radiological study of the incidence of unilateral canine hip dysplasia.
AB  - The authors reviewed pelvic radiographs of 891 dogs in a retrospective study, to
      determine the incidence of Unilateral Canine Hip Dysplasia (UCHD). Results show
      that 149 (16.7%) dogs had UCHD. Comparing dogs affected uni- and bilaterally,
      results show a maximum of 37.6% with UCHD in dogs less than 12 month old, 22.8%
      in dogs between 12-24 months of age, 25.5% in dogs between 25-72 months and 14.1%
      in dogs older than 73 months.

PMID- 15861925
TI  - [Sustainable animal health and food saftey in organic farming: report of the
      second workshop of the SAFO-network].

PMID- 15861926
TI  - Heterogeneity in the evaluation of observational studies by Italian ethics
      committees.
AB  - OBJECTIVE AND METHOD: In Italy, observational research is rarely brought to the
      attention of ethics committees (ECs). This study assessed to what extent the
      observational studies conducted within the Careggi Hospital (2000 beds) and
      retrieved from MEDLINE after their publication could be traced back from the
      registries of our EC. Another aim was to compare the different opinions expressed
      by 28 ECs throughout Italy about the same multi-centre clinical protocol (an
      oncologic observational study). RESULTS: Our analysis shows that, in this sample
      of observational studies, the rate of submission to the EC is 0%. In the second
      part of our study, the evaluations of the same protocol by the different ECs were
      extremely different and ranged from unconditioned approval to rejection.
      CONCLUSION: Our proposal is that clinicians should always notify their
      observational studies to ECs. On the other hand, ECs should simply accept the
      observational protocols (without introducing any modifications except cases of
      macroscopic errors). The heterogeneity in the evaluation of a single protocol by
      different ECs raises the need to develop some forms of intervention to solve this
      source of inconsistency.

PMID- 15861927
TI  - Action research: a valuable research technique for service delivery development.
AB  - The evaluation of healthcare practice and service delivery is fraught with
      difficulties. Service development and/or delivery occurs within socially dynamic
      settings which are in a continual state of change. Service development also often
      involves large elements of improvisation. The action research approach is useful
      for health service research, as it supports collaboration between researchers and
      practitioners, and not only allows but makes explicit that the action researcher
      has both roles within the setting being studied. This paper discusses action
      research methodology and offers insight into principles that favor its use for
      service delivery development. This includes consideration of the interactive
      variables within studies of health care systems and the importance of evaluating
      relationships between stakeholders to understand how these factors or variables,
      which cannot be controlled for, are responsible for successful development of the
      service. Action research facilitates change and helps bridge the theory-practice
      gap. With the current dynamic changes within both the pharmacy profession and
      national health services, researchers may find the action research technique of
      value when considering new roles and innovative ways of engaging in
      collaborative, multi-disciplinary working to improve delivery of patient care.

PMID- 15861928
TI  - The argument for pharmaceutical policy.
AB  - Pharmaceutical policy is a global concern. It has become a hot political topic in
      most countries--developed as well as developing--and can be found on the agenda
      of international organizations such as WHO, OECD, EU, WTO and even the World
      Bank. Pharmaceutical policy affects everyone in the world of pharmacy and it is
      therefore imperative that it be understood, discussed and debated within the
      pharmacy profession and included in the curriculum of schools of pharmacy. This,
      the first article in a series, argues for the importance of the academic
      discipline of pharmaceutical policy analysis and the involvement of pharmacists
      in this endeavour. The aim of the authors is to stimulate an informed and
      critical appreciation of this field. The authors begin with an introduction to
      the field of pharmaceutical policy, introducing several important concepts and
      current trends including: medicines regulation; how pharmaceutical policy is
      made; pharmaceutical policy as a dynamic process; and the new public health as a
      global issue. The article ends with a short description of the remaining five
      articles in the series which will deal with important aspects of pharmaceutical
      policy. The topics include: economic pressures on health care systems; drug
      utilization from the clinical viewpoint (rational use of medicines); the impact
      of pharmaceutical policy on patients and the patient impact on pharmaceutical
      policy; the professional perspective; and finally the last article which deals
      with studying and evaluating pharmaceutical policy.

PMID- 15861929
TI  - Withdrawal symptom after discontinuation of transdermal fentanyl at a daily dose
      of 0.6 mg.
AB  - Neurophysiologic disorders developed in three patients after discontinuation of
      transdermal fentanyl (TDF) at a daily dose of 0.6 mg (2.5 mg per a patch),
      although direct removal of a 2.5 mg patch is permitted by the manufacturer as the
      formulation has the lowest fentanyl content among all the commercially available
      patch formulations. These observations indicate that the discontinuation of TDF
      carries a risk for developing withdrawal symptoms even when using a 2.5 mg patch.
      To avoid such adverse events, we considered the necessity of gradual reduction in
      the daily fentanyl requirements. For this purpose, we covered part of the
      application surface of the patch with an insulating tape, and then increased the
      covered area in a stepwise manner. There were no apparent withdrawal signs during
      the procedure described above.

PMID- 15861930
TI  - The complexity of achieving anticoagulation control in the face of warfarin
      phenytoin interaction: an Asian case report.
AB  - Phenytoin has been reported to have major interactions with warfarin. Phenytoin
      induces warfarin's metabolism. However, there are many case reports which provide
      conflicting conclusions. Here, we report a case of a 65-year-old man with
      mechanical heart valve on chronic warfarin therapy who experienced persistent
      fluctuations of INR and bleeding secondary to probable warfarin-phenytoin
      interactions. The patient's anticoagulation clinic visits prior to
      hospitalization were thoroughly evaluated and we continued to follow-up the case
      for 3 months post-hospitalization. The reported interaction could be reasonably
      explained from the chronology of events and the pattern of INR fluctuations
      whenever phenytoin was either added or discontinued from his drug regimen.

PMID- 15861931
TI  - Pharmacogenetics as a tool in the therapy of schizophrenia.
AB  - AIM: This review summarises the present knowledge of associations between
      pharmacogenetics and therapeutic efficacy and side effects of antipsychotics to
      enable pharmacists to judge the applicability for a more tailor made therapy in
      patients with schizophrenia. Polymorphisms of Cytochrome P450 isoenzymes and
      neurotransmitter receptors involved in the efficacy and side effects of
      antipsychotics are highlighted in this review. METHOD: A search was performed in
      Medline and EMBASE for the period 1995-August 2002. Also relevant references from
      the selected papers were incorporated. RESULTS: Poor metabolism with respect to
      CYP2D6 seems to be related with more pronounced extrapyramidal symptoms and more
      specifically with a higher incidence of tardive dyskinesia. The C/C-genotype for
      CYP1A2 results in smokers in a reduction of enzyme activity, but an effect on the
      incidence of tardive dyskinesia is controversial. For dopamine D2 receptors the
      effect of the -141C Ins/Del polymorphism on efficacy is not clear yet, although
      the Taq I polymorphism is associated with greater improvement of positive, but
      not negative symptoms in acute psychosis. The Gly9-allele of the dopamine D3
      receptor is associated with the response to clozapine, but in studies in which
      the choice of antipsychotics is not restricted, the role of this polymorphism is
      unclear. The reverse is applicable to the dopamine D(4.2/4.7) polymorphism. For
      the 5-HT2A receptor the His452Tyr polymorphism is associated with response to
      clozapine, the 102 T/C polymorphism leads to equivocal results. The polymorphism
      studied for 5-HT5A, 5-HT6, alpha1A- and alpha2A-receptors give no clear
      associations with the response to clozapine. The polymorphism studied of the
      dopamine D2 and D4 receptor are not related to extrapyramidal adverse effects and
      side effects, respectively. The 9Gly-variant of the dopamine D3 receptor, the
      102C-variant, but not the His452Tyr polymorphism of the 5-HT2A-receptor and the
      23Ser-variant (for females only) of the 5-HT2C receptor seem to increase the
      susceptibility to tardive dyskinesia. Weight gain induced by antipsychotics seems
      to be associated with the -759C-allele of the 5-HT2C receptor. CONCLUSION: The
      results show the first careful steps toward application of pharmacogenetics in a
      more individualised, tailor-made, pharmacotherapy. A pre-condition seems to be a
      multifactorial approach, as can be expected for multifactorial processes.

PMID- 15861932
TI  - Antifungal drugs and rational use of antifungals in treating invasive
      aspergillosis: the role of the hospital pharmacist.
AB  - AIM: This review discusses the most common used antifungal agents in the
      treatment of invasive fungal infections. In addition, guidelines for the
      treatment of invasive aspergillosis, as used in the Ghent University Hospital,
      are described. Moreover, the importance of determining the effectiveness of
      antifungal therapy as well as the potential role of the hospital pharmacist in
      the management of this infection is highlighted. METHODS: A review of the English
      language literature was conducted using the MEDLINE database and scientific
      websites. Search terms including antimycotics, antifungal therapy and invasive
      aspergillosis were used to refine the search, and preference was given to studies
      published after 1992. This was completed with recent treatment guidelines.
      RESULTS: An overview of the most recent advances in antifungal therapy is
      described. In addition, a flowchart for treatment of invasive aspergillosis
      (proven, probable or possible) has been developed. CONCLUSION: Invasive fungal
      infections will remain a frequent and important complication of modern medicine.
      Considering the clinical and financial outcome of invasive fungal infections, the
      role of the hospital pharmacist can be a paramount to the treatment.

PMID- 15861933
TI  - Patient information leaflets--patients' comprehension of information about
      interactions and contraindications.
AB  - OBJECTIVE: To determine how well patients could correctly recognize and
      comprehend the various information items on patient information leaflets, and to
      explore the reasons underlying poor comprehensibility. METHODS: Leaflets from 30
      randomly selected, commonly prescribed medicines were examined by experts using
      protocols to evaluate leaflet layout, language and content. The same leaflets
      were also evaluated by patients who had their medicines dispensed at 24 randomly
      selected Swedish pharmacies. A questionnaire was used for the patients'
      examination. RESULTS: The results showed that most information on the leaflets is
      sound and is well comprehended by the patients. For two information items
      regarding 'risks of interactions' and 'contraindications' the patient scores were
      low, indicating poor comprehensibility. CONCLUSION: Leaflets with low scores on
      warnings of interactions and contraindications were found to deliver more complex
      messages to older patients as compared to leaflets with high scores for these
      items.

PMID- 15861934
TI  - Initial benzodiazepine use and improved health-related quality of life.
AB  - OBJECTIVE: The health-related quality of life (HRQOL) of initial benzodiazepine
      users was measured over time. Furthermore, benzodiazepine usage characteristics
      as determinants of change in mental and physical health status of the
      benzodiazepine users were examined. METHODS: In the only pharmacy of a Dutch
      community of 13,500 and during four months from November 1994, all patients with
      a benzodiazepine prescription and no history of benzodiazepine use over a period
      of 12 months before inclusion, were invited to participate. A total of 106
      initial benzodiazepine users were matched for age and gender. In a six-month
      follow-up study, HRQOL was measured with the RAND-36. Consequently, in a nested
      case control design, determinants of change in mental and physical functioning
      over the six-month period were analysed using the Mental Component Summary and
      the Physical Component Summary. RESULTS: At baseline, initial benzodiazepine
      users showed a lower HRQOL as compared to reference subjects. After six-month
      follow-up, benzodiazepine users presented an absolute increase in HRQOL, while
      the reference subjects maintained a stable HRQOL. Diazepam and the male gender
      were associated with an increase in physical functioning over time. Younger age,
      a lower daily dose (DDD < 0.75) and a period of use between 16 and 60 days were
      associated with better mental functioning over time. CONCLUSION: This study is
      one of the first to associate improvement in HRQOL over time of starting
      benzodiazepine users with specific usage characteristics, such as limited
      duration of use and a low dosage.

PMID- 15861935
TI  - Desire for information about drugs: a survey of the need for information in
      psychiatric in-patients.
AB  - BACKGROUND: Promoting therapy adherence requires understanding various
      psychosocial parameters, including patients' need for information. Drug
      information adapted to patients' needs may empower them and increase their
      confidence in drug therapy. OBJECTIVES: To explore psychiatric in-patients'
      information preferences and to test the reliability of a Dutch version of the
      Intrinsic Desire for Information (IDI) scale in psychiatric institutions in
      Flanders. METHODS: Standardised interviews were conducted with psychiatric
      patients in 11 hospitals. The interview consisted of the IDI-scale and five open
      questions. Patient demographics collected were sex, age, number of medicines
      taken, diagnosis, number of admissions during the past year, marital status,
      education level and occupation. RESULTS: 279 patient interviews were completed. A
      factor analysis on the original 12-item scale yielded 3 factors. An abbreviated
      scale was derived from the first factor (F1). This 6-item scale measured 'extent
      of information desired:' (EID) and consisted of six items (Cronbach's alpha =
      0.73). A second factor (F2) measured 'information provider preference' (IPP)
      (alpha = 0.56) and a third factor (F3) measured 'inhibited information desire'
      (IID) (alpha = 0.69). EID was associated with number of medicines taken, duration
      of hospitalisation and marital status. CONCLUSION: The internal reliability of
      the EID-factor appears to be reproducible in the specific setting of psychiatric
      hospitals. It may be useful to help healthcare professionals develop
      pharmaceutical care towards psychiatric patients. Validation of the scale remains
      to be completed. Information need in psychiatric in-patients measured by the EID
      score was comparable to the need measured in general hospitals during earlier
      research in England. Targeted information services seem to be desirable to
      enhance therapy adherence and quality of life in psychiatric patients.

PMID- 15861936
TI  - Consumers' perceptions of community pharmacy in Portugal: a qualitative
      exploratory study.
AB  - OBJECTIVE: Pharmacists are health professionals who are ideally positioned to
      perform a primary health care role. However, the definition of professional value
      needs to be considered not just as professional education and skills, but also in
      terms of how consumers perceive it. The main aim of this work was to explore the
      public's perceptions and attitudes towards community pharmacy in Portugal.
      METHODS: A pure qualitative approach was undertaken. The data were collected
      through a semi-structured interview, conducted with a 'snowball' like sample.
      First, individuals (n = 15) were interviewed, allowing for adjustment and
      validation of the interview schedule, followed latter by group interviews with
      adults in rural and urban areas. Group participants (n = 25) were asked about
      their behaviour and beliefs, resulting from their perceptions of community
      pharmacies, pharmacists and medicines. Future expectations regarding the
      community pharmacy service were also explored. The interviews were tape recorded
      and transcribed verbatim. An iterative, reflexive coding process was applied,
      assisted by the qualitative software package QSR NUD*IST v4. The inductive
      analysis of the extracted codes assembled those codes into themes. RESULTS AND
      DISCUSSION: This article will mainly focus on community pharmacy service
      representations and cognitions (theme A) and community pharmacy evaluative
      perceptions and behaviours (theme B). Participants displayed general and
      contradictory ideas about the actual functions of the pharmacist, including weak
      conceptualizations and a positive demand for services in relation to product
      supply. This superficial understanding is in line with previous results from
      satisfaction studies, confirming a low expectation level. The public's poor
      knowledge and low expectations can justify a reduced desire for an extended role
      of the pharmacist in the community. This uncertain service conceptualization does
      not define the professional responsibility from a consumer's perspective.
      CONCLUSIONS: Although these results allow for the development of a framework to
      describe the perceptions of community pharmacy users, further research is needed
      to determine the prevalence of these and other possible results.

PMID- 15861937
TI  - Development of the specialist menopause pharmacist (SMP) role within a research
      framework.
AB  - OBJECTIVE: To determine the potential contribution of a new healthcare practice
      model, the specialist menopause pharmacist (SMP) role. METHOD: Post pilot, the
      SMP's remit was proposed as combining clinical practice (service delivery) and
      research studies, with emphasis on strengthening liaison between the secondary
      and primary care sectors. Action research, a qualitative research technique, was
      selected to document role development in the first year. Here the pharmacist
      researcher's focus was a local situation where the effects of a particular
      change, involving people who were part of the situation, were assessed. The
      change factor was the introduction of the pharmacist to the multi-disciplinary
      specialist team. The pharmacist-researcher did not attempt to hold anything
      constant but observed the changes occurring in a systematic manner. Analysis of
      on-going collaborative professional activity generated the hypothesis that the
      role was of use in enhancing patient care. Using triangulation and focusing on
      the descriptive phrase 'of use', it was then possible to study SMP implemented
      'actions' that would be accepted as being 'useful' SMP functions. The aim was to
      test for reliability and obtain data with greater range and accuracy. The three
      studies undertaken included a controlled, questionnaire study asking for
      patients' views on the pharmacist service, auditing health professionals usage of
      the pharmacist operated telephone help-line, and assessing the impact of
      structured on-site training on community pharmacists. MAIN OUTCOME MEASURE:
      Overall impact and achievements over 3 years, against a background where the SMP
      role continued to develop during the study. RESULTS: Action research methodology
      engendered reflective practice, enabling the SMP to be both the service delivery
      provider (the intervention) and the researcher. This pharmacist practice model is
      accepted both by patients and health professional colleagues. The remit combines
      clinical practice with on-going research studies. In the UK setting, the SMP can
      undertake numerous liaison activities between secondary and primary care sectors
      to facilitate enhanced delivery of menopause patient care. CONCLUSION: Using an
      action research approach, and combining qualitative and quantitative methods to
      complement data collection, it was possible to assess the specialist pharmacist
      role in depth.

PMID- 15861938
TI  - The role of the IPSS (International Prostate Symptoms Score) in predicting acute
      retention of urine in patients undergoing major joint arthroplasty.
AB  - BACKGROUND: Acute urinary retention following major joint arthroplasty is common.
      It does necessitate instrumentation, puts patients at risk of complications, and
      causes discomfort and embarrassment. The aim of the study was to find a test to
      help the surgeon to predict the possibility of acute retention of urine. METHODS:
      Male patients admitted for elective major joint arthroplasty filled in an IPSS
      (International Prostate Symptoms Score) during the pre-operative visit. They were
      observed post-operatively to document if they passed urine spontaneously or went
      into acute retention. RESULTS: There was a strong correlation between the IPSS
      and the likelihood of developing acute retention. Patients with moderate to high
      IPSS had a 55% to 100% chance of developing acute retention of urine,
      respectively. CONCLUSION: The IPSS proved to be a simple and reliable test to
      help the surgeon in predicting the possibility of developing acute retention. It
      might be a good addition to the pre-admission clinic investigations in patients
      undergoing major surgery. It could consolidate the decision to pre-emptive
      catheterisation in patients at risk.

PMID- 15861939
TI  - Fine needle aspiration cytology in the management of a parotid mass: a two centre
      retrospective study.
AB  - OBJECTIVES: There is a diversity of opinion regarding the role of fine needle
      aspiration cytology (FNAC) in the pre-operative evaluation of the parotid mass.
      This study further investigates the role of FNAC from the standpoint of the
      clinician attempting to resolve one or more clinical issues. METHODS: A
      retrospective study conducted at two UK Hospitals with no overlap of
      cytopathologists or surgeons. Patients undergoing parotidectomy at each
      institution were identified from Pathology department databases. The definitive
      histopathological diagnosis was compared with any pre-operative FNAC diagnosis.
      Cytology results were classified as suggestive, non-diagnostic, sampling error,
      or misleading. SETTING: The study was conducted in a District General Hospital
      and a University Teaching Hospital providing secondary care for each community.
      RESULTS: For the University Teaching Hospital the sensitivity in distinguishing
      malignant from benign disease was 79% (95% CI 61-97%) with a specificity 84% (95%
      CI 73-95%). However, three of eight patients with a primary parotid salivary
      gland malignancy were reported as having benign disease on FNAC. For the
      participating District General Hospital the sensitivity in distinguishing
      malignant from benign disease was 38% (95% CI 13-63%) and specificity 95% (95% CI
      73-95%). CONCLUSIONS: Fine needle aspiration cytology does not reliably
      distinguish a benign from a malignant primary salivary gland neoplasm in the
      participating institutions. Where clinical teams use FNAC in an attempt to
      resolve this clinical problem, the results should be interpreted with caution and
      an ongoing audit of performance is required.

PMID- 15861940
TI  - Comparison between three therapeutic modalities for non-complicated pilonidal
      sinus disease.
AB  - OBJECTIVE: To evaluate the outcome of each of the three methods used to treat
      pilonidal sinus disease. STUDY DESIGN: A prospective blind randomised study.
      MATERIALS AND METHODS: Between April 2000 and February 2003, 83 patients (68 male
      and 15 female), aged between 19 and 31 years (mean 26.6), scheduled for elective
      operations for pilonidal sinus disease. Patients were randomly assigned to
      receive one of three excisional surgical procedures. Group A consisted of 28
      patients (22 males and six females) and underwent wide resection of the skin and
      subcutaneous tissue of the natal cleft, followed by primary closure of the wound
      in two layers after insertion of suction drain. Group B consisted of 26 patients
      (22 males and four females) and underwent wide resection of the skin and
      subcutaneous tissue and their wounds left opened for secondary intention healing.
      Group C consisted of 29 patients (24 males and five females) and underwent
      limited excision of the fistulous tract and their wounds were left opened for
      secondary intention healing. Patients were followed-up for 15 to 48 months post
      operatively. Demographic data, operative time, hospital stay, operative blood
      loss, post-operative pain, wound healing time and patient's satisfaction were
      recorded. RESULTS: The limited excision group of patients had a highly
      significant shorter operative time than the closed wound group of patients
      (p<0.001). They also had the shortest hospital stay, operative blood loss and
      post-operative pain (p<0.001). The closed wound group of patients showed
      significantly shortest wound healing time, followed by the limited excision group
      of patients; the wide excision group of patients showed the longest healing time.
      Apart from the minimal non-significant elevation of the rate of recurrence in the
      closed wound group of patients, there was no difference between the three groups.
      All recurrent cases were obese patients and presented within the first six months
      after operations. CONCLUSION: Limited excision of a pilonidal sinus represents
      one of the best therapeutic options. The result of this method is comparable with
      the more aggressive frequently used excisional method, and it has the advantage
      of having a shorter convalescence and better patient satisfaction.

PMID- 15861941
TI  - Surgical treatment of metastases to the pancreas.
AB  - BACKGROUND AND AIMS: Metastases to the pancreas are rare and their surgical
      treatment is not well reported. We present a considerable experience from a
      single centre analysing various prognostic factors. METHODS: Data were collected
      on 13 cases who underwent surgery between 1988 and 2002. Since 1997, data have
      been recorded prospectively on a dedicated database. Clinical and
      histopathological factors were reviewed. RESULTS: There were two women and 11 men
      with a median age of 62 years (range 40-73). There were seven cases of renal cell
      carcinomas, three colorectal carcinomas, two sarcomas and one lung carcinoma. A
      prolonged disease-free interval from primary surgery was characteristic for renal
      cell carcinoma cases (median = 10.8 years). The operative procedures performed
      included seven pancreatoduodenectomies, four total and two distal
      pancreatectomies. The operative mortality and morbidity was 7.7% and 46.1%
      respectively. The overall one- and two-year survival was 78.8% and 54%
      respectively. Median survival for renal cell carcinoma was 30.5 months and for
      non-renal cell carcinoma was 26.4 months (p = 0.76). CONCLUSIONS: Pancreatectomy
      should be considered for metastases to the pancreas in the absence of generalised
      metastatic disease. However, decision making and experience should be
      concentrated in centres with significant familiarity of this approach.

PMID- 15861942
TI  - Problem-based learning: is anatomy a casualty?
AB  - INTRODUCTION: The teaching of medical anatomy is changing. Medical schools
      worldwide are moving away from dissection and lectures to a more integrated
      course, where basic science and clinical skills are taught simultaneously.
      Medical students on these integrated courses have reported a lack of confidence
      in their basic science knowledge, especially concerning anatomy. Our aim was to
      perform a randomised controlled trial (RCT) to compare anatomical knowledge of
      two groups of second-year medical students, the first group taught on a
      traditional course, the second on an integrated course. MATERIALS AND METHODS:
      Testing was done using a Questionnaire in a "True/False" format. There were 80
      students in each group. There was no penalty for an incorrect answer. The test
      was performed under examination conditions. Papers were marked under blind
      conditions. Results were analysed using a Student's t test analysis. RESULTS:
      Those students taught on a traditional course exhibited a significantly higher
      level of basic anatomical knowledge (p<0.001) than those taught on an integrated
      course. The students taught on an integrated course showed a much greater range
      of results. CONCLUSIONS: Students taught on a traditional course have a higher
      level of anatomical knowledge than those taught on an integrated course. Our
      results differ from previous studies done in Europe which show no difference
      between the courses.

PMID- 15861943
TI  - The perioperative challenge of nephrogenic diabetes insipidus: a
      multidisciplinary approach.
AB  - Nephrogenic Diabetes Insipidus (NDI) is characterised by the inability of the
      kidneys to concentrate urine in response to arginine vasopressin (AVP). Such
      patients typically experience polyuria and polydipsia because of this inability
      to autoregulate their water balance. This provides a perioperative challenge that
      could lead to a life-threatening situation. This article documents a patient with
      NDI who underwent an elective bowel re-anastomosis. Two peak serum sodium values
      were attained. The first when the patient was retaining sodium due to an
      inappropriate fluid regimen and the second due to hypovolaemia. The literature is
      reviewed and principles for NDI perioperative management are proposed.

PMID- 15861944
TI  - Traumatic rupture of the aorta in an 11-year-old patient: surgical considerations
      in the technique of repair.
AB  - We describe an 11-year-old child who presented with a traumatic aortic
      transection. This is an extremely rare occurrence in this age group. In managing
      the injury the future growth of the child must be considered. Primary repair is
      ideal when possible, but in choosing a graft, the choice of size and material
      should take cognisance of the risk of a coarctation-like syndrome in the future.

PMID- 15861945
TI  - Edinburgh connections in a painful world.

PMID- 15861946
TI  - Atypical presentations of emphysematous cystitis.
AB  - Emphysematous cystitis is an uncommon infection of the bladder with the formation
      of carbon dioxide either within the bladder or within its wall. It is commonly
      seen in women and those with poorly controlled diabetes mellitus, in association
      with some form of urinary stasis and obstruction. The clinical features are very
      varied and the outcome is often unpredictable. Radiography may reveal a
      radiolucent line around the bladder wall or gas within the bladder. Occasionally,
      computed tomography scans are required to help in the diagnosis due to their
      atypical presentation with acute abdominal pain. Herein, we report three patients
      with such a condition who were treated with favourable outcomes. Of the three
      patients, two had to undergo exploratory laparotomy due to their initial
      presentations with acute abdomens.

PMID- 15861947
TI  - Paraganglioma of the cauda equina: a case report and literature review.
AB  - A 26-year-old man presented with left leg pain and progressive paraparesis.
      Imaging revealed a large intradural tumour compressing the cauda equina. The
      lesion was radically resected and histological analysis revealed it to be a
      paraganglioma. The clinical features of this rare tumour are described with a
      review of the literature.

PMID- 15861948
TI  - Re: McGregor JC. Major burn disasters: lessons to be learned from previous
      incidents and a need for a national plan. Surg J R Coll Edinb Irel 2004; 2(5):
      249-311.

PMID- 15861949
TI  - Re: McGregor JC. Major burn disasters: lessons to be learned from previous
      incidents and a need for a national plan. Surg J R Coll Edinb Irel 2004; 2(5):
      249-311.

PMID- 15861950
TI  - Re: McGregor JC. Major burn disasters: lessons to be learned from previous
      incidents and a need for a national plan. Surg J R Coll Edinb Irel 2004; 2(5):
      249-311.

PMID- 15861951
TI  - Re: King PM, Suttie SA, Jansen JO, Watson AJ. Perforation of the terminal ileum:
      a possible complication of nicorandil therapy. Surg J R Coll Surg Edinb Irel
      2004; 1: 56-57.

PMID- 15861952
TI  - Re: Anwar S, Hughes S, Eadie AJ, Scott NA. Anastomotic technique and survival
      after right hemicolectomy for colorectal cancer. Surg J R Coll Surg Edinb Irel
      2004, 281-86.

PMID- 15861953
TI  - PROSSA challenge.

PMID- 15861954
TI  - Working with the profession to maintain and enhance quality healthcare.

PMID- 15861955
TI  - Self-etching adhesives: review of adhesion to tooth structure part II.
AB  - Self-etching adhesives are steadily increasing in popularity among dental
      practitioners with their easy handling technique and their promise of no post-op
      sensitivity. As with any new bonding material, in vitro and in vivo
      investigations are required to assess the clinical efficacy of these systems.
      OBJECTIVES: The current literature was reviewed to provide information on these
      systems, including the influence of their acidity and permeability on the quality
      of the bond, the role of water in long-term degradation of the bond in in vivo
      and in vitro studies, and the clinical efficacy of the self-etching adhesives in
      clinical research studies. DATA SOURCES: Published abstracts, reviews, laboratory
      reports and clinical research papers in the dental literature. CONCLUSIONS: Very
      little information is available on self-etching systems pertaining to the long
      term in vitro and in vivo durability of their bond and their medium- to long-term
      clinical outcome. Although post-op sensitivity seems to be something of the past,
      short-term clinical studies show that some self-etching adhesives do not perform
      as well as total-etch systems.

PMID- 15861956
TI  - Idiopathic "bony bumps" in the jaws--what's in a name?

PMID- 15861957
TI  - Halitosis: a review.
AB  - Halitosis, or bad breath, is caused by mainly volatile sulfur compounds (VSC) as
      a result of bacterial breakdown of protein and can be quantitatively and
      qualitatively measured in the expired oral breath. In eight to ninety percent of
      cases, halitosis originates in the mouth due to inadequate plaque control,
      periodontal disease, dry mouth, faulty restorations, and in particular due to
      excessive bacterial growth on the posterior third of the dorsal surface of the
      tongue. In the remaining ten to twenty percent of cases, bad breath is caused by
      systemic disorders such as hepatic, pancreatic and nephritic insufficiencies,
      trimethylaminuria, upper and lower respiratory tract infection, medication and
      cases where gastric content may generate oral malodour. The methods of detecting
      or diagnosing halitosis are organoleptic or human sense of smell, sulfide
      monitoring and gas chromatography. All of these methods have limitations and
      disadvantages. A more accurate, analytical system which will be able to precisely
      detect the volatile compounds in the expired air and correlate the results to a
      specific cause is not yet available. Dental professionals require a good
      knowledge on the subject of bad breath in order to feel secure about counseling
      and managing patients suffering from this condition. The management of halitosis
      involves maintenance of plaque control, elimination of active periodontal disease
      and cleaning the tongue on a routine basis. Oral rinsing with a mouthwash could
      be indicated in some instances, as a temporary measure.

PMID- 15861958
TI  - Fibre reinforced composites--alternative for lost teeth replacement.
AB  - The loss of an anterior tooth can affect a patient psychologically and socially.
      This trauma can be minimized by the immediate replacement of the lost tooth,
      preferably using a fixed prosthesis. This paper describes the immediate
      replacement of anterior lost teeth by using fibre reinforced composite materials,
      although these techniques can be employed very successfully in the replacement of
      posterior teeth as well. The abutment teeth can be conserved, with little or no
      preparation, making this procedure truly minimally invasive and keeping the
      technique reversible. Additional advantages are that the procedure is completed
      at the chairside in a single visit, thereby avoiding laboratory costs and saving
      time while waiting for the finished prosthesis. This technique can be used as an
      interim measure or as a permanent prosthesis.

PMID- 15861959
TI  - A baseline survey: oral health status of prisoners--Western Cape.
AB  - South African prison populations continue to grow because of the escalating crime
      and an overstretched judicial system. The aim of this study was to assess the
      oral health status of prison inmates in the Western Cape (Pollsmoor, Goodwood,
      Paarl and Worcester). A cross-sectional epidemiological survey involving a
      clinical oral examination and face-to-face interviews was used to collect
      information on DMFT, periodontal health, perceived needs and the knowledge,
      attitudes and behaviour of inmates to oral health. Clinical examinations were
      carried out using WHO criteria. Of the 340 study participants, 264 were male and
      76 were female. The prevalence of oral disease was high. The mean DMFT was 15.45
      and the total DMFT increased with age. There was a reported impact on oral health
      quality of life, with many citing problems with eating, drinking and pain. Self
      reported dental needs indicated a perceived need for dentures, scaling and
      fillings. Over two thirds of the sample (72%) reported that the dental services
      that they presently receive are poor. This study found a high prevalence of
      dental caries and periodontal disease among the correctional service populations.
      There is an urgent need for the development of a basic oral health care package
      that should be offered to all inmates as eventually many of them will be
      returning to the community.

PMID- 15861960
TI  - Basic dental training. Recommended outcome (competences) of undergraduate
      training.

PMID- 15861961
TI  - General practitioner's radiology case 28. Thalassemia.

PMID- 15861962
TI  - [Primary lymphoma of the serous body cavities].

PMID- 15861964
TI  - [The painful hemiplegic shoulder: effects of exercises program according to
      Bobath].
AB  - AIM: To verify whether a shoulder exercises program according to Bobath reduced
      the shoulder pain in hemiplegic patients. METHODS: We studied a total of 20
      patients with pain shoulder. Ten patients are assigned to group R (submitted to
      rehabilitation) and ten to group R+E (submitted to rehabilitation and shoulder
      exercises program according to Bobath). Shoulder exercises program was self
      performed by the patients after training in occupational rehabilitation unit. The
      assessment of patients was performed at admission to hospital, at discharge and
      three months after discharge. Shoulder pain (VAS), shoulder range of motion,
      disability (FIM), motor function (Fugl-Meyer scale) and spasticity (Ashworth
      scale) of paretic arm were evaluated in all patients. RESULTS: VAS was similar in
      both groups at admission and decreased in group R+E at discharge without reaching
      significant differences (p=0.253). On the contrary, VAS and Shoulder range of
      motion improved statistically in group R+E (p=0.0001, p<0.04 respectively) after
      three months. The others variables measured did not change. CONCLUSIONS: This
      study showed that a shoulder exercises program according to Bobath reduces
      shoulder pain of patients with hemiplegia if it is performed daily and for a long
      period of time.

PMID- 15861965
TI  - [Effect of sulphurous Bioglea on psoriasis].
AB  - OBJECTIVE: The efficacy of biological sulphurous Bioglee on psoriasis was
      investigated using an organic matrix derived from the metabolism of microflora
      growing in shallow hyper thermal waters possessing high sulphur concentrations
      and in thermal mud at Guardia Piemontese-Acquappesa (CS). Such a matrix forms
      part of the "Sulphuretum" ecological matrix which is dominated by cyanobacteria
      and sulfobacteria. The effect of this matrix on psoriasis was evaluated through
      the typical symptoms such as desquamation, cutaneous erythema and itching.
      METHODS: The study was carried out on 20 patients wich gave informed consent,
      suffering from psoriasis. Image analysis was used to monitor the intensity of
      psoriasic lesions prior to and at the conclusion of the therapy which consisted
      of topical applications of the thermal matrices twice a day for 12 days. RESULTS:
      Image analysis illustrated a reduction in the intensity of psoriasic lesions at
      the conclusion of the therapy with significant reductions in desquamation,
      erythema and itching. CONCLUSIONS: The anti-psoriasic action of the thermal
      matrix used in this study may be attributable to the substances such as carotene,
      hydro and lipo-soluble vitamins and naturally occuring phytosterols. These
      substances may not only be anti-inflammatory but may also work synergistically
      with the mineral components of the thermal matrix to attenuate the symptoms of
      psoriasis.

PMID- 15861966
TI  - [Symptomatic management in multiple sclerosis].
AB  - Multiple sclerosis is an autoimmune disease, characyerized by demylinization of
      white matter of Central Nervous System (CNS). Its etiology is still unknown. In
      the world, about 2.000.000 of people are affected by MS, with higher prevalence
      in North-America and North-Europe. Two are the essential features of the
      therapeutical management in MS: 1) immunomodulating therapy, which consists of
      "disease modifing drugs"; 2) symptomatic treatment. Only some patients can
      benefit of immunomodulating therapy, whereas symptomatic treatment can be
      helpfull to everbody. In the following pages the authors will review the medical
      options used in the diagnostic, prognostic and therapeutic management of MS.

PMID- 15861967
TI  - [Current trends and future perspectives in the therapy of the osteoporosis].
AB  - Osteoporosis is a pathology of considerable social impact for its high frequency
      in the elderly and for serious complications of the fragility fracture.
      Osteoporosis prevention requires high bone mass peak during growth age, adult and
      elder people must limit the bone loss by taking specific daily behavior and
      nutritional measures. The pharmacological treatment is based on drugs which are
      able to change bone metabolism, among which the bisphosphonates result to have a
      good efficacy with few collateral effects, the last generation (Alendronate and
      Risedronate) may be taken once a week. Promising for the next future is the
      Recombinante Parathormon, recently approved from the Food and Drug Administration
      for osteoporosis treatment. Leptin and l'Osteoprogerin are new experimental
      molecules under study able to act on the mechanism of central and local
      regulation of bone remodeling.

PMID- 15861968
TI  - Neuroendocrinology of mood disorders.
AB  - The neuroendocrine system, which plays an important role in regulation of mood,
      is dysfunctional in patients suffering from mood disorders. In order to improve
      the quality of life for patients, additional research is needed to define
      clinical implications of neuroendocrine dysfunction in mood disorders. It would
      be important to define which specific hormonal responses that are blunted in
      affective disorders contribute to mood symptoms and which medications that
      normalize neuroendocrine function are conditioning the impact of mood symptoms.
      Consideration and evaluation of endocrine status result important in psychiatric
      patients, both to ensure proper diagnosis and adequate treatment.

PMID- 15861969
TI  - [A five year follow-up of an HHV-8 related lymphoma in an HIV-negative elderly
      patient].
AB  - Primary Effusion Lymphoma (PEL) associated with the Human Herpes Virus 8 (HHV-8),
      is a rare type of non-Hodgkin lymphoma. It mainly strikes HIV-positive men. Five
      year follow-up of a case of PEL HHV-8 related in HIV negative elderly man, is
      described. The patient was admitted to our Department for dyspnea, thoracic pain
      and persistent slight temperature. Chest radiography showed a left pleural
      effusion. Cytomorphological, immunohistochemical and molecular assays performed
      on pleural fluid, demonstrated the presence of a PEL HHV-8 related, in absence of
      Epstein-Barr virus (EBV) infection in the tumour cells. Serologic test for HIV
      (ELISA) resulted negative. Chest TC, taken after thoracentesis, showed marked
      thickening of diaphragmatic pleura. Because patient's age and general conditions,
      no chemotherapy was performed. Five years after diagnosis, clinical examination
      and chest tomographyshowed resolution of the described syndrome; particularly
      chest TC showed complete disappearance of diaphragmatic pleura thickening. This
      biological behaviour is unusually for PEL: medical literature shows that this
      lymphoma has a very poor prognosis; this case-report suggests, as already
      proposed from some authors, that PEL, in HIV-negative EBV-negative patients, is a
      distinct clinical entity, with a different clinical behaviour.

PMID- 15861970
TI  - [Old age: ethical and psychological perspectives].
AB  - PREMISED: The extension of the average life and the contraction of the births
      have generated a negative evaluation of the future social models. The old age is
      seen more as a problem than as possible resource, more as something to be
      frightened from than something belonging to all of us. ANALYSIS OF THE PROBLEM:
      The current study aims at overturning this negative point of view that sees
      senility as a continuous recourse to Medicine and not as a progressive resource
      investment, seems to be dominating today the relation of care witch seems the old
      aged needing is a connection point in dialogue among generation opens new
      possibilities of interaction. For this reason it is important to understand the
      meaning of senility for the cognitive point of view grasping the elements of
      specific richness that are important to keep obtaining a new point of view of the
      old age. CONCLUSION: Bioethics and psychology can help induce to think that
      senility is that phase of life in which the subject nevertheless all the psycho
      physical limitations, individualises the answer to important questions of life
      and death, that are removed when the pragmatic realization is more pursuing.

PMID- 15861971
TI  - [Osteoarthrosis].

PMID- 15861973
TI  - [Presidential address of the 40th annual meeting of the GEM].

PMID- 15861972
TI  - [Dietetic management of cystic fibrosis: intervention strategies].
AB  - Cystic fibrosis is a systemic disease whose prognosis has improved thanks
      multidisciplinary researches and above all better knowledges and care of
      nutritional problems. It is important, for a good therapy, considering each case
      singularly, with a differentiated and individualized dietetic approach, which
      focuses on its specific needs and features. A "step by step" process could be
      useful to manage patient suffering from cystic fibrosis; it is based on 5
      different patterns of possible nutritional dietetic methods. The development of
      the nutritional techniques of treatment for this kind of desease both with the
      individualized and differentiated approach have led to improve prognosis and
      especially the patient's standard of life.

PMID- 15861974
TI  - [Science and truth].

PMID- 15861975
TI  - [Surgical anatomy of the dorsal face of the hand and the wrist].
AB  - The anatomical knowledge of the dorsal aspect of the hand has been enriched these
      last years by a more surgically applied approach, especially of that of its
      integument and blood supply. The vascularization of the superficial nerves, the
      anastomoses between the dorsal and palmar arterial networks has allowed designing
      new flaps, ante- and retrograde, usable in the coverage of more and more distal
      defects. The extensor apparatus shows many anatomic variations, often
      asymptomatic, except the extensor digitorum brevis manus muscle, which can mimic
      a mass at the dorsal aspect of the hand.

PMID- 15861976
TI  - [Scaphocapitate arthrodesis for chronic scapholunate instability: a retrospective
      study of 13 cases].
AB  - The management of chronic instability of the scapholunate joint is controversial.
      We have opted for scaphocapitate arthrodesis in such cases. The aim of this study
      was to analyse the clinical and radiological results of this procedure. Between
      1997 and 2001, 13 scaphocapitate arthrodesis were performed for this indication.
      Eleven using two screws, one using a single screw plus a staple, and one using a
      single staple alone. The average age of the patients was 40 years. There were 8
      sport accidents and 5 work accidents. The average follow-up was 26 months. We
      analysed the functional results and measured the height of the carpus and the
      radio-lunar angle radiographically. We noticed a mobility loss of between 20 and
      40%, especially for radial tilt and flexion. The grip strength was improved. All
      the patients except one have some residual pain. We noted three non-unions which
      required revision with eventual final consolidation. The height of the carpus was
      improved. The average radio-lunar angle at follow-up was 16 degrees. Only one
      wrist remained in DISI. The mobility of the wrist was decreased by this
      procedure. In all these cases the dorsal approach to the wrist which we employed
      was bound to decrease the mobility. The radial tilt was decreased due to the
      partial arthrodesis. This procedure restore the height of the carpus and
      partially corrects the DISI. As we were not able to obtain a pain free wrist
      through our procedure, we raise the question as to whether a total neurectomy of
      the wrist should be performed at the same time.

PMID- 15861977
TI  - [Surgery for pseudarthrosis of humeral shaft fractures: a retrospective series of
      21 cases].
AB  - INTRODUCTION: The morbidity of surgery for non-union of the humerus is not
      insignificant: the aims of this retrospective study were to study the results of
      these rather difficult procedures and to make some logical suggestions regarding
      surgical technique. PATIENTS AND METHODS: Between 1996 and 2000, 21 patients had
      a surgical procedure for non-union of the humeral shaft. At follow-up, the mean
      age was 40 years. The causes of the initial trauma were: 12 road accidents, seven
      standing height falls, one fall from a window, one farm machine accident. The
      commonest fracture site was the middle third. In 17 procedures, we performed
      plate osteosyntesis. Three patients were treated by external fixator because of
      infection. In one patient we used a nail. For the follow-up evaluation, we used
      the score of the Western Orthopaedic Society. RESULTS: According to the "WOS"
      score evaluation, we noted: ten very good results, five good results, three poor
      results and one bad result. The bad result corresponded to the patient in whom
      consolidation was not obtained. DISCUSSION AND CONCLUSION: Management of non
      union of the humerus should be by immediate surgery. The best treatment of non
      union of the humerus is its prevention by correct management of the initial
      fracture.

PMID- 15861978
TI  - [Retrograde intramedullary nailing for humeral shaft fractures in adults.
      Evaluation of anatomical and functional results in 63 cases].
AB  - PURPOSE OF THE STUDY: Many methods have been proposed for treatment of displaced
      humeral shaft fractures in adults. This study was designed to evaluate the
      anatomical and functional results of patients treated by retrograde
      intramedullary nailing through the lateral condyle. MATERIALS AND METHODS: Sixty
      three fresh traumatic fractures of the humerus were treated between January 2000
      and January 2003. Five patients were lost to follow-up. The AO classification and
      the Hackethal classification modified by De La Caffiniere were used. Outcome was
      assessed according to the modified Stewart and Hundey classification. RESULTS: We
      had 23 very good results, 26 good results, five passable results and four bad
      results. The bad results were three cases of non-union and one case with poor
      function (stiffness of elbow and shoulder). Mean delay to union was ten weeks
      four days. There were no cases of iatrogenic radial nerve palsy or pin migration.
      CONCLUSION: Retrograde intramedullary nailing is a reliable method, easy to
      perform and of low economic cost. We propose it for all types of displaced shaft
      humeral fractures.

PMID- 15861979
TI  - [Glomus tumor of forearm: a case report].
AB  - The authors report a case of a glomus tumor of the soft-tissues of the forearm in
      a 23 year old woman. The diagnosis was suspected on MRI, and confirmed by a
      biopsy. The result after surgical resection was excellent, just like other cases
      in the literature.

PMID- 15861980
TI  - [Isolated dislocation of the radial head in an adult (case report and literature
      review)].
AB  - The authors report a case of isolated anterior dislocation of the radial head in
      a 28-years-old woman without functional disorders. After a literature review,
      they discute traumatic and congenital etiology of this injury.

PMID- 15861981
TI  - [Total carpometacarpal dislocation. Case report].
AB  - Anterior carpometacarpal dislocation are rare injuries. The anterior type is
      exceptional. Mr A.T 18 years old, male, student, right-handed, without
      pathological medical history. He was admitted in emergency after a fall of a
      motorbike (unknown mechanism) for a closed left hand injury; examination revealed
      a total impaired mobility and an important swelling of the hand without
      vasculonervous disorders. X-ray revealed a pure anterior dislocation of the five
      carpometacarpal joints. The patient was operated on in emergency using both
      anterior and posterior approach, which allowed to reduce the dislocation. It was
      maintained by K-wires. An antebrachiopalmar cast was applied for six weeks. One
      year later, the result obtained was considered excellent.

PMID- 15861982
TI  - [Reorientation of the distal radial articular surface in Madelung's deformity by
      a reversed cuneiform osteotomy].
AB  - A technique of cuneiform osteotomy of the distal end of the radius is presented.
      It was used in three female patients with Madelung's deformity (two bilateral
      cases and one unilateral case). A wedge of bone was harvested in situ from the
      metaphysis, then returned and replaced in situ. This technique, performed through
      the Henry's approach, combines closing wedge osteotomy on the longer radial
      cortices with opening wedge osteotomy on the shorter radial cortices. The biplane
      osteotomy, which provides the bony wedge, involves the entire width of the
      metaphysis and is performed with an oscillating saw. Once the wedge is reversed
      and replaced, stabilization is obtained with an anterior plate. In all five cases
      the forward subluxation of the carpus was reduced as well as the distal
      radioulnar dislocation through the backward projection of the epiphysis. The
      reversed cuneiform osteotomy brings new possibilities of reorienting the radial
      articular surface and its technical mastery allows for accurate correction of
      severe deformities.

PMID- 15861983
TI  - [Understanding tendon pulley ruptures in rock climbers].

PMID- 15861984
TI  - Contemplating the assessment of great river ecosystems.
AB  - The science and practice of assessing the status and trends of ecological
      conditions in great rivers have not kept pace with perturbation wrought on these
      systems. Participants at a symposium sponsored by the U.S. Environmental
      Protection Agency (USEPA) and the Council of State Governments concluded that
      useful and efficient assessments of great river ecosystems require thoughtful
      alignment of sampling designs, spatial and temporal scales, indicators,
      management needs, and ecosystem characteristics. Site-specific physical,
      chemical, and biological data long accumulated by monitoring programs have value
      but fail to provide the integrated system-wide perspective required for adaptive
      management and the Clean Water Act. Use of existing data may be limited by
      methodological incompatibilities, access difficulties, and the exclusive
      applicability of data to specific habitats or sites. The transition from site
      specific to system-wide assessments benefits from research being done by USEPA's
      Environmental Monitoring and Assessment Program (EMAP) and other programs that
      use probability surveys and biological indicators. Indicators of various taxa (in
      particular fish, algae, and benthic invertebrates) have been successfully
      developed for great rivers. However, optimizing the information these ecological
      indicators convey to managers and the public is the subject of ongoing research.

PMID- 15861985
TI  - Environmental monitoring and assessment of a Great River ecosystem: the Upper
      Missouri River pilot.
AB  - Most Great River ecosystems (GREs) are extensively modified and are not receiving
      adequate protection to prevent further habitat degradation and loss of biotic
      integrity. In the United States, ecological monitoring and assessment of GREs has
      lagged behind streams and estuaries, and the management of GREs is hampered by
      the lack of unbiased data at appropriate spatial scales. Properties of GREs that
      make them challenging to monitor and assess include difficult sample logistics
      and high habitat diversity. The U.S. Environmental Protection Agency's
      Environmental Monitoring and Assessment Program (EMAP) has developed a
      comprehensive, regional-scale, survey-based monitoring approach to assessment of
      streams and estuaries, but has not yet conducted research on applying these tools
      to GRE monitoring. In this paper we present an overview of an EMAP research
      project on the Upper Missouri River (UMR). We summarize the assessment objectives
      for the study, the design for selecting sample locations, the indicators measured
      at these sites and the tools used to analyze data. We present an example of the
      type of statements that can be made with EMAP monitoring data. With modification,
      the set of methodologies developed by EMAP may be well suited for assessment of
      GREs in general.

PMID- 15861986
TI  - How probability survey data can help integrate 305(b) and 303(d) monitoring and
      assessment of state waters.
AB  - Section 305(b) of the United States' Clean Water Act (CWA) requires states to
      assess the overall quality of waters in the states, while Section 303(d) requires
      states to develop a list of the specific waters in their state not attaining
      water quality standards (a.k.a impaired waters). An integrated, efficient and
      cost-effective process is needed to acquire and assess the data needed to meet
      both these mandates. A subset of presentations at the 2002 Environmental
      Monitoring and Assessment Program (EMAP) Symposium provided information on how
      probability data, tools and methods could be used by states and other entities to
      aid in development of their overall assessment of condition and list of impaired
      waters. Discussion identified some of the technical and institutional problems
      that hinder the use of EMAP methods and data in the analysis to identify impaired
      waters as well as development needs to overcome these problems.

PMID- 15861987
TI  - Watershed-based survey designs.
AB  - Watershed-based sampling design and assessment tools help serve the multiple
      goals for water quality monitoring required under the Clean Water Act, including
      assessment of regional conditions to meet Section 305(b), identification of
      impaired water bodies or watersheds to meet Section 303(d), and development of
      empirical relationships between causes or sources of impairment and biological
      responses. Creation of GIS databases for hydrography, hydrologically corrected
      digital elevation models, and hydrologic derivatives such as watershed boundaries
      and upstream-downstream topology of subcatchments would provide a consistent
      seamless nationwide framework for these designs. The elements of a watershed
      based sample framework can be represented either as a continuous infinite set
      defined by points along a linear stream network, or as a discrete set of
      watershed polygons. Watershed-based designs can be developed with existing
      probabilistic survey methods, including the use of unequal probability weighting,
      stratification, and two-stage frames for sampling. Case studies for monitoring of
      Atlantic Coastal Plain streams, West Virginia wadeable streams, and coastal
      Oregon streams illustrate three different approaches for selecting sites for
      watershed-based survey designs.

PMID- 15861988
TI  - Selecting socio-economic metrics for watershed management.
AB  - The selection of social and economic metrics to document baseline conditions and
      analyze the dynamic relationships between ecosystems and human communities are
      important decisions for scientists, managers, and watershed citizens. A large
      variety of social and economic data is available but these have limited use
      without theoretical frameworks. In this paper, several frameworks for reviewing
      social-ecosystem relations are offered, namely social sanctions, sense of place,
      civic structure, and cultural differences. Underlying all of these frameworks are
      attitudes, beliefs, values, and norms that affect which questions are asked and
      which indicators are chosen. Much work and significant challenges remain in
      developing a standard set of spatially based socio-economic metrics for watershed
      management.

PMID- 15861989
TI  - Prophylaxis of the epilepsies: should anti-epileptic drugs be used for preventing
      seizures after acute brain injury?
AB  - In many circumstances antiepileptic drugs are used in patients who have never
      presented any clinical epileptic seizures. These substances are administered on
      the assumption of a potential risk for the patients of developing acute or
      delayed chronic seizures after brain injuries such as trauma, stroke, hemorrages
      or even neurosurgical interventions. The aim of this paper is to propose
      therapeutic guidelines for the management of this prophylactic attitude in
      epilepsy based on basic research and clinical practice in the French community in
      Belgium. We will distinguish between the prevention of acute (early onset
      provoked) seizures and a delayed truly post-lesional (unprovoked) epilepsy. Some
      therapeutic goals can be achieved under the former circumstances whereas in the
      latter situation we all agree for the absence of any coherent antiepileptic
      prophylactic behaviour.

PMID- 15861990
TI  - Guidelines for recognition and treatment of the psychoses associated with
      epilepsy.
AB  - Epilepsy and psychiatric diseases are frequent comorbidities. Psychoses in
      patients with epilepsy have special physiopathology and several clinical
      presentations and prognoses. Their treatments are also specific, according to the
      specific diagnosis. This paper represents the summary of a consensus meeting held
      in November 2003 by a Belgian French-speaking group of neurologists,
      neuropediatricians and psychiatrists and proposes guidelines for the recognition
      and treatment of those entities.

PMID- 15861991
TI  - How to approach the patient with muscular symptoms in the general neurological
      practice?
AB  - Muscle symptoms and signs are a frequent reason for general neurological
      consultations. Weakness is the most reliable clinical indicator of myopathy.
      Fatigue and exercise intolerance and myalgias frequently occur in non-myopathic
      conditions. Cramps and myoglobinuria are more often due to systemic factors than
      being a sign of a metabolic or other myopathy. Contractures and myotonia are rare
      findings but when present are strong leads towards specific myopathic diagnoses.
      Serum creatine kinase (CK) is the single most useful screening laboratory study.
      Creatine kinase increase does not only occur in myopathies, and some myopathies
      cause no CK increase. Rapid recruitment of short duration, low amplitude motor
      unit potentials is the most typical hallmark of needle electromyography in
      myopathies. Critical appreciation of the clinical, laboratory and
      electromyography findings will help general neurologists select the few patients
      that need referral for muscle biopsy and genetic studies.

PMID- 15861992
TI  - Clinical neurophysiology of dystonia.
AB  - It took decades to accept that dystonia, a bizarre condition which often produces
      abnormal movements exclusively during specific activities like writing, was due
      to brain disease. Clinical neurophysiology certainly added to this evolution of
      thinking. Recent neurophysiological observations demonstrate that dystonia is not
      only due to an isolated brain motor dysfunction, but also to sensory and
      sensorimotor integration disturbances. We hope that new treatment strategies will
      arise thanks to our better understanding of dystonia pathophysiology.

PMID- 15861993
TI  - Compensating strategies for impaired episodic memory and time orientation in a
      patient with Alzheimer's disease.
AB  - A dedicated training program for teaching a patient with Alzheimer's disease to
      independently use an agenda is presented. This training capitalises on preserved
      cognitive abilities and incorporates principles from learning theories. This case
      study reports the effective use of a memory book for daily life activities and of
      a digital clock for time reorientation.

PMID- 15861994
TI  - Gradual recovery of impaired cardiac autonomic balance within first six months
      after ischemic cerebral stroke.
AB  - BACKGROUND: The level of autonomic dysbalance in the first months after acute
      ischemic cerebral stroke has not been thoroughly investigated, and the available
      data are uncomplete. The aim of this research is to establish the degree and
      dynamics of impaired cardiac autonomic balance recovery within the first six
      months following the acute ischemic cerebral stroke. METHODS: This prospective
      study included 78 patients who had suffered the first ischemic cerebral stroke
      and 78 sex and age-matched healthy subjects. We have analyzed heart rate
      variability (HRV) from a 24-hour Holter ECG. In the group of patients with
      ischemic cerebral stroke, HRV was measured after two and six months following the
      acute phase, respectively. RESULTS: Two and six months after the acute ischemic
      cerebral stroke, all HRV variables, except low to high frequency ratio (LF/HF),
      were significantly lower in the group of stroke patients when compared to the
      control group. Furthermore, we found a significant increase in the overall HRV
      between months 2 and 6 after the acute phase of cerebral stroke; p = 0.03 for
      Standard deviation of all normal R-R intervals (SDNN) and p = 0.01 for Total
      power. CONCLUSIONS: The results point to the gradual recovery of impaired cardiac
      autonomic balance in the patients with ischemic cerebral stroke within the first
      months following the acute phase. Nevertheless, HRV remains significantly lower
      even six months after the acute phase in comparison to healthy subjects.

PMID- 15861995
TI  - A case report of an uncommon neuropathy: posterior femoral cutaneous neuropathy.
AB  - Isolated posterior femoral cutaneous neuropathy is rarely encountered.
      Electrophysiological documentation has only been made in a few cases. We present
      a 73 year-old male patient who underwent a coronary angiography procedure which
      was performed on his right femoral artery 2 months prior of referring to our
      electromyography (EMG) laboratory. After this event, he had an operation in order
      to evacuate the hematoma formed in the right inguinal region during the
      procedure. In the postoperative state he began to complain of a pain and numbness
      in his right posterior thigh; which had radiated towards his right hip and
      popliteal fossa. In addition to routine electrophysiological nerve conduction
      studies conducted in lower extremities; we performed posteriorfemoral cutaneous
      nerve conduction using the method described by Dumitru and Nelson. While normal
      response can be obtained easily on the left side; no potential could be obtained
      from the right.

PMID- 15861996
TI  - Carbamazepine induced osteomalacia: letter to the editor.

PMID- 15861997
TI  - Multiple neurological syndromes during Hodgkin lymphoma remission.
AB  - We report a young patient who developed a stiff man syndrome (SMS) long after
      remission of Hodgkin lymphoma. This patient is remarkable because he has had
      several other potentially autoimmune or paraneoplastic neurological syndromes
      including limbic encephalitis and demyelinating polyneuropathy which also
      occurred years after remission from Hodgkin disease.

PMID- 15861998
TI  - An unusual presentation of hepatocellular carcinoma: case report and review.
AB  - Hepatocellular carcinoma (HCC) is a common cancer presenting in adults with an
      increasing incidence in the United States. The many etiologies of cirrhosis place
      patients at increased risk for developing hepatocellular carcinoma but not all
      patients who develop this cancer have underlying cirrhosis. Presented is a case
      of a man without cirrhosis or any known risk factors for liver disease who was
      admitted in fulminant hepatic failure. He was found to have hepatocellular
      carcinoma complicated by an extensive tumor thrombus. At autopsy, underlying
      hemochromatosis was discovered. The etiologies, clinical manifestations,
      diagnostic modalities and treatment options are discussed patients with
      hepatocellular carcinoma.

PMID- 15861999
TI  - Change in cesarean section rate as a reflection of the present malpractice
      crisis.
AB  - OBJECTIVE: To examine the potential effect of the malpractice crisis on the
      cesarean section rates of practicing obstetricians. METHODS: We reviewed the
      medical records of primagravid women, from both clinic and private practice
      settings, having singleton deliveries at Hartford Hospital from 1994 to 2003. The
      records of cesarean sections due to fetal distress and cephalopelvic
      disproportion (CPD) were further analyzed for three different two-year periods;
      1994-1995, 1999-2000, and 2002-2003. Cases with accepted indications for elective
      cesarean sections were excluded. These included breech position, HIV, herpes,
      preeclampsia, placenta previa, and abruptio placenta. RESULTS: The private
      cesarean rate in 1994-1995 was 15.6%, 1999-2000 15.7%, and in 2002-2003 24.8%, a
      58% increase. This is a significant increase that was not equally seen in the
      clinic population during the same period. CONCLUSION: The private, primagravid
      cesarean section rate has increased significantly in the last two years. A
      concurrent rise in medical malpractice actions and malpractice insurance
      premiums, without other attributable explanations, suggests this may be a major
      factor.

PMID- 15862000
TI  - Lymphocytic hypophysitis.
AB  - Lymphocytic hypophysitis (LH) is a rare but increasingly recognized inflammatory
      disorder of the pituitary, usually associated with pregnancy. Knowledge of this
      condition is largely anecdotal; the cause, incidence, and natural history are
      unknown. Cases are usually discovered at biopsy and surgical intervention for a
      presumptive pituitary neoplasm. Here we describe two cases of lymphocytic
      hypophysitis. In the first case the patient underwent surgery for presumptive
      adenoma, and pathology at resection established the diagnosis of lymphocytic
      hypophysitis. The second case was strongly suspicious for LH by history,
      endocrine profile, and imaging, and was managed nonoperatively. Though magnetic
      resonance imaging (MRI) features are not diagnostic, knowledge of imaging
      features together with clinical history may permit avoidance of surgery.

PMID- 15862001
TI  - Principles of pain management: agents used for somatic pain.

PMID- 15862002
TI  - Smallpox prevention: Farmington, 1827, and after 9/11.

PMID- 15862003
TI  - Two sides.

PMID- 15862004
TI  - The future of the white coat.

PMID- 15862005
TI  - On the pleasures and benefits of rereading books.

PMID- 15862006
TI  - [Project summarize of "reestablishing disease prevention and control system of
      China"].
AB  - This paper introduced the project of "reestablishing the disease control and
      prevention system of China" in brief, including background, objectives, funding
      resources, researching objects and sampling methods. This project which funded by
      National Outstanding Younger Fund and the research fund of MOH aimed at nailing
      down the key problem existed in disease control and prevention system of China,
      demonstrating the reasons and mechanism of key problem, developing feasible
      policy idea and strategy. This paper also introduced some issues concerning the
      reestablishing of the disease control and prevention system of China: the
      definition of public function, the standard of human resource allocation and the
      standard of financing. The Centers for Disease Control and Prevention in 8
      provinces, 80 cities and 80 counties have been sampled to provide information
      that project needed. In addition, this project also cited some data which come
      from the early study, in which 3 provinces, 12 counties, 49 towns, 179 villages
      and 9781 rural families have been sampled and investigated.

PMID- 15862007
TI  - [Results summarize of the project of "reestablishing disease prevention and
      control system of China"].
AB  - This paper introduced the following study results of the project of
      "reestablishing the disease control and prevention system of China" in brief: (1)
      the chief problem existed in disease control and prevention system of China is
      the lower fulfilling level of public functions. (2) the parents of this chief
      problem are the lower financing level and the lower managing responsibility of
      government. (3) to reestablish the disease control and prevention system of
      China, government should increase the investment and strengthen management, which
      may need the following preconditions: more government recognitions to the disease
      control and prevention, more government investment, more sustainable government
      investment, higher efficiency of CDC, more competitive salary system to recruit
      specialists, more reliable disposal about non-public-product provided by CDC. (4)
      the public functions of CDC could be defined as 7 categories and 255 items. (5)
      according to the calculating method of human resources allocation of CDC which
      has been developed and demonstrated by the project team, 159086 persons, which is
      equal to 76.9% of human resources of CDC in 2002, are needed to fulfill all the
      public function of CDC throughout the country. (6) based on the model of input
      output analysis, to exclude the non-public-service of CDC, government should give
      another yen 10.29 billions on the basis of current 3.9 billions of government
      investment to CDC.

PMID- 15862008
TI  - [The problem of public health service delivery insufficiency of disease
      prevention and control system of China].
AB  - OBJECTIVE: To demonstrate the chief problem existed in the disease control and
      prevention system of China. METHODS: Literatures in 8 national academic journals
      concerning health service management have been reviewed. The method of boundary
      analysis has been employed to conclude the various problems existed in the
      disease prevention and control system of China. RESULTS: 205 literatures have
      been carefully reviewed and 12 kinds of problems have been concluded.
      Furthermore, 98.0% investigated CDC agreed that the insufficiency of public
      health service delivery was the chief problem existed in the disease prevention
      and control system of China. CONCLUSION: Some powerful policies should be
      developed to increase the public health service delivery of the disease
      prevention and control system of China.

PMID- 15862009
TI  - [Study on relationship between fatigue and work ability in chemistry workers].
AB  - OBJECTIVE: Explore the relationship between fatigue and work ability in 976
      chemistry workers. METHODS: A test of fatigue and work ability was carried out
      with fatigue scale and work ability index (WAI) for 976 workers, other influence
      factors of the work ability (such as work environment, labor load, job factors)
      were investigated with questionnaire. RESULTS: (1) The frequency of fatigue of
      the unmarried workers was significantly lower than that of the married workers
      and other marital status workers, while the score of WAI of the unmarried was
      significantly higher than that of those( P < 0.05); (2) the frequency of fatigue
      of the mental workers was significantly lower than that of the mixed physical and
      mental workers, while the score of WAI of the mental workers was significantly
      higher than that of physical workers and mixed physical and mental workers ( P <
      0.05); (3) compared with the workers free of fatigue, the other workers had lower
      WAI scores; (4) the fatigue score correlated negatively to the WAI score (r = 
      0.499, P < 0.01); (5) Cumulative odds model analysis showed that after
      controlling the other risk factors, fatigue was an important risk factor of work
      ability (OR = 4.005). CONCLUSIONS: Fatigue has affected work ability in chemistry
      workers, the frequency of fatigue is higher, the score of WAI is lower.

PMID- 15862010
TI  - [Study on relationship between coping resources and strain in mental workers].
AB  - OBJECTIVE: To study the effects of mental workers' coping resources on their
      strain. METHODS: Strain (vocational strain, psychological strain, interpersonal
      strain, physical strain) and coping resources (recreation, self-care, social
      support, rational coping) were measured on 3379 mental workers with personal
      strain questionnaire (PSQ) and personal resources questionnaire (PRQ). RESULTS:
      There existed significantly negative correlations between PRQ and PSQ (P < 0.01).
      In PRQ, social support (SS) and rational coping (RC) had the closest
      relationships with PSQ. In the items of SS, those related to feeling support had
      more remission on strain. In the items of RC, those related to reasonable
      arrangement of time and anti-interference had more remission on strain. In the
      items of recreation (RE), those related to self-determination had more effects on
      the remission of strain, while indulging in watching TV could cause the strength
      of strain, and there was a positive correlation between watching TV and strain (P
      < 0.01). In the items of self-care (SC), sufficient sleeping had the most effects
      on the remission of strain in the all 40 items of PRQ, while not being immersed
      in contemplation had a positive correlation with strain (P < 0.01). CONCLUSION:
      Enhancing coping resources, especially sufficient sleeping, feeling support and
      reasonable arrangement of time, were the important measures for the remission of
      mental worker' strain.

PMID- 15862011
TI  - [The immunological effects in guinea pig sensitized by trichloroethylene].
AB  - OBJECTIVE: To investigate the changes of certain immunological indexes in
      development of Guinea Pig allergic dermatitis induced by trichloroethylene (TCE).
      METHODS: The Guinea Pig model of TCE-induced allergic dermatitis was established
      by Guinea Pig Maximisation Test. IgG levels in serum were measured by sandwich
      enzyme immunoassay. The splenic T lymphocytes ConA-stimulated proliferation
      function and natural killer (NK) cell activity were detected by MTT assay and
      micro-LDH release assay, respectively. RESULTS: The sensitization rate of TCE was
      66.7%. The IgG level in serum of TCE-sensitized animals was significantly higher
      than that in normal animals (P < 0.05). No obvious differences in Splenic T
      lymphocytes proliferation index and NK cell activity between TCE-sensitized and
      normal animals were found (P > 0.05). CONCLUSION: Humoral immunity may play an
      important role in development of allergic dermatitis induced by TCE.

PMID- 15862012
TI  - [Effect of sulphamethazine on the gene expression of FRTL-5 cells].
AB  - OBJECTIVE: To study the effect of Sulphamethazine on the gene expression of FRTL
      5 cells, and to explore the mechaniams of environmental thyroid hormone
      disruptors. METHODS: cDNA microarray technique was used to analyze the gene
      expression of FRTL-5 cells of exponential phase treated by 2.0 microg/ml
      Sulphamethazine for 24 h. Total RNA from treated and untreated cells were labeled
      by Cy3 dCTP and Cy5 dCTP respectively. The ratios of Cy3/Cy5 were calculated in
      order to find the genes which expressed differently. RESULTS: There were 679
      genes (approximately 7%, total 9753 genes) exhibiting different expression, in
      which 395 (4.0%) genes up-regulated and 284 (3.0%) genes down-regulated. These
      genes related to regulation of gene expression, regulation of cell cycle,
      metabolism in cells, and so on. CONCLUSION: The effect of Sulphamethazine on FRTL
      5 cells may be related with a series of genes.

PMID- 15862013
TI  - [Detection of DNA damages of peripheral white blood cells in benzene-exposed
      workers].
AB  - OBJECTIVE: To investigate the effect of benzene exposure on DNA damage of the
      peripheral white blood cells and to assess the possible dose-response
      relationship between benzene and DNA damage. METHODS: Personal benzene exposure
      was sampled with 3M organic vapor monitors. The time weighted average
      concentration (8h-TWA) and the cumulative dose were calculated. Single cell gel
      electrophoresis assay was used to detect DNA damage in white blood cells of
      benzene-exposed workers. The Olive tail moment and the grade of DNA breakage were
      used to measure DNA damage. RESULTS: The Olive tail moment and the grade of DNA
      breakage in benzene exposure groups were significantly increased in comparison
      with those in the control group (F = 30.03, P < 0.0001, chi2 = 239.9, P < 0.0001,
      respectively) and showed a dose-response relationship with benzene concentration.
      Correlation analysis showed that Olive tail moment was correlated with benzene
      exposure concentration. CONCLUSIONS: Benzene exposure resulted in an increase of
      DNA damage of the peripheral white blood cell, which was in a dose-response
      relationship manner; cumulative dose was better than simply concentration to
      reflect benzene exposure.

PMID- 15862014
TI  - [Automatic analysis of micronuclei by flow cytometry using anti-CD71-FITC and PI
      staining].
AB  - OBJECTIVE: To explore flow cytometry (FCM) based method for automatic analysis of
      micronuclei (MN) in cells staining with anti-CD71-FITC and PI. METHODS: Cell were
      fixed in -85 degrees C methanol and stained with anti-CD71-FITC and PI,
      instrument was optimized using malaria-infected erythrocytes as biological
      standards, a FCM based method for automatic analysis of micronuclei was
      established. In order to estimate the reliability of the method, the frequencies
      of micronucleated reticulocytes (MN-RET) in peripheral blood of NIH mice treated
      with colchicine (COL) was detected using the method. RESULTS: Four cell
      populations, normochromatic erythrocytes (NCE), reticulocytes (RET),
      micronucleated erythrocytes (MN-NCE) and MN-RET could be clearly resolved on the
      FL1-FL2 dot plot using this method. COL induced a dose-dependent increases in the
      frequency MN-RET in peripheral blood. Data obtained manually and automatically
      showed a strong linear correlation (r = 0.98) as far as the percentage of MN-RET.
      CONCLUSIONS: The FCM-based automatic technique using FITC-anti-CD71 and PI
      staining is a reliable tool for micronucleus analysis.

PMID- 15862015
TI  - [The effect of high dose fluoride on the rat offspring osteoblasts which ingested
      by female rats].
AB  - OBJECTIVE: To investigate the effect of high dose fluoride which ingested by
      female rats on morphologic change in rat offspring's bone and osteoblast, discuss
      the relation between the mechanism of fluorosis and cell cycle, cell apoptosis.
      METHODS: In stock diets condition, Wistar female rats drank distilled water
      containing 0,50,100,150 mg/L NaF for 2 months, then they are mated with normal
      rats. The calvarium and osteoblast of offsprings were used to investigate the
      effects of fluoride on ultrastructure by LM and TEM. FCM was used to analysis
      cell cycle and apoptosis. RESULTS: The Electron microscope revealed the number of
      microvilli of osteoblasts were overall decreased in rat offsprings with
      fluorosis. There was mitochondrial swelling and dilation of the rough endoplasmic
      reticulum (RER). The matrix of calvarium was hyperplasia and collagen was
      accumulated and turbulenced. The nuclear manifested the apoptosis character. NaF
      at 150 mg/ L increased the osteoblast number of S phase with relative decrease of
      cell number of G2/M phase, but did not change that in G0/G1 phase. The apoptosis
      percentage increased in this group. CONCLUSION: Excessive fluoride can directly
      through the placental barrier, influence cell structure and cell cycle
      distribution of fluorosis rat offspring and render the cell cycle stagnant in S
      phase, induce apoptosis.

PMID- 15862016
TI  - [Relationship between spermatogenic cell apoptosis and serum estradiol level in
      rats exposed to fluoride].
AB  - OBJECTIVE: To observe the relationship between spermatogenic cell apoptosis and
      serum estradiol level in rats exposed to fluoride. METHODS: A total of 30 male
      Wistar rats were allocated into six groups randomly. The six experimental groups
      were 28-day control group, 28-day low-dose fluoride treatment group, 28-day high
      dose fluoride treatment group, 38-day control group, 38-day low-dose fluoride
      treatment group, and 38-day high-dose fluoride treatment group. The fluorosis
      model was acquired by subcutaneous injection of NaF solution. The content of NaF
      in testis was measured by using fluorine selective electrode. The serum estradiol
      level was radioimmunochemically detected. And the apoptotic spermatogenic cells
      were quantitatively measured by TUNEL. RESULTS: The content of NaF in testis and
      the ratio of apoptotic spermatogenic cell in fluoride treatment groups
      significantly increased with increased experimental dosage and prolonged
      experimental period (P < 0.05). Meanwhile, the serum estradiol level
      significantly decreased (P < 0.05), which was negatively correlated with the
      content of NaF in testis as well as the ratio of apoptotic spermatogenic cell (P
      < 0.05). CONCLUSION: Excessive fluoride could lead disturbance to serum estradiol
      level during some range of dose and time, which is an important factor to
      spermatogenic cell apoptosis.

PMID- 15862017
TI  - [Effect of fluoride on activities of enzyme and ultrastructure in primary
      cultured rat hepatocytes].
AB  - OBJECTIVE: To study the cell viability, activities of enzyme and ultrastructure
      changes induced by sodium fluoride in primary cultured rat hepatocytes. METHODS:
      Hepatocytes were isolated using half-in situ collagenase digestion method.
      Cellular viability was determined by MTT method. The activities of ALT and AST
      were determined by spectrophotography method. The ultrastructure changes of
      hepatocyte were observed under transmission electron microscope. RESULTS: After
      cultured with various concentrations of fluoride for 24 hours, a dose-dependent
      decrease of cell viability was detected in the hepatocytes. The activities of AST
      and ALT in the 2 mmol/L and 4 mmol/L groups were significantly higher than the
      control group (P < 0.05). Transmission electron microscope study showed that in
      fluoride treated hepatocytes the changes included swollen mitochondria and
      disordered, disrupted endoplasm reticulum. CONCLUSION: Excessive fluoride induced
      significant toxicity in primary cultured hepatocytes which manifested the
      injuries of membrane and organell plasma membrane.

PMID- 15862018
TI  - [Effects of perfluorooctane sulfonate on spermiogenesis function of male rats].
AB  - OBJECTIVE: To evaluate the effects of administration of perfluorooctane
      sulfonate(PFOS) on spermiogenesis function of male rats. METHODS: 36 male rats
      were randomly divided into 4 groups, which received 0, 0.5, 1.5, 4.5 mg x kg(-1)
      PFOS by food intake per day for 65 days. The testicular and epididymal viscera
      coefficients, the number, motility and deformity of sperm were examined. The
      activities of lactate dehydrogenase isoenzyme-x (LDHx), sorbitol dehydrogenase
      (SDH) and the generation of malonyldialdehyde (MDA) in the testes were also
      measured. RESULTS: The viscera coefficients did not show any significant change (
      P > 0.05) while the body weight and weight of testis decreased ( P < 0.05) in
      treated rats compared with the corresponding control group animals. In 1.5,4.5 mg
      x kg(-1) PFOS treated rats there were significant decreases in the sperm count (P
      < 0.05) and the mean activities of LDHx and SDH whereas obvious increases in the
      rate of sperm deformity ( P < 0.05). In 4.5 mg x kg(-1) PFOS group the generation
      of MDA increased (P < 0.05) while the motility of sperm reduced (P < 0.05) with
      respect to the control value. CONCLUSION: It suggested that PFOS could elicit the
      impairment of sperm production and maturation of male rats.

PMID- 15862019
TI  - [The immediate early genes expression in the PC12 cells activated by anatoxin-a].
AB  - OBJECTIVE: To explore the regulative action of IEGs when the nicotinic
      acetylcholine receptors (nAChRs) of PC12 cells were activated by anatoxin-a.
      METHODS: Using the reverse transcription polymerase chain reaction (RT-PCR)
      method, the mRNA gene expression of c-fos, c-jun, NGFI-A and NGFI-B were measured
      while PC12 cells were activated by anatoxin-a. RESULTS: As 10(-9), 10(-8) and 10(
      7) mol/L anatoxin-a activated PC12 cells for an hour, or 10(-7) mol/ L anatoxin-a
      activated PC12 cells for 30 min, 60 min, 120 min, the intracellular gene
      expression of c-fos and NGFI-A increased significantly than the control group (P
      < 0.05), it was 2-6 times than the control group. And the gene expression of c
      fos presented dose-response and time-effect relation. However, under the same
      condition, the gene expression of c-jun and NGFI-B did not show any remarkable
      changes. CONCLUSION: c-fos and NGFI-A might be involved to modulation the action
      of anatoxin-a activating the nAChRs of PC12 cells.

PMID- 15862020
TI  - [Effects of electromagnetic radiation in metropolis environment on teenagers'
      electrocardiogram and blood cells].
AB  - OBJECTIVE: Our previous investigation indicated that electromagnetic radiation
      level of city environment in some frequency range has gotten close to national
      standard limits. This study is to investigate the effects of these frequency
      electromagnetic waves coexisted in same environment on teenagers'
      electrocardiogram and blood cells. METHODS: Electrocardiogram and blood cells
      were examined in 106 cases of teenagers by using electrocardiograph and blood
      counting instruments respectively. RESULTS: There were not significantly
      different in heart rate, P-R interphase, QRS-wave time, Q-T interphase, blood
      hemoglobin content and blood platelet number in teenagers between high and low
      electromagnetic radiation environment (P > 0.05). The total blood leucocyte
      number in teenagers was statistically lower in high electromagnetic radiation
      environment than that in low electromagnetic radiation environment (P < 0.05).
      With regard to classification of blood leucocyte, the blood monocyte number in 14
      - 18 years old of teenagers and the blood eosinophil number in boy were
      significantly higher in high electromagnetic radiation environment than those in
      low electromagnetic radiationenvironment (P < 0.05). CONCLUSION: The
      electromagnetic radiation nowadays in metropolis environment may have no harmful
      effects on teenagers' electrocardiogram and have harmful effects on teenagers'
      blood leucocyte-mainly showing decreased total blood leucocyte number, increased
      percentages of monocyte and eosinophil number.

PMID- 15862021
TI  - [Oxidative stress induced by NaAsO2 in HaCaT cells].
AB  - OBJECTIVE: To study the level of oxidative stress induced by sodium arsenite
      (NaAsO2) in HaCaT cells. METHODS: The AlamarBlue assay was used to evaluate the
      viability of HaCaT. The level of ROS was detected by staining. cells with DCFH
      DA. The contents of reduced (GSH) and oxidated (GSSG) glutathione were detected
      with the fluorescent method. The apoptosis and necrosis rates were counted based
      on the PI staining. RESULTS: The reduction of AlamarBlue increased in the cells
      treated at dose of 0.001 -1 micromol/L NaAsO2 and decreased in the cells treated
      at doses of over 10 micromol/L NaAsO2. The fluorescent density of DCF
      significantly increased in all experimental groups, the contents of GSH and GSSG
      increased in groups higher than that of 1 micromol/L and higher than that of 5
      micromol/L respectively. The apoptosis and necrosis rates were increased markedly
      at dose of 20 micromol/L. CONCLUSION: Arsenic could induce enhancive ROS in
      HaCaT. At low levels of arsenic the proliferation of HaCaT was stimulated while
      at high levels of arsenic was inhibited. The increase in contents of GSH and GSSG
      could be associated with the excessive ROS and with detoxification in HaCaT.

PMID- 15862022
TI  - [Experiment study on the estrogen-like effect of compounds of mercury, chromium
      and manganese].
AB  - OBJECTIVE: In order to study estrogen-like effect of compounds of Mercury,
      Chromium and Manganese. METHODS: Mercury Chloride, Manganese Sulfate, Chromium
      Chloride and Chromium trioxide were selected to perform proliferation assay of
      MCF-7 human breast cancer cells and binding assay of estrogen receptor for rat
      uterine. RESULTS: Mercury Chloride could stimulate the proliferation of MCF-7
      cell, the maximal increase of MCF-7 cells was measured by Mercury Chloride at 10(
      7) mol/L. The effect was blocked completely by a pure antigestrogen ICI182, 780;
      but Mercury Chloride could not bind to ER by competing with E2. Chromium
      Chloride, Chromium Trioxide and Manganese Sulfate were not able to stimulate the
      proliferation of MCF-7 cell and bind to ER through competing against 3H-E2 in
      vitro. CONCLUSION: Mercury Chloride exhibited the estrogenicity through binding
      and activating ER; Chromium Chloride, Chromium trioxide and Manganese Sulfate did
      not show any estrogenicity.

PMID- 15862023
TI  - [A correlative study on heterotrophic bacteria and the main pollutant in city
      lakes' water].
AB  - OBJECTIVE: To provide scientific basis for bioremediation of city lake, the
      distribution of heterotrophic bacteria and its correlation with major pollutions
      condition were studied. METHODS: Puping Lake and Moshui Lake of Wu Han City were
      choosen as the objects of our study. COD(cr) TOC, TP and TN were determined in
      sampled freshwater and sediment via the standard methods. At the same time the
      bacteria was cultivated. RESULTS: The average value of COD(cr), TOC, TP and TN
      were 8. 934 mg/L, 5.125 mg/L, 0.089 mg/L, 4.739 mg/L in Puping Lake and 86.296
      mg/L,13.255 mg/ L, 1.796 mg/L, 7.325 mg/L in Moshui Lake. Ten strains of
      heterotrophic bacteria were isolated from the sample and they are Pseudomonas,
      Bacillus, Enterobateriaceae, Aeromonas and Coccus. The dominant strain in water
      was Pseudomonas. The proportion of Bacillus in sediment was relatively higher. In
      the two lakes, the average bacteria counts were 1.90 x 10(3) CFU and 5.53 x 10(4)
      CFU per mL in water, 3.12 x 10(5) CFU and 5.06 x 10(5) CFU per g in sediment.
      CONCLUSION: Puping Lake and Moshui Lake were polluted seriously according to the
      standard; Gram negative rods were the main types in water, and the dominant type
      was Pseudomonas, the Gram positive bacteria was Bacillus; The type and quantity
      of bacteria in Moshui Lake were higher than those in Puping Lake, and there were
      correlations between the quantity of bacteria and the pollutants.

PMID- 15862024
TI  - [Effects of volatile organic compounds inhalation on the inflammation biomarkers
      in nasal lavage fluids of decoration workers].
AB  - OBJECTIVE: To study the effects of volatile organic compounds (VOCs) inhalation
      on the inflammation biomarkers in nasal lavage fluid (NAL), and to assess the
      practicability of the nasal lavage methods. METHODS: 32 volunteers joined in this
      study, among whom 20 Painters were chosen as exposed group, and 12 plumbers and
      electricians were chosen as controls. Lung function was detected, and several
      inflammation biomarkers (IL-4, IL-5, ECP) in nasal lavage (NAL) were determined.
      RESULTS: The average FEV1 of exposed group was 3.08L, which was significantly
      lower than the control. And the concentration levels of inflammation biomarkers
      in NAL of painters were higher than that of the control. Among these detected
      biomarkers, the ECP level was significantly higher in exposed group than in
      control group(the mean was 3.57 microg/L in painter and 2.79 microg/L in the
      control, respectively). Moreover, there was statistically negative correlation
      between ECP level and FEV1 (a kind of lung function parameters), the correlated
      coefficient was -0.381. CONCLUSION: Inhalation of VOCs could be responsible for
      the occurrence of respiratory inflammation and allergic illness such as rhinitis
      and asthma. Moreover, the method of nasal lavage is practicable for population
      study.

PMID- 15862025
TI  - [Roles of mitochondria in vitamin E succinate-induced apoptosis in human gastric
      cancer SGC-7901 cells].
AB  - OBJECTIVE: In order to investigate the roles of mitochondria in vitamin E
      succinate (VES)-induced apoptosis in human gastric cancer SGC-7901 cells.
      METHODS: Mitochondrial transmembrane potential (deltapsi(m)) was observed by
      confocal laser scanning microscopy, while the expression of cytochrome c in
      cytosol and caspase-3 was measured by western blotting after the cells were
      treated with VES at 5, 10, 20 microg/ml. RESULTS: VES obviously decreased
      deltapsi(m) with dose- and time-dependent relationship, increased the expression
      of cytochrome c in cytosol and caspase-3 and activated caspase-3 as well.
      CONCLUSION: VES-induced apoptosis in SGC-7901 cells might involve mitochondrial
      permeability transition, release of cytochrome c and activation of caspase-3
      downstream.

PMID- 15862026
TI  - [Effect of alcohol on brain mitochondria development of mouse embryos].
AB  - OBJECTIVE: To probe the effect of alcohol consumption on brain mitochondria
      development of mouse embryos. METHODS: Pregnant mice were given alcohol
      intragastrically from pregnant day (PD) 6 - 5. On PD 18, embryos were dissected
      out and the brain mitochondria were extracted. Then mitochondria membrane
      potential, activities of mitochondria respiratory chain complex I, IV and ATPase,
      and ATP content were measured in vitro. RESULTS: The ratio of fetal brain/body
      weight decreased as the maternal alcohol dosage increasing. An increased
      proportion of immature mitochondria, from 18 percent to 34 percent, was detected
      by flow cytometry. Reduced activities of respiratory chain complexes I and IV
      were found in 3.0 g/kg/day (91.7% and 87.9% respectively) and 6.0 g/kg/day
      alcohol exposure groups (72.4% and 69.7% respectively). Only 6.0 g/kg/day ethanol
      exposure group showed significantly reduced activity (80.3% of control) of
      ATPase. ATP contents in the fetal brain mitochondria of 3.0 g/kg/day and 6.0
      g/kg/day maternal alcohol exposure groups were significantly less than that of
      control, implying an impaired mechanism of ATP synthesis and/ or uptake.
      CONCLUSION: Alcohol consumption during pregnancy can affect embryo brain
      mitochondria development, which may be related to the neural tube defects induced
      by alcohol.

PMID- 15862027
TI  - [Regulatory effects of micronutrient complex on the expression of Th1 and Th2
      cytokines in diabetic C57BL mice].
AB  - OBJECTIVE: To investigate the regulatory effects of micronutrients complex (MC)
      on the expression of Th1 and Th2 cytokines in diabetic mice for exploring the
      molecular mechanisms of MC in treating for diabetes. METHODS: IDDM mice model was
      made by the injection of multiple low dose of streptozotocin (MLDS). The
      composition of Selenium (Se), Vitamin E (VE), Vanadium (V) and Chrome (Cr) was
      supplemented. The percentage of Th1 cytokines(TNF-alpha, IFN-gamma) and Th2
      cytokines (IL-4, IL-10) positive lymphocytes were detected by flow cytometer
      (FCM). RESULTS: The expression of TNF-alpha and IFN-gamma of peripheral blood
      lymphocytes of MLDS group significantly increased (P < 0.01), while the IL-10
      expression of blood and spleen lymphocytes of MLDS group obviously decreased (P <
      0.01). Combined supplementation of MC markedly decreased blood lymphocytes TNF
      alpha expression (P < 0.01) and increased blood lymphocytes IL-10 expression (P <
      0.01) and spleen lymphocytes IL-4 expression (P < 0.05) of IDDM mice
      respectively. CONCLUSION: MC may prevent from the onset and development of IDDM
      by down-regulating Th1 cytokines genes expression and up-regulating Th2 cytokines
      genes expression of IDDM mice.

PMID- 15862028
TI  - [Effect of apoptosis in human breast cancer cells and its probable mechanisms by
      genistein].
AB  - OBJECTIVE: To investigate the effects of genistein on human breast cancer cell
      MCF-7 apoptosis and its probable mechanisms. METHODS: In this study, the methods
      of MTT, cell apoptosis detecting in fluorescent and electronic microscope and
      flow cytometry, and expression of Bax and erbB-2 protein were employed. RESULTS:
      The results showed that genistein could significantly inhibit the growth and
      induce the apoptosis of MCF-7 cells. Apoptotic cells of morphology from MCF-7
      cells treated by different concentrations of genistein were observed by
      fluorescent and electronic microscope and the frequency of apoptosis in MCF-7
      cells by flow cytometry showed increasingly with concentrations of genistein
      increased. The expression of Bax protein in MCF-7 cells was increased and the
      expression of erbB-2 protein was decreased with the doses of genistein.
      CONCLUSION: Genistein can induce MCF-7 cells apoptosis and it may be one of the
      mechanisms for the inhibitory effect of genistein in human cancer cells.

PMID- 15862029
TI  - [Protective effects of Lovastatin on early diabetic renal tissue and the possible
      mechanism].
AB  - OBJECTIVE: To investigate the protective effects of Lovastatin on renal function
      in experimental diabetic nephropathy in rats. and the function of cAMP-responsive
      element binding protein (CREB1) in this duration. METHODS: Diabetes was induced
      in male Wistar rats by intrapetitoneal injection of STZ (65 mg/kg). Three groups
      were divided as: Sham group, diabetic control group and Lovastatin treatment
      group. Lovastatin (20 mg/kg) was administered daily by gavage from the next day
      of the induction diabetes for 4 weeks. Upro, ucr in urine and Glu, Scr, BUN in
      serum were determined. Immunohistochemistry and computer image-pattern analysis
      system were used to analyze expression of PCNA and p-CREB1. Western blot were
      performed to valuate the expression of p-CREB1 with their specific corresponding
      antibodies. CREB1 mRNA was measured by RT-PCR. RESULTS: After Lovastatin
      treatment, renal function were ameliorative in diabetic rats. Decrements were
      also found in the expression of and PCNA, p-CREB1 and its mRNA in the treatment
      group compared with the diabetic group. CONCLUSION: Inhibition of glomerular cAMP
      responsive element binding protein 1 may be responsible for the Lovastatin
      protective function that allevate the renal proliferation and hypertrophy in
      diabetic rats.

PMID- 15862031
TI  - [Twin study of free insulin-like growth factor-1 on female pubertal development].
AB  - OBJECTIVE: To explore the effect of insulin-like growth factor-1 (IGF-1) on
      female pubertal development and estimate heritability of the serum free IGF-1.
      METHODS: The study population consisted of 427 girls aged 6 to 18 years: 132
      pairs monozygotic twins, 48 pairs same-sex dizygotic twins and 67 girls with
      opposite-sex twin, who were all from Qingdao city, Shan-dong province. Their
      breast development were examined by Tanner standard and fast serum free IGF-1
      contents were assayed by immunoradiometric assay (IRMA). RESULTS: Serum free IGF
      1 concentration increased firstly and decreased later throughout puberty. The
      peak of free IGF-1 was 12 years old, which equals to Tanner B2. Free IGF-1
      heritability of group stage B1, B2-B5, pre-menarche and post-menarche were 0.53,
      0.85, 0.48, 0.83 respectively, non-classed heritability was 0.53. CONCLUSION:
      Fast increase of serum free IGF-1 before 12 years might be a predictor of the
      growth spurt and breast development. Genetic effect on female serum free IGF-1
      was significant in the process of puberty.

PMID- 15862030
TI  - [Effects of tea polyphenols and tea pigments on apoptosis in HepG2 cell line].
AB  - OBJECTIVE: To investigate the effect of tea polyphenols and tea pigments on
      apoptosis in HepG2 cells. METHODS: HepG2 cells were seeded at a density of 5 x
      10(5)/well in six-well culture dishes. The cells were then treated with 50 or 100
      mg/L tea pigments and harvested at 48h by trypsinization. Agrose electrophoresis
      was applied to investigate DNA-LADDER, Bcl-2 and Bax protein expression were
      detected by Western blot. RESULTS: Tea polyphenols and tea pigments induced the
      appearance of DNA-LADDER; Western blot analysis demonstrated that Bcl-2
      expression was significantly inhibited and the expression of Bax was
      significantly induced by tea polyphenols and tea pigments. CONCLUSION: Induction
      of apoptosis may be an important mechanism of cancer chemoprevention by tea.

PMID- 15862032
TI  - [Study of Qingciguo oil's function on blood lipid and other functions].
AB  - OBJECTIVE: To study Qingciguo Oil's function on blood lipid and other functions.
      METHODS: 84 male SD rats were randomly divided into seven groups (control group,
      high lipid group, low dose group, middle dose group, high dose group, combined
      dose group and combined control group) based on the level of TC. We respectively
      feed each group of rats with the normal food, high lipid high cholesterol food,
      Qingciguo Oil's 4 ml/kg BW food, Qingciguo Oil's 8 ml/kg BW food, Qingciguo Oil's
      12 ml/kg BW food, Qingciguo Oil's 12 ml/kg BW + 0.8% soybean PL + 0.05% VitE food
      & 0.8% soybean PL + 0.05% VitE food ninth week. RESULTS: At the fourth week, the
      TC of each group rats (except lower dose group) began to decreasing, and at sixth
      week, the TC of middle dose group was significantly lower than the high lipid
      group. At sixth week, the TG of low, middle and high dose group was significantly
      lower than the TG of high lipid group, the HDL of high lipid group and middle
      dose group decreased significantly, and the HDL of combined control dose group
      significantly higher than high lipid group. At the ninth week, the level of SOD
      of all experimental groups significantly higher than the high lipid group and the
      MDA of each group have no significant differents between each other. In vitro, we
      test the effect of different dose Qingciguo oil and fish oil on platelet
      aggragation of each blood by tuibidimetry, the results show that the platelet
      aggregation of Qingciguo oil high dose group was significantly lower than the
      control group. CONCLUSION: Under our condition, Qingciguo oil has certain
      functions of decreasing the level of blood lipids modulating the function of
      antioxidants and restraining the platelet aggregation in vitro.

PMID- 15862033
TI  - [Study of mechanism on immune response in goats by different immunization with
      Helicobacter pylori and analyse of its prospects for using].
AB  - OBJECTIVES: To observe the effect of three different routes on the induction of
      immunogenicity to whole bacterial antigen of Vac A+ Helicobacter pylori strain
      (NCTC11637) and explore its mechanism. METHODS: Two milk goats and one pregnant
      goat were immunized by different routes respectively with whole bacterial of H.
      pylori (6 x 10(9) cfu/ml) cultivated by solid culture medium. At the 1st, 14th,
      21st, 28th day, two goats were immunized four times by intranasal or subcutaneous
      injection. The other pregnant goat was immunized four times at a interval of two
      weeks before and after one month of lamb birth by muscular injection. Serum and
      milk samples were collected and assayed by indirect enayme-linked immunosorbent
      assay (ELISA). The levels of anti-Hp of IgG and IgA in serum and milk were
      determined by reading the optical density (A). RESULTS: Three immune routes all
      induced systemic immune response. The optical density (A) of ELISA proved that
      the specific IgG in serum increased while IgA didn't increase significantly, and
      that the specific IgA and IgG in milk all increased to a greater or lesser extent
      compared with control group. CONCLUSION: Three immune routes all induce systemic
      immune response, resulting in increases of anti-Hp of IgG/IgA in milk and IgG in
      serum. Among them, intranasal inoculation can induce systemic immune response and
      local immune response in different mucosal sites, which may be a safe and
      effective immunization route.

PMID- 15862034
TI  - [Influence of resistant starch on colon flora of rats].
AB  - OBJECTIVE: To investigate the effect of resistant starch (RS2 and RS3) intake on
      colon flora of mice METHODS: 32 mice were divided into four groups (8 mice/group)
      according to their weight randomly. Four groups of mice were given basic feed
      (containing only corn starch and no RS), containing 6% RS2 feed, containing 12%
      RS2 feed, and containing 6% RS3 feed, respectively. Feces were collected on the
      1st and 29th day of the experiment, and pH of feces were measured and five feces
      flora (enterobacter, bifidobacteria, lactobacillus, bacteroid, and enterococcus)
      were detected with culture medium method. All the mice were killed on the 29th
      day to get caecum content. The pH of caecum content were measured and short chain
      fatty acid (SCFA) were detected with gas chromatography. RESULTS: RS2 and RS3
      could all increase feces bifidobacteria (P < 0.05) and decrease enterobacteria (P
      < 0.05). RS2 could increase SCFA of ceacum content, and 12% RS2 group is more
      than control group (P < 0.01), and also more than 6% RS2 group (P < 0.05). RS
      could also decrease pH of feces and ceacum content of mice, and the effect of RS3
      is more than RS2. CONCLUSION: Resistant starch could improve colon flora,
      increase its fermentable production SCFA, decrease caecum and feces pH, and then
      improve health.

PMID- 15862035
TI  - [Effects of chromium supplementation on IRS-1 expression of skeletal muscle in
      diabetic rats].
AB  - OBJECTIVE: To study the effects of chromium supplementation on related gene
      expression to metabolism of skeletal muscles in diabetic rats. METHODS: cDNA
      fragments from the out related research were cloned, sequenced and its
      comparalarity analysis has been done. The RT-PCR were made using the primers
      designed according to the sequence of cDNA. RESULTS: The identities between the
      sequence of Cr-5 and IRS-1 is 100%. The expression level of DM group (0.791 +/-
      0.038) is obviously lower than those of normal group (0.892 +/- 0.053, P < 0.05).
      And The expression level of DM + Cr group (0.822 +/- 0.066) have some improvement
      compare to those of DM group (P > 0.05). CONCLUSION: There is a tendency that
      Chromium supplementation can increase the expression level of IRS-1 mRNA of
      skeletal muscles in diabetic rats. It will be studied as a candidate gene in
      future research.

PMID- 15862036
TI  - [Analysis of paralytic shellfish poison of bivalves in seafood market in
      Guangzhou].
AB  - OBJECTIVE: The investigations of the paralytic shellfish poisoning (PSP) from
      Huangsha seafood market of Guangzhou was performed to assess the risk of PSP in
      bivalves. METHODS: The concentration and profiles of PSP toxins in bivalves were
      determined by mouse bioassay of AOAC and high-performance liquid chromatography
      (HPLC). The risk assessment of PSP in bivalves was conducted with FAO and Chinese
      Administration Organization of Fish Culture and Seaport. RESULTS: The content of
      PSP detected was lower than the safe standard (4 MU/g meat) in all of the 84
      samples, one of which had the highest toxicity with 1.84 MU/g muscle. These
      results suggested that the bivalves in seafood market was safe to feed. It was 9
      samples' gland in 2 species that be detected to have PSP in the bivalves being
      researched, the muscles had few PSP. The concentration of PSP in one sample's
      gland exceeded the threshold of FAO (4 MU/g) with 14.52 MU/g meat, and the
      profiles of PSP in the gland were B1, GTX2/3, GTX1/4 and C according to HPLC.
      CONCLUSION: These results suggested that both of the concentration and detection
      rate of PSP of bivalves in seafood market in Guangzhou were low as a whole, but
      the content and discovery rate of PSP were far higher in glands than in the
      muscles, and the PSP content in one gland exceeded the threshold of Standard. The
      levels of PSP contamination in shellfish was characteristic of season. The toxins
      level in shellfish were the maximum in spring, but the frequency of toxins
      detected in shellfish was higher in summer and autumn, so the detection and risk
      assessment of PSP in bivalves from seafood market was essential in the future.

PMID- 15862037
TI  - [Effects of selenoprotein on blood glucose, Ca2+ transfer and NO system in
      diabetic mice].
AB  - OBJECTIVE: To study the controlling effect of selenoprotein on blood glucose,
      Ca2+ transfer and NO system in diabetic mice. METHODS: Male Kunming mice of (20.3
      +/- 1.7) g body weight were injected 200 mg/kg bw, 2% alloxan in abdomen to make
      diabetic model (DM), and were randomly divided into six groups: normal control
      group (I), normal + selenoprotein group(Se 100 microg/kg bw) (lI), DM control
      group (III), DM + lower dose selenoprotein group(Se 100 microg/kg bw) (IV), DM +
      higher dose selenoprotein group (Se 300 microg/kg bw) (V), DM + Na2SeO3 group (Se
      100 microg/kg bw) (VI). RESULTS: The level of blood glucose in V group [(20.4 +/-
      6.3 mmol/L] were significantly lower than lII group(45.3 +/- 3.3) mmol/L P <
      0.05. The activity of Ca(2+) -ATPase of kidney in V group (0.90 +/- 0.5 micromol/
      (h x mg prot) is significantly higher than III group [(0.35 +/- 0.1) micromol/(h
      x mg prot)] (P < 0.05, and the activity of NOS in V group [(25.0 +/- 4.3) U/ml]
      is significantly lower than III group [(35.2 +/- 4.4) U/ml] (P < 0.05).
      CONCLUSION: Selenoprotein that supplemented selenium doseis 300 microg Se/kg
      weight could significantly decrease blood glucose, increase the activities of
      Ca(2+) -ATPase on kidney and weaken the activities of plasma NOS in diabetic
      mice.

PMID- 15862038
TI  - [Study of drug poisoning on 2612 cases in the department of emergency].
AB  - OBJECTIVE: To analyze the characteristics of the drug poisoning. METHODS: In the
      25 department of emergency selected hospitals, design questionnaires to register
      the drug poisoning patients who seeking emergency treatment within one-year
      period. RESULTS: Collected 2 612 cases of drug poisoning patients, accounted as
      0.31% of the aggregated number of emergency patients at the same time, as well as
      23.42% of poisoning patients at the same time. The sexual proportion between
      males and females was 1:3.45, average age was 30.33 years, and the age groups
      between 15-34 years were the high potentials. The three top ranking industries
      were farmers, unemployed ones and services. Amongst the samples, 99.12% of them
      were exposed by mouth transmission. 84.57% were committed as suicides. The
      medicines most frequently adopted were 1. antianxity drugs; 2. analgesics
      antipyretic and antirheumatic drugs; 3. antipsychotropic drugs. Only 1.68% of the
      drug poisoning patients were diagnosed through blood-medicine. CONCLUSION: It is
      recommended to enhance the administration and education of medicines. To
      establish monitoring system for drug intoxication and improve the quality of
      diagnose and treatment of drug poisoning patients.

PMID- 15862039
TI  - [Effect of dietary n-6/n-3 polyunsaturated fatty acid ratio on spleen
      lymphocyte's function and fatty acid composition in mice].
AB  - OBJECTIVE: To study the effect of dietary n-6/n-3 PUFA ratio on spleen
      lymphocyte's function and fatty acid composition in mice. METHODS: Male BALb/c
      mice were divided into 5 groups: the dietary S : m : p was 1 : 1.5 : 1 n-6/ n-3
      PUFA ratio was 1, 7.5, 15, 30 respectively, and in the control group, dietary S :
      M : P was 1 : 1.5 : 3.7, which was followed the AIN-93G formulation. All groups
      consumed purified diet based on the AIN-93G formulation. The different n-6/ n-3
      PUFA ratios in diets were varied by mixing of oils. After 12 wks breeding, all
      mice were sacrificed, and the function and fatty acid composition of Lymphocyte,
      IL-2 and PGE2 concentration were measured. RESULTS: When dietary n-6/n-3 PUFA
      ratio approximated 1, the lymphocyte proliferation, proportions of CD4+ and CD8+
      T cell, IL-2 and PGE2 concentration decreased significantly. The concentration of
      C18 : 2, C20 : 4, n-6 PUFA in lymphocyte decreased significantly; Meanwhile, the
      concentration of C22 : 6, C16 : 1, C18 : 1 and total MUFA in lymphocyte
      significantly higher than other groups. The concentration of C2 : 6 in
      lymphocytes were significantly negative correlated with the proliferation of
      spleen lymphocytes. The concentration of C20 : 5 in lymphocyte was significantly
      negative correlated with the proportions of CD4+ T cell and IL-2 level. The
      concentration of C16 : 1 in lymphocyte was significantly negative correlated with
      the proportions of CD4+ and CD8+ T cell. CONCLUSION: The fatty acid composition
      of diet affected that of lymphocyte in mice. Compared with the T lymphocyte
      function in diet with n-6/n-3 ratio approximated 30, the T lymphocyte function in
      mice was suppressed when dietary n-6/n-3 ratio approximated 1.

PMID- 15862040
TI  - [Apolipoproptein E-CI-CII gene cluster and its effect on serum lipid levels].
AB  - OBJECTIVE: To investigate the allele frequencies of the apolipoprotein (apo)E-CI
      CII cluster gene in Hans of Chinese, and its relation to serum lipid levels.
      METHODS: The study subjects consisted of healthy individuals (male: 196, female:
      154; average age: 63.6 +/- 12.0 years) who were randomly selected from health
      screening. ApoE genotypes were identified by multi-AMRS PCR and both the ApoCI
      promoter polymorphisms and AvaII polymorphisms of the apoCII gene were detected
      by using PCR-RFLP. The serum lipid levels were determined using an automatic
      chemistry analyzer. RESULTS: For ApoE gene, the frequency of E3/3 was 73.4%, it
      represents the most common genotype from of the polymorphism. The frequencies of
      E2/2, E2/4 and E4/4 genotypes were all smaller than 1%. For the ApoCI locus, the
      frequencies of H1/ 1, H2/2 genotypes were 79.7% and 1.7%, respectively. Both the
      ApoE and ApoCI polymorphisms showed the lack of association with plasma levels in
      this population. The linkage disequilibrium between ApoE with ApoCI wasn't found,
      either. The allele frequencies of ApoCII gene were T1 : 70.7% and T2 : 29.3%,
      respectively. The TG level in subjects carrying with T1/2 (1.49 +/- 0.96 mmol/l)
      was significant higher than that in subjects with T1/1 (1.29 +/- 0.72 mmol/l), P
      < 0.05. No significant differences were found between male and female in genotype
      distribution and allele frequencies of the ApoE-CI-CII gene cluster. CONCLUSION:
      This result suggested that it might be one of the factors in explaining the lower
      prevalence rate of atherosclerosis in the China population.

PMID- 15862041
TI  - [Nutritional status survey in 200 of the Korean and Han nationality elderly in
      Yanji].
AB  - OBJECTIVE: To assess the nutritional status and dietary intake of the Korean and
      Han nationality elderly in Yanji. METHODS: We selected 200 of the Korean and Han
      nationality adults aged 60 and older and measured their blood pressure. Dietary
      survey was performed with 24-hour dietary recall method. RESULTS: (1) The daily
      average intake of energy surpassed recommended nutrient intake (RNI) value in
      male and amounted RNI in women. In the male, Breakfast energy intake ratio was
      significantly lower and supper energy intake ratio was significantly higher than
      female. Supper energy intake in male with hypertension was significantly higher
      than normal blood pressure. (2) The daily average intake of fat in the Korean was
      significantly lower than in Han nationality (P < 0.01), and also was lower than
      RNI value. The daily average intake of carbohydrate in the Korean was
      significantly higher than in Han nationality (P < 0.01). (3) The daily average
      intake of protein exceed RNI value in the Korean male and was slightly lower than
      RNI value in Han male and both nationality women. The daily average intake of
      protein in the Korean males was significantly higher than in Han males (P <
      0.01). The ratio of good protein was 35%-45% and bean protein exceed 15%. (4) The
      daily average intakes of calcium and vitamin A were only half RNI value and
      vitamin B2 lower than RNI values. CONCLUSION: The consumption of some nutrients
      among the Korean and Han nationality is inequality. The daily intake of calcium,
      vitamin A and vitamin B2 in elderly is seriously inadequate. Distribution of
      three meal energy is irrational and the high ratio of supper energy in male
      relates to hypertension.

PMID- 15862042
TI  - [Research on detection of Vibrio comma and Vibro parahaemolyticus from foodstuffs
      using MPCR methods].
AB  - OBJECTIVE: To establish a set of multi-PCR (MPCR) methods to detect Vibrio comma
      O1 serogroup (EVC) and O139 serogroup, and Vibrio parahaemolyticus rapidly and
      sensitively from foodstuffs. METHODS: Using T139 (specific gene of O139
      serogroup), ctxB and tcpA genes from V. comma, and tdh gene from V.
      parahaemolyticus as target sequences, we detected the anticipative amplified
      bands, whose sizes were relatively 417bp, 564bp, 471bp and 202bp. RESULTS:
      Excellent specificity of the amplified products could be found from both standard
      and wild strains of EVC, O139VC and V. parahaemolyticus. It also means that no
      amplified band was detected from total 35 strains of other bacilli, including
      salmonella, comma bacillus which do not belong to O1 and O139 serogroups. The
      detection limits of artificial contaminated samples such as tilapia flesh, oyster
      and mixture of tilapia intestines and gills were proved to be 22cfu/g in EVC,
      50cfu/g in O139 and 65cfu/g in V. parahaemolyticus. Besides, it took only 8-10
      hours to finish the whole process. CONCLUSION: Experiment results show that MPCR
      is a sensitive, convenient and time saving method suitable for detection.

PMID- 15862043
TI  - Quality patient care requires commitment, responsibility, and accountability.

PMID- 15862044
TI  - Product director clarifies point about Medicare coverage of oral anticancer
      drugs.

PMID- 15862045
TI  - The art and science of clinical teaching.

PMID- 15862047
TI  - Learning the practices of knowing and connecting: the voices of students.

PMID- 15862048
TI  - Inviting teaching behaviors of clinical faculty and nursing students' anxiety.
AB  - This study explored baccalaureate nursing students' perceptions of inviting
      teaching behaviors of clinical nursing faculty and students' state anxiety while
      interacting with faculty during clinical experiences. A total of 229 junior and
      senior generic baccalaureate nursing students comprised the sample. Participants
      completed three questionnaires: a demographic data questionnaire, the Clinical
      Teaching Survey, and a Self-Evaluation Questionnaire, designed to measure state
      anxiety. Results indicated there were moderate negative correlations between
      students' perceptions of the personally and professionally inviting teaching
      behaviors of clinical faculty and students' self-reports of state anxiety. A
      stepwise multiple regression analysis revealed that perceptions of personally
      inviting teaching behaviors explained 41% of the variance in students' state
      anxiety. Junior students rated faculty higher on personally and professionally
      inviting teaching behaviors than did senior students. However, both groups of
      students scored similarly on self-reports of state anxiety while interacting with
      clinical faculty. Findings indicate that clinical faculty should be intentionally
      aware of how their teaching behaviors are perceived by students and influence
      student anxiety during clinical experiences.

PMID- 15862049
TI  - Clinical grades: upward bound.
AB  - This study examined the relationship of grades earned in paired theory and
      clinical courses. Data collected during academic years 1997 to 2002 confirmed
      that grade inflation exists in clinical nursing courses. Problems involved in
      awarding grades for clinical performance are discussed (e.g., standards of
      clinical performance, methods used in evaluation of clinical performance, the
      impossibility of faculty omnipresence, the influence of student effort in
      grading, the effect of recency, the challenges of keeping good anecdotal
      records). Solutions to grading problems are proposed, including dividing up
      performance into agreed-on elements, measurement of these elements on a grading
      scale that allows for more differentiation of quality in evaluating clinical
      performance, assigning grades from the beginning of a clinical course,
      emphasizing all three domains of clinical practice, and evaluating student
      performance in both laboratory and, clinical settings.

PMID- 15862050
TI  - Companionship and education: a nursing student experience in palliative care.
AB  - Currently, major deficiencies exist in undergraduate nursing education for end-of
      life care. Nursing students report feeling anxious and unprepared to be with
      patients who are dying. A Palliative Care Companion program that allows
      undergraduate nursing students to volunteer to spend time with patients at the
      end of life provides a unique educational opportunity to enhance students'
      knowledge and attitudes toward palliative care. In addition, the program offers a
      service to patients and families by providing a nonmedical, caring human presence
      to patients who may be alone, lonely, or bored. In accordance with tenets of
      Experiential Learning Theory, a Palliative Care Companion program was developed
      and revised using feedback from initial participants and facilitators. Data
      collected during the first two semesters indicated increased knowledge of
      palliative care, improved attitudes about care at the end of life, and fewer
      concerns about providing nursing care to dying patients, when participating
      students were compared to their undergraduate peers.

PMID- 15862051
TI  - Application and evaluation of a caring code in clinical nursing education.
AB  - This study evaluated the effectiveness of the Caring Code, a tool for teaching
      caring to nursing students during clinical practice. An experimental,
      longitudinal design was used. A sample of 480 students from a 5-year junior
      nursing college program in Taiwan was randomly divided into experimental and
      control groups. Each member of the experimental group carried a copy of the
      Caring Code, the content of which was explained by the clinical instructors at
      the beginning of clinical practice, and about which reminders were provided
      weekly. A questionnaire was distributed to the patients during the nursing
      students' 1-year clinical practice, once prior to the implementation of the
      Caring Code and twice afterwards, to obtain quantitative data on the caring
      behaviors of the two student groups. Instructors and nursing students were
      interviewed for their experiences and perceptions of using the Caring Code. The
      Caring Code had a statistically significant positive effect on student caring
      behavior.

PMID- 15862052
TI  - A student home visiting program for vulnerable, community-dwelling older adults.
AB  - This article describes the experience of a baccalaureate community health nursing
      program during the implementation of a student home visiting program for
      vulnerable, community-dwelling older adults. The background, planning,
      implementation, and outcome of the program are described.

PMID- 15862053
TI  - Students' perceptions of effective and ineffective clinical instructors.
AB  - Clinical nursing faculty possess four categories of important qualities:
      professional competence, interpersonal relationship, personality characteristics,
      and teaching ability. The main purpose of this study was to understand of these
      four categories of qualities, which, taken together, was the main contributor to
      effectiveness differences among clinical nursing faculty. A total of 214 students
      from two nursing schools completed the questionnaire, using a 5-point Likert-type
      scale. The results showed that effective teachers possessed significantly high
      scores (> 4) in all of these four qualities. While the scores of ineffective
      teacher were lower (< 3) in all categories, except professional competence.
      Larger differences in scores between effective and ineffective teachers were
      found in the interpersonal relationship category, followed by the category of
      personality characteristics. Smaller differences in scores between effective and
      ineffective teachers were in the professional competence category, followed by
      the teaching ability category. From these results, we suggest that teachers'
      attitudes toward students, rather than their professional abilities, are the
      crucial difference between effective and ineffective teachers. This research also
      indicates that students from different nursing schools have similar opinions
      regarding this concern. Based on these findings, we highly recommend that
      teachers strive to improve their attitudes toward students as the best way to
      achieve the goals of clinical teaching.

PMID- 15862054
TI  - Does clinical experience make up for failure to keep up to date?

PMID- 15862055
TI  - Weighted event rates.

PMID- 15862056
TI  - Review: implantable cardioverter defibrillators reduce all-cause mortality in
      nonischemic cardiomyopathy.

PMID- 15862057
TI  - A prophylactically implanted cardioverter defibrillator did not reduce all-cause
      mortality after a recent myocardial infarction.

PMID- 15862058
TI  - Review: atenolol may be ineffective for reducing cardiovascular morbidity or all
      cause mortality in primary hypertension.

PMID- 15862059
TI  - Candesartan reduced cardiovascular mortality and morbidity in chronic heart
      failure with low ejection fraction.

PMID- 15862060
TI  - Picotamide reduced all-cause mortality more than aspirin in type 2 diabetes
      mellitus and peripheral arterial disease.

PMID- 15862061
TI  - Review: insulin monotherapy and insulin combined with oral hypoglycemic agents
      provide similar glycemic control.

PMID- 15862062
TI  - Review: short-acting insulin analogues reduce glycosylated hemoglobin more than
      regular human insulin but only in adults with type 1 diabetes.

PMID- 15862063
TI  - Diuretic-based therapy reduced cardiovascular mortality in older patients with
      isolated systolic hypertension and diabetes.

PMID- 15862064
TI  - Trandolapril delayed persistent microalbuminuria in hypertension, type 2
      diabetes, and normoalbuminuria.

PMID- 15862065
TI  - Trandolapril did not reduce cardiovascular death or other events in stable
      coronary artery disease.

PMID- 15862066
TI  - Review: bupropion and nortriptyline each increase smoking cessation rates.

PMID- 15862067
TI  - Intradermal injection of reduced-dose influenza vaccine was highly immunogenic in
      persons </= 60 years of age but less so in persons > 60 years.

PMID- 15862068
TI  - Intradermal injection of reduced-dose influenza vaccine was immunogenic in young
      adults.

PMID- 15862069
TI  - Review: vaccination reduces the incidence of serologically confirmed influenza in
      healthy adults.

PMID- 15862070
TI  - Review: low-molecular-weight heparin reduces recurrent venous thromboembolism
      better than unfractionated heparin.

PMID- 15862071
TI  - Review: n-3 fatty acids do not reduce mortality, cardiovascular events, or cancer
      in patients at risk for cardiovascular disease.

PMID- 15862072
TI  - High-intensity exercise for rheumatoid arthritis was associated with less joint
      damage of the hands and feet than physical therapy.

PMID- 15862073
TI  - Review: proton-pump inhibitor therapy reduces symptoms in nonulcer dyspepsia
      better than placebo.

PMID- 15862074
TI  - Review: misoprostol or COX-2-specific or selective NSAIDs reduce gastrointestinal
      complications and symptomatic ulcers.

PMID- 15862075
TI  - Celecoxib was noninferior to diclofenac plus omeprazole for preventing
      gastroduodenal ulcer recurrence in high-risk patients with arthritis.

PMID- 15862076
TI  - Review: intravenous metoclopramide is better than placebo for reducing pain in
      acute migraine in the emergency department.

PMID- 15862077
TI  - Review: some therapies for treating the irritable bowel syndrome may be effective
      for symptom improvement.

PMID- 15862078
TI  - Citalopram did not differ from placebo for treatment of depression in patients
      >/= 75 years of age.

PMID- 15862079
TI  - Computed tomographic angiography and magnetic resonance angiography were
      specific, but could not rule out renal artery stenosis.

PMID- 15862080
TI  - A hemoglobin level 140 g/L was associated with a lower mortality risk than levels
      </= 120 g/L in older women with disabilities.

PMID- 15862081
TI  - Digoxin-specific antibody fragments: how much and when?
AB  - Digitalis glycoside poisoning is an important clinical problem and the
      development of digoxin-specific antibody fragments (Fab) 30 years ago has changed
      clinical practice. Nevertheless, doubts still exist as to the appropriate dose
      indications for therapy. This paper reviews relevant literature, describes the
      difficulties associated with current treatment protocols and proposes an approach
      to therapy, which is based on theoretical principles and evidence gleaned from
      currently available clinical data sets. In patients with 'acute' poisoning, serum
      digoxin concentrations do not equate to the total body burden, as tissue
      distribution will not have occurred, and the calculations for present protocols,
      which use serum concentrations, are therefore likely to result in too much
      antibody being administered. Since a therapeutic quantity of digoxin will have
      little effect in a normal individual, complete neutralisation of all digoxin is
      also unnecessary. The pharmacokinetic and dynamic logic of using a smaller
      initial loading dose than predicted from total body calculations is rational. It
      is recommended that half the calculated loading dose, either based on serum
      concentration or history, should be administered and the impact on clinical
      features observed. If a clinical response is not seen within 1-2 hours, a further
      similar dose should be given. In the event of a full response, patients should be
      monitored for 6-12 hours; a second dose should only be given in the event of
      recurrence of toxicity. In patients with 'chronic' digoxin poisoning, the serum
      digoxin concentration will reflect the total body load. However, since such
      patients are invariably receiving digoxin for therapeutic purposes, full
      neutralisation is again not indicated. In addition, tissue redistribution of
      digoxin from deeper stores will occur following the binding of biologically
      active digoxin in the circulation. This process will occur over a number of hours
      and if the total calculated dose of antibody is administered in a single bolus,
      significant quantities will be excreted prior to redistribution of digoxin.
      Pharmacokinetic logic, therefore, suggests that half the calculated loading dose,
      based on serum concentration, should be administered and the impact on clinical
      features observed; a second dose should be given in the event of recurrence of
      toxicity.

PMID- 15862082
TI  - The role of diazepam in the treatment of nerve agent poisoning in a civilian
      population.
AB  - The main site of action of diazepam, as with other benzodiazepines, is at the
      GABA(A) receptor, although it has been suggested that some of the potentially
      beneficial actions of diazepam in nerve agent poisoning are mediated through
      other means. It is likely that convulsions may have long-term sequelae in the
      central nervous system, because of damage by anoxia and/or excitotoxicity.
      Numerous pharmacodynamic studies of the action of diazepam in animals
      experimentally poisoned with nerve agents have been undertaken. In nearly all of
      these, diazepam has been studied in combination with other antidotes, such as
      atropine and/or pyridinium oximes, sometimes in combination with pyridostigmine
      pretreatment. These studies show that diazepam is an efficacious anticonvulsant
      in nerve agent poisoning. There is considerable experimental evidence to support
      the hypothesis that diazepam (and other anticonvulsants) may prevent structural
      damage to the central nervous system as evidenced by neuropathological changes
      such as neuronal necrosis at autopsy. In instances of nerve agent poisoning
      during terrorist use in Japan, diazepam seems to have been an effective
      anticonvulsant. Consequently, the use of diazepam is an important part of the
      treatment regimen of nerve agent poisoning, the aim being to prevent convulsions
      or reduce their duration. Diazepam should be given to patients poisoned with
      nerve agents whenever convulsions or muscle fasciculation are present. In severe
      poisoning, diazepam administration should be considered even before these
      complications occur. Diazepam is also useful as an anxiolytic in those exposed to
      nerve agents.

PMID- 15862083
TI  - Glyphosate poisoning.
AB  - Glyphosate is used extensively as a non-selective herbicide by both professional
      applicators and consumers and its use is likely to increase further as it is one
      of the first herbicides against which crops have been genetically modified to
      increase their tolerance. Commercial glyphosate-based formulations most commonly
      range from concentrates containing 41% or more glyphosate to 1% glyphosate
      formulations marketed for domestic use. They generally consist of an aqueous
      mixture of the isopropylamine (IPA) salt of glyphosate, a surfactant, and various
      minor components including anti-foaming and colour agents, biocides and inorganic
      ions to produce pH adjustment. The mechanisms of toxicity of glyphosate
      formulations are complicated. Not only is glyphosate used as five different salts
      but commercial formulations of it contain surfactants, which vary in nature and
      concentration. As a result, human poisoning with this herbicide is not with the
      active ingredient alone but with complex and variable mixtures. Therefore, It is
      difficult to separate the toxicity of glyphosate from that of the formulation as
      a whole or to determine the contribution of surfactants to overall toxicity.
      Experimental studies suggest that the toxicity of the surfactant,
      polyoxyethyleneamine (POEA), is greater than the toxicity of glyphosate alone and
      commercial formulations alone. There is insufficient evidence to conclude that
      glyphosate preparations containing POEA are more toxic than those containing
      alternative surfactants. Although surfactants probably contribute to the acute
      toxicity of glyphosate formulations, the weight of evidence is against
      surfactants potentiating the toxicity of glyphosate. Accidental ingestion of
      glyphosate formulations is generally associated with only mild, transient,
      gastrointestinal features. Most reported cases have followed the deliberate
      ingestion of the concentrated formulation of Roundup (The use of trade names is
      for product identification purposes only and does not imply endorsement.) (41%
      glyphosate as the IPA salt and 15% POEA). There is a reasonable correlation
      between the amount ingested and the likelihood of serious systemic sequelae or
      death. Advancing age is also associated with a less favourable prognosis.
      Ingestion of >85 mL of the concentrated formulation is likely to cause
      significant toxicity in adults. Gastrointestinal corrosive effects, with mouth,
      throat and epigastric pain and dysphagia are common. Renal and hepatic impairment
      are also frequent and usually reflect reduced organ perfusion. Respiratory
      distress, impaired consciousness, pulmonary oedema, infiltration on chest x-ray,
      shock, arrythmias, renal failure requiring haemodialysis, metabolic acidosis and
      hyperkalaemia may supervene in severe cases. Bradycardia and ventricular
      arrhythmias are often present pre-terminally. Dermal exposure to ready-to-use
      glyphosate formulations can cause irritation and photo-contact dermatitis has
      been reported occasionally; these effects are probably due to the preservative
      Proxel (benzisothiazolin-3-one). Severe skin burns are very rare. Inhalation is a
      minor route of exposure but spray mist may cause oral or nasal discomfort, an
      unpleasant taste in the mouth, tingling and throat irritation. Eye exposure may
      lead to mild conjunctivitis, and superficial corneal injury is possible if
      irrigation is delayed or inadequate. Management is symptomatic and supportive,
      and skin decontamination with soap and water after removal of contaminated
      clothing should be undertaken in cases of dermal exposure.

PMID- 15862084
TI  - Oxidant stress and haemolysis of the human erythrocyte.
AB  - The erythrocyte is a highly specialised cell with a limited metabolic repertoire.
      As an oxygen shuttle, it must continue to perform this essential task while
      exposed to a wide range of environments on each vascular circuit, and to a
      variety of xenobiotics across its lifetime. During this time, it must
      continuously ward off oxidant stress on the haeme iron, the globin chain and on
      other essential cellular molecules. Haemolysis, the acceleration of the normal
      turnover of senescent erythrocytes, follows severe and irreversible oxidant
      injury. A detailed understanding of the molecular mechanisms underlying oxidant
      injury and its reversal, and of the clinical and laboratory features of
      haemolysis is important to the medical toxicologist. This review will also
      briefly review glucose-6-phosphate deficiency, a common but heterogeneous range
      of enzyme-deficient states, which impairs the ability of the erythrocyte to
      respond to oxidant injury.

PMID- 15862085
TI  - The use of the osmole gap as a screening test for the presence of exogenous
      substances.
AB  - The rapid and accurate diagnosis of toxic alcohol poisoning due to methanol
      (methyl alcohol) [MeOH] and ethylene glycol (EG), is paramount in preventing
      serious adverse outcomes. The quantitative measurement of specific serum levels
      of these substances using gas chromatography is expensive, time consuming and
      generally only available at major tertiary-care facilities. Therefore, because
      these toxic substances are osmotically active and the measurement of serum
      osmolality is easily performed and more readily available, the presence of an
      osmole gap (OG) has been adopted as an alternative screening test. By definition,
      the OG is the difference between the measured serum osmolality determined using
      the freezing point depression (Osm(m)) and the calculated serum molarity (Mc),
      which is estimated from the known and readily measurable osmotically active
      substances in the serum, in particular sodium, urea, glucose, and potassium and
      ethanol (alcohol). Thus, the OG=Osm(m)-Mc, and an OG above a specific threshold
      (the threshold of positivity) suggests the presence of unmeasured osmotically
      active substances, which could be indicative of a toxic exposure. The objectives
      of this study were to review the principles of evaluating screening tests, the
      theory behind the OG as a screening test and the literature upon which the
      adoption of the OG as a screening test has been based. This review revealed that
      there have been numerous equations derived and proposed for the estimation of the
      Mc, with the objective of developing empirical evidence of the best equation for
      the determination of the OG and ultimately the utility of OG as a screening test.
      However, the methods and statistical analysis employed have generally been
      inconsistent with recommended guidelines for screening test evaluation and
      although many equations have been derived, they have not been appropriately
      validated. Specific evidence of the clinical utility of the OG requires that a
      threshold of positivity be definitively established, and the sensitivity and
      specificity of the OG in patients exposed to either EG or MeOH be measured.
      However, the majority of studies to date have only evaluated the relationship
      between the Osm(m) (mmol/kg H2O) and the Mc (mmol/L) in patients that have not
      been exposed to either MeOH or EG. While some studies have evaluated the
      relationship between the OG and serum ethanol concentration, these findings
      cannot be extrapolated to the use of the OG to screen for toxic alcohol exposure.
      This review shows that there has not been an appropriately designed empirical
      evaluation of the diagnostic utility of the OG and that its clinical utility
      remains hypothetical, having been theoretically extrapolated from the non
      poisoned population.

PMID- 15862086
TI  - The irrationality of the present use of the osmole gap: applicable physical
      chemistry principles and recommendations to improve the validity of current
      practices.
AB  - The present clinical use of serum osmometry is erroneous in two respects. The
      first, and the most important, is the incorrect assumption that serum behaves as
      a dilute 'ideal' solution and that the osmotic activity of a substance depends
      solely on the number of solute particles. The amount of variance from ideal
      behaviour of serum containing an exogenous substance is expressed by the osmotic
      coefficient (phi). We have calculated the osmotic coefficient for serum
      containing ethanol (alcohol) and recommend that the osmotic coefficient for serum
      containing other low molecular weight substances such as methanol (methyl
      alcohol), isopropyl alcohol and ethylene glycol also be calculated. This is
      necessary for the accurate calculation of the contribution of these substances to
      the serum osmolality.Secondly, the practice of subtracting the calculated serum
      molarity from measured serum osmolality is not valid since it represents a
      mathematically improper expression. The units of these two terms are different.
      The 'osmole gap' (OG) is typically viewed as the difference between serum
      osmolality determined by an osmometer and the estimated total molarity of solute
      in serum by directly measuring the concentration of several substances and then
      substituting them into a published formula. Some authors call this sum the
      calculated or estimated osmolarity but, because the concentrations are measured
      directly and not with an osmometer, the calculated term represents molarity. The
      units of osmolality are mmol/kg of H2O and the units of molarity are mmol/L.
      Therefore, the practice of subtracting calculated serum molarity from measured
      serum osmolality is not mathematically sound and is an oversimplification for
      ease of application. This mathematical transgression necessarily adds an error to
      the incorrectly calculated OG. Despite this, the OG is commonly used in clinical
      medicine. Serum osmolality can be converted to molarity provided the weight
      percentage and the density of the solution are known and thus, we recommend that
      this conversion be done prior to calculation of the gap. We recommend that the
      gap between measured serum osmolarity and calculated serum molarity be called the
      'osmolar gap'. After having corrected for non-ideality for serum and for
      inconsistency of units, the standard value and reference range for this gap must
      be determined in an adequate number of patient populations and in a variety of
      clinical settings. An example of this determination, using data from a group of
      ethanol-poisoned patients is given. This correction should be applied before the
      evaluation of the osmolar gap as a screening test for other low molecular weight
      substances proceeds.

PMID- 15862087
TI  - Fifty good years.

PMID- 15862088
TI  - Phytoremediation.
AB  - Phytoremediation, the use of plants and their associated microbes for
      environmental cleanup, has gained acceptance in the past 10 years as a cost
      effective, noninvasive alternative or complementary technology for engineering
      based remediation methods. Plants can be used for pollutant stabilization,
      extraction, degradation, or volatilization. These different phytoremediation
      technologies are reviewed here, including their applicability for various organic
      and inorganic pollutants, and most suitable plant species. To further enhance the
      efficiency of phytoremediation, there is a need for better knowledge of the
      processes that affect pollutant availability, rhizosphere processes, pollutant
      uptake, translocation, chelation, degradation, and volatilization. For each of
      these processes I review what is known so far for inorganic and organic
      pollutants, the remaining gaps in our knowledge, and the practical implications
      for designing phytoremediation strategies. Transgenic approaches to enhance these
      processes are also reviewed and discussed.

PMID- 15862089
TI  - Calcium oxalate in plants: formation and function.
AB  - Calcium oxalate (CaOx) crystals are distributed among all taxonomic levels of
      photosynthetic organisms from small algae to angiosperms and giant gymnosperms.
      Accumulation of crystals by these organisms can be substantial. Major functions
      of CaOx crystal formation in plants include high-capacity calcium (Ca) regulation
      and protection against herbivory. Ultrastructural and developmental analyses have
      demonstrated that this biomineralization process is not a simple random physical
      chemical precipitation of endogenously synthesized oxalic acid and
      environmentally derived Ca. Instead, crystals are formed in specific shapes and
      sizes. Genetic regulation of CaOx formation is indicated by constancy of crystal
      morphology within species, cell specialization, and the remarkable coordination
      of crystal growth and cell expansion. Using a variety of approaches, researchers
      have begun to unravel the exquisite control mechanisms exerted by cells
      specialized for CaOx formation that include the machinery for uptake and
      accumulation of Ca, oxalic acid biosynthetic pathways, and regulation of crystal
      growth.

PMID- 15862090
TI  - Starch degradation.
AB  - Recent research reveals that starch degradation in Arabidopsis leaves at night is
      significantly different from the "textbook" version of this process. Although
      parts of the pathway are now understood, other parts remain to be discovered.
      Glucans derived from starch granules are hydrolyzed via beta-amylase to maltose,
      which is exported from the chloroplast. In the cytosol maltose is the substrate
      for a transglucosylation reaction, producing glucose and a glucosylated acceptor
      molecule. The enzyme that attacks the starch granule to release glucans is not
      known, nor is the nature of the cytosolic acceptor molecule. An Arabidopsis-type
      pathway may operate in leaves of other species, and in nonphotosynthetic organs
      that accumulate starch transiently. However, in starch-storing organs such as
      cereal endosperms and legume seeds, the process differs from that in Arabidopsis
      and may more closely resemble the textbook pathway. We discuss the differences in
      relation to the biology of each system.

PMID- 15862091
TI  - CO2 concentrating mechanisms in algae: mechanisms, environmental modulation, and
      evolution.
AB  - The evolution of organisms capable of oxygenic photosynthesis paralleled a long
      term reduction in atmospheric CO2 and the increase in O2. Consequently, the
      competition between O2 and CO2 for the active sites of RUBISCO became more and
      more restrictive to the rate of photosynthesis. In coping with this situation,
      many algae and some higher plants acquired mechanisms that use energy to increase
      the CO2 concentrations (CO2 concentrating mechanisms, CCMs) in the proximity of
      RUBISCO. A number of CCM variants are now found among the different groups of
      algae. Modulating the CCMs may be crucial in the energetic and nutritional
      budgets of a cell, and a multitude of environmental factors can exert regulatory
      effects on the expression of the CCM components. We discuss the diversity of
      CCMs, their evolutionary origins, and the role of the environment in CCM
      modulation.

PMID- 15862092
TI  - Solute transporters of the plastid envelope membrane.
AB  - Plastids are metabolically extraordinarily active and versatile organelles that
      are found in all plant cells with the exception of angiosperm pollen grains. Many
      of the plastid-localized biochemical pathways depend on precursors from the
      cytosol and, in turn, many cytosolic pathways depend on the supply of precursor
      molecules from the plastid stroma. Hence, a massive traffic of metabolites occurs
      across the permeability barrier between plastids and cytosol that is called the
      plastid envelope membrane. Many of the known plastid envelope solute transporters
      have been identified by biochemical purification and peptide sequencing. This
      approach is of limited use for less abundant proteins and for proteins of plastid
      subtypes that are difficult to isolate in preparative amounts. Hence, the
      majority of plastid envelope membrane transporters are not yet identified at the
      molecular level. The availability of fully sequenced plant genomes, the progress
      in bioinformatics to predict membrane transporters localized in plastids, and the
      development of highly sensitive proteomics techniques open new avenues toward
      identifying additional, to date unknown, plastid envelope membrane transporters.

PMID- 15862093
TI  - Abscisic acid biosynthesis and catabolism.
AB  - The level of abscisic acid (ABA) in any particular tissue in a plant is
      determined by the rate of biosynthesis and catabolism of the hormone. Therefore,
      identifying all the genes involved in the metabolism is essential for a complete
      understanding of how this hormone directs plant growth and development. To date,
      almost all the biosynthetic genes have been identified through the isolation of
      auxotrophic mutants. On the other hand, among several ABA catabolic pathways,
      current genomic approaches revealed that Arabidopsis CYP707A genes encode ABA 8'
      hydroxylases, which catalyze the first committed step in the predominant ABA
      catabolic pathway. Identification of ABA metabolic genes has revealed that
      multiple metabolic steps are differentially regulated to fine-tune the ABA level
      at both transcriptional and post-transcriptional levels. Furthermore, recent
      ongoing studies have given new insights into the regulation and site of ABA
      metabolism in relation to its physiological roles.

PMID- 15862094
TI  - Redox regulation: a broadening horizon.
AB  - Initially discovered in the context of photosynthesis, regulation by change in
      the redox state of thiol groups (S-S <--> 2SH) is now known to occur throughout
      biology. Several systems, each linking a hydrogen donor to an intermediary
      disulfide protein, act to effect changes that alter the activity of target
      proteins: the ferredoxin/thioredoxin system, comprised of reduced ferredoxin, a
      thioredoxin, and the enzyme, ferredoxin-thioredoxin reductase; the
      NADP/thioredoxin system, including NADPH, a thioredoxin, and NADP-thioredoxin
      reductase; and the glutathione/glutaredoxin system, composed of reduced
      glutathione and a glutaredoxin. A related disulfide protein, protein disulfide
      isomerase (PDI) acts in protein assembly. Regulation linked to plastoquinone and
      signaling induced by reactive oxygen species (ROS) and other agents are also
      being actively investigated. Progress made on these systems has linked redox to
      the regulation of an increasing number of processes not only in plants, but in
      other types of organisms as well. Research in areas currently under exploration
      promises to provide a fuller understanding of the role redox plays in cellular
      processes, and to further the application of this knowledge to technology and
      medicine.

PMID- 15862095
TI  - Endocytotic cycling of PM proteins.
AB  - Plasma membrane protein internalization and recycling mechanisms in plants share
      many features with other eukaryotic organisms. However, functional and structural
      differences at the cellular and organismal level mandate specialized mechanisms
      for uptake, sorting, trafficking, and recycling in plants. Recent evidence of
      plasma membrane cycling of members of the PIN auxin efflux facilitator family and
      the KAT1 inwardly rectifying potassium channel demonstrates that endocytotic
      cycling of some form occurs in plants. However, the mechanisms underlying protein
      internalization and the signals that stimulate endocytosis of proteins from the
      cell-environment interface are poorly understood. Here we summarize what is known
      of endocytotic cycling in animals and compare those mechanisms with what is known
      in plants. We discuss plant orthologs of mammalian-trafficking proteins involved
      in endocytotic cycling. The use of the styryl dye FM4-64 to define the course of
      endocytotic uptake and the fungal toxin brefeldin A to dissect the
      internalization pathways are particularly emphasized. Additionally, we discuss
      progress in identifying distinct endosomal populations marked by the small
      GTPases Ara6 and Ara7 as well as recently described examples of apparent cycling
      of plasma membrane proteins.

PMID- 15862096
TI  - Molecular physiology of legume seed development.
AB  - Legume seed development is characterized by progressive differentiation of organs
      and tissues resulting in developmental gradients. The whole process is prone to
      metabolic control, and distinct metabolite profiles specify the differentiation
      state. Whereas early embryo growth is mainly maternally controlled, the
      transition into maturation implies a switch to filial control. A signaling
      network involving sugars, ABA, and SnRK1 kinases governs maturation. Processes of
      maturation are activated by changing oxygen/energy levels and/or a changing
      nutrient state, which trigger responses at the level of transcription and protein
      phosphorylation. This way seed metabolism becomes adapted to altering conditions.
      In maturing cotyledons photoheterotrophic metabolism improves internal oxygen
      supply and biosynthetic fluxes and influences assimilate partitioning. Transgenic
      legumes with changed metabolic pathways and seed composition provide suitable
      models to study pathway regulation and metabolic control. At the same time,
      desirable improvements of seed quality and yield may be achieved.

PMID- 15862097
TI  - Cytokinesis in higher plants.
AB  - Cytokinesis partitions the cytoplasm between two or more nuclei. In higher
      plants, cytokinesis is initiated by cytoskeleton-assisted targeted delivery of
      membrane vesicles to the plane of cell division, followed by local membrane
      fusion to generate tubulo-vesicular networks. This initial phase of cytokinesis
      is essentially the same in diverse modes of plant cytokinesis whereas the
      subsequent transformation of the tubulo-vesicular networks into the partitioning
      membrane may be different between systems. This review focuses on membrane and
      cytoskeleton dynamics in cell plate formation and expansion during somatic
      cytokinesis.

PMID- 15862098
TI  - Evolution of flavors and scents.
AB  - The world is filled with flavors and scents, which are the result of volatile
      compounds produced and emitted by plants. These specialized metabolites are the
      products of specific metabolic pathways. The terpenoid, fatty acid, and
      phenylpropanoid pathways contribute greatly to production of volatile compounds.
      Mechanisms that lead to evolution of volatile production in plants include gene
      duplication and divergence, convergent evolution, repeated evolution, and
      alteration of gene expression, caused by a number of factors, followed by change
      in enzyme specificity. Many examples of these processes are now available for
      three important gene families involved in production of volatile metabolites: the
      small molecule O-methyltransferases, the acyltransferases, and the terpene
      synthases. Examples of these processes in these gene families are found in roses,
      Clarkia breweri, and sweet basil, among others. Finally, evolution of volatile
      emission will be an exciting field of study for the foreseeable future.

PMID- 15862099
TI  - Biology of chromatin dynamics.
AB  - During the development of a multicellular organism, cell differentiation involves
      activation and repression of transcription programs that must be stably
      maintained during subsequent cell divisions. Chromatin remodeling plays a crucial
      role in regulating chromatin states that conserve transcription programs and
      provide a mechanism for chromatin states to be maintained as cells proliferate, a
      process referred to as epigenetic inheritance. A large number of factors and
      protein complexes are now known to be involved in regulating the dynamic states
      of chromatin structure. Their biological functions and molecular mechanisms are
      beginning to be revealed.

PMID- 15862100
TI  - Shoot branching.
AB  - All plant shoots can be described as a series of developmental modules termed
      phytomers, which are produced from shoot apical meristems. A phytomer generally
      consists of a leaf, a stem segment, and a secondary shoot meristem. The fate and
      activity adopted by these secondary, axillary shoot meristems is the major source
      of evolutionary and environmental diversity in shoot system architecture.
      Axillary meristem fate and activity are regulated by the interplay of genetic
      programs with the environment. Recent results show that these inputs are
      channeled through interacting hormonal and transcription factor regulatory
      networks. Comparison of the factors involved in regulating the function of
      diverse axillary meristem types both within and between species is gradually
      revealing a pattern in which a common basic program has been modified to produce
      a range of axillary meristem types.

PMID- 15862101
TI  - Protein splicing elements and plants: from transgene containment to protein
      purification.
AB  - Protein splicing elements, termed inteins, have been discovered in all the
      domains of life. Basic research on inteins has led to a greater understanding of
      how they mediate the protein splicing process. Because inteins are natural
      protein engineering elements they have been harnessed for use in a number of
      applications, including protein purification, protein semisynthesis, and in vivo
      and in vitro protein modifications. This review focuses on the use of inteins in
      plants. A split-gene technique utilizes inteins to reconstitute the activity of a
      transgene product with the goal of limiting the spread of transgenes from a
      genetically modified plant to a weedy relative. Furthermore, merging the intein
      tag for protein purification with the large protein yields possible with plants
      has the potential to produce pharmaceutically important proteins. Finally,
      relevant techniques that may be used in plants in the future are discussed.

PMID- 15862102
TI  - Molecular genetic analyses of microsporogenesis and microgametogenesis in
      flowering plants.
AB  - In flowering plants, male reproductive development requires the formation of the
      stamen, including the differentiation of anther tissues. Within the anther, male
      meiosis produces microspores, which further develop into pollen grains, relying
      on both sporophytic and gametophytic gene functions. The mature pollen is
      released when the anther dehisces, allowing pollination to occur. Molecular
      studies have identified a large number of genes that are expressed during stamen
      and pollen development. Genetic analyses have demonstrated the function of some
      of these genes in specifying stamen identity, regulating anther cell division and
      differentiation, controlling male meiosis, supporting pollen development, and
      promoting anther dehiscence. These genes encode a variety of proteins, including
      transcriptional regulators, signal transduction proteins, regulators of protein
      degradation, and enzymes for the biosynthesis of hormones. Although much has been
      learned in recent decades, much more awaits to be discovered and understood; the
      future of the study of plant male reproduction remains bright and exciting with
      the ever-growing tool kits and rapidly expanding information and resources for
      gene function studies.

PMID- 15862103
TI  - Plant-specific calmodulin-binding proteins.
AB  - Calmodulin CaM is the most prominent Ca2+ transducer in eukaryotic cells,
      regulating the activity of numerous proteins with diverse cellular functions.
      Many features of CaM and its downstream targets are similar in plants and other
      eukaryotes. However, plants possess a unique set of CaM-related proteins, and
      several unique CaM target proteins. This review discusses recent progress in
      identifying plant-specific CaM-binding proteins and their roles in response to
      biotic and abiotic stresses and development. The review also addresses aspects
      emerging from recent structural studies of CaM interactions with target proteins
      relevant to plants.

PMID- 15862104
TI  - Self-incompatibility in plants.
AB  - Sexual reproduction in many flowering plants involves self-incompatibility (SI),
      which is one of the most important systems to prevent inbreeding. In many
      species, the self-/nonself-recognition of SI is controlled by a single
      polymorphic locus, the S-locus. Molecular dissection of the S-locus revealed that
      SI represents not one system, but a collection of divergent mechanisms. Here, we
      discuss recent advances in the understanding of three distinct SI mechanisms,
      each controlled by two separate determinant genes at the S-locus. In the
      Brassicaceae, the determinant genes encode a pollen ligand and its stigmatic
      receptor kinase; their interaction induces incompatible signaling(s) within the
      stigma papilla cells. In the Solanaceae-type SI, the determinants are a
      ribonuclease and an F-box protein, suggesting the involvement of RNA and protein
      degradation in the system. In the Papaveraceae, the only identified female
      determinant induces a Ca2+-dependent signaling network that ultimately results in
      the death of incompatible pollen.

PMID- 15862105
TI  - Remembering winter: toward a molecular understanding of vernalization.
AB  - Exposure to the prolonged cold of winter is an important environmental cue that
      favors flowering in the spring in many types of plants. The process by which
      exposure to cold promotes flowering is known as vernalization. In Arabidopsis and
      certain cereals, the block to flowering in plants that have not been vernalized
      is due to the expression of flowering repressors. The promotion of flowering is
      due to the cold-mediated suppression of these repressors. Recent work has
      demonstrated that covalent modifications of histones in the chromatin of target
      loci are part of the molecular mechanism by which certain repressors are silenced
      during vernalization.

PMID- 15862106
TI  - New insights to the function of phytopathogenic bacterial type III effectors in
      plants.
AB  - Phytopathogenic bacteria use the type III secretion system (TTSS) to inject
      effector proteins into plant cells. This system is essential for bacteria to
      multiply in plant tissue and to promote the development of disease symptoms.
      Until recently, little was known about the function of TTSS effectors in
      bacterial-plant interactions. New studies dissecting the molecular and
      biochemical action of TTSS effectors show that these proteins contribute to
      bacterial pathogenicity by interfering with plant defense signal transduction.
      These investigations provide us with a fresh view of how bacteria manipulate
      plant physiology to colonize their hosts.

PMID- 15862107
TI  - Molecular and cellular mechanisms for the polarized sorting of serotonin
      receptors: relevance for genesis and treatment of psychosis.
AB  - The 5-HT2A serotonin receptor represents the principal molecular target for the
      actions of both classic hallucinogens, which function as agonists, and atypical
      antipsychotic drugs, which function as inverse agonists. Pharmacological agents
      that modify the activity of 5-HT2A receptors are known to modulate human
      perception and cognition. 5-HT2A receptors are found predominantly in the apical
      dendritic segment and dendritic spines of cortical pyramidal neurons. This review
      discusses our current understanding of the molecular and cellular mechanisms
      governing the preferential targeting of 5-HT2A receptors to apical dendrites and
      dendritic spines. Uncovering the processes responsible for the polarization of 5
      HT2A receptors to neuronal subdomains will likely provide crucial insights into
      the modulating mechanisms that can affect human cognition and perception.

PMID- 15862108
TI  - Adenosine and adenine nucleotides as regulators of cerebral blood flow: roles of
      acidosis, cell swelling, and KATP channels.
AB  - A considerable volume of evidence implicates the purine adenosine in the
      regulation of cerebral blood flow during states such as hypotension, neural
      activation, hypoxia/ischemia, and hypercapnia/acidosis. The aim of this review is
      to describe developments in our understanding of the roles that adenosine and the
      adenine nucleotides play in cerebral blood flow control, with some comparisons to
      coronary blood flow. The first part of the review focuses on the categorization
      of receptors for adenosine (A1, A2A, A2B, and A3) and the adenine nucleotides,
      ATP and ADP (P2X and P2Y). Frequently used agonists and antagonists for these
      different receptors are mentioned. A description follows of the distribution of
      these different receptors in cerebral arterioles. The second part of the review
      initially deals with the literature on the release of adenosine and adenine
      nucleotides into the extracellular space of the brain, describing the various
      techniques used to make these measurements and assessing the pitfalls associated
      with their use. This is followed by a discussion of the factors affecting purine
      release, which include cell swelling and acidosis. The third section evaluates
      the role of smooth muscle potassium channels in controlling arteriolar diameter.
      There is evidence for an important role of KATP and KCa channels, but less is
      known about the contributions of voltage-dependent (KV) and inwardly rectifying
      (KIR) channels. This section ends with a discussion on the reported inhibitory
      effect of nitric oxide synthase inhibitors on the KATP channel and the
      consequences of such an action for the interpretation of much of the published
      work on nitric oxide as a regulator of cerebral blood flow. The fourth section
      evaluates the data supporting a role of adenosine and ATP in the regulation of
      cerebral blood flow during autoregulation, hypotension, neural activity, hypoxia/
      ischemia, and hypercapnia. Studies using antagonists and potentiators of
      adenosine's actions have led to the conclusion that adenosine is involved in
      vascular flow control, matching metabolic activity to blood flow in all of these
      conditions, possibly with the exceptions of autoregulation at mean arterial blood
      pressures above approximately 60 mmHg. Evidence is presented for a major role of
      A2A, and a more limited role of A2B receptors, in balancing blood flow with
      metabolism. The primary effect of receptor occupancy is activation of KATP and
      KCa channels with smooth muscle relaxation and elevated blood flow rates. There
      are presently fewer data on ATP's participation in flow control, but recent
      evidence regarding glial cell control of cerebral arteriolar diameter suggests
      that this may be an important mechanism. The semi-final section, which briefly
      describes the evidence for a comparable role of adenosine in regulating coronary
      blood flow, is followed by a concluding statement reaffirming the importance of
      adenosine as a cerebral blood flow regulator.

PMID- 15862109
TI  - Morphinan neuroprotection: new insight into the therapy of neurodegeneration.
AB  - Neuro-inflammation plays a pivotal role in numerous neurodegenerative disorders,
      such as Parkinson's disease (PD). Traditional anti-inflammatory drugs have
      limited therapeutic use because of their narrow spectrum and severe side effects
      after long-term use. Morphinans are a class of compounds containing the basic
      morphine structure. The following review will describe novel neuroprotective
      effects of several morphinans in multiple inflammatory disease models. The
      potential therapeutic utility and underlying mechanisms of morphinan
      neuroprotection are discussed.

PMID- 15862110
TI  - Hydrogels for pharmaceutical and biomedical applications.
AB  - Hydrogels are crosslinked hydrophilic polymer structures that can imbibe large
      amounts of water or biological fluids. Hydrogels are one of the upcoming classes
      of polymer-based systems that embrace numerous biomedical and pharmaceutical
      applications. This review discusses various parameters of hydrogels such as
      surface properties, water content and swelling behavior, effect of nature of
      polymer, ionic content, and thermodynamics, all of which can influence the
      biomedical usage of hydrogels. Meanwhile, intelligent or environment-sensitive
      hydrogels and bioadhesive hydrogels continue to be important materials for
      medical applications; therefore, a part of this review is devoted to some of
      their important classes. Hydrogels are extensively used for various biomedical
      applications--tissue engineering, molecular imprinting, wound dressings
      materials, immunoisolation, drug delivery, etc. Thus, this review aims to throw
      light on the numerous applications that hydrogels have in the biomedical arena.

PMID- 15862111
TI  - Particulate delivery systems for vaccines.
AB  - This review focuses on the use of particulate delivery systems for the purposes
      of immunization. This includes poly(lactide-co-glycolide) (PLGA), ISCOMs,
      liposomes, niosomes, virosomes, chitosan, and other biodegradable polymers. These
      systems are evaluated in terms of their use as carriers for protein subunit and
      DNA vaccines. There is an extensive focus on recent literature, the understanding
      of biological interactions, and relation of this to our present understanding of
      immunological mechanisms of action. In addition, there is consideration of
      formulation techniques including emulsification, solvent diffusion, DNA
      complexation, and entrapment. The diversity of formulation strategies presented
      is a testament to the exponential growth and interest in the area of vaccine
      delivery systems. A case study for the application of particulate vaccine
      carriers is assessed in terms of vaccine development and recent insights into the
      possible design and application of vaccines against two of the most important
      pathogens that threaten mankind and for which there is a significant need:
      Mycobacterium tuberculosis and human immunodeficiency virus. This review
      addresses the rationale for the use of particulate delivery systems in vaccine
      design in the context of the diversity of carriers for DNA- and protein-based
      vaccines and their potential for application in terms of the critical need for
      effective vaccines.

PMID- 15862112
TI  - The iron-siderophore transporter FhuA is the receptor for the antimicrobial
      peptide microcin J25: role of the microcin Val11-Pro16 beta-hairpin region in the
      recognition mechanism.
AB  - The role of the outer-membrane iron transporter FhuA as a potential receptor for
      the antimicrobial peptide MccJ25 (microcin J25) was studied through a series of
      in vivo and in vitro experiments. The requirement for both FhuA and the inner
      membrane TonB-ExbB-ExbD complex was demonstrated by antibacterial assays using
      complementation of an fhuA(-) strain and by using isogenic strains mutated in
      genes encoding the protein complex respectively. In addition, MccJ25 was shown to
      block phage T5 infection of Escherichia coli, in vivo, by inhibiting phage
      adhesion, which suggested that MccJ25 prevents the interaction between the phage
      and its receptor FhuA. This in vivo activity was confirmed in vitro, as MccJ25
      inhibited phage T5 DNA ejection triggered by purified FhuA. Direct interaction of
      MccJ25 with FhuA was demonstrated for the first time by size-exclusion
      chromatography and isothermal titration calorimetry. MccJ25 bound to FhuA with a
      2:1 stoichiometry and a K(d) of 1.2 microM. Taken together, our results
      demonstrate that FhuA is the receptor for MccJ25 and that the ligand-receptor
      interaction may occur in the absence of other components of the bacterial
      membrane. Finally, both differential scanning calorimetry and antimicrobial
      assays showed that MccJ25 binding involves external loops of FhuA. Unlike native
      MccJ25, a thermolysin-cleaved MccJ25 variant was unable to bind to FhuA and
      failed to prevent phage T5 infection of E. coli. Therefore the Val11-Pro16 beta
      hairpin region of MccJ25, which is disrupted upon cleavage by thermolysin, is
      required for microcin recognition.

PMID- 15862113
TI  - Relative contribution of PDX-1, MafA and E47/beta2 to the regulation of the human
      insulin promoter.
AB  - The insulin promoter binds a number of tissue-specific and ubiquitous
      transcription factors. Of these, the homoeodomain protein PDX-1 (pancreatic
      duodenal homeobox factor-1), the basic leucine zipper protein MafA and the basic
      helix-loop-helix heterodimer E47/BETA2 (beta-cell E box transactivator 2;
      referred to here as beta2) bind to important regulatory sites. Previous studies
      have shown that PDX-1 can interact synergistically with E47 and beta2 to activate
      the rat insulin 1 promoter. The aim of the present study was to determine the
      relative contribution of PDX-1, MafA and E47/beta2 in regulating the human
      insulin promoter, and whether these factors could interact synergistically in the
      context of the human promoter. Mutagenesis of the PDX-1, MafA and E47/beta2
      binding sites reduced promoter activity by 60, 74 and 94% respectively, in INS-1
      beta-cells. In the islet glucagonoma cell line alphaTC1.6, overexpression of PDX
      1 and MafA separately increased promoter activity approx. 2.5-3-fold, and in
      combination approx. 6-fold, indicating that their overall effect was additive.
      Overexpression of E47 and beta2 had no effect. In HeLa cells, PDX-1 stimulated
      the basal promoter by approx. 40-fold, whereas MafA, E47 and beta2 each increased
      activity by less than 2-fold. There was no indication of any synergistic effects
      on the human insulin promoter. On the other hand, the rat insulin 1 promoter and
      a mutated version of the human insulin promoter, in which the relevant regulatory
      elements were separated by the same distances as in the rat insulin 1 promoter,
      did exhibit synergy. PDX-1 was shown further to activate the endogenous insulin 1
      gene in alphaTC1.6 cells, whereas MafA activated the insulin 2 gene. In
      combination, PDX-1 and MafA activated both insulin genes. Chromatin
      immunoprecipitation assays confirmed that PDX-1 increased the association of
      acetylated histones H3 and H4 with the insulin 1 gene and MafA increased the
      association of acetylated histone H3 with the insulin 2 gene.

PMID- 15862114
TI  - Roles of 14-3-3 and calmodulin binding in subcellular localization and function
      of the small G-protein Rem2.
AB  - kir/Gem, Rad, Rem and Rem2 comprise the RGK (Rad/Gem/kir) family of Ras-related
      small G-proteins. Two important functions of RGK proteins are the regulation of
      the VDCC (voltage-dependent Ca2+ channel) activity and cell-shape remodelling.
      RGK proteins interact with 14-3-3 and CaM (calmodulin), but their role on RGK
      protein function is poorly understood. In contrast with the other RGK family
      members, Rem2 has been reported to bind neither 14-3-3 nor induce membrane
      extensions. Furthermore, although Rem2 inhibits VDCC activity, it does not
      prevent cell-surface transport of Ca2+ channels as has been shown for kir/Gem. In
      the present study, we re-examined the functions of Rem2 and its interaction with
      14-3-3 and CaM. We show that Rem2 in fact does interact with 14-3-3 and CaM and
      induces dendrite-like extensions in COS cells. 14-3-3, together with CaM,
      regulates the subcellular distribution of Rem2 between the cytoplasm and the
      nucleus. Rem2 also interacts with the beta-subunits of VDCCs in a GTP-dependent
      fashion and inhibits Ca2+ channel activity by blocking the alpha-subunit
      expression at the cell surface. Thus Rem2 shares many previously unrecognized
      features with the other RGK family members.

PMID- 15862115
TI  - Proteomics reveals that proteins expressed during the early stage of Bacillus
      anthracis infection are potential targets for the development of vaccines and
      drugs.
AB  - In this review, we advance a new concept in developing vaccines and/or drugs to
      target specific proteins expressed during the early stage of Bacillus anthracis
      (anthrax) infection and address existing challenges to this concept. Three
      proteins (immune inhibitor A, GPR-like spore protease, and alanine racemase)
      initially identified by proteomics in our laboratory were found to have
      differential expressions during anthrax spore germination and early outgrowth.
      Other studies of different bacillus strains indicate that these three proteins
      are involved in either germination or cytotoxicity of spores, suggesting that
      they may serve as potential targets for the design of anti-anthrax vaccines and
      drugs.

PMID- 15862117
TI  - Identification of protein coding regions of rice genes using alternative spectral
      rotation measure and linear discriminant analysis.
AB  - An improved method, called Alternative Spectral Rotation (ASR) measure, for
      predicting protein coding regions in rice DNA has been developed. The method is
      based on the Spectral Rotation (SR) measure proposed by Kotlar and Lavner, and
      its accuracy is higher than that of the SR measure and the Spectral Content (SC)
      measure proposed by Tiwari et al. In order to increase the identifying accuracy,
      we chose three different coding characters, namely the asymmetric, purine, and
      stop-codon variables as parameters, and an approving result was presented by the
      method of Linear Discriminant Analysis (LDA).

PMID- 15862116
TI  - Application of proteomics in the study of tumor metastasis.
AB  - Tumor metastasis is the dominant cause of death in cancer patients. However, the
      molecular and cellular mechanisms underlying tumor metastasis are still elusive.
      The identification of protein molecules with their expressions correlated to the
      metastatic process would help to understand the metastatic mechanisms and thus
      facilitate the development of strategies for the therapeutic interventions and
      clinical management of cancer. Proteomics is a systematic research approach
      aiming to provide the global characterization of protein expression and function
      under given conditions. Proteomic technology has been widely used in biomarker
      discovery and pathogenetic studies including tumor metastasis. This article
      provides a brief review of the application of proteomics in identifying molecular
      factors in tumor metastasis process. The combination of proteomics with other
      experimental approaches in biochemistry, cell biology, molecular genetics and
      chemistry, together with the development of new technologies and improvements in
      existing methodologies will continue to extend its application in studying cancer
      metastasis.

PMID- 15862118
TI  - A systematical analysis of tryptic peptide identification with reverse phase
      liquid chromatography and electrospray ion trap mass spectrometry.
AB  - In this study we systematically analyzed the elution condition of tryptic
      peptides and the characteristics of identified peptides in reverse phase liquid
      chromatography and electrospray tandem mass spectrometry (RPLC-MS/MS) analysis.
      Following protein digestion with trypsin, the peptide mixture was analyzed by on
      line RPLC-MS/MS. Bovine serum albumin (BSA) was used to optimize acetonitrile
      (ACN) elution gradient for tryptic peptides, and Cytochrome C was used to retest
      the gradient and the sensitivity of LC-MS/MS. The characteristics of identified
      peptides were also analyzed. In our experiments, the suitable ACN gradient is 5%
      to 30% for tryptic peptide elution and the sensitivity of LC-MS/MS is 50 fmol.
      Analysis of the tryptic peptides demonstrated that longer (more than 10 amino
      acids) and multi-charge state (+2, +3) peptides are likely to be identified, and
      the hydropathicity of the peptides might not be related to whether it is more
      likely to be identified or not. The number of identified peptides for a protein
      might be used to estimate its loading amount under the same sample background.
      Moreover, in this study the identified peptides present three types of
      redundancy, namely identification, charge, and sequence redundancy, which may
      repress low abundance protein identification.

PMID- 15862119
TI  - A novel algorithm for finding interspersed repeat regions.
AB  - The analysis of repeats in the DNA sequences is an important subject in
      bioinformatics. In this paper, we propose a novel projection-assemble algorithm
      to find unknown interspersed repeats in DNA sequences. The algorithm employs
      random projection algorithm to obtain a candidate fragment set, and exhaustive
      search algorithm to search each pair of fragments from the candidate fragment set
      to find potential linkage, and then assemble them together. The complexity of our
      projection-assemble algorithm is nearly linear to the length of the genome
      sequence, and its memory usage is limited by the hardware. We tested our
      algorithm with both simulated data and real biology data, and the results show
      that our projection-assemble algorithm is efficient. By means of this algorithm,
      we found an un-labeled repeat region that occurs five times in Escherichia coli
      genome, with its length more than 5,000 bp, and a mismatch probability less than
      4%.

PMID- 15862121
TI  - Timeline of genomics (1951-1976).

PMID- 15862120
TI  - SeeDNA: a visualization tool for K-string content of long DNA sequences and their
      randomized counterparts.
AB  - An interactive tool to visualize the K-string composition of long DNA sequences
      including bacterial complete genomes is described. It is especially useful for
      exploring short palindromic structures in the sequences. The SeeDNA program runs
      on Red Hat Linux with GTK+ support. It displays two-dimensional (2D) or one
      dimensional (1D) histograms of the K-string distribution of a given sequence
      and/or its randomized counterpart. It is also capable of showing the difference
      of K-string distributions between two sequences. The C source code using the GTK+
      package is freely available.

PMID- 15862122
TI  - Adapting developing country epidemiological assessment techniques to improve the
      quality of health needs assessments in developed countries.
AB  - BACKGROUND: We were commissioned to carry out three health assessments in urban
      areas of Dublin in Ireland. We required an epidemiologically robust method that
      could collect data rapidly and inexpensively. We were dealing with inadequate
      health information systems, weak planning data and a history of inadequate
      recipient involvement in health service planning. These problems had also been
      identified by researchers carrying out health assessments in developing
      countries. This paper reports our experience of adapting a cluster survey model
      originally developed by international organisations to assess community health
      needs and service coverage in developing countries and applying our adapted model
      to three urban areas in Dublin, Ireland METHODS: We adapted the model to control
      for socio-economic heterogeneity, to take account of the inadequate population
      list, to ensure a representative sample and to account for a higher prevalence of
      degenerative and chronic diseases. We employed formal as well as informal
      communication methods and adjusted data collection times to maximise
      participation. RESULTS: The model we adapted had the capacity to ascertain both
      health needs and health care delivery needs. The community participated
      throughout the process and members were trained and employed as data collectors.
      The assessments have been used by local health boards and non-governmental
      agencies to plan and deliver better or additional services. CONCLUSION: We were
      able to carry out high quality health needs assessments in urban areas by
      adapting and applying a developing country health assessment method. Issues arose
      relating to health needs assessment as part of the planning cycle and the role of
      participants in the process.

PMID- 15862123
TI  - Inflammatory myofibroblastic tumour of the gallbladder.
AB  - BACKGROUND: Inflammatory myofibroblastic tumour (IMT) is a benign,
      nonmetastasizing proliferation of myofibroblasts with a potential for local
      infiltration, recurrence and persistent local growth. CASE REPORT: We report a
      case of a 51 year-old female, who had excision of a gallbladder tumour.
      Histopathology showed it to be IMT of the gallbladder. CONCLUSION: The approach
      to these tumours should be primarily surgical resection to obtain a definitive
      diagnosis and relieve symptoms. IMT has a potential for local infiltration,
      recurrence and persistent local growth.

PMID- 15862124
TI  - Assessing subgroup effects with binary data: can the use of different effect
      measures lead to different conclusions?
AB  - BACKGROUND: In order to use the results of a randomised trial, it is necessary to
      understand whether the overall observed benefit or harm applies to all
      individuals, or whether some subgroups receive more benefit or harm than others.
      This decision is commonly guided by a statistical test for interaction. However,
      with binary outcomes, different effect measures yield different interaction
      tests. For example, the UK Hip trial explored the impact of ultrasound of infants
      with suspected hip dysplasia on the occurrence of subsequent hip treatment. Risk
      ratios were similar between subgroups defined by level of clinical suspicion (P =
      0.14), but odds ratios and risk differences differed strongly between subgroups
      (P < 0.001). DISCUSSION: Interaction tests on different effect measures differ
      because they test different null hypotheses. A graphical technique demonstrates
      that the difference arises when the subgroup risks differ markedly. We consider
      that the test of interaction acts as a check on the applicability of the trial
      results to all included subgroups. The test of interaction should therefore be
      applied to the effect measure which is least likely a priori to exhibit an
      interaction. We give examples of how this might be done. SUMMARY: The choice of
      interaction test is especially important when the risk of a binary outcome varies
      widely between subgroups. The interaction test should be pre-specified and should
      be guided by clinical knowledge.

PMID- 15862125
TI  - Optimal search strategies for identifying sound clinical prediction studies in
      EMBASE.
AB  - BACKGROUND: Clinical prediction guides assist clinicians by pointing to specific
      elements of the patient's clinical presentation that should be considered when
      forming a diagnosis, prognosis or judgment regarding treatment outcome. The
      numbers of validated clinical prediction guides are growing in the medical
      literature, but their retrieval from large biomedical databases remains
      problematic and this presents a barrier to their uptake in medical practice. We
      undertook the systematic development of search strategies ("hedges") for
      retrieval of empirically tested clinical prediction guides from EMBASE. METHODS:
      An analytic survey was conducted, testing the retrieval performance of search
      strategies run in EMBASE against the gold standard of hand searching, using a
      sample of all 27,769 articles identified in 55 journals for the 2000 publishing
      year. All articles were categorized as original studies, review articles, general
      papers, or case reports. The original and review articles were then tagged as
      'pass' or 'fail' for methodologic rigor in the areas of clinical prediction
      guides and other clinical topics. Search terms that depicted clinical prediction
      guides were selected from a pool of index terms and text words gathered in house
      and through request to clinicians, librarians and professional searchers. A total
      of 36,232 search strategies composed of single and multiple term phrases were
      trialed for retrieval of clinical prediction studies. The sensitivity,
      specificity, precision, and accuracy of search strategies were calculated to
      identify which were the best. RESULTS: 163 clinical prediction studies were
      identified, of which 69 (42.3%) passed criteria for scientific merit. A 3-term
      strategy optimized sensitivity at 91.3% and specificity at 90.2%. Higher
      sensitivity (97.1%) was reached with a different 3-term strategy, but with a 16%
      drop in specificity. The best measure of specificity (98.8%) was found in a 2
      term strategy, but with a considerable fall in sensitivity to 60.9%. All single
      term strategies performed less well than 2- and 3-term strategies. CONCLUSION:
      The retrieval of sound clinical prediction studies from EMBASE is supported by
      several search strategies.

PMID- 15862126
TI  - Progress and controversies in developing cancer vaccines.
AB  - Immunotherapy has become a standard approach for cancer management, through the
      use of cytokines (eg: interleukin-2) and monoclonal antibodies. Cancer vaccines
      hold promise as another form of immunotherapy, and there has been substantial
      progress in identifying shared antigens recognized by T cells, in developing
      vaccine approaches that induce antigen-specific T cell responses in cancer
      patients, and in developing new technology for monitoring immune responses in
      various human tissue compartments. Dramatic clinical regressions of human solid
      tumors have occurred with some cancer vaccines, but the rate of those responses
      remains low. This article is part of a 2-part point:counterpoint series on
      peptide vaccines and adoptive therapy approaches for cancer. The current status
      of cancer vaccination, and associated challenges, are discussed. Emphasis is
      placed on the need to increase our knowledge of cancer immunobiology, as well as
      to improve monitoring of cellular immune function after vaccination. Progress in
      both areas will facilitate development of effective cancer vaccines, as well as
      of adoptive therapy. Effective cancer vaccines promise to be useful for treatment
      and prevention of cancer at low cost and with low morbidity.

PMID- 15862128
TI  - Stage-specific expression of the mitochondrial co-chaperonin of Leishmania
      donovani, CPN10.
AB  - BACKGROUND: Leishmania spp., in the course of their parasitic life cycle,
      encounter two vastly different environments: the gut of sandflies and the
      phagosomes of mammalian macrophages. During transmission into a mammal, the
      parasites are exposed to increased ambient temperature as well as to different
      carbon sources. Molecular chaperones or heat shock proteins are implicated in the
      necessary adaptations which involve the ordered differentiation from the
      flagellated, extracellular promastigote to the intracellular amastigote stage.
      RESULTS: Here, we show that the Leishmania donovani co-chaperonin, CPN10, is
      synthesised to a significantly increased concentration during in vitro
      differentiation to the amastigote stage. We show by fluorescence microscopy and
      by immunogold electron microscopy that, like its putative complex partner
      CPN60.2, CPN10 is localised to the single, tubular mitochondrion of the parasites
      and, moreover, that it co-precipitates with CPN60.2, the major mitochondrial
      chaperonin of Leishmania spp.. CONCLUSION: Our data indicate an increased
      requirement for CPN10 in the context of mitochondrial protein folding during or
      early in the mammalian stage of this pathogen. Moreover, they confirm the CPN60.2
      as bona fide mitochondrial GroEL homologue in L. donovani and the postulated
      interaction of eukaryotic chaperonins, CPN60 and CPN10.

PMID- 15862127
TI  - A phase I study of hydralazine to demethylate and reactivate the expression of
      tumor suppressor genes.
AB  - BACKGROUND: The antihypertensive compound hydralazine is a known demethylating
      agent. This phase I study evaluated the tolerability and its effects upon DNA
      methylation and gene reactivation in patients with untreated cervical cancer.
      METHODS: Hydralazine was administered to cohorts of 4 patients at the following
      dose levels: I) 50 mg/day, II) 75 mg/day, III) 100 mg/day and IV) 150 mg/day.
      Tumor biopsies and peripheral blood samples were taken the day before and after
      treatment. The genes APC, MGMT; ER, GSTP1, DAPK, RARbeta, FHIT and p16 were
      evaluated pre and post-treatment for DNA promoter methylation and gene expression
      by MSP (Methylation-Specific PCR) and RT-PCR respectively in each of the tumor
      samples. Methylation of the imprinted H19 gene and the "normally methylated"
      sequence clone 1.2 was also analyzed. Global DNA methylation was analyzed by
      capillary electrophoresis and cytosine extension assay. Toxicity was evaluated
      using the NCI Common Toxicity Criteria. RESULTS: Hydralazine was well tolerated.
      Toxicities were mild being the most common nausea, dizziness, fatigue, headache
      and palpitations. Overall, 70% of the pretreatment samples and all the patients
      had at least one methylated gene. Rates of demethylation at the different dose
      levels were as follows: 50 mg/day, 40%; 75 mg/day, 52%, 100 mg/day, 43%, and 150
      mg/day, 32%. Gene expression analysis showed only 12 informative cases, of these
      9 (75%) re-expressed the gene. There was neither change in the methylation status
      of H19 and clone 1.2 nor changes in global DNA methylation. CONCLUSION:
      Hydralazine at doses between 50 and 150 mg/day is well tolerated and effective to
      demethylate and reactivate the expression of tumor suppressor genes without
      affecting global DNA methylation.

PMID- 15862129
TI  - A novel EB-1/AIDA-1 isoform, AIDA-1c, interacts with the Cajal body protein
      coilin.
AB  - BACKGROUND: Cajal bodies (CBs) are nuclear suborganelles that play a role in the
      biogenesis of small nuclear ribonucleoproteins (snRNPs), which are crucial for
      pre-mRNA splicing. Upon nuclear reentry, Sm-class snRNPs localize first to the
      CB, where the snRNA moiety of the snRNP is modified. It is not clear how snRNPs
      target to the CB and are released from this structure after their modification.
      Coilin, the CB marker protein, may participate in snRNP biogenesis given that it
      can interact with snRNPs and SMN. SMN is crucial for snRNP assembly and is the
      protein mutated in the neurodegenerative disease Spinal Muscular Atrophy. Coilin
      knockout mice display significant viability problems and altered CB formation.
      Thus characterization of the CB and its associated proteins will give insight
      into snRNP biogenesis and clarify the dynamic organization of the nucleus.
      RESULTS: In this report, we identify a novel protein isoform of EB-1/AIDA-1,
      termed AIDA-1c, that interacts with the CB marker protein, coilin. Northern and
      nested PCR experiments reveal that the AIDA-1c isoform is expressed in brain and
      several cancer cell lines. Competition binding experiments demonstrate that AIDA
      1c competes with SmB' for coilin binding sites, but does not bind SMN. When
      ectopically expressed, AIDA-1c is predominantly nuclear with no obvious
      accumulations in CBs. Interestingly, another EB-1/AIDA-1 nuclear isoform, AIDA
      1a, does not bind coilin in vivo as efficiently as AIDA-1c. Knockdown of EB
      1/AIDA-1 isoforms by siRNA altered Cajal body organization and reduced cell
      viability. CONCLUSION: These data suggest that specific EB-1/AIDA-1 isoforms,
      such as AIDA-1c, may participate in the regulation of nucleoplasmic coilin
      protein interactions in neuronal and transformed cells.

PMID- 15862130
TI  - The not-for-profit form and translational research: Kerr revisited?
AB  - Translational research conducted in academic health centers is confounded by the
      organizational structure in which the work is performed. Investigators must
      obtain research funding and appropriate recognition as a part of a research team
      in a not-for-profit environment which has more readily rewarded basic work, and
      individual accomplishments. What results is a unique form of conflict of
      interest, best understood by relating the basic principles underlying the not-for
      profit form to the conduct of translational research in the AHC setting.

PMID- 15862131
TI  - A portable near infrared spectroscopy system for bedside monitoring of newborn
      brain.
AB  - BACKGROUND: Newborns with critical health conditions are monitored in neonatal
      intensive care units (NICU). In NICU, one of the most important problems that
      they face is the risk of brain injury. There is a need for continuous monitoring
      of newborn's brain function to prevent any potential brain injury. This type of
      monitoring should not interfere with intensive care of the newborn. Therefore, it
      should be non-invasive and portable. METHODS: In this paper, a low-cost, battery
      operated, dual wavelength, continuous wave near infrared spectroscopy system for
      continuous bedside hemodynamic monitoring of neonatal brain is presented. The
      system has been designed to optimize SNR by optimizing the wavelength
      multiplexing parameters with special emphasis on safety issues concerning burn
      injuries. SNR improvement by utilizing the entire dynamic range has been
      satisfied with modifications in analog circuitry. RESULTS AND CONCLUSION: As a
      result, a shot-limited SNR of 67 dB has been achieved for 10 Hz temporal
      resolution. The system can operate more than 30 hours without recharging when an
      off-the-shelf 1850 mAh-7.2 V battery is used. Laboratory tests with optical
      phantoms and preliminary data recorded in NICU demonstrate the potential of the
      system as a reliable clinical tool to be employed in the bedside regional
      monitoring of newborn brain metabolism under intensive care.

PMID- 15862132
TI  - APF, HB-EGF, and EGF biomarkers in patients with ulcerative vs. non-ulcerative
      interstitial cystitis.
AB  - BACKGROUND: Interstitial cystitis (IC) is a chronic bladder disorder, with
      symptoms including pelvic and or perineal pain, urinary frequency, and urgency.
      The etiology of IC is unknown, but sensitive and specific biomarkers have been
      described, including antiproliferative factor (APF), heparin-binding epidermal
      growth factor-like growth factor (HB-EGF), and epidermal growth factor (EGF).
      However, the relative sensitivity of these biomarkers in ulcerative vs.
      nonulcerative IC is unknown, and these markers have yet to be validated in
      another laboratory. We therefore measured these markers in urine from patients
      with or without Hunner's ulcer, as well as normal controls, patients with bladder
      cancer, and patients with bacterial cystitis, at the First Hospital of China
      Medical University. METHODS: Urine specimens were collected from two groups of
      Chinese IC patients (38 IC patients with Hunner's ulcers, 26 IC patients without
      Hunner's ulcers), 30 normal controls, 10 bacterial cystitis patients and 10
      bladder cancer patients. APF activity was determined by measuring 3H-thymidine
      incorporation in vitro, and HB-EGF and EGF levels were determined by ELISA.
      RESULTS: APF activity (inhibition of thymidine incorporation) was significantly
      greater in all IC patient urine specimens than in normal control specimens or in
      specimens from patients with bacterial cystitis or bladder cancer (p < 0.0001 for
      each comparison). Urine HB-EGF levels were also significantly lower and EGF
      levels significantly higher in both groups of IC patients than in the three
      control groups (p < 0.0001 for each comparison). Although APF and HB-EGF levels
      were similar in ulcerative and nonulcerative IC patients, EGF levels were
      significantly higher in IC patients with vs. without ulcers (p < 0.004).
      CONCLUSION: These findings indicate that APF, HB-EGF and EGF are good biomarkers
      for both ulcerative and nonulcerative IC and validate their measurement as
      biomarkers for IC in Chinese patients.

PMID- 15862134
TI  - Hypoxia-induced adaptational shift in MHC-beta isoform expression in rat
      ventricles.
AB  - We investigated whether the shift of cardiac myosin heavy chain (MHC) isoform
      observed during exposure to hypoxia is secondary to hypertrophy, or whether it is
      directly related to the hypoxic stress. Twelve male Wistar-Kyoto rats, 14 weeks
      old, were randomly assigned to two groups: sea-level control group (CO) and
      hypoxia group (HX). The CO group was housed 4 weeks at 1,011 hPa, and the HX
      group was housed for 4 weeks at 701 hPa. The expression of MHC-beta was
      significantly increased (600%) in the HX group as compared to the CO group in the
      right ventricle (p < 0.01). An increased ventricular mass induced by hypoxic
      exposure was associated with an increased expression of MHC-beta in the right
      ventricle (p < 0.05). In the left ventricle, the MHC-b expression was
      significantly increased (295%) in the HX group as compared to the CO group
      without ventricular hypertrophy (p < 0.01). No differences were observed in the
      adenylyl cyclase activity or in the phosphodiesterase activities in both
      ventricles between the CO and HX groups (p > 0.05). Oxidative enzymatic
      activities (citrate synthase and three-hydroxyacyl-CoA dehydrogenase) were
      unchanged in both ventricles following 4 weeks of hypoxia (p > 0.05). These
      findings suggest that, besides cardiac hypertrophy, the hypoxia-induced
      adaptational change to the MHC-b isoform may be mediated through a specific
      mechanism related to the stress of hypoxia.

PMID- 15862133
TI  - Oxidative stress and the use of antioxidants in diabetes: linking basic science
      to clinical practice.
AB  - Cardiovascular complications, characterized by endothelial dysfunction and
      accelerated atherosclerosis, are the leading cause of morbidity and mortality
      associated with diabetes. There is growing evidence that excess generation of
      highly reactive free radicals, largely due to hyperglycemia, causes oxidative
      stress, which further exacerbates the development and progression of diabetes and
      its complications. Overproduction and/or insufficient removal of these free
      radicals result in vascular dysfunction, damage to cellular proteins, membrane
      lipids and nucleic acids. Despite overwhelming evidence on the damaging
      consequences of oxidative stress and its role in experimental diabetes, large
      scale clinical trials with classic antioxidants failed to demonstrate any benefit
      for diabetic patients. As our understanding of the mechanisms of free radical
      generation evolves, it is becoming clear that rather than merely scavenging
      reactive radicals, a more comprehensive approach aimed at preventing the
      generation of these reactive species as well as scavenging may prove more
      beneficial. Therefore, new strategies with classic as well as new antioxidants
      should be implemented in the treatment of diabetes.

PMID- 15862135
TI  - [In vitro refolding and functional study of soluble HLA-G1-peptide complex].
AB  - AIM: To form soluble HLA-G1-peptide complex by refolding in vitro, and to study
      its immune function. METHODS: The heavy chain and beta(2m) of sHLA-G1 were
      expressed as insoluble aggregates in E. coli, and then the two subunits were
      refolded to form HLA-G1-peptide complex by dilution method in the presence of
      specific peptide. The refolded product was purified through Sephadex G-75 gel
      filtration. The purified product was identified by Western blot with mAb W6/32.
      The function of soluble HLA-G1 was explored from following three aspects, namely,
      the influences on cytotoxicity of NK cells, on proliferation of T cells in mixed
      lymphocyte culture and apoptosis of activated T cells. RESULTS: The refolded
      complex was recognized by mAb W6/32. It effectively inhibited cytotoxicity of NK
      cells and proliferation of T cells, and induced apoptosis of activated T cells.
      CONCLUSION: The refolding of soluble HLA-G1-peptide complex has been successfully
      realized in vitro. The complex can inhibit the functions of NK cells and T cells.

PMID- 15862136
TI  - [Expression, purification, and characterization of single-chain disulfide-bond Fv
      (ScdsFv) antibody fused with targeted superantigen SEA (D227A)].
AB  - AIM: To express, purify, and characterize scdsFv antibody fused with superantigen
      SEA(D227A). METHODS: The expression plasmid of scdsFv-SEA(D227A) was constructed
      by standard molecular cloning procedures. The recombinant protein was induced to
      express in E. coli BL21plusS by IPTG and purified by Q Sepharose HP column and
      Hiprep 26/60 Sephacryl S-200 HR column. Formation of the intramolecular disulfide
      bond of the purified protein was analysed by AMS alkylation and PAGE
      electrophoresis. The binding activity, stability and killing activity of the
      purified protein were assayed by ELISA and MTS, respectively. RESULTS: The
      recombinant protein was expressed as inclusion body, accounting for more than 30%
      of total bacterial protein. After purification by Q Sepharose HP and Hiprep 26/60
      Sephacryl S-200 HR, the yield of the purified protein was 60 mg per liter of
      induced culture. AMS alkylation and PAGE electrophoresis analysis showed that
      intramolecular disulfide bond formed correctly in the recombinant protein. The
      purified protein had similar binding affinity as dsFv fused SEA and scFv fused
      SEA have and similar killing activity as native SEA has to human hepatoma cell
      line, but more stable, in vitro, as compared with dsFv fused SEA and scFv fused
      with SEA. CONCLUSION: The scdsFv fused with SEA, as a novel form of immunotoxin,
      might be used in cancer treatment.

PMID- 15862137
TI  - [Construction of recombinant expression vector of IL-24 gene and prokaryotic
      expression].
AB  - AIM: To construct a recombinant expression vector of human IL-24 gene and express
      it in E. coli. METHODS: The hIL-24 cDNA fragment was amplified from plasmid TRAP
      hIL-24 by PCR, then cloned into the prokaryotic vector pGEX-KG, and expressed as
      a fusion protein in E. coli. The expressed IL-24-GST fusion protein was purified
      via GST-Sepharose 4B Column and identified by SDS-PAGE and Western blot. The
      bioactivity of GST-IL-24 fusion protein was measured by MTT assay. RESULTS:
      Restriction enzyme digestion analysis showed that the recombinant prokaryotic
      expression vector pGEX-KG-IL-24 was successfully constructed and expressed in E.
      coli. The relative molecular mass (M(r)) of the expression product was identical
      with the predicted value. The proliferation of THP-1 cells was inhibited by GST
      IL-24 fusion protein. CONCLUSION: The recombinant expression vector pGEX-KG-IL-24
      has been constructed successfully and expressed as a bioactive fusion protein in
      E. coli BL21 (BlysS), which is helpful for the further study of the biological
      function of IL-24.

PMID- 15862138
TI  - [Regulation of soluble TRAIL and membrane TRAIL in Jurkat cells by PMA].
AB  - AIM: To investigate the regulation of soluble and membrane bound TNF-related
      apoptosis-inducing ligand (TRAIL) in Jurkt cells by phorbol myristic acctate
      (PMA), and the cytotoxicity of the two forms of TRAIL. METHODS: Jurkat cells were
      cultured in the presence of 40 ng/mL PMA for different time. The production of
      sTRAIL was determined by ELISA, and expression of mTRAIL was analyzed by indirect
      fluorescence staining and flow cytometry analysis. The cytotoxicites of sTRAIL
      and mTRAIL were detected by (51)Cr release assay, in which DR4/DR5-expressing
      Raji cells were employed as target cells. RESULTS: The expression of both sTRAIL
      and mTRAIL in Jurkat cells were upregulated by PMA. The level of sTRAIL in
      supernatant from PMA-stimulated Jurkat cell culture increased and reached peak at
      48 hours after PMA treatment, whereas expression peak of mTRAIL was at 60 hours.
      Both sTRAIL and mTRAIL exhibited cytotoxicity against Raji cells. CONCLUSION:
      PMA, a PKC activator, can upregulate the expression of both sTRAIL and mTRAIL in
      Jurkat cells, and the two forms of TRAIL have cytotoxic activity.

PMID- 15862139
TI  - [Expression and purification of two kinds of alternative splicing mouse Era].
AB  - AIM: To express and purify two alternative splicing mouse Era proteins and detect
      whether anti-human Era antibody can be used in the study of mouse Era proteins.
      METHODS: Two fusion protein expression vectors, pMAL-meraW and pMAL-meraS, were
      constructed, then the MBP-mEra proteins were expressed in E. coli. The target
      proteins were purified by amylose affinity chromatography. The specificity of
      rabbit anti-human Era antibody to the proteins was identified by Western blot.
      RESULTS: The expressed MBP-mEraW and MBP-mEraS proteins constituted approximately
      17% and 19% of the total bacterial proteins. The purity of the fused proteins was
      67% and 61% respectively after amylose affinity chromatography. Rabbit anti-human
      Era antibody had high specificity to these two kinds of splicing mouse Era
      proteins. CONCLUSION: Two fusion mera genes could be expressed in E. coli by
      using gene recombination technique. The high specificity of rabbit anti-human Era
      antibody to the two splicing mouse ERA proteins indicates that this antibody can
      be used to study the function of these two kinds of splicing mouse Era.

PMID- 15862140
TI  - [Expression and purification of rat betacellulin with biological activity].
AB  - AIM: To obtain recombinant rat betacellulin with biological activity. METHODS: A
      534 bp of rat betacellulin gene fragment was amplified by RT-PCR from rat kidney
      and cloned into pET28a(+) vector to construct recombinant plasmid pET28a-rBTC.
      The recombinant plasmid was transformed into E. coli BL-21(DE3) and the
      betacellulin was expressed under IPTG induction. The expressed betacellulin was
      detected by SDS-PAGE and Western blot. The expressed protein was purified by
      Ni(2+) affinity chromatography and then renatured by dialysis. The effect of the
      renatured protein on proliferation of NIH3T3 cells was detected by MTT
      colorimetry. RESULTS: Rat betacellulin protein with M(r) being 20 000 was
      expressed under IPTG induction. The purity of purified protein reached over 96%.
      After renaturation, the expressed protein could significantly stimulate the
      proliferation of NIH3T3 cells. CONCLUSION: Rat betacellulin gene is successfully
      cloned into the expression vector pET28a(+) and highly expressed in E.coli.
      Purified and refolded betacellulin protein can obviously stimulate the
      proliferation of NIH3T3 cells.

PMID- 15862141
TI  - [The effects of rBCG expressing Der p2 in the form of lipoprotein on murine
      immune response].
AB  - AIM: To investigate the effects of rBCG vaccination containing foreign antigen
      Der p2 in the form of lipoprotein on murine immune response. METHODS: 6 to 8
      weeks old and newborn BALB/c mice were vaccined intraperitoneally with 10(6) CFU
      rBCG or BCG. At the same time, the control group was injected with saline. Six
      weeks later, all animals were injected with Der p2 (20 microg). After two weeks
      later, the concentrations of IL-4 and IFN-gamma in the serum and splenocyte
      culture supernatant (STLCS) were determined by ELISA, and Th subgroups were
      determined by double fluorescent staining and flow cytometry. RESULTS: After
      vaccination, the serum and STLCS from both rBCG-immunized and BCG-immunized group
      of adult and newborn BALB/c mice had significantly higher level of IFN-gamma and
      lower level of IL-4 than those from control groups. Besides, there was the larger
      percentage of CD4 (+) IFN-gamma (+) cells in spleen from rBCG-vaccined and BCG
      vaccined mice than that from control group. However, the percentage of CD4 (+) IL
      4 (+) cells in spleen cells from rBCG-vaccined and BCG-vaccined group was lower
      than that from control group. Moreover, the level of IFN-gamma in STLCS from rBCG
      immunized was significantly higher, compared with that from BCG-immunized mice.
      At the same time, the percentage of CD4 (+) IFN-gamma (+) cells in spleen from
      rBCG-vaccined mice was larger than that from BCG-vaccined group. CONCLUSION: Both
      rBCG and BCG could stimulate Th1 predominant immune response, when injected
      intraperitoneally into adult or newborn BALB/c mice, The Der p2 expressed on the
      cell wall of BCG can work as the component of BCG and be recognized by the immune
      system of mice, therefore stimulates Der p2-specific Th1 predominant immune
      response. These data indicate that recombinant BCG-expressing antigens can be
      used as the antigen-specific vaccines against allergic diseases by regulating the
      balance of Th1/Th2.

PMID- 15862142
TI  - [A preliminary study of CTGF in bleomycin-induced mouse pulmonary fibrosis].
AB  - AIM: To investigate CTGF's role in bleomycin-induced pulmonary fibrosis. METHODS:
      Kunming mice were intratracheally administered with bleomycin to establish
      pulmonary fibrosis model. The expression of CTGF was studied by
      immunohistochemical method and RT-PCR. The degree of fibrosis was evaluated by
      pulmonary hydroxyproline assay. RESULTS: CTGF protein and mRNA were not expressed
      in normal mice. However, they were detected in pulmonary fibrotic mice from day 7
      after bleomycin treatment, and increased as fibrosis developed (P <0.01). CTGF
      protein's expression was correlated with hydroxyproline content in lung tissue
      (r=0.92, P <0.01). CONCLUSION: CTGF plays a role in pulmonary fibrosis. Detection
      of CTGF may be an early and sensitive marker for evaluating the occurrence and
      development of pulmonary fibrosis.

PMID- 15862143
TI  - [Expressions of IL-18Ralpha and IL-18Rbeta on rat primary renal tubular
      epithelial cells].
AB  - AIM: To detect the expressions of the IL-18Ralpha mRNA and IL-18Rbeta mRNA in
      primary rat renal tubular epithelial cells (RTECs). METHODS: The culture of
      primary RTECs was performed by renal tubular segment sticking mass method. The
      cellular type was identified by immunocytochemical staining. The IL-18Ralpha mRNA
      and IL-18Rbeta mRNA expressions in RTECs were detected by RT-PCR. RESULTS: The
      result of immunocytochemical staining proved that the cultured cells were RTECs,
      IL-18Ralpha mRNA and IL-18Rbeta mRNA were detected in RTECs. CONCLUSION: IL
      18Ralpha mRNA and IL-18Rbeta mRNA are expressed in RTECs, which provide the
      experimental basis for exploring IL-18R role in renal interstitial fibrosis.

PMID- 15862144
TI  - [Synergistic role between rhIL-2 and adriamycin long circulating temperature
      sensitive liposome in targeting therapy on tumor].
AB  - AIM: To observe the synergistic role between rhIL-2 and adriamycin long
      circulating temperature-sensitive liposome (ALTSL) in targeting therapy of H22
      tumor-bearing mice and explore their anti-tumor mechanism. METHODS: The antitumor
      activity was evaluated by using the tumor's weight as an index. The prolongation
      rate of mouse life was calculated according to the survival time of the tumor
      bearing mice. The killer activity of NK cells and the lymphocyte transformation
      rate were detected by the LDH and MTT colorimetry, respectively. The apoptosis of
      tumor cells and the expression of p53, Fas, Fas-L and Caspase-3 were analyzed by
      flow cytometry (FCM). The expression of IL-2 mRNA and IL-12 mRNA in splenocytes
      was determined by RT-PCR. The pathologic changes of tumor, heart, liver and
      kidney tissues of the tumor-bearing mice were observed under light microscope.
      RESULTS: The tumoristatic rate of rhIL-2+ALTSL (73.5%) was higher than that of
      adriamycin liposome (ADML) group (67.0%). The survival time of tumor-bearing mice
      in ALTSL and rhIL-2+ALTSL groups was significantly extended as compared with the
      NS group (treated with normal saline) and the free ADM group (P <0.01 or P
      <0.05). The killer activities of NK cells of ALTSL group and rhIL-2+ALTSL group
      were higher than those of the NS and free ADM groups, and was highest in rhIL
      2+ALTSL group. The lymphocyte transformation rate of ALTSL+rhIL-2 group markedly
      increased ( P <0.01) as compared with the free ADM group. The result of RT-PCR
      indicated that the expression of IL-2 mRNA and IL-12 mRNA in splenocytes in the
      adriamycin long circulating liposome (ALCL) group was significantly higher than
      that in the free ADM group. The enhancement of rhIL-2+ALTSL on expression of IL-2
      mRNA and IL-12 mRNA was much stronger than that of ALTSL alone. The pathological
      examination indicated that in rhIL-2+ALTSL group, the tumor cells were mostly
      destroyed, and a large amount of lymphocytes and monocytes were found in tumor
      tissue. CONCLUSION: ALTSL can increase the anti-tumor effect and decreased the
      side-effects (such as the cytotoxicity) of ADM. rhIL-2+ALTSL can induce the
      apoptosis of tumor cells and enhance killer activities of T cells and NK cells.
      rhIL-2 and ALTSL can synergistically play the antitumor effect.

PMID- 15862145
TI  - [Study of mechanism of differentiation of bone stromal stem cells into neurons in
      vitro].
AB  - AIM: To explore the mechanism of differentiation of bone marrow stromal cells
      (BMSCs) into neurons in different micro-environments in vitro. METHODS: BMSCs
      were isolated from bone marrow of SD rats and cultured and expanded in vitro.
      After being identified by immunofluorescence staining, the BMSCs labeled with
      PKH67 were co-cultured with foetal brain neural cells in the same plate well or
      in two-layer Petri dish. 8 days later, the BMSCs were detected by
      immunofluorescence staining. RESULTS: After being co-cultured with foetal brain
      neural cells at the same time, some BMSCs differentiated into neurons. (32.72+/
      2.56)% of the BMSCs expressed neuron-specific enolase (NSE) in the co-cultured
      group, which was obviously much more than that in control group (P <0.05). Only
      (4.87+/-0.79)% of the BMSCs expressed NSE when the BMSCs co-cultured with foetal
      brain neural cells in two-layer Petri dish, which had no difference with the
      control group (P>0.05). The number of differentiated BMSCs was less than that of
      the co-cultured group (P <0.05). CONCLUSION: In vitro, the local microenvironment
      formed by neural cells can promote BMSCs to differentiate into neurons, and close
      contact between BMSCs and neural cells is an important condition that induce BMSC
      to differentiate into neurons.

PMID- 15862146
TI  - [Preparation of anti-Red antisera and its subcellular localization].
AB  - AIM: To prepare rabbit anti-Red antisera. METHODS: The bet, exo and gam genes of
      lambda phage were amplified by PCR from genomic DNA and cloned into the
      expression vector pDH2, respectively. Red proteins were induced to express at 42
      degrees C. The expressed proteins were analyzed by PAGE and thin-layer scanning.
      The antisera were prepared by immunizing rabbits with the three Red proteins,
      respectively. The titers and specificities of the antisera were detected by
      Western blot. RESULTS: Beta, Exo and Gam proteins accounted for about 40.3%,
      49.2% and 73.4% of total bacterial protein, respectively. The titers of the
      antisera were about 1:2,000. Western blot analysis indicated that the three
      antisera all had good specificities to the corresponding proteins. CONCLUSION:
      Specific anti-Red antisera are prepared successfully.

PMID- 15862147
TI  - [Cloning and expression of a novel gene restin and preparation of antisera
      against the recombinant restin].
AB  - AIM: To clone a new human gene, restin, from retinoic acid-treated promyelocytic
      cell line HL-60, express the protein in E.coli and prepare the antisera against
      the protein. METHODS: The restin gene was amplified from retinoic acid-treated
      promyelocytic cell line HL-60 by RT-PCR and cloned into a prokaryotic expression
      vector. The recombinant restin was induced to express in E. coli by temperature.
      After preliminary purification by SDS-PAGE, the restin protein was used to
      immunize rabbits to obtain antisera. The titers and specificity of the rabbit
      anti-restin antisera were tested by Western blot and immunofluorescence analysis.
      RESULTS: Recombinant restin with M(r) being about 26,000 was highly expressed in
      E. coli. The titers of the anti-sera to restin ranged from 1:100 to 1:800.
      Immunofluorescence analysis showed that restin distributed mainly in the nuclei
      of COS-7 cells. CONCLUSION: We successfully prepared the antisera against restin,
      which are useful for further investigation of biological functions of restin.

PMID- 15862148
TI  - [Expression of human-mouse chimeric antibody directed against Chikungunya virus
      with site-specific integration system].
AB  - AIM: To obtain CHO/dhfr(-) cells line with integrated FRT sequence in the
      chromosome transcription active site and to express human-mouse chimeric antibody
      directed against Chikungunya Virus by using the cell line. METHODS: The fusion
      gene of FRT and HBsAg was constructed by PCR and cloned into the MCS of pCI-neo
      to construct pCI-FRT-HBsAg. The pCI-FRT-HBsAg was transfected into CHO/dhfr(-)
      cells and cell clones with high expression of HBsAg were screened by detecting
      the amount of HBsAg with ELISA. A CHO cell clone with the highest expression was
      chosen and named as CHO/dhfr(-) FRT(+). pAFRT HFLF, a expression plasmid of
      chimeric antibody with RFT sequence was transfected into CHO/dhfr(-) FRT(+) cells
      and cell clones with high expression of the chimeric antibody were screened by
      increasing concentration of MTX. A CHO cell clone with high expression of the
      chimeric antibody was cultured in large scale and supernatant was collected from
      which the chimeric antibody was purified. The purified chimeric antibody was
      analyzed by SDS-PAGE, Western blot and IFA. RESULTS: A CHO/dhfr(-) cells line
      with integrated FRT sequence in the chromosome transcription active site was
      obtained successfully. A cell clone with yield of 5 mg/L of chimeric antibody was
      obtained, as compared with routine CHO cell expression system with a yield of 2
      mg/L. CONCLUSION: A cell line with integrated FRT sequence in the chromosome
      transcription active site was obtained and with it human-mouse chimeric antibody
      directed against Chikungunya virus was expressed. This system lays a solid
      foundation which can be used for expressing antibodies and other proteins.

PMID- 15862149
TI  - [Preparation of monoclonal antibody against human c-erbB2 and identification of
      its specificity].
AB  - AIM: To prepare monoclonal antibody(mAb) against human c-erbB2 and identify its
      specificity. METHODS: The epitope of human c-erbB2 antigen was analyzed by using
      computer software and a immunodominant epitope at the carboxyl-terminal was
      selected. A peptide consisting of 13 amino acids was synthesized and coupled with
      keyholelimpet hemocyanin (KLH), and then it was used to immunize BLAB/c mice. The
      splenocytes of the immunized mice were fused with Sp2/0 cells routinely and the
      hybridoma cells were selected by HAT selected culture, indirect ELISA, and
      immunohistochemical staining, and cloned by limiting dilution. The specificity of
      the mAb was identified by cross-reaction test and blocking test. RESULTS: A
      hybridoma cell line SC8C1, stably secreting anti-c-erbB2 mAb was obtained. The
      mAb SC8C1 could react to breast cancer tissue expressing c-erbB2 molecule but did
      not react to other c-erbB2-negative cells. The mAb will lose the activity after
      being blocked with synthesized 13 peptide. CONCLUSION: A anti-c-erbB2 mAb SC8C1
      is prepared successfully using synthesized 13 peptide as immunogen.

PMID- 15862150
TI  - [Preparation and characterization of monoclonal antibodies against human RANTES
      molecule].
AB  - AIM: To prepare monoclonal antibodies against human RANTES molecule and identify
      the expression of RANTES in rat small intestine after small bowel
      transplantation. METHODS: Murine mAbs were prepared by B lymphocyte hybridoma
      technique. The expression of RANTES in rat small intestine after small bowel
      transplantation was detected by immunohistochemistry. RESULTS: Four hybridoma
      cell lines secreting monoclonal antibodies to human RANTES, FMU-RANTES 1, FMU
      RANTES 2, FMU-RANTES 3 and FMU-RANTES 4, were established. The titers of a scetic
      mAbs reached to 1 x 10(-6) and the Ig subclass of FMU-RANTES 1, FMU-RANTES 3 and
      FMU-RANTES 4 was IgG1(kappa) and that of FMU-RANTES 2 was IgG2b(kappa). Among
      these mAbs, FMU-RANTES 1, FMU-RANTES 2 and FMU-RANTES 3 could bind human RANTES
      protein in Western bolt. FMU-RANTES 1, FMU-RANTES 2 and FMU-RANTES 4 could be
      used in immunohistochemistry staining. Rat RANTES molecule could be detected in
      the cyto plasm of epithelial cells in rat small intestine after small bowel
      transplantation. CONCLUSION: Four mAbs against RANTES molecule were prepared,
      which can provide a useful tool in research on the structure and function of
      RANTES molecule. High expression of RANTES may be involved in the rejection of
      allogeneic graft.

PMID- 15862151
TI  - [Preparation, characterization and preliminary application of monoclonal antibody
      against human mu chain].
AB  - AIM: To prepare monoclonal antibody (mAb) against human mu chain with high titer
      and establish a capture ELISA for early serological diagnosis of infectious
      diseases. METHODS: BALB/c mice were immunized with human IgM. Hybridoma cell line
      which could stably secret the mAb to human IgM was established by routine cell
      fusion technique. mAb's characteristics (titer, Ig subclass, specificity and
      relative affinity) were identified by indirect ELISA and Western blot,
      respectively. A capture ELISA was established by using purified mAb to capture
      specific IgM for early diagnosis of Japanese encephalitis. RESULTS: One hybridoma
      cell line 2E5 stably secreting mAb against human IgMmu chain was obtained. The
      titer of ascites of the mAb was 1 x 10(-6) and the Ig subclass was IgG1(kappa).
      Relative affinity of 2E5 was 1 x 10 (-5). Western blot analysis showed that mAb
      2E5 reacted specifically to mu chain. Both sensitivity and specificity of the
      capture ELISA in detecting specific IgM in Japanese encephalitis patients sera
      were high. CONCLUSION: mAb 2E5 against human mu chain was prepared successfully,
      and a capture ELISA for early serological diagnosis of Japanese encephalitis was
      set up.

PMID- 15862152
TI  - [The epitope analysis of beta Netrin and preparation and characterization of its
      antibodies].
AB  - AIM: To prepare and characterize anti-human beta-Netrin antibodies. METHODS: B
      cell dominant epitopes of human beta-Netrin C-terminal 114 amino acid sequences
      were predicated by the GoldKey software. One of the epitopes was synthesized and
      coupled with bovine serum album (BSA) by 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide hydrochloride (EDC). The BALB/c mice were immunized with the coupled
      protein. The splenocytes of immunized mice were fused with Sp2/0 cells by routine
      method and the hybridomas were selected in HAT medium. The hybridoma cells
      secreting specific antibody were detected by ELISA and cloned by limiting
      dilution. The titer specificity, and Ig subclass of anti-beta-Netrin mAbs were
      characterized by ELISA, Western blot and immunocytochemical staining. In
      addition, New Zealand rabbits were immunized with the coupled protein to prepare
      polyclonal antibody against beta-Netrin. The specificity of the antiserum was
      verified by Western blot. RESULTS: A 16-mer peptide NH2-FRGKRTLYPES-WTDRG-COOH
      was the dominant epitope of the B cells. Synthesized peptide coupled with BSA was
      used as the immunogen to immunize BALB/c mice. Three hybridoma cell lines that
      stably secrete specific mAbs were obtained. The result of immunocytochemical
      staining showed that prepared mAb specifically recognize the antigen in the
      neuronal cells. The polyclonal antibody against beta-Netrin had high specificity.
      Western blot analysis showed that the antiserum bind with the prokaryotically
      expressed beta-Netrin specifically. CONCLUSION: Using the synthesized peptides as
      hapten, we have prepared epitope-specific mAbs and pAb against beta-Netrin
      successfully.

PMID- 15862153
TI  - [Expression and antibody preparation of a novel serine protease ESP30].
AB  - AIM: To express ESP30, a novel serine protease, in Escherichia coli and to
      prepare anti-ESP30 antibody. METHODS: ESP30 gene was amplified by PCR from the
      genome of aeromonas hydrophila, and cloned into the expression vector pDH2. The
      ESP30 expression was carried out under thermal induction. The antiserum was
      prepared by immunizing rabbit with ESP30. The titer and specificity of the
      antibody were detected by ELISA and Western blot respectively. RESULTS: The ESP30
      non-fusion protein with relative molecular mass (M(r)) of 66,000 was highly
      expressed in E. coli. The rabbit antibody against ESP30 was obtained. The ELISA
      titer of antiserum against ESP30 was about 1:128,000. Western blot analysis
      showed that the antiserum could bind to the expressed ESP30 specifically.
      CONCLUSION: The rabbit antibody against ESP30 has been successfully prepared,
      which lays the foundation for further studying the structure and function of the
      novel protease ESP30.

PMID- 15862154
TI  - [One-step purification of monoclonal antibody against gp130 by cation exchange
      liquid chromatography].
AB  - AIM: To develop a one-step purification method of anti-gp130 monoclonal antibody
      (mAb) B-S12 from mouse ascites. METHODS: After filtrated by centrifugation, the
      ascites sample was loaded on a cation exchange column and purified by using ion
      strength gradient elution buffer. The effects of pH of the loading buffer and ion
      strength gradients of the elution buffer on the purity of antibody obtained were
      investigated. The antibody's biological activity was tested by MTT colorimetry.
      RESULTS: It was shown that the mAb B-S12 with a purity of over 90% could be
      achieved by using 20 mmol/L HEPES buffer (pH 4.0) as loading buffer and 0-1.0
      mol/L NaCl as elution buffer. The total recovery rate of the mAb was 52%. The
      purified antibody could stimulate the proliferation of XG-2 cell line.
      CONCLUSION: The established one-step purification method was simple and suitable
      for purification of mAb B-S12.

PMID- 15862155
TI  - [Secretory expression of chimeric Fab antibody HAb18 against human hepatocellular
      carcinoma in Pichia pastoris].
AB  - AIM: To express secretively chimeric Fab antibody HAb18 (cFab) against human
      hepatocellular carcinoma in Pichia pastoris. METHODS: Genes encoding CL chain and
      Fd fragment of cFab antibody HAb18 were subcloned into vectors pPIC9K and
      pPICZalphaA, respectively. After confirmed by DNA sequence analysis, the
      recombinant plasmids pPIC9K/CL and pPICZalphaA/Fd were transformed into the
      genome of Pichia pastoris GS115. Mut(+) multiple insert transformants were
      screened by G418 and Zeocin and then induced with 5 mL/L methanol to express
      cFab. RESULTS: 4 days after methanol induction, 26 mg/L of the cFab fragment was
      detected in the culture supernatant. Western blot proved that the expressed
      protein could specifically bind with HAb18GEF antigen. CONCLUSION: The successful
      expression of cFab/HAb18 in Pichia pastoris lays the foundation for large-scale
      production and further application of the antibody.

PMID- 15862156
TI  - [Expression of MMP-2 and MMP-9 in the tartrate-resistant acid phosphatase (TRAP)
      positive mononuclear and multinucleated cells is correlated with articular
      cartilage damage].
AB  - AIM: To examine the role of matrix metalloproteinases(MMP) expressed by the
      tartrate-resistant acid phosphatase (TRAP)-positive mononuclear and
      multinucleated cells in articular cartilage damage. METHODS: C57BL/6 mice were
      immunized by injection of chicken type II(CII) collagen to construct the collagen
      induced rheumatoid arthritis(CIA) model. The presence of TRAP positive cells in
      the synovial tissue of CIA mice was examined by enzyme histochemistry and
      expression of MMP-2,9 was assessed in TRAP positive cells by
      immunohistochemistry. RESULTS: Expression of MMP-2 (gelatinase A) and MMP-9
      (gelatinase B) was detected in TRAP positive mononuclear and multinucleated cell.
      Quantity of TRAP positive cells and the destruction of articular cartilage had a
      positive correlation (r(s) =0.903, P<0.01). Expression of MMP-2 and MMP-9 in TRAP
      positive cells was also correlated significantly with the destruction of
      articular cartilage (r(s) =0.954, P<0.01). CONCLUSION: This study suggests that
      MMP-2 and MMP-9 expression by TRAP positive mononuclear and multinucleated cells
      are involved in articular cartilage destruction in CIA.

PMID- 15862157
TI  - [Exploration of serum endothelin-1 as a marker of early radiation lung injury].
AB  - AIM: To explore the possibility of endothelin-1(ET-1) as a serological marker of
      early diagnosis and progression of radiation induced lung injury. METHODS: One
      hundred and ninety female rats were randomly divided into control group (group C)
      and experimental groups, namely, radiation group (group R), fluvastatin treatment
      group (group Flu), retinoic acid treatment group (group Ra) and dexemethasone
      treatment group (group Dex). The chests of rats in experimental groups were
      exposed to radiation by linear accelerator after anesthesia. The radiation dose
      for each rat was 15Gy, 2Gy per minute, and radiation distance was 1 meter. The
      next day after radiation, fluvastatin (20 mg. kg(-1). d(-1) ) was administered
      orally in group Flu, retinoic acid (20 mg. kg(-1). d(-1)) in group Ra and
      dexemethasone (3.33 mg. kg(-1). d(-1)) in group Dex. The rats in group C and
      group R were medicated with the equal volume of normal saline. On the 5th, 15th,
      30th, and 60th day after radiation, five rats were randomly chosen from each
      group respectively. The sera were harvested by decapitation or cardiopuncture and
      at the same time, lung tissues were cut off. The levels of serum ET-1 and LN were
      detected by radioimmunological assay(RIA). The pathologic changes of lung tissue
      were observed under light microscope. RESULTS: Compared to the control group,
      serum ET-1 level began to increase on the 5th day after exposure to radiation and
      reached the peak on the 60th day in group R. The levels of laminin and hyaluronic
      acid began to rise on the 30th day and the 60th day respectively. The elevation
      of serum ET-1 level in group R was obviously earlier than that in other groups
      and correlated to extent of lung injury. CONCLUSION: The serum ET-1 can be used
      as a marker of early diagnosis and dynamic changes of radiation lung injury.

PMID- 15862158
TI  - [Effect of phosphodiesterase inhibitor on expression of IL-8 mRNA in peripheral
      blood mononuclear cells from COPD patients].
AB  - AIM: To explore the inhibitory mechanism of phosphodiesterase(PDE) inhibitor on
      expression of IL-8 mRNA in peripheral blood mononuclear cells (PBMCs) from
      chronic obstructive pulmonary disease(COPD) patients. METHODS: PBMCs isolated
      from 20 COPD patients and 15 healthy subjects were co-cultured with non-selective
      inhibitor theophylline or PDE type IV inhibitor Rolipram. The expression of IL-8
      mRNA was assayed by RT-PCR. The expression of NF-kappaB was determined by
      immunocytochemical staining. The content of I-kappaB protein was detected by
      Western blot. RESULTS: The expression of IL-8 mRNA was elevated and the
      percentage of NF-kappaB nucleus positive cells was higher in COPD patients than
      in normal controls(P<0.01), while the expression of I-kappaB was lower in COPD
      patients (P<0.01). Theophylline of 1 mmol/L caused a decrease in the percentage
      of NF-kappaB nucleus positive cells (P<0.05). The expression of IL-8 mRNA and I
      kappaB were not affected by theophylline at the dose of 100 micromol/L or 1
      mmol/L. Rolipram inhibited the expression of IL-8 mRNA and the activation of NF
      kappaB(P<0.05). CONCLUSION: The results indicated that IL-8 mRNA may play a
      pathogenic role in the development of COPD and that selective PDE type IV
      inhibitor Rolipram inhibit the expression of IL-8 mRNA via NF-kappaB.

PMID- 15862159
TI  - [The differential expression of hypoxia-inducible factor-1alpha in placenta
      tissues from pregnancy induced hypertension and normal pregnancy].
AB  - AIM: To explore the differential expression of hypoxia-inducible factor-1alpha
      (HIF-1alpha) in placenta tissues from pregnancy induced hypertension and normal
      pregnancy. METHODS: The expression of HIF-1alpha protein and mRNA was detected by
      Western blot and real-time PCR, respectively. RESULTS: As compared with the
      expression levels of HIF-1alpha protein and mRNA in placenta tissues from normal
      pregnancy, those from pregnancy induced hypertension increased notably (P<0.05).
      CONCLUSION: The high expression of HIF-1alpha in the placenta tissues pregnancy
      induced may relate with pathogenesis and pathophysiological process of
      hypertension.

PMID- 15862160
TI  - [Kinetic changes of plasma IL-1 and IL-6 levels in MPTP-induced Parkinson's
      disease model mice and their relationship with brain asymmetry].
AB  - AIM: To set up Parkinson's disease (PD) model mice by using 1-methyl-4-phenyl-1,
      2, 3, 6-tetrahydropyridine (MPTP), detect the levels of plasma IL-1 and IL-6, and
      to explore their relationship with brain asymmetry. METHODS: Male C57BL/6J mice
      were divided into right pawed mouse group and left pawed mouse group according to
      paw preference test which reflects brain asymmetry. Mice were injected
      intraperitoneally with 25 mg/kg MPTP each day for 5 consecutive days. The mice
      were executed and blood samples were taken at 1, 3 and 14 days after the last
      time injection. Control mice were only injected with normal saline. The levels of
      plasma IL-6 and IL-1 were detected by ELISA. RESULTS: Plasma IL-6 level in normal
      control mice was low, but elevated dramatically at 14 days after last time
      injection of MPTP in PD model mice. Furthermore, IL-6 level of right pawed mice
      was higher than that of left pawed mice. Plasma IL-1 levels also increased on day
      3 after last time injection of MPTP, and the level of left pawed mice was higher
      than that of right pawed mice. CONCLUSION: IL-6 and IL-1 probably participate in
      the occurrence and progress of MPTP-induced PD in model mice, and were related
      with brain asymmetry.

PMID- 15862161
TI  - [Detection of antibody against Helicobacter pylori UreB by fluorescence polarized
      immunoassay using single epitope synthetic peptide as antigen].
AB  - AIM: To develop a new method for antibody detection based on fluorescence
      polarization (FP) technique. METHODS: BALB/c mice were immunized with single
      epitope synthetic 8 branches peptide antigen (SVEVGKVADL)8 of Helicobacter pylori
      (Hp) UreB protein. FP values of the corresponding linear peptide antigen labeled
      with FITC in different concentration were measured to determine the optimal
      concentration of the antigen. The antigenicity of the synthetic linear peptide
      was identified by FP assay. Then, the antibody-positive and negative murine sera
      were used in FP assay to determine the optimal dilution factor of serum samples.
      To apply FP technique in Hp antibody detection, 126 human serum samples were
      detected either by FPIA (fluorescence polarized immunoassay) using the single
      epitope linear synthetic peptide as antigen or by a commercial ELISA kit. Then,
      receiver operating characteristic (ROC) curve analysis was performed on the FPIA
      results by MedCalc software. RESULTS: The UreB single epitope peptide had strong
      antigenicity. 1.0 nmol/L of the synthetic linear peptide labeled with FITC was
      the optimal concentration of the antigen and the optimal dilution factor of serum
      sample was 1:25. In 77 Hp antibody-positive serum samples detected by ELISA, 66
      samples were positive by FP detection method. The sensitivity and specificity of
      the FPIA assay was 85.7% and 98%, respectively. CONCLUSION: The single epitope
      synthetic peptide antigen can be used in FP method for rapid detection of serum
      antibody against Hp UreB. The established FP assay for antibody detection may be
      used in clinical diagnosis in the future.

PMID- 15862162
TI  - [Preparation of polyclonal antiserum against beta subunit of rabbit BK channel].
AB  - AIM: To prepare polyclonal antiserum against beta subunit of rabbit BK channel in
      mice. METHODS: Gene encoding the intracellular fragment of rabbit BK channel's
      beta subunit was amplified by RT-PCR. The GST-beta fusion protein was expressed
      in E. coli. The fusion protein from PAGE gel was used to immunize BALB/c mice and
      prepare polyclonal antiserum. The specificity of antiserum was identified by
      ELISA and Western blot. RESULTS: A unique band about 300 bp was amplified by RT
      PCR and was verified to be BK channel beta subunit by DNA sequencing. The SDS
      PAGE analysis showed that the M(r) of the fusion protein was about 37,000. The
      purity of GST-beta fusion protein was over 95%. The polyclonal antiserum against
      GST-beta fusion protein could recognize both GST-beta fusion protein and beta
      protein in rabbit tissues. The highest titer of the antiserum was about
      1:128,000, as shown by Western blot and ELISA, respectively. CONCLUSION: The gene
      encoding the intracellular fragment of rabbit BK channel's beta subunit has been
      cloned. The polyclonal antiserum against beta subunit of rabbit BK channel with
      high titer and specificity has been prepared successfully.

PMID- 15862163
TI  - [Development of a method for isolation, culture and proliferation of mouse NK
      cells].
AB  - AIM: To establish a method to isolate, purify, and culture mouse nature killer
      (NK)-cells in vitro. METHODS: NK-cells were isolated from splenic mononuclear
      cells (MNC) by a two-step adherence system and magnetic microbeads actived cell
      sorting (MACS), then these cells were cultivated with feeder cells and IL-2 in
      RPMI 1640 medium for 5, 10, 15, and 20 days. The enriched cells were counted and
      stained with anti-mouse CD3-FITC and anti-mouse NK1.1-PE. The purity of the NK
      cells was determined by flow cytometry and the cytotoxicity to YAC-1 targets was
      detected by MTT assay. RESULTS: In the two-step adherence system, the enriched
      cells cultivated for 5, 10, 15, and 20 days were 0.5 x 10(7), 1.4 x 10(7), 2.6 x
      10(7), and 3.0 x 10(7) respectively, and the percent of CD3(-) NK1.1(+) cells was
      18.36%, 43.44%, 55.68%, and 60.03% respectively. The cytotoxicity to YAC-1
      targets was significantly higher than that of splenic MNC(P<0.01), and increased
      from 41.93% up to 54.38%, 66.54%, 79.38%, and 83.86% respectively at 25:1 of
      effector:target ratio. After NK-cells were purified by MACS, the purity reached
      93.60%ls, the enriched cells was 1.5 x 10(6), but proliferated to only 1.9 x
      10(6) 20 days later. CONCLUSION: NK-cells isolated by using the two step
      adherence system proliferate abundantly, and the purity reaches 55%-60%. The
      cytotoxicity to YAC-1 targets is about 80% at 25:1 of effector:target ratio.

PMID- 15862164
TI  - [The effect of short hairpin RNA on hTERT expression].
AB  - AIM: To study the effect of short hairpin RNA (shRNA) on hTERT expression.
      METHODS: Oligonucleotides encoding shRNA against hTERT was cloned into a
      mammalian shRNA expression vector pUC18U6 to form pUC18U6ht which was transfected
      into HepG2 cells by using liposome. HepG2 cells transfected by pUC18U6 and
      pUC18U6GFPsir which expressed shRNA against green fluorescent protein were used
      as controls. hTERT mRNA in the transfected cells was quantified by using real
      time fluorescent RT-PCR. RESULTS: Compared with the controls, the short hairpin
      RNA against hTERT decreased the hTERT mRNA level by 49% (P<0.05). CONCLUSION:
      hTERT expression was reduced by the shRNA.

PMID- 15862165
TI  - [Construction of an expression vector under the control of hTERT promoter].
AB  - AIM: To construct a luciferase expression vector driven by hTERT(human telomerase
      reverse transcriptase) core promoter and identify the transcriptional activity of
      the vector in tumor cells and normal cells. METHODS: hTERT gene core promoter was
      amplified by PCR using the total genomic DNA from HeLa cells as template. The
      amplified gene fragment was subsequently cloned into PGL3-basic vector. Then the
      expression vector was confirmed by restriction enzyme digestion and PCR analysis.
      The luciferase activity driven by the hTERT gene core promoter was identified
      after transient transfection of the expression vector into tumor cells and normal
      cells. RESULTS: The luciferase activity was high in the transfected tumor cells,
      and very low in transfected normal cells. CONCLUSION: hTERT gene core promoter is
      tumor-specific and may be useful in gene therapy of tumor.

PMID- 15862166
TI  - RPE lipofuscin and its role in retinal pathobiology.
AB  - Emerging evidence indicates that the autofluorescent pigments that accumulate as
      lipofuscin in retinal pigment epithelial (RPE) cells may reach levels that
      contribute to a decline in cell function. Since recent findings with respect to
      the origin, composition and adverse effects of RPE lipofuscin have informed our
      view of this material, the goal of this article is to review our current
      understanding of these issues.

PMID- 15862167
TI  - The role of viral and host genes in corneal infection with herpes simplex virus
      type 1.
AB  - Herpes simplex virus infection of the eye is the leading cause of blindness due
      to infection in the US despite the availability of several antiviral drugs.
      Studies with animal models have shown that three factors, innate host resistance,
      the host adaptive immune response, and the strain of virus interact to determine
      whether an infection is asymptomatic or proceeds to the development of blinding
      keratitis (HSK). Of these, the role of adaptive immunity has received the most
      attention. This work has clearly shown that stromal keratitis is an
      immunopathological disease, most likely due to the induction of a delayed type
      hypersensitivity response. Substantially less is known about the role of specific
      host genes in resistance to HSK. The fact that different strains of virus display
      different disease phenotypes indicates that viral 'virulence' genes are critical.
      Of the 80 plus HSV genes, few have been formally tested for their role in HSV
      keratitis. Most studies of virulence genes to date have focused on a single gene
      or protein and large changes in disease phenotypes are usually measured. Large
      changes in the ability to cause disease are likely to reduce the fitness of the
      virus, thus such studies, although useful, do not mimic the natural situation.
      Viral gene products are known to interact with each other, and with host proteins
      and these interactions are critical in determining the outcome of infection. In
      reality, the 'constellation' of genes encoded by each particular strain is
      critical, and how this constellation of genes works together and with host
      proteins determines the outcome of an infection. The goal of this review is to
      discuss the current state of knowledge regarding the role of host and viral genes
      in HSV keratitis. The roles of specific genes that have been shown to influence
      keratitis are discussed. Recent data showing that different viral genes cooperate
      to influence disease severity and confirming that the constellation of genes
      within a particular strain determines the disease phenotype are also discussed,
      as are the methods used to test the role of viral genes in virulence. It will
      become apparent that there is a paucity of information regarding the function of
      many viral genes in keratitis. Improving our knowledge of the role of viral genes
      is critical for devising more effective treatments for this disease.

PMID- 15862168
TI  - Rhodopsin-like immunoreactivity in the 'all cone' retina of the chameleon
      (Chameleo chameleo).
AB  - Chameleons (Order, Reptilia: Family, Lacertilia) are unique among vertebrates in
      being able to make independent eye movements. The organisation of their retina,
      however, closely ressembles that of other diurnal lizards; based on morphological
      studies, it is typically described as containing only cone photoreceptors. We
      show here that a subpopulation of the photoreceptors are immunolabelled by an
      antibody directed against rhodopsin, suggesting the presence of rods. We conclude
      that in the nonmammalian retina, rods and cones cannot be exclusively
      distinguished on purely morphological grounds.

PMID- 15862169
TI  - Effect of CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure
      in glaucomatous monkey eyes.
AB  - To evaluate the effect of CS-088, an angiotensin AT1 receptor antagonist, on
      intraocular pressure (IOP) in monkey eyes with unilateral laser-induced glaucoma.
      A multiple-dose study was performed in 8 glaucomatous monkey eyes. One 50 microl
      drop of CS-088, 2% or 4%, was topically applied to the glaucomatous eye at 9:30
      a.m. and 3:30 p.m. for 5 consecutive days. IOP was measured hourly for 6 hours
      beginning at 9:30 a.m. for one baseline day, one vehicle-treated day, and daily
      for 5 days of treatment with CS-088. The washout period between the two drug
      concentrations was at least 2 weeks. Twice daily administration of 2 % CS-088 for
      5 days did not reduce the IOP until the third dose on day 2 of the treatment
      regimen. A significant (p<0.02) reduction in IOP began 1 hour after the third
      dose, and lasted for 3 hours. The maximum reduction in IOP was 5.3+/- 0.8 (mean+/
      SEM) mmHg (15%) (p<0.001), with the longest duration of IOP reduction of at least
      6 hours after dosing on day 5. The 4% dose of CS-088 reduced (p<0.05) IOP from 1
      to 5 hours after the first dose. The maximum reduction in IOP was 6.9+/-1.0 mmHg
      (20%), with the longest duration of IOP reduction of at least 18 hours after
      administration on day 5. Both 2% and 4% CS-088 showed enhancement of the ocular
      hypotensive effect with repeated dosing. 4% CS-088 produced greater (p<0.05) IOP
      reduction with longer duration of action than 2%. Topically applied CS-088, a new
      antagonist drug at the angiotensin AT1 receptor, reduced IOP in glaucomatous
      monkey eyes in a dose-dependent manner.

PMID- 15862170
TI  - Nerve growth factor and corneal wound healing in dogs.
AB  - Nerve growth factor in the tear film and corneal epithelium is hypothesized to
      play an important role in ocular surface maintenance and corneal wound healing.
      The purpose of this study was to determine the expression of nerve growth factor
      and its high affinity (trkA) receptor in tears, cornea, and lacrimal glands of
      normal dogs, the modulation of nerve growth factor and its trkA receptor during
      corneal wound healing, and the effect of topical nerve growth factor application
      on canine corneal epithelial wound healing. In the first of three experiments,
      the nerve growth factor content of tears, corneal epithelium, lacrimal gland, and
      3rd eyelid gland was determined in normal dogs by enzyme-linked immunosorbent
      assay and the expression of nerve growth factor and its trkA receptor were
      evaluated in the cornea and lacrimal glands by immunohistochemistry. In a second
      experiment, unilateral corneal epithelial defects were created, and tissues were
      evaluated for changes in nerve growth factor or trkA expression for 1 week. In a
      third experiment, bilateral corneal epithelial defects were created and the right
      eyes in each animal were treated 4 times daily with either recombinant human
      nerve growth factor, murine nerve growth factor, or nerve growth factor-blocking
      antibody. The results of this study showed that nerve growth factor levels in
      normal dog tears, corneal epithelium, third eyelid gland and lacrimal gland were
      15.4+/-4.6 ng ml(-1), 33.5+/-12.3, 52.4+/-17.4 and 48.8+/-9.4 ng g(-1),
      respectively. NGF and trkA receptors were identified by immunohistochemistry in
      all tissues examined. After unilateral corneal wounding, nerve growth factor
      concentration increased in the tears bilaterally for 3 days, especially in the
      wounded eye, and then returned to pre-wounding values. Nerve growth factor
      content, and immunohistochemical staining for nerve growth factor and trkA,
      increased significantly in the ipsilateral cornea epithelium following unilateral
      wounding. Nerve growth factor concentrations in lacrimal and third eyelid glands
      also increased bilaterally (p<0.01) after unilateral wounding. Time to wound
      closure and rate of epithelial migration did not differ significantly between
      nerve growth factor-treated, nerve growth factor antibody-treated, and control
      eyes. In conclusion, nerve growth factor is present under resting physiologic
      conditions in normal canine tears, and nerve growth factor and its trkA receptor
      are present under resting conditions in normal canine corneal epithelium,
      lacrimal gland and third eyelid gland. Nerve growth factor is elevated in the
      tears, cornea, and lacrimal glands after corneal epithelial wounding; however,
      topical application of nerve growth factor, or its blocking antibody does not
      modulate corneal wound healing in the normal dog eye.

PMID- 15862171
TI  - Packages of vitreous collagen (type II) in the human retina: an indication of
      postnatal collagen turnover?
AB  - The purpose of this study was to evaluate the vitreoretinal border in the (pre
      )equatorial area in nonpathologic human donor eyes, because the majority of
      retinal defects induced by posterior vitreous detachment (PVD) are located there.
      Nine eyes (24-80 years) were fixed and embedded in Technovit 8100. After
      evaluation by light microscope, areas of interest were selected for
      immunotransmission electron microscope. Anti-type II collagen antibody was used
      to stain vitreous fibrils and lamellae; anti-type IV collagen antibody was used
      to identify the internal limiting lamina (ILL); anti-vimentin and anti-CD-68
      antibodies stained retinal Muller cells and macrophages, respectively.
      Observations included fusing of lamellae with the ILL, an intravitreal course of
      the ILL, and clear focal interruptions in the ILL. In addition, an obvious
      finding was the presence of intraretinal packages of type II collagen.
      Interestingly these collagen packages were closely related to Muller cells and,
      in several eyes, also to macrophages, cell debris and interruptions in the ILL.
      In our opinion, the collagen packages can reflect the net result of a process of
      interactive remodelling, in which both breakdown and synthesis of vitreous and
      ILL collagens take place. Connections between vitreous and intraretinal collagen
      networks can make the (pre-)equatorial area more vulnerable to tearing and
      retinal detachment in the case of liquefaction and PVD.

PMID- 15862172
TI  - Vascular endothelial growth factor expression and secretion by retinal pigment
      epithelial cells in high glucose and hypoxia is protein kinase C-dependent.
AB  - Retinal pigment epithelial (RPE) cells express vascular endothelial growth factor
      (VEGF) in response to high glucose or hypoxia. We hypothesised that VEGF
      expression and secretion by RPE cells in high glucose and hypoxia are regulated
      by protein kinase C (PKC). Primary cultured RPE cells from Sprague-Dawley rats
      were growth-arrested for 48 hr in 0.5% FBS in 5.6 or 30 mm D-glucose. Cells were
      exposed to hypoxic conditions (<1% O(2), 5% CO(2)) for the last 15-18 hr of
      growth-arrest. PKC -alpha, -beta(1), -delta, -epsilon, and -zeta were expressed
      by RPE cells and exposure to high glucose for 48 hr had no effect on expression
      as demonstrated by Western immunoblotting. High glucose, hypoxia or VEGF
      stimulated translocation of a number of the PKC isozymes to the membrane or
      particulate fractions implying activation. In response to high glucose or acute
      phorbol myristate acetate (PMA) stimulation, VEGF mRNA analysed by RT-PCR was
      increased. Intracellular VEGF protein identified by immunoblotting and confocal
      immunofluorescence imaging was significantly increased by high glucose, hypoxia
      or acute PMA stimulation. Calphostin C or a specific inhibitor of PKC-zeta
      prevented high glucose-stimulated VEGF expression in high glucose. VEGF
      secretion, as measured by ELISA in the culture medium, was enhanced in hypoxia
      but not in high glucose. Following exposure of RPE cells to PMA for 24 hr, PKC
      delta was significantly down regulated, whereas PKC-alpha, -beta, -epsilon and 
      zeta remained unchanged. Secretion of VEGF in normal or high glucose, or hypoxia
      was significantly reduced following treatment with PMA for 24 hr but not with the
      PKC-zeta inhibitor. We conclude that in high glucose and hypoxia PKC isozymes are
      activated and are necessary for VEGF expression. Secretion of VEGF is enhanced in
      hypoxia and appears to be regulated by PKC-delta. RPE cells may contribute to the
      pathogenesis of retinopathy caused by high glucose and hypoxia through the
      expression and secretion of VEGF that are regulated by PKC isozymes.

PMID- 15862173
TI  - The transcription factor c-jun is activated in retinal ganglion cells in
      experimental rat glaucoma.
AB  - This study investigates the role of the MAP kinase pathway including c-jun, ATF-2
      and JNK in glaucomatous eyes of rats and in optic nerve transection. Glaucoma was
      induced in one eye of 51 adult Wistar rats by laser treatment to the trabecular
      meshwork. Eighteen further rats underwent unilateral optic nerve transection. We
      studied the transcription factor c-jun, its activated form, phospho-c-jun, the
      transcription factor p-ATF-2, and the enzyme JNK by immunohistochemistry. The
      activation of p-c-jun was also investigated using western blot analysis. Treated
      and control eyes were compared in a masked way at multiple time points after
      injury. We found a statistically significant increase in immunolabelling for c
      jun and phospho-c-jun in retinal ganglion cells (RGCs) from 1 day to 4 weeks
      after intraocular pressure (IOP) elevation. At 1 and 2 days after the laser
      treatment, a mean of 2.9+/-3.3 RGCsmm(-1) were positive for c-jun (n=12, p=0.005,
      t-test), increasing to a mean of 13.4+/-7.5 cells mm(-1) at 1 week (n=18,
      p=0.00005), and decreasing to 2.3+/-2.0 cells mm(-1) at 2 weeks (n=5, p=0.04) and
      0.1+/-0.1 cells mm(-1) at 2 months. Few of the 47 control eyes had any labelling
      for c-jun or phospho-c-jun, while between 80 and 100% of elevated IOP eyes showed
      positivity during the first 2 weeks of experimental glaucoma. After optic nerve
      transection, c-jun and phospho-c-jun were also significantly activated at 1, 2
      and 9 days (p<0.03, t-test). Western blot analysis demonstrated significantly
      increased phospho-c-jun amounts in both transected and glaucomatous eyes compared
      to control fellow eyes 1 week following treatment. JNK was not significantly
      activated in glaucoma or optic nerve transection. P-ATF-2 was not significantly
      activated in glaucoma, but was significantly increased 2 days after optic nerve
      transection. We conclude that the process leading to RGC death in experimental
      glaucoma and after optic nerve transection involves the activation of c-jun at
      the RGC layer. C-jun is activated more gradually in glaucoma then after optic
      nerve transection.

PMID- 15862175
TI  - FK506 blocks activation of the intrinsic caspase cascade after optic nerve crush.
AB  - Retinal ganglion cells die by apoptosis after optic nerve crush. FK506 has been
      shown to be neuroprotective in this model but the mechanism(s) by which it exerts
      these actions remains unknown. We and others have shown that caspase 9 is cleaved
      in the retina in other injury models and we hypothesized that the neuroprotection
      observed with FK506 was mediated by interference with caspase 9 activation. The
      present study examined the cellular localization of caspase 9 cleavage after
      intraorbital optic nerve crush in rats, the time course of caspase 9 cleavage
      after optic nerve crush and the ability of orally administered FK506 to block
      caspase 9 cleavage after optic nerve crush. We show by immunohistochemistry that
      cleaved caspase 9 is present in retinal ganglion cells (identified by prior
      backlabelling) after optic nerve crush. Immunoblot analysis showed that caspase 9
      cleavage is significantly elevated 5 and 8 days after optic nerve crush. We show
      that orally administered FK506 reaches the retina and is pharmacologically active
      in retinal tissue. Furthermore, the oral administration of FK506 5 mg kg(-1) day(
      1) blocks the cleavage of caspase 9 at both time points. These data suggest that
      caspase 9 activation may play an important role in retinal ganglion cell death
      following optic nerve crush and that the neuroprotection seen with FK506 may be
      mediated by interfering with the activation of caspase 9.

PMID- 15862174
TI  - Topical application of culture supernatant from human amniotic epithelial cells
      suppresses inflammatory reactions in cornea.
AB  - Human amniotic epithelial cells (HAEC) may be a source of soluble anti
      inflammatory factors. The purpose of this study is to determine the effect of
      topically applied HAEC culture supernatant on corneal inflammatory reactions.
      HAEC were obtained from a placenta and cultured for 48 hr, and the supernatant
      was collected. The conditioned medium from HAEC contained small amounts of human
      interleukin-1 receptor antagonist (IL-1ra). Intrastromal sutures were placed in
      the cornea of BALB/c mice to induce corneal neovascularisation. Superficial
      cauterisation was applied to induce recruitment or activation of antigen
      presenting cells (APCs) in the cornea without neovascularisation. HAEC
      conditioned medium, placebo, or recombinant human IL-1ra was topically applied
      three times daily for 2 weeks. Suture-induced corneal neovascularisation was
      evaluated microscopically for 8 weeks. The cauterised corneas were harvested at 2
      weeks, and the MHC class II(+) APCs were quantified by immunofluorescent staining
      and confocal microscopy. Inflammatory cytokine gene expression in the cauterised
      corneas was analyzed by a multiprobe ribonuclease protection assay. Conditioned
      medium from HAEC led to a profound suppression of corneal neovascularisation and
      fewer MHC class II(+) APCs in the epithelium. In contrast, human IL-1ra was only
      slightly effective in suppressing corneal inflammatory reactions. mRNA expression
      of murine IL-1ra and IL-1beta in the cauterised corneas was markedly suppressed
      after application of the conditioned medium. These results suggest that HAEC are
      a source of soluble anti-inflammatory factors and that conditioned medium from
      HAEC contains factors other than IL-1ra that suppress corneal inflammation.

PMID- 15862176
TI  - Characterization of adenosine receptors in bovine corneal endothelium.
AB  - Previous studies indicated that adenosine can increase [cAMP](i) and stimulate
      fluid transport by corneal endothelium. The purpose of this study was to
      determine which adenosine receptor subtype(s) are expressed and to examine their
      functional roles in modulating [cAMP](i), [Ca(2+)](i) and effects on Cl(-)
      permeability in corneal endothelium. We screened bovine corneal endothelium (BCE)
      for adenosine receptor subtypes by RT-PCR and immunoblotting, and examined the
      effects of pharmacological agents on adenosine stimulated Cl(-) transport,
      [cAMP](i) and [Ca(2+)](i). RT-PCR indicated the presence of A(1) and A(2b)
      adenosine receptors, while A(2a) and A(3) were negative. Western blot (WB)
      confirmed the presence of A(2b) ( approximately 50 kDa) and A(1) ( approximately
      40 kDa) in fresh and cultured BCE. Ten micromolar adenosine increased [cAMP](i)
      by 2.7-fold over control and this was inhibited 66% by 10 microm alloxazine, a
      specific A(2b) blocker. A(1) activation with 1 micromN(6)-CPA (a specific A(1)
      agonist) or 100 nm adenosine decreased [cAMP](i) by 23 and 6%, respectively.
      Adenosine had no effect on [Ca(2+)](i) mobilization. Indirect immunofluorescence
      localized A(2b) receptors to the lateral membrane and A(1) to the apical surface
      in cultured BCE. Adenosine significantly increased apical Cl(-) permeability by
      2.2 times and this effect was nearly abolished by DMPX (10 microm), a general
      A(2) blocker. Adenosine-induced membrane depolarization was also inhibited by 33%
      (n=6) in the presence of alloxazine. Bovine corneal endothelium expresses
      functional A(1) and A(2b) adenosine receptors. A(1), preferentially activated at
      <1 microm adenosine, acts to decrease [cAMP](i) and A(2b), activated at >1 microm
      adenosine, increase [cAMP](i).

PMID- 15862177
TI  - Stimulation of cannabinoid (CB1) and prostanoid (EP2) receptors opens BKCa
      channels and relaxes ocular trabecular meshwork.
AB  - Prostanoids and cannabinoids have ocular hypotensive and neuroprotective
      properties. The effect of the prostanoid AH13205 (EP2), the thromboxane-mimetic
      U46619, the cannabinoid (CB) agonists WIN55212-2 and CP 55,940, endothelin-1 (ET
      1) and 8-bromo-cAMP on the membrane currents of trabecular meshwork (TM) cells
      were measured using the patch-clamp technique and compared to their effects on TM
      contractility. Previous studies show relaxation of TM to AH 13205 and other
      substances that elevate cAMP, while U46619 and endothelin-1 contract TM. This
      study shows that after contraction (100%) with carbachol (10(-6)m), the CB
      agonist CP 55,940 dose-dependently reduced contractility to 83+/-4% (n=9) (10(
      6)m) and 61+/-10%, (n=7) (10(-5)m). In the presence of both the CB1 antagonist
      AM251 (10(-6)m) and CP 55,940 (10(-5)m), the contractile response to carbachol
      reached 84+/-3% (n=6) of the original level. In patch-clamp experiments, membrane
      permeable 8-bromo-cAMP (10(-4)m) had no effect on currents of TM cells. In
      contrast, AH 13205 and two cannabinoids reversibly enhanced outward current
      through high-conductance Ca(2+)-activated K(+) channels (BKCa, BK, maxi-K) to the
      following values (in % of the initial value at 100 mV): AH 13205 (10(-5)m): 200+/
      28% (n=6), CP 55,940 (10(-6)m): 196+/-33% (n=7), CP 55,940 (10(-5)m): 484+/-113%
      (n=7), WIN55212-2 (10(-5)m): 205+/-41% (n=10). Iberiotoxin (10(-7)m) completely
      blocked these responses. The current response to CP 55,940 (10(-5)m) could be
      partially blocked by the CB1 antagonist AM251 (10(-6)m). Conversely, the
      contractile agents in this study either caused a transient reduction in outward
      current (ET-1(5x10(-8)m)) or had no effect (U46619 (10(-6)m)). We conclude that
      stimulation of EP2 and CB1 receptors in TM is coupled to the activation of BKCa
      channels via a non-diffusible second messenger cascade. This effect may
      contribute to the relaxant activity of EP2 and CB1 agonists in isolated TM
      strips, modulating ocular outflow.

PMID- 15862178
TI  - Age-related nuclear cataract-oxidation is the key.
AB  - Age is by far the biggest risk factor for cataract, and it is sometimes assumed
      that cataract is simply an amplification of this aging process. This appears not
      to be the case, since the lens changes associated with aging and cataract are
      distinct. Oxidation is the hallmark of age-related nuclear (ARN) cataract. Loss
      of protein sulfhydryl groups, and the oxidation of methionine residues, are
      progressive and increase as the cataract worsens until >90% of cysteine and half
      the methionine residues are oxidised in the most advanced form. By contrast,
      there may be no significant oxidation of proteins in the centre of the lens with
      advancing age, even past age 80. The key factor in preventing oxidation seems to
      be the concentration of nuclear glutathione (GSH). Provided that nuclear GSH
      levels can be maintained above 2 mm, it appears that significant protein
      oxidation and posttranslational modification by reactive small molecules, such as
      ascorbate or UV filter degradation products, is not observed. Adequate coupling
      of the metabolically-active cortex, the source of antioxidants such as GSH, to
      the quiescent nucleus, is crucial especially since it would appear that the
      cortex remains viable in old lenses, and even possibly in ARN cataract lenses.
      Therefore it is vital to understand the reason for the onset of the lens barrier.
      This barrier, which becomes apparent in middle age, acts to impede the flow of
      small molecules between the cortex and the nucleus. The barrier, rather than
      nuclear compaction (which is not observed in human lenses), may contribute to the
      lowered concentration of GSH in the lens nucleus after middle age. By extending
      the residence time within the lens centre, the barrier also facilitates the
      decomposition of intrinsically unstable metabolites and may exacerbate the
      formation of H(2)O(2) in the nucleus. This hypothesis, which is based on the
      generation of reactive oxygen species and reactive molecules within the nucleus
      itself, shifts the focus away from theories for cataract that postulated a
      primary role for oxidants generated outside of the lens. Unfortunately, due to
      marked variability in the lenses of different species, there appears at present
      to be no ideal animal model system for studying human ARN cataract.

PMID- 15862179
TI  - Identification of mouse retinal genes differentially regulated by dim and bright
      cyclic light rearing.
AB  - Bright cyclic light rearing protects BALB/c mice from light-induced photoreceptor
      apoptosis compared to dim cyclic light rearing. We used a microarray approach to
      search for putative neuroprotection genes that were up- or down-regulated under
      these environmental conditions. Retinal protection by bright cyclic rearing was
      determined by quantitative histology and DNA fragmentation analysis. Total RNA
      was isolated from 5-week-old mice raised in bright (400 lux) or dim (5 lux)
      cyclic light and prepared for analysis on microarrays produced using a 70-mer
      oligonucleotide library that represented 16,463 mouse genes. Genes of interest
      were identified using statistically robust bioinformatics analysis methods that
      were developed in-house. Changes in some genes were confirmed with quantitative
      real time PCR. We found that 952 genes were up- or down-regulated by bright
      cyclic light rearing compared to dim cyclic light rearing. One hundred and eighty
      four of them, having >/=2-fold differences, were grouped into 13 categories, and
      selected for further consideration. Eleven up-regulated and two down-regulated
      genes were confirmed by semi-quantitative PCR. Five neuroprotection-associated
      genes were up-regulated by bright cyclic light rearing as confirmed by real-time
      PCR. The human orthologue chromosomal location of 22 differentially expressed
      genes map to known retinal degeneration loci. Using PathwayAssist software, we
      modeled the pathway networks of up- and down-regulated genes that are
      functionally related to the retina. We identified retinal genes that are
      differentially regulated by environmental light history. Those that directly
      affect cell processes such as survival, apoptosis, and transcription are likely
      play a pivotal role in the regulation of retinal neuroprotection against light
      induced photoreceptor apoptosis.

PMID- 15862180
TI  - Cochlin deposits in the trabecular meshwork of the glaucomatous DBA/2J mouse.
AB  - Cochlin deposits were observed in the trabecular meshwork (TM) of 8-month-old
      glaucomatous DBA/2J mice, coincident with the reported onset of increased
      intraocular pressure and optic nerve damage. An age-dependent increase in cochlin
      was observed up to 10 months of age and was paralleled by a decrease in type II
      collagen. Similar expression patterns exist in the TM of humans with primary open
      angle glaucoma. Cochlin deposits, absent in non-glaucomatous mouse and human TM,
      may disrupt the TM extracellular matrix and obstruct aqueous humor circulation.
      Studies of DBA/2J mice offer promise for understanding the role cochlin may play
      in glaucoma.

PMID- 15862182
TI  - Hormonal influences on sexually differentiated behavior in nonhuman primates.
AB  - Sexually dimorphic behavior in nonhuman primates results from behavioral
      predispositions organized by prenatal androgens. The rhesus monkey has been the
      primary primate model for understanding the hormonal organization of sexually
      dimorphic behavior. Historically, female fetuses have received high prenatal
      androgen doses to investigate the masculinizing and defeminizing effects of
      androgens. Such treatments masculinized juvenile and adult copulatory behavior
      and defeminized female-typical sexual initiation to adult estrogen treatment.
      Testosterone and the nonaromatizable androgen, 5alpha-dihydrotestosterone,
      produced similar effects suggesting that estrogenic metabolites of androgens are
      not critical for masculinization and defeminization in rhesus monkeys. Long
      duration androgen treatments masculinized both behavior and genitalia suggesting
      that socializing responses to the females' male-like appearance may have produced
      the behavioral changes. Treatments limited to 35 days early or late in gestation
      differentially affected behavioral and genital masculinization demonstrating
      direct organizing actions of prenatal androgens. Recent studies exposed fetal
      females to smaller doses of androgens and interfered with endogenous androgens
      using the anti-androgen flutamide. Low dose androgen treatment only significantly
      masculinized infant vocalizations and produced no behavioral defeminization.
      Females receiving late gestation flutamide showed masculinized infant
      vocalizations and defeminized interest in infants. Both late androgen and
      flutamide treatment hypermasculinized some male juvenile behaviors. Early
      flutamide treatment blocked full male genital masculinization, but did not alter
      their juvenile or adult behavior. The role of neuroendocrine feedback mechanisms
      in the flutamide effects is discussed. Sexually differentiated behavior
      ultimately reflects both hormonally organized behavioral predispositions and the
      social experience that converts these predispositions into behavior.

PMID- 15862183
TI  - Social stress: from rodents to primates.
AB  - Social stress is associated with development of many psychological and
      physiological disturbances in humans. Animal models are needed to determine the
      etiology of these diseases and to develop rational clinical therapies to treat
      those afflicted. Rodent and non-human primate models of social stress have been
      developed to address these needs and contribute in complementary ways to the
      understanding of social stress. In this review, we provide an overview of common
      rodent and non-human primate models of social stress used in the laboratory with
      a focus on social hierarchy models. The implications of the current findings on
      understanding of the development of stress-related disease will also be
      discussed.

PMID- 15862184
TI  - Is mom too sensitive? Impact of maternal stress during gestation.
AB  - Studies have documented the detrimental impact of gestational and postpartum
      maternal stress on the developing offspring. In susceptible individuals, stress
      has been associated with everything from brain developmental delays to
      emotionality and behavior disorders. Understanding the genetics and developmental
      window of greatest stress sensitivity is vital to providing the best preventative
      care and therapeutic targets. Corticotropin-releasing factor (CRF) and its
      receptors (CRFR1 and CRFR2) are the key regulators of the endocrine stress
      response and are critical in maintenance of organismal homeostasis. Dysregulation
      of these stress pathways can result in an increased sensitivity to stress. Mice
      deficient for CRFR2 show such a dysregulation and have been found to be a
      valuable genetic model of increased stress sensitivity. Initial comparisons
      utilizing this mouse model in studies examining maternal behaviors and cross
      fostering outcome validate the complex nature-nurture contribution. Using this
      model, altered stress responsivity in offspring appears to require both a genetic
      predisposition to stress sensitivity and a postnatal environment that influences
      it.

PMID- 15862185
TI  - Down syndrome, Alzheimer's disease and seizures.
AB  - Neuropathologically, Alzheimer-type abnormalities are demonstrated in patients
      with Down syndrome (DS), both demented and nondemented and more than a half of
      patients with DS above 50 years develop Alzheimer's disease (AD). The
      apolipoprotein E epsilon4 allele, oestrogen deficiency, high levels of Abeta1-42
      peptide, elevated expression of BACE2, and valine polymorphism of prion protein
      gene are associated with earlier onset of dementia in DS individuals. Advanced AD
      alone may be an important risk factor for new-onset seizures in older adults and
      age above 60 years is a recognized risk factor for poor outcome from convulsive
      and nonconvulsive status epilepticus. DS patients aged over 45 years are
      significantly more likely to develop Alzheimer's disease than those less than 45
      years and up to 84% demented individuals with DS develop seizures. Late-onset
      epilepsy in DS is associated with AD, while early-onset epilepsy is associated
      with an absence of dementia. In AD patients with a younger age of dementia onset
      are particularly susceptible to seizures. DS adults with epilepsy score
      significantly higher overall on the adaptive behaviour profile. Language function
      declined significantly more rapidly in AD patients with seizures and there is a
      good correlation between the severity of EEG abnormalities and cognitive
      impairment whereas in DS slowing of the dominant occipital rhythm is related to
      AD and the frequency of the dominant occipital activity decreases at the onset of
      cognitive deterioration.

PMID- 15862186
TI  - Evaluating cognitive functions with visual and auditory number assays and P300 in
      children with epilepsy.
AB  - This study was planned to evaluate cognitive functions, especially attention and
      immediate recall, in children with epilepsy by using P300 and neuropsychological
      tests, which included visual and auditory number assays. Fifty five patients with
      partial seizures, 45 patients with generalized seizures and 20 patients with
      intractable seizures were enrolled in the study. Twenty five healthy children
      were taken as the control group. The results were as follows: 1. P300 latencies
      were significantly longer in the intractable and partial groups when compared
      with the control subjects. 2. The duration of epilepsy, seizure frequency,
      cerebral imaging pathologies were not significantly correlated with delayed P300
      latencies. 3. The results of the visual and auditory number assays test showed
      significant abnormalities when each of the three groups were compared with the
      normal controls. 4. Though some subgroups of the neuropsychological tests were
      correlated with the P300 latencies, an overall significant correlation was not
      present between them. So, we suggest that neuropsychological tests are more
      convenient for the assessment of cognitive functions in children with epilepsy
      than the P300 recordings.

PMID- 15862187
TI  - Persistent neocortical astrogliosis in adult wistar rats following prenatal
      ethanol exposure.
AB  - Timed pregnant wistar rats were divided randomly into groups A and B (n=6) each
      and C (n=4). Group A received a daily ethanol dose of 5.8 g/kg body weight per
      day, at 16.00 h on days 9-12th of gestation by intragastric intubations. Group B
      was pair-fed along with the treated rats and received an isocaloric solution of
      sucrose to substitute for the ethanol in the experimental group, for the same
      duration, while group C received standard chow and water ad libitum. The adult
      offsprings at 42 days of age, (n=10) from each group were sacrificed by whole
      body perfusion-fixation, after anaesthesia by an overdose of pentothal
      intraperitoneally. Specimens of neocortical samples were processed routinely for
      paraffin embedding and sections of 6 microm thickness stained for neurohistology.
      Another set of specimens was cryosectioned at -23 degrees C after cryoprotection
      in 30% sucrose/PBS and evaluated for GFAP immunohistochemistry. The study showed
      a distortion of the microanatomy of the neocortex in the treatment group A,
      particularly of layer V pyramidal neurons, which revealed mostly pyknotic
      pyramidal neurons with broken dendrites, collapsed cell bodies, obliterated
      nuclei and nucleoli. No differences were found between the brains from rats in
      groups B and C. There were widespread focal areas of reactive astrogliosis, more
      prominent within the layer V. Astrocytes demonstrated highly stained GFAP
      positive immunoreactivity with heavy fibrillary processes in the neocortex of
      group A offsprings compared to the controls. The sub-pial regions were, however,
      sparse. In conclusion, this study confirms the hypothesis that microanatomical
      and microchemical changes following prenatal ethanol exposure persist into
      adulthood in rats.

PMID- 15862188
TI  - X chromosome inactivation patterns in brain in Rett syndrome: implications for
      the disease phenotype.
AB  - Skewed X chromosome inactivation (XCI) has been implicated in modulating the
      severity of Rett syndrome (RTT), although studies by different groups have
      yielded conflicting results. In this study we have characterised the XCI pattern
      in various neuroanatomical regions of nine RTT brains and non-neural tissue in
      two of these patients to determine whether or not variable XCI patterns occur in
      different brain regions or somatic tissues of the same patient. The mean XCI
      patterns for frontal and occipital cortex were compared between RTT and control
      subjects, and showed no significant differences when comparing RTT frontal to
      control frontal cortex or RTT occipital to control occipital cortex. However, one
      RTT subject displayed variability across the different neuroanatomical regions of
      the brain and skewing in some non-neural tissues. This observation adds another
      dimension to the epigenetic factors that may contribute to the phenotype in RTT.
      It also mandates that caution should be exercised in factoring XCI, including
      assumptions based on the blood XCI pattern, into the development of phenotype
      genotype correlations.

PMID- 15862189
TI  - Delirious behavior in children with influenza: its clinical features and EEG
      findings.
AB  - The clinical characteristics and electroencephalogram (EEG) findings in delirious
      behavior in children with influenza were studied in order to differentiate it
      from influenza-associated encephalitis/encephalopathy. Fifteen consecutive
      children with delirious behavior associated with influenza were investigated.
      Their clinical courses were investigated using medical records. EEG was obtained
      during the delirious behavior, when possible. The body temperature during the
      delirious behavior was 39.0 degrees C or higher in 13 children. A subtle
      reduction of consciousness was observed in 10 children. Seizures were observed in
      five children. EEG revealed some mildly abnormal findings in 13 children,
      including mild slowing of the background activity, insertion of semirhythmic high
      voltage slow waves, and appearance of relatively high voltage semirhythmic theta
      waves. The EEG findings normalized after the delirious behavior had disappeared.
      EEG revealed transient and mild abnormalities in children with delirious behavior
      but without encephalitis/encephalopathy, and thus might be useful for diagnostic
      evaluation in such condition.

PMID- 15862190
TI  - Modification of AMPA receptor properties following environmental enrichment.
AB  - Environmental enrichment results in many modifications in the brain such as
      structural, behavioural, and biochemical changes. alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid (AMPA)-type receptors for excitatory amino acid
      glutamate are recently found to be involved in neuronal plasticity. In this
      study, we examined whether environmental enrichment modified the brain expression
      of mRNA for subunit composition of AMPA receptors in adult mice using the real
      time quantitative PCR method and western blotting. Mice housed in enriched
      environments showed significantly higher levels of GluR2 and GluR4 subunits in
      the hippocampus compared to control mice. We concluded that environmental
      enrichment can change the expression of AMPA receptor subunits and thus might
      modify the potentials of brain plasticity.

PMID- 15862191
TI  - Regional cerebral blood flow in children with ADHD: changes with age.
AB  - The aim of this study was to investigate the changes in regional cerebral blood
      flow (rCBF) with age in patients with attention deficit hyperactivity disorder
      (ADHD). Twenty-nine drug-naive ADHD subjects (24 boys, 5 girls; age 7-13; mean+/
      SD=age 9.2+/-2.1) and 12 subjects with epilepsy (all diagnosed as having complex
      partial seizure, 6 boys, 6 girls; age 7-14; mean+/-SD=8.5+/-2.1) were included in
      the study. All cases of ADHD were diagnosed according to DSM-IV criteria.
      Cerebral blood flow was evaluated with Tc-99m-hexamethylpropyleneamine oxime
      (Tc99m HMPAO) brain single photon emission tomography (SPECT) during standard
      resting condition in all of the cases. Asymmetry indices for each region of
      interest were calculated. Absolute rCBF values were normalized as the absolute
      rCBF values divided by the whole brain absolute value. The prefrontal lobe
      asymmetry indices were significantly negatively correlated with age in ADHD cases
      (r=-0.408, P=0.025), which indicated the increased prefrontal rCBF lateralization
      from the right to the left side with age. When ADHD cases older than 7 years of
      age were compared with those with epilepsy, the ADHD cases had lower right
      prefrontal and frontal rCBF and higher left parietal rCBF. The epilepsy group
      showed no significant correlations between age and asymmetry indices and showed a
      different developmental trajectory for prefrontal asymmetry and right prefrontal
      rCBF values. The results indicated that the left hemisphere dominance in the
      prefrontal cortex significantly increases with age in ADHD cases.

PMID- 15862192
TI  - Zonisamide for West syndrome: a comparison of clinical responses among different
      titration rate.
AB  - We administered zonisamide (ZNS) to patients with West syndrome in different
      titration protocols and compared their short-term therapeutic effects. We
      designed three protocols to raise the serum ZNS concentration (SZC): (1) increase
      the dose in three steps, from 3 to 10 mg/kg every 3 days, (2) increase the dose
      from 5 to 10 mg/kg over 3-7 days, and (3) start with 10 mg/kg and maintain this
      dosage for 2 weeks. The subjects were 23 infants with West syndrome, 8 of whom
      comprised the 1st group, 5 the 2nd group, and the remaining 10, the 3rd group. As
      a result, excellent and good effects were obtained in a total of seven patients
      (30.4%) and one patient, respectively (1/8 in the 1st step-up group, 3/5 in the
      2nd step-up group, and 4/10 in the 3rd group). The maximum SZC was higher in the
      excellent and good effect groups (n=8; 32.0+/-8.0 microg/ml) than in the
      ineffective group (n=15; 22.4+/-8.2 microg/ml) (P<0.05). The period of time
      required for cessation of spasms appeared shorter in the 3rd group (n=4; mean=5.7
      days) than in the 1st and 2nd groups (n=4; mean=10.3 days). There were few side
      effects except for transient hyperthermia and gastrointestinal symptoms. Our new
      protocol of starting with 10 mg/kg of ZNS can be introduced safely and make a
      therapeutic judgment feasible within 2 weeks.

PMID- 15862193
TI  - Brain magnetic resonance image changes in a family with congenital and classic
      myotonic dystrophy.
AB  - We present the clinical manifestations, brain magnetic resonance images (MRI),
      and genetic analysis of a family with 2 siblings with congenital myotonic
      dystrophy type 1 (DM1) and 4 patients with classic DM1. These 2 patients with
      congenital DM1 had severe mental retardation and a characteristic feature of
      hyperintensity of white matter at the posterior-superior trigone (HWMPST), in
      addition to ventricular dilatation in T2-weighted images (T2WI) of brain MRI. In
      2 of the 4 classic DM1 patients, brain T2WI MRI showed hyperintensity lesions in
      the bilateral frontal and/or temporal regions, which were absent in congenital
      DM1. In conclusion, we suggest that the HWMPST in brain MRI is a characteristic
      finding in congenital DM1, and that the severe cognitive impairments are not only
      attributable to the subcortical white matter lesions. In congenital DM1, the
      cognitive function is a diffuse impairment, which is different from that in
      classic DM1.

PMID- 15862194
TI  - The effects of copper-histidine therapy on brain metabolism in a patient with
      Menkes disease: a proton magnetic resonance spectroscopic study.
AB  - We report on metabolic changes in the brain of a boy with Menkes disease. He was
      treated with parenteral copper (Cu)-histidine supplementation, from 5 months of
      age, and assessed with proton magnetic resonance spectroscopy ((1)H-MRS). The
      single-voxel (1)H-MRS before treatment revealed an accumulation of lactate and a
      reduced N-acetyl aspartate (NAA)/total creatine (tCr) ratio with a z-score of 
      3.0. During treatment, the lactate signal faded away, whereas the NAA signal
      gradually increased to a z-score of -1.5 at 120 days of treatment. The
      choline/tCr ratio did not deviate much initially (z-score +0.5), but the ratio
      increased markedly during treatment (z-score +4.8). Consequently, the Cu
      histidine therapy initiated after the critical period still improved the neuronal
      metabolism, suggesting that some Cu was delivered to neurons. Nevertheless, the
      brain atrophy, impaired myelination, and severe neurological symptoms were not
      ameliorated.

PMID- 15862195
TI  - Long-term follow-up of a patient with subacute sclerosing panencephalitis
      successfully treated with intrathecal interferon alpha.
AB  - To clarify long-term effects of intrathecal administration of interferon (IFN)
      alpha in subacute sclerosing panencephalitis (SSPE), we followed up a patient
      with SSPE for 18 years, who had been treated successfully using intrathecal IFN
      alpha with response-based dose adjustments. IFN-alpha therapy dramatically
      induced remission of disease and greatly improved quality of life for 7-8 years,
      but this was followed by severely deterioration with decorticate posturing and
      akinetic mutism. Thus, IFN-alpha-induced remission appears most likely to be
      temporary, even when an SSPE patient shows an excellent initial response. To
      improve long-term outcome for SSPE patients, more effective therapy is needed.

PMID- 15862196
TI  - Postinfectious immune-mediated encephalitis after pediatric herpes simplex
      encephalitis.
AB  - We report a 3-year-old patient who presented a secondary acute neurological
      deterioration clinically characterized by a partial Kluver-Bucy syndrome, 1 month
      after the onset of herpes simplex encephalitis. This episode is unlikely due to
      continuation or resumption of cerebral viral replication but might be related to
      an immune-inflammatory process. In children, postinfectious immune-mediated
      encephalitis occurring after HSE are usually clinically characterized by
      choreoathetoid movements. This type of movement disorder was, however, not
      observed in this patient. On the basis of this case and a review of the
      literature, we hypothesize the existence of a spectrum of secondary immune
      mediated process triggered by herpes simplex virus cerebral infection ranging
      from asymptomatic cases with diffuse white matter involvement to secondary acute
      neurological deteriorations with or without extrapyramidal features.

PMID- 15862197
TI  - Merosin-negative congenital muscular dystrophy: magnetic resonance spectroscopy
      findings.
AB  - Congenital muscular dystrophies (CMD) are heterogeneous group of muscle disorders
      with autosomal recessive inheritance. Merosin deficiency has been identified in
      some patients with CMD all of whom also had white matter abnormalities on MRI. In
      postmortem studies, the brain showed extensive myelin pallor with a spongy
      appearance of white matter and moderate astrocytosis or demyelination. Direct
      assessment of neuropathologic aspects of MN-CMD such as demyelination is possible
      with MR spectroscopy (MRS). Although previous reports have described several
      neuro-imaging findings of this disease, MRS findings have not been reported in
      literature. In this case, we report MRS features of a 4-year old girl with MN
      CMD. MRS of brain demonstrated that N-acetylaspartate (NAA)/Creatine (Cr) ratio
      was normal. Increased Choline (Cho)/Cr and Myo-inositol (MI)/Cr ratios were
      obtained. These findings were interpreted as demyelination and gliosis of white
      matter.

PMID- 15862198
TI  - Clinical presentation, EEG studies, and novel mutations in two cases of GLUT1
      deficiency syndrome in Japan.
AB  - We report the first two Japanese children diagnosed with glucose transporter type
      1 (GLUT1) deficiency syndrome. Both boys had been treated under the initial
      diagnosis of epilepsy and were reinvestigated for previously unexplainable
      hypoglycorrhachia. Myoclonic seizures developed at 4 months of age in Patient #1
      (7 years old), and at 2 months of age in Patient #2 (11 years old), followed by
      cerebellar ataxia, spastic diplegia, and mental retardation. Both patients had
      hypoglycorrhachia, and the symptoms were more severe in the latter. CSF and serum
      glucose levels determined simultaneously showed a CSF/serum glucose ratio of
      below 0.4 in both patients. In mildly affected Patient #1, the postprandial
      waking EEG showed improvement in the background activity, as compared to that
      recorded after overnight fasting, while no significant changes were observed in
      severely affected Patient #2. In both patients, the functional GLUT1 defect was
      confirmed by 3-O-methyl-D-glucose uptake into erythrocytes. Molecular analyses
      identified heterozygous novel mutations in both patients, within exons 6 and 2 of
      the GLUT1 gene, respectively. The ketogenic diet was refused in Patient #1, but
      started in Patient #2 with significant clinical benefit. Fasting CSF analysis and
      pre-/postprandial EEG changes in children with epileptic seizures and
      unexplainable neurological deterioration help in diagnosing this potentially
      treatable disorder.

PMID- 15862199
TI  - Visualizing human brain surface from T1-weighted MR images using texture-mapped
      triangle meshes.
AB  - We describe a novel method for visualizing brain surface from anatomical magnetic
      resonance images (MRIs). The method utilizes standard 2D texture mapping
      capabilities of OpenGL graphics language. It combines the benefits of volume
      rendering and triangle-mesh rendering, allowing fast and realistic-looking brain
      surface visualizations. Consequently, relatively low-resolution triangle meshes
      can be used while the texture images provide the necessary details. The mapping
      is optimized to provide good texture-image resolution for the triangles with
      respect to their original sizes in the 3D MRI volume. The actual 2D texture
      images are generated by depth integration from the original MRI data. Our method
      adapts to anisotropic voxel sizes without any need to interpolate the volume data
      into cubic voxels, and it is very well suited for visualizing brain anatomy from
      standard T(1)-weighted MR images. Furthermore, other OpenGL objects and
      techniques can be easily combined, for example, to use cut planes, to show other
      surfaces and objects, and to visualize functional data in addition to the
      anatomical information.

PMID- 15862200
TI  - The missing link: analogous human and primate cortical gamma oscillations.
AB  - Recent animal studies highlighting the relationship between functional imaging
      signals and the underlying neuronal activity have revealed the potential
      capabilities of non-invasive methods. However, the valuable exchange of
      information between animal and human studies remains restricted by the limited
      evidence of direct physiological links between species. In this study we used
      magnetoencephalography (MEG) to investigate the occurrence of 30-70 Hz (gamma)
      oscillations in human visual cortex, induced by the presentation of visual
      stimuli of varying contrast. These oscillations, well described in the animal
      literature, were observed in retinotopically concordant locations of visual
      cortex and show striking similarity to those found in primate visual cortex using
      surgically implanted electrodes. The amplitude of the gamma oscillations
      increases linearly with stimulus contrast in strong correlation with the gamma
      oscillations found in the local field potential (LFP) of the macaque. We
      demonstrate that non-invasive magnetic field measurements of gamma oscillations
      in human visual cortex concur with invasive measures of activation in primate
      visual cortex, suggesting both a direct representation of underlying neuronal
      activity and a concurrence between human and primate cortical activity.

PMID- 15862201
TI  - Automated cortical projection of head-surface locations for transcranial
      functional brain mapping.
AB  - Recent advancements in two noninvasive transcranial neuroimaging techniques, near
      infrared spectroscopy (NIRS) and transcranial magnetic stimulation (TMS), signify
      the increasing importance of establishing structural compatibility between
      transcranial methods and conventional tomographic methods, such as functional
      magnetic resonance imaging (fMRI) and positron emission tomography (PET). The
      transcranial data obtained from the head surface should be projected onto the
      cortical surface to present the transcranial brain-mapping data on the same
      platform as tomographic methods. Thus, we developed two transcranial projection
      algorithms that project given head-surface points onto the cortical surface in
      structural images, and computer programs based on them. The convex-hull algorithm
      features geometric handling of the cortical surface, while the balloon-inflation
      algorithm is faster, and better reflects the local cortical structure. The
      automatic cortical projection methods proved to be as effective as the manual
      projection method described in our previous study. These methods achieved perfect
      correspondence between any given point on the head surface or a related nearby
      point in space, and its cortical projection point. Moreover, we developed a
      neighbor-reference method that enables transcranial cortical projection of a
      given head-surface point in reference to three neighboring points and one
      additional standard point, even when no structural image of the subject is
      available. We also calculated an error factor associated with these probabilistic
      estimations. The current study presents a close topological link between
      transcranial and tomographic brain-mapping modalities, which could contribute to
      inter-modal data standardization.

PMID- 15862202
TI  - Functional MRI shows activation of the medial preoptic area during sleep.
AB  - Changes in the activity of the basal forebrain sleep regulating areas were
      studied noninvasively in conscious rats by employing functional magnetic
      resonance imaging (fMRI). Sleep-wakefulness (S-W) stages were identified with the
      help of electrophysiological recordings carried out simultaneously. An increase
      in the signal intensity was observed in the medial preoptic area (mPOA) during
      sleep indicating a heightened activity of neurons in this area. In some rats,
      there was a decrease in the activity of the fronto-parietal cortex. The sleep
      induced increase in activity in the mPOA and decrease in the fronto-parietal
      cortex are in relation to their levels in the awake state. The findings helped to
      localize the critical area for the maintenance of slow wave sleep at the mPOA.
      These results further corroborate some of the previous suggestions based on
      neurotoxic lesion, chemical stimulation and electrophysiological recordings.

PMID- 15862203
TI  - Age-dependent brain activation during forward and backward digit recall revealed
      by fMRI.
AB  - In this study, brain activation associated with forward and backward digit recall
      was examined in healthy old and young adults using functional MRI. A number of
      areas were activated during the recall. In young adults, greater activation was
      found in the left prefrontal cortex (BA9) and the left occipital visual cortex
      during backward digit recall than forward digit recall. In contrast, the
      activation in the right inferior frontal gyrus (BA 44/45) was more extensive in
      forward digit recall than in backward digit recall. In older adults, backward
      recall generated stronger activation than forward recall in most areas, including
      the frontal, the parietal, the occipital, and the temporal cortices. In the
      backward recall condition, the right inferior frontal gyrus (BA44/45) showed more
      activation in the old group than in the young group. These results suggest that
      different neural mechanisms may be involved in forward and backward digit recall
      and brain functions associated with these two types of recall are differentially
      affected by aging.

PMID- 15862204
TI  - Nociceptive and non-nociceptive sub-regions in the human secondary somatosensory
      cortex: an MEG study using fMRI constraints.
AB  - Previous evidence from functional magnetic resonance imaging (fMRI) has shown
      that a painful galvanic stimulation mainly activates a posterior sub-region in
      the secondary somatosensory cortex (SII), whereas a non-painful sensory
      stimulation mainly activates an anterior sub-region of SII [Ferretti, A.,
      Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L., Rossini, P.M.,
      Romani, G.L., 2003. Functional topography of the secondary somatosensory cortex
      for non-painful and painful stimuli: an fMRI study. Neuroimage 20 (3), 1625
      1638.]. The present study, combining fMRI with magnetoencephalographic (MEG)
      findings, assessed the working hypothesis that the activity of such a posterior
      SII sub-region is characterized by an amplitude and temporal evolution in line
      with the bilateral functional organization of nociceptive systems. Somatosensory
      evoked magnetic fields (SEFs) recordings after alvanic median nerve stimulation
      were obtained from the same sample of subjects previously examined with fMRI
      [Ferretti, A., Babiloni, C., Del Gratta, C., Caulo, M., Tartaro, A., Bonomo, L.,
      Rossini, P.M., Romani, G.L., 2003. Functional topography of the secondary
      somatosensory cortex for non-painful and painful stimuli: an fMRI study.
      Neuroimage 20 (3), 1625-1638.]. Constraints for dipole source localizations
      obtained from MEG recordings were applied according to fMRI activations, namely,
      at the posterior and the anterior SII sub-regions. It was shown that, after
      painful stimulation, the two posterior SII sub-regions of the contralateral and
      ipsilateral hemispheres were characterized by dipole sources with similar
      amplitudes and latencies. In contrast, the activity of anterior SII sub-regions
      showed statistically significant differences in amplitude and latency during both
      non-painful and painful stimulation conditions. In the contralateral hemisphere,
      the source activity was greater in amplitude and shorter in latency with respect
      to the ipsilateral. Finally, painful stimuli evoked a response from the posterior
      sub-regions peaking significantly earlier than from the anterior sub-regions.
      These results suggested that both ipsi and contra posterior SII sub-regions
      process painful stimuli in parallel, while the anterior SII sub-regions might
      play an integrative role in the processing of somatosensory stimuli.

PMID- 15862205
TI  - Assessment of in vivo MR imaging compared to physical sections in vitro--a
      quantitative study of brain volumes using stereology.
AB  - The object of the present study was to compare stereological estimates of brain
      volumes obtained in vivo by magnetic resonance imaging (MRI) to corresponding
      volumes from physical sections in vitro. Brains of ten domestic pigs were imaged
      using a 3-T scanner. The volumes of different brain compartments were obtained
      from MR images by two observers and from physical sections using the Cavalieri
      estimator in combination with point counting. Paired t tests revealed no
      significant differences between the two methods for any of the five compartments
      considered, except for the basal gray compartment. However, although
      intraobserver difference of MRI estimates was acceptable, the interobserver
      difference was not. A statistical highly significant difference of 11-41% was
      observed between observers for volume estimates of all compartments considered.
      The study demonstrates that quantitative MRI is susceptible to observer dependent
      interpretation of images.

PMID- 15862206
TI  - Superior temporal and inferior frontal cortices are activated by infrequent sound
      duration decrements: an fMRI study.
AB  - Functional magnetic resonance imaging (fMRI) was used to examine the processing
      of infrequent changes occurring in an unattended sound sequence. In event-related
      brain potentials (ERPs), such sound changes typically elicit several responses,
      including an enhanced N1, the mismatch negativity (MMN), and the P3a. In the
      present study, subjects were presented with a repeating sound of 75 ms in
      duration, which was occasionally replaced, in separate blocks, by a 15-ms, 25-ms,
      or 35-ms sound (large, medium, and small change, respectively). In the baseline
      block, only the frequent 75-ms sound was presented. During the scanning, the
      subjects were instructed to ignore the sounds while watching a silent wildlife
      documentary. We assumed that in this condition, the MMN mechanism would
      contribute more to the observed activation than the other change-related
      processes. We expected sound changes to elicit fMRI activation bilaterally in the
      supratemporal cortices, where the electric MMN is mainly generated, and that the
      magnitude of this activation would increase with the magnitude of sound duration
      change. Unexpectedly, however, we found that only blocks with medium duration
      changes (25 ms) showed significant activation in the supratemporal cortex. In
      addition, as reported in some previous EEG and fMRI studies, contrasts between
      different levels of sound duration change revealed additional activation in the
      inferior frontal cortex bilaterally. This activation tended to be greater for the
      small and medium changes than for the large ones.

PMID- 15862207
TI  - Linking retinotopic fMRI mapping and anatomical probability maps of human
      occipital areas V1 and V2.
AB  - Using functional MRI, we characterized field sign maps of the occipital cortex
      and created three-dimensional maps of these areas. By averaging the individual
      maps into group maps, probability maps of functionally defined V1 or V2 were
      determined and compared to anatomical probability maps of Brodmann areas BA17 and
      BA18 derived from cytoarchitectonic analysis (Amunts, K., Malikovic, A.,
      Mohlberg, H., Schormann, T., Zilles, K., 2000. Brodmann's areas 17 and 18 brought
      into stereotaxic space-where and how variable? NeuroImage 11, 66-84). Comparison
      of areas BA17/V1 and BA18/V2 revealed good agreement of the anatomical and
      functional probability maps. Taking into account that our functional stimulation
      (due to constraints of the visual angle of stimulation achievable in the MR
      scanner) only identified parts of V1 and V2, for statistical evaluation of the
      spatial correlation of V1 and BA17, or V2 and BA18, respectively, the a priori
      measure kappa was calculated testing the hypothesis that a region can only be
      part of functionally defined V1 or V2 if it is also in anatomically defined BA17
      or BA18, respectively. kappa = 1 means the hypothesis is fully true, kappa = 0
      means functionally and anatomically defined visual areas are independent. When
      applying this measure to the probability maps, kappa was equal to 0.84 for both
      V1/BA17 and V2/BA18. The data thus show a good correspondence of functionally and
      anatomically derived segregations of early visual processing areas and serve as a
      basis for employing anatomical probability maps of V1 and V2 in group analyses to
      characterize functional activations of early visual processing areas.

PMID- 15862208
TI  - Magnetic resonance imaging at microscopic resolution reveals subtle morphological
      changes in a mouse model of dopaminergic hyperfunction.
AB  - Structural abnormalities of the basal ganglia have been documented in several
      neuropsychiatric conditions associated with dysregulation of the dopamine system.
      However, the histological nature underlying these changes is largely unknown.
      Using magnetic resonance imaging at microscopic resolution (MRI, 9.4 T with 43
      microm isotropic spatial resolution) and stereological techniques, we have
      investigated the effect of increased dopamine neurotransmission on brain
      morphology in mice with elevated extracellular dopamine, the dopamine transporter
      knockout (DAT-KO) mice. We first demonstrate the usefulness of MRI at microscopic
      resolution for the accurate identification and measurement of volumes of specific
      subregions, accounting for less than 0.03% (0.16 mm(3)) of the volume of a mouse
      brain. Furthermore, the MRI analysis reveals a significantly lower volume (-9%)
      of the anterior striatum of DAT-KO mice, while the volume of other dopamine
      related structures such as the posterior striatum and the substantia nigra pars
      reticulata is unchanged in comparison to wild type littermates. Stereological
      analysis performed in the same brains reveals that one important structural
      factor accounting for this selective change in volume is a reduction of 18% in
      the absolute number of neuronal cell bodies. The feasibility of assessing
      accurately small morphological alterations in mouse models, where the molecular
      and histological pathologies can be easily compared in a controlled manner,
      provides a paradigm to examine the relevance of selective brain volumetric
      changes associated with a number of neuropathological conditions.

PMID- 15862209
TI  - Task-dependent oscillations during unimanual and bimanual movements in the human
      primary motor cortex and SMA studied with magnetoencephalography.
AB  - The neural mechanisms subserving uni- and bimanual control of movements are not
      well understood. Nevertheless, recent studies indicate a functional role of
      oscillatory activity in movement control and point towards a hemispheric
      asymmetry in motor control. This study specifically addresses the issues of (i)
      task-relatedness, (ii) hemispheric symmetry, and (iii) frequency specificity of
      the measures power, cerebro-muscular coherence, and cerebro-cerebral coherence in
      bilateral primary motor cortex and supplementary motor area (SMA). We have
      studied 10 right-handed subjects with simultaneous recordings of
      magnetoencephalography and surface electromyography during different unimanual
      and bimanual tasks. Using the analysis technique Dynamic Imaging of Coherent
      Sources (DICS), left and right primary motor cortex and SMA were functionally
      localized. Power, cerebro-musclar coherence, and cerebro-cerebral coherence
      between these areas were computed for four frequency bands in each condition and
      subjected to ANOVA. Results show a task-specific modulation of power and
      coherence, and further indicate a hemispheric asymmetry in the control of
      unimanual and bimanual movements. In addition, different frequency bands showed
      different task-dependent variations. The gamma band (26-40 Hz) showed strongest
      modulation for cerebro-muscular coherence and was strongest for the isometric
      contraction conditions. In contrast, the beta band (13-24 Hz) showed the
      strongest variations between static and dynamic conditions, and seems to play a
      particular role in movement control. In summary, our results indicate a
      differential functional role of oscillatory activity and coupling in the motor
      system.

PMID- 15862210
TI  - Increased sensitivity in neuroimaging analyses using robust regression.
AB  - Robust regression techniques are a class of estimators that are relatively
      insensitive to the presence of one or more outliers in the data. They are
      especially well suited to data that require large numbers of statistical tests
      and may contain outliers due to factors not of experimental interest. Both these
      issues apply particularly to neuroimaging data analysis. We use simulations to
      compare several robust techniques against ordinary least squares (OLS)
      regression, and we apply robust regression to second-level (group "random
      effects") analyses in three fMRI datasets. Our results show that robust
      iteratively reweighted least squares (IRLS) at the 2nd level is a computationally
      efficient technique that both increases statistical power and decreases false
      positive rates in the presence of outliers. The benefits of IRLS are apparent
      with small samples (n = 10) and increase with larger sample sizes (n = 40) in the
      typical range of group neuroimaging experiments. When no true effects are
      present, IRLS controls false positive rates at an appropriate level. We show that
      IRLS can have substantial benefits in analysis of group data and in estimating
      hemodynamic response shapes from time series data. We provide software to
      implement IRLS in group neuroimaging analyses.

PMID- 15862211
TI  - An electroencephalographic fingerprint of human sleep.
AB  - Homeostatic and circadian processes are basic mechanisms of human sleep which
      challenge the common knowledge of large individual variations in sleep need or
      differences in circadian types. However, since sleep research has mostly focused
      on group measures, an approach which emphasizes the similarities between
      subjects, the biological foundations of the individual differences in normal
      sleep are still poorly understood. In the present work, we assessed individual
      differences in a range of EEG frequencies including sigma activity during non-REM
      sleep (8.0-15.5 Hz range) in a group of 10 subjects who had participated in a
      slow-wave sleep (SWS) deprivation study. We showed that, like a "fingerprint", a
      particular topographic distribution of the electroencephalogram (EEG) power along
      the antero-posterior cortical axis distinguishes each individual during non-REM
      sleep. This individual EEG-trait is substantially invariant across six
      consecutive nights characterized by large experimentally induced changes of sleep
      architecture. One possible hypothesis is that these EEG invariances can be
      related to individual differences in genetically determined functional brain
      anatomy, rather than to sleep-dependent mechanisms.

PMID- 15862212
TI  - Association of human hippocampal neurochemistry, serotonin transporter genetic
      variation, and anxiety.
AB  - The impact of the serotonin transporter (5-HTT) gene-linked polymorphic region (5
      HTTLPR) on anxiety-related behavior and related cerebral activation has
      facilitated the understanding of neurobiological mechanisms of anxiety. However,
      the influence of the 5-HTTLPR genotype on hippocampal neuronal development and
      neurochemistry, which is relevant to anxiety behavior, has not been investigated.
      In 38 healthy subjects, absolute concentrations of N-acetylaspartate (NAA) were
      measured as a main surrogate parameter for hippocampal neurochemistry on a 3-T
      scanner. A significantly lower hippocampal NAA concentration in s allele carriers
      was observed as compared to l/l genotype. Other metabolites (choline, creatine +
      phosphocreatine, glutamate) were unaffected by genotype. The hippocampal NAA
      concentration was negatively correlated with trait anxiety scores (STAI).
      Metabolites measured in the anterior cingulate cortex (reference region) were not
      associated with genotype. The results are in accordance with the recently
      reported relationship between hippocampal neuronal development and anxiety
      behavior in adult animals and show an association between human limbic
      neurochemistry and genetically driven serotonergic neurotransmission relevant to
      anxiety.

PMID- 15862213
TI  - Demyelination increases radial diffusivity in corpus callosum of mouse brain.
AB  - Myelin damage, as seen in multiple sclerosis (MS) and other demyelinating
      diseases, impairs axonal conduction and can also be associated with axonal
      degeneration. Accurate assessments of these conditions may be highly beneficial
      in evaluating and selecting therapeutic strategies for patient management.
      Recently, an analytical approach examining diffusion tensor imaging (DTI) derived
      parameters has been proposed to assess the extent of axonal damage,
      demyelination, or both. The current study uses the well-characterized cuprizone
      model of experimental demyelination and remyelination of corpus callosum in mouse
      brain to evaluate the ability of DTI parameters to detect the progression of
      myelin degeneration and regeneration. Our results demonstrate that the extent of
      increased radial diffusivity reflects the severity of demyelination in corpus
      callosum of mouse brain affected by cuprizone treatment. Subsequently, radial
      diffusivity decreases with the progression of remyelination. Furthermore, radial
      diffusivity changes were specific to the time course of changes in myelin
      integrity as distinct from axonal injury, which was detected by betaAPP
      immunostaining and shown to be most extensive prior to demyelination. Radial
      diffusivity offers a specific assessment of demyelination and remyelination, as
      distinct from acute axonal damage.

PMID- 15862214
TI  - Pathways for fear perception: modulation of amygdala activity by thalamo-cortical
      systems.
AB  - Effective perception of fear signals is crucial for human survival and the
      importance of the amygdala in this process is well documented. Animal, lesion and
      neuroimaging studies indicate that incoming sensory signals of fear travel from
      thalamus to amygdala via two neural pathways: a direct subcortical route and an
      indirect pathway via the sensory cortex. Other lines of research have
      demonstrated prefrontal modulation of the amygdala. However, no study to date has
      examined the prefrontal modulation of the thalamo-cortico-amygdala pathways in
      vivo. We used psychophysiological and physiophysiological interactions to examine
      the functional connectivity within thalamus, amygdala and sensory (inferior
      occipital, fusiform) cortices, and the modulation of these networks by the
      anterior cingulate cortex (ACC). Functional magnetic resonance imaging (fMRI)
      data were acquired for 28 healthy control subjects during a fear perception task,
      with neutral as the 'baseline' control condition. Main effect analysis, using a
      region of interest (ROI) approach, confirmed that these regions are part of a
      distributed neural system for fear perception. Psychophysiological interactions
      revealed an inverse functional connectivity between occipito-temporal visual
      regions and the left amygdala, but a positive connectivity between these visual
      region and the right amygdala, suggesting that there is a hemispheric
      specialization in the transfer of fear signals from sensory cortices to amygdala.
      Physiophysiological interactions revealed a dorsal-ventral division in ACC
      modulation of the thalamus-sensory cortex pathway. While the dorsal ACC showed a
      positive modulation of this pathway, the ventral ACC exhibited an inverse
      relationship. In addition, both the dorsal and ventral ACC showed an inverse
      interaction with the direct thalamus-amygdala pathway. These findings suggest
      that thalamo-amygdala and cortical regions are involved in a dynamic interplay,
      with functional differentiation in both lateralized and ventral/dorsal gradients.
      Breakdowns in these interactions may give rise to affect-related symptoms seen in
      a range of neuropsychiatric disorders.

PMID- 15862215
TI  - Two electrophysiological stages of spatial orienting towards fearful faces: early
      temporo-parietal activation preceding gain control in extrastriate visual cortex.
AB  - Visuo-spatial attention tends to be prioritized towards emotionally negative
      stimuli such as fearful faces, as opposed to neutral or positive stimuli. Using a
      covert orienting task, we previously showed that a lateral occipital P1
      component, with extrastriate neural sources, was selectively enhanced to
      lateralized visual targets replacing a fearful face (fear-valid trial) than the
      same targets replacing a neutral face (fear-invalid trial), providing evidence
      for exogenous spatial orienting of attention towards threat cues. Here, we
      describe a new analysis of these data, using topographic evoked potentials
      mapping methods combined with a distributed source localization technique. We
      show that an early field topography (40-80 ms post-target onset) with a centro
      parietal negativity and a left posterior parietal source distinguished fear-valid
      from fear-invalid trials, whereas a distinct activity with anterior cingulate
      sources was selectively evoked during fear-invalid trials. At the same latency,
      or later, no difference in field topography was found for valid compared to
      invalid trials with happy faces. The early parietal map preceded a modulation in
      amplitude of the field strength (approximately 130 ms), corresponding to the
      enhanced lateral occipital P1 during valid trials in the fear condition.
      Furthermore, this early topography at 40-80 ms was positively correlated with the
      subsequent amplitude modulation of P1 at 130-160 ms in the fear condition,
      suggesting a possible functional coupling between these two successive events.
      These data have important implications for models of spatial attention and
      interactions with emotion. They suggest two successive stages of neural activity
      during exogenous orienting of attention towards visual targets following fearful
      faces, including an early posterior parietal negativity, followed by gain control
      mechanisms enhancing visual responses in extrastriate occipital cortex.

PMID- 15862216
TI  - Frequency specific changes in regional cerebral blood flow and motor system
      connectivity following rTMS to the primary motor cortex.
AB  - Repetitive transcranial magnetic stimulation (rTMS) to the human primary motor
      cortex (M1) causes bidirectional changes in corticospinal excitability depending
      on the stimulation frequency used. We used functional brain imaging to compare
      the effects of 5 Hz and 1 Hz-rTMS on local and inter-regional connectivity within
      the motor system. Regional cerebral blood flow (rCBF) was measured as a marker of
      synaptic activity at rest and during freely selected finger movements. We
      hypothesized that increased cortical excitability induced by 5 Hz-rTMS over M1
      has an opposite effect on the synaptic activity and the connectivity of the motor
      network from the decreased cortical excitability induced by 1 Hz-rTMS. rTMS at
      both frequencies induced similar changes in rCBF at the site of stimulation and
      within areas of the motor network engaged by the task. The two frequencies showed
      different effects on movement-related coupling between motor areas. Connectivity
      analyses also indicated a differential effect of 5 and 1 Hz-rTMS on motor network
      connectivity, suggesting a role for an inferomedial portion of left M1 and left
      dorsal premotor cortex in maintaining performance. These results suggest that
      rapid reorganization of the motor system occurs to maintain task performance
      during periods of altered cortical excitability. This reorganization differs
      according to the modulation of excitability which is a function of rTMS
      frequency. This study extends the work of Lee et al. (Lee, L., Siebner, H.R.,
      Rowe, J.B., Rizzo, V. Rothwell, J.C. Frackowiak, R.S. Friston, K.J., 2003. Acute
      remapping within the motor system induced by low-frequency repetitive
      transcranial magnetic stimulation. J. Neurosci. 23, 5308-5318.) by providing
      evidence that the pattern of acute reorganization in the motor network following
      rTMS depends on the direction of conditioning.

PMID- 15862217
TI  - Coherence between fMRI time-series distinguishes two spatial working memory
      networks.
AB  - Widespread and distributed brain regions are thought to form networks that
      together support working memory. We recently demonstrated that different cortical
      areas maintain relatively different codes across a memory delay (Curtis et. al.,
      J Neurosci, 2004; 24:3944-3952). The frontal eye fields (FEF), for example, were
      more active during the delay when the direction of the memory-guided saccade was
      known compared to when it was not known throughout the delay. Other areas showed
      the opposite pattern. Despite these task-dependent differences in regional
      activity, we could only assume but not address the functional interactions
      between the identified nodes of the putative network. Here, we use a bivariate
      technique, coherence, to formally characterize functional interactions between a
      seed region and other brain areas. We find that the type of representational
      codes that are being maintained in working memory biases frontal-parietal
      interactions. For example, coherence between FEF and other oculomotor areas was
      greater when a motor representation was an efficient strategy to bridge the delay
      period. However, coherence between the FEF and higher-order heteromodal areas,
      e.g., dorsolateral prefrontal cortex, was greater when a sensory representation
      must be maintained in working memory.

PMID- 15862218
TI  - Brain activation of lower extremity movement in chronically impaired stroke
      survivors.
AB  - Lower extremity paresis poses significant disability to chronic stroke survivors.
      Unlike for the upper extremity, cortical adaptations in networks controlling the
      paretic leg have not been characterized after stroke. Here, the hypotheses are
      that brain activation associated with unilateral knee movement in chronic stroke
      survivors is abnormal, depends on lesion location, and is related to walking
      ability. Functional magnetic resonance imaging of unilateral knee movement was
      obtained in 31 patients 26.9 months (mean, IQ range: 11.3-68.1) after stroke and
      in 10 age-matched healthy controls. Strokes were stratified according to lesion
      location. Locomotor disability (30 ft walking speed) did not differ between
      patient groups (9 cortical, 12 subcortical, 10 brainstem lesions). Significant
      differences in brain activation as measured by voxel counts in 10 regions of
      interest were found between controls and patients with brainstem (P = 0.006) and
      cortical strokes (P = 0.002), and between subcortical and cortical patients (P =
      0.026). Statistical parametric mapping of data per group revealed similar
      activation patterns in subcortical patients and controls with recruitment of
      contralateral primary motor cortex (M1), supplementary motor area (SMA), and
      bilateral somatosensory area 2 (S2). Cortical recruitment was reduced in
      brainstem and cortical stroke. Better walking was associated with lesser
      contralateral sensorimotor cortex activation in brainstem, but stronger
      recruitment of ipsilateral sensorimotor and bilateral somatosensory cortices in
      subcortical and cortical patients, respectively. A post hoc comparison of
      brainstem patients with and without mirror movements (50%) revealed lesser
      recruitment of ipsilateral cerebellum in the latter. Subcortical patients with
      mirror movements (58%) showed lesser bilateral sensorimotor cortex activation. No
      cortical patient had mirror movements. The data reveal adaptations in networks
      controlling unilateral paretic knee movement in chronic stroke survivors. These
      adaptations depend on lesion location and seem to have functional relevance for
      locomotion.

PMID- 15862220
TI  - Same or different? Neural correlates of happy and sad mood in healthy males.
AB  - Emotional experience in healthy men has been shown to rely on a brain network
      including subcortical as well as cortical areas in a complex interaction, which
      may be substantially influenced by many internal personal and external factors
      such as individuality, gender, stimulus material and task instructions. The
      divergent results may be interpreted by taking these considerations into account.
      Hence, many aspects remain to be clarified in characterizing the neural
      correlates underlying the subjective experience of emotion. One unresolved
      question refers to the influence of emotion quality on the cerebral substrates.
      Hence, 26 male healthy subjects were investigated with functional magnetic
      resonance imaging during standardized sad and happy mood induction as well as a
      cognitive control task to explore brain responses differentially involved in
      positive and negative emotional experience. Sad and happy mood in contrast to the
      control task produced similarly significant activations in the amygdala
      hippocampal area extending into the parahippocampal gyrus as well as in the
      prefrontal and temporal cortex, the anterior cingulate, and the precuneus.
      Significant valence differences emerged when comparing both tasks directly. More
      activation has been demonstrated in the ventrolateral prefrontal cortex (VLPFC),
      the anterior cingulate cortex (ACC), the transverse temporal gyrus, and the
      superior temporal gyrus during sadness. Happiness, on the other hand, produced
      stronger activations in the dorsolateral prefrontal cortex (DLPFC), the cingulate
      gyrus, the inferior temporal gyrus, and the cerebellum. Hence, negative and
      positive moods reveal distinct cortical activation foci within a common neural
      network, probably making the difference between qualitatively different emotional
      feelings.

PMID- 15862219
TI  - DTI tractography based parcellation of white matter: application to the mid
      sagittal morphology of corpus callosum.
AB  - Morphology of the corpus callosum (CC) at the mid-sagittal level has been a
      target of extensive studies. However, the lack of internal structures and its
      polymorphism make it a challenging task to quantitatively analyze shape
      differences among subjects. In this paper, diffusion tensor Imaging (DTI) and
      tract tracing technique were applied to incorporate cortical connectivity
      information to the morphological study. The CC was parcellated into six major
      subdivisions based on trajectories to different cortical areas. This subdivision
      was performed for eight normal subjects and one stroke patient. The parcellated
      CCs of the normal subjects were normalized for morphological analysis. When
      comparing the stroke patient to the normal population, we detected significant
      atrophy in the motor and sensory areas of the patient CC, in line with the
      clinical deficits. This approach provides a new tool to investigate callosal
      morphology and functional relationships.

PMID- 15862221
TI  - Near-infrared spectroscopy (NIRS) in cognitive neuroscience of the primate brain.
AB  - We describe the use of near-infrared spectroscopy (NIRS) as a suitable means of
      assessing hemodynamic changes in the cerebral cortex of awake and behaving
      monkeys. NIRS can be applied to animals performing cognitive tasks in conjunction
      with electrophysiological methods, thus offering the possibility of investigating
      cortical neurovascular coupling in cognition. Because it imposes fewer
      constraints on behavior than fMRI, NIRS appears more practical than fMRI for
      certain studies of cognitive neuroscience on the primate cortex. In the present
      study, NIRS and field potential signals were simultaneously recorded from the
      association cortex (posterior parietal and prefrontal) of monkeys performing two
      delay tasks, one spatial and the other non-spatial. Working memory was
      accompanied by an increase in oxygenated hemoglobin mirrored by a decrease in
      deoxygenated hemoglobin. Both the trends and the amplitudes of these changes
      differed by task and by area. Field potential records revealed slow negative
      potentials that preceded the task trials and persisted during their memory
      period. The negativity during that period was greater in prefrontal than in
      parietal cortex. Between tasks, the potential differences were less pronounced
      than the hemodynamic differences. The present feasibility study lays the
      groundwork for future correlative studies of cognitive function and neurovascular
      coupling in the primate.

PMID- 15862222
TI  - Who did what to whom? The neural basis of argument hierarchies during language
      comprehension.
AB  - The present fMRI study aimed at identifying neural correlates of the syntax
      semantics interface in language comprehension. This was achieved by examining
      what we refer to as "argument hierarchy construction", i.e., determining which
      participant in a sentence is the "Actor" and which is the "Undergoer" of the
      event expressed by the verb. In order to identify the neural bases of argument
      hierarchy processing, we manipulated three factors known to influence the
      complexity of argument hierarchy construction in German, namely argument order,
      verb class and morphological ambiguity. Increased argument hierarchization
      demands engendered enhanced activation in a network of inferior frontal,
      posterior superior temporal, premotor and parietal areas. Moreover, components of
      this network were differentially modulated by the individual factors. In
      particular, the left posterior superior temporal sulcus showed an enhanced
      sensitivity for morphological information and the syntactic realization of the
      verb-based argument hierarchy, while the activation of the left inferior frontal
      gyrus (pars opercularis) corresponded to linearization demands and was
      independent of morphological information. We therefore argue that, for German,
      posterior superior temporal and inferior frontal regions engage in the extraction
      of actorhood from morphosyntactic structure and in the sequential realization of
      hierarchical interpretive dependencies, respectively.

PMID- 15862223
TI  - Hypofrontality and microvascular dysregulation in remitted late-onset depression
      assessed by functional near-infrared spectroscopy.
AB  - Accumulated evidence suggests the involvement of vascular factors in late-onset
      depression. Late-onset depression has characteristics of poor outcome, cognitive
      decline, and high prevalence rather than early-onset depression. The aim of the
      present study was to determine whether or not the functional hypofrontality--that
      is, hypoperfusion and hypometabolism in the frontal lobes-seen in late-onset
      depression is a trait-dependent abnormality of microvascular regulation. This
      study was conducted on 10 patients with remitted late-onset major depressive
      disorder (MDD) and 10 healthy volunteers matched for vascular factors and
      subcortical, or white matter, hyperintensities (WMH). Using near-infrared
      spectroscopy combined with magnetic resonance imaging, we investigated the
      microvascular reactivity in the prefrontal cortex during a cognitive task and
      during carbon dioxide (CO(2)) inhalation. Activation of the prefrontal cortex
      during the cognitive task was significantly less in patients as compared with
      controls, although task performance was not significantly different between the
      two groups. In the patients, a tendency of negative correlation between the
      reduced prefrontal activation during a cognitive task and the severity of
      hyperintensity in periventricular region was observed. Vasomotor reactivity to
      CO(2) inhalation was significantly lower in the patients than in the controls.
      Although there was no significant association between the activation during the
      cognitive and that during the CO(2) inhalation task, the present results suggest
      that prefrontal microvascular dysregulation as shown by NIRS is involved in the
      pathophysiological basis of functional hypofrontality in late-onset depression.
      This finding will provide a new framework for the development of diagnostic
      methods, treatments, and preventive strategies against late-onset depression.

PMID- 15862224
TI  - Comparison of physiological noise at 1.5 T, 3 T and 7 T and optimization of fMRI
      acquisition parameters.
AB  - Previous studies have shown that under some conditions, noise fluctuations in an
      fMRI time-course are dominated by physiological modulations of the image
      intensity with secondary contributions from thermal image noise and that these
      two sources scale differently with signal intensity, susceptibility weighting
      (TE) and field strength. The SNR of the fMRI time-course was found to be near its
      asymptotic limit for moderate spatial resolution measurements at 3 T with only
      marginal gains expected from acquisition at higher field strengths. In this
      study, we investigate the amplitude of image intensity fluctuations in the fMRI
      time-course at magnetic field strengths of 1.5 T, 3 T, and 7 T as a function of
      image resolution, flip angle and TE. The time-course SNR was a similar function
      of the image SNR regardless of whether the image SNR was modulated by flip angle,
      image resolution, or field strength. For spatial resolutions typical of those
      currently used in fMRI (e.g., 3 x 3 x 3 mm(3)), increases in image SNR obtained
      from 7 T acquisition produced only modest increases in time-course SNR. At this
      spatial resolution, the ratio of physiological noise to thermal image noise was
      0.61, 0.89, and 2.23 for 1.5 T, 3 T, and 7 T. At a resolution of 1 x 1 x 3 mm(3),
      however, the physiological to thermal noise ratio was 0.34, 0.57, and 0.91 for
      1.5 T, 3 T and 7 T for TE near T2*. Thus, by reducing the signal strength using
      higher image resolution, the ratio of physiologic to image noise could be reduced
      to a regime where increased sensitivity afforded by higher field strength still
      translated to improved SNR in the fMRI time-series.

PMID- 15862225
TI  - Forming impressions of people versus inanimate objects: social-cognitive
      processing in the medial prefrontal cortex.
AB  - Recent neuroimaging research has linked the task of forming a "person impression"
      to a distinct pattern of neural activation that includes dorsal regions of the
      medial prefrontal cortex (mPFC). Although this result suggests the
      distinctiveness of social cognition - the processes that support inferences about
      the psychological aspects of other people - it remains unclear whether mPFC
      contributions to this impression formation task were person specific or if they
      would extend to other stimulus targets. To address this unresolved issue,
      participants in the current study underwent fMRI scanning while performing
      impression formation or a control task for two types of target: other people and
      inanimate objects. Specifically, participants were asked to use experimentally
      provided information either to form an impression of a person or an object or to
      intentionally encode the sequence in which the information was presented. Results
      demonstrated that activation in an extensive region of dorsal mPFC was greater
      for impression formation of other people than for all other trial types,
      suggesting that this region specifically indexes the social-cognitive aspects of
      impression formation (i.e., understanding the psychological characteristics of
      another mental agent). These findings underscore the extent to which social
      cognition relies on distinct neural mechanisms.

PMID- 15862226
TI  - A method for obtaining tract-specific diffusion tensor MRI measurements in the
      presence of disease: application to patients with clinically isolated syndromes
      suggestive of multiple sclerosis.
AB  - The aim of this study was to investigate whether neurological symptoms related to
      a specific axonal fiber tract in brain white matter were associated with a higher
      degree of tissue damage in that region, in patients at presentation with
      clinically isolated syndromes (CIS) suggestive of multiple sclerosis. To this
      end, a magnetic resonance imaging (MRI) method to segment and evaluate the fiber
      bundle of interest was implemented, taking care to circumvent the problems caused
      by pathology. Diffusion tensor (DT) MRI tractography was used to construct, from
      healthy volunteer data, a probability map for the pyramidal tract (PYT), and this
      map was applied to patients to calculate DT-derived metrics inside the PYT. In
      CIS patients with clinical symptoms related to motor function, the DT-derived
      mean diffusivity and the lesion volume in the PYT were found to be increased,
      while the fractional anisotropy was no different, when compared to those patients
      without motor symptoms. These results may be explained by several microstructural
      changes in the damaged tissue, such as changes in the permeability of axonal cell
      membranes, decreases of axonal density and edema. The approach taken to analyze a
      specific fiber tract was possible because the axons in the tract have a high
      orientational coherence, allowing tissue structure changes to be isolated from
      the tissue architecture. Its extension to other white matter fiber bundles is
      therefore limited to bundles with high orientational coherence.

PMID- 15862227
TI  - Placing a tool in the spotlight: spatial attention modulates visuomotor responses
      in cortex.
AB  - Visual spatial attention has long been associated with facilitatory effects on
      visual perception. Here, we report that spatial attention can also modulate
      implicit visuomotor processing in dorsal regions of human cortex. Participants
      underwent fMRI scanning while performing a voluntary attentional orienting task
      that varied the category of a task-irrelevant object in the attended location
      (tool vs. non-tool). Data were then analyzed as a function of the attended
      location (left vs. right visual field) and the object category in that location.
      We found that the fMRI BOLD response in two visuomotor-related regions--the
      supplementary motor area (SMA) and the left inferior parietal lobule (IPL)-
      showed an interaction between the location of attention and the location of the
      tool in the bilateral display. Further, these responses were statistically
      distinct from those regions in dorsal cortex showing activity modulated only by
      the tool location or only by the attended location. While the effects of
      attending non-foveally within the visual field have been well documented in
      relation to visual perception, our findings support the proposal that voluntary
      visuospatial attention may also have consequences for the implicit planning of
      object-directed actions.

PMID- 15862228
TI  - Maintaining coherence of dynamic objects requires coordination of neural systems
      extended from anterior frontal to posterior parietal brain cortices.
AB  - Object representation in visual working memory enables humans to perceive a
      consistent visual world and must satisfy two attributes: coherence and dynamic
      updating. The present study measured brain activity using functional magnetic
      resonance imaging (fMRI) during the multiple object permanence tracking (MOPT)
      task, which requires observers to process simultaneously both coherence
      maintenance and dynamic updating of objects. Whole brain analysis revealed
      anterior and ventral parts of frontal area and dorsal frontoparietal activation
      during both object-moving and object-stationary conditions. Subsequent region-of
      interest analyses in the anterior/ventral frontal and the dorsal frontoparietal
      regions revealed that these two systems engage the two different cognitive
      processes involved in the MOPT task, with coherency maintenance processed in the
      anterior/ventral frontal areas and spatial processing in the dorsal
      frontoparietal network. These results suggest that cooperation between these two
      systems underpins object representations in visual working memory.

PMID- 15862229
TI  - Combined event-related fMRI and intracerebral ERP study of an auditory oddball
      task.
AB  - Event-related fMRI (efMRI) has been repeatedly used to seek the neural sources of
      endogenous event-related potentials (ERP). However, significant discrepancies
      exist between the efMRI data and the results of previously published intracranial
      ERP studies of oddball task. To evaluate the capacity of efMRI to define the
      sources of the P3 component of ERP within the human brain, both efMRI and
      intracerebral ERP recordings were performed in eight patients with intractable
      epilepsy (five males and three females) during their preoperative invasive video
      EEG monitoring. An identical auditory oddball task with frequent and target
      stimuli was completed in two sessions. A total of 606 intracerebral sites were
      electrophysiologically investigated by means of depth electrodes. In accordance
      with the finding of multiple intracerebral generators of P3 potential, the target
      stimuli evoked MRI signal increase in multiple brain regions. However, regions
      with evident hemodynamic and electrophysiological responses overlapped only
      partially. P3 generators were always found within hemodynamic-active sites, if
      these sites were investigated by means of depth electrodes. On the other hand,
      unequivocal local sources of P3 potential were apparently also located outside
      the regions with a significant hemodynamic response (typically in mesiotemporal
      regions). Both methods should thus be viewed as mutually complementary in
      investigations of the spatial distribution of cortical and subcortical activation
      during oddball task.

PMID- 15862230
TI  - Imaging speech production using fMRI.
AB  - Human speech is a well-learned, sensorimotor, and ecological behavior ideal for
      the study of neural processes and brain-behavior relations. With the advent of
      modern neuroimaging techniques such as positron emission tomography (PET) and
      functional magnetic resonance imaging (fMRI), the potential for investigating
      neural mechanisms of speech motor control, speech motor disorders, and speech
      motor development has increased. However, a practical issue has limited the
      application of fMRI to issues in spoken language production and other related
      behaviors (singing, swallowing). Producing these behaviors during volume
      acquisition introduces motion-induced signal changes that confound the activation
      signals of interest. A number of approaches, ranging from signal processing to
      using silent or covert speech, have attempted to remove or prevent the effects of
      motion-induced artefact. However, these approaches are flawed for a variety of
      reasons. An alternative approach, that has only recently been applied to study
      single-word production, uses pauses in volume acquisition during the production
      of natural speech motion. Here we present some representative data illustrating
      the problems associated with motion artefacts and some qualitative results
      acquired from subjects producing short sentences and orofacial nonspeech
      movements in the scanner. Using pauses or silent intervals in volume acquisition
      and block designs, results from individual subjects result in robust activation
      without motion-induced signal artefact. This approach is an efficient method for
      studying the neural basis of spoken language production and the effects of speech
      and language disorders using fMRI.

PMID- 15862231
TI  - GLM-beamformer method demonstrates stationary field, alpha ERD and gamma ERS co
      localisation with fMRI BOLD response in visual cortex.
AB  - Recently, we introduced a new 'GLM-beamformer' technique for MEG analysis that
      enables accurate localisation of both phase-locked and non-phase-locked
      neuromagnetic effects, and their representation as statistical parametric maps
      (SPMs). This provides a useful framework for comparison of the full range of MEG
      responses with fMRI BOLD results. This paper reports a 'proof of principle' study
      using a simple visual paradigm (static checkerboard). The five subjects each
      underwent both MEG and fMRI paradigms. We demonstrate, for the first time, the
      presence of a sustained (DC) field in the visual cortex, and its co-localisation
      with the visual BOLD response. The GLM-beamformer analysis method is also used to
      investigate the main non-phase-locked oscillatory effects: an event-related
      desynchronisation (ERD) in the alpha band (8-13 Hz) and an event-related
      synchronisation (ERS) in the gamma band (55-70 Hz). We show, using SPMs and
      virtual electrode traces, the spatio-temporal covariance of these effects with
      the visual BOLD response. Comparisons between MEG and fMRI data sets generally
      focus on the relationship between the BOLD response and the transient evoked
      response. Here, we show that the stationary field and changes in oscillatory
      power are also important contributors to the BOLD response, and should be
      included in future studies on the relationship between neuronal activation and
      the haemodynamic response.

PMID- 15862232
TI  - fMRI temporal clustering analysis in patients with frequent interictal
      epileptiform discharges: comparison with EEG-driven analysis.
AB  - Temporal clustering analysis (TCA) is an exploratory data-driven technique that
      has been proposed for the analysis of resting fMRI to localise epileptiform
      activity without need for simultaneous EEG. Conventionally, fMRI of epileptic
      activity has been limited to those patients with subtle clinical events or
      frequent interictal epileptiform EEG discharges, requiring simultaneous EEG
      recording, from which a linear model is derived to make valid statistical
      inferences from the fMRI data. We sought to evaluate TCA by comparing the results
      with those of EEG correlated fMRI in eight selected cases. Cases were selected
      with clear epileptogenic localisation or lateralisation on the basis of
      concordant EEG and structural MRI findings, in addition to concordant activations
      seen on EEG-derived fMRI analyses. In three, areas of activation were seen with
      TCA but none corresponding to the electro-clinical localisation or activations
      obtained with EEG driven analysis. Temporal clusters were closely coincident with
      times of maximal head motion. We feel this is a serious confound to this approach
      and recommend that interpretation of TCA that does not address motion and
      physiological noise be treated with caution. New techniques to localise
      epileptogenic activity with fMRI alone require validation with an appropriate
      independent measure. In the investigation of interictal epileptiform activity,
      this is best done with simultaneous EEG recording.

PMID- 15862234
TI  - Accuracy and robustness of three-way decomposition applied to NMR data.
AB  - Three-way decomposition is a very versatile analysis tool with applications in a
      variety of protein NMR fields. It has been used to extract structural data from
      3D NOESYs, to determine relaxation rates in large proteins, to identify ligand
      binding in screening for lead compounds, and to complement non-uniformly recorded
      (sparse) spectra. All applications so far concerned experimental data sets; it
      thus remains to address questions of accuracy and robustness of the method using
      simulated data where the correct answer is known. Systematic tests are presented
      for relaxation and NOESY data sets. Mixtures of real and synthetic data are used
      to allow control of various parameters and comparisons with correct reference
      data, while working with input that is as realistic as possible. The influence of
      the following parameters is evaluated: signal-to-noise, overlap of signals and
      the use of a regularization procedure within the algorithm. The main criteria
      used for the evaluation are accuracy and precision. It is shown that
      deterioration of accuracy is indicated by internal checks such as decrease of
      precision. Both with relaxation data and when interpreting NOESY spectra, three
      way decomposition exhibits a robust behavior in situations with severe signal
      overlap and/or poor signal-to-noise, e.g., by avoiding false positives in the NOE
      shapes of NOESY decompositions. As a complement to this study, three-way
      decomposition is compared to other methods that achieve the same type of results.

PMID- 15862233
TI  - Progressive EPR imaging with adaptive projection acquisition.
AB  - Continuous wave electron paramagnetic resonance imaging (EPRI) of living
      biological systems requires rapid acquisition and visualization of free radical
      images. In the commonly used multiple-stage back-projection image reconstruction
      algorithm, the EPR image cannot be reconstructed until a complete set of
      projections is collected. If the data acquisition is incomplete, the previously
      acquired incomplete data set is no longer useful. In this work, a 3-dimensional
      progressive EPRI technique was implemented based on inverse Radon transform in
      which a 3-dimensional EPR image is acquired and reconstructed gradually from low
      resolution to high resolution. An adaptive data acquisition strategy is proposed
      to determine the significance of projections and acquire them in an order from
      the most significant to the least significant. The image acquisition can be
      terminated at any time if further collection of projections does not improve the
      image resolution distinctly, providing flexibility to trade image quality with
      imaging time. The progressive imaging technique was validated using computer
      simulations as well as imaging experiments. The adaptive acquisition uses 50-70%
      less projections as compared to the regular acquisition. In conclusion, adaptive
      data acquisition with progressive image reconstruction should be very useful for
      the accelerated acquisition and visualization of free radical distribution.

PMID- 15862236
TI  - Magnetic resonance in systems with equivalent spin-1/2 nuclides. Part 1.
AB  - Electron paramagnetic resonance (EPR) spectra of S=1/2 systems XL(n) with n
      equivalent nuclei having spin I=1/2 have been simulated for microwave frequencies
      in the L-, X-, and W-bands. It has been shown that for n>2 nuclei, the EPR
      spectra have a more complicated form than anticipated from the usual
      oversimplified analysis, which predicts n+1 lines with intensity ratios given by
      the coefficients of the binomial expansion. For the XL(n) system with n=3, the
      EPR spectra in fact consist of six lines. The exact solution of the spin
      hamiltonian for this case has been obtained, which gives four levels in zero
      magnetic field. For n>2 systems, the degeneracy of the energy levels cannot be
      completely removed by the Zeeman electronic and nuclear interactions. For n>4,
      certain spin states cannot occur, consistent with the (generalized) Pauli
      exclusion principle. Discussion of the underlying theory, invoking exchange
      degeneracy and the appropriate permutation group theory, is included in some
      detail. Analogous considerations hold for NMR spectroscopy of non-radicals.

PMID- 15862235
TI  - Side-chain H and C resonance assignment in protonated/partially deuterated
      proteins using an improved 3D(13)C-detected HCC-TOCSY.
AB  - We propose the use of (13)C-detected 3D HCC-TOCSY experiments for assignment of
      (1)H and (13)C resonances in protonated and partially deuterated proteins. The
      experiments extend 2D C-13-start and C-13-observe TOCSY type experiments proposed
      earlier. Introduction of the third (1)H dimension to 2D TOCSY: (i) reduces the
      peak overlap and (ii) increases the sensitivity per unit time, even for highly
      deuterated (>85%) protein samples, which makes this improved method an attractive
      tool for the side-chain H and C assignment of average sized proteins with natural
      isotope abundance as well as large partially deuterated proteins. The experiments
      are demonstrated with a 16 kDa (15)N, (13)C-labeled non-deuterated apo-CcmE and a
      48 kDa uniformly (15)N, (13)C-labeled and fractionally ( approximately 90%)
      deuterated dimeric sFkpA. It is predicted that this method should be suitable for
      the assignment of methyl (13)C and (1)H chemical shifts of methyl protonated,
      highly deuterated and (13)C-labeled proteins with even higher molecular weight.

PMID- 15862237
TI  - Double-quantum biased covariance spectroscopy: application to the 2D INADEQUATE
      experiment.
AB  - A novel processing scheme is presented that converts a two-dimensional double
      quantum NMR spectrum into a single-quantum correlation spectrum. The covariance
      like spectrum is computed from the 2D Fourier transform spectrum by emphasizing
      contributions that fulfill the double-quantum condition resulting in a symmetric
      spectrum that is easier to analyze. The method is demonstrated for the 2D
      INADEQUATE experiment.

PMID- 15862238
TI  - A modified PGSE for measuring diffusion in the presence of static magnetic field
      gradients.
AB  - With a proper timing of pi pulses, it is possible to reduce the effect of the
      static internal magnetic field gradient on the measurement of diffusion with the
      pulsed gradient spin echo (PGSE). A pulse sequence that in the first order
      eliminates the effect of weak internal static gradients in a standard PGSE
      experiment is introduced. The method should be applied in the cases, where strong
      and short magnetic gradient pulses are used to investigate the motion of liquid
      in heterogeneous samples with large susceptibility differences such as porous
      media.

PMID- 15862239
TI  - Convection-compensating diffusion experiments with phase-sensitive double-quantum
      filtering.
AB  - We present a design scheme for phase-sensitive, convection-compensating diffusion
      experiments with gradient-selected homonuclear double-quantum filtering. The
      scheme consists of three blocks: a 1/2J evolution period during which antiphase
      single-quantum coherences are created; a period of double-quantum evolution; and
      another 1/2J period, during which antiphase single-quantum coherences are
      converted back into an in-phase state. A single coherence transfer pathway is
      selected using an asymmetric set of gradient pulses, and both diffusion
      sensitization and convection compensation are built into the gradient coherence
      transfer pathway selection. Double-quantum filtering can be used either for
      solvent suppression or spectral editing, and we demonstrate examples of both
      applications. The new experiment performs well in the absence of a field
      frequency lock and does not require magnitude Fourier transformation. The
      proposed scheme may offer advantages in diffusion measurements of spectrally
      crowded systems, particularly small molecules solubilized in colloidal solutions
      or bound to macromolecules.

PMID- 15862240
TI  - Some aspects of quantitative 2D NMR.
AB  - We have studied the application of 2D HSQC for quantitative measurements and
      propose some improvements to the previously published Q-HSQC method. Application
      of CPMG-INEPT for polarization transfer period suppresses the evolution of J(HH),
      and thus corrects the shape of the cross-peaks. The better cross-peak shape makes
      phase correction and integration of the cross-peaks easier. Further, the (13)C
      resonance offset dependency can have a significant influence to the results. The
      offset effects can be compensated either by correcting results with a proper
      coefficient, or using 90 degrees composite (13)C pulses in the pulse sequence.
      The results show that these modifications improve the applicability of 2D HSQC
      for quantitative analysis when studying molecules possessing large J(HH)
      couplings and wide (13)C chemical shift range.

PMID- 15862241
TI  - Simultaneous measurement of protein one-bond residual dipolar couplings without
      increased resonance overlap.
AB  - A NMR strategy designed to measure simultaneously and without increased resonance
      overlap scalar and dipolar couplings (RDCs) in (13)C-, (15)N-labeled proteins is
      presented. Contrary to common schemes for simultaneous measurement of RDCs, a
      single reference experiment is used for the extraction of more than one type of
      coupling, thereby reducing the required measurement time. This is accomplished by
      a common reference spectrum followed by a series of interleaved experiments, in
      which a particular coupling dependent parameter is varied according to the
      quantitative J-correlation method or using accordion spectroscopy. To illustrate
      this idea, we have modified the 3D TROSY-HNCO and the 3D CBCA(CO)NH experiment
      allowing efficient measurement of one-bond (1)D(NH), (1)D(C'N),
      (1)D(CalphaHalpha), (1)D(CbetaHbeta), and (1)D(CalphaC') couplings in small to
      medium sized proteins. In addition, the experiments are expected to be useful for
      largely unfolded proteins, which show strong resonance overlap but have very
      favorable relaxation properties. Measurement of RDCs is demonstrated on uniformly
      (15)N-(13)C-labeled ubiquitin and on the sensory domain of the membraneous two
      component fumarate sensor DcuS of Escherichia coli (17 kDa). DcuS was found to be
      unstable and to precipitate in one to two weeks. RDCs obtained from these
      experiments are in good agreement with the 1.8A X-ray structure of ubiquitin.

PMID- 15862242
TI  - Theoretical and experimental investigation of (13)C relayed (2)H-(2)H-COSY 2D
      experiments: application to the analysis of weakly aligned solutes.
AB  - We describe new NMR 2D experiments denoted DECADENCY for DEuterium CArbon
      DEuterium Nuclear Correlation spectroscopY dedicated to the analysis of
      anisotropic deuterium spectra. They belong to the class of X-relayed Y,Y-COSY 2D
      experiments that was initially explored in the case of a (1)H-X-(1)H fragment
      (I(X)=1/2) in isotropic medium. DECADENCY 2D experiments permit to correlate the
      quadrupolar doublets associated with two inequivalent deuterium nuclei in an
      oriented CD(2) fragment through heteronuclear polarization transfers. Two kinds
      of pulse sequences are described here using either a double INEPT-type or DEPT
      type process. DECADENCY 2D experiments provide an interesting alternative to (2)H
      (2)H COSY experiments when the geminal (2)H-(2)H total coupling (scalar and
      dipolar) is null or too small to provide visible cross-correlation peaks. Such a
      situation is typically observed for geminal deuteriums in prochiral or chiral
      molecules dissolved in chiral liquid crystals. The efficiency of these techniques
      is illustrated using dideuterated prochiral molecules, the
      phenyl[(2)H(2)]methanol and the 1-chloro[1-(2)H(2)]nonane, both dissolved in
      organic solutions of poly-gamma-benzyl-l-glutamate. The advantages of each
      sequence are presented and discussed. It is shown that the relative sign of the
      quadrupolar doublets can be determined.

PMID- 15862243
TI  - A variable temperature EPR study of Mn(2+)-doped NH(4)Cl(0.9)I(0.1) single
      crystal at 170 GHz: zero-field splitting parameter and its absolute sign.
AB  - EPR measurements have been carried out on a single crystal of Mn(2+)-doped
      NH(4)Cl(0.9)I(0.1) at 170-GHz in the temperature range of 312-4.2K. The spectra
      have been analyzed (i) to estimate the spin-Hamiltonian parameters; (ii) to study
      the temperature variation of the zero-field splitting (ZFS) parameter; (iii) to
      confirm the negative absolute sign of the ZFS parameter unequivocally from the
      temperature-dependent relative intensities of hyperfine sextets at temperatures
      below 10K; and (iv) to detect the occurrence of a structural phase transition at
      4.35K from the change in the structure of the EPR lines with temperature below
      10K.

PMID- 15862244
TI  - Triple-quantum-filtered imaging of sodium in presence of B(0) inhomogeneities.
AB  - Triple quantum filtered sodium MRI techniques have been recently demonstrated in
      vivo. These techniques have been previously advocated as a means to separate the
      sodium NMR signal from different physiological compartments based on the
      differences between their relaxation rates. Among the different triple quantum
      coherence transfer filters, the three-pulse coherence transfer filter has been
      demonstrated to be better suited for human imaging than the traditional four
      pulse implementation. While the three-pulse structure has distinct advantages in
      terms of RF efficiency, the lack of a refocusing pulse in the filter introduces
      an increased dependence on the main magnetic field inhomogeneities, which can
      sometimes lead to significant signal loss. In this paper, we characterize these
      dependencies and introduce a method for their compensation through the
      acquisition of a B(0) map and the use of a modified phase cycling scheme.

PMID- 15862246
TI  - Efficient compensation of low-frequency magnetic field disturbances in NMR with
      fluxgate sensors.
AB  - A simple stabilization scheme of B(0) magnetic field fluctuations is described.
      The method is based on external measurements of time dependent magnetic field
      fluctuations by fluxgate sensors and generation of a compensating correction
      current in a coil mounted directly on an NMR magnet. It is shown that such an
      approach efficiently eliminates relatively slow magnetic field variations with
      frequency up to approximately 100 Hz. In combination with a standard (2)H field
      frequency lock system, the method enables acquisition of reproducible lineshapes
      and dramatically improves overall performance of a high resolution NMR
      spectrometer. The presented solution might substitute for the internal lock
      system in these case where deuterium lock is not available.

PMID- 15862245
TI  - Image artifacts in very low magnetic field MRI: the role of concomitant
      gradients.
AB  - While MRI at very low magnetic fields has certain potential advantages, it may
      also face problems that are not typical for MRI at conventional and high field
      (0.1-10T). Major differences arise due to the presence of concomitant components
      of inhomogeneous magnetic field (gradients) that are transverse to the major B(z)
      field, B(0). These concomitant transverse field components are inevitably
      generated by the same gradient coils that generate desired B(z) imaging gradients
      as routinely used in MRI for spatial encoding. In the hypothetical case (linear
      spatial variation of B(z) field amplitude due to the imaging gradients, no
      concomitant transverse field components, no B(0) and B(1) field inhomogeneities,
      etc.), Fourier transform MRI preserves the shape of the real object being
      examined. It is demonstrated herein that unavoidable concomitant transverse field
      gradients, G, result in an image deformation of the object's actual shape by
      bending straight lines and planes with a characteristic curvature radius
      R(c)=B(0)/G. For imaging gradients on the order of 10 mT/m and B(0) of 1T, the
      radius R(c) is about 100 m and image distortions are generally negligible.
      However, for B(0) of 1 mT, R(c) is 10 cm, which is less than a typical FOV in
      human studies. This manuscript derives expressions describing geometrical
      relationships between the imaged object and the obtained MR data. In addition to
      geometrical distortions, image intensity will be modulated in a complex,
      spatially dependent manner. Hence, if unaccounted for, corresponding image
      distortions-geometry and intensity-will create substantial difficulties in very
      low field image interpretation.

PMID- 15862247
TI  - Electromagnetic characterization of rectangular ferroelectric resonators.
AB  - An optimized geometry for a rectangular ferroelectric resonator (FR) is proposed
      to increase signal-to-noise ratio in EPR spectroscopy. To develop optimization
      criteria, the distribution of the microwave electromagnetic field in the FR is
      computed and analyzed. The computations, based on solution of Maxwell's field
      equations, were made for two types of rectangular FRs-a FR with a hollow sample
      hole and a FR with a blind sample hole. To introduce the samples, a hole was
      drilled through the resonator with its axis aligned to the axis of the FR. We
      computed and studied the spatial distributions of H- and E-components of the
      microwave electromagnetic field for two rectangular FRs, made of single-crystal
      potassium tantalate, with the following sizes: 1.9 x 1.9 x 1.4mm(3) and 1.7 x 1.7
      x 3.1mm(3). As analysis of the obtained data indicated, in both resonators, the
      lowest mode was TE(11delta). By analyzing the distribution of the microwave field
      in the FR and comparing it with the experimental result, we developed
      optimization criteria for the geometry of a rectangular FR.

PMID- 15862248
TI  - Correlating fast and slow chemical shift spinning sideband patterns in solid
      state NMR.
AB  - An experiment is presented that enables the measurement of small chemical shift
      anisotropy tensors under fast magic-angle spinning (MAS). The two-dimensional
      spectra obtained give a fast MAS sideband pattern in the directly observed
      dimension with the spinning sideband intensities equivalent to the chemical shift
      anisotropy scaled by a factor of N, or equivalently the sample spinning frequency
      scaled by 1/N, in the indirectly observed dimension. The scaling factor may be
      arbitrarily varied by changing the number and timings of the rotor synchronized
      pi-pulses used. Desirable features of the experiment include a fixed length pulse
      sequence and efficient sampling of the indirectly observed dimension. In
      addition, neither quadrature detection in the indirect dimension nor storage
      periods are required, consequently no signal intensity is discarded by the pulse
      sequence. The experiment is demonstrated using (31)P NMR of sodium phosphate and
      (13)C NMR of fumaric acid monoethyl ester for which a scaling factor of N=10.2
      was employed.

PMID- 15862249
TI  - Enhancement of efficiency in photo-excitation to the triplet state by laser-pulse
      reshaping.
AB  - An optical system is proposed to enhance efficiency in photo-excitation to the
      triplet state by reshaping an original laser pulse into a train of pulses. This
      optical system can be used to improve the attainable nuclear spin polarization in
      dynamic nuclear polarization experiments using photo-excited triplet electron
      spins.

PMID- 15862250
TI  - Assigning uncertainties in the inversion of NMR relaxation data.
AB  - Recovering the relaxation-time density function (or distribution) from NMR decay
      records requires inverting a Laplace transform based on noisy data, an ill-posed
      inverse problem. An important objective in the face of the consequent ambiguity
      in the solutions is to establish what reliable information is contained in the
      measurements. To this end we describe how upper and lower bounds on linear
      functionals of the density function, and ratios of linear functionals, can be
      calculated using optimization theory. Those bounded quantities cover most of
      those commonly used in the geophysical NMR, such as porosity, T(2) log-mean, and
      bound fluid volume fraction, and include averages over any finite interval of the
      density function itself. In the theory presented statistical considerations enter
      to account for the presence of significant noise in the signal, but not in a
      prior characterization of density models. Our characterization of the
      uncertainties is conservative and informative; it will have wide application in
      geophysical NMR and elsewhere.

PMID- 15862251
TI  - Correspondence between spin-dynamic phases and pulse program phases of NMR
      spectrometers.
AB  - Spin state selective experiments have become very useful tools in solution NMR
      spectroscopy, particularly in the context of TROSY line narrowing. However, the
      practical implementation of such pulse sequences is frequently complicated by
      unexpected instrument behavior. Furthermore, a literal theoretical analysis of
      sequences published with specific phase settings can fail to rationalize such
      experiments and can seemingly contradict experimental findings. In this
      communication, we develop a practical approach to this ostensible paradox. Spin
      dynamic design, rationalization, and simulation of NMR pulse sequences, as well
      as their confident and reliable implementation across current spectrometer
      hardware platforms, require precise understanding of the underlying nutation axis
      conventions. While currently often approached empirically, we demonstrate with a
      simple but general pulse program how to uncover these correspondences a priori in
      the general case. From this, we deduce a correspondence table between the spin
      dynamic phases used in NMR theory and simulation on the one hand and pulse
      program phases of current commercial spectrometers on the other. As a practical
      application of these results, we analyze implementations of the original (1)H
      (15)N TROSY experiment and illustrate how steady-state magnetization can be
      predictably, rather than empirically, added to a desired component. We show why
      and under which circumstances a literal adoption of phases from published
      sequences can lead to incorrect results. We suggest that pulse sequences should
      be consistently given with spin-dynamically correct (physical) phases, rather
      than in spectrometer-specific (software) syntax.

PMID- 15862252
TI  - Optimal electric fields for different sample shapes in high resolution NMR
      spectroscopy.
AB  - For many applications, reducing sample resistance, rather than increasing probe Q
      or filling factor, is the only way to further improve the signal-to-noise ratio
      of cryogenically cooled NMR probes. In this paper, bounds are calculated for the
      minimum sample resistance that can be achieved for various sample geometries. The
      sample resistance of 100 mM NaCl in H(2)O in 5 mm sample tubes was measured on a
      600 MHz cold probe to be within 14% of the optimum value. The minimum sample
      resistance can however be lowered by altering the tube cross section. Rectangular
      tubes oriented with the long axis along the RF magnetic field are particularly
      favourable.

PMID- 15862253
TI  - Linking NMR pulse sequences: derivative relation between the responses of two
      pulse sequences.
AB  - Examples are shown of how the derivative of the response of an NMR pulse sequence
      with respect to a variable in that pulse sequence can be obtained by another
      pulse sequence. This approach holds the potential of being a tool for discovery
      of new pulse sequences or a means of understanding how some pulse sequences are
      related to each other.

PMID- 15862254
TI  - Stray field measurements of flow displacement distributions without pulsed field
      gradients.
AB  - The probability distribution P(zeta) of diffusive and advective molecular
      displacements is determined using a fixed field gradient (FFG) pulse sequence, on
      fluid flow through a Bentheimer sandstone, in the grossly inhomogeneous stray
      field of a super-conducting magnet. Two decades of q-space are scanned with
      stimulated echoes, using the gradient of the stray field and variable encoding
      times delta. The strength of the gradient permits the use of short encoding
      times, which is desirable for limiting the distorting effects produced by flow
      displacements through susceptibility induced field inhomogeneities. CPMG and CP
      echo trains are used to refocus separately the real and imaginary parts of the
      stimulated echo, for experimental efficiency.

PMID- 15862255
TI  - Physician competency? Teaching old dogs new tricks.

PMID- 15862256
TI  - Laparoscopic antireflux surgery provides excellent results and quality of life in
      gastroesophageal reflux disease patients with respiratory symptoms.
AB  - Medical and surgical treatment are able to improve symptoms in patients with
      gastroesophageal reflux disease (GERD). The aim of this study was to evaluate the
      outcome following laparoscopic antireflux surgery in GERD patients with primary
      respiratory-related symptoms and to investigate the quality of life index before
      and after therapy. Three hundred thirty-eight consecutive patients underwent
      surgical treatment for GERD-induced symptoms. Of this group 126 patients had
      primary respiratory symptoms related to GERD. All patients were studied by means
      of a symptom questionnaire, endoscopy, esophageal manometry, 24-hour esophageal
      pH monitoring, and a barium esophagogram. In addition, the quality of life was
      measured by the means of the Gastrointestinal Quality of Life Index (GIQLI). All
      patients had medical therapy with proton pump inhibitors preoperatively. A
      laparoscopic fundoplication was performed in all patients. The outcome was
      assessed 3 and 12 months postoperatively. Following surgery, all respiratory
      symptoms were significantly improved. While GIQLI was highly impaired before
      surgical therapy, a significant improvement of quality of life was obtained.
      Because medical treatment is likely to fail in GERD patients with respiratory
      symptoms, the need for surgery arises and may be the only successful treatment in
      the long term. Quality of life was significantly improved by surgical treatment.

PMID- 15862258
TI  - Right portal vein thrombosis after splenectomy for trauma.
AB  - Portal vein thrombosis may complicate splenectomy in patients with hemolytic
      anemia and myeloproliferative disease, whereas the frequency of portal vein
      thrombosis in case of trauma is not defined. A case of right portal vein
      thrombosis after splenectomy for trauma is reported in this paper. Hematologic
      workup did not reveal an underlying platelet or coagulation disorder. The patient
      was promptly anti-coagulated with complete recanalization of the portal vein. We
      conclude that mild symptoms, like abdominal pain and fever, after splenectomy
      should be investigated with a color Doppler ultrasonography to confirm or rule
      out a diagnosis of portal thrombosis and to anti-coagulate the patient with
      thrombosis, thus preventing bowel infarction and secondary portal hypertension.
      Routine postoperative color Doppler might also be justified in all
      postsplenectomy patients (without hematologic diseases) for early detection of a
      portal vein thrombosis.

PMID- 15862257
TI  - Hepatitis status, child-pugh classification, and serum AFP levels predict
      survival in patients treated with transarterial embolization for unresectable
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) represents one of the most prevalent cancers
      worldwide. Most patients are not surgical candidates, and transarterial
      embolization (TAE) has been used to treat patients with unresectable HCC. The
      purpose of this study was to identify factors that predict survival in patients
      treated with TAE at a Western medical center. Review of a prospective database
      identified 345 patients treated for HCC at University Hospital (Newark, NJ)
      between July 1998 and July 2004. Of these patients, 109 patients underwent TAE.
      Eleven of these patients were subsequently treated surgically and excluded from
      this study. Of the remaining 98 patients, demographic data and laboratory values
      were analyzed to predict survival by univariate and multivariate analysis.
      Several factors, including hepatitis status, Child-Pugh classification, serum
      alpha fetoprotein levels <500 ng/ml, bilirubin <2.0 mg/dl, prothrombin time <16
      seconds, platelet count <200 x 10(9)/l, albumin >3.5 gm/dl, and multiple
      treatments, predicted survival by univariate analysis. Serum alpha fetoprotein
      levels, Child-Pugh classification, and hepatitis status were found by
      multivariate analysis to independently predict survival. These factors may help
      to select patients with unresectable HCC who might benefit from TAE.

PMID- 15862259
TI  - Radiofrequency ablation for hypersplenism in patients with liver cirrhosis: a
      pilot study.
AB  - Radiofrequency ablation is a relatively new technique used for local ablation of
      unresectable tumors. We investigated the feasibility and efficacy of
      radiofrequency ablation for hypersplenism and its effect on liver function in
      patients with liver cirrhosis and portal hypertension. Nine consecutive patients
      with hypersplenism due to cirrhotic portal hypertension underwent radiofrequency
      ablation in enlarged spleens. The ablation was performed either intraoperatively
      or percutaneously. Patients are followed up for over 12 months. After treatment,
      between 20% and 43% of spleen volume was ablated, and spleen volume increased by
      4%-10.2%. White blood cell count, platelet count, liver function, and hepatic
      artery blood flow showed significant improvement after 1-year follow-up. Splenic
      vein and portal vein blood flow were significantly reduced. Only minor
      complications including hydrothorax (three of nine patients) and mild abdominal
      pain (four of nine patients) were observed. No mortality or other morbidity
      occurred. Radiofrequency ablation is a safe, effective, and minimally invasive
      approach for the management of splenomegaly and hypersplenism in patients with
      liver cirrhosis and portal hypertension. Increased hepatic artery blood flow may
      be responsible for sustained improvement of liver condition. Radiofrequency
      ablation may be used as a bridging therapy for cirrhotic patients waiting for
      liver transplantation.

PMID- 15862260
TI  - Intermittent hepatic vein--total vascular exclusion during liver resection:
      anatomic and clinical studies.
AB  - Bleeding from hepatic veins remains a problem during liver surgery. Perceived
      difficulties in the dissection and isolation of these retrohepatic venous
      structures have limited the widespread use of hepatic vein control during liver
      resection. The purpose of this study was to delineate the anatomy of the hepatic
      veins and to apply this knowledge to a series of patients undergoing liver
      resection with intermittent hepatic vein-total vascular exclusion (IHV-TVE). A
      detailed description of the hepatic venous anatomy was formulated using 20
      cadaveric dissections in conjunction with anatomic descriptions during 30
      hepatectomies. With the benefit of improved anatomic knowledge, we evaluated a
      series of 45 consecutive major liver resections in which hepatic veins were
      isolated and the technique of IHV-TVE was applied. The hepatocaval ligament must
      be divided to isolate the right hepatic vein. It was closely associated with a
      caudate vein 69% of the time. The hepatic veins were isolated in 45 consecutive
      patients who underwent a major hepatic resection. The portal triad and the
      hepatic veins were occluded intermittently (20 minutes with 5 minutes of
      reperfusion) with Rommel tourniquets. Mean total warm ischemic time was 65 +/-
      24.5 minutes. Mean estimated blood loss was 864 +/- 514 ml. Eighteen percent of
      patients required blood transfusions. Complications were identified in 16
      patients (35.5%), and the average length of hospital stay was 10.5 +/- 3.4 days.
      There were no deaths. Detailed anatomic knowledge of the hepatocaval ligament and
      the hepatic veins allows for safe extrahepatic control of the hepatic veins
      during major hepatic surgery. The technique was well tolerated and may have
      limited intraoperative blood loss.

PMID- 15862261
TI  - Is routine placement of surgical drains necessary after elective hepatectomy?
      Results from a single institution.
AB  - Routine drainage is no longer used after many major abdominal procedures.
      However, the role of routine surgical drainage after hepatic resection is
      unclear. Of the two randomized trials published, one concluded drainage is
      unnecessary after hepatectomy, and another concluded it could be used after major
      resections only. Between January 1999 and December 2003, 211 elective hepatic
      resections were performed by two surgeons at Auckland Hospital. Drains were used
      routinely by one surgeon (n = 126), while another routinely did not drain (n =
      85). Patients undergoing a biliary reconstruction were not included in this
      analysis. Patient and clinical data were recorded prospectively, and no outcome
      analyses were performed until 2004. The demographic features were similar between
      the drained and non-drained groups. There were no differences in length of
      hospital stay (no drain, 7 +/- 0.8 days; drain, 7 +/- 0.9 days: P = not
      significant [NS]), in mortality (no drain, 1.2%; drain, 1.6%: P = NS), biliary
      fistula (no drain, zero cases; drain, two cases: P = NS), or overall complication
      rate (no drain, 50.5%; drain, 54.7%: P = NS). Both groups had similar rates of
      postoperative collection (no drain, four patients [5%]; drain, five patients
      [4%]: P = NS), and there was no difference in the use of percutaneous drainage of
      collections between the groups (no drain, four patients [5%]; drain, two patients
      [2%]: P = NS). Multivariate analysis showed that intraoperative blood loss of
      2000 ml or greater (relative risk [RR], 1.57; 95% confidence interval [CI], 1.39
      1.75; P < 0.01), number of segments resected (RR, 1.4; 95% CI, 1.21-1.89; P <
      0.01), and presence of steatosis/fibrosis or cirrhosis (RR, 1.6; 95% CI, 1.01
      2.1; P < 0.05) to be predictive of postoperative complications. The presence of a
      surgical drain was not predictive of complications. Routine surgical drainage
      after elective hepatectomy is not necessary.

PMID- 15862262
TI  - Impact of aberrant arterial anatomy and location of anastomosis on technical
      outcomes after liver transplantation.
AB  - Variations in donor and recipient arterial anatomy frequently present challenges
      for surgeons when attempting to establish proper arterial inflow during liver
      transplantation. We reviewed our data on 233 adult primary liver transplants,
      conducted from January 1996 through December 2001, to determine the impact of
      these variations on the outcomes after liver transplantation. Twenty-four (10.3%)
      arterial complications were encountered at a mean of 2.27 months after
      transplant. Carrel patches for the anastomoses were not used in 33 patients
      (14%), which had no relation to arterial complications (P = 0.7). Sixty-one
      donors (26.2%) had at least one aberrant artery, which had no relation to
      arterial complications. However, use of donor celiac artery for anastomosis was
      significantly associated with higher arterial complications (16% versus other
      choices, P = 0.03). Furthermore, use of common hepatic recipient artery was
      associated with higher arterial complications (16%, P = 0.03). There were 58
      total biliary complications (24.8%). Biliary complications were associated with
      the presence of arterial complications (P = 0.01). In conclusion, aberrant donor
      arterial anatomy was not associated with an increased rate of arterial
      complications; however, choice of location of arterial anastomosis may be a
      significant factor. Biliary complications were associated with arterial
      complications.

PMID- 15862263
TI  - Postoperative severe microangiopathic hemolytic anemia associated with a giant
      hepatic cavernous hemangioma.
AB  - Complications related to liver hemangioma are rare. We herein describe the case
      of a patient with three giant cavernous hemangiomas of the liver, of which two
      were resected for symptoms. A significant microangiopathic hemolytic anemia
      occurred in the early postoperative period, leading to acute renal failure and
      necessitating blood transfusions. The systematic evaluation of hemolytic
      processes in the postoperative patient is described. Surgeons should be aware of
      the potential for hemolytic complications after major surgery when giant hepatic
      hemangiomas are present.

PMID- 15862264
TI  - Mirizzi syndrome and gallstone ileus: an unusual presentation of gallstone
      disease.
AB  - We discuss the case of a man with an unusual complication of gallstone disease.
      An 85-year-old patient presented to the emergency department with a 3-week
      history of abdominal pain in the right upper abdominal quadrant. Thoracoabdominal
      radiography demonstrated that the whole extrahepatic biliary tree, including the
      common bile duct, common hepatic duct, gallbladder, and left and right hepatic
      ducts, were visibly delineated by air. The operative findings revealed a small
      shrunken gallbladder, a fistula between the gallbladder fundus and the gastric
      antrum, and a cholecystohepatic fistula, corresponding to Mirizzi syndrome, type
      II. A large gallstone was found impacted in the jejunum. This patient seems to
      have developed initially a cholecystohepatic fistula. Due to the acute
      inflammatory process, the stone eroded through the gallbladder wall and into the
      gastric antrum, passing from the antrum into the small bowel, where it became
      impacted. We suggest that the natural history of Mirizzi syndrome does not end
      with a cholecystobiliary fistula but that the continuous inflammation in the
      triangle of Calot may result in a complex fistula involving not only the biliary
      tract but also the adjacent viscera.

PMID- 15862265
TI  - Computed tomography diagnosis of ischemia and complete obstruction in small bowel
      obstruction: a systematic review.
AB  - This review was designed to describe the diagnostic performance of computed
      tomography (CT) in assessing bowel ischemia and complete obstruction in small
      bowel obstruction (SBO). A MEDLINE search (1966-2004) identified 15 studies
      dealing with the CT diagnosis of ischemia and complete obstruction in SBO.
      Ischemia was defined by operative findings, and complete obstruction was defined
      by enteroclysis or operative findings. Aggregated sensitivity, specificity, and
      positive and negative predictive values (PPV and NPV) were calculated. Eleven of
      15 studies reported on the CT diagnosis of ischemia in SBO based on 743 patients.
      The aggregated performance characteristics of CT for ischemia in SBO were
      sensitivity of 83% (range, 63-100%), specificity of 92% (range, 61-100%), PPV of
      79% (range, 69-100%), and NPV of 93% (range, 33.3-100%). Seven of 15 studies
      evaluated the CT classification of complete obstruction based on 408 patients.
      The aggregated performance characteristics of CT for complete obstruction were
      sensitivity of 92% (range, 81-100%), specificity of 93% (range, 68-100%), PPV of
      91% (range, 84-100%), and NPV of 93% (range, 76-100%). This review demonstrates
      the high sensitivity of CT for ischemia in the setting of SBO and suggests that a
      CT scan finding of partial SBO is likely to reflect a clinical condition that
      will resolve without surgical intervention.

PMID- 15862266
TI  - Adenocarcinoma after ileoanal anastomosis for familial adenomatous polyposis:
      review of risk factors and current surveillance apropos of a case.
AB  - Restorative proctocolectomy has become the most common surgical option for
      familial adenomatous polyposis (FAP) patients, based on the premise that it
      provides good functional results and reduces colorectal cancer risk. But several
      adenomas may develop in the pouch mucosa over the years, and even cancer at the
      anastomosis or in the pouch mucosa has been reported rarely. This article aims to
      describe a case of pouch cancer after restorative proctocolectomy for FAP,
      reviewing the possible causes of this unfortunate outcome. A 40-year-old man
      started presenting with fecal blood loss 12 years after restorative
      proctocolectomy with mucosectomy and hand-sewn anastomosis for FAP. Proctologic
      examination revealed an elevated mass 3 cm from the anal margin, which biopsy
      determined to be a mucinous adenocarcinoma. The patient underwent pouch excision
      and terminal ileostomy. Histologic analysis showed a 2.2 cm mucinous
      adenocarcinoma between the ileal and anal mucosa (T2N0Mx) and multiple tubular
      microadenomas in the ileal pouch. The present case and the data presented here
      suggest that restorative proctocolectomy is not a "cancer-free" alternative to
      ileorectal anastomosis, because it does not remove the risk of metachronous
      intestinal neoplasia. Although the long-term risk of malignancy is not known,
      lifelong follow-up seems to be necessary after restorative proctocolectomy.
      Current recommendations for pouch surveillance are presented.

PMID- 15862267
TI  - Selective inhibition of endothelin receptor A as an anti-angiogenic and anti
      proliferative strategy for human pancreatic cancer.
AB  - Endothelin-1 (ET-1) plays a major role in tumor proliferation and angiogenesis of
      various types of cancer acting through endothelin receptors A and B (ET(R)A and
      ET(R)B). The aim of this study was to analyze the ET-1/ET(R) system in human
      pancreatic cancer cell lines and to evaluate the effect of a selective endothelin
      A inhibitor in vitro and in vivo in an orthotopic mouse model. Three different
      human pancreatic cancer cell lines, MiaPaCa-2, AsPC-1, and Panc-1, were studied.
      We found that proliferation of human pancreatic carcinoma cells expressing ET(R)A
      was significantly reduced with a selective antagonist. Hypoxic conditions led to
      improved results compared to a normoxic environment (MiaPaCa-2: -53% vs. -18%;
      AsPC-1: -54% vs. -46%). Proliferation of ET(R)A negative Panc-1 cells was not
      decreased. In vivo, the selective ET(R)A inhibition resulted in reduced
      angiogenesis as measured by lower microvessel densities (MiaPaCa-2: -47%; AsPC-1:
      -55%). The blockade of ET(R)A decreased the volume (MiaPaCa-2: -87%; AsPC-1: 
      28%) and metastatic spread (MiaPaCa-2: -95.5%; AsPC-1: -27%) of receptor-positive
      tumors, thereby increasing survival in experimental pancreatic cancer. ET(R)A
      blockade did not show an effect on ET(R)A negative Panc-1 tumors. Therefore,
      targeting ET(R)A with a selective antagonist might provide a new approach to
      reducing proliferation and angiogenesis in human pancreatic cancer.

PMID- 15862268
TI  - Surgical treatment of pancreas divisum causing chronic pancreatitis: the outcome
      benefits of duodenum-preserving pancreatic head resection.
AB  - Pancreas divisum (PD) represents a duct anomaly in the pancreatic head ducts,
      leading frequently leading to recurrent acute pancreatitis (rAP) or chronic
      pancreatitis (CP). Based on endoscopic retrograde cholangiopancreatography,
      pancreas divisum can be found in 1% to 6% of patients with pancreatitis. The
      correlation of this abnormality with pancreatic disease is an issue of continuing
      controversy. Because of the underlying duct anomalies and major
      pathomorphological changes in the pancreatic head, duodenum-preserving pancreatic
      head resection (DPPHR) offers an option for causal treatment. Thirty-six patients
      with pancreatitis caused by PD were treated surgically. Thirty patients suffered
      from CP, 6 from rAP. The mean duration of the disease was 47.5 and 49.8 months,
      respectively. The age at the time of surgery was 39.2 years in the CP group, and
      27.6 years in the rAP group. Median hospitalization since diagnosis was 18.8
      weeks for CP patients and 24.6 weeks for rAP patients. Previous procedures
      performed in these patients included endoscopic papillotomy (30%), duct stenting
      (14%), and surgical treatment (17%). The median preoperative pain score was 8 on
      a visual analog scale. According to the classification of pancreas divisum, 10
      patients demonstrated a complete PD, 25 had a functionally incomplete PD, and 1
      had a dorsal duct type. The pain status as well as the endocrine (oral glucose
      tolerance test) and exocrine (pancreolauryl test) function were evaluated
      preoperatively and early and late postoperatively with a median follow-up time of
      39.3 months. There was no operative-related mortality. The follow-up was 100%; 4
      patients died (1 from suicide, 1 from cardiac arrest, and 2 from cancer of the
      esophagus). Fifty percent of the patients were completely pain-free, 31% had a
      significant reduction of pain with a median pain score of 2 (P < 0.001). Six
      patients (5 CP, 1 rAP) had further attacks of acute pancreatitis with a need for
      hospitalization. DPPHR reduced pain and preserved the endocrine function in the
      majority of patients with pancreas divisum. Therefore, DPPHR is an alternative to
      other resective or drainage procedures after failure of interventional treatment.

PMID- 15862269
TI  - Transphrenic fistulization of a subphrenic abscess to lung parenchyma.
AB  - A 53-year-old woman was admitted with respiratory distress. For several years,
      she had chronic alcoholic pancreatitis with ductal stones that were treated with
      a stent and with shockwave lithotripsy. Both treatments were unsuccessful, and
      the pancreatitis was complicated with an infected pseudocyst. The pancreatic head
      had to be resected, which was complicated with recurrent subphrenic abscesses.
      She then was admitted with respiratory distress and initially diagnosed with
      pneumonia of the right lower lobe. Further investigations showed
      supradiaphragmatic and subdiaphragmatic air-fluid levels. In both collections
      Streptococcus milleri was cultured, and subsequently the patient was diagnosed
      with a fistula connecting the subdiaphragmatic abscess with pulmonary tissue.
      This was treated with intravenous amoxicillin/clavulanate and drainage of the
      subdiaphragmatic collection. She did not develop a pulmonary empyema, because
      multiple adhesions, which were due to recurrent abscesses after pancreatic
      surgery, prevented breakthrough into the pleural cavity.

PMID- 15862270
TI  - Survival after gastric adenocarcinoma resection: eighteen-year experience at a
      single institution.
AB  - Gastric adenocarcinoma is the second leading cause of cancer death worldwide. In
      Western series, survival rates vary widely and are generally lower than those
      reported from Eastern series. We performed a retrospective analysis of cases
      operated on at the Johns Hopkins Hospital over the past 18 years and collected
      data on demographics, tumor characteristics, pathologic stage, treatment methods,
      complications, survival time, and other relevant factors. Survival according to
      stage of disease, Lauren tumor type, tumor location, time period, and
      administration of adjuvant therapy was analyzed, and results were compared with
      those of other Western series. During this period, 436 patients with gastric
      adenocarcinoma underwent resection. We have shown a statistically significant
      association between survival and margin status, stage of disease, and Lauren
      tumor type. Overall 5-year survival was 26%, and 5-year survival after R0
      resection was 33%. No significant difference was detected between survival and
      tumor location, time period of treatment, or administration of adjuvant therapy.
      Analysis of various Western series reveals major differences between the cohorts
      under study, such as stage of disease, extent of resection, tumor type, and tumor
      location. Many of the reported differences among Western series may be due to
      cohort differences, such as stage of disease, extent of resection, tumor type,
      and tumor location.

PMID- 15862271
TI  - Identification and management of an errant antiperistaltic Roux limb after total
      gastrectomy.
AB  - We recently evaluated two patients because of persistent, unexplained bilious
      vomiting following total gastrectomy with Roux-en-Y esophagojejunostomy. With the
      aid of intestinal manometry and reoperation, an antiperistaltic Roux limb was
      discovered in both cases. Isoperistaltic repositioning of the Roux limb led to
      resolution of both patients' symptoms. These case reports illustrate the
      devastating consequences of a poorly constructed Roux-en-Y esophagojejunostomy
      and demonstrate the utility of intestinal manometry in aiding the diagnosis of
      problems related to the Roux limb, particularly when surgical reexploration is
      not preferred or is inconclusive. By highlighting this avoidable technical error,
      we hope to prevent its future occurrence.

PMID- 15862272
TI  - Laparoscopic spleen-preserving distal pancreatectomy.
AB  - Distal pancreatectomy with spleen preservation may be the preferred procedure for
      certain benign tumors and cystic lesions of the pancreatic body or tail.
      Alternatively, laparoscopic removal including either distal pancreatectomy with
      splenectomy or splenic-preservation with ligation of the splenic vessels have
      also been described. We describe, herein, our method to perform spleen-preserving
      laparoscopic distal pancreatectomy that preserves the splenic vessels and hence
      splenic function. The described technique of spleen-preserving distal
      pancreatectomy has been used in two patients with favorable results. Both
      patients underwent laparoscopic distal pancreatectomy with splenic conservation
      for an oligocystic serous cystadenoma and serous cystadenoma. Operative time was
      3-6 hours with total blood loss of less than 200 cc in both cases. The length of
      stay in the hospital was 4-8 days and both patients returned to work within 3
      weeks. Laparoscopic spleen-preserving distal pancreatectomy should be considered
      for younger patients with select body or tail lesions that are not candidates for
      less extensive procedures.

PMID- 15862274
TI  - Rectal impaction with epoxy resin: a case report.
AB  - We describe a unique case of a patient presenting with rectal impaction following
      self-administration of a liquid used as masonry adhesive for anal sexual
      gratification. The solidified matter required laparotomy for its removal.
      Strategies for removing rectal foreign bodies are discussed as well as other
      consequences of inserting foreign material per rectum.

PMID- 15862275
TI  - Synergistic heterozygosity in mice with inherited enzyme deficiencies of
      mitochondrial fatty acid beta-oxidation.
AB  - We have used mice with inborn errors of mitochondrial fatty acid beta-oxidation
      to test the concept of synergistic heterozygosity. We postulated that clinical
      disease can result from heterozygous mutations in more than one gene in single or
      related metabolic pathways. Mice with combinations of mutations in mitochondrial
      fatty acid beta-oxidation genes were cold challenged to test their ability to
      maintain normal body temperature, a sensitive indicator of overall beta-oxidation
      function. This included mice of the following genotypes: triple heterozygosity
      for mutations in very-long-chain acyl CoA dehydrogenase, long-chain acyl CoA
      dehydrogenase, and short-chain acyl CoA dehydrogenase genes (VLCAD+/-//LCAD+/
      //SCAD+/-); double heterozygosity for mutations in VLCAD and LCAD genes (VLCAD+/
      //LCAD+/-); double heterozygosity for mutations in LCAD and SCAD genes (LCAD+/
      //SCAD+/-); single heterozygous mice (VLCAD+/-, LCAD+/-, SCAD+/-) and wild-type.
      We found that approximately 33% of mice with any of the combined mutant genotypes
      tested became hypothermic during a cold challenge. All wild-type and single
      heterozygous mice maintained normal body temperature throughout a cold challenge.
      Despite development of hypothermia in some double heterozygous mice, blood
      glucose concentrations remained normal. Biochemical screening by acylcarnitine
      and fatty acid analyses demonstrated results that varied by genotype. Thus,
      physiologic reduction of the beta-oxidation pathway, characterized as cold
      intolerance, occurred in mice with double or triple heterozygosity; however, the
      derangement was milder than in mice homozygous for any of these mutations. These
      results substantiate the concept of synergistic heterozygosity and illustrate the
      potential complexity involved in diagnosis and characterization of inborn errors
      of fatty acid metabolism in humans.

PMID- 15862273
TI  - Gallstones in chronic liver disease.
AB  - Gallstones occur more commonly in patients with cirrhosis. The incidence
      increases with severity of liver disease, and the majority remain asymptomatic.
      When symptoms do occur, morbidity and mortality are much higher than in
      noncirrhotic patients. Asymptomatic gallstones in cirrhotic patients are best
      managed conservatively with close follow-up and surgery if symptoms occur. The
      management of asymptomatic gallstones found incidentally at abdominal surgery for
      another indication is controversial. Laparoscopic cholecystectomy is the
      treatment of choice for symptomatic cholelithiasis in patients with well
      compensated liver disease, whereas patients with choledocholithiasis are best
      managed endoscopically. Symptomatic cholelithiasis in the decompensated patient
      remains a challenge, and these patients are best managed in specialized
      hepatobiliary centers. This review examines the evidence currently available on
      gallstones in chronic liver disease and the factors that influence its
      management.

PMID- 15862276
TI  - The pathogenesis of molybdenum cofactor deficiency, its delay by maternal
      clearance, and its expression pattern in microarray analysis.
AB  - Molybdenum cofactor (Moco)-deficiency is a lethal autosomal recessive disease,
      for which until now no effective therapy is available. The biochemical hallmark
      of this disorder is the inactivity of the Moco-dependent sulfite oxidase, which
      results in elevated sulfite and diminished sulfate levels throughout the
      organism. In humans, Moco-deficiency results in neurological damage, which is
      apparent in untreatable seizures and various brain dysmorphisms. We have recently
      described a murine model for Moco-deficiency, which reflects all enzyme and
      metabolite changes observed in the patients, and an efficient therapy using a
      biosynthetic precursor of Moco has been established in this animal model. We now
      analyzed these mice in detail and excluded morphological brain damage, while
      expression analysis with microarrays indicates a massive cell death program. This
      neuronal damage appears to be triggered by elevated sulfite levels and is
      ameliorated in affected embryos by maternal clearance.

PMID- 15862277
TI  - UDP-galactose pyrophosphorylase in mice with galactose-1-phosphate
      uridyltransferase deficiency.
AB  - UDP-glucose pyrophosphorylase (E.C. 2.7.7.9), encoded by ugp, provides UDP
      glucose which is critical to the synthesis of glycogen, and also catalyzes the
      reaction between UTP and galactose-1-phosphate, yielding UDP-galactose. This
      activity of UDP-gal pyrophosphorylase (UDP-galPP) suggests a role in an alternate
      pathway for galactose metabolism in patients with deficiency of galactose-1
      phosphate uridyltransferase (GALT). We examined the effects of GALT deficiency
      and dietary galactose on UDP-glucose pyrophosphorylase (UDP-gluPP) and UDP
      galactose pyrophosphorylase activity and ugp expression in liver of mice with
      homozygous deletion of the critical regions of galt. Activity with glucose-1
      phosphate as substrate was significantly higher than that with galactose-1
      phosphate. In liver from mice with GALT deficiency (G/G), UDP-galPP activity
      appeared to be lower than that measured in liver from control (N/N) animals. This
      difference disappeared when the N/N tissue homogenate was dialyzed to remove
      residual UDP-glucose, confirming that careful elimination of residual GALT
      activity is necessary, since GALT has 1000-fold greater activity toward galactose
      1-phosphate than that of UDP-galPP in liver homogenates. Prior exposure to
      conventional mouse chow, high galactose chow, and high glucose chow did not alter
      UDP-glu PP or UDP-galPP activity. Steady state UGP mRNA levels were determined in
      tissues from normal and G/G animals. UGP expression was highest in liver, and did
      not differ by genotype or exposure to high galactose chow. UDP-galPP activity may
      account for unexplained ability to oxidize galactose in animals with no GALT
      activity, but is insufficient to alter accumulation of galactose metabolites.

PMID- 15862278
TI  - A homology model for human alpha-l-iduronidase: insights into human disease.
AB  - Genotype-phenotype correlations in genetic diseases for which missense mutations
      lead to disease remain a challenge. This is particularly true for diseases caused
      by alterations of proteins for which no three-dimensional structure is available.
      One such disease is Mucopolysaccharidosis type I, a disorder arising from a lack
      of activity of the lysosomal enzyme alpha-l-iduronidase (IDUA, EC 3.2.1.76). This
      deficiency compromises the degradation pathway of glycosaminoglycans such as
      heparan sulfate and dermatan sulfate, leading to substrate accumulation, which
      ultimately results in a multisystem disorder. Patients with IDUA deficiency have
      a wide spectrum of disease ranging from an early onset, rapidly progressive form
      leading to death in the first decade of life, to an attenuated disease which
      manifests in adolescence and leads to progressive joint and cardiac disease but
      is associated with a normal life span. Many patients fit into a disease phenotype
      intermediate to these extremes. While a number of point mutations have been
      described as leading to varying degrees of disease severity, a structural basis
      for these genotype-phenotype correlations has not been available owing to the
      lack of a three-dimensional structure for IDUA. A homology model for the IDUA
      enzyme was constructed based on the recently solved crystal structure of the beta
      xylosidase from Thermoanaerobacterium saccharolyticum (XyTS, EC 3.2.1.37), both
      of which belong to the same sequence-related family (CAZY family 39). This model
      provides insights into why certain point mutations produce severely misfolded
      proteins and thus lead to severe disease, and why other mutations produce
      proteins with only minor structural perturbations and therefore the attenuated
      form of the disease.

PMID- 15862280
TI  - Essential role of citrate export from mitochondria at early differentiation stage
      of 3T3-L1 cells for their effective differentiation into fat cells, as revealed
      by studies using specific inhibitors of mitochondrial di- and tricarboxylate
      carriers.
AB  - 1,2,3-Benzenetricarboxylate (BTA) and n-butylmalonate (BM), specific inhibitors
      of the mitochondrial tricarboxylate and dicarboxylate carrier, respectively, have
      been used to study the contribution of citrate export from mitochondria to the
      accumulation of fat in 3T3-L1 cells. Continuous treatment of the cells with BTA
      or BM for 5 days after the induction of differentiation caused a significant
      reduction in fat accumulation in the cells in an inhibitor concentration
      dependent manner. These inhibitory effects of BTA and BM were not due to their
      side effects on DNA replication, since similar inhibition of fat accumulation was
      not observed with ordinary inhibitors of DNA replication. A similar reduction in
      fat accumulation was also observed when the cells were treated with BTA or BM for
      only 2 days just after induction of differentiation. However, interestingly,
      treatment of the cells with an inhibitor starting 2 days after the induction did
      not result in reduced fat accumulation. Furthermore, Northern analysis clearly
      indicated that transcript levels of peroxisome proliferator-activated receptor
      gamma (PPARgamma) and adipose-type fatty acid binding protein (A-FABP) were well
      correlated with the levels of fat accumulation. These results clearly indicate
      the essential role of citrate export from the mitochondrial matrix to the cytosol
      at the early differentiation stage of 3T3-L1 cells for their effective
      differentiation into fat cells.

PMID- 15862279
TI  - Increased susceptibility of spinal muscular atrophy fibroblasts to camptothecin
      induced cell death.
AB  - Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions or
      mutations in the telomeric copy of the survival motor neuron (SMN1) gene.
      Although the SMN protein has been implicated in the biogenesis of
      ribonucleoprotein complexes and RNA processing, it is not clear how these
      functions contribute to the pathogenesis of SMA. To gain a further understanding
      of SMN function, we have investigated its role in cell survival in skin
      fibroblasts derived from SMA patients and age-matched controls. SMA fibroblasts
      exposed to camptothecin, a specific inhibitor of DNA topoisomerase I,
      consistently showed cell death at a lower concentration than normal controls.
      Treatment with other cell death-inducing agents did not cause differences in
      survival of SMA fibroblasts as compared with control fibroblasts. Camptothecin
      treatment resulted in activation of caspase-3 with generation of the caspase-3
      cleavage product, poly ADP-ribose polymerase (PARP). Depletion of SMN protein by
      RNA interference in control fibroblasts increased caspase-3 activity, whereas
      transfection of SMA fibroblasts with wild-type SMN decreased caspase-3 activity.
      Our data demonstrate that SMA fibroblasts are more prone to some, but not all,
      death-stimuli. Vulnerability to death-stimuli is associated with decreased levels
      of SMN protein and is mediated by activation of caspase-3.

PMID- 15862281
TI  - Calpain inhibition and insulin action in cultured human muscle cells.
AB  - Variation in the calpain 10 gene has been reported to increase susceptibility to
      type 2 diabetes. Part of this susceptibility appears to be mediated by a decrease
      in whole body insulin sensitivity. As skeletal muscle is the primary tissue site
      of the peripheral insulin resistance in type 2 diabetes, the aim of this study
      was to use a human skeletal muscle cell culture system to explore the effects of
      calpain inhibition on insulin action. Calpain 10 mRNA and protein expression was
      examined in cultured myoblasts, myotubes, and whole skeletal muscle from non
      diabetic subjects using RT-PCR and Western blotting. Changes in insulin
      stimulated glucose uptake and glycogen synthesis in response to the calpain
      inhibitors ALLN and ALLM were measured. Calpain 10 expression was confirmed in
      cultured human myoblasts, myotubes, and native skeletal muscle. Insulin
      stimulated glucose uptake was significantly decreased following preincubation
      with ALLN [404+/-40 vs 505+/-55 (mean+/-SEM)pmol/mg/min; with vs without ALLN: p
      = 0.04] and ALLM [455+/-38 vs 550+/-50 pmol/mg/min; with vs without ALLM: p =
      0.025] in day 7 fused myotubes, but not in myoblasts. Neither ALLN nor ALLM
      affected insulin-stimulated glycogen synthesis in myoblasts or myotubes. These
      studies confirm calpain 10 expression in cultured human muscle cells and support
      a role for calpains in insulin-stimulated glucose uptake in human skeletal muscle
      cells that may be relevant to the pathogenesis of the peripheral insulin
      resistance in type 2 diabetes.

PMID- 15862282
TI  - Adiponectin and resistin serum levels in women with polycystic ovary syndrome
      during oral glucose tolerance test: a significant reciprocal correlation between
      adiponectin and resistin independent of insulin resistance indices.
AB  - Polycystic ovary syndrome (PCOS) is associated with an increased incidence of
      insulin resistance (IR), obesity, and type 2 diabetes. Resistin, an
      adipocytokine, may represent a link between obesity, and these metabolic
      disorders. There is also evidence that inflammation is a hyperresistinemic state
      in humans, and cytokine induction of resistin may contribute to insulin
      resistance in endotoxemia, obesity, and other inflammatory states. In contrast,
      adiponectin, increases insulin sensitivity, improves glucose tolerance, inhibits
      inflammatory pathways, while adenovirus-expressed adiponectin reduces
      atherosclerotic lesions in a mouse model of atherosclerosis. We aimed to assess,
      in women with PCOS, whether there is a relationship between adiponectin and
      resistin and the indices of IR, and whether serum levels of these adipocytokines
      are altered by glucose-induced hyperinsulinaemia. Serum levels of resistin and
      adiponectin were measured at 0, 60, and 120 min during 75 g oral glucose
      tolerance test (OGTT), in 19 women with PCOS, age 36.3+/-11.4 years (mean+/-SD),
      body mass index (BMI) 29.3+/-7.7 kg/m2, and correlated with the indices of IR,
      such as HOMA-IR, QUICKI, and the insulin resistance index calculated from glucose
      and insulin levels obtained during OGTT. There was no change in resistin
      concentrations (7.31+/-4.58, 7.47+/-5.40, 7.22+/-5.12 pg/ml, at 0, 60, and 120
      min of OGTT, respectively, P = 0.77), but there was an increase in adiponectin
      from 11.32+/-4.64 microg/ml at baseline to 14.78+/-7.41 microg/ml, at 120 min of
      OGTT (P < 0.01). The magnitude of the overall rise in adiponectin was greater
      from 60 to 120 min (from 12.31+/-5.72 to 14.78+/-7.41 microg/ml, P < 0.006).
      Neither resistin, nor adiponectin correlated with the indices of IR, lipids, or
      other hormonal parameters of the PCOS. There was, however, a significant negative
      correlation between serum resistin and adiponectin (P = 0.001). In conclusion, we
      observed a strong negative correlation between serum adiponectin and resistin,
      despite the lack of direct correlation with the indices of IR. Given the opposite
      effects of resistin and adiponectin on the inflammatory process, we speculate
      that relative proportion of adiponectin-to-resistin might potentially influence
      cardiometabolic risk in women with the PCOS independently of IR parameters. The
      observed increase in adiponectin during OGTT requires further study.

PMID- 15862283
TI  - Lesch-Nyhan disease in a female with a clinically normal monozygotic twin.
AB  - Lesch-Nyhan disease (LND) is an inborn error of purine metabolism caused by
      defective activity of the enzyme hypoxanthine guanine phosphoribosyl transferase
      (HPRT, EC 2.4.2.8), resulting from mutation in the corresponding gene on the long
      arm of the X chromosome (Xq26). The classic phenotype occurs almost exclusively
      in males and is characterized by hyperuricemia, mental retardation, severe
      dystonia, and self-injurious behavior. Heterozygous carrier females are usually
      clinically normal. However, a small number of clinically affected females have
      been described. In all previous cases there was a mutation in one HPRT allele and
      non-random inactivation of the X chromosome carrying the normal HPRT gene. We
      have analyzed a female MZ twin pair discordant for Lesch-Nyhan disease. The
      mother and both twins are heterozygous carriers of a HPRT splicing mutation (IVS8
      + 4A > G; c.609 + 4A > G) and all three express the mutant allele at similar
      frequencies in peripheral blood T cells. The mother and one sister are clinically
      normal. In the affected twin, the clinical phenotype is classical for Lesch-Nyhan
      disease, despite the fact that HPRT activity in the blood was also normal. X
      inactivation analysis showed a skewed pattern in the fibroblasts of the affected
      twin sister, with the X chromosome carrying the normal HPRT allele preferentially
      inactivated. As in many other reported cases of X-linked diseases, the discordant
      phenotype of the two monozygous twin sisters suggests that the process
      responsible for monozygotic twinning can trigger skewed X inactivation.

PMID- 15862284
TI  - Normal HPRT coding region in a male with gout due to HPRT deficiency.
AB  - A deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT;
      EC 2.4.2.8) is associated with a spectrum of disease that ranges from gouty
      arthritis (OMIM 300323) to the more severe Lesch-Nyhan syndrome (OMIM 300322). To
      date, all cases of HPRT deficiency have shown a mutation within the HPRT cDNA. In
      the present study of an individual with gout due to HPRT deficiency, we found a
      normal HPRT cDNA sequence. This is the first study to provide an example of HPRT
      deficiency which appears to be due to a defect in the regulation of the gene.

PMID- 15862285
TI  - Drug resistance in malaria: its population biology and implications for control.

PMID- 15862286
TI  - Adaptive evolution of MRGX2, a human sensory neuron specific gene involved in
      nociception.
AB  - MRGX2, a G-protein-coupled receptor, is specifically expressed in the sensory
      neurons of the human peripheral nervous system and involved in nociception. Here,
      we studied DNA polymorphism patterns and evolution of the MRGX2 gene in world
      wide human populations and the representative nonhuman primate species. Our
      results demonstrated that MRGX2 had undergone adaptive changes in the path of
      human evolution, which were likely caused by Darwinian positive selection. The
      patterns of DNA sequence polymorphisms in human populations showed an excess of
      derived substitutions, which against the expectation of neutral evolution,
      implying that the adaptive evolution of MRGX2 in humans was a relatively recent
      event. The reconstructed secondary structure of the human MRGX2 revealed that
      three of the four human-specific amino acid substitutions were located in the
      extra-cellular domains. Such critical substitutions may alter the interactions
      between MRGX2 protein and its ligand, thus, potentially led to adaptive changes
      of the pain-perception-related nervous system during human evolution.

PMID- 15862287
TI  - Why females live longer than males? Importance of the upregulation of longevity
      associated genes by oestrogenic compounds.
AB  - Females live longer than males in many mammalian species, including humans.
      Mitochondria from females produce approximately half the amount of H(2)O(2) than
      males. We have found that females behave as double transgenics overexpressing
      both superoxide dismutase and glutathione peroxidase. This is due to oestrogens
      that act by binding to the estrogen receptors and subsequently activating the
      mitogen activated protein (MAP) kinase and nuclear factor kappa B (NF-kappaB)
      signalling pathways. Phytoestrogens mimic the protective effect of oestradiol
      using the same signalling pathway. The critical importance of upregulating
      antioxidant genes, by hormonal and dietary manipulations, in order to increase
      longevity is discussed.

PMID- 15862288
TI  - Thermal stability of outer membrane protein porin from Paracoccus denitrificans:
      FT-IR as a spectroscopic tool to study lipid-protein interaction.
AB  - Lipid protein interactions play a key role in the stability and function of
      various membrane proteins. Earlier we have reported the extreme thermal stability
      of porin from Paracoccus denitrificans reconstituted into liposomes. Here, we
      used Fourier transform infrared spectroscopy for a label free analysis of the
      global secondary structural changes and local changes in the tyrosine
      microenvironment. Our results show that a mixed lipid system (non-uniform
      bilayer) optimizes the thermal stability of porin as compared to the porin in
      pure lipids (uniform bilayer) or detergent micelles. This is in line with the
      fact that the bacterial outer membrane is a dynamic system made up of lipids of
      varying chain lengths, head groups and the barrel wall height contacting the
      membrane is uneven.

PMID- 15862289
TI  - Cytokines upregulate vascular endothelial growth factor secretion by human airway
      smooth muscle cells: Role of endogenous prostanoids.
AB  - Here, we report that vascular endothelial growth factor (VEGF)-A secretion by
      human airway smooth muscle cells was increased by interleukin 1 beta (IL-1beta)
      and transforming growth factor beta (TGFbeta). IL-1beta and TGFbeta induced cyclo
      oxygenase (COX)-2 protein and increased prostaglandin E(2) (PGE(2)). Both IL
      1beta and TGFbeta increased VEGF-A(165) mRNA and VEGF promoter luciferase
      construct activity, in addition VEGF-A protein was inhibited by actinomycin D
      suggesting transcriptional regulation. The COX inhibitors indomethacin and NS398
      inhibited IL-1beta but not TGFbeta mediated VEGF-A production. Furthermore, the
      effect of the COX inhibitors was overcome by adding exogenous PGE(2). In
      conclusion, IL-1beta increases VEGF-A secretion by COX-2 derived PGE(2)
      production whereas TGFbeta uses COX-independent pathways.

PMID- 15862290
TI  - Transcriptional induction of Smurf2 ubiquitin ligase by TGF-beta.
AB  - Smad ubiquitination regulatory factor 2 (Smurf2), a ubiquitin ligase for Smads,
      plays critical roles in the regulation of transforming growth factor-beta (TGF
      beta)-Smad signaling via ubiquitin-dependent degradation of Smad2 and Smad7. We
      found that TGF-beta stimulates Smurf2 expression. TGF-beta activated the Smurf2
      promoter in a TGF-beta responsive cell lines, whereas IL-1alpha, PDGF and
      epidermal growth factor did not. TGF-beta-mediated Smurf2 promoter activation was
      inhibited by Smad7 or an activin receptor-like kinase 5 inhibitor but not by
      dominant negative Smad or disruption of Smad-binding elements in the promoter.
      Moreover, inhibition of the phosphatidil inositol 3 kinase (PI3K)/Akt pathway
      suppressed TGF-beta-mediated Smurf2 induction. These results suggest that TGF
      beta stimulates Smurf2 expression by Smad-independent pathway such as PI3K/Akt
      pathway via TGF-beta receptor.

PMID- 15862291
TI  - Meningoencephalitis associated with passive immunization of a transgenic murine
      model of Alzheimer's amyloidosis.
AB  - Immunization against the Abeta peptide reverses the pathologic and behavioral
      manifestations of Alzheimer's disease in murine models. Since active immunization
      is associated with an autoimmune meningoencephalitis in a subset of humans,
      passive transfer of anti-Abeta immunoglobulin is being pursued as a potentially
      safer alternative. We have identified cases of meningoencephalitis subsequent to
      peripheral and intracerebral passive immunization of Tg2576 mice. The vasocentric
      mononuclear infiltrate localized only to brain regions affected by Abeta amyloid
      deposits suggesting that the inflammatory reaction was Abeta specific. This
      report indicates that current passive immunization in humans should proceed with
      careful regard for autoimmune complications.

PMID- 15862292
TI  - Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not
      selectively expressed on tumour endothelium.
AB  - Fibroblasts are a diverse cell type and display clear topographic differentiation
      and positional memory. In a screen for fibroblast specific markers we have
      characterized four monoclonal antibodies to endosialin (TEM1/CD248). Previous
      studies have reported that endosialin is a tumour endothelium marker and is
      localized intracellularly. We demonstrate conclusively that endosialin is a cell
      surface glycoprotein and is predominantly expressed by fibroblasts and a subset
      of pericytes associated with tumour vessels but not by tumour endothelium. These
      novel antibodies will facilitate the isolation and classification of fibroblast
      and pericyte lineages as well as the further functional analysis of endosialin.

PMID- 15862293
TI  - Transcriptional regulation of connective tissue growth factor by sphingosine 1
      phosphate in rat cultured mesangial cells.
AB  - Connective tissue growth factor (CTGF) is induced by transforming growth factor
      beta (TGF-beta) via Smad activation in mesangial cells. We recently reported that
      sphingosine 1-phosphate (S1P) induces CTGF expression in rat cultured mesangial
      cells. However, the mechanism by which S1P induces CTGF expression is unknown.
      The present study revealed that S1P-induced CTGF expression is mediated via
      pertussis toxin-insensitive pathways, which are involved in the activation of
      small GTPases of the Rho family and protein kinase C. We also showed by
      luciferase reporter assays and chromatin immunoprecipitation that S1P induces
      CTGF expression via Smad activation as TGF-beta does.

PMID- 15862294
TI  - Roles of Mg2+ in TPP-dependent riboswitch.
AB  - We quantified the effect of Mg(2+) on thiamine pyrophosphate (TPP) binding to TPP
      dependent thiA riboswitch RNA. The association constant of TPP binding to the
      riboswitch at 20 degrees C increased from 1.2 x 10(6) to 50 x 10(6) M(-1) as the
      Mg(2+) concentration increased from 0 to 1 mM. Furthermore, circular dichroic
      spectra under various conditions showed that 1 mM Mg(2+) induced a local
      structural change of the riboswitch, which might be pivotal for TPP binding.
      These results indicate that a physiological concentration of Mg(2+) can regulate
      TPP binding to the thiA riboswitch.

PMID- 15862295
TI  - The presence of valine at residue 129 in human prion protein accelerates amyloid
      formation.
AB  - The polymorphism at residue 129 of the human PRNP gene modulates disease
      susceptibility and the clinico-pathological phenotypes in human transmissible
      spongiform encephalopathies. The molecular mechanisms by which the effect of this
      polymorphism are mediated remain unclear. It has been shown that the folding,
      dynamics and stability of the physiological, alpha-helix-rich form of recombinant
      PrP are not affected by codon 129 polymorphism. Consistent with this, we have
      recently shown that the kinetics of amyloid formation do not differ between
      protein containing methionine at codon 129 and valine at codon 129 when the
      reaction is initiated from the alpha-monomeric PrP(C)-like state. In contrast, we
      have shown that the misfolding pathway leading to the formation of beta-sheet
      rich, soluble oligomer was favoured by the presence of methionine, compared with
      valine, at position 129. In the present work, we examine the effect of this
      polymorphism on the kinetics of an alternative misfolding pathway, that of
      amyloid formation using partially folded PrP allelomorphs. We show that the
      valine 129 allelomorph forms amyloids with a considerably shorter lag phase than
      the methionine 129 allelomorph both under spontaneous conditions and when seeded
      with pre-formed amyloid fibres. Taken together, our studies demonstrate that the
      effect of the codon 129 polymorphism depends on the specific misfolding pathway
      and on the initial conformation of the protein. The inverse propensities of the
      two allelomorphs to misfold in vitro through the alternative oligomeric and
      amyloidogenic pathways could explain some aspects of prion diseases linked to
      this polymorphism such as age at onset and disease incubation time.

PMID- 15862296
TI  - Distribution profile of inositol 1,4,5-trisphosphate receptor isoforms in adrenal
      chromaffin cells.
AB  - Given the importance of inositol 1,4,5-trisphosphate receptor (IP(3)R)/Ca(2+)
      channels in the control of intracellular Ca(2+) concentrations, we determined the
      relative concentrations of the IP(3)R isoforms in subcellular organelles, based
      on serially sectioned electron micrographs. The endoplasmic reticulum (ER) was
      estimated to contain 15-20% of each of the three IP(3)R isoforms while secretory
      granules contained 58-69%. The nucleus contained approximately 15% each of IP(3)R
      1 and -2, but 25% of IP(3)R-3, whereas the plasma membrane contained
      approximately 1% or less of each. These suggested that secretory granules, the
      nucleus and ER are at the center of IP(3)-dependent intracellular Ca(2+) control
      mechanisms in chromaffin cells.

PMID- 15862297
TI  - HDM2 negatively affects the Chk2-mediated phosphorylation of p53.
AB  - By GST pull downs and co-immunoprecipitation analyses we found that recombinant
      Chk2 and HDM2 can form stable complexes in vitro. Chk2/HDM2 complexes were also
      detected in transfected Cos-1 cells over-expressing both proteins. Furthermore,
      we show that HDM2, as would be expected, severely affects the Chk2-catalyzed
      phosphorylation of p53. HDM2 itself is only slightly phosphorylated by Chk2.
      However, whereas HDM2 inhibits the Chk2-catalyzed p53 phosphorylation, HDM2
      phosphorylation by Chk2 doubles in the presence of p53. The significance of the
      HDM2 phosphorylation is unknown, but it is possible that it might influence the
      stability of the HDM2/p53 complex.

PMID- 15862298
TI  - Induction of IGFBP-1 expression by amino acid deprivation of HepG2 human hepatoma
      cells involves both a transcriptional activation and an mRNA stabilization due to
      its 3'UTR.
AB  - A dramatic overexpression of IGFBP-1 is responsible for growth inhibition, in
      response to a low-protein diet feeding. It has been demonstrated that a fall in
      the amino acid concentration was directly responsible for IGFBP-1 induction. In
      this report, we sought to determine the mechanism by which amino acid limitation
      upregulates IGFBP-1 expression. Our results show that both transcriptional
      activation and mRNA stabilization are involved. We also demonstrate that (i) the
      mGCN2/ATF4 pathway is not involved in this regulation and (ii) the 3'UTR of IGFBP
      1 mRNA is responsible for its destabilization and regulates its stability in
      response to amino acid starvation.

PMID- 15862299
TI  - MEF2C DNA-binding activity is inhibited through its interaction with the
      regulatory protein Ki-1/57.
AB  - Myocyte enhancer factor (MEF2) are MADS box transcription factors that play
      important roles in the regulation of myogenesis and morphogenesis of muscle
      cells. MEF2 proteins are activated by mechanical overload in the heart. In this
      study, we found the interaction of MEF2C with the regulatory protein Ki-1/57
      using yeast two-hybrid system. This interaction was confirmed by GST-pull down
      assay in vitro and by co-immunoprecipitation in vivo. This interaction is also
      dependent on pressure overload in the heart. Co-imunoprecipitation assay with
      anti-MEF2 and anti-Ki-1/57 antibodies demonstrated a basal association between
      these proteins in the left ventricles of control rats. Pressure overload caused a
      reduction in this association. Ki-1/57 co-localizes with MEF2 in the nucleus of
      myocytes of control rats. However, after submitting the animals to pressure
      overload Ki-1/57 leaves the nucleus thereby decreasing this co-localization. Ki
      1/57 also exerts an inhibitory effect upon MEF2C DNA binding activity. These
      results suggest that Ki-1/57 is a new interacting partner of MEF2 protein and may
      be involved in the regulation of MEF2 at the onset of hypertrophy.

PMID- 15862300
TI  - The nucleocapsid protein of SARS coronavirus has a high binding affinity to the
      human cellular heterogeneous nuclear ribonucleoprotein A1.
AB  - The nucleocapsid (N) protein of SARS coronavirus (SARS_CoV) is a major structural
      component of virions, which appears to be a multifunctional protein involved in
      viral RNA replication and translation. Heterogeneous nuclear ribonucleoprotein A1
      (hnRNP A1) is related to the pre-mRNA splicing in the nucleus and translation
      regulation in the cytoplasm. In this report, based on the relevant biophysical
      and biochemical assays, the nucleocapsid protein of SARS_CoV (SARS_N) was
      discovered to exhibit high binding affinity to human hnRNP A1. GST pull-down
      results clearly demonstrated that SARS_N protein could directly and specifically
      bind to human hnRNP A1 in vitro. Yeast two-hybrid assays further indicated in
      vivo that such binding relates to the fragment (aa 161-210) of SARS_N and the Gly
      rich domain (aa 203-320) of hnRNP A1. Moreover, kinetic analyses by surface
      plasmon resonance (SPR) technology revealed that SARS_N protein has a specific
      binding affinity against human hnRNP A1 with K(D) at 0.35 +/- 0.02 microM (k(on)
      = 5.83 +/- 0.42 x 10(3) M(-1)s(-1) and k(off) = 2.06 +/- 0.12 x 10(-3)s(-1)). It
      is suggested that both SARS_N and hnRNP A1 proteins are possibly within the
      SARS_CoV replication/transcription complex and SARS_N/human hnRNP A1 interaction
      might function in the regulation of SARS_CoV RNA synthesis. In addition, the
      determined results showed that SARS_N protein has only one binding domain for
      interacting with human hnRNP A1, which is different from the mouse hepatitis
      virus (MHV) binding case where the nucleocapsid protein of MHV (MHV_N) was found
      to have two binding domains involved in the MHV_N/hnRNP A1 interaction, thereby
      suggesting that SARS_N protein might carry out a different binding mode to bind
      to human hnRNP A1 for its further function performance in comparison with MHV_N.

PMID- 15862301
TI  - Transfer RNA recognition by class I lysyl-tRNA synthetase from the Lyme disease
      pathogen Borrelia burgdorferi.
AB  - Borrelia burgdorferi and other spirochetes contain a class I lysyl-tRNA
      synthetase (LysRS), in contrast to most eubacteria that have a canonical class II
      LysRS. We analyzed tRNA(Lys) recognition by B. burgdorferi LysRS, using two
      complementary approaches. First, the nucleotides of B. burgdorferi tRNA(Lys) in
      contact with B. burgdorferi LysRS were determined by enzymatic footprinting
      experiments. Second, the kinetic parameters for a series of variants of the B.
      burgdorferi tRNA(Lys) were then determined during aminoacylation by B.
      burgdorferi LysRS. The identity elements were found to be mostly located in the
      anticodon and in the acceptor stem. Transplantation of the identified identity
      elements into the Escherichia coli tRNA(Asp) scaffold endowed lysylation activity
      on the resulting chimera, indicating that a functional B. burgdorferi lysine tRNA
      identity set had been determined.

PMID- 15862302
TI  - Quantitative aspects of endocytic activity in lipid-mediated transfections.
AB  - Variation in transfection efficiency observed in different cell-types is poorly
      understood. To investigate the influence of endocytic activity on lipid-mediated
      transfections, we have monitored both the processes in 12 different cell-types.
      The endocytic activity shows a strong positive correlation (P < 0.01), with
      transfection efficiency. Treatment with wortmannin resulted in cell-type
      dependent inhibition of transfection. Studies on M-phase cells by confocal
      microscopy show that compared to interphase cells, uptake of cationic liposomes
      was substantially reduced. In addition, transfection efficiency of cells in
      mitotic phase was inhibited by >70% compared to controls. Our study based on
      several cell-types demonstrates for the first time that quantitative aspects of
      endocytosis have decisive influence on the overall process of lipid-mediated
      transgene expression.

PMID- 15862303
TI  - Functionality of nitrated acetylcholine receptor: the two-step formation of
      nitrotyrosines reveals their differential role in effectors binding.
AB  - The presence of nitrotyrosines is associated with several neurodegenerative
      pathologies. We evaluated the functionality of the nicotinic acetylcholine
      receptor possessing nitrotyrosines. The spectrum of the nitrated receptor
      displays an absorption band characteristic of ortho-nitrophenol. The presence of
      carbamylcholine in the agonist site prevented the effect of nitration by
      tetranitromethane in some conditions. The nitration occurred with two discrete
      steps and pointed out the differential involvement of tyrosines in the binding of
      acetylcholine and neurotoxin. We concluded that at least two residues involved in
      agonist binding can be nitrated, which bring similar contributions to the binding
      energy of the neurotransmitter.

PMID- 15862304
TI  - Evidence of differential pH regulation of the Arabidopsis vacuolar Ca2+/H+
      antiporters CAX1 and CAX2.
AB  - The Arabidopsis Ca(2+)/H(+) antiporters cation exchanger (CAX) 1 and 2 utilise an
      electrochemical gradient to transport Ca(2+) into the vacuole to help mediate
      Ca(2+) homeostasis. Previous whole plant studies indicate that activity of
      Ca(2+)/H(+) antiporters is regulated by pH. However, the pH regulation of
      individual Ca(2+)/H(+) antiporters has not been examined. To determine whether
      CAX1 and CAX2 activity is affected by pH, Ca(2+)/H(+) antiport activity was
      measured in vacuolar membrane vesicles isolated from yeast heterologously
      expressing either transporter. Ca(2+) transport by CAX1 and CAX2 was regulated by
      cytosolic pH and each transporter had a distinct cytosolic pH profile. Screening
      of CAX1/CAX2 chimeras identified an amino acid domain within CAX2 that altered
      the pH-dependent Ca(2+) transport profile so that it was almost identical to the
      pH profile of CAX1. Results from mutagenesis of a specific His residue within
      this domain suggests a role for this residue in pH regulation.

PMID- 15862305
TI  - Catalytic properties of glutathione-binding residues in a tau class glutathione
      transferase (PtGSTU1) from Pinus tabulaeformis.
AB  - Glutathione transferases (GSTs) play important roles in stress tolerance and
      detoxification in plants. However, there is extremely little information on the
      molecular characteristics of GSTs in gymnosperms. In a previous study, we cloned
      a tau class GST (PtGSTU1) from a gymnosperm (Pinus tabulaeformis) for the first
      time. Based on the N-terminal amino acid sequence identity to the available
      crystal structures of plant tau GSTs, Ser13, Lys40, Ile54, Glu66 and Ser67 of
      PtGSTU1 were proposed as glutathione-binding (G-site) residues. The importance of
      Ser13 as a G-site residue was investigated previously. The functions of Lys40,
      Ile54, Glu66 and Ser67 of PtGSTU1 are examined in this study through site
      directed mutagenesis. Enzyme assays and thermal stability measurements on the
      purified recombinant PtGSTU1 showed that substitution at each of these sites
      significantly affects the enzyme's substrate specificity and affinity for GSH,
      and these residues are essential for maintaining the stability of PtGSTU1. The
      results of protein expression and refolding analyses suggest that Ile54 is
      involved in the protein folding process. The findings demonstrate that the
      aforementioned residues are critical components of active sites that contribute
      to the enzyme's catalytic activity and structural stability.

PMID- 15862306
TI  - Interactions of the cytotoxic RNase A dimers with the cytosolic ribonuclease
      inhibitor.
AB  - Ribonuclease A (RNase A) dimers have been recently found to be endowed with some
      of the special, i.e., non-catalytic biological activities of RNases, such as
      antitumor and aspermatogenic activities. These activities have been so far
      attributed to RNases which can escape the neutralizing action of the cytosolic
      RNase inhibitor (cRI). However, when the interactions of the two cytotoxic RNase
      A dimers with cRI were investigated in a quantitative fashion and at the
      molecular level, the dimers were found to bind cRI with high affinity and to form
      tight complexes.

PMID- 15862307
TI  - A targeted antioxidant reveals the importance of mitochondrial reactive oxygen
      species in the hypoxic signaling of HIF-1alpha.
AB  - Exposure to limiting oxygen in cells and tissues induce the stabilization and
      transcriptional activation of the hypoxia-inducible factor 1 alpha (HIF-1alpha)
      protein, a key regulator of the hypoxic response. Reactive oxygen species (ROS)
      generation has been implicated in the stabilization of HIF-1alpha during this
      response, but this is still a matter of some debate. In this study we utilize a
      mitochondria-targeted antioxidant, mitoubiquinone (MitoQ), and examine its
      effects on the hypoxic stabilization of HIF-1alpha. Our results show that under
      conditions of reduced oxygen (3% O(2)), MitoQ ablated the hypoxic induction of
      ROS generation and destabilized HIF-1alpha protein. This in turn led to an
      abrogation of HIF-1 transcriptional activity. Normoxic stabilization of HIF
      1alpha, on the other hand, was unchanged in the presence of MitoQ suggesting that
      ROS were not involved. This study strongly suggests that mitochondrial ROS
      contribute to the hypoxic stabilization of HIF-1alpha.

PMID- 15862308
TI  - A 5' intronic splice site polymorphism leads to a null allele of the P2X7 gene in
      1-2% of the Caucasian population.
AB  - The P2X(7) gene is important for the innate immune response but known
      polymorphisms do not explain all subjects with loss of P2X(7) function. A splice
      site mutation (g-->t) was found at position +1 of the first intron of the P2X(7)
      gene in 7 of 336 Caucasians and 1 of 39 subjects of Indian ethnicity. All eight
      subjects were heterozygous for the uncommon 1513A-->C polymorphism of the P2X(7)
      gene. RT-PCR and sequencing showed the splice site mutation was on the 1513C
      allele in the Caucasians and on the 1513A allele in the Indian subject. The
      splice site mutation is an inherited polymorphism and gives rise to a P2X(7) null
      allele in 1-2% of the Caucasian population.

PMID- 15862309
TI  - Molecular basis of the allosteric mechanism of cAMP in the regulatory PKA
      subunit.
AB  - The second messenger cyclic Adenosine MonoPosphate (cAMP) mediates many
      biological process by interacting with structurally conserved nucleotide binding
      domains (cNBD's). Here, we use molecular dynamics simulations on RIIbeta-PKA, one
      of the best characterized members of the cNBD family, in presence and absence of
      cAMP. The results of our calculations are fully consistent with the available
      experimental data and suggest that the key factor of the cAMP allosteric
      mechanism in cNBDS's is the increased flexibility of the protein upon ligand
      release along with a mechanical coupling between helical segments. In addition,
      our calculations provide a rationale for the experimentally observed cAMP
      selective binding to PKA.

PMID- 15862310
TI  - Oligomerization and assembly of the matrix protein of Borna disease virus.
AB  - The matrix protein M of Borna disease virus (BDV) is a constituent of the viral
      envelope covering the inner leaflet of the lipid bilayer. BDV-M was expressed as
      recombinant protein in Escherichia coli, purified to homogeneity and structurally
      analyzed. Recombinant M (i) forms non-covalently bound multimers with a Stoke's
      radius of 35 Angstroms estimated by size exclusion chromatography, (ii) consists
      of tetramers detected by analytical ultracentrifugation, and (iii) appears by
      electron microscopy studies as tetramers with the tendency to assemble into high
      molecular mass lattice-like complexes. The structural features suggest that BDV-M
      possesses a dominant driving force for virus particle formation.

PMID- 15862311
TI  - A novel neurotrophic role of secretory phospholipases A2 for cerebellar granule
      neurons.
AB  - Cultured cerebellar granule neurons (CGNs) require membrane depolarization or
      neurotrophic factors for their survival in vitro and undergo apoptosis when
      deprived of these survival-promoting stimuli. Here, we show that secretory
      phospholipases A(2)s (sPLA(2)s) rescue CGNs from apoptosis after potassium
      deprivation. The neurotrophic effect required the enzymatic activity of sPLA(2)s,
      since catalytically inactive mutants of sPLA(2)s failed to protect CGNs from
      apoptosis. Consistently, the ability of sPLA(2)s to protect CGNs from apoptosis
      correlated with the extent of sPLA(2)-induced arachidonic acid release from live
      CGNs. The survival-promoting effect of sPLA(2) was inhibited by depletion of
      extracellular Ca(2+) or by the presence of L-type Ca(2+) channel blocker
      nicardipine, suggesting that Ca(2+) influx occurs upon sPLA(2) treatment. Among
      the mammalian sPLA(2)s tested, only group X sPLA(2), but not group IB nor IIA
      sPLA(2)s, displayed neurotrophic activity. These results suggest a novel,
      unexpected neurotrophin-like role of sPLA(2) in the nervous system.

PMID- 15862312
TI  - Long CGG-repeat tracts are toxic to human cells: implications for carriers of
      Fragile X premutation alleles.
AB  - People with 59-200 CGG.CCG-repeats in the 5' UTR of one of their FMR1 genes are
      at risk for Fragile X tremor and ataxia syndrome. Females are also at risk for
      premature ovarian failure. These symptoms are thought to be due to the presence
      of the repeats at the DNA and/or RNA level. We show here that long transcribed
      but untranslated CGG-repeat tracts are toxic to human cells and alter the
      expression of a wide variety of different genes including caspase-8, CYFIP,
      Neurotensin and UBE3A.

PMID- 15862314
TI  - Purkinje-cell degeneration in prion protein-deficient mice is associated with a
      cerebellum-specific Doppel protein species signature.
AB  - PrP(c) (cellular prion protein) and Doppel are antagonizing proteins,
      respectively neuroprotective and neurotoxic. Evidence for Doppel neurotoxicity
      came from PrP(c)-deficient (Prnp(0/0)) mouse lines developing late onset Purkinje
      cell degeneration caused by Doppel overexpression in brain. To address the
      molecular underpinnings of this cell-type specificity, we generated Doppel N
      terminal-specific antibodies and started to examine the spatio-temporal
      expression of Doppel protein species in Ngsk Prnp(0/0) brain. Although Doppel
      overexpression is ubiquitous, Western analyses of normal and deglycosylated
      protein extracts revealed cerebellar patterns distinct from the rest of the
      brain, supporting the idea that neurotoxicity might be linked to a particular
      Doppel species pattern. Furthermore, our newly raised antibodies allowed the
      first Doppel immunohistochemical analyses in brain, showing a distribution in
      Prnp(0/0) cerebellum similar to PrP(c) in wild type.

PMID- 15862315
TI  - A hyaluronan synthase suppressor, 4-methylumbelliferone, inhibits liver
      metastasis of melanoma cells.
AB  - 4-Methylumbelliferone (MU) inhibits the cell surface hyaluronan (HA) formation,
      and that such inhibition results in suppression of adhesion and locomotion of
      cultured melanoma cells. Here, we examine the effect of MU on melanoma cell
      metastasis in vivo. MU-treated melanoma cells showed both decreased cell surface
      HA formation and suppression of liver metastasis after injection into the mice.
      Oral administration of MU to mice decreased tissue HA content. These HA knock
      down mice displayed suppressed liver metastasis. Thus, both cell surface HA of
      melanoma cells and recipient liver HA can promote liver metastasis, indicating
      that MU has potential as an anti-metastatic agent.

PMID- 15862316
TI  - Scallop DMT functions as a Ca2+ transporter.
AB  - We identified a DMT (divalent metal transporter) homologous protein that
      functions as a Ca(2+) transporter. Scallop DMT cDNA encodes a 539-amino-acid
      protein with 12 putative membrane-spanning domains and has a consensus transport
      motif in the fourth extracellular loop. Since its mRNA is significantly expressed
      in the gill and intestine, it is assumed that scallop DMT transports Ca(2+) from
      seawater by the gill and from food by the intestine. Scallop DMT lacks the iron
      responsive element commonly found in iron-regulatory proteins, suggesting that it
      is free of the post-transcriptional regulation from intracellular Fe(2+)
      concentration. Scallop DMT distinctly functions as a Ca(2+) transporter unlike
      other DMTs, however, it also transports Fe(2+) and Cd(2+) similar to them.

PMID- 15862317
TI  - Morphological and phenotypical characterization of human endothelial progenitor
      cells in an early stage of differentiation.
AB  - The exact phenotype and lineage of endothelial progenitor cells (EPCs) are still
      a matter of debate and different expansion protocols are used to obtain them. In
      this study, EPC expansion from peripheral blood mononuclear cells was analyzed
      within the first week of culture. Both the adherent and suspended cells, of which
      the latter usually discarded, were considered. We provide, for the first time, a
      systematic study of EPC phenotype and functional features within the first 3 days
      of culture. Moreover, within the 2nd day, both cellular fractions displayed a
      significant increase in endothelial marker expression which correlated with EPC
      properties.

PMID- 15862318
TI  - cda1+, encoding chitin deacetylase is required for proper spore formation in
      Schizosaccharomyces pombe.
AB  - In Schizosaccharomyces pombe, a major role of chitin is to build up a complete
      spore. Here, we analyzed the cda1(+) gene (SPAC19G12.03), which encodes a protein
      homologous to chitin deacetylases, to know whether it is required for spore
      formation in S. pombe. The homothallic Deltacda1 strain constructed by homologous
      recombination was found to form a little amount of abnormal spores that contained
      one, two, or three asci, similar to (but not as strong as) the phenotype observed
      in a deletion mutant of chs1 encoding chitin synthase 1. This phenotype is
      reversed by expression of S. cerevisiae chitin deacetylase CDA1 or CDA2,
      suggesting that cda1 encodes a chitin deacetylase. To support the role of Cda1 in
      sporulation, the timing of expression of cda1(+) mRNA increased during
      sporulation process. We also found that the Cda1 protein self-associated when its
      binding was tested both by two-hybrid system and immunoprecipitation. Thus, these
      data indicated that cda1(+) is required for proper spore formation in S. pombe.

PMID- 15862319
TI  - Substrate specificity and preference of Delta6-desaturase of Mucor rouxii.
AB  - The Delta(6)-fatty acid desaturase is a key enzyme in the synthesis of an
      important fatty acid, gamma-linolenic acid. We have characterized, by
      heterologous expression in Saccharomyces cerevisiae, substrate specificity and
      preference of Delta(6)-desaturase of Mucor rouxii. Fatty acid supplementation was
      carried out based on the predicted enzyme topology, fatty acid phenotype and the
      corresponding metabolic pathway in M. rouxii. The enzyme has a broad substrate
      specificity as based on C15-C18. The result also supported classification of the
      M. rouxii Delta(6)-desaturase into a front-end desaturase. Interestingly, a
      relatively rare activity based on odd acyl chains and not described previously in
      other eukaryotic Delta(6)-desaturases was also observed.

PMID- 15862313
TI  - Analysis of expressed sequence tags from oil palm (Elaeis guineensis).
AB  - This is the first report of a systematic study of genes expressed by means of
      expressed sequence tag (EST) analysis in oil palm, a species of the Arecales
      order, a phylogenetically key clade of monocotyledons that is not widely
      represented in the sequence databases. Five different cDNA libraries were
      generated from male and female inflorescences, shoot apices and zygotic embryos
      and unidirectional systematic sequencing was performed. A total of 2411 valid EST
      sequences were thus obtained. Cluster analysis enabled the identification of 209
      groups of related sequences and 1874 singletons. Putative functions were assigned
      to 1252 of the set of 2083 non-redundant ESTs obtained. The EST database
      described here is a first step towards gene discovery and cDNA array-based
      expression analysis in oil palm.

PMID- 15862320
TI  - Operational strategies for an activated sludge process in conjunction with ozone
      oxidation for zero excess sludge production during winter season.
AB  - A pilot-scale activated sludge system coupled with sludge ozonation process was
      operated for 112 days of a winter season without excess sludge wasting. The
      concept of this process is that the excess sludge produced is first disintegrated
      by ozone oxidation and then recirculated to a bioreactor in order to mineralize
      the particulate and soluble organic compounds. The basis of operation was to
      determine either the optimal amount of sludge in kg SS ozonated each day (SO) or
      the optimal ozonation frequency under the variable influent chemical oxygen
      demand (COD) loading and temperature conditions, since the ozone supply consumes
      costly energy. The optimal SO was obtained using the theoretically estimated
      sludge production rate (SP) and experimentally obtained ozonation frequency (n).
      While the SP was mainly subject to the COD loadings, sludge concentration was
      affected by the temperature changes in winter season. The optimal n was observed
      between 2.5 and 2.7 at around 15 degrees C, but it was doubled at 10 degrees C.
      Mixed liquor suspended solids (MLSS) concentration was leveled off at around 5000
      mg/L in bioreactor at 15 degrees C, but the volatile fraction of MLSS was fixed
      around 0.7 indicating that there was no significant inorganic accumulation.
      Suspended solids (SS) and soluble COD in effluents kept always a satisfactory
      level of 10 and 15 mg/L with sufficient biodegradation. It was recommended to
      apply a dynamic SO under variable influent COD loadings and temperature
      conditions to the activated sludge system without excess sludge production for
      saving energy as well as system stabilization.

PMID- 15862321
TI  - Monitoring aerobic sludge digestion by online scanning fluorometry.
AB  - With sludge samples from two wastewater treatment plants, batch experiments of
      aerobic sludge digestion were conducted under different dissolved oxygen (DO) and
      solids concentrations. A fluorometer capable of online excitation and emission
      scanning was used to monitor the digestion process. Three major fluorescence
      peaks were observed. The peak at excitation/emission maxima of 290/350 nm was
      attributed to the fluorescence of proteinaceous materials in the sludge, with
      tryptophan residues being the primary contributor. The sources for the other two
      peaks (at 370/430 nm and 430/510 nm) remain unknown. The well-known biological
      fluorescence from reduced nicotinamide adenine dinucleotides (NADH and NADPH), at
      excitation/emission maxima of 340/460 nm, was found very weak in the aerobic
      digestion systems studied. It was buried under the broad peak at 370/430 nm and
      was detectable only in the early stage of the experiment that had the highest
      solids loading (at 4.8%) and was operated under low DO (0.2-1.0mg/L) conditions.
      On the other hand, the profile of the protein fluorescence (PF) correlated well
      with that of the volatile solids (VS) reduction in all the experiments. A semi
      empirical exponential decay function was developed, which described well the
      profiles of both normalized VS and normalized PF. The feasibility of following
      the real-time performance of aerobic sludge digestion by monitoring PF was
      clearly demonstrated.

PMID- 15862322
TI  - Organic markers in the lipidic fraction of sewage sludges.
AB  - The lipidic organic fraction of 48 sewage sludges that originated from food
      processing, paper-mill and domestic (urban, small urban, and rural) wastewater
      treatment plants of the Lorraine region (Northeast of France) was characterised
      by gas chromatography coupled with mass spectrometer (GC-MS). This study enables
      us to define an average organic composition typical of each group of sewage
      sludges. Linear alkyl benzenes (LABs) are only present in domestic sludges,
      sterols in food-processing and domestic sludges. Paper-mill sludges are
      characterised by the specific distribution of n-alkanes. Besides, all the
      domestic sludges, whatever the size of the wastewater catchment, are
      characterised by the same distribution of polar compounds. Differences can be
      evidenced in the distribution of the aliphatic compounds of some domestic sewage
      sludges and are attributed to the important contribution of petroleum products in
      their sewer system. Moreover, this study highlights the correlation between
      abundance of polycyclic aromatic hydrocarbons (PAHs) in the aromatic fraction of
      some sewage sludges and a distribution of n-alkanes characteristic of heavy
      petroleum products into the corresponding aliphatic fraction. This might be a
      clue for the determination of punctual sources of PAHs.

PMID- 15862323
TI  - Combined influence of membrane surface properties and feed water qualities on
      RO/NF mass transfer, a pilot study.
AB  - The impact of membrane surface characteristics and NOM on membrane performance
      has been investigated for varying pretreatment and membranes in a field study.
      Surface charge, hydrophobicity and roughness varied significantly among the four
      membranes used in the study. The membranes were tested in parallel following two
      different pretreatment processes, an enhanced Zenon ultrafiltration process (ZN)
      and a compact CSF process (Superpulsator (SP)) prior to RO membrane treatment for
      a total of eight integrated membrane systems. All membrane systems were exposed
      to the similar temperature, recovery and flux as well as chemical dosage. The
      membrane feed water qualities were statistically equivalent following ZN
      pretreatment and SP pretreatment except for NOM and SUVA. Membrane surface
      characteristics, NOM and SUVA measurements were used to describe mass transfer in
      a low-pressure RO integrated membrane system. Solute and water mass transfer
      coefficients (MTCs) were investigated for dependence on membrane surface
      properties and NOM mass loading. Inorganic MTCs were accurately described by a
      Gaussian distribution curve. Water productivity decreased with NOM loading and
      increased with contact angle and roughness. The negative effects of NOM loading
      on productivity were reduced as the negative charge on the membrane surface
      increased. Inorganic MTCs were also correlated to surface hydrophobicity and
      surface roughness. The permeability change of identical membranes was related to
      NOM loading, hydrophobicity and roughness. Organic fouling as measured by water,
      organic and inorganic mass transfer was less for membranes with higher
      hydrophilicity and roughness.

PMID- 15862324
TI  - Phosphorus adsorption on natural sediments: modeling and effects of pH and
      sediment composition.
AB  - The classic Langmuir isotherm equation was modified to describe phosphorus (P)
      adsorption on P-polluted sediments. The P adsorption characteristics of six
      sediment samples from Chinese Taihu Lake were studied by short-term isotherm
      batch experiments and related to sediment composition. The maximum P adsorption
      capacities (PAC) and P-binding energy constant (k) were obtained by nonlinearly
      fitting sorption data using the modified Langmuir isotherm model. Native adsorbed
      exchangeable phosphorus (NAP), the zero equilibrium P concentration value
      (EPC(0)), and partitioning coefficients (K(p)) were subsequently calculated by
      corresponding formulae. K(p) and PAC were linearly related to the contents of
      active Fe and Al in sediments by least squares regression analyses (R(2)
      approximately 0.9 for both). The effect of pH in a wide range on adsorption
      process was investigated and H2PO4- was presumed to be the preferential sorption
      species in overall sorption process. The fact that the amount of P sorbed and
      zeta potential of sediment particles have no necessary relationship reveals that
      a strong contribution to the P binding still comes from a ligand-exchange process
      on the Me-OH(2+) and Me-OH sites rather than electrostatic attraction. In
      addition, the influence of oxidation-reduction potential (ORP) was investigated
      and discussed and the dual nature of sediments as a pool or source of P in
      natural waters was evaluated in site T1-T4.

PMID- 15862325
TI  - Filter pore size selection for characterizing dissolved organic carbon and
      trihalomethane precursors from soils.
AB  - Filters with a pore size of 0.45 microm have been arbitrarily used for isolating
      dissolved organic carbon (DOC) in natural waters. This operationally defined DOC
      fraction often contains heterogeneous organic carbon compounds that may lead to
      inconsistent results when evaluating trihalomethane formation potential (THMFP).
      A finer pore size filter provides more homogeneous DOC properties and enables a
      better characterization of organic matter. In this study, we examined the effects
      of filter pore size (1.2, 0.45, 0.1 and 0.025 microm) on characterizing total
      organic carbon, ultra-violet absorbance at 254 nm (UV(254)) and THMFP of water
      extracts from a mineral and organic soil in the Sacramento-San Joaquin Delta,
      California. Results showed that the majority of water extractable organic carbon
      (WEOC) from these soils was smaller than 0.025 microm, 85% and 57% in organic and
      mineral soils, respectively. A high proportion of colloidal organic carbon (COC)
      in mineral soil extracts caused water turbidity and resulted in an abnormally
      high UV(254) in 1.2 and 0.45 microm filtrates. The reactivity of organic carbon
      fractions in forming THM was similar for the two soils, except that COC from the
      mineral soil was about half that of others. To obtain a more homogeneous solution
      for characterizing THM precursors, we recommend a 0.1 microm or smaller pore-size
      filter, especially for samples with high colloid concentrations.

PMID- 15862326
TI  - Bench-scale testing of a magnetic ion exchange resin for removal of disinfection
      by-product precursors.
AB  - The objective of this research was to compare enhanced coagulation with anion
      exchange for removal of disinfection by-product (DBP) precursors (i.e. natural
      organic matter (NOM) and bromide). Treatment with a magnetic ion exchange resin
      (MIEX((R))) was the primary focus of this study. Raw waters from four utilities
      in California were evaluated. The waters had low turbidity, low to moderate
      organic carbon concentrations, a wide range of alkalinities, and moderate to high
      bromide ion concentrations. The treated waters were compared based on removal of
      ultraviolet (UV) absorbance, dissolved organic carbon (DOC), trihalomethane
      formation potential (THMFP), and haloacetic acid formation potential (HAAFP). The
      results indicated that treatment with MIEX is more effective than coagulation at
      removing UV-absorbing substances and DOC. Treatment with MIEX and treatment with
      MIEX followed by coagulation yielded similar results, suggesting that coagulation
      of MIEX-treated water does not provide additional removal of organic carbon. MIEX
      treatment reduced the THMFP and HAAFP in all waters, and did so to a greater
      extent than coagulation. Treatment with MIEX was most effective in raw waters
      having a high specific UV absorbance and a low anionic strength. Following MIEX
      treatment, subsequent chlorination resulted in a shift to the more brominated THM
      and HAA species as compared to chlorination of the raw water. MIEX also removed
      bromide to varying degrees, depending on the raw water alkalinity and initial
      bromide ion concentration.

PMID- 15862327
TI  - Distribution of indicator bacteria in Canyon Lake, California.
AB  - The spatial and temporal distributions of indicator bacteria in a small, multiple
      use source drinking water reservoir in Southern California, USA were quantified
      over the period August 2001-July 2002. High levels of total and fecal coliform
      bacteria were present in Canyon Lake (annual geometric mean concentrations+/-SEM
      of 3.93+/-0.02 and 3.02+/-0.03 log cfu/100mL, respectively), while comparatively
      low levels of enterococci and E. coli were found (1.16+/-0.02 log cfu/100mL and
      0.30+/-0.03 log MPN/100mL, respectively). As a result, these different indicator
      bacteria yielded quite divergent indices of water quality, with 72.1% of all
      surface samples (n=294) exceeding the USEPA single-sample limit of 400 cfu/100mL
      fecal coliform bacteria, while none (0%) of the samples exceeded the single
      sample limit for E. coli (n=194). Regression analyses found a positive
      correlation between total and fecal coliform bacteria (R=0.50, significant at
      p<0.001) and between enterococci and E. coli (R=0.51, significant at p<0.001),
      but no correlation or inverse correlations were found between coliform
      concentrations and enterococci and E. coli levels. External sources responsible
      for the high total and fecal coliform bacteria were not identified, although
      laboratory studies demonstrated growth of the coliform bacteria in lake water
      samples. Enterococci and E. coli were not observed to grow, however. Bacteria
      concentrations varied relatively little laterally across the lake, although
      strong vertical gradients in fecal coliform and enterococcus bacteria
      concentrations were present during summer stratification, with concentrations
      about 10x higher above the thermocline when compared with surface concentrations.
      In contrast, total bacteria, total virus and total coliform bacteria levels were
      unchanged with depth. Seasonal trends in bacteria concentrations were also
      present. This study shows that the choice of indicator bacteria and sampling
      depth can both strongly affect the apparent microbial water quality of a lake or
      reservoir.

PMID- 15862328
TI  - Separate estimation of adsorption and degradation of pharmaceutical substances
      and estrogens in the activated sludge process.
AB  - The removal of three estrogens such as 17beta-estradiol, two endocrine disruptors
      like bisphenol A, and 10 pharmaceutical substances like ibuprofen (IBP) by
      activated sludge was experimentally examined. The contribution of adsorption and
      degradation to the overall removal was estimated separately and successfully. At
      the neutral pH condition, the target pharmaceutical substances showed little
      tendency of adsorption to the sludge and their water-sludge partition
      coefficients were lower than those of the target estrogens. On the other hand,
      the increasing tendency of adsorption was observed in the lower pH condition. A
      linear relationship between the log of the partitioning coefficient and logK(ow)
      was observed when pH was lowered to keep the pharmaceuticals neutral solutes. The
      acidic operational condition was preferable for the removal of acidic
      pharmaceutical substances because the limiting stage for the removal was not
      biodegradation but the transfer of substances from the water phase to the sludge
      phase.

PMID- 15862329
TI  - Sequential polymer dosing for effective dewatering of ATAD sludges.
AB  - Dewatering problems associated with the sludge from autothermal thermophilic
      aerobic digestion (ATAD) of sludge, result in large chemical conditioning costs
      for effective dewatering. A variety of chemical conditioners were used to improve
      dewatering, but none of them were able to dewater the sludge as desired at
      acceptable conditioning doses. It was found that during the digestion process,
      chemical precipitation of divalent cations occurred. Some of the ATAD sludge
      colloids were found to have a positive zeta potential and these were thought to
      be the precipitated divalent cations. Sequential polymer dosing using either iron
      or cationic polymer, followed by anionic polymer, was found to improve
      dewatering. The use of anionic polymer is essential and allows the use of smaller
      amounts of iron or cationic polymer for effective dewatering. The use of the less
      expensive anionic polymer along with cationic polymers has the potential to make
      the use of the ATAD process more economical.

PMID- 15862330
TI  - Modeling biofilm and floc diffusion processes based on analytical solution of
      reaction-diffusion equations.
AB  - Biofilm modeling is often considered as a complex mathematical subject. This
      paper evaluates simple equations to describe the basic processes in a biofilm
      system with the main aim to show several interesting applications. To avoid
      mathematical complexity the simulations are carried out in a simple spreadsheet.
      Frequently, only the solution for zero-order reaction kinetics of the reaction
      diffusion equation is used (better known as half-order kinetics). A weighted
      average of the analytical solutions for zero- and first-order reactions is
      proposed as basic and useful model to describe steady-state (in biofilm
      composition) biofilm reactors. This approach is compared with several modeling
      approaches, such as the simple solution for zero-order reaction and more complex
      ones (i) direct numerical solution for the diffusion equations, (ii) 1-D AQUASIM
      and (iii) 2-D modeling. The systems evaluated are single and multiple species
      biofilms. It is shown that for describing conversions in biofilm reactors, the
      zero-order solution is generally sufficient; however, for design purposes large
      deviations of the correct solution can occur. Additionally, the role of diffusion
      in flocculated and granular sludge systems is discussed. The relation between the
      measured (apparent) substrate affinity constant and diffusion processes is
      outlined.

PMID- 15862331
TI  - Adsorption mechanism of palladium by redox within condensed-tannin gel.
AB  - Condensed-tannin gel particles with polyhydroxyphenyl groups were synthesized as
      the adsorbent for the new recovery system of palladium (Pd), which was simple and
      generated little secondary waste in comparison with the conventional recovery
      processes. The properties of condensed-tannin gel particles for the Pd adsorption
      were examined in PdCl2 aqueous solution and it was found that Pd(II) was adsorbed
      onto the tannin gel particles as a reduced metallic Pd through redox reaction
      mechanism: chloropalladium(II) species were reduced to Pd(0), while hydroxyl
      groups of condensed-tannin gel were oxidized during the adsorption. Additionally,
      it was observed that Pd(II) species containing fewer Cl, such as PdCl2(H2O)2 and
      PdCl(H2O)3+, were more favorable for the adsorption than PdCl3(H2O)- and PdCl4(2
      ). By utilizing such characteristics of tannin gel particles, it is expected that
      they can be applied to recover Pd efficiently and simply with low cost.

PMID- 15862332
TI  - Monitoring of trifluoroacetic acid concentration in environmental waters in
      China.
AB  - It is critically important and extremely meaningful to determine the
      concentration of TFA in the environmental water in China. This will create
      background reference for the effects of analyzing the extensive employment of the
      substitutes to CFCs in China. In this paper a set of analytical methods was
      described for use in monitoring of trifluoroacetic acid (TFA) concentration of
      environmental waters including collecting, pre-treatment measures, preserving,
      concentrating and derivatization of samples from different kinds of environmental
      waters. The GC with electrical capture detector (ECD) and headspace auto sampler
      were used in the analysis. The lowest detection limit of the instrument is 0.0004
      ng methyl trifluoroacetic acid (MTFA), and the lowest detected concentration with
      the method is 3.0 ng/ml TFA. TFA collected in various environmental water samples
      (including rainfall, inland surface water, ground water, and waste water) from
      nine provinces and autonomous regions in China have been determined by applying
      the analytical methods created and defined in this work. The results indicate
      that the concentrations of TFA in nine rainfalls and three snowfalls through the
      period from 2000 to 2001 ranged from 25 to 220 ng/l, the TFA concentration in the
      inland surface water samples ranged from 4.7 to 221 ng/l, the concentration of
      TFA in groundwater samples collected in Beijing was 10 ng/l, and the TFA
      concentration in coastal water samples ranged from 4.2 to 190.1 ng/l.

PMID- 15862333
TI  - Preparation and application of TiO2 photocatalytic sensor for chemical oxygen
      demand determination in water research.
AB  - In this work, a TiO(2) photocatalytic sensor was prepared and utilized into flow
      injection analysis (FIA) for chemical oxygen demand (COD) determination. With a
      positive bias potential of 0.4V (vs. Ag/AgCl) applied to the sensor and a 12-W
      quartz UV lamp illuminating it, photocurrent, due to the charge transfer at the
      interface of TiO(2) sensor and the passing solution, was recorded and its change
      (deltaI(Photo)) caused by the detected sample was calculated to characterize the
      COD value of the sample. Under the optimizing conditions, the sensor responded
      linearly to the COD of D-glucose solution in the range of 0.5-235 mg/L, with a
      linear correlation coefficient of 0.9998. Its application in artificial
      wastewater analysis has achieved results in good agreement with those from the
      conventional dichromate method; meanwhile, the process requires no hypertoxic
      reagents and less analysis time, suggesting that it would be another appropriate
      method for COD determination in water assessment.

PMID- 15862334
TI  - Adsorption-desorption characteristics of phenol and reactive dyes from aqueous
      solution on mesoporous activated carbon prepared from waste tires.
AB  - Liquid-phase adsorption-desorption characteristics and ethanol regeneration
      efficiency of an activated carbon prepared from waste tires and a commercial
      activated carbon were investigated. Water vapor adsorption experiments reveal
      that both activated carbons showed hydrophobic surface characteristics.
      Adsorption experiments reveal that the prepared activated carbon possessed
      comparable phenol adsorption capacity as the commercial one but clearly larger
      adsorption capacity of two reactive dyes, Black 5 and Red 31. It was ascertained
      that the prepared activated carbon exhibited less irreversible adsorption of
      phenol and the two dyes than its commercial counterpart. Moreover, ethanol
      regeneration efficiency of the prepared AC saturated with either dye was higher
      than that of the commercial AC. Because of its superior liquid-phase adsorption
      desorption characteristics as well as higher ethanol regeneration efficiency, the
      prepared activated carbon is more suitable for wastewater treatment, especially
      for adsorbing similarly bulky adsorbates.

PMID- 15862335
TI  - Indicator bacteria at five swimming beaches-analysis using random forests.
AB  - "Random forests," an extension of tree regression, provide a relatively new
      technique for exploring relationships of a response variable like the density of
      indicator bacteria in water to numerous potential explanatory variables. We used
      this tool to study relationships of indicator density at five beaches to numerous
      other variables and found that day of the week, indicator density 24h earlier,
      water depth at the sampling point, cloud cover, and others were related to
      density at one or more of the beaches. Using data from the first 52 days of
      measurement allowed predicting indicator densities in the following 10 days to
      order of magnitude at some of the beaches. Our analyses served to demonstrate the
      potential usefulness of this analytic tool for large data sets with many
      variables.

PMID- 15862336
TI  - Effect of plants and filter materials on bacteria removal in pilot-scale
      constructed wetlands.
AB  - Due to the lack of testing units or appropriate experimental approaches, only
      little is known about the removal of bacteria in constructed wetlands. However,
      improved performance in terms of water sanitation requires a detailed
      understanding of the ongoing processes. Therefore, we analyzed the microbial
      diversity and the survival of Enterobacteriaceae in six pilot-scale constructed
      wetland systems treating domestic wastewater: two vertical sand filters, two
      vertical expanded clay filters and two horizontal sand filters (each planted and
      unplanted). Samples were taken from the in- and outflow, from the rhizosphere,
      and from the bulk soil at various depths. Colony-forming units of heterotrophic
      bacteria and coliforms were analyzed and the removal of bacteria between the in-
      and outflow was determined to within 1.5-2.5 orders of magnitude. To access the
      taxon-specific biodiversity of potential pathogens in the filters and to reduce
      the complexity of the analysis, specific primers for Enterobacteriaceae were
      developed. While performing PCR-SSCP analyses, a pronounced decrease in diversity
      from the inflow to the outflow of treated wastewater was observed. No differences
      were observed between the bulk soil of planted and unplanted vertical filters.
      Some bands appeared in the rhizosphere that were not present in the bulk soil,
      indicating the development of specific communities stimulated by the plants. The
      fingerprinting of the rhizosphere of plants grown on sand or expanded clay
      exhibited many differences, which show that different microbial communities exist
      depending on the soil type of the filters. The use of the taxon-specific primers
      enabled us to evaluate the fate of the Enterobacteriaceae entering the wetlands
      and to localize harboring in the rhizosphere. The most abundant bands of the
      profiles were sequenced: Pantoea agglomerans was found in nearly all samples from
      the soil but not in the effluent, whereas Citrobacter sp. could not be removed by
      the horizontal unplanted sand and vertical planted expanded clay filters. These
      results show that the community in wetland system is strongly influenced by the
      filtration process, the filter material and the plants.

PMID- 15862337
TI  - Spark-induced consolidation of biological sludge.
AB  - Subjecting a suspension of biological sludge to underwater sparks (3kV, 50kA)
      leads to its consolidation, decreases the charge density on the solids, and
      increases its settling rate. The cake solids increase, but by only one percentage
      point. High-speed video images show that the spark generates a steam bubble. The
      dynamics of bubble growth could be estimated through the Rayleigh model. The
      bubble collapses into an acoustic field, which then agglomerates the particles.
      Sparking does not affect the settling rate of an aqueous slurry of softwood pulp
      because the fibrous particles are too large to be aggregated by an acoustic
      pulse.

PMID- 15862338
TI  - Predicting oxygen transfer of fine bubble diffused aeration systems--model issued
      from dimensional analysis.
AB  - The standard oxygenation performances of fine bubble diffused aeration systems in
      clean water, measured in 12 cylindrical tanks (water depth from 2.4 to 6.1m),
      were analysed using dimensional analysis. A relationship was established to
      estimate the scale-up factor for oxygen transfer, the transfer number (N(T)) The
      transfer number, which is written as a function of the oxygen transfer
      coefficient (k(L)a(20)), the gas superficial velocity (U(G)), the kinematic
      viscosity of water (nu) and the acceleration due to gravity (g), has the same
      physical meaning as the specific oxygen transfer efficiency. N(T) only depends on
      the geometry of the tank/aeration system [the total surface of the perforated
      membrane (S(p)), the surface of the tank (S) or its diameter (D), the total
      surface of the zones covered by the diffusers ("aerated area", S(a)) and the
      submergence of the diffusers (h)]. This analysis allowed to better describe the
      mass transfer in cylindrical tanks. Within the range of the parameters
      considered, the oxygen transfer coefficient (k(L)a(20)) is an increasing linear
      function of the air flow rate. For a given air flow rate and a given tank surface
      area, k(L)a(20) decreases with the water depth (submergence of the diffusers).
      For a given water depth, k(L)a(20) increases with the number of diffusers, and,
      for an equal number of diffusers, with the total area of the zones covered by the
      diffusers. The latter result evidences the superiority of the total floor
      coverage over an arrangement whereby the diffusers are placed on separate grids.
      The specific standard oxygen transfer efficiency is independent of the air flow
      rate and the water depth, the drop in the k(L)a(20) being offset by the increase
      of the saturation concentration. For a given tank area, the impact of the total
      surface of the perforated membrane (S(p)) and of the aerated area (S(a)) is the
      same as on the oxygen transfer coefficient.

PMID- 15862339
TI  - Non-ionic surfactant flushing of pentachlorophenol from NAPL-contaminated soil.
AB  - Column studies were conducted to assess the suitability of a non-ionic surfactant
      Tergitol NP-10 (TNP10) for washing pentachlorophenol (PCP) from soil and non
      aqueous phase liquids (NAPLs). Flushing of 50 and 200 pore volumes of 5 g/L TNP10
      was required to exhaust the surfactant sorption capacity of the soil and soil
      plus NAPL, respectively. The sorption of surfactant to the soil in the columns
      was four times greater than the quantity previously observed in batch tests.
      Flushing with 5 g/L TNP10 removed 71-79% of the 200mg/kg soil-sorbed PCP after
      160 pore volumes compared to 0.7-2% PCP removal without surfactant. In columns
      additionally containing 0.2% and 0.4% PCP-contaminated heavy oil NAPL, the PCP
      removal efficiency after flushing 200 pore volumes of 5g/L TNP10 was nearly 100%.
      Therefore, removal of the PCP was more efficient in the NAPL-containing columns,
      potentially due to competition of the NAPL for PCP sorption sites. Rate-limited
      desorption of PCP and TNP10 likely occurred.

PMID- 15862340
TI  - Relative survival of Escherichia coli and Salmonella typhimurium in a tropical
      estuary.
AB  - Microcosm studies have been carried out to find out the relative survival of
      Escherichia coli and Salmonella typhimurium in a tropical estuary. Survival has
      been assessed in relation to the important self-purifying parameters such as
      biotic factors contained in the estuarine water, toxicity due to the dissolved
      organic and antibiotic substances in the water and the sunlight. The results
      revealed that sunlight is the most important inactivating factor on the survival
      of E. coli and S. typhimurium in the estuarine water. While the biological
      factors contained in the estuarine water such as protozoans and bacteriophages
      also exerted considerable inactivation of these organisms, the composition of the
      water with all its dissolved organic and inorganic substances was not damaging to
      the test organisms. Results also indicated better survival capacity of E. coli
      cells under all test conditions when compared to S. typhimurium.

PMID- 15862341
TI  - Relative vs. absolute statistical analysis of compositions: a comparative study
      of surface waters of a Mediterranean river.
AB  - Most hydrogeological research includes some sort of statistical study, which is
      generally conducted on the raw measures of chemical variables, though there are
      several theoretical and practical studies warning against this practice.
      Arguments refer mainly to the positive character of this type of data, and to the
      fact that they carry only information about the relative abundance of each
      component on the whole, what makes techniques based on correlation, like the
      widely used Principal Component Analysis (PCA), loose their meaning. The solution
      proposed by Aitchison (1982, Journal of the Royal Statistical Society, Series B
      44(2), 139-177)-based on working with log-ratios of observations-is equivalent to
      define a new distance between compositions and to adapt usual statistical
      techniques to it. To illustrate its effect, our study compares the performance of
      the biplot-a PCA graphical technique-according to the usual Euclidean and to the
      Aitchison distance. The study is conducted on a set of 14 molarities measured
      monthly through the years 1997-1999 at 30 different stations along the Llobregat
      River and its tributaries (Barcelona, NE Spain). Ordinary analysis, implicitly
      based on an Euclidean distance, presents some deficiencies, mainly because it
      only captures major ion variations and the inferred relationship between them
      actually depends on other non-relevant variables, such as water mass. An analysis
      based on compositional distances captures variations of all the ions; it is
      robust against the inclusion of non-relevant variables in the analysis; and it
      offers a way to build factors expressed as equilibrium equations. In our case,
      two promising factors are extracted, showing the different anthropogenic and
      geological pollution sources of the rivers.

PMID- 15862342
TI  - A fuzzy index model for trophic status evaluation of reservoir waters.
AB  - An index model for quality evaluation based on the formula of similarity
      membership functions in the fuzzy c-means (FCM) clustering algorithm is proposed.
      Summing up the weighted similarity degrees between an observation and designed
      specific quality-ordered levels develops an alternative overall index. Stretching
      the values of the controlling parameters in the formula of the similarity
      membership functions causes diverse patterns of overall index models. Applying
      this proposed fuzzy index model to the trophic evaluation of reservoir waters is
      studied to demonstrate the practical application of this index. Every measurement
      of the variables is standardized by the membership function of quality evaluation
      on the interval [0,1], referring to the trophic status clarified in the Carlson
      Trophic State Index. The sensitivity analyses are studied both in the proposed
      index system and the Carlson Trophic State Index. Besides, a case study of the
      trophic status evaluation of the Feitsui Reservoir from 1987 to 2003 is presented
      to demonstrate the feasibility of applying the proposed evaluation model.

PMID- 15862343
TI  - Calcium sparks in skeletal muscle fibers.
AB  - Ca(2+) sparks monitor transient local releases of Ca(2+) from the sarcoplasmic
      reticulum (SR) into the myoplasm. The release takes place through ryanodine
      receptors (RYRs), the Ca(2+)-release channels of the SR. In intact fibers from
      frog skeletal muscle, the temporal and spatial properties of voltage-activated
      Ca(2+) sparks are well simulated by a model that assumes that the Ca(2+) flux
      underlying a spark is 2.5 pA (units of Ca(2+) current) for 4.6 ms (18 degrees C).
      This flux amplitude suggests that 1-5 active RYRs participate in the generation
      of a typical voltage-activated spark under physiological conditions. A major goal
      of future experiments is to estimate this number more precisely and, if it is two
      or more, to investigate the communication mechanism that allows multiple RYRs to
      be co-activated in a rapid but self-limited fashion.

PMID- 15862344
TI  - Interleukin-8 primes oxidative burst in neutrophil-like HL-60 through changes in
      cytosolic calcium.
AB  - In response to a variety of stimuli, neutrophils release large amount of reactive
      oxygen species (ROS) generated by NADPH oxidase. This process known as the
      respiratory burst is dependent on cytosolic free calcium concentration
      ([Ca(2+)](i)). Proinflammatory cytokines such as interleukin-8 (IL-8) may
      modulate ROS generation through a priming phenomenon. The aim of this study was
      to determine the effect of human IL-8 on ROS production in neutrophil-like
      dimethylsulfoxide-differentiated HL-60 cells (not equalHL-60 cells) and further
      to examine the role of Ca(2+) mobilization during the priming. IL-8 at 10 nM
      induced no ROS production but a [Ca(2+)](i) rise (254 +/- 36 nM). IL-8 induced a
      strongly enhanced (2 fold) ROS release during stimulation with 1 microM of N
      formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLF). This potentiation of ROS
      production is dependent of extracellular Ca(2+) (17.0+/-4.5 arbitrary units
      (A.U.) in the absence of Ca(2+) versus 56.6 +/- 3.9 A.U. in the presence of 1.25
      mM of Ca(2+)). Also, IL-8 enhanced fMLF-stimulated increase in [Ca(2+)](i) (375
      +/- 35 versus 245 +/- 21 nM, 0.1 microM of fMLF). IL-8 had no effect on not
      equalHL-60 cells in response to 1 microM of thapsigargin (472 +/- 66 versus 470
      +/- 60 nM). In conclusion, Ca(2+) influx is necessary for a full induction of
      neutrophil priming by IL-8.

PMID- 15862345
TI  - Dominant affectors in the calmodulin network shape the time courses of target
      responses in the cell.
AB  - In endothelial cells nitric oxide synthase is a dominant affector in the
      calmodulin network by virtue of its ability to bind a significant fraction of
      limiting intracellular calmodulin. We have investigated how this affector
      function influences the kinetics of calmodulin-dependent signaling in cells co
      expressing the synthase and a fluorescent calmodulin target analog similar in its
      interactions with calmodulin to myosin light chain kinase. The synthase binds
      (Ca(2+))(4)-calmodulin with a K(d) value of approximately 0.2 nM and an
      association rate constant of approximately 1.5 x 10(5) M(-1) s(-1). These values
      are, respectively, 10- and 100-fold smaller than the corresponding values for the
      analog. Thus, when Ca(2+) is added to a mixture of calmodulin, target analog and
      synthase in vitro a large fluorescence transient with a relaxation time of
      approximately 600 s is observed as (Ca(2+))(4)-calmodulin is rapidly bound to the
      analog and then slowly captured by the higher affinity synthase. A rapid increase
      in the free Ca(2+) concentration elicits similar transient analog responses in
      cells expressing the cytoplasmic target analog and either a wild-type membrane
      bound or mutant cytoplasmic synthase. Transient responses are not observed in
      cells co-expressing the fluorescent analog and a mutant T497D synthase unable to
      bind calmodulin. These results demonstrate that dominant affectors in the
      calmodulin network shape both the magnitudes and time courses of target responses
      in the cell.

PMID- 15862346
TI  - Calcium dynamics in catecholamine-containing secretory vesicles.
AB  - We have used an aequorin chimera targeted to the membrane of the secretory
      granules to monitor the free [Ca(2+)] inside them in neurosecretory PC12 cells.
      More than 95% of the probe was located in a compartment with an homogeneous
      [Ca(2+)] around 40 microM. Cell stimulation with either ATP, caffeine or high
      K(+) depolarization increased cytosolic [Ca(2+)] and decreased secretory granule
      [Ca(2+)] ([Ca(2+)](SG)). Inositol-(1,4,5)-trisphosphate, cyclic ADP ribose and
      nicotinic acid adenine dinucleotide phosphate were all ineffective to release
      Ca(2+) from the granules. Changes in cytosolic [Na(+)] (0-140 mM) or [Ca(2+)] (0
      10 microM) did not modify either ([Ca(2+)](SG)). Instead, [Ca(2+)](SG) was highly
      sensitive to changes in the pH gradient between the cytosol and the granules.
      Both carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) and nigericin,
      as well as cytosolic acidification, reversibly decreased [Ca(2+)](SG), while
      cytosolic alcalinization reversibly increased [Ca(2+)](SG). These results are
      consistent with the operation of a H(+)/Ca(2+) antiporter in the vesicular
      membrane. This antiporter could also mediate the effects of ATP, caffeine and
      high-K(+) on [Ca(2+)](SG), because all of them induced a transient cytosolic
      acidification. The FCCP-induced decrease in [Ca(2+)](SG) was reversible in 10-15
      min even in the absence of cytosolic Ca(2+) or ATP, suggesting that most of the
      calcium content of the vesicles is bound to a slowly exchanging Ca(2+) buffer.
      This large store buffers [Ca(2+)](SG) changes in the long-term but allows highly
      dynamic free [Ca(2+)](SG) changes to occur in seconds or minutes.

PMID- 15862347
TI  - Flash photolysis using a light emitting diode: an efficient, compact, and
      affordable solution.
AB  - Flash photolysis has become an essential technique for dynamic investigations of
      living cells and tissues. This approach offers several advantages for instantly
      changing the concentration of bioactive compounds outside and inside living cells
      with high spatial resolution. Light sources for photolysis need to deliver pulses
      of high intensity light in the near UV range (300-380 nm), to photoactivate a
      sufficient amount of molecules in a short time. UV lasers are often required as
      the light source, making flash photolysis a costly approach. Here we describe the
      use of a high power 365 nm light emitting diode (UV LED) coupled to an optical
      fiber to precisely deliver the light to the sample. The ability of the UV LED
      light source to photoactivate several caged compounds (CMNB-fluorescein, MNI
      glutamate, NP-EGTA, DMNPE-ATP) as well as to evoke the associated cellular Ca(2+)
      responses is demonstrated in both neurons and astrocytes. This report shows that
      UV LEDs are an efficient light source for flash photolysis and represent an
      alternative to UV lasers for many applications. A compact, powerful, and low-cost
      system is described in detail.

PMID- 15862348
TI  - Calcium buffering activity of mitochondria controls basal growth hormone
      secretion and modulates specific neuropeptide signaling.
AB  - Goldfish somatotropes contain multiple functionally distinct classes of non
      mitochondrial intracellular Ca(2+) stores. In this study, we investigated the
      role of mitochondrial Ca(2+) handling in the control of hormone secretion.
      Inhibition of mitochondrial Ca(2+) uptake with 10 microM ruthenium red (RR) and
      10 microM carbonyl cyanide m-chlorophenylhydrazone (CCCP) caused a small and
      reversible increase in cytosolic [Ca(2+)]. Despite relatively modest global
      Ca(2+) signals, RR and CCCP stimulated robust GH secretion under basal culture
      conditions. CCCP-stimulated hormone release was abolished in cells pre-incubated
      with 50 microM BAPTA-AM, suggesting that elevations in cytosolic [Ca(2+)] mediate
      this release of GH. Both caffeine-sensitive intracellular Ca(2+) stores and L
      type Ca(2+) channels can be the source of the Ca(2+) buffered by mitochondria in
      somatotropes. The stimulatory effect of RR on caffeine-stimulated GH release was
      enhanced dramatically in the presence of ryanodine, pointing to a complex
      interaction between these three Ca(2+) stores. Inhibition of mitochondrial Ca(2+)
      uptake with RR augmented GH release evoked by only one of the two endogenous
      gonadotropin-releasing hormones. Thus, we provide the first evidence that
      mitochondrial Ca(2+) buffering is differentially involved in specific agonist
      Ca(2+) signaling pathways and plays an important role in the control of basal GH
      release.

PMID- 15862349
TI  - Altered Ca2+ sparks and gating properties of ryanodine receptors in aging
      cardiomyocytes.
AB  - To investigate the cellular mechanisms for altered cardiac function in
      senescence, we measured Ca(2+) transients and Ca(2+) sparks in ventricular
      cardiomyocytes from 6- to 24-month-old Fisher 344 (F344) rat hearts. The single
      channel properties of ryanodine receptors from adult and senescent hearts were
      also studied. In senescent myocytes, we observed a decreased peak [Ca(2+)](i)
      amplitude and an increased time constant for decay (tau), both of which
      correlated with a reduced Ca(2+) content of the sarcoplasmic reticulum (SR). Our
      studies also revealed that senescent cardiomyocytes had an increased frequency of
      Ca(2+) sparks and a slight but statistically significant decrease in average
      amplitude, full-width-at-half-maximum (FWHM) and full-duration-at-half-maximum
      (FDHM). Single channel recordings of ryanodine receptors (RyR2) demonstrated that
      in aging hearts, the open probability (P(o)) of RyR2 was increased but the mean
      open time was shorter, providing a molecular correlate for the increased
      frequency of Ca(2+) sparks and decreased size of sparks, respectively. Thus,
      modifications of normal RyR2 gating properties may play a role in the altered
      Ca(2+) homeostasis observed in senescent myocytes.

PMID- 15862350
TI  - Polycystin-2 accelerates Ca2+ release from intracellular stores in Caenorhabditis
      elegans.
AB  - Polycystin-2, a member of the TRP family of calcium channels, is encoded by the
      human PKD2 gene. Mutations in that gene can lead to swelling of nephrons into the
      fluid-filled cysts of polycystic kidney disease. In addition to expression in
      tubular epithelial cells, human polycystin-2 is found in muscle and neuronal
      cells, but its cell biological function has been unclear. A homologue in
      Caenorhabditis elegans is necessary for male mating behavior. We compared the
      behavior, calcium signaling mechanisms, and electrophysiology of wild-type and
      pkd-2 knockout C. elegans. In addition to characterizing PKD-2-mediated
      aggregation and mating behaviors, we found that polycystin-2 is an intracellular
      Ca(2+) release channel that is required for the normal pattern of Ca(2+)
      responses involving IP(3) and ryanodine receptor-mediated Ca(2+) release from
      intracellular stores. Activity of polycystin-2 creates brief cytosolic Ca(2+)
      transients with increased amplitude and decreased duration. Polycystin-2, along
      with the IP(3) and ryanodine receptors, acts as a major calcium-release channel
      in the endoplasmic reticulum in cells where rapid calcium signaling is required,
      and polycystin-2 activity is essential in those excitable cells for rapid
      responses to stimuli.

PMID- 15862351
TI  - High-level expression and immunogenic properties of the recombinant rabbit
      hemorrhagic disease virus VP60 capsid protein obtained in Pichia pastoris.
AB  - The VP60 capsid protein from rabbit hemorrhagic disease virus (RHDV) (Spanish
      isolate AST/89) was cloned and expressed in Pichia pastoris. The transformed
      yeast was grown at high cell density and an expression level of about 1.5 g
      VP60L(-1) culture was obtained. The protein was detected associated with the cell
      debris fraction of the recombinant yeast after mechanical disruption. It was
      purified by a simple method and was obtained N-glycosylated with purity of
      approximately 70% as deduced from densitometry scan analysis. The recombinant
      product was antigenically similar to the native capsid protein as determined with
      polyclonal antibodies obtained from rabbits vaccinated with VP60 protein purified
      from native virus. The immunogenicity of VP60 protein purified from P. pastoris
      was demonstrated by ELISA in a vaccination experiment conducted with two groups
      of rabbits subcutaneously immunized. Animals vaccinated with VP60 in Freund's
      incomplete adjuvant developed a significant (p<0.01) virus-specific antibody
      response while the group injected with placebo remained seronegative. Preliminary
      results showed that the antigen administered within the cell debris fraction of
      the transformed yeast protected rabbits immunized by the oral route against an
      intramuscular challenge with 100 LD50 (16,000 hemagglutination units) of
      homologous virus.

PMID- 15862352
TI  - Screening enzyme-inhibitory activity in several ascidian species from Orkney
      Islands using protein tyrosine kinase (PTK) bioassay-guided fractionation.
AB  - Protein tyrosine kinases (PTK) play a crucial role in cell growth, cell
      differentiation and proliferation. In vertebrates, they are considered as
      potential oncogenes in development and growth. Some invertebrates utilize PTK
      inhibitors as a protection against microbial colonialization. With particular
      emphasis on PTK inhibitory potential for novel anticancer agents, activity
      against the epidermal growth factor receptor (EGFR) tyrosine kinase has been
      tested in ascidians for the first time. Twelve ascidian species collected around
      the Orkney Islands north of Scotland (UK) were tested for their activity against
      the epidermal growth factor receptor using a protein tyrosine kinase assay (PTK
      101 SIGMA). The crude extracts were partitioned according to their polarity (n
      hexane, ethyl acetate, n-butanol and water) and tested for inhibitory properties,
      followed by bioassay-guided fractionation of the partitions using different
      chromatographic methods and the PTK-101 assay. Structure elucidation of purified
      and PTK-active fractions was performed by nuclear magnetic resonance spectroscopy
      (NMR) and mass spectrometry (MS). Bioassay-guided fractionation led to the
      identification of several fractions enhancing or moderately reducing the enzyme
      activity. Strong inhibitory effects were detected in the ethyl acetate and the n
      butanol fractions of the baked bean ascidian, Dendrodoa grossularia. NMR analysis
      indicated the presence of the guanidinostyrene derivative tubastrine. This is the
      first documentation of this metabolite in ascidians. Structure analysis of
      tubastrine in comparison to other known PTK inhibitors may enhance our
      understanding of the structure and effect of the compounds and may help in the
      development of efficient therapeutic agents.

PMID- 15862353
TI  - Identification of extracellular lipases/esterases produced by Thermus
      thermophilus HB27: partial purification and preliminary biochemical
      characterisation.
AB  - Thermus thermophilus HB27 produces important levels of extracellular lipolytic
      activity when grown for 30 h at 70 degrees C in a complex medium. A method to
      detect esterase activity in these samples after non-reducing SDS-polyacrylamide
      electrophoresis was developed. The method, that implies the renaturalisation of
      the enzymes in the SDS-gels by washing with Triton X-100 at high temperatures,
      allowed detecting three esterases with different molecular weights (108, 62 and
      34 kDa, respectively). The electrophoretic mobility determined under different
      experimental conditions suggested that the 34- and 108 kDa-esterases might
      correspond with two oligomeric states of a sole enzyme (monomer and trimer).
      Dissociation of the trimer into the monomer started when the samples were heated
      at temperatures higher than 60 degrees C in the presence of sodium dodecyl
      sulphate. Evidences were found that indicated the independent nature of the 62
      kDa-esterase. A method to purify these enzymes from postincubates of T.
      thermophilus HB27 was developed following three steps: sodium cholate treatment,
      ethanol/ether precipitation and hydrophobic chromatography. In this way, an
      enzyme solution was obtained that contained the identified esterases/lipases. The
      partially purified enzymes showed an optimum of activity for the hydrolysis of p
      nitrophenyl laurate at alkaline pH values and 80 degrees C, a high thermal
      stability and were very stable in the presence of high concentrations of
      isopropanol.

PMID- 15862354
TI  - Expression and purification of a human, soluble Arylsulfatase A for Metachromatic
      Leukodystrophy enzyme replacement therapy.
AB  - The production of active Arylsulfatase A is a key step in the development of
      enzyme replacement therapy for Metachromatic Leukodystrophy. To obtain large
      amounts of purified Arylsulfatase A for therapeutic use, we combined a retroviral
      expression system with a versatile and rapid purification protocol that can
      easily and reliably be adapted to high-throughput applications. The purification
      method consists of an initial ion-exchange DEAE-cellulose chromatography step
      followed by immuno-affinity purification using a polyclonal antibody against a 29
      mer peptide of the Arylsulfatase A sequence. Immuno-adsorbed protein was eluted
      with a combination of acidic pH and an optimal concentration of the 29-mer
      peptide. This protocol reproducibly yielded approximately 100 microg of >99% pure
      human Arylsulfatase A, corresponding to 152 mU of enzyme activity, per liter of
      culture medium with properties similar to those of human non-recombinant protein.

PMID- 15862355
TI  - Substrate specificity for the 12beta-hydroxylation of bufadienolides by
      Alternaria alternata.
AB  - Hydroxylation is an important route to synthesize more hydrophilic compounds of
      pharmaceutical significance. Microbial hydroxylation offers advantages over
      chemical means for its high specificity. In this study, a fungal strain
      Alternaria alternata AS 3.4578 was found to be able to catalyze the specific
      12beta-hydroxylation of a variety of cytotoxic bufadienolides. Cinobufagin and
      resibufogenin could be completely metabolized by A. alternata to generate their
      12beta-hydroxylated products in high yields (>90%) within 8 h of incubation. A.
      alternata could also convert 3-epi-desacetylcinobufagin into 3-epi-12beta
      hydroxyl desacetylcinobufagin as the major product (70% yield). C-3
      dehydrogenated products were detected in these reactions in fair yields, while
      their accumulation was relatively slow. The 12beta-hydroxylation of
      bufadienolides could be significantly inhibited by the substitution of 1beta-, 5
      , or 16alpha-hydroxyl groups, and the 14beta,15beta-epoxy ring appeared to be a
      necessary structural requirement for the specificity. For the biotransformation
      of bufalin, a 14beta-OH bufadienolide, this reaction was not specific, and
      accompanied by 7beta-hydroxylation as a parallel and competing metabolic route.
      The biotransformation products were identified by comparison with authentic
      samples or tentatively characterized by high-performance liquid chromatography
      diode array detection-atmospheric pressure chemical ionization-mass spectrometry
      analyses.

PMID- 15862356
TI  - Expression and characterisation in E. coli of mutant forms of saporin.
AB  - In the present communication, we report on the expression and characterisation in
      Escherichia coli of mutant derivatives of saporin, a type 1 ribosome-inactivating
      protein from Saponaria officinalis L. The effects of substitution of Glu 176 with
      Lys and those of deletion of 19 amino acids at the C-terminal were evaluated both
      in vivo, testing the influence of expressed proteins on bacterial growth and in
      vitro measuring their N-glycosidase and supercoiled DNA relaxation activities.
      Results indicate that both modifications of the wild-type protein abolish its
      toxicity to bacterial cells and impair its enzymatic activity on polynucleotide
      substrates, either RNA or DNA.

PMID- 15862357
TI  - Chitin-binding domain based immobilization of D-hydantoinase.
AB  - Chitin-binding domain (ChBD) of chitinase A1 from Bacillus circulans WL-12
      comprises 45 amino acids and exhibits remarkably high specificity to chitin
      (Hashimoto, M., Ikegami, T., Seino, S., Ohuchi, N., Fukada, H., Sugiyama, J.,
      Shirakawa, M., Watanabe, T., 2000. Expression and characterization of the chitin
      binding domain of chintinase A1 from B. circulans WL-12. J. Bacteriol. 182, 3045
      3054.). To investigate the feasibility of exploiting ChBD as affinity tags to
      confine enzymes of interest on chitin, ChBD fused to the C-terminus of the gene
      encoding D-hydantoinase was constructed. Subsequent expression of the hybrid
      protein in Escherichia coli gave a soluble fraction accounting for 8% of total
      cell protein content. Direct adsorption of the ChBD-fused D-hydantoinase on
      chitin beads was carried out, and SDS-PAGE analysis showed that the linkage
      between the fusion protein and the affinity matrix was highly specific,
      substantially stable, and reversible. As compared to its free counterpart, the
      immobilized D-hydantoinase exhibited higher tolerance to heat and gained a half
      life of 270 h at 45 degrees C. In addition, the shelf life (defined as 50% of
      initial activity remained) of the immobilized enzyme stored at 4 degrees C was
      found to reach 65 days. Furthermore, D-hydantoinase immobilized on chitin could
      be reused for 15 times to achieve the conversion yield exceeding 90%. Overall, it
      illustrates the great usefulness of ChBD for enzyme immobilization.

PMID- 15862359
TI  - Immunoaffinity purification of SRT-tagged human creatine kinase by peptide
      elution.
AB  - The mouse monoclonal antibody (Mab), SRT10, recognizes a linear epitope of 10
      amino acids (ThrPheIleGlyAlaIleAlaThrAspThr). When these epitope-tagged fusion
      proteins are expressed in mammalian cells, the Mab can detect the tagged proteins
      by immunoblotting, immunocytochemistry and immunoprecipitation. Here, we describe
      an efficient method for the purification of SRT-tagged recombinant human creatine
      kinase (CK) transiently expressed in mammalian cells. This method utilizes the
      expression of the N-terminal- or C-terminal-tagged CK in transiently transfected
      HEK293 cells followed by binding to anti-SRT-agarose affinity resin and
      competitive elution with SRT peptide. Recombinant CK was purified near
      homogeneity as judged by SDS-PAGE.

PMID- 15862358
TI  - Effects of amino acid additions on ammonium stressed CHO cells.
AB  - Ammonium is a toxic and inhibitory byproduct of mammalian cell metabolism. At the
      end of a typical recombinant protein production campaign, the ammonium
      concentration can be as high as 10 mM, mainly due to glutamine metabolism.
      Intracellular pH (pH(i)) levels are sensitive to ammonium, which negatively
      impacts both cell growth and recombinant protein productivity. Ammonium also
      negatively affects the recombinant protein glycosylation profile, thus altering
      quality. Many strategies have been adopted to reduce ammonium accumulation, with
      limited results. This study investigated the addition of amino acids to the
      growth media for Chinese hamster ovary (CHO) cell cultures as a means of
      mitigating the negative effects of ammonium. Threonine, proline, and glycine
      additions improved CHO cell growth and recombinant protein levels. Further, the
      threonine, proline, and glycine additions positively impacted important metabolic
      parameters, including glucose consumption, lactate production, glutamine
      utilization, and final ammonium levels. Additionally, threonine, proline, and
      glycine increased the level of alpha(2,3)-linked sialic acid, galactose-beta(1,4)
      N-acetylglucosamine, and alpha(2,6)-linked sialic acid residues on the
      recombinant tissue plasminogen activator (t-PA). Thus, threonine, proline, and
      glycine can be used to mitigate some of the toxic effects of ammonium on cell
      growth, recombinant protein productivity, and protein quality.

PMID- 15862360
TI  - Use of immobilized cytochrome c as a ligand for affinity chromatography of
      thiosulfate dehydrogenase from Acidithiobacillus ferrooxidans.
AB  - Three matrices were used for immobilizing the cytochrome c: Sepharose CL-4B,
      Silasorb SPH amine and a laboratory-prepared new matrix based on crosslinked
      triazine (2,4,6-tris(aminoethylamine)-1,3,5-triazine) (TAT). Cytochrome c was
      immobilized on the matrices by several procedures and the amount of incorporated
      cytochrome c was determined. Cytochrome c immobilized on Sepharose CL-4B with
      periodate activation, cytochrome c immobilized on Silasorb-amine with
      carbodiimide activation and cytochrome c immobilized on crosslinked triazine were
      suitable for purification of thiosulfate dehydrogenase from Acidithiobacillus
      ferrooxidans. The yield with all matrices was about 90%. The purification factor
      of the above matrices was about 15. A new matrix based on TAT with cytochrome c
      represented a suitable way for thiosulfate dehydrogenase purification.

PMID- 15862361
TI  - Optimization of a Bifidobacterium longum production process.
AB  - Bifidobacteria are used as probiotics mainly in the dairy industry as cell
      suspensions or as freeze-dried additives. So far there have been no reports on a
      thorough investigation on factors influencing the production process or a
      statistical approach to the optimization thereof. A 2(8-4) fractional factorial
      design was used in determining the critical parameters influencing bioreactor
      cultivations of Bifidobacterium longum ATCC 15707. Glucose, yeast extract and l
      cysteine concentrations were found critical for the cultivation of this strain.
      Glucose and yeast extract concentrations were further studied together with
      temperature in a three factor central composite design. The optimized cultivation
      conditions were temperature 40 degrees C, yeast extract concentration 35 gl(-1)
      and glucose concentration 20 gl(-1). Freeze-drying of frozen cell suspensions of
      B. longum was studied first in controlled temperatures and thereafter with
      temperature programming experiments. The results were statistically evaluated. A
      temperature program with a 2 h temperature gradient from -10 to 0 degrees C, a 10
      h temperature gradient from 0 to +10 degrees C and a 12 h temperature hold at +10
      degrees C was found best for the freeze-drying process. Temperature programming
      reduced drying times by over 50% and improved the product activity by over 160%.

PMID- 15862363
TI  - Bioresorbable glass fibres facilitate peripheral nerve regeneration.
AB  - This is a proof of principle report showing that fibres of Bioglass 45S5 can form
      a biocompatible scaffold to guide regrowing peripheral axons in vivo. We
      demonstrate that cultured rat Schwann cells and fibroblasts grow on Bioglass
      fibres in vitro using SEM and immunohistochemistry, and provide qualitative and
      quantitative evidence of axonal regeneration through a Silastic conduit filled
      with Bioglass fibres in vivo (across a 0.5 cm interstump gap in the sciatic
      nerves of adult rats). Axonal regrowth at 4 weeks is indistinguishable from that
      which occurs across an autograft. Bioglass fibres are not only biocompatible and
      bioresorbable, which are absolute requirements of successful devices, but are
      also amenable to bioengineering, and therefore have the potential for use in the
      most challenging clinical cases, where there are long inter-stump gaps to be
      bridged.

PMID- 15862362
TI  - Diffusive and convective transport through hollow fiber membranes for liver cell
      culture.
AB  - For an efficient membrane bioreactor design, transport phenomena determining the
      overall mass flux of metabolites, catabolites, cell regulatory factors, and
      immune-related soluble factors, need to be clarified both experimentally and
      theoretically. In this work, experiments and calculations aimed at discerning the
      simultaneous influence of both diffusive and convective mechanisms to the
      transport of metabolites. In particular, the transmembrane mass flux of glucose,
      bovine serum albumin (BSA), APO-transferrin, immunoglobulin G, and ammonia was
      experimentally measured, under pressure and concentration gradients, through high
      flux microporous hydrophilic poly-ether-sulphone (PES-HFMs) and poly-sulphone
      hollow fiber membranes (PS-HFMs). These data were analyzed by means of a model
      based on the mechanism of capillary pore diffusion, assuming that solute
      spherical molecules pass through an array of solvent-filled cylindrical pores
      with a diffusive permeation corrected for friction and steric hindrances.
      Additionally, resistances to the mass transfer were taken into account.
      Convective permeation data were discussed in terms of morphological properties of
      the polymeric membranes, molecular Stokes radius, and solute-membrane
      interactions according to information given by contact angle measurements. The
      observed steady-state hydraulic permeance of PS-HFMs was 0.972 L/m2hmbar, about
      15.6-fold lower than that measured for PES-HFMs (15.2 L/m2h); in general, PS-HFMs
      provided a significant hindrance to the transport of target species. Diffusion
      coefficients of metabolites were found to be similar to the corresponding values
      in water through PES-HFMs, but significantly reduced through PS-HFMs
      (D(Glucose)(Membrane)=2.8x10(-6)+/-0.6x10(-6)cm2/s, D(BSA)(Membrane)=6.4 x 10(
      7)+/-1 x 10(-7)cm(/s, D(Apotransferrin)(Membrane)=2.3 x 10(-7)+/-0.25 x 10(
      7)cm2/s).

PMID- 15862364
TI  - Management of the failed biaxial wrist replacement.
AB  - Nine cases of failed biaxial wrist replacement underwent revision surgery and
      subsequent clinical and radiographic assessment at a mean follow-up of 28 months.
      Clinical assessment included the hospital for special surgery (HSS) and
      activities of daily living scoring systems. Five patients had a revision biaxial
      wrist replacement, three had wrist fusions and two underwent an excision
      arthroplasty. The mean HSS score was 73 for the revision biaxial replacements, 63
      for the wrist fusions and 92 for the excision arthroplasties. The mean activities
      for daily living score was 16 for the revision biaxial replacements, 14 for the
      wrist fusion and 20 for the excision arthroplasties. Despite the experience of
      implant failure, six patients would still choose a primary wrist replacement
      again. All patients in this small series appear to have had good clinical
      outcomes. Revision to another wrist replacement appears no worse than a wrist
      fusion in the short term and patients value the preservation of movement that an
      implant offers.

PMID- 15862365
TI  - Assessment of sensibility after nerve injury and repair: a systematic review of
      evidence for validity, reliability and responsiveness of tests.
AB  - Recovery of sensibility after peripheral nerve injury and repair needs to be
      assessed using psychometrically robust measures. In this study the literature was
      reviewed to identify what tests are available to quantify sensibility and to
      assess their validity, reliability and responsiveness. The databases Medline,
      CINAHL, Embase and AMED were searched for studies reporting the psychometric
      properties of sensibility tests. While there is a plethora of tests and studies
      reporting the outcomes after peripheral nerve suture only a few of the tests have
      evidence of validity, reliability and responsiveness. Currently the touch
      threshold test using monofilaments such as the Weinstein Enhanced Sensory Test
      (WEST) or Semmes-Weinstein Monofilament Test (SWMT) and the shape-texture
      identification (STI) test for tactile gnosis are the only tests which meet
      criteria for a standardized test and have had their psychometric properties
      evaluated and quantified.

PMID- 15862367
TI  - Fingertip skin wrinkling - the effect of varying tonicity.
AB  - Fingertip skin wrinkling after prolonged immersion in water is a well-recognized
      phenomenon, whereas a denervated digit does not exhibit normal skin wrinkling
      while a finger with a regenerated or repaired nerve shows at least partial
      reappearance of wrinkling. This is the basis for the bedside immersion-wrinkling
      test of autonomic digital nerve function. The exact mechanism of fingertip skin
      wrinkling is still subject to controversy. The purpose of this study was to
      investigate the relationship between the tonicity of a solution and the time
      elapsed to skin wrinkling. Fourteen healthy volunteers (28 hands) were recruited
      for investigation. We submerged all 28 hands in solutions of varying tonicity
      while maintaining all other parameters constant. We found that increased tonicity
      significantly slowed the time to wrinkling (TTW). Hypotonic solutions such as
      water should be used when performing clinical bedside testing for autonomic
      digital nerve function.

PMID- 15862366
TI  - Extensor carpi ulnaris problems at the wrist--classification, surgical treatment
      and results.
AB  - Twenty-eight extensor carpi ulnaris lesions at the wrist were treated surgically
      between 1990 and 2002. Fifteen patients had an isolated extensor carpi ulnaris
      tenosynovitis or tendinopathy, five had extensor carpi ulnaris dislocation, four
      had an extensor carpi ulnaris subluxation and four had an extensor carpi ulnaris
      rupture. Seventeen patients first developed their symptoms while playing sports.
      At a mean follow-up of 23 months, twenty-two patients had returned to their
      previous activities. Seven of the 27 patients had lost more than 30% of their
      grip strength and five had restricted wrist motion. Two needed an extensor carpi
      ulnaris tenolysis. Pure isolated extensor carpi ulnaris lesions are rare and
      associated ulnar sided lesions (eleven triangular fibrocartilage complex tears
      and four lunotriquetral ligament tears), as well as possible predisposing factors
      (seven anomalous tendon slips, four ulnar styloid non-unions and one flat
      extensor carpi ulnaris tendon groove), were frequent. A classification of
      extensor carpi ulnaris tendon and subsheath lesions was developed to allow the
      surgeon to adequately evaluate the different components of these lesions.

PMID- 15862368
TI  - Long-term follow-up of surgical treatment for thumb duplication.
AB  - There are few long-term follow-up reports concerning the treatment of thumb
      duplication. We reviewed the treatment of 19 of 74 patients treated at our
      institution between 1956 and 2002. The average follow-up was 22 (range, 7 years
      to 35 years) years. Satisfactory function was achieved in 18 thumbs and cosmesis
      in 12 thumbs. Six thumbs were cold-intolerant at this late follow-up. Pinch
      strength was similar to the contralateral normal thumbs. Collateral ligament
      repair did not significantly contribute to joint stability. An objective method
      of postoperative evaluation showed good results in five, fair results in 12 and
      poor results in two thumbs.

PMID- 15862369
TI  - Sagittal wrist motion of carpal bones following intraarticular fractures of the
      distal radius.
AB  - Forty patients (mean age, 37 years) with intraarticular C2 and C3 Colles
      fractures were treated by open reduction, internal fixation and bone grafting. At
      a mean follow-up of 8 years radiocarpal and midcarpal motion was evaluated, the
      depth of the articular surface of the distal radius in the sagittal plane was
      measured and the presence of arthritis was noted. The fractures healed with a
      mean palmar tilt of 6 degrees , a mean ulnar tilt of 18 degrees and ulna variance
      within 1 mm of the contralateral side. The depth of the articular surface of the
      distal radius was 1.3 mm greater than the uninvolved side. Measurement of carpal
      bone angles relative to the radius in maximum flexion and extension revealed
      lunate extension of 23 degrees , lunate flexion of 15 degrees , capitate
      extension of 62 degrees , capitate flexion of 40 degrees . There was a
      significant correlation between articular surface depth and radiocarpal motion.

PMID- 15862370
TI  - Supplementary core sutures increase resistance to gapping for flexor digitorum
      profundus tendon to bone surface repair - an in vitro biomechanical analysis.
AB  - We evaluated the effects of two types of supplementary core sutures on the
      tensile properties and resistance to gap formation of flexor digitorum profundus
      (FDP) tendon-bone repairs. Forty-five human cadaver FDP tendons were sharply
      released from their insertion sites and repaired to bone utilizing one of three
      repair techniques: four-strand modified Becker core suture (Becker only),
      modified Becker plus a figure-of-eight supplementary core suture (Becker plus
      figure-of-eight), and modified Becker plus a supplementary core suture using a
      bone anchor (Becker plus anchor). Ultimate (maximum) force did not differ between
      repair groups. However, addition of a supplementary suture significantly
      increased repair-site stiffness and the 1, 2 and 3 mm gap forces, while
      decreasing the gap at 20 N compared to the Becker only suture (P<0.05). The only
      difference between the two supplementary suture groups was that the Becker plus
      anchor group had increased stiffness compared to the Becker plus figure-of-eight
      group. In conclusion, a supplementary figure-of-eight suture and a supplementary
      suture using a bone anchor provide enhanced resistance to gap formation for FDP
      tendon-bone repairs.

PMID- 15862371
TI  - An assessment of the tensile properties and technical difficulties of two- and
      four-strand flexor tendon repairs.
AB  - This study compares the mechanical properties of locking Kessler and four-strand
      flexor tendon repairs and examines for difficulties related to technical ability.
      Two trainee surgeons each carried out 10 locking Kessler and 10 four-strand
      single-cross flexor tendon repairs on an in vitro porcine model. Outcome measures
      included gap formation and ultimate forces, operative time and repair bulk.
      Ultimate force was 81% greater for the four-strand repair compared to the Kessler
      (52 N, SD 5, versus 29 N, SD 6). Operating times were similar between the two
      techniques (Kessler 10.0 minutes, four strand 10.1 minutes). Rupture force and
      operating times improved slightly during the study for the Kessler repairs, but
      in the four strand repairs results remained stable throughout the study. We
      conclude that the single-cross four-strand repair tolerates superior loads yet is
      no more technically demanding than the modified Kessler, and can be reliably
      performed without additional operating time.

PMID- 15862372
TI  - Chronic sclerosing osteomyelitis of a metacarpal.
AB  - Chronic sclerosing osteomyelitis in a metacarpal is presented. Bacterial cultures
      were negative, and radiographs and an isotope scan were non-specific.
      Histopathological assessment confirmed the diagnosis. Iliac bone grafting
      resulted in symptomatic relief to the patient.

PMID- 15862373
TI  - The prevalence of wrist ganglia in an asymptomatic population: magnetic resonance
      evaluation.
AB  - Magnetic resonance imaging (MRI) was performed on the wrists of 103 asymptomatic
      volunteers. The images were evaluated independently by two musculoskeletal
      radiologists and one orthopaedic surgeon. Wrist ganglia were identified in 53 out
      of the 103 wrists. The average long and short axes measurements were 8 mm (range
      3-22) and 3 mm (range 2-10), respectively. Seventy per cent of the ganglia
      originated from the palmar capsule in the region of the interval between the
      radioscaphocapitate ligament and the long radiolunate ligament. Fourteen per cent
      of the ganglia were dorsal and originated from the dorsal, distal fibres of the
      scapholunate ligament. Two ganglia had surrounding soft tissue oedema and one had
      an associated intraosseous component. Unlike previous surgical and pathological
      series, our study showed that palmar wrist ganglia are more common than dorsal
      wrist ganglia. The vast majority of these asymptomatic ganglia occur without
      associated ligamentous disruption, soft tissue oedema or intraosseous
      communication.

PMID- 15862374
TI  - The porcine forelimb as a model for human flexor tendon surgery.
AB  - Technical skills have been shown to transfer very well from bench models to
      practical use. The central two rays of 30 forelimbs of pigs were dissected and
      anatomical observations were made. The rays contained deep and superficial flexor
      tendons enclosed in a fibro-osseous tunnel and these were present in all 60
      specimens. The fibrous part of the tunnel had specific constant condensations in
      annular and oblique directions which were present in all 60 rays. The anatomy of
      the porcine forelimb digital flexor tendon system is sufficiently similar to the
      human system to be used as a model for surgeons wishing to master the technical
      aspects of zone II flexor tendon repair. This paper proposes the porcine forelimb
      as a bench model for zone II flexor tendon repair.

PMID- 15862375
TI  - Historical prostheses. 1925.

PMID- 15862376
TI  - Symptomatic ulnar neural loop at the wrist.
AB  - A case report is presented of a patient found at surgery to have an anomalous
      neural loop of the ulnar nerve at the wrist. The literature is reviewed. Although
      previous cases have been reported with compressive symptoms or as a coincidental
      finding we believe that this is the first case reported where symptoms were
      directly related to the presence of the loop without evidence of a compressive
      lesion.

PMID- 15862377
TI  - Re: Silastic replacement of metacarpal after resection of giant cell tumor.

PMID- 15862378
TI  - Recent remembrance by Mr. Bonney of Donal Brooks.

PMID- 15862379
TI  - "The two point discrimination test--time for a reappraisal?".

PMID- 15862381
TI  - Re: "The Sauve-Kapandji procedure and the Darrach procedure for distal radioulnar
      joint dysfunction after colles' fracture".

PMID- 15862383
TI  - A comparison of fusion, trapeziectomy, and silastic replacement for the treatment
      of osteoarthritis of the trapeziometacarpal joint.

PMID- 15862385
TI  - Re: Carpal Tunnel syndrome and work.

PMID- 15862387
TI  - Staged reconstruction for malunited fractures of the distal radius.

PMID- 15862390
TI  - Re: IFSSH Flexor Tendon Committee Report.

PMID- 15862391
TI  - Response patterns in adult forest trees to chronic ozone stress: identification
      of variations and consistencies.
AB  - The responsiveness of adult beech and spruce trees to chronic O(3) stress was
      studied at a free-air O(3) exposure experiment in Freising/Germany. Over three
      growing seasons, gas exchange characteristics, biochemical parameters,
      macroscopic O(3) injury and the phenology of leaf organs were investigated, along
      with assessments of branch and stem growth as indications of tree performance. To
      assess response pattern to chronic O(3) stress in adult forest trees, we
      introduce a new evaluation approach, which provides a comprehensive, readily
      accomplishable overview across several tree-internal scaling levels, different
      canopy regions and growing seasons. This new approach, based on a three-grade
      colour coding, combines statistical analysis and the proficient ability of the
      "human eye" in pattern recognition.

PMID- 15862392
TI  - Responses of sensitive and tolerant bush beans (Phaseolus vulgaris L.) to ozone
      in open-top chambers are influenced by phenotypic differences, morphological
      characteristics, and the chamber environment.
AB  - Responses of bush bean (Phaseolus vulgaris L.) lines 'S156' (O(3)-sensitive) and
      'R123' (O(3)-tolerant), and cultivars 'BBL 290' (O(3)-sensitive) and 'BBL 274'
      (O(3)-tolerant) to ambient ozone (O(3)) were investigated during the 2001 and
      2002 growing seasons. Seedlings were grown in pots inside open-top chambers
      (OTCs), with charcoal filtered (CF) and non-filtered (NF) ambient air, and in non
      chambered ambient air (AA) plots. Growth parameters from individual plants were
      evaluated after harvests at the end of vegetative (V(4)) and reproductive (R(10))
      growth phases. Results at V(4) indicated that CF did not provide additional
      benefits over NF in 'S156' in 2001 and 2002. In contrast, exposure to CF
      significantly impaired the growth of 'R123'. At the end of R(10), 'S156' produced
      more pods, most of which remained immature, and contained fewer seeds or were
      more frequently aborted, whereas pods produced in 'R123' reached pod maturation
      and senescence more consistently. Despite increased seed weights inside the OTCs,
      as observed in 'S156', differences between the two lines were insignificant when
      grown outside OTCs. Results from the 'BBL 290'/'BBL 274' pair, especially at V(4)
      phase, remained inconclusive. Plant morphological characteristics, variabilities
      in environmental conditions, and 'chamber effects' inside OTCs were influential
      in determining plant response to ambient O(3).

PMID- 15862393
TI  - Factors affecting the effects of EDU on growth and yield of field-grown bush
      beans (Phaseolus vulgaris L.), with varying degrees of sensitivity to ozone.
AB  - The effects of foliar applications of ethylenediurea (EDU) on responses to ozone
      by field-grown bush bean (Phaseolus vulgaris L.) lines 'S156' (O(3)-sensitive)
      and 'R123' (O(3)-tolerant), and cultivars 'BBL 290' (O(3)-sensitive) and 'BBL
      274' (O(3)-tolerant) were investigated during the 2001 and 2002 growing seasons.
      EDU was applied weekly to designated plants between primary leaf expansion and
      pod senescence. Results were compared with control plants at harvests made at pod
      maturation and pod senescence. In 2001, average hourly ambient O(3)
      concentrations ranged between 41 and 59 ppb for a total of 303 h; in 2002, for
      355 h. EDU applications prior to pod maturation significantly increased the
      number of marketable pods in 'R123', but not for the other cultivars. Harvests at
      pod senescence showed significant improvements in crop yield production in EDU
      treated 'S156' plants, whereas for EDU-treated 'R123' plants significant
      reductions were determined in above-ground biomass and seed production. In
      contrast, results from 'BBL 290' and 'BBL 274' at both harvest points were
      inconclusive. Growth and reproductive responses of O(3)-sensitive and O(3)
      tolerant bush bean plants to EDU applications varied, depending on developmental
      stages, duration of EDU applications, and fluctuations in ambient O(3).

PMID- 15862394
TI  - Accumulating pollutants in conifer needles on an Atlantic island - a case study
      with Pinus canariensis on Tenerife, Canary Islands.
AB  - Concentrations of potential pollutant elements Na, Cl, and S were investigated in
      needles of Pinus canariensis grown at 55 field plots in Tenerife. Microelement
      concentrations (including heavy metals) were measured at a subset of 18 plots. Na
      and Cl concentrations were high at low elevations (up to 8 mg g(-1) Cl and 5.5 mg
      g(-1) Na). Na/Cl ratio close to standard seawater indicated sea spray influence
      up to 1200 m a.s.l. Only at few plots, sulphur concentrations indicated possible
      pollutant impact. Cluster and correlation analyses identified a related group of
      V, As, Cr, Fe, Mo, Ni, Cu, Pb, and Al, possibly related to traffic exhaust
      aggregated with soil particles. Mainly north-eastern, lower elevated plots were
      exposed to those immissions, but metal concentrations were generally low compared
      to data from other studies. In conclusion, seawater and soil particles explained
      most of the element distribution pattern in pine needles in Tenerife, but strong
      indications for some effect of local sources of air pollutants were detected.

PMID- 15862395
TI  - Bioavailability of contaminants estimated from uptake rates into soil
      invertebrates.
AB  - It is often argued that the concentration of a pollutant inside an organism is a
      good indicator of its bioavailability, however, we show that the rate of uptake,
      not the concentration itself, is the superior predictor. In a study on zinc
      accumulation and toxicity to isopods (Porcellio scaber) the dietary EC(50) for
      the effect on body growth was rather constant and reproducible, while the
      internal EC(50) varied depending on the accumulation history of the animals. From
      the data a critical value for zinc accumulation in P. scaber was estimated as 53
      microg/g/wk. We review toxicokinetic models applicable to time-series
      measurements of concentrations in invertebrates. The initial slope of the uptake
      curve is proposed as an indicator of bioavailability. To apply the dynamic
      concept of bioavailability in risk assessment, a set of representative organisms
      should be chosen and standardized protocols developed for exposure assays by
      which suspect soils can be evaluated.

PMID- 15862396
TI  - Selected chlorobornanes, polychlorinated naphthalenes and brominated flame
      retardants in Bjornoya (Bear Island) freshwater biota.
AB  - Levels of selected sparsely investigated persistent organic pollutants (POPs)
      have been measured in organisms from two Arctic lakes on Bjornoya (Bear Island).
      Elevated levels of chlorobornanes (CHBs) (up to 46.7 ng/g wet weight=ww),
      polybrominated diphenyl ethers (PBDEs) (up to 27.2 ng/g ww), polybrominated
      biphenyls (PBBs) (up to 1.1 ng/g ww) and polychlorinated naphthalenes (PCNs, only
      4 congeners) (up to 62.7 pg/g ww), were measured in biota from Lake Ellasjoen. In
      Lake Oyangen, located only 5 km north of Ellasjoen, levels of these contaminants
      were significantly lower. delta(15)N-values were 7-10 per thousand higher in
      organisms from Ellasjoen as compared to Oyangen. This is attributed to biological
      inputs related to seabird activities. The present study illustrates that
      contaminants such as CHBs, brominated flame retardants and PCNs accumulate in the
      Ellasjoen food web in a manner similar to PCBs and conventional organochlorine
      pesticides. Transport mechanisms that control PCB and DDT distributions, i.e.
      atmospheric long-range transport and biotransport by seabirds, are also relevant
      for the contaminants investigated in the present study.

PMID- 15862397
TI  - Atmospheric trace metal pollution in the Naples urban area based on results from
      moss and lichen bags.
AB  - The results of trace element content analysed in Sphagnum capillifolium and
      Pseudevernia furfuracea exposed in bags in 1999 are reconsidered to evaluate the
      reliability of moss and lichen transplants to detect urban trace element
      atmospheric pollution, using Naples as a case example. After 4 months' exposure,
      trace element concentrations were at least twice as high as the pre-exposure
      values and in general higher in Sphagnum than in Pseudevernia. Moss samples were
      enriched in the following order: As=Cu>Mo>Pb>V>Co>Cr>Zn; lichen samples in the
      order: Mo>Cu>As=Co=Ni>V>Pb. Based on the calculation of a cumulative load factor,
      all sites located along the coast had higher trace element loads compared to
      sites in the hilly inland area. Complementary SEM, TEM and EDS observations
      showed, despite significant damage to tissue and cell integrity, the recurrent
      presence of particulate matter in moss and lichen, indicating the considerable
      presence of dust in the urban atmosphere which, according to chemical
      composition, may be due both to anthropogenic and natural sources such as
      volcanic rock and soil and sea salts.

PMID- 15862398
TI  - Earthworm responses to Cd and Cu under fluctuating environmental conditions: a
      comparison with results from laboratory exposures.
AB  - Laboratory toxicity tests are usually conducted under stable ambient conditions,
      while exposures in ecosystems occur in a fluctuating climate. To assess how
      climate influences the toxicity of Cu and Cd for the earthworm Lumbricus
      rubellus, this study compared effects for life-cycle parameters (survival,
      reproduction), cellular status (lysosomal membrane stability), gene expression
      (transcript of the metal binding protein metallothionein-2) and tissue metal
      concentration measured under outdoor conditions, with the same responses under
      constant conditions as measured by Spurgeon et al. [Spurgeon, D.J., Svendsen, C.,
      Weeks, J.M., Hankard, P.K., Stubberud, H.E., Kammenga, J.E., 2003. Quantifying
      copper and cadmium impacts on intrinsic rate of population increase in the
      terrestrial oligochaete Lumbricus rubellus. Environmental Toxicology and
      Chemistry 22, 1465-1472]. Both metals were found to significantly influence
      earthworm reproduction, compromise lysosomal membrane stability and induce MT-2
      gene expression in the outdoor system. Comparison with physiological and life
      cycle responses in the laboratory indicated similar response patterns and effect
      concentrations for Cu. For Cd, lysosomal membrane stability and MT-2 expression
      showed comparable responses in both exposures. Juvenile production rate, however,
      gave different dose response relationships, with the EC-(50) in the outdoor test
      approximately half that in the laboratory test. A difference in Cd accumulation
      was also seen. Overall, however, the comparison indicated only a marginal effect
      of environmental fluctuations typical for northern temperate Europe on earthworm
      sensitivity to the two metals.

PMID- 15862399
TI  - Uptake, absorption efficiency and elimination of DDT in marine phytoplankton,
      copepods and fish.
AB  - Uptake, absorption efficiency and elimination of DDT were measured in marine
      phytoplankton, copepods (Acartia erythraea) and fish (mangrove snappers Lutjanus
      argentimaculatus). The uptake rate constant of DDT from water decreased with
      increasing trophic level. The dietary absorption efficiency (AE) of DDT was 10
      29% in copepods and 72-99% in fish. Food concentration did not significantly
      affect the AEs of DDT, but the AEs varied considerably among the different food
      diets. The elimination rate constants of DDT by the copepods were comparable
      following uptake from the diet and from the water. Elimination of DDT from the
      fish was exceedingly low. Both aqueous and dietary uptake are equally important
      for DDT accumulation in the copepods. In fish, dissolved exposure is a more
      significant route than intake from the diet. The predicted trophic transfer
      factors in the copepods and the fish are consistent with the field measurements
      in marine zooplankton and fish.

PMID- 15862400
TI  - Contamination status and accumulation features of persistent organochlorines in
      pet dogs and cats from Japan.
AB  - Concentrations of persistent organochlorines (OCs) such as polychlorinated
      dibenzo-p-dioxin (PCDDs), dibenzofurans (PCDFs), biphenyls,
      dichlorodiphenyltrichloroethane and their metabolites (DDTs),
      hexachlorocyclohexane isomers, hexachlorobenzene, and chlordane compounds were
      determined in genital organs of pet dogs and cats and pet foods from Japan.
      Levels of OCs in dogs were relatively lower than those in cats, while residue
      levels in their diets were almost similar, implying that accumulation and
      elimination mechanisms of these contaminants are different between dogs and cats.
      When bioconcentration factors (BCFs) were estimated from concentrations of OCs in
      dogs, cats, and their diets, BCFs of all the OCs except PCDD/DFs exceeded 1.0 in
      cats. On the other hand, in all the dogs, BCFs of DDTs were below 1.0, suggesting
      that dogs do not bioconcentrate DDTs. Furthermore, BCFs of all the OCs except
      PCDD/DFs in dogs were notably lower than those in cats, suggesting that dogs have
      higher metabolic and elimination capacity for these contaminants than cats. When
      residue levels of OCs in livers, adipose tissue, and genital organs of two pet
      dogs were examined, hepatic sequestration of PCDD/DFs and oxychlordane was
      observed.

PMID- 15862401
TI  - Benzo[a]pyrene co-metabolism in the presence of plant root extracts and exudates:
      Implications for phytoremediation.
AB  - Benzo[a]pyrene, a high molecular weight (HMW) polycyclic aromatic hydrocarbon
      (PAH) was removed from solution by Sphingomonas yanoikuyae JAR02 while growing on
      root products as a primary carbon and energy source. Plant root extracts of osage
      orange (Maclura pomifera), hybrid willow (Salix albaxmatsudana), or kou (Cordia
      subcordata), or plant root exudates of white mulberry (Morus alba) supported 15
      20% benzo[a]pyrene removal over 24 h that was similar to a succinate grown
      culture and an unfed acetonitrile control. No differences were observed between
      the different root products tested. Mineralization of (14)C-7-benzo[a]pyrene by
      S. yanoikuyae JAR02 yielded 0.2 to 0.3% (14)CO(2) when grown with plant root
      products. Collectively, these observations were consistent with field
      observations of enhanced phytoremediation of HMW PAH and corroborated the
      hypothesis that co-metabolism may be a plant/microbe interaction important to
      rhizoremediation. However, degradation and mineralization was much less for root
      product-exposed cultures than salicylate-induced cultures, and suggested the
      rhizosphere may not be an optimal environment for HMW PAH degradation by
      Sphingomonas yanoikuyae JAR02.

PMID- 15862402
TI  - Metal-contaminated soil remediation by means of paper mill sludges addition:
      chemical and ecotoxicological evaluation.
AB  - Metal pollution of soils is a great environmental problem. The major risks due to
      metal pollution of soil consist of leaching to groundwater and potential toxicity
      to plants and/or animals. The objective of this study is to evaluate by means of
      chemical and ecotoxicological approach the effects of paper mill sludge addition
      on the mobile metal fraction of polluted metal soils. The study was carried out
      on acidic soil derived from mining activities and thus polluted with heavy
      metals, and on two paper mill sludges having different chemical features. The
      results obtained by leaching experiments showed that the addition of a paper mill
      sludge, consisting mainly of carbonates, silicates and organic matter, to a heavy
      metal polluted soil produces a decrease of available metal forms. The carbonate
      content seems to play a key role in the chemical stabilisation of metals and
      consequently in a decrease of toxicity of soil. The leached solutions have a non
      toxic effect. The mild remediation by addition of sludge has moreover a lasting
      effect.

PMID- 15862403
TI  - Occurrence of polybrominated diphenylethers, polychlorinated dibenzo-p-dioxins,
      dibenzofurans and biphenyls in coastal sediments from Spain.
AB  - Fifteen sediment samples were analysed in order to determine their content of
      polybrominated diphenylethers (PBDEs), polychlorinated dibenzo-p-dioxins (PCDDs),
      dibenzofurans (PCDFs) and biphenyls (PCBs). Samples were collected from several
      hot spots on the Spanish coast, such as the harbours of Almeria and Tarragona,
      and the mouths of the Besos and Llobregat rivers in Barcelona. A generic
      analytical procedure based on Soxhlet extraction followed by an automated cleanup
      system and gas chromatography-ion trap-mass spectrometry was employed for
      determining the toxic congeners of PCDDs and PCDFs, as well as dioxin-like PCBs.
      As regards PBDE determinations, a rapid method based on the use of selective
      pressurized liquid extraction followed by gas chromatography-negative ion
      chemical ionization-mass spectrometry was applied. Total toxicity equivalent (WHO
      TEQ) values were calculated using the toxicity equivalent factors proposed by WHO
      for dioxin-like PCBs, PCDDs and PCDFs. WHO-TEQ values ranged from 0.3 to 75 pg/g
      dry weight (dw), with PCB contribution on the toxicity of the samples between 1
      and 84%. Total PBDE levels ranged from 2.7 to 134 ng/g dw, with BDE-209
      contribution on the total PBDE contamination between 50 and 99%.

PMID- 15862404
TI  - Review of passive accumulation devices for monitoring organic micropollutants in
      the aquatic environment.
AB  - Over the past 15 years passive sampling devices have been developed that
      accumulate organic micropollutants and allow detection at ambient sub ng/l
      concentrations. Most passive accumulation devices (PADs) are designed for 1-4
      weeks field deployment, where uptake is governed by linear first order kinetics
      providing a time weighted average of the exposure concentration. Semipermeable
      membrane devices (SPMDs) are the most comprehensively studied PADs, but other
      samplers may also be considered for aquatic monitoring purposes. The
      applicability of the PADs is reviewed with respect to commonly monitored aqueous
      matrices and compounds, the detection limits, and for use in quantitative
      monitoring related to requirements embedded in the EU Water Framework Directive,
      the US and EU Water Quality Criteria, and the Danish monitoring aquatic
      programme. The PADs may monitor >75% of the organic micropollutants of the
      programmes. Research is warranted regarding the uptake in PADs in low flow
      environments and for the development of samplers for polar organic compounds.

PMID- 15862405
TI  - Survey of organotin compounds in rivers and coastal environments in Portugal 1999
      2000.
AB  - In the period from April 1999 to May 2000, organotin pollution, namely butyl and
      phenyltins, was investigated in coastal and continental waters (46 stations),
      estuarine sediments (15 stations) and mussels (Mytilus galloprovincialis) (13
      stations) throughout Portugal. Sampling points were chosen in areas of specific
      industrial, agricultural and harbor activities. Butyltins (BTs) were the only tin
      species identified of which tributyltin (TBT) was found in the whole area.
      Concentrations of TBT in river water ranged from 3 to 30 ng L(-1) (as Sn), marine
      sediment ranged from 4 to 12 microg kg(-1) (as Sn), whereas concentrations in
      mussel tissue ranged from 2.5 to 490 microg kg(-1) (as Sn). Given that some water
      samples appeared to be contaminated by higher monobutyltin (MBT) and dibutyltin
      (DBT) concentrations, the role of biological degradation and direct inputs from
      agricultural and industrial applications areas are discussed. The study compares
      depleted butyltin pollution in sediments and mussels of the Portuguese coastline
      associated with antifouling paints with previously reported levels. Inputs in
      river waters are more related to (i) PVC leaching and (ii) industrial sources, in
      some cases discharged by municipal wastewaters.

PMID- 15862406
TI  - Diets and cardiovascular disease: an evidence-based assessment.
AB  - With rising obesity, despite low-fat diet recommendations, there is an increased
      interest in weight loss and alternative dietary approaches for cardiovascular
      health. Physicians must have an understanding of the literature to better counsel
      their patients about diets and cardiovascular disease. This review examines
      several dietary approaches to cardiovascular health and evaluates the available
      scientific evidence regarding these diets.

PMID- 15862407
TI  - Health insurance and cardiac transplantation: a call for reform.
AB  - Cardiac transplantation is an accepted therapy for patients with end-stage heart
      failure (ESHF). Presently in the U.S., patients with ESHF need to have health
      insurance or another funding source to be considered eligible for cardiac
      transplantation. Whether it is appropriate to exclude potential recipients solely
      due to lack of finances has received considerable interest including being the
      subject of a recent major motion picture (John Q, New Line Cinema, 2002).
      However, one important aspect of this debate has been underappreciated and
      insufficiently addressed. Specifically, organ donation does not require the donor
      to have health insurance. Thus, individuals donate their hearts although they
      themselves would not have been eligible to receive a transplant had they needed
      one. By querying Siminoff's National Study of Family Consent to Organ Donation
      database, we find that this situation is not uncommon as approximately 23% of
      organ donors are uninsured. Herein we also discuss how the funding requirement
      for cardiac transplantation has been addressed by the federal government in the
      past, its implications on the organ donor consent process, and its potential
      impact on organ donation rates. We call for a government-sponsored,
      multidisciplinary task force to address this situation in hopes of remedying the
      inequities in the present system of organ allocation.

PMID- 15862408
TI  - The relation of dosing to clopidogrel responsiveness and the incidence of high
      post-treatment platelet aggregation in patients undergoing coronary stenting.
AB  - OBJECTIVES: We determined the effect of clopidogrel dosing on the incidence of
      nonresponsiveness (NR) and high post-treatment platelet aggregation (post-PA).
      BACKGROUND: We have reported NR after a 300-mg loading dose. Limited information
      is available on the comparative effect of a 600-mg loading dose on the incidence
      of NR and high post-PA. METHODS: Clopidogrel responsiveness and post-PA were
      measured in patients undergoing stenting (n = 190) randomly treated with either a
      300-mg or a 600-mg clopidogrel load. Nonresponsiveness was defined as <10%
      absolute change in platelet aggregation, and high post-PA was defined as >75th
      percentile aggregation after 300 mg clopidogrel. RESULTS: Nonresponsiveness was
      lower after 600 mg compared to the 300-mg dose (8% vs. 28% and 8% vs. 32% with 5
      and 20 microM ADP, respectively, p < 0.001). Among the patients with high post-PA
      after 300 mg clopidogrel, 62% to 65% had NR, whereas after the 600-mg dose, all
      of the patients with high post-PA had NR. CONCLUSIONS: A 600-mg clopidogrel
      loading dose reduces the incidence of NR and high post-PA as compared to a 300-mg
      dose. Higher dosing strategies and methods to confirm platelet inhibition should
      be further investigated in order to optimally use clopidogrel in patients
      undergoing stenting.

PMID- 15862409
TI  - Prediction of mortality after primary percutaneous coronary intervention for
      acute myocardial infarction: the CADILLAC risk score.
AB  - OBJECTIVES: We sought to develop a simple risk score for predicting mortality
      after primary percutaneous coronary intervention (PCI) for acute myocardial
      infarction (AMI). BACKGROUND: Accurate risk stratification after primary PCI is
      important. Previous risk scores after reperfusion therapy have incorporated
      clinical +/- angiographic variables but have not considered baseline left
      ventricular function. Moreover, prior studies have not been validated against
      independent databases or studies. METHODS: The databases from the two largest
      multicenter, randomized AMI trials of primary PCI were utilized for score
      derivation (the Controlled Abciximab and Device Investigation to Lower Late
      Angioplasty Complications [CADILLAC] trial, n = 2,082) and subsequent validation
      (the Stent-Primary Angioplasty in Myocardial Infarction [Stent-PAMI] trial, n =
      900). Logistic regression and the jackknife procedure were used to select
      correlates of one-year mortality that were subsequently weighted and integrated
      into an integer scoring system. RESULTS: Seven variables selected from the
      initial multivariate model were weighted proportionally to their respective odds
      ratio for one-year mortality (age >65 years [2 points], Killip class 2/3 [3
      points], baseline left ventricular ejection fraction <40% [4 points], anemia [2
      points], renal insufficiency [3 points], triple-vessel disease [2 points], and
      post-procedural Thrombolysis In Myocardial Infarction flow grade [2 points]).
      Three strata of risk were defined (low risk, score 0 to 2; intermediate risk,
      score 3 to 5; and high risk, score >/=6) with excellent prognostic accuracy for
      survival in the derivation and validation sets (c statistics = 0.83 and 0.81 for
      30-day mortality and 0.79 and 0.78 for 1-year mortality, respectively).
      CONCLUSIONS: In AMI patients treated with primary PCI, seven risk factors readily
      available at the time of intervention accurately predict short- and long-term
      mortality. Of note, measurement of baseline left ventricular function is the
      single most powerful predictor of survival and should be incorporated into risk
      score models.

PMID- 15862410
TI  - High serum erythropoietin level is associated with smaller infarct size in
      patients with acute myocardial infarction who undergo successful primary
      percutaneous coronary intervention.
AB  - OBJECTIVES: We investigated whether a higher serum erythropoietin (EPO) level in
      patients with acute myocardial infarction (MI) subjected to successful primary
      percutaneous coronary intervention (PCI) can predict a smaller infarct size
      determined by creatine kinase (CK) release. BACKGROUND: Erythropoietin has been
      shown to protect cardiomyocytes from ischemia-reperfusion injury in rodents.
      METHODS: We prospectively studied 101 patients with first MI who received
      successful primary PCI within 12 h from the onset of MI. Blood samples were
      collected to examine the serum EPO level after the primary PCI and within 24 h
      from the onset of MI. RESULTS: The peak CK level and cumulative CK release were
      significantly lower in the above-median EPO group than in the below-median EPO
      group. Thrombolysis In Myocardial Infarction (TIMI) grades and collateral grades
      before PCI, infarct-related coronary arteries, time to the successful reperfusion
      from the onset of MI, and serum creatinine levels were similar in the two EPO
      groups. A stepwise multiple regression analysis revealed that the absolute serum
      EPO level (mU/ml) as well as TIMI grades after PCI and preinfarction angina was
      an independent predictor for the cumulative CK release. CONCLUSIONS: These data
      suggest that a high endogenous EPO level can predict a smaller infarct size in
      patients with acute MI subjected to successful primary PCI. This might be
      attributed to the potentially protective effect of endogenous EPO against
      ischemia-reperfusion injury in humans.

PMID- 15862411
TI  - The gender-specific impact of diabetes and myocardial infarction at baseline and
      during follow-up on mortality from all causes and coronary heart disease.
AB  - OBJECTIVES: The goal of this study is to compare the magnitude of diabetes and
      myocardial infarction (MI) at baseline and during follow-up on cause-specific and
      all-cause mortality. BACKGROUND: History of both MI and diabetes are strong
      predictors of coronary heart disease (CHD) death. However, gender-specific data
      on the joint effect of diabetes and MI, and particularly on the effect of
      incident diabetes and MI developed during the follow-up, on CHD mortality are
      scarce. METHODS: The baseline cohort study included 2,416 patients with prior
      diabetes or MI at baseline; the follow-up cohort study included 4,315 patients
      with incident diabetes or MI diagnosed during the follow-up. RESULTS: In the
      baseline cohort study, men with prior MI had a 20% to 80% increased risk of CHD
      or total mortality, but women with prior MI had a 43% to 45% decreased risk of
      CHD or total mortality in comparison with men and women with prior diabetes. In
      the follow-up cohort study, men and women with incident MI had a higher risk of
      CHD mortality (hazard ratio [HR] 2.15 in men and 1.65 in women), and an almost
      similar risk of total mortality (HR 0.95 in men and 1.02 in women) in comparison
      with men and women with incident diabetes. CONCLUSIONS: In men, MI at baseline or
      during follow-up confers a greater risk on CHD mortality than diabetes does. In
      women, prior MI at baseline confers a lower risk on CHD mortality than prior
      diabetes does, but incident MI during follow-up confers a greater risk than
      incident diabetes does. In both men and women, total mortality is similar for
      incident MI and diabetes.

PMID- 15862412
TI  - Ventricular assist device therapy normalizes inducible nitric oxide synthase
      expression and reduces cardiomyocyte apoptosis in the failing human heart.
AB  - OBJECTIVES: We examined the effect of mechanical unloading with ventricular
      assist device (VAD) therapy on myocardial inducible nitric oxide synthase (iNOS)
      expression and cardiomyocyte apoptosis in patients with end-stage heart failure
      (HF). BACKGROUND: Despite advances in medical therapy, HF continues to be a
      progressive and ultimately fatal disorder. High levels of iNOS expression are
      present in the myocardium of failing hearts, suggesting a potential role for iNOS
      in HF progression. METHODS: Inducible NOS protein expression was analyzed by
      Western blotting and cardiomyocyte apoptosis by terminal
      deoxynucleotidyltransferase dUTP nick end-labeling (TUNEL) in myocardial samples
      from failing hearts. Included in these analyses were tissues from 9 patients at
      the time of transplantation (HF-transplant group), 10 patients at the time of VAD
      insertion (pre-VAD group), and 11 patients undergoing transplant after VAD
      support (post-VAD group). Seven control samples were obtained at autopsy.
      RESULTS: Low or undetectable levels of iNOS were present in controls (0.005 +/-
      0.002). The HF-transplant and pre-VAD myocardial specimens exhibited a marked
      increase in iNOS expression (1.48 +/- 0.34 and 1.29 +/- 0.26, respectively; p <
      0.01 for both vs. controls). The increase in iNOS expression was reversed in the
      post-VAD group (0.36 +/- 0.16; p < 0.01 vs. HF-transplant and pre-VAD groups).
      The rate of TUNEL-positive cardiomyocytes was high in the pre-VAD group and
      significantly lower in the post-VAD group (0.64 +/- 0.15% in pre-VAD group and
      0.16 +/- 0.07% in post-VAD group; p < 0.01). The iNOS levels correlated
      significantly with cardiomyocyte apoptosis (r = 0.66, p < 0.01). CONCLUSIONS:
      Therapy with VAD normalizes iNOS expression in association with diminished
      cardiomyocyte apoptosis in the failing heart. Further work is required to define
      whether a causal relationship exists between iNOS and cardiomyocyte apoptosis.

PMID- 15862413
TI  - Inducible nitric oxide synthase in severe human heart failure: impact of
      mechanical unloading.

PMID- 15862414
TI  - Effects of left ventricular assist device therapy on ventricular arrhythmias.
AB  - OBJECTIVES: In a retrospective study, we sought to evaluate the effect of left
      ventricular assist device (LVAD) therapy on ventricular tachyarrhythmias in
      patients with advanced congestive heart failure. BACKGROUND: Despite the
      increasing use of LVAD as a bridge to cardiac transplantation, our knowledge
      regarding its effect on ventricular arrhythmias is currently limited to small
      series. Little is known about the prevalence, predictors, and clinical
      consequences of ventricular arrhythmias in LVAD recipients. METHODS: We reviewed
      the pre- and post-LVAD course of the last 100 consecutive adult patients to
      receive a HeartMate LVAD (Thoratec Laboratories Corp., Pleasanton, California) at
      our institution. All ventricular arrhythmias sustained for at least 30 s or
      requiring defibrillation were analyzed. All documented pre- and post-LVAD
      sustained ventricular arrhythmias were classified either as monomorphic
      ventricular tachycardia (MVT) or polymorphic ventricular tachycardia
      (PVT)/ventricular fibrillation (VF). RESULTS: Our population had an average age
      of 51 years, had predominately ischemic cardiomyopathy (63%), and a mean left
      ventricular ejection fraction of 20 +/- 10%. New-onset MVT was observed in 18
      patients who did not have MVT before LVAD placement. After LVAD, new-onset MVT
      was 4.5 times more likely than elimination of previously present MVT (p = 0.001),
      whereas the effect of LVAD on incidence of PVT/VF was not significant. In a
      multivariate Cox proportional hazards regression analysis, serum electrolyte
      abnormality was an independent predictor of post-LVAD ventricular arrhythmias.
      Preoperative MVT did not predict postoperative MVT. CONCLUSIONS: After LVAD
      placement, there is a significant rise in the incidence of de novo MVT. By
      contrast, the incidence of PVT/VF was unaffected by LVAD placement.

PMID- 15862415
TI  - Left ventricular assist device malfunction: an approach to diagnosis by
      echocardiography.
AB  - OBJECTIVES: A protocol using transthoracic echocardiography was designed to
      diagnose the common malfunctions of patients on chronic support with a left
      ventricular assist device (LVAD). BACKGROUND: Mechanical circulatory support,
      primarily with a LVAD, is increasingly used for treatment of advanced heart
      failure as a bridge to transplant and for long-term treatment of heart failure.
      The LVAD dysfunction is a recognized complication. To date, no studies have
      defined the role of transthoracic echocardiography in evaluating long-term
      mechanical complications of chronic LVAD support. METHODS: Transthoracic
      echocardiography was used in a protocol designed to detect the common types of
      mechanical malfunction. Patients were followed up with serial echocardiograms,
      and clinical validations were made with findings from a catheter-based protocol
      and inspection at the time of cardiac transplant or corrective surgery. RESULTS:
      Thirty-two patients with 44 LVADs were followed up during a four-year period
      using this protocol that correctly identified 11 patients with inflow valve
      regurgitation, 2 with intermittent inflow conduit obstruction, 1 with severe
      kinking of the outflow graft, and 9 with new insufficiency of the native aortic
      valve. CONCLUSIONS: As LVAD use for end-stage heart failure becomes widespread,
      and durations of support are extended, dysfunction will be increasingly
      prevalent. Transthoracic echocardiography provides a practical method to
      accurately identify the causes of mechanical dysfunction with patients on chronic
      LVAD support.

PMID- 15862416
TI  - Impaired progenitor cell activity in age-related endothelial dysfunction.
AB  - OBJECTIVES: We investigated whether human age-related endothelial dysfunction is
      accompanied by quantitative and qualitative alterations of the endothelial
      progenitor cell (EPC) pool. BACKGROUND: Circulating progenitor cells with an
      endothelial phenotype contribute to the regeneration and repair of the vessel
      wall. An association between the loss of endothelial integrity and EPC
      modification may provide a background to study the mechanistic nature of such age
      related vascular changes. METHODS: In 20 old and young healthy individuals (61 +/
      2 years and 25 +/- 1 year, respectively) without major cardiovascular risk
      factors, endothelial function, defined by flow-mediated dilation of the brachial
      artery via ultrasound, as well as the number and function of EPCs isolated from
      peripheral blood, were determined. RESULTS: Older subjects had significantly
      impaired endothelium-dependent dilation of brachial artery (flow-mediated
      dilation [FMD] 5.2 +/- 0.5% vs. 7.1 +/- 0.6%; p < 0.05). Endothelium-independent
      dilation after glycerol trinitrate (GTN) was not different, but the FMD/GTN ratio
      was significantly lower in old subjects (49 +/- 4% vs. 37 +/- 3%; p < 0.05),
      suggesting endothelial dysfunction. There were no differences in the numbers of
      circulating EPCs, defined as CD34/KDR or CD133/KDR double-positive cells in
      peripheral blood. In contrast, lower survival (39 +/- 6 cells/mm(2) vs. 65 +/- 11
      cells/mm(2); p < 0.05), migration (80 +/- 12 vs. 157 +/- 16 cells/mm(2); p <
      0.01), and proliferation (0.20 +/- 0.04 cpm vs. 0.44 +/- 0.07 cpm; p < 0.05)
      implicate functional impairment of EPCs from old subjects. The FMD correlated
      univariately with EPC migration (r = 0.52, p < 0.05) and EPC proliferation (r =
      0.49, p < 0.05). Multivariate analysis showed that both functional features
      represent independent predictors of endothelial function. CONCLUSIONS:
      Maintenance of vascular homeostasis by EPCs may be attenuated with age based on
      functional deficits rather than depletion of CD34/KDR or CD133/KDR cells.

PMID- 15862417
TI  - Circulating endothelial progenitor cells are reduced in peripheral vascular
      complications of type 2 diabetes mellitus.
AB  - OBJECTIVES: We sought to establish whether a reduction in endothelial progenitor
      cells (EPCs) has a putative role in peripheral vascular disease (PVD) of type 2
      diabetic patients. BACKGROUND: Peripheral vascular disease is a common and severe
      complication of diabetes mellitus. Impaired collateralization of diabetic
      vasculopathy has been extensively shown, but causes leading to its pathogenesis
      are not fully understood. Recently, EPCs have been found to contribute to
      vascular repair and angiogenesis. Diabetes has been associated with low levels of
      circulating EPCs, but no data are available in the literature on the relationship
      between EPCs and PVD in diabetes. METHODS: Flow cytometric analysis was used to
      quantify circulating progenitor cells (CPCs, CD34+) and EPCs (CD34+KDR+) in 51
      patients and 17 control subjects. RESULTS: The CPCs and EPCs from diabetic
      patients were reduced by 33% and 40%, respectively, compared with healthy
      subjects (p < 0.001). An inverse correlation was found between the number of EPCs
      and the values of fasting glucose (r = -0.49, p = 0.006). Peripheral vascular
      disease was associated with a 47% reduction in EPCs (p < 0.0001) and EPC levels
      directly correlated with the ankle-brachial index (r = 0.70, p = 0.01). The
      subgroup of diabetic patients with PVD also had reduced CPCs by 32% (p = 0.037),
      whereas patients with ischemic foot lesions had the lowest levels of both EPCs
      and CPCs (p = 0.02). CONCLUSIONS: Our data demonstrate decreased EPC levels in
      diabetic patients and, for the first time, show that PVD is associated with an
      extensively low number of EPCs. Depletion of circulating EPCs in diabetic
      patients may be involved in the pathogenesis of peripheral vascular
      complications.

PMID- 15862418
TI  - Endothelial progenitor obsolescence and atherosclerotic inflammation.

PMID- 15862419
TI  - Increased ambulatory pulse pressure is a strong risk factor for coronary
      endothelial vasomotor dysfunction.
AB  - OBJECTIVES: This study was aimed to determine the relationship between pulse
      pressure (PP) and coronary vasomotor dysfunction, a predictor of coronary events.
      BACKGROUND: Pulse pressure is a strong risk factor for coronary artery disease
      (CAD). However, the mechanisms by which an increase in PP affects the
      pathogenesis of CAD are unclear. METHODS: Ambulatory blood pressure (BP)
      monitoring for 24 h was performed in 103 consecutive patients with normal
      coronary angiograms (51 hypertensive and 52 normotensive; age 42 to 70 years).
      The relationship between changes in coronary arterial diameter and blood flow
      during an intracoronary infusion of acetylcholine (ACh) (5, 10, 50 microg/min),
      and BP parameters, and other traditional risk factors was evaluated using
      univariate and multivariate linear regression analyses. RESULTS: With
      multivariate analyses, the 24-h PP showed an inverse correlation with the
      epicardial coronary dilator response to ACh independently of other covariates
      including age, smoking, and 24-h systolic BP in normotensive as well as
      hypertensive patients. Furthermore, multivariate analysis showed that the 24-h PP
      was inversely and independently correlated with the increase in coronary blood
      flow in response to ACh. The dilator response of epicardial coronary arteries to
      nitrate was not significantly correlated with 24-h PP. CONCLUSIONS: Increased 24
      h PP is independently associated with endothelial vasomotor dysfunction in
      conduit and resistance coronary arteries irrespective of the presence of
      hypertension. Increased ambulatory PP may have an intimate relation to coronary
      endothelial vasomotor dysfunction.

PMID- 15862421
TI  - Relationship between inflammation and venous thromboembolism as studied by
      microparticle assessment in plasma.

PMID- 15862420
TI  - Elevation of endothelial microparticles, platelets, and leukocyte activation in
      patients with venous thromboembolism.
AB  - OBJECTIVES: The purpose of this research was to determine the levels of platelet,
      leukocyte, and endothelial activation and markers of cellular interactions in
      patients with venous thromboembolism (VTE). BACKGROUND: The details of
      interactions between endothelium, platelets, and leukocytes in VTE are not well
      understood. METHODS: We studied 25 patients with VTE and compared 25 healthy
      controls. We used flow cytometry to measure: 1) endothelial microparticles (EMP)
      identified by CD31+/CD42b- (EMP(31)) or E-selectin (EMP(62E)); 2) platelet
      microparticles (CD31+/CD42b+); 3) surface expression of P-selectin in platelets
      and CD11b in leukocytes; 4) EMP-monocyte conjugates (percentage of monocytes
      positive for E-selectin); and 5) platelet-leukocyte conjugates (PLC) expressed as
      percentage of leukocytes positive for CD41. RESULTS: Patients with VTE had marked
      elevations of EMP(31) (2,193 vs. 383 counts/microl; p = 0.003), EMP(62E) (368 vs.
      223 counts/microl; p = 0.001), and EMP-monocyte conjugates (3.3% vs. 2.5%; p =
      0.002), as well as increased activation of platelets (35.2 vs. 5.0 fluorescence
      intensity units for P-selectin; p < 0.0001) and leukocytes (13.9 vs. 7.7 U for
      CD11b; p = 0.004). Also elevated in VTE were PLC (61.7% vs. 39.6%; p = 0.01).
      Expression of CD11b in leukocytes strongly correlated with PLC (r = 0.74; p <
      0.0001). CONCLUSIONS: Marked activation of endothelium, platelets, and leukocytes
      occurs in VTE, and VTE, or the accompanying inflammatory process, involves the
      release of EMP and formation of EMP-monocyte conjugates and PLC. These findings
      support prior studies suggesting that release of EMP and their binding to
      monocytes are key events in thrombogenesis. Our findings also support the concept
      that the formation of PLC regulates leukocyte activation and participates in
      linking thrombosis with inflammation.

PMID- 15862422
TI  - Mortality reduction by implantable cardioverter-defibrillators in high-risk
      patients with heart failure, ischemic heart disease, and new-onset ventricular
      arrhythmia: an effectiveness study.
AB  - OBJECTIVES: To investigate the generalizability of the reduction in mortality
      posed by implantable cardioverter-defibrillators, we examined the effectiveness
      of defibrillators as applied in routine medical practice. BACKGROUND: Implantable
      cardioverter-defibrillators have been shown to be efficacious in the primary and
      secondary prevention of overall and cardiovascular mortality in clinical trials.
      METHODS: Using the National Veterans Administration database, we identified a
      cohort of 6,996 patients from 1995 to 1999 with new-onset ventricular arrhythmia
      and pre-existing ischemic heart disease and congestive heart failure, of which
      1,442 received a defibrillator, and followed them for three years to determine
      rates of mortality. With multivariate logistic regression analyses that adjusted
      for demographics, illness severity, and comorbidity, we assessed overall,
      cardiovascular, and noncardiovascular rates of mortality. To further address
      potential confounding, we also stratified the cohort by quintiles using a
      multivariable propensity score for each patient and determined mortality rates.
      RESULTS: For the overall cohort, multivariate regression showed that those who
      received defibrillators had significantly lower all-cause (odds ratio [OR] 0.52;
      95% confidence interval [CI] 0.45 to 0.60) and cardiovascular (OR 0.56; 95% CI
      0.49 to 0.65)] rates of mortality at three years. No significant differences were
      noted between groups in their rates of noncardiovascular mortality (OR 0.92; 95%
      CI 0.77 to 1.10). Propensity score analysis demonstrated similar mortality
      reduction benefits at three years: risk ratio (RR) 0.72 (95% CI 0.69 to 0.79) for
      all-cause; RR 0.70 (95% CI 0.63 to 0.78) for cardiovascular; and RR 0.95 (95% CI
      0.83 to 1.08) for noncardiovascular rates of mortality. These results suggest
      that one death is prevented in this patient population for every four to five
      patients receiving a defibrillator for three years. CONCLUSIONS: Implantable
      cardioverter-defibrillators in routine medical practice significantly reduce
      cardiovascular and all-cause rates of mortality at levels similar to secondary
      prevention trials.

PMID- 15862424
TI  - Focal atrial tachycardia from the ostium of the coronary sinus:
      electrocardiographic and electrophysiological characterization and radiofrequency
      ablation.
AB  - OBJECTIVES: The goal of this study was to characterize the electrocardiographic
      and electrophysiologic features and frequency of focal atrial tachycardia (AT)
      originating from the coronary sinus ostium (CS). BACKGROUND: The ostium of the
      coronary sinus has been described as a site of origin of AT, but detailed
      characterization of these tachycardias is limited. METHODS: Thirteen patients
      (6.7%) of 193 undergoing radiofrequency ablation (RFA) for focal AT are reported.
      Endocardial activation maps (EAM) were recorded from catheters at the CS (10
      pole), crista terminalis (20 pole), and His positions. The P waves were
      classified negative, positive, isoelectric, or biphasic. RESULTS: The mean age
      was 41 +/- 6 years, seven female patients, with symptoms for 8 +/- 3 years.
      Tachycardia was induced by programmed extra-stimuli in eight patients, was
      spontaneous in three patients, and in response to isoproterenol in two patients.
      These foci had a characteristic P-wave morphology. At the CS ostium, the P-wave
      was deeply negative in all inferior leads, negative or isoelectric becoming
      positive in lead V(1), then progressively negative across the precordium. Lead
      aVL was positive in all patients. Earliest EAM activity occurred at the proximal
      CS at 20 +/- 3 ms ahead of P-wave. Mean activation time at the successful RFA
      site = -36 +/- 8 ms; RFA was acutely successful in 11 of 13 patients. Long-term
      success was achieved in 11 of 11 over a median follow-up of 25 +/- 4 months.
      CONCLUSIONS: The CS ostium is an uncommon site of origin for focal AT (6.7%). It
      can be suspected as a potential anatomic site of AT origin from the
      characteristic P-wave and activation timing. Long-term success was achieved with
      focal ablation in the majority of patients.

PMID- 15862423
TI  - Right atrial pacing impairs cardiac function during resynchronization therapy:
      acute effects of DDD pacing compared to VDD pacing.
AB  - OBJECTIVES: We aimed to compare the hemodynamic effects of right-atrial-paced
      (DDD) and right-atrial-sensed (VDD) biventricular paced rhythm on cardiac
      resynchronization therapy (CRT). BACKGROUND: Cardiac resynchronization therapy
      improves hemodynamics in patients with severe heart failure and left ventricular
      (LV) dyssynchrony. However, the impact of active right atrial pacing on
      resynchronization therapy is unknown. METHODS: Seventeen CRT patients were
      studied 10 months (range: 1 to 46 months) after implantation. At baseline, the
      programmed atrioventricular delay was optimized by timing LV contraction properly
      at the end of atrial contraction. In both modes the acute hemodynamic effects
      were assessed by multiple Doppler echocardiographic parameters. RESULTS: Compared
      to DDD pacing, VDD pacing resulted in much better improvement of intraventricular
      dyssynchrony assessed by the septal-to-posterior wall motion delay (VDD 106 +/-
      83 ms vs. DDD 145 +/- 95 ms; p = 0.001), whereas the interventricular mechanical
      delay (difference between onset of pulmonary and aortic outflow) did not differ
      (VDD 20 +/- 21 ms vs. DDD 18 +/- 17 ms; p = NS). Furthermore, VDD pacing
      significantly prolonged the rate-corrected LV filling period (VDD 458 +/- 123 ms
      vs. DDD 371 +/- 94 ms; p = 0.0001) and improved the myocardial performance index
      (VDD 0.60 +/- 0.18 vs. DDD 0.71 +/- 0.23; p < 0.01). CONCLUSIONS: Our findings
      suggest that avoidance of right atrial pacing results in a higher degree of LV
      resynchronization, in a substantial prolongation of the LV filling period, and in
      an improved myocardial performance. Thus, the VDD mode seems to be superior to
      the DDD mode in CRT patients.

PMID- 15862425
TI  - Ethnic differences in the prognostic value of stress technetium-99m tetrofosmin
      gated single-photon emission computed tomography myocardial perfusion imaging.
AB  - OBJECTIVES: This study was designed to evaluate the differential prognostic value
      of gated single-photon emission computed tomographic imaging (SPECT) imaging in
      an ethnically diverse multicenter registry. BACKGROUND: Ethnic minority patient
      populations have reportedly higher coronary heart disease mortality with greater
      comorbidity and a clustering of risk factors at a significantly younger age when
      compared with Caucasian, non-Hispanic patients. Despite our increasingly diverse
      population, the predictive accuracy of cardiac imaging in ethnic minority
      patients is ill-defined. METHODS: A total of 7,849 patients were prospectively
      enrolled in a registry of patients undergoing exercise (44%) or pharmacologic
      stress (56%) technetium-99m tetrofosmin SPECT. Scans were scored using a 20
      segment myocardial model with a 5-point severity index. Multivariable Cox
      proportional hazards models were employed to assess time to death or myocardial
      infarction. RESULTS: A total of 1,993 African-American, 464 Hispanic, and 5,258
      Caucasian non-Hispanic patients underwent SPECT imaging. African-American and
      Hispanic patients more often had a history of stroke, peripheral arterial
      disease, angina, heart failure, diabetes, hypertension, and smoking at a younger
      age. Moderate or severely abnormal SPECT scans were noted in 21%, 17%, and 13% of
      African-American, Hispanic, and Caucasian non-Hispanic patients, respectively (p
      < 0.0001). Cardiovascular death rates were highest for ethnic minority patients
      (p < 0.0001). Annual rates of ischemic heart disease death ranged from 0.2% to
      3.0% for Caucasian non-Hispanic and 0.8% to 6.5% for African-American patients
      with low-risk to severely abnormal SPECT scans (p < 0.0001). For post-stress
      ejection fraction <45%, annualized risk-adjusted death rates were 2.7% for
      Caucasian non-Hispanic patients versus 8.0% and 14.0% for African-American and
      Hispanic patients (p < 0.0001). CONCLUSIONS: The current results from a large
      observational registry reveal that exercise and pharmacologic stress SPECT
      effectively predicts major cardiovascular events in a large cohort of African
      American and Hispanic patients evaluated for suspected myocardial ischemia. These
      results provide further evidence that ethnic minority patient populations have a
      worsening outcome related to cardiovascular disease.

PMID- 15862426
TI  - Positron emission tomography-measured abnormal responses of myocardial blood flow
      to sympathetic stimulation are associated with the risk of developing
      cardiovascular events.
AB  - OBJECTIVES: We sought to assess prospectively whether patients with normal
      coronary angiograms but with impaired myocardial blood flow (MBF) increases to
      cold pressor testing (CPT) are at increased risk for cardiovascular events.
      BACKGROUND: Invasive angiographic assessments of coronary vasomotor function have
      demonstrated an impairment of endothelium-related coronary flow increases to
      independently predict future cardiovascular events. It is unknown whether
      noninvasive positron emission tomography (PET)-measured MBF alterations to
      sympathetic stimulation with CPT are associated with the risk of developing
      cardiovascular events. METHODS: A total of 72 patients (44 men, 28 women, age 58
      +/- 8 years) referred for diagnostic cardiac catheterization were studied.
      Myocardial blood flow was measured in absolute units with (13)N-ammonia using
      PET, at baseline and during CPT in each patient. Cardiovascular events
      (cardiovascular death, acute coronary syndrome, myocardial infarction,
      percutaneous transluminal coronary angioplasty, coronary artery bypass grafting,
      ischemic stroke, or peripheral revascularization) were assessed as clinical
      outcome parameters over a mean follow-up period of 66 +/- 8 months. Patients were
      assigned to three groups: group 1, patients with >/=40% increase in MBF
      (%DeltaMBF), n = 22; group 2, patients with >0 and <40% increases in MBF, n = 32;
      and group 3, patients with decreases in MBF (</=0%), n = 18. RESULTS: During
      follow-up, one of the group 1 patients developed a cerebral stroke. In group 2,
      15 cardiovascular events occurred in 9 patients and in group 3, 7 patients
      experienced 9 cardiovascular events (p </= 0.0001, univariate by log-rank test).
      Impaired MBF increases in group 2 and group 3 were associated with a
      significantly higher incidence of cardiovascular events by Kaplan-Meier analysis
      (p = 0.033, log-rank test). After adjusting for known coronary risk factors, MBF
      responses to CPT revealed a nonsignificant trend to be independently associated
      with a higher incidence for cardiovascular events (p = 0.065, multivariate by Cox
      regression model). CONCLUSIONS: Noninvasive PET-measured impaired MBF increases
      to sympathetic stimulation are associated with the risk of developing
      cardiovascular events.

PMID- 15862427
TI  - Cardiovascular manifestations of moderate to severe carbon monoxide poisoning.
AB  - OBJECTIVES: We describe the cardiovascular manifestations of carbon monoxide (CO)
      poisoning. BACKGROUND: Carbon monoxide poisoning is a common cause of toxicologic
      morbidity and mortality. Although the neurologic sequelae of CO poisoning have
      been well described, the cardiovascular consequences are limited to isolated case
      reports. METHODS: We reviewed the cardiovascular manifestations of 230
      consecutive patients treated for moderate to severe CO poisoning in the
      hyperbaric oxygen chamber at Hennepin County Medical Center (HCMC), a regional
      center for treatment of CO poisoning. RESULTS: The mean age was 47.2 years with
      72% men. Ischemic electrocardiogram (ECG) changes were present in 30% of
      patients, whereas only 16% had a normal ECG. Cardiac biomarkers (creatine kinase
      MB fraction or troponin I) were elevated in 35% of patients. In-hospital
      mortality was 5%. CONCLUSIONS: Cardiovascular sequelae of CO poisoning are
      frequent, with myocardial injury assessed by biomarkers or ECG in 37% of
      patients. Patients admitted to the hospital with CO poisoning should have a
      baseline ECG and serial cardiac biomarkers.

PMID- 15862428
TI  - The year in cardiovascular surgery.

PMID- 15862429
TI  - Intraoperative crossover: the well-kept surgical secret to apparent surgical
      success.
AB  - Cardiologists and patients contemplate the risk of proposed operations. Surgeons
      typically report outcomes on operations performed. Emergency intraoperative
      crossover from off- to on-pump coronary artery bypass grafting occurs uncommonly
      but has substantial rates of mortality and morbidity. Much of the reported
      perioperative benefit of off- compared with on-pump coronary artery bypass
      grafting is erased if data are presented by intention to treat and not by
      operation performed. Cardiologists and cardiac surgeons should share the
      responsibility for advising a patient to consent to a cardiac operation using
      honestly presented evidence of potential benefits and risks substantiated with
      information analyzed in patient-centric and not physician-centric ways.

PMID- 15862430
TI  - Multicenter intravascular ultrasound validation study among heart transplant
      recipients: outcomes after five years.
AB  - OBJECTIVES: We sought to assess the validity of first-year intravascular
      ultrasound (IVUS) data as a surrogate marker for long-term outcome after heart
      transplantation. BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major
      impediment to long-term graft survival. Intravascular ultrasound is more
      sensitive than coronary angiography and detects intimal thickening (early CAV) in
      the coronary arteries of the donor heart. Single-center studies have suggested
      first-year IVUS results might be a surrogate marker for long-term outcome.
      METHODS: First-year IVUS results and subsequent five-year clinical follow-up data
      were reviewed in 125 heart transplant recipients from five institutions. The IVUS
      tapes (at baseline and one year) were re-analyzed at a core IVUS laboratory. The
      change in maximal intimal thickness (MIT) from baseline to one year was recorded
      for several matched sites in the same coronary artery. Patients were classified
      into two groups: those with >/=0.5 mm in the MIT in any matched site (group 1)
      and those with MIT <0.5 mm (group 2). RESULTS: Group 1 patients compared with
      group 2 patients had a higher incidence of death or graft loss (D/GL, 20.8% vs.
      5.9%; p = 0.007), had more nonfatal major adverse cardiac events and/or D/GL
      (45.8% vs. 16.8%; p = 0.003), and had more findings of newly occurring
      angiographic luminal irregularities (65.2% vs. 32.6%, p = 0.004). CONCLUSIONS:
      This multicenter study suggests that progression of intimal thickening >/=0.5 mm
      in the first year after transplantation appears to be a reliable surrogate marker
      for subsequent mortality, nonfatal major adverse cardiac events, and development
      of angiographic CAV through five years after heart transplantation.

PMID- 15862431
TI  - Intravascular ultrasound evidence of angiographically silent progression in
      coronary atherosclerosis predicts long-term morbidity and mortality after cardiac
      transplantation.
AB  - OBJECTIVES: The aim of this study was to determine whether angiographically
      silent early coronary intimal thickening could predict long-term morbidity and
      mortality. BACKGROUND: Although intravascular ultrasound (IVUS) is widely used to
      detect early transplant coronary disease, its prognostic significance has not
      been well defined. METHODS: The study cohort consisted of 143 patients who
      underwent early multivessel (2.1 +/- 0.7 arteries/patient) IVUS examination 1.0
      +/- 0.5 month and 12.0 +/- 1.0 month after transplantation. The change in intimal
      thickness was evaluated using paired analysis of 1,069 matched sites. Rapidly
      progressive vasculopathy was defined as the change in intimal thickness >/=0.5
      mm. Patients were followed for a primary end point of all-cause mortality and a
      secondary composite end point of mortality and nonfatal myocardial infarction
      (MI). Angiographic disease, defined as any >/=50% diameter stenosis, was assessed
      in 126 patients. RESULTS: Intravascular ultrasound at one year demonstrated rapid
      progression in 54 (37%) of 143 patients and new lesions in 67 (47%) of 143 of
      patients. At a mean clinical follow-up of 5.9 years, more patients with rapidly
      progressive vasculopathy died, as compared with those without (26% vs. 11%, p =
      0.03). Death and MI also occurred more frequently among those with rapid
      progression than in those without it (51% vs. 16%, p < 0.0001). There was no
      significant difference in outcome in patients with and without donor-transmitted
      lesions. Angiographic disease was found in 11 (22%) of 50 patients with and in 2
      (2.1%) of 76 patients without (p = 0.003) rapidly progressive vasculopathy. The
      IVUS-defined rapid progression correlated highly with future development of
      angiographic disease (p = 0.0005). CONCLUSIONS: Rapidly progressive vasculopathy
      by IVUS, defined as an increase of >/=0.5 mm in intimal thickness within the
      first year after transplantation, is a powerful predictor of all-cause mortality,
      MI, and angiographic abnormalities. Accordingly, such patients may be candidates
      for more aggressive anti-atherosclerotic and/or immunosuppressive therapy.

PMID- 15862433
TI  - Prodromal angina limits infarct size in the setting of acute anterior myocardial
      infarction treated with primary percutaneous intervention.

PMID- 15862434
TI  - Gender differences in endothelial tissue-type plasminogen activator release in
      middle-aged adults.

PMID- 15862435
TI  - Further aspects of anemia, heart failure, and erythropoietin.

PMID- 15862436
TI  - Is there an optimal hematocrit value for cardiac patients?

PMID- 15862438
TI  - Conflation of empiric and nonempiric truths in cardiovascular guidelines.

PMID- 15862440
TI  - Omega-3 fatty acids for secondary prevention.

PMID- 15862441
TI  - The clinical development of percutaneous heart valve technology: a position
      statement of the Society of Thoracic Surgeons (STS), the American Association for
      Thoracic Surgery (AATS), and the Society for Cardiovascular Angiography and
      Interventions (SCAI) Endorsed by the American College of Cardiology Foundation
      (ACCF) and the American Heart Association (AHA).

PMID- 15862442
TI  - Anaerobic ammonium oxidation (anammox) in the marine environment.
AB  - Anammox, anaerobic ammonium oxidation with nitrite, is now recognized as an
      important process in the marine nitrogen cycle. The bacteria conducting anammox
      are highly specialized and appear to belong to the Planctomycetales. The process
      has now been found in a range of environments including marine sediments, sea ice
      and anoxic water columns, and it may be responsible for up to 50% of the global
      removal of fixed nitrogen from the oceans.

PMID- 15862443
TI  - Sensitivity to potassium tellurite of Escherichia coli cells deficient in CSD,
      CsdB and IscS cysteine desulfurases.
AB  - The csdA, csdB and iscS genes encoding for cysteine desulfurase enzymatic
      activities in Escherichia coli were independently inactivated and potassium
      tellurite sensitivity, determined for each of the resulting mutant clones, was
      found to be iscS > csdB > csdA. Structural genes encoding for each of the wild
      type cysteine desulfurases were cloned into a vector containing the regulated ara
      promoter and further introduced into the mutant strains. Desulfurase-deficient
      cells transformed with homolog or paralog desulfurase genes and grown in
      arabinose-amended media restored their basal tellurite resistance. While csdB
      gene complemented the auxotrophy of csdB and iscS mutants for nicotinic acid, the
      iscS gene only complemented the auxotrophy of iscS cells for thiamine.
      Introduction of the csdA gene into the desulfurase-deficient strains did not
      change tellurite resistance or nutritional requirement patterns of the recipient
      cells. Complementation analysis could not be performed under anaerobic conditions
      because the three mutants did not show tellurite hypersensitivity. These results
      indicate that oxidative stress is involved in tellurite toxicity in E. coli.

PMID- 15862444
TI  - The product of the qacC gene of Staphylococcus epidermidis CH mediates resistance
      to beta-lactam antibiotics in gram-positive and gram-negative bacteria.
AB  - We have characterized a natural isolate of Staphylococcus epidermidis resistant
      to heavy metals that carries a small 2391-bp plasmid, pSepCH, encoding the qacC
      gene. The S. epidermidis qacC gene confers resistance to a number of beta-lactam
      antibiotics and to ethidium bromide in its natural host and in Escherichia coli
      K12 and Salmonella enterica sv. Typhimurium. This is the first communication of a
      small multidrug resistance (SMR) pump involved in resistance to beta-lactam
      antibiotics. Experiments using tolC, ompW and ompD mutant strains of S.
      Typhimurium demonstrated that the beta-lactam antibiotic resistance conferred by
      this pump does not depend on these outer membrane proteins.

PMID- 15862445
TI  - Purification and characterization of a protease produced by an aerobic
      haloalkaliphilic species belonging to the Salinivibrio genus.
AB  - An extracellular protease produced at the end of the exponential growth phase was
      purified to homogeneity and characterized from the new isolate haloalkaliphilic
      strain 18AG, phylogenetically related to Salinivibrio costicola subsp. costicola.
      The protease molecular mass was about 38 kDa. The enzyme was dependent on salt
      concentration for activity and stability, and it showed optimal activity at 60
      degrees C in the presence of 2.0% NaCl and 2.0 mM CaCl2, while in the absence of
      CaCl2 the optimum temperature was 50 degrees C. The enzyme was stable for 24 h at
      30 degrees C, whereas at 50 degrees C in the presence of CaCl2 the half life was
      about 5 h. The enzyme had an optimum pH of 8.0 with 80% of residual activity at
      pH 9.0. The protease was strongly inhibited by phenylmethyl sulfonylfluoride
      (PMSF), slightly activated by denaturing agents such as SDS and urea, and
      partially inhibited by thiol-containing reducing agents. The synthesis of the
      enzyme in culture media was influenced by the medium composition: it was
      specifically dependent upon the NaCl concentration and was induced by the
      presence of gelatin.

PMID- 15862446
TI  - In vitro detection and characterisation of a polyphosphate synthesising activity
      in the yeast Candida humicola G-1.
AB  - An in vitro detectable polyphosphate-synthesising activity was characterised
      using two independent assay systems in extracts of the yeast Candida humicola G
      1. Its properties were similar to those of a range of bacterial polyphosphate
      kinase enzymes. PCR amplification of C. humicola genomic DNA using universal
      primers for bacterial polyphosphate kinase genes yielded a product whose
      translated sequence showed up to 34% amino acid similarity to the bacterial
      enzyme.

PMID- 15862447
TI  - Sulfate requirement for heterotrophic growth of "Ferroplasma acidarmanus" strain
      fer1.
AB  - Growth of the acidophilic archaeon, "Ferroplasma acidarmanus" strain fer1, in a
      laboratory medium (primary constituents, FeSO4 72 mM and 0.02% yeast extract) is
      minimal. A survey of the annotated genome revealed metabolic transporters for
      Ni2+, sugars, and amino acids. Accordingly, the concentration of yeast extract
      was increased to 0.1% and the addition of 2 mM Ni(NH4)2(SO4)2 significantly
      enhanced the cultivation of strain fer1. The maximum optical density in the
      modified fer1 medium (mfer) was OD(492)=0.27 with 10(10) viable cells/ml as
      determined by a most-probable-number method, which exceeds previously reported
      viable cells/ml by >100-fold. Strain fer1 displayed chemolithotrophic growth with
      Fe2+ in mfer containing 100 mM FeSO4 or FeCl2. In the absence of Fe2+,
      heterotrophic growth occurred with one of the following salts (100 mM): ZnSO4,
      MnSO4, MgSO4, (NH4)2SO4, or Fe2(SO4)3, and did not occur with (100 mM): ZnCl2,
      MnCl2, MgCl2, NH4Cl, or FeCl3. Escaping headspace gas from strain fer1 cultures
      formed a precipitate in a zinc acetate trap. Sulfide was absent in the
      precipitate but zinc and sulfur were detected. These data demonstrate that SO4 is
      required for heterotrophic growth of strain fer1 and may have a role in the
      global sulfur cycle.

PMID- 15862448
TI  - A cold-active extracellular metalloprotease from Pedobacter cryoconitis-
      production and properties.
AB  - An extracellular protease from Pedobacter cryoconitis, isolated from alpine
      cryoconite on glacier ice, was purified and characterized. Despite high cell
      densities at a temperature range of 1-25 degrees C, the optimum temperature for
      protease production was 15 degrees C. Maximum enzyme production was achieved when
      the strain was grown in a pH-neutral medium containing soybean meal, wheat flour
      and citrate over 72 h. The 27-kDa enzyme was a metalloprotease (sensitive to
      EDTA, EGTA and phenanthroline) and showed maximal activity towards azocasein at
      40 degrees C and pH 8. The protease was stable for 60 min at 20-30 degrees C,
      lost 50% of activity after 30 min at 40 degrees C, and was inactivated at 50
      degrees C, but was resistant to repeated freezing and thawing. Calcium ions had
      no protective effect against thermal denaturation. More than 80% of the maximum
      activity were retained at a pH in the range of 7-10. No activity loss was
      detected after 1 h at pH 7-9 and 20 degrees C, nor after 1 h of incubation with 3
      M urea or 0.1% perborate.

PMID- 15862450
TI  - Mycotoxin-producing and other fungi isolated from grapes for wine production,
      with particular emphasis on ochratoxin A.
AB  - Mycotoxins are toxic secondary metabolites produced by filamentous fungi that
      have been detected in food commodities, including grapes and wine. A survey was
      conducted to assess mycotoxin-producing fungi in grapes destined for wine
      production. The mycotoxigenic capacity of the isolates was tested in culture
      media. Grapes were analyzed by plating methods from 4 Portuguese wine-growing
      regions at 3 maturation stages (pea berry, early veraison and ripe berry) between
      2001 and 2003. From the 10,602 strains detected and identified, the most frequent
      genera were Cladosporium (25%), Alternaria (24%), Botrytis (15%), Penicillium
      (9%) and Aspergillus (8%). Most (92.0%) were non-mycotoxigenic or produced
      mycotoxins of unknown relevance to health. Potential producers of ochratoxin A
      (OTA) (Aspergillus niger aggregate, 5.4%, Aspergillus carbonarius, 0.6%) and
      trichothecenes (Fusarium spp., 0.4%; Trichothecium roseum, 0.8%) were the most
      frequent mycotoxigenic species isolated from grapes. OTA was detected in all
      cultures of A. carbonarius and 4% of A. niger aggregate strains. There was
      potential for OTA and trichothecene production in grapes by A. carbonarius and T.
      roseum, respectively, prior to harvest time. Data presented herein indicate that
      A. carbonarius is most likely to occur in vineyards with Mediterranean climates,
      while T. roseum is more likely to occur in more temperate climates, and is
      associated with gray rot. The present work emphasizes the need to use grapes
      under good condition so as to reduce the risk of contamination with mycotoxigenic
      fungi and subsequent mycotoxin occurrence in wine.

PMID- 15862449
TI  - Quantitative analysis of adhesion and biofilm formation on hydrophilic and
      hydrophobic surfaces of clinical isolates of Staphylococcus epidermidis.
AB  - Staphylococcus epidermidis is now well established as a major nosocomial pathogen
      associated with infections of indwelling medical devices. The major virulence
      factor of these organisms is their ability to adhere to devices and form
      biofilms. However, it has not been established that adherence and biofilm
      formation are closely linked phenotypes for clinical isolates. In this study, the
      initial adhesion to different materials (acrylic and glass) of 9 clinical
      isolates of S. epidermidis, along with biofilm-positive and biofilm-negative
      control strains, was assayed using physico-chemical interactions to analyze the
      basis for bacterial adherence to the substratum. X-ray photo electron
      spectroscopy (XPS) analysis of the cell surface elemental composition was also
      performed in an attempt to find a relationship between chemical composition and
      adhesion capabilities. Biofilm formation on the two surfaces was evaluated by dry
      weight measurements. Human erythrocytes were used to evaluate the ability of S.
      epidermidis strains to cause hemagglutination, an indicator of the production of
      a poly-N-acetyl glucosamine cell surface polysaccharide also involved in biofilm
      formation. The clinical isolates exhibited different cell wall physico-chemical
      properties, resulting in differing abilities to adhere to surfaces. Adhesion to
      hydrophobic substrata for all strains occurred to a greater extent than that to
      hydrophilic surfaces. Bacterial cell hydrophobicity seemed to have little or no
      influence on adhesion. X-ray photoelectron spectroscopy analysis showed a high
      ratio of oxygen/carbon for all strains, which is a common characteristic of S.
      epidermidis species. No relevant relationship was found between XPS data and
      adhesion values. All strains forming biofilms were able to agglutinate
      erythrocytes. However, no direct relationship was found between the amount of
      biofilm formed and the initial adhesion extent. These results indicate that high
      levels of initial adherence do not necessarily lead to thick biofilm formation.
      These two aspects of the pathogenesis of medical device related-infection may
      need to be evaluated independently to ascertain the contribution of each to the
      virulence of S. epidermidis causing device-related infections.

PMID- 15862451
TI  - Isolation and identification of an EPS-producing Rhizobium strain from arid soil
      (Algeria): characterization of its EPS and the effect of inoculation on wheat
      rhizosphere soil structure.
AB  - The production of exopolysaccharides (EPSs) by bacterial populations in the
      rhizosphere has been demonstrated to contribute to water and nutrient uptake by
      plant roots through the modification of the physical properties of rhizosphere
      soil. We report here the characterization of a new EPS produced by a bacterial
      strain (KYGT207) isolated from an arid soil in southern Algeria (Gassi Touil),
      and the effect of inoculation of this strain on soil physical properties in the
      rhizosphere of Triticum durum L. Strain KYGT207 was assigned to the genus
      Rhizobium by 16S ribosomal DNA sequencing and belongs to a new species closely
      related to Rhizobium sullae. The EPS produced by this strain was found to be
      composed of glucose (Glc), galactose (Gal), and mannuronic acid (ManA) in a molar
      ratio of 2:1:1. The primary structure of the EPS was determined by sugar
      analysis, 1D and 2D NMR spectroscopy, consisting of a tetrasaccharide repeating
      unit with the following original structure: [structure: see text]. A rheological
      analysis showed that this EPS could be considered as a thickening agent with
      polyelectrolyte properties. Inoculation of wheat plantlets with strain KYGT207
      caused significant promotion of plant growth (+85% for shoot dry mass and +56%
      for root dry mass), a significant increase in root-adhering soil (RAS) dry mass
      (dm) per root dm (RAS/RT) up to 137%, and in RAS aggregate water stability. We
      demonstrate that EPS-producing bacteria were present in sandy soils subjected to
      water stress and that EPS-producing Rhizobium populations play an important role
      in the rhizosphere through their contribution to soil aggregation.

PMID- 15862452
TI  - Genetic diversity of noroviruses in raw and treated sewage water.
AB  - Human noroviruses cause gastroenteritis in humans, leading to high virus loads in
      sewage. Norovirus concentrations in raw and treated sewage samples from two
      sewage treatment plants (STP) were studied, along with virus removal and genetic
      diversity. Over one year, the average norovirus concentrations in raw sewage were
      approximately 10(5) pcr detectable units (pdu) per liter compared with 10(3)
      pdu/l of treated sewage. Similar sewage treatment processes at STP-A and STP-B
      led to 2.7 and 2.0 log(10)-units of virus removal, respectively. In total, 11
      different norovirus variants were detected in 49 out of 53 sewage samples, with
      up to four different norovirus strains in a single sewage sample. Along with
      GGI.6 Sindlesham and GGII.2 Melksham, the GGIIb variant was one of the most
      prevalent noroviruses in both raw and treated sewage. This strain emerged among
      populations in Europe in 2000 and 2001. Treated sewage containing 10(2)-10(3)
      norovirus pdu is discharged into the surface water. The use of such fecally
      contaminated surface waters for shellfish culture, drinking water production and
      recreational purposes poses a potential health risk. We showed the presence of
      multiple norovirus strains in raw and treated sewage, confirming the need to
      clone before sequencing the RT-PCR products. Exposure to multiple norovirus
      strains in sewage contaminated food or water may lead to the occurrence of
      norovirus recombinants, which may be more virulent and pathogenic than the
      norovirus strains already circulating in the population.

PMID- 15862453
TI  - Detection of Salmonella in environmental water and sediment by a nested-multiplex
      polymerase chain reaction assay.
AB  - From 1995 to 2002, 53 serovars of Salmonella were isolated in the Seine estuary
      (France). The 3 serovars most frequently found were S. enterica serovar
      Typhimurium, S. enterica serovar Infantis and S. enterica serovar Virchow. A
      nested multiplex PCR (nm-PCR) assay was developed to detect the presence of
      Salmonella in estuarine water and sediment samples. The target gene used was the
      phase 1 flagellin fliC chromosomal gene, present in all Salmonella serovars. A
      set of 4 primers was first used to amplify an 890-bp sequence of the fliC gene,
      and then a second set of 3 primers was used for the nested PCR. The nmPCR method
      has been successfully tested for 28 serovars, 13 of which are of epidemiological
      significance. The detection limit of the assay, without any pre-enrichment step,
      was estimated at 1 CFU in deionized water, and at 4-5 CFU in the reaction mixture
      when tested on estuarine water seeded with a Salmonella strain. When the nmPCR
      was used together with the classical culture method in environmental samples, it
      gave additional positive results for 11.3% of the sediment samples and 20% of the
      water samples despite a high background of other bacteria. Overall, the results
      demonstrated that this molecular approach informed us about the contamination by
      Salmonella of estuarine water and sediment samples. Positive amplifications
      suggested the presence of Salmonella DNA and could thus provide information about
      a recent (culturable) or past (non-culturable, released DNA) contamination of
      environmental samples by this pathogenic bacteria.

PMID- 15862454
TI  - Quantification of Staphylococcus aureus in unpasteurised bovine and caprine milk
      by real-time PCR.
AB  - A sensitive and reproducible real-time PCR assay targeting the nuc gene of
      Staphylococcus aureus was applied for quantification of this microorganism in
      artificially and naturally contaminated raw milk samples. The S. aureus cell
      equivalents (SCEs) estimated by the real-time PCR method were two log scales
      higher than colony forming units (CFUs) estimated from a plate count method in
      artificially contaminated milk. The repeatability of the real-time PCR assay
      including the DNA isolation procedure was assessed by analysing the data derived
      from naturally contaminated samples. The relative standard deviation of the log
      transformed data of four real-time PCR measurements including duplicate DNA
      isolations ranged between 11.3 and 1.0%. When analysing 80 bovine and 107 caprine
      naturally contaminated raw milk samples, the real-time PCR method yielded 19.3%
      more positive samples than the plate count method. With the exception of one
      sample, SCEs were always higher than CFUs. The difference between SCEs and CFUs
      was highly variable, and it was not possible to correlate real-time PCR-derived
      SCEs and CFUs. However, as each SCE detected by real-time PCR indicates a S.
      aureus cell, which is or has been present in the sample, this method offers the
      advantage of a retrospective analysis even of processed samples to aid food
      poisoning-related risk assessment.

PMID- 15862455
TI  - Rapid identification of Streptococcus pyogenes with PCR primers from a putative
      transcriptional regulator gene.
AB  - Streptococcus pyogenes (GAS) is a common bacterial pathogen that has emerged as
      an increasingly important health concern in many parts of the world. Although GAS
      may appear harmless in healthy individuals, the ability of this bacterium to take
      advantage of a weakened or compromised host defense system is extraordinary.
      Following the recent publication of the genome sequences of several S. pyogenes
      strains, we undertook an investigation of a specialized gene group in GAS that
      encodes transcriptional regulators. By screening S. pyogenes transcriptional
      regulator genes from the complete genome of M1 strain SF370 against other DNA
      sequences at GenBank by BLAST searches, we identified a gene (i.e., Spy1258) that
      is uniquely present in the bacterium. Application of PCR primers (spy1258F and
      spy1258R) derived from this gene facilitated amplification of a 407-bp DNA
      fragment from S. pyogenes only, but not from other species of the genus
      Streptococcus and common bacteria. Apart from offering an additional target for
      specific confirmation of GAS, further analysis of the putative transcriptional
      regulator gene Spy1258 and its related protein product may lead to new insights
      into the molecular mechanisms of S. pyogenes maintenance and pathogenicity.

PMID- 15862456
TI  - Evaluation of a PCR assay for the detection and identification of Campylobacter
      jejuni and Campylobacter coli in retail poultry products.
AB  - A PCR-based method was applied to Campylobacter detection in poultry samples at
      the retail level. In total, 73 retail poultry samples purchased from supermarkets
      in the Basque Country area in the north of Spain were examined using both culture
      and molecular (alternative) methods. In our routine method, the worldwide ISO
      10272:1995 standard of Preston broth incubated at 42 degrees C for conventional
      Campylobacter detection was adopted. The molecular method was comprised of a DNA
      extraction kit consisting of a single polypropylene spin column and PCR
      amplification of the Campylobacter 16S rRNA gene. A total of 54 raw samples were
      positive by either PCR or culture; among these, 50 were found to be positive by
      conventional plating and 54 by PCR. Concordant results, i.e., positive and
      negative in both methods, were found in 64 samples (94.1%). All positive samples
      by culture were also positive by PCR, resulting in 100% of positive concordance.
      Two samples (2.9%) positive after retesting by PCR were considered to be false
      negatives. The detection limit of the PCR method was 5 CFUs that corresponded to
      0.2 CFUs per 5 mul in the PCR mixture. The percentages of samples that required
      enrichment to prove Campylobacter presence were moderate, 18% by culture and 13%
      by PCR. Total analysis time was reduced to a few hours (within the working day)
      or 24 h when enrichment was required. Therefore, this PCR method proved to be
      useful as a routine diagnostic test for Campylobacter detection and confirmation
      of C. jejuni and C. coli in naturally contaminated poultry samples.

PMID- 15862457
TI  - M protein conserved region antibodies opsonise multiple strains of Streptococcus
      pyogenes with sequence variations in C-repeats.
AB  - The development of a group A streptococcal (GAS) vaccine has focused on the M
      protein, a major virulence factor. Antibodies against the amino terminal domain
      of the M protein are generally protective but only provide type-specific
      immunity. J14, a 29-mer peptide sequence which contains a conserved epitope from
      the C-repeat region of the M protein, offers the possibility of a vaccine which
      will elicit protective opsonic antibodies against multiple GAS strains. In this
      study we have shown that antibodies raised against J14 are capable of opsonising
      37 GAS isolates representing different emm types derived from a region in which
      GAS infection is endemic. We also demonstrate that J14 antisera is capable of
      opsonising GAS isolates containing J14 homologues but not J14-specific sequences,
      further increasing the strain coverage of this vaccine candidate. Isolates with
      three C-repeats were opsonised more efficiently than isolates with two repeats.
      Opsonisation of a strain with only a single C-repeat was dramatically lower than
      other strains tested. The number of C-repeats present in the M protein of
      individual isolates therefore appears to be the critical factor in determining
      bactericidal capacity of J14 antisera. The reduced opsonic capacity of sera
      against this strain was shown to correlate with a reduced capacity to bind J14
      antisera, as demonstrated by immunofluorescence microscopy and FACS analysis. In
      vivo challenge experiments also confirmed the protective efficacy of immunisation
      with J14 peptide.

PMID- 15862458
TI  - Hemagglutinating and hemolytic activities of Enterococcus faecalis strains
      isolated from different human clinical sources.
AB  - A total of 95 Enterococcus faecalis strains isolated from different human
      clinical sources were investigated for hemagglutinating activities and hemolysin
      (Hly) production in the presence of erythrocytes from a wide range of species.
      MRHA (mannose-resistant hemagglutination) activity was found in all clinical
      strains tested in this study. MRHA of E. faecalis strains isolated from different
      sources was most frequently observed with human (both group O and A) and guinea
      pig erythrocytes. None of the strains agglutinated horse erythrocytes in the
      presence of 1% alpha-D-mannose. It should be emphasized that our data indicate
      the absence of a relationship between sources and MRHA. In contrast, all 95
      strains investigated in this report were negative for MSHA (mannose-sensitive
      hemagglutination) activity. Regarding hemolysin production, it was seen that E.
      faecalis, and particularly urinary strains, preferably lysed horse erythrocytes.
      On the other hand, none of the 95 clinical strains tested in this study showed
      hemolytic activity against bovine and sheep erythrocytes. In general, these
      results show that E. faecalis strains isolated from different clinical sources
      possessed a diversity of hemagglutinins and a limited repertoire of hemolysin
      activities.

PMID- 15862459
TI  - Spoligotyping of Mycobacterium tuberculosis isolates from patients with pulmonary
      tuberculosis in Mumbai, India.
AB  - Tuberculosis remains a major health problem in India, with 2 million new cases
      and 421,000 deaths each year. In this paper, we describe the spoligotyping
      results of 216 Mycobacterium tuberculosis culture isolates from patients with
      pulmonary tuberculosis in Mumbai, India. As spoligotyping data from India have
      rarely been described until now, and as there is limited information on the major
      circulating clades of M. tuberculosis, the data obtained were also compared to an
      international spoligotype database (SpolDB4) that contained patterns from 22,546
      isolates from more than 100 countries. Eighty-four (39%) of the isolates were
      definitively marked as orphan strains, indicating the paucity of such data from
      India. The remaining 132 isolates clustered among 59 shared types; among these,
      42 shared types were already present in the database, 17 were newly created, and
      5 of them were specifically reported from Mumbai. A total of 9 major types in
      this study clustered 32% of the isolates. At the phylogenetic level, 30% of the
      isolates belonged to the Central Asian families CAS1 and CAS2, of the major
      genetic group (MGG) 1, 29% to MGG 2 and 3 families (spacers 33-36 missing) and
      17% to the ancestral East African Indian (EAI) family. Finally, nearly 10% of the
      isolates belonged to the W-Beijing family in a broad sense, also in the MGG 1
      group. In conclusion, historic clones of the MGG 1 group of M. tuberculosis are
      responsible for roughly 60% of all tuberculosis cases in Mumbai. Together with
      the fact that organisms presumably of European descent (such as the Haarlem
      family) were only rarely found, our observations suggest that tuberculosis in
      Mumbai, India is essentially caused by historical clones of tubercle bacilli
      undergoing active circulation due to uncontrolled demography, high prevalence of
      the disease, and a paucity of resources.

PMID- 15862460
TI  - Molecular characterization of a new serovar of Salmonella bongori 13,22:z39:-
      isolated from a lizard.
AB  - Three Salmonella strains isolated from a lizard (Gallotia simoni) in the "Isla
      del Hierro" (Canary Islands, Spain) were serotyped as Salmonella bongori serotype
      13,22:z39:-, which has not been described in the Kauffmann-White scheme of
      Salmonella serovars. In order to shed light on the assignment of those strains to
      the S. bongori species, several genes were amplified and/or sequenced. The iroB
      gene has been reported to be present only in S. enterica, while the invA gene has
      been described as being a helpful tool in distinguishing Salmonella from other
      bacterial species. Both genes were amplified and, as expected, only invA could be
      amplified. The fliC gene, encoding the phase 1 flagellin fljB gene, encoding
      phase 2 flagellin, and the gapA gene, which is believed to present polymorphic
      alleles among different subspecies, were amplified and sequenced. The sequence
      obtained from fliC(z39) matched with the sequences fliC(z39) obtained from other
      serovars. The sequence obtained from gapA clustered into the S. bongori group
      when it was compared to others previously described. We conclude that these three
      isolates are members of the S. bongori species representing a new serovar that
      will be described in the next supplement to the Kauffmann-White scheme.

PMID- 15862461
TI  - Molecular identification of the first human isolate belonging to the Veillonella
      ratti-Veillonella criceti group based on 16S rDNA and dnaK gene sequencing.
AB  - Anaerobic gram-negative cocci belonging to the genus Veillonella are currently
      subdivided into eight species. Among them, four have been isolated either from
      human flora or from clinical samples during infectious processes: Veillonella
      atypica, V. dispar, V. parvula and V. montpellierensis. To date, the four other
      species have only been found in animals. In particular, V. ratti and V. criceti,
      since their characterization, have been exclusively reported from mouth and
      intestine of rodents. We report here for the first time a human isolate belonging
      to the V. ratti-V. criceti group recovered in mixed aerobic-anaerobic flora from
      a semen sample in a 24-year-old man attending the urology unit of our hospital
      for infertility. Identification of the isolate was based on 16S ribosomal DNA and
      dnaK gene sequencing. Since then, two strains of Veillonella sp. recovered from
      semen samples remained unidentified to the species level, and 16S rDNA-based
      phylogenetic analysis revealed that they might represent novel taxa within the
      genus Veillonella. Taken together, these observations suggest that host
      restriction may not exist in the genus Veillonella and that bacterial diversity
      remains underestimated both within this genus and in human semen.

PMID- 15862463
TI  - The use of Chinese hamster ovary (CHO) cells in the study of ion channels.
AB  - The line of epithelial-like Chinese hamster ovary (CHO) cells was initiated by
      T.T. Puck in 1957. Since then, CHO cells have become a widely used mammalian
      expression system in industry and science. This paper discusses the different
      features of CHO cell physiology as well as the specific aspects of using these
      cells for ion channel studies; among the discussed features are the culturing and
      transfection of CHO cells, details of electrophysiological recordings from them
      and applications for the study of ion channel physiology and pharmacology.
      Examples of successful reconstitution of mammalian ion channels in CHO cells
      discussed in the paper include reconstitution of KCNQ channel regulation by
      muscarinic acetylcholine receptors and the study of the amiloride-sensitivity of
      epithelial sodium channels (ENaC).

PMID- 15862464
TI  - HEK293 cell line: a vehicle for the expression of recombinant proteins.
AB  - The HEK cell line has been extensively used as an expression tool for recombinant
      proteins since it was generated over 25 years ago. Although of epithelial origin,
      its biochemical machinery is capable of carrying out most of the post
      translational folding and processing required to generate functional, mature
      protein from a wide spectrum of both mammalian and non-mammalian nucleic acids.
      Though popular as a transient expression system, this cell type has also seen
      wide use in stably transfected forms (i.e. transformed cells) to study a variety
      of cell-biological questions in neurobiology. The principal attributes which have
      made the HEK cell a popular choice among electrophysiologists to study isolated
      receptor channels include; its quick and easy reproduction and maintenance;
      amenability to transfection using a wide variety of methods; high efficiency of
      transfection and protein production; faithful translation and processing of
      proteins; and small cell size with minimal processes appropriate for voltage
      clamp experimentation. These, and other attributes, also mean that complementary
      biochemical/cell biological evaluations of expressed proteins can be performed in
      concert with functional analyses to establish detailed pharmacological and
      biophysical profiles for the action of new drugs and their targets. The increased
      amount of sequence information available from the human genome has placed greater
      emphasis upon heterologous cell expression systems as targets for high throughput
      structure-function evaluation of novel drug targets and disease markers. Here we
      have highlighted some of the innate characteristics of the HEK cell in order that
      its suitability as a vehicle for the expression of a gene product can be assessed
      for particular needs. We have also detailed some of the standard methods used for
      transfection and obtaining functional data from electrophysiological recording
      techniques.

PMID- 15862465
TI  - Dorsal root ganglion neurones in culture: a model system for identifying novel
      analgesic targets?
AB  - Ion channels represent attractive targets in the development of novel analgesics
      for the treatment of pain. Dorsal root ganglion (DRG) neurones in culture can
      share characteristics with nociceptors in vivo and are frequently used to
      investigate the ion channels that underlie the transduction of noxious stimuli
      into electrical activity during sensory processing. In this article, I describe
      the methods used to prepare cultures of DRG neurones including the procedures for
      the dissection, enzymatic dissociation and plating. The criteria used to identify
      putative nociceptors in vitro are reviewed and using the M-current as an example
      I highlight how potential analgesic targets can be identified by combining the
      use of the voltage clamp technique with the use of selective pharmacological
      agents.

PMID- 15862466
TI  - The rat retinal ganglion cell in culture: an accessible CNS neurone.
AB  - Retinal ganglion cells are vital for vision, some have intrinsic light sensing
      properties and in retinal networks display complex computational abilities.
      Furthermore they are implicated in a very common form of blindness, glaucoma as
      well some the symptoms of AIDS. Retinal ganglion cells, unlike many neurones of
      the central nervous system, have a clearly defined physiological role and can be
      identified in primary cultures with ease. Here we detail the cell culture and
      electrophysiological methods required to obtain recordings on the voltage-gated
      and ligand-gated ion currents and channels expressed by these neurones.
      Information is given on the range of non-ionotropic receptors that are thought to
      be present on these cells and what role they may have as model systems in the
      pharmacological and pharmaceutical research environment.

PMID- 15862467
TI  - The optic nerve: a model for axon-glial interactions.
AB  - The rodent optic nerve is a model tissue for the physiological investigation of
      axonal-glial interactions in a typical CNS white matter tract. There is strong
      evidence that nerve transmission is maintained by a considerable degree of
      dynamic signalling between axons and glia through a variety of mechanisms, such
      as regulation of the ionic environment, energy metabolism and calcium signalling.
      This review focuses on the methods used to examine axonal and glial functions and
      interactions, primarily in the rodent optic nerve. Techniques encompass
      intracellular microelectrodes, sucrose- and grease-gap recordings of membrane
      potentials, suction electrode to measure compound action potentials, the use of
      ion-sensitive electrodes, patch clamping and imaging. An overview of the
      advantages and drawbacks of each technique is given and the application of each
      to the understanding glial and axonal physiology is briefly discussed.

PMID- 15862468
TI  - The use of the rat isolated vagus nerve for functional measurements of the effect
      of drugs in vitro.
AB  - In this article we describe how to dissect, set up and use the rat isolated vagus
      nerve in a 'grease gap' apparatus which provides a simple and practical method
      for measuring the effects of drugs on the membrane potential of axons in the
      nerve in vitro. Some discussion of the origins and development of the technique
      as well as the strengths and disadvantages of the preparation as a
      neuropharmacological tool are included. The vagus nerve conducts action
      potentials in at least three distinct types of axons that can be measured
      extracellularly as compound action potentials and distinguished on the basis of
      their conduction velocity and excitability. Activity in myelinated A fibres and
      unmyelinated C fibres can be measured separately easily. The axons express
      receptors for a wide range of putative neurotransmitter agents including 5-HT,
      GABA and ATP as well as other agents such as capsaicin, anandamide, bradykinin
      and prostanoids. Responses to all of these chemicals can be measured as a
      depolarization of the nerve fibres. The vagus nerve is an important target for a
      wide range of drugs and the isolated preparation provides a fairly simple
      preparation for studying their effects. The isolated vagus nerve is also a
      convenient system in which the effects of drugs that have been discovered using
      heterologous expression systems can be assayed on receptors and ion channels that
      are expressed in a native neural system.

PMID- 15862469
TI  - The rat spinal cord slice: Its use in generating pharmacological evidence for
      cholinergic transmission using the alpha7 subtype of nicotinic receptors in the
      central autonomic nucleus.
AB  - Lamina X surrounds the central canal of the spinal cord and is an important site
      for the convergence of somatic and visceral afferent inputs relaying nociceptive
      information. Lamina X contains sympathetic preganglionic neurons (SPN) in the so
      called central autonomic nucleus which may participate to viscero-autonomic
      reflexes. Here, we describe a transversal slice preparation of postnatal rat
      thoracolumbar spinal cord which allows the detailed characterization of the
      morphology, electrophysiological properties, synaptic activities and receptor
      pharmacology of neurons surrounding the central canal. By means of the patch
      clamp technique, in its whole cell configuration, and by the use of various
      pharmacological tools, we show here that lamina X neurons of the central
      autonomic nucleus express functional alpha7 nicotinic receptors which are located
      postsynaptically on SPNs where they are involved in a fast cholinergic
      transmission. Thus, this in vitro preparation is useful to study the mechanisms
      and the pharmacology of viscero-autonomic reflexes.

PMID- 15862470
TI  - The use of small interfering RNA to elucidate the activity and function of ion
      channel genes in an intact tissue.
AB  - Small interfering RNA (siRNA) directs the targeted destruction of mRNA encoding a
      specific protein, in a process known as RNA interference (RNAi). This stops
      translation of the targeted mRNA into protein, effectively silencing the gene.
      RNAi is a recent discovery, identified in mammalian cells in 2001, but it has
      rapidly advanced into a practical technique and is being used increasingly to
      investigate mammalian gene function. Tools are available to induce RNAi in cell
      lines, intact tissue preparations and even in vivo. Depending on the method used,
      loss of gene expression may be transient or sustained, enabling a wide range of
      functions to be investigated. RNAi therefore offers a powerful technique that can
      be used to produce targeted knockout of ion channel genes in mammalian cells. Its
      applications potentially include identification of ion channel function in health
      and disease, identification of novel channel genes and drug target validation.
      This paper outlines our current understanding of siRNA and the experimental
      requirements for producing efficient RNAi and gene silencing. Effective RNAi
      requires an appropriate siRNA sequence to be designed and an efficient method for
      delivering the siRNA to the cells of interest. Since not all potential siRNA
      sequences are effective, it is also important to verify the loss of gene
      expression by measuring the level of channel protein remaining. Limitations of
      the methods available for delivering siRNA are one of the main obstacles to
      producing efficient RNAi, especially in intact tissue preparations. Here we
      describe an in vitro method for targeted RNAi against the TASK-1 potassium
      channel gene in an isolated vascular preparation, using a DNA construct to direct
      the expression of siRNA, along with a non-viral method for transfecting cells
      within the vessel. Successful silencing of the TASK-1 gene is verified by
      immunostaining with an antibody directed against the TASK-1 protein.

PMID- 15862471
TI  - COMT (Val158Met) polymorphism is not associated to neuropathic pain in a Spanish
      population.
AB  - It is well known that the response to painful stimuli varies between individuals
      and this could be consequence of individual differences to pain sensitivity that
      may be related to genetic factors. Catechol-O-methyltransferase (COMT) is one of
      the enzymes that metabolize catecholamine neurotransmitters. Differences in the
      activity of COMT influence the functions of these neurotransmitters. A single
      nucleotide polymorphism (Val158Met) of COMT leads to a three to four fold
      reduction in the activity of the enzyme and has been associated to modifications
      in the response to a pain stressor. Neuropathic pain is a progressive nervous
      system disease due to an alteration of the peripheral or central nervous system.
      To elucidate the possible role of COMT polymorphism in the susceptibility to
      neuropathic pain, we have performed a case-control study in a Spanish population.
      Analysis of the (Val158Met) COMT polymorphism was performed by PCR amplification
      and DNA digestion with restriction enzymes. Our study concludes that functional
      Val158Met polymorphism of COMT gene is not associated to increased susceptibility
      to neuropathic pain.

PMID- 15862472
TI  - GABAB receptors on central terminals of C-afferents mediate intersegmental Adelta
      afferent evoked hypoalgesia.
AB  - The current study tested the hypothesis that repetitive activation of sciatic
      Adelta-afferents evokes a saphenous C-afferent hypoalgesia mediated by pre
      synaptic GABA(B) receptors. Tonic activation of sciatic Adelta-afferents was
      produced by cutaneous application of dimethyl sulfoxide (DMSO) followed by
      repetitive thermal activation of Adelta-afferents on the dorsolateral hind paw.
      The tonic activation of sciatic Adelta-afferents produced hypoalgesia in
      saphenous C-afferents. Intrathecal administration of the GABA(B) receptor
      antagonist, saclofen, attenuated saphenous hypoalgesia demonstrating at least
      partial mediation by central GABA(B) receptors. To determine if this central
      GABA(B) receptor activation occurs at pre-synaptic primary afferent terminals or
      postsynaptic spinal cord neurons, the dorsal hind paws of mice were infected with
      a recombinant herpes simplex virus type 1 (HSV-1) designed to selectively knock
      down expression of the GABA(B1a) receptor subunit (PAGB1a) in primary afferents
      or a control virus encoding the E. coli lacZ gene (PZ). Four weeks after
      infection, GABA(B) receptor immunoreactivity in the superficial dorsal horns
      ipsilateral to PAGB1a application was reduced and hypoalgesia in saphenous C
      afferents was attenuated when compared to PZ-infected mice. These findings
      indicate an intersegmental, sciatic Adelta-afferent-evoked hypoalgesic effect on
      saphenous C-afferent responses that is mediated by pre-synaptic GABA(B) receptors
      on the terminals of those C-afferents.

PMID- 15862473
TI  - Psychosocial behaviour and health care utilization in patients suffering from
      temporomandibular disorders diagnosed on the basis of clinical findings and MRI
      examination.
AB  - The aim of this study was to evaluate psychosocial behaviour and differences in
      health care utilization between subgroups of patients suffering from
      temporomandibular disorders, using both clinical examination and magnetic
      resonance imaging (MRI). MATERIALS AND METHODS: 70 patients were examined
      according to the research diagnostic criteria for temporomandibular disorders
      (RDC/TMD), and were divided into groups according to their clinical diagnoses.
      MRIs were acquired and joint-related RDC/TMD diagnoses were modified on the basis
      of MRI findings. Group I suffered from joint pathology, group II from myofascial
      pain and group III from a combination. Non-parametric statistics were used to
      reveal group-related differences in psychosocial and behavioural aspects.
      Differences in group assignment based on clinical and MRI examination were
      assessed (kappa statistics). RESULTS: MRI findings led to group assignments that
      were different from clinical assignments (k = 0.3). For both types of assignment,
      patients with myofascial pain displayed higher somatization scores, used more
      splints and consulted more physicians. For clinical assignment only, depression
      scores were higher in the myofascial pain group. For MRI based assignment, sex
      differences were significant between groups I and III. CONCLUSION: Somatization
      specific behaviour is more widespread in patients suffering from exclusively
      myofascial pain than in patients presenting joint pathology. Inconsistencies in
      differences of other psychosocial variables between groups of TMD patients seem
      to be related to differences in group assignment either with or without objective
      information on joint pathology.

PMID- 15862474
TI  - Effects of pulsed versus conventional radiofrequency current on rabbit dorsal
      root ganglion morphology.
AB  - Lesioning using radiofrequency (RF) current has been increasingly used in
      clinical practice for the treatment of pain syndromes. Although formation of heat
      causing "thermocoagulation" of the nervous tissues is thought to be responsible
      of the clinical outcome, a more recent modality of RF application named pulsed
      radiofrequency (PRF) delivers the RF current without producing destructive levels
      of heat. In our study, we compared the effects of conventional RF (CRF) and PRF
      on rabbit dorsal root ganglion (DRG) morphology, including also control and sham
      operated groups. The setting of the experiment and the RF parameters used were
      similar to those used in current clinical practice. The specimens were analyzed
      both with light microscopy and electron microscopy, two weeks after the
      procedure. At the light microscopic level, all groups had preserved the normal
      DRG morphology and no differences were observed between them. In the electron
      microscopic analysis there were no pathological findings in the control and sham
      operated groups. But the ganglion cells in the RF groups had enlarged endoplasmic
      reticulum cisterns and increased number of cytoplasmic vacuoles which were more
      evident in the CRF group. Some of the ganglion cells in the CRF group had
      mitochondrial degeneration, nuclear membrane disorders or loss of nuclear
      membrane and neurolemma integrity. The myelinated and unmyelinated nerve fibers
      were of normal morphology in all groups. Our results suggest that PRF application
      is less destructive of cellular morphology than CRF at clinically used "doses".
      Before making certain judgements, more experimental and clinical studies should
      be planned.

PMID- 15862475
TI  - The causal status of pain catastrophizing: an experimental test with healthy
      participants.
AB  - In the current study we report findings on the effects of experimentally induced
      catastrophizing about pain on expected pain, experienced pain and
      escape/avoidance behavior during a cold pressor task in a sample of healthy
      participants. It was hypothesized that increasing the level of catastrophizing
      would result in a higher level of expected pain, a higher level of experienced
      pain, and a shorter duration of ice-water immersion. Also, it was hypothesized
      that these relations might be stronger for participants who already
      catastrophized about pain prior to the experiment. The results demonstrated that
      despite the successful attempt to induce catastrophizing, this neither
      significantly affected expected pain, experienced pain, and duration of ice-water
      immersion, nor were these relations moderated by the pre-experimental level of
      catastrophizing. Although the level of catastrophizing was successfully
      manipulated, more similar experiments are necessary in order to give a more
      definite answer on the possible causal status of pain catastrophizing.

PMID- 15862476
TI  - Health related quality of life and quantitative pain measurement in females with
      chronic non-malignant pain.
AB  - The aim of the present study was to assess, compare, and correlate the pain
      response to an experimental pain stimulus (hyperalgesia to pressure pain
      threshold (PPT) measured from different body sites), the pain intensity (VAS) of
      the habitual pain, and quality of life parameters (SF-36) in groups of females
      with chronic non-malignant pain syndromes. Forty female pain patients with
      fibromyalgia/whiplash (n = 10), endometriosis (n = 10), low back pain (n = 10),
      or rheumatoid arthritis (n = 10), as well as 41 age-matched healthy female
      controls participated in the study. The fibromyalgia/whiplash patients scored
      significantly higher (p < 0.04) VAS ratings (median rating = 7.0) than the
      endometriosis (6.0), low back pain (6.0), and rheumatoid arthritis (3.5)
      patients. All fours patient groups had significantly lower PPTs at all sites as
      compared with controls. The fibromyalgia/whiplash patients experienced the
      highest influence of pain on their overall health status, particularly vitality,
      social function, emotional problems, and mental health. A significant negative
      correlation was found between VAS rating and quality of life (p < 0.04).
      Significant correlation (p < 0.05) was found between pressure hyperalgesia
      measured at lowest PPT sites and the impairment of SF-36 physical function as
      well as mental health parameters. This study demonstrates significant generalised
      pressure hyperalgesia in four groups of chronic pain patients, correlations
      between degree of pressure hyperalgesia and impairment of some quality of life
      parameters, and increased pain intensity of the ongoing pain is associated with
      decreased quality of life.

PMID- 15862477
TI  - Memories of parental rearing and perceived self-image in groups of chronic pain
      patients.
AB  - OBJECTIVES: The aim of this study was to analyze the relationships between
      perceived parental rearing styles as determining factors of self-image in chronic
      pain patients, and to test the hypothesis of two different groups inherent to the
      pain sample. METHODS: In this study, 152 patients with chronic pain participated.
      The sample was divided into two groups by means of hierarchical cluster analysis
      on the Minnesota multiphasic personality inventory, version 2. Cluster 1
      comprised 116 individuals (44 men and 72 women) with a "conversion V" MMPI-2
      profile, and cluster 2 comprised 21 individuals (5 men and 16 women) with a
      "general elevated" MMPI-2 profile. The patients were investigated by means of the
      structural analysis of social behavior (SASB), the Giessen test (GT), the locus
      of control scale (LOC) and the EMBU questionnaire (My memories of parental
      upbringing). RESULTS: The results show significant associations between memories
      of parental rearing and self-image as adults and are in line with results from
      previous studies describing two psychologically different groups inherent to
      chronic pain patients. CONCLUSIONS: The significant differences between healthy
      controls, pain patients and between clusters of pain patients on parental rearing
      scales, and the significant relationship between memories of parental rearing and
      self-image provide therapists with a special approach to the treatment of chronic
      pain patients in accordance to social cognitive theories and the psychodynamic
      theoretical construct of introjection as an early process in the development of
      self-images.

PMID- 15862478
TI  - Psychiatric comorbidity in medication overuse headache patients with pre-existing
      headache type of episodic tension-type headache.
AB  - BACKGROUND: Medication overuse headache (MOH) mostly evolves from migraine and
      episodic tension-type headache (ETTH). Chronic tension-type headache (CTTH) is
      another headache type that evolves over time from ETTH. It is well known that
      psychiatric comorbidity is high in MOH patients. AIM: To investigate the
      frequency of psychiatric comorbidity, and the intensity of depression and anxiety
      in MOH patients evolving from ETTH and to compare results with CTTH patients and
      MOH patients evolving from migraine. METHODS: Twenty-eight CTTH (Group C) and 89
      MOH patients were included into the study. MOH patients were divided into two
      groups according to their pre-existing headache types: MOH patients with pre
      existing ETTH (Group E, n = 31), and with pre-existing migraine (Group M, n =
      58). All patients were interviewed with a psychiatrist and SCID-CV and SCID-II
      were applied. Beck Anxiety Inventory and Beck Depression Inventory scales were
      also performed. RESULTS: Eleven patients (39.3%) in Group C, 21 patients (67.7%)
      in Group E, and 31 patients (53.7%) in Group M were diagnosed to have comorbid
      psychiatric disorders. The psychiatric comorbidity was found significantly higher
      in Group E than Group C. In Group E, mood disorders were found significantly
      higher, but the difference between the two groups with regard to anxiety
      disorders was insignificant. Mean depression scores were significantly higher in
      Group E than Group C. The mostly diagnosed type was obsessive-compulsive
      personality disorder in all the three groups, and was statistically significant
      in Group M than Group C. CONCLUSION: Psychiatric comorbidity in MOH patients with
      pre-existing ETTH is common as in those with pre-existing migraine headache and
      MOH with regard to developing psychiatric disorders should be interpreted as a
      risk factor in chronic daily headache patients.

PMID- 15862479
TI  - Altered processing of pain-related information in patients with fibromyalgia.
AB  - Pressure pain thresholds (PPTs) and event-related potentials (ERPs) elicited by
      emotional words were analyzed in 12 patients with fibromyalgia (FM) and 12
      matched healthy subjects. PPTs were assessed at the middle finger of both hands,
      before and after the experiment. Overall, FM patients and healthy subjects did
      not differ in PPT. Nevertheless, FM patients as compared with healthy controls
      were characterized by a significant enhancement of pain sensitivity from the
      beginning to the end of the experiment indicating a long lasting sensitization
      due to repeated stimulation. ERPs were recorded during a language decision task
      where subjects had to react to unpleasant pain-related and emotionally neutral
      words depending on syntactic or orthographic cues. An emotional category effect
      was observed on N400 and P300 components of the ERP, indicating that unpleasant
      words elicited more positive amplitudes than neutral words. A significant group
      effect was observed on P200 amplitudes, showing reduced amplitudes in FM patients
      as compared to healthy controls. Furthermore, unpleasant pain-related compared to
      neutral words triggered significantly enhanced late positive slow waves in
      healthy controls, while a comparable effect was not found in FM patients. The ERP
      and PPT data suggest that FM patients are characterized by an altered cognitive
      processing of pain-related information and by an abnormal adaptation to
      mechanical pain stimuli, respectively.

PMID- 15862480
TI  - Health related quality of life of patients with refractory angina before and one
      year after enrolment onto a refractory angina program.
AB  - OBJECTIVE: This study was designed to assess the impact of a refractory angina
      programme on the health related quality of life for patients with chronic
      refractory angina (CRA) one year following enrolment. DESIGN: A one year
      prospective audit. SETTING: Specialist refractory angina clinic at a tertiary
      cardiac referral centre. PATIENTS: 69 consecutive refractory angina patients
      referred to a regional refractory angina centre from 1/03/2001 to 1/09/2002.
      INTERVENTIONS: Pain treatment algorithm in accordance with the recommendations of
      the national refractory angina guideline committee. MAIN OUTCOME MEASURES:
      Improvements in quality of life indices were assessed using Seattle angina
      questionnaire (SAQ), and short form-12 (SF-12) with changes in mood determined
      using the hospital anxiety and depression (HAD) questionnaire. RESULTS: All
      dimensions of the SF-12 and SAQ were superior at one year with significant
      improvement seen with the mental component of SF-12 (p = 0.023), and four of the
      five SAQ domains, angina stability (p = 0.028), angina frequency (p=0.02),
      treatment satisfaction (p=0.001) and quality of life (p < 0.001). All the
      significant changes within the SAQ domains were large enough to be considered
      clinically relevant. At one year the anxiety and depression domains were
      significantly improved from baseline (p = 0.015, 0.018) with clinical anxiety
      levels falling significantly from 55% to 40%, a relative reduction of 28% (p =
      0.008). CONCLUSIONS: Implementation of the national refractory angina guidelines
      in a prospective study of 69 consecutive CRA patients significantly improved
      health related quality of life status at one year.

PMID- 15862481
TI  - A prospective study of the relationship between musculoskeletal or psychological
      complaints and muscular responses to standardized cognitive and motor tasks in a
      working population.
AB  - The present study sought to determine the relationship between musculoskeletal or
      psychological complaints and muscular responses to standardized cognitive and
      motor tasks. The prospective study design examined (i) whether complaint severity
      predicts muscular responses during standardized tasks and (ii) whether the
      muscular responses predict changes in complaint severity over one year.
      Musculoskeletal and psychological complaints were recorded by monthly reports the
      four months preceding and 12 months succeeding a work session in the laboratory;
      complaint-severity indices were computed from complaint-severity scores
      (intensity scorexduration score). Surface electromyography (EMG) was recorded
      bilaterally from the upper trapezius, middle deltoid, and forearm extensor
      muscles in 45 post-office workers (30 women) during two identical task series.
      Between the series, exhausting submaximal muscle contractions (25% of peak
      torque) were performed. In adjusted regression models, no relations between
      musculoskeletal complaints the last four months and muscle activity during the
      task series were found. However, psychological complaints the last four months
      predicted higher muscle activity levels and a steeper rise in muscle activity in
      the muscles not engaged in motor task performance. Sleep disturbance was the
      strongest individual predictor of increased muscle responses. In contrast,
      psychological complaints the last four months predicted lower EMG levels in the
      task-engaged muscle during the complex-choice-reaction-time tasks. None of the
      muscle-activity responses to the standardized tasks predicted changes in severity
      of musculoskeletal or psychological complaints over the subsequent one-year
      period. In conclusion, psychological complaints predict different responses in
      task-engaged and non-involved muscles during cognitive and motor tasks.
      Musculoskeletal complaints did not predict responses to the tasks.

PMID- 15862482
TI  - Differences in unpleasantness induced by experimental pressure pain between
      patients with fibromyalgia and healthy controls.
AB  - Pain possesses both sensory and affective dimensions, which are highly correlated
      yet distinct. Comparison of these dimensions within experimental pain settings
      has resulted in the construct of relative unpleasantness. Relative unpleasantness
      is defined as the amount of affective unpleasantness elicited for a given sensory
      magnitude. The aim of this study was to determine the relationship between
      affective and sensory components of evoked pain in subjects with fibromyalgia
      (FM) and healthy controls. Here we show that patients with FM unexpectedly
      display less relative unpleasantness than healthy controls in response to random
      noxious pressure stimuli. Relative unpleasantness was not correlated with
      distress, anxiety, or depression, which were pronounced in the FM group. Clinical
      pain in patients with FM was perceived to be more unpleasant than the evoked pain
      stimuli. These results are consistent with the concept that chronic pain may
      reduce the relative unpleasantness of evoked pain sensations.

PMID- 15862483
TI  - No release of interstitial glutamate in experimental human model of muscle pain.
AB  - Glutamate may be released from muscle nociceptors and thereby contribute to
      mechanisms underlying acute and chronic muscle pain. In vivo concentration of
      glutamate during muscle pain has not previously been studied in either animals or
      humans. In the present study, we aimed to study the in vivo concentration of
      glutamate before, during and after acute pain of trapezius muscle in humans using
      the microdialysis technique. In addition, we examined the nutritive skeletal
      muscle blood flow and the interstitial concentrations of lactate, glucose,
      glycerol, pyruvate and urea. Experimental pain and tenderness were induced by
      intramuscular infusion of a chemical mixture consisting of bradykinin,
      prostaglandin E(2), histamine and serotonin. One EMG-needle and one microdialysis
      catheter were inserted into non-dominant and dominant trapezius muscles on a
      standard anatomical point in 19 healthy subjects. Dialysates were collected at
      rest, during infusion and 60 and 120 min after stop of infusion. Local tenderness
      was recorded at baseline and at the end of experiment. Local pain was recorded
      during infusion. The infusion of chemical mixture was more painful than infusion
      of placebo (p < 0.05) and resulted in significantly higher local tenderness score
      than placebo (p = 0.007). There was no difference in change in interstitial
      concentrations of glutamate, lactate, glucose, glycerol, pyruvate and urea from
      baseline to infusion and post-infusion periods between chemical mixture and
      placebo (p > 0.05). Muscle blood flow increased significantly over time in
      response to infusion of chemical mixture and placebo (p = 0.001). However, we
      found no difference in changes in muscle blood flow between chemical mixture and
      placebo (p > 0.05). In conclusion, the present study demonstrates no signs of
      increased release of glutamate from myofascial nociceptors during and after acute
      experimentally induced muscle pain and tenderness.

PMID- 15862484
TI  - Long-term changes of c-Fos expression in the rat spinal cord following chronic
      constriction injury.
AB  - The expression of c-Fos protein has been used as a relative marker of nociceptive
      neuronal activity in the spinal cord following various noxious stimuli.
      Experiments were conducted to examine c-Fos expression in lumbar spinal cord (L3
      L6) following chronic constriction injury (CCI) in relation to nociceptive
      behavior over longer survival period up to 28 days. Development of mechanical
      allodynia was observed in the ipsilateral hind paw of CCI rats at day 3 and
      lasted up to 28 days. In contrast, the spinal c-Fos expression in CCI rats
      appeared in a biphasic manner. The highest number of c-Fos positive neurons
      occurred during the first week, followed by a decline at 7 and 14 days and
      reappearance at day 28 following injury. The early increase of c-Fos expression
      correlated with allodynia development, however, at longer survival period (28
      days) c-Fos positivity become comparable in both CCI and sham groups despite
      their obvious behavior differences. Our results suggest that, at least in the CCI
      model, the c-Fos protein expression should not be considered as a reliable index
      of pain sensation disorders.

PMID- 15862485
TI  - The long green line.

PMID- 15862486
TI  - Dr. Kenneth A.J. Mackenzie: truly he shone.

PMID- 15862487
TI  - Clinical utility and cost-effectiveness of routine preoperative computed
      tomography scanning in patients with colon cancer.
AB  - BACKGROUND: The aims of this study were to assess the clinical utility of the
      practice of routine preoperative CT scanning and to determine its cost
      effectiveness in colon cancer patients. METHODS: A 6-year database of colon
      cancer patients treated at a veterans affairs medical was reviewed to determine
      the influence of preoperative CT scanning on clinical management. Cost analysis
      involved comparison of the institutional cost of CT scanning with the cost
      savings provided by avoiding nontherapeutic operations. RESULTS: CT scans were
      obtained in 130 consecutive patients. CT scans provided information that was used
      in treatment planning in 43 (33%) patients and definitively altered the mode of
      treatment in 21 (16%) patients. The practice saved the institution $24,018 over 6
      years. CONCLUSION: Routine preoperative CT scanning definitively alters treatment
      in a small number of cases and is cost-effective.

PMID- 15862488
TI  - The effect of combat rations on bowel habits in a combat environment.
AB  - BACKGROUND: Combat rations have long been suspected to affect the bowel habits of
      deployed soldiers by causing significant constipation. This may create morbidity
      and result in decreased troop readiness. In a uniform population of deployed
      combat soldiers, we sought to determine the effect of combat rations on changes
      in bowel habits. METHODS: Over a 4-month period from December 2001 through March
      2002, 118 soldiers were followed prospectively using a bowel habit diary.
      Soldiers were evaluated by age, race, gender, past medical history, ration
      intake, and medications including fiber use. Subjects were then screened for
      changes in diarrhea and constipation. We performed an analysis to determine
      predictors for changing habits. RESULTS: There were 108 males and 10 females.
      Mean follow-up was 42.6 +/- 23.1 days. Groups were comparable in demographics,
      time in the combat zone, and fluid/fiber intake (P = not significant [NS]). No
      change in habits were found in 58%, 19% had an increase in constipation, 13% had
      an increase in diarrhea, and 10% had increase in both diarrhea and constipation,
      while 8% had improvements. CONCLUSION: Combat rations and environment have
      variable effects on bowel habits, with no loss in workdays. Although 64% of
      subjects experienced either no change or improvement, and 36% had worsened
      symptoms, this appears unrelated to ration or fiber intake.

PMID- 15862489
TI  - Examining the learning curve of laparoscopic fundoplications at an urban
      community hospital.
AB  - BACKGROUND: Laparoscopic fundoplication for gastroesophageal reflux disease is a
      procedure associated with specific complications, especially in a surgeon's early
      experience. The learning curve of this procedure was examined at a tertiary
      community institution. METHODS: A retrospective review of the first 100 cases
      performed at Royal Columbian Hospital was conducted. Two surgeons performed the
      majority of cases and routinely assisted each other. Patients were grouped
      chronologically with the first 50 cases defined as early institutional experience
      and a surgeon's first 20 cases defined as early personal experience. RESULTS:
      Operative time was longer in both the early institutional (117.8 versus 91.3
      minutes, P < .001) and personal experience (126.8 versus 89.7 minutes, P < .001).
      The rate of dysphagia requiring intervention was higher during the early
      institutional (22% versus 4%, P = .017) but not personal experience (19% versus
      8%, P = not significant). The conversion rate was 0%, reoperation rate was 1%,
      mean length of stay was 2.5 +/- 1.4 days, and the readmission rate was 5%; these
      outcomes were unaffected by the learning curve. CONCLUSIONS: There is a definable
      learning curve in laparoscopic fundoplication in terms of operative time.
      However, an acceleration of the personal learning curve in terms of dysphagia was
      observed with a two-surgeon collaborative approach. With careful patient
      selection conversion, reoperation, readmission, and complication rates equivalent
      to experienced centers can be achieved in the community setting early in the
      personal and institutional experience.

PMID- 15862490
TI  - Epidemiology, presentation, diagnosis, and outcomes of choledochal cysts in
      adults in an urban environment.
AB  - BACKGROUND: Choledochal cysts (CDC) are rare congenital cystic lesions of the
      biliary tract. In North America the incidence of CDC is estimated as 1/150,000;
      it is not clear that the disease pattern in North America is similar to that in
      Asia. METHODS: Retrospective chart review. Statistical analysis was under taken
      using Fisher's exact test. RESULTS: Presentation, epidemiology, diagnosis, and
      outcome were evaluated in 51 patients with CDC. Malignant transformation was
      identified in 4 patients presenting uniformly with jaundice (P = .027). Type 4a
      cysts (54.9%) were the most common cyst identified. Four (14%) type IVa and two
      (13%) type I cysts developed postoperative stricture. No patient developed
      cholangiocarcinoma after complete resection of their cyst. CONCLUSIONS: Types I
      and IVa cysts can be treated similarly with excellent outcome. However, our
      observation of a high proportion of type 4a cysts may represent a specific North
      American pattern of this disease requiring a re-evaluation of the classification
      system.

PMID- 15862491
TI  - Treatment of nonadhesive bowel obstruction following gastric bypass.
AB  - BACKGROUND: Bowel obstruction secondary to internal hernias following
      laparoscopic and open gastric bypass is well reported. The number of gastric
      bypasses being performed in the United States continues to increase. As many
      patients undergo surgery at centers geographically distant from their home,
      increasing numbers of patients will present to their local emergency rooms with
      abdominal complaints that will need to be addressed by general surgeons who are
      not performing bariatric surgery. METHODS: Review of a prospective database of
      patients operated on in a general surgery practice performing bariatric surgery.
      RESULTS: Over a 14-month period, 9 patients requiring operative intervention
      presented to our practice with nonadhesive bowel obstruction following both open
      and laparoscopic bariatric surgery. Causes of obstructions included cicatrical
      narrowing in the Roux limb at the transverse mesocolon defect (1 patient) and
      internal hernias through the transverse mesocolon (5 patients), Petersen's hernia
      (2 patients), and at the jejunojejunostomy (1 patient). Seven patients were
      treated laparoscopically and 2 underwent laparotomy. Our diagnostic and operative
      approach is described. CONCLUSIONS: Surgeons, including those not performing
      bariatric surgery, will be treating more patients with bowel obstruction
      following gastric bypass in the future. The etiology and management of bowel
      obstruction after gastric bypass differs from the conventional management of
      bowel obstruction. When surgery is required, most of these patients can be
      treated laparoscopically.

PMID- 15862492
TI  - Common channel length predicts outcomes of biliopancreatic diversion alone and
      with the duodenal switch surgery.
AB  - BACKGROUND: The optimal common channel (CC) length for malabsorptive weight loss
      surgeries is unknown even though these surgeries were developed in the 1970s
      (biliopancreatic diversion [BPD]) and the 1990s (biliopancreatic diversion with a
      duodenal switch [BPD DS]). We hypothesized that the length of the CC correlates
      with a successful weight loss result. METHODS: We evaluated 3 groups of patients
      based on the length of the CC whose duration of follow-up evaluation was at least
      1 year. We reviewed all patients who had either an open BPD (5 patients) or a BPD
      DS (119 patients) from August 1998 to October 2003, for which D.B.M. was the
      participating surgeon. RESULTS: Group I comprised 15 patients: their preoperative
      body mass index (BMI) was 53.9 kg/m(2); 73.3% of patients had a BMI more than 50,
      and the CC length was 150 cm. Group II comprised 76 patients: their preoperative
      BMI was 54.25 kg/m(2); 73.3% of patients had a BMI more than 50, and the CC
      length was 100 cm. Group III comprised 33 patients: their preoperative BMI was
      60.1 kg/m(2); 84% of patients had a BMI more than 50, and the CC length was 80 to
      90 cm. The mean weight loss in group I was 45 kg (44% mean excess weight loss).
      The mean weight loss in groups II and III was 55.8 and 61.5 kg, respectively (a
      57% and 54.8% mean excess weight loss, respectively) (all P < .05 by analysis of
      variance). A weight loss of greater than 50% of excess body weight occurred in
      40% of patients in group I versus 63% of patients in groups II and III combined
      (P < .01 by chi(2)). CONCLUSIONS: The length of the CC contributes significantly
      to successful excess weight loss in BPD and BPD DS patients. In general, the
      length of the CC should not exceed 100 cm.

PMID- 15862493
TI  - Factors related to the failure of radiographic recognition of occult
      posttraumatic pneumothoraces.
AB  - PURPOSE: Although posttraumatic pneumothoraces (PTXs) are common and potentially
      life threatening, the supine chest radiograph (CXR) is an insensitive test for
      their detection. Computed tomography (CT) often identifies occult pneumothoraces
      (OPTXs). Previous descriptions of OPTX topography have been poor. Our purpose was
      to define their distribution and aid in the targeting of thoracic ultrasound.
      METHODS: Posttraumatic supine CXRs and CTs were reviewed for occult, overt, and
      residual PTXs. PTXs were compared according to their apical, basal, anterior,
      lateral, medial, and posterior components. A comparative size index was
      calculated. RESULTS: Among 761 patients, 338 CT scans revealed 103 PTXs in 89
      patients; 55% were OPTXs. OPTXs were apical (57%), basal (41%), anterior (84%),
      lateral (24%), and medial (27%), with 0% posterior. CONCLUSIONS: CXR missed over
      half of all PTXs. OPTXs had a greater anterior versus lateral (nearly 4-fold) and
      both basal and apical versus lateral (2-fold) distribution. OPTXs are often
      located at easily accessible sonographic windows.

PMID- 15862494
TI  - The effect of obesity on bioimpedance cardiac index.
AB  - BACKGROUND: Cardiac performance may be assessed noninvasively at the patient's
      bedside by using thoracic bioimpedance. However, it is unclear if this technique
      can be used reliably in critically injured obese patients because of increased
      body habitus and chest wall mass. METHODS: A prospectively maintained database
      was used to identify all trauma patients admitted to the intensive care unit who
      underwent simultaneous measurement of cardiac performance by using both thoracic
      bioimpedance and thermodilution. Patients were divided into 2 groups based on
      their body mass index (BMI). Patients with a BMI less than 30 kg/m(2) were
      classified as nonobese, and patients with a BMI of 30 kg/m(2) or greater were
      categorized as obese. RESULTS: There were 285 patients who underwent 1,138
      simultaneous measurements of cardiac index by using both bioimpedance and
      thermodilution. There were 211 nonobese patients (BMI = 25 +/- 3 kg/m(2)) and 74
      obese patients (BMI = 34 +/- 4 kg/m(2)). Bioimpedance correlated well with
      thermodilution for the entire population (r = .84, P < .0001), and was reliable
      equally in obese (r = .85, P < .0001) and nonobese (r = .82, P < .0001) patients.
      There actually was less test bias in the obese group (-.06 +/- .69) than in the
      nonobese group (-.16 +/- .75, P = .04). CONCLUSIONS: Thoracic bioimpedance
      technology may be used reliably as a noninvasive alternative to pulmonary artery
      catheterization for assessment of cardiac performance in critically injured obese
      patients.

PMID- 15862495
TI  - Hepatitis C infection increases the risk of new-onset diabetes after
      transplantation in liver allograft recipients.
AB  - BACKGROUND: Recent evidence suggests that new-onset diabetes after transplant
      (NODAT) adversely affects orthotopic liver transplant (OLTX) patient and graft
      survival. The objective of this study is to evaluate the effect of hepatitis C
      infection on the natural history of NODAT. METHODS: A retrospective review of 492
      OLTX recipients at a single center was conducted from January 1993 to January
      2003. Patients were followed for a minimum of 12 months (range 12 months-10
      years). The study population consisted of 444 OLTX recipients who were either HCV
      positive (n = 206) or HCV negative (n = 238). NODAT was defined by the need for
      antidiabetic medication for at least 7 days starting anytime after OLTX.
      Statistical analysis was performed by using the Student t test, Kaplan-Meier
      survival, and chi-square tests. RESULTS: The overall incidence of NODAT was 33%
      (146/444). There was a significant difference in the development of NODAT between
      the HCV-positive group (82/206, 40%) and the HCV-negative group (64/238, 27%) (P
      < .001). Other independent risk factors for development of NODAT were male gender
      and age >50 years. CONCLUSION: Hepatitis C infection contributes to the
      development of diabetes mellitus in OLTX recipients. The mechanisms behind HCV
      infection and associated NODAT in HCV-positive OLTX recipients warrant further
      investigation.

PMID- 15862496
TI  - Use of a minimally invasive donor nephrectomy program to select technique for
      live donor nephrectomy.
AB  - BACKGROUND: Live donor nephrectomy (LDN) is a major surgical procedure with an
      accepted low mortality and morbidity. Minimally invasive donor nephrectomy (MIDN)
      has been shown to decrease the wound morbidity associated with the lumbotomy of
      the classic open technique. Transplant programs face the challenge of initiating
      their MIDN programs without jeopardizing the safety of the donor and the graft
      quality. We present the experience at the University of Calgary after the
      initiation of a MIDN program, with a preoperative selective approach using the 3
      major techniques for LDN. METHODS: From December 2001 to May 2004, 50
      consecutive, accepted, live kidney donors were evaluated and chosen to undergo
      nephrectomy by an open, laparoscopic, or hand-assisted technique. Patients were
      chosen for a particular technique based on the criteria of vascular anatomy, size
      of abdominal cavity, previous surgery, and technical implications for the
      recipient. RESULTS: A total of 15 open, 11 laparoscopic, and 24 hand-assisted
      nephrectomies were performed. There were no statistically significant differences
      in sex, age, or body mass index between the groups. There were statistically
      significant differences in surgical times (P < .001) and in the number of days
      spent in the hospital (P < .001). All kidneys had primary function. There were 2
      conversions in the hand-assisted group and 1 blood transfusion in the open group.
      Death-censored graft survival was 100% with an observation time of 20 months (SD
      +/- 9 months; range = 3-32 months). One graft from the hand-assisted group was
      lost from patient death with functioning graft 8 months after transplant.
      CONCLUSIONS: The learning curve for MIDN does not necessarily need to impact
      donor or recipient outcomes. The initiation of an MIDN program can be implemented
      safely if the cases are selected carefully and the use of the classic open
      technique is kept as an alternative.

PMID- 15862497
TI  - Supporting the Global War on Terror: a tale of two campaigns featuring the 250th
      Forward Surgical Team (Airborne).
AB  - BACKGROUND: Forward Surgical Teams (FSTs) are 20-person units designed to perform
      front-line, life-saving combat surgery. This study compares the employment,
      injuries encountered, and workload of an airborne FST in two widely varying
      campaigns. METHODS: The 250th FST provided far forward surgery for initial entry
      assaults and follow-on stability operations in Afghanistan (Operation Enduring
      Freedom [OEF]) and northern Iraq (Operation Iraqi Freedom [OIF]). Prospective
      data on all patients admitted to the 250th were analyzed. Data from civil affairs
      missions were evaluated retrospectively. RESULTS: In supporting combat
      operations, 127 surgical procedures (OEF: 68, OIF: 59) were performed on 98
      patients (OEF: 50, OIF: 48) during 17 months deployed (OEF: 6, OIF: 11). After
      initial assaults, stability actions varied significantly in terms of civil
      affairs missions (OEF: 3, OIF: 161). CONCLUSIONS: Although the number and types
      of combat casualties were similar between the campaigns, employment of the FST
      changed dramatically in OIF because of increased medical reconstruction missions.

PMID- 15862498
TI  - A population-based assessment of major trauma in a large Canadian region.
AB  - BACKGROUND: The cause of major trauma has not been well defined using population
      based methodologies. METHODS: We performed a population-based surveillance of
      major traumatic injuries in adult residents of the Calgary Health Region over a
      period of 3 years. RESULTS: A total of 1,475 victims of major trauma were
      identified (69.5 per 100,000/y). Males were at significantly higher risk as
      compared with females (104.5 vs. 35.2 per 100,000; relative risk = 3.0, 95%
      confidence interval = 2.64-3.35), as were urban as compared with rural residents
      (70.7 vs. 49.0 per 100,000; relative risk = 1.4; 95% confidence interval = 1.11
      1.91). A strikingly high incidence rate of major trauma was observed among those
      aged 85 years or more at 242.3 per 100,000 per year; elderly men were at 16.8
      fold (95% confidence interval = 11.04-24.79) higher risk than young females. The
      majority were unintentional (53.9 per 100,000/y). Suicide, assault, and homicide
      occurred at annualized rates of 8.5, 4.8, and 1.6 per 100,000, respectively.
      Motor vehicle-related injuries (39%), falls or jumps (33%), and being struck by
      an object or animal (10%) were responsible for the majority of traumas. Firearm
      injuries were relatively uncommon (2.0 per 100,000/y). The annual mortality rate
      was 20.0 per 100,000. CONCLUSIONS: This study provides rigorous, population-based
      data on the cause of severe injury in the Calgary Health Region. It is hoped that
      ongoing work in this area will be useful in the development of effective injury
      prevention and health resource allocation strategies.

PMID- 15862499
TI  - The impact of an interventional vascular specialty team on institutional
      endovascular aneurysm repair outcomes.
AB  - BACKGROUND: Endovascular aortic aneurysm repair (EVAR) is a technically
      demanding, resource-intensive procedure associated with a significant learning
      curve. In July 2002, the Department of Defense allocated nearly $5,000,000 for
      "Advances in Medical Practice" (AMP) and EVAR within the six major military
      medical centers in the United States Army. We sought to determine the impact of
      several institutional changes associated with the use of these funds. METHODS: We
      performed a single-institution, retrospective comparison of our early EVAR
      outcomes in physiologically similar patients before and after the use of AMP
      capital and the acquisition of a trained and equipped endovascular operative
      team. Morbidity, mortality, and operative variables were the main outcomes. Mean
      follow-up interval was 17.6 months. RESULTS: As of November 2004, a total of 114
      conventional open and endovascular AAA repairs were performed at our institution
      since our first EVAR in May 2000. Ten of 51 (20%) total AAA patients were treated
      with EVAR by a general vascular surgical team before the addition of an
      endovascular specialty team to the service in July 2002. An additional 28 of 63
      (44%) patients have been treated with EVAR since that time for a total of 38
      repairs. During the first year evaluated, 20% of aneurysms were repaired with
      EVAR versus 83% during the most recent year. Devices from four different
      manufacturers were used during the study interval. Patients treated by the
      endovascular team had significantly less mean estimated blood loss (EBL), packed
      red blood cells (PRBCs) transfused, intravenous (IV) contrast used, and shorter
      operative times. Morbidity, mortality, endoleaks, and other variables were
      similar. In linear regression analysis adjusting for complex, time-consuming
      repairs that required adjunctive procedures outside the realm of normal EVAR,
      endovascular team EVAR was independently associated with decreased mean operative
      time, EBL, PRBCs transfused, and IV contrast used. CONCLUSIONS: At a major
      military medical center, EVAR has become the preferred technique for the repair
      of abdominal aortic aneurysms. EVAR by a dedicated endovascular surgical team
      favorably impacts several important operative variables and may improve overall
      outcomes. Some of these operative variables may be device specific.

PMID- 15862500
TI  - Adrenal lesions assessed in the era of laparoscopic adrenalectomy: a modern day
      series.
AB  - BACKGROUND: To evaluate if laparoscopic adrenalectomy (LA) has changed the
      indications for adrenalectomy. METHODS: Retrospective analysis of patients with
      adrenal lesions referred from 1992 to 2004. Patients were divided into 2 groups,
      those before and those after the introduction of LA. RESULTS: One hundred eighty
      patients were assessed. Functioning lesions were found in 120 (66%) patients.
      Sixty patients had nonfunctioning tumors. Before the introduction of LA, 13% had
      primary hyperaldosteronism (PA), 23% had pheochromocytoma (Pheo), 20% had
      Cushing's syndrome (CS), and 7% had adrenal cortical cancer (ACC). No difference
      was seen in the percentage of patients referred after LA with Pheo (20%), CS
      (16%), or ACC (6%). There was, however, a significant increase in the percentage
      of patients referred with PA after introducing LA (13% vs. 27%), P < .05.
      CONCLUSION: Indications for adrenalectomy have not changed since introduction of
      LA. There was, however, an increased percentage of patients with PA referred
      since the introduction of LA.

PMID- 15862501
TI  - Detecting and defining hypothyroidism after hemithyroidectomy.
AB  - BACKGROUND: The incidence of hypothyroidism after hemithyroidectomy for benign
      thyroid disease remains uncertain. This study examines the incidence, natural
      history, and the factors contributing to hypothyroidism after hemithyroidectomy.
      METHODS: A retrospective review of patients undergoing hemithyroidectomy over 37
      months was performed. The incidence of postoperative hypothyroidism was based on
      thyrotropin values and clinical symptoms. The relationship between hypothyroidism
      and lymphocytic infiltration of the removed gland was investigated using stepwise
      logistic regression. RESULTS: Twelve of 66 patients (18%) became biochemically
      hypothyroid postoperatively. Four of the 12 patients (33%) subsequently became
      euthyroid without intervention. Of the remaining 8 patients, 4 (50%) had
      significant lymphocytic infiltration in the resected gland compared with 10 (19%)
      of the 54 euthyroid patients. Lymphocytic infiltration was associated with
      hypothyroidism but was age dependent. CONCLUSIONS: A minority of patients become
      hypothyroid after hemithyroidectomy. Some patients with biochemical
      hypothyroidism will become euthyroid without intervention. The impact of
      lymphocytic infiltrate on hypothyroidism after hemithyroidectomy is age
      dependent.

PMID- 15862502
TI  - Can cytology accurately predict benign follicular nodules?
AB  - BACKGROUND: The reliability of fine-needle aspiration (FNA) biopsy in
      differentiating benign from malignant follicular lesions of the thyroid has been
      the subject of renewed debate recently. Although surgical excision has been
      recommended for most follicular lesions identified by cytology, this approach may
      not be necessary in all cases. The goal of this study was to determine whether
      FNA could be used as a diagnostic tool to safely identify patients with
      follicular thyroid nodules who do not require immediate surgical intervention.
      METHODS: A retrospective review was performed on a sample of 24 patients
      diagnosed with either follicular adenoma or follicular carcinoma after surgical
      excision of a thyroid nodule. The initial FNA biopsies were independently
      reviewed by two experienced cytopathologists in a blinded fashion and
      subsequently compared with final histologic diagnoses. RESULTS: For pathologist
      A, overall accuracy was 58%. The positive predictive value (PPV) of a benign
      diagnosis was 82%; PPV of a malignant diagnosis was 38%. For pathologist B,
      overall accuracy was 63%. The PPV of a benign diagnosis was 83%; PPV of a
      malignant diagnosis was 42%. CONCLUSIONS: This study suggests that in follicular
      lesions of the thyroid, a benign FNA biopsy report from an experienced
      cytopathologist has a high positive predictive value. The predictive value may
      not, however, be high enough to preclude surgery; other factors may need to be
      considered before recommending a nonoperative approach.

PMID- 15862503
TI  - Selective unilateral parathyroid exploration: an effective treatment for primary
      hyperparathyroidism.
AB  - BACKGROUND: Unilateral neck exploration (UNE) is a well-recognized approach in
      the treatment of primary hyperparathyroidism (PHP). The objective of this study
      was to review the success of an approach involving UNE guided by preoperative
      sestamibi (SM) scanning. METHODS: All data were gathered by retrospective chart
      review. All patients undergoing surgery for the treatment of primary
      hyperparathyroidism at a tertiary referral center over a 3-year period were
      included in the study cohort. RESULTS: Fifty-two of 80 patients (65%) had an SM
      scan consistent with a solitary adenoma and were eligible for a UNE, with 57.5%
      (46/80) undergoing a UNE. Seventy-seven of 80 (96.3%) patients were normocalcemic
      after initial neck exploration. UNE was curative in 50 of 52 (96.2%) UNE eligible
      patients and required less operative time than bilateral neck exploration (mean,
      60 versus 87 minutes). CONCLUSION: Selective unilateral neck exploration, guided
      by preoperative SM scanning, is an effective surgical approach for the management
      of primary hyperparathyroidism.

PMID- 15862504
TI  - One-gland exploration for mediastinal parathyroid adenomas: cervical and
      thoracoscopic approaches.
AB  - BACKGROUND: In patients with sporadic primary hyperparathyroidism, preoperative
      localization studies may discover a solitary mediastinal parathyroid adenoma. In
      this circumstance a 1-gland mediastinal exploration, either cervical or
      thoracoscopic, may be curative. METHODS: In an 18-month period, 5 of 120
      consecutive patients underwent an initial 1-gland mediastinal exploration for a
      solitary mediastinal parathyroid adenoma and 2 patients had a 1-gland mediastinal
      exploration for persistent hyperparathyroidism. Clinical presentation, imaging
      studies, surgical techniques, and outcomes were reviewed. RESULTS: Sestamibi
      scans showed a mediastinal parathyroid adenoma in all 7 patients. Computed
      tomography provided anatomic localization of middle mediastinal parathyroid
      adenomas. A cervical approach was used in 4 patients who had a superior
      mediastinal parathyroid adenoma. Thoracoscopic excision was performed in 3
      patients with a middle mediastinal parathyroid adenoma. No complications
      occurred. Calcium and parathyroid hormone levels normalized in all patients.
      CONCLUSIONS: Sporadic primary hyperparathyroidism caused by a solitary
      mediastinal parathyroid adenoma can be treated successfully with 1-gland
      mediastinal exploration either by a cervical or a thoracoscopic approach as
      indicated by localization imaging.

PMID- 15862505
TI  - The association of cytokeratin-only-positive sentinel lymph nodes and subsequent
      metastases in breast cancer.
AB  - INTRODUCTION: The purpose of this study was to better characterize the clinical
      significance of cytokeratin immunohistochemistry (IHC)-only-positive lymph node
      metastases among patients with breast cancer. METHODS: We performed a
      retrospective review of 334 patients who underwent sentinel lymph node (SLN)
      biopsy from 1 February 1997 through 31 July 2001. SLN biopsies were evaluated
      using standard hematoxylin and eosin (H&E) techniques. If H&E was negative,
      cytokeratin IHC was performed. We then evaluated the incidence of subsequent
      regional and distant metastatic disease. RESULTS: Cytokeratin IHC was performed
      on 183 sentinel node biopsies from 180 patients comprising a total of 427
      sentinel lymph nodes. The procedures included lumpectomy and SLN biopsy (n = 83),
      mastectomy with SLN biopsy (n = 7), lumpectomy with SLN biopsy and completion
      axillary dissection (n = 80), and modified radical mastectomy with SLN biopsy and
      completion axillary dissection (n = 13). Cytokeratin IHC was negative in 175
      axillary specimens and positive in 8 (4.4%) from 8 different patients. In these
      eight specimens, deeper sections with subsequent H&E staining additionally
      identified micrometastasis in four patients. Three of these 8 patients (37.5%)
      developed distant metastatic disease compared with 1 of the 172 patients (0.6%)
      with negative cytokeratin IHC (P < .001). Additionally, one of the cytokeratin
      positive patients developed regional nodal metastasis compared with none of the
      172 cytokeratin-negative patients. CONCLUSIONS: Cytokeratin IHC provides a
      clinically relevant adjunct to H&E staining for evaluating sentinel lymph nodes
      in breast cancer. These data suggest that patients with cytokeratin-positive
      sentinel nodes are at increased risk for development of regional and distant
      metastatic disease.

PMID- 15862506
TI  - Risk counseling and management in patients with lobular carcinoma in situ.
AB  - BACKGROUND: The understanding of lobular carcinoma in situ (LCIS) has evolved
      since it was first described. LCIS once was thought to be a premalignant
      condition, but now it is considered a marker for increased risk for developing
      invasive breast cancer. We evaluated patient perception of risk, counseling, and
      subsequent management. METHODS: A community cancer registry of 3,605 cases of
      breast cancer was reviewed. Fifty-five (1.5%) patients with LCIS as their sole
      diagnosis were identified and these patients were sent a questionnaire. RESULTS:
      Forty of 55 patients completed the questionnaire for a 73% response rate. The
      patients' perception of lifetime risk for invasive cancer was variable. Surgeons
      performed the majority of counseling. Fourteen patients (35%) were placed on a
      selective estrogen-receptor modulator. Eleven patients (28%) had bilateral
      mastectomy. Three patients had unilateral mastectomy. Screening recommendations
      included an annual mammography (64%), a professional examination (64%), and a
      monthly self-breast examination (75%). CONCLUSION: A patient's perception of risk
      for invasive breast cancer after a diagnosis of LCIS is widely variable. Patients
      will adhere to suggested screening recommendations. Surgeons are performing the
      majority of counseling and must stay abreast on current recommendations.

PMID- 15862507
TI  - Geographic variation in sentinel node adaptation by practicing surgeons in
      Oregon.
AB  - BACKGROUND: The sentinel node biopsy (SNB) technique is an important tool in the
      diagnosis and treatment of breast cancer and melanoma. However, surgeons in
      Oregon have not universally adopted its use. METHODS: Mailed questionnaire.
      RESULTS: The response rate was 32%. Seventy-four (76%) of the surgical
      respondents perform routine SNB; 49% completed courses, and 32% learned the
      technique in residency. Sixty-one (89%) performed axillary dissection with their
      initial cases. It took 21 of 40 (52%) surgeons greater than a year to accrue 20
      cases. Of 23 surgeons (24%) not performing SNB, 89% believed it was an important
      skill to obtain, and 70% thought they would benefit from proctoring
      opportunities. Six (26%) did not have technological support at their hospital.
      Surgeons at hospitals with less than 50 beds (P = .001) and at rural hospitals (P
      = .003) were less likely to perform SNB. CONCLUSION: The majority of urban
      general surgeons in Oregon use SNB in their practice. However, the incorporation
      of SNB for surgeons practicing in smaller hospitals and rural settings is less
      frequent than in the urban environment. As SNB becomes the standard of care, we
      need to overcome these barriers so that patients can have access to this
      procedure in their own communities.

PMID- 15862508
TI  - Breast fine-needle aspirates with scant cellularity are clinically useful.
AB  - INTRODUCTION: Fine-needle aspirates (FNAs) with scant cellularity are considered
      inadequate by current cytopathology standards. We hypothesized that such
      aspirates are clinically useful. METHODS: A 10-year database of palpable breast
      lumps evaluated by FNA-based triple test (TT; FNA, breast imaging studies, and
      clinical breast examination) and triple test scores (TTSs; 3-9) was examined to
      identify FNAs with scant cellularity but without evidence of malignancy (negative
      SC-FNAs). These FNAs were correlated with the occurrence of any subsequent
      cancers (false-negative SC-FNAs) and with TTSs. RESULTS: Among a total of 324
      negative SC-FNAs, 9 cancers were subsequently found at sampled sites. Seven were
      associated with a suspicious or malignant TTS (scores of 5 or greater) and
      therefore still correctly diagnosed as malignant or suspicious for malignancy.
      The remaining two cancers were missed by both SC-FNA and TTS (false-negative rate
      for TTS of 0.6%); both had scores of 4 because of suspicious imaging.
      CONCLUSIONS: Scantly cellular but negative FNAs are useful (can avoid unnecessary
      invasive breast biopsy) in the evaluation of palpable breast masses, especially
      when interpreted in the context of the TT and TTS.

PMID- 15862509
TI  - Combination glutathione and anthocyanins as an alternative for skin care during
      external-beam radiation.
AB  - OBJECTIVE: Radiation dermatitis during therapy for breast malignancy can cause
      significant morbidity and delay treatment. RayGel (reduced glutathione and
      anthocyanins; Integrative Therapies, Portland, OR) appears to decrease this skin
      reaction, prompting us to undertake an objective evaluation of RayGel's
      effectiveness. METHODS: Patients undergoing whole breast external-beam
      irradiation were randomized to treatment with placebo or RayGel. Patients and
      investigators/staff were blinded to treatment assignment. Skin reaction was
      documented by photograph and severity scale. RESULTS: Thirty-two patients were
      enrolled. Thirty patients were randomized to receive placebo (n = 15) or RayGel
      (n = 15). Scores were calculated by percent of breast skin involved and grade of
      reaction. The group receiving RayGel had a lower average score, 93.7, versus the
      placebo group, 123.3. CONCLUSION: RayGel provides skin protection during
      radiation therapy, superior to that observed with standard skin care and placebo.
      This formula may reduce discomfort associated with breast irradiation and thereby
      allow more consistent completion of radiation courses for the treatment of breast
      cancer.

PMID- 15862510
TI  - Outcomes following resection of invasive and noninvasive intraductal papillary
      mucinous neoplasms of the pancreas.
AB  - BACKGROUND: Since any intraductal papillary mucinous neoplasm (IPMN) is at least
      premalignant, avoiding conversion to invasion by pancreatic resection should
      provide a survival advantage-but how much? METHODS: We reviewed 100 cases of IPMN
      that were resected. Survival was compared between 3 groups: noninvasive IPMN (n =
      75), invasive IPMN (n = 25), and invasive ductal adenocarcinoma (n = 24), the
      latter matched by tumor-node-metastasis (TNM) stage to the IPMN invasive group.
      RESULTS: The 5-year disease-specific survival was significantly better for the
      noninvasive IPMN group (100%) than the invasive IPMN group (46%). Tumor
      recurrence was infrequent with noninvasive IPMNs (1.3% benign IPMN). Recurrence
      was common in the invasive IPMN group (46%). Even the subgroup with stage 1
      disease had a 25% recurrence of malignancy. Survival curves were not different (P
      = .11) between the cases matched by stage for those with invasive IPMN cases
      versus cases with ductal adenocarcinoma. CONCLUSION: Patients with the invasive
      form of IPMN will have a similarly poor survival as those with ductal
      adenocarcinoma. In patients thought to have a benign IPMN, these lesions should
      be removed to avoid conversion to invasive cancer and to preserve the opportunity
      for the more favorable prognosis observed in this study.

PMID- 15862511
TI  - 1000 thyroidectomies in a tertiary care referral center.

PMID- 15862512
TI  - Capsaicin augments synaptic transmission in the rat medial preoptic nucleus.
AB  - The medial preoptic nucleus (MPN) is the major nucleus of the preoptic area
      (POA), a hypothalamic area involved in the regulation of body-temperature.
      Injection of capsaicin into this area causes hypothermia in vivo. Capsaicin also
      causes glutamate release from hypothalamic slices. However, no data are available
      on the effect of capsaicin on synaptic transmission within the MPN. Here, we have
      studied the effect of exogenously applied capsaicin on spontaneous synaptic
      activity in hypothalamic slices of the rat. Whole-cell patch-clamp recordings
      were made from visually identified neurons located in the MPN. In a subset of the
      studied neurons, capsaicin enhanced the frequency of spontaneous glutamatergic
      EPSCs. Remarkably, capsaicin also increased the frequency of GABAergic IPSCs, an
      effect that was sensitive to removal of extracellular calcium, but insensitive to
      tetrodotoxin. This suggests an action of capsaicin at presynaptic GABAergic
      terminals. In contrast to capsaicin, the TRPV4 agonist 4alpha-PDD did not affect
      GABAergic IPSCs. Our results show that capsaicin directly affects synaptic
      transmission in the MPN, likely through actions at presynaptic terminals as well
      as on projecting neurons. Our data add to the growing evidence that capsaicin
      receptors are not only expressed in primary afferent neurons, but also contribute
      to synaptic processing in some CNS regions.

PMID- 15862513
TI  - Auditory inhibitory gating in the amygdala: single-unit analysis in the behaving
      rat.
AB  - Inhibitory sensory gating has been proposed to be a fundamental physiological
      process that filters neural input. Its temporal properties could allow for a
      rapid influence on vigilance and attention processes. Inhibitory mechanisms are
      reflected by reductions in neural responsiveness to repeated and well-predicted
      stimuli; for auditory gating, this translates into an inhibition of the neural
      activation to subsequent tone stimuli embedded within sequential and identical
      tone presentations. Here we expand previous neurophysiological data on inhibitory
      gating by examining gating in the amygdala using single-unit recording in freely
      moving animals. Previous data have shown the amygdala to be important in
      mediating rapid auditory sensory processing involved in emotional conditioning.
      We measured inhibitory gating with two matching auditory tones presented in a
      repetitive fashion (10 ms tones, ISI = 500 ms and 10 s between pairs) for 1 h
      (360 pairs). The majority of the tone responsive units showed inhibitory gating
      (78/95 units) located in both the medial and lateral subnuclei of the amygdala.
      Different types of tone responses were gated, including both shorter- and longer
      duration excitatory tone responses as well as inhibitory tone responses.
      Different degrees of gating were found ranging from 100% inhibition (complete
      gating category) to 25% inhibition (graded gating category). The degree of gating
      varied over short-term and long-term time intervals. These findings demonstrate
      the existence of inhibitory gating in the amygdala and provide a detailed
      description of the basic properties of this rapid neural inhibition that could
      play an important role in filtering stimulus input.

PMID- 15862514
TI  - Effects of pinealectomy and the treatment with melatonin on the temporal lobe
      epilepsy in rats.
AB  - The aim of the present work was to analyze the effects of pinealectomy in the
      development of the epilepsy model induced by pilocarpine in adult male rats.
      Group I: Wistar male adult rats were submitted to pinealectomy, and 7 days after
      surgery, these animals received pilocarpine (350 mg/kg, i.p.) to induce three
      distinct behavioral phases: status epilepticus, seizure-free, and chronic phases.
      This late, as well as all control groups were continuously video-recorded for 60
      days, to study behavior parameters. These animals were killed and the brain
      sections were processed for Nissl and neo-Timm. Group II: Another group, also
      submitted to pinealectomy, received several injections of melatonin (2.5 mg/kg):
      20 min before, concomitantly with pilocarpine, 30 min, 1 h, and 2 h after
      pilocarpine administration. Some animals from group I and all from group II were
      sacrificed 48 h following status epilepticus onset to perform TUNEL assay. The
      latency for status epilepticus onset, status epilepticus length as well as
      mortality rate during status epilepticus were similar for pinealectomized and
      control groups. On the other hand, pinealectomized rats presented minor duration
      of the silent period, a higher number of spontaneous seizures during the chronic
      phase, increased number of TUNEL-positive cells (acute phase), increased neuronal
      loss, and marked supragranullar mossy fibers sprouting (chronic phase) in the
      hippocampal formation, when compared with control groups. Our data show that the
      pinealectomy facilitates the epileptogenic process that follows the long-lasting
      status epilepticus. This facilitation can be partially reverted by the
      simultaneous administration of melatonin.

PMID- 15862515
TI  - Clozapine, ziprasidone and aripiprazole but not haloperidol protect against
      kainic acid-induced lesion of the striatum in mice, in vivo: role of 5-HT1A
      receptor activation.
AB  - Excessive activation of non-NMDA receptors, AMPA and kainate, contributes to
      neuronal degeneration in acute and progressive pathologies, possibly including
      schizophrenia. Because 5-HT(1A) receptor agonists have neuroprotective properties
      (e.g., against NMDA-induced neurotoxicity), we compared the effects of the
      antipsychotics, clozapine, ziprasidone and aripiprazole, that are partial
      agonists at 5-HT(1A) receptor, with those of haloperidol, which is devoid of 5
      HT(1A) agonist properties, on kainic acid (KA)-induced striatal lesion volumes,
      in C57Bl/6N mice. The involvement of 5-HT(1A) receptors was determined by
      antagonist studies with WAY100635, and data were compared with those obtained
      using the potent and high efficacy 5-HT(1A) receptor agonist, F13714. Intra
      striatal KA lesioning and measurement of lesion volumes using cresyl violet
      staining were carried out at 48 h after surgery. F13714, antipsychotics or
      vehicle were administered ip twice, 30 min before and 3 1/2 h after KA injection.
      WAY100635 (0.63 mg/kg) or vehicle were given sc 30 min before each drug
      injection. Clozapine (2 x 10 mg/kg), ziprasidone (2 x 20 mg/kg) and aripiprazole
      (2 x 10 mg/kg) decreased lesion volume by 61%, 59% and 73%, respectively.
      WAY100635 antagonized the effect of ziprasidone and of aripiprazole but only
      slightly attenuated that of clozapine. In contrast, haloperidol (2 x 0.16 mg/kg)
      did not affect KA-induced lesion volume. F13714 dose-dependently decreased lesion
      volume. The 61% decrease of lesion volume obtained with F13714 (2 x 0.63 mg/kg)
      was antagonized by WAY100635. WAY100635 alone did not affect lesion volume. These
      results show that 5-HT(1A) receptor activation protects against KA-induced
      striatal lesions and indicate that some atypical antipsychotic agents with 5
      HT(1A) agonist properties may protect against excitotoxic injury, in vivo.

PMID- 15862516
TI  - Retinal projections to the midline and intralaminar thalamic nuclei in the common
      marmoset (Callithrix jacchus).
AB  - In this study, we report the identification of a hitherto not reported direct
      retinal projection to midline and intralaminar thalamic nuclei in the marmoset
      brain. After unilateral intravitreal injections of cholera toxin subunit B (CTb),
      anterogradely transported CTb-immunoreactive fibers and presumptive terminals
      were seen in the following thalamic midline nuclei: paraventricular, rhomboid,
      interanteromedial, and reuniens, and thalamic intralaminar nuclei: central
      medial, central lateral, central dorsal, and parafascicular. Studies employing
      sensitive tracers in other primate species are needed in order to verify the
      possible universality of these projections. Some of the possible functional
      correlates of the present data are briefly discussed. The present results may
      contribute to the elucidation of the anatomical substrate of the functionally
      demonstrated involvement of this midline/intralaminar thalamic nuclear complex in
      several domains that include arousal and awareness, besides specific cognitive,
      sensory, and motor functions.

PMID- 15862517
TI  - Characterizing learning deficits and hippocampal neuron loss following transient
      global cerebral ischemia in rats.
AB  - The 2-vessel-occlusion + hypotension (2VO + H) model of transient global cerebral
      ischemia results in neurodegeneration within the CA1 field of the hippocampus,
      but previous research has failed to demonstrate robust or reliable
      learning/memory deficits in rats subjected to this treatment. In the present
      study, sensitive behavioral protocols were developed in an effort to characterize
      the cognitive impairments following 2VO + H more precisely. Adult rats were
      exposed to 10 min of bilateral carotid occlusion with simultaneous hypotension.
      Following recovery, 2VO + H and control rats were subjected to a series of
      behavioral tests (locomotor activity, sensorimotor battery, water maze [cued,
      place, learning set], object recognition, and radial arm maze) over an extended
      recovery period followed by an assessment of neuronal loss in the dorsal
      hippocampus. The 2VO + H treatment was associated with long-lasting spatial
      learning deficits in the absence of other behavioral impairments and with
      neurodegeneration in dorsal hippocampal CA1. Water maze protocols that placed
      higher memory demands upon the rats (relatively "hard" vs. "easy") were more
      sensitive for detecting ischemia-induced deficits. We have shown that the use of
      appropriate behavioral tests (e.g., a relatively difficult place learning task)
      allowed for the observation of robust spatial learning deficits in a model
      previously shown to induce relatively subtle behavioral effects. Thus, the 2VO +
      H model induces both hippocampal neuronal loss and long-term learning deficits in
      rats, providing a potentially useful model for evaluating therapeutic efficacy.

PMID- 15862518
TI  - Effects of depression, cigarette smoking, and age on monoamine oxidase B in
      amygdaloid nuclei.
AB  - Altered concentrations of dopamine transporter and D2/D3 receptors have been
      observed in the amygdaloid complex of subjects with major depression. These
      findings are suggestive of neurochemical abnormalities in the limbic dopamine
      system in depression. Monoamine oxidase-B (MAO-B) is a key enzyme in the
      catabolism of biogenic amines, including dopamine, and alterations in this enzyme
      may underlie dopaminergic abnormalities associated with depression. The specific
      binding of [(3)H]lazabemide to MAO-B was measured in the right amygdaloid complex
      of 15 major depressive subjects and 16 psychiatrically normal controls. Subjects
      of the two study groups were matched as close as possible for age, sex, and
      postmortem interval. Examination of the regional distribution of MAO-B revealed
      lower [(3)H]lazabemide binding to MAO-B in the lateral and basal nuclei of the
      amygdala and higher binding in the medial nucleus. A modest elevation in binding
      to MAO-B observed in all amygdaloid nuclei in major depressive subjects as
      compared to control subjects failed to reach statistical significance. A
      significant decrease in binding to MAO-B was observed when cigarette smokers were
      compared to nonsmoking subjects. The amount of MAO-B binding positively
      correlated with the age of subjects in all nuclei investigated. A decreased
      amount of MAO-B in smokers further validates the pharmacological effect of
      tobacco smoke on this enzyme.

PMID- 15862519
TI  - Retrograde study of projections from the tuberomammillary nucleus to the dorsal
      raphe and the locus coeruleus in the rat.
AB  - In the first series of experiments, a retrograde tracer, WGA-apo-HRP-gold (WG),
      was injected into the dorsal raphe (DR) or the locus coeruleus (LC) and adenosine
      deaminase immunostaining was subsequently performed for the tuberomammillary
      nucleus (TMN) in order to investigate projections from the TMN to the two
      brainstem monoaminergic nuclei. Following rostral DR injections, the majority of
      retrogradely labeled cells were located in the dorsomedial and ventrolateral
      subdivisions of the TMN. At middle DR levels, midline injections resulted in
      labeling mainly in the ventrolateral subdivision, whereas lateral wing injections
      produced labeling mostly in ventral and caudal TMN subdivisions. When injections
      were made in the caudal DR, only a few cells were observed along the rostro
      caudal extent of the TMN. On the other hand, following rostral LC injections,
      labeled neurons were observed mainly in ventrolateral and ventral subdivisions of
      TMN. For principal LC injections, labeled cells were observed mostly in
      ventrolateral, ventral, and caudal TMN subdivisions, whereas for injections at
      caudal pole of LC, only a few cells were located along the rostro-caudal extent
      of the TMN. In the second series of experiments, an iontophoretic injection of
      fluorogold (FG) into the DR was paired with a pressure injection of WG into the
      LC to investigate the collateral distribution of TMN axonal fibers to DR and LC.
      Double-labeled cells were observed in ventrolateral, ventral, and caudal TMN
      subdivisions. The present study indicated that there exists a robust projection
      from the TMN to the DR or the LC and that some TMN neurons have axon collaterals
      projecting to both DR and LC. The TMN neurons with such axon collaterals might
      provide simultaneous, possibly more efficient, way of controlling the brainstem
      monoaminergic nuclei, thus influencing various sleep and arousal states of the
      animal.

PMID- 15862520
TI  - Progesterone regulation of catecholamine secretion from chromaffin cells.
AB  - Stress stimulates the adrenal medulla to rapidly secrete catecholamines (CAs),
      and the adrenal cortex to release progesterone (PROG), which may locally regulate
      stress-induced CA release. We used bovine chromaffin cells to investigate the
      effects of PROG on CA secretion. PROG dose-dependently inhibited CA secretion
      induced by nicotinic acetylcholine receptor (nAChR) agonist 1,1-dimethyl-4
      phenlypiperazinium iodide (DMPP) up to 77%. Pre-incubation with PROG up to 1 h
      increased this inhibition. 3alpha,5alpha-Tetrahydroprogesterone (3alpha,5alpha
      THP) and dexamethasone were less potent inhibitors. Patch-clamp techniques
      revealed that PROG co-applied with DMPP inhibited peak DMPP-induced current up to
      68% and with 3 min pre-incubation inhibited both peak and integrated current up
      to approximately 95%. Monitoring of FURA-2 showed that PROG similarly inhibited
      parallel changes in intracellular-free Ca(++) concentration. PROG also inhibited
      CA secretion elicited by elevated K(+) (38%), and, in single cells, suppressed
      Ca(++) current evoked by step depolarization, inhibiting amplitude by 15%, and
      reducing the time constant of current decay during depolarization by 57%. In
      contrast to the immediate inhibition of nicotinic current, inhibition of Ca(++)
      current became statistically significant only after 1 min exposure to PROG. PROG
      did not inhibit secretion stimulated by high Ca(++) perfusion of permeabilized
      cells. These data suggest that PROG inhibits CA secretion from chromaffin cells
      predominantly by rapidly inhibiting nAChRs, and by gradually enhancing the
      inactivation of voltage-dependent Ca(++) channels (VDCCs), but not by affecting
      secretory processes downstream of Ca(++) influx. This study supports a role for
      adrenocortical PROG in the regulation of CA secretion during stress.

PMID- 15862521
TI  - C1-C3 spinal cord projections to periaqueductal gray and thalamus: a quantitative
      retrograde tracing study in cat.
AB  - By far, the strongest spinal cord projections to periaqueductal gray (PAG) and
      thalamus originate from the upper three cervical segments, but their precise
      organization and function are not known. In the present study in cat, tracer
      injections in PAG or in thalamus resulted in more than 2400 labeled cells, mainly
      contralaterally, in the first three cervical segments (C1-C3), in a 1:4 series of
      sections, excluding cells in the dorsal column and lateral cervical nuclei. These
      cells represent about 30% of all neurons in the entire spinal cord projecting to
      PAG and about 45% of all spinothalamic neurons. About half of the C1-C3 PAG and
      C1-C3 thalamic neurons were clustered laterally in the ventral horn (C(1-3vl)),
      bilaterally, with a slight ipsilateral preponderance. The highest numbers of C(1
      3vl)-PAG and C(1-3vl)-thalamic cells were found in C1, with the greatest density
      rostrocaudally in the middle part of C1. A concept is put forward that C(1-3vl)
      cells relay information from all levels of the cord to PAG and/or thalamus,
      although the processing of specific information from upper neck muscles and
      tendons or facet joints might also play a role.

PMID- 15862522
TI  - Expression of groups I and II metabotropic glutamate receptors in the rat brain
      during aging.
AB  - Age-dependent changes in the expression of group I and II metabotropic glutamate
      (mGlu) receptors were studied by in situ hybridization, Western blot analysis and
      immunohistochemistry. Male Fisher 344 rats of three ages (3, 12 and 25 months)
      were tested. Age-related increases in mGlu1 receptor mRNA levels were found in
      several areas (thalamic nuclei, hippocampal CA3) with parallel increases in
      mGlu1a receptor protein expression. However, a slight decrease in mGlu1a receptor
      mRNA expression in individual Purkinje neurons and a decline in cerebellar mGlu1a
      receptor protein levels were detected in aged animals. In contrast, mGlu1b
      receptor mRNA levels increased in the cerebellar granule cell layer. Although
      mGlu5 receptor mRNA expression decreased in many regions, its protein expression
      remained unchanged during aging. Compared to the small changes in mGlu2 receptor
      mRNA levels, mGlu3 receptor mRNA levels showed substantial age differences. An
      increased mGlu2/3 receptor protein expression was found in the frontal cortex,
      thalamus, hippocampus and corpus callosum in aged animals. These results
      demonstrate region- and subtype-specific, including splice variant specific
      changes in the expression of mGlu receptors in the brain with increasing age.

PMID- 15862523
TI  - Interaction between neuropeptide Y and alpha-melanocyte stimulating hormone in
      amygdala regulates anxiety in rats.
AB  - Neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (alpha-MSH) have
      been implicated in pathophysiology of feeding and certain mood disorders,
      including anxiety and depression. Both the peptides are abundantly present in
      CNS, especially in the hypothalamus and amygdala. Although they are known to
      exert opposite effects, particularly with reference to anxiety, the underlying
      mechanisms are not known. We were interested in studying the interaction between
      these two peptides in the regulation of anxiety, within the framework of
      amygdala. We administered agents like NPY, alpha-MSH, selective melanocortin-4
      receptor (MC4-R) antagonist HS014 and NPY Y1 receptor agonist [Leu(31), Pro(34)]
      NPY, alone and in combinations, unilaterally in right amygdala of rats and
      measured the response using elevated plus maze test. While NPY and [Leu(31),
      Pro(34)]-NPY increased the time spent and number of entries in the open arms
      suggesting anxiolytic-like effects, alpha-MSH resulted in opposite responses.
      Anxiolytic-like effect of NPY (10 nM) or [Leu(31), Pro(34)]-NPY (5 nM) was
      significantly reduced following prior alpha-MSH (250 ng) administration. Co
      administration of HS014 (1 nM) and NPY (5 nM) or [Leu(31), Pro(34)]-NPY (1 nM) at
      subeffective doses evoked synergistic anxiolysis. Since the closed arm entries
      displayed by animals of all the groups were in a similar range, the effects might
      not be ascribed to the changes in general locomotor activity. These results
      suggest that endogenous alpha-MSH and NPY containing systems may interact in the
      amygdala and regulate exploratory behavior in an animal model of anxiety.

PMID- 15862524
TI  - Effects of midazolam on the expression of conditioned taste aversion in rats.
AB  - In conditioned taste aversion (CTA), the animals learn to avoid a taste substance
      (conditioned stimulus, CS) which was previously associated with visceral distress
      (unconditioned stimulus, US). The present study examined the effects of
      administration of midazolam (MDZ), a benzodiazepine agonist, after the
      acquisition of CTA on the expression of CTA. After ingestion of 0.5 M sucrose
      (CS) was paired with an intraperitoneal (i.p.) injection of 0.15 M LiCl (US),
      control rats showed strong CTA to the CS. However, a systemic injection of MDZ
      (1.5 mg/kg, i.p.) before the retention test prevented conditioned animals from
      rejecting the CS, but in the subsequent retention tests where the drug was not
      administrated, those animals again showed strong aversions to the CS. Aversive
      taste reactivity patterns to the intraorally infused sucrose and 0.3 M dl-alanine
      in the conditioned animals were also diminished by the similar injection of MDZ,
      but not by a serotonergic anxiolytic agent, buspirone (2.5 or 5.0 mg/kg, i.p.).
      General taste sensory deficit might not be induced by MDZ because the drug
      injection did not impair conditioned aversions to 0.2 M NaCl and 0.01 M HCl.
      Infusion of MDZ into the basolateral nucleus of the amygdala (BLA) also
      attenuated conditioned aversions to sucrose. These results suggest that systemic
      or intra-BLA administrations of MDZ impair the expression of CTA selectively to
      sweet-tasting substances, implying that a transient MDZ-induced CTA expression
      deficit is due to the enhancement of palatability of CSs with preferable tastes
      rather than general anxiolytic or amnesic effects of MDZ.

PMID- 15862525
TI  - Acute estrogen potentiates excitatory responses of neurons in rat hypothalamic
      ventromedial nucleus.
AB  - In a previous behavioral study, brief application of a membrane-limited estrogen
      to neurons in rat hypothalamic ventromedial nucleus (VMN) facilitated lordosis
      behavior-inducing genomic actions of estrogen. Here, electrophysiological
      recordings from single neurons were employed to characterize these membrane
      initiated actions. From rat hypothalamic slices, electrical activity was recorded
      from neurons in the ventrolateral VMN, the cell group crucial for estrogen
      induction of lordosis. In addition to the resting activity, neuronal responses to
      histamine (HA) and N-methyl-d-aspartate (NMDA) were also recorded before, during,
      and after a brief (10-15 min) application of estradiol (E, 10 nM). These two
      transmitters were chosen because their actions are mediated by different
      mechanisms: HA through G protein-coupled receptors and NMDA by ligand-activated
      ion channels. Vehicle applications did not affect either resting activity or
      neuronal responses. In contrast, acute E exposure modulated neuronal responses to
      transmitters, with no significant effect on the resting activity. It potentiated
      excitatory responses to HAs (20 out of 48 cells tested) and to NMDA (10 out of 19
      cells), but attenuated inhibitory responses to HA (3 out of 6 units). Both of
      these hormonal actions would increase VMN neuronal excitation. In separate
      experiments, neuronal excitation was found to be suppressed by anesthetics, which
      would block E's induction of lordosis when administered at the time of estrogen
      application. These data are consistent with the notion that increasing electrical
      excitation of VMN neurons can be a mechanism by which acute E exposure
      facilitates the lordosis-inducing genomic actions of estrogens.

PMID- 15862526
TI  - Melatonin enhances antinociceptive effects of delta-, but not mu-opioid agonist
      in mice.
AB  - This present study examines the effect of melatonin on antinociceptive action
      induced by opioid agonists in mice using the tail-flick test. When injected
      either by intraperitoneal (i.p.) (1, 5, 25 mg/kg) or by intracerebroventricular
      (i.c.v.) (0.25, 0.5, 1 mg/kg) routes, melatonin significantly enhanced the delta
      opioid agonist deltorphin I induced antinociception, but not mu-opioid agonist
      endomorphin-1. Further investigation showed that i.c.v. luzindole (0.5 mg/kg) (an
      antagonist of melatonin receptor) significantly antagonized the enhanced
      antinociceptive effect of i.c.v. melatonin. These results demonstrated that
      melatonin can specifically enhance the antinociception induced by specific opioid
      receptor agonist (i.e., delta opioid agonist) acting on melatonin receptor and
      that melatonin may have augmentation effect on analgesia with delta-, but not mu
      opioid agonists in mice.

PMID- 15862527
TI  - Blockade of the neuropeptide Y Y2 receptor with the specific antagonist BIIE0246
      attenuates the effect of endogenous and exogenous peptide YY(3-36) on food
      intake.
AB  - The gastrointestinal-derived hormone peptide YY (PYY) is released from intestinal
      L-cells post-prandially in proportion to calorie intake, and modulates food
      intake. Peripheral administration of PYY((3-36)) reduces food intake and body
      weight in rodents and suppresses appetite and food intake in humans. PYY((3-36))
      is hypothesised to inhibit food intake via activation of the auto-inhibitory pre
      synaptic neuropeptide Y (NPY) Y2 receptor (Y2R) present on arcuate (ARC) NPY
      neurons. We aimed to investigate the feeding effect of PYY((3-36)) following
      blockade of ARC Y2R, using the specific receptor antagonist BIIE0246, in the rat.
      We found that pre-treatment with BIIE0246 (1 nmol) into the ARC attenuated the
      reduction in feeding observed following intraperitoneal injection of PYY((3-36))
      (7.5 nmol/kg) (0-1 h food intake: BIIE0246/PYY((3-36)): 3.8 +/- 0.4 g; vs.
      Vehicle/PYY((3-36)): 2.7 +/- 0.2 g; P < 0.05). We found plasma PYY levels to be
      maximal at 120 min post-initiation of feeding. On investigation of the endogenous
      role of the Y2R, we found that ARC administration of BIIE0246 alone significantly
      increased feeding in satiated rats compared to vehicle-injected controls (0-1 h
      food intake: BIIE0246: 4.1 +/- 0.7 g; vs. vehicle: 1.7 +/- 0.7 g; P < 0.05),
      suggesting that Y2R antagonism disinhibits the NPY neuron thus stimulating
      feeding in otherwise satiated rats. These studies suggest that the Y2R plays an
      important role in post-prandial satiety and provide further insight into the
      mechanisms of action of PYY((3-36)).

PMID- 15862528
TI  - Mapping the neural circuit activated by alarm pheromone perception by c-Fos
      immunohistochemistry.
AB  - We previously reported that the alarm pheromones released from stressed male rats
      exaggerated both behavioral and autonomic (stress-induced hyperthermia) responses
      in recipient rats that were introduced into a novel environment. Subsequent
      experiments provided evidence that these alarm pheromones could be divided into
      two functionally different categories based on the site specificity and
      testosterone dependency of their production. However, the neural mechanisms
      underlying these behavioral and physiological responses remain unknown. In the
      present study, we examined Fos expression in 26 brain sites of the recipient rat
      60 min after the exposure to the pheromone that aggravated stress-induced
      hyperthermia. The alarm pheromone-exposed rats showed a concurrent increase in
      Fos expression, in contrast to control odor-exposed rats in the anterior division
      lateral and medial group of the bed nucleus of the stria terminalis,
      paraventricular nucleus, dorsomedial hypothalamic nucleus, anterodorsal medial,
      lateral and basolateral amygdaloid nucleus, ventrolateral periaqueductal gray,
      laterodorsal tegmental nucleus, and locus coeruleus. These results provide
      information about the neural mechanisms in response to a non-sexual pheromone,
      i.e., an alarm pheromone, and suggest that the perception of the alarm pheromone
      is related to stress-responsive brains structures, including the hypothalamus and
      brainstem, as well as to the amygdaloid nuclei.

PMID- 15862529
TI  - Perfusion and diffusion imaging in acute focal cerebral ischemia: temporal vs.
      spatial resolution.
AB  - High-resolution diffusion- (DWI) and perfusion-weighted (PWI) imaging may provide
      substantial benefits in accurate delineation of normal, ischemic, and at-risk
      tissue. We compared the capability of low (400 x 400 microm(2)) and high (200 x
      200 microm(2)) spatial resolution imaging in characterizing the spatiotemporal
      evolution of the ischemic lesion in a permanent middle artery occlusion (MCAO)
      model in rats. Serial measurements of cerebral blood flow (CBF) and the apparent
      diffusion coefficient (ADC) were performed. Lesion volumes were calculated by
      using viability thresholds or by visual inspection, and correlated with infarct
      volume defined by TTC staining at 24 h after MCAO. At the very early phase of
      ischemia, high-resolution resulted in a significantly larger ADC-derived lesion
      volume and a smaller PWI/DWI mismatch. At 3 h after MCAO, ADC and CBF lesions
      showed similar robust correlations with TTC-defined infarct volumes for both
      groups using previously established thresholds. When lesions were determined
      visually, low-resolution resulted in a substantial overestimation of TTC-defined
      infarct volume and a lower inter-observer reliability (r = 0.75), whereas high
      resolution produced an excellent correlation with TTC-defined infarct volume and
      inter-observer reliability (r = 0.96). In conclusion, high-resolution MRI
      resulted in substantial temporal averaging of the ischemic lesion during the
      early phase, but was clearly superior in visual determination of final infarct
      size. Low-resolution reasonably evaluated the temporal and spatial evolution of
      ischemia when thresholds were used.

PMID- 15862530
TI  - Effects of changes in pH on the afferent impulse activity of isolated cat muscle
      spindles.
AB  - Muscle spindle activity has been shown to decrease in the sustained contracting
      muscle. The effect has been assumed to result from a declining fusimotor drive.
      Since accumulation of metabolites including H(+), lactate and CO(2) might also
      affect the receptor in the fatiguing muscle, the impulse activity of muscle
      spindles isolated from the cat tenuissimus muscle was characterized under varying
      degrees of extracellular pH, thus excluding any effect on fusimotor activity,
      blood supply and extrafusal muscle fibers. The isolated receptor was exposed to
      bathing fluids of pH 6.4, 7.4 and 8.4, and afferent discharge activity was
      recorded from the spindle nerve. Both primary and secondary endings responded
      similarly to changes in pH. Resting discharge frequency usually decreased with
      decreasing pH and increased with increasing pH. A sudden break-off in activity
      was observed with about 40% of primary endings and about 30% of secondary endings
      at pH 6.4. Experiments with slow stretch stimulation indicated that this effect
      was caused by a rising threshold of firing at the encoder site of the endings.
      With brief ramp-and-hold stretches, we tested the effects of changes in pH on the
      dynamic and static sensitivity of primary and secondary endings. When pH was
      reduced from 7.4 to 6.4, the initial burst activity at the beginning of the ramp
      phase increased in primary and secondary endings and the dynamic response
      increased in secondary endings, demonstrating that the dynamic properties of
      muscle spindle endings were usually augmented in the acidic milieu. The static
      properties rose as well because the static index of both types of ending
      increased significantly. By contrast, dynamic and static properties of both
      primary and secondary endings decreased significantly, when pH was increased from
      7.4 to 8.4. The amplitude of tension that was measured during the passive stretch
      stimuli very slightly decreased in the acidic solution and very slightly
      increased in the alkaline solution. The decrease in the resting discharge
      activity at low pH supports those previous observations, which demonstrate a
      reduced peripheral input from muscle spindle afferents to the spinal motor nuclei
      during fatigue in the isometric contracting muscle. The present finding indicates
      that an attenuated afferent discharge is not only caused by a decreasing central
      activation of gamma-motorneurons, but may additionally be supported by a direct
      effect of protons on the muscle receptor itself. The accompanying augmentation of
      stretch sensitivity is suggested to correspond to the well-known increase in
      physiological tremor during exhaustive exercise.

PMID- 15862531
TI  - Behavioral effects of d-cycloserine in rats: the role of anxiety level.
AB  - It has been reported that the glutamatergic N-methyl-D-aspartate (NMDA) receptor
      is involved in stress responses and that anxiety is the primary response to
      stress. Although individual differences in anxiety levels of rats have been
      demonstrated by using the elevated plus-maze (PM) test, the role of NMDA receptor
      activity in such individuality of anxiety is not clear. Here, we examined whether
      low (LA) and high (HA) anxiety rats might respond differently to treatment with d
      cycloserine (DCS), a partial agonist of the glycine binding site located on NMDA
      receptors. Male Wistar rats were screened by using the PM and divided into LA and
      HA subgroups. On the next day, these rats were again tested in the PM, 30 min
      after the treatment with DCS (5, 10, or 30 mg/kg ip). Five days later, the rats
      were subjected to a 2-day forced swim (FS) test, receiving the DCS treatment
      again 30 min before the second day session. The PM data showed that DCS had
      anxiogenic effects in LA but not HA rats. The immobility of LA or HA rats in the
      FS test was not affected by DCS. The results indicate that the behavioral effects
      of DCS depend on the anxiety level of rats and have task-dependent behavioral
      consequences, suggesting that glycine binding sites on NMDA receptors are
      involved in individual differences of anxiety level.

PMID- 15862532
TI  - In vivo effects of local activation and blockade of 5-HT1B receptors on globus
      pallidus neuronal spiking.
AB  - Several morphological works have shown that the globus pallidus (GP) contains the
      highest density of 5-HT1B receptors within the telencephalon. However, the role
      of these receptors in the spiking of GP neurons in vivo is unknown. In the
      present work, we use single-unit extracellular recordings in the anesthetized rat
      to analyze changes in the firing rate of GP neurons evoked by local activation
      and blockade of 5-HT1B receptors. Intrapallidal administration of serotonin, or
      the serotonin uptake inhibitor fluoxetine, predominantly produced an excitatory
      effect in the basal firing rate of GP neurons. The 5-HT1B receptor agonist, L
      694,247, caused a dose-dependent excitatory effect on most pallidal neurons
      tested. Blockade of 5-HT1B receptors by intrapallidal application of methiothepin
      predominantly caused inhibition in GP neurons firing rate. Moreover, methiothepin
      diminished the excitatory effect evoked by L-694,247. Furthermore, local
      serotonin did not evoke significant changes in the basal firing rate of GP
      neurons in unilateral striatal lesioned rats. Taken all together, these results
      suggest that serotonin 5-HT1B receptors significantly contribute to the control
      of spiking of the rat GP neurons, and that the 5-HT1B receptors exerting this
      control are most likely localized in the striato-pallidal pathway.

PMID- 15862533
TI  - Effect of testosterone on functional recovery in a castrate male rat stroke
      model.
AB  - Both increased and decreased testosterone levels have been reported to correlate
      with poor outcome after acute ischemic stroke. The present study focused on the
      role of testosterone during recovery from neurological deficits in a rat focal
      ischemia model. Castrate male rats were subjected to behavioral tests after 90
      min of middle cerebral artery occlusion (MCAO). On day 7 post-MCAO, neurological
      deficit-matched rats were assigned to a treatment group implanted with
      subcutaneous testosterone pellets or a control group implanted with sham
      cholesterol pellets. After 4 weeks post-MCAO, the average infarct volume was not
      significantly different between the two groups. Rats in the testosterone group
      demonstrated significantly earlier improvement in neurological deficits and
      shortened latency of adhesive tape removal compared with the control group as
      analyzed by Wilcoxon signed ranks test. Walking on parallel bars improved in both
      groups with a trend towards early recovery observed in the testosterone group.
      Biased left body swings persisted during the test period in both groups post
      MCAO. Serum testosterone was within physiological levels in the treatment group
      but was not detectable in the control group by radioimmunoassay. GAP-43 and
      synaptophysin expression did not differ between groups. Less GFAP expression and
      reactive astrocyte hypertrophy were found around the infarct area in testosterone
      treated rats compared with control rats. In conclusion, testosterone replacement
      post-MCAO accelerated functional recovery in castrate rats, suggesting a
      potential therapeutic role for testosterone replacement in stroke recovery.

PMID- 15862534
TI  - Neuronal nitric oxide synthase and gonadal steroid interaction in the MPOA of
      male rats: co-localization and testosterone-induced restoration of copulation and
      nNOS-immunoreactivity.
AB  - Neuronal nitric oxide synthase (nNOS) in the medial preoptic area (MPOA) has been
      implicated in various physiological functions, including male rat copulation.
      Based on their apparent sensitivity to gonadal steroid manipulation, we
      hypothesized that nNOS cells contain steroid receptors, and the testosterone
      induced restoration of nNOS-immunoreactivity in castrates should accompany the
      restoration of copulation. In Experiment 1, we investigated co-localization of
      nNOS with the androgen receptor (AR) and the estrogen receptor alpha (ERalpha)
      using immunocytochemistry. We found regionally specific co-localizations of nNOS
      AR and nNOS-ERalpha. In Experiment 2, we investigated the relationship between
      MPOA nNOS-immunoreactivity (ir) and copulatory measures in the testosterone
      induced restoration paradigm in castrates. The restoration of various copulatory
      measures was accompanied by an increase in optical density of nNOS-ir, but not in
      the number of nNOS-ir cells. These data provide additional evidence supporting
      the role of MPOA nitric oxide in male rat copulation.

PMID- 15862535
TI  - Expression of ORL1 mRNA in some brain nuclei in neuropathic pain rats.
AB  - The present study was designed to investigate changes of opioid receptor like 1
      receptor (ORL(1), NOP) mRNA expression in some pain-related brain nuclei of
      neuropathic pain rats using in situ hybridization technique. Nociceptin/orphanin
      FQ (N/OFQ), the endogenous ligand of ORL(1), plays an important role in
      neuropathic pain through its receptor. There are ORL(1) mRNA expression in the
      nucleus of raphe magnus (NRM), ventrolateral periaqueductal gray (vlPAG) and
      dorsal raphe nucleus (DRN) of rat mesencephalon. In the sciatic nerve chronic
      constriction injury (CCI)-induced neuropathic pain model, a significant increase
      of ORL(1) mRNA expression was observed in these three regions on the 7th day
      after operation, and the changes lasted for 2 weeks. The result indicated that
      ORL(1) synthesis was increased in NRM, vlPAG and DRN of neuropathic pain rats,
      suggesting that ORL(1) was involved in nociceptive transmission of neuropathic
      pain.

PMID- 15862536
TI  - Substance P immunoreactive cell reductions in cerebral cortex of Niemann-Pick
      disease type C mouse.
AB  - Niemann-Pick disease type C (NPC) is characterized by progressive
      neurodegeneration and arises from mutations in the NPC1 gene. Cholesterol has
      received most attention in the pathogenesis of NPC, but normalizing lipid levels
      in humans or mouse does not prevent neurodegeneration. In NPC mouse, neuronal
      degeneration in the cerebellum is the most commonly detected change, and thus
      previous studies have tended to focus on the cerebellum, especially Purkinje
      cells. Although numerous peptides have been found in the mammalian central
      nervous system, little data on neurotransmitters in NPC are available, and
      information on neurotransmitter system abnormalities could explain the complex
      and characteristic deficits of NPC. Thus, we performed an immunohistochemical
      study on NPC mouse cortices to compare cell numbers exhibiting vasoactive
      intestinal polypeptide (VIP), neuropeptide Y (NPY), and substance P (SP)
      immunoreactivity. In terms of VIP and NPY-immunoreactive (ir) cell numbers in the
      cerebral cortex, SP-ir cells were significantly reduced by about 90% in NPC (-/-)
      versus NPC (+/+) mouse, and were also mildly decreased in frontal and parietal
      NPC (+/-) versus NPC (+/+) mouse cortex. This study demonstrates for the first
      time, reduced number of SP-ir cells in the NPC mouse cortex.

PMID- 15862537
TI  - Delta-opioid receptor-immunoreactive neurons in the rat cranial sensory ganglia.
AB  - Immunohistochemistry for delta-opioid receptor (DOR) was performed on the rat
      cranial sensory ganglia. The immunoreactivity was detected in 16%, 19% and 11% of
      neurons in the trigeminal, jugular and petrosal ganglia, respectively. The nodose
      ganglion was devoid of such neurons. DOR-immunoreactive (IR) neurons were mostly
      small to medium-sized (trigeminal, range = 62-851 microm(2), mean +/- SD = 359 +/
      175 microm(2); jugular, range = 120-854 microm(2), mean +/- SD = 409 +/- 196
      microm(2); petrosal, range = 167-1146 microm(2), mean +/- SD = 423 +/- 233
      microm(2)). Double immunofluorescence method revealed that all DOR-IR neurons
      were also immunoreactive for calcitonin gene-related peptide. The cutaneous and
      mucosal epithelia in the oro-facial region, tooth pulp, taste bud and carotid
      body were innervated by DOR-IR nerve fibers. In the brainstem, IR nerve terminals
      were located in the superficial medullary dorsal horn and dorsomedial part of the
      subnucleus oralis as well as the solitary tract nucleus. The present study
      suggests that DOR-IR neurons may be associated with nociceptive and/or
      chemoreceptive function in the cranial sensory ganglia.

PMID- 15862538
TI  - Evidence for peripherally antinociceptive action of propofol in rats: behavioral
      and spinal neuronal responses to subcutaneous bee venom.
AB  - In the present study, behavioral and in vivo electrophysiological methods were
      used to examine the peripheral effects of propofol on tonic ongoing pain-related
      responses produced by subcutaneous bee venom-induced inflammatory pain state.
      Local administration of 0.5 microg propofol produced significant suppression of
      the well-established ongoing pain responses in both conscious rats and dorsal
      horn nociceptive neurons. The locally antinociceptive action of propofol is not
      caused by systemic effect, because contralateral administration of the same dose
      of drug did not produce any effect. This result indicates that besides central
      actions, propofol has peripherally antinociceptive action as well.

PMID- 15862539
TI  - Neuroprotective effect of donepezil, a nicotinic acetylcholine-receptor
      activator, on cerebral infarction in rats.
AB  - This study evaluated the potential effect of donepezil, which is known as an
      acetylcholinesterase inhibitor used for treatment of Alzheimer's disease, against
      cerebral infarction induced by permanent left middle cerebral artery (MCA)
      occlusion. Donepezil was given orally in various regimens, prior to MCA occlusion
      in rats. Pretreatment with a single oral dose of donepezil (12 mg/kg), 2 h before
      ischemia, significantly attenuated cerebral infarction volume (165.5 +/- 105.3
      vs. 377.1 +/- 48.5 mm(3); P < 0.05). These neuroprotective effects were prevented
      by coinjection with mecamylamine, a nicotinic acetylcholine-receptor (nAChR)
      antagonist, indicating that protection was mediated by nAChR activation.

PMID- 15862540
TI  - Taurine prevents ammonia-induced accumulation of cyclic GMP in rat striatum by
      interaction with GABAA and glycine receptors.
AB  - Previously, we had shown that ammonium chloride (ammonia)-induced accumulation of
      cyclic GMP in the microdialysates of rat striatum is blocked by taurine. In this
      study, coinfusion with taurine of a GABAA receptor antagonist bicuculline or a
      glycine receptor antagonist strychnine (100 microM each), separately, restored
      ammonia-induced release of cGMP to the extracellular fluid to approximately 29%
      and 18% of the level measured in the absence of taurine, respectively.
      Simultaneous coinfusion of both antagonists or of 100 muM picrotoxin, which is an
      antagonist of both GABAA and Gly receptors, offsets most of the taurine block.
      Ammonia-induced accumulation of cyclic GMP was attenuated by approximately 12%
      upon coinfusion of a GABAA receptor agonist muscimol (100 microM). The results
      suggest that stimulation of both GABAA and glycine receptors is involved in the
      mechanism by which taurine limits the activation of the NMDA/NO/cGMP pathway by
      ammonia in the striatum.

PMID- 15862541
TI  - Gonadotropin-releasing hormone (GnRH) immunoreactive neurons in male mouse lemurs
      following removal of the vomeronasal organ.
AB  - Removal of the vomeronasal organ (VNO) in male mouse lemurs led to an increase in
      the number of immunoreactive gonadotropin-releasing hormone (GnRH) neurons in the
      medial preoptic area, compared to control males. No difference was found in the
      mediobasal hypothalamus. In this primate, which presents a fully functional VNO,
      the anterior part of the hypothalamus could be the major target for VNO-mediated
      regulation of GnRH function and the subsequent modulation of chemosensory
      dependent reproductive behavior.

PMID- 15862543
TI  - Neuropeptides and the control of food intake in fish.
AB  - The brain, particularly the hypothalamus, integrates input from factors that
      stimulate (orexigenic) and inhibit (anorexigenic) food intake. In fish, the
      identification of appetite regulators has been achieved by the use of both
      peptide injections followed by measurements of food intake, and by molecular
      cloning combined with gene expression studies. Neuropeptide Y (NPY) is the most
      potent orexigenic factor in fish. Other orexigenic peptides, orexin A and B and
      galanin, have been found to interact with NPY in the control of food intake in an
      interdependent and coordinated manner. On the other hand cholecystokinin (CCK),
      cocaine and amphetamine-regulated transcript (CART), and corticotropin-releasing
      factor (CRF) are potent anorexigenic factors in fish, the latter being involved
      in stress-related anorexia. CCK and CART have synergistic effects on food intake
      and modulate the actions of NPY and orexins. Although leptin has not yet been
      identified in fish, administration of mammalian leptin inhibits food intake in
      goldfish. Moreover, leptin induces CCK gene expression in the hypothalamus and
      its actions are mediated at least in part by CCK. Other orexigenic factors have
      been identified in teleost fish, including the agouti-related protein (AgRP) and
      ghrelin. Additional anorexigenic factors include bombesin (or gastrin-releasing
      peptide), alpha-melanocyte-stimulating hormone (alpha-MSH), tachykinins, and
      urotensin I. In goldfish, nutritional status can modify the expression of mRNAs
      encoding a number of these peptides, which provides further evidence for their
      roles as appetite regulators: (1) brain mRNA expression of CCK, CART,
      tachykinins, galanin, ghrelin, and NPY undergo peri-prandial variations; and (2)
      fasting increases the brain mRNA expression of NPY, AgRP, and ghrelin as well as
      serum ghrelin levels, and decreases the brain mRNA expression of tachykinins,
      CART, and CCK. This review will provide an overview of recent findings in this
      field.

PMID- 15862544
TI  - Growth hormone and insulin-like growth factors in fish: where we are and where to
      go.
AB  - This communication summarizes viewpoints, discussion, perspectives, and
      questions, put forward at a workshop on "Growth hormone and insulin-like growth
      factors in fish" held on September 7th, 2004, at the 5th International Symposium
      on Fish Endocrinology in Castellon, Spain.

PMID- 15862545
TI  - Developmental ontogeny of prolactin and its receptor in fish.
AB  - Prolactin (PRL) is a member of a family of structurally similar proteins which
      includes growth hormone (GH) and somatolactin (SL) in teleost fish. The genes
      encoding these proteins are expressed principally in the pituitary gland and
      sequence analysis reveals they share considerable similarity. GH, PRL, and SL
      bring about their physiological action by binding to specific receptors localised
      in the membrane of cells in target tissue. The PRL receptor (PRLR) and GH
      receptor (GHR) have been identified in a number of teleosts but the SL receptor
      remains to be characterised. On hormone binding, receptors dimerise, and signal
      transduction occurs via the JAK/STAT signalling pathway. The principal action of
      PRL in fish is freshwater osmoregulation, although it has also been implicated in
      reproduction, behaviour, growth, and immunoregulation. The role of PRL in early
      development and metamorphosis is well established, respectively, in mammals and
      amphibians, although its role in fish is not so well known. Studies have shown
      that PRL mRNA and protein are restricted to the developing pituitary gland in
      fish embryos and larvae. PRLR mRNA and protein is also present in fish embryos
      and has a widespread tissue distribution in larvae. The levels of PRLR and PRL
      mRNA vary throughout embryonic and early larval development. The potential role
      of PRL in fish embryos and larvae is considered in relation to their
      physiological status.

PMID- 15862546
TI  - Fish FSH receptors bind LH: how to make the human FSH receptor to be more fishy?
AB  - In mammals, the interactions between glycoprotein hormones and their cognate
      receptors are highly specific; unintended cross-reactivity under normal
      physiological conditions has not been observed. The interactions between fish
      gonadotropins and their receptors, on the other hand, appeared to be less
      discriminatory. For example, the catfish follicle-stimulating hormone (FSH)
      receptor was highly responsive to both catfish luteinizing hormone (LH) and
      catfish FSH. Similarly, the FSH receptor of coho salmon bound both salmon FSH and
      LH. In contrast, LH receptors of both species were found to be rather specific
      for their cognate LH. This paper intends to summarize the current situation with
      special emphasis to our comparative structure-function studies that aim at
      elucidating the molecular basis of ligand selectivity (in mammals) and ligand
      promiscuity (in fish).

PMID- 15862547
TI  - Roles of insulin-like growth factor (IGF) binding proteins in regulating IGF
      actions.
AB  - The insulin-like growth factor (IGF) system is an evolutionarily conserved
      signaling pathway that is composed of two IGF ligands, two IGF receptors, and six
      IGF binding proteins. Studies in a variety of species suggest that the IGF
      signaling system plays a fundamental role in regulating embryonic growth and
      differentiation as well as in maintaining homeostasis in the adults. In
      extracellular fluids, IGFs are present in a complex with an IGF-binding protein
      (IGFBP). These IGFBPs are traditionally thought to function as carrier proteins
      and regulate circulating IGF turnover, transport, and distribution. Locally
      expressed IGFBPs can also inhibit and/or potentiate IGF activities. Recent
      studies have shown that some IGFBPs, in particular IGFBP-3 and -5, possess
      intrinsic biological activities and can act through IGF-independent mechanisms.
      In this article, we provide a brief overview of our current understanding of the
      IGF signaling system with particular reference to IGFBPs.

PMID- 15862548
TI  - The evolution of neuroendocrine peptides.
AB  - The genomes of extant vertebrates have been shaped by a series of whole genome
      and individual gene duplication events. The 2R hypothesis, which postulates that
      two whole genome duplications occurred in relatively rapid succession very early
      in chordate evolution, is gaining increasing acceptance. A further entire genome
      duplication is believed to have occurred in the ancestral fish lineage
      approximately 320-350 Myr ago, as well as more recent independent
      tetraploidization events, mostly but not exclusively, in particular teleost and
      amphibian lineages. Superimposed upon these whole genome duplications are tandem
      or segmental duplications of individual genes or groups of genes that have taken
      place at different rates in the various vertebrate lineages. The majority of
      duplicated genes become pseudogenes or are deleted but some may evolve to encode
      components with new functional roles. Genes encoding members of neuropeptide Y-
      and tachykinin-families are associated with the HOX-bearing chromosomes and these
      systems provide examples of duplication events that have led to rapid evolution
      of the duplicated gene which has occasionally produced peptides, such as
      pancreatic polypeptide, seminalplasmin and hemokinin-1, with new biological
      functions.

PMID- 15862549
TI  - Relationships between aromatase and estrogen receptors in the brain of teleost
      fish.
AB  - Teleost fish are known for exhibiting a high aromatase activity mainly due to the
      expression of the cyp19b gene, encoding aromatase B (AroB). Recent studies based
      on both in situ hybridization and immunohistochemistry have demonstrated in three
      different species that this activity is restricted to radial glial cells. In
      agreement with measurements of aromatase activity, such aromatase-expressing
      cells are more abundant in the telencephalon, preoptic area, and mediobasal
      hypothalamus, although positive cells are also found in the midbrain and
      hindbrain. Comparative distribution of AroB and estrogen receptor (ERalpha,
      ERbeta1, and ERbeta2) expression indicates that the preoptic region and
      hypothalamus are major target for locally produced estradiol (E2) which is likely
      involved in controlling expression of genes implicated in neuroendocrine
      regulations. However, AroB and ER have never been reported to be co-expressed in
      the same cells which is intriguing given that, at least in some species, AroB is
      strongly up-regulated by E2 itself in agreement with the presence of an estrogen
      responsive element (ERE) in the proximal promoter of the cyp19b gene. In vivo
      data in zebrafish have shown that E2 up-regulates AroB only in radial glial
      cells. This is in agreement with in vitro transfection experiments indicating
      that this ERE is functional, but not sufficient, as the E2 regulation of AroB
      only occurs in glial cell contexts, suggesting a cooperation between ER and so
      far unidentified glial-specific factors. These data also suggest that radial
      glial cells may express low amounts of ER that escaped detection until now. The
      expression of AroB in radial cells, well known for their roles in neurogenesis
      and now considered as progenitor cells, suggests that local E2 production within
      these cells could influence the well-documented capacity of the brain of teleosts
      to grow during adulthood.

PMID- 15862550
TI  - Sequence analysis, endocrine regulation, and signal transduction of GnRH
      receptors in teleost fish.
AB  - Three gonadotropin-releasing hormones (GnRHs) and three cognate receptors have
      been identified in vertebrates, with distinct distributions and functions.
      According to their sequences, the receptors can be grouped into distinct classes:
      types I, II, and III. One branch contains all type-I GnRH receptors (GnRH-R-I)
      from mammals and fish; another branch clusters mainly amphibian and human type-II
      GnRH receptors; and a third branch includes evolved fish, mainly perciform
      species, type-III GnRH receptors. Taken tilapia GnRH receptors as a model, the
      present study summarizes the information regarding the amino-acid residues
      assumed to be involved in the receptors' structure, binding, activation, and
      intracellular signal transduction, including arrangement of the disulfide bonds,
      glycosylation sites, coupling to G proteins, and protein kinase A or protein
      kinase C phosphorylation sites.

PMID- 15862551
TI  - Developmental role of GnRH and PACAP in a zebrafish model.
AB  - GnRH is expressed early in development long before reproduction begins. To
      determine whether GnRH has a role in development, gene knockdown with morpholinos
      was used in one-cell zebrafish embryos to block translation of gnrh mRNA into
      protein. Gene knockdown of gnrh2, gnrh3 or both at the one-cell stage resulted in
      a high percentage of embryos at 24-48 h with a defective mid-hindbrain boundary
      and underdeveloped eyes; a small percentage of embryos at 72 h had a defective
      heart. In similar studies on GHRH-PACAP, gene knockdown resulted in a smaller
      brain and eyes, but a normal-appearing heart. The evidence supports a role for
      the three neuropeptides in early development.

PMID- 15862552
TI  - Trends in the evolution of the proopiomelanocortin gene.
AB  - The POMC gene is perhaps the most extensively studied member of the
      opioid/orphanin gene family. In Phylum Chordata this gene has been characterized
      in representatives of every class within the Gnathostomata, as well as in one
      representative agnathan vertebrate, the marine lamprey. This review provides a
      systematic overview of trends in the evolution of the melanocortins (ACTH/alpha
      MSH, beta-MSH, gamma-MSH, and delta-MSH) and beta-endorphin in gnathostomes, and
      advances the hypothesis that the appearance of gamma-MSH occurred early in the
      radiation of the gnathostomes. A summary of the extensive work on POMC genes in
      the marine lamprey is also provided, as well as a reevaluation of the conserved
      regions in the sequence of CLIP (corticotropin-like-intermediate lobe peptide) in
      the POMC sequences of the various groups of gnathostomes.

PMID- 15862553
TI  - The GRAFS classification system of G-protein coupled receptors in comparative
      perspective.
AB  - The super-family of G-protein coupled receptors (GPCRs) is one of the largest
      groups of proteins in vertebrate species. The receptors are very diverse in
      structure and function but they still share some common structural elements. Our
      recent phylogenetic studies indicate that most human GPCRs can be grouped into
      five main families named; Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, and
      Secretin, forming the GRAFS classification system. The rhodopsin family is the
      largest and forms four main groups termed alpha, beta, gamma, and delta with 13
      sub-branches. We have evidence that the main families of the GRAFS classification
      system arose prior to the split of nematodes from the lineage leading to
      chordates. The major part of all GPCRs in mammalian, fish, tunicate, insect, and
      nematode species belong to the GRAFS families. The evolution of GPCRs in
      different phylogenetic branches are, however, very variable as some of the
      branches are specific for certain lineages such as vertebrates or mammals, while
      others are found in a much larger variety of species. In this review, we provide
      an insight in several studies that are being performed to elucidate the
      evolutionary history of the GPCR family.

PMID- 15862554
TI  - Genetic, endocrine, and environmental components of sex determination and
      differentiation in the European sea bass (Dicentrarchus labrax L.).
AB  - The European sea bass (Dicentrarchus labrax L.) is a differentiated gonochoristic
      marine teleost of the family Moronidae (closely related to the hermaphrodites of
      the family Serranidae), where many juvenile males exhibit intratesticular
      oocytes, suggesting a certain sexual lability. Like most fish, the sea bass does
      not have recognizable heterochromosomes or sex-linked markers but there are clear
      parental effects on the sex ratios. The data available so far indicate that the
      proportion of females resulting from individual crossings may range from as
      little as 1 to about 70%. Sex differentiation proceeds in a caudo-cranial fashion
      and starts when fish reach 8-9 cm standard length (usually about 200 days post
      hatching, dph, under typical rearing conditions), with females differentiating
      first. Both forms of aromatase have been cloned in this species and their
      temporal expression has been studied. Brain aromatase is detectable already in
      the larval stages but its involvement in sex differentiation is not yet clear.
      The ovarian form increases after 100 dph before ovarian differentiation, with
      high levels in females and basal levels in males. Thus, ovarian aromatase seems
      to be involved in female differentiation. On the other hand, androgen receptor
      (AR) gene expression levels show the opposite pattern, with higher levels in
      males than in females. It is not yet known whether androgens are necessary for
      testicular differentiation or rather they are the result of it. Of the several
      environmental factors tested, temperature is the only one that has been shown to
      be able to clearly influence sex ratios. Larval and juvenile sea bass reared in
      captivity at high temperature usually develop as males. Recent research suggests
      that the high incidence of males under aquaculture conditions is due to the high
      water temperature used, and that the effects of temperature would be mediated by
      an inhibition of aromatase mRNA expression and activity in genotypic females.
      However, other effects of temperature mediated through alterations in
      developmental rates cannot be discarded. This paper reviews the current knowledge
      on sex determination and differentiation in the sea bass and suggests some
      directions for future research.

PMID- 15862555
TI  - Muscle growth patterns and regulation during fish ontogeny.
AB  - In fish, the skeletal muscle of the trunk and the tail derives from the somites
      which form in the paraxial mesoderm in a rostro-caudal sequence. The development
      of the fish myotome begins with the onset of myogenic regulatory factors
      expression and continues with the formation of a distinct superficial layer of
      slow muscle fibres that covers a bulk of fast muscle fibres located in the deep
      portion of the myotome. Muscle fibres of the slow-twitch lineage originate in
      fish embryos from adaxial cells, a distinct subpopulation of the paraxial
      mesoderm that flanks the notochord. During the early maturation of the somite
      these adaxial cells migrate away from the notochord towards the lateral part of
      the somite where they form the superficial slow fibres. Lateral presomitic cells
      that remain deep in the myotome differentiate into fast muscle fibres. Morphogens
      of the hedgehog family secreted by the notochord have a pivotal role in inducing
      the slow-twitch lineage. In late embryos, additional fibres are added from
      discrete germinal zones situated at the ventral and dorsal extremes of the
      developing myotome. This regionalised process has been termed "stratified
      hyperplasia." In fish which grow to a large final size this is followed by a
      mosaic hyperplastic process that leads to the formation of new fibres throughout
      the whole myotome. Current knowledge about the endocrine and autocrine factors
      that potentially regulate the proliferation and the differentiation of muscle
      cells within the embryonic and larval fish myotome is reviewed.

PMID- 15862556
TI  - Regulation of somatostatins and their receptors in fish.
AB  - The multifunctional nature of the somatostatin (SS) family of peptides results
      from a multifaceted signaling system consisting of many forms of SS peptides that
      bind to a variety of receptor (SSTR) subtypes. Research in fish has contributed
      important information about the components, function, evolution, and regulation
      of this system. Somatostatins or mRNAs encoding SSs have been isolated from over
      20 species of fish. Peptides and deduced peptides differ in their amino acid
      chain length and/or composition, and most species of fish possess more than one
      form of SS. The structural heterogeneity of SSs results from differential
      processing of the hormone precursor, preprosomatostatin (PPSS), and from the
      existence of multiple genes that give rise to multiple PPSSs. The PPSS genes
      appear to have arisen through a series of gene duplication events over the course
      of vertebrate evolution. The numerous PPSSs of fish are differentially expressed,
      both in terms of the distribution among tissues and in terms of the relative
      abundance within a tissue. Accumulated evidence suggests that nutritional state,
      season/stage of sexual maturation, and many hormones [insulin (INS), glucagon,
      growth hormone (GH), insulin-like growth factor-I (IGF-I), and 17beta-estradiol
      (E2)] regulate the synthesis and release of particular SSs. Fish and mammals
      possess multiple SSTRs; four different SSTRs have been described in fish and
      several of these occur as isoforms. SSTRs are also wide spread and are
      differentially expressed, both in terms of distribution of tissues as well as in
      terms of relative abundance within tissues. The pattern of distribution of SSTRs
      may underlie tissue-specific responses of SSs. The synthesis of SSTR mRNA and SS
      binding capacity are regulated by nutritional state and numerous hormones (INS,
      GH, IGF-I, and E2). Accumulated evidence suggests the possibility of both tissue-
      and subtype-specific mechanisms of regulation. In many instances, there appears
      to be coordinate regulation of PPSS and of SSTR; such regulation may prove
      important for many processes, including nutrient homeostasis and growth control.

PMID- 15862557
TI  - A quantitative real-time RT-PCR assay for European eel tyrosine hydroxylase.
AB  - Dopamine (DA) plays a key inhibitory role in pubertal development of the European
      eel, but how DAergic neuronal activity is regulated is not known in this species.
      In order to investigate the regulation of DA inhibition at the molecular level,
      we developed a quantitative real-time RT-PCR (qrtRT-PCR) assay, using the Light
      Cycler system, for the expression of eel tyrosine hydroxylase (TH), the rate
      limiting enzyme in catecholamine biosynthesis. Two different reference genes were
      compared: the previously cloned eel cytochrome b, and eel acidic ribosomal
      phosphoprotein P0, the latter of which we cloned and partly sequenced. To further
      validate the assay, different methods of total RNA extraction were tested and
      compared. When applied to cDNA extracted from dissected brains of juvenile eels,
      the expression of TH was highest in the olfactory bulb, followed by the
      telencephalon including preoptic area, and the di-/mesencephalic areas excluding
      the optic lobes. TH expression in the optic lobes and in the medulla oblongata
      was low, whereas no expression could be detected in corpus cerebellum. This
      distribution pattern is in agreement with earlier studies on TH in the eel using
      immunohistochemistry, RT-PCR, and Northern blotting. The developed qrtRT-PCR
      assay provides a new tool for understanding the mechanisms regulating central DA
      inhibition of puberty in juvenile eels.

PMID- 15862558
TI  - Transcriptional analysis of testis maturation using trout cDNA macroarrays.
AB  - The project seeks to identify genes involved in key stages of trout
      spermatogenesis and their regulation. Within the framework of the French project
      of farm animal genomics (AGENAE) we produced an original normalised trout testis
      cDNA library and obtained 1152 trout ESTs corresponding to 967 potential genes.
      To study the expression of those genes throughout first stages of
      spermatogenesis, we used nylon macroarray. Gonads in stage of immaturity (stage
      I), or at initiation of spermatogonial proliferation (stage II), meiosis (stage
      III) or spermiogenesis were selected by histological analysis. Total RNA was
      extracted and then used to produce complex targets labelled with [33P]dCTP and
      hybridised with cDNA arrays. After filtering and normalisation of hybridisation
      signals, genes presenting differential expression as revealed by ANOVA analysis
      were submitted to k-means clustering and hierarchical classification. Genes were
      separated into five clusters which presented distinct profiles. One cluster
      overexpressed in stage I could be involved in the initial events of
      spermatogenesis as seminiferous tubule organisation. The second cluster displays
      a transient increase at the beginning of testicular recrudescence (stage II).
      Three other clusters group several genes involved in cell proliferation and
      protein synthesis and modification. One is particularly down-expressed during
      stage I, the two others show increased expression during stages III and IV and
      appear to be involved in spermatogonial and meiotic proliferation and in protein
      metabolism linked to cellular growth. This allows us to plan further experiments
      to better understand the functional implication of some of the genes that are
      found to be significantly regulated like CDC2, hematological and neurological
      expressed gene 1-like protein, HCDI protein, Mago Nashi, a BMP-like, and a
      steroid receptor binding protein. These data demonstrate the applicability of the
      array based technology using our trout cDNA arrays and highlight genes that are
      potential targets for the control of puberty and fertility in farmed fish.

PMID- 15862559
TI  - Ontogeny of osteonectin expression in embryos and larvae of sea bream (Sparus
      auratus).
AB  - Osteonectin (OSN) is a glycoprotein which is implicated in development, bone
      formation and mineralisation, tumorigenesis, angiogenesis, and wound healing.
      Regulation of its expression by hormones may be one of the mechanisms by which
      the endocrine system affects bone metabolism. As a first step to understanding
      OSN function in fish, the gene expression of the recently cloned cDNA for sea
      bream, Sparus auratus, osteonectin (sbOSN) was characterised during embryonic and
      larval development. sbOSN mRNA was first detected by semi-quantitative reverse
      transcription-polymerase chain reaction in embryos at early gastrula and its
      expression increased continuously until hatch, after which it decreased until 15
      days post-hatch (dph), increased transiently until 24 dph and decreased
      thereafter. In situ hybridisation showed it had a differential tissue
      distribution which was age dependent. In general, sbOSN mRNA was identified in
      cartilaginous and calcified structures of both dermal and endochondral origin but
      its expression was not restricted to the skeleton. sbOSN transcripts were also
      detected in the skin, perichordal sheath, nerve cord, and kidney tubules.

PMID- 15862560
TI  - A peak in gh-receptor expression is associated with growth activation in Atlantic
      salmon vertebrae, while upregulation of igf-I receptor expression is related to
      increased bone density.
AB  - Growth hormone (GH) and insulin-like growth factor-I (IGF-I) play major roles in
      the endocrine regulation of fish growth, but their interdependency and mode of
      action has not been well elucidated. The GH-IGF-I system is essential for normal
      vertebral growth in mouse, but this has not been studied in fish. To study the
      interplay between GH, IGF-I, and their receptors, postsmolt Atlantic salmon were
      studied during spring growth (January-June 2003). From January to June, fish were
      sampled regularly for plasma and vertebral bone. The vertebra was collected from
      the same anterior-posterior position. The growth hormone receptor (ghr) (There is
      no determined nomenclature of salmon genes but we stick to the nomenclature which
      is consequent for zebrafish, where all gene names are named with small letters
      and in italic.) expression in the vertebrae peaked in the end of February
      coinciding with high levels of plasma GH and IGF-I, and an increase of vertebral
      growth rate. From April to June, plasma IGF-I levels decreased together with ghr
      expression in the vertebrae, while plasma GH did not decrease. In May and June,
      expression of the igf-I receptor (igf-Ir) increased 4- to 5-fold, which coincided
      with an increase in bone density. The changes seen in gene expression of the IGF
      I and GH receptors suggest that these hormones are involved in vertebral growth
      and bone density.

PMID- 15862561
TI  - Photoperiod influences growth rate and plasma insulin-like growth factor-I levels
      in juvenile rainbow trout, Oncorhynchus mykiss.
AB  - The effect of different photoperiod regimes and the subsequent influence of
      melatonin on growth and insulin-like growth factor-I (IGF-I) were assessed in
      juvenile rainbow trout. In Experiment 1, triplicate groups of all female
      underyearling rainbow trout were exposed to one of three photoperiods; simulated
      natural photoperiod (SNP), constant short-days (LD 8:16), or constant long-days
      (LD 18:6) from June to December 2000 under ambient water temperatures. Fish
      exposed to LD 18:6 grew to a significantly heavier mean weight than the other
      treatments. Regression analysis showed a strong correlation between circulating
      plasma IGF-I, growth rate and temperature. Furthermore, it was apparent that fish
      exposed to LD 18:6 expressed significantly higher circulating levels of IGF-I. In
      a second experiment, duplicate groups of all female yearling trout were exposed
      to one of three photoperiods; SNP, LD 8:16, or constant light (LL), with sub
      groups receiving either a slow-release melatonin implant (18 mg), sham implant or
      left intact (control). LL increased growth rate in controls, reaching a
      significantly greater weight than SNP or LD 8:16 photoperiods but did not affect
      circulating IGF-I levels. Melatonin implants reduced growth rate in all
      photoperiod treatments below that of their respective controls but again did not
      affect circulating IGF-I levels. No differences in growth rate were found in
      implanted fish between photoperiods suggesting that a diel cycle of melatonin is
      necessary for the perception of daylength. These results would indicate that
      extended photoperiods (LD 18:6) may cause direct photostimulation of growth
      through up-regulation of IGF-I production. In contrast, in the absence of a
      changing diel melatonin signal, growth appeared to be maintained by a possible
      underlying endogenous rhythm, which was phase advanced under LL, as such plasma
      IGF-I levels simply reflected growth rate rather than photostimulation of the
      somatotropic axis. Overall, these findings indicate that measuring plasma IGF-I
      may be a useful tool for studying environmental influences on growth in rainbow
      trout.

PMID- 15862562
TI  - Ontogeny of the thyroid hormones and cortisol in the gilthead sea bream, Sparus
      aurata.
AB  - The aim of the study was to elucidate the pattern of changes in the whole body
      concentrations of thyroid hormones (TH) and cortisol in eggs, pre-larvae, and
      larvae in the gilthead sea bream, Sparus aurata. The ontogeny of these hormones
      was related to specific morphological characteristics that characterize early
      development. TH and cortisol were detected in substantial amounts in the eggs of
      sea bream. T3 concentration in eggs was found to be higher than that of T4 (T3,
      4.02+/-0.38 ng g-1; T4, 1.63+/-0.28 ng g-1), as it is often observed in marine
      teleosts. T4 decreased until hatching (T4, 1.01+/-0.58 ng g-1), while T3 reached
      a minimum at the time of first feeding (T3, 0.19+/-0.02 ng g-1). As development
      proceeded, both hormones displayed a similar pattern of changes with increasing
      concentrations until the completion of metamorphosis (T3, 15.84+/-2.92 ng g-1;
      T4, 9.78+/-2.39 ng g-1), indicating that the hypothalamo-adenohypophysial-thyroid
      axis begins to function soon after first feeding. The pattern of changes of
      cortisol (F) concentration was almost parallel to that of T4, starting from 0.83
      ng g-1 in eggs. Minimum F concentration was observed at hatching (0.39+/-0.03 ng
      g-1) and maximum at melanophores and scale formation (14.82+/-2.71 and 14.82+/
      3.12 ng g-1, respectively). Results provide data for the first time on the
      ontogeny of thyroid hormones and cortisol during the early development in sea
      bream and are in agreement with results in other fish species for an important
      action of TH during early development.

PMID- 15862563
TI  - Duplication of growth hormone receptor (GHR) in fish genome: gene organization
      and transcriptional regulation of GHR type I and II in gilthead sea bream (Sparus
      aurata).
AB  - Nucleotide sequences encoding for functional growth hormone receptors (GHR) are
      now available in salmonids (coho and masu salmon) and other fish orders. Several
      authors have hypothesized a divergent evolution of salmonid GHRs, but the recent
      finding that a trout cDNA is related to non-salmonid (GHR type I) rather than to
      salmonid GHRs (GHR type II) points out a possible duplication of actively
      transcribed GHR genes. To address this issue, we search by RT-PCR for GHR type II
      in trout, gilthead sea bream, European sea bass, and turbot. Both in trout and
      gilthead sea bream, a cDNA sequence with all the characteristic features of masu
      and coho salmon GHRs (GHR type II) was found. Similarly, in European sea bass, a
      cDNA encoding for the intracellular domain of GHR type II was reported. No
      positive results were found in turbot, but searches in genome databases of fugu
      and zebrafish identified DNA sequences with a significant similarity to fish GHR
      type I and II, which are more related each other than to GHRs of tetrapods. Gene
      organization is, however, highly conserved through the evolution of vertebrates,
      and eight exons homologous to exons 2 and 4-10 of mammals were found in fish
      GHRs. Transcriptional regulation of GHR type I and II was also addressed by means
      of real-time PCR assays in gilthead sea bream. In liver and adipose tissue, GHR
      type I was the most abundant transcript, but the expression of GHR type I and II
      was practically equal in skeletal muscle. Both in liver and adipose tissue, the
      two GHRs were down-regulated by fasting. In skeletal muscle, the expression of
      GHR type I remained unaltered in fasted fish, whereas a 2- to 3-fold increase was
      found for GHR type II. All this provides suitable evidence for a tissue-specific
      regulation of fish GHRs, but further research is needed to determine whether
      these duplicated genes are evolved in a new or redundant fashion.

PMID- 15862564
TI  - Membrane-bound progestin receptors in channel catfish and zebrafish ovary:
      changes in gene expression associated with the reproductive cycles and hormonal
      reagents.
AB  - Membrane-bound progestin receptors (mPRs) are potential intermediaries in meiotic
      maturation of fish oocytes and other physiological processes. In this study, gene
      expression of the mPRs in the ovary of catfish and zebrafish during the
      reproductive cycle and the hormonal regulation of the expression were
      investigated. The transcript abundance of catfish mPRalpha gradually increased in
      conjunction with ovarian growth and then decreased prior to spawning period
      whereas the ovarian gene expression of mPRbeta varied little throughout the
      reproductive cycle. In contrast, mPRgamma gene expression peaked early in the mid
      vitellogenic stage. The transcript abundance of zebrafish mPRalpha and beta was
      low in ovarian follicles at early stages of oogenesis and gradually increased
      after the onset of vitellogenic growth and, thereafter, the gene expression did
      not vary. Gonadotropic treatment did not modulate the ovarian expression of
      mPRalpha and beta genes in either catfish or zebrafish. On the other hand,
      exposure to 17,20beta-dihydroxy-4-pregenen-3-one (the maturation-inducing steroid
      in this species) resulted in the down-regulation of mPRalpha in catfish ovary
      whereas gene expression was significantly induced by estradiol-17beta. Taken
      together, these findings suggest that gonadotropin-induced final oocyte
      maturation may not require an induction of mPR(s) expression or that the
      gonadotropin stimulates mPR protein production at the post-transcriptional level,
      presuming these receptors are indispensable for oocyte maturation.

PMID- 15862565
TI  - Enhancing spawning in the grey mullet (Mugil cephalus) by removal of dopaminergic
      inhibition.
AB  - A dot-blot immunoassay for the detection of vitellogenin (Vtg) in plasma of adult
      grey mullet (Mugil cephalus) was developed. The assay identified the sex of the
      tested fish prior to detectable gonadal development, enabling the establishment
      of broodstock at the desired ratio of 7:4 females to males. This broodstock was
      maintained under natural photoperiod, and used to study the relative effect of
      gonadotropin-releasing hormone (GnRH) and dopamine antagonists on oocyte
      maturation and ovulation, as well as the effect of 17alpha-methyltestosterone
      (MT) on spermiation. Three groups of females were treated with: (i) a single
      injection of dopamine antagonist, domperidone (Dom), (ii) GnRH analog (GnRHa)
      administered via ethylene-vinyl acetate copolymer (EVAc) slow-release implants or
      (iii) a combination of both Dom and GnRHa. Males were treated with MT,
      administered via EVAc slow-release implants. An additional group of untreated
      fish was used as a control. The Dom treatment proved to be more potent than the
      GnRHa treatment, and did not differ significantly from the combined treatment.
      The Dom and Dom+GnRHa treatments accelerated oocyte development and increased
      plasma estradiol levels equally, whereas the GnRHa treatment did not vary
      significantly from the control. MT was found to be a potent spermiating agent,
      which enhanced steady milt production in all treated males. In contrast, no
      spontaneous spermiation occurred in untreated males. Plasma 11-ketotestosterone
      (11-KT) levels were significantly higher in MT-treated males than in the
      controls. Interestingly, MT-treated males held with the GnRHa+Dom-treated females
      showed higher levels of plasma 11-KT than those held with GnRHa-treated females,
      indicating an additive effect which is probably attributable to female
      pheromones. Fully mature females were induced to spawn by injecting GnRHa alone
      or coupled with metaclopramide (a dopamine D2 receptors antagonist). The combined
      treatment, which included a dopamine antagonist, was found to be more potent in
      inducing ovulation and spawning as compared to GnRHa alone. In conclusion, our
      data suggest that dopaminergic inhibition is a major barrier along the
      reproductive axis that arrests spontaneous spawning in captive mullets.

PMID- 15862566
TI  - Determination of the expression pattern of the dual promoter of zebrafish fushi
      tarazu factor-1a following microinjections into zebrafish one cell stage embryos.
AB  - The zebrafish fushi tarazu factor-1a (ff1a) is a transcription factor belonging
      to the NR5A subgroup of nuclear receptors. The NR5A receptors bind DNA as
      monomers and are considered to be orphans due to their ability to promote
      transcription of downstream genes without ligands. In zebrafish, four ff1
      homologues (Ff1a, Ff1b, Ff1c, and Ff1d) have been identified so far. The gene
      coding for Ff1a is driven by two separate promoters, and give rise to four splice
      variants. Ff1a is expressed in the somites and pronephric ducts during
      somitogenesis and in the brain, liver, and mandibular arch during later embryonic
      stages. In adults the gene is highly expressed in gonads, liver, and intestine,
      but can be detected in most tissues. The broad variety of embryonic expression
      domains indicates several important developmental features. One of the mammalian
      fushi tarazu factor-1 genes, steroidogenic factor-1 (SF-1), is essential for the
      development of gonads and adrenals. SF-1 is together with Sox9, WT1, and GATA4 a
      positive transcriptional regulator of human anti-mullerian hormone (AMH) and
      thereby linked to the male sex-determining pathway. The zebrafish ff1a dual
      promoter contains several GATA binding sites and E-boxes, a site for DR4, XFD2,
      MyoD, Snail, HNF3, S8, and an HMG-box recognition site for Sox9. In a first
      attempt to dissect the ff1a promoter in vivo we have produced first generation
      transgenes in order to determine the correlation between the expression of the
      endogenous ff1a gene and the microinjected ff1a dual promoter coupled to the
      pEGFP reporter vector. Our results show that the microinjected constructs are
      expressed in the correct tissues.

PMID- 15862567
TI  - Involvement of phospholipase C and intracellular calcium signaling in the
      gonadotropin-releasing hormone regulation of prolactin release from lactotrophs
      of tilapia (Oreochromis mossambicus).
AB  - Gonadotropin-releasing hormone (GnRH) is a potent stimulator of prolactin (PRL)
      secretion in various vertebrates including the tilapia, Oreochromis mossambicus.
      The mechanism by which GnRH regulates lactotroph cell function is poorly
      understood. Using the advantageous characteristics of the teleost pituitary gland
      from which a nearly pure population of PRL cells can be isolated, we examined
      whether GnRH might stimulate PRL release through an increase in phospholipase C
      (PLC), inositol triphosphate (IP3), and intracellular calcium (Ca(i)2+)
      signaling. Using Ca(i)2+ imaging and the calcium-sensitive dye fura-2, we found
      that chicken GnRH-II (cGnRH-II) induced a rapid dose-dependent increase in
      Ca(i)2+ in dispersed tilapia lactotrophs. The Ca(i)2+ signal was abolished by U
      73122, an inhibitor of PLC-dependent phosphoinositide hydrolysis.
      Correspondingly, cGnRH-II-induced tPRL188 secretion was inhibited by U-73122,
      suggesting that activation of PLC mediates cGnRH-II's stimulatory effect on PRL
      secretion. Pretreatment with 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate
      hydrochloride (TMB-8), an inhibitor of Ca2+ release from intracellular stores,
      impeded the effect of cGnRH-II on Ca(i)2+. To further address the possible
      involvement of intracellular Ca2+ stores, IP3 concentrations in the tilapia
      rostral pars distalis (RPD containing 95-99% PRL cells) was determined by a
      radioreceptor assay. We found that GnRH-II induces a rapid (<5min) and sustained
      increase in IP3 concentration in the RPD. Secretion of tPRL(188) in response to
      cGnRH-II was suppressed by Ca2+ antagonists (TMB-8 and nifedipine). These data,
      along with our previous findings that show PRL release increases with a rise in
      Ca(i)2+, suggest that GnRH may elicit its PRL releasing effect by increasing
      Ca(i)2+. Furthermore, the rise in Ca(i)2+ may be derived from PLC/IP3-induced
      mobilization of Ca2+ from intracellular stores along with influx through L-type
      voltage-gated Ca2+ channels.

PMID- 15862568
TI  - Long-term treatment of ghrelin stimulates feeding, fat deposition, and alters the
      GH/IGF-I axis in the tilapia, Oreochromis mossambicus.
AB  - Recently, a new peptide, ghrelin, which specifically stimulates growth hormone
      (GH) release from the pituitary, was identified in the rat and human stomach.
      Ghrelin has been shown to stimulate GH release by acting through a growth hormone
      secretagogue receptor. We have identified two ghrelins (ghrelin-C8 and -C10) in
      the stomach of tilapia, a euryhaline fish. The current study was aimed at
      investigating the in vivo effect of the two tilapia ghrelins on feeding, fat
      deposition, and on the GH/IGF-I axis. Tilapia were implanted with micro-osmotic
      pumps containing either ghrelin-C8, ghrelin-C10 or saline (control). Ghrelin was
      delivered at a continuous rate of 10 ng/h for 21 days. Food consumption increased
      significantly in those animals that received ghrelin-C10 but not ghrelin-C8.
      Treatment with ghrelin-C10 increased body weight significantly without altering
      body length. Hence, the condition factor was significantly higher in the ghrelin
      C10 group compared with the control. Liver weight and total fat content in the
      liver were also elevated significantly in the fish treated with ghrelin-C10.
      There was no effect of either ghrelin on plasma GH levels, whereas plasma IGF-I
      levels were reduced significantly in the ghrelin-C10 group. These findings
      demonstrate that ghrelin plays a role in feeding and fat metabolism in the
      tilapia, and suggest that the two forms of ghrelin may be acting through
      different receptors.

PMID- 15862569
TI  - Effects of cadmium exposure on testis apoptosis in the marine teleost Gobius
      niger.
AB  - It is known that heavy metals can accumulate in tissues during aquatic organism
      growth (bioaccumulation) and often biomagnify up the food chain interfering with
      the health and reproduction of both wildlife and humans. Recently, cadmium (Cd)
      was included in the endocrine disruptors list, exerting its effect on gametes
      quality and reproductive functions; in addition, its role as apoptotic factor was
      evidenced in different cell types and tissues. In the present study, the effects
      of two different Cd doses on testis and liver of the black goby Gobius niger were
      analyzed. Cd concentration in the water and its uptake by the gills were measured
      by differential pulse anodic stripping voltammetry. Toxic, apoptotic, and
      stressor Cd effects were analyzed using metallothionein (MTT), caspase 3 and
      heath shock protein 70 (HSP70), respectively, as bioindicators. The results of
      the present study suggested that, in the gills, the saturation of all specific
      metal sites was reached only with the highest Cd dose exposure. Either testis and
      liver showed an increase of MTT gene expression and protein synthesis in addition
      to HSP70 gene expression, related with Cd concentration in the water indicating
      that both tissues were affected by Cd exposure. In conclusion, the present study,
      not only shows the toxic effect of Cd on hepatic tissue, but also indicates its
      potency as apoptotic factor in the testis. This is supported by the increase of
      caspase 3 gene expression and the presence of its active form in testis of
      exposed fish.

PMID- 15862570
TI  - Cortisol stimulates growth hormone gene expression in rainbow trout leucocytes in
      vitro.
AB  - Extrapituitary expression of the growth hormone (GH) gene has been reported for
      the immune system of various vertebrates. In the rainbow trout (Oncorhynchus
      mykiss), GH mRNA could be detected in several lymphoid organs and leucocytes by
      reverse transcriptase-polymerase chain reaction (RT-PCR). To understand the
      control of GH expression in the fish immune system, mRNA levels for two distinct
      GH genes (GH1 and GH2) in trout leucocytes isolated from peripheral blood were
      quantified using a real-time PCR method. Both GH mRNAs could be detected in trout
      leucocytes, although their levels were extremely low compared to those in
      pituitary cells. The levels of GH2 mRNA in leucocytes were several times higher
      than those of GH1, while no difference was observed between GH1 and GH2 mRNA
      levels in the pituitary. Administration of dibutyryl cyclic AMP and cortisol
      produced a significant elevation of GH mRNA levels in trout leucocytes, although
      the levels were unchanged by T3. GH1 and GH2 mRNA levels showed similarities in
      responses to those factors. The effect of cortisol on GH mRNA appears biphasic; a
      dose-depending elevation of GH gene expression was observed in leucocytes treated
      with cortisol at below 200 nM, however, cortisol had no effect at 2000 nM.
      Cortisol-treated leucocytes showed no significant change in the mRNA level of
      beta-actin or proliferative activity during the experiments. Our results thus
      show that, at the low levels, GH gene expression in trout leucocytes is regulated
      by cortisol, which has been known as a regulatory factor of GH gene expression in
      pituitary cells, and suggest a physiological significance of paracrine GH
      produced in the fish immune system.

PMID- 15862571
TI  - Effects of cortisol and stress on channel catfish (Ictalurus punctatus) pathogen
      susceptibility and lysozyme activity following exposure to Edwardsiella ictaluri.
AB  - Periods of stress are often associated with disease outbreaks in cultured fish,
      and stress is often characterized by the secretion of cortisol. Although stress
      and cortisol secretion are highly correlated in fish, the role of cortisol in
      affecting channel catfish (Ictalurus punctatus) pathogen susceptibility is
      unclear. The effects of short-term stress and exogenous cortisol administration
      on channel catfish susceptibility to Edwardsiella ictaluri, the etiologic agent
      of enteric septicemia of catfish (ESC), were investigated. Channel catfish were
      exposed to virulent E. ictaluri following a standardized 30-min low-water stress
      or administration of dietary cortisol (100 mg/kg feed) and compared to a pathogen
      challenged control group of catfish. Pathogen susceptibility increased in
      stressed catfish (43.3% mortality) when compared to cortisol-fed catfish (26.7%)
      and controls (26.7%). A greater (P<0.05) percentage of stressed catfish (25.9%)
      tested positive for E. ictaluri relative to cortisol-fed catfish (13.0%) over the
      course of the study, however, average levels of circulating bacteria were not
      different (P>0.05) among the treatments. Catfish challenged by the low-water
      stress event had elevated (P<0.05) circulating levels of cortisol 1-day post
      pathogen exposure and elevated (P<0.05) lysozyme activity 4 and 14 days post
      pathogen exposure when compared to cortisol-fed and control-challenged catfish.
      Cortisol concentrations were not correlated (P>0.05) to either lysozyme activity
      or bacterial levels; however, lysozyme activity was positively correlated
      (P=0.0197) to blood bacterial concentrations. These results implicate other
      stress factors or pathways, separate from or possibly in conjunction with
      cortisol, in the stress-associated immunosuppression of channel catfish as it
      relates to ESC susceptibility.

PMID- 15862572
TI  - Biolistic transformation of Schistosoma mansoni with 5' flanking regions of two
      peptidase genes promotes tissue-specific expression.
AB  - The gene-regulatory elements controlling peptidase expression in Schistosoma
      mansoni are unknown. A genomic DNA library was constructed from which 5' flanking
      fragments of the cathepsins F (SmCF; 649 bp) and B2 (SmCB2; 810 bp) peptidase
      genes were isolated. These were cloned into a GFP-expression vector for biolistic
      transformation of schistosomes. Both fragments promoted expression of GFP that
      was localised in the gut for SmCF and tegument for SmCB2, consistent with
      previous immunochemical data. Promoter-deletion of the SmCF gene indicated the
      importance of one or more transcription factor binding sites in the first 169 bp
      for both GFP-expression and its tissue specificity.

PMID- 15862573
TI  - Opisthorchis viverrini antigen induces the expression of Toll-like receptor 2 in
      macrophage RAW cell line.
AB  - Opisthorchis viverrini infection induces inflammation in and around the bile
      duct, leading to cholangiocarcinoma in humans. To examine the mechanism of O.
      viverrini-induced inflammatory response, we assessed the expression of Toll-like
      receptors (TLRs) in RAW 264.7 macrophage cell line treated with an extract of O.
      viverrini antigen. Flow cytometry and immunocytochemistry showed that O.
      viverrini antigen induced the expression of TLR2 but not TLR4. Western blotting
      and immunocytochemistry revealed that nuclear factor-kappaB (NF-kappaB),
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were
      expressed in RAW 264.7 cells treated with O. viverrini antigen in a dose
      dependent manner. These results suggest that O. viverrini induces inflammatory
      response through TLR2-mediated pathway leading to NF-kappaB-mediated expression
      of iNOS and COX-2.

PMID- 15862574
TI  - Insights into unique physiological features of neutral lipids in Apicomplexa:
      from storage to potential mediation in parasite metabolic activities.
AB  - The fast intracellular multiplication of apicomplexan parasites including
      Toxoplasma and Plasmodium, requires large amounts of lipids necessary for the
      membrane biogenesis of new progenies. Hence, the study of lipids is fundamental
      in order to understand the biology and pathogenesis of these deadly organisms.
      Much has been reported on the importance of polar lipids, e.g. phospholipids in
      Plasmodium. Comparatively, little attention has been paid to the metabolism of
      neutral lipids, including sterols, steryl esters and acylglycerols. In eukaryotic
      cells, free sterols are membrane components whereas steryl esters and
      acylglycerols are stored in cytosolic lipid inclusions. The first part of this
      review describes the recent advances in neutral lipid synthesis and storage in
      Toxoplasma and Plasmodium. New potential pharmacological targets in the pathways
      producing neutral lipids are outlined. In addition to lipid bodies, Apicomplexa
      contain unique secretory organelles involved in parasite invasion named
      rhoptries. These compartments appear to sequester most of the cholesterol found
      in the exocytic pathway. The second part of the review focuses on rhoptry
      cholesterol and its potential roles in the biogenesis, structural organisation
      and function of these unique organelles among eukaryotes.

PMID- 15862575
TI  - Annexin-like alpha giardins: a new cytoskeletal gene family in Giardia lamblia.
AB  - Through a genome survey and phylogenetic analysis, we have identified and
      sequenced 14 new coding regions for alpha-giardins in Giardia lamblia. These
      proteins are related to annexins and comprise a multi-gene family with 21
      members. Many alpha giardins are highly expressed proteins that are very
      immunogenic during acute giardiasis in humans. However, little is known about the
      function of these proteins. By using PCR with different combinations of gene
      specific primers, we demonstrated that several of the genes localised to the same
      chromosomal fragment. These data point towards a molecular evolution through gene
      duplication and subsequent functional divergence. Semi-quantitative reverse
      transcriptase-PCR analysis of the Giardia life cycle revealed large differences
      in mRNA expression levels of the alpha giardins. Epitope tagging of the alpha
      giardins localised them to different cytoskeletal components, such as the
      flagella and the adhesive disc, but also to the plasma membrane. These
      localisation experiments suggest alpha-giardins play a role in cell motility,
      attachment and membrane stability.

PMID- 15862576
TI  - Hsp90 is essential in the filarial nematode Brugia pahangi.
AB  - The development of a compound with activity against filarial nematodes (a
      'macrofilaricide') has been a long-standing goal of the World Health
      Organization. However, adult filariae have proved remarkably difficult to kill.
      To some extent this reflects a lack of understanding of key pathways and
      processes in filarial nematodes that may be suitable targets for chemotherapy. In
      this paper we show that geldanamycin (GA), a specific inhibitor of the activity
      of the heat shock protein 90 (Hsp90) family, kills adult worms and microfilariae
      (Mf) of Brugia pahangi at nanomolar concentrations. In addition, release of Mf
      from adult worms is inhibited within 24 h of exposure to GA and is not
      recoverable, demonstrating that GA effectively sterilises the worm. Similar
      results were obtained with a second filarial worm Acanthocheilonema viteae. In
      contrast GA has no effect on the free-living nematode Caenorhabditis elegans
      despite a high degree of conservation between the nematode Hsp90 sequences. In
      keeping with these findings, Brugia Hsp90 binds GA in a solid phase pull-down
      assay while the binding of C. elegans Hsp90 to immobilised GA is undetectable. In
      other eukaryotes, GA is known to bind in the N-terminal ATP pocket of Hsp90,
      disrupting its interactions with client proteins which are then targeted for
      degradation via the proteasome pathway. Thus, Hsp90 or some of its client
      proteins may provide novel targets for the chemotherapy of filarial infection.

PMID- 15862577
TI  - Differential effects of polyamine derivative compounds against Leishmania
      infantum promastigotes and axenic amastigotes.
AB  - The natural polyamines are ubiquitous polycationic compounds that play important
      biological functions in cell growth and differentiation. In the case of protozoan
      species that are causative agents of important human diseases such as
      Leishmaniasis, an exogenous supply of polyamines supports parasite proliferation.
      In the present study, we have investigated the effect of three polyamine
      derivatives, (namely bis-naphthalimidopropyl putrescine (BNIPPut), spermidine
      (BNIPSpd) and spermine (BNIPSpm)), on the proliferative stages of Leishmania
      infantum, the causative agent of visceral leishmaniasis in the Mediterranean
      basin. A significant reduction of promastigotes and axenic amastigotes growth was
      observed in the presence of increasing concentrations of the drugs, although the
      mechanisms leading to the parasite growth arrest seems to be different. Indeed,
      by using a number of biochemical approaches to analyse the alterations that
      occurred during early stages of parasite-drug interaction (i.e. membrane
      phosphatidylserine exposure measured by annexin V binding, DNA fragmentation,
      deoxynucleotidyltranferase-mediated dUTP end labelin (TUNEL), mitochondrial
      transmembrane potential loss), we showed that the drugs had the capacity to
      induce the death of promastigotes by a mechanism that shares many features with
      metazoan apoptosis. Surprisingly, the amastigotes did not behave in a similar way
      to promastigotes. The drug inhibitory effect on amastigotes growth and the
      absence of propidium iodide labelling may suggest that the compounds are acting
      as cytostatic substances. Although, the mechanisms of action of these compounds
      have yet to be elucidated, the above data show for the first time that polyamine
      derivatives may act differentially on the Leishmania parasite stages. Further
      chemical modifications are needed to make the polyamine derivatives as well as
      other analogues able to target the amastigote stage of the parasite.

PMID- 15862578
TI  - Patterns of host specificity and transmission among parasites of wild primates.
AB  - Multihost parasites have been implicated in the emergence of new diseases in
      humans and wildlife, yet little is known about factors that influence the host
      range of parasites in natural populations. We used a comprehensive data set of
      415 micro- and macroparasites reported from 119 wild primate hosts to investigate
      broad patterns of host specificity. The majority (68%) of primate parasites were
      reported to infect multiple host species, including animals from multiple
      families or orders. This pattern corresponds to previous studies of parasites
      found in humans and domesticated animals. Within three parasite groups (viruses,
      protozoans and helminths), we examined parasite taxonomy and transmission
      strategy in relation to measures of host specificity. Relative to other parasite
      groups, helminths were associated with the greatest levels of host specificity,
      whereas most viruses were reported to infect hosts from multiple families or
      orders. Highly significant associations between the degree of host specificity
      and transmission strategy arose within each parasite group, but not always in the
      same direction, suggesting that unique constraints influence the host range of
      parasites within each taxonomic group. Finally characteristics of over 100
      parasite species shared between wild primates and humans, including those
      recognised as emerging in humans, revealed that most of these shared parasites
      were reported from multiple host orders. Furthermore, nearly all viruses that
      were reported to infect both humans and non-human primates were classified as
      emerging in humans.

PMID- 15862579
TI  - Redescription of Besnoitia bennetti (Protozoa: Apicomplexa) from the donkey
      (Equus asinus).
AB  - Besnoitia bennetti tissue cysts were found in four naturally-infected donkeys
      (Equus asinus) from the USA. Infectivity of its bradyzoites and tachyzoites to
      animals and cell culture was studied. The bradyzoites were not infectious to out
      bred Swiss Webster mice, rabbits or gerbils. When fed tissue cysts, cats did not
      excrete oocysts. However, the parasite was infectious to interferon-gamma gene
      knock out mice. The parasite from tissues of two donkeys was grown successfully
      in bovine monocyte monolayers for the first time. Non-dividing, uninucleate
      tachyzoites were approximately 6 x 1.5 microm in size. Longitudinally-cut
      bradyzoites in tissue sections measured 8.7 x 1.9 microm. Ultrastructurally,
      tachyzoites and bradyzoites were similar to those in other Besnoitia species, and
      in particular to parasites described from cattle (Besnoitia besnoiti) and
      reindeer (Besnoitia tarandi), in that their bradyzoites lacked enigmatic bodies.
      Based on comparative analysis of three portions of nuclear ribosomal DNA (the
      small and large subunits and the first internal transcribed spacer) B. bennetti
      was found to be more closely related to the other congeners described from
      ungulates. The parasite was formally redescribed and specimens deposited in the
      US National Parasite Collections.

PMID- 15862580
TI  - Clams (Corbicula fluminea) as bioindicators of fecal contamination with
      Cryptosporidium and Giardia spp. in freshwater ecosystems in California.
AB  - This study evaluated clams as bioindicators of fecal protozoan contamination
      using three approaches: (i) clam tissue spiking experiments to compare several
      detection techniques; (ii) clam tank exposure experiments to evaluate clams that
      had filtered Cryptosporidium oocysts from inoculated water under a range of
      simulated environmental conditions; (iii) sentinel clam outplanting to assess the
      distribution and magnitude of fecal contamination in three riverine systems in
      California. Our spiking and tank experiments showed that direct fluorescent
      antibody (DFA), immunomagnetic separation (IMS) in combination with DFA, and PCR
      techniques could be used to detect Cryptosporidium in clam tissues. The most
      analytically sensitive technique was IMS concentration with DFA detection of
      oocysts in clam digestive gland tissues, which detected 10 oocysts spiked into a
      clam digestive gland 83% of the time. In the tank experiment, oocyst dose and
      clam collection time were significant predictors for detecting Cryptosporidium
      parvum oocysts in clams. In the wild clam study, Cryptosporidium and Giardia were
      detected in clams from all three study regions by IMS-DFA analysis of clam
      digestive glands, with significant variation by sampling year and season. The
      presence of C. parvum DNA in clams from riverine ecosystems was confirmed with
      PCR and DNA sequence analysis.

PMID- 15862581
TI  - Developmental expression and molecular analysis of two Meloidogyne incognita
      pectate lyase genes.
AB  - Proteinaceous secretions from the oesophageal glands of plant-parasitic nematodes
      have crucial roles in nematode parasitism of plants. Two cDNAs (designated Mi-pel
      1 and Mi-pel-2) encoding pectate lyases were isolated from the root-knot
      nematode, Meloidogyne incognita, oesophageal gland-cell subtractive cDNA
      libraries, and the corresponding genomic DNAs were subsequently cloned. Southern
      blot analyses revealed that homologues to these pectate lyase genes were broadly
      distributed in Meloidogyne species, and present as members of a small multigene
      family. Mi-pel-1 and Mi-pel-2 encoded, respectively, predicted proteins of 271
      and 280 amino acids, each of which was preceded by a signal peptide for
      secretion. Interestingly, these pectate lyases showed diversity at the amino acid
      level, with only 31% identity and 49% similarity. These pectate lyases were
      classified into the same family of pectate lyases with those of other
      phytoparasitic nematodes that contain four conserved regions characteristic of
      the class III pectate lyases of microbes. In situ mRNA hybridisation analyses
      showed the transcripts of Mi-pel-1 and Mi-pel-2 accumulated exclusively within
      the subventral oesophageal gland cells of M. incognita. RT-PCR analysis confirmed
      that their transcriptions were strong at the pre-parasitic and early parasitic
      second-stage juveniles, and not detectable at the late parasitic stages of the
      nematodes. These results indicated that these pectate lyases, like cellulases,
      could be secreted into plant tissues to facilitate the penetration and
      intercellular migration of M. incognita during the early stages of plant
      parasitism.

PMID- 15862582
TI  - Echinococcus shiquicus n. sp., a taeniid cestode from Tibetan fox and plateau
      pika in China.
AB  - The taeniid cestode Echinococcus shiquicus n. sp. was found from the Tibetan fox
      Vulpes ferrilata and the plateau pika Ochotona curzoniae in the Qinghai-Tibet
      plateau region of China. In the adult stage, E. shiquicus from the foxes is
      morphologically similar to Echinococcus multilocularis. However, the new species
      is differentiated by its smaller rostellar hooks, fewer segments, distinct
      position of genital pore in the mature segment and fewer eggs in the gravid
      segment. Hydatid cysts of E. shiquicus found in the livers from the pikas were
      essentially unilocular but an oligovesicular cyst was also found. The data of
      mitochondrial and nuclear DNA sequences proved E. shiquicus to be a valid taxon.

PMID- 15862583
TI  - Alterations of hepatic microsomal enzymes in the early phase of murine
      schistosomiasis.
AB  - Schistosoma mansoni has been reported to cause a downregulation of hepatic
      cytochrome P450 activities after granulomas are formed around worm eggs harbored
      in the mouse liver. Only a few studies, however, provided data on the activity of
      xenobiotic-biotransaformation enzymes in the early phase of S. mansoni infection.
      In this study, we evaluated the alterations of liver microsomal enzymes during
      early infection (post-infection days, PIDs, 15 and 30) when granulomas are not
      found in the mouse liver yet. Swiss Webster (SW) and DBA/2 mice of either sex
      were infected with 100 S. mansoni cercariae on postnatal day 10. Levels of total
      CYPs and activities of alkoxyresorufin-O-dealkylases (EROD, MROD, PROD and BROD),
      N-nitrosodimethylamine-N-demethylase (NDMA-d), coumarin 7-hydroxylase (COH, DBA/2
      only) and UDP-glucuronosyltransferase (UGT) were measured in liver microsomes
      from mice killed on PIDs 15 and 30. Age-matched (sham-infected) mice of the same
      sex and strain were used as controls. Neither total-CYP levels nor microsomal
      enzyme activities were altered in SW and DBA/2 mice on PID 15. On PID 30, total
      CYP levels, and COH, PROD and UGT activities remained unaltered, while gender-
      and strain-specific minor changes of EROD, MROD, BROD and NDMA-d (i.e., increase
      in SW and reduction in DBA/2) were found. In conclusion, our results suggest
      that, contrasting to a consistent and almost generalized downregulation of CYPs
      in chronic schistosomiasis, alterations of hepatic CYPs in early (acute)
      infection are isoform and mouse's gender and strain specific.

PMID- 15862584
TI  - Genetic diversity of merozoite surface protein-1 gene of Plasmodium vivax
      isolates in mining villages of Venezuela (Bolivar State).
AB  - The merozoite surface protein-1 gene of Plasmodium vivax is highly polymorphic
      and so, currently used in epidemiological studies of P. vivax malaria. We
      sequenced the variable block 5 of the gene from 39 Venezuelan isolates, 18 of
      which were co-infected with Plasmodium falciparum. We observed a limited
      variability with 34 isolates belonging to the type Salvador I, none Belem type
      and only five recombinants. Among the recombinants, only two types of sequences
      were observed with, respectively, 18 and 21 poly-Q residues. Nucleotide
      substitutions explained the major differences of the 11 patterns observed. We
      could evidence neither specific MSP-1 genotype associated with co-infected
      samples, nor peculiar MSP-1 genotype distribution inside the investigated areas.
      In comparison with other low endemic regions in the world, our sampling has a
      lower genetic diversity, which could be mainly explained by the lack of Belem
      type. In fact, the variable repeats of poly-Q residues involved in the
      polymorphism of Belem type and recombinant isolates are responsible for a great
      part of variability observed in MSP-1 block 5.

PMID- 15862585
TI  - The reinfection threshold does not exist.

PMID- 15862586
TI  - Behavior pattern (innate action) of individuals in fish schools generating
      efficient collective evasion from predation.
AB  - The schooling of fishes is one typical animal social behavior. One primary
      function of fish school is to protect members when attacked by predators. One
      main way that the school reduces the predator's chance of making a successful
      kill is to confuse the predator as it makes its strike. This may be accomplished
      by collective evasion behaviors organized through integration of motions of
      individual fish made based on their innate actions (behavior patterns). In order
      to investigate what kind of behavior pattern of individuals can generate the
      efficient collective evasion of a school, we present a model of evasion behavior
      pattern which consists of three component behavior patterns, schooling,
      cooperative escape, and selfish escape behavior patterns and the rule for choice
      of one among them with proper timing. Each fish determines its movement direction
      taking into account simultaneously three kinds of elemental motions, mimicking
      its neighbors, avoiding collisions with its nearest neighbors, and escaping from
      an approaching predator. The weights of three elemental motions are changed
      depending on which component behavior pattern the fish carries out. The values of
      the weights for three component behavior patterns can be definitively determined
      under the condition that the collective evasion of the school becomes the most
      efficient, that is, the probability that any member is eaten by the predator
      becomes minimum.

PMID- 15862587
TI  - HIV may produce inhibitory microRNAs (miRNAs) that block production of CD28, CD4
      and some interleukins.
AB  - It is well-known that HIV-1 infection results in a gradual decline of the CD4+ T
      lymphocytes, but the underlying mechanism of this decline is not completely
      understood. Research has shown that HIV-1 infection of CD4+ T cells results in
      decreased CD28 expression, but the mechanism of this repression is unknown. There
      is also substantial evidence demonstrating regulatory involvement of microRNA
      (miRNA) during protein expression in plants and some animals, and reports have
      recently been published confirming the existence of viral-encoded miRNAs. Based
      on these findings, we hypothesize that viral-encoded miRNA from HIV-1 may
      directly alter T cell, macrophage and dendritic cell activity. To investigate a
      potential correlation between the genomic complementarity of HIV-1 and host cell
      protein expression, a local alignment search was performed to assess for regions
      of complementarity between the HIV-1 proviral genome and the mRNA coding sequence
      of various proteins expressed by CD+ T cells and macrophages. Regions of
      complementarity with strong correlations to the currently established criteria
      for miRNA:target mRNA activity were found between HIV-1 and CD28, CTLA-4 and some
      interleukins, suggesting that HIV-1 may produce translational repression in host
      cells.

PMID- 15862588
TI  - A kinetic mechanism for Drosophila bicoid cooperative binding.
AB  - The Bicoid (Bcd) protein is a concentration-dependent transcriptional activator
      in the embryo of Drosophila melanogaster. Bcd regulates the expression of the
      maternal and zygotic gene hunchback (hb) that shows a step-like-function
      expression pattern, in the anterior half of the egg. The regulatory region of hb
      contains six major binding sites for the Bcd protein, named A1, A2, A3 (strong
      sites), and X1, X2, X3 (weak sites). Cooperativity between Bcd molecules binding
      to the hb enhancer element has been characterized as an important mechanism for
      the step-like shape of hb anterior expression domain. The objective of the
      present report is to analyse the mechanism of this cooperative binding based on a
      reaction network model. Using this method we have analysed experimental results
      from the literature describing how the Bcd protein binds to hb enhancer elements
      containing the A1 or X1 site alone or these two sites together at wild type
      distance. This approach allows us to estimate the kinetic constants of protein
      protein and protein-DNA interactions. Moreover our results suggest that binding
      of a Bcd dimer to the hb enhancer element is more stable than binding of a
      monomer. We propose a cooperative kinetic mechanism for binding of Bcd to the hb
      enhancer element: First, a monomer binds to the site with a relatively low
      affinity; after that, another monomer binds to the first one with higher
      affinity, generating a dimer bound to the site. This yet unreported monomer
      monomer cooperative mechanism takes place for occupancy of either one-site or two
      site enhancer elements. In addition, we find cooperativity between neighbor
      sites, as previously reported in the literature.

PMID- 15862589
TI  - Chemical constraints on the evolution of olfactory communication channels of
      moths.
AB  - It is estimated there are over 100,000 moth species (Lepidoptera) that produce
      sex pheromones comprising communication channels used in specific-mate
      recognition systems (SMRS) involved in pre-zygotic mating isolation and
      speciation. About 1572 moth species have been found to use 377 pheromone
      components, the majority being alcohols, aldehydes or acetate esters of olefinic
      chains of 10-22 carbons. Since there are limited numbers of possible unsaturated
      (double bonded) E- and Z-configured isomers of these chains, there may be
      constraints on incipient species evolving new pheromone components, especially if
      they are utilized by existing species. Here I develop algorithms that count and
      name all possible structures of chains with or without a functional group. The
      results show that for acetate esters there are only seven or nine monounsaturated
      isomers of six or seven carbon chains, respectively, suggesting use of these
      compounds could limit the number of communication channels available for
      radiation of new species (no moths use these short chains). For commonly used 14
      carbon chains with an acetate ester functional group, and 1-3 unsaturations,
      there are 1039 isomers. A total of 2,096,883 isomers were counted from all
      multiply unsaturated 10-22-carbon chain acetate esters. The number of possible
      signals quickly extends into millions when considering pheromone blends of 2-4
      components used by most species. There should be little chemical constraint on
      evolution of new communication channels based on compounds of 10 or more carbons,
      even for closely related species (e.g. ermine moths, Yponomeuta).

PMID- 15862590
TI  - Background selection and population differentiation.
AB  - A general analytical formula is derived, which predicts the effects of background
      selection on population differentiation at a neutral locus as a result of its
      linkage with selected loci of deleterious mutations. The theory is based on the
      assumptions of random mating, multiplicative fitness, and weak selection in
      hermaphrodite plants in the island model of population structure. The analytical
      results show that Fst at the neutral locus increases as a result of the effects
      of background selection, regardless of the dependence or independence among
      linked background selective loci. The increment in Fst is closely related to the
      magnitude of linkage disequilibria between the neutral locus and selected loci,
      and can be estimated by the ratio of Fst with background selection to Fst without
      background selection minus one. The steady-state linkage disequilibrium between a
      neutral locus and a selected locus in subpopulations, primarily attained by gene
      flow, decreases with the recombination rate, and can be enhanced when there are
      dependence among linked selected loci. Monte Carlo computer simulations with two-
      and three-locus models show that the analytical formulae perform well under
      general conditions. Application of the present theory may aid in analyzing the
      genome-wide mapping of the effect of background selection in terms of Fst.

PMID- 15862591
TI  - Chemotaxis and random motility in unsteady chemoattractant fields: a
      computational study.
AB  - We discuss a generic computational model which captures the effects of transient
      chemoattractant concentration on the chemotactic motility of individual cells.
      The model solves the appropriate unsteady chemoattractant transport equation
      using finite differences, while simultaneously executing biased random walks
      representing individual cells. The simulations were implemented for a 2D
      homogeneous domain, and two case studies were considered. In the first case
      study, we consider a single-point source at the origin of the domain which
      produces chemoattractant, while other cells execute biased random walks toward
      this point source. We observe that for continuous chemoattractant production,
      chemoattractant diffusivity has no effect on cell motility, as measured by the
      mean of time to reach the source. However, in the case of pulsed random
      production with a specific average duty cycle, the mean time-to-contact is
      generally minimal with respect to chemoattractant diffusivity over a moderate
      range of diffusivities. In the second case study, two mobile cells which
      simultaneously secrete chemoattractant are initially placed a certain distance
      apart and are then allowed to execute biased random walks. Our model shows that a
      pulsed random protocol for chemoattractant production facilitates the two cells
      "finding" one another compared to continuous production. From this case study we
      also learn that there exists a range of moderate chemoattractant diffusivities
      for which the mean time-to-contact is minimal when cells both produce/detect
      chemoattractant and chemotactically migrate. Using these case studies, we discuss
      how transience in chemoattractant concentration becomes important in
      characterizing the effectiveness of chemotaxis.

PMID- 15862592
TI  - Altruism may arise from individual selection.
AB  - The fact that humans cooperate with non-kin in large groups, or with people they
      will never meet again, is a long-standing evolutionary puzzle. Altruism, the
      capacity to perform costly acts that confer benefits on others, is at the core of
      cooperative behavior. Behavioral experiments show that humans have a
      predisposition to cooperate with others and to punish non-cooperators at personal
      cost (so-called strong reciprocity) which, according to standard evolutionary
      game theory arguments, cannot arise from selection acting on individuals. This
      has led to the suggestion of group and cultural selection as the only mechanisms
      that can explain the evolutionary origin of human altruism. We introduce an agent
      based model inspired on the Ultimatum Game, that allows us to go beyond the
      limitations of standard evolutionary game theory and show that individual
      selection can indeed give rise to strong reciprocity. Our results are consistent
      with the existence of neural correlates of fairness and in good agreement with
      observations on humans and monkeys.

PMID- 15862593
TI  - Evaluation of the performance of mechanisms for noise attenuation in a single
      gene expression.
AB  - Experiments of synthetic gene regulatory modules and theoretical studies have
      clarified the stochastic nature of gene expression. The establishment of methods
      to control the fluctuation in gene expression is an indispensable step to the
      synthesis of robust and reliable genetic modules. In this study, we evaluate the
      performances of several major mechanisms to attenuate the fluctuation in a single
      gene expression; noise attenuation through the control of the ratio of the
      transcription rate to the translation one, the interaction between synthesized
      proteins and background molecules, and an autoregulatory negative feedback. We
      analytically derive the dependence of the noise intensity on the parameter values
      related to elementary reaction processes, optimal conditions to attenuate the
      noise, and the limitation of the attenuation for those mechanisms. Our results
      can be an important basis for selecting the most efficient combination of the
      components in the design and synthesis of robust and reliable genetic modules.
      Furthermore, the knowledge on the performances that we obtain can also play a
      role in understanding the design principle of the intracellular gene regulatory
      networks.

PMID- 15862594
TI  - Bidirectional cytoplasmic incompatibility and the stable coexistence of two
      Wolbachia strains in parapatric host populations.
AB  - Wolbachiaare intracellular bacteria which are very widely distributed among
      arthropods. In many insect species Wolbachiaare known to induce cytoplasmic
      mating incompatibility (CI). It has been suggested that Wolbachiacould promote
      speciation in their hosts if parapatric host populations are infected with two
      different Wolbachiastrains causing bidirectional mating incompatibilities. A
      necessary condition for this speciation scenario to work is that the two
      Wolbachiastrains can stably coexist. The following study investigates this
      problem analysing a mathematical model with two host populations and migration
      between them. We show that the stability of bidirectional CI can be fully
      described in terms of a critical migration rate which is defined as the highest
      migration below which a stable coexistence of two Wolbachiastrains is possible.
      For some special cases we could derive analytical solutions for the critical
      migration rate; for the general case estimations of the critical migration rate
      are given. Our main finding is that bidirectional CI can stably persist in the
      face of high migration and can be as high as over 15% per generation for CI
      levels observed in nature. These results have implications for the potential of
      Wolbachiato promote genetic divergence and speciation in their hosts.

PMID- 15862595
TI  - Dynamical patterns of epidemic outbreaks in complex heterogeneous networks.
AB  - We present a thorough inspection of the dynamical behavior of epidemic phenomena
      in populations with complex and heterogeneous connectivity patterns. We show that
      the growth of the epidemic prevalence is virtually instantaneous in all networks
      characterized by diverging degree fluctuations, independently of the structure of
      the connectivity correlation functions characterizing the population network. By
      means of analytical and numerical results, we show that the outbreak time
      evolution follows a precise hierarchical dynamics. Once reached the most highly
      connected hubs, the infection pervades the network in a progressive cascade
      across smaller degree classes. Finally, we show the influence of the initial
      conditions and the relevance of statistical results in single case studies
      concerning heterogeneous networks. The emerging theoretical framework appears of
      general interest in view of the recently observed abundance of natural networks
      with complex topological features and might provide useful insights for the
      development of adaptive strategies aimed at epidemic containment.

PMID- 15862596
TI  - Architectural mutation and leaf form, for the palmate series.
AB  - Palmate leaf form occurs in both the ferns and angiosperms. The palmate leaf
      form, and its variants, is present in distantly separated clades within both
      ferns and angiosperms. There tend not to be intermediate forms which link these
      palmate leaves to other leaf forms within the taxonomic groups in question. The
      recurrence of homoplasious leaf forms in separate taxonomic groups could be a
      consequence of the algorithmic like mode of leaf growth. Leaves develop through
      the reiteration of modular units. It is probable that the homoplasious leaf forms
      in different taxa are derived independently through re-combinations of the
      parameters in the basic leaf form development algorithm.

PMID- 15862597
TI  - The effect of chronic calcium treatment on thyroid C cells in ovariectomized
      rats.
AB  - The purpose of this study was to investigate the influence of chronic calcium
      treatment on the structure and function of thyroid C cells in ovariectomzed adult
      female rats. Eighteen 3-month-old, female Wistar rats were divided into three
      groups. The first group was used as the sham-operated control, and the other two
      were surgically ovariectomized (Ovx). One month after gonadectomy, one group of
      Ovx rats was injected with 28.55 mg Ca-glucoheptonate (Ca)/kg b.w., while the
      other two groups were chronically treated with vehicle alone (Ovx and sham
      control). Two months after surgery, the animals were killed. In the thyroid C
      cells, calcitonin (CT) was localized with the peroxidase-antiperoxidase method.
      Stereology was used to evaluate morphometric changes in the volume of C cells,
      their nuclei and relative volume density. The number of C cells per unit area was
      calculated. Serum CT content was determined by radioimmunoassay. After chronic Ca
      treatment C cells were numerous with darker cytoplasm than in C cells of sham
      operated control animals, but more degranulated than the corresponding cells of
      Ovx rats. Their volume was significantly decreased by 14% (p < 0.05), while the
      number was increased by 47% (p < 0.05) in comparison with corresponding controls.
      Serum CT concentration was decreased by 27% (n.s.) in comparison to sham-operated
      control. Calcium treatment of Ovx rats led to a 32% increase of serum CT
      concentration in relation to untreated Ovx animals. These results suggest that
      chronic Ca treatment of Ovx female rats positively affected CT release from
      thyroid C cells, without any significant changes in morphometric parameters.

PMID- 15862598
TI  - Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on
      ethanol drinking.
AB  - Dopamine (DA) signals are transmitted via specific receptors including the D2
      receptors (D2R). Previous studies have shown that D2R upregulation in the nucleus
      accumbens (NAc) attenuated alcohol consumption. We hypothesized that upregulation
      of D2R in the NAc would significantly influence alcohol drinking. We tested this
      hypothesis by determining the effect that D2R upregulation has on alcohol intake
      in genetically altered mice lacking D2Rs. After a steady baseline of drinking
      behavior was established for all mice, a null vector or a genetically modified
      adenoviral vector containing the rat D2R cDNA was infused into the NAc of wild
      type (Drd2+/+), heterozygous (Drd2+/-), and receptor-deficient mice (Drd2-/-).
      Ethanol intake and preference were then determined using the two-bottle choice
      paradigm. Our results indicated that Drd2+/+ mice treated with the D2R vector
      significantly attenuated (58 %) their ethanol intake as well as reduced
      preference. Drd2+/- and mutant mice showed a similar attenuation, although the
      change was not as marked (12 %) and did not last as long. In contrast, Drd2-/-
      mice treated with the D2R vector displayed a temporary but significant increase
      (46 %) in ethanol intake and preference (consumption). These results supported
      the notion that the D2R plays an important role in alcohol consumption in mice
      and suggest that a key threshold range of D2R levels is associated with elevated
      alcohol consumption. Significant deviations in D2R levels from this range could
      impact alcohol consumption, and could help to explain possible individual
      variations in alcohol response, metabolism, sensitivity and consumption.

PMID- 15862599
TI  - Protective effects of Ginkgo biloba leaf extract on aluminum-induced brain
      dysfunction in rats.
AB  - This study examined the protective effects of Ginkgo biloba extract (GbE) on the
      learning and memory function in aluminum-treated rats and potential mechanisms.
      Wistar rats were given daily aluminum chloride 500 mg/kg, i.g, for one month,
      followed by continuous exposure via the drinking water containing 1600 ppm
      aluminum chloride for up to 5 months. The ability of spatial learning and memory
      was tested by Morris water maze. Aluminum administration significantly increased
      escape latency and searching distance, indicative of brain dysfunction. GbE
      treatment (50-200 mg/kg, i.g) significantly protected against aluminum-induced
      brain dysfunction, as evidenced by decreased escape latency and searching
      distance compared with the Al alone group. To examine the mechanisms of the
      protection, the expressions of amyloid precursor protein (APP) and caspase-3 in
      brain regions were examined by immunohistochemistry. GbE treatment reduced the
      contents of APP and caspase-3 in hippocampus of aluminum-treated rats in a dose
      dependent manner. At the highest dose of GbE (200 mg/kg), the immunostain for APP
      and caspase-3 was returned to normal levels. In summary, this study demonstrates
      that GbE is effective in improving the ability of spatial learning and memory of
      aluminum-intoxicated rats. This protection appears to be due to a decreased
      expression of APP and caspase-3 in rat brain, resulting in a decrease in the
      production of insoluble fragments of Abeta-amyloid.

PMID- 15862600
TI  - Effect of diabetic duration on serum concentrations of endogenous inhibitor of
      nitric oxide synthase in patients and rats with diabetes.
AB  - This study was designed to investigate the effect of diabetic duration on serum
      concentrations of endogenous inhibitor of nitric oxide synthase N(G), N(G)
      asymmetric dimethylarginine (ADMA) in patients and rats with diabetes, and to
      determine whether elevated endogenous ADMA is implicated in endothelial
      dysfunction or macroangiopathy in diabetes. Experimental diabetic model was
      induced by a single intraperitoneal injection of streptozotocin to male Sprague
      Dawley rats and fed for 2-, 4- and 8-week, respectively. Type 2 diabetic patients
      with different diabetic duration were recruited from Xiangya Hospital. Plasma
      glucose and serum ADMA levels were measured in both patients and rats. Moreover,
      endothelium-dependent relaxation of thoracic aortas and some parameters of
      metabolic control were examined in rats. Serum ADMA concentrations were
      significantly elevated in type 2 diabetic patients compared with healthy subjects
      (3.44 +/- 0.40 vs 1.08 +/- 0.14 micromol/L, n = 50 in diabetic patients and n =
      40 in healthy subjects, P < 0.01). The serum levels of ADMA in patients with
      macroangiopathy were higher than the patients without macroangiopathy (P < 0.01).
      But no difference was observed in serum ADMA concentrations between groups of
      patients with different diabetic duration. Similarly, serum levels of ADMA in
      diabetic rats were also significantly elevated at 2-week duration compared with
      duration-matched control (3.71 +/- 0.20 vs 1.04 +/- 0.23 micromol/L, n = 5
      approximately 6, P < 0.01). This elevation of ADMA was retained to 4- and 8-week
      (3.54 +/- 0.76 vs 0.95 +/- 0.06 micromol/L for 4-week, 3.21 +/- 0.50 vs 1.03 +/-
      0. 09 micromol/L for 8-week, n = 5 approximately 6, all P < 0.01) and remained
      unchanged among three diabetic groups. The elevation of ADMA was accompanied by
      impairment of endothelium-dependent relaxation and poor metabolic control in
      diabetic rat. These results first reveal that the extent of elevation in serum
      ADMA in both rats and patients with diabetes is not proportion with the length of
      their diabetic duration but rather with the metabolic control of this disease.
      Elevated endogenous ADMA may be implicated in diabetes-induced endothelial
      dysfunction and macroangiopathy. This study is helpful to prevention and
      treatment of diabetic-induced endothelial dysfunction or macroangiopathy.

PMID- 15862601
TI  - Involvement of death receptor signaling in mechanical stretch-induced
      cardiomyocyte apoptosis.
AB  - Recent evidences suggest that mechanical overload associated with abnormal blood
      pressure causes apoptosis in cardiovascular system. Still, the intracellular
      signaling leading to cardiomyocyte apoptosis has not been fully defined. Previous
      reports ascribed stretch-induced cardiomyocyte apoptosis to rennin-angiotensin
      system (RAS) signaling and/or mitochondria-dependent apoptosis pathway. The
      present study shows the involvement of death receptor signaling in mechanical
      stretch-induced cardiomyocyte apoptosis. By employing a well-described in vitro
      stretch model, we studied stretch-induced apoptosis and found that the death
      receptor-mediated apoptotic signaling was activated in stretch-induced apoptosis
      in neonatal rat cardiomyocytes. The major finding are as following: (1) The
      mechanical stretch activated death receptor-mediated apoptotic signaling in
      cardiomyocytes, including activation of caspases 8, 9 and 3, up-regulation of
      Fas, FasL expression and cell surface trafficking of death ligands (FasL and
      TRAIL); (2) That exogenous death ligand (TRAIL) enhanced, while soluble death
      receptor (sDR5) neutralized, stretch-induced apoptosis; (3) Adenovirus-delivered
      dominant negative FADD (FADD-DN) significantly reduced apoptosis, caspases 8, 9,
      and 3 activation, and stretch-induced cyt c release from mitochondria. These data
      clearly suggested mechanical stretch activated death receptor-mediated apoptotic
      signaling in cardiomyocytes. In conclusion, our data suggest that the FADD-linked
      death receptor signaling may contribute to stretch-induced cardiomyocyte
      apoptosis, probably through activating mitochondria-dependent apoptotic
      signaling.

PMID- 15862602
TI  - N-acetylcysteine inhibits hypoxic pulmonary hypertension most effectively in the
      initial phase of chronic hypoxia.
AB  - Exposure to chronic hypoxia results in hypoxic pulmonary hypertension (HPH). In
      rats HPH develops during the first two weeks of exposure to hypoxia, then it
      stabilizes and does not increase in severity. We hypothesize that free radical
      injury to pulmonary vascular wall is an important mechanism in the early days of
      the hypoxic exposure. Thus antioxidant treatment just before and at the beginning
      of hypoxia should be more effective in reducing HPH than antioxidant therapy of
      developed pulmonary hypertension. We studied adult male rats exposed for 4 weeks
      to isobaric hypoxia (F(iO2) = 0.1) and treated with the antioxidant, N
      acetylcysteine (NAC, 20 g/l in drinking water). NAC was given "early" (7 days
      before and the first 7 days of hypoxia) or "late" (last two weeks of hypoxic
      exposure). These experimental groups were compared with normoxic controls and
      untreated hypoxic rats (3-4 weeks hypoxia). All animals kept in hypoxia had
      significantly higher mean pulmonary arterial blood pressure (PAP) than normoxic
      animals. PAP was significantly lower in hypoxic animals with early (27.1 +/- 0.9
      mmHg) than late NAC treatment (30.5 +/- 1.0 mmHg, P < 0.05; hypoxic without NAC
      32.6 +/- 1.2 mmHg, normoxic controls 14.9 +/- 0.7 mmHg). Early but not late NAC
      treatment inhibited hypoxia-induced increase in right ventricle weight and
      muscularization of distal pulmonary arteries assessed by quantitative histology.
      We conclude that release of free oxygen radicals in early phases of exposure to
      hypoxia induces injury to pulmonary vessels that contributes to their structural
      remodeling and development of HPH.

PMID- 15862603
TI  - Oxidative stress in heroin administered mice and natural antioxidants protection.
AB  - The oxidative stress of heroin administered mice via intraperitoneal injection,
      and the therapeutic effects of exogenous antioxidants on the restrain of the
      oxidative damage of biomolecules and withdrawal syndrome were studied. After
      administered with heroin, mice showed decrease of total antioxidant capacity in
      blood, increase of reactive oxygen species production in white blood cells, and
      increase of oxidative damages of protein and lipid in brain and liver, but not in
      heart. On the other hand, exogenous antioxidants could restrain the oxidative
      stress, even alleviate withdrawal syndrome.

PMID- 15862604
TI  - Anti-obese action of raspberry ketone.
AB  - Raspberry ketone (4-(4-hydroxyphenyl) butan-2-one; RK) is a major aromatic
      compound of red raspberry (Rubus idaeus). The structure of RK is similar to the
      structures of capsaicin and synephrine, compounds known to exert anti-obese
      actions and alter the lipid metabolism. The present study was performed to
      clarify whether RK helps prevent obesity and activate lipid metabolism in
      rodents. To test the effect on obesity, our group designed the following in vivo
      experiments: 1) mice were fed a high-fat diet including 0.5, 1, or 2% of RK for
      10 weeks; 2) mice were given a high-fat diet for 6 weeks and subsequently fed the
      same high-fat diet containing 1% RK for the next 5 weeks. RK prevented the high
      fat-diet-induced elevations in body weight and the weights of the liver and
      visceral adipose tissues (epididymal, retroperitoneal, and mesenteric). RK also
      decreased these weights and hepatic triacylglycerol content after they had been
      increased by a high-fat diet. RK significantly increased norepinephrine-induced
      lipolysis associated with the translocation of hormone-sensitive lipase from the
      cytosol to lipid droplets in rat epididymal fat cells. In conclusion, RK prevents
      and improves obesity and fatty liver. These effects appear to stem from the
      action of RK in altering the lipid metabolism, or more specifically, in
      increasing norepinephrine-induced lipolysis in white adipocytes.

PMID- 15862605
TI  - Reduction of sulfamethoxazole and dapsone hydroxylamines by a microsomal enzyme
      system purified from pig liver and pig and human liver microsomes.
AB  - Biotransformation involving nitrogen are of pharmacological and toxicological
      relevance. In principle, nitrogen containing functional groups can undergo all
      the known biotransformation processes such as oxidation, reduction, hydrolysis
      and formation of conjugates. For the N-reduction of benzamidoxime an oxygen
      insensitive liver microsomal enzyme system that required cytochrome b5, NADH
      cytochrome b5 reductase and a cytochrome P450 isoenzyme of the subfamily 2D has
      been described. In previous studies it was demonstrated that N-hydroxylated
      derivates of strongly basic functional groups are easily reduced by this enzyme
      system. The N-hydroxylation of sulfonamides such sulfamethoxazole (SMX) and
      dapsone (DDS) to sulfamethoxazole-hydroxylamine (SMX-HA) and dapsone
      hydroxylamine (DDS-N-OH), respectively is the first step in the formation of
      reactive metabolites. Therefore it seemed reasonable to study the potential of
      cytochrome b5, NADH-cytochrome b5 reductase and CYP2D to detoxify these N
      hydroxylated metabolites by N-reduction. Metabolites were analysed by HPLC
      analysis. SMX-HA and DDS-N-OH are reduced by cytochrome b5, NADH-cytochrome b5
      reductase and CYP2D but also only by cytochrome b5 and NADH-cytochrome b5
      reductase without addition of CYP2D. The reduction rate for SMX-HA by cytochrome
      b5, NADH-cytochrome b5 reductase and CYP2D was 0,65 +/- 0,1 nmol SMX/min/mg
      protein. The reduction rate by b5 and b5 reductase was 0,37 +/- 0,15 nmol
      SMX/min/mg protein. For DDS-N-OH the reduction rate by cytochrome b5, NADH
      cytochrome b5 reductase and CYP2D was 1.79 +/- 0.85 nmol DDS/min/mg protein and
      by cytochrome b5 and NADH-cytochrome b5 reductase 1.25 +/- 0.15 nmol DDS/min/mg
      protein. Cytochrome b5, NADH-cytochrome b5 reductase are therefore involved in
      the detoxification of these reactive hydroxylamines and CYP2D increased the N
      reduction.

PMID- 15862606
TI  - Partial sleep deprivation compromises gastric mucosal integrity in rats.
AB  - The gastric mucosa is most susceptible to stress that has been shown to induce
      mucosal damage in humans and animals. This study aims to explore the underlying
      mechanisms of partial sleep deprivation, as a source of psychophysiological
      stress, on gastric functions and its effect on mucosal integrity. Sprague-Dawley
      rats were partially sleep deprived (PSD) for 7 or 14 days by housing inside
      slowly rotating drums. Gastric tissues and plasma were sampled at the end of the
      sleep deprivation periods and mucosal lesion scores were evaluated. Morphological
      examination was performed after Hematoxylin and Eosin staining. Plasma levels of
      noradrenaline, adrenaline, gastrin, histamine and somatostatin were determined
      with enzyme immunoassays. Gastric acidity was measured with acid-base titration
      in pylorus ligated rats. Gastric mucosal blood flow was evaluated with Laser
      Doppler Flowmetry. It was found that gastric lesions were induced in about 30%
      50% of the PSD rats. Gastric acidity as well as plasma levels of noradrenaline,
      gastrin and histamine were elevated. Gastric mucosal blood flow and plasma
      somatostatin level were on the contrary reduced, especially in rats with PSD for
      14 days. It is concluded that partial sleep deprivation compromises gastric
      mucosal integrity by increasing gastric acidity, plasma levels of noradrenaline,
      gastrin, histamine, and decreasing gastric mucosal blood flow. These results
      provided experimental evidence on the gastric damaging effects of PSD and it
      could be one of the risk factors contributing to gastric ulcer formation.

PMID- 15862607
TI  - Antioxidant activity of gallic acid from rose flowers in senescence accelerated
      mice.
AB  - The activities of the antioxidant enzymes catalase (CAT) and glutathione
      peroxidase (GPx) in the blood and liver of the aging model induced by injection
      of different doses of D-gal into normal mice, and in senescence accelerated mice
      (SAM) of different ages, were determined. The results showed that the enzyme
      activities in the D-gal treated mice did not alter appreciably but the enzyme
      activities in blood of the SAM declined significantly with the increase in age,
      especially in the 9-month-old SAM. When gallic acid purified from rose flowers
      was used to treat the 9-month-old male SAM, it not only reinstated the activities
      of CAT and GPx but also significantly reduced the amount of malondialdehyde (MDA)
      in the liver, brain and kidney. The results demonstrated that 9-month-old male
      SAM represent an appropriate animal model to evaluate the antioxidant activities
      of natural products.

PMID- 15862610
TI  - Practical applications of intravesical chemotherapy and immunotherapy in high
      risk patients with superficial bladder cancer.
AB  - The following steps are practical in the treatment of intermediate-to-high risk
      patients with superficial bladder cancer: Resect all visible tumor at the time of
      first TUR of bladder tumor. Strongly consider re-resection, especially for high
      risk, large, multifocal, stage T1 tumors. Apply one dose of cytotoxic
      chemotherapy perioperatively within 6 hours of TUR (ideally immediately). Once
      histopathology is available, consider intravesical induction chemotherapy for
      intermediate-risk patients and BCG for intermediate- or high-risk patients and
      those having failed prior chemotherapy. At least 1 year of maintenance therapy
      should be planned for all intermediate-to-high risk BCG-treated patients.
      Chemotherapy maintenance may be useful if perioperative chemotherapy was omitted.
      For patients failing standard therapy, a thorough discussion of the risks
      (including progression and metastasis) and expected benefits should take place
      before the initiation of salvage therapy. The radical cystectomy option should be
      openly entertained. Consider BCG plus interferon or gemcitabine-based salvage
      programs if appropriate. Explore clinical trial options. Contact urologic cancer
      experts for guidance and advice.

PMID- 15862611
TI  - Optimal management of the T1G3 bladder cancer.
AB  - TIG3 transitional cell carcinoma of the bladder represents a highly malignant
      tumor with a variable and unpredictable biologic potential. The most critical
      aspect of management requires a detailed discussion with the patient regarding
      the treatment options. Both the physician and the patient should be willing to
      reconsider the treatment options as the disease continues to evolve. In most
      cases initial management involves complete resection of the tumor, accurate
      staging of the disease, and intravesical immunotherapy or chemotherapy. Rigorous
      surveillance with long-term follow-up is crucial for managing these cases. In
      selected cases with adverse prognostic factors immediate cystectomy should be
      considered. The choice and timing of the decision to abandon bladder preservation
      and proceed with cystectomy should be continuously reconsidered on an individual
      patient basis, in concordance with the evolution of the disease (Fig. 1). The
      goal is to spare the bladder when possible but not at the risk of death from
      metastatic disease. Radical cystectomy in high-grade stage T1 transitional cell
      carcinoma offers excellent results in regard to the prevention of recurrence and
      progression and survival. Improvements in urinary diversion and nerve-sparing
      techniques have decreased the magnitude of social implications related to
      cystectomy in most patients regardless of gender. The discovery of reliable
      markers may contribute to better selection of patients for bladder sparing. Until
      then, the optimal treatment for the T1G3 tumor remains controversial.

PMID- 15862612
TI  - Radical cystectomy for bladder cancer: the case for early intervention.
AB  - There are no prospective studies comparing early cystectomy versus cystectomy
      after failed conservative management in patients with high-risk superficial
      bladder cancer. In the absence of clinically proven biomarkers for predicting
      tumor biology and the response to therapy, the treatment decision must be
      individualized based on the high-risk features outlined herein. Assuming that all
      patients can be treated effectively with bladder-sparing regimens and safely
      salvaged at the time of failure or progression is dangerous. Data support the
      negative impact of a delay in cystectomy and argue for improvements in the timing
      of cystectomy despite the clinical absence of muscle invasion. Accordingly, high
      risk patients with non-muscle invasive disease require vigilant follow-up and
      should be informed from the onset of the risk for progression and the possible
      need for cystectomy. Repeat resection before intravesical therapy in the patient
      with T1 tumor is advised and should help to improve, but will not completely
      eliminate, the problem of clinical under-staging. Among patients with CIS and
      recurrent high-grade non-muscle invasive tumors, repeat biopsies following
      intravesical therapy are encouraged to ensure treatment response. Although there
      is debate regarding the timing of early cystectomy for patients with high-risk
      non-muscle invasive bladder cancer, there is little doubt that, for muscle
      invasive disease, prompt cystectomy influences the effectiveness of this therapy
      choice. An unnecessary delay in the performance of radical cystectomy in patients
      with organ-confined bladder cancer compromises outcomes and risks potentially
      avoidable deaths from disease.

PMID- 15862613
TI  - Surgical factors in the treatment of superficial and invasive bladder cancer.
AB  - Tumor stage, grade, and variations in biologic behavior are primary features that
      largely determine bladder cancer outcomes. Quality of surgery used to assess and
      treat bladder tumors is critical to a successful outcome. Diagnosis, prognosis,
      local tumor control, and survival are highly dependent on surgical factors
      associated with the quality of surgical methods. In cases of superficial bladder
      tumors, this involves an aggressive TUR of all visible and suspected tumors,
      including a second resection in most cases. For invasive bladder cancers, radical
      cystectomy and a complete PLND are required. Both procedures require a high level
      of skill to achieve a successful outcome. Urologists have no control over the
      extent of disease or tumor biology, but can control how they evaluate and treat
      patients. The challenge is how to get better at maximizing surgical efforts. The
      who and how of surgery in bladder cancer does indeed matter.

PMID- 15862614
TI  - Clinical indications and outcomes with nerve-sparing cystectomy in patients with
      bladder cancer.
AB  - The autonomic sympathetic and parasympathetic nerve fibers from the pelvic plexus
      pass through the dorsomedial pedicle of the bladder ending as the paraprostatic
      neurovascular bundle or paravaginal plexus before supplying the urogenital
      diaphragm, sphincter, and erectile organs. Preservation of the autonomic
      innervation is important for sexual, lower urinary tract, and bowel function.
      Oncologic outcome is not compromised by a nerve-sparing cystectomy if adequate
      selection criteria are applied. During pelvic lymphadenectomy nerve sparing is
      not impaired as long as the dissection is performed on the lateral, not medial
      side of the ureters, where the nerves lie. Nerve-sparing radical cystectomy
      preserves sexual function and, in the case of orthotopic bladder substitution,
      better continence, and decreased catheterization rates (especially in women) are
      achieved. Therefore, under the proper circumstances, nerve-sparing radical
      cystectomy is to be strongly recommended.

PMID- 15862615
TI  - Neobladder with prostatic capsule and seminal-sparing cystectomy for bladder
      cancer: a step in the wrong direction.
AB  - A laudable trend in urologic surgical oncology is to minimize operative morbidity
      by anatomic and functional organ preservation without compromising radicality. An
      increasing number of authors have taken advantage of the sexual-function
      preserving cystectomy for bladder cancer. The modified procedure includes
      cystectomy with sparing of prostate, vasa deferens, seminal vesicles, and
      resection of a prostatic adenoma to avoid bladder outlet obstruction and bladder
      reconstruction with an orthotopic reservoir. This article focuses on studies from
      the last 15 years and includes the results from 13 centers worldwide. Many of
      them report a pattern of failure (local versus distant) that is highly unusual.
      Although a local recurrence rate of 7 of 252 patients is to be expected in this
      combined series the distant failure rate of 34 of 252 patients is at least twice
      as high as expected for the given series of superficial or organ-confined TCC.
      The observed distant failure rate of sexuality-preserving cystectomy in this
      potentially lethal disease is more than 5% higher as compared with standard
      radical cystectomy. The precise underlying mechanism of this unexpected pattern
      of failure following sexuality-sparing cystectomy is not fully understood.
      Furthermore, surgeons considering procedures that preserve a portion of the
      prostatic urethra, the prostatic capsule, or the entire prostate should recognize
      a 6% risk of significant prostatic cancer in any residual tissue, and the
      potential risk of urethral tumor involvement with TCC. Daytime continence
      following radical versus sexuality-sparing cystectomy is identical. Data on
      nighttime continence of sexuality-sparing cystectomy are inconclusive. The
      continuous intermittent catheterization rate following sexuality-sparing
      cystectomy, however, seems to be higher than after standard cystectomy. The only
      advantage sexuality-preserving cystectomy has is indeed preservation of these
      functions in a much higher percentage than following standard or nerve-sparing
      cystectomy. This is at the cost of radicality, however, and results in a 10% to
      15% higher oncologic failure rate. Consequently, sexuality-sparing cystectomy for
      bladder cancer is a step in the wrong direction and should be abandoned.

PMID- 15862616
TI  - The role of lymphadenectomy in high-grade invasive bladder cancer.
AB  - Radical cystectomy with bilateral pelvic iliac lymphadenectomy is a standard
      treatment for high-grade, invasive bladder cancer. Cystectomy arguably provides
      the best survival outcomes and the lowest local recurrence rates. Although the
      extent or absolute limits of the lymph node dissection are unknown and remain to
      be better defined, an ever-growing body of data supports a more extended
      lymphadenectomy at the time of cystectomy in all patients who are appropriate
      surgical candidates. An extended lymph node dissection should include the distal
      para-aortic and paracaval lymph nodes as well as the pre-sacral nodes, known
      anatomic sites of lymph node drainage from the bladder and potential sites of
      lymph node metastases in patients with bladder cancer. An extended dissection may
      provide a survival advantage in patients with node-positive and node-negative
      tumors without significantly increasing the morbidity or mortality of the
      surgery. The extent of the primary bladder tumor (p stage), the number of lymph
      nodes removed, and the lymph node tumor burden are important prognostic variables
      in patients undergoing cystectomy with pathologic evidence of lymph node
      metastases. Lymph node density may become an even more useful prognostic variable
      in these high-risk, node-positive patients with bladder cancer. This concept
      simultaneously incorporates the lymph node tumor burden (number of lymph nodes
      involved) and the number of lymph nodes removed (extent of the lymphadenectomy),
      improving the stratification of lymph node-positive patients following radical
      cystectomy. This notion may also be useful in future staging systems. Adjuvant
      therapies and clinical trials should consider applying these concepts, because
      they may help reduce bias and incorporate the extent of the lymphadenectomy,
      which currently is not standardized.

PMID- 15862617
TI  - Contemporary management of the urethra in patients after radical cystectomy for
      bladder cancer.
AB  - The incidence of urethral TCC after radical cystectomy is approximately 8%
      overall. The most important risk factor for urethral TCC after radical cystectomy
      and urinary diversion is prostatic involvement by TCC, particularly stromal
      invasion. The safety of using the urethra for orthotopic urinary diversion seems
      to be best when intra-operative frozen section analysis of the urethral margin is
      performed at the time of radical cystectomy. There is provocative but unconfirmed
      evidence that orthotopic urinary diversion may be protective against the
      development of urethral TCC. Although most urethral "recurrences" occur within 5
      years, delayed recurrences have been documented, mandating life-long follow-up of
      the retained urethra. Follow-up should include urinary cytology, either voided or
      urethral wash cytology as appropriate, with evaluation by endoscopy of any
      urethral related symptoms or change in voiding symptoms. The management of
      urethral TCC after cystectomy remains a total urethrectomy including excision of
      the meatus; however, in carefully selected patients with superficial disease and
      an orthotopic urinary diversion, urethra sparing may be attempted after a careful
      discussion with the patient. Survival after urethral TCC has generally been
      disappointing. The relative value of urethral versus original cystectomy
      pathologic stage and symptomatic versus nonsymptomatic recurrence in predicting
      survival remains controversial and awaits further studies that will most likely
      require the pooling of data from several large series.

PMID- 15862618
TI  - Quality of life issues in bladder cancer patients following cystectomy and
      urinary diversion.
AB  - HRQOL outcomes in bladder cancer patients undergoing cystectomy and urinary
      diversion are an important component in the critical assessment of bladder cancer
      treatment. To date, understanding of HRQOL in these patients remains poor.
      Although it is known that there are common factors that most likely affect HRQOL
      for all patients, it is unclear whether factors unique to a specific type of
      diversion impact HRQOL in a way that makes one type of diversion superior to
      another. Factors such as stoma maintenance, catheter use, urinary incontinence,
      body image, and sexual side effects are potentially different for each major type
      of diversion and most likely impact HRQOL, but a consistent advantage of one type
      of diversion over another has yet to be demonstrated. With slight changes in the
      approach to studying HRQOL outcomes, this question could be answered. Prospective
      study designs, appropriate adjustment for confounding factors, diverse patient
      populations, and the use of validated and disease-specific instruments would
      greatly enhance understanding of HRQOL in patients undergoing cystectomy for
      bladder cancer. By understanding these issues more completely, patients could be
      counseled not only about their predicted surgical risks and survival but also
      about the impact their disease will have on their longer-term quality of
      survival. Patients will then be able to make a more fully informed decision on
      the most appropriate form of therapy for this serious life-altering disease.

PMID- 15862619
TI  - The current and future application of adjuvant systemic chemotherapy in patients
      with bladder cancer following cystectomy.
AB  - Urothelial transitional cell cancer has a high rate of response to combination
      cytotoxic therapy. Approximately 50% of patients with high-grade bladder cancer
      and deep muscle invasion ultimately die of disseminated disease. Translating the
      high response seen in locally advanced disease into long-term survival in the
      metastatic setting and to improved survival in the advanced setting has proved
      difficult. This article reviews the use of adjuvant chemotherapy in localized or
      locally advanced transitional cell cancer. The chemotherapy of urological
      malignancies, including bladder cancer, has recently been reviewed in detail;
      this article does not contain an extensive review of the drugs used.

PMID- 15862620
TI  - Neoadjuvant chemotherapy in patients with invasive bladder cancer.
AB  - Neoadjuvant chemotherapy has been extensively investigated in muscle-invasive
      bladder cancer. When taken together, the randomized controlled trials of
      neoadjuvant cisplatin-based combination chemotherapy demonstrate an improved
      survival over cystectomy alone. In addition, neoadjuvant chemotherapy can result
      in downstaging of primary tumors. As noted, a pT0 disease status at cystectomy is
      associated with a significant improvement in survival. A randomized controlled
      trial comparing neoadjuvant to adjuvant cisplatin-based chemotherapy shows that
      neither approach is superior. Finally, the ongoing EORTC/SWOG adjuvant
      chemotherapy trial, when completed, should add importantly to the literature
      concerning the role of systemic chemotherapy in muscle-invasive bladder cancer.

PMID- 15862621
TI  - Clinical applications for targeted therapy in bladder cancer.
AB  - The tremendous amount of data accumulated through genomics, proteomics, and
      metabolomic technologies has not led to a definitive understanding of the
      mechanisms underlying cancer. The challenge remains as to how to integrate all of
      the relevant knowledge and data in a systematic manner so that researchers can
      gain the knowledge needed to devise the best therapeutic and diagnostic
      strategies. Human transitional cell carcinoma of the bladder is genetically
      heterogeneous, and it is surrounded by a complex tissue microenvironment
      involving vasculature, stromal cells, and connective tissue. One of the most
      challenging problems facing cancer researchers is the lack of correlation between
      in vitro cell lines and animal tumor models and human in vivo tumors. A few
      promising approaches are being devised that will help address this issue in the
      coming years. One such approach is the measurements of molecular levels of
      receptors, ligands, pathways components, and so on, directly in human tumors
      through in vivo imaging, or through proteomic profiling, as it has been proposed
      as standard protocol for cancer diagnostics and therapeutics.

PMID- 15862622
TI  - Methylphenidate regulates c-fos and fosB expression in multiple regions of the
      immature rat brain.
AB  - Methylphenidate (Ritalin, MPH) is a common psychostimulant used to treat
      childhood attention-deficit hyperactivity disorder (ADHD). Little is known about
      the long-term developmental effects on gene expression and behavior, which may
      occur with extended MPH use. We reported previously that the striatum is a major
      target of MPH, consistent with human MRI studies. In the present study, we tested
      the hypothesis that MPH is likely to have widespread effects in extra-striatal
      regions of the brain. We used the expression of two immediate early genes, c-fos
      and fosB, as probes to map the response of the immature rat brain to single (1
      day) versus repeated (14 days) MPH treatment (2 or 10 mg/kg; s.c.) from postnatal
      day 25 to 38. Consistent with previous reports, the striatum is a major target of
      acute MPH action, as indicated by elevated levels of cFOS-immunoreactivity (-ir).
      Increases in c-fos expression were also seen in the nucleus accumbens,
      cingulate/frontal cortex and piriform cortex, and Islands of Calleja. FosB
      expression was elevated only in the striatum following a single stimulation.
      Chronic MPH treatment (10 mg/kg/day for 14 days) resulted in an attenuation of c
      fos expression in the striatum and Islands of Calleja. However, levels of cFOS-ir
      remained elevated in the nucleus accumbens and frontal cortex. In contrast to the
      inhibitory effect of repeated MPH exposure on c-fos expression, FOSB-ir was
      further elevated in the striatum, and an increase was observed in the
      cingulate/frontal and piriform cortices. Thus, chronic MPH differentially
      regulated expression of c-fos and fosB in several brain regions. Our data suggest
      that MPH may exert its stimulant effects at multiple sites in the immature brain,
      which has implications for long-term treatment in children.

PMID- 15862623
TI  - Maternal thyroid hormone increases HES expression in the fetal rat brain: an
      effect mimicked by exposure to a mixture of polychlorinated biphenyls (PCBs).
AB  - Thyroid hormone is known to be essential for normal brain development both before
      and after birth, but much less is known about the role of thyroid hormone
      development before birth. In rodents, thyroid hormone of maternal origin can
      selectively regulate gene expression in the fetal cortex; HES1 was identified as
      a putative thyroid hormone responsive gene in the fetal cortex. Using in situ
      hybridization, we now confirm that thyroid hormone administration to pregnant
      rats can increase the abundance of HES1 mRNA in the fetal cortex on gestational
      day 16 (G16). In separate experiments, we found that maternal exposure to
      polychlorinated biphenyls (PCBs) increases HES expression similarly. Western
      analysis of proteins extracted from fetal cortex did not confirm that Notch-1 or
      Notch-3 activation was associated with treatment effects on HES expression.
      However, considering the role of HES proteins in fate specification of cortical
      neurons, these findings suggest that thyroid hormone, and PCB exposure, may
      influence fate specification of cortical neurons.

PMID- 15862624
TI  - Spatiotemporal patterns of expression of IGSF4 in developing mouse nervous
      system.
AB  - IGSF4 is a novel immunoglobulin (Ig)-like intercellular adhesion molecule. Since
      IGSF4 has been characterized by several independent research groups, this
      molecule is called by three names, TSLC1, SgIGSF and SynCAM. In the experiments
      to study global changes of gene expression in fetal murine brains after prenatal
      exposure to low-doses of X-rays, we have found IGSF4 as one of down-regulated
      genes after X-irradiation. In order to elucidate the expression of spatiotemporal
      expression of IGSF4 in the developing brain, we have produced polyclonal antibody
      against IGSF4 and studied the expression of IGSF4 with immunohistochemistry and
      Western blot analysis. At embryonic day (E) 12.5, IGSF4-immunoreactivity (IR) was
      observed diffusely in the telencephalic wall, whereas it became rather confined
      to the subplate, the cortical plate and the subventricular zone as the
      development proceeded. Noteworthy was a distinct radial pattern found in the
      cortical plate of E16.5. IGSF4-IR gradually decreased after birth and disappeared
      in adulthood. In the cerebellum, IGSF4 was expressed in the molecular layer at
      postnatal day (P) 0 through P14. By Western blot analysis, IGSF4 remained at low
      levels throughout embryonic stage, whereas it increased after birth. These
      spatiotemporal patterns of the expression suggest that IGSF4 plays crucial roles
      in the development of both telencephalon and cerebellum.

PMID- 15862625
TI  - Effect of hypoxia on the expression of pro- and anti-apoptotic proteins in
      neuronal nuclei of the guinea pig fetus during gestation.
AB  - The present study investigates the expression of apoptotic proteins Bax, Bad, Bcl
      2, and Bcl-xl following hypoxia in the cerebral cortex of the guinea pig fetus as
      a function of gestational age. Normoxic (Nx, n = 6) and hypoxic (Hx, n = 6)
      guinea pig fetuses at 35 and 60 days gestation were studied. Bax expression (OD X
      mm(2)) was 96.9 +/- 9.5 (Nx 35 days), 116.5 +/- 8.3 (Hx 35 days), P < 0.05 and
      116.2 +/- 3.4 (Nx 60 days, 144.6 +/- 11.7 (Hx 60 days), P < 0.05. Bad expression
      (OD X mm(2)) was 78.6 +/- 2.6 (Nx 35 days), 102.9 +/- 5.8 (Hx 35 days), P < 0.05
      and 101.5 +/- 4.3 (Nx 60 days), 139.8 +/- 7.9 (Hx 60 days), P < 0.05 vs. Nx 60
      days, also significantly higher from preterm hypoxia P < 0.007. Expression of Bcl
      2 (OD X mm(2)) was 27.4 +/- 2.0 (Nx 35 days), 28.0 +/- 2.4 (Hx 35 days), and 27.4
      +/- 2.7 (Nx 60 days), 29.7 +/- 2.3 (Hx 60 days). Expression of Bcl-xl (OD X
      mm(2)) was 51.0 +/- 4.4 (Nx 35 days), 46.1 +/- 8.0 (Hx 35 days) and 50.0 +/- 1.4
      (Nx 60 days), 54.9 +/- 7.4 (Hx 60 days). Hypoxia resulted in increased expression
      of the proapoptotic proteins Bax and Bad by 20% and 30% in the preterm as
      compared to 24% and 38% at term, without altering the expression of anti
      apoptotic proteins Bcl-2 and Bcl-xl. We conclude that the hypoxia-induced
      increased expression of Bax and Bad is greater at term compared to preterm.
      Furthermore, the hypoxia-induced increase in proapoptotic as compared to
      antiapoptotic proteins at term will accelerate the ongoing active process of
      programmed cell death at term compared to preterm gestation.

PMID- 15862626
TI  - Housekeeping gene expression during fetal brain development in the rat-validation
      by semi-quantitative RT-PCR.
AB  - Mammalian gene expression is usually carried out at the level of mRNA where the
      amount of mRNA of interest is measured under different conditions such as growth
      and development. It is therefore important to use a "housekeeping gene", that
      does not change in relative abundance during the experimental conditions, as a
      standard or internal control. However, recent data suggest that expression of
      some housekeeping genes may vary with the extent of cell proliferation,
      differentiation and under various experimental conditions. In this study, the
      expression of various housekeeping genes (18S rRNA [18S], glyceraldehydes-3
      phosphate dehydrogenase [G3PDH], beta-glucuronidase [BGLU], histone H4 [HH4],
      ribosomal protein L19 [RPL19] and cyclophilin [CY]) was investigated during fetal
      rat brain development using semi-quantitative RT-PCR at 16, 19 and 21 days
      gestation. It was found that all genes studied, with exception to G3PDH, did not
      show any change in their expression levels during development. G3PDH, on the
      other hand, showed increased expression with development. These results suggest
      that the choice of a housekeeping gene is critical to the interpretation of
      experimental results and should be modified according to the nature of the study.

PMID- 15862627
TI  - Partial rescue of neonatal lethality of Dhcr7 null mice by a nestin promoter
      driven DHCR7 transgene expression.
AB  - In humans, genetic disorders affecting post-squalene cholesterol biosynthesis
      result in a variety of dysmorphology syndromes. One key feature of all of these
      is the presence of mental retardation and another is the lack of a robust
      genotype-phenotype correlation. Knockout mice defective in the 3beta
      hydroxysterol Delta7 reductase (Dhcr7), a model for the most common of such
      disorders in humans, the Smith-Lemli-Opitz syndrome, all die within 24 h of
      birth. The cause of this postnatal mortality in these mice has not been fully
      established. In the present study, we tested the hypothesis that CNS dysfunction
      was a major cause of this lethality and investigated whether transgenic
      expression of normal human DHCR7 in neuronal tissues could rescue this neonatal
      lethality. Transgenic mice, expressing DHCR7 driven by murine nestin promoter,
      were bred onto Dhcr7 knock-out (Dhcr7(-1-)) background and resulted in a partial
      rescue of neonatal lethality in 11 of 91 (12%) of transgene-positive Dhcr7(-1-)
      pups. Despite biochemical analyses that showed continued profound cholesterol
      deficiency in brain, rescued animals survived between 3 and 17 days. Thus, one
      important conclusion to be drawn is that defects in CNS in Dhcr7 knockout mice
      may contribute to the early lethality. Another conclusion is that even small and
      subtle changes in the brain sterol metabolism were sufficient to enable rescue.
      These data also provide important clues as to the cause of the variable
      expressivity seen in SLOS.

PMID- 15862628
TI  - Gestation-induced cell proliferation in the rat brain.
AB  - The states of pregnancy and lactation bring about a range of physiological and
      behavioral changes in the adult mammal that prepare the mother to care for her
      young. In the present study, the effects of pregnancy on cell proliferation in
      the subventricular zone (SVZ) in female rats were examined. This region has been
      identified as a site of neurogenesis in adult rodents. To examine the
      proliferating cell population, control and pregnant rats were injected with
      bromodeoxyuridine (BrdU, 90 mg/kg, i.v.) and euthanized 1 h following injection.
      BrdU was visualized using diaminobenzidine. Changes in BrdU-labeled cells
      occurred in the female rat brain over pregnancy with significant increases found
      in the SVZ on day 21 when compared with cycling diestrous females. No changes
      were evident in the dentate gyrus of the hippocampus as a function of gestation.
      These data demonstrate that, in the rat, as in mice, gestation stimulates an
      increase in the number of new cells in selected regions of the central nervous
      system.

PMID- 15862629
TI  - Age dependence of pilocarpine-induced status epilepticus and inhibition of CaM
      kinase II activity in the rat.
AB  - This study was conducted to characterize the post-pubertal developmental aspects
      on seizure susceptibility and severity as well as calcium/calmodulin protein
      kinase type II (CaM kinase II) activity in status epilepticus (SE). Thirty- to
      ninety-day-old rats, in 10-day increments, were studied. This corresponds to a
      developmental age group that has not received thorough attention. The pilocarpine
      model of SE was characterized both behaviorally and electrographically. Seven
      criteria were analyzed for electrographical characterization: seizure severity,
      SE susceptibility, the average number of discrete seizures, average time until
      first seizure, average time to SE, average time from first discrete seizure to
      SE, and death. After 1 h of SE, specific brain regions were isolated for
      biochemical study. Phosphate incorporation into a CaM kinase II-specific
      substrate, autocamtide III, was used to determine kinase activity. There was no
      developmental effect on the average number of discrete seizures, average time
      until first seizure, average time to SE, average time from first discrete seizure
      to SE, and death; however, there was a significant effect on SE probability and
      seizure severity. Once SE was expressed, all animals showed a decrease in both
      cortical and hippocampal CaM kinase II activities. Conversely, seizure activity
      in the absence of SE did not result in a decrease in CaM kinase II activity. The
      data suggest that there is a gradual age-dependent modulation of SE
      susceptibility and seizure severity within the developmental stages studied.
      Additionally, once status epilepticus is observed at any age, there is a
      corresponding SE-induced inhibition of CaM kinase II.

PMID- 15862630
TI  - Markers for OLN-93 oligodendroglia differentiation.
AB  - Oligodendrocytes are target cells in the pathogenesis of multiple sclerosis (MS),
      a chronic demyelinating disease of the central nervous system (CNS). During the
      course of the disease, inflammatory mediators may damage oligodendrocytes and
      their myelin sheaths. Differentiation of oligodendrocyte progenitors is an
      important step in the process of remyelination. In the present study, OLN-93
      differentiation was studied in co-culture with C6 astrocytes as a natural source
      of growth and differentiation factors as well as after exposure to insulin-like
      growth factor-I (IGF-I). Morphological evaluation showed an increased degree of
      differentiation of OLN-93 cells after IGF-I administration, but not after co
      culture with astrocytes. During early differentiation, 2', 3'-cyclic nucleotide
      3'-phosphohydrolase (CNP) and zonula occludens-1 (ZO-1) tight junction protein
      expression were significantly increased. However, neither astrocyte co-culture
      nor exposure to IGF-I further increased the expression of these markers. Although
      reverse transcriptase-polymerase chain reaction revealed myelin basic protein
      (MBP) mRNA expression not to be affected during differentiation, we did find
      increased MBP protein expression by Western blotting. ZO-1 protein and DM20 mRNA
      levels were increased during the course of differentiation and after IGF-I
      administration. The present findings suggest that ZO-1 may be used as a marker
      for OLN-93 oligodendroglia differentiation.

PMID- 15862631
TI  - Apoptosis and necrosis in developing cerebellum and brainstem induced after focal
      cerebral hypoxic-ischemic injury.
AB  - Focal cerebral hypoxia-ischemia due to isolated vascular insufficiency is well
      known to cause ipsilateral, but not contralateral, cerebral apoptosis. Hypoxic
      ischemic damage to the cerebellum and brainstem in such a model has not been
      established. This experimental rodent study demonstrates, through
      deoxyribonucleic acid fragmentation and terminal deoxynucleotidyl transferase
      mediated deoxyuridine 5'-triphosphate-digoxigenin nick end labeling analysis,
      that neuronal cells in these infratentorial regions also suffer mild apoptosis
      and necrosis after focal cerebral hypoxic-ischemic injury in the newborn rat.
      These data provide additional insight into the mechanisms of neurological injury
      in the cerebellum and brainstem areas resulting from a focal cerebral hypoxic
      ischemic insult and demonstrate that future therapeutic interventions for hypoxic
      ischemic encephalopathy system should deal with the entire central nervous
      system.

PMID- 15862632
TI  - Administration of 17alpha-ethinylestradiol during pregnancy elicits modifications
      of maternal behavior and emotional alteration of the offspring in the rat.
AB  - Intraperitoneal administration of 17alpha-ethinylestradiol (15 microg.kg(-1)) in
      pregnant rats, every day from day 9 to day 14 of pregnancy, elicited a high
      percentage of abortions. Quantification of maternal behavior showed that treated
      dams took better care of their pups than control dams, injected with the vehicle
      only, did. Postnatal reflexes, which reflect maturational rate, were established
      more promptly in the offspring of treated dams than in the offspring of control
      dams. However, when adult, the rats born from treated dams developed anxiety- and
      depressive-like behaviors. All these results are explained by the effects of the
      exogenous estrogen on the developing brain of the fetuses.

PMID- 15862633
TI  - Expression of Fgf19 in the developing chick eye.
AB  - Fibroblast growth factor 19 (FGF19) is a new member of the FGF family of growth
      factors. Here, we describe the localization of Fgf19 mRNA in the developing chick
      retina and lens in stages from the Hamburger and Hamilton stage 15 (HH15) to
      postnatal day 30 (P30). Fgf19 was expressed in a transient manner in postmitotic
      neuroblasts during the migration from the ventricular surface to their final
      location. Moreover, from HH31 (embryonic day 7, E7) on, a subset of lined up
      Fgf19 expressing cells was distributed in the outer region of the presumptive
      INL. These cells were Pax6 immunoreactive horizontal cells. During the last third
      of embryogenesis, Fgf19 expression in the retina was progressively down-regulated
      and was not detected at P30. Also, it was transiently expressed in the equatorial
      region of the lens.

PMID- 15862634
TI  - Globalisation, health policy and the exercise of power--a second opinion on
      Gilbert and Gilbert (2004).

PMID- 15862635
TI  - Public opinion on alcohol service at licensed premises: a population survey in
      Stockholm, Sweden 1999-2000.
AB  - OBJECTIVE: In 1996, a community alcohol-prevention program focusing on licensed
      premises was initiated in Stockholm, Sweden. As a part of this initiative, a
      study has been conducted to investigate the public opinion in Stockholm on
      different strategies to reduce problems related to alcohol service at licensed
      premises. METHOD: A random sample of 1000 people resident in Stockholm County,
      within the age-group 18-65 years was selected. A postal questionnaire was sent
      out during the time-period November 1999 and January 2000 (response rate 59%).
      The questionnaire included questions on background factors, and support for
      various strategies to reduce intoxication and to prevent violence at licensed
      premises. The impact of each background factor on level of support for each
      strategy was analyzed using logistic regression. RESULTS: We found an overall
      strong support for licensed premises to practice responsible beverage service to
      reduce intoxication, whereas strategies to reduce availability (e.g., increased
      alcohol price, reduced open hours) were unpopular. The level of support differed
      by background factor. Frequent alcohol consumers, men, young people (< or =30
      years), and frequent visitors to licensed premises, were less supportive.
      CONCLUSION: There is strong popular support for licensed premises to practice
      responsible beverage service and for stricter enforcement of existing legislation
      by local authorities.

PMID- 15862636
TI  - SARS in Singapore: surveillance strategies in a globalising city.
AB  - Public health measures employed to fight against the spread of SARS need to be
      guided by biomedical knowledge as well as an understanding of the social science
      aspects of the disease. Using Singapore as a case study, we explore how the state
      constructs the disease and implements measures targeted at creating a ring of
      defense around the island and using surveillance to monitor and prevent its
      spread. While there is support, there is also resentment among some Singaporeans
      who complain that their right to privacy has been invaded and that over
      surveillance may have actually occurred. Marginalisation and discrimination have
      not only affected the local population but in this open economy which is striving
      to achieve global city status, businesses, tourism, foreign talent, foreign
      contract workers and foreign students studying in Singapore have also been
      negatively affected. While Singapore has been applauded by WHO and used as an
      example of quick and effective response, a holistic approach to the management of
      infectious disease must address the social implications of strategies that are
      drawn from medical knowledge alone because it impinges on the social lives of
      people and how people interact with each other under stressful circumstances.

PMID- 15862637
TI  - The effects of patient cost sharing on ambulatory utilization in South Korea.
AB  - This study focused mainly on the effects of patient cost sharing on the demand
      for physician service, especially in the low-income people. Patient cost sharing
      is one of the policies used extensively in the health care financing in Korea,
      which has been adopted to control the health care cost. It has raised the
      argument that cost sharing inhibits low-income patients' access to affordable
      medical care. Data from the National Health and Nutrition Survey conducted 1998
      by the Korean Ministry of Health and Welfare was used for this analysis. Multiple
      regression was done with the dependent variable of the amount of ambulatory
      utilization and price elasticities are estimated. We obtained significant out-of
      pocket price elasticities depending on patient income levels and types of care
      facilities in the range of -0.21 to -0.07, -0.20 to -0.10, respectively. We found
      out that low-income patients are more sensitive to cost sharing than high-income
      patients. Furthermore, we found out that the users of general hospitals are less
      sensitive to cost sharing than the users of clinics. These results shows that the
      cost sharing policy in Korea does not efficiently work. Patient cost sharing in
      Korea induces inequitable medical service utilization and also it does not
      decrease moral hazard in the sense that the higher cost-sharing sector is less
      sensitive to cost sharing.

PMID- 15862638
TI  - Heterogeneities in the production of health: smoking, health status and place.
AB  - The harmful effects of smoking on health are well-established. However, little
      attention has been given to possible variations in the size of the association
      within populations. In this paper, we test for neighbourhood variation in the
      smoking-health relationship. We estimate equations to explain variations in self
      reported health using data from a survey of adults in four distinct neighbourhood
      clusters in Hamilton, Ontario. After controlling for neighbourhood composition,
      the probability of being unhealthy remained significantly higher in the two lower
      socioeconomic status neighbourhoods (North East and Downtown) than in the rest of
      the city. The smoking-health association was not the result of more smokers
      living in less healthy neighbourhoods. In the Downtown neighbourhood, the
      relative odds of being unhealthy among smokers compared to non-smokers was less
      than one-half of the corresponding relative odds in the rest of the city.
      Although smoking represents a health risk for individuals in all neighbourhoods,
      for individuals living in the Downtown neighbourhood the size of this risk is
      substantially smaller than for individuals in other neighbourhoods.

PMID- 15862639
TI  - The global-local dilemma of a Ministry of Health experiences from Uganda.
AB  - Despite extensive reforms, including an overall decentralization of government,
      health services and health status remain largely unchanged in Uganda. Given its
      dependence on international resources, policies and paradigms, the Ministry of
      Health (MOH) paradoxically disembeds itself increasingly from the local community
      while attempting to improve its local connections. This article suggests a model
      for understanding and addressing these difficulties.

PMID- 15862640
TI  - Provider type and depression treatment adequacy.
AB  - We investigate the effect of initial provider (psychiatrist versus primary care
      physician or non-physician mental health specialist) on the adequacy of
      subsequent treatment for persons with depression. Our data are from MarketScan, a
      medical and pharmacy insurance claims database, which we use to estimate models
      of the likelihood of treatment for depression and the likelihood that any anti
      depression treatments received are adequate. Patients initially seeing
      psychiatrists are most likely to receive adequate treatment. Provider type has a
      statistically and medically significant effect on whether any treatment occurs
      but a smaller effect on treatment adequacy among treated patients. Our results
      show the importance of provider type in treatment patterns, but the effects on
      patient outcomes are yet to be determined definitively.

PMID- 15862641
TI  - The relevance and prospects of advancing tobacco control in Indonesia.
AB  - Using published data about consumption, economic aspects, and legislation, this
      paper analyzes tobacco control in Indonesia, a major consumer and producer of
      tobacco products. Given its large population and smoking prevalence, Indonesia
      ranks fifth among countries with the highest tobacco consumption globally. Over
      62% of Indonesian adult males smoke regularly, contributing to a growing burden
      of non-communicable diseases and enormous demands on the health care system.
      Tobacco control policies, however, have remained low on the political and public
      health agenda for many years. One reason was the contribution of tobacco to
      government revenues and employment, particularly in the industrial sector. But
      tobacco's importance in employment has fallen significantly since the 1970s from
      38% of total manufacturing employment compared with 5.6% today. Widespread use of
      tobacco since the 1970s and the concomitant burden of non-communicable diseases
      have given rise to a more balanced view of the costs and benefits of tobacco
      production over the last decade. The first tobacco control regulation passed in
      1999, succeeded by amendments in 2000 and 2003. Today, few restrictions exist on
      tobacco industry conduct, advertising, and promotion in Indonesia. We examine the
      relevance and prospects of advancing in Indonesia four cost-effective tobacco
      control strategies: price and tax measures, advertising bans, clean air
      legislation, and public education. We conclude with several suggestions for
      action for the public health community.

PMID- 15862642
TI  - Voluntary or compulsory health care reform? The case of primary care
      organisations in Scotland.
AB  - Previous studies have suggested that voluntary reform of the delivery of primary
      care services is more likely to occur in affluent areas. Health system reforms
      that include voluntary participation of GPs may therefore lead to a two-tier
      service in terms of access to and utilisation of medical services. New primary
      care organisations in Scotland (local health care co-operatives) were introduced
      in 1999. These are groups of general practices and membership was voluntary. The
      aim of this study is to examine whether the voluntary nature of membership was
      likely to exacerbate or reduce inequalities in the provision of primary care
      services. Logistic regression analysis was used to identify differences in
      population, practice, and GP characteristics between general practices that have
      joined a co-operative and those that have not. The results indicated that
      practices located in deprived areas and covering populations with high levels of
      morbidity were more likely to join a co-operative. High workload decreased the
      probability of membership. General practices that found it difficult to obtain
      access to local authority residential care homes were more likely to join a co
      operative. The number of fee claims for minor surgery sessions per whole-time
      equivalent GP increased the probability of membership. There is therefore some
      evidence indicating that general practices located in areas of high need are more
      likely to join a co-operative. This suggests that voluntary participation in
      these new primary care organisations may reduce rather than exacerbate
      inequalities in the provision of primary care.

PMID- 15862643
TI  - Administrative and financial responsibilities for sheltered housing for mentally
      ill and handicapped persons in Germany and its impact on housing supply.
AB  - BACKGROUND: The integration of mentally ill and handicapped persons in the
      society requires the availability of various forms of sheltered housing in the
      community, most important ambulatory (supported) housing facilities. In Germany
      the administrative and financial responsibility for sheltered housing for mental
      ill and handicapped persons is usually assigned to two authorities: the welfare
      authorities at Lander (state) level are responsible for hostels, the welfare
      authorities on community and district level are responsible for ambulatory
      housing. However some Lander have distributed these responsibilities differently
      and other Lander offer subsidy programmes to promote the implementation of
      ambulatory housing. OBJECTIVE: To evaluate the different modes of distributing
      the responsibilities for administration and financing of sheltered housing for
      their impact on the supply with ambulatory and stationary housing in the 16
      German Lander. METHOD: (1) Analysis of the practise of distributing the
      responsibilities for housing between Lander and community welfare-authorities in
      the 16 Lander. Analysis of the subsidy programmes in the Lander that aim to
      promote the implementation of ambulatory housing. (2) Assessment of the
      capacities in housing for mentally ill and handicapped persons in the Lander. (3)
      Comparing (1) and (2). RESULTS AND DISCUSSION: Lander that have the
      responsibilities for ambulatory housing and for hostels organised on the same
      authority-level, offer generally more housing in ambulatory facilities and less
      in hostels than Lander that do not. However, three Lander, despite having all
      responsibilities for housing at one authority level, provide accommodation for
      mentally ill and handicapped persons predominantly in hostels. There are so far
      no indications whether it would be more favourable to have a unique authority for
      housing based on Lander or on community level. Subsidy programmes to promote the
      implementation of supported housing are successful if they sponsor at least 50%
      of costs and if they exist for a considerable duration of time. CONCLUSION:
      Organising the responsibilities for housing for mental ill and handicapped
      persons on one authority level and the availability of subsidy programmes have a
      positive impact on the supply with ambulatory housing. However other factors also
      have to be considered to influence the supply with ambulatory housing, such as
      political will, attitudes towards the mentally ill, interests of hostel
      operators, pre-existing hostel infrastructure, available funds. These factors
      need to be researched further.

PMID- 15862644
TI  - Medical savings accounts and the Canada Health Act: complimentary or
      contradictory.
AB  - The publicly funded health system in Canada, almost since inception, has been the
      focus of numerous critiques, matched only by the solutions offered, and the
      secondary problems generated. One of the proposed solutions is the use of medical
      savings accounts (MSAs). It is reasoned that MSAs will make Canadians more
      accountable for the health services they utilize, yield cost containment, and
      potential savings. However, before a nation-wide, public MSA can be considered
      further, there is need to reconcile the following: (a) empirical evidence in
      support of MSAs that is not as compelling as some of its proponents argue; (b)
      the scale and complexity of a MSA if integrated into a publicly funded, nation
      wide health system in a country the size of Canada; (c) whether the cost to
      formulate, implement, and operate a nation-wide Canadian MSA would yield the net
      gains to warrant such an expenditure; (d) the fact that implementation of a
      nation-wide MSA potentially may contravene the Canada Health Act.

PMID- 15862645
TI  - Quantification of multiple sclerosis lesion load and brain tissue volumetry using
      multiparameter MRI: methodology and reproducibility.
AB  - Quantitative characterization of multiple sclerosis (MS) lesion load is of
      considerable interest to clinical follow-up studies. Based on fuzzy clustering of
      multiparameter magnetic resonance images, we have developed a computer-assisted
      system for volumetric quantification of brain tissue. Tests on patient data show
      that the system is very efficient, and volumetric measurements characterized are
      highly reproducible. The high reproducibility and efficiency offer the potential
      of routine laboratory and clinical use for quantification of MS lesion load.

PMID- 15862646
TI  - Frequency-shift based detection of BMS contrast agents using SSFP: potential for
      MRA.
AB  - A novel mechanism of MRI contrast enhancement, based on the detection by a
      balanced steady-state free precession (SSFP) sequence of the proton resonance
      frequency shift induced by bulk magnetic susceptibility (BMS) contrast agents,
      was investigated. The potential for this contrast mechanism to image blood
      vessels was explored. The relaxation time and the frequency shift effects of
      gadolinium- and dysprosium-DOTA on SSFP signal was first simulated and evaluated
      on a water phantom at 1.5 T. In vitro, a 5-mM concentration in contrast agent
      induced a 20-Hz frequency shift, leading to a signal increase of 92% for Dy-DOTA,
      and a 10-Hz frequency shift, leading to a signal increase of 58% for Gd-DOTA at
      the reference frequency, taking into account the nonlinear SSFP signal response
      on frequency offset. The concept was then evaluated in vivo on anesthetized
      rabbits. Low doses of dysprosium-DOTA were injected in their vascular system, and
      imaging was performed at the level of neck vessels. Following a bolus injection,
      mean signal changes of 31%, 20% and 14% were observed in the carotid arteries,
      the vertebral veins and the jugular veins, respectively. The bolus peak times in
      arteries and veins were consistent with the rabbit vascular circulation. This
      frequency-shift based contrast mechanism presents interesting potential for
      contrast-enhanced MR angiography (CE-MRA) compared to usual relaxation-based
      contrast, but further investigations on reproducibility will be necessary.

PMID- 15862647
TI  - Diffusion-weighted three-dimensional MP-RAGE MR imaging.
AB  - The advantages of three-dimensional (3D) acquisition are that you obtain thinner
      and more slices with better profiles, and better signal-to-noise ratio for an
      equivalent slice thickness. Three-dimensional acquisition is preferable for
      obtaining contiguous thin-slice MR images. However, the acquisition time extends
      compared with the two-dimensional acquisition because the second phase-encode
      axis is applied by the 3D acquisition. Therefore, 3D acquisition should be a high
      speed imaging method. In this paper, a new diffusion-sensitive 3D magnetization
      prepared rapid gradient-echo (3D MP-RAGE) sequence was studied. In this sequence,
      a preparation phase with a 90 degrees RF-motion proving gradient (MPG): MPG-180
      degrees RF-MPG-90 degrees RF pulse train (diffusion-weighted driven-equilibrium
      Fourier transform) was used to sensitize the magnetization to diffusion. Centric
      k-space acquisition order is necessary to minimize saturation effects from
      tissues with short relaxation times. From phantom experimental results, the
      effect of the diffusion weighting was changed by the centric vs. sequential k
      space acquisition order. The effect of centric k-space acquisition order was
      larger than the effect of sequential k-space acquisition order. The contrast of
      centric k-space acquisition order became equal to the contrast of conventional
      diffusion-weighted spin echo. From rat experimental results, small isotropic
      diffusion-weighted image data (voxel size: 0.625 x 0.625 x 0.625 mm3) were
      obtained. This sequence was useful in vivo.

PMID- 15862648
TI  - Optimizing brain MRI protocols in the follow-up of patients with multiple
      sclerosis T2-weighted MRI of the brain after the administration of gadopentetate
      dimeglumine.
AB  - The aim of our study was to determine whether T2-weighted (T2w) MRI of the brain
      could be performed immediately after the administration of gadopentetate
      dimeglumine (gadolinium DTPA) in patients with multiple sclerosis (MS) without a
      loss in image quality or diagnostic reliability. Sixteen patients with clinically
      diagnosed MS were included in the study. Twenty-four patients with various
      cerebral pathologies (14 patients with multiple lacunar lesions) were examined in
      order to exclude masking of T2 hyperintense lesions other than MS lesions. Images
      of 10 patients without pathological changes served as a control condition for the
      qualitative analysis. In these 50 patients, T1w and T2w MRI was performed before
      and after the administration of gadolinium DTPA. Signal intensities were measured
      within T2 hyperintense cerebral lesions, in T1-enhancing lesions and in normal
      appearing brain tissue on T2w turbo spin-echo (TSE) sequences. Both quantitative
      and qualitative analysis did not show significant differences between T2w pre-
      and postcontrast series. T2w MRI performed prior to and after the administration
      of gadolinium DTPA provides similar information in patients with MS. With a TR of
      3.2 s, not a single lesion was obscured on T2w postcontrast series. Acquisition
      of T2w MR images immediately after the administration of gadolinium DTPA allows
      for shorter examination time and assures sufficient time for contrast enhancement
      in cerebral lesions with a disrupted blood-brain barrier.

PMID- 15862649
TI  - A method to investigate intervertebral disc morphology from MRI in early
      idiopathic scoliosis: a preliminary evaluation in a group of 14 patients.
AB  - The aim of the study was to implement a methodology to quantify in vivo and from
      magnetic resonance imaging (MRI) the 3D geometrical properties of intervertebral
      discs (IVDs) in early idiopathic scoliosis with small curves. MRI data were
      posttreated using a custom-made image processing software to semiautomatically
      determine the location of disc centres, the location of the nucleus pulposus (NP)
      and the ratio between the NP volume and the disc volume. MRI was performed in a
      clinical protocol involving 14 patients having an early idiopathic scoliosis.
      First, the 3D reconstruction errors were quantified using a reproducibility test
      (intraoperator and interoperator) in one IVD (L5-S1). The maximal errors in
      location were 0.79 mm in the frontal plane, 1.84 mm in the sagittal plane and
      0.76 mm in the vertical plane. The maximal error in relative volume was 42%.
      Second, the nucleus migration and relative volume were quantified in discs T5-T6
      to L5-S1. No significant relative volume variation was detected. Concerning the
      disc migration, no significant differences were found in the sagittal and axial
      planes. In the frontal plane, significant differences were observed at the apex
      of the scoliotic curvature when the Cobb angle was > or =20 degrees . This
      innovative study in early scoliosis showed reproducible preliminary results, and
      its application to improve diagnosis and follow-up will be established in an
      enlarged patient database.

PMID- 15862650
TI  - An alternative viewpoint of the similarities and differences of SVD and FT
      deconvolution algorithms used for quantitative MR perfusion studies.
AB  - Quantitative cerebral blood flow (CBF) values can be determined from residue
      function estimates obtained from magnetic resonance dynamic susceptibility
      contrast (DSC) perfusion studies using a variety of deconvolution approaches.
      However, there are significant differences between the CBF estimates obtained,
      differences that are not simply due to minor details of the implementation of the
      algorithms. The standard singular value decomposition (sSVD) shows a variation of
      CBF values with arterial-tissue delay (ATD) not present with the Fourier
      transform deconvolution algorithm. Fourier transform deconvolution and the newly
      suggested delay-invariant SVD algorithm implementations provide CBF estimates
      whose accuracy changes with tissue mean transit times (MTTs). Techniques
      combining sSVD with deliberate ATD manipulation have been proposed to compensate
      for this inaccuracy. Other studies indicate that CBF changes related to slice
      position in a multislice study, and other experimental factors, can be reduced
      using interpolative deconvolution algorithms. In this review, we use both time
      domain and frequency-domain analysis to show the underlying theoretical
      relationships between these many approaches to obtain "the best" CBF estimate.
      This model allows us to better understand the similarities and differences,
      advantages and disadvantages between these variants of the deconvolution
      algorithms used in DSC perfusion studies.

PMID- 15862651
TI  - RF artifacts caused by metallic implants or instruments which get more prominent
      at 3 T: an in vitro study.
AB  - Metallic devices with high electrical conductivity inside or adjacent to the body
      might lead to marked alterations of the RF amplitude B1 in the tissue under
      investigation, especially at increased RF frequency, and if specific conditions
      for electromagnetic resonance are fulfilled. RF-metal interaction effects were
      investigated systematically at B0=0.2, 1.5 and 3 T analyzing correlated image
      artifacts for copper wires (d=1 mm, L=53 and 27 cm), and for following
      instruments and implants made of titanium or nitinol: biopsy needles, hip
      prostheses, vascular stents and aneurysm clips. The samples were examined in Gd
      DTPA-doped 140 mM NaCl solution using spin-echo (SE) sequences with high readout
      bandwidth. Automatic transmitter adjustment V(T,auto) and manually reduced
      transmitter voltage VT were applied in order to detect B1 enhancement. At 0.2 T,
      beyond the shielding of the luminal region of the stents, no RF effects were
      observed. At 1.5 T, the copper wires caused distinct RF artifacts. At 3 T, RF
      artifacts also appeared for the hip prostheses and the biopsy needles. Stents
      with pronounced luminal shielding at lower field strength revealed marked B1
      enhancement close to their outer surface.

PMID- 15862652
TI  - A proton NMR relaxation study of hen egg quality.
AB  - A quantitative analysis of NMR proton relaxation in hen egg albumen and yolk is
      undertaken to research the causes of quality loss during the first few days of
      storage and to access the feasibility of an on-line NMR sensor of internal egg
      quality. It is shown that the change in the transverse relaxation in thick egg
      albumen mainly results from an increase in proton exchange rate resulting from a
      pH increase attributed to loss of carbon dioxide by diffusion through the
      eggshell. The results suggest that the low-field T1 is the best relaxation time
      indicator of albumen quality.

PMID- 15862653
TI  - Multiple focal nodular hyperplasia syndrome: diagnosis with dynamic, gadolinium
      enhanced MRI.
AB  - We present a rare case of multiple focal nodular hyperplasia (FNH) with greater
      than 20 FNH lesions and coexistent liver hemangiomata. Particular attention is
      paid to the MRI characteristics of this disease process and the features of
      "multiple FNH syndrome" are discussed.

PMID- 15862654
TI  - MRI findings of primary small-cell carcinoma of kidney.
AB  - We report the MRI findings of primary small-cell carcinoma of the kidney (PSCCK)
      in a 59-year-old female. This tumor appeared as a 16-cm mass that arose from the
      right kidney. This lesion had diminished signal on T1-weighted images and
      heterogeneous mixed signal on T2-weighted images. The tumor primarily involved
      the renal medulla with persistent thin renal cortex. Despite the tumors' large
      size, no substantial central necrosis was present. The predominant medullary
      location and the lack of central necrosis in this large tumor were features
      unusual for renal cell carcinoma and should raise the suspicion of another
      malignancy, the differential diagnosis of which should contain extrapulmonary
      small-cell carcinoma of the kidney.

PMID- 15862655
TI  - Proceedings of the 15th International Symposium on Pharmaceutical and Biomedical
      Analysis. May 2-6, 2004. Florence, Italy.

PMID- 15862656
TI  - A new approach to the rest potential of biological membranes.
AB  - In a series of recent papers, Bonciocat et al., have shown that the faradaic
      current density of an electrode redox reactions occurring with combined
      limitations, of charge transfer and nonstationary linear, semi-infinite
      diffusion, is the solution of an integral equation of Volterra type. This
      integral equation has been transformed to describe the transport of ions through
      the interface between two immiscible electrolytic solutions. According to
      Goldman, Hodkin, Katz theory, the rest potential of a biological membrane is
      determined by the maintenance of different concentrations of the ions Na+, K+ and
      Cl-, in the two aqueous solutions separated by the membrane. Using the integral
      equations (of Volterra type) for the ionic current densities iNa, iK, iCl, and
      applying the open circuit condition (i.e., iNa + iK + iCl = 0), the potential
      differences at the junctions: aqueous solution (I)/membrane, respective
      membrane/aqueous solution (II), have been obtained. To get the diffusion
      potential across the membrane, the Planck's theory has been used. The sum of
      these three contributions gives the expression of the rest potential (and a
      comparison with the Goldman-Hodkin-Katz formula is made, showing in what
      conditions they become identical formulae).

PMID- 15862657
TI  - Enantioselective LC analysis of synephrine in natural products on a protein-based
      chiral stationary phase.
AB  - An enantioselective LC method with photodiode array detection (PAD) was developed
      for the enantioseparation of (+/-)-synephrine from C. aurantium L. var. amara
      fruits and phytotherapic derivatives by using a protein-based chiral stationary
      phase with cellobiohydrolase as the chiral selector (Chiral-CBH). Analyses were
      carried out on a Chiral-CBH column (100x4.0 mm i.d., 5 microm), with a mobile
      phase consisting of 2-propanol (5%, w/w) in sodium phosphate buffer (pH 6.0; 10
      mM) and disodium EDTA (50 microM). The flow rate was 0.8 mL/min. Detection was
      set at 225 nm. To identify the order of elution, the racemate was resolved by the
      preparation of suitable diastereoisomeric salts with antipodes of appropriate
      organic acids. Isolation of synephrine from C. aurantium fruits and phytoproducts
      was performed by solid-phase extraction (SPE) with a strong cation-exchange
      phase. The method developed was validated and was found to be linear in the 0.40
      40.14 microg/mL range (r2=1.000, P<0.0001) for both synephrine enantiomers. The
      limit of detection (LOD) for each enantiomer was 0.04 microg/mL. The limit of
      quantification (LOQ) for each enantiomer was 0.13 microg/mL. Intra-day precision
      (calculated as %R.S.D.) ranged from 0.03 to 0.24% for (-)-synephrine and from
      0.03 to 0.35% for (+)-synephrine. Inter-day precision (calculated as %R.S.D.)
      ranged from 0.07 to 1.45% for (-)-synephrine and from 0.06 to 1.26% for (+)
      synephrine. Intra- and inter-day accuracies (calculated as %recovery) were in the
      ranges of 97.4-100.6 and 98.0-101.6% for (-)-synephrine, and in the ranges 97.0
      101.5 and 98.1-102.8% for (+)-synephrine. The results of the application of the
      method to the analysis of C. aurantium samples showed that (-)-synephrine was the
      main component. (+)-Synephrine was not detected in C. aurantium fruits and was
      present in low concentration in the phytoproducts.

PMID- 15862658
TI  - High-performance liquid chromatographic determination of ciprofloxacin in plasma
      samples.
AB  - A new bioanalytical high-performance liquid chromatographic (HPLC) method for the
      determination of ciprofloxacin with norfloxacin as an internal standard was
      developed and validated for plasma samples. Norfloxacin is structural homologue
      of ciprofloxacin and exhibits similar retention properties. The quality of
      respective peak separation is strongly influenced by amphoteric character of
      ciprofloxacin and norfloxacin as well. In previously published HPLC methods on
      conventional C18 reversed-phase [F. Belal, A.A. Al-Majed, A.M. Al-Obaid, Talanta
      50 (1999) 765-786; G. Carlucci, J. Chromatogr. A 812 (1998) 343-367], ion pair
      reagents were added into the mobile phase to suppress peak tailing. In comparison
      with endcapped and high purity silica reversed-phase sorbent (Purospher RP-18e,
      Merck), which yielded symmetrical peaks, separation efficiency was further
      enhanced in our method. Gradient elution mode using acetonitrile and phosphate
      buffer pH 3 on the pentafluorophenylpropyl stationary phase (250-4.6 mm Discovery
      HS F5, 5 microm, Supelco) was carried out. The resolution of 4.1 for
      ciprofloxacin-norfloxacin peaks was achieved. Sample preparation by SPE C18
      (Supelclean) with recovery 72% was performed. Fluorescence detection with
      lambda(excit)=280 nm, lambda(emis)=446 nm was used. After the validation, the
      bioanalytical HPLC method was applied to pharmacokinetic studies.

PMID- 15862659
TI  - Validation in pharmaceutical analysis. Part II: Central importance of precision
      to establish acceptance criteria and for verifying and improving the quality of
      analytical data.
AB  - Validation of analytical procedures is a vital aspect not just for regulatory
      purposes, but also for their efficient and reliable long-term application. In
      order to address the performance of the analytical procedure adequately, the
      analyst is responsible to identify the relevant parameters, to design the
      experimental validation studies accordingly and to define appropriate acceptance
      criteria. Establishing an acceptable analytical variability for the given
      application is of central importance as many other acceptance criteria can be
      derived from such a precision. Acceptable precision ranges for types of control
      tests and/or analytes can be obtained from validation, but also related
      activities such as transfer, control charts, or extracted from routine
      applications such as batch release or stability studies (data mining). Apart from
      compiling a database for general benchmarking, during such an information
      building process, the reliability of the analytical variability of the specific
      procedure is more and more increased. This is important as a reliable target
      variability facilitates to detect or investigate atypical or out-of specification
      behaviour of analytical data in a routine application, thus improving the data
      quality and reliability. According to the life-cycle concept of validation,
      measures should be taken to maintain and control the validated status of
      analytical procedures during long-term routine application, such as monitoring
      relevant performance parameters (system suitability tests), control charts, etc.
      If the analytical system is demonstrated to be stable, i.e. under statistical
      control, a major variability contribution in LC originating from the standard
      preparation and analysis can be reduced. A concept of quantification by pre
      determined calibration parameters instead of the classical approach of
      simultaneous calibration is described.

PMID- 15862660
TI  - Combined pH/organic solvent gradient HPLC in analysis of forensic material.
AB  - A combined pH/organic solvent linear gradient mode in high performance liquid
      chromatography (HPLC) is presented as a new approach to determination of low
      concentrations of ionogenic analytes in biological material. The approach
      consists in simultaneous development of linear gradients of pH and organic
      modifier in the mobile phase. Advantages of the method are illustrated in
      postmortem analysis of opipramol in material from suicide victims. Very narrow
      peaks without tailing were obtained and several times lower limits of analyte
      quantitation were achieved using ultraviolet detection as compared to a standard
      isocratic method. The double gradient HPLC method seems to be especially valuable
      in case of ionogenic analytes dispersed in complex biological matrices. That is
      due to a high selectivity of the double gradient method and the lack of peak
      tailing, which is commonly observed for basic analytes chromatographed at
      isocratic conditions.

PMID- 15862661
TI  - Optimisation and use of water-in-oil MEEKC in pharmaceutical analysis.
AB  - Water-in-oil microemulsion electrokinetic chromatography has been applied to the
      separation of a range of acids, bases and neutrals and is especially suitable for
      very water-insoluble drug compounds. A number of operating parameters were
      evaluated. An optimised set of operating conditions allowed separation of a range
      of pharmaceutical formulations containing water-insoluble compounds. A number of
      novel applications for W/O microemulsions were developed and ability to quantify
      drug contents in tablets and a cream was shown with good precision, detector
      linearity and accuracy. Comparison of obtained data with those determined from a
      HPLC method showed acceptable agreement.

PMID- 15862662
TI  - High-resolution method for regulatory control of Echinacea species in
      Nutraceuticals by CD-MEKC.
AB  - One problem in the international regulatory control of Echinacea, a therapeutic
      Nutraceutical, is recognition of caffeoyl solutes and alkamides in different
      products. Cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC)
      has been applied to Echinacea spp. in combination with pattern recognition of
      some caffeoyl solutes. A novel metric based on relative migration time (RMT) data
      has been developed in CE to address the problem of variable reported migration
      time. The CD-MEKC method of Gotti's group using hydroxypropyl-beta-cyclodexrin
      (HP-beta-CD; 100 mM) with sodium dodecyl sulphate (SDS; 110 mM), in a triacid
      background electrolyte (10 mM, pH 8) under 19 kV was adapted to identify two key
      hydrophilic solutes: chlorogenic acid and cichoric acid present in all commercial
      products. Two internal markers were taken as reference points to calculate the
      RMT of any target peak: RMT=t(m (target))/t(m (marker)). The RMT method was
      robust to temperature change from 20 to 40 degrees C, but sensitive to pH. The
      lateral shift and reproducibility of the target peak t(m (target)) were
      significantly reduced by this novel transformation. In the worst cases migration
      time variability ranged up to 12% (n=6); the RMT algorithm reduced this to less
      than 1%. In general, the RMT transformation reduced the variability of migration
      time data by a factor of 2-5. For systematic comparison of electrophoretic
      profiles for test sample and standard, a new pattern recognition algorithm
      permits sequential peak-by-peak comparison using specified segments of the
      electropherograms for comparison of test and Echinacea purpurea (root product) as
      a standard. This algorithm was capable of rapidly characterising the similarity
      of target peaks in a test sample relative to those in the reference standard.
      Combination of the RMT algorithm and pattern recognition in CE is expected to
      offer a robust approach to international regulatory characterisation and control
      of Nutraceuticals.

PMID- 15862663
TI  - Automated system for release studies of salicylic acid based on a SIA method.
AB  - The aim of this work was to describe a fully automated system for the in vitro
      release testing of semisolid dosage forms based on SIA technique. The system was
      tested for monitoring release profiles of different ointments containing 3% of
      salicylic acid (Belosalic, Diprosalic, Triamcinolone S). The native fluorescence
      of salicylic acid was used for fluorimetric detection. Phosphate buffer pH 7.4
      was the receptor medium; samples were taken at 10 min intervals during 6 h of the
      release test; and each test was followed by calibration with five standard
      solutions. The linear calibration range was 0.05-10 microg ml(-1) (r = 0.9996,
      six standards); the maximal SIA sample throughput for this system was 120 h(-1),
      sample volume being 50 microl and flow rate 50 microl s(-1). The detection limit
      for salicylic acid was 0.01 microg ml(-1).

PMID- 15862664
TI  - Development and validation of HPLC method for determination of indomethacin and
      its two degradation products in topical gel.
AB  - Indomethacin forms by decomposition two degradation products: 4-chlorobenzoic
      acid and 5-methoxy-2-methylindoleacetic acid. They have to be monitored together
      with an active substance both during manufacturing process and storage of
      pharmaceuticals. European Pharmacopoeia (Ph. Eur. 4) describes titration method
      for determination of indomethacin, which is not very convenient in this case for
      practical use. Therefore, high performance liquid chromatography is the method-of
      choice enabling determination of active substance and its degradation products
      during one-step procedure simultaneously and automatically. We have developed a
      fast, simple and fully automated analytical method for determination of
      indomethacin and its two impurities in pharmaceutical preparation using HPLC with
      UV detection. Various stationary phases were tested, especially new types of
      Zorbax columns made by Agilent. While the conventional C18 stationary phases were
      not convenient enough to achieve quick and reliable separation, Zorbax-Phenyl
      analytical column (75 mm x 4.6 mm, 3.5 microm) enables separation of indomethacin
      and its two degradation products during 7.5 min. Chromatography was performed
      using isocratic elution with binary mobile phase composed of acetonitrile and
      0.2% phosphoric acid (50:50, v/v) at flow rate 0.6 ml/min. Even faster separation
      of standards was obtained with analytical column Zorbax SB-CN (150 mm x 4.6 mm, 5
      microm). The separation was effected with mobile phase of the same composition,
      only the flow rate was increased to 1.2 ml/min. The analytical run was shortened
      to 5 min. Both methods use detection wavelength 237 nm and both can use either
      ketoprofen or flurbiprofen as internal standard for quantitation. The first
      method was finally chosen for validation because of the occurrence of placebo
      interferences in the case of using Zorbax SB-CN. System suitability parameters
      and validation parameters including method precision, accuracy, linearity,
      selectivity and robustness were set up. Afterwards, the method was successfully
      applied for the practical determination of indomethacin and its degradation
      products in a topical gel and for compound degradation control during stability
      studies.

PMID- 15862665
TI  - Quantitative analysis of amorphous content of lactose using CCD-Raman
      spectroscopy.
AB  - A Raman spectroscopy method was developed for the quantification of the amorphous
      content of lactose. Both physical mixtures and spray-dried samples were used and
      the results were compared with the IMC determinations. Sample inhomogeneities
      were averaged out by collecting multiple spectra from each sample, and the total
      measurement time remained below 10 min due to the high sensitivity of the CCD
      Raman spectrometer used in the measurements. The obtained calibration error (SEC)
      for the physical mixtures was 1.3% (w/w) in the 0-100% amorphous content range
      and was reduced to 0.2% (w/w) in the 0-10% range of more practical interest. The
      crystallization heat values of the spray-dried samples showed a linear
      correlation with the Raman quantifications in the amorphous content range of 0
      80%, but saturated over the 80% concentration. This finding suggests a reference
      value of ca. 60 J/g for the spray-dried samples, instead of the crystallization
      heat of amorphous lactose (ca. 50 J/g) valid in the IMC determinations of
      physical mixtures.

PMID- 15862666
TI  - Determination of local anaesthetics and their impurities in pharmaceutical
      preparations using HPLC method with amperometric detection.
AB  - A method for the determination of local anaesthetics and their impurities--2,6
      dimethylaniline and o-toluidine--by high-performance liquid chromatographic
      method with amperometric detection has been developed. The analysis was performed
      in an isocratic mode on a reversed phase Luna column 5 microm C-18 (100 mm x 4.6
      mm). A mobile phase [0.01 mol l(-1) Tris buffer of pH 7.9:acetonitrile (45:55)]
      was selected for the separation and determination of studied anaesthetics and
      their impurities. Chromatograms were recorded for 500 s by means of an
      amperometric detector at a potential of +1.0 V of the glassy carbon electrode
      versus the reference electrode Ag/AgCl. The proposed liquid chromatographic
      method was successfully applied to the analysis of commercially available
      pharmaceutical preparations. The limit of the detection for 2,6-dimethylaniline
      and o-toluidine was 0.8 ng ml(-1). The limit of quantitation, considering a
      signal to noise ratio was 1.5 ng ml(-1). The method developed in this study is
      sensitive and selective and can be applied to routine studies of pharmaceuticals
      in the form of cream and injection.

PMID- 15862667
TI  - Methotrexate determination in pharmaceuticals by enantioselective HPLC.
AB  - A simple, sensitive and selective high performance liquid chromatographic method
      with UV detection for the chiral separation of racemic methotrexate (rac-Mtx) and
      enantiomeric purity of L-methotrexate in pharmaceutical formulations was
      developed and validated. The chiral separation was optimized studying both the
      nature of the stationary phase by using Chirobiotic T, Chiracel OJ and human
      serum albumin columns and the effect of the mobile phase composition. The best
      results in terms of enantioresolution and enantioselectivity were achieved with a
      polar organic mobile phase on Chirobiotic T stationary phase. Essential steps in
      method validation such as precision, accuracy, suitability and stability were
      studied according to ICH guidelines. At wavelength 303 nm, the limit of detection
      (S/N=3) was found to be 0.9 microg/ml for rac-Mtx. The separation of D-Mtx at
      0.2% (w/w) level (as limit of quantitation) from the main drug L-Mtx was
      successfully obtained with 1.72 enantioresolution value. Enantiomeric purity of L
      Mtx was determined in pharmaceutical formulations (tablets and injections) with
      inter- and intra-days relative standard deviation < or = 1.6%. Under the
      validated stereoselective HPLC conditions for methotrexate, folic acid was also
      analysed.

PMID- 15862668
TI  - Laser diffraction for standardization of heterogeneous pharmaceutical
      preparations.
AB  - A new quantitative method for standardization of heterogeneous pharmaceutical
      preparations and their quality control during storage based on laser diffraction
      is proposed. A series of pharmaceutical dosage forms--suspensions, emulsions,
      tinctures, decoctions, cell preparations and others, are heterogeneous medicines.
      In some cases disperse phase can be formed during storage as a result of layering
      (L1/L2) or precipitation (S/L). Laser diffraction method proposed in this study
      can be used for standardization and quality control of medicines.

PMID- 15862669
TI  - Particle size analysis of some water/oil/water multiple emulsions.
AB  - Particle size analysis gives useful information about the structure and stability
      of multiple emulsions, which are important characteristics of these systems. It
      also enables the observation of the growth process of particles dispersed in
      multiple emulsions, accordingly, the evolution of their dimension in time. The
      size of multiple particles in the seven water/oil/water (W/O/W) emulsions was
      determined by measuring the particles size observed during the microscopic
      examination. In order to describe the distribution of the size of multiple
      particles, the value of two parameters that define the particle size was
      calculated: the arithmetical mean diameter and the median diameter. The results
      of the particle size analysis in the seven multiple emulsions W/O/W studied are
      presented as histograms of the distribution density immediately, 1 and 3 months
      after the preparation of each emulsion, as well as by establishing the mean and
      the median diameter of particles. The comparative study of the distribution
      histograms and of the mean and median diameters of W/O/W multiple particles
      indicates that the prepared emulsions are fine and very fine dispersions, stable,
      and presenting a growth of the abovementioned diameters during the study.

PMID- 15862670
TI  - Standardization of marketed Kumariasava--an Ayurvedic Aloe vera product.
AB  - Kumariasava is a marketed ayurvedic formulation containing Aloe vera as one of
      the main ingredients. Present study aims to standardize Kumariasava based upon
      chromatographic and spectral studies. Various extracts of Kumariasava have been
      prepared and evaluated. Chloroform extract indicated presence of three well
      resolved fluorescent components. Spectral data of these three fractions (III-V)
      have been reported as a valuable analytical tool for routine standardization of
      Kumariasava. Fraction V indicated presence of anthraquinones, which is reported
      as the main constituent of aloe, namely aloin. Hence, isolation and evaluation of
      aloin has been undertaken. Aloin can be used as possible marker compound for
      standardization of Kumariasava.

PMID- 15862671
TI  - Preparation of a diclofenac potentiometric sensor and its application to
      pharmaceutical analysis and to drug recovery from biological fluids.
AB  - A novel diclofenac ion-selective electrode is prepared, characterized and used in
      pharmaceutical analysis. The diclofenac complex with hexadecylpyridinium bromide
      is obtained in situ by soaking the PVC-membranes in a 1x10(-2) M diclofenac
      solution. Among four different solvent mediators tested, dibutyl phthalate (DBP)
      exhibited a proper behavior including Nernstian slope of the calibration curve,
      fast response time and good reproducibility of the emf values. The electrode
      exhibits a Nernstian slope of -59+/-1 mV decade(-1) for diclofenac in the
      concentration range 1.0x10(-5) to 1.0x10(-2) M with a limit of detection of
      4.0x10(-6) M. The electrode displays a good selectivity for diclofenac with
      respect to a number of common inorganic and organic species. It can be used in a
      pH range of 6.0-9.0. The membrane sensor was successfully applied to the
      determination of diclofenac in its tablets as well as for its recovery from blood
      serum and urine samples.

PMID- 15862672
TI  - Thermal analysis study of the interactions between acetaminophen and excipients
      in solid dosage forms and in some binary mixtures.
AB  - Thermogravimetry (TG) and differential scanning calorimetry (DSC) were used to
      assess the compatibility between acetaminophen (Ac) and some excipients
      (polyvinylpyrrolidone (P), magnesium stearate (M), citric acid (C), aspartame
      (As), mannitol (Mn), cellulose (Cll) and starch (S)) in several of the more
      commercially available pharmaceutical formulations and in solid binary mixtures.
      The present study compared thermodynamic data on acetaminophen melting and
      vaporization processes of pure acetaminophen with those found for several solid
      mixtures and in some commercially available acetaminophen-based dosage forms.
      Appreciable modifications occur only for solid mixtures with high content of
      excipient. Acetaminophen-based dosage forms and its solid binary mixtures usually
      show "additivity" of calorimetric peaks number of pure components in their
      calorimetric curve profiles, thus revealing a good thermoanalytical compatibility
      between acetaminophen and the excipients examined, except for samples containing
      appreciable content of mannitol.

PMID- 15862673
TI  - Evaluation of in vitro effects of natural substances of plant origin using a
      model of protein glycoxidation.
AB  - In an in vitro model with purified porcine aspartate aminotransferase (AST, EC
      2.6.1.1) as the protein, the effects of phenolic antioxidants of plant origin
      (arbutin, methylarbutin, ferulic and isoferulic acids, o-coumaric and p-coumaric
      acids, quinic acid), flavonoids (baicalin and baicalein), and of hydroxycitric
      acid (HCA) at 0.5-50 mM concentration on the enzyme activities and on its
      glycation by 50 mM D-fructose as the glycating agent were studied. During
      incubation with AST at 37 degrees C up to 24 days, fructose alone decreased AST
      activities as a result of protein glycation. In the absence of fructose, 50 mM
      phenolic compounds gradually decreased AST activity, while no or a weak effect of
      individual compounds was found at 3 mM concentration. A direct negative effect on
      AST was pronounced with ferulic acid. On the other hand, beneficial influences of
      phenolic compounds on glycation of AST by fructose were found mostly at 3 mM
      concentration. Effects on glycation were vague at 50 mM concentration, probably
      due to a combination of direct negative influences and antiglycation effects of
      individual compounds. No effect, neither positive nor negative, on AST activity
      and protein glycation, was found with quinic acid. The flavonoid baicalin and its
      aglycon baicalein rapidly decreased the in vitro activity of the enzyme in all
      concentrations used (0.5-3 mM), and no beneficial effects of the compounds on
      glycation of the enzyme by fructose were found. The influence of HCA on glycation
      was concentration-depended, ranging from beneficial inhibition of glycation at
      2.5 mM concentration to a strong decrease in AST activity at 10 mM HCA. Both the
      beneficial and undesirable effects of natural antioxidants should be considered
      in case they are used as antiglycation factors. The results obtained can
      contribute to the evaluation of quality of various generally recommended
      antioxidants.

PMID- 15862674
TI  - Analytical method for appreciation of garlic therapeutic potential and for
      validation of a new formulation.
AB  - The consumption of garlic reduces the risk of cardiovascular disease and cancer,
      S-allylcysteine sulfoxide (alliin), allicin (DATi), diallyl disulfide (DADS), S
      allylcysteine (SAC) and several storage dipeptides are the organo-sulphur
      compounds (OSC) involved in the protective mechanism of garlic against
      cardiovascular disorders and carcinogenesis. Thus it is very interesting to
      quantify simultaneously all these compounds in different garlic powders obtained
      in several cultural conditions. The quantification of OSC by a new ion-pair HPLC
      method allowed showing the general sulphur-dependence positive effect of garlic
      on cardiovascular disorder and carcinogenesis and the variable specific activity
      of each implicated OSC. The screening of 11 garlic tablets proposed on the market
      showed the variability and particularly the differential instability of each OSC.
      From these results, a new garlic tablet was realised and each step was controlled
      by this method. This analytical method proved to be a very powerful tool for the
      understanding of the garlic protective mechanism against cancer and
      cardiovascular diseases and the development and quality control of garlic
      tablets.

PMID- 15862675
TI  - Fast determination of colchicine by TLC-densitometry from pharmaceuticals and
      vegetal extracts.
AB  - Colchicine, (S)-N-(5,6,7,9-tetrahydro-1,2,3,10-tetramethoxy-9-oxobenzo-(a(
      heptalen-7-yl)-acetamide, is the main alkaloid contained in Colchicum autumnale
      (meadow saffron). There are known colorimetric, spectrophotometric, volumetric,
      potentiometric, voltametric, gravimetric and various chromatographic methods for
      quantitative determination of colchicine, each of them presenting a series of
      advantages and disadvantages. As an alternative, we proposed the use of a
      densitometric determination for colchicine allowing the determination of this
      alkaloid from pharmaceutical products, as well from seeds of meadow saffron. The
      total alkaloid extract was separated by Thin-Layer Chromatography using Silicagel
      60F(254) layers and a mixture of chloroform:acetone:diethylamine (5:4:1) as
      mobile phase. The same conditions were used for the determination from
      pharmaceutical products. Densitometric measurements were carried out at the
      absorption maximum (350 nm) of colchicine, the determinations being made by
      reflectance and by fluorescence. The peaks were optimized regarding to their area
      and shape by varying four scanning parameters (slit width and height, number of
      measurements and scanning speed). We established the calibration plot using pure
      colchicine in the range 50-600 ng mL(-1). The proposed method could be widely
      used in the pharmaceutical industry for the quick and accurate quantitative
      determination of colchicine because it eliminates the interferences given by
      other bioactive or degradation compounds. The method was characterized by
      validation parameters (linearity, accuracy, fidelity, sensitivity) and it was
      established its performances in comparison with an HPLC method and an official
      quantitative determination from the Romanian Pharmacopoeia X edition
      respectively.

PMID- 15862676
TI  - HPLC-DAD and LC-ESI-MS analysis of doxycycline and related impurities in doxipan
      mix, a medicated premix for incorporation in medicated feedstuff.
AB  - HPLC-DAD and LC-ESI-MS methods have been developed for the analysis of
      doxycycline (DOX), including the identification of the related impurities
      metacycline (MTC) and 6-epidoxycycline (EDOX) and its determination in a
      medicated premix. The chromatographic separations have been performed on Luna C18
      stationary phase and on Synergi (4 microm) Polar-RP 80A, using both acidic (pH
      2.5) and basic (pH 8.0) mobile phases. The Synergi Polar-RP column, in
      combination with a mobile phase of oxalic acid (0.02 M; pH 2.5)-acetonitrile
      82:18 (v/v), allowed the complete separation of MTC, EDOX and DOX. The same
      separation was also obtained using Luna C18 stationary phase with a pH 8 mobile
      phase. Application of a LC-ESI-MS system and MS/MS analysis, using both positive
      and negative polarity, allowed the peak identity to be confirmed. A method based
      on Luna C18 column and UV detection at 346 nm was validated for the determination
      of DOX in a medicated premix for incorporation in medicated feedstuff.

PMID- 15862677
TI  - Interaction of naproxen with ionic cyclodextrins in aqueous solution and in the
      solid state.
AB  - The possible role of the cyclodextrin charge in the interaction with an acidic
      drug such as naproxen (pKa 4.8) has been evaluated. Sulfobutylether-beta
      cyclodextrin (SBE-betaCyd) and trimethylammonium-beta-cyclodextrin (TMA-betaCyd)
      were selected as, respectively, anionically and cationically charged carriers and
      their performance was compared with that of the parent beta-cyclodextrin
      (betaCyd) and of its methyl-derivative (Me betaCyd) previously found as the best
      partner for the drug. Interactions in solution were investigated by phase
      solubility, fluorescence and circular dichroism analyses. Equimolar drug-carrier
      products prepared by different techniques (blending, cogrinding, sealed-heating,
      colyophilization) were characterized by differential scanning calorimetry and X
      ray powder diffractometry and tested for drug dissolution properties. Anionic
      charges of SBE-betaCyd did not negatively influence interactions in unbuffered
      aqueous solutions (pH approximately 5) with the acidic drug. In fact, it was a
      very effective carrier, exhibiting solubilizing and complexing properties
      considerably better than the parent betaCyd and comparable to those of Me
      betaCyd. On the contrary, the positive charges of TMA-betaCyd did not favour
      interactions with the counter-ionic drug (despite the presence of about 60%
      ionised drug) and it was less efficacious also than native betaCyd. Therefore,
      the role of the Cyd charge on the complexing and solubilizing properties towards
      naproxen was not important whereas other factors, such as steric hindrance
      effects and favourable hydrophobic interactions were significant in determining
      the drug affinity for the Cyd inclusion. Solid state studies evidenced similar
      amorphizing properties of both charged Cyds towards naproxen. On the other hand,
      dissolution tests, in agreement with solution studies, showed that all products
      with SBE-betaCyd exhibited significantly better dissolution properties than the
      corresponding ones with TMA-betaCyd. A clear influence of the preparation method
      of drug-Cyd solid systems on the performance of the end product was also
      observed. Colyophilization was the most effective technique, followed by the
      cogrinding one. Colyophilized product with SBE-betaCyd allowed a 10-times
      increase in drug dissolution efficiency (D.E.) (with respect to the five-times
      increase obtained with the corresponding coground product) and a reduction of
      t(50%) from about 60 min (for the coground product) to less than 2 min.

PMID- 15862678
TI  - Determination of stability constant values of flurbiprofen-cyclodextrin complexes
      using different techniques.
AB  - Three new experimental approaches for calculating the stability constant (K(st))
      of complexes of flurbiprofen with natural beta-cyclodextrin (betaCyd) and the
      hydroxyethyl- (HEbetaCyd) and the methyl- (Me betaCyd) derivatives were tested
      and compared to the classic phase-solubility procedure: (a) the membrane
      permeation technique through a lipophilic synthetic membrane permeable to the
      drug but not to the Cyd molecules, by analysing the permeation profiles with a
      non-linear least-squares method; (b) the affinity capillary electrophoresis (ACE)
      technique, where K(st) were calculated from the relationship between Cyd
      concentration in solution and drug electrophoretic mobility, using three
      different linear plotting methods; (c) the molecular modeling technique, based on
      the relationship between the docking energies and the experimental K(st) values.
      The study allowed evaluation of the advantages and limits of each examined
      method, providing a useful guide for the choice of the most suitable one
      depending on the kind of host-guest system to be investigated. The K(st) values
      obtained with the various techniques were rather different, probably due to the
      very different experimental conditions required by each one. However, all the
      methods indicated the methyl-derivative as the most powerful complexing agent for
      the drug, showing the general trend: K(st)(Me
      betaCyd)>>K(st)(HEbetaCyd)>K(st)(betaCyd). Only in the case of the ACE method was
      an inversion of the trend found between HEbetaCyd and betaCyd; this was probably
      due to the lower molecular weight of the natural Cyd, which, in this case, became
      more important in determining the complex electrophoretic mobility than the
      different affinity of the drug for these two Cyds.

PMID- 15862679
TI  - Novel composite poly(4-vinylpyridine)/polypropylene membranes with recognition
      properties for (S)-naproxen.
AB  - In the last few years, molecular imprinting technology has entered in different
      fields of chemistry, biochemistry, biotechnology and medicine. The technique
      allows us to introduce the molecular memory of the substrate to be recognized in
      a polymeric material during its preparation. In the present paper, molecularly
      imprinted enantioselective polymer membranes were prepared by photo
      copolymerization of commercial polypropylene membranes with the functional
      monomer 4-vinylpyridine. The (S)-naproxen was used as a template molecule.
      Enantioselectivity studies in a dead-end filtration system showed the recognition
      properties of the imprinted membranes, which exhibited a selective transport of
      the (S)-enantiomer.

PMID- 15862680
TI  - The 6-derivative of beta-cyclodextrin with succinic acid: a new chiral selector
      for CD-EKC.
AB  - 6-O-Succinil-beta-cyclodextrin (CDsuc6) was synthesized with very good yield by
      one pot synthesis and characterized by NMR spectroscopy and ESI-MS. It was used
      as a chiral selector in capillary electrophoresis to resolve catecholamine
      racemates, namely norepinephrine, epinephrine, terbutaline and norphenilephrine.
      The CE experiments at pH 5.6 show very promising selector ability by 6-O-succinil
      beta-cyclodextrin for the chiral recognition of all the catecholamines tested,
      while at pH 9.2, only racemic terbutaline was successfully separated.

PMID- 15862681
TI  - Assay of stability, free and total concentration of chlorhexidine in saliva by
      solid phase microextraction.
AB  - This paper presents the development and application of a solid phase
      microextraction method for the full investigation of chlorhexidine interaction
      with saliva during a pharmacokinetic study: chemical stability, binding to
      proteins, free concentration, total concentration and kinetics of elimination
      after oral administration. Only 0.1 mL sample were needed for each time point and
      the concentration of salivary proteins was determined as well. It was shown that
      chlorhexidine remained stable in the oral cavity for at least 9 h and high
      concentrations of the drug (2 microg/mL total) were still present even 8 h after
      mouthrinsing. Supplementary facts were uncovered: while the total concentration
      followed first-order elimination kinetics, the free concentration remained almost
      constant for several hours; this showed that the oral cavity acted like a
      reservoir that slowly released the drug. It was also revealed that following oral
      administration of chlorhexidine, the normal composition of saliva changed for a
      few hours, probably as a physiological response to the bitter taste of the
      medicine. The method had a wide linear range (0.1-40 microg/mL free
      chlorhexidine) that was perfectly suitable for the study of chlorhexidine
      retention in the oral cavity. Separation and quantitation were achieved by liquid
      chromatography coupled to mass spectrometry; no interference from endogenous
      compounds was observed. This selective and sensitive solid-phase microextraction
      (SPME) approach for monitoring the free and total concentration of a drug, as
      well as the concentration of proteins that bind that drug, should prove to be
      more useful for pharmacokinetic studies than classic methods that only provide
      the total concentration as a final result.

PMID- 15862682
TI  - Determination of thiamine and its phosphorylated forms in human plasma,
      erythrocytes and urine by HPLC and fluorescence detection: a preliminary study on
      cancer patients.
AB  - In man, neurotoxicity associated to ifosfamide treatment can be reversed by
      intravenous thiamine administration. Trying to explain this clinical finding, we
      decided to study possible changes in thiamine availability and activation in
      patients exposed to ifosfamide. Free thiamine and its phosphate esters levels
      were measured in plasma, erythrocytes and urine by an ion-pair HPLC method with
      pre-column derivatization, which allowed separation of the fluorescent compounds
      in less than 10 min. The method was validated by linearity, sensitivity and
      reproducibility studies, whose values met the demands for bioanalytical assays.
      This method was applied to assess thiamine status in cancer patients exposed to
      ifosfamide therapy for advanced disease.

PMID- 15862683
TI  - Screening of anabolic steroids in horse urine by liquid chromatography-tandem
      mass spectrometry.
AB  - Anabolic steroids have the capability of improving athletic performance and are
      banned substances in the Olympic games as well as in horseracing and equestrian
      competitions. The control of their abuse in racehorses is traditionally performed
      by detecting the presence of anabolic steroids and/or their metabolite(s) in
      urine samples using gas chromatography-mass spectrometry (GC-MS). However, this
      approach usually requires tedious sample processing and chemical derivatisation
      steps and could be very insensitive in detecting certain steroids. This paper
      describes a high performance liquid chromatography-tandem mass spectrometry (HPLC
      MS-MS) method for the detection of anabolic steroids that are poorly covered by
      GC-MS. Enzyme-treated urine was processed by solid-phase extraction (SPE) using a
      Bond Elut Certify cartridge, followed by a base wash for further cleanup.
      Separation of the steroids was carried out on a reversed-phase DB-8 column using
      0.1% acetic acid and methanol as the mobile phase in a gradient elution
      programme. The mass spectrometer for the detection of the steroids was operated
      in the positive electrospray ionisation (ESI) mode with multiple reaction
      monitoring (MRM). Urine samples fortified with 15 anabolic steroids (namely,
      androstadienone, 1-androstenedione, bolasterone, boldione, 4-estrenedione,
      gestrinone, methandrostenolone, methenolone, 17alpha-methyltestosterone,
      norbolethone, normethandrolone, oxandrolone, stenbolone, trenbolone and
      turinabol) at low ng/mL levels were consistently detected. No significant matrix
      interference was observed at the retention times of the targeted ion masses in
      blank urine samples. The method specificity, sensitivity, precision, recoveries,
      and the performance of the enzyme hydrolysis step were evaluated. The successful
      application of the method to analyse methenolone acetate administration urine
      samples demonstrated that the method could be effective in detecting anabolic
      steroids and their metabolites in horse urine.

PMID- 15862684
TI  - High-throughput determination of ultra-low concentrations of LAG078, a lipid
      modulator, in human plasma.
AB  - A high throughput method with ultra-low level quantification limit (10 pg/ml) was
      developed and validated for the quantitative determination of LAG078, a lipid
      modulator, in human plasma to support clinical studies employing low doses of the
      compound. The method consisted of reverse phase chromatographic separation of the
      analyte from plasma extract followed by electrospray ionization (ESI) in the
      negative ion mode and tandem mass spectrometry in the multiple reaction
      monitoring mode (MRM). Extraction was performed using a combination of protein
      precipitation and liquid-liquid extraction in the 96-well plate format to
      increase the throughput of the method. Optimised chromatographic separation in a
      short and high-resolution column (50 mm x 2.0 mm i.d., 3 microm particle size)
      coupled with MRM mode of detection yielded clean chromatograms with minimal
      signal suppression. The standard curve was linear (r=0.996) within the
      concentration range of 0.01 (lower limit of quantification) to 50 ng/ml using 0.5
      ml of human plasma. The accuracy of the method varied from 95-101% with a
      precision (CV) of 5.29-13.2% over the concentration range. The method was simple
      and rapid.

PMID- 15862685
TI  - Use of chiral liquid chromatography for the evaluation of stereospecificity in
      the carbonyl reduction of potential benzo[c]fluorene antineoplastics benfluron
      and dimefluron in various species.
AB  - Benfluron (B) [5-(2-dimethylaminoethoxy)-7H-benzo[c]fluorene-7-one hydrochloride]
      is a potential antineoplastic agent. In the organism, B undergoes a rapid phase I
      biotransformation through oxidative and reductive metabolic pathways. The
      carbonyl reduction of B leads to reduced benfluron, red-B, this is one of the
      principal pathways for the deactivation of this compound. The structure of B was
      modified to suppress its rapid deactivation via the carbonyl reduction on C7.
      Dimefluron, D (3,9-dimethoxy-benfluron) is one of the derivatives of B, in which
      an alternative metabolic pathway (O-desmethylation) prevails over the carbonyl
      reduction. The goal of this study was to develop HPLC methods enabling chiral
      separations of the red-B and -D enantiomers. The separation of red-B enantiomers
      was successful done on a Chiralcel OD-R column (250 mm x 4.6 mm ID, 5 microm)
      using a mobile phase acetonitrile-1 M NaClO4 (40:60, v/v). Another mobile phase,
      methanol-1 M NaClO4 (75:25, v/v), had to be employed for the sufficient
      resolution of red-D enantiomers. Flow rate was 0.5 ml min(-1) in both cases. Red
      B was detected at 340 nm, red-D at 370 nm. The above chiral HPLC methods were
      used for the study of the biotransformation of B and D in the microsomal
      fractions of liver homogenates prepared from various species (rat, rabbit, pig,
      guinea pig, goat and human). The enantiospecificity of the respective carbonyl
      reductases was evaluated and discussed for both prochiral compounds, B and D.

PMID- 15862686
TI  - Disposition study of a new potential antineoplastic agent dimefluron in rats
      using high-performance liquid chromatography with ultraviolet and mass
      spectrometric detection.
AB  - The disposition of a new potential antineoplastic drug dimefluron after an oral
      administration to rats was investigated. Dimefluron, 3,9-dimethoxy-5-(2
      dimethylaminoethoxy)-7H-benzo[c]fluoren-7-one hydrochloride, was administered in
      a single oral dose (250 mg kg(-1) of body weight) in the form of an aqueous
      solution via a gastric probe. Dimefluron metabolites were being searched for in
      rat faeces. Synthetic standards of the expected phase I metabolites (the products
      of O- and N-desmethylation, N-oxidation and carbonyl reduction of dimefluron)
      were prepared and used together with dimefluron and internal standard in the
      development of two HPLC bioanalytical methods based on different separation
      principles. The first separation of dimefluron and the phase I metabolites was
      tested on a 250 mm x 4 mm chromatographic column with LiChrospher 60 RP-selectB 5
      microm (Merck) using an isocratic mobile phase containing 0.01 M nonylamine
      buffer (pH 7.4) and acetonitrile in the 1:2 ratio (v/v). The second separation
      was performed on a 250 mm x 4 mm chromatographic column Discovery HS F5, 5 microm
      (Supelco) using a linear gradient mode with the mobile phase containing
      acetonitrile and phosphate buffer (0.05 M KH2PO4, pH 3). The flow rate was 1 ml
      min(-1) in both cases. UV detection was performed in the dual wavelength mode,
      with 317 nm having been used for dimefluron and all 7H-benzo[c]fluoren-7-one
      metabolites, 367 nm for 7H-benzo[c]fluoren-7-ol metabolites. A higher homologue
      of dimefluron served as an internal standard. The identity of the dimefluron
      metabolites in biological samples was confirmed using HPLC-MS experiments. The
      elimination study showed that the concentration maximum for dimefluron and its
      metabolites in rat faeces was reached 48 h after the administration of the parent
      drug. O-Desmethylated derivatives of dimefluron prevailed among the phase I
      metabolites.

PMID- 15862687
TI  - A selective and rapid method for the quantification of captopril in human plasma
      using liquid chromatography/selected reaction monitoring mass spectrometry.
AB  - A specific hyphenated high performance liquid chromatography-mass spectrometric
      (LC-MS/MS) assay was developed for the determination of captopril in plasma. The
      drug was extracted from plasma using liquid-liquid extraction with a mixture of
      diethylether:dichloromethane. After the addition of the internal standard,
      samples were applied to a prepacked C8 Waters Symmetry column. The ion trap MS/MS
      detector was equipped with electrospray ionization (ESI) source operating in the
      positive ion mode. Drug determination was accomplished monitoring captopril at
      molecular ion m/z 218 and MS/MS (daughter) at m/z 171.6. The method was applied
      to captopril determination in human plasma after the administration of captopril
      50 mg tablets to healthy volunteers who have participated in a pharmacokinetic
      study. The method was proved to be specific and precise by testing six different
      plasma batches. Linearity was established for the range of concentrations 25-3000
      ng/ml with a regression factor of 0.9995. Intra-day accuracy ranged from 90.16 to
      96.18%, while the intra-day precision ranged from 2.60 to 9.66% at the
      concentrations of 75, 1440 and 2500 ng/ml. Inter-day precision of the method
      ranged from 5.04 to 10.10%. This validated method of analysis was successfully
      applied to human plasma analyses after the administration of a single dose of 50
      mg captopril tablets to healthy volunteers.

PMID- 15862688
TI  - Development and validation of a bioanalytical method using automated solid-phase
      extraction and LC-UV for the simultaneous determination of lumefantrine and its
      desbutyl metabolite in plasma.
AB  - A bioanalytical method for the determination of lumefantrine (LF) and its
      metabolite desbutyl-lumefantrine (DLF) in plasma by solid-phase extraction (SPE)
      and liquid chromatography has been developed. Plasma proteins were precipitated
      with acetonitrile:acetic acid (99:1, v/v) containing a DLF analogue internal
      standard before being loaded onto a octylsilica (3 M Empore) SPE column. Two
      different DLF analogues were evaluated as internal standards. The compounds were
      analysed by liquid chromatography UV detection on a SB-CN (250 mm x 4.6 mm)
      column with a mobile phase containing acetonitrile-sodium phosphate buffer pH
      (2.0; 0.1 M) (55:45, v/v) and sodium perchlorate 0.05 M. Different SPE columns
      were evaluated during method development to optimise reproducibility and recovery
      for LF, DLF and the two different DLF analogues. The within-day precisions for LF
      were 6.6 and 2.1% at 0.042 and 8.02 microg/mL, respectively, and for DLF 4.5 and
      1.5% at 0.039 and 0.777 microg/mL, respectively. The between-day precisions for
      LF were 12.0 and 2.9% at 0.042 and 8.02 microg/mL, respectively, while for DLF
      0.7 and 1.2% at 0.039 and 0.777 microg/mL, respectively. The limit of
      quantification was 0.024 and 0.021 microg/mL for LF and DLF, respectively.
      Different amounts of lipids in plasma did not affect the absolute recovery of LF
      or DLF.

PMID- 15862689
TI  - LC-MS determination of MPTP at sub-ppm level in pethidine hydrochloride.
AB  - An HPLC-MS with electrospray ionisation method for the determination of MPTP at
      sub-ppm level in pethidine hydrochloride has been developed and validated.
      Ionisation is performed by positive-ion electrospray and the quadrupole filter
      mass spectrometer is operated in the single ion recording mode. Chromatographic
      separation was achieved in gradient elution using a symmetry C18, 5 microm, 150
      mm x 2.1 mm i.d. The mobile phase comprised water containing 0.1% formic acid
      (v/v) and acetonitrile containing 0.1% formic acid (v/v). The method showed to be
      linear in the range between 0.2 and 2.2 ng/ml, the estimated LOD was lower than
      0.1 ng/ml and the LOQ was lower than 0.2 ng/ml.

PMID- 15862690
TI  - Determination of fentanyl in human plasma and fentanyl and norfentanyl in human
      urine using LC-MS/MS.
AB  - Fentanyl, a potent analgesic drug, has traditionally been used intravenously in
      surgical or diagnostic operations. Formulations with fentanyl in oral
      transmucosal delivery system and in transdermal depot-patch have also been
      developed against breakthrough pain in cancer patients. In this report, LC-MS/MS
      methods to determine fentanyl in human plasma as well as fentanyl and its main
      metabolite, norfentanyl, in human urine are presented together with validation
      data. The validation ranges were 0.020-10.0 and 0.100-50.0 ng/ml for fentanyl in
      plasma and urine, respectively, and 0.102-153 ng/ml for norfentanyl in urine.
      Liquid-liquid extraction of the compounds fentanyl, norfentanyl and the
      deuterated internal standards, fentanyl-d5 and norfentanyl-d5 from the matrixes
      was applied and separation was performed on a reversed phase YMC Pro C18-column
      followed by MS/MS detection with electrospray in positive mode. The inter-assay
      precision (CV%) was better than 4.8% for fentanyl in plasma and 6.2% and 4.7% for
      fentanyl and norfentanyl, respectively, in urine. The ruggedness of the methods,
      selectivity, recovery, effect of dilution and long-term stability of the analytes
      in plasma and urine were investigated. Effect of haemolysis and stability of
      fentanyl in blood samples were also studied. The methods have been applied for
      the determination of fentanyl in plasma samples and fentanyl/norfentanyl in urine
      samples taken for pharmacokinetic evaluation after a single intra-venous (i.v.)
      dose of 75 microg fentanyl.

PMID- 15862691
TI  - Improvements in europium sensitized fluorimetric determination of demeclocycline
      and methacycline.
AB  - Demeclocycline (DM) and methacycline (MT) have been determined by europium
      sensitized fluorescence, using EDTA as co-ligand and cetyltrimethylammonium
      chloride as surfactant. The methods have been developed in slightly alkaline
      solutions, with the formation of a new chelate where the lanthanide ion is bound
      to the beta-diketone group. Calibration graphs between 0.01 and 0.1 microg mL(-1)
      have been obtained for DM and MT determination. Both methods have been applied to
      the determination of these tetracyclines in serum samples with satisfactory
      recovery results.

PMID- 15862692
TI  - FTIR microscopy as a method for identification of bacterial and fungal
      infections.
AB  - Fourier-transform infrared (FTIR) microscopy is considered to be a comprehensive
      and sensitive method for detection of molecular changes in cells. The advantage
      of FTIR microspectroscopy over conventional FTIR spectroscopy is that it
      facilitates inspection of restricted regions of the examined sample. In the
      present study, we examined the potential of FTIR microscopy as an easy, rapid and
      reliable technique for discrimination between bacteria and fungi both of which
      are involved in various human and other animal infections. In many cases, there
      is no easy and rapid technique for identifying the cause of such infections
      whether it is bacteria, fungi or both. Knowing such information in a rapid way
      could be highly important for effective therapy. Our results proved detectable
      and significant spectral differences between bacterial and fungal samples.
      Representative peaks of bacteria and fungi appeared clearly in the spectra of a
      mixture of bacteria and fungi. It seems that this technique could be used for
      rapid discrimination between bacterial and fungal infections and contaminations.

PMID- 15862693
TI  - Validated specific HPLC method for determination of zidovudine during stability
      studies.
AB  - The objective of the current study was to develop a validated stability
      indicating assay method (SIAM) for zidovudine (3'-azido-3'-deoxythymidine) after
      subjecting it to forced decomposition under hydrolysis, oxidation, photolysis and
      thermal stress conditions. The drug decomposed under hydrolytic stress upon
      refluxing, and also on exposure to light. It was stable to oxidation and thermal
      stress. The same major decomposition product could be seen in all the decomposed
      solutions, which was identified as thymine through comparison with the standard.
      Separation of drug from major and minor degradation products was successfully
      achieved on a C-18 column utilising water-methanol in the ratio of 77:23. The
      detection wavelength was 265 nm. The method was validated and response was found
      to be linear in the drug concentration range of 25-500 microg ml(-1). The mean
      values (+/-R.S.D.) of slope and correlation coefficient were 21,859 (+/-0.213)
      and 0.9995 (+/-0.00578), respectively. The R.S.D. values for intra- and inter-day
      precision were <0.9 and <1.6%, respectively. The method was established to have
      sufficient intermediate precision as similar separation was achieved on another
      instrument handled by a different operator. The recovery of the drug from a
      mixture of degraded samples ranged between 100.6 and 100.9%. PDA peak purity test
      confirmed the specificity of the method. The method was also successful in
      analysis of drug in marketed tablets subjected to stability testing under
      accelerated conditions of temperature, humidity, and to thermal and photolytic
      stress.

PMID- 15862695
TI  - Determination of cationic surfactants as the preservatives in an oral solution
      and a cosmetic product by capillary electrophoresis.
AB  - In this study, a capillary electrophoresis method was developed for the
      determination of cationic surfactants, benzethonium and cetylpyridinium ions,
      which are commonly used as preservatives in various pharmaceutical and cosmetic
      products. Determination was performed in a fused-silica capillary using a mixed
      75 mmol/L phosphoric acid and 50% acetonitrile electrolyte at pH 2.5. Analysis of
      benzethonium and cetylpyridinium ions was achieved in around 5 min. Repeatability
      in migration times (R.S.D.%) for benzethonium and cetylpyridinium ions were 0.3.
      The calibration curves were linear from 0.0125 to 0.400 mmol/L for benzethonium
      ions and from 0.025 to 0.400 mmol/L for cetylpyridinium ions. The minimum
      detection limits (signal-to-noise ratio=3) are 1.47 and 4.30 microg/mL for
      benzethonium and cetylpyridinium ions, respectively. The method was applied to
      the analysis of benzethonium ion in a cosmetic product and cetylpyridinium ion in
      a mouthwash.

PMID- 15862694
TI  - Establishment of inherent stability of stavudine and development of a validated
      stability-indicating HPLC assay method.
AB  - The present study describes degradation of stavudine under different stress
      conditions (hydrolysis, oxidation, photolysis and thermal stress), and
      establishment of a stability-indicating reversed-phase HPLC assay method. The
      drug was found to hydrolyse in acidic, neutral and alkaline conditions and also
      under oxidative stress. The major degradation product formed under various
      conditions was thymine, as evidenced through comparison with the standard and
      spectral studies (NMR, IR and MS) on the isolated product. Separation of drug,
      thymine and another minor degradation product was successfully achieved on a C-18
      column utilising water-methanol in the ratio of 90:10. The detection wavelength
      was 265 nm. The method was validated with respect to linearity, precision
      (including intermediate precision), accuracy and specificity. The response was
      linear in the drug concentration range of 25-500 microg ml(-1). The mean values
      (+/-R.S.D.) of slope and correlation coefficient were 24256 (+/-0.679) and 0.9994
      (+/-0.0265), respectively. The R.S.D. values for intra- and inter-day precision
      studies were <0.210 and <1%, respectively. The recovery of the drug ranged
      between 99.7 and 101.5% from a mixture of degraded samples. The method even
      proved to be affective on application to a stressed marketed capsule formulation.

PMID- 15862696
TI  - Application of surface ionization methods for highly sensitive and selective
      analysis of benzodiazepine derivatives.
AB  - In this work, the results of studying the possibilities of surface ionization
      mass spectrometry (SI/MS) and atmosphere pressure thermodesorption surface
      ionization (APTDSI) spectroscopy for high-sensitivity and selective detection and
      identification of psychotropic preparations of benzodiazepine derivatives-
      medazepam, diazepam and chlordiazepoxide--are presented. It has been established
      that the SI mass spectra of benzodiazepines have a small number of lines and are
      significantly different from those obtained by electron ionization (EI) and that
      the molecules of benzodiazepines can be ionized by surface ionization with high
      efficiency (> or = 100 times and more than by EI) and the current density
      increases from diazepam to medazepam. It has been found that the APTDSI spectra
      of benzodiazepine derivatives have two characteristic maxima connected with
      energy of sublimation and desorption. The ionization efficiency is several C/g
      (Coulomb per gram), the linear range of the concentration dependence is 3-4
      orders of a magnitude. The results obtained by the SI/MS and APTDSI methods have
      been compared with those obtained by the conventional TLC and GC/MS with electron
      ionization.

PMID- 15862697
TI  - LC determination of leuprolide component amino acids in injectable solution by
      phanquinone pre-column derivatization labelling procedure.
AB  - A sensitive LC method for the determination of leuprolide acetate component amino
      acids in injectable solution with fluorogenic pre-column derivatization has been
      developed. The derivatization reaction with phanquinone was optimised by a series
      of experiments. Histidine, arginine, serine, tryptophan, glutamic acid, tyrosine,
      methionine, isoleucine, leucine and phenylalanine were separated on a reversed
      phase ODS column using as eluent a binary mixture of triethylammonium phosphate
      buffer-methanol, under gradient elution conditions. The derivatives were eluted
      in 30 min with good reproducibility. The hydrolysis reaction of the peptide was
      carried out at reflux with 12 N hydrochloric acid for 2 h 30 min. The intra-day
      accuracy of the entire procedure (hydrolysis, derivatization, LC separation)
      ranged from 80.5 to 109.5% of the nominal concentration of leuprolide acetate and
      the precision (%R.S.D.) was less than 5.8%; the inter-day accuracy was in the
      range 81.5-107.2% and corresponding R.S.D. values were less than 4.6%. The
      detection limits (signal-to-noise ratio=3) for the adducts are 30-800 fmol.

PMID- 15862698
TI  - Electrochemical, quantum-chemical and antioxidant properties of antipyrine and
      its derivatives.
AB  - Electrochemical, quantum-chemical and antioxidant properties of antipyrine and
      its derivatives have been investigated in this work. New quantum-chemical
      parameter such as difference of formation heats of a molecule and its cation
      radical (delta deltaH(cat)) has been used in order to describe properties of the
      investigated substances. Electrochemical properties (oxidation, reduction
      potentials) have been investigated. Correlation between the calculated delta
      deltaH(cat) and the experimentally obtained oxidation potentials for antipyrine
      and its derivatives has been found.

PMID- 15862699
TI  - Antioxidant and electrochemical properties of calcium and lithium ascorbates.
AB  - The calcium and lithium pharmaceutical products have been widely used in
      medicine, especially at diseases of the mind. Bioactivity and toxically of novel
      complex ascorbates of calcium and lithium were considered in this work. Study of
      antioxidant properties of new forms of the compounds was carried out by
      differential pulse voltammetry. Cyclic voltammetry was used for investigation of
      their electrochemical properties in order to obtain information about electron
      transfer reactions. The influence of these substances on the electrochemical
      oxygen reduction and its kinetic was also studied. As a result, the kinetic
      parameters interaction between reactive oxygen species and ascorbates of calcium
      and lithium were evaluated.

PMID- 15862700
TI  - PLE in the analysis of plant compounds. Part I. The application of PLE for HPLC
      analysis of caffeine in green tea leaves.
AB  - A broad spectrum of sample preparation methods is currently used for the
      isolation of pharmacologically active compounds from plant and herbal materials.
      The paper compares the effectiveness of infusion, microwave assisted solvent
      extraction (MASE), matrix solid-phase dispersion (MSPD) and pressurised liquid
      extraction (PLE) as sample preparation methods for the isolation of caffeine from
      green tea leaves. The effect of PLE variables, such as extraction temperature,
      pressure and time, on the yield of caffeine from the investigated matrix is
      discussed. The obtained results revealed that PLE, in comparison with other
      sample preparation methods applied, has significantly lower efficacy for caffeine
      isolation from green tea leaves. The evaluation of PLE conditions leads to the
      conclusion that elevated pressure applied in the PLE process is the factor
      hindering the extraction.

PMID- 15862701
TI  - PLE in the analysis of plant compounds. Part II: One-cycle PLE in determining
      total amount of analyte in plant material.
AB  - Pressurised liquid extraction (PLE) is recognised as one of the most effective
      sample preparation methods. Despite the enhanced extraction power of PLE, the
      full recovery of an analyte from plant material may require multiple extractions
      of the same sample. The presented investigations show the possibility of
      estimating the true concentration value of an analyte in plant material employing
      one-cycle PLE in which plant samples of different weight are used. The performed
      experiments show a linear dependence between the reciprocal value of the analyte
      amount (E*), extracted in single-step PLE from a plant matrix, and the ratio of
      plant material mass to extrahent volume (m(p)/V(s)). Hence, time-consuming multi
      step PLE can be replaced by a few single-step PLEs performed at different
      (m(p)/V(s)) ratios. The concentrations of rutin in Sambucus nigra L. and caffeine
      in tea and coffee estimated by means of the tested procedure are almost the same
      as their concentrations estimated by multiple PLE.

PMID- 15862702
TI  - Effects of intraoperative fluid infusions, sample storage time, and sample
      handling on unbound propofol assay in human blood plasma.
AB  - Free drug assay in physiological fluids is getting more and more attention
      nowadays. The principal reason is the fact that the unbound drug form is
      responsible for the therapeutic or toxic effects of its application. Unbound drug
      concentration significantly depends on the extent of its binding by plasma. This
      article describes the influence of different factors on unbound propofol
      concentration. These factors are presence of infusion fluids in blood, type of
      anticoagulant, sample storage time and plasma freezing. The following conclusions
      result from the experiments carried out: 1. The lowest free drug fractions are
      observed in samples containing carbohydrate infusion fluids. The free drug
      percentage is virtually independent of its total concentration in the range of
      clinically relevant concentrations. 2. There is no evident anticoagulant
      influence (heparin, citrate, EDTA and oxalate) on free propofol level in plasma
      samples. 3. Longer storage of plasma at 4 degrees C causes a slight rise of free
      propofol concentration in heparinised plasma and no evident changes in plasma
      containing citrate. 4. Plasma freezing induces the increase of free drug
      concentration both for citrate and heparin. These findings are valuable both for
      clinicists and pharmacologists, and important for chemical analysts.

PMID- 15862703
TI  - Determination of quality of pyridoxal-5'-phosphate enzyme preparations by
      spectroscopic methods.
AB  - The present study evaluates purified aspartate transaminase (AST, EC 2.6.1.1)
      preparations from three commercial sources. The enzyme molecule contains
      pyridoxal-5'-phosphate coenzyme (PLP), which provides AST characteristic
      absorption spectra in the wavelength range of 300-500 nm. The coenzyme bound in
      the active site also shows circular dichroism (CD) spectra in the same range.
      Besides, AST like other proteins may be modified in vitro or in vivo by reactions
      with other molecules, e.g. reactive sugars, and may form fluorescent products
      (advanced glycation end products, AGE). Spectroscopic methods were used to assess
      the quality of AST preparations from three different sources, Serva, Roche, and
      Sigma. Absorption spectra showed that the peak 360 nm characteristic of the
      active PLP form of AST prevailed in the Serva and Sigma preparations, while 330
      nm was the major peak in the Roche preparation. CD spectra demonstrated the major
      maximum at 360 nm in the Serva and Roche samples, thus suggesting the
      predominance of the active PLP form in both preparations. The Sigma sample showed
      a CD profile less characteristic of AST. Fluorescence measurements revealed
      formation of AGE in the case of the Roche preparation, while fluorescence of the
      other two preparations was low. In general, the Serva sample presented the most
      convenient properties of purified AST among the preparations tested. The results
      will be used for the selection of a commercial enzyme preparation applicable in
      our future spectroscopic studies of glycation of AST as a model protein and in
      our research of the influence of antioxidants on this process.

PMID- 15862704
TI  - Stability of ramipril in the solvents of different pH.
AB  - The stability of ramipril in the buffer solution with different pH and the
      influence of acid, alkaline and oxidative medium on ramipril stability were
      studied. The ramipril degradation products were determined by high-performance
      liquid chromatography (HPLC) method. Acetonitrile:sodium perchlorate was used as
      the mobile phase, at a flow rate of 1.0 ml/min (linear gradient elution). A
      Nucleosil 100-S 5 microm C18, 250 mm x 4.6 mm i.d. was utilized as stationary
      phase. Detection was affected spectrophotometrically at 210 nm. The drug
      substance was dissolved in the ammonium phosphate buffer (pH 3, 5 and 8) and
      these solutions were stored at 90 degrees C for 1 h. The other series of test
      solutions were prepared from stock solution (drug substance dissolved in solvent
      A of the mobile phase) by dilution in acid (0.1M HCl), alkaline (0.1M NaOH) and
      oxidative (hydrogen peroxide solution) medium. More then 0.2% of impurity D
      (ramipril-diketopiperazine) was detected in the buffer of pH 3 and pH 5. In the
      buffer of pH 8 there was detected more then 1% of impurity E (ramipril-diacid).
      No peaks for degradation products appeared in the chromatograms above limit of
      quantification. The alkaline medium has the greatest effect on degradation of
      ramipril into impurity E (more than 50%).

PMID- 15862705
TI  - Guidelines for the management of symptomatic breast disease.

PMID- 15862706
TI  - SOD, oxidative stress and human pathologies: a brief history and a future vision.
AB  - Superoxide dismutase (SOD) has now been known for 35 years. While the superoxide
      radical and SOD have been implicated in many disease states including
      inflammatory diseases, diseases of ischemia and reperfusion, neurodegenerative
      diseases, and cancer, as well as more subtle roles in cell signaling and perhaps
      in immune function, SOD is not yet in widespread usage in human clinical
      medicine. One obstacle has been that none of the three human SODs possesses
      attractive pharmacological properties to make it a clinically useful therapeutic
      agent. These problems may be overcome either by the design of SOD-mimetic drugs
      or by genetically re-engineering the human SOD genes to produce SODs with more
      desirable and controllable properties for human clinical usage. A second obstacle
      has been the fact that a delicate balance is involved between superoxide and SOD.
      Produced in proper amount, superoxide is a normal and useful metabolite, serving
      important roles as a signaling molecule in processes such as cell division, and
      even serving to act as a terminator of lipid peroxidation. When flagrantly
      overproduced, however, the radical can initiate lipid peroxidation, protein
      oxidation, and DNA damage, leading to cell dysfunction and death by apoptosis or
      necrosis. It is these paradoxical properties that complicate the precise
      restoration of optimal balance between superoxide and SOD when that balance has
      been upset by injury, disease, or aging.

PMID- 15862707
TI  - Mechanism of the tumor suppressive effect of MnSOD overexpression.
AB  - The mitochondrial antioxidant protein manganese-containing superoxide dismutase
      (MnSOD) has been shown to be a new type of tumor suppressor protein.
      Overexpression of MnSOD protein inhibits growth in a wide variety of cancer
      types. This review examines the molecular mechanism of the tumor suppressive
      effect of MnSOD. Three species have been proposed to cause the tumor suppressive
      effect: superoxide radical, hydrogen peroxide and nitric oxide. At the present
      time, the evidence appears strongest that hydrogen peroxide is the effector
      molecule since both catalase and glutathione peroxidase has been shown to
      modulate the effect. Surprisingly, in different cancer cell lines, overexpression
      of GPx has been found to both decrease and increase the growth inhibitory effect
      of MnSOD overexpression. Knowledge of which molecule causes the tumor suppressive
      effect of MnSOD and the mechanism of action will likely lead to new therapies for
      the treatment of cancer.

PMID- 15862708
TI  - Oxidative stress in organ preservation: a multifaceted approach to cardioplegia.
AB  - Every transplant is a reperfused organ and, therefore, undergoes some degree of
      oxidative damage. Postischemic reperfusion injury results in non-specific free
      radical-mediated acute endothelial damage, cell death and organ failure. The
      endothelium is a key site of injury from reactive oxygen species (ROS), and the
      endothelial cell dysfunction is central to the pathogenesis of arteriosclerosis.
      Accelerated arteriosclerosis, secondary to chronic allograft rejection, is a
      major long-term complication of heart transplantation. Therefore, preservation
      methods that would decrease injury during reperfusion are very important. We have
      developed a unique preservation solution, with a multifaceted approach, which
      best preserves the organ from ROS for an extended period of time before
      transplantation. The advantages of extending this period of preservation include
      an expansion of the donor pool, by permitting more distant procurement, the
      ability to perform detailed tissue typing, therefore, improves histocompatibility
      match and a reduction in emergency surgery as a result of graft rejection.

PMID- 15862709
TI  - Metal ion chelating peptides with superoxide dismutase activity.
AB  - The superoxide dismutase activities of two novel synthetic chelating peptides are
      reported. The peptides comprise a polyaminocarboxylic acid chelator (EDTA)
      conjugated to tyrosine (ET(1)) and phenylalanine (EP(1)). Superoxide dismutase
      (SOD) activity was exhibited for Cu(II) but not the Fe(III) complexes. The
      mimetic activities were compared to bovine erythrocyte SOD (3730 U/mg) and
      exhibited activities of 1119 U/mg for ET(1)-Cu(II) and 551 U/mg for EP(1)-Cu(II).
      Thus, small alterations in structure can have significant effects on the
      enzymatic activity of metallopeptides. These synthetic chelators have dual
      potential anti-inflammatory activity by chelating deleterious non-protein bound
      metal ions and concomitantly affording anti-oxidant mimetic activity.

PMID- 15862710
TI  - Characterization of superoxide production sites in isolated rat brain and
      skeletal muscle mitochondria.
AB  - In this report, we have quantified the superoxide and H(2)O(2) production rates
      of intact rat brain and skeletal muscle mitochondria under condition of oxygen
      saturation applying p-hydroxyphenylacetate as fluorescent probe for H(2)O(2)
      generation and hydroethidine as probe for superoxide formation. The localisation
      of superoxide producing sites was determined by evaluating the effects of SOD
      addition. At comparable respiration rates and functional quality of mitochondria,
      we detected in brain mitochondria, a high reversed electron flow-dependent
      H(2)O(2) generation while the bc(1)-complex-dependent H(2)O(2) generation in the
      presence of succinate+antimycin was low. On the other hand, the reversed electron
      flow-dependent superoxide generation rate was small while the bc(1)-complex
      dependent superoxide production was considerable. In contrast, isolated skeletal
      muscle mitochondria of comparable quality showed at almost comparable reversed
      electron flow-dependent H(2)O(2) generation more than 10-fold higher bc(1)
      complex-dependent H(2)O(2) generation. Our data are compatible with the following
      suppositions: (i) The major ROS generation site in complex I visible during
      reversed electron flow (very likely the FMN moiety) is liberating superoxide
      predominantly to the mitochondrial matrix space. (ii) Similarly, the bc(1)
      complex-dependent superoxide generation site (the semiquinone at center 'o')
      liberates superoxide with preference to the cytosolic space and (iii) Muscle
      mitochondria, most probably due to their higher endogenous CoQ content, generate
      at comparable maximal rates of respiration considerable larger amounts of
      superoxide at center 'o' of complex III.

PMID- 15862711
TI  - Differential modulation of normal and tumor cell proliferation by reactive oxygen
      species.

PMID- 15862712
TI  - Extracellular superoxide dismutase: structural and functional considerations of a
      protein shaped by two different disulfide bridge patterns.
AB  - The effects of reactive oxygen species are detrimental and can cause damage to
      DNA, protein, and lipids. Hence, the etiology of a large range of diseases
      resides in the generation of excess reactive oxygen species. However, these
      species are also involved in the maintenance of physiological functions. In
      tissues, it is therefore essential to maintain a steady-state level of
      antioxidant activity to allow both for the physiological functions of reactive
      oxygen species to proceed and at the same time preventing tissue damage.
      Extracellular superoxide dismutase (EC-SOD) is the only extracellular scavenger
      of the superoxide radical. The reactivity of superoxide is promiscuous and it is
      crucial that EC-SOD is positioned at the site of superoxide production to prevent
      adventitious reactions. It is therefore likely beneficial to have mechanisms for
      regulating the EC-SOD tissue distribution and enzymatic activity. The modular
      architecture of EC-SOD, encompassing three functional regions, is an ideal
      construction to generate diversity. By intracellular proteolytic processing and
      generation of active and inactive molecules, EC-SOD represents a flexible protein
      with the capacity to fine-tune the tissue localization and the antioxidant level
      in the extracellular space. The present review will address the function and
      activity of the separate regions of EC-SOD.

PMID- 15862713
TI  - Endothelial nitric oxide synthase protects the post-ischemic liver: potential
      interactions with superoxide.
AB  - Hepatic ischemia and reperfusion (I/R) continues to represent a significant cause
      of post-transplant liver failure. The roles that certain free radicals including
      nitric oxide (NO) and superoxide (O(2)(-)) play in this process are not well
      understood. The present study was designed to assess the role of endothelial cell
      nitric oxide synthase (eNOS) in I/R-induced liver injury in a murine model of
      hepatic I/R. Forty five minutes of partial (70%) hepatic ischemia followed by 3
      and 6 h of reperfusion resulted in a significant increase in liver injury which
      occurred in the absence of neutrophil infiltration. eNOS-deficient mice displayed
      enhanced liver injury when compared to their wild type controls again in the
      absence of neutrophil infiltration. Interestingly, basal liver blood flow was
      significantly decreased in these mice when compared to controls though their
      blood flow during reperfusion was not significantly reduced from their wild type
      controls. Treatment of eNOS(-/-) mice with gadolinium chloride, a potent
      inhibitor of Kupffer cell function, but not superoxide dismutase, significantly
      reduced post-ischemic hepatocellular injury while either treatment protected the
      wild type mouse livers. Taken together, these data suggest that NO derived from
      eNOS may act to protect the post-ischemic liver possibly by suppression of
      Kupffer cell function and not by modulation of tissue perfusion. Further the data
      presented here would indicate that the protective effects conferred by SOD are
      related to its ability to increase the bioavailability of NO rather than by
      attenuating superoxide-dependent reactions. Data generated from these studies may
      prove useful in developing new drug therapies to treat the post-ischemic liver.

PMID- 15862714
TI  - The metabolic hypothesis in amyotrophic lateral sclerosis: insights from mutant
      Cu/Zn-superoxide dismutase mice.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder
      characterized by selective loss of motor neurons and progressive muscle atrophy.
      A subset of patients harbors point mutations in the gene encoding Cu/Zn
      superoxide dismutase (SOD1), which allowed the generation of transgenic mice that
      express different SOD1 mutations and develop an ALS-like pathology. Recently, we
      reported in these mice the occurrence of a characteristic defect in energy
      homeostasis and the beneficial effect on the course of the disease of a high
      energy fat-enriched diet. In this review, we discuss the implication of these
      findings in the light of classical clinical observations concerning metabolic
      alterations in human ALS.

PMID- 15862715
TI  - Protective role of MnSOD and redox regulation of neuronal cell survival.
AB  - Reactive oxygen species (ROS) play a central role in neuronal pathophysiology and
      in neurodegenerative disorders. However, recent evidence indicates that these
      molecules also operate as signaling intermediates in a variety of physiological
      settings, including cell protection from apoptosis. Data presented here strongly
      support such a dual role for oxidants in neuronal cell homeostasis. In rat
      pheocromocytoma cells, cell rescue by the nerve growth factor (NGF) is
      accompanied by a transient burst of ROS generated in the cytosol by a GTPase
      dependent mechanism. Within the NGF signaling cascade, ROS lie upstream and are
      necessary for activation/phosphorylation of AKT/PKB and of the antiapoptotic
      transcription factor cAMP-responsive element-binding protein (CREB). Conversely,
      an increase in mitochondrial oxygen species heralds apoptosis of serum-deprived
      cells, and these events can be prevented by cell exposure to NGF or by treatment
      with the mitochondrially targeted antioxidant MitoQ. Importantly, NGF-mediated
      decrease of mitochondrial ROS is dependent on the transcriptional up-regulation
      of the manganese superoxide dismutase (MnSOD) by active CREB. These observations
      therefore outline a circuitry whereby cytosolic redox signaling promotes neuronal
      cell survival by increasing the mitochondrial antioxidant defenses.

PMID- 15862716
TI  - Anti-inflammatory properties of a chimeric recombinant superoxide dismutase:
      SOD2/3.
AB  - While superoxide dismutase (SOD) may be useful in treating inflammation, the
      problems of getting it into the blood in the right concentration, for long enough
      periods, and to the intended organ, have limited its translation into human
      clinical medicine. None of the three naturally occurring forms of human SOD is
      well suited for use as a therapeutic agent. SOD1 and SOD2 are normally
      intracellular enzymes and are rapidly cleared by the kidney. SOD3 occurs outside
      cells, but binds so tightly to cell surfaces or to collagen fibrils in the
      intracellular matrix that it remains largely in the few organs that secrete it.
      The "stickiness" of SOD3 results from a positively charged region in the
      hydrophilic C-terminus of each subunit. We have genetically engineered a hybrid
      chimeric SOD called SOD2/3 with greatly improved pharmacological properties. It
      has the sequence encoding the mature human SOD2 fused to the C-terminus of human
      SOD3. This hybrid SOD2/3 is highly expressed and easily purified. The molecule
      binds to endothelial cells, but less tightly than SOD3, and circulates well
      enough to become widely attached to extracellular surfaces, presumably in many
      tissues. The loose binding appears to produce a buffering effect on enzyme
      concentration, effectively eliminating bell-shaped dose-response curves. Single
      IV injections of SOD2/3 have protected experimental animals against a variety of
      models involving inflammation or ischemia/reperfusion.

PMID- 15862717
TI  - Modulation of skin tumorigenesis by SOD.
AB  - Generation of reactive oxygen species (ROS) has been implicated in the
      development of cancer. Groundwork establishing mitochondria as a critical source
      of ROS generation and the role of manganese superoxide dismutase (MnSOD) in
      preventing mitochondria-mediated cell death have been well established. In a
      seemingly contradictory role, it also is well documented that increased MnSOD
      expression suppresses the carcinogenesis effect of ROS. Our recent studies
      demonstrated that overexpression of MnSOD reduced tumor incidence in the two
      stage 7,12-dimethylbenz(a)-anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate
      (TPA) skin carcinogenesis model. However, reduction of MnSOD by heterozygous
      knockout of the MnSOD gene (Sod 2+/-) did not lead to an increase in tumor
      incidence. Thus, how modulation of mitochondrial ROS levels alter the outcome of
      developing cancer is unclear. This review will provide background information on
      the sequence of ROS-mediated events in the mitochondria and evidence that
      suggests that the antioxidant and tumor suppressor functions of MnSOD are indeed
      inter-related. It also will offer insights into the mechanisms by which MnSOD
      modulates the outcome of early stage skin carcinogenesis.

PMID- 15862718
TI  - A review of uses of health care utilization databases for epidemiologic research
      on therapeutics.
AB  - OBJECTIVE: Large health care utilization databases are frequently used in variety
      of settings to study the use and outcomes of therapeutics. Their size allows the
      study of infrequent events, their representativeness of routine clinical care
      makes it possible to study real-world effectiveness and utilization patterns, and
      their availability at relatively low cost without long delays makes them
      accessible to many researchers. However, concerns about database studies include
      data validity, lack of detailed clinical information, and a limited ability to
      control confounding. STUDY DESIGN AND SETTING: We consider the strengths,
      limitations, and appropriate applications of health care utilization databases in
      epidemiology and health services research, with particular reference to the study
      of medications. CONCLUSION: Progress has been made on many methodologic issues
      related to the use of health care utilization databases in recent years, but
      important areas persist and merit scrutiny.

PMID- 15862719
TI  - Activities of daily living (ADL) and instrumental activities of daily living
      (IADL) items were stable over time in a longitudinal study on aging.
AB  - OBJECTIVE: The purpose of this analysis was to examine the stability over time of
      the activities of daily living (ADL) and instrumental activities of daily living
      (IADL) items in the Aging in Manitoba (AIM) Longitudinal Study and to evaluate
      the existence of differential item functioning across settings (home, nursing
      home). STUDY DESIGN AND SETTING: The study used data from 607 participants of the
      AIM Longitudinal Study who were more than 85 years of age in 1996 and who had
      complete data from 1983, 1990, and 1996 for all ADL and IADL items. Rasch
      analysis was used to examine how the rating scale of the ADL and IADL items was
      used by participants, and to determine if the ordering of items remained stable
      across three time periods (1983, 1990, 1996) and the two different settings
      (home, nursing home). RESULTS: The rating scale worked best when dichotomized
      into "received no assistance" and "receives assistance." Except for four items
      (making tea, making meals, doing nursing care, and going outside in any weather),
      the items were stable across administration periods, and across settings.
      CONCLUSION: The AIM can be used to evaluate changes in disability over time and
      may have the potential to identify those at risk for transitions in care.

PMID- 15862720
TI  - The validity and ethics of giving placebo in a randomized nonpharmacologic trial
      was evaluated.
AB  - OBJECTIVE: When studying the effects of a non-pharmacologic intervention, the
      choice of a control group is often difficult. In a study on the effectiveness of
      increased water intake on voiding dysfunction in elderly men we used an unusual
      design. This article addresses the internal validty and ethics of this design.
      STUDY DESIGN AND SETTING: The randomized trial we evaluated had a 6-month follow
      up period and was carried out among 141 elderly men with moderate lower urinary
      tract symptoms. The experimental group was given the instruction to drink more
      water, the control group received placebo medication. The participants were not
      informed that there was a 50% chance of receiving placebo. We measured whether
      the prior expectations and preferences were comparable for the two study groups,
      whether blinding was preserved throughout the study period, and whether the
      participants considered this design ethical. RESULTS: Prior to randomization,
      patients had higher expectations for the experimental intervention, but there was
      not statistically significant difference in their preference. During the study
      period, two out of 71 patients in the control group unmasked the placebo. In
      general, both groups fully agreed with the informed consent procedure.
      CONCLUSION: This design can be considered when the effects of a non-pharmacologic
      interventions are studied.

PMID- 15862721
TI  - Using randomized controlled trial data, the agreement between retrospectively and
      prospectively collected data comprising the pneumonia severity index was
      substantial.
AB  - OBJECTIVE: To assess the agreement between prospectively and retrospectively
      determined variables comprising the Pneumonia Severity Index (PSI), assignment to
      PSI risk class, and designation as low risk, based on these two methods of data
      collection. STUDY DESIGN AND SETTING: We analyzed data from a randomized trial of
      patients with community-acquired pneumonia managed in 32 hospital emergency
      departments (EDs). For all enrolled patients, the 20 PSI variables were collected
      prospectively by ED providers and retrospectively by medical record abstractors.
      We examined the agreement for each of the 20 PSI variables, assignment to the
      five PSI risk classes, and classification of patients as low (classes I-III) vs.
      high (classes IV and V) risk. Agreement was measured using total percent
      agreement and the kappa statistic. RESULTS: Among the 3,220 enrolled patients,
      percent agreement was >90% for 18 of the 20 variables comprising the PSI, with
      most unweighted kappa's being >0.6. Agreement was substantial for assignment to
      PSI risk class (percent agreement: 92.7%; weighted kappa: 0.79) and for
      classification as low vs. high risk (percent agreement: 88.5%; unweighted kappa:
      0.74). CONCLUSION: There was substantial agreement between retrospective and
      prospective assignment to PSI risk class, classification as low vs. high risk,
      and the determination of most individual variables that constitute the PSI.

PMID- 15862722
TI  - Breast cancer survivors accurately reported key treatment and prognostic
      characteristics.
AB  - BACKGROUND AND OBJECTIVE: Medical records are considered the gold standard for
      information on cancer treatments and prognosis. We compared survivor self-report
      and medical records for agreement on key treatment and prognostic
      characteristics. STUDY DESIGN AND SETTING: A population-based study was conducted
      in Quebec assessing work experience among breast cancer survivors aged <60 years
      at diagnosis. Data came from a single telephone interview 3.4 +/- 0.2 years after
      diagnosis. Medical record data were available for 103 out of 646 participants.
      RESULTS: Agreement of self-report with medical record data was very high for
      treatments (breast surgery, type of mastectomy, axillary dissection,
      radiotherapy, chemotherapy, hormone therapy, reconstruction, bone marrow
      transplantation). Kappa values varied from 0.89 for axillary dissection to 1.00
      for breast surgery. Kappa values for number of invaded nodes (0, 1-3, >/=4,
      unknown) was slightly lower (0.85) but was still excellent. When accepting
      answers +/-1 month of the medical record date, >/=89% of women correctly reported
      different treatment dates. CONCLUSION: These results provide evidence of the
      validity of summary treatment and prognostic data reported by breast cancer
      survivors 3 years after diagnosis. Survivors can likely accurately describe the
      treatment trajectory and key prognostic information when medical record review is
      unfeasible. These findings may need replication among older women.

PMID- 15862723
TI  - Depression screening instruments made good severity measures in a cross-sectional
      analysis.
AB  - OBJECTIVE: Test equivalence of different survey instruments to diagnose
      depression and to assess its severity. Where equivalence exists, describe how to
      convert scores between instruments. STUDY DESIGN: Cross-sectional analysis of six
      convenience samples consisting of 71 members of a health plan and 107 patients of
      mental health specialty practices with psychiatric diagnoses were compared using
      the Beck Depression Inventory (BDI) and one or more of the Primary Care Screener
      for Affective Disorder, Prime-MD-PHQ, Inventory to Diagnose Depression, the
      depression subscale of the Psychiatric Diagnostic Screening Questionnaire, and
      the Mental Health Inventory from the SF-36. RESULTS: Correlations between the
      screening instruments and the BDI ranged from 0.79 to 0.95 and the sensitivity to
      depression and the specificity against nondepressive mental health diagnoses was
      equally good or better. We also describe a method for equating severity scores
      across instruments and labeling the screener-based severity measures with
      clinically meaningful descriptions comparable to those used for the BDI.
      CONCLUSIONS: Screener-based severity measures extensively overlap each other.
      Good screeners for depression can also be good severity instruments. Exploiting
      screeners as severity instruments can significantly reduce response burden
      without sacrificing performance.

PMID- 15862724
TI  - Equally valid models gave divergent predictions for mortality in acute myocardial
      infarction patients in a comparison of logistic [corrected] regression models.
AB  - OBJECTIVE: Models that predict mortality after acute myocardial infarction (AMI)
      contain different predictors and are based on different populations. We studied
      the agreement and validity of predictions for individual patients. STUDY DESIGN
      AND SETTING: We compared predictions from five predictive logistic regression
      models for short-term mortality after AMI. Three models were developed
      previously, and two models were developed in the GUSTO-I data, where all five
      models were applied (n =40,830, 7.0% 30-day mortality). Agreement was studied
      with weighted kappa statistics of categorized predictions. Validity was assessed
      by comparing observed frequencies with predictions (indicating calibration) and
      by the area under the receiver operating characteristic curve (AUC), indicating
      discriminative ability. RESULTS: The predictions from the five models varied
      considerably for individual patients, with low agreement between most (kappa
      <0.6). Risk predictions from the three previously developed models were on
      average too high, which could be corrected by re-calibration of the model
      intercept. The AUC ranged from 0.76-0.78 and increased to 0.78-0.79 with re
      estimated regression coefficients that were optimal for the GUSTO-I patients. The
      two more detailed GUSTO-I based models performed better (AUC approximately 0.82).
      CONCLUSION: Models with different predictors may have a similar validity while
      the agreement between predictions for individual patients is poor. The main
      concerns in the applicability of predictive models for AMI should relate to the
      selected predictors and average calibration.

PMID- 15862725
TI  - Conventional models overestimate the statistical significance of volume-outcome
      associations, compared with multilevel models.
AB  - OBJECTIVE: To compare the use of conventional statistical models with multilevel
      regression models in volume-outcome analyses of surgical procedures in an
      empirical case study. STUDY DESIGN AND SETTING: Using conventional regression
      models and multilevel regression models, we estimated the effect of hospital
      volume and surgeon volume on 30-day mortality and length of postoperative
      hospital stay in persons who had an esophagectomy, pancreaticoduodenectomy, or
      major lung resection for cancer in Ontario, Canada, from 1994 to 1999. RESULTS:
      The point estimates of volume-outcome associations were similar using either
      method; however, the 95% confidence intervals estimated by multilevel models were
      wider than those estimated by conventional models. A significant association
      between volume and mortality was identified in 2 of 18 (11%) comparisons using
      conventional analysis but in none of the 18 (0%) comparisons using multilevel
      analysis, and between volume and length of stay in 15 of 18 (83%) comparisons
      using conventional analysis and in 1 of 18 (6%) comparisons using multilevel
      analysis. CONCLUSION: Conventional and multilevel statistical models can yield
      substantially different results in the analysis of volume-outcome associations
      for surgical procedures.

PMID- 15862726
TI  - In a diagnostic test study the validity of three serodiagnostic test was compared
      in patients with liver echinococcosis.
AB  - BACKGROUND AND OBJECTIVE: To determine the efficacy of immunoprecipitation (DD5),
      enzyme immunoanalysis (ELISA-IgG), and immunoelectrotransference or Western blot
      (WB) in patients with liver echinococcosis (LE) used separately, in parallel and
      in series. METHODS: Diagnostic test study. DD5, ELISA-IgG, and WB were applied in
      75 patients with LE and 75 with cholelithiasis. Surgery was considered a
      reference standard. The sample size was calculated assuming a 99% confidence
      interval (99% CI), expected sensitivity (S) of 90% and a worst result of 80%;
      expected specificity (SP) of 95% and a worst result of 85%. S, SP, and predictive
      values (PPV and NPV) were calculated. RESULTS: The best S was verified with ELISA
      IgG and WB (82.7%) and the best SP with DD5 (94.7%). DD5 presented a better PPV
      (92.9%) and WB a better NPV (83.5%). When applying the tests in parallel, the
      best S was obtained from the combination of DD5 and WB (82.7%); and the best SP,
      PPV and NPV with ELISA-IgG and WB (88.0%, 87.3%, and 83.5%, respectively).
      CONCLUSIONS: DD5 appears as the most specific test and as having greater PPV;
      ELISA-IgG and WB are more sensitive. The combined use of these tests does not
      improve diagnosis validity.

PMID- 15862727
TI  - High incidence and recurrence of shoulder and neck pain in nursing home employees
      was demonstrated during a 2-year follow-up.
AB  - OBJECTIVE: This study describes the course of shoulder and neck complaints in a
      working population over time. STUDY DESIGN AND SETTING: Questionnaires were
      administered on neck and shoulder complaints over 3 consecutive years. RESULTS:
      We observed 12-month incidence rates for neck and shoulder complaints of 16% to
      18%, 12-month prevalence rates roughly twice as high, and 12-month recurrence
      rates approximately twice the prevalence rates. Each year, medical care was
      sought by 21% to 38% of the subjects with neck or shoulder pain, and 13% to 21%
      were absent from work. Although at the population level the occurrence of neck
      and shoulder complaints remained constant, the course of complaints within
      individuals demonstrated a strong episodic nature of neck and shoulder pain.
      Results from this study suggest that neck and shoulder complaints for most
      subjects run a recurrent course characterized by a strong variation in occurrence
      and a self-limiting course. CONCLUSION: These findings suggest that clinical
      trials should have a sufficiently long follow-up period to demonstrate
      sustainability of the therapeutic results.

PMID- 15862728
TI  - A nationwide survey of physician office visits found that inappropriate
      antibiotic prescriptions were issued for bacterial respiratory tract infections
      in ambulatory patients.
AB  - OBJECTIVE: Correlations between probabilities of resistance and the frequencies
      with which antibiotics were prescribed for treating bacterial respiratory
      infections were examined in a nationwide ambulatory population. STUDY DESIGN AND
      SETTING: The data of a nationwide probability sample survey of visits to
      physician offices in the United States in 1999 were used to conduct this study of
      drug use. A clinical pharmacologist identified antibiotics prescribed during
      those visits using a large online database. The participating physicians
      diagnosed the bacterial respiratory infections. An infectious disease expert
      determined the probabilities of bacterial resistance from a nationwide antibiotic
      surveillance database. RESULTS: Various bacterial respiratory infections were
      diagnosed during 6.5% of physician office visits in 1999. One or more antibiotics
      were prescribed during 51.0% of those visits. The probabilities of resistance to
      the most frequently prescribed antibiotics varied from 20% to 40% and showed a
      weak positive correlation with the frequencies of antibiotic prescriptions.
      CONCLUSION: A significant number of inappropriate antibiotic prescriptions were
      issued for infections with a high probability of bacterial resistance to the
      prescribed antibiotics.

PMID- 15862729
TI  - Electronic mail was not better than postal mail for surveying residents and
      faculty.
AB  - OBJECTIVE: To compare response rate, time to response, and data quality of
      electronic and postal surveys in the setting of postgraduate medical education.
      STUDY DESIGN AND SETTING: A randomized controlled trial in a university-based
      internal medicine residency program. We randomized 119 residents and 83 faculty
      to an electronic versus a postal survey with up to two reminders and measured
      response rate, time to response, and data quality. RESULTS: For residents, the e
      survey resulted in a lower response rate than the postal survey (63.3% versus
      79.7%; difference -16.3%, 95% confidence interval (95% CI) -32.3% to -0.4%%;
      P=.049), but a shorter mean response time, by 3.8 days (95% CI 0.2-7.4; P=.042).
      For faculty, the e-survey did not result in a significantly lower response rate
      than the postal survey (85.4% vs. 81.0%; difference 4.4%, 95% CI -11.7 to 20.5%;
      P=.591), but resulted in a shorter average response time, by 8.4 days (95% CI 4.4
      to 12.4; P < 0.001). There were no differences in the quality of data or
      responses to the survey between the two methods. CONCLUSION: E-surveys were not
      superior to postal surveys in terms of response rate, but resulted in shorter
      time to response and equivalent data quality.

PMID- 15862730
TI  - Test-retest of self-reported exposure to artificial tanning devices, self-tanning
      creams, and sun sensitivity showed consistency.
AB  - OBJECTIVE: Exposure to ultraviolet radiation has consistently been linked to an
      increased risk of melanoma. Epidemiologic studies are susceptible to measurement
      error, which can distort the magnitude of observed effects. Although the
      reliability of self-report of many sun exposure factors has been previously
      described in several studies, self-report of use of artificial tanning devices
      and self-tanning creams has been less well characterized. STUDY DESIGN AND
      METHODS: A mailed survey was re-administered 2-4 weeks after completion of the
      initial survey to 76 randomly selected participants in a case-control study of
      melanoma. Cases and controls were individuals diagnosed in 1999 and 2000 who were
      ascertained from the Iowa Cancer Registry in 2002. We assessed the consistency of
      self-reported use of sunlamps and self-tanning creams, sun sensitivity, and
      history of sunburns. RESULTS: There was substantial reliability in reporting the
      use of sunlamps or self-tanning creams (cases: Kappa (kappa)=1.0 for both
      exposures; controls: kappa=0.71 and 0.87, respectively). kappa estimates of 0.62
      0.78 were found for overall reliability of several sun sensitivity factors.
      CONCLUSION: Overall, the survey instrument demonstrated substantial
      reproducibility for factors related to the use of sunlamps or tanning beds, self
      tanning creams, and sun sensitivity factors.

PMID- 15862732
TI  - The synergy model: the ultimate mentoring model.
AB  - Clarian Health Partners is a system that includes Methodist Hospital of Indiana,
      Indiana University Hospital, and Riley Hospital for Children. The nurses of
      Clarian Health Partners are the recipients of many national awards for their
      leadership and innovations in critical care. Nurse leaders at Clarian have
      developed and implemented a unique framework for professional development based
      on the synergy model. In this article, the Chief Nurse Executive for the System,
      Dr. Karlene Kerfoot, and Marilyn Cox, the Senior Vice President for Nursing and
      Patient Care at Riley Hospital for Children, describe their vision of and
      strategies for a new approach to mentoring professional nursing staff.

PMID- 15862733
TI  - Synergy: a framework for leadership development and transformation.
AB  - The Synergy Model has been adopted as an organizing framework for nursing
      practice, education, and leadership at Clarian Health Partners, Inc. of Indiana.
      This article describes the evolution of educational programs at Clarian, in
      concert with the implementation of the Synergy Model. Philosophical and
      operational changes in staff orientation, professional development, and
      management development are described.

PMID- 15862734
TI  - Mentoring staff members as patient safety leaders: the Clarian Safe Passage
      Program.
AB  - This article describes a second element of the Synergy Model of Patient Care
      implemented by Clarian Health Partners of Indiana. The Clarian Safe Passage
      Program is a unique approach to the promotion of patient safety. In this program,
      frontline staff nurses are trained to serve as Safe Passage nurses, who are unit
      based safety experts. These nurses mentor each other and their peers in acquiring
      patient safety expertise and promoting a free flow of information to avert actual
      and potential errors in health care delivery.

PMID- 15862735
TI  - Excellence in evidence-based practice: organizational and unit exemplars.
AB  - The University of Iowa Hospitals and Clinics is a recognized leader in evidence
      based practice. Creating organizational excellence in evidence-based practice
      takes leadership and a committed effort at all levels. Building the capacity,
      culture, and vision at the organizational and unit levels is needed to promote
      use of evidence in practice. Practical approaches that have been effective in
      promoting development of an evidence-based practice program and project are
      outlined. An exemplar describing development and adoption of an evidence-based
      project to improve sedation management led to improvements in patient care
      processes and outcomes.

PMID- 15862736
TI  - Interdisciplinary collaboration: the heart and soul of health care.
AB  - In a health care system in which patient complexity, outcome indicators, and
      informed families are representative of current reality, an interdisciplinary
      approach to care is crucial to successful navigation of a patient's experience in
      the ICU. To guide practitioners toward favorable patient progression, a thorough
      understanding of interdisciplinary collaboration is necessary. This article
      focuses on definitions of, benefits of, and barriers to interdisciplinary
      collaboration and provides practical solutions for implementation.

PMID- 15862738
TI  - Journey to the Beacon Award: the Georgetown University Hospital perspective.
AB  - The medical intensive care unit (MICU) at Georgetown University Hospital in
      Washington, D.C., was among the first four hospitals to be awarded the Beacon
      Award from the American Association of Critical- Care Nurses. The Beacon Award is
      given to those units that prove, through a 42-question application, how they
      excel and serve as a guiding light to other intensive care units. The MICU's
      "journey" to the award prompted an introspective look into the unit, its
      policies, and its methods of providing the highest quality patient care, in an
      environment that is supportive to the nursing staff.

PMID- 15862739
TI  - The road to excellence: Magnet designation, the Beacon Award, and primary
      nursing.
AB  - The potential to have a unit based on excellence is within every manager's reach.
      The ability to submit for the Beacon Award and Magnet hospital designation are
      two avenues to fulfill that potential. Successes from University of California
      Davis Medical Center are shared in this article in the hope of inspiring other
      managers and their staff.

PMID- 15862740
TI  - A step ahead: strategies for excellence in critical care nursing practice.
AB  - The adult intensive care unit (ICU) at Baystate Medical Center is a 24-bed
      medical-surgical-trauma ICU that provides high-quality care to critically ill
      patients. Collaboration and expertise among the nursing staff, intensivists, and
      interdisciplinary colleagues have contributed to its development into a Beacon
      Award-winning unit. Its primary goal is reflected in the unit's mission: "Care
      for our patients is guided by knowledge, motivated by compassion, and performed
      in collaboration with others." Common interests, values, and purposes have
      created an environment of communication that supports the delivery of exceptional
      critical care to patients and their families.

PMID- 15862737
TI  - The Methodist Hospital CCU: a Beacon unit of excellence.
AB  - This article features the Coronary Care Unit of The Methodist Hospital of
      Houston, Texas. This unit was one of the first Beacon Critical Care Units
      recognized by the American Association of Critical Care Nurses. This article
      focuses on how to achieve this award. The Coronary Care Unit nursing
      infrastructure is described, and specific unit examples are included.

PMID- 15862741
TI  - Strategies for success in the acute care nurse practitioner role.
AB  - This article reviews issues related to development of the role of the acute care
      nurse practitioner (ACNP). Strategies for ensuring success in the role are
      outlined, including the importance of communication about the role, maintaining
      competency, forming collaborative relationships, and the value of networking. The
      ACNP represents an innovative role in advanced practice nursing. Demonstrating
      the outcomes of ACNP practice ensures recognition of the impact and value of this
      unique role.

PMID- 15862742
TI  - Transport of the critically ill: the Northwest MedStar experience.
AB  - This article provides a description of Northwest MedStar, a fully integrated,
      self-sustained critical care transport program that provides transport services
      to over 70 hospitals and 350 emergency medical service agencies in the inland
      Northwest region of the United States. By providing transport and educational
      support to these agencies, Northwest MedStar assists in providing optimal
      emergency and critical care services for the patients in their communities.

PMID- 15862743
TI  - From revelation to revolution: critical care nurses' emerging roles in public
      policy.
AB  - Nursing history is rich with individuals who have overcome barriers to impact
      their environment. Florence Nightingale not only introduced nursing as a science;
      she was also one of the first public policy advocates. She looked at an unhealthy
      environment, and used her political skills to effect change. Nursing
      organizations are mirroring this patient advocacy role in many forums. This
      article discusses the varying attitudes toward the role of nurses in public
      policy, from indifference to action. Suggestions for changes in the educational
      process are reviewed. Finally, public policy strategies for critical care nurses
      to use in tobacco control and end-of-life care are discussed.

PMID- 15862744
TI  - Are we close to the clinical development of novel drugs targeting telomeres and
      telomerase?

PMID- 15862745
TI  - Overcoming the immortality of tumour cells by telomere and telomerase based
      cancer therapeutics--current status and future prospects.
AB  - A key property of malignant tumours is their immortality or limitless replicative
      potential. Cell replication is associated with the maintenance of telomeres and
      in the great majority of cases, through the reactivation of the reverse
      transcriptase telomerase. Targeting the telomere/telomerase machinery offers a
      novel and potentially broad-spectrum anticancer therapeutic strategy since
      telomerase is constitutively overexpressed in the vast majority of human cancers.
      Telomeres are also critically short in most tumours compared to normal tissues.
      Strategies that exploit these differences include the direct targeting of
      components of telomerase: the protein component hTERT or RNA component hTR.
      Examples of such agents include the small molecule hTERT inhibitor BIBR1532 and
      GRN163L, a thio-phosphoramidate oligonucleotide targeting the template region of
      hTR as a "template antagonist". Anti-tumour effects have been observed in both
      cell lines and, especially for GRN163L, in xenografted human tumours in mice.
      Effects, however, are largely dependent upon initial telomere length, which can
      result in a substantial lag before antitumour activity is observed in tumours
      possessing relatively long telomeres. An alternative approach is to target the
      telomere itself (Telomere Targeting Agents, TTAs). Several classes of small
      molecules have been described that induce the G-rich single-stranded overhang of
      telomeric DNA to fold into 4-stranded G-quadruplex structures. Such folding is
      incompatible with telomerase function and may induce rapid telomere uncapping.
      These molecules have shown potent telomerase inhibition in nanomolar
      concentrations in vitro and the rapid induction of senescence in cancer cells.
      The trisubstituted acridine based TTA, BRACO19, has demonstrated single agent
      activity against human tumour xenografts with anti-tumour effects apparent from
      only 7 days of treatment. In the near future, it is expected that lead examples
      from both the direct telomerase targeted agents (e.g., GRN163L) and from the
      distinct class of those targeting telomeres (e.g., AS1410 based on BRACO19) will
      enter Phase I clinical trial where clinical benefit from this class of novel
      drugs will be determined.

PMID- 15862746
TI  - Glutathione s-transferase polymorphisms (GSTM1, GSTP1 and GSTT1) and the risk of
      acute leukaemia: a systematic review and meta-analysis.
AB  - Glutathione s-transferase (GST) polymorphisms (GSTM1, GSTP1 and GSTT1) have been
      considered as risk factors for developing acute leukaemia in a number of studies;
      however the overall results of such studies are inconsistent. To investigate a
      putative association of GST polymorphisms with the risk of acute leukaemia, we
      performed a systematic review and meta-analysis of 30 published case-control
      studies. To take into account the possibility of heterogeneity across the
      studies, a statistical test was performed. The pooled odds ratios (ORs) were
      assessed using both a fixed-effects and a random-effects model. The pooled OR of
      acute leukaemia risks associated with GSTM1 null genotype, GSTP1 Val105 allele
      and GSTT1 null genotype were 1.22 (95% confidence interval (CI) 1.07-1.38), 1.07
      (95% CI 1.00-1.13) and 1.19 (95% CI 1.00-1.41), respectively. Significantly
      increased risk of acute lymphoblastic leukaemia associated with GSTM1 and GSTT1
      null genotypes was observed. Their pooled ORs were 1.24 (95% CI 1.17-1.31) and
      1.30 (95% CI 1.06-1.60), respectively. We also found substantial evidence of
      heterogeneity between the studies. Our results suggest that GSTM1 and GSTT1, but
      not GSTP1 polymorphisms, appear to be associated with a modest increase in the
      risk of acute lymphoblastic leukaemia. It is conceivable that GSTM1 and GSTT1
      null genotypes may thus play a role in leukemogenesis. A review of the 30 case
      control studies indicates that greater attention should be paid to the design of
      future studies.

PMID- 15862747
TI  - Intention to test for prostate cancer.
AB  - The aim of this study was to assess intention among men to take a prostate
      specific antigen (PSA) test, when this test was: (i) offered by a doctor or (ii)
      based on the men's own initiative. A further aim was to use the Theory of Planned
      Behaviour (TPB) to predict the most important determinants for taking a PSA test.
      In addition, the intention to take a PSA test among men who had the opportunity
      to read a PSA leaflet published by the Swedish Cancer Society was compared with
      men who had not read the leaflet. A total of 1000 men, age range 40-70 years,
      were selected randomly from a population database. The TPB model was used to
      measure attitudes about PSA testing. The constructed questionnaire was posted to
      the selected sample. Half of the sample received only the TPB questionnaire and
      the other half also received a PSA leaflet. The response rate was approximately
      63%. The results showed that men would be less likely to request a PSA test if
      their doctor did not suggest the test (mean approximately 3.8 (range 1-7 from not
      likely to very likely)). However, if they were offered the test, most would take
      it (mean approximately 6.0 (range 1-7)). The positive "Attitude factor" towards
      the test was the most salient predictor of both behaviours. In addition, the
      probability of requesting a test was higher among those who had already taken a
      PSA test. The men who did not receive the PSA leaflet reported a higher intention
      to take the test than those who had received it. Overall, 47% of the variance was
      explained concerning men's intention to take a PSA test when offered by a doctor
      and 25% of men's intention to request the PSA test themselves. In conclusion, the
      majority of men in this study had a positive attitude towards PSA testing. The
      results indicate that most men could be expected to accept screening. The
      intention to take the PSA test was lower among the men who had received the PSA
      leaflet.

PMID- 15862748
TI  - Survival in Hodgkin's disease patients--report of 25 years of experience at the
      Milan Cancer Institute.
AB  - The aim of this study was to assess the long-term therapeutic outcome and risk of
      treatment-related complications in Hodgkin's disease. From May 1973 to September
      1990, four randomised studies have been activated at the Milan Cancer Institute
      using nitrogen mustard, vincristine, procarbazine and prednisone (MOPP) and
      doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) regimens, with or
      without irradiation, involving a total of 811 patients with intermediate and
      advanced Hodgkin's disease. Overall, ABVD contributed to significantly reduce the
      relative risk of lymphoma progression and death compared with the MOPP regimen.
      With a prolonged follow-up, a total of 106 patients (75 of whom were in
      continuous complete remission after first-line chemotherapy) developed a variety
      of cancers, resulting in a total risk of 22.2%. Our 25 years of experience re
      emphasises that ABVD can cure a high fraction of patients with Hodgkin's disease.
      However, patients in continuous complete remission, are at a high risk of
      developing second cancers, especially when the treatment strategy includes
      extensive irradiation. The main focus of future trials should be on reducing
      treatment sequelae to improve the quality of life of long-term survivors.

PMID- 15862749
TI  - Assessment of pre-treatment cognitive performance in adult bone marrow or
      haematopoietic stem cell transplantation patients: a comparative study.
AB  - The aim of this study was to examine cognitive performance in patients prior to
      bone marrow or haematopoietic stem cell transplantation (SCT) and in
      haematological patients who received non-myeloablative cancer therapies. A
      consecutive sample of 101 SCT patients and 82 haematological patients completed a
      neuropsychological test battery and five questionnaires assessing subjective
      cognitive complaints, psychological functioning, health-related quality of life
      and fatigue. Results were compared with normative data. Percentages of
      cognitively impaired patients were equally divided between groups. Most deficits
      were observed in visual memory, visuospatial and constructional ability and
      psychomotor functions. The SCT group showed a higher rate of anxiety cases and
      reported lower cognitive, emotional and social functioning. Results of
      neuropsychological testing were not associated with outcome of the
      questionnaires. This study showed impaired cognitive performance prior to SCT.
      Haematological patients treated with non-myeloablative cancer therapies proved to
      be a reliable reference group for longitudinal studies.

PMID- 15862750
TI  - Activated Akt expression in breast cancer: correlation with p53, Hdm2 and patient
      outcome.
AB  - Activation of protein kinase-B/Akt (pAkt) is mediated by oestrogen and involves
      HER-2 in vitro, to phosphorylate Hdm2 and influence p53 cytoplasmic localisation
      and degradation. Expression of all active Akt isoforms (pAkt) were examined,
      together with p53/Hdm2 subcellular expression in invasive ductal breast cancers
      (IDCs), to evaluate whether in vitro findings were related to clinical data and
      determine the effect on outcome. Immunohistochemical expression of serine 473
      specific phosphorylated Akt (pAkt) isoforms (Akt-1,2,3) was evaluated in 97
      patients, together with subcellular expression of p53/Hdm2. The results show that
      pAkt was evaluable in 95 patients with cytoplasmic expression in 81% and more
      likely to be associated with larger tumours (P=0.007), with no correlation with
      HER-2 expression. pAkt correlated with increasing levels of cytoplasmic p53
      (P=0.025) and was associated with a reduced disease-free survival (P=0.04;
      univariate). In conclusion, pAkt has implications in breast cancer growth through
      mechanisms inactivating p53 with an association with immunohistochemical p53
      expression, which is preferentially cytoplasmic. Despite in vitro associations,
      pAkt appears to be a variable marker of HER-2 expression.

PMID- 15862751
TI  - Increased carotid wall thickening after radiotherapy on the neck.
AB  - Patients treated for head and neck tumours with local radiotherapy (RT) on the
      neck harbour an increased risk of stroke. This may be due to accelerated
      atherosclerotic changes within the RT-field; however, the real impact of local RT
      on the carotid artery remains debatable. The aim of the present study was to
      assess the difference in carotid wall thickness (intima-media thickness) in 42
      unilaterally irradiated parotid tumour patients by performing B-mode
      ultrasonography. A mean difference in intima-media thickness (IMT) of the
      irradiated compared with the non-irradiated carotid artery of 0.30 mm (P=0.031)
      was found. A significant correlation was established with a longer post-RT
      interval (P=0.008). RT on the neck is associated with increased thickening of
      carotid IMT. Screening and treatment of additional cerebrovascular risk factors
      which contribute to further IMT thickening and stroke development is recommended,
      especially in radiotherapy patients with a favourable prognosis.

PMID- 15862752
TI  - Guidelines for surgical treatment of hepatoblastoma in the modern era-
      recommendations from the Childhood Liver Tumour Strategy Group of the
      International Society of Paediatric Oncology (SIOPEL).
AB  - Cisplatin-containing chemotherapy and complete surgical resection are both
      crucial in the cure of hepatoblastoma. Radical resection can be obtained either
      conventionally by partial hepatectomy or with orthotopic liver transplant, but
      the surgical approach to hepatoblastoma differs considerably across the world.
      Our main aim in this paper is to present the surgical recommendations of the
      Childhood Liver Tumour Strategy Group of the International Society of Paediatric
      Oncology (SIOPEL), as well as to stimulate international debate on this issue. We
      discuss biopsy, verification of resectability, resection principles, indications
      and potential contraindications for orthotopic liver transplant, as well as
      thoracic surgery for pulmonary metastases. We suggest that heroic liver
      resections with a high probability of leaving residual tumour should be avoided
      whenever possible. In such cases primary orthotopic liver transplant should be
      considered. Superior survival rates in hepatoblastoma patients who have received
      a primary transplant after a good response to chemotherapy support the strategy
      of avoiding partial hepatectomy in cases where radical resection appears
      difficult and doubtful. We recommend early referral to a transplant surgeon in
      cases of: (i) multifocal or large solitary PRETEXT IV (PRE Treatment EXTent of
      disease scoring system) hepatoblastoma involving all four sectors of the liver
      and (ii) unifocal, centrally located tumours involving main hilar structures or
      main hepatic veins. Because complete tumour resection is a prerequisite for cure,
      any strategy leading to an increased resection rate will result in improved
      survival. We advise the more frequent use of orthotopic liver transplant, as well
      as the standardisation of techniques for partial liver resection. These
      guidelines should not be seen as final, but rather as a starting point for
      further discussion between the various national and international liver tumour
      study groups.

PMID- 15862753
TI  - GG genotype of cyclin D1 G870A polymorphism is associated with increased risk and
      advanced colorectal cancer in patients in Singapore.
AB  - Recent studies have implicated cyclin D1 G870A single-nucleotide polymorphism
      (SNP) in susceptibility to and early onset of colorectal cancers (CRC). We
      investigated the role of cyclin D1 G870A SNP in Singapore CRC patients without
      dominant family history by genotyping 254 patients and 101 controls. The risk of
      cancer for AA individuals was less than half that of GG individuals (odds ratio
      (OR) 0.41; 95% confidence interval (CI) 0.18-0.96). Furthermore, AA and AG
      patients whose tumours were Dukes C and D (OR 0.38; 95% CI 0.17-0.83), poorly
      differentiated (OR 0.28; 95% CI 0.09-0.84) and left-sided (OR 0.45; 95% CI 0.21
      0.98) were associated with significantly lower risk than GG patients. Young (aged
      50 years or less) GG patients had a 5-year lower mean age at onset than AA/AG
      patients (P=0.02). Young male GG patients had worse disease-specific survival
      than AA/AG patients (P=0.002). Thus, contrary to Caucasians, the GG (rather than
      AA) genotype is associated with increased susceptibility and advanced CRC in
      Singapore patients, suggesting a more complex relationship between the SNP and
      CRC risk, possibly modulated by population differences.

PMID- 15862754
TI  - In situ breast cancer: incidence trend and organised screening programmes in
      Italy.
AB  - The effect of mammography screening programmes on the incidence of in situ breast
      cancer (CIS) is described by analysis of the CIS incidence trend in the 1990s and
      comparison of pre-screening and screening periods in six areas of Italy. All 1069
      CIS arising in women aged 40-79 years between 1988 and 1999 were analysed through
      age-standardised rates and Poisson regression models. The results show that, for
      the whole series, ductal carcinoma in situ (DCIS) represented 89% and lobular
      carcinoma in situ (LCIS) 11% of CIS detected. For all six areas, the introduction
      of screening increased the incidence of DCIS (screening/pre-screening ratio,
      range 1.12-1.77). Overall, DCIS represented 11% (226/2022) of all screening
      detected cancers. A significant increasing trend in DCIS incidence during the
      1990s and a modification in pattern of age-specific incidence rates after the
      beginning of screening programmes were observed. This increase can largely be
      explained by screening programmes. The incidence observed during the screening
      period was a persistent 39% higher than during the pre-screening period, after
      adjustment for the "percentage of cases diagnosed by screening". The increase
      also involves women at an age not targeted by screening programmes. In
      conclusion, as the increasing trend in DCIS is not completely explained by the
      effect of the screening programmes, this supports the use of mammography as a
      "spontaneous" preventive practice during ongoing organised screening programmes,
      particularly among age groups not usually invited for screening. Therefore, the
      effect of mammography on stage-specific incidence of CIS may be more marked than
      expected on the basis of the effect of screening programmes.

PMID- 15862755
TI  - Independent prognostic effect of co-morbidity in lymphoma patients: results of
      the population-based Eindhoven Cancer Registry.
AB  - The prevalence of co-morbidity among elderly lymphoma patients is associated with
      a decrease in the use of chemotherapy. This study assessed the independent
      prognostic effect of co-morbidity in 1551 unselected lymphoma patients, diagnosed
      between 1995 and 2001 in the area of the population-based Eindhoven Cancer
      Registry. The prevalence of serious co-morbidity was 58% for patients with
      Hodgkin's disease (HD) who were over 60 years of age and 66% for patients with
      non-Hodgkin's lymphoma (NHL) who were over 60 years of age. The administration of
      chemotherapy declined in the presence of co-morbidity for elderly patients with
      early-stage HD and elderly patients with aggressive NHL. Co-morbidity was
      associated with a 10-20% decline in 5-year survival. Whether less frequent
      application of chemotherapy in the presence of co-morbidity is justified as far
      as complications, prognosis and quality of life are concerned requires further
      investigation.

PMID- 15862756
TI  - Identification of predictive factors for the occurrence of predisposing MLH1 and
      MSH2 germline mutations among Sardinian patients with colorectal carcinoma.
AB  - Factors predictive of carrying MLH1 and MSH2 germline mutations in patients with
      colorectal cancer (CRC) are as yet unknown. The aim of this population-based
      study, was to further define the role of MLH1/MSH2 mutations through an
      evaluation clinic program with 362 consecutive Sardinian CRC patients. Eight
      MLH1/MSH2 germline mutations were detected in 21 (6%) patients. Examining family
      cancer history, MLH1/MSH2 mutations were found in 14/48 (29.2%) probands from CRC
      families and, among them, in 10/13 (76.9%) families fulfilling the Amsterdam
      criteria. The patients with low familial recurrence (two CRCs in the family)
      presented a much lower frequency of MLH1/MSH2 mutations (2/55; 3.6%).
      Significantly higher rates of MLH1/MSH2 mutations were found in patients with age
      of onset 45 years (P=0.012) or with 3 affected family members (P=0.009). While no
      significant predictive value was found for the presence of endometrial cancer
      within the family, earlier age of diagnosis and/or familial CRC recurrence should
      be considered as strong predictors for the occurrence of MLH1/MSH2 mutations, and
      therefore useful in recommending CRC patients for genetic testing.

PMID- 15862757
TI  - Alphavbeta5-integrins mediate early steps of metastasis formation.
AB  - Tumour cell adhesion within the microvasculature of host organs, its
      stabilisation and cell invasion into the host organs, appear to be important
      steps in the formation of distant metastases. Intravital fluorescence-video
      microscopy was used to investigate the early steps in metastasis formation of
      colon carcinoma cells within the liver, which is the main target organ of
      colorectal carcinomas. The involvement of alphav-integrins was analysed in vivo
      using HT-29 cells after treatment with different function-blocking antibodies
      [pan-alphav (n=9 animals), specific alphavbeta3 (n=8 animals) and alphavbeta5
      (n=8 animals)] or linear Arg-Gly-Asp (RGD)-containing peptides (RGD-peptides)
      (n=6 animals). Treatment with anti-alphav and anti-alphavbeta5 antibodies
      resulted in significantly (P<0.001) decreased tumour cell adhesion in vivo within
      the hepatic microvasculature. Cells treated with anti-alphavbeta3 antibodies or
      unspecific immunoglobulin-G (IgG) did not show significant changes in their
      adhesive properties. Furthermore, inhibition of cell adhesion was achieved by
      linear RGD-peptides in a dose-dependent manner. Relative numbers of migrated
      cells were not affected by any of the treatments. These results suggest that
      alphav-integrins, especially alphavbeta5, can influence the ability of
      circulating tumour cells to adhere within the hepatic microvessels. In contrast,
      migration of adherent cells into the liver parenchyma was not affected by alphav
      integrin inhibition. Our findings support the hypothesis that specific
      interactions between circulating tumour cells and host organs are required for
      organ-specific tumour cell arrest.

PMID- 15862758
TI  - Long-term observation reveals time-course-dependent characteristics of tumour
      vascularisation.
AB  - Functional properties of tumour vasculature influence the process of metastasis
      and play a role in generating a heterogeneous metabolic microenvironment, which
      contributes to genetic instability and inefficiency of tumour therapies.
      Morphological and functional properties of tumour vasculature may vary from
      tumour onset to late-stage disease. The aim of this study was to identify the
      dynamic alteration in tumour microcirculation in a chronic observation model.
      Invasively-growing, non-disseminating, green fluorescent protein transfected,
      human bone marrow derived endothelial cells, were implanted into cranial windows
      of severe combined immunodeficient mice. Intravital fluorescence microscopy was
      performed over a period of 85 days to measure permeability, leucocyte-endothelial
      interaction (LEI) and tissue perfusion rate as functional parameters. Vessel
      density, branching pattern and scanning electron microscopy were monitored as
      morphological parameters. Concordant with an increasing count of transendothelial
      pores, the results show that the initial event following tumour cell implantation
      was a significant increase in the permeability of pre-existing vessels. The
      variations in newly formed vessels were characterised by sequentially-occurring
      functional and morphological alterations with the development of characteristics
      typical of tumour vessels, such as increased count of trifurcations and variation
      in vessel calibre by more than 100%. In parallel with the increasing vessel
      volume per area, the tissue perfusion rate increased until day 61. It is
      concluded from the step-specific sequential functional and morphological
      alterations that the efficiency of adjuvant therapies depends not only on their
      intrinsic efficiency but also on the timing of their initiation.

PMID- 15862759
TI  - Genomic changes identified by comparative genomic hybridisation in docetaxel
      resistant breast cancer cell lines.
AB  - Docetaxel is one of the most effective chemotherapeutic agents in the treatment
      of breast cancer. Breast cancers can have an inherent or acquired resistance to
      docetaxel but the causes of this resistance remain unclear. In this study high
      level, docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231)
      were created, and comparative genomic hybridisation was used to identify genomic
      regions associated with resistance to docetaxel. MCF-7 resistant cells showed an
      amplification of chromosomes 7q21.11-q22.1, 17q23-q24.3, 18, and deletion of
      chromosomes 6p, 10q11.2-qter and 12p. MDA-MB-231 resistant cells showed a gain of
      chromosomes 5p, 7q11.1-q35, 9, and loss of chromosomes 4, 8q24.1-qter, 10,
      11q23.1-qter, 12q15-q24.31, 14q and 18. Whole chromosome paints confirmed these
      findings. Amplification of 7q21 and loss of 10q may represent a common mechanism
      of acquired docetaxel resistance in breast cancer cells. This study is the first
      description of a genomic approach specifically to identify genomic regions
      involved in resistance to docetaxel.

PMID- 15862760
TI  - Malignant transformation of wild-type but not plasminogen activator inhibitor-1
      gene-deficient fibroblasts decreases cellular sensitivity to chemotherapy
      mediated apoptosis.
AB  - Plasminogen activator inhibitor-1 (PAI-1) inhibits the activation of the
      plasminogen activator system, the latter being involved in cancer growth and
      dissemination. Interestingly, PAI-1 is elevated in many solid tumours and this
      elevation has consistently been shown to be associated with shorter length of
      patient survival. This study aims to determine whether PAI-1 contributes to
      cancer cell growth by inhibiting apoptosis of tumour cells. It is shown that
      spontaneous transformation decreases cellular sensitivity to chemotherapy
      mediated apoptosis of wild-type, but not PAI-1 gene-deficient, fibrosarcomas. PAI
      1 gene-deficient and wild-type mice displayed similar sensitivity to treatment
      with etoposide, suggesting a differential effect of PAI-1 expression between
      cancer cells and normal cells. Thus, since PAI-1 appears to be an important
      factor in regulating apoptosis in cancer cells but not in normal cells,
      inhibitors of PAI-1 might be useful as sensitising pre-treatment for subsequent
      apoptosis-inducing anti-cancer therapy.

PMID- 15862761
TI  - Evaluation of Lipin 2 as a candidate gene for autosomal dominant 1 high-grade
      myopia.
AB  - The first autosomal dominant high-grade myopia locus has been mapped to
      chromosome 18p11.31 between markers D18S59 and D18S1138 by haplotype analysis.
      Refinement of the region by transmission disequilibrium testing suggests that a
      candidate gene (or genes) for this locus named myopia 2 (MYP2) is likely in an
      interval between markers D18S63 and D18S52. Lipin 2 (LPIN2), a candidate gene for
      lipodystrophy, maps in proximity to this locus. Our purpose in this study was to
      identify mutations and polymorphisms in the LPIN2 gene in myopic patients and
      control subjects. Expression studies of this gene by reverse transcription
      polymerase chain reaction (RT-PCR) showed that LPIN2 was ubiquitously expressed
      in various tissues, such as brain, kidney, lung, heart, and skeletal muscles. It
      was also expressed in cornea, lens, retina, optic nerve, and sclera. Direct
      sequencing of the LPIN2 gene revealed 11 single nucleotide polymorphisms (SNPs)
      in myopia and unaffected individuals. Eight of them were novel. Among the 11 SNPs
      detected in this study, 2 exonic variants (G2950692A and C2924436T) were
      synonymous and do not lead to changes in amino acid of the translated protein
      product. Two transversions in intron 1 (T2951033A homozygote and heterozygote,
      C2951049A) and one transversions in intron 7 (G2924536C homozygote and
      heterozygote), 5 nucleotide variants (A 2909606T, del2909343T, G2907798C,
      T2907425G, T2907152C) in the 3'-untranslated region (3'-UTR), and TATTAA
      nucleotide deletions (homozygote and heterozygote) at 2950970-5 in intron 1 were
      also detected. Although LPIN2 gene was excluded as a candidate for MYP2, the SNPs
      detected in this study will aid in future mapping and association studies
      involving this gene.

PMID- 15862762
TI  - Gene splice sites correlate with nucleosome positions.
AB  - Gene sequences in the vicinity of splice sites are found to possess dinucleotide
      periodicities, especially RR and YY, with the period close to the pitch of
      nucleosome DNA. This confirms previously reported findings about preferential
      positioning of splice junctions within the nucleosomes. The RR and YY
      dinucleotides oscillate counter-phase, i.e., their respective preferred positions
      are shifted about half-period from one another, as it was observed earlier for AA
      and TT dinucleotides. Species specificity of nucleosome positioning DNA pattern
      is indicated by the predominant use of the periodical GG(CC) dinucleotides in
      human and mouse genes, as opposed to predominant AA(TT) dinucleotides in
      Arabidopsis and C. elegans.

PMID- 15862763
TI  - Formation of [b(n-1) + OH + H]+ ion structural analogs by solution-phase
      chemistry.
AB  - Derivatization of a variety of peptides by a method known to enhance anhydride
      formation is demonstrated by mass spectrometry to yield ions that have elemental
      composition and fragmentation properties identical to [b(n-1) + OH + H]+ ions
      formed by gas-phase rearrangement and fragmentation. The [b(n-1) + OH + H]+ ions
      formed by gas-phase rearrangement and fragmentation and the solution-phase [b(n
      1) + OH + H]+ ion structural analogs formed by derivatization chemistry show two
      different forms of dissociation using multiple-collision CAD in a quadrupole ion
      trap and unimolecular decomposition in a TOF-TOF; one group yields identical
      product ions as a truncated form of the peptide with a free C-terminal carboxylic
      acid and fragments at the same activation energy; the other group fragments
      differently from the truncated peptide, being more resistant to fragmentation
      than the truncated peptide and yielding primarily the [b(n-2) + OH + H]+ product
      ion. Nonergodic electron capture dissociation MS/MS suggests that any structural
      differences between the specific-fragmenting [b(n-1) + OH + H]+ ions and the
      truncated peptide is at the C-terminus of the peptide. The specific-fragmentation
      can be readily observed by MS(n) experiments to occur in an iterative fashion,
      suggesting that the C-terminal structure of the original [b(n-1) + OH + H]+ ion
      is maintained after subsequent rearrangement and fragmentation events in peptides
      which fragment specifically. A mechanism for the formation of specific
      fragmenting and nonspecific-fragmenting [b(n-1) + OH + H]+ ions is proposed.

PMID- 15862764
TI  - Fragmentation of negative ions from carbohydrates: part 1. Use of nitrate and
      other anionic adducts for the production of negative ion electrospray spectra
      from N-linked carbohydrates.
AB  - Negative ion spectra of N-linked glycans were produced by electrospray from a
      dilute solution of the glycans and various salts in methanol:water using a Waters
      Micromass Q-TOF Ultima Global tandem quadrupole/time-of-flight (Q-TOF) mass
      spectrometer. Stable anionic adducts were formed with chloride, bromide, iodide,
      nitrate, sulphate, and phosphate. Unstable adducts that fragmented by a cross
      ring cleavage of the reducing N-acetylglucosamine (GlcNAc) residue, were formed
      with fluoride, nitride, sulphide, carbonate, bicarbonate, hydroxide, and acetate.
      Nitrate adducts prepared from ammonium nitrate produced the most satisfactory
      spectra as they were relatively free from in-source fragmentation products and
      gave signals that were about ten times as strong as those from corresponding [M -
      H]- ions prepared from solutions containing ammonium hydroxide. Detection limits
      were in the region of 20 fmol. Neutral glycans gave both singly- and doubly
      charged ions with the larger glycans preferring the formation of doubly-charged
      ions. Acidic glycans with several acidic groups gave ions in higher charge states
      as the result of ionization of the anionic groups. Low energy collision-induced
      decomposition (CID) spectra of the singly-charged ions were dominated by cross
      ring and C-type fragments, unlike the corresponding spectra of the positive ions
      that contained mainly B- and Y-type glycosidic fragments. Formation of these ions
      could be rationalized by proton abstraction from various hydroxy groups by an
      initially-formed anionic adduct. Prominent glycosidic and cross-ring cleavage
      ions defined structural features such as the specific composition of each of the
      two antennae, presence of a bisecting GlcNAc residue and location of fucose
      residues, details that were difficult to determine by conventional techniques.
      Acidic glycans fragmented differently on account of charge localization on the
      acid functions rather than the hydroxy groups.

PMID- 15862765
TI  - Fragmentation of negative ions from carbohydrates: part 2. Fragmentation of high
      mannose N-linked glycans.
AB  - [M + NO3]- And [M + (NO3)2]2- ions were produced by electrospray from neutral
      high-mannose ([Man](5-9)[GlcNAc]2, [Glc](1-3)[Man](4-9)[GlcNAc]2) N-linked
      glycans and their 2-aminobenzamide derivatives sprayed from methanol:water
      containing ammonium nitrate. Low energy collision-induced decomposition (CID)
      spectra of both types of ions were almost identical and dominated by cross-ring
      and C-type fragments, unlike the corresponding spectra of the positive ions that
      contained mainly B- and Y-type glycosidic fragments. This behavior could be
      rationalized by an initial proton abstraction from various hydroxy groups by the
      initially-formed anionic adduct. These negative ion spectra were more informative
      than the corresponding positive ion spectra and contained prominent ions that
      were diagnostic of structural features such as the composition of individual
      antennas that were not easily obtainable by other means. C-ions defined the
      sequence of the constituent monosaccharide residues. Detailed fragmentation
      mechanisms are proposed to account for many of the diagnostic ions.

PMID- 15862767
TI  - Separation of sodiated isobaric disaccharides and trisaccharides using
      electrospray ionization-atmospheric pressure ion mobility-time of flight mass
      spectrometry.
AB  - A series of isobaric disaccharide-alditols, four derived from O-linked
      glycoproteins, and select trisaccharides were rapidly resolved using tandem high
      resolution atmospheric pressure ion-mobility time-of-flight mass spectrometry.
      Electrospray ionization was used to create the gas-phase sodium adducts of each
      carbohydrate. Using this technique it was possible to separate up to three
      isobaric disaccharide alditols and three trisaccharides in the gas phase. Reduced
      mobility values and experimentally determined ion-neutral cross sections are
      reported for each sodium-carbohydrate complex. These studies demonstrated that
      ion mobility separations at atmospheric pressure can provide a high-resolution
      dimension for analysis of carbohydrate ions that is complementary to traditional
      mass spectral (m/z) ion analysis. Combining these independent principles for
      separation of ions provides a powerful new bioanalytical tool for the
      identification of isomeric carbohydrates.

PMID- 15862766
TI  - Fragmentation of negative ions from carbohydrates: part 3. Fragmentation of
      hybrid and complex N-linked glycans.
AB  - Hybrid and complex N-linked glycans were ionized by electrospray in the presence
      of ammonium nitrate to give [M + NO3]- and [M + (NO3)2]2- ions. Low energy
      collision-induced decomposition (CID) spectra of both types of ions were almost
      identical and were dominated by C-type glycosidic and cross-ring fragments,
      unlike the corresponding spectra of the positive ions that contained mainly B-
      and Y-type glycosidic fragments. Also, in contrast to fragments in the positive
      ion spectra, many of these ions appeared to be produced by single pathways
      following proton abstraction from specific hydroxy groups. Consequently, many
      ions were diagnostic for specific structural features. Such features included the
      composition of each of the two antennas, the presence or absence of a bisecting
      GlcNAc residue, and the location of fucose residues on the core GlcNAc residues
      and on the antennas. C-ions defined the sequence of the constituent
      monosaccharide residues. Detailed fragmentation mechanisms are proposed to
      account for several of the diagnostic ions.

PMID- 15862768
TI  - MALDI-TOF MS analysis of soluble PEG based multi-step synthetic reaction mixtures
      with automated detection of reaction failure.
AB  - Macromolecules of tunable solubility, used to mimic inert insoluble materials
      while maintaining solution conditions, allowed the performance of efficient
      supported organic chemistry and facilitated in situ reaction monitoring. To
      satisfy the high throughput requirements of automated synthetic processes,
      organic syntheses carried out on bifunctional polyethylene glycol polymers
      (PEG(3400)-OH) were monitored step-by-step by matrix assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF MS). A protocol was
      designed to control the ionization mechanism of such polymers exhibiting high
      affinity for alkali metal cations. Automated, rapid, and reliable data
      interpretation was performed by an in-house developed visual basic application
      relying on the sodiated ion accurate monoisotopic mass measurement. The
      methodology was illustrated through the monitoring of a six-step synthetic
      scheme.

PMID- 15862769
TI  - Ionic-liquid matrices for improved analysis of phospholipids by MALDI-TOF mass
      spectrometry.
AB  - The use of ionic liquid matrices (ILMs) for phospholipids (PLs) affords higher
      signal intensity, smaller spot size, improved spot homogeneity, better signal
      reproducibility, and comparable or better detection limits compared to that of
      the crystalline matrix 2,5-dihydroxybenzoic acid (2,5-DHB). The ionization
      products are comparable to those with 2,5-DHB although the use of ILMs gives a
      stronger tendency to produce alkali-metal-ion adducts and a lower extent of
      prompt fragmentation.

PMID- 15862770
TI  - Influence of the labeling group on ionization and fragmentation of carbohydrates
      in mass spectrometry.
AB  - The ionization and fragmentation behaviors of carbohydrate derivatives prepared
      by reaction with 2-aminobenzamide (AB), 1-phenyl-3-methyl-5-pyrazolone (PMP), and
      phenylhydrazine (PHN) were compared under identical mass spectrometric
      conditions. It has been shown that the intensities of signals in MS spectra
      depend on the kind of saccharides investigated and reducing end labels used. PMP
      sialyllactose, when ionized by ESI/MALDI, produced a mixture of [M + H]+, [M +
      Na]+, [M - H + 2Na]+ ions in the positive mode and [M - H]-, [M + Na - 2H]- ions
      in the negative mode. The AB and PHN derivatives formed abundant [M + H]+ and [M 
      H]- ions in ESI, and by matrix-assisted laser desorption/ionization (MALDI)
      produced abundant [M + Na]+ ions. PMP- and reduced AB-sialyllactose produced only
      Y-type fragment ions under both MS/MS sources. In the electrospray ionization
      (ESI)-MS/MS spectrum of PHN-sialyllactose, abundant ions corresponded to B, Z
      cleavages and in its MALDI-MS/MS spectrum, the abundant ions were consistent with
      Y glycosidic cleavages with the concurrence of B, C, and cross-ring fragment
      ions. In the MALDI-MS spectra of oligosaccharides acquired immediately after
      derivatization, it was possible to detect only PHN derivatives. After
      purification, spectra of all three types of derivatives showed high signal-to
      noise ratios with the most abundant ions observed for AB reduced saccharides. [M
      + Na]+ ions were the dominant products and their fragmentation patterns were
      influenced by the type of the labeling and the kind of oligosaccharide
      considered. In the MALDI-PSD and -MS/MS spectra of AB-derivatized glycans, higher
      m/z fragment ions corresponded to B and Y cleavages and the loss of bisecting
      GlcNAc appeared as a weak signal or was not detected at all. Fragmentation
      patterns observed in the spectra of hybrid/complex PHN and PMP glycans were more
      comparable-higher m/z fragments corresponded to B and C glycosidic cleavages. For
      PHN glycans, the abundance of ions resulting from the loss of bisecting GlcNAc
      depended on the number of residues linked to the 6-positioned mannose. Also, PHN
      and PMP derivatives produced cross-ring cleavages with abundances higher than
      observed in the spectra of AB derivatized oligosaccharides. For high-mannose
      glycans, the most informative cleavages were provided by AB and PHN type of
      labeling. Here, PMP produced dominant Y-cleavages from the chitobiose while other
      ions produced weak signals.

PMID- 15862771
TI  - Fluorotrimethylsilane affinities of anionic nucleophiles: a study of fluoride
      induced desilylation.
AB  - In this study, preparation and decomposition of five novel pentavalent
      fluorosiliconates, RSi(CH3)3F- (R = CH3CH2O, CF3CH2O, (CH3)2CHO, (CH3)3SiO, and
      (CH3)3SiNH) is used to investigate the process of fluoride-induced desilylation.
      The siliconates were characterized by collision-induced dissociation and energy
      resolved mass spectrometry. Decomposition of RSi(CH3)3F- leads to loss of the
      nucleophile R- and FSi(CH3)3, except in the case of (CH3)3SiNHSi(CH3)3F-, where
      HF loss is also observed. Ion affinities for FSi(CH3)3 have been measured for all
      five nucleophiles, and compare well with computational predictions. The observed
      trend of the bond dissociation energies resembles the trend of deltaH(acid)
      values for the corresponding conjugate acids, RH. Additionally, this data has
      been incorporated with existing thermochemistry to derive fluoride affinities for
      four of the silanes (R = CH3CH2O, (CH3)2CHO, (CH3)3SiO, and (CH3)3SiNH). We use
      the fluoride affinity of the silanes and the FSi(CH3)3 affinity of the departing
      nucleophilic anion to assess the feasibility of fluoride-induced desilylation of
      the silanes examined in this work.

PMID- 15862772
TI  - Low uncertainty reverse isotope dilution ICP-MS applied to certifying an
      isotopically enriched Cd candidate reference material: a case study.
AB  - An analytical method is presented based on reverse isotope dilution single
      detector inductively coupled plasma magnetic sector mass spectrometry (ID-ICP
      SMS) and applied to the specific case of the certification of a (111)Cd enriched
      candidate Cd spike calibration material (nominal mass fraction 10 mg kg(-1) in 5%
      HNO3 solution). Uncertainty propagation was used as a tool for both determining
      the analytical approach and validating it. The robustness of close to "exact
      matching" reverse IDMS to correction of measured isotope intensities for
      multiplicative (mass discrimination) and (semi)additive effects (dead time,
      instrumental background, and isobaric interference) is discussed. The very low
      experimental relative standard deviation of the mean (0.08%) of eight replicate
      determinations indicated that all significant sources of uncertainty had probably
      been taken into account for the estimation of the final combined uncertainty
      statement (U(c) = 0.17%, k = 1). IRMM-621 was used as comparator. Uncertainties
      on IUPAC isotopic abundances of 111Cd and 112Cd, for the natural Cd solution
      involved between the two enriched materials, formed nearly 60% of U(c). The
      repeatability of the isotope ratio measurements contributed less than 10%.
      Correction for procedural blank necessitated somewhat unusual calculations
      (potential contamination of an enriched material with natural Cd). The procedure
      also involved a quadrupole based ICP-MS judged to be appropriate for the
      characterization of the isotopic composition. For comparison purposes, direct
      IDMS results are simulated using identical experimental input data. Finally, a
      significant background signal in the 106-116 mass region, observed only with the
      magnetic sector instrument, was attributed to argon based isobaric interferences.

PMID- 15862773
TI  - Tandem mobility mass spectrometry study of electrosprayed tetraheptyl ammonium
      bromide clusters.
AB  - Multiply charged electrospray ions from concentrated solutions of Heptyl4N+Br-
      (designated A+B- hereafter) in formamide are analyzed mass spectrometrically (MS)
      following mobility selection in ambient air in a differential mobility analyzer
      (DMA). Most of the sharp mobility peaks seen are identified as (AB)(n)A+
      clusters, with 0 < or = n < ot = 5. One anomalously abundant and mobile ion is
      identified as NH4+(AB)4. Six ions in the (AB)n(A+)2 series are also identified,
      completing and correcting earlier mobility data for singly and doubly charged
      ions up to masses of almost 9000 Da. The more mobile of two broad humps seen in
      the mobility spectrum includes m/z values approximately from 2500 up to 12,000
      Da. It is formed primarily by multiply charged (AB)n(A+)z clusters with multiple
      ammonium bromide adducts. Because of overlapping of many peaks of different m/z
      and charge state z, only a few individual species can be identified by MS alone
      in this highly congested region. However, the spectral simplification brought
      about by mobility selection upstream of the MS reveals a series of broad
      modulations in m/z space, with all ions resolved in the second, third, ...sixth
      modulation being in charge states z = 2, 3, ...6, respectively. Extrapolation of
      this trend beyond the sixth wave fixes the ion charge state (in some cases up to
      z = 15) and mass (beyond m = 175,000 u). This wavy structure had been previously
      observed and explained in terms of ion evaporation kinetics from volatile drops,
      though without mass identification. All observations indicate that the clusters
      are formed as charged residues, but their charge state is fixed by the Iribarne
      Thomson ion evaporation mechanism. Consequently, the measured curve of cluster
      diameter versus z yields the two parameters governing ion evaporation kinetics.
      Clusters with z > 1 and electrical mobility Z > 0.495 cm2/V/s are metastable and
      evaporate a singly charged cluster, probably (AB)2A+, between the DMA and the MS.
      Plotting the electrical mobilities Z of the clusters in the form (z/Z)1/2 versus
      m(1/3) (both proportional to cluster diameter) collapse the data for all cluster
      sizes and charge states into one single straight line for Z below 0.495 cm2/V/s.
      This linear relation reveals a uniform apparent cluster density of 0.935 g/cm3
      and an effective hard-sphere diameter of the air molecules of 0.44 nm. An
      anomalous mobility increase is observed at diameters below 3 nm.

PMID- 15862774
TI  - An investigation of enhanced secondary ion emission under Au(n)+ (n = 1-7)
      bombardment.
AB  - We investigate the mechanism of the nonlinear secondary ion yield enhancement
      using Au(n)+ (n = 1, 2, 3, 5, 7) primary ions bombarding thin films of Irganox
      1010, DL-phenylalanine and polystyrene on Si, Al, and Ag substrates. The largest
      differences in secondary ion yields are found using Au+, Au2+, and Au3+ primary
      ion beams. A smaller increase in secondary ion yield is observed using Au5+ and
      Au7+ primary ions. The yield enhancement is found to be larger on Si than on Al,
      while the ion yield is smaller using an Au+ beam on Si than on Al. Using Au(n)+
      ion structures obtained from Density Functional Theory, we demonstrate that the
      secondary yield enhancement is not simply due to an increase in energy per area
      deposited into the surface (energy deposition density). Instead, based on simple
      mechanical arguments and molecular dynamics results from Medvedeva et al, we
      suggest a mechanism for nonlinear secondary ion yield enhancement wherein the
      action of multiple concerted Au impacts leads to efficient energy transfer to
      substrate atoms in the near surface region and an increase in the number of
      secondary ions ejected from the surface. Such concerted impacts involve one, two,
      or three Au atoms, which explains well the large nonlinear yield enhancements
      observed going from Au+ to Au2+ to Au3+ primary ions. This model is also able to
      explain the observed substrate effect. For an Au+ ion passing through the more
      open Si surface, it contacts fewer substrate atoms than in the more dense Al
      surface. Less energy is deposited in the Si surface region by the Au+ primary ion
      and the secondary ion yield will be lower for adsorbates on Si than on Al. In the
      case of Au(n)+ the greater density of Al leads to earlier break-up of the primary
      ion and a consequent reduction in energy transfer to the near-surface region when
      compared with Si. This results in higher secondary ion yields and yield
      enhancements on silicon than aluminum substrates.

PMID- 15862775
TI  - Comparison of the effects of ionization mechanism, analyte concentration, and ion
      "cool-times" on the internal energies of peptide ions produced by electrospray
      and atmospheric pressure matrix-assisted laser desorption ionization.
AB  - The propensities of a series of peptide ions produced by both electrospray and
      atmospheric pressure matrix assisted laser desorption ionization (AP-MALDI) to
      fragment in an ion trap mass spectrometer under various conditions were studied
      in detail by measuring the extent of fragmentation of precursor ions by collision
      induced dissociation (CID) as a function of applied resonance excitation RF
      voltage. For the most basic peptides, the energy required to fragment MH+ ions
      generated by electrospray exceeded that required to fragment equivalent AP-MALDI
      ions under identical instrumental conditions; the reverse was observed for a
      peptide incorporating no basic residues, while peptides of intermediate basicity
      showed little difference between the ionization methods. This correlation between
      peptide basicity and the difference in the energy required to induce
      fragmentation of MH+ ions generated by AP-MALDI and electrospray is attributed
      primarily to a trend in the internal energies of the ions generated by AP-MALDI
      (the greater the difference in gas-phase basicities between the matrix and the
      analyte the greater the internal energy of the analyte ions produced).
      Furthermore the internal energies of ions produced by AP-MALDI, but not the
      equivalent ions formed by electrospray, were observed to decrease with decreasing
      analyte concentration. We attribute this finding to the cooling effect of
      endothermic dissociation of analyte ion/matrix molecule clusters following the
      matrix assisted laser desorption step. Time-resolved analyses (measurement of
      extent of fragmentation of precursor ions by CID as a function of pre-CID "cool
      times") revealed that cooling periods in excess of 250 ms were required to
      achieve internal energy equilibrium through cooling collisions with the helium
      buffer gas. Furthermore, these analyses demonstrated that, even after these
      extended cooling times, equivalent ions formed by the two ionization techniques
      showed different propensities to fragment. We conclude that the two different
      ionization techniques produce ion populations that may differ in their three
      dimensional structure.

PMID- 15862776
TI  - Structural characterization of the GM1 ganglioside by infrared multiphoton
      dissociation, electron capture dissociation, and electron detachment dissociation
      electrospray ionization FT-ICR MS/MS.
AB  - Gangliosides play important biological roles and structural characterization of
      both the carbohydrate and the lipid moieties is important. The FT-ICR MS/MS
      techniques of electron capture dissociation (ECD), electron detachment
      dissociation (EDD), and infrared multiphoton dissociation (IRMPD) provide
      extensive fragmentation of the protonated and deprotonated GM1 ganglioside. ECD
      provides extensive structural information, including identification of both
      halves of the ceramide and cleavage of the acetyl moiety of the N-acetylated
      sugars. IRMPD provides similar glycan fragmentation but no cleavage of the acetyl
      moiety. Cleavage between the fatty acid and the long-chain base of the ceramide
      moiety is seen in negative-ion IRMPD but not in positive-ion IRMPD of GM1.
      Furthermore, this extent of fragmentation requires a range of laser powers,
      whereas all information is available from a single ECD experiment. However,
      stepwise fragmentation by IRMPD may be used to map the relative labilities for a
      series of cleavages. EDD provides the alternative of electron-induced
      fragmentation for negative ions with extensive fragmentation, but suffers from
      low efficiency as well as complication of data analysis by frequent loss of
      hydrogen atoms. We also show that analysis of MS/MS data for glycolipids is
      greatly simplified by classification of product ion masses to specific regions of
      the ganglioside based solely on mass defect graphical analysis.

PMID- 15862777
TI  - Facile generation of tripeptide radical cations in vacuo via intramolecular
      electron transfer in Cu(II) tripeptide complexes containing sterically encumbered
      terpyridine ligands.
AB  - Molecular radical cations of tripeptides of the form glycylglycyl(residue X)
      (GGX*+) are produced by the collision-induced, intramolecular one-electron
      transfer of [Cu(II)(L)GGX]*2+ complexes (L = triamine ligand). We demonstrate,
      for the first time, the formation of molecular radical cations of all of the
      aliphatic, basic, aromatic, acidic, and some heteroatom-bearing GGX tripeptides,
      albeit inefficiently in some cases, by altering the structure of the auxiliary
      polyamine ligand bound to the copper atom. The design of the ligand allows
      exquisite control over the nature of the dissociation pathway. Steric hindrance
      of bulky groups in the ligand affects the binding of the peptide to the copper
      ion; this interaction is an important factor in determining whether the electron
      transfer pathway predominates.

PMID- 15862778
TI  - Leveling response factors in the electrospray ionization process using a heated
      capillary interface.
AB  - Several investigators have observed a discrepancy in electrospray response of
      complementary strands from denatured DNA, which has been attributed to the
      difference in hydrophobicity between the two strands; the more hydrophobic
      species tend to have higher ion abundances. The implementation of a heated
      electrospray source has allowed us to "level" the electrospray response for two
      equimolar complementary strands with different hydrophobicities. As the
      temperature was increased, the ratio of ion abundances of the less hydrophobic
      noncoding strand to the more hydrophobic coding strand approached unity.
      Furthermore, the heated electrospray source was used to denature amplicons
      containing 7-deaza purines, which can be used to facilitate sequencing by mass
      spectrometry.

PMID- 15862779
TI  - A comparison of data analysis methods for determining gas phase stabilities by
      CID: alkali metal complexes of polyether ionophore antibiotics.
AB  - The gas phase stabilities of Group I metal complexes of the polyether ionophore
      antibiotics lasalocid and monensin were investigated by collision induced
      dissociation mass spectrometry. Electrospray ionization was used with a triple
      quadrupole mass spectrometer for the determination of threshold dissociation
      energies upon application of increasing collision energies. Various data analysis
      techniques for the determination of dissociation energies are discussed to assess
      the most suitable method for determining the stabilities of the ionophore-metal
      complexes studied here. In all cases only the relative stabilities of different
      complexes may be obtained by the method presented in this study, which does not
      assess absolute gas phase dissociation energies. Correction factors have been
      applied, however, to account for the energy conversion during collisions of
      different metal complexes and the varying degrees of freedom of different sized
      ligands, allowing for the comparison of the stabilities of different ionophores
      with like-metals. The measured threshold dissociation energies were compared with
      respect to the ionic radius of the metal cation, revealing a maximum stability
      for the K+ complexes of both lasalocid and monensin. A striking decrease in the
      stabilities of the Rb+ and Cs+ complexes was observed and is believed to be
      related to a decreasing degree of coordination that the ionophores can accomplish
      with the larger metals.

PMID- 15862780
TI  - Isolation and partial characterization of a 30 kDa adhesin from Paracoccidioides
      brasiliensis.
AB  - The virulence of Paracoccidioides brasiliensis can be attenuated or lost after
      long periods of repeated subculturing and reestablished after animal inoculation.
      Only one adhesin (gp43) has been described until now, among the various
      identified components of P. brasiliensis, and gp43 shows adhesion to laminin.
      Thus, the present study was designed to isolate and characterize factors
      putatively related to the capacity of this fungus to adhere to the host by
      comparing P. brasiliensis samples, taken before and after animal inoculation. The
      two samples differed in their pattern of adhesion and invasion. The sample
      recently isolated from animals (Pb18b) demonstrated a greater capacity to adhere
      and to invade the Vero cells than the one subcultured in vitro (Pb18a). Extract
      from Pb18b also showed higher levels of protein expression than that from Pb18a,
      when two-dimensional electrophoresis gels were compared. A protein species of 30
      kDa, pI 4.9, was more evident in the Pb18b extract and had properties of adhesin.
      Laminin, but none of the other extracellular matrix (ECM) components, such as
      fibronectin, collagen I and IV, bound specifically to the P. brasiliensis 30 kDa
      protein. The roles of 30 kDa and gp43 in cellular interactions were investigated
      and the adhesion of P. brasiliensis yeast cells was intensively inhibited by pre
      treatment of epithelial cells with 30 kDa protein and gp43. Thus, this study
      presents evidence that adhesion capacity could be related to virulence, and that
      a 30 kDa adhesin accumulated differentially in samples with different levels of
      pathogenicity. This protein and its adhesion characteristics are being published
      for the first time and may be related to the virulence of P. brasiliensis.

PMID- 15862781
TI  - In vitro differentiation of mouse bone marrow mononuclear cells into hepatocyte
      like cells.
AB  - AIM: : It is imperative to explore some ways to gain the functional hepatocytes
      for hepatocyte transplantation. Bone marrow stem cells can differentiate into
      hepatocytes in vivo and in vitro. We select fibroblast growth factor-4 (FGF-4),
      oncostatin M (OSM), hepatocyte growth factor (HGF) and epithermal growth factor
      (EGF) as differentiation factors, and design the appropriate directed
      differentiation medium in order to gain hepatocytes through directed
      differentiation of bone marrow stem cells. METHODS: : Bone marrow mononuclear
      cells (BMMCs) were cultured in the directed differentiation media including FGF
      4, OSM, HGF and EGF. In the course of cell differentiation, cell morphology was
      observed, and the expression patterns of some genes of the hepatocyte were
      validated and confirmed by RT-PCR. The ALB-, and CK18-expressed cells were gone
      further step to be confirmed by Western blot analysis, immunofluorescence and
      flow cytometric analysis. Hepatocyte functional activity, including glycogen
      synthesis and urea production, were confirmed by periodic acid-Shiff (PAS)
      staining and urea assay. RESULTS: : Some epithelial-like cells or polygonal cells
      appeared in the directed differentiation medium within 12 days, and the number
      and sizes of colonies of epithelial-like cells or polygonal cells increased in
      the course of the cell directed differentiation. AFP, HNF-3ss, ALB and CK18 mRNA
      expressions first appeared within day 7, and lasted throughout the later directed
      differentiation. TTR, G-6-P and TAT mRNA expressions could be detected within day
      14, and their expressions lasted in the course of the later directed
      differentiation. ALB and CK18 were confirmed to exist in the differentiated BMMCs
      by Western blot analysis. ALB was found in the cytoplasm and cell membrane, while
      CK18 scattered in the cytoplasm by immunofluorescent staining. On day 21,the
      ratio of ALB-positive cells was 69.45%, and the ratio of CK18-positive cells was
      67.36%. The accumulation of glucogen was detected in the cytoplasm of the
      differentiated cells. The directed differentiated BMMCs produced urea 3 days
      later, and they produced urea in a time-dependent manner. CONCLUSIONS: : BMMCs
      could differentiate into hepatocytes or hepatocyte-like cells in the
      differentiation media including HGF, FGF-4, EGF, and OSM. These hepatocyte-like
      cells were identified at the gene level and protein level. Furthermore, these
      hepatocyte-like cells had some hepatocellular synthesis and metabolism functions.

PMID- 15862782
TI  - Prevention of hepatocellular carcinoma in chronic hepatitis B.

PMID- 15862783
TI  - Naris occlusion alters olfactory marker protein immunoreactivity in olfactory
      epithelium.
AB  - Though its function remains obscure, olfactory marker protein (OMP) has been
      implicated in olfactory transduction and the enhancement of neurogenesis within
      olfactory epithelium. Here we show, using Western blot analysis and
      immunocytochemistry, that unilateral naris occlusion (UNO) on postnatal day 1
      alters OMP immunoreactivity (IR) differentially on the occluded and non-occluded
      sides of the nasal cavity in 18, 24 and 70-day-old mice. Compared to untreated
      animals, UNO-treated animals had a decrease in OMP-IR in olfactory receptor
      neurons on the non-occluded side and an increase in OMP-IR in olfactory receptor
      neurons on the occluded side of the nasal cavity. These results suggest that OMP
      concentration is up- or down-regulated depending on the amount of odor
      stimulation olfactory receptor neurons receive. It is proposed that this apparent
      change in protein concentration may be part of a more general compensatory
      response by olfactory neurons to levels of odor in the environment.

PMID- 15862784
TI  - Minocycline inhibits oxidative stress and decreases in vitro and in vivo ischemic
      neuronal damage.
AB  - The neuroprotective effects of minocycline-which is broadly protective in
      neurologic-disease models featuring cell death and is being evaluated in clinical
      trials-were investigated both in vitro and in vivo. For the in vivo study, focal
      cerebral ischemia was induced by permanent middle cerebral artery occlusion in
      mice. Minocycline at 90 mg/kg intraperitoneally administered 60 min before or 30
      min after (but not 4 h after) the occlusion reduced infarction, brain swelling,
      and neurologic deficits at 24 h after the occlusion. For the in vitro studies, we
      used cortical-neuron cultures from rat fetuses in which neurotoxicity was induced
      by 24-h exposure to 500 microM glutamate. Furthermore, the effects of minocycline
      on oxidative stress [such as lipid peroxidation in mouse forebrain homogenates
      and free radical-scavenging activity against diphenyl-p-picrylhydrazyl (DPPH)]
      were evaluated to clarify the underlying mechanism. Minocycline significantly
      inhibited glutamate-induced cell death at 2 microM and lipid peroxidation and
      free radical scavenging at 0.2 and 2 microM, respectively. These findings
      indicate that minocycline has neuroprotective effects in vivo against permanent
      focal cerebral ischemia and in vitro against glutamate-induced cell death and
      that an inhibition of oxidative stress by minocycline may be partly responsible
      for these effects.

PMID- 15862785
TI  - Involvement of serotoninergic receptors in the anteroventral preoptic region on
      hypoxia-induced hypothermia.
AB  - Hypoxia causes a regulated decrease in body temperature (Tb). There is
      circumstantial evidence that the neurotransmitter serotonin (5-HT) in the
      anteroventral preoptic region (AVPO) mediates this response. However, which 5-HT
      receptor(s) is (are) involved in this response has not been assessed. Thus, we
      investigated the participation of the 5-HT receptors (5-HT1, 5-HT2, and 5-HT7) in
      the AVPO in hypoxic hypothermia. To this end, Tb of conscious Wistar rats was
      monitored by biotelemetry before and after intra-AVPO microinjection of
      methysergide (a 5-HT1 and 5-HT2 receptor antagonist, 0.2 and 2 microg/100 nL),
      WAY-100635 (a 5-HT(1A) receptor antagonist, 0.3 and 3 microg/100 nL), and SB
      269970 (a 5-HT7 receptor antagonist, 0.4 and 4 micro/100 nL), followed by 60 min
      of hypoxia exposure (7% O2). During the experiments, the mean chamber temperature
      was 24.6 +/- 0.7 degrees C (mean +/- SE) and the mean room temperature was 23.5
      +/- 0.8 degrees C (mean +/- SE). Intra-AVPO microinjection of vehicle or 5-HT
      antagonists did not change Tb during normoxic conditions. Exposure of rats to 7%
      of inspired oxygen evoked typical hypoxia-induced hypothermia after vehicle
      microinjection, which was not affected by both doses of methysergide. However,
      WAY-100635 and SB-269970 treatment attenuated the drop in Tb in response to
      hypoxia. The effect was more pronounced with the 5-HT7 antagonist since both
      doses (0.4 and 4 microg/0.1 microL) were capable of attenuating the hypothermic
      response. As to the 5-HT(1A) antagonist, the attenuation of hypoxia-induced
      hypothermia was only observed at the higher dose. Therefore, the present results
      are consistent with the notion that 5-HT acts on both 5-HT(1A) and 5-HT7
      receptors in the AVPO to induce hypothermia, during hypoxia.

PMID- 15862786
TI  - Fluoxetine and recovery of motor function after focal ischemia in rats.
AB  - Neuroprotective therapies and tissue plasminogen activator (t-PA) have limited
      application for most stroke patients and thus rehabilitation is the primary
      treatment option for improving recovery of function. Following brain injury,
      environmental enrichment, pharmacological and rehabilitative treatments can
      markedly alter neuronal plasticity and behavioral recovery even when delayed by
      several weeks after the insult. Fluoxetine has been given to stroke patients to
      combat depression but its effects on recovery of function are not known.
      Functional magnetic resonance imaging reveals that fluoxetine alters brain
      activity and modulates motor performance in stroke patients in a use-dependent
      fashion. Several antidepressants, including fluoxetine, increase growth factors
      and other proteins associated with plasticity, such as brain-derived neurotrophic
      factor (BDNF). In this study, we examined whether chronic administration of
      fluoxetine combined with rehabilitation affected recovery of function on 3
      separate tests of forelimb reaching, preference and limb coordination after focal
      ischemia in rats. Ischemia was induced in male Long-Evans rats by intracortical
      and striatal injections of endothelin-1. Fluoxetine (10 mg/kg/day) combined with
      rehabilitation therapy (6 h/day) for 4 weeks did not alter the degree or rate of
      recovery of function compared to non-treated animals. Despite the ability of
      fluoxetine to alter brain activity and increase growth factors, it does not
      appear to be an effective pharmacological adjunct to functional recovery after
      ischemia in rats.

PMID- 15862787
TI  - Functional linkage of H+/peptide transporter PEPT2 and Na+/H+ exchanger in
      primary cultures of astrocytes from mouse cerebral cortex.
AB  - In our previous studies, we demonstrated that the high-affinity type peptide
      transporter PEPT2 is expressed in rat cerebral cortex using synaptosomal membrane
      study and that the uptake of dipeptide [14C]glycylsarcosine into synaptosomes was
      stimulated by an inwardly directed H+ gradient (Fujita et al., Brain Res. 972, 52
      61, 2004). However, there is no information available for the driving force of
      PEPT2 function in the nervous system. In the present study, we investigated
      functional characteristics of PEPT2 mediated transport of Gly-Sar in primary
      cultured astrocytes from mouse cerebral cortex and examined the effects of Na+/H+
      exchanger (NHE) inhibitor on Gly-Sar uptake in mouse astrocytes. In mouse
      astrocytes, extracellular H+ influenced only the maximal velocity (Vmax) of Gly
      Sar uptake without affecting the apparent affinity (Kt). Interestingly, removal
      of Na+ from uptake buffer significantly reduced Gly-Sar uptake and Gly-Sar uptake
      was modulated by NHE inhibitors. The treatment of EIPA, an NHE inhibitor, altered
      the Vmax value of Gly-Sar uptake but had no effect on its Kt value. RT-PCR
      revealed that NHE1 and NHE2 mRNA are expressed in mouse cerebrocortical
      astrocytes. These results demonstrated that NHE activity is required to allow
      optimal uptake of dipeptides mediated by PEPT2 into the astrocytes. This study
      represents the first description of the functional co-operation of PEPT2 and NHE1
      and/or NHE2 in cerebrocortical astrocytes.

PMID- 15862788
TI  - Tetrodotoxin inactivation of pontine regions: influence on sleep-wake states.
AB  - Studies using various methodologies have implicated n. reticularis pontis oralis
      (RPO) and n. subcoeruleus (SubC) in the generation of rapid eye movement sleep
      (REM). In rats, electrolytic lesions in these regions may give rise to the
      phenomenon of REM without atonia (REM-A), in which the electrophysiological
      features of REM are normal except that atonia is absent and elaborate behaviors
      may be exhibited. However, electrolytic lesions damage both cell bodies and
      fibers of passage, and the neural reorganization and adaptation that can occur
      post-lesion can complicate interpretation. Tetrodotoxin (TTX) is a sodium channel
      blocker that temporarily inactivates both neurons and fibers of passage and thus
      may be functionally equivalent to an electrolytic lesion, but without allowing
      time for neural adaptation. In this study, we examined the influence of
      microinjections of TTX into RPO and SubC on sleep in freely behaving rats. Rats
      (90 day old male Sprague-Dawley) were implanted with electrodes for recording EEG
      and EMG. Guide cannulae were implanted aimed into RPO or SubC. Each animal
      received one unilateral microinjection (TTXUH: 5.0 ng/0.2 microl) and two
      bilateral microinjections (TTXBL: 2.5 ng/0.1 microl; TTXBH: 5.0 ng/0.2 microl) of
      TTX, and control microinjections of saline alone (SAL). The injections were made
      2 h following lights on, and sleep was recorded for the subsequent 22 h. Sleep
      was scored from computerized records in 10 s epochs. Recordings from the 10-h
      light period and the 12-h dark period were examined separately. TTX inactivation
      of RPO could decrease REM and non-REM (NREM), whereas inactivation of SubC
      produced relatively more specific decreases in REM with smaller effects on NREM.
      The results complement studies that have implicated RPO and SubC in REM
      generation. REM-A was not observed, suggesting that REM-A is a complex phenomenon
      that requires time for reorganization of the nervous system after insult.

PMID- 15862789
TI  - Calcium/calmodulin-dependent protein kinase II activity and expression are
      altered in the hippocampus of Pb2+-exposed rats.
AB  - In the present study, we examined whether calcium/calmodulin-dependent protein
      kinase II (CaMKII) is affected by chronic developmental Pb2+ exposure. The
      effects of Pb2+ exposure on rat hippocampal CaMKII were assessed by measuring
      CaMKII activity, phosphorylation of CaMKII at threonine-286, and CaMKII alpha and
      beta protein levels. In the hippocampus of Pb2+-exposed 50-day-old rats known to
      exhibit deficits in hippocampal long-term potentiation (LTP) and spatial
      learning, there was a marked reduction (41%) in the apparent maximal velocity
      (Vmax) of CaMKII and a significant increase (22%) in apparent affinity of the
      enzyme. These Pb2+-induced changes in CaMKII activity could not be explained by
      changes in enzyme phosphorylation at threonine-286 or sensitivity to calmodulin.
      In vitro incubation of hippocampal homogenates from control rats, but not from
      Pb2+-exposed rats, with Pb2+ prior to assay recapitulated the increase in the
      affinity of the enzyme observed with in vivo exposure to Pb2+. Western blots of
      cytosolic and membrane fractions from hippocampus showed a significant decrease
      in the levels of CaMKII-beta but not alpha protein in the cytosolic fraction of
      Pb2+-exposed rats. These findings indicate effects of developmental Pb2+ exposure
      on CaMKII, a component of calcium signaling associated with synaptic plasticity,
      learning, and memory.

PMID- 15862790
TI  - Functional analysis of the role of the median raphe as a regulator of hamster
      circadian system sensitivity to light.
AB  - The retinohypothalamic tract, a monosynaptic retinal projection to the
      suprachiasmatic nucleus (SCN), is the path by which light entrains the circadian
      system to the external photoperiod. Serotonergic neurons in the mesencephalic
      median raphe nucleus (MnR) also give rise to a major SCN afferent projection. The
      present study was designed to determine the extent to which MnR serotonergic
      projections regulate sensitivity of the circadian rhythm system to light.
      Serotonergic neurons in the MnR were destroyed by the direct application of the
      neurotoxin, 5,7-dihydroxytryptamine. Animals in constant darkness were given 5
      min white light pulses at circadian time 19. Light intensity varied from 0.0011
      to 70 microW/cm2. Assessment of rhythm phase response to light by lesioned and
      control animals revealed that animals lacking the MnR serotonergic projection are
      considerably more sensitive to light at high irradiances. The results are
      consistent with behavioral and physiological evidence implicating serotonin as an
      inhibitory modulator of the effects of light on circadian rhythmicity.

PMID- 15862791
TI  - The effect of sub-chronic nandrolone decanoate treatment on dopaminergic and
      serotonergic neuronal systems in the brains of rats.
AB  - Anabolic-androgenic steroids (AASs) are widely abused by adolescents, although
      persistent AAS use can cause several adverse physical and mental effects,
      including drug dependence. The first aim of the present study was to study the
      action of nandrolone decanoate on dopaminergic and serotonergic activities in the
      brains of rats. In order to evaluate the anabolic or toxic effects of the dosing
      regimens used, selected peripheral effects were monitored as well. Male Wistar
      rats were treated for 2 weeks. Injections containing nandrolone (5 and 20 mg/kg,
      i.m.) or vehicle were given once daily, 5 days a week. The levels of dopamine
      (DA), 5-hydroxytryptamine (5-HT) and their metabolites were assayed from
      dissected brain regions 3 days after the last injection. Blood was collected for
      chemical assays before, after 1 week treatment and at decapitation. Both doses of
      nandrolone significantly increased the levels of 3,4-dihydroxyphenylacetic acid
      (DOPAC), a metabolite of DA in the cerebral cortex, and the higher dose of
      nandrolone increased the concentrations of 5-HT in the cerebral cortex compared
      with the vehicle. In addition, after nandrolone treatment, the levels of
      hemoglobin and erythrocytes increased, and reticulocyte levels decreased. The
      results suggest that nandrolone at supraphysiological doses, high enough to
      induce erythropoiesis, induces changes in the dopaminergic and serotonergic
      neuronal system in the brains of rats. These phenomena may account to some of the
      observed central stimulatory properties that have been reported following AAS
      abuse.

PMID- 15862792
TI  - Spinal orexin-1 receptors mediate anti-hyperalgesic effects of intrathecally
      administered orexins in diabetic neuropathic pain model rats.
AB  - Orexin-A and orexin-B are endogenous ligands of orexin receptors that contain
      orexin-1 and orexin-2. Activation of the orexinergic system can produce
      antinociceptive effects in acute inflammatory, mono-neuropathic, and
      postoperative pain animal models, though the effects of orexins on diabetic
      neuropathic pain have not been previously investigated. In this study, we studied
      the anti-hyperalgesic effects of intrathecally administered orexins in a
      streptozotocin-induced diabetic rat. First, dose-dependent effects were
      investigated by measuring hind paw withdrawal thresholds in response to noxious
      heat and punctate stimuli, after which orexin levels in the cerebrospinal fluid
      of diabetic rats were measured and compared with those of normal rats using a
      radioimmunoassay method. The functional role of spinal orexin-1 receptors with
      the anti-hyperalgesic effects of orexins was also investigated using intrathecal
      pretreatment with SB-334867, a selective orexin-1 receptor antagonist.
      Intrathecally administered orexins produced an antinociceptive effect in diabetic
      rats, however, not in normal rats, though the orexin levels in the cerebrospinal
      fluid of diabetic rats were similar to those in normal rats. In addition, the
      anti-hyperalgesic effects of orexins were significantly inhibited by pretreatment
      with SB-334867. These findings demonstrate that the anti-hyperalgesic effects of
      orexins in diabetic rats are unlikely due to any direct effect by the supplement
      on decreased endogenous orexins in the cerebrospinal fluid and that orexin-1
      receptors in the spinal cord may be involved in the modulation of nociceptive
      transmission in diabetic neuropathy. We conclude that the spinal orexinergic
      system may be a possible target for elucidating the mechanisms of diabetes
      induced hyperalgesia.

PMID- 15862793
TI  - Effects of pertussis toxin on electroacupuncture-produced anti-hyperalgesia in
      inflamed rats.
AB  - Our previous study showed that electroacupuncture (EA) significantly attenuated
      hyperalgesia in an animal model of persistent inflammatory pain. The present
      study was designed to show if Gi/o protein is involved in EA-produced anti
      hyperalgesia. Spinal Gi/o-protein function was destroyed by intrathecal
      pretreatment with pertussis toxin (PTX). Seven days after the placement of an
      intrathecal PE-10 tube, PTX was injected into the intrathecal space of the lumbar
      spinal cord of rats. Seven days after PTX, complete Freund's adjuvant (CFA) was
      injected into the plantar surface of one hind paw of the rat to induce
      hyperalgesia in the injected paw. EA treatment was given at acupoint GB30
      immediately post-CFA and then hyperalgesia was assessed by measuring the degree
      of decreased paw withdrawal latency (PWL) to a noxious thermal stimulus. The
      results showed that PTX pretreatment prevented EA-produced anti-hyperalgesia in
      the CFA inflammatory pain model but did not affect either baseline pain threshold
      or CFA-induced hyperalgesia. The data suggest that EA-produced anti-hyperalgesia
      is mediated by PTX-sensitive Gi/o proteins and the relevant signaling pathways.

PMID- 15862794
TI  - Craniofacial inputs to upper cervical dorsal horn: implications for somatosensory
      information processing.
AB  - The aim of this study was to characterize the properties of somatosensory neurons
      in the first 2 cervical spinal dorsal horns (C1 and C2 DHs) and compare them with
      those previously described for the rostral subnucleus caudalis (rVc). A total of
      74 nociceptive neurons classified as wide-dynamic-range (WDR) or nociceptive
      specific (NS), as well as 72 low-threshold mechanoreceptive (LTM) neurons, was
      studied in urethane/chloralose-anesthetized rats. The majority of LTM neurons
      were located in laminae III/IV and had a small mechanoreceptive field (RF) that
      included the posterior face and cervical tissues. In contrast, the nociceptive
      neurons were located in laminae I/II or V/VI, and the RF of each C1 and C2 DH
      nociceptive neuron included a part of the face and in 47% of them the RF included
      a region supplied by upper cervical afferents. There was a gradual caudal shift
      in the neuronal RF from nasal/intraoral tissues towards the neck as recording
      sites progressed from rVc to C1 and C2 DHs. In contrast to LTM neurons, many C1
      and C2 DH nociceptive neurons received mechanosensitive convergent afferent
      inputs from cervical and craniofacial deep tissues (e.g., tongue muscles or
      temporomandibular joint), and over 50% could be activated by hypoglossal (XII)
      nerve electrical stimulation. We propose that C1 and C2 DHs represent part of the
      caudal extension of the Vc, and that Vc and C1 and C2 DHs may act together as one
      functional unit to process nociceptive information from craniofacial and cervical
      tissues, including that from deep craniofacial tissues.

PMID- 15862795
TI  - The role of CRF1 receptors for sympathetic nervous response to laparotomy in
      anesthetized rats.
AB  - Corticotropin-releasing factor (CRF) is released in response to various types of
      stressors and mediates endocrine, autonomic, immune, and behavioral responses to
      stress through interaction with CRF1 and CRF2 receptors. To investigate the role
      of CRF1 receptors in physiological responses to surgical stress, we analyzed the
      effects of two different non-peptide selective CRF1 receptor antagonists (JTC-017
      and CP-154,526) and a peptide non-selective CRF receptor antagonist (astressin)
      on laparotomy-induced sympathetic nervous responses in isoflurane-anesthetized
      rats. JTC-017, CP-154,526, and astressin similarly suppressed plasma ACTH
      elevation induced by laparotomy. JTC-017 and CP-154,526 significantly augmented
      plasma noradrenaline and adrenaline responses to laparotomy, while astressin
      showed no effect on these responses. Laparotomy-induced maximum increases in mean
      blood pressure and heart rate were augmented by JTC-017, but were not affected by
      astressin. The results suggested for the first time that there was a pathway to
      attenuate sympathetic nervous response to surgical stress through CRF1 receptors
      in the central nervous system.

PMID- 15862796
TI  - Orexin-A (hypocretin-1) is possibly involved in generation of anxiety-like
      behavior.
AB  - Orexins (hypocretins) are neuropeptides expressed specifically in neurons in the
      lateral hypothalamic area and are known to be involved in the regulation of
      vigilance and feeding behavior. However, the relationship between orexin and
      emotional behaviors like anxiety is still poorly understood. Therefore, in this
      report we evaluated the effect of intracerebroventricular injection of orexin-A
      in two major anxiety tests, the light-dark exploration test (mouse) and the
      elevated plus-maze test (mouse, rat). Orexin increased time spent in the dark
      compartment in the light-dark test and time spent on the closed arms in the
      elevated plus-maze test. These results were not caused by a hypothetical sedative
      or activity-inducing effect of orexin-A because spontaneous locomotor activity
      did not alter upon orexin-A application under novel conditions. We therefore
      suggest an anxiogenic effect of orexin-A. To our knowledge, this is the first
      report about a relationship between orexin-A and anxiety.

PMID- 15862797
TI  - Genesis of the decrement of intraluminal pressure in the UES during swallowing in
      rabbits.
AB  - The intraluminal pressure in the upper esophageal sphincter (UES) briefly
      decreases during swallowing. This decrement in pressure plays an important role
      in smooth transport of the ingested bolus from the pharynx to the esophagus. It
      is known that the decrement is caused by cessation of tonic activity of the
      cricopharyngeus (CP) muscle and also by elevation of the larynx. On the other
      hand, it is suspected that the recurrent laryngeal nerve (RLN) also contributes
      to the decrement, since our preliminary study showed for the first time that the
      decrement in UES pressure was much reduced after the RLN was sectioned. In the
      present study, we examined the genesis of the decrement of the UES pressure in
      anesthetized rabbits. When swallowing was elicited by repetitive electrical
      stimulation of the superior laryngeal nerve, the UES pressure briefly decreased
      and then abruptly increased. After bilateral sectioning of the RLN, the decrement
      of the pressure was significantly reduced, whereas the increment was little
      altered. Sectioning of the pharyngeal branch of the vagus nerve (X-ph) and the
      RLN mostly eliminated both the decrement and increment of the pressure, and
      abolished tonic and burst activities of the CP muscle. Electrical stimulation of
      peripheral end of the RLN decreased the pressure. These results indicate that the
      RLN and X-ph are involved in the decrement of the UES pressure during swallowing.
      The RLN generates the decrement by adducting the arytenoid cartilage and closing
      the glottis. The X-ph contributes to the decrement both by suppressing the tonic
      activity of the CP muscle and by regulating the laryngeal elevation.

PMID- 15862798
TI  - The inhibitory effects of peripheral administration of peptide YY(3-36) and
      glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal
      brainstem-hypothalamic pathway.
AB  - The vagus nerve forms a neuro-anatomical link between the gastrointestinal tract
      and the brain. A number of gastrointestinal hormones, including cholecystokinin
      and ghrelin, require an intact vagal-brainstem-hypothalamic pathway to affect CNS
      feeding circuits. We have shown that the effects of peripheral administration of
      both peptide YY(3-36) (PYY(3-36)) and glucagon-like peptide-1 (GLP-1) on food
      intake and activation of hypothalamic arcuate feeding neurones are abolished
      following either bilateral sub-diaphragmatic total truncal vagotomy or brainstem
      hypothalamic pathway transectioning in rodents. These findings suggest that the
      vagal-brainstem-hypothalamic pathway may also play a role in the effects of
      circulating PYY(3-36) and GLP-1 on food intake.

PMID- 15862799
TI  - Gentisic acid, an aspirin metabolite, inhibits oxidation of low-density
      lipoprotein and the formation of cholesterol ester hydroperoxides in human
      plasma.
AB  - Gentisic acid, an aspirin metabolite, has an antioxidant effect, although its
      detailed mechanism remains elusive. The present study was designed to determine
      whether it inhibits low-density lipoprotein (LDL) oxidation and the formation of
      lipid hydroperoxides in human plasma. The susceptibility of LDL oxidative
      modification was investigated by a method using 2,2'-azobis or Cu2+. To study the
      effect of gentisic acid on free radical-induced damage to plasma lipids,
      cholesterol ester hydroperoxides generated by incubating human fresh plasma with
      Cu2+ and gentisic acid was analyzed. Gentisic acid inhibited LDL oxidation in a
      concentration-dependent manner. It significantly inhibited the formation of
      cholesterol ester hydroperoxides in plasma, and was consumed after the depletion
      of ascorbic acid and reduced form of coenzyme Q-10 (CoQH2-10), whereas
      concentrations of other antioxidants remained unchanged. Gentisic acid had a
      potent free radical scavenging activity with a minimal chelating effect. The
      potent antioxidant property of gentisic acid may partly account for the anti
      atherogenic effects of aspirin.

PMID- 15862800
TI  - Molecular and pharmacological characterization of serotonin 5-HT2A and 5-HT2B
      receptor subtypes in dog.
AB  - We report the cloning, molecular characterization, and pharmacological
      characterization of the canine 5-HT2A and 5-HT2B receptors. The canine and human
      5-HT2A receptors share 93% amino acid homology. The canine and human 5-HT2B
      receptors are also highly conserved (87% homology) with the exception of the
      carboxyl termini where the canine protein is 62 amino acids shorter. Both the
      canine 5-HT2A and 5-HT2B receptors have high affinity for [3H]5-HT (KD=4.50+/
      0.89 nM and 3.10+/-0.82 nM, respectively) and, in general, the pharmacology of
      these two receptors matches closely the pharmacology of their human homologs for
      the 19 serotonergic ligands tested. However, the functional response (Ca2+
      mobilization) of the canine 5-HT2B receptor to several agonists was weaker
      compared to the human 5-HT2B receptor. Using quantitative reverse transcriptase
      polymerase chain reaction, a high expression level of canine 5-HT2A receptor mRNA
      was detected in the brain and lower levels in peripheral tissues, whereas the
      highest levels of canine 5-HT2B receptor mRNA were observed in lungs and smooth
      muscles. A significant level of canine 5-HT2B receptor mRNA was detected in brain
      tissue. The availability of the full sequence and pharmacology of the canine 5
      HT2A and canine 5-HT2B receptors provides useful information for the
      interpretation of previous and future pharmacological studies of 5-HT2A/2B
      ligands in dog.

PMID- 15862801
TI  - Putative role of nitric oxide synthase isoforms in the changes of nitric oxide
      concentration in rat brain cortex and cerebellum following sevoflurane and
      isoflurane anaesthesia.
AB  - We have previously observed an increase in nitric oxide (NO) content in rat brain
      cortex following halothane, sevoflurane or isoflurane anaesthesia. This study was
      undertaken in order to determine whether isoform-specific nitric oxide synthase
      (NOS) inhibitors and inducers could modify these increases in NO contents. Rats
      were subjected to isoflurane and sevoflurane anaesthesia with concomitant
      administration of neuronal nitric oxide synthase (nNOS) inhibitor 7-Nitro
      indazole (7-NI), inducible nitric oxide synthase (iNOS) inhibitor 2-amino-5,6
      dihydro-6-methyl-4H-1,3-thiazine (AMT) or lipopolysaccharide. NO concentration in
      different organs was measured by electron paramagnetic resonance (EPR)
      spectroscopy. 7-NI significantly decreased NO concentration in cerebellum but not
      in brain cortex, whereas AMT decreased NO in all the organs studied. Anaesthesia
      significantly increased NO concentration in brain cortex and decreased that in
      cerebellum. AMT abolished the NO increase in brain cortex. Anaesthesia enhanced
      the drastic increase in NO concentration in brain cortex after intraventricular
      lipopolysaccharide administration. Isoflurane was found to inhibit recombinant
      nNOS and iNOS activities at high concentrations (EC50=20 mM). Our data suggest a
      putative role for iNOS in the increase in NO levels produced by isoflurane and
      sevoflurane, whereas nNOS activity is probably inhibited during anaesthesia.

PMID- 15862802
TI  - Is antagonism of alpha3beta4 nicotinic receptors a strategy to reduce morphine
      dependence?
AB  - 18-Methoxycoronaridine, a synthetic iboga alkaloid congener, has been previously
      shown to attenuate several signs of morphine withdrawal in rats. The recently
      discovered action of 18-methoxycoronaridine to block alpha3beta4 nicotinic
      receptors may be responsible for this effect. To test this hypothesis the effects
      of non-selective alpha3beta4 receptor antagonists, dextromethorphan,
      mecamylamine, bupropion, and their combinations, were assessed on of acute
      naltrexone-precipitated (1 mg/kg i.p.) morphine withdrawal in rats.
      Dextromethorphan (5-40 mg/kg, s.c.), mecamylamine (0.25-4 mg/kg, i.p.) and
      bupropion (10-30 mg/kg, i.p.) alone produced variable effects on signs of
      withdrawal. However, two low-dose combinations, i.e., dextromethorphan (5 mg/kg,
      s.c.) and mecamylamine (0.25 mg/kg, i.p.), mecamylamine (0.25 mg/kg, i.p.) and
      bupropion (10 mg/kg, i.p.) as well as the three-drug combination significantly
      attenuated diarrhea and weight loss; none of the agents administered alone had
      these effects. The results of the present study provide evidence that alpha3beta4
      nicotinic receptors are involved in the expression of at least two signs of
      opioid withdrawal.

PMID- 15862803
TI  - Hydrogen peroxide and endothelium-dependent hyperpolarization in the guinea-pig
      carotid artery.
AB  - This study was designed to determine whether or not endothelium-dependent
      hyperpolarizations evoked by acetylcholine in the isolated guinea-pig carotid
      artery involve hydrogen peroxide. Membrane potential was recorded in the vascular
      smooth muscle cells of that artery. Under control conditions, acetylcholine
      induced endothelium-dependent hyperpolarization of the vascular smooth muscle
      cells which was not affected by the presence of catalase, superoxide dismutase or
      their combination. Neither the superoxide dismutase mimetic, tiron nor the thiol
      reducing agent N-acetyl-L-cysteine modified the hyperpolarization evoked by 0.1
      microM acetylcholine but each produced a partial and significant inhibition of
      the hyperpolarization induced by 1 microM acetylcholine. Neither 10 nor 100
      microM hydrogen peroxide influenced the resting membrane potential of the smooth
      muscle cells and the higher concentration did not significantly influence the
      hyperpolarization elicited by acetylcholine. These data indicate that, in the
      guinea-pig isolated carotid artery, hydrogen peroxide is unlikely to contribute
      to the endothelium-dependent hyperpolarization evoked by acetylcholine.

PMID- 15862804
TI  - Agonism at 5-HT2B receptors is not a class effect of the ergolines.
AB  - Restrictive cardiac valvulopathies observed in Parkinson patients treated with
      the ergoline dopamine agonist pergolide have recently been associated with the
      agonist efficacy of the drug at 5-hydroxytryptamine2B (5-HT2B) receptors. To
      evaluate whether agonism at 5-HT2B receptors is a phenomenon of the class of the
      ergolines, we studied 5-HT2B receptor-mediated relaxation in porcine pulmonary
      arteries to five ergolines which are used as antiparkinsonian drugs. Pergolide
      and cabergoline were potent full agonists in this tissue (pEC50 8.42 and 8.72).
      Bromocriptine acted as a partial agonist (pEC50 6.86). Lisuride and terguride,
      however, failed to relax the arteries but potently antagonized 5-HT-induced
      relaxation (pKB 10.32 and 8.49). Thus, agonism at 5-HT2B receptors seems not to
      be a class effect of the ergolines.

PMID- 15862805
TI  - Effect of celecoxib, a cyclooxygenase-2 inhibitor, on the pathophysiology of
      adjuvant arthritis in rat.
AB  - We investigated the efficacy of celecoxib, a specific cyclooxygenase (COX)-2
      inhibitor, on arthritic pathophysiology and confirmed its gastric safety in
      adjuvant-induced arthritis rats. Results were compared with those for loxoprofen,
      a non-selective COX inhibitor. Arthritis was induced by injection of 1 mg of
      Mycobacterium butyricum in 50 microl of liquid paraffin into the left footpad of
      Lewis rats. The drugs were given by twice daily oral administration for 10 days
      beginning 15 days after adjuvant injection, with celecoxib at 0.01-3 mg/kg/day
      and loxoprofen at 0.01-3 mg/kg/day. Celecoxib significantly inhibited paw
      swelling, hyperalgesic response, and joint destruction (radiographic and
      histopathological findings) in these arthritic rats. These effects of celecoxib
      were superior to those of loxoprofen. Further, the administration of loxoprofen
      (3 mg/kg/day) caused significant gastric lesions, whereas celecoxib at the same
      dose did not. These results suggest that COX-2-mediated prostaglandins may play
      an important role in the progression of pathophysiology in this model and that
      celecoxib may be a useful therapeutic agent for the treatment of rheumatoid
      arthritis, with greater safety than non-selective COX inhibitors.

PMID- 15862806
TI  - Suppression of lipopolysaccharide-induced expression of inducible nitric oxide
      synthase by brazilin in RAW 264.7 macrophage cells.
AB  - Brazilin (7,11b-dihydrobenz[b]indeno[1,2-d]pyran-3,6a,9,10 (6H)-tetrol) isolated
      from Caesalpinia sappan has been known as a natural red pigment. Many studies
      suggest that inducible isoform of nitric oxide synthase (NOS) plays an important
      role in inflammation and carcinogenesis. On this line, we evaluated the
      inhibitory effect of brazilin on nitric oxide (NO) production and investigated
      its mechanism of action. As a result, brazilin exhibited the inhibitory effect on
      lipopolysaccharide (LPS)-stimulated NO production in a dose-dependent manner
      (IC50=24.3 microM). In addition, brazilin suppressed LPS-induced iNOS protein and
      mRNA expression in RAW 264.7 macrophage cells, indicating that the inhibitory
      activity of brazilin possibly involved in the regulation of iNOS expression. To
      further investigate the mechanism responsible for the suppression of iNOS gene
      expression by brazilin, the effect of brazilin on LPS-induced transcription
      factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1)
      activation was examined. The DNA binding activity of NF-kappaB and AP-1
      stimulated LPS was inhibited by treatment of brazilin in a dose-dependent manner,
      suggesting that brazilin-mediated inhibition of NO production might be associated
      with the regulation of transcription factors NF-kappaB and AP-1. Taken together,
      these findings suggest that the suppressive effect of iNOS gene expression by
      brazilin might provide one possible mechanism for its anti-inflammatory and
      cancer chemopreventive activity.

PMID- 15862807
TI  - Effects of oleoyl-estrone with dexfenfluramine, sibutramine or phentermine on
      overweight rats.
AB  - We studied the combination of oleoyl-estrone with either dexfenfluramine,
      sibutramine or phentermine in overweight male rats treated for 10 days in order
      to determine whether they shared a mechanism of action. Oleoyl-estrone,
      dexfenfluramine and sibutramine decreased body weight and energy (essentially
      lipids); losses were higher when combined with oleoyl-estrone. Glycemia was
      maintained except under phentermine; oleoyl-estrone induced decreases in
      triacylglycerols, cholesterol, insulin and HOMA (homeostasis model assessment).
      Combination of oleoyl-estrone and sibutramine resulted in the loss of up to 29%
      body energy in 10 days. Energy expenditure was maintained. The effects of oleoyl
      estrone and dexfenfluramine or sibutramine on appetite were substantially
      additive. All oleoyl-estrone-treated rats showed increased insulin sensitivity.
      In conclusion, combined treatment of overweight rats with oleoyl-estrone and
      sibutramine or dexfenfluramine results in a dramatic loss of weight and fat,
      whilst maintaining circulating energy homoeostasis.

PMID- 15862808
TI  - Social, economic, and environmental influences on disorders of hearing, language,
      and speech.

PMID- 15862809
TI  - Public health research at the CDC: implications for communication sciences and
      disorders.
AB  - The following paper provides an overview of public health research at the Centers
      for Disease Control and Prevention (CDC), with emphasis on research involving
      speech, language and hearing disorders. Public health research involves a
      sequence of activities from disease tracking to disease prevention. Public health
      focuses on populations and works to identify changes in programs and policies
      that can positively impact population health. This paper uses three recent
      studies conducted by CDC investigators to illustrate different types of research
      along the public health prevention continuum, with emphasis on activities
      involving speech, language, and hearing endpoints. The three examples are: a
      study of cochlear implants and the subsequent risk of meningitis (illustrative of
      a public health response); a study examining the prevalence of autism in several
      U.S. populations (an example of a surveillance or monitoring activity); and a
      study examining the role of in utero cigarette exposure in the etiology of oral
      facial clefts (illustrative of a epidemiologic risk factor study). The public
      health continuum provides an important vehicle for advancing our knowledge of the
      causes and effective prevention of communication disorders. LEARNING OUTCOMES:
      The reader will become familiar with the public health sequence and the manners
      in which public health research relates to speech, language, and hearing
      disorders. The reader will be able to identify and discriminate among the
      components of public health research using the examples provided.

PMID- 15862810
TI  - Socioeconomic status and cultural influences on language.
AB  - Two studies track connections from the distal variables of socioeconomic status
      (SES) and culture to properties of the interactions children experience and to
      the rate of children's language development. The first study is an investigation
      of the relations among family SES, properties of maternal child-directed speech,
      and child vocabulary growth in a sample of 2-year-olds in the United States. The
      second study is an investigation of the relations among maternal education,
      maternal "language teaching practices," and child vocabulary and grammatical
      development in a sample of 2-4-year-olds in China. Together these findings reveal
      some of the ways in which the social and cultural contexts in which children live
      affect the course of their language development. LEARNING OUTCOMES: The reader
      will become aware of how the social and cultural milieu in which children live
      shapes their language experiences and consequent language development.

PMID- 15862811
TI  - Prenatal alcohol and cocaine exposure: influences on cognition, speech, language,
      and hearing.
AB  - This paper reviews research on the consequences of prenatal exposure to alcohol
      and cocaine on children's speech, language, hearing, and cognitive development.
      The review shows that cognitive impairment, learning disabilities, and behavioral
      disorders are the central nervous system manifestations of fetal alcohol syndrome
      (FAS), and cranio-facial abnormalities are also present. Delays in language
      acquisition, as well as receptive and expressive language deficits, are commonly
      reported. The cranio-facial abnormalities of FAS, which sometimes include cleft
      palate, make the child prone to otitis media with effusion and conductive hearing
      loss. The family environment in which one or both parents is a heavy alcohol user
      presents challenges to a child with normal intelligence, but may be especially
      deleterious to the child with mental retardation. Prenatal exposure to cocaine
      results in subtle cognitive disabilities when measured at 4 years of age. The
      cognitive effects may be ameliorated by a stimulating and sensitive care-giving
      environment. A small, deleterious "cocaine-effect" is also seen in speech and
      language development. The child with prenatal exposure to cocaine may be
      considered at increased risk for language delay or disorder. There is no evidence
      that prenatal cocaine exposure by itself is a risk factor for sensorineural
      hearing impairment, although auditory evoked potentials from the brainstem and
      cortex suggest some abnormalities in central auditory processing, at least during
      the newborn period. The strong effect of the home environment for ameliorating
      the effects of prenatal cocaine-exposure suggests that a family-focused approach
      for cognitive, language, and social-emotional habilitation would be beneficial to
      all. LEARNING OUTCOMES: The learner will be able to describe the major features
      of fetal alcohol syndrome and how they relate to speech, language, hearing, and
      cognitive disorders. The learner will review the literature and determine
      research needs with respect to language, speech, and hearing among infants and
      children with fetal alcohol syndrome. Similarly, the learner will distinguish the
      outcomes of prenatal alcohol-exposure from those of prenatal cocaine-exposure.
      The learner will summarize the controversy regarding the possible stigmatization
      of cocaine-exposed infants. The learner will summarize the speech, language, and
      hearing effects of prenatal cocaine-exposure.

PMID- 15862812
TI  - HIV and communication.
AB  - The human immunodeficiency virus (HIV) continues to plague many countries across
      the globe, including the United States, Africa, China and India. Children and
      adults have been infected with HIV, and both populations can present with
      communication disorders that coexist with the presence of the virus. The purpose
      of this paper is to present an overview of HIV and a discussion of the types of
      conditions that impact communication in both pediatric and adult populations.
      Persons living with HIV may present with disorders in the areas of language,
      phonology, voice and swallowing. Given the advances in pharmacological management
      of HIV, speech-language pathologists need to be knowledgeable of how medications
      can impact communication and swallowing. Also, since HIV crosses the blood-brain
      barrier and impacts all aspects of an infected person's life, speech-language and
      hearing professionals need to be members of the interdisciplinary teams that
      assess and manage patients living with HIV. Specific information regarding
      communication disorders in the pediatric population and research issues that
      warrant continued investigation will be addressed. LEARNING OUTCOMES: The reader
      will become aware of the ways in which a speech-language pathologist or
      audiologist may become involved with a patient infected with HIV or AIDS. The
      reader will learn the specific manners in which HIV and AIDS may affect the
      speech, language, hearing, and swallowing of pediatric and adult patients, as
      well as the appropriate intervention philosophies.

PMID- 15862813
TI  - Language-learning disorders and youth incarceration.
AB  - Many speech-language pathologists are serving delinquent boys with language
      learning disorders who are both current and former residents of correctional
      institutions. These youngsters demonstrate personal maladjustments that have a
      negative impact on school performance and socialization. Those boys within
      chaotic families are at risk of poverty, institutionalization, and substance
      abuse. Boys with language-learning disorders, who have encountered the law, need
      to be provided with services through collaborative and individualized efforts
      toward improving language skills, learning, and re-incorporating them into
      society. Further investigations are needed in order to clarify how the elements
      of personal, family, neighborhood, school and service conditions serve as either
      protective or risk factors for a life of incarceration in these individuals.
      LEARNING OUTCOMES: As a result of this presentation, the reader will understand
      the complex relationship among language-learning disorders, poverty, poor school
      performance, and delinquency in boys. The reader will become aware of the
      elements that should be present in school and correctional services in order to
      prevent recidivism in boys with language-learning disorders who have had problems
      with the law.

PMID- 15862814
TI  - Hearing loss and auditory function in sickle cell disease.
AB  - Sickle cell disease was first reported in 1910 by J. Herrick, and since then,
      various associated conditions and complications have been described. Sickle cell
      disease is a hereditary disorder characterized by abnormality of the hemoglobin
      in the red blood cell. During periods of decreased oxygen tension in the red
      blood cell's environment, the abnormal hemoglobin within the red blood cell
      polymerizes and causes it to assume its sickled shaped. This morphological change
      and its associated physiological changes drastically reduce the ability of red
      blood cells to navigate and deliver oxygen throughout the body. Sickle cell
      disease is a significant health problem affecting 1 in 400 African-Americans in
      the United States. One in 10 African-Americans in the United States has sickle
      cell trait. A variety of hemoglobinapathies are classified as sickle cell
      disease. Variants that simultaneously occur with hemoglobin S in high frequency
      are hemoglobins C and beta Thalassemia, and less frequently hemoglobin E. Sickle
      cell disease is characterized by chronic hemolytic anemia, end-organ damage, a
      heightened susceptibility to infections, and intermittent episodes of vascular
      occlusion causing both acute and chronic pain. Neurological symptoms are frequent
      in patients diagnosed with sickle cell disease. Considering the vaso-occlusive
      nature of sickle cell disease, the potential for auditory damage is not
      unexpected. However, the incidence of subjective hearing impairment among sickle
      cell anemia subjects is very low; therefore, the interest in hearing loss
      associated with the disease is not in its symptomatology, but in its
      pathogenesis. The relationship between sickle cell anemia and hearing loss is
      documented, but little is known about the relationship. Numerous investigations
      have assessed peripheral auditory sensitivity with a wide disparity of results.
      In the article, we will discuss: In view of the diversity of results and
      speculative etiology presented here and in the literature, the relationship
      between sickle cell anemia, auditory sensitivity, and auditory function warrants
      additional investigation. LEARNING OUTCOMES: As a result of this activity, the
      participant will read descriptions of the genetic and pathophysiological
      characteristics of sickle cell disease. The participant will examine evidence of
      the prevalence of hearing loss and auditory dysfunction in the sickle cell
      population, as well as the overall hearing health risk for sickle cell patients
      in comparison to the risk for the normal hemoglobin population. The participant
      will examine a model for appropriate audiological assessment of treatment of
      patients with sickle cell disease.

PMID- 15862815
TI  - Overview of the FASEB 2004 summer research conference on steroid hormone
      receptors: integration of plasma membrane and nuclear-initiated signaling in
      hormone action.

PMID- 15862816
TI  - Nongenomic effects of mineralocorticoid receptor activation in the cardiovascular
      system.
AB  - Fifteen years ago Wehling and colleagues showed unequivocal rapid effects of
      aldosterone, neither mimicked by cortisol nor blocked by spironolactone, and
      postulated that these nongenomic effects are mediated via a membrane receptor
      distinct from the classical mineralocorticoid receptor (MR). Several recent
      studies have challenged this view. Alzamora et al. showed 11beta-hydroxysteroid
      denydrogenase 1 and 2 (11betaHSD1, 11betaHSD2) expression in human vascular
      smooth muscle cells, and that aldosterone rapidly raises intracellular pH via
      sodium-hydrogen exchange; cortisol is without effect and spironolactone does not
      block the aldosterone response. When, however, 11betaHSD activity is blocked by
      carbenoxolone, cortisol shows agonist effects indistinguishable from aldosterone;
      in addition, the effect of both aldosterone and cortisol is blocked by the open E
      ring, water soluble MR antagonist RU28318. In rabbit cardiomyocytes, aldosterone
      increases intracellular [Na+] by activating Na+/K+/2Cl- cotransport, with
      secondary effects on Na+/K+ pump activity. Pump current rises approximately 10
      fold within 15', is unaffected by actinomycin D or the MR antagonist canrenone,
      and not elevated by cortisol. Pump current is, however, completely blocked by the
      open E-ring, water soluble MR antagonist K+ canrenoate and stoichometrically by
      cortisol. PKCepsilon agonist peptides (but not PKCalpha, PKCdelta or scrambled
      PKCepsilon peptides) mimic the effect of aldosterone, and PKCepsilon antagonist
      peptides block the effect. Very recently, cortisol has been shown to mimic the
      effect of aldosterone when cardiomyocyte redox state is altered by the
      installation of oxidized glutathione (GSSG) via the pipet, paralleling the effect
      of carbenoxolone on vascular smooth cells and suggesting possible
      pathophysiologic roles for an always glucocorticoid occupied MR.

PMID- 15862817
TI  - Specific modulation of nongenomic androgen signaling in the ovary.
AB  - Maturation, or meiotic progression, of amphibian oocytes is one of the few
      physiologically relevant steroid-mediated processes that occurs in the complete
      absence of transcription from beginning to end. As such, frog oocyte maturation
      has served as a useful model of nongenomic steroid signaling for many years.
      Earlier work in Xenopus laevis demonstrated that, although several steroids
      promoted oocyte maturation in vitro, androgens were the most abundant and potent
      steroids detected in the serum and ovaries of ovulating frogs. Thus, androgens
      were likely the primary physiologic regulators of Xenopus oocyte maturation,
      mediating their actions at least in part via classical androgen receptors
      expressed in oocytes. The importance of androgens for Xenopus oocyte maturation
      and ovulation has now been confirmed, as inhibition of androgen production in
      vivo by blocking CYP17 activity reduced hCG-triggered oocyte maturation and
      delayed ovulation in female frogs. Taking advantage of the absolute transcription
      independence of this androgen-mediated response, selective androgen receptor
      modulators (SARMs) have been characterized that specifically promote genomic
      versus nongenomic androgen responses. These include androstenediol and estren,
      which preferentially promote nongenomic signals, as well as R1881 and 19
      nortestosterone, which preferentially promote genomic signaling. Interestingly,
      the SARMs androstenediol and R1881 signal similarly in mouse oocytes,
      demonstrating the conserved nature of androgen-mediated maturation in
      vertebrates. These results suggest that SARMs may serve as useful tools for
      specifically regulating nongenomic androgen signaling both in vitro and in vivo.

PMID- 15862818
TI  - Requirements for estrogen receptor alpha membrane localization and function.
AB  - The estrogen receptor alpha (ERalpha) exists as a functional receptor at the
      plasma membrane. The structural requirements for localization and function are
      not well understood. Several laboratories have recently elucidated certain
      requirements. We recently found the translocation of ERalpha to the membrane in
      the absence of estrogen is dependent on caveolin-1 and serine 522 of the ERalpha
      protein. Mutation of serine 522 to alanine results in a 62% decrease in membrane
      localization and association with caveolin-1. Similarly, deletion of the caveolin
      1 scaffolding domain (amino acids 60-100) largely prevents the localization of
      ERalpha at the plasma membrane. In the presence of estradiol (E2), ERalpha, Src
      homology and collagen homology (Shc), and insulin-like growth factor receptor-1
      proteins associate with and increase the localization of ERalpha at the membrane.
      Membrane-localized ERalpha functions as an atypical G-protein coupled receptor.
      There is no good evidence that ERalpha spans the membrane or contains an
      extracellular domain. E2/ERalpha activates different G-proteins in cell context
      related fashion. These G-proteins lead to the activation of Src through PLC, PKC,
      IP3 and calcium influx. In breast cancer, Src activates matrix metalloproteinase
      2 and -9, which cleaves heparin binding epidermal growth factor, and thus
      activates EGFR. This leads to downstream signaling through ERK and PI3 kinase,
      imparting cell growth and survival.

PMID- 15862819
TI  - Signaling from the membrane via membrane estrogen receptor-alpha: estrogens,
      xenoestrogens, and phytoestrogens.
AB  - Estrogen mimetics in the environment and in foods can have important consequences
      for endocrine functions. When previously examined for action via genomic steroid
      signaling mechanisms, most of these compounds were found to be very weak
      agonists. We have instead tested their actions via several membrane-initiated
      signaling mechanisms in GH3/B6 pituitary tumor cells extensively selected for
      high (responsive) or low (nonresponsive) expression of the membrane version of
      estrogen receptor-alpha (mERalpha). We found many estrogen mimetic compounds to
      be potently active in our quantitative extracellular-regulated kinase (ERK)
      activation assays, to increase cellular Ca++ levels, and to cause rapid prolactin
      release. However, these compounds may activate one or both mechanisms with
      different potencies. For instance, some compounds activate ERKs in both pM and nM
      concentration ranges, while others are only active at nM and higher
      concentrations. Compounds also show great differences in their temporal
      activation patterns. While estradiol causes a bimodal time-dependent ERK
      activation (peaking at both 3 and 30 min), most estrogen mimetics cause either an
      early phase activation, a late phase activation, or an early sustained
      activation. One xenoestrogen known to be a relatively potent activator of
      estrogen response element-mediated actions (bisphenol A) is inactive as an ERK
      activator, and only a modest inducer of Ca++ levels and prolactin release. Many
      different signaling machineries culminate in ERK activation, and xenoestrogens
      differentially affect various pathways. Clearly individual xenoestrogens must be
      individually investigated for their differing abilities to activate distinct
      membrane-initiated signal cascades that lead to a variety of cellular functions.

PMID- 15862820
TI  - Estrogen and growth factor receptor interactions in human breast and non-small
      cell lung cancer cells.
AB  - Extranuclear estrogen receptors may mediate rapid effects of estradiol that
      communicate with nuclear receptors and contribute to proliferation of human
      cancers bearing these signaling proteins. To assess these growth-promoting
      pathways, we undertook controlled homogenization and fractionation of NIH-H23 non
      small cell lung cancer cells. As many breast tumors, NIH-H23 cells express
      estrogen receptors (ER), with the bulk of specific estradiol binding in nuclear
      fractions. However, as in breast cells, a significant portion of specific, high
      affinity estradiol-17beta binding-sites are also enriched in plasma membranes of
      lung tumor cells. These estrogen binding-sites co-purify with plasma membrane
      marker enzymes and are not significantly contaminated by cytosol or nuclei. On
      further purification of membrane caveolae from lung tumor cells, proteins
      recognized by monoclonal antibodies to nuclear ER-alpha and to ER-beta were
      identified in close association with EGF receptor in caveolae. In parallel
      studies, ER-alpha and ER-beta are also detected in nuclear and extranuclear sites
      in archival human breast and lung tumor samples and are noted to occur in
      clusters at the cell membrane by using confocal microscopy to visualize
      fluorescent-labeled monoclonal antibodies to ER-alpha. Data on site-directed
      mutagenesis of cysteine-447 in ER-alpha suggest that association of ER forms with
      membrane sites may depend on acylation of cysteine by palmitate. Estrogen-induced
      growth of MCF-7 breast cancer and NIH-H23 lung cancer cells in vitro correlated
      closely with acute hormonal activation of mitogen-activated protein kinase
      signaling and was significantly reduced by treatment with Faslodex, a pure anti
      estrogen. Further, combination of Faslodex with selected growth factor receptor
      inhibitors elicited a more pronounced inhibiton of tumor cell growth. Thus,
      extranuclear forms of ER play a role in promoting downstream signaling for
      hormone-mediated proliferation and survival of breast, as well as lung, cancers
      and offer a new target for anti-tumor therapy.

PMID- 15862821
TI  - Vascular cell signaling by membrane estrogen receptors.
AB  - There is substantial interest in the effects of estrogen on the vascular wall,
      due to the marked gender difference in the incidence of clinically apparent
      coronary heart disease (CHD), when comparing premenopausal women with age-matched
      males. Recent randomized clinical trials unexpectedly failed to demonstrate a
      hormone replacement therapy (HRT) benefit for CHD secondary or primary prevention
      in postmenopausal women. There are several possible explanations for these
      findings, which have created a conundrum in light of the numerous potentially
      beneficial vascular effects of estrogen demonstrated at the cellular, molecular,
      and even animal model level. Clinical trials are ongoing, and the dissection of
      molecular pathways continues. Although estrogen receptors (ERs) are traditionally
      defined as ligand-activated transcriptional activators or repressors, a
      phenomenon certainly involved in some of estrogen's beneficial effects on
      vascular cells, we and others have recently demonstrated the presence of membrane
      associated ERs in endothelial cells (EC), and that engagement of this subset of
      receptors may also contribute to the favorable molecular profile of the
      endothelium. In this review, we describe evidence for membrane-localized ERs in
      EC. We discuss features of their membrane targeting, and how they may differ from
      classical ERs. We also describe the rapid assembly of a membrane-associated
      molecular complex, comprised of ER, c-Src and the regulatory unit of
      phosphatidylinositol 3-kinase (PI3K), p85, in response to estrogen. Finally, we
      describe how this complex triggers sequential enzyme activation, involving
      endothelial nitric oxide synthase (eNOS), and consequent enhanced basal release
      of NO, a key modulator of vascular tone and 'healthy' blood vessels.

PMID- 15862822
TI  - Integration of steroid hormone initiated membrane action to genomic function in
      the brain.
AB  - Estrogen is a ligand for the estrogen receptor (ER), which on binding 17beta
      estradiol, functions as a ligand-activated transcription factor and regulates the
      transcription of target genes. This is the slow genomic mode of action. However,
      rapid non-genomic actions of estrogen also exist at the cell membrane. Using a
      novel two-pulse paradigm in which the first pulse rapidly initiates non-genomic
      actions using a membrane-limited estrogen conjugate (E-BSA), while the second
      pulse promotes genomic transcription from a consensus estrogen response element
      (ERE), we have demonstrated that rapid actions of estrogen potentiate the slower
      transcriptional response from an ERE-reporter in neuroblastoma cells. Since rapid
      actions of estrogen activate kinases, we used selective inhibitors in the two
      pulse paradigm to determine the intracellular signaling cascades important in
      such potentiation. Inhibition of protein kinase A (PKA), PKC, mitogen activated
      protein kinase (MAPK) or phosphatidylinositol 3-OH kinase (PI-3K) in the first
      pulse decreases potentiation of transcription. Also, our data with both dominant
      negative and constitutive mutants of Galpha subunits show that Galpha(q)
      initiates the rapid signaling cascade at the membrane in SK-N-BE(2)C
      neuroblastoma cells. We discuss two models of multiple kinase activation at the
      membrane Pulses of estrogen induce lordosis behavior in female rats. Infusion of
      E-BSA into the ventromedial hypothalamus followed by 17beta-estradiol in the
      second pulse could induce lordosis behavior, demonstrating the applicability of
      this paradigm in vivo. A model where non-genomic actions of estrogen couple to
      genomic actions unites both aspects of hormone action.

PMID- 15862823
TI  - Estrogen modulation of hypothalamic neurons: activation of multiple signaling
      pathways and gene expression changes.
AB  - Hypothalamic target neurons of estrogen include neurosecretory neurons such as
      gonadotropin-releasing hormone (GnRH) and dopamine neurons, and local circuitry
      neurons such as proopiomelanocortin (POMC) and gamma-aminobutyric acid (GABA)
      neurons. These and other hypothalamic neurons are involved in regulating numerous
      homeostatic functions including reproduction, thermoregulation, stress responses,
      feeding and motivated behaviors. Using a combination of techniques to examine the
      molecular mechanisms leading to physiological changes induced by estrogen, we
      find that both rapid effects and transcriptional changes alter excitability of
      hypothalamic neurons. We have identified membrane-initiated, rapid signaling
      pathways through which 17beta-estradiol (E2) alters synaptic responses in these
      neurons using whole-cell patch recording in hypothalamic slices from
      ovariectomized female guinea pigs. E2 rapidly uncouples mu-opioid and GABA(B)
      receptors from G protein-gated inwardly rectifying K+ (GIRK) channels in POMC and
      dopamine neurons as manifested by a reduction in the potency of mu-opioid and
      GABA(B) receptor agonists to activate these channels. Inhibitors of phospholipase
      C, protein kinase C and protein kinase A block the actions of E2, indicative that
      the E2 receptor is G protein-coupled to activation of this cascade. Taking
      advantage of an animal model we developed to investigate estrogen's feedback
      actions on secretion of gonadotropin-releasing hormone (GnRH), we studied the
      transcriptional changes induced by estrogen using suppression subtractive
      hybridization (SSH) and microarray analysis. Many of the observed mRNA expression
      changes include transcripts encoding proteins critical for neurotransmitter
      release and receptor dynamics. Some of these include gec-1, PI3-kinase p55gamma,
      rab11a GTPase, synaptobrevin2, synaptogyrin, taxilin, Ca2+-dependent activator
      protein for secretion (CAPS) and a number of proteins containing pleckstrin
      homology domains-domains that are involved in plasma membrane targeting of their
      host protein. In situ hybridization and quantitative film autoradiography
      analysis on selected transcripts show differential distribution and expression in
      hypothalamic nuclei. Furthermore, single-cell PCR analysis reveals these genes to
      be expressed in neurons such as POMC (and GnRH). Whether these expression changes
      are mediated by the classical or membrane estrogen receptors has yet to be
      delineated. More detailed investigations of transcript spatial localization
      within neurons and their temporal expression, i.e., within minutes or hours, will
      provide more insight regarding how estrogen alters neuronal excitability and
      synaptic efficacy that ultimately lead to changes in complex behavior.

PMID- 15862824
TI  - The human glucocorticoid receptor: one gene, multiple proteins and diverse
      responses.
AB  - Glucocorticoids are a vital class of endogenous steroid hormones that regulate
      essential biological processes including growth, development, metabolism,
      behavior and apoptosis. Most, if not all, of these actions are thought to be
      mediated through the glucocorticoid receptor. The exact mechanisms of how one
      hormone, via one receptor, modulates such diverse biological functions are
      largely unknown. However, recent studies from our lab and others have suggested
      that a contribution for the diversity results from multiple isoforms of the
      glucocorticoid receptor that result from alternative RNA splicing and translation
      initiation of the glucocorticoid receptor mRNA. Additionally, each isoform is
      subject to several post-translational modifications, including phosphorylation,
      ubiquitination and sumoylation, which have been shown to modulate the receptor
      protein stability and/or function. Together these data provide potentially
      diverse mechanisms to establish cell type specific regulation of gene expression
      by a single transcription factor. Here, we summarize the recent advances and
      processes that generate these receptor isoforms and these post-translational
      modifications. We speculate that the composition and proportion of individual
      isoforms expressed in particular cellular contexts account for the diverse
      effects of glucocorticoid hormones.

PMID- 15862825
TI  - Integration of progesterone receptor mediated rapid signaling and nuclear actions
      in breast cancer cell models: role of mitogen-activated protein kinases and cell
      cycle regulators.
AB  - Progesterone receptor (PR) isoforms are dual functioning steroid hormone
      receptors, capable of activation of target gene transcription, and rapid
      stimulation of membrane-initiated intracellular signaling cascades. Herein we
      provided a retrospective of our recent work investigating the role of progestin
      activated intracellular signaling pathways on cell cycle progression in breast
      cancer cell models. We show that progestin-induced S-phase entry and upregulation
      of selected target genes, including cyclin D1, are MAPK-dependent events. Further
      experiments conducted with mutant PRs defective in either the transcriptional
      response (PR-S294A) or activation of c-Src-dependent intracellular signaling to
      MAPKs (PR-mPro) confirmed that the proliferative response of breast cancer cells
      to progestins is largely dependent on the ability of PR to rapidly activate Erk
      1/2 MAPKs. During progestin-stimulated cell cycle progression, elevated cdk2
      levels and activity target multiple phosphorylation sites on PR. Phosphorylation
      of Ser400 augments PR nuclear localization and mediates increased PR
      transcriptional activity in the absence of hormone, while the cdk inhibitor, p27,
      reversed these effects. Together, our data illustrate the versatility of PR as
      regulatory signaling molecules that also act as sensors for multiple kinase
      pathways, and suggest that progestins influence changes in breast cancer cell
      gene expression and proliferation via integration of PR functions as both ligand
      activated transcription factors and rapid initiators of intracellular signaling
      pathways.

PMID- 15862826
TI  - Binding characteristics, hormonal regulation and identity of the sperm membrane
      progestin receptor in Atlantic croaker.
AB  - Recently a novel cDNA was discovered in spotted seatrout ovaries encoding a
      protein with seven transmembrane domains that has the characteristics of the
      membrane progestin receptor (mPR) mediating maturation-inducing steroid (MIS)
      induction of oocyte maturation in this species. Preliminary results suggested the
      MIS also activates an mPR on the spermatozoa of spotted seatrout and a closely
      related species, Atlantic croaker, to stimulate sperm motility. We show here that
      plasma membranes of croaker sperm demonstrate high affinity (Kd approximately 20
      nM), limited capacity (Bmax 0.08 nM), specific and displaceable binding for
      progestins that is characteristic of mPRs. The MIS (17,20beta,21-trihydroxy-4
      pregnen-3-one, 20beta-S) displayed the greatest binding affinity for the sperm
      mPR among the steroids tested. Treatment of croaker testicular tissue in vitro
      with gonadotropin caused a several-fold increase in sperm mPR receptor
      concentrations that was partially blocked in the presence of cyanoketone, which
      suggests this action of gonadotropin is partially mediated by stimulation of
      steroidogenesis. Protein bands of the predicted sizes for the mPR and its dimer
      (40 and 80 kDa) were detected by Western blotting of croaker sperm membranes
      using a specific antibody to the novel seatrout mPR (mPRalpha).
      Immunocytochemistry of whole croaker spermatozoa with the mPRalpha antibody
      showed that staining was primarily localized on the midpiece, consistent with a
      role of the mPRalpha in mediating MIS stimulation of sperm motility. The results
      suggest that the mechanism of progestin action on fish sperm involving mPRs is
      basically similar to that in mammals and has been evolutionarily conserved
      amongst vertebrates.

PMID- 15862827
TI  - Short-term effects of thyroid hormone in prenatal development and cell
      differentiation.
AB  - Extranuclear or nongenomic effects of thyroid hormones do not require interaction
      with the nuclear receptor, but are probably mediated by specific membrane
      receptors. This review will focus on the extranuclear effects of thyroid hormones
      on plasma membrane transport systems in non mammalian cells: chick embryo
      hepatocytes at two different stages of development, 14 and 19 days. At variance
      with mammals, the chick embryo develops in a closed compartment, beyond the
      influence of maternal endocrine factors. Thyroid hormones inhibit the Na+/K+
      ATPase but stimulate the Na+/H+ exchanger and amino acid transport System A with
      different dose-responses: a bell-shaped curve in the case of the exchanger and a
      classic saturation curve in the case of System A. These effects are mimicked by
      the analog 3,5-diiodothyronine. Signal transduction is mediated by interplay
      among kinases, mainly protein kinase C and the MAPK pathway, initially primed by
      second messengers such as Ca2+, IP3, and DAG as in mammalian cells. Thyroid
      hormones and 3,5-diiodothyronine stimulate thymidine incorporation and DNA
      synthesis, associated with the increased levels and activity of cyclins and
      cyclin-dependent kinases involved in the G1/S transition, and also these effects
      have their starting point at the plasma membrane. Increasing evidence now
      demonstrates that thyroid hormones act as growth factors for chick embryo
      hepatocytes and their extranuclear effects are important for prenatal development
      and differentiation.

PMID- 15862828
TI  - Acetylation of nuclear hormone receptor superfamily members: thyroid hormone
      causes acetylation of its own receptor by a mitogen-activated protein kinase
      dependent mechanism.
AB  - Because the androgen and estrogen nuclear hormone receptors are subject to
      acetylation, we speculated that the nuclear thyroid hormone receptor-beta1
      (TRbeta1), another superfamily member, was also subject to this posttranslational
      modification. Treatment of 293T cells that contain TRbeta1(wt) with l-thyroxine
      (T4)(10(-7)M, total concentration) resulted in the accumulation of acetylated TR
      in nuclear fractions at 30-45 min and a decrease in signal by 60 min. A similar
      time course characterized recruitment by TR of p300, a coactivator protein with
      intrinsic transacetylase activity. Recruitment by the receptor of SRC-1, a TR
      coactivator that also acetylates nucleoproteins, was also demonstrated.
      Inhibition of the MAPK (ERK1/2) signal transduction cascade by PD 98059 blocked
      the acetylation of TR caused by T4. Tetraiodothyroacetic acid (tetrac) decreased
      T4-induced acetylation of TR. At 10(-7)M, 3,5,3'-triiodo-l-thyronine (T3) was
      comparably effective to T4 in causing acetylation of TR. We studied acetylation
      in TR that contained mutations in the DNA-binding domain (DBD) (residues 128-142)
      that are known to be relevant to recruitment of coactivators and to include the
      MAPK docking site. In response to T4 treatment, the K128A TR mutant transfected
      into CV-1 cells recruited p300, but not SRC-1, and was subject to acetylation.
      R132A complexed with SRC-1, but not p300; it was acetylated equally well in both
      the absence and presence of T4. S142E was acetylated in the absence and presence
      of T4 and bound SRC-1 under both conditions; this mutant was also capable of
      binding p300 in the presence of T4. There was no serine phosphorylation of TR in
      any of these mutants. We conclude that (1) TRbeta1, like AR and ER, is subject to
      acetylation; (2) the process of acetylation of TR requires thyroid hormone
      directed MAPK activity, but not serine phosphorylation of TR by MAPK, suggesting
      that the contribution of MAPK is upstream in the activation of the acetylase; (3)
      the amino acid residue 128-142 region of the DBD of TR is important to thyroid
      hormone-associated recruitment of p300 and SRC-1; (4) acetylation of TR DBD
      mutants that is directed by T4 appears to be associated with recruitment of p300.

PMID- 15862829
TI  - Isoform-dependent actions of thyroid hormone nuclear receptors: lessons from
      knockin mutant mice.
AB  - Thyroid hormone nuclear receptors (TRs) mediate the biological activities of the
      thyroid hormone (T3) in growth, development and differentiation and in the
      maintenance of metabolic homeostasis. They are derived from two separate genes to
      yield four major T3-binding isoforms: alpha1, beta1, beta2, and beta3. To
      understand whether TR isoforms mediate specific functions in vivo, PV mutation,
      identified from a patient with resistance to thyroid hormone (RTH), was targeted
      to the TRbeta (TRbetaPV mice) or TRalpha gene (TRalpha1PV mice). PV has a frame
      shift mutation in the last 14 carboxyl-terminal amino acids of TRbeta1 or
      TRalpha1, resulting in the loss of T3-binding and transcriptional activities.
      TRbetaPV mice faithfully reproduce human RTH with dysfunction of the pituitary
      thyroid axis, impairment in weight gain and accelerated bone development, hearing
      defects, abnormal regulation of serum cholesterol and increased physical activity
      reminiscent of attention deficit-hyperactivity disorder. In contrast, TRalpha1PV
      mice show no abnormalities in the pituitary-thyroid axis and other discernable
      RTH phenotypes. In addition, TRalpha1PV mice are dwarfs with high mortality,
      reduced fertility and survival, reduced glucose utilization in the brain and
      marked delay in bone development. These results clearly show that the molecular
      actions of TRalpha1PV are distinct from those of TRbetaPV in vivo. Further
      studies indicate that these contrasting phenotypes are mediated by distinct
      isoform-dependent abnormal regulation of T3-target genes in tissues. Thus, these
      two mutant mice provide a valuable tool for further dissecting the molecular
      bases of isoform-dependent actions of mutant TRs in vivo and their roles in
      disease.

PMID- 15862830
TI  - The 1,25D3-MARRS protein: contribution to steroid stimulated calcium uptake in
      chicks and rats.
AB  - There are currently two main candidates for the membrane receptor for
      1,25(OH)2D3: the 1,25D3-MARRS protein/ERp57; and the classical VDR. The 1,25D3
      MARRS protein is essential for hormone-stimulated phosphate and calcium uptake in
      chick intestinal cells, whereas the VDR is not. The 1,25D3-MARRS protein also
      shows a high degree of correlation with growth periods in which bone is rapidly
      formed, whereas the VDR does not. However, in rat enterocytes, both the 1,25D3
      MARRS protein and the VDR play a role in the rapid, steroid-mediated uptake of
      phosphate or calcium. Therefore, the theory that alternate binding sites on the
      VDR for various analogs account for all membrane-initiated phenomena, is
      incorrect.

PMID- 15862831
TI  - Identification and characterization of 1,25D3-membrane-associated rapid response,
      steroid (1,25D3-MARRS)-binding protein in rat IEC-6 cells.
AB  - We report the presence of a mammalian equivalent of the avian Membrane-Associated
      Rapid Response, Steroid (1,25D3-MARRS)-binding protein specific for 1,25(OH)2D3
      in a rat small intestinal cell line, IEC-6, that demonstrates rapid responses to
      the steroid hormone. Identification of transcript and protein was achieved using
      RT-PCR with several specific primer sets, Western blot analysis with two separate
      antibodies recognizing distinct regions of the protein, ribozyme knockdown and
      immunohistochemistry. Promoter analysis of the 1000-bp upstream region of the
      1,25D3-MARRS gene in several species revealed the presence of a conserved smad-3
      element in the 5' proximal promoter region, but no classical vitamin D response
      element (VDRE). Treatment of IEC-6 cells with transforming growth factor beta1
      (TGFbeta1) increased steady-state levels of 1,25D3-MARRS (mRNA and protein)
      approximately two-fold over a 24-h period. In contrast, treatment with
      1,25(OH)2D3 failed to significantly change 1,25D3-MARRS protein or mRNA levels.
      Localization studies showed rapid nuclear translocation of a pool of 1,25D3-MARRS
      protein after 1,25(OH)2D3 treatment, suggesting that the protein is subject to
      membrane-initiated signal pathway activation. Together these data point to
      complex interactions between the two important 1,25(OH)2D3 sensitive response
      systems in intestinal cells, 1,25D3-MARRS protein and the well-studied nVDR, that
      together work to fine tune intestinal Ca2+ absorption in a variety of avian and
      mammalian species.

PMID- 15862832
TI  - Applications of the Vitamin D sterol-Vitamin D receptor (VDR) conformational
      ensemble model.
AB  - Over the past 20 years much has been learned about the cellular actions of the
      steroid hormone 1alpha,25(OH)2-Vitamin D3 (1,25D). Perhaps most importantly
      structure-function studies led to the discovery that different chemical and
      physical features of 1,25D are preferred to initiate either exonuclear, non
      genomic or endonuclear, genomic cellular signaling. It is well documented that
      both a 1alpha-OH and 25-OH, and a 6-s-trans, bowl-shaped, sterol conformation are
      absolutely required for efficient gene transcription, while 6-s-cis locked
      analogs and 1-deoxy, 25(OH)D3 metabolites activate a variety of non-genomic,
      rapid responses. These results and the observation that S237 (helix-3; H3) and
      R274 (H5) are the most static residues in the human 1,25D-Vitamin D receptor
      (VDR) X-ray construct (see B-values in pdb: 1DB1) and form H-bonds with the
      1alpha-OH of 1,25D in the X-ray, genomic pocket (G-pocket), provided the basis
      for the molecular modeling experiments that led to the discovery of a putative
      VDR alternative ligand binding pocket (A-pocket). The conformational ensemble
      model generated from the in silico results provides an explanation for how the
      VDR can function as a receptor propagating both genomic and non-genomic signaling
      events. In this report the theoretical gating properties controlling ligand
      access to the A- and G-pockets will be compared and the model will be used to
      provide a molecular explanation for the confusing structure-function results
      pertaining to 1,25D, its side-chain metabolite, 23S,25R-1alpha,25(OH)2-D3-26,23
      lactone (BS), and its synthetic two side-chain analog, 21-(3'-hydroxy-3'
      methylbutyl)-1alpha,25(OH)2-D3 (KH or Gemini). In addition, evidence that the
      model is consistent with the pH requirement for Vitamin D sterol-VDR
      crystallization will be presented.

PMID- 15862833
TI  - Review of evidence: are endocrine-disrupting chemicals in the aquatic environment
      impacting fish populations?
AB  - In this paper, evidence from the current literature is presented that addresses
      either of two questions: 1) do EDCs in the aquatic environment have the potential
      to impact the reproductive health and survival of various fish species, and 2)
      are EDCs in the aquatic environment actually impacting the reproductive health
      and sustainability of indigenous populations of fish? Overall, data from
      laboratory experiments support the hypothesis that EDCs in the aquatic
      environment can impact the reproductive health of various fish species, but
      evidence that EDCs in the aquatic environment are actually impacting the
      reproductive health and sustainability of indigenous fish populations is less
      convincing. The scarcity of evidence linking impacts of environmental EDCs with
      changes in reproductive success of indigenous fish populations may reflect a
      critical need for a dependable method or indicator to assess reproduction of fish
      in situ. In addition, more studies that investigate whether fish populations
      routinely exposed to EDCs in situ are experiencing changes in population
      structure are needed. Linking endocrine disruption and reproductive impairment
      with an ecologically relevant impact on the sustainability of real fish
      populations remains, with few exceptions, an open challenge.

PMID- 15862834
TI  - Whole-catchment application of dolomite to mitigate episodic acidification of
      streams induced by sea-salt deposition.
AB  - To counteract mobilisation of potentially toxic aluminium (Al) ions to
      tributaries of salmon rivers, two paired-catchment experiments with terrestrial
      liming at two sites on the Norwegian west coast were performed. Streams at both
      sites experienced episodically elevated and potentially toxic Al levels induced
      by high deposition of sea salts. After application of 2 metric tons ha-1 of 0.2-2
      mm dolomite powder at the Brommeland area, stream pH increased above critical
      levels at about pH=6.0 and remained stable throughout the monitoring period of
      3.5 years. Inorganic aluminium decreased to below 20 microg Al L-1, a water
      quality supposed to be nontoxic for salmon. This was evident also during extreme
      weather conditions with large relative increases in chloride (Cl) concentrations
      and negative calculated nonmarine sodium (Na*) concentrations in the streams,
      indicating potentially toxic sea-salt effects. Cl changed from being closely
      related to increases in inorganic Al, especially at the Brommeland stream
      (R2=0.75), to being not important (R2=0.12), but still significant for its
      variation. At the Hovland area, receiving 1 ton ha-1 of 0-2 mm dolomite powder,
      stream pH and Al effects were less clear-cut, probably due to the lower dolomite
      dose. Stream concentrations of both NO3- and SO4(2-) increased significantly due
      to liming.

PMID- 15862835
TI  - Influence of soil moisture on sunflower oil extraction of polycyclic aromatic
      hydrocarbons from a manufactured gas plant soil.
AB  - The influence of soil moisture on efficiency of sunflower oil extraction of
      polycyclic aromatic hydrocarbons (PAHs) from contaminated soil was investigated.
      The PAH-contaminated soil was collected from a manufactured gas plant (MGP) site
      in Berlin, Germany. Half of the soil was air-dried, and the other half was kept
      as field-moist soil. Batch experiments were performed using air-dried and field
      moist soils, and sunflower oil was used as extractant at oil/soil ratios of 2:1
      and 1:1 (v/m). The experimental data were fitted to a first-order empirical model
      to describe mass-transfer profiles of the PAHs. Column extraction experiments
      were also conducted. Field-moist and air-dried soils in the column were extracted
      using sunflower oil at an oil/soil ratio of 2:1. In the batch experiments, PAHs
      were more rapidly extracted from air-dried soil than from field-moist soil.
      Removal rate of total PAH increased 23% at oil/soil ratio of 1:1 and 15.5% at
      oil/soil ratio of 2:1 after the soil was air dried. The most favorable conditions
      for batch extraction were air-dried soil, with an oil/soil ratio of 2:1. In the
      column experiments, the removal rate of total PAH from air-dried soil was 30.7%
      higher than that from field-moist soil. For field-moist soil, extraction
      efficiencies of the batch extraction (67.2% and 81.5%) were better than that for
      column extraction (65.6%). However, this difference between the two methods
      became less significant for the air-dried soil, with a total removal rate of
      96.3% for column extraction and 90.2% and 97% for batch extractions. A mass
      balance test was carried out for analytical quality assurance. The results of
      both batch and column experiments indicated that drying the soil increased
      efficiency of extraction of PAHs from the MGP soil.

PMID- 15862836
TI  - Consumption of homegrown products does not increase dietary intake of arsenic,
      cadmium, lead, and mercury by young children living in an industrialized area of
      Germany.
AB  - The dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) was
      studied among young German children with different food consumption behaviour
      (consumption of own grown foodstuffs and of products from the supermarket). The
      study area comprised an industrialized and a rural area of West Germany. Dietary
      intake of contaminants was measured by the duplicate method according to the WHO
      guideline. A total 588 duplicate portions were collected daily from 84
      individuals between May and September 1998. Intake of food groups was calculated
      from dietary records. Determination of As, Cd, Hg, and Pb was performed following
      high-pressure digestion of lyophilized samples by atomic absorption spectrometry
      (AAS). Geometric mean weekly intake [microg/(kgbw x week)] was as follows: As
      1.4, Cd 2.3, Hg 0.16, and Pb 5.3. Geometric mean intake corresponded to the
      percentage of the provisional tolerable weekly intake (PTWI) as follows: As 9.7%,
      Cd 32%, Hg 3.3%, Pb 21%. As and Hg intake were mainly influenced by fish
      consumption. The amount of cereals and bakery wares mainly determined the Cd and
      Pb intake. Children living in the industrialized area with a substantial food
      consumption of own grown vegetables or products from domestic animals products
      had no increased dietary intake of the metals.

PMID- 15862837
TI  - The environmental impact of mastitis: a case study of dairy herds.
AB  - Mastitis is defined as an inflammatory reaction of udder tissue to bacterial,
      chemical, thermal or mechanical injury, which causes heavy financial losses and
      milk wastage throughout the world. Until now, studies have focused on the
      economic aspects from which perspective mastitis can generally be considered as
      the most serious disease in dairy cows; however, costs are not the only negative
      consequence resulting from the infection. The environmental impact is also
      significant; milk is discarded, which means lower efficiency and hence a greater
      environmental impact per produced liter of milk. Less milk is produced, which
      leads to an increased need for calf feed, and meat production is also affected.
      The main aim of this paper was to quantify the environmental impact of mastitis
      incidence. A standard scenario (representative of present-day reality in Galicia,
      Spain) and an improved scenario (in which mastitis incidence rate is reduced by
      diverse actions) have been defined and compared using Life Cycle Assessment (LCA)
      methodology. Among the impact categories studied, acidification, eutrophication
      and global warming were found to be the most significant environmental impacts.
      In all these categories, it was revealed that a decrease in mastitis incidence
      has a positive influence as the environmental impact is reduced. Even if the
      quantitative results cannot show a considerable decrease in the environmental
      burden, the impact cannot be regarded as negligible when the total consumption or
      total production of a region is considered. For example, the outcome of the
      proposed improvement measures for Spain's greenhouse gas emissions can be
      quantified as 0.06% of total emissions and 0.56% of emissions by the agricultural
      sector.

PMID- 15862838
TI  - Persistent organic pollutants in edible marine species from the Gulf of Naples,
      Southern Italy.
AB  - Edible tissues from 10 marine species, collected from the Gulf of Naples in the
      Southern Tyrrhenian Sea (Italy) between February and July 2003, were analysed for
      the presence of organochlorine pesticides hexachlorobenzene (HCB) and DDTs (p,p'
      DDT, p,p'-DDE, and p,p'-DDD), and 20 polychlorinated biphenyls (PCBs). The PCB
      levels (calculated as the sum of all the determined congeners) were found to be
      the highest (from 56.8 to 47909.5 ng/g on lipid basis), followed by the DDTs (sum
      of p,p'-DDT and its metabolites; <dl-2095.5 ng/g) and HCB (<dl-165.4 ng/g). There
      were marked differences in residue levels of DDTs and PCBs among the various
      species under investigation (from P<0.05 to P<0.001). Since the presence of
      organochlorine pollutants was most evident in the strictly resident species which
      inhabit shallow coastal waters, contamination of the Gulf of Naples by these
      compounds probably derives from local agricultural, industrial, and municipal
      sources. Concentrations of DDTs and PCBs detected in this study were generally
      comparable or higher than those found in studies of similar species from other
      Mediterranean and non-Mediterranean regions subject to a high anthropogenic
      impact. From the human health point of view, the residue levels of HCB and DDTs
      detected in this study are well below the Maximum Residue Limits for some foods
      of animal origin (0.2 and 1 mg/kg fat weight for HCB and DDTs calculated as the
      sum of p,p'-DDT, p,p'-DDE, p,p'-DDD, and o,p'-DDT, respectively). However, the
      concentrations of PCBs (calculated as the sum of the seven "target" congeners
      IUPAC nos. 28, 52, 101, 118, 138, 153, and 180) detected in all the analysed
      samples far exceed the action limit of 200 ng/g fat weight recommended by the
      European Union for eggs, fresh pig meat, fresh poultry meat, and derived
      products.

PMID- 15862839
TI  - Agronomic and environmental impacts of a single application of heat-dried sludge
      on an Alfisol.
AB  - A field experiment was conducted on Alfisols in South-West France to assess the
      agronomic and environmental impacts of a single application of heat-dried sludge
      pellets at 11.1 Mg dry matter ha-1. The sludge pellets, with a moisture level of
      9.5%, were spread on an irrigated crop of maize (Zea mays L.). This treatment was
      compared with inorganic fertilization (urea and diammonium phosphate mixed with
      KCl). Soil properties, yield and the composition of maize and the quality of
      drained water were monitored over 1 year to detect any changes resulting from
      sludge application. Amongst several determined soil properties, only two were
      significantly modified by the sludge application: The nitric nitrogen stock of
      the soil was higher in the inorganic fertilized plot, whereas Olsen-P soil
      content was higher in the sludge-amended plot. Agronomic recovery rates of N and
      P added by sludge were high: For the first crop following application, total
      amounts of N and P supplied by the sludge had the same efficiency as
      approximately 45% of the N and P amounts supplied by inorganic fertilizer. This
      ratio was 7% for the N uptake by the second maize crop. The quality and quantity
      of maize were equally good with both types of fertilization. During the 2 years
      following sludge spreading, N leaching remained as low in the sludged plot as in
      the inorganically fertilized one. The Cu, Zn, Cr, Cd, Pb and Ni composition of
      the drainage water was affected by neither of the types of amendment. From the
      heavy-metal contents of the soil, water and maize monitored over 1 year in the
      field experiment and from literature data for cow manure and atmospheric
      emissions, a theoretical balance between crop soil heavy-metal input and output
      over one century was drawn up. The long-term impact of cow manure on Zn, Ni and
      Cr in soil is higher than that of the studied heat-dried sludge. Obviously,
      sludge tended to cause a strong increase in soil Cu storage, valued for these
      soils, which are otherwise very Cu deficient.

PMID- 15862840
TI  - Environmental assessment of mercury contamination from the Rwamagasa artisanal
      gold mining centre, Geita District, Tanzania.
AB  - This study presents the results of an environmental assessment of mercury (Hg)
      contamination in the Rwamagasa artisanal gold mining area, northwest Tanzania,
      and the potential downstream dispersion along the River Malagarasi to Lake
      Tanganyika. At the time of sampling, generally low concentrations of Hg (<0.05
      mg/kg) occurred in most cultivated soils although higher Hg (0.05-9.2 mg/kg) was
      recorded in urban soils and vegetable plot soils where these are impacted by Hg
      contaminated water and sediment derived from mineral processing activities. Hg in
      vegetable and grain samples is mostly below the detection limit of 0.004 mg/kg
      Hg, apart from 0.007 and 0.092 mg/kg Hg in two yam samples and 0.011 to 0.013
      mg/kg Hg in three rice samples. The standardized (i.e., standardized to 10 cm
      length) Hg concentrations in Clarias spp. increase from about 0.01 mg Hg/kg for
      the River Malagarasi delta to 0.07, 0.2, and 1.6 mg/kg, respectively, for the
      Rwamagasa 'background', moderately and most contaminated sites. For piscivorous
      (Lates, Brycinus, and Hydrocynus spp.), insectivorous (Barbus spp.), and
      planktivorous (Haplochromis spp.) fish species, the 10-cm standardized Hg
      concentrations increase from about 0.006 mg/kg for the River Malagarasi-Lake
      Tanganyika area to 0.5 and 3.5 mg/kg, respectively, for the Rwamagasa moderately
      and most contaminated sites. The low concentrations of Hg in fish from the
      Malagarasi River delta and Lake Tanganyika indicate that Hg contamination from
      the Rwamagasa area does not have a readily discernible impact on the biota of
      Lake Tanganyika. Many of the fish samples from Rwamagasa exceed guidelines for
      human consumption (0.5 mg/kg) as well as the WHO recommended limit for vulnerable
      groups (0.2 mg/kg). Tissue total Hg (THg) of all fish collected from the River
      Malagarasi-Lake Tanganyika subarea is well below these guidelines. Potential
      human exposure through consumption of 300 g/day of rice grown on Hg-contaminated
      soils is 5.5 microg/week. Consumption of 250 g Nile perch (Lates spp.), 500 g
      tilapia (Oreochromis spp.), and 250 g of catfish (Clarias spp.) each week would
      result in an intake of 65 microg Hg/week for people consuming only fish from the
      Mara and Mwanza regions of Lake Victoria and 116 microg Hg/week for people in the
      Rwamagasa area consuming tilapia and Nile perch from Lake Victoria and catfish
      from mining-impacted streams. This is lower than the Provisional Tolerable Weekly
      Intake (PTWI) of 300 microg for Hg in the diet set by the WHO and the FAO.
      Inadvertent ingestion of soil containing 9 mg Hg/kg at a rate of 80 mg/day would
      give an additional estimated weekly intake of 5 microg THg, whereas the
      persistent and purposeful consumption of soil (geophagia) at a rate of 26 g
      soil/day would produce an additional chemical exposure of 230 microg Hg/day.

PMID- 15862841
TI  - Effects of metal mining effluent on Atlantic salmon (Salmo salar) and slimy
      sculpin (Cottus cognatus): using artificial streams to assess existing effects
      and predict future consequences.
AB  - In the summer of 2000, the effects of metal mine discharge on fish growth and
      exercise performance were assessed at a Zn-Pb-Cu mine in New Brunswick, Canada.
      Juvenile Atlantic salmon (Salmo salar) were exposed to 0%, 20%, and 80% treated
      metal mine effluent in a mobile, fish-only artificial stream system. Fish were
      fed commercial salmon pellets throughout the study. Young-of-the-year slimy
      sculpins (Cottus cognatus) were exposed to the same treatments in a multitrophic
      level, modular artificial stream system or mesocosm, in which the fish were
      dependent on seeded algae and invertebrates for nutrition. Treatment
      concentrations were chosen to represent existing discharge dilutions (80%) and a
      scenario of reduced effluent discharge (20%) as predicted upon mine closure
      (scheduled for 2008). Al, Ba, B, Fe, Mn, Sr, Tl, Ti, and Zn increased in a
      concentration-dependent fashion across the three treatments. Salmon body burdens
      of Ba, Cd, Li, Cu, Mn, Se, Sr, and Zn were increased in the 80% treatment, while
      Tl increased across all treatment levels. Mortalities and depressions in growth
      in both fish species paralleled treatment concentrations (80%>20%>0%). Salmon
      liver weight was significantly greater in fish exposed to 20% and 80% effluent in
      a concentration-dependent fashion. Exercise performance in fish, as assessed by
      the ability to recover from forced exercise, showed little effect of treatment.
      The contamination of the receiving environment by mine discharges has led to loss
      of fish, making it impossible to study the system in situ. However, the use of
      the artificial stream systems enabled us to assess effects of present conditions
      on fish, as well as the potential impacts of mine reclamation. The 20% discharge
      predicted following mine reclamation is potentially favourable for the
      reinstitution of native fishes into the system.

PMID- 15862842
TI  - Effects of season and low-level air pollution on physiology and element content
      of lichens from the U.S. Pacific Northwest.
AB  - Lichens were collected from three low-elevation sites in the western Cascade
      Range: HJ Andrews, OR (clean) and Bull Run, OR, and Pack Forest, WA (moderately
      enhanced nitrogen and sulfur deposition). The latter sites were within 50 km of
      Portland and Seattle/Centralia urban-industrial areas, respectively. Tissue
      concentrations of sulfur, nitrogen, and other macronutrients; rates of net carbon
      uptake; concentrations of photosynthetic pigments; and thallus density were
      correlated with season and seasonal changes in Platismatia glauca. Ion
      concentrations in precipitation and total wet deposition were measured from
      natural settings. Concentrations of depositional ions in precipitation, including
      NO3- and NH4+, were generally highest at Bull Run and Pack Forest; SO4(2-)
      concentrations and acidity were highest at Pack Forest. Total wet deposition was
      higher in the winter rainy season than the dry summer season at all three sites.
      Lichens adapted physiologically and morphologically to the higher light intensity
      and the warm, dry climate of summer through decreased optimal water content for
      CO2 uptake, increased concentrations of carotenoids and increased thallus
      density. Compared to the clean site, the sites with enhanced deposition were
      associated in P. glauca with year-round higher tissue concentrations of N, S, K,
      and Na; higher concentrations of total chlorophyll and carotenoids; higher
      OD435/415 ratios; higher CO2 uptake and lower thallus density in summer; and a
      general absence of other sensitive lichens. These results indicate that moderate
      levels of fertilizing air pollutants can stimulate carbon uptake and provide
      protection against chlorophyll degradation in air pollution-tolerant lichens of
      the Pacific Northwest, especially during the dry summer season.

PMID- 15862843
TI  - Indoor and outdoor concentrations of ultrafine particles in some Scandinavian
      rural and urban areas.
AB  - The concentration of ultrafine particles (0.01 to greater than 1 microm) was
      measured in some rural and urban areas of Sweden and Denmark. The instruments
      used are handheld real-time condensation particle counters, models CPC 3007 and P
      Trak 8525, both manufactured by TSI. Field measurements in Sweden were conducted
      in a few residential and office buildings, while in Denmark the measurement sites
      comprised two office buildings, one of them located in a rural area. The
      concentration of UFPs was measured simultaneously indoors and outdoors with
      condensation particle counters. The results revealed that the outdoor-generated
      particle levels were major contributors to the indoor particle number
      concentration in the studied buildings when no strong internal source was
      present. The results showed that in office buildings, the UFP concentrations
      indoors were typically lower and correlated fairly well to the number
      concentration outdoors. The determined indoor-outdoor ratios varied between 0.5
      and 0.8. The indoor levels of UFPs in offices where smoking is allowed was
      sometimes recorded higher than outdoor levels, as in one of the Danish offices.
      In residential buildings, the indoor number concentration was strongly influenced
      by several indoor activities, e.g., cooking and candle burning. In the presence
      of significant indoor sources, the indoor/outdoor (IO) ratio exceeded unity. The
      magnitude of UFP concentrations was greater in the large city of Copenhagen
      compared to the medium-size city of Gothenburg and lowest at more rural sites.

PMID- 15862844
TI  - Characterisation of urban catchment suspended particulate matter (Auckland
      region, New Zealand); a comparison with non-urban SPM.
AB  - Suspended particulate matter (SPM) is an important transport agent for metal
      contaminants in streams, particularly during high flow periods such as storm
      events. For highly contaminated urban catchments in the greater Auckland (New
      Zealand) area, trace metal partitioning between the dissolved phase and SPM was
      determined, and SPM characterised in terms of its Si, Al, Fe, Mn, Zn, Cu, Pb,
      TOC, TON and PO(4) concentrations, as well as particle size, abundance, type and
      surface area. This data was compared to similar data from representative non
      urban catchments in the Auckland region, the Kaipara River and Waikato River
      catchments, to identify any significant differences in the SPM and its potential
      trace metal adsorption capacity. Trace metal partitioning was assessed by way of
      a distribution coefficient: K(D)=[Me(SPM)]/[Me(DISS)]. Auckland urban SPM
      comprises quartz, feldspars and clay minerals, with Fe-oxides and minor Mn
      oxides. No particles of anthropogenic origin, other than glass shards, were
      observed. No change in urban SPM particle size or SSA was observed with seasonal
      change in temperature, but the nature of the SPM was observed to change with flow
      regime. The abundance of finer particles, SSA and Al content of the SPM increased
      under moderate flow conditions; however, Si/Al ratios remained constant,
      confirming the importance of aluminosilicate detrital minerals in surface run
      off. The SPM Fe content was observed to decrease with increased flow and was
      attributed to dilution of SPM Fe-oxide of groundwater origin. The Kaipara River
      SPM was found to be mineralogically, chemically and biologically similar to the
      urban SPM. However, major differences between urban catchment SPM and SPM from
      the much larger (non-urban) Waikato River were observed, and attributed to a
      higher abundance of diatoms. The Fe content of the Waikato River SPM was
      consistently lower (<5%), and the Si/Al ratio and Mn content was higher. Such
      differences observed between urban and non-urban SPM did not appear to affect the
      partitioning of Zn and Cu; however, Pb in the Kaipara and Waikato Rivers was
      found to be more associated with the dissolved phase. This is likely to reflect
      higher particulate Pb inputs to urban systems.

PMID- 15862845
TI  - Elemental content of lichens of the Point Reyes Peninsula, northern California.
AB  - The Point Reyes peninsula in northern California is about 45 km northwest of San
      Francisco and occasionally receives air masses from the city contributing to haze
      and lowered visibility. Although gaseous pollutants are not a problem, fine
      particulates containing carbon and other elements are measurable at the park. In
      this study, five lichen species were sampled along a 40-km linear transect from
      southeast to northwest from the town of Bolinas at the southern end of the
      peninsula. Elevated levels of Na and S and the Na/S ratio at localities nearer
      the ocean confirmed there is a definite marine aerosol influence on lichen
      elemental content. Elevated potassium and mercury concentrations were also found
      at high elevation sites that intercept fog. However, arsenic and lead were found
      to decrease with distance from Bolinas along the transect, suggesting these two
      elements originate in the fine particulate haze that enters the park from San
      Francisco. Concentrations of elements were not at enriched levels for other
      lichen species. A possible local influence of roads on element content needs
      further study.

PMID- 15862846
TI  - Source apportionment of ambient VOCs in Delhi City.
AB  - Source apportionment using chemical mass balance (CMB) model was carried using a
      data set of 360 four hourly samples collected at 15 locations of five categories
      namely residential, commercial, industrial, traffic intersections and petrol
      pumps during August 2001-July 2002 in Delhi. The results indicate that emissions
      from diesel internal combustion engines dominate in Delhi. Vehicular exhaust and
      evaporative emissions also contribute significantly to VOCs in ambient air.
      Emission of VOCs associated with sewage sludge was also found to contribute to
      VOCs in Delhi's air. This points to the fact that open defecation and leaking
      sewage manholes are a problem in all categories of locations.

PMID- 15862847
TI  - Characterization of atmospheric mineral components of PM2.5 in Beijing and
      Shanghai, China.
AB  - Weekly PM2.5 samples were collected for one year in Beijing and Shanghai and the
      crustal elements analyzed to investigate the concentration levels and temporal
      variations of ambient fine mineral dust. The mass concentrations of Al, Si, Ca,
      Mg, and Fe exhibited similar significant weekly variations in both Beijing and
      Shanghai. The annual average PM2.5 concentrations of major crustal elements
      ranged from 0.27 microg m-3 Mg to 2.48 microg m-3 Si in Beijing, which were 1.40
      2.24 times higher than those in Shanghai. Their PM-weighted values were
      comparable between the two cities. A distinct seasonal pattern was present for
      these crustal elements with the highest concentrations during the spring in
      Beijing and during the winter in Shanghai, and the lowest concentrations during
      the summer in both cities. During the dusty spring of 2000 in Beijing, soil dust
      was the second most abundant PM2.5 constituent with a contribution as high as
      18.6%, over twice that in the winter. The highest fine soil concentration (37.8
      microg m-3) and mass percentage (41.6%) occurred in the same week of intensive
      dust events impacting Beijing. The impact of dust storms complicates the goal of
      reducing PM2.5 in Beijing. Ca originating from construction activities appears to
      be a significant PM2.5 contributor as well.

PMID- 15862848
TI  - Elemental analyses of pine bark and wood in an environmental study.
AB  - Bark and wood samples were taken from the same individuals of Scots pine (Pinus
      sylvestris L.) from a polluted area close to a Cu-Ni smelter in Harjavalta and
      from some relatively unpolluted areas in western Finland. The samples were
      analysed by thick-target particle induced X-ray emission (PIXE) after
      preconcentration by dry ashing at 550 degrees C. The elemental contents of pine
      bark and wood were compared to study the impact of heavy metal pollution on pine
      trees. By comparison of the elemental contents in ashes of bark and wood, a
      normalisation was obtained. For the relatively clean areas, the ratios of the
      concentration in bark ash to the concentration in wood ash for different elements
      were close to 1. This means that the ashes of Scots Pine wood and bark have quite
      similar elemental composition. For the samples from the polluted area the mean
      concentration ratios for some heavy metals were elevated (13-28), reflecting the
      effect of direct atmospheric contamination. The metal contents in the ashes of
      pine bark and wood were also compared to recommendations for ashes to be recycled
      back to the forest environment. Bark from areas close to emission sources of
      heavy metal pollution should be considered with caution if aiming at recycling
      the ash. Burning of bark fuel of pine grown within 6 km of the Cu-Ni smelter is
      shown to generate ashes with high levels of Cu, Ni as well as Cd, As and Pb.

PMID- 15862849
TI  - Groundwater salinization in the Saloum (Senegal) delta aquifer: minor elements
      and isotopic indicators.
AB  - The hydrochemistry of minor elements bromide (Br), boron (B), strontium (Sr),
      environmental stable isotopes (18O and 2H) together with major-ion chemistry
      (chloride, sodium, calcium) has been used to constrain the source(s), relative
      age, and processes of salinization in the Continental Terminal (CT) aquifer in
      the Saloum (mid-west Senegal) region. Seventy-one groundwater wells which include
      24 wells contaminated by saltwater and three sites along the hypersaline Saloum
      River were sampled to obtain additional information on the hydrochemical
      characteristics of the groundwater defined in previous studies. Use of Br against
      Cl confirms the Saloum River saline water intrusion up to a contribution of 7%
      into the aquifer. In addition to this recent intrusion, a relatively ancient
      intrusion of the Saloum River water which had reached at least as far as 20 km
      south from the source was evidenced. The high molar ratio values of Sr/Cl and
      Sr/Ca indicate an additional input of strontium presumably derived from carbonate
      precipitation/dissolution reactions and also via adsorption reactions. The
      variable B concentrations (7-650 microg/L) found in the groundwater samples were
      tested against the binary mixing model to evaluate the processes of salinization
      which are responsible for the investigated system. Sorption of B and depletion of
      Na occur as the Saloum river water intrudes the aquifer (salinization) in the
      northern part of the region, whereas B desorption and Na enrichment occur as the
      fresh groundwater flushing displaces the saline waters in the coastal strip
      (refreshening). In the central zone where ancient intrusion prevailed, the
      process of freshening of the saline groundwater is indicated by the changes in
      major-ion chemistry as well as B desorption and Na enrichment. In addition to
      these processes, stable isotopes reveal that mixing with recently infiltrating
      waters and evaporation contribute to the changes in isotopic signature.

PMID- 15862850
TI  - Chemical characterization of individual particles (PM10) from ambient air in
      Guiyang City, China.
AB  - PM10 samples were collected during 5 days in Guiyang, China in July 2003. A total
      of about 2300 particles was analyzed by an automated Scanning Electron Microscope
      with Energy-Dispersive Spectrometer (SEM-EDS). Hierarchical cluster analysis
      (HCA) was used to identify different particle types that occurred in the aerosol.
      Seventeen particle types were identified and presented in the order of decreasing
      number abundance as: silicomanganese slag, soil and fly ash, coal burning,
      silicomanganese, quartz, syngenite, S-bearing iron, calcium rich, gypsum,
      sphalerite, dolomite, iron, alloy, lead sulfate, zinc rich, sulfur-rich particles
      and aluminum manufacturing dust. The majority of the particles in the studied
      size range are of anthropogenic origin, especially from metallurgical industry.
      The study illustrates the complexity of particle pollution in air of an
      industrial Chinese city and the results should be useful in planning mitigation
      measures.

PMID- 15862851
TI  - On the association between high temperature and mortality in warm climates.
AB  - We conducted a time-series analysis of 1997-1999 data records of air temperature
      and all-cause mortality in Greater Beirut, using bi-linear Poisson auto
      regressive models, and published our findings in the Science of the Total
      Environment [El-Zein, A., Tewtel-Salem, M., Nehme, G., 2004. A time-series
      analysis of mortality and air temperature in Greater Beirut. Sci. Total Environ.
      330, 71-80]. We compared our results to those of Curriero et al. [Curriero, F.C.,
      Heiner, K.S., Samet, J.M., Zeger, S.L., Strug, L., Patz, J.A., 2002. Temperature
      and mortality in 11 cities of the Eastern United States. Am. J. Epidemiol. 155(1)
      80-87.], who subsequently reported that their original results were inaccurate
      and published new results [Curriero, F.C., Heiner, K.S., Samet, J.M., Zeger,
      S.L., Strug, L., Patz, J.A., 2002. Temperature and mortality in 11 cities of the
      Eastern United States. Am. J. Epidemiol. 155(1) 80-87; Curriero, F.C., Samet,
      J.M., Zeger, S.L., 2003. Letter to the Editor re. On the Use of Generalized
      Additive Models in Time-Series Studies of Air Pollution and Health" and
      "Temperature and Mortality in 11 Cities of the Eastern United States". Am. J.
      Epidemiol. 158(1) 93-94.]. In this letter, we report two changes in the
      interpretation of our findings as a result of the change in the results of
      Curriero et al. [Curriero, F.C., Heiner, K.S., Samet, J.M., Zeger, S.L., Strug,
      L., Patz, J.A., 2002. Temperature and mortality in 11 cities of the Eastern
      United States. Am. J. Epidemiol. 155(1) 80-87]. Their newly-reported results
      reinforce our conclusion that heat-related mortality can be a significant public
      health issue even in temperate to warm climates. However, our findings raise a
      question concerning the ability of socioeconomic indicators to explain
      differences in vulnerability to heat between high-income and low-income
      countries.

PMID- 15862852
TI  - Impaired oral reading in two atypical dyslexics: a comparison with a
      computational lexical-analogy model.
AB  - A computational model of reading was developed based upon the notion that the
      structural relationship between orthography and phonology is of greater
      importance than the dimension of semantics for the reading aloud of single words.
      Degradation of this model successfully simulated the reading performance of two
      patients with atypical acquired dyslexia. The first patient CAV, studied and
      described in the literature by Warrington in 1981, presented with unusual
      concrete word dyslexia, i.e., he had a category-specific reading deficit for
      concrete words compared with abstract words. The second patient BG is a
      phonological dyslexic who, although displaying a strong concreteness effect
      (concrete words read better than abstract words), was able to read functors
      individually perfectly well, a pattern that is rarely if ever seen. The
      computational model was used to generate a set of words for which it was
      predicted that BG would show no concreteness effect. The results of BG's reading
      of these words were consistent with this prediction, thereby providing greater
      support for the validity of the model. It is concluded that a computational
      approach that attempts not only to reproduce the core symptoms of the major
      varieties of acquired dyslexia but also to simulate clinical data from specific
      patients has much to contribute to the understanding of cognitive deficits and to
      the design of effective rehabilitation strategies.

PMID- 15862853
TI  - Spontaneous humor among right hemisphere stroke survivors.
AB  - We analyzed spontaneous conversational humor production and response among 11
      right hemisphere-damaged (RHD) patients, 10 left hemisphere-damaged (LHD)
      patients, 7 normal controls (NC), and their spouses. RHD patients and their
      spouses reported a statistically significant decline in the patients' orientation
      to humor post-stroke. Also, we found a significant positive association between a
      RHD patient's ability to decode prosody and their self-reported orientation to
      humor post-stroke.

PMID- 15862854
TI  - Electrophysiological indices of brain activity to "the" in discourse.
AB  - In a first experiment, we recorded event-related-potentials (ERPs) to "the"
      followed by meaningful words (Story) versus "the" followed by nonsense syllables
      (Nonse). Left and right lateral anterior positivities (LAPs) were seen from the
      onset of "the" up to 200 ms in both conditions. Later than 200 ms following the
      onset of "the", the left and right LAPs continued for "the" in the Story, but
      were replaced by a negativity in the Nonse Condition. In a second experiment,
      ERPs were recorded to "the" in the Story and Nonse contexts mixed together under
      two different task instructions (attend to the auditory stimuli versus ignore the
      auditory stimuli). The same pattern of findings as Experiment 1 were observed for
      the Story and Nonse contexts when the participants attended to the auditory
      stimuli. Ignoring the auditory stimuli led to an attenuation of the right LAP,
      supporting the hypothesis that it is an index of discourse processing.

PMID- 15862855
TI  - Repetition priming within and between the two cerebral hemispheres.
AB  - Two experiments explored repetition priming benefits in the left and right
      cerebral hemispheres. In both experiments, a lateralized lexical decision task
      was employed using repeated target stimuli. In the first experiment, all targets
      were repeated in the same visual field, and in the second experiment the visual
      field of presentation was switched following repetition. Both experiments
      demonstrated hemispheric specialization for the task (a RVF advantage for word
      identification) and hemispheric interaction for word processing (lexicality
      priming from contralateral distracters). In the first experiment, words were
      identified more quickly and accurately following repetition, with repetition
      facilitating faster but fewer correct responses for non-words. Complex
      interactions between visual field of first and second presentation in the second
      experiment indicate asymmetric interhemispheric repetition priming effects. These
      results provide a broad picture of hemispheric asymmetries in word processing and
      of complex interaction between the hemispheres during word recognition.

PMID- 15862856
TI  - Unilateral brain damage effects on processing homonymous and polysemous words.
AB  - Using an auditory semantic priming paradigm, the present study investigated the
      abilities of left-hemisphere-damaged (LHD) non-fluent aphasic, right-hemisphere
      damaged (RHD) and normal control individuals to access, out of context, the
      multiple meanings of three types of ambiguous words, namely homonyms (e.g.,
      "punch"), metonymies (e.g., "rabbit"), and metaphors (e.g., "star"). In addition,
      the study tested certain predictions of the "suppression deficit" and "coarse
      semantic coding" hypotheses that have been proposed to account for the linguistic
      deficits typically observed after RH damage. Homonymous, metonymous, and
      metaphorical words were used as primes followed after a short (100 ms) or a long
      (1000 ms) inter-stimulus interval (ISI) by dominant-meaning-related, subordinate
      meaning-related or unrelated target words. No significant group effects were
      found, and for both ISIs, dominant- and subordinate-related targets were
      facilitated relative to unrelated control targets for the homonymy and metonymy
      conditions. In contrast, for the metaphor condition, only targets related to the
      dominant meaning were facilitated. These findings provide only partial support
      for the "suppression deficit" hypothesis and no support for the "coarse semantic
      coding" hypothesis (as interpreted herein) indicating that patients with focal LH
      or RH damage can access the multiple meanings of ambiguous words and exhibit
      processing abilities comparable to those of older normal control subjects, at
      least at the single-word level.

PMID- 15862857
TI  - Hemispheric processing of anaphoric inferences: the activation of multiple
      antecedents.
AB  - This research investigates the hemispheric processing of anaphors when readers
      activate multiple antecedents. Participants read texts promoting an anaphoric
      inference and performed a lexical decision task to inference-related target words
      that were consistent (Experiment 1) or inconsistent (Experiment 2) with the text.
      These targets were preceded by constrained or less constraining text and were
      presented to participants' right visual field-left hemisphere or to their left
      visual field-right hemisphere. In Experiment 1, both hemispheres showed
      facilitation for consistent antecedents and the right hemisphere showed an
      advantage over the left hemisphere in processing antecedents when preceded by
      less constrained text. In Experiment 2, the left hemisphere only showed negative
      facilitation for inconsistent antecedents. When readers comprehend text with
      multiple antecedents: both hemispheres process consistent information, the left
      hemisphere inhibits inconsistent information, and the right hemisphere processes
      less constrained information.

PMID- 15862858
TI  - Positive facial affect facilitates the identification of famous faces.
AB  - Several convergent lines of evidence have suggested that the presence of an
      emotion signal in a visual stimulus can influence processing of that stimulus. In
      the current study, we picked up on this idea, and explored the hypothesis that
      the presence of an emotional facial expression (happiness) would facilitate the
      identification of familiar faces. We studied two groups of normal participants
      (overall N=54), and neurological patients with either left (n=8) or right (n=10)
      temporal lobectomies. Reaction times were measured while participants named
      familiar famous faces that had happy expressions or neutral expressions. In
      support of the hypothesis, naming was significantly faster for the happy faces,
      and this effect obtained in the normal participants and in both patient groups.
      In the patients with left temporal lobectomies, the effect size for this
      facilitation was large (d=0.87), suggesting that this manipulation might have
      practical implications for helping such patients compensate for the types of
      naming defects that often accompany their brain damage. Consistent with other
      recent work, our findings indicate that emotion can facilitate visual
      identification, perhaps via a modulatory influence of the amygdala on
      extrastriate cortex.

PMID- 15862860
TI  - Word length effect in early reading and in developmental dyslexia.
AB  - Vocal reaction times were measured in Italian dyslexics and in proficient readers
      while they read single words. Three groups of control participants (for a total
      of 79) were tested. All were in the first, second or third grade of elementary
      school. Nine third graders with a low level of reading ability when assessed by
      standard reading procedures were also tested. Results indicated that vocal RTs of
      control participants were faster and less sensitive to word length as a function
      of age; also, there was a particularly marked change between first and second
      graders. Dyslexics' vocal RTs and errors were much worse than those of peer
      control participants and resembled those of first grade controls. It is suggested
      that normal readers in an orthographically transparent language (Italian) adopt a
      lexical strategy quite early in their learning. On the contrary, dyslexics seem
      unable to learn this mode of processing and continue to use a sub-lexical reading
      procedure.

PMID- 15862859
TI  - Idiom comprehension deficits in relation to corpus callosum agenesis and
      hypoplasia in children with spina bifida meningomyelocele.
AB  - Idioms are phrases with figurative meanings that are not directly derived from
      the literal meanings of the words in the phrase. Idiom comprehension varies with:
      literality, whether the idiom is literally plausible; compositionality, whether
      individual words contribute to a figurative meaning; and contextual bias. We
      studied idiom comprehension in children with spina bifida meningomyelocele (SBM),
      a neurodevelopmental disorder associated with problems in discourse comprehension
      and agenesis and hypoplasia of the corpus callosum. Compared to age peers,
      children with SBM understood decomposable idioms (which are processed more like
      literal language) but not non-decomposable idioms (which require contextual
      analyses for acquisition). The impairment in non-decomposable idioms was related
      to congenital agenesis of the corpus callosum, which suggests that the
      consequences of impaired interhemispheric communication, whether congenital or
      acquired in adulthood, are borne more by configurational than by compositional
      language.

PMID- 15862862
TI  - Complex between triple helix of collagen and double helix of DNA in aqueous
      solution.
AB  - We demonstrate in this paper that one example of a biologically important and
      molecular self-assembling complex system is a collagen-DNA ordered aggregate
      which spontaneously forms in aqueous solutions. Interaction between the collagen
      and the DNA leads to destruction of the hydration shell of the triple helix and
      stabilization of the double helix structure. From a molecular biology point of
      view this nano-scale self-assembling superstructure could increase the stability
      of DNA against the nucleases during collagen diseases and the growth of collagen
      fibrills in the presence of DNA.

PMID- 15862861
TI  - The binding of novel two-color fluorescence probe FA to serum albumins of
      different species.
AB  - The novel two-color ratiometric fluorescence probe FA belonging to a class of 3
      hydroxychromone dyes was applied for characterization of binding sites in serum
      albumins obtained from seven species (bovine, dog, horse, human, pig, rabbit and
      sheep). On strong and highly specific FA binding to the same location in protein
      structure, the species-dependent differences were observed in positions of
      absorption maxima, positions of two fluorescence emission bands and the intensity
      ratios between them. They were analyzed by multiparametric algorithm that allowed
      a detailed characterization of probe-binding sites and were characterized by very
      low polarity, high electronic polarizability and different extent of
      intermolecular hydrogen bonding. The species-dependent differences were also
      observed in time-resolved fluorescence emission decays. Fluorescence competition
      experiments with the drug warfarin, suggested the location of FA binding site
      within or in proximity to Domain IIA.

PMID- 15862863
TI  - Phase diagram of the system sodium alginate/water: a model for biofilms.
AB  - Sodium alginate is a polyelectrolyte consisting of the monomer units beta-D
      mannuronate and alpha-L-guluronate. Mainly based on the theory of Khokhlow et
      al., the state diagram of the binary system alginate/water has been calculated
      using different sets of parameters like degree of ionization, degree of
      polymerization and interaction function. The calculations comprise miscibility
      gaps, liquidus curves, eutectic points and the behaviour at temperatures below
      the melting point of water. Also gel and swelling curves have been treated, where
      gels are physically crosslinked. The DSC diagram of a 0.5 by wt.% polymer sol
      shows a double melting peak, which is explained by a heterogeneity above 0
      degrees C. The crystallization of water seems to concentrate the gelled system
      irreversibly.

PMID- 15862864
TI  - Artificial chaperone-assisted refolding of chemically denatured alpha-amylase.
AB  - It is now well established that alpha-cyclodextrin (alpha-CD) is a valuable
      folding agent in refolding processes of several denatured enzyme solutions. The
      refolding of Gu-HCl denatured alpha-amylase in the dilution-additive mode
      revealed that alpha-CD enhanced the refolding yield by 20-30% depending upon
      alpha-CD concentration. However, the refolding efficiency of the Gu-HCl denatured
      alpha-amylase through the artificial chaperone-assisted method indicated that
      alpha-CD enhanced the activity recovery of denatured alpha-amylase by almost 50%
      and also increased the reactivation rate constant relative to the unassisted
      control sample. The higher refolding efficiency should be due to different
      mechanism played by alpha-CD in this technique. In addition, our data indicated
      that higher refolding yields are obtained when the residual Gu-HCl concentration
      is low in the refolding environment and when the capture agent is removed not in
      a stepwise manner from the protein-detergent complexes in the stripping step of
      the whole process. Collectively, the results of this investigation expand the
      range of procedural variations used to refold different denatured proteins
      through artificial chaperone-assisted method.

PMID- 15862865
TI  - Muscle contraction: a new interpretation of the transient behaviour of muscle.
AB  - Piazzesi et al. [G. Piazzesi, L. Lucii, V. Lombardi, J. Physiol. 545 (2002) 145
      151] made a study on the muscle transients due to step changes in force using
      improved time resolution and recorded filament movement and shortening velocities
      in the four phases. They point to Phase 2 and to Phase 4 (working muscle) and
      claim that their results do not contradict the swinging-cross-bridge (SCB) model
      which has a much-quoted constant power stroke of about 150 A (their value of 70 A
      was smaller). Siding with the SCB model, they nevertheless record that the power
      stroke decreases with load. We are pleased with this experimental result as it
      conforms to our theory, published in 1996, of an impulsive model with a much
      smaller step-size distance z (approximately 20 A). Using their data we obtain
      precise interval times and estimates of filament movement in Phase 2 and in
      working muscle. Our first result is that the time frames (interval times) for
      Phase 2 are the same as in working muscle. Moreover, we demonstrate that the
      authors' data verify the correctness of our calculated z values. There are eight
      active ATP events in Phase 2 in time frame t compared to one in working muscle in
      the same time frame t. This gives, for the first time, precise numbers for
      contractile events. We show that the SCB model is incorrect and our analysis
      supports the impulsive model with a much smaller filament (zero-load) motion,
      approximately 20 A per ATP split.

PMID- 15862866
TI  - IgA1 is the premier serum glycoprotein recognized by human galectin-1 since T
      antigen (Galbeta1-->3GalNAc-) is far superior to non-repeating N-acetyl
      lactosamine as ligand.
AB  - Human heart galectin-1 (HHL) was separated by high pressure liquid chromatography
      from endogenous glycoproteins co-purified with it during affinity chromatography.
      These glycoproteins offered excellent ligands for HHL binding and were rich in T
      antigen (Galbeta1-->3 GalNAc-) of O-linked oligosaccharides. In enzyme linked
      lectin assay and hemagglutination inhibition assay, human IgA1, bovine fetuin and
      other O-glycosylated T antigen-bearing glycoproteins bound to the lectin
      efficiently in contrast to single N-acetyl lactosamine (LacNAc)-bearing N-linked
      oligosaccharides released from them and to IgG which is not O-glycosylated. HHL
      binding to IgA1 and fetuin was unaffected by removal of their N-linked
      oligosaccharides by alpha-mannosidase. When immobilized, O-glycosylated serum
      proteins but not IgG could capture HHL from its solutions. Desialylated or
      polymeric IgA1 was better inhibitor than monomeric IgA1. The findings suggest a
      possible role for galectin-1 in anchoring of microbial and cancer cells known to
      be rich in T antigen, in high serum IgA1 turn over and in tissue sequestering of
      IgA1 immune complexes especially after their microbial desialylation in IgA
      nephropathy and other immune complex-mediated disorders.

PMID- 15862867
TI  - New 4-O-substituted xylosyl units in the xyloglucan from leaves of Hymenaea
      courbaril.
AB  - A homogeneous fucogalactoxyloglucan, isolated from the leaves of Hymenaea
      courbaril, was analysed by methylation-GC-MS. These procedures involved derived
      partially O-methylated alditol acetates and acetylated aldononitriles, which
      demonstrated the presence of both 2-O- and 4-O-substituted Xylp units in the side
      chains. The presence of the unusual, latter structure was confirmed by 2D NMR
      spectroscopy with a correlated HMQC C-4/H-4 signal at delta 77.8/3.73. A similar
      4-O-substituted xylosyl structure was present in a decasaccharide Glc4Xyl3Gal2Fuc
      obtained via endo-glucanase treatment of the polysaccharide, which gave rise to a
      molecular ion with m/z 1555 (ESI-MS, Na+ form).

PMID- 15862869
TI  - Human rights audit of mental health legislation--results of an Australian pilot.

PMID- 15862870
TI  - The European convention and mental health law in England and Wales: moving beyond
      process?

PMID- 15862871
TI  - What does the "right to health" have to offer mental health patients?

PMID- 15862872
TI  - The right to treatment of persons with psychosocial disabilities and the role of
      the courts.

PMID- 15862873
TI  - Collaborative research trials: a strategy for fostering mental health protections
      in developing nations.

PMID- 15862874
TI  - Can international law improve mental health? Some thoughts on the proposed
      convention on the rights of people with disabilities.
AB  - This paper examines the promise of the proposed Convention on the Rights of
      People with Disabilities to improve the position of people with mental illness.
      Proponents of the new Disability Convention argue that the state of human rights
      abuses experienced by people with disabilities is intolerable, that the existing
      international law is inadequate, that additional international law will increase
      the visibility of people with disabilities and will clarify the fundamental
      entitlement to equality, and that, as a result, the position of people with
      disabilities will be greatly enhanced. This paper questions the value of
      international law to achieve real change and warns against placing too much faith
      in the law. The potential of a new international law to rectify the wrongs
      experienced by people with psychiatric disabilities will depend on whether the
      new law specifically displaces the existing international law which undermines
      the rights of people with mental illness and on the final terms of the Convention
      with respect to recognition and enforcement. Ironically, it is the process of
      developing the Convention which has been empowering, and the utility of the new
      law will ultimately turn on the continuation of the momentum built through this
      process.

PMID- 15862875
TI  - Development of an integrated model for heat transfer and dynamic growth of
      Clostridium perfringens during the cooling of cooked boneless ham.
AB  - Numerous small meat processors in the United States have difficulties complying
      with the stabilization performance standards for preventing growth of Clostridium
      perfringens by 1 log10 cycle during cooling of ready-to-eat (RTE) products. These
      standards were established by the Food Safety and Inspection Service (FSIS) of
      the US Department of Agriculture in 1999. In recent years, several attempts have
      been made to develop predictive models for growth of C. perfringens within the
      range of cooling temperatures included in the FSIS standards. Those studies
      mainly focused on microbiological aspects, using hypothesized cooling rates.
      Conversely, studies dealing with heat transfer models to predict cooling rates in
      meat products do not address microbial growth. Integration of heat transfer
      relationships with C. perfringens growth relationships during cooling of meat
      products has been very limited. Therefore, a computer simulation scheme was
      developed to analyze heat transfer phenomena and temperature-dependent C.
      perfringens growth during cooling of cooked boneless cured ham. The temperature
      history of ham was predicted using a finite element heat diffusion model.
      Validation of heat transfer predictions used experimental data collected in
      commercial meat-processing facilities. For C. perfringens growth, a dynamic model
      was developed using Baranyi's nonautonomous differential equation. The
      bacterium's growth model was integrated into the computer program using predicted
      temperature histories as input values. For cooling cooked hams from 66.6 degrees
      C to 4.4 degrees C using forced air, the maximum deviation between predicted and
      experimental core temperature data was 2.54 degrees C. Predicted C. perfringens
      growth curves obtained from dynamic modeling showed good agreement with validated
      results for three different cooling scenarios. Mean absolute values of relative
      errors were below 6%, and deviations between predicted and experimental cell
      counts were within 0.37 log10 CFU/g. For a cooling process which was in exact
      compliance with the FSIS stabilization performance standards, a mean net growth
      of 1.37 log10 CFU/g was predicted. This study introduced the combination of
      engineering modeling and microbiological modeling as a useful quantitative tool
      for general food safety applications, such as risk assessment and hazard analysis
      and critical control points (HACCP) plans.

PMID- 15862876
TI  - Developing microbial spoilage population in vacuum-packaged charcoal-broiled
      European river lamprey (Lampetra fluviatilis).
AB  - Microbiological and sensory changes in vacuum-packaged charcoal-broiled river
      lampreys from three lamprey processing plants were monitored as a function of
      time at 8 degrees C. The lampreys were examined every 7 days up to 8 weeks for
      aerobic plate count (APC) and lactic acid bacteria (LAB). The highest mean APC
      and LAB were 6.01 log CFU/g and 4.86 log CFU/g, respectively. Only 6 out of 15
      lots reached an APC value of 7.0 log CFU/g during storage. The sensory scores
      remained at the baseline levels after 8 weeks' storage. Twenty-seven isolates
      were randomly picked from MRS agar and identified to species level using a 16S
      and 23S rDNA HindIII RFLP (ribotyping) database and sequencing of the 16S rRNA
      gene if no database match was obtained. Twelve of the 27 isolates were identified
      as Lactobacillus curvatus subsp. curvatus, and two Leuconostoc mesenteroides and
      one Weissella halotolerans strain were also detected. Twelve isolates were not
      identified by the LAB database. However, they possessed very high (99.9%) 16S
      gene sequence similarity with either Staphylococcus warneri or Staphylococcus
      pasteuri type strains. The LAB detected, with the exception of W. halotolerans,
      have commonly been associated with spoilage of fishery products, but in these
      vacuum-packaged lampreys, they were not the dominant organisms within the
      developing spoilage population.

PMID- 15862877
TI  - Antiaflatoxigenic and antioxidant activities of Garcinia extracts.
AB  - The effect of hexane and chloroform extracts from the fruit rinds of Garcinia
      cowa and Garcinia pedunculata on the growth and aflatoxin production in
      Aspergillus flavus was studied using peanut powder as a model food system. The
      growth of A. flavus was completely inhibited by the hexane and chloroform
      extracts from G. cowa and chloroform extract from G. pedunculata at 3000 ppm
      concentration, which was considered as the minimum inhibitory concentration
      (MIC). The MIC for the hexane extract of G. pedunculata was at 4000 ppm. Both the
      extracts from G. cowa inhibited aflatoxin B1 production upto 100% at a lower
      concentration of 2000 ppm. It was observed that, at lower concentration of the
      extracts from G. cowa and G. pedunculata, the degree of inhibition of aflatoxin
      production was much higher than the inhibition of fungal growth. The hexane and
      chloroform extracts from G. cowa and G. pedunculata were also studied for their
      antioxidant capacity by the formation of phosphomolybdenum complex at 100 ppm
      concentration and reducing power by potassium ferricyanide reduction method at
      various concentrations. Hexane and chloroform extracts from G. cowa showed higher
      antioxidant capacity than G. pedunculata extracts. Similarly, both the extracts
      from G. cowa showed higher reducing power than the extracts from G. pedunculata.
      The antiaflatoxigenic activities of the extracts from G. cowa and G. pedunculata
      may be due to their effective antioxidative properties, which could suppress the
      biosynthesis of aflatoxin.

PMID- 15862878
TI  - Study of benzoate, propionate, and sorbate salts as mould spoilage inhibitors on
      intermediate moisture bakery products of low pH (4.5-5.5).
AB  - A hurdle technology approach has been applied to control common mold species
      causing spoilage of intermediate moisture bakery products (Eurotium spp.,
      Aspergillus spp., and Penicillium corylophilum), growing on a fermented bakery
      product analogue (FBPA). The factors studied included a combination of different
      levels of weak acid preservatives (potassium sorbate, calcium propionate, and
      sodium benzoate; 0-0.3%), pH (4.5-5.5), and water activity (a(w); 0.80-0.90).
      Potassium sorbate was found to be the most effective in preventing fungal
      spoilage of this kind of products at the maximum concentration tested (0.3%)
      regardless of a(w). The same concentration of calcium propionate and sodium
      benzoate was effective only at low a(w) levels. On the other hand, potassium
      sorbate activity was slightly reduced at pH 5.5, the 0.3% being only effective at
      0.80 a(w). These findings indicate that potassium sorbate may be a suitable
      preserving agent to inhibit deterioration of a FBPA of slightly acidic pH (near
      4.5) by xerophilic fungi. Further studies have to be done in order to adjust the
      minimal inhibitory concentration necessary to obtain a product with the required
      shelf life.

PMID- 15862879
TI  - An attempt to optimize potassium sorbate use to preserve low pH (4.5-5.5)
      intermediate moisture bakery products by modelling Eurotium spp., Aspergillus
      spp. and Penicillium corylophilum growth.
AB  - Mould growth was modelled on fermented bakery product analogues (FBPA) of two
      different pH (4.5 and 5.5), different water activity (a(w)) levels (0.80-0.90)
      and potassium sorbate concentrations (0-0.3%) by using seven moulds commonly
      causing spoilage of bakery products (Eurotium spp., Aspergillus spp. and
      Penicillium corylophilum). For the description of fungal growth (growth rates) as
      a function of a(w), potassium sorbate concentration and pH, 10-terms polynomial
      models were developed. Modelling enables prediction of spoilage during storage as
      a function of the factors affecting fungal growth. At pH 4.5 the concentration of
      potassium sorbate could be reduced to some extent only at low levels of a(w),
      whereas at pH 5.5 fungal growth was observed even by adding 0.3% of potassium
      sorbate. However, this preservative could be a valuable alternative as antifungal
      in such bakery product, of slightly acidic pH, if a long shelf life has not to be
      achieved.

PMID- 15862880
TI  - Model for the combined effects of temperature, pH and sodium chloride
      concentration on survival of Shigella flexneri strain 5348 under aerobic
      conditions.
AB  - Shigella is recognized as a major foodborne pathogen; however, relatively few
      studies have been reported on its growth and survival characteristics,
      particularly under conditions relevant to food. A fractional factorial design was
      used to measure the effects and interactions of temperature (4-37 degrees C), pH
      (2-6) and NaCl (0.5-9%) on survival kinetics of Shigella flexneri strain 5348 in
      BHI broth. Stationary-phase cells were inoculated into sterile media to give
      initial populations of 6-7 log(10) CFU/ml and bacterial populations were
      determined periodically by aerobic plate counts. A total of 267 cultures,
      representing 83 variable combinations of temperature, pH and NaCl concentration,
      were analyzed. Survivor curves were fitted from plate count data by means of a
      two-phase linear model to determine lag times and slopes of the curves, from
      which decimal reduction times (D-values) and times to a 4-log10 inactivation (t
      4D) were calculated. Second order response surface models in terms of
      temperature, initial pH and NaCl concentration were obtained for the inactivation
      kinetics parameters of S. flexneri using regression analysis. The use of log10
      transformation of the inactivation kinetics parameters yielded models with R2
      values of >0.8. These models can provide an estimate of Shigella inactivation.
      The data obtained suggest that Shigella is resistant to acid and salt and that
      low pH foods stored at low temperatures may serve as vehicles for
      gastrointestinal illness.

PMID- 15862881
TI  - Fate of Listeria monocytogenes in experimentally contaminated French sausages.
AB  - Listeria monocytogenes has been recognized as one of the most important foodborne
      pathogens dealt with by the food. The bacterium has been found in every part
      along the pork processing industry from the slaughterhouse to the cutting room
      and the delicatessen factories. During the fermentation and drying of sausages,
      L. monocytogenes tends to decrease substantially. However, despite the various
      hurdles in the dry sausage manufacturing process, L. monocytogenes is able to
      survive and is detected in the final products. The present study has evaluated
      growth and survival of eight different L. monocytogenes strains (originating from
      sausage, sausage industry environment and from clinical cases of listeriosis) in
      experimentally inoculated French sausages with 10(4) cfu g(-1). This study points
      out the fact that the decrease of L. monocytogenes contamination rate during the
      manufacturing process of sausages is strain dependent (p < 0.001) and mainly due
      to the drying and maturation step than to the fermentation itself. Whatever the
      strains studied, almost no decrease of the contamination rate was noted during
      the fermentation step. However hurdle-adapted strains (those isolated from
      sausages or sausage industry environment) were more difficult to cure from
      sausages (decrease by 1.5 log10) than non-adapted strains (decrease by 3 log10)
      at the end of the drying period (day 35), when sausages were ready for
      consumption. These sausages became safe only at the best before date. As a
      consequence, L. monocytogenes and more particularly those "adapted" strains might
      represent a very important issue for hygienists since these strains originating
      from sausages or production environment themselves are likely to contaminate
      sausages during manufacturing and remain in the final products. However, the high
      inoculum levels used in the study (10(4) cfu g(-1)) are not representative of the
      natural contamination of L. monocytogenes commonly encountered in the raw
      material for sausages. If such contamination happened to be inferior to 100 cfu
      g(-1), then the manufacturing process used in this study would be able to produce
      "safe" sausages according to the European regulation requiring the absence of L.
      monocytogenes in 25 g of food with a tolerance of below 100 cfu g(-1) at the best
      before date.

PMID- 15862882
TI  - Mode of action of lipid II-targeting lantibiotics.
AB  - The antimicrobial action of bacteriocins from Gram-positive bacteria is based on
      interaction with the cytoplasmic membrane of sensitive bacteria. Models based on
      studies with artificial membrane systems propose that nisin forms wedge-like
      poration complexes in the membrane by electrostatic interaction between the
      positively charged C terminus of the peptide and anionic membrane phospholipids.
      Nisin can also permeabilise membranes via a targeted mechanism by using lipid II,
      the bactoprenol-bound precursor of the bacterial cell wall, as a docking
      molecule. Another consequence of binding with lipid II is the inhibition of
      peptidoglycan biosynthesis. Mersacidine and actagardine also form a complex with
      lipid II, but binding only blocks the incorporation of lipid II into
      peptidoglycan, resulting in slow cell lysis rather than pore formation. Both
      peptides share a conserved sequence motif with plantaricin C and pediocin PD-1,
      which is most probably involved in the binding of these bacteriocins to lipid II.
      Although pediocin PD-1 and plantaricin C may inhibit peptidoglycan biosynthesis,
      pore formation is rather due to electrostatic interaction between the positively
      charged unbridged N-terminus and anionic phospholipids in the cytoplasmic
      membrane of sensitive cells. In the light of increased antibiotic resistance,
      this review focuses on the mode of action of lantibiotics that involve lipid II,
      possible candidates for the development of new-generation novel antibiotic drugs.

PMID- 15862883
TI  - Growth of Listeria monocytogenes on iceberg lettuce and solid media.
AB  - The growth of pathogenic bacterium Listeria monocytogenes on fresh-cut iceberg
      lettuce under constant temperatures was modelled in order to investigate
      microbial safety during distribution of this vegetable. We examined the effects
      of several incubation temperatures, ranging from 5 to 25 degrees C, on bacterial
      growth. These data were fitted to the Baranyi model and the curves showed a high
      correlation coefficient at all temperature (R2 > 0.95). In addition, the native
      bacterial flora of the lettuce did not affect the growth rate of L. monocytogenes
      regardless of incubation temperature. However, the lag time was reduced at a
      ratio of native bacteria to inoculated L. monocytogenes (100:1) at low incubation
      temperatures (5 and 10 degrees C). Furthermore, the maximum population density
      (MPD) was increased at a low ratio of native to inoculated L. monocytogenes (1:1)
      at all incubation temperatures. These results were compared with the previous
      work published by [Buchanan, R.L., Stahl, H.G., Whiting, R.C., 1989. Effects and
      interactions of temperature, pH, atmosphere, sodium chloride, and sodium nitrite
      on the growth of Listeria monocytogenes. J. Food Prot. 52, 844-851] that is being
      developed at the US Department of Agriculture (USDA) Agricultural Research
      Service's Pathogen Modelling Program (PMP). The broth-based Buchanan model for L.
      monocytogenes was found to markedly deviate from the observed data. In order to
      investigate this discrepancy, we examined the effects of medium environment and
      nutrient content on L. monocytogenes growth using tryptic soy agar plates (TSAP)
      and agar plates (AP) containing 1.7% sucrose. The inoculated bacteria on both
      TSAP and AP showed slower growth rates than that predicted by the PMP. The MPD of
      bacteria grown on TSAP was similar to the PMP model ( approximately 9 log10
      CFU/ml or plate (circle of diameter of 90 mm)) regardless of the incubation
      temperature. By contrast, the MPD observed on AP was approximately 4 log10 CFU
      lower than that observed on TSAP or predicted by the PMP. Both the growth rate
      and the MPD of L. monocytogenes on AP were similar to those on lettuce. These
      results suggest that the solid medium and poor nutrient content inhibited the
      growth of L. monocytogenes on lettuce. The growth rates of the inoculated L.
      monocytogenes on all media were described using Ratkowsky's simple square root
      model.

PMID- 15862884
TI  - Persistence of Escherichia coli O157:H7, Salmonella Newport, and Salmonella Poona
      in the gut of a free-living nematode, Caenorhabditis elegans, and transmission to
      progeny and uninfected nematodes.
AB  - A study was undertaken to determine the persistence of Escherichia coli O157:H7
      and salmonellae in the gut of a free-living nematode, Caenorhabditis elegans, as
      affected by temperature and relative humidity and to determine if infected worms
      transmit Salmonella enterica serotype Newport to progeny and uninfected worms.
      Worms were fed cells of a non-pathogenic strain of E. coli (OP50), E. coli
      O157:H7, S. enterica serotype Newport, and S. enterica serotype Poona, followed
      by incubating at 4, 20, or 37 degrees C for up to 5 days. Initial populations of
      ingested pathogens significantly increased by up to 2.93 log(10) cfu/worm within
      1 day at 20 degrees C on K agar and remained constant for an additional 4 days.
      When worms were placed on Bacto agar, populations of ingested pathogens remained
      constant at 4 degrees C, decreased significantly at 20 degrees C, and increased
      significantly at 37 degrees C within 3 days. Worms fed E. coli OP50 or S. Newport
      were incubated at 4 or 20 degrees C at relative humidities of 33%, 75%, or 98% to
      determine survival characteristics of ingested bacteria. Fewer cells of the
      pathogens survived incubation at 33% relative humidity compared to higher
      relative humidities. Populations of ingested E. coli OP50 and S. Newport
      decreased by up to 1.65 and 3.44 log(10) cfu/worm, respectively, in worms
      incubated at 20 degrees C and 33% relative humidity. Placement together on K agar
      of adult worms, labeled with green fluorescent protein (gfp) in the pharynx area,
      that had ingested gfp-labeled S. Newport and uninfected wild type worms resulted
      in transfer of the pathogen to gut of wild type worms. S. Newport was isolated
      from C. elegans two generations removed from exposure to the pathogen. Results of
      these studies show that C. elegans may serve as a temporary reservoir of
      foodborne pathogens, and could perhaps be a vector for contaminating preharvest
      fruits and vegetables, thus potentially increasing the risk of enteric infections
      associated with consumption of raw produce.

PMID- 15862885
TI  - Pesticides as a source of microbial contamination of salad vegetables.
AB  - Ten commercially available pesticides (insecticides, herbicides and fungicides),
      used during the production of vegetable produce, were examined as potential
      sources of microbial contaminants. As purchased, none of the pesticides showed
      the presence of viable microorganisms (< 5 CFU/ml). Using an agar plate diffusion
      assay, they did not inhibit a range of bacteria of spoilage and public health
      significance on vegetable produce. After reconstitution in sterile water to their
      recommended concentration, two of the pesticides supported the survival and
      growth of inoculated species of Pseudomonas, Salmonella and Escherichia coli.
      Listeria monocytogenes did not survive after inoculation into any of the
      pesticides. Pesticides were reconstituted in different sources of agricultural
      water (bore, dam and river) and examined for survival and growth of
      microorganisms naturally present in these waters. On storage at 30 degrees C for
      48 h, nine of the pesticides supported the growth of bacterial species present in
      these waters. Predominant species in the pesticide solutions, before and after
      storage, varied according to the source, but species of Pseudomonas,
      Acinetobacter and Aeromonas and various coliforms exhibited significant growth.
      Unless managed properly (reconstituted in potable water, and used without lengthy
      storage), pesticides could contribute to the microbial load of vegetable produce,
      thereby affecting their shelf-life and public health safety.

PMID- 15862886
TI  - Mitochondrial Ca2+ buffering in hypoglossal motoneurons from mouse.
AB  - A variety of studies demonstrated a crucial role of mitochondria for clearance of
      Ca2+ loads in motoneurons. However, previous reports rarely addressed the
      potential influence of cell dialysis during patch-clamp recordings or temperature
      on mitochondrial processes. We therefore developed a protocol allowing
      investigation of Ca2+ dynamics in "undisturbed" AM-ester loaded hypoglossal
      motoneurons in a slice preparation. By comparing our findings to previous
      results, we argue against a significant disturbance of mitochondrial buffering by
      cell dialysis. By varying bath temperatures between 19 and 32 degrees C, we show
      that temperature alters the rate of mitochondrial uptake but not the relative
      contribution to maintenance of Ca2+ homeostasis. The results further indicate
      that mitochondria in hypoglossal motoneurons participate in intracellular Ca2+
      regulation at concentrations much lower than has been generally observed for
      other neurons or neuroendocrine cells. Taken together, our findings further
      support the important role of mitochondria as regulators of Ca2+ homeostasis in
      motoneurons.

PMID- 15862887
TI  - Homotopic and heterotopic effects of endogenous analgesia in healthy volunteers.
AB  - Although research on DNIC has revealed the inhibitory effect occurring between
      two remote pain stimuli, the interrelation between two adjacent painful stimuli
      has not yet been characterized. In the present study, we used a sample of 40
      healthy volunteers to examine the effect of 30-s immersion of the fingers in
      water of 1 degree C, as a conditioning stimulus, on pain intensities produced by
      conditioned mechanical punctuate stimuli, applied both adjacent and contralateral
      to the cooled area. There was a significant decrease in mechanical pain
      intensities from 17.23+/-2.39 at baseline to 12.45+/-2.39 when stimulating
      immediately after the cold immersion at an adjacent site, and from 20.00+/-2.39
      to 15.08+/-2.39 at remote sites (F=20.02, p<0.0001). A significant positive
      correlation between the extent of pain reduction in the cooled and in the
      uncooled hand was found (r(s)=0.59, p=0.0001). The extent of pain reduction
      following cooling in the cooled and in the uncooled hand was also found to be
      similar for males and for females (p=0.63). It is concluded that under the
      conditions of this experiment, EA affects heterotopic and homotopic regions
      similarly and without gender differences.

PMID- 15862888
TI  - D-amphetamine enhances skilled reaching after ischemic cortical lesions in rats.
AB  - Unilateral sensorimotor cortical (SMC) lesions in rats impair reaching and
      grasping movements of the contralateral forelimb. These impairments can be
      improved using motor rehabilitative training on a skilled reaching task, but the
      training may be far from sufficient to return animals to pre-lesion levels of
      performance. Because D-amphetamine (AMPH) has been found to promote neuroplastic
      responses to injury and to be very beneficial when combined with some (but not
      all) types of rehabilitative training, we asked in this experiment whether it
      could improve the efficacy of rehabilitative training in skilled reaching. Ten to
      14 days after unilateral ischemic (endothelin-1 induced) lesions of the SMC,
      adult rats were given a 3-week regimen of AMPH (1mg/kg) coupled with daily
      rehabilitative training on a skilled reaching task, the single pellet retrieval
      task. AMPH treatment not only dramatically improved reaching performance compared
      with saline-injected controls, the AMPH treated rats surpassed pre-lesion levels
      of performance by the end of the rehabilitative training period. The greater
      performance in AMPH compared to saline-treated rats was still evident at 1 month,
      but not at 2 and 3 months, after the end of rehabilitative training. Thus, AMPH
      treatment can greatly enhance the efficacy of rehabilitative training on a
      skilled reaching task after unilateral SMC lesions, but alternate injection and
      training regimes may be needed to produce permanent improvements.

PMID- 15862889
TI  - The APOC3 SstI polymorphism is weakly associated with sporadic Alzheimer's
      disease in a Chinese population.
AB  - In order to clarify the relationship of apolipoprotein CIII (APOC3) polymorphism
      and sporadic Alzheimer's disease (AD) in Chinese, 165 sporadic AD patients and
      174 age-matched elderly individuals were genotyped for the APOC3 SstI and
      apolipoprotein E (APOE) HhaI polymorphisms. As the result, the APOC3 3017G allele
      was found to be associated with AD in APOE epsilon4 allele noncarriers
      (chi2=4.433, P=0.035), and the risk estimate of allele C versus G resulted in an
      OR of 1.56 (95% CI: 1.03-2.37), although in total no significant differences of
      allelic or genotypic frequencies between patients and controls were found.
      Assessment of interaction between APOE epsilon4 and APOC3 3017G status presented
      an adjusted odds ratio of 0.62 (95% CI: 0.37-1.03) with a borderline significant
      P-value (P=0.066). Therefore, we conclude that the rare APOC3 G allele may offer
      some protection against the development of sporadic AD in APOE epsilon4
      noncarriers in Chinese.

PMID- 15862890
TI  - Methylation of NMDA receptor NR2B gene as a function of age in the mouse brain.
AB  - We have previously reported that there is an up-regulation of the NR2B gene
      expression in the adult cortex and cultured fetal cortical neurons of mice
      following chronic ethanol treatment due to demethylation of cytosine residues in
      the NR2B gene CpG island. In the present study, we investigated the methylation
      pattern of the NR2B CpG island as a function of the mouse age by digesting the
      cortex genomic DNA with HpaII enzyme, amplifying the interested regions by
      performing PCR and detecting the methylated regions by Southern hybridization so
      as to determine whether age affects the methylation process. We observed
      demethylation of various regions of NR2B gene (5227-5567), (5647-6003), (6091
      6445), (6424-7024) of adult mouse cortex. Our results indicate that methylation
      of NR2B gene in the mouse brain is age-dependent phenomenon.

PMID- 15862891
TI  - Geldanamycin treatment reduces delayed CA1 damage in mouse hippocampal
      organotypic cultures subjected to oxygen glucose deprivation.
AB  - Our prior work demonstrated that geldanamycin (GA) reduced injury due to oxygen
      glucose deprivation (OGD) in primary astrocyte cultures. Using medium with an
      ionic composition similar to that observed during in vivo global ischemia, the
      selectivity and temporal profile of CA1 neuronal damage seen in vivo was mimicked
      with OGD in mouse hippocampal organotypic slice cultures. The present study
      tested the ability of GA to reduce delayed neuronal death in such cultures.
      Treating organotypic cultures with 100 nM GA for 24 h prior to OGD induced Hsp70
      and significantly reduced CA1 neuronal damage. Staining with ubiquitin to
      identify protein aggregates revealed reduced redistribution of ubiquitin,
      consistent with reduced protein aggregation likely due at least in part to
      induction of Hsp70 by GA.

PMID- 15862892
TI  - Ebselen prevents noise-induced excitotoxicity and temporary threshold shift.
AB  - This investigation tested the hypothesis that a noise-induced temporary threshold
      shift (TTS) can be attenuated by a peroxynitrite scavenger, ebselen (2-phenyl-1,2
      benzisoselenazol-3(2H)-one). Guinea pigs received an oral dose of the vehicle or
      10 mg/kg ebselen 1h before exposure to 115 dB SPL 4-kHz octave band noise for 3
      h. In controls, auditory brainstem response (ABR) thresholds increased by 25-45
      dB immediately after noise and returned to pre-exposure baseline thresholds 7
      days later. Ebselen eliminated this ABR threshold shift following noise exposure.
      In controls, swelling of the afferent dendrites beneath the inner hair cells was
      evident immediately after noise, whereas ebselen significantly reduced this
      pathology. These findings suggest that scavenging peroxynitrite can attenuate
      noise-induced excitotoxicity and, thereby, TTS.

PMID- 15862893
TI  - Difference in obesity phenotype between orexin-knockout mice and orexin neuron
      deficient mice with same genetic background and environmental conditions.
AB  - Orexins are a pair of neuropeptides expressed by a population of neurons located
      in the lateral hypothalamic area (LHA). Prepro-orexin- or orexin receptor type 2
      deficient animals exhibit a phenotype remarkably similar to the human sleep
      disorder, narcolepsy, which is characterized by sleep/wakefulness fragmentation.
      Human narcolepsy is known to be associated with metabolic abnormalities,
      including an increased frequency of obesity and non-insulin-dependent diabetes
      mellitus. Complex disruption of energy homeostasis in orexin neuron-deficient
      transgenic mice (orexin/ataxin-3 mice) is also manifested as late-onset obesity
      despite eating less. Here, we report that the development of obesity in orexin
      neuron-ablated narcoleptic mice is critically dependent on their genetic
      background and environmental factors, and the phenotype is different from that of
      prepro-orexin knockout mice even under the same genetic background and
      environmental factors, suggesting that factors that co-localize in orexin neurons
      might have important roles in the regulation of energy homeostasis. Our
      observation also suggests that the obesity observed in orexin neuron-deficient
      narcolepsy is dependent on the genetic background and environmental factors.

PMID- 15862894
TI  - Kanamycin ototoxicity in glutamate transporter knockout mice.
AB  - Glutamate-aspartate transporter (GLAST), a powerful glutamate uptake system,
      removes released glutamate from the synaptic cleft and facilitates the re-use of
      glutamate as a neurotransmitter recycling system. Aminoglycoside-induced hearing
      loss is mediated via a glutamate excitotoxic process. We investigated the effect
      of aminoglycoside ototoxicity in GLAST knockout mice using the recorded auditory
      brainstem response (ABR) and number of hair cells in the cochlea. Kanamycin (100
      mg/mL) was injected directly into the posterior semicircular canal of mice.
      Before the kanamycin treatment, there was no difference in the ABR threshold
      average between the wild-type and knockout mice. Kanamycin injection aggravated
      the ABR threshold in the GLAST knockout mice compared with the wild-type mice,
      and the IHC degeneration was more severe in the GLAST knockout mice. These
      findings suggest that GLAST plays an important role in preventing the
      degeneration of inner hair cells in aminoglycoside ototoxicity.

PMID- 15862895
TI  - Effect of L-type calcium channel antagonists on spermine-induced CNS excitation
      in vivo.
AB  - The ability of nitrendipine, nisoldipine, verapamil and gabapentin to inhibit the
      development of CNS excitation induced by spermine was assessed in mice. Injection
      of an excitotoxic dose of spermine (100 microg, i.c.v.) in mice results in
      worsening tremor that culminates in the development of a fatal tonic convulsion
      within 8 h of spermine administration. The dihydropyridines, nitrendipine and
      nisoldipine, which are L-type calcium channel antagonists acting at the alpha1
      subunit, inhibited the development of spermine-induced effects. Verapamil, which
      also acts at the alpha1 subunit of the L-type calcium channel, also inhibited the
      development of spermine-induced CNS excitation. Gabapentin, a postulated L-type
      calcium channel antagonist interacting at the alpha2delta subunit, did not
      inhibit the development of spermine-induced effects. These results show that
      antagonists of the alpha1 subunit of L-type calcium channels can effectively
      inhibit the effects of spermine in vivo. This may highlight the importance of L
      type calcium channels in spermine action.

PMID- 15862896
TI  - Degeneration of dopaminergic neurons in the substantia nigra of zitter mutant rat
      and protection by chronic intake of Vitamin E.
AB  - Dopaminergic cell death in the ventral and dorsal tiers of substantia nigra pars
      copmacta (SNc) and their prevention by anti-oxidant diet was
      immunohistochemically studied in the zitter mutant rats, which are characterized
      by abnormal metabolism of superoxide. Similar to previous reports, the number of
      SNc neurons in Nissl-stained section decreased with age. Tyrosine hydroxylase
      (TH) immunohistochemistry demonstrated that the dopaminergic neurons in the
      ventral tier of SNc degenerated early, whereas the dorsal tier gradually
      degenerated with age. Thus, the ventral tier dopaminergic neurons are affected
      first, but the dorsal tier neurons do become impact by the zi/zi mutation.
      Following 9-month period after weaning, zitter rats supplemented with 500 mg D,L
      alpha-tocophenol (VE(+))/kg diet exhibited a significant increased of surviving
      TH-immunoreactive neurons in both the tiers of SNc as compared with the zi/zi
      rats with control and VE(-) diets. These results suggest that VE supplement may
      slow the dopaminergic cell loss in zitter mutant rat, and further support that
      degeneration of the dopaminergic neurons in this mutant rat is caused by oxidant
      stress. Thus, the zitter rat may represent a good model for studying the
      dopaminergic cell death by superoxide species.

PMID- 15862897
TI  - Homozygous partial genomic triplication of the parkin gene in early-onset
      parkinsonism.
AB  - Autosomal recessive mutations in the parkin gene are the predominant cause of
      familial, early-onset parkinsonism; missense mutations involving one or a few
      nucleotides, exonic deletions and duplications have been described. Here we
      report a family with two affected brothers. Direct sequencing of parkin did not
      detect mutations, but semi-quantitative analysis identified a novel exonic
      rearrangement of exons 2-4. Both patients were homozygous for unique genomic
      triplications of the parkin gene.

PMID- 15862898
TI  - ADAM23 methylation and expression analysis in brain tumors.
AB  - The ADAMs comprises a family of cell surface proteins with putative roles in cell
      cell and/or cell-matrix interactions and in protease activities. In this work, we
      have examined the expression level and the methylation status of the 5' upstream
      region of the adhesion molecule ADAM23 in two brain tumor cell lines (A172 and
      T98G) as well as in three primary brain tumors (one grade II astrocytoma and two
      meningiomas) and 15 glioblastoma xenografts. Using bisulfite sequencing we
      verified that the percentage of methylated dinucleotides is higher in T98G when
      compared to A172 and that methylation significantly correlates with ADAM23 mRNA
      and protein expression. However, we were unable to detect methylation and down
      regulation of the ADAM23 gene in brain tumors. Together, these results indicate
      that ADAM23 down-regulation by methylation in brain tumors is a rare event and it
      may help explain why brain tumor metastases are rarely found elsewhere in the
      body.

PMID- 15862899
TI  - Muscle coordination changes during intermittent cycling sprints.
AB  - Maximal muscle power is reported to decrease during explosive cyclical exercises
      owing to metabolic disturbances, muscle damage, and adjustments in the efferent
      neural command. The aim of the present study was to analyze the influence of
      inter-muscle coordination in fatigue occurrence during 10 intermittent 6-s
      cycling sprints, with 30-s recovery through electromyographic activity (EMG).
      Results showed a decrease in peak power output with sprint repetitions (sprint 1
      versus sprint 10: -11%, P<0.01) without any significant modifications in the
      integrated EMG. The timing between the knee extensor and the flexor EMG
      activation onsets was reduced in sprint 10 (sprint 1 versus sprint 10: -90.2 ms,
      P<0.05), owing to an earlier antagonist activation with fatigue occurrence. In
      conclusion, the maximal power output, developed during intermittent cycling
      sprints of short duration, decreased possibly due to the inability of muscles to
      maintain maximal force. This reduction in maximal power output occurred in
      parallel to changes in the muscle coordination pattern after fatigue.

PMID- 15862900
TI  - The cannabinoid antagonist SR141716A facilitates memory acquisition and
      consolidation in the mouse elevated T-maze.
AB  - Delta9-THC and synthetic cannabinoids produce memory impairment in humans as well
      as in laboratory animals. The high concentration of cannabinoid CB1 receptors and
      the presence of endocannabinoids in the hippocampus suggest that a cannabinoid
      neurochemical system may play a role in learning and memory processes. Thus, the
      objective of the present work was to study the effect of the cannabinoid
      antagonist SR141716A (SR) on memory acquisition, consolidation and retrieval in a
      recently developed elevated T-maze (ETM) model of anxiety and memory. In
      addition, we investigated whether pre-training SR administration was capable of
      reversing scopolamine-induced memory impairment. Adult male mice were exposed to
      the closed arm as many times as necessary for the animals to reach the avoidance
      criterion of remaining in the closed arm for 300 s; they were then tested
      (exposed to the closed arm) 24 h and 7 days after the training. SR (0.5, 1.0 or
      2.0 mg/kg) was administered i.p. 20 min before the training, immediately after
      training or 20 min before the test in the mice. The elevated plus-maze (EPM) was
      used to investigate a possible influence of SR on locomotion and on the anxiety
      related behavior. SR provoked memory improvement, which was observed when the
      drug was administered before (effect on memory acquisition/consolidation) or
      immediately after the training (effect on memory consolidation), but not when the
      drug was administered before the test (effect on memory retrieval). Also, SR
      administration reversed scopolamine-induced amnesia. These effects were observed
      in the absence of changes in locomotion or anxiety levels. Our results
      demonstrate that the blockade of cannabinoid receptors may improve memory
      acquisition and consolidation in the ETM model.

PMID- 15862901
TI  - Reticulo-collicular projections: a neuronal tracing study in the rat.
AB  - Neuroanatomical tract-tracing methods were used to study the topography of the
      reticulocollicular projections. Injections of gold-HRP or BDA tracers into the
      medial and/or central portions of the superior colliculus resulted in labelled
      neurones mainly in the medial reticular formation, whereas injections into the
      lateral portion of the superior colliculus showed labelling in the medial and
      lateral reticular formation. When tracer was injected into the lateral portion of
      the caudal superior colliculus, extensive lateral labelling was observed in the
      contralateral parvocellular reticular nucleus and the contralateral dorsal
      medullary reticular nucleus, two areas involved in reflex blinking. The present
      study shows that these reticular areas project to the lateral superior
      colliculus, which is known to be involved in the coordination of eye and eyelid
      movements.

PMID- 15862902
TI  - Altered expression patterns of metabotropic glutamate receptors in diffuse brain
      injury.
AB  - The metabotropic glutamate receptors (mGluRs), as one of the newly found
      glutamate receptors, play an important role in the physiological processes of the
      central nervous system. The authors examined the changes of expression patterns
      of mGluRs after diffuse brain injuries (DBI) in rats. DBI was produced by
      Marmarou's methods. The mRNA expression of mGluRs was detected by hybridization
      in situ at different time points after brain injuries. Compared with normal
      control and sham-operated control, the animals with DBI showed a significantly
      increased expression of group I and group III mGluRs (except mGluR6, P<0.05). The
      increased peak of group I appeared at 24 h after injuries and group III at 6 h
      after injuries. While, group II mGluRs decreased after DBI (P<0.05) and the
      lowest point occurred at 48 h after DBI. The difference of time sequence of the
      expression alterations between group I and group III mGluRs may reflect a self
      protection first mechanism of the damaged neurons. It may provide new insight for
      the development of new pharmaceuticals in the treatment of DBI.

PMID- 15862903
TI  - Oxidized galectin-1 advances the functional recovery after peripheral nerve
      injury.
AB  - Oxidized galectin-1 has been shown to promote axonal regeneration from transected
      nerve sites in an in vitro dorsal root ganglion (DRG) explant model as well as in
      in vivo peripheral nerve axotomy models. The present study provides evidence that
      oxidized galectin-1 advances the restoration of nerve function after peripheral
      nerve injury. The sciatic nerve of adult rats was transected and the distal nerve
      was frozen after being sutured into a proximal site with four epineurial
      stitches. An osmotic pump delivered oxidized galectin-1 peripherally to the
      surgical site. Functional recovery was assessed by measurement of the degree of
      toe spread of the hind paw for 3 months after the sciatic nerve lesion. The
      recovery curves of toe spread in the test group showed a statistically
      significant improvement of functional recovery after day 21 by the application of
      oxidized recombinant human galectin-1 (rhGAL-1/Ox) compared to the control group.
      This functional recovery was supported by histological analysis performed by
      light microscopic examination. The regenerating myelinated fibers at the site 21
      mm distal to the nerve-transected site were quantitatively examined at 100 days
      after the operation. The frequency distribution of myelinated fiber diameters
      showed that exogenous rhGAL-1/Ox increased the number and diameter of
      regenerating myelinated fibers; the number of medium-sized (6-11 microm in
      diameter) fibers increased significantly (P<0.05). These results indicate that
      oxidized galectin-1 promotes the restoration of nerve function after peripheral
      nerve injury. Thus, rhGAL-1/Ox may be a factor for functional restoration of
      injured peripheral nerves.

PMID- 15862904
TI  - Olfactory stimulation with scent of grapefruit oil affects autonomic nerves,
      lipolysis and appetite in rats.
AB  - In a previous study, we found that olfactory stimulation with scent of grapefruit
      oil (SGFO) excites the sympathetic nerve innervating the white adipose tissue in
      rats. Here we further examined the effects of SGFO in rats and observed that
      olfactory stimulation with SGFO excited the sympathetic nerves innervating the
      brown adipose tissue and adrenal gland and inhibited the parasympathetic gastric
      nerve. Local anesthesia of the nasal mucosa with xylocaine or anosmic treatment
      using ZnSO4 eliminated the autonomic changes caused by SGFO. Moreover,
      stimulation with SGFO elevated the plasma glycerol level, and treatment with
      either ZnSO4 or an intraperitoneal injection of diphenhydramine, a histamine H1
      receptor-antagonist, abolished the glycerol elevation by SGFO. Furthermore, a 15
      min exposure to SGFO three times a week reduced food intake and body weight.
      Finally, limonene, a component of grapefruit oil, induced responses similar to
      those caused by SGFO, and diphenhydramine eliminated the glycerol response to
      limonene. Thus, the scent of grapefruit oil, and particularly its primary
      component limonene, affects autonomic nerves, enhances lipolysis through a
      histaminergic response, and reduces appetite and body weight.

PMID- 15862905
TI  - Divergent glial fibrillary acidic protein and its mRNA in the activated
      supraoptic nucleus.
AB  - Previous studies have shown decreased immunoreactive glial fibrillary acidic
      protein (GFAP) in the supraoptic nucleus (SON) when magnocellular neuroendocrine
      cells (MNCs) are activated by lactation or dehydration. This is thought to
      underlie structural plasticity of glial processes that occurs during these times.
      Here, we investigated how this apparent reduction in protein relates to GFAP mRNA
      expression in the dehydrated rat as visualized by in situ hybridization.
      Densitometry of silver grains in the SON revealed low levels of mRNA expression
      in control, 2-day dehydrated and 21-day rehydrated (R21) animals. Conversely, the
      SON from 7-day dehydrated (D7) subjects displayed significantly more silver
      grains. Thus, the pattern of GFAP mRNA expression is the inverse of what we
      previously observed for GFAP immunoreactivity in tissue sections of the SON. No
      differences in mRNA levels due to hydration state were seen in the lateral
      hypothalamic area, suggesting that increases in GFAP mRNA at D7 were specifically
      related to MNC activation. These data indicate a divergence in GFAP mRNA and
      protein expression in the SON.

PMID- 15862906
TI  - The effect of prenatal morphine exposure on memory consolidation in the chick.
AB  - The central nervous system exhibits remarkable plasticity in early life and can
      be altered significantly by prenatal morphine exposure. Previous studies show
      that prenatal morphine exposure may alter the capacity for learning and memory in
      post-partum chicks. The one-trial passive avoidance learning paradigm with 1-day
      old chicks is an excellent model to study several mechanisms of memory formation,
      including STM, ITM, and LTM. The following represents our investigation of the
      effect of prenatal morphine exposure on learning and memory deficits in the
      chick. In these experiments, morphine was injected into the airspace of eggs (20
      mg/kg) and the one-trial passive avoidance learning paradigm was used to test the
      effect of prenatal morphine exposure on memory consolidation. The data suggest
      that chicks injected with morphine daily from E12 to E16 had significantly
      impaired long-term memory at 120 min after training (p<0.001) but not
      intermediate-term memory at 30 min after training.

PMID- 15862907
TI  - The intralimb coordination of the flexor reflex response is altered in chronic
      human spinal cord injury.
AB  - The current study compared the intralimb coordination of flexor reflex responses
      in spinal intact and complete chronic spinal cord injured (SCI) individuals.
      Noxious electrocutaneous stimulation was applied at the apex of the medial arch
      of the foot (50 mA, 500 Hz, 1 ms pulse width, 20 ms) in 21 complete chronic SCI
      and 19 spinal intact volunteers and the flexor reflex response was quantified by
      measuring the isometric joint torques at the ankle, knee and hip. The results
      showed that SCI individuals had significantly smaller peak knee and hip joint
      flexion torques, often exhibited a net knee extension torque, and produced a much
      smaller hip joint flexion torque during the flexor reflex response in contrast to
      the spinal intact individuals. The latency of the reflex response, measured from
      the tibialis anterior electromyogram, was comparable in both test populations.
      These findings indicate that the intralimb coordination of the flexor reflex
      response of chronic complete SCI individuals is altered, possibly reflecting a
      functional reorganization of the flexion pathways of the spinal cord.

PMID- 15862908
TI  - Estrogen suppresses the stress response of prolactin-releasing peptide-producing
      cells.
AB  - Prolactin-releasing peptide (PrRP) is known to be produced in A1/A2 noradrenergic
      neurons and to mediate the stress response. Our preliminary experiment showed
      that PrRP neurons in the A2 region differed between males and females in terms of
      c-Fos expression. In addition it has been reported that estrogen receptor alpha
      is detectable in A2 PrRP neurons. Therefore, we speculated that the stress
      response of PrRP neurons is modified by estrogen. We, therefore, examined c-Fos
      expression in A2 PrRP neurons during the estrous cycle and found that c-Fos
      accumulation in PrRP neurons was significantly decreased in estrus compared with
      in proestrus, metestrus and diestrus. This suggests that estrogen suppresses the
      activation of PrRP neurons. We thus administered diethylstilbestrol (DES) to
      ovariectomized rats and then added restraint stress. The data clearly showed that
      PrRP cells in DES-administered rats significantly suppressed c-Fos accumulation
      induced by stress.

PMID- 15862909
TI  - Noradrenergic receptor mRNA expression in adult rat superficial dorsal horn and
      dorsal root ganglion neurons.
AB  - Noradrenaline (NAdr) has well documented analgesic actions at the level of the
      spinal cord. Released from bulbospinal projections onto superficial dorsal horn
      (SDH) neurons, NAdr modulates the excitability of these neurons through the
      activation of alpha1, alpha2 or beta adrenoceptors. This study utilised in situ
      hybridisation to determine the specific expression of adrenoceptors within adult
      rat lumbar SDH and dorsal root ganglion (DRG) neurons, and reports the presence
      of alpha1A, alpha1B, alpha2B, beta1 and beta2 adrenoceptor mRNA within SDH
      neurons, and the presence of alpha1A, alpha1B and alpha2C adrenoceptor mRNA
      within DRG neurons. The present study provides an insight into the modulation of
      sensory processing at the level of the spinal cord following adrenoceptor
      activation.

PMID- 15862910
TI  - Human umbilical cord blood cells express neurotrophic factors.
AB  - Freshly isolated or culture-expanded human umbilical cord blood mononuclear cells
      (CBMNCs) have been known to express neural phenotypes in vitro and to
      differentiate into neural cells and improve neurological function recovery after
      being administrated into rodent models of neurological diseases. However, the
      mechanism of action remains unclear. The present study observed that CBMNCs
      expressed higher level mRNAs of several neurotrophic factors than adult
      peripheral blood mononuclear cells (PBMCs). In addition, a significantly increase
      in the levels of brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5
      (NT4/5) was found in culture supernatants of CBMNCs compared to that of PBMNCs.
      These findings indicate that CBMNCs express several neurotrophic factors and
      suggest that the neurotrophic factors secreted by CBMNCs may be responsible for
      amelioration of central nervous system deficits in animal models after CBMNC
      administration.

PMID- 15862911
TI  - Altered motor cortex excitability in tinnitus patients: a hint at crossmodal
      plasticity.
AB  - Idiopathic tinnitus is a frequent and often debilitating auditory phantom
      perception of largely unknown pathological conditions. In electrophysiological
      and functional neuroimaging studies, affected subjects have shown excessive
      spontaneous activity in the central auditory system. To further investigate the
      underlying central nervous component, we assessed motor cortex excitability in 19
      patients with chronic tinnitus by means of transcranial magnetic stimulation
      (TMS). When results were compared with data from 19 healthy controls matched for
      age and sex, we found significantly enhanced intracortical facilitation in
      tinnitus patients. These findings parallel excitability changes after limb
      amputation and experimental deafferentation. Our results give further support to
      crossmodal interactions involving neuroplastic changes in some forms of tinnitus
      and may help to better understand mechanisms of maladaptive cortical
      reorganisation involved in phantom perceptions.

PMID- 15862912
TI  - Calcium dependence of axotomized sensory neurons excitability.
AB  - Hyperexcitability of axotomized dorsal root ganglion neurons is thought to play a
      role in neuropathic pain. Numerous changes in ionic channels expression or
      current amplitude are reported after an axotomy, but to date no direct
      correlation between excitability of axotomized sensory neurons and ionic channels
      alteration has been provided. Following sciatic nerve injury, we examined, under
      whole-cell patch clamp recording, the effects of calcium homeostasis on the
      electrical activity of axotomized medium-sized sensory neurons isolated from
      lumbar dorsal root ganglia of adult mice. Axotomy induced an increase in
      excitability of medium sensory neurons among which 25% develop a propensity to
      fire repetitively. The condition necessary to get burst discharge in axotomized
      neurons was the presence of a high intracellular Ca2+ buffer concentration. The
      main effect was to amplify the increase in threshold current and apparent input
      resistance induced by axotomy. These data supply evidence for a role of Ca2+
      dependent mechanisms in the control of excitability of axotomized sensory
      neurons.

PMID- 15862913
TI  - Involvement of the laterodorsal tegmental nucleus in the locomotor response to
      repeated nicotine administration.
AB  - The locomotor altering properties of nicotine depend on activation of nicotinic
      acetylcholine receptors in the ventral tegmental area (VTA). The laterodorsal
      tegmental nucleus (LDTg) provides a significant proportion of the cholinergic
      innervation of the VTA. We tested the hypothesis that the locomotor effects of
      nicotine depend on the functional integrity of the LDTg. The spontaneous
      locomotor activity of LDTg and sham-lesioned control rats was measured over seven
      sessions, after which we examined the effects of repeated injections of nicotine
      in a day on-day off design, giving injections of saline on the nicotine-off days.
      Spontaneous locomotor activity was significantly lower in LDTg lesioned compared
      to control rats. LDTg lesions also blunted the effects of nicotine: control rats
      showed an initial locomotor depression after nicotine, but on repeated testing
      showed a progressive increase in the amount of locomotion in response to drug
      challenge. LDTg lesioned rats showed no differences in responding to nicotine
      compared to saline. These data show that the functional integrity of the LDTg is
      required in order to show normal locomotor response to nicotine. One explanation
      for this is that loss of the LDTg affects synaptic activity in the VTA.

PMID- 15862914
TI  - A yellow fluorescent protein-based assay for high-throughput screening of glycine
      and GABAA receptor chloride channels.
AB  - There is a significant clinical need to identify novel ligands with high
      selectivity and potency for GABA(A), GABA(C) and glycine receptor Cl- channels.
      Two recently developed, yellow fluorescent protein variants (YFP-I152L and YFP
      V163S) are highly sensitive to quench by small anions and are thus suited to
      reporting anionic influx into cells. The aim of this study was to establish the
      optimal conditions for using these constructs for high-throughput screening of
      GABA(A), GABA(C) and glycine receptors transiently expressed in HEK293 cells. We
      found that a 70% fluorescence reduction was achieved by quenching YFP-I152L with
      a 10 s influx of I- ions, driven by an external I- concentration of at least 50
      mM. The fluorescence quench was rapid, with a mean time constant of 3 s. These
      responses were similar for all anion receptor types studied. We also show the
      assay is sufficiently sensitive to measure agonist and antagonist concentration
      responses using either imaging- or photomultiplier-based detection systems. The
      robustness, sensitivity and low cost of this assay render it suited for high
      throughput screening of transiently expressed anionic ligand-gated channels.

PMID- 15862915
TI  - A response to Granqvist et al. "Sensed presence and mystical experiences are
      predicted by suggestibility, not by the application of transcranial weak magnetic
      fields".

PMID- 15862917
TI  - Alpha rhythms in mild dements during visual delayed choice reaction time tasks: a
      MEG study.
AB  - Can simple delayed response tasks affect latency and amplitude of
      magnetoencephalographic midline alpha rhythms (6-12 Hz) in early dementia? We
      recruited 15 mild Alzheimer's disease (AD) and 10 vascular dementia (VaD)
      patients (paired mini mental state exam of 17-24). The control groups comprised
      18 young and 22 elderly normal subjects. In the first task, a simple "cue"
      stimulus (one bit) was memorized along a brief delay period (3.5-5.5s) up to a
      "go" stimulus triggering (right or left) button press. In the second task, the
      "cue" stimulus remained available along the delay period. Event-related reduction
      in power of the alpha rhythms indexed the cortical activation (event-related
      desynchronization, ERD) for the trials associated with correct behavioral
      responses. Behavioral performances to both tasks were lower in the AD and VaD
      patients than in the normal subjects. In particular, just four AD and five VaD
      patients executed a sufficient amount of correct responses for the alpha ERD
      analysis, so they were included in a unique group. In both tasks, the alpha ERD
      peak was later in latency in the demented and normal elderly subjects than in the
      normal young subjects. Furthermore, the alpha ERD peak was stronger in amplitude
      in the demented patients than in the normal subjects. These results suggest that
      simple delayed response tasks during physiological recordings are quite difficult
      for patients even at an early dementia stage. Such difficulty may induce the
      abnormal amount of the related cortical activation in dementia as revealed by the
      alpha ERD.

PMID- 15862918
TI  - Enhanced neurogenesis during trimethyltin-induced neurodegeneration in the
      hippocampus of the adult rat.
AB  - The occurrence of neurogenesis in the hippocampus of the adult rat during
      trimethyltin (TMT)-induced neurodegeneration was investigated using
      bromodeoxyuridine (BrdU). Fifteen days after TMT intoxication, BrdU-labeled cells
      were significantly more numerous in the hippocampus of treated animals, gradually
      decreasing towards the control value 21 days after intoxication in the dentate
      gyrus (DG), while in the CA3/hilus region BrdU-labeled cells were still more
      numerous in TMT-treated rats. In order to investigate the fate of newly-generated
      cells double labeling experiments using neuronal or glial markers were performed.
      Colocalization of the neuronal marker NeuN was detected in many BrdU-positive
      cells in the DG, while in the CA3/hilus region no colocalization of NeuN and BrdU
      could be observed. No colocalization of BrdU and the astroglial marker GFAP or
      the microglial marker OX-42 was detected either in the DG and or in the CA3/hilus
      region. The results indicate an enhancement of endogenous neurogenesis in the
      hippocampus during TMT-induced neurodegeneration, with the development of a
      subpopulation of regenerated cells into neurons in the DG, while in the CA3/hilus
      region the population of newly-generated cells should be regarded as
      undifferentiated.

PMID- 15862919
TI  - Alterations of prenatal morphine exposure in mu-opioid receptor density in
      hypothalamic nuclei associated with sexual behavior.
AB  - Our previous work demonstrated that prenatal morphine exposure twice daily during
      gestational days 11-18 differentially alters male and female sexual behavior. One
      possible explanation may be that prenatal morphine exposure alters the sexual
      behavior via alterations of mu-opioid receptors in brain regions involved in
      reproductive function and behavior, including the ventromedial nucleus of the
      hypothalamus (VMH), arcuate nucleus (ARC), and medial preoptic area (mPOA). In
      experiment 1, mu-opioid receptor density was analyzed in three groups of adult
      male rats: gonadally intact, gonadectomized (GNX), and GNX and testosterone
      17beta-propionate-treated (TP). In experiment 2, mu-opioid receptor density was
      analyzed in four groups of adult female rats: ovariectomized (OVX), OVX and
      estradiol benzoate-treated (EB), OVX and progesterone-treated (P), and OVX and EB
      and P-treated (EB+P). Experiment 1 demonstrated that prenatal morphine exposure
      lowered the mu-opioid receptor density in the mPOA of adult, gonadally intact and
      in TP males, while this difference was not apparent in GNX male rats. Experiment
      2 demonstrated that prenatal morphine exposure increased mu-opioid receptor
      density in OVX females, while decreasing it in EB females in the VMH. When
      compared to our previous sexual behavior data, the present results demonstrate
      that at least some changes in sexual behavior of adult male and female rats
      prenatally exposed to morphine may be related to alterations in mu-opioid
      receptors in brain regions controlling sexual behavior.

PMID- 15862920
TI  - The effect of exercise and nettle supplementation on oxidative stress markers in
      the rat brain.
AB  - Chronic swimming training and phytotherapeutic supplementation are assumed to
      alleviate oxidative damage, and support cell survival in the brain. The effect of
      forced, chronic swimming training, and enriched lab chow containing 1% (w/w)
      dried nettle (Urtica dioica) leaf were investigated for oxidative stress,
      inflammation and neurotrophic markers in Wistar rat brains. The rats were divided
      into groups subjected to swimming training (6 weeks) or to nettle supplementation
      (8 weeks) or to a combination of these two treatments. The level of oxidative
      stress was measured by electron spin resonance (EPR), and by the concentration of
      carbonylated proteins. Nettle supplementation resulted in a decreased
      concentration of free radicals in both cerebellum and frontal lobe. Swimming,
      however, did not influence significantly the oxidative damage nor was it
      reflected in the carbonyl content. The protein content of nerve growth factor
      (NGF), and brain-derived neurotrophic factors (BDNF) was evaluated by E-Max
      ImmunoAssay in the cerebellum. No changes occurred either with exercise or nettle
      diet treatments. On the other hand, nuclear factor kappa B (NF-kappaB) binding
      activity to DNA increased with the combined effect of swimming training and
      nettle diet, while the activator protein1 (AP-1) DNA binding activity showed a
      more profound elevation in the nettle treated animals. The amount of c-Jun
      decreased by swimming training. In conclusion, the results suggest that both
      exercise and nettle influenced physiological brain functions. Nettle
      supplementation reduces the free radical concentration and increases the DNA
      binding of AP-1 in the brain. Nettle was found to be an effective antioxidant and
      possible antiapoptotic supplement promoting cell survival in the brain. Exercise,
      as a downregulator of c-Jun and in combined group as an upregulator of NF-kappaB,
      may play also a role in antiapoptotic processes, which is important after brain
      injury.

PMID- 15862922
TI  - Relational memory for object identity and spatial location in rats with lesions
      of perirhinal cortex, amygdala and hippocampus.
AB  - Previous studies dissociate medial temporal lobe regions using non-relational
      object versus relational spatial tasks. We compared a relational object identity
      task to the commonly used, relational spatial Morris water task. Lesions of
      perirhinal cortex, amygdala and hippocampus led to impaired performance on only
      the relational object preference task. Rats with perirhinal cortex and amygdala
      lesions performed normally on the Morris water task, but showed reduced
      perseveration in the correct quadrant on the probe trial. Rats with hippocampal
      damage were impaired on all measures of the Morris water task. Our findings
      demonstrate that perirhinal and amygdala damage creates impairments for
      relational tasks that rely on information processed by these structures (object
      identity and stimulus valence, respectively). In addition, these structures
      contribute non-essentially to performance of relational spatial tasks. The
      hippocampus is critical for all tasks that require the use of relational
      representations, regardless of whether the disambiguating information is provided
      by object identity or spatial arrangements. The current pattern of results
      suggests that the previous object-spatial dissociations among medial temporal
      lobe regions may be due to the relational nature of the spatial tasks versus the
      non-relational nature of the object tasks. Further, they illustrate that discrete
      dissociations among different types of processing may be an oversimplification.

PMID- 15862921
TI  - Erdosteine ameliorates PTZ-induced oxidative stress in mice seizure model.
AB  - The role of oxygen-derived free radicals has been suggested in genesis of
      epilepsy and in the post seizure neuronal death. The aim of this study was to
      investigate whether erdosteine has a preventive effect against epilepsy and
      postepileptic oxidative stress. The mice (n=27) were divided into three groups:
      (i) PTZ-induced-epilepsy group (n=9); (ii) PTZ-induced-epilepsy+erdosteine group
      (n=9); (iii) control group (n=9). The animals were observed for a period of 30
      min for latency to first seizure onset, total seizure duration, the number of
      seizure episodes. Then they were sacrificed and the brains were quickly removed,
      and frozen for biochemical analysis. Malondialdehyde (MDA), nitric oxide (NO),
      superoxide dismutase (SOD) and xanthine oxidase (XO) activities were carried out
      in the brain tissue. The latent period between PTZ induction and seizure are
      longer in the PTZ+erdosteine group than in PTZ-induced-epilepsy group (P<0.05).
      Biochemical analyses of brain tissue, revealed a significant increase in the MDA,
      XO and NO levels in the PTZ group according to erdosteine group. SOD level did
      not change in this group. While MDA and XO levels are significantly lower, SOD
      level is significantly higher in the PTZ+erdosteine group compared to PTZ and
      control groups (P<0.01). The present study demonstrated that erdosteine treatment
      both may increase latent interval between seizures and may decrease oxidative
      stress, thus may ameliorate neuronal death in brain during seizures. It may be
      used as an adjunct therapy in epilepsy.

PMID- 15862923
TI  - Circadian control during the day and night: Role of neuropeptide Y Y5 receptors
      in the suprachiasmatic nucleus.
AB  - Circadian rhythms are reset by light during the night or by nonphotic stimuli
      during the day. Neuropeptide Y (NPY), which appears to mediate at least some
      nonphotic phase shifts by its actions in the suprachiasmatic nucleus (SCN),
      induces phase advances during the day and inhibits light-induced phase advances
      during the night. In this study, we used a highly selective Y5-like agonist to
      test whether activation of NPY Y5 receptors is sufficient to mimic NPY during the
      day and late night in Syrian hamsters. We also tested whether NPY in the early
      night reduces light-induced phase delays in a dose-dependent manner.
      Microinjection of a selective Y5 receptor agonist, (Ala(31), Aib(32))-NPY, into
      the SCN significantly inhibited light-induced phase advances during the late
      night, but did not induce phase advances during the day. In addition,
      concentrations of NPY ranging from 0.23 to 23 mM did not attenuate light-induced
      phase delays in the early night. These results suggest that activation of Y5-like
      receptors is sufficient to inhibit light-induced phase advances during the late
      night but is not sufficient to induce phase advances during the day. Furthermore,
      this study provided no evidence that NPY can inhibit light-induced phase shifts
      early in the night.

PMID- 15862924
TI  - Release of arginine, glutamate and glutamine in the hippocampus of freely moving
      rats: Involvement of nitric oxide.
AB  - Using in vivo microdialysis, we have monitored the release of three amino acids
      (arginine, glutamate and glutamine) in the hippocampus of freely moving rats in
      response to various drugs. In response to N-methyl-d-aspartate (NMDA) infusion,
      extracellular glutamate was increased, glutamine was decreased and arginine
      remained unchanged. By contrast, alpha-amino-3-hydroxy-5-methyl-4
      isoxazoleproprionic acid (AMPA) elicited an increase in arginine release but had
      no effect on either glutamate or glutamine. When S-nitroso-N-acetylpenicillamine
      (SNAP), a nitric oxide (NO) donor, was infused into the hippocampus, an increase
      in glutamate, a decrease in glutamine and no change in arginine were recorded.
      The effect of SNAP on extracellular glutamine levels was reversed by prior
      infusion of the guanylate cyclase inhibitor oxadiazolo[4,3-alpha]quinoxalin-1-one
      (ODQ), however its effect on glutamate release was unchanged. Interestingly, SNAP
      was found to promote the release of arginine in the presence of ODQ. We also
      assessed the effect of two nitric oxide synthase inhibitors, N-nitro-l-arginine
      methylester (l-NAME) and 7-nitroindazole (7-NI), on the release of these amino
      acids. l-NAME was found to increase arginine and glutamate levels but decrease
      those of glutamine. In contrast, 7-NI reduced the release of all three amino
      acids. The results presented here confirm some but not all of the findings
      previously obtained using in vitro preparations. In addition, they suggest that
      complex relationships exist between the release of these amino acids, and that
      endogenous NO plays an important role in regulating their release.

PMID- 15862925
TI  - Pleiotrophin gene transcription in the rat nucleus accumbens is stimulated by an
      acute dose of amphetamine.
AB  - Pleiotrophin (PTN) is a heparin-binding protein with diverse functions. For
      example, it stimulates neurite outgrowth, mitogenesis, repair and
      differentiation, effects that are similar to those of the neurotrophins. The
      neurotrophins have, in recent years, been implicated as mediators of structural
      plasticity, suggested to underlie the development of behavioural sensitisation to
      many drugs of abuse. Since NMDA receptor antagonists inhibit the underlying
      morphological changes, the mechanisms are thought to be highly dependent on the
      activation of the NMDA subtype of glutamate receptors. To investigate if PTN has
      a possible role in structural plasticity, its responsiveness to an acute dose of
      amphetamine was studied. Amphetamine is a well-characterised inducer of
      sensitisation. A group of rats was systemically treated with amphetamine (10
      mg/kg) and the effect on the PTN gene transcription was studied 4 h later. A
      separate group of rats was pretreated with the NMDA receptor antagonist MK-801
      (0.25 mg/kg) 30 min prior to the administration of amphetamine. Northern blot
      analysis revealed a significant increase of the PTN transcript after the
      administration of amphetamine. However, MK-801 pretreatment did not block this
      effect; in contrast, it further increased PTN mRNA levels. As the response to the
      two drugs resembles the one earlier reported on the gene expression of brain
      derived neurotrophic factor (BDNF), the present results suggest that PTN may be
      an attractive protein to study further in the field of synaptic plasticity.

PMID- 15862928
TI  - Definition and classification of irritable bowel syndrome: current consensus and
      controversies.
AB  - The symptom-based taxonomy of IBS and other functional bowel disorders is based
      on defined individual symptoms and the co-occurrence of certain symptoms in
      individuals. Wording of survey questions to accurately reflect the symptoms can
      be difficult in English, but accomplishing it for non-English-speakers,
      especially residents of non-Western societies, is an even greater challenge that
      needs more attention. The potential for misdiagnosis and inappropriate
      management, including unnecessary surgery, under-scores the need for wider
      knowledge of typical IBS symptoms by physicians and the collaboration of primary
      and specialist physicians in patient care. Even though the evolving symptom
      classification is as evidence-based as its designers can make it, some
      arbitrariness is inevitable. Population prevalence rates vary widely, depending
      on diagnostic criteria and other factors, and further work is needed to determine
      which individuals detected in surveys consider themselves distressed enough to
      want medical care and why the remaining people do not feel this need. Clearly,
      more primary care patients should be studied. Physicians should assess clinical
      trials critically regarding patient recruitment methods and patient features that
      could influence whether the results are applicable to their patients. The
      instability of bowel habit subtypes suggests that relatively few patients should
      expect relief by taking the same motility-active drug regularly for a long time.
      Long-term, natural history studies of symptoms and health care use are needed.
      Discoveries of subtle morphologic pathology and disordered physiology are
      elucidating IBS pathophysiology further, which some experts believe will lead to
      a more objective, laboratory-based (organic) diagnosis and more effective
      therapy. The benefit patients will obtain from supplementing a traditional
      symptom-based, biopsychosocial approach with such findings remains to be
      determined. The symptom criteria have had important roles in epidemiological
      studies and characterizing subjects for clinical trials. Many practitioners,
      however,do not know the typical symptoms or use the criteria, and investigating
      how physicians diagnose IBS has received scanty attention. It is unknown how many
      physicians diagnose IBS by exclusion only after extensively testing patients with
      typical symptoms and no alarm features, but determining this could have important
      economic and safety implications. There has been little careful validation of the
      symptom criteria, especially with primary care patients, and no particular
      criteria are clearly superior for clinical practice,although the Manning and Rome
      I criteria have been most evaluated and are less restrictive than the Rome II
      criteria.

PMID- 15862926
TI  - Lactate infusion fails to improve semantic categorization in Alzheimer's disease.
AB  - Impaired neuronal energy metabolism, oxidative changes and microvascular
      abnormalities lead to altered lactate levels in Alzheimer's dementia. The aim of
      the present study was to assess whether intravenous sodium-lactate, a metabolic
      alternative and vasodilator that is thought to improve cognition, advances the
      cognitive performance of Alzheimer patients. Semantic categorization paradigm was
      used to present the electrophysiological correlates of natural scene
      categorization of Alzheimer patients before and after intravenous saline or
      sodium-lactate infusion. Mean amplitudes of event-related potentials (ERPs) were
      measured in two time windows before and after the treatments; two negative
      components (N1 between 150 and 250 ms and N2 between 400 and 600 ms) and one
      positive component (P2 between 250 and 400 ms) were identified. The negative
      components were more negative for the non-animal trials than for the animal
      trials while the positive component was similar for both categories. After the
      lactate treatment the amplitudes of the negative components became more negative
      mainly for the non-animal trials while the amplitude of the positive component
      turned more positive for the animal trials, however these changes were not
      significant. No changes have been observed after normal saline infusion. These
      results suggest that, contrary to its anticipated beneficial effects, sodium
      lactate fails to significantly improve semantic categorization processes in
      Alzheimer's disease and this enhancement can be detected by recording ERPs. The
      effect of sodium-lactate to slightly improve semantic memory might be based on
      its positive effect on cardio- and cerebro-vascular function and neuronal
      metabolism.

PMID- 15862929
TI  - Irritable bowel syndrome: epidemiology, natural history, health care seeking and
      emerging risk factors.
AB  - IBS is a common condition, affecting approximately 3% to 15% of the general
      population based on various diagnostic criteria. There seem to be differences in
      disease epidemiology between the eastern and the western world. As data from
      larger Asian epidemiological studies begin to surface,however, such differences
      appear to be less marked. The proportion of IBS patients who consult a physician
      for their symptoms is around 50%. Psychological factors and the presence and
      duration of abdominal pain are all significant predictors for health care
      seeking. The natural history of IBS is characterized by frequent fluctuation of
      symptoms and by an overlap with other functional GI disorders, some of which
      share a number of risk factors for IBS. Unnecessary abdominal surgery is
      performed in a high proportion of IBS sufferers. Along with the established role
      for psychosocial conditions in IBS, other risk factors are emerging. Evidence for
      postinfectious IBS is mounting, but the clinical usefulness of characterizing
      such patients remains unclear. Food sensitivities are frequently present in IBS,
      but more well-conducted trials of avoidance diets and desensitization are needed.
      Finally,genetic markers in IBS are an increasing focus of attention, but the
      amount of phenotypic variance explained by genetic variability remains to be
      established.

PMID- 15862930
TI  - Diagnosis of irritable bowel syndrome.
AB  - Because there are no reliable biological or laboratory markers associated with
      the condition, the diagnosis of irritable bowel syndrome(IBS) is based on patient
      descriptions of common symptoms such as abdominal pain accompanied by changes in
      stool form or frequency and associated symptoms such as bloating and distension.
      With the development and refinement of symptom-based criteria for the diagnosis
      of IBS, the traditional need for a negative diagnostic evaluation has been
      questioned. This article evaluates the diagnostic characteristics of various
      symptom-based criteria in routine clinical practice and reviews the data
      regarding the yield of the multiple commonly used diagnostic tests in patients
      with suspected IBS.

PMID- 15862931
TI  - Disturbances of motility and visceral hypersensitivity in irritable bowel
      syndrome: biological markers or epiphenomenon.
AB  - Motility and visceral hypersentitivity are regarded as the primary mechanisms of
      symptom development in irritable bowel syndrome(IBS). While a variety of motor
      abnormalities have been described throughout the gastrointestinal tract in IBS,
      their specificity and relationship to symptoms remain unclear. Visceral
      hypersensitivity is ubiquitous in functional gastrointestinal disease and is
      especially common in IBS. Again, however, its specificity for IBS has been
      questioned. Many factors, including stress and psychopathology,complicate the
      interpretation of these phenomena and new re-search suggests that mucosal
      inflammation and luminal factors may be more fundamental to the etiology of this
      common disorder.

PMID- 15862932
TI  - Is irritable bowel syndrome a low-grade inflammatory bowel disease?
AB  - Irritable Bowel Syndrome (IBS) is multifactorial in its etiology and
      heterogeneous in its clinical presentation and pathogenesis. It is recognized
      that inflammation plays an important role in symptom generation, at least in a
      subset of patients with IBS. Previous gastroenteritis has been identified as the
      most important risk factor for IBS, and several studies reported that a
      substantial proportion of patients with gastrointestinal infection develops IBS
      symptoms,which can persist for several years. Recent studies have demonstrated
      that a proportion of IBS patients without any history of enteritis has signs of
      immune activation in the gut. There is clinical overlap between IBS and
      inflammatory bowel disease (IBD), with IBS-like symptoms frequently reported in
      patients before the diagnosis of IBD, and a higher than expected percentage
      reports of IBS symptoms in patients in remission from established IBD. Thus,these
      conditions may coexist with a higher than expected frequency, or may exist on a
      continuum, with IBS and IBD at different ends of the same spectrum. This article
      examines these relation-ships using immune activation and inflammation as a
      common pathogenic process to IBD and a subset of IBS patients.

PMID- 15862933
TI  - The role of food intolerance in irritable bowel syndrome.
AB  - Irritable bowel syndrome patients frequently believe that food intolerances are
      to blame for many of their symptoms, although not uncommonly this is caused by
      the nonspecific increase in gut motility that occurs with food ingestion.
      Nevertheless, dietary manipulation may result in substantial improvement in IBS
      symptomatology provided it is individualized to the particular patient. By
      further understanding the mechanisms involved in dietary intolerance, it should
      be possible to optimize the benefits of this approach to treatment.

PMID- 15862934
TI  - The pathogenesis of bloating and visible distension in irritable bowel syndrome.
AB  - Abdominal bloating is a relevant, troublesome, and poorly understood clinical
      problem. Despite its clinical importance, bloating remains substantially ignored,
      without proper clinical classification, known pathophysiology, and effective
      treatment. It is not even clear to what extent the complaints of individual
      patients correlate with objective evidence of abdominal distension, and this
      uncertainly regarding the subjective or objective origin of the complaints
      further adds to confusion. This article proposed a framework for investigating
      bloating, considering key factors potentially involved in its pathophysiology:
      distorted sensation, physical abdominal expansion, and abdominal wall dystony.
      Some data indicate that patients complaining of bloating have impaired transit
      and tolerance of intestinal gas loads. The problem does not seem to be too much
      gas,however, but rather abnormal responses to gas. Furthermore, abnormal control
      of abdominal muscle activity in these patients may contribute to objective
      distension. Bloating, like many other abdominal symptoms,probably represents a
      heterogeneous condition produced by a combination of pathophysiological
      mechanisms that differ among individual patients,resulting in a polymorphic
      clinical presentation.

PMID- 15862935
TI  - Brain responses to visceral and somatic stimuli in irritable bowel syndrome: a
      central nervous system disorder?
AB  - In healthy subjects, the brain regions most consistently activated in visceral
      and somatic pain are the key regions in the central pain matrix,including the
      mid/anterior insula, subregions of the ACC, PFC, thalamus,and in some cases,
      pontine regions such as the dorsal pons and PAG. Functional neuroimaging studies
      have demonstrated evidence of altered regional brain activation responses during
      visceral and somatic stimuli in IBS that have been associated with perceptual
      differences. Although perceptual studies have shown increased sensitivity to
      rectosigmoid distension in IBS, most somatic pain studies have demonstrated
      normal or decreased sensitivity compared with controls; however, a recent study
      showed increased sensitivity to thermal heat. Altered brain responses in
      IBS,particularly to visceral stimuli, include activation of regions concerned
      with attentional processes and response selection, corticolimbic regions
      concerned with emotional and autonomic responses to stimuli, and subcortical
      regions receiving cortical projections from the latter and afferent input from
      the soma and viscera. Altered activations of these regions also may be present in
      the absence of a noxious visceral stimulus. Changes in rCBF of some of these
      regions have been associated with treatment response in IBS. With regard to
      differences in cortical processing of visceral versus somatic stimuli in IBS,
      there have been only two studies. Greater activations of the dorsal ACC,
      thalamus, and PFC have been shown with visceral stimuli compared with somatic
      stimuli in IBS. A plausible hypothesis for the observations from brain imaging
      studies is that IBS patients demonstrate a compromised activation of pain
      inhibition circuits including those of the cortico-pontine circuit but increased
      activation of limbic and paralimbic circuits that may be related to pain
      facilitation.

PMID- 15862936
TI  - Psychiatric and psychological dysfunction in irritable bowel syndrome and the
      role of psychological treatments.
AB  - Psychosocial variables play a substantial role in the IBS condition of many
      patients. Evaluating and addressing adverse psychosocial factors is important to
      achieve satisfactory clinical outcomes with those patients. This can be achieved
      efficiently through psychosocial interviewing, establishing a solid therapeutic
      relationship, and judicious and tactful application of psychotropic medications
      and psychological treatments. Success in address-ing psychosocial factors in
      clinical encounters benefits not only patients, but also the gastroenterologist
      through increased work satisfaction because of reduced difficulty and frustration
      in working with IBS patients.

PMID- 15862937
TI  - Genetics and genotypes in irritable bowel syndrome: implications for diagnosis
      and treatment.
AB  - Several twin studies and familial aggregation studies in IBS are consistent with
      either a genetic or a social learning hypothesis, and it is possible that both
      play a role. The prospect of identifying a genetic cause for IBS may be very
      important, because it raises the possibility of confirming that IBS isa disease
      entity, suggests new insight into the pathophysiology of the disorder, and
      provides new targets for drug development. Several candidate genetic markers
      including: those related to cytokines such as IL-10, TNF-alpha and TGF beta1;
      SERT-P; alpha-adrenergic receptors; and G proteins have been associated with
      certain aspects of IBS. Genetic polymorphisms,however, are common and may have no
      etiological or pathogenetic relevance. Searching for the genes in IBS is of
      potentially great relevance. Such studies may identify more specific phenotypes
      in IBS or potentially predict increased disease vulnerability, but it is unlikely
      that this strategy will lead to a diagnostic test, given the limited component of
      IBS that is likely to be genetically determined. Pharmaco genomic studies have
      potential to be important in the future. For this potential to be realized, it
      will be necessary to formally include genetic studies in trials of experimental
      drugs.This would enhance understanding of one of the roles of genetics for
      treating IBS.

PMID- 15862938
TI  - Efficacy of current drug therapies in irritable bowel syndrome: what works and
      does not work.
AB  - Based on current evidence, bulking agents are not more effective than placebo at
      improving global irritable bowel syndrome (IBS)symptoms, although they may
      increase stool frequency in large doses. Tricyclic antidepressants are more
      effective than placebo for patients with diarrhea-predominant IBS. Imodium is
      more effective than placebo at improving stool consistency and decreasing stool
      frequency in patients with IBS, and it may be an important component for treating
      diarrhea-predominant IBS. Antispasmodics agents available in the United States
      are not more effective than placebo for treating IBS, although the studies are
      small and poorly designed. There are no randomized controlled trials examining
      the efficacy of laxatives for managing IBS. Tegaserod is more effective than
      placebo at improving global IBS symptoms in women with nondiarrhea-predominant
      IBS. Alosetron is more effective than placebo in women with diarrhea-predominant
      IBS, although its use should be limited to patients who have failed conventional
      therapy because of its adverse event profile.

PMID- 15862939
TI  - Potential future therapies for irritable bowel syndrome: will disease modifying
      therapy as opposed to symptomatic control become a reality?
AB  - Irritable bowel syndrome can remit spontaneously, implying cure is possible.
      Predictors of good prognosis include a short history, acute onset(possibly
      postinfective origin), absence of psychological disorders, and resolution of
      chronic life stressors. Possible-disease modifying treatments with long-lasting
      effects include diet and anti-inflammatory and psychological treatments. Dietary
      modifications, which often involve excluding dairy and wheat products, are
      successful in some patients. Anti-inflammatory treatments have been subjected to
      one RCT in postinfective IBS without benefit. Probiotics may have benefit in
      altering bacterial flora and as anti-inflammatory agents, but further trials are
      needed before they can be recommended. Psychological treatments may produce long
      lasting responses. Relaxation therapy appears to have a nonspecific benefit.
      Psychotherapy has been shown to have long-term benefit and is particularly
      acceptable to, and effective for, those with overt psychological distress.
      Hypnotherapy has been shown to be effective in randomized placebo controlled
      trials and has a sustained effect.

PMID- 15862940
TI  - Update on the mechanisms and efficacy of biological therapies for psoriasis.
AB  - Biologically based agents (biologics) are novel therapeutic options in the
      treatment of moderate-to-severe psoriasis. Unlike traditional systemic anti
      psoriatic drugs, which are chemically synthesized, these agents are unique in
      that they are derived from living organisms and hence called "biologics." In
      addition, they are the first group of "custom-designed" molecules that precisely
      target steps in the pathogenesis of psoriasis. The specificity of these biologics
      can theoretically avoid the side effects of the prebiologically developed
      systemic agents including the effects of hepatotoxicity, nephrotoxicity, and bone
      marrow suppression. However, there is also a tendency for a more precisely
      targeted agent to have a less overall efficacy. Due to the varying efficacies and
      high costs of the new biologic agents that are currently approved for psoriasis
      in the United States, the precise way they fit into the range of treatments for
      moderate-to-severe psoriasis should be defined pending future clinical
      experiences.

PMID- 15862941
TI  - The hair growth promoting effect of Asiasari radix extract and its molecular
      regulation.
AB  - BACKGROUND: Hair loss is a distressing condition for an increasing number of men
      and women. It is of great importance; therefore, to develop new therapies for the
      treatment of hair loss. OBJECTIVE: We examined the effects of 45 plant extracts
      that have been traditionally used for treating hair loss in oriental medicine in
      order to identify potential stimulants of hair growth. METHODS: Six-week-old
      female C57BL/6 and C3H mice were used for evaluating the hair growth-promoting
      effects of the plant extracts. Topical application onto the backs of the C57BL/6
      and C3H mice was performed daily for 30 days and 45 days, respectively. Protein
      synthesis was measured by the cysteine uptake assay, using cultured murine
      vibrissae follicles. Proliferation of the immortalized human keratinocyte cell
      line (HaCaT) and human dermal papilla (DP) cells was evaluated by the MTT and
      thymidine incorporation assays. The mRNA levels of several growth factors that
      have been implicated in hair growth control were measured by reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: Among the tested plant
      extracts, the extract of Asiasari radix showed the most potent hair growth
      stimulation in C57BL/6 and C3H mice experiments. In addition, this extract
      markedly increased the protein synthesis in vibrissae follicle cultures and the
      proliferation of both HaCaT and human DP cells in vitro. Moreover, the A. radix
      extract induced the expression of VEGF in human DP cells that were cultured in
      vitro. CONCLUSION: These results suggest that the A. radix extract has hair
      growth-promoting potential, and that this effect may be due to its regulatory
      effects on both cell growth and growth factor gene expression.

PMID- 15862942
TI  - Rapid and specific identification of Sporothrix schenckii by PCR targeting the
      DNA topoisomerase II gene.
AB  - BACKGROUND: In order to study the genotype variation of Sporothrix schenckii, we
      previously analyzed the genomic sequences of the DNA topoisomerase II genes of
      this fungus and S. schenckii-related species, such as S. schenckii var. luriei
      and Ceratocystis stenoceras. OBJECTIVE: To develop a PCR-based identification
      system that can distinguish S. schenckii from its related species for clinical
      diagnosis of sporotrichosis. METHODS: Based on the nucleotide sequences of the
      DNA topoisomerase II genes of S. schenckii, S. schenckii var. luriei and C.
      stenoceras, three gene-specific primers (SSHF31 and SSHR97 for S. schenckii, and
      SSLF64 for S. schenckii var. luriei) were designed and evaluated for their
      specificities in PCR amplifications. RESULTS: The primer set SSHF31/SSHR97
      amplified PCR products of 663-817 bp from S. schenckii and approximately 660 bp
      from S. schenckii var. luriei, while SSLF64/SSHR97 exclusively amplified a major
      product of 305 bp from S. schenckii var. luriei. CONCLUSION: PCR targeting the
      DNA topoisomerase II gene specifically and rapidly distinguished S. schenckii
      from its related species.

PMID- 15862943
TI  - Reconstruction of human hair dermal papilla with microencapsulation in vitro.

PMID- 15862944
TI  - Expression of novel keratin associated protein 5 genes in the cuticle layer of
      human hair follicles.

PMID- 15862945
TI  - Identification of two functional estrogen response elements complexed with AP-1
      like sites in the human insulin receptor gene promoter.
AB  - This study was designed to explore the possible existence and location of
      estrogen response elements (EREs) in the human insulin receptor (hIR) gene
      promoter. Transfections of U-937 cells with the reported plasmids phIR(-1819)
      GL2, phIR(-1473)-GL2, and phIR(-876)-GL2, that contain the -1819 to -271 bp
      fragment of the hIR promoter (wild-type promoter) and progressive 5' deletions of
      this promoter, revealed that while the activity of the wild-type promoter, was
      repressed 36% by treatment with 17beta-estradiol (E(2)), the activities of
      progressive 5' deletions of this promoter were reduced by 26% and by 0%, by this
      hormone. This suggests that E(2) needs the wild-type promoter for full
      transcriptional repression of this gene and it also suggests the presence of
      putative EREs in the region between -1819/-877 bp of this promoter. To identify
      these EREs we performed a computer search, using the SEQFIND programme developed
      in our laboratory, by homology with the consensus vit-ERE (5'GGTCAnnnTGACC3') of
      the Xenopus vitellogenin A(2) gene promoter. The results of our search indicated
      no sequence identical to this consensus ERE, and neither was any sequence found
      to show 9 or 8 of the 10 bases of this consensus in this promoter. Nevertheless,
      a putative hIR ERE1 (5'AGTGAaacTGGCC3') showing 7 bases of the consensus vit-ERE,
      and 10 bases of the optimal binding sequence ERE (5'CA/GGGTCAnnnTGACCT/CG3'), was
      identified between -1430/-1418bp of the hIR promoter. An AP-1-like site was
      covering the 3' half-element of this ERE; another AP-1-like site was overlapping
      the first AP-1-like site, and finally a third AP-1-like site was located beside
      to the 5' half-element. In addition, another putative hIR ERE2
      (5'GCTCCtagCAAAC3') showing 5 bases of the consensus vit-ERE, and 9 bases of the
      optimal binding sequence ERE, was located upstream of the hIR promoter, between 
      1567/-1555 bp. An AP-1-like site was located downstream of the 3' half-element of
      this ERE, and another AP-1-like site was beside the 5' half-element. EMSA
      analysis using nuclear extracts of E(2)-treated cells and natural sequences,
      including these putative EREs, indicated that ERbeta - the only isoform expressed
      in U-937 cells - specifically recognized both EREs because ERbeta-DNA complexes
      were efficiently competed by the corresponding unlabelled probe and supershifted
      by the anti-human ERbeta (L-20) antibody. These data provide the first
      identification of EREs complexed with AP-1-like sites in the hIR promoter, which
      account for the transcriptional repression of the hIR gene mediated by ERbeta in
      U-937 cells.

PMID- 15862946
TI  - Cloning and characterization of the 5'-flanking region of the rat estrogen
      receptor beta gene.
AB  - In the rat, estrogen receptor (ER) beta is preferentially expressed in the ovary
      and the prostate gland where it is transcriptionally regulated by testosterone. A
      single 5'-end of rERbeta cDNA was identified in these tissues by the 5'-RACE
      analysis in the present study. The transcription starting site was predicted at 
      335 from the translation starting signal (ATG), and a 640bp section of the 5'
      flanking region of the gene was cloned. Luciferase reporter assays revealed this
      region to be responsible for cell-specific promoter activity and successive
      deletion analyses indicated that only 98bp were sufficient for basic promoter
      activity as well as for testosterone-dependent transcription. The sequence of the
      determined region found to demonstrate high homology with the mouse ERbeta
      promoter with more than 80% identity between positions -1 and -550. The rat
      region of -30/-110 also showed good homology with 69% identity to corresponding
      section of the human promoter. Putative cis-acting elements, USF/Arnt and AML1a,
      were found in common in the promoter regions of three species. The present study
      thus demonstrated the 5'-flanking region of the rERbeta gene to be a functional
      promoter.

PMID- 15862947
TI  - Selective hormone-dependent repression of estrogen receptor beta by a p38
      activated ErbB2/ErbB3 pathway.
AB  - Deregulated signaling of ErbB2 receptor tyrosine kinase is often associated with
      hormone resistance in estrogen receptor alpha (ERalpha)-positive breast cancers,
      establishing a relationship between ErbB2 and ERalpha pathways. Although ERalpha
      and ERbeta are expressed in many breast cancer cells, the response of ERbeta to
      ErbB2 signaling is less well defined. In the present study, we demonstrate that
      ERbeta activity can be modulated by ErbB2 signaling in ER-expressing breast
      cancer cells. The estrogen-dependent transcriptional activity of ERbeta was
      altered in a manner similar to ERalpha by either activation of ErbB2/ErbB3
      signaling by growth factor heregulin beta or expression of a constitutively
      active mutant of ErbB2. However, as opposed to ERalpha, the p38 MAPK pathway was
      found to be involved in liganded ERbeta repression activity by ErbB2 signaling
      and in regulating estrogen-responsive promoter occupancy by ERbeta. The
      repression in ERbeta response to hormone was dependent upon its AF-1 domain which
      includes serines 106 and 124, two phosphorylation target sites for Erk that we
      previously showed to be involved in SRC-1 recruitment to ERbeta. Substitution of
      these two serines by aspartic acid residues abolished the repression of ERbeta by
      activated ErbB2/ErbB3. Moreover, expression of SRC-1 also relieved the inhibition
      of ERbeta in heregulin-treated cells. Our study demonstrates a functional
      coupling between ERbeta and ErbB receptors and outlines the differential role of
      the AF-1 region in the regulation of the estrogen-dependent cell growth and
      activity of both estrogen receptors in response to growth factor signaling.

PMID- 15862948
TI  - Divergent effects of resveratrol, a polyphenolic phytostilbene, on free radical
      levels and type of cell death induced by the histone deacetylase inhibitors
      butyrate and trichostatin A.
AB  - We investigated the effects of the polyphenolic phytostilbene resveratrol on the
      steady-state free radical (FR) concentration and mode of cell death induced by
      the histone deacetylase inhibitors butyrate and trichostatin A. (i) There was no
      correlation between cell death induction by butyrate or trichostatin A (TSA) and
      FR levels. (ii) Treatment with resveratrol or N-acetyl-l-cystein (NAC) of cells,
      in which the FR concentration was high, resulted in an almost complete reduction
      of FR levels. (iii) When, however, the cellular FR concentration was marginal,
      resveratrol caused a minor, and NAC a marked increase of FRs as well as of the
      extent of cell death. Thus, resveratrol and NAC acted as antioxidants only when
      the cellular FR levels were high, and acted as pro-oxidants when facing a low FR
      concentration. (iv) Since resveratrol and the antioxidant NAC exhibited analogous
      effects, it is concluded that the observed actions of resveratrol are due to
      polyphenolic redox reactions and not related to the stilbene moiety of the
      molecule. (v) The results indicate that the redox status of a given cell type
      plays an important role in determining whether resveratrol and other antioxidants
      promote cell death or protect cells from it.

PMID- 15862949
TI  - Genomic organization of the CYP19b genes in the rainbow trout (Oncorhynchus
      mykiss Walbaum).
AB  - We report the occurrence of two CYP19b genes, namely CYP19b-I and CYP19b-II,
      encoding forms I and II of cytochrome P450aromB, the prevalently cerebral variant
      of aromatase in fish, in the nuclear genome of the rainbow trout. The CYP19b-I
      gene is 7.6 kbp-long, more than double the size of the known fish CYP19a and b
      genes, owing to the presence of three introns (1, 4 and 5) that enclose repeated
      sequences and are longer than 1 kbp. Unlike the CYP19a genes, but similarly to
      the CYP19b gene of the Nile tilapia, it contains 10, and not 9, exons, including
      an untranslated exon 1 (83 bp), as found also in the 5' non-coding region of
      mammalian CYP19 genes. The 5'-UTR is composed by exon 1 and the first 41 bp of
      exon 2 (150 bp), whose coding region covers the first 36 amino acid residues that
      incorporate the transmembrane domain. The CYP19b-II gene is only 2.5 kbp-long,
      because it contains only one intron, corresponding to the third intron of CYP19b
      I, and lacks also its first two exons. Thus, it encodes for a presumably soluble
      protein. Apart from this difference, the rest of the coding region is virtually
      the same as that of the CYP19b-I gene. The 5'-UTR corresponds in part to the 3'
      end (132 bp) of the second intron of the CYP19b-I gene, while the remaining
      portion (208 bp) bears no homology. CYP19b-II could be regarded as a pseudogene
      of the CYP19b-I gene, though it is unclear whether it is a processed or a
      duplicated pseudogene. Moreover, since it is transcriptionally active, it may
      retain a functional role for the overall brain aromatase activity in the rainbow
      trout.

PMID- 15862950
TI  - 2,5-Diphenylfuran-based pure antiestrogens with selectivity for the estrogen
      receptor alpha.
AB  - The estrogen receptor alpha (ERalpha) is understood to play an important role in
      the progression of breast cancer. Therefore, pure antiestrogens with a preference
      for this receptor form are of interest as new agents for the treatment of this
      malignancy. Several chemical structures with selective binding affinity for
      ERalpha have been identified and might be useful for the synthesis of ERalpha
      selective pure antiestrogens. In this study we applied the 2,5-diphenylfuran
      system which is closely related to the triphenylfurans described by others.
      Various side chains with amino and/or sulfur functions were linked to C3 to
      convert the furans to estrogen antagonists without residual estrogenic activity.
      The degree of alpha-selectivity which ranges from 2.5- to 236-fold is strongly
      influenced by the alkyl group at C4. Antiestrogenic potency was determined in MCF
      7/2a breast cancer cells stably transfected with a luciferase gene under the
      control of an ERE. The 2,5-bis(4-hydroxyphenyl)furan with an ethyl substituent
      and a 6-[N-methyl-N-(3-pentylthiopropyl)amino]hexyl side chain exerted the
      strongest antiestrogenic effect in this series with an IC(50) value of 50 nM in
      cells stimulated with 1 nM estradiol. The RBA values of this derivative were 18%
      (ERalpha) and 3.4% (ERbeta) of estradiol, respectively. It inhibited the growth
      of wild-type MCF-7 cells with an IC(50) value of 22 nM. The data show that the
      2,5-diphenylfuran system is appropriate for the development of pure antiestrogens
      with preference for ERalpha.

PMID- 15862951
TI  - Estrogen-related receptor expression in placenta throughout gestation.
AB  - Estrogen receptor (ER) alpha and beta mRNA levels increased from the first to the
      second trimester and then decreased until normal term delivery. Estrogen-related
      receptor (ERR) alpha, beta and gamma mRNA levels gradually increased up to the
      second trimester and then comparatively rapidly increased until normal term
      delivery. ERRs can bind to the steroid receptor coactivator family without any
      ligands and drive transcription activity of the target genes. The manner of ERR
      and ER gene expressions might show a competitive interaction associated with the
      use of common cofactors. It is speculated that the up-regulation of ERRs is
      related to placental growth after the down-regulation of ERs because of the
      remarkably high concentration of estrogens for ERs from the second trimester
      until delivery.

PMID- 15862952
TI  - Estrogen receptor alpha and beta subtype expression and transactivation capacity
      are differentially affected by receptor-, hsp90- and immunophilin-ligands in
      human breast cancer cells.
AB  - In MCF-7 (estrogen receptor (ER)+) and in MDA-MB-231 (ER-) cells stably
      transfected with either estrogen receptor alpha (ERalpha) or beta (ERbeta)
      subtype (MDA-MB-231 stably transfected with the mouse ERalpha cDNA (MERA) and MDA
      MB-231 stably transfected with the human ERbeta cDNA (HERB), respectively) N-term
      heat shock protein of 90kDa (hsp90) ligands (geldanamycin and radicicol) and C
      term hsp90 ligands (novobiocin) decrease the basal and estradiol (E(2))-induced
      transcription activity of ER on an estrogen responsive element (ERE)-LUC reporter
      construct concomitantly with or 1h after E(2) treatment. All hsp90 ligands
      induced an E(2)- and MG132-inhibited decrease of both ER cell content. However,
      the kinetics of these degradations are slower than those induced by the selective
      estrogen receptor down-regulator RU 58668 (RU). This suggests that inhibition of
      the hsp90 ATPase activity targets both ERs to the 26S proteasome and that hsp90
      interacts with both ER subtypes. Rapamycin (Rapa) and cyclosporin A (CsA),
      ligands of immunophilins FK506 binding protein (FKBP52) and cyclophilin of 40kDa
      (CYP40) interacting in separate ER-hsp90 complexes, both induced a proteasomal
      mediated degradation of ERs but not of their cognate immunophilin. Moreover, they
      also decrease the E(2)-induced luciferase transcription but weaker than RU and
      hsp90 ligands. Fluorescence activated cell sorter (FACS) analysis revealed a
      blockade of cell progression by RU and 4-hydroxy-tamoxifen at the G(1) phase of
      the cell cycle and an induction of apoptosis in MCF-7 cells. Rapa and mainly CsA
      (but not FK506) and hsp90 ligands promote by their own apoptosis in MCF-7, in
      MERA, and in HERB cells and in MDA-MB-231 ER-null cells. These data suggest that
      (1) hsp90, as for all steroid receptors, acts as a molecular chaperone for
      ERbeta; (2) ER-ligands (except tamoxifen), hsp90- and immunophilin-ligands
      (except FK506) target the two ER subtypes to a proteasome-mediated proteolysis
      via different signalling pathways; (3) hsp90- and immunophilin-ligands Rapa and
      CsA, alone or in association with anti-estrogens such as RU, may constitute a
      potential therapeutic strategy for breast cancer treatment.

PMID- 15862953
TI  - Quantitative analysis of estrogen receptor proteins in rat ovary.
AB  - The mRNAs of estrogen receptor beta (ERbeta), and its splice variant, ERbeta2,
      are abundant in granulosa cells in the ovary. With the use of antibodies, ERbeta
      protein has also been shown to be abundantly expressed, but to date no ERbeta2
      protein has been demonstrated in the ovary. ERbeta2 has a peptide, 18 amino acids
      in length, inserted into its ligand-binding domain, resulting in a reported 35
      fold reduction in its affinity for estrogen (E2). ERalpha, ERbeta1 and ERbeta2
      were quantified by Western blotting and by RT-PCR and their cellular localization
      in the ovary was examined by immunohistochemistry. In 3- and 5-week-old virgin,
      pregnant, lactating and post-lactating rats, the level of ERalpha protein ranged
      between 1.6 and 3.8 fmol/microg total protein. That of ERbeta was 8.8-11.2 and of
      ERbeta2, in the same samples, 4.1-5.9 fmol/microg total protein. ERbeta2 and
      ERbeta1 proteins were, therefore, present in approximately equal amounts in the
      ovary throughout the various reproductive stages. The major ERbeta proteins in
      rat ovary, detected by their molecular weights on Western blots, were ERbeta1-530
      and ERbeta2-548 (530+18 amino acids (aa)). Immunohistochemical staining revealed
      that ERbeta and ERbeta2 were expressed predominantly in granulosa cells of
      growing follicles, while ERalpha was found only in theca cells. In some theca
      cells, both ERalpha, ERbeta2 were expressed. The data suggests that in theca
      cells, where it is co expressed with ERalpha, ERbeta2 could function as a
      repressor of ERalpha. However, in granulosa cells where no ERalpha is detectable,
      and where E2 levels are high, ERbeta2, with its low affinity for E2, could be an
      important sensor through which E2 exerts regulatory control.

PMID- 15862954
TI  - Heat-induced degradation of overexpressed glucocorticoid receptor Separate
      protective roles of hsp90 and hsp70.
AB  - The glucocorticoid receptor (GR) occurs in cells in the form of a hormone
      responsive complex (HRC) with hsp90. The HRC is dynamic, with hsp90 constantly
      directing disassembly, and hsp70, assisted by hsp90, driving reassembly. WCL2
      cells stably overexpress GR to an extent that reduces the excess of hsp90 and
      hsp70 over GR by about 10-fold, compared to the ratio in HeLa cells. Yet the half
      lives of the HRC in WCL2 and HeLa cells are comparable. As a result, the rate of
      assembly in WCL2 is overwhelmed by accumulation of the non-hormone-binding form
      of GR in its complex with hsp70 and hsp90. This form comprised some 50% of total
      GR in WCL2 cells. When the cells were heated to 44 degrees C, the hormone-binding
      activity and solubility of GR fell in parallel, and the receptor formed heavy
      aggregates by sequestering large amounts of hsp70. About 40% of this aggregated
      receptor was degraded in cells recovering at 37 degrees C in the presence of
      cycloheximide. Concentration of GR protein increased with increasing induction of
      hsp70 following exposure to 41-44 degrees C. However, balance between hormone
      binding and inert forms of GR could shift in either direction in response to the
      increase or decrease of hsp90 induction, depending on the temperature.
      Suppression of degradation following re-exposure of the cells to 44 degrees C
      correlated better with induction of hsp90 than hsp70. We infer that sequestration
      of hsp70 by heat-unfolded receptor is the primary factor opposing degradation,
      while induction of hsp90 acts to further suppress degradation by accelerating HRC
      assembly.

PMID- 15862955
TI  - The hamster androgen receptor promoter: a molecular analysis.
AB  - The steroid/thyroid hormone receptors are members of a very large family of
      nuclear-activated transcription factors. These receptors play a crucial role in
      most biological function, including regulation of development, metabolism,
      behaviour and reproduction. Among androgen receptor (AR), we have recently
      demonstrated that its expression in the Harderian gland (HG) of the male hamster
      is under a well-co-ordinated cross-talk between various steroid hormone
      receptors. Here, are presented data on the sequence of hamster AR promoter region
      (5'UTR) and the molecular tools of its regulation. The 5'UTR is 1585 bp. The
      promoter region shows various responsive elements. Two putative CREM elements are
      present at -71 and -1576 bp. A putative retinoic acid responsive element is
      present at -1476 bp. An androgen/glucocorticoid responsive element is present at 
      473 bp. A putative thyroid hormone-responsive element at -381 bp and an estrogen
      responsive element at -230 bp. Also, a homopurinic stretch is evident between 
      1199 and -1118. Furthermore, Sp1 sites are also spread along the sequence. As
      well as for human, mouse, rat and pig, the hamster lacks the canonical promoter
      TATA and CCAAT boxes. Gel retardation experiments confirm the presence of active
      responsive elements for AR, estrogen receptor, glucocorticoid receptor and
      thyroid hormone receptor. Previous data on the regulation of expression of AR by
      other members of steroid/thyroid hormone receptors well correlate with sequence
      analysis and gel retardation experiments. Thus, androgens, thyroid hormone,
      stimulate the AR transcription, while synthetic glucocorticoid (Dex) and estrogen
      are potent inhibitors of AR expression. The comparison of hamster AR promoter
      sequence with other AR promoter shows an 89, 82, 84 and 84% identity with human,
      rat, mouse and pig AR promoter, respectively. These results, in the light of the
      extreme plasticity of hamster HG, suggest that the comparative study of
      expression and regulation of AR gene in the HG of the hamster offers a useful
      tool to approach the normal and pathological phenotype in human.

PMID- 15862956
TI  - Innovative drug delivery nanosystems improve the anti-tumor activity in vitro and
      in vivo of anti-estrogens in human breast cancer and multiple myeloma.
AB  - Anticancer drug efficiency is governed by its bioavailability. In order to
      increase this parameter, we synthesized several injectable and biodegradable
      systems based on incorporation of anti-estrogens (AEs) in nanoparticles (NPs) and
      liposomes were synthesized. Both nanospheres (NS) and nanocapsules (NCs, polymers
      with an oily core in which AEs were solubilized) incorporated high amounts of 4
      hydroxy-tamoxifen (4-HT) or RU 58668 (RU). Physico-chemical and biological
      parameters of these delivery systems, and coupling of polyethylene-glycol chains
      on the NP surface revealed to enhance the anti-tumoral activity of trapped AEs in
      a breast cancer MCF-7 cell xenograft model and to induce apoptosis. These
      features correlated with an augmentation of p21(Waf-1/Cip1) and of p27(Kip1) and
      a concomitant decrease of cyclin D1 and E in tumor extracts. Liposomes containing
      various ratios of lipids enhanced the apoptotic activity of RU in several
      multiple myeloma (MM) cell lines tested by flow cytometry. MM cell lines
      expressed both estrogen receptor alpha and beta subtypes except Karpas 620.
      Karpas 620 cells which did not respond to AEs became responsive following ER cDNA
      transfection. A new MM xenograft model was generated after s.c. injection of RPMI
      8226 cells in nude mice. RU-loaded liposomes, administered i.v. in this model, at
      a dose of 12mgRU/kg/week, induced the arrest of tumor growth contrary to free RU
      or to empty liposomes. Thus, the drug delivery of anti-estrogens enhances their
      ability to arrest the growth of tumors which express estrogen receptors and are
      of particular interest for estrogen-dependent breast cancer treatment. In
      addition it represents a new potent therapeutic approach for multiple myeloma.

PMID- 15862957
TI  - A letrozole-based dual aromatase-sulphatase inhibitor with in vivo activity.
AB  - The role of aromatase inhibitors in the treatment of hormone-dependent breast
      cancer is well established. However, it is now recognised that steroid sulphatase
      (STS) inhibitors represent a new form of endocrine therapy. To explore the
      potential advantage of dual inhibition by a single agent, we recently developed a
      series of dual aromatase-sulphatase inhibitors (DASIs) based on the aromatase
      inhibitor YM511. We report here a new structural class of DASI obtained by
      obtained introducing the pharmacophore for STS inhibition, i.e. a phenol
      sulphamate ester into another established aromatase inhibitor letrozole. Hence,
      the bis-sulphamate 9 was synthesised which exhibited IC(50) values of 3044 nM for
      aromatase and >10 microM for STS in JEG-3 cells. However, at a single oral dose
      of 10mg/kg, 9 inhibited aromatase and rat liver STS by 60% and 88%, respectively,
      24h after administration. A proposed metabolite of 9, carbinol 10, was
      synthesised. Despite also showing weak STS inhibition in JEG-3 cells, 10
      inhibited rat liver STS activity to the same extent as 9 at a single oral dose of
      10mg/kg. Thus, the concept of a letrozole-based DASI has been validated and could
      be further developed and modified for therapeutic exploitation.

PMID- 15862958
TI  - Estrogen-induced apoptosis in a breast cancer model resistant to long-term
      estrogen withdrawal.
AB  - Estrogen suppression through the use of an aromatase inhibitor is an effective
      endocrine treatment option for postmenopausal breast cancer patients with
      estrogen receptor (ER)-positive disease, however, there are concerns that long
      term estrogen deprivation will inevitably lead to resistance. To address the
      issue of acquired resistance to long-term estrogen deprivation our laboratory has
      developed an ER+/PR- hormone-independent breast cancer cell line, MCF-7:5C which
      is a variant clone of wild-type MCF-7 cells. Originally, these cells were
      cultured in estrogen-free MEM containing 5% charcoal-stripped calf serum and were
      found to be resistant to both estradiol (E(2)) and antiestrogens. Interestingly,
      a completely different phenomenon was observed when MCF-7:5C cells were cultured
      in phenol red-free RPMI 1640 medium containing 10% charcoal-stripped fetal bovine
      serum (SFS). Using DNA quantitation assays, we examined the effect of E(2) on the
      growth of MCF-7:5C cells under different media conditions. Our results showed
      that 10(-9)M E(2) caused a dramatic 90% reduction in the growth of MCF-7:5C cells
      cultured in RPMI medium containing 10% SFS but did not have any significant
      inhibitory effects on cells cultured in MEM media. Additional experiments were
      performed to determine whether the medium or the serum facilitated the inhibitory
      effects of E(2) and the results indicated that it was the serum. Annexin V and
      DAPI staining confirmed that the E(2)-induced growth inhibition of MCF-7:5C cells
      was due to apoptosis. We also examined the tumorigenic potential of MCF-7:5C
      cells by injecting 1x10(7)cells/site into ovariectomized athymic mice and found
      that these cells, previously cultured in RPMI media, spontaneously grew into
      tumors in the absence of E(2). Overall, these results show that low
      concentrations (>10(-11)M) of E(2) are capable of inducing apoptosis in an
      aromatase resistant breast cancer cell model and that this effect is highly
      influenced by the medium in which the cells are grown.

PMID- 15862959
TI  - Progesterone neuroprotection in spinal cord trauma involves up-regulation of
      brain-derived neurotrophic factor in motoneurons.
AB  - Progesterone (PROG) provides neuroprotection to the injured central and
      peripheral nervous system. These effects may be due to regulation of myelin
      synthesis in glial cells and also to direct actions on neuronal function. Both
      types of cells express classical intracellular PROG receptors (PR), while neurons
      additionally express the PROG membrane-binding site called 25-Dx. In motoneurons
      from rats with spinal cord injury (SCI), PROG restores to normal the deficient
      levels of choline acetyl-transferase and of alpha3 subunit Na,K-ATPase mRNA,
      while levels of the growth associated protein GAP-43 mRNA are further stimulated.
      Recent studies suggest that neurotrophins are possible mediators of hormone
      action, and in agreement with this assumption, PROG treatment of rats with SCI
      increases the expression of brain-derived neurotrophic factor (BDNF) at both the
      mRNA and protein levels in ventral horn motoneurons. In situ hybridization (ISH)
      has shown that SCI reduces BDNF mRNA levels by 50% in spinal motoneurons, while
      PROG administration to injured rats (4mg/kg/day during 3 days, s.c.) elicits a
      three-fold increase in grain density. In addition to enhancement of mRNA levels,
      PROG increases BDNF immunoreactivity in perikaryon and cell processes of
      motoneurons of the lesioned spinal cord, and also prevents the lesion-induced
      chromatolytic degeneration of spinal cord motoneurons as determined by Nissl
      staining. Our findings strongly indicate that motoneurons of the spinal cord are
      targets of PROG, as confirmed by the expression of PR and the regulation of
      molecular parameters. PROG enhancement of endogenous neuronal BDNF could provide
      a trophic environment within the lesioned spinal cord and might be part of the
      PROG activated-pathways to provide neuroprotection. Thus, PROG treatment
      constitutes a new approach to sustain neuronal function after injury.

PMID- 15862960
TI  - Regulation of aromatase and 5alpha-reductase by 25-hydroxyvitamin D(3), 1alpha,25
      dihydroxyvitamin D(3), dexamethasone and progesterone in prostate cancer cells.
AB  - Estrogens and androgens are proposed to play a role in the pathogenesis of
      prostate cancer. The effective metabolites, estradiol and 5alpha
      dihydrotestosterone are produced from testosterone by aromatase and 5alpha
      reductase, respectively. Metabolites of vitamin D have shown to inhibit the
      growth of prostate cancer cells. The aim of the present study was to verify
      whether 25-hydroxyvitamin D(3) (25OHD(3)), 1alpha,25-dihydroxyvitamin D(3)
      [1alpha,25-(OH)(2)D(3)], dexamethasone, and progesterone regulate the expression
      of aromatase and 5alpha-reductase in human prostate cancer cells. LNCaP and PC3
      cells were treated with 25OHD(3), 1alpha,25-(OH)(2)D(3), dexamethasone, or
      progesterone. Aromatase and 5alpha-reductase mRNA was quantified by real-time RT
      PCR and aromatase enzyme activity was measured by the [(3)H] water assay.
      Aromatase enzyme activity in LNCaP and PC3 cells was increased by both 10nM
      dexamethasone, 1-100 nM 1alpha,25-(OH)(2)D(3) and 100 nM-10 microM progesterone.
      The induction was enhanced when hormones were used synergistically. Real-time RT
      PCR analysis showed no regulation of the expression of aromatase mRNA by any
      steroids tested in either LNCaP or PC3 cells. The expression of 5alpha-reductase
      type I mRNA was not regulated by 1alpha,25-(OH)(2)D(3) and no expression of
      5alpha-reductase type II was detected in LNCaP.

PMID- 15862961
TI  - Aromatase inhibition by 15-deoxy-prostaglandin J(2) (15-dPGJ(2)) and N-(4
      hydroxyphenyl)-retinamide (4HPR) is associated with enhanced ceramide production.
AB  - Inhibition of aromatase activity is an established endocrine therapy in the
      treatment of hormone-dependent breast cancer. Recent studies on aromatase
      inhibition by the synthetic retinoid 4HPR, also known as fenretinide, and the
      PPARgamma agonist 15-dPGJ(2) have implicated a direct receptor-independent, redox
      sensitive mechanism of action. The signalling molecule ceramide has also been
      previously implicated as a negative regulator of aromatase activity. In the
      present study, we have investigated a potential mediatory role for this
      sphingolipid during aromatase inhibition by fenretinide and 15-dPGJ(2) in the
      breast cancer cell line MDA MB 231 and JEG-3 choriocarcinoma cells. 4HPR and 15
      dPGJ(2) caused a dose-dependent inhibition of aromatase activity associated with
      an increase in ceramide production. Both these actions were redox-sensitive as
      demonstrated by their abrogation in the presence of the anti-oxidant N
      acetylcysteine. Exogenous ceramide analogue mimicked these inhibitory actions on
      aromatase, but in a redox-independent manner. Blockade of the de novo ceramide
      production pathway by fumonisin B(1) or myriocin inhibited the ceramide
      responses, but did not prevent aromatase inhibition by 15-dPGJ(2) or 4HPR. This
      study highlights a potential role for aromatase inhibition and the stress
      response signal ceramide during the therapeutic actions of 15-dPGJ(2) and 4HPR in
      breast cancer treatment. However, these data do not support a mediatory role for
      this sphingolipid during aromatase inhibition by these agents.

PMID- 15862962
TI  - Regulation of aromatase activity by cytokines, PGE2 and 2-methoxyoestrone-3-O
      sulphamate in fibroblasts derived from normal and malignant breast tissues.
AB  - Synthesis of oestrone from androstenedione within tumours, by the aromatase
      enzyme complex, is an important source of oestrogen that is available to support
      the growth of hormone-dependent breast tumours. In view of the central role that
      the aromatase enzyme has in oestrogen synthesis there has been considerable
      interest in understanding its regulation and developing inhibitors to block its
      action. In the present study we have derived fibroblasts from breast tumours
      (TFs), tissue proximal to tumours (PFs) and reduction mammoplasty tissue (RMFs)
      and used them to investigate the regulation of aromatase activity by PGE(2), IL-6
      plus its soluble receptor (SR) or TNFalpha. In addition we have examined the
      ability of 2-methoxyoestrone sulphamate (2-MeOEMATE), a compound which alters
      microtubule stability, to block the stimulation of aromatase activity by these
      factors. Basal aromatase activity in PFs was significantly higher (p<0.001) than
      in TFs or RMFs. The combination of IL-6 plus SR or TNFalpha produced the greatest
      stimulation of aromatase activity in TFs (up to 61-fold) while having a much
      lower stimulatory effects on aromatase activity in PFs (up to 60% increase) or
      RMFs (up to 192% increase). 2-MeOEMATE reduced basal aromatase activity in TFs by
      87% and completely abrogated the ability of PGE(2), IL-6 plus SR or TNFalpha to
      stimulate aromatase activity in these fibroblasts. Results from these studies
      indicate that while PFs have the highest level of non-stimulated aromatase
      activity, aromatase activity in TFs shows the greatest response to cytokines.
      These findings suggest that intrinsic difference may exist for the different
      types of fibroblasts in the way in which they respond to regulatory factors. The
      ability of 2-MeOEMATE to block cytokine stimulated aromatase activity suggests
      that, in addition to its other anti-cancer properties, this compound may also act
      to inhibit cytokine-stimulated aromatase activity in breast tumours.

PMID- 15862963
TI  - Cloning and characterization of human form 2 type 7 17beta-hydroxysteroid
      dehydrogenase, a primarily 3beta-keto reductase and estrogen activating and
      androgen inactivating enzyme.
AB  - Type 7 17beta-HSD catalyzes the transformation of estrone (E1) into estradiol
      (E2) and dihydrotestosterone (DHT) into 5alpha -androstane-3beta,17beta-diol
      (3beta-diol) as well as zymosterone into zymosterol. This suggests that in
      addition to cholesterol metabolism, the enzyme could play a critical role in
      estrogen-sensitive cells, since it inactivates DHT that generally shows
      antagonistic effect in the cells, while producing active E2 for cell
      proliferation. In this report, we describe the cloning and characterization of a
      second form of type 7 17beta-HSD (17beta-HSD7_2) that shares 95.6% identity with
      17beta-HSD7_1. Using a 7.5kb genomic DNA fragment of 17beta-HSD7_1 as probe, we
      have obtained 7 BAC clones: three clones containing the 17beta-HSD7_1 gene and
      four containing the 17beta-HSD7_2 gene. The corresponding 17beta-HSD7_2 cDNA
      fragments of the coding region were obtained by amplification using RT-PCR and
      subcloned into pCMV expression vector and stably transfected into human embryonic
      kidney (HEK-293) cells. The overexpressed 17beta-HSD7_2 catalyzes efficiently the
      transformation of E1 into E2 and of DHT into 3beta-diol. Ribonuclease protection
      assays (RPA) indicate that 17beta-HSD7_2 is expressed in the liver, prostate,
      uterus and placenta. FISH mapping using the 7.5kb genomic DNA fragment as well as
      2 BAC clones of each form allowed us to map the 17beta-HSD7_1 gene on chromosome
      band 1q23, and 17beta-HSD7_2 on band 10p11.2. These results contrast with a
      previous report that the 17beta-HSD7_1 gene was mapped to chromosomal band
      10p11.2. This newly identified form of 17beta-HSD7 could have a significant role
      by modulating active hormone levels in estrogen-sensitive cells or tissues.

PMID- 15862964
TI  - Role of steroid hormones and prolactin in canine mammary cancer.
AB  - In several animal studies, prolactin has been found to be essential for mammary
      epithelial development, and its administration has been consistently shown to
      increase the rate of mammary tumours. High levels of steroid hormones have also
      been suggested to enhance mammary cancer development. The present study
      investigates the levels of the following hormones in serum and in tissue
      homogenates in dogs bearing canine mammary tumours: prolactin (PRL), progesterone
      (P4), dehydroepiandrosterone (DHEA), androstenedione (A4), testosterone (T),
      17beta-estradiol (17beta-E2) and estrone sulfate (S04E1). Eighty mammary tumours
      (40 dysplasias and benign and 40 malignant tumours) from 32 female dogs, and 10
      normal mammary glands from eight female dogs without history of mammary tumours,
      were analysed. Prolactin and steroid hormones in serum and tissue homogenates,
      were analysed by enzyme immunoassays (EIA) techniques, previously validated for
      this animal species. Levels of prolactin in tissue homogenates were significantly
      different between malignant and benign mammary tumours (p<0.01). Serum prolactin
      concentrations were lower in the control group as compared with the group of dogs
      with benign tumours and in dogs with malignant tumours (p=0.01). Serum prolactin
      levels in dogs with benign lesions were not significantly different than those
      obtained from dogs with malignant tumours. Levels of steroid hormones were
      significantly higher in malignant tumours compared with the benign tumours and
      normal mammary glands (p<0.01) both in serum and homogenate determinations. Our
      results suggest that the canine neoplastic mammary gland could be a source of
      prolactin. Our hypothesis is that both prolactin and steroid hormones are
      involved in the growth of canine mammary cancer, and that they might have an
      autocrine/paracrine role in the maintenance of this disease.

PMID- 15862965
TI  - Calcitriol inhibits growth response to Platelet-Derived Growth Factor-BB in human
      prostate cells.
AB  - Calcitriol, a hormonal form of Vitamin D, regulates growth of normal and cancer
      cells of various origins by modulation of peptide growth factors signaling.
      Platelet-Derived Growth Factor (PDGF) signaling pathway is involved in prostate
      cancer progression. We studied the expression of PDGF receptors in human prostate
      primary stromal cells and cancer epithelial cell lines and growth response to
      PDGF-BB isoform. We found that the expression of PDGF receptors and PDGF-BB
      mediated cell growth are regulated by calcitriol in prostate cells. Quantitative
      RT-PCR analysis revealed a lower level of mRNA for PDGF receptors in LNCaP and PC
      3 cells than in primary stromal cells. Western blotting showed a high amount of
      PDGFRalpha and beta proteins in primary stromal cells that could not be detected
      in LNCaP, which may explain the resistance of LNCaP cells to growth-promoting
      effect of PDGF-BB. Addition of Epidermal Growth Factor (EGF) to the culture
      medium induces the expression of PDGFRbeta and restores responsiveness of LNCaP
      to PDGF-BB to some extent. Calcitriol down-regulates PDGFRbeta expression and
      negatively regulates PDGF-mediated cell growth. Calcitriol does not affect
      PDGFRalpha and PDGF-B mRNA expression. We suggest that inhibition of PDGFRbeta
      expression by calcitriol might reduce responsiveness of prostate cells to
      mitogenic action of PDGF-BB.

PMID- 15862966
TI  - A20 gene expression is regulated by TNF, Vitamin D and androgen in prostate
      cancer cells.
AB  - A20 is a TNF-inducible primary response gene and its product, a zinc finger
      protein, has antiapoptotic function in several cancer cells. We studied A20 gene
      expression in the Vitamin D- and TNF-sensitive LNCaP cell line and in the Vitamin
      D- and TNF-resistant PC-3 cell line. The results of the quantitative real-time RT
      PCR analyses demonstrated that the basal level of A20 mRNA production in PC-3
      cells was considerably higher than in LNCaP cells that is associated with the
      resistance of PC-3 cells. TNF induced A20 gene expression in both cell lines, but
      with different effect. A20 mRNA expression was down-regulated by 10nM calcitriol
      within 3-9h after treatment and up-regulated by androgen reaching maximal values
      by 6h after stimulation in LNCaP cells. We conclude that A20 may be involved in
      the regulation of cell proliferation by TNF, Vitamin D, and androgen in prostate
      cancer.

PMID- 15862967
TI  - Yeast two-hybrid identification of prostatic proteins interacting with human sex
      hormone-binding globulin.
AB  - Yeast two-hybrid (Y2H) screening of a prostate cDNA library with the cDNA for sex
      hormone-binding globulin (SHBG) has been used to identify proteins through which
      SHBG may exert autocrine or paracrine effects on sex steroid target tissues. The
      library screen gave 230 positive interactions of which around 60 have been
      sequenced. Of the proteins identified to date from database (BLAST) searches of
      these sequences, SHBG is one of those occurring most frequently. Amongst the
      proteins of interest are the membrane-associated proteins flotillin-1 and PRV-1,
      the enzymes cathepsin D, kallikrein 4 and acid phosphatase, various
      metallothioneins and translation elongation factor 1 alpha. The significance of
      the interaction of SHBG with these proteins is discussed.

PMID- 15862968
TI  - Pronounced enhancement of glucocorticoid-induced gene expression following severe
      heat shock of heat-conditioned cells hints to intricate cell survival tactics.
AB  - We have previously reported that severe heat shock of HeLa cells stably
      transfected with a chloramphenicol acetyltransferase (CAT) gene, transcription of
      which is controlled by two glucocorticoid-responsive elements and a minimal
      promoter, pronouncedly enhanced glucocorticoid-induced CAT expression compared to
      that of non-heated cells, in spite of the glucocorticoid-receptor-mediated
      transcription of the gene being temporarily compromised by the shock. We now
      report that prolonged severe heat shock of properly heat-conditioned cells
      resulted in far more pronounced enhancement of glucocorticoid-induced CAT mRNA
      and protein expressions, in spite of a similar heat-induced loss of receptor
      mediated CAT gene transcription. During recovery from the shock the hormonal
      activation of transcription exceeded that of non-heated cells. While CAT mRNA
      translation was restored appreciably later than CAT gene transcription, mRNA and
      protein expressions were thermally enhanced to a comparable extent, consistent
      with the integrity of CAT mRNA being preserved during recovery. CAT mRNA turnover
      was fully impaired during early recovery, suggesting that stabilisation of CAT
      mRNA as well as stimulation of the hormonal activation of CAT gene transcription
      account for the thermal enhancement of glucocorticoid-induced CAT expression.
      This data hint to cell survival tactics designed to safeguard high expression of
      genes of stress-enduring function.

PMID- 15862969
TI  - The effects of 2-methoxyoestrogen sulphamates on the in vitro and in vivo
      proliferation of breast cancer cells.
AB  - 2-Methoxyoestrogen sulphamates are a new class of compounds, which inhibit breast
      cancer cell proliferation and are also potent inhibitors of steroid sulphatase
      (STS) activity. In the present study, we have used two cell proliferation assays
      (MTS and AB) to identify potent new compounds in this class. Similar IC(50)
      values were obtained using these assays with two of the most potent compounds
      identified being 2-methoxyoestradiol-bis-sulphamate (2-MeOE2bisMATE) and 2
      methoxyoestradiol-17beta-cyanomethyl-3-O-sulphamate (2-MeOE2CyMATE). Both
      compounds inhibited the proliferation of MCF-7 (ER+) and MDA-MB-231 (ER-) breast
      cancer cells. Using the AB assay, which allows repeat measurements of cell
      proliferation without killing cells, both compounds were shown to inhibit cell
      proliferation in an irreversible manner. As STS may be involved in the removal of
      the sulphamoyl moiety of these compounds, which could reduce their potency, their
      ability to inhibit the proliferation of MCF-7 cells transfected with the cDNA for
      STS was also examined. Although the STS activity was 20-fold higher in these
      cells than in non-transfected MCF-7 cells, no decrease in the ability of these
      compounds to inhibit cell proliferation was detected. To test the efficacy of
      these compounds in vivo, nude mice were inoculated with MCF-7 cells in Matrigel
      and stimulated to grow with oestradiol. Three weeks after the oral administration
      of 2-MeOE2bisMATE or 2-MeOE2CyMATE (20mg/kg/day, 5 days/week) tumour volumes had
      regressed by 52% and 22%, respectively. Both compounds also inhibited liver and
      tumour STS activity by >90%. The potent anti-proliferative effects of these
      compounds, and their ability to inhibit tumour growth and STS activity in vivo,
      indicates that they are suitable for development as novel therapeutic agents,
      which should be active against a wide range of cancers.

PMID- 15862970
TI  - The nature of inhibition of steroid sulphatase activity by tibolone and its
      metabolites.
AB  - Tibolone is used for hormone replacement therapy and acts in a tissue-specific
      manner being oestrogenic on CNS and bone but not on breast tissues or
      endometrium. The ability of tibolone and its metabolites to inhibit steroid
      sulphatase (STS) activity has a crucial role in regulating its tissue-specific
      effects. In this study, we have examined the ability of tibolone and its non
      sulphated and sulphated metabolites to inhibit STS activity in different enzyme
      preparations and in intact cells. For this, we have used an 'extracellular'
      method, which measures the amount of product released into culture medium, and an
      'intracellular' method, which assesses the extent of product formation within
      cells. In addition, the nature by which tibolone and some of its metabolites
      inhibit STS activity was investigated using intact cells and an enzyme kinetic
      method. In MCF-7 and T47D breast cancer cells and JEG-3 choriocarcinoma cells,
      which have high STS activity, tibolone and its metabolites were relatively potent
      inhibitors of STS activity (33-57% inhibition at 10 microM) using the
      extracellular assay method. In HOS-TE-85 osteoblast-like cells, tibolone and its
      Delta-4 metabolite were relatively inactive whereas the 3alpha/3beta-hydroxy
      metabolites and their sulphated conjugates inhibited activity by 39-55%. When STS
      activity was assessed in HOS-TE-85 cells using an 'intracellular' method tibolone
      and its 3beta-hydroxy metabolite were inactive. Pre-treatment of breast cancer
      cells and JEG-3 cells, and removal of drugs prior to assaying for STS activity,
      revealed that in these cells tibolone and its metabolites were acting mainly as
      reversible inhibitors. This finding was confirmed in an enzyme kinetic study to
      measure concentration-dependent STS inhibition. In HOS-TE-85 cells, pre-treatment
      of cells and removal of compounds before assaying for remaining STS activity
      indicated that some tibolone metabolites appeared to stimulate STS activity.
      Possible mechanisms by which this might occur are discussed but, if confirmed,
      this could contribute to the positive oestrogenic effects that tibolone has on
      bone.

PMID- 15862971
TI  - Anti-cancer activities of novel D-ring modified 2-substituted estrogen-3-O
      sulfamates.
AB  - Sulfamoylated derivatives of the endogenous estrogen metabolite 2
      methoxyestradiol (2-MeOE2 (7)), such as 2-methoxy-3-O-sulfamoyl estrone (2
      MeOEMATE (1)), display greatly enhanced activity against the proliferation of
      human cancer cells and inhibit steroid sulphatase (STS), another current oncology
      target. We explore here the effects of steroidal D-ring modification on the
      activity of such 2-substituted estrogen-3-O-sulfamates in respect of inhibition
      of tumour cell proliferation and steroid sulphatase. The novel 17-deoxy analogues
      of 2-MeOEMATE and the related 2-ethyl and 2-methylsulfanyl compounds showed
      greatly reduced inhibition of MCF-7 proliferation. Introduction of a 17alpha
      benzyl substituent to such 2-substituted estrogen sulfamates also proved
      deleterious to anti-proliferative activity but could, in one case, enhance STS
      inhibition with respect to the parent substituted estrone sulfamate. In contrast,
      selected 17-oxime derivatives of 2-MeOEMATE displayed an enhanced anti
      proliferative activity. These results illustrate that enhanced in vitro anti
      cancer activity can be achieved in the 2-substituted estrogen sulfamate series
      and highlight, in particular, the importance of potential hydrogen bonding
      effects around the steroidal D-ring in the activity of these molecules. The SAR
      parameters established herein will assist the future design of anti-proliferative
      and anti-endocrine agents as potential therapeutics for both hormone dependent
      and independent cancers.

PMID- 15862972
TI  - Inhibition of human-type 1 3beta-hydroxysteroid deshydrogenase/Delta(5)-Delta(4)
      isomerase expression using siRNA.
AB  - Specific inhibition of type 1 3beta-HSD is of particular interest since it will
      allow us to control the formation of androgens and estrogens in peripheral target
      tissues without affecting type 2 3beta-HSD, which is responsible for the
      biosynthesis of glucocorticoids and mineralocorticoids in the adrenals. The high
      homology between types 1 and 2 3beta-HSD is a major difficulty in the development
      of specific inhibitors through classical chemical synthesis. In this report, we
      describe the use of small interference RNA (siRNA) to specifically inhibit human
      type 1 3beta-HSD. We have constructed three DNA vector-based RNAi vectors that
      allow us to produce three RNA duplexes of 21 nucleotides targeting three
      different coding regions of human type 1 3beta-HSD mRNA. The resulting constructs
      were co-transfected into HEK-293 cells with a vector expressing type 1 3beta-HSD.
      The results indicate that while the two duplexes that target sequences in the 5'
      region do not have a strong inhibitory effect, the duplex that targets the 3'
      region efficiently inhibits 3beta-HSD activity. Up to 98% inhibition has been
      observed. To our knowledge, this is the first report showing successful
      inhibition of steroidogenic enzymes using siRNA technology.

PMID- 15862973
TI  - Promoter analyses of human and mouse 17beta-hydroxysteroid dehydrogenase type 7.
AB  - In this study we examined and compared the 5' flanking regions (promoter regions)
      of human and murine 17beta-hydroxysteroid dehydrogenase type 7 genes (HSD17B7).
      In 1998, this enzyme was described to convert estrone to biologically more active
      estradiol. However, in 2001, it was predicted to be involved in cholesterol
      biosynthesis. To elucidate the mechanism governing HSD17B7 expression and its
      function, we analyzed the promoter regions by bioinformatic and experimental
      approaches. Our study provides new insights to the transcriptional regulation of
      HSD17B7 and further hints to its involvement in cholesterol biosynthesis.

PMID- 15862974
TI  - The effect of dehydroepiandrosterone sulfate and allopregnanolone sulfate on the
      binding of [(3)H]ifenprodil to the N-methyl-d-aspartate receptor in rat frontal
      cortex membrane.
AB  - Neurosteroids have been shown to modulate the N-methyl-d-aspartate (NMDA)
      receptor function. Dehydroepiandrosterone sulfate (DHEAS) is shown to participate
      in memory and learning processes as well as preventing glutamate neurotoxicity in
      hippocampus. In this study we have focused on the modulatory effect of
      neurosteroids on ifenprodil binding to the NR2B subunit of the NMDA receptor. We
      show that DHEAS and allopregnanolone sulfate (ALLOPREGS) exert different effects
      on the [(3)H]ifenprodil binding at 10, 30 or 100 nM, corresponding to
      physiological concentrations. The effects include changes in the ifenprodil
      displacement curve, changing it from a one-site fit into a two-site fit leaving
      B(max), K(d) and K(off) unaffected. Our results indicate that DHEAS and ALLOPREGS
      induce an allosteric modulation of the NMDA receptor, an observation that might
      contribute to the understanding of the effects of these neurosteroids.

PMID- 15862975
TI  - Changes in the content of steroid receptor coactivator-1 and silencing mediator
      for retinoid and thyroid hormone receptors in the rat brain during the estrous
      cycle.
AB  - In this work, we determined the variations in the content of the steroid receptor
      coactivator (SRC-1) and the silencing mediator for retinoic acid and thyroid
      hormone receptors corepressor (SMRT) in the hypothalamus, the preoptic area, and
      the hippocampus of adult intact rats during the estrous cycle by Western blot.
      SRC-1 content changed only in the hypothalamus where its lowest content was found
      on diestrus day with a significant increase at proestrus. This increase was
      maintained on estrus day. In contrast, SMRT content changed only in the preoptic
      area where it diminished at metestrus in comparison with the other days of the
      cycle. SRC-1 content was higher than that of SMRT in the hypothalamus throughout
      the estrous cycle, whereas SMRT content was higher in the preoptic area. In the
      hippocampus, there were no significant differences in the content of any
      cofactor. These results demonstrate that SRC-1 and SMRT content change in a
      tissue-specific manner in the rat brain during the estrous cycle, and suggest
      that the transcriptional activity of steroid hormone receptors in the rat brain
      in physiological conditions is regulated by changes in SRC-1 and SMRT content.

PMID- 15862976
TI  - 11beta-Hydroxysteroid dehydrogenase in the heart of normotensive and hypertensive
      rats.
AB  - Corticosteroids have been shown to play a role in cardiac remodeling, with the
      possibility of a direct effect of overexpression of 11beta-hydroxysteroid
      dehydrogenase (11HSD) isoform 2 at the level of the cardiomyocytes. The aim of
      this study was to examine cardiac steroid metabolism in hypertensive rats with
      hearts that are hypertrophied and fibrotic and have structural alterations in the
      coronary circulation. To assess possible alterations of cardiac steroid
      metabolism the expression and activity of both isoforms of 11beta-hydroxysteroid
      dehydrogenase (11HSD) were studied in spontaneously hypertensive rats (SHR),
      their normotensive controls Wistar-Kyoto (WKY), and in Dahl salt-sensitive (DS)
      and salt-resistant rats (DR) kept on a low- or high-salt diet. Using real-time
      quantitative RT-PCR and enzyme activity assay we found strain-dependent
      differences in cardiac metabolism of glucocorticoids. In Dahl rats expression of
      11HSD1 and 11HSD2 mRNA was lower in DS than in DR rats and was not influenced by
      dietary salt intake; 11HSD1 mRNA was expressed at higher level than 11HSD2 mRNA.
      NADP(+)-dependent cardiac 11HSD activity showed similar distribution as 11HSD1
      mRNA-lower activity in DS than in DR rats and no effect of salt intake. In SHR
      and WKY strains 11HSD2 mRNA expression was significantly higher in WKY than in
      SHR but no differences were observed in 11HSD1 mRNA abundance and NADP(+)
      dependent 11HSD activity. These results show that the heart is able to metabolize
      glucocorticoids and that this metabolism is strain-dependent but do not support
      the notion of association between cardiac hypertrophy and changes of 11HSD1 and
      11HSD2 expression.

PMID- 15862977
TI  - Temporary staff.

PMID- 15862978
TI  - Child restraint misuse: a case example and strategies for injury prevention.
AB  - Motor vehicle crashes are a leading cause of death and serious injury for
      children. Emergency nurses can play a key role in encouraging parents and
      caregivers to use child restraints consistently and correctly. This article will
      discuss a case scenario where a young child is seriously injured in a motor
      vehicle crash where his child car seat was not used correctly. Injury prevention
      strategies for emergency nurses will be reviewed.

PMID- 15862979
TI  - Rapid assessment and initial patient treatment team -- a way forward for
      emergency care.
AB  - As a consequence of the UK Department of Health drive to introduce the 4-h
      emergency care target acute trusts have attempted to initialize a myriad of
      programmes to improve the patients' experience in this sector. Changes to how
      patients are managed and the flow that they enter within the emergency care
      system have become a popular option. This paper seeks to explore the concept of
      the Rapid Assessment and Initial Patient Treatment team (RAPT) within the
      Accident and Emergency (A and E) environment. We intend to provide information
      for readers who may be considering introducing such teams. The paper will explore
      the initial practical difficulties that were encountered. We will explore
      associated benefits for the RAPT approach including improved teamwork, better
      communication with the family, avoiding unnecessary duplication of work and
      discuss the benefits of having a direct referral process in place for emergency
      patients.

PMID- 15862981
TI  - The role of Victorian emergency nurses in the collection and preservation of
      forensic evidence: a review of the literature.
AB  - Emergency Departments (ED) are providing care for increasing numbers of patients
      who present as a result of criminal or interpersonal violence and patients may be
      victims, suspects or perpetrators. As a result, the role of emergency nurses in
      the recognition, collection and preservation of forensic evidence is increasing.
      There is little published literature about the role and responsibilities of
      emergency nurses regarding the collection and preservation of evidence in the
      state of Victoria and this is complicated by a lack of department and
      organisation policy and the need for more specific educational preparation of
      emergency nurses in this area. While it is well accepted that the primary focus
      of nursing care will always be the physical and emotional care of the patient,
      the increasing importance of the role of emergency nurses in the recognition and
      collection of forensic evidence in Victoria is now being recognized and the need
      for education of emergency nurses in this area understood. This paper reviews the
      literature related to the recognition, collection and preservation, of forensic
      materials in EDs by emergency nurses in the state of Victoria and discusses the
      role of emergency nurses in Victoria in caring for patients who present as
      victims of violence and in whom the collection and preservation of forensic
      evidence is required.

PMID- 15862982
TI  - Preparing for the Diploma in Immediate Medical Care of the Royal College of
      Surgeons of Edinburgh.
AB  - The Diploma in Immediate Medical Care of The Royal College of Surgeons of
      Edinburgh is recognized as the current 'gold standard' assessment for pre
      hospital care practitioners. This article discusses the format of the examination
      and offers potential candidates advice on preparing for it.

PMID- 15862983
TI  - What every emergency nurse needs to know about aspirin.
AB  - As the most commonly recommended medication in the world, aspirin is a medication
      with which emergency nurses are intimately familiar. Although this medication has
      been used for more than a century, health-care researchers are discovering new
      information about the utility of aspirin every year. Within this paper, we
      provide a review of recent findings related to the use of aspirin in the
      Emergency Department. In particular, we focus on understanding the
      pharmacokinetics of the medication as several drugs introduced in the past
      decade, interact with aspirin and create side effects harmful to patients. As
      well, we highlight current research around optimal dosage and other issues
      related to aspirin administration. This review is timely as several issues have
      arisen in the literature, in relation to the effectiveness of aspirin as an anti
      platelet agent.

PMID- 15862984
TI  - The experience of a good day: a phenomenological study to explain a good day as
      experienced by a newly qualified RN.
AB  - The main aim of this study was to provide an explanation of the newly qualified
      nurse's experience and description of a good day. Secondly, it sought to provide
      an explanation of how a good day made them feel about nursing. By identifying the
      main components of a good day and what positively effects the experience of a
      working day for a newly qualified nurse, it may be possible to move towards an
      increase in the occurrence of the components and emulation of a good day. While
      there is evidence to suggest that positive experiences within nursing increase
      job satisfaction and aid retention to the profession, the experience of a good
      day and what constitutes a good day for a newly qualified nurse has not been
      explored. The main components of a good day have not been identified and no work
      has been carried out to ascertain how these days make nurses feel about their
      chosen career. The aims of the study lent themselves to a phenomenological
      descriptive approach to research, the objective of which is identification of the
      essence of behaviour. Eight newly qualified nurses agreed to take part in the
      research. Each participant was interviewed twice, and in addition one group
      interview was arranged to clarify themes. The interviews, which were audio taped,
      were informal allowing the participants to answer in an open and unstructured
      manner. Once completed, all the tapes were transcribed and immersion and analysis
      of the data led to 5 themes naturally emerging as the components of a good day.
      The identified themes were, doing something well, good relationships with
      patients, feeling that you've achieved something, getting the work done and you
      need team work. In addition, although not a theme of a good day but of great
      importance was the description of 'that wonderful feeling at the end of a good
      day'. These themes contributed to feelings of job satisfaction and the pleasure
      of nursing. More specifically the concept of knowing the patient both from a
      personal level and knowing about their care and condition has been identified as
      a main component of a good day. This knowing the patient had a knock on effect in
      that when this was part of the day it was easier to prioritize and get the work
      done. These nurses were striving to develop a level of care and competency and,
      unlike expert nurses, did not have vast experience and knowledge to underpin
      their actions. They need to ensure that all levels of knowledge are addressed
      before they can carry out care. Additionally, the team dynamics and the way the
      team work together had a significant effect on the day.

PMID- 15862985
TI  - A retrospective chart review of adult mortality characteristics of patients
      presenting to a principal tertiary emergency department.
AB  - AIM: To determine the incidence of death after arrival to one metropolitan
      emergency department (ED) for each triage code, day of arrival, diagnosis and
      length of stay. METHOD: A 12-month retrospective chart review was conducted in a
      550 bed principal referral hospital of all patients that presented to the ED and
      subsequently died. The ED annual attendance rate for the study year was 46,017
      patients. The data collected included patient demographics, diagnosis, triage
      code, length of stay and ward disposition. The data are expressed as proportions,
      percentages, frequencies or the statistic chi-square (chi(2)). The proportion of
      ED deaths also examined included those patients admitted through the ED to a ward
      area. RESULTS: The ED mortality rate for the study period was 1.3% (n=595). One
      hundred and twenty-three patients (21%) died in the unit, while 472 (79%) were
      admitted through the ED to a ward area. The total annual hospital mortality rate
      was 1.7% (n=790). The mean age of patients that died was 76 years. Of ED deaths,
      329 (55%) were male and 266 (45%) female. Triage code 1 (60%) was allocated more
      commonly to patients that died in the ED compared with triage code 3 (46%) for ED
      Ward deaths. CONCLUSIONS: Examination of ED mortality rate provides a deeper
      understanding of service utilisation and nursing staff work performance. Triage
      codes are beneficial in evaluating ED services, casemix, policies and quality
      assurance activities, but the application of this indicator to in-patient
      services appears limited.

PMID- 15862986
TI  - The identification of osteoporosis in patients presenting with low-impact
      fracture: a pilot study of a method for identification of these patients.
AB  - OBJECTIVES: To assess the use of a portable ultrasound unit in screening for
      osteoporosis in older patients presenting to the Emergency Department (ED) with
      low-impact fractures. METHOD: All patients over 65 years with a possible low
      impact fracture were to be identified and screened. Full ethical approval was
      obtained. An initial pilot study of "non-osteoporotic" ED staff was carried out
      before the full study was to occur. RESULTS: The pilot study showed portable
      ultrasound measuring proximal phalanx bone mineral density lacked both precision
      and accuracy. CONCLUSIONS: The aims of the study were worthwhile. However, the
      initial pilot study showed that the tools were inadequate for a full study. The
      full study was abandoned and new ways of identifying these patients are being
      looked at.

PMID- 15862987
TI  - Identifying non-accidental injury in children presenting to A&E departments: an
      overview of the literature.
AB  - BACKGROUND: The need for an effective system of child protection, which is able
      to detect children at risk of physical abuse, has never been more urgent. The
      level of reporting of non-accidental injury (NAI) in young children is lower than
      would be expected from official statistics, which means that Accident and
      Emergency (A and E) nurses and clinicians have a special responsibility to
      improve detection of possible abuse, in what has become a very challenging area
      of medicine. AIMS: In this paper, we review the main issues facing clinicians and
      nurses in the identification of children at risk of NAI and discuss the policy
      implications affecting A and E departments. In particular we ask the question:
      what are the factors that influence the identification and reporting of suspected
      NAI in young children and how can the under-recognition of NAI be improved?
      CONCLUSION: We conclude that organisational changes, such as the creation of a
      shared national database and improved training for A and E staff so that they are
      aware of social as well as clinical risk factors, are needed to address the under
      reporting of non-accidental injury in young children.

PMID- 15862989
TI  - Stereocontrolled synthesis of anticancer beta-lactams via the Staudinger
      reaction.
AB  - Stereocontrolled synthesis of novel beta-lactams using polyaromatic imines
      following the Staudinger reaction has been accomplished. The effects of domestic
      microwave irradiation on this type of reaction have been investigated. Formation
      of trans-beta-lactams has been explained through isomerization of the enolates
      formed during the reaction of acid chloride (equivalent) with imines in the
      presence of triethylamine. A donor-acceptor complex pathway is believed to be
      involved in the formation of cis-beta-lactams. The effect of a peri hydrogen has
      been found to be significant in controlling the stereochemistry of the resulting
      beta-lactams. SAR has identified beta-lactams with anticancer activity. The
      presence of an acetoxy group has proven obligatory for their anticancer activity.

PMID- 15862990
TI  - Synthesis and in vivo evaluation of a new PET radioligand for studying sigma-2
      receptors.
AB  - The cyclohexyl piperazine 1 (1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydro
      naphthalen-1-yl)-propyl]-piperazine) has been shown to be a potent and selective
      sigma-2 receptor ligand. In the present study, we prepared [(11)C]1 by O
      alkylation of the phenolic precursor 2 with [(11)C]CH(3)I. [(11)C]1 was obtained
      in a 29% non-decay corrected yield and specific activity of 9299 mCi/micromol
      calculated at end-of-synthesis. The biodistribution of [(11)C]1 in mouse brain
      demonstrated rapid and homogenous concentration in all brain structures, which
      included the cortex, thalamus, cerebellum and striatum. Co-administration of
      unlabelled 1 (1 mg/kg) or the sigma-2 selective ligand SM-21 (1 mg/kg) failed to
      show any significant inhibition of [(11)C]1 uptake in the mouse brain. The
      evaluation of this radioligand in vivo in the mouse clearly indicates that it
      does not possess the required properties for studying sigma-2 receptors in the
      brain using PET.

PMID- 15862991
TI  - Design and synthesis of complementing ligands for mutant thyroid hormone receptor
      TRbeta(R320H): a tailor-made approach toward the treatment of resistance to
      thyroid hormone.
AB  - The thyroid hormone receptors (TR) are ligand-dependant transcription factors
      that regulate key genes involved in metabolic regulation, thermogenesis and
      development. Resistance to thyroid hormone (RTH) is a genetic disease associated
      with mutations to TRbeta that lack or show reduced responsiveness to thyroid
      hormone (triiodothyronine). Previously we reported that the neutral alcohol-based
      thyromimetic HY-1 can selectively restore activity to a functionally impaired
      form of TR associated with RTH without over-stimulating TRalpha, which has been
      associated with undesirable side effects. Two new series of tetrazole and
      thiazolidinedione based ligands were evaluated for their ability to recover
      potency and efficacy to three of the most common RTH-associated mutants,
      TRbeta(R320C), TRbeta(R320H), and TRbeta(R316H), in cell based assays. A new
      thiazolidinedione based ligand AH-9 was identified, which has near wild-type
      potency (EC(50)=0.54 nM) to TRbeta(R320C) and TRbeta(R320H). Significantly, AH-9
      is equipotent toward TRalpha(wt), TRbeta(wt), TRbeta(R320C), and TRbeta(R320H),
      suggesting that AH-9 may have the potential to restore the normal homeostatic
      balance of thyroid hormone actions in patients or models harboring these
      mutations.

PMID- 15862992
TI  - Proteins Markovian 3D-QSAR with spherically-truncated average electrostatic
      potentials.
AB  - Proteins 3D-QSAR is an emerging field of bioorganic chemistry. However, the large
      dimensions of the structures to be handled may become a bottleneck to scaling up
      classic QSAR problems for proteins. In this sense, truncation approach could be
      used as in molecular dynamic to perform timely calculations. The spherical
      truncation of electrostatic field with different functions breaks down long-range
      interactions at a given cutoff distance (r(off)) resulting in short-range ones.
      Consequently, a Markov chain model may approach to the average electrostatic
      potentials of spatial distribution of charges within the protein backbone. These
      average electrostatic potentials can be used to predict proteins properties.
      Herein, we explore the effect of abrupt, shifting, force shifting, and switching
      truncation functions on 3D-QSAR models classifying 26 proteins with different
      functions: lysozymes, dihydrofolate reductases, and alcohol dehydrogenases.
      Almost all methods have shown overall accuracies higher than 73%. The present
      result points to an acceptable robustness of the MC for different truncation
      schemes and r(off) values. The results of best accuracy 92% with abrupt
      truncation coincide with our recent communication. We also developed models with
      the same accuracy value for other truncation functions; however they are more
      complex functions. PCA analysis for 152 non-homologous proteins has shown that
      there are five main eigenvalues, which explain more than 87% of the variance of
      the studied properties. The present molecular descriptors may encode structural
      information not totally accounted for the previous ones, so success with these
      descriptors could be expected when classic fails. The present result confirms the
      utility of our Markov models combined with truncation approach to generate
      bioorganic structure protein molecular descriptors for QSAR.

PMID- 15862993
TI  - Improvement of ACE inhibitory activity of chitooligosaccharides (COS) by carboxyl
      modification.
AB  - In the present research, chitooligosaccharides (COS) were carboxylated with 
      COCH(2)CH(2)COO(-) groups to obtain specific structural features similar to
      Captopril. Angiotensin I converting enzyme (ACE) inhibitory activity of
      carboxylated COS was studied and observed to enhance its activity with increased
      substitution degree. Further, Lineweaver-Burk plot analysis revealed that
      inhibition was competitive via obligatory binding site of the enzyme. This was
      accompanied with substitution of positively charged quarternized amino groups to
      COS with different substitution degrees, in which negative impact on ACE
      inhibition was observed.

PMID- 15862994
TI  - Synthesis and cytotoxic activity of N-[(alkylamino)alkyl]carboxamide derivatives
      of 7-oxo-7H-benz[de]anthracene, 7-oxo-7H-naphtho[1,2,3-de]quinoline, and 7-oxo-7H
      benzo[e]perimidine.
AB  - 7-Oxo-7H-naphtho[1,2,3-de]quinoline-11-carboxamides and analogues were prepared
      and evaluated for in vitro and in vivo antitumor activity. Chromophore variations
      included 'deaza' (7-oxo-7H-benz[de]anthracene) and 'diaza' (7-oxo-7H
      benzo[e]perimidine) analogues, and side chain variations included chiral alpha
      methyl compounds. The naphthoquinolines were the most cytotoxic, with IC(50)
      values of 5-20 nM, and showed the strongest DNA binding, with high selectivity
      for G-C rich DNA. The chiral alpha-methyl analogues were 10-20-fold more
      cytotoxic than the parent des-methyl compound. Both enantiomers provided
      substantial growth delays against s.c. colon 38 tumors in mice, with the R
      enantiomer more active than the S (tumor growth delays of >35 and 12 days,
      respectively).

PMID- 15862995
TI  - Regioselective synthesis of cyclodextrin mono-substituted conjugates of non
      steroidal anti-inflammatory drugs at C-2 secondary hydroxyl by protease in non
      aqueous media.
AB  - Three beta-cyclodextrin (beta-CD) conjugates of non-steroidal anti-inflammatory
      drugs were synthesized by enzymatic methods. Transesterification of beta-CD with
      vinyl ester of indomethacin, ketoprofen and etodolac was performed by the
      catalysis of alkaline protease from Bacillus subtilis in anhydrous DMF for 3
      days. The drug molecules were selectively conjugated onto one of the secondary
      hydroxyl groups of beta-CD through ester-linkage to improve their poor water
      solubility and absorption characteristics. The products were characterized by ESI
      MS, (1)H NMR and (13)C NMR. The structures of products with monoacylation
      occurring at the C-2 secondary hydroxyl groups of beta-CD were confirmed.

PMID- 15862996
TI  - An artificial aspartic proteinase system.
AB  - A series of aza crown ether derivatives with or without carboxyl groups in their
      side arms were synthesized and the former showed deacylation activities toward
      amino acid p-nitrophenyl ester hydrohalides. Substrate-selective phenomena were
      also observed. The relationship between the structures and deacylation activities
      of corresponding compounds suggested a nucleophilic catalytic mechanism. The
      results partially simulate some aspartic proteinases in the case of catalytic
      mechanism and are also useful for us to understand the detailed catalytic process
      of aspartic proteinases.

PMID- 15862997
TI  - Search for the pharmacophore in prazosin for Transport-P.
AB  - Partial structures of prazosin have been synthesised and tested for inhibition of
      Transport-P in order to identify the structural features of prazosin, which
      appear to be involved in binding to the putative transporter. It is shown that
      the pyrimidinyl 4-amino group is critically important for binding but that the
      6,7-dimethoxy and 2-furoyl groups are not essential.

PMID- 15862998
TI  - Comparison of positively charged DNG with DNA duplexes: a computational approach.
AB  - Molecular dynamics is used to investigate the structural properties of the
      cationic DNA analogue deoxynucleic guanidine (DNG), in which a guanidinium group
      replaces the phosphate moiety of DNA. This study examines the DNG duplex
      dodecamers d(Ag)(12).d(Tg)(12) and d(Gg)(12).d(Cg)(12), as well as their DNA
      counterparts. Watson-Crick base-pairing is maintained in the solvated DNG duplex
      models during the 5ns simulations. The idealized DNG dodecamers assume many
      parameters characteristic of the corresponding native DNA, assuming B-DNA
      conformations. Several helical parameters are rather unique to DNG, including
      buckle, slide, inclination, propeller, and X-displacement. Fewer transitions in
      backbone torsions occur in the DNG duplexes compared to those of the DNA, which
      may result from the greater rigidity of the sp(2) hybridized guanidinium group
      verses the flexible sp(3) phosphate group. The DNG helices have exceptionally
      shallow major grooves and very deep minor grooves. The major and minor groove
      widths of DNG are narrower than those of the respective DNA counterparts.

PMID- 15862999
TI  - Structure-affinity relationships of halogenated predicentrine and glaucine
      derivatives at D1 and D2 dopaminergic receptors: halogenation and D1 receptor
      selectivity.
AB  - Halogenation of the aporphine alkaloid boldine at the 3-position leads to
      increased affinity for rat brain D(1)-like dopaminergic receptors with some
      selectivity over D(2)-like receptors. A series of 3-halogenated and 3,8
      dihalogenated (halogen=Cl, Br or I) derivatives of predicentrine (9-O
      methylboldine) and glaucine (2,9-di-O-methylboldine) were prepared and assayed
      for binding at D(1) and D(2) sites. Halogenation of predicentrine led to strong
      increases in affinity for D(1)-like receptors, while the affinities for D(2)-like
      receptors were either practically unchanged or reduced three- to fourfold.
      Halogenated glaucine derivatives did not show any clear trend towards enhanced
      selectivity, and the affinities were poor and similar to or worse than the values
      previously recorded for glaucine itself. Together with earlier work on boldine
      derivatives, these results suggest that the 2-hydroxy group on the aporphine
      skeleton may determine a binding mode favoring D(1)-like over D(2)-like
      receptors, with enhanced affinity when the C-3 position is halogenated.

PMID- 15863000
TI  - 5-(3-Bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4
      ylamine: structure-activity relationships of 7-substituted heteroaryl analogs as
      non-nucleoside adenosine kinase inhibitors.
AB  - 4-Amino-5,7-disubstituted pyridopyrimidines are potent, non-nucleoside inhibitors
      of adenosine kinase (AK). We recently identified a potent, orally efficacious
      analog, 4 containing a 7-pyridylmorpholine substituted ring system as the key
      structural element of this template. In this report, we disclose the
      pharmacologic effects of five- and six-membered heterocyclic ring replacements
      for the pyridine ring in 4. These replacements were found to have interesting
      effects on in vivo efficacy and genotoxicity as well as in vitro potency. We
      discovered that the nitrogen in the heterocyclic ring at C(7) is important for
      the modulation of mutagenic side effects (Ames assay).

PMID- 15863001
TI  - A novel class of sodium/calcium exchanger inhibitor: design, synthesis, and
      structure-activity relationships of 3,4-dihydro-2(1H)-quinazolinone derivatives.
AB  - Design, synthesis, and structure-activity relationships of 3,4-dihydro-2(1H)
      quinazolinone derivatives as inhibitors of the sodium/calcium (Na(+)/Ca(2+))
      exchanger are discussed. These studies, based on a lead compound 9a, which was
      identified in our library, involved systematic modification of three regions and
      revealed that (1) the 3,4-dihydro-2(1H)-quinazolinone having a tertiary amino
      alkyl side chain at the 3-position is essential for activity, (2) a
      nonsubstituted phenyl ring is most suitable for high activity, and (3)
      introduction of a 4-substituted piperidine moiety enhanced the activity, in
      particular 4-benzylpiperidin-1-yl showed strong inhibitory activity. Based on
      these SAR studies, a structurally novel and highly potent inhibitor against the
      Na(+)/Ca(2+) exchanger, 12g (SM-15811), was discovered. In particular, SM-15811
      directly inhibited the Na(+)-dependent Ca(2+) influx via the Na(+)/Ca(2+)
      exchanger in cardiomyocytes with a high potency. The activity was almost two
      orders more potent than the lead compound 9a and SM-15811 exerted a protective
      effect against myocardial ischemic reperfusion injury. These Na(+)/Ca(2+)
      inhibitors could have a therapeutic potential for the treatment of ischemic
      reperfusion injury.

PMID- 15863002
TI  - The role of hydrophobic properties of chemicals in promoting allosteric
      reactions.
AB  - An allosteric reaction has been found in a variety of instances where an inverted
      parabolic relationship between biological activity and hydrophobicity is
      apparent, that is the activity first decreases as hydrophobicity increases and
      after a certain point, activity begins to increase. This could be attributed to
      the ligands causing a change in the receptor structure. In this report, the role
      of hydrophobic properties of chemicals in promoting allosteric reactions have
      been discussed in term of hydrophobicity (logP) by the formulation of a total
      number of 50 QSAR equations. The QSAR model of this type may be represented by
      Eq. I.

PMID- 15863003
TI  - Synthesis, in vitro, and in vivo characterization of an integrin alpha(v)beta(3)
      targeted molecular probe for optical imaging of tumor.
AB  - Integrin alpha(v)beta(3) is a widely-recognized target for the development of
      targeted molecular probes for imaging pathological conditions. alpha(v)beta(3) is
      a cell-surface receptor protein that is upregulated in various pathological
      conditions including osteoporosis, rheumatoid arthritis, macular degeneration,
      and cancer. The synthesis of an alpha(v)beta(3)-targeted optical probe 7 from
      compound 1, and its in vitro and in vivo characterization is described. A series
      of aliphatic carbamate derivatives of the potent non-peptide integrin antagonist
      1 was synthesized and the binding affinity to alpha(v)beta(3) was determined in
      both enzyme linked immunosorbent assay (ELISA) and cell adhesion inhibition
      assays. The hydrophobic carbamate-linked appendages improved the binding affinity
      of the parent compound for alpha(v)beta(3) by 2-20 times. A Boc-protected
      neopentyl derivative in the series is shown to have the best binding affinity to
      alpha(v)beta(3) (IC(50)=0.72 nM) when compared to compound 1 as well as to c
      RGDfV. Optical probe 7 utilizes the neopentyl linker and demonstrates increased
      binding affinity and significant tumor cell uptake in vitro as well as specific
      tumor accumulation and retention in vivo. These results illustrate the potential
      of employing integrin-targeted molecular probes based on 1 to image a multitude
      of diseases associated with alpha(v)beta(3) overexpression.

PMID- 15863004
TI  - Semisynthesis and biological activity of aminoacyl triesters of squamocin, an
      annonaceous acetogenin.
AB  - A number of aminoacyl triesters of squamocin 1, a cytotoxic acetogenin isolated
      from the seeds of Annona reticulata, have been synthesized in two to three steps
      from protected (l)-aminoacids and squamocin 1 using standard
      coupling/deprotection procedures. These semisynthetic analogs were tested on
      submitochondrial particles (SMP) for their complex I inhibitory activities, and
      against KB 3-1 cells in vitro. All triesters derivatives exhibited a complete
      extinction of activity at the enzymatic level, correlated to a reduced though
      modulated cytotoxicity in comparison with squamocin 1. This activity can
      apparently be considered as a function of the amphipathy of the analogs, the more
      amphiphilic ones being the more cytotoxic.

PMID- 15863005
TI  - Substrate specificity of the bovine serum amine oxidase and in situ
      characterisation of aminoaldehydes by NMR spectroscopy.
AB  - The oxidation of spermidine or homospermidine with bovine serum amine oxidase
      (BSAO) was monitored in situ, using proton nuclear magnetic resonance
      spectroscopy in water with 10% D(2)O. NMR assignments were performed by spin
      decoupling and COSY spectra or by comparison with data from synthetic
      aminoaldehydes. The results represent the first in situ characterisation of the
      highly reactive aminoaldehydes and showed oxidation at the N(1) amino group of
      spermidine and homospermidine. Comparison of homospermidine with a variety of
      substrates revealed that among straight chain di- and polyamines both an
      aminopropyl group and two primary amino groups separated by seven (norspermidine)
      or eight (spermidine) carbon atoms were required for optimal substrate ability.
      However, highest activity was seen with the substrate N-(4
      aminobutyl)hexahydropyrimidine, showing that the substrate channel of BSAO has a
      dual substrate preference, with moderately bulky substituents at the distal end
      of a diamine contributing equally well as an alkyl amino group. Cytotoxic
      investigations of a variety of substrates for BSAO, confirmed previous results,
      that cytotoxicity is primarily linked to polyamines encompassing the aminopropyl
      moiety. No acrolein was observed at any time during the oxidation showing that it
      reacts very fast with available amino groups forming a variety of derivatives.

PMID- 15863006
TI  - Antimycobacterial activity of new 3-substituted 5-(pyridin-4-yl)-3H-1,3,4
      oxadiazol-2-one and 2-thione derivatives. Preliminary molecular modeling
      investigations.
AB  - 3H-1,3,4-Oxadiazole-2-thione and 3H-1,3,4-oxadiazol-2-one derivatives were
      synthesized and tested for their in vitro antimycobacterial activity.
      Oxadiazolone derivatives showed an interesting antimycobacterial activity against
      the tested strain of Mycobacterium tuberculosis H(37)Rv, whereas the
      corresponding thione derivatives were devoid of activity. Molecular modeling
      investigations showed that the active compounds may interact at the active site
      of the mycobacterial cytochrome P450-dependent sterol 14alpha-demethylase in the
      sterol biosynthesis pathway and that their binding free energy values are in
      agreement with their MIC values.

PMID- 15863007
TI  - Anti-oxidant activities of curcumin and related enones.
AB  - The natural product curcumin (diferuloylmethane, 1,7-bis(4-hydroxy-3
      methoxyphenyl)-1,6-heptadiene-3,5-dione), obtained from the spice turmeric,
      exhibits numerous biological activities including anti-cancer, anti-inflammatory,
      and anti-angiogenesis activities. Some of these biological activities may derive
      from its anti-oxidant properties. There are conflicting reports concerning the
      structural/electronic basis of the anti-oxidant activity of curcumin. Curcumin is
      a symmetrical diphenolic dienone. A series of enone analogues of curcumin were
      synthesized that included: (1) curcumin analogues that retained the 7-carbon
      spacer between the aryl rings; (2) curcumin analogues with a 5-carbon spacer; and
      (3) curcumin analogues with a 3-carbon spacer (chalcones). These series included
      members that retained or were devoid of phenolic groups. Anti-oxidant activities
      were determined by the TRAP assay and the FRAP assay. Most of the analogues with
      anti-oxidant activity retained the phenolic ring substituents similar to
      curcumin. However, a number of analogues devoid of phenolic substituents were
      also active; these non-phenolic analogues are capable of forming stable tertiary
      carbon-centered radicals.

PMID- 15863008
TI  - Investigation into the structure-activity relationship of novel concentration
      dependent, dual action T-type calcium channel agonists/antagonists.
AB  - This paper describes the synthesis and biological evaluation of a series of
      straight chain analogs of a compound (1) that was previously synthesized in our
      research program. These compounds, which are T-type calcium channel antagonists,
      exhibits potent anti-proliferative activity against a variety of cancer cells. A
      structure-activity relationship of these analogs against a variety of cancer
      cells has provided insight into a logical pharmacophore for this series of
      compounds. Furthermore, this series of compounds has presented itself as a set of
      novel, concentration dependent, dual action agonists/antagonists for the T-type
      calcium channel.

PMID- 15863009
TI  - Mechanism of proliferation arrest of embryonic cells of Xenopus by diterpene
      compounds.
AB  - Three diterpene compounds isolated from the anti-cancer herbal medicine kansui,
      namely, kansuinin B, 20-OD-ingenol Z, and 20-OD-ingenol E, specifically inhibited
      the proliferation of isolated embryonic cells from Xenopus embryos. We conducted
      a cytologic study to determine the mechanism underlying the arrest of the
      cellular proliferation by these compounds. While kansuinin B and 20-OD-ingenol Z
      treatment decreased the cell numbers in the S phase and the M phase substages of
      the cell cycle, 20-OD-ingenol E inhibited mitosis.

PMID- 15863010
TI  - New antitubulin derivatives in the combretastatin A4 series: synthesis and
      biological evaluation.
AB  - Two series of combretastatin A4 derivatives (acrylamide=carboxamide and
      carbamate) were synthesized in order to improve the water solubility and
      stabilize the cis-configuration of the double bond. Their cytotoxic effects were
      evaluated against MCF-7, KB-3-1 and IGROV human cancer cell lines, as well as
      their inhibitory activity on tubulin polymerization. Results were compared to
      those of carboxamide 1, chosen as reference. Potent inhibitions were observed on
      both tests in the carboxamide series, particularly for compound 4d bearing a
      fluorine group in replacement of the 3-hydroxyl of CA4. In contrast, most of the
      carbamates were either inactive or displayed only moderate cytotoxicities.
      Interestingly, a submicromolar IC(50) was measured on MCF-7 cells for 6g,
      although this compound was totally devoid of antitubulin activity.

PMID- 15863011
TI  - Administration of yeast glucan enhances survival and some non-specific and
      specific immune parameters in carp (Cyprinus carpio) infected with Aeromonas
      hydrophila.
AB  - Effects of beta-glucan administration on survival and immune modulations were
      studied in Cyprinus carpio against the bacterial pathogen, Aeromonas hydrophila.
      Beta-glucan was extracted from Saccharomyces cervisiae and purified. A virulent
      strain of the pathogen A. hydrophila was collected from infected fish. Different
      concentrations of beta-glucan were administered to test animals on day 1, 3 and 5
      through different routes (intraperitoneal injection (ip), bathing and oral
      administration). Control and test animals were challenged by ip injection of LD50
      concentration of A. hydrophila on day 7 and mortality was observed and Relative
      Percent Survival (RPS) was calculated. Intraperitoneal injection of 500 microg of
      glucan significantly enhanced the RPS; bathing and oral administration of glucan
      did not influence the RPS. On day 7, test animals injected with 100, 500 and 1000
      microg of glucan had a significant increase in total blood leucocyte counts and
      an increase in the proportion of neutrophils and monocytes. Superoxide anion
      production by kidney macrophages was also elevated. RT-PCR and northern blot
      analysis of interleukin-1 mRNA showed elevated expression in kidney on day 7 in
      fish injected with glucan. Glucan had an adjuvant effect on antibody production
      as pretreatment by injection of 100-1000 microg glucan/fish resulted in the
      highest antibody titer against A. hydrophila following vaccination. Classical and
      alternative complement pathways were not affected by glucan administration by any
      of the three routes.

PMID- 15863012
TI  - Effects of cyclophosphamide on the immune system and disease resistance of Asian
      catfish Clarias batrachus.
AB  - Cyclophosphamide (CYP), a multifunctional alkylating agent is known as a potent
      immunosuppressor in endotherms. Here, an experiment was conducted in an
      ectothermic Asian catfish species, Clarias batrachus to investigate its effect on
      non-specific and specific immunity as well as disease resistance against a common
      bacterial pathogen challenge. CYP was intraperitoneally injected for 3
      consecutive days at a rate of 200 mgkg(-1) body weight. After 72 h post
      injection, control and CYP-treated fish were screened for superoxide production
      through nitroblue tetrazolium (NBT) assay, myeloperoxidase (MPO) activity, packed
      cell volume (PCV) and total protein, lysozyme, alternative complement activity
      (ACH50) and natural haemagglutinin titre as a measure of non-specific immunity
      level as well as disease resistance against Aeromonas hydrophila challenge to
      vaccinated and unvaccinated fish. To study the effect on specific immunity, CYP
      was injected thrice at an interval of 7 days after bacterin injection and serum
      antibody titre was measured by bacterial agglutination titre assay. The results
      showed a significant (P<0.05) decrease in NBT and MPO activities, and percent
      survival against A. hydrophila challenge (both in unvaccinated and vaccinated
      fish) in CYP-treated fish, when compared to control fish. The above results
      support the immunosuppressive action of CYP in freshwater catfish, C. batrachus.
      The neutrophil activities, as measured through superoxide production and
      myeloperoxidase levels, might be important contributors during A. hydrophila
      infection and that treatment with CYP reduces phagocytic killing power and
      inhibits resistance against aeromoniasis.

PMID- 15863013
TI  - Molecular cloning and response to laminarin stimulation of arginine kinase in
      haemolymph in Chinese shrimp, Fenneropenaeus chinensis.
AB  - Arginine kinase (AK) was previously reported as a phosphagen-ATP
      phosphotransferase found in invertebrates. In this study, an 1184 bp cDNA was
      cloned and sequenced. It contained an open reading frame of 1068 bp that coded
      for 356 deduced amino acids of AK in Fenneropenaeus chinensis. The calculated
      molecular mass of AK is 40129.73 Da and pI is 5.92. The predicted protein showed
      a high level of identity to known AK in invertebrates and creatine kinase from
      vertebrates, which belong to a conserved family of ATP:guanidino phospho
      transferases. In addition, AK protein in plasma of F. chinensis was identified
      using two-dimensional electrophoresis (2DE) and electrospray ionization mass
      spectrometry (ESI-MS) according to the calculated molecular mass and pI. AK was
      significantly decreased in the plasma of F. chinensis at 45 min and recovered at
      3 h after laminarin injection as confirmed by 2DE and ESI-MS. The results showed
      that AK was one of the most significantly changed proteins on two-dimensional gel
      in the plasma proteins of F. chinensis at 45 min and 3 h after simulation.

PMID- 15863014
TI  - Effect of dietary carbohydrate on haematology, respiratory burst activity and
      histological changes in L. rohita juveniles.
AB  - A feeding trial was conducted for 60 days to delineate the effect of dietary
      carbohydrate on the haematology, respiratory burst activity and histology in
      Labeo rohita juveniles. One hundred and forty four fish (av. wt. 10+/-0.15 g)
      were randomly distributed into 12 treatment groups with each of two replicates.
      Twelve semi-purified diets with either 35% or 28% of crude protein were prepared
      with different amylase concentrations (0, 50, 100 and 150 mgkg(-1)) and starch
      type (gelatinised, G/non-gelatinised, NG) designated as T1 (NG, 35% CP, 0 mgkg(
      1) amylase), T2 (G, 35% CP, 0 mgkg(-1) amylase), T3 (NG, 28% CP, 50 mgkg(-1)
      amylase), T4 (NG, 35% CP, 50 mgkg(-1) amylase), T5 (G, 28% CP, 50 mgkg(-1)
      amylase), T6 (G, 35% CP, 50 mgkg(-1) amylase), T7 (NG, 28% CP, 100 mgkg(-1)
      amylase), T8 (NG, 35% CP, 100 mgkg(-1) amylase), T9 (G, 28% CP, 100 mgkg(-1)
      amylase), T10 (G, 35% CP, 100 mgkg(-1) amylase), T11 (NG, 28% CP, 150 mgkg(-1)
      amylase) and T12 (NG, 35% CP, 150 mgkg(-1) amylase). The fish were acclimatised
      to the experimental conditions for 15 days during which time the control diet was
      fed. The blood haemoglobin percentage and RBC count was not significantly
      different (P>0.05) among the various treatments. Highest WBC count, total plasma
      protein, serum globulin and respiratory burst activity was found at 50 mgkg(-1)
      dietary amylase supplementation, whereas no variation (P>0.05) was found at 0,
      100 and 150 mgkg(-1) dietary amylase supplementation. There was no difference
      (P>0.05) in the serum albumin and AG ratio among the experimental groups. Feeding
      either gelatinised or non-gelatinised carbohydrate did not affect the
      histological structure of the liver, kidney and intestine except in the T4 and T7
      groups. The T4 group showed hyperplasia of the intestine and moderate vacuolation
      in hepatic cells, whereas the T7 group showed hyperplasia of the intestine. Non
      gelatinised carbohydrates (46%) along with supplementation with 50 mgkg(-1)
      amylase stimulated the immune system in L. rohita juveniles. But supplementation
      of amylase to the gelatinised carbohydrate had no immunostimulating effect.

PMID- 15863015
TI  - The effect of sea bream (Sparus aurata) broodstock and larval vaccination on the
      susceptibility by Photobacterium damsela subsp. piscicida and on the humoral
      immune parameters.
AB  - Sea bream broodstock were immunised 1 or 2 months before spawning with a novel
      photobacteriosis vaccine. Sixty-seven-day-old larvae (mean weight 22.3 mg)
      originating from immunised and non-immunised parents were experimentally infected
      with the Photobacterium damsela subsp. piscicida (Phdp). Larvae from immunised
      fish showed delayed onset and lower mortality (66.67%) compared with larvae from
      control fish (80%). Eighty-nine-day-old larvae (mean weight 162.2 mg) from both
      groups were bath vaccinated with Phdp and Escherichia coli lipopolysaccharides
      (LPS) and larval samples were collected for measurement of humoral parameters.
      Larvae vaccinated with Phdp and LPS showed significantly higher anti-protease
      activity, lysozyme activity and total immunoglobulin compared to the controls.
      One-hundred-and-twenty-day-old larvae (mean weight 297.85 mg) from both parental
      groups were challenged with (LD70) virulent Phdp bacterial cells. Vaccinated
      larvae from both groups showed significantly less mortality compared to the
      respective controls. The RPS values of larvae from immunised parents vaccinated
      with Phdp and LPS was 95.83% and 72.22%, respectively. The RPS values of larvae
      from non-immunised parents vaccinated with Phdp and LPS was 62.5% and 70.83%,
      respectively. Results are discussed with respect to the beneficial effect of
      broodstock immunisation prior to spawning and the immunisation of larvae on their
      survival against photobacteriosis.

PMID- 15863016
TI  - Comparison of respiratory burst activity of inflammatory neutrophils in ayu
      (Plecoglossus altivelis) and carp (Cyprinus carpio).
AB  - Neutrophils of ayu (Plecoglossus altivelis) were previously shown to have
      unusually high respiratory burst activity (RBA). To understand this unique
      character of ayu neutrophils, the RBAs of resting and inflammatory neutrophils of
      ayu and carp (Cyprinus carpio) were compared. Inflammation was induced in the
      peritoneal cavity by injecting killed-bacteria. The RBA of peritoneal-exudate
      (inflammatory) neutrophils was measured after stimulation with phorbol myristate
      acetate (PMA). Resting neutrophils were obtained from kidney and blood of non
      injected fish. In carp, the RBA of inflammatory neutrophils was much higher than
      that of resting neutrophils. On the other hand, in ayu no significant difference
      was observed. The RBA of neutrophils was already high in the kidney stock. The
      process of inflammation did not further enhance RBA. In addition to PMA, other
      stimulants (zymosan, opsonized-zymosan, and zymosan-treated serum) were used to
      measure RBA. Even with these stimulants, the RBA of inflammatory neutrophils was
      always higher than that of kidney neutrophils in carp. On the other hand in ayu,
      the RBA of kidney neutrophils was already high in the kidney stock, and no
      significant difference was observed between peritoneal and kidney neutrophils in
      ayu. These results indicate ayu neutrophils have spontaneously activated
      characteristics with the respect to the ROS generation in the kidney
      hematopoietic-stock.

PMID- 15863017
TI  - Effects of dopamine on the immunity of white shrimp Litopenaeus vannamei.
AB  - The total haemocyte count (THC), phenoloxidase activity, respiratory burst,
      superoxide dismutase (SOD) activity, phagocytic activity and clearance efficiency
      in response to pathogen Vibrio alginolyticus were measured when the white shrimp
      Litopenaeus vannamei (20.0+/-1.5 g) were injected individually with dopamine at
      10(-8), 10(-7) and 10(-6)mol shrimp(-1), respectively. For the shrimp that
      received dopamine at 10(-7) and 10(-6)mol shrimp(-1), the THC decreased by 25%
      and 39%, phenoloxidase activity decreased by 15% and 32%, respiratory burst
      decreased by 21% and 36%, and SOD activity decreased by 50% and 63%,
      respectively, after 4 h. The phagocytic activity and clearance efficiency of
      shrimp that received dopamine at either dose decreased significantly after 2 h.
      The THC, phenoloxidase activity, respiratory burst, SOD activity, phagocytic
      activity and clearance efficiency returned to normal values after 16, 8, 8, 24,
      16 and 4 h, respectively, for the shrimp that received dopamine at either dose.
      In another experiment, L. vannamei which had received dopamine at 10(-8), 10(-7)
      and 10(-6)mol shrimp(-1) were challenged after 1 h by injection with V.
      alginolyticus at 1.0x10(5) colony-forming units (cfu) shrimp-1 and then placed in
      seawater of 20 per thousand. The cumulative mortality of shrimp that received
      dopamine at either dose was significantly higher than that of shrimp that
      received saline after 8 h, and of shrimp that received saline at the termination
      of the experiment (48 h after the challenge). It is therefore concluded that
      dopamine administration at 10(-6)mol shrimp-1 or less causes immune modulation of
      L. vannamei.

PMID- 15863018
TI  - Transferrin and antiproteases are major proteins of common carp seminal plasma.

PMID- 15863019
TI  - Forensic examination of suspected child victims of sexual abuse in the UK: a
      personal view.
AB  - Expert opinion in child abuse has received considerable bad press and currently
      public confidence in this area of medical practice is low. Media interest has
      focused most on the diagnosis of factitious illness. However doctors who examine
      children in respect of proceedings arising from suspected sexual abuse should be
      mindful this area is potentially just as problematic. Widely different rates of
      abnormal findings have been reported. At least in part this has reflected
      inconsistency in interpretation. Findings once assumed diagnostic of penetration
      are now recognised to occur in non-abused children. The practical difficulties of
      examining a reluctant child and achieving adequate visualisation of the hymen in
      relaxed state, are frequently underestimated. Where normal or non-specific
      findings are presented as "consistent with the alleged event" there is a high
      risk the court will perceive them to be significant. Guidelines have tended to
      lag behind existing knowledge and made inadequate differentiation between
      prepubertal and adolescent cases. They have also placed a high degree of reliance
      on statements from children without regard to the context in which any
      "disclosure" had arisen. Photodocumentation has important benefits, and
      limitations. Images may not display the true depth of field and are not the same
      as examining the child directly. Examination must remain the gold standard. There
      is a moral duty of care on the examining doctor to understand and clarify the
      status of findings dispassionately and with due regard to the level of the
      evidence base.

PMID- 15863020
TI  - Triage in trauma-care system: a forensic view.
AB  - Trauma is a significant cause of death and suffering in society and there is
      strong evidence that mortality and morbidity may be reduced by provision of
      effective medical care through a trauma care system. It is reasonable to believe
      that severely injured patients should be transported as quickly as possible to a
      center where definitive medical care is possible. Conversely, it is also an
      argument that the resources of a trauma center must not be overwhelmed by
      assessment and treatment of minor trauma for patients who could be reasonably
      expected to do well with care in a clinic or a primary care hospital. Triage was
      developed to sort out those most likely to survive and to need medical care. Many
      triage tools have been developed and evaluated. However, the goal in setting
      triage criteria to provide a protocol for properly categorising injured patients,
      transporting them to appropriate hospitals, and ensuring an appropriate response
      to all trauma patients is yet to be achieved. Whatever the reasons and rate of
      failure due to different reasons, it is not unusual to read the reports wherein
      the quality of care becomes suspect in an increasingly litigious society. This
      paper examines the evolution of triage systems in trauma care from a forensic
      viewpoint.

PMID- 15863021
TI  - RAPD & FINS (mitochondrial 16s rRNA gene sequence) in analysis of food
      contamination: detection of food poisoning by Lizard.
AB  - In poisoning, detection of the nature of causative agent is important for
      management of trauma and forensic investigation. Most of the methods in clinical
      toxicology are developed for detection of toxins and poisons. A random amplified
      polymorphic DNA (RAPD)-based method has been described for detection of species
      of animal from its morphologically unrecognizable fragments, recovered from food
      substances, consumption of which caused even death. Pre-mixed RAPD reaction beads
      and six RAPD primers were used in polymerase chain reaction analysis. Among six
      RAPD primers used, any one of them was sufficient in resolving this practical
      forensic situation. To enhance the probability values for matching in the present
      study of fixing identity of an animal, six set of market available RAPD primers
      were used. This is the first report of a forensic application of RAPD DNA typing
      in identification of charred skeleton remnants of Lizard species in food
      material. Furthermore unique amplicons were generated for different reptilian
      species, which can be used as species specific markers for species identification
      in forensic situation, however, no variations among individuals of same species
      were observed.

PMID- 15863022
TI  - Forensic medicine services in Uganda--present and future.
AB  - Forensic medicine services (medico-legal services) as it is provided today in
      Uganda is discussed with special reference to forensic pathology and also to
      future plans for improvement to ensure quality service. Forensic medicine
      services are divided into clinical forensic medicine and forensic pathology. In
      Uganda, these services are rendered partly by pathologists attached to
      University, by pathologists and medical officers employed by police and by
      medical officers attached to hospitals. In Uganda, all types of unnatural deaths
      are reported to nearest police station and appointed investigating police
      officer(s) will take necessary action to have a medico-legal postmortem done as
      soon as possible. Currently there is no qualified forensic pathologist in Uganda.
      Suggestions are made with regard to the enactment of a Forensic Medicine Services
      Act by the Department of Health, the creation of a forensic medicine unit with,
      under the administrative umbrella of pathology department, in medical schools and
      imparting of forensic medicine training to anatomical pathologists to act as a
      qualified, specialist forensic pathologists.

PMID- 15863023
TI  - A case of a death by explosives: the keys to a proper investigation.
AB  - Suicidal deaths involving an explosive, unrelated to a terrorist act, are rare.
      The rarity of such events presents a unique environment for those investigating
      such a death. We report a case of suicide involving a 29-year-old white male who
      detonated a firework in his mouth, resulting in massive craniocerebral
      destruction. He was discovered in his residence shortly after the explosion.
      Initially, the case was believed to be a fatal gunshot wound by the paramedics
      and homicide detectives at the scene. Several small pieces of red colored paper
      and a possible end cap were located throughout the scene. Analysis of the paper
      and end cap showed trace components consistent with flash powder. The victim had
      used a pyrotechnic device to commit suicide. Therefore, it is critical for those
      who investigate deaths be able to identify cases that involve explosives in order
      to properly collect and analyze the evidence.

PMID- 15863024
TI  - Femoral and tibial fractures in a child with myelomeningocele.
AB  - Femoral and tibial fractures can occur from accidents, child abuse or
      pathological causes. It is often very difficult to distinguish the cause among
      those cases. Radiological diagnosis may be needed for clinicians and medical
      examiners in order to assist determining the reason of fractures. In this report,
      we submit a case with femoral and tibial fractures associated with
      myelomeningocele. This patient was diagnosed as child abuse by clinicians. On
      review it was decided that her fractures were not because of non-accidental
      injury. The values of bone mineral density of the upper limb were low and illness
      caused her fractures.

PMID- 15863025
TI  - Sexual assault of a postmenopausal woman.
AB  - Postmenopausal women account for small numbers of presentations to sexual assault
      services. Knowledge of genital anatomical and physiological changes in this
      population is essential in order to correctly interpret injuries. A case of a
      postmenopausal victim is described and discussed which illustrates some issues
      peculiar to older female victims.

PMID- 15863027
TI  - Citrate-preserved samples.

PMID- 15863029
TI  - Structural basis for fibroblast growth factor receptor activation.
AB  - FGF signaling plays a ubiquitous role in human biology as a regulator of
      embryonic development, homeostasis and regenerative processes. In addition,
      aberrant FGF signaling leads to diverse human pathologies including skeletal,
      olfactory, and metabolic disorders as well as cancer. FGFs execute their
      pleiotropic biological actions by binding, dimerizing and activating cell surface
      FGF receptors (FGFRs). Proper regulation of FGF-FGFR binding specificity is
      essential for the regulation of FGF signaling and is achieved through primary
      sequence variations among the 18 FGFs and seven FGFRs. The severity of human
      skeletal syndromes arising from mutations that violate FGF-FGFR specificity is a
      testament to the importance of maintaining precision in FGF-FGFR specificity. The
      discovery that heparin/heparan sulfate (HS) proteoglycans are required for FGF
      signaling led to numerous models for FGFR dimerization and heralded one of the
      most controversial issues in FGF signaling. Recent crystallographic analyses have
      led to two fundamentally different models for FGFR dimerization. These models
      differ in both the stoichiometry and minimal length of heparin required for
      dimerization, the quaternary arrangement of FGF, FGFR and heparin in the dimer,
      and in the mechanism of 1:1 FGF-FGFR recognition and specificity. In this review,
      we provide an overview of recent structural and biochemical studies used to
      differentiate between the two crystallographic models. Interestingly, the
      structural and biophysical analyses of naturally occurring pathogenic FGFR
      mutations have provided the most compelling and unbiased evidences for the
      correct mechanisms for FGF-FGFR dimerization and binding specificity. The
      structural analyses of different FGF-FGFR complexes have also shed light on the
      intricate mechanisms determining FGF-FGFR binding specificity and promiscuity and
      also provide a plausible explanation for the molecular basis of a large number
      craniosynostosis mutations.

PMID- 15863030
TI  - Cellular signaling by fibroblast growth factor receptors.
AB  - The 22 members of the fibroblast growth factor (FGF) family of growth factors
      mediate their cellular responses by binding to and activating the different
      isoforms encoded by the four receptor tyrosine kinases (RTKs) designated FGFR1,
      FGFR2, FGFR3 and FGFR4. Unlike other growth factors, FGFs act in concert with
      heparin or heparan sulfate proteoglycan (HSPG) to activate FGFRs and to induce
      the pleiotropic responses that lead to the variety of cellular responses induced
      by this large family of growth factors. A variety of human skeletal dysplasias
      have been linked to specific point mutations in FGFR1, FGFR2 and FGFR3 leading to
      severe impairment in cranial, digital and skeletal development. Gain of function
      mutations in FGFRs were also identified in a variety of human cancers such as
      myeloproliferative syndromes, lymphomas, prostate and breast cancers as well as
      other malignant diseases. The binding of FGF and HSPG to the extracellular ligand
      domain of FGFR induces receptor dimerization, activation and autophosphorylation
      of multiple tyrosine residues in the cytoplasmic domain of the receptor molecule.
      A variety of signaling proteins are phosphorylated in response to FGF stimulation
      including Shc, phospholipase-Cgamma, STAT1, Gab1 and FRS2alpha leading to
      stimulation of intracellular signaling pathways that control cell proliferation,
      cell differentiation, cell migration, cell survival and cell shape. The docking
      proteins FRS2alpha and FRS2beta are major mediators of the Ras/MAPK and PI-3
      kinase/Akt signaling pathways as well as negative feedback mechanisms that fine
      tune the signal that is initiated at the cell surface following FGFR stimulation.

PMID- 15863031
TI  - FGF signaling in flies and worms: more and more relevant to vertebrate biology.
AB  - FGF signaling in the invertebrate model systems Drosophila melanogaster and
      Caenorhabditis elegans was initially most obviously involved in cell motility
      events. More recently, however, FGFs and FGF signaling in these systems have been
      shown to affect many additional cellular processes. This recent work has shown
      that the pleiotropies of these FGF receptors resemble those of their vertebrate
      counterparts, and, in many cases, serve as excellent models for understanding the
      fundamental molecular mechanisms controlling these events.

PMID- 15863032
TI  - Fibroblast growth factor/fibroblast growth factor receptor system in
      angiogenesis.
AB  - Fibroblast growth factors (FGFs) are a family of heparin-binding growth factors.
      FGFs exert their pro-angiogenic activity by interacting with various endothelial
      cell surface receptors, including tyrosine kinase receptors, heparan-sulfate
      proteoglycans, and integrins. Their activity is modulated by a variety of free
      and extracellular matrix-associated molecules. Also, the cross-talk among FGFs,
      vascular endothelial growth factors (VEGFs), and inflammatory
      cytokines/chemokines may play a role in the modulation of blood vessel growth in
      different pathological conditions, including cancer. Indeed, several experimental
      evidences point to a role for FGFs in tumor growth and angiogenesis. This review
      will focus on the relevance of the FGF/FGF receptor system in adult angiogenesis
      and its contribution to tumor vascularization.

PMID- 15863033
TI  - Fibroblast growth factor signaling in tumorigenesis.
AB  - Fibroblast growth factors and their signaling receptors have been associated with
      multiple biological activities, including proliferation, differentiation and
      motility. Consequently, they have evoked interest as candidate oncogenes with the
      potential to initiate and/or promote tumorigenesis. This has resulted in a large
      literature describing the presence of these growth factors and their receptors in
      cancer cell lines and primary tumors of diverse origin. However, it is only
      recently that compelling evidence has emerged to implicate the fibroblast growth
      factors (Fgfs) and their receptors in the genesis of human cancers. Here, we
      outline the model systems that demonstrate the potential oncogenic nature of Fgf
      signaling and summarise recent evidence that implicates aberrant Fgf signaling as
      important in the natural history of some common human cancers.

PMID- 15863034
TI  - Bad bones, absent smell, selfish testes: the pleiotropic consequences of human
      FGF receptor mutations.
AB  - The discovery in 1994 that highly specific mutations of fibroblast growth factor
      (FGF) receptor 3 caused the most common form of human short-limbed dwarfism,
      achondroplasia, heralded a new era in FGF receptor (FGFR) biology. A decade
      later, the purpose of this review is to survey how the study of humans with FGFR
      mutations continues to provide insights into FGFR function in health and disease,
      and the clinical applications of these findings. Amongst the most interesting
      recent discoveries have been the description of novel phenotypes associated with
      FGFR1 and FGFR3 mutations; identification of fundamental differences in the
      cellular mechanisms of mutant FGFR2 and FGFR3 action; and the direct
      identification of FGFR2 and FGFR3 mutations in sperm. These clinical observations
      illustrate the pleiotropism of FGFR action and fuel ongoing efforts to understand
      the rich biology and pathophysiology of the FGF signalling system.

PMID- 15863036
TI  - Fibroblast growth factor homologous factors: evolution, structure, and function.
AB  - Fibroblast growth factor homologous factors (FHFs) bear strong sequence and
      structural similarity to fibroblast growth factors (FGFs). However, the
      biochemical and functional properties of FHFs are largely, if not totally,
      unrelated to those of FGFs. Whereas FGFs function through binding to the
      extracellular domains of FGF receptors (FGFRs), FHFs bind to intracellular
      domains of voltage-gated sodium channels (VGSCs) and to a neuronal MAP kinase
      scaffold protein, islet-brain-2 (IB2). These findings demonstrate the remarkable
      functional adaptability during evolution of the FGF gene family. FHF gene
      mutations in mice result in a range of neurological abnormalities, and at least
      one of these anomalies, cerebellar ataxia, is linked to FHF mutations in humans.
      This article reviews the sequences and structure of FHFs, along with our still
      limited understanding of FHF function.

PMID- 15863035
TI  - FGF signaling in the developing endochondral skeleton.
AB  - Mutations in fibroblast growth factor receptors (Fgfrs) are the etiology of many
      craniosynostosis and chondrodysplasia syndromes in humans. The phenotypes
      associated with these human syndromes and the phenotypes resulting from targeted
      mutagenesis in the mouse have defined essential roles for FGF signaling in both
      endochondral and intramembranous bone development. In this review, I will focus
      on the role of FGF signaling in chondrocytes and osteoblasts and how FGFs
      regulate the growth and development of endochondral bone.

PMID- 15863037
TI  - FGF23 and disorders of phosphate homeostasis.
AB  - It is well known that fibroblast growth factor (FGF) family members are
      associated with embryonic development and are critical for basic metabolic
      functions. This review will focus upon fibroblast growth factor-23 (FGF23) and
      its roles in disorders associated with phosphate handling. The discovery that
      mutations in FGF23 were responsible for the isolated renal phosphate wasting
      disorder autosomal dominant hypophosphatemic rickets (ADHR) has ascribed novel
      functions to the FGF family. FGF23 circulates in the bloodstream, and animal
      models demonstrate that FGF23 controls phosphate and Vitamin D homeostasis
      through the regulation of specific renal proteins. The ADHR mutations in FGF23
      produce a protein species less susceptible to proteolytic processing. X-linked
      hypophosphatemic rickets (XLH), tumor-induced osteomalacia (TIO), and fibrous
      dysplasia of bone (FD) are disorders involving phosphate homeostasis that share
      phenotypes with ADHR, indicating that FGF23 may be a common denominator for the
      pathophysiology of these syndromes. Our understanding of FGF23 will help to
      develop novel therapies for phosphate wasting disorders, as well as for disorders
      of increased serum phosphate, such as tumoral calcinosis, a rare disorder, and
      renal failure, a common disorder.

PMID- 15863038
TI  - Mechanisms underlying differential responses to FGF signaling.
AB  - Fibroblast growth factors (FGFs) are key regulators of several developmental
      processes in which cell fate and differentiation to various tissue lineages are
      determined. The importance of the proper spatial and temporal regulation of FGF
      signals is evident from human and mouse genetic studies which show that mutations
      leading to the dysregulation of FGF signals cause a variety of developmental
      disorders including dominant skeletal diseases and cancer. The FGF ligands signal
      via a family of receptor tyrosine kinases and, depending on the cell type or
      stage of maturation, produce diverse biological responses that include
      proliferation, growth arrest, differentiation or apoptosis. A central issue in
      FGF biology is to understand how these diverse cellular responses are determined
      and how similar signaling inputs can generate distinct patterns of gene
      expression that govern the specificity of the cellular response. In this review
      we draw upon studies from the past fifteen years and attempt to construct a
      molecular picture of the different levels of regulation by which such specific
      cellular responses could be achieved by FGF signals. We discuss whether
      specificity could lie in the nature of the ligand, the particular receptor, the
      signal transduction pathways utilized, or the transcriptional regulation of
      specific genes. Finally, we also discuss how the interplay of FGF signals with
      other signaling systems could contribute to the cellular response. In particular
      we focus on the interaction with the Wnt pathway since FGF/Wnt cross-talk is
      emerging as an important nexus in regulating a variety of biological processes.

PMID- 15863039
TI  - Spectroscopic study of protoporphyrin IX zinc(II) encapsulated in sol-gel glass.
AB  - Previous studies indicated that the organization of native porphyrins and their
      intentionally designated derivatives in solid substrates is of current interest
      because of the biological and practical importance of these compounds. In this
      paper, we report herein for the first time the incorporation of a functionalized
      diacid, protoporphyrin IX Zn(II) (Zn-pp-IX), successfully in a silica based
      transparent organic-inorganic hybrid material by choosing proper alkoxy silane
      containing amino-group via the sol-gel method. The entrapped guest was diagnosed
      using UV-vis sectrophotometry, emission spectroscopy, and infrared spectrometry;
      the properties of the encapsulated porphyrin were compared to those of the
      compound in solution. The results indicate that Zn-pp-IX is well distributed and
      homogeneously in the glass.

PMID- 15863040
TI  - Spectroscopic characterization of chromite from the Moa-Baracoa Ophiolitic
      Massif, Cuba.
AB  - The Cuban chromites with a spinel structure, FeCr2O4 have been studied using
      optical absorption and EPR spectroscopy. The spectral features in the electronic
      spectra are used to map the octahedral and tetrahedral co-ordinated cations.
      Bands due Cr3+ and Fe3+ ions could be distinguished from UV-vis spectrum.
      Chromite spectrum shows two spin allowed bands at 17,390 and 23,810 cm(-1) due to
      Cr3+ in octahedral field and they are assigned to 4A2g(F) --> 4T2g(F) and 4A2g(F)
      --> 4T1g(F) transitions. This is in conformity with the broad resonance of Cr3+
      observed from EPR spectrum at g = 1.903 and a weak signal at g = 3.861 confirms
      Fe3+ impurity in the mineral. Bands of Fe3+ ion in the optical spectrum at
      13,700, 18,870 and 28,570 cm(-1) are attributed to 6A1g(S) --> 4T1g(G), 6A1g(S) -
      > 4T2g(G) and 6A1g(S) --> 4T2g(P) transitions, respectively. Near-IR reflectance
      spectroscopy has been used effectively to show intense absorption bands caused by
      electronic spin allowed d-d transitions of Fe2+ in tetrahedral symmetry, in the
      region 5000-4000 cm(-1). The high frequency region (7500-6500 cm(-1)) is
      attributed to the overtones of hydroxyl stretching modes. Correlation between
      Raman spectral features and mineral chemistry are used to interpret the Raman
      data. The Raman spectrum of chromite shows three bands in the CrO stretching
      region at 730, 560 and 445 cm(-1). The most intense peak at 730 cm(-1) is
      identified as symmetric stretching vibrational mode, A1g(nu1) and the other two
      minor peaks at 560 and 445 cm(-1) are assigned to F2g(nu4) and E(g)(nu2) modes,
      respectively. Cation substitution in chromite results various changes both in
      Raman and IR spectra. In the low-wavenumber region of Raman spectrum a
      significant band at 250 cm(-1) with a component at 218 cm(-1) is attributed
      F2g(nu3) mode. The minor peaks at 195, 175, 160 cm(-1) might be due to E(g) and
      F2g symmetries. Broadening of the peak of A1g mode and shifting of the peak to
      higher wavenumber observed as a result of increasing the proportion of Al3+O6.
      The presence of water in the mineral shows bands in the IR spectrum at 3550,
      3425, 3295, 1630 and 1455 cm(-1). The vibrational spectrum of chromite gives
      raise to four frequencies at 985, 770, 710 and 650 cm(-1). The first two
      frequencies nu1 and nu2 are related to the lattice vibrations of octahedral
      groups. Due to the influence of tetrahedral bivalent cation, vibrational
      interactions occur between nu3 and nu4 and hence the low frequency bands, nu3 and
      nu4 correspond to complex vibrations involving both octahedral and tetrahedral
      cations simultaneously. Cr3+ in Cuban natural chromites has highest CFSE (20,868
      cm(-1)) when compared to other oxide minerals.

PMID- 15863041
TI  - Interaction of 2,3-dichloro-1,4-naphthoquinone with n-butylamine in halocarbon
      solvents.
AB  - The rapid interaction between 2,3-dichloro-1,4-naphthoquinone (DClNQ) and n
      butylamine results in the formation of 2N(n-butylamino)-3-chloro-1,4
      naphthoquinone as the final product. The reaction is found to proceed through the
      initial formation of charge-transfer (CT) complex as an intermediate. The final
      product of the reaction has been isolated and characterized using FTIR, H1 and
      C13 NMR spectroscopy, mass spectrometry, and elemental analysis. The rate of
      formation of product has been measured as a function of time in different
      halocarbon solvents, viz., chloroform, dichloromethane and 1:1 (v/v) mixture of
      two solvents. The pseudo first order and second order rate constants at various
      temperatures for the transformation process were evaluated from the absorbance
      time data. The activation parameters (E(a), DeltaS#, DeltaH#, and DeltaG#) were
      obtained from temperature dependence of rate constants. The influence of
      dielectric constant on the properties of reaction was discussed and the probable
      course of reaction is presented.

PMID- 15863042
TI  - The relevant effect of an intramolecular hydrogen bond on the conformational
      equilibrium of cis-3-methoxycyclohexanol compared to trans-3-methoxycyclohexanol
      and cis-1,3-dimethoxycyclohexane.
AB  - 1H NMR data show that an increase in the concentration of cis-3
      methoxycyclohexanol (cis-3-MCH) shifts the conformational equilibrium from the
      1aa conformer, stabilized by an intramolecular hydrogen bond (IAHB), to the 1ee
      conformer [X(ee) = 44% (at 0.05 molL(-1)) to 59% (at 0.40 molL(-1)), in CCl4],
      which forms intermolecular hydrogen bonds (IEHB), as confirmed by IR data. The
      percentage of 1ee conformer increases with the solvent polarity, from 33%
      (DeltaG(ee-aa) = 1.72 kJmol(-1)) in cyclohexane (C6D12) to 97% (DeltaG(ee-aa) = 
      8.41 kJmol(-1)) in DMSO. For trans-3-methoxycyclohexanol (trans-3-MCH), 1ae and
      1ea conformers are almost equally present in the studied solvents, 1ae increasing
      from 41%, in C6D12 (DeltaG(ae-ea) = 0.84 kJmol(-1)), to 49%, in DMSO (DeltaG(ae
      ea) = 0.13 kJmol(-1)). A value of 18.4 kJmol(-1) for the strength of IAHB in cis
      3-MCH was obtained, from the theoretical data, through the CBS-4M method.

PMID- 15863043
TI  - Vibrational spectra of Na, K, Mn2+, Ni2+ and Zn2+ salts of 1,2,4,5
      benzenetetracarboxylic (pyromellitic) acid--a short hydrogen bond evidence.
AB  - Five salts of 1,2,4,5-benzenetetracarboxylic acid (pyromellitic acid),
      [C6H2(COO)4H4], have been synthesized and investigated by infrared and Raman
      spectroscopy and by single crystal X-ray diffraction methods: sodium salt
      [Na2(H2O)2][C6H2(COO)4H2], potassium salt [K(H2O)3][C6H2(COO)4H3] and transition
      metal salts [M(H2O)6][C6H2(COO)4H2], which M = Mn, Ni and Zn. Crystal structures
      of all five compounds show short intramolecular asymmetric hydrogen bonds (SHB)
      between adjacent carboxyl groups with O...O distance average of 2.40 A. The Raman
      and infrared spectra reported indicate the presence of short hydrogen bonds in
      all salts, in agreement with the X-ray data. The O-H stretching mode [nu(OH)] had
      been observed at about 2500 cm(-1). Deuterated analogues were synthesized and
      their Raman spectra show that nu(OH)/nu(OD) ratio average is about unit. The
      symmetric [nu(sym)(O..H..O)] and asymmetric [nu(asym)(O..H..O)] stretching modes
      have been attributed about 300 and 870 cm(-1), respectively, in all salts, and
      for deuterated analogues, the ratio nu(OH)/nu(OD) to nu(sym)(O..H..O, O..D..O) is
      close to unit like it occurs in nu(OH). The vibrational modes, mainly SHB modes,
      are tentatively assigned by molecular orbital ab initio calculations of
      pyromellitic acid and anions [C6H2(COO)4H3]- and [C6H2(COO)4H2]2-. Geometry
      optimizations showed a good agreement with experimental data. Frequency
      calculation confirms the assignment of specific vibrational modes. Ab initio
      calculations show that nu(C=O) and nu(sym)(COO) are strongly coupled with in
      plane OH bending [delta(OH)]. In Raman spectra of deuterated analogues is
      observed a frequency shift of these bands.

PMID- 15863044
TI  - On the use of wavelet filtering and correlation techniques in atmospheric
      condensed phase spectroscopy.
AB  - The application of wavelet filtering and analysis in spectroscopy is discussed in
      relation to the analysis of complex atmospheric spectra, where contributions from
      condensed phase particles and gas phase molecules are present in the form of
      broad-band features and narrow lines, respectively. The broad-band contribution
      can be extracted as the 'smooth signal' component of the wavelet transform, with
      a large reduction in the size of the corresponding data files. This procedure is
      applied to an investigation of the H2SO4 aerosol content of a series of
      atmospheric spectra measured in the ATMOS missions. The sulfate content of the
      smooth signal is analysed by means of correlation techniques, using a set of
      laboratory reference spectra of varying sulfuric acid concentration and
      temperature. Correlation density maps and correlation curves are used to select
      the most appropriate spectral zones for sulfate analysis and to assess the
      sulfate aerosol content in the atmosphere subsequent to the eruption of the Mount
      Pinatubo volcano.

PMID- 15863045
TI  - Studies on synthesis, infrared and fluorescence spectra of new europium (III) and
      terbium (III) complexes with an beta-diketonate-type ligand.
AB  - A new beta-diketonate-type ligand, N-(2-amino-6-methyl-pyridinyl)ketoacetamide
      (L) and its complexes with europium (III) and terbium (III) were synthesized. The
      complexes were characterized by elemental analysis, infrared spectra and
      conductivity. The europium (III) and terbium (III)-ions were found to coordinate
      to the CO oxygen atoms and pyridine nitrogen atoms. The fluorescence properties
      of these complexes in solid, DMF and CH3OH were studied. The solvent factors
      influencing the fluorescent intensity are discussed.

PMID- 15863046
TI  - Conformational analysis and stereoelectronic effects in trans-1,2
      dihalocyclohexanes: 1H NMR and theoretical investigation.
AB  - The conformational equilibrium of trans-1,2-difluoro- (1), trans-1,2-dichloro-
      (2) and trans-1,2-dibromo-cyclohexane (3) was studied through a combined method
      of NMR, theoretical calculations and solvation theory. The solvent dependence of
      the 3JH1,H2 NMR coupling constants together with theoretical calculations allow
      the direct determination of the conformational equilibria without recourse to
      model compounds. The coupling constants were obtained with the aid of spectrum
      simulation, since these symmetric molecules present complex coupling systems. The
      observed couplings, when analysed by solvation theory and utilising DFT
      geometries (B3LYP/6-311+G**), gave energy values of E(ee) -E(aa) of 0.10, 0.95
      and 1.40 kcalmol(-1) in the vapour phase for 1, 2 and 3, respectively, decreasing
      to -0.63, 0.36 and 0.93 kcalmol(-1) in CCl4 and to -1.91, -0.80 and -0.05
      kcalmol(-1) in DMSO solution. The diaxial preference for all compounds is
      explained by natural bond orbital (NBO) analysis, which shows important
      hyperconjugative effects in this conformation. The "gauche effect" for compounds
      with more electronegative substituents, which are in gauche arrangement in the ee
      conformation, also plays a relevant role in more polar solvents.

PMID- 15863047
TI  - X-ray diffraction, spectroscopic and thermal studies on a potential semiorganic
      NLO material: lithium bis-L-malato borate.
AB  - A semiorganic nonlinear optical material, lithium bis-L-malato borate (LBMB)
      (molecular formula C8H8BLiO10), has been synthesized, and single crystals grown
      from an aqueous solution, by the method of slow evaporation at 30 degrees C.
      Crystals of size up to 7 mm x 3 mm x 2 mm were harvested and characterized by
      powder and single crystal X-ray diffraction and Fourier transform infrared
      techniques to confirm the identity of the compound formed. The TG-DTA results
      establish the good thermal stability of the material. The UV-Vis-NIR spectral
      study reveals that the material has a wide transparency window (230-1500 nm) with
      a lower cutoff at 230 nm. Kurtz powder test with a Nd:YAG laser indicates the
      production of SHG output.

PMID- 15863048
TI  - Study on bromocresol green-cetyltrimethylammonium-deoxyribonucleic acids system
      by resonance light scattering spectrum methods.
AB  - An assay of deoxyribonucleic acids (DNA) determination, with the sensitivity at
      nanogram level, was established in the present study by using a common
      spectrofluorometer to detect the intensity of resonance light scattering (RLS).
      In hexamethylene tetramine (HMTA) buffer (pH 11.00), Bromocresol Green (BCG) and
      deoxyribonucleic acids (DNA) react with cetyltrimethylammonium bromide (CTMAB) to
      form large particles of three-component complex, which results in strong enhanced
      RLS signals characterized by three peaks at 336, 390, and 622 nm and at 336 nm
      that is the strongest of the three enhanced RLS peaks. Mechanistic studies showed
      that the enhanced RLS stems from the aggregation of BCG on DNA through the
      bridged and synergistic effect of CTMAB. Yeast DNA (yDNA), in the range of 0.05
      0.90 ngml(-1), fish sperm DNA (fsDNA) in the range of 0.05-0.80 ngml(-1), and
      calf thymus DNA (ctDNA) in the range of 0.05-0.80 ngml(-1) can be determined if
      2.0 x 10(-6) moll(-1) BCG was employed. The determination limit of yDNA was 12.7
      ngml(-1). Three synthetic samples of yDNA were analyzed with good
      reproducibility.

PMID- 15863049
TI  - Thermodynamic functions of liquid water calculated from the temperature evolution
      of the vibration spectrum contour.
AB  - Configurational contributions of hydrogen bonds to thermodynamic properties of
      water (internal energy, entropy, and heat capacity) are calculated on the basis
      of statistical distributions of frequencies of the OH vibrations of liquid water,
      calculated earlier from the experimental Raman spectra in frameworks of the
      fluctuation theory of hydrogen bonding. Distributions of the energy of hydrogen
      bonds are determined. It is shown by comparison with computer experiments that
      previously established dependence of energy on frequency, E(nu), must be
      considered in this formalism as the effective energy of hydrogen bonding averaged
      over those configurations of hydrogen bridge O-H...O which lead to the given
      frequency nu in the vibrational spectrum. Contribution of van der Waals
      interactions not affecting the frequency shift to heat capacity is evaluated.

PMID- 15863050
TI  - Electronic and infrared spectral and thermal studies on the molecular complex of
      dibenzo-18-crown-6 and iodine.
AB  - The interaction of the crown ether dibenzo-18-crown-6 (DBC) with iodine has been
      studied in CHCl3 at room temperature. The charge-transfer absorptions, far
      infrared and thermal measurements of the formed charge-transfer complex were
      recorded and discussed. The results obtained show the formation of the
      pentaiodide complex with the general formula [(DBC)]+ I5-. The pentaiodide ion,
      I5-, is described as I3-(I2) confirmed by the observation of the characteristic
      absorptions for I3- ion around 365 and 290 nm. In addition, the far infrared
      spectrum of the solid complex shows the three vibrations of I3- unit is at 141,
      113 and 71 cm(-1) assigned to nu(as)(I-I) and nu(s)(I-I) and delta(I3-),
      respectively, while the band related to the vibration of I2 unit is observed at
      180 cm(-1). Vibration analysis of the obtained data shows that the symmetry of I3
      unit could be non-linear with C2v symmetry. The structure of the formed
      pentaiodide complex was further supported by thermal gravimetric analysis
      measurements.

PMID- 15863051
TI  - Vibrational analysis of 1,4-diaminoanthraquinone and 1,5-dichloroanthraquinone. A
      joint FTIR, FT-Raman and scaled quantum mechanical study.
AB  - This work deals with the vibrational spectroscopy of 1,4-diaminoanthraquinone
      (1,4-DAAQ) and 1,5-dichloroanthraquinone (1,5-DCAQ). The mid and far FTIR and FT
      Raman spectra were measured in the condensed state. The fundamental vibrational
      frequencies and intensity of the vibrational bands were evaluated using density
      functional theory (DFT) with the B3LYP functional and 6-31G* basis set. The
      vibrational spectra were interpreted with the aid of normal coordinate analysis
      based on a scaled quantum mechanical force field. The infrared and Raman spectra
      were also predicted from the calculated intensities. Unambiguous vibrational
      assignment of all the fundamentals were made using the potential energy
      distribution (PED).

PMID- 15863052
TI  - FTIR and FT-Raman spectra, vibrational assignments and density functional theory
      calculations of 2,6-dibromo-4-nitroaniline and 2-(methylthio)aniline.
AB  - The FTIR and FT-Raman spectra of 2,6-dibromo-4-nitroaniline (2,6-DB4NA) in solid
      phase and 2-(methylthio)aniline (2-MTA) in liquid phase were measured. The
      geometry and normal vibrations have been obtained from the density functional
      theory (DFT) with the B3LYP method employing the 6-31G* basis set. Scale factors,
      which bring computational frequencies in closer agreement with the experimental
      data, have been calculated for predominant vibrational motions of the normal
      modes. The effects of the amino, bromine, nitro, thio and methyl substituents on
      vibrational frequencies have been investigated. The infrared and Raman spectra
      were also predicted from the calculated intensities. The observed and the
      calculated spectra were found to be in good agreement.

PMID- 15863053
TI  - Environmental effects on the aggregation of some xanthene dyes used in lasers.
AB  - The effect of solvents, halo substituents and surfactants on the aggregation of
      xanthene dyes (fluorescein and eosin Y) has been investigated. It has been found
      that polar protic solvents promote the aggregation of both the dyes while polar
      aprotic solvents hinder the aggregation process. Apolar solvents can disintegrate
      the aggregates previously formed in aqueous medium. The nature of the driving
      forces for aggregation in the two dyes is different. Surfactants bearing charge
      opposite to the dye molecules facilitate aggregation. These observations bear
      direct relevance to the possible use of fluorescein and eosin Y as quantum yield
      standards, photosensitizers, laser dyes and biological labels.

PMID- 15863054
TI  - Evidence of a weak dipole transition moment between the X(1)0g+ and (3)1u(5(3)P1)
      electronic energy states in Cd2.
AB  - Theoretical and experimental evidence of a weak M(z)(R) dipole transition moment
      between the X(1)0g+ ground and (3)1u(5(3)P1) excited states in Cd2 is presented.
      Two independent attempts at recording an excitation spectrum of the (3)1u <--
      X(1)0g+ transition using a laser beam crossed with a supersonic free-jet
      expansion beam are reported. The measurements were performed in a spectral range
      predicted as a result of both ab initio calculations of the electronic energy
      state potentials involved in the transition and a simulation of the excitation
      spectrum. Unfortunately it was impossible to provide unambiguous experimental
      support for the calculated (3)1u-state potential, due to the very poor signal to
      noise ratio. However, the experimental results corroborate the very small values
      of the <(3)1u|M(z)|X(1)0g+> elements obtained in the calculations. This work
      provides as a reliable starting point for further analysis of the (3)1u-state
      characteristics.

PMID- 15863055
TI  - Sensitive determination of nucleic acids using organic nanoparticle fluorescence
      probes.
AB  - This paper describes the preparation of organic nanoparticles by reprecipitation
      method under sonication and vigorous stirring. Transmission electron microscopy
      (TEM) was used to characterize the size and size distribution of the luminescent
      nanoparticles. Their average diameter was about 25 nm with a size variation of +/
      18%. The fluorescence decay lifetime of the nanoparticles also was determined on
      a self-equipped fluorospectrometer with laser light source. The lifetime
      (approximately 0.09 micros) of nanoparticles is about three times long as that of
      the monomer. The nanoparticles were in abundant of hydrophilic groups, which
      increased their miscibility in aqueous solution. These organic nanoparticles have
      high photochemical stability, excellent resistance to chemical degradation and
      photodegradation, and a good fluorescence quantum yield (25%). The fluorescence
      can be efficiently quenched by nucleic acids. Based on the fluorescence quenching
      of nanoparticles, a fluorescence quenching method was developed for determination
      of microamounts of nucleic acids by using the nanoparticles as a new fluorescent
      probe. Under optimal conditions, maximum fluorescence quenching is produced, with
      maximum excitation and emission wavelengths of 345 and 402 nm, respectively.
      Under optimal conditions, the calibration graphs are linear over the range 0.4
      19.0 microgml(-1) for calf thymus DNA (ct-DNA) and 0.3-19.0 microgml(-1) for fish
      sperm DNA (fs-DNA). The corresponding detection limits are 0.25 microgml(-1) for
      ct-DNA and 0.17 microgml(-1) for fs-DNA. The relative standard deviation of six
      replicate measurements is 1.3-2.1%. The method is simple, rapid and sensitive
      with wide linear range. The recovery and relative standard deviation are very
      satisfactory.

PMID- 15863056
TI  - Stereochemistry of new nitrogen containing heterocyclic compound XII. Polymeric
      uranyl complexes of hydrazone compounds.
AB  - Several dioxouranium(VI) heterochelates with tetradentate monobasic hydrazone
      compounds (HL(n)) have been synthesized. The heterochelates of the type
      [(UO2)2(HL(n))(L(n))2(OAc)2(OH2)2]n have been characterized on the basis of
      elemental analyses, IR and electronic spectra, conductance and magnetic
      susceptibility measurements. The complexes are polymeric, non-electrolytes,
      diamagnetic and eight-coordinated. Wilson, G.F. matrix method, Badger's formula,
      Jones and El-Sonbati equations were used to determine the stretching and
      interaction force constants from which the U-O bond distances were calculated.
      The bond distances of these complexes were also investigated.

PMID- 15863057
TI  - Synthesis, properties and thermal studies of oxorhenium(V) complexes with 3
      hydrazino-5,6-diphenyl-1,2,4-triazine, benzimidazolethione and 2
      hydrazinobenzimidazole. Mixed ligand complexes, pyrolytical products and
      biological activity.
AB  - A series of biologically active complexes of oxorhenium(V), were prepared by
      using the organic ligands 3-hydrazino-5,6-diphenyl-1,2,4-triazine (HL1),
      benzimidazolethione (H2L2) and 2-hydrazinobenzimidazole (H2L3). The mixed ligand
      complexes of oxorhenium(V) with the previous ligands and one of the following
      ligands: NH4SCN, 1,10-phenanthroline (1,10-phen), 8-hydroxyquinoline (8-OHquin)
      or glycine (Gly), were isolated. All the binary and mixed ligand complexes have
      monomeric structures and exist in the octahedral configuration. Thermal studies
      on these complexes showed the possibility of structural transformation from
      mononuclear into binuclear ones. The structures of all complexes and the
      corresponding thermal products were elucidated by elemental analyses, IR,
      electronic absorption and 1H NMR spectra, magnetic moments, conductance and TG
      DSC measurements. The antifungal activities of the metal complexes towards
      Alternaria alternata and Aspergilus niger were tested and showed comparable
      behaviour with some well known antibiotics.

PMID- 15863058
TI  - Optical nitrite sensor based on chemical modification of a polymer film.
AB  - A new, low-cost nitrite sensor was developed by immobilizing a direct indicator
      dye in an optical sensing film for food and environmental monitoring. This sensor
      was fabricated by binding gallocyanine to a cellulose acetate film that had
      previously been subjected to an exhaustive base hydrolysis. The membrane has good
      durability (>6 months) and a short response time (<7 s). Nitrite can be
      determined for the range 0.008-1.50 microg/ml with 3delta detection limits of 1
      ng/ml. The method is easy to perform and uses acetylcellulose as a carrier. The
      reagents used for activating the cellulose support are inexpensive, non-toxic and
      widely available.

PMID- 15863059
TI  - Structure and vibrations of AlnNn (n = 3-9) clusters.
AB  - The structure and harmonic vibrations of Al(n)N(n) (n = 3-9) clusters have been
      investigated using the B3LYP (Becke 3-parameter-Lee-Yang-Parr) density functional
      theory. All structures are found to be cumulenic D(nh) rings (equal bonds,
      alternating angles), with one intense out-of-plane mode and three infrared-active
      degenerate modes, of which the highest one is extremely intense and
      asymptotically increases to 1217 cm(-1) for n = 9. Comparisons with C2n clusters
      and B(n)N(n) clusters, the structure and bonding type for the Al(n)N(n) clusters
      are consistent with those of the C2n (n = 3, 5, 7, ...) clusters and the B(n)N(n)
      clusters.

PMID- 15863060
TI  - A study of the anharmonic effects on the vibrational spectra of a realistic
      retinal chromophore model.
AB  - Ab initio and vibrational self-consistent field (VSCF) computations are used to
      investigate the vibrational normal coordinates of the protonated Schiff base
      (PSB) 4-cis-gamma,eta-dimethyl-C9H9 NH2+. The ground and the first excited states
      are investigated. Both harmonic and anharmonic frequencies for the first three
      overtones of the ground and first excited states are reported. Special attention
      is payed to the discussion of the normal coordinates modes that involve the
      central C=C bond which plays a significant role in the isomerization process.

PMID- 15863061
TI  - Steric guided change of electron transfer mechanism in benzene.
AB  - In fluorescence quenching study via electron transfer (ET), the quenching rate
      constant (k(q)) values generally decrease with lowering of quencher
      concentration, since smaller concentration of quencher always leads to a red
      shift in the donor-acceptor (D-A) distance in ET [M. Tachiya, S. Murata, J. Phys.
      Chem. 96 (1992) 8441; S. Murata, M. Tachiya, J. Phys. Chem. 100 (1996) 4064; L.
      Burel, M. Mastafavi, S. Murata, M. Tachiya, J. Phys. Chem. A 103 (1999) 5882].
      However, while doing a comparative study with different carbazole (CZ)
      derivatives-1,4-dicyanobenzene (DCB) systems in benzene (BZ), we observed a
      deviation from that normal behaviour. It was found that for all of them with
      lower quencher (DCB) concentration, k(q) values actually increase instead of the
      expected reduction. Exceptionally, for simple CZ (C12H9N) with decrease in
      concentration of DCB, k(q) values can even reach the order of energy transfer
      (10(11) s(-1)). Interestingly, it is not observed when toluene (TL) or xylene
      (XY) is used as solvent. To explain this unique observation, a sandwich type of
      molecular structure is predicted, where BZ sliding in between CZ and DCB brings
      them closer enough, imparting more through bond character to CZ-DCB interaction
      and hence a higher rate of ET (k(q)) is observed [L. Burel, M. Mastafavi, S.
      Murata, M. Tachiya, J. Phys. Chem. A. 103 (1999) 5882].

PMID- 15863062
TI  - E.S.R., magnetic, electronic and superoxide dismutase studies of imidazolate
      bridged Cu(II)-Cu(II) complexes with ethylenediamine as capping ligand.
AB  - X-band E.S.R., magnetic and electronic spectra of some imidazolate-bridged
      homometallic complexes [(en)2Cu-R-Im-Cu(en)2](ClO4)3 where en, ethylenediamine; R
      ImH, R = H imidazole (ImH); if R = CH3, 2-methylimidazole (M-ImH) and if R =
      C2H5, 2-ethylimidazole (E-ImH), and mononuclear complexes [(en)Cu-dien](ClO4)2
      and [(en)Cu-PMDT](ClO4)2 where dien, diethylenetriamine; PMDT,
      pentamethyldiethylenetriamine have been described. Superoxide dismutase (SOD)
      activity has also been measured and compared with earlier reported complexes. In
      frozen solution at 77 K, the spectra show axial symmetry with a d(x2-y2) ground
      state. Difference in lambda(max) between mononuclear and binuclear complexes was
      found to be approximately 65-75 nm. Magnetic susceptibility and E.S.R. spectral
      measurements for all these binuclear complexes revealed that the copper(II) ions
      are involved in antiferromagnetic exchange interactions propagated by the
      imidazolate bridge.

PMID- 15863063
TI  - On interpretation of a missing spectral band; IR spectra of acidic salts of
      benzohydroxamic acid.
AB  - Using solid benzohydroxamic acid (BHA) as a model compound for its salts, a broad
      absorption at 2730 cm(-1) was generally agreed to represent the nu(OH) band of
      the OH... ON bonds. The absence of nu(OH) band in the IR region 3600-1700 cm(-1)
      was taken to indicate the absence of OH groups in the solid salts. The same
      argument and conclusion was erroneously accepted for lithium (LiBHA) and
      potassium (KBHA) salts of BHA which are not "normal" but acid salts and do
      contain OH groups. X-ray diffraction results allow explanation of this
      discrepancy. The lithium and potassium acid salts have much shorter OH... ON
      bridges (O...O distances of 247 and 245 pm, respectively) than the model compound
      (258 pm). Accordingly, the nu(OH...O) bands in the acidic salts are shifted into
      the crowded 1600-700 cm(-1) interval. Obviously, interpretation of a missing
      spectral band in terms of molecular structure can be misleading when the models
      do not include all possible structural variations.

PMID- 15863064
TI  - Gyromagnetic factor of Cr4+ ions in forsterite.
AB  - The average value of g factor (i.e., g ) of Cr4+ ions in forsterite (Mg2SiO4) is
      calculated with the cubic symmetry approximation from the complete high-order
      perturbation formula of g factor for 3d2 ion in cubic tetrahedral cluster. In the
      formula, the contribution to g factor from the charge-transfer mechanism (which
      is neglected in the crystal-field theory) is considered in addition to that from
      the widely used crystal-field mechanism. From the calculations, the reasonable
      observed value of g is suggested (note: the experimental values of g by various
      authors are scattered) and the important contribution of charge-transfer
      mechanism to g factor can be found.

PMID- 15863065
TI  - Ab initio studies on vibrational spectra of Ni(II), Pd(II), and Pt(II) complexes
      of M'X4(2-) and M'OS3(2-) (M' = Mo, W; X = O, S).
AB  - The vibrational spectra of MM'2X8(2-) and trans-MM'2S6O2(2-) (M = Ni(II), Pd(II),
      Pt(II); M' = Mo, W; X = O, S) are calculated using ab initio method at
      RHF/LanL2DZ level. The calculated vibrational frequencies of MM'2S8(2-) and trans
      MM'2O2S6(2-) are evaluated via comparison with experimental data. The results
      obtained by this method have the deviation <5% for M'S and MS stretching
      vibrational frequencies, however, relatively higher deviation is obtained for M'O
      stretching vibrational frequencies. Some vibrational frequencies of these
      complexes that have not been experimentally reported are also predicted and some
      of the experimental values are assigned.

PMID- 15863066
TI  - The relationship between chemical structure and antimicrobial activity of
      selected nicotinates, p-iodobenzoates, picolinates and isonicotinates.
AB  - Alkaline metal, calcium and magnesium p-iodobenzoates and alkaline metal
      nicotinates, as well as sodium and potassium picolinic and isonicotinates were
      investigated by means of their antimicrobial and chemical properties. The quality
      estimation of the influence of metal cation coordinated to the carboxylic anion
      of the series of studied compounds on their antimicrobial activity as well as on
      the vibrational structure of whole complex in water solution was done. The
      changes in antimicrobial properties and in charge distribution of the complex
      along the position of nitrogen atom in the aromatic ring in sodium and potassium
      complexes were investigated. The analysis of influence of iodine substituent in
      para position on the change of electronic charge distribution of carboxylate
      anion and aromatic ring was done. The relationship between electronic properties
      estimated by vibrational spectroscopy and antimicrobial activity of studied
      complexes was investigated.

PMID- 15863067
TI  - Near-infrared spectroscopy to uranyl arsenates of the autunite and metaautunite
      group.
AB  - A suite of uranyl arsenates have been analysed by near-infrared spectroscopy
      (NIR). The NIR spectra of zeunerite and metazeunerite in the first HOH
      fundamental overtone are different and the spectra of uranyl arsenates of
      different origins in the 6000-7500 cm(-1) region are different. NIR spectroscopy
      provides a method of determination of the hydration of uranyl arsenates and has
      implications for the structure of water in the interlayer. Such a conclusion is
      also supported by the water OH stretching region where considerable differences
      are observed. NIR is an excellent technique for the study of the autunite
      minerals and may be used to distinguish between different autunite phases such as
      the partially dehydrated autunites for example zeunerite and metazeunerite.

PMID- 15863068
TI  - Spectroscopic, redox and magnetic properties of a tetraiminediphenolate iron(II)
      macrocyclic complex: a model compound for iron proteins.
AB  - The title complex [Fe(II)(tidf-H2)(H2O)2](ClO4)2*H(2)O (tidf-H2 =
      tetraiminediphenolate ligand) has been prepared from a transmetallation reaction
      between [Mg2(tidf)](NO3)2*4H2O and an iron(II) salt in methanolic solutions under
      inert atmosphere conditions. It was characterized by analytical, magnetic and
      spectroscopic methods (Mossbauer, FTIR, UV-vis), by cyclic voltammetry as well as
      spectroelectrochemistry.

PMID- 15863069
TI  - Optical poling effect and optical absorption of cyan, ethylcarboxyl and tert
      buthyl derivatives of 1H-pyrazolo[3,4-b]quinoline: experiment and quantum
      chemical simulations.
AB  - We present here results of experimental studies and quantum-chemical simulations
      of optical absorption and optical poling effects performed on a new synthesized
      cyan, ethylcarboxyl and tert-buthyl derivatives of 1H-pyrazolo[3,4-b]quinoline
      incorporated into polymer matrix or dissolved in organic solutions. The
      efficiency of second-order optical susceptibility d vs photoinduced power density
      I(p) clearly saturates to certain magnitude d(eff) at sufficient power densities
      (I(p) > or = 1.3 GW cm(-2)). Comparing experimental data and results of
      semiempirical quantum-chemical simulations one can conclude that there exists
      generally a good correlation between the magnitude of saturated susceptibilities
      d(eff) and macroscopic hyperpolarizabilities for all compounds except the
      chromophore 1,3-dimethyl-6-cyano-[PQ] only. The discrepancy for this compound may
      reflect a specific contribution of surrounding polymer matrix. According to the
      quantum chemical analysis the methyl-containing cyan and ethylocarcoxyl
      derivatives reveal four/five strong absorption bands in the spectral range 200
      500 nm. A substitution of the methyl groups by the phenyl group causes the
      substantial changes of the absorption spectra mainly in the spectral range 240
      370 nm. Measured and calculated absorption spectra manifest rather good agreement
      mainly in the part regarding the spectral positions of the first oscillator
      (absorption threshold). The quantum-chemical PM3 method shows the best agreement
      with experiment. At the same time a considerable broadening almost of all
      absorption bands appears as a characteristic feature of all measured spectra. The
      discrepancies between the calculated and the measured spectra are attributed to
      electron-vibronic coupling as well as to a specific rotational dynamics of phenyl
      rings.

PMID- 15863070
TI  - Investigation of thermal stability and spectroscopic properties in Er3+/Yb3+
      codoped TeO2-Li2O-B2O3-GeO2 glasses.
AB  - The new Er3+/Yb3+ co-doped 70TeO2-5Li2O-(25-x)B2O3-xGeO2 (x = 0, 5, 10, 15 fand
      20 mol.%) glasses were prepared. The thermal stability, absorption spectra,
      emission spectra and lifetime of the 4I(13/2) level of Er3+ ions were measured
      and studied. The FT-IR spectra were carried out in order to investigate the
      structure of local arrangements in glasses. It is found that the thermal
      stability, absorption cross-section of Yb3+, emission intensity and lifetime of
      the 4I(13/2) level of Er3+ increase with increasing GeO2 content in the glass
      composition, while the fluorescence width at half maximum (FWHM) at 1.5 um of
      Er3+ is about 70 nm. The obtained data suggest that this system glass can be used
      as a candidate host material for potential broadband optical amplifiers.

PMID- 15863071
TI  - Inclusion complexes of a bichromophoric diester containing anthracene and
      naphthalene groups with alpha- and beta-cyclodextrins: thermodynamics and
      molecular mechanics.
AB  - Fluorescence and molecular mechanics have been used to study the inclusion
      complexes of the (9-anthryl)-COO-(CH2)2-OOC-(2-naphthyl) bichromophoric compound
      with alpha- and beta-cyclodextrins. Emission spectra upon excitation of the
      naphthalene group denote the presence of non-radiative energy transfer from
      naphthalene to anthracene, which is influenced by the type of CD. Naphthalene
      emission also shows two peaks whose ratio of intensities R is sensitive to the
      medium polarity. The stoichiometry, the formation constants and the changes of
      enthalpy and entropy upon inclusion of complexes formed were obtained from the
      change of R with CD concentration and temperature. Both complexes, in agreement
      with Job's plots, show 1:1 stoichiometry. Quenching, fluorescence depolarization
      and the analysis of R when all the guests are complexed permit us to explain the
      possible location of CDs in the complexes formed. Molecular mechanics
      calculations were also employed to study the formation of 1:1 complexes with both
      alpha- and betaCDs. The study was mainly performed in the presence of water as a
      solvent. Results seem to explain the stoichiometries and geometry for both
      complexes.

PMID- 15863072
TI  - The use of IR, magnetism, reflectance, and mass spectra together with thermal
      analyses in structure investigation of codeine phosphate complexes of d-block
      elements.
AB  - Codeine is an analgesic with uses similar to morphines, but it is of much less
      effect, i.e., it had a mild sedative effect; codeine is usually used as the
      phosphate form (Cod.P) and is often administrated by mouth with aspirin of
      paracetamol. Due to its serious use, if it is in large dose, attention is paid in
      this research to the synthesis and stereochemistry of new iron, cobalt, nickel,
      copper, and zinc complexes of this drug in both solution and the solid states.
      The spectra of these complexes in solution and the study of their stoichiometry
      refer to the formation of 1:1 ratio of metal (M) to ligand (L). The
      steriochemical structures of the solid complexes were studied on the basis of
      their analytical, spectroscopic, magnetic, and thermal data. Infrared spectra
      proved the presence of MO bonds. Magnetic susceptibility and solid reflectance
      spectral measurements were used to infer the structures. The prepared complexes
      were found to have the general formulae [ML(OH)(x)(H2O)(y)](H2O)(z)H3PO4, M:
      Co(II), Ni(II), and Cu(II), x = 1, y = 0, z = 0; M: Fe(II), x = 1, y = 2, z = 1;
      Fe(III), x = 2, y = 1, z = 0; Co(III), x = 0, y = 2, z = 1; Zn(II), x = 1, y = 0,
      z = 3; and L: (Cod.P) of the general formula C18H24NO7P (anhydrate). Octahedral,
      tetrahedral, and square planer structures were proposed for these complexes
      depending upon the magnetic and reflectance data and were confirmed by detailed
      mass and thermal analyses comparative studies.

PMID- 15863073
TI  - Separation and identification of multicomponent mixture by thin-layer
      chromatography coupled with Fourier transform-infrared microscopy.
AB  - A fast and convenient method based on coupled thin-layer chromatography (TLC)
      with Fourier transform infrared (FTIR) microscopy has been established for
      separation and identification of multicomponent mixtures. In this study, the
      method was developed and consummated with more perfect TLC spots transferral
      process and consistent FTIR testing conditions. A newly developed technique,
      solid-phase extract (SPE) was introduced for sample pre-treatment instead of
      using traditional column chromatography. It is a new field for SPE that has
      already been widely applied in many other fields. It not only overcomes the
      backwards (low separation efficiency, time consuming and solvent consumption) of
      column chromatography but also makes it much easier to choose an optimum TLC
      sheet and to set suitable TLC loading. With all the above-mentioned modifications
      and supplements, the analytical method of coupled TLC with FTIR microscopy for
      separation and identification of multicomponent mixtures becomes more convenient
      and more efficient. In addition, a very complex sample (a die-cast release agent)
      was used as an example to demonstrate the technique.

PMID- 15863074
TI  - The synthesis and characterisation of Sn(IV) complexes of 2,6-pyridine
      dicarboxylate--the molecular structure of divinyltin(IV) derivative.
AB  - A series of organotin(IV) derivatives were obtained employing 2,6
      pyridinedicarboxylate as ligand: [{SnBu3(OOC)2C5H3N}n] (1), [SnBuCl(OOC)2C5H3N]
      (2) and [Sn(CHCH2)2(OOC)2C5H3N] (3). They were fully characterised by
      multinuclear NMR [1H, 13C{1H}, and 119Sn{1H}], IR spectroscopies and elemental
      analysis. In addition suitable crystals of (3) have shown a dimmeric arrangement
      by X-ray crystallographic studies, held together by Sn-O intermolecular
      interactions which persists in solution. The crystal packing shows hydrogen bonds
      joining the dimmers, forming two infinite one-dimensional chain. Each monomer
      comprises a Sn(IV) centre bonded to a pyridinecarboxylate-containing ring,
      through both nitrogen and oxygen donor atoms. It is also co-ordinated by a water
      molecule and two vinyl groups.

PMID- 15863075
TI  - Role of the anion in the alkali halides interaction with D-ribose: a 1H and 13C
      NMR spectroscopy study.
AB  - The alkali halides interaction with d-ribose in D2O solutions was studied by 1H
      and 13C NMR spectroscopy. The observed changes in the NMR spectra are interpreted
      according to a model in which the hydroxyls rich region, from C1 to C4, interacts
      with the cation while the CH2 group at C5 on the opposite side of the sugar
      interacts with the anion. It seems, during the salt-sugar interaction, cation and
      anion preserve, at least partially, their ion-pair character. The cooperative
      interaction of the sugar hydroxyl groups with the cation leads to a polarization
      within the sugar molecule, which favors the anion interaction with its most
      positive region. A correlation between the chemical shift of C5 atom and the
      atomic number of the anion was observed, which is discussed as a neighboring
      paramagnetic effect; as higher is the halogen atom more pronounced is the
      resulting shift of the C5 signal. The anion effect is weak but also observed in
      the 13C signals of those carbon atoms bound to hydroxyl groups where the
      interaction is predominant with the cation. The 1H signal of the anomeric protons
      and the relative population of isomers in the alkali halide solution also show an
      anion dependence.

PMID- 15863076
TI  - Osteogenic protein-1 is most effective in stimulating nucleus pulposus and
      annulus fibrosus cells to repair their matrix after chondroitinase ABC-induced in
      vitro chemonucleolysis.
AB  - BACKGROUND CONTEXT: Chondroitinase ABC (C-ABC) is used in chemonucleolysis to
      degrade, with great specificity, the chondroitin sulfate and dermatan sulfate
      chains of proteoglycans (PGs). A recent study showed that osteogenic protein-1
      (OP-1) is very effective in stimulating the production and formation of the
      extracellular matrix by rabbit intervertebral disc cells. PURPOSE: To test the
      hypothesis that the repair of the extracellular matrix of the intervertebral disc
      after chemonucleolysis by C-ABC can be stimulated by exposure to a low dose of a
      growth factor, OP-1. STUDY DESIGN: An alginate bead cell culture system was used
      to monitor the effects of OP-1 on the repair of damaged matrices after in vitro
      chemonucleolysis with C-ABC. METHODS: Rabbit nucleus pulposus (NP) or annulus
      fibrosus (AF) cells cultured for 2 weeks in alginate gel were briefly exposed to
      low concentrations of C-ABC and then cultured in the presence or absence of OP-1.
      The control group was cultured without enzyme treatment for the same period in
      the absence of OP-1. At each time point, the contents of DNA and proteoglycan
      accumulation and proteoglycan synthesis were measured. RESULTS: NP or AF cells
      cultured in alginate beads, which were digested with C-ABC and then treated with
      OP-1, recover PG content more rapidly than those cultured in the absence of OP-1.
      The major contributor to the superior matrix repair in the cells treated with OP
      1 was an up-regulation of proteoglycan synthesis. CONCLUSIONS: OP-1 was effective
      in stimulating matrix repair by NP and AF cells after their matrices were nearly
      totally depleted of sulfated glycosaminoglycans. The use of OP-1 after
      chemonucleolysis might help the disc to regain biomechanical strength, weakened
      by enzyme digestion, by stimulating matrix metabolism.

PMID- 15863077
TI  - Hydroxyapatite-coating of pedicle screws improves resistance against pull-out
      force in the osteoporotic canine lumbar spine model: a pilot study.
AB  - BACKGROUND CONTEXT: In patients with spinal osteoporosis, the early achievement
      and maintenance of a biological bond between the pedicle screw and bone is
      important to avoid screw loosening complications. There are few reports of in
      vivo investigations involving biomechanical and histological evaluations in the
      osteoporotic spine. PURPOSE: To evaluate the effect of hydroxyapatite (HA)
      coating on the pedicle screw in the osteoporotic lumbar spine and to investigate
      the relationship between resistance against the screw pull-out force and bone
      mineral density (BMD) of the vertebral body. STUDY DESIGN/SETTING: Mechanical and
      pathological investigations in the lumbar spine. METHODS: Two 24-month-old female
      beagle dogs were fed a calcium-free dog chow for 6 months after ovariectomy
      (OVX). BMD (in g/cm2) was measured by dual energy X-ray absorptiometry at pre-OVX
      and 6 months after OVX. Pedicle screws were placed from L1 to L6 at 6 months
      after OVX. Twenty-four pure titanium cortical screws (Synthes, #401-114) were
      used as pedicle screws (Ti-PS). Of these, 12 screws had HA-coating (HA-PS). The
      HA-PS screws were inserted into the right pedicles and the Ti-PS were inserted
      into the left pedicles. Ten days after this procedure, the lumbar spines were
      removed en bloc for screw pull-out testing and histological evaluation. RESULTS:
      The mean BMD value of the lumbar vertebrae 6 months after the OVX was 0.549+/
      0.087 g/cm2, which was significantly less than the pre-OVX mean BMD of 0.603+/
      0.092 g/cm2 (p < 0.001). The mean resistance against the pull-out force for the
      HA-PS was significantly greater at 165.6+/-26.5N than in the Ti-PS (103.1+/
      30.2N, p < .001). The histological sections in the HA-PS clearly revealed new
      bone bonding with the apatite coating but only fibrous tissue bonding in the Ti
      PS. CONCLUSIONS: The results of this study showed that the resistance to the pull
      out force of HA-PS is 1.6 times that of Ti-PS. Furthermore, HA-PS has superior
      biological bonding to the surrounding bone, as early as 10 days after surgery in
      this osteoporotic spine model. Thus, in patients with osteoporosis, coating of
      the pedicle screw with HA may provide better stability and bonding between the
      pedicle screw and bone in the early postoperative period.

PMID- 15863078
TI  - Preliminary outcomes and efficacy of the first 360 consecutive kyphoplasties for
      the treatment of painful osteoporotic vertebral compression fractures.
AB  - BACKGROUND CONTEXT: Osteoporosis is a major cause of morbidity in worldwide
      elderly populations. Patients may become susceptible to vertebral compression
      fractures (VCFs) from low-impact situations. For patients who have failed
      conventional, palliative medical therapy, kyphoplasty not only reduces pain
      associated with vertebral fractures, but also offers a minimally invasive
      procedure with the potential to address fracture reduction and spinal sagittal
      alignment. Kyphoplasty involves expanding an inflatable balloon tamp to create a
      cavity within a vertebral body before cement deposition. PURPOSE: To evaluate the
      safety and efficacy of kyphoplasty to reduce and fix painful osteoporotic VCFs.
      STUDY DESIGN/SETTING: A retrospective, single-arm cohort study of consecutive
      kyphoplasty patients treated at a single center. PATIENT SAMPLE: Three hundred
      sixty VCFs were treated during 254 kyphoplasty procedures on 222 osteoporotic
      patients (mean age, 76 years [range, 28-98]; 28% male and 72% female). OUTCOME
      MEASURES: Patient-reported pain ratings were examined. Cement extravasation was
      monitored by intraoperative fluoroscopy and on postoperative radiographs.
      Anterior and midline vertebral height were assessed from standing, lateral
      radiographs obtained preoperatively and postoperatively. The number of patients
      who returned with symptomatic, new fractures was monitored. Perioperative
      complications were recorded. Mean follow-up occurred 21 months after kyphoplasty
      (range, 6 months through 36 months). RESULTS: Immediate pain relief was reported
      by 89% of patients by the first follow-up visit. One patient experienced
      postoperative pain as a result of radiculopathy related to bone filler leakage
      into the foramen. The remaining patients had persistent pain and were diagnosed
      with either a new fracture or underlying degenerative disc disease. Greater than
      or equal to 20% restoration of lost vertebral height (anterior) was observed in
      63% of fractures with an overall mean restoration of 30%, and > or = 20%
      restoration of lost vertebral height (midline) was detected in 69% of fractures
      with an overall mean restoration of 50%. In this cohort, 12% (30/254) of the
      patients required additional kyphoplasty procedures to treat 36 symptomatic, new
      adjacent and remote fractures. No device-related complications occurred.
      CONCLUSIONS: Kyphoplasty is a safe and effective, minimally invasive procedure
      for relief of pain associated with VCF. In our series we also demonstrated some
      restoration of vertebral height and partial correction of sagittal alignment.

PMID- 15863079
TI  - A factor analysis of lumbar intradiscal electrothermal annuloplasty outcomes.
AB  - BACKGROUND CONTEXT: Intradiscal electrothermal annuloplasty (IDET) is a minimally
      invasive procedure for managing chronic discogenic low back pain (LBP). Although
      there have been numerous reports of IDET outcome rates, few have dissected the
      detailed factors affecting those outcomes. PURPOSE: To evaluate how heating
      variables and the number of catheters used affect the outcomes and pain flare-up
      in LBP patients treated with IDET. STUDY DESIGN/SETTING: Retrospective analysis.
      PATIENT SAMPLE: Data were gathered on the basis of chart records from January 6,
      1999 to January 6, 2000. Twenty-five cases treated at a single level with disc
      protrusion < or = 2 mm, nonfocal neurological abnormalities, and positive
      discogram with annular tear were studied. Six patients were unavailable for
      follow-up at 16 months. OUTCOME MEASURES: All assessments were incorporated into
      our own evaluation sheet, completed before the procedure and at follow-up.
      Assessments included the following: 1) Visual Analog Scale (VAS) and 2) Back Pain
      Improvement Scales (BPI) preoperatively and at 8 and 16 months post-procedure.
      Post-procedure flare-up of the pain was defined as the pain aggravation after the
      IDET procedure from the pre-procedure baseline pain. It was evaluated by a 10
      point numeric rating scale, ranging from no aggravated pain "0" to the worst
      aggravated pain "10". METHODS: Patients were partitioned into a single-catheter
      group and a double-catheter group. In these two groups, statistical analyses were
      done to compare the outcomes and flare-up duration and intensity. In each
      catheter group, the correlation coefficients were analyzed between heating
      variables such as heating duration/temperature and two outcome scales. Then, two
      outcome scales relative to intensity and duration of post-IDET flare-up were
      analyzed with Pearson's correlation. Also the combined effect of the heating
      duration and temperature was evaluated as a thermal dosage, which is the total
      amount of heat developed during the procedure. It was calculated by multiplying
      the temperature and its heating duration above a starting temperature of 65
      degrees C. RESULTS: Comparing the single- and double-catheter groups, patients
      placed in the single-catheter group showed significantly shorter flare-up
      duration (11.00+/-19.17 vs. 24.89+/-20.84 days, p < .05). In the single-catheter
      group, the flare-up duration manifested moderate linear correlation with heating
      variables (0.580 with temperature, 0.519 with thermal dosage, p < .05). Also, the
      improvements of pain with VAS displayed moderate reverse correlation with heating
      variables at 8 months (-.436 with temperature, -0.439 with thermal dosage, p <
      .1). In the double-catheter group, the Back Pain Improvement% had strong reverse
      correlations with temperature and thermal dosage at 8 months (-.735 and -.729, p
      < .05). The correlation between the improvement of VAS and temperature yielded a
      moderate reverse relationship (-.619, p < 0.1). These correlations were not,
      however, observed at 16 months in either the single- or double-catheter groups.
      CONCLUSIONS: Higher temperatures and larger total heating doses during IDET
      procedures with catheters placed in the outer annulus may increase the duration
      of post-procedure pain flare-ups and lead to less favorable outcomes at 8 months
      follow-up. The long-term outcomes at 16 months may, however, not be affected by
      these heating variables.

PMID- 15863081
TI  - Accuracy of single-time, multilevel registration in image-guided spinal surgery.
AB  - BACKGROUND CONTEXT: Computerized frameless stereotactic image-guidance has been
      used in recent years to improve the accuracy and safety of pedicle screw
      placement during spine surgery. Because the possibility of intervertebral motion
      exists, and because the patient is usually in a different position when
      preoperative imaging is performed compared with the operative position, it has
      been suggested that the imaging model of the complete lumbar spine and the
      surgically exposed lumbar spine may be significantly discordant. Consequently,
      current protocols suggest registering each spinal level (single-level
      registration) separately before pedicle screw placement at that level, a time
      consuming process. PURPOSE: To assess the accuracy of single-time multilevel
      registration for multilevel pedicle screw placement during image-guided, computer
      assisted spine surgery, in the setting of degenerative disorders of the lumbar
      spine. STUDY DESIGN/SETTING: This is a prospective clinical and radiological
      study of 45 patients with degenerative disorders of the lumbar spine who
      underwent instrumented fusion with the use of single-time multilevel registration
      computer-assisted, image-guided tomography. The accuracy of the pedicle screws
      placement was confirmed on the basis of a protocol that included intraoperative
      spontaneous electromyographic (EMG) recordings, direct pedicle visualization, and
      computer tomography (CT) scans when clinically indicated during the follow-up
      period. PATIENT SAMPLE: Forty-five consecutive patients who fulfilled the
      criteria of computer-assisted, image-guided tomography pedicle screw placement
      for degenerative lumbar spine disease without overt instability. OUTCOME
      MEASURES: The principal outcome measure was the accuracy of pedicle screw
      placement with single-time multilevel registration for multilevel pedicle screw
      placement during image-guided, computer-assisted spine surgery; postoperative CT
      performed for clinical indications during the follow-up course was used for the
      assessment of pedicle screw placement. METHODS: Patients were assessed clinically
      before and after the operation. Data from 45 consecutive cases of image-guided,
      computer-assisted lumbar spinal fusion were statistically analyzed to determine
      the relationship between the number of levels registered during single-time
      registry and the mean registration error (MRE). Intraoperative spontaneous EMG,
      direct visualization, and postoperative CT scans were used to assess the accuracy
      of pedicle screw insertion. RESULTS: None of the patients involved in this study
      experienced clinical sequelae of improper pedicle screw placement. MREs after
      surface mapping and after point merge were small (less than 1.00 mm and less than
      3.00 mm, respectively). During the intraoperative assessment of the pedicle
      screws placement, no significant spontaneous EMG activity was recorded and the
      pedicular walls were found intact in direct visualization. The postoperative CT
      scans showed in 10 patients accurate placement in 55 of the 57 pedicle screws
      with expansion of the medial wall in two screws. CONCLUSIONS: Single-time,
      multilevel registration may decrease operative time relative to repeated, single
      level registrations, without compromising the increased accuracy of pedicle screw
      placement afforded by this technique in the setting of degenerative disorders of
      the lumbar spine. Despite the advantages in computer-guided image surgery,
      cautious application in the individual patient is recommended until more
      comprehensive data can be gathered in specific degenerative pathology with overt
      instability; thus the knowledge of the anatomy remains crucial.

PMID- 15863083
TI  - Pulmonary injury in patients undergoing complex spine surgery.
AB  - BACKGROUND CONTEXT: Previous reports have shown that 15% of patients who undergo
      sequential anterior, then posterior, surgical corrections for spinal deformities
      demonstrate evidence of acute lung injury. By analyzing the bronchoalveolar
      lavage (BAL) fluid from these patients for evidence of acute inflammation, we
      might gain some insight into the etiology of this acute lung injury. PURPOSE: To
      elucidate the etiology of acute lung injury after corrective surgery for adult
      spinal deformities. STUDY DESIGN/SETTING: Fifteen adult patients with scoliosis
      scheduled for elective sequential anterior then posterior corrective (A/P) spinal
      deformity surgery. PATIENT SAMPLE: Consecutive adult patients with scoliosis
      scheduled for elective corrective surgery with the author (OBA). OUTCOME
      MEASURES: Patients were assessed for postoperative respiratory complications by
      oxygen requirements, continued mechanical ventilation, and radiological evidence
      of diffuse bilateral interstitial or alveolar infiltrates. An acute pulmonary
      inflammatory response included the presence of inflammatory cells and elevated
      cytokines in BAL fluid. METHODS: BAL were performed after induction of anesthesia
      but before surgery, at the completion of surgery, and on the morning after
      surgery with the patient still intubated. BAL fluid was analyzed for inflammatory
      cells and cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF
      alpha) levels. Patients were assessed postoperatively for increased pulmonary
      vascular resistance, radiological evidence of diffuse bilateral alveolar
      infiltrates, and the requirement for ventilatory support beyond the first
      postoperative day (POD1). RESULTS: The cell counts of BAL fluid demonstrated
      significant increases in neutrophils, lymphocytes, and lipid laden macrophages
      (LLMAC) with surgery. The concentration of the cytokines IL-6 and TNF-alpha also
      increased with surgery. The elevations in BAL inflammatory cells and cytokine
      levels correlated positively with increased pulmonary vascular resistance and the
      requirement for mechanical ventilation. CONCLUSIONS: After A/P spine fusions,
      patients have evidence of an acute inflammatory pulmonary injury. Several
      etiologies exist for this finding, including blood and fluid infusions, direct
      trauma to the lung, a systemic inflammatory response, and the embolization of fat
      and bone-marrow debris. The presence of LLMAC in the lungs of these patients and
      the finding that the patient with the requirement for the longest ventilatory
      support also had the highest BAL LLMAC count, suggest that the embolization of
      fat and bone debris released from the spine during surgery may be at least
      partially responsible for the lung injury. Further studies on the mechanism of
      lung injury during this procedure are warranted.

PMID- 15863084
TI  - Comparison of human lumbar facet joint capsule strains during simulated high
      velocity, low-amplitude spinal manipulation versus physiological motions.
AB  - BACKGROUND CONTEXT: Spinal manipulation (SM) is an effective treatment for low
      back pain (LBP), and it has been theorized that SM induces a beneficial
      neurophysiological effect by stimulating mechanically sensitive neurons in the
      lumbar facet joint capsule (FJC). PURPOSE: The purpose of this study was to
      determine whether human lumbar FJC strains during simulated SM were different
      from those that occur during physiological motions. STUDY DESIGN/SETTING: Lumbar
      FJC strains were measured in human cadaveric spine specimens during physiological
      motions and simulated SM in a laboratory setting. METHODS: Specimens were tested
      during displacement-controlled physiological motions of flexion, extension,
      lateral bending, and axial rotations. SM was simulated using combinations of
      manipulation site (L3, L4, and L5), impulse speed (5, 20, and 50 mm/s), and pre
      torque magnitude (applied at T12 to simulate patient position; 0, 5, 10 Nm). FJC
      strains and vertebral motions (using six degrees of freedom) were measured during
      both loading protocols. RESULTS: During SM, the applied loads were within the
      range measured during SM in vivo. Vertebral translations occurred primarily in
      the direction of the applied load, and were similar in magnitude regardless of
      manipulation site. Vertebral rotations and FJC strain magnitudes during SM were
      within the range that occurred during physiological motions. At a given FJC,
      manipulations delivered distally induced capsule strains similar in magnitude to
      those that occurred when the manipulation was applied proximally. CONCLUSIONS:
      FJC strain magnitudes during SM were within the physiological range, suggesting
      that SM is biomechanically safe. Successful treatment of patients with LBP using
      SM may not require precise segmental specificity, because the strain magnitudes
      at a given FJC during SM do not depend upon manipulation site.

PMID- 15863085
TI  - Influence of the type of load on the cervical spine: a study on Congolese
      bearers.
AB  - BACKGROUND CONTEXT: Cervical spine suffers degenerative changes with age and
      activity. PURPOSE: The aim is to study the cervical spine of African head bearers
      by analyzing clinical changes and radiographic degenerative signs in comparison
      with a control group. STUDY DESIGN: Two groups of bearers, 28 bearers of heavy
      loads (50 to 60 kg) over short stretches and 33 bearers who carried bundles or
      lighter loads (30 to 35 kg) over long distances were clinically and
      radiographically examined and compared with a control group of 36 building
      industry workers who did not bear weights on their heads. METHODS: We noted the
      age, height, weight, body mass index (BMI), weight of load, years they had been
      working, width and length of the neck and any painful symptoms. We carried out a
      functional exploration of the cervical spine and a lateral radiograph of the
      cervical spine to assess degenerative changes and quantified the degenerative
      changes in the vertebral bodies and the discs. The angle of lordosis was
      measured. RESULTS: We found more prolapsed discs (p < .01) in the heavy-load
      bearing group than in the control group. The heavy-load bearers had larger neck
      width (p < .01) and more disc herniations (p < .05) than the bundler bearers. The
      frequency of prolapsed discs was higher at C5-C6 and C6-C7 levels. The listhesis
      was more frequent among bundle bearers than in heavy-load bearers and control
      group. A correlation between the number of disc herniations and age (p < .01) and
      years of work (p < .05) was observed. When all the bearers were compared with the
      control group, the differences found were the number of prolapsed discs,
      stiffness in the neck and reported pain (p < .01). CONCLUSION: Load bearing on
      the head, particularly bearers of heavy loads, produced more radiographic
      degenerative signs, much stiffness in the neck and more reported pain than the
      control group.

PMID- 15863086
TI  - Influence of spine morphology on intervertebral disc loads and stresses in
      asymptomatic adults: implications for the ideal spine.
AB  - BACKGROUND CONTEXT: Sagittal profiles of the spine have been hypothesized to
      influence spinal coupling and loads on spinal tissues. PURPOSE: To assess the
      relationship between thoracolumbar spine sagittal morphology and intervertebral
      disc loads and stresses. STUDY DESIGN: A cross-sectional study evaluating
      sagittal X-ray geometry and postural loading in asymptomatic men and women.
      PATIENT SAMPLE: Sixty-seven young and asymptomatic subjects (chiropractic
      students) formed the study group. OUTCOME MEASURES: Morphological data derived
      from radiographs (anatomic angles and sagittal balance parameters) and
      biomechanical parameters (intervertebral disc loads and stresses) derived from a
      postural loading model. METHODS: An anatomically accurate, sagittal plane,
      upright posture, quadrilateral element model of the anterior spinal column (C2
      S1) was created by digitizing lateral full-spine X-rays of 67 human subjects (51
      males, 16 females). Morphological measurements of sagittal curvature and balance
      were compared with intervertebral disc loads and stresses obtained using a
      quadrilateral element postural loading model. RESULTS: In this young (mean 26.7,
      SD 4.8 years), asymptomatic male and female population, the neutral posture spine
      was characterized by an average thoracic angle (T1-T12) = +43.7 degrees (SD 11.4
      degrees ), lumbar angle (T12-S1) = -63.2 degrees (SD 10.0 degrees ), and pelvic
      angle = +49.4 degrees (SD 9.9 degrees ). Sagittal curvatures exhibited relatively
      broad frequency distributions, with the pelvic angle showing the least variance
      and the thoracic angle showing the greatest variance. Sagittal balance
      parameters, C7-S1 and T1-T12, showed the best average vertical alignment (5.3 mm
      and -0.04 mm, respectively). Anterior and posterior disc postural loads were
      balanced at T8-T9 and showed the greatest difference at L5-S1. Disc compressive
      stresses were greatest in the mid-thoracic region of the spine, whereas shear
      stresses were highest at L5-S1. Significant linear correlations (p < .001) were
      found between a number of biomechanical and morphological parameters. Notably,
      thoracic shear stresses and compressive stresses were correlated to T1-T12 and T4
      hip axis (HA) sagittal balance, respectively, but not to sagittal angles. Lumbar
      shear stresses and body weight (BW) normalized shear loads were correlated with
      T12-S1 balance, lumbar angle, and sacral angle. BW normalized lumbar compressive
      loads were correlated with T12-S1 balance and sacral angle. BW normalized lumbar
      disc shear (compressive) loads increased (decreased) significantly with
      decreasing lumbar lordosis. Cervical compressive stresses and loads were
      correlated with all sagittal balance parameters except S1-HA and T12-S1. A
      neutral spine sagittal model was constructed from the 67 subjects. CONCLUSIONS:
      The analyses suggest that sagittal spine balance and curvature are important
      parameters for postural load balance in healthy male and female subjects.
      Morphological predictors of altered disc load outcomes were sagittal balance
      parameters in the thoracic spine and anatomic angles in the lumbar spine.

PMID- 15863087
TI  - Intraligamentous injection of sclerosing solutions (prolotherapy) for spinal
      pain: a critical review of the literature.
AB  - BACKGROUND CONTEXT: The injection of various solutions aimed at producing a
      sclerosing effect has been used to treat soft tissues injuries (eg, inguinal
      hernia) for more than 100 years. In the 1930s, this treatment approach was
      applied to injured joints in an attempt to stimulate connective tissue repair.
      Although several studies have been published about this method of treatment for
      various orthopedic and spinal indications (termed prolotherapy), its use remains
      controversial. PURPOSE: To conduct a critical review of the literature on
      prolotherapy for spinal pain. STUDY DESIGN/SETTING: Critical review of the
      literature. METHODS: Computerized medical literature databases (Medline, CINAHL,
      Mantis, Cochrane Central Register of Controlled Trials) were searched to uncover
      all published information about the use of sclerosing injections in humans with
      spinal pain disorders. Search results were reviewed for relevance, and
      information was abstracted from full-text articles. RESULTS: Our search uncovered
      almost 200 reference materials in various media related to prolotherapy,
      including 31 clinical studies related to spinal pain. There were 26 observational
      cohorts and 5 randomized clinical trials (RCTs). Indications in these studies
      were low back pain (22), neck pain (3), cervical headaches (3) and dorsal or
      thoracic pain (3). A total of 20 sclerosing solutions were used in these studies;
      the most common was a mixture of dextrose 12.5%, glycerin 12.5%, phenol 1.25% and
      lidocaine 0.25%. Wide variations were found in treatment protocols, such as dose,
      number of treatments and use of adjunct therapies. Most cohort studies were only
      of moderate quality and varied greatly in the substances injected and the use of
      co-interventions. Most clinical studies reported positive results such as
      decreased pain or disability, although differences between treatment and control
      groups did not always reach statistical significance. Commonly reported adverse
      reactions to this treatment include temporary postinjection pain and stiffness. A
      handful of more serious adverse events were reported in the 1950s and 1960s with
      stronger or unknown solutions. CONCLUSION: Prolotherapy describes a variety of
      treatment approaches rather than a specific protocol. Results from clinical
      studies published to date indicate that it may be effective at reducing spinal
      pain. Great variation was found in the injection and treatment protocols used in
      these studies that preclude definite conclusions. Future research should focus on
      those solutions and protocols that are most commonly used in clinical practice
      and have been used in trials reporting effectiveness to help determine which
      patients, if any, are most likely to benefit from this treatment.

PMID- 15863088
TI  - Transient kyphotic deformity of the thoracolumbar junction resulting from a large
      abdominal cyst: a case report.
AB  - BACKGROUND CONTEXT: Pronounced kyphosis of the thoracolumbar junction is a common
      orthopedic problem in adolescents and may require prolonged bracing therapy or
      correction spondylodesis. PURPOSE: To describe a case where a kyphotic deformity
      was related to gynecological instead of spine pathology. STUDY DESIGN: Case
      report. METHODS: A 17-year-old girl presented with a structural hyperkyphosis of
      the thoracolumbar spine and radiographic changes of the involved vertebral end
      plates. RESULTS: The thoracolumbar hyperkyphosis appeared to have evolved from a
      massive intra-abdominal ovarian cyst. Endoscopic paracentesis of the cyst
      resulted in a complete regression of the hyperkyphosis. CONCLUSIONS: A
      hyperkyphosis is not always related to spine pathology, and other potential
      causes must be excluded before bracing therapy is initiated.

PMID- 15863089
TI  - Epidural hematoma after immobilization of a "hangman's" fracture: case report and
      review of the literature.
AB  - BACKGROUND CONTEXT: Neurologic deterioration after immobilization of traumatic
      spondylolisthesis of the axis rarely occurs because of the decompressive nature
      of the injury itself and the large amount of space available for the cord in the
      upper cervical spine. PURPOSE: To document neurologic deterioration after
      reduction (without the use of traction) and halo immobilization of a Type IIA
      traumatic spondylolisthesis of the axis (hangman's fracture) secondary to an
      epidural hematoma. STUDY DESIGN/SETTING: Case report. PATIENT SAMPLE AND OUTCOME
      MEASURES: The patient population consisted of one patient; no outcome measures
      were used. METHODS: The medical record and radiographic studies of a 27-year-old
      patient involved in a motor vehicle crash that resulted in a traumatic
      spondylolisthesis of the axis were retrospectively reviewed, and a review of the
      English literature was performed. RESULTS: Upon evaluation, the patient was found
      to have, in addition to other injuries, a Type IIA hangman's fracture of the C2
      vertebra, which was stabilized in a halo. Shortly thereafter, the patient
      developed a gradual progressive neurologic deficit. Magnetic resonance imaging
      revealed the presence of a large epidural hematoma with cord compression treated
      with posterior laminectomy and transdural decompression of an anterior hematoma.
      Postoperatively, the patient's neurologic examination improved and returned to
      normal within 6 months. CONCLUSION: An epidural hematoma can occur after
      traumatic spondylolisthesis of the axis, but its symptoms may not present until
      after the spondylolisthesis is treated.

PMID- 15863090
TI  - Intracranial hypotension and recurrent pleural effusion after snow-boarding
      injury: a manifestation of cerebrospinal fluid-pleural fistula.
AB  - BACKGROUND DATA: Intracranial hypotension causing postural headaches has been
      described after occult and postsurgical cerebrospinal fluid (CSF) leaks and
      rarely isolated lumbar punctures. The occurrence of a CSF-pleural communication
      is much rarer, and a high level of suspicion aids in prompt recognition. PURPOSE:
      Early detection and anatomic delineation of the site of CSF-pleural fistula
      allows prompt intervention, results in resolution of symptoms and prevents the
      complication of meningitis. STUDY DESIGN: A case of intracranial hypotension with
      postural headaches is described after spinal surgery, with demonstration on
      computed tomography (CT) myelography of a rare CSF-pleural fistula. METHODS: The
      clinical presentation, postoperative intervention and imaging as well as
      laboratory data are presented. RESULTS: Chest X-ray showed recurrent pleural
      effusion after placement of chest tube, and serial head CT studies revealed
      decreasing ventricular size with development of severe headaches. Myelogram and
      CT postmyelogram demonstrate the CSF-pleural communication, allowing appropriate
      surgical repair. CONCLUSION: Severe headaches with a recurrent pleural effusion
      after thoracic spinal surgery may indicate presence of a CSF-pleural fistula, an
      unusual complication of thoracic spinal surgery.

PMID- 15863091
TI  - Use of intraoperative isocentric C-arm 3D fluoroscopy for sextant percutaneous
      pedicle screw placement: case report and review of the literature.
AB  - BACKGROUND CONTEXT: Three-dimensional (3D) fluoroscopy-based image guidance
      system using an isocentric C-arm (Iso-C) fluoroscope was shown to be as effective
      as computed tomography-based systems in guiding the accurate percutaneous
      placement of lumbar pedicle screws in cadavers. To date, however, no description
      is available of the intraoperative use of 3D fluoroscopy to guide lumbar pedicle
      screw placement in an actual spinal fusion procedure. PURPOSE: We report a case
      in which isocentric 3D fluoroscopic images, along with image-guidance software,
      were used to guide the placement of percutaneous pedicle screws for fusion in a
      patient with degenerative spondylolisthesis. STUDY DESIGN/SETTING: Operating room
      of a large academic medical center during the placement of percutaneous pedicle
      screws in a patient with degenerative spondylolisthesis. METHODS: A percutaneous
      dynamic reference array was attached to the L3 spinous process. A satisfactory
      image set was obtained and automatically registered. The L4 and L5 pedicles were
      localized, and pedicle holes were then cannulated, drilled and tapped. A screw
      was then inserted using the Sextant system for percutaneous pedicle screws. In
      this manner, bilateral pedicle screws were inserted into the L4-L5 pedicles. All
      steps of pedicle cannulation were performed under Iso-C 3D image guidance.
      RESULTS: A postoperative computed tomography scan showed accurate placement of
      all pedicle screws. The patient experienced an improvement in leg pain with no
      new neurologic deficits. CONCLUSIONS: The present case is the first case to
      demonstrate the intraoperative use of a 3D fluoroscopy-based image-guidance
      system for accurate navigation during lumbar pedicle screw placement.

PMID- 15863092
TI  - Analysis of a retrieved polyethylene total disc replacement component.
AB  - BACKGROUND CONTEXT: Although total disc replacements have been performed in
      Europe since the 1980s, this type of surgery is still new in the United States.
      The clinical performance of polyethylene in total disc replacements is still not
      well understood. PURPOSE: To describe the wear, surface damage, oxidation and
      mechanical properties in an explanted polyethylene total disc replacement
      component. STUDY DESIGN/SETTING: Case report, analysis of retrieved implant.
      PATIENT SAMPLE: Case report. OUTCOME MEASURES: Analysis of wear, oxidation and
      mechanical properties in the retrieved total disc replacement. METHODS: A 49-year
      old female patient was implanted at L5-S1 with an SB Charite total disc
      prosthesis (DePuy Spine, Raynham, MA). After 1.6 years, the patient underwent a
      posterior, instrumented fusion because of intractable low back, left buttock and
      radicular left leg pain. Preoperative diagnostics revealed loosening at the bone
      implant interface at L5 and S1, anterior migration of the L5 base plate and
      severe degeneration of the L5-S1 facet joints. The retrieved polyethylene core
      showed evidence of damage around the periphery or rim. Transverse, subsurface
      cracks in the polyethylene, which initiated near the rim and penetrated into the
      interior of the component, were imaged using thin-film optical microscopy and
      micro-computed-tomography imaging. Analysis using Fourier transform infrared
      spectroscopy (American Society for Testing and Materials [ASTM] F2102) documented
      low levels of oxidation within 1 mm of the articulating surface. Miniature
      specimen mechanical testing (ASTM F2183), conducted near the surface where the
      oxidation was greatest, demonstrated that the mechanical properties were not
      substantially degraded. CONCLUSION: In this case, the anterior revision surgery
      was difficult and potentially life-threatening. The revision strategy of an
      instrumented posterior fusion to salvage a failed SB Charite disc replacement may
      be unpredictable and, in this case, ultimately unsuccessful. Despite the small
      size of the retrieved polyethylene core, ASTM standard test techniques developed
      for analysis of retrieved hip and knee replacements were readily adapted for the
      total disc prosthesis.

PMID- 15863093
TI  - Double-antibody sandwich ELISA using biotinylated antibodies for the detection of
      Echinococcus granulosus coproantigens in dogs.
AB  - Here we present the diagnostic evaluation of an improved double-antibody sandwich
      ELISA for detecting Echinococcus granulosus antigens in dog faecal samples
      (coproantigens). A purified rabbit IgG fraction against protoscolex excretory
      secretory products was used as primary antibody, and the same fraction conjugated
      with biotin as secondary antibody. In order to validate the sandwich ELISA, intra
      and inter-assay precision, linearity, and recovery percentages were calculated.
      The diagnostic evaluation of the method was carried out by investigating faecal
      samples from 37 dogs naturally infected with E. granulosus, 15 Echinococcus-free
      dogs infected with Taenia spp., 82 dogs with non-taeniid helminths and 66 dogs
      free of helminth infections. An overall sensitivity of 78.4% and specificity of
      93.3% were determined. Positive and negative predictive values were 72 and 95%,
      respectively, and the diagnostic efficiency was 90.5%. In addition, the sandwich
      ELISA detection limit was estimated in 5.12 ng ml(-1). These results are highly
      satisfactory, allowing the use of this methodology in surveillance and control
      programs for intestinal echinococcosis in dogs.

PMID- 15863094
TI  - MT FdR: a ferredoxin reductase from M. tuberculosis that couples to MT CYP51.
AB  - We report the molecular cloning, expression and partial characterization of MT
      FdR, an FAD-associated flavoprotein, from Mycobacterium tuberculosis similar to
      the oxygenase-coupled NADH-dependent ferredoxin reductases (ONFR). We establish,
      through kinetic and spectral analysis, that MT FdR preferentially uses NADH as
      cofactor. Furthermore, MT FdR forms a complex with mycobacterial ferredoxin (MT
      Fdx) and MT CYP51, a cytochrome P450 (CYP) from M. tuberculosis that is similar
      to lanosterol 14alpha-demethylase isozymes. This reconstituted system transfers
      electrons from the cofactor to the heme iron of MT CYP51 and effects the
      demethylation of lanosterol.

PMID- 15863095
TI  - Evidence for dissociation of chlorophyll b from the main light-harvesting complex
      in the oligomerization state isolated from marine alga, Bryopsis corticulans.
AB  - We investigated the composition and organization of chlorophylls in monomers,
      trimers and oligomers (small aggregates) of the main light-harvesting complex
      (LHC II) isolated from marine alga, Bryopsis corticulans, using a combination of
      measurements with reversed-phase high performance liquid chromatography (RP-HPLC)
      and steady-state spectroscopy of absorption, circular dichroism (CD) and low
      temperature fluorescence. The composition and organization of the chlorophylls in
      monomeric and trimeric LHC II were essentially identical to those of LHC II from
      higher plants. For LHC II oligomers, a large decrease of chlorophyll (Chl) b
      absorption and of CD signals corresponding to Chl b was consistent with the
      quantitative analysis of Chl b by RP-HPLC, indicating that oligomerization of the
      LHC II proteins significantly influenced spectroscopic properties and led to the
      dissociation of Chl b molecules from LHC II. Our data strongly suggested that
      protein oligomerization constitutes a structural basis for the decrease of Chl b
      molecules in LHC II of B. corticulans. The LHC II of B. corticulans might play a
      photoprotective role with the reduction of the ability of light absorption via
      alteration of its own structural conformation.

PMID- 15863096
TI  - The transient complex of poplar plastocyanin with cytochrome f: effects of ionic
      strength and pH.
AB  - The orientation of poplar plastocyanin in the complex with turnip cytochrome f
      has been determined by rigid-body calculations using restraints from paramagnetic
      NMR measurements. The results show that poplar plastocyanin interacts with
      cytochrome f with the hydrophobic patch of plastocyanin close to the heme region
      on cytochrome f and via electrostatic interactions between the charged patches on
      both proteins. Plastocyanin is tilted relative to the orientation reported for
      spinach plastocyanin, resulting in a longer distance between iron and copper
      (13.9 A). With increasing ionic strength, from 0.01 to 0.11 M, all observed
      chemical-shift changes decrease uniformly, supporting the idea that electrostatic
      forces contribute to complex formation. There is no indication for a
      rearrangement of the transient complex in this ionic strength range, contrary to
      what had been proposed earlier on the basis of kinetic data. By decreasing the pH
      from pH 7.7 to pH 5.5, the complex is destabilized. This may be attributed to the
      protonation of the conserved acidic patches or the copper ligand His87 in poplar
      plastocyanin, which are shown to have similar pK(a) values. The results are
      interpreted in a two-step model for complex formation.

PMID- 15863097
TI  - Investigation of B-branch electron transfer by femtosecond time resolved
      spectroscopy in a Rhodobacter sphaeroides reaction centre that lacks the Q(A)
      ubiquinone.
AB  - The dynamics of electron transfer in a membrane-bound Rhodobacter sphaeroides
      reaction centre containing a combination of four mutations were investigated by
      transient absorption spectroscopy. The reaction centre, named WAAH, has a
      mutation that causes the reaction centre to assemble without a Q(A) ubiquinone
      (Ala M260 to Trp), a mutation that causes the replacement of the H(A)
      bacteriopheophytin with a bacteriochlorophyll (Leu M214 to His) and two mutations
      that remove acidic groups close to the Q(B) ubiquinone (Glu L212 to Ala and Asp
      L213 to Ala). Previous work has shown that the Q(B) ubiquinone is reduced by
      electron transfer along the so-called inactive cofactor branch (B-branch) in the
      WAAH reaction centre (M.C. Wakeham, M.G. Goodwin, C. McKibbin, M.R. Jones, Photo
      accumulation of the P(+)Q(B)(-) radical pair state in purple bacterial reaction
      centres that lack the Q(A) ubiquinone, FEBS Letters 540 (2003) 234-240). In the
      present study the dynamics of electron transfer in the membrane-bound WAAH
      reaction centre were studied by femtosecond transient absorption spectroscopy,
      and the data analysed using a compartmental model. The analysis indicates that
      the yield of Q(B) reduction via the B-branch is approximately 8% in the WAAH
      reaction centre, consistent with results from millisecond time-scale kinetic
      spectroscopy. Possible contributions to this yield of the constituent mutations
      in the WAAH reaction centre and the membrane environment of the complex are
      discussed.

PMID- 15863098
TI  - The nuclear genes encoding the internal (KlNDI1) and external (KlNDE1)
      alternative NAD(P)H:ubiquinone oxidoreductases of mitochondria from Kluyveromyces
      lactis.
AB  - Cloning, sequence and functional analyses of the Kluyveromyces lactis genes
      KlNDI1 and KlNDE1 are reported. These genes encode for proteins with high
      homology to the mitochondrial internal (Ndi1p) and external (Nde1p) alternative
      NADH:ubiquinone oxidoreductases from Saccharomyces cerevisiae and complement the
      respective mutations. Analysis of KlNDI1 transcriptional regulation showed that
      expression of this gene is lower in 2% glucose than in 0.5% glucose or non
      fermentable carbon sources. Beta-galactosidase activity values, shown by lacZ
      fusions of KlNDI1 promoter deletions, suggested that two Adr1p binding sites
      mediate this carbon source regulation of KlNDI1. The expression of the KlNDE1
      gene in S. cerevisiae mutant strains and measurement of respiration with isolated
      mitochondria showed that the protein encoded by KlNDE1 oxidizes NADPH, this being
      an important difference with respect to the conventional yeast S. cerevisiae.
      Moreover, Northern blot experiments using a phosphoglucose isomerase mutant
      showed that KlNDE1 gene transcription increases with glucose metabolism through
      the pentose phosphate pathway.

PMID- 15863099
TI  - Composition of complex I from Neurospora crassa and disruption of two "accessory"
      subunits.
AB  - Respiratory chain complex I of the fungus Neurospora crassa contains at least 39
      polypeptide subunits, of which 35 are conserved in mammals. The 11.5 kDa and 14
      kDa proteins, homologues of bovine IP15 and B16.6, respectively, are conserved
      among eukaryotes and belong to the membrane domain of the fungal enzyme. The
      corresponding genes were separately inactivated by repeat-induced point
      mutations, and null-mutant strains of the fungus were isolated. The lack of
      either subunit leads to the accumulation of distinct intermediates of the
      membrane arm of complex I. In addition, the peripheral arm of the enzyme seems to
      be formed in mutant nuo14 but, interestingly, not in mutant nuo11.5. These
      results and the analysis of enzymatic activities of mutant mitochondria indicate
      that both polypeptides are required for complex I assembly and function.

PMID- 15863100
TI  - Identification and characterisation of a new class of highly specific and potent
      inhibitors of the mitochondrial pyruvate carrier.
AB  - Two novel thiazolidine compounds, GW604714X and GW450863X, were found to be
      potent inhibitors of mitochondrial respiration supported by pyruvate but not
      other substrates. Direct measurement of pyruvate transport into rat liver and
      yeast mitochondria confirmed that these agents inhibited the mitochondrial
      pyruvate carrier (MPC) with K(i) values <0.1 muM. Inhibitor titrations of
      pyruvate-dependent respiration by heart mitochondria gave values (+/-S.E.) for
      the concentration of inhibitor binding sites (pmol per mg protein) and their K(i)
      (nM) of 56.0+/-0.9 and 0.057+/-0.010 nM for the more hydrophobic GW604714X; for
      GW450863X the values were 59.9+/-4.6 and 0.60+/-0.12 nM. [(3)H]-methoxy-GW450863X
      binding was also used to determine the MPC content of the heart, kidney, liver
      and brain mitochondria giving values of 56, 40, 26 and 20 pmol per mg protein
      respectively. Binding to yeast mitochondria was <10% of that in rat liver
      mitochondria, consistent with the slow rate of pyruvate transport into yeast
      mitochondria. [(3)H]-methoxy-GW450863X binding was inhibited by GW604714X and by
      the established MPC inhibitor, UK5099. The absorbance spectra of GW450863X and
      GW604714X were markedly changed by the addition of beta-mercaptoethanol
      suggesting that the novel inhibitors, like alpha-cyanocinnamate, possess an
      activated double bond that attacks a critical cysteine residue on the MPC.
      However, no labelled protein was detected following SDS-PAGE suggesting that the
      covalent modification is reversible. GW604714X and GW450863X inhibited l-lactate
      transport by the plasma membrane monocarboxylate transporter MCT1, but at
      concentrations more than four orders of magnitude greater than the MPC.

PMID- 15863101
TI  - The bioenergetic role of dioxygen and the terminal oxidase(s) in cyanobacteria.
AB  - Owing to the release of 13 largely or totally sequenced cyanobacterial genomes
      (see and ), it is now possible to critically assess and compare the most
      neglected aspect of cyanobacterial physiology, i.e., cyanobacterial respiration,
      also on the grounds of pure molecular biology (gene sequences). While there is
      little doubt that cyanobacteria (blue-green algae) do form the largest, most
      diversified and in both evolutionary and ecological respects most significant
      group of (micro)organisms on our earth, and that what renders our blue planet
      earth to what it is, viz. the O(2)-containing atmosphere, dates back to the
      oxygenic photosynthetic activity of primordial cyanobacteria about 3.2x10(9)
      years ago, there is still an amazing lack of knowledge on the second half of
      bioenergetic oxygen metabolism in cyanobacteria, on (aerobic) respiration. Thus,
      the purpose of this review is threefold: (1) to point out the unprecedented role
      of the cyanobacteria for maintaining the delicate steady state of our terrestrial
      biosphere and atmosphere through a major contribution to the poising of oxygenic
      photosynthesis against aerobic respiration ("the global biological oxygen
      cycle"); (2) to briefly highlight the membrane-bound electron-transport
      assemblies of respiration and photosynthesis in the unique two-membrane system of
      cyanobacteria (comprising cytoplasmic membrane and intracytoplasmic or thylakoid
      membranes, without obvious anastomoses between them); and (3) to critically
      compare the (deduced) amino acid sequences of the multitude of hypothetical
      terminal oxidases in the nine fully sequenced cyanobacterial species plus four
      additional species where at least the terminal oxidases were sequenced. These
      will then be compared with sequences of other proton-pumping haem-copper
      oxidases, with special emphasis on possible mechanisms of electron and proton
      transfer.

PMID- 15863102
TI  - Titration of E. coli transhydrogenase domain III with bound NADP+ or NADPH
      studied by NMR reveals no pH-dependent conformational change in the physiological
      pH range.
AB  - A pH-titration 2D NMR study of Escherichia coli transhydrogenase domain III with
      bound NADP(+) or NADPH has been carried out, in which the pH was varied between
      5.4 and 12. In this analysis, individual amide protons served as reporter groups.
      The apparent pK(a) values of the amide protons, determined from the pH-dependent
      chemical shift changes, were attributed to actual pK(a) values for several
      titrating residues in the protein. The essential Asp392 is shown to be protonated
      at neutral pH in both the NADP(+) and NADPH forms of domain III, but with a
      marked difference in pK(a) not only attributable to the charge difference between
      the substrates. Titrating residues found in loop D/alpha5 point to a
      conformational difference of these structural elements that is redox-dependent,
      but not pH dependent. The observed apparent pK(a) values of these residues are
      discussed in relation to the crystal structure of Rhodospirillum rubrum domain
      III, the solution structure of E. coli domain III and the mechanism of intact
      proton-translocating transhydrogenase.

PMID- 15863103
TI  - A fibril-reinforced poroviscoelastic swelling model for articular cartilage.
AB  - From a mechanical point of view, the most relevant components of articular
      cartilage are the tight and highly organized collagen network together with the
      charged proteoglycans. Due to the fixed charges of the proteoglycans, the cation
      concentration inside the tissue is higher than in the surrounding synovial fluid.
      This excess of ion particles leads to an osmotic pressure difference, which
      causes swelling of the tissue. The fibrillar collagen network resists straining
      and swelling pressures. This combination makes cartilage a unique, highly
      hydrated and pressurized tissue, enforced with a strained collagen network. Many
      theories to explain articular cartilage behavior under loading, expressed in
      computational models that either include the swelling behavior or the properties
      of the anisotropic collagen structure, can be found in the literature. The most
      common tests used to determine the mechanical quality of articular cartilage are
      those of confined compression, unconfined compression, indentation and swelling.
      All theories currently available in the literature can explain the cartilage
      response occurring in some of the above tests, but none of them can explain these
      for all of the tests. We hypothesized that a model including simultaneous
      mathematical descriptions of (1) the swelling properties due to the fixed-change
      densities of the proteoglycans and (2) the anisotropic viscoelastic collagen
      structure, can explain all these test simultaneously. To study this hypothesis we
      extended our fibril-reinforced poroviscoelastic finite element model with our
      biphasic swelling model. We have shown that the newly developed fibril-reinforced
      poroviscoelastic swelling (FPVES) model for articular cartilage can
      simultaneously account for the reaction force during swelling, confined
      compression, indentation and unconfined compression as well as the lateral
      deformation during unconfined compression. Using this theory it is possible to
      analyze the link between the collagen network and the swelling properties of
      articular cartilage.

PMID- 15863104
TI  - Articular contact at the tibiotalar joint in passive flexion.
AB  - The knowledge of the contact areas at the tibiotalar articulating surfaces during
      passive flexion is fundamental for the understanding of ankle joint mobility.
      Traditional contact area reports are limited by the invasive measuring techniques
      used and by the complicated loading conditions applied. In the present study,
      passive flexion tests were performed on three anatomical preparations from lower
      leg amputation. Roentgen Stereophotogrammetric Analysis was used to accurately
      reconstruct the position of the tibia and the talus at a number of unconstrained
      flexion positions. A large number of points was collected on the surface of the
      tibial mortise and on the trochlea tali by a 3-D digitiser. Articular surfaces
      were modelled by thin plate splines approximating these points. Relative
      positions of these surfaces in all the flexion positions were obtained from
      corresponding bone position data. A distance threshold was chosen to define
      contact areas. A consistent pattern of contact was found on the articulating
      surfaces. The area moved anteriorly on both articular surfaces with dorsiflexion.
      The average position of the contact area centroid along the tibial mortise at
      maximum plantarflexion and at maximum dorsiflexion was respectively 58% posterior
      and 40% anterior of the entire antero-posterior length. For increasing
      dorsiflexion, the contact area moved from medial to lateral in all the specimens.

PMID- 15863105
TI  - In vivo passive mechanical properties of the human gastrocnemius muscle belly.
AB  - The purpose of the present study was to determine the in vivo passive mechanical
      properties, including the length below the slack length, of the gastrocnemius
      muscle (GAS) belly in humans. Transverse ultrasound images of the medial head of
      the GAS were taken in 11 subjects during passive knee extension from 80 degrees
      to 5 degrees with a constant ankle joint angle of 10 degrees (0 degrees is the
      neutral ankle position: positive values for dorsiflexion). The change in passive
      ankle joint moment (Mp), which is produced only by the GAS length change, was
      also measured during passive knee extension. The onset of Mp during passive knee
      extension was found to be 43+/-8 degrees (mean+/-SD) when the baseline of the Mp
      was set at the average Mp in the range of 55-60 degrees where the Mp was almost
      constant (SD<0.03 Nm). At this onset, the muscle fascicle length of the GAS (Lf)
      was 46+/-7 mm (slack length; Lfs). Lf at 80 degrees was 6+/-4 mm (13+/-6%) less
      than the Lfs, and Lf at 5 degrees was 12+/-5 mm (27+/-11%) greater than the Lfs.
      The passive force-resisting compression of the GAS did not produce a dorsiflexion
      moment in the joint angle range adopted. The passive ankle joint moment increased
      linearly with Lf (coefficient of determination (R2)=0.85-0.96), and the slopes of
      the relationships between Lf and Mp, and between the relative Lf to Lfs and Mp
      were 0.093+/-0.038 Nm/mm and 0.043+/-0.021 Nm/%Lfs. The findings of the present
      study can be implemented in musculoskeletal modeling, which would provide a more
      accurate evaluation of the passive mechanical properties of muscle during
      movement.

PMID- 15863106
TI  - Finite element analysis of covered microstents.
AB  - Currently available neuroendovascular devices are inadequate for effective
      treatment of many wide-necked or fusiform intracranial aneurysms and intracranial
      carotid-cavernous fistulae (CCF). Placing a covered microstent across the
      intracranial aneurysm neck and CCF rent could restore normal vessel morphology by
      preventing blood flow into the aneurysm lumen or CCF rent. To fabricate covered
      microstents, our research group has developed highly flexible ultra thin
      (approximately 150 microm) silicone coverings and elastomerically captured them
      onto commercially available metal stents without stitching. Preliminary in vivo
      studies were conducted by placing these covered microstents in the common carotid
      artery of rabbits. The feasibility of using covered stents was demonstrated.
      However, the cover affected the deployment pressure and the stents failed
      occasionally during deployment due to tearing of the cover. Appropriate modeling
      of covered stents will assist in designing suitable coverings, and help to reduce
      the failure rate of covered microstents. The purpose of this study is to use the
      finite element method to determine the mechanical properties of the covered
      microstent and investigate the effects of the covering on the mechanical behavior
      of the covered microstent. Variations in the mechanical properties of the covered
      microstent such as deployment pressure, elastic recoil and longitudinal
      shortening due to change in thickness and material properties of the cover have
      been investigated. This work is also important for custom design of covered
      microstents such as adding cutout holes to save adjacent perforating arteries.

PMID- 15863107
TI  - Interrelationship of trabecular mechanical and microstructural properties in
      sheep trabecular bone.
AB  - The ability to evaluate fracture risk at an early time point is essential for
      improved prognostics as well as enhanced treatment in cases of bone loss such as
      from osteoporosis. Improving the diagnostic ability is inherent upon both high
      resolution non-invasive imaging, and a thorough understanding of how the derived
      indices of structure and density relate to its true mechanical behavior. Using
      sheep femoral trabecular bone with a range of strength, the interrelationship of
      mechanical and microstructural parameters was analyzed using multi-directional
      mechanical testing and micro-computed tomography. Forty-five cubic trabecular
      bone samples were harvested from 23 adult female sheep, some of whom had received
      hind-limb vibratory stimuli over the course of 2 years with consequently enhanced
      mechanical properties. These samples were pooled into a low, medium, or high
      strength group for further analysis. The findings show that microCT indices that
      are structural in nature, e.g., structural model index (SMI) (r2=0.85, p<0.0001)
      is as good as more density oriented indices like bone volume/total volume (BV/TV)
      (r2=0.81, p<0.0001) in predicting the ultimate strength of a region of trabecular
      bone. Additionally, those indices more related to global changes in trabecular
      structure such as connectivity density (ConnD) or degree of anisotropy (DA) are
      less able to predict the mechanical properties of bone. Interrelationships of
      trabecular indices such as trabecular number (TbN), thickness (TbTh), and spacing
      (TbSp) provide clues as to how the trabecular bone will remodel to ultimately
      achieve differences in the apparent mechanical properties. For instance, the
      analysis showed that a loss of bone primarily affects the connectedness and
      overall number of trabeculae, while increased strength results in an increase of
      the overall thickness of trabeculae while not improving the connectedness.
      Certainly, the microCT indices studied are able to predict the bulk mechanical
      properties of a trabecular ROI well, leaving unaccounted only about 15-20% of its
      inherent variability. Diagnostically, this implies that future work on the early
      prediction of fracture risk should continue to explore the role of bone quality
      as the key factors or as an adjuvant to bone quantity (e.g., apparent density).

PMID- 15863108
TI  - Lordotic vertebrae in sea bass (Dicentrarchus labrax L.) are adapted to increased
      loads.
AB  - Lordosis in fish is an abnormal ventral curvature of the vertebral column,
      accompanied by abnormal calcification of the afflicted vertebrae. Incidences of
      lordosis are a major problem in aquaculture and often correlate with increased
      swimming activity. To understand the biomechanical causes and consequences of
      lordosis, we mapped the morphological changes that occur in the vertebrae of
      European sea bass during their development from larva to juvenile. Our micro-CT
      analysis of lordotic and non-lordotic vertebrae revealed significant differences
      in their micro-architecture. Lordotic vertebrae have a larger bone volume,
      flattened dorsal zygapophyses and extra lateral ridges. They also have a larger
      second moment of area (both lateral and dorso-ventral) than non-lordotic
      vertebrae. This morphology suggests lordotic vertebrae to be adapted to an
      increased bending moment, caused by the axial musculature during increased
      swimming activity. We hypothesize the increase in swimming activity to have a two
      fold effect in animals that become lordotic. The first effect is buckling failure
      of the axial skeleton due to an increased compressive load. The second effect is
      extra bone deposition as an adaptive response of the vertebrae at the cellular
      level, caused by an increased strain and strain rate in these vertebrae. Lordosis
      thus comprises both a buckling failure of the vertebral column and a molecular
      response that adapts the lordotic vertebrae to a new loading regime.

PMID- 15863109
TI  - A high-frequency lung injury mechanism in blunt thoracic impact.
AB  - When a mechanical load is applied very rapidly to the thoracic wall, part of the
      internal damage is suspected to be due to a "high-frequency" injury mechanism,
      that is, a phenomenon in which waves are involved. This paper addresses a
      specific high-frequency mechanism for lung injury in which a stress wave is
      generated through rapid acceleration of the body wall. Displacement-related
      injuries, which are rather "low-frequency" phenomena, are not considered. The
      present work was done in the context of assessing behind armor blunt trauma
      (injury to thoracic organs occurring when a bullet is stopped by a body armor)
      through mathematical modeling. One aspect of the thorax response to high-speed
      blunt impact and an associated injury mechanism are investigated based on an
      idealized model of thorax and a set of computations presented in previous papers.
      The injury mechanism considered elucidates a possible mathematical relationship
      between the acceleration at the surface of the thoracic wall and the occurrence
      of lung injury.

PMID- 15863110
TI  - Effects of a sustained extension on arterial growth and remodeling: a theoretical
      study.
AB  - Three recent studies reveal that the unloaded length of a carotid artery
      increases significantly and rapidly in response to sustained increases in axial
      extension. Moreover, such lengthening involves an "unprecedented" increase in the
      rate of turnover of cells and matrix. Although current data are not sufficient
      for detailed biomechanical analyses, we present general numerical simulations
      that are consistent with the reported observations and support the hypothesis
      that rates of turnover correlate with the extent that stresses are perturbed from
      normal. In particular, a 3-D analysis of wall stress suggests that moderate (15%)
      increases in axial extension can increase the axial stress to a much greater
      extent than marked (50%) increases in blood pressure increase the circumferential
      stress. Furthermore, such increases in axial stress can occur without inducing
      significant gradients in stress within the wall. Consequently, we use a new, 2-D
      constrained mixture model to study evolving changes in the geometry, structure,
      and properties of carotid arteries in response to a sustained increase in axial
      extension. These simulations are qualitatively similar to the reports in the
      literature and support the notion that the stress-free lengths of individual
      constituents evolve during growth and remodeling.

PMID- 15863111
TI  - Ability of static and statistical mechanics posturographic measures to
      distinguish between age and fall risk.
AB  - Traditional posturographic analysis and four statistical mechanics techniques
      were applied to center-of-pressure (COP) trajectories of young, older "low-fall
      risk" and older "high-fall-risk" individuals. Low-fall-risk older adults were
      active 3 days per week in a cardiac rehabilitation program, while high-fall-risk
      older adults were diagnosed with perilymph fistula. Subjects diagnosed with
      perilymph fistula must have experienced two of the following vestibular findings:
      constant disequilibrium, positional vertigo and/or a positive fistula test. Non
      parametric statistical tests were used to determine whether the posturographic
      measures could detect differences between the young and older "low-fall-risk"
      groups (age comparison) and between the older "low-" and "high-risk" groups (risk
      of falling comparison). The statistical mechanics techniques were more sensitive
      than the traditional measures: detecting significant differences between the
      young and older "low-risk" groups, while none of the traditional measures were
      significantly different. In addition, interpretation of the statistical mechanics
      techniques may offer more insight into the nature of the process controlling the
      COP trajectories. However, the methods offered slightly different explanations.
      For instance, the Hurst rescaled range analysis suggests that the movement of the
      COP is governed solely by anti-persistent behavior, whereas the stabilogram
      diffusion analysis suggests a short-term persistence balanced by a long-term anti
      persistence. These discrepancies highlight the need for a model that incorporates
      the biological systems responsible for maintaining balance and experimental
      methods to directly quantify their status and roles. Until such a model exists,
      however, the statistical mechanics techniques appear to have some advantages over
      traditional posturographic measures for studying balance control.

PMID- 15863112
TI  - Dynamic osmotic loading of chondrocytes using a novel microfluidic device.
AB  - Many cells exhibit disparate responses to a mechanical stimulus depending on
      whether it is applied dynamically or statically. In this context, few studies
      have examined how cells respond to dynamic changes of the extracellular
      osmolality. In this study, we hypothesized that the cell size change response of
      cultured articular chondrocytes would be dependent on the frequency of applied
      osmotic loading. To test this hypothesis, we developed a novel microfluidic
      device, to apply hydrostatic pressure-driven dynamic osmotic loading by applying
      composition modulated flow, adapted from Tang and co-workers. This microfluidic
      device was used to study osmotic loads of +/-180 mOsm at a frequency up to 0.1 Hz
      with a constant minimal fluid-shear stress, and permit real-time monitoring of
      cell responses. Bovine articular chondrocytes were observed to exhibit increasing
      changes in cell volume with decreasing osmotic loading frequency. When the cell
      volume response was modeled by an exponential function, chondrocytes exhibited
      significantly different volume change responses to dynamic osmotic loading at
      0.0125 Hz and static osmotic loading applied for a period of four minutes (Delta
      = +/-180 mOsm relative to the isotonic 360 mOsm). The intracellular calcium
      response at 0.0125 Hz was also monitored and compared with the response to static
      loading. Coupled with phenomenological or constitutive models, this novel
      approach could yield new information regarding cell material properties in
      response to dynamic loading that may contribute new insights into mechanisms of
      cellular homeostasis and mechanotransduction.

PMID- 15863113
TI  - Combined effects of pulsatile flow and dynamic curvature on wall shear stress in
      a coronary artery bifurcation model.
AB  - A three-dimensional model with simplified geometry for the branched coronary
      artery is presented. The bifurcation is defined by an analytical intersection of
      two cylindrical tubes lying on a sphere that represents an idealized heart
      surface. The model takes into account the repetitive variation of curvature and
      motion to which the vessel is subject during each cardiac cycle, and also
      includes the phase difference between arterial motion and blood flowrate, which
      may be nonzero for patients with pathologies such as aortic regurgitation. An
      arbitrary Lagrangian Eulerian (ALE) formulation of the unsteady, incompressible,
      three-dimensional Navier-Stokes equations is employed to solve for the flow
      field, and numerical simulations are performed using the spectral/hp element
      method. The results indicate that the combined effect of pulsatile inflow and
      dynamic geometry depends strongly on the aforementioned phase difference.
      Specifically, the main findings of this work show that the time-variation of
      flowrate ratio between the two branches is minimal (less than 5%) for the
      simulation with phase difference angle equal to 90 degrees, and maximal (51%) for
      270 degrees. In two flow pulsatile simulation cases for fixed geometry and
      dynamic geometry with phase angle 270 degrees, there is a local minimum of the
      normalized wall shear rate amplitude in the vicinity of the bifurcation, while in
      other simulations a local maximum is observed.

PMID- 15863114
TI  - Multi-functionality of the cat medical gastrocnemius during locomotion.
AB  - The functional role of biarticular muscles was investigated based on direct force
      measurement in the cat medial gastrocnemius (MG) and analysis of hindlimb
      kinematics and kinetics for the stance phase of level, uphill, and downhill
      walking. Four primary functional roles of biarticular muscles have been proposed
      in the past. These functional roles have typically been discussed independently
      of each other, and biarticular muscles have rarely been assigned more than one
      functional roles for different phases of the work cycle. The purpose of this
      study was to elucidate the functional role of the biarticular cat MG during
      locomotion. It was found that MG forces were primarily associated with the moment
      requirements at the ankle for most of the stance phase, but also helped to
      satisfy the moments at the knee in the initial phase of stance. In the second
      half of stance, MG transferred mechanical energy from the knee to the ankle from
      the knee to the ankle, while simultaneously producing a substantial amount of
      mechanical work. Based on these results, we hypothesize that MG's primary
      function is that of an ankle extensor. However, because of the coupling of the
      ankle extensor moment with a knee flexor moment in the initial, and a knee
      extensor moment in the final phase of stance, MG satisfies two joint moments in
      early stance, and transfers mechanical energy from the knee to the ankle in late
      stance. We conclude that cat MG has multiple functional roles during the stance
      phase of locomotion, and speculate that such multi-functionality also exists in
      other bi- and multi-articular muscles.

PMID- 15863115
TI  - Analytical modeling of the instantaneous pressure gradient across the aortic
      valve.
AB  - Aortic stenosis is the most frequent valvular heart disease. The mean systolic
      value of the transvalvular pressure gradient (TPG) is commonly utilized during
      clinical examination to evaluate its severity and it can be determined either by
      cardiac catheterization or by Doppler echocardiography. TPG is highly time
      dependent over systole and is known to depend upon the transvalvular flow rate,
      the effective orifice area (EOA) of the aortic valve and the cross-sectional area
      of the ascending aorta. However it is still unclear how these parameters modify
      the TPG waveform. We thus derived a simple analytical model from the energy loss
      concept to describe the instantaneous TPG across the aortic valve during systole.
      This theoretical model was validated with orifice plates and bioprosthetic heart
      valves in an in vitro aortic flow model. Instantaneous TPG was measured by
      catheter and its waveform was compared with the one determined from the
      transvalvular flow rate, the valvular EOA and the aortic cross-sectional area,
      using the derived equation. Our results showed a very good concordance between
      the measured and predicted instantaneous TPG. The analytical model proposed and
      validated in this study provides a comprehensive description of the aortic valve
      hemodynamics that can be used to accurately predict the instantaneous
      transvalvular pressure gradient in native and bioprosthetic aortic valves. The
      consideration of this model suggests that: (1) TPG waveform is exclusively
      dependent upon transvalvular flow rate and flow geometry, (2) the frequently
      applied simplified Bernoulli equation may overestimate mean TPG by more than 30%
      and (3) the measurement of ejection time by cardiac catheterization may
      underestimate the actual ejection time, especially in patients with mild/moderate
      aortic stenosis and low cardiac output.

PMID- 15863116
TI  - Effects of abnormal posture on capsular ligament elongations in a computational
      model subjected to whiplash loading.
AB  - Although considerable biomechanical investigations have been conducted to
      understand the response of the cervical spine under whiplash (rear impact-induced
      postero-anterior loading to the thorax), studies delineating the effects of
      initial spinal curvature are limited. This study advanced the hypothesis that
      abnormal curvatures (straight or kyphotic) of the cervical column affect spinal
      kinematics during whiplash loading. Specifically, compared to the normal lordotic
      curvature, abnormal curvatures altered facet joint ligament elongations. The
      quantifications of these elongations were accomplished using a validated
      mathematical model of the human head-neck complex that simulated three
      curvatures. The model was validated using companion experiments conducted in our
      laboratory that provided facet joint kinematics as a function of cervical spinal
      level. Regional facet joint ligament elongations were investigated as a function
      of whiplash loading in the four local anatomic regions of each joint. Under the
      normal posture, greatest elongations occurred in the dorsal anatomic region at
      the C2-C3 level and in the lateral anatomic region from C3-C4 to C6-C7 levels.
      Abnormal postures increased elongation magnitudes in these regions by up to 70%.
      Excessive ligament elongations induce laxity to the facet joint, particularly at
      the local regions of the anatomy in the abnormal kyphotic posture. Increased
      laxity may predispose the cervical spine to accelerated degenerative changes over
      time and lead to instability. Results from the present study, while providing
      quantified level- and region-specific kinematic data, concur with clinical
      findings that abnormal spinal curvatures enhance the likelihood of whiplash
      injury and may have long-term clinical and biomechanical implications.

PMID- 15863117
TI  - Bicycle seat interface pressure: reliability, validity, and influence of hand
      position and workload.
AB  - Bicycle seat pressure is often examined by researchers exploring solutions for
      reducing seat injuries as it is thought a critical determinant; however, a
      reliable and valid methodology for this undertaking has not been reported. The
      current study was designed to address this shortcoming and to establish baseline
      interface pressure measurements for females and males. Participants completed two
      separate identical bicycle ergometer trials at 118 W in the tops and drops and at
      300+/-82.4 W in top handlebar positions. Seat pressures were quantified from a
      pressure-sensing mat and the validity of the pressure system was examined through
      the relationship between known seat weights and the sum of seat pressures. Within
      trial intraclass correlation coefficients (ICCs) ranged between 0.90 and 0.99 and
      the between trial ICC values ranged between 0.02 and 0.96. The relationship
      (Pearson correlation coefficient) between seat weight and the sum of pressures
      was 0.97. Significant peak pressures were 39% greater in the 118 W top than 300 W
      top handlebar condition and 29% greater than the 118 W drop handlebar condition
      (p < 0.05). The gender comparison revealed that significant male peak pressure
      values were greater (24%) and that female values were less influenced by the hand
      position factor. Select within trial pressure measurements were found to be
      reliable during pedaling and valid statically. Additionally, the results
      indicated that workrate and hand position were factors influencing seat pressure
      and that males and females responded differently to adjustments of these factors.

PMID- 15863118
TI  - A new method for measuring passive length-tension properties of human
      gastrocnemius muscle in vivo.
AB  - The study of muscle growth and muscle length adaptations requires measurement of
      passive length-tension properties of individual muscles, but until now such
      measurements have only been made in animal muscles. We describe a new method for
      measuring passive length-tension properties of human gastrocnemius muscles in
      vivo. Passive ankle torque and ankle angle data were obtained as the ankle was
      rotated through its full range with the knee in a range of positions. To extract
      gastrocnemius passive length-tension curves from passive torque-angle data it was
      assumed that passive ankle torque was the sum of torque due to structures which
      crossed only the ankle joint (this torque was a 6-parameter function of ankle
      joint angle) and a torque due to the gastrocnemius muscle (a 3-parameter function
      of knee and ankle angle). Parameter values were estimated with non-linear
      regression and used to reconstruct passive length-tension curves of the
      gastrocnemius. The reliability of the method was examined in 11 subjects by
      comparing three sets of measurements: two on the same day and the other at least
      a week later. Length-tension curves were reproducible: the average root mean
      square error was 5.1+/-1.1 N for pairs of measurements taken within a day and
      7.3+/-1.2 N for pairs of measurements taken at least a week apart (about 3% and
      6% of maximal passive tension, respectively). Length-tension curves were
      sensitive to mis-specification of moment arms, but changes in length-tension
      curves were not. The new method enables reliable measurement of passive length
      tension properties of human gastrocnemius in vivo, and is likely to be useful for
      investigation of changes in length-tension curves over time.

PMID- 15863119
TI  - Effects of enzymatic degradation on the frictional response of articular
      cartilage in stress relaxation.
AB  - It was recently shown experimentally that the friction coefficient of articular
      cartilage correlates with the interstitial fluid pressurization, supporting the
      hypothesis that interstitial water pressurization plays a fundamental role in the
      frictional response by supporting most of the load during the early time
      response. A recent study showed that enzymatic treatment with chondroitinase ABC
      causes a decrease in the maximum fluid load support of bovine articular cartilage
      in unconfined compression. The hypothesis of this study is that treatment with
      chondroitinase ABC will increase the friction coefficient of articular cartilage
      in stress relaxation. Articular cartilage samples (n = 34) harvested from the
      femoral condyles of five bovine knee joints (1-3 months old) were tested in
      unconfined compression with simultaneous continuous sliding (+/-1.5 mm at 1 mm/s)
      under stress relaxation. Results showed a significantly higher minimum friction
      coefficient in specimens treated with 0.1 micro/ml of chondroitinase ABC for 24 h
      (micro(min) = 0.082+/-0.024) compared to control specimens (micro(min) = 0.047+/
      0.014). Treated samples also exhibited higher equilibrium friction coefficient
      (micro(eq) = 0.232+/-0.049) than control samples (micro(eq) = 0.184+/-0.036),
      which suggest that the frictional response is greatly influenced by the degree of
      tissue degradation. The fluid load support was predicted from theory, and the
      maximum value (as a percentage of the total applied load) was lower in treated
      specimens (77+/-12%) than in control specimens (85+/-6%). Based on earlier
      findings, the increase in the ratio micro(min)/micro(eq) may be attributed to the
      decrease in fluid load support.

PMID- 15863120
TI  - Assessment of wavelet analysis of gait in children with typical development and
      cerebral palsy.
AB  - The objective of this study was to examine the use of the continuous wavelet
      transform (CWT) on surface electromyographic (sEMG) signals acquired from the
      lower extremity muscles during gait in children with typical development (TD) and
      cerebral palsy (CP). This was done to explore the possibility of developing a
      quantitative assessment scale of motor function based on time-frequency
      information. An initial study was conducted on retrospective gait data from three
      children, matched in gender and in anthropometric variables but with differing
      levels of walking ability. EMG data were extracted from five lower extremity
      muscles to assess the degrees of differentiation. The data were processed using
      the CWT to derive an average scalogram, from which the instantaneous mean
      frequency (IMNF) was calculated. Principal component analysis was used to assess
      the differences between the curves. Preliminary results indicated that for select
      lower extremity muscles, there was a significant deviation in the IMNF curves in
      the child with CP as compared to the child with TD. Furthermore, as motor
      impairment increased, total percent explained variance to the TD curves
      decreased. This suggests that it might be possible to derive a physiologically
      based quantitative index for assessing motor function and for assessing clinical
      treatments in CP using the wavelet analysis.

PMID- 15863121
TI  - Bi-directional mechanical properties of the posterior region of the glenohumeral
      capsule.
AB  - The objective of this study was to determine the mechanical properties of the
      posterior region of the glenohumeral capsule in the directions perpendicular
      (transverse) and parallel (longitudinal) to the longitudinal axis of the
      posterior band of the inferior glenohumeral ligament. A punch was used to excise
      one transverse and one longitudinal tissue sample from the posterior capsule of
      11 cadaveric shoulders. All tissue samples exhibited the typical nonlinear
      behavior reported for ligaments and tendons. Significant differences (p < 0.05)
      were detected between the transverse and longitudinal tissue samples for ultimate
      stress (1.5+/-1.4 and 4.9+/-2.9 MPa, respectively) and tangent modulus (10.3+/
      6.6 and 31.5+/-12.7 MPa, respectively). No significant differences (p > 0.05)
      were observed between the ultimate strain (transverse: 22.3+/-12.5%,
      longitudinal: 22.8+/-11.1%) and strain energy density (transverse: 27.2+/-52.8
      MPa, longitudinal: 67.5+/-88.2 MPa) of the transverse and longitudinal tissue
      samples. The ratio of the longitudinal to transverse moduli (4.8+/-4.2) was
      similar to that found for the axillary pouch (3.3+/-2.8) in a previous study.
      Thus, both the axillary pouch and the posterior capsule function to stabilize the
      joint multi-axially. Future analytical models of the glenohumeral joint should
      consider the properties of the posterior capsule in its transverse and
      longitudinal directions to fully describe the behavior of the glenohumeral
      capsule. These models will be clinically important by providing a more accurate
      representation of the intact capsule as well as simulated capsular injuries and
      surgical repair procedures.

PMID- 15863122
TI  - Quality of life in cervix cancer survivors--what matters the most in the long
      term?

PMID- 15863123
TI  - Quality of life in long-term cervical cancer survivors.
AB  - OBJECTIVES: To describe the quality of life (QOL) and long-term psychosocial
      sequelae of women of childbearing age diagnosed with cervical cancer 5-10 years
      earlier. METHODS: Utilizing a cross-sectional descriptive design, 51 cervical
      cancer survivors and 50 age-matched controls completed a comprehensive QOL
      interview. RESULTS: Participants were predominantly married, non-Hispanic White,
      with a mean age at diagnosis of 37 years and a mean age at interview of 45 years.
      This disease-free sample enjoys a good QOL, with physical, social, and emotional
      functioning comparable to or better than comparative norms. However, certain
      psychological survivorship sequelae and reproductive concerns persist.
      Participants reporting good QOL were less likely to report ongoing coping efforts
      related to having had this illness and were more likely to report greater social
      support, greater sexual pleasure, and less cervical cancer-specific distress. In
      a multiple-regression model, cancer-specific distress, spiritual well-being,
      maladaptive coping, and reproductive concerns accounted for 72% of the variance
      in QOL scores. Fifty-nine percent of respondents expressed that they would likely
      participate in a counseling program today to discuss psychosocial issues raised
      by having had cervical cancer, and 69% stated that they would have attended a
      support group program during the initial treatment if it had been offered.
      CONCLUSIONS: This information provides insight into the complex survivorship
      relationships between QOL and sequelae of cervical cancer for women diagnosed
      during childbearing years. Therefore, it is important for health care
      professionals to recognize that aspects of cancer survivorship continue to
      require attention and possible follow-up care.

PMID- 15863124
TI  - Hysterectomy with or without unilateral oophorectomy and risk of ovarian cancer.
AB  - OBJECTIVE: To analyze the role of hysterectomy, performed on benign indications,
      on the risk of developing ovarian cancer. METHODS: Multicenter case-control study
      conducted in four Italian areas. Cases were 1031 women with epithelial ovarian
      cancer. Controls were 2411 women admitted to the same network of hospitals for a
      wide spectrum of acute non-neoplastic conditions, unrelated to known risk factors
      for ovarian cancer. RESULTS: Compared to women with intact uterus and ovaries,
      the multivariate odds ratios (OR) was 0.6 (95% confidence interval 0.4-0.9) for
      women who reported hysterectomy. The OR was 0.5 > or =15 years after surgery. The
      OR was similar for women who had had pelvic surgery before age 45 and for those
      who had surgery later. No appreciable heterogeneity emerged across strata of
      parity and family history of ovarian/breast cancer. CONCLUSION: Women who had
      undergone hysterectomy had a long-term reduced risk of epithelial ovarian cancer.

PMID- 15863125
TI  - Effusion cytodiagnosis of carcinosarcoma derived from the female genital tract:
      immunohistochemical features of MMP-7 and Ki-67 and immunofluorescence double
      staining analyses of eight cases.
AB  - OBJECTIVE: Expression of Matrix metalloproteinase 7 (MMP-7) and Ki-67 by
      carcinoma components (CCs) and sarcoma components (SCs) in carcinosarcoma of the
      female reproductive organs has been investigated by conventional methods, but
      analysis with immunohistochemical staining of multiple antigens has not been
      reported. We report the profiles of expression of MMP-7 and Ki-67 in
      carcinosarcoma determined with immunohistochemical staining techniques. METHODS:
      We used antibodies against epithelial antigen (EA), epithelial membrane antigen
      (EMA), and vimentin for immunofluorescence double staining of ascitic fluid in
      eight cases of carcinosarcoma of female reproductive organs. We also used
      immunohistochemical triple staining to compare MMP-7 and Ki-67 expression between
      CCs and SCs in the primary site of carcinosarcoma. RESULTS: Immunofluorescence
      analysis revealed that all neoplastic cells in the ascitic fluid were positive
      for EA or EMA, indicating that these cells were CCs. Immunohistochemical analyses
      of the primary organ of carcinosarcoma revealed that MMP-7 was expressed on CCs
      in four of eight cases of carcinosarcoma, whereas MMP-7 was not expressed on SCs.
      The average Ki-67 labeling index (LI) in CCs and SCs was 51.8% and 28.6%,
      respectively. The difference in Ki-67 LI between CCs and SCs was statistically
      significant (t test for paired samples, P = 0.0173). CONCLUSIONS: This is the
      first study to examine carcinosarcoma of the female reproductive organ by
      immunohistochemical staining for multiple antigens, which allows analysis of
      mixed tumor elements. In addition, we found that expression of MMP-7 and the
      average Ki-67 LI differ between CCs and SCs in carcinosarcoma. The predominance
      of CCs as the malignant cells in the ascitic fluid may be due to cytological
      differences between CCs and SCs of carcinosarcoma.

PMID- 15863126
TI  - Abnormal distribution of E-cadherin and beta-catenin in different histologic
      types of cancer of the uterine cervix.
AB  - OBJECTIVE: The goal of this study was to analyze the cellular distribution and
      possible alterations of beta-catenin and E-cadherin proteins in different
      histologic types of uterine cervical cancer and precursor lesions, compared to
      normal controls. METHODS: We performed an immunochemical staining analysis of the
      cellular distribution of beta-catenin and E-cadherin proteins in biopsy samples
      from 20 normal exocervical squamous epithelium, 43 premalignant lesions, and a
      large series of 126 invasive tumors of different histologic types that included
      68 squamous carcinomas, 31 adenosquamous carcinomas, and 27 adenocarcinomas.
      Statistical significance was evaluated by the chi-square or Fisher's Exact test.
      RESULTS: We observed beta-catenin abnormally distributed in the cytoplasm of 62%
      of premalignant lesions and more than 70% of invasive cancers, statistically
      significant when compared with normal tissue (P < 0.05). Similarly, we found that
      E-cadherin exhibit a significant abnormal distribution in the cytoplasm of 58% of
      premalignant lesions (P < 0.05) and in more than 71% of squamous carcinoma and
      adenosquamous carcinoma when compared with normal tissue (P < 0.05). We found no
      differences in the distribution of E-cadherin between adenocarcinomas compared
      with control samples. Interestingly, we found that both, beta-catenin and E
      cadherin, were absent in the membrane of nearly 40% premalignant lesions. Nuclear
      staining of beta-catenin was rarely seen in any cases, contrary to what has been
      reported for this and other neoplasias. CONCLUSION: Our findings indicate that
      cellular alterations of both beta-catenin and E-cadherin are frequent in tumors
      of the uterine cervix of different histologic types, and support a role for these
      proteins in cervical cancer development.

PMID- 15863127
TI  - Cyclooxygenase-2 and c-erbB-2 expression in uterine cervical neoplasm assessed
      using tissue microarrays.
AB  - OBJECTIVES: Cyclooxygenase-2 (COX-2) and c-erbB-2 are involved in the
      pathogenesis of solid organ tumors. Chemotherapeutic agents targeting COX-2 and c
      erbB-2 are used to treat colon and breast cancers. This study evaluated the
      significance and relationship of COX-2 and c-erbB-2 protein expression in
      untreated uterine cervical neoplasm. METHODS: This study included 332 patients
      with uterine cervical neoplasm. We constructed tissue microarray blocks that
      included two cores from each donor tumor and immunostained them with primary anti
      cyclooxygenase-2 and anti-c-erbB-2 monoclonal antibodies. The clinical features
      and survival data were compared. RESULTS: Three hundred and eighteen tumor
      samples (95.8%) could be interpreted after immunohistochemical staining. COX-2
      protein expression was noted in 140 cases of uterine cervical neoplasm (44.0%):
      In 26.7% of the cervical intraepithelial neoplasia III (16/60 cases), 37.9% of
      the microinvasive squamous cell carcinoma (39/103 cases), 51.6% of the invasive
      squamous cell carcinoma (64/124 cases), and 76.2% of the adenocarcinomas (16/21
      cases) (P < 0.005). By contrast, except for one case of adenoid cystic carcinoma,
      none of the uterine cervical neoplasm expressed c-erbB-2 protein. COX-2 protein
      expression correlated with histology (P < 0.005) and stage (P < 0.05), but was
      not associated with patient survival. CONCLUSION: COX-2 may participate in the
      progression of cervical squamous cell lesions, while the contribution of c-erbB-2
      to cervical carcinogenesis is probably small.

PMID- 15863128
TI  - The expression of MAGE and GAGE genes in uterine cervical carcinoma of Korea by
      RT-PCR with common primers.
AB  - BACKGROUND: Melanoma antigen genes (MAGE) and GAGE genes are encoded by genes
      that are silent in virtually all normal adult tissues but are expressed in tumors
      from various tissues. These gene products are targets for specific immunotherapy
      as they are presented by HLA I molecules and recognized by autologous cytotoxic T
      lymphocytes. However, the characteristics of these genes, especially in uterine
      cervical cancer are relatively unknown. PURPOSE: This study evaluated the
      prevalence of MAGE and GAGE by reverse transcription-polymerase chain reaction
      (RT-PCR) with common primers and discusses clinical implications in cervical
      carcinoma. MATERIALS AND METHODS: Fresh tissue from 37 cases of primary squamous
      cell carcinoma and normal cervical mucosa were evaluated for clinicopathologic
      parameters including Human Papilloma Virus (HPV)-16,18 infection by PCR, tumor
      stage by FIGO classification and lymph node involvement. RT-nested PCR for the
      MAGE and GAGE genes was performed with common primers and DNA sequencing after
      subcloning was used for identification of PCR products of MAGE. Formalin-fixed
      paraffin embedded material from the same specimen was analyzed by in situ RT-PCR
      for MAGE. RESULTS: Expression of MAGE and GAGE was not observed in normal
      tissues. Eleven out of 37 cases expressed MAGE mRNA (29.7%): analysis of subtypes
      identified one case of MAGE-1, two cases of MAGE-4b, six cases of MAGE-3, and two
      unknown subtypes. Thirteen out of 37 cases (35.1%) expressed GAGE mRNA. No
      significant relationships between expression of these genes and FIGO staging,
      lymph node metastasis or HPV infection were found. CONCLUSION: Expression of MAGE
      and GAGE may be involved in the development of uterine cervical carcinoma from
      intraepithelial neoplasia, although without distinct prognostic significance.
      MAGE and GAGE genes have the potential to be used as targets for the treatment of
      uterine cervical carcinoma.

PMID- 15863129
TI  - Comparative genomic hybridization in four angiosarcomas of the female breast.
AB  - OBJECTIVE: Angiosarcomas represent a heterogeneous group of malignant vascular
      tumors occurring in different anatomic sites. In the female breast, they account
      for less than 1% of all malignant tumors and mainly develop as secondary
      angiosarcomas after prior irradiation. Data on cytogenetic findings in
      angiosarcomas are scarce and up to now no characteristic primary aberrations have
      been established. We herein add molecular cytogenetic findings in another 4
      angiosarcomas to 11 previously reported cases. METHODS: We investigated four
      angiosarcomas of the female breast (three primary angiosarcomas and one secondary
      tumor after irradiation for breast cancer) for DNA copy number changes using
      comparative genomic hybridization (CGH). RESULTS: All angiosarcomas revealed
      aberrant karyotypes including multiple DNA copy number changes involving various
      chromosomes. Recurrent DNA copy number changes that occurred in at least two
      cases included gains at 1q, 7p, 7q, and 8q, as well as losses at 5q and 16q.
      CONCLUSIONS: Angiosarcoma of the female breast represents a genetically
      heterogeneous tumor entity without a readily identifiable pattern of common
      chromosomal alterations. However, reviewing the cytogenetic literature on
      angiosarcomas of different sites, gains at 8q and 20p appear to emerge as the
      most frequent aberrations in at least a subset of these tumors.

PMID- 15863130
TI  - Sensitivity to Fas-mediated apoptosis in high-risk HPV-positive human cervical
      cancer cells: relationship with Fas, caspase-8, and Bid.
AB  - OBJECTIVE: Binding of Fas ligand or agonistic anti-Fas antibody to the death
      receptor Fas can activate a caspase-cascade resulting in apoptosis. In the
      present study, the functionality of the Fas pathway was studied in human cervical
      cancer cells with different HPV and p53 status. METHODS: HeLa (HPV-18 positive),
      CaSki, and SiHa (both HPV-16 positive) contain wild-type p53, while C33A (HPV
      negative) expresses mutant p53. Fas cell surface expression was determined by
      flow cytometry. Expression of proteins involved in the apoptotic pathway was
      analyzed by Western blotting and apoptosis was measured by acridine orange
      staining of nuclear chromatin. RESULTS: Despite high Fas membrane expression in
      the HPV-positive cells, CaSki was highly sensitive, HeLa slightly sensitive, and
      SiHa and C33A were resistant for agonistic anti-Fas antibody. Almost undetectable
      Fas membrane levels can explain the non-responsiveness of C33A for anti-Fas.
      Although interferon-gamma (IFNgamma) strongly and cisplatin to a lesser extend
      enhanced Fas membrane expression in all HPV-positive cells, sensitization to anti
      Fas by IFNgamma or cisplatin was only observed in HeLa. Analysis of the Fas
      apoptotic pathway showed that anti-Fas treatment induced caspase-8 activation and
      concomitantly Bid cleavage, caspase-9 and caspase-3 activation, PARP cleavage and
      apoptosis in HeLa and CaSki. IFNgamma plus anti-Fas treatment, in contrast to
      anti-Fas alone, facilitated caspase-8 activation in HeLa and SiHa, while an
      increase in Bid cleavage, caspase-9 activation and apoptosis was only observed in
      HeLa. Apoptotic failure in SiHa (even in the presence of IFNgamma) was probably
      due to low caspase-8, almost undetectable Bid protein levels and therefore lack
      of caspase-9 activation. CONCLUSION: Sensitivity to anti-Fas depends on Fas,
      caspase-8, and Bid protein levels in cervical cancer cells. Additionally,
      IFNgamma and cisplatin can increase sensitivity to anti-Fas in a subset of HPV
      positive cervical cancer cell lines by upregulation of Fas and caspase-8
      expression without major changes in p53 levels.

PMID- 15863131
TI  - Down-regulation of peroxisome proliferator-activated receptor gamma in human
      cervical carcinoma.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a
      member of the nuclear hormone receptor superfamily. Treatment of PPARgamma
      ligands has been shown to inhibit the growth of various human cancer cells.
      However, it has not been reported whether human cervical carcinoma cells express
      PPARgamma. In this study, we investigated the expression of PPARgamma in human
      normal cervix and cervical carcinoma tissues, and as well as the effect of
      PPARgamma ligands on cervical cancer cells survival. METHODS: Fresh cervical
      tissues from a study group of 10 study patients diagnosed with cervical carcinoma
      were analyzed for the expression of PPARgamma using real-time RT-PCR and Western
      blot analysis. Immunohistochemical staining for PPARgamma was also performed on
      the serial sections of 40 cervical carcinomas. In addition, we evaluated the
      feasibility of PPARgamma ligands, as a potential therapeutic drug against
      cervical cancer cells using MTT assay and FACS analysis. RESULTS: We found that
      there were lower expression levels of PPARgamma mRNA and protein in cervical
      carcinoma tissues than in normal cervical tissues. The extent and intensity of
      immunoreactive PPARgamma in normal cervix tissues were statistically much greater
      than those of carcinoma tissues. In order to study effects of PPAR ligand on cell
      proliferation, we chose ciglitizone that showed very potent growth inhibitory
      effects on the proliferation of two human cervical cancer cell lines (C-33-A and
      C-4II). C-4II cells express high expression of PPARgamma, while C-33A cells
      express low level of PPARgamma. Treatment with ciglitizone inhibited the growth
      of C-4II cells in a dose-dependent manner, while the growth inhibitory effect of
      ciglitizone was much less in C-33A cells. In order to test whether ciglitizone
      induced growth suppressive effects on cervical cancer cell lines is PPAR
      dependent, we treated cervical cancer cells with ciglitizone and/or GW9662 (a
      PPARgamma antagonist). No significant difference in cell survival was found in
      cells treated with ciglitizone alone vs. co-treated with ciglitizone and GW9662.
      GW9662 alone did not induce any cell growth arrest in the cells that we used
      (data not shown). Thus, we concluded that growth suppressive effects by
      ciglitizone may not be dependent upon status of PPAR expression. To clarify the
      mechanism by which ciglitizone inhibits the growth of cervical carcinoma cells,
      flow cytometry and Western blotting assay were performed. As results, we
      demonstrated that a large portion of C-4II cells (but not in C-33A) after
      ciglitizone treatment were arrest at G1 phase with the induction of
      p21(Cip1/Waf1) and p27(kip1) protein. CONCLUSIONS: These results suggest that
      PPARgamma is down-regulated in multiple human cervical cancer tissues and cell
      lines. Ciglitizone may suppress human cervical cancer cells in PPAR-independent
      manner.

PMID- 15863132
TI  - Skin toxicity associated with pegylated liposomal doxorubicin (40 mg/m2) in the
      treatment of gynecologic cancers.
AB  - OBJECTIVES: To characterize the incidence of skin toxicity of pegylated liposomal
      doxorubicin (PLD) administered at a lower dose (40 mg/m(2)) in the treatment of
      advanced gynecologic malignancies. METHODS: Medical charts of all patients who
      initiated PLD at a starting dose of 40 mg/m(2) from 1997 to 2003 for the
      treatment of gynecologic cancers were retrospectively reviewed. PLD was infused
      over 1-2 h and administered every 4-6 weeks. No patient had previously received
      doxorubicin. All patients were clinically assessed for adverse reactions
      including skin toxicity. RESULTS: Ninety patients (mean age 62 years, range 45-82
      years) were included in this analysis. There were 55 ovarian, 16 endometrial, 2
      fallopian, and 17 primary peritoneal cancers. The median cumulative dose of PLD
      was 120 mg/m(2) (range 40-855 mg/m(2)) with a median of 3 cycles (range 1-25).
      33/90 (37%) developed a skin reaction during therapy. The overall incidence of
      grade 1, 2, and 3 skin toxicity was 23 (26%), 9 (10%), and 1 (1%), respectively.
      Of the 23 cases of grade 1 toxicity, 16 (70%) occurred within 1-3 cycles. All 9
      cases of grade 2 toxicity occurred within 1-3 cycles. The only case of grade 3
      toxicity occurred after the first cycle. 28/30 (93%) patients who continued
      treatment did not experience further episodes of skin toxicity with subsequent
      cycles after a dose reduction (5-20 mg/m(2)). PLD was stopped in only 2/90 (2%)
      cases due to a skin reaction. CONCLUSIONS: Severe skin toxicity (> or =grade 2)
      associated with PLD occurs infrequently when initial doses of 40 mg/m(2) are
      administered. When skin reactions appear, they usually occur early in the course
      of treatment, respond to dose reduction, and do not appear to limit the duration
      of treatment.

PMID- 15863133
TI  - Cytoplasmic CD24 expression in advanced ovarian serous borderline tumors.
AB  - OBJECTIVES: CD24, originally described as a B-cell marker, has been revealed as
      one of the candidate molecular markers of epithelial ovarian cancer. We aimed to
      determine the pattern and extent of CD24 expression in ovarian serous tumors and
      to clarify its relationship with pathological parameters, especially those
      associated with the early events of tumor progression in serous tumors of
      borderline malignancy. METHODS: A total of 114 ovarian serous tumors, including 9
      adenomas, 34 borderline, and 71 carcinomas, were analyzed immunohistochemically
      using a CD24 monoclonal antibody on paraffin blocks. RESULTS: In normal
      epithelium and serous cystadenomas, the CD24 expression was localized to the
      apical membranous portion. In some of borderline tumors (26.4%), additional
      cytoplasmic expression was observed. The cytoplasmic expression of CD24 in
      borderline tumors was associated with microinvasion (P = 0.001) and omental
      implants (P = 0.033) with statistical significance. Serous adenocarcinomas showed
      strong diffuse cytoplasmic expression of CD24, which was significantly associated
      with shortened survival rate both in univariate (P = 0.011) and multivariate (P =
      0.009) analysis. CONCLUSION: The loss of apical localization with the acquisition
      of the cytoplasmic staining of CD24 protein is a surrogate marker of stromal
      invasion in ovarian serous tumors of borderline malignancy. Furthermore, the
      increase in the cytoplasmic expression of CD24 protein is a strong independent
      molecular marker for shortened survival rate of patients with ovarian serous
      adenocarcinomas.

PMID- 15863134
TI  - Management strategies for stage IB2 cervical cancer: a cost-effectiveness
      analysis.
AB  - OBJECTIVE: To assess the potential effectiveness and medical costs of three
      common strategies to manage Stage IB2 squamous cell carcinoma of the cervix
      (CXCA). METHODS: A decision analysis model compared three strategies to manage
      Stage IB2 CXCA: (1) radical hysterectomy with pelvic and para-aortic
      lymphadenectomy followed by tailored chemoradiation therapy for high-risk
      patients (RHYST); (2) primary chemoradiation therapy for all patients (CTRT); and
      (3) neoadjuvant chemotherapy followed by radical hysterectomy and tailored
      chemoradiation therapy for high-risk patients (NAC). RESULTS: RHYST was the least
      expensive strategy with a cost of 284 Million (M) per 10,000 women and a 5-year
      disease free survival (5-DFS) of 69%. Both NAC and CTRT had similar 5-DFS (69.3%
      and 70%, respectively); however, both NAC and CTRT were more expensive than RHYST
      at 299 M and 508 M, respectively. This translated into a higher cost
      effectiveness ratio for NAC and CTRT ($43,197 and $72,613, respectively) when
      compared to RHYST ($41,212). NAC yielded 30 additional survivors compared to
      RHYST but at a cost of $499,783 per survivor. CTRT was more effective than RHYST
      with 100 additional survivors but at a substantial cost of $2,240,000 per
      survivor. CONCLUSIONS: RHYST is the most cost-effective strategy to manage Stage
      IB2 CXCA and would be favored in settings where resources are limited. Although
      NAC and CTRT are reasonable treatment strategies, policymakers must be willing to
      spend approximately $500,000 per additional survivor (NAC) or $2.2 M per
      additional survivor (CTRT).

PMID- 15863135
TI  - The accuracy of frozen section (intraoperative consultation) in the diagnosis of
      ovarian masses.
AB  - OBJECTIVE: Frozen section is an important and helpful adjunct in the
      intraoperative diagnosis of ovarian tumors. This retrospective study was
      undertaken to determine the accuracy of frozen section diagnosis of ovarian
      masses and the reasons of discordance. METHODS: From January 1995 to December
      2003, 1494 ovarian specimens were received for histopathological evaluation, and
      617 of them were submitted for frozen section examination. RESULTS.: The final
      paraffin section diagnoses of these 617 cases were a nonneoplastic lesion in
      18.3% of the cases, benign tumor in 56.1%, borderline tumor in 6.2%, and
      malignant tumor in 19.4%. The overall accuracy was 97%. Twenty-one cases were
      incorrectly diagnosed by frozen section. All of them were false negatives. There
      were no deferred cases. The majority of the cases of disagreement were mucinous
      and borderline tumors. The sensitivity for benign, borderline, and malignant
      tumors were 100%, 87%, and 87%, respectively. The specificity for benign tumors
      was 97%; for borderline tumors 98%; and for malignant tumors 100%. CONCLUSION:
      Our data confirm that frozen section diagnosis is a reliable method for the
      surgical management of patients with an ovarian mass. However, diagnostic
      problems can occur in mucinous and borderline tumors during frozen section
      examination. The clinicians and pathologists must be aware of the pitfalls of
      this method; therefore, a good communication established between them is
      necessary to obtain more accurate results and to minimize the number of deferred
      cases.

PMID- 15863136
TI  - Lymphatic metastasis in epithelial ovarian carcinoma with respect to
      clinicopathological variables.
AB  - OBJECTIVE: The purpose of this study was to evaluate the prognostic factors, and
      the patterns of lymphatic metastasis in EOC patients who were treated with
      systematic pelvic and paraaortic lymphatic dissection. METHODS: A total of 420
      EOC patients was retrospectively evaluated. Clinical factors available were
      evaluated for a possible significance in terms of lymphatic metastasis and
      paraaortic involvement. RESULTS: Two-hundred and three patients were found to
      have lymphatic metastasis. In multivariable analysis, stage (P < 0.001),
      histology (P < 0.01 for serous; P = 0.02 for mixed, and P = 0.04, for Brenner),
      and Ca-125 level higher than 500 U/ml (P = 0.04) were found to be significantly
      related with the lymphatic involvement. Age and grade were significant factors
      for paraaortic metastasis both in univariable and multivariable analysis (P =
      0.003 and P = 0.02, respectively). Most of the patients with unilateral tumors
      had contralateral pelvic and/or paraaortic metastasis. There were eleven patients
      with lymphatic metastasis in stage I-II disease, and five had paraaortic
      metastasis while an additional five patients had contralateral pelvic nodal
      metastasis. However, there was no lymphatic involvement in Stage IA, Grade I-II
      disease (0/63). Survival analysis revealed no significant difference by the
      number of metastatic lymph nodes. CONCLUSION: In multivariable analysis,
      lymphatic involvement was predicted independently by stage, histology, and Ca-125
      level. In apparently stage I-II disease, a considerable part of patients were
      upstaged due to lymphatic involvement. Although routine systematic
      lymphadenectomy is suggested for patients with early stage disease, further
      series are needed for a definite regimen in patients with stage IA G1-2 disease
      since we did not detect any lymphatic involvement in this unique group.

PMID- 15863137
TI  - Inhibitory effects of herbal drugs on the growth of human ovarian cancer cell
      lines through the induction of apoptosis.
AB  - OBJECTIVE: In order to develop and search for more effective and safe treatments
      for early and advanced stages of ovarian cancer, we examined the direct effects
      of four extracts of Chinese herbal drugs on ovarian cancer cells in vitro.
      METHODS: The growth inhibition of four herbal drugs on a total of six cell lines
      of human ovarian cancer cells was determined by a Cell Counting Kit-8 by counting
      viable cells. Apoptotic cells induced by herbal drugs were detected by using
      MEBCYTO Apoptosis Kit. All experiments were performed in triplicate. The
      significance of the difference was analyzed with a two-sided Student's t test. A
      P value less than 0.05 was accepted as statistically significant. RESULTS: The
      MN, A2780, and KF cell lines exhibited significant growth inhibition in the
      presence of Sho-saiko-to concentrations of 150 microg/ml, 300 microg/ml, and 500
      microg/ml, respectively, and at the concentration of 1000 microg/ml, Sho-saiko-to
      demonstrated a significant apoptotic induction effect on all six kinds of ovarian
      cancer cell lines. This concentration is the same as the blood concentration
      attained when 7.5 g of Sho-saiko-to per day is orally administered and all
      absorbed. CONCLUSIONS: Sho-saiko-to exhibited significant growth inhibition of
      ovarian cancer cell lines, and the mechanisms of the inhibitory effects can be
      attributed, in part, to apoptosis induced by Sho-saiko-to.

PMID- 15863138
TI  - Chemotherapy-induced changes of CA 125 in patients with epithelial ovarian
      cancer.
AB  - OBJECTIVES: CA 125 is a tumor marker widely used to diagnose, monitor, and follow
      up women with epithelial ovarian cancer, as the marker is well related to the
      amount of vital tumor cells. However, CA 125 before the operation or during the
      first 2 courses of chemotherapy does not provide enough information concerning
      survival to serve as a prognostic marker. The present investigation was inspired
      by studies describing a paradoxical increase of tumor markers (CEA, CA 125, and
      CA 15-3) in the days after chemotherapy of women with breast cancer. If CA 125
      increases within days after chemotherapy, the increase may be caused by death of
      the cancer cells. It was therefore speculated if a CA 125 spike may serve as an
      early prognostic parameter. The aim of the present investigation was to evaluate
      if CA 125 increases within days after the first course of chemotherapy of women
      with ovarian cancer. PATIENTS: Twenty women with epithelial ovarian cancer were
      included in the study. CA 125 was measured in each woman on day 0 (the day of,
      but before initiation of chemotherapy) and 1, 3, 5, 7, 9, and 14 days after
      chemotherapy. RESULTS: One woman was excluded due to normal CA 125 values. The
      remaining 19 patients displayed a significant decrease in CA 125 during the 14
      day period after chemotherapy. CONCLUSION: In the present study, no chemotherapy
      induced increase of CA 125 within the first 14 days after chemotherapy could be
      demonstrated.

PMID- 15863139
TI  - Regulation of HtrA2/Omi by X-linked inhibitor of apoptosis protein in
      chemoresistance in human ovarian cancer cells.
AB  - OBJECTIVE: Development of cisplatin resistance by cancer cells is a major hurdle
      in successful treatment of human ovarian cancer. However, the mechanism of
      cisplatin resistance in ovarian cancer cells remains unclear. In this study, we
      have examined the possible role of X-linked inhibitor of apoptosis protein (Xiap)
      in the development of cisplatin resistance in ovarian cancer cells and
      investigate if suppressed cytosolic high temperature required protein A
      (HtrA2/Omi) level is an important factor in cisplatin resistance in ovarian
      cancer. METHODS: Cisplatin-sensitive (A2780 and COC1) and -resistant (A2780/DDP
      and COC1/DDP) ovarian cancer cells were cultured for different durations (0-24 h)
      and with different cisplatin concentrations (0-20 muM). Xiap content and
      cytosolic HtrA2/Omi content were analyzed by Western blot. Antisense
      oligonucleotides were used to downregulate Xiap content in ovarian cancer cells.
      RESULTS: Cisplatin decreased Xiap content and increased cytosolic HtrA2/Omi
      content and caspase-3 activity in cisplatin-sensitive ovarian cancer cell lines
      (A2780 and COC1), but not in the resistant variants (A2780/DDP and COC1/DDP).
      Downregulation of Xiap by antisense Xiap oligonucleotides increased caspase-3
      activity and sensitized cisplatin-resistant cells to cisplatin treatment.
      Cytosolic HtrA2/Omi level increased while Xiap was downregulated in cisplatin
      resistant ovarian cancer cells. CONCLUSION: Development of cisplatin resistance
      may be due to Xiap neutralizing caspase-3 activation and lower cytosolic
      HtrA2/Omi level in response to cisplatin in human ovarian cancer cells. Cytosolic
      HtrA2/Omi level is partly regulated by Xiap in ovarian cancer cells.

PMID- 15863140
TI  - Associations among exercise, body weight, and quality of life in a population
      based sample of endometrial cancer survivors.
AB  - OBJECTIVES: Lack of exercise and excess body weight may exacerbate treatment
      related declines in quality of life (QoL) in endometrial cancer survivors. The
      primary purpose of this study was to examine the associations among exercise,
      body weight, and QoL in a population-based sample of endometrial cancer
      survivors. METHODS: Participants were 386 endometrial cancer survivors residing
      in Alberta, Canada who completed a mailed survey that assessed self-reported
      exercise, height, and weight to calculate body mass index (BMI) and QoL using the
      Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale. RESULTS:
      Descriptive data indicated that 70% of the sample were not meeting public health
      exercise guidelines and 72% were overweight or obese. Multivariate analyses of
      variance demonstrated that endometrial cancer survivors meeting public health
      guidelines for exercise and body weight reported significantly better QoL than
      survivors not meeting guidelines. The differences in QoL between the groups were
      clinically meaningful and were not altered when controlling for important
      demographic and medical variables. There were no interactions between exercise,
      BMI, age, or time since diagnosis. Lastly, multiple regression analysis
      identified that both exercise (beta = .21; P < .001) and BMI (beta = -.17; P <
      .001) were independently associated with QoL. CONCLUSIONS: These results suggest
      that exercise and body weight are important independent correlates of QoL in
      endometrial cancer survivors. Randomized controlled trials designed to test the
      causal effects of exercise and/or weight loss on QoL in endometrial cancer
      survivors are warranted.

PMID- 15863141
TI  - Cyclin D1 polymorphism and the risk of endometrial cancer.
AB  - OBJECTIVES: The common G to A single nucleotide polymorphism (G870A) in the
      splice donor region of exon 4 enhances alternate splicing, and produces a longer
      half-life cyclin D1 (CCND1). This study was aimed at investigating the possible
      association between the G870A polymorphism in CCND1 and the risk of endometrial
      cancer. METHODS: We assessed the association between the CCND1 G870A polymorphism
      and the risk of endometrial cancer in a hospital-based case-control study among
      231 Korean women (77 cases; 154 matched controls). Controls were matched to cases
      with respect to age, menopausal status, and hormone therapy status. RESULT: The
      allele frequencies of the case subjects (A, 0.45; G, 0.55) were significantly
      different from those of control subjects (A, 0.58; G, 0.42) (P = 0.008). All case
      and control subjects were in Hardy-Weinberg equilibrium. The AA genotype was
      associated with a significantly elevated odds ratio (OR) of 3.18 [95% confidence
      interval (CI) 1.38-7.37, P = 0.007], and the AG genotype was associated with an
      OR of 1.38 (95% CI 0.65-2.89). When we combined the GG and AG genotypes as a
      reference genotype, we found that the OR for the AA genotype was 2.53 (95% CI
      1.34-4.80, P = 0.004), supporting a recessive model for the A allele. Conditional
      logistic regression adjusted for various risk factors of endometrial cancer
      revealed positive associations between the AA genotype and an increased risk of
      endometrial cancer (OR 3.16, 95% CI 1.18-8.43, P = 0.022). However, no
      significant difference in endometrial cancer stage or grade was observed between
      the CCND1 genotypes. CONCLUSION: Our data suggest that the CCND1 polymorphism is
      associated with an increased risk of endometrial cancer. To validate this
      association, a large-scale population-based study is needed.

PMID- 15863142
TI  - Advanced stage mucinous epithelial ovarian cancer: the Hellenic Cooperative
      Oncology Group experience.
AB  - OBJECTIVE: Mucinous epithelial ovarian cancer (mEOC) representing about 10% of
      all EOC are known to be possibly resistant to platinum-based chemotherapy and
      bear a poorer prognosis with respect to other subtypes of EOC. This study was
      undertaken to compare response and survival to platinum-based chemotherapy
      between patients with advanced stages III and IV mEOC and serous EOC (sEOC).
      METHODS: A retrospective analysis was performed in 47 patients with advanced
      stage of mEOC treated with first-line platinum-based chemotherapy in the context
      of several study protocols of the Hellenic Cooperative Oncology Group (HeCOG)
      between 6/7/1983 and 25/2/2003. The outcome was compared to that of 94 patients
      with sEOC treated with the same protocols during the same study period (ratio
      mucinous: serous 1:2). RESULTS: One hundred forty-one patients (47 stages III and
      IV mEOC, 94 stages III and IV sEOC) treated with platinum-based chemotherapy were
      analyzed. The overall response rate for mEOC was 38.5% (complete remission 18%)
      (95% CI 23.4-55.4%) and 70% (complete remission 47%) (95% CI 58.5-80.3%) for sEOC
      (P = 0.001). After a median follow-up of 77.8 months, median survival and time to
      tumor progression (TTP) were not significantly different between the two groups
      (33.2 months [95% CI 23.3-43.1 months] vs. 38.0 months [95% CI 26.8-49.2 months],
      P = 0.46, 11.8 months [95% CI 7.2-16.4 months] vs. 20.0 months [95% CI 15.7-24.2
      months], P = 0.18, respectively). CONCLUSION: Patients with mEOC have
      significantly lower response to first-line platinum-based chemotherapy compared
      to patients with sEOC. This low response to platinum-based chemotherapy was not
      translated in inferior TTP or survival. Our data indicate that a new strategy for
      chemotherapy in mEOC should be adopted, one that focuses on new agents without
      cross-resistance to platinum agents.

PMID- 15863143
TI  - Malignant mixed mullerian tumor (MMMT) of the cervix.
AB  - OBJECTIVES: To characterize the clinical characteristics, therapeutic options,
      and potential outcomes in patients diagnosed with malignant mixed mullerian tumor
      (MMMT) of the uterine cervix. METHODS: Five women ranging in age from 25 to 66
      (mean 49.6 years) were diagnosed with MMMT of the cervix and treated at the
      University of Iowa Hospitals and Clinics between 1986 and 2001. Data were
      retrospectively analyzed from available charts and pathological reports with
      particular attention to patient demographics, presenting symptoms, treatment, and
      follow-up. RESULTS: Abnormal vaginal bleeding was a common presenting symptom in
      all but one patient, in whom an abnormal screening Pap smear was the primary
      reason for referral. FIGO disease staging at initial diagnosis included two
      patients with stage IB1 (ages 29 and 66 years), two patients with stage IB2 (ages
      25 and 64 years), and one patient with stage IVB (age 64 years) MMMT of the
      cervix. Organ-confined, early stage lesions (stages IB1 and IB2) responded well
      to regimens of either surgery alone or surgery plus radiation therapy, with no
      evidence of recurrent disease at last follow-up 28, 35, 42, and 65 months later,
      respectively. The lone patient with advanced stage IVB disease, however, was
      unresponsive to both external beam radiation therapy and ifosfamide chemotherapy,
      and succumbed to disease within 5 months. CONCLUSIONS: Cervical MMMT is an
      uncommon disease, but long-term survival is possible in organ-confined early
      stage disease with primary therapy.

PMID- 15863144
TI  - Development of ovarian cancer surgery quality indicators using a modified Delphi
      approach.
AB  - OBJECTIVE: Little performance measurement has been undertaken in the area of
      oncology, particularly for surgery which is a pivotal event in the continuum of
      cancer care. This work was conducted to develop indicators of quality ovarian
      cancer surgery using a modified three-step Delphi approach. METHODS: A
      multidisciplinary panel, comprised of surgical and methodologic co-chairs, nine
      surgeons, one medical oncologist, one radiation oncologist, a nurse, and a
      pathologist, reviewed potential indicators extracted from the medical literature
      through two consecutive rounds of rating followed by consensus discussion. The
      panel then prioritized the indicators selected in the previous two rounds.
      RESULTS: Of 33 possible indicators that emerged from 41 selected articles, 14
      were prioritized by the panel as benchmarks for assessing the quality of surgical
      care. The 14 indicators represent three levels of measurement
      (provincial/regional, hospital, individual provider) across several phases of
      care (diagnosis, surgery, pathology, and adjuvant therapy), as well as broad
      measures of access and outcomes. Some of the indicators selected by the panel
      were also recommended as standards of care by national initiatives in other
      countries. CONCLUSIONS: A systematic evidence- and consensus-based approach was
      used to develop quality indicators of ovarian cancer care, with a focus on pre-,
      peri-, and postoperative care as well as outcomes, that are applicable in any
      jurisdiction.

PMID- 15863145
TI  - Intra-abdominal carcinomatosis after prophylactic oophorectomy in women of
      hereditary breast ovarian cancer syndrome kindreds associated with BRCA1 and
      BRCA2 mutations.
AB  - OBJECTIVE: Prophylactic surgical removal of the ovaries has been offered for many
      years as a potential preventative of ovarian cancer in women deemed to be at
      increased hereditary risk for this disease. Now, it is possible to test for
      specific mutations of the BRCA1 and BRCA2 genes that render members of hereditary
      breast ovarian cancer (HBOC) syndrome families susceptible to cancer. Widespread
      intra-abdominal carcinomatosis, which mimics metastatic ovarian serous carcinoma,
      has been reported following oophorectomy in individuals at increased hereditary
      risk. This study was undertaken to examine and report particularly the occurrence
      of intra-abdominal carcinomatosis, as well as other cancers, following
      prophylactic oophorectomy in patients who carry cancer susceptibility mutations
      of BRCA1 and BRCA2 and to assess the cumulative risks for this disease in order
      to assist in developing appropriate surgical interventions, based on currently
      available information, and to counsel patients who choose prophylactic surgery,
      concerning the potential prognosis, thereafter. METHODS: The Creighton University
      Hereditary Cancer Institute registry was searched for members of HBOC syndrome
      families who had undergone prophylactic oophorectomy. The histories and results
      of DNA testing for the BRCA1 and BRCA2 mutations carried in their families were
      recorded, tabulated and examined, and the aggregate data are reported along with
      pertinent details of those individuals who developed neoplastic diseases after
      prophylactic oophorectomy. All available histologic and cytologic materials of
      patients who were diagnosed with intra-abdominal carcinomatosis were reviewed,
      and life-table calculations were performed to assess cumulative risks for this
      disease following prophylactic oophorectomy. RESULTS: From 72 HBOC syndrome
      families that carried either BRCA1 or BRCA2 cancer-associated mutations, 238
      individuals who had undergone prophylactic oophorectomy were recorded in our
      registry between January 1985 and December 2002. During a mean follow-up of 9.3
      years, cancers were diagnosed in 27 subjects, including 16 individuals with
      breast cancer and five patients with intra-abdominal carcinomatosis. Breast
      cancers were stage I in 10 of 12 proven carriers of cancer-associated mutations.
      All five cases of intra-abdominal carcinomatosis were serous carcinomas, and all
      occurred in BRCA1 mutation carriers. Histologic review of the prophylactically
      removed ovaries found borderline lesions in two cases, one with possible early
      stromal invasion. Two of the five patients who developed intra-abdominal
      carcinomatosis were among 78 patients in this series who were diagnosed and
      treated for breast cancer before prophylactic oophorectomy. A 3.5% cumulative
      risk for all mutation carriers and a 3.9% cumulative risk for BRCA1 mutation
      carriers were calculated through 20 years of follow-up after prophylactic
      oophorectomy. CONCLUSIONS: Intra-abdominal carcinomatosis in our series was
      diagnosed only in BRCA1 mutation carriers. The calculated cumulative risks of
      developing intra-abdominal carcinomatosis after prophylactic oophorectomy in
      members of HBOC syndrome families, specifically those who carry deleterious
      mutations, are well below the estimated risks of ovarian cancer published in the
      literature for similar patients. Breast cancers, which tended to be small and
      localized, were the most common malignancy in BRCA1 and BRCA2 mutation carriers
      after prophylactic oophorectomy.

PMID- 15863146
TI  - Pretreatment laparoscopic surgical staging in locally advanced cervical cancer:
      preliminary results in Korea.
AB  - OBJECTIVES: The purpose of this study was to evaluate the feasibility and
      efficacy of pretreatment laparoscopic surgical staging in the treatment of
      locally advanced cervical cancer. METHODS: Forty-four patients with locally
      advanced cervical cancer who underwent pretreatment laparoscopic surgical staging
      between October 2001 and April 2004 were reviewed. The pathological diagnosis
      after laparoscopic surgical staging was compared with results from preoperative
      magnetic resonance imaging (MRI), and surgical results with follow-up data were
      evaluated. RESULTS: The mean duration of surgery was 202.0 (range: 120-300) min
      and the mean number of harvested lymph nodes (LNs) was 38.7 (range: 20-75).
      Twenty (45.5%) patients had pelvic LN metastasis and 5 (11.4%) patients had
      pelvic and para-aortic LN metastasis. Region-specific findings of MRI resulted in
      sensitivity and positive predictive values of 55.9% and 48.7%, respectively, on a
      three-region analysis. When compared with MRI, laparoscopic surgical staging was
      superior in detecting microscopic LN metastasis. The time to commencing
      concurrent chemoradiotherapy after laparoscopic surgical staging was 8.6 +/- 3.3
      (mean +/- SD) days. All the patients received concurrent chemoradiotherapy as
      scheduled. There were three (6.8%) cases of minor postoperative complications,
      and no mortality occurred during the follow-up period. The 2-year disease-free
      survival rate of the current study was 89.7%, and three (6.8%) patients
      experienced recurrence after treatment. CONCLUSIONS: Laparoscopic surgical
      staging in locally advanced cervical cancer is a feasible and safe pretreatment
      method, and can be used as a best guideline for individualized concurrent
      chemoradiotherapy.

PMID- 15863147
TI  - Outcome of surveillance and prophylactic salpingo-oophorectomy in asymptomatic
      women at high risk for ovarian cancer.
AB  - OBJECTIVE: Women at high risk of ovarian cancer are currently offered two
      options: either surveillance or prophylactic bilateral salpingo-oophorectomy. The
      efficacy and outcome of surveillance remain unclear. METHODS: We performed a
      retrospective study. Between 1994 and 2000, we screened 383 high-risk women, of
      which 152 were BRCA1/2 mutation carriers. Surveillance consisted of annual
      gynecological examination, transvaginal ultrasound, and serum CA125 measurement.
      Exploratory or prophylactic surgery was performed in selected cases. RESULTS:
      There were no screen-detected primary ovarian cancers. Abnormal results at
      surveillance were observed in 74 (19.3%) of women; in 47 (63.5%), the
      abnormalities disappeared spontaneously. Exploratory surgery was performed in 20
      (27.0%) women in whom one malignancy was found (metastatic breast cancer in the
      ovary). A rising CA125 value prompted further (non-surgical) evaluation in three
      women with a history of breast cancer: recurrent breast cancer was diagnosed in
      two women; in the third, a chondrosarcoma was found. 133 women opted for
      prophylactic bilateral salpingo-oophorectomy, whereby two unexpected malignancies
      were found (fallopian tube cancer and metastatic breast cancer). One interval
      primary ovarian cancer occurred, presenting as papillary serous carcinoma of the
      peritoneum 14 months after prophylactic bilateral salpingo-oophorectomy.
      Complications of prophylactic surgery were encountered in 15 (11.5%) women.
      CONCLUSIONS: Ovarian cancer surveillance has limited sensitivity, and a high
      number of false positive findings. This can lead to unnecessary surgical
      interventions, possibly resulting in surgery-related complications. It is
      important to inform high-risk women of these limitations. For now, prophylactic
      bilateral salpingo-oophorectomy remains the optimal risk-reducing strategy for
      women at high risk.

PMID- 15863148
TI  - Estrogen and progesterone receptors and cyclooxygenase-2 expression in
      endometrial cancer, endometrial hyperplasia, and normal endometrium.
AB  - OBJECTIVES: To determine whether cyclooxygenase-2 (COX-2) expression is seen in
      endometrial cancer, endometrial hyperplasia, and normal endometria and whether it
      correlates with expression of estrogen and progesterone receptors. METHODS: The
      study was a retrospective, IRB-approved analysis of biopsy samples from 14
      patients with endometrial adenocarcinoma, 19 with endometrial hyperplasias, and
      10 with normal endometrium. Excluded were samples from women with a history of
      pelvic radiation, NSAID use, or treatment with hormones during previous year.
      Immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded
      tissues. Expression of COX-2, estrogen and progesterone receptors were scored
      according to the proportion of positive-staining cells: 1(+), <10%; 2(+), 10-50%;
      and 3(+), >50%. A score > or =2(+) was considered positive. Fisher's exact test
      and analysis of variance were used to compare proportions and continuous
      variables, respectively. RESULTS: Overexpression of COX-2 was seen in 4 (29%) of
      the endometrial cancers, 6 (32%) of the endometrial hyperplasia, and 4 (20%) of
      the normal endometria. These differences were not statistically significant (P =
      0.90). No COX-2 expression was found in stromal tissue. Of 14 endometrial
      cancers, 7 (50%) expressed any COX-2, with 4 (29%) having an expression score of
      > or =2(+). Of 19 endometrial hyperplasias, 11 (58%) expressed any COX-2; with 6
      (32%) having a score of > or =2(+). All 10 normal endometria showed only 1(+)
      expression. No significant differences were detected in COX-2 expression by grade
      or stage of cancer. Although 100% and 95% of both hyperplasia and normal
      endometrium samples expressed in estrogen and progesterone receptors,
      respectively, only 71% and 79% of endometrial cancers expressed estrogen and
      progesterone receptors (P = 0.01). A nonparametric trend was performed to detect
      a relationship, between COX-2 and estrogen receptor or progesterone receptor
      expression; no significant trend was found. CONCLUSIONS: In this study, the
      immunohistochemical analysis showed a trend toward increased COX-2 expression in
      endometrial cancer and hyperplasia compared to normal endometria. A larger sample
      size is needed to confirm these results. The increased COX-2 expression in
      hyperplasia may signify an early step in carcinogenesis. These findings may
      represent an important treatment opportunity for synergism in the hormonal
      therapy of endometrial cancer.

PMID- 15863149
TI  - The activity of taxanes compared with bleomycin, etoposide, and cisplatin in the
      treatment of sex cord-stromal ovarian tumors.
AB  - OBJECTIVE: We compared the efficacy and side effects of taxanes, with or without
      platinum, to bleomycin, etoposide, and cisplatin (BEP) in treating sex cord
      stromal ovarian tumors. METHODS: We conducted a retrospective review of all
      patients with sex cord-stromal ovarian tumors seen at our institution from 1985
      to 2002. Eligible patients were those who underwent pathologic confirmation,
      clinical evaluation, and treatment with a taxane or BEP for initial or recurrent
      disease. RESULTS: Of 222 patients identified, 21 received BEP for new (n = 11) or
      recurrent disease (n = 10); 44 received a taxane during 48 treatment episodes
      (four patients on two occasions each) for new (n = 11) or recurrent disease (n =
      37). Newly diagnosed patients treated with BEP vs. taxanes had no significant
      difference in response rate (Fisher's exact test, P = 1), progression-free
      survival (PFS) (log-rank test, P = 0.213), or overall survival (log-rank test, P
      = 0.994). Among patients treated for recurrent measurable disease, the response
      rate was higher for BEP-treated (71%) than for taxane-treated patients (37%), but
      this was not statistically significant. In all patients treated for recurrent
      disease, there was no significant difference in failure to progress at
      chemotherapy completion between BEP- (70%) and taxane-treated patients (62%) or
      in median PFS (11.2 vs. 7.2 months). The presence of platinum in taxane
      containing regimens correlated with response. Taxane-related side effects
      included neutropenia (n = 6), anemia (n = 1), thrombocytopenia (n = 1),
      myelodysplasia (n = 1), and hypersensitivity (n = 1). BEP-related side effects
      included pulmonary fibrosis (n = 3) and neutropenia (n = 2). CONCLUSIONS: Taxanes
      demonstrated activity against sex cord-stromal tumors of the ovary and may be
      less toxic than BEP. Taxane and platinum combination chemotherapy warrants
      further investigation in this disease.

PMID- 15863150
TI  - DCS liquid-based system is more effective than conventional smears to diagnosis
      of cervical lesions: study in high-risk population with biopsy-based
      confirmation.
AB  - OBJECTIVE: To compare the performances of Papanicolaou test (PapTest) and of a
      new liquid-based cytology method, DNA-Citoliq System (DCS), in a high-risk
      population, with histology confirmation. METHODS: Paired specimens of exfoliated
      cervical cells were collected under split-sample protocol. All patients were
      submitted to colposcopy and a biopsy taken when any atypical transformation zone
      was seen. Sensitivity, specificity, positive and negative predictive values, and
      overall accuracy of both conventional and DCS methods were computed in relation
      to histology. RESULTS: A total of 1095 patients were analyzed by two cytology
      methods and, in 425 (38.8%), histologically. There were significantly more
      adequate samples with DCS (98.63%) than with conventional (89.6%) smears (P <
      0.001). ASCUS was diagnosed significantly more with DCS than with conventional
      Pap (P < 0.001). Conventional Pap misclassified as normal 55.4% (158/285) of
      cases with either LSIL or HSIL or cancer at histology, whereas DCS misclassified
      31.2% (89/285) of cases (P < 0.001). DCS had a significantly higher sensitivity
      (70% and 91.3%) than the conventional Pap (49.8% and 72.8%) to detect both LSIL+
      and HSIL+ at histology, respectively. On the other hand, specificity of
      conventional smear (88.2% and 85.2%) was significantly higher than DCS (75.4% and
      70.9%) considering both LSIL+ and HSIL+ at histology, respectively. CONCLUSIONS:
      This study confirms the superiority of the liquid-based cytology system DCS to
      detect cervical lesions. The rate of adequate DSC slides was significantly higher
      than with conventional cytology.

PMID- 15863151
TI  - Reversal of multidrug resistance by small interfering double-stranded RNAs in
      ovarian cancer cells.
AB  - OBJECTIVE: Cisplatin (DDP) resistance is a major barrier to overcome before
      chemotherapy can become curative for most patients presenting with ovarian
      cancer. In this study, we investigated the effect of siRNAs on expression of p
      gp, GST-pi mRNA and protein in cisplatin-resistant human ovarian cancer cells in
      order to restore sensitivity to DDP. METHODS: Small interfering double-stranded
      RNAs (siRNA) were designed to target p-glycoprotein (p-gp) and glutathione S
      transferases (GST) mRNA as a strategy to inhibit both resistant gene expression
      at the mRNA level. Using Real-Time PCR and western blotting assay the changes of
      the RNA and protein levels of both drug resistant genes were studied. RESULTS:
      Transfection of MDR-1 and GST siRNAs into human multi-drug resistance (MDR)
      ovarian cancer cell lines, COC1/DDP and SKOV3/DDP, resulted in a time-dependent
      inhibition of both gene expressions with the decline of the IC(50) values but had
      no effect on the expression of a-Tubulin. Inhibition of P-gp and GST expression
      by siRNA enhanced the intracellular accumulation of and restored sensitivity to
      DDP. CONCLUSIONS: These studies suggest that p-gp and GST siRNAs are effective
      inhibitors of MDR gene expression and reverse the resistance of ovarian
      carcinomas. Our studies may provide a new insight to develop siRNAs as a novel
      therapeutic tool for the treatment of ovarian carcinomas.

PMID- 15863152
TI  - Long-term results of high-dose rate brachytherapy in cervix cancer using a small
      number of fractions.
AB  - OBJECTIVES: To evaluate the long-term treatment outcome of patients with
      carcinoma of the cervix treated with high dose rate brachytherapy (HDRB) using a
      small number of fractions. METHODS: Between 1984 and 1997, 282 patients with
      cervix cancer (stages IB to IVA) were treated with external beam radiotherapy to
      the whole pelvis (median dose of 45 Gy) and HDRB (median dose of 24 Gy at point A
      in 3 insertions given weekly). Endpoints assessed were survival, patterns of
      failure and complications. Multivariate analysis was performed to identify
      variables predictive for overall survival and local control. Variables
      investigated were stage, age, overall duration of treatment, HDRB scheduling and
      total dose to point A. RESULTS: At a median follow-up of 86.3 months for patients
      at risk, the 5-, 10- and 15-year overall survival rates are 57%, 52% and 47%,
      respectively. On multivariate analysis, only stage and age correlated with
      improved survival. Treatment duration beyond 47 days was associated with poorer
      overall survival, although it did not reach statistical significance (P = 0.10).
      Brachytherapy scheduling and BED to point A had no impact on overall survival.
      Stage and age significantly correlated with pelvic disease control. Duration of
      therapy, scheduling of the brachytherapy and BED at point A were not individual
      predictors for overall local control. Overall, gastrointestinal and genitourinary
      actuarial complication rates were 15% and 8%, respectively. CONCLUSIONS: In our
      experience, HDRB using 3 insertions is well tolerated and the results are
      comparable to HDRB using larger number of fractions and to low dose rate
      brachytherapy.

PMID- 15863153
TI  - Common death receptor 4 (DR4) polymorphisms do not predispose to ovarian cancer.
AB  - OBJECTIVE: Polymorphisms of death receptor 4 (DR4) might impair the apoptotic
      signal transduction and lead to dysregulation of the homeostasis between cell
      survival and cell death, promoting tumor development and progression. METHODS: We
      performed an analysis of known DR4 polymorphisms, namely G442A, C626G, and
      A1322G, in germ line DNA of 97 ovarian cancer patients and controls as well as in
      established ovarian cancer cell lines. RESULTS: Patient and matched control
      populations were not differing significantly in case of G442A (P = 0.736) and
      C626G alterations (P = 0.699). For the A1322G transversion, we generated
      population data for the first time and could find a rate of 19% heterozygotes and
      3% homozygotes. Again, we could not detect any significant difference between
      patients and controls (P = 0.326). CONCLUSION: To summarize, alterations of the
      DR4 gene do not lead to clinically relevant ovarian cancer predisposition and are
      therefore most unlikely to contribute to familial ovarian cancer.

PMID- 15863154
TI  - Ovarian cancer incidence in the United States, 1992-1999.
AB  - OBJECTIVE: The purpose of this epidemiological study was to report histology
      specific age-adjusted ovarian cancer incidence rates that were standardized to
      the recently adopted year 2000 United States standard population. METHODS: We
      utilized data gathered from eleven population-based cancer registries of the
      Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer
      Institute for the years 1992 through 1999. Our analyses included data on 23,484
      microscopically confirmed cases of primary malignant ovarian cancer that were
      diagnosed in women residing in the eleven SEER registries. RESULTS: We
      categorized the 117 different histologies that were diagnosed in the 23,484
      ovarian cancer cases into ten major classifications. The overall age-adjusted
      incidence rate for all ovarian cancer cases was 16.23 cases per 100,000 women.
      Epithelial tumors displayed the highest age-adjusted incidence rate (15.48),
      followed by germ cell tumors (0.41), sex cord-stromal tumors (0.20), and all
      other miscellaneous ovarian tumors (0.13). Serous epithelial tumors were the most
      commonly observed epithelial group (6.77 cases per 100,000 women), followed by
      other miscellaneous epithelial tumors (3.76), mucinous epithelial tumors (2.22),
      endometrioid epithelial tumors (2.11), and clear cell epithelial tumors (0.64).
      Notable differences were observed in the age-adjusted incidence rates for White
      and Black women. CONCLUSIONS: Age-adjusted incidence rates of ovarian cancer vary
      by histology. This is the first study to standardize histology-specific age
      adjusted incidence rates of ovarian cancer to the new 2000 United States standard
      population.

PMID- 15863155
TI  - Long-term follow-up of continent urinary diversion after pelvic exenteration for
      gynecologic malignancies.
AB  - OBJECTIVE: The objective of this retrospective study was to analyze the long-term
      outcome of patients undergoing a continent urinary diversion (UD) at the time of
      pelvic exenteration (PE). PATIENTS AND METHODS: Between February 1993 and January
      2001, 60 PE for gynecologic malignancies and requiring a UD were performed.
      Patient's preference, type of UD planned, type of UD performed, and late urinary
      morbidity (after day 90) were analyzed. RESULTS: Eighty-two percent of the entire
      group (49/60) matched preoperatively criteria to have a continent UD and 41
      continent UD were eventually performed (87%). Postoperative mortality in patients
      with a continent UD was 4.9% (2/41) and wasn't related to urinary complications.
      After a 20-month median follow-up, 18 patients (46%) with a continent UD
      developed late complications directly UD-related. These complications were: (a)
      major in 28% (5/18) requiring re-operation in 3 cases or endoscopic treatment in
      2 cases; (b) minor in 72% (13/18) constantly medically treated. Chronic diarrhea
      was more frequent in patient who had small bowel or left colon resection (P <
      0.05) and urine leakage was more frequent in patient with higher BMI (P < 0.05).
      At last follow-up, no patient had stopped self-catheterizations or asked for
      undiversion. CONCLUSIONS: In our experience, continent UD at the time of PE
      despite high acceptability and feasibility rate, appeared to be strongly related
      to specific late complications, uncommon with ileal conduit. However, these
      complications remained more frequently minor and could be treated safely and
      conservatively.

PMID- 15863156
TI  - CA-125 AUC as a new prognostic factor for patients with ovarian cancer.
AB  - OBJECTIVE: The aim of the present study was to investigate the usefulness of the
      CA-125 area under the curve (AUC) as a new kinetic parameter for predicting
      overall survival in patients with ovarian cancer. In addition, the relationship
      of CA-125 AUC with other prognostic factors of ovarian cancer was evaluated.
      METHODS: Ninety-two patients that underwent primary line chemotherapy within 4
      months after submission to cytoreductive surgery were included. For each patient,
      CA-125 AUC was calculated and a statistical analysis was conducted to compare CA
      125 AUC behavior among patients according to several covariates. RESULTS: The
      mean age at diagnostic time was found to be 55.5 (16.1-82.4) years with a mean
      survival of 39.2 (3.5-100.1; SE = 2.6) months. Across FIGO stage I, II, III, and
      IV patients had a mean CA-125 AUC of 18.2, 24.6, 147.8, and 574.6 IU/ml*days,
      respectively (P < 0.05). At the evaluation date, living patients had a mean CA
      125 AUC of 40.1 in contrast to 234.1 IU/ml*days (P < 0.05) for deceased ones.
      Patients with a complete response to primary chemotherapy had a mean CA-125 AUC
      of 48.8, while patients with a partial response had a mean of 251.7 IU/ml*days,
      and patients with no response or disease progression had a mean of 316.5
      IU/ml*days (P < 0.05). The best CA-125 AUC performance is in predicting patient
      complete response to chemotherapy with a cut-off of 100 IU/ml*days and an
      accuracy of 82%. CONCLUSIONS: Despite CA-125 AUC high correlation with the FIGO
      stage, residual disease, and patient final outcome, the main interest of CA-125
      AUC calculation is to evaluate the treatment efficacy and to foresee a full
      chemotherapy response. Further studies should be carried out before extrapolating
      these results to other data sets.

PMID- 15863157
TI  - The impact of molar pregnancy on psychological symptomatology, sexual function,
      and quality of life.
AB  - BACKGROUND: Molar pregnancy is an unusual complication of pregnancy whereby
      abnormal placental tissue proliferates in the absence of a fetus. There is
      usually a protracted follow-up period where pregnancy is contra-indicated. Whilst
      the medical outcomes of the disease have been well explored, limited data have
      evaluated the impact on psychological symptomatology, sexual function, and
      quality of life. METHODS: Institutional ethics approval and individual consent
      were obtained. All women listed on the hospital molar pregnancy register
      receiving active follow-up (n = 102) and a random sample of women who had been
      registered in the previous 30 years (n = 56) were sent a postal survey outlining
      the purpose of the study and an invitation to participate. Questionnaires
      included the Hospital Anxiety and Depression Scale (HADS), Satisfaction with Life
      Scale (SWLS), and Sexual History Form 12 (SHF-12). RESULTS: The response rate was
      54%. The key findings were that 60%, 55%, and 18% of women scored > or =10 on the
      total HADS, > or =8 on HADS-A, and >8 on HADS-D, respectively. The presence of
      children played a protective role and was associated with significantly better
      psychological function and quality of life. SWLS were in the lower end of ranges
      reported for community controls (mean of 23.9). Chemotherapy had an adverse
      impact on quality of life ratings (SWLS for chemotherapy yes = 21.7, no = 25).
      Sexual dysfunction was similar to community samples and was independent of age,
      time since diagnosis, chemotherapy requirement, and presence of children.
      Qualitative results complemented the quantitative data with similar emotional
      themes identified as well as issues related to the medical condition, care, and
      support networks. CONCLUSION: Women with a molar pregnancy may benefit from a
      multidisciplinary approach to management that addresses their psychological and
      sexual needs in addition to medical aspects of care.

PMID- 15863158
TI  - Transforming growth factor beta receptor I polyalanine repeat polymorphism does
      not increase ovarian cancer risk.
AB  - OBJECTIVES: It has been suggested that the 6A allele of the type I TGFbeta
      receptor (TGFbetaR1) polyalanine repeat tract polymorphism may increase
      susceptibility to various types of cancer including ovarian cancer. METHODS: The
      TGFbetaR1 polyalanine polymorphism was genotyped in 588 ovarian cancer cases and
      614 controls from a population-based case-control study in North Carolina.
      RESULTS: Significant racial differences in the frequency of the 6A allele were
      observed between Caucasian (10.7%) and African-American (2.4%) controls (P <
      0.001). One or two copies of the 6A allele of the TGFbetaR1 polyalanine
      polymorphism was carried by 18% of all controls and 19% of cases, and there was
      no association with ovarian cancer risk (OR = 1.07, 95% CI 0.80-1.44). The odds
      ratio for 6A homozygotes was 1.81 (95% CI 0.655.06), but these comprised only
      0.98% of controls and 1.70% of cases. CONCLUSIONS: The 6A allele of the TGFbetaR1
      polyalanine polymorphism does not appear to increase ovarian cancer risk. Larger
      studies would be needed to exclude the possibility that the small fraction of
      individuals who are 6A homozygotes have an increased risk of ovarian or other
      cancers.

PMID- 15863159
TI  - A population-based study of racial and ethnic differences in survival among women
      with invasive cervical cancer: analysis of Surveillance, Epidemiology, and End
      Results data.
AB  - OBJECTIVE: The incidence of cervical cancer is higher in Hispanic than in non
      Hispanic or African American women in the United States, but few studies have
      examined differences in survival between these groups. The objective of this
      study was to examine racial/ethnic differences in survival after diagnosis with
      invasive cervical cancer in a population-based sample of patients while adjusting
      for patient and tumor characteristics and treatment types. METHODS: We identified
      7267 women (4431 non-Hispanic Caucasians, 1830 Hispanic Caucasians, and 1006 non
      Hispanic African Americans) diagnosed with primary invasive cervical cancer from
      1992 to 1996 (with follow-up through 2000) from the Surveillance, Epidemiology
      and End Results (SEER) Program. Kaplan-Meier and Cox proportional hazards
      survival methods were used to assess differences in survival by race/ethnicity.
      RESULTS: After adjusting for age at diagnosis, histology, stage, first course of
      cancer-directed treatment (surgery and radiation therapy), and SEER registry,
      Hispanic Caucasian women were at 26% decreased risk of death from any cause
      (hazard ratio (HR) = 0.74, 95% confidence interval (CI): 0.66-0.83) and non
      Hispanic African American women were at 19% increased risk of death (HR = 1.19,
      95% CI: 1.06-1.33) compared to non-Hispanic Caucasian women over the follow-up
      period. CONCLUSION: Analysis of population-based SEER data indicates significant
      survival differences by race/ethnicity for women with invasive cervical cancer.
      Hispanic Caucasian women in SEER had improved survival compared to non-Hispanic
      Caucasian or non-Hispanic African American women.

PMID- 15863160
TI  - Immunization with adenoviral vectors carrying recombinant IL-12 and E7 enhanced
      the antitumor immunity to human papillomavirus 16-associated tumor.
AB  - OBJECTIVE: Human papillomavirus (HPV) infection play a significant role in
      cervical carcinogenesis, and HPV oncoprotein E7 has important functions in the
      formation and maintenance of cervical cancers. Interleukin-12 (IL-12) has been
      reported to induce cellular immune responses, and has also been demonstrated to
      suppress the growth of tumors and the expression of E7. Here, we investigate the
      utility of adenovirus E7 (AdE7) and adenovirus IL-12 (AdIL-12) for protection
      against TC-1 tumor using an animal model. METHODS: The antitumor effects induced
      by AdIL-12 and/or E7 were assessed by measurements of tumor size. E7-specific
      antibody and INF-gamma production in sera were measured, as were T-helper cell
      proliferative responses. Cytotoxic T-lymphocytes (CTL) and T cell subset
      depletion studies were also performed. RESULTS: Infection of tumor sites with a
      combination of AdIL-12 and AdE7 resulted in an antitumor effect which was
      significantly more profound than that which resulted from singular infections
      with either AdIL-12 or AdE7. Combined infection resulted in regression of 9-mm
      sized tumors in approximately 80% of our experimental animals as compared to the
      PBS group. Serum levels of E7-specific antibody and INF-gamma production, as well
      as T-helper cell proliferative responses, were found to be significantly higher
      in coinfected with AdIL-12 and AdE7 group than in single infection with either
      AdIL-12 or AdE7 group. CTL responses only exhibited by the AdIL-12 and AdE7
      coinjected group suggested that these tumor suppression effects were mediated
      primarily by CD8+ and, to a lesser degree, by CD4+ T cells. CONCLUSION: Combined
      injection with adenovirus carrying IL-12 and E7 induced significant antitumor
      immunity against TC-1 tumors. They may prove useful in clinical applications for
      the treatment of HPV-associated tumors.

PMID- 15863161
TI  - The functional assessment of cancer-vulvar: reliability and validity.
AB  - OBJECTIVES: To assess the reliability and validity of the Functional Assessment
      of Cancer Therapy-Vulvar (FACT-V). METHODS: Seventy-seven patients treated
      between January 1996 and January 2001 for cancer of the vulva completed the FACT
      V, the Eastern Cooperative Oncology Group Performance Status Rating (ECOG-PSR)
      and the Hospital Anxiety and Depression Scale (HADS) once, 20 consecutive
      patients treated between February 2001 and October 2001 completed the
      questionnaires twice, once before surgery and at 2 months follow-up. The FACT-V
      scores were compared by patients' performance status, FIGO stage, recurrence, and
      age, and correlated to the HADS scores. Changes in the FACT-V from baseline to 2
      months follow-up were evaluated to establish FACT-V's responsiveness to change.
      RESULTS: The FACT-V's internal consistency was adequate (Chronbach's alpha range,
      0.75 to 0.92). Patients with lower performance status, higher FIGO-stage or
      recurrent disease received lower FACT-V scores, indicating discriminant validity.
      The correlation between the FACT-V and the HADS were in the expected direction,
      indicating convergent and divergent validity. From pre- to post-surgery, scores
      in nine out of fifteen items of the vulvar cancer-specific subscale improved,
      while those of five items declined, indicating sensitivity of the vulvar cancer
      specific items to changes in patients' well-being. CONCLUSIONS: The newly
      developed FACT-V provides a reliable and valid assessment of the quality of life
      of women with vulvar cancer. It can be used as a short measure of quality of life
      within research studies, and to facilitate communication about quality of life
      issues in clinical practice.

PMID- 15863162
TI  - Neoadjuvant gemcitabine and cisplatin followed by radical surgery in (bulky)
      squamous cell carcinoma of cervix stage IB2.
AB  - OBJECTIVES: This study aimed to evaluate the efficacy and toxicity of gemcitabine
      in combination with cisplatin as neoadjuvant therapy in patients with cervical
      carcinoma stage IB2. PATIENTS AND METHODS: Chemotherapy-naive patients with
      histologic diagnosis of squamous cell cervical carcinoma staged as IB2 were
      treated with 2 cycles of cisplatin (70 mg/m(2) on day 1) and gemcitabine (1000
      mg/m(2) on days 1 and 8), given every 21 days. After chemotherapy, patients
      underwent radical hysterectomy and pelvic lymphadenectomy. Patients judged to
      have a non-resectable disease were treated with standard pelvic radiation.
      RESULTS: Between September 2000 to March 2004, 28 patients were enrolled in the
      study, of which 27 were evaluable for efficacy and toxicity. The mean age was 39
      years (30-55). The overall clinical response rate was 88.9% (24/27), with
      complete response (CR) in 9/27 patients (33.3%) and partial response in 15/27
      patients (55.5%). Three patients (11.1%) did not respond and nobody progressed. A
      pathological CR was noted in 2 of 24 patients who underwent radical surgery. The
      3 non-responding patients were subsequently treated with radiation and achieved
      CR. Grades 3 or 4 neutropenia, anemia, or thrombocytopenia was observed in 18.5%,
      7.4%, and 3.7% patients respectively. Non-hematological toxicity was mild except
      grade 3 nausea/vomiting in 18.5% patients. At median follow-up time of 36.7
      months (range 7-51 months), the 3-year survival was 88.9%. CONCLUSION:
      Neoadjuvant treatment with gemcitabine/cisplatin combination for patients with
      cervical cancer (stage IB2) appears encouraging, with manageable and acceptable
      toxicity profile.

PMID- 15863163
TI  - Chromosomal alterations in low-grade endometrial stromal sarcoma and
      undifferentiated endometrial sarcoma as detected by comparative genomic
      hybridization.
AB  - OBJECTIVE: Endometrial stromal sarcomas (ESS) are very rare neoplasms
      constituting less than 0.5% of all malignant uterine tumors. The aim of the
      present study was to characterize the karyotypic abnormalities in these malignant
      mesenchymal tumors and to find specific chromosomal aberrations with eventual
      correlation with histologic grades. METHODS: Twelve cases of endometrial stromal
      sarcomas consisting of nine low-grade ESS and three undifferentiated endometrial
      sarcomas (UES) were investigated by comparative genomic hybridization (CGH).
      RESULTS: Ten of the twelve cases (83.3%) displayed chromosomal gains or losses.
      Deletions occurred more frequently than gains (63.4% versus 36.6%). In low-grade
      ESS, gains on 1, 6q, 9q, 16p, 19, 20q, 22q and losses on 2, 4q, 6, 7, 11q, 13q,
      15q, 16q, 20p, X were detected. CGH with UES exhibited gains on 2q, 4q, 6q, 7p,
      9q, 20q and losses on 3q, 10p, 14q. One low-grade ESS and one UES did not reveal
      any chromosomal aberration. CONCLUSIONS: Chromosomal aberrations in endometrial
      sarcomas are heterogeneous and do not clearly correlate with the histologic
      grades. There is no increased accumulation of aberrations from low-grade ESS to
      UES. Despite the karyotypic variations, chromosomal deletion on 7p was the most
      common finding (55.6%) in low-grade ESS and may play a role in tumor development
      and progression.

PMID- 15863165
TI  - Rectus abdominis myocutaneous and myoperitoneal flaps for neovaginal
      reconstruction after radical pelvic surgery: comparison of flap-related
      morbidity.
AB  - PURPOSE: To compare flap-specific complications of rectus abdominis myocutaneous
      (RAM) and myoperitoneal (RAMP) flap neovagina reconstructions performed
      concurrently with radical pelvic procedures. MATERIALS AND METHODS: Retrospective
      single institution chart review of all patients with RAM or RAMP flap neovaginal
      reconstructions performed on a Gynecologic Oncology service, 1988-2003. Analysis
      for associations with flap-specific morbidity was performed. RESULTS: Neovaginal
      reconstructions comprised 32 RAM and 7 RAMP flaps. Twenty-two (69%) RAM patients
      underwent total pelvic exenteration compared to 1 (14%) RAMP patient (P < 0.013).
      Overall, 33 (85%) of the patient population had previously been treated with
      radiation. Flap-specific complications developed in 12 (32%) RAM versus 4 (57%)
      of the RAMP patients (P > 0.1). Donor site complications and incisional hernias
      were increased in RAMP patients (both P < 0.03), with trends for increasing risk
      of vaginal stricture/stenosis and superficial wound separations (both P < 0.1).
      Complete vaginal stenosis developed in only 1 (3%) RAM versus 3 (43%) RAMP
      patients. Furthermore, 3 RAMP patients developed complete stenosis when the
      vaginal defect was circumferential and involved >65% of the vagina while this did
      not occur in 22 similar RAM patients (P < 0.0005). Only patients with partial
      longitudinal defects maintained vaginal patency after RAMP flap. Fifteen (58%) of
      26 patients surviving >12 months reported coitus, with no significant difference
      between the groups. CONCLUSIONS: When there is circumferential loss of the upper
      2/3 of the vagina. RAMP flaps are not suitable for neovaginal reconstruction
      after radical pelvic surgery because of an increased risk of vaginal stenosis
      compared to RAM flaps. Patients with partial longitudinal vaginal defects,
      however, may have successful neovaginal reconstruction with RAMP flaps.

PMID- 15863164
TI  - Sentinel node detection in cervical cancer with (99m)Tc-phytate.
AB  - OBJECTIVES: The aim of this study was to investigate the feasibility of sentinel
      lymph node (SLN) identification using radioisotopic lymphatic mapping with
      technetium-99 m-labeled phytate in patients undergoing radical hysterectomy with
      pelvic lymphadenectomy for treatment of early cervical cancer. METHODS: Between
      July 2001 and February 2003, 56 patients with cervical cancer FIGO stage I (n =
      53) or stage II (n = 3) underwent sentinel lymph node detection with preoperative
      lymphoscintigraphy ((99m)Tc-labeled phytate injected into the uterine cervix, at
      3, 6, 9, and 12 o'clock, at a dose of 55-74 MBq in a volume of 0.8 ml) and
      intraoperative lymphatic mapping with a handheld gamma probe. Radical
      hysterectomy was aborted in three cases because parametrial invasion was found
      intraoperatively and we performed only sentinel node resection. The remaining 53
      patients underwent radical hysterectomy with complete pelvic lymphadenectomy.
      Sentinel nodes were detected using a handheld gamma-probe and removed for
      pathological assessment during the abdominal radical hysterectomy and pelvic
      lymphadenectomy. RESULTS: One or more sentinel nodes were detected in 52 out of
      56 eligible patients (92.8%). A total of 120 SLNs were detected by
      lymphoscintigraphy (mean 2.27 nodes per patient) and intraoperatively by gamma
      probe. Forty-four percent of SLNs were found in the external iliac area, 39% in
      the obturator region, 8.3% in interiliac region, and 6.7% in the common iliac
      area. Unilateral sentinel nodes were found in thirty-one patients (59%). The
      remaining 21 patients (41%) had bilateral sentinel nodes. Microscopic nodal
      metastases were confirmed in 17 (32%) cases. In 10 of these patients, only SLNs
      had metastases. The 98 sentinel nodes that were negative on hematoxylin and eosin
      were submitted to cytokeratin immunohistochemical analysis. Five (5.1%)
      micrometastases were identified with this technique. The sensitivity of the
      sentinel node was 82.3% (CI 95% = 56.6-96.2) and the negative predictive value
      was 92.1% (CI 95% = 78.6-98.3). The accuracy of sentinel node in predicting the
      lymph node status was 94.2%. CONCLUSION: Preoperative lymphoscintigraphy and
      intraoperative lymphatic mapping with (99m)Tc-labeled phytate are effective in
      identifying sentinel nodes in patients undergoing radical hysterectomy and to
      select women in whom lymph node dissection can be avoided.

PMID- 15863166
TI  - Expression of Apaf-1 in cervical cancer correlates with lymph node metastasis but
      not with intratumoral hypoxia.
AB  - OBJECTIVES: The aim of this study was to investigate the expression of the
      proapoptotic protein Apaf-1 in cervical cancers. Moreover, we studied its
      correlation to intratumoral pO(2) and to clinico-pathological parameters.
      METHODS: 86 patients with cervical cancer were subjected to intratumoral pO(2)
      measurement with the Eppendorf electrode. From these patients, cervical cancer
      tissue was used for immunohistochemistry with an anti-Apaf-1 antibody. RESULTS:
      Apaf-1 is expressed in cervical cancer. Cervical cancers with strong or moderate
      Apaf-1 expression had significantly less lymph node metastases at time of surgery
      than tumors with weak or negative Apaf-1 expression (P = 0.022). There was no
      significant correlation between Apaf-1 expression and intratumoral pO(2), pT
      stage, FIGO stage, lymphovascular space involvement, and grade. CONCLUSIONS: Loss
      of Apaf-1 expression may represent a marker of aggressive tumor behavior since it
      correlates significantly with the occurrence of lymph node metastasis in cervical
      cancer.

PMID- 15863167
TI  - Feasibility of RNA collection for micro-array gene expression analysis in the
      treatment of cervical carcinoma: a scientific correlate of RTOG C-0128.
AB  - PURPOSE: To determine the feasibility of RNA collection in a multi-institutional
      cooperative group setting to be utilized for micro-array gene expression
      analysis, and to describe the methodology. METHODS: RTOG C0128, a phase I-II,
      protocol was designed to look at the safety and efficacy of external beam
      radiation therapy to 45 Gy with concomitant 5-FU and cisplatin chemotherapy,
      brachytherapy to deliver 85 Gy to point A, and Celecoxib at 400 mg twice daily
      for 1 year. Patients had the option of participating in a tissue collection
      portion of the protocol to be utilized for micro-array gene expression analysis
      before treatment and at the time of the first implant. RNA quality was determined
      by two parameters: the absorbance ratio at 260 nm/280 nm, and by the ratio of the
      integrated peak of 28S RNA to 18S RNA after gel electrophoresis. RESULTS: From
      August 2001 to March 2004, 84 patients were accrued to the trial, and tissue was
      obtained prior to initiation of therapy on 34 patients (40%). FIGO stages for the
      patients who provided tissue were IB (23%), II (57%), and IIIA-IVA (20%).
      Additionally, biopsies were obtained at the time of the first implant from 22 of
      the accrued patients making paired samples available on 26% for RNA extraction
      and micro-array gene expression analysis. The mean +/- SEM amount of tissue
      obtained pretreatment was 97 +/- 13 mg compared with 51 +/- 8 mg for tissue
      obtained at the time of the first implant (P = 0.009). The mean total RNA
      extracted from the samples prior to treatment was 119 +/- 19 microg versus 35 +/-
      6 microg at the time of the first procedure (P = 0.001). The RNA quality was
      assessed via the absorbance ratio at 260 nm divided by 280 nm. The mean values
      pretreatment and at first implant were 1.87 +/- 0.07 versus 1.66 +/- 0.11,
      respectively (P = 0.002); however, the integrated peak of 28S RNA to 18S RNA
      after gel electrophoresis was not significantly different (P = 0.26).
      CONCLUSIONS: RNA extraction for gene expression analysis can be successfully
      performed in the multi-institutional cooperative group setting. Fresh tissue
      samples were obtained on 40% of accrued patients prior to treatment. The amount
      of biopsy material and the quantity of RNA extracted were greater prior to
      treatment compared with the first implant. The quality of RNA was superior prior
      to treatment as measured by the ratio of absorbance at 260/280 nm. These results
      indicate that gene expression analysis is feasible in the cooperative group
      setting utilizing amplification techniques for the RNA. Hopefully, this will
      allow for improvement in prognosis, therapeutic development, and correlation with
      acute and late toxicities in patients with cancer.

PMID- 15863168
TI  - Comparison of type-specific human papillomavirus data from self and clinician
      directed sampling.
AB  - OBJECTIVE(S): To compare the type-specific human papillomavirus (HPV) recovery
      from physician and patient-collected samples. METHODS: Three hundred thirty-four
      (334) women attending colposcopy clinics in three countries were enrolled in this
      cross-sectional study. Cervicovaginal samples were collected by patients and
      physicians and processed with polymerase chain reaction and reverse line blot
      genotyping. McNemar's Chi-squared tests and Kappa statistics were utilized to
      determine statistical associations between physician- versus patient-collected
      samples. RESULTS: Oncogenic HPV infection was identified in 23.2% of patient
      collected specimens compared to 34.9% of physician-collected specimens. Physician
      sampling detected significantly more infections with type 16 and 52 than did self
      sampling and significantly more oncogenic HPV infection overall. For non
      oncogenic HPV detection, there was no statistical difference between physician-
      and patient-collected samples. CONCLUSION(S): Patient sampling for HPV using a
      single vaginal brush does not identify all oncogenic HPV subtypes.

PMID- 15863169
TI  - Secondary chemotherapy for high-risk gestational trophoblastic neoplasia.
AB  - OBJECTIVE: To determine the efficacy of secondary chemotherapy after failure of
      initial treatment for high-risk gestational trophoblastic neoplasia. METHODS:
      Twenty-six patients with high-risk gestational trophoblastic neoplasia based on
      WHO criteria who failed primary treatment or relapsed from remission and received
      secondary chemotherapy were identified from the records of the Brewer
      Trophoblastic Disease Center. Initial chemotherapy consisted of etoposide, high
      dose methotrexate with folinic acid, actinomycin D, cyclophosphamide and
      vincristine (EMA-CO) in 10 patients and methotrexate/actinomycin D-based
      chemotherapy without etoposide in 16 patients. Secondary chemotherapy consisted
      mainly of platinum-etoposide combinations with methotrexate and actinomycin D
      (EMA-EP), bleomycin (BEP), or ifosfamide (VIP, ICE). Adjuvant surgery and
      radiotherapy were used in selected patients. Clinical response and survival as
      well as factors affecting survival were analyzed retrospectively. RESULTS: The
      overall survival has 61.5% (16/26). Of the 10 patients who failed primary
      treatment with EMA-CO, 9 (90%) had complete clinical responses to secondary
      chemotherapy with EMA-EP (3) or BEP (6), and 6 (60%) were placed into lasting
      remission. Of the 16 patients who failed primary treatment with
      methotrexate/actinomycin D-based chemotherapy without etoposide, 10 (63%) had
      complete clinical responses to BEP (8), VIP (1) and ICE (1), and 10 (63%)
      achieved long-term remission. Adjuvant surgical procedures were performed on 15
      patients as a component of their therapy; eight (73%) of 11 patients who
      underwent hysterectomy, five (62%) of eight patients who had pulmonary
      resections, and one patient who had wedge resection of resistant choriocarcinoma
      from the uterus survived. Survival was significantly influenced by both hCG level
      at the start of secondary therapy and sites of metastases. CONCLUSION: Patients
      with persistent or recurrent high-risk gestational trophoblastic neoplasia who
      develop resistance to methotrexate-containing treatment protocols should be
      treated with drug combinations employing a platinum agent and etoposide with or
      without bleomycin or ifosfamide.

PMID- 15863170
TI  - Systemic therapy for advanced uterine sarcoma: a systematic review of the
      literature.
AB  - OBJECTIVE: To conduct a systematic review of the literature regarding the
      systemic treatment of advanced uterine sarcoma and provide an evidence-based
      summary of the available literature. METHODS: MEDLINE, EMBASE, and the Cochrane
      Library databases were searched. "Uterine sarcoma," "leiomyosarcoma," "mixed
      mesodermal tumor," "chemotherapy," and "systemic therapy" were combined with the
      search terms for study designs. RESULTS: Three randomized controlled trials and
      24 prospective phase II trials were included in the systematic review. In a
      randomized trial of doxorubicin versus doxorubicin plus cyclophosphamide for
      advanced or recurrent uterine sarcoma, doxorubicin produced an overall response
      rate (RR) of 19% and median survival of 11.6 months, which was similar to the
      response with combination chemotherapy (RR 19%, median survival 10.9 months). A
      randomized trial comparing ifosfamide plus cisplatin versus ifosfamide alone in
      mixed mesodermal tumors showed a significant improvement in RR and progression
      free survival with the combination compared with ifosfamide alone, however, the
      combination was associated with increased toxicity including death. A randomized
      trial comparing doxorubicin to doxorubicin with dacarbazine in women with
      advanced or recurrent uterine sarcoma demonstrated a significantly higher RR with
      the combination (P < 0.05), but no significant difference in survival.
      CONCLUSIONS: Offering palliative chemotherapy to patients with advanced,
      unresectable uterine sarcoma who are symptomatic from this disease is a
      reasonable decision. Doxorubicin is an option for women with advanced uterine
      sarcoma. The combination of cisplatinum and ifosfamide is also an option for
      women with metastatic mixed mesodermal tumors; however, this combination is
      associated with significant toxicity when compared to ifosfamide alone.

PMID- 15863171
TI  - Futility: clinical decisions at the end-of-life in women with ovarian cancer.
AB  - OBJECTIVE: The purpose of this article is to provide a review of the clinical
      meaning of futility, discuss current normative uses of futility assessments and
      propose guidelines for clinicians to use in dialogue regarding treatment
      decisions for patients with advanced ovarian cancers. METHODS: We performed a
      MEDLINE literature search of relevant clinical articles for this review that
      discussed futility and the application to women with ovarian cancer. RESULTS:
      Medical futility refers to treatments that serve no physiologic, quantitative or
      qualitative meaningful purpose. Despite the growth in options focused on symptom
      management rather than disease eradication, including hospice programs and the
      more recent development of palliative care programs, there is evidence that many
      patients continue to receive aggressive interventions, including chemotherapy,
      until days before their death. While the legal and moral acceptability of
      treatment limitation is well established, clarity in establishing goals of care,
      timing of the transition from cure to palliation and communication of specific
      decisions to withhold further aggressive interventions remain problematic for
      both patients and clinicians. CONCLUSIONS: There continues to be a distinct need
      for both better understanding of the dynamics of patient choice and increased
      education of physicians in addressing end-of-life care planning. It is essential
      that we continue to test specific communication and supportive interventions that
      will improve our ability to help patients avoid the burden of futile therapy
      while maintaining hope.

PMID- 15863172
TI  - Is the assumed natural history of vulvar intraepithelial neoplasia III based on
      enough evidence? A systematic review of 3322 published patients.
AB  - OBJECTIVE: To establish the true natural history of VIN III from literature data.
      METHODS: In a systematic review, data of women with VIN III indexed in several
      computer databases were pooled. The effect of treatment was correlated with
      recurrences and progression of VIN III. RESULTS: Ninety-seven articles met the
      inclusion criteria. Data of 3322 patients were available. The mean age at
      diagnosis of VIN III was 46. This decreased over time, although not significantly
      (P = 0.08). Recurrences were seen as often after local excision as after
      vulvectomy. The percentage of recurrences was lower, but not absent, after free
      surgical margins than after involved surgical margins (P < 0.001). 6.5% of the
      3322 patients progressed to an invasive vulvar carcinoma. Occult carcinomas were
      diagnosed in 3.2% of patients and 3.3% carcinomas were diagnosed during follow
      up. The mean age at diagnosis of invasive vulvar carcinoma was 52 years. Nine
      percent of 88 untreated patients progressed in 12 to 96 months to invasive vulvar
      carcinoma. Only 1.2% of the 3322 patients showed complete regression, mostly
      during the first 10 months after diagnosis, 41% of which was related to
      pregnancy. CONCLUSION: Evidence exists that VIN III may progress to invasive
      vulvar carcinoma. However, the available literature suggests that the progression
      rate to invasive vulvar carcinoma is low. The incidence of invasion as found in
      this systematic review is probably even too high, because overreporting of
      (micro)invasive cases cannot be excluded. Only a prospective registration using a
      standardized pathology examination will provide information about the real
      natural history of VIN III.

PMID- 15863173
TI  - Ovarian metastasis in a nulliparous woman with endometrial adenocarcinoma failing
      conservative hormonal treatment.
AB  - BACKGROUND: There have been several reports about successful fertility-preserving
      treatment of endometrial carcinoma with subsequent pregnancy. However,
      conservative hormonal treatment for early-stage endometrial cancer still entails
      some risk. CASE: We present a 36-year-old nulliparous woman, initially diagnosed
      as clinical stage IA, grade 1 endometrial adenocarcinoma, receiving 6-month
      conservative treatment with remission achieved at 4 months from diagnosis.
      Recurrence at the endometrium was documented at the end of treatment. She
      underwent a definitive surgery including total hysterectomy, bilateral salpingo
      oophorectomy, and pelvic lymph node dissection. The final pathology revealed well
      differentiated endometrioid adenocarcinoma with inner one-third myometrial
      invasion and right ovarian metastasis. CONCLUSION: This case report signals a
      warning that negative preoperative imaging studies are not reassuring for a
      relapsing low-grade, early-stage endometrial carcinoma failing conservative
      treatment.

PMID- 15863174
TI  - A rare female genital tract tumor: benign granular cell tumor of vulva: case
      report and review of the literature.
AB  - BACKGROUND: The granular cell tumor (GCT) of vulva is a rare female genital tract
      tumor. CASE: A 59-year-old female was incidentally noted to have a 1-cm sized
      lump in her left labium majus that subsequently increased in size to
      approximately 4 cm. The mass was totally excised under general anesthesia. Her
      postoperative follow-up was uneventful. Histologic examination of the tumor
      showed sheets and clusters of infiltrating tumor cells with morphologic features
      consistent with granular cell tumor. CONCLUSION: Although benign and slow
      growing, it has a tendency for recurrence and can cause morbidity and mortality
      when presenting with multicentric or multiple organ involvement due to the lack
      of effective systemic therapy. Therefore, clinicians and pathologists should be
      aware of its clinical and histopathologic features.

PMID- 15863175
TI  - Widespread lymph node metastases in a young woman with FIGO stage IA1 squamous
      cervical cancer.
AB  - BACKGROUND: Lymphatic and hematologic metastases are rare in microinvasive
      cervical cancers (FIGO stage IA1), supporting a role for conservative treatment.
      Cervical conization followed by prolonged surveillance is an accepted treatment
      in patients with low-risk features and negative surgical margins. This option is
      particularly appealing for younger or nulliparous patients, in whom fertility may
      be highly desired. CASE: We report a case of a 22-year-old, HIV-negative female
      with stage IA1 squamous cell cervical carcinoma who was found to have bilateral
      lymph node metastases in both pelvic and para-aortic distributions after electing
      to undergo hysterectomy. CONCLUSION: Clinicians treating patients with
      microinvasive cervical cancer conservatively must be aware of the possibility of
      lymph node involvement and should consider radiological imaging to look for
      metastatic disease.

PMID- 15863176
TI  - Adenocarcinoma in situ of the cervix in pregnancy.
AB  - INTRODUCTION: The number of patients diagnosed with adenocarcinoma in situ of the
      cervix has increased in the last decade. The number of pregnant patients with
      this disease can also be expected to increase. CASES: In this report, we describe
      three patients diagnosed with adenocarcinoma in situ of the cervix during
      pregnancy. DISCUSSION: The management of adenocarcinoma in situ of the cervix may
      include procedures which present substantial risks to an ongoing pregnancy and
      more conservative management may be warranted in many instances.

PMID- 15863177
TI  - Three-dimensional ultrasound to assess the response to treatment in gynecological
      malignancies.
AB  - OBJECTIVE: To report the potential role of 3D ultrasound to assess the response
      to treatment in gynecological malignancies. METHODS: The volumes and three 3D
      power Doppler indices are measured in one case of cervix carcinoma and in one
      case of ovarian carcinoma with primary radio- and/or chemotherapy before and
      after treatment. RESULTS: After treatment, tumor volume, vascularization index
      (VI), flow index (FI), and vascularization-flow index (VFI) were reduced in both
      two cases. CONCLUSION: 3D ultrasound may provide a new method to assess the
      response to treatment in gynecological malignancies.

PMID- 15863178
TI  - Recurrence of vaginal implantation of transitional cell carcinoma of the urinary
      tract.
AB  - BACKGROUND: Vaginal recurrence of bladder carcinoma is extremely rare, with only
      two cases already reported. We have experienced a third case with the same
      characteristics of the first one, which was a vaginal recurrence with a prior
      resected urothelial vaginal tumor. CASE: An 82-year-old woman first presented in
      1994 with frequency and gross hematuria. Cystoscopic evaluation revealed a single
      superficial tumor of the bladder which was treated by endoscopic resection.
      During the following 7 years, she underwent endoscopic procedures to remove
      recurrent Ta G2 tumor. In 2002, a cystoscopy revealed a papillary lesion, and a
      physical examination demonstrated multiple papillary lesion on the vaginal wall.
      Histology of excised genital lesions showed a Grade 2 transitional cell
      carcinoma. Two years later, the patient presented with a 1-cm solitary lesion on
      the right vaginal wall, which was then excised. Histological examination showed
      high-grade transitional cell carcinoma, infiltrating the chorion of the vagina.
      CONCLUSION: Implantation of shed tumor cells in tissues during micturition or
      resection seems the only plausible cause of the first implantation. For the
      second recurrence in the vagina, the possibility is of an incomplete locally
      excision or a relapse, tied to lymphatic micro metastasis, due to involvement of
      its own lamina propia.

PMID- 15863179
TI  - A successfully treated case of primary tubal choriocarcinoma coexistent with
      viable intrauterine pregnancy.
AB  - BACKGROUND: Choriocarcinoma of the fallopian tube is extremely rare as is
      choriocarcinoma with a viable pregnancy. We present an unusual case of prima
      gravida at 33 weeks gestation that was diagnosed as having tubal choriocarcinoma
      which was successfully treated by chemotherapy. CASE: A 31-year-old prima gravida
      at 32(+3) weeks gestation was admitted complaining of dyspnea and blood tinged
      sputum. Suspecting a left adnexal malignant tumor with pulmonary metastasis,
      delivery of the baby for optimal treatment of the mother's tumor was planned.
      Cesarean delivery was performed because of induction failure. Tumorectomy with
      left salpingectomy and infracolic omentectomy was performed for a left tubal
      tumor. Microscopic findings revealed choriocarcinoma with extensive hemorrhage.
      Its FIGO stage was III and its WHO prognostic score 12, representing high risk.
      After 4 cycles of chemotherapy, serum beta-hCG level fell to the normal range.
      The patient and her baby remain disease-free 16 months after disease diagnosis.
      CONCLUSION: This is the first reported case of tubal choriocarcinoma coexistent
      with a viable pregnancy, in which the baby survived and the mother was
      successfully treated by chemotherapy.

PMID- 15863180
TI  - Vulval Keratoacanthoma: a case report.
AB  - BACKGROUND: Vulval Keratoacanthoma (KA) is very rare and its differential
      diagnosis from the commonly occurring Vulval Squamous Cell Carcinoma (SCC) is
      important to avoid overtreatment. CASE: A case of Vulval KA in a 79-year-old lady
      is reported. She presented with a 9-mm firm raised lesion on the antero-lateral
      left side of the clitoris of a few months' duration with no associated symptoms.
      The lesion was resected with clear margins and the excision site was well healed
      at her appointment 4 weeks later. CONCLUSION: We share our experience reporting
      the fifth case of a vulval KA in the world literature. Consideration to the
      occurrence of vulval KA is important to avoid both an erroneous diagnosis of
      vulval SCC and the associated consequences of radical surgery.

PMID- 15863181
TI  - Groin angiosarcoma following radiotherapy for vulvar cancer.
AB  - BACKGROUND: Angiosarcomas account for less than 2% of all sarcomas. However, they
      represent 15% of radiotherapy-induced sarcomas, usually associated to the
      treatment for breast cancer, cervical cancer, and lymphomas. CASE REPORT: We
      report the case of a 56-year-old patient who developed a soft tissue angiosarcoma
      in the right groin 25 years after receiving radiotherapy for vulvar cancer. To
      our knowledge, this is the second case reported of a soft tissue angiosarcoma
      after radiotherapy for a vulvar cancer. CONCLUSION: Postradiation sarcoma must be
      considered in patients with a history of a previous tumor when a soft tissue mass
      is seen in the previously irradiated field, especially if the latent period is
      more than 3 or 5 years. The correct histologic interpretation of such lesions is
      important because it may result in early identification of the secondary
      malignancy and may contribute to better management and improved prognosis.

PMID- 15863182
TI  - Ovarian dysgerminoma associated with Pseudo-Meigs' syndrome and functioning
      ovarian stroma: a case report.
AB  - BACKGROUND: We present the first case of an ovarian dysgerminoma complicated by
      pseudo-Meigs' syndrome. Furthermore, this is the fourth reported case of ovarian
      dysgerminoma with functioning ovarian stroma resulting elevated androgen levels
      preoperatively. CASE: A 25-year-old white female was referred to our department
      for abdominal swelling and a rapidly enlarging abdominal mass. Chest X-ray showed
      massive right pleural effusion. Abdominopelvic CT scan showed a left adnexal
      solid mass and ascites. Preoperative abnormally elevated hormone levels were as
      follows: free testosterone 7.7 pg/mL, androstenodione 13.6 ng/mL, and cortisol
      29.4 microg/dL. Left salpingo-oophorectomy and wedge resection of the right ovary
      were performed. Final histopathological investigation of the left ovary was
      dysgerminoma associated with stromal luteinization. CONCLUSION: Dysgerminoma
      should be considered in the differential diagnosis in a young patient with a
      pelvic mass, ascites, and pleural effusion and preoperative counseling should be
      directed accordingly. In addition, dysgerminomas may be accompanied by ovarian
      stromal luteinization and steroid hormone production, which occasionally result
      in chemical or clinical hyperandrogenism.

PMID- 15863183
TI  - Lower urinary tract reconstruction with ileum in the treatment of gynecologic
      malignancies.
AB  - INTRODUCTION: Advanced or recurrent gynecologic malignancies can invade or
      obstruct the lower urinary tract. If extirpation is necessary for cytoreduction
      or repair of radiation sequelae, treatment has typically involved creation of
      either an ileal conduit or a cutaneous continent urinary diversion. As an
      alternative, a more limited resection with urinary tract reconstruction using
      ileum for interposition or augmentation may allow for the preservation of
      urethral voiding. CASES: We describe the use of ileal segments for lower urinary
      tract reconstruction in the treatment of ten patients with advanced or recurrent
      gynecologic malignancies. The clinical history, surgical technique, and patient
      outcomes are reviewed. DISCUSSION: These cases demonstrate that limited bladder
      or ureteral resection with reconstruction using ileal segments may offer select
      patients preservation of urethral voiding.

PMID- 15863184
TI  - Management of an advanced ovarian cancer at 15 weeks of gestation: case report
      and literature review.
AB  - BACKGROUND: To report a case of advanced ovarian carcinoma diagnosed during
      gestation, which was managed with conservative surgery and chemotherapy until
      delivery. CASE: The patient underwent bilateral salpingo-oophorectomy,
      omentectomy, and appendectomy at 15 weeks of gestation. Six courses of
      chemotherapy with cisplatin were administered. Cesarean section followed by total
      hysterectomy were performed at 36 weeks of gestation. The male infant was 3000 g,
      Apgar score 9/9. Twenty-four months after delivery, the patient experienced
      pelvic recurrence and underwent surgery and six cycles of carboplatin and
      paclitaxel. The patient is alive with no evidence of disease. After 42 months of
      follow-up, the baby boy showed no evidence of sequelae. CONCLUSION: Medical and
      surgical management of ovarian cancer during pregnancy can be an option, although
      the risks and benefits have to be discussed with caution.

PMID- 15863185
TI  - Epithelioid leiomyosarcoma of the ovary.
AB  - INTRODUCTION: Leiomyosarcoma of the ovary is a rare lesion usually seen in
      postmenopausal women. Epithelioid leiomyosarcoma of the ovary is exceptionally
      rare, with only one previously reported case. CASE: A 42-year-old nulliparous
      woman undergoing ovulation induction presented with a left adnexal mass. An
      exploratory laparotomy was performed. Frozen section diagnosis was read as
      fibrothecoma, and an oophorectomy was performed. The final diagnosis was
      epithelioid leiomyosarcoma of the ovary. Subsequently, a staging procedure
      including hysterectomy was performed with no residual disease. DISCUSSION: This
      is an unusual case for several reasons. Most leiomyosarcomas of the ovary have
      occurred in postmenopausal women and were of advanced stage at diagnosis. Our
      case had an epithelioid histology, occurred in a premenopausal woman, and was
      confined to the ovary. The fact that the patient was undergoing ovulation
      induction at the time of diagnosis raises the question of the risk of developing
      ovarian neoplasms with these medications.

PMID- 15863186
TI  - Primary malignant vaginal melanoma treated with adriamycin and ifosfamide: a case
      report and literature review.
AB  - BACKGROUND: Vaginal melanoma is a very rare but highly malignant gynecological
      disease, usually diagnosed in postmenopausal woman. The prognosis tends to be
      poor and it is associated with high rate of recurrence and short survival rates.
      CASE: The following paper describes a case report regarding a 72-year-old woman
      with a locally advanced malignant melanoma. The previous erroneous
      histopathological diagnosis was leiomyosarcoma. She underwent chemotherapy with 3
      courses of doxorubicin and ifosfamide. The diagnosis of malignant melanoma was
      obtained after a repeated biopsy and further pathological investigations. She
      later underwent radical surgery and 2 additional cycles of the same chemotherapy.
      At present, 7 months after the last cycle, the patient was locally disease-free,
      but developed brain metastases, requiring chemotherapy treatment. CONCLUSION: In
      view of poor survival, this chemotherapy regimen may be an interesting
      alternative to the traditional treatment of vaginal melanoma.

PMID- 15863187
TI  - Celiac disease presenting as a paraneoplastic syndrome in a patient with
      synchronous endometrial and ovarian cancers.
AB  - OBJECTIVE: Celiac disease is characterized by gluten intolerance and commonly
      manifests with unexplained diarrhea, abdominal distention and weight loss.
      Infrequently, patients present with vague, non-specific symptoms which often
      delay diagnosis and treatment. CASE: A 52-year-old female with a history of
      synchronous endometrial and ovarian cancers, previously treated with surgical
      resection, staging and pelvic irradiation, presented with progressive
      paresthesias in her extremities. Extent of disease work-up was unremarkable.
      Neurologic evaluation suggested celiac disease which was later proven by duodenal
      biopsy. CONCLUSION: The development of new or worsening neurologic symptoms in
      the cancer patient requires a thorough evaluation especially to exclude
      metastatic disease and/or paraneoplastic syndromes. Once neoplastic processes are
      excluded, celiac disease should be considered in the differential diagnosis of
      patients with unexplained neurologic dysfunction.

PMID- 15863188
TI  - Laparoscopic abdominal radical trachelectomy.
AB  - BACKGROUND: Radical trachelectomy is a fertility preserving alternative for young
      women with early stages of cervical cancer. Currently, a technique of abdominal
      radical approach is used in a few centres. With growing availability of
      laparoscopy, a novel technique of laparoscopic radical trachelectomy might be an
      alternative. CASE: Presented is one case of laparoscopic pelvic lymphadenectomy
      with radical trachelectomy in young woman with IB cervical cancer. No
      intraoperative or postoperative complications occurred. Operation time reached
      250 min, estimated blood loss was 250 ml. Limited follow-up of 9 months was
      uneventful and patient indicates normal menstrual pattern and satisfactory sexual
      intercourse. CONCLUSION: Laparoscopic abdominal radical trachelectomy with pelvic
      lymphadenectomy might be an alternative technique in the treatment of early
      stages cervical cancer in patients who desire future pregnancy. The procedure is
      in principle identical to the standard abdominal radical hysterectomy. Centres
      practising laparoscopic radical hysterectomy can adopt the technique without any
      special surgical training.

PMID- 15863189
TI  - The administration of chemotherapy in a patient with Charcot-Marie-Tooth and
      ovarian cancer.
AB  - BACKGROUND: Standard adjuvant chemotherapy for epithelial ovarian carcinoma most
      commonly consists of a combination of carboplatin with a taxane derivative.
      However, treatment-related side effects such as peripheral neuropathy and
      neutropenia can be debilitating and in certain patient populations alterations
      may need to be considered. CASE: We describe a case of a patient with epithelial
      ovarian carcinoma who had pre-existing peripheral neuropathy secondary to Charcot
      Marie-Tooth Disease (CMT). She developed a distal sensory and motor neuropathy
      after her first treatment with carboplatin and paclitaxel and was unable to walk,
      write, or drive. Upon transfer of care to our center, we changed her taxane to
      docetaxel and her symptoms improved dramatically. We discuss the outcome of her
      treatment and the effects of paclitaxel on her underlying peripheral neuropathy.
      CONCLUSION: Patients with Charcot-Marie-Tooth Disease who require chemotherapy
      may not be able to tolerate the neurotoxic side effects of paclitaxel-based
      chemotherapy. Consideration of alternative, less neurotoxic treatment regimens
      containing docetaxel may be considered.

PMID- 15863190
TI  - Occult choriocarcinoma discovered by positron emission tomography/computed
      tomography imaging following a successful pregnancy.
AB  - BACKGROUND: Positron emission tomography (PET) is commonly used to detect occult
      or recurrent malignancy, including tumors of the female genital tract. Recently,
      there have been reports of PET scans used in patients with Gestational
      Trophoblastic Disease (GTD). CASE: A 22-year-old female presented with vaginal
      bleeding and elevated beta-hCG 7 months after a spontaneous vaginal delivery of a
      healthy infant. She had a history of molar pregnancy and persistent GTD requiring
      multi-agent chemotherapy. Metastatic evaluation with computed tomography and
      magnetic resonance imaging showed no evidence of GTD. A positron emission
      tomography/computed tomography (PET/CT) scan revealed a focus of metabolic
      activity in the left pelvis. The patient underwent an exploratory laparotomy that
      revealed metastatic choriocarcinoma in the left broad ligament. CONCLUSION:
      PET/CT may be useful in the evaluation of occult choriocarcinoma when
      conventional imaging fails to identify metastatic disease.

PMID- 15863191
TI  - Lymphoepithelioma-like carcinoma of the uterine cervix: absence of Epstein-Barr
      virus, but presence of a multiple human papillomavirus infection.
AB  - BACKGROUND: Cervical lymphoepithelioma-like carcinoma (LELC) is a rare variant of
      squamous cell carcinoma of the cervix. Association with Epstein-Barr virus (EBV)
      is still controversial. EBV has been demonstrated in Asian women with cervical
      LELC. In Western women, human papillomavirus (HPV) might play a role in the
      etiology. CASE: We describe a 44-year-old Caucasian woman with a
      lymphoepithelioma-like carcinoma of the cervix without EBV, but in the presence
      of multiple HPV infection. CONCLUSION: Our case supports a possible different
      pathway of development of cervical LELC in Western women as compared to Asian
      women.

PMID- 15863192
TI  - De novo growth of a large preperitoneal lipoleiomyoma of the abdominal wall.
AB  - BACKGROUND: Extrauterine lipoleiomyomas are an uncommon finding, especially in
      the preperitoneum. These benign tumors have been attributed to seeding after
      surgical fibroid resection, exogenous hormonal therapy, or major disturbances in
      glucose metabolism. CASE: We are reporting the case of a postmenopausal woman
      without any history of gynecological surgery, hormonal therapy, or significant
      metabolic abnormality who developed a large, symptomatic, preperitoneal
      lipoleiomyoma requiring resection. The patient had an uneventful recovery with
      full resolution of her symptoms. CONCLUSION: Our case relates the first
      description to our knowledge of the de novo growth of a large lipoleiomyoma in an
      incisional umbilical scar independent of gynecological pathology or hormonal
      influence.

PMID- 15863193
TI  - Successful salvage therapy of resistant gestational trophoblastic disease with
      ifosfamide and paclitaxel.

PMID- 15863194
TI  - Use of biological response modifiers to enhance the action of Rituximab.

PMID- 15863195
TI  - Complex and simple.

PMID- 15863196
TI  - Trying to improve clinical outcome in AML: lessons from negative trials.

PMID- 15863197
TI  - The rationale engineering of BCR/ABL blockers: an answer to STI571 acquired
      resistance in leukemia treatment.

PMID- 15863198
TI  - Curing acute myelogenous leukemia: still a major challenge.

PMID- 15863199
TI  - High dose intermittent ARA-C (HiDAC) for consolidation of patients with de novo
      AML: a single center experience.
AB  - High dose intermittent ARA-C (2x3 g/m(2) i.v., days 1, 3, 5)=HiDAC was introduced
      as consolidation in AML by the CALGB-group in 1994. We treated 44 de novo AML
      patients in CR with up to four cycles of HiDAC (four cycles: 56.8%; three cycles:
      22.7%; two cycles: 6.8%; one cycle: 13.7%). Median duration of aplasia
      (ANC<0.5x10(9)/l) was 12 days. Neutropenic fever occurred in 38.6% of the
      patients during the first, 52.6% during the second, 45.7% during the third, and
      in 40% during the fourth cycle. Non-hematologic toxicity was tolerable. The
      median overall- and disease-free survival were 19.3 and 11.3 months,
      respectively. The best outcome was seen in patients aged <40 years. These results
      confirm that HiDAC is a safe and effective consolidation in AML.

PMID- 15863200
TI  - Prognostic significance of FLT3 mutations in pediatric non-promyelocytic acute
      myeloid leukemia.
AB  - FLT3 is a receptor tyrosine kinase involved in the survival of hematopoietic stem
      cells, and mutations of FLT3 have been reported to be of prognostic significance.
      This is the first study of FLT3 mutations in pediatric non-promyelocytic AML
      patients that received the same treatment scheme in single institute. FLT3
      internal tandem duplication of the juxtamembrane domain (FLT3/ITD) and a point
      mutation in the tyrosine kinase domain (FLT3/TKD) were analyzed in 61 patients by
      PCR of genomic DNA. The incidence of FLT/ITD and FLT/TKD were 6.6% (4/61) and
      3.3% (2/61), respectively. Patients with FLT3/TKD remain alive after autologous
      stem cell transplantation. The disease-free survival (DFS) of patients with
      FLT3/ITD (0%) was significantly lower than that of the others (52%). FLT3/ITD was
      the sole adverse prognostic factor for DFS by multivariate analysis (RR=5.6).
      Patients with FLT3/ITD relapsed early after complete remission even after
      receiving bone marrow transplantation from a matched related donor with little
      BuCy conditioning. New therapeutic scheme such as stem cell transplantation with
      more intensive conditioning just after complete remission could be applied in
      pediatric non-promyelocytic AML patients with the FLT3/ITD mutation.

PMID- 15863201
TI  - Therapy-related myelodysplastic syndrome in childhood: a retrospective study of
      36 patients in Japan.
AB  - We report here a retrospective analysis of 36 children with therapy-related
      myelodysplastic syndrome (t-MDS) diagnosed between 1990 and 1999 in Japan. Their
      median age was 7.7 years and the median latency period for the development of t
      MDS was 38.5 months. The primary tumors were hematologic in 15 of the cases and
      nonhematologic in 21. Chromosomal abnormalities were detected in 32/34(94%)
      patients: abnormalities of chromosomes 5and/or 7 in 41% and notably, 11q23
      abnormalities in 31%. The prognosis of children with t-MDS was very poor as
      compared to children with primary MDS (5 year survival: 16% versus 54%,
      p<0.0001).

PMID- 15863202
TI  - TEL/AML1 and immunoreceptor gene rearrangements-which comes first?
AB  - TEL/AML1 fusion gene is present in 20-25% of childhood acute lymphoblastic
      leukaemias. In order to unravel at which stage of B-cell precursor development
      the fusion is originated, we analysed frequency and pattern of immunoreceptor
      (immunoglobulin and T-cell receptor) gene rearrangements in 47 TEL/AML1-positive
      and 43 TEL/AML1-negative cases of the same CD10+ immunophenotype. Moreover, we
      compared corresponding immunoreceptor gene rearrangements in 11 cases of TEL/AML1
      positive leukaemia at diagnosis and relapse. More mature immunogenotype of
      TEL/AML1-positive cases and changes in 37% of rearrangements between diagnosis
      and relapse suggest that in most cases the TEL/AML1 fusion is formed during
      immunoreceptor gene rearrangement process.

PMID- 15863203
TI  - Thalidomide treatment reduces apoptosis levels in bone marrow cells from patients
      with myelodysplastic syndromes.
AB  - We treated with thalidomide seven patients with primary MDS and observed
      reduction of the transfusion requirement in three cases and reduction of bone
      marrow blasts in one case. The apoptotic rate of bone marrow cells diminished
      significantly from a mean of 43.8% to a mean of 17.5%, whereas the proliferative
      activity did not change. Plasma TNF-alpha, bFGF, IL-1beta levels decreased
      variably, whereas VEGF levels tended to increase. Matrix metalloproteinases 2 and
      9 expression decreased in bone marrow cells of responders. A reduction of CD4
      cells and an increase of NK cells was observed in the peripheral blood. Thus,
      thalidomide may produce a fairly good hematological improvement in erythroid
      series in MDS, with complex biological mechanisms.

PMID- 15863204
TI  - Adaptive randomized study of idarubicin and cytarabine alone or with interleukin
      11 as induction therapy in patients aged 50 or above with acute myeloid leukemia
      or high-risk myelodysplastic syndromes.
AB  - A higher complete remission (CR) rate was observed in patients with acute myeloid
      leukemia (AML) who, on a prior randomized study of induction therapy, received
      gemtuzumab ozogamicin (GO) plus interleukin-11 (IL-11) rather than GO alone. An
      adaptive randomized phase III study of the addition of IL-11 to idarubicin and
      cytarabine (IA) induction in 100 patients >/=50 years of age with AML or high
      risk myelodysplastic syndrome (MDS) was conducted. Median patient age was 67
      years (range 50-82). Twenty-four of the 45 (53%) patients randomized to IA plus
      IL-11 achieved CR. Eight (33%) subsequently relapsed, 4 (17%) died in CR; median
      time to treatment failure (TTF) was 37 weeks. Twenty-nine of the 55 (53%)
      patients treated without IL-11 achieved CR. Eight (28%) subsequently relapsed, 2
      (7%) died in CR; median TTF was 46 weeks. Median overall survivals were 21 and 59
      weeks for the IA plus IL-11 and IA cohorts, respectively (p=0.271, log rank test;
      0.435, Gehan-Breslow test). Ten episodes of the following grade 3 or 4
      cardiopulmonary toxicities were observed in patients receiving IA plus IL-11, 12
      such episodes in those receiving IA alone: atrial fibrillation, pleural
      effusions, myocardial infarction, bradycardia or hypotension. Two patients in
      each arm experienced grade 3 peripheral edema. There was no significant
      difference in incidence of any grade 3 or 4 adverse event, including
      thrombocytopenia, between treatment arms. There was no significant impact on CR
      rates, TTF, survival, or toxicity of adding an IL-11 regimen to IA induction in
      patients >/=50 years of age with AML.

PMID- 15863205
TI  - Methylation of p15(INK4b) and E-cadherin genes is independently correlated with
      poor prognosis in acute myeloid leukemia.
AB  - Hypermethylation of CpG islands is a common mechanism by which tumor suppressor
      genes are inactivated. The tumor suppressor gene p15(INK4b) is important
      component of cell cycles, whereas E-cadherin gene is often termed a metastasis
      suppressor gene. We have studied the feasibility of detecting tumor-associated
      aberrant p15(INK4b) and E-cadherin methylation in acute myeloid leukemia (AML)
      using methylation-specific PCR. Aberrant methylation of p15(INK4b) was detected
      in 31 of 61 (51%) AML patients. On the other hand, E-cadherin hypermethylation
      was detected in 36 of 61 (56%) AML patients. We have examined the methylation
      pattern of these genes and the prognosis in AML patients using a log-rank test.
      Methylation of p15(INK4b) gene significantly correlated with prognosis
      (p=0.0012), and methylation of E-cadherin gene more significantly correlated with
      prognosis (p=0.0004). When both were methylated, there was even more significant
      unfavorable prognosis compared to either of the methylated genes (p<0.0001). We
      interpret these data to mean that dysfunction of the cell cycle and/or the cell
      cell adhesion molecule plays a role in the pathogenesis of acute myeloid leukemia
      and that analysis of the methylation of p15(INK4b) and E-cadherin genes can
      provide clinically important evidence on which to base treatment.

PMID- 15863206
TI  - Analysis of HFE and TFR2 gene mutations in patients with acute leukemia.
AB  - There are increasing evidences regarding the association between iron overload
      and extra-hepatic malignancies. We studied the prevalence of 12 hereditary
      hemochromatosis (HH) gene mutations (C282Y, V53M, V59M, H63D, H63H, S56C, Q127H,
      E168Q, E168X, W169X and Q283P in the HFE gene and Y250X in the TFR2 gene) and its
      correlation with the iron status in 82 adult patients with acute leukemia (AL);
      48 patients (58.5%) were affected by acute myeloid leukemia (AML) and 34 patients
      (41.5%) by acute lymphoblastic leukemia (ALL); 27 patients (32.9%) had at least
      one HH gene mutation (6 heterozygous for C282Y, 6 homozygous for H63D, 13
      heterozygous for H63D and 2 heterozygous for S56C). Mean serum ferritin levels at
      diagnosis were increased (822.5+/-811.4 microg/L). However, there was no
      difference between patients positive or negative for the HH gene mutations.
      Similarly, we did not observe any statistically significant difference as far as
      iron status between AML and ALL patients. Our study does not support the evidence
      of an association between hemochromatosis gene mutations and iron overload in AL
      patients.

PMID- 15863207
TI  - Irregular nuclear shape of bone marrow plasma cells defines a multiple myeloma
      subgroup related to hypodiploidy and to short survival.
AB  - Morphological changes of plasma cells (PC) are common in multiple myeloma (MM).
      Loss of round or oval nuclear shape has been related to cell malignancy in human,
      and we looked for the occurrence of such morphological change on PC from bone
      marrow (BM) smears in a retrospective series of 169 MM patients at diagnosis.
      Nuclear shape changes of PC differed according to the patients (notch, dumb-bell,
      folded or monocytoid appearance), even in the same patient; all subtypes were
      pooled and defined as PC with irregular nuclear shape (PCIN). A significant
      number of PCIN (>/=5% of all BMPC) was found at diagnosis in 20.7%. Median
      survival was of 22 months for patients with >/=5% PCIN, and 41 months for others
      (p=0.0001). Significant relationship was observed with prognostic parameters
      related intrinsic malignancy of the tumour process but not with beta-2
      microglobulin (b2m). A clear-cut relationship was found also between PCIN and
      hypodiploidy (p=0.0001), but not with deletion of chromosome 13. This study
      emphasises the relationship between PCIN, an easy-to-ascertain marker of
      intrinsic malignancy of the tumour process, and adverse prognosis.

PMID- 15863208
TI  - A morphometric approach for the evaluation of angiogenesis in acute lymphoblastic
      leukemia of childhood.
AB  - Angiogenesis was estimated in childhood acute lymphoblastic leukemia (ALL) by the
      use of a novel morphometric method. This was compared with the widely used one of
      microvessel density (MVD). Bone marrow biopsies were evaluated by immunostaining
      with anti-Factor VIII related antigen (FVIIIRAg). Angiogenesis was calculated as
      volume corrected microvessel density index (VC-MVDI), taking into account the
      bone marrow cellularity. According to our results both MVD and VC-MVDI were
      increased at diagnosis of ALL in comparison with the control group. However the
      VC-MVDI increment was not statistically significant. Therefore, VC-MVDI could be
      more representative of the true increase of angiogenesis, correlating better with
      the outcome of the disease.

PMID- 15863209
TI  - Rituximab therapy of lymphoma is enhanced by orally administered (1-->3),(1-->4)
      D-beta-glucan.
AB  - By activating complement, antitumor monoclonal antibodies coat tumor cells with
      iC3b. beta-glucans, naturally occurring glucose polymers, bind to the lectin
      domain of the leukocyte receptor CR3, prime it for binding to iC3b, and trigger
      cytotoxicity of iC3b-coated tumor cells. We studied the combination of the
      complement-activating antibody rituximab with barley-derived (1-->3),(1-->4)-beta
      D-glucan (BG) against CD-20 positive lymphoma xenografts in SCID mice. Growth of
      established subcutaneous non-Hodgkin's lymphoma (NHL) (Daudi and EBV-derived B
      NHL) or Hodgkin's disease (Hs445 and RPMI6666) was significantly suppressed in
      mice treated with a combination of intravenous rituximab and oral BG, when
      compared to mice treated with rituximab or BG alone. Survival of mice with
      disseminated lymphoma was significantly increased in the combination group as
      compared to other treatment groups. No clinical toxicity was observed. The
      therapeutic efficacy and lack of toxicity of this combination supports further
      investigation into its clinical utility.

PMID- 15863210
TI  - Pycnogenol induces differentiation and apoptosis in human promyeloid leukemia HL
      60 cells.
AB  - Pycnogenol, rich of many phytochemicals of medical value, is a commercialized
      nutrient supplement extracted from the bark of European coastal pine. In this
      study, we investigated the anti-tumor effects of Pycnogenol on HL-60, U937 and
      K562 human leukemia cell lines. We found that Pycnogenol inhibited cell
      proliferation dose- and time-dependently, and the IC(50)s of Pycnogenol on HL-60,
      U937 and K562 cells were 150, 40 and 100 microg/ml, respectively. When HL-60
      cells were incubated with low concentrations of Pycnogenol (50, 100 and 125
      microg/ml) for 24 h, a prominent G0/G1 arrest was observed, followed by gradual
      accumulation of sub-G0/G1 nuclei. At 48 h of treatment, 50-70% of HL-60 cells
      differentiated, as evidenced by morphological changes, NBT reduction, induction
      of NSE activity, and increases of cell surface expression of CD11b. However,
      results from Annexin V/PI staining, DAPI staining and DNA fragmentation assay
      indicated that Pycnogenol induced HL-60, U937 and K562 cell apoptosis at their
      respective IC(50)s after 24 h of treatments. Pretreatment of z-DEVD-fmk, a
      caspase-3 specific inhibitor, not only decreased caspase-3 activity but also
      reduced the percentage of apoptotic cells induced by Pycnogenol. This indicated
      that caspase-3 activation was involved in Pycnogenol induced-apoptosis. In
      conclusion, Pycnogenol induced differentiation and apoptosis in leukemia cells.
      Our data suggest that Pycnogenol could serve as a potent cancer chemopreventive
      or chemotherapeutic agent for human leukemia.

PMID- 15863211
TI  - Engineering 3-alkyltriazenes to block bcr-abl kinase: a novel strategy for the
      therapy of advanced bcr-abl expressing leukemias.
AB  - Recently, within the framework of a new strategy termed "combi-targeting," we
      designed ZRCM5 to contain a 2-phenylaminopyrimidopyridine moiety targeted to bcr
      abl kinase and a triazene tail capable of generating a methyldiazonium species
      upon hydrolysis. The ability of ZRCM5 to block tyrosine kinase activity was
      tested in a short 10 min exposure ELISA involving isolated bcr-abl kinase and
      Western blotting assays. The results showed that: (a) ZRCM5 was hydrolyzed with a
      half-life of 27 min in cell culture media, (b) it blocked bcr-abl
      autophosphorylation in promyeloblastic leukemia K562 cells in a dose-dependent
      manner (IC(50)=14.01 microM) and (c) it induced dose-dependent levels of DNA
      strand breaks. In contrast, temozolomide (TEM), a clinical DNA damaging triazene
      capable of generating, like ZRCM5, a methyldiazonium species, could neither block
      bcr-abl tyrosine kinase activity in isolated enzyme nor in whole cell
      autophosphorylation assays. In cells expressing varied levels of bcr-abl, ZRCM5
      was consistently more potent than TEM. The significant potency of ZRCM5 against
      the leukemia cells was attributed to its ability to simultaneously to block bcr
      abl and related DNA repair activity while inducing significant DNA lesions in bcr
      abl expressing leukemia cells. Further studies are ongoing to increase the
      affinity of ZRCM5 with the purpose of further enhancing its potency in bcr-abl
      expressing cells.

PMID- 15863212
TI  - Acute myeloid leukemia cell lines MOLM-17 and MOLM-18 derived from patient with
      advanced myelodysplastic syndromes.
AB  - The two acute myelomonocytic leukemia sister cell lines MOLM-17 and MOLM-18 and
      the Epstein-Barr-virus positive non-malignant B-lymphoblastoid cell lines (B
      LCLs) B422 and B423 were established from the bone marrow sample of a 60-year-old
      Japanese male in the advanced leukemic phase of refractory anemia with excess of
      blasts, a subtype of myelodysplastic syndromes (MDS). MOLM-17/-18 are
      proliferatively responsive to the growth factors present in the culture
      supernatant of the 5637 cell line. The B-LCLs are constitutively growth factor
      independent. MOLM-17 and B422 were established at eight months after the initial
      diagnosis, while MOLM-18 and B423 were derived from a sample one month later.
      Immunophenotyping of the first leukemia sample revealed a mixed lineage leukemia
      immunophenotype with positivity for terminal deoxynucleotidyl transferase (TdT),
      CD13 and CD19; the second sample revealed solely myeloid characteristics with
      positivity for CD13, CD41 and CD61, whereas TdT was negative. MOLM-17/-18 showed
      immunomarker profiles typical of the myelomonocytic lineage. The karyotype
      analysis of MOLM-17/-18 revealed various non-random numerical and structural
      abnormalities including del(5)(q?), -7, der(11)add(11)(p11.2)add(11)(q23),
      add(17)(p11.2), add(18)(p11.2), -20, -22 as common aberrations. Treatment with
      tumor necrosis factor-alpha induced pronounced cellular differentiation of both
      cell lines into macrophage-like cells. The overall profile of MOLM-17/-18 based
      on their extensive immunological, cytogenetic and functional characterization
      suggests that these cell lines together with the paired B-LCLs B422 and B423 may
      represent scientifically significant in vitro models which could facilitate
      investigations into the pathobiology of MDS.

PMID- 15863213
TI  - Immune evasion strategies of pediatric precursor-B acute lymphoblastic leukemia
      after allogeneic bone marrow transplantation-a case study.
AB  - Bone marrow transplantation (BMT) is the primary curative option for
      refractory/relapsed pediatric acute lymphoblastic leukemia. Although post
      transplantation relapse remains a frequent cause of transplantation failure, the
      mechanisms underlying this are poorly understood. In this study, we compared
      allogeneic T cell stimulation induced by sequentially obtained precursor-B acute
      lymphoblastic leukemia (ALL) samples from a single patient with overt graft
      versus leukemia (GVL) activity. We observed a loss of T cell stimulatory capacity
      by post-transplantation relapse samples and changes in expression of MHC and the
      costimulatory molecule CD137 ligand. This study suggests that escape from immune
      mechanisms after withdrawal of immune suppression is important to ALL
      progression.

PMID- 15863214
TI  - Multiple myeloma presenting initially as a solitary pleural effusion later
      complicated by malignant plasmacytic ascites.
AB  - A pleural effusion is a rare presenting feature of multiple myeloma and can be a
      complication of myelomatous ascites as well. An additional unique feature of our
      case includes the finding of a normal bone marrow at the time of presentation
      despite the aggressive course of the disease. To the best of our knowledge after
      an extensive medical literature review, this case is the first one of multiple
      myeloma presenting with a plasmacytic pleural effusion, a negative bone marrow,
      and a late complication of plasmacytic ascites. Involvement of serous cavities in
      myeloma carries a poor prognosis, and there is currently no standard effective
      treatment regimen.

PMID- 15863215
TI  - Late-onset marrow aplasia due to imatinib in newly diagnosed chronic phase
      chronic myeloid leukaemia.

PMID- 15863216
TI  - All-trans retinoic acid related headache in patients with acute promyelocytic
      leukemia: prophylaxis and treatment with acetazolamide.

PMID- 15863217
TI  - Sequential behavior in the rat: a new model using food-reinforced instrumental
      behavior.
AB  - Sequential behavior, probably reflecting procedural learning, has intensively
      been investigated in humans. This work has mainly been done using so-called
      serial reaction time tasks. In such tasks, subjects have to respond rapidly to
      simple visual stimuli appearing at one of four locations by pressing a
      corresponding response key. Unknown to the subjects, these stimuli can follow a
      specific repeating sequence. Learning of such a sequence is typically inferred
      from faster reaction times to sequence as compared to random blocks of stimuli.
      In contrast to human subjects, the analysis of sequential behavior has received
      considerably less attention in rodents, possibly due to the lack of analogous
      animal models there. In order to establish such a model, a method was developed
      in rats to investigate serial reactions under conditions of random or sequential
      stimulus presentation. Operant testing chambers were used which consisted of four
      nose-poke holes with cue lights. These holes were arranged in a square fashion
      with a pellet receptacle in the center. The task of the rat was to rapidly
      respond to an illuminated hole by poking into it in order to obtain food. The
      stimulus locations varied permanently, and these changes pursued either a random
      or serial order. In three experiments with differing methodological details,
      responding under such conditions was analyzed with sequences consisting of 6, 12
      or 13 positions. Evidence was obtained that rats can improve their performance
      under sequence as compared to random conditions, for example, with respect to the
      percentage of reinforcements obtained, or with respect to reaction times.
      Furthermore, methodological factors, like response requirements, were addressed
      which may critically affect experimental outcome. Together, this new kind of
      instrumental task might be useful to analyze sequential performance in the rat,
      and the brain mechanisms by which it is mediated.

PMID- 15863218
TI  - Cognitive impairment in aged rhesus monkeys associated with monoamine receptors
      in the prefrontal cortex.
AB  - The "frontal aging hypothesis" has been proposed by many researchers suggesting
      that the earliest and most severe age-related changes in the cortex occur in the
      frontal lobes. Two of these changes include decreases in cognitive functions
      mediated by the prefrontal cortex (PFC) and significant decreases in
      norepinephrine (NE) and dopamine (DA). To investigate whether the changes in
      these neurotransmitter systems are directly related to the cognitive decline seen
      in aging we utilized the rhesus monkey as a model of normal human aging. Our goal
      was to determine if age-related changes in cognition is associated with changes
      in norepinephrine and dopamine receptor binding density in the PFC. Eight young
      monkeys between five and ten years of age (six males and two female) and eight
      aged monkeys between 25 and 32 years of age (five males and three females) were
      behaviorally characterized. Subsequently on-the-slide in vitro binding assays
      were used to quantify the alpha-1 adrenergic, alpha-2 adrenergic and DA1
      receptors as well as the NE and DA uptake receptors. Aged animals as a group
      demonstrated significant cognitive impairments and aging produced a significant
      decrease in alpha-1 adrenergic and alpha-2 adrenergic receptor binding in the PFC
      but no significant change in binding for the DA1 receptor or the NE or DA uptake
      receptors. Further analysis revealed a significant relationship between monoamine
      receptor binding and cognitive performance on three tasks: delayed non-matching
      to sample, delayed recognition span test and the conceptual set-shifting task.

PMID- 15863219
TI  - Electrolytic lesions to nucleus accumbens core and shell have dissociable effects
      on conditioning to discrete and contextual cues in aversive and appetitive
      procedures respectively.
AB  - The nucleus accumbens (n. acc.) has been implicated in conditioning to both
      discrete and contextual cues but its precise role is as yet controversial because
      conflicting patterns of effect have been reported. These inconsistencies may
      relate to the extent to which the lesions used encroach on different subfields of
      n. acc. and the use of different task variants. The present study compared the
      effects of selective lesions of shell and core subfields of nucleus accumbens (n.
      acc.) across aversive and appetitive trace conditioning variants. In both
      experiments, an auditory stimulus was contiguous with footshock or food, or
      presented at a trace interval. A continuous flashing light in each case provided
      an experimental background stimulus. Conditioning to the cues provided by the
      experimental chambers was also assessed. Rats with electrolytic lesions to the n.
      acc. shell and core showed different patterns of effect in aversive (Experiment
      1) and appetitive (Experiment 2) variants of this procedure. In Experiment 1, the
      core lesion reduced the difference between trace and contiguously conditioned
      groups, in responding to the discrete noise stimulus. However, neither lesion had
      any detectable effect on contextual conditioning. In Experiment 2, the shell
      lesion clearly increased contextual conditioning, selectively in the trace
      conditioned group, but neither lesion had any detectable effect on discrete cue
      conditioning. Thus, whilst the shell and core lesions produced dissociable
      effects on discrete cue and contextual conditioning, the conclusions to be drawn
      depend on the procedural variant in use.

PMID- 15863220
TI  - Hippocampal theta activity related to elicitation and inhibition of approach
      locomotion.
AB  - This study determined if the hippocampal theta rhythm showed phase relationships
      or changes in amplitude and frequency with the onset of stimuli and locomotion in
      a task in which auditory cues initiated and suppressed approach locomotion. Rats
      with electrodes in the dorsal hippocampus lapped at a milk dipper and were
      presented a tone which predicted the delivery of a food pellet. In some trials
      the pellet cue tone was negated by 60-Hz clicks beginning 0.3 s after onset, and
      no pellet was delivered. A video capture system (20-ms sampling) synchronized to
      the hippocampal recording system (10-ms sampling) was used to determine the onset
      of locomotor approach to the pellet area. The findings failed to support
      proposals that phase-related mechanisms play a role in encoding and retrieval of
      movement-related information. Neither the pellet cue nor the negating cue reset
      the theta rhythm, and they did not produce differential evoked potentials. During
      milk lapping, theta amplitude increased in the 1/2s prior to all pellet cues
      regardless of their locomotor effect. Frequency also rose but only when a non
      negated pellet elicited short-latency locomotion. During locomotor execution,
      theta peak amplitude peaked earlier than theta frequency by approximately one
      period. In general during performance of this task, increasing theta amplitude
      reflected a general preparation to process the cue and increasing theta frequency
      reflected the readiness to respond to the cue with locomotion.

PMID- 15863221
TI  - Locomotor activity and cocaine-seeking behavior during acquisition and
      reinstatement of operant self-administration behavior in rats.
AB  - Recent studies indicate that administration of dopamine D2-like receptor agonists
      reinstates drug-seeking behavior in rodents, whereas dopamine D1-like receptor
      agonists do not. These effects have been related to the ability of these agonists
      to facilitate the expression of sensitized locomotor activity. Presently, we
      describe experiments in which locomotor activity was assessed concomitantly with
      operant performance during acquisition, extinction and reinstatement. We report
      that locomotor activity was inversely related to drug-seeking behavior during
      acquisition of cocaine self-administration under a Fixed Ratio (FR) 1 schedule of
      reinforcement. During a single trial extinction session, animals that had
      acquired cocaine self-administration exhibited a conditioned increase in drug
      seeking behavior, but there was no evidence of a conditioned locomotor response.
      During reinstatement, cocaine (20 mg/kg) significantly increased both locomotor
      activity and drug-seeking behavior. The dopamine D2-like receptor agonist
      quinpirole (0.5 mg/kg) increased drug-seeking behavior, but did not significantly
      increase locomotor activity. In contrast, the dopamine D1-like receptor agonist
      SKF 81297 (0.5 mg/kg) failed to reinstate drug-seeking behavior, but produced
      significant locomotor activation. To determine whether the inability of SKF 81297
      to promote reinstatement is related to the strength of operant conditioning,
      additional rats were trained to self-administer cocaine using an FR-3 schedule of
      reinforcement. Despite achieving response rates during training almost four times
      higher compared to the FR-1 condition, administration of SKF 81297 again failed
      to significantly increase drug-seeking behavior during reinstatement testing.
      These results extend previous findings, confirming the important role of D2-like,
      but not D1-like receptor activation in the reinstatement of drug-seeking
      behavior. An understanding of the mechanisms by which D1- and D2-like agonists
      differentially influence locomotor activation and drug-seeking behavior in
      cocaine-experienced rodents may prove critical to the development of increasingly
      effective pharmacotherapies for substance abuse.

PMID- 15863222
TI  - Behavioral effects of photothrombotic ischemic cortical injury in aged rats
      treated with the sedative-hypnotic GABAergic drug zopiclone.
AB  - Sedative-hypnotic drugs commonly used in the elderly may affect functional
      recovery following cerebrovascular events. Previous research has shown that
      prolonged exposure to diazepam can interfere with recovery of function and
      exaggerate tissue loss after brain injury. The present study evaluated the effect
      of zopiclone, a widely used hypnotic drug, on functional and histological outcome
      after cortical photothrombosis in aged rats, which might be particularly
      vulnerable to brain insults and inhibitory sedative-hypnotic drugs. Aged Wistar
      rats were treated with zopiclone at a dose of 3 mg/kg (i.p., once a day)
      beginning 4 days before ischemia induction and continuing for 23 days.
      Sensorimotor recovery was assessed by a new ledged beam-walking test and spatial
      learning by the Morris water-maze. After a 7-day washout period all rats were
      administered a single dose of zopiclone (3 mg/kg, i.p.) and retested. Infarct
      volumes were measured from nitroblue tetrazolium-stained sections at the end of
      the experiment. Beam-walking data showed that ischemic rats treated with
      zopiclone were not more impaired than untreated rats. Indeed, they showed fewer
      faults with the impaired hindlimb than ischemic controls on post-operative day
      16. Water-maze performance was not affected by zopiclone. After the washout
      period a single dose of zopiclone did not worsen forelimb or hindlimb function,
      but seemed to improve performance in the water-maze test. Cortical infarct
      volumes were similar in ischemic controls and ischemic rats treated with
      zopiclone. In conclusion, zopiclone was not detrimental and even seemed to
      improve behavioral outcome without affecting ischemic damage in aged rats
      subjected to cortical photothrombosis.

PMID- 15863223
TI  - Postural changes after lesions of the substantia nigra pars reticulata in
      hemiparkinsonian monkeys.
AB  - Current neurosurgical strategies target overactive brain regions including the
      subthalamic nucleus, globus pallidus and thalamus to control various symptoms of
      Parkinson's disease. Subthalamotomy improves akinesia and can induce postural
      deficits in both parkinsonian humans and animals, pallidotomy improves limb
      dyskinesia and more variably, distal bradykinesia whilst thalamotomy improves
      tremor. Because the SNr also becomes overactive in PD and there are few surgical
      studies in parkinsonian primates, we therefore evaluated the effects of lesioning
      the SNr in hemiparkinsonian marmosets to establish the effects on symptomatology.
      Nine monkeys received unilateral 6-hydroxydopamine (6-OHDA) lesions. Seven weeks
      later, four received kainic acid lesions of the SNr. Behavioural tests were
      performed prior to 6-OHDA surgery and then fortnightly for 14 weeks. Unilateral 6
      OHDA lesions induced ipsilateral postural bias, ipsilateral rotation after
      amphetamine injection and bradykinesia. Whilst, SNr lesions significantly altered
      the direction of head position and amphetamine-induced rotation relative to 6
      OHDA lesions, there was no improvement in 6-OHDA-induced reaching deficits or
      sensorimotor neglect. Unbiased quantitation of the nigral lesions showed on
      average 88% loss of dopaminergic neurons after 6-OHDA lesions and 77% loss of non
      dopaminergic neurons after SNr lesions. Our results demonstrate that the SNr is
      important in body orientation changes in parkinsonism.

PMID- 15863224
TI  - Opioid receptor function in social attachment in young domestic fowl.
AB  - Opioid systems are implicated in social attachment processes. This research
      sought to determine the functional contribution of each opioid receptor in
      modulating social attachment/separation distress. Following ICV administration of
      opiate probes, 7-day-old cockerels were isolated from conspecifics for a 3 min
      test period under either a mirror or no-mirror condition. Vocalizations served as
      the measure of separation-stress. Opioid receptor probes included: the mu agonist
      DAMGO (0.02, 0.19, 1.95 nmol), the mu antagonist CTOP (0.009, 0.09, 0.9 nmol),
      the delta agonist SNC80 (0.3, 1.0, 3.0 micromol), the delta antagonist
      naltrindole (0.2, 2.2, 22.2 nmol), the kappa agonist U50, 488 (1, 30, 100 nmol),
      the kappa antagonist norBNI (1.3, 13.6, 136.1 nmol), the NOP agonist N/OFQ (0.01,
      0.1, 1.0 nmol), and the NOP antagonist UFP-101 (0.1, 1.0, 10.0 nmol). DAMGO
      attenuated separation distress vocalizations. No other drug probe enhanced or
      attenuated distress vocalizations. Further, the non-selective opiate antagonist
      naloxone (0.3, 8.3, 27.5 nmol) did not exacerbate distress vocalizations. These
      results suggest that only the mu receptor modulates social attachment in young
      domestic fowl.

PMID- 15863225
TI  - Dentate gyrus-selective colchicine lesion and performance in temporal and spatial
      tasks.
AB  - The effects of multiple-site, intradentate, colchicine injections on the
      performance of a temporal, 'differential reinforcement of low rates of
      responding' (DRL-20s) task and a spatial, 'delayed non-matching-to-place' (DNMTP)
      task in a plus-maze were investigated in rats trained in both tasks prior to the
      lesion. Quantitative analysis revealed a greater than 86% reduction in the
      dentate gyrus (DG) of the colchicine-injected rats compared to the sham-operated
      controls. Dentate gyrus damage rendered rats less efficient than sham-operated
      controls in the performance of the DRL-20s task. The DRL inter-response time
      (IRT) distribution for the DG-lesioned rats and the sham-operated controls was
      similar; however, while the distribution peak for the control rats was 20s, it
      was 16s for the DG-lesioned rats, indicating that the latter rats underestimated
      time. Performance of the DG-lesioned rats was also disrupted in the DNMTP task.
      However, DG-lesioned rats recovered control levels of performance during repeated
      training with an intertrial interval equal to 3s. An increase in intertrial
      interval in lesioned and sham-operated controls disrupted performance in both
      groups; however, while DG-lesioned rats performed at chance levels when the
      intertrial interval was increased to 4min or longer, the sham-operated controls
      performed at chance levels only when the intertrial interval was increased to
      16min. These results seem most parsimoniously interpreted following the cognitive
      map theory of hippocampal function.

PMID- 15863226
TI  - Ibotenic acid lesions of the medial prefrontal cortex block the development and
      expression of 3,4-methylenedioxymethamphetamine-induced behavioral sensitization
      in rats.
AB  - There is ample evidence that plastic changes in the nervous system require the
      excitatory amino acid transmission. This appears to be also the case for
      psychostimulant-induced behavioral sensitization. More specifically the
      glutamatergic input from the medial prefrontal cortex (mPFC) to the VTA and the
      NAc appears to be involved in behavioral sensitization processes. However,
      dissociations regarding the role of the mPFC with respect to the development and
      expression of sensitization, as well as with respect to the psychostimulant being
      studied (amphetamine versus cocaine) appear to exist. The present study examined
      the role of the dorsal mPFC in the development and expression of 3,4
      methylenedioxymethamphetamine (MDMA)-induced sensitization. Bilateral ibotenic
      acid or sham lesions of the dorsal mPFC were performed 7 days prior to or 4 days
      after a context-dependent sensitization-inducing regimen of MDMA (15 mg/kg i.p.)
      or saline. Rats were then challenged with MDMA (5 mg/kg i.p.) after 12 days of
      withdrawal. Ibotenic acid lesions did not affect the activating effects of MDMA,
      but prevented the development and expression of MDMA sensitization. Thus, the
      distance traveled during the development phase of sensitization increased in sham
      lesioned rats but not in ibotenic-lesioned animals. Similarly, sham-lesioned rats
      showed a sensitized response when challenged with MDMA after the withdrawal
      period, an effect not observed in ibotenic-lesioned animals. These data reinforce
      the view that the dorsal mPFC is involved in psychostimulant sensitization and
      more specifically they indicate that the dorsal mPFC plays a key role in the
      development and expression of MDMA-induced behavioral sensitization.

PMID- 15863227
TI  - Permanent, 3-stage, 4-vessel occlusion as a model of chronic and progressive
      brain hypoperfusion in rats: a neurohistological and behavioral analysis.
AB  - Permanent, 3-stage, 4-vessel occlusion (4-VO) was evaluated as a practicable
      model of progressive, cerebral hypoperfusion in rats, resulting in quantifiable,
      reproducible, neuronal damage within a time interval shorter than that described
      in the 2-VO model. The effect of permanent and graded 4-VO on cognition was also
      evaluated using the newly developed, aversive radial maze. The vertebral arteries
      (VA) plus the common carotid arteries (CCA) or internal carotid arteries (ICA)
      were progressively and permanently occluded, following different experimental
      sequences (CCA--> VA; VA-->CCA-->CCA or VA-->ICA-->ICA) with inter-stage
      intervals ranging from 1 to 4 weeks. Only two of four groups subjected to 2-stage
      4-VO (CCA-->VA) showed modest reduction in the number of normal-appearing CA1
      pyramidal cells, despite the significant treatment effect (p < 0.001-0.01 versus
      sham). A high rate of mortality (63.8%) was associated with 2-stage 4-VO. More
      pronounced and consistent neuronal damage occurred 8 weeks after 3-stage 4-VO,
      following the sequence VA --> CCA --> CCA (p < 0.001). One month after this
      schedule, profound, persistent cognitive impairment was demonstrated in the
      aversive radial maze (p < 0.01-0.0001). This behavioral effect was not manifested
      when the ICA, rather than the CCA, were occluded, despite the presence of
      significant, although less severe, hippocampal lesioning. The mortality rate was
      significantly reduced when 3-stage 4-VO was used (p < 0.0001). These consistent,
      histological and behavioral effects, combined with a low mortality rate, suggest
      that permanent, 3-stage 4-VO may represent a reliable animal model of chronic,
      progressive, cerebral hypoperfusion.

PMID- 15863228
TI  - Unilateral electrical stimulation of the inferior colliculus of rats modifies the
      prepulse modulation of the startle response (PPI): effects of ketamine and
      diazepam.
AB  - The magnitude of an acoustic startle response can be reduced by a weak stimulus
      presented immediately before the startle-eliciting noise. This phenomenon has
      been termed prepulse inhibition of the startle reaction (PPI). Previous studies
      indicated that the primary neural pathways mediating PPI belong to the brain stem
      and that the inferior colliculus (IC) was crucial. Its destruction reduced PPI.
      Stimulations applied to brain areas may be as deleterious as lesions. Therefore,
      we looked for the possibility of a brain stimulation applied to the IC during a
      PPI test to reduce also PPI. Rats were implanted with chronic electrodes, their
      tips being aimed at the IC. They were located within or close to the inter
      colliculus nucleus. A train of stimulations was applied and PPI was tested
      alternately during and between periods of stimulation. As the most common method
      used to attenuate PPI consists in administrating drugs, for example ketamine, we
      also tested the effect of this drug. Another drug was also tested, diazepam,
      since it alters the functioning of the IC without any known effect on PPI. This
      allowed a comparative analysis of the neurobiological and the pharmacological
      effects. It appeared that the stimulation decreased PPI quantitatively as much as
      ketamine (6 mg/kg) without an effect of the basic startle reaction. These effects
      did not interfere with each other. Diazepam (1 mg/kg) did not modify PPI, neither
      under stimulation nor per se. Only for a very high dose (4 mg/kg), a sedative and
      myo-relaxant one the basic startle and PPI were altered.

PMID- 15863229
TI  - Effect of working memory on evaluation-related frontocentral negativity.
AB  - Recent results suggest that a negative ERP potential emerges not only on error
      trials, but is also found after correct responses. There is broad evidence that
      this component is generated in the anterior cingulate cortex (ACC). The present
      study aimed to explore the influence of working memory demands on the evaluation
      process probably reflected by the negative potential. To this purpose, a modified
      continuous performance task (CPT) was used, with variations of the delay between
      cues and imperative stimuli. Data were analyzed using conventional averaging
      techniques as well as source localization with LORETA (low resolution brain
      electromagnetic tomography). Results suggest a significant effect of working
      memory delay on the amplitude of the post-response negative ERP component. Its
      source was located in the anterior cingulate cortex, with the exact location
      being dependent upon working memory demands. The results support the notion of a
      general response evaluation system reflected by a post-response negative
      component. The findings of a working memory dependent modification of this
      potential suggest a functional link between the medial frontal cortex and the
      lateral frontal regions primarily involved in working memory processing.

PMID- 15863230
TI  - Investigation into the effects of the novel antipsychotic ziprasidone on weight
      gain and reproductive function in female rats.
AB  - Weight gain and sexual dysfunction are serious side effects of certain
      antipsychotic drugs. Ziprasidone, a novel antipsychotic with a unique receptor
      binding profile, is reported to have a low propensity for such side effects.
      Previous results from this laboratory have demonstrated substantial weight gain
      following sub-chronic treatment with olanzapine and risperidone. Risperidone
      induced weight gain and markedly impaired reproductive function while olanzapine
      induced weight gain, without affecting reproductive function. The aim of this
      study was to investigate effects of ziprasidone on weight gain and reproductive
      function in female rats. Ziprasidone (1 and 2.5 mg/kg i.p.) or vehicle was
      administered once daily for 28 days and body weight, food and water intake
      measured, in addition to histological examination of vaginal lavage to determine
      the stage of the oestrous cycle. On day 28, the rats were sacrificed and the
      uterine weights recorded, intra-abdominal fat weight and plasma prolactin levels
      measured. Ziprasidone failed to induce significant weight gain during weeks 1-3,
      however, significant weight gain was observed on day 28 at 2.5 mg/kg (p < 0.05).
      Ziprasidone had no effect on food intake at any time point. A significant
      reduction in water intake (p < 0.05) was observed during the first week of
      treatment with 2.5 mg/kg ziprasidone. Ziprasidone had no effect on intra
      abdominal fat weight, wet or dry uterine weight or plasma prolactin levels. All
      ziprasidone treated animals displayed a normal four-day oestrous cycle. This
      study is the first to report that ziprasidone is without effect on reproductive
      function or ingestive behaviour in the rat.

PMID- 15863231
TI  - Age-progressing cognitive impairments and neuropathology in transgenic CRND8
      mice.
AB  - Patients with Alzheimer's disease suffer from progressive cognitive impairments
      and show distinct post-mortem neuropathology, including beta-amyloid plaques.
      Transgenic (Tg) CRND8 mice carry a mutated human amyloid precursor protein gene
      and show age-related increases in beta-amyloid production and plaque deposition.
      It was previously reported that during the early stages of plaque deposition, Tg
      CRND8 mice demonstrated Morris maze impairments. However, it is unknown if Tg
      mice would be impaired at an earlier age prior to plaque deposition or more
      impaired at a later age with more extensive plaque deposition. In the current
      study, we describe Tg CRND8 age-progressing beta-amyloid neuropathology and
      cognitive abilities in greater detail. At all ages, Tg mice showed normal short
      term memory in the Y-maze. Pre-plaque Tg and age-matched Non-Tg mice did not
      differ in learning the spatial Morris water maze. However, both early and late
      plaque Tg mice showed impairments during acquisition. In addition, although early
      plaque Tg mice performed well in the probe trial, late plaque Tg mice
      demonstrated impaired probe trial performance. Therefore compared to their Non-Tg
      littermates, Tg CRND8 mice demonstrate cognitive impairments that progressed with
      age and seemed to coincide with the onset of beta-amyloid plaque deposition.

PMID- 15863232
TI  - Sleep homeostasis in rats assessed by a long-term intermittent paradoxical sleep
      deprivation protocol.
AB  - Numerous studies have evaluated the sleep homeostasis of rats after short- or
      long-periods of sleep deprivation, but none has assessed the effects of prolonged
      sleep restriction on the rat's sleep pattern. The purpose of the present study,
      therefore, was to evaluate the sleep homeostasis of rats under a protocol of
      chronic sleep restriction. Male Wistar rats were implanted with electrodes for
      EEG and EMG recordings. Using the single platform method, the animals were
      submitted to 18 h of sleep restriction, beginning at 16:00 h (lights on at 07:00
      h), followed by a 6 h sleep window (from 10:00 h to 16:00 h) for 21 days.
      Immediately after this period, rats were allowed to sleep freely for 4 days
      (recovery period). The sleep-wake cycle was recorded throughout the entire
      experiment and the results showed that during the 6h sleep window there was an
      increase on the percentage of sleep time, reflected by augmented time in high
      amplitude slow wave sleep and in paradoxical sleep, when compared to baseline
      sleep, whereas bouts of awakening longer than 1.5 min were greatly reduced, with
      the animals exhibiting a monophasic-type sleep pattern. During the deprivation
      period, paradoxical sleep was abolished. High amplitude slow wave sleep was also
      greatly affected by the protocol. Nonetheless, one day of recovery was sufficient
      to restore the normal sleep pattern. These findings indicate that this protocol
      was capable to induce many changes in the rat's sleep patterns, suggesting that
      during the 6h sleep window there is a sleep adaptive homeostatic process.

PMID- 15863233
TI  - Clozapine attenuates the locomotor sensitisation and the prepulse inhibition
      deficit induced by a repeated oral administration of Catha edulis extract and
      cathinone in rats.
AB  - Locomotor sensitisation and deficits in prepulse inhibition (PPI) induced by
      psychostimulants are two paradigms that have been widely studied as animal
      behavioural models of psychosis. Clozapine is one of the atypical antipsychotic
      agents which has been widely employed to reverse the aforementioned behavioural
      changes in these usual models. In this particular study, locomotor sensitisation
      and prepulse inhibition deficit were induced under the same context by
      intermittent oral administration of S-(-)-cathinone or Catha edulis extract in
      rats. The rats were then challenged by administration of the atypical
      antipsychotic drug, clozapine and were finally challenged with psychostimulants
      after 2-week of withdrawal. Locomotor activity and PPI were assessed and later
      analyses of the neurotransmitter levels were made. The results of this experiment
      show that repeated oral administration of cathinone or C. edulis extract enhanced
      locomotor and exploratory activity and lead to a gradual deficit in prepulse
      inhibition. This locomotor sensitisation and PPI deficit could be reversed by
      administration of clozapine. A challenge with psychostimulant on day 40 (i.e.,
      after 2-week of withdrawal) resulted in a response similar to the initial
      exposure (day 1). Neurotransmitter level analyses showed a significant increase
      in the level of dopamine in the prefrontal cortex (p < 0.05). There was also a
      significant decrease in the level of 5-hydroxytryptamine (5-HT) in the nucleus
      accumbens (p < 0.05) and its metabolite, 5-hydroxyindole acetic acid (5-HIAA) in
      the prefrontal cortex (p < 0.01). In the remaining regions (anterior and
      posterior striatum), there were no significant changes. In conclusion, this is
      the first study to demonstrate that repeated administration of C. edulis extract,
      or commercial cathinone, induces prepulse inhibition deficit and clozapine
      reverses both C. edulis or cathinone-induced sensitised locomotion and prepulse
      inhibition deficit.

PMID- 15863234
TI  - Pharmacological characterization of the ameliorating effect on short-term memory
      impairment and antinociceptive effect of KT-90 in mice.
AB  - (-)-3-Acetyl-6beta-acetylthio-N-cyclopropylmethyl-normorphine (KT-90) is a
      synthesized compound that binds to mu-, delta- and kappa-opioid receptors in
      vitro. KT-90 induces analgesia in the tail-flick test and this effect is
      antagonized by nor-BNI, a selective kappa-opioid receptor antagonist. However,
      lower doses of KT-90 antagonize morphine-induced analgesia. We reported that
      kappa-opioid receptor agonists such as U-50,488H and dynorphin A (1-13), improved
      scopolamine-induced impairment of learning and memory in mice and/or rats. In
      this study, the effects of KT-90 were investigated in an acetic acid-induced
      writhing test and scopolamine-induced memory impairment test using spontaneous
      alternation performance in a Y-maze. Male ddY mice were treated with scopolamine
      (1.65 micromol/kg, s.c.) 30 min before the behavioral test. KT-90 (0.07-2.35
      micromol/kg, s.c.) was injected 30 min before testing. In the writhing test, the
      antinociceptive effect of KT-90 (0.71 micromol/kg) was completely antagonized by
      a selective mu-opioid receptor antagonist, beta-funaltrexamine (10.2 nmol/mouse,
      i.c.v.) and partially antagonized by nor-BNI (4.9 nmol/mouse, i.c.v.), but it was
      not antagonized by a selective delta-opioid receptor antagonist, naltrindole (9.1
      pmol/mouse, i.c.v.). KT-90 significantly improved the impairment of spontaneous
      alternation induced by scopolamine. The ameliorating effect of KT-90 was not
      antagonized by nor-BNI, but was almost completely antagonized by a selective
      sigma receptor antagonist, NE-100 (2.6 micromol/kg, i.p.). These results
      suggested that the KT-90-induced antinociceptive effect was mediated by mu- and
      partially by kappa-opioid receptors, and the KT-90-induced improvement in
      scopolamine-induced impairment of spontaneous alternation was mediated mainly via
      sigma receptors.

PMID- 15863235
TI  - Automated home cage observations as a tool to measure the effects of wheel
      running on cage floor locomotion.
AB  - This paper introduces automated observations in a modular home cage system as a
      tool to measure the effects of wheel running on the time distribution and daily
      organization of cage floor locomotor activity in female C57BL/6 mice. Mice (n =
      16) were placed in the home cage system for 6 consecutive days. Fifty percent of
      the subjects had free access to a running wheel that was integrated in the home
      cage. Overall activity levels in terms of duration of movement were increased by
      wheel running, while time spent inside a sheltering box was decreased. Wheel
      running affected the hourly pattern of movement during the animals' active period
      of the day. Mice without a running wheel, in contrast to mice with a running
      wheel, showed a clear differentiation between novelty-induced and baseline levels
      of locomotion as reflected by a decrease after the first day of introduction to
      the home cage. The results are discussed in the light of the use of running
      wheels as a tool to measure general activity and as an object for environmental
      enrichment. Furthermore, the possibilities of using automated home cage
      observations for e.g. behavioural phenotyping are discussed.

PMID- 15863236
TI  - Transport of L-[14C]cystine and L-[14C]cysteine by subtypes of high affinity
      glutamate transporters over-expressed in HEK cells.
AB  - Transport of L-cystine across the cell membrane is essential for synthesis of the
      major cellular antioxidant, glutathione (gamma-glutamylcysteinylglycine). In this
      study, uptake of L-[14C]cystine by three of the high affinity sodium-dependent
      mammalian glutamate transporters (GLT1, GLAST and EAAC1) individually expressed
      in HEK cells has been determined. All three transporters display saturable uptake
      of L-[14C]cystine with Michaelis affinity (K(m)) constants in the range of 20-110
      microM. L-glutamate and L-homocysteate are potent inhibitors of sodium-dependent
      L-[14C]cystine uptake in HEK(GLAST), HEK(GLT1) and HEK(EAAC1) cells. Reduction of
      L-[14C]cystine to L-[14C]cysteine in the presence of 1mM cysteinylglycine
      increases the uptake rate in HEK(GLT1), HEK(GLAST) and HEK(EAAC1) cells, but only
      a small proportion (<10%) of L-[14C]cysteine uptake in HEK(GLT1) and HEK(GLAST)
      cells occurs by the high affinity glutamate transporters. The majority (>90%) of
      L-[14C]cysteine transport in these cells is mediated by the ASC transport system.
      In HEK(EAAC1) cells, on the other hand, L-[14C]cysteine is transported equally by
      the ASC and EAAC1 transporters. L-homocysteine inhibits L-[14C]cysteine transport
      in both HEK(GLAST) and HEK(GLT1) cells, but not in HEK(EAAC1) cells. It is
      concluded that the quantity of L-[14C]cyst(e)ine taken up by individual high
      affinity sodium-dependent glutamate transporters is determined both by the
      extracellular concentration of amino acids, such as glutamate and homocysteine,
      and by the extracellular redox potential, which will control the oxidation state
      of L-cystine.

PMID- 15863237
TI  - Expression of calpastatin, minopontin, NIPSNAP1, rabaptin-5 and neuronatin in the
      phenylketonuria (PKU) mouse brain: possible role on cognitive defect seen in PKU.
AB  - Phenylketonuria (PKU) is an inborn error of amino acid metabolism. Phenylalanine
      hydroxylase (PAH) deficiency results in accumulation of phenylalanine (Phe) in
      the brain and leads to pathophysiological abnormalities including cognitive
      defect, if Phe diet is not restricted. Neuronatin and 4-nitrophenylphosphatase
      domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) reportedly have
      role in memory. Therefore, gene expression was examined in the brain of mouse
      model for PKU. Microarray expression analysis revealed reduced expression of
      calpastatin, NIPSNAP 1, rabaptin-5 and minopontin genes and overexpression of
      neuronatin gene in the PKU mouse brain. Altered expression of these genes was
      further confirmed by one-step real time RT-PCR analysis. Western blot analysis of
      the mouse brain showed reduced levels of calpastatin and rabaptin-5 and higher
      amount of neuronatin in PKU compared to the wild type. These observations in the
      PKU mouse brain suggest that altered expression of these genes resulting in
      abnormal proteome. These changes in the PKU mouse brain are likely to contribute
      cognitive impairment seen in the PKU mouse, if documented also in patients with
      PKU.

PMID- 15863238
TI  - Study of the oxidative stress in a rat model of chronic brain hypoperfusion.
AB  - A multiple analysis of the cerebral oxidative stress was performed on a
      physiological model of dementia accomplished by three-vessel occlusion in aged
      rats. The forward rate constant of creatine kinase, k(for), was studied by
      saturation transfer (31)P magnetic resonance spectroscopy in adult and aged rat
      brain during chronic hypoperfusion. In addition, free radicals in aging rat brain
      homogenates before and/or after occlusion were investigated by spin-trapping
      electron paramagnetic resonance spectroscopy (EPR). Finally, biochemical
      measurements of oxidative phosphorylation parameters in the above physiological
      model were performed. The significant reduction of k(for) in rat brain compared
      to controls 2 and 10 weeks after occlusion indicates a disorder in brain energy
      metabolism. This result is consistent with the decrease of the coefficient of
      oxidative phosphorylation (ADP:O), and the oxidative phosphorylation rate
      measured in vitro on brain mitochondria. The EPR study showed a significant
      increase of the ascorbyl free radical concentration in this animal model.
      Application of alpha-phenyl-N-tert-butylnitrone (PBN) and 5,5-dimethyl-1
      pyrroline N-oxide (DMPO) spin traps revealed formation of highly reactive
      hydroxyl radical (.OH) trapped in DMSO as the .CH(3) adduct. It was concluded
      that the ascorbate as a major antioxidant in brain seems to be useful in
      monitoring chronic cerebral hypoperfusion.

PMID- 15863239
TI  - Oxidative stress induced by beta-amyloid peptide(1-42) is involved in the altered
      composition of cellular membrane lipids and the decreased expression of nicotinic
      receptors in human SH-SY5Y neuroblastoma cells.
AB  - The neurotoxic effects and influence of beta-amyloid peptide (Abeta)(1-42) on
      membrane lipids and nicotinic acetylcholine receptors (nAChRs) in human SH-SY5Y
      neuroblastoma cells were investigated in parallel. Exposure of the cultured cells
      to varying concentrations of Abeta(1-42) evoked a significantly decrease in
      cellular reduction of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5,diphenyl tetrazolium
      bromide), together with enhanced lipid peroxidation and protein oxidation.
      Significant reductions in the total contents of phospholipid and ubiquinone-10,
      as well as in the levels of the alpha3 and alpha7 subunit proteins of nAChRs were
      detected in cells exposed to Abeta(1-42). In contrast, such treatment had no
      effect on the total cellular content of cholesterol. Among these alterations,
      increased lipid peroxidation and decreased levels of cellular phospholipids were
      most sensitive to Abeta(1-42), occurring at lower concentrations. In addition,
      when SH-SY5Y cells were pretreated with the antioxidant Vitamin E, prior to the
      addition of Abeta(1-42), these alterations in neurotoxicity, oxidative stress,
      composition of membrane lipids and expression of nAChRs were partially prevented.
      These findings suggest that stimulation of lipid peroxidation by Abeta may be
      involved in eliciting the alterations in membrane lipid composition and the
      reduced expression of nAChRs associated with the pathogenesis of AD.

PMID- 15863240
TI  - Dopamine transporters are involved in the onset of hypoxia-induced dopamine
      efflux in striatum as revealed by in vivo microdialysis.
AB  - Although many studies have revealed alterations in neurotransmission during
      ischaemia, few works have been devoted to the neurochemical effects of mild
      hypoxia, a situation encountered during life in altitude or in several
      pathologies. In that context, the present work was undertaken to determine the in
      vivo mechanisms underlying the striatal dopamine efflux induced by mild
      hypoxaemic hypoxia. For that purpose, the extracellular concentrations of
      dopamine and its metabolite 3,4-dihydroxyphenyl acetic acid were simultaneously
      measured using brain microdialysis during acute hypoxic exposure (10% O(2), 1h)
      in awake rats. Hypoxia induced a +80% increase in dopamine. Application of the
      dopamine transporters inhibitor, nomifensine (10 microM), just before the hypoxia
      prevented the rise in dopamine during the early part of hypoxia; in contrast the
      application of nomifensine after the beginning of hypoxia, failed to alter the
      increase in dopamine. Application of the voltage-dependent Na(+) channel blocker
      tetrodotoxin abolished the increase in dopamine, whether administered just before
      or after the beginning of hypoxia. These data show that the neurochemical
      mechanisms of the dopamine efflux may change over the course of the hypoxic
      exposure, dopamine transporters being involved only at the beginning of hypoxia.

PMID- 15863241
TI  - The effects of moderate-, strenuous- and over-training on oxidative stress
      markers, DNA repair, and memory, in rat brain.
AB  - We have tested the hypothesis that training with moderate- (MT), strenuous- (ST),
      or over- (OT) load can cause alterations in memory, lipid peroxidation, protein
      oxidation, DNA damage, activity of 8-oxoG-DNA glycosylase (OGG1) and brain
      derived neurotrophic factor (BDNF), in rat brain. Rat memory was assessed by a
      passive avoidance test and the ST and OT group demonstrated improved memory. The
      content of BDNF was increased only in the OT group. The oxidative damage of
      lipids and DNA, as measured by thiobarbituric acid reactive substances (TBARS),
      and 8-hydroxydeoxyguanosine (8-OHdG), did not change significantly with exercise.
      Similarly, the activity of DNA repair enzyme, 8-oxoguanine DNA glycosylase
      (OGG1), was not altered with exercise training. On the other hand, the content of
      reactive carbonyl derivatives (RCDs) decreased in all groups and the decrease
      reached significance levels in the ST and OT groups. The activity of the
      proteasome complex increased in the brain of OT. The findings of this study imply
      that over-training does not induce oxidative stress in the brain and does not
      cause loss of memory. The improved memory was associated with enhanced BDNF
      content.

PMID- 15863242
TI  - Proteome analysis in hippocampus of mice overexpressing human Cu/Zn-superoxide
      dismutase 1.
AB  - Cu/Zn-superoxide dismutase 1 (SOD1), encoded on chromosome 21, is a key enzyme in
      metabolism of oxygen free radicals and oxidative stress. Transgenic mice
      overexpressing human SOD1 (Tg-hSOD1) are useful model for Down syndrome (trisomy
      21) and familial amyotrophic lateral sclerosis (ALS). It was shown recently that
      Tg-hSOD1 mice develop a characteristic set of neurodegenerative changes in
      hippocampus and we therefore decided to study differential protein expression
      patterns, constructing a mouse hippocampal proteome map using two-dimensional
      electrophoresis (2-DE) with in-gel digestion of spots followed by matrix-assisted
      laser desorption/ionisation-time of flight (MALDI-TOF) identification and
      quantitatively compared protein profiles between non-transgenic mice, hemizygous
      and homozygous Tg-hSOD1 mice. In total 1056 spots were analysed, resulting in the
      identification of 445 polypeptides that were the products of 157 different genes.
      Among these a series of proteins involved in scaffolding, metabolism, signaling
      and other functions were deranged. Our findings suggest that overexpressed SOD1
      directly or by generating reactive oxygen species may lead to aberrant protein
      expressional patterns that in turn may lead to or reflect neurodegeneration
      observed in this animal model.

PMID- 15863243
TI  - The mechanism of manganese-induced inhibition of steroidogenesis in rat primary
      Leydig cells.
AB  - In previous studies in cultured primary rat Leydig cells, manganese was shown to
      inhibit hCG-stimulated steroidogenesis of Leydig cells, and the data showed that
      while the inhibition of StAR protein expression and/or function and mitochondrial
      dysfunction contribute to the acute reduction of steroidogenesis (2 and 4h
      manganese treatment), the enzyme activities of P450scc and 3beta-HSD were only
      reduced after 24h manganese treatment, we hypothesize that there were different
      mechanisms for its effect at later stage (24 and 48 h manganese treatment). We
      further our study by examining StAR mRNA level in cultured primary rat Leydig
      cells to understand if inhibition of StAR protein expression occurs at the level
      of transcription of StAR mRNA. The cellular ATP content was measured to determine
      the extent that manganese altered mitochondrial function. Since mitochondria are
      regulators of Ca(2+) homeostasis, and there are indications that manganese
      affects intracellular Ca(2+) levels, [Ca(2+)]i was also tested. The effects of
      manganese on Leydig cell apoptosis and cell cycle distribution were studied to
      see whether these effects contribute to the reduction of steroidogenesis by
      manganese at later stage of manganese treatment. In the present study, we
      demonstrated that manganese could increase [Ca(2+)]i and reduced ATP contents in
      primary Leydig cells after 4h treatment, while the effects on StAR mRNA level
      appeared later (24h). Manganese could also induce arrest at the G(0)/G(1) phase
      cell cycle after 24h manganese treatment and subsequently increased in the sub
      G(1) phase DNA contents, indicating induction of apoptosis. Combined with our
      previous studies, the results indicate that inhibition of StAR protein expression
      and/or function, mitochondrial dysfunction and disturbance of calcium homeostasis
      contribute to the adverse effects of manganese on the Leydig cells at the
      early/immediate stage after treatment (2 and 4h). However, at later stages (24
      and 48 h) manganese could arrest the cell cycle and induce apoptosis of primary
      Leydig cells, StAR mRNA and enzyme activities of P450scc and 3beta-HSD were also
      reduced, leading to reduced level of steroidogenesis in cultured primary Leydig
      cells.

PMID- 15863244
TI  - Comparison of developmental toxicity of selective and non-selective
      cyclooxygenase-2 inhibitors in CRL:(WI)WUBR Wistar rats--DFU and piroxicam study.
AB  - BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested
      drugs during pregnancy. Unlike general toxicity data, their prenatal toxic
      effects were not extensively studied before. The aim of the experiment was to
      evaluate the developmental toxicity of the non-selective (piroxicam) and
      selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl
      2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once
      daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at
      0.3, 3.0 and 30.0mg/kg for piroxicam and 0.2, 2.0 and 20.0mg/kg for DFU. Fetuses
      were delivered on GD 21 and routinely examined. Comprehensive clinical and
      developmental measurements were done. The pooled statistical analysis for
      ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses
      exposed to piroxicam, selective and non-selective COX-2 inhibitor based on
      present and historic data. RESULTS: Maternal toxicity, intrauterine growth
      retardation, and increase of external and skeletal variations were found in rats
      treated with the highest dose of piroxicam. Decrease of fetal length was the only
      signs of the DFU developmental toxicity observed in pups exposed to the highest
      compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed
      groups. Prenatal exposure to non-selective COX inhibitors increases the risk of
      VSD and MD when compared to historic control but not with selective COX-2
      inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were
      toxic for rats fetuses when administered in the highest dose. Unlike DFU,
      piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2
      inhibitors does not increase the risk of ventricular septal and midline defects
      in rat when compared to non-selective drugs and historic control.

PMID- 15863245
TI  - Effect of cysteine, methionine, ascorbic acid and thiamine on arsenic-induced
      oxidative stress and biochemical alterations in rats.
AB  - Oxidative stress due to enhanced production of free radicals has been
      incriminated as one of the several mechanisms involved in arsenic-induced toxic
      effects in different organs. In the present study, ameliorative potential of
      certain amino acids like cysteine, methionine and vitamins like ascorbic acid and
      thiamine on some of the parameters indicative of oxidative stress in liver,
      kidney and blood and of hepatic and renal infliction was investigated in arsenic
      exposed rats. Rats were given 0 ppm (group I healthy controls) or 10 ppm arsenic
      in drinking water ad lib for a period of 12 weeks. During oral exposure to
      arsenic rats of different groups received daily oral dose of placebo, cysteine,
      methionine, ascorbic acid or thiamine at 25mg/kg body weight. After the end of
      the experimental period, animals were sacrificed under light anesthesia and
      blood, liver and kidney were collected. Samples were processed for estimation of
      arsenic, biochemical parameters indicative of oxidative stress and hepatic and
      renal function. Arsenic exposure resulted in significantly (P<0.05) higher
      accumulation of arsenic in blood, liver and kidney. It was associated with
      significant (P<0.05) rise in lipid peroxide level and decrease in superoxide
      dismutase and catalase activities in liver and kidneys. However, alterations in
      biochemical parameters did not reach statistical (P>0.05) significance. Treatment
      with vitamins and amino acids resulted in reversal of oxidative stress with
      significant (P<0.05) decline in tissue arsenic burden. All the treatment produced
      tissue specific changes in lipid peroxide level, antioxidant enzyme activities
      and tissue arsenic burden.

PMID- 15863246
TI  - Repeated cadmium nebulizations induce pulmonary MMP-2 and MMP-9 production and
      emphysema in rats.
AB  - This study describes induction of pulmonary inflammation, production of matrix
      metalloprotease of type 2 (MMP-2) and type 9 (MMP-9), and emphysema in cadmium
      (Cd)-exposed rats. Sprague-Dawley rats were randomly distributed into two groups:
      one placebo-exposed group undergoing saline (NaCl 0.9%) inhalation (n=30) and one
      Cd-exposed group undergoing cadmium (CdCl(2) 0.1%) inhalation (n=30). The animals
      of the placebo- and Cd-exposed groups were divided in five subgroups (n=6).
      Subgroups underwent either a single exposure of 1h or repeated exposures three
      times weekly for 1h during 3 weeks (3W), 5 weeks (5W), 5 weeks followed by 2
      weeks without exposure (5W+2) or 5 weeks followed by 4 weeks without exposure
      (5W+4). Each animal underwent determination of enhanced pause (Penh) as index of
      airflow limitation prior to the first exposure as well as before sacrifice. The
      animals were sacrificed the day after their last exposure. The left lung was
      fixed for histomorphometric analysis (determination of median interwall distance
      (MIWD)), whilst bronchoalveolar lavage fluid (BALF) was collected from the right
      lung. BALF was analyzed cytologically, and MMP-2 and MMP-9 levels were determined
      by gelatine zymography. Twelve rats previously instilled with pancreatic elastase
      were used as positive emphysema controls and underwent the same investigations.
      Cd-exposure induced a significant increase of BALF macrophages, neutrophils and
      MMP-9 up to 5W+4, whereas MMP-2 gelatinolytic activity returned to baseline
      levels within 5W. MIWD was significantly increased in all repeatedly Cd-exposed
      groups and elastase-treated rats. Penh was increased in Cd-exposed rats after a
      single exposure and after 3W. MMP gelatinolytic activity was significantly
      correlated with macrophages, neutrophils and Penh. In repeatedly exposed rats,
      MIWD was positively and significantly correlated with MMP gelatinolytic activity,
      suggesting that increased MMP-2 and MMP-9 production favours the development of
      emphysema.

PMID- 15863247
TI  - Early behavioral effects of lead perinatal exposure in rat pups.
AB  - Acoustic analysis of infants crying, a sensitive and selective index for
      measuring the effect of pre and perinatal lead exposure, may provide an early
      marker for central nervous system damage produced by the toxic. The present study
      evaluated the effects of exposure to low lead levels during perinatal and early
      postnatal periods on ultrasonic vocalization (USV), an early behavior of rat pups
      essential to their development. Non-sexually experienced females were gavaged
      daily with 8, 16 or 24 mg/kg of lead acetate or the control solution (1 ml/kg)
      for 30 days prior to breeding and until their pups were weaned. After crossover
      of dams, pups had been exposed to lead during pregnancy+lactation, pregnancy or
      lactation. The physiological variables measured on postnatal days 7 or 14 were
      USV, locomotion, rectal temperature, body weight and blood lead levels. Lead
      exposition during pregnancy+lactation, pregnancy or lactation induced a
      significant dose-dependent decrease of USV of 7-day-old pups. On the contrary,
      lead exposition during the different phases of pregnancy induced a significant
      dose-dependent increase of USV in 14-day-old rat pups. Blood lead levels varied
      from 5.7 to 36.5 microg/dl in pups. Body weight and temperature were not
      influenced by lead exposition. Lead-exposed 14-day-old pups were significantly
      more active. This study provides evidence of developmental changes in USV
      emission in rat pups exposed with low lead levels.

PMID- 15863248
TI  - Behavioral effects of adult rats concurrently exposed to high doses of oral
      manganese and restraint stress.
AB  - The behavioral effects of concurrent exposure of high doses of manganese (Mn) and
      restraint stress were assessed in adult rats. Male Sprague-Dawley rats (250-300
      g) received 0, 275 and 550 mg/kg/day of Mn in the drinking water for 19 weeks.
      Each group was divided into two subgroups. Animals in one subgroup were
      restrained for 2h/day. During the treatment period, food and water intake, and
      body weight were weekly recorded. At the end of the treatment period, activity
      levels were monitored in an open-field. Learning was evaluated by a water-maze
      task during five consecutive days. A trial probe was also conducted to assess the
      time spent in the platform quadrant. Body weight and food consumption were
      significantly reduced in the group receiving 550 mg/kg/day of Mn. A two-way
      analysis of variance (ANOVA) revealed an overall effect of Mn on the total
      distance traveled. Differences on spatial learning were observed in the
      acquisition period, in which rats given 550 mg/kg/day of Mn (alone or restrained)
      were impaired in comparison with the control and the restrained only groups. In
      the probe trial, there was an impaired retention in the group treated with Mn at
      550 mg/kg/day. The results of this investigation in the open-field and water maze
      suggest that it would be plausible that restraint stress and a high exposure to
      Mn interact at common neurotransmitter levels but inducing opposite effects.

PMID- 15863249
TI  - Acrylamide tissue distribution and genotoxic effects in a common viral infection
      in mice.
AB  - Acrylamide (AA) has been shown to cause neurotoxic effects in humans and
      neurotoxic, genotoxic, reproductive, and carcinogenic effects in laboratory
      animals. Infection with the human coxsackievirus B3 (CB3) in the murine model
      results in changed uptake and tissue distribution of several environmental
      pollutants, which may result in aggravated disease. In the present study female
      Balb/c mice were infected with CB3, and on day 1 of the infection, dosed orally
      with approximately 50 microg/kg bw of [(14)C]acrylamide ((14)AA) and subsequently
      sacrificed on day 3 of the infection for studies of the distribution of
      radioactivity and genotoxic effects in terms of the frequency of micronucleated
      erythrocytes. Infected mice developed an expected clinical signs of disease. The
      infection decreased the radioactivity by 45% (p<0.05) in the pancreas but
      increased it by 70% (p<0.05) in the blood and more than two-fold in the thymus
      (p<0.01). However, the infection caused no changes in the radioactivity in the
      brain, heart, liver, lungs, spleen, or kidneys. As a response to the infection
      the proportion of young red blood cells (PCE) decreased to about a third
      (p<0.001) of that in the control mice, but no genotoxic effects were observed.
      Thus, the tissue radioactivity after (14)AA administration indicated an infection
      induced change in the metabolism of AA, the exact pathogenic interpretation of
      which warrants further studies.

PMID- 15863250
TI  - Beneficial cardio-renovascular effects of a low-molecular-weight heparin
      derivative on adriamycin-induced glycosaminoglycanuria and tissue lipid
      abnormalities.
AB  - The present work includes a study on the glycosaminoglycanuric condition induced
      by adriamycin (ADR, a chemotherapeutic agent) and the accompanying secondary
      hyperlipidemia, wherein the treatment with a low-molecular-weight heparin
      derivative (LMWH), certoparin, is evaluated for its protective role (if any) on
      these parameters. Two groups of male albino rats of the Wistar strain (140+/-10
      g) received a single intravenous injection of adriamycin (7.5 mg/kg), and one of
      these groups was treated with a low-molecular-weight heparin-derivative
      (Certoparin Sodium, Troparin; 300 microg/day/rat s.c.), commencing on day 8, for
      a week. Urinary total glycosaminoglycans excretion of the untreated ADR-induced
      group was found to increase on the 8th and the 15th days of observation, when
      compared with the controls. The LMWH treatment commencing on day 8 resulted in
      minimising the glycosaminoglycans (GAGs) excretion by day 15 (p<0.001). Plasma,
      cardiac, hepatic and renal lipids (cholesterol, triglycerides and phospholipids)
      showed a sharp increase in the pathologic group, along with a rise in plasma LDL
      and VLDL cholesterol and drop in HDL cholesterol levels, paralleled by abnormal
      activities of the enzymes involved in lipid metabolism. LMWH treated group showed
      a normalised lipid profile and the activities of the lipid-metabolising enzymes
      was close to that of controls. It is concluded herein that adriamycin
      administration resulted in severe nephropathy manifested by increased
      glycosaminoglycanuria and abnormal lipid metabolism, and that LMWH treatment
      afforded substantial protection by restoring glomerular structure and function,
      and normalised the plasma and tissue lipid levels, lipoprotein profile and the
      activities of lipid-metabolising enzymes.

PMID- 15863251
TI  - Differential effects of diallyl disulfide on neuronal cells depend on its
      concentration.
AB  - Diallyl disulfide (DADS) is one of the organosulfur compounds of garlic. The
      effects of DADS on neuronal cells have not clearly been established. We
      investigated its effects on the viability of neuronal cells (N18D3 cells), the
      levels of free radical and membrane lipid peroxidation, and the cell signals,
      such as phosphatidylinositol 3-kinase (PI3K)/Akt and glycogen synthase kinase-3
      (GSK-3). When N18D3 cells were treated with several concentrations of DADS, the
      viability was not affected up to 25 microM, however, decreased at higher than 25
      microM. The levels of free radicals and membrane lipid peroxidation were
      increased in a dose-dependent manner, especially at higher than 25 microM. The
      treatment of N18D3 cells with 25 microM DADS slightly increased the expressions
      of p85a PI3K, phosphorylated Akt and phosphorylated GSK-3, but the treatment with
      100 microM significantly reduced them. To evaluate whether low concentration of
      DADS, up to 25 microM, had protective effect on oxidative stress-injured N18D3
      cells, the viability of N18D3 cells (pretreated with DADS for 2h versus not
      pretreated) was evaluated 24h after their exposure to 100 microM H(2)O(2) for 30
      min. Compared to the cells treated with only 100 microM H(2)O(2), the
      pretreatment with 25 microM DADS increased the viability, and the expressions of
      p85a PI3K, phosphorylated Akt and phosphorylated GSK-3. These results indicate
      that low concentration of DADS has protective effects on N18D3 cells, whereas
      high concentration is rather cytotoxic. Therefore, some specific optimum
      concentration of DADS may be a new potential therapeutic strategy for oxidative
      stress-injury in vitro model of neurodegenerative diseases.

PMID- 15863252
TI  - Dapsone impairs the bile salt-independent fraction of bile flow in rats: Possible
      involvement of its N-hydroxylated metabolite.
AB  - The effects of dapsone (DDS) treatment (30 mg/kg body wt, twice a day, for 4
      days) on biliary secretory function, with special emphasis on bile salt
      independent bile flow (BSIF), were investigated in male and in female Wistar
      rats. Because DDS is metabolized to its N-hydroxylated parent compound only in
      male rats, any gender difference in DDS effect can be causally attributed to this
      metabolite. The two main driving forces for BSIF, the biliary secretion of
      HCO(3)(-) and glutathione species, were assessed. BSIF was decreased by about 20%
      in male but not in female rats after DDS treatment. Basal biliary HCO(3)(-)
      secretion was decreased also by 20% in males. This was associated with a
      diminished (-37%) expression of the HCO(3)(-) canalicular transporter, anion
      exchanger 2 (AE2), detected by western blotting. Biliary output of reduced
      glutathione (GSH) was not modified by DDS irrespective of gender, whereas
      excretion of oxidized glutathione (GSSG) was increased by 830% in males. This
      latter finding confirmed a gender-dependent oxidative stress associated with
      formation of the N-hydroxylated metabolite of DDS. The expression of multidrug
      resistance-associated protein 2 (Mrp2), a putative transporter of glutathione
      species, was decreased by 38% as detected by western blotting, clearly
      dissociating from preserved or increased biliary excretion of GSH and GSSG. In
      conclusion, our results show an impairment of BSIF by DDS mainly due to a
      decreased AE2-mediated biliary excretion of HCO(3)(-), formation of the N
      hydroxylated metabolite of DDS being a likely mediator. The clinical relevance of
      these findings is discussed.

PMID- 15863253
TI  - Use of the local lymph node assay in assessment of immune function.
AB  - The murine local lymph node assay (LLNA) was originally developed as a predictive
      test method for the identification of chemicals with sensitizing potential. In
      this study we demonstrated that an adapted LLNA can also be used as an immune
      function assay by studying the effects of orally administered immunomodulating
      compounds on the T-cell-dependent immune response induced by the contact
      sensitizer 2,4-dinitrochlorobenzene (DNCB). C57Bl/6 mice were treated with the
      immunotoxic compounds cyclosporin A (CsA), bis(tri-n-butyltin)oxide (TBTO) or
      benzo[a]pyrene, (B[a]P). Subsequently, cell proliferation and interferon-gamma
      (IFN-gamma) and interleukin (IL)-4 release were determined in the auricular lymph
      nodes (LNs) after DNCB application on both ears. Immunosuppression induced by
      CsA, TBTO and B[a]P was clearly detectable in this application of the LLNA.
      Cytokine release measurements proved valuable to confirm the results of the cell
      proliferation assay and to obtain an indication of the effect on Th1/Th2 balance.
      We believe to have demonstrated the applicability of an adapted LLNA as an immune
      function assay in the mouse.

PMID- 15863254
TI  - Stability of arsenic metabolites, arsenic triglutathione [As(GS)3] and
      methylarsenic diglutathione [CH3As(GS)2], in rat bile.
AB  - Inorganic arsenicals such as arsenite (iAs(III)) and arsenate (iAs(V)) are well
      known human carcinogens. Arsenic is metabolized by repetitive reduction and
      oxidative methylation, and is excreted mainly in urine as monomethylated
      arsenicals (MMAs) and dimethylated arsenicals (DMAs). Recently, it has been shown
      that iAs(III) administered intravenously or orally is excreted into bile as
      arsenic-glutathione (As-GSH) complexes such as arsenic triglutathione [As(GS)(3)]
      and methylarsenic diglutathione [CH(3)As(GS)(2)]. In order to carry out the
      speciation of As-GSH complexes, it is important to understand their stability.
      The present study was designed to clarify the stability of As-GSH complexes in
      rat bile, and the role of GSH in stabilizing these complexes. Arsenic species
      were separated on an anion-exchange column and were analyzed by high-performance
      liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC
      ICP MS). As(GS)(3) and CH(3)As(GS)(2) were unstable in bile and were hydrolyzed
      to iAs(III) and monomethylarsonous acid (MMA(III)) in the absence of GSH.
      As(GS)(3) appeared to be stable in the presence of 10mM GSH. Exogenously added
      GSH also stabilized CH(3)As(GS)(2) in bile at the concentrations of 5mM or
      higher. It has been suggested that trivalent arsenicals, especially MMA(III), are
      more toxic than corresponding pentavalent ones. These results suggest that GSH
      plays an important role in preventing hydrolysis of As-GSH complexes and the
      generation of well-known toxic trivalent arsenicals.

PMID- 15863255
TI  - Vitamins deficiency in developing chick during chromium intoxication and
      protection thereof.
AB  - Deficiency of various vitamins in postnatally developing chick during chromium
      intoxication and their recovery during vitamins (B and E) and glutathione
      therapies has been investigated. Study was concentrated on liver, kidney, muscles
      and serum. Newly hatched chicks were reared in laboratory. They were treated with
      a daily dose of 10mg/kg/day potassium dichromate from 2nd to 8th day of their
      age. Thereafter, one group was sacrificed on 9th day. Second group was kept
      without intoxication for another 7 days and sacrificed on 16th day. Three groups
      of chromium pretoxicated animals were exposed to therapeutic agents like vitamins
      (B and E) and glutathione for another 7 days. These animals were sacrificed on
      16th day of their age along with control. Study showed chromium intoxication
      decreases vitamins (B(1), B(2), B(6) and E) in all the tissues and serum. The
      maximum decrease was recorded in serum. The 7 days pretoxicated animals kept
      without any treatment for 7 days revealed a slow increase of vitamins with few
      exceptions. Nevertheless, the recovery of vitamins was quick and significant
      during vitamins and glutathione therapy and in some cases control level was
      achieved.

PMID- 15863256
TI  - o-Aminoazotoluene does induce the enzymes of its own mutagenic activation in
      mouse liver.
AB  - The objective of this study was to investigate the CYP1A1 and CYP1A2 mRNAs and
      enzyme activities in mouse liver during induction with o-aminoazotoluene (OAT) as
      well as the capability of the hepatic S9-fraction from OAT-treated mice to induce
      its own activation to mutagens in the Ames test using S. typhymurium strain TA98.
      The data obtained indicate that when used at appropriate doses, OAT is a PAH-type
      inducer of mouse hepatic microsomal monooxygenases, which activity is not less
      than that of the known inducer 3,4-benzo[alpha]pyrene. In the absence of S9
      fraction enzymes no OAT-mediated mutagenicity was observed in the Ames test. In
      the presence of the S9-fraction from OAT-pretreated mice, OAT induced as high
      revertant numbers, as it did in the presence of the S9 fraction from the liver of
      Aroclor 1254-treated mice. Thus, OAT does induce the enzymes of its own mutagenic
      activation in mouse liver.

PMID- 15863257
TI  - Perfluorooctanoate: Placental and lactational transport pharmacokinetics in rats.
AB  - This study was conducted to develop a quantitative understanding of the potential
      for gestational and lactational transfer of perfluorooctanoate (PFOA) in the rat.
      Time-mated female rats were dosed by oral gavage once daily at concentrations of
      3, 10, or 30 mg/kg/day of the ammonium salt of PFOA (APFO) starting on gestation
      (G) day 4 and continuing until sacrifice. On days 10, 15, and 21G, five rats per
      dose level were sacrificed and blood samples were collected 2h post-dose. Embryos
      were collected on day 10G, amniotic fluid, placentas, and embryos/fetuses were
      collected on days 15 and 21G, and fetal blood samples were collected on day 21G.
      Five rats per dose level were allowed to deliver and nurse their litters, and on
      days 3, 7, 14, and 21 post-partum (PP) milk and blood samples of maternal and pup
      were collected 2h post-dose. All samples were analyzed by high-performance liquid
      chromatography-mass spectrometry (HPLC-MS) for PFOA concentration. Concentrations
      of PFOA in maternal plasma and milk attained steady state during the sampling
      interval. The steady-state concentrations in maternal plasma were 10-15, 25-30,
      and 60-75 microg/mL in rats receiving 3, 10, and 30 mg/kg, respectively. Steady
      state concentrations in milk were approximately 10 times less than those in
      maternal plasma. The concentration of PFOA in fetal plasma on day 21G was
      approximately half the steady-state concentration in maternal plasma. The milk
      concentrations appeared to be generally comparable to the concentrations in pup
      plasma. Pup plasma concentrations decreased from day 3PP to day 7PP, and were
      similar on days 7, 14, and 21PP at all dose levels. PFOA was detected in placenta
      (days 15 and 21G), amniotic fluid (days 15 and 21G), embryo (days 10 and 15G),
      and fetus (day 21G). These pharmacokinetics allow estimation of the dose to
      developing and nursing rat offspring following maternal exposure.

PMID- 15863258
TI  - Functional changes of nicotinic acetylcholine receptor in muscle and lymphocyte
      of myasthenic rats following acute dimethoate poisoning.
AB  - The mechanism underlying intermediate myasthenia syndrome (IMS) following acute
      organophosphate poisoning remains largely unknown. Previous studies indicated
      that the mechanism of myasthenia in rats and IMS patients is most likely due to a
      postsynaptic neurotransmission blocking at neuromuscular junctions (NMJ).
      Nicotinic acetylcholine receptor (nAChR) is a key postsynaptic component at NMJ.
      Whether functional changes of nAChR are related to the development of myasthenia
      has not been demonstrated and addressed in vivo so far. In this study, we
      attempted to investigate temporal and spatial changes of nAChR in the blood
      lymphocyte, muscle and brain of rats during the course of myasthenia after acute
      dimethoate poisoning by using radioligand-binding assay. We found that specific
      nAChR binding activity in the gastrocnemius muscle and blood lymphocytes of
      myasthenia rats was significantly increased at 48h after dimethoate poisoning.
      However, no changes of nAChR binding activity were found in the lymphocytes and
      muscle of non-myasthenia rats which were sacrificed at 1h after intoxication.
      Interestingly, no changes of nAChR and muscarinic acetylcholine receptor (mAChR)
      binding activity were found in the cerebrum and cerebellum of all rats after
      dimethoate intoxication either at 1 or 48h. The change of nAChR specific binding
      activity in the lymphocytes is parallel with that in the skeletal muscle during
      the development of myasthenia. This implied that the changes of nAChR receptor
      binding activity in the skeletal muscle and lymphocytes are highly associated
      with the development of myasthenia. The functional changes of nAChR at NMJ might
      play an important role in the paralysis of skeletal muscle following acute
      organophosphates (OPs) poisoning.

PMID- 15863259
TI  - The effects of 3-methylcholanthrene on lymphocyte proliferation in the common
      carp (Cyprinus carpio L.).
AB  - The sensitivity of lymphocyte proliferation as bioindicator of pollution stress
      was evaluated in the common carp (Cyrinus carpio L.). The time course response of
      peripheral blood leukocyte proliferation in response or not to mitogens was
      measured from 1 to 7 days after peritoneal injection of 3-methylcholantrene (3
      MC), and compared to the time course response of a highly sensitive biomarker,
      induction of cytochrome P450. 3-Methylcholanthrene (40 mg kg(-1)) inhibited both
      B- and T-lymphocyte proliferation in response to lipopolysaccharide (LPS) and
      concanavalin A (Con A). Studies with alpha-naphtofiavone, suggest the lack of
      metabolic processes. 3-Methylcholanthrene alone strongly stimulated resting
      peripheral blood leukocytes (PBLs) proliferation. This effect was not transient.
      The induction of lymphocyte proliferation paralleled the increase in cytochrome
      P450 content in the liver. The specificity of polycyclic aromatic hydrocarbon
      (PAH)-induced lymphocyte proliferation suggests that this immune activity may be
      an early marker of exposure to PAHs in aquatic environments. The capacity of 3-MC
      to induce rapid lymphocyte proliferation may be related to PAH-induced rapid
      clonal expansion in mammals. These results strongly suggested that the underlying
      mechanism might be the same in both models. More studies are needed in fish to
      explain this phenomenon and may be helpful in understanding the occurrence of
      neoplastic epizootics in fish associated with PAH exposition.

PMID- 15863260
TI  - Quantitative comparison of the results obtained by the multiple-dose guinea pig
      maximization test and the non-radioactive murine local lymph-node assay for
      various biocides.
AB  - We compared the results of the multiple-dose guinea pig maximization test (GPMT)
      and the non-radioactive murine local lymph-node assay (LLNA) for various
      biocides. Thirteen out of 17 positive biocides in the GPMT gave positive results
      in the LLNA. In the GPMT, the minimum first induction doses ranged over four
      orders (0.00005-0.5%), while elicitation-threshold doses, which were evaluated
      using an optimally sensitized group of animals in the multiple-dose studies,
      ranged over five orders (0.00006-2.8%). In the LLNA, minimum induction doses
      ranged over more than three orders (0.01-30%). With respect to 13 biocides that
      were positive in both the GPMT and the LLNA, results were quantitatively
      compared. When compared after conversion to corresponding area doses (microg/cm),
      the minimum doses required to elicit skin reaction in guinea pigs were always
      lower than that for induction in mice with all biocides. Correlation between
      minimum induction doses from the GPMT and the LLNA seemed poor (r=0.57), while
      that between minimum induction doses in the LLNA and elicitation-threshold doses
      in the GPMT was relatively good (r=0.73). The results suggest the possibility to
      estimate human elicitation-threshold doses, which are definitely lacking in the
      process of risk assessment for skin-sensitizers, from the data of the LLNA.

PMID- 15863261
TI  - Endothelins in breast tumour cell invasion.
AB  - Endothelins are a family of small, structurally related, vasoactive peptides that
      have a great number of physiological roles in many tissues. The 'endothelin axis'
      consists of three 21 amino acid peptides (ET-1, ET-2 and ET-3), two G-protein
      coupled receptors (ET-RA and ET-RB), and two activating peptidases or endothelin
      converting enzymes (ECE-1 and ECE-2). There is increased expression of the
      endothelin axis in invasive breast cancer compared to the normal breast or non
      invasive neoplastic tissue. Endothelin expression is associated with invading
      regions of tumours in patient biopsies and is more common in tumours with high
      histological grade and lymphovascular invasion, and there is increased systemic
      endothelin in patients with lymph node metastases compared to those without lymph
      node involvement. Stimulation of breast tumour cell lines with endothelins leads
      to an invasive phenotype in vitro. Over-expression of the endothelins and their
      receptors is insufficient to induce an invasive phenotype in benign cells, yet
      expression by tumour cells leads to markedly increased invasive ability
      indicating that endothelins act in concert with other factors--both autocrine and
      paracrine--including cytokines, matrix metalloproteinases and the activation of
      tumour-associated macrophages. The association between endothelins, poor
      prognosis and invasion may mean that the endothelin axis is a valid therapeutic
      target for the treatment of invasive breast cancer. This review summarises our
      current knowledge of endothelins in breast cancer invasion and discusses the
      potential further directions of such research as well as the possibility of anti
      endothelin-based therapy of breast cancer.

PMID- 15863262
TI  - Prevalence of human papillomavirus DNA sequences in verrucous carcinoma of the
      lip: genomic and therapeutic approaches.
AB  - We examined the presence of human papillomavirus (HPV) DNA sequences in tissues
      of verrucous carcinoma (VC) of the lip. Detection and typing of HPV DNA was
      performed using polymerase chain reaction with sequence analysis and restriction
      fragment length polymorphism analysis. All tissues of VC contained HPV DNA and
      one of recurrent case was infected with four different HPV DNAs including high
      risk types. Seven different HPV types were detected in VC, of which (accession
      no. in EMBL/GeneBank/DDBJ databases) has been described as a partial sequences
      from an unknown HPV type. Sequence analysis showed that HPVX is related to HPV-20
      (74.8% sequence homology). These results indicate that various mucosal and
      cutaneous HPVs of high risk types are associated with the one of pathogenesis of
      VC of the lip. In addition, the relationship between VC of the lip and HPV
      infection is discussed, as is therapy against VC.

PMID- 15863263
TI  - Lack of significant modifying effect of arctiin on prostate carcinogenesis in
      probasin/SV40 T antigen transgenic rats.
AB  - Arctiin, a plant lignan that can be extracted from the Arctium lappa (burdock)
      seeds, is a possible environmental endocrine disruptor compounds and have been
      shown to influence sex hormone metabolism as well as protein synthesis, steroid
      biosynthesis. Modifying effects of arctiin on prostate carcinogenesis in
      probasin/SV 40 T antigen (Tag) transgenic (TG) rats were examined. A total of 64
      male TG rats, 6 weeks old, were randomly divided to three experimental groups
      (soybean free Oriental MF diet with 0.1, 0.02, or 0.004% arctiin) and a control
      group (soybean free Oriental MF diet). Animals were killed at the end of week 18.
      Histopathological evaluation of prostate revealed that all the rats in any group
      developed adenocarcinoma in dorsolateral lobe of prostate, except two rats in
      0.1% arctiin treated and one rat in 0.002% arctiin treated groups without
      prostate adenocarcinoma development. However, there were no definite treatment
      related changes with statistical significance in all parameters for prostate
      carcinomas measured in this experiment. These results indicated that arctiin
      might not exert significant modifying effect on prostate carcinogenesis in SV 40
      Tag TG rats at least under the present experiment.

PMID- 15863264
TI  - Retinoids suppress premalignant MCF10AT but not malignant MCF10CA1a breast
      epithelial cells in vivo. Role of retinoic acid receptor beta2 expression.
AB  - Recently we found that retinoic acid receptors (alpha, beta, gamma) and retinoid
      X receptors (alpha, beta, gamma) are variably expressed in MCF10A model of breast
      cancer development and progression. Here we employed this model to assess both in
      vitro and in vivo sensitivity of cells to retinoids and the role of RARbeta2 in
      mediating the antitumor potential of retinoids. In vitro, we found that
      transformation of the benign MCF10A cells into premalignant MCF10AT and malignant
      MCF10CA1a cells increased their sensitivity to 4-(Hydroxyphenyl)retinamide (4
      HPR) and all-trans-retinoic acid (atRA) but not to 9-cis-retinoic acid (9cRA) and
      LGD1069 and this was associated with loss of induction of RARbeta2 by retinoids.
      RARbeta2 expression in premalignant MCF10AT cells decreased their proliferating
      activity and increased their sensitivity to atRA. In vivo, when transplanted into
      the mammary fat pads of nude mice, MCF10A cells did not grow, MCF10AT cells
      formed slow-growing tumor nodules, and MCF10CA1a cells were highly malignant,
      grew quickly and infiltrated the surrounding tissues. Of the retinoids used, only
      4-HPR suppressed the growth of slow-growing hyperplastic and premalignant MCF10AT
      but not of the malignant MCF10CA1a tumor nodules. These data may have clinical
      implication in selecting women with hyperplastic and premalignant breast lesions
      that may benefit the most from clinical trials with retinoids.

PMID- 15863265
TI  - Paclitaxel/Taxol sensitivity in human renal cell carcinoma is not determined by
      the p53 status.
AB  - In this study, we analyzed the role of the p53 status for paclitaxel/Taxol
      sensitivity in renal cell carcinomas (RCCs) of the clear cell type. Using
      immunohistochemistry, nuclear p53 accumulation could not be correlated to the
      paclitaxel/Taxol sensitivity. DNA sequencing detected a p53 gene mutation in two
      out of eight RCC cell lines, i.e. in exon 8 (cell line clearCa-6), and in exon 9
      (cell line clearCa-5). No correlation, however, was found between the p53 status
      of our RCC cell lines and their paclitaxel/Taxol sensitivity as indicated by the
      IC50 values. However, paclitaxel-induced growth inhibition in paclitaxel
      sensitive RCC cell lines was accompanied by an increase in apoptosis,
      irrespective of their p53 status. Although CD95 up-regulation was observed in
      renal cell carcinoma with wild-type p53 upon paclitaxel treatment, paclitaxel
      induced apoptosis itself is triggered independently from the CD95 system. In
      conclusion, the p53 status cannot predict paclitaxel/Taxol sensitivity in RCC
      cell lines of the clear cell type.

PMID- 15863266
TI  - Modulation of response to radiation of human lung cancer cells following insulin
      like growth factor 1 receptor inactivation.
AB  - Targeted disruption of the insulin-like growth factor 1 receptor (IGF-1R)
      restricts proliferation of tumor cells and enhances their in vitro
      radiosensitivity. However, there is little information regarding the effect of
      IGF-1R expression and function on the lung cancer response to radiotherapy. In
      this study, we evaluated the cell surface expression of IGF-1R and the
      antitumoral effect of IGF-1R blockade in combination with irradiation in 6 non
      small cell lung cancer (NSCLC) cell lines. All cell lines showed specific IGF-1
      binding with an affinity ranging from 0.95x10(-9) to 2.3x10(-9) M, which was
      evaluated by competitive binding assay. The amount of binding sites ranged from
      118 to 377 fmol/mg protein. In one cell line (U1810), the combined treatment led
      to synergistic cell death and was associated with an accumulation of cells in the
      G2 phase. IGF-1R activation was able to obstruct serum starvation/radiation
      induced cell death in U1810 cell line. Additive interactions were found for four
      cell lines (A549, H157, H23 and H125) whereas only subadditive effects were
      observed in U1752 cell line. Our results indicate that the IGF-1R is present on
      NSCLC cells and thereby its involvement in the modulation of radiosensitivity in
      lung cancer cells.

PMID- 15863267
TI  - Anti-proliferative activity of Bupleurum scrozonerifolium in A549 human lung
      cancer cells in vitro and in vivo.
AB  - Nan-Chai-Hu, the root of Bupleurum scorzonerifolium, is a traditional Chinese
      herb used in treatment of liver diseases such as hepatitis and cirrhosis. We
      recently reported that the acetone extract of B. scorzonerifolium (BS-AE) could
      inhibit proliferation and induce apoptosis in A549 human lung cancer cells. We
      further examined its anti-proliferative mechanisms and in vivo anticancer effect.
      Our results showed that BS-AE had the ability to cause cell cycle arrest in G2/M
      phase, inducing tubulin polymerization, and activating caspase-3 and -9 in A549
      cells. BS-AE-induced apoptosis could be blocked by the broad caspase inhibitor z
      VAD-fmk in majority. The result of in vivo study showed that BS-AE could suppress
      growth in A549 subcutaneous xenograft tumors. These results indicate that BS-AE
      exerts antiproliferative effects on A549 cells in vitro and in vivo, and prompted
      us to further evaluate and elucidate the chemical composition profile of BS-AE.

PMID- 15863268
TI  - High frequency of frameshift mutation on p53 gene in Taiwanese with non small
      cell lung cancer.
AB  - Extensive researches have found that the mutation of p53 tumor suppressor gene is
      the most frequent event in many human cancers and associated with a poor clinical
      outcome in lung cancer patients. Because the p53 molecular mutation involved in
      tumorigenesis of patients with lung cancer in Taiwan remains poorly defined, the
      aim of this study was to assess the p53 mutation spectrum and possible
      etiological factors of Taiwan's patients with Non-Small Cell Lung Cancer (NSCLC).
      Cancer specimens were obtained surgically from 61 patients with pathologically
      proven NSCLC. Polymerase chain reaction-single strand conformation polymorphism
      (PCR-SSCP) and direct sequencing were used to study p53 mutations in exon 4-8. We
      also performed immunohistochemistry (IHC) to detect p53 protein expression. Our
      results provided that 34 mutations of p53 gene were found in 27 cases with a
      mutation rate of 44% (27/61). There were six cases having more than two p53
      mutations. Among the 34 mutations, 19 were point mutations (56%, 19/34) consisted
      of a majority of missense mutations including transversion (13/19, 68%) and
      transitions (6/19, 32%) with four cases (4/6, 67%) occurring in the CpG sequence.
      One of the most important finding in our study was the high frequency of
      frameshift (44%, 15/34) which included 11 insertions and 4 deletions of p53 in
      NSCLC in Taiwan. Surprisingly, our results disclosed distinct novel mutations at
      codon 181, 185, 208 (Exon 5-6) of p53. Especially, 4 cases with mutation at
      codon181 and codon 185 seemed to have more advanced clinical outcome with
      survival time less than 6 months. In addition, there were two recurring mutations
      at codon 168 and three at condon193. The different mutation spectrum in our
      series, including a high frequency of frameshift mutations and distinctly novel
      hot spots suggested the heterogenous entity of exogenous mutagens in NSCLC in
      Taiwan.

PMID- 15863269
TI  - The XPC poly-AT polymorphism in non-melanoma skin cancer.
AB  - Signature UV-DNA lesions, cyclobutane dimers and 6-4 photoproducts, are repaired
      via the nucleotide excision repair pathway. NER may be subdivided into
      transcription-coupled repair and global genome repair, and the XPC protein is
      specific to this latter repair pathway recognizing helix distorting lesions and
      initiating their repair. Inactivating XPC mutations are associated with xeroderma
      pigmentosa and an extremely high risk of skin cancer. A common polymorphism in
      intron 9 of the XPC gene has been associated with both reduced repair of UV-DNA
      damage (using the host-cell reactivation assay) and increased risk of squamous
      cell head and neck cancer. Here, we have tested the hypothesis that the XPC PAT+
      polymorphism is associated with non-melanoma skin cancer using a population-based
      case control study of skin cancer in New Hampshire (n=1917). Overall, there was a
      modest decreased risk of squamous cell carcinoma (SCC) among those with the
      homozygous variant PAT+/+ genotype (OR 0.8, 95% CI 0.5-1.1) that was most evident
      among tanners (OR 0.4, 95% CI 0.1-1.1), however, these trends failed to reach
      statistical significance. There was no association of the PAT+/+ genotype and
      basal cell carcinoma (OR 1.0, 95% CO 0.7-1.3), however there was a modest, non
      statistically significant, decreased risk among those with the heterozygous
      genotype (OR 0.8, 95% CI 0.7-1.1). We did not detect gene environment
      interactions for either SCC or BCC between the XPC PAT genotype and average hours
      of UV exposure per week, painful sunburn history, nor ionizing radiation therapy.
      These results suggest that the XPC PAT+polymorphism does not play a major role in
      non-melanoma skin cancer, but that it may slightly modify the risk of SCC among
      individuals with a phenotype which results in low UV-DNA adduct burdens. These
      results require further confirmation.

PMID- 15863270
TI  - The missense mutations in the candidate prostate cancer gene ELAC2 do not alter
      enzymatic properties of its product.
AB  - The candidate prostate cancer gene ELAC2 encodes tRNA 3' processing
      endoribonuclease (tRNase ZL). We produced recombinant human tRNase ZL's, which
      contain one to three amino-acid substitutions from three missense mutations
      (Ser217Leu, Ala541Thr, and Arg781His) that are associated with the occurrence of
      prostate cancer. These enzymes were examined for the pre-tRNA cleavage and the
      RNase 65 activity. We did not observe any differences in enzymatic properties
      such as Km and k(cat) values between the wild-type tRNase ZL and its variants. We
      conclude that there is no causality between the enzymatic properties of tRNase ZL
      and the prostate cancer.

PMID- 15863271
TI  - Differences in cell proliferation in rodent and human hepatic derived cell lines
      exposed to ciprofibrate.
AB  - Humans appear to be refractory to some effects of peroxisome proliferators
      including alterations in cell proliferation, whereas rodents are susceptible. In
      this study, differences between the human and rat response to peroxisome
      proliferators were evaluated using rat and human tumour liver cell lines. Rat
      7777 cells were more responsive than human HepG2 cells to ciprofibrate as they
      exhibited a higher decrease in cell number than HepG2, and underwent apoptosis.
      Results from these studies reveal a surprising response in tumour cell lines as
      the typical in vivo response of increased cell proliferation and reduced
      apoptosis was not observed in rat tumour cell lines at concentrations greater
      than those used to elicit the former response.

PMID- 15863272
TI  - The novel phospholipase C activator, m-3M3FBS, induces monocytic leukemia cell
      apoptosis.
AB  - We investigated the effect of the novel phospholipase C activator, m-3M3FBS, on
      the apoptosis of leukemic cells. m-3M3FBS inhibited the growth of the leukemic
      cell lines U937 and THP-1, but not primary monocytes. m-3M3FBS induced the
      apoptosis of U937 cells, which was accompanied by chromatin condensation and DNA
      fragmentation. Moreover, m-3M3FBS-induced apoptosis appeared to involve the down
      regulation of anti-apoptotic Bcl-2, the up-regulation of pro-apoptotic Bax, the
      release of cytochrome c, and caspase activation. m-3M3FBS-induced apoptosis of
      U937 cells was also partly inhibited by BAPTA-AM and EGTA, indicating the
      involvement of intracellular calcium signaling on the apoptosis in U937 cells.
      The results of our study suggest that m-3M3FBS can be developed as a novel anti
      leukemic agent.

PMID- 15863273
TI  - Amino acid transport system L is differently expressed in human normal oral
      keratinocytes and human oral cancer cells.
AB  - Previously, we reported the expression and function of system L amino acid
      transporter in KB human oral epidermoid carcinoma cells. In the present study,
      therefore, we investigated the expression and function of system L amino acid
      transporter in human normal oral keratinocytes (HNOK) and compared the
      expressions and functions of system L amino acid transporters in HNOK and KB
      cells. The HNOK expressed L-type amino acid transporter 1 (LAT1) and L-type amino
      acid transporter 2 (LAT2) with their subunit 4F2hc in the plasma membrane but the
      expression of LAT1 was very weak, which is in contrast to the KB cells expressing
      LAT1 but not LAT2 with the 4F2hc in the plasma membrane. The [14C] L-leucine
      uptake by HNOK, as well as KB cells, was inhibited by the system L selective
      inhibitor BCH. The majority of [14C] L-leucine uptake was, therefore, mainly
      mediated by LAT2 in the HNOK and by LAT1 in the KB cells. These results suggest
      that the transport of neutral amino acids including several essential amino acids
      into the HNOK and KB cells are mainly mediated by LAT2 and LAT1, respectively.
      The specific inhibition of LAT1 in oral cancer cells could be a new rationale for
      anti-cancer therapy.

PMID- 15863274
TI  - p16 gene methylation lacks correlation with angiogenesis and prognosis in
      multiple myeloma.
AB  - Methylation of p16 gene is a relatively frequent molecular finding in multiple
      myeloma (MM), but its clinical implication is disputable. Cell cycle regulators
      are now recognized as active in the control of angiogenesis, which is an integral
      component of pathogenesis and a target for new treatment modalities of this
      disease. On such background, we focused on determining whether loss of p16
      function by methylation could be associated with increased angiogenesis and VEGF
      expression, and the prognostic relevance of p16 methylation in 50 untreated,
      newly diagnosed MM patients. Thirty-one percent (13/42) of 42 patients assessable
      for p16 gene methylation showed to be methylation-positive. High-angiogenesis was
      present in 73% of cases, but methylation of the p16 gene did not associate with
      angiogenesis or with VEGF expression. Also, p16 methylation did not show
      prognostic relevance or correlation with the clinical and laboratory parameters
      of prognostic significance in univariate analysis. P16 immunoexpression presented
      only a faint agreement with the molecular study. Therefore, p16 methylation seems
      to have no correlation with angiogenesis and VEGF expression, neither with
      overall and event-free survival in MM patients. Besides, P16 immunohistochemistry
      seems inadequate to substitute the molecular study of methylation in this type of
      tumor cells. Additional studies are needed to clarify the correspondence between
      the epigenetic alteration of the p16 gene and its protein immunexpression, and
      the clinical relevance of p16 methylation in MM patients.

PMID- 15863275
TI  - Studies on antigenic and genomic properties of Brazilian rabies virus isolates.
AB  - Despite the recognized stability of rabies virus, differences among isolates from
      different species have been found. This work was carried out with the aim to
      identify antigenic and genomic differences in Brazilian rabies virus isolates and
      to verify whether such alterations would bear any relationship with the different
      hosts for the virus in nature. For that, 79 Brazilian rabies viruses isolated
      from different host species and from distinct regions within Brazil were
      submitted to antigenic characterization with a panel of 11 monoclonal antibodies
      (Mabs) directed to lyssavirus antigens and to genomic analyses by the reverse
      transcriptase-polymerase chain reaction (RT-PCR) amplification of the N gene
      followed by restriction endonuclease analysis (REA). In addition, the nucleotide
      sequences of part of the N gene (225 bp) of seven isolates, taken as
      representative of the majority of the viruses under study, were determined. The
      analyses with the Mabs and RT-PCR/REA allowed the identification of two major
      groups of variants, the first formed by most isolates of cattle and bats and the
      second formed by viruses of dog origin. Partial sequencing of the N gene
      confirmed the similarity among isolates from cattle origin and those of vampire
      bats. However, viruses from non-haematophagous bats exhibited consistent
      differences from those of vampire bat isolates. Such findings suggest that the
      variants have evolved fairly stable modifications, which are not altered after
      passage in a dead-end host of a distinct species. No association could be
      established between antigenic or genomic alterations and geographic distribution
      of the isolates, which suggests that evolution of the virus has been directed to
      adaptation to the host species.

PMID- 15863276
TI  - Genetic variability of PRRS virus in Austria: consequences for molecular
      diagnostics and viral quantification.
AB  - Porcine reproductive and respiratory syndrome virus is a virus with a relatively
      high level of sequence variation, especially between the European and the
      American-type strains. This high degree of sequence variations will influence the
      accuracy of results obtained by molecular diagnostic methods, especially if
      mutations are located in the primer or probe binding regions of PCR or real-time
      PCR based assays. In order to provide the basis for the development of an
      accurate, region-tailored assay we have analysed samples obtained from several
      Austrian pig herds using a series of RT-PCR assays. Subsequent sequencing of the
      PCR products from ORF5 and phylogenetic analysis revealed the occurrence of both
      the European and the American-type of porcine reproductive and respiratory
      syndrome virus in Austria. Since vaccination with the American-type vaccine is
      not authorized in Austria the import of vaccinated animals is the most likely
      explanation for the occurrence of these strains. The study highlights the
      importance of a detailed study on the sequence variations occurring in the region
      of interest before the development of a reliable PCR-based assay.

PMID- 15863277
TI  - Molecular characterization of the major outer membrane protein of Haemophilus
      somnus.
AB  - The major outer membrane protein (MOMP) of Haemophilus somnus shows antigenic and
      molecular mass diversity that forms the basis of a preliminary grouping system
      for H. somnus strains. In this study, the gene encoding MOMP of H. somnus strain
      8025 was cloned in three overlapping fragments by PCR techniques, and then
      sequenced. The gene consists of a 1164-bp open reading frame encoding a deduced
      380-amino acid protein with a 19-amino acid signal sequence, giving a mature
      protein with a calculated molecular mass of 39,913 Da. Significant homology was
      found between MOMP and porin protein sequences of bacteria in Pasteurellaceae
      species. When expressed in Escherichia coli, the protein from the MOMP gene
      directed by the T7 promoter was identical in size (approximately 40 kDa) to
      native MOMP and reacted with MOMP-specific antibodies. Comparisons of the MOMP
      gene sequences from six unrelated strains of H. somnus to that of strain 8025
      revealed that the genes of three MOMP type 1 strains were highly conserved with
      that of strain 8025 in length and sequence. However, two MOMP type 3c strains and
      one MOMP type 3a strain differed markedly from the MOMP of strain 8025 in their
      3'-terminal halves. Their deduced MOMP amino acid sequences differed in sequence
      (3c, 80.5 and 82.7% identity; 3a, 62.4% identity) and in length (3c, 384 and 376;
      3a, 316), indicating that the molecular differences are the basis of antigenicity
      and molecular mass differences of H. somnus MOMP. In the predicted MOMP secondary
      structure, the variable sequences primarily mapped to putative surface-exposed
      loops, and a variable and surface-exposed epitope of MOMP-specific antibody was
      identified in the seventh-largest loop. These findings are useful for
      understanding the structural and immunological characteristics of H. somnus.

PMID- 15863278
TI  - A longitudinal study of Escherichia coli O157 in cattle of a Dutch dairy farm and
      in the farm environment.
AB  - From July 1999 till November 2000, a longitudinal study was conducted on a dairy
      farm in The Netherlands to study within herd prevalence and types of
      verocytotoxin producing Escherichia coli (VTEC) of serogroup O157 over time, and
      determine environmental reservoirs and possible transmission routes. Faeces,
      blood, milk and environmental samples were collected 14 times with intervals
      varying from 4 to 10 weeks during the study period. Faecal samples were
      selectively cultured for Escherichia coli O157. Isolates were tested by PCR for
      the most common virulence genes, VTI, VTII and eae, and typed by pulsed field gel
      electrophoresis. In total, 71 isolates were obtained, of which 49 from dairy
      cows, 8 from young stock, 5 from other animals and 9 from the environment.
      Positive samples were all detected in summer and early fall. VT- and eae-genes
      were found in all tested isolates, except in one. DNA typing showed that three
      clusters of O157 isolates could be identified. One of these clusters contained
      samples of two shedding seasons, indicating persistence on the farm during winter
      and spring. Repeated measures analysis of variance showed that cows with O157
      VTEC infection had higher daily milk production in the period preceding sampling
      (p = 0.0055). There was no significant association between the results of the LPS
      ELISA on serum samples from dairy cows and their O157 status.

PMID- 15863279
TI  - Survival of Salmonella serovar Typhimurium inside porcine monocytes is associated
      with complement binding and suppression of the production of reactive oxygen
      species.
AB  - The development of the carrier state in swine after infection with Salmonella
      serovar Typhimurium (S. Typhimurium) has not been elucidated yet. Possibly,
      phagocytes like macrophages play a crucial role. It was the aim of the present
      study to characterize the interaction of a S. Typhimurium strain and its hilA and
      ssrA mutants with porcine peripheral blood monocytes (PBM). Exposure of porcine
      PBM to S. Typhimurium induced the production of reactive oxygen species (ROS),
      requiring bacterial protein synthesis. The numbers of intracellular bacteria
      sharply decreased over a period of 3h. Monocytes obtained from different pigs
      differed markedly in their ROS production and in their ability to kill the
      bacteria. Interestingly, high ROS production did not coincide with increased
      intracellular killing. Using diphenylene iodonium inhibition of nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase activity, it was shown that
      bacterial killing was ROS-dependent only within 1h post inoculation, but was ROS
      independent from 1h post inoculation onwards. This might be explained by the
      finding that metabolically active Salmonella bacteria were capable of suppressing
      the respiratory burst activity in a SPI-1- and SPI-2-independent manner without
      causing measurable cell damage. Opsonization with complement did not alter the
      ROS production. Nevertheless, it increased intracellular survival of the
      bacteria. In conclusion, survival of S. Typhimurium inside porcine PBM is
      promoted by suppression of respiratory burst activity and complement binding.

PMID- 15863280
TI  - Antimicrobial susceptibility and molecular characterization of avian pathogenic
      Escherichia coli isolates.
AB  - Ninety-five avian pathogenic Escherichia coli (APEC) isolates recovered from
      diagnosed cases of avian colibacillosis from North Georgia between 1996 and 2000
      were serotyped and examined for typical virulence-factors, susceptibility to
      antimicrobials of human and veterinary significance, and genetic relatedness.
      Twenty different serotypes were identified, with O78 being the most common (12%).
      The majority of the avian E. coli isolates (60%), however, were non-typeable with
      standard O antisera. Eighty-four percent of isolates were PCR positive for the
      temperature-sensitive hemagglutinin (tsh) gene and 86% positive for the increased
      serum survival (iss) gene. Multiple antimicrobial-resistant phenotypes (> or =3
      antimicrobials) were observed in 92% of E. coli isolates, with the majority of
      isolates displaying resistance to sulfamethoxazole (93%), tetracycline (87%),
      streptomycin (86%), gentamicin (69%), and nalidixic acid (59%). Fifty-six E. coli
      isolates displaying resistance to nalidixic acid were co-resistant to difloxacin
      (57%), enrofloxacin (16%), gatifloxacin (2%), and levofloxacin (2%). DNA
      sequencing revealed point mutations in gyrA (Ser83-Leu, Asp87-Tyr, Asp87-Gly,
      Asp87-Ala), gyrB (Glu466-Asp, Asp426-Thr), and parC (Ser80-Ile, Ser80-Arg). No
      mutations were observed in parE. Twelve of the quinolone-resistant E. coli
      isolates were tolerant to cyclohexane, a marker for upregulation of the acrAB
      multi-drug resistance efflux pump. Quinolone-resistant isolates were further
      genetically characterized via ribotyping. Twenty-two distinct ribogroups were
      identified, with 61% of isolates clustering into four major ribogroups,
      indicating that quinolone resistance has emerged among multiple avian pathogenic
      E. coli serogroups and chromosomal backgrounds.

PMID- 15863281
TI  - Characterization of the type I secretion system of the RTX toxin ApxII in
      "Actinobacillus porcitonsillarum".
AB  - Strains of Actinobacillus porcitonsillarum are regularly isolated from the
      tonsils of healthy pigs. A. porcitonsillarum is non pathogenic but phenotypically
      it strongly resembles the pathogenic species Actinobacillus pleuropneumoniae,
      thereby interfering with the diagnosis of the latter. A. porcitonsillarum is
      hemolytic but unlike A. pleuropneumoniae, it contains only apxII genes and not
      apxI or apxIII genes. In contrast to the truncated apxII operon of A.
      pleuropneumoniae, which lacks the type I secretion genes BD, characterization of
      the apxII operon in A. porcitonsillarum revealed that it contains an intact and
      complete apxII operon. This shows a typical RTX operon structure with the gene
      arrangement apxIICABD. The region upstream of the apxII operon is also different
      from that in A. pleuropneumoniae and contains an additional gene, aspC, encoding
      a putative aspartate aminotransferase. Trans-complementation experiments in
      Escherichia coli and A. pleuropneumoniae indicated that the entire apxII operon
      of A. porcitonsillarum is sufficient to express and secrete the ApxIIA toxin and
      that the ApxIIA toxin of A. pleuropneumoniae can be secreted by the type I
      secretion system encoded by apxIIBD. These findings suggest that the complete
      apxII operon found in A. porcitonsillarum might be an ancestor of the truncated
      homologue found in A. pleuropneumoniae. The genetic context of the apxII locus in
      A. porcitonsillarum and A. pleuropneumoniae suggests that in the latter, the
      contemporary truncated operon is the result of a recombination event within the
      species, rather than a horizontal transfer of an incomplete operon.

PMID- 15863282
TI  - Investigation and control of an outbreak of salmonellosis caused by multidrug
      resistant Salmonella typhimurium in a population of hospitalized horses.
AB  - An outbreak of salmonellosis in a population of hospitalized horses resulted in
      the closure of a teaching hospital for a period of 10 weeks. Fecal samples were
      collected from suspected cases and cultured for Salmonella. Salmonella isolates
      were characterized using antimicrobial susceptibility testing, pulsed-field gel
      electrophoresis (PFGE) and phage typing. Thirty-three cases of infection by a
      multidrug-resistant strain of S. typhimurium were detected. The index case was
      admitted on 26 August 1999. Fifteen (45%) cases occurred between April and June
      2000. PFGE results suggested that this strain of S. typhimurium might have been
      introduced into the hospital environment by a foal presenting with diarrhea. The
      hospital was closed on June 13, and intensive environmental cleaning and
      disinfection were completed. Enforcement of infectious disease control protocols
      in hospitals and environmental and patient surveillance is needed to prevent
      outbreaks of salmonellosis.

PMID- 15863283
TI  - Buenos Aires, a new Leptospira serovar of serogroup Djasiman, isolated from an
      aborted dog fetus in Argentina.
AB  - This study describes the isolation of a new leptospiral serovar from the Djasiman
      group from an Argentinean aborted fetus of a dog. The strain was isolated from a
      culture of mixed liver and kidney tissue from one aborted dog fetus. Bitch's
      serum showed a titre of 1:800 against the new serovar and 1:400 or less against
      other serovars tested. Microscopic Agglutination test (MAT) with a panel of 38
      rabbit anti-Leptospira sera representative for all pathogenic serogroups was
      performed to establish the putative serogroup of the isolated strain. Serovar
      identification was done by Cross-Agglutination Absorption Test (CAAT). Species
      determination was carried out on basis of sequence identity of primer pair G1/G2
      generated PCR products from the isolate with those from reference strains
      belonging to the various pathogenic Leptospira species. Results showed that the
      new strain named, Baires, belongs to species L. interrogans sensu stricto and the
      serogroup Djasiman. However, the isolate could not be identified as any of the
      known serovars within this serogroup. These results allow us to conclude that the
      strain Baires represents a new serovar (Buenos Aires) of Djasiman serogroup.

PMID- 15863284
TI  - The distribution of bmpB, a gene encoding a 29.7 kDa lipoprotein with homology to
      MetQ, in Brachyspira hyodysenteriae and related species.
AB  - The distribution of the bmpB gene encoding BmpB, a 29.7 kDa outer membrane
      lipoprotein of the intestinal spirochaete Brachyspira hyodysenteriae, was
      investigated. Using PCR, the gene was detected in all the 48 strains of B.
      hyodysenteriae examined and in Brachyspira innocens strain B256T, but not in 11
      other strains of B. innocens nor in 42 strains of other Brachyspira spp. The gene
      was sequenced from B. innocens strain B256T and from 11 strains of B.
      hyodysenteriae. The B. hyodysenteriae genes shared 97.9-100% nucleotide sequence
      similarity and had 97.5-99.5% similarity with the gene of B. innocens strain
      B256T. Southern hybridisation indicated that bmpB was present on a 1.9 kb HindIII
      fragment of the B. hyodysenteriae genome and on a 3.1 kb fragment of the B.
      innocens B256T genome. The B. innocens lipoprotein did not react in Western blots
      with monoclonal antibody BJL/SH1 that reacts with the B. hyodysenteriae
      lipoprotein. The difference in binding with the monoclonal antibody may reside in
      the replacement of a serine residue with a tyrosine residue at base position 210
      in the lipoprotein from B. innocens B256T. Comparison of the BmpB amino acid
      sequence with sequences in the SWISS-PROT protein database indicated that it has
      33.9-39.9% similarity with the d-methionine binding proteins (MetQ) of a number
      of pathogenic bacterial species. The bmpB gene was confirmed to be the same as a
      gene of B. hyodysenteriae that was recently designated "blpA".

PMID- 15863285
TI  - Fecal shedding of Mycobacterium avium subsp. paratuberculosis by dairy cows.
AB  - Between 1982 and 2000, fecal samples were obtained from 786 cows that were
      shedding Mycobacterium avium subsp. paratuberculosis (Map). These cows were
      resident on 93 Pennsylvania dairies (mean herd size, 64 milk cows) that had no or
      minimal previous testing for Map. Feces were cultured on four tubes of Herrold's
      egg yolk medium and the distribution of mean Map colony forming units (CFU) was
      evaluated. Most cows were light (< 10 CFU/tube, 51.4%) or high (> 50 CFU/tube,
      30.8%) fecal shedders with fewer cows in the moderate category (10-50 CFU/tube).
      Of the 786 cows, 192 (24.4%) had colonies in only one of four tubes. In the
      multivariable negative binomial model, there were significant associations
      between mean CFU/tube and prevalence, herd size, and season and an interaction
      between herd size and season. The linear mixed model of continuous tube counts
      with a random herd effect yielded similar findings with associations with herd
      size as a continuous variable, season, and an interaction between categorized
      prevalence and continuous herd size. Variability in CFU/tube was greatest among
      cows in the same herd, intermediate for replicate tubes from the same cow, and
      smallest among cows in different herds. Reduction in the number of replicate
      tubes from four would have reduced the sensitivity of fecal culture for Map by
      approximately 6% (for three tubes) to 12% (for two tubes).

PMID- 15863286
TI  - Neuraminidase production by Erysipelothrix rhusiopathiae.
AB  - In order to characterise neuraminidase activity by Erysipelothrix, 85 isolates of
      Erysipelothrix spp. from a variety of sources including human clinical, marine
      and terrestrial animals, and the environment were investigated for neuraminidase
      production. Neuraminidase activity was detected by a peanut lectin
      haemagglutination method. The effects of media, incubation conditions and pH on
      the production and activity of neuraminidase were also investigated. Enzyme
      activity was detected only in the supernatants of the isolates of Erysipelothrix
      rhusiopathiae which had been incubated in cooked meat broth and Todd Hewitt broth
      supplemented with horse serum after 16 and 36 h incubation at 37 degrees C. The
      maximum titres were reached at 40 h in cooked meat broth and 56 h in Todd Hewitt
      broth supplemented with horse serum. All 58 isolates and the type strain (ATCC
      19414) of E. rhusiopathiae produced detectable neuraminidase activity with titres
      between 10 and 320. The optimal pH for the enzyme activity varied among the
      isolates with a pH between 6.0 and 7.0 covering the highest enzyme activity of
      the most. There was no statistically significant difference in the level of
      neuraminidase activity between isolates from different sources (p > 0.05).
      Neuraminidase activity was not detected in the non-pathogenic Erysipelothrix spp.
      such as E. tonsillarum. Neuraminidase was detected only in E. rhusiopathiae
      suggesting its possible role as a virulence factor. Enzyme production and
      activity were medium and pH dependent. The peanut lectin haemagglutination assay
      is a simple, rapid and sensitive method and is particularly useful for the
      analysis of multiple samples.

PMID- 15863287
TI  - Quantification of Ehrlichia ruminantium by real time PCR.
AB  - Ehrlichia ruminantium (ER) is the causative agent of Heartwater, one of the most
      common tick-borne diseases affecting ruminants in African countries and West
      Indies. Although ER can be used as an inactivated vaccine for wild and domestic
      animals, there are currently no easy and reliable methods for the quantification
      of this obligate intracellular bacterium. This report describes the development
      of a SYBR Green I based real time PCR protocol for the quantification of ER for
      vaccine production purposes. The method was validated for four ER strains. The
      external-standard-based PCR protocol developed has a large dynamic quantitative
      range allowing accurate ER measurement in samples containing from 10(2) to 10(8)
      gene copies; the method is also reproducible and precise, with intra- and inter
      assay coefficients below 5%. The detection limits were validated for samples
      collected from bovine aortic endothelial cell culture bulks, which are commonly
      used to produce the ER vaccine. In contrast to the methods based upon protein
      content, no interference from the host cells in ER quantification was observed.
      Furthermore, the extended applicability of the new technique was demonstrated by
      monitoring ER production in cell culture thus rendering it a valuable tool to
      ensure consistency between vaccine lots and to evaluate optimal vaccine dosage.

PMID- 15863288
TI  - Validation of chemoprevention of canine monocytic ehrlichiosis with doxycycline.
AB  - Epidemiological (cohort follow-up) and laboratory techniques studies were done to
      validate a programme of chemoprevention of canine monocytic ehrlichiosis (CME)
      with this molecule. 614 dogs returning to France after having spent at least 4
      months in a CME-endemic area (Africa, Guyana, Middle-East, etc.) were the object
      of systematic serological testing by indirect immunofluorescence (IFA). The dogs
      were given 100 mg of doxycycline per os daily for chemoprevention of CME. In
      addition, HPLC (high performance liquid chromatography) was used to determine
      plasma levels of doxycycline in 124 of the dogs. The CEM mortality and morbidity
      rates for the 614 dogs in the chemoprevention programme were nil. The
      seroconversion rate was 4% (24/614). Seropositive dogs (low titres) were
      asymptomatic and generally became seronegative after treatment. A study done on
      10 dogs shows that doxycyclinaemia was 1.2 (0.94-1.53) microg/ml 2 h after the
      drug had been administered. After 24 h, the residual concentration was 0.34 (0.26
      0.44) microg/ml. Blind doxycyclinaemia tests done on 110 dogs living in Africa
      (the results for four dogs were nil and therefore eliminated from the study)
      showed that the minimum observed concentration was always greater than 0.2
      microg/ml. Given that, as concerns infection with Ehrlichia spp., the minimum
      inhibitory concentration of doxycycline is < or = 0.03 microg/ml, dogs receiving
      chemoprevention treatment should be protected.

PMID- 15863289
TI  - Antibiotic treatment of experimentally Borrelia burgdorferi-infected ponies.
AB  - The objective of this study is to determine whether doxycycline, ceftiofur or
      tetracycline could be effectively used to treat equine Lyme disease. Ponies
      experimentally infected with Borrelia burgdorferi by tick exposure were treated
      with doxycycline, ceftiofur or tetracycline for 4 weeks (28 days). Doxycyline and
      ceftiofur treatment were inconsistent in eliminating persistent infection in this
      experimental model. However, tetracycline treatment seems to eliminate persistent
      infection. Although serum antibody levels to B. burgdorferi in all ponies
      declined gradually after antibiotic treatment, three out of four ponies treated
      with doxycline and two out of four ponies treated with ceftiofur, serum KELA
      titers were raised again 3 month after treatment was discontinued. Five months
      after antibiotic treatment, tissues aseptically collected at necropsy from ponies
      with increased antibody levels after antibiotic treatment also showed culture
      positive to B. burgdorferi in various post-mortem tissues. However, all four
      tetracycline treatment ponies showed a negative antibody level and culture
      negative from post-mortem tissues. Untreated infected ponies maintained high KELA
      titers throughout the study and were tissue culture positive.

PMID- 15863290
TI  - Biofilm production by Staphylococcus aureus associated with intramammary
      infection.
AB  - Biofilm production by 221 Staphylococcus aureus isolates from 45 dairy herds was
      evaluated. Isolates were from composite milk of 117 cows, from teat skin of 70
      cows, and from 34 milking machine unit liners. Of S. aureus from milk samples,
      41.4% were biofilm producers, as compared to 24.7 and 14.7% of the isolates
      collected from skin and liners. Pulsed field gel electrophoresis (PFGE) best
      categorized S. aureus biofilm producers as compared to phage typing and binary
      typing. PFGE types that were significantly associated with isolation from milk as
      opposed to teat skin or liners, had isolates that were more likely to produce
      biofilm than PFGE types that were isolated from milk, skin and liners at similar
      frequencies. By contrast, PFGE type A was significantly associated with isolation
      from teat skin and had few biofilm producers. PFGE type Q, which is exclusively a
      milk, isolate produced more biofilm as evidenced by absorbance values. Given S.
      aureus that are associated with milk are more likely to produce biofilm as
      compared to extramammary sources (teat skin and milking unit liners), suggests
      that biofilm production is a risk factor for infection.

PMID- 15863291
TI  - Insertion sequence profiling of UK Mycoplasma bovis field isolates.
AB  - The presence and distribution of insertion sequences ISMbov2 and ISMbov3 within
      Mycoplasma bovis were investigated. Analysis was carried out by Southern blotting
      using specific probes of 221 bp and 185 bp, to detect ISMbov2 and ISMbov3,
      respectively, amplified from the homologous sequences ISMmy1 and IS1634 within
      Mycoplasma mycoides subspecies mycoides small colony type. We present data
      obtained from 49 field isolates of M. bovis, originating from pneumonic lungs,
      collected within the United Kingdom between 1996 and 2002. Hybridisation profiles
      show considerable variation between strains. ISMbov2 sequences are present
      between 2 and 17 copies while there are between 3 and 14 copies of the IS1634
      homologue ISMbov3. These data also provide support for previous analysis by
      random amplified polymorphic DNA (RAPD) and amplified fragment length
      polymorphism (AFLP).

PMID- 15863292
TI  - Role of HdeA in acid resistance and virulence in Brucella abortus 2308.
AB  - Two-dimensional gel electrophoretic analysis of cell lysates suggests that
      stationary phase production of wild-type levels of an ortholog of the low pH
      dependent chaperone HdeA in Brucella abortus 2308 during growth in a minimal
      medium requires the presence of the RNA binding protein Hfq. Although mutational
      analysis demonstrated that HdeA contributes to acid resistance in this bacterium,
      this protein is not required for wild-type virulence in the BALB/c mouse model.
      These experimental findings indicate that the brucellae rely upon additional gene
      products to resist the acidic conditions they encounter in the phagosomal
      compartment of host macrophages.

PMID- 15863293
TI  - Selective PPARgamma modulators with improved pharmacological profiles.
AB  - A series of metabolically robust N-benzyl-indole selective PPARgamma modulators
      with either a 3-benzoyl or 3-benzisoxazoyl moiety have been identified. In vitro,
      these compounds are partial agonists and exhibit reduced adipogenesis in human
      adipocytes. In vivo, these SPPARgammaMs result in potent glucose lowering in
      db/db mice and attenuate increases in heart weight and brown adipose tissue that
      is typically observed in rats upon treatment with PPARgamma full agonists.

PMID- 15863295
TI  - Site-specific immobilization of proteins in a microarray using intein-mediated
      protein splicing.
AB  - One of the critical issues in the generation of a protein microarray lies in the
      choice of immobilization strategies, which ensure proteins are adhered to the
      glass surface while properly retaining their native biological activities.
      Herein, we report a bacterium-based, intein-mediated strategy to generate N
      terminal cysteine-containing proteins which are then chemoselectively immobilized
      to a thioester-functionalized glass slide to generate the corresponding protein
      microarray. We also showed preliminary data of the strategy in a yeast host
      system.

PMID- 15863294
TI  - 1-((S)-gamma-substituted prolyl)-(S)-2-cyanopyrrolidine as a novel series of
      highly potent DPP-IV inhibitors.
AB  - 1-(Gamma-substituted prolyl)-(S)-2-cyanopyrrolidines were designed based on the
      predicted binding mode of the known DPP-IV inhibitor NVP-DPP728 and evaluated for
      their inhibitory activity. In structure-activity relationship study at the gamma
      position of proline, it became clear that compounds bearing (S)-stereochemistry
      were 20-fold more potent than the antipode. Of these compounds, the (3,4
      dicyanophenyl)amino- and (3-chloro-4-cyanophenyl)amino-derivatives showed the
      highest inhibitory activity.

PMID- 15863296
TI  - Synthesis of dehydroalanine fragments as thiostrepton side chain mimetics.
AB  - Syntheses of dehydroalanine derivatives via a solid-support route, starting from
      selenocystein, and via conventional solution phase chemistry are described along
      with initial biological testing. The target compounds were designed as mimetics
      of the dehydroalanine side chain of the macrocyclic antibiotic thiostrepton that
      acts on the bacterial ribosome.

PMID- 15863297
TI  - Discovery of novel conformationally constrained tropane-based biaryl and
      arylacetylene ligands as potent and selective norepinephrine transporter
      inhibitors and potential antidepressants.
AB  - To further explore the structure-activity relationships of conformationally
      constrained tropanes, a number of new biaryl and arylacetylene analogs were
      designed and synthesized. Some of these compounds such as 3a-b, 3d, 3f-h, 5b, and
      7g were found to be highly potent and selective or mixed norepinephrine
      transporter (NET) inhibitors with Ki values of 0.8-9.4 nM. Moreover, all of these
      compounds display weak to extremely weak muscarinic receptor binding affinity,
      indicating that as potential antidepressants, they may overcome certain side
      effects that are of concern with other antidepressants, which are thought to be
      mediated by their anticholinergic properties.

PMID- 15863298
TI  - 6-Hydroxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid mimics active
      conformation of tyrosine in opioid peptides.
AB  - 6-Hydroxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid (6Htc) has been
      proposed as a rigid mimic of tyrosine conformation in opioid ligand-receptor
      complex. The significant receptor binding to mu and delta opioid receptors of
      respective analogues of deltorphin, dermorphin, and endomorphin with D,L-6Htc
      prove initial prediction.

PMID- 15863299
TI  - Synthesis and biological evaluation of new biphalin analogues with non-hydrazine
      linkers.
AB  - Biphalin is a potent opioid peptide agonist, with a palandromic structure,
      composed of two enkephalin-like active fragments connected tail to tail by a
      hydrazine linker (Tyr-D-Ala-Gly-Phe-NH-NH<-Phe<-Gly<-D-Ala<-Tyr). This study
      presents the synthesis and in vitro bioassays of six new biphalin analogues with
      three different non-hydrazine linkers, some of which have higher binding affinity
      and bioactivity than biphalin.

PMID- 15863300
TI  - A facile route to paclitaxel C-10 carbamates.
AB  - A general protocol for the synthesis of paclitaxel C-10 carbamates is described.
      The method entails MeI-mediated activation of 2'-O-TBS-7-O-TES-10-O-deacetyl
      paclitaxel-10-O-carbonylimidazole prior to reaction with amines. This method is
      effective for the synthesis of paclitaxel C-10 derivatives, including
      bifunctional molecules.

PMID- 15863301
TI  - Inhibitors of HCV NS5B polymerase. Part 1: Evaluation of the southern region of
      (2Z)-2-(benzoylamino)-3-(5-phenyl-2-furyl)acrylic acid.
AB  - A novel series of nonnucleoside HCV NS5B polymerase inhibitors were prepared from
      (2Z)-2-(benzoylamino)-3-(5-phenyl-2-furyl)acrylic acid, a high throughput
      screening lead. SAR studies combined with structure based drug design focusing on
      the southern heterobiaryl region of the template led to the synthesis of several
      potent and orally bioavailable lead compounds. X-ray crystallography studies were
      also performed to understand the interaction of these inhibitors with HCV NS5B
      polymerase.

PMID- 15863302
TI  - Antiproliferative activity in HL60 cells by tetrasubstituted pyrroles: a
      structure-activity relationship study.
AB  - A number of tetrasubstituted pyrrole derivatives have been synthesized and
      evaluated for their in vitro antiproliferative activities using the human
      promyelocytic leukemia cell line HL60. Tetrasubstituted pyrroles are obtained by
      irradiation of a silica gel absorbed mixture of a conjugated alkynoate and a
      primary amine. Active compounds exhibited GI50 values in the range 4-45 microM,
      and only six products showed TGI values within the evaluation range. A structure
      activity relationship is also discussed.

PMID- 15863303
TI  - EB1627: a soluble prodrug of the potent anticancer cyanoguanidine CHS828.
AB  - To overcome pharmacokinetic and solubility problems observed in early clinical
      trials with the potent anticancer compound CHS828, we synthesised a series of
      prodrugs with improved properties. The best compound obtained was EB1627, with a
      tetraethyleneglycol moiety attached to the parent drug via a carbonate linkage.
      This compound was found soluble enough to be given i.v. and the drug was rapidly
      released in vivo exerting a very potent inhibitory activity alone and in
      combination with known cytostatics (etoposide) in animal models in vivo.

PMID- 15863304
TI  - Synthesis and bladder smooth muscle relaxing properties of substituted 3-amino-4
      aryl-(and aralkyl-)cyclobut-3-ene-1,2-diones.
AB  - We have reported on the design, synthesis, and biological characterization of (R)
      4-[3,4-dioxo-2-(1,2,2-trimethyl-propylamino)-cyclobut-1-enylamino]-3-ethyl
      benzonitrile (1), a novel, potent, and selective adenosine 5'-triphosphate
      sensitive potassium (K(ATP)) channel opener with potential utility for the
      treatment of urge urinary incontinence (UUI). Excising the aniline-derived
      nitrogen atom of 1 or replacing it with an aralkyl group, led to bladder smooth
      muscle relaxant chemotypes 3 and 4, respectively. Prototype compounds in these
      series were found to produce significant increases in an iberiotoxin (IbTx)
      sensitive hyperpolarizing current, thus suggesting that these relatively modest
      structural modifications resulted in a switch in the mechanism of action of these
      smooth muscle relaxants from K(ATP) channel openers to activators of the large
      conductance Ca2+-activated potassium channel (BK(Ca)). We report herein the
      syntheses and biological evaluation of a series of substituted 3-amino-4-aryl
      (and aralkyl-)cyclobut-3-ene-1,2-diones.

PMID- 15863305
TI  - Structure-based design of protein tyrosine phosphatase-1B inhibitors.
AB  - Using structure-based design, a new class of inhibitors of protein tyrosine
      phosphatase-1B (PTP1B) has been identified, which incorporate the 1,2,5
      thiadiazolidin-3-one-1,1-dioxide template.

PMID- 15863306
TI  - In vitro advanced antimycobacterial screening of isoniazid-related hydrazones,
      hydrazides and cyanoboranes: part 14.
AB  - As a part of an ongoing search for new isoniazid-related isonicotinoylhydrazones
      (ISNEs), 2'-monosubstituted isonicotinohydrazides and cyanoboranes, some
      analogues belonging to these three series of compounds were further evaluated in
      an in vitro advanced antimycobacterial screening. The results here reported
      allowed us to extend their structure-activity relationships. A general
      correlation emerged between their lipophilicity and effectiveness against
      intracellular M. tuberculosis. On the whole, the most interesting result of this
      research was that some hydrazides and ISNEs proved to be more effective
      antimycobacterial agents than parental isoniazid in a TB-infected macrophage
      model.

PMID- 15863307
TI  - A synthetic route to a novel type of conformationally constrained N
      aryloxazolidinones.
AB  - The synthesis of N-aryloxazolidinone 1, a conformationally constrained analog of
      linezolid embodying a tricyclic pyrrolo[1,2-a][4,1]benzoxazepine moiety as the N
      aryl substituent, is reported. The synthetic route involves the successive
      construction of the pyrrole, oxazepine, and oxazolidinone rings, with
      incorporation of the isoxazolylamino moiety in the last synthetic steps.

PMID- 15863308
TI  - Uracils as potent antagonists of the human gonadotropin-releasing hormone
      receptor without atropisomers.
AB  - Uracil derivatives were designed and synthesized to avoid atropisomers observed
      in the 6-methyluracils as antagonists of the human GnRH receptor. Optimization at
      the 1- and 5-positions of the uracil resulted in potent compounds such as 24
      (Ki=0.45 nM).

PMID- 15863309
TI  - Lactams as prostanoid receptor ligands. Part 4: 2-Piperidones as selective EP4
      receptor agonists.
AB  - 2-Piperidones were prepared bearing heptanoic acid or a thioether heptanoic acid
      at the 1-position as well as appropriately substituted at the 6-position to mimic
      the structure of prostaglandins. The stereochemical purity at the 6-position was
      determined to be 95% ee for an advanced synthetic intermediate. The 2-piperidones
      were identified as potent agonists at the EP4 prostanoid receptor. They displayed
      a high affinity (Ki 5-130 nM) at EP4 and subtype selectivity.

PMID- 15863310
TI  - 4-Alkyl and 4,4'-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione
      derivatives as new inhibitors of bacterial cell wall biosynthesis.
AB  - Over 195 4-alkyl and 4,4-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione
      derivatives were synthesized, utilizing microwave accelerated synthesis, for
      evaluation as new inhibitors of bacterial cell wall biosynthesis. Many of them
      demonstrated good activity against MurB in vitro and low MIC values against gram
      positive bacteria, particularly penicillin-resistant Streptococcus pneumoniae
      (PRSP). Derivative 7l demonstrated antibacterial activity against both gram
      positive and gram-negative bacteria. Derivatives 7f and 10a also demonstrated
      potent nanomolar Kd values in their binding to MurB.

PMID- 15863311
TI  - Discovery of potent and selective phenylalanine based dipeptidyl peptidase IV
      inhibitors.
AB  - anti-Substituted beta-methylphenylalanine derived amides have been shown to be
      potent DPP-IV inhibitors exhibiting excellent selectivity over both DPP8 and
      DPP9. These are among the most potent compounds reported to date lacking an
      electrophilic trap. The most potent compound among these is 5-oxo-1,2,4
      oxadiazole 44, which is a 3 nM DPP-IV inhibitor.

PMID- 15863312
TI  - Design, new synthesis, and calcilytic activity of substituted 3H-pyrimidin-4
      ones.
AB  - Design, new synthesis, structure-activity relationship studies and calcium
      receptor antagonist (calcilytic) properties of novel 3H-pyrimidin-4-ones are
      described.

PMID- 15863313
TI  - A potent and selective nonpeptide antagonist of the melanocortin-4 receptor
      induces food intake in satiated mice.
AB  - Optimization on a series of piperazinebenzylamines resulted in analogues with low
      nanomolar binding at the human MC4 receptor but weak affinity (Ki > 500 nM) at
      the MC3 receptor. Compound 14c was identified to be a potent MC4R antagonist (Ki
      = 3.2 nM) with a selectivity of 240-fold over MC3R. It proved to be an
      insurmountable antagonist in a cAMP assay. Compound 14c potently stimulated food
      intake in satiated mice when given by intracerebroventricular administration.

PMID- 15863314
TI  - Redefining the structure-activity relationships of 2,6-methano-3-benzazocines.
      Part 3: 8-Thiocarboxamido and 8-thioformamido derivatives of cyclazocine.
AB  - 8-Position variants of cyclazocine have been made where the phenolic 8-OH was
      replaced by thioamide, amidine, guanidine, urea and thiourea groups. High
      affinity for opioid receptors was observed for the 8-CSNH2 and 8-NHCHS analogues
      indicating that these groups are isosteric with not only the 8-OH but with the
      previously synthesized 8-CONH2 and 8-NHCHO cyclazocine derivatives.

PMID- 15863315
TI  - 3,3-Bisaryloxindoles as mineralocorticoid receptor antagonists.
AB  - Syntheses and SAR studies of 3,3-bisaryloxindole analogues provided potent
      mineralocorticoid receptor (MR) antagonists that were selective over other
      steroid nuclear hormone receptors.

PMID- 15863316
TI  - Structure-activity relationships of arylbenzofuran H3 receptor antagonists.
AB  - An SAR study of histamine H3 receptor antagonists based on substituted (R)-2
      methyl-1-[2-(5-phenyl-benzofuran-2-yl)-ethyl]-pyrrolidines is presented.

PMID- 15863317
TI  - Discovery of 4-(dimethylamino)quinazolines as potent and selective antagonists
      for the melanin-concentrating hormone receptor 1.
AB  - A series of 4-(dimethylamino)quinazoline based antagonists of the melanin
      concentrating hormone receptor 1 (MCH-R1) is described. This series was derived
      from a lead compound, AR129330, identified by HTS of a GPCR-directed library
      using a functional assay with a constitutively activated (CART) form of the
      receptor. The preliminary optimization resulted in the identification of
      compounds 20, 21, and 23.

PMID- 15863318
TI  - Synthesis and biological evaluation of gemcitabine-lipid conjugate (NEO6002).
AB  - A novel gemcitabine-lipid conjugate 5 was synthesized and tested for its in vivo
      efficacy and toxicity. Compound 5 was tested in BxPC-3 human pancreatic tumor
      model in SCID mice and exhibited promising activity and lower toxicity when
      compared with Gemzar.

PMID- 15863319
TI  - Synthesis of thiosemicarbazone and 4-thiazolidinone derivatives and their in
      vitro anti-Toxoplasma gondii activity.
AB  - Thiosemicarbazone and 4-thiazolidinone derivatives were synthesized in one and
      two step, respectively, from thiosemicarbazide, in satisfactory yields. Then, the
      synthesized compounds were submitted to evaluation against host cells infected
      with Toxoplasma gondii. The present studies showed that thiosemicarbazones 2 and
      4-thiazolidinone derivatives 3 were effective against intracellular T. gondii.

PMID- 15863320
TI  - 2,5-Diketopiperazines as potent and selective oxytocin antagonists 1:
      Identification, stereochemistry and initial SAR.
AB  - This paper covers efforts to discover orally active potent and selective oxytocin
      antagonists. Screening pooled libraries identified a novel series of 2,5
      diketopiperazine derivatives with antagonist activity at the human oxytocin
      receptor. We report the initial structure-activity relationship investigations
      and the determination of the stereochemistry of the most potent compounds.

PMID- 15863321
TI  - Iridium-catalyzed oxidative lactonization and intramolecular Tishchenko reaction
      of delta-ketoaldehydes for the synthesis of isocoumarins and 3,4
      dihydroisocoumarins.
AB  - Two new cyclizations of ketoaldehydes have been developed using an Ir-ligand
      bifunctional catalyst. Oxidative lactonization of delta-ketoaldehydes proceeded
      smoothly at room temperature to give coumarin derivatives in excellent yields.
      Intramolecular Tishchenko reaction of delta-ketoaldehydes afforded 3,4
      dihydroisocoumarins in good yields.

PMID- 15863322
TI  - Lambertellol C, a labile and novel biosynthetic congener of lambertellols A and
      B.
AB  - Lambertellol C (1), a labile biosynthetic congener of lambertellols A and B, was
      isolated from a fermentation broth of Lambertella sp. 1346 based on the
      diagnostic isotope patterns in the mass spectrum of a highly labeled sample. The
      CD spectrum of 1 indicated that this lambertellol analogue exists as a racemate.
      The mechanism for this racemization is discussed.

PMID- 15863323
TI  - Optimization of isotope-labeling conditions for lambertellin based on isotope
      patterns observed by mass spectrometry.
AB  - A method for the sensitive analysis of the incorporation level of labeled acetate
      was developed. This method allowed for the optimization of the conditions for
      lambertellin with up to 48% average incorporation of labeled acetate.

PMID- 15863324
TI  - Macrolactonization catalyzed by the terminal thioesterase domain of the
      nonribosomal peptide synthetase responsible for lichenysin biosynthesis.
AB  - The excised terminal thioesterase of the lichenysin nonribosomal peptide
      synthetase was found to be a highly efficient and versatile enzyme. Its activity
      strictly requires the R configuration of the beta-hydroxy fatty acid and the side
      chains of aspartate-5 and isoleucine-7, but tolerates changes in five other
      residues of the substrate. Characterization of this enzyme facilitates future
      effort to engineer the lichenysin synthetase for biotechnological applications.

PMID- 15863325
TI  - Synthesis and evaluation of 3D templates based on a taxane skeleton to circumvent
      P-glycoprotein-associated multidrug resistance of cancer.
AB  - We have developed a practical synthetic route to construct C-aromatic taxane
      derivatives as three-dimension templates by way of intramolecular alkylation. The
      usefulness of synthesized compounds as the core template was evaluated by using a
      newly developed screening system for P-glycoprotein.

PMID- 15863326
TI  - Synthesis and relative bioavailability of meptazinol benzoyl esters as prodrugs.
AB  - Three meptazinol benzoyl esters (1-3) were synthesized as prodrugs to minimize
      the first-pass effect of meptazinol and improve the bioavailability. Among these
      three esters, compound 3 showed better bioavailability than the parent
      meptazinol. Further, the relative regional bioavailability of prodrug 3 was
      evaluated using in situ closed loop study in rats, which showed that prodrug 3
      has higher absorption efficacy in rat intestine. Thusly, prodrug 3 may be worth
      for further development.

PMID- 15863327
TI  - 5-Lipoxygenase inhibitors: convenient synthesis of 4-[3-(4
      heterocyclylphenylthio)phenyl]-3,4,5,6-tetrahydro-2H-pyran-4-carboxamide
      analogues.
AB  - A convenient synthetic route to 4-[3-(4-heterocyclylphenylthio)phenyl]-3,4,5,6
      tetrahydro-2H-pyran-4-carboxamide analogues as 5-LO inhibitors is described. This
      methodology enabled rapid development of structure-activity relationships (SARs)
      leading to improvement of pharmacological properties. Thus, new compounds with
      higher 5-LO inhibitory potency were discovered. The stereo-chemistry requirements
      of the tetrahydropyran ring are also discussed.

PMID- 15863328
TI  - Synthesis and antifungal activity of 5-arylamino-4,7-dioxobenzo[b]thiophenes.
AB  - 5-Arylamino-4,7-dioxobenzo[b]thiophenes 3-6 were synthesized and tested for in
      vitro antifungal activity against Candida and Aspergillus species. 5-Arylamino-6
      chloro-2-(methoxycarbonyl)-4,7-dioxobenzo[b]thiophenes 5 showed, in general, more
      potent antifungal activity against Candida species than the other 4,7
      dioxobenzo[b]thiophenes 3, 4 and 6. The results suggest that 5-arylamino-4,7
      dioxobenzo[b]thiophenes would be potent antifungal agents.

PMID- 15863329
TI  - Synthesis of pyrrolo[2,1-c][1,4]benzodiazepines and their conjugates by azido
      reductive cyclization strategy as potential DNA-binding agents.
AB  - Synthesis of pyrrolo[2,1-c][1,4]benzodiazepines via azido reductive cyclization
      process employing FeCl3-NaI reagent system. This methodology has been extended
      for the preparation of new nicotinamido-pyrrolobenzodiazepine hybrids linked
      through piperazino-alkane-oxy spacers that exhibit good DNA binding affinity.

PMID- 15863330
TI  - A divergent chemoenzymatic route to an intermediate for nucleoside analogues.
AB  - Two regioisomeric isoxazoline monoacetates 1 and 2 were synthesized from the
      corresponding diacetate 3 via PPL or PLE catalyzed hydrolysis. With both the
      enzymes, the initial regioselectivity (approximately 3-4:1) was offset by an
      intramolecular acyl transfer. In addition to a non-enzymatic catalysis for the
      acyl transfer, preliminary experiments do suggest a definite but minor role of
      enzyme for this intramolecular acyl transfer. Compounds 1 and 2 may serve as
      intermediates for nucleoside analogues.

PMID- 15863331
TI  - Synthesis of novel 10-deoxoartemisinins.
AB  - The synthesis of novel 10-deoxoartemisinin derivatives containing heterocyclic
      rings and hydrophilic groups, and their antimalarial activity assessment are
      described. Most of the synthesized derivatives are more potent than artemisinin,
      especially, some of them are 20-25 times more potent than artemisinin to two
      chloroquine-resistant and sensitive clones of P. falciparum.

PMID- 15863332
TI  - Synthesis and antibacterial activity of hydrolytically stable (-)-epicatechin
      gallate analogues for the modulation of beta-lactam resistance in Staphylococcus
      aureus.
AB  - Hydrolytically more stable analogues of (-)-epicatechin gallate (ECg) have been
      synthesised from ECg where an amine or amide function has been substituted for
      the ester linkage that joins the C-ring with the galloyl D-ring. Sub-inhibitory
      concentrations (25 mg/L) of the amide analogue 7, possessing the natural C-3
      stereochemistry, were able to reduce the resistance to oxacillin of three strains
      of methicillin resistant Staphylococcus aureus (BB 568, EMRSA-15 and EMRSA-16)
      comparable to levels achieved with ECg.

PMID- 15863333
TI  - Isolation, characterization and antiplasmodial activity of steroidal alkaloids
      from Funtumia elastica (Preuss) Stapf.
AB  - Bioassay-guided fractionation of the EtOH extract of the stem bark of Funtumia
      elastica resulted in the isolation of four steroidal alkaloids, holarrhetine (1),
      conessine (2), holarrhesine (3) and isoconessimine (4). Their structures were
      determined on the basis of 1D- and 2D-NMR techniques and mass spectrometry.
      Compounds 1-4 exhibited in vitro antiplasmodial activity against the chloroquine
      resistant strain FcB1 of Plasmodium falciparum with IC50 values ranging from 0.97
      to 3.39 microM. They showed weak cytotoxicity against a rat cell line L-6 with
      IC50 values ranging from 5.13 to 36.55 microM.

PMID- 15863334
TI  - Geometry, topology, and atom-weights assembly descriptors to predicting A1
      adenosine receptors agonists.
AB  - The GEometry, Topology, and Atom-Weights AssemblY (GETAWAY) approach has been
      applied to the study of the A1 adenosine receptors agonist effect of 32 adenosine
      analogues: N6-arylcarbamoyl, 2-arylalkynyl-N6-arylcarbamoyl, and N6-carboxamido
      derivatives. A model, able to describe more than 77% of the variance in the
      experimental activity, was developed with the use of the above mentioned
      approach. Five different approaches (Topological, Galvez Topological Charges
      indexes, Randic Molecular Profiles, Geometrical, and WHIM descriptors) failed to
      give satisfactory models (R2=0.70) for this property with the same number of
      variables in the equation. Although statistically significant models were derived
      containing descriptors other than GETAWAY, the best fitted out model was still
      found with these descriptors.

PMID- 15863335
TI  - Arylacetamide kappa opioid receptor agonists with reduced cytochrome P450 2D6
      inhibitory activity.
AB  - Some kappa opioid receptor agonists of the arylacetamide class, for example, ICI
      199441 (1), were found to strongly inhibit the activity of cytochrome P450 2D6
      (CYP2D6) (1: CYP2D6 IC50=26 nM). Certain analogs bearing a substituted
      sulfonylamino group, for example, 13, were discovered to have significantly
      reduced CYP2D6 inhibitory activity (13: CYP2D6 IC50>10 microM) while displaying
      high affinity toward the cloned human kappa opioid receptor, good kappa/delta and
      kappa/mu selectivity, and potent in vitro and in vivo agonist activity.

PMID- 15863336
TI  - Design, synthesis and structure-activity relationships of 6-O-arylpropargyl
      diazalides with potent activity against multidrug-resistant Streptococcus
      pneumoniae.
AB  - A novel series of 6-O-arylpropargyl diazalides was synthesized and evaluated for
      their antibacterial activity. Members of this series exhibited potent activity
      against erythromycin-resistant respiratory tract pathogens.

PMID- 15863337
TI  - Radical scavenging activity of protein from tentacles of jellyfish Rhopilema
      esculentum.
AB  - In this study, radical scavenging activity of protein from tentacles of jellyfish
      Rhopilema esculentum (R. esculentum) was assayed including superoxide anion
      radical and hydroxyl radical scavenging. The protein samples showed strong
      scavenging activity on superoxide anion radical and values EC50 of full protein
      (FP), first fraction (FF), second fraction (SF), and 30% (NH4)2 SO4 precipitate
      (Fr-1) were 2.65, 7.28, 1.10, and 22.51 microg/mL, respectively, while values
      EC50 of BHA, BHT, and alpha-tocopherol were 31, 61, and 88 microg/mL,
      respectively. Also, the protein samples had strong scavenging effect on hydroxyl
      radical and the values EC50 of FP, FF, SF, Fr-1, and Fr-2 were 48.91, 27.72,
      1.82, 16.36, and 160.93 microg/mL, but values EC50 of Vc and mannitol were 1907
      and 4536 microg/mL, respectively. Of the five protein samples, SF had the
      strongest radical scavenging activity and may have a use as a possible supplement
      in the food and pharmaceutical industries. The radical scavenging activity was
      stable at high temperature so that R. esculentum may be used as a kind of natural
      functional food.

PMID- 15863338
TI  - Design and synthesis of novel diphenacoum-derived, conformation-restricted
      vitamin K 2,3-epoxide reductase inhibitors.
AB  - Two novel diphenacoum-derived analogues 5 and 6 are designed, synthesized and
      tested as potential vitamin K 2,3-epoxide reductase (VKOR) inhibitors. The
      inhibition studies indicated that 5 is a potent VKOR inhibitor, which confirmed
      that the replacement of the tetrahydronaphthalene on diphenacoum to a chroman
      functionality does not have a major impact on inhibition potency. The
      conformation-restricted compound 6 is a moderate inhibitor which may serve as a
      lead compound for further study of the mode of action of coumarin-type
      anticoagulants at the molecular level.

PMID- 15863339
TI  - Identification of chemokine receptor CCR4 antagonist.
AB  - The present study reports the identification and hits to leads optimization of
      chemokine receptor CCR4 antagonists. Compound 12 is a high affinity, non
      cytotoxic antagonist of CCR4 that blocks the functional activity mediated by the
      receptor.

PMID- 15863340
TI  - Selective interaction between tylophorine B and bulged DNA.
AB  - Tylophorine B exhibits pronounced cytotoxicity and antitumor activity. In order
      to survey the structure selectivity to DNA afforded by tylophorine B, we have
      synthesized a variety of duplex, bulge- and hairpin-containing
      oligodeoxyribonucleotides. Their binding to tylophorine B has been assayed by
      fluorescence spectroscopy and thermal melting experiments. The results indicate
      that oligonucleotides interact with tylophorine B at submicromolar concentration,
      and the affinity for DNA bulge is optimal (with Kd of 0.018 microM). In addition,
      the bulged hairpin oligonucleotides are stabilized by binding to tylophorine B.
      These findings may shed some light on tylophorine B's mode of action in
      biological systems and result in the rational design of sequence-specific DNA
      binding molecules.

PMID- 15863341
TI  - Non-peptidic alpha(v)beta3 antagonists containing indol-1-yl propionic acids.
AB  - We describe the synthesis and structure/activity relationship of RGD mimetics
      that are potent inhibitors of the integrin alpha(v)beta3. Indol-1-yl propionic
      acids containing a variety of basic moieties at the 5-position, as well as
      substitutions alpha and beta to the carboxy terminus were synthesized and
      evaluated. Novel compounds with improved potency have been identified.

PMID- 15863342
TI  - Aryl sulfones: a new class of gamma-secretase inhibitors.
AB  - The development of a novel series of 4-aryl, 4-phenylsulfonyl cyclohexananone
      derived gamma-secretase inhibitors for the potential treatment of Alzheimer's
      disease is described.

PMID- 15863343
TI  - Synthesis of linked berberine dimers and their remarkably enhanced DNA-binding
      affinities.
AB  - This communication describes the facile synthesis of five novel berberine dimers
      and their strong affinities toward double-stranded DNA. These berberine dimers
      were synthesized in 37-84% yields from the reaction of berberrubine with
      dihaloalkanes of varying lengths, and fully characterized by HRMS and 1H NMR.
      Compared with the monomeric parent berberine, these dimers showed greatly
      enhanced binding affinities up to approximately 100-fold, with two double helical
      oligodeoxynucleotides, d(AAGAATTCTT)2 and d(TAAGAATTCTTA)2, which was
      investigated by means of fluorescence spectrometry.

PMID- 15863344
TI  - Review of the potential of a wireless MEMS and TFT microsystems for the
      measurement of pressure in the GI tract.
AB  - Telemetry capsules have existed since the 1950s and were used to measure
      temperature, pH or pressure inside the gastrointestinal (GI) tract. It was hoped
      that these capsules would replace invasive techniques in the diagnosis of
      function disorders in the GI tract. However, problems such as signal loss and
      uncertainty of the pills position limited their use in a clinical setting. In
      this paper, a review of the capabilities of MicroElectroMechanical Systems (MEMS)
      and thick film technology (TFT) for the fabrication of a wireless pressure
      sensing microsystem is presented. The circuit requirements and methods of data
      transfer are examined. The available fabrication methods for MEMS sensors are
      also discussed and examples of wireless sensors are given. Finally the
      limitations of each technology are examined.

PMID- 15863345
TI  - Computational modelling of a total knee prosthetic loaded in a dynamic knee
      simulator.
AB  - Dynamic knee simulators attempt to reproduce the estimated forces, moments, and
      motions of both the patello-femoral and tibio-femoral joints during ambulatory
      activities. As a continuation of work designed to reproduce desired three
      dimensional joint loading and motion on a dynamic knee simulator, the goal of
      this study was to develop a computational model of a prosthetic knee placed
      within an existing computational model of a dynamic knee simulator. The resulting
      model was then used to produce inputs to the controllable axes of the simulator
      for reproduction of desired knee loading and motion. Previously, a three
      dimensional computational model of the simulator was developed and verified using
      a simplified and instrumented analog knee. The work presented here replaced the
      simplified and constrained geometries of the analog knee with structures
      representing a prosthetic knee. Three-dimensional geometries were determined
      based on digitized surface points of a right total knee replacement. Deformable
      contacts between the articulating surfaces of the tibio-femoral and patello
      femoral joints were then defined and model sensitivities were identified.
      Predicted results from the computational model were compared to experimental
      results for force profiles applied at the simulator's controllable axes. Within
      identified limitations, the model was then used to generate inputs to the
      simulator to reproduce desired patellar tendon load during a squat and desired
      out-of-sagittal-plane motion during a squat.

PMID- 15863346
TI  - Blood flow and structure interactions in a stented abdominal aortic aneurysm
      model.
AB  - Since the introduction of endovascular techniques in the early 1990s for the
      treatment of abdominal aortic aneurysms (AAAs), the insertion of an endovascular
      graft (EVG) into the affected artery segment has been greatly successful for a
      certain group of AAA patients and is continuously evolving. However, although
      minimally invasive endovascular aneurysm repair (EVAR) is very attractive, post
      operative complications may occur. Typically, they are the result of excessive
      fluid-structure interaction dynamics, possibly leading to EVG migration.
      Considering a 3D stented AAA, a coupled fluid flow and solid mechanics solver was
      employed to simulate and analyze the interactive dynamics, i.e., pulsatile blood
      flow in the EVG lumen, pressure levels in the stagnant blood filling the AAA
      cavity, as well as stresses and displacements in the EVG and AAA walls. The
      validated numerical results show that a securely placed EVG shields the diseased
      AAA wall from the pulsatile blood pressure and hence keeps the maximum wall
      stress 20 times below the wall stress value in the non-stented AAA. The sac
      pressure is reduced significantly but remains non-zero and transient, caused by
      the complex fluid-structure interactions between luminal blood flow, EVG wall,
      stagnant sac blood, and aneurysm wall. The time-varying drag force on the EVG
      exerted by physiological blood flow is unavoidable, where for patients with
      severe hypertension the risk of EVG migration is very high.

PMID- 15863347
TI  - A universal algorithm for an improved finite element mesh generation Mesh quality
      assessment in comparison to former automated mesh-generators and an analytic
      model.
AB  - The FE-modeling of complex anatomical structures is not solved satisfyingly so
      far. Voxel-based as opposed to contour-based algorithms allow an automated mesh
      generation based on the image data. Nonetheless their geometric precision is
      limited. We developed an automated mesh-generator that combines the advantages of
      voxel-based generation with improved representation of the geometry by
      displacement of nodes on the object-surface. Models of an artificial 3D-pipe
      section and a skullbase were generated with different mesh-densities using the
      newly developed geometric, unsmoothed and smoothed voxel generators. Compared to
      the analytic calculation of the 3D-pipe-section model the normalized RMS error of
      the surface stress was 0.173-0.647 for the unsmoothed voxel models, 0.111-0.616
      for the smoothed voxel models with small volume error and 0.126-0.273 for the
      geometric models. The highest element-energy error as a criterion for the mesh
      quality was 2.61x10(-2) N mm, 2.46x10(-2) N mm and 1.81x10(-2) N mm for
      unsmoothed, smoothed and geometric voxel models, respectively. The geometric
      model of the 3D-skullbase resulted in the lowest element-energy error and volume
      error. This algorithm also allowed the best representation of anatomical details.
      The presented geometric mesh-generator is universally applicable and allows an
      automated and accurate modeling by combining the advantages of the voxel
      technique and of improved surface-modeling.

PMID- 15863348
TI  - The kinematics and intra- and inter-therapist consistencies of lower cervical
      rotational manipulation.
AB  - The aim of this study was to determine the in vivo kinematics of cervical
      rotational manipulation in normal subjects and examine the consistency of this
      technique within and between therapists. A four camera motion analysis system
      operating at 120 Hz was used to measure the head on trunk angular displacements
      during manipulation performed by three therapists on eight subjects. One of the
      therapists performed the manipulation twice for each subject over separate
      sessions. A consistent pattern of de-rotation prior to thrust was found with
      little motion other than axial rotation during de-rotation and thrust. The pooled
      mean de-rotation displacement was 4.8 degrees and the pooled mean thrust angle
      was 11.3 degrees , but these varied widely, and none of the kinematic parameters
      recorded proved to be consistent within or between therapists. Most of the
      kinematic parameters were correlated with the exception of thrust duration.
      Qualitative analysis shows a consistent technique in cervical rotational
      manipulation. Pre-manipulation positioning of the head relative to the trunk was
      fairly consistent for a single therapist over separate sessions, but other than
      this, the kinematic parameters in cervical rotational manipulation are generally
      inconsistent within and between therapists.

PMID- 15863349
TI  - Classification of motor commands using a modified self-organising feature map.
AB  - In this paper, a control system for an advanced prosthesis is proposed and has
      been investigated in two different biological systems: (1) the spinal withdrawal
      reflex system of a rat and (2) voluntary movements in two human males: one normal
      subject and one subject with a traumatic hand amputation. The small-animal system
      was used as a model system to test different processing methods for the
      prosthetic control system. The best methods were then validated in the human set
      up. The recorded EMGs were classified using different ANN algorithms, and it was
      found that a modified self-organising feature map (SOFM) composed of a
      combination of a Kohonen network and the conscience mechanism algorithm (KNC) was
      superior in performance to the reference networks (e.g. multi-layer perceptrons)
      as regards training time, low memory consumption, and simplicity in finding
      optimal training parameters and architecture. The KNC network classified both
      experimental set-ups with high accuracy, including five movements for the animal
      set-up and seven for the human set-up.

PMID- 15863350
TI  - Automated analysis of MR image of hip: geometrical evaluation of the Legg-Calve
      Perthes disease.
AB  - This study proposes semi-automatic determination of geometrical features in hip
      magnetic resonance (MR) images in order to evaluate the Legg-Calve-Perthes
      disease (LCPD). Nine anatomical points on a hip image are selected by a
      clinician; then eight geometrical indexes of the hip joint are calculated:
      acetabulum head index (AHI), Wiberg angle (VCE), inner acetabular coverage angle
      (VCI), acetabular inclination angle (HTE), femoral shaft-neck angle (CC'D),
      circularity (C), convex deficiency factor (CDF) and pillar height deficiency
      factor (HDF) for the head region. The geometrical parameters are evaluated on 46
      hip images of young patients with unilateral LCPD: 23 images concern the affected
      hip and 23 the unaffected hip. The extraction of the region of interest is done
      with a seeded region growing method. All the data were centered and reduced, and
      were subjected to principal component analysis. Supervised classification is
      applied with discriminant analysis and k-nearest neighbours classification. The
      AHI appears to be the best discriminant attribute (maximum between-class variance
      ratio). Cross-validation tests indicate that we can at most reduce the parameters
      to five (AHI, CC'D, DHF, DCF and VCE). The classification error rate for the
      linear discriminant method is 12.5%.

PMID- 15863351
TI  - Expansion anchors for use in anterior cruciate ligament (ACL) reconstruction:
      establishing proof of concept in a benchtop analysis.
AB  - The current method for graft fixation in bone tendon-bone anterior cruciate
      ligament (ACL) reconstruction is the interference screw. Although this method of
      fixation provides for adequate graft fixation with respect to strength,
      intraoperative placement is difficult and the failure rate is high. To address
      these concerns, we have designed and fabricated prototype expansion anchors that
      could be expanded to anchor the graft in the bone tunnel. As a first step in
      assessing the validity of this concept, in the current work, we demonstrate that
      these systems are of comparable fixation strength (biomechanical pullout testing)
      to the standard interference screw, are smaller at the time of insertion and thus
      provide for increased visibility and ease of placement. The increased visibility
      should result in better placement and reduced failure rates. The increased ease
      of placement should result in significant savings in decreased OR time.

PMID- 15863352
TI  - Effects of pre-cooling and pre-heating procedures on cement polymerisation and
      thermal osteonecrosis in cemented hip replacements [Medical Engineering & Physics
      25 (2003) 559-64].

PMID- 15863354
TI  - Effects of three novel metalloproteinases from the venom of the West African saw
      scaled viper, Echis ocellatus on blood coagulation and platelets.
AB  - Two metalloproteinases, a 24-kDa P-I EoVMP1 and a 56-kDa P-III EoVMP2, have
      recently been isolated from the venom of the West African saw-scaled viper Echis
      ocellatus. We now reveal a new 65-kDa haemorrhagic group P-III metalloproteinase
      which we have designated EoVMP3. The aim of this study was to determine whether
      these three snake venom metalloproteinases (SVMPs) affect platelets and blood
      coagulation. EoVMP1 had no effect on the aggregation of washed human platelets,
      whereas EoVMP2 inhibited collagen-induced platelet aggregation. In contrast,
      EoVMP3 did not inhibit the aggregation of platelets by collagen but instead
      activated platelets in the absence of any additional co-factors. All three SVMPs
      were capable of activating prothrombin to varying degrees and can therefore be
      described as procoagulants. EoVMP1, EoVMP2 and EoVMP3 share sequence identity
      with other members of the reprolysin family, but differ greatly in their effects
      on some of the components that control haemostasis.

PMID- 15863355
TI  - Glycosylation of site-specific glycans of alpha1-acid glycoprotein and
      alterations in acute and chronic inflammation.
AB  - BACKGROUND: alpha(1)-Acid glycoprotein (AGP), an acute phase reactant, is
      extensively glycosylated at five Asn-linked glycosylation sites. In a number of
      pathophysiological states, including inflammation, rheumatoid arthritis, and
      cancer, alterations of Asn-linked glycans (N-glycans) have been reported. We
      investigated alteration of N-glycans at each of glycosylation sites of AGP in the
      sera of patients with acute and chronic inflammation. METHODS: AGP purified from
      sera was digested with Glu-C and the liberated glycopeptides were isolated by
      reverse phase HPLC. N-glycans released with peptide N-glycosidase F and followed
      by neuraminidase treatment were analyzed by matrix-assisted laser desorption
      ionization-time of flight mass spectrometry. RESULTS: Site-specific differences
      in branching structures were observed among N-glycosylation sites 1, 3, 4 and 5.
      Within the sera of patients with acute inflammation, increases in bi-antennary
      and decreases in tri- and tetra-antennary structures were observed, as well as
      increases in alpha1,3-fucosylation, at most glycosylation sites. In the sera of
      patients with chronic inflammation, increased rates of tri-antennary alpha1,3
      fucosylation at sites 3 and 4 and tetra-antennary alpha1,3-fucosylation at sites
      3, 4 and 5 were detected. Although there were no significant differences between
      acute and chronic sera in site directed branching structures, significant
      differences of alpha1,3-fucosylation were detected in tri-antennary at sites 2, 4
      and 5 and in tetra-antennary at sites 3 and 4. CONCLUSION: Little variation in
      the N-glycan composition of the glycosylation sites of AGP was observed among
      healthy individuals, while the sera of patients with acute inflammation
      demonstrated increased numbers of bi-antennary and alpha1,3-fucosylated N-glycan
      structures at each glycosylation site.

PMID- 15863356
TI  - The association of different urinary proteins with calcium oxalate hydromorphs.
      Evidence for non-specific interactions.
AB  - It has been proposed that various urinary proteins interact specifically with
      different calcium oxalate hydromorphs and these interactions have important
      implications regarding the understanding of the onset and progress of kidney
      stone disease. Calcium oxalate monohydrate and dihydrate crystals were grown and
      characterised thoroughly to establish sample purity. These crystals were then
      incubated in artificial urine samples containing isolated urinary macromolecules.
      Crystal growth was prevented by saturating the incubation mix with calcium
      oxalate, and this was confirmed through electron microscopy and calcium
      measurements of the incubation mix. The surface interactions between the
      different calcium oxalate hydrates and urinary proteins were investigated by the
      use of Western blots and immunoassays. The same proteins, notably albumin, Tamm
      Horsfall protein, osteopontin and prothrombin fragment 1, associated with both
      hydrates. There was a trend for more protein to associate with calcium oxalate
      dihydrate, and greater quantities of different proteins associated with both
      hydrates when Tamm-Horsfall protein was removed from the incubation mix. There is
      no evidence from this study to indicate that particular proteins interact with
      specific calcium oxalate hydrates, which in turn suggests that these protein
      mineral interactions are likely to be mediated through non-specific charge
      interactions.

PMID- 15863357
TI  - Sphingosine kinase 1 is involved in dibutyryl cyclic AMP-induced granulocytic
      differentiation through the upregulation of extracellular signal-regulated
      kinase, but not p38 MAP kinase, in HL60 cells.
AB  - The role of sphingosine kinase (SPHK) in the dibutyryl cyclic AMP (dbcAMP)
      induced granulocytic differentiation of HL60 cells was investigated. During
      differentiation, SPHK activity was increased, as were mRNA and protein levels of
      SPHK1, but not of SPHK2. Pretreatment of HL60 cells with N,N-dimethylsphingosine
      (DMS), a potent SPHK inhibitor, completely blocked dbcAMP-induced
      differentiation. The phosphorylation of mitogen-activated protein kinases
      (MAPKs), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK was
      also increased during dbcAMP-induced differentiation. Pretreatment of HL60 cells
      with the MEK inhibitor, U0126, but not the p38 MAPK inhibitor, SB203580,
      completely suppressed dbcAMP-induced ERK1/2 activation and granulocytic
      differentiation, but did not affect the increase in SPHK activity. DMS inhibited
      dbcAMP-induced ERK1/2 activation, but had little effect on p38 MAPK activation.
      DMS had no effect on the dbcAMP-induced membrane translocation of protein kinase
      C (PKC) isozymes, and PKC inhibitors had no significant effect on ERK activation.
      The overexpression of wild-type SPHK1, but not dominant negative SPHK1, resulted
      in high basal levels of ERK1/2 phosphorylation and stimulated granulocytic
      differentiation in HL60 cells. These data show that SPHK1 participates in the
      dbcAMP-induced differentiation of HL60 cells by activating the MEK/ERK pathway.

PMID- 15863358
TI  - Detection of the steroidogenic acute regulatory protein, StAR, in human liver
      cells.
AB  - Overexpressing StAR (a mitochondrial cholesterol transporter) increases (>5-fold)
      the rate of 27-hydroxylation of cholesterol and the rates of bile acid synthesis
      in primary rat hepatocytes; suggesting that the transport of cholesterol into
      mitochondria is rate-limiting for bile acid biosynthesis via the CYP27A1
      initiated 'acidic' pathway. Our objective was to determine the level of StAR
      expression in human liver and whether changes in StAR would correlate with
      changes in CYP27A1 activity/bile acid synthesis rates in human liver tissues.
      StAR mRNA and protein were detected in primary human hepatocytes and HepG2 cells
      by RT-PCR/Northern analysis and by Western analysis, respectively. In
      immunocompetition assays, liver StAR was competed away with the addition of
      purified human adrenal StAR. Overexpressing CYP27A1 in both cell types led to >2
      fold increases in liver StAR concentration. StAR protein levels also increased
      approximately 2-fold with the addition of 27-hydroxycholesterol to HepG2 cell
      culture medium. Overexpressing StAR increased the rates of 27-hydroxylation of
      cholesterol/bile acid synthesis in both cell lines and increased intracellular
      levels of 27-hydroxycholesterol. In conclusion, human liver cells contain
      regulable StAR protein whose level of expression appears capable of regulating
      cellular cholesterol homeostasis, representing a potential therapeutic target in
      the management of hyperlipidemia.

PMID- 15863359
TI  - Stress-induced platelet-activating factor synthesis in human neutrophils.
AB  - Platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine; PAF)
      is a potent inflammatory mediator produced by cells in response to physical or
      chemical stress. The mechanisms linking cell injury to PAF synthesis are unknown.
      We used liquid chromatography-tandem mass spectrometry to investigate stress
      induced PAF synthesis in human neutrophils. PAF synthesis induced by
      extracellular pH 5.4 correlated with the activation of a stress-activated kinase,
      p38 mitogen-activated protein kinase (MAPK), and was blocked by the p38 MAPK
      inhibitor SB 203580. A key enzyme of PAF synthesis, acetyl-CoA:lysoPAF
      acetyltransferase, which we have previously shown is a target of p38 MAPK, was
      also activated in an SB 203580-sensitive fashion. Another MAPK pathway,
      extracellular signal-regulated kinase-1/2 (ERK-1/2), was also activated.
      Surprisingly, the pharmacological blockade of the ERK-1/2 pathway with PD 98059
      did not block, but rather enhanced, PAF accumulation. Two unexpected actions of
      PD 98059 may underlie this phenomenon: an augmentation of stress-induced p38 MAPK
      phosphorylation and an inhibition of PAF catabolism. The latter effect did not
      appear to be due to a direct inhibition of PAF acetylhydrolase. Finally, similar
      results were obtained using another form of cellular stress, hypertonic sodium
      chloride. These data are consistent with a model in which stress-induced PAF
      accumulation is regulated positively by p38 MAPK and negatively by ERK-1/2. Such
      a model contrasts with the PAF accumulation induced by other forms of
      stimulation, which we and others have found is up-regulated by both p38 MAPK and
      ERK-1/2.

PMID- 15863360
TI  - Diversity of SREBP-1 gene expression in rat adipose tissue depots in response to
      refeeding after food restriction.
AB  - The SREBP-1c mRNA level and precursor (microsomal) form of SREBP-1 abundance were
      significantly higher in epididymal and perirenal than in subcutaneous white
      adipose tissue of control rats. Moreover, the SREBP-1c mRNA level and an amount
      of precursor form of SREBP-1 were significantly higher in the epididymal and
      perirenal white adipose tissue of rats maintained on restricted diet and refed ad
      libitum for 48 h as compared to the control animals. No significant effects of
      food restriction/refeeding on SREBP-1c mRNA level and an amount of precursor form
      of SREBP-1 were found in subcutaneous white adipose tissue. The mature (nuclear)
      form of SREBP-1 was significantly increased in the epididymal, perirenal and
      subcutaneous white adipose tissue of the food restricted/refed animals. The
      activity, protein level and the mRNA abundance of malic enzyme (one of the target
      genes for SREBP-1) increased significantly in the epididymal, perirenal and
      subcutaneous white adipose tissue of the food restricted/refed rats as compared
      to the control animals, however the increase in perirenal and epididymal was
      higher than in the subcutaneous white adipose tissue. The results presented
      suggest that SREBP-1c is differently expressed in various rat white adipose
      tissue depots both under basal (control) and dieting conditions.

PMID- 15863361
TI  - Gene expression profile of isolated rat adipocytes treated with anthocyanins.
AB  - Adipocyte dysfunction is strongly associated with the development of obesity and
      insulin resistance. It is accepted that the regulation of adipocytokine secretion
      or the adipocyte specific gene expression is one of the most important targets
      for the prevention of obesity and amelioration of insulin sensitivity. Recently,
      we demonstrated that anthocyanins, which are pigments widespread in the plant
      kingdom, have the potency of anti-obesity in mice and the enhancement
      adipocytokine secretion and adipocyte gene expression in adipocytes. In this
      study, we have shown for the first time the gene expression profile in isolated
      rat adipocytes treated with anthocyanins (cyanidin 3-glucoside; C3G or cyanidin;
      Cy). The rat adipocytes were treated with 100 muM C3G, Cy or vehicle for 24 h.
      The total RNA from the adipocytes was isolated and carried out GeneChip
      microarray analysis. A total of 633 or 427 genes was up-regulated (>1.5-fold) by
      the treatment of adipocytes with C3G or Cy, respectively. The up-regulated genes
      include lipid metabolism and signal transduction-related genes, however, the
      altered genes were partly different between the C3G- and Cy-treated groups. Based
      on the gene expression profile, we demonstrated the up-regulation of hormone
      sensitive lipase and enhancement of the lipolytic activity by the treatment of
      adipocytes with C3G or Cy. These data have provided an overview of the gene
      expression profiles in adipocytes treated with anthocyanins and identified new
      responsive genes with potentially important functions in adipocytes related with
      obesity and diabetes that merit further investigation.

PMID- 15863362
TI  - Nuclear phospholipase C-beta1b activation during G2/M and late G1 phase in
      nocodazole-synchronized HL-60 cells.
AB  - In this study, the activity of nuclear phosphatidylinositol-specific phosholipase
      C (PI-PLC) was investigated in HL-60 cells blocked at G(2)/M phase by the
      addition of nocodazole, and released into medium as synchronously progressing
      cells. Two peaks of an increase in the nuclear PI-PLC activities were detected;
      an early peak reached a maximum at 1 h after release from the nocodazole block,
      and a second increase was detected at 8.5 h after the release.
      Immunoprecipitation studies indicated that the increase in the activity was due
      to the activation of the nuclear PI-PLC-beta(1). Western blot analysis
      demonstrated no changes in the level of both a and b splicing variants of PI-PLC
      beta(1) in the nuclei of cells isolated at either 1 h or 8.5 h after the block.
      However, an increase in the serine-phosphorylation of PI-PLC-beta(1b) was
      detected in the nuclei of HL-60 cells isolated at 1 and 8.5 h after the block,
      and the presence of MEK-inhibitor PD98059 completely inhibited both the serine
      phosphorylation and the increase in the PI-PLC activities in vitro. The presence
      of PI-PLC inhibitor prevented the progression of HL-60 cells through the G(1)
      into S phase of the cell cycle. These results demonstrate that two peaks of
      nuclear PI-PLC activities, which are due to a PD98059-sensitive phosphorylation
      of nuclear PLC-beta(1b) on serine, occur at the G(2)/M and late G(1) phase and
      are necessary for the progression of the cells through the cell cycle.

PMID- 15863363
TI  - Statins potentiate the IFN-gamma-induced upregulation of group IIA phospholipase
      A2 in human aortic smooth muscle cells and HepG2 hepatoma cells.
AB  - The present study shows that the incubation of human aortic smooth muscle cells
      (HASMC) and HepG2 cells with atorvastatin and mevastatin as HMG-CoA reductase
      inhibitors potentiated the interferon-gamma (INF-gamma)-induced group IIA
      phospholipase A(2) (sPLA(2)-IIA) expression in a dose- and time-dependent manner.
      The effect of statins on sPLA(2)-IIA expression was reduced by mevalonate,
      farnesyl pyrophosphate and geranylgeranyl pyrophosphate. Inversely, inhibitors of
      the farnesyl transferase and geranylgeranyl transferase-I mimicked the effects of
      statins. Clostridium difficile toxin B (TcdB), Y-27632 and H-1152, functioning as
      inhibitors of Rho proteins and Rho-associated kinase, also augmented the sPLA(2)
      IIA expression in combination with IFN-gamma. The same effects were observed when
      inhibitors of mitogen-activated/extracellular response protein kinase kinase
      (MEK), PD98059 or U0126 were used. Further, the Janus kinase-2 (Jak2)-specific
      inhibitor, AG-490 and inhibitors of nuclear factor-kappaB (NFkappaB) abrogated
      the sPLA(2)-IIA elevating effects of statins, TcdB and PD98059 in the presence of
      IFN-gamma. This cytokine alone increased the NFkappaB p65 and CAAT-enhancer
      binding protein-beta (C/EBP-beta) activity in HASMC nuclear extract, but only
      C/EBP-beta was further augmented when the cells were incubated in addition to IFN
      gamma with atorvastatin, H-1152, PD98059 or U0126. Moreover, after the incubation
      of cells with atorvastatin and IFN-gamma the stability of sPLA-(2)IIA mRNA
      significantly increased in comparison to those after incubation with IFN-gamma
      alone. In conclusion, the obtained data suggest that (i) the expression of
      sPLA(2)-IIA is negatively regulated by RhoA/Rho-associated kinase and MEK/ERK
      signaling pathways and (ii) statins, because of their ability to down-regulate
      these pathways, can potentiate the IFN-gamma-induced sPLA(2)-II expression at
      transcriptional and post-transcriptional levels.

PMID- 15863364
TI  - MAPKs mediate the activation of cytosolic phospholipase A2 by amyloid beta(25-35)
      peptide in bovine retina pericytes.
AB  - We have previously shown that, in bovine retina pericytes, amyloid beta(1-42) and
      its truncated form containing amino acids 25-35, after 24 h treatment, stimulate
      arachidonic acid (AA) release and phosphatidylcholine hydrolysis, by activation
      of both cytosolic (cPLA(2)) and Ca(2+)-independent (iPLA(2)) phospholipase A(2).
      A putative role for MAP kinases in this process emerged. Here we studied the role
      of the MAP-kinase family as well as both cPLA(2) and iPLA(2) mRNA expression by a
      semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in the
      same sublethal model of amyloid-beta (Abeta) damage to pericytes in vitro.
      Abeta(25-35) peptide evoked AA release as well as stimulated phosphorylation of
      ERK1/2, p38 MAPKs and cPLA(2), but not c-Jun N-terminal kinase (JNK/SAPK).
      PD98059, an inhibitor of ERK-activating kinase MEK-1, and SB203580, an inhibitor
      of p38 protein kinase, abolished the stimulation of AA release and MAPK
      activities. In cells stimulated by Abeta(25-35) peptide, Western blotting and
      confocal microscopy analyses confirmed either an increase in the phosphorylated
      form of ERKs and p38 or their nuclear translocation. A complete inhibition of
      MAPK activation and AA release was also observed when pericytes were treated with
      GF109203X, a general PKC inhibitor, indicating the important role of both PKC and
      the two MAPKs in mediating the Abeta peptide response. Compared with samples
      untreated or treated with reverse Abeta(35-25) peptide, pretreatment with 50
      microM Abeta(25-35) for 24 h significantly increased the level of constitutively
      expressed iPLA(2) mRNA by 25%, which seems to depend on the activation of
      kinases. By contrast, the level of cPLA(2) mRNA remained unchanged. Together,
      these data link either the stimulation of PKC-ERK-p38 cascades or PLA(2) activity
      by Abeta peptide to prooxidant mechanism induced by amyloid, which may initially
      stimulate the cell reaction as well as metabolic repair, such as during
      inflammation.

PMID- 15863365
TI  - Anti-inflammatory effects of phospholipid transfer protein (PLTP) deficiency in
      mice.
AB  - We previously reported that phospholipid transfer protein-deficient (PLTP KO)
      mice exhibit a lower rate of atherosclerosis. We proposed two possible
      mechanisms: a reduction in hepatic apoB secretion (Nat Med 7 (2001) 847) and
      induction of lipoprotein anti-oxidation activity (J Biol Chem 277 (2002) 31850).
      We now hypothesized that PLTP KO mice may exhibit an anti-inflammatory state per
      se. First, we found that PLTP KO mice have significantly lower IL-6 levels than
      wild type (WT) mice. Secondly, we found that IL-6 treatment increased plasma
      TNFalpha levels in WT mice, but not in PLTP KO mice. Thirdly, we used flow
      cytometric analyses to measure the mean fluorescence intensity of I-A(b), a MHC
      class II molecule, on peripheral monocytes and found that IL-6 treatment
      significantly increased the I-A(b)-positive cell levels in WT mice, whereas no
      changes were observed in the cell levels in PLTP KO mice. The results of our
      experiments demonstrated an anti-inflammatory effect of PLTP deficiency as a
      further aspect of its proatherogenic potency.

PMID- 15863366
TI  - Turpentine-induced inflammation reduces the hepatic expression of the multiple
      drug resistance gene, the plasma cholesterol concentration and the development of
      atherosclerosis in apolipoprotein E deficient mice.
AB  - We aimed to investigate the effect of turpentine-induced inflammation in an
      atherosclerosis-prone murine model. We have induced a chronic aseptic
      inflammation in apolipoprotein E-deficient mice, with or without a dietary
      supplement of aspirin (n = 10, each), by the injection of a mixture (1:1) of
      turpentine and olive oil in the hind limb twice weekly for a period of 12 weeks.
      Control animals were injected with olive oil alone (n = 10). The control mice did
      show any alteration neither in plasma nor at the site of injection. Turpentine
      treated mice showed a significant increase in plasma TNF-alpha and SAA
      concentrations which indicated a systemic inflammatory response that was not
      substantially affected by aspirin. Also, turpentine injections significantly
      reduced the plasma cholesterol concentration, probably decreasing intestinal
      cholesterol re-absorption, and attenuated the size of atherosclerotic lesion.
      Both effects were minimally influenced by aspirin. The burden of atherosclerosis
      correlated with plasma lipid levels but not with plasma inflammatory markers.
      Finally, there was a concomitant decrease in the expression of the hepatic mdr1b
      gene that correlated with the decrease in plasma cholesterol concentration.
      Therefore, we conclude that mdr1 is an additional factor to consider in the
      complexity of alterations in cholesterol metabolism that occur in this model.

PMID- 15863367
TI  - The phospholipid scramblase PLSCR1 increases UV induced apoptosis primarily
      through the augmentation of the intrinsic apoptotic pathway and independent of
      direct phosphorylation by protein kinase C delta.
AB  - Cell death by apoptosis can be caused by the DNA mutagen UV light whose exposure
      causes the direct activation of both the caspase 9 regulated cell damage
      intrinsic pathway and the caspase 8 regulated plasma membrane extrinsic pathway.
      We determined that increased activity of the plasma membrane phospholipid
      scramblase, PLSCR1, amplified UV mediated apoptosis primarily through the
      activation of the intrinsic apoptotic pathway. The caspase 8 inhibitor z-IETD-fmk
      was not as effective an inhibitor of PLSCR1 augmented UV induced apoptosis
      compared to treatment with caspase 3, caspase 9, or pan-caspase inhibitors. The
      inability of the caspase 8 inhibitor to decrease UV induced apoptosis was
      dependent on PLSCR1, as UV induced apoptosis was decreased by a similar amount in
      the control cells in the presence of inhibitors of caspase 8, caspase 9, caspase
      3, or the pan-caspase inhibitor. PKC-delta directly phosphorylates human PLSCR1
      resulting in increased PLSCR1 scramblase activity. PKC-delta can also be
      activated by caspase mediated cleavage resulting in the release of a
      constitutively active kinase domain. We observed that replacing the PKC-delta
      phosphorylation site of PLSCR1 with an alanine did not affect the ability of
      PLSCR1 to enhance UV induced apoptosis implying that PKC-delta does not directly
      phosphorylate PLSCR1 to increase plasma membrane scramblase activity during
      apoptosis. Cells transfected with a PLSCR1 mutant that contained an alanine
      substitution at its known PKC-delta phosphorylation site underwent UV induced
      apoptosis at a level similar to those transfected with wild type PLSCR1. The
      combined results indicate that UV exposure in cells possessing PLSCR1 increases
      apoptosis primarily by enhancement of the intrinsic apoptotic pathway, and also
      imply that the increased apoptosis observed upon exposure to UV light is not
      through direct phosphorylation of PLSCR1 by PKC-delta.

PMID- 15863368
TI  - Time-resolved fluoroimmunoassays of the complete set of secreted phospholipases
      A2 in human serum.
AB  - Time-resolved fluoroimmunoassays (TR-FIA) were developed for all human secreted
      phospholipases A(2) (PLA(2)), viz. group (G) IB, GIIA, GIID, GIIE, GIIF, GIII,
      GV, GX and GXIIA PLA(2) and the GXIIB PLA(2)-like protein. Antibodies were raised
      in rabbits against recombinant human PLA(2) proteins and used in sandwich-type TR
      FIAs as both catching and detecting antibodies, the latter after labeling with
      Europium. The antibodies were non-cross-reactive. The analytical sensitivities
      were 1 microg/L for the TR-FIA for GIB PLA(2), 1 microg/L (GIIA), 35 microg/L
      (GIID), 3 microg/L (GIIE), 4 microg/L (GIIF), 14 microg/L (GIII), 11 microg/L
      (GV), 2 microg/L (GX), 92 microg/L (GXIIA) and 242 microg/L (GXIIB). All secreted
      PLA(2)s were assayed by these TR-FIAs in serum samples from 34 patients (23 men
      and 11 women, mean age 53.2 years) treated in an intensive care unit for septic
      infections, and in control samples from 28 volunteer blood donors (14 men and 14
      women, mean age 57.0 years). Five serum samples (3 in the sepsis group and 2 in
      the blood donor group) gave high TR-FIA signals that were reduced to background
      (blank) levels by the addition of non-immune rabbit IgG to the sera. This
      reactivity was assumed to be due to the presence of heterophilic antibodies in
      these subjects. In all other subjects, including septic patients and healthy
      blood donors, the TR-FIA signals for GIID, GIIE, GIIF, GIII, GV, GX and GXIIA
      PLA(2) and the GXIIB PLA(2)-like protein were at background (blank) levels. Four
      patients in the sepsis group had pancreatic involvement and elevated
      concentration of GIB PLA(2) in serum (median 19.0 microg/L, range 13.1-33.7
      microg/L, n = 4) as compared to the healthy blood donors (median 1.8 microg/L,
      range 0.8-3.4 microg/L, n = 28, P < 0.0001). The concentration of GIIA PLA(2) in
      the sera of septic patients (median 315.7 microg/L, range 15.9-979.6 microg/L, n
      = 34) was highly elevated as compared to that of the blood donors (median 1.8
      microg/L, range 0.8-5.8 microg/L, n = 28, P < 0.0001). Our current results
      confirmed elevated concentrations of GIB and GIIA PLA(2) in the sera of patients
      suffering from acute pancreatitis or septic infections, respectively, as compared
      to healthy subjects. However, in the same serum samples, the concentrations of
      the other secreted PLA(2)s, viz. GIID, GIIE, GIIF, GIII, GV, GX and GXIIA PLA(2)
      and the GXIIB PLA(2)-like protein were below the respective analytical
      sensitivities of the TR-FIAs. It is concluded that generalized bacterial
      infections do not lead to elevated serum levels of GIIE, GIIF, GIII, GV and GX
      PLA(2)s above the detection limits of the current TR-FIAs.

PMID- 15863369
TI  - Supplementation with alpha-linolenic acid-rich diacylglycerol suppresses fatty
      liver formation accompanied by an up-regulation of beta-oxidation in Zucker fatty
      rats.
AB  - Insulin resistance-related obesity and diabetes mellitus are the predominant
      causes of fatty liver disease. Here we examine the effects of dietary
      diacylglycerol (DG), which is a minor component of plant oils, on lipid
      accumulation and the expression of genes involved in lipid metabolism in the
      liver. The animals were fed diets containing either 10% triacylglycerol (TG), 10%
      TG + 4% alpha-linolenic acid-rich TG (ALATG) or 10% TG + 4% alpha-linolenic acid
      rich diacylglycerol (ALADG) for a period of 1 month. Supplementation with ALADG
      significantly inhibited hepatic triglyceride accumulation; this was accompanied
      by the up-regulation of beta-oxidation activity, and acyl-CoA oxidase (ACO) and
      medium-chain acyl-CoA dehydrogenase (MCAD) mRNA levels. By contrast, no
      significant changes were observed in the levels of peroxisome proliferator
      activated receptor-alpha (PPARalpha) and sterol regulatory element-binding
      protein-1 (SREBP-1) mRNAs. These results indicate that ALADG might be useful in
      the prevention of fatty liver formation; this effect could be closely related to
      the stimulation of lipid catabolism in the liver. In addition, our findings
      suggest that both acylglycerol structure (that is, the structural difference
      between TG and DG) and fatty-acid species affect the nutritional behaviour of
      dietary lipids.

PMID- 15863370
TI  - The activities of monocyte lysophosphatidylcholine acyltransferase and coenzyme A
      independent transacylase are changed by the inflammatory cytokines tumor necrosis
      factor alpha and interferon gamma.
AB  - Alteration of membrane phospholipid fatty acid compositions has been shown to be
      important for leukocyte inflammatory responses. Such modification of the
      molecular species of these lipid classes requires deacylation and reacylation
      reactions and for phosphatidylcholines, lysophosphatidylcholine acyltransferase
      (LPCAT) and a coenzyme A-independent transacylase (CoAIT) can each be involved.
      Since previous studies have shown a significant IFNgamma- and TNFalpha-induced
      modification of phosphatidylcholine species, we have examined whether these
      inflammatory cytokines alter the activity of reacylation enzymes in the human
      monocyte cell line MonoMac 6 (MM6). IFN-gamma caused a significant increase in
      the activity of the LPCAT and CoAIT enzymes in the microsomal fraction at
      concentrations and over a time-course consistent with an important role for these
      enzymes in the sensitization (priming) of monocytes. In contrast, TNFalpha was
      found to significantly increase the activity of the CoAIT by 50% over controls in
      MM6 cells after 30 min incubation with the cytokine, but decreased LPCAT activity
      by 65% after 24 h incubation. Such data imply that CoAIT is important for the
      remodelling of phospholipid composition, which is seen during the acute response
      of cells to TNFalpha. The results provide further information to emphasise the
      role of acyltransferases as part of the molecular mechanism underlying
      inflammation.

PMID- 15863371
TI  - The end for genital human papillomavirus infections?

PMID- 15863372
TI  - Who will benefit from treatment against EGFR?

PMID- 15863373
TI  - Effect of dose-intensive chemotherapy on quality of life.

PMID- 15863374
TI  - Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus
      like particle vaccine in young women: a randomised double-blind placebo
      controlled multicentre phase II efficacy trial.
AB  - BACKGROUND: A randomised double-blind placebo-controlled phase II study was done
      to assess the efficacy of a prophylactic quadrivalent vaccine targeting the human
      papillomavirus (HPV) types associated with 70% of cervical cancers (types 16 and
      18) and with 90% of genital warts (types 6 and 11). METHODS: 277 young women
      (mean age 20.2 years [SD 1.7]) were randomly assigned to quadrivalent HPV (20
      microg type 6, 40 microg type 11, 40 microg type 16, and 20 microg type 18) L1
      virus-like-particle (VLP) vaccine and 275 (mean age 20.0 years [1.7]) to one of
      two placebo preparations at day 1, month 2, and month 6. For 36 months,
      participants underwent regular gynaecological examinations, cervicovaginal
      sampling for HPV DNA, testing for serum antibodies to HPV, and Pap testing. The
      primary endpoint was the combined incidence of infection with HPV 6, 11, 16, or
      18, or cervical or external genital disease (ie, persistent HPV infection, HPV
      detection at the last recorded visit, cervical intraepithelial neoplasia,
      cervical cancer, or external genital lesions caused by the HPV types in the
      vaccine). Main analyses were done per protocol. FINDINGS: Combined incidence of
      persistent infection or disease with HPV 6, 11, 16, or 18 fell by 90% (95% CI 71
      97, p<0.0001) in those assigned vaccine compared with those assigned placebo.
      INTERPRETATION: A vaccine targeting HPV types 6, 11, 16, 18 could substantially
      reduce the acquisition of infection and clinical disease caused by common HPV
      types.

PMID- 15863375
TI  - Gene copy number for epidermal growth factor receptor (EGFR) and clinical
      response to antiEGFR treatment in colorectal cancer: a cohort study.
AB  - BACKGROUND: The antiepidermal growth factor receptor (antiEGFR) monoclonal
      antibodies cetuximab and panitumumab have good clinical activity in about 10% of
      patients with metastatic colorectal cancer that is resistant to chemotherapy. The
      molecular mechanisms underlying clinical response or resistance to these agents
      are unknown. METHODS: Tumours from 31 patients with metastatic colorectal cancer
      who had either an objective response (n=10) or stable disease or progressive
      disease (n=21) after treatment with cetuximab or panitumumab were screened for
      genetic changes in EGFR or its immediate intracellular effectors. Specifically,
      we assessed the EGFR copy number and the mutation profile of the EGFR catalytic
      domain and of selected exons in KRAS, BRAF, and PIK3CA. RESULTS: Eight of nine of
      patients with objective responses who were assessable by fluorescence in-situ
      hybridisation (FISH) had an increased EGFR copy number. By contrast, one of 21
      non-responders assessable by FISH had an increased EGFR copy number (p<0.0001 for
      responders vs non-responders, Fisher's exact test). The mutation status of the
      EGFR catalytic domain and its immediate downstream effectors PIK3CA, KRAS, and
      BRAF did not correlate with disease response. In colorectal-cancer cell lines,
      the concentration of cetuximab that completely inhibited proliferation of cells
      with amplified EGFR copy number did not affect proliferation of cells with
      unamplified EGFR. INTERPRETATION: We propose that the response to antiEGFR
      treatment has a genetic basis and suggest that patients might be selected for
      treatment on the basis of EGFR copy number.

PMID- 15863376
TI  - Health-related quality of life in survivors of locally advanced breast cancer: an
      international randomised controlled phase III trial.
AB  - BACKGROUND: Dose-intensive chemotherapy has generated much interest in the
      treatment of patients with locally advanced breast cancer because it might offer
      a survival benefit. We aimed to compare the effects of such an approach with
      those of standard chemotherapy on health-related quality of life (HRQOL).
      METHODS: 224 patients with locally advanced breast cancer were randomly assigned
      to 75 mg/m(2) cyclophosphamide given orally on days 1-14, and 60 mg/m(2)
      epirubicin and 500 mg/m(2) fluorouracil both given intravenously on days 1 and 8,
      for six cycles every 28 days (6 months' treatment; standard treatment) and 224
      patients to 830 mg/m(2) cyclophosphamide and 120 mg/m(2) epirubicin both given
      intravenously on day 1, and 5 microg/kg filgrastim per day given subcutaneously
      on days 2-13, for six cycles every 14 days (3 months' treatment; dose-intensive
      treatment). HRQOL was assessed by use of the European Organisation for Research
      and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30).
      Baseline assessments were done before randomisation; then once a month for the
      first 3 months; and at months 6, 9, 12, 18, 26, 34, 42, 48, and 54. The primary
      endpoint was progression-free survival; secondary endpoints were HRQOL, response,
      safety, overall response, and health economics. Analyses were by intention to
      treat. FINDINGS: Previously reported data showed that groups did not differ in
      progression-free survival. Patients assigned shorter, intensified treatment had a
      significantly lower overall HRQOL score during the first 3 months than did those
      assigned standard treatment (mean score at 3 months 41.8 [SD 1.78] vs 49.6
      [1.64], p=0.0015). However, scores returned to near baseline, with no difference
      between groups, at 12 months (62.6 [1.97] vs 65.6 [2.04], p=0.3007). Over the
      remaining 2 years, the groups showed few significant differences in HRQOL.
      INTERPRETATION: Dose-intensive treatment only has a temporary effect on HRQOL,
      thus enabling more research on intensive treatment for patients with locally
      advanced breast cancer.

PMID- 15863377
TI  - Efficacy of tamoxifen and radiotherapy for prevention and treatment of
      gynaecomastia and breast pain caused by bicalutamide in prostate cancer: a
      randomised controlled trial.
AB  - BACKGROUND: Gynaecomastia and breast pain are frequent adverse events with
      bicalutamide monotherapy, and might cause some patients to withdraw from
      treatment. We aimed to compare tamoxifen with radiotherapy for prevention and
      treatment of gynaecomastia, breast pain, or both during bicalutamide monotherapy
      for prostate cancer. METHODS: 51 patients were randomly assigned to 150 mg
      bicalutamide per day, 50 patients to 150 mg bicalutamide per day and to 10 mg
      tamoxifen per day for 24 weeks, and 50 patients to 150 mg bicalutamide per day
      and radiotherapy (one 12-Gy fraction on the day of starting bicalutamide). 35 of
      the 51 patients allocated bicalutamide alone developed gynaecomastia or breast
      pain and were subsequently randomly allocated to tamoxifen (n=17) or radiotherapy
      (n=18) soon after symptoms started (median 180 days, range 160-195).
      Gynaecomastia and breast pain were assessed once a month. Severity of
      gynaecomastia was scored on the basis of the largest diameter. Breast pain was
      scored as none, mild, moderate, or severe. The primary outcome was frequency of
      gynaecomastia or breast pain; secondary outcomes were safety and tolerability,
      relapse-free survival, as assessed by concentration of prostate specific antigen,
      and quality of life. Analyses were by intention to treat. RESULTS: 35 of 51
      patients assigned bicalutamide alone developed gynaecomastia, compared with four
      of 50 assigned bicalutamide and tamoxifen (odds ratio [OR] 0.1 [95% CI 0.08
      0.12], p=0.0009), and with 17 of 50 assigned bicalutamide and radiotherapy (0.51
      [0.47-0.54], p=0.008). Breast pain was seen in 29 of 51 patients allocated
      bicalutamide alone, compared with three allocated bicalutamide and tamoxifen (0.1
      [0.07-0.11], p=0.009), and with 15 allocated bicalutamide and radiotherapy (0.43
      [0.40-0.45], p=0.02) In 35 patients assigned bicalutamide alone who subsequently
      developed gynaecomastia, breast pain, or both, tamoxifen significantly reduced
      the frequency of gynaecomastia (0.2 [0.18-0.22], p=0.02). INTERPRETATION:
      Antioestrogen treatment with tamoxifen could help patients with prostate cancer
      to tolerate the hypergonadotropic effects of bicalutamide monotherapy.

PMID- 15863378
TI  - Controversies and ethical issues in cancer-genetics clinics.
AB  - Genetic testing is a powerful technology that enables prediction of future health
      status. Testing for cancer-predisposition genes provides information for both the
      individual and his or her family. The use of this information reaches beyond the
      medical sphere to the psychological, social, legal, and ethical. The important
      issues include informed consent, autonomy, confidentiality, justice, disclosure
      and non-disclosure, duty to warn, genetic discrimination, predictive genetic
      testing of children, preimplantation genetic diagnosis, and patenting of cancer
      predisposition genes.

PMID- 15863379
TI  - Endoscopic treatment of high-grade dysplasia and early cancer in Barrett's
      oesophagus.
AB  - Barrett's oesophagus is the premalignant precursor of oesophageal adenocarcinoma.
      Non-dysplastic metaplasia can progress to low-grade dysplasia, high-grade
      dysplasia, and finally to invasive cancer. Although the frequency of
      adenocarcinoma in patients with Barrett's oesophagus is low, surveillance is
      justified because the outcome of adenocarcinoma is poor. Oesophagectomy remains
      the standard treatment for patients with high-grade dysplasia and superficial
      carcinoma. However, it has been associated with substantial morbidity and
      mortality and some patients are judged unfit for surgery. In this review, the
      present status of less invasive procedures is discussed. Endotherapy preserves
      the integrity of the oesophagus and allows a better quality of life to patients
      at low risk of developing lymph-node metastases. Opposition to endoscopic
      treatment is based mainly on the identification of undetected foci of cancer and
      high-grade dysplasia in oesophagectomy samples. The current ablative techniques
      used are photodynamic therapy, argon plasma coagulation, laser treatment, and
      endoscopic mucosal resection.

PMID- 15863380
TI  - The MAPK signalling pathways and colorectal cancer.
AB  - There are three major subfamilies of mitogen-activated protein kinases (MAPK):
      the extracellular-signal-regulated kinases (ERK MAPK); the c-jun N-terminal
      kinase or stress-activated protein kinases (JNK or SAPK); and MAPK14. The ERK
      MAPK pathway is one of the most important for cell proliferation. The MAPK
      pathways are located downstream of many growth-factor receptors, including that
      for epidermal growth factor. Overexpression and activation of this receptor are
      commonly detected in colorectal cancer, and several lines of evidence indicate
      that overexpression and activation of ERK MAPK play an important part in
      progression of this cancer. ERK MAPK could be a molecular target for treatment of
      the disorder. This review focuses on the ERK MAPK signal-transduction pathway,
      the consequences of its dysregulation in colorectal cancer, and its potential as
      an approach to cancer treatment. Future challenges for the assessment of these
      targeted agents in the clinic are also presented.

PMID- 15863381
TI  - Radiotherapy during pregnancy: fact and fiction.
AB  - Radiotherapy during pregnancy might cause harm to the developing fetus.
      Generally, pregnant women with malignant diseases are advised to delay
      radiotherapy until after delivery. However, this advice is not based on knowledge
      of the risks of radiation to the unborn child. In general, the expected radiation
      effects, such as mental retardation and organ malformations probably only arise
      above a threshold dose of 0.1-0.2 Gy. This threshold dose is not generally
      reached with curative radiotherapy during pregnancy, provided that tumours are
      located sufficiently far from the fetus and that precautions have been taken to
      protect the unborn child against leakage radiation and collimator scatter of the
      teletherapy machine; such precautions also reduce the risk of radiation-induced
      childhood cancer and leukaemia in the unborn child.

PMID- 15863382
TI  - Importance of nutritional screening in treatment of cancer-related weight loss.
AB  - Weight loss is common in patients with cancer. Many factors, such as
      physiological abnormalities, response to the tumour, and treatment, contribute to
      this weight loss. Cancer-related weight loss affects a patient's response to
      treatment, as well as survival and quality of life. Several nutritional screening
      and assessment tools have been developed for patients with cancer. This review
      describes the weight loss seen in patients with cancer as well as the methods of
      screening for nutritional deterioration and weight loss early in a cancer
      diagnosis. Nutritional approaches to the supportive care of patients with cancer
      are also discussed.

PMID- 15863383
TI  - Treatment of Epstein-Barr-virus-associated primary CNS B cell lymphoma with
      allogeneic T-cell immunotherapy and stem-cell transplantation.

PMID- 15863384
TI  - Syncope due to nasopharyngeal carcinoma.

PMID- 15863385
TI  - Retroperitoneal parachordoma in a patient with a history of recurrent pain.

PMID- 15863386
TI  - Contribution of Irf-1 promoter polymorphisms to the Th1-type cell response and
      interferon-beta monotherapy for chronic hepatitis C.
AB  - We recently reported promoter polymorphisms in the IRF-1 gene, an interferon
      inducible gene that plays an important role in host antiviral function. The
      promoter activity was shown to be different between different polymorphisms. In
      this study, we investigated the relationship between IRF-1 promoter polymorphisms
      and the response to interferon monotherapy for chronic hepatitis C. Eighteen
      patients with a low initial viral load or hepatitis C virus (HCV) genotype non-1b
      received 6-months course of interferon-beta monotherapy. IRF-1 gene mutations and
      the treatment response were investigated. The IRF-1 promoter type possessing a
      higher promoter activity (-415C/-410A/-300A) was found in only three patients,
      all of which had a lower viral load than those with other promoter types and were
      able to obtain a sustained viral response. Flow cytometric analysis of peripheral
      blood mononuclear cells showed that the patients with a higher promoter activity
      of the IRF-1 had a significantly higher proportion of T helper 1-type CD4(+)
      cells after interferon administration than those of other promoter types. These
      results suggest that IRF-1 promoter polymorphisms may contribute, at least
      partially, to host antiviral activity for chronic hepatitis C.

PMID- 15863387
TI  - Human interleukin-1 alpha gene expression is regulated by Sp1 and a
      transcriptional repressor.
AB  - The regulation of the human IL-1alpha gene was studied using a series of 5'
      deletion promoter chloramphenicol acetyltransferase (CAT) reporter constructs.
      The IL-1alpha promoter from -967 to +64 produced no significant expression of
      CAT. Progressive 5' deletion indicated the presence of a repressor binding site
      between -477 and -305 bp as deletion in this region resulted in CAT expression.
      Electrophoretic mobility shift assay (EMSA) analysis confirmed that protein(s)
      bound to this region and DNaseI footprinting localized the binding site to
      between -448 and -435. Deletion of the IL-1alpha promoter to -42 resulted in
      reduced CAT expression suggesting the presence of a positive regulatory element
      in this region. EMSA experiments using IL-1alpha promoter DNA from -163 to +64
      demonstrated protein binding to this region and DNaseI footprinting demonstrated
      protection between -59 and -40. Transcriptional activity of the IL-1alpha
      promoter was also tested using an in vitro transcription assay. Reactions using 
      163, -100 and -52 promoter templates all produced a correctly sized transcript
      but deletion to -42 resulted in no transcript production. Analysis of the
      promoter indicated that a potential Sp1 binding site existed in the region from 
      52 to -45. An EMSA using an anti-Sp1 antibody indicated that Sp1 specifically
      bound to the -52 to +64 region.

PMID- 15863388
TI  - Exogenous interleukin-6 increases cold allodynia in rats with a mononeuropathy.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine, signaling intracellularly via its
      unique membrane-bound receptor IL-6R and gp130. In peripheral nerve injury
      models, IL-6 and IL-6R are increased at the injured nerve and the respective
      dorsal root ganglion. IL-6 is increased at the ipsilateral dorsal and ventral
      horn of the spinal cord. IL-6 is known to affect neuronal survival,
      differentiation and regeneration. It is involved in synaptic plasticity and
      hyperexitability and induces the synthesis or release of other substances with
      known neuroprotective or neuromodulatory effects. In this study, intrathecal
      administration of recombinant rat IL-6 to rats with a chronic constriction injury
      of the sciatic nerve, induced a logarithmic dose-dependent increase in cold
      allodynia with a threshold of 10 pg IL-6 and a maximal effect at 100 ng IL-6.
      Intrathecal administration of saline or denaturated IL-6 was without effect. In
      rats with a chronic constriction injury, systemic administered IL-6 did not
      induce a hyperalgesic effect, illustrating that IL-6 acts at the level of the
      dorsal root ganglion or the spinal cord. Intraplantar injection of 100 ng IL-6 in
      the operated hind paw resulted in an increased cold allodynia. This study
      demonstrates that the sensitivity to exogenous intrathecal or peripheral IL-6
      increases in rats with a mononeuropathy.

PMID- 15863389
TI  - Measurement of gp130 cytokines oncostatin M and IL-6 in gingival crevicular fluid
      of patients with chronic periodontitis.
AB  - Several proinflammatory cytokines can induce periodontal tissue destruction and
      are thought to be useful indicators or diagnostic markers for periodontitis.
      Here, we aimed to investigate whether oncostatin M (OSM) was present in gingival
      crevicular fluid (GCF) and to clarify the correlation of GCF OSM and interleukin
      6 (IL-6) levels with the severity of periodontitis. Sixty-two sites in 14
      patients were divided into 4 groups based on probing depth (PD) and bleeding on
      probing (BOP). GCF was collected using paper strips from clinically health sites
      (PD < or = 3 mm, CAL: 1-3 mm, without BOP, n = 31), mildly diseased sites (PD <
      or = 3 mm, CAL: 3-5 mm, with BOP, n = 11), moderately diseased sites (PD = 4-6
      mm, CAL: 5-8 mm, with BOP, n = 11), and severely diseased sites (PD > 6 mm, CAL:
      8-12 mm, with BOP, n = 9). IL-6 and OSM in GCF were quantified by enzyme-linked
      immunosorbent assay and are expressed as concentrations (pg/ml) and total amounts
      (pg/site). Correlations of OSM and IL-6 levels with the severity of periodontitis
      in all groups were determined using Spearman rank correlation (r(s)). Our results
      showed that OSM and IL-6 were detected in most GCF samples. The total amounts of
      OSM and IL-6 were significantly positive correlated with severity of diseased
      sites (OSM: r(s) = 0.526, p < 0.01; IL-6: r(s) = 0.729, p < 0.01). No
      correlations of OSM or IL-6 concentration in GCF were found with disease
      severity. OSM and IL-6 levels in GCF were positively correlated to each other
      when expressed as either concentrations or total amounts (concentrations: r =
      0.485, p < 0.01; total amounts r = 0.490, p < 0.01). In conclusion, our findings
      suggest that IL-6 and OSM may play a role in modulating the inflammatory cascade
      of chronic periodontitis.

PMID- 15863390
TI  - Mouse genetic background influences severity of immune responses following trauma
      hemorrhage.
AB  - Studies have shown that following bacterial infection or endotoxin
      administration, immune functions are regulated differently in mice of different
      genetic background. Since the susceptibility to sepsis following trauma
      hemorrhage is dependant on the severity of injury, it is important to determine
      whether genetic background of the animal influence immune functions after trauma
      hemorrhage. The aim of our studies, therefore, was to assess differences in the
      immune functions in genetically different strains of age-matched C3H/HeN and
      C57BL/6 male mice following trauma-hemorrhage. The analysis for immune functions
      included: proliferation of splenocyte and bone-marrow cells, IL-2 and IFN-gamma
      release by splenocytes, and TNF-alpha and IL-10 release by splenic, peritoneal,
      liver (Kupffer cell), and bone-marrow macrophages. The results show significant
      differences in splenocyte and bone-marrow functions, and in the release of the
      mediators of immune function by immune competent cells: (a) between the two
      genetic strains, and (b) in each mouse strain following trauma-hemorrhage. Thus,
      genetic background appears to significantly influence the severity of immune
      responses in males following trauma-hemorrhage.

PMID- 15863391
TI  - Caffeine inhibits cytokine expression in lymphocytes.
AB  - Caffeine alters intracellular calcium signalling patterns in lymphocytes which
      are important for the specific regulation of activation and effector function in
      lymphocytes. The effect of caffeine on calcium signalling is probably mediated
      via a ryanodine receptor type 3 dependent intracellular calcium store which
      releases calcium after exposure to caffeine. Also, caffeine decreases lymphocyte
      cytotoxicity against allogenic myocyte. Which cytotoxic mechanisms are actually
      altered by caffeine is unknown. In mouse splenocyte cultures containing about 87%
      lymphocytes we show that concanavalin A (ConA, 5 microg/ml) stimulated cells
      increase the expression of TNF-alpha, IL-2 and IFN-gamma (ELISA) significantly.
      Caffeine (3.75 mM) inhibits cytokine expression of ConA stimulated cells almost
      completely. Ryanodine (1 microM) specifically blocks ryanodine receptors and
      thereby prevents caffeine induced calcium release. In our experiments, however,
      ryanodine has no effect on ConA stimulated IL-2 and IFN-gamma expression and only
      suppresses TNF-alpha expression by 20%. Furthermore, ryanodine does not prevent
      the inhibitory effect of caffeine on TNF-alpha, IL-2 and IFN-gamma expression in
      stimulated effector cells. We postulate that caffeine suppresses cytokine
      expression and thereby contributes to decreased cytotoxicity of lymphocytes
      against allogenic myocytes. The ryanodine receptor dependent intracellular
      calcium store does not seem to play a significant role in this process. Possibly,
      the blockade of IP3 receptors by caffeine is more important for cytokine
      suppression.

PMID- 15863392
TI  - A functional polymorphism of the tumor necrosis factor receptor-II gene
      associated with the survival and relapse prediction of breast carcinoma.
AB  - OBJECTIVE: Recently, we showed the implication of the polymorphism in tumor
      necrosis factor-alpha (TNF-alpha) gene in the susceptibility and prognosis of
      breast carcinoma. TNF-alpha acts through its receptors: types I and II. The
      TNFRII, expressed on the haematopoietic cells, is the high affinity receptor
      involved in mediating the biological effects of TNF-alpha. We investigated the
      susceptibility and prognostic implications of the genetic variation in the TNFRII
      in breast carcinoma. METHODS: We used the polymerase chain reaction and
      restriction enzyme digestion to characterize the variation of the TNFRII gene in
      300 unrelated Tunisian patients with breast carcinoma and 200 healthy control
      subjects. Associations of the genetic marker with the rates of the breast
      carcinoma-specific overall survival and the disease-free survival were assessed.
      RESULTS: A significant association was found between TNFRII-196M/R heterozygous
      genotype and breast carcinoma (OR = 1.61; P = 0.02). This association was more
      significant in post-menopausal patients (OR = 2.41, P = 0.0001). The 196R-TNFRII
      allele showed a significant association with increased overall survival and
      disease-free survival in breast carcinoma patients. CONCLUSION: Genetic variation
      in TNFRII may predict the late onset of breast carcinoma, relapse and death for
      patients with breast carcinoma.

PMID- 15863393
TI  - IL-12 and IL-10 polymorphisms and their effects on cytokine production.
AB  - Interleukin (IL)-12 is an inducer of differentiation of T helper (Th) cells
      towards Th1, whereas IL-10 is mainly an anti-inflammatory cytokine inhibiting Th1
      functions. Single nucleotide polymorphisms (SNPs) in the regulatory sequences of
      genes are presumed to be associated with the differential production of
      cytokines. One IL12B 3'untranslated region (UTR) and five of IL10 gene promoter
      region SNPs were screened in 152 individuals by genotyping. IL-10 and IL-12
      secretion of lipopolysaccharide (LPS), purified protein derivative (PPD) and
      Staphylococcus aureus Cowan strain I (SAC) stimulated peripheral blood
      mononuclear cells (PBMCs) was determined. The frequencies of the less frequent
      IL12B +16974 C, IL10 -2763 A -3575 A, -1082 G, -819 T and -592 A alleles were
      27.4, 32.2, 25.9, 14.8, 9.3 and 8.6%, respectively. Individuals CC homozygous at
      IL12B 3'UTR had significantly higher IL-12 secretion levels from LPS and PPD
      stimulated PBMCs than AC heterozygotes (P = 0.03 and P = 0.02) or AA homozygotes
      (P = 0.02 and P = 0.05, respectively). IL10 -2763 and -3575 SNPs did not show any
      effect on in vitro secretion levels, whereas the association of proximal promoter
      -1082 SNP with IL-10 production is confirmed. IL10 proximal and distal promoter
      SNP distribution with estimated haplotype variations has implicated considerable
      similarities with the Caucasian populations in Turkey.

PMID- 15863394
TI  - Neutralisation of TGF beta or binding of VLA-4 to fibronectin prevents rat tendon
      adhesion following transection.
AB  - Following tendon injury, severe loss of function often occurs either as a result
      of obliteration of the synovial canal with fibrous scar tissue or from rupture of
      the repaired tendon. The role of cell engineering in tendon repair is to promote
      strong and rapid healing of tendon whilst at the same time facilitating rapid
      reconstitution of the synovial canal. Modification of the immediate inflammatory
      response around healing tendon has been found to be of value. Experimentally this
      has been achieved by neutralisation of transforming growth factor-beta over the
      first 3 days following injury, or by blockade of inflammatory cell binding to the
      CS-1 locus on fibronectin with an anti-VLA-4 antibody, or with the synthetic VLA
      4 inhibitor, CS-1 peptide, in a rat model of tendon transection. It is concluded
      from this pilot study that the treatments described hold promise in improving
      outcomes of the common clinical problem of tendon injury in man.

PMID- 15863395
TI  - Circulating interleukin-18 and osteopontin are useful to evaluate disease
      activity in patients with tuberculosis.
AB  - BACKGROUND: T helper type 1 (Th1) responses have been implicated in the
      protective immunity, pathophysiology and development of tuberculosis. However, it
      is still unclear which molecule(s) reflect disease activity in patients with
      tuberculosis. METHODS: By specific enzyme immunoassays, circulating interferon
      gamma. (IFN-gamma), interleukin-12 (IL-12), IL-18 and osteopontin (OPN) were
      measured in 47 patients with pulmonary tuberculosis and 7 patients with miliary
      tuberculosis before anti-tuberculosis therapy, and also measured in 19 patients
      with tuberculosis before and after anti-tuberculosis therapy. RESULTS:
      Circulating IFN-gamma, IL-18 and OPN levels were significantly higher in patients
      with pulmonary tuberculosis than in healthy controls, while there was no
      significant difference in levels of circulating IL-12 between tuberculosis
      patients and controls. Circulating IFN-gamma, IL-12, IL-18 and OPN paralleled the
      extent of lung lesions, and circulating IFN-gamma, IL-18 and OPN paralleled the
      magnitude of fever in patients with pulmonary tuberculosis. Patients with miliary
      tuberculosis had extremely high levels of circulating OPN, IFN-gamma and IL-18.
      Circulating IL-18 and OPN were significantly decreased with anti-tuberculosis
      therapy, whereas circulating IL-12 and IFN-gamma were not. CONCLUSIONS: Among Th1
      response associated molecules, circulating levels of IL-18 and OPN, but not IFN
      gamma or IL-12, reflect disease activity in patients with tuberculosis.

PMID- 15863396
TI  - S-adenosyl methionine decarboxylase activity is required for the outcome of
      herpes simplex virus type 1 infection and represents a new potential therapeutic
      target.
AB  - All the available antiherpetic drugs are directed against viral proteins. Their
      extensive clinical use has led to the emergence of resistant viral strains. There
      is a need for the treatment of herpes infections due to resistant strains,
      especially for immunocompromised patients. To design new kinds of drugs, we have
      developed a strategy to identify cellular targets. Herpes simplex virus type 1
      (HSV-1) infection is concomitant to a repression of most host protein synthesis.
      However, some cellular proteins continue to be efficiently synthesized. We
      speculated that some of them could determine the outcome of infection. Since two
      polyamines, spermidine and spermine, are components of the HSV-1 virions, we
      investigated whether enzymes involved in their synthesis could be required for
      viral infection. We show that inhibition of S-adenosyl methionine decarboxylase,
      a key enzyme of the polyamine metabolic pathway, prevents HSV-1 infection.
      Inhibition of polyamine synthesis prevents infection of culture cells with HSV-1
      laboratory strains as well as clinical isolates that are resistant to the
      conventional antiviral drugs acyclovir and foscarnet. Our data provide the
      opportunity to develop molecules with a novel mechanism of action for the
      treatment of herpes infection.

PMID- 15863397
TI  - Merits of a New Drug Trial for ALS?

PMID- 15863398
TI  - Performance of a population-based cardiac risk stratification tool in Asian
      patients with chest pain.
AB  - OBJECTIVES: Most contemporary cardiac risk stratification tools have been derived
      and validated in mixed-race populations. Their validity in single-race
      populations has not been tested. The authors sought to compare the performance of
      a risk stratification tool between a mixed-race U.S. patient population and an
      Asian patient population. METHODS: This study is an analysis of data from the
      Internet Tracking Registry for Acute Coronary Syndromes (i(*)trACS) registry of
      patients with chest pain presenting to the emergency departments of eight U.S.
      centers and one site in Singapore. The Acute Cardiac Ischemia Time-Insensitive
      Predictive Instrument (ACI-TIPI) was computed for included patients, and its
      performance in predicting acute coronary syndrome (ACS) was compared between
      patients from the United States and Singapore. RESULTS: Of the 11,991 included
      patients, 1,120 experienced ACS. Although the ACI-TIPI demonstrated similar
      accuracy among groups (area under the curve, 0.729 [U.S.] vs. 0.719 [Singapore];
      p = 0.5611), sensitivity and specificity were different when equal ACI-TIPI
      thresholds were considered. Recreating the logistic regression models used to
      create the ACI-TIPI showed similar results between the derived parameters and the
      parameters estimated for the U.S. group. In contrast, age older than 50 years
      (log-odds ratio [LOR], 0.107; 95% confidence interval [CI] = 0.518 to 0.713),
      male gender (LOR, 0.487; 95% CI = 0.149 to 1.122), and chest pain as a primary
      complaint (LOR, 0.237; 95% CI = 0.139 to 0.613) had little predictive power in
      patients from Singapore. CONCLUSIONS: Differences exist in presentation and
      factors associated with ACS among patients from the United States and Singapore
      that may affect the performance of risk stratification tools. These findings
      suggest that cardiac clinical decision rules need international validation.

PMID- 15863399
TI  - Early glycoprotein IIb/IIIa inhibitor use for non-ST-segment elevation acute
      coronary syndrome: patient selection and associated treatment patterns.
AB  - OBJECTIVES: The authors analyzed contemporary use of glycoprotein (GP) IIb/IIIa
      inhibitors in patients with non-ST-segment elevation acute coronary syndrome
      (NSTE ACS) to determine patient selection patterns with early (<24 hours) GP
      IIb/IIIa inhibitor use and the relationship between GP IIb/IIIa inhibitor therapy
      and use of other guidelines-recommended therapies for NSTE ACS. METHODS: Using
      the CRUSADE Quality Improvement Initiative database, patient characteristics, in
      hospital treatments, and outcomes for 65,424 patients with ischemic chest pain of
      <24 hours' duration and either positive cardiac markers or ischemic
      electrocardiographic changes were analyzed. Data were collected from 443 U.S.
      hospitals from January 2001 to June 2003. RESULTS: Only 35% of eligible patients
      received GP IIb/IIIa inhibitors <24 hours after hospital admission. Approximately
      one third of patients received GP IIb/IIIa inhibitors in the emergency
      department, one third in the coronary care unit, and one third in the
      catheterization laboratory. Admission to a cardiologist's care was the most
      significant associated factor with early GP IIb/IIIa inhibitor use, along with
      elevated cardiac markers or ST-segment deviation. Patients at high risk for
      adverse cardiac events due to advanced age, congestive heart failure, or female
      gender were less likely to receive early GP IIb/IIIa inhibitor therapy. Patients
      who received early GP IIb/IIIa inhibitor therapy were more likely to receive
      other guidelines-recommended therapies. CONCLUSIONS: Despite the American College
      of Cardiology/American Heart Association (ACC/AHA) guidelines recommendations,
      early GP IIb/IIIa inhibitor therapy remains underutilized in patients with NSTE
      ACS and administration of early GP IIb/IIIa inhibitors is directed toward lower
      risk patients. Early GP IIb/IIIa inhibitor therapy is associated with improved
      overall adherence to the ACC/AHA guidelines.

PMID- 15863400
TI  - Precise and parallel characterization of coding polymorphisms, alternative
      splicing, and modifications in human proteins by mass spectrometry.
AB  - The human proteome is a highly complex extension of the genome wherein a single
      gene often produces distinct protein forms due to alternative splicing, RNA
      editing, polymorphisms, and posttranslational modifications. Such biological
      variation compounded by the high sequence identity within gene families currently
      overwhelms the complete and routine characterization of mammalian proteins by MS.
      A new data base of human proteins (and their possible variants) was created and
      searched using tandem mass spectrometric data from intact proteins. This first
      application of top down MS/MS to wild-type human proteins demonstrates both gene
      specific identification and the unambiguous characterization of multifaceted mass
      shifts (Deltam values). Such Deltam values found from the precise identification
      of 45 protein forms from HeLa cells reveal 34 coding single nucleotide
      polymorphisms, two protein forms from alternative splicing, and 12 diverse
      modifications (not including simple N-terminal processing), including a
      previously unknown phosphorylation at 10% occupancy. Automated protein
      identification was achieved with a median expectation value of 10(-13) and often
      occurred simultaneously with dissection of diverse sources of protein variability
      as they occur in combination. Top down MS therefore has a bright future for
      enabling precise annotation of gene products expressed from the human genome by
      non-mass spectrometrists.

PMID- 15863401
TI  - Induction of apoptosis in mouse liver by microcystin-LR: a combined
      transcriptomic, proteomic, and simulation strategy.
AB  - Microcystins (MCs) are a family of cyclic heptapeptide hepatotoxins produced by
      freshwater species of cyanobacteria that have been implicated in the development
      of liver cancer, necrosis, and even deadly intrahepatic bleeding. MC-LR, the most
      toxic MC variant, is also the most commonly encountered in a contaminated aquatic
      system. This study presents the first data in the toxicological research of MCs
      that combines the use of standard apoptotic assays with transcriptomics,
      proteomic technologies, and computer simulations. By using histochemistry, DNA
      fragmentation assays, and flow cytometry analysis, we determined that MC-LR
      causes rapid, dose-dependent apoptosis in mouse liver when BALB/c mice are
      treated with MC-LR for 24 h at doses of either 50, 60, or 70 microg/kg of body
      weight. We then used gene expression profiling to demonstrate differential
      expressions (>2-fold) of 61 apoptosis-related genes in cells treated with MC-LR.
      Further proteomic analysis identified a total of 383 proteins of which 35
      proteins were up-regulated and 30 proteins were down-regulated more than 2.5-fold
      when compared with controls. Combining computer simulations with the
      transcriptomic and proteomic data, we found that low doses (50 microg/kg) of MC
      LR lead to apoptosis primarily through the BID-BAX-BCL-2 pathway, whereas high
      doses of MC-LR (70 microg/kg) caused apoptosis via a reactive oxygen species
      pathway. These results indicated that MC-LR exposure can cause apoptosis in mouse
      liver and revealed two independent pathways playing a major regulatory role in MC
      LR-induced apoptosis, thereby contributing to a better understanding of the
      hepatotoxicity and the tumor-promoting mechanisms of MCs.

PMID- 15863402
TI  - Effectiveness of preventive care programmes in the elderly.

PMID- 15863403
TI  - Liaison psychiatry for older people--an overlooked opportunity.

PMID- 15863404
TI  - Depression as a risk factor for later dementia: a robust relationship?

PMID- 15863405
TI  - Counting the true cost of antiplatelet therapy for stroke prevention.

PMID- 15863406
TI  - Hypodermoclysis--a victim of historical prejudice.
AB  - Hypodermoclysis (HDC) had fallen into disrepute after adverse clinical incidents
      that were obviously the result of improper use of an ingenious technique. HDC has
      clear advantages over alternative parenteral routes. It has stood the rigour of
      scientific scrutiny but failed to regain its past glory. This is possibly because
      of our ignorance and inability to detach ourselves from an age-old prejudice.
      This is an attempt to demystify some of the myths that surround it. The hope is
      that older people are not denied an element of health care that they are perhaps
      most well suited to.

PMID- 15863407
TI  - Prediction of appropriate timing of palliative care for older adults with non
      malignant life-threatening disease: a systematic review.
AB  - BACKGROUND: most people in contemporary western society die of the chronic
      diseases of old age. Whilst palliative care is appropriate for elderly patients
      with chronic, non-malignant disease, few of these patients access such care
      compared with cancer patients. Objective referral criteria based on accurate
      estimation of survival may facilitate more timely referral of non-cancer patients
      most appropriate for specialist palliative care. OBJECTIVE: to identify tools and
      predictor variables that might aid clinicians estimate survival and assess
      palliative status in non-cancer patients aged 65 years and older. METHODS:
      systematic review and quality assessment using criteria modified from the
      literature. RESULTS: 11 studies that evaluated prognoses in hospitalised and
      community-based older adults with non-malignant disease were identified. Key
      generic predictors of survival were increased dependency of activities of daily
      living, presence of comorbidities, poor nutritional status and weight loss, and
      abnormal vital signs and laboratory values. Disease-specific predictors of
      survival were identified for dementia, chronic obstructive pulmonary disorder and
      congestive heart failure. No study evaluated the relationship between survival
      and palliative status. CONCLUSION: prognostic models that attempt to estimate
      survival of < or = 6 months in non-cancer patients have generally poor
      discrimination, reflecting the unpredictable nature of most non-malignant
      disease. However, a number of generic and disease-specific predictor variables
      were identified that may help clinicians identify older, non-cancer patients with
      poor prognoses and palliative care needs. Simple, well-validated prognostic
      models that provide clinicians with objective measures of palliative status in
      non-cancer patients are needed. Additionally, research that evaluates the effect
      of general and specialist palliative care on psychosocial outcomes in non-cancer
      patients and their carers is needed.

PMID- 15863408
TI  - Reliability of the Barthel Index when used with older people.
AB  - OBJECTIVE: the Barthel Index (BI) has been recommended for the functional
      assessment of older people but the reliability of the measure for this patient
      group is uncertain. To investigate this issue we undertook a systematic review to
      identify relevant studies from which an overview is presented. METHOD: studies
      investigating the reliability of the BI were obtained by searching Medline,
      Cinahl and Embase to January 2003. Screening for potentially relevant papers and
      data extraction of the studies meeting the inclusion criteria were carried out
      independently by two researchers. RESULTS: the scope of the 12 studies identified
      included all the common clinical settings relevant to older people. No study
      investigated test-retest reliability. Inter-rater reliability was reported as
      'fair' to 'moderate' agreement for individual BI items, and a high percentage
      agreement for the total BI score. However, these findings were difficult to
      interpret as few studies reported the prevalence of the disability categories for
      the study populations. There may be considerable inter-observer disagreement (95%
      CI of +/-4 points). There was evidence that the BI might be less reliable in
      patients with cognitive impairment and when scores obtained by patient interview
      are compared with patient testing. The role of assessor training and/or
      guidelines on the reliability of the BI has not been investigated. CONCLUSIONS:
      although the BI is highly recommended, there remain important uncertainties
      concerning its reliability when used with older people. Further studies are
      justified to investigate this issue.

PMID- 15863409
TI  - Prevalence of cognitive impairment: results from the MRC trial of assessment and
      management of older people in the community.
AB  - BACKGROUND: cognitive impairment is an important part of the diagnostic criteria
      for dementia. The Mini-Mental State Examination (MMSE) is recommended to test for
      cognitive impairment and to monitor medication response. OBJECTIVES: we examined
      the prevalence of cognitive impairment in the UK and assessed associations with
      cognitive impairment. DESIGN: cross-sectional survey as part of a cluster
      randomised trial. SUBJECTS: representative sample of people aged 75 years and
      over. METHODS: all subjects had a detailed baseline health assessment including
      the MMSE. RESULTS: a total of 15,051 subjects completed the assessment (71.9%).
      Almost two-thirds of subjects were female (61.5%) and almost half were aged
      between 75 and 79 years (47.0%). The prevalence of cognitive impairment was 18.3%
      (95% confidence intervals (CI) = 16.0-20.9) at a cut-off of 23/24, and 3.3% (95%
      CI = 2.8-4.0) at 17/18. Those with impairment (MMSE 23/24) were significantly
      more likely to have hearing (odds ratio (OR) 1.7), vision (OR 1.7) and urinary
      incontinence problems (OR 1.3), have two or more falls in the previous 6 months
      (OR 1.4), and report poorer health (OR 1.9). Almost half the participants lived
      alone (n = 7,073; 47.0%) and of these almost one-fifth were impaired (MMSE 23/24;
      19.4%). CONCLUSIONS: there was a high prevalence of cognitive impairment. This
      representative sample demonstrates the potential burden of disease and service
      demands. It supports the need for a broader assessment of functioning as
      recommended by the National Service Framework for Older People, particularly in
      people with cognitive impairment.

PMID- 15863410
TI  - Does ingestion of cranberry juice reduce symptomatic urinary tract infections in
      older people in hospital? A double-blind, placebo-controlled trial.
AB  - BACKGROUND: cranberry juice is often given to older people in hospital to prevent
      urinary tract infection (UTI), although there is little evidence to support its
      use. OBJECTIVE: to assess whether cranberry juice ingestion is effective in
      reducing UTIs in older people in hospital. DESIGN: randomised, placebo
      controlled, double-blind trial. SETTING: Medicine for the Elderly assessment and
      rehabilitation hospital wards. SUBJECTS: 376 older patients in hospital. METHODS:
      participants were randomised to daily ingestion of 300 ml of cranberry juice or
      matching placebo beverage. The primary outcome was time to onset of first UTI.
      Secondary outcomes were adherence to beverage drinking, courses of antibiotics
      prescribed, and organisms responsible for UTIs. RESULTS: a total of 21/376 (5.6%)
      participants developed a symptomatic UTI: 14/189 in the placebo group and 7/187
      in the cranberry juice group. These between-group differences were not
      significant, relative risk (RR) 0.51 [95% CI 0.21-1.22, P = 0.122). Although
      there were significantly fewer infections with Escherichia coli in the cranberry
      group (13 versus 4) RR 0.31 [95% CI 0.10-0.94, P = 0.027], this should be
      interpreted with caution as it was a secondary outcome. CONCLUSION: despite
      having the largest sample size of any clinical trial yet to have examined the
      effect of cranberry juice ingestion, the actual infection rate observed was lower
      than anticipated, making the study underpowered. This study has confirmed the
      acceptability of cranberry juice to older people. Larger trials are now required
      to determine whether it is effective in reducing UTIs in older hospital patients.

PMID- 15863411
TI  - Cognitive assessment of a representative community population with Parkinson's
      disease (PD) using the Cambridge Cognitive Assessment-Revised (CAMCOG-R).
AB  - BACKGROUND: cognitive decline is well recognised in Parkinson's disease (PD) but
      the best cognitive assessment tool for use in such patients remains unclear. The
      30-point Mini-Mental State Examination (MMSE), while quick and straightforward to
      use, fails to cover a full range of cognitive domains and is recognised to have a
      ceiling effect. The Cambridge Cognitive Assessment-Revised (CAMCOG-R) is a
      cognitive screening tool allowing the assessment of a number of different domains
      of cognition. It has not previously been used specifically on PD subjects.
      METHODS: a prevalent community population of 135 PD patients were assessed
      cognitively using the MMSE. Those scoring 25 or above on the MMSE were
      subsequently further assessed using CAMCOG-R. Demographic and disease factors
      including disease duration, symptom severity, anxiety, depression and the
      presence of hallucinations were recorded for each participant. RESULTS: 31/135
      (23%) demonstrated cognitive impairment on the MMSE (score < 25). Ninety-four of
      the remaining group (10 were excluded) achieved a median total CAMCOG-R score of
      89/104. The results were widely distributed. The subjects scored particularly
      highly in the cognitive domains of orientation, comprehension and perception but
      relatively poorly at memory and abstract thinking. Significantly poorer scores (P
      < 0.05) were seen throughout the cognitive domains with increasing age,
      increasing PD symptom severity and increasing disease duration, but not with the
      presence of anxiety, depression or hallucinations in the subjects. DISCUSSION:
      CAMCOG-R was found to be a viable and useful cognitive screening tool for use in
      PD. A wide range of cognitive ability was demonstrated in subjects who had been
      assessed previously by the MMSE as not having significant cognitive impairment.
      The group performed worse in certain cognitive domains than others and those who
      were older, with more severe PD symptoms and with symptoms for longer, scored
      less well.

PMID- 15863412
TI  - Fear of falling limiting activity in young-old women is associated with reduced
      functional mobility rather than psychological factors.
AB  - BACKGROUND: many older people experience fear of falling. This is sometimes
      associated with activity limitation, with potential adverse health implications.
      The explanatory contributions of physical and psychosocial factors to this
      syndrome are unclear. OBJECTIVES: to examine the associations between fear of
      falling limiting activity (FoF-LA) among young-old women with (i) functional
      capacity and (ii) psychological factors. SUBJECTS AND METHODS: FoF-LA, functional
      difficulty and dependency, psychological factors, previous falls, visual and
      hearing handicap, memory, pain, and habitual physical activity were assessed
      using standard questionnaires in 713 community-dwelling London women, mean age
      64.2 years. RESULTS: 70 women (10.1%) reported FoF-LA, of whom 21 had fallen in
      the previous year. Women reporting FoF-LA had higher prevalence of adverse
      functional and clinical characteristics. Multiple logistic regression analyses
      showed that both mild ('changes in the way walk half a mile') and moderate
      ('difficulty standing from armless chair') reduction in functional capacity were
      independently associated with FoF-LA (odds ratios 4.02 (95% CI 1.5-10.7) and 5.07
      (CI 2.0-13.0) respectively) after adjustment for age, falls and clinical factors.
      Psychological factors and perceived fair/poor health were bivariately but not
      independently associated with FoF-LA; after adjustment for them, mild and
      moderate reductions in functional capacity remained strongly associated with FoF
      LA (OR 4.02 (CI 1.5-10.7) and 3.83 (CI 1.4-10.5) respectively), along with visual
      handicap and increased health service use. CONCLUSIONS: among young-old women,
      FoF-LA is related to early reduction of mobility function rather than
      psychological factors. It may identify individuals at risk of subsequent
      functional decline.

PMID- 15863413
TI  - The Caregivers for Alzheimer's disease Problems Scale (CAPS): development of a
      new scale within the LASER-AD study.
AB  - BACKGROUND: we developed the Caregivers for Alzheimer's disease Problems Scale
      (CAPS) comprising common risk factors for anxiety and depression for family
      carers of people with dementia. OBJECTIVE: to calculate the sensitivity and
      specificity of the CAPS in order to measure its usefulness in identifying
      dementia caregivers at risk of anxiety and depression and therefore whether it
      identifies clinically relevant areas for intervention or highlights the need for
      support if the problem could not be changed. METHOD: 153 family caregivers were
      interviewed as part of a larger epidemiologically representative study of people
      with Alzheimer's disease and their caregivers. Caregiver anxiety and depression
      were measured using the Hospital Anxiety and Depression Scale (HADS). RESULTS:
      the CAPS had high sensitivity and specificity in detecting caregivers with screen
      positive anxiety and depression. Five areas were indicated: neuropsychiatric
      symptoms and depression in the care-recipient, co-residence and relationships
      with the care-recipient, and physical health of the caregiver. CONCLUSIONS:
      awareness of these problems can help clinicians identify those carers most likely
      to be anxious or depressed and indicate appropriate intervention and support. We
      recommend that this instrument be used as part of routine assessments of people
      with dementia and their families.

PMID- 15863414
TI  - Hospitalisations before and after nursing home admission: a retrospective cohort
      study from Germany.

PMID- 15863415
TI  - Having had a hip fracture--association with dependency among the oldest old.

PMID- 15863416
TI  - The use of the Tempa.Dot thermometer in routine clinical practice.

PMID- 15863417
TI  - A study of the management of COPD according to established guidelines and the
      implications for older patients.

PMID- 15863418
TI  - The effect of glucose-potassium-insulin (GKI) infusion on the blood pressure and
      hormonal response to acute stroke.

PMID- 15863419
TI  - An unusual case of weight loss in a patient with refractory rheumatoid arthritis.
AB  - We describe a case of metastatic malignant melanoma with no primary cutaneous
      lesion presenting as weight loss in a man with refractory, seropositive
      rheumatoid arthritis (RA). The patient had undergone multiple investigations
      previously and the case highlights the importance of repeat assessment in elderly
      patients presenting with unexplained weight loss.

PMID- 15863420
TI  - Orthostatic hypotension in an octogenarian--an unusual presentation.
AB  - Orthostatic hypotension is a common problem in older adults and can be associated
      with falls, dizziness and syncope and their associated consequences. Therefore,
      it is important to recognise the condition and institute appropriate management.
      We report an elderly woman who presented with orthostatic hypotension and was
      found to have a rare, benign yet potentially fatal condition.

PMID- 15863421
TI  - A 75-year-old woman with a lung nodule--a spontaneous pulmonary haematoma
      associated with bronchiectasis.

PMID- 15863423
TI  - Difficulties encountered in hospital falls prevention research.

PMID- 15863424
TI  - Does long-term warfarin affect the quality of life of older people?

PMID- 15863425
TI  - Post-stroke fatigue: an important yet neglected symptom.

PMID- 15863426
TI  - Three memorable patients.

PMID- 15863427
TI  - Adolescent cigarette smoking: a commentary and issues for pediatric psychology.

PMID- 15863428
TI  - Images of smokers and willingness to smoke among African American pre
      adolescents: an application of the prototype/willingness model of adolescent
      health risk behavior to smoking initiation.
AB  - OBJECTIVE: This study used the prototype/willingness model of adolescent health
      risk behavior to examine factors related to onset of smoking. METHODS: Two waves
      of data were collected from a panel of 742 African American children (mean
      age=10.5 at Wave 1) and their primary caregivers. Measures included cognitions
      outlined by the prototype model as well as self-reports of smoking by the parent
      and child. RESULTS: Structural equation modeling revealed a pattern consistent
      with expectations generated by the prototype model. The relation between
      contextual, familial, and dispositional factors-including neighborhood risk,
      parental smoking, and children's academic orientation-and the initiation of
      smoking at Wave 2, two years later, was mediated by the children's cognitions.
      Primary among these cognitions were the children's images of smokers and
      children's willingness to smoke. CONCLUSIONS: Smoking cognitions mediate the
      impact of important distal factors (such as context, family environment, and
      disposition) on the onset of smoking in children. Perhaps more important, it is
      possible to predict onset of smoking in African American children as young as age
      10 by assessing the cognitive factors suggested by the prototype model.

PMID- 15863429
TI  - On the measurement of nicotine dependence in adolescence: comparisons of the mFTQ
      and a DSM-IV-based scale.
AB  - OBJECTIVE: To compare nicotine-dependent smokers identified by the modified
      Fagerstrom Tolerance Questionnaire (mFTQ) and a scale based on the Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition (DSM-IV), in a multiethnic
      adolescent sample. METHODS: A school survey was conducted on 6th- to 10th-grade
      students (N=15,007) in a large urban public school system. RESULTS: The two
      scales formed two distinct factors. The concordance between the two
      classifications of nicotine dependence was low. The DSM identified a much larger
      number of nicotine-dependent smokers than the mFTQ, mostly because smokers met
      dependence criteria at much lower levels of cigarettes consumed, especially when
      they were depressed. Rates of dependence were higher among whites than minority
      group members, especially African Americans. Control for level of cigarette
      consumption attenuated or eliminated ethnic differences. CONCLUSIONS: This
      investigation provides some understanding of youths defined as dependent by each
      scale but cannot by itself indicate which scale better measures dependence.
      Differences in dependence rates among ethnic groups are accounted for mostly by
      quantity of cigarettes smoked.

PMID- 15863430
TI  - Parenting style and smoking-specific parenting practices as predictors of
      adolescent smoking onset.
AB  - OBJECTIVE: To test whether parenting style and smoking-specific parenting
      practices prospectively predicted adolescent smoking. METHODS: Three hundred
      eighty-two adolescents (age 10-17 years, initial nonsmokers, 98% non-Hispanic
      whites) and their parents were interviewed, with smoking also assessed 1-2 years
      later. RESULTS: Adolescents from disengaged families (low acceptance and low
      behavioral control) were most likely to initiate smoking. Adolescents' reports of
      parents' smoking-related discussion was related to lowered smoking risk for
      adolescents with nonsmoking parents, but unrelated to smoking onset for
      adolescents with smoking parents. Smoking-specific parenting practices did not
      account for the effects of general parenting styles. CONCLUSIONS: Both parenting
      style and smoking-specific parenting practices have unique effects on adolescent
      smoking, although effects were largely confined to adolescents' reports; and for
      smoking-specific parenting practices, effects were confined to families with
      nonsmoking parents. Interventions that focus only on smoking-specific parenting
      practices may be insufficient to deter adolescent smoking.

PMID- 15863432
TI  - A comparison of tobacco-related risk factors between adolescents with and without
      cancer.
AB  - OBJECTIVE: To compare adolescents with and without cancer on current smoking
      status, intentions to smoke, and tobacco-related risk factors. METHODS: Ninety
      adolescents undergoing treatment for cancer (median time since diagnosis was 2.4
      months) and a comparison sample of 279 adolescents without cancer, ages 12 to 18
      years, completed questionnaires that asked about their smoking habits, intentions
      to smoke, and tobacco-related psychosocial risk factors. RESULTS: Approximately
      2% of adolescents with cancer and 22% of adolescents without cancer reported
      current smoking. Compared to nonsmoking adolescents without cancer, nonsmoking
      adolescents with cancer were one third less likely to report intentions to smoke.
      No significant interactions were detected between group (having cancer or not)
      and each of the tobacco-specific and psychosocial variables tested in two
      separate multivariable models. Intentions to smoke were best predicted by
      variables most proximal to smoking. Adolescents who smoked in the past and who
      had lower tobacco knowledge and greater perceived instrumental value were more
      likely to report intentions to smoke. Adolescents who were less optimistic were
      also more likely to intend to smoke. CONCLUSIONS: Tobacco-related risk factors
      for intentions to smoke appeared to be similar among adolescents with and without
      cancer. Implications of these findings for tobacco control among adolescents with
      cancer are discussed.

PMID- 15863433
TI  - Physician tobacco advice to preteens in a smoking-prevention randomized trial:
      steering clear.
AB  - OBJECTIVE: To examine preadolescent and parental recall of tobacco prevention
      messages by health care providers. METHODS: As part of a smoking prevention
      trial, providers were cued to reinforce the study and advise intervention
      participants (N=4,026) not to use tobacco. All parents were surveyed at baseline;
      children were surveyed at 20 months; and a subsample (504 households) was
      surveyed at 6 and 12 months to assess discussion of tobacco use prevention and
      other health behavior topics by providers as well as susceptibility and
      experimentation with tobacco among children. RESULTS: During the 20-month follow
      up, less than 25% of children recalled a provider discussing tobacco use
      prevention. Recall of exposure to tobacco prevention messages at school (68%),
      from parents (53%), and from mass media (71%) was higher. CONCLUSIONS: Physician
      tobacco counseling is occurring at lower rates in pre-adolescents than it is in
      adults. A chart reminder to providers was insufficient to create a meaningful
      effect.

PMID- 15863431
TI  - Coping skills and parent support mediate the association between childhood
      attention-deficit/hyperactivity disorder and adolescent cigarette use.
AB  - OBJECTIVE: To examine mediators of the association between childhood attention
      deficit/hyperactivity disorder (ADHD) and adolescent cigarette use. METHOD:
      Participants were 142 adolescents diagnosed with ADHD in childhood and 100
      adolescents without ADHD. RESULTS: Among probands, cigarette smoking was more
      frequent, adaptive coping skills (behavioral and cognitive) were fewer, and
      parental support was lower. Coping and support partially mediated the ADHD
      association with smoking. Persistence of ADHD and adolescent conduct disorder
      were also important. CONCLUSIONS: Vulnerability to smoking among probands may be
      partly due to fewer problem-solving resources. Coping skill deficits and parent
      child communication may be important treatment targets for smoking prevention.

PMID- 15863434
TI  - Spermatozoal nuclear determinants of reproductive outcome: implications for ART.
AB  - A male factor is implicated in more than 50% of couples treated with IVF.
      However, neither the routine testing of male fertility potential nor its
      treatment address the specific mechanisms by which spermatozoal factors may
      impact upon reproductive outcome. An important function of spermatozoa is to
      deliver the paternal genome to the oocyte. Recently, a number of acquired
      spermatozoal nuclear factors that may have implications on reproductive outcome
      have been described. These include non-specific DNA strand breaks, numerical
      abnormalities in spermatozoal chromosome content, Y chromosome microdeletions and
      alterations in the epigenetic regulation of paternal genome. The exact mechanisms
      by which these factors affect reproduction are unknown and their implications for
      assisted reproduction technology outcome need to be further investigated. These
      recent findings point to the need for novel and more personalized approaches to
      test and treat male factor infertility.

PMID- 15863435
TI  - The Arabidopsis root hair mutants der2-der9 are affected at different stages of
      root hair development.
AB  - Root hairs are an excellent model system to study cell developmental processes as
      they are easily accessible, single-celled, long tubular extensions of root
      epidermal cells. In a genetic approach to identify loci important for root hair
      development, we have isolated eight der (deformed root hairs) mutants from an
      ethylmethanesulfonate (EMS)-mutagenized Arabidopsis population. The der lines
      represent five new loci involved in root hair development and show a variety of
      abnormalities in root hair morphology, indicating that different root hair
      developmental stages are affected. A double mutant analysis with the short root
      hair actin2 mutant der1-2 confirmed that the der mutants are disturbed at
      different time points of root hair formation. Auxin and ethylene are known to be
      important for trichoblast cell fate determination and root hair elongation. Here,
      we show that they are able to suppress the phenotype of two der mutants. As the
      auxin- and ethylene-responsive der mutants are affected at different stages of
      root hair formation, our results demonstrate that the function of auxin and
      ethylene is not limited to cell differentiation and root hair elongation but that
      the two hormones are effective throughout the whole root hair developmental
      process.

PMID- 15863436
TI  - Obesity in middle age and future risk of dementia: a 27 year longitudinal
      population based study.
AB  - OBJECTIVE: To evaluate any association between obesity in middle age, measured by
      body mass index and skinfold thickness, and risk of dementia later in life.
      DESIGN: Analysis of prospective data from a multiethnic population based cohort.
      SETTING: Kaiser Permanente Northern California Medical Group, a healthcare
      delivery organisation. PARTICIPANTS: 10,276 men and women who underwent detailed
      health evaluations from 1964 to 1973 when they were aged 40-45 and who were still
      members of the health plan in 1994. MAIN OUTCOME MEASURES: Diagnosis of dementia
      from January 1994 to April 2003. Time to diagnosis was analysed with Cox
      proportional hazard models adjusted for age, sex, race, education, smoking,
      alcohol use, marital status, diabetes, hypertension, hyperlipidaemia, stroke, and
      ischaemic heart disease. RESULTS: Dementia was diagnosed in 713 (6.9%)
      participants. Obese people (body mass index > or = 30) had a 74% increased risk
      of dementia (hazard ratio 1.74, 95% confidence interval 1.34 to 2.26), while
      overweight people (body mass index 25.0-29.9) had a 35% greater risk of dementia
      (1.35, 1.14 to 1.60) compared with those of normal weight (body mass index 18.6
      24.9). Compared with those in the lowest fifth, men and women in the highest
      fifth of the distribution of subscapular or tricep skinfold thickness had a 72%
      and 59% greater risk of dementia, respectively (1.72, 1.36 to 2.18, and 1.59,
      1.24 to 2.04). CONCLUSIONS: Obesity in middle age increases the risk of future
      dementia independently of comorbid conditions.

PMID- 15863437
TI  - Effect of neurolytic nerve block on systemic carrageenan-induced inflammatory
      response in mice.
AB  - BACKGROUND: Local tissue inflammation caused by injury or inflammatory processes
      may be reduced by section or local anaesthetic block of the nerve innervating the
      inflamed area. METHODS: Using a neurolytic nerve block, we assessed the systemic
      inflammatory response elicited by a local injection of carrageenan in mice. Sixty
      mice received a unilateral sciatic nerve block with 70% ethanol followed 5 days
      later by an injection of carrageenan on the ipsilateral or contralateral hind
      paw. Whole blood was sampled 15 h after carrageenan injection. RESULTS: Fifty-six
      animals had a complete nerve block. Tumour necrosis factor-alpha (TNF-alpha),
      interleukin 1beta (IL-1beta) and interleukin 10 (IL-10) concentrations were
      measured in the plasma of 20 mice (10 in the ispilateral group and 10 in the
      contralateral group). In the remaining 36 mice (18 in each group), blood was
      cultured for 24 h in the presence of lipopolysaccharide or Staphylococcus aureus
      extract. TNF-alpha and IL-1beta production in the supernatant were, on average,
      30% lower in the ispilateral group than in the contralateral group. CONCLUSION: A
      prolonged nerve block decreases the systemic consequences of the local
      inflammatory reaction elicited by carrageenan injection.

PMID- 15863438
TI  - Randomized comparison of three methods of induction of anaesthesia with
      sevoflurane.
AB  - BACKGROUND: Rebreathing will occur if a low gas flow and a Mapleson D circuit are
      used to induce anaesthesia with a volatile anaesthetic agent. This has the
      advantage that it allows ventilation to be sustained when consciousness is lost,
      and specific manoeuvres such as breath-holding or vital capacity breaths are not
      needed to facilitate induction of anaesthesia. However, if the fresh gas flow
      were too small, this would slow induction by limiting the rate of delivery of the
      anaesthetic agent. To assess the impact of fresh gas flow and rebreathing, we
      compared induction using sevoflurane 8% given by three different methods.
      METHODS: We randomly allocated 65 patients to receive induction of anaesthesia
      from either a Mapleson A breathing system with a fresh gas flow of 9 litre min(
      1) (group A9), a Mapleson D system with a fresh flow of 6 litre min(-1) (group
      D6) or a Mapleson D system with a fresh flow of 3 litre min(-1) (group D3). We
      measured times for induction, end-tidal sevoflurane and end-tidal carbon dioxide.
      RESULTS: The median (quartiles) induction times were 58 (45, 72), 50 (42, 65) and
      64 (52, 92) s in the groups A9, D6 and D3 respectively. Induction of anaesthesia
      took longer (P<0.01) and was more variable in group D3. In this group, end-tidal
      sevoflurane concentration at the time of induction of anaesthesia was lower
      (P<0.05). In group A9, end-tidal carbon dioxide was less (P<0.05). CONCLUSIONS:
      In adult patients allowed to breathe normally, prompt and consistent inhalation
      induction of anaesthesia with sevoflurane is obtained when fresh gas flow is
      limited to 6 litre min(-1) from a Mapleson D circuit, but smaller flows are
      impractical.

PMID- 15863439
TI  - Preservation of static and dynamic cerebral autoregulation after mild hypothermic
      cardiopulmonary bypass.
AB  - BACKGROUND: Dysfunction of cerebral autoregulation might contribute to
      neurological morbidity after cardiac surgery. In this study, our aim was to
      assess the preservation of cerebral autoregulation after cardiac surgery
      involving cardiopulmonary bypass (CPB). METHODS: Dynamic and static components of
      cerebral autoregulation were evaluated in 12 patients undergoing coronary artery
      bypass graft surgery, anaesthetized with midazolam, fentanyl, and propofol, and
      using mild hypothermic CPB (31-33 degrees C). Arterial pressure (ABP), central
      venous pressure (CVP), and blood flow velocity in the middle cerebral artery
      (CBFV) were recorded. The cerebral perfusion pressure (CPP) was calculated as a
      difference between mean ABP and CVP. Rapid decrease of CPP was caused by a sudden
      change of patients' position from Trendelenburg to reverse Trendelenburg.
      Cerebral vascular resistance (CVR) was calculated by dividing CPP by CBFV. Index
      of static cerebral autoregulation (CAstat) was calculated as the change of CVR
      related to change of CPP during the manoeuvre. Dynamic rate of autoregulation
      (RoRdyn) was determined as the change in CVR per second during the first 4 s
      immediately after a decrease in CPP, related to the change of CPP. Measurements
      were obtained after induction of anaesthesia, and 15, 30, and 45 min after
      termination of CPB. RESULTS: No significant changes were found in CAstat or
      RoRdyn after CPB. Significant changes in CVR could be explained by concomitant
      changes in body temperature and haematocrit. CONCLUSION: Autoregulation of
      cerebral blood flow remains preserved after mild hypothermic CPB.

PMID- 15863440
TI  - Anaesthesia for peculiar cells--a century of sickle cell disease.
AB  - Sickle cell disease is a congenital haemoglobinopathy with a high incidence of
      perioperative complications. Traditional anaesthetic management, based largely on
      extrapolation from biochemical models, has emphasized avoidance of red cell
      sickling to prevent exacerbations of the disease. This historical review outlines
      the evolution of the traditional approach to sickle cell pathology, assesses the
      validity of this model, describes the emergence of the concept of the disease as
      one defined by chronic inflammatory vascular damage, and outlines the practical
      implications of this new approach.

PMID- 15863441
TI  - Multiple ryanodine receptor subtypes and heterogeneous ryanodine receptor-gated
      Ca2+ stores in pulmonary arterial smooth muscle cells.
AB  - Ryanodine receptors (RyRs) of pulmonary arterial smooth muscle cells (PASMCs)
      play important roles in major physiological processes such as hypoxic pulmonary
      vasoconstriction and perinatal pulmonary vasodilatation. Recent studies show that
      three subtypes of RyRs are coexpressed and RyR-gated Ca2+ stores are distributed
      heterogeneously in systemic vascular myocytes. However, the molecular identity
      and subcellular distribution of RyRs have not been examined in PASMCs. In this
      study we detected mRNA and proteins of all three subtypes in rat intralobar
      PASMCs using RT-PCR and Western blot. Quantitative real-time RT-PCR showed that
      RyR2 mRNA was most abundant, approximately 15-20 times more than the other two
      subtypes. Confocal fluorescence microscopy revealed that RyRs labeled with BODIPY
      TR-X ryanodine were localized in the peripheral and perinuclear regions and were
      colocalized with sarcoplasmic reticulum labeled with Fluo-5N. Immunostaining
      showed that the subsarcolemmal regions exhibited clear signals of RyR1 and RyR2,
      whereas the perinuclear compartments contained mainly RyR1 and RyR3. Ca2+ sparks
      were recorded in both regions, and their activities were enhanced by a
      subthreshold concentration of caffeine or by endothelin-1, indicating functional
      RyR-gated Ca2+ stores. Moreover, 18% of the perinuclear sparks were prolonged
      [full duration/half-maximum (FDHM) = 193.3 +/- 22.6 ms] with noninactivating
      kinetics, in sharp contrast to the typical fast inactivating Ca2+ sparks (FDHM =
      44.6 +/- 3.2 ms) recorded in the same PASMCs. In conclusion, multiple RyR
      subtypes are expressed differentially in peripheral and perinuclear RyR-gated
      Ca2+ stores; the molecular complexity and spatial heterogeneity of RyRs may
      facilitate specific Ca2+ regulation of cellular functions in PASMCs.

PMID- 15863442
TI  - The aryl hydrocarbon receptor is a regulator of cigarette smoke induction of the
      cyclooxygenase and prostaglandin pathways in human lung fibroblasts.
AB  - Cigarette smoking can lead to chronic lung inflammation and lung cancer. Chronic
      inflammation, associated with expression of cyclooxygenase-2 (COX-2) and
      prostaglandins, predisposes to malignancy. We recently demonstrated that human
      lung fibroblasts are activated by cigarette smoke to express COX-2 and
      prostaglandin E(2) (PGE(2)). Little is known about the mechanism whereby smoke
      activates human lung fibroblasts to produce proinflammatory mediators. Herein, we
      report the central role of the aryl hydrocarbon receptor (AHR) in cigarette smoke
      extract (CSE)-induced COX-2, microsomal PGE(2) synthase (mPGES), and PGE(2)
      production in human lung fibroblasts. Western blot analysis revealed that primary
      strains of human lung fibroblasts express AHR and aryl hydrocarbon nuclear
      translocator protein, supporting the possibility that smoke activates lung
      fibroblasts through this pathway. Experiments were subsequently performed to
      determine whether the AHR was activated by CSE. Immunocytochemistry and EMSA
      analysis revealed that CSE induced nuclear translocation of the AHR in human lung
      fibroblasts. CSE decreased protein levels of the AHR, consistent with AHR ligand
      induced proteosome-mediated degradation. CSE also induced mPGES-1 and COX-2
      protein and increased PGE(2) production. Treatment of human fibroblasts with AHR
      antagonists in the presence of CSE inhibited AHR nuclear translocation as well as
      COX-2, mPGES-1, and PGE(2) production. These data indicate that the AHR pathway
      plays an important role in cigarette smoke-mediated COX-2 and PG production in
      human lung fibroblasts and may contribute to tobacco-associated inflammation and
      lung disease.

PMID- 15863443
TI  - Airway hyperresponsiveness induced by cationic proteins in vivo: site of action.
AB  - Major basic protein and other native cationic proteins increase airway
      hyperresponsiveness when administered to the luminal surface of the airways in
      vitro. To determine whether the same applies in vivo, we assessed airway
      responsiveness in rats challenged with both aerosolized and intravenously infused
      methacholine. We partitioned total lung resistance into its airway and tissue
      components using the alveolar capsule technique. Neither poly-l-lysine nor major
      basic protein altered baseline mechanics or its dependence on positive end
      expiratory pressures ranging from 1 to 13 cmH(2)O. When methacholine was
      administered to the lungs as an aerosol, both cationic proteins increased
      responsiveness as measured by airway resistance, tissue resistance, and tissue
      elastance. However, responsiveness of all three parameters was unchanged when the
      methacholine was infused. Together, these findings suggest that cationic proteins
      alter airway responsiveness in vivo by an effect that is apparently limited to
      the bronchial epithelium.

PMID- 15863444
TI  - Autoregulation of CCL26 synthesis and secretion in A549 cells: a possible
      mechanism by which alveolar epithelial cells modulate airway inflammation.
AB  - Eotaxins (CCL11, CCL24, CCL26) originating from airway epithelial cells and
      leukocytes have been detected in bronchoalveolar lavage of asthmatics. Although
      the alveolar epithelium is the destination of uncleared allergens and other
      inflammatory products, scanty information exists on their contribution to the
      generation and regulation of the eotaxins. We envisioned a state whereby alveolar
      type II cells, a known source of other inflammatory proteins, could be involved
      in both the production and regulation of CCL24 and CCL26. Herein, we demonstrated
      that all three eotaxins are constitutively expressed in A549 cells. IL-4 and IL
      13 stimulated a concentration-dependent secretion of CCL24 and CCL26. The
      cytokines did not act synergistically. Cycloheximide and actinomycin D abrogated
      IL-4- and IL-13-dependent CCL26 but not CCL24 secretion. Both IL-13 and IL-4
      stimulated CCL26 synthesis that was inhibited in a concentration-dependent manner
      by CCL26 but not CCL24. Only CCL26 reduced expression of CCR3 receptors by 30
      40%. On the other hand, anti-CCR3 pretreatment reduced IL-4+IL-13-dependent CCL26
      secretion, implying autoregulation. A CCR3-specific antagonist (SB-328437)
      significantly decreased IL-4-dependent synthesis and release of CCL26.
      Eosinophils treated with medium from IL-4-stimulated A549 cells preincubated with
      anti-CCL26 showed a marked decrease of superoxide anion production compared with
      anti-CCL24 treated. These results suggest that CCL26 is a major eotaxin
      synthesized and released by alveolar epithelial cells and is involved in
      autoregulation of CCR3 receptors and other eotaxins. This CCL26-CCR3 ligand
      receptor system may be an attractive target for development of therapeutics that
      limits progress of inflammation in airway disease.

PMID- 15863445
TI  - Photosynthetic redox control of nuclear gene expression.
AB  - Chloroplasts contain 3000-4000 different proteins but only a small subset of them
      is encoded in the plastid genome while the majority is encoded in the nucleus.
      Expression of these genes therefore requires a high degree of co-ordination
      between nucleus and chloroplast. This is achieved by a bilateral information
      exchange between both compartments including nucleus-to-plastid (anterograde) and
      plastid-to-nucleus (retrograde) signals. The latter represent a functional
      feedback control which couples the expression of nuclear encoded plastid proteins
      to the actual functional state of the organelle. The efficiency of photosynthesis
      is a very important parameter in this context since it is influenced by many
      environmental conditions and therefore represents a sensor for the residing
      environment. Components of the photosynthetic electron transport chain exhibit
      significant changes in their reduction/oxidation (redox) state depending on the
      photosynthetic electron flow and therefore serve as signalling parameters which
      report environmental influences on photosynthesis. Such redox signals control
      chloroplast and nuclear gene expression events and play an important role in the
      co-ordination of both genetic compartments. It is discussed here which
      photosynthetic parameters are known to control nuclear gene expression, how these
      signals are transduced toward the nucleus, and how they interact with other
      plastid retrograde signals and cytosolic light perception systems.

PMID- 15863446
TI  - Redox regulation of carbon storage and partitioning in response to light and
      sugars.
AB  - Redox signals generated by the photosynthetic electron transport chain are known
      to be involved in regulating the Calvin cycle, ATP synthesis, and NADPH export
      from chloroplasts in response to light. The signal cascade involves transfer of
      electrons from photosystem I via the ferredoxin-thioredoxin system to target
      enzymes that are activated by reduction of regulatory disulphide bonds. The
      purpose of this review is to discuss recent findings showing that this concept
      can be extended to the regulation of carbon storage and partitioning in plants.
      Starch is the major carbon store in plants, and ADP-glucose pyrophosphorylase
      (AGPase) is the key regulatory enzyme of starch synthesis in the plastid. It has
      been shown that AGPase from potato tubers is subject to post-translational redox
      modification, and here experimental data will be provided showing that the
      isozyme from pea leaf chloroplasts is activated by reduced thioredoxin f or m in
      a similar way. Recent reports will be summarized providing in planta evidence
      that this mechanism regulates storage starch synthesis in response to light and
      sugars. Post-translational redox activation of AGPase in response to sugars is
      part of a signalling mechanism linking the rate of starch synthesis to the
      availability of carbon in diverse plant tissues. Some of the components of the
      signalling pathway reporting changes in the cytosolic sugar status to the plastid
      have been postulated, but detailed work is in progress to confirm the exact mode
      of action. Recent evidence will be discussed showing that key enzymes of de novo
      fatty acid synthesis (acetyl-CoA carboxylase) and ammonium assimilation
      (glutamine synthetase and glutamine:oxoglutarate amino transferase) are regulated
      by reversible disulphide-bond formation similar to AGPase. Redox regulation is
      proposed to be the preferred strategy of plastidial enzymes to regulate various
      metabolic processes such as carbon fixation, starch metabolism, lipid synthesis,
      and amino acid synthesis in response to physiological and environmental inputs.

PMID- 15863447
TI  - Pathogen-induced expression of a cecropin A-melittin antimicrobial peptide gene
      confers antifungal resistance in transgenic tobacco.
AB  - Expression of defensive genes from a promoter that is specifically activated in
      response to pathogen invasion is highly desirable for engineering disease
      resistant plants. A plant transformation vector was constructed with
      transcriptional fusion between the pathogen-responsive win3.12T promoter from
      poplar and the gene encoding the novel cecropin A-melittin hybrid peptide (CEMA)
      with strong antimicrobial activity. This promoter-transgene combination was
      evaluated in transgenic tobacco (Nicotiana tabacum L. cv. Xanthi) for enhanced
      plant resistance against a highly virulent pathogenic fungus Fusarium solani.
      Transgene expression in leaves was strongly increased after fungal infection or
      mechanical wounding, and the accumulation of CEMA transcripts was found to be
      systemic and positively correlated with the number of transgene insertions. A
      simple and efficient in vitro regeneration bioassay for preliminary screening of
      transgenic lines against pathogenic fungi was developed. CEMA had strong
      antifungal activity in vitro, inhibiting conidia germination at concentrations
      that were non-toxic to tobacco protoplasts. Most importantly, the expression
      level of the CEMA peptide in vivo, regulated by the win3.12T promoter, was
      sufficient to confer resistance against F. solani in transgenic tobacco. The
      antifungal resistance of plants with high CEMA expression was strong and
      reproducible. In addition, leaf tissue extracts from transgenic plants
      significantly reduced the number of fungal colonies arising from germinated
      conidia. Accumulation of CEMA peptide in transgenic tobacco had no deleterious
      effect on plant growth and development. This is the first report showing the
      application of a heterologous pathogen-inducible promoter to direct the
      expression of an antimicrobial peptide in plants, and the feasibility of this
      approach to provide disease resistance in tobacco and, possibly, other crops.

PMID- 15863448
TI  - Molecular characterization and systemic induction of single-chain ribosome
      inactivating proteins (RIPs) in sugar beet (Beta vulgaris) leaves.
AB  - Sugar beet (Beta vulgaris L.) leaves contain virus-inducible type 1 (single
      chain) ribosome-inactivating proteins that have been named beetins. The
      structural and functional characterization, the cellular location, and the
      potential role of beetins as antiviral agents are reported here. Beetins are
      formed of a single polypeptide chain with a varying degree of glycosylation and
      strongly inhibited in vitro protein synthesis in rabbit reticulocyte lysates
      (IC50=1.15 ng ml(-1)) and a Vicia sativa L. cell-free system (IC50=68 ng ml(-1))
      through the single depurination of the large rRNA. Beetins trigger the
      multidepurination of tobacco mosaic virus (TMV) genomic RNA which underwent
      extensive degradation upon treatment with acid aniline. Beetins are extracellular
      proteins that were recovered from the apoplastic fluid. Induction of sugar beet
      RIPs with either H2O2 or artichoke mottled crinkle virus (AMCV) was observed in
      leaves distant from the site of application of such elicitors. The external
      application of purified beetin to sugar leaves prevented infection by AMCV which
      supports the preliminary hypothesis that beetins could be involved in plant
      systemic acquired resistance subjected to induction by phytopathogens.

PMID- 15863449
TI  - Chloroplasts as source and target of cellular redox regulation: a discussion on
      chloroplast redox signals in the context of plant physiology.
AB  - During the evolution of plants, chloroplasts have lost the exclusive genetic
      control over redox regulation and antioxidant gene expression. Together with many
      other genes, all genes encoding antioxidant enzymes and enzymes involved in the
      biosynthesis of low molecular weight antioxidants were transferred to the
      nucleus. On the other hand, photosynthesis bears a high risk for photo-oxidative
      damage. Concomitantly, an intricate network for mutual regulation by anthero- and
      retrograde signals has emerged to co-ordinate the activities of the different
      genetic and metabolic compartments. A major focus of recent research in
      chloroplast regulation addressed the mechanisms of redox sensing and signal
      transmission, the identification of regulatory targets, and the understanding of
      adaptation mechanisms. In addition to redox signals communicated through
      signalling cascades also used in pathogen and wounding responses, specific
      chloroplast signals control nuclear gene expression. Signalling pathways are
      triggered by the redox state of the plastoquinone pool, the thioredoxin system,
      and the acceptor availability at photosystem I, in addition to control by
      oxolipins, tetrapyrroles, carbohydrates, and abscisic acid. The signalling
      function is discussed in the context of regulatory circuitries that control the
      expression of antioxidant enzymes and redox modulators, demonstrating the
      principal role of chloroplasts as the source and target of redox regulation.

PMID- 15863450
TI  - Role of cathepsins and cystatins in patients with recurrent miscarriage.
AB  - In the implantation, trophoblasts penetrate maternal decidua by secreting
      proteases. It has been reported that cathepsins are highly expressed in the mouse
      villi, and play an important role in normal embryonal growth and decidualization.
      In this study, we evaluated cathepsins and their endogenous inhibitors,
      cystatins, in tissue and serum of patients with recurrent miscarriage. Decidua
      and villi were surgically collected from 22 patients and 12 healthy women.
      Immunohistochemistry was performed with antibodies against cathepsins, stefin A
      (cystatin A), stefin B (cystatin B) and cystatin C. The concentrations of
      cathepsins, stefins and cystatin C were measured by Enzyme-linked immunosorbent
      assay. In addition, we measured the serum level of cystatin C in 85 Japanese
      women with recurrent miscarriage. Staining of cathepsin B, D, H, L, stefin B and
      cystatin C was observed in the cytoplasm of epithelial cells in decidua. Stefin A
      was expressed on the surface of the trophoblast. The concentration of cathepsin B
      and H in patients' decidua was significantly higher than in control individuals.
      The serum level of cystatin C was significantly lower in patients than in control
      individuals. Our findings suggest that the regulation of the cathepsin-cystatin
      system may play an important role in patients with recurrent miscarriage.

PMID- 15863451
TI  - Cytoplasmic fragmentation in activated eggs occurs in the cytokinetic phase of
      the cell cycle, in lieu of normal cytokinesis, and in response to cytoskeletal
      disorder.
AB  - The timing of cytoplasmic fragmentation in relation to the cell cycle was studied
      in mature oocytes and early cleavage stages using mouse oocytes and embryos as
      experimental models. The central approach was to remove the nuclear apparatus, in
      whole or in part, from non-activated and activated oocytes and early embryos, and
      follow their response during subsequent culture in vitro. Oocytes arrested in
      metaphase of the second meiotic division did not fragment following complete
      removal of the meiotic apparatus, provided they were not subsequently activated.
      Exposure of spindle-chromosome-complex-depleted oocytes to activation conditions
      immediately after enucleation led to fragmentation, although not until control
      embryos entered first mitosis. Delaying activation until 24 h post-enucleation
      led to earlier fragmentation. Enucleation of normally fertilized or artificially
      activated oocytes after emission of the second polar body also led to
      fragmentation coinciding with the first mitosis in nucleated control embryos.
      However, if artificially activated oocytes were prevented from completing second
      meiosis, by exposure to cytochalasin, and then enucleated, this universal wave of
      fragmentation was preceded in some cytoplasts by limited fragmentation after just
      a few hours in culture, and coinciding with completion of meiosis II in nucleated
      oocytes. Fragmentation also occurred in the second mitotic cell cycle, but it was
      limited to blastomeres of fertilized oocytes that were enucleated in late
      interphase. These results indicate that fragmentation in oocytes and early
      embryos, though seemingly uncoordinated, is a precisely timed event that occurs
      only in mitotically active cells, during the cytokinetic phase of the cell cycle,
      in lieu of normal cytokinesis, and in response to altered cytoskeletal
      organization.

PMID- 15863452
TI  - Optical measurements reveal nature of intercellular coupling across ventricular
      wall.
AB  - Previously, we showed that intercellular uncoupling through gap junctions is an
      important mechanism for maintaining transmural heterogeneities of repolarization
      that are responsible for ventricular arrhythmias in disease states such as heart
      failure. However, rotational anisotropy between transmural muscle layers also may
      influence coupling. To determine the effect of rotational anisotropy on
      transmural coupling, we developed a numerical three-dimensional model of passive
      cardiac tissue in which rotational anisotropy was varied in a controlled fashion.
      Simulations of optical mapping demonstrated that spatial averaging produced a
      voltage decay in space best fit by a single decaying exponential compared with
      the theoretically predicted decay. As fiber orientation varied by 90 degrees with
      respect to the transmural surface, the effective transmural space constant
      (lambda(TM)) changed by only 0.31% in simulations. In contrast, reducing
      intercellular conductivity by 24% decreased lambda(TM) by 7.7%. In the canine
      wedge preparation (n = 5), lambda measured by optical mapping of the epicardial
      and subepicardial surface was similar transverse (lambda(TV) = 0.73 +/- 0.10 mm)
      and transmural (lambda(TM) = 0.70 +/- 0.08 mm) to subepicardial fibers. We
      confirmed previous findings that lambda(TM) in subepicardial layers was
      significantly reduced by 14 +/- 2% compared with deeper layers of myocardium,
      providing evidence for transmural uncoupling in the epicardial-midmyocardial
      interface. These data establish the theoretical and experimental basis for
      measuring intercellular coupling between muscle layers spanning the ventricular
      wall with optical mapping techniques. Furthermore, this study demonstrates that
      transmural uncoupling at the epicardial-midmyocardial interface may be
      attributable to heterogeneous expression of cardiac gap junctions and not
      rotational anisotropy.

PMID- 15863453
TI  - Baroreflex control of muscle sympathetic nerve activity in postural orthostatic
      tachycardia syndrome.
AB  - Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive
      tachycardia during orthostasis. To test the hypothesis that patients with POTS
      have decreased sympathetic neural responses to baroreflex stimuli, we measured
      heart rate (HR) and muscle sympathetic nerve activity (MSNA) responses to three
      baroreflex stimuli including vasoactive drug boluses (modified Oxford technique),
      Valsalva maneuver, and head-up tilt (HUT) in POTS patients and healthy control
      subjects. The MSNA response to the Valsalva maneuver was significantly greater in
      the POTS group (controls, 26 +/- 7 vs. POTS, 48 +/- 6% of baseline MSNA/mmHg; P =
      0.03). POTS patients also had an exaggerated MSNA response to 30 degrees HUT
      (controls, 123 +/- 24 vs. POTS, 208 +/- 30% of baseline MSNA; P = 0.03) and
      tended to have an exaggerated response to 45 degrees HUT (controls, 137 +/- 27
      vs. POTS, 248 +/- 58% of baseline MSNA; P = 0.10). Sympathetic baroreflex
      sensitivity calculated during administration of the vasoactive drug boluses also
      tended to be greater in the POTS patients; however, this did not reach
      statistical significance (P = 0.15). Baseline MSNA values during supine rest were
      not different between the groups (controls, 23 +/- 4 vs. POTS, 16 +/- 5
      bursts/100 heartbeats; P = 0.30); however, resting HR was significantly higher in
      the POTS group (controls, 58 +/- 3 vs. POTS, 82 +/- 4 beats/min; P = 0.0001). Our
      results suggest that POTS patients have exaggerated MSNA responses to baroreflex
      challenges compared with healthy control subjects, although resting supine MSNA
      values did not differ between the groups.

PMID- 15863454
TI  - Arachidonic acid metabolites, hydrogen peroxide, and EDHF in cerebral arteries.
AB  - We tested the hypotheses that EDHF in rat middle cerebral arteries (MCAs)
      involves 1) metabolism of arachidonic acid through the epoxygenase pathway, 2)
      metabolism of arachidonic acid through the lipoxygenase pathway, or 3) reactive
      oxygen species. EDHF-mediated dilations were elicited in isolated and pressurized
      rat MCAs by activation of endothelial P2Y(2) receptors with either UTP or ATP.
      All studies were conducted after the inhibition of nitric oxide synthase and
      cyclooxygenase with N(omega)-nitro-l-arginine methyl ester (10 microM) and
      indomethacin (10 microM), respectively. The inhibition of epoxygenase with
      miconazole (30 microM) did not alter EDHF dilations to UTP, whereas the
      structurally different epoxygenase inhibitor N-methylsulfonyl-6-(2
      propargyloxyphenyl)hexanoic acid (20 or 40 microM) only modestly inhibited EDHF
      at the highest concentration of UTP. An antagonist of epoxyeicosatrienoic acids,
      14,15-epoxyeicosa-5(Z)-enoic acid, had no effect on EDHF dilations to UTP.
      Chronic inhibition of epoxygenase in the rat with 1-aminobenzotriazol (50 mg/kg
      twice daily for 5 days) did not alter EDHF dilations. The inhibition of the
      lipoxygenase pathway with either 10 microM baicalein or 10 microM
      nordihydroguaiaretic acid produced no major inhibitory effects on EDHF dilations.
      The combination of superoxide dismutase (200 U/ml) and catalase (140 U/ml) had no
      effect on EDHF dilations. Neither tiron (10 mM), a cell-permeable scavenger of
      reactive oxygen species, nor deferoxamine (1 or 10 mM), an iron chelator that
      blocks the formation of hydroxyl radicals, altered EDHF dilations in rat MCAs. We
      conclude that EDHF dilations in the rat MCA do not involve the epoxygenase
      pathway, lipoxygenase pathway, or reactive oxygen species including H(2)O(2).

PMID- 15863455
TI  - Validation of echocardiographic and Doppler indexes of left ventricular
      relaxation in adult hypertensive and normotensive rats.
AB  - This study was performed to validate echocardiographic and Doppler techniques for
      the assessment of left ventricular (LV) diastolic function in spontaneously
      hypertensive rats (SHR) and normotensive Wistar rats. In 11 Wistar rats and 20
      SHR, we compared 51 sets of invasive and Doppler LV diastolic indexes.
      Noninvasive indexes of LV relaxation were related to the minimal rate of pressure
      decline (-dP/dt(min)), particularly isovolumic relaxation time (IVRT), the Tei
      index, the early velocity of the mitral annulus (E(m)) using Doppler tissue
      imaging, and early mitral flow propagation velocity using M-mode color (r = 0.28
      0.56 and P < 0.05-0.0001). When the role of systolic load was considered, the
      correlation between Doppler indexes of LV diastolic function and relaxation rate
      [(-dP/dt(min))/LV systolic pressure] improved (r = 0.48-0.86 and P = 0.004
      0.0001, respectively). Similarly, Doppler indexes of LV diastolic function and
      the time constant of isovolumic LV relaxation (tau) correlated well (r = 0.50
      0.84 and P = 0.0002-0.0001, respectively). In addition, eight SHR and eight
      Wistar rats were compared; their LV end-diastolic diameters were similar, whereas
      the SHR LV mass was greater. Furthermore, IVRT and Tei index were significantly
      higher and E(m) was lower in SHR. Moreover, tau was higher in SHR, demonstrating
      impaired LV relaxation. In conclusion, LV relaxation can be assessed reliably
      using echocardiographic and Doppler techniques, and, using these indexes,
      impaired relaxation was demonstrated in SHR.

PMID- 15863456
TI  - Myogenic contraction in rat skeletal muscle arterioles: smooth muscle membrane
      potential and Ca(2+) signaling.
AB  - The present studies examined relationships between intraluminal pressure,
      membrane potential (E(m)), and myogenic tone in skeletal muscle arterioles. Using
      pharmacological interventions targeting Ca(2+) entry/release mechanisms, these
      studies also determined the role of Ca(2+) pathways and E(m) in determining
      steady-state myogenic constriction. Studies were conducted in isolated and
      cannulated arterioles under zero flow. Increasing intraluminal pressure (0-150
      mmHg) resulted in progressive membrane depolarization (-55.3 +/- 4.1 to -29.4 +/-
      0.7 mV) that exhibited a sigmoidal relationship between extent of myogenic
      constriction and E(m). Thus, despite further depolarization, at pressures >70
      mmHg, little additional vasoconstriction occurred. This was not due to an
      inability of voltage-operated Ca(2+) channels to be activated as KCl (75 mM)
      evoked depolarization and vasoconstriction at 120 mmHg. Nifedipine (1 microM) and
      cyclopiazonic acid (30 microM) significantly attenuated established myogenic
      tone, whereas inhibition of inositol 1,4,5-trisphosphate-mediated Ca(2+)
      release/entry by 2-aminoethoxydiphenylborate (50 microM) had little effect.
      Combinations of the Ca(2+) entry blockers with the sarcoplasmic reticulum (SR)
      inhibitor caused a total loss of tone, suggesting that while depolarization
      mediated Ca(2+) entry makes a significant contribution to myogenic tone, an
      interaction between Ca(2+) entry and SR Ca(2+) release is necessary for
      maintenance of myogenic constriction. In contrast, none of the agents, in
      combination or alone, altered E(m), demonstrating the downstream role of Ca(2+)
      mobilization relative to changes in E(m). Large-conductance Ca(2+)-activated K(+)
      channels modulated E(m) to exert a small effect on myogenic tone, and consistent
      with this, skeletal muscle arterioles appeared to show an inherently steep
      relationship between E(m) and extent of myogenic tone. Collectively, skeletal
      muscle arterioles exhibit complex relationships between E(m), Ca(2+)
      availability, and myogenic constriction that impact on the tissue's physiological
      function.

PMID- 15863457
TI  - Vasoactive prostanoids are generated from arachidonic acid by COX-1 and COX-2 in
      the mouse.
AB  - Generation of vasoactive prostanoids from arachidonic acid by cyclooxygenase
      (COX)-1 and COX-2 was investigated in anesthetized mice. Intravenous injections
      of the prostanoid precursor arachidonic acid increased pulmonary arterial
      pressure and decreased systemic arterial pressure. Pulmonary pressor and systemic
      depressor responses were attenuated by SC-560 and nimesulide, inhibitors of COX-1
      and COX-2, in doses that did not alter responses to injected prostanoids.
      Pulmonary pressor responses to arachidonic acid were blocked and a depressor
      response was unmasked, whereas systemic depressor responses were not altered, by
      a thromboxane receptor antagonist. Pulmonary and systemic pressor responses to
      angiotensin II injections and systemic pressor responses to angiotensin II
      infusion were not modified by COX-1 or COX-2 inhibitors but were attenuated by
      losartan. Systemic depressor responses to arachidonic acid were smaller in COX-1
      and COX-2 knockout mice, whereas responses to angiotensin II, norepinephrine, U
      46619, endothelin-1, and PGE(1) were not different in COX-1 and COX-2 knockout
      and wild-type control mice. These results suggest that vasoactive prostanoids
      with pulmonary pressor and systemic vasodepressor activity are formed by COX-1
      and COX-2 and are consistent with Western blot analysis and immunostaining
      showing the presence of COX-1 and COX-2. These data suggest that thromboxane A(2)
      (TxA(2)) is formed from the precursor by COX-1 and COX-2 in the lung and are in
      agreement with immunofluorescence studies showing thromboxane synthase. The
      present data suggest that COX-1- or COX-2-derived prostanoids do not modulate
      responses to angiotensin II or other vasoactive agents and that prostanoid
      responses are similar in CD-1 and C57BL/6 and in male and female mice.

PMID- 15863458
TI  - Mitral tetrahedron as a geometrical surrogate for chronic ischemic mitral
      regurgitation.
AB  - The present study tests the hypothesis that a mitral tetrahedron (MT) is a useful
      geometrical surrogate for assessment of chronic ischemic mitral regurgitation
      (CIMR). Fifty-eight subjects were divided into three groups on the basis of left
      ventricular ejection fraction (LVEF) and the presence or absence of CIMR: LVEF >
      or =0.5 and negative CIMR (group 1, n = 28), LVEF <0.5 and negative CIMR (group
      2, n = 12), and LVEF <0.5 and positive CIMR (group 3, n = 18). MT was defined by
      its four vertices at the anterior annulus, posterior annulus, and medial and
      lateral papillary muscle roots, determined by MRI at peak systole. The results
      showed no clear cutoff values of MT parameters between groups 2 and 1. In
      contrast, all MT indexes were significantly different between groups 3 and 2 (P <
      0.05), and significant cutoff values differentiated the two groups. A scoring
      system employing parameters of the whole MT confirmed the absence of CIMR with
      total edge length index <268 mm/BSA(1/3), total surface area index <2,528
      mm(2)/BSA(2/3), and volume index <5,089 mm(3)/BSA (where BSA is body surface
      area). The sensitivity, specificity, and positive and negative predictive values
      were 1.00. This preliminary study demonstrates that MT might serve as a good
      geometrical surrogate for assessing CIMR. The derived geometrical criteria of MT
      may be useful in surgical correction of CIMR.

PMID- 15863459
TI  - Chronic xanthine oxidase inhibition prevents myofibrillar protein oxidation and
      preserves cardiac function in a transgenic mouse model of cardiomyopathy.
AB  - Heart failure is a clinical syndrome associated with elevated levels of oxygen
      derived free radicals. Xanthine oxidase activity is believed to be one source of
      reactive oxygen species in the failing heart. Interventions designed to reduce
      oxidative stress are believed to have significant therapeutic potential in heart
      failure. This study tested the hypothesis that xanthine oxidase activity would be
      elevated in a mouse model of dilated cardiomyopathy and evaluated the effect of
      chronic oral allopurinol, an inhibitor of xanthine oxidase, on contractility and
      progressive ventricular dilation in these mice. Nontransgenic and transgenic mice
      containing a troponin I truncation were treated with oral allopurinol from 2-4 mo
      of age. Myocardial xanthine oxidase activity was threefold higher in untreated
      transgenic mice compared with nontransgenic mice. Analyses of myofilament
      proteins for modification of carbonyl groups demonstrated myofibrillar protein
      damage in untreated transgenic mice. Treatment with allopurinol for 2 mo
      suppressed xanthine oxidase activity and myofibrillar protein oxidation.
      Allopurinol treatment also alleviated ventricular dilation and preserved
      shortening fraction in the transgenic animals. In addition, cardiac muscle twitch
      tension was preserved to 70% of nontransgenic levels in allopurinol-treated
      transgenic mice, a significant improvement over untreated transgenic mice. These
      findings indicate that chronic inhibition of xanthine oxidase can alter the
      progression of heart failure in dilated cardiomyopathy.

PMID- 15863460
TI  - Proinflammatory phenotype of vascular smooth muscle cells: role of efficient Toll
      like receptor 4 signaling.
AB  - Recent evidence supports a role of Toll-like receptor (TLR) signaling in the
      development of atherosclerotic lesions. In this study, we tested whether TLR4
      signaling promotes a proinflammatory phenotype in human and mouse arterial smooth
      muscle cells (SMC), characterized by increased cytokine and chemokine synthesis
      and increased TLR expression. Human arterial SMC were found to express mRNA
      encoding TLR4 and the TLR4-associated molecules MD-2 and CD14 but not TLR2 mRNA.
      Mouse aortic SMC, on the other hand, expressed both TLR2 and TLR4 mRNA
      constitutively. Human SMC derived from the coronary artery, but not those from
      the pulmonary artery, were found to express cell surface-associated CD14. Low
      concentrations (ng/ml) of Escherichia coli LPS, the prototypical TLR4 agonist,
      markedly stimulated extracellular regulated kinase 1/2 (ERK1/2) activity, induced
      release of monocyte-chemoattractant protein-1 (MCP-1) and interleukin (IL)-6, and
      stimulated IL-1alpha expression in human aortic SMC, and exogenous CD14 enhanced
      these effects. Expression of a dominant negative form of TLR4 in human SMC
      attenuated LPS-induced ERK1/2 and MCP-1 release. LPS was a potent inducer of NF
      kappaB activity, ERK1/2 phosphorylation, MCP-1 release, and TLR2 mRNA expression
      in wild-type mice but not in TLR4-signaling deficient mouse aortic SMC. These
      studies show that TLR4 signaling promotes a proinflammatory phenotype in vascular
      smooth muscle cells (VSMC) and suggest that VSMC may potentially play an active
      role in vascular inflammation via the release of chemokines, proinflammatory
      cytokines, and increased expression of TLR2.

PMID- 15863461
TI  - Dynamic cerebral autoregulation during brain activation paradigms.
AB  - Dynamic cerebral autoregulation (CA) describes the transient response of cerebral
      blood flow (CBF) to rapid changes in arterial blood pressure (ABP). We tested the
      hypothesis that the efficiency of dynamic CA is increased by brain activation
      paradigms designed to induce hemispheric lateralization. CBF velocity [CBFV;
      bilateral, middle cerebral artery (MCA)], ABP, ECG, and end-tidal Pco(2) were
      continuously recorded in 14 right-handed healthy subjects (21-43 yr of age), in
      the seated position, at rest and during 10 repeated presentations (30 s on-off)
      of a word generation test and a constructional puzzle. Nonstationarities were not
      found during rest or activation. Transfer function analysis of the ABP-CBFV
      (i.e., input-output) relation was performed for the 10 separate 51.2-s segments
      of data during activation and compared with baseline data. During activation, the
      coherence function below 0.05 Hz was significantly increased for the right MCA
      recordings for the puzzle tasks compared with baseline values (0.36 +/- 0.16 vs.
      0.26 +/- 0.13, P < 0.05) and for the left MCA recordings for the word paradigm
      (0.48 +/- 0.23 vs. 0.29 +/- 0.16, P < 0.05). In the same frequency range,
      significant increases in gain were observed during the puzzle paradigm for the
      right (0.69 +/- 0.37 vs. 0.46 +/- 0.32 cm.s(-1).mmHg(-1), P < 0.05) and left
      (0.61 +/- 0.29 vs. 0.45 +/- 0.24 cm.s(-1).mmHg(-1), P < 0.05) hemispheres and
      during the word tasks for the left hemisphere (0.66 +/- 0.31 vs. 0.39 +/- 0.15
      cm.s(-1).mmHg(-1), P < 0.01). Significant reductions in phase were observed
      during activation with the puzzle task for the right (-0.04 +/- 1.01 vs. 0.80 +/-
      0.86 rad, P < 0.01) and left (0.11 +/- 0.81 vs. 0.57 +/- 0.51 rad, P < 0.05)
      hemispheres and with the word paradigm for the right hemisphere (0.05 +/- 0.87
      vs. 0.64 +/- 0.59 rad, P < 0.05). Brain activation also led to changes in the
      temporal pattern of the CBFV step response. We conclude that transfer function
      analysis suggests important changes in dynamic CA during mental activation tasks.

PMID- 15863462
TI  - A novel model of cryoinjury-induced myocardial infarction in the mouse: a
      comparison with coronary artery ligation.
AB  - Mouse myocardial infarction (MI) models are frequently used research tools. The
      most commonly applied model is coronary artery ligation. However, coronary
      ligation often gives rise to apical aneurysmatic infarcts of variable size. Other
      infarct models include cryoinfarction, which produces reproducible infarcts of
      the anterior wall. Thus far, this model has not been extensively described in
      mice. Therefore, we developed a murine cryoinfarction model and compared it with
      coronary ligation. Studies were performed under isoflurane anesthesia with a
      follow-up of 4 and 8 wk. Cryoinfarction was induced using a 2- or 3-mm cryoprobe.
      Two-dimensional guided M-mode echocardiography was used to assess fractional
      shortening and left ventricular (LV) dimensions at baseline and end point. At end
      point, hemodynamics were assessed using a 1.4-Fr Millar catheter. Pressure
      diameter relations were constructed by combining echocardiography and hemodynamic
      data. Histological and morphometric analyses of infarct and remote areas were
      performed. At 4 wk, 3-mm cryoinfarction resulted in decreased LV fractional
      shortening as well as decreased global LV contractility and relaxation, which was
      comparable with coronary ligation. No adverse remodeling was observed at this
      time point, in contrast with the ligation model. However, progressive LV
      remodeling occured between 4 and 8 wk after cryoinfarction with a further decline
      in hemodynamic parameters and LV pump function. Histologically, cryoinfarction
      resulted in highly reproducible, transmural, cone-shaped infarcts with
      reperfusion at the macrovascular level. These results indicate that the
      cryoinfarction model represents the anterior myocardial infarct with modest
      adverse remodeling and may thus be representative for infarcts encountered in
      clinical practice.

PMID- 15863463
TI  - Acute ethanol exposure impairs angiogenesis and the proliferative phase of wound
      healing.
AB  - Acute ethanol exposure represents an increased risk factor for morbidity and
      mortality associated with surgical or traumatic injury. Despite clinical
      observations suggesting that ethanol exposure before injury alters tissue repair
      processes, little direct evidence about the mechanism by which ethanol affects
      the wound healing process is available. In this study, excisional wounds from
      female BALB/c mice with or without circulating ethanol levels of 100 mg/dl were
      used to assess wound closure, angiogenesis, and collagen content. Ethanol
      exposure resulted in a significant but transient delay in wound closure at day 2
      postwounding (28 +/- 4% vs. 17 +/- 1%). In addition, total collagen content was
      significantly reduced by up to 37% in wounds from ethanol-treated mice compared
      with controls. The most significant effect of ethanol exposure on wounds was on
      vascularity because angiogenesis was reduced by up to 61% in wounds from ethanol
      treated mice. The reduction in vessel density occurred despite near-normal levels
      of proangiogenic factors VEGF and FGF-2, suggesting a direct effect of ethanol
      exposure on endothelial cell function. Further evidence for a direct effect was
      observed in an in vitro angiogenesis assay because the exposure of endothelial
      cells to ethanol reduced angiogenic responsiveness to just 8.33% of control in a
      cord-forming assay. These studies provide novel information regarding the effect
      of a single dose of ethanol on multiple parameters of the wound healing process
      in vivo and suggest a potential mechanism by which ethanol impairs healing after
      traumatic injury.

PMID- 15863464
TI  - Dilated cardiomyopathy in Erb-b4-deficient ventricular muscle.
AB  - The neuregulin receptor tyrosine kinase Erb-b4, initially linked to early cardiac
      development, is shown here to play a critical role in adult cardiac function. In
      wild-type mice, Erb-b4 protein localized to Z lines and to intercalated disks,
      suggesting a role in subcellular and intercellular communications of
      cardiomyocytes. Conditional inactivation of erb-b4 in ventricular muscle cells
      led to a severe dilated cardiomyopathy, characterized by thinned ventricular
      walls with eccentric hypertrophy, reduced contractility, and delayed conduction.
      This cardiac dysfunction may account for premature death in adult erb-b4-knockout
      mice. This study establishes a critical role for Erb-b4 in the maintenance of
      normal postnatal cardiac structure and function.

PMID- 15863465
TI  - Effects of elastin haploinsufficiency on the mechanical behavior of mouse
      arteries.
AB  - Supravalvular aortic stenosis (SVAS) is associated with decreased elastin and
      altered arterial mechanics. Mice with a single deletion in the elastin gene
      (ELN(+/-)) are models for SVAS. Previous studies have shown that elastin
      haploinsufficiency in these mice causes hypertension, decreased arterial
      compliance, and changes in arterial wall structure. Despite these differences,
      ELN(+/-) mice have a normal life span, suggesting that the arteries remodel and
      adapt to the decreased amount of elastin. To test this hypothesis, we performed
      in vitro mechanical tests on abdominal aorta, ascending aorta, and left common
      carotid artery from ELN(+/-) and wild-type (C57BL/6J) mice. We compared the
      circumferential and longitudinal stress-stretch relationships and residual
      strains. The circumferential stress-stretch relationship is similar between
      genotypes and changes <3% with longitudinal stretch at lengths within 10% of the
      in vivo value. At mean arterial pressure, the circumferential stress in the
      ascending aorta is higher in ELN(+/-) than in wild type. Although arterial
      pressures are higher, the increased number of elastic lamellae in ELN(+/-)
      arteries results in similar tension/lamellae compared with wild type. The
      longitudinal stress-stretch relationship is similar between genotypes for most
      arteries. Compared with wild type, the in vivo longitudinal stretch is lower in
      ELN(+/-) abdominal and carotid arteries and the circumferential residual strain
      is higher in ELN(+/-) ascending aorta. The increased circumferential residual
      strain brings the transmural strain distribution in ELN(+/-) ascending aorta
      close to wild-type values. The mechanical behavior of ELN(+/-) arteries is likely
      due to the reduced elastin content combined with adaptive remodeling during
      vascular development.

PMID- 15863466
TI  - Nationwide age references for sitting height, leg length, and sitting
      height/height ratio, and their diagnostic value for disproportionate growth
      disorders.
AB  - AIMS: To obtain age references for sitting height (SH), leg length (LL), and SH/H
      ratio in the Netherlands; to evaluate how SH standard deviation score (SDS), LL
      SDS, SH/H SDS, and SH/LL SDS are related to height SDS; and to study the
      usefulness of height corrected SH/H cut-off lines to detect Marfan syndrome and
      hypochondroplasia. METHODS: Cross-sectional data on height and sitting height
      were collected from 14,500 children of Dutch origin in the age range 0-21 years.
      Reference SD charts were constructed by the LMS method. Correlations were
      analysed in three age groups. SH/H data from patients with Marfan syndrome and
      genetically confirmed hypochondroplasia were compared with height corrected SH/H
      references. RESULTS: A positive association was observed between H SDS, SH SDS,
      and LL SDS in all age groups. There was a negative correlation between SH/H SDS
      and height SDS. In short children with a height SDS <-2 SDS, a cut-off limit of
      +2.5 SD leads to a more acceptable percentage of false positive results. In
      exceptionally tall children, a cut-off limit of -2.2 SDS can be used.
      Alternatively, a nomogram of SH/H SDS versus H SDS can be helpful. The
      sensitivity of the height corrected cut-off lines for hypochondroplasia was 80%
      and for Marfan syndrome only 30%. CONCLUSIONS: In exceptionally short or tall
      children, the dependency of the SH/H ratio (SDS) on height SDS has to be taken
      into consideration in the evaluation of body proportions. The sensitivity of the
      cut-off lines for hypochondroplasia is fair.

PMID- 15863467
TI  - Systematic review of prevalence studies of autism spectrum disorders.
AB  - AIM: To quantitatively examine the influence of study methodology and population
      characteristics on prevalence estimates of autism spectrum disorders. METHODS:
      Electronic databases and bibliographies were searched and identified papers
      evaluated against inclusion criteria. Two groups of studies estimated the
      prevalence of typical autism and all autism spectrum disorders (ASD). The extent
      of variation among studies and overall prevalence were estimated using meta
      analysis. The influence of methodological factors and population characteristics
      on estimated prevalence was investigated using meta-regression and summarised as
      odds ratios (OR). RESULTS: Forty studies met inclusion criteria, of which 37
      estimated the prevalence of typical autism, and 23 the prevalence of all ASD. A
      high degree of heterogeneity among studies was observed. The overall random
      effects estimate of prevalence across studies of typical autism was 7.1 per
      10,000 (95% CI 1.6 to 30.6) and of all ASD was 20.0 per 10,000 (95% CI 4.9 to
      82.1). Diagnostic criteria used (ICD-10 or DSM-IV versus other; OR = 3.36, 95% CI
      2.07 to 5.46), age of the children screened (OR = 0.91 per year, 95% CI 0.83 to
      0.99), and study location (e.g. Japan versus North America; OR = 3.60, 95% CI
      1.73 to 7.46) were all significantly associated with prevalence of typical
      autism. Diagnostic criteria, age of the sample, and urban or rural location were
      associated with estimated prevalence of all ASD. CONCLUSIONS: Sixty one per cent
      of the variation in prevalence estimates of typical autism was explained by these
      models. Diagnostic criteria used, age of children screened, and study location
      may be acting as proxies for other study characteristics and require further
      investigation.

PMID- 15863468
TI  - Effects of probiotics on atopic dermatitis: a randomised controlled trial.
AB  - BACKGROUND: The aim of the study was to investigate the effects of probiotics on
      moderate or severe atopic dermatitis (AD) in young children. METHODS: Fifty six
      children aged 6-18 months with moderate or severe AD were recruited into a
      randomised double blind placebo controlled trial in Perth, Western Australia; 53
      children completed the study. The children were given a probiotic
      (1x10(9)Lactobacillus fermentum VRI-033 PCC; Probiomics) or an equivalent volume
      of placebo, twice daily for 8 weeks. A final assessment at 16 weeks was
      performed. RESULTS: The main outcome measures were severity and extent of AD at
      the end of the study, as measured by the Severity Scoring of Atopic Dermatitis
      (SCORAD) index. The reduction in the SCORAD index over time was significant in
      the probiotic group (p = 0.03) but not the placebo group. Significantly more
      children receiving probiotics (n = 24, 92%) had a SCORAD index that was better
      than baseline at week 16 compared with the placebo group (n = 17, 63%) (p =
      0.01). At the completion of the study more children in the probiotic group had
      mild AD (n = 14, 54%) compared to the placebo group (n = 8, 30%). CONCLUSION:
      Supplementation with probiotic L fermentum VRI-003 PCC is beneficial in improving
      the extent and severity of AD in young children with moderate or severe disease.

PMID- 15863469
TI  - Reproductive allocation of biomass and nitrogen in annual and perennial
      Lesquerella crops.
AB  - BACKGROUND AND AIMS: The use of perennial crops could contribute to increase
      agricultural sustainability. However, almost all of the major grain crops are
      herbaceous annuals and opportunities to replace them with more long-lived
      perennials have been poorly explored. This follows the presumption that the
      perennial life cycle is associated with a lower potential yield, due to a reduced
      allocation of biomass to grains. The hypothesis was tested that allocation to
      perpetuation organs in the perennial L. mendocina would not be directly related
      to a lower allocation to seeds. * METHODS: Two field experiments were carried on
      with the annual Lesquerella fendleri and the iteroparous perennial L. mendocina,
      two promising oil-seed crops for low-productivity environments, subjected to
      different water and nitrogen availability. * KEY RESULTS: Seed biomass allocation
      was similar for both species, and unresponsive to water and nitrogen
      availability. Greater root and vegetative shoot allocation in the perennial was
      counterbalanced by a lower allocation to other reproductive structures compared
      with the annual Lesquerella. Allometric relationships revealed that allocation
      differences between the annual and the perennial increased linearly with plant
      size. The general allocation patterns for nitrogen did not differ from those of
      biomass. However, nitrogen concentrations were higher in the vegetative shoot and
      root of L. mendocina than of L. fendleri but remained stable in seeds of both
      species. * CONCLUSIONS: It is concluded that vegetative organs are more
      hierarchically important sinks in L. mendocina than in the annual L. fendleri,
      but without disadvantages in seed hierarchy.

PMID- 15863470
TI  - The CCR5-delta32 mutation: impact on disease outcome in individuals with
      hepatitis C infection from a single source.
AB  - BACKGROUND AND AIMS: Chemokines are small polypeptides, a major function of which
      is lymphocyte recruitment and trafficking. The aim of this study was to assess
      the involvement of inherited variations in CCR2, CCR5, and the ligand RANTES in
      determining disease outcome in hepatitis C virus (HCV) infected individuals.
      METHODS: A total of 283 women, all exposed to HCV genotype 1b from a single
      donor, and including those who had spontaneously cleared the virus and those
      chronically infected, were genotyped for CCR2, CCR5, and RANTES polymorphisms.
      The frequencies of these polymorphisms were then compared with disease activity
      and severity. RESULTS: CCR5, CCR2, and RANTES genotypes were compared with HCV
      polymerase chain reaction (PCR) status, alanine aminotransferase levels, and
      liver histology. There was no significant relationship between CCR2 or RANTES
      polymorphisms and disease outcome or severity. However, CCR5delta32 heterozygotes
      were more likely to have spontaneous clearance of the virus than those without
      the mutation (42% PCR negative v 28.3% negative; p = 0.044, odds ratio 1.83 (95%
      confidence interval 1.1-3.6)). Among the subgroup of DRB1*03011 negative
      individuals, previously found to be associated with more severe inflammation, the
      difference in histological inflammatory score (CCR5WT/WT = 4.9 v CCR5delta32/WT =
      3.53; p = 0.043) was significant. CONCLUSION: Heterozygosity for CCR5delta32 was
      shown to be significantly associated with spontaneous hepatitis C viral clearance
      and with significantly lower hepatic inflammatory scores in subgroups within this
      cohort. Both controls and the HCV population had similar heterozygosity
      frequencies.

PMID- 15863471
TI  - Transactivation of the epidermal growth factor receptor by cag+ Helicobacter
      pylori induces upregulation of the early growth response gene Egr-1 in gastric
      epithelial cells.
AB  - BACKGROUND AND AIMS: Helicobacter pylori, in particular cytotoxin associated gene
      (cag)+ strains, have been shown to enhance gastric epithelial cell proliferation
      in vivo, an effect that likely contributes to gastric carcinogenesis. Early
      growth response gene 1 (Egr-1) is a crucial regulator of cell growth,
      differentiation, and survival, which is known to play a role in carcinogenesis
      and cancer progression. The aims of this study were to: (1) examine whether H
      pylori could upregulate Egr-1 in gastric epithelial cell lines; (2) determine
      whether there was a differential response to infection with different strains;
      (3) examine the role of the cag pathogenicity island in this process; and (4)
      elucidate the molecular mechanisms leading to Egr-1 upregulation. METHODS AND
      RESULTS: We found that infection of AGS cells with cag+H pylori resulted in a
      rapid (1-2 hours) but transient increase in Egr-1 mRNA and protein levels whereas
      coculture with cag- isolates did not elicit this response. Furthermore, two
      independent cagE- isogenic mutants of H pylori also demonstrated impaired ability
      to upregulate Egr-1. Upregulation of Egr-1 protein was inhibited by the
      extracellular regulated kinase (ERK)1/2 inhibitor PD98059 and overexpression of
      dominant negative MEK1 downregulated Egr-1 luciferase reporter gene activity.
      Treatment of AGS cells with the epidermal growth factor receptor (EGFR) kinase
      inhibitors PD153035 and AG1478 resulted in a reduction in H pylori mediated Egr-1
      upregulation, demonstrating that EGFR transactivation plays a role in this early
      cellular process. CONCLUSIONS: Our findings show that cag+H pylori cause rapid
      induction of Egr-1 in gastric epithelial cells which may contribute to H pylori
      mediated pathogenesis.

PMID- 15863472
TI  - Anti-Saccharomyces cerevisiae antibodies in twins with inflammatory bowel
      disease.
AB  - BACKGROUND AND AIMS: An increased occurrence of anti-Saccharomyces cerevisiae
      antibodies (ASCA) is reported in unaffected members of families with Crohn's
      disease. Whether ASCA is a familial trait due to genetic factors or is caused by
      exposure to environmental factors is unknown. To assess the genetic influence of
      ASCA we studied its occurrence in a twin population. PATIENTS AND METHODS: ASCA
      were analysed in 98 twin pairs with inflammatory bowel disease and were related
      to clinical phenotype and CARD15/NOD2 genotype. RESULTS: ASCA were more common in
      Crohn's disease than in ulcerative colitis (40/70 (57%) twins v 5/43 (12%)
      twins). Associations with ileal Crohn's disease, stricturing/penetrating
      behaviour, and young age, but not CARD15/NOD2 were confirmed. ASCA were found in
      1/20 (5%) healthy siblings in discordant monozygotic pairs with Crohn's disease
      compared with 7/27 (26%) in discordant dizygotic pairs. Using the intraclass
      correlation coefficient (ICC), no agreement in ASCA titres was observed in
      discordant twin pairs with Crohn's disease, in monozygotic (ICC = -0.02) or
      dizygotic (ICC = -0.26) pairs. In contrast, strong agreement was seen within
      concordant monozygotic twin pairs with Crohn's disease (ICC = 0.76). CONCLUSIONS:
      These findings question the concept of ASCA as a marker of genetic susceptibility
      for Crohn's disease. The agreement in ASCA titres within concordant monozygotic
      twin pairs with Crohn's disease, suggests that the level of increase is
      genetically determined. We propose that ASCA are a marker of a response to an
      environmental antigen and that a specific gene(s) other than CARD15/NOD2
      determines the level of response and perhaps also specific phenotypic
      characteristics.

PMID- 15863473
TI  - Magnetic pulse affects a putative magnetoreceptor mechanism.
AB  - Clusters of superparamagnetic (SP) magnetite crystals have recently been
      identified in free nerve endings in the upper-beak skin of homing pigeons and are
      interpreted as being part of a putative magnetoreceptor system. Motivated by
      these findings, we developed a physical model that accurately predicts the
      dynamics of interacting SP clusters in a magnetic field. The main predictions
      are: 1), under a magnetic field, a group of SP clusters self-assembles into a
      chain-like structure that behaves like a compass needle under slowly rotating
      fields; 2), in a frequently changing field as encountered by a moving bird, a
      stacked chain is a structurally more stable configuration than a single chain;
      3), chain-like structures of SP clusters disrupt under strong fields applied at
      oblique angles; and 4), reassemble on a timescale of hours to days (assuming a
      viscosity of the cell plasma eta approximately 1 P). Our results offer a novel
      mechanism for magnetic field perception and are in agreement with the response of
      birds observed after magnetic-pulse treatments, which have been conducted in the
      past to specifically test if ferrimagnetic material is involved in
      magnetoreception, but which have defied explanation so far. Our theoretical
      results are supported by experiments on a technical SP model system using a high
      speed camera. We also offer new predictions that can be tested experimentally.

PMID- 15863474
TI  - Sedimentation velocity analysis of heterogeneous protein-protein interactions:
      sedimentation coefficient distributions c(s) and asymptotic boundary profiles
      from Gilbert-Jenkins theory.
AB  - Interacting proteins in rapid association equilibrium exhibit coupled migration
      under the influence of an external force. In sedimentation, two-component systems
      can exhibit bimodal boundaries, consisting of the undisturbed sedimentation of a
      fraction of the population of one component, and the coupled sedimentation of a
      mixture of both free and complex species in the reaction boundary. For the
      theoretical limit of diffusion-free sedimentation after infinite time, the shapes
      of the reaction boundaries and the sedimentation velocity gradients have been
      predicted by Gilbert and Jenkins. We compare these asymptotic gradients with
      sedimentation coefficient distributions, c(s), extracted from experimental
      sedimentation profiles by direct modeling with superpositions of Lamm equation
      solutions. The overall shapes are qualitatively consistent and the amplitudes and
      weight-average s-values of the different boundary components are quantitatively
      in good agreement. We propose that the concentration dependence of the area and
      weight-average s-value of the c(s) peaks can be modeled by isotherms based on
      Gilbert-Jenkins theory, providing a robust approach to exploit the bimodal
      structure of the reaction boundary for the analysis of experimental data. This
      can significantly improve the estimates for the determination of binding
      constants and hydrodynamic parameters of the complexes.

PMID- 15863475
TI  - Sedimentation velocity analysis of heterogeneous protein-protein interactions:
      Lamm equation modeling and sedimentation coefficient distributions c(s).
AB  - We describe algorithms for solving the Lamm equations for the reaction-diffusion
      sedimentation process in analytical ultracentrifugation, and examine the
      potential and limitations for fitting experimental data. The theoretical limiting
      case of a small, uniformly distributed ligand rapidly reacting with a larger
      protein in a "constant bath" of the ligand is recapitulated, which predicts the
      reaction boundary to sediment with a single sedimentation and diffusion
      coefficient. As a consequence, it is possible to express the sedimentation
      profiles of reacting systems as c(s) distribution of noninteracting Lamm equation
      solutions, deconvoluting the effects of diffusion. For rapid reactions, the
      results are quantitatively consistent with the "constant bath" approximation,
      showing c(s) peaks at concentration-dependent positions. For slower reactions,
      the deconvolution of diffusion is still partially successful, with c(s) resolving
      peaks that reflect the populations of sedimenting species. The transition between
      c(s) peaks describing reaction boundaries of moderately strong interactions (K(D)
      approximately 10(-6) M) or resolving sedimenting species was found to occur in a
      narrow range of dissociation rate constant between 10(-3) and 10(-4) s(-1). The
      integration of the c(s) peaks can lead to isotherms of species populations or s
      value of the reaction boundary, respectively, which can be used for the
      determination of the equilibrium binding constant.

PMID- 15863476
TI  - The fast gating mechanism in ClC-0 channels.
AB  - We investigate and then modify the hypothesis that a glutamate side chain acts as
      the fast gate in ClC-0 channels. We first create a putative open-state
      configuration of the prokaryotic ClC Cl- channel using its crystallographic
      structure as a basis. Then, retaining the same pore shape, the prokaryotic ClC
      channel is converted to ClC-0 by replacing all the nonconserved polar and charged
      residues. Using this open-state channel model, we carry out molecular dynamics
      simulations to study how the glutamate side chain can move between open and
      closed configurations. When the side chain extends toward the extracellular end
      of the channel, it presents an electrostatic barrier to Cl- conduction. However,
      external Cl- ions can push the side chain into a more central position where,
      pressed against the channel wall, it does not impede the motion of Cl- ions.
      Additionally, a proton from a low-pH external solution can neutralize the
      extended glutamate side chain, which also removes the barrier to conduction.
      Finally, we use Brownian dynamics simulations to demonstrate the influence of
      membrane potential and external Cl- concentration on channel open probability.

PMID- 15863477
TI  - Trapping, deformation, and rotation of giant unilamellar vesicles in octode
      dielectrophoretic field cages.
AB  - The behavior of freestanding lipid bilayer membranes under the influence of
      dielectric force potentials was studied by trapping, holding, and rotating
      individual giant unilamellar vesicles (GUVs) inside dielectrophoretic microfield
      cages. Using laser scanning confocal microscopy and three-dimensional image
      reconstructions of GUVs labeled with fluorescent membrane probes, field strength
      and frequency-dependent vesicle deformations were observed which are explained by
      calculations of the dielectric force potentials inside the cage. Dynamical
      membrane properties under the influence of the field cage were studied by
      fluorescence correlation spectroscopy, circumventing potential artifacts
      associated with measurements involving GUV immobilization on support surfaces.
      Lipid transport could be accelerated markedly by the applied fields, aided by
      hydrodynamic fluid streaming which was also studied by fluorescence correlation
      spectroscopy.

PMID- 15863478
TI  - Lateral diffusion coefficients of separate lipid species in a ternary raft
      forming bilayer: a Pfg-NMR multinuclear study.
AB  - By isotopical labeling lipid lateral diffusion coefficients for each of the
      membrane constituents, including cholesterol, have been measured by 1H, 2H, and
      19F pulsed field gradient NMR spectroscopy in macroscopically oriented lipid
      bilayers. This provides a means of obtaining detailed dynamic and compositional
      information in raft-forming lipid bilayers without introducing foreign molecules
      into the systems. The raft systems studied contained
      dioleoylphosphatidylcholine/dipalmitoylphosphatidylcholine (DPPC)/cholesterol at
      the molar ratios of 42.5:42.5:15 and 35:35:30 in excess water. At temperatures
      below 30 degrees C the raft system forms large (>1 microm) domains of a liquid
      ordered (l(o)) phase, in which the lipid lateral diffusion was approximately 5
      times slower than for the lipids in the surrounding liquid disordered (l(d))
      phase. Within each domain all lipid species showed the same diffusion
      coefficient, despite the very different structures of cholesterol and
      phospholipids. DPPC partitions exclusively into the l(o) domains, whereas
      cholesterol and dioleoylphosphatidylcholine were distributed in both l(o) and
      l(d) phases. The cholesterol concentration was found to be 10-20 mol % in the
      l(d) domain and 30-40 mol % in the l(o) domain. Comparison of these results with
      data from sphingomyelin-containing systems suggests that DPPC interacts more
      weakly with cholesterol than does sphingomyelin.

PMID- 15863479
TI  - Mechanically unfolding the small, topologically simple protein L.
AB  - beta-sheet proteins are generally more able to resist mechanical deformation than
      alpha-helical proteins. Experiments measuring the mechanical resistance of beta
      sheet proteins extended by their termini led to the hypothesis that parallel,
      directly hydrogen-bonded terminal beta-strands provide the greatest mechanical
      strength. Here we test this hypothesis by measuring the mechanical properties of
      protein L, a domain with a topology predicted to be mechanically strong, but with
      no known mechanical function. A pentamer of this small, topologically simple
      protein is resistant to mechanical deformation over a wide range of extension
      rates. Molecular dynamics simulations show the energy landscape for protein L is
      highly restricted for mechanical unfolding and that this protein unfolds by the
      shearing apart of two structural units in a mechanism similar to that proposed
      for ubiquitin, which belongs to the same structural class as protein L, but
      unfolds at a significantly higher force. These data suggest that the mechanism of
      mechanical unfolding is conserved in proteins within the same fold family and
      demonstrate that although the topology and presence of a hydrogen-bonded clamp
      are of central importance in determining mechanical strength, hydrophobic
      interactions also play an important role in modulating the mechanical resistance
      of these similar proteins.

PMID- 15863480
TI  - Constant pH molecular dynamics with proton tautomerism.
AB  - The current article describes a new two-dimensional lambda-dynamics method to
      include proton tautomerism in continuous constant pH molecular dynamics (CPHMD)
      simulations. The two-dimensional lambda-dynamics framework is used to devise a
      tautomeric state titration model for the CPHMD simulations involving carboxyl and
      histidine residues. Combined with the GBSW implicit solvent model, the new method
      is tested on titration simulations of blocked histidine and aspartic acid as well
      as two benchmark proteins, turkey ovomucoid third domain (OMTKY3) and
      ribonuclease A (RNase A). A detailed analysis of the errors inherent to the CPHMD
      methodology as well as those due to the underlying solvation model is given. The
      average absolute error for the computed pKa values in OMTKY3 is 1.0 pK unit. In
      RNase A the average absolute errors for the carboxyl and histidine residues are
      1.6 and 0.6 pK units, respectively. In contrast to the previous work, the new
      model predicts the correct sign for all the pKa shifts, but one, in the benchmark
      proteins. The predictions of the tautomeric states of His12 and His48 and the
      conformational states of His48 and His119 are in agreement with experiment. Based
      on the simulations of OMTKY3 and RNase A, the current work has demonstrated the
      capability of the CPHMD technique in revealing pH-coupled conformational dynamics
      of protein side chains.

PMID- 15863481
TI  - Interhead distance measurements in myosin VI via SHRImP support a simplified hand
      over-hand model.
AB  - Myosin VI walks in a hand-over-hand fashion with an average step size of 30 nm,
      which is much larger than its 10 nm lever arm. Recent experiments suggest that
      the myosin VI structure has an unfolded and flexible region in the proximal tail
      which makes such a large step possible. In addition, cryoelectron microscopy
      images of actomyosin VI show the two heads bound to the actin monomers with a
      broad distribution of distances, including some as close as a few nanometers.
      This observation, when combined with the existence of a flexible region in the
      structure, which takes part in stepping, challenged the hand-over-hand model. In
      the hand-over-hand model, the lever arm is considered to be rigid and the
      interhead separation should not be very different from 30 nm. We considered an
      alternative model in which myosin VI heads sequentially take 60 nm steps whereas
      the interhead separation alternates between a large and small value (x and 60 -
      x, where x < 30). To clarify these issues, we used a new technique, SHRImP, to
      measure the interhead distance of nearly rigor myosin VI molecules. Our data show
      a single peak at 29.3 +/- 0.7 nm, in agreement with the straightforward hand-over
      hand model.

PMID- 15863482
TI  - Cyanine dyes as intercalating agents: kinetic and thermodynamic studies on the
      DNA/Cyan40 and DNA/CCyan2 systems.
AB  - The interaction of cyanines with nucleic acids is accompanied by intense changes
      of their optical properties. Consequently these molecules find numerous
      applications in biology and medicine. Since no detailed information on the
      binding mechanism of DNA/cyanine systems is available, a T-jump investigation of
      the kinetics and equilibria of binding of the cyanines Cyan40 [3-methyl-2-(1,2,6
      trimethyl-4(1H)pyridinylidenmethyl)-benzothiazolium ion] and CCyan2 [3-methyl-2
      [2-methyl-3-(3-methyl-2(3H)-benzothiazolylidene)-1-propenyl]-benzothiazolium ion]
      with CT-DNA is performed at 25 degrees C, pH 7 and various ionic strengths.
      Bathochromic shifts of the dye absorption band upon DNA addition, polymer melting
      point displacement (DeltaT = 8-10 degrees C), site size determination (n = 2),
      and stepwise kinetics concur in suggesting that the investigated cyanines bind to
      CT-DNA primary by intercalation. Measurements with poly(dA-dT).poly(dA-dT) and
      poly(dG-dC).poly(dG-dC) reveal fair selectivity of CCyan2 toward G-C basepairs. T
      jump experiments show two kinetic effects for both systems. The binding process
      is discussed in terms of the sequence D + S left arrow over right arrow D,S left
      arrow over right arrow DS(I) left arrow over right arrow DS(II), which leads
      first to fast formation of an external complex D,S and then to a partially
      intercalated complex DS(I) which, in turn, converts to DS(II), a more stable
      intercalate. Absorption spectra reveal that both dyes tend to self-aggregate; the
      kinetics of CCyan2 self-aggregation is studied by T-jump relaxation and the
      results are interpreted in terms of dimer formation.

PMID- 15863483
TI  - Probing the role of negatively charged amino acid residues in ion permeation of
      skeletal muscle ryanodine receptor.
AB  - Sequence comparison suggests that the ryanodine receptors (RyRs) have pore
      architecture similar to that of the bacterial K+ channel KcsA. The lumenal loop
      linking the two most C-terminal transmembrane spanning segments in the RyRs has a
      predicted pore helix and an amino acid motif (GGGIG) similar to the selectivity
      filter (TVGYG) of KcsA identified by x-ray analysis. The RyRs have many
      negatively charged amino acid residues in the two regions linking the GGGIG motif
      and predicted pore helix with the two most C-terminal transmembrane spanning
      segments. We tested the role of these residues by generating single-site mutants,
      focusing on amino acid residues conserved among the mammalian RyRs. Replacement
      of two acidic residues immediately after the GGGIG motif in skeletal muscle
      ryanodine receptor (RyR1-D4899 and -E4900) with asparagine and glutamine
      profoundly affected ion permeation and selectivity. By comparison, mutagenesis of
      aspartate and glutamate residues in the putative linker regions showed a K+
      conductance and selectivity for Ca2+ compared to K+ (P(Ca)/P(K)) close to wild
      type. The results show that the negatively charged carboxyl oxygens of D4899 and
      E4900 side chains are major determinants of RyR ion conductance and selectivity.

PMID- 15863484
TI  - Topoisomerase IV bends and overtwists DNA upon binding.
AB  - Escherichia coli topoisomerase IV (Topo IV) is an essential ATP-dependent enzyme
      that unlinks sister chromosomes during replication and efficiently removes
      positive but not negative supercoils. In this article, we investigate the binding
      properties of Topo IV onto DNA in the absence of ATP using a single molecule
      micromanipulation setup. We find that the enzyme binds cooperatively (Hill
      coefficient alpha approximately 4) with supercoiled DNA, suggesting that the Topo
      IV subunits assemble upon binding onto DNA. It interacts preferentially with (+)
      rather than (-) supercoiled DNA (Kd+=0.15 nM, Kd-=0.23 nM) and more than two
      orders-of-magnitude more weakly with relaxed DNA (Kd0 approximately 36 nM). Like
      gyrase but unlike the eukaryotic Topo II, Topo IV bends DNA with a radius 0= 6.4
      nm and locally changes its twist and/or its writhe by 0.16 turn per bound
      complex. We estimate its free energy of binding and study the dynamics of
      interaction of Topo IV with DNA at the binding threshold. We find that the
      protein/DNA complex alternates between two states: a weakly bound state where it
      stays with probability p = 0.89 and a strongly bound state (with probability p =
      0.11). The methodology introduced here to characterize the Topo IV/DNA complex is
      very general and could be used to study other DNA/protein complexes.

PMID- 15863485
TI  - Strong repulsive forces between protein and oligo (ethylene glycol) self
      assembled monolayers: a molecular simulation study.
AB  - Restrained molecular dynamics simulations were performed to study the interaction
      forces of a protein with the self-assembled monolayers (SAMs) of S(CH2)4(EG)4OH,
      S(CH2)11OH, and S(CH2)11CH3 in the presence of water molecules. The force
      distance curves were calculated by fixing the center of mass of the protein at
      several separation distances from the SAM surface. Simulation results show that
      the relative strength of repulsive force acting on the protein is in the
      decreasing order of OEG-SAMs > OH-SAMs > CH3-SAMs. The force contributions from
      SAMs and water molecules, the structural and dynamic behavior of hydration water,
      and the flexibility and conformation state of SAMs were also examined to study
      how water structure at the interface and SAM flexibility affect the forces
      exerted on the protein. Results show that a tightly bound water layer adjacent to
      the OEG-SAMs is mainly responsible for the large repulsive hydration force.

PMID- 15863486
TI  - Chevron behavior and isostable enthalpic barriers in protein folding: successes
      and limitations of simple Go-like modeling.
AB  - It has been demonstrated that a "near-Levinthal" cooperative mechanism, whereby
      the common Go interaction scheme is augmented by an extra favorability for the
      native state as a whole, can lead to apparent two-state folding/unfolding
      kinetics over a broad range of native stabilities in lattice models of proteins.
      Here such a mechanism is shown to be generalizable to a simplified continuum (off
      lattice) Langevin dynamics model with a Calpha protein chain representation, with
      the resulting chevron plots exhibiting an extended quasilinear regime reminiscent
      of that of apparent two-state real proteins. Similarly high degrees of
      cooperativity are possible in Go-like continuum models with rudimentary pairwise
      desolvation barriers as well. In these models, cooperativity increases with
      increasing desolvation barrier height, suggesting strongly that two-state-like
      folding/unfolding kinetics would be achievable when the pairwise desolvation
      barrier becomes sufficiently high. Besides cooperativity, another generic folding
      property of interest that has emerged from published experiments on several
      apparent two-state proteins is that their folding relaxation under constant
      native stability (isostability) conditions is essentially Arrhenius, entailing
      high intrinsic enthalpic folding barriers of approximately 17-30 kcal/mol. Based
      on a new analysis of published data on barnase, here we propose that a similar
      property should also apply to a certain class of non-two-state proteins that fold
      with chevron rollovers. However, several continuum Go-like constructs considered
      here fail to predict any significant intrinsic enthalpic folding barrier under
      isostability conditions; thus the physical origin of such barriers in real
      proteins remains to be elucidated.

PMID- 15863487
TI  - The interplay between viscoelastic and thermodynamic properties determines the
      birefringence of F-actin gels.
AB  - F-actin gels of increasing concentrations (25-300 microM) display in vitro a
      progressive onset of birefringence due to orientational ordering of actin
      filaments. At F-actin concentrations <100 microM, this birefringence can be
      erased and restored at will by sonication and gentle flow, respectively. Hence,
      the orientational ordering does not result from a thermodynamic transition to a
      nematic phase but instead is due to mechanical stresses stored in the gels. In
      contrast, at F-actin concentrations > or =100 microM, gels display spontaneous
      birefringence recovery, at rest, which is the sign of true nematic ordering, in
      good agreement with statistical physics models of the isotropic/nematic
      transition. Well-aligned samples of F-actin gels could be produced and their
      small-angle x-ray scattering patterns are quite anisotropic. These patterns show
      no sign of filament positional short-range order and could be modeled by
      averaging the form factor with the Maier-Saupe nematic distribution function. The
      derived nematic order parameter S of the gels ranged from S = 0.7 at 300 microM
      to S = 0.4 at 25 microM. Both birefringence and small-angle x-ray scattering data
      indicate that, even in absence of cross-linking proteins, spontaneous cooperative
      alignment of actin filaments may arise in motile regions of living cells where F
      actin concentrations can reach values of a few 100 microM.

PMID- 15863488
TI  - Early postnatal changes in the perfusion index in term newborns with subclinical
      chorioamnionitis.
AB  - BACKGROUND: Chorioamnionitis (HCA) in term newborns is often subclinical and
      associated with neonatal morbidity and mortality. OBJECTIVE: To assess the value
      of the pulse oximetry perfusion index (PI) in the early prediction of subclinical
      HCA in term newborns. METHODS: PI cut-off values were first identified in 51 term
      newborns with HCA and 115 matched controls, retrospectively categorised on the
      basis of placental histology (study phase 1). The PI thresholds obtained were
      subsequently tested on an unselected case series of 329 prospectively recruited,
      term newborns (study phase 2). PI was evaluated during the first five minutes
      after delivery. Initial illness severity and short term clinical outcomes were
      determined. RESULTS: In study phase 1, newborns with HCA had lower PI one and
      five minutes (p<0.0001) after delivery, lower one minute Apgar score (p = 0.017),
      lower cord blood base excess (p = 0.0001), together with higher rates of
      admission to neonatal intensive care unit (p = 0.0001) and endotracheal
      intubation (p = 0.017), and higher SNAP-PE (p<0.0001) and NTISS (p<0.0001) scores
      than those without HCA. In the prospective validation phase of the study, the PI
      cut-off values generated (one minute < or =1.74, five minutes < or =2.18) showed
      100% sensitivity, 99.4% specificity, 93.7% positive predictive value, and 100%
      negative predictive value in identifying subclinical HCA. Early identification of
      HCA was associated with a decreased rate of admission to intensive care (p =
      0.012), as well as lower initial illness severity (p< or =0.0001) and therapeutic
      intensity (p = 0.0006) than the newborns with HCA in phase 1. CONCLUSION: These
      findings suggest that early PI monitoring is helpful in identifying HCA in term
      newborns.

PMID- 15863489
TI  - Monitoring of end tidal carbon dioxide and transcutaneous carbon dioxide during
      neonatal transport.
AB  - OBJECTIVE: To assess the accuracy of measurements of end tidal carbon dioxide
      (CO2) during neonatal transport compared with arterial and transcutaneous
      measurements. DESIGN: Paired end tidal and transcutaneous CO2 recordings were
      taken frequently during road transport of 21 ventilated neonates. The first
      paired CO2 values were compared with an arterial blood gas. The differences
      between arterial CO2 (Paco2), transcutaneous CO2 (TcPco2), and end tidal CO2
      (Petco2) were analysed. The Bland-Altman method was used to assess bias and
      repeatability. RESULTS: Petco2 correlated strongly with Paco2 and TcPco2.
      However, Petco2 underestimated Paco2 at a clinically unacceptable level (mean
      (SD) 1.1 (0.70) kPa) and did not trend reliably over time within individual
      subjects. The Petco2 bias was independent of Paco2 and severity of lung disease.
      CONCLUSIONS: Petco2 had an unacceptable under-recording bias. TcPco2 should
      currently be considered the preferred method of non-invasive CO2 monitoring for
      neonatal transport.

PMID- 15863490
TI  - Does sustained lung inflation at resuscitation reduce lung injury in the preterm
      infant?
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common outcome of preterm
      birth. Experimental animal work has shown that initial ventilation strategies
      injure the immature lung and may lead to BPD. Studies with asphyxiated babies
      have shown that, if tidal ventilation at birth is preceded by sustained lung
      inflation, larger inflation volumes can be achieved, which is thought to lead to
      clearance of lung fluid and formation of the functional residual capacity (FRC).
      OBJECTIVE: To see if sustained lung inflation at initial resuscitation of preterm
      babies would facilitate the removal of lung fluid, establish the FRC, and allow
      an even distribution of alveolar opening, permitting less aggressive ventilation,
      leading to a reduction in pulmonary inflammation and subsequent BPD. METHOD: The
      outcomes of 52 babies of less than 31 weeks gestation, resuscitated at birth
      using either a sustained lung inflation of five seconds or a conventional lung
      inflation of two seconds for the first assisted breath of resuscitation, were
      examined. Evidence of pulmonary inflammation was determined by quantification of
      interleukins 6, 10, and 1beta and tumour necrosis factor alpha in bronchoalveolar
      lavage fluid by enzyme linked immunosorbent assay. RESULTS: There were no
      significant differences in any of the cytokines. Death occurred in 3/26 babies in
      the conventional group and 6/26 babies in the sustained lung inflation group.
      Survival without BPD occurred in 13/26 and 14/26 respectively. CONCLUSION: The
      use of sustained lung inflation at resuscitation did not reduce lung injury, as
      measured by inflammatory markers.

PMID- 15863491
TI  - Does the use of 50% oxygen at birth in preterm infants reduce lung injury?
AB  - BACKGROUND: Bronchopulmonary dysplasia is an inflammatory fibrotic condition
      produced as a consequence of injurious influences in the neonatal lung. Exposing
      the premature lung to high concentrations of oxygen is thought to play an
      important part in lung injury pathogenesis. OBJECTIVE: To see if the amount of
      oxygen used during resuscitation at birth triggers events that lead to the
      subsequent lung injury and if a reduction in oxygen used leads to a reduction in
      lung injury. METHOD: The outcomes of newborn babies less than 31 weeks gestation
      who were resuscitated using either 50% or 100% oxygen were examined. Eight of the
      babies receiving 50% oxygen required an increase in their oxygen concentration.
      Evidence of pulmonary inflammation was determined by quantifying interleukin 6,
      1beta, and 10 and tumour necrosis factor alpha in bronchoalveolar lavage fluid by
      enzyme linked immunosorbent assay. RESULTS: There were no significant differences
      in any of the cytokines studied in either of the groups. Death occurred in 5/26
      (19%) babies who received 100% oxygen and 4/26 (15%) babies who received 50%
      oxygen. Survival without bronchopulmonary dysplasia at 36 weeks postmenstrual age
      occurred in 14/26 (54%) and 13/26 (50%). CONCLUSION: Reducing the oxygen to 50%
      at resuscitation did not influence either short or long term outcomes, but a
      small benefit could not be excluded. There was no increase in adverse clinical
      outcomes in babies who received 100% oxygen.

PMID- 15863492
TI  - Selective and ATP-dependent translocation of peptides by the homodimeric ATP
      binding cassette transporter TAP-like (ABCB9).
AB  - The transporter associated with antigen processing (TAP)-like (TAPL, ABCB9)
      belongs to the ATP-binding cassette transporter family, which translocates a vast
      variety of solutes across membranes. The function of this half-size transporter
      has not yet been determined. Here, we show that TAPL forms a homodimeric complex,
      which translocates peptides across the membrane. Peptide transport strictly
      requires ATP hydrolysis. The transport follows Michaelis-Menten kinetics with low
      affinity and high capacity. Different nucleotides bind and energize the transport
      with a slight predilection for purine bases. The peptide specificity is very
      broad, ranging from 6-mer up to at least 59-mer peptides with a preference for 23
      mers. Peptides are recognized via their backbone, including the free N and C
      termini as well as side chain interactions. Although related to TAP, TAPL is
      unique as far as its interaction partners, transport properties, and substrate
      specificities are concerned, thus excluding that TAPL is part of the peptide
      loading complex in the classic route of antigen processing via major
      histocompatibility complex class I molecules.

PMID- 15863493
TI  - Distinct transcriptional control mechanisms of killer immunoglobulin-like
      receptors in natural killer (NK) and in T cells.
AB  - Killer immunoglobulin-like receptors (KIR) are expressed by natural killer (NK)
      cells and by subsets of CD4+ and CD8+ T cells, which are therefore thought to be
      subject to similar regulatory mechanisms. Here, we show that the transcriptional
      machinery to express KIR is limited to NK and T cells; however, the KIR
      transcriptional control differs between these two types of lymphocytes. T cells
      selectively express transcriptional activators binding to positions -52 to -61 of
      the KIR promoter, whereas an AML site around position-98 is relevant for
      transcription in NK cells. Although KIR expression is restricted to subsets of
      memory T cells, our studies demonstrate that transcriptional activators for KIRs
      are not acquired during T cell differentiation but are already present in naive T
      cells, suggesting a basic role of KIRs in T cell biology. We suggest that the
      regulated expression of KIRs in T cells profoundly influences peripheral
      tolerance and antigen-specific immune responses.

PMID- 15863494
TI  - ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A
      serine phosphorylation events.
AB  - The epidermal growth factor receptor family member ERBB4 is required for mammary
      gland development and lactation. ERBB4 activities in the breast are mediated
      through the signal transducer and activator of transcription (STAT) family member
      STAT5A, and ERBB4 directly activates STAT5A, in part, through phosphorylation of
      STAT5A at the regulatory Tyr-694. Here we show that STAT5A regulation by ERBB4 is
      also mediated through STAT5A serine phosphorylation. Using a reverse-phase high
      performance liquid chromatography tandem mass spectrometry analysis of
      proteolytically digested STAT5A coexpressed with ERBB4, we identified STAT5A
      serine phosphorylations at the previously described Ser-779 and at the novel Ser
      127/Ser-128. Immunohistochemistry of wild-type and ERBB4-null mammary glands at
      late pregnancy showed that ERBB4 expression was required for STAT5A
      phosphorylation at Ser-779. Independent serine-to-alanine residue substitutions
      in full-length STAT5A revealed that although STAT5A Ser-779 phosphorylation was
      dispensable for phosphorylation of STAT5A at Tyr-694 and subsequent DNA binding,
      Ser-779 was required to stabilize an interaction with ERBB4 and mediate ERBB4
      induced STAT5A stimulation of gene expression. STAT5A Ser-127/Ser-128, on the
      other hand, was required for ERBB4-induced phosphorylation of Tyr-694, whereas
      Ser-779 and as yet unidentified tyrosine residues were phosphorylated in the
      absence of Ser-127/Ser-128. In addition, STAT5A S127A/S128A remained associated
      with ERBB4 but failed to bind DNA or activate transcription in response to ERBB4
      coexpression. Our studies demonstrate that phosphorylation of STAT5A at Ser
      127/Ser-128 and Ser-779 are obligatory events regulating ERBB4-mediated
      activation of STAT5A.

PMID- 15863495
TI  - Membrane-proximal {alpha}/{beta} stalk interactions differentially regulate
      integrin activation.
AB  - The affinity of integrin-ligand interaction is regulated extracellularly by
      divalent cations and intracellularly by inside-out signaling. We report here that
      the extracellular, membrane-proximal alpha/beta stalk interactions not only
      regulate cation-induced integrin activation but also play critical roles in
      propagating inside-out signaling. Two closely related integrins, alphaIIbbeta3
      and alphaVbeta3, share high structural homology and bind to similar ligands in an
      RGD-dependent manner. Despite these structural and functional similarities, they
      exhibit distinct responses to Mn(2+). Although alphaVbeta3 showed robust ligand
      binding in the presence of Mn(2+), alphaIIbbeta3 showed a limited increase but
      failed to achieve full activation. Swapping alpha stalk regions between alphaIIb
      and alphaV revealed that the alpha stalk, but not the ligand-binding head region,
      was responsible for the difference. A series of alphaIIb/alphaV domain-swapping
      chimeras were constructed to identify the responsible domain. Surprisingly, the
      minimum component required to render alphaIIbbeta3 susceptible to Mn(2+)
      activation was the alphaV calf-2 domain, which does not contain any divalent
      cation-binding sites. The calf-2 domain makes interface with beta epidermal
      growth factor 4 and beta tail domain in three-dimensional structure. The effect
      of calf-2 domain swapping was partially reproduced by mutating the specific amino
      acid residues in the calf-2/epidermal growth factor 4-beta tail domain interface.
      When this interface was constrained by an artificially introduced disulfide
      bridge, the Mn(2+)-induced alphaVbeta3-fibrinogen interaction was significantly
      impaired. Notably, a similar disulfide bridge completely abrogated fibrinogen
      binding to alphaIIbbeta3 when alphaIIbbeta3 was activated by cytoplasmic tail
      truncation to mimic inside-out signaling. Thus, disruption/formation of the
      membrane-proximal alpha/beta stalk interface may act as an on/off switch that
      triggers integrin-mediated bidirectional signaling.

PMID- 15863496
TI  - Mitochondrial respiratory chain and NAD(P)H oxidase are targets for the
      antiproliferative effect of carbon monoxide in human airway smooth muscle.
AB  - Carbon monoxide (CO), one of the end products of heme oxygenase activity,
      inhibits smooth muscle proliferation by decreasing ERK1/2 phosphorylation and
      cyclin D1 expression, a signaling pathway that is known to be modulated by
      reactive oxygen species (ROS) in airway smooth muscle cells (ASMCs). Two
      important sources of ROS involved in cell signaling are the membrane NAD(P)H
      oxidase and the mitochondrial respiratory chain. Thus, that CO could modulate
      redox signaling in ASMCs by interacting with the heme moiety of NAD(P)H oxidase
      and/or the respiratory chain is a plausible hypothesis. Here we show that a
      recently identified carbon monoxide-releasing molecule, [Ru(CO)3Cl2]2 (or CORM-2)
      1) inhibits NAD(P)H oxidase cytochrome b558 activity, 2) increases oxidant
      production by the mitochondria, and 3) inhibits ASMC proliferation and
      phosphorylation of the ERK1/2 mitogen-activated protein kinase and expression of
      cyclin D1, two critical pathways involved in muscle proliferation. No such
      effects were observed with the negative control (Ru(Me2SO)4Cl2), which does not
      contain CO groups. Because both diphenylene iodinium or apocynin (inhibitors of
      NAD(P)H oxidase) and rotenone (a molecule that increases mitochondrial ROS
      production by blocking the respiratory chain) mimicked the effect of CORM-2 on
      cyclin D1 expression and ASMC proliferation, the antiproliferative effect of CORM
      2 is probably related to inhibition of cytochromes on both NAD(P)H oxidase and
      the respiratory chain. The involvement of increased mitochondria-derived oxidants
      is substantiated by the findings showing that the antioxidant N-acetylcysteine
      partially inhibited the effects of CORM-2. This study provides a new mechanism to
      explain redox signaling by CO.

PMID- 15863497
TI  - Proteolytic cleavage of extracellular secreted {alpha}-synuclein via matrix
      metalloproteinases.
AB  - Although alpha-synuclein is the main structural component of the insoluble
      filaments that form Lewy bodies in Parkinson disease (PD), its physiological
      function and exact role in neuronal death remain poorly understood. In the
      present study, we examined the possible functional relationship between alpha
      synuclein and several forms of matrix metalloproteinases (MMPs) in the human
      dopaminergic neuroblastoma (SK-N-BE) cell line. When SK-N-BE cells were
      transiently transfected with alpha-synuclein, it was secreted into the
      extracellular culture media, concomitantly with a significant decrease in cell
      viability. Also the addition of nitric oxide-generating compounds to the cells
      caused the secreted alpha-synuclein to be digested, producing a small fragment
      whose size was similar to that of the fragment generated during the incubation of
      alpha-synuclein with various MMPs in vitro. Among several forms of MMPs, alpha
      synuclein was cleaved most efficiently by MMP-3, and MALDI-TOF mass spectra
      analysis showed that alpha-synuclein is cleaved from its C-terminal end with at
      least four cleavage sites within the non-Abeta component of AD amyloid sequence.
      Compared with the intact form, the protein aggregation of alpha-synuclein was
      remarkably facilitated in the presence of the proteolytic fragments, and the
      fragment-induced aggregates showed more toxic effect on cell viability. Moreover,
      the levels of MMP-3 were also found to be increased significantly in the rat PD
      brain model produced by the cerebral injection of 6-hydroxydopamine into the
      substantia nigra. The present study suggests that the extracellularly secreted
      alpha-synuclein could be processed via the activation of MMP-3 in a selective
      manner.

PMID- 15863498
TI  - Molecular basis of intramolecular electron transfer in sulfite-oxidizing enzymes
      is revealed by high resolution structure of a heterodimeric complex of the
      catalytic molybdopterin subunit and a c-type cytochrome subunit.
AB  - Sulfite-oxidizing molybdoenzymes convert the highly reactive and therefore toxic
      sulfite to sulfate and have been identified in insects, animals, plants, and
      bacteria. Although the well studied enzymes from higher animals serve to detoxify
      sulfite that arises from the catabolism of sulfur-containing amino acids, the
      bacterial enzymes have a central role in converting sulfite formed during
      dissimilatory oxidation of reduced sulfur compounds. Here we describe the
      structure of the Starkeya novella sulfite dehydrogenase, a heterodimeric complex
      of the catalytic molybdopterin subunit and a c-type cytochrome subunit, that
      reveals the molecular mechanism of intramolecular electron transfer in sulfite
      oxidizing enzymes. The close approach of the two redox centers in the protein
      complex (Mo-Fe distance 16.6 A) allows for rapid electron transfer via tunnelling
      or aided by the protein environment. The high resolution structure of the complex
      has allowed the identification of potential through-bond pathways for electron
      transfer including a direct link via Arg-55A and/or an aromatic-mediated pathway.
      A potential site of electron transfer to an external acceptor cytochrome c was
      also identified on the SorB subunit on the opposite side to the interaction with
      the catalytic SorA subunit.

PMID- 15863499
TI  - Asymmetric functioning of dimeric metabotropic glutamate receptors disclosed by
      positive allosteric modulators.
AB  - The recent discovery of positive allosteric modulators (PAMs) for G-protein
      coupled receptors open new possibilities to control a number of physiological and
      pathological processes. Understanding the mechanism of action of such compounds
      will provide new information on the activation process of these important
      receptors. Within the last 10 years, a number of studies indicate that G-protein
      coupled receptors can form dimers, but the functional significance of this
      phenomenon remains elusive. Here we used the metabotropic glutamate receptors as
      a model, because these receptors, for which PAMs have been identified, are
      constitutive dimers. We used the quality control system of the GABA(B) receptor
      to generate metabotropic glutamate receptor dimers in which a single subunit
      binds a PAM. We show that one PAM/dimer is sufficient to enhance receptor
      activity. Such a potentiation can still be observed if the subunit unable to bind
      the PAM is also made unable to activate G-proteins. However, the PAM acts as a
      non-competitive antagonist when it binds in the subunit that cannot activate G
      proteins. These data are consistent with a single heptahelical domain reaching
      the active state per dimer during receptor activation.

PMID- 15863500
TI  - Conformational dependence of intracellular NADH on metabolic state revealed by
      associated fluorescence anisotropy.
AB  - Global analysis of fluorescence and associated anisotropy decays of intrinsic
      tissue fluorescence offers a sensitive and non-invasive probe of the
      metabolically critical free/enzyme-bound states of intracellular NADH in neural
      tissue. Using this technique, we demonstrate that the response of NADH to the
      metabolic transition from normoxia to hypoxia is more complex than a simple
      increase in NADH concentration. The concentration of free NADH, and that of an
      enzyme bound form with a relatively low lifetime, increases preferentially over
      that of other enzyme bound NADH species. Concomitantly, the intracellular
      viscosity is reduced, likely due to the osmotic swelling of mitochondria. These
      conformation and environmental changes effectively decrease the tissue
      fluorescence average lifetime, causing the usual total fluorescence increase
      measurements to significantly underestimate the calculated concentration
      increase. This new discrimination of changes in NADH concentration, conformation,
      and environment provides the foundation for quantitative functional imaging of
      neural energy metabolism.

PMID- 15863501
TI  - Cellular distribution, post-translational modification, and tumorigenic potential
      of human group III secreted phospholipase A(2).
AB  - Human group III secreted phospholipase A(2) (sPLA(2)-III) consists of a central
      group III sPLA(2) domain flanked by unique N- and C-terminal domains. We found
      that the sPLA(2) domain alone was sufficient for its catalytic activity and for
      its prostaglandin E(2) (PGE(2))-generating functions in various cell types. In
      several if not all cell types, the N- and C-terminal domains of sPLA(2)-III were
      proteolytically removed, leading to the production of the form containing only
      the sPLA(2) domain, which could be further N-glycosylated at two consensus sites.
      Immunohistochemistry demonstrated that sPLA(2)-III was preferentially expressed
      in the microvascular endothelium in human tissues with inflammation, ischemic
      injury, and cancer. In support of this, sPLA(2)-III was induced in cultured
      microvascular endothelial cells after stimulation with proinflammatory cytokines.
      Expression of sPLA(2)-III was also associated with various tumor cells, and
      colorectal cancer cells transfected with sPLA(2)-III exhibited enhanced PGE(2)
      production and cell proliferation, which required sPLA(2)-III catalytic activity.
      When implanted into nude mice, the sPLA(2)-III-transfected cells formed larger
      solid tumors with increased angiogenesis compared with control cells. Moreover,
      small interfering RNA for sPLA(2)-III significantly reduced PGE(2) production and
      proliferation of colorectal cancer cells. Taken together, these results reveal
      unique cell type-specific processing and N-glycosylation of sPLA(2)-III and the
      potential role of this enzyme in cancer development by stimulating tumor cell
      growth and angiogenesis.

PMID- 15863502
TI  - An early event in adipogenesis, the nuclear selection of the CCAAT enhancer
      binding protein {beta} (C/EBP{beta}) mRNA by HuR and its translocation to the
      cytosol.
AB  - HuR is a ligand for nuclear mRNAs containing adenylate-uridylate-rich elements in
      the 3'-untranslated region. Once bound to the mRNA, HuR is recognized by adapter
      proteins that then facilitate nuclear export of the complex. In the cytosol, HuR
      is thought to function to control stability and translation of its ligand
      message. In the 3T3-L1 cells HuR is constitutively expressed and localized
      predominantly to the nucleus in the preadipocytes. However, within 30 min of
      exposure to the differentiation stimulus the HuR content in the cytosol
      increases, consistent with HuR regulating the availability of relevant mRNAs for
      translation. Using in vitro RNA gel shifts, we have demonstrated that the CCAAT
      enhancer-binding protein beta (C/EBPbeta) message is a ligand for HuR. Within 2 h
      of initiation of the differentiation process, HuR complexes containing C/EBPbeta
      mRNA could be isolated from the cytosolic compartment. Importantly, the process
      appears to be highly selective, as cyclin D1, which contains a putative HuR
      binding site and is expressed on the same time frame as C/EBPbeta, was not found
      in the immunoprecipitated messenger ribonucleoprotein complexes. The proximity of
      this event to adipogenic stimuli and the importance of C/EBPbeta to the
      differentiation process have led us to hypothesize a role for HuR in the
      regulation of the onset of adipogenesis. In support of this hypothesis, small
      interfering RNA suppression of HuR protein content resulted in an inhibition of
      C/EBPbeta protein expression and an attenuation of the differentiation process.

PMID- 15863503
TI  - Accumulation of diacylglycerol in the Chlamydia inclusion vacuole: possible role
      in the inhibition of host cell apoptosis.
AB  - Intracellular pathogens have developed strategies to survive for extended periods
      inside their host cells. These include avoidance of host microbicidal effectors,
      often by sequestration in a protected subcompartment of the host cell. In some
      cases, the parasites exert also an antiapoptotic effect that prolongs the life of
      the infected host cell. Chlamydia utilizes both strategies, but the underlying
      molecular mechanisms are incompletely understood. Comparatively, little is known
      regarding the effects that Chlamydia exerts on the metabolism and distribution of
      the host cell lipids. The expression of fluorescently tagged C1 domains revealed
      that diacylglycerol is greatly accumulated in the immediate vicinity of Chlamydia
      inclusion vacuoles. The concentrated diacylglycerol recruits protein kinase
      Cdelta (PKCdelta), a proapoptotic effector, to the immediate vicinity of the
      vacuole. PKCdelta normally exerts its pro-apoptotic effects at the mitochondria
      and in the nucleus. We speculate that Chlamydia antagonizes the pro-apoptotic
      effect of PKCdelta by sequestering the enzyme on the inclusion vacuole away from
      its conventional target sites. Accordingly, we found that the ectopic expression
      of a catalytic fragment of PKCdelta that cannot be recruited by the vacuole,
      because it lacks a functional C1 domain, overcame the anti-apoptotic effect of
      the bacteria. The scavenging of pro-apoptotic factors may provide a novel
      mechanism whereby pathogens promote their own survival by extending the life of
      the host cells they infect.

PMID- 15863504
TI  - Clotrimazole inhibits hemoperoxidase of Plasmodium falciparum and induces
      oxidative stress. Proposed antimalarial mechanism of clotrimazole.
AB  - The mechanism of antimalarial activity of clotrimazole was studied placing
      emphasis on its role in inhibiting hemoperoxidase for inducing oxidative stress
      in Plasmodium falciparum. Clotrimazole, in the presence of H2O2, causes
      irreversible inactivation of the enzyme, and the inactivation follows pseudo
      first order kinetics, consistent with a mechanism-based (suicide) mode. The
      pseudo-first order kinetic constants are ki = 2.85 microM, k(inact) = 0.9 min(
      1), and t(1/2) = 0.77 min. The one-electron oxidation product of clotrimazole has
      been identified by EPR spectroscopy as the 5,5'-dimethyl-1-pyrroline N-oxide
      (DMPO) adduct of the nitrogen-centered radical (aN = 15 G), and as DMPO protects
      against inactivation, this radical is involved in the inactivation process.
      Binding studies indicate that the clotrimazole oxidation product interacts at the
      heme moiety, and the heme-clotrimazole adduct has been dissociated from the
      inactivated enzyme and identified (m/z 1363) by mass analysis. We found that the
      inhibition of hemoperoxidase increases the accumulation of H2O2 in P. falciparum
      and causes oxidative stress. Furthermore, the inhibition of hemoperoxidase
      correlates well with the inhibition of parasite growth. The results described
      herein indicate that the antimalarial activity of clotrimazole might be due to
      the inhibition of hemoperoxidase and subsequent development of oxidative stress
      in P. falciparum.

PMID- 15863505
TI  - Differential roles for Sox15 and Sox2 in transcriptional control in mouse
      embryonic stem cells.
AB  - Sox family transcription factors play essential roles in cell differentiation,
      development, and sex determination. Sox2 was previously thought to be the sole
      Sox protein expressed in mouse embryonic stem (ES) cells. Sox2 associates with
      Oct3/4 to maintain self-renewal of ES cells. In the current study, digital
      differential display identified transcripts for an additional Sox family member,
      Sox15, enriched in mouse ES cells. Reverse transcription-PCR confirmed that Sox15
      expression is highest in undifferentiated ES cells and repressed upon
      differentiation. Sox15 is expressed at low levels in several tissues, including
      testis and muscle. In vitro studies showed that Sox15, like Sox2, associated with
      Oct3/4 on DNA sequences containing the octamer motif and Sox-binding site. Gel
      mobility shift assays and SELEX analyses showed that Sox15 binds similar DNA
      sequences as Sox2 but with weaker affinity. In contrast to the early embryonic
      lethality observed in Sox2-null mice, Sox15-null ES cells and mice were grossly
      normal. DNA microarray analyses revealed that Otx2, Ctgf, Ebaf, and Hrc are
      dysregulated in Sox15-null ES cells, however. Chromatin immunoprecipitation
      showed that Sox15, but not Sox2, bound to a Sox consensus binding site within the
      Hrc gene. Taken together, these data demonstrate differential roles for Sox15 and
      Sox2 in transcriptional control in mouse ES cells.

PMID- 15863506
TI  - Thrombopoietin complements G(i)- but not G(q)-dependent pathways for integrin
      {alpha}(IIb){beta}(3) activation and platelet aggregation.
AB  - Binding of thrombopoietin (TPO) to the cMpl receptor on human platelets
      potentiates aggregation induced by a number of agonists, including ADP. In this
      work, we found that TPO was able to restore ADP-induced platelet aggregation upon
      blockade of the G(q)-coupled P2Y1 purinergic receptor but not upon inhibition of
      the G(i)-coupled P2Y12 receptor. Moreover, TPO triggered platelet aggregation
      upon co-stimulation of G(z) by epinephrine but not upon co-stimulation of G(q) by
      the thromboxane analogue U46619. Platelet aggregation induced by TPO and G(i)
      stimulation was biphasic, and cyclooxygenase inhibitors prevented the second but
      not the first phase. In contrast to ADP, TPO was unable to induce integrin
      alpha(IIb)beta(3) activation, as evaluated by binding of both fibrinogen and PAC
      1 monoclonal antibody. However, ADP-induced activation of integrin
      alpha(IIb)beta(3) was blocked by antagonists of the G(q)-coupled P2Y1 receptor
      but was completely restored by the simultaneous co-stimulation of cMpl receptor
      by TPO. Inside-out activation of integrin alpha(IIb)beta(3) induced by TPO and
      G(i) stimulation occurred independently of thromboxane A(2) production and was
      not mediated by protein kinase C, MAP kinases, or Rho-dependent kinase.
      Importantly, TPO and G(i) activation of integrin alpha(IIb)beta(3) was suppressed
      by wortmannin and Ly294002, suggesting a critical regulation by
      phosphatidylinositol 3-kinase. We found that TPO did not activate phospholipase C
      in human platelets and was unable to restore ADP-induced phospholipase C
      activation upon blockade of the G(q)-coupled P2Y1 receptor. TPO induced a rapid
      and sustained activation of the small GTPase Rap1B through a pathway dependent on
      phosphatidylinositol 3-kinase. In ADP-stimulated platelets, Rap1B activation was
      reduced, although not abolished, upon blockade of the P2Y1 receptor. However,
      accumulation of GTP-bound Rap1B in platelets activated by co-stimulation of cMpl
      and P2Y12 receptor was identical to that induced by the simultaneous ligation of
      P2Y1 and P2Y12 receptor by ADP. These results indicate that TPO can integrate
      G(i), but not G(q), stimulation and can efficiently support integrin
      alpha(IIb)beta(3) activation platelet aggregation by an alternative signaling
      pathway independent of phospholipase C but involving the phosphatidylinositol 3
      kinase and the small GTPase Rap1B.

PMID- 15863507
TI  - Selective induction of the tumor marker glutathione S-transferase P1 by
      proteasome inhibitors.
AB  - Exposure of cells to a wide variety of chemoprotective compounds confers
      resistance to a broad set of carcinogens. For a subset of the chemoprotective
      compounds, protection is generated by an increase in the abundance of phase 2
      detoxification enzymes such as glutathione S-transferases (GSTs). Transcription
      factor Nrf2, which is sequestered in the cytoplasm by Keap1 (Kelch-like ECH
      associated protein-1) under unstimulated conditions, regulates the induction of
      phase 2 enzymes. In this study, to explore the role of the proteasome in the
      detoxification response, we tested the effect of proteasome inhibitors such as
      MG132, clasto-lactacystin beta-lactone, and lactacystin on the induction of GST
      isozymes and found that these inhibitors selectively induced the class Pi GST
      isozyme (GST P1). Down-regulation of the proteasome by antisense oligonucleotides
      or RNA interference indeed resulted in significant up-regulation of GST P1,
      suggesting that a decline in the proteasome activity could be directly or
      indirectly linked to the induction of GST P1. From the functional analysis of
      various deletion constructs of the upstream regulatory region of the GST P1
      promoter, GST P1 enhancer I was identified as the response element for proteasome
      inhibition. Overexpression of the wild-type and dominant-negative forms of Nrf2
      and Keap1 had little effect on the induction of GST P1 not only by the proteasome
      inhibitor, but also by phase 2-inducing isothiocyanate, suggesting that there may
      be a process of GST P1 induction distinct from other phase 2 gene induction
      mechanisms. Because GST P1 is highly and specifically induced during early
      hepatocarcinogenesis as well as in hepatocellular carcinoma cells, these data may
      provide a potential critical role for the proteasome in the induction of a
      cellular defense program associated with carcinogenesis.

PMID- 15863508
TI  - Role of the endoplasmic reticulum unfolded protein response in glomerular
      epithelial cell injury.
AB  - C5b-9-induced glomerular epithelial cell (GEC) injury in vivo (in passive Heymann
      nephritis) and in culture is associated with damage to the endoplasmic reticulum
      (ER) and increased expression of ER stress proteins. Induction of ER stress
      proteins is enhanced via cytosolic phospholipase A(2) (cPLA(2)) and limits
      complement-dependent cytotoxicity. The present study addresses another aspect of
      the ER unfolded protein response, i.e. activation of protein kinase R-like ER
      kinase (PERK or pancreatic ER kinase), which phosphorylates eukaryotic
      translation initiation factor 2-alpha (eIF2alpha), thereby generally suppressing
      translation and decreasing the protein load on a damaged ER. Phosphorylation of
      eIF2alpha was enhanced significantly in glomeruli of proteinuric rats with
      passive Heymann nephritis, compared with control. In cultured GECs, complement
      induced phosphorylation of eIF2alpha and reduced protein synthesis, and
      complement-stimulated phosphorylation of eIF2alpha was enhanced by overexpression
      of cPLA(2). Ischemia-reperfusion in vitro (deoxyglucose plus antimycin A followed
      by glucose re-exposure) also stimulated eIF2alpha phosphorylation and reduced
      protein synthesis. Complement and ischemia-reperfusion induced phosphorylation of
      PERK (which correlates with activation), and fibroblasts from PERK knock-out mice
      were more susceptible to complement- and ischemia-reperfusion-mediated
      cytotoxicity, as compared with wild type fibroblasts. The GEC protein, nephrin,
      plays a key role in maintaining glomerular permselectivity. In contrast to a
      general reduction in protein synthesis, translation regulated by the 5'-end of
      mouse nephrin mRNA during ER stress was paradoxically maintained, probably due to
      the presence of short open reading frames in this mRNA segment. Thus,
      phosphorylation of eIF2alpha and consequent general reduction in protein
      synthesis may be a novel mechanism for limiting complement- or ischemia
      reperfusion-dependent GEC injury.

PMID- 15863509
TI  - Identification and characterization of novel isoforms of human DP-1: DP-1{alpha}
      regulates the transcriptional activity of E2F1 as well as cell cycle progression
      in a dominant-negative manner.
AB  - The cell cycle-regulating transcription factors DP-1 and E2F form a heterodimeric
      complex and play a central role in cell cycle progression. Two different DP
      subunits (DP-1 and DP-2) exist in humans. In this study, we identified two novel
      DP-1 isoforms (DP-1alpha and DP-1beta) and characterized their structure and
      function. DP-1alpha is composed of 278 amino acids and lacks a portion of the C
      terminal heterodimerization domain, whereas DP-1beta is composed of 357 amino
      acids with a frameshift that causes truncation of the C-terminal domain. Yeast
      two-hybrid and immunoprecipitation assays demonstrated that DP-1alpha binding to
      E2F1 was significantly reduced as compared with that of wild-type DP-1 or DP
      1beta. Immunofluorescence analysis revealed that the subcellular localization of
      both DP-1 isoforms changed from the cytoplasm to the nucleus in HEK 293 cells
      cotransfected with E2F1 and wild-type DP-1 or DP-1beta. However, such a
      translocation for DP-1alpha was barely observed. Reverse transcription-PCR
      results showed that the three DP-1 isoforms are expressed ubiquitously at equal
      levels in several normal human tissues. We also demonstrated the expression of
      these isoforms at the protein level by Western blotting. Interestingly, we
      observed a significant decrease in transcriptional activity, a marked delay of
      cell cycle progression, and an inhibition of cell proliferation in DP-1alpha
      transfected HEK 293 cells. Together, the results of the present study suggest
      that DP-1alpha is a novel isoform of DP-1 that acts as a dominant-negative
      regulator of cell cycle progression.

PMID- 15863510
TI  - Ascochlorin inhibits matrix metalloproteinase-9 expression by suppressing
      activator protein-1-mediated gene expression through the ERK1/2 signaling
      pathway: inhibitory effects of ascochlorin on the invasion of renal carcinoma
      cells.
AB  - The expression of matrix metalloproteinases (MMPs) has been implicated in the
      invasion and metastasis of cancer cells. Here we examined the effect of
      ascochlorin, a prenyl-phenol anti-tumor compound from the fungus Ascochyta
      viciae, on the regulation of signaling pathways that control MMP-9 expression in
      human renal carcinoma (Caki-1) cells. Ascochlorin reduced the invasive activity
      of Caki-1 cells and inhibited phorbol 12-myristate 13-acetate-induced increases
      in MMP-9 expression and activity in a dose-dependent manner. Reporter gene,
      electrophoretic mobility shift, kinase inhibitor assays, and in vitro kinase
      assay showed that ascochlorin inhibits MMP-9 gene expression by suppressing
      activation of the nuclear transcription factor activator protein-1 (AP-1) via the
      extracellular signal-regulated kinase 1 and 2 pathway. The AP-1 family member
      most specifically affected by ascochlorin was Fra-1. Ascochlorin did not affect
      the activation of the c-Jun N-terminal or p38 kinase pathways. Moreover,
      transfection of Caki-1 cells with AP-1 decoy oligodeoxynucleotides resulted in
      the suppression of phorbol 12-myristate 13-acetate-induced MMP-9 expression and
      invasion. In conclusion, ascochlorin represents a unique natural anti-tumor
      compound that specifically inhibits MMP-9 activity through suppression of AP-1
      dependent induction of MMP-9 gene expression.

PMID- 15863512
TI  - Def1p is involved in telomere maintenance in budding yeast.
AB  - Saccharomyces Rrm3p, a member of Pif1 5'-3' DNA helicase subfamily, helps
      replication forks traverse protein-DNA complexes, including the telomere. Here we
      have identified an Rrm3p interaction protein known to be Def1p. In def1 mutants,
      telomeres were approximately 200-bp shorter than that in wild-type cells. DEF1 is
      also required for the stable maintenance of mitochondrial DNA, and the telomere
      shortening phenotype seen in def1 cells is not a secondary consequence of the
      mitochondrion defect. A combination of DEF1 null mutation with deletion of EST2
      or EST3 resulted in an accelerated senescence phenotype, suggesting that Def1p is
      not involved in the telomerase recruitment pathway. In the absence of telomerase,
      cells escape senescence by either amplifying Y' regions or TG-telomeric repeats
      to generate type I or type II survivors, respectively. Only type I survivors were
      recovered from both def1Delta est2Delta and def1Delta est3Delta double mutant
      cells, further suggesting that the function of Def1p in telomere maintenance is
      specific. Our novel findings of the functions of Def1p in telomere and
      mitochondria suggested that Def1p plays multiple roles in yeast.

PMID- 15863511
TI  - Domain 2 of the urokinase receptor contains an integrin-interacting epitope with
      intrinsic signaling activity: generation of a new integrin inhibitor.
AB  - We investigated the interaction between the urokinase receptor (uPAR) and the
      integrin alphavbeta3. Vitronectin (VN) induces cell migration by binding to
      alphavbeta3, but expression of the uPAR boosts its efficacy. Thus, uPAR may
      regulate VN-induced cell migration by interacting laterally with alphavbeta3. In
      contrast, cells expressing a uPAR mutant lacking domain 2 do not migrate in
      response to VN. This effect is overcome by D2A, a synthetic peptide derived from
      the sequence of domain 2. In addition, D2A has chemotactic activity that requires
      alphavbeta3 and activates alphavbeta3-dependent signaling pathways such as the
      Janus kinase/Stat pathway. Moreover, D2A disrupts uPAR-alphavbeta3 and uPAR
      alpha5beta1 co-immunoprecipitation, indicating that it can bind both of these
      integrins. We also identify the chemotactically active epitope harbored by
      peptide D2A. Mutating two glutamic acids into two alanines generates peptide D2A
      Ala, which lacks chemotactic activity but inhibits VN-, FN-, and collagen
      dependent cell migration. In fact, the GEEG peptide has potent chemotactic
      activity, and the GAAG sequence has inhibitory capacities. In summary, we have
      identified an integrin-interacting sequence located in domain 2 of uPAR, which is
      also a new chemotactic epitope that can activate alphavbeta3-dependent signaling
      pathways and stimulate cell migration. This sequence thus plays a pivotal role in
      the regulation of uPAR-integrin interactions. Moreover, we describe a novel, very
      potent inhibitor of integrin-dependent cell migration.

PMID- 15863513
TI  - Rac-GAP-dependent inhibition of breast cancer cell proliferation by {beta}2
      chimerin.
AB  - beta2-Chimerin is a member of the "non-protein kinase C" intracellular receptors
      for the second messenger diacylglycerol and the phorbol esters that is yet poorly
      characterized, particularly in the context of signaling pathways involved in
      proliferation and cancer progression. beta2-Chimerin possesses a C-terminal Rac
      GAP (GTPase-activating protein) domain that accelerates the hydrolysis of GTP
      from the Rac GTPase, leading to its inactivation. We found that beta2-chimerin
      messenger levels are significantly down-regulated in human breast cancer cell
      lines as well as in breast tumors. Adenoviral delivery of beta2-chimerin into MCF
      7 breast cancer cells leads to inhibition of proliferation and G(1) cell cycle
      arrest. Mechanistic studies show that the effect involves the reduction in Rac
      GTP levels, cyclin D1 expression, and retinoblastoma dephosphorylation. Studies
      using the mutated forms of beta2-chimerin revealed that these effects were
      entirely dependent on its C-terminal GAP domain and Rac-GAP activity. Moreover,
      MCF-7 cells stably expressing active Rac (V12Rac1) but not RhoA (V14RhoA) were
      insensitive to beta2-chimerin-induced inhibition of proliferation and cell cycle
      progression. The modulation of G(1)/S progression by beta2-chimerin not only
      implies an essential role for Rac in breast cancer cell proliferation but also
      raises the intriguing possibility that diacylglycerol-regulated non-protein
      kinase C pathways can negatively impact proliferation mechanisms controlled by
      Rho GTPases.

PMID- 15863514
TI  - Identification of an acquired JAK2 mutation in polycythemia vera.
AB  - Polycythemia vera (PV) is a human clonal hematological disorder. The molecular
      etiology of the disease has not been identified. PV hematopoietic progenitor
      cells exhibit hypersensitivity to growth factors and cytokines, suggesting
      possible abnormalities in protein-tyrosine kinases and phosphatases. By
      sequencing the entire coding regions of cDNAs of candidate enzymes, we identified
      a G:C--> T:A point mutation of the JAK2 tyrosine kinase in 20 of 24 PV blood
      samples but none in 12 normal samples. The mutation has varying degrees of
      heterozygosity and is apparently acquired. It changes conserved Val(617) to Phe
      in the pseudokinase domain of JAK2 that is known to have an inhibitory role. The
      mutant JAK2 has enhanced kinase activity, and when overexpressed together with
      the erythropoietin receptor in cells, it caused hyperactivation of erythropoietin
      induced cell signaling. This gain-of-function mutation of JAK may explain the
      hypersensitivity of PV progenitor cells to growth factors and cytokines. Our
      study thus defines a molecular defect of PV.

PMID- 15863516
TI  - KATAMARI1/MURUS3 Is a novel golgi membrane protein that is required for
      endomembrane organization in Arabidopsis.
AB  - In plant cells, unlike animal and yeast cells, endomembrane dynamics appear to
      depend more on actin filaments than on microtubules. However, the molecular
      mechanisms of endomembrane-actin filament interactions are unknown. In this
      study, we isolated and characterized an Arabidopsis thaliana mutant, katamari1
      (kam1), which has a defect in the organization of endomembranes and actin
      filaments. The kam1 plants form abnormally large aggregates that consist of
      endoplasmic reticulum with actin filaments in the perinuclear region within the
      cells and are defective in normal cell elongation. Map-based cloning revealed
      that the KAM1 gene is allelic to the MUR3 gene. We demonstrate that the KAM1/MUR3
      protein is a type II membrane protein composed of a short cytosolic N-terminal
      domain and a transmembrane domain followed by a large lumenal domain and is
      localized specifically on Golgi membranes. We further show that actin filaments
      interact with Golgi stacks via KAM1/MUR3 to maintain the proper organization of
      endomembranes. Our results provide functional evidence that KAM1/MUR3 is a novel
      component of the Golgi-mediated organization of actin functioning in proper
      endomembrane organization and cell elongation.

PMID- 15863515
TI  - The cyclin-dependent kinase inhibitor KRP2 controls the onset of the
      endoreduplication cycle during Arabidopsis leaf development through inhibition of
      mitotic CDKA;1 kinase complexes.
AB  - Exit from the mitotic cell cycle and initiation of cell differentiation
      frequently coincides with the onset of endoreduplication, a modified cell cycle
      during which DNA continues to be duplicated in the absence of mitosis. Although
      the mitotic cell cycle and the endoreduplication cycle share much of the same
      machinery, the regulatory mechanisms controlling the transition between both
      cycles remain poorly understood. We show that the A-type cyclin-dependent kinase
      CDKA;1 and its specific inhibitor, the Kip-related protein, KRP2 regulate the
      mitosis-to-endocycle transition during Arabidopsis thaliana leaf development.
      Constitutive overexpression of KRP2 slightly above its endogenous level only
      inhibited the mitotic cell cycle-specific CDKA;1 kinase complexes, whereas the
      endoreduplication cycle-specific CDKA;1 complexes were unaffected, resulting in
      an increase in the DNA ploidy level. An identical effect on the endoreduplication
      cycle could be observed by overexpressing KRP2 exclusively in mitotically
      dividing cells. In agreement with a role for KRP2 as activator of the mitosis-to
      endocycle transition, KRP2 protein levels were more abundant in endoreduplicating
      than in mitotically dividing tissues. We illustrate that KRP2 protein abundance
      is regulated posttranscriptionally through CDK phosphorylation and proteasomal
      degradation. KRP2 phosphorylation by the mitotic cell cycle-specific CDKB1;1
      kinase suggests a mechanism in which CDKB1;1 controls the level of CDKA;1
      activity through regulating KRP2 protein abundance. In accordance with this
      model, KRP2 protein levels increased in plants with reduced CDKB1;1 activity.
      Moreover, the proposed model allowed a dynamical simulation of the in vivo
      observations, validating the sufficiency of the regulatory interactions between
      CDKA;1, KRP2, and CDKB1;1 in fine-tuning the mitosis-to-endocycle transition.

PMID- 15863517
TI  - Microtubule dynamics in living root hairs: transient slowing by lipochitin
      oligosaccharide nodulation signals.
AB  - The incorporation of a fusion of green fluorescent protein and tubulin-alpha 6
      from Arabidopsis thaliana in root hairs of Lotus japonicus has allowed us to
      visualize and quantify the dynamic parameters of the cortical microtubules in
      living root hairs. Analysis of individual microtubule turnover in real time
      showed that only plus polymer ends contributed to overall microtubule dynamicity,
      exhibiting dynamic instability as the main type of microtubule behavior in Lotus
      root hairs. Comparison of the four standard parameters of in vivo dynamic
      instability--the growth rate, the disassembly rate, and the frequency of
      transitions from disassembly to growth (rescue) and from growth to disassembly
      (catastrophe)--revealed that microtubules in young root hairs were more dynamic
      than those in mature root hairs. Either inoculation with Mesorhizobium loti or
      purified M. loti lipochitin oligosaccharide signal molecules (Nod factors)
      significantly affected the growth rate and transition frequencies in emerging and
      growing root hairs, making microtubules less dynamic at a specific window after
      symbiotic inoculation. This response of root hair cells to rhizobial Nod factors
      is discussed in terms of the possible biological significance of microtubule
      dynamics in the early signaling events leading to the establishment and
      progression of the globally important Rhizobium/legume symbiosis.

PMID- 15863519
TI  - Destination-selective long-distance movement of phloem proteins.
AB  - The phloem macromolecular transport system plays a pivotal role in plant growth
      and development. However, little information is available regarding whether the
      long-distance trafficking of macromolecules is a controlled process or passive
      movement. Here, we demonstrate the destination-selective long-distance
      trafficking of phloem proteins. Direct introduction, into rice (Oryza sativa), of
      phloem proteins from pumpkin (Cucurbita maxima) was used to screen for the
      capacity of specific proteins to move long distance in rice sieve tubes. In our
      system, shoot-ward translocation appeared to be passively carried by bulk flow.
      By contrast, root-ward movement of the phloem RNA binding proteins 16-kD C.
      maxima phloem protein 1 (CmPP16-1) and CmPP16-2 was selectively controlled. When
      CmPP16 proteins were purified, the root-ward movement of CmPP16-1 became
      inefficient, suggesting the presence of pumpkin phloem factors that are
      responsible for determining protein destination. Gel-filtration chromatography
      and immunoprecipitation showed that CmPP16-1 formed a complex with other phloem
      sap proteins. These interacting proteins positively regulated the root-ward
      movement of CmPP16-1. The same proteins interacted with CmPP16-2 as well and did
      not positively regulate its root-ward movement. Our data demonstrate that, in
      addition to passive bulk flow transport, a destination-selective process is
      involved in long-distance movement control, and the selective movement is
      regulated by protein-protein interaction in the phloem sap.

PMID- 15863520
TI  - The yeast Saccharomyces cerevisiae is not an efficient tool for in vivo studies
      of plant vacuolar sorting receptors.

PMID- 15863521
TI  - Breakable stent for interventions in infants and neonates: an animal study and
      histopathological findings.
AB  - OBJECTIVE: To test in a neonatal animal model the feasibility and
      biocompatibility of a new breakable stent that can be broken open by balloon
      dilatation during reintervention for use in neonates and infants. MATERIALS AND
      METHODS: Medical grade stainless steel breakable stents (n = 16) were
      interventionally implanted in systemic arteries in neonatal piglets (n = 7).
      Patency of the stented segments was shown by repeated angiography. Stents were
      redilated up to three times. After a follow up of 18-165 days the animals were
      killed and the tissue block containing the stent was excised. Besides standard
      histological examination, scanning electron microscopy was used for
      biocompatibility screening. RESULTS: The stents were broken by redilatation with
      a conventional angioplasty balloon catheter. During follow up, patency of all
      stented segments was shown angiographically. One stent became dislocated during
      implantation. One vessel ruptured during redilatation when an inadequately large
      balloon catheter was used for dilatation. No other complications were observed.
      Scanning electron microscopy showed complete cellular coverage of the stent
      struts. Histological examination showed thinning of the vessel wall and partial
      rupture of the media at the site of stent breakage. An only mild inflammatory
      reaction was detected. CONCLUSION: The new breakable stent can be broken open by
      simple angioplasty. Feasibility, effectiveness, and biocompatibility were shown
      in an animal model. Surgery to remove stents from paediatric patients due to
      disproportion between a previously implanted stent and the growing vessel may be
      avoided by the use of a breakable stent.

PMID- 15863518
TI  - A tiling microarray expression analysis of rice chromosome 4 suggests a
      chromosome-level regulation of transcription.
AB  - The complete genome sequence of cultivated rice (Oryza sativa) provides an
      unprecedented opportunity to understand the biology of this model cereal. An
      essential and necessary step in this effort is the determination of the coding
      information and expression patterns of each sequenced chromosome. Here, we report
      an analysis of the transcriptional activity of rice chromosome 4 using a tiling
      path microarray based on PCR-generated genomic DNA fragments. Six representative
      rice organ types were examined using this microarray to catalog the transcribed
      regions of rice chromosome 4 and to reveal organ- and developmental stage
      specific transcription patterns. This analysis provided expression support for
      82% of the gene models in the chromosome. Transcriptional activities in 1643
      nonannotated regions were also detected. Comparison with cytologically defined
      chromatin features indicated that in juvenile-stage rice the euchromatic region
      is more actively transcribed than is the transposon-rich heterochromatic portion
      of the chromosome. Interestingly, increased transcription of transposon-related
      gene models in certain heterochromatic regions was observed in mature-stage rice
      organs and in suspension-cultured cells. These results suggest a close
      correlation between transcriptional activity and chromosome organization and the
      developmental regulation of transcription activity at the chromosome level.

PMID- 15863522
TI  - Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in
      patients with coronary heart disease.
AB  - OBJECTIVES: To investigate whether sildenafil citrate, a selective
      phosphodiesterase type 5 inhibitor, may improve endothelial vasomotor and
      fibrinolytic function in patients with coronary heart disease. DESIGN: Randomised
      double blind placebo controlled crossover study. PATIENTS AND METHODS: 16 male
      patients with coronary heart disease and eight matched healthy men received
      intravenous sildenafil or placebo. Bilateral forearm blood flow and fibrinolytic
      parameters were measured by venous occlusion plethysmography and blood sampling
      in response to intrabrachial infusions of acetylcholine, substance P, sodium
      nitroprusside, and verapamil. MAIN OUTCOME MEASURES: Forearm blood flow and acute
      release of tissue plasminogen activator. RESULTS: Mean arterial blood pressure
      fell during sildenafil infusion from a mean (SEM) of 92 (1) to 82 (1) mm Hg in
      patients and from 94 (1) to 82 (1) mm Hg in controls (p < 0.001 for both).
      Sildenafil increased endothelium independent vasodilatation with sodium
      nitroprusside (p < 0.05) but did not alter the blood flow response to
      acetylcholine or verapamil in patients or controls. Substance P caused a dose
      dependent increase in plasma tissue plasminogen activator antigen concentrations
      (p < 0.01) that was unaffected by sildenafil in either group. CONCLUSIONS:
      Sildenafil does not improve peripheral endothelium dependent vasomotor or
      fibrinolytic function in patients with coronary heart disease. Phosphodiesterase
      type 5 inhibitors are unlikely to reverse the generalised vascular dysfunction
      seen in patients with coronary heart disease.

PMID- 15863523
TI  - Decline in incidence of hospitalisation for acute myocardial infarction in the
      Netherlands from 1995 to 2000.
AB  - OBJECTIVE: To study the change in incidence of hospitalisation for a first acute
      myocardial infarction (AMI) in the Netherlands from 1995 to 2000. METHODS:
      Patients hospitalised with their first AMI in the Netherlands in 1995 and 2000
      were identified through linkage of the national hospital discharge register and
      the population register. RESULTS: 21,565 patients hospitalised for their first
      AMI in 1995 and 19,058 patients hospitalised for their first AMI in 2000 were
      identified. In both years, the age specific incidence of hospitalisation for a
      first AMI was higher in men than in women and increased with age (up to 90
      years). In both men and women, the age standardised incidence was lower in 2000
      than in 1995, a decline of 19% (95% confidence interval 17% to 21%) and 17% (95%
      confidence interval 14% to 19%), respectively. CONCLUSIONS: Our study provides
      the first nationwide incidence estimates of first AMI in the Netherlands. From
      1995 to 2000, the risk of AMI declined considerably.

PMID- 15863527
TI  - Can postmenopausal women patch up their sex lives with testosterone?

PMID- 15863528
TI  - Medical liability and patient safety: setting the proper course.

PMID- 15863529
TI  - Testosterone patch for low sexual desire in surgically menopausal women: a
      randomized trial.
AB  - OBJECTIVE: To assess the efficacy and safety of a 300 mug/d testosterone patch
      for the treatment of hypoactive sexual desire disorder in surgically menopausal
      women on concomitant estrogen therapy. METHODS: Five hundred thirty-three women
      with hypoactive sexual desire disorder who had undergone previous hysterectomy
      and bilateral oophorectomy were enrolled in a 24-week, multicenter, double-blind,
      placebo-controlled trial. Patients were randomly assigned to receive placebo or
      the testosterone patch twice weekly. The primary efficacy endpoint was change
      from baseline at week 24 in the frequency of total satisfying sexual activity,
      measured by the Sexual Activity Log. Secondary measures included sexual desire
      using the Profile of Female Sexual Function and personal distress as measured by
      the Personal Distress Scale. Hormone levels, adverse events, and clinical
      laboratory measures were reviewed. RESULTS: Total satisfying sexual activity
      significantly improved in the testosterone patch group compared with placebo
      after 24 weeks (mean change from baseline, 1.56 compared with 0.73 episodes per 4
      weeks, P = .001). Treatment with the testosterone patch also significantly
      improved sexual desire (mean change, 10.57 compared with 4.29, P < .001) and
      decreased personal distress (P = .009). Serum free, total, and bioavailable
      testosterone concentrations increased from baseline. Overall, adverse events were
      similar in both groups (P > .05). The incidence of androgenic adverse events was
      higher in the testosterone group; most androgenic adverse events were mild.
      CONCLUSION: In surgically menopausal women with hypoactive sexual desire
      disorder, a 300 mug/d testosterone patch significantly increased satisfying
      sexual activity and sexual desire, while decreasing personal distress, and was
      well tolerated through up to 24 weeks of use.

PMID- 15863530
TI  - Transdermal drug delivery: clinical considerations for the obstetrician
      gynecologist.
AB  - INTRODUCTION: The first transdermal drug delivery system was introduced in the
      United States over 20 years ago. Created as an alternative route of
      administration to improve patient compliance as well as to reduce side effects,
      the transdermal delivery of drugs now represents a $1.5 to $2 billion market and
      is growing rapidly. DATA SOURCES: The medical literature from 1980 to 2005 was
      searched using the PubMed search engine. The search term was "transdermal,"
      limited to human clinical trials. Abstracts were used to identify clinical trials
      that compared transdermal preparations and their oral counterparts in the same
      study. TABULATION, INTEGRATION, AND RESULTS: In this article, we review the
      rationale for the transdermal administration of drugs; discuss aspects of the
      anatomy and physiology of the skin relevant to drug transport; examine the
      qualities required for a drug to be a good candidate for transdermal delivery;
      and consider key principles for the evaluation of the relative benefits of
      transdermal delivery, using studies of hormone replacement therapy and oral
      contraceptive as examples. CONCLUSION: The data reviewed here suggest that
      certain clinical situations support the use of the transdermal administration of
      drugs over their oral counterparts.

PMID- 15863531
TI  - Prior cesarean and the risk for placenta previa on second-trimester
      ultrasonography.
AB  - OBJECTIVE: To determine whether the increased risk of placenta previa at delivery
      in patients with a prior cesarean results from an increased risk of abnormal
      implantation or a lower likelihood of resolution. METHODS: A hospital-based, case
      control study was performed. Cases were defined as singleton pregnancies with a
      placenta previa on second-trimester ultrasonography. Controls, chosen randomly
      from patients without a placenta previa on second-trimester ultrasonography, were
      matched 3:1 with cases. Odds ratios (OR) were calculated, controlling for other
      independent risk factors for previa: age, parity, race, and smoking. RESULTS:
      There were 88 cases identified and 264 controls. Twenty cases (22.7%) and 35
      controls (13.3%) had a history of prior cesarean delivery. Previous cesarean
      delivery was an independent risk factor for previa on second-trimester
      ultrasonography (OR 1.92, 95% confidence interval [CI] 1.04-3.55), as was the
      number of cesareans (OR 1.62, 95% CI 1.12-2.34). However, neither retained their
      significance after adjusting for other known risk factors for previa (OR 1.50,
      95% CI 0.77-2.92, and OR 1.40, 95% CI 0.93-2.10, respectively). At delivery, a
      history of cesarean was associated with a 3-fold increased risk of previa.
      CONCLUSION: A previous cesarean delivery did not increase the odds for detecting
      a placenta previa on second-trimester ultrasonography. At delivery, a previous
      cesarean was associated with a previa, suggesting a lower likelihood of
      resolution.

PMID- 15863532
TI  - Subcutaneous tissue reapproximation, alone or in combination with drain, in obese
      women undergoing cesarean delivery.
AB  - OBJECTIVE: To compare the efficacy of subcutaneous suture reapproximation alone
      with suture plus subcutaneous drain for the prevention of wound complications in
      obese women undergoing cesarean delivery. METHODS: We conducted a multicenter
      randomized trial of women undergoing cesarean delivery. Consenting women with 4
      cm or more of subcutaneous thickness were randomized to either subcutaneous
      suture closure alone (n = 149) or suture plus drain (n = 131). The drain was
      attached to bulb suction and removed at 72 hours or earlier if output was less
      than 30 mL/24 h. The primary study outcome was a composite wound morbidity rate
      (defined by any of the following: subcutaneous tissue dehiscence, seroma,
      hematoma, abscess, or fascial dehiscence). RESULTS: From April 2001 to July 2004,
      a total of 280 women were enrolled. Ninety-five percent of women (268/280) had a
      follow-up wound assessment. Both groups were similar with respect to age, race,
      parity, weight, cesarean indication, diabetes, steroid/antibiotic use,
      chorioamnionitis, and subcutaneous thickness. The composite wound morbidity rate
      was 17.4% (25/144) in the suture group and 22.7% (28/124) in the suture plus
      drain group (relative risk 1.3, 95% confidence interval 0.8-2.1). Individual
      wound complication rates, including subcutaneous dehiscence (15.3% versus 21.8%),
      seroma (9.0% versus 10.6%), hematoma (2.2% versus 2.4%), abscess (0.7% versus
      3.3%), fascial dehiscence (1.4% versus 1.7%), and hospital readmission for wound
      complications (3.5% versus 6.6%), were similar (P > .05) between women treated
      with suture alone and those treated with suture plus drain, respectively.
      CONCLUSION: The additional use of a subcutaneous drain along with a standard
      subcutaneous suture reapproximation technique is not effective for the prevention
      of wound complications in obese women undergoing cesarean delivery.

PMID- 15863533
TI  - Changes in fetal position during labor and their association with epidural
      analgesia.
AB  - OBJECTIVE: To evaluate whether epidural analgesia is associated with a higher
      rate of abnormal fetal head position at delivery. METHODS: We conducted a
      prospective cohort study of 1,562 women to evaluate changes in fetal position
      during labor by using serial ultrasound examinations. Ultrasound examinations
      were performed at enrollment, epidural administration, 4 hours after the initial
      ultrasonography if epidural had not been administered, and late in labor (> 8
      cm). Information about fetal head position at delivery was obtained from the
      provider. RESULTS: Regardless of fetal head position at enrollment (occiput
      transverse, occiput posterior, or occiput anterior), most fetuses were occiput
      anterior at delivery (enrollment position: occiput transverse 78%, occiput
      posterior 80%, occiput anterior 83%, P = .1). Final fetal position was
      established close to delivery. Of fetuses that were occiput posterior late in
      labor, only 20.7% were occiput posterior at delivery. Changes in fetal head
      position were common, and 36% of women had an occiput posterior fetus on at least
      one ultrasound examination. Women receiving epidural did not have more occiput
      posterior fetuses at the enrollment (23.4% epidural versus 26.0 no epidural, P =
      .9) or the epidural/4-hour ultrasound examination (24.9% epidural, 28.3% no
      epidural), but did have more occiput posterior fetuses at delivery (12.9%
      epidural versus 3.3% no epidural, P = .002); the association remained in a
      multivariate model (adjusted odds ratio 4.0, 95% confidence interval 1.4-11.1).
      CONCLUSION: Fetal position changes are common during labor, with the final fetal
      position established close to delivery. Our demonstration of a strong association
      of epidural with fetal occiput posterior position at delivery represents a
      mechanism that may contribute to the lower rate of spontaneous vaginal delivery
      consistently observed with epidural.

PMID- 15863534
TI  - Impact of maternal age on obstetric outcome.
AB  - OBJECTIVE: To estimate the effect of maternal age on obstetric outcomes. METHODS:
      A prospective database from a multicenter investigation of singletons, the FASTER
      trial, was studied. Subjects were divided into 3 age groups: 1) less than 35
      years, 2) 35-39 years, and 3) 40 years and older. Multivariable logistic
      regression analysis was used to assess the effect of age on outcomes after
      adjusting for race, parity, body mass index, education, marital status, smoking,
      medical history, use of assisted conception, and patient's study site. RESULTS: A
      total of 36,056 women with complete data were available: 28,398 (79%) less than
      35 years of age; 6,294 (17%) 35-39 years; and 1,364 (4%) 40 years and older.
      Increasing age was significantly associated with miscarriage (adjusted odds ratio
      [adjOR]2.0 and 2.4 for ages 35-39 years and age 40 years and older,
      respectively), chromosomal abnormalities (adjOR 4.0 and 9.9), congenital
      anomalies (adjOR 1.4 and 1.7), gestational diabetes (adjOR 1.8 and 2.4), placenta
      previa (adjOR 1.8 and 2.8), and cesarean delivery (adjOR 1.6 and 2.0). Patients
      aged 35-39 years were at increased risk for macrosomia (adjOR 1.4). Increased
      risk for abruption (adjOR 2.3), preterm delivery (adjOR 1.4), low birth weight
      (adjOR 1.6), and perinatal mortality (adjOR 2.2) was noted in women aged 40 years
      and older. CONCLUSION: Increasing maternal age is independently associated with
      specific adverse pregnancy outcomes. Increasing age is a continuum rather than a
      threshold effect.

PMID- 15863535
TI  - Brief intervention for prenatal alcohol use: a randomized trial.
AB  - OBJECTIVE: To test the effectiveness of a brief intervention in the reduction of
      prenatal alcohol consumption by women when a partner is included. METHODS:
      Randomized trial of a single session brief intervention given by the study nurse
      or principal investigator for 304 pregnant women and their partners. The women
      had positive T-ACE (Tolerance, Annoyed, Cut down, Eye-opener, an alcohol
      screening test) results and were at risk for alcohol consumption while pregnant.
      All completed initial diagnostic and postpartum interviews. RESULTS: Fewer than
      20% of participants (median 11.5 weeks of gestation) were abstinent at study
      enrollment, averaging more than 1.5 drinks per episode. Nearly 30% had 2 or more
      drinks at a time while pregnant. Prenatal alcohol use declined in both the
      treatment and control groups after study enrollment, based on a 95% follow-up
      rate. Factors associated with increased prenatal alcohol use after randomization
      included more years of education, extent of previous alcohol consumption, and
      temptation to drink in social situations. Brief interventions for prenatal
      alcohol reduced subsequent consumption most significantly for the women with the
      highest consumption initially (regression coefficient, b = -0.163, standard error
      (b) = 0.063, P < .01). Moreover, the effects of the brief intervention were
      significantly enhanced when a partner participated (b = -0.932, standard error
      (b) = 0.468), P < .05). CONCLUSION: Pregnant women with the highest levels of
      alcohol use reduced their drinking most after a brief intervention that included
      their partners. Recommendations include consistent screening for prenatal alcohol
      use followed by diagnostic assessment when indicated, and if confirmed by other
      studies, a patient-partner brief intervention for the heaviest drinkers.

PMID- 15863536
TI  - Lower urinary tract symptoms and pelvic floor muscle exercise adherence after 15
      years.
AB  - OBJECTIVE: Pelvic floor muscle training effectively treats female stress urinary
      incontinence. However, data on long-term efficacy and adherence are sparse. Our
      aims were to assess current lower urinary tract symptoms and exercise adherence
      15 years after ending organized training. METHODS: Originally, 52 women with
      urodynamic stress urinary incontinence were randomly assigned to home or
      intensive exercise. After 6 months, 60% in the intensive group were almost or
      completely continent, compared with 17% in the home group. Fifteen years later,
      all original study subjects were invited to complete a postal questionnaire
      assessing urinary symptoms (using validated outcome tools) and current pelvic
      floor muscle training. RESULTS: Response rate was 90.4%. There were no
      differences in any urinary outcomes or satisfaction between the 2 study groups as
      a whole or when restricted to those without intervening stress urinary
      incontinence surgery. One half of both groups had stress urinary incontinence
      surgery during the 15-year follow-up period. Twenty-eight percent performed
      pelvic floor muscle training at least weekly; this rate did not differ by
      original group assignment or operated status. More operated women reported severe
      incontinence (P = .03) and leakage that interfered with daily life (P = .04) than
      did nonoperated women. There were no other differences between operated and
      nonoperated women. CONCLUSION: The marked benefit of intensive pelvic floor
      muscle training seen short-term was not maintained 15 years later. Long-term
      adherence to training is low. Urinary symptoms were equally common in both
      operated and nonoperated women. Further studies are needed to understand factors
      associated with long-term effectiveness of stress urinary incontinence
      treatments.

PMID- 15863537
TI  - Low-molecular-weight heparin (dalteparin) in women with gynecologic malignancy.
AB  - OBJECTIVE: To compare the efficacy of dalteparin, a low-molecular-weight heparin,
      to unfractionated heparin (UFH) in the prevention of deep venous thrombosis (DVT)
      and pulmonary embolism in patients after surgery for gynecologic malignancy.
      METHODS: The medical records of all patients undergoing major surgery on the
      Gynecologic Oncology Service at the Massachusetts General Hospital from July 2002
      through April 2003 were reviewed. Patients with confirmed malignancy were
      included. Between July 1, 2002, and November 15, 2002, dalteparin (5,000 U
      subcutaneously each day) was used for postoperative prophylaxis for DVT and
      pulmonary embolus. After November 15, 2002, the method of prophylaxis was changed
      to UFH (5,000 U subcutaneously every 8 hours) exclusively. Patients were
      evaluated for DVT or pulmonary embolus based on clinical suspicion using computed
      tomographic angiography, ventilation and perfusion scan, or lower extremity
      doppler. RESULTS: A total of 214 patients were identified who met study criteria.
      Dalteparin was administered to 103 patients, and UFH was administered to 111. The
      rates of clinically significant DVT or pulmonary embolus in patients receiving
      dalteparin and UFH were 8.9% and 1.2%, respectively (P = .009). Major risk
      factors for DVT or pulmonary embolus, including age, obesity, duration of
      surgery, and type of malignancy, did not differ between groups. There were no
      significant differences in bleeding complications or transfusion requirements
      between groups. CONCLUSION: The low-molecular-weight heparin dalteparin dosed
      5,000 U daily is inadequate postoperative prophylaxis in women undergoing surgery
      for gynecologic cancer. In addition, heparin administered every 8 hours was not
      associated with increased bleeding complications. The use of dalteparin at the
      doses used in this study should be questioned until a large randomized trial
      shows efficacy in these high-risk patients.

PMID- 15863538
TI  - Vaginal thickness, cross-sectional area, and perimeter in women with and those
      without prolapse.
AB  - OBJECTIVE: Use axial magnetic resonance imaging to test the null hypothesis that
      no difference exists in apparent vaginal thickness between women with and those
      without prolapse. METHODS: Magnetic resonance imaging studies of 24 patients with
      prolapse at least 2 cm beyond the introitus were selected from an ongoing study
      comparing women with prolapse with normal control subjects. The magnetic
      resonance scans of 24 women with prolapse (cases) and 24 women without prolapse
      (controls) were selected from those of women of similar age, race, and parity.
      The magnetic resonance files were imported into an experimental modeling program,
      and 3-dimensional models of each vagina were created. The minimum transverse
      plane cross-sectional area, mid-sagittal plane diameter, and transverse plane
      perimeter of each vaginal model were calculated. RESULTS: Neither the mean age
      (cases 58.6 years +/- standard deviation [SD] 14.4 versus controls 59.4 years +/-
      SD 13.2) nor the mean body mass index (cases 24.1 kg/m(2)+/- SD 3.3, controls
      25.7 kg/m(2)+/- SD 3.7) differed significantly between groups. Minimum mid
      sagittal vaginal diameters did not differ between groups. Patients with prolapse
      had larger minimum vaginal cross-sectional areas than controls (5.71 cm(2)+/-
      standard error of the mean [SEM] 0.25 versus 4.76 cm(2)+/- SEM 0.20,
      respectively; P = .005). The perimeter of the vagina was also larger in the
      prolapse group (11.10 cm +/- SEM 0.24) compared with controls (9.96 cm +/- SEM
      0.22) P = .001. Subgroup analysis of patients with endogenous or exogenous
      estrogen showed prolapse patients had larger vaginal cross-sectional area (P =
      .030); in patients without estrogen group differences were not significant (P =
      .099). CONCLUSION: Vaginal thickness is similar in women with and those without
      pelvic organ prolapse. The vaginal perimeter and cross-sectional areas are 11%
      and 20% larger in prolapse patients, respectively. Estrogen status did not affect
      differences found between groups.

PMID- 15863539
TI  - Vulvar granuloma fissuratum: a description of fissuring of the posterior
      fourchette and the repair.
AB  - OBJECTIVE: To describe the characteristics of women who experience chronic
      fissuring of the posterior fourchette and the outcome of treatment administered.
      METHODS: We conducted a retrospective review of 42 women with granuloma
      fissuratum presenting for care between January 1, 1995, and December 31, 2003.
      Women underwent medical management first, and if improvement was minimal,
      perineoplasty was recommended. Dyspareunia and vulvar symptom scores, including
      itching, burning, and pain, before and after treatment were compared. RESULTS:
      Twenty women were managed nonoperatively, while 22 women underwent perineoplasty.
      The median age at diagnosis of granuloma fissuratum was 42.5 years (range 26-78).
      The fissure resolved in 13 of 20 women (65%) who were managed nonoperatively and
      in 21 of 22 women (95%) who underwent perineoplasty. Of the 11 women sexually
      active after perineoplasty, all had preoperative dyspareunia; it resolved in 7
      (64%) women. Among the 13 women managed nonsurgically who had resolution of the
      fissure, 7 women were sexually active after treatment and dyspareunia resolved in
      2 (29%) women. Other vulvar symptoms, such as burning, itching, pain, and
      discharge, showed no significant improvement after either surgical or nonsurgical
      treatment. CONCLUSION: Although fissuring is common with some vulvar dermatoses,
      such as lichen sclerosus and contact vulvitis, and often resolves with the
      appropriate medical management, fissuring may also occur as a primary finding and
      may benefit from perineoplasty.

PMID- 15863540
TI  - Preoperative vaginal preparation with povidone-iodine and the risk of
      postcesarean endometritis.
AB  - OBJECTIVE: Postcesarean endometritis and wound infection remain significant
      morbidities, despite use of strategies to prevent these complications. We
      investigated the effect of preoperative vaginal preparation with povidone-iodine
      as a preventive intervention against postcesarean endometritis and wound
      infection. METHODS: A randomized controlled study was performed in 308 women
      undergoing nonemergent cesarean delivery. Subjects received either standard
      abdominal scrub alone or abdominal scrub with an additional vaginal preparation
      with povidone-iodine solution. All subjects received prophylactic antibiotic at
      the time of umbilical cord clamping. Each subject's postoperative course was
      reviewed for development of febrile morbidity (temperature > 38.0 degrees C),
      endometritis (temperature > 38.4 degrees C accompanied by fundal tenderness
      occurring beyond the first postoperative day, in the absence of evidence of other
      infection), and wound infection. RESULTS: Postcesarean endometritis occurred in
      7.0% of subjects who received a preoperative vaginal preparation and 14.5% of
      controls (P < .05). There was no measurable effect of a vaginal scrub on the
      development of postoperative fever or wound infection. The adjusted odds ratio
      for developing endometritis after a vaginal preparation was 0.44 (95% confidence
      interval [CI] 0.193-0.997). Multivariate analysis showed an increased risk of
      developing endometritis in association with severe anemia (adjusted OR 4.26, 95%
      CI 1.568-11.582), use of intrapartum internal monitors (adjusted OR 2.84, 95% CI
      1.311-6.136), or history of antenatal genitourinary infection (adjusted OR 2.9,
      95% CI 1.265-6.596). CONCLUSION: Preoperative vaginal scrub with povidone-iodine
      decreases the incidence of postcesarean endometritis. This intervention does not
      seem to decrease the overall risk of postoperative fever or wound infection.

PMID- 15863542
TI  - The incidence of large fetomaternal hemorrhage and the Kleihauer-Betke test.
AB  - OBJECTIVE: To assess the frequency of large fetomaternal hemorrhage and to
      estimate its incidence in cesarean compared with vaginal deliveries. METHODS: In
      this prospective cohort study, the study group was composed of 313 women who
      underwent cesarean delivery. Control subjects were 253 women who delivered
      vaginally and were matched for age, parity, ethnic origin, and gestational age.
      Ninety-six pregnant women at term, but before delivery (prelabor group), were
      also included to determine whether delivery itself is the cause of fetomaternal
      hemorrhage. Fetomaternal hemorrhage was measured by using the Kleihauer-Betke
      test. RESULTS: Twenty women (6.4%) in the study group and 17 (6.7%) in the
      control group had a large fetomaternal hemorrhage (Kleihauer-Betke test > 0.4%).
      Five women (5.2%) in the prelabor group had a large fetomaternal hemorrhage. The
      differences were not significant. A large fetomaternal hemorrhage occurred in 14
      of 146 (9.6%) women who underwent emergency cesarean, compared with 6 of 167
      (3.5%) who delivered by elective cesarean (P = .04). In deliveries complicated by
      oligohydramnios, cord around the neck, or low birth weight, a higher rate of
      large fetomaternal hemorrhage was seen. CONCLUSION: Our results indicate a rate
      of large fetomaternal hemorrhage that is substantially higher than previously
      reported, with no difference between vaginal and cesarean deliveries. This may
      reflect inaccuracies with the current method used to estimate the degree of
      fetomaternal hemorrhage.

PMID- 15863541
TI  - Cause and effect analysis of closed claims in obstetrics and gynecology.
AB  - BACKGROUND: Identifying the etiologies of real or perceived adverse clinical
      events and undesired outcomes is an important step in improving patient safety
      and reducing malpractice risks. Systematic analysis of obstetrics and gynecology
      related risk management files allows a more complete examination of ways that
      human and systems factors may contribute to adverse events. OBJECTIVE: To learn
      the medical complaints of patients who experienced apparent adverse events, the
      general causes of those adverse events, and the significant specific causal
      factors involved in obstetrics and gynecology-related risk management cases.
      METHODS: This was a retrospective analysis of 90 consecutive obstetrics and
      gynecology-related internal review files opened by a medical center's risk
      managers between 1995 and 2001. Each file was analyzed to identify factors that
      may have contributed to or caused unanticipated adverse events. The main outcome
      was the pattern of contributing factors when they were aggregated into
      categories. RESULTS: Fifty percent of cases were associated with inpatient
      obstetrics. Factors that may have contributed to adverse events were identified
      in 78% of cases, and most had more than one contributing factor. Thirty-one
      percent of adverse events were associated with apparent communication problems.
      Clinical performance issues were identified in 31% of cases, diagnostic issues in
      18% of cases, and patient behavior contributed to 14% of adverse events.
      CONCLUSION: Diagnostic, therapeutic, and communication issues were the most
      common factors identified. Although the generalizability of these data are
      unknown, all obstetrics and gynecology departments face multiple challenges in
      assuring consistent quality care. Analysis of claims files may help identify
      opportunities for improvement.

PMID- 15863543
TI  - High parity and fetal morbidity outcomes.
AB  - OBJECTIVE: We investigated the association between high parity and fetal
      morbidity outcomes. METHODS: We analyzed 22,463,141 singleton deliveries at 20
      weeks or more of gestation in the United States from 1989 through 2000. Adjusted
      odds ratios generated from logistic regression models were used to approximate
      relative risk for neonatal morbidity in women with 1-4 (moderate parity or type
      I; referent group), 5-9 (high parity or type II), 10-14 (very high parity or type
      III) and 15 or more (extremely high parity or type IV) prior live births. Main
      outcome measures included low and very low birth weight, preterm and very preterm
      birth, and small and large for gestational age delivery. RESULTS: The overall
      crude rates for low birth weight, very low birth weight, preterm birth, very
      preterm birth, and small and large for gestational age were 55, 11, 97, 19, 83,
      and 129 per 1,000 live births, respectively. The adjusted odds ratios for low
      birth weight, very low birth weight, preterm, and very preterm delivery increased
      consistently and in a dose-effect fashion with ascending parity (P for trend <
      .001). In the case of large for gestational age delivery, the adjusted odds ratio
      showed an inverted-U pattern, being highest among women in the type III parity
      cluster. The findings with respect to small for gestational age were
      inconclusive. CONCLUSION: High parity is a risk factor for adverse fetal
      outcomes. However, the impact of heightened parity is more manifest as shortened
      gestation rather than physical size restriction. These findings could prove
      beneficial for counseling women of high parity.

PMID- 15863544
TI  - Ectopic pregnancy rate and treatment utilization in a large managed care
      organization.
AB  - OBJECTIVE: To estimate the ectopic pregnancy rate at Kaiser Permanente, Northern
      California, during 1997-2000. METHODS: Computerized data systems covering
      inpatient, outpatient, and pharmacy records were reviewed for evidence of ectopic
      pregnancies during the study period. Denominator data were calculated from
      computerized utilization and membership data for the same period. RESULTS: We
      identified 2,617 ectopic pregnancies that occurred between 1997 and 2000 among
      126,451 reported pregnancies for an annual rate of 20.70 per 1,000 reported
      pregnancies and 1.03 per 1,000 women 15-44 years old. There was no evidence of a
      trend over time in these data. The rate increased with increasing age.
      Approximately 35% of these women were medically treated, and we observed an
      increase over time in the proportion of women who were medically treated.
      CONCLUSION: Using computerized data systems in a large integrated health delivery
      system, we found that the rate of ectopic pregnancy in 1997-2000 was similar to
      the national rate in 1990-1992, when national data were last available. These
      data suggest that the ectopic pregnancy rate is not increasing, although
      differences in the study populations need to be kept in mind. Medical treatment
      seems to be increasing over time.

PMID- 15863545
TI  - Nuchal translucency thickness in fetuses with chromosomal translocation at 11-12
      weeks of gestation.
AB  - OBJECTIVE: To investigate differences in nuchal translucency thickness among
      fetuses in which either parent is a balanced chromosome translocation carrier.
      METHODS: A prospective observational study was conducted with 98 pregnant women
      in the first trimester. Each had been advised to undergo chorionic villous
      sampling for fetal karyotyping for the indication of parental balanced
      chromosomal translocation. Fetal nuchal translucency measurement was performed
      before chorionic villous sampling. Nuchal translucency thickness was compared
      among fetuses with 3 kinds of karyotypes: normal, balanced translocation, and
      unbalanced translocation. RESULTS: There were no differences in maternal age,
      gestational age, parity, and number of previous miscarriages among pregnancies
      with normal karyotype, balanced chromosomal translocation, and unbalanced
      chromosomal translocation. A significantly greater nuchal translucency thickness
      was shown in the unbalanced chromosomal translocation group (2.9 +/- 1.2 mm)
      compared with both the balanced chromosomal translocation group (1.0 +/- 0.6 mm;
      P < .001) and the normal karyotype group (1.0 +/- 0.8 mm; P < .001). No
      statistically significant difference in nuchal translucency thickness was found
      between the balanced chromosomal translocation group and normal karyotype group
      (P = .991). Nuchal translucency thickness did not differ significantly between
      unbalanced chromosomal translocation dependent on paternal origin and that
      dependent on maternal origin (P = .611). CONCLUSION: In fetuses with unbalanced
      chromosomal translocation, nuchal translucency thickness tends to be greater, and
      thus nuchal translucency measurement might be considered part of the
      investigation for pregnancies marked by a parental balanced chromosomal
      translocation.

PMID- 15863546
TI  - Menopausal symptoms and treatment-related effects of estrogen and progestin in
      the Women's Health Initiative.
AB  - OBJECTIVE: To estimate the effects of estrogen plus progestin (E+P) therapy on
      menopausal symptoms, vaginal bleeding, gynecologic surgery rates, and treatment
      related adverse effects in postmenopausal women. METHODS: Randomized, double
      blind, placebo-controlled trial of 16,608 postmenopausal women, ages 50-79 (mean
      +/- standard deviation 63.3 +/- 7.1) years, with intact uterus, randomized to one
      tablet per day containing 0.625 mg conjugated equine estrogens plus 2.5 mg
      medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102), and followed for
      a mean of 5.6 years. Change in symptoms and treatment-related effects were
      analyzed at year 1 in all participants. Bleeding and gynecologic surgery rates
      were analyzed through study close-out. RESULTS: Baseline symptoms did not differ
      between the treatment groups. More women assigned to E+P than placebo reported
      relief of hot flushes (85.7% versus 57.7%, respectively; odds ratio 4.40; 95%
      confidence interval 3.40-5.71), night sweats (77.6% versus 57.4%; 2.58; 2.04
      3.26), vaginal or genital dryness (74.1% versus 54.6%; 2.40; 1.90-3.02), joint
      pain or stiffness (47.1% versus 38.4%; 1.43; 1.24-1.64), and general aches or
      pains (49.3% versus 43.7%; 1.25; 1.08-1.44). Women asymptomatic at baseline who
      were assigned to E+P more often developed breast tenderness (9.3% versus 2.4%,
      respectively; 4.26; 3.59-5.04), vaginal or genital discharge (4.1% versus 1.0%;
      4.47; 3.44-5.81), vaginal or genital irritation (4.2% versus 2.8%; 1.52; 1.27
      1.81), and headaches (5.8% versus 4.7%; 1.26; 1.08-1.46) than women on placebo.
      Estrogen plus progestin treatment prevented the onset of new musculoskeletal
      symptoms. Vaginal bleeding was reported by 51% of women on E+P and 5% of women on
      placebo at 6 months; most bleeding was reported as spotting. Gynecologic
      surgeries (hysterectomy and dilation and curettage) were performed more
      frequently in women assigned to E+P (3.1% versus 2.5% for hysterectomy, hazard
      ratio = 1.23, P = .026; 5.4% versus 2.4% for dilation and curettage, hazard ratio
      = 2.23, P < .001). CONCLUSION: Estrogen plus progestin relieved some menopausal
      symptoms, such as vasomotor symptoms and vaginal or genital dryness, but
      contributed to treatment-related effects, such as bleeding, breast tenderness,
      and an increased likelihood of gynecologic surgery.

PMID- 15863547
TI  - Efficacy and safety of isopropanolic black cohosh extract for climacteric
      symptoms.
AB  - OBJECTIVE: Several clinical studies suggest that black cohosh may be effective in
      climacteric complaints. However, evidence of its efficacy based on current
      quality standards has been limited. METHODS: This randomized, multicenter, double
      blind clinical trial compared the efficacy and tolerability of the isopropanolic
      black cohosh extract in the treatment of climacteric complaints compared with
      placebo. A total of 304 patients were randomly allocated to receive tablets
      corresponding to 40 mg drug or matching placebo daily for 12 weeks. The primary
      efficacy measure was the change from baseline on the Menopause Rating Scale I;
      secondary measures included changes in its subscores and safety variables.
      RESULTS: Patient groups did not differ in baseline characteristics. The
      isopropanolic black cohosh extract was more effective than placebo (P < .001)
      depending on time from symptom onset (P = .014) and follicle-stimulating hormone
      level (P = .011). The effect size was 0.03 to 0.05 Menopause Rating Scale units
      which is similar to recent hormone replacement therapy study results (0.036
      Menopause Rating Scale units) and may therefore be considered clinically
      relevant. Women in the early climacteric phase benefited more than in the late
      phase. The hot flush subscore was the most effective measure of the isopropanolic
      black cohosh extract's efficacy. There were no relevant group differences in
      adverse events, laboratory findings, or tolerability. CONCLUSION: This
      isopropanolic extract of black cohosh root stock is effective in relieving
      climacteric symptoms, especially in early climacteric women.

PMID- 15863548
TI  - Trends in preterm birth and perinatal mortality among singletons: United States,
      1989 through 2000.
AB  - OBJECTIVE: Despite the recent increase in preterm birth in the United States,
      trends in preterm birth subtypes have not been adequately examined. We examined
      trends in preterm birth among singletons following ruptured membranes, medical
      indications, and spontaneous preterm birth and evaluated the impact of these
      trends on perinatal mortality. METHODS: A population-based, retrospective cohort
      study comprising 46,375,578 women (16% blacks) who delivered singleton births in
      the United States, 1989 through 2000, was performed. Rates of preterm birth (< 37
      weeks), their subtypes, and associated perinatal mortality (stillbirths at >/= 22
      weeks plus neonatal deaths within 28 days), before and after adjustment for
      potential confounders, were derived from ecological logistic regression models.
      RESULTS: Preterm birth rates increased by 14% (95% confidence interval 13-15%)
      among whites from 8.3% to 9.4% and decreased by 15% (95% confidence interval 14
      16%) among blacks from 18.5% to 16.2% between 1989 and 2000. Among whites,
      preterm birth following ruptured membranes declined by 23%, medically indicated
      preterm birth increased by 55%, and spontaneous preterm birth increased by 3%.
      Among blacks, preterm birth following ruptured membranes declined by 37%,
      medically indicated preterm birth increased by 32%, and spontaneous preterm birth
      decreased by 27%. The largest decline in perinatal mortality among whites was
      associated with increases in medically indicated preterm birth, whereas the
      largest decline in perinatal mortality among blacks was associated with declines
      in preterm birth following ruptured membranes and spontaneous preterm birth.
      CONCLUSION: Temporal trends in preterm birth varied substantially based on
      underlying subtype and maternal race. The recent increase in medically indicated
      preterm birth was associated with a favorable reduction in perinatal mortality.

PMID- 15863549
TI  - Fetal growth assessment and neonatal birth weight in fetuses with an isolated
      single umbilical artery.
AB  - OBJECTIVE: To evaluate interval fetal growth and compare the incidence of small
      for-gestational age (SGA) newborns between fetuses with an isolated single
      umbilical artery and those with a 3-vessel umbilical cord. METHODS: A
      retrospective, case-controlled study in which 84 singleton pregnancies with an
      isolated single umbilical artery were compared with 3-vessel umbilical cord
      fetuses as the control group. RESULTS: There was no statistical difference
      between the groups in maternal demographic data, except for ethnicity and
      neonatal outcomes, respectively. The mean newborn birth weight was similar
      between the isolated single umbilical artery and the control groups, 3,268 +/-
      596 g and 3,274 +/- 627 g, respectively. The prevalence of SGA newborns was 7.1%
      (6 of 84) in the isolated single umbilical artery group and 4.8% (4 of 84) in the
      control group. An ultrasound examination demonstrated fetal growth restriction in
      50% of cases (3 of 6) in the isolated single umbilical artery group and in 25% of
      subjects (1 of 4) in the control group, respectively. CONCLUSION: Fetuses with an
      isolated single umbilical artery are at similar risk for SGA compared with
      fetuses with 3-vessel umbilical cords. It appears that antepartum serial
      ultrasound examination does not provide more information for interval fetal
      growth assessment in fetuses with an isolated single umbilical artery.

PMID- 15863550
TI  - Adnexal masses in pregnancy: surgery compared with observation.
AB  - OBJECTIVE: To estimate whether the delay of surgery impacts the risk of adverse
      maternal and fetal outcomes in patients diagnosed with an adnexal mass during
      pregnancy. METHODS: A review was performed of pregnant patients diagnosed with an
      adnexal mass 5 cm or greater in diameter. Data collected included age,
      gravity/parity, gestational age at diagnosis, and presenting symptoms. Ultrasound
      examinations were evaluated for mass size and complexity. Pregnancy outcome,
      complications, and surgical pathology were reviewed. RESULTS: Between 1990 and
      2003, 127,177 deliveries were performed at our institution. An adnexal mass 5 cm
      in diameter or greater was diagnosed in 63 (0.05%) patients. Pathologic diagnosis
      was available for 59 (94%) patients. The remaining 4 patients were lost to follow
      up and excluded from the analysis. Antepartum surgery was performed in 17
      patients (29%): 13 because of ultrasound findings that suggested malignancy and 4
      secondary to ovarian torsion. The remaining patients were observed, with surgery
      performed in the postpartum period or at time of cesarean delivery. The majority
      of masses were dermoid cysts (42%). Four patients were diagnosed with ovarian
      cancer (6.8% of masses, 0.0032% of deliveries), and one patient (1.7%) had a
      tumor of low malignant potential. Antepartum surgery due to ultrasound findings
      that caused concern was performed on all 5 women diagnosed with a malignancy or
      borderline tumor, compared with 12 (22%) of the patients with benign tumors (P <
      .01). CONCLUSION: In select cases, close observation is a reasonable alternative
      to antepartum surgery in patients with an adnexal mass during pregnancy.

PMID- 15863551
TI  - Expectant, medical, or surgical management of first-trimester miscarriage: a meta
      analysis.
AB  - OBJECTIVE: To quantify the relative benefits and harms of different management
      options for first-trimester miscarriage. DATA SOURCES: MEDLINE, EMBASE, and
      Cochrane Controlled Trials Register searches (1966 to July 2004), including
      references of retrieved articles. METHODS OF STUDY SELECTION: Randomized trials
      assigning women with first-trimester missed or incomplete miscarriage to
      surgical, medical, or expectant management were included. Primary outcomes were
      successful treatment and patient satisfaction. Secondary outcomes included
      moderate or severe bleeding, blood transfusion, emergency curettage, pelvic
      inflammatory disease, nausea, vomiting, and diarrhea. Comparisons used the risk
      difference. Between-study heterogeneity and random effects summary estimates were
      calculated. TABULATION, INTEGRATION, AND RESULTS: Complete evacuation of the
      uterus was significantly more common with surgical than medical management (risk
      difference 32.8%, number needed to treat 3, success rate of medical management
      62%) and with medical than expectant management (risk difference 49.7%, number
      needed to treat 2). Success rate with expectant management was spuriously low
      (39%) in the latter comparison. Analysis of cases with incomplete miscarriage
      only showed that medical management still had two thirds the chance to induce
      complete evacuation compared with surgical management, but it was better than
      expectant management. Data from studies that evaluated outcome at 48 hours or
      more after allocation indicated again that medical management had a better
      success rate than expectant management but a worse success rate than surgical
      management; expectant management probably had much lower success rates than
      surgical evacuation, but data were very sparse. Patient satisfaction data were
      sparse. Moderate or severe bleeding was less common with medical than expectant
      management (risk difference 3.2%) and possibly surgical management (risk
      difference 2.1%). There was a considerable amount of missing information, in
      particular for secondary outcomes. CONCLUSION: One additional success can be
      achieved among 3 women treated surgically rather than medically. Expectant
      management has had remarkably variable success rates across these studies,
      depending probably on the type of miscarriage. Greater standardization of
      outcomes should be a goal of future research.

PMID- 15863553
TI  - Do no harm: avoidance of herbal medicines during pregnancy.
AB  - Herbal medicines are regarded by the public and some health care providers as
      gentle and safe, but there is no scientific basis for that belief. The active
      ingredients of plant extracts are chemicals that are similar to those in purified
      medications, and they have the same potential to cause serious adverse effects.
      This commentary summarizes recent data on the poor quality control and toxicity
      of herbal remedies and on the pharmacologic activities of ginger, which is used
      for treatment of morning sickness. There are no rigorous scientific studies of
      the safety of dietary supplements during pregnancy, and the Teratology Society
      has stated that it should not be assumed that they are safe for the embryo or
      fetus. Obstetricians should advise women not to expose their fetuses to the risks
      of herbal medicines.

PMID- 15863552
TI  - Surrogate end points in clinical research: hazardous to your health.
AB  - Surrogate end points in clinical research pose real danger. A surrogate end point
      is an outcome measure, commonly a laboratory test, that substitutes for a
      clinical event of true importance. Resistance to activated protein C, for
      example, has been used as a surrogate for venous thrombosis in women using oral
      contraceptives. Other examples of inappropriate surrogate end points in
      contraception include the postcoital test instead of pregnancy to evaluate new
      spermicides, breakage and slippage instead of pregnancy to evaluate condoms, and
      bone mineral density instead of fracture to assess the safety of depo
      medroxyprogesterone acetate. None of these markers captures the effect of the
      treatment on the true outcome. A valid surrogate end point must both correlate
      with and accurately predict the outcome of interest. Although many surrogate
      markers correlate with an outcome, few have been shown to capture the effect of a
      treatment (for example, oral contraceptives) on the outcome (venous thrombosis).
      As a result, thousands of useless and misleading reports on surrogate end points
      litter the medical literature. New drugs have been shown to benefit a surrogate
      marker, but, paradoxically, triple the risk of death. Thousands of patients have
      died needlessly because of reliance on invalid surrogate markers. Researchers
      should avoid surrogate end points unless they have been validated; that requires
      at least one well done trial using both the surrogate and true outcome. The
      clinical maxim that "a difference to be a difference must make a difference"
      applies to research as well. Clinical research should focus on outcomes that
      matter.

PMID- 15863554
TI  - What obstetrics and gynecology means to me.

PMID- 15863555
TI  - The recruitment phoenix: strategies for attracting medical students into
      obstetrics and gynecology.
AB  - In less than a decade, the popularity of obstetrics and gynecology as a career
      choice has declined significantly. The American College of Obstetricians and
      Gynecologists (ACOG) and the Association of Professors of Gynecology and
      Obstetrics (APGO) are working to develop a multifaceted approach aimed at
      reversing this trend. We report on the findings and action plan developed by the
      ACOG Medical Student Recruitment Task Force as well as the current activities of
      APGO related to recruitment. Strategies include improving the quality of the
      medical student clerkship, frankly addressing gender and lifestyle issues that
      dissuade students from choosing obstetrics and gynecology as a career, and
      engaging students early in their medical school careers through student interest
      groups and mentoring programs.

PMID- 15863556
TI  - 17 hydroxyprogesterone for the prevention of preterm delivery.
AB  - The recent publication of 2 large randomized trials of 17 alpha
      hydroxyprogesterone caproate (17P) and progesterone suppositories, respectively,
      for the prevention of premature labor have renewed interest in the use of
      progesterone to prevent preterm birth. The results of these trials have
      reinforced the positive results of earlier smaller trials of 17P to prevent
      preterm delivery. A large body of evidence attests to the lack of teratogenic
      effects of 17P in pregnancy. Although progesterone is known to have many actions
      beneficial to the maintenance of pregnancy, the exact mode of action of 17P
      therapy in preventing preterm labor and delivery is not known. Current evidence
      supports the use of 17P treatment, begun early in the second trimester of
      gestation and continued weekly until 36 weeks, for women with a history of a
      previous spontaneous preterm delivery. At present no evidence exists for the use
      of 17P to prevent preterm delivery in women with multiple gestation, a short
      uterine cervix, or other high-risk conditions. The use of 17P or other progestins
      should not be encouraged for these indications outside of randomized trials. At
      present no evidence exists for the efficacy of any oral progesterone compound in
      preventing preterm labor. Four trials reporting the use of a progestational drug
      in patients with symptoms of preterm labor found no efficacy in prolonging
      pregnancy, and the use of 17P or other progestational drugs as tocolytic therapy
      should not be encouraged.

PMID- 15863557
TI  - Topiramate (topamax) for prevention of migraine.

PMID- 15863558
TI  - Treatment of menopausal vasomotor symptoms.

PMID- 15863559
TI  - Initial therapy of hypertension.

PMID- 15863560
TI  - Melissa Rowland and the rights of pregnant women.

PMID- 15863561
TI  - Melissa Rowland and the rights of pregnant women.

PMID- 15863562
TI  - Regarding Plan B: science and politics cannot be separated.

PMID- 15863566
TI  - World Health Organization systematic review of screening tests for preeclampsia.

PMID- 15863568
TI  - What obstetrics and gynecology means to me.

PMID- 15863569
TI  - ACOG Practice Bulletin. No. 62: Intrapartum fetal heart rate monitoring.

PMID- 15863570
TI  - Polyuria and pregnancy: its cause, its danger.

PMID- 15863571
TI  - Diabetes insipidus in the third trimester of pregnancy.
AB  - BACKGROUND: Transient diabetes insipidus may rarely present during late pregnancy
      and/or the immediate puerperium, and if unrecognized, may cause neurologic injury
      and threaten the lives of mother and fetus. However, when recognized early and
      treatment is initiated with desmopressin acetate, an analog of vasopressin that
      is resistant to vasopressinase, water loss in the urine is eliminated and
      complications may be abrogated. This report aims to increase the awareness of
      this disorder and describes appropriate treatment. CASES: Two cases of diabetes
      insipidus, believed to be due to excess vasopressinase, are presented to
      demonstrate the clinical features, pathogenesis, and treatment of this syndrome.
      CONCLUSION: Awareness of the syndrome of transient diabetes insipidus may lead to
      early diagnosis and appropriate treatment that will reduce the risks of maternal
      and fetal morbidity.

PMID- 15863572
TI  - Uterine cavity synechiae after hemostatic square suturing technique.
AB  - BACKGROUND: A number of surgical techniques to control severe bleeding at
      cesarean delivery have been proposed, such as uterine artery ligation,
      hypogastric artery ligation, and uterine compression suturing. CASE: A
      primigravida with severe postpartum hemorrhage and disseminated intravascular
      coagulopathy had multiple square sutures placed through the uterus. Serial
      sonographic follow-up studies revealed uterine synechiae with partial obstruction
      of menstrual flow. Hysteroscopy confirmed unabsorbed sutures in the uterine
      cavity. CONCLUSION: The use of multiple sutures through the uterus is effective
      to control postpartum hemorrhage but may lead to uterine synechiae.

PMID- 15863573
TI  - Pregnancy complicated by uterine synechiae after endometrial ablation.
AB  - BACKGROUND: The use of endometrial ablation is becoming more common in the
      treatment of abnormal uterine bleeding. As a result, an increasing number of
      reproductive-aged women are electing to have an endometrial ablation. Women who
      undergo this procedure should be informed that desired fertility is a
      contraindication because endometrial ablation can significantly increase the risk
      of obstetric complications. This is the first reported pregnancy complicated by
      uterine synechiae in a patient with a history of an endometrial ablation (MEDLINE
      search, January 1985 to June 2004, key words "pregnancy," "obstetric,"
      "endometrial ablation," "complications," and "hysteroscopy"). CASE: A 34-year-old
      multigravida was referred to labor and delivery at 24 and weeks after ultrasound
      findings of a shortened cervix, multiple uterine synechiae, and multiple fetal
      anomalies. Two weeks after admission, she experienced preterm premature rupture
      of membranes with subsequent variable decelerations requiring delivery via
      classical cesarean. The fetal malformations were attributed to the multiple
      uterine synechiae caused by the previous endometrial ablation. CONCLUSION: This
      case illustrates the significant morbidity and mortality associated with a
      pregnancy complicated by uterine synechiae after an endometrial ablation.

PMID- 15863574
TI  - Vaginal mullerian cyst presenting as a cystocele.
AB  - BACKGROUND: Vaginal cysts occur rarely, are usually discovered incidentally on
      examination, and can cause a variety of symptoms. CASE: This article discusses a
      34-year-old para 2 female with a large anterior vaginal wall cyst that arose at
      20 weeks' gestation and was originally diagnosed as a cystocele. The unusual
      timing of its occurrence and the characteristics of the anterior vaginal wall
      prompted ancillary testing and reexamination. CONCLUSION: The timing of onset and
      general characteristics of prolapse as well as defecography and magnetic
      resonance imaging can be used to aid the gynecologist in diagnosing vaginal cysts
      instead of the more common condition of vaginal prolapse.

PMID- 15863575
TI  - Conservative management of extra-adrenal pheochromocytoma during pregnancy.
AB  - BACKGROUND: Extra-adrenal pheochromocytomas are catecholamine-secreting tumors
      that arise from chromaffin cells of the paraganglion sympathetic system. All of
      the previously reported cases have described surgical resection during the
      antepartum period. CASE: At 14 weeks of gestation, a multiparous patient was
      diagnosed with an extra-adrenal dopaminergic pheochromocytoma. A decision was
      made to delay surgical intervention until the postpartum period.
      Phenoxybenzamine, 10 mg per day, was subsequently started. At 35 + 2 weeks of
      gestation, the patient delivered a 2,600 g infant via an uncomplicated cesarean.
      Three weeks later, the extra-adrenal pheochromocytoma was removed, and she also
      underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and
      rectosigmoid resection with end-to-end colostomy. CONCLUSION: Conservative
      management of dopaminergic-secreting extra-adrenal pheochromocytomas can result
      in favorable maternal and fetal outcomes.

PMID- 15863576
TI  - Mucous membrane pemphigoid of the vulva.
AB  - BACKGROUND: Mucous membrane pemphigoid is a rare autoimmune blistering disease
      primarily affecting mucosal surfaces. Blistering and scarring may occur in the
      eyes, mouth, esophagus, larynx, and on the vulva. Scarring can result in severe
      structural changes to the vulva that may mimic the findings of other inflammatory
      dermatologic disorders of the vulva, including lichen sclerosus and lichen
      planus. CASE: A 58-year-old woman presented with vulvar erosions, esophagitis,
      and laryngeal blisters. The clinical picture and the histopathology of a vulvar
      biopsy were suggestive of erosive lichen planus. Direct immunofluorescence,
      however, revealed findings diagnostic of mucous membrane pemphigoid. CONCLUSION:
      This case illustrates the importance of examining extragenital mucosal surfaces
      of any woman presenting with vulvar lesions. In addition, it demonstrates the
      importance of vulvar biopsy and the usefulness of direct immunofluorescence to
      differentiate between conditions with similar clinical and histopathologic
      changes.

PMID- 15863577
TI  - A bicornuate uterus with a unilateral cornual adenomyosis.
AB  - BACKGROUND: Few reports have described adenomyosis in association with congenital
      uterine abnormalities. The authors present a case involving unilateral
      adenomyosis in a bicornuate uterus. CASE: A 41-year-old married gravida 1, para
      1, first became aware that she had a double uterus 14 years earlier at her first
      prenatal examination when the gestation was identified in the left uterine cavity
      because of intractable dysmenorrhea. The patient underwent laparoscopically
      assisted vaginal hysterectomy. Pathological examination confirmed that
      adenomyosis had affected only the left uterine myometrium. CONCLUSION: The right
      uterine cornua of a bicornuate uterus served as the control after a pregnancy in
      the left cornua. The subsequent development of adenomyosis in the left cornua
      lends weight to theories that suggest pregnancy or other acquired factors may be
      involved in the pathogenesis and development of adenomyosis.

PMID- 15863578
TI  - Suprapubic-vaginocutaneous fistula 18 years after a bladder-neck suspension.
AB  - BACKGROUND: Several complications are associated with healing after pelvic
      reconstructive surgery for stress urinary incontinence. These include infection,
      hemorrhage, erosion, and fistula formation. CASE: A 67-year-old woman presented
      with simultaneously draining vaginal and suprapubic sinuses. Examination revealed
      a vagino-abdominal fistula. Surgical excision found an abscess around synthetic
      material from a previous bladder-neck suspension. CONCLUSION: Unusual fistulation
      can occur remotely from anti-incontinence surgery, especially when graft
      materials are used.

PMID- 15863579
TI  - Pregnancy after gastric bypass surgery and internal hernia formation.
AB  - BACKGROUND: Gastric bypass is a surgical procedure that is increasingly performed
      in the United States to treat morbid obesity. Because of the changes associated
      with pregnancy, women with a history of gastric bypass surgery may be at an
      increased risk of gastrointestinal complications during the antepartum period, as
      demonstrated by these cases. CASES: The first patient presented at 12 weeks of
      gestation with abdominal pain. Computed tomography scan revealed rotation of the
      small bowel mesentery. In the operating room, a Petersen's internal hernia was
      observed. The second patient presented at 34 weeks of gestation with epigastric
      pain, nausea, and vomiting. An abdominal computed tomography scan suggested
      distention of the biliopancreatic limb, duodenum, and bypassed stomach. She
      underwent exploratory laparotomy with repair of an internal (mesenteric loop)
      hernia. CONCLUSION: As obstetricians, we should be aware of the potential for
      internal hernias in pregnant patients who have undergone bariatric surgery.

PMID- 15863580
TI  - Uterine sarcoidosis potentially associated with interferon-alpha use for chronic
      hepatitis C infection.
AB  - BACKGROUND: A regimen including interferon-alpha has become the standard of care
      in the treatment of chronic hepatitis C over the last decade. One rare adverse
      effect associated with the use of interferon-alpha is a granulomatous pulmonary
      reaction. CASE: A unique case of uterine sarcoidosis associated with the use of
      interferon-alpha for chronic hepatitis C infection is presented. CONCLUSION:
      Gynecologists should be aware of a potential association between interferon-alpha
      therapy and granulomatous reactions occurring not only in the lung but also in
      the female genital tract.

PMID- 15863581
TI  - An operative technique for conservative management of placenta accreta.
AB  - BACKGROUND: Control of bleeding is the goal of management for placenta accreta,
      which usually necessitates hysterectomy. A Committee Opinion of The American
      College of Obstetricians and Gynecologists (ACOG) has addressed the difficulties
      of conservative treatments. CASES: Placentas of 2 primiparous women with placenta
      accreta were removed operatively from their uteri. One woman underwent a low
      transverse cesarean delivery, and the other had delivered vaginally. In each
      case, the anterior uterine wall was incised vertically between the lower segment
      and fundus before manual removal. After eversion of the uterus, the placenta was
      successfully detached from the uterine wall after intramyometrial administration
      of oxytocin. CONCLUSION: A vertical incision in the anterior uterine wall and
      subsequent eversion of the uterus may aid in avoiding hysterectomy with placenta
      accreta.

PMID- 15863582
TI  - Anomalies associated with failed methotrexate and misoprostol termination.
AB  - BACKGROUND: Methotrexate and misoprostol are frequently used in combination for
      medical termination of pregnancy. Despite their frequent use, published
      information about low-dose exposures to these known teratogens is sparse and
      neonatal follow-up data are limited. We present neonatal outcomes in three
      infants from two different women who had failed medical terminations with
      methotrexate and misoprostol. CASES: A young gravida 1, para 0, presented with
      intrauterine pregnancy complicated by first-trimester exposure to oral
      methotrexate and vaginal misoprostol. Ultrasonography determined that the fetus
      had intrauterine growth restriction and ventriculomegaly. The infant had growth
      and developmental delays. A young gravida 4, para 3-0-0-3, also presented after
      first trimester exposure to methotrexate and misoprostol, and was found to have a
      twin gestation. The infants were noted to have multiple congenital anomalies,
      growth restriction, and developmental delay. CONCLUSION: Even single doses of
      methotrexate and misoprostol used in medical termination of pregnancy can be
      associated with multiple congenital anomalies.

PMID- 15863583
TI  - Benign vaginal villi noted at time of defibulation of female genital cutting.
AB  - BACKGROUND: Female genital cutting is a cultural practice in Africa and the
      Middle East. As more patients who have undergone this procedure are seen in the
      United States and undergo surgical revision of the scarred labia, new clinical
      findings will arise. CASE: At the time of surgical revision of female genital
      cutting, small clusters of villi were noted on the vaginal and labial mucosa of 3
      patients. Pathological examination revealed benign-appearing papillary
      structures. These villi completely resolved by the 6-week postoperative visit.
      CONCLUSION: Female genital cutting may lead to a vaginal environment that
      predisposes women to benign changes in the vaginal mucosa that resolve after the
      closed (infibulated) labia are surgically revised.

PMID- 15863584
TI  - Programming ovulation using estrogens for patients to time intercourse.
AB  - BACKGROUND: A woman wishing to conceive may be separated from her spouse at the
      time of ovulation. Moreover, some orthodox Jewish women have a unique problem
      when they are unable to initiate intercourse before ovulation. They are
      prohibited from participating in sexual relations from the start of menstruation
      until 7 days after the end of flow when they go to the ritual bath (mikveh).
      CASES: Two orthodox Jewish women who ovulated before restarting intercourse were
      treated with oral estrogens to delay ovulation. CONCLUSION: Women separated from
      their husbands at the time of ovulation and Jewish women who ovulate before
      ritual cleansing can effectively use oral estrogens to program ovulation.

PMID- 15863585
TI  - Temporary Erb-Duchenne palsy without shoulder dystocia or traction to the fetal
      head.
AB  - BACKGROUND: Although many retrospective studies report that brachial plexus
      palsies occur after vaginal delivery in the absence of recorded shoulder
      dystocia, there are no known prospective reports by a treating clinician (PubMed,
      English language only, 1952-June 2004, search terms: shoulder dystocia,
      nonshoulder dystocia, obstetric brachial plexus injury, Erb's palsy, Erb-Duchenne
      palsy, spontaneous vaginal delivery). CASE: A multiparous patient presented with
      a birth plan requesting that the baby be allowed to deliver on its own, without
      traction on the head and without suctioning. Although induced at term for
      elevated blood pressure, the otherwise healthy patient experienced a normal labor
      with a 30-minute second stage. At delivery, which was videotaped by the father,
      the fetal head presented over an intact perineum in a right-occiput-anterior
      position. Without traction, the anterior shoulder delivered spontaneously with
      the next contraction and Valsalva, followed by the posterior shoulder. The trunk
      followed routinely. The average-weight for gestational age neonate exhibited an
      Erb-Duchenne palsy of the right (posterior) arm that resolved on the fourth day
      of life. CONCLUSION: Temporary Erb-Duchenne palsy can occur in the posterior arm
      after normal labor and spontaneous delivery without shoulder dystocia or traction
      on the fetal head.

PMID- 15863586
TI  - Maternal death after second-trimester genetic amniocentesis.
AB  - BACKGROUND: We report a maternal death after a second-trimester amniocentesis.
      CASE: An uncomplicated amniocentesis was performed using sterile technique and
      ultrasound guidance. A refrigerated amniotic fluid specimen demonstrated negative
      leukocyte esterase activity, negative Gram stain for bacteria and white blood
      cells, and normal glucose and interleukin-6. The patient died from Escherichia
      coli sepsis and disseminated intravascular coagulation 40 hours after the
      amniocentesis. The autopsy showed normal- appearing needle entries into the skin
      and uterus without evidence of bowel adhesion or a needle track through the
      bowel. CONCLUSION: Genetic counselors and obstetric care providers should be
      aware of potential serious maternal morbidity and mortality that may occur
      subsequent to uncomplicated amniocentesis.

PMID- 15863588
TI  - Massive luteinized follicular cyst of pregnancy.
AB  - BACKGROUND: A large luteinized follicular cyst can rupture or twist during
      pregnancy. However, in the absence of those complications a simple ovarian cyst
      can often be managed conservatively, provided that sonographic evaluation of the
      cyst is benign. Rapid growth of a simple follicular cyst is rare but may
      occasionally complicate pregnancy. CASE: A 25-year-old primigravida had a simple
      appearing adnexal mass detected by sonogram early in pregnancy. She was followed
      with serial sonograms. Because of the clear sonolucent appearance of the mass and
      the patient's preference, a conservative management was elected. The cyst grew in
      size as her pregnancy progressed, became symptomatic, and necessitated surgical
      intervention. Cystectomy and cesarean delivery at 36+ weeks relieved the symptoms
      and achieved delivery of a healthy infant. CONCLUSION: Solitary luteinized
      follicular cysts of pregnancy have the potential to grow to a very large size and
      create complications related to their size alone. Conservative management of
      simple adnexal cysts in pregnancy, based on their sonographic appearance, can
      avoid risks of abdominal surgery in the second trimester of pregnancy, but in the
      third trimester, a large cyst can create significant complications requiring
      surgical intervention.

PMID- 15863587
TI  - Follicle stimulating hormone-secreting pituitary microadenoma with fluctuating
      levels of ovarian hyperstimulation.
AB  - BACKGROUND: Enlarged multicystic ovaries and an elevated estradiol (E2)
      concentration have been reported as characteristics of follicle stimulating
      hormone (FSH)-secreting adenomas in reproductive-aged women. The natural course
      of the hormone in relationship to the microadenoma and ovarian findings, however,
      remains largely unknown. CASE: A 40-year-old woman with enlarged multicystic
      ovaries was nonsurgically diagnosed with an FSH-producing pituitary microadenoma.
      During her subsequent 12-month follow-up, the serum concentration of E2, but not
      FSH, and the size of the multicystic ovaries fluctuated dramatically. Both the E2
      level and ovarian size were transiently normalized. CONCLUSION: Because of
      disease-related fluctuations, a reproductive-aged woman with an FSH-producing
      adenoma did not always present with laboratory values characteristic of ovarian
      hyperstimulation. This finding points out a possible pitfall in diagnosis and
      clinical management.

PMID- 15863589
TI  - Severe Graves' ophthalmopathy in pregnancy.
AB  - BACKGROUND: Thyroid ophthalmopathy is a rare extrathyroidal complication most
      commonly associated with Graves' disease. The disease course ranges from mild to
      severe, with severe cases resulting in major visual impairment and facial
      disfigurement. CASE: A 22-year-old primigravida developed severe thyroid
      ophthalmopathy during pregnancy, requiring high-dose steroids and surgical
      orbital wall decompression to restore visual acuity. CONCLUSION: Severe thyroid
      ophthalmopathy can occur in the euthyroid pregnant patient. Corticosteroid
      therapy and surgical intervention may be required during pregnancy in this
      clinical scenario.

PMID- 15863590
TI  - von Willebrand's disease diagnosed after menorrhagia worsened from levonorgestrel
      intrauterine system.
AB  - BACKGROUND: Adult females with menorrhagia may have unrecognized mild von
      Willebrand's disease. Most females with known von Willebrand's disease report
      menorrhagia. CASE: A 38-year-old healthy female desired contraception. She
      described heavy menses lasting 8 days since menarche. History included
      uncomplicated vaginal deliveries. Physical examination was normal. The
      levonorgestrel intrauterine system was placed. Her menorrhagia then worsened to
      14 successive days each month. Evaluation revealed mild von Willebrand's disease.
      At 19 months of follow-up, she retained her levonorgestrel intrauterine system
      and avoided pregnancy. Her menses slowly improved to spotting for 8 days each
      month. CONCLUSION: Von Willebrand's disease is a likely cause of menorrhagia that
      goes unrecognized as well as a potential cause for "failed" conservative
      treatment for menorrhagia. Understanding the cause of menorrhagia is an important
      aspect of evaluating this common symptom.

PMID- 15863591
TI  - Prenatal diagnosis of 13q-syndrome in a fetus with Dandy-Walker malformation.
AB  - BACKGROUND: Partial deletion of the long arm of the chromosome 13 is a rare
      chromosomal aberration and may present with microcephaly, colobomata,
      microphthalmia, distal limb and digital anomalies, cardiac defects, brain and
      urogenital malformations, anal atresia and growth restriction. CASE: We report
      such a case in 25th week of gestation referred for sonographic examination which
      revealed growth restriction, microcephaly, Dandy-Walker malformation, right
      microphthalmia, micrognathia, marked nuchal edema, four fingers-oligodactyly in
      feet and in hands with thumb aplasia and ambiguous genitalia. Chromosome analysis
      identified chromosome 13q deletion [46 XY del (13) (13q31.2/q32.1 --> qter)].
      Postmortem examination confirmed prenatal findings and showed aniridia, low-set
      ears, cryptorchidism, and anal atresia. CONCLUSION: Detection of Dandy-Walker
      malformation, microphthalmia, oligodactyly with thumb aplasia and growth
      restriction during prenatal ultrasonography should be a reminder of deletion of
      chromosome 13q and warrant cytogenetic analysis.

PMID- 15863592
TI  - Symphyseal separation.
AB  - BACKGROUND: Separation of the pubic symphysis up to 1 cm during pregnancy and
      delivery occurs frequently. This report presents a woman who experienced a large
      symphyseal separation. CASE: Following delivery, a 35-year-old primipara
      complained of hip and groin pain associated with leg movement. An anterior
      posterior pelvic X-ray showed a pubic separation of 9.5 cm and a 3-5 mm widening
      of the sacroiliac joints. She was treated with a pelvic binder, walker, and
      physical therapy. The diastasis has since undergone progressive reduction.
      CONCLUSION: Separation of the pubic symphysis during pregnancy and delivery is
      normal. However, a large separation is a potential complication requiring
      treatment and follow-up. Conservative management including analgesia, rest, and a
      pelvic binder is a reasonable method of management.

PMID- 15863593
TI  - Renal artery stenosis due to fibromuscular dysplasia in an 18-week pregnant
      woman.
AB  - BACKGROUND: Hypertension is a frequent medical complication of pregnancy.
      Renovascular hypertension is present in 5-10% of cases of severe hypertension
      during pregnancy. CASE: In this report we describe a 36-year-old woman with
      severe hypertension caused by bilateral renal artery stenosis due to
      fibromuscular dysplasia. Guided by the patient's ultrasound findings, only 1 side
      was treated with angioplasty. Continued labile blood pressure resulted in
      arteriography of the contralateral renal artery, which confirmed renal artery
      stenosis was present on the other side. CONCLUSION: Clinicians should maintain a
      high index of suspicion for renovascular hypertension in pregnancy when drug
      resistance is present. Because the potential for false-negative results with
      noninvasive testing for renal artery stenosis is present, if clinical suspicion
      is high, one should consider using invasive testing.

PMID- 15863594
TI  - Umbilical cord stricture: a cause of recurrent fetal death.
AB  - BACKGROUND: Umbilical cord stricture is a recognized cause of fetal demise, but
      the exact etiology remains unknown. The risk of recurrence has generally been
      thought to be low. CASE: Three of 4 fetuses of a single patient died between 28
      and 30 weeks of gestation; all were found to have stricture of the umbilical cord
      at the fetal insertion. Her one surviving infant was delivered emergently at 25
      weeks. All infants were growth restricted but had no anatomic abnormalities.
      CONCLUSION: Umbilical cord stricture was diagnosed as the cause of all 3 fetal
      deaths. Patients with a demise attributed to umbilical cord stricture should be
      counseled that the risk of recurrent cord stricture is undetermined.

PMID- 15863595
TI  - Symptomatic cecal perforation by an intrauterine device with appendectomy
      removal.
AB  - BACKGROUND: The intrauterine device is the most used contraceptive in the world,
      but it is not without risk of perforation of intra-abdominal organs. We report a
      perforation of the cecum and removal via appendectomy. CASE: A 23-year-old woman
      developed chronic abdominal pain after insertion of an intrauterine device 8
      weeks postpartum. At laparoscopy, the device was found in the cecum and removed
      via appendectomy. CONCLUSION: Perforation is more common in the immediate
      postpartum state. An alternate method of removal via appendectomy proved useful.

PMID- 15863596
TI  - Herpes simplex virus 2-associated hemophagocytic lymphohistiocytosis in a
      pregnant patient.
AB  - BACKGROUND: Uncontrolled phagocytosis of normal hemopoietic cells by activated
      histiocytes in bone marrow is collectively referred to as hemophagocytic
      lymphohistiocytosis. CASE: We present a case of hemophagocytic
      lymphohistiocytosis associated with herpes simplex virus-2 infection in the
      second trimester. Cytopenia, elevated C-reactive protein, ferritin, soluble
      interleukin-2 receptor, and interleukin-6 with high-grade fever were observed
      following genital herpes infection, and the existence of hemophagocytes in bone
      marrow confirmed the diagnosis of hemophagocytic lymphohistiocytosis.
      Corticosteroid therapy failed to arrest the hemophagocytic process, whereas
      cyclosporin A was effective. The patient delivered a healthy infant after
      remission and has not experienced exacerbation. CONCLUSION: It is often important
      to take into consideration hemophagocytic lymphohistiocytosis when encountering
      cytopenia with high-grade fever. Cyclosporin A was a safe and available strategy
      for this corticosteroid-resistant case.

PMID- 15863597
TI  - Postpartum "psychosis" in mild argininosuccinate synthetase deficiency.
AB  - BACKGROUND: Urea cycle disorders are relatively rare but well-established causes
      of postpartum coma and death. Such clinical presentations have been reported
      previously in ornithine transcarbamylase and carbamyl phosphate synthetase
      deficiencies. CASE: We describe a woman, without prior symptoms of metabolic
      disease, who presented with hyperammonemia and psychiatric symptoms in the
      postpartum period. Initial diagnoses included acute fatty liver of pregnancy and
      postpartum psychosis. She was later found to have argininosuccinate synthetase
      deficiency after further metabolic investigations. Rare heterozygous mutations in
      the argininosuccinate synthetase gene were identified. CONCLUSION: Urea cycle
      disorders may present initially with postpartum psychiatric symptoms and may
      represent an underrecognized cause of "postpartum psychosis." We recommend
      obtaining metabolic studies in women with neurologic or severe psychiatric
      symptoms in the postpartum period.

PMID- 15863598
TI  - Conservative management of placenta previa percreta in a Jehovah's Witness.
AB  - BACKGROUND: Hemorrhage is a serious threat with placenta accreta, often requiring
      aggressive operative intervention by hysterectomy and resuscitative measures with
      large-volume blood replacement to ensure survival. Refusal to accept transfusion
      makes management especially difficult. CASE: We report a Jehovah's Witness
      patient who had 9 previous cesarean deliveries and presented with anemia and
      placenta previa percreta invading the bladder wall. Management objectives were to
      enhance the patient's status, using erythropoietin and autologous transfusion,
      and to minimize the chance of hemorrhage by prophylactic uterine artery
      embolization. The placenta was left in situ after the delivery with no untoward
      consequences. Methotrexate was held in readiness, but was not required as
      adjuvant therapy. CONCLUSION: Effective care of such patients requires close
      collaborative team effort and advanced planning to ensure a good outcome.

PMID- 15863599
TI  - Treatment of metastatic gestational choriocarcinoma with oral methotrexate in a
      combat environment.
AB  - BACKGROUND: Gestational trophoblastic neoplasia (GTN) is a rare neoplastic
      complication of pregnancy. This disease can be successfully treated with
      parenteral intravenous or intramuscular chemotherapy. We present a case of
      metastatic gestational choriocarcinoma following a term pregnancy that was
      treated successfully with oral methotrexate therapy. CASE: A 25-year-old, G4 P4,
      native Afghani with a history of irregular menses since the birth of her son 6
      months ago received a physical examination that was within normal limits. Pelvic
      examination revealed minimal blood in the vault and slight bleeding from a closed
      cervical os. The uterus was slightly enlarged, 5 weeks in size, and without any
      adnexal masses. Laboratory evaluation was significant for a positive urine and
      serum beta-HCG. Pelvic ultrasound examination revealed a 5-cm uterus with a 2-cm
      endometrial stripe. Chest radiograph revealed multiple bilateral ill-defined
      pulmonary nodules confirmed by computerized tomography. The patient underwent
      dilation and curettage productive of a moderate amount of tissue. The patient
      continued to have positive serum beta-HCGs and was given the presumptive
      diagnosis of FIGO stage III gestational choriocarcinoma. Because of the lack of
      intravenous chemotherapeutic agents, the patient was begun on methotrexate 0.40
      mg/kg orally on days 1-5, with 9 days off. The patient completed one course of
      chemotherapy, followed by an interval total abdominal hysterectomy with bilateral
      salpingo-oophorectomy. The patient had a complete response to therapy and was
      treated with oral methotrexate for 2 courses after a negative serum beta-HCG. The
      patient tolerated the chemotherapy without any complication. CONCLUSION:
      Methotrexate is routinely used in a parenteral intramuscular fashion for the
      treatment of gestational choriocarcinoma. Physicians should be aware that, in
      very limited situations, oral methotrexate in combination with hysterectomy still
      could offer a patient successful treatment for stage III GTN.

PMID- 15863600
TI  - Human immunodeficiency virus, pregnancy, and Stevens-Johnson syndrome.
AB  - BACKGROUND: Stevens-Johnson syndrome and toxic epidermal necrolysis are life
      threatening dermatologic disorders that are more common in the setting of a
      compromised immune system. We present the case of a pregnant patient with known
      human immunodeficiency virus (HIV) infection who presented with Stevens-Johnson
      syndrome after treatment with antibiotics for a urinary tract infection. CASE: A
      young woman at 33 4/7 weeks of gestation with known HIV infection presented to
      the emergency room with a chief complaint of rash, fever, blisters, and lower
      abdominal pain. Her symptoms were present for 2 days after ingestion of
      nitrofurantoin, prescribed for a urinary tract infection. She was diagnosed with
      preterm labor and possibly Stevens-Johnson syndrome. Due to active labor, HIV,
      and vaginal stenosis, a primary cesarean was performed. A skin biopsy performed
      at the time of admission confirmed the diagnosis of a drug-induced dermatosis
      (erythema multiforme), evidenced by subepidermal bullae, hemorrhage, and
      acantolated, dyskeratotic eosinophilic cells. CONCLUSION: Stevens-Johnson
      syndrome and toxic epidermal necrolysis represent a spectrum of disease that has
      been long associated with multiple drugs, recently including many antiretroviral
      medications. It also seems that the incidence of these conditions is increased in
      immunocompromised patients. We speculate that the combination of HIV and
      pregnancy in addition to antibiotic treatment, such as with nitrofurantoin, may
      induce Stevens-Johnson syndrome in patients with severely altered immune systems.

PMID- 15863601
TI  - Transperineal resection of a retroperitoneal liposarcoma presenting as a perineal
      mass.
AB  - BACKGROUND: Liposarcomas can present as giant liposarcomas in the retroperitoneal
      position. CASE: A healthy woman presented with a large recurrent proboscis-type
      mass at the left gluteus and underwent a transperineal resection of the mass. The
      patient tolerated the procedure well and was discharged after a short
      hospitalization. CONCLUSION: Once invasion into adjacent structures has been
      ruled out, a transperineal resection of giant retroperitoneal liposarcomas can be
      performed.

PMID- 15863602
TI  - Neonatal group B streptococcus sepsis after negative screen in a patient taking
      oral antibiotics.
AB  - BACKGROUND: Group B streptococcus (GBS) is a leading cause of serious neonatal
      infection. Neonatal morbidity and mortality can be reduced by appropriate
      prenatal screening and intrapartum chemoprophylaxis. CASE: A 20-year-old
      primigravida was treated with oral antibiotics at 35 weeks for a recurrent
      urinary tract infection. Her GBS screen following the antibiotic treatment showed
      a negative culture. The patient, therefore, did not receive intravenous
      antibiotics during her induction of labor for mild preeclampsia. The infant
      developed early onset neonatal GBS pneumonia and sepsis. CONCLUSION: Oral
      antibiotics can cause a temporary negative culture in a GBS-colonized patient.
      Relying on a negative culture for management may not be appropriate in a patient
      treated with oral antibiotics. Additional studies are necessary to elucidate the
      effects of oral antibiotics on GBS.

PMID- 15863603
TI  - Pruritic urticarial papules and plaques of pregnancy with unusual and extensive
      palmoplantar involvement.
AB  - BACKGROUND: Pruritic urticarial papules and plaques of pregnancy (PUPPP) is a
      specific dermatosis of pregnancy common to primigravid women in the third
      trimester. The rash usually begins on the lower abdomen within striae and spreads
      to the proximal extremities. Involvement of face, palms, and soles is unusual.
      Although intensely pruritic, the fetus is unaffected, and the condition does not
      usually recur. It can be difficult to distinguish PUPPP from pemphigoid
      gestationis, an autoimmune bullous disorder with potential fetal consequences
      that may recur with subsequent pregnancy, menses, or hormonal therapy. CASE: A
      young secundagravida at 36 weeks of gestation with monochorionic twins presented
      with a 3-week history of a pruritic papular eruption that began on the abdomen
      and spread to the extremities. She had extensive involvement of the distal
      extremities, including the palmoplantar surfaces, with small vesicles of 2-4 mm
      on acral skin. Because of her unusual presentation, she was thought initially to
      have pemphigoid gestationis. Subsequent dermatological evaluation and a biopsy
      confirmed the diagnosis of PUPPP. Shortly after admission she delivered 2 healthy
      male infants, and her rash cleared with conservative management. CONCLUSION:
      Pruritic urticarial papules and plaques of pregnancy often, but not always,
      spares the face, palms, and soles. Small vesicles can occur in PUPPP, but
      formation of true bullae is not observed. Careful dermatological examination and
      cutaneous biopsy can assist in differentiating PUPPP from pemphigoid gestationis,
      which is essential for treatment and prognosis.

PMID- 15863604
TI  - Recurrent mature cystic ovarian teratoma in adolescence: atypical case of the
      growing teratoma syndrome.
AB  - BACKGROUND: A primary mature cystic ovarian teratoma was diagnosed in an
      adolescent female. She was followed up after initial exploration with computed
      tomography, pelvic ultrasonography, and serum tumor markers. Recurrent tumor,
      consisting solely of mature teratomatous elements, was confirmed with 2
      subsequent laparotomies. CASE: This is a report of the growing teratoma syndrome
      in a young woman with a primary diagnosis of a mature cystic ovarian teratoma not
      treated with adjuvant chemotherapy. CONCLUSION: The growing teratoma syndrome is
      an uncommon condition. Surgical resection of recurrent lesions is necessary to
      reduce potential complications of abdominopelvic organ compression and
      obstruction and to evaluate for the presence of malignant degeneration.

PMID- 15863605
TI  - Postoperative ascites associated with intraperitoneal antiseptic lavage.
AB  - BACKGROUND: Peritonitis is the established term for infective inflammation of the
      peritoneum, whereas serositis generally refers to aseptic inflammation of a
      serous cavity, including the peritoneum. Serositis may be metabolic, viral,
      autoimmune, drug induced, genetic, allergic or granulomatous, or due to chemical
      antiseptics. CASES: In our gynecological department, 4 patients had peritonitis
      and ascites after laparotomy. CONCLUSION: Based on the investigation, we think
      that the solution used for peritoneal lavage (0.1% octenidine dihydrochloride and
      2% phenoxyethanol) played a role in the tissue toxicity that caused chemical
      serositis with effusion.

PMID- 15863606
TI  - The use of acellular dermal graft for vulvovaginal reconstruction in a patient
      with lichen planus.
AB  - BACKGROUND: Vulvovaginal lichen planus is an inflammatory dermatosis that can
      progress to an erosive form with scarring of the vulva, resorption of the labia
      minora, vaginal synechiae, and vaginal obliteration secondary to desquamative
      vaginitis. Traditionally, conservative medical therapy has consisted of topical
      corticosteroids and immunosuppressants. CASE: A 61-year-old woman with a history
      of refractory erosive vulvovaginal lichen planus presented with complete
      obliteration of the vaginal vault. The patient failed both medical and
      conservative surgical management and desired definitive management. After
      performing a skinning vulvectomy and simple vaginectomy, acellular dermal graft
      was used for grafting the vulva and creating a neovagina. CONCLUSION: Acellular
      dermal graft is a suitable graft material for vulvar and vaginal reconstruction
      in select patients, and it avoids the postoperative pain associated with graft
      harvest sites.

PMID- 15863607
TI  - Diagnosis of liver infarction postpartum.
AB  - BACKGROUND: Patients with antiphospholipid syndrome (APS) have increased risks of
      developing thromboembolism, and the risk maybe amplified by the hypercoagulable
      state associated with pregnancy. CASE: A patient presented with severe chest
      pain, mild pyrexia associated with elevated serum transaminases, and marked
      neutrophilia after vaginal delivery. Liver infarction was diagnosed by spiral
      computer tomography and treated successfully with anticoagulation. CONCLUSION:
      Liver infarction is a possible diagnosis in a patient with antiphospholipid
      syndrome who presents with chest or abdominal pain in the postpartum period.

PMID- 15863608
TI  - The case of the missing "Prince Albert".
AB  - BACKGROUND: Body piercing is increasing and so are its complications. We describe
      a case in which the female partner of an individual who had penile piercing was
      affected. CASE: A young female presented to the emergency department with the
      possibility of a lost/missing foreign body in the vagina. Her partner had had a
      "Prince Albert" type of penile piercing, which was found to be missing after
      sexual intercourse. Prince Albert penile piercing is a metallic bead, which is
      anchored to the urethral opening. On clinical examination, the bead was not found
      in the vagina but was seen on pelvic X-ray. A thorough sexual history resolved
      the mystery of the missing Prince Albert. CONCLUSION: Our case suggests that the
      gynecologist should be aware of the practice of genital piercing and stresses the
      importance of proper sexual history taking.

PMID- 15863609
TI  - Rupture of fetal ductus arteriosus aneurysm.
AB  - BACKGROUND: Ductus arteriosus aneurysm is a rare fetal disorder. CASE: A 35-year
      old primigravida had an uneventful antenatal course. Ultrasound examination at 30
      weeks of gestation revealed hydramnios. The fetal ductus arteriosus became
      saccular and dilated with turbulent flow and diameter of 2.5 cm. It was located
      at the left upper thorax, just distal to the pulmonic valve and extended to the
      thoracic aorta. A ductus arteriosus aneurysm was diagnosed prenatally. Five days
      after diagnosis, preterm labor occurred, and dexamethasone and terbutaline were
      administered. Six hours after initiation of terbutaline, the fetal heart rate
      suddenly dropped to 90 beats per minute (bpm). A bedside ultrasound examination
      performed immediately showed profound bradycardia. The aneurysm became a
      heterogeneous hypoechoic mass with no pulsation, and the fetal heart rate
      suddenly disappeared. CONCLUSION: Ductus arteriosus aneurysm can be diagnosed
      prenatally, and terbutaline or dexamethasone may be associated with a risk for
      rupture.

PMID- 15863610
TI  - Malignant mixed mullerian tumor of the uterus in a patient taking raloxifene.
AB  - BACKGROUND: Uterine malignant mixed mesodermal tumor is a rare variant of uterine
      cancer. Data suggest that tamoxifen is involved in the pathogenesis. We report a
      case of a women in whom a malignant mixed mesodermal tumor was diagnosed while
      she was taking raloxifene, which is also a selective estrogen receptor modulator.
      CASE: A malignant mixed mesodermal tumor was diagnosed in a 64-year-old woman
      with a bicornuate uterus while she was taking raloxifene for osteoporosis
      prevention. Diagnosis had been delayed secondary to sampling of the other uterine
      horn. CONCLUSION: There may be an association between raloxifene and the
      development of malignant mixed mesodermal tumor. Special attention should be paid
      when attempting to sample the endometrium in patients with mullerian
      abnormalities.

PMID- 15863611
TI  - Enhanced dihydroflavonol-4-reductase activity and NAD homeostasis leading to cell
      death tolerance in transgenic rice.
AB  - The maize Hm1 gene encoding the NADPH-dependent HC-toxin reductase is capable of
      detoxifying HC-toxin of fungus Cochliobolus carbonum. Here, we conducted the
      metabolic and biochemical analysis in transgenic rice plants overexpressing an HC
      toxin reductase-like gene in rice (YK1 gene). Methods employing NADPH oxidation
      and capillary electrophoresis mass spectrometry analysis confirmed that YK1
      possessed dihydroflavonol-4-reductase activity in vitro and in vivo. The
      overexpression of YK1 in both suspension-cultured cells and rice plants increased
      NAD(H) and NADP(H) levels by causing an increase in NAD synthetase and NAD kinase
      activities. Activity changes in enzymes that require NAD(P) as coenzymes were
      also noted in rice cells ectopically expressing YK1, where the cell death caused
      by hydrogen peroxide and bacterial disease was down-regulated. Thus, a strategy
      was proposed that the combination of dihydroflavonol-4-reductase activity and the
      elevated level of NAD(P)H pool may confer the prevention of induced cell death in
      planta.

PMID- 15863612
TI  - Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.
AB  - Timothy syndrome (TS) is a multisystem disorder that causes syncope and sudden
      death from cardiac arrhythmias. Prominent features include congenital heart
      disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities,
      and autism. All TS individuals have syndactyly (webbing of fingers and toes). We
      discovered that TS resulted from a recurrent, de novo cardiac L-type calcium
      channel (CaV1.2) mutation, G406R. G406 is located in alternatively spliced exon
      8A, encoding transmembrane segment S6 of domain I. Here, we describe two
      individuals with a severe variant of TS (TS2). Neither child had syndactyly. Both
      individuals had extreme prolongation of the QT interval on electrocardiogram,
      with a QT interval corrected for heart rate ranging from 620 to 730 ms, causing
      multiple arrhythmias and sudden death. One individual had severe mental
      retardation and nemaline rod skeletal myopathy. We identified de novo missense
      mutations in exon 8 of CaV1.2 in both individuals. One was an analogous mutation
      to that found in exon 8A in classic TS, G406R. The other mutation was G402S. Exon
      8 encodes the same region as exon 8A, and the two are mutually exclusive. The
      spliced form of CaV1.2 containing exon 8 is highly expressed in heart and brain,
      accounting for approximately 80% of CaV1.2 mRNAs. G406R and G402S cause reduced
      channel inactivation, resulting in maintained depolarizing L-type calcium
      currents. Computer modeling showed prolongation of cardiomyocyte action
      potentials and delayed afterdepolarizations, factors that increase risk of
      arrhythmia. These data indicate that gain-of-function mutations of CaV1.2 exons 8
      and 8A cause distinct forms of TS.

PMID- 15863613
TI  - Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to
      the hypozincemia of the acute-phase response.
AB  - Infection and inflammation produce systemic responses that include hypozincemia
      and hypoferremia. The latter involves regulation of the iron transporter
      ferroportin 1 by hepcidin. The mechanism of reduced plasma zinc is not known.
      Transcripts of the two zinc transporter gene families (ZnT and Zip) were screened
      for regulation in mouse liver after turpentine-induced inflammation and LPS
      administration. Zip14 mRNA was the transporter transcript most up-regulated by
      inflammation and LPS. IL-6 knockout (IL-6(-/-)) mice did not exhibit either
      hypozincemia or the induction of Zip14 with turpentine inflammation. However, in
      IL-6(-/-) mice, LPS produced a milder hypozincemic response but no Zip14
      induction. Northern analysis showed Zip14 up-regulation was specific for the
      liver, with one major transcript. Immunohistochemistry, using an antibody to an
      extracellular Zip14 epitope, showed both LPS and turpentine increased abundance
      of Zip14 at the plasma membrane of hepatocytes. IL-6 produced increased
      expression of Zip14 in primary hepatocytes cultures and localization of the
      protein to the plasma membrane. Transfection of mZip14 cDNA into human embryonic
      kidney cells increased zinc uptake as measured by both a fluorescent probe for
      free Zn(2+) and (65)Zn accumulation, as well as by metallothionein mRNA
      induction, all indicating that Zip14 functions as a zinc importer. Zip14 was
      localized in plasma membrane of the transfected cells. These in vivo and in vitro
      experiments demonstrate that Zip14 expression is up-regulated through IL-6, and
      that this zinc transporter most likely plays a major role in the mechanism
      responsible for hypozincemia that accompanies the acute-phase response to
      inflammation and infection.

PMID- 15863614
TI  - Origin of the long-range attraction between surfactant-coated surfaces.
AB  - We compare the "long-range hydrophobic forces" measured (i) in the "symmetric"
      system between two mica surfaces that had been rendered hydrophobic by the
      adsorption of a double-chained cationic surfactant, and (ii) between one such
      hydrophobic surface and a hydrophilic surface of bare mica ("asymmetric" case).
      In both cases, the forces were purely attractive, stronger than van der Waals,
      and of long-range, as previously reported, with those of the asymmetric,
      hydrophobic-hydrophilic system being even stronger and of longer range. Atomic
      force microscopy images of these surfaces show that the monolayers transform into
      patchy bilayers when the surfaces are immersed in water, and that the resulting
      surfaces contain large micrometer-sized regions of positive charges (bilayer) and
      negative charges (bare mica) while remaining overall neutral. The natural
      alignment of oppositely charged domains as two such surfaces approach would
      result in a long-range electrostatic attraction in water, but the short-range,
      "truly hydrophobic" interaction is not explained by these results.

PMID- 15863615
TI  - Discovery of a unique Ig heavy-chain isotype (IgT) in rainbow trout: Implications
      for a distinctive B cell developmental pathway in teleost fish.
AB  - During the analysis of Ig superfamily members within the available rainbow trout
      (Oncorhynchus mykiss) EST gene index, we identified a unique Ig heavy-chain (IgH)
      isotype. cDNAs encoding this isotype are composed of a typical IgH leader
      sequence and a VDJ rearranged segment followed by four Ig superfamily C-1 domains
      represented as either membrane-bound or secretory versions. Because teleost fish
      were previously thought to encode and express only two IgH isotypes (IgM and IgD)
      for their humoral immune repertoire, we isolated all three cDNA isotypes from a
      single homozygous trout (OSU-142) to confirm that all three are indeed
      independent isotypes. Bioinformatic and phylogenetic analysis indicates that this
      previously undescribed divergent isotype is restricted to bony fish, thus we have
      named this isotype "IgT" (tau) for teleost fish. Genomic sequence analysis of an
      OSU-142 bacterial artificial chromosome (BAC) clone positive for all three IgH
      isotypes revealed that IgT utilizes the standard rainbow trout V(H) families, but
      surprisingly, the IgT isotype possesses its own exclusive set of D(H) and J(H)
      elements for the generation of diversity. The IgT D and J segments and tau
      constant (C) region genes are located upstream of the D and J elements for IgM,
      representing a genomic IgH architecture that has not been observed in any other
      vertebrate class. All three isotypes are primarily expressed in the spleen and
      pronephros (bone marrow equivalent), and ontogenically, expression of IgT is
      present 4 d before hatching in developing embryos.

PMID- 15863616
TI  - Structural dynamics of the lac repressor-DNA complex revealed by a multiscale
      simulation.
AB  - A multiscale simulation of a complex between the lac repressor protein (LacI) and
      a 107-bp-long DNA segment is reported. The complex between the repressor and two
      operator DNA segments is described by all-atom molecular dynamics; the size of
      the simulated system comprises either 226,000 or 314,000 atoms. The DNA loop
      connecting the operators is modeled as a continuous elastic ribbon, described
      mathematically by the nonlinear Kirchhoff differential equations with boundary
      conditions obtained from the coordinates of the terminal base pairs of each
      operator. The forces stemming from the looped DNA are included in the molecular
      dynamics simulations; the loop structure and the forces are continuously
      recomputed because the protein motions during the simulations shift the operators
      and the presumed termini of the loop. The simulations reveal the structural
      dynamics of the LacI-DNA complex in unprecedented detail. The multiple domains of
      LacI exhibit remarkable structural stability during the simulation, moving much
      like rigid bodies. LacI is shown to absorb the strain from the looped DNA mainly
      through its mobile DNA-binding head groups. Even with large fluctuating forces
      applied, the head groups tilt strongly and keep their grip on the operator DNA,
      while the remainder of the protein retains its V-shaped structure. A simulated
      opening of the cleft of LacI by 500-pN forces revealed the interactions
      responsible for locking LacI in the V-conformation.

PMID- 15863617
TI  - A unified assembly mode revealed by the structures of tetrameric L27 domain
      complexes formed by mLin-2/mLin-7 and Patj/Pals1 scaffold proteins.
AB  - Initially identified in Caenorhabditis elegans Lin-2 and Lin-7, L27 domain is a
      protein-protein interaction domain capable of organizing scaffold proteins into
      supramolecular assemblies by formation of heteromeric L27 domain complexes. L27
      domain-mediated protein assemblies have been shown to play essential roles in
      cellular processes including asymmetric cell division, establishment and
      maintenance of cell polarity, and clustering of receptors and ion channels. The
      structural basis of L27 domain heteromeric complex assembly is controversial. We
      determined the high-resolution solution structure of the prototype L27 domain
      complex formed by mLin-2 and mLin-7 as well as the solution structure of the L27
      domain complex formed by Patj and Pals1. The structures suggest that a tetrameric
      structure composed of two units of heterodimer is a general assembly mode for
      cognate pairs of L27 domains. Structural analysis of the L27 domain complex
      structures further showed that the central four-helix bundles mediating tetramer
      assembly are highly distinct between different pairs of L27 domain complexes.
      Biochemical studies revealed that the C-terminal alpha-helix responsible for the
      formation of the central helix bundle is a critical specificity determinant for
      each L27 domain in choosing its binding partner. Our results provide a unified
      picture for L27 domain-mediated protein-protein interactions.

PMID- 15863618
TI  - Structural mechanism of the recovery stroke in the myosin molecular motor.
AB  - The power stroke pulling myosin along actin filaments during muscle contraction
      is achieved by a large rotation ( approximately 60 degrees ) of the myosin lever
      arm after ATP hydrolysis. Upon binding the next ATP, myosin dissociates from
      actin, but its ATPase site is still partially open and catalytically off. Myosin
      must then close and activate its ATPase site while returning the lever arm for
      the next power stroke. A mechanism for this coupling between the ATPase site and
      the distant lever arm is determined here by generating a continuous series of
      optimized intermediates between the crystallographic end-states of the recovery
      stroke. This yields a detailed structural model for communication between the
      catalytic and the force-generating regions that is consistent with experimental
      observations. The coupling is achieved by an amplifying cascade of conformational
      changes along the relay helix lying between the ATPase and the domain carrying
      the lever arm.

PMID- 15863619
TI  - Caspase inhibition reduces tubular apoptosis and proliferation and slows disease
      progression in polycystic kidney disease.
AB  - We have previously demonstrated an increase in proapoptotic caspase-3 in the
      kidney of Han:SPRD rats with polycystic kidney disease (PKD). The aim of the
      present study was to determine the effect of caspase inhibition on tubular cell
      apoptosis and proliferation, cyst formation, and renal failure in the Han:SPRD
      rat model of PKD. Heterozygous (Cy/+) and littermate control (+/+) male rats were
      weaned at 3 weeks of age and then treated with the caspase inhibitor IDN-8050 (10
      mg/kg per day) by means of an Alzet (Palo Alto, CA) minipump or vehicle
      [polyethylene glycol (PEG 300)] for 5 weeks. The two-kidney/total body weight
      ratio more than doubled in Cy/+ rats compared with +/+ rats. IDN-8050
      significantly reduced the kidney enlargement by 44% and the cyst volume density
      by 29% in Cy/+ rats. Cy/+ rats with PKD have kidney failure as indicated by a
      significant increase in blood urea nitrogen. IDN-8050 significantly reduced the
      increase in blood urea nitrogen in the Cy/+ rats. The number of proliferating
      cell nuclear antigen-positive tubular cells and apoptotic tubular cells in non
      cystic and cystic tubules was significantly reduced in IDN-8050-treated Cy/+ rats
      compared with vehicle-treated Cy/+ rats. On immunoblot, the active form of
      caspase-3 (20 kDa) was significantly decreased in IDN-8050-treated Cy/+ rats
      compared with vehicle-treated Cy/+ rats. In summary, in a rat model of PKD,
      caspase inhibition with IDN-8050 (i) decreases apoptosis and proliferation in
      cystic and noncystic tubules; (ii) inhibits renal enlargement and cystogenesis,
      and (iii) attenuates the loss of kidney function.

PMID- 15863621
TI  - Finding transition states for crystalline solid-solid phase transformations.
AB  - We present a method to identify transition states and minimum energy paths for
      martensitic solid-solid phase transformations, thereby allowing quantification of
      the activation energies of such transformations. Our approach is a generalization
      of a previous method for identifying transition states for chemical reactions,
      namely the climbing image-nudged elastic band algorithm, where here the global
      deformation of the crystalline lattice (volume and shape fluctuations) becomes
      the reaction coordinate instead of atomic motion. We also introduce an analogue
      to the Born-Oppenheimer approximation that allows a decoupling of nuclear motion
      and lattice deformation, where the nuclear positions along the path are
      determined variationally according to current deformation state. We then apply
      this technique to characterize the energetics of elemental lithium phase
      transformations as a function of applied pressure, where we see a validation of
      the Born-Oppenheimer-like approximation, small energy barriers (expected for
      martensitic transformations), and a pronounced pressure dependence of various
      properties characterizing the phase transitions.

PMID- 15863620
TI  - Computer simulations of protein functions: searching for the molecular origin of
      the replication fidelity of DNA polymerases.
AB  - The use of computers to simulate the functions of complex biological
      macromolecules is essential to achieve a microscopic description of biological
      processes and to model and interpret experimental data. Here we apply theoretical
      computational approaches to investigate the fidelity of T7 DNA polymerase,
      divided into discrete steps that include contributions from substrate binding,
      pK(a) shifts, and rate constants for the PO bond-breaking and bond-making
      processes. We begin by defining the discrimination between right and wrong
      nucleotides in terms of the free energy landscape for the dNMP incorporation
      reaction. We then use the linear response approximation and the empirical valence
      bond methods to obtain converging results for the contribution of the binding and
      chemical steps to the overall fidelity. These approaches are successful in
      reproducing general trends in the observed polymerase incorporation fidelity. The
      calculations demonstrate the potential for further integration of theoretical and
      experimental studies to analyze high- and low-fidelity DNA polymerases.

PMID- 15863622
TI  - Perspective on the reactions between F- and CH3CH2F: the free energy landscape of
      the E2 and SN2 reaction channels.
AB  - Recently, we computed the 3D free energy surface of the base-induced elimination
      reaction between F(-) and CH(3)CH(2)F by using a powerful technique within Car
      Parrinello molecular dynamics simulation. Here, the set of three order parameters
      is expanded to six, which allows the study of the competing elimination and
      substitution reactions simultaneously. The power of the method is exemplified by
      the exploration of the six-dimensional free energy landscape, sampling, and
      mapping out the eight stable states as well as the connecting bottlenecks. The
      free energy profile and barrier along the E2 and S(N)2 reaction channels are
      refined by using umbrella sampling. The two mechanisms do not share a common "E2C
      like" transition state. Comparison with the zero temperature profiles shows a
      particularly significant entropy contribution to the S(N)2 channel.

PMID- 15863624
TI  - Medical care-seeking and health-risk behavior in patients with head and neck
      cancer: the role of health value, control beliefs and psychological distress.
AB  - Health behavior plays an important role in the development, detection and course
      of cancer of the head and neck. Relevant health behavior includes prompt medical
      care seeking, and smoking and drinking cessation after diagnosis. This study
      examines the relationship between these health behaviors and health value and
      control beliefs, as well as psychological distress. Two hundred and sixty-four
      recently diagnosed head and neck cancer patients were interviewed about their
      health behavior, and they filled in a questionnaire on health beliefs and
      psychological distress. The results showed that one-quarter (25%) of the patients
      had waited more than 3 months before seeking medical care, 50% had continued to
      smoke and 80% had continued to drink after the diagnosis. The patients,
      particularly those who smoked and drank before diagnosis, reported lower levels
      of health value and perceived health competence than a general population sample
      with which they were compared. Patients who engaged in patient delay reported a
      lack of perceived health competence. Psychological distress and lack of perceived
      health competence were found to be more common among patients who continued to
      smoke. The implications of these findings are discussed with regard to
      interventions aimed at promoting these specific health behaviors.

PMID- 15863623
TI  - The THAP domain of THAP1 is a large C2CH module with zinc-dependent sequence
      specific DNA-binding activity.
AB  - We have recently described an evolutionarily conserved protein motif, designated
      the THAP domain, which defines a previously uncharacterized family of cellular
      factors (THAP proteins). The THAP domain exhibits similarities to the site
      specific DNA-binding domain of Drosophila P element transposase, including a
      putative metal-coordinating C2CH signature (CX(2-4)CX(35-53)CX(2)H). In this
      article, we report a comprehensive list of approximately 100 distinct THAP
      proteins in model animal organisms, including human nuclear proapoptotic factors
      THAP1 and DAP4/THAP0, transcriptional repressor THAP7, zebrafish orthologue of
      cell cycle regulator E2F6, and Caenorhabditis elegans chromatin-associated
      protein HIM-17 and cell-cycle regulators LIN-36 and LIN-15B. In addition, we
      demonstrate the biochemical function of the THAP domain as a zinc-dependent
      sequence-specific DNA-binding domain belonging to the zinc-finger superfamily. In
      vitro binding-site selection allowed us to identify an 11-nucleotide consensus
      DNA-binding sequence specifically recognized by the THAP domain of human THAP1.
      Mutations of single nucleotide positions in this sequence abrogated THAP-domain
      binding. Experiments with the zinc chelator 1,10-o-phenanthroline revealed that
      the THAP domain is a zinc-dependent DNA-binding domain. Site-directed mutagenesis
      of single cysteine or histidine residues supported a role for the C2CH motif in
      zinc coordination and DNA-binding activity. The four other conserved residues (P,
      W, F, and P), which define the THAP consensus sequence, were also found to be
      required for DNA binding. Together with previous genetic data obtained in C.
      elegans, our results suggest that cellular THAP proteins may function as zinc
      dependent sequence-specific DNA-binding factors with roles in proliferation,
      apoptosis, cell cycle, chromosome segregation, chromatin modification, and
      transcriptional regulation.

PMID- 15863625
TI  - Obesity in children and adolescents.

PMID- 15863626
TI  - Divorce and the adjustment of children.

PMID- 15863627
TI  - A multicultural approach to the patient who has a common cold.

PMID- 15863628
TI  - Visual diagnosis: a 15-year-old female who has cough, rash, and painful swallow.

PMID- 15863629
TI  - Index of suspicion.

PMID- 15863630
TI  - Lipopolysaccharide and the lung: a story of love and hate.

PMID- 15863631
TI  - Deciphering the "matrix" in pulmonary vascular remodelling.

PMID- 15863632
TI  - The vascular micromilieu in obstructive sleep apnoea.

PMID- 15863633
TI  - Pulmonary hypertension in advanced sarcoidosis: epidemiology and clinical
      characteristics.
AB  - Pulmonary hypertension (PH) is a predictor of poor outcome in sarcoidosis. Little
      is known about the epidemiology of PH in sarcoidosis. The current authors
      reviewed the records of patients with sarcoidosis listed for lung transplantation
      in the USA between January 1995 and December 2002. PH was defined as a mean
      pulmonary artery pressure of >25 mmHg and severe PH as a mean pulmonary artery
      pressure of > or =40 mmHg. The cohort included 363 patients of whom 73.8% had PH.
      Neither spirometric testing nor the need for corticosteroids was associated with
      PH. Subjects with PH required more supplemental oxygen (2.7+/-1.8 L.min(-1)
      versus 1.6+/-1.4 L.min(-1)). The cardiac index was lower in individuals with PH,
      whereas the pulmonary capillary wedge pressure was higher. In multivariate
      analysis, supplemental oxygen remained an independent predictor of PH, whereas
      the relationship between cardiac index and PH was no longer significant. As a
      screening test, the need for oxygen had a sensitivity and specificity of 91.8%
      and 32.6%, respectively. Pulmonary hypertension is common in advanced
      sarcoidosis. The need for oxygen correlates with pulmonary hypertension. Since
      pulmonary hypertension is associated with poor outcomes and because simple
      clinical criteria fail to identify patients with sarcoidosis and pulmonary
      hypertension, more aggressive screening for this should be considered.

PMID- 15863634
TI  - LPS-induced lung inflammation is linked to increased epithelial permeability:
      role of MLCK.
AB  - The respiratory system is directly exposed to low levels of lipopolysaccharide
      (LPS), present as a contaminant on airborne particles. In cystic fibrosis, the
      prevailing data identify structural changes of the airway epithelium, as well as
      tight junction dilatation. This study was aimed at determining the contribution
      of myosin light chain kinase to maintaining airway epithelium barrier integrity
      in the lung inflammatory response to LPS in rats. The effects of the selective
      myosin light chain kinase inhibitor, 5-iodonaphthalene-1-sulphonyl-homopiperazine
      (ML-7), were evaluated: 1) on pulmonary inflammation and airway epithelium
      barrier permeability alterations induced by intra-tracheal LPS from Pseudomonas
      aeruginosa; and 2) on levels of the phosphorylated form of the myosin light
      chain, which is increased in a human airway epithelial cell line (NCI-H292) and
      tracheal tissue after LPS exposure. The results show that LPS increased airway
      epithelium barrier paracellular permeability and lung inflammation, and that pre
      treatment with ML-7 inhibited both effects. This effect of ML-7 was associated
      with the inhibition of phosphorylated myosin light chain in both NCI-H292 cells
      and tracheal tissue. The data, obtained using in vivo and in vitro approaches,
      demonstrate a key role for myosin light chain kinase in lung inflammation, and
      suggest that myosin light chain kinase could be a potential target for novel
      drugs intended for relief of lung injury.

PMID- 15863635
TI  - Increased expression of p38 MAPK in human bronchial epithelium after
      lipopolysaccharide exposure.
AB  - Bacterial endotoxin (lipopolysaccharides (LPS)) is normally present in the wall
      of Gram-negative bacteria and has potent pro-inflammatory properties. Exposure to
      LPS has been shown to induce neutrophilic airway inflammation in humans. The aim
      of this investigation was to study the early inflammatory responses to LPS
      exposure in human airway mucosa in vivo. In total, 15 healthy nonsmoking
      volunteers participated. Bronchoscopy was performed on two separate occasions, 3
      h after saline inhalation and after inhalation of 50 mug LPS in saline.
      Endobronchial mucosal biopsy specimens were taken and stained
      immunohistochemically using a panel of monoclonal antibodies directed against
      mitogen-activated protein kinases (MAPKs), transcription factors, cytokines,
      adhesion molecules and inflammatory cells. Expression of p38 MAPK increased as a
      consequence of LPS exposure, as determined by both total epithelial staining and
      nuclear location. These two responses were strongly associated. Epithelial
      expression of interleukin-8 showed a tendency towards a significant increase
      after LPS compared to saline. Epithelial mast cell numbers were increased after
      LPS, whereas neutrophil numbers were unchanged. Inhalation of lipopolysaccharide
      induced activation of the bronchial epithelium, as demonstrated 3 h after
      exposure by increased expression of p38 mitogen-activated protein kinase and
      interleukin-8, and may represent early regulatory steps in the subsequent
      development of a neutrophilic bronchial inflammation.

PMID- 15863636
TI  - C-reactive protein as a marker of ventilator-associated pneumonia resolution: a
      pilot study.
AB  - The aim of this study was to evaluate C-reactive protein (CRP) levels, body
      temperature and white cell count (WCC) after prescription of antibiotics in order
      to describe the clinical resolution of ventilator-associated pneumonia (VAP). A
      cohort of 47 VAP patients with microbiological confirmation of disease was
      assessed. CRP levels, body temperature and WCC were monitored daily. On day 4 of
      the antibiotic therapy, the CRP level of survivors was 0.62 times the initial
      value, whereas, in nonsurvivors, it was 0.98. Body temperature and WCC remained
      almost unchanged. By day 4, a CRP of >0.6 times the initial level was a marker of
      poor outcome (sensitivity 0.92; specificity 0.59). Patients were divided
      according to their CRP patterns of response to antibiotics: fast response, slow
      response, nonresponse, and biphasic response. All patients with fast and slow
      response patterns survived, whereas those showing nonresponse and a biphasic
      response pattern exhibited a mortality of 78 and 75%, respectively. The adequacy
      of the initial antibiotic therapy had a marked influence on the rate of CRP
      decrease, as well as on mortality. In conclusion, daily C-reactive protein
      measurements after antibiotic prescription were useful in the identification, as
      early as day 4, of ventilator-associated pneumonia patients with poor outcome.
      The identification of the pattern of C-reactive protein response to antibiotics
      was useful in the recognition of individual clinical course, improving or
      worsening, as well as of the rate of improvement.

PMID- 15863637
TI  - Exhaled NO may predict the decline in lung function in bronchiolitis obliterans
      syndrome.
AB  - Bronchiolitis obliterans syndrome (BOS) remains the leading cause of
      morbidity/mortality following lung transplantation. In recipients with BOS,
      markers predicting the decline in lung function are needed. The aim of this
      longitudinal study was to determine whether exhaled nitric oxide fraction (FeNO)
      measurements provide useful information for discriminating patients with unstable
      BOS from those with stable BOS. During a 14-month period, 145 FeNO measurements
      were performed in 50 lung transplant recipients. Among them, 16 recipients with
      BOS (32 FeNO measurements) were analysed. For each FeNO measurement, the patients
      were classified into three groups according to the decline in forced expiratory
      volume in one second (FEV1) within the following 6 months: 1) stable BOS free; 2)
      stable BOS (decline in FEV1 of <5%); and 3) unstable BOS (decline in FEV1 of > or
      =15%). The mean FeNO in patients with unstable BOS was significantly increased
      compared with that in stable BOS-free patients (18.4+/-5.7 versus 9.7+/-3.7 ppb)
      and that in patients with stable BOS (18.4+/-5.7 versus 9.7+/-3.3 ppb). The
      present findings suggest that, in patients with bronchiolitis obliterans
      syndrome, a raised exhaled nitric oxide fraction may predict the development of
      worrisome functional impairment during long-term follow-up.

PMID- 15863639
TI  - Cheyne-Stokes respiration and supine dependency.
AB  - The influence of position during sleep on central apnoeas during Cheyne-Stokes
      respiration has not previously been studied systematically. The current authors
      aimed to study the effect of body position and sleep stages on central sleep
      apnoeas during Cheyne-Stokes respiration. A total of 20 consecutive patients with
      cardiovascular diseases and central sleep apnoea during Cheyne-Stokes respiration
      were investigated using nocturnal polysomnography, including a body position
      sensor mounted on the patient's sternum. The mean central apnoea-hypopnoea index
      was significantly higher in the supine position than in nonsupine positions (41+/
      13 versus 26+/-12). The central apnoea-hypopnoea index was highest in sleep
      stages 1 and 2, and lowest in slow-wave sleep and rapid eye movement sleep. In
      every sleep stage, central apnoeas and hypopnoeas were more prevalent in the
      supine position compared with nonsupine positions. In conclusion, sleep in the
      supine body position increases the frequency of apnoeas and hypopnoeas in
      patients with Cheyne-Stokes respiration.

PMID- 15863638
TI  - Activated CD8+ T-lymphocytes in obstructive sleep apnoea.
AB  - T-lymphocytes are implicated in the development of atherosclerosis. The aim of
      this study was to assess whether the CD8+ T-lymphocytes of obstructive sleep
      apnoea (OSA) patients undergo phenotypic and functional changes that may
      exaggerate atherogenic sequelae in OSA. A total of 36 OSA patients, 17 controls
      and 15 single-night-treated OSA patients were studied. Phenotype and cytotoxicity
      against K562 target cells were analysed by flow cytometry. Cytotoxicity against
      human umbilical vein endothelial cells (HUVECs) was assessed by 51Cr release
      assay. The cytotoxicity of the CD8+ T-lymphocytes of OSA patients against K562
      and HUVECs was significantly greater than controls. This increased cytotoxicity
      directly depended on the presence of perforin and natural killer receptors (CD56,
      CD16), which were significantly increased in OSA CD8+ T-lymphocytes. Also the
      percentage of the CD56bright subset, which mediates initial interactions with
      vascular endothelium, significantly increased in OSA. Nasal continuous positive
      airway pressure treatment significantly decreased CD8+ T-cell cytotoxicity and
      CD56 expression, and was positively correlated with natural killer inhibitory
      NKB1 receptor expression either after a single-night treatment or after a
      prolonged treatment. In conclusion, the CD8+ T-lymphocytes of obstructive sleep
      apnoea patients undergo phenotypic and functional changes, rendering them
      cytotoxic to target cells via increased CD56+/perforin+ expression, which can be
      ameliorated by nasal continuous positive airway pressure treatment. These results
      are compatible with the current authors' hypothesis of atherogenic sequelae in
      obstructive sleep apnoea.

PMID- 15863640
TI  - Smooth muscle cell matrix metalloproteinases in idiopathic pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) results from persistent vasoconstriction,
      smooth muscle growth and extracellular matrix (ECM) remodelling of pulmonary
      arteries (PAs). Matrix metalloproteinases (MMPs) are matrix-degrading enzymes
      involved in ECM turnover, and in smooth muscle cell (SMC) and endothelial cell
      migration and proliferation. MMP expression and activity are increased in
      experimental PAH. Therefore, this study investigated whether similar changes
      occur in idiopathic PAH (IPAH; formerly known as primary pulmonary hypertension).
      Both in situ and in vitro studies were performed on PAs from patients undergoing
      lung transplantation for IPAH and from patients treated by lobectomy for
      localised lung cancer, who served as controls. In IPAH, MMP-tissue inhibitor of
      metalloproteinase (TIMP) imbalance was found in cultured PA-SMCs, with increased
      TIMP-1 and decreased MMP-3. MMP-2 activity was markedly elevated as a result of
      increases in both total MMP-2 and proportion of active MMP-2. In situ zymography
      and immunolocalisation showed that MMP-2 was associated with SMCs and elastic
      fibres, and also confirmed the MMP-3-TIMP-1 imbalance. In conclusion, the
      findings of this study were consistent with a role for the matrix
      metalloproteinase-tissue inhibitor of metalloproteinase system in pulmonary
      vascular remodelling in idiopathic pulmonary arterial hypertension. The matrix
      metalloproteinase-tissue inhibitor of metalloproteinase imbalance may lead to
      matrix accumulation, and increased matrix metalloproteinase-2 activity may
      contribute to smooth muscle cell migration and proliferation. Whether these
      abnormalities are potential therapeutic targets deserves further investigation.

PMID- 15863641
TI  - Prognostic value of the ECG on admission in patients with acute major pulmonary
      embolism.
AB  - A number of ECG abnormalities can be observed in the acute phase of pulmonary
      embolism (PE). Their prognostic value has not yet been systematically studied in
      large patient populations. In 508 patients with acute major PE derived from a
      large prospective registry, the current authors assessed, on admission, the
      impact of specific pathological ECG findings on early (30-day) mortality. Atrial
      arrhythmias, complete right bundle branch block, peripheral low voltage,
      pseudoinfarction pattern (Q waves) in leads III and aVF, and ST segment changes
      (elevation or depression) over the left precordial leads, were all significantly
      more frequent in patients with a fatal outcome. Overall, 29% of the patients who
      exhibited at least one of these abnormalities on admission did not survive to
      hospital discharge, as opposed to only 11% of the patients without a pathological
      12-lead ECG. Multivariate analysis revealed that the presence of at least one of
      the above ECG findings was, besides haemodynamic instability, syncope and pre
      existing chronic pulmonary disease, a significant independent predictor of
      outcome. In conclusion, ECG may be a useful, simple, non-costly tool for initial
      risk stratification of patients with acute major pulmonary embolism.

PMID- 15863642
TI  - The inositol trisphosphate pathway mediates platelet-activating-factor-induced
      pulmonary oedema.
AB  - Platelet-activating factor (PAF) is a pro-inflammatory lipid mediator that
      increases vascular permeability by simultaneous activation of two pathways, one
      dependent on the cyclooxygenase metabolite prostaglandin E2 and the other on the
      sphingomyelinase metabolite ceramide. The hypothesis that part of the PAF-induced
      oedema is mediated via the inositol 1,4,5-trisphosphate (IP3) pathway or Rho
      kinase pathway was investigated. Oedema formation was induced in isolated
      perfused rat lungs by injection of 5 nmol PAF into the pulmonary artery. Lungs
      were pre-treated with specific inhibitors: edelfosine (L108) to block
      phosphatidyl-inositol-specific phospholipase C, xestospongin to block the IP3
      receptor, 5-iodonaphthalene-1-sulphonyl-homopiperazine (ML-7) to block myosin
      light chain kinase, and (+)-R-trans-4-(aminoethyl)-N-(4
      pyridyl)cyclohexanecarboxamide (Y27632) to block Rho-associated protein kinase.
      Pre-treatment with L108 or xestospongin reduced PAF-induced oedema formation by
      58 and 56%, respectively. The effect of L108 was additive to that of the
      cyclooxygenase inhibitor acetyl salicylic acid (88% oedema reduction). PAF
      induced oedema formation was also reduced if extracellular calcium concentrations
      were lowered. Furthermore, treatment with ML-7 reduced oedema formation by 54%,
      whereas Y27632 was without effect. It is concluded that platelet-activating
      factor-triggered oedema is mediated by activation of the inositol 1,4,5
      trisphosphate pathway, influx of extracellular calcium and subsequent activation
      of a myosin light chain kinase-dependent and Rho-associated-protein-kinase
      independent mechanism.

PMID- 15863643
TI  - Activation of human lung mast cells by monomeric immunoglobulin E.
AB  - The mechanism of chronic mast cell activation in asthma is unclear. Monomeric
      immunoglobulin (Ig)E in the absence of allergen induces mediator release from
      rodent mast cells, indicating a possible role for IgE in the continued activation
      of mast cells within the asthmatic bronchial mucosa. In this study it was
      investigated whether monomeric IgE induces Ca2+ influx and mediator release from
      human lung mast cells (HLMC). Purified HLMC were cultured for 4 weeks and then
      exposed to monomeric human myeloma IgE. Ratiometric Ca2+ imaging was performed on
      single fura-2-loaded cells. Histamine release was measured by radioenzymatic
      assay; leukotriene C4 (LTC4) and interleukin (IL)-8 were measured by ELISA. At
      concentrations experienced in vivo, monomeric IgE induced dose-dependent
      histamine release, LTC4 production and IL-8 synthesis. This was associated with a
      rise in cytosolic free Ca2+. Enhanced histamine release was still evident 1 week
      after initial exposure to IgE suggesting that continued exposure maintains
      enhanced secretion. Monomeric immunoglobulin E alone activates cultured human
      lung mast cells initiating Ca2+ influx, degranulation, arachidonic acid
      metabolism and cytokine synthesis. These findings support the hypothesis that
      immunoglobulin E loading of mast cells within the asthmatic airway contributes to
      the disordered airway physiology of this disease.

PMID- 15863644
TI  - Effects of salbutamol and enantiomers on allergen-induced asthmatic reactions and
      airway hyperreactivity.
AB  - Salbutamol consists of a racemic mixture of R- and S-salbutamol. R-salbutamol
      (levalbuterol) is the active bronchodilating enantiomer, whereas S-salbutamol is
      thought to be pharmacologically inactive or to exert adverse effects. This study
      evaluated the bronchoprotective effects of inhalation of therapeutically relevant
      doses of the racemate and individual enantiomers in guinea pigs. It was found
      that basal airway reactivity to histamine was similarly reduced 30 min after
      inhalation of equivalent doses of RS- and R-salbutamol; this protective effect
      disappeared within 3 h. Inhalation of RS- and R-salbutamol 30 min before and 5.5
      h after allergen challenge suppressed allergen-induced airway hyperreactivity to
      histamine after the early and late asthmatic reaction, completely inhibiting the
      early asthmatic reaction and tending to reduce the development of the late
      asthmatic reaction. At 5 h after allergen challenge, the inhibition of airway
      hyperreactivity was more pronounced in animals treated with R-salbutamol compared
      to racemate-treated animals. Both basal airway reactivity and allergen-induced
      hyperreactivity were not affected by S-salbutamol. Inflammatory cell infiltration
      was not affected by the racemate or the individual enantiomers. In conclusion,
      inhalation of therapeutically relevant doses of R- and RS-salbutamol effectively
      suppress allergen-induced airway reactivity after the early and late asthmatic
      reactions, the R-enantiomer being slightly more potent with respect to early
      airway reactivity than the racemate. No adverse effects were observed for the S
      enantiomer.

PMID- 15863645
TI  - Adenosine level in exhaled breath increases during exercise-induced
      bronchoconstriction.
AB  - In asthmatic patients, airway obstruction provoked by exercise challenge is
      accompanied by an increase in plasma adenosine level. In this study, the current
      authors investigated if exercise-induced bronchoconstriction was associated with
      local changes of adenosine concentration in the airways. Oral exhaled breath
      condensate (EBC) collection (5-min duration) and forced expiratory volume in one
      second (FEV1) measurements were performed at rest (baseline) and 4-8 times after
      treadmill exercise challenge in healthy and asthmatic subjects. Adenosine
      concentration in EBC was determined by HPLC. Observations indicated that physical
      exercise results in bronchoconstriction together with a significant increase of
      adenosine level in EBC in asthmatic patients (mean+/-sd maximal fall in FEV1 27+/
      13%; associated increase in adenosine 110+/-76% as compared to baseline), but not
      in healthy control subjects. Exercise-induced changes in adenosine concentration
      correlated significantly with the fall in FEV1 values in asthmatic patients. In
      conclusion, the observed increase in adenosine concentration of oral exhaled
      breath condensate most probably reflects changes in the airways during exercise
      induced bronchoconstriction. Due to its known bronchoconstrictor property in
      asthma, adenosine may contribute to the development of bronchospasm.

PMID- 15863646
TI  - Severity of obstructive airway disease and risk of osteoporotic fracture.
AB  - The use of inhaled corticosteroids has been associated with a dose-related
      increased risk of fracture. This may be related to systemic absorption. However,
      several studies have found that patients with more severe reductions in pulmonary
      function had reduced bone mineral density, independent of inhaled
      corticosteroids. The objective of this study was to evaluate the relationship
      between disease severity and fracture risk. A large case-control study (108,754
      cases) was conducted using data from the UK General Practice Research Database.
      It was found that higher doses of inhaled corticosteroids were associated with
      greater risks of fracture. The crude odds ratio of fracture among patients
      exposed to >1,600 microg beclomethasone equivalents per day was 1.95 (95%
      confidence interval (CI) 1.68-2.27). When adjustments were made for disease
      severity and use of bronchodilators, the initial dose-response relationship
      between inhaled corticosteroids and fracture risk disappeared (adjusted odds
      ratio of 1.19 (95% CI 1.01-1.41)). In conclusion, patients with severe
      obstructive airway disease are at risk of fracture. However, adequate adjustment
      for disease severity is essential when the association between the use of inhaled
      corticosteroids and risk of osteoporotic fracture is studied in observational
      research.

PMID- 15863647
TI  - Increased serum concentrations of tissue inhibitor of metalloproteinase-1 in COPD
      patients.
AB  - Matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinase
      (TIMP)-1 concentrations are increased in the sputum of asthma and chronic
      bronchitis patients, and are thought to be related to airflow obstruction.
      However, serum concentrations of these enzymes have not been clearly evaluated in
      patients with chronic obstructive pulmonary disease (COPD). The aim of this study
      was to examine the serum concentrations of these enzymes in COPD and asthmatic
      patients in order to determine their relationship with airway obstruction. Serum
      samples were obtained from 72 patients with COPD: 66 control subjects and 26
      patients with asthma. Smoking histories of control subjects were matched with
      those of COPD patients. Serum concentrations of TIMP-1 and MMP-9 were determined
      by ELISA. The circulating TIMP-1 concentration was significantly higher in stable
      COPD patients than in control and asthmatic subjects, and was significantly
      negatively correlated with forced expiratory volume in one second/forced vital
      capacity in COPD patients. The molar ratio between MMP-9 and TIMP-1 was
      significantly lower in COPD patients than in control subjects. In patients with
      COPD, the serum TIMP-1 concentration was significantly increased during disease
      exacerbation. In conclusion, the current findings suggest that serum tissue
      inhibitors of metalloproteinase-1 concentration can be used as a serum marker of
      airway obstruction and exacerbation in chronic obstructive pulmonary disease
      patients.

PMID- 15863648
TI  - Standardised mortality rates in females and males with COPD and asthma.
AB  - Mortality studies of males and females with chronic obstructive pulmonary disease
      (COPD) and asthma have suggested that females have a poorer prognosis than males,
      but the results are either not unanimous or based on poorly characterised
      patients. The current study analysed the mortality of 279 asthma patients and 869
      COPD patients, who were seeking pension due to disability, and compared mortality
      rates with expected rates derived from the general population. The mean follow-up
      period was 13.3 yrs (range 2.5-22.4 yrs) during which time 96 (34.4%) and 671
      (77.2%) deaths were identified among asthma and COPD patients, respectively. The
      average age at study entry was 46.8 and 56.6 yrs, and the average forced
      expiratory volume in one second (FEV1) was 68.8 and 44.1 % predicted in the two
      diagnostic groups. After adjustment for predictors of survival (age, FEV1 %
      predicted, chronic bronchitis, body mass index, smoking status, oral
      prednisolone, ischaemic heart disease, and cor pulmonale), the relative risk of
      death was 1.21 (95% confidence interval: 0.77-1.89) and 0.98 (0.83-1.16) in
      females compared with males, in asthma and COPD patients, respectively. The
      standardised mortality rate (SMR) for males was 1.54 (1.10-2.09) and 2.7 (2.5
      3.0), and for females 1.91 (1.44-2.49) and 4.8 (4.2-5.4), in asthma and COPD
      patients, respectively. Direct comparison of the SMR of males and females showed
      that females had higher mortality than males, with a rate ratio of 1.24 (0.82
      1.84) and 1.8 (1.5-2.0), in asthma and COPD patients, respectively. Poisson
      regression analysis with control for the confounders did not change this result.
      Females and males with the same level of obstructive lung disease appear to have
      the same level of mortality. However, using standardised mortality rates, females
      have a higher mortality than males, suggesting that the protective effect of
      being female is lost in chronic obstructive pulmonary disease patients.

PMID- 15863649
TI  - The effects of body weight on airway calibre.
AB  - Increased wheeze and asthma diagnosis in obesity may be due to reduced lung
      volume with subsequent airway narrowing. Asthma (wheeze and airway
      hyperresponsiveness), functional residual capacity (FRC) and airway conductance
      (Gaw) were measured in 276 randomly selected subjects aged 28-30 yrs. Data were
      initially adjusted for smoking and asthma before examining relationships between
      weight and FRC (after adjustment for height), and between body mass index (BMI =
      weight.height(-2)) and Gaw (after adjustment for FRC) by multiple linear
      regression, separately for females and males. For males and females, BMI (+/-95%
      confidence interval) was 27.0+/-4.6 kg.m(-2) and 25.6+/-6.0 kg.m(-2)
      respectively, Gaw was 0.64+/-0.04 L.s(-1).cmH2O(-1) and 0.57+/-0.03 L.s(
      1).cmH2O(-1), and FRC was 85.3+/-3.4 and 84.0+/-2.9% of predicted. Weight
      correlated independently with FRC in males and females. BMI correlated
      independently and inversely with Gaw in males, but only weakly in females. In
      conclusion, obesity is associated with reduced lung volume, which is linked with
      airway narrowing. However, in males, airway narrowing is greater than that due to
      reduced lung volume alone. The mechanisms causing airway narrowing and sex
      differences in obesity are unknown.

PMID- 15863650
TI  - Human immune recognition-based multicomponent subunit vaccines against
      tuberculosis.
AB  - The cell-mediated immune response, with its shift in favour of type-1 over type-2
      T-helper cell immune response, is generally regarded as essential to protection
      against mycobacterial infections. The aim of this study was to evaluate the
      protective potential of two multicomponent subunit vaccines (MSV-1 and MSV-2)
      against tuberculosis (TB) based on human immune recognition. MSV-1 consisted of
      five immunodominant antigens (TB10.4, early secretory antigenic target (ESAT)-6,
      culture filtrate protein (CFP)-8, CFP-10 and CFP-15) selected from a group of
      polypeptides, which induced a predominant T-cell response in immune human
      subjects, whereas MSV-2 consisted of antigens (CFP-11, CFP-21, CFP-22.5,
      Mycobacterium tuberculosis protein (MPT)-64 and CFP-31) selected from a group of
      polypeptides which induced a subdominant T-cell response along with the antibody
      response. Both of these sets of polypeptides were extensively recognised in
      healthy individuals with significant interferon gamma release compared to the
      diseased population. In C57BL/6J mice, at the level of the lungs, the order of
      protective efficacy for the test vaccines was: bacille Calmette-Guerin (BCG)>MSV
      2>MSV-1. The protective efficacy of MSV-1 was found to be significantly less than
      that of MSV-2 and BCG at the level of spleen, whereas that of MSV-2 was
      comparable to that of BCG. The results of this study indicate that high T-helper
      cell type 1 response-inducing polypeptides selected on the basis of human immune
      recognition do not necessarily impart protection during vaccination experiments.

PMID- 15863651
TI  - Significance of positive Stenotrophomonas maltophilia culture in acute
      respiratory tract infection.
AB  - Stenotrophomonas maltophilia is a common coloniser of the respiratory tract of
      patients with chronic lung disease, and, in the absence of pneumonia or
      bacteraemia, is often ignored by physicians at the Royal Perth Hospital (Perth,
      Australia). Experience at the Royal Perth Hospital was reviewed to determine
      whether ignoring S. maltophilia in this setting has any apparent effect on
      clinical outcome. All patients who presented with an acute respiratory illness
      and yielded a positive culture for S. maltophilia between 1995 and 2002 were
      retrospectively reviewed. All subjects had to yield a positive respiratory
      isolate of S. maltophilia and undergo chest radiography within 24 h of the
      isolate being obtained. Ninety-two episodes were identified in 89 individuals; 64
      showed no evidence of consolidation. Of the study group, 51 (80.0%) received no
      anti-S. maltophilia antibiotic therapy and 21 (32.8%) had a nosocomially acquired
      isolate. The overall mortality rate was 20.3%. There was no impact of anti-S.
      maltophilia therapy on outcome. The only independent predictor of mortality was
      serum albumin level. As there was no measurable impact of antibiotic therapy, in
      the absence of consolidation, a positive respiratory tract isolate of
      Stenotrophomonas maltophilia probably represents colonisation of a severely
      impaired host rather than invasive disease.

PMID- 15863652
TI  - Genetics of fibrosing lung diseases.
AB  - Genetic studies in familial lung fibrosis have demonstrated an association with
      surfactant protein C genes: two mutations have been found resulting in protein
      misfolding and causing type-II epithelial cell injury. Remarkably, different
      histological patterns were observed in the affected subjects, suggesting the
      influence of modifier genes and/or environmental factors. Surfactant protein C
      gene variations have not, however, been associated with sporadic cases, i.e.
      idiopathic pulmonary fibrosis (IPF). Susceptibility to IPF probably involves a
      combination of polymorphisms related to epithelial cell injury and abnormal wound
      healing. To date, the genetic associations with IPF that have been reported in
      different cohorts include the genes encoding tumour necrosis factor (TNF; -308
      adenine), interleukin-1 receptor antagonist (+2018 thymidine) and association
      with severity and progression (interleukin-6/TNF receptor II and transforming
      growth factor-beta1 (TGFB1; +869 cytosine)), but none of these associations have
      been replicated by others. Unlike in IPF, immunological inflammation seems to be
      more prominent in the pathogenesis of scleroderma lung fibrosis, being an
      autoimmune disease with specific autoantibodies, such as antitopoisomerase
      antibodies, in patients with diffuse lung disease, and anticentromere antibodies,
      in patients with pulmonary vascular disease. Antitopoisomerase antibody
      positivity is associated with the carriage of human leukocyte antigen DRB1*11 and
      DPB1*1301 alleles, suggesting the recognition of a specific amino-acid motif.
      Extended haplotype analysis also supports the conclusion that TNF may be the
      primary association with anticentromere positivity. Intriguingly, associations
      with TGFB1 and genes involved in extracellular matrix homeostasis have been
      reported in this disease. In conclusion, significant steps forward have been
      taken in the understanding of the genetic contribution to fibrosing lung
      diseases, but major challenges lay ahead. It is the present authors' opinion that
      only a combined approach studying large numbers of familial and sporadic cases,
      all clinically well phenotyped, using multiple distinct cohorts, and genotyped
      according to relevant gene ontologies will be successful. It will be necessary to
      be particularly vigilant with regard to phenotype; the absence of very strong
      reproducible associations may be because of the rigidity of phenotype definition,
      coupled with the possibility that idiopathic pulmonary fibrosis may still be a
      heterogeneous group of diseases, despite the more rigid definition set out by the
      European Respiratory Society/American Thoracic Society statement.

PMID- 15863653
TI  - Management of multidrug-resistant tuberculosis and patients in retreatment.
AB  - Retreatment of tuberculosis involves the management of entities as diverse as
      relapse, failure, treatment after default, and poor patient adherence to the
      previous treatment. The emergence of conditions for selection of resistance
      (failure and partial abandonment) is a matter of great concern. The development
      of a retreatment regimen for tuberculosis requires consideration of certain basic
      premises. The importance of a comprehensive and directed history of drugs taken
      in the past, and the limited reliability of susceptibility tests to many of these
      drugs, should be kept in mind. Taking this into account, and possessing a
      thorough knowledge of all anti-tuberculosis medications, it is possible to cure
      almost all patients with an appropriate retreatment regimen including a minimum
      of three or four drugs not previously used. Nonetheless, the treatment of these
      patients is so complex that it should only be carried out by experienced staff.
      Concern about treating tuberculosis patients with drug resistance varies greatly
      depending on the available resources. High-income countries should provide
      individual treatment regimens adapted to each patient; however, in other
      settings, restricted resources could justify the implementation of standardised
      therapeutic guidelines with second-line drugs in order to facilitate management
      and reduce costs.

PMID- 15863654
TI  - A 29-year-old male with malaise, chest pain and night sweats.

PMID- 15863656
TI  - BRCA1 mutation and neuronal migration defect: implications for chemoprevention.

PMID- 15863657
TI  - Pitfalls of automated comparative sequence analysis as a single platform for
      routine clinical testing for NF1.

PMID- 15863658
TI  - Is maternal duplication of 11p15 associated with Silver-Russell syndrome?
AB  - BACKGROUND: Silver-Russell syndrome (SRS) is a heterogeneous malformation
      syndrome characterised by intrauterine and postnatal growth retardation (IUGR,
      PGR) and dysmorphisms. The basic causes are unknown, however in approximately 10%
      of patients a maternal uniparental disomy (UPD) of chromosome 7 or chromosomal
      aberrations can be detected. Four growth retarded children, two with SRS-like
      features, associated with maternal duplications of 11p15 have been described.
      Considering the involvement of this genomic region in Beckwith-Wiedemann
      overgrowth syndrome (BWS), we postulated that some cases of SRS--with an opposite
      phenotype to BWS--might also be caused by genomic disturbances in 11p15. METHODS:
      A total of 46 SRS patients were screened for genomic rearrangements in 11p15 by
      STR typing and FISH analysis. RESULTS: Two SRS patients with duplications of
      maternal 11p material in our study population (n = 46) were detected. In patient
      SR46, the duplicated region covered at least 9 Mb; FISH analysis revealed a
      translocation of 11p15 onto 10q. In patient SR90, additional 11p15 material
      (approximately 5 Mb) was translocated to the short arm of chromosome 15.
      CONCLUSIONS: We suggest that diagnostic testing for duplication in 11p15 should
      be offered to patients with severe IUGR and PGR with clinical signs reminiscent
      of SRS. SRS is a genetically heterogeneous condition and patients with a maternal
      duplication of 11p15.5 may form an important subgroup.

PMID- 15863659
TI  - BRCA1:185delAG found in the San Luis Valley probably originated in a Jewish
      founder.

PMID- 15863660
TI  - Novel mutations in COX15 in a long surviving Leigh syndrome patient with
      cytochrome c oxidase deficiency.
AB  - BACKGROUND: Isolated cytochrome c oxidase (COX) deficiency is usually associated
      with mutations in several factors involved in the biogenesis of COX. METHODS: We
      describe a patient with atypical, long surviving Leigh syndrome carrying two
      novel mutations in the COX15 gene, which encodes an enzyme involved in the
      biosynthesis of heme A. RESULTS: Only two COX15 mutated patients, one with severe
      neonatal cardiomyopathy, the other with rapidly fatal Leigh syndrome, have been
      described to date. In contrast, our patient had a slowly progressive course with
      no heart involvement. COX deficiency was mild in muscle and a normal amount of
      fully assembled COX was present in cultured fibroblasts. CONCLUSIONS: The
      clinical and biochemical phenotypes in COX15 defects are more heterogeneous than
      in other conditions associated with COX deficiency, such as mutations in SURF1.

PMID- 15863661
TI  - Unconventional intronic splice site mutation in SCN5A associates with cardiac
      sodium channelopathy.
AB  - BACKGROUND: Mutations in the cardiac sodium channel, SCN5A, have been associated
      with one type of long-QT syndrome, with isolated cardiac conduction defects and
      Brugada syndrome. The sodium channelopathies exhibit marked variation in clinical
      phenotypes. The mechanisms underlying the phenotypical diversity, however, remain
      unknown. Exonic SCN5A mutations can be detected in 20% of Brugada syndrome
      patients. RESULTS: An intronic mutation (c.4810+3_4810+6dupGGGT) in the SCN5A
      gene, located outside the consensus splice site, was detected in this study in a
      family with a highly variable clinical phenotype of Brugada syndrome and/or
      conduction disease and in a patient with Brugada syndrome. The mutation was not
      found in a control panel of 100 (200 alleles) ethnically matched normal control
      subjects. We provide in vivo and in vitro evidence that the mutation can disrupt
      the splice donor site, activate a cryptic splice site, and create a novel splice
      site. Notably, our data show that normal transcripts can be also derived from the
      mutant allele. CONCLUSIONS: This is the first report of an unconventional
      intronic splice site mutation in the SCN5A gene leading to cardiac sodium
      channelopathy. We speculate that its phenotypical diversity might be determined
      by the ratio of normal/abnormal transcripts derived from the mutant allele.

PMID- 15863662
TI  - Search for genetic variants associated with cutaneous malignant melanoma in the
      Ashkenazi Jewish population.

PMID- 15863663
TI  - Large genomic rearrangements of both BRCA2 and BRCA1 are a feature of the
      inherited breast/ovarian cancer phenotype in selected families.
AB  - INTRODUCTION: A strong family history of breast and/or ovarian cancer can often
      be explained by small insertions, deletions, or substitutions in BRCA1 or BRCA2
      and large genomic rearrangements in BRCA1. However, there is little evidence that
      genomic rearrangements are a major factor in BRCA2 associated breast cancer and
      the frequencies of rearrangements in BRCA1 in large clinic based populations are
      unknown. OBJECTIVE: To investigate the frequency of large genomic rearrangements
      in BRCA1 and BRCA2 in a large clinic based population at high risk of developing
      breast and/or ovarian cancer. METHODS: Multiplex ligation dependent probe
      amplification was used to comprehensively screen BRCA1 and/or BRCA2 in 312 index
      cases. RESULTS: Three novel deletions detected in BRCA2 were found exclusively in
      families with at least one case of male breast cancer. Novel rearrangements in
      BRCA1 were detected mostly in families with both breast and ovarian cancer.
      Families with these mutations were significantly younger at average age of cancer
      diagnosis. CONCLUSION: Screening for large genomic rearrangements in both BRCA1
      and BRCA2 is strongly supported by this study, in particular in multiple case
      breast/ovarian families with a young age of onset (BRCA1) and families containing
      at least one case of male breast cancer (BRCA2).

PMID- 15863664
TI  - GATA4 zinc finger mutations as a molecular rationale for septation defects of the
      human heart.

PMID- 15863665
TI  - Genetics of the polymicrogyria syndromes.
AB  - Polymicrogyria is a relatively common malformation of cortical development,
      characterised by multiple small gyri with abnormal cortical lamination. The
      different forms of polymicrogyria encompass a wide range of clinical,
      aetiological, and histological findings. Advances in imaging have improved the
      diagnosis and classification of the condition. The molecular basis of
      polymicrogyria is beginning to be elucidated with the identification of a gene,
      GPR56, for bilateral frontoparietal polymicrogyria. Functional studies of the
      GPR56 gene product will yield insights not only into the causes of polymicrogyria
      but also into the mechanisms of normal cortical development and the regional
      patterning of the cerebral cortex. Based on imaging studies, several other region
      specific patterns of polymicrogyria have been identified, and there is increasing
      evidence that these may also have a significant genetic component to their
      aetiology. This paper reviews current knowledge of the different polymicrogyria
      syndromes, with discussion of clinical and imaging features, patterns of
      inheritance, currently mapped loci, candidate genes, chromosomal abnormalities,
      and implications for genetic counselling.

PMID- 15863667
TI  - Reverse cascade screening of newborns for hereditary haemochromatosis: a model
      for other late onset diseases?
AB  - BACKGROUND: Genetic testing can determine those at risk for hereditary
      haemochromatosis (HH) caused by HFE mutations before the onset of symptoms.
      However, there is no optimum screening strategy, mainly owing to the variable
      penetrance in those who are homozygous for the HFE Cys282Tyr (C282Y) mutation.
      The objective of this study was to identify the majority of individuals at
      serious risk of developing HFE haemochromatosis before they developed life
      threatening complications. METHODS: We first estimated the therapeutic penetrance
      of the C282Y mutation in people living in la Somme, France, using genetic,
      demographic, biochemical, and follow up data. We examined the benefits of
      neonatal screening on the basis of increased risk to relatives of newborns
      carrying one or two copies of the C282Y mutation. Between 1999 and 2002, we
      screened 7038 newborns from two maternity hospitals in the north of France for
      the C282Y and His63Asp (H63D) mutations in the HFE gene, using bloodspots
      collected on Guthrie cards. Family studies and genetic counselling were
      undertaken, based on the results of the baby's genotype. FINDINGS: In la Somme,
      we found that 24% of the adults homozygous for the C282Y mutation required at
      least 5 g iron to be removed to restore normal iron parameters (that is, the
      therapeutic penetrance). In the reverse cascade screening study, we identified 19
      C282Y homozygotes (1/370), 491 heterozygotes (1/14) and 166 compound
      heterozygotes (1/42) in 7038 newborns tested. The reverse cascade screening
      strategy resulted in 80 adults being screened for both mutations. We identified
      10 previously unknown C282Y homozygotes of whom six (four men and two women)
      required venesection. Acceptance of neonatal screening was high; parents
      understood the risks of having HH and the benefits of early detection, but a
      number of parents were reluctant to take the test themselves. Neonatal screening
      for HH is straightforward. Reverse cascade screening increased the efficiency of
      detecting affected adults with undiagnosed haemochromatosis. This strategy allows
      almost complete coverage for HH and could be a model for efficient screening for
      other late onset genetic diseases.

PMID- 15863666
TI  - Genetics of congenital hypothyroidism.
AB  - Congenital hypothyroidism is the most common neonatal metabolic disorder and
      results in severe neurodevelopmental impairment and infertility if untreated.
      Congenital hypothyroidism is usually sporadic but up to 2% of thyroid dysgenesis
      is familial, and congenital hypothyroidism caused by organification defects is
      often recessively inherited. The candidate genes associated with this genetically
      heterogeneous disorder form two main groups: those causing thyroid gland
      dysgenesis and those causing dyshormonogenesis. Genes associated with thyroid
      gland dysgenesis include the TSH receptor in non-syndromic congenital
      hypothyroidism, and Gsalpha and the thyroid transcription factors (TTF-1, TTF-2,
      and Pax-8), associated with different complex syndromes that include congenital
      hypothyroidism. Among those causing dyshormonogenesis, the thyroid peroxidase and
      thyroglobulin genes were initially described, and more recently PDS (Pendred
      syndrome), NIS (sodium iodide symporter), and THOX2 (thyroid oxidase 2) gene
      defects. There is also early evidence for a third group of congenital hypothyroid
      conditions associated with iodothyronine transporter defects associated with
      severe neurological sequelae. This review focuses on the genetic aspects of
      primary congenital hypothyroidism.

PMID- 15863668
TI  - Angiotensin II type I receptor gene polymorphism: anthropometric and metabolic
      syndrome traits.
AB  - BACKGROUND: The renin angiotensin system is important in the regulation of
      vascular tone and fluid and electrolyte balance. The angiotensin converting
      enzyme gene (ACE) genotype has been shown to affect exercise response and glucose
      load response dependent on birth weight. Angiotensin II type I receptor (AGTR1)
      A1166C has previously been associated with the development of hypertension and
      coronary disease, but its metabolic effects have not been investigated. METHOD:
      AGTR1 A1166C was genotyped by allele specific PCR in 378 individuals from
      Hertfordshire, UK, who had been characterised for metabolic syndrome traits.
      RESULTS: Genotype counts were: AA, 183; AC, 170; CC, 25, consistent with Hardy
      Weinberg equilibrium. The CC genotype was associated with significantly lower
      body mass index (by 1.7 units) in men (p = 0.03), and the same magnitude effect
      in women with significant lower weight in both genders (p = 0.01), also lower
      waist circumference and waist-hip ratio (p = 0.01) in men, with a trend for lower
      waist circumference in women also. Additionally, the CC genotype and/or C allele
      was associated with lower fasting glucose and insulin, and 30 and 120 min glucose
      in men (respectively, p = 0.08, 0.04, 0.01, 0.06). Lower means of systolic blood
      pressure, pulse pressure, cholesterol, and fasting triglyceride were also
      observed for the CC genotype in both genders though these were not statistically
      significant. CONCLUSIONS: The AGTR1 1166 CC genotype appears to predispose to
      favourable anthropometric and metabolic traits, relative to cardiovascular risk.

PMID- 15863670
TI  - A new syndrome, congenital extraocular muscle fibrosis with ulnar hand anomalies,
      maps to chromosome 21qter.
AB  - BACKGROUND: Congenital fibrosis of the extraocular muscles (CFEOM) is a
      heterogeneous group of disorders that may be associated with other anomalies. The
      association of a CFEOM syndrome with ulnar hand abnormalities (CFEOM/U) has not
      been reported to date. OBJECTIVE: To describe a new autosomal recessive syndrome
      of CFEOM and ulnar hand abnormalities, and localise the disease causing gene.
      METHODS: Clinical evaluation of the affected members and positional mapping.
      RESULTS: Six affected patients with CFEOM/U (aged 2 to 29 years) from a large
      consanguineous Turkish family were studied. Ophthalmological involvement was
      characterised by non-progressive restrictive ophthalmoplegia with blepharoptosis
      of the right eye. The postaxial oligodactyly/oligosyndactyly of the hands was
      more severe on the right side. A genome-wide scan established linkage of this new
      autosomal recessive syndrome to a locus on chromosome 21qter. The multipoint LOD
      score was 4.53 at microsatellite marker D21S1259, and fine mapping defined a
      approximately 1.5 Mb critical region between microsatellite marker D21S1897 and
      the telomere of the long arm. CONCLUSIONS: CFEOM/U maps to a 1.5 Mb region at
      chromosome 21qter. Future identification of the disease causing gene may provide
      insights into the development of the extraocular muscles and brain stem alpha
      motor neurones, as well as anteroposterior limb development.

PMID- 15863669
TI  - Evidence of an association between genetic variation of the coactivator PGC-1beta
      and obesity.
AB  - BACKGROUND: Peroxisome proliferator activated receptor-gamma coactivator-1beta
      (PGC-1beta) is a recently identified homologue of the tissue specific coactivator
      PGC-1alpha, a coactivator of transcription factors such as the peroxisome
      proliferators activated receptors and nuclear respiratory factors. PGC-1alpha is
      involved in adipogenesis, mitochondrial biogenesis, fatty acid beta oxidation,
      and hepatic gluconeogenesis. METHODS: We studied variation in the coding region
      of human PPARGC1B in Danish whites and related these variations to the prevalence
      of obesity and type 2 diabetes in population based samples. RESULTS: Twenty
      nucleotide variants were identified. In a study of 525 glucose tolerant subjects,
      the Ala203Pro and Val279Ile variants were in almost complete linkage
      disequilibrium (R2 = 0.958). In a case-control study of obesity involving a total
      of 7790 subjects, the 203Pro allele was significantly less frequent among obese
      participants (p = 0.004; minor allele frequencies: normal weight subjects 8.1%
      (95% confidence interval: 7.5 to 8.8), overweight subjects 7.6% (7.0 to 8.3),
      obese subjects 6.5% (5.6 to 7.3)). In a case-control study involving 1433
      patients with type 2 diabetes and 4935 glucose tolerant control subjects, none of
      the examined variants were associated with type 2 diabetes. CONCLUSIONS:
      Variation of PGC-1beta may contribute to the pathogenesis of obesity, with a
      widespread Ala203 allele being a risk factor for the development of this common
      disorder.

PMID- 15863671
TI  - Identification of discrete chromosomal deletion by binary recursive partitioning
      of microarray differential expression data.
AB  - DNA copy number abnormalities (CNA) are characteristic of tumours, and are also
      found in association with congenital anomalies and mental retardation. The
      ultimate impact of copy number abnormalities is manifested by the altered
      expression of the encoded genes. We previously developed a statistical method for
      the detection of simple chromosomal amplification using microarray expression
      data. In this study, we significantly advanced those analytical techniques to
      allow detection of localised chromosomal deletions based on differential gene
      expression data. Using three cell lines with known chromosomal deletions as model
      system, mRNA expression in those cells was compared with that observed in diploid
      cell lines of matched tissue origin. Results show that genes from deleted
      chromosomal regions are substantially over-represented (p<0.000001 by chi2) among
      genes identified as underexpressed in deletion cell lines relative to normal
      matching cells. Using a likelihood based statistical model, we were able to
      identify the breakpoint of the chromosomal deletion and match with the karyotype
      data in each cell line. In one such cell line, our analyses refined a previously
      identified 10p chromosomal deletion region. The deletion region was mapped to
      between 10p14 and 10p12, which was further confirmed by subtelomeric fluorescence
      in situ hybridisation. These data show that microarray differential expression
      data can be used to detect and map the boundaries of submicroscopic chromosomal
      deletions.

PMID- 15863672
TI  - Variability of sexual phenotype in 46,XX(SRY+) patients: the influence of
      spreading X inactivation versus position effects.

PMID- 15863673
TI  - STK11 genotyping and cancer risk in Peutz-Jeghers syndrome.

PMID- 15863674
TI  - Novel association of RP1 gene mutations with autosomal recessive retinitis
      pigmentosa.

PMID- 15863675
TI  - Protective and susceptibility effects of hSKCa3 allelic variants on juvenile
      myoclonic epilepsy.

PMID- 15863676
TI  - Identification of a novel mutation disrupting the DNA binding activity of GCM2 in
      autosomal recessive familial isolated hypoparathyroidism.

PMID- 15863677
TI  - Knowledge commons or economic engine--what's a university for?

PMID- 15863678
TI  - Methodological quality and reporting of ethical requirements in phase III cancer
      trials.
AB  - BACKGROUND: The approval of a research ethics committee (REC) and obtaining
      informed consent from patients (ICP) could be considered the main issues in the
      ethics of research with human beings. The aim of this study was to assess both
      methodological quality and ethical quality, and also to assess the relationship
      between these two qualities in randomised phase III cancer trials. METHOD:
      Methodological quality (Jadad score) and ethical quality (Berdeu score) were
      assessed for all randomised controlled trials (RCTs) published in 10
      international journals between 1999 and 2001 (n = 231). RESULTS: The mean Jadad
      score was 9.86 +/- 1.117. The methodological quality was poor in 75 RCTs (Jadad
      score <9). The mean Berdeu score was 0.42 +/- 0.133. The mean ethical quality
      score for poor methodological quality RCTs (n = 75) was 0.39 +/- 0.133; it was
      0.43 +/- 0.133 for good (n = 156) methodological quality RCTs (p = 0.07). There
      was improvement in ethical quality according to the year of commencement of the
      trials (p < 0.001). There was no correlation between methodological quality and
      the number of participating patients (R2 = 0.003, p = 0.78), between ethical
      quality and the number of participating patients (R2 = 0.003, p = 0.76 ), or
      between ethical quality and methodological quality (R2 = 0.012, p = 0.1). ICP and
      REC approval were not obtained for 21 and 77 trials respectively. CONCLUSION: The
      association between methodological quality and the reporting of ethical
      requirements probably reflects the respect shown for patients during the whole
      research process. These results suggest that closer attention to the conduct of
      clinical research, as well as the reporting of its ethical aspects, is needed.

PMID- 15863679
TI  - Clinical bioethics integration, sustainability, and accountability: the Hub and
      Spokes Strategy.
AB  - The "lone" clinical bioethicist working in a large, multisite hospital faces
      considerable challenges. While attempting to build ethics capacity and sustain a
      demanding range of responsibilities, he or she must also achieve an acceptable
      level of integration, sustainability, and accountability within a complex
      organisational structure. In an effort to address such inherent demands and to
      create a platform towards better evaluation and effectiveness, the Clinical
      Ethics Group at the Joint Centre for Bioethics at the University of Toronto is
      implementing the Hub and Spokes Strategy at seven hospitals. The goal of the Hub
      and Spokes Strategy is to foster an ethical climate and strengthen ethics
      capacity broadly throughout healthcare settings as well as create models in
      clinical bioethics that are excellent and effective.

PMID- 15863681
TI  - Should doctors talk to relatives without a competent patient's consent?
AB  - A view from a student: ethical teaching, based on ethical guidelines, is at odds
      with clinical practice. Is this poor practice, or is the ethical guidance too
      simple?

PMID- 15863680
TI  - "I can put the medicine in his soup, Doctor!".
AB  - The practice of covertly administering medication is controversial. Although
      condemned by some as overly paternalistic, others have suggested that it may be
      acceptable if patients have permanent mental incapacity and refuse needed
      treatment. Ethical, legal, and clinical considerations become more complex when
      the mental incapacity is temporary and when the medication actually serves to
      restore autonomy. We discuss these issues in the context of a young man with
      schizophrenia. His mother had been giving him antipsychotic medication covertly
      in his soup. Should the doctor continue to provide a prescription, thus allowing
      this to continue? We discuss this case based on the "four principles" ethical
      framework, addressing the conflict between autonomy and beneficence/non
      maleficence, the role of antipsychotics as an autonomy restoring agent, truth
      telling and the balance between individual versus family autonomy.

PMID- 15863682
TI  - The winner takes it all.

PMID- 15863683
TI  - Off-label administration of drugs to healthy military personnel. Dubious ethics
      of preventive measures.

PMID- 15863684
TI  - The search for organs: halachic perspectives on altruistic giving and the selling
      of organs.
AB  - Altruistic donation of organs from living donors is widely accepted as a virtue
      and even encouraged as a duty. Selling organs, on the other hand, is highly
      controversial and banned in most countries. What is the Jewish legal (halachic)
      position on these issues? In this review it is explained that altruistic donation
      is praiseworthy but in no way obligatory. Selling organs is a subject of rabbinic
      dispute among contemporary authorities.

PMID- 15863685
TI  - The fable of the dragon tyrant.
AB  - This paper recounts the tale of a most vicious dragon that ate thousands of
      people every day, and of the actions that the king, the people, and an assembly
      of dragonologists took with respect thereof.

PMID- 15863686
TI  - The book of life.
AB  - It has recently been suggested that the practice of bioethics in the area of
      biology and genetics has been hampered by the lack of an accurate and appropriate
      metaphor. Beginning with previous metaphors that have compared the genome with a
      static blueprint or "book of life", I develop a dynamic metaphor that is
      compatible with our present understanding of the role of genetics in biology. The
      resulting metaphor is not only an accurate representation of current biology but
      of particular use to bioethicists and non-biologists in general.

PMID- 15863687
TI  - Assisted reproductive technologies and equity of access issues.
AB  - In Australia and other countries, certain groups of women have traditionally been
      denied access to assisted reproductive technologies (ARTs). These typically are
      single heterosexual women, lesbians, poor women, and those whose ability to rear
      children is questioned, particularly women with certain disabilities or who are
      older. The arguments used to justify selection of women for ARTs are most often
      based on issues such as scarcity of resources, and absence of infertility (in
      lesbians and single women), or on social concerns: that it "goes against nature";
      particular women might not make good mothers; unconventional families are not
      socially acceptable; or that children of older mothers might be orphaned at an
      early age. The social, medical, legal, and ethical reasoning that has
      traditionally promoted this lack of equity in access to ARTs, and whether the
      criteria used for client deselection are ethically appropriate in any particular
      case, are explored by this review. In addition, the issues of distribution and
      just "gatekeeping" practices associated with these sensitive medical services are
      examined.

PMID- 15863688
TI  - No sex selection please, we're British.

PMID- 15863689
TI  - Reproductive liberty and elitist contempt: reply to John Harris.

PMID- 15863690
TI  - Sex selection and regulated hatred.
AB  - This paper argues that the HFEA's recent report on sex selection abdicates its
      responsibility to give its own authentic advice on the matters within its remit,
      that it accepts arguments and conclusions that are implausible on the face of it
      and where they depend on empirical claims, produces no empirical evidence
      whatsoever, but relies on reckless speculation as to what the "facts" are likely
      to be. Finally, having committed itself to what I call the "democratic
      presumption", that human freedom will not be constrained unless very good and
      powerful reasons can be produced to justify such infringement of liberty, the
      HFEA simply reformulates the democratic presumption as saying the opposite-
      namely that freedom may only be exercised if powerful justifications are produced
      for any exercise of liberty.

PMID- 15863692
TI  - Capabilities and health.
AB  - Sen's capabilities approach offers a radical generalisation of the conventional
      approach to welfare economics. It has been highly influential in development and
      many researchers are now beginning to explore its implications for health care.
      This paper contributes to the emerging debate by discussing two examples of such
      applications: first, at the individual decision making level, namely the right to
      die, and second, at the social choice level. For the first application, which
      draws on Nussbaum's list of capabilities, it is argued that many capabilities are
      ambiguously or indirectly related to the right to die, but the ability to form a
      concept of the good life and plan one's own life provides a direct justification
      for such a right. In the second application, the focus is specifically on
      healthcare rationing and it is argued that, although not committed to age based
      rationing, the capabilities approach provides a more natural justification of age
      related access to health care than the fair innings argument, which is often used
      to justify the alleged ageism inherent in quality adjusted life years (QALY)
      maximisation.

PMID- 15863691
TI  - Gender, ageing, and injustice: social and political contexts of bioethics.
AB  - There has been considerable work in bioethics addressing injustice and gender
      oppression in the provision of healthcare services, in the interaction between
      client and healthcare professional, and in allocation of healthcare services
      within a particular hospital or health service. There remain several sites of
      continued injustice that can only be addressed adequately from a broader
      analytical perspective, one that attends to the social and political contexts
      framing healthcare policy and practice. Feminist bioethicists have a strong track
      record in providing this kind of analysis. Using current Australian aged care and
      welfare policy this paper demonstrates some of the ways in which issues of
      gender, age, and social inequity shape bioethical debate, policy, and practice in
      the areas of aged care and welfare provision. The author develops an argument
      that demonstrates the gender injustice underlying health care and welfare policy.
      This argument recognises the inevitability of human dependency relations, and
      questions the adequacy of current political theories to address the requirements
      for full and equal citizenship. The author shows that an adequate analysis of the
      ethics of aged healthcare depends on sufficient consideration of the social and
      political context within which healthcare policy is framed and an adequate
      understanding of human dependency.

PMID- 15863693
TI  - High need patients receiving targeted entitlements: what responsibilities do they
      have in primary health care?
AB  - Patient responsibilities in primary health care are controversial and, by
      comparison, the responsibilities of high need patients are less clear. This paper
      aims to suggest why high need patients receiving targeted entitlements in primary
      health care are free to have prima facie special responsibilities; why, given
      this freedom, these patients morally have special responsibilities; what these
      responsibilities are, and how publicly funded health systems ought to be able to
      respond when these remain unmet. It is suggested that the special
      responsibilities and their place in public policy acquire moral significance as a
      means to discharge a moral debt, share special knowledge, and produce desirable
      consequences in regard to personal and collective interests. Special
      responsibilities magnify ordinary patient responsibilities and require patients
      not to hesitate regarding attendance for primary health care. Persistent patient
      disregard of special responsibilities may necessitate limiting the scope of these
      responsibilities, removing system barriers, or respecifying special rights.

PMID- 15863694
TI  - Do drug firms hoodwink medical journals? Or is something wrong with the
      contribution and integrity of declared authors?

PMID- 15863695
TI  - The scandal of unfair behaviour of senior faculty.

PMID- 15863696
TI  - Metabolism of the alpha,beta-unsaturated ketones, chalcone and trans-4-phenyl-3
      buten-2-one, by rat liver microsomes and estrogenic activity of the metabolites.
AB  - When chalcone and trans-4-phenyl-3-buten-2-one (PBO) were incubated with liver
      microsomes of untreated rats in the presence of NADPH, 4-hydroxychalcone and
      trans-4-(4-hydroxyphenyl)-3-buten-2-one (4-OH-PBO), respectively, were formed as
      major metabolites. Two minor metabolites of chalcone, 4'-hydroxychalcone and 2
      hydroxychalcone, were also observed. The oxidase activity affording 4
      hydroxychalcone was inhibited by SKF 525-A, disulfiram, ketoconazole, and alpha
      naphthoflavone. The oxidase activities leading to 4-hydroxychalcone and 4'
      hydroxychalcone were enhanced in liver microsomes of 3-methylcholanthrene- and
      phenobarbital-treated rats, respectively. The activity generating 2
      hydroxychalcone was enhanced in liver microsomes of 3-methylcholanthrene- and
      dexamethasone-treated rats. The oxidation of PBO to 4-OH-PBO was inhibited by SKF
      525-A, ketoconazole, disulfiram, and sulfaphenazole. This activity was enhanced
      in liver microsomes of 3-methylcholanthrene-, acetone- and phenobarbital-treated
      rats. 4-Hydroxylation, 4'-hydroxylation, and 2-hydroxylation of chalcone were
      catalyzed by rat recombinant cytochrome P450 1A1, 1A2, and 2C6; by 1A1 and 2C6;
      and by 1A1 and 3A1, respectively. PBO was oxidized by cytochrome P450 1A1, 1A2,
      2C6, and 2E1. Chalcone and PBO were negative in an estrogen reporter assay using
      estrogen-responsive human breast cancer cell line MCF-7. However, 4
      hydroxychalcone, 2-hydroxychalcone, 4'-hydroxychalcone, and 4-OH-PBO exhibited
      estrogenic activity.

PMID- 15863697
TI  - Immobilization of aluminum with phosphorus in roots is associated with high
      aluminum resistance in buckwheat.
AB  - Oxalic acid secretion from roots is considered to be an important mechanism for
      aluminum (Al) resistance in buckwheat (Fygopyrum esculentum Moench). Nonetheless,
      only a single Al-resistant buckwheat cultivar was used to investigate the
      significance of oxalic acid in detoxifying Al. In this study, we investigated two
      buckwheat cultivars, Jiangxi (Al resistant) and Shanxi (Al sensitive), which
      showed significant variation in their resistance to Al stress. In the presence of
      0 to 100 microM Al, the inhibition of root elongation was greater in Shanxi than
      that in Jiangxi, and the Al content of root apices (0-10 mm) was much lower in
      Jiangxi. However, the dependence of oxalic acid secretion on external Al
      concentration and the time course for secretion were similar in both cultivars.
      Furthermore, the variation in Al-induced oxalic acid efflux along the root was
      similar, showing a 10-fold greater efflux from the apical 0- to 5-mm region than
      from the 5- to 10-mm region. These results suggest that both Shanxi and Jiangxi
      possess an equal capacity for Al-dependent oxalic acid secretion. Another two
      potential Al resistance mechanisms, i.e. Al-induced alkalinization of rhizosphere
      pH and root inorganic phosphate release, were also not involved in their
      differential Al resistance. However, after longer treatments in Al (10 d), the
      concentrations of phosphorus and Al in the roots of the Al-resistant cultivar
      Jiangxi were significantly higher than those in Shanxi. Furthermore, more Al was
      localized in the cell walls of the resistant cultivar. All these results suggest
      that while Al-dependent oxalic acid secretion might contribute to the overall
      high resistance to Al stress of buckwheat, this response cannot explain the
      variation in tolerance between these two cultivars. We present evidence
      suggesting the greater Al resistance in buckwheat is further related to the
      immobilization and detoxification of Al by phosphorus in the root tissues.

PMID- 15863698
TI  - The Arabidopsis IspH homolog is involved in the plastid nonmevalonate pathway of
      isoprenoid biosynthesis.
AB  - Plant isoprenoids are synthesized via two independent pathways, the cytosolic
      mevalonate (MVA) pathway and the plastid nonmevalonate pathway. The Escherichia
      coli IspH (LytB) protein is involved in the last step of the nonmevalonate
      pathway. We have isolated an Arabidopsis (Arabidopsis thaliana) ispH null mutant
      that has an albino phenotype and have generated Arabidopsis transgenic lines
      showing various albino patterns caused by IspH transgene-induced gene silencing.
      The initiation of albino phenotypes rendered by IspH gene silencing can arise
      independently from multiple sites of the same plant. After a spontaneous
      initiation, the albino phenotype is systemically spread toward younger tissues
      along the source-to-sink flow relative to the initiation site. The development of
      chloroplasts is severely impaired in the IspH-deficient albino tissues. Instead
      of thylakoids, mutant chloroplasts are filled with vesicles. Immunoblot analysis
      reveals that Arabidopsis IspH is a chloroplast stromal protein. Expression of
      Arabidopsis IspH complements the lethal phenotype of an E. coli ispH mutant. In 2
      week-old Arabidopsis seedlings, the expression of 1-deoxy-d-xylulose 5-phosphate
      synthase (DXS), 1-deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), IspD,
      IspE, IspF, and IspG genes is induced by light, whereas the expression of the
      IspH gene is constitutive. The addition of 3% sucrose in the media slightly
      increased levels of DXS, DXR, IspD, IspE, and IspF mRNA in the dark. In a 16-h
      light/8-h-dark photoperiod, the accumulation of the IspH transcript oscillates
      with the highest levels detected in the early light period (2-6 h) and the late
      dark period (4-6 h). The expression patterns of DXS and IspG are similar to that
      of IspH, indicating that these genes are coordinately regulated in Arabidopsis
      when grown in a 16-h-light/8-h-dark photoperiod.

PMID- 15863699
TI  - Transcriptional profiling of sorghum induced by methyl jasmonate, salicylic acid,
      and aminocyclopropane carboxylic acid reveals cooperative regulation and novel
      gene responses.
AB  - We have conducted a large-scale study of gene expression in the C4 monocot
      sorghum (Sorghum bicolor) L. Moench cv BTx623 in response to the signaling
      compounds salicylic acid (SA), methyl jasmonate (MeJA), and the ethylene
      precursor aminocyclopropane carboxylic acid. Expression profiles were generated
      from seedling root and shoot tissue at 3 and 27 h, using a microarray containing
      12,982 nonredundant elements. Data from 102 slides and quantitative reverse
      transcription-PCR data on mRNA abundance from 171 genes were collected and
      analyzed and are here made publicly available. Numerous gene clusters were
      identified in which expression was correlated with particular signaling compound
      and tissue combinations. Many genes previously implicated in defense responded to
      the treatments, including numerous pathogenesis-related genes and most members of
      the phenylpropanoid pathway, and several other genes that may represent novel
      activities or pathways. Genes of the octadecanoic acid pathway of jasmonic acid
      (JA) synthesis were induced by SA as well as by MeJA. The resulting hypothesis
      that increased SA could lead to increased endogenous JA production was confirmed
      by measurement of JA content. Comparison of responses to SA, MeJA, and combined
      SA+MeJA revealed patterns of one-way and mutual antagonisms, as well as
      synergistic effects on regulation of some genes. These experiments thus help
      further define the transcriptional results of cross talk between the SA and JA
      pathways and suggest that a subset of genes coregulated by SA and JA may comprise
      a uniquely evolved sector of plant signaling responsive cascades.

PMID- 15863700
TI  - Molecular and biochemical characterization of the selenocysteine Se
      methyltransferase gene and Se-methylselenocysteine synthesis in broccoli.
AB  - Selenium (Se) plays an indispensable role in human nutrition and has been
      implicated to have important health benefits, including being a cancer
      preventative agent. While different forms of Se vary in their anticarcinogenic
      efficacy, Se-methylselenocysteine (SeMSC) has been demonstrated to be one of the
      most effective chemopreventative compounds. Broccoli (Brassica oleracea var.
      italica) is known for its ability to accumulate high levels of Se with the
      majority of the selenoamino acids in the form of Se-methylselenocysteine.
      Therefore, it serves as a good model to study the regulation of SeMSC
      accumulation in plants. A cDNA encoding selenocysteine Se-methyltransferase, the
      key enzyme responsible for SeMSC formation, was cloned from broccoli using a
      homocysteine S-methyltransferase gene probe from Arabidopsis (Arabidopsis
      thaliana). This clone, designated as BoSMT, was functionally expressed in
      Escherichia coli, and its identity was confirmed by its substrate specificity in
      the methylation of selenocysteine. The BoSMT gene represents a single copy
      sequence in the broccoli genome. Examination of BoSMT gene expression and SeMSC
      accumulation in response to selenate, selenite, and sulfate treatments showed
      that the BoSMT transcript and SeMSC synthesis were significantly up-regulated in
      plants exposed to selenate but were low in plants supplied with selenite.
      Simultaneous treatment of selenate with selenite significantly reduced SeMSC
      production. In addition, high levels of sulfate suppressed selenate uptake,
      resulting in a dramatic reduction of BoSMT mRNA level and SeMSC accumulation. Our
      results reveal that SeMSC accumulation closely correlated with the BoSMT gene
      expression and the total Se status in tissues and provide important information
      for maximizing the SeMSC production in this beneficial vegetable plant.

PMID- 15863701
TI  - Increased sedoheptulose-1,7-bisphosphatase activity in transgenic tobacco plants
      stimulates photosynthesis and growth from an early stage in development.
AB  - Activity of the Calvin cycle enzyme sedoheptulose-1,7-bisphosphatase (SBPase) was
      increased by overexpression of an Arabidopsis (Arabidopsis thaliana) cDNA in
      tobacco (Nicotiana tabacum) plants. In plants with increased SBPase activity,
      photosynthetic rates were increased, higher levels of Suc and starch accumulated
      during the photoperiod, and an increase in leaf area and biomass of up to 30% was
      also evident. Light saturated photosynthesis increased with increasing SBPase
      activity and analysis of CO2 response curves revealed that this increase in
      photosynthesis could be attributed to an increase in ribulose 1,5-bisphosphate
      regenerative capacity. Seedlings with increased SBPase activity had an increased
      leaf area at the 4 to 5 leaf stage when compared to wild-type plants, and
      chlorophyll fluorescence imaging of these young plants revealed a higher
      photosynthetic capacity at the whole plant level. Measurements of photosynthesis,
      made under growth conditions integrated over the day, showed that mature plants
      with increased SBPase activity fixed 6% to 12% more carbon than equivalent wild
      type leaves, with the young leaves having the highest rates. In this paper, we
      have shown that photosynthetic capacity per unit area and plant yield can be
      increased by overexpressing a single native plant enzyme, SBPase, and that this
      gives an advantage to the growth of these plants from an early phase of
      vegetative growth. This work has also shown that it is not necessary to bypass
      the normal regulatory control of SBPase, exerted by conditions in the stroma, to
      achieve improvements in carbon fixation.

PMID- 15863702
TI  - Genome-wide analysis of gene expression profiles associated with cell cycle
      transitions in growing organs of Arabidopsis.
AB  - Organ growth results from the progression of component cells through subsequent
      phases of proliferation and expansion before reaching maturity. We combined
      kinematic analysis, flowcytometry, and microarray analysis to characterize cell
      cycle regulation during the growth process of leaves 1 and 2 of Arabidopsis
      (Arabidopsis thaliana). Kinematic analysis showed that the epidermis proliferates
      until day 12; thereafter, cells expand until day 19 when leaves reach maturity.
      Flowcytometry revealed that endoreduplication occurs from the time cell division
      rates decline until the end of cell expansion. Analysis of 10 time points with a
      6k-cDNA microarray showed that transitions between the growth stages were closely
      reflected in the mRNA expression data. Subsequent genome-wide microarray analysis
      on the three main stages allowed us to categorize known cell cycle genes into
      three major classes: constitutively expressed, proliferative, and inhibitory.
      Comparison with published expression data obtained from root zones corresponding
      to similar developmental stages and from synchronized cell cultures supported
      this categorization and enabled us to identify a high confidence set of 131
      proliferation genes. Most of those had an M phase-dependent expression pattern
      and, in addition to many known cell cycle-related genes, there were at least 90
      that were unknown or previously not associated with proliferation.

PMID- 15863703
TI  - Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation
      in the mouse.
AB  - Hydrogen sulfide (H2S) is synthesized in the body from L-cysteine by several
      enzymes including cystathionine-gamma-lyase (CSE). To date, there is little
      information about the potential role of H2S in inflammation. We have now
      investigated the part played by H2S in endotoxin-induced inflammation in the
      mouse. E. coli lipopolysaccharide (LPS) administration produced a dose (10 and 20
      mg/kg ip)- and time (6 and 24 h)-dependent increase in plasma H2S concentration.
      LPS (10 mg/kg ip, 6 h) increased plasma H2S concentration from 34.1 +/- 0.7
      microM to 40.9 +/- 0.6 microM (n=6, P<0.05) while H2S formation from added L
      cysteine was increased in both liver and kidney. CSE gene expression was also
      increased in both liver (94.2+/-2.7%, n=6, P<0.05) and kidney (77.5+/-3.2%, n=6,
      P<0.05). LPS injection also elevated lung (148.2+/-2.6%, n=6, P<0.05) and kidney
      (78.8+/-8.2%, n=6, P<0.05) myeloperoxidase (MPO, a marker of tissue neutrophil
      infiltration) activity alongside histological evidence of lung, liver, and kidney
      tissue inflammatory damage. Plasma nitrate/nitrite (NOx) concentration was
      additionally elevated in a time- and dose-dependent manner in LPS-injected
      animals. To examine directly the possible proinflammatory effect of H2S, mice
      were administered sodium hydrosulfide (H2S donor drug, 14 micromol/kg ip) that
      resulted in marked histological signs of lung inflammation, increased lung and
      liver MPO activity, and raised plasma TNF-alpha concentration (4.6+/-1.4 ng/ml,
      n=6). In contrast, DL-propargylglycine (CSE inhibitor, 50 mg/kg ip), exhibited
      marked anti-inflammatory activity as evidenced by reduced lung and liver MPO
      activity, and ameliorated lung and liver tissue damage. In separate experiments,
      we also detected significantly higher (150.5+/-43.7 microM c.f. 43.8+/-5.1
      microM, n=5, P<0.05) plasma H2S levels in humans with septic shock. These
      findings suggest that H2S exhibits proinflammatory activity in endotoxic shock
      and suggest a new approach to the development of novel drugs for this condition.

PMID- 15863704
TI  - Research on environmental effects in genetic studies of aging: introduction.

PMID- 15863705
TI  - Research on environmental effects in genetic studies of aging: comments.

PMID- 15863706
TI  - Social environments and the genetics of aging: advancing knowledge of protective
      health mechanisms.
AB  - We selectively review the literature in behavioral and molecular genetics,
      including both laboratory and epidemiologic studies, with emphasis on how social
      environments, particularly emotion in significant social relationships, influence
      gene expression. Attention is given to cross-talk between human and animal
      studies. Environments are pivotal in understanding phenotypic outcomes, and this
      demands research on gene-environment interactions. Illustrative interactions,
      involving both behavioral and molecular genetics, are provided. Many people with
      susceptibility genes for diverse diseases never proceed to disease status.
      Substantial associational evidence implicates social environmental factors as
      protective agents. Mechanistic understanding of these linkages is quite advanced
      in some animal populations and suggests new lines of inquiry in human studies.
      Developing the interface between genetics, social environments, and health will
      require close collaboration between those well versed in molecular biology and
      biochemistry and persons with expertise in genetic epidemiology and social
      psychology. Particularly important is the identification of environmental
      influences that protect susceptible persons from disease incidence.

PMID- 15863707
TI  - Cognitive change in aging: identifying gene-environment correlation and nonshared
      environment mechanisms.
AB  - We describe gene-environment processes that may help account for individual
      differences in successful aging. Our emphasis is on successful aging in the
      cognitive domain, wherein individuals come to use a variety of strategies to cope
      with changes in cognitive capacities. We focus on the role of executive control
      in particular and define gene-environment correlation and nonshared environmental
      mechanisms. The quantitative genetic methods used to identify these mechanisms
      are described, with examples from research in childhood, where such studies are
      now common. Future work will be most effective if it is guided by life-span
      development frameworks that address these processes, such as the developmental
      genotype-->environment theory of Scarr and McCartney and the
      selection/optimization/compensation theory of Baltes and Baltes.

PMID- 15863708
TI  - Mammary cancer and social interactions: identifying multiple environments that
      regulate gene expression throughout the life span.
AB  - Now that the human genome has been sequenced, along with those of major animal
      models, there is an urgent need to define those environments that interact with
      genes. The traditional view focuses on ways that gene products interact with the
      nuclear environment to regulate cell function, causing the physiologic changes,
      behaviors, and diseases manifest throughout development and aging. Although this
      view is essential, it is equally essential to understand the converse
      relationship, namely, to identify those environments at higher levels of
      organization that regulate the expression of specific genes. Given the vastness
      of this problem, one effective strategy is to start with a trait for which some
      of the genes have already been identified, such as malignant disease. In rats,
      social isolation and hypervigilance increase the incidence of mammary tumors,
      accelerate aging, and shorten the life span. We propose that similar
      environmental regulation of gene expression may underlie the disproportionately
      high mortality from premenopausal breast cancer of Blacks, a minority group that
      can experience high levels of loneliness and hypervigilance. Our goal is to
      identify which environments-social, psychological, hormonal, and cellular
      regulate genetic mechanisms of mammary cancer risk as well as the specific times
      in the life span when they do so.

PMID- 15863709
TI  - Predictors of physical health: toward an integrated model of genetic and
      environmental antecedents.
AB  - People in higher-income groups tend to experience better physical health, yet
      this does not appear to be the direct result of access to medical care. This has
      prompted a search for psychological factors more likely to be present in high
      income environments that might help to explain the relationship. Physical health
      has been associated with a number of such psychological measures including
      positive affect and well-being, negative affect and neuroticism, positive social
      relationships, and perceived control. Building from recent findings of moderation
      of genetic variance in physical health by income and perceived control, we
      explore the genetic and environmental relationships among all these variables in
      a nationwide U.S. twin sample. These relationships suggest possible mechanisms by
      which psychological characteristics, behaviors, physical health, and
      environmental circumstances could be influenced by common groups of genes with
      varying degrees of activity in different environments. We discuss the
      implications of such mechanisms for differential expression of genetic variation
      in the population and suggest ways in which consideration of such effects can
      inform gerontology research.

PMID- 15863710
TI  - The inherent complexities of gene-environment interactions.
AB  - The article outlines the complexities of gene-environment interactions in the
      determination of human disease, especially as they relate to aging, and stresses
      the importance of continuing such studies, in spite of their inherent
      difficulties. First, a capsule review of the literature pertaining to studies of
      gene-environment interactions is presented, and designs and methodologies used to
      detect these interactions are briefly discussed. Second, research questions and
      problems that can be addressed as outcomes of gene-environment interaction
      studies are exemplified. Third, a number of illustrative examples of gene
      environment interactions are presented. Fourth, various types of gene-environment
      interactions are briefly discussed. Fifth, concluding remarks are offered, and
      possibilities of studying gene-environment interaction within social and
      biological research on aging are outlined.

PMID- 15863711
TI  - Social context in gene-environment interactions: retrospect and prospect.
AB  - While many behavioral scientists believe that gene-environment (GE) interactions
      play an important and perhaps pervasive role in human development and aging,
      little attention has been devoted to a fundamental conceptual issue: What is it
      about social context that could alter gene expression? We draw on existing
      examples of GE interactions to formulate a typology that identifies a set of
      generic mechanisms by which E moderates G. Empirical studies suggest four ideal
      types: Social context can trigger a genetic diathesis, compensate for a genetic
      diathesis, act as a control to prevent behaviors for which there is a genetic
      predisposition, and enhance adaptation through proximal processes. This typology
      highlights several problems, however, with prior empirical research, which may
      explain, in part, why so few GE interactions have actually been observed. These
      problems include inattention to the dynamic nature of social experience, the
      manifold, often-intercorrelated dimensions of social context ("EE interactions"),
      mediators that link social context and the genotype, and analytic models that
      examine GE interactions as processes that characterize individual development. In
      turn, these insights call for the integration of life course sociology and
      behavioral genetics to foster ways of studying genes, context, and aging.

PMID- 15863713
TI  - Lipopolysaccharide, toll-like receptors, and the immune contribution to
      atherosclerosis.

PMID- 15863714
TI  - Natural killer T cells in atherosclerosis.

PMID- 15863715
TI  - Vitamin D nutrition does not cause peripheral artery disease.

PMID- 15863716
TI  - P-selectin and blood coagulation: it's not only about inflammation any more.

PMID- 15863717
TI  - Soluble levels of receptor for advanced glycation endproducts (sRAGE) and
      coronary artery disease: the next C-reactive protein?

PMID- 15863718
TI  - FGFR1 and the bloodline of the vasculature.

PMID- 15863719
TI  - SOD isoforms and signaling in blood vessels: evidence for the importance of ROS
      compartmentalization.

PMID- 15863720
TI  - The union of vascular and metabolic actions of insulin in sickness and in health.

PMID- 15863721
TI  - Making up and breaking up: the tortuous ways of the vascular wall.

PMID- 15863722
TI  - Regulation of the human cyclin C gene via multiple vitamin D3-responsive regions
      in its promoter.
AB  - The candidate human tumor suppressor gene cyclin C is a primary target of the
      anti-proliferative hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], but
      binding sites for the 1alpha,25(OH)2D3 receptor (VDR), so-called 1alpha,25(OH)2D3
      response elements (VDREs), have not yet been identified in the promoter of this
      gene. We screened various cancer cell lines by quantitative PCR and found that
      the 1alpha,25(OH)2D3 inducibility of cyclin C mRNA expression, in relationship
      with the 24-hydroxylase (CYP24) gene, was best in MCF-7 human breast cancer
      cells. To characterize the molecular mechanisms, we analyzed 8.4 kb of the cyclin
      C promoter by using chromatin immunoprecipitation assays (ChIP) with antibodies
      against acetylated histone 4, VDR and its partner receptor, retinoid X receptor
      (RXR). The histone 4 acetylation status of all 23 investigated regions of the
      cyclin C promoter did not change significantly in response to 1alpha,25(OH)2D3,
      but four independent promoter regions showed a consistent, 1alpha,25(OH)2D3
      dependent association with VDR and RXR over a time period of 240 min. Combined in
      silico/in vitro screening identified in each of these promoter regions a VDRE and
      reporter gene assays confirmed their functionality. Moreover, re-ChIP assays
      monitored simultaneous association of VDR with RXR, coactivator, mediator and RNA
      polymerase II proteins on these regions. Since cyclin C protein is associated
      with those mediator complexes that display transcriptional repressive properties,
      this study contributes to the understanding of the downregulation of a number of
      secondary 1alpha,25(OH)2D3-responding genes.

PMID- 15863723
TI  - Cyclohexenyl nucleic acids: conformationally flexible oligonucleotides.
AB  - Cyclohexenyl nucleic acid (CeNA) is a nucleic acid mimic, where the (deoxy)ribose
      sugar has been replaced by cyclohexenyl moieties. In order to study the
      conformation of cyclohexenyl nucleosides by NMR, the HexRot program was developed
      to calculate conformations from scalar coupling constants of cyclohexenyl
      compounds, analogous to the methods applied for (deoxy)ribose nucleosides. The
      conformational equilibria and the values of the thermodynamic parameters are very
      similar between a cyclohexenyl nucleoside [energy difference between 2H3 (N-type)
      and 2H3 (S-type) is 1.8 kJ/mol and equilibrium occurs via the eastern hemisphere
      with a barrier of 10.9 kJ/mol] and a natural ribose nucleoside (energy difference
      between N-type and S-type is 2 kJ/mol and equilibrium occurs via the eastern
      hemisphere with a barrier of 4-20 kJ/mol). The flexibility of the cyclohexenyl
      nucleoside was demonstrated by the fast equilibrium between two conformational
      states that was observed in a CeNA-U monomer, combined with the 2H3 conformation
      of the cyclohexene moiety when incorporated into a Dickerson dodecamer and the
      2H3 conformation when incorporated in a d(5'-GCGT*GCG-3')/d(5'-CGCACGC-3')
      duplex, as determined by the NMR spectroscopy. This represents the first example
      of a synthetic nucleoside that adopts different conformations when incorporated
      in different double-stranded DNA sequences.

PMID- 15863725
TI  - Selenocysteine insertion directed by the 3'-UTR SECIS element in Escherichia
      coli.
AB  - Co-translational insertion of selenocysteine (Sec) into proteins in response to
      UGA codons is directed by selenocysteine insertion sequence (SECIS) elements. In
      known bacterial selenoprotein genes, SECIS elements are located in the coding
      regions immediately downstream of UGA codons. Here, we report that a distant
      SECIS element can also function in Sec insertion in bacteria provided that it is
      spatially close to the UGA codon. We expressed a mammalian phospholipid
      hydroperoxide glutathione peroxidase in Escherichia coli from a construct in
      which a natural E.coli SECIS element was located in the 3'-untranslated region
      (3'-UTR) and adjacent to a sequence complementary to the region downstream of the
      Sec UGA codon. Although the major readthrough event at the UGA codon was
      insertion of tryptophan, Sec was also incorporated and its insertion was
      dependent on the functional SECIS element in the UTR, base-pairing potential of
      the SECIS flanking region and the Sec UGA codon. These data provide important
      implications into evolution of SECIS elements and development of a system for
      heterologous expression of selenoproteins and show that in addition to the
      primary sequence arrangement between UGA codons and SECIS elements, their
      proximity within the tertiary structure can support Sec insertion in bacteria.

PMID- 15863724
TI  - Repair of cyclobutane pyrimidine dimers or dimethylsulfate damage in DNA is
      identical in normal or telomerase-immortalized human skin fibroblasts.
AB  - The progression of a normal cell to senescence in vivo and in vitro is
      accompanied by a reduction in the length of the telomeres, the chromosome capping
      segments at the end of each linkage group. However, overexpression of the reverse
      transcriptase subunit (HTERT) of the ribonucleoprotein telomerase restores
      telomere length and delays cellular senescence. Although some data exist in the
      literature with respect to survival, no molecular data have shown that DNA repair
      in telomerase-immortalized cells is normal. Several telomerase-immortalized human
      skin fibroblast cell lines were constructed from a primary human fibroblast cell
      line. The primary line and the telomerase-immortalized cell lines were treated
      with either ultraviolet (UV) radiation or dimethylsulfate (DMS). UV radiation
      principally produces cyclobutane pyrimidine dimers that are repaired by
      nucleotide excision repair, whereas DMS introduces mainly N-methylpurines
      repaired by base excision repair. Here, we show that repair of both types of
      damage in the telomerase-immortalized human skin fibroblast cell lines is
      identical to repair observed in normal skin fibroblasts. Thus, telomerase
      expression and consequent immortalization of skin fibroblasts do not alter
      nucleotide or base excision repair in human cells.

PMID- 15863727
TI  - "Hardship exception" is necessary.

PMID- 15863726
TI  - U1 small nuclear RNP from Trypanosoma brucei: a minimal U1 snRNA with unusual
      protein components.
AB  - Processing of primary transcripts in trypanosomes requires trans splicing and
      polyadenylation, and at least for the poly(A) polymerase gene, also internal cis
      splicing. The trypanosome U1 snRNA, which is most likely a cis-splicing specific
      component, is unusually short and has a relatively simple secondary structure.
      Here, we report the identification of three specific protein components of the
      Trypanosoma brucei U1 snRNP, based on mass spectrometry and confirmed by in vivo
      epitope tagging and in vitro RNA binding. Both T.brucei U1-70K and U1C are only
      distantly related to known counterparts from other eukaryotes. The T.brucei U1
      70K protein represents a minimal version of 70K, recognizing the first loop
      sequence of U1 snRNA with the same specificity as the mammalian protein. The
      trypanosome U1C-like protein interacts with 70K directly and binds the 5'
      terminal sequence of U1 snRNA. Surprisingly, instead of U1A we have identified a
      novel U1 snRNP-specific protein, TbU1-24K. U1-24K lacks a known RNA-binding motif
      and integrates in the U1 snRNP via interaction with U1-70K. These data result in
      a model of the trypanosome U1 snRNP, which deviates substantially from our
      classical view of the U1 particle and may reflect the special requirements for
      splicing of a small set of cis-introns in trypanosomes.

PMID- 15863728
TI  - Kudos on electronic-only COMLEX-USA.

PMID- 15863729
TI  - Faith versus evidence: the real question in osteopathic medicine?

PMID- 15863730
TI  - Still keeping the faith.

PMID- 15863731
TI  - Same as it ever was.

PMID- 15863732
TI  - Osteopathic medical training revisited: developing tomorrow's physicians.

PMID- 15863733
TI  - Manipulative treatment of carpal tunnel syndrome: biomechanical and osteopathic
      intervention to increase the length of the transverse carpal ligament: part 2.
      Effect of sex differences and manipulative "priming".
AB  - As a theoretical basis for treatment of carpal tunnel syndrome (CTS) and
      expanding upon part 1 of this study, the authors investigated the effects of
      static loading (weights) and dynamic loading (osteopathic manipulation [OM]) on
      20 cadaver limbs (10 male, 10 female). This larger study group allowed for
      comparative analysis of results by sex and reversal of sequencing for testing
      protocols. In static loading, 10-newton loads were applied to metal pins inserted
      into carpal bones. In dynamic loading, the OM maneuvers used were those currently
      used in clinical settings to treat patients with CTS. Transverse carpal ligament
      (TCL) response was observed by measuring changes in the width of the transverse
      carpal arch (TCA) with three-dimensional video analysis and precision calipers.
      Results demonstrated maximal TCL elongation of 13% (3.7 mm) with a residual
      elongation after recovery of 9% (2.6 mm) from weight loads in the female cadaver
      limbs, compared to less than 1 mm as noted in part 1, which used lower weight
      loads and combined results from both sexes. Favorable responses to all
      interventions were more significant among female cadaver limbs. Higher weight
      loads also caused more linear translatory motion through the metal pins,
      resulting in TCA widening equal to 63% of the increases occurring at skin level,
      compared to only 38% with lower loads. When OM was performed first, it led to
      greater widening of the TCA and lengthening of the TCL during the weight loading
      that followed. Both methods hold promise to favorably impact the course of
      management of CTS, particularly in women.

PMID- 15863734
TI  - Cholinesterase inhibitors in the treatment of dementia.
AB  - Dementia associated with probable Alzheimer's disease (AD) is one of the most
      common types of dementia. Patients with AD often have cholinergic deficits in
      association with the disease. The cholinesterase inhibitors donepezil
      hydrochloride, galantamine hydrobromide, and rivastigmine tartrate are the
      current mainstays of symptomatic treatment for patients with AD. In clinical
      trials for all three agents, beneficial effects on standard measures of cognitive
      and global function have been observed in patients with mild to moderate AD.
      Although none of the cholinesterase inhibitors has been approved for treatment of
      patients in advanced stages of AD, all three agents have had beneficial cognitive
      effects among patients with less severe forms of the disease. The author provides
      information on recommended dosing for all three medications, noting that
      cholinesterase inhibitors must be titrated carefully. When administered with
      caution, galantamine, rivastigmine, and donepezil are generally well-tolerated
      pharmacologic treatment options. The author notes that, after patients and their
      caregivers understand that no change in status is considered an "improvement" and
      a desirable clinical outcome for patients with AD, if no benefits are achieved
      with the use of one cholinesterase inhibitor, switching to another medication in
      this class might be beneficial. The author further suggests that the benefits
      found in cholinesterase inhibitors for patients with AD might also be applicable
      to patients with other types of dementia such as vascular dementia and dementia
      with Lewy bodies as cholinergic deficits have been reported in association with
      these types of dementia as well.

PMID- 15863737
TI  - Immigration and schizophrenia: the social causation hypothesis revisited.

PMID- 15863738
TI  - The beginning of the end for the Kraepelinian dichotomy.

PMID- 15863739
TI  - From 'obstetric complications' to a maternal-foetal origin hypothesis of mood
      disorder.

PMID- 15863740
TI  - Regional volume deviations of brain structure in schizophrenia and psychotic
      bipolar disorder: computational morphometry study.
AB  - BACKGROUND: It is unclear whether schizophrenia and psychotic bipolar disorder
      are associated with similar deviations of brain morphometry. AIMS: To assess
      volumetric abnormalities of grey and white matter throughout the entire brain in
      individuals with schizophrenia or with bipolar disorder compared with the same
      control group. METHOD: Brain scans were obtained by magnetic resonance imaging
      from 25 people with schizophrenia, 37 with bipolar disorder who had experienced
      psychotic symptoms and 52 healthy volunteers. Regional deviation in grey and
      white matter volume was assessed using computational morphometry. RESULTS:
      Individuals with schizophrenia had distributed grey matter deficit predominantly
      involving the fronto-temporal neocortex, medial temporal lobe, insula, thalamus
      and cerebellum, whereas those with bipolar disorder had no significant regions of
      grey matter abnormality. Both groups had anatomically overlapping white matter
      deficits in regions normally occupied by major longitudinal and interhemispheric
      tracts. CONCLUSIONS: Schizophrenia and psychotic bipolar disorder are associated
      with distinct grey matter deficits but anatomically coincident white matter
      abnormalities.

PMID- 15863741
TI  - Neuropsychological impairments in people with schizophrenia or bipolar disorder
      and their unaffected relatives.
AB  - BACKGROUND: Neuropsychological abnormalities in schizophrenia are well replicated
      and are present in unaffected relatives. Cognitive findings in bipolar disorder
      are less clearly established. AIMS: To examine the possibility that these
      abnormalities may provide a means by which the disorders might be separated and
      to clarify the associations of phenotypic expression and genetic liability.
      METHOD: A neuropsychological test battery was administered to 50 control
      participants, 74 patients and 76 unaffected relatives recruited for the study.
      Patients included those with schizophrenia from families affected by
      schizophrenia alone, those with bipolar disorder from families affected by
      bipolar disorder alone and those with bipolar disorder from families affected by
      both disorders. Unaffected relatives were also recruited. RESULTS: Current,
      verbal and premorbid IQ were impaired in people with schizophrenia and in their
      close relatives. Memory was impaired in all patient and relative groups.
      Psychomotor performance and performance IQ were impaired in patients, regardless
      of diagnosis. CONCLUSIONS: This study finds evidence that intellectual
      abnormalities are related to a genetic liability to schizophrenia. Abnormalities
      of memory appear to be related to an increased liability to psychosis in general.
      No impairment was specific to bipolar disorder.

PMID- 15863742
TI  - Pathogenesis of schizophrenia: a psychopathological perspective.
AB  - BACKGROUND: Despite interest in early treatment of schizophrenia, premorbid and
      prodromal symptomatology remain poorly delineated. AIMS: To compare pre-illness
      symptomatology in patients at high risk of schizophrenia who progress to illness
      with that of high-risk subjects who remain well and with normal controls. METHOD:
      Using Present State Examination (PSE) data, symptomatic scales were devised from
      participants of the Northwick Park Study of first-episode schizophrenia and
      scores were compared on the first and last PSEs of participants of the Edinburgh
      High Risk Study. RESULTS: At entry, when still well, high-risk individuals who
      subsequently became ill (mean time to diagnosis 929 days; s.e.=138 days) scored
      significantly higher on'situational anxiety', 'nervous tension', 'depression',
      'changed perception'and 'hallucinations'than those remaining well and normal
      controls, who did not differ. With illness onset, affective symptomatology
      remained high but essentially stable. CONCLUSIONS: In genetically predisposed
      individuals, affective and perceptual disorders are prominent before any
      behavioural or subjective change that usually characterises the shift to
      schizophrenic prodrome or active illness.

PMID- 15863743
TI  - The Danish National Schizophrenia Project: prospective, comparative longitudinal
      treatment study of first-episode psychosis.
AB  - BACKGROUND: First-episode psychosis intervention may improve the course and
      outcome of schizophrenic disorders. AIMS: To describe the Danish National
      Schizophrenia Project and to measure the outcome of two different forms of
      intervention after 1 year, compared with standard treatment. METHOD: A
      prospective, prospective, longitudinal, multicentre investigation included 562
      patients, consecutively referred over a 2-year period, with a first episode of
      psychosis. Patients were allocated to supportive psychodynamic psychotherapy as a
      supplement to treatment as usual, an integrated, assertive, psychosocial and
      educational treatment programme or treatment as usual. RESULTS: There was a non
      significant tendency towards greater improvement in social functioning in the
      integrated treatment group and the supportive psychodynamic psychotherapy group
      compared with the treatment as usual group. Significance was reached for some
      measures when the confounding effect of drug and alcohol misuse was included.
      CONCLUSIONS: Integrated treatment and supportive psychodynamic psychotherapy in
      addition to treatment as usual may improve outcome after 1 year of treatment for
      people with first-episode psychosis, compared with treatment as usual alone.

PMID- 15863744
TI  - Birth dimensions and risk of depression in adulthood: cohort study of Danish men
      born in 1953.
AB  - BACKGROUND: Two British cohort studies have reported birth weight to be
      associated with self-reported depression in adulthood, even after adjustment for
      socio-economic factors. AIMS: To examine the relationship between birth
      dimensions and discharge from a psychiatric ward with a depression diagnosis in
      adulthood. METHOD: A cohort of 10 753 male singletons born in Copenhagen, Denmark
      in 1953 and for whom birth certificates had been traced in 1965 were followed
      from 1969 until 2002, with record linkage for date of first admission to a
      psychiatric ward that led to a discharge diagnosis of depression. RESULTS: A
      total of 190 men, corresponding to 1.8% of the cohort, had a discharge diagnosis
      of depression. The Cox's regression analyses failed to show any association
      between birth dimensions (birth weight and ponderal index) and risk of
      psychiatric ward diagnosis of depression in adult life, before or after
      adjustment for social indicators at birth. CONCLUSIONS: This study does not
      support the existence of a relation between birth dimensions and psychiatric ward
      admission for depression in adult men.

PMID- 15863745
TI  - Care staff training in detection of depression in residential homes for the
      elderly: randomised trial.
AB  - BACKGROUND: Many people with depression in residential care homes for the elderly
      do not receive treatment because their depression remains undetected. AIMS: To
      determine the effects of staff training on the detection, treatment and outcome
      of depression in residents of ten homes. METHOD: We conducted a randomised
      controlled trial in ten residential homes. The intervention consisted of a
      training programme for staff and collaborative evaluation by staff and a mental
      health specialist of residents with possible depression. RESULTS: Recognition of
      depression increased more in homes where staff received the training than in the
      control homes. Treatment rates also increased compared with control homes, but
      the increase was not significant. Residents with depressive symptoms had a more
      favourable course when staff had received training. Moreover, the prevalence of
      depressive symptoms decreased, but the decrease was not significant. CONCLUSIONS:
      Training of care staff results in the increased detection of depression in the
      elderly, a trend towards more treatment and better outcomes.

PMID- 15863746
TI  - Distinctive neurocognitive effects of repetitive transcranial magnetic
      stimulation and electroconvulsive therapy in major depression.
AB  - BACKGROUND: Studies have compared electroconvulsive therapy (ECT) and repetitive
      transcranial magnetic stimulation (rTMS) with regard to clinical efficacy in the
      treatment of depression, but no study has yet addressed the differential impact
      on cognition. AIMS: To compare the neurocognitive effects of unilateral ECT and
      rTMS. METHOD: Thirty patients with treatment-refractory non-psychotic major
      depression received an average of ten treatments with either unilateral ECT or
      left prefrontal rTMS and were assessed for objective and subjective cognitive
      impairments before and about a week after treatment. RESULTS: Treatment response
      was comparable (46% of the ECT group and 44% of the rTMS group showed a reduction
      of 50% or more in Hamilton Rating Scale for Depression scores). In patients
      treated with rTMS, cognitive performance remained constant or improved and memory
      complaints alleviated, whereas in the ECT group memory recall deficits emerged
      and memory complaints remained. CONCLUSIONS: In contrast to unilateral ECT, rTMS
      has no adverse memory effects.

PMID- 15863747
TI  - Mental health inequalities in Wales, UK: multi-level investigation of the effect
      of area deprivation.
AB  - BACKGROUND: Geographical variation in the prevalence of common mental disorders
      has not been explained adequately. AIMS: To investigate whether regional mental
      health differences in Wales would persist after having taken into account the
      characteristics of individuals and regional social deprivation. METHOD: Data from
      the 1998 Welsh Health Survey were used. Common mental disorders were assessed
      with the mental health index included in the Short-Form 36 health survey (SF-36).
      The data were analysed using a multi-level linear regression model. RESULTS: Of
      the total variance in the mental health index, 1.47% occurred at regional level
      (95% CI 0.56-2.38). Adjustment for individual characteristics did not explain the
      between-region variation. A higher area deprivation score was associated with a
      higher score on the mental health index. CONCLUSIONS: Mental health differences
      in Wales are partly explained by the level of regional social deprivation.

PMID- 15863748
TI  - Misdiagnosis of post-traumatic stress disorder following severe traumatic brain
      injury.
AB  - BACKGROUND: The incidence of post-traumatic stress disorder (PTSD) after
      traumatic brain injury is unclear. One issue involves the validity of diagnosis
      using self-report questionnaires. AIMS: To compare PTSD'caseness' arising from
      questionnaire self-report and structured interview. METHOD: Participants (n=34)
      with traumatic brain injury were recruited. Screening measures and self-report
      questionnaires were administered, followed by the structured interview. RESULTS:
      Using questionnaires, 59% fulfilled criteria for PTSD on the Post-traumatic
      Diagnostic Scale and 44% on the Impact of Events Scale, whereas using structured
      interview (Clinician-Administered PTSD Scale) only 3% were 'cases'. This
      discrepancy may arise from confusions between effects of PTSD and traumatic brain
      injury. CONCLUSIONS: After traumatic brain injury, PTSD self-report measures
      might be used for screening but not diagnosis.

PMID- 15863749
TI  - Psychological investigation of the structure of paranoia in a non-clinical
      population.
AB  - BACKGROUND: Previous studies of paranoia have assessed only limited numbers of
      paranoid thoughts, and have not considered the experience from a multidimensional
      perspective or examined the relationship between different suspicious thoughts.
      AIMS: To assess a wide range of paranoid thoughts multidimensionally and examine
      their distribution, to identify the associated coping strategies and to examine
      social-cognitive processes and paranoia. METHOD: Six questionnaire assessments
      were completed by 1202 individuals using the internet. RESULTS: Paranoid thoughts
      occurred regularly in approximately a third of the group. Increasing endorsement
      of paranoid thoughts was characterised by the recruitment of rarer and odder
      ideas. Higher levels of paranoia were associated with emotional and avoidant
      coping, less use of rational and detached coping, negative attitudes to emotional
      expression, submissive behaviours and lower social rank. CONCLUSIONS:
      Suspiciousness is common and there may be a hierarchical arrangement of such
      thoughts that builds on common emotional concerns.

PMID- 15863750
TI  - Community study of knowledge of and attitude to mental illness in Nigeria.
AB  - BACKGROUND: The improvement of community tolerance of people with mental illness
      is important for their integration. Little is known about the knowledge of and
      attitude to mental illness in sub-Saharan Africa. AIMS: To determine the
      knowledge and attitudes of a representative community sample in Nigeria. METHOD:
      A multistage, clustered sample of household respondents was studied in three
      states in the Yoruba-speaking parts of Nigeria (representing 22% of the national
      population). A total of 2040 individuals participated (responserate 74.2%).
      RESULTS: Poor knowledge of causation was common. Negative views of mental illness
      were widespread, with as many as 96.5% (s.d.=0.5) believing that people with
      mental illness are dangerous because of their violent behaviour. Most would not
      tolerate even basic social contacts with a mentally ill person: 82.7% (s.e.=1.3)
      would be afraid to have a conversation with a mentally ill person and only 16.9%
      (s.e.=0.9) would consider marrying one. Socio-demographic predictors of both poor
      knowledge and intolerant attitude were generally very few. CONCLUSIONS: There is
      widespread stigmatisation of mental illness in the Nigerian community. Negative
      attitudes to mental illness may be fuelled by notions of causation that suggest
      that affected people are in some way responsible for their illness, and by fear.

PMID- 15863751
TI  - Migration, family dysfunction and psychotic symptoms in children and adolescents.
AB  - A cross-sectional study of 3426 referred children and adolescents showed that the
      presence of both migration history and family dysfunction was associated with a
      fourfold (95% CI 2-9) higher risk of psychotic symptoms compared with the absence
      of these factors. The relative risk was 2 (95% CI 1-4) for migration history
      only. Interaction between migration history and family dysfunction accounted for
      58% (95% CI 5-91%) of those with psychotic symptoms. These results suggest a
      relationship between family dysfunction and migration in the development of
      psychosis.

PMID- 15863752
TI  - Transcranial direct current stimulation.

PMID- 15863753
TI  - Combating editorial racism.

PMID- 15863754
TI  - NICE recommendations for valproate treatment are unhelpful.

PMID- 15863755
TI  - Reading habits of British psychiatrists.

PMID- 15863758
TI  - A post-take ward round.

PMID- 15863759
TI  - Reflections from the GP surgery at the turn of the year.

PMID- 15863760
TI  - More nearly certain.

PMID- 15863762
TI  - Skin and kin.

PMID- 15863761
TI  - Molecular medicine: promises, promises?

PMID- 15863763
TI  - Green medicine.

PMID- 15863764
TI  - Genes and the eye.

PMID- 15863765
TI  - Medical education for the future.

PMID- 15863766
TI  - Talking cure and curing talk.

PMID- 15863767
TI  - Prelude and sarabande.

PMID- 15863768
TI  - The doctor as human being.

PMID- 15863769
TI  - Dean and surgeon.

PMID- 15863770
TI  - Doctor's diary card.

PMID- 15863771
TI  - RENEW 2055: 60 years old and counting.

PMID- 15863773
TI  - For aneurin bevan.

PMID- 15863772
TI  - Standards in the NHS.

PMID- 15863774
TI  - Child abuse and paediatrics.

PMID- 15863775
TI  - Information and communications technology in mental health care.

PMID- 15863776
TI  - What sort of international cooperation in health 2055?

PMID- 15863777
TI  - How I became the proprietor of a house of ill-repute.

PMID- 15863778
TI  - Love sickness and the healing of Rumi.

PMID- 15863779
TI  - A farewell to the flesh?

PMID- 15863780
TI  - Disparate lymphoid chemokine expression in mice and men: no evidence of CCL21
      synthesis by human high endothelial venules.
AB  - T-cell homing to secondary lymphoid tissues generally depends on chemokine
      induced firm adhesion in high endothelial venules (HEVs) and is primarily
      mediated through the CC chemokine receptor 7 (CCR7) on lymphocytes. The CCR7
      ligand designated CCL21 is considered the most important trigger because it
      appears constitutively expressed by murine HEVs. Surprisingly, when we analyzed
      human tissues, no CCL21 mRNA could be detected in HEVs. In fact, CCL21 mRNA was
      only expressed in extravascular T-zone cells and lymphatics, whereas
      immunostaining revealed CCL21 protein within HEVs. This suggests that T-cell
      recruitment to human lymphoid tissues depends on the transcytosis of lymphoid
      chemokines through HEV cells because there is at present no evidence of
      alternative chemokine production in these cells that could explain the attraction
      of naive T lymphocytes.

PMID- 15863781
TI  - Personality disorders come of age.

PMID- 15863782
TI  - The case for practical clinical trials in psychiatry.
AB  - OBJECTIVE: Clinical trials in psychiatry frequently fail to maximize clinical
      utility for practicing clinicians, or, stated differently, available evidence is
      not perceived by clinicians (and other decision makers) as sufficiently relevant
      to clinical practice, thereby diluting its impact. To attain maximum clinical
      relevance and acceptability, researchers must conduct clinical trials designed to
      meet the needs of clinicians and others who are making decisions about patients'
      care. The authors present the case for psychiatry's adoption of the practical
      clinical trials model, which is widely used in research in other areas of
      medicine. METHOD: The authors outline the characteristics and scope of practical
      clinical trials, give examples of practical clinical trials, and discuss the
      challenges of using the practical clinical trials model in psychiatry, including
      issues of funding. RESULTS: Practical clinical trials, which are intended to
      provide generalizable answers to important clinical questions without bias, are
      characterized by eight key features: a straightforward clinically relevant
      question, a representative sample of patients and practice settings, sufficient
      power to identify modest clinically relevant effects, randomization to protect
      against bias, clinical uncertainty regarding the outcome of treatment at the
      patient level, assessment and treatment protocols that enact best clinical
      practices, simple and clinically relevant outcomes, and limited subject and
      investigator burden. CONCLUSIONS: To implement the practical clinical trials
      model in psychiatry will require stable funding for network construction and
      maintenance plus methodological innovation in governance and trial selection,
      assessment, treatment, data management, site management, and data analytic
      procedures.

PMID- 15863783
TI  - Somatoform disorders: time for a new approach in DSM-V.
AB  - OBJECTIVE: DSM-III introduced somatoform disorders as a speculative diagnostic
      category for somatic symptoms "not explained by a general medical condition."
      Although retained and enlarged in DSM-IV, somatoform disorders have been the
      subject of continuing criticism by both professionals and patients. The extended
      period of preparation for DSM-V offers an important opportunity to reconsider the
      category of somatoform disorders. METHOD: Exploration of the diverse aims of a
      diagnostic classification indicates that the authors must not only address the
      conceptual and practical problems associated with this category but also
      reconcile it with the parallel medical descriptive classification of functional
      symptoms and syndromes. RESULTS: The existing somatoform disorders categories
      require modification. The authors favor the radical option of the abolition of
      the categories. Diagnoses currently within somatoform disorders could be
      redistributed into other groupings, and the disorders currently defined solely by
      somatic symptoms could be placed on axis III as "functional somatic symptoms and
      syndromes." Greater use could be made of "psychological factors affecting medical
      condition" on axis I. The authors suggest supplementing the diagnosis of
      functional somatic symptoms with a multiaxial formulation. CONCLUSIONS: The
      authors promote a classification of somatic symptoms in DSM-V that is compatible
      with that used in general medicine and offers new opportunities both for research
      into the etiology and treatment of symptoms and for the greater integration of
      psychiatry into general medical practice.

PMID- 15863784
TI  - Hippocampus, V: studying hippocampal behaviors.

PMID- 15863785
TI  - Dilemmas in the psychotherapy of sexually impulsive patients.

PMID- 15863786
TI  - William Blake (1757-1827).

PMID- 15863787
TI  - Borderline personality disorder in clinical practice.
AB  - OBJECTIVE: Most studies of borderline personality disorder have drawn patients
      from among hospital inpatients or outpatients. The aims of this study were to
      examine the nature of borderline personality disorder patients in everyday
      clinical practice and to use data from a sample of borderline personality
      disorder patients seen in the community to refine the borderline construct.
      METHOD: A random national sample of 117 experienced psychiatrists and
      psychologists from the membership registers of the American Psychiatric
      Association and American Psychological Association provided data on a randomly
      selected patient with borderline personality disorder (N=90) or dysthymic
      disorder (N=27) from their practice. The clinicians provided data on axis I
      comorbidity, axis II comorbidity, and adaptive functioning, as well as a
      personality description of the patient using the Shedler-Westen Assessment
      Procedure-200 (SWAP-200) Q-sort, an instrument designed for assessment and
      taxonomic purposes. Analyses compared borderline personality disorder and
      dysthymic disorder groups on variables of interest and aggregated SWAP-200 items
      across all borderline personality disorder patients to create a composite
      portrait of borderline personality disorder as seen in the community. RESULTS:
      The borderline personality disorder sample strongly resembled previously studied
      borderline personality disorder samples with regard to comorbidity and adaptive
      functioning. However, the SWAP-200 painted a portrait of borderline personality
      disorder patients as having more distress and emotion dysregulation, compared to
      the DSM-IV description. CONCLUSIONS: Borderline personality disorder patients in
      research samples are highly similar to those seen in a cross-section of clinical
      practice. However, several studies have now replicated a portrait of borderline
      personality disorder symptoms that places greater weight than the DSM-IV
      description on the intense psychological pain of these patients and suggests
      candidate diagnostic criteria for DSM-V.

PMID- 15863788
TI  - The changing prevalence and severity of obsessive-compulsive disorder criteria
      from DSM-III to DSM-IV.
AB  - OBJECTIVE: Relative to other mental disorders, the prevalence of obsessive
      compulsive disorder (OCD) in the general population is not well established. Some
      epidemiological surveys have determined the prevalence of DSM-III OCD, but this
      is one of the first reports, to the authors' knowledge, of DSM-IV OCD's
      prevalence. METHOD: Data from the Australian National Survey of Mental Health and
      Well-Being, a nationally representative epidemiological survey of mental
      disorders, were analyzed. The prevalence and associated characteristics of DSM-IV
      OCD were identified, and then the data were rescored for DSM-III OCD. Cases
      defined by each system were compared. RESULTS: The 12-month prevalence of DSM-IV
      OCD was 0.6%, considerably less than found in surveys employing DSM-III
      diagnostic criteria. DSM-IV OCD showed significantly higher levels of
      comorbidity, disability, health service use, and treatment received. CONCLUSIONS:
      Changes in the reported prevalence and severity of OCD between DSM-III and DSM-IV
      cases are most likely a function of the differences in diagnostic criteria
      between DSM-III and DSM-IV.

PMID- 15863790
TI  - Countertransference phenomena and personality pathology in clinical practice: an
      empirical investigation.
AB  - OBJECTIVE: This study provides initial data on the reliability and factor
      structure of a measure of countertransference processes in clinical practice and
      examines the relation between these processes and patients' personality
      pathology. METHOD: A national random sample of 181 psychiatrists and clinical
      psychologists in North America each completed a battery of instruments on a
      randomly selected patient in their care, including measures of axis II symptoms
      and the Countertransference Questionnaire, an instrument designed to assess
      clinicians' cognitive, affective, and behavioral responses in interacting with a
      particular patient. RESULTS: Factor analysis of the Countertransference
      Questionnaire yielded eight clinically and conceptually coherent factors that
      were independent of clinicians' theoretical orientation: 1)
      overwhelmed/disorganized, 2) helpless/inadequate, 3) positive, 4)
      special/overinvolved, 5) sexualized, 6) disengaged, 7) parental/protective, and
      8) criticized/mistreated. The eight factors were associated in predictable ways
      with axis II pathology. An aggregated portrait of countertransference responses
      with narcissistic personality disorder patients provided a clinically rich,
      empirically based description that strongly resembled theoretical and clinical
      accounts. CONCLUSIONS: Countertransference phenomena can be measured in
      clinically sophisticated and psychometrically sound ways that tap the complexity
      of clinicians' reactions toward their patients. Countertransference patterns are
      systematically related to patients' personality pathology across therapeutic
      approaches, suggesting that clinicians, regardless of therapeutic orientation,
      can make diagnostic and therapeutic use of their own responses to the patient.

PMID- 15863789
TI  - Two-year prevalence and stability of individual DSM-IV criteria for schizotypal,
      borderline, avoidant, and obsessive-compulsive personality disorders: toward a
      hybrid model of axis II disorders.
AB  - OBJECTIVE: This study tracked the individual criteria of four DSM-IV personality
      disorders-borderline, schizotypal, avoidant, and obsessive-compulsive personality
      disorders-and how they change over 2 years. METHOD: This clinical sample of
      patients with personality disorders was derived from the Collaborative
      Longitudinal Personality Disorders Study and included all participants with
      borderline, schizotypal, avoidant, or obsessive-compulsive personality disorder
      for whom complete 24-month blind follow-up assessments were obtained (N=474). The
      authors identified and rank-ordered criteria for each of the four personality
      disorders by their variation in prevalence and changeability (remission) over
      time. RESULTS: The most prevalent and least changeable criteria over 2 years were
      paranoid ideation and unusual experiences for schizotypal personality disorder,
      affective instability and anger for borderline personality disorder, feeling
      inadequate and feeling socially inept for avoidant personality disorder, and
      rigidity and problems delegating for obsessive-compulsive personality disorder.
      The least prevalent and most changeable criteria were odd behavior and
      constricted affect for schizotypal personality disorder, self-injury and
      behaviors defending against abandonment for borderline personality disorder,
      avoiding jobs that are interpersonal and avoiding potentially embarrassing
      situations for avoidant personality disorder, and miserly behaviors and strict
      moral behaviors for obsessive-compulsive personality disorder. CONCLUSIONS: These
      patterns highlight that within personality disorders the relatively fixed
      criteria are more trait-like and attitudinal, whereas the relatively intermittent
      criteria are more behavioral and reactive. These patterns suggest that
      personality disorders are hybrids of traits and symptomatic behaviors and that
      the interaction of these elements over time helps determine diagnostic stability.
      These patterns may also inform criterion selection for DSM-V.

PMID- 15863791
TI  - Dissociation, childhood interpersonal trauma, and family functioning in patients
      with somatization disorder.
AB  - OBJECTIVE: The goals of this study were to determine 1) the occurrence of various
      dissociative phenomena in patients with somatization disorder, 2) the occurrence
      of six different types of childhood interpersonal trauma in these patients, and
      3) the nature of these patients' early family environment. METHOD: Twenty-two
      patients with somatization disorder and 19 medical comparison subjects completed
      the Structured Clinical Interview for DSM-IV Dissociative Disorders, the
      Childhood Trauma Interview, and the Family Functioning Scale. RESULTS: The
      somatization disorder patients reported significantly higher level of
      dissociative amnesia than the comparison subjects. The two groups reported
      similar levels of depersonalization, derealization, identity confusion, and
      identity alteration. Somatization disorder patients reported significantly
      greater childhood emotional abuse and more severe forms of physical abuse,
      relative to the comparison subjects, with chronic emotional abuse being the best
      predictor of unexplained symptoms. Childhood sexual abuse, separation/loss, and
      witnessing violence were equally common in the two groups. The somatization
      disorder group reported significantly more family conflict and less family
      cohesion. CONCLUSIONS: Only some types of dissociation are more severe in
      patients with somatization disorder, relative to medical comparison subjects.
      Many patients with somatization disorder are raised in an emotionally cold,
      distant, and unsupportive family environment characterized by chronic emotional
      and physical abuse. Sexual abuse is not a necessary prerequisite for the
      disorder.

PMID- 15863792
TI  - Temperament and character profiles and the dopamine D4 receptor gene in ADHD.
AB  - OBJECTIVE: This study was designed to investigate the link among attention
      deficit hyperactivity disorder (ADHD) in adults, novelty-seeking temperament, and
      the 48-base pair (bp) dopamine D4 receptor (DRD4) gene variant. METHOD: This
      study drew from a larger molecular genetic study of ADHD in which the
      ascertainment criterion was having an affected sibling pair with ADHD. Parents
      (N=171) from 96 families provided data. Of the 171 parents, 56 (33%) had a
      lifetime history of ADHD, with 28 (50%) continuing to meet DSM-IV criteria (i.e.,
      "persistent" ADHD). Latent variable modeling was used to test whether the DRD4
      gene variant or Temperament and Character Inventory factors could predict ADHD.
      RESULTS: Using latent variable modeling, the authors were able to confirm the
      first-order factor structure of the Temperament and Character Inventory.
      Furthermore, novelty seeking predicted ADHD lifetime diagnosis (R(2)=26%), while
      the DRD4 gene variant independently predicted ADHD (R(2)=5%) but not novelty
      seeking. CONCLUSIONS: In this unique sample of parents from multiply affected
      ADHD families, novelty seeking and the 48-bp DRD4 variant were associated with a
      lifetime history of ADHD. However, the association between novelty seeking and
      ADHD does not appear to be due to variation in the 48-bp DRD4 variant.

PMID- 15863793
TI  - Brain serotonin transporter distribution in subjects with impulsive aggressivity:
      a positron emission study with [11C]McN 5652.
AB  - OBJECTIVE: The serotonin system is believed to play a role in modulating
      impulsivity and violence. Previous imaging studies have implicated the anterior
      cingulate and orbitofrontal cortex in impulsive aggression. This study evaluated
      regional serotonin transporter distribution in the brain of individuals with
      impulsive aggression by using positron emission tomography (PET) with the
      serotonin transporter PET radiotracer [(11)C]McN 5652. METHOD: Ten individuals
      with impulsive aggression and 10 age- and sex-matched healthy comparison subjects
      underwent [(11)C]McN 5652 PET. All individuals were medication free at the time
      of scanning. Regional total distribution volumes were derived by using a one
      tissue compartment kinetic model with arterial input function. Outcome measures
      of serotonin transporter availability included the binding potential and the
      specific-to-nonspecific partition coefficient (V(3)''). RESULTS: Serotonin
      transporter availability was significantly reduced in the anterior cingulate
      cortex of individuals with impulsive aggression compared with healthy subjects,
      as noted by differences in both binding potential (mean=3.1 ml/g [SD=1.9] versus
      5.0 ml/g [SD=2.0], respectively) and V(3)'' (mean=0.15 [SD=0.09] versus 0.26
      [SD=0.09]). In other regions examined, serotonin transporter density was
      nonsignificantly lower in individuals with impulsive aggression compared with
      healthy subjects. CONCLUSIONS: Pathological impulsive aggressivity might be
      associated with lower serotonergic innervation in the anterior cingulate cortex,
      a region that plays an important role in affective regulation.

PMID- 15863794
TI  - Association of the serotonin transporter gene with smoking behavior.
AB  - OBJECTIVE: In an ongoing molecular genetic study of temperament, participants
      were genotyped to examine the association of smoking with two polymorphisms of
      the serotonin transporter gene (SERT): the promoter region, 5-HTTLPR, and an
      intronic variable-number-of-tandem-repeats region (VNTR). METHOD: Full
      information was available for 330 families, and 244 "ever smokers" were
      identified (54 past smokers, 190 current smokers). The average number of
      cigarettes smoked per day was 13.12, and the mean Fagerstrom Tolerance
      Questionnaire score was 4.79. Associations of genotype, Tridimensional
      Personality Questionnaire scores, and smoking phenotype were tested by using a
      robust family design with a variance-components framework and by case-control
      analysis. RESULTS: There was a significant excess of the 5-HTTLPR long allele
      with the 12-repeat VNTR in current smokers, past smokers, and ever smokers,
      compared to participants who had never smoked. The results from the population
      design were confirmed in the family-based analysis. No association was observed
      between two quantitative measures of smoking and the polymorphisms. A weak
      association was observed between novelty seeking and the VNTR polymorphism and
      between reward and 5-HTTLPR. Smokers, regardless of gender, scored significantly
      higher on novelty seeking and did not differ on harm avoidance or reward.
      CONCLUSIONS: There was a highly significant association between SERT and the
      categorical definition of smoking, irrespective of dependence level, suggesting
      that this gene influences the initiation of smoking. Mediation analysis failed to
      substantiate the hypothesis that novelty seeking partially mediates the effect of
      SERT on smoking. SERT appears to independently contribute to novelty seeking and
      smoking.

PMID- 15863795
TI  - Thalamic and prefrontal FDG uptake in never medicated patients with
      schizophrenia.
AB  - OBJECTIVE: Because neuroleptic treatment may cause long-lasting changes in brain
      structure and function, a group of patients with schizophrenia who had never been
      medicated was recruited to examine regional glucose metabolic rates in the
      frontal-striato-thalamic circuit. METHOD: Twelve never medicated patients with
      schizophrenia (seven men, five women; mean age=29 years) and 13 normal volunteers
      (eight men and five women; mean age=28.5 years) underwent (18)F
      fluorodeoxyglucose (FDG) positron emission tomography, and coregistered
      anatomical magnetic resonance imaging scans were also obtained. During FDG
      uptake, subjects performed a spatial attention task previously shown to activate
      the pulvinar region of the thalamus. RESULTS: Diminished regional glucose
      metabolism was found in the medial dorsal nucleus, posterior thalamus, and
      prefrontal cortex of patients with schizophrenia relative to normal volunteers,
      extending earlier results from studies of medicated and previously medicated
      patients. CONCLUSIONS: The finding of lower relative metabolic rates in the
      frontothalamic circuits of patients with schizophrenia is consistent with
      extended circuit deficits involving interactions of frontal executive areas with
      thalamic sensory and association processes.

PMID- 15863796
TI  - Evidence for onset of antipsychotic effects within the first 24 hours of
      treatment.
AB  - OBJECTIVE: It is widely held that there is a delayed onset of antipsychotic
      action and that any early effects represent nonspecific behavioral effects.
      Recent research has shown that antipsychotic action begins within the first week.
      The authors tested the hypothesis that psychosis improves within the first 24
      hours of antipsychotic treatment. METHOD: In this multicenter, double-blind,
      placebo-controlled study, 311 patients with a diagnosis of schizophrenia spectrum
      disorder and an acute exacerbation were randomly assigned to receive 10 mg i.m.
      of olanzapine, 7.5 mg i.m. of haloperidol, or intramuscular placebo. Subjects
      were rated with structured rating scales (Positive and Negative Syndrome Scale
      and Clinical Global Impression) at baseline, 2 hours, and 24 hours. RESULTS: The
      olanzapine and haloperidol groups showed greater resolution of overall symptoms
      than the placebo group; for the olanzapine group, this effect was evident at 2
      hours. A factor analysis showed that an independent change in psychosis (which
      included conceptual disorganization, hallucinatory behavior, unusual thought
      content) was evident within the first 24 hours for both drugs. This improvement
      in core psychosis was not mediated unidirectionally by changes in nonspecific
      behavioral effects or other psychopathology. CONCLUSIONS: These data suggest that
      the onset of antipsychotic action is early and that the magnitude of this action
      grows with time. This clinical reality calls into question some prevailing
      hypotheses regarding the mechanism of action of antipsychotics and suggests that
      antipsychotic action may be more proximally related to the blockade of dopamine
      transmission than was originally thought.

PMID- 15863798
TI  - A double-blind, placebo-controlled trial of sibutramine for olanzapine-associated
      weight gain.
AB  - OBJECTIVE: Weight gain is commonly observed with olanzapine treatment and can
      increase the risk for obesity, cardiovascular disease, hypertension, and diabetes
      mellitus. This study examined the effectiveness of sibutramine, an approved
      weight loss agent, in overweight and obese subjects taking olanzapine for
      schizophrenia or schizoaffective disorder. METHOD: Each subject had a DSM-IV
      diagnosis of schizophrenia or schizoaffective disorder, had been taking a stable
      dose of olanzapine for at least 4 months, and had a body mass index of >/=30
      kg/m(2) or >/=27 kg/m(2) plus at least one cardiovascular risk factor. In a 12
      week double-blind, randomized, placebo-controlled study, 37 subjects received
      placebo or sibutramine (up to 15 mg/day). For the first 8 weeks all subjects
      participated in weekly group sessions focused on nutrition and behavioral
      modification. RESULTS: The sibutramine and placebo groups had no significant
      baseline differences on age, gender, education, ethnicity, diagnosis, weight,
      body mass index, and blood pressure. At week 12 the sibutramine group had
      significantly greater losses than the placebo group in weight (mean=8.3 lb,
      SD=2.4, versus mean=1.8 lb, SD=1.6), waist circumference, body mass index, and
      hemoglobin A(1c). There were no significant differences on most side effects,
      although the sibutramine group exhibited a mean increase in systolic blood
      pressure of 2.1 mm Hg (SD=8.5), and anticholinergic side effects and sleep
      disturbances were at least twice as common in the sibutramine group. CONCLUSIONS:
      Sibutramine was an effective and well-tolerated adjunct to behavior modification
      for weight loss in patients with schizophrenia and schizoaffective disorder being
      treated with olanzapine.

PMID- 15863797
TI  - Risperidone and haloperidol in first-episode psychosis: a long-term randomized
      trial.
AB  - OBJECTIVE: The first episode of psychotic illness is a key intervention point.
      The initial experience with medication can affect willingness to accept
      treatment. Further, relapse prevention is a treatment cornerstone during the
      first years of illness because active psychotic illness may affect lifetime
      outcomes. Thus, initial treatment of active symptoms and subsequent relapse
      prevention are central goals of pharmacotherapy. This study compared long-term
      effectiveness of risperidone versus haloperidol in first-episode psychosis
      patients. METHOD: First-episode psychosis patients (N=555, mean age=25.4 years)
      participated in a double-blind, randomized, controlled flexible-dose trial that
      compared risperidone (mean modal dose=3.3 mg) and haloperidol (mean modal
      dose=2.9 mg). The median treatment length was 206 days (maximum=1,514). RESULTS:
      Positive and Negative Syndrome Scale scores and Clinical Global Impression
      ratings improved significantly relative to baseline, with no significant
      differences between groups. Three-quarters of the patients achieved initial
      clinical improvement, defined as >20% reduction in total Positive and Negative
      Syndrome Scale score. However, among those who achieved clinical improvement, 42%
      of the risperidone group experienced a relapse compared with 55% of the
      haloperidol group. The median time to relapse was 466 days for risperidone
      treated subjects and 205 days for those given haloperidol. These differences were
      statistically significant based on Kaplan-Meier survival analysis. Adverse
      effects distinguished the treatments: there were significantly more
      extrapyramidal signs and symptoms and adjunctive medication use in the
      haloperidol group and greater prolactin elevation in the risperidone group. There
      was less weight gain with haloperidol initially but no significant differences
      between groups at endpoint. CONCLUSIONS: Relatively low doses of antipsychotic
      drugs lead to significant symptom amelioration in the majority of first-episode
      psychosis patients. In the long term, risperidone prevents relapse in more
      patients and for a longer time and also induces less abnormal movements than
      haloperidol.

PMID- 15863799
TI  - Does memory of a traumatic event increase the risk for posttraumatic stress
      disorder in patients with traumatic brain injury? A prospective study.
AB  - OBJECTIVE: The present study examined prospectively the relationship between
      memory of the traumatic event and subsequent development of posttraumatic stress
      disorder (PTSD). More specifically, the aims of this study were to 1) investigate
      the possibility that lack of memory of the traumatic event might be a protective
      factor; 2) assess whether memory of the traumatic event equally affects the three
      symptom clusters of PTSD: reexperiencing, avoidance, and hyperarousal; and 3)
      explore the predictive value of memory of the traumatic event for the development
      of subsequent PTSD in the immediate aftermath of the event. METHOD: One hundred
      twenty subjects with mild traumatic brain injury who were hospitalized for
      observation were assessed immediately after the trauma and followed up 1 week, 3
      months, and 6 months later. All participants underwent psychiatric evaluation and
      self-assessment of their memory of the traumatic event. RESULTS: Overall, 17
      (14%) of the participants met full criteria for PTSD at 6 months. Subjects with
      memory of the traumatic event were significantly more likely to develop PTSD than
      those without memory of the traumatic event; the difference between the groups
      resulted primarily from the reexperiencing cluster. Logistic regression analysis
      revealed that memory of the traumatic event within the first 24 hours is a strong
      predictor of PTSD 6 months after the event. CONCLUSIONS: Our study indicated that
      memory of a traumatic event is a strong predictor and a potential risk factor for
      subsequent development of PTSD. Future studies are needed to show whether these
      findings can be generalized to other traumatic conditions.

PMID- 15863800
TI  - The impact of comorbid posttraumatic stress disorder on short-term clinical
      outcome in hospitalized patients with depression.
AB  - OBJECTIVE: Posttraumatic stress disorder (PTSD) is often comorbid with other
      psychiatric disorders but often goes unrecognized. The effects of PTSD
      comorbidity are unclear, especially in patients with severe mental illness. The
      authors assessed short-term clinical outcome in severely depressed psychiatric
      inpatients with and without comorbid PTSD. METHOD: From patients hospitalized
      between 1995 and 2000, all patients with depression and comorbid PTSD (N=587)
      were selected and matched with depressed patients without PTSD (N=587). Clinical
      outcome was assessed with a semistructured, physician-administered battery.
      Differences between the two groups were examined, with overall burden of
      psychiatric illness entered as a covariate in the analyses. RESULTS: Relative to
      depressed patients without PTSD, depressed patients with PTSD had, at discharge,
      greater psychiatric symptom severity and higher levels of depression and
      hostility. Depressed patients with comorbid PTSD also had a significantly higher
      rate of being discharged against medical advice (odds ratio=6.10, 95% CI 2.96
      12.57). CONCLUSIONS: PTSD comorbidity correlates with poorer short-term clinical
      outcome and greater likelihood of discharge against medical advice in severely
      depressed psychiatric inpatients. Better recognition of PTSD comorbidity may
      improve overall care of these patients.

PMID- 15863802
TI  - Functional brain imaging alterations in acne patients treated with isotretinoin.
AB  - OBJECTIVE: Although there have been case reports suggesting a relationship
      between treatment with the acne medication isotretinoin and the development of
      depression and suicide, this topic remains controversial. In order for
      isotretinoin to cause depression, it must have an effect on the brain; however,
      the effects of isotretinoin on brain functioning in acne patients have not been
      established. The purpose of this study was to assess the effects of isotretinoin
      on brain functioning in acne patients. METHOD: Brain functioning in adults was
      measured with [(18)F]fluorodeoxyglucose positron emission tomography before and
      after 4 months of treatment with isotretinoin (N=13) or an antibiotic (N=15).
      RESULTS: Isotretinoin but not antibiotic treatment was associated with decreased
      brain metabolism in the orbitofrontal cortex (-21% change versus 2% change for
      antibiotic), a brain area known to mediate symptoms of depression. There were no
      differences in the severity of depressive symptoms between the isotretinoin and
      antibiotic treatment groups before or after treatment. CONCLUSIONS: This study
      suggests that isotretinoin treatment is associated with changes in brain
      functioning.

PMID- 15863803
TI  - Higher levels of basal serial CSF cortisol in combat veterans with posttraumatic
      stress disorder.
AB  - OBJECTIVE: Results of basal peripheral cortisol measures in posttraumatic stress
      disorder (PTSD) have been variable. The authors' goal was to measure CSF cortisol
      concentrations, which more accurately reflect brain glucocorticoid exposure, in
      subjects with or without PTSD. METHOD: CSF was withdrawn from a subarachnoid
      catheter and plasma from a venous catheter, both indwelling, over a 6-hour
      interval to determine hourly plasma ACTH and cortisol concentrations and hourly
      CSF cortisol levels in eight well-characterized combat veterans with PTSD and
      eight matched healthy volunteers. RESULTS: Mean CSF cortisol concentrations were
      significantly higher in the subjects with PTSD (3.18 ng/ml, SD=0.33) than in the
      normal volunteers (2.33 ng/ml, SD=0.50), largely due to higher CSF cortisol
      concentration nadirs. No group differences were observed in either plasma ACTH or
      peripheral (plasma or urinary free) cortisol. CSF corticotropin-releasing hormone
      and CSF cortisol concentrations were positively and significantly correlated.
      CONCLUSIONS: Despite normal peripheral cortisol indexes in the veterans with
      PTSD, their CNS exposure to cortisol was greater than that of normal comparison
      subjects.

PMID- 15863801
TI  - Relief of expressed suicidal intent by ECT: a consortium for research in ECT
      study.
AB  - OBJECTIVE: This study assessed the incidence, severity, and course of expressed
      suicidal intent in depressed patients who were treated with ECT. The data are
      from the first phase of an ongoing, collaborative multicenter study, the overall
      aim of which was to compare continuation ECT with pharmacotherapy in the
      prevention of relapse after a successful course of ECT. METHOD: Suicidal intent,
      as expressed by patients during an interview, was scored at baseline and before
      each ECT session with item 3 on the 24-item Hamilton Depression Rating Scale in
      444 patients with unipolar depression. RESULTS: One hundred thirty-one patients
      (29.5%) reported suicidal thoughts and acts (score of 3 or 4) at baseline. Scores
      decreased to 0 after 1 week (three ECT sessions) in 38.2% of the patients, after
      2 weeks (six ECT sessions) in 61.1%, and in 80.9% at the end of the course of
      treatment. CONCLUSIONS: Expressed suicidal intent in depressed patients was
      rapidly relieved with ECT. Evidence-based treatment algorithms for major
      depressive mood disorders should include dichotomization according to suicide
      risk, as assessed by interview. For patients at risk, ECT should be considered
      earlier than at its conventional "last resort" position.

PMID- 15863804
TI  - Childhood trauma and personality disorder: positive correlation with adult CSF
      corticotropin-releasing factor concentrations.
AB  - OBJECTIVE: To test the hypothesis that early life trauma results in adult stress
      hormone alterations in individuals with personality disorders, the authors
      examined the relationship between history of childhood adversity and lumbar CSF
      corticotropin-releasing factor (CRF). METHOD: Participants were 20 otherwise
      healthy men who met DSM-IV criteria for personality disorders. CSF CRF was
      obtained by lumbar puncture, and childhood adversity was measured by the
      Childhood Trauma Questionnaire. Correlations were obtained between CSF CRF and
      the total score on the Childhood Trauma Questionnaire as well as scores on its
      four subscales. RESULTS: CSF CRF concentrations were positively correlated with
      the total score on the Childhood Trauma Questionnaire. Analysis of the subscales
      revealed that CSF CRF was correlated with emotional neglect. Correlations between
      CSF CRF level and physical and emotional abuse and with physical neglect were not
      statistically significant. CONCLUSIONS: Consistent with the hypothesis that the
      severity of early life stress is correlated with stress hormone abnormalities in
      adulthood, Childhood Trauma Questionnaire total scores and emotional neglect
      scores were significantly correlated with CSF CRF levels in individuals with
      personality disorders.

PMID- 15863805
TI  - Circadian rhythm of salivary cortisol in Holocaust survivors with and without
      PTSD.
AB  - OBJECTIVE: The authors' goal was to determine whether cortisol circadian rhythm
      alterations observed in younger subjects with posttraumatic stress disorder
      (PTSD) are also present in geriatric trauma survivors with PTSD. METHOD: Salivary
      cortisol levels were measured at six intervals from awakening until bedtime in 23
      Holocaust survivors with PTSD, 19 Holocaust survivors without PTSD, and 25
      subjects who had not been exposed to the Holocaust. Thirty-three of the subjects
      were men, and 34 were women. RESULTS: Cortisol levels were significantly lower at
      awakening, at 8:00 a.m., and at 8:00 p.m. in Holocaust survivors with PTSD than
      in nonexposed subjects, resulting in a flatter circadian rhythm, similar to what
      has been observed in aging but different from what has been reported in younger
      subjects with PTSD. CONCLUSIONS: These data provide evidence of differential
      neuroendocrine alterations in geriatric PTSD.

PMID- 15863806
TI  - Posttraumatic stress disorder and memory problems after female genital
      mutilation.
AB  - OBJECTIVE: This pilot study investigated the mental health status of women after
      genital mutilation. Although experts have assumed that circumcised women are more
      prone to developing psychiatric illnesses than the general population, there has
      been little research to confirm this claim. It was predicted that female genital
      mutilation is associated with a high rate of posttraumatic stress disorder
      (PTSD). METHOD: The psychological impact of female genital mutilation was
      assessed in 23 circumcised Senegalese women in Dakar. Twenty-four uncircumcised
      Senegalese women served as comparison subjects. A neuropsychiatric interview and
      further questionnaires were used to assess traumatization and psychiatric
      illnesses. RESULTS: The circumcised women showed a significantly higher
      prevalence of PTSD (30.4%) and other psychiatric syndromes (47.9%) than the
      uncircumcised women. PTSD was accompanied by memory problems. CONCLUSIONS: Within
      the circumcised group, a mental health problem exists that may furnish the first
      evidence of the severe psychological consequences of female genital mutilation.

PMID- 15863807
TI  - Alcohol and aldehyde dehydrogenase polymorphisms in men with type I and Type II
      alcoholism.
AB  - OBJECTIVE: The authors examined the genetic polymorphisms of alcohol
      dehydrogenase 2 and 3 (ADH2 and ADH3) and aldehyde dehydrogenase (ALDH2) in
      patients diagnosed as having Cloninger's type I or type II alcoholism. METHOD:
      Seventy-two alcoholic men and 38 nonalcoholic, healthy men were tested for the
      distribution of genotypes and alleles of ADH2, ADH3, and ALDH2. Forty-eight of
      the alcoholic men had type I alcoholism, and 24 had type II alcoholism. RESULTS:
      The frequencies of ADH2*1 and ADH3*2 alleles were significantly higher in men
      with type II alcoholism than in men with type I alcoholism and healthy men. The
      frequency of the ALDH2*1 allele was significantly higher in men with alcohol
      dependence than in healthy men. CONCLUSIONS: The genetic characteristics of
      alcohol dehydrogenases in men with type I alcoholism were similar to those of
      healthy men, and the genetic characteristics of aldehyde dehydrogenase in men
      with type I alcoholism were similar to those of men with type II alcoholism.
      These findings suggest that the genetic characteristics of alcohol metabolism in
      type I alcoholism fall between nonalcoholism and type II alcoholism.

PMID- 15863808
TI  - Association of genetic variants in alcohol dehydrogenase 4 with alcohol
      dependence in Brazilian patients.
AB  - OBJECTIVE: The authors evaluated the association of three functional promoter
      polymorphisms of the ADH4 gene with alcohol dependence. METHOD: DNA from 92
      alcohol-dependent patients and 92 healthy comparison subjects was genotyped for
      all three polymorphisms. RESULTS: Variants at the -75 base-pair (bp) (C allele)
      and -159 bp (A allele) positions were associated with alcohol dependence.
      Individuals with haplotypes carrying both risk alleles showed an odds ratio of
      2.9. CONCLUSIONS: These preliminary results suggest that ADH4 may play a role in
      the etiology of alcohol dependence. The association requires further study and
      replication but is functionally plausible and has a large effect size.

PMID- 15863809
TI  - Substance abuse in first-episode bipolar I disorder: indications for early
      intervention.
AB  - OBJECTIVE: This study clarified the early characteristics of substance use
      disorders in patients with first-episode bipolar I disorder. METHOD: The authors
      evaluated substance use disorders, associated factors, and clinical course,
      prospectively, in the first 2 years of DSM-IV bipolar I disorder with
      standardized methods. RESULTS: Baseline substance use disorder was found in 33%
      (37 of 112) of the patients at baseline and in 39% at 24 months. Anxiety
      disorders were more frequent in the patients with than without substance use
      disorder (30% and 13%, respectively). Associations of alcohol dependence with
      depressive symptoms and cannabis dependence with manic symptoms were suggested.
      Patients using two or more substances had worse outcomes. CONCLUSIONS: Since
      substance use disorders were frequent from the beginning of bipolar I disorder
      and were associated with anxiety disorders and poor outcome, early interventions
      for substance use disorder and anxiety might improve later outcome.

PMID- 15863810
TI  - Predominant role of the 9-hydroxy metabolite of risperidone in elevating blood
      prolactin levels.
AB  - OBJECTIVE: The atypical antipsychotic risperidone significantly raises plasma
      prolactin levels in patients, but clozapine, olanzapine, and quetiapine do not.
      The differences in neuroendocrine response may be connected with the metabolism
      of the medications. The authors examined the contributory role of risperidone's
      active metabolite 9-hydroxy-risperidone by measuring plasma concentrations of
      risperidone, 9-hydroxy-risperidone, and prolactin. METHOD: Blood samples taken
      from 25 patients with psychotic disorders following 6 weeks of treatment with
      risperidone (mean dose=3 mg/day) were examined. Mean plasma concentrations of
      risperidone, 9-hydroxy-risperidone, and prolactin were 4.6, 19.4, and 49.3 ng/ml,
      respectively. RESULTS: The oral dose of risperidone correlated significantly with
      plasma concentrations of risperidone, 9-hydroxy-risperidone, active moiety, and
      prolactin. The plasma concentration of 9-hydroxy-risperidone, but not of
      risperidone, correlated significantly with increases in plasma prolactin.
      CONCLUSIONS: These data suggest that the 9-hydroxy metabolite plays a predominant
      role in risperidone's effect on prolactin release.

PMID- 15863811
TI  - The effects of clozapine and risperidone on spatial working memory in
      schizophrenia.
AB  - OBJECTIVE: The purpose of this investigation was to evaluate the effects of
      clozapine and risperidone on spatial working memory in patients with
      schizophrenia. METHOD: Spatial working memory performance was evaluated at
      baseline and after 17 and 29 weeks in 97 patients with schizophrenia
      participating in a multisite trial. RESULTS: Compared with baseline performance
      while receiving conventional antipsychotic medication, risperidone improved, and
      clozapine worsened, spatial working memory performance. CONCLUSIONS: The
      differential effects of these medications on spatial working memory may be due to
      the anticholinergic effects of clozapine and prefrontal dopamine-enhancing
      effects of risperidone.

PMID- 15863813
TI  - Low IQ and gasoline huffing: the perpetuation cycle.

PMID- 15863812
TI  - Familial aggregation of suicidal behavior: a family study of male suicide
      completers from the general population.
AB  - OBJECTIVE: This study compared suicidality in families of adult male suicide
      completers and community comparison subjects. METHOD: Two hundred forty-seven
      relatives of 25 male suicide completers and 171 relatives of 25 matched
      comparison subjects were assessed for recurrent risk of suicidal and related
      behaviors. Analyses were performed on a subgroup of relatives of suicide
      completers with cluster B personality disorders. RESULTS: Relatives of suicide
      completers were over 10 times more likely than relatives of comparison subjects
      to attempt or complete suicide after the authors controlled for psychopathology.
      Relatives of suicide completers were not more likely to exhibit suicidal ideation
      but had more severe suicidal ideation than relatives of comparison subjects.
      These findings were stronger for the suicide completers diagnosed with cluster B
      personality disorders. CONCLUSIONS: Suicide has a familial component independent
      of psychopathology that may be mediated by a combination of factors, including
      more severe suicidal ideation and aggressive behavior.

PMID- 15863814
TI  - Quetiapine discontinuation syndrome.

PMID- 15863815
TI  - Bipolar disorder and Niemann-Pick disease type C.

PMID- 15863816
TI  - Anticonvulsant hypersensitivity syndrome from addition of lamotrigine to
      divalproex.

PMID- 15863817
TI  - Olanzapine augmentation of fluoxetine in body dysmorphic disorder.

PMID- 15863818
TI  - Suicide and latitude in Argentina: Durkheim upside-down.

PMID- 15863819
TI  - Pilocarpine treatment of xerostomia induced by psychoactive medications.

PMID- 15863820
TI  - Cancer risk in parents of patients with schizophrenia.

PMID- 15863821
TI  - Sertraline for recurrent major depression.

PMID- 15863822
TI  - Irritability and depression.

PMID- 15863823
TI  - Psychotropic medication and stroke outcome.

PMID- 15863824
TI  - Psychiatry and general practitioners.

PMID- 15863825
TI  - Psychotropic medication and stroke outcome.

PMID- 15863826
TI  - Tobacco use and cataracts in patients with schizophrenia.

PMID- 15863827
TI  - Tobacco use and cataracts in patients with schizophrenia.

PMID- 15863828
TI  - Alexithymia, personality, and psychopathology.

PMID- 15863829
TI  - Refining the personality disorder diagnosis.

PMID- 15863830
TI  - Comment on hoarding.

PMID- 15863831
TI  - Dramatic broadening of the substrate profile of the Aeromonas hydrophila CphA
      metallo-beta-lactamase by site-directed mutagenesis.
AB  - Among class B beta-lactamases, the subclass B2 CphA enzyme is characterized by a
      unique specificity profile. CphA efficiently hydrolyzes only carbapenems. In this
      work, we generated site-directed mutants that possess a strongly broadened
      activity spectrum when compared with the WT CphA. Strikingly, the N116H/N220G
      double mutant exhibits a substrate profile close to that observed for the broad
      spectrum subclass B1 enzymes. The double mutant is significantly activated by the
      binding of a second zinc ion under conditions where the WT enzyme is non
      competitively inhibited by the same ion.

PMID- 15863832
TI  - Fatty acid transfer from intestinal fatty acid binding protein to membranes:
      electrostatic and hydrophobic interactions.
AB  - Intestinal fatty acid binding protein (IFABP) is thought to participate in the
      intracellular transport of fatty acids (FAs). Fatty acid transfer from IFABP to
      phospholipid membranes is proposed to occur during protein-membrane collisional
      interactions. In this study, we analyzed the participation of electrostatic and
      hydrophobic interactions in the collisional mechanism of FA transfer from IFABP
      to membranes. Using a fluorescence resonance energy transfer assay, we examined
      the rate and mechanism of transfer of anthroyloxy-fatty acid analogs a) from
      IFABP to phospholipid membranes of different composition; b) from chemically
      modified IFABPs, in which the acetylation of surface lysine residues eliminated
      positive surface charges; and c) as a function of ionic strength. The results
      show clearly that negative charges on the membrane surface and positive charges
      on the protein surface are important for establishing the "collisional complex",
      during which fatty acid transfer occurs. In addition, changes in the
      hydrophobicity of the protein surface, as well as the hydrophobic volume of the
      acceptor vesicles, also influenced the rate of fatty acid transfer. Thus, ionic
      interactions between IFABP and membranes appear to play a primary role in the
      process of fatty acid transfer to membranes, and hydrophobic interactions can
      also modulate the rates of ligand transfer.

PMID- 15863833
TI  - The apoE isoform binding properties of the VLDL receptor reveal marked
      differences from LRP and the LDL receptor.
AB  - Apolipoprotein E (apoE) associates with lipoproteins and mediates their
      interaction with members of the LDL receptor family. ApoE exists as three common
      isoforms that have important distinct functional and biological properties. Two
      apoE isoforms, apoE3 and apoE4, are recognized by the LDL receptor, whereas apoE2
      binds poorly to this receptor and is associated with type III hyperlipidemia. In
      addition, the apoE4 isoform is associated with the common late-onset familial and
      sporadic forms of Alzheimer's disease. Although the interaction of apoE with the
      LDL receptor is well characterized, the specificity of other members of this
      receptor family for apoE is poorly understood. In the current investigation, we
      have characterized the binding of apoE to the VLDL receptor and the LDL receptor
      related protein (LRP). Our results indicate that like the LDL receptor, LRP
      prefers lipid-bound forms of apoE, but in contrast to the LDL receptor, both LRP
      and the VLDL receptor recognize all apoE isoforms. Interestingly, the VLDL
      receptor does not require the association of apoE with lipid for optimal
      recognition and avidly binds lipid-free apoE. It is likely that this receptor
      dependent specificity for various apoE isoforms and for lipid-free versus lipid
      bound forms of apoE is physiologically significant and is connected to distinct
      functions for these receptors.

PMID- 15863834
TI  - Domain-specific lipid distribution in macrophage plasma membranes.
AB  - Lipid rafts, defined as cholesterol- and sphingolipid-rich domains, provide
      specialized lipid environments understood to regulate the organization and
      function of many plasma membrane proteins. Growing evidence of their existence,
      protein cargo, and regulation is based largely on the study of isolated lipid
      rafts; however, the consistency and validity of common isolation methods is
      controversial. Here, we provide a detailed and direct comparison of the lipid and
      protein composition of plasma membrane "rafts" prepared from human macrophages by
      different methods, including several detergent-based isolations and a detergent
      free method. We find that detergent-based and detergent-free methods can generate
      raft fractions with similar lipid contents and a biophysical structure close to
      that previously found on living cells, even in cells not expressing caveolin-1,
      such as primary human macrophages. However, important differences between
      isolation methods are demonstrated. Triton X-100-resistant rafts are less
      sensitive to cholesterol or sphingomyelin depletion than those prepared by
      detergent-free methods. Moreover, we show that detergent-based methods can
      scramble membrane lipids during the isolation process, reorganizing lipids
      previously in sonication-derived nonraft domains to generate new detergent
      resistant rafts. The role of rafts in regulating the biological activities of
      macrophage plasma membrane proteins may require careful reevaluation using
      multiple isolation procedures, analyses of lipids, and microscopic techniques.

PMID- 15863835
TI  - Ceramide displaces cholesterol from lipid rafts and decreases the association of
      the cholesterol binding protein caveolin-1.
AB  - Addition of exogenous ceramide causes a significant displacement of cholesterol
      in lipid raft model membranes. However, whether ceramide-induced cholesterol
      displacement is sufficient to alter the protein composition of caveolin-enriched
      lipid raft membranes is unknown. Therefore, we examined whether increasing
      endogenous ceramide levels with bacterial sphingomyelinase (bSMase) depleted
      cholesterol and changed the protein composition of caveolin-enriched membranes
      (CEMs) isolated from immortalized Schwann cells. bSMase increased ceramide levels
      severalfold and decreased the cholesterol content of detergent-insoluble CEMs by
      25-50% within 2 h. To examine the effect of ceramide on the protein composition
      of the CEMs, we performed a quantitative proteomic analysis using stable isotope
      labeling of cells in culture and matrix-assisted laser desorption ionization time
      of-flight mass spectrometry. Although ceramide rapidly depleted lipid raft
      cholesterol, the levels of the cholesterol binding protein caveolin-1 (Cav-1)
      decreased by 25% only after 8 h. Importantly, replenishing the cells with
      cholesterol rapidly reversed the loss of Cav-1 from the CEMs. Ceramide-induced
      cholesterol depletion increased the association of 5'-nucleotidase and ATP
      synthase beta-subunit with the CEMs but had a minimal effect on changing the
      abundance of other lipid raft proteins, such as flotillin-1 and G-proteins. These
      results suggest that the ceramide-induced loss of cholesterol from CEMs may
      contribute to altering the lipid raft proteome.

PMID- 15863836
TI  - Peptide inhibitor of pancreatic lipase selected by phage display using different
      elution strategies.
AB  - Interference with fat hydrolysis results in the reduced use of ingested lipids.
      Inhibition of pancreatic lipase reduces the efficiency of fat absorption in the
      small intestine and thereby initiates modest long-term reduction in body weight.
      In an attempt to select peptides with affinity for the surface of pancreatic
      lipase and potential inhibitory activity, a random, cyclic heptapeptide phage
      displayed library was used. Five independent selections, differing in elution
      step, were performed. In three selection protocols, a sequential elution strategy
      was applied in anticipation of improving the selection of high-affinity clones.
      Four heptapeptides with the highest affinity, seemingly for pancreatic lipase,
      were selected, synthesized, and characterized for their capacity to inhibit
      enzyme function. Although no clear consensus among the sequenced peptides was
      found, one of the selected peptides inhibited pancreatic lipase with an apparent
      inhibition constant of 16 muM.

PMID- 15863837
TI  - Differential regulation and properties of angiopoietin-like proteins 3 and 4.
AB  - Angiopoietin-like protein 3 and 4 (Angptl3 and Angptl4) are two members of the
      angiopoietin-like family of proteins. These two closely related proteins have
      been reported to similarly affect lipid metabolism through their capacity to
      inhibit lipoprotein lipase. We undertook a series of studies to compare the
      structure, function, and regulation of Angptl3 and Angptl4. Previously, we
      reported that Angptl4 exists as variable-sized oligomers that contain
      intermolecular disulfide bonds. We now have evidence that although there are no
      intermolecular disulfide bonds evident in Angptl3, higher molecular weight forms
      do exist. In addition, Angptl4 exhibits a widespread distribution of tissue
      expression, while Angptl3 is exclusively expressed in the liver. Treatments with
      various ligands of nuclear receptors reveal that Angptl3 is a target gene of
      liver X receptor, while Angptl4 expression is activated by ligands of all
      peroxisome proliferator-activated receptors. Expression of Angptl4 in adipose
      tissue and liver is induced by fasting, while Angptl3 expression is not
      appreciably affected by nutritional status. We suggest that the differential
      regulation of Angptl3 and Angptl4 by sites of expression, nutritional status, and
      ligands of nuclear receptors may confer unique roles of each in lipoprotein
      metabolism.

PMID- 15863838
TI  - ApoC-III deficiency prevents hyperlipidemia induced by apoE overexpression.
AB  - Adenovirus-mediated overexpression of human apolipoprotein E (apoE) induces
      hyperlipidemia by stimulating the VLDL-triglyceride (TG) production rate and
      inhibiting the LPL-mediated VLDL-TG hydrolysis rate. Because apoC-III is a strong
      inhibitor of TG hydrolysis, we questioned whether Apoc3 deficiency might prevent
      the hyperlipidemia induced by apoE overexpression in vivo. Injection of 2 x 10(9)
      plaque-forming units of AdAPOE4 caused severe combined hyperlipidemia in Apoe-/-
      mice [TG from 0.7 +/- 0.2 to 57.2 +/- 6.7 mM; total cholesterol (TC) from 17.4 +/
      3.7 to 29.0 +/- 4.1 mM] that was confined to VLDL/intermediate density
      lipoprotein-sized lipoproteins. In contrast, Apoc3 deficiency resulted in a gene
      dose-dependent reduction of the apoE4-associated hyperlipidemia (TG from 57.2 +/-
      6.7 mM to 21.2 +/- 18.5 and 1.5 +/- 1.4 mM; TC from 29.0 +/- 4.1 to 16.4 +/- 9.8
      and 2.3 +/- 1.8 mM in Apoe-/-, Apoe-/-.Apoc3+/-, and Apoe-/-.Apoc3-/- mice,
      respectively). In both Apoe-/- mice and Apoe-/-.Apoc3-/- mice, injection of
      increasing doses of AdAPOE4 resulted in up to a 10-fold increased VLDL-TG
      production rate. However, Apoc3 deficiency resulted in a significant increase in
      the uptake of TG-derived fatty acids from VLDL-like emulsion particles by white
      adipose tissue, indicating enhanced LPL activity. In vitro experiments showed
      that apoC-III is a more specific inhibitor of LPL activity than is apoE. Thus,
      Apoc3 deficiency can prevent apoE-induced hyperlipidemia associated with a 10
      fold increased hepatic VLDL-TG production rate, most likely by alleviating the
      apoE-induced inhibition of VLDL-TG hydrolysis.

PMID- 15863839
TI  - Heterozygous mutation of ataxia-telangiectasia mutated gene aggravates
      hypercholesterolemia in apoE-deficient mice.
AB  - Individuals with a heterozygous mutation at the ataxia-telangiectasia mutated
      gene (ATM) have been reported to be predisposed to ischemic heart disease. This
      report examined for the first time the effect of a heterozygous ATM mutation
      (ATM(+)(/-)) on plasma lipid levels and atherosclerosis intensity using ATM(+/-),
      ATM(+)(/+) (wild type), ATM(+)(/+)/LDLR(-)(/-) (low density lipoprotein receptor
      knockout), ATM(+)(/-)/LDLR(-)(/-), ATM(+)(/+)/ApoE(-)(/-) (apolipoprotein E
      knockout), and ATM(+)(/-)/ApoE(-)(/-) mice. Our data demonstrated that the plasma
      cholesterol and triglyceride levels in ATM(+)(/-) and ATM(+)(/-)/LDLR(-)(/-) mice
      were approximately the same as those in ATM(+)(/+) and ATM(+)(/+)/LDLR(-)(/-)
      control mice, respectively. In contrast, the plasma cholesterol level was
      significantly higher in ATM(+)(/-)/ApoE(-)(/-) mice than in ATM(+)(/+)/ApoE(-)(/
      ) control mice. In addition, the ATM(+)(/-)/ApoE(-)(/-) mice showed higher plasma
      apoB-48 levels, slower clearance for plasma apoB-48-carrying lipoproteins, and
      more advanced atherosclerotic lesions in the aorta compared with the
      ATM(+)(/+)/ApoE(-)(/-) mice. These novel results suggest that the product of ATM
      is involved in an apoE-independent pathway for catabolism of apoB-48-carrying
      remnants; therefore, superimposition of a heterozygous ATM mutation onto an ApoE
      deficiency background reduces the clearance of apoB-48-carrying lipoproteins from
      the blood circulation and promotes the formation of atherosclerosis.

PMID- 15863840
TI  - An in situ perfusion protocol of rat epididymal adipose tissue useful in
      metabolic studies.
AB  - Experimental approaches involving the perfusion of tissues and organs offer the
      advantage of improved physiological relevance over the use of isolated tissues or
      cells while at the same time being much more controlled and tissue-specific than
      studies in vivo. Nevertheless, there have been few metabolic studies performed in
      perfused white adipose tissue, largely because of the difficulty of the surgical
      technique involved. Although some methods have been described, they are difficult
      to use as perfusion protocols and their reproducibility is poor. We have modified
      a rat perfusion method, based on a modification of the Ho and Meng technique, for
      use with epididymal white adipose tissue (eWAT), and we present it here as a
      protocol to be reproduced. We also offer surgical solutions for the most common
      variants of vessel distributions in rats. Using the protocol described here, the
      perfused adipose tissue is viable and metabolically active, as indicated by the
      maintenance of tissue ATP levels and adiponectin secretion and by endogenous
      lipolysis regulation. Moreover, there is a high level of lipoprotein lipase
      activity in the endothelium of the tissue, which is heparin-releasable. Thus,
      this method is a useful and reproducible tool that allows the perfusion of eWAT
      for use in metabolic studies.

PMID- 15863841
TI  - A novel method for the measurement of in vitro fatty acid 2-hydroxylase activity
      by gas chromatography-mass spectrometry.
AB  - Fatty acid 2-hydroxylase (FA2H), encoded by the FA2H gene, is an enzyme
      responsible for the de novo synthesis of sphingolipids containing 2-hydroxy fatty
      acids. 2-Hydroxy sphingolipids are highly abundant in the brain, as major myelin
      galactolipids (galactosylceramide and sulfatide) contain a uniquely high
      proportion ( approximately 50%) of 2-hydroxy fatty acids. Other tissues, such as
      epidermis, epithelia of the digestive tract, and certain cancers, also contain 2
      hydroxy sphingolipids. The physiological significance of the 2-hydroxylation on N
      acyl chains of subsets of sphingolipids is poorly understood. To study the roles
      of FA2H and 2-hydroxy sphingolipids in various tissues, we developed a highly
      sensitive in vitro FA2H assay. FA2H-dependent fatty acid 2-hydroxylation requires
      an electron transfer system, which was reconstituted in vitro with an NADPH
      regeneration system and purified NADPH:cytochrome P-450 reductase. A substrate
      [3,3,5,5-D(4)]tetracosanoic acid was solubilized in alpha-cyclodextrin solution,
      and the 2-hydroxylated product was quantified by gas chromatography-mass
      spectrometry after conversion to a trimethylsilyl ether derivative. When the
      microsomes of FA2H-transfected COS7 cells were incubated with the electron
      transfer system and deuterated tetracosanoic acid, deuterated 2-hydroxy
      tetracosanoic acid was formed in a time- and protein-dependent manner. With this
      method, FA2H activities were reproducibly measured in murine brains and tissue
      culture cell lines.

PMID- 15863842
TI  - Misidentification of prostamides as prostaglandins.
AB  - Prostaglandins and endogenous cannabinoid metabolites share the same lipid
      backbone with differing polar head groups at exactly the position through which a
      large molecule is attached to provide antigenicity and thus raise antisera.
      Hence, we hypothesized that antisera raised against prostaglandins linked to a
      large molecule such as BSA at the carboxyl functional group would also recognize
      endogenous cannabinoid metabolites and lead to highly misleading interpretations
      of data. We found major cross-reactivity of commercial antisera raised to
      prostaglandins with endocannabinoid metabolites. Furthermore, in a well
      characterized cell line (WISH) or primary amnion tissue explants, endocannabinoid
      treatment led to increased production of endocannabinoid metabolites as opposed
      to primary prostaglandins. This was apparent only after separation of products by
      thin-layer chromatography, because they measured as prostaglandins by
      radioimmunoassay. These findings have major implications for our interpretation
      of data in situations in which these prostaglandin-like molecules are formed, and
      they stress the need for chromatographic or spectrometric confirmation of
      prostaglandin production detected by antibody-based methods.

PMID- 15863843
TI  - The expression of p63 during epidermal remodeling in psoriasis.
AB  - Psoriasis is a skin disorder of chronic keratinization characterized by epidermal
      hyperplasia, hyperkeratosis, and inflammation. However, little is known about the
      mechanism (s) underlying the hyperplasia with elongated rete ridges
      characteristic of psoriasis. The p63 transcription factor, a homologue of the p53
      tumor suppressor, has been implicated in the maintenance of epidermal stem cells
      and the stratification of the epidermis. p63 is up-regulated in squamous cell
      carcinomas with anaplasia, suggesting that it is also associated with epidermal
      hyperplasia. In this study, we examined the expression of p63 in the remodeling
      of psoriatic epidermis. Lesional tissues from 17 psoriasis patients in various
      stages of plaque-type psoriasis and normal skin tissues from five healthy
      subjects were examined by immunohistochemistry using a monoclonal anti-p63
      antibody. Normal epidermis stained positively for p63 in the basal cell layer and
      in 2 to 4 layers of the spinous cell layer. p63 was positive in the thickened
      rete ridges of the epidermis even in early psoriatic lesions. As the epidermis
      elongated, p63-positive cells moved down and were localized in the lower parts of
      the rete ridges where keratinocytes densely proliferated. From these results, we
      suggest that p63 may be involved in the early stage of the remodeling process of
      the psoriatic epidermis as well as in the elongation of the rete ridges.

PMID- 15863844
TI  - Topical application of ketoconazole stimulates hair growth in C3H/HeN mice.
AB  - Ketoconazole (KCZ) is an imidazole anti-fungal agent that is also effective in
      topical applications for treating seborrheic dermatitis and dandruff. Recently,
      topical use of 2% KCZ shampoo has been reported to have had a clinically
      therapeutic effect on androgenetic alopecia. The present study was conducted with
      the purpose of quantitatively examining the stimulatory effect of KCZ on hair
      growth in a mouse model. Coat hairs on the dorsal skin of seven week-old male
      C3H/HeN mice were gently clipped, and either 2% KCZ solution in 95% ethanol or a
      vehicle solution was topically applied once daily for three weeks. The clipped
      area was photographed, and the ratio of re-grown coat area was then calculated.
      The results demonstrated that 2% KCZ had a macroscopically significant
      stimulatory effect compared with the vehicle group (p<0.01, n=10). Repeated
      experiments showed similar effects, confirming the efficacy of KCZ as a hair
      growth stimulant. Although the therapeutic mechanism of topical KCZ for hair
      growth is unclear, our results suggest that topical applications of the substance
      are useful for treating seborrheic dermatitis accompanied by hair regression or
      male pattern hair loss.

PMID- 15863845
TI  - Prevalence of atopic dermatitis and serum IgE values in nursery school children
      in Ishigaki Island, Okinawa, Japan.
AB  - There have been many studies of the prevalence of atopic dermatitis (AD), but few
      population-based epidemiologic studies measure the prevalence in Japan among
      children aged 5 years and younger. We examined the prevalence of AD, serum total
      IgE levels and specific IgE antibodies to 10 common allergens among children in
      Ishigaki Island, Okinawa, Japan in 2001. We also obtained information on the
      predictability of the U.K. Working Party diagnostic questionnaire criteria for AD
      in this population. Five hundred and sixty five children aged 5 years and younger
      were enrolled in this study with informed consent from their parents. The
      questionnaire of the U.K. Working Party diagnostic criteria for AD was translated
      into Japanese, and the parents completed the questionnaire sheet. Physical
      examination and blood sampling were done for all children. Thirty-nine out of the
      565 (6.9%) children were diagnosed with AD by physical examination. The total and
      specific IgE levels were significantly higher in the children with AD than in
      those without AD. High levels of total IgE were found in 33.3% of the children
      with AD. A specific IgE to one or more allergens was detected in 64.1% of
      children with AD. However, a substantial population of children without AD also
      had high levels of total IgE (12.7%) and a specific IgE to one or more allergens
      (30.2%), and the increment of total and specific IgE levels was significantly
      associated with age. The percentage of positive answers to the questionnaire of
      the U.K. Working Party diagnostic criteria for AD was significantly higher in
      children with AD (59.0%) than in children without AD (5.3%) (P<0.0001). Its
      specificity was 94.7%. The false negative rate was 41%. In conclusion, the
      prevalence of AD was relatively low in children in Ishigaki Island. High levels
      of total IgE were found in only one third of children with AD under 5 years of
      age. The Japanese translated form of the questionnaire of the U.K. Working Party
      diagnostic criteria for AD should be refined to improve its sensitivity.

PMID- 15863846
TI  - Biotin deficiency in an infant fed with amino acid formula.
AB  - Biotin deficiency is rarely encountered in an infant on weaning from breast and
      formula feeding. It is characterized by alopecia and scaly, erythematous
      dermatitis distributed around the body orifices. We report a 5-month-old Japanese
      infant with typical skin lesions who had been diagnosed as a neonate with
      dyspepsia and fed only an amino acid formula. Serum and urine levels of biotin
      were below the normal range, but zinc and biotinidase were within normal range.
      Urinary excretion of 3-methylcrotonylglycine, 3-hydroxyisovaleric acid, and
      methylcitric acid was significantly elevated. Daily oral supplementation with 1
      mg of biotin resulted in dramatic improvement of the periorificial dermatitis and
      hair growth together with a complete disappearance of the organic aciduria. Our
      case shows that the characteristic skin manifestations are the most important
      clue to the diagnosis of biotin deficiency and demonstrated that urinary
      excretion of biotin and organic aciduria, rather than the serum concentration of
      biotin, are the sensitive indicators for evaluating the patient's status of
      biotin deficiency.

PMID- 15863847
TI  - Clinical results of OK-432 injection therapy for ganglions.
AB  - We performed a study of intralesional OK-432 injection therapy for the non
      surgical treatment of ganglions. OK-432 is an agent made from penicillin-killed
      and lyophilized preparations of a low-virulence strain of group A streptococcus
      pyogenes, which has been developed as an immune-augmentation agent for cancer
      therapy. Derived from an extract of bacterial culture it, induces an
      immunological response and causes local inflammation and subsequent tissue
      shrinkage following intralesional injection. After skin anesthesia and aspiration
      of the ganglion contents, OK-432 was injected into the ganglion cavity. When the
      ganglion recurred, this procedure was repeated usually up to a total of three
      times. Clinical evaluations six months after the last injection were: 56.6%
      complete cure, 35.3% incomplete cure with size reduced, 7.5% no change.
      Complications were as follows. There were no cases of shock. High fever was seen
      in five patients (9.4%); two patients suffered a high fever up to 39.0 degrees C
      for one day, and the others had fevers from 1 to 3 days. Thirty-two patients
      (60.4%) complained of local swelling that persisted for 1 to 7 days, and 11
      (20.8%) complained of continuous pain for 1 to 3 days. Intralesional OK-432
      injection therapy is thought to be a safe and convenient alternative to surgical
      treatment.

PMID- 15863848
TI  - Sensitivity and specificity of different diagnostic criteria for Behcet's disease
      in a group of Turkish patients.
AB  - Because there are no diagnostic laboratory tests or histopathologic findings, the
      diagnosis of Behcet's disease (BD) is based on clinical criteria. Various
      diagnostic criteria have been proposed. In this study, we assessed the
      sensitivity, specificity and the relative value of the Mason & Barnes, Japanese,
      Hamza, O'Duffy, Cheng & Zhang, Dilsen and International Study Group (ISG)
      criteria. Two hundred twenty-eight patients with Behcet's disease diagnosed
      according to either O'Duffy's or ISG criteria and 89 control patients with a
      variety of connective tissue diseases, including sarcoidosis, uveitis, erythema
      nodosum, and granulomatous intestinal disease, were evaluated. ISG and Hamza
      criteria showed the highest specificity (100%) in discriminating control subjects
      from the entire cohort. The highest sensitivity value (100%) was found in the
      Cheng & Zang criteria, which were found to be the most sensitive but the least
      specific (74.2%). The Hamza criteria had the highest relative value (sensitivity
      plus specificity) (198.2). Dilsen (196.9) and ISG (196.5) criteria also had high
      relative values. In this study, Hamza, Dilsen, and ISG criteria performed quite
      well in diagnosing BD in our country compared to the other criteria sets.

PMID- 15863849
TI  - Cutaneous mucormycosis in a patient with acute lymphocytic leukemia.
AB  - We describe a patient with invasive necrotizing cutaneous mucormycosis caused by
      Rhizopus oryzae. The patient, who had been suffering from acute lymphocytic
      leukemia (ALL) for eight months, had erythema and necrosis surrounded by swelling
      on the dorsum of his left hand. Debridement was performed, and microscopic
      examination of the obtained specimens revealed mucormycosis. Because amphotericin
      B was ineffective, amputation at the left shoulder joint was performed. Bone
      marrow transplantation (BMT) was successfully carried out 22 days after surgery.
      However, the patient died 162 days after the BMT due to progression of the ALL.
      Patients such as the present one should be evaluated promptly by tissue biopsy
      and appropriate cultures, so that vigorous treatment can be started without
      delay. Where necessary, amputation should be performed.

PMID- 15863850
TI  - Drug-induced hypersensitivity syndrome due to mexiletine associated with human
      herpes virus 6 and cytomegalovirus reactivation.
AB  - A 66-year-old man developed a fever of 38 degrees C and generalized pruritic rash
      about one month after mexiletine hydrochloride administration for ventricular
      tachycardia. The rash appeared as edematous erythema and papules with purpura on
      the lower extremities. Liver dysfunction, leukocytosis, and atypical lymphocytes
      were also present. Elevated antibody titer against human herpes virus 6 (HHV-6)
      was detected during the course of the disease (1:20 -> 1:640). The patient was
      diagnosed as having drug-induced hypersensitivity syndrome (DIHS) due to
      mexiletine. Discontinuation of the mexiletine administration and systemic
      corticosteroid treatment led to a temporary improvement, but tapering the
      corticosteroid dose twice led to recrudescence. Simultaneous with the
      recrudescence, elevated antibody titers against HHV-6 and cytomegalovirus were
      detected, as well as viral DNA in the blood, suggesting that these two viruses
      may have been involved in the recrudescence. The patient died of myocarditis,
      most likely related to cytomegalovirus. Our case indicates that, in addition to
      HHV-6, other herpes viruses such as cytomegalovirus can be reactivated in DIHS
      and may modify the clinical disease activity.

PMID- 15863851
TI  - Two cases of dystrophic calcinosis cutis in burn scars.
AB  - Dystrophic calcinosis cutis is defined as the abnormal deposition of insoluble
      calcium salts in dead or degenerated cutaneous tissues in the absence of abnormal
      serum calcium or phosphate concentrations. Although dystrophic calcification can
      occur in various diseases, its occurrence on a burn scar has rarely been reported
      in the dermatologic literature. Herein we describe two patients who presented
      with a solitary non-healing ulcer in a postburn scar, with histopathologic
      evidence of calcium deposition in the dermis.

PMID- 15863852
TI  - A case of hypereosinophilic syndrome.
AB  - A 22-year-old man developed papules on his legs in November of 2001, which then
      spread to cover almost his entire body. He was treated with a topical steroid and
      PUVA therapy at another hospital. The symptoms showed no improvement, and, in
      February of 2002, he came to our hospital. Examination revealed
      hypereosinophilia, and, because he had symptoms of organ involvement by the
      heart, lung, and inguinal lymph nodes as well as the skin, we diagnosed him with
      idiopathic hypereosinophilic syndrome (HES). The patient was treated with oral
      prednisolone at a dose of 60 mg/day, and his cutaneous lesions and other organ
      symptoms improved.

PMID- 15863853
TI  - Relapse of dermatomyositis after 10 years in remission following curative
      surgical treatment of lung cancer.
AB  - A 55-year-old woman with dermatomyositis and small cell lung cancer was
      successfully treated with surgery followed by combination chemotherapy in 1987.
      She had been in remission without further immunosuppressive therapy for 10 years.
      However, myositis with cutaneous manifestations specific for dermatomyositis
      relapsed when the patient was 69 years old. Intensive examinations revealed no
      neoplasm, and she responded to a moderate dose of systemic corticosteroids. This
      case suggests a long-lasting autoimmune abnormality in dermatomyositis and that a
      neoplasm is an important factor in eliciting an occult dermatomyositis.

PMID- 15863854
TI  - Cholesterol crystal embolization: skin manifestation, gastrointestinal and
      central nervous symptom treated with corticosteroid.
AB  - Cholesterol crystal embolization (CCE) is characterized by tissue ischemia
      secondary to occlusion of small arteries. It may occur spontaneously but more
      often follows radiological interventional procedures or vascular surgery. This
      systemic disease affects multiple organs, including skin, kidney, brain, eye, and
      gastrointestinal tract. We reported a Japanese male CCE patient with cutaneous
      manifestations of livedo reticularis, diarrhea, clouding of consciousness, and
      acute renal failure. Histopathological examination demonstrated multiple biconvex
      clefts in a vessel of the subcutis. Corticosteroid administration improved his
      consciousness, diarrhea and skin lesions. Awareness of the skin manifestations of
      CCE is essential for dermatologists to make an early diagnosis and prescribe
      appropriate treatment.

PMID- 15863855
TI  - A case of cytomegalovirus colitis following immunosuppressive treatment for
      pyoderma gangrenosum.
AB  - We report a case of pyoderma gangrenosum (PG) complicated by cytomegalovirus
      (CMV)-induced colitis. A 79-year-old woman with PG was treated with
      corticosteroid and cyclosporin. She had blood in her stool and advancing anemia
      during the treatment. A colonoscopic biopsy specimen from the colon revealed
      typical CMV-infected cells with CMV inclusions confirmed by immunohistochemistry.
      Furthermore, there were many CMV-antigen-positive leukocytes, suggesting an
      active CMV infection, which is serious in compromised hosts. Although ulcerative
      colitis and Crohn's disease are well known as complications of PG, CMV
      enterocolitis should be considered in the differential diagnosis of enterocolitis
      in immunocompromised patients.

PMID- 15863856
TI  - Sclerosing segmental neurofibromatosis.
AB  - Segmental neurofibromatosis is a rare disorder characterized by cafe-au-lait
      macules and/or neurofibromas limited to a single body segment. The neurofibromas
      in segmental neurofibromatosis are usually soft, non-tender nodules as in other
      types of neurofibromatosis. Histopathologically, they are usually non
      encapsulated, loosely textured dermal tumors. We report a case of sclerosing
      segmental neurofibromatosis, in which the patient presented with several grouped,
      erythematous to brownish, firm tender nodules on the left side of the posterior
      neck. Histopathologically, the stroma was mostly very fibrotic, especially around
      hair follicles, in addition to the usual features of neurofibroma. The atypical
      clinical feature, hardness, and tenderness of the lesions may be associated with
      the fibrosis.

PMID- 15863857
TI  - Orf and religious practices.

PMID- 15863858
TI  - Giant steatocystoma simplex.

PMID- 15863859
TI  - Giant annular lichen planus: wolf's isotopic response.

PMID- 15863860
TI  - Psychosomatic analysis of atopic dermatitis using a psychological test.
AB  - In patients with atopic dermatitis (AD), psychosomatic factors are important
      elements in treating the condition. In this study, we surveyed 51 outpatients
      with AD who consulted the Department of Dermatology of Fujita Health University
      Hospital using a questionnaire involving present illness/treatment history
      regarding AD to analyze psychosomatic factors. The severity of AD was evaluated
      using the severity classification described by Yoshiike et al. Four psychological
      tests were used to examine depression, anxiety, personality, and upbringing
      experiences during childhood. Beck Depression Inventory (BDI) was used as a scale
      for depression, Self-rating Anxiety Scale (SAS) as a scale for anxiety, the
      Temperament and Character Inventory (TCI) as a scale for the personality
      tendency, and the Parental Bonding Instrument (PBI) as a scale for upbringing
      experiences during childhood. The BDI and SAS scores were high in the severe AD
      group. Among patients with the same grade of AD, the BDI and SAS scores were
      higher in the low IgE RIST group. In the patients with AD, the BDI scores were
      significantly higher than those in the healthy controls (P<0.05). In clinical
      practice, the treatment of AD should include psychosomatic approaches.

PMID- 15863861
TI  - Benzoyl peroxide, adapalene, and their combination in the treatment of acne
      vulgaris.
AB  - Benzoyl peroxide and adapalene are among the most effective topical agents used
      in the treatment of acne. We planned an open-labeled, prospective study to
      compare the effects and side effects of these two drugs alone and in combination
      in the treatment of acne vulgaris. One hundred and five consecutive patients (30
      men and 75 women) with acne vulgaris were included in this study. The patients
      were randomly divided into three groups with 35 patients in each. The groups were
      randomly assigned to 0.1% adapalene gel, 5% benzoyl peroxide lotion, or
      combination of 0.1% adapalene gel +5% benzoyl peroxide treatment. Acne lesions
      were classified as noninflammatory (open and closed comedones) and inflammatory
      (papule, pustule, nodule, cyst), and the lesions on the face were counted before
      the therapy, during the control visits, and after the treatment. Erythema,
      dryness, burning, and other side effects were recorded during the treatment. The
      mean age of the patients was 18.44 +/- 3.75 years. Eight patients were excluded
      because of noncompliance with the treatment regimen or the follow-up schedule,
      and four patients were excluded due to allergic contact dermatitis. The study
      revealed that all three therapy protocols were effective in treating
      noninflammatory and inflammatory lesions in acne vulgaris (p<0.05) and that there
      was no significant difference between the groups in efficacy or side effects
      (p>0.05). Adapalene and benzoyl peroxide are effective and well tolerated agents
      for acne vulgaris; combination therapy has no superiority over adapalene or
      benzoyl peroxide alone.

PMID- 15863862
TI  - Ocular surface disorders and tear function changes in nodulo-cystic acne.
AB  - The aim of this study was to investigate the ocular surface disorders and tear
      function changes in patients with nodulo-cystic acne. Eighty-seven patients with
      nodulo-cystic acne vulgaris and 50 healthy subjects were included in the study.
      All subjects underwent full ocular examinations. Subjective ocular complaints
      were recorded. Corneal staining with fluorescein, tear film break-up time (BUT),
      and Schirmer test were applied. Abnormal tear film BUT and abnormal Schirmer
      scores were significantly more common in the acne group than in the control
      group. The tear film BUT was abnormal in 18 (20.7%) cases in the patient group
      and in 2 (4%) subjects in the control group (p=0.007). The mean Schirmer score
      was abnormal in 7 (8%) and decreased in 18 (20.7%) acne patients, and it was
      decreased in only 3 (6%) control subjects (p=0.005). Corneal punctuate epithelial
      erosions were detected in 3 (3.4%) acne patients, but not any of the control
      subjects. However, the difference between the groups was not statistically
      significant (p=0.184). Subjective ocular complaints were present in 28 cases
      (32.2%) in the patient group. Five (10%) subjects in the control group had such
      complaints (p=0.003). Tear function tests are also significantly altered in
      patients with nodulo-cystic acne. Our data suggest that severe acne patients
      should be referred to an ophthalmologist.

PMID- 15863863
TI  - Autoantibodies other than antineutrophil cytoplasmic antibodies are not positive
      in patients with psoriasis vulgaris.
AB  - There is a great deal of evidences that a link may exist between psoriasis and
      autoimmunity. In this study, thirty-six patients with psoriasis vulgaris and
      twenty healthy controls were screened for antinuclear antibody (ANA), anti-ds-DNA
      antibodies, anti-SSA (anti-Ro), anti-SSB (anti-La), anti-Scl-70, anti-Jo-1,
      rheumatoid factor (RF), C3 and C4 levels, IgG and IgM anti-cardiolipin antibodies
      (aCL) and anti-neutrophil cytoplasmic antibodies (pANCA and cANCA) in order to
      determine the role of autoimmunity in the pathogenesis. In addition, the MPO-ANCA
      test was performed on pANCA-positive patients. In ANA screening, one patient
      showed 1/80 granular positivity. No positive results were obtained from either
      the study or control groups for anti-dsDNA, anti-SSA, anti-SSB, anti-Scl-70, or
      anti-Jo-1 determinations. For RF, 5.8% of the patients had positive values. Both
      C3 and C4 levels were found to be significantly elevated in psoriasis patients
      compared to healthy controls (p<0.001). IgG-aCL and IgM-aCL positivity was not
      significantly different between the two group. pANCA was positive in 33.3% of the
      patients and a significant difference was observed between study and control
      groups (p<0.05). MPO-ANCA was negative in all the pANCA-positive patients. In
      conclusion, only serum C3 and C4 levels and pANCA determinations showed
      significant differences when compared to healthy controls. Our findings may be
      evidence of associations between autoimmunity and psoriasis vulgaris. However,
      more detailed studies in this field need to be done to determine the relationship
      between them.

PMID- 15863864
TI  - Simultaneous onset of pemphigus vulgaris in two Turkish siblings.
AB  - The etiology of pemphigus vulgaris is still unknown. Reported familial cases are
      indicators of a genetic aspect of the disease. We report a brother and sister
      with simultaneous onset of pemphigus vulgaris. The class II antigens, HLA DRB1*04
      and DQB1*03 were detected in both patients. The oral mucosa was affected in one
      them. Elevation of transaminase levels due to azathioprine therapy was observed
      in these two cases.

PMID- 15863865
TI  - Chronic superficial pyoderma of the face: an unusual male case of rosacea
      fulminans.
AB  - A 62-year-old Japanese male developed acneiform papules on the face in November
      of 2002. The eruptions progressed to exudative erythema with central necrosis,
      and then to thick-crusted superficial abscesses in a short period. The shallow
      ulcers exposed by removal of the crusts and abscesses immediately re-epithelized
      without leaving scars. The histology of the eruption was a dense infiltration of
      neutrophils associated with granulomatous changes in the upper to middle dermis.
      Histology of the tiny white particles in the abscess showed an irregularly
      proliferated mass of keratinocytes including accumulated neutrophils. The skin
      lesions resisted intravenous injection of antibiotics but responded to systemic
      administration of a corticosteroid agent. Colchicine did not work well, but the
      additional administration of etretinate was effective. The patient is currently
      receiving combined therapy with prednisolone and etretinate, but eruptions are
      still episodically observed. We diagnosed this case as an unusual male case of
      rosacea fulminans.

PMID- 15863866
TI  - Pyoderma gangrenosum associated with nasal septal perforation, oropharyngeal
      ulcers and IgA paraproteinemia.
AB  - We report a case of pyoderma gangrenosum (PG) associated with nasal septal
      perforation, pharyngeal ulcers and IgA paraproteinemia. A 28-year-old woman first
      developed painful undermined ulcers on her perianal, inguinal and axillary areas
      when she was 22 years old. Histological findings from the cutaneous ulcers showed
      dermal and epidermal infiltrate of neutrophils, which was compatible with PG.
      Laboratory examinations did not detect any associations of systemic diseases
      other than polyclonal IgA paraproteinemia. Nasal fiberscopy revealed septal
      perforation and multiple ulcers on her pharynx. The biopsy specimen from the
      pharyngeal ulcers showed a polymorphous cellular infiltrate without necrotizing
      vasculitis or granuloma. However, there were no atypical lymphocytes that are
      typically seen in nasal NK/T lymphoma. By immunohistochemical analysis, the
      infiltrated lymphocytes were proved to be T cells and Epstein-Barr virus encoded
      RNA (EBER) was not detected. No pulmonary or renal lesions resembling Wegener's
      granulomatosis were found. Taken together, the nasal septal perforation was
      considered as nasal involvement of PG.

PMID- 15863867
TI  - Topical tacrolimus therapy for pyoderma gangrenosum.
AB  - Pyoderma gangrenosum (PG) is a type of neutrophilic disorder with a chronic
      clinical course. Immunosuppressive agents have been used for its management.
      Among them, corticosteroid is known as the most effective. However, other
      immunosuppressants including cyclosporine A have been selected for patients with
      PG who were refractory to systemic steroids. Herein we report a case of PG
      resistant to systemic steroids, who was successfully treated with topical
      tacrolimus. A fifty-four year-old male had a 14-year history of PG. In 2002,
      necrotic ulcers appeared on his right leg that were refractory to oral
      prednisolone (30 mg/day). The application of topical tacrolimus to the border of
      the ulcers hastened epithelization of the ulcers and allowed for reduction of the
      oral prednisolone. Topical tacrolimus therapy may be an effective alternative for
      PG when the lesion is poorly controlled by corticosteroid.

PMID- 15863868
TI  - Extra nodal NK/T-cell lymphoma nasal type that responded to DeVIC combination
      chemotherapy.
AB  - We report a 76-year-old woman with extra nodal NK/T-cell lymphoma nasal type
      (ENKL). She had large tumors on her left leg with inguinal lymphadenopathy and
      gastric tumors. The tumor cells showed angiocentric growth with necrosis.
      Immunohistologically, the tumor cells from the skin lesion expressed CD2,
      cytoplasmic CD3, CD56, and T-cell intracellular antigen-1 (TIA-1), but not
      surface CD3, CD19, and TdT. The gastric tumor cell, also expressed cytoplasmic
      CD3, CD45RO and CD56. She was diagnosed as having ENKL (stage IV of Ann Arbor).
      The tumors responded remarkably well to radiation therapy followed by multi-drug
      resistance independent DeVIC (carboplatin, etoposide, ifosfamide, and
      dexamethasone) combination therapy. After two series of this therapy, no tumors
      were detected in clinical, histopathological, endoscope and computerized tomogram
      (CT) examinations. However, she suddenly died of brain stem metastasis three
      months later. Although there may be a limitation of effects on metastasis of
      tumors in the central nervous system, radiation and DeVIC combination therapy is
      a potent therapeutic method for ENKL.

PMID- 15863869
TI  - Bowen's disease involving the urethra.
AB  - Bowen's disease developing on mucous or mucocutaneous regions is clinically
      called erythroplasia of Queyrat. We report herein a 56-year-old male with Bowen's
      disease extending from the penis shaft to the glans penis, and urethral meatus.
      Physical examination revealed bright red velvety plaques on the prepuce and glans
      penis and an irregularly pigmented scaly lesion on the dorsum of his penis shaft.
      Histopathological findings of both lesions were compatible with those of Bowen's
      disease, supporting the concept that erythroplasia of Queyrat and Bowen's disease
      should be regarded as one clinicopathologic entity. A partial penectomy was
      finally performed, because tumor cells were pathologically observed in the mucous
      epithelium of the urethra. Although several therapeutic modalities exist for
      Bowen's disease on the external genitalia, treatment options are limited when
      Bowen's disease extends to the urethral meatus. We discussed the recent
      therapeutic modalities in genital Bowen's disease.

PMID- 15863870
TI  - A case of congenital soft tissue chondroma.
AB  - Soft tissue chondromas are rare benign tumors unrelated to bone that arise
      primarily in the distal extremities, especially in the fingers of middle-aged
      adults. We report an extremely rare case of congenital soft tissue chondroma,
      arising in the left great toe of a new-born infant. The present case is, to our
      knowledge, the first to be described in the dermatologic literature and the
      second reported case of congenital soft tissue chondroma.

PMID- 15863871
TI  - Lues maligna in a chronic alcoholic patient.
AB  - Lues maligna, which is characterized by noduloulcerative lesions, is a rare form
      of secondary syphilis. It is mainly seen in either HIV-infected or malnourished
      patients suffering from a depression in immunity. We presented a chronic
      alcoholic, HIV negative male patient with noduloulcerative lesions diagnosed as
      lues maligna based on his skin eruptions, results of serologic tests, and,
      histopathologic findings. We believe that chronic alcoholism could be the cause
      of immunosuppression in our case and wanted to emphasize the possibility of an
      association between lues maligna and chronic alcoholism.

PMID- 15863872
TI  - Unilateral xanthelasma forming a kissing-like lesion.
AB  - Xanthelasma is a common cutaneous xanthomatosis which occurs usually on the
      medial canthus in the upper or inferior palpebra. We describe a rare case of
      kissing xanthelasma which was unilateral at early onset.

PMID- 15863873
TI  - Hailey-Hailey disease exacerbated by scabies.

PMID- 15863874
TI  - Discoid lupus erythematosus exacerbated by radiation therapy.

PMID- 15863875
TI  - A long-lasting scrofuloderma on the back of the right hand.

PMID- 15863876
TI  - Primary cutaneous nocardiosis due to Nocardia brasiliensis in an immunocompetent
      patient.

PMID- 15863877
TI  - Anti-fungal activity of sulfamethoxazole toward Aspergillus species.
AB  - Invasive mycosis has significantly increased in frequency among immunocompromised
      hosts leading to excessive morbidity and mortality. The combination of
      sulfamethoxazole (SMX) and trimethoprim (TMP) has been used extensively for the
      treatment and prophylaxis of infections by various microbes. The purpose of this
      study is to estimate the anti-fungal activity of SMX-TMP and examine the
      mechanism of activity. To investigate the antimicrobial activity of SMX-TMP in
      vitro, a mixture of SMX and TMP at 5:1 was serially diluted and added to potato
      dextrose agar medium or C-limiting agar medium. Aspergillus species were
      inoculated on the medium plate with SMX-TMP. The growth of A. fumigatus and A.
      oryzae was inhibited by addition of SMX-TMP. The anti-Aspergillus effect depended
      on not TMP but SMX and that was inhibited by p-aminobenzoic acid (PABA). A. niger
      was not sensitive against SMX-TMP in PDA medium, but sensitive in C-limiting
      medium. Those results showed that the activity depends on culture medium.
      Furthermore, addition of human serum did not influence the activity of SMX. The
      finding in this study suggested that SMX might be effective against Aspergillus
      species in clinical practice and prophylaxis treatment.

PMID- 15863878
TI  - Involvement of mitochondrial peroxynitrite in nitric oxide-induced glutathione
      synthesis.
AB  - Cells respond to oxidative stress including nitric oxide (NO) by increasing
      cellular glutathione concentration, as a part of adaptive response against
      oxidative injury. To elucidate the mechanism by which NO induces glutathione we
      investigated the reactive oxygen species (ROS) generated in the cell. Treatment
      of RAW264.7 cells with NO donor, sodium nitroprusside (SNP), resulted in a
      temporary increase in glutathione in a dose-dependent manner, which peaked
      between 6 h and 12 h after treatment, whereas expression of gamma
      glutamylcysteine synthetase (gamma-GCS) mRNA peaked around 3 h after treatment.
      The increase was inhibited by NO scavengers, oxyhemoglobin and carboxyl-2-(4
      carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). N-Acetyl-L
      cysteine (NAC) also reduced the increase in glutathione to some extent, whereas
      both peroxynitrite scavenger ebselen and hydroxyl radical scavenger DMSO
      inhibited the increase in glutathione in a dose-dependent manner and complete
      inhibition was observed. Hydrogen peroxide exogenously added to the cell did not
      increase either glutathione or gamma-GCS expression at any concentration,
      indicating that involvement of hydrogen peroxide is not likely. Flow cytometric
      analysis showed that SNP induced a marked dose-dependent increase in Rhodamine123
      fluorescence, which was completely inhibited by ebselen in a dose-dependent
      manner, whereas, little increase in 2',7'-dichlorofluorescin (DCF) fluorescence
      was observed. Generation of peroxynitrite in mitochondria by SNP was confirmed by
      elevated level of nitrotyrosine in a mitochondria fraction isolated from SNP
      treated cells, and the elevation was completely inhibited by ebselen as well.
      These results suggest that induction of glutathione (GSH) synthesis by SNP
      treatment is mediated by peroxynitrite generated in mitochondria.

PMID- 15863879
TI  - Inhibitory effects of fungal bis(naphtho-gamma-pyrone) derivatives on nitric
      oxide production by a murine macrophage-like cell line, RAW 264.7, activated by
      lipopolysaccharide and interferon-gamma.
AB  - Inhibitory effects of six fungal bis(naphtho-gamma-pyrone) derivatives on nitric
      oxide (NO) production by a murine macrophage-like cell line, RAW 264.7, which was
      activated by lipopolysaccharide and interferon-gamma were examined. Among these
      derivatives, chaetochromin (4) (IC(50): 0.8 microM), cephalochromin (1) (IC(50)
      1.5 microM), and dihydroisoustilaginoidin A (6) (IC(50) 2.8 microM) exhibited
      strong inhibitory activity. The bis(naphtho-gamma-pyrone) derivatives did not
      affect the enzyme activity of inducible nitric oxide synthase (iNOS). However,
      these derivatives significantly reduced both the induction of iNOS protein and
      iNOS mRNA expression. These results suggest that the bis(naphtho-gamma-pyrone)
      derivatives have the pharmacologic ability to suppress NO production by activated
      macrophages.

PMID- 15863880
TI  - Molecular and sugar-binding heterogeneity of C-type lectins from Osmerus
      (Spirinchus) lanceolatus eggs.
AB  - Two C-type lectins (OLLafs and OLLafl) were isolated from Osmerus (Spirinchus)
      lanceolatus eggs using asialofetuin-Sepharose column. OLLafs and OLLafl were
      eluted with 0.2 M sucrose and 0.2 M lactose from the same column, respectively.
      OLLafl has been estimated to be a heterodimeric protein composed of H- and L
      subunit and involved C-type lectin like domain (CTLD). In this study we revealed
      that OLLafs was a homodimeric protein composed of L-subunit of OLLafl. Although
      adding EDTA diminished the hemagglutinating activity of OLLafs, the activity of
      OLLafl was not influenced. Recombinant lectins (rOLLafl-H and -L) and mutant
      lectins replaced Cys(123, 131 and 136) with Ala (mOLLafl-L(123, 131 and 136))
      were established. The activity of mOLLafl-L(136) was comparable to rOLLafl-L, and
      rOLLafl-H was 15 times lower than rOLLafl-L. On the other hand, the activity of
      mOLLafl-L(123) and mOLLafl-L(131) were lower than that of rOLLafl-H. Therefore,
      Cys(136) may not participate in hemagglutinating activity of rOLLafl-L. In
      contrast, Cys(123) and Cys(131) may partially contribute this activity. Although
      hemagglutination inhibition profiles of rOLLafl-L, rOLLafl-H and mOLLafl-L(136)
      were similar, m-OLLafl-L(131)-induced hemagglutination was not inhibited by any
      sugars tested even at a concentration of 150 mM. Then, Cys(131) may directly
      contribute to the sugar-binding capacity of OLLafl. Affinities of mOLLafl-L(123)
      for these sugars were lower than the others. These results suggest that Cys(136)
      might contribute to the intermolecular disulfide bond in the rOLLafl-L dimer, and
      that the intramolecular disulfide bond concerning Cys(131) might important for
      lectin activity.

PMID- 15863881
TI  - 2-amino-phenoxazine-3-one attenuates glucose-induced augmentation of embryonic
      form of myosin heavy chain, endothelin-1 and plasminogen activator inhibitor-1 in
      human umbilical vein endothelial cells.
AB  - The aim of this study was to investigate the changes in mRNA level of embryonic
      form of myosin heavy chain (SMemb), endothelin-1 (ET-1) and plasminogen activator
      inhibitor-1 (PAI-1), which are considered to be involved in the angiogenesis and
      atherosclerosis in diabetic blood vessels, in human umbilical vein endothelial
      cells (HUVECs) caused by high ambient glucose, and the effects of 2
      aminophenoxazine-3-one (Phx-3), which was produced by the reaction of bovine
      hemoglobin with o-aminophenol, on them. The mRNA level of SMemb, ET-1 and PAI-1
      and the level of SMemb protein were extensively upregulated in HUVECs treated
      with high concentration of glucose (15 mM), compared with those in the cells with
      normal concentration of glucose (5 mM). The migration activity of HUVECs
      evaluated by the cell migration assay was accelerated by 15 mM glucose. When 10
      microM Phx-3, at the concentration of which the proliferation of HUVECs was not
      affected, was administered to HUVECs with 15 mM glucose, the mRNA level of SMemb,
      ET-1 and PAI-1 and the level of SMemb protein were significantly downregulated to
      the normal levels in the cells. However, when 10 microM Phx-3 was administered to
      HUVECs with 5 mM of glucose, the mRNA level of SMemb, ET-1 and PAI-1 and the
      level of SMemb protein were not affected. The migration activity of HUVECs, which
      was accelerated by high glucose, was reversed by 10 microM Phx-3. The present
      results suggest that Phx-3 may be a drug to prevent the high glucose-associated
      endothelial damage, vascular angiogenesis in diabetic patients, by inhibiting the
      expression of angiogenic factors, such as SMemb, ET-1 and PAI-1, in the
      endothelial cells.

PMID- 15863882
TI  - The essential oils from Zanthoxylum schinifolium pericarp induce apoptosis of
      HepG2 human hepatoma cells through increased production of reactive oxygen
      species.
AB  - The volatile extract from dried pericarp of Zanthoxylum schinifolium that was
      obtained by simultaneous distillation with dichloromethane and water was composed
      of 29.9% geranyl acetate, 15.8% citronella, 15.4% sabinene and the minor volatile
      components included beta-myrcene, linalool, (-)-isopulegol, citronellyl acetate,
      1,4-dimethyl pyrazole, alpha-terpinene, 3-methyl-6-(1-methylethyl)-2-cyclo-hexene
      1-o1 and trans-geraniol. The volatile extract decreased the cell viability and
      induced apoptotic death in HepG2 human hepatoma cells in a concentration- and
      time-related manner. In addition, the volatile extract increased the production
      of reactive oxygen species in a dose-dependent manner. Pretreatment of the cells
      with Trolox, a well-known antioxidant, significantly suppressed the generation of
      reactive oxygen species and cell death induced by the extract. However, caspase-3
      activity was not changed in the extract-treated cells, suggesting that the
      extract-induced apoptosis of HepG2 cells is caspase-3 independent. Furthermore,
      in nude mice inoculated with Huh-7 human hepatoma cells, the extract
      significantly inhibited tumor development. These results suggest that the
      volatile extract from Zanthoxylum schinifolium pericarpium is a good candidate
      for hepatocellular carcinoma (HCC) therapy and that reactive oxygen species are
      the key signaling molecules in the volatile extract-induced cell death in HepG2
      cells.

PMID- 15863883
TI  - Hypnotic activities of chamomile and passiflora extracts in sleep-disturbed rats.
AB  - In the present study, we investigated hypnotic activities of chamomile and
      passiflora extracts using sleep-disturbed model rats. A significant decrease in
      sleep latency was observed with chamomile extract at a dose of 300 mg/kg, while
      passiflora extract showed no effects on sleep latency even at a dose of 3000
      mg/kg. No significant effects were observed with both herbal extracts on total
      times of wakefulness, non-rapid eye movement (non-REM) sleep and REM sleep.
      Flumazenil, a benzodiazepine receptor antagonist, at a dose of 3 mg/kg showed a
      significant antagonistic effect on the shortening in sleep latency induced by
      chamomile extract. No significant effects were observed with chamomile and
      passiflora extracts on delta activity during non-REM sleep. In conclusion,
      chamomile extract is a herb having benzodiazepine-like hypnotic activity.

PMID- 15863884
TI  - Antianginal effects of lercanidipine on the vasopressin or methacholine induced
      anginal model in rats.
AB  - The antianginal effects of lercanidipine, a newly synthesized 1,4-dihydropyridine
      derivative calcium channel antagonist, were evaluated in experimental angina
      model rats and the effects were compared with those of nifedipine, benidipine and
      amlodipine. In the vasopressin-induced angina model, intravenous administration
      of lercanidipine dose-dependently suppressed vasopressin-induced ST-depression.
      Amlodipine barely suppressed it, while benidipine, at the same dose, completely
      suppressed it. Nifedipine had a potency between that of amlodipine and
      benidipine. Oral administration of lercanidipine showed similar effects to the
      intravenous administration test on ST change. High doses of amlodipine,
      benidipine and nifedipine suppressed ST-depression by almost 100%. In the
      methacholine-induced angina model, lercanidipine suppressed the ST elevation dose
      dependently. Amlodipine barely suppressed it, while benidipine at 30 microg/kg
      effected almost total suppression. Nifedipine had a potency between that of
      amlodipine and benidipine. Intraduodenal administration of lercanidipine also
      suppressed the ST-elevation dose dependently. Nifedipine, benidipine and
      amlodipine at 10 mg/kg all markedly suppressed the elevation. Lercanidipine was
      more potent than the other calcium channel antagonists tested. In conclusion, it
      was explicitly demonstrated that lercanidipine exerts potent protective effects
      on the ischemic electrocardiography (ECG) changes in a variety of putative angina
      pectoris models in rats. An antispasmolytic coronary vasodilating action may be
      involved in the mechanism. It is expected that lercanidipine will be useful as an
      antianginal agent.

PMID- 15863885
TI  - Inhibitory effects of triterpenes isolated from Chuling (Polyporus umbellatus
      Fries) on free radical-induced lysis of red blood cells.
AB  - Chuling, sclerotia of Polyporus umbellatus FRIES, has long been used for
      urological disorders in traditional medicine. In this study, we demonstrated that
      Chuling in vitro protects red blood cells from 2,2-azo-bis(2
      amidinopropane)dihydrochloride (AAPH)-induced hemolysis. The inhibitory effect
      was dose-dependent at concentrations of 50 to 1000 microg/ml. Moreover, tests
      were carried out to identify the main ingredient of Chuling with scavenging
      effect on free radicals. Triterpene carboxylic acids isolated from the methanol
      extract of Chuling, namely, polyporusterone A and polyporusterone B, were found
      to have inhibitory activities against AAPH-induced lysis of red blood cells. The
      anti-hemolytic effect was significantly stronger in polyporusterone B compared
      with polyporusterone A. Furthermore, the ingestion of 150 mg of Chuling was
      associated with a significant increase in free-radical scavenging effect of
      plasma in rats.

PMID- 15863886
TI  - In vitro cytotoxicity of Stealth liposomes co-encapsulating doxorubicin and
      verapamil on doxorubicin-resistant tumor cells.
AB  - Multidrug resistance (MDR) is a major obstacle to successful clinical cancer
      chemotherapy. A novel doxorubicin anti-resistant Stealth liposomes (DARSLs),
      prepared by co-encapsulating doxorubicin (DOX) and verapamil (VER) into stealth
      liposomes, has been developed. The average particle size of DARSLs was 118.1+/
      22.3 nm. Encapsulation efficiencies of DOX and VER in DARSLs were greater than
      95% and 70%, respectively. The IC(50) of DARSLs as measured by 3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay in multidrug resistant
      rat prostate cancer Mat-LyLu-B2 (MLLB2) cells was 0.079+/-0.017 microM, 13 fold
      less than that for liposomal DOX with free VER (LDFV 0.96+/-0.46 microM) but only
      about 2 times less than FDFV. The IC(50) cytotoxicity on MLLB2 cells of the
      various formulations was as follows: DARSLs approximately
      LDLV<FDFV<FDLV<LDFV<LD<FD, (LD: liposomal DOX; LV: liposomal VER; FD: free DOX;
      FV: free VER). Similar cytotoxicities were shown between DARSLs and FDFV in DOX
      resistant human uterus sarcoma MES-SA/DX5 cells, reversing DOX-resistance to that
      shown by FD on DOX-sensitive MES-SA cells. For MLLB2 cells, DARSLs was the most
      cytotoxic, but its intracellular concentration of DOX, measured as mean cellular
      fluorescence with flow cytometry was lower (p<0.01) than that observed with the
      FDFV formulation. In conclusion, DARSLs was an effective DOX formulation which
      could overcome drug resistance in DOX-resistant tumor cells, but its mechanisms
      of action may be complex.

PMID- 15863887
TI  - Immunomodulatory effects of gyokuheifusan on INF-gamma/IL-4 (Th1/Th2) balance in
      ovalbumin (OVA)-induced asthma model mice.
AB  - Asthma, a common, chronic lung disease in industrialized countries, is
      characterized by the production of large quantities of IgE antibody by B cells
      and a decrease of the IFN-gamma/IL-4 (Th1/Th2) ratio. Gyokuheifusan (GHS) is a
      classical formulation of traditional Chinese medicine (TCM) that is usually
      prescribed to prevent or treat respiratory tract diseases, such as respiratory
      infection and bronchial asthma. In order to evaluate the possible effectiveness
      of GHS on bronchial asthma, its immunomodulatory activity was examined in
      ovalbumin (OVA)-induced asthma model mice. All mice, except those in the normal
      group, were sensitized by intraperitoneal (IP) administration of OVA emulsified
      with Al(OH)(3), and a second immunization was given 6 d later. After a further
      13, 17 and 21d, mice were challenged with inhalation of aerosolized OVA solution,
      except for the normal group, which received mock sensitization using saline
      Al(OH)(3) emulsion and were challenged with an aerosol of saline without OVA.
      Allergen-specific IgE and total IgE in plasma were both significantly increased
      in the disease-control group. These increases were markedly blocked by GHS
      treatment. IFN-gamma released by splenocytes was significantly increased after co
      culture with OVA for 24 h, 48 h, and 72 h. GHS treatment further elevated the IFN
      gamma content compared with the disease-control group. The production of IL-4 was
      significantly increased when splenocytes were simulated with OVA for 72 h, but
      this increase was blocked by GHS treatment, so that GHS returned the decreased
      IFN-gamma/IL-4 (Th1/Th2) ratio of the disease-control group to the normal range.
      These results indicate that GHS may inhibit the development and severity of
      asthma.

PMID- 15863888
TI  - Lithium induced toxicity in rats: a hematological, biochemical and
      histopathological study.
AB  - Lithium (Li(+)) salts are commonly used in treating bipolar diseases. As
      physicians frequently keep the patients on long-term lithium therapy, awareness
      of the numerous side effects and pathogenesis of this lightest alkali metal is
      needed for such treatments. The current study was designed to evaluate the toxic
      effect of small doses of lithium nitrate in rats. In the present study we showed
      that the oral gavage feeding of lithium nitrate (20 mg Li/kg body wt) for 7 weeks
      on every alternate day to male albino wistar rats elicited a significant
      alterations in gross hematological values owing to hypochromic anemia and
      leucocytosis. Erythrocyte sedimentation rate (ESR) and clotting time depicted
      higher values and animals exhibited icteric condition. Serum levels of hexose,
      cholesterol and blood urea elevated; however, proteins depleted markedly. A
      significant increase in serum calcium and phosphorus has also been registered in
      lithium salt treated animals. The enzyme activities of alkaline phosphatase
      (Alpase) and acid phosphatase (Acpase) diminished depicting the disturbed general
      physiological status while there was a marked rise in the activities of
      transaminases (GOT and GPT) reflecting a stimulating transamination reaction in
      hepatic and renal tissues. The histopathological picture of the kidney tissues
      revealed many deformative alterations. Necrosis, binucleated cells and Kuffer's
      cells are visible in renal tissue. The epithelium lining of renal tissue was
      damaged and there were also some marked changes in glomerular region apart from
      intracellular alterations in corticomedulary region. The results of present study
      suggest that small doses of lithium induce toxicity in rats.

PMID- 15863889
TI  - Inhibition of tyrosinase activity by N,N-unsubstituted selenourea derivatives.
AB  - This study investigated inhibitory effects of N,N-unsubstituted selenourea
      derivatives on tyrosinase activity. Three types of N,N-unsubstituted selenoureas
      derivatives exhibited inhibitory effect on dopa (3,4-dihydroxyphenylalanine)
      oxidase activity of mushroom tyrosinase. Compound D at a concentration of 200
      microM exhibited 55.5% of inhibition on dopa oxidase activity of mushroom
      tyrosinase. This inhibitory effect was higher than that of kojic acid (39.4%), a
      well known tyrosinase inhibitor. Moreover, the compound D identified as a
      noncompetitive inhibitor by Lineweaver-Burk plot analysis. In addition, compound
      D also inhibited the melanin production in melan-a cells.

PMID- 15863890
TI  - In vitro study of the adsorption characteristics of drugs.
AB  - The adsorption characteristics of eight adsorbents, cholestyramine, colestimide,
      aluminum silicate, sucralfate, aluminum hydroxide, calcium polystyrene sulfonate,
      carbon sphere and medicinal carbon, on the drugs such as methotrexate,
      antidepressants, mizoribine and ciprofloxacin hydrochloride were investigated in
      vitro. Medicinal carbon showed an excellent adsorption of all the tested drugs
      while the carbon spheres showed a high but slow adsorption characteristic.
      Cholestyramine and colestimide showed a higher adsorption in methotrexate than
      the other adsorbents. Aluminum silicate and calcium polystyrene sulfonate showed
      higher adsorption in four antidepressants, clomipramine hydrochloride, imipramine
      hydrochloride, mianserin hydrochloride and trazodone hydrochloride. In
      mizoribine, there were no adsorbents that showed higher adsorption except for the
      medicinal carbon. In ciprofloxacin hydrochloride, aluminum preparations and
      calcium polystyrene sulfonate showed higher adsorption characteristics. It is
      suggested that several adsorbents are potentially useful treatments for drug
      overdoses, but that these adsorbents have the possibility of decreasing the
      effects of the co-administered medicines.

PMID- 15863891
TI  - Implication of the descending dynorphinergic neuron projecting to the spinal cord
      in the (+)-matrine- and (+)-allomatrine-induced antinociceptive effects.
AB  - We previously reported that either (+)-matrine (matridin-15-one) or (+)
      allomatrine (the C-6 epimer of matrine)-induced antinociceptive effect was
      attenuated by s.c. pretreatment with a kappa-opioid receptor (KOR) antagonist nor
      binaltorphimine (nor-BNI), indicating the critical role of KORs in
      antinociceptive effects induced by these alkaloids. In the present study, we
      found that i.c.v. administration of either (+)-matrine- or (+)-allomatrine
      induced antinociceptive effects in the mouse tail-flick and warm-plate test,
      whereas these alkaloids when given spinally failed to induce antinociception. In
      the guanosine-5'-O-(3-[(35)S]thio)trisphosphate ([(35)S]GTPgammaS) binding assay,
      we demonstrated that neither (+)-matrine nor (+)-allomatrine produced the
      stimulation of [(35)S]GTPgammaS binding in the membranes of the spinal cord,
      indicating that (+)-matrine- and (+)-allomatrine-induced supraspinal
      antinociceptive actions was not due to a direct stimulation of KORs by these
      alkaloids. Therefore, we next investigated the involvement of dynorphin A (1-17)
      release at the spinal or supraspinal site in (+)-matrine- or (+)-allomatrine
      induced antinociception. The i.c.v. pretreatment with an antiserum against
      dynorphin A (1-17) could not affect the antinociceptive effect induced by s.c.
      treatment of (+)-matrine. In contrast, the s.c.-administered (+)-matrine- and (+)
      allomatrine-induced antinociceptive effect was significantly attenuated by i.t.
      pretreatment of an antiserum against dynorphin A (1-17). The present data suggest
      that either (+)-matrine or (+)-allomatrine when given i.c.v. may stimulate the
      descending dynorphinergic neuron, resulting in the stimulation of KORs in the
      spinal cord, and this phenomenon in turn produces the antinociception in mice.

PMID- 15863892
TI  - Inhibitory effects of cancer cell proliferation by novel histone deacetylase
      inhibitors involve p21/WAF1 induction and G2/M arrest.
AB  - Two compounds were synthesized which have a structural component other than those
      of our new series histone deacetylase (HDAC) inhibitors to determine the
      structure-activity relationship. It was also examined whether the inhibitory
      effects on cancer cell proliferation by HDAC inhibitors involve p21/WAF1
      induction and G(1) or G(2)/M arrest in p53-mutated MG63 human osteosarcoma cells
      as do other HDAC inhibitors. It was demonstrated that inhibitors with the 2
      naphthylcarbonyl group and hydroxamic acid at both termimal sides as well as the
      phenylene component at the center of molecule markedly induce the p21/WAF1
      protein by stimulating p21/WAF1 gene promoter activity. Furthermore, cell cycle
      analysis revealed that these compounds arrest MG63 cells in the G(2)/M phase.

PMID- 15863893
TI  - Beta-D-xylopyranosyl-(1-->3)-beta-D-glucuronopyranosyl echinocystic acid isolated
      from the roots of Codonopsis lanceolata induces caspase-dependent apoptosis in
      human acute promyelocytic leukemia HL-60 cells.
AB  - We previously demonstrated that beta-D-xylopyranosyl-(1-->3)-beta-D
      glucuronopyranosyl echinocystic acid (codonoposide 1c), a biologically active
      compound isolated from the roots of Codonopsis lanceolata, is cytotoxic to cancer
      cells. In the present study, we investigated the effects of codonoposide 1c on
      the induction of apoptosis, and its putative action pathway in HL-60 human
      promyelocytic leukemia cells. Codonoposide 1c-treated HL-60 cells displayed
      several features of apoptosis, including DNA fragmentation, formation of DNA
      ladders by agarose gel electrophoresis, and externalization of annexin-V targeted
      phosphatidylserine (PS) residues. We observed that codonoposide 1c caused
      activation of caspase-8, caspase-9, and caspase-3. A broad caspase inhibitor (z
      VAD-fmk), caspase-8 inhibitor (z-IETD-fmk), and caspase-3 inhibitor (z-DEVD-fmk)
      almost completely suppressed codonoposide 1c-induced DNA fragmentation. We
      further found that codonoposide 1c induces mitochondrial translocation of Bid
      from cytosol, reduction of cytosolic Bax, and cytochrome c release from
      mitochondria. Interestingly, codonoposide 1c also triggered the mitochondrial
      release of Smac/DIABLO (second mitochondria-derived activator of caspases/direct
      inhibitor of apoptosis-binding protein with a low isoelectric point) into
      cytosol, and a reduction in X-linked inhibitor of apoptosis protein (XIAP). Taken
      together, our data indicate that codonoposide 1c is a potent inducer of apoptosis
      and facilates its activity via Bid cleavage and translocation to mitochondria,
      Bax reduction in cytosol, release of cytochrome c and Smac/DIABLO into the
      cytosol, and subsequently caspase activation, providing a potential mechanism for
      the cytotoxic activity of codonoposide 1c.

PMID- 15863894
TI  - Vascular relaxation by the methanol extract of Sorbus cortex via NO-cGMP pathway.
AB  - The methanol extract of Sorbus commixta cortex (MSC) induced relaxation of the
      phenylephrine-precontracted aorta in a dose-dependent manner, which was
      disappeared by removal of functional endothelium. Pretreatment of the aortic
      tissues with N(G)-nitro-L-arginine methyl ester (L-NAME), methylene blue, or 1H
      [1,2,4]-oxadiazole-[4,3-alpha]-quinoxalin-1-one (ODQ) inhibited the vascular
      relaxation induced by MSC. MSC-induced vascular relaxations were also markedly
      attenuated by addition of verapamil or diltiazem, while the relaxant effect of
      MSC was not blocked by pretreatment with indomethacine, glibenclamide,
      tetraethylammonium (TEA), atropine, or propranolol, respectively. Incubation of
      endothelium-intact carotid arteries or of human umbilical vein endothelial cells
      (HUVECs) with MSC increased the production of guanosine 3',5'-cyclic
      monophosphate (cGMP). Moreover, MSC-induced cGMP production was effect was
      blocked by pretreatment with L-NAME or ODQ. These results suggest that MSC
      dilates vascular smooth muscle via endothelium-dependent nitric oxide-cGMP
      signaling pathway, possible involvement of L-type Ca(2+) channel.

PMID- 15863895
TI  - Effects of traditional Chinese medicine on bone loss in SAMP6: a murine model for
      senile osteoporosis.
AB  - We evaluated the effects of the traditional Chinese medicines, Hachimi-jio-gan,
      Juzen-taiho-to and Unkei-to, on bone loss in murine model of senile osteoporosis
      (SAMP6). Two-month-old SAMP6 were divided into control and experimental groups.
      The control mice had the tap water available as the only drinking fluid. The
      experimental mice were given 0.05% aqueous solution of Hachimi-jio-gan, Juzen
      taiho-to or Unkei-to for three months. The solution intake of a mouse averaged 5
      ml per day. The bones were studied morphologically and histomorphometrically,
      together with bone mineral density (BMD), serum parathyroid hormone (PTH) and
      estradiol levels. In the control group, BMD and the amount of bone forming
      surface were low, the serum PTH level was high when compared with the normal mice
      SAMR1. Many osteocytes and osteoblasts showed degenerative changes and numerous
      mast cells were observed in the bone marrow. Compared with controls, the serum
      estradiol level was higher in the Unkei-to group. However, we did not find any
      significant changes of bones. In the Hachimi-jio-gan and Juzen-taiho-to groups,
      the bone mass and the amount of bone forming surface increased. Most of the
      osteocytes and osteoblasts appeared normal. As compared with controls, the number
      of mast cells in bone marrow decreased in the Hachimi-jio-gan group. The serum
      PTH level had declined in the Juzen-taiho-to group. The present study provides
      certain evidence that Hachimi-jio-gan and Juzen-taiho-to are effective in
      preventing bone loss in SAMP6, while Unkei-to can only improve the ovary
      function.

PMID- 15863896
TI  - Transdermal absorption of propofol in rats.
AB  - Propofol (PF), a highly lipophilic anesthetic, has several desirable properties,
      such as the rapid onset and cessation of its effects upon intravenous infusion.
      In this study, the transdermal absorption of PF was investigated with the aim of
      the development of an alternative route of administration. PF solutions
      containing isopropyl myristate (IPM), ethanol or propylene glycol (PG) at various
      concentrations were prepared and applied to the abdominal skin of rats.
      Petrolatum and fatty alcohol propylene glycol (FAPG) ointments containing PF were
      also prepared and applied to the dorsal skin. Eyelid opening was measured and the
      ratio of the measured value to the initial value was calculated to evaluate the
      level of the pharmacological effect of the preparation. The PG solution
      containing 80% PF achieved higher plasma PF concentrations than the 100% PF
      solution. The PF-FAPG ointment produced a higher plasma PF concentration than the
      PF-petrolatum ointment. Furthermore, a drowsy state was confirmed after
      transdermal administration of 42% PF-FAPG ointment. These results indicate that
      the combination of PF and PG was appropriate for the transdermal absorption of
      PF, and PF was absorbed through the rat skin to an extent sufficient to cause a
      continuous sedative effect.

PMID- 15863897
TI  - Pharmacokinetic variability of routinely administered bisoprolol in middle-aged
      and elderly Japanese patients.
AB  - The nonlinear mixed effects model (NONMEM) was used to analyze the
      pharmacokinetics of routinely administered bisoprolol in middle-aged and elderly
      Japanese patients. The subjects consisted of 29 males and 11 females with a mean
      age of 63.5+/-10.1. Data on the plasma concentration of bisoprolol from 94 blood
      samples obtained at steady-state following repetitive oral administration were
      analyzed using the NONMEM program, where a one-compartment model with repetitive
      bolus dosing was parameterized in terms of oral clearance (CL/F) and apparent
      volume of distribution (V/F). Individual CL/F values were correlated with body
      weight (WT) and creatinine clearance (CLcr). The relation between CLcr and the
      CL/F of bisoprolol was not altered by the CYP2D6 and CYP2C19 genotypes, gender,
      or age. The mean CL/F value estimated with NONMEM was 0.0612.WT+1.15.CLcr (l/h),
      and the mean V/F value was 2.61.WT (l). The residual interindividual variability
      of CL/F and V/F were 22.0% and 12.6%, respectively. The pharmacokinetic
      variability of bisoprolol is small even in routinely treated Japanese patients,
      provided that both body weight and renal function are taken into account for the
      prediction of oral clearance of the drug.

PMID- 15863898
TI  - Inhibitory effects of nicardipine to cytochrome P450 (CYP) in human liver
      microsomes.
AB  - To anticipate drug-drug interactions by nicardipine in vivo, cytochrome P450
      (CYP) forms responsible for the metabolism of nicardipine and inhibition of CYP
      dependent drug metabolism by nicardipine were investigated. Microsomes of human B
      lymphoblastoid cells expressing each human CYP form were used for the metabolism
      of nicardipine. Inhibitory effects of nicardipine on drug metabolism were studied
      using human liver microsomes. CYP2C8, CYP2D6 and CYP3A4 were identified as major
      CYP forms for the metabolism of nicardipine in human liver microsomes.
      Nicardipine strongly inhibited two-pathways of triazolam hydroxylation both
      catalyzed by CYP3A4. Comparison of three Ca(2+) antagonists, nicardipine,
      nifedipine, and diltiazem revealed that only nicardipine showed such a strong
      inhibitory potency on the typical CYP2D6-catalyzed drug metabolism. Furthermore,
      nicardipine inhibited other reactions catalyzed by CYP1A, CYP2A6, CYP2C8, CYP2C9
      and CYP2C19 with K(i) values ranging from 1.1 to 29.4 microM. In conclusion,
      nicardipine was a relatively potent inhibitor of human CYP2D6, CYP3A4 and CYP2C
      (especially for CYP2C8 and CYP2C19) in vitro, suggesting that drug-drug
      interactions between nicardipine and other drugs metabolized mainly by these CYP
      forms appear to occur in vivo.

PMID- 15863899
TI  - Tissue-specific mRNA expression profiles of human toll-like receptors and related
      genes.
AB  - The mRNA expression levels of 10 toll-like receptors (TLRs) and 21 related genes
      in total RNA from pooled specimens of fetal human tissues (brain and liver), from
      single and pooled specimens of various adult human tissues (adrenal gland, brain,
      heart, kidney, liver, lung, placenta, prostate, salivary gland, skeletal muscle,
      small intestine, spinal cord, spleen, testis, thymus, thyroid gland, trachea, and
      uterus), and from two cell lines (Hep G2 and HeLa) were analyzed by real-time
      reverse transcription PCR. The mRNA expression of the 10 human TLRs was
      successfully detected in all of the tissues and in HeLa cells. TLR2, TLR3, TLR6,
      and TLR9 were consistently expressed in Hep G2 cells, but TLR1, TLR4, TLR5, TLR7,
      TLR8, and TLR10 showed no or very weak expression in these cells. The mRNA
      expression of many TLR-related genes (ICAM1, CD14, MyD88, LY96, TRIF, TICAM2,
      TIRAP, CD83, SOCS1, TNFAIP3, TOLLIP, IRAK1, IRAK2, IRAK4, and TRAF6) was
      successfully detected in all of the tissues and cell lines. The mRNA expression
      of CD80, CD86, IRAK3, and CCL2 was successfully detected in all of the tissues
      and cell lines except for Hep G2 cells. The mRNA expression of CCL5 was
      successfully detected in all of the tissues and cell lines except for fetal
      brain. The mRNA expression of CXCL10 was successfully detected in all of the
      tissues except for fetal and adult brain. These results provide valuable
      information for studies concerning the regulation of TLR-related genes.

PMID- 15863900
TI  - Inhibition of human immunodeficiency virus type-1 (HIV-1) replication at a
      reverse transcription step by human cell factor(s).
AB  - Infection of human cell with human immunodeficiency virus type-1 (HIV-1) was
      suppressed by cellular genetic factor(s) at reverse transcription step. Although
      same amount of virus adsorbed on both cells, small amount of HIV-1 (IIIB strain)
      infected HeLa (MAGI/CCR5) cell, while large amount of HIV-1 infected HOS
      (GHOST/CXCR4) cell. Regulation of virus replication at postentry level by
      cellular factor(s) had an important role for low efficiency of HIV-1 infection to
      MAGI/CCR5 cell. Provirus DNA formation in MAGI/CCR5 cell was less efficient than
      in GHOST/CXCR4 cell. Once GHOST/CXCR4 cell was fused with MAGI/CCR5 cell,
      susceptibility against HIV-1 decreased. Further, HIV-1 reverse transcriptase (RT)
      activity was strongly inhibited by cytosolic protein, derived from MAGI/CCR5
      cell, in vitro. This research cleared a certain human cell genetically carries
      some factor(s) which inhibits the activity of HIV-1 RT.

PMID- 15863901
TI  - Structure and characterization of AAT-1 isoforms.
AB  - A novel protein, AAT-1, was identified as a AMY-1-binding protein and three
      splicing variants of AAT-1, AAT-1alpha, -beta and -gamma were identified. The
      function of AAT-1 is thought to be related to spermatogenesis. In this study, we
      further identified other splicing isoforms of AAT-1, AAT-1L, AAT-1M and AAT-1S,
      consisting of 767, 603 and 252 amino acids, respectively. These isoforms were
      found to use a promoter different from that used by AAT-1alpha, -beta and -gamma
      in the aat-1 gene, which contains 20 exons. Only 60 amino acids in the C-terminal
      portion of AAT-1 derived from exons 15-17 are common among AAT-1L, AAT-1M, AAT-1S
      and AAT-1alpha. While AAT-1alpha is specifically expressed in the testis, AAT-1L,
      AAT-1M, AAT-1S were found to be differentially expressed in human tissues. All of
      the isoforms of AAT-1 were found to bind to and colocalized with AMY-1 in human
      cells. While AAT-1L and AAT-1M were found to be localized diffusely in the
      cytoplasm, AAT-1S, like AAT-1alpha, was found to be localized in the mitochondria
      like structure, suggesting different roles of AAT-1 isoforms in cells.

PMID- 15863902
TI  - Antispasmodic activity of fractions and cynaropicrin from Cynara scolymus on
      guinea-pig ileum.
AB  - This study describes the antispasmodic activity of some fractions and
      cynaropicrin, a sesquiterpene lactone from Cynara scolymus, cultivated in Brazil,
      against guinea-pig ileum contracted by acetylcholine. The dichloromethane
      fraction showed the most promising biological effects, with an IC(50) of 0.93
      (0.49-1.77) mg/ml. Its main active component, the sesquiterpene lactone
      cynaropicrin, exhibited potent activity, with IC(50) of 0.065 (0.049-0.086)
      mg/ml, being about 14-fold more active than dichloromethane fraction and having
      similar potency to that of papaverine, a well-known antispasmodic agent. The
      results confirm the popular use of artichoke for the treatment of
      gastrointestinal disturbances, and encourage new studies on this compound, in
      order to obtain new antispasmodic agents.

PMID- 15863903
TI  - Suppression of proliferation of poliovirus and porcine parvovirus by novel
      phenoxazines, 2-amino-4,4 alpha-dihydro-4 alpha-7-dimethyl-3H-phenoxazine-3-one
      and 3-amino-1,4 alpha-dihydro-4 alpha-8-dimethyl-2H-phenoxazine-2-one.
AB  - The present study aimed at investigating the antiviral effects of 2-amino
      4,4alpha-dihydro-4alpha-7-dimethyl-3H-phenoxazine-3-one (Phx-1) and 3-amino
      1,4alpha-dihydro-4alpha-8-dimethyl-2H-phenoxazine-2-one (Phx-2) on 6
      representative viruses: poliovirus, porcine parvovirus, simian virus 40 (SV-40),
      herpes simplex virus-1 (HSV-1), Sindbis virus, and vesicular stomatitis virus
      (VSV). Phx-1 and Phx-2 suppressed the proliferation of poliovirus in Vero cells
      and that of porcine parvovirus in ESK cells at concentrations between 0.25
      microg/ml and 2 microg/ml, when the cells were treated with Phx-1 and Phx-2 for 1
      h and then inoculated with these viruses. The proliferation of the other viruses,
      SV-40, HSV-1, Sindbis virus, and VSV, in the host cells was not influenced by Phx
      1 or Phx-2 at concentrations less than 20 microg/ml. The results suggest that Phx
      1 and Phx-2 may be useful to prevent the proliferation of poliovirus and porcine
      parvovirus infection and may contribute to developing new antiviral drugs in
      future.

PMID- 15863904
TI  - Anti-inflammatory benzene diamine compound inhibited toll-like receptor 4
      mediated inducible nitric oxide synthase expression and nuclear factor-kappa B
      activation.
AB  - Toll-like receptor 4 (TLR4) is known to play an important role in innate immune
      responses. In the present study, chemically synthetic compound of N(1)-benzyl-4
      methylbenzene-1,2-diamine (BMD) was discovered to inhibit nitric oxide (NO)
      production in macrophages RAW 264.7 stimulated with lipopolysaccharide (LPS) or
      fibronectin as TLR4 activators. The BMD compound attenuated LPS-induced synthesis
      of both mRNA and protein of NO synthase (iNOS), and inhibited LPS or fibronectin
      mediated iNOS promoter activity, indicating that the compound down-regulated iNOS
      expression at transcription level. As a mode of the anti-inflammatory action
      shown by BMD compound, inhibitory effect on nuclear factor (NF)-kappaB activation
      was also investigated in macrophages RAW 264.7 stimulated with the TLR4
      activators.

PMID- 15863905
TI  - Inhibitory effects of the flavonoids isolated from Waltheria indica on the
      production of NO, TNF-alpha and IL-12 in activated macrophages.
AB  - Three flavonoids were isolated from the whole plants of Waltheria indica and
      biological properties investigated. On the basis of their spectroscopic data,
      these compounds were identified as (-)-epicatechin, quercetin, and tiliroside.
      These flavonoids significantly and dose-dependently inhibited the production of
      the inflammatory mediator nitric oxide (NO), and the cytokines (tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-12), in lipopolysaccharide (LPS) and
      interferon (IFN)-gamma activated murine peritoneal macrophages, without
      displaying cytotoxicity. The order of inhibitory activity was
      quercetin>tiliroside>(-)-epicatechin. Furthermore, peritoneal macrophages were
      pre-activated with LPS/IFN-gamma for 24 h, and the inhibitory effects of the
      above mentioned isolates on the production of NO were determined after a further
      24 h, to address the possible mechanisms of their action. The present study
      supports the use of W. indica for the treatment of inflammatory diseases in
      traditional medicine.

PMID- 15863906
TI  - Inhibitory effects of isorhamnetin-3-O-beta-D-glucoside from Salicornia herbacea
      on rat lens aldose reductase and sorbitol accumulation in streptozotocin-induced
      diabetic rat tissues.
AB  - The inhibitory effects of compounds from Salicornia herbacea (Chenopodiaceae) on
      rat lens aldose reductase (RLAR) and sorbitol accumulation in streptozotocin
      induced diabetic rat tissues were investigated. The various fractions from the
      MeOH extract of S. herbacea were tested for their effects on RLAR in vitro. Among
      them, the EtOAc fraction was found to exhibit a potent RLAR inhibition
      (IC(50)=0.75 microg/ml), from which an active principle as a potent AR inhibitor
      was isolated and its chemical structure was elucidated as isorhamnetin-3-O-beta-D
      glucoside (1) by spectral analysis. Compound 1 exhibited a potent RLAR inhibition
      in vitro, its IC(50) being 1.4 microM. Compound 1, when administered orally at 25
      mg/kg in streptozotocin (STZ)-induced diabetic rats, caused not only a
      significant inhibition of serum glucose concentration but also sorbitol
      accumulation in the lenses, red blood cells (RBC), and sciatic nerves. These
      results indicate that compound 1 from S. herbacea is a leading compound for
      further study as a new drug for the prevention and/or treatment of diabetes and
      its complications.

PMID- 15863907
TI  - The favorable effect of style of Zea mays L. on streptozotocin induced diabetic
      nephropathy.
AB  - The effectivity of water extract from the style of Zea mays on diabetic
      nephropathy was investigated in the development of new natural medicinal
      resources. Streptozotocin (STZ) induced diabetic rats were used to evaluate the
      therapeutic effect of the style. Urinary albumin excretion and creatinine
      clearance were examined for diagnosis of diabetic nephropathy. From these results
      it was learned that the style of Z. mays prevented glomerular hyperfiltration.
      The present findings indicated that the water extract of the title material
      suppressed the progression of diabetic glomerular sclerosis in STZ-induced
      diabetic rat.

PMID- 15863908
TI  - AIP1, a water-soluble fraction from Artemisia iwayomogi, suppresses thymocyte
      apoptosis in vitro and down-regulates the expression of Fas gene.
AB  - The AIP1 fraction, a small water-soluble fraction purified from Artemisia
      iwayomogi, was shown to increase antibody production and suppress transplanted
      tumor cell growth in mice. In order to understand its immuno-modulating activity,
      we have examined the effect of the AIP1 on mouse thymocytes in vitro. Treatment
      of mouse thymocytes in culture with the fraction resulted in the suppression of
      the cell death and the extension of the cell survival. A mouse gene array
      provided a profile of gene expression change showing the pattern of up- and down
      regulated genes by the AIP1 treatment, suggesting that the Fas/FasL-dependent
      apoptosis pathway might be modulated by the fraction.

PMID- 15863909
TI  - Isoflavonoid from Viola hondoensis, regulates the expression of matrix
      metalloproteinase-1 in human skin fibroblasts.
AB  - Long term and repeated exposure of ultraviolet (UV) light, a harmful
      environmental stress, on the skin often induces chronic skin diseases such as
      skin cancer as well as photoaging (premature skin aging), and the mechanisms of
      these skin damages are closely associated with up-regulation of matrix
      metalloproteinases (MMPs) activities. Here we investigated the effect of 2',4',7
      trihydroxyisoflavone isolated from the whole plants of Viola hondoensis
      (Violaceae) on the expression of MMPs in UV-irradiated human skin fibroblasts in
      vitro. 2',4',7-Trihydroxyisoflavone markedly reduced UV-induced MMP-1 expression,
      but not MMP-2, at the both mRNA and protein levels in a dose-dependent manner.
      Our report is the first description for the ability of 2',4',7
      trihydroxyisoflavone to regulate MMP-1 expression specifically.

PMID- 15863910
TI  - Studies on palauan medicinal herbs. II. Activation of mouse macrophages RAW 264.7
      by Ongael, leaves of Phaleria cumingii (Meisn.) F. Vill. and its
      acylglucosylsterols.
AB  - The extract of Ongael [leaves of Phaleria cumingii (MEISN.) F. VILL.], a Palauan
      medicinal herb, enhanced an in vitro phagocytic activity of mouse macrophages RAW
      264.7 cells (RAW 264.7). Activity-guided fractionation of the Ongael extract by
      the in vitro phagocytosis assay using RAW 264.7 led to the isolation of a mixture
      of acylglucosylsterols (1) as an active constituent along with other inactive
      constituents, tetracosanol and mangiferin. On the basis of chemical modifications
      and spectral analyses, the compound 1 was deduced to be a mixture of the known 3
      O-(6-O-acyl-beta-D-glucosyl)-beta-sitosterols, the acyl moiety being mainly
      palmitoyl (57%), oleoyl (12%) and alpha-linolenoyl (12%) with small amount of
      stearoyl (7%) and linoleoyl (4%).

PMID- 15863911
TI  - Extract of Ginkgo biloba leaves attenuates kainate-induced increase in
      intracellular Ca2+ concentration of rat cerebellar granule neurons.
AB  - In order to reveal one of possible mechanisms for neuronal protective action of
      extract of Ginkgo biloba leaves (EGBL), the effect of EGBL on kainate- and KCl
      induced increases in intracellular Ca(2+) concentration ([Ca(2+)]i) of rat
      cerebellar neurons was examined using a confocal laser microscope with
      appropriate fluorescent probes. EGBL at 3 microg/ml started to attenuate kainate
      induced increase of [Ca(2+)]i and further increase in EGBL concentration (up to
      30 microg/ml) concentration-dependently and significantly inhibited the kainate
      response. The complete inhibition by EGBL was observed in some neurons when the
      concentration was 10-30 microg/ml. The kainate-induced increase in [Ca(2+)]i was
      mainly due to Ca(2+) influx through voltage-dependent Ca(2+) channel opened by
      membrane depolarization via activation of kainate receptor-channel. However, the
      increase in [Ca(2+)]i by KCl was not significantly affected by EGBL at
      concentrations where the kainate response was greatly inhibited. EGBL consisting
      of flavone glycosides and terpene lactones is known to be an antioxidant.
      Furthermore, in this study, it is shown that EGBL exerts an inhibitory action on
      kainate receptor (a subtype of glutamate receptor). Since some of
      neurodegenerative diseases are due to cell death induced by glutamate
      excitotoxicity and oxidative stress, EGBL may be very suitable for preventing
      and/or treating such diseases.

PMID- 15863912
TI  - Hypoglycemic effects of turmeric (Curcuma longa L. rhizomes) on genetically
      diabetic KK-Ay mice.
AB  - The turmeric (Curcuma longa L. rhizomes) EtOH extract significantly suppressed an
      increase in blood glucose level in type 2 diabetic KK-A(y) mice. In an in vitro
      evaluation, the extract stimulated human adipocyte differentiation in a dose
      dependent manner and showed human peroxisome proliferator-activated receptor
      (PPAR)-gamma ligand-binding activity in a GAL4-PPAR-gamma chimera assay. The main
      constituents of the extract were identified as curcumin, demethoxycurcumin,
      bisdemethoxycurcumin, and ar-turmerone, which had also PPAR-gamma ligand-binding
      activity. These results indicate that turmeric is a promising ingredient of
      functional food for the prevention and/or amelioration of type 2 diabetes and
      that curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone mainly
      contribute to the effects via PPAR-gamma activation.

PMID- 15863913
TI  - Development of a novel synthetic method for ring construction using
      organometallic complexes and its application to the total syntheses of natural
      products.
AB  - Organometallic complexes are useful tools in synthetic organic chemistry. We
      investigated a novel synthetic method for ring construction using organometallic
      complexes and synthesized natural products and biologically active substances
      using these methods. Metalacycles formed from an early transition metal and
      diene, enyne, and diyne are stable under the reaction conditions and they are
      easily converted into compounds with functional groups by the addition of various
      agents. We have developed a novel synthetic method of heterocycles from enyne and
      diene using Cp2ZrBu2. The total syntheses of (-)-dendrobine, (+/-)-mecembrane,
      and (+/-)-mecembrine were achieved using this procedure. To synthesize these
      natural products as a chiral form, a novel palladium-catalyzed asymmetric allylic
      amination was developed, and chiral 2-arylcyclohexenylamine derivatives were
      synthesized. From these compounds, the total syntheses of (-)-mesembrane, (-)
      mesembrine, (+)-crinamine, (-)-haemanthidine, and (+)-pretazetine were achieved.
      By further development of this procedure, a chiral 2
      siloxymethylcyclohexenylamine derivative could be synthesized and the novel
      synthesis of indole derivatives was developed from this compound. From this
      indole derivative, (-)-tsubifoline and (-)-strychnine were synthesized.

PMID- 15863914
TI  - Formation constants of chromium(III), scandium(III) and yttrium(III) complexes of
      some hydroxy naphthoic acids.
AB  - The complexes of chromium(III), scandium(III) and yttrium(III) formed by 1
      hydroxy-2-naphthoic acid (1,2-HNA: H2L) and 3-hydroxy-2-naphthoic acid (3,2-HNA:
      H2L) were investigated by potentiometry and spectroscopy at 25+/-0.1 degrees C
      and at an ionic strength of 0.1 M KNO3 in 50% ethanol-water (v/v) medium. The
      stoichiometries of these three M(III) complexes formed with these hydroxy
      naphthoic acids and with hydroxo ion were defined and their formation constants
      were determined and compared. Thus, the removing capacities of these ligands
      could be examined by calculating the equilibrium concentration of Cr(III) that
      exists in the discharge water of various industries since Cr(III) ions are the
      main pollutants present during waste water treatment in our city, Bursa.

PMID- 15863915
TI  - A facile one-pot benzylation of sodium enolates using trifluoromethanesulfonic
      anhydride and diphenyl sulfoxide.
AB  - A facile one-pot C-benzylation of various sodium enolates derived from methyl
      malonate, beta-ketoesters, a beta-cyanoester, a beta-cyanosulfone, ketones and a
      carboxylic ester is reported. Reaction of alkoxydiphenylsulfonium salts formed by
      treating various benzyl alcohols with diphenyl sulfide
      bis(trifluoromethanesulfonate) (derived from trifluoromethanesulfonic anhydride
      and diphenyl sulfoxide) proceeded smoothly, and the corresponding C-benzylated
      products were afforded in good to high yields.

PMID- 15863916
TI  - Quality assessment of radix salviae miltiorrhizae.
AB  - This paper describes an improved quality assessment method for Radix Salviae
      Miltiorrhizae (Root of Salvia miltiorrhiza BGE.) which was established using
      chromatographic fingerprinting and quantification of multiple marker compounds in
      the crude drug. High-performance thin-layer chromatography (HPTLC) fingerprinting
      of water-soluble phenolics and nonpolar tanshinones was performed separately and
      the authentication of Radix Salviae Miltiorrhizae was achieved by comparing the
      fingerprints of the samples with those of the reference crude drug and by
      comparing the Rf values of the bands in TLC fingerprints with those of reference
      compounds. HPLC fingerprints were obtained by simultaneous separation of
      phenolics and diterpenoids in Radix Salviae Miltiorrhizae. The HPLC fingerprints
      of seven batches of samples from different regions of China showed similar
      chromatographic patterns, and seven peaks were selected as characteristic peaks.
      The relative retention time of these characteristic peaks in the HPLC
      fingerprints was established as an important parameter for the identification of
      this herbal medicine. The pharmacologically active marker compounds salvianolic
      acid B, rosmarinic acid, and tanshinone IIA in herbal medicine were
      quantitatively determined using reverse-phase HPLC techniques. The HPLC
      quantitation methods of the three marker compounds were validated and the
      measurement uncertainty, which is important for setting the proposed content
      limit of the marker compounds in herbal medicine, were further evaluated.

PMID- 15863917
TI  - Tabletting of solid dispersion particles consisting of indomethacin and porous
      silica particles.
AB  - We attempted to make the rapidly dissolving tablet (Tab) containing solid
      dispersion particles (SD) with indomethacin (IMC) and porous silica (Sylysia350)
      as carrier prepared by using spray-drying technique. Rapidly dissolving tablet
      was formulated with mannitol as a diluent and low substituted
      hydroxypropylcellulose (L-HPC) or partly pre-gelatinized starch (PCS) as a
      disintegrant. The percent dissolved from Tab (SD) was higher than that of tablet
      containing physical mixture (PM) at 20 min. Nearly 100% of drug in Tab (SD) was
      dissolved within 60 min, while the drug dissolution of Tab (PM) was not completed
      at the same time period. In addition, the tensile strength of Tab (SD) was much
      higher than that of Tab (PM). Adding L-HPC in Tab (SD) (Tab (SD-L-HPC)), the
      percent dissolved from Tab (SD-L-HPC) at 5 min became much higher than that from
      Tab (SD). The dissolution profile of IMC from Tab (SD-L-HPC) was almost the same
      irrespective of the compression pressure, while the tensile strength of tablet
      increased with increasing the compression pressure. In comparing the compaction
      property of these tablets by observing the ratio of residual die wall pressure
      (RDP) to maximum die wall pressure (MDP) (RDP/MDP), it was found that addition of
      L-HPC in the tablet formulation improved compactibility. In case that PCS was
      formulated as disintegrant, Tab (SD-PCS), similar improvement in the dissolution
      profile and tensile strength was observed, though the dissolution rate of IMC
      from Tab (SD-PCS) was slightly lower than that from Tab (SD-L-HPC) irrespective
      of the compression pressure.

PMID- 15863918
TI  - Conversion of sterically hindered diacylated 1,2-phenylenediamines into 2
      substituted benzimidazoles.
AB  - A series of bulky 2-substituted benzimidazoles was designed in order to find new
      leads for several biological targets. Formation by cyclodehydration from their
      monoacylated counterparts was shown to be strongly dependent upon the nature of
      the acyl group. In the case of a dicyclohexylmethyl group, cyclization was only
      observed in a p-toluenesulfonic acid/toluene mixture from the symmetrical
      diacylated precursor. Analysis of the mechanism was begun starting from mixed
      diacylated derivatives.

PMID- 15863919
TI  - Effect of structural relaxation on the physical and aerosol properties of
      amorphous form of FK888 (NK1 antagonist).
AB  - FK888 (NK1 antagonist) is a candidate drug for migraine and selected as a model
      of amorphous drug. FK888 was micronized to develop as dry powder inhalers (DPIs)
      taking into consideration of its water insoluble property. The glass transition
      temperature (Tg) and fragility (m) were 90 degrees C and 118, respectively, and
      it was categorized as a fragile glass based on Angell's concept. FK888 was
      structurally relaxed by aging below Tg, then the effect of aging on their
      physical and aerosol properties were investigated. The investigation on the
      moisture sorption-desorption isotherms of FK888 indicated that aged FK888
      adsorbed less amount of water than that of unaged FK888. This unique moisture
      sorption-desorption behavior of the aged sample is explained by structural
      relaxation accompanying decrease of free volume and/or increase of density. As
      for the dissolution rate of unaged and aged FK888, they showed the similar value,
      suggesting that there would be no difference in bioavailability. In relation to
      the stability, FK888 DPIs prepared by unaged and aged FK888 were stored at 70
      degrees C, and the respirable fraction of FK888 DPIs was evaluated by using
      multistage cascade impactor (USP apparatus 3). As a result, the respirable
      fraction of FK888 DPIs prepared by unaged sample was significantly decreased
      compared to the aged sample, suggesting that agglomeration may occur in the
      unaged sample during the storage. This phenomenon was supported by that the
      unaged sample showed a significant decrease in the surface area compared to that
      of the aged sample when stored at various conditions.

PMID- 15863920
TI  - Effect of compression on interaction between 1,4-dihydropyridine compounds and
      lactose monohydrate.
AB  - Manidipine dihydrochloride or benidipine hydrochloride will change to hydrate
      form in part, when differential scanning calorimetric (DSC) measurement is
      carried out together with lactose monohydrate. This interaction was accelerated
      by compressing their mixture. It can be suggested that the interaction may cause
      by the disruption of crystal structure of lactose monohydrate due to compression
      to set free of water molecules. A new DSC peak at 170 degrees C, which was not
      observed in each component, appeared in DSC measurement of a mixture. This will
      be based on hydrate formed by the interaction, i.e., movement of water molecules.
      The profile of the plotting of the DSC peak area ratio before and after
      compression against the compression force changed by the molar ratio of lactose
      monohydrate in a mixture. In the case of low molar ratio of lactose monohydrate,
      profiles for manidipine dihydrochloride and benidipine hydrochloride differed
      from each other. This will be because manidipine dihydrochloride is stickier than
      benidipine hydrochloride. The profile for manidipine dihydrochloride became more
      gradual and showed lag compression force region when the amount of addition of
      the lubricant, magnesium stearate in a mixture increased. The endothermic peak
      area at 170 degrees C for manidipine dihydrochloride was larger than that for
      benidipine hydrochloride. It should be suggested that benidipine hydrochloride is
      easier to be transformed to its hydrate than manidipine dihydrochloride.

PMID- 15863921
TI  - Quantitative analysis of the marker compounds in Salvia miltiorrihiza root and
      its phytomedicinal preparations.
AB  - A HPLC method is described in order to separate and identify 4 phenolic compounds
      including lithospermic acid B, 3,4-dihydroxyphenyllactic acid (danshensu),
      rosmarinic acid, and protocatechuic aldehyde as well as 3 lipophilic ones
      (tanshinone I, tanshinone II(A) and cryptotanshinone) from the roots of Salvia
      miltiorrihiza or the herbal product containing S. miltiorrihiza available in
      Chinese or Japanese market. The influence of extractive conditions, such as
      method, solvents and time, on the 4 phenolic marker components in S.
      miltiorrihiza is well discussed. In order to investigate the stability of
      lithospermic acid B, the preparation samples of an injection and a granule were
      analyzed after being stored at 4 degrees C, 20 degrees C and 40 degrees C for up
      to six months.

PMID- 15863922
TI  - Chemical constituents of Malagasy liverworts, part III: sesquiterpenoids from
      Bazzania decrescens and Bazzania madagassa.
AB  - In the continuation of our investigation of the phytochemical constituents of
      Malagasy liverworts, a new cuparane-type sesquiterpenoid together with five known
      compounds was isolated from Bazzania decresens. Bazzania madagassa furnished a
      new cyclomyltaylane-type sesquiterpenoid and a new acoradienol. The structures of
      the isolated compounds were determined based on a combination of physical and
      spectroscopic evidence. The chemosystematics of the genus Bazzania as well as the
      biogenesis of cyclomyltaylane sesquiterpenoids in liverworts is discussed.

PMID- 15863923
TI  - Calculation of the viscosity of binary liquids at various temperatures using
      Jouyban-Acree model.
AB  - Applicability of the Jouyban-Acree model for calculating absolute viscosity of
      binary liquid mixtures with respect to temperature and mixture composition is
      proposed. The correlation ability of the model is evaluated by employing
      viscosity data of 143 various aqueous and non-aqueous liquid mixtures at various
      temperatures collected from the literature. The results show that the model is
      able to correlate the data with an overall percentage deviation (PD) of 1.9+/
      2.5%. In order to test the prediction capability of the model, three experimental
      viscosities from the highest and lowest temperatures along with the viscosities
      of neat liquids at all temperatures have been employed to train the model, then
      the viscosity values at other mixture compositions and temperatures were
      predicted and the overall PD obtained is 2.6+/-4.0%.

PMID- 15863924
TI  - Synthesis and optical resolution of 2-aryl-2-fluoropropionic acids, fluorinated
      analogues of non-steroidal anti-inflammatory drugs (NSAIDs).
AB  - We report the synthesis of optically active 2-aryl-2-fluoropropionic acids 2 as
      non-epimerizable mimics of 2-arylpropionic acids 1, a class of compounds which
      have been widely used as non-steroidal anti-inflammatory drugs (NSAIDs). This is
      a continuation of our research involving the design, synthesis, and evaluation of
      chiral fluorine-containing organic molecules as effective analogues of
      pharmacologically important compounds.

PMID- 15863925
TI  - Application of intramolecular 1,3-dipolar cyclic addition of azide and olefin;
      construction of (pyrrolidine-2-ylidene)glycinate and glycinamides.
AB  - Oxopropyl E-(pyrrolidine-2-ylidene)glycinamide (5c) and allyl E-(pyrrolidine-2
      ylidene)glycinate (5d) were effectively synthesized from 2,3,5-tri-O-benzyl-4-O
      tert-butyldimethylsilyl(TBDMS)-D-arabinal (7) using intramolecular 1,3-dipolar
      cyclic reaction of azide and olefin as a key reaction. These results proved this
      cyclic reaction should be applicable for the synthesis of various (pyrrolidine-2
      ylidene)glycinate and glycinamide. In addition, the development of a synthetic
      route for the precursor of an unsaturated cyclic dehydro amino acid involved in
      azinomycins (carzinophilin) using relating glycinate, methyl E-(pyrrolidine-2
      ylidene)glycinate (5a) was described.

PMID- 15863926
TI  - Isomerization kinetics of panipenem in aqueous solution.
AB  - The isomerization kinetics of panipenem (INN: (+)-(5R,6S)-3-[(S)-1
      (acetimidoylpyrrolidin-3-yl)thio]-6-[(R)-hydroxyethyl]-7-oxo-1
      azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, CAS No. 87726-17-8) in aqueous
      solution were investigated. An equilibrium between the Z-form and E-form was
      observed, and it was found that the isomerization rates were affected by the pH
      of the solution. Under acidic conditions, the isomerization rates were small.
      However, the isomerization rates were increased with the pH value. This
      phenomenon resulted from the extent of proton dissociation from the acetimidoyl
      group.

PMID- 15863927
TI  - Synthesis of optically active vomifoliol and roseoside stereoisomers.
AB  - A synthesis of optically active vomifoliol stereoisomers 1-4 and their
      glucosides, roseoside stereoisomers 5-8, was accomplished via alpha-acetylenic
      alcohol 11a or 11b effectively prepared by an asymmetric transfer hydrogenation
      of alpha,beta-acetylenic ketone 10. Simultaneous separation of these
      stereoisomers by HPLC was also performed.

PMID- 15863928
TI  - Preparative monohydroxyflavanone syntheses and a protocol for gas chromatography
      mass spectrometry analysis of monohydroxyflavanones.
AB  - We describe a facile efficient, and preparative approach for monohydroxyflavanone
      syntheses. Using this protocol, a hydroxyl is regio-selectively introduced at one
      carbon of a flavanone A- or B-ring per synthesis. The seven possible isomers were
      each synthesized from the corresponding monomethoxymethoxylated 2'
      hydroxychalcones in acidic solution. These monohydroxyflavanones were
      characterized using a gas chromatography-mass spectrometry (GC-MS) system that
      incorporated a DB-5 capillary column. Ours is the first report of a preparative
      synthetic method during which a single hydroxyl can be selectively added to a
      flavanone A- or B-ring at any position. We are also the first to develop a
      procedure that separates the seven isomers by GC and characterizes the mass
      spectra of the isomers. Both the synthetic method and the GC-MS conditions may
      become important tools during future flavanone metabolism and oxidation studies.

PMID- 15863929
TI  - Synthesis of poison-frog alkaloids 237D, 207A, and two congeners of 235B' for
      evaluation to inhibitory effect of nicotinic acetylcholine receptors.
AB  - Enantioselective synthesis of the poison-frog alkaloids 237D, 207A, and two
      congeners of 235B' has been achieved. The absolute stereochemistry of 237D was
      determined to be 5S, 8S, 9R by the present synthesis.

PMID- 15863930
TI  - Antimutagenic constituents from the thorns of Gleditsia sinensis.
AB  - Antimutagenic activity-guided fractionation of an extract prepared from the
      thorns of Gleditsia sinensis LAM. led to the isolation of one triterpenoid and
      four steroids, which were identified as D:C-friedours-7-en-3-one (1), stigmast-4
      ene-3,6-dione (2), stigmastane-3,6-dione (3), stigmasterol (4), and beta
      sitosterol (5). Triterpenoid 1 was found for the first time in a natural source
      and the steroids 2-5 were first isolated from this plant. Stigmasterol was the
      most active antimutagen, showing 51.2% and 64.2% reduction of the induction
      factor against the mutagens MNNG and NQO, respectively, in the SOS chromotest.
      Some NMR data of the steroids 2 and 3 obtained have to be revised.

PMID- 15863931
TI  - Enzymatic resolution of (+/-)-5-acetoxy-4-aryl-(2E)-pentenoate derivatives.
AB  - Enzymatic resolution of six (+/-)-5-acetoxy-4-aryl-(2E)-pentenoate derivatives,
      compounds 9, 11, 13, 15, 17, and 19 bearing a different aromatic substitution
      pattern, using lipase OF-360 from Candida rugosa was carried out. The absolute
      configurations of all hydrolyzed products and all unchanged acetates were found
      to be S and R, respectively. Moreover, the enantiomeric excess of the enzymatic
      resolution products from 9, 11, and 13 with the ortho-methoxyl group in the
      aromatic ring was higher than that of the substrates with no methoxyl group at
      the ortho-position in the aromatic ring.

PMID- 15863932
TI  - Haloxylines A and B, antifungal and cholinesterase inhibiting piperidine
      alkaloids from Haloxylon salicornicum.
AB  - Haloxylines A (1) and B (2), new piperidine alkaloids, have been isolated from
      the chloroform soluble fraction of Haloxylon salicornicum and their structures
      elucidated by spectroscopic techniques including 2D-NMR. Both the compounds
      displayed antifungal and cholinesterase enzymes inhibitory potentials.

PMID- 15863933
TI  - Simultaneous determination of anthraquinones, their 8-beta-D-glucosides, and
      sennosides of Rhei Rhizoma by capillary electrophoresis.
AB  - The simultaneous separation and determination of major anthraquinones (emodin,
      chrysophanol, rhein and their glucosides, aloe-emodin, sennoside A, and sennoside
      B) of Rhei Rhizoma were achieved by cyclodextrin modified capillary zone
      electrophoresis. The running electrolyte used in this method was 0.005 M alpha
      cyclodextrin in 0.03 M borate buffer (pH 10.0) containing 20% acetonitrile, with
      an applied voltage of 20 kV.

PMID- 15863934
TI  - Isotope effects in the reaction of benzo[h]quinoline N-oxides with methylsulfinyl
      carbanion examined by ab initio molecular orbital methods.
AB  - The reactions of benzo[h]quinoline N-oxide with methylsulfinyl carbanion and
      deuterated methylsulfinyl carbanion, respectively, were studied theoretically.
      Differences in yield between these reactions were explained using ab initio
      molecular orbital methods by considering the zero-point energy correction and the
      barrier penetration effect. In these reactions, two transition states affected
      the total reaction rate. The hydrogen- or deuterium-transfer step played a
      significant role, accounting for the difference in reaction rates.

PMID- 15863935
TI  - Acetophenone diglycosides from Erythroxylum cambodianum.
AB  - Two new acetophenone diglycosides, erythroxylosides A and B, were isolated from
      the aerial portion of Erythroxylum cambodianum together with (+)-catechin, (-)
      epicatechin, quercetin 3-O-rutinoside, (3S,5R,6R,7E,9S-megastigman-7-ene-3,5,6,9
      tetrol 3-O-beta-D-glucopyranoside and citroside A. The structural elucidations
      were based on analyses of chemical and spectroscopic data.

PMID- 15863936
TI  - Cordycedipeptide A, a new cyclodipeptide from the culture liquid of Cordyceps
      sinensis (Berk.) Sacc.
AB  - A new cyclodipeptide named as cordycedipeptide A, a new natural compound and two
      known compound were isolated from the culture liquid of Cordyceps sinensis
      (BERK.) SACC. Their structures were elucidated as 3-acetamino-6-isobutyl-2,5
      dioxopiperazine (1), 3-isopropyl-6-isobutyl-2,5-dioxopiperazine (2) and 3,6-di(4
      hydroxy)benzyl-2,5-dioxopiperazine (3) by 1D and 2D-NMR techniques. The cytotoxic
      assay showed compound 1 had the cytotoxic activities to L-929, A375, and Hela.

PMID- 15863937
TI  - A new tomato pregnane glycoside from the overripe fruits.
AB  - A new pregnane glycoside has been isolated from the overripe fruits of Cherry
      tomato (Mini tomato), Lycopersicon esculentum var. cerasiforme (DUNAL) ALEF. The
      structure was determined to be 3-O-beta-lycotetraosyl 3beta-hydroxy-5alpha-pregn
      16-en-20-one on the basis of spectroscopic analysis. The seasonal variation of
      the tomato saponin is discussed.

PMID- 15863938
TI  - Mechanistic aspects of thiyl radical-promoted acyl radical cyclization of
      formylenoate-cyclization versus oxidation.
AB  - Treatment of formylalkenoates 1 and 7 with 2,2'-azobis(2-methylpropanenitrile)
      (AIBN) in the presence of dioxygen gave oxygenated carboxylic acids 5, 6, 8, 9
      instead of acyl radical cyclization products, through preferential reaction of
      the corresponding acyl radicals with dioxygen rather than intramolecular attack
      to an enoate moiety. The reaction of 1 with AIBN in the absence of dioxygen
      recovered starting 1 in 98% yield.

PMID- 15863939
TI  - Stereoselective synthesis of methyl (Z)-(4,4-difluoro-2,3,4,5-tetrahydro-1H-1
      benzazepin-5-ylidene)acetate using a dianion Horner-Wadsworth-Emmons reagent.
AB  - Stereoselective synthesis of methyl (Z)-(4,4-difluoro-2,3,4,5-tetrahydro-1H-1
      benzazepin-5-ylidene)acetate (1a) is described. Z-selectivity of the Horner
      Wadsworth-Emmons (HWE) reaction was obtained based on an investigation of the
      reaction conditions for introduction of a methylidene group onto the 5-position
      of benzazepine.

PMID- 15863940
TI  - Flavonol glycosides in leaves of two Diospyros species.
AB  - Fourteen flavonol glycosides including two new compounds were isolated from the
      leaves of two Diospyros plants (D. cathayensis and D. rhombifolia). The
      structures of isolated compounds were determined by spectroscopic analysis. The
      scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical of the
      isolated compounds was also investigated.

PMID- 15863941
TI  - New bisindole alkaloids isolated from Myxomycetes Arcyria cinerea and Lycogala
      epidendrum.
AB  - Two new bisindole alkaloids, named cinereapyrrole A (1) and B (2), were isolated
      from wild fruit bodies of Arcyria cinerea and three new bisindole alkaloids (3-5)
      were isolated from wild fruit bodies of Lycogala epidendrum. Seven known
      bisindoles (6-12) were concomitantly obtained from them. The structures of the
      new compounds were elucidated by spectral data. Among these bisindole alkaloids,
      compound 12 showed cytotoxicity against cultured tumor cell lines.

PMID- 15863942
TI  - Molecular mechanism of action of selective estrogen receptor modulator in target
      tissues.

PMID- 15863943
TI  - Comparison of the function of the beta(C) and beta(E) subunits of activin in
      AML12 hepatocytes.
AB  - To investigate the function of the beta(C) and beta(E) subunits of activin, we
      overexpressed these subunits in AML12 cells, a normal hepatocyte cell line, using
      adenovirus vector. Overexpression of the beta(C) subunit increased [3H]thymidine
      incorporation and the cell number. In contrast, both [3H]thymidine incorporation
      and the cell number were reduced in the beta(E) overexpressing cells. When AML
      cells overexpressing the beta(E) subunit were cultured in medium containing 1%
      serum for 48 h, many of the cells died by apoptosis, whereas cells overexpressing
      the beta(C) subunit or beta-galactosidase survived in the same condition. To
      examine dimer formation, the beta(C) and beta(E) subunits were expressed in AML12
      cells. In these cells, the beta(C) homodimer, the beta(E) homodimer and the
      beta(C)-beta(E) heterodimer were detected. When the expression level of the
      beta(E) subunit was increased, formation of the beta(E) homodimer was increased,
      while formation of the beta(C)-beta(E) heterodimer was slightly reduced.
      Overexpression of the beta(E) subunit did not significantly affect the formation
      of the beta(C) homodimer. These results indicate that the beta(C) and beta(E)
      subunits form homo- and heterodimers, and that the functions of the two subunits
      are quite different.

PMID- 15863944
TI  - Thyroid evaluation in patients with primary hyperparathyroidism.
AB  - We evaluated the efficacy of preoperative high-resolution ultrasonography (US)
      for diagnosing possible concomitant thyroid disease which affects the surgical
      management in patients with primary hyperparathyroidism (pHPT). One hundred and
      nine patients with sporadic pHPT underwent US with or without ultrasound-guided
      fine-needle aspiration biopsy (US-FNAB). Diagnosis of concomitant thyroid nodules
      by US and US-FNAB were compared with the histopathological findings. Of the 109
      patients, 19 (17.4%) had malignant thyroid nodules, 26 (23.9%) had benign thyroid
      nodules alone, and 12 (11.0%) had diffuse goiter. The sensitivity, specificity,
      and accuracy of diagnosing 72 thyroid nodules were 91.3%, 91.8%, and 91.7% for
      US, 57.9%, 94.3%, and 81.5% for US-FNAB, and 95.7%, 91.8%, and 93.1% for combined
      US and US-FNAB, respectively. True positive/false negative ratio of US-FNAB
      diagnosis was significantly lower in nodules of 5-9 mm than nodules of 10 mm or
      more. Four unexpected thyroid cancers existed at a different site in 3 of the 39
      patients with palpable thyroid disease. Five thyroid cancers were
      histopathologically confirmed in 5 (7.1%) of 70 patients without palpable thyroid
      disease. Eight (88.9%) of the 9 non-palpable thyroid cancers were accurately
      diagnosed by combined US and US-FNAB. Preoperative US is useful for evaluation of
      possible concomitant thyroid disease, especially for prediction of malignancy.

PMID- 15863945
TI  - Investigation of the hypothalamo-pituitary-adrenal axis and changes in the size
      of adrenal glands in acute brucellosis.
AB  - The aim of the study was to investigate the hypothalamo-pituitary-adrenal (HPA)
      axis by ACTH stimulation test and the changes in adrenal size in acute
      brucellosis before and after therapy in a prospective study. Sixteen patients
      with acute brucellosis and 15 healthy subjects were included in the study during
      the last two years. Cortisol levels were assessed before, 30 and 60 minutes after
      ACTH (250 microg i.v.) injection and the size of the adrenals was measured in
      both groups. Mean basal cortisol levels in the patients before the therapy and
      after the therapy were 22.1 +/- 6.9 microg/dL and 11.3 +/- 6.0 microg/dL,
      respectively. The difference was statistically significant (p<0.001). There was
      also statistically significant difference for basal cortisol levels between the
      healthy subjects (12.2 +/- 4.6 microg/dL) and the patients before the therapy
      (p<0.001). Peak cortisol responses to ACTH were higher before the therapy in the
      patients with acute brucellosis (39.3 +/- 10.7 microg/dL) than in the healthy
      subjects (30.4 +/- 4.8 microg/dL, p = 0.014). However, there was no significant
      difference for peak cortisol levels in the patients before and after the therapy
      (32.7 +/- 8.0 microg/dL). Mean basal cortisol levels and peak cortisol responses
      to ACTH between the patients after the therapy and the healthy controls were
      similar. Both the maximum width of the adrenal glands and the width of the
      adrenal limbs were significantly greater before the therapy compared to healthy
      subjects and post-treatment period. We concluded that the HPA axis is activated
      and the adrenal glands are enlarged in acute brucellosis, which is reduced after
      appropriate therapy.

PMID- 15863946
TI  - Utility of computed tomography in identifying an ectopic thyroid in infants and
      pre-school children.
AB  - In purpose of identifying thyroid tissue in patients with congenital
      hypothyroidism during childhood, ultrasonography is usually used as a screening
      examination, and scintigraphy is performed secondarily. Though these methods are
      useful, it is not easy to identify the accurate location of thyroid tissue by
      these methods. We previously reported the utility of computed tomography (CT) in
      identifying thyroid tissue in four cases of congenital hypothyroidism. The
      purpose of this study is to investigate whether CT is useful in identifying
      thyroid tissue, compared to ultrasonography or scintigraphy. Nineteen cases (0
      month to 18 years of age) that were suspected to have ectopic thyroid tissue or
      thyroid agenesis on ultrasonography were examined by CT. CT was useful in
      diagnosing ectopic thyroid tissue or thyroid agenesis in all the cases, whereas
      ultrasonography or scintigraphy was less accurate in this purpose in seven cases.
      Plain CT had a difficulty in identifying thyroid tissue in two cases, in which
      contrasted image was required. This study showed that CT, especially an enhanced
      CT, is useful in identifying thyroid tissue, when the gland is not identified in
      the normal position by ultrasonography.

PMID- 15863947
TI  - Systemic inflammatory syndrome and hepatic inflammatory cell infiltration caused
      by an interleukin-6 producing pheochromocytoma.
AB  - Pheochromocytoma is a tumor that produces a variety of biologically active
      substances in addition to catecholamines. We report here a patient with a
      pheochromocytoma, who presented with acute inflammatory symptoms and marked
      abnormalities in liver function and hematological tests. A 31-year-old man, who
      had experienced intermittent fever, chills and weight loss during the previous
      several months, was referred to our hospital for further evaluation. Laboratory
      examination revealed anemia, leukocytosis with elevated inflammatory markers, and
      abnormalities in coagulation and liver function tests. Histological examination
      revealed a marked plasmacytosis in the bone marrow and lymphocyte infiltration
      into the portal area of the liver. Along with increases in serum catecholamine
      and urine catecholamine metabolites, his serum interleukin (IL)-6 level was
      increased to 300 pg/ml, compared with a normal range of 3-12 pg/ml. Left
      adrenalectomy was performed. The adrenal tumor was densely immunostained with
      antibody to IL-6. After resection of his adrenal tumor, his serum IL-6 level
      returned to normal (11 pg/ml) and all symptoms subsided with normalization of
      laboratory findings.

PMID- 15863948
TI  - Comparison of the complications of subtotal, near total and total thyroidectomy
      in the surgical management of multinodular goitre.
AB  - Purpose of the study is to compare complication rates of bilateral subtotal
      (BST), near total (NTT) and total thyroidectomy (TT) in a cohort of patients
      undergoing surgery for benign multinodular goitre (MNG). Seven hundred and fifty
      patients undergoing surgery for MNG were studied with a median follow-up of 53
      months (range 18-102). There was no operative mortality in this group and no
      patients required urgent re-exploration for haematoma. After BST 14 patients
      (14/170 - 8.2%) developed transient hypocalcaemia and 4 patients (4/170 - 2.4%)
      had transient and one permanent (1/170 - 0.6%) recurrent laryngeal nerve (RLN)
      palsy. In NTT group 39 patients (39/320 - 12.2%) developed transient
      hypocalcaemia and 2 patients (0.6%) transient voice disturbances. None of the
      patients in this group experienced permanent complications. However, in TT group
      78 patients had (78/260 - 30%) transient hypocalcaemia whereas only one patient
      (1/260 - 0.4%) suffered permanent hypoparathyroidism and 5 patients (5/260 -
      1.9%) had temporary RLN injury but none of them remained permanent. There are
      only 2 (2/170 - 1.2%) recurrences and those patients are in BST group. All of the
      patients in BST group required at least 100 microg of thyroxine supplementation
      following the operation. These results demonstrate low permanent complication
      rates following thyroid surgery. Although the incidence of transient
      hypoparathyroidism increases with the extent of the resection, permanent
      complication rates are similar for all three surgical procedures. Even with short
      follow-up, there is a risk of recurrence with BST and therefore NTT or TT may be
      the operation of choice for MNG.

PMID- 15863949
TI  - Diagnosis of thyroid follicular carcinoma by the vascular pattern and
      velocimetric parameters using high resolution pulsed and power Doppler
      ultrasonography.
AB  - The aim of this study was to define the preoperative diagnosis of thyroid
      follicular carcinoma by the vascular pattern and velocimetric parameters using
      high resolution pulsed and power Doppler ultrasonography (US). We compared the
      vascular pattern and the velocimetric parameters, such as peak systolic velocity
      (Vmax), end-diastolic velocity (Vmin), pulsatility index (PI), or resistance
      index (RI) between follicular adenoma (FA, n = 25) and follicular carcinoma (FC,
      n = 10) and analysed them by means of receiver characteristics curves (ROC). Of
      10 patients with FC, 8 (80%) patients presented a moderate increase of
      intranodular vascularization using power Doppler US. In contrast, the majority
      (84%, 21 out of 25 cases) of FA cases showed only a peripheral rim of color flow
      even by power Doppler US. These color flow imagings by power Doppler US were
      suggested to be a reliable tool for the differential diagnosis of thyroid
      follicular tumor with a sensitivity of 87.5% and a specificity of 92%. In
      velocimetric analyses, the Vmax/Vmin ratios, PI, and RI were significantly higher
      in the patients with FC than those with FA (p<0.001, p<0.005, and p<0.001,
      respectively). By means of ROC, FC could be diagnosed with a cutoff value of
      ratio of PI (>1.35), RI (>0.78), and Vmax/Vmin (>3.79). The diagnostic efficiency
      evaluated by ROC curves were 0.898 for PI, 0.876 for RI, and 0.888 for Vmax/Vmin,
      respectively. In conclusion, the evaluation of the vascular pattern and the
      velocimetric parameters using pulsed and power Doppler ultrasound may provide
      important information that is useful in making correct differential diagnosis of
      malignant or benign thyroid follicular tumor preoperatively.

PMID- 15863950
TI  - TSH influences serum leptin levels independent of thyroid hormones in hypothyroid
      and hyperthyroid patients.
AB  - Leptin is considered to play a role in maintenance of energy balance and body
      weight by neuroendocrine mechanisms. The physiological mechanisms for thyroid
      hormone-induced alteration in serum leptin are not well known. In the present
      study, the relationship between thyroid hormones and leptin levels was
      investigated in patients with overt hypothyroidism and hyperthyroidism before and
      after successful treatment. Leptin levels were determined by radioimmunoassay and
      body mass index (BMI) was calculated for each subject. Serum leptin levels of 26
      hypothyroid and 22 hyperthyroid patients were compared with those of 20 healthy
      volunteers who comprised the controls. Serum leptin levels of hypothyroid
      patients (28.4 +/- 4.1 ng/ml) were found to be significantly higher than the
      controls (19.1 +/- 3.2 ng/ml) (p<0.01), whereas hyperthyroid patients had lower
      levels (10.7 +/- 1.2 ng/ml) (p<0.01). In hypothyroid patients, serum leptin
      levels were decreased significantly to 20.6 +/- 2.1 ng/ml with thyroxin treatment
      (p<0.05). However, in hyperthyroid group, serum leptin levels were increased to
      12.4 +/- 2.2 ng/ml by treatment (p>0.05). BMI was not changed with the treatment
      in either group. The serum leptin levels were correlated with BMI and thyrotropin
      (TSH) in both hypothyroid and hyperthyroid patients. Serum leptin levels are
      affected in thyroid disorders and the correlation of leptin with TSH is
      independent of thyroid hormones.

PMID- 15863951
TI  - A case of postpartum hypopituitarism accompanied by Cushing's syndrome as a
      result of an adrenocortical carcinoma.
AB  - Sheehan's syndrome frequently causes hypopituitarism either immediately or after
      a delay of several years, depending on the degrees of postpartum ischemic
      pituitary necrosis. A 55 year-old woman whose last child was born 27 yr ago with
      massive hemorrhage was diagnosed as postpartum hypopituitarism. She had
      deficiency of growth hormone, prolactin, gonadotropins and thyrotropin. However,
      she interestingly had apparent hypercortisolism without suppression response to
      the dexamethasone tests. We found an adrenal mass with distant metastases to the
      liver and lung while investigating the origin of the hypercortisolism.
      Hyperandrogenism and very high levels of 17alpha hydroxyprogesterone were
      present. Accordingly, the patient was diagnosed as hypopituitarism due to
      Sheehan's syndrome accompanied by Cushing's syndrome as a result of an
      adrenocortical carcinoma.

PMID- 15863952
TI  - Comparison of histological findings and parathyroid scintigraphy in hemodialysis
      patients with secondary hyperparathyroid glands.
AB  - To determine the usefulness of parathyroid scintigraphy in histological
      estimation for secondary hyperparathyroidism (2HPT) using Tc-99m sestamibi or Tc
      99m tetrofosmin. Tc-99m sestamibi (MIBI) and Tc-99m tetrofosmin (Tetro)
      parathyroid imaging following double-phase study, magnetic resonance imaging
      (MRI), and ultrasound were performed on 14 patients with 2HPT. All patients
      underwent parathyroidectomy. The uptake of two tracers in parathyroid areas was
      compared with the histopathologic findings. Forty-nine parathyroid glands were
      surgically explored and histologically proven to be hyperplastic. Of these, 42
      were diagnosed with nodular type (N-type) hyperplasia, and 7 with diffuse type (D
      type) hyperplasia. MIBI and Tetro parathyroid imagings detected 34 and 35
      parathyroid glands, respectively. The sensitivity of MIBI was determined to be
      76.2% (32/42) for N-type, and 28.6% (2/7) for D-type. The sensitivity of Tetro
      was determined to be 78.6% (33/42) for N-type and 28.6% (2/7) for D-type. The
      sensitivity of both MIBI and Tetro was significantly higher for N-type than for D
      type, 76.2% (32/42) vs. 28.6% (2/7) in MIBI, P = 0.022; 78.6% (33/42) vs. 28.6%
      (2/7) in Tetro, P = 0.015. The sensitivity of MRI was determined to be 76.2%
      (32/42) for N-type and 42.9% (3/7) for D-type, and the sensitivity of ultrasound
      was 71.4% (30/42) for N-type and 71.4% (5/7) for D-type. There was no significant
      difference in the sensitivity of MRI or ultrasound between N-type and D-type. The
      uptake ratios of MIBI and Tetro were also greater for N-type than for D-type. The
      detectability of both MIBI and Tetro was greater for N-type than for D-type. Tc
      99m MIBI or Tc-99m Tetro parathyroid scintigraphy therefore may be used
      clinically to distinguish N-type from D-type parathyroid gland hyperplasia.

PMID- 15863953
TI  - Clinical usefulness of the thickness of preperitoneal and subcutaneous fat layer
      in the abdomen estimated by ultrasonography for diagnosing abdominal obesity in
      each type of impaired glucose tolerance in man.
AB  - For this study we enrolled 1,615 males who were admitted to our hospital for a
      general health check-up. Plasma glucose (PG) and insulin were measured during 75
      g OGTT, and abdominal obesity was assessed by ultrasonography in all subjects. We
      divided them into several groups: normal glucose tolerance (NGT), high-normal
      glucose tolerance (h-NGT) who showed >10.0 nmol/l at 1 hr PG among those with
      NGT, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG + IGT,
      and DM, according to the results of 75 g OGTT. The aim of the present study was
      to clarify the clinical characteristics of pre-diabetic disorders relating to
      metabolic syndrome by comparing various parameters including body mass index
      (BMI), blood levels of various lipids and abdominal wall fat index (AFI)
      calculated from the thickness of preperitoneal (Pmax) and subcutaneous (Smin) fat
      layer in the abdomen estimated by ultrasonography with insulin sensitivity
      determined by homeostatic model assessment (HOMA-IR) in each type of abnormal
      glucose regulation as classified by PG changes in 75 g OGTT. We also investigated
      the relationship between insulin secretion capability and insulin sensitivity to
      delineate the characteristics of each type of abnormal glucose regulation, and
      compared the area under the insulin curve (AUCins) and the time axis, and the
      ability of early insulin secretion by glucose loading (insulinogenic index: I.I.)
      in each type of abnormal glucose regulation. There was a significant positive
      correlation between HOMA-IR and Smin or Pmax, suggesting that Smin and Pmax may
      reflect insulin sensitivity. Abdominal obesity, which was diagnosed from the data
      of AFI, was present in the h-NGT and IFG + IGT groups, suggesting that those
      groups belong to the clinical entity of metabolic syndrome. HOMA-IR was higher in
      IFG than in IGT, although I.I. was reduced and AUCins was increased in IFG as
      well as in IGT. h-NGT demonstrated a slightly lower I.I. and higher AUCins,
      compared with IGT. IFG demonstrated much stronger insulin resistance than IGT,
      although I.I. was reduced and AUCins was increased in IFG and IGT. Thus, it is
      suggested that insulin sensitivity may partly account for the difference in
      pathogenesis between IFG and IGT; and that h-NGT, which showed abdominal obesity
      assessed as AFI by ultrasonography, should be recognized as a disease state of
      metabolic syndrome with impaired glucose regulation.

PMID- 15863954
TI  - Reevaluation of stringent low iodine diet in outpatient preparation for
      radioiodine examination and therapy.
AB  - To decrease total body iodine is a key point in preparation for radioiodine study
      and therapy. We introduced a stringent self-managed low iodine diet (LID) and
      compared the outcome to that of the conventional restricted iodine diet (RID) for
      outpatients. We measured urine iodine to creatinine ratios (I/Cr) in patients
      prepared with RID for one week, LID for one week, or LID for two weeks. Mean
      urinary iodine excretion after RID for one week (n = 210) was 182.2 microg/gCr
      (range, 13-986 microg/gCr; standard deviation (SD) = 158.5) not reaching below
      the recommended level (I/Cr<100 microg/gCr). Urinary iodine excretion after LID
      for one week (n = 15) showed a lower mean urinary iodine level (I/Cr 119.4
      microg/gCr; range, 23-218 microg/gCr; SD = 55.9) than RID for one-week, and two
      week LID (n = 17) showed an even lower mean level (I/Cr 63.1 microg/gCr; range, 7
      134 microg/gCr; SD = 38.7). The one-week LID period adequately (recommended level
      of I/Cr being less than 100 microg/gCr) prepared 26% of the patients, while two
      weeks on the diet adequately prepared 70% of the patients. Furthermore, none of
      the two-week LID patients had I/Cr>150 microg/gCr, although a significantly
      greater number of one-week LID patients (19%) did. Our self-managed, outpatient
      LID successfully induced iodine deficiency, and two-week LID may be recommended
      for preparation in radioiodine study and therapy for thyroid cancer.

PMID- 15863955
TI  - Adiponectin levels and cardiovascular risk factors in Japanese men with type 2
      diabetes.
AB  - Several cardiovascular risk factors correlate with adiponectin levels. It is not
      known whether total homocysteine, folate and gamma-glutamyl transferase levels
      correlate with adiponectin. We cross-sectionally analyzed the association between
      adiponectin and these cardiovascular risk factors in diabetic patients. One
      hundred and two male inpatients with type 2 diabetes without overt nephropathy or
      insulin use were studied. In a regression analysis of the quartiles of
      adiponectin, plasma levels of adiponectin were associated positively with HDL
      cholesterol and age, and inversely with body mass index and HbA1c, but not with
      total homocysteine, folate or gamma-glutamyl transferase. Non-traditional
      cardiovascular risk factors such as homocysteine and folate levels were not
      associated with adiponectin levels in male type 2 diabetic patients who are not
      subject to insulin therapy.

PMID- 15863956
TI  - Progesterone receptor subtypes in vascular smooth muscle cells of human aorta.
AB  - Progesterone is involved in various functions of the cardiovascular system,
      including those of vascular smooth muscle cells (VSMCs) via progesterone receptor
      (PR). Progesterone has also been postulated to be involved in inhibition of VSMC
      proliferation via PR. However, the details of PR expression have remained largely
      unknown in human cardiovascular VSMCs. Therefore, we first examined the relative
      levels of PR isoform (PR-A and PR-B) expression in VSMCs, using both
      immunohistochemistry and quantitative RT-PCR analysis. PR-B was equally expressed
      between male and female aorta, but PR-A was more abundant in female than in male
      aorta. This finding demonstrated that the status of PR subtype expression was
      associated with the difference of genders.

PMID- 15863957
TI  - Quantitative insulin sensitivity check index is a useful indicator of insulin
      resistance in Japanese metabolically obese, normal-weight subjects with normal
      glucose tolerance.
AB  - To clarify whether quantitative insulin sensitivity check index (QUICKI) is
      useful as an indicator of insulin resistance in Japanese metabolically obese,
      normal-weight (MONW, body mass index (BMI) <25 and visceral fat area (VFA) > or =
      100 cm2 by abdominal computed tomography scanning) subjects with normal glucose
      tolerance (NGT). Insulin resistance was measured by QUICKI and euglycemic
      hyperinsulinemic clamp study (clamp IR) in 27 MONW and 27 normal subjects (BMI
      <25 and visceral fat area <100 cm2). QUICKI (P<0.01) and clamp IR (p<0.01) were
      significantly decreased in MONW subjects compared with normal subjects. QUICKI
      was significantly associated with VFA [MONW subjects: r = -0.459, p<0.02; all
      (MONW and normal) subjects: r = -0.506, p<0.0001] and with the serum levels of
      triglycerides (MONW subjects: r = -0.386, p<0.05; all subjects: r = -0.505,
      p<0.001) in MONW and all subjects. There were significant correlations between
      clamp IR and VFA (MONW subjects: r = -0.562, p<0.01; all subjects: r = -0.575,
      p<0.0001), fasting serum levels of insulin (MONW subjects: r = -0.673, p<0.001;
      all subjects: r = -0.619, p<0.0001) or serum levels of triglycerides (MONW
      subjects: r = -0.485, p<0.02; all subjects: r = -0.565, p<0.0001) in MONW and all
      subjects. QUICKI was significantly correlated with clamp IR in MONW (r = 0.754,
      p<0.0001) and in all subjects (r = 0.568, p<0.0001). QUICKI may be an useful
      method for assessing insulin resistance in Japanese MONW subjects with NGT.

PMID- 15863958
TI  - Anti-oxidative effect of fluvastatin in hyperlipidemic type 2 diabetic patients.
AB  - An open-label prospective cross-over trial was performed to evaluate the
      antioxidative effect of fluvastatin in Japanese type 2 diabetics with
      hyperlipidemia. The study subjects were 10 patients who were on pravastatin (10
      mg/day) or simvastatin (5 mg/day). After at least 12 weeks of continuous
      pravastatin or simvastatin therapy, the drugs were washed out for 12 weeks and
      replaced with fluvastatin (30 mg/day), then the treatment was continued for
      another 12 weeks. Total cholesterol and LDL cholesterol were efficiently and
      comparably reduced by all three statin agents. There were no differences in serum
      parameters of oxidative stress such as malondialdehyde-modified low-density
      lipoprotein, thiobarbituric acid-reactive substances, and 8-iso-prostaglandin
      F2alpha between pravastatin/simvastatin and fluvastatin. However, fluvastatin,
      but not pravastatin/simvastatin, significantly reduced 3,5,7-cholestatriene in
      erythrocyte membrane, representing the extent of membrane cholesterol
      peroxidation. Our data demonstrated that fluvastatin has a unique anti-oxidative
      effect in patients with type 2 diabetes and hyperlipidemia, compared with other
      statins.

PMID- 15863959
TI  - Suppression of thyrotropin by morphine in a severely stressed patient.
AB  - Opiates suppress TSH in experimental animals but are reported to increase TSH in
      human subjects. We describe a patient in severe pain treated with morphine, whose
      previously normal TSH fell to a level usually associated with hyperthyroidism.
      After returning to a normal concentration, TSH again decreased with morphine
      administration. This suggests that, in contrast to the stimulation of TSH
      secretion that has been reported in unstressed experimental subjects, morphine
      can inhibit TSH secretion during stress in man as it does in experimental
      animals. This observation is consistent with the known sensitization of opiate
      receptors by stress. Consideration should be given to the possibility that severe
      suppression of TSH by opiates in stressed patients may induce clinically
      significant central hypothyroidism.

PMID- 15863960
TI  - Concentration of the n-octanoylated active form of ghrelin in fetal and neonatal
      circulation.
AB  - The octanoylation of Ser3 is essential for the biological function of ghrelin. We
      examined the concentrations of the n-octanoylated active-form ghrelin in cord and
      neonatal blood using an RIA system that specifically recognized n-octanoylated
      ghrelin, as well as a system that measured the total ghrelin concentration.
      Plasma levels of active ghrelin in cord blood ranged from 7.7 to 38.4 pmol/l and
      correlated excellently with those of total ghrelin (r = 0.81, p<0.0001). The
      active ghrelin/total ghrelin (A/T) ratio ranged from 0.038 to 0.12 (median
      0.072). The active ghrelin concentrations negatively correlated with birth body
      weight (r = -0.34, p = 0.01) and IGF-1 concentrations (r = -0.40, p = 0.003), but
      did not correlate with growth hormone (GH) concentrations. A considerable level
      of active ghrelin was detected in premature newborns. Venous cord blood samples
      showed a significantly higher active ghrelin concentration (p = 0.03) and A/T
      ratio (p = 0.01) than those in the artery. In neonatal blood, active ghrelin
      concentrations ranged from 4.6 to 22.6 pmol/l and the A/T ratio ranged from 0.02
      to 0.081. These results demonstrate the existence of active-form ghrelin in fetal
      and neonatal circulation and may suggest the energy supply-dependent regulation
      of ghrelin expression/secretion in utero.

PMID- 15863961
TI  - Octreotide as a rapid and effective painkiller for metastatic carcinoid tumor.
AB  - Octreotide is one of the somatostatin analogue used for the treatment of
      endocrine tumors principally to suppress hormone secretion and to inhibit tumor
      growth. We experienced a case with multiple endocrine neoplasia type 1 who small
      amount of octreotide dramatically relieved the lumber pain caused by metastatic
      bone tumor. He had recurrent bronchial carcinoid tumors that metastasized to
      liver and bones. The spontaneous and radiated pain by bone tumors subsided within
      a few minutes after the initial injection of octreotide and the effect persisted
      for several hours. Combination therapy of octreotide and interferon alpha-2b
      significantly reduced the size of metastatic liver tumors and inhibited further
      growth of metastatic bone tumors for the last 27 months. The use of octreotide
      may be a good option for controlling pain by metastatic bone disease and
      combination therapy of octreotide and interferon alpha-2b is worth to try for
      patients with inoperable metastatic carcinoid tumor.

PMID- 15863962
TI  - Synchronous occurrence of a follicular, papillary and medullary thyroid carcinoma
      in a recurrent goiter.
AB  - The simultaneous occurrence of different types of thyroid carcinoma in a single
      patient is an unusual event. We report the case of a 52-year-old man with the
      history of two previous thyroid operations for benign goiters, who developed a
      recurrent goiter. The patient was referred to our department for thyroidectomy.
      In the pathohistological examination the specimen showed a 5 cm follicular
      carcinoma and a 0.3 cm papillary microcarcinoma in the right lobe as well as a
      1.5 cm medullary carcinoma in the left lobe. All tumors were clearly separated
      from each other, representing the pure entity of each type. Postoperatively, RET
      germline mutation was ruled out by sequence analysis of peripheral blood
      leucocytes. Postoperative I-131-radioiodine scan showed multiple lung and liver
      metastases, while calcitonin was negative. There is no known common cause of
      these three different tumor types and they developed most independently from each
      other. The personal history of our patient was interesting in two aspects: (1) he
      suffered a period of severe staphylococcal sepsis with temporal immunosuppression
      and (2) he worked for long years as a coremaker in a foundry. This work
      represented possible long term exposure to inhalative carcinogenous toxins like
      hydrazine, which caused thyroid parafollicular cell adenomas in an animal model.

PMID- 15863963
TI  - [Overview: application of DNA chips to clinical immunology].
AB  - DNA microarrays or DNA chips are rapidly evolved technologies. Hybridization of
      labeled cDNA or cRNA to DNA probes on the solid phases enables analyses of
      transcriptome of particular cells. Storage and analysis of microarray data are
      also important factors. Several studies have been published on the gene
      expression in the immune cells during immune responses and immune mediated
      diseases.

PMID- 15863964
TI  - [Application to allergic diseases].
AB  - The increasing prevalence of allergic diseases in developed countries is
      considered to be caused, at least in part, by rapid improvement of human hygiene.
      In human beings, the immune system developed as an ingenious device for defending
      against frequent attacks by microbes. Therefore, our immune system seems to have
      become deranged in our recent, unprecedentedly hygienic environment. It is now
      necessary to understand the total functional elements comprising the immune
      system, not just a single molecule present in an immunocyte working in our immune
      system. Microarray analysis is now becoming capable of detecting the whole
      transcripts present in a cell. It is anticipated that we can understand the
      deranged human immunity using the system biology. It is also expected to predict
      previously unexpected drug-related adverse events caused by interaction of a drug
      with responsible molecules present in vital organs.

PMID- 15863965
TI  - [Appliance of microarray technology to clinical organ transplantation].
AB  - Although recent advances in immunosuppressive therapy have dramatically enhanced
      the early survival of solid organ transplant recipients, acute rejection still
      occurs in some recipients. Long-term immunosuppressive drug administration,
      furthermore, entails a number of potentially significant problems such as
      infection, spontaneous neoplasm and drug toxicity. Alloantigen specific tolerance
      induction is the ultimate goal in transplant immunology, and can be induced in a
      rodent model; however, the precise mechanism by which specific tolerance is
      affected are not clearly understood, and the current immunosuppression regimens
      have all failed to achieve this goal in a clinical setting. DNA microarray
      technology has made it possible to analyze the expression of a large number of
      genes and revolutionized many areas of biology and medicine. This new technology
      can provide non-biased, global expressions of tens of thousands of genes
      simultaneously. Recent studies on gene expression profiles in various diseases,
      including allograft rejection, have successfully provided important information
      and new insights into the biological mechanisms of these diseases. In this
      article, we reviewed these insights, especially with the viewpoint of appliance
      of microarray technology to clinical solid organ transplantation.

PMID- 15863966
TI  - [GeneChip analysis for osteoimmunology].
AB  - The interdisciplinary field called osteoimmunology has attracted much attention,
      due to the observations that bone destruction is caused by an abnormal activation
      of the immune system in rheumatoid arthritis, and mice lacking immunomodulatory
      molecules often exhibit an unexpected bone phenotype. Osteoclasts are cells of
      monocyte/macrophage origin that degrade the bone matrix in health and disease.
      Receptor activator of NF-kappaB ligand (RANKL), a tumor necrosis factor (TNF)
      family cytokine, is an essential osteoclastogenic factor linking the bone and the
      immune system. In the genomewide screening of RANKL-inducible genes using
      GeneChip, we identified nuclear factor of activated T cells c1 (NFATc1) as the
      master transcription factor for osteoclastogenesis. We also applied the GeneChip
      method to the analysis of osteoimmunological regulation: analysis of
      costimulatory signal for RANKL and the target genes of antirheumatic drugs. Here
      we summarize our recent findings in the field of osteoimmunology obtained by
      GeneChip.

PMID- 15863967
TI  - [Development of DNA array filter useful for the analysis of Th1/Th2 balance].
AB  - DNA arrays are useful for determining the expression levels of a number of genes
      at once. We utilized this technique to evaluate the Th1/Th2 balance in vivo.
      Immune responses are controlled by two types of helper T cells, Th1 and Th2. Once
      the balance of Th1/Th2 immunity is disrupted, various immune diseases can
      develop. Thus, it is important to evaluate the Th1/Th2 balance in each patient
      for diagnosis, treatment and/or prophylaxis of immune diseases. We have
      identified a number of genes specifically expressed in Th1 or Th2 cells, and
      developed a DNA array filter spotted with these genes. We confirmed that this
      filter is useful for the evaluation of changes in the immune balance in vivo.
      Clinical application of this technology may lead to the tailor-made therapy of
      immune diseases through the evaluation of the immune balance in each patient.

PMID- 15863968
TI  - [Thalidomide therapy for infantile-onset Crohn's disease].
AB  - A 6-month-old boy was diagnosed as having Crohn's disease (CD) by the endoscopic
      examination. Primary immunodeficiency syndrome was initially suspected due to a
      refractory infection that occurred just after birth and a family history that his
      older brother died at the age of 3 months of septicemia associated with
      perirectal abscess. Thalidomide was used because conventional medical treatment
      by steroids and immunosuppressives was ineffective. Thalidomide improved the
      symptoms of diarrhea, abdominal pain, high fever and fistula, and the PCDAI score
      decreased markedly from 45 to 15. Although thalidomide was discontinued after
      three months because of the onset of side effects, including edema, rash and the
      peripheral neuropathy, the effect on the fistula closure was maintained over a
      long period of time. Further studies will be necessary to determine the dosage of
      thalidomide that does not elicit side effects, but thalidomide seems to be
      effective in patients with refractory CD. Infantile CD is very rare and the
      diagnosis is often delayed. CD is generally resistant to medical treatment. More
      detailed information of infantile CD will be needed to elucidate the pathogenesis
      of this disease and progress of treatment. Recently the incidence of inflammatory
      bowel diseases has increased. CD should be suspected in any infant with the
      perianal lesion (fissures, fistula, skin tag and abscesses) especially when
      prolonged gastrointestinal symptoms, stomatitis or fever coexist.

PMID- 15863969
TI  - [Efficacy of anti-thymocyte globulin and cyclosporin A combined therapy in
      aplastic anemia complicated with limited cutaneous systemic sclerosis].
AB  - We reported here on a case of limited cutaneous systemic sclerosis (lcSSc) with
      aplastic anemia treated by anti-thymocyte globulin and cyclosporin A. The use of
      this therapy resulted not only in marrow recovery but also in resolution of the
      skin sclerosis. A 68 year-old woman was diagnosed as lcSSc accompanied by
      Hashimoto's thyroiditis and primary biliary cirrhosis. Treatment by D
      penicillamine was started. After 11 months, She complained of nasal bleeding and
      subcutaneous bleeding. Her laboratory data revealed pancytopenia. White blood
      cell count, hemoglobin concentration and platelet count were decreased at
      2300/microl, 8.2 g/dl, and 3000/microl respectively. Bone marrow was severely
      hypoplastic, suggesting aplastic anemia. The etiology of hypopastic marrow was
      considered to be D-penicillamine which had been frequently reported to cause
      hematopoietic cell suppression. We immediately started methylprednisolone pulse
      therapy combined with G-CSF and cyclosporin A, which showed little effectiveness.
      Next we tried the anti-thymocyte globulin therapy combined with G-CSF and
      cyclosporin A. Her blood cell counts gradually improved. After 4 months, she did
      not need the blood transfusion anymore. Furthermore, the sclerosis of her skin
      began to improve gradually, and the titer of anti-centromere antibody also
      decreased. Thus, anti-thymocyte globulin and cyclosporin A combined therapy can
      be considered among the therapies of systemic sclerosis.

PMID- 15863970
TI  - [Manifestations mimicking relapsing polychondritis in a patient with microscopic
      polyangiitis].
AB  - Microscopic polyangiitis (MPA) is a systemic disorder characterized by
      inflammation of small vessels mainly affecting the kidneys and lungs. We describe
      a 72-year-old woman who developed multiple cartilage involvements as well as
      major manifestations of MPA. The left ear biopsy demonstrated cartilaginous
      inflammation and small vessel vasculitis. She also had conjunctivitis, hearing
      impairment, interstitial lung disease, glomerulonephritis with vasculitis and
      mononeuritis multiplex. Serological examinations revealed a positive
      antineutrophil cytoplasmic antibody (PR-3 ANCA). Cyclophosphamide and oral
      corticosteroid therapy was instituted and remission achieved. Due to lacks of
      nasal and bronchial involvements, as well as the evidence of auricular
      vasculitis, we concluded that her findings mimicking relapsing polychondritis
      developed as systemic manifestations of MPA.

PMID- 15863971
TI  - Comparison of pharmaceutical properties of topical non-steroidal anti
      inflammatory drug preparations on quality of life.
AB  - To compare the effects of different pharmaceutical properties of commercially
      available topical nonsteroidal antiinflammatory drugs (NSAIDs) on the quality of
      life, we administered a questionnaire to 65 healthy volunteers. We investigated
      five creams, five gels, and four solutions of topical NSAID preparations in this
      study. The survey was conducted to clarify the relationship of their answers and
      pharmaceutical properties of the topical NSAID preparations. Questions addressed
      spreadability, smell, viscosity, and comfort level of the topical NSAID
      preparations. Among the five creams, Napageln had lower spreadability, less
      smell, and greater viscosity than the other preparations. Because of its easy
      spreadability, weak smell, and low viscosity, the volunteers favored Sector cream
      among the cream preparations. Among the five gel preparations, Inteban had less
      spreadability, stronger smell, and higher viscosity than the other preparations.
      The volunteers favored Epatec over the other gel preparations. All four solutions
      had the odor of menthol and other artificial ingredients, except for Napageln.
      These findings indicate that information on the pharmaceutical properties of
      commercially available topical NSAID preparations will be helpful to physicians
      and pharmacists in conducting medical treatment and prescribing.

PMID- 15863972
TI  - Establishment of pharmaceutical management for patient care during lung cancer
      chemotherapy and its quantitative evaluation.
AB  - Pharmacists should play an important role in controlling the pharmaceutical
      management of the patients. Although the quantitative evaluations of
      pharmaceutical management are required systematically, no guideline is presented
      for patient care during lung cancer chemotherapy. We established a complete
      pharmaceutical management system and evaluated the performance of the system.
      Patients admitted to Hokkaido Keiaikai Minami-ichijo Hospital for lung cancer
      chemotherapy treatment from 2003.5 to 2003.11 were enrolled in this study after
      signing formal written consents. The pharmaceutical management system that was
      established involves a unified system consisting of a standard care plan and
      worksheets by the Problem Oriented System (POS). The system can apply to
      inpatients for their comprehensive evaluation of pharmaceutical management. The
      incidence of pharmaceutical problems reported, pharmacist interventions to the
      physicians, and the bedside pharmaceutical management were increased
      significantly after applying the system. More than 98% acceptance of
      interventions by pharmacists to the physicians was indicated. A high rate of
      intervention for adverse drug reaction (ADR) was demonstrated, due to the
      information about patient conditions is essential in managing ADR. The total
      pharmaceutical management system established is expected to give quality
      improvements of pharmaceutical care along with its efficiency.

PMID- 15863973
TI  - Survey of the levels of satisfaction with pharmacy practice among third-year
      students in the Faculty of Pharmaceutical Sciences, Health Sciences University of
      Hokkaido--influence of experience in voluntary training at a community pharmacy
      and plans after graduation.
AB  - Pharmacy practice, which is executed in the taught of pharmaceutical sciences in
      Japan, has been assessed and improved student questionnaires. The levels of
      student satisfaction with the practice are expected to be influenced by their
      plans after graduation and their experience of training in pharmacies. However,
      there are few reports analyzing the information in the questionnaires from these
      viewpoints. In this report, we surveyed the levels of satisfaction of 148 third
      year students in the Faculty of Pharmaceutical Sciences of the Health Sciences
      University of Hokkaido using questionnaires and analyzed the influence of the
      students' background on the levels of satisfaction with pharmacy practice. Almost
      half of the students had received voluntary training in hospital and/or community
      pharmacies. Concerning plans after graduation, 36.5%, 27.7%, and 21.6% wanted to
      become community pharmacists, hospital pharmacists, and graduate students,
      respectively. More than 70% of the students were well satisfied with all the
      programs of practice. The levels of satisfaction with the overall practice and
      prescription analysis were significantly higher among students who had
      experienced training in pharmacies than among those who had not. Students who
      planned to become hospital pharmacists were more satisfied with manners seminars,
      one-dose package practice, and practice in a simulated pharmacy than the students
      who planned to enter the other field. Such surveys are useful for finding points
      for improvement and the development of new curricula when the assessment of
      pharmacy practice takes student background into consideration.

PMID- 15863974
TI  - Automation in drug inventory management saves personnel time and budget.
AB  - Automation in the drug distribution processes is helpful to pharmacists in
      creating new clinical services. We have ameliorated the drug inventory control
      system seamlessly connected with the physician order-entry system. This control
      system application, named Artima, allows inventory functions to be faster and
      more efficient in real time. The medicines used in our hospital are automatically
      fixed and arranged to sold-packages, and are ordered from each wholesaler by a
      fax-modem every day. Artima can search the lot number and expiration date of drug
      in the purchase and delivery records. These functions are powerful and useful in
      patient's safety and cost containment. We surveyed the inventory amount stored in
      the computer database, and evaluated time required for inventory management by
      tabulating working records of employees during past decades. Inventory decreased
      by 70% along with the continuous improvement of the system during the past
      decade. The workload in the inventory management in each section of the Pharmacy
      Department as well as in clinical units was dramatically reduced after the
      implementation of this system. The automation system in the drug inventory
      management allows creating new clinical positions for pharmacists. This system
      also could pay for itself in time.

PMID- 15863975
TI  - Preparation and clinical application of indomethacin gel for medical treatment of
      stomatitis.
AB  - The preparation and clinical applications of indomethacin (IM) gel were
      investigated in the treatment of stomatitis resulting from chemotherapy and
      radiotherapy for cancer. IM gel was prepared by adding various water-soluble
      polymers [hydroxypropyl cellulose (HPC), etc.] to IM aqueous solution. The
      release rate of IM from IM gels was found to decrease with increasing polymer
      concentration and viscosity and to follow a first-order reaction rate equation.
      The release rate of IM from the IM gel with HPC was decreased gradually with
      increasing polymer concentration and to be easily controllable compared with gels
      with other polymers. The time before pain relief occurred after application of
      the IM gel was slightly shorter and the duration of pain relief was longer
      compared with the IM aqueous solution. It was confirmed that IM gel is useful in
      the treatment of stomatitis.

PMID- 15863976
TI  - Evaluation of AUC(0-4) predictive methods for cyclosporine in kidney transplant
      patients.
AB  - Cyclosporine (CyA) is the most commonly used immunosuppressive agent in patients
      who undergo kidney transplantation. Dosage adjustment of CyA is usually based on
      trough levels. Recently, trough levels have been replacing the area under the
      concentration-time curve during the first 4 h after CyA administration (AUC(0
      4)). The aim of this study was to compare the predictive values obtained using
      three different methods of AUC(0-4) monitoring. AUC(0-4) was calculated from 0 to
      4 h in early and stable renal transplant patients using the trapezoidal rule. The
      predicted AUC(0-4) was calculated using three different methods: the multiple
      regression equation reported by Uchida et al.; Bayesian estimation for modified
      population pharmacokinetic parameters reported by Yoshida et al.; and modified
      population pharmacokinetic parameters reported by Cremers et al. The predicted
      AUC(0-4) was assessed on the basis of predictive bias, precision, and correlation
      coefficient. The predicted AUC(0-4) values obtained using three methods through
      measurement of three blood samples showed small differences in predictive bias,
      precision, and correlation coefficient. In the prediction of AUC(0-4) measurement
      of one blood sample from stable renal transplant patients, the performance of the
      regression equation reported by Uchida depended on sampling time. On the other
      hand, the performance of Bayesian estimation with modified pharmacokinetic
      parameters reported by Yoshida through measurement of one blood sample, which is
      not dependent on sampling time, showed a small difference in the correlation
      coefficient. The prediction of AUC(0-4) using a regression equation required
      accurate sampling time. In this study, the prediction of AUC(0-4) using Bayesian
      estimation did not require accurate sampling time in the AUC(0-4) monitoring of
      CyA. Thus Bayesian estimation is assumed to be clinically useful in the dosage
      adjustment of CyA.

PMID- 15863977
TI  - Effects of Coleus forskohlii on fat storage in ovariectomized rats.
AB  - The antiobesity effects of Coleus forskohlii were investigated in ovariectomized
      (ovx) rats. Eight-week-old female Wistar rats were assigned to four groups: a
      sham-operated group fed the control diet (MF, sham-m) ; an ovx-m group fed the
      control diet; a sham-operated group fed the control diet containing 50 g/kg of
      Coleus forskohlii extract (sham-c) ; and an ovx-c group fed the control diet
      containing 50 g/kg of Coleus forskohlii extract. The body weight, adipose
      tissues, and cell diameter were investigated in ovx rats after Coleus forskohlii
      extract treatment. Administration of Coleus forskohlii extracts reduced body
      weight, food intake, and fat accumulation in ovx rats. Our results suggest that
      Coleus forskohlii may be useful in the treatment of obesity.

PMID- 15863978
TI  - Investigation of mouth washing by patients after inhaling corticosteroids.
AB  - We report an effective method for mouth washing after inhalation of
      corticosteroids for the prevention of local adverse effects such as hoarseness
      and oropharyngeal candidiasis. This method involves gargling and rinsing
      immediately after inhalation, repeated at least twice. We performed a
      questionnaire survey on mouth washing after inhalation of corticosteroids of 19
      inpatients who used inhaled corticosteroids at the University of Tokyo Hospital.
      The questions concerned: 1) awareness of local adverse effects of inhaled
      corticosteroids; 2) gargling and rinsing habits; 3) repeating mouth washing at
      least twice; and 4) mouth washing immediately after inhalation. The percentage of
      patients correctly performing the individual maneuvers were: 1) 63.2%; 2) 36.8%;
      3) 36.8%; and 4) 63.2%. The percentage of patients performing our recommended
      method of mouth washing (all four elements) was 11%. These results suggest that
      patients receiving inhaled corticosteroids poorly comprehend mouth washing
      procedures after inhalation of corticosteroids. It is important that pharmacists
      advise patients on the correct method of mouth washing.

PMID- 15863979
TI  - Comparison of annual cost between brand and generic ocular beta-adrenergic
      blockers.
AB  - We conducted a study of the annual cost of various ophthalmic products used in
      Japan for treating glaucoma including six of brands and generic ocular beta
      adrenergic blockers (38 products). The total number of drops in one bottle of
      each solution was counted drop by drop. The cost per drop was calculated by
      dividing the government-controlled standard prices by the total number of drops
      in one bottle. The annual cost of ophthalmic solution was calculated by
      multiplying the cost per drop by the number of drops typically used per day. The
      total number of drops of the ophthalmic solutions in one bottle ranged from 108
      to 168. The yearly cost of the beta-adrenergic blockers studied ranged widely,
      from yen 5392 to yen 27236. Differences in the total number of drops and the
      usage effect on the annual cost of ophthalmic solutions were found. The annual
      cost depended on not only the price of the products but also on the total number
      of drops in one bottle and the usage. Annual cost data may be helpful in
      selecting ophthalmic products for treating glaucoma in Japan.

PMID- 15863980
TI  - Persistent elevation of C-reactive protein may predict cardiac hypertrophy and
      dysfunction in patients maintained on hemodialysis.
AB  - BACKGROUND: C-reactive protein (CRP), which reflects chronic inflammation, is a
      strong predictor of cardiovascular mortality in hemodialysis patients. We
      investigated whether persistent elevation of CRP is associated with cardiac
      function and morphology in patients maintained on hemodialysis. METHODS:
      Predialysis high-sensitivity CRP (hs-CRP) was measured twice at an interval of 3
      weeks in 52 stable hemodialysis patients, and echocardiographic studies were
      performed. RESULTS: 25 patients showed persistent elevation of predialysis hs-CRP
      (>3 mg/l, high CRP group). Patients in the high CRP group had a lower dialysis
      dose (p < 0.01), higher troponin T (p < 0.01), and higher fibrinogen (p < 0.01).
      Echocardiographic studies showed that left atrial diameter (LA, p < 0.05),
      interventricular septal thickness (IVST, p < 0.05), left ventricular end
      diastolic volume (LVEDV, p < 0.05), and left ventricular mass index (LVMI, p <
      0.05) were higher in the high CRP group. However the ejection fraction (EF) was
      lower in the high CRP group (p < 0.05), which also contained more patients with
      low EF (<40%) (p < 0.01). There was no difference in diabetes mellitus, acute
      infection and type of vascular access between the groups. hs-CRP level was
      positively correlated with troponin T (r = 0.416, p < 0.01) and fibrinogen (r =
      0.560, p < 0.001), and IVST with hs-CRP level (r = 0.291, p < 0.05), whereas the
      EF was negatively correlated with hs-CRP (r = -0.301, p < 0.05). In addition, the
      high CRP group correlated positively with IVST (r = 0.281, p < 0.05), LVEDV (r =
      0.322, p < 0.05), and LVMI (r = 0.312, p < 0.05) and negatively with EF (r = 
      0.311, p < 0.05). On multivariate analysis, the high CRP group (beta = -0.312,
      beta = 0.238, and beta = 0.318, respectively) was a significant predictor of EF
      (R = 0.62, p = 0.025), LVMI (R = 0.928, p = 0.02) and IVST (R = 0.64, p = 0.01).
      CONCLUSIONS: Persistent elevation of CRP, which is an independent risk factor for
      EF, LVMI and IVST, may predict cardiac hypertrophy and dysfunction in patients
      maintained on hemodialysis.

PMID- 15863981
TI  - Clinical characteristics of stroke patients with antiphospholipid antibodies.
AB  - BACKGROUND: Antiphospholipid syndrome is important as a cause of ischemic stroke,
      although clinical characteristics of the syndrome are not well documented.
      METHODS: We analyzed differences in clinical characteristics between 40
      antiphospholipid-antibody (aPL)-positive and 40 aPL-negative stroke patients.
      RESULTS: Stroke patients with aPL were significantly younger and were more likely
      to be women in comparison with stroke patients without aPL. Valvular heart
      disease, neurological complications and hematological disorders were more
      frequent in the aPL-positive group. The mean value of thrombin-antithrombin III
      complex was significantly lower in the aPL-positive group. Cerebral infarctions
      in the carotid system were less and large-artery lesions more frequent in the aPL
      positive patients. CONCLUSIONS: Stroke patients with aPL have clinical
      characteristics distinct from stroke patients without aPL.

PMID- 15863982
TI  - Cerebral infarcts complicating tuberculous meningitis.
AB  - Cerebral infarction (CI) is a serious complication of tuberculous meningitis
      (TBM). It can be asymptomatic or symptomatic, causing stroke. We studied 40 TBM
      patients. All had initial CT brain scan, CT/MRI brain scan 3 months later and
      urgent CT brain scan for deterioration. CI was classified into lacunar infarction
      (LI) or large artery infarction (LAI). Twelve (30%) had CI, in 9 (23%) it was
      symptomatic and in 3 (8%) silent. Seven (58%) had LAI +/- LI. Eight (67%) had
      multiple CI. Two died from brainstem CI and 6 were dependent at 1 year. Patients
      with LAI might develop posterior circulation CI more frequently than those with
      LI only. CI is a common complication of TBM locally, with LAI and multiple CI
      being common. Two thirds of TBM patients complicated by CI had poor prognosis
      despite adjunctive dexamethasone treatment.

PMID- 15863983
TI  - Antifungal chemotherapeutics.
AB  - This review addresses trends in outcome and risk factors for invasive fungal
      infections, current antifungal agents and new therapeutic strategies. Current
      prospects for new therapies rest upon caspofungin, the first of a new class of
      antifungal molecules, the echinocandins, and new extended-spectrum azoles,
      voriconazole, posaconazole and ravuconazole. Approval by the Food and Drug
      Administration of the USA and the European Medicine Agency was given in 2001-2002
      to voriconazole and caspofungin. Voriconazole clearly demonstrated a decrease in
      mortality in invasive aspergillosis and fusariosis fungal infections.

PMID- 15863984
TI  - The prevalence of atrial fibrillation among acute medical admissions in Kuwait.
AB  - OBJECTIVE: To establish the prevalence of atrial fibrillation (AF) among acute
      medical admissions to the Adan Hospital, Kuwait, and to evaluate the clinical
      features of the patients. SUBJECTS AND METHODS: Of 2,833 acute medical admissions
      to the Adan Hospital from January 1 to May 31, 2003, 120 patients with AF were
      included in the study. The patients were divided into paroxysmal or persistent
      (PPAF), and chronic atrial fibrillation (CAF). The prevalence of stroke and
      clinical features of the CAF patients with and without strokes were studied. All
      the patients with AF underwent echocardiography to evaluate left ventricular
      ejection fraction (LVEF) and left atrial dimension (LAD). RESULTS: The prevalence
      of AF in the study period was 4.24%, of which 68.3% had CAF and 31.7% had PPAF.
      The prevalence of heart failure, ischemic heart disease, systemic hypertension,
      and diabetes mellitus was 27.5, 55.8, 65.8, and 53.3%, respectively. Patients
      with CAF were older and had a higher prevalence of heart failure compared to PPAF
      patients. Of the patients with CAF, 26.8% had at least one episode of stroke. The
      CAF patients had lower LVEF and larger LAD than PPAF patients. Stroke patients
      with CAF had lower LVEF and larger LAD as compared to those without stroke.
      CONCLUSION: Atrial fibrillation is a common admission diagnosis in our hospital.
      Patients with AF commonly suffer from heart failure, hypertension, diabetes
      mellitus, and ischemic heart disease. There was a high prevalence of stroke among
      CAF patients.

PMID- 15863985
TI  - HLA-DR binding prediction and experimental evaluation of T-cell epitopes of
      mycolyl transferase 85B (Ag85B), a major secreted antigen of Mycobacterium
      tuberculosis.
AB  - OBJECTIVE: To identify T-cell epitopes of Ag85B by analysis of its sequence for
      prediction to bind HLA-DR alleles and evaluate the predicted peptides for
      recognition by T cells in antigen-induced proliferation assays.
      MATERIALS/SUBJECTS AND METHODS: The complete sequence of Ag85B was analyzed for
      HLA-DR binding prediction to 51 HLA-DR alleles by using a virtual matrix-based
      prediction program (ProPred). Synthetic peptides covering the sequence of mature
      Ag85B were also analyzed for binding to HLA-DR alleles, and evaluated for
      recognition in antigen-induced proliferation assays with Ag85B-specific T-cell
      lines established from the peripheral blood mononuclear cells of 10 HLA-DR
      heterogeneous tuberculosis patients. RESULTS: The ProPred analysis of the full
      length Ag85B (325 aa), signal peptide (40 aa) and the mature protein (285 aa)
      predicted their binding to 100, 76 and 98% of the 51 HLA-DR alleles,
      respectively. The analysis of 31 synthetic peptides for binding to HLA-DR alleles
      showed that 4 of them could bind >50% HLA-DR alleles, and were considered
      promiscuous. Testing of Ag85B-specific T-cell lines with synthetic peptides
      showed that all of the T-cell lines responded to one or more peptides of Ag85B,
      and 9 of the 10 cell lines responded to one or more of the four peptides
      considered promiscuous for binding to HLA-DR alleles. CONCLUSION: The ProPred
      program was useful in predicting the HLA-DR alleles binding regions of Ag85B and
      identifying the promiscuous peptides recognized by T cells.

PMID- 15863986
TI  - Comparison of postoperative hepatic function between laparoscopic and open
      cholecystectomy.
AB  - OBJECTIVE: In this prospective study, we evaluated the effects of
      pneumoperitoneum on hepatic function during laparoscopic (LC) and open
      cholecystectomy (OC). SUBJECTS AND METHODS: One hundred patients who underwent LC
      (n = 50) or OC (n = 50) were included in the study. The groups were similar in
      age, sex, weight and height. Following liver function tests (total bilirubin;
      gamma-glutamyltransferase, GGT; alkaline phosphatase, ALP), aspartate
      aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase
      (LDH) were obtained preoperatively and at 24 and 48 h postoperatively. Similar
      anesthesiologic protocol was used for both LC and OC. During LC, the intra
      abdominal pressure was maintained within the conventional range of 12-14 mm Hg.
      RESULTS: Total bilirubin, ALP, GGT and LDH levels remained unchanged from
      baseline in both groups without significant difference between them. A higher
      number of patients had increased values of ALT (26/50 vs. 5/50) and AST (23/50
      vs. 6/50) in LC compared to OC group. Although the difference was statistically
      significant (p < 0.000 for ALT and p = 0.0004 for AST) the increased level
      decreased at 48 compared to 24 h. CONCLUSION: The results indicate that LC is
      associated with transient elevation of ALT and AST. The disturbances in the
      function of the liver after LC are self-limited and not associated with any
      morbidity in patients with a normal liver function.

PMID- 15863987
TI  - Thwaites' diagnostic scoring and the prediction of tuberculous meningitis.
AB  - OBJECTIVE: This study was conducted to investigate the applicability of Thwaites'
      diagnostic criteria in order to differentiate tuberculous from bacterial
      meningitis. MATERIAL AND METHODS: The study was done retrospectively in HIV
      negative patients (n = 126) with meningitis. Of the 126 patients, 103 had
      bacterial meningitis and 23 patients had tuberculous meningitis. The diagnosis
      was confirmed microbiologically in 59 and 12 patients with bacterial and
      tuberculous meningitis, respectively. The prediction of tuberculous meningitis
      was determined by Thwaites' diagnostic scoring using parameters such as age,
      history of illness, white blood cell count, total cerebrospinal fluid (CSF) white
      cell count and the percent of neutrophils in CSF. The diagnostic value of the
      model was assessed by calculating the area under the receiver operating
      characteristic (ROC) curves. RESULTS: The sensitivity and the specificity of
      Thwaites' diagnostic scoring were 95.6% (22/23) and 70.8% (73/103), respectively.
      In microbiologically proven cases the sensitivity and the specificity were 91.7%
      (11/12), 79.7% (57/59), respectively. The area under the ROC curve value for the
      diagnostic scoring was 0.92. CONCLUSIONS: Thwaites' diagnostic score was found to
      be helpful in differential diagnosis of tuberculous meningitis, however, the
      usefulness of diagnostic scoring should be validated in large series especially
      in patients with viral meningitis and low CSF glucose levels.

PMID- 15863988
TI  - Dual modality of 18F-fluorodeoxyglucose-positron emission tomography/computed
      tomography in patients with cervical carcinoma of unknown primary.
AB  - OBJECTIVE: To evaluate an optimized F-18-flurodeoxyglucose-positron emission
      tomography/computed tomography (FDG-PET/CT) acquisition protocol for head and
      neck cancer and assess the usefulness of combined FDG-PET/CT in locating unknown
      primary tumors in patients with biopsy-proven cervical lymph node metastases.
      SUBJECTS AND METHODS: Twenty-one patients with cervical lymph node metastases of
      unknown primary tumors underwent staging with FDG-PET/CT. The images of FDG-PET
      alone, CT alone, FDG-PET/CT read side by side and fused and FDG-PET/CT were
      evaluated separately by 2 physicians. Imaging results were correlated with either
      histology (n = 14) or clinical follow-up (n = 7). RESULTS: On the fused FDG
      PET/CT images, primary tumors were identified in 12 patients (57%); with FDG-PET
      alone and FDG-PET and CT read side by side 11 (52%) primary tumors were found
      while CT alone identified 5 (23%) primary tumors. CONCLUSION: Our data indicate
      that fused FDG-PET and CT images increased the sensitivity of detecting carcinoma
      of unknown primary (CUP) tumors compared to CT alone, but not to FDG-PET alone or
      FDG-PET and CT read side by side. Hence accurate fusion of functional and
      morphologic data by FDG-PET/CT is a promising imaging modality in the clinical
      workup of patients with cervical CUP tumors.

PMID- 15863989
TI  - Self-reported medication use among adolescents in Kuwait.
AB  - OBJECTIVE: The objectives of this study were to describe and examine the pattern
      of medication use, including age and gender differences among adolescents in
      Kuwait, and to establish the sources of information on medicines in this age
      group. SUBJECTS AND METHODS: A cross-sectional survey of 1,110 male and female
      students (14-21 years) from 10 randomly selected public schools in Kuwait was
      conducted. The prevalence of self-medication was estimated. RESULTS: The
      prevalence of self-medication among the high school students was 92%. The
      prevalence increased by age from 87% among 14-year-olds to 95% among 18-year
      olds. Sixty-five percent of medicines used were for pain relief, 54% for
      respiratory conditions, 39% for allergic conditions, and 37% for dermatological
      conditions. Twenty-two percent of medicines were nutritional supplements and
      vitamins, 21% gastrointestinal products, 17% antidandruff products, 15% hair
      products, 13% for migraine while 8% were for athlete's foot. Pain relief,
      respiratory, dermatologic and hair products were more prevalent in female
      adolescents than in male while antidandruff and athlete's foot preparations were
      used more by male adolescents. The most common sources of information on
      medicines were parents. CONCLUSION: The prevalence of self-medication among
      adolescents in Kuwait is high. Self-medication tended to increase with age and
      differed between male and female students. Few students consulted pharmacists for
      information on drugs. There is need to promote the image of the pharmacist in
      Kuwait as a provider of medication information.

PMID- 15863990
TI  - Evaluating diabetic foot infection with magnetic resonance imaging: Kuwait
      experience.
AB  - OBJECTIVE: The aim of this study was to evaluate the capability of magnetic
      resonance imaging (MRI) to depict and characterize the changes seen in diabetic
      foot infections. SUBJECTS AND METHODS: MRI studies of 29 diabetic patients with
      suspected foot infection were evaluated. Sagittal and transverse T1-weighted
      images before and after intravenous gadolinium, and transverse fat-suppressed T2
      weighted images were performed on the affected regions. The MRI findings were
      compared to subsequent clinical and/or histopathological findings. RESULTS: The
      MRI findings were: osteomyelitis in 14 patients, abscess in 5, cellulitis in 26,
      tenosynovitis in 4 and neuropathic joint in 8. Three cases were normal.
      Pathological confirmations were obtained in 19 patients. MRI and histological
      diagnosis were in concordance in 79% of osteomyelitis cases, 100% of neuropathy
      cases and 100% of cellulitis cases. The sensitivity and specificity of MRI in
      diagnosing osteomyelitis were 100 and 63%, respectively. The positive predictive
      and negative predictive values, and the accuracy were 79, 100 and 84%,
      respectively. MRI helped surgical planning for limb salvage procedures in 6 of
      the osteomyelitis cases and in a cellulitis case. CONCLUSION: The results
      indicate that MRI is a sensitive and accurate imaging modality for the evaluation
      of foot infections in diabetic patients and for planning proper treatment.

PMID- 15863991
TI  - Postmortem biopsies: the experience in Kuwait.
AB  - OBJECTIVE: To report our 4-year experience in postmortem needle biopsy of liver,
      heart, kidney and lung tissues when formal autopsy could not be performed.
      SUBJECTS AND METHODS: In the period from January 2000 to December 2003,
      postmortem biopsies were done at Al-Amiri Hospital, Kuwait, in 19 cases where the
      original diagnosis or cause of death was not clear. The procedure was performed
      by a dedicated trained medical team using a biopsy needle or limited incisions
      guided by the knowledge of the clinical presentation and results of laboratory
      and radiological investigations. RESULTS: The actual diagnosis was established in
      8 cases by postmortem histological findings and corrected in another 9 cases. In
      the remaining 2 cases with systemic sepsis, autopsy only confirmed the antemortem
      clinical diagnosis. CONCLUSION: Our study shows that needle biopsy is an adequate
      technique for postmortem examination and should be considered as the minimum
      alternative to conventional autopsy.

PMID- 15863992
TI  - The acute scrotum: a review of 40 cases.
AB  - OBJECTIVE: To determine the relative importance of clinical presentation,
      laboratory studies, and ultrasonography in the diagnosis of acute scrotum, and to
      suggest an effective method of management. SUBJECTS AND METHODS: Forty patients
      who were hospitalized between January 2002 and December 2002 for acute scrotum
      were studied with respect to history, physical examination, blood tests, urine
      analysis including culture, and scrotal ultrasonography with color Doppler study.
      RESULTS: Epididymitis (n = 24) was the commonest cause of acute scrotum followed
      by testicular torsion (n = 11), torsion of testicular appendages (n = 4), and
      idiopathic scrotal edema (n = 1). Both mean age (40.7 vs. 13.8 years), and
      average duration of pain at presentation (4.5 days vs. 19.1 h) were higher in
      patients with epididymitis than in torsion. Onset was usually insidious in
      epididymitis, sudden in testicular torsion, and variable in torsion of testicular
      appendages. The majority (87.5%) of patients with epididymitis were managed
      conservatively. The testis was salvaged in 81.8% of patients with testicular
      torsion. The accuracy of ultrasonography was only 72.7% in testicular torsion,
      but was good in epididymitis. CONCLUSION: Our results show that a careful
      clinical evaluation, by an experienced examiner, provides the correct diagnosis
      in acute scrotum rather than ultrasonography. It is of utmost importance to
      exclude testicular torsion in those who are younger than 16 years and whose pain
      duration is less than 24 h.

PMID- 15863993
TI  - Utilization of the pulmonary function test laboratory in the evaluation of
      respiratory disorders in the Al-Amiri Hospital: a secondary medical center.
AB  - OBJECTIVE: The aim of this study was to describe the current use of pulmonary
      function tests (PFT) and the degree of matching between the diagnoses at referral
      and after the test. SUBJECTS AND METHODS: A pre-test questionnaire was
      administered to 464 (5-88 years) patients referred to the PFT laboratory followed
      by a complete PFT test. The results of the patients' tests were analyzed in terms
      of the diagnosis before the test, its relation to symptoms, and the rate of
      concordance between the diagnoses before and after the test. RESULTS: The most
      referrals were from the medical Outpatient Department; 61%) and the most frequent
      diagnosis before the test was asthma (31.8%). Of the 464 patients, 34% were
      currently smoking cigarettes, and the most common symptoms were chronic dyspnea
      (30.2%) and chronic cough (19.6%). The chronicity of symptoms showed some
      association with the diagnosis before PFT in the case of chronic obstructive
      pulmonary disease (COPD) showing the symptom of dyspnea (p = 0.05), and COPD and
      restrictive lung disease with cough (p < 0.05). The overall rate of concordance
      in matching diagnoses before and after the test was 60.4% by consultant
      physicians and 51.9% by non-consultants, with an overall rate of 55% by all
      physicians. CONCLUSION: Our findings show that there should be better utilization
      of the PFT laboratory by physicians in all sub-specialities and there is a need
      to facilitate its use to make a better functional diagnosis.

PMID- 15863994
TI  - Reference ranges of lymphocyte subsets of healthy adults in Turkey.
AB  - The aim of this study was to determine the reference ranges of lymphocyte subsets
      in serologically HIV-negative healthy adults in Turkey. MATERIALS AND METHODS:
      Blood samples from 220 healthy adults, 105 female and 115 male, collected into
      tubes containing EDTA were investigated for lymphocyte subsets using flow
      cytometry. The age range was 18-80 years (44.80 +/- 16.69). RESULTS: The mean
      percentage and absolute values of the lymphocyte subsets were as follows: CD3:
      72.70 +/- 8.44%, 1,680 +/- 528 cells/microl; CD4: 47.37 +/- 9.10%, 1,095 +/- 391
      cells/microl; CD8: 28.99 +/- 5.99%, 669 +/- 239 cells/microl; CD19: 10.96 +/-
      4.44%, 254 +/- 122 cells/microl and CD56: 7.03 +/- 3.26%, 161 +/- 92
      cells/microl, respectively. The ratio of CD4/CD8 was 1.68 +/- 0.43. There was no
      statistically significant difference in the percentages and absolute values of
      lymphocyte subsets between the genders (p > 0.05). CONCLUSION: Immunophenotyping
      has been used to establish reference values of lymphocyte subsets in normal
      healthy adults in Turkey.

PMID- 15863995
TI  - Surgical management strategies in patients with primary hyperparathyroidism:
      which technique in which patients?
AB  - OBJECTIVE: This study was planned to investigate the efficacy of either 99mTc
      sestamibi scan or ultrasonography in predicting the operative treatment in
      patients with primary hyperparathyroidism (PHPT). SUBJECTS AND METHOD: Thirty
      patients (25 female, 5 male; mean age: 53 years) being operated for symptomatic
      primary PHPT were included in this study. Ultrasonography was used in 29 patients
      while 99mTc-sestamibi scintigraphy was done in 28 patients to localize the
      hyperfunctioning gland(s). Standard bilateral neck exploration was done in 6
      patients. Although unilateral intervention had been planned for 24 patients,
      bilateral intervention was performed in 9 of them. RESULTS: Sensitivity of 99mTc
      sestamibi was 81%, while that of ultrasonography was 42%. 99mTc-sestamibi
      localization method led to misleading results in 10/28 (35.7%) patients. False
      positive localization and accompanying thyroid pathologies played an important
      role in determining transition from unilateral to bilateral intervention.
      CONCLUSION: Our findings indicate that bilateral intervention remains a
      successful management option without prior localization in patients with PHPT
      especially in an endemic goiter region.

PMID- 15863996
TI  - Gelastic seizures in a young boy: evaluation by magnetic resonance imaging.
AB  - OBJECTIVE: To present an interesting case of gelastic seizures in a child who had
      an underlying brain lesion. CLINICAL PRESENTATION AND INTERVENTION: A 10-year-old
      boy presented with recurrent episodes of uncontrollable laughter since the age of
      6 years. Computed tomography showed a well-defined mass in the region of
      suprasellar and interpeduncular cisterns. Magnetic resonance imaging revealed a
      lesion, most likely a hamartoma, arising from the region of tuber cinerium. The
      lesion was subsequently resected and a marked improvement in the frequency and
      intensity of seizures was noted. CONCLUSION: This report shows that neuroimaging
      should be performed on patients with gelastic seizures to exclude any underlying
      structural lesion of causal significance.

PMID- 15863997
TI  - Acute transient cerebral toxicity associated with administration of high-dose
      methotrexate.
AB  - OBJECTIVE: To report the first case of transient central nervous system toxicity
      after administration of high-dose methotrexate (HDMTX) in the Middle East.
      CLINICAL PRESENTATION: A 10-year-old boy was diagnosed with osteosarcoma of the
      proximal end of the left tibia. He underwent primary amputation and was started
      on adjuvant chemotherapy, which included administration of HDMTX. He developed
      acute cerebral toxicity after the 5th dose of HDMTX in the form of diplopia,
      seizures and disorientation. He recovered completely without any complication or
      neurological sequelae. CONCLUSION: The acute cerebral toxicity associated with
      HDMTX was completely reversible and without any sequelae.

PMID- 15863998
TI  - Hodgkin's disease and autoimmune hemolytic anemia: a case report.
AB  - OBJECTIVE: To report a case of Hodgkin's disease presenting with immune hemolytic
      anemia. CLINICAL PRESENTATION AND INTERVENTION: A 47-year-old man was admitted to
      hospital because of weight loss, fever, and inguinal lymph node adenopathy.
      Biopsy of the inguinal lymph node revealed mixed-cellularity Hodgkin's disease.
      Three days after starting combined chemotherapy, the patient showed evidence of
      autoimmune hemolytic anemia, which responded well to prednisolone. CONCLUSION:
      This case shows that clinicians should be aware of the possibility of autoimmune
      hemolytic anemia in patients with Hodgkin's disease presenting with anemia, and
      distinguish it from the anemia of chronic disease.

PMID- 15863999
TI  - The need for routine antenatal HIV screening for pregnant women in Kuwait.

PMID- 15864000
TI  - Prediction of pancreatic cancer by serum biomarkers using surface-enhanced laser
      desorption/ionization-based decision tree classification.
AB  - OBJECTIVE: In order to improve the prognosis of pancreatic cancer patients, it is
      crucial to explore novel tools for its early diagnosis. Here, we attempted to
      screen serum biomarkers to distinguish pancreatic cancer from non-cancer
      individuals. METHODS: 47 serum samples from pancreatic cancer patients, 39 of
      whom had small surgically resectable cancers, were collected before surgery, and
      an additional 53 serum samples from age- and sex-matched individuals without
      cancer were used as controls. The surface-enhanced laser desorption/ionization
      (SELDI) ProteinChip was applied to analyze serum protein profiling. 54 samples
      (27 with pancreatic cancer and 27 controls) were analyzed in the training set by
      a decision tree algorithm to be able to separate pancreatic cancer from controls.
      A double-blind test was used to determine the sensitivity and specificity of the
      classification model. RESULTS: A panel of six biomarkers was selected to set up a
      decision tree as the classification model. The model separated effectively
      pancreatic cancer from control samples, achieving a sensitivity of 88.9% and a
      specificity of 74.1%. The double-blind test challenged the model with a
      sensitivity of 80% and a specificity of 84.6%. CONCLUSION: The SELDI ProteinChip
      combined with an artificial intelligence classification algorithm shows great
      potential for the diagnosis of pancreatic cancer.

PMID- 15864001
TI  - [Multiple endocrine neoplasia syndromes. Type 2].
AB  - The second type of multiple endocrine neoplasia syndromes can be described as
      rare syndromes, heritable in autosomal dominant manner and linking medullary
      thyroid carcinoma to different tumors of endocrine organ system and
      endocrinopathies. This syndrome is divided into multiple endocrine neoplasia
      syndrome type 2A (MEN 2A), characterized with combination of medullary thyroid
      carcinoma, pheochromocytoma and primary hyperparathyroidism; type 2B (MEN 2B),
      characterized with combination of medullary thyroid carcinoma, pheochromocytoma,
      marfanoid habitus and ganglioneuromatosis, and familial medullary thyroid
      carcinoma syndrome, characterized with the only indication, which is hereditary
      medullary thyroid carcinoma. Though type 2 multiple endocrine neoplasia syndrome
      has been known since 1961, yet, the cause of the syndrome, which is germline
      mutations of c-ret protooncogene, was detected just a decade ago and syndrome
      pathogenesis with its characterized endocrine neoplasia carcinogenesis machinery
      were detected. Implementation of progressive genetic researches in clinical
      practice enabled precise diagnosis of multiple endocrine neoplasia syndrome and
      its subtypes not only for ill patients but also for healthy syndrome inheritors,
      e.g. relatives of the sick. Stated genotype link to phenotype helps to
      prognosticate possible combinations of endocrine neoplasia and endocrinopathies,
      and to choose purposeful patient observation. Genetic screening of the inheritors
      of multiple endocrine neoplasia type 2 syndrome enabled purposeful researches and
      observations of patients with a huge risk of uprising endocrine neoplasia, it
      also enabled application of effective prophylaxis methods, avoidance or early
      diagnostic of malignant tumors and life prognosis improvement for patients with
      malignant tumors while practicing well-timed treatment adaptation. This
      literature review contains the newest data on multiple endocrine neoplasia
      syndrome type 2 and its pathogenesis, diagnostics, patient observation, endocrine
      cancer prophylaxis and methods of treatment, which are characteristic for
      syndrome and which are being chosen according to biochemical endocrine neoplasia
      symptoms and genetic diagnosis.

PMID- 15864002
TI  - [Prevention of intestinal ischemia after abdominal aortic reconstructive
      surgery].
AB  - The aim of this study was to estimate rate of intestinal ischemic complications
      after abdominal aortic reconstructive surgery, to evaluate risk factors and to
      provide means of prevention of complication. MATERIAL AND METHODS: Study group
      consisted of 172 patients who underwent aortic reconstruction in 2000-2003 in the
      Department of Vascular Surgery of Kaunas University of Medicine Hospital. Six
      patients underwent intestinal ischemia in the postoperative period, i. e. 3.5%;
      four of them died. This indicated that 13% of patients died after abdominal
      aortic surgery. Ninety-four patients underwent operation for aortoiliac occlusive
      disease, colon ischemia occurred in 1 case (1.1%). Seventy-eight patients
      underwent abdominal aortic aneurysm; 33 patients -- ruptured aneurysm, and 45 --
      aneurysm without rupture. In ruptured abdominal aortic aneurysm group with III
      degree colon ischemia there were 3 cases (9.1%); 2 of them died, which formed 11%
      of all deaths in this group. In the group of non-ruptured abdominal aortic
      aneurysm with III degree colon ischemia there were 2 cases (4.4%). Both patients
      died, which formed 50% of all deaths in this group. For all patients operated for
      abdominal aortic aneurysm, a. mesenterica inferior stump pressure was evaluated.
      In case of stump pressure 50 mmHg and more a. mesenterica inferior was ligated.
      If pressure was lower than 50 mmHg a. mesenterica inferior was reimplanted into
      vascular graft. Forty-nine reconstructions of a. mesenterica inferior were made
      in abdominal aortic aneurysm group: 25 in ruptured cases, and 24 in non-ruptured
      cases. Despite the fact that a. mesenterica inferior was reconstructed, 2
      patients had colon ischemia after this reconstruction in the group of ruptured
      aneurysm. In the group of non-ruptured aneurysm, colon ischemia developed only
      after ligation of a. mesenterica inferior. We conclude that a. mesenterica
      inferior is very important for normal circulation of left colon. Correct
      evaluation of preoperative aortography, correct operative strategy, and
      reimplanted a. mesenterica inferior if it is necessary -- are the main means of
      colon ischemia prevention after abdominal aortic surgery.

PMID- 15864003
TI  - Serum hormone levels and anthropometric characteristics in girls with
      hyperandrogenism.
AB  - Polycystic ovary syndrome is considered to originate during puberty. The aim of
      this study was to investigate hormonal status in relationship to anthropometric
      data in girls with premature adrenarche and adolescent girls with
      hyperandrogenism, as these conditions are related to polycystic ovary syndrome in
      adulthood. MATERIALS AND METHODS: 20 girls with premature adrenarche (aged 4.9
      10.2 years), 21 postmenarcheal girls with hirsutism (aged 13.3-17.8 years), 2
      groups (n=13 in each) of healthy volunteers of similar age and body mass index
      participated in the study. RESULTS: Serum testosterone and dehydroepiandrosterone
      sulphate levels were significantly higher in all patients than in controls. Free
      androgen index and leptin levels were significantly higher, and sex-hormone
      binding globulin lower in hirsute adolescents vs. controls. Birth weight standard
      deviation scores were comparable in all 4 groups. Serum dehydroepiandrosterone
      sulphate negatively correlated with birth weight standard deviation scores in the
      group of girls with premature adrenarche (r=-0.57, p<0.001). By linear
      regression, 76% in variation of serum leptin levels could be explained by
      subscapular skinfold thickness standard deviation scores, and by serum sex
      hormone-binding globulin, insulin, and dehydroepiandrosterone sulphate levels in
      all participants. Mean age of onset of menarche was younger in hirsute girls vs.
      controls (12.1+/-1.3 vs. 13.5+/-1.3 years, p=0.004). CONCLUSIONS: Inverse
      correlation of dehydroepiandrosterone sulphate levels and weight at birth
      indicates relationship between premature adrenarche in girls and fetal growth.
      Higher leptin levels in adolescents with hyperandrogenism than in healthy girls
      show possible involvement of leptin in pathogenesis of hyperandrogenism.

PMID- 15864004
TI  - [The diagnostic value of non-invasive tests for determining idiopathic dilated,
      ischemic and hypertensive cardiomyopathies].
AB  - The objectives of this study were to detect regional myocardial perfusion defects
      performing 99mTc-MIBI myocardial perfusion imaging and to compare the results
      with echocardiography for differential diagnostics of the idiopathic dilated,
      ischemic and hypertensive cardiomyopathies until coronary angiography will be
      performed. MATERIAL AND METHODS: In total 90 patients with cardiomegaly have been
      evaluated: 30 patients with idiopathic dilated cardiomyopathy (group I), 30 with
      ischemic cardiomyopathy (group II) and 30 with hypertensive cardiomyopathy (group
      III). All patients underwent 2D echocardiography examination and 99mTc-MIBI
      myocardial perfusion imaging before coronary angiography was done. RESULTS:
      Informative complex findings (age, thickness of the interventricular septum,
      thickness of the left ventricle posterior wall, the wall motion score index in
      the region of the right coronary artery and the left anterior descending branch
      and the degree of distress of myocardial perfusion in the area of right coronary
      artery circulation) selected by variable logic model enabled to differentiate
      patients with idiopathic dilated, ischemic and hypertensive cardiomyopathies with
      an accuracy of 92.0%, 86.2% and 79.2%, respectively. CONCLUSION: Informative
      echocardiographic indices (thickness of the interventricular septum and left
      ventricle posterior wall, the mass of the myocardium, the wall motion score index
      in the region of the right coronary artery and left anterior descending branch,
      ejection fraction) selected by discriminative analysis enabled to differentiate
      patients with idiopathic dilated, ischemic and hypertensive cardiomyopathies with
      an accuracy of 62.1%, 75.2% and 80.0%, respectively.

PMID- 15864005
TI  - [Influence of factors on occupational therapy efficiency for patients after
      stroke].
AB  - About 80% of patients become disabled after stroke due to cognitive, motor
      dysfunctions leading to unsatisfactory daily activity and efficiency. The aims of
      the research were to evaluate the level of biosocial dysfunctions of patients
      with stroke by functional independence measure (FIM) and to assess the
      effectiveness of occupational therapy and factors influencing it. The contingent
      of the examined patients consisted of 100 patients with stroke and rehabilitated
      in the Department of Neurorehabilitation of Kaunas University of Medicine
      Hospital. The findings of the research have shown that occupational therapy is
      effective to all patients. However, there were significant differences in the
      averages of FIM points (p<0.05) between low, medium and high effectiveness
      groups. The conclusion has been made that the effectiveness of occupational
      therapy is influenced by the following factors: the level of injury, the
      localization of brain damage, dysuria, passage, memory dysfunctions, unilateral
      neglect (p<0.05).

PMID- 15864006
TI  - Mitral valve prolapse: diagnosis, treatment and natural course.
AB  - This article analyzes data obtained from the medical records of the patients with
      primary mitral valve prolapse. The study population was the patients admitted to
      Kaunas University of Medicine Heart Center (KUMHC) between 1999 and 2003. The
      objective of our study was to analyze the natural course of mitral valve
      prolapse, complications and their frequency, treatment strategy in KUMHC, as well
      as to review the results of surgical treatment. We gathered data from the medical
      records of 160 patients and analyzed their age, medical history, complications,
      comorbidities, functional status and echocardiographic parameters. Patients who
      underwent mitral valve surgery were followed 7.9+/-8.4 months after procedure. On
      average, 32+/-14 patients with primary mitral valve prolapse were treated at
      KUMHC annually. Their mean age was 48.4+/-16.5 years, 44.4% of them were male.
      The most frequent complications of mitral valve prolapse were > or =II degrees
      mitral regurgitation (78.4%), various cardiac arrhythmias (68.1%) and heart
      failure of > or =II NYHA class (79%). Surgical treatment was recommended for 64
      (40%) KUMHC patients with primary mitral valve prolapse. Surgical treatment was
      applied in 44 (28.1%) of study patients. The patients, who were recommended
      surgical treatment, were older (mean age 53.2+/-11.9 years, p<0.05) and
      predominantly male (62.5%, p<0.05) as compared to medically managed patients. The
      heart failure (62.5% had NYHA class III or IV), severe mitral regurgitation
      (95.3% had mitral regurgitation of > or =III degrees ) and worse left ventricle
      function (15% had ejection fraction of <50%) were more frequent in this group as
      compared to medically managed patients (all p<0.05). During the last five years
      the number of hospitalized patients with primary mitral valve prolapse increased
      3.2 times, the number of mitral valve surgical procedures among these patients
      increased 2.8 times, and the number of mitral valve repair increased 15.8 times.
      56.8% of patients had uncomplicated postoperative course. The most frequent
      postoperative complication was new arrhythmias and/or conduction disturbances. 1
      patient died in early postoperative period. There was significant decrease in
      left ventricle and left atrium size and the severity of mitral regurgitation 2 to
      6 months after mitral valve surgery. These positive changes remained during all
      study period. Taking in the consideration the large number of mitral valve repair
      procedures and good outcomes, the low postoperative mortality of the surgical
      mitral valve prolapse treatment in KUMHC, we can strongly recommend surgical
      treatment for the patients with severe mitral regurgitation secondary to mitral
      valve prolapse.

PMID- 15864007
TI  - [Carotid artery atherosclerotic stenosis, plaque structure and stroke].
AB  - OBJECTIVES: The main indication for carotid endarterectomy is severity of
      stenosis carotid artery. Several studies have shown the relationship between
      carotid plaque morphology and cerebrovascular disorders. The purpose of this
      study was to evaluate the structure of carotid plaque and correlate carotid
      plague morphology with neurological symptoms, stroke risk factors, severity of
      carotid stenosis and operative stroke. METHODS: Operative specimens of 262
      carotid plaques were examined macroscopically. Plague morphology was
      characterized as either heterogeneous or homogeneous. Stroke risk factors,
      cerebrovascular symptoms, severity of carotid stenosis and risk for mortality and
      operative stroke were compared between symptomatic and asymptomatic patients with
      heterogeneous and homogeneous plague. RESULTS: Heterogeneous plaques were present
      in 198 (75%) of 262 arteries. Heterogeneous plaques were found in 121 symptomatic
      and 77 asymptomatic patients (p<0.001). Homogeneous plagues did not differ in
      symptomatic and asymptomatic patients. The structure of plaque did not correlate
      with any severity of stenosis. There were no significant differences in age, sex,
      smoking and arterial hypertension between heterogeneous and homogeneous groups.
      Higher level of fibrinogen but not hypercholesterolemia was associated with
      heterogeneity of plaque. Postoperative stroke was mainly present in the patients
      with heterogeneous plaques, but the difference was not statistically significant.
      CONCLUSIONS: Heterogeneous plaques were present in 75 % of patients with carotid
      artery stenosis. Heterogeneous plagues were associated with cerebrovascular
      symptoms more often than homogeneous ones. Plague structure did not correlate
      with severity of carotid artery stenosis and operative stroke was not associated
      with plaque heterogeneity. These findings suggest that plague heterogeneity
      should be considered in selecting patients for carotid endarterectomy.

PMID- 15864008
TI  - Helicobacter pylori substantially increases oxidative stress in indomethacin
      exposed rat gastric mucosa.
AB  - Helicobacter pylori (H. pylori) often play an important role in the pathogenesis
      of gastritis, peptic ulcer, and probably also gastric cancer. Reactive oxygen
      species (ROS) produced by this bacterium may be one of the crucial factors
      whereby oxidative stress can play a role in the pathogenesis of ulcer disease.
      The aim of this study was to assess ROS activity and glutathione redox status, a
      principal cellular redox sensor, in H. pylori-associated indomethacin-induced
      gastric ulcers in rats. Gastric lesion was produced by intragastric
      administration of indomethacin (7 mg/kg) for three days followed by
      administration of H. pylori suspension (density 10(9) colony forming units).
      Animals receiving indomethacin only or followed by administration of H. pylori
      suspension were sacrificed after 11 and 18 days. ROS activity was assessed by the
      level of lipid peroxidation (LPO) and the glutathione redox status by the ratio
      between oxidized and reduced glutathione (GSSG/GSH). Indomethacin did not
      significantly increase the level of LPO and the GSSG/GSH ratio. When H. pylori
      suspension was given together with indomethacin the LPO was increased both on
      days 11 and 18 and GSSG/GSH on day 18. H. pylori, thus, substantially increases
      glutathione redox ratio and lipid peroxidation in gastric mucosa, which may play
      an important role in the pathological mechanisms of this bacterium. The findings
      support the idea that dietary antioxidants could be beneficial in combination
      therapy for eradication of H. pylori.

PMID- 15864009
TI  - [Passive smoking and respiratory health of children].
AB  - Passive smoking has been shown to be a risk factor for respiratory diseases in
      children. Some authors reported reduced lung function of children exposed to
      passive smoking. The purpose of the study was to assess the prevalence of
      exposure to passive smoking and its relation to respiratory health of Kaunas
      children. In 1998-2000 a cross-sectional survey was conducted in 20 kindergartens
      of Kaunas. Survey participants were 594 children (356 boys and 238 girls) aged 6
      7 years. Children's parents filled out a questionnaire of the Swiss Study on
      Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution designed
      on the basis of International Study of Asthma and Allergy in Childhood. Exposure
      to passive smoking was determined by an answer "everyday" or "sometimes" to the
      question "How often is your child in surrounding where someone smokes?". The
      parameters of respiratory function (FVC, FEV1, FEV1/FVC, FEF25, FEF50, FEF75,
      PEF) were measured with Pony Graphics 3.5. Response rate was 58.6% to 69.2%
      depending on a kindergarten. More than two fifth of children were exposed to
      passive smoking at home. Cough that lasted for at least four weeks during the
      past year was experienced by 24.5% and 16.9% of children with and without
      exposure to passive smoking (p<0.05). Wheezing in the past was found in 43% and
      27% of children in groups compared (p<0.05). There was a significant difference
      in prevalence of sneezing or a runny/blocked nose when a child did not have a
      cold among children with and without exposure to passive smoking (46.6% and
      36.6%, respectively, p<0.05). FEF25, FEF50, FEF75 and PEF of exposed girls were
      significantly lower than that of girls not exposed to passive smoking. Multiple
      regression analysis that included variables such as passive smoking, family
      history of allergy, smoked mother during pregnancy, gas stove and pets in child's
      room showed that FEF25 and FEF50 in girls were related to passive smoking. Our
      data show that more than two fifth of children are exposed to passive smoking
      which is associated with increased prevalence of chronic cough, wheezing, running
      nose and sneezing without cold. Passive smoking is also related to decreased lung
      function, especially for small airway flows.

PMID- 15864010
TI  - [Health resorts and development of the health resort medicine in Lithuania].
AB  - Lithuanian health resorts are national resources of this country. Body hardening,
      health promotion, disease prevention and rehabilitation by means of applying
      natural factors are linked for centuries with the names of health resorts such as
      Druskininkai and Birstonas. The effect of natural factors is multiplex and
      depends on many parameters the study of which in concrete health resorts is
      indispensable in order to individualize the treatment at the health resorts and
      avoid undesirable side effects. As the contingent of the patients being referred
      to the sanatoria is changing--the number of severe patients after acute disorders
      and traumas is increasing constantly--the need of such studies becomes relevant.
      However, after renewal of independence of Lithuania in 1990, the policy of health
      resort development on the national scale has not been carried out yet. Besides,
      the number of localities that aim for becoming health resorts is increasing,
      however, such localities often do not meet the required criteria. The article
      reviews the status of health resorts and their localities together with their
      regulations in Lithuania, their development, specificity, the effects of the
      health resort natural factors (climatotherapy, balneotherapy, pelotherapy) on the
      healthy body and patients. The data are presented on the development of research
      studies concerning health resorts and main trends of health resort medicine:
      health promotion, prevention of disorders, early health resort rehabilitation,
      health resort tourism, treatment and health resort etiology. Possibilities of
      revival of studies concerning the effects of health resort factors on the
      rehabilities are discussed.

PMID- 15864011
TI  - [Hemospermia].
AB  - Hemospermia refers to the presence of blood in the seminal fluid and is not very
      common urologic symptom. Its prevalence remains unknown. Historically,
      hemospermia was linked to excessive sexual overindulgence, prolonged sexual
      abstinence, interrupted coitus. Newer imaging modalities have altered the
      diagnosis and etiological factors of hemospermia are now more frequently
      identified. Hemospermia can result from many causes. Infections or inflammatory
      disorders account from 39% to 55% of cases, malignancies and trauma account just
      4-13%. The remaining 11% of cases were caused by a variety of other pathologic
      conditions. Predisposing diseases are prostatitis, epididymitis, urinary stones,
      tuberculosis, cirrhosis of the liver, arterial hypertension, hematologic
      diseases. In 30-70% of the cases there is no association with any significant
      pathology. Cases of primary and solitary hemospermia can be adequately assessed
      by urinanalysis, blood pressure measurement, genital and rectal examination, PSA
      test, and reassurance of the patient. Persistent and recurrent cases of
      hemospermia are best clarified by transrectal ultrasound examination, cystoscopy,
      computer tomography and magnetic resonance imaging. Treatment depends on the
      diagnostic findings but often simply involves reassurance.

PMID- 15864012
TI  - Imbalance of matrix metalloproteinase-9 and tissue inhibitor of matrix
      metalloproteinase-1 is associated with pulmonary emphysema in Klotho mice.
AB  - Klotho mice, which exhibit multiple phenotypes resembling human aging, develop
      pulmonary emphysema. In this study, to clarify the mechanism of their
      emphysematous change through development, we evaluated the expression of matrix
      metalloproteinase (MMP)-2, 9 and the tissue inhibitors of matrix
      metalloproteinase (TIMP)-1, 2 in the lungs of Klotho mice and wild type mice.
      Klotho mice showed obvious air space enlargement at 5 weeks of age, but not at 2
      weeks of age. Immunohistochemical analysis revealed that expression of MMP-9 was
      increased in Klotho mice compared with wild type at 5 weeks of age. Western blot
      analysis and gelatin zymography also revealed that the expression and the
      gelatinolytic activity of MMP-9 were increased in the lungs of Klotho mice. The
      expression of TIMP-1 decreased in the lungs of Klotho mice. MMP-2 and TIMP-2
      showed no significant differences at 5 weeks of age. At 2 weeks of age, there
      were no significant differences in the expressions of MMP-9 and TIMP-1 between
      Klotho and wild type mice. These findings suggest that imbalance of MMP-9 and
      TIMP-1 is associated with the development of pulmonary emphysema in Klotho mice.

PMID- 15864013
TI  - T-138C polymorphism of matrix gla protein promoter alters its expression but is
      not directly associated with atherosclerotic vascular calcification.
AB  - Matrix Gla protein (MGP) is a crucial inhibitor of vessel and cartilage
      calcification. We investigated the association of T-138C MGP promoter
      polymorphism with the degree of atherosclerosis, vascular calcification and
      patients' clinical background including calcification of the trachea and costal
      cartilage. Analysis of 108 autopsy cases was carried out by polymorphism-specific
      PCR on formalin-fixed paraffin-embedded samples. Statistical correlations among
      eight risk factors and five markers related to atherosclerosis and extra-bone
      tissue calcification were multivariantly analyzed. We found very high canonical
      correlations between the factors and the markers, and Pearson's correlation
      analysis revealed six significant correlations between age and the Gore index;
      age and costal cartilage calcification; sex and costal cartilage calcification;
      hypertension and the Gore index; hypertension and the calcification factor of the
      Gore index; and hyperlipidemia and costal cartilage calcification. The promoter
      activity of the -138T allele was significantly higher than that of the -138C
      allele; treatment with 12-O-tetradecanonylphorbol 13-acetate (TPA) significantly
      activated the former, but had almost no effect on the latter. The C genotype was
      significantly common among Japanese subjects, (TT 45.5%, TC 37.6% and CC 16.8%)
      compared with that reported in the Netherlands, Northern Ireland and France. No
      significant correlation was observed, however, between T-138C MGP promoter
      polymorphism and the markers. Although the C genotype (TC+CC) tended to show a
      higher calcification factor than the TT genotype, no significant difference was
      observed among the genotypes in the Gore index or in the calcification factor.
      Although MGP promoter activity and the binding of the AP-1 transcription factor
      were clearly different between T-138 and C-138 MGP promoter polymorphism in
      vitro, T-138C polymorphism was, statistically, not an independent factor of
      atherosclerosis or atherosclerotic vascular calcification in the abdominal aorta.

PMID- 15864014
TI  - Augmentation of third generation instrumentation with sublaminar titanium wiring
      in late onset idiopathic scoliosis: the surgical results and analysis of trunk
      balance.
AB  - In recent years, third generation instrumentation systems which achieve
      correction by maneuvers like derotation and translation, have been widely used in
      the treatment of idiopathic scoliosis. To increase correction, additional
      procedures that increase stability, such as screw application for every segment,
      have been used. In this study, as a new technique, the effects of combined
      translation and derotation maneuver with augmentation by using titanium double
      crimp Songer cable applied on apical region, on trunk balance, sagittal and
      frontal planes have been examined. 45 idiopathic scoliosis patients operated
      between 1996 and 2002 have been included in the study. Mean age was 14.5+/-1.7
      years and female/male ratio was 30/15. Mean follow up time was 51.9+/-22.7
      months. According to King Classification, 15 patients had Type II, 18 patients
      Type III and 12 patients had Type IV curves. One of the apical cables has been
      tensioned and translation has been performed. At the second step, derotation has
      been applied to the vertebra, which is firmly attached to the rod. Sagittal and
      frontal Cobb angles have been measured in preoperative, postoperative and recent
      radiographic examinations. Trunk balance has been examined both clinically and
      radiographically. Also, secondary curves have been measured in every examination
      for decompensation findings. In overall frontal plane measurements, postoperative
      correction was 79.9+/-13.5 %, loss of correction 2.9 degrees +/-3.2 degrees and
      final correction 74.3 % +/-14.3 %. In postoperative measurements, normal
      physiological contours have been achieved in 97.8 % of the patients for the
      thoracic region (30 degrees -50 degrees ) and 80.7 % of the patients for the
      lumbar region (40 degrees -60 degrees ). In secondary curves, 75.2+/-34.4 %
      postoperative correction has been observed. No decompensation findings have been
      observed in the last examination. In postoperative and last follow up
      examinations, balanced and totally balanced vertebral column has been achieved in
      every patient of the study group. Solid fusion mass has been observed in every
      patient. No early or late, local or systemic postoperative complications have
      been observed. Given these findings, we conclude that derotation-translation
      combined maneuver performed with 3rd generation instrumentation reinforced
      sublaminar wires is a good choice in the treatment of the late-onset idiopathic
      scoliosis.

PMID- 15864016
TI  - [Recent progress of mast cell research].

PMID- 15864017
TI  - [Allergic inflammation and eosinophils: trials, tribulations and enigma of IL-5,
      eosinophils and asthma].

PMID- 15864018
TI  - [IL-17/IL-18 and allergy].

PMID- 15864019
TI  - [Clinical analysis of allergic rhinitis (pollinosis) in Hokkaido].
AB  - We investigated the positive rate of specific IgE to various allergens in 548
      patients with allergic rhinitis who visited 13 hospitals in Hokkaido in 2001.
      House dust and mite were most common allergen in our study. On the other hand,
      the positive rate for pollens were in the order of birch, timothy, orchard grass,
      and mugwort. In comparison with past study, the positive rate to birch had
      increased and the positive rate to timothy and orchard grass had decreased. The
      positive rate of specific IgE to birch was higher in Asahikawa, its neighborhood,
      and Sapporo, while Kushiro, Tomakomai, Wakkanai, and Nemuro lie on the coast were
      lower region. These findings suggested that the positive rate of specific IgE to
      birch varies in different region even in the same island, Hokkaido and might be
      influenced by climate.

PMID- 15864020
TI  - [Examination of effectiveness of olopatadine hydrochloride in atopic dermatitis].
AB  - Subjective/objective symptoms (itching, papula, erythema, lichenification,
      desquamation, scratching, erosion) and the levels of IgE, LDH, interleukin (IL) 
      6, thymus and activation-regulated chemokine (TARC) were compared before and
      after administering olopatadine hydrochloride (ALLELOCK tablets) to 17 atopic
      dermatitis (AD) patients. Subject/objective symptoms improved significantly after
      administering the agent, and the total dosage of the combined topical steroids
      was also significantly decreased after administration (p<0.05), although IgE, IL
      6 and LDH levels did not change, TARC was significantly decreased (p<0.05). The
      correlation between the levels of IgE, IL-6, LDH and TARC before and after the
      administration was examined. There was a positive correlation between IgE and
      TARC (r=0.62, p<0.01) and between IL-6 and TARC (r=0.78, p<0.01). Olopatadine
      hydrochloride is therefore useful in improving the symptoms in AD, and TARC may
      be used as an indicator of the symptom improvement.

PMID- 15864021
TI  - [A case of systemic lupus erythematosus presenting with jaundice and lupus
      pneumonia].
AB  - A 27-year-old Japanese woman was referred to our hospital for acute hepatitis in
      April 2002. She had been suffering from low grade fever and fatigue for a week.
      She also presented with dyspnea. On admission, ALT and AST were 857 U/l and 473
      U/l respectively. Urine protein was 2 g/day. Chest radiograph showed bilateral
      infiltrative shadow and pleural effusion. She developed jaundice and her level of
      total bilirubin was increased to 9.6 mg/dl on May 9. Antibodies to hepatitis
      viruses were not detected. Testing for antimitochondrial antibodies, antismooth
      muscle antibodies, and antiribosomal P antibodies showed all negative. However,
      antinuclear antibodies were positive at titer 1:160 and anti-double stranded DNA
      antibodies were 130 U/ml. A diagnosis of systemic lupus erythematosus was made
      and oral administration of 60 mg/day prednisolon was started on May 10. Serum
      levels of ALT, AST and bilirubin were reduced to within normal range and
      pulmonary lesions were also improved. We conclude that this is a rare case of
      systemic lupus erythematosus presenting with acute hepatitis and jaundice.

PMID- 15864022
TI  - Physician ownership in specialty heart hospitals: successful and under siege.

PMID- 15864023
TI  - Dollars and stents: the economics of drug-eluting stents.
AB  - By averting restenoses, drug-eluting stents (DES) reduce the need for repeat
      revascularization procedures and improve quality of life. Large, randomized
      clinical trials including the Sirolimus-Eluting Balloon Expandable Stent in
      Treatment of Patients With De Novo Native Coronary Artery Lesions (SIRIUS)
      suggest that DES may be cost-effective to the Medicare system over time. However,
      the high cost of DES and the loss of revenues from revascularization procedures
      coupled with inadequate Medicare reimbursement are likely to have adverse effects
      on hospitals, making it hard to meet their bottom line. Key contributors to this
      problem include the unequal distribution of Medicare reimbursement based on
      diagnosis-related groups or diagnosis-related group calculations and the lack of
      price competition for DES. The economic burden of restenoses, the efficacy of DES
      in averting restenoses, the cost-effectiveness of DES, and the interaction of
      Medicare, DES manufacturers, and hospitals are reviewed. Using specific cost
      containment strategies, hospitals can better maneuver the financial barriers to
      optimize DES utilization.

PMID- 15864024
TI  - Tribute to Dr. G. Dean MacEwen.

PMID- 15864025
TI  - Evaluation of kidney anomalies in congenital scoliosis. 1972.

PMID- 15864026
TI  - Prenatal diagnosis of musculoskeletal anomalies.
AB  - Musculoskeletal anomalies are not uncommon in prenatal life. They can be either
      sporadic or part of chromosomal syndromes causing prenatal morbidity and
      mortality. The prenatal diagnosis of musculoskeletal anomalies is based on
      information assembled from various imaging modalities and from biochemical and
      genetic workups. The prenatal diagnosis can serve as a prognostic tool and in
      counseling the parents. Among the imaging methods, ultrasonography is the most
      popular and cost effective in observing and following fetal development from the
      very early stages of gestation. Transvaginal sonography can detect and identify
      most of the normal and the specific pathologic changes very close to the stage of
      their embryogenic development. From a practical point of view, early detailed
      transvaginal sonography screening at 14 to 15 weeks of gestation is very useful
      while late detection at 20 to 23 weeks of gestation may provide some additional
      information in low-risk pregnancies. Very early screening, even during the ninth
      week, may be indicated in high-risk pregnancies. Additional genetic counseling is
      recommended when abnormal findings are suspected. We summarize the diagnostic
      approach and the information available for the most common musculoskeletal
      anomalies.

PMID- 15864027
TI  - Polydactyly, triphalangism of the thumb, and carpal abnormalities in a family.
AB  - Many authors have documented the anatomic variability of radial-sided polydactyly
      and triphalangism of the thumb, but the relationship between these two conditions
      remains confusing. This study was done to determine if all types of radial-sided
      polydactyly and triphalangism of the thumb are related. Twenty-five members of a
      family with these abnormalities were evaluated clinically and radiographically by
      using radiographs of the hands and feet and, where appropriate, the tibia, in
      order to ascertain whether all variations of radial-sided polydactyly and
      triphalangism of the thumb could be found in this family. The hand abnormalities
      comprised eight types based on the number of digits, the number of phalanges, and
      whether the digits or phalanges were normal, hypoplastic, or rudimentary. Five
      distinct carpal anomalies were identified. Essentially all described types of
      radial-sided polydactyly and triphalangism of the thumb occur in this family. The
      occurrence of these abnormalities is determined by a single autosomal dominant
      gene. The manner in which the gene is expressed is determined either by its
      allele or by a combination of genetic and environmental factors. The findings in
      the parent cannot be used to predict the findings in the offspring.

PMID- 15864028
TI  - Congenital vertical talus in arthrogryposis and other contractural syndromes.
AB  - No practical classification system exists to identify which patients may have
      successful outcome following treatment of congenital vertical talus in
      arthrogryposis. We classified 229 patients into five distinct groups: Group I had
      amyoplasia or so-called classic arthrogryposis, Group II had distal
      arthrogryposis, Group III had a specific syndrome as a diagnosis, Group IV had
      severe systemic or neurologic involvement, and Group V had unclassifiable
      contracture syndromes. No patient with amyoplasia (Group I) had congenital
      vertical talus. The congenital vertical talus seen in distal arthrogryposis
      (Group II) was milder than that seen in Groups III or IV and feet in this group
      responded well to early one-stage surgical correction. Congenital vertical talus
      that occurred in association with a generalized syndrome or with extensive
      systemic and neurologic involvement (Groups III and IV) was severe and refractory
      to treatment. Most children in these groups were unable to walk; therefore, the
      goal of treatment should be to achieve a pain-free foot to allow fitting of
      normal shoes. Most children in Group V were able to walk and responded well to
      operative correction; they should be treated before walking age.

PMID- 15864029
TI  - Infant and child motor development.
AB  - Identifying infant and child developmental delay is a skill important for
      orthopaedic surgeons to master because they often are asked to distinguish
      between normal and abnormal movement. An emphasis has been placed on early
      detection and referral for intervention, which has been shown to enhance the
      lives of the infant or child and his or her family. Appropriate recognition of
      delay is necessary for referral to early intervention services, which serve to
      help these children overcome or improve motor dysfunction and to help families
      grow more confident in caring for children with special needs. We define early
      intervention, discuss normal and abnormal motor development, and provide useful
      examination tools to assess motor development.

PMID- 15864030
TI  - Selective screening for scoliosis.
AB  - Scoliosis screening has been practiced for nearly 50 years and has provided
      valuable knowledge about the prevalence and natural history of scoliosis. Early
      diagnosis allows for nonoperative treatment, like wearing an orthosis that has
      been shown to be effective by numerous outcome studies. Challenges in scoliosis
      screening include the low prevalence rate of clinically significant scoliosis,
      the inverse relationship of sensitivity and specificity in the screening process
      because of the poor correlation of clinical deformity and radiographic
      abnormality, and the inflated cost of these programs because of overreferral.
      Recommendations for improvement include redefinition of what actually constitutes
      a "significant" scoliosis for screening, diagnostic, and outcome purposes;
      selective screening of only immature females; the use of objective referral
      criteria; and re-screening patients rather than referring those who have
      borderline cases.

PMID- 15864031
TI  - Spondylolysis and spondylolisthesis in the child and adolescent: a new
      classification.
AB  - Spondylolysis and spondylolisthesis commonly are diagnosed in children and
      adolescents. The diagnostic workup and treatment plan vary widely among
      physicians. Although the orthopaedic literature is extensive on the topic, it is
      our opinion that a lack of clarity exists with regards to etiology, terminology,
      subtypes of spondylolysis and spondylolisthesis, and treatment. Important basic
      principles regarding spondylolysis and spondylolisthesis, with emphasis on
      clinical evaluation and nonsurgical treatment, serve as the basis for a new
      classification. We propose a new classification for pediatric spondylolysis and
      spondylolisthesis that is comprehensive, simple, and easily applied. This scheme
      is based on clinical presentation and spinal morphology and is more appropriate
      for the child and adolescent than the existing classification schemes of Wiltse
      Newman and Marchetti-Bartolozzi. Algorithms for evaluation and treatment of
      spondylolysis and spondylolisthesis in children and adolescents, based on this
      new classification, are presented.

PMID- 15864032
TI  - Vertebral body stapling procedure for the treatment of scoliosis in the growing
      child.
AB  - Thirty-nine consecutive patients have had vertebral body stapling of 52 curves
      (26 patients with one curve stapled and 13 with two). For the group with patients
      who were 8 years or older with less than 50 degrees preoperative curve and a
      minimum 1-year followup, coronal curve stability was 87% when defined by
      progression less than or equal to 10 degrees . Fusion was necessary in two
      patients. No curves less than 30 degrees at the time of stapling progressed
      greater than or equal to 10 degrees . Major complications occurred in one patient
      (2.6%, diaphragmatic hernia) and minor complications occurred in five patients
      (13%). Further followup of the patient cohort and further research into efficacy
      and indications are warranted.

PMID- 15864033
TI  - Video-assisted thoracoscopic surgery: the Cincinnati experience.
AB  - Video-assisted thoracoscopic surgery is an alternative to open thoracotomy. We
      analyzed our experience during a consecutive series of 100 patients who had this
      procedure and who were available for study at 3-year followup. Video-assisted
      thoracoscopic surgery was done on patients with the following diagnoses:
      idiopathic scoliosis (n = 49), neuromuscular spinal deformity (n = 15),
      Scheuermann kyphosis (n = 15), congenital and infantile scoliosis (n = 5),
      neurofibromatosis (n = 5), Marfan (n = 1), postradiation scoliosis (n = 1), and
      repair of pseudoarthrosis (n = 1). Four patients had excision of the first rib to
      treat thoracic outlet syndrome. One patient had excision of an intrathoracic
      neurofibroma and one a benign rib tumor. One had anterior arthrodesis after
      fracture-dislocation of the thoracic spine and another had anterior fusion for
      vertebral osteomyelitis. The average operative time for the thoracoscopic
      anterior release with discectomy and arthrodesis was 253 minutes. The average
      number of discs excised was 8. Final postoperative scoliosis and kyphosis
      corrections were 68% and 90%, respectively. Complications related to thoracoscopy
      occurred in eight patients. Video-assisted thoracoscopic surgery provides a safe
      and effective alternative to open thoracotomy in the treatment of thoracic
      pediatric spinal deformities.

PMID- 15864034
TI  - Imaging methods used for children with hip dysplasia.
AB  - Ultrasound has been used to examine the infant hip for more than 20 years. The
      Thornbury model for assessing the clinical efficacy of a diagnostic imaging
      procedure has been used in this review to determine what has been achieved and
      what remains to be learned. To accomplish the effective and efficient treatment
      of patients with developmental dysplasia of the hip, orthopaedic, radiologic, and
      pediatric organizations must collaborate in writing and revising standards of
      care and guidelines for treatment as our knowledge base grows.

PMID- 15864035
TI  - A new modified technique of triple osteotomy of the innominate bone for
      acetabular dysplasia.
AB  - A new modified technique of triple osteotomy of the innominate bone has been
      devised and implemented for the treatment of residual acetabular dysplasia in
      children with developmental dysplasia of the hip. The procedure is done through a
      two-incision approach. The ischium, pubis, and iliac bones are osteotomized, with
      resection of a triangular wedge of bone from the outer cortex of the proximal
      part of the ilium. The resection of the triangular wedge of bone from the outer
      cortex alone creates a slot with the intact inner cortex serving as a stabilizing
      abutment where the distal posterior aspect of the ilium fits. This osteotomy
      allows for extensive coverage of the femoral head with greater stability. The
      stable construct of the osteotomy and pelvic fixation facilitates early weight
      bearing and obviates the need for hip spica cast immobilization. Since its
      conception the new triple osteotomy has been done in 11 children (13 hips). The
      preoperative vertical center edge angle of Weiberg was 8.9 degrees (range, 5
      degrees -17 degrees ). The postoperative vertical center edge angle was a mean of
      45.6 degrees (range, 31 degrees -58 degrees ). The last followup vertical center
      edge angle was a mean of 44.9 degrees (range, 29 degrees -58 degrees ). The mean
      preoperative acetabular angle of Sharp was 53 degrees (range, 48 degrees -61
      degrees ). The postoperative acetabular angle was a mean of 25.4 degrees (range,
      19 degrees -40 degrees ). The last followup acetabular angle was a mean of 28
      degrees (range, 18 degrees -41 degrees ). All patients went on to have bony
      unions on their innominate bone. We describe the technique for the osteotomy and
      presents preliminary results of all patients who had the procedure.

PMID- 15864036
TI  - Operative treatment for type II avascular necrosis in developmental dysplasia of
      the hip.
AB  - Lateral growth disturbance of the proximal femur may occur after treatment of
      developmental dysplasia of the hip, although usually it is not recognized until
      the child is older. This resultant dysplasia is also known as Kalamchi and
      MacEwen Type II avascular necrosis. The valgus configuration of the proximal
      femur and associated acetabular dysplasia may need operative reconstruction. Our
      purpose in doing this study was to assess the results of reconstruction in these
      patients. We reviewed 24 patients (30 hips) with Type II avascular necrosis who
      had acetabular and/or proximal femoral osteotomy after treatment for
      developmental dysplasia of the hip. The results were assessed according to the
      timing and type of operation and were graded using the Severin classification (I
      and II satisfactory and III and IV unsatisfactory). All patients were followed up
      past skeletal maturity. At a mean followup of 22 years, 15 of 24 patients (17 of
      30 hips) had a satisfactory result. The patients with hips that were
      reconstructed after the diagnosis of Type II avascular necrosis had more
      satisfactory results than those operated on before the diagnosis of (70% versus
      50%) avascular necrosis. Patients with 10 of the 13 hips that had acetabular and
      femoral reconstruction had a satisfactory result.

PMID- 15864037
TI  - Greater trochanteric transfer for the treatment of coxa brevis.
AB  - We reviewed the outcomes of 28 patients for whom we did greater trochanteric
      transfer. Twenty-two (79%) patients treated for coxa brevis by greater
      trochanteric transfer had good relief of pain and limp. Four (1%) outcomes were
      fair and two (0.7%) were poor. Our outcomes compared favorably with those already
      reported in the literature. Patients who had avascular necrosis caused by Perthes
      disease tended to have a better outcome than those caused as a complication of
      treatment for hip dysplasia. A computer model based on radiographic measurements
      was useful in planning the placement of the transfer for biomechanical
      efficiency. The surgical technique and osteotomy planning is described. Our goal
      is to review (1) the effectiveness of our surgical procedure, (2) whether
      deformity etiology influences outcome, (3) the best way to achieve optimal
      biomechanical efficiency, and (4) how software assisted planning can assist in
      surgical planning.

PMID- 15864038
TI  - Surgical treatment of the severe sequelae of infantile septic arthritis of the
      hip.
AB  - We retrospectively reviewed 45 hips in 43 patients with severe sequelae of
      infantile septic arthritis of the hip to compare the efficacy of various hip
      reconstructive and salvage surgeries, and to propose an algorithmic treatment
      protocol for the different types. Ten hips were classified as Choi Type IIIA,
      three as Type IIIB, 14 as Type IVA, and 18 as Type IVB sequelae. A total of 78
      hip surgeries and 18 limb-length equalizations (three contralateral femoral
      epiphysiodesis and 15 ipsilateral femoral and/or tibial lengthenings) were done.
      The first surgical reconstructions were done at an average age of 5.9 years
      (range, 1.1-14.8 years), with a 9.5-year average followup. Type IIIA hips had
      better functional results than the other types. In Type III hips, early
      realignment osteotomy of the proximal femur or bone-grafting of the
      pseudarthrosis was indicated. In Type IVB hips, satisfactory results were
      observed in only five of 10 hips treated by trochanteric arthroplasty compared
      with satisfactory results in all four hips treated by Ilizarov's hip
      reconstruction osteotomy. The latter operation seems to be better indicated in
      older patients with Type IVB hips, or with Type IVA hips in which previous
      reconstructive surgery was unsuccessful.

PMID- 15864039
TI  - Location of treatment of supracondylar fractures of the humerus in children.
AB  - A change in the locations where children are treated for supracondylar fractures
      of the humerus has occurred during the past 13 years. Pediatric orthopaedic
      surgeons at specialist centers are seeing an increased number of such fractures.
      In New England, the number of supracondylar fractures of the humerus treated by
      closed reduction and percutaneous pinning has remained relatively constant
      between 1991 and 1999 with a range of 276 to 346 fractures per year, averaging
      320 per year. In 1991, 63% of patients were treated by general orthopaedic
      surgeons in a nonspecialist setting. By 1999, 68% of the fractures were treated
      at centers with pediatric orthopaedic specialists available whereas only 32% were
      treated in a general orthopaedic setting. Associated with this change is a
      decreased length of stay from 2.2 (+/- 0.6) days in nonspecialist centers to 1.4
      (+/- 0.4) days average in specialist centers.

PMID- 15864040
TI  - Operative treatment of femoral shaft fractures in children and adolescents.
AB  - Although femoral shaft fractures constitute fewer than 2% of all fractures in
      children and adolescents, their treatment has produced many pieces of literature
      and years of controversy. Prevailing opinion has favored nonoperative and
      operative treatment, and a variety of techniques have been advocated to avoid
      complications such as nonunion, limb-length discrepancy, malalignment,
      osteonecrosis, and growth disturbance. Currently, operative methods of treatment
      generally are favored to allow early ambulation and shorter hospital stays and to
      avoid detrimental psychological and social effects often associated with
      prolonged nonoperative treatment, and to avoid complications. Options for
      operative fixation include external fixators, flexible and locked intramedullary
      nails, and compression and bridge plating. Although all of these can obtain good
      results in particular situations, there is no clear consensus of the indications
      for each. My choice for fixation of each fracture is based on consideration of a
      number of factors, including the age and size of the child, associated injuries,
      the location and pattern of the fracture, and the social situation of the child.
      In general, I prefer flexible nailing for younger children (6-10 years old) and
      locked nailing for adolescents at or near skeletal maturity. Bridge plating may
      be chosen for segmental, grossly comminuted fractures, whereas external fixation
      usually is reserved for severely comminuted or severe open fractures for which
      internal fixation is not appropriate.

PMID- 15864041
TI  - The extended anterolateral acromial approach allows minimally invasive access to
      the proximal humerus.
AB  - Lateral approaches to the proximal humerus have been limited by the position of
      the axillary nerve. Extensive surgical dissection through a deltopectoral
      approach may further damage the remaining tenuous blood supply in comminuted
      fractures. The purpose of our study was to explore a direct anterolateral, less
      invasive approach to the proximal humerus. Twenty cadaver shoulders were
      dissected using the extended anterolateral acromial approach through the anterior
      deltoid raphe. Multiple parameters were measured regarding the axillary nerve.
      The nerve was easily palpable in all specimens as it exited the quadrilateral
      space, and predictably was found and protected deep to the raphe, approximately
      35 mm from the prominence of the greater tuberosity. Examination of the entire
      anterior nerve revealed that no branches besides the main motor trunk crossed the
      deltoid raphe. Subsequently, this approach was used in 16 patients with proximal
      humerus fractures, none of whom has had complications related to the surgical
      approach. This minimally invasive surgical approach seems to be safe, and may be
      useful in treating proximal humerus fractures.

PMID- 15864042
TI  - MRI findings in throwing shoulders: abnormalities in professional handball
      players.
AB  - Shoulders of throwing athletes are highly stressed joints and likely to have more
      structural abnormalities seen on magnetic resonance imaging scans. Prevalence and
      type of structural abnormalities, especially abnormalities of the rotator cuff
      tendons and the superolateral humeral head, and correlation of magnetic resonance
      imaging findings with symptoms and clinical tests, are not well known. Throwing
      and nonthrowing (symptomatic and asymptomatic) shoulders of 30 fully competitive
      professional handball players and 20 dominant shoulders of randomly selected
      volunteers were evaluated for comparison clinically and with magnetic resonance
      imaging. An average of seven abnormal magnetic resonance imaging findings was
      observed in the throwing shoulders; more than in the nonthrowing and the control
      shoulders. Although 93% of the throwing shoulders had abnormal magnetic resonance
      imaging findings, only 37% were symptomatic. Partial rotator cuff tears and
      mainly superolateral osteochondral defects of the humeral head were identified as
      typical throwing lesions. Symptoms correlated poorly with abnormalities seen on
      magnetic resonance imaging scans and findings from clinical tests. This suggests
      that the evaluation of an athlete's throwing shoulder should be done very
      thoroughly and should not be based mainly on abnormalities seen on magnetic
      resonance imaging scans.

PMID- 15864043
TI  - No correlation between trapeziometacarpal arthritis and abductor pollicis longus
      insertion.
AB  - The primary hypothesis of this study is that supernumerary slips of the abductor
      pollicis longus (particularly those slips inserting distal to the
      trapeziometacarpal joint) increase the risk of trapeziometacarpal osteoarthritis
      on account of increased transarticular forces. Other hypotheses surmised that age
      and female gender were directly correlated with severity of arthritis. We did
      cadaveric dissection of the distal first dorsal compartment in 61 specimens,
      noting the cadaveric age, gender, and number and insertion sites of abductor
      pollicis longus tendon slips. Each variable was statistically correlated with
      visual grade of trapeziometacarpal arthritis. The median number of abductor
      pollicis longus tendon slips in these cadaveric hands was three (range, 1-4).
      Seventy-nine percent of the hands had a digastric-type insertion into the
      abductor pollicis brevis. Ninety percent had an insertion into the trapezium. All
      hands possessed an insertion into the base of the first metacarpal. Age and
      female gender were directly correlated with severity of arthritis. No other
      correlations existed. We conclude that trapeziometacarpal joint arthritis
      progresses with age and occurs independently of any aspect of abductor pollicis
      longus insertion. Based on our results, we do not recommend surgical release of
      these supernumerary abductor pollicis longus tendon slips for the treatment of
      trapeziometacarpal osteoarthritis.

PMID- 15864044
TI  - Does three-dimensional computer simulation improve results of scaphoid nonunion
      surgery?
AB  - The purpose of this study was to clarify the effectiveness of the three
      dimensional computer simulations in scaphoid nonunion surgery. Seven consecutive
      clinical patients with scaphoid nonunion at the middle third comprised the study
      group. Surface models of the scaphoid were constructed on the computer using
      computed tomography data of the bilateral wrists in neutral position. The distal
      and proximal fragments of the nonunion model were matched to the mirror image of
      the contralateral scaphoid model. The rotation of the distal fragment relative to
      the proximal fragment was calculated, and reduction of the displaced fragment of
      the scaphoid nonunion was simulated. Similarly, the estimated bone defect and the
      appropriate site and direction of the screw insertion were simulated. Full-sized
      hard models of the bone, including a model with simulated reduction and screw
      insertion, then were made using stereolithography based on the computer data. In
      the actual surgery, reduction, bone grafting, and screw insertion were achieved
      using the hard models as guides. All the patients obtained solid bone fusion and
      substantial clinical improvement with normalized scapholunate and radiolunate
      angles after surgery. Three-dimensional computer simulations were found as useful
      for accurate correction of scaphoid nonunions and proper screw placement, which
      consequently leads to good clinical results.

PMID- 15864045
TI  - Surgical treatment of neck hyperextension in myopathies.
AB  - Neck hyperextension occurs in relation to several myopathies. It is a progressive
      increase of lordosis associated with a limitation in flexion of the cervical
      spine, forcing the patient to assume awkward compensatory postures to maintain
      balance and level vision. We evaluated operative complications, degree of
      correction, achievement of a solid arthrodesis, maintenance of the correction,
      and clinical assessment of seven patients. All had surgery in which the
      interspinous processes between C2-C7 were opened in a posterior approach and bone
      graft wedges driven into them to maintain the correction. The mean age of
      patients at the time of surgical intervention was 16.5 years (range, 10-28
      years). The average followup was 10.4 years (range, 2.4-16.5 years). No major
      surgical complications occurred. After surgery, the average angle between C2-C7
      in neutral position had decreased from 50.7 degrees (range, 40 degrees -70
      degrees ) to 21.4 (range, 2 degrees -50 degrees ). The range of motion in the C1
      C2 joint remained unaffected, whereas it decreased in C2-C7 from 33.5 degrees
      (range, 15 degrees -64 degrees ) to 1.8 degrees (range, 0 degrees -8 degrees ). A
      solid arthrodesis was achieved in all patients The followup showed significant
      clinical improvement of posture in all patients. The operating technique used
      proved to be safe and effective.

PMID- 15864046
TI  - Not all spondylolisthesis grading instruments are reliable.
AB  - Spondylolisthesis is the slippage of one vertebral body on an adjacent level, and
      occurs commonly at the lumbosacral junction in children. Many radiographic
      measurement instruments have been described to predict progression and need for
      intervention. We evaluated the reliability of eight common grading instruments.
      Four raters reviewed 30 lateral radiographs of the lumbar spine in patients with
      spondylolisthesis. Each rater measured each film twice, and had mean individual
      correlation coefficients of at least 0.76 (range, 0.76-0.91). Only three
      measurements had interobserver correlations greater than 0.75 (slip percentage,
      Meyerding's grade, and sacral inclination), which corresponded to excellent
      reliability. For intraobserver reliability, six measurements had correlations
      greater than 0.75 (all except kyphosis angle and lumbar index), indicating
      excellent agreement. Slip percent, Meyerding's grade, and sacral inclination had
      excellent interobserver agreement and intraobserver agreement.

PMID- 15864047
TI  - Computed tomographic analysis of bone support for three acetabular cup designs.
AB  - The initial stability and long-term survivorship of cementless acetabular
      components is partially dependent on bone-prosthesis contact patterns. This study
      addresses the question: What are the differences in contact patterns for
      hemispheric, dual geometry, and spiked designs? Quantitative and qualitative
      assessment of contact patterns was achieved using a novel, nondestructive
      computed tomography-based analysis. Eighteen cadaveric hemipelvis specimens were
      randomly assigned to receive one of three cup designs. The mean amount of cup
      contact was 48.6% in the hemisphere group, 31.9% in the dual geometry group, and
      35.1 percent in the spiked group. The hemispheric design showed more contact and
      a more uniform contact pattern than the dual geometry design. The dual geometry
      design featured a tight fit at the rim of the implant. In the spiked group, the
      amount of bone-prosthesis contact was affected by the distance that the spikes
      advanced into the pelvic bone. This nondestructive imaging technique has
      potential future uses in in vitro and in vivo studies.

PMID- 15864048
TI  - Increased cytokine secretion in patients with failed implants compared with
      patients with primary implants.
AB  - All total joint replacements generate wear debris; yet, some implant prostheses
      fail while others survive despite the presence of ultrahigh molecular weight
      polyethylene particulate. It was hypothesized that patients with failed hip
      implants who have osteolysis will secrete higher inflammatory cytokines than
      patients receiving total joint replacements. Our study evaluated the peripheral
      blood monocyte response to varying polyethylene particle volume ratios through
      cytokine quantification in two patient populations: patients having revision
      surgery for failed total hip replacements (failed implant group) and patients
      having primary total hip surgery for osteoarthritis of the hip (primary implant
      group). We observed elevation of all three proinflammatory cytokines tested
      (interleukin-6, interleukin-1, and tumor necrosis factor-alpha) in response to
      polyethylene particulate challenge when compared with the controls in both
      patient groups. The population with failed implants also had a higher absolute
      cytokine response to polyethylene exposure compared with the control patients
      having primary implants. These findings suggest that patients with failed
      implants have a greater inflammatory cytokine response to polyethylene than seen
      in patients with primary implants.

PMID- 15864049
TI  - The 20-year outcome of the charnley arthroplasty in younger and older patients.
AB  - The purpose of this study is to present the 20-year outcome of 206 Charnley low
      friction arthroplasties done by the same surgeon on 181 patients who were
      separated into two age groups (younger and older). In Group A (76 patients, 92
      hips) the mean age at surgery was 44 years (range, 24-55 years), and in Group B
      (105 patients, 114 hips) the mean age at surgery was 65 years (range, 56-82
      years). All patients were evaluated clinically and radiographically. At final
      followup, 71 patients (87 hips) in Group A and 90 patients (99 hips) in Group B
      were available for study. The overall failure rate for the hips of Group A was
      37.9%, and the overall failure rate for the hips of Group B was 20%. The main
      cause of failure in Group A was aseptic loosening of the components and breakage
      of the femoral stem, whereas in Group B the main cause of failure was deep
      infection. We concluded that by eliminating the above factors, and using new
      cementing techniques and improved implants, the 20-year results of this
      arthroplasty would be better. Our results show that the Charnley arthroplasty is
      a reliable procedure for hip replacement, even in younger patients.

PMID- 15864050
TI  - Reproducible assessment of radiolucent lines in total knee arthroplasty.
AB  - The Knee Society Total Knee Arthroplasty Radiographic Evaluation and Scoring
      System was introduced to encourage uniform reporting of radiographic outcome.
      However, the method for evaluation of radiolucent lines has been shown to be
      unreliable. Because it has been shown that reducing the complexity of
      classification systems increases reliability and reproducibility, we questioned
      whether a simplification of the Radiographic Evaluation and Scoring System would
      improve reliability and reproducibility. A new system for assessment of
      radiolucent lines was introduced, and the interobserver reliability and
      intraobserver reproducibility were studied in 100 patients with 120 total knee
      replacements. For the new system the mean kappa intraobserver reproducibility
      coefficient was 0.71 (range, 0.62-0.85) for the femoral component, 0.86 (range,
      0.80-0.96) for the tibial component, and 0.58 (range, 0.46-0.75) for the patella
      prosthesis. The mean interobserver reliability coefficient among three observers
      was 0.61 (range, 0.45-0.72) for the femoral component, 0.82 (range, 0.73-0.88)
      for the tibial component, and 0.58 (range, 0.43-0.72) for the patella prosthesis.
      The new system for assessment of radiolucent lines increased reliability and
      reproducibility and should supplement the Knee Society's Radiographic Evaluation
      and Scoring System.

PMID- 15864051
TI  - Using self-assessed health to predict patient outcomes after total knee
      replacement.
AB  - Self-assessed health status has been shown to be a powerful predictor of
      mortality, service use, and total cost of medical care treatment. We investigated
      the potential for self-assessed health to further serve as a predictor of
      improvement in health status after a clinical intervention. Using the five
      category measure of self-assessed health (excellent, very good, good, fair, or
      poor), we examined patients' improvements in health status after total knee
      arthroplasty in each of the WOMAC-defined categories for health status in
      patients. The results indicate that the greater patients rated their preoperative
      health, the greater their postoperative improvement. The results suggest that a
      simple process of asking patients to rate their own health in a presurgery clinic
      could be a powerful tool in predicting patient outcome. This also suggests that
      by stratifying preoperative self-assessed health, potential improvements in
      health status will be more fully captured.

PMID- 15864052
TI  - Axial radiography of the distal femur to assess rotational alignment in total
      knee arthroplasty.
AB  - A method for taking an axial radiograph of the distal femur was developed to see
      the epicondyles and posterior condyles of the femur. It was hypothesized that
      these radiographs would be acceptable for evaluating rotational alignment in
      total knee arthroplasty with comparable reproducibility and good correlation to
      the results obtained with computed tomography images. Radiographs were obtained
      of 50 knees in 32 patients having total knee arthroplasty. The radiographs were
      taken while the patients were with the knee in 90 degrees flexion. The angle
      between the clinical epicondylar axis and the posterior condylar axis (twist
      angle) was measured and compared with the results obtained by conventional
      computed tomography. The interobserver variation in the axial radiography was
      less than or comparable to the computed tomography method. The mean discrepancy
      between the two methods (+/- standard deviation) was 0.5 degrees +/- 0.4 degrees
      (range, 0-1.9 degrees ), and a strong correlation was observed. This plain
      radiography is acceptable for evaluation of femoral component rotation with
      comparable reproducibility and correlation to the results with computed
      tomography. It has several advantages regarding cost, radiation dose, and lack of
      scatter when used for postoperative assessment.

PMID- 15864053
TI  - Limb positioning is critical for defining patellofemoral alignment and femoral
      shape.
AB  - The source of patellofemoral pain is a common orthopaedic complaint that often is
      difficult to determine because of the lack of correlation between symptoms and
      specific clinical measurements. Excessive joint contact stresses resulting from
      patellofemoral malalignment and pathologic femoral shape often are associated
      with this pain. These measures are likely sensitive to the limb position
      (orientation and position relative to the imaging system with which they are
      quantified). Because of this sensitivity, the measures have large variations and
      do not show correlations with subjective symptoms. The purpose of this study was
      to determine if varying limb position resulted in significant changes in standard
      clinical measures of patellofemoral alignment and femoral shape. This dependence
      was investigated by simulating alterations in limb position through resectioning
      of three-dimensional magnetic resonance image sets (20 healthy knees) to create
      axial images with altered orientation (eight images) or location (four images)
      relative to a fixed reference. By quantifying the variability of the clinical
      measures across all images, it was determined that simulated alterations in limb
      position produced greater variability in femoral shape and patellofemoral
      alignment measures than the variability seen across control subjects. This
      indicated that a standardized method for establishing limb position relative to
      the imager is warranted.

PMID- 15864054
TI  - Magnetic resonance imaging AIDS in detecting concomitant injuries in patients
      with tibial spine fractures.
AB  - Tibial spine fracture is one of the clinical entities of anterior cruciate
      ligament injury, and sometimes is accompanied by concomitant injuries. The
      purpose of this study was to review magnetic resonance imaging findings in 25
      patients with tibial spine fractures and to assess the use of these findings in
      determining the presence of concomitant injuries. Of these 25 patients, 10 were
      children and 15 were considered adults (average age, 24.2 years old). A
      radiologist retrospectively assessed tibial spine fractures and concomitant
      injuries, such as meniscus and ligament injuries. Comparing the pediatric and
      adult groups, all additional ligament injuries were confirmed in the adult group.
      In the pediatric group, only one patient with a chronic injury had meniscus
      injuries. There were no meniscus tears in pediatric patients with acute injuries.
      In the adult group, three medial meniscus tears were found in two patients with
      chronic injuries and one patient with acute injury, and four lateral meniscus
      tears were found in one patient with a chronic injury and three patients with
      acute injuries. Because tibial spine fractures in adults may be accompanied by
      concomitant injuries requiring surgical treatment, magnetic resonance imaging is
      recommended.

PMID- 15864055
TI  - Heel cord advancement combined with Vulpius' lengthening of the gastrocnemius.
AB  - The results of Achilles tendon lengthening to treat spastic pes equinus deformity
      are less than satisfactory, with high recurrence rates. To improve the outcome,
      heel cord advancement can be done. In the current study, the patients with severe
      contracture of the Achilles tendon were treated by heel cord advancement.
      Additional lengthening of the gastrocnemius muscle using the Vulpius technique
      was done to reattach the Achilles tendon to the calcaneus. Seventeen patients (20
      feet) with spastic pes equinus deformities were treated with this technique, and
      satisfactory midterm postoperative results were obtained. The mean age of the
      patients at surgery was 10 years, and the mean duration of followup after surgery
      was 8 years. The mean tibioplantar angle decreased postoperatively, and there
      were no recurrences of pes equinus deformity and no appearance of pes calcaneus
      deformity. Walking ability improved in two patients and did not deteriorate in
      any of the patients. Seven of the patients were able to stand on only the
      affected foot after the operation. Our technique provides good correction of an
      equinus deformity with no recurrence, and with improvement of the physical
      activity level.

PMID- 15864056
TI  - Pelvic reconstruction for massive acetabular insufficiency.
AB  - Joint reconstruction for pelvic discontinuity because of massive acetabular
      insufficiency presents a significant surgical challenge. Using retrograde
      inserted Steinmann pins to rebuild the dome may be associated with early implant
      failure because of insufficient mechanical stability and neurovascular injury
      resulting from pin misplacement. Retrograde pins cannot be placed completely
      across the pelvic defect. We hypothesized that large Steinmann pins placed
      anterograde under direct vision from the iliac crest completely across the
      acetabular column and floor defects would minimize the risk of early failure, and
      could be placed safely without the use of fluoroscopy in combination with a
      posterior hip approach. The purpose of our study was to review the mechanical
      failure and complication rates of nine patients (10 hips) treated between 1996
      and 2002 for pelvic discontinuity using this pin placement technique to reinforce
      a cemented roof ring hip reconstruction done via a posterior approach. None of
      the patients had implant loosening or failure, there were no neurovascular
      complications, and no perioperative deaths. One patient required cup revision for
      recurrent dislocation. All patients were bedridden or wheelchair-bound before
      surgery, but regained independent household walking by 6 weeks postoperatively.
      Reinforcing the acetabulum with a lattice girder of anterograde pins provides
      safe and effective hip reconstruction.

PMID- 15864057
TI  - Fractures of the distal humerus in the elderly: is internal fixation the
      treatment of choice?
AB  - The incidence of osteoporotic fractures of the distal humerus is increasing, and
      the treatment of these injuries merits closer review. We assessed the results of
      28 elderly patients (29 fractures) with a mean age of 85 years (range, 75-100
      years). Open reduction and internal fixation was done on 21 elbows, and eight
      elbows were treated nonoperatively. Orthopaedic Trauma Association grading showed
      that the group treated with internal fixation had favorable results (three
      excellent, nine good, seven fair, and two poor) compared with the nonoperatively
      treated group (zero excellent, two good, three fair, and three poor). Mean loss
      of extension and mean flexion were better in the surgically treated patients
      (23.5 degrees and 99 degrees ) than in the nonoperatively treated patients (33.5
      degrees and 71 degrees ). Substantial pain relief (mild or no pain) was achieved
      in a higher proportion (52%) in the surgically treated group than in the
      nonoperatively treated group (25%). Anatomic restoration of distal humeral tilt
      and articular congruity also were better in the surgically treated patients.
      Rates of complications were observed to be comparable to those described in the
      literature for younger patients. These findings reflect the relevance of surgical
      fixation of such fractures in this age group highlighting the need for additional
      clinical studies.

PMID- 15864058
TI  - Reduction in Gsalpha induces osteogenic differentiation in human mesenchymal stem
      cells.
AB  - We hypothesized that a decrease in Gsalpha expression occurs with osteogenic
      differentiation and that when Gsalpha expression was decreased by antisense
      oligonucleotides or direct inhibition of protein kinase A there was a concomitant
      increase in Runx2/Cbfa1. We also investigated the mechanism involved in the
      change in Runx2/Cbfa1 levels and whether the expression of other genes known to
      be involved in bone formation was altered. There was a decrease in Gsalpha
      expression with osteogenic differentiation and antisense oligonucleotides, and
      protein kinase A inhibition led to increased expression and DNA binding of the
      osteoblast-specific Runx2/Cbfa1. Additionally, with decreased Gsalpha expression
      or protein kinase A inhibition, Runx2/Cbfa1 protein was serine phosphorylated and
      ubiquitinated less. Microarray analysis, after the addition of antisense Gsalpha,
      showed a more than 10-fold increase in collagen Type I Alpha 2 mRNA (a target of
      Runx2/Cbfa1). These data show that reduced expression of Gsalpha can induce an
      osteoblast-like phenotype. The results also indicate a potential pathophysiologic
      role in patients with heterozygous inactivating mutations in GNAS1, the gene for
      the alpha chain (Gsalpha) of the heterotrimeric G protein, present in three
      disorders with ectopic intramembranous bone: Albright's hereditary
      osteodystrophy, progressive osseous heteroplasia, and osteoma cutis.

PMID- 15864059
TI  - Native hyaluronan produces less hypersensitivity than cross-linked hyaluronan.
AB  - Hyaluronan has been used in patients with osteoarthritis to relieve the painful
      symptoms associated with this condition. The native form of hyaluronan and
      artificially cross-linked forms of hyaluronan (such as Hylan G-F 20) are widely
      used brands that are approved by the Food and Drug Administration for use in
      patients with osteoarthritis. Clinical evidence suggests that some of these
      hyaluronan products may induce an antigenic reaction in some patients. Therefore,
      it was critical to do controlled studies on the potential antigenic reaction
      induced by these substances. The purpose of this study was to assess the
      immunologic reactions resulting from the native or cross-linked forms of
      hyaluronan products in guinea pigs after subcutaneous injection. Guinea pigs were
      sensitized to hyaluronan via three subcutaneous injections. Active cutaneous or
      delayed-type hypersensitivity to hyaluronan was studied. The elicitation of
      antihyaluronan antibodies also was studied by indirect competitive ELISAs. Our
      results showed that Synvisc induced delayed-type hypersensitivity in guinea pigs,
      however, no hypersensitivity to the native hyaluronan was observed. This delayed
      type hypersensitivity reaction to the cross-linked form of hyaluronan was
      confirmed by our finding that sera from guinea pigs sensitized to the cross
      linked form showed increased antihyaluronan-specific antibodies in competitive
      ELISAs. In a direct comparison, the native form of hyaluronan produced
      significantly less hypersensitivity than an artificially cross-linked form of
      high molecular weight hyaluronan. The hypersensitivity to the cross-linked form
      of hyaluronan can be explained in part by its elicitation of ant-hyaluronan
      immunoglobulins in sensitized animals.

PMID- 15864060
TI  - Oxidative stress after muscle damage from immobilization and remobilization
      occurs locally and systemically.
AB  - Higher oxidative stress reportedly plays a key role in muscle damage caused by
      immobilization and subsequent remobilization. However, we have no clear
      understanding regarding oxidative stress during immobilization and
      remobilization. The purpose of this study was to clarify the characteristics of
      oxidative stress by measuring oxidative stress locally and systemically. Twenty
      three New Zealand White rabbits were used in this study. Blood samples were
      collected on Days 1, 3, 7, 14, and 21 of immobilization, and Days 1, 2, 3, and 4
      of remobilization. The soleus muscles in immobilized and nonimmobilized limbs
      were harvested on Day 21 of immobilization and Day 7 or Day 14 of remobilization.
      Muscle wet weight was determined as the indicator of muscle atrophy. The levels
      of lipid peroxidation and glutathione in plasma and soleus muscles were measured.
      Immobilization and remobilization induced an increase in the lipid peroxidation
      levels and a decrease in glutathione levels in muscle and blood. These findings
      suggest that oxidative stress occurs locally and systemically, lasts throughout
      the immobilization period, but peaks at the early phase of remobilization.

PMID- 15864061
TI  - Ultraporous beta-tricalcium phosphate is well incorporated in small cavitary
      defects.
AB  - Numerous bone graft substitutes are available as alternatives to autologous and
      allograft bone grafts. The use of ultraporous beta-tricalcium phosphate for
      cavitary bone defects in our institution was based on the hypothesis that it
      would have gradual but complete incorporation over several months, similar to the
      smooth transition seen in animal models. This retrospective, uncontrolled study
      reviews 24 patients who had bone grafting of a cavitary defect with ultraporous
      beta-tricalcium phosphate mixed with local blood. Radiographically, resorption
      and trabeculation increased steadily with time, with trabeculation lagging
      slightly behind resorption. Resorption and trabeculation were more advanced at
      times beyond 6 weeks in small defects (< 43 cm) compared with large defects (>/=
      43 cm). The presence of peripheral radiolucency seen early around nearly all
      grafts disappeared in small lesions by 1 year, but still was visible in larger
      lesions at the latest followup. Bone renewal seems to correspond temporally with
      gradual replacement of graft material, but incorporation is not complete even at
      1 year in large defects. Clinically, there is a low rate of complications
      associated with the use of ultraporous beta-tricalcium phosphate, and patients
      progressed to unrestricted activities of daily living and recreational activities
      within 3 months.

PMID- 15864062
TI  - Case report: Reconstruction of an intercalary defect with bone transport after
      resection of Ewing's sarcoma.
AB  - We report a 13-year-old girl with Ewing's sarcoma of the tibia who was treated
      with multiagent chemotherapy, followed by local control tumor surgery consisting
      of wide resection of the tumor and bone transport with distraction osteogenesis
      for reconstruction. The bone defect created by resection was 13 cm long and was
      replaced by bone transport using a monolateral external fixator. Evaluation of
      the resected specimen revealed wide tumor-free margins with 100% chemonecrosis. A
      planned Harmon-type autogenous bone grafting between the middle and proximal
      segments of the tibia (docking site) was done primarily after docking occurred,
      and a solid union was obtained by 23 months after resection. The bone healing
      index (treatment index) was 54 days/1 cm distraction, which is indicative of slow
      healing. Clinical evaluation of the affected extremity using the Musculoskeletal
      Tumor Society rating system revealed 80% normal functional capability.
      Indications for bone transport in reconstruction of bone defects created by wide
      resection of bone sarcomas are discussed. In retrospect, we have concerns
      regarding the suitability of this technique in the setting of diaphyseal sarcoma
      reconstruction in patients with Ewing's sarcoma who require aggressive and
      intense multiagent chemotherapy.

PMID- 15864063
TI  - Case report: Periosteal Ewing's sarcoma: case report and literature review.
AB  - Ewing's sarcoma is a round-cell tumor that arises most often in a medullary
      cavity. This neoplasm is uncommon in a subperiosteal location. We report a new
      case of a 12-year-old boy with a periosteal Ewing's sarcoma, located in the
      femur, who was treated by cortical segmental resection associated with
      chemotherapy. Two years after surgery the patient was free of disease. In
      reviewing the literature of 29 cases, it seems the prognosis is better in
      periosteal compared with intramedullary Ewing's sarcoma.

PMID- 15864064
TI  - Case report: A rare case of Ewing's sarcoma and osteosarcoma at different sites
      10 years apart.
AB  - Ewing's sarcoma of bone and osteosarcoma are rare tumors. A combination of high
      grade osteosarcoma and Ewing's sarcoma of bone in anatomically unrelated sites is
      unique, especially in the absence of previous radiation or retinoblastoma. We
      present a patient with a rare case of Ewing's sarcoma of the scapula that showed
      no evidence of recurrence (after 10 years of continued followup) and who
      subsequently presented with a primary osteosarcoma of the femur.

PMID- 15864066
TI  - Leg pain in a 39-year-old man.

PMID- 15864065
TI  - Case report: Bone metastases from fallopian tube carcinoma.
AB  - Fallopian tube carcinoma is a rare gynecologic tumor that has metastasized to
      bone in only one documented case. This case report is of a 56-year-old woman with
      a primary fallopian tube cancer metastasizing to her right femur and rib cage.
      This patient was referred to our orthopaedic department from her gynecologic
      oncologist. A total abdominal hysterectomy and bilateral salpingectomy and
      oophorectomy revealed fallopian tube cancer. After surgery, the patient had
      progressive right thigh pain with activity. Radiographs of the femur showed a
      lytic lesion in the right proximal femur diaphysis with erosion of the medial
      cortex. We did an open biopsy and curettage of the lesion and intramedullary rod
      placement. The biopsy confirmed a metastatic lesion arising from the primary
      fallopian tube cancer. Currently, the patient is recovering and is receiving
      radiation and chemotherapy. In this case report, we discuss the presentation and
      treatment course of the patient and summarize the available literature on
      fallopian tube carcinomas.

PMID- 15864067
TI  - Isolation decreases physical and motivational aspects of morphine withdrawal.
AB  - Environmental manipulations such as social housing conditions of animals may play
      a role in the expression of individual differences in response to drugs. This
      study aimed to evaluate whether isolated and grouped mice develop different
      degrees of morphine dependence. Isolated and grouped mice were rendered morphine
      dependent employing two different methods of induction: a fast or slow protocol,
      both reaching the same maximum daily dose (100 mg/kg). Naloxone-induced morphine
      withdrawal was assessed using a modified Gellert-Holtzman scale and a conditioned
      place aversion (CPA) procedure. Isolated animals manifested fewer signs of
      physical dependence than grouped mice and only those receiving two daily morphine
      doses presented significantly higher scores on the Gellert-Holtzman scale than
      controls. Similarly, in CPA, although all morphine-treated animals developed
      aversion, its intensity was only significantly higher than in controls in grouped
      animals receiving two daily doses. Analgesic response, measured with the hot
      plate test, showed that isolated mice presented longer latencies to lick their
      paws (even without drug administration), suggesting that they had a higher level
      of endogenous opiates. It can be argued that isolated animals may be less
      sensitive to morphine than the non-isolated and therefore tolerate greater
      quantities or require more drug to produce the same effects. The results suggest
      that variability in the response to opiates could be affected by environmental
      manipulations.

PMID- 15864068
TI  - Effects of ultra-low doses of morphine, naloxone and ethanol on morphine state
      dependent memory of passive avoidance in mice.
AB  - This experiment examined and compared the effects of pre-test administration of
      morphine, naloxone and ethanol, at doses in the range of milligram/kg to those of
      nanogram/kg, on morphine state-dependent learning in a step-down passive
      avoidance task in mice. Morphine (5 mg/kg) administered before training impaired
      retention tested 24 hours later, but when the same dose of morphine was also
      administered before the test, the retention was significantly restored. Pre
      training administration of 10 or 20 ng/kg (i.p.) of morphine had no effect, but
      when co-administered with the same drug at 5 mg/kg (s.c.), it prevented
      significantly the memory recall improvement after the administration of morphine
      (5 mg/kg, s.c.) alone. In a parallel experiment, naloxone (5 mg/kg) prevented the
      memory recall improvement by morphine. However, the effects of naloxone at doses
      in the range of ng/kg were opposite to those of milligram doses of the same drug.
      Pre-test administration of ethanol (1 mg/kg) improved memory recall and mimicked
      the effects of pre-test morphine administration. At doses in the nanogram range,
      the effects of ethanol were opposite those of mg/kg of the drug. A review of the
      literature indicates that, for several drugs and chemicals, the effects of
      nanogram doses are the opposite of the effects of milligrams, because different
      doses have different sites as well as mechanisms of actions. In conclusion, from
      the above results one may suggest that, in determination of the dose-response of
      at least some drugs, the study of the effects of doses much lower than two orders
      of magnitude of the minimum effective dose are warranted.

PMID- 15864069
TI  - Evidence for PTZ-like cues as a function of time following treatment with
      chlordiazepoxide: implications for understanding tolerance and withdrawal.
AB  - The present study used a two-lever, drug-discrimination procedure to train rats
      to discriminate between the cues associated with 5 mg/kg of the anxiolytic,
      chlordiazepoxide (CDP) and 15 mg/kg of the anxiogenic, pentylenetetrazol (PTZ),
      to investigate the relationship between withdrawal and acute tolerance. Training
      doses of the two drugs were chosen so that rats responded about equally on both
      levers when tested on saline (SAL). Following acquisition of the discrimination,
      rats were injected with 10 mg/kg CDP and tested for lever choice at various
      intervals from 6 h to 192 h. These tests revealed that cues associated with CDP
      withdrawal lasted approximately three times longer than the cues associated with
      the drug's primary effects. At the shortest retest interval (6 h) after treatment
      with 10 mg/kg CDP, rats responded primarily on the CDP lever, followed by a shift
      to predominant responding on the PTZ lever at the 16 h and 24 h intervals before
      returning to predrug, baseline levels at the longer intervals (48-192 h). In
      order to investigate the relationship between tolerance and withdrawal to the cue
      properties of CDP, CDP dose-response curves were determined 24 h following
      treatment with SAL or 10 mg/kg CDP. Acute tolerance, as defined by a rightward,
      parallel shift in the dose-response function, was observed in the rats pretreated
      with CDP. Furthermore, it was evident that the baseline shift associated with CDP
      withdrawal, rather than a weaker drug cue, accounted for acute tolerance. The
      results from this study are relevant to evaluating the role positive and negative
      reinforcement play in motivating compulsive drug use.

PMID- 15864070
TI  - A comparison of the predictive therapeutic and undesired side-effects of the NMDA
      receptor antagonist, memantine, in mice.
AB  - Memantine (1-amino-3,5-dimethyl-adamantane) is the only clinically used NMDA (N
      methyl-D-aspartate) glutamate receptor antagonist. The present experiments were
      carried out to compare the dose-response for memantine's predictive therapeutic
      and side-effects in a variety of tests in C57BL/6J/Han mice, and to elucidate if
      tolerance may develop to them. Memantine produced a dose-dependent (2.5-15 mg/kg)
      antidepressant-like effect in the tail-suspension test (TST); this anti
      immobility effect of 15 mg/kg of memantine appeared to persist with its sub
      chronic administration (3 days, twice daily). Treatment with the same doses of
      memantine produced no effects on locomotor activity, and sub-chronic treatment
      with 15 mg/kg did not affect locomotor activity. Exploratory activity was
      assessed in the open field. Given acutely 5 min before the test, memantine
      reduced rearing (1.875-30 mg/kg), ambulation (7.5 and 30 mg/kg) and grooming (30
      mg/kg). These effects were more pronounced 35 min after its administration. As
      measured in three different tests, ataxia and stereotypy appeared only at the
      single dose of 30 mg/kg, 5 and 35 min after administration. In mice treated sub
      chronically with 30 mg/kg, the dose of 30 mg/kg increased ambulation, and
      continued to decrease rearing and grooming, but no signs of ataxia and stereotypy
      were detected. The present data indicate that different doses of memantine are
      required for the purportedly therapeutic and side-effects, and that tolerance may
      develop to the ataxic, but not anti-immobility actions.

PMID- 15864071
TI  - 5-HT(3) receptors, alcohol and aggressive behavior in mice.
AB  - Alcohol is a positive modulator at the 5-HT(3) receptor, which has been
      implicated in alcohol drinking, anxiety and aggression. The reported experiments
      explored the role of the 5-HT(3) receptor in aggressive behavior and alcohol
      heightened aggression. Male, CFW mice were trained to self-administer 1.0 g/kg of
      alcohol, after which they confronted an intruder. Half of the CFW mice exhibited
      consistently increased aggressive behavior after alcohol and were designated as
      showing alcohol-heightened aggression, the others showed no increase and were
      designated as showing alcohol non-heightened aggression. The 5-HT(3) antagonist,
      ondansetron (0.01-1.0 mg/kg), significantly reduced aggression in both groups of
      CFW mice without affecting non-aggressive behaviors. Zacopride also reduced
      aggression effectively in both groups of mice, but at high doses began to affect
      walking. Male B6SJL/F2 transgenic 5-HT(3) over-expressing mice (TG) and wild-type
      mice (WT) were tested for aggressive behavior in their home cage. In those
      individuals that fought in tests of resident-intruder aggression, no differences
      were found in aggression after alcohol intake. In tests of aggression without
      alcohol intake, zacopride reduced aggression in both TG and WT mice at a dose of
      56 mg/kg. Antagonism of 5-HT(3) receptors shows promising anti-aggressive
      effects, although these effects depend on the genetic background of the mice.

PMID- 15864072
TI  - Stress-induced hyperlocomotion as a confounding factor in anxiety and depression
      models in mice.
AB  - Chronic stress is broadly used to model anxiety and depression. However, in
      chronic stress models, anxiety- and depression-like behaviors might be masked by
      unspecific effects of stress. We tested whether chronic stress in mice can induce
      unspecific changes in locomotion, and whether these changes interfere with the
      measurement of anxiety and forced-swimming behaviors. Also, we studied these
      latter behaviors in relation to the duration of stress, the lighting conditions
      during testing, and after the injection of diazepam. We employed a 4-week chronic
      stress paradigm, adopted from a model of stress-induced anhedonia and a 1-week
      subchronic stress, both consisting of rat exposure, restraint stress and tail
      suspension. Chronically stressed mice, tested under bright and moderate
      illumination, exhibited 'anxiolytic-like' behavior along with prolonged swimming
      and hyperactivity. These behaviors were not detectable under weak illumination or
      after the injection of diazepam (0.25 mg/kg). Instead, normal locomotion,
      increased anxiety and inhibited swimming were revealed under these conditions.
      Thus, chronic stress can induce hyperlocomotion in mice, which is triggered by
      acute stressors such as light, and interferes with the evaluation of anxiety and
      forced swimming. One week of stress did not change locomotion and forced
      swimming, and increased anxiety irrespective of illumination applied during
      testing. Our data can possibly explain previously reported contradictions in the
      behavioral testing of mice with chronic stress models of anxiety and depression.

PMID- 15864073
TI  - The dopamine D(3) receptor-preferring partial agonist BP 897 dose-dependently
      attenuates the expression of amphetamine-conditioned place preference in rats.
AB  - Previously we reported that systemic administration of the dopamine D3 receptor
      preferring partial agonist BP 897 blocked the expression, but not the
      acquisition, of amphetamine-conditioned activity. This suggested the hypothesis
      that BP 897 would block the expression, but not the acquisition, of amphetamine
      conditioned place preference (CPP). Thus, during preconditioning rats had access
      to two chambers connected by a tunnel for three 15-min sessions. During eight
      conditioning days with the tunnel blocked, one chamber was paired with drug
      administration for four 30-min sessions, alternating with pairing of the other
      chamber with saline administration. In a drug-free test session, time on the drug
      paired side was compared to time spent there in preconditioning; a significant
      increase was defined as a place preference. Systemic amphetamine (2.0 mg/kg) or
      amphetamine+BP 897 (1.0, 2.0 mg/kg) during conditioning produced a significant
      place preference, while administration of BP 897 (1.0 or 2.0 but not 0.5 mg/kg)
      during the test blocked the amphetamine-CPP. There was no evidence that BP 897
      produced a conditioned aversion. Results supported the hypothesis that BP 897
      would block expression, but not acquisition, of amphetamine-CPP.

PMID- 15864074
TI  - Effects of the 5-HT(1A) agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8
      OH-DPAT) on cocaine choice in cynomolgus monkeys.
AB  - Drugs that alter brain serotonin (5-HT) function can modulate the behavioral
      effects of cocaine, but the underlying receptor mechanisms are poorly understood.
      The present study examined the effects of the selective 5-HT1A receptor agonist
      (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.01-0.1 mg/kg, i.v.) on
      cocaine self-administration in the context of a choice procedure. Five adult male
      cynomolgus monkeys self-administered cocaine (saline, 0.003-0.03 mg/kg per
      injection) under a concurrent fixed-ratio 50 schedule of food (1-g banana
      flavored pellets) and cocaine presentation. Allocation of responses to the
      cocaine-associated lever (cocaine choice) increased in a dose-related manner from
      < or =20% of total responses when saline or 0.003 mg/kg per injection cocaine was
      the alternative to food to > or =75% when 0.03 mg/kg per injection cocaine was
      available. In four of five monkeys, when choice was between a low cocaine dose
      and food, 0.01 mg/kg 8-OH-DPAT increased injection-lever responding. At cocaine
      doses which occasioned > or =75% cocaine choice, 8-OH-DPAT did not alter response
      allocation. In the fifth monkey, 8-OH-DPAT only decreased injection-lever
      responding. When choice was between saline and food, 8-OH-DPAT did not reliably
      shift responding to the injection lever, except at doses that disrupted operant
      performance. These results suggest that a 5-HT1A receptor agonist can increase
      the reinforcing strength of a low cocaine dose relative to a concurrently
      available non-drug reinforcer.

PMID- 15864076
TI  - Smallpox vaccination: a conundrum of risks and outcomes.

PMID- 15864077
TI  - On the benefit of breaking the rules.

PMID- 15864078
TI  - Does fish oil supplementation in pregnancy reduce the risk of allergic disease in
      infants?
AB  - PURPOSE OF REVIEW: Parallel increases in many inflammatory diseases over the last
      40 years suggest that common environmental changes are promoting inflammatory
      immune responses and/or inhibiting the processes that normally keep these in
      check. One key change during this period has been declining intakes of anti
      inflammatory dietary factors, including omega-3 polyunsaturated fatty acids (n-3
      PUFA). As allergic diseases often first manifest in early infancy, prevention
      strategies need to be targeted early, even in utero. This review will examine
      recent evidence for the use of fish oil during this early period as a primary
      prevention strategy for allergic disease. RECENT FINDINGS: N-3 PUFA have well
      documented anti-inflammatory effects in vitro and have also been demonstrated to
      have health benefits in a range of chronic inflammatory diseases, including
      cardiovascular disease, rheumatoid arthritis and diabetes, supporting their role
      in modulating inflammation in vivo. Although the effects of fish oil
      supplementation in established allergic disease are less convincing, there is
      accumulating evidence that dietary n-3 PUFA may have greater effects before
      allergic responses are established. SUMMARY: Supplementation of the maternal diet
      in pregnancy with n-3 PUFA may provide a non-invasive intervention with
      significant potential to prevent the development of allergic and possibly other
      immune-mediated diseases.

PMID- 15864079
TI  - The role of allergen avoidance in the secondary prevention of atopic disorders.
AB  - PURPOSE OF REVIEW: Allergen avoidance is recommended as part of the treatment
      programme of many patients with allergic diseases in Europe and the USA. However,
      clinical trials of allergen avoidance tend to be small and the findings
      inconsistent. Several larger studies have recently been published, making a
      review of the new literature timely. RECENT FINDINGS: There have been two large
      double-blind, placebo-controlled studies on the use of encasings (mattress,
      pillow and duvet) as a single intervention in adults with asthma. In both
      studies, participants in the active and the control group showed an improvement
      in peak flow, but there was no difference between groups over a 12-month period.
      A further smaller study of encasings reported an improvement in peak flow from 1
      week in the active group; this study, however, was only of 9 weeks' duration. In
      children, the use of encasings was associated with a reduction in asthma
      medication usage, but not until 6 months into the study. A multifaceted
      intervention study, with the intervention tailored to the child's sensitization
      status and home environment (including environmental tobacco smoke), resulted in
      significant reductions in emergency room visits and symptoms in the active group.
      SUMMARY: The evidence suggests that interventions in children (either single or
      multifaceted) are associated with a meaningful and sustained improvement in
      asthma control. However, for adults, allergen proof encasings as a single
      intervention cannot be recommended. There is a need for a large-scale
      multifaceted intervention study in adults with asthma.

PMID- 15864080
TI  - Treatment of asthma during pregnancy and perinatal outcomes.
AB  - PURPOSE OF REVIEW: Asthma is the most common, potentially serious medical problem
      to complicate pregnancy. Women with asthma have been shown to be at increased
      risk of complications during pregnancy. Managing asthma during pregnancy is
      unique because the effect of both the illness and the treatment on the developing
      fetus as well as the patient must be considered. This review summarizes the
      recent studies addressing the effects of asthma or asthma medications on
      perinatal outcomes, including the 2004 Asthma and Pregnancy Working Group of the
      National Asthma Education and Prevention Program. RECENT FINDINGS: This review
      summarizes the recent studies addressing the effect of asthma or asthma
      medications on perinatal outcomes. SUMMARY: The prevalence of asthma in pregnant
      women appears to be increasing. Recent evidence supports that pregnant women with
      moderate to severe asthma may have an increased risk of adverse perinatal
      outcomes. The goal of asthma management during pregnancy is to optimize maternal
      and fetal health.

PMID- 15864081
TI  - Transient environmental exposures on the developing immune system: implications
      for allergy and asthma.
AB  - PURPOSE OF REVIEW: Early environmental exposures have been extensively studied as
      potential causes of the observed increase in allergic disease over time.
      Transient fetal or neonatal exposures in particular are of interest in that they
      may occur during critical windows of immune system development. Due to the
      tremendous complexity of variables in early life, as well as the difficulty in
      randomizing many interventions, it is very difficult to properly study these
      exposures. Some progress, however, has been made and some more candidates for
      study may be emerging. Of particular interest are micronutrients, whose ever
      changing use and immunomodulatory capabilities make them prime targets for study.
      RECENT FINDINGS: New risk factors for atopic disease have emerged from the pool
      of early life interventions, such as caesarian section, prolonged labor and
      infant multivitamin supplementation. Data are emerging regarding micronutrient
      status and supplementation and their effects on the developing immune system and
      risk for allergic disease. Clinical trials have yet to demonstrate much causality
      but, in some cases, it is too early to make any judgments. SUMMARY: The gold
      standard of randomized clinical trials has not borne out a number of proposed
      early-life allergic risk factors, while other trials are too incomplete to draw
      any conclusions so far. Properly designed studies for other risk factor
      interventions may still be achievable, provided that there is a proper
      understanding of the interventions, populations and outcomes.

PMID- 15864082
TI  - Short-term clinical outcomes of acute treatment of childhood asthma.
AB  - PURPOSE OF REVIEW: Acute exacerbations of asthma are the leading cause of
      emergency department visits in the pediatric patient. The present review is
      focused on the identification of those factors that may contribute to improving
      the short-term outcome of children after discharge from an emergency department
      visit for acute asthma. RECENT FINDINGS: Several recent studies have documented
      that children treated at the emergency department because of an asthma-related
      event present a high morbidity at 7 and 15 days after discharge, mainly
      associated with symptom persistence, need for rescue bronchodilator medication,
      and absenteeism from school or day nursery. A better control of the disease,
      particularly adequate outpatient follow-up and maintenance treatment with inhaled
      steroids, could improve short-term clinical outcomes. SUMMARY: All efforts of
      emergency room management of children with asthma, identification of severity of
      the current exacerbation episode, and intensive treatment of the acute asthma
      attack have usually been directed at reducing the rates of hospitalization and
      the return for medical care. However, according to reported data on short-term
      morbidity, it is necessary to define therapeutic and follow-up strategies after
      treatment for acute asthma and emergency department discharge. Besides standard
      treatment for an acute asthma exacerbation in a pediatric emergency department,
      action plans should include a review of the maintenance treatment of asthma to
      improve underlying disease control and a strong recommendation for close follow
      up by the primary care pediatrician.

PMID- 15864084
TI  - Genetic and environmental risk factors for the development of food allergy.
AB  - PURPOSE OF REVIEW: To review recent clinical and experimental studies of genetic
      and environmental risk factors for the development of food allergy. RECENT
      FINDINGS: It may be true, although it is yet to be shown, that food allergies in
      early childhood are becoming more common and that the causes are the same as for
      later-developing respiratory allergies. The mother not only transfers 50% of her
      genes to her baby, but she is also the exclusive environment during gestation and
      continues to be a major environmental factor while breast-feeding her infant. Non
      genetic maternal influences increasing the likelihood of food allergy include
      Caesarian section and high maternal age. Allergy to sesame seems to be increasing
      in children. This is possibly a consequence of increased use in processed foods.
      The search for dietary risk factors is not limited to allergenic foods, but may
      include other nutrients, for example excessive intake of vitamins. Two meta
      analyses have seriously questioned the use of special infant formulas for allergy
      prevention. Novel prevention strategies, such as probiotic bacteria, have yet to
      be documented further. SUMMARY: The causes of food allergy are still unknown and
      no particular genes associated particularly with food allergy have been
      identified, although there is a strong association in general between genetic
      susceptibility to food allergy and that to IgE-mediated allergy. There are still
      no measures for general recommendation in order to prevent food allergy and no
      genes have been linked conclusively to disease. Further research concentrating on
      food allergy is obviously needed.

PMID- 15864085
TI  - Primary prevention of food allergy in infants who are at risk.
AB  - PURPOSE OF REVIEW: Allergic diseases represent a major burden of health problems
      in industrialized countries. Though several studies have focused on possible
      preventive measure and strategies much controversy still exists on this topic.
      The aim of this review is to discuss the recent literature on primary prevention
      of food allergy. RECENT FINDINGS: In prospective observational controlled studies
      of high quality of birth cohorts, exclusive breastfeeding for at least 4 months
      combined with introduction of solid foods after 4 months of age is associated
      with a reduced risk of food allergy and atopic dermatitis, particularly in high
      risk infants. When breastfeeding for 4-6 months is not possible or insufficient,
      randomized controlled trials have shown a significant reduction in food allergy
      and atopic dermatitis in high-risk infants fed a documented hypoallergenic
      hydrolysed formula. SUMMARY: Breastfeeding should be encouraged for 4-6 months.
      In high-risk infants a documented hypoallergenic hydrolysed formula is
      recommended if exclusively breastfeeding is not possible for the first 4 months.
      As regards primary prevention of food allergy there is no evidence for preventive
      dietary intervention during neither pregnancy nor lactation. Likewise, preventive
      dietary restrictions after the age of 4-6 months are not scientifically
      documented.

PMID- 15864086
TI  - Food allergy diagnostics: scientific and unproven procedures.
AB  - PURPOSE OF REVIEW: The accurate diagnosis of food allergy is crucial not only for
      the right treatment but also for the avoidance of unnecessary diets. The
      diagnostic work-up of suspected food allergy includes the measurement of food
      specific IgE antibodies using serologic assays, the skin prick test, elimination
      diets and oral provocation tests. In addition, some approaches are either under
      further rigorous investigation (the atopy patch test) or are already in
      widespread use, particularly by practitioners of alternative or complementary
      medicine, but are considered unproven. These diagnostic methods include specific
      IgG to foods, provocation/neutralization testing, kinesiology, cytotoxic tests
      and electrodermal testing. This review covers some of the most common
      scientifically validated and unproven approaches used in the diagnosis of food
      allergy. RECENT FINDINGS: For specific serum IgE and the SPT, decision points
      have been established for some foods, allowing prediction of clinical relevance.
      The APT may be helpful, especially when considered in combination with defined
      levels of specific IgE. In regard to other approaches, most scientific studies do
      refute the usefulness of these approaches. SUMMARY: In most patients, controlled
      oral food challenges remain the gold standard in the diagnostic work-up of
      suspected food allergy. The skin prick test and measurement of specific IgE
      antibodies to food extracts, individual allergens or allergenic peptides are
      helpful in the diagnostic approach. Food-specific IgG continues to be an unproven
      or experimental test. The other alternative and complementary techniques have no
      proven benefit and may endanger patients via misdiagnosis.

PMID- 15864087
TI  - The oral allergy syndrome: improved diagnostic and treatment methods.
AB  - PURPOSE OF REVIEW: The aim of this article is to review recent clinical and
      molecular findings related to the oral allergy syndrome in order to define its
      relevance in the field of food allergy, describe current diagnostic approaches
      and discuss attempts to use specific immunotherapy for treatment. RECENT
      FINDINGS: New allergenic sources causing the oral allergy syndrome have been
      reported. Their allergenic molecules have been identified. In most of those
      studies oral allergy syndrome is reported as a clinical manifestation among more
      severe ones. Some of the molecules generally considered not to be at risk for
      severe reactions have been demonstrated to pose a threat for inducing generalized
      reactions. Some studies tried to assess the usefulness of immunotherapy with
      birch pollen extract by either subcutaneous or sublingual routes for the
      treatment of associated food allergies. In most of the cases, a well defined
      study design and a molecular approach at different study levels are lacking and
      thus the value of the obtained results is limited. To date, no final conclusion
      can be drawn on the basis of reported results. SUMMARY: The knowledge about the
      highly prevalent phenomenon of oral allergy syndrome is still incomplete, in
      respect to both, epidemiology and foods inducing symptoms. It is very important
      to reach consensus on several aspects of this food-induced allergic disease.
      Further studies are required to highlight whether immunotherapy using co
      recognized inhalant allergens is an effective way of curative treatment, or if co
      treatment with purified pollen-related food allergens will be required to obtain
      a long-lasting effect.

PMID- 15864088
TI  - Nonspecific lipid-transfer proteins in plant foods and pollens: an important
      allergen class.
AB  - PURPOSE OF REVIEW: Here we focus our attention on the structural stability and
      physicochemical properties of plant nonspecific lipid-transfer proteins (nsLTPs)
      as keys to their allergenicity. We further present the current opinions on the
      route of sensitization and include the latest additions to the nsLTP allergen
      family. RECENT FINDINGS: Plant nsLTPs are small cysteine-rich lipid-binding
      proteins that play a key role in plant resistance to biotic and abiotic stress.
      Besides their relevance for plant-pathogen interactions, nsLTPs have attracted
      interest as true food allergens which are of high importance to atopics in
      Mediterranean countries. It is now becoming clear that their molecular properties
      such as the remarkable stability to proteolysis and thermal denaturation are
      intrinsically linked to their allergenicity. These properties also facilitate
      sensitization via the gastrointestinal tract which allows these molecules to act
      as allergens independently of prior exposure to pollen. In addition, a group of
      allergenic pollen nsLTPs exists which seem to be only partially linked to the
      food nsLTPs by cross-reactivity. SUMMARY: Research into the family of nsLTPs will
      continue to provide insights about the particular molecular properties that make
      an nsLTP an allergen and how primary sensitization occurs.

PMID- 15864089
TI  - Anisakis simplex: sensitization and clinical allergy.
AB  - PURPOSE OF REVIEW: Whereas gastric anisakiasis has been known for several
      decades, the implications of Anisakis simplex-related allergic disorders had not
      been thoroughly studied until the late 1990s. This article reviews recent
      knowledge of allergic disorders ascribed to A. simplex contact or parasitism.
      RECENT FINDINGS: Gastroallergic anisakiasis describes an acute hypersensitivity
      reaction emerging in the context of an acute parasitism by the nematode A.
      simplex. But other frequent allergic disorders like chronic urticaria are now
      being studied for a possible relationship with A. simplex parasitism. In recent
      investigations, non-IgE mediated mechanisms, such as the involvement of other
      immunoglobulin isotypes (IgG4), or non-immunological events are discussed.
      SUMMARY: The experience of the last several years shows that allergic
      hypersensitivity symptoms in gastroallergic anisakiasis are clinical events
      accompanying a wide range of immunologic reactions as a host response against a
      ubiquitous parasite. The discussed and reviewed studies should motivate
      allergists around the world to search for this entity. Further studies in the
      field of allergy could benefit from the experience of this peculiar food-related
      disorder.

PMID- 15864090
TI  - Beyond allergen avoidance: update on developing therapies for peanut allergy.
AB  - PURPOSE OF REVIEW: Food allergy has emerged as a significant health problem.
      Peanut allergy is a major cause of food-induced fatal and near fatal anaphylactic
      reactions, and the incidence in children is increasing. Attempts to manage peanut
      allergy by strict avoidance are often unsuccessful. The purpose of this review is
      to highlight the most promising novel approaches for treating peanut allergy
      beyond allergen avoidance. RECENT FINDINGS: In the past 5 years much effort has
      been devoted to developing a treatment for peanut allergy. A recent clinical
      trial showed that monthly injections of humanized recombinant anti-IgE antibodies
      increased the threshold for allergic responses of peanut-sensitive individuals,
      at least to small amounts of peanut protein. However, this treatment cannot cure
      peanut allergy, and continuous monthly injections are necessary to maintain
      protection. Developing new therapies for the treatment of peanut allergy is
      essential. In reviewing publications between 2003 and 2005, several novel
      therapeutic approaches, tested in the murine model of peanut anaphylaxis appeared
      promising. Immunotherapy with engineered recombinant peanut protein and bacterial
      adjuvant significantly protected peanut allergic mice from anaphylaxis. It was
      also found that a Chinese herbal medicine formula called Food Allergy Herbal
      Formula-2 completely blocked anaphylaxis up to 5 weeks following therapy. These
      potent therapeutic effects are associated with immunoregulation of Th1 and Th2
      responses. SUMMARY: Although there is no effective and safe therapy for food
      allergy, many novel approaches are under investigation. Some of these approaches
      may provide allergists with effective treatments in the near future.

PMID- 15864091
TI  - Emergency management of food allergy: systems perspective.
AB  - PURPOSE OF REVIEW: Food-related allergic reactions are the leading cause of
      anaphylactic reactions treated in the emergency department, accounting for
      approximately 30 000 emergency department visits each year, and 150-200 deaths.
      The purpose of this review is to examine current research on food-related
      allergic reactions in the emergency department, and to provide suggestions for
      how to improve emergency department management. RECENT FINDINGS: There are few
      published studies since March 2003 that examine the emergency management of food
      related allergic reactions. Earlier studies found that few patients treated in
      the emergency department for this problem received health education (e.g.,
      instructions to avoid offending food allergens), a prescription for self
      injectable epinephrine, or referral to an allergy specialist at emergency
      department discharge. A recent multicenter study by our research group
      demonstrated that emergency department patients with food-related allergic
      reactions continue to receive care discordant from guidelines for the emergency
      management of allergic disorders and anaphylaxis. Discordance is low even among
      those with multisystem complaints consistent with anaphylaxis. SUMMARY:
      Concordance with suggested guidelines for the treatment of severe acute allergic
      reactions remains poor. Development of a simple, clinical definition of food
      related anaphylaxis is needed to improve emergency management. Dissemination of
      guidelines for the emergency management of anaphylaxis, and creation of systems
      to implement these guidelines, are essential for the improved treatment of food
      related allergic reaction and anaphylaxis in the emergency department.

PMID- 15864092
TI  - Bibliography. Current world literature. Outcome measures.

PMID- 15864094
TI  - Innate immunity to bacterial infection: toll receptors, professional phagocytes,
      intra-phagosomal killing, defensins and cytoplasmic muramyl dipeptide sensors.

PMID- 15864095
TI  - Respiratory syncytial virus pneumonia: mechanisms of inflammation and prolonged
      airway hyperresponsiveness.
AB  - PURPOSE OF REVIEW: Respiratory syncytial virus is the leading viral pathogen
      associated with lower respiratory tract infection in young children worldwide.
      The pathogenesis of acute bronchiolitis and the mechanisms by which the virus
      induces long-term airway disease remain to be elucidated. This review highlights
      new findings reported in the English-language medical literature from January
      2004 to January 2005. RECENT FINDINGS: Several studies have confirmed a strong
      association between respiratory syncytial virus infection in infancy and an
      increased risk for recurrent wheezing. Evidence indicates that the exaggerated
      immune response and abnormal neurogenic mechanisms induced by the virus play a
      significant role in the pathogenesis of the disease. Different genetic and immune
      markers have been correlated with acute disease severity and with increased risk
      of long-term pulmonary abnormalities. Recently, the application of real time
      polymerase chain reaction has demonstrated the persistence of respiratory
      syncytial virus RNA in the lungs of infected mice for months after inoculation.
      This unexpected observation has stimulated discussions as to whether the long
      term presence of the virus could contribute to the long-term airway disease
      observed in children after respiratory syncytial virus lower respiratory tract
      infection. SUMMARY: Despite almost half a century of active research into the
      pathogenesis of respiratory syncytial virus-induced acute and chronic airway
      disease, many questions remain unresolved. Studies in animal models demonstrate
      that interventions reducing viral replication resulted in improvement of acute
      disease severity and long-term pulmonary abnormalities. The stage is ready for
      clinical studies to determine whether preventing or delaying the primary
      infection could reduce the incidence of recurrent wheezing in children.

PMID- 15864096
TI  - The antiphospholipid syndrome: clinical characteristics, laboratory features and
      pathogenesis.
AB  - PURPOSE OF REVIEW: The antiphospholipid syndrome is characterized by the
      paradoxical linkage between thrombosis in vivo and prolongation of clotting times
      in vitro. Recent reports that are discussed in this overview have taught us that
      this inconsistency is not so incomprehensible after all. RECENT FINDINGS: Only a
      subpopulation of the heterogeneous population of antiphospholipid antibodies is
      pathogenic. New hypotheses have been proposed to explain the thrombotic tendency
      in this syndrome. In contrast to what is generally thought, it seems that the
      increased risk of thrombotic complication is independent of chronic vascular
      disease. SUMMARY: The latest developments could make it possible to define
      patients with the syndrome unambiguously. This is absolutely necessary to
      facilitate studies designed to test the current hypotheses on the pathophysiology
      of antiphospholipid syndrome.

PMID- 15864097
TI  - Recent developments in tuberculosis vaccines.
AB  - PURPOSE OF REVIEW: The aim is to review findings related to the use of Bacille
      Calmette-Guerin (BCG) vaccine, focusing on its limitations and benefits in
      controlling tuberculosis (TB). Some new TB vaccines, which have entered or are
      expected to enter clinical trials, are highlighted. RECENT FINDINGS: BCG is
      currently the only available vaccine against TB, and is widely administered
      within the World Health Organization Expanded Programme for Immunization. Several
      trials have shown that the protective efficacy of BCG varies between different
      populations. Recently, a 60-year follow-up study of American Indians reported the
      long-term efficacy of BCG to be 52%. The reasons for the low efficacy of the BCG
      vaccine may be generic differences in the BCG strains, differences in
      immunological properties of study populations or exposure to environmental
      factors such as mycobacteria. The low efficacy of the BCG vaccine has encouraged
      the search for a new vaccine. Among new vaccine candidates are live attenuated
      Mycobacterium tuberculosis vaccines, recombinant BCG, DNA vaccines, subunit
      vaccines and fusion proteins with novel adjuvants and delivery systems. SUMMARY:
      Today, most of the world's population is vaccinated with BCG. It is generally
      accepted that BCG protects against childhood TB but this immunity wanes with age,
      resulting in no or insufficient protection against TB. Using modern techniques,
      several research groups have developed more than 200 new vaccine candidates. Some
      of these vaccines are now in clinical trials. The clinical evaluation of these
      new vaccines should be designed to cover a heterogeneous population with great
      variation in immune responses.

PMID- 15864098
TI  - Immunity to the ehrlichiae: new tools and recent developments.
AB  - PURPOSE OF REVIEW: Discusses recent developments in the study of immunity and
      host defense against the monocytic ehrlichiae in 2003 and 2004. The review does
      not address anaplasmoses, as the anaplasmae were recently re-classified into the
      genus Anaplasma, and are distinct in cell tropism from the ehrlichiae. RECENT
      FINDINGS: The features of the immune responses against these emerging Gram
      negative obligate intracellular pathogens are only beginning to be understood.
      Important advances in our ability to study host defense include the development
      of new experimental mouse models. Recent studies have defined possible mechanisms
      of innate immune subversion in human monocytes, as well as roles for lymphocyte
      subsets and type I cytokines during mouse infection. Other studies in the mouse
      suggest that cytokine production by CD8 T cells may contribute to
      immunopathology. New data also support a role for humoral immunity during host
      defense against these intracellular pathogens. SUMMARY: The use of new animal
      models will facilitate research of the mechanisms of innate, adaptive, and
      pathological immune responses, and will enhance our understanding of human
      immunity to the ehrlichiae as well as to other pathogenic intracellular bacteria.

PMID- 15864099
TI  - The role of type-specific antibodies in colonization and infection by
      Helicobacter pylori.
AB  - PURPOSE OF REVIEW: Helicobacter pylori is a Gram-negative spiral bacterium that
      colonizes the stomach of humans, causing gastritis, peptic ulcer disease, or
      gastric cancer. H. pylori infection accounts for a high percentage of mortality
      and morbidity rates in developing as well as developed countries. H. pylori
      bacteria reside in the mucus layer covering the gastric epithelium, and therefore
      the type of protective measures that could confer resistance appear to be
      limited. Although H. pylori infection stimulates strong local and systemic
      specific IgA and IgG antibody production, the influence of antibodies on
      bacterial colonization and gastric inflammation is still controversial. RECENT
      FINDINGS: Recent studies in experimental animal models have indicated a non
      essential role of specific antibodies for host resistance against H. pylori
      infection. Recent data show that protection is mediated by T cells, CD4 T helper
      type 1 cells, in particular. Antibodies are not only dispensable for protection,
      but they impair both the elimination of bacteria and the development of
      gastritis. This effect appears to be IgA-dependent and is not a function of
      specific IgM or IgG antibodies. SUMMARY: This review highlights the recent
      advances in our understanding of how antibodies may influence the development of
      gastric inflammation and bacterial colonization. Such information can
      significantly increase our basic knowledge of immune regulation and protection
      against H. pylori infection, but can also indicate new strategies for vaccine
      development.

PMID- 15864100
TI  - Measles.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize important papers
      concerning measles disease and measles-containing vaccines published in 2004.
      RECENT FINDINGS: Endemic measles has been successfully controlled in the Americas
      and, to a lesser extent, in Europe. This has been achieved with a high uptake of
      two doses of a measles-containing vaccine. Even in industrialized countries,
      where vaccine uptake is poor, for example Japan, the disease is still a
      significant cause of morbidity and mortality. Vaccine failure is predominantly
      due to primary vaccine failure, which may, in part, be genetic in origin and
      related to HLA type. Measles-containing vaccines have been shown to be associated
      with febrile convulsions, but there is no strong evidence of a link with atopy.
      There is considerable evidence that there is no causal relationship with autistic
      disorders. In spite of this, many parents and some professionals have concerns
      about the safety of the vaccines, which may lead to their underuse. SUMMARY: It
      is possible to eliminate measles with a high uptake of two doses of measles
      containing vaccine, but concerns about safety persist and need to be tackled.
      More research is required into how to do this effectively and also to elucidate
      the causes of vaccine failure.

PMID- 15864101
TI  - Chickenpox.
AB  - PURPOSE OF REVIEW: Varicella-zoster virus (VZV) remains a public health issue
      around the globe despite the availability of a live attenuated vaccine and
      several highly active antiviral agents. A program of universal infant vaccination
      against varicella was introduced in the US almost 10 years ago. Epidemiological
      data continue to accumulate that will inform decision-making on vaccine use
      elsewhere. These findings, together with relevant advances in VZV virology, form
      the substance of this review. RECENT FINDINGS: Understanding of the pathogenesis
      of varicella has significantly advanced with the demonstration that the cation
      independent mannose 6-phosphate receptor is critical to both entry and egress of
      enveloped VZV. While our knowledge of intervening events remains sketchy, the
      future study of VZV will be facilitated by the recent successful cloning of the
      VZV genome into a bacterial artificial chromosome. Models of latency and
      reactivation are also being developed, which may help us to understand the
      epidemiology of herpes zoster in vaccinated populations. Continued evidence of
      decline in the incidence of varicella, associated hospitalizations and deaths
      suggests that the vaccine as used in the US is highly effective. However, rates
      of breakthrough disease are significant and sufficient to sustain outbreaks, even
      among highly vaccinated populations. This is so despite the generally reduced
      infectiousness of varicella occurring in vaccinated individuals. There is some
      evidence of attrition of the immune response over time following immunization in
      a small proportion of vaccinees. SUMMARY: Our ability to prevent and treat
      varicella still outstrips our knowledge of pathogenetic and immune mechanisms.
      Further clinical advances are likely to arise from growing understanding of VZV
      biology.

PMID- 15864102
TI  - Cytomegalovirus.
AB  - PURPOSE OF REVIEW: To identify recent developments in the management of
      congenital cytomegalovirus infection which continues to exact a heavy toll on the
      developing central nervous system. RECENT FINDINGS: A major advance is the
      publication of a randomized controlled trial showing that hearing loss is
      significantly decreased by ganciclovir. This treatment should now be offered to
      all neonates who would have met the eligibility criteria of the trial, that is
      proven congenital infection with central nervous system involvement when
      treatment is begun within 1 month of birth. A second major advance is the use of
      stored dried blood spots to detect cytomegalovirus DNA and so differentiate
      congenital infection from perinatal infection. This approach has the potential to
      diagnose a proportion of cases of hearing loss and mental retardation which are
      currently labelled idiopathic. A third major advance is the clinical evaluation
      of vaccines against cytomegalovirus. Experiments with guinea pig cytomegalovirus
      show reduced fetal mortality and congenital infection among dams given vaccines
      containing the glycoprotein B of the virus. A different vaccine glycoprotein B
      construct has been shown to be immunogenic and well tolerated in healthy adult
      and paediatric humans. Recent reviews from the Institute of Medicine and the
      National Vaccine Advisory Committee emphasize the financial and humanitarian
      justifications for developing cytomegalovirus vaccines as a high priority.
      SUMMARY: Substantial progress has recently been made in diagnosis and treatment.
      If additional financial support were to be made available to evaluate existing
      vaccine candidates in controlled clinical trials, congenital cytomegalovirus
      could potentially become a vaccine-preventable disease.

PMID- 15864103
TI  - Human herpesviruses-6 and -7 infections.
AB  - PURPOSE OF REVIEW: To summarize the biology and clinical consequences of
      infection with the closely related human herpesviruses-6 and -7 (HHV-6/7) in
      children. RECENT FINDINGS: Over the last year there has been a paucity of
      paediatric publications on HHV-6 and only two studies focused on HHV-7. Steady
      progress has been made regarding the biology and clinical consequences of HHV-6
      infection whereas the effect of HHV-7 infection remains a neglected topic.
      However, both viruses have been shown to contribute significantly and equally to
      the burden of disease in young children with suspected encephalitis or severe
      convulsions with fever. There continues to be uncertainty as to the effects of
      HHV-6 infection after stem cell transplant, although there is general agreement
      that it contributes to encephalitis. In contrast, HHV-7 seems to have little
      clinical impact after stem cell transplant, although central nervous system
      infection and disease have recently been reported in children. Understanding the
      contribution of chromosomal integration and inheritance of both HHV-6 variants A
      and B (HHV-6A/B) and their effect on diagnosis is emerging. SUMMARY: There is an
      urgent need for more research on HHV-6 and -7 in children, particularly in
      relation to chromosomal integration of HHV-6A and B, and clinical consequences of
      HHV-7 infection.

PMID- 15864104
TI  - Children with HIV: improved mortality and morbidity with combination
      antiretroviral therapy.
AB  - PURPOSE OF REVIEW: Advances in the management of children with vertical HIV-1
      infection in the developing and developed worlds are discussed in reference to
      literature published in 2003/4. Studies in mother-to-child transmission are
      beyond the scope of this review. RECENT FINDINGS: Improvements in mortality and
      morbidity from HIV-1 infection following combination antiretroviral therapy are
      extremely encouraging. There is an increase in the understanding of the immune
      response to HIV-1 in infants and children and a possible future role for
      immunomodulatory therapies. Preliminary data are available on the timing of
      initiation of antiretroviral therapy, the optimization of drug combinations and
      the clinical interpretation of genotypic resistance testing and therapeutic drug
      monitoring. Evidence is emerging that early antiretroviral therapy can protect
      the central nervous system in infants. In resource-limited settings, mortality
      and morbidity remain extremely high but low-cost health interventions such as
      prophylactic co-trimoxazole can reduce mortality prior to the expansion of
      antiretroviral therapy programmes. SUMMARY: Further randomized controlled trials
      assessing antiretroviral therapy combinations with a sustained
      virological/immunological response with minimal toxicities are required. The
      roles of therapeutic drug monitoring and resistance testing require further
      elucidation. The expansion of antiretroviral therapy programmes is essential for
      children with HIV living in resource-limited settings.

PMID- 15864106
TI  - Bibliography. Current world literature. Pathogenesis and immune response.

PMID- 15864105
TI  - Hepatitis B virus and hepatitis C virus infections in children.
AB  - PURPOSE OF REVIEW: To analyse the most relevant recent information on efficacy,
      duration and coverage of anti-hepatitis B virus vaccination; correlates of mother
      to-child hepatitis C virus transmission; the natural history and outcomes of
      hepatitis B and C virus infections in children; the efficacy and safety of
      specific therapies. RECENT FINDINGS: Insufficient hepatitis B virus vaccine
      coverage and incomplete or delayed vaccine cycles need improvement in many
      countries. Hepatitis B virus mutants may explain some fulminant hepatitis in
      perinatally infected infants and vaccine failures. No interventions to prevent
      vertical hepatitis C virus transmission have been identified. Spontaneous
      clearance of hepatitis B is lower in children than in adults, while the rates
      appear to be similar for hepatitis C. The disease progression is slower for both
      infections in childhood. Several studies support the efficacy and safety of
      interferons and lamivudine in chronic hepatitis B or of interferons and ribavirin
      in chronic hepatitis C in children, but the optimal therapy remains unclear.
      SUMMARY: There are doubts as to the long-term persistence of anti-hepatitis B
      immunization in low-endemicity areas. Routine hepatitis C virus testing in
      pregnancy is not recommended as there are no available prophylactic measures.
      Although hepatitis B and C virus infections are usually asymptomatic or with mild
      manifestations in childhood, concerns around their long-term clinical impact
      suggest the need for early treatment. Children should preferably be treated in
      the context of targeted trials for a better understanding of the efficacy and
      tolerance of drugs currently used in adults.

PMID- 15864109
TI  - Sepsis in the immunocompromised child: the least studied with the most to gain.

PMID- 15864110
TI  - Weight gain with antipsychotic drugs: the role of the 5-HT2C receptor (HTR2C) and
      other genes.

PMID- 15864111
TI  - Polymorphisms of the 5-HT2C receptor and leptin genes are associated with
      antipsychotic drug-induced weight gain in Caucasian subjects with a first-episode
      psychosis.
AB  - OBJECTIVES: Weight gain, leading to further morbidity and poor treatment
      adherence, is a common consequence of treatment with antipsychotic drugs. Two
      recent studies in the same cohort of Chinese Han subjects have shown that
      polymorphisms of the promoter regions of both the serotonin 5-hydroxytryptamine
      2C (5-HT2C) receptor and the leptin genes, are associated with antipsychotic
      induced weight gain over 10 weeks. We have investigated whether these effects
      remain true in a Caucasian population and following longer term treatment.
      METHODS: Seventy-three Spanish caucasian patients with a first-episode psychosis
      and initially drug-naive were genotyped for the 5-HT2C receptor -759C/T and
      leptin -2548A/G polymorphisms. Body mass index and plasma leptin levels were
      monitored after 6 weeks, 3 months and 9 months of antipsychotic treatment.
      RESULTS: Patients with the -759T variant allele showed significantly less weight
      gain than those without this allele. This effect held true in the smaller group
      of patients receiving olanzapine. The -2548 leptin polymorphism was not
      associated with short-term (6 week and 3 month) weight increases but did show
      significant association with 9-month antipsychotic-induced weight gain. The 5
      HT2C -759 genotype was significantly associated with pre-treatment plasma leptin
      levels. CONCLUSIONS: These findings confirm the importance of two genetic factors
      associated with long-term antipsychotic-induced weight increases in
      schizophrenia, and implicate a role for leptin in the 5-HT receptor-mediated
      weight regulation.

PMID- 15864112
TI  - Functional analysis of polymorphisms in the organic anion transporter, SLC22A6
      (OAT1).
AB  - OBJECTIVES: The organic anion transporter, OAT1 (SLC22A6), plays a role in the
      renal elimination of many drugs and environmental toxins. The goal of this study
      was to identify and functionally characterize OAT1 variants as a first step
      towards understanding whether genetic variation in OAT1 may contribute to
      interindividual differences in renal elimination of xenobiotics. METHODS: As part
      of a larger study, 276 DNA samples from an ethnically diverse population were
      screened and 12 coding region variants of OAT1 were identified. The non
      synonymous variants were then constructed and characterized in Xenopus laevis
      oocytes. A small family-based clinical study was conducted to determine the renal
      elimination of a model OAT1 substrate, adefovir (an antiviral agent) in human
      subjects who possessed a non-functional variant, OAT1-R454Q. RESULTS: Six non
      synonymous variants were identified; two (OAT1-R50 H and OAT1-R293W) were present
      at > or = 1% in at least one ethnic population. These two variants exhibited
      normal uptake of p-aminohippurate, ochratoxin A and methotrexate assayed in X.
      laevis oocytes. One variant, OAT1-R454Q, was non-functional with respect to the
      above substrates. In the clinical study, there was no significant decrease in the
      renal secretory clearance of adefovir in family members heterozygous for OAT1
      454Q in comparison to those with the reference transporter, OAT1-454R.
      CONCLUSIONS: These data indicate that the coding region of OAT1 has low genetic
      and functional diversity and suggest that coding region variants of OAT1 may not
      contribute substantially to interindividual differences in renal elimination of
      xenobiotics.

PMID- 15864113
TI  - Influence of microsomal triglyceride transfer protein promoter polymorphism -493
      GT on fasting plasma triglyceride values and interaction with treatment response
      to atorvastatin in subjects with heterozygous familial hypercholesterolaemia.
AB  - Familial hypercholesterolaemia (FH) is an autosomal dominant disease
      characterized by elevated levels of low-density lipoprotein-cholesterol (LDL-C).
      Phenotypic expression is highly variable, being influenced by diet, age, gender,
      body mass index, apolipoprotein E genotype and type of LDL-receptor gene
      mutation. Microsomal triglyceride (TG) transfer protein (MTP) is a protein
      involved in lipid metabolism. Polymorphism MTP -493 GT has been shown to modulate
      lipid levels in several populations. To analyse the effect of this polymorphism
      in the lipid phenotype expression of FH and treatment response, we studied a
      sample of 222 Spanish FH patients, of whom 147 were studied before and after
      treatment with 20 mg of atorvastatin daily during 6 weeks. The variant was
      analysed by polymerase chain reaction amplification and single-strand
      confirmation polymorphism. Treatment reduced LDL-C, total cholesterol and TGs.
      Baseline fasting TGs and very-low-density lipoprotein cholesterol levels were
      lower in female T allele carriers (TG: 111+/-51 mg/dl GG, 89+/-35 mg/dl GT, 83+/
      26 mg/dl TT, P=0.022; very-low-density lipoprotein cholesterol: 24+/-13 mg/dl GG,
      16+/-5 mg/dl GT, 17+/-5 mg/dl TT, P=0.018). Triglyceride response to atorvastatin
      was modulated by this polymorphism in men (P=0.009), but not in women, although
      differences between genotypes were maintained after treatment. In conclusion, the
      MTP -493 GT polymorphism modulates pre- and post-treatment plasma TG values of FH
      in Spanish subjects in a gender-specific way. Other environmental and genetic
      factors likely also modulate this response.

PMID- 15864114
TI  - Genetic and environmental factors affecting the response to statin therapy in
      patients with molecularly defined familial hypercholesterolaemia.
AB  - Familial hypercholesterolaemia (FH) is the most common inherited metabolic
      disease characterized by elevated serum levels of low-density lipoprotein
      cholesterol (LDL-C) and ischaemic heart disease early in life. Early diagnosis
      and treatment are essential to prevent premature atherosclerosis in FH patients.
      The aim of our study was the evaluation of the effects of genetic [class of the
      LDL receptor (LDLR) gene mutation, apolipoprotein (apo)E, apoA-IV and cholesterol
      ester transfer protein gene polymorphisms] and environmental factors (age, sex,
      smoking habit and body mass index) on the lipid-lowering response to statin
      therapy in patients with molecularly defined FH. Atorvastatin 20 mg/day was
      prescribed in 49 patients with heterozygous FH. The lipid profile was examined
      before and after 12 weeks of therapy. Statin therapy resulted in a decrease of
      37% and 36% in LDL-C and apoB levels, respectively. The study population was then
      divided into 2 groups according to the class of the LDLR mutation [patients
      sharing a class V mutation (the G1775A mutation, n=21) and patients sharing class
      II mutations (the G1646A and the C858A mutations, n=28)]. In both groups, the
      percentage decrement in LDL-C and apoB levels were correlated with the initial
      LDL-C and apoB levels, respectively. The class of the LDLR mutation affected the
      LDL-C and apoB-lowering response of heterozygous FH patients to statin therapy.
      In detail, heterozygotes sharing a class V mutation of the LDLR showed a higher
      percentage decrement in LDL-C and apoB levels after atorvastatin administration
      compared to patients sharing class II mutations (49+/-9% versus 34+/-9%, P=0.001
      for LDL-C and 42+/-16% versus 35+/-20%, P=0.001 for apoB). The influence of the
      classes of the LDLR gene mutations on the change of LDL-C and apoB levels to
      atorvastatin was still significant in a multivariate analysis. None of the other
      genetic and environmental factors studied affected the lipid-lowering response to
      atorvastatin therapy in patients with heterozygous FH in a multivariate analysis.
      Our data indicate that the class of the LDLR gene mutation affects the LDL-C and
      apoB-lowering response of heterozygous FH patients to statin therapy.
      Specifically, patients with a class V mutation exhibit higher percentage decrease
      in LDL-C and apoB levels after statin therapy compared to patients sharing class
      II mutations.

PMID- 15864115
TI  - Beta1-adrenergic receptor polymorphisms and left ventricular remodeling changes
      in response to beta-blocker therapy.
AB  - OBJECTIVE: Large variability exists in the improvement in left ventricular (LV)
      function from beta-blocker treatment. We hypothesized that polymorphisms at codon
      389 (Arg389Gly) and 49 (Ser49Gly) in the beta1-adrenergic receptor (AR) gene were
      associated with LV reverse remodeling changes in response to beta-blocker therapy
      among heart failure patients. METHODS: We prospectively enrolled 61 beta-blocker
      naive patients with systolic heart failure. Patients underwent baseline
      echocardiography followed by metoprolol CR/XL. The dose was doubled on a biweekly
      basis up to 200 mg/day or attainment of maximum tolerated dose. Echocardiography
      was repeated after the patient received the target or highest tolerated dose for
      3 months. RESULTS: Among patients with the Arg389Arg genotype, ejection fraction
      (EF) increased from 23+/-5 to 29+/-10 (P=0.008). Gly389 carriers did not
      demonstrate any significant change in EF (22+/-9 to 23+/-11; P=0.45). There was a
      significant between-group difference in EF by genotype (P=0.04). The Arg389Arg
      genotype was also associated with significantly greater reductions in LV end
      diastolic and end-systolic diameters compared to Gly389 carriers. Patients with
      the Gly49 variant also had a significantly greater reduction in LV end-diastolic
      diameter compared to Ser49 homozygotes. Multiple regression analysis modeling
      revealed that the codon 389 polymorphism was a significant predictor of an
      improvement in EF and both codon 49 and 389 polymorphisms were significant
      predictors of final LV end-diastolic diameter. CONCLUSIONS: Heart failure
      patients with the Arg389Arg genotype and Gly49 carriers had greater improvements
      in LV remodeling from beta-blocker treatment.

PMID- 15864116
TI  - Preferred mexiletine block of human sodium channels with IVS4 mutations and its
      pH-dependence.
AB  - The effects of extracellular pH (6.2, 7.4 and 8.2) and 0.1 mM mexiletine, a
      channel blocker of the lidocaine type, are studied on two mutations of the fourth
      voltage sensor of the Nav1.4 sodium channel, R1448H/C. The fast inactivated
      channel state to which mexiletine preferentially binds is destabilized by the
      mutations. By contrast to the expected low response of R1448H/C carriers,
      mexiletine is particularly effective in preventing exercise-induced stiffness and
      paralysis from which these patients suffer. Our measurements performed in the
      whole-cell mode on stably transfected HEK cells show for the first time that the
      mutations strikingly accelerate closed-state inactivation and, as steady-state
      fast inactivation is shifted to more negative potentials, stabilize the fast
      inactivated channel state in the potential range around the resting potential. At
      pH 7.4 and 8.2, the phasic mexiletine block is larger for R1448C (55%) and R1448H
      (47%) than for wild-type channels (31%) due to slowed recovery from block (tau is
      approximately 520 ms for R1448C versus 270 ms for wild-type at pH 7.4) although
      the recovery from inactivation is slightly faster for the mutants (tau is
      approximately 1.9 ms for R1448C versus 3.8 ms for wild-type at pH 7.4). At pH
      6.2, recovery from block is relatively fast (tau is approximately 35 ms for
      R1448H/C and 14 ms for wild-type) and thus shows no use-dependence. We conclude
      that enhanced closed-state inactivation expands the concept of a mutation-induced
      uncoupling of channel inactivation from activation to a new potential range and
      that the higher mexiletine efficacy in R1448H/C carriers compared to other
      myotonic patients offers a pharmacogenetic strategy for mutation-specific
      treatment.

PMID- 15864117
TI  - Haplotype and functional analysis of four flavin-containing monooxygenase isoform
      2 (FMO2) polymorphisms in Hispanics.
AB  - OBJECTIVES: Previous work defined two flavin-containing monooxygenase 2 (FMO2)
      alleles. The major allele, FMO2*2 (g.23,238C>T), encodes truncated inactive
      protein (p.X472) whereas the minor allele, FMO2*1, present in African- and
      Hispanic-American populations, encodes active protein (p.Q472). Recently, four
      common (27 to 51% incidence) FMO2 single nucleotide polymorphisms (SNPs) were
      detected in African-Americans (N=50); they encode the following protein variants:
      p.71Ddup, p.V113fs, p.S195L and p.N413 K. Our objectives were to: (1) determine
      the incidence of these SNPs in 29 Hispanic individuals previously genotyped as
      g.23,238C (p.Q472) and 124 previously genotyped as homozygous g.23,238 T
      (p.X472); (2) determine FMO2 haplotypes in this population; and (3) assess the
      functional impact of SNPs in expressed proteins. METHODS: SNPs were detected via
      allele-specific oligonucleotide amplification coupled with real-time or
      electrophoretic product detection, or single strand conformation polymorphism.
      RESULTS: The g.7,700_7,702dupGAC SNP (p.71Ddup) was absent. The remaining SNPs
      were present but, except for g.13,732C>T (p.S195L), were less common in the
      current Hispanic study population versus the previously described African
      Americans. Only expressed p.N413 K was as active as p.Q472, as determined by
      methimazole- and ethylenethiourea-dependent oxidation. Haplotype determination
      demonstrated that the g.10,951delG (p.V113fs), g.13,732C>T (p.S195L) and
      g.22,060T>G (p.N413 K) variants segregated with g.23,238C>T (p.X472).
      CONCLUSIONS: SNPs would not alter FMO2 activity in individuals possessing at
      least one FMO2*1 allele. It is likely that these SNPs will segregate similarly in
      African-American populations. Therefore, estimates that 26% of African-Americans
      and 2-7% of Hispanic-Americans have at least one FMO2*1 allele should closely
      reflect the percentages producing active FMO2 protein.

PMID- 15864118
TI  - The naturally occurring Arg219Leu variant of the human 5-HT1A receptor:
      impairment of signal transduction.
AB  - The present study in transfected HEK293 cells aimed to investigate whether the
      pharmacological and/or transductional properties of the naturally occurring
      Arg219Leu variant (VAR) in the third intracellular loop of the h5-HT1A receptor
      differ from those of the wild-type receptor. Binding of [3H]8-hydroxy-2-(di-n
      propylamino)tetraline ([H]8-OH-DPAT) and of [35S]GTPgammaS to membranes, as well
      as inhibition of forskolin-stimulated [3H]cAMP formation by 5-HT receptor
      agonists in whole cells, were estimated. The VAR and wild-type h5-HT1A receptors
      were found to be expressed at virtually identical densities. The VAR and wild
      type receptors did also not differ with respect to the potencies of 5-HT receptor
      agonists and antagonists in inhibiting [3H]8-OH-DPAT binding. The ability of 5-HT
      to stimulate [35S]GTPgammaS binding (a measure of G protein coupling) to the VAR
      receptor and of the agonists 5-HT, buspirone and urapidil to inhibit forskolin
      stimulated cAMP accumulation in HEK293 cells expressing the VAR receptor was
      decreased by 60-90%. In conclusion, the Arg219Leu variation of the human 5-HT1A
      receptor does not change the binding properties, but is associated with a drastic
      impairment of signal transduction. In patients carrying this variation,
      disturbances of 5-HT1A receptor-mediated functions and diminished responses to
      drugs acting via this receptor may occur.

PMID- 15864119
TI  - Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and
      toxicity of efavirenz and nevirapine in HIV-infected patients.
AB  - BACKGROUND: Efavirenz (EFV) and nevirapine (NVP) are metabolized by cytochrome
      P450 2B6 (CYP2B6). Allele 516 G>T (Gln172His) is associated with diminished
      activity of this isoenzyme, and may lead to differences in drug exposure.
      METHODS: We evaluated this allele as a pharmacogenetic marker of EFV and NVP
      pharmacokinetics and EFV toxicity in 167 participants receiving EFV and 59
      receiving NVP recruited within the genetics project of the Swiss HIV Cohort
      Study. Drug concentrations were measured in plasma and in peripheral blood
      mononuclear cells (PBMCs) from the same sample. Neuropsychological toxicity of
      EFV (sleep disorders, mood disorders, fatigue) was assessed using a standardized
      questionnaire. RESULTS AND CONCLUSIONS: CYP2B6 516TT was associated with greater
      plasma and intracellular exposure to EFV, and greater plasma exposure to NVP.
      Intracellular drug concentration, and CYP2B6 genotype were predictors of EFV
      neuropsychological toxicity. CYP2B6 genotyping may be useful to complement an
      individualization strategy based on plasma drug determinations to increase the
      safety and tolerability of EFV.

PMID- 15864120
TI  - Single nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of
      hypertension.
AB  - CYP2J2 and CYP2C8 metabolize arachidonic acid (AA) to cis-epoxyeicosatrienoic
      acids (EETs), which play a central role in regulating renal tubular fluid
      electrolyte transport and vascular tone. We hypothesized that functionally
      relevant polymorphisms in the CYP2J2 or CYP2C8 genes influence hypertension risk.
      We examined associations between CYP2J2*7 (G-50 T promoter) and CYP2C8*3
      (Arg139Lys and Lys399Arg, which are in 100% linkage disequilibrium) polymorphisms
      and hypertension in a biethnic population from Tennessee. CYP2J2*7 variant allele
      frequency was significantly higher in African-Americans versus Caucasians (14.1%
      versus 7.7%, P=0.01), irrespective of hypertension status. When analysed
      separately by race, the genotype distribution of the CYP2J2*7 variant allele was
      not significantly different among African-Americans with/without hypertension,
      but was significantly different among Caucasians with/without hypertension
      (P=0.03). Indeed, the odds ratio of having hypertension attributable to carrying
      the CYP2J2*7 variant allele adjusted for age, gender, body mass index and family
      history was 0.39 (95% confidence interval 0.17-0.89) among Caucasians, suggesting
      a protective effect. Additional subgroup analyses revealed a significantly lower
      CYP2J2*7 variant allele frequency in hypertensive versus normotensive Caucasian
      males (5.6% versus 12.5%, P=0.02) and in hypertensive versus normotensive
      Caucasians without a family history of hypertension (1.5% versus 11.0%, P=0.03).
      With respect to the CYP2C8*3 variant, genotype distribution and allele
      frequencies were similar between normotensive and hypertensive subjects. This
      study provides evidence for an association between CYP2J2*7 genotype and
      hypertension in Caucasian males and Caucasians without a family history of
      hypertension, but suggests no association between CYP2C8*3 genotype and
      hypertension. Confirmation of these findings in additional populations is
      warranted.

PMID- 15864121
TI  - Variation in the toll-like receptor 4 gene and susceptibility to myocardial
      infarction.
AB  - Variation in the gene encoding toll-like receptor 4 (TLR4), a transmembrane
      receptor that mediates inflammatory responses to bacterial endotoxin, has been
      associated with susceptibility to atherosclerosis and its complications, such as
      myocardial infarction (MI), the pathogenesis of which involves inflammation. A
      recent study has also indicated that TLR4 gene variation influences the effect of
      statin treatment on reducing atherosclerosis complications. We studied the TLR4
      gene Asp299Gly polymorphism in relation to susceptibility to myocardial
      infarction in a cohort of patients with angiographically documented coronary
      artery disease, and performed a meta-analysis using data sets from three
      independent studies. The meta-analysis showed that overall, odds ratio (OR) for
      MI was 0.73 [95% confidence interval (CI) 0.55-0.96, P=0.024] in 299Gly carriers
      compared to non-carriers, and there was no evidence of heterogeneity among the
      sample sets (P=0.679). In our patient cohort, a significant association of 299Gly
      bearing genotypes with lower susceptibility to myocardial infarction was observed
      only in patients receiving statin treatment, with 299Gly carriers having an OR of
      0.49 (95% CI 0.27-0.78, P=0.015) for MI compared to non-carriers. These results
      are consistent with the notion that variation in the TLR4 gene contributes to
      inter-individual variability in susceptibility to coronary ischaemic events, and
      that TLR4 genotype and statin treatment may have a synergistic effect.

PMID- 15864122
TI  - Alpha2B adrenergic receptor 301-303 deletion polymorphism and vascular alpha2
      adrenergic receptor response.
AB  - Postsynaptic alpha2B adrenergic receptors (ARs) mediate vasoconstriction. There
      is more than 1000-fold variability in vascular sensitivity to an alpha2-AR
      agonist. Genetic variability may contribute to such interindividual differences
      in sensitivity. A 301-303 deletion (del) polymorphism has been identified in the
      coding region of the alpha2B-AR gene and has functional effects in vitro. Thus,
      we examined the hypothesis that the del301-303 polymorphism contributes to
      variability in vascular alpha2-AR responses in vivo. Healthy subjects were
      recruited based on their alpha2B-AR genotype. Their vascular sensitivity was
      determined using a linear variable differential transformer following the
      infusion of increasing doses (range 0.01-1000 ng/min) of the alpha2-AR agonist,
      dexmedetomidine, into a dorsal hand vein. The dose that produced 50% (ED50) of
      maximum venoconstriction (Emax) was determined for each subject. Vascular
      response was compared among the three genotypes. Forty-nine subjects were studied
      [28 wild-type wt/wt, 13 wt/del, 8 del/del]. There was no difference in
      dexmedetomidine ED50 and Emax among the alpha2B-AR del301-303 genotypes. The ED50
      was 1.39 ng/min [95% confidence interval (CI) 0.03-63.0 ng/min] in wt/wt
      subjects, 1.63 ng/min (95% CI 0.01-177.8 ng/min) in wt/del and 2.37 ng/min (95%
      CI 0.17-33.7 ng/min) in del/del (P=0.80). The average Emax was 75.4+/-14.9% in
      wt/wt, 75.7+/-21.3% in wt/del and 82.2+/-12.9% in del/del subjects (P=0.26).
      These findings suggest that the del301-303 polymorphism does not contribute
      significantly to interindividual in vivo variability in response to alpha2-AR
      activation in the hand vein.

PMID- 15864123
TI  - Calcium-sensing receptor gene polymorphism Arg990Gly and its possible effect on
      response to cinacalcet HCl.
AB  - Cinacalcet, a novel calcimimetic compound, is effective in reducing parathyroid
      hormone (PTH) levels in approximately 70% of patients with secondary
      hyperparathyroidism. However, interindividual variations in the dose required to
      achieve the treatment goal have been noted in clinical studies. Our investigation
      examined the genetic polymorphisms of the calcium-sensing receptor (CaSR) gene as
      one possible cause of the different responses to cinacalcet. We report data on
      seven end-stage renal failure patients who were treated with regular
      haemodialysis and who participated in clinical trials of cinacalcet. All patients
      had secondary hyperparathyroidism with baseline intact PTH (iPTH) levels greater
      than 600 pg/ml. Three patients were male and four female with a mean+/-SD age of
      60+/-12 years. DNA was extracted from peripheral lymphocytes. An area in exon 7
      of the CaSR gene was amplified by the polymerase chain reaction and sequenced.
      Mean+/-SD baseline iPTH was 1086+/-189 pg/ml. The five patients without Arg990Gly
      demonstrated a 29.7+/-4.0% (+/-SEM) reduction in iPTH from individual baseline.
      One patient was found to be homozygous for the Arg990Gly polymorphism and another
      was heterozygous for both arginine and glycine alleles. The homozygous patient
      showed a significantly higher sensitivity to cinacalcet compared to the other
      patients (P=0.003) with a 76.3+/-7.7% reduction in iPTH from baseline. No
      polymorphisms were noted in codons 986 or 1011. This preliminary study points to
      the possibility that patients homozygous for glycine at the 990 position in exon
      7 of the CaSR may be more sensitive to the calcimimetic drug cinacalcet compared
      to those who are homozygous for arginine at that location.

PMID- 15864124
TI  - Genetic polymorphism in the phenobarbital-responsive enhancer module of the UDP
      glucuronosyltransferase 1A1 gene and irinotecan toxicity.
AB  - Genetic polymorphism of the UDP-glucuronosyltransferase (UGT) 1A1 gene is
      associated with the decreased glucuronidation activity of an active metabolite of
      irinotecan, SN-38, and UGT1A1*28 has been shown as a predictive factor for
      irinotecan toxicity. The phenobarbital-responsive enhancer module (PBREM) of the
      UGT1A1 promoter region has been reportedly associated with the transcriptional
      activity of the gene. We investigated whether the polymorphism of PBREM (T-3279G)
      would affect inter-patient variations in sensitivity to irinotecan toxicity. The
      study population comprised 119 cancer patients who had received irinotecan. We
      reviewed their clinical records, including patient characteristics, and observed
      their toxicity levels following irinotecan infusion. Genotyping was performed by
      sequencing analyses. Logistic regression analyses were performed to assess the
      relationship between genotypes and irinotecan toxicity. We identified the
      homozygotes of the reference allele for T-3279G in 68 patients, the heterozygotes
      in 37, and the homozygotes for the variant in 14. Logistic regression analysis
      indicated a significant association between the homozygotes for T-3279G and the
      severe toxicity (odds ratio 5.80; 95% confidence interval 1.67-20.1). However,
      multivariate analysis, including the data of UGT1A1*28 polymorphism, revealed a
      diminution of the association due to a highly significant linkage disequilibrium
      between these polymorphisms. Our results suggest that a highly significant
      linkage disequilibrium exists between T-3279G and UGT1A1*28 polymorphisms, and
      that the variants of T-3279G and UGT1A1*28 cooperatively decrease transcriptional
      activity of the UGT1A1 promoter. The determination of T-3279G and UGT1A1*28
      genotypes might be clinically useful in predicting severe irinotecan toxicity in
      cancer patients.

PMID- 15864125
TI  - Genetic factors related to unconjugated hyperbilirubinemia amongst adults.
AB  - Some variations in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene are involved
      in the development of unconjugated hyperbilirubinemia. We hypothesize that other
      genetic factors may also be associated with this disease. A total of 227 adults
      with normal routine haematology and liver function (apart from bilirubin testing
      for which they revealed bilirubin > or = 25.7 micromol/l and unconjugated
      bilirubin/total bilirubin > or = 80%), and 235 sex- and age-matched controls,
      were recruited. All subjects were analysed for UGT1A1, glucose-6-phosphate
      dehydrogenase (G6PD) and organic anion transporter polypeptide 2 (OATP2)
      genotypes using polymerase chain reaction-restriction fragment length
      polymorphism. The results indicated that G6PD deficiency, variant UGT1A1 gene and
      variant OATP2 gene were risk factors for hyperbilirubinemia. The odds ratios (OR)
      (with 95% confidence interval) were 220.83 (34.68-1406.30), 73.61 (17.01-318.63),
      45.15 (11.19-182.22), 15.46 (4.35-54.99) and 6.51 (1.83-23.09), respectively, for
      individuals featuring the common UGT1A1/OATP2 haplotypes homozygous/heterozygous,
      compound heterozygous/heterozygous, compound heterozygous/wild-type,
      heterozygous/heterozygous and heterozygous/wild-type variations amongst subjects
      with normal G6PD activity. Amongst the subjects with G6PD deficiency, the OR was
      159.00 (24.57-1028.94) for individuals carrying variations in both UGT1A1 and
      OATP2 genes. The UGT1A1/OATP2 haplotypes homozygous/wild-type,
      homozygous/compound heterozygous and homozygous/homozygous for G6PD normal and
      variant/wild-type for G6PD deficient individuals were only observed in the case
      group, and not in the control group. Amongst hyperbilirubinemic adults, bilirubin
      values tended to parallel variation status of their haplotypes. Adults featuring
      certain haplotypes in UGT1A1, OATP2 and G6PD genes face a high risk of developing
      unconjugated hyperbilirubinemia.

PMID- 15864126
TI  - Genetic and other sources of variation in the activity of serum
      paraoxonase/diazoxonase in humans: consequences for risk from exposure to
      diazinon.
AB  - Diazinon is the only organophosphorus insecticide that is currently approved for
      use in sheep dip in the UK. Reports that some individuals may be genetically more
      susceptible to possible chronic adverse health effects, due to variations in PON1
      activity, are complicated by the reliability of activity measurements. In the
      present study, the influence of three polymorphisms of PON1 on serum diazoxonase
      activity was investigated in 85 healthy volunteers. Serum activity was assessed
      in as close to physiological conditions as possible (at pH 7.4, 150 mM NaCl and
      37 degrees C with 50 microM diazoxon as substrate) and by quantifying pyrimidinol
      formation using high-performance liquid chromatography. PON1 genotypes were
      determined by the polymerase chain reaction and restriction enzyme digestion. For
      PON1 Q192R, individuals with the RR genotype had the highest serum diazoxonase
      activity, in contrast to some previous reports where activity was determined
      under less physiological conditions. Activity was slightly reduced in individuals
      with the QR genotype and activity was reduced even further in those with the QQ
      genotype. For PON1 L55 M, there was a significant decrease in mean enzyme
      activity from LL>LM>MM genotypes. The promoter polymorphism PON1 -108 C/T had
      only a slight effect on activity. Overall, intragenotype variation in PON1
      activity was appreciably greater than the mean intergenotype differences. In
      conclusion, although there is a wide variation in activity in individuals both
      within and between genotypes, those individuals with a combination of Q and M
      alleles generally have a lower ability to detoxify diazoxon, which implies a
      potentially greater susceptibility to toxicity from diazinon.

PMID- 15864127
TI  - Beta2-adrenoceptor gene polymorphisms.
AB  - Beta2-adrenoceptors (AR) play an important role in regulation of vascular and
      bronchial smooth muscle tone; functional beta2-AR, however, also exist in human
      heart where they can mediate positive inotropic and chronotropic effects. Recent
      studies have discovered that beta2-AR are polymorphic. The most common single
      nucleotide polymorphisms (SNPs) are: Arg16Gly, Gln27Glu, Thr164Ile in the coding
      region, and Arg-19Cys in the 5' upstream peptide. These SNPs affect receptor
      function in vitro; however, conflicting data exist on their functional relevance
      in vivo. This might be due to the fact that the four SNPs in the 5' upstream
      peptide and in the coding region, respectively, are linked and form certain
      haplotypes. This review gives an overview on the contribution of beta2-AR
      polymorphisms to cardiovascular diseases or altered drug responses. In addition,
      the relevance of SNPs vs. haplotypes for beta2-AR functional responsiveness is
      discussed.

PMID- 15864128
TI  - A mutation in the drug transporter gene ABCC2 associated with impaired
      methotrexate elimination.
AB  - Human multidrug resistance protein 2 (MRP2, encoded by ABCC2) is involved in
      active efflux of anionic drugs such as methotrexate. MRP2 is expressed on the
      luminal side of hepatocytes and renal proximal tubular cells, indicating an
      important role in drug elimination. We postulated that loss-of-function mutations
      in ABCC2, which are involved in the Dubin-Johnson syndrome, may be associated
      with impaired methotrexate elimination and an increased risk of toxicity. We
      studied the biological phenotype and ABCC2 coding sequence in a patient receiving
      a high-dose methotrexate infusion for large B-cell lymphoma and who had an
      unusual pharmacokinetic profile, mainly characterized by a three-fold reduction
      in the methotrexate elimination rate. This resulted in severe methotrexate over
      dosing and reversible nephrotoxicity. An inversion of the urinary coproporphyrin
      isomer I/III ratio (a specific biological marker of the Dubin-Johnson syndrome)
      was observed in this patient. Genetic analysis of ABCC2 identified a heterozygous
      mutation replacing a highly conserved arginine by glycine in the cytoplasmic part
      of the second membrane-spanning domain (position 412 of MRP2), a region
      associated with substrate affinity. This genetic variant was not found in a
      control population. Functional analysis in transiently transfected Chinese
      hamster ovary cells revealed a loss of transport activity of the G412 MRP2 mutant
      protein. An ABCC2 mutation altering MRP2-mediated methotrexate transport and
      resulting in impaired drug elimination and subsequent renal toxicity was
      identified. Candidates for methotrexate therapy should be considered for MRP2
      functional testing.

PMID- 15864129
TI  - A multilocus approach to the antihypertensive pharmacogenetics of
      hydrochlorothiazide.
AB  - OBJECTIVES: To assess the influence of variations in multiple candidate genes on
      inter-individual variation in diastolic blood pressure (DBP) response to
      hydrochlorothiazide. METHODS: A community-based sample of 585 adults with
      essential hypertension underwent monotherapy with hydrochlorothiazide for 4
      weeks. In a nested case-control design, 195 individuals in the highest tertile of
      DBP response (responders) and 195 individuals in the lowest tertile of DBP
      response (non-responders) were genotyped for 45 polymorphisms in 19 candidate
      genes. For those polymorphisms where the set association approach found to be
      significantly associated with DBP response, logistic regression was performed to
      estimate the odds ratio (OR) for response associated variation in the identified
      genotype/haplotype. RESULTS: Two polymorphisms in the sodium channel gamma
      subunit promotor gene, and a polymorphism in the endothelial nitric oxide
      synthase gene, were significantly associated with blood pressure response to
      hydrochlorothiazide. In the final experiment for the set association model
      P=0.038. In the logistic regression analyses, compared to subjects with the CT/CT
      haplotype of the SCNN1G gene, those with the GA/GA haplotype had OR 5.21 of being
      a DBP responder [95% CI 1.65-16.47]. Compared to subjects with the GT genotype of
      the ENOSA_rs1799983 polymorphism, those with the GG genotype had an OR 2.19 of
      being a DBP responder [95% CI 1.27-3.77]. CONCLUSIONS: Two polymorphisms in the
      sodium channel gamma-subunit promotor gene, and a polymorphism in the endothelial
      nitric oxide synthase gene, were associated with significant differences in odds
      of DBP response to hydrochlorothiazide. Follow-up studies are needed to define
      the functional genetic variations and their mechanisms of pharmacogenetic
      effects.

PMID- 15864130
TI  - Haplotypes of variants in the UDP-glucuronosyltransferase1A9 and 1A1 genes.
AB  - OBJECTIVES: Nine different functional UGT1A enzymes are generated from a single
      UGT1A gene by alternative splicing, with each enzyme having a unique exon 1. SN
      38, the active metabolite of the anticancer agent irinotecan, is metabolized by
      both UGT1A1 and UGT1A9. We aim to characterize the UGT1A9-UGT1A1 haplotypes in
      Asians and Caucasians and gain insights on their functional consequences.
      METHODS: Asian and Caucasian individuals were genotyped for UGT1A1 and UGT1A9
      variants. RESULTS: A higher frequency of the UGT1A9 -118T10 allele was observed
      in Asians compared to Caucasians, while the -275T>A and -2152C>T variants were
      relatively uncommon in Caucasians and not found in Asians. The strongest linkage
      disequilibrium (LD) was observed between the UGT1A1 -53 and -3156 and between the
      UGT1A9 -275 and -2152 loci. Lower LD was observed between the -118 UGT1A9 variant
      and the UGT1A1 variants. Fourteen UGT1A9-UGT1A1 haplotypes were found in Asians,
      seven of them found to be shared by both populations. Common UGT1A9-UGT1A1
      diplotypes were defined, and a difference was observed across the SN-38
      glucuronidation rates in Caucasian livers stratified by diplotypes. CONCLUSION:
      This study for the first time described common UGT1A9-UGT1A1 haplotypes,
      highlighting important ethnic differences between Asians and Caucasians. If the
      functional effect of these haplotypes can be confirmed, this haplotypic
      information would be applicable to the correct design of prospective clinical
      studies of irinotecan, as well as of other drugs primarily metabolized by both
      UGT1A1 and UGT1A9.

PMID- 15864131
TI  - Acute effects of pravastatin on cholesterol synthesis are associated with SLCO1B1
      (encoding OATP1B1) haplotype *17.
AB  - OBJECTIVE: The aim was to investigate whether polymorphisms in the SLCO1B1 gene,
      encoding the hepatic uptake transporter OATP1B1, influence the short-term effects
      of pravastatin on cholesterol synthesis. METHODS: We determined plasma
      concentrations of lathosterol and cholesterol up to 12 h after intake of a single
      dose of 40 mg pravastatin in 41 healthy Caucasian subjects, in whom SLCO1B1
      single nucleotide polymorphisms (SNP; 521T>C and -11187G>A) and haplotypes (*15B
      and *17) had been previously shown to be associated with considerably elevated
      plasma pravastatin levels. RESULTS: The effects of pravastatin on plasma
      lathosterol concentration and lathosterol to cholesterol concentration ratio,
      which are established markers of the rate of cholesterol synthesis in vivo, were
      significantly smaller among the three heterozygous carriers of the SLCO1B1 *17
      haplotype (containing the -11187G>A, 388A>G and 521T>C SNPs) as compared with non
      carriers. Significant inverse relationships were found between pravastatin area
      under the concentration-time curve (AUC) values and effects of pravastatin on
      lathosterol and lathosterol to cholesterol ratio among the whole study
      population. CONCLUSION: These results suggest that uptake of pravastatin into
      hepatocytes is impaired in carriers of the SLCO1B1 haplotype *17, resulting in
      higher plasma pravastatin concentrations but lower concentrations of pravastatin
      in hepatocytes and thereby in a smaller inhibitory effect on cholesterol
      synthesis. The cholesterol-lowering response to pravastatin may be impaired in
      carriers of the *17 haplotype.

PMID- 15864132
TI  - The manganese superoxide dismutase Ala16Val dimorphism modulates both
      mitochondrial import and mRNA stability.
AB  - A genetic dimorphism incorporates either alanine (Ala) or valine (Val) in the
      mitochondrial targeting sequence (MTS) of manganese superoxide dismutase (MnSOD).
      The Ala-MTS confers a 40% higher MnSOD activity than the Val-MTS after import
      into isolated mitochondria in vitro. The present study aimed to characterize
      functional consequences in whole cells. HuH7 human hepatoma cells were
      transfected with vectors encoding for the human Ala- or Val-MnSOD variants fused
      to a Myc-His-tag. The Ala-variant resulted in four-fold higher levels of the
      mature exogenous protein and MnSOD activity than the Val-variant. Studies with a
      proteasome inhibitor indicated that precursor proteins are either imported into
      the mitochondria or degraded by the proteasome. Despite identical levels 8 h
      after transfection, mRNA levels at 36 h were two-fold higher for the Ala-encoding
      mRNA than the Val-mRNA. Decreasing the mitochondrial membrane potential decreased
      both MnSOD mitochondrial import and its mRNA levels. Much larger differences in
      the activity of the human Val- and Ala-MnSOD variants are observed in whole cells
      rather than after import experiments performed in vitro. First, the slowly
      imported Val-MnSOD is degraded by the proteasome in cells. Second, the slower
      mitochondrial import of the Val-variant may be associated with decreased mRNA
      stability, possibly due to impaired cotranslational import.

PMID- 15864133
TI  - Human adenosine 2B receptor: SNP discovery and evaluation of expression in
      patients with cystic fibrosis.
AB  - OBJECTIVES AND METHODS: We analyzed the adenosine 2B (A2B) receptor gene, which
      consists of two exons, for single nucleotide polymorphisms (SNPs) and tested the
      hypothesis that coding sequence polymorphisms in the gene contribute to disease
      state in patients with cystic fibrosis (CF). Using PCR and restriction fragment
      length polymorphism (RFLP) analysis, we assessed 53 American subjects of mixed
      ethnicity, 64 European Caucasian control subjects and 148 Caucasian patients with
      CF for A2B SNPs. RESULTS: We identified one SNP in the 5' untranslated region
      (UTR) and seven SNPs in the open reading frame. One SNP was identified in the
      coding region of a German patient with CF but in none of the American subjects.
      No other SNPs were found in CF patients. A nonsynonymous SNP was identified in
      exon 2 of the German controls with an allelic frequency of 11%. The US subjects
      were of mixed ethnicity and most frequently (10.4%) had a SNP in the 5'UTR; 7
      coding SNPs occurred in <3%. All SNPs other than the Leu96Phe and Gly136Arg
      variants were found only in African-Americans. Of the 26 African-Americans who
      were genotyped, 42% were hypertensive but the study group was too small to show
      an association between blood pressure status and SNP expression. CONCLUSIONS: The
      data show that SNPs in the A2B receptor gene are much more frequent in African
      Americans than in Caucasians and that German Caucasians, but not African
      Americans, express Gly136Arg. None of the SNPs identified in A2B receptors are
      likely to be modifiers in CF.

PMID- 15864134
TI  - Increase in the transcriptional activity of the endothelial nitric oxide synthase
      gene with fluvastatin: a relation with the -786T>C polymorphism.
AB  - HMG-CoA reductase inhibitors (statins) increase endothelial nitric oxide (NO)
      production, although the precise mechanism of this statin induced increase in NO
      production remains to be elucidated. We examined endothelial nitric oxide
      synthase (eNOS) mRNA levels, mRNA stability and the transcriptional activities of
      the eNOS gene in human umbilical vein endothelial cells treated with fluvastatin
      and simvastatin. We further examined whether the effects of these statins differ
      dependent upon the -786T>C polymorphism in the eNOS gene, and whether these
      statins affect gene expression of replication protein A1 (RPA1), which is known
      to reduce the transcriptional activity of the eNOS gene with the -786C allele.
      Utilizing the real-time reverse transcription-polymerase chain reaction,
      fluvastatin significantly increased eNOS mRNA levels and mRNA stability, and
      decreased RPA1 mRNA levels. Luciferase reporter gene assays revealed that
      fluvastatin significantly increased the transcriptional activity of the eNOS
      gene. The effect of fluvastatin was stronger in the -786C/C genotype than in the 
      786T/T genotype. Simvastatin increased eNOS mRNA levels and mRNA stability, but
      did not affect the transcriptional activity of the eNOS gene. Fluvastatin
      increased eNOS mRNA levels by enhancing both the transcriptional activity and
      mRNA stability. The effect of fluvastatin on the transcriptional activity was
      augmented in the -786C/C genotype, probably because of a decrease in RPA1 gene
      expression. Simvastatin increased eNOS mRNA levels only by enhancing mRNA
      stability. The present study suggests that fluvastatin increases endothelial NO
      activity and thus may be more beneficial to patients with the -786C allele.

PMID- 15864135
TI  - Functional characterization of a novel polymorphism of pregnane X receptor,
      Q158K, in Chinese subjects.
AB  - The pregnane X receptor (PXR) is the main transcriptional regulator of many
      enzymes that metabolize xenobiotics such as P450s and drug transporters.
      Polymorphisms in the PXR gene contribute to population variability in CYP3A4 and
      P-glycoprotein levels. Single nucleotide polymorphisms (SNPs) have been reported
      in Caucasian, African-American and Japanese populations. In the present study, we
      identified the known SNP, V140M and a novel SNP, Q158K, in Chinese subjects. We
      developed an allele-specific polymerase chain reaction method to detect the novel
      allele and found its frequency in 451 Chinese subjects to be 2.2%. CYP3A4
      luciferase reporter assays revealed that the Q158K variant gave rise to much
      lower levels of CYP3A4 promoter activity in LS174T and HepG2 cells exposed to the
      PXR ligands, rifampin and paclitaxel, than did wild-type PXR. The SNP had less
      effect on promoter activity in response to clotrimazole or nifedipine.

PMID- 15864136
TI  - Microsatellite polymorphisms in the epidermal growth factor receptor (EGFR) gene
      and the transforming growth factor-alpha (TGFA) gene and risk of oral cancer in
      Puerto Rico.
AB  - OBJECTIVES AND METHODS: Risks of oral cancer related to a CA microsatellite
      repeat polymorphism in intron 1 of the epidermal growth factor receptor (EGFR)
      gene and a TaqI polymorphism in the transforming growth factor-alpha (TGFA) gene
      were evaluated in a population-based case-control study consisting of 157 cases
      and 149 controls recruited in Puerto Rico. RESULTS: Carriers of > or = 16 CA
      repeats in EGFR showed a 1.9-fold increased risk for oral cancer (OR=1.9, 95%
      CI=1.0-3.5). Risks also tended to increase with decreasing number of alleles with
      > or = 16 CA repeats (P for trend=0.06). Our data suggested a non-significant
      reduction in risk for subjects heterozygous for the TGFA polymorphism (OR=0.6,
      95% CI=0.2-1.3). CONCLUSIONS: The EGFR-associated risk appeared to be independent
      of tobacco and alcohol use and may be restricted primarily to subjects who
      consumed low amounts of fresh fruits and vegetables (OR=5.9, 95%CI: 2.3-15.2).
      These data implicate dietary and molecular targets for oral cancer prevention.

PMID- 15864137
TI  - Vitamin D receptor gene polymorphisms, particularly the novel A-1012G promoter
      polymorphism, are associated with vitamin D3 responsiveness and non-familial
      susceptibility in psoriasis.
AB  - Psoriasis is a genetically determined disease characterized by hyperproliferation
      and disordered maturation of the epidermis. Th1 lymphocytes are implicated in its
      pathogenesis. The vitamin D receptor (VDR) is a candidate modifying gene, having
      immunosuppressive effects and being involved in anti-proliferative and pro
      differentiation pathways in keratinocytes. There is suggestive evidence that the
      A allele of the A-1012G polymorphism is associated with down-regulation of the
      Th1 response, via GATA-3. The F and T alleles of Fok1 and Taq1 have been
      associated with increased VDR activity. The present study aimed to test the
      hypothesis that the A allele of A-1012G is protective for occurrence and severity
      of psoriasis and enhances therapeutic response to vitamin D analogues and that
      these effects would be additive to those of Fok1 and Taq1. The study group
      comprised 206 psoriasis patients who had received topical calcipotriol treatment
      and 80 controls. There was no significant linkage disequilibrium between any pair
      of the three polymorphic sites (P=0.3-0.8). The A, F and T alleles were
      positively associated with calcipotriol response: AA genotype (compared to
      AG/GG), odds ratio (OR)=2.18 (P=0.04); TT, OR=1.97 (P=0.03); AAFF genotype
      combination, OR=4.11 (P=0.03); AATT, OR=5.64 (P=0.005); and FFTT, OR=3.22
      (P=0.01). Comparing patients without, to patients with, a family history of
      psoriasis, the A allele was under represented (P=0.01) and the AAFF genotype
      combination even more so (compared to residual genotypes) (OR=0.24; P=0.005).
      AAFF was also under-represented in patients without a family history compared to
      controls (OR=0.31; P=0.04). There were no associations of family history with
      Fok1 and Taq1. There were no associations of severity of psoriasis with any
      polymorphism. In conclusion, the A-1012G, Fok1 and Taq1 VDR polymorphisms were
      associated with response to calcipotriol. A-1012G and Fok1 were associated with
      susceptibility to non-familial psoriasis.

PMID- 15864138
TI  - Alpha-2B adrenoceptor polymorphism and peripheral vasoconstriction.
AB  - OBJECTIVES: Alpha-2B adrenoceptors (AR) mediate vasoconstriction in the mice. A
      human alpha-2B AR deletion (D) variant has been associated with loss of short
      term agonist-promoted receptor desensitization, which may lead to increased
      vasoconstriction upon alpha-2 AR activation. This study tested the hypothesis
      that alpha-2 AR activation will induce enhanced vasoconstriction in carriers of
      the alpha-2B AR DD genotype, compared to carriers of the II or the DI genotypes.
      METHODS: We administered 1 microg/kg dexmedetomidine (an alpha-2 agonist)
      intravenously to 80 surgical patients in whom sympatholytic effects of the drug
      were attenuated by general anesthesia. Measurements were made of finger blood
      volume (an indicator of vasoconstriction) by photoplethysmographic determination
      of light transmission through a finger (LTF) and of hemodynamic variables.
      RESULTS: Dexmedetomidine increased LTF (vasoconstriction), induced an initial
      increase in systolic blood pressure and decreased heart rate in all genotype
      groups (P<0.0001 for all). Three min after the start of dexmedetomidine infusion,
      the increase in LTF was more pronounced (P=0.014) in the DD group compared to the
      DI and II groups. There were no significant differences in LTF values between the
      groups at the end of or 5 min after dexmedetomidine infusion. There were no
      differences in systolic blood pressure or heart rate values between the groups
      during or after the dexmedetomidine infusion. CONCLUSIONS: The results of this
      study confirm that the alpha-2 agonist dexmedetomidine induced marked peripheral
      vasoconstriction. Subjects with the alpha 2B DD genotype had an enhanced
      vasoconstrictive response at the beginning of dexmedetomidine infusion. However,
      this enhanced vasoconstrictive response was not sustained throughout or after the
      15-min dexmedetomidine infusion.

PMID- 15864139
TI  - Pharmacogenetic testing for drug metabolizing enzymes: is it happening in
      practice?
AB  - It is widely claimed that pharmacogenetics may form the basis of 'personalized
      medicine'. We sought to determine the current utilization of pharmacogenetic
      testing for drug metabolizing enzymes (DMEs). The hypothesis was that these tests
      were rarely performed clinically. Questionnaires were sent to 629 individuals
      representing laboratories, hospitals and universities throughout Australia and
      New Zealand. The questionnaires asked which facilities performed pharmacogenetic
      tests for selected DMEs, and details about the tests, if performed. The overall
      response rate was 81.1% (510/629); three respondents declined to participate.
      Clinical genotyping and phenotyping tests for DMEs could be performed by 10 (2.0%
      of 507) and 18 (3.6%) facilities, respectively. The most frequently performed
      genetic tests were for thiopurine methyltransferase (approximately 400 times in
      2003) and pseudocholinesterase (approximately 250 times). The frequency of
      phenotyping exceeded genotyping by five- and eight-fold, respectively. One centre
      performed CYP2D6 phenotyping frequently (approximately 4200 times in 2003) for
      perhexiline. Genotyping and phenotyping tests for other cytochrome P450 enzymes,
      N-acetyltransferase-2 and dihydropyrimidine dehydrogenase were effectively never
      undertaken for clinical purposes. Pharmacogenetic tests for DMEs are currently
      performed rarely in clinical practice, despite repeated claims that they may
      benefit patient care. The only tests performed with any regularity in Australasia
      are for thiopurine methyltransferase and pseudocholinesterase, and CYP2D6
      phenotyping in one centre for patients on perhexiline. The low clinical
      utilization reflects a poor evidence base, unestablished clinical relevance and,
      in the few cases with the strongest rationale, a slow translation to the clinical
      setting.

PMID- 15864140
TI  - Range of motion in reconstruction situations following corpectomy in the lumbar
      spine: a question of bone mineral density?
AB  - STUDY DESIGN: In vitro biomechanical study to evaluate the stability of different
      types of instrumentation in the lumbar spine following corpectomy in relation to
      bone mineral density (BMD). OBJECTIVES: To investigate the relation between the
      stability of a spinal instrumentation and BMD. To determine a threshold value of
      BMD allowing a single ventral instrumentation following corpectomy in the lumbar
      spine. SUMMARY OF BACKGROUND DATA: Some in vitro studies determined the
      biomechanical properties of different spinal instrumentations in various spinal
      injury models. To the authors' knowledge, there are no published data available
      concerning stabilization in relation to BMD. A guideline for the treatment of a
      corpectomy depending on BMD would be helpful in order to choose the appropriate
      surgical method. METHODS: Twenty-four fresh frozen human lumbar cadaveric spine
      specimens L1-L3 were used for testing of biomechanical properties. Plain
      radiographs were taken. BMD was determined using quantitative computed tomography
      (QCT). Testing in a 6 df loading device included native specimens and specimens
      after corpectomy of L2, restoration of the defect with a titanium cage, and two
      reconstruction situations: single ventral and additional dorsal instrumentation.
      Load-displacement curves and range of motion parameters were recorded and
      correlated with BMD. RESULTS: A significant (P < 0.05) influence of BMD on range
      of motion was found. Single ventral instrumentation was critical concerning axial
      rotation. Combined dorsoventral instrumentation offered sufficient stability. The
      threshold value for use of single ventral instrumentation is a BMD > or = 0.22
      g/cm. CONCLUSIONS: Single ventral instrumentation can provide sufficient
      stability following corpectomy in the lumbar spine under the condition of a high
      BMD. Determination of BMD and the use of this guideline provides a valid tool for
      surgical planning.

PMID- 15864141
TI  - A safe screw trajectory for atlantoaxial transarticular fixation achieved using
      an aiming device.
AB  - STUDY DESIGN: A retrospective evaluation and characterization of the trajectory
      of atlantoaxial transarticular screws inserted using an aiming device.
      OBJECTIVES: To confirm that the screws were inserted through the safest
      trajectory, which is through the most dorsal and medial part of the isthmus of
      C2, and to characterize the trajectory on lateral radiograms by comparison with
      historical controls. SUMMARY OF BACKGROUND DATA: Posterior atlantoaxial
      transarticular screw fixation entails the potential risk of vertebral artery (VA)
      injury, which may be lethal. Although much literature recommends that the screws
      should be inserted aiming at the anterior arch of C1, the authors considered that
      the safest screw path is via the most dorsal and medial part of the isthmus
      regardless of the C1 anterior arch, and have used an original aiming device to
      achieve this trajectory. METHODS: Forty-three consecutive patients who submitted
      to atlantoaxial transarticular screw fixation using the aiming device were
      evaluated for screw position using computed tomography (CT) and lateral
      radiogram. The medialization index (the distance between the screw and the cortex
      of the spinal canal of C2 on axial CT) and the dorsalization index (the thickness
      of the bone remaining dorsal to the screw at the isthmus of C2 on sagittal
      reconstruction CT) were measured. Further, three parameters on the lateral
      radiograms of these patients were compared with those in the literature and those
      of our previous cases performed without the aiming device. RESULTS: Neither VA
      injury nor violation of the spinal canal was encountered, although 12 high-riding
      VAs were included in this series. The mean medialization index was 0.21 mm, and
      the indexes of 86.3% of the screws were zero. The mean dorsalization index was
      0.36 mm, and the indexes of 76.8% of the screws were zero. These results
      demonstrated that most of the screws were inserted as aimed, proving the
      usefulness of the aiming device. The trajectory of these screws on lateral
      radiograms was characterized by significantly less bone thickness dorsal to the
      screw at the isthmus compared with the two control groups. As a result, more
      screws were pointed above the anterior arch of C1. CONCLUSIONS: The atlantoaxial
      transarticular screw was inserted safely as aimed by using the aiming device. The
      trajectory was characterized by less bone thickness dorsal to the screw on
      lateral radiogram, which should be a new intraoperative landmark for screw
      insertion, in place of the anterior arch of C1.

PMID- 15864142
TI  - Platelet gel (AGF) fails to increase fusion rates in instrumented posterolateral
      fusions.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine the effect on
      fusion of adding platelet gel to autologous iliac crest graft. SUMMARY OF
      BACKGROUND DATA: Platelet gel is an osteoinductive material prepared by ultra
      concentration of platelets and contains multiple growth factors. Proprietary
      commercial methods are available for harvesting autologous platelet gel
      concentrates for use as graft supplement in spine fusions. METHODS: We reviewed
      76 consecutive patients who underwent instrumented posterolateral lumbar fusion
      with autologous iliac crest bone graft mixed with autologous growth factor (AGF).
      A control group was randomly selected from patients who underwent instrumented
      posterolateral lumbar fusion with autologous bone graft alone. The groups were
      matched for age, sex, smoking history, and number of levels fused. Demographic,
      surgical, and clinical data were collected from medical records. Diagnosis of
      nonunion was based on exploration during revision surgery or evidence of nonunion
      on computerized tomography. The Fisher exact test was used to compare fusion
      rates. RESULTS: In both groups, mean age was 50 years, and 24% were smokers. The
      nonunion rate was 25% in the AGF group and 17% in the control group. This
      difference was not statistically significant (P = 0.18). CONCLUSIONS: Platelet
      gel preparation requires blood draws from the patient. This procedure adds to the
      risk and cost of surgery. The technique for AGF harvest evaluated in this study
      provides the highest concentration of platelets among the commercially available
      methods. Despite this, we showed that platelet gel failed to enhance fusion rate
      when added to autograft in patients undergoing instrumented posterolateral spinal
      fusion. The authors do not recommend the use of platelet gel to supplement
      autologous bone graft during instrumented posterolateral spinal fusion.

PMID- 15864144
TI  - Ossification of the posterior atlantoaxial membrane and the transverse atlantal
      ligament.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report a case of ossification of the
      posterior atlantoaxial membrane (PAAM) and ossification of the transverse
      ligament of the atlas (TAL). SUMMARY OF BACKGROUND DATA: Ossification of the PAAM
      and TAL are both very rare clinical entities. This is the first case involving
      ossification of both the PAAM and TAL with the development of cervical
      myelopathy. METHODS: Patient's history, physical examination, radiographic
      evaluation, surgical treatment, and outcome are examined. Relevant literature is
      also reviewed. RESULTS: The patient's neurological symptoms significantly
      improved after posterior decompressive surgery. CONCLUSION: Ossification of
      various parts of the spinal ligament have been reported previously. Among them,
      ossification of both the PAAM and TAL has never been reported previously and is
      thus extremely rare. Surgical intervention improved the neurological impairment.

PMID- 15864145
TI  - Intradural extramedullary spinal ependymoma: a benign pathology?
AB  - STUDY DESIGN: Spinal ependymoma is a benign central nervous system tumor
      described as an intramedullary lesion more frequently located at the conus
      medullaris. It has been described exceptionally in the literature as an
      intradural extramedullary tumor. OBJECTIVE: Presentation of an extremelly rare
      location and evolution of extremedullary ependymoma and discussion of its
      probable origin, differential diagnosis, treatment options, and follow-up.
      SUMMARY OF BACKGROUND DATA: This case demonstrates an unusual location of a
      benign ependymal tumor in the extramedullary space with a total resection, which
      recurred in a lower level with a malignant transformation with the same
      extramedullary location. METHODS: The authors present the case of a 47-year-old
      woman with a subacute spinal cord dysfunction and an intradural extramedullary D2
      D3 tumor mimicking meningioma or neurinoma. At surgery, an encapsulated
      intradural extramedullary mass was found, but neither dural attachment nor
      medullary infiltration was present. RESULTS: After complete resection, anatomic
      pathologic studies confirmed that the lesion was a benign classic ependymoma.
      Good neurologic outcome was achieved, and no residual tumor was present at
      magnetic resonance imaging (MRI) control performed at 3 and 9 months later. One
      year after surgery, a new intradural extramedullary tumor was found at the D4
      level without recurrence at D2. The patient was operated on again, but at this
      time the histologic study showed an anaplastic ependymoma with a proliferation
      index of 25% measured by Ki-67. Whole central nervous system radiotherapy was
      performed. CONCLUSION: All of the previously reported cases of spinal intradural
      extramedullary ependymomas carried out a benign course. The case we are reporting
      is the first one in which malignant transformation occurred. This tumor should be
      taken into account in the differential diagnosis of intradural extramedullary
      lesions. Moreover, close follow-up is recommended for this unusual location of
      ependymomas.

PMID- 15864146
TI  - Posterior transcanal lumbar interbody fusion for septic vertebral fracture
      pseudarthrosis and sitting imbalance.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe a new method to treat septic
      pseudarthrosis of the lumbar spine via a transcanal approach. SUMMARY OF
      BACKGROUND DATA: Septic pseudarthrosis of the spine after multiple unsuccessful
      anterior and posterior surgeries for vertebral fracture represents a challenge
      for spine surgeons. METHODS: Septic pseudarthrosis associated with dorsal fistula
      developed in a 40-year-old paraplegic man after unsuccessful combined anterior
      and posterior instrumentation for L3-burst fracture and sagittal sitting
      imbalance caused by collapsing spine. RESULTS: The instrumentation was removed
      together with meticulous pseudarthrosis debridement, fistula excision, and
      intravenous antibiotics plus continuous irrigation. Three months later, the
      pseudarthrosis area was approached via a posterior transcanal route because of
      the preceding multiple anterior transperitoneal and retroperitoneal surgeries.
      Posterior interbody instrumentation and fusion were performed with titanium mesh
      cages filled with autologous iliac bone graft. Pedicle screw-rod instrumentation
      was additionally applied to reinforce the interbody fusion and restore lumbar
      lordosis. Following this operation, the patient was ambulated with a custom made
      plastic jacket in his wheelchair. The postoperative course was uneventful, and
      the patient regained his sitting ability progressively. Four months later, the
      blood count analysis was within normal limits. Radiologically, there was a
      complete fusion at the level of instrumentation, while the preoperative lost
      lumbar lordosis was sufficiently restored. The patient was reemployed 6 months
      after surgery in his previous work in a sitting position, and, during the last
      observation 4 years later, he had normal labor analysis and lumbar lordosis.
      CONCLUSION: This extremely rare case focuses on the use of the transcanal
      approach to treat adequately lumbar septic pseudarthrosis and restore lumbar
      lordosis in definitively paraplegic patients in whom no anterior approach can be
      used.

PMID- 15864148
TI  - Long-term effect of a combined exercise and motivational program on the level of
      disability of patients with chronic low back pain.
AB  - STUDY DESIGN: A prospective clinical randomized controlled trial. OBJECTIVES: To
      determine the long-term effect of a combined exercise and motivational program on
      the level of disability of patients with chronic and recurrent low back pain
      (LBP). SUMMARY OF BACKGROUND DATA: There is agreement on the importance of
      exercise during the course of chronic LBP. However, it is well known that long
      term adherence with exercises is particularly low. METHODS: A total of 93
      patients with LBP were randomly assigned to the control group (standard exercise
      program) or the motivational group (combined exercise and motivational program).
      Follow-up assessments were performed at 3.5 weeks, 4 months, 12 months, and 5
      years. Main outcome measures were disability scores, pain intensity, and working
      ability. In addition to classic statistics, the sophisticated linear partial
      credit model was used to test the effects of treatment on disability scores.
      RESULTS: In both groups, significant improvements in the disability scores were
      found at all points of follow-up assessment, however, the cumulative effect of
      the treatment in the motivational group was more than twice as much as in the
      control group. This result is in accordance with the increasing divergence in
      pain intensity between groups between 12 months and 5 years after intervention. A
      significant, positive long-term effect at the 5-year reassessment in working
      ability was only seen in the motivational group. All statistically significant
      results were confirmed by intention-to-treat analyses. CONCLUSIONS: Regarding
      long-term efficacy, the combined exercise and motivation program was superior to
      the standard exercise program. Five years after the supervised combined exercise
      and motivational program, patients had significant improvements in disability,
      pain intensity, and working ability.

PMID- 15864149
TI  - Comparison of Healos/bone marrow to INFUSE(rhBMP-2/ACS) with a collagen-ceramic
      sponge bulking agent as graft substitutes for lumbar spine fusion.
AB  - STUDY DESIGN: A rabbit lumbar intertransverse process arthrodesis model was used
      to evaluate the efficacy of two different bone substitute materials: 1) collagen
      hydroxyapatite sponge (Healos bone void filler) combined with heparinized bone
      marrow; and 2) recombinant human bone morphogenetic protein-2 delivered in a
      collagen sponge (INFUSE Bone Graft) wrapped around an additional collagen-ceramic
      sponge (Mastergraft Matrix) as a "bulking agent." OBJECTIVES: To compare the
      relative efficacy of two different bone graft substitutes to achieve
      posterolateral lumbar spine fusion in rabbits. SUMMARY OF BACKGROUND DATA:
      Autogenous bone graft is considered the gold standard graft material for spine
      fusion. Complications with its use, however, may occur in as many as 30% of
      patients. A variety of bone substitutes have been used for spine fusion, but
      there are few direct comparison experiments to determine the relative efficacy of
      any two alternatives. METHODS: Adult New Zealand white rabbits (n = 24) were
      divided into two groups and underwent bilateral posterolateral intertransverse
      process spine arthrodesis at L5-L6. The fusions were augmented by different bone
      substitute materials as follows: Group 1 (n = 12) received 3 mL of collagen
      hydroxyapatite sponge (Healos bone void filler) (10 x 30 x 5 mm, two per side)
      with 3.0 mL of heparinized bone marrow on each side of the spine. (ratio 1:1);
      Group 2 (n = 12) received 1.5 mL of rhBMP-2 (0.43 mg/mL solution) on a Type 1
      collagen sponge (INFUSE Bone Graft) wrapped around an additional 1.5 mL collagen
      ceramic (15%HA/85%TCP) sponge (Mastergraft Matrix) as a bulking agent to provide
      3 mL of graft on each side of the spine. Bone marrow was aspirated from posterior
      iliac crest, and 1 mL of bone marrow was sent to count number of nucleated cells.
      The rabbits were killed after 8 weeks; the spines were evaluated by manual
      palpation, radiographs (plain radiograph and CT scan), tensile mechanical
      testing, and nondecalcified histology. RESULTS: The bone marrow had average of
      total nucleated cell count 9 x 10 cells. All rabbits (100%) in Group 2
      (INFUSE/Mastergraft Matrix) achieved solid spinal fusions by manual palpation and
      radiographs, whereas solid spinal fusion was not achieved by manual palpation and
      radiographs in any of the rabbits treated with Healos combined with heparinized
      bone marrow (Group 1). The plain radiograph and CT scans of Group 1 showed some
      minimal new bone formation near the transverse processes, but none of these
      rabbits formed a continuous fusion mass. In contrast, all of plain radiographs
      and CT scans in Group 2 showed continuous fusion mass and complete graft
      incorporation between transverse processes bilaterally. Biomechanically, the
      relative strength and relative stiffness values of L5-L6 (fusion segment) in
      Group 2 were statistically significant greater than L5-L6 in Group 1 (P < 0.001).
      Histologic sections confirmed the palpation and radiographic results. CONCLUSION:
      From the manual palpation, radiographic and biomechanical assessment of fusion,
      the results in this study showed that INFUSE (rhBMP-2/collagen sponge)
      consistently produced spine fusion when wrapped around a collagen-ceramic sponge
      bulking agent (Mastergraft Matrix). Meanwhile, Healos was ineffective as a bone
      graft material when combined with heparinized autogenous bone marrow.

PMID- 15864151
TI  - The histologic effects of pulsed and continuous radiofrequency lesions at 42
      degrees C to rat dorsal root ganglion and sciatic nerve.
AB  - STUDY DESIGN: Experimental histologic study of the effects of radiofrequency (RF)
      or convective heating of the rat dorsal root ganglion or sciatic nerve to 42
      degrees C. OBJECTIVE: To determine whether treatment causes neuropathologic
      changes in an effort to explore the mechanisms and safety of pulsed RF pain
      therapy. SUMMARY OF BACKGROUND DATA: Clinical data suggest that low temperature
      pulsed RF energy delivered to the DRG is a safe and effective form of therapy for
      low back pain. However, the mechanism by which this treatment modifies pain is
      unclear. METHODS: A total of 118 Sprague-Dawley rats were divided into five
      groups for different RF and thermal treatments. All treatments increased tissue
      temperature to 42 degrees C. Treatments of the DRG included pulsed RF, continuous
      RF, and conductive heat. The generator output was increased until 42 degrees C
      was obtained in the tissue and was then maintained for 120 seconds. As a positive
      control, some rat sciatic nerves were treated with continuous RF lesions at 80
      degrees C. Animals were killed for histologic study at 2, 7, or 21 days after
      treatment. Tissue was fixed in gluteraldehyde and embedded in plastic resin for
      detailed light microscopic neuropathologic evaluation. RESULTS: The methods used
      to heat the tissue to 42 degrees C caused no significant difference in pathology.
      However, subclinical changes included endoneurial edema caused by alterations in
      the function of the blood-nerve barrier, fibroblast activation, and collagen
      deposition. Tissue returned to normal conditions by 7 days in nerve and 21 days
      in the DRG. These minor structural changes observed at the light microscopic
      level in normal animals do not exclude the possibility that there would be
      nonstructural changes in gene expression or cytokine upregulation in injured
      tissue. Lesions at 80 degrees C caused consistent thermal injury characterized by
      Wallerian degeneration of nerve fibers. CONCLUSIONS: The data support the
      hypothesis that pulsed RF treatment does not rely on thermal injury of neurologic
      tissue to achieve its effect.

PMID- 15864152
TI  - Effect of noxious electrical stimulation of the peroneal nerve on stretch reflex
      activity of the hamstring muscle in rats: possible implications of neuronal
      mechanisms in the development of tight hamstrings in lumbar disc herniation.
AB  - STUDY DESIGN: The effect of noxious electrical stimulation of the peroneal nerve
      on the stretch reflex electromyogram activity of the hamstring muscle
      (semitendinous) was studied. OBJECTIVE: To verify the following hypothetical
      mechanisms underlying tight hamstrings in lumbar disc herniation: stretch reflex
      muscle activity of hamstrings is increased by painful inputs from an injured
      spinal nerve root and the increased stretch reflex muscle activity is maintained
      by central sensitization. SUMMARY OF BACKGROUND DATA: It is reported that stretch
      reflex activity of the trunk muscles is induced by noxious stimulation of the
      sciatic nerve and maintained by central sensitization. METHODS: In spinalized
      rats (transected spinal cord), the peroneal nerve was stimulated electrically as
      a conditioning stimulus. Stretch reflex electromyogram activity of the
      semitendinous muscle was recorded before and after the conditioning stimulus.
      RESULTS: Even after electrical stimulation was terminated, an increased stretch
      reflex activity of the hamstring muscle was observed. CONCLUSIONS: It is likely
      that a central sensitization mechanism at the spinal cord level was involved in
      the increased reflex activity. Central sensitization may play a part in the
      neuronal mechanisms of tight hamstrings in lumbar disc herniation.

PMID- 15864153
TI  - Fulcrum assisted soft stabilization system: a new concept in the surgical
      treatment of degenerative low back pain.
AB  - STUDY DESIGN: An experimental study on cadaver spine and spine model for
      biomechanical evaluation of a novel dynamic stabilization device. OBJECTIVES:
      First, to test the hypothesis that in dynamic stabilization of a lumbar spine
      using pedicle screws and ligament, addition of a fulcrum in front of the ligament
      can unload the disc. Second, to determine the relationship between the length and
      stiffness of the fulcrum and the ligament on disc unloading, lordosis and motion
      preservation. SUMMARY OF BACKGROUND DATA: Activity related low back pain may be
      attributable to abnormal disc loading or abnormal movement. Spinal fusion
      addresses both the mechanisms, but it has limitations. Soft stabilization with
      Graf ligament restricts abnormal movement but increases the disc pressure. The
      Dynesys system uses a plastic cylinder around the ligament to prevent overloading
      the disc, but it restricts extension and loses lordosis. METHODS: A novel dynamic
      stabilization system (fulcrum assisted soft stabilization or FASS) was developed
      in which a flexible fulcrum was placed in front of a ligament between the pedicle
      screws. It was hypothesized that the fulcrum should transform the compressive
      force of a ligament behind into a distraction force in front and unload the disc.
      Three spine models were developed using wooden blocks for vertebral bodies and
      neoprene rubber of different hardness for disc. Their load-deformation character
      was tested and compared with that of the cadaver spine in a spine tester. The
      spine model with the closest load-deformation property to cadaver spine was then
      tested for the effect of a FASS system, consisting of high density polythene rod
      as fulcrums and rubber "O" rings as ligaments. The disc pressure in the spine
      models were recorded with strain gauge in the center. RESULTS: Application of
      ligaments alone across the pedicle screws increased the disc pressure, produced a
      lordosis, and reduced the range of motion. Application of fulcrums reduced the
      disc pressure and maintained the lordosis. Increasing the fulcrum length resulted
      in progressive unloading of the disc but increased stiffness of the motion
      segment. As the fulcrum length approximated the height of the motion segment, the
      lordosis was lost, and the disc was completely unloaded. Decreasing the lateral
      bending stiffness of the fulcrum had minimal effect on disc unloading and motion
      segment stiffness. CONCLUSION: The novel FASS system can unload the disc, control
      the range of motion, and maintain lordosis. These parameters may be controlled
      with a suitable combination of ligament and fulcrum system. The study provides an
      indication toward the desirable biomechanical properties of the fulcrum and
      ligament for future development of a clinically applicable prototype.

PMID- 15864155
TI  - Biomechanical analysis of a resorbable anterior cervical graft containment plate.
AB  - STUDY DESIGN: A series of in vitro experiments were performed in human cadaveric
      cervical spines in the normal condition, after discectomy and graft, and
      instrumented with MacroPore resorbable anterior plates (MacroPore, San Diego,
      CA). Flexibility, graft containment, and load-to-failure were studied. OBJECTIVE:
      To assess the stability, strength, and resistance to graft extrusion provided by
      the resorbable plate after discectomy and grafting. SUMMARY OF BACKGROUND DATA:
      Metallic plates are known to improve stability after discectomy and graft.
      Resorbable plates have not been evaluated regarding stability offered or ability
      to contain the graft. METHODS: Specimens were loaded using nonconstraining,
      nondestructive torques to induce flexion, extension, lateral bending, and axial
      rotation. One and 2-level specimens were studied: (1) normal, (2) after
      discectomy and graft, (3) after resorbable plating with 2 screws per vertebra,
      and (4) after resorbable plating with 3 screws per vertebra. All specimens were
      loaded to failure after completing nondestructive tests. Additional 1-level
      specimens with and without resorbable plate were tested for graft containment
      using anterior shear force directly on the graft. RESULTS: The 1-level resorbable
      plate did not limit motion significantly better than grafted but unplated
      specimens. However, 2-level resorbable plates allowed significantly less motion
      than grafted but unplated specimens during all loading modes (P < 0.05).
      Specimens with resorbable plates resisted graft extrusion significantly better
      than unplated specimens. With 1-level resorbable plates, 2 or 3 screws per
      vertebra provided equivalent stability; in 2-level plates, 3 screws provided
      significantly better stability. Comparison to previous 1-level metallic plate
      data revealed a significant difference in motion only during flexion.
      CONCLUSIONS: The 1-level resorbable plate does not increase stability compared to
      grafted but unplated specimens and provides less stability than a metal plate,
      especially during flexion. However, the resorbable plate substantially improves
      resistance to graft extrusion. The 2-level resorbable plate significantly reduces
      motion compared to grafted but unplated specimens. When applying a 2-level plate,
      3 screws per vertebra are recommended. In a 1-level plate, 2 or 3 screws per
      vertebra are equivalent.

PMID- 15864156
TI  - Proprioceptive recovery of patients with cervical myelopathy after surgical
      decompression.
AB  - STUDY DESIGN: A prospective observational study. OBJECTIVES: To determine whether
      proprioceptive deficit recovers after surgery and whether proprioceptive
      evaluation can predict functional outcome in cervical myelopathy patients.
      SUMMARY OF BACKGROUND DATA: Proprioceptive sensation plays an important role in
      smooth, coordinated movement of the limbs. Information about proprioception
      ascends through the dorsal columns in the spinal cord. In severe compressive
      myelopathy, proprioceptive ability would be reduced and could be improved after
      surgical decompression. However, there have been few studies concerning
      proprioceptive impairment in cervical myelopathy. MATERIALS AND METHODS: The
      study group included 26 cervical myelopathy patients who underwent posterior
      surgical decompression. Knee proprioception was assessed by joint position sense,
      which was evaluated by measuring the error angle when the subjects tried to
      reproduce the predetermined angle by extension and by flexion. Proprioceptive
      deficit in the study group was evaluated, compared with age-matched normal
      subjects. Postoperative recovery and correlation to functional status was
      analyzed in the study group. The Japanese Orthopedic Association (JOA) scores
      were used for functional evaluation. RESULTS: The error angles were significantly
      higher in the study group than those in the control group before surgery. All
      patients in the study group finally had improvement of the error angles by a year
      after surgery. The average of error angles in the study group was improved 2
      weeks after surgery; however, no changes were observed later. There was
      significant correlation between the improvement rate of the error angles 2 weeks
      after surgery and that of the JOA scores 2 years after surgery. There were 9
      patients who had worsened proprioception 2 weeks after surgery either by
      extension or by flexion, all of whom had poor functional outcome. CONCLUSIONS:
      Knee proprioception was impaired in cervical myelopathy and recovered after
      surgical posterior decompression. Proprioceptive improvement at 2 weeks
      correlates with the degree of improvement in JOA scores at 2 years after surgery.

PMID- 15864157
TI  - Design of cervical pedicle locator and three-dimensional location of cervical
      pedicle.
AB  - STUDY DESIGN: To develop a high-accuracy, easy-manipulated, and low-cost cervical
      pedicle three-dimensional locator for guiding cervical pedicle screw placement.
      OBJECTIVES: To improve the safety of cervical pedicle screw insertion, simplify
      its manipulation, and offer safety guarantees in clinical application. SUMMARY OF
      BACKGROUND DATA: Because of the complicacy of the anatomic structure of cervical
      pedicle, clinical application of cervical pedicle screw remained hard to
      popularize. And recent advances on cervical pedicle location did not simplify the
      manipulation of procedure significantly. Without aid of locator, distance and
      angle errors were difficult to control. So far, the only instrument for the
      location of pedicle "computer-assisted image-guided surgical system" is too
      expensive for clinical use. Furthermore, it has not yet been documented on
      location instrument for insertion of cervical pedicle screws. METHODS: The high
      accuracy three-dimensional locator, made of stainless steel was designed to aid
      cervical pedicle nail placement. The cadavers were inserted nails under guidance
      of the locator that has been input the corresponding parameters collected from CT
      images. Results were evaluated by CT scans. RESULTS: A total of 90 nails were
      inserted into cervical pedicles, 90% of which were found right in the pedicles;
      10% had pedicle cortex breaches. Parallel offset error of the locator in cross
      sectional and lateral CT image that was 0.56 +/- 0.70 and 1.04 +/- 0.99; angular
      offset error was 1.69 +/- 2.41 and 6.54 +/- 7.08. CONCLUSION: Three-dimensional
      locator of cervical pedicle and its localization technique achieved good results
      for individuated screws insertion into cervical pedicles, having such advantages
      as easy manipulation, high accuracy, and low cost. The system presented safety
      guarantee to the application and advanced the prevalence of pedicle techniques.
      Its principium and design were demonstrated feasible.

PMID- 15864158
TI  - The relationship of anticipated pain and fear avoidance beliefs to outcome in
      patients with chronic low back pain who are not receiving workers' compensation.
AB  - STUDY DESIGN: A prospective, interventional case series design. OBJECTIVES: To
      determine the degree to which preintervention measures of anticipated pain and
      fear avoidance beliefs predict outcome after intervention for patients with
      delayed recovery from low back pain (LBP) for which they are not receiving
      workers' compensation. SUMMARY OF BACKGROUND DATA: Anticipated pain and fear
      avoidance beliefs have been suggested as important factors for the classification
      and treatment of patients with LBP. However, the degree to which they are
      associated with outcome after intervention is uncertain. METHODS: There were 42
      subjects with activity limiting LBP for more than 2 months enrolled in an
      exercise based, physical therapy program. A multidimensional test battery was
      completed before and after a 10-week program of lumbar extensor muscle
      strengthening. Correlational analyses, independent t tests, and validity indexes
      were used to determine relationships of preintervention measures of anticipated
      pain and the fear avoidance beliefs to clinically meaningful improvements in the
      Roland-Morris score. Intention-to-treat strategies were used to account for study
      dropouts. RESULTS: A total of 36 subjects completed the 10-week intervention. The
      lack of clinically meaningful outcome, as determined by a failure-to-report a
      minimum of 16% decrease in the Roland-Morris score, was associated with high
      preintervention scores on the physical activity subscale of the Fear Avoidance
      Beliefs Questionnaire (FABQP). Subjects with a preintervention score > or =29 on
      the FABQP had a likelihood ratio of 3.78 (95% confidence interval [CI] 2.4-5.16)
      for an increased probability of negative outcome after initial testing when
      compared to those subjects with low (<20) scores. The sensitivity and specificity
      of low scores to predict clinically meaningful outcomes compared to those with
      high scores were moderate (sensitivity = 0.87 and specificity 0.77); however, the
      likelihood ratio was inconclusive. Anticipated pain was significantly correlated
      with but was higher than the reported pain during activity both before and after
      intervention but not predictive of outcome. CONCLUSIONS: In a sample of people
      from a Middle Eastern culture undergoing exercise intervention for LBP for which
      they are not receiving workers' compensation, the preintervention physical
      activity subscale of the FABQ is predictive of negative outcome when the observed
      scores are > or =29. Despite significant improvements in all variables after
      intervention, anticipated pain remained significantly higher than reported pain
      during physical performance testing but did not predict outcome.

PMID- 15864159
TI  - Perioperative changes in pulmonary function after anterior scoliosis
      instrumentation: thoracoscopic versus open approaches.
AB  - STUDY DESIGN: A prospective evaluation of pulmonary function in patients with
      adolescent idiopathic scoliosis undergoing surgical correction. OBJECTIVE: To
      determine if a minimally invasive thoracoscopic approach had less postoperative
      pulmonary function impairment compared to open anterior instrumentation for
      idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Prior studies suggest that open
      anterior scoliosis surgery causes an initial decrease in pulmonary function that
      resolves by 2 years after surgery. However, the effect of thoracoscopic
      instrumented scoliosis correction on pulmonary function is unknown. METHODS:
      Fifty-four patients with AIS undergoing anterior spinal instrumentation and
      fusion at the authors' institutions were evaluated with pulmonary function tests
      assessing forced vital capacity (FVC) and forced expiratory volume in one second
      (FEV1). Patients were evaluated before surgery,as well as 3 months and 1 year
      after surgery. There were 2 groups of patients: in one group, a thoracoscopic
      technique was used to visualize and instrument the anterior spine (n = 31); and
      in the other, an open single or double thoracotomy was used (n = 23). RESULTS:
      Three months after surgery, the thoracoscopic group had a significantly smaller
      decline in FVC than the thoracotomy group; at 1 year after surgery, the
      thoracoscopic group had recovered, while FVC remained reduced in the open group.
      The decline in FEV1 from before surgery to 3 months after surgery was similar
      between groups; however, by 1 year after surgery, the thoracoscopic group had
      more recovery of pulmonary flow than the thoracotomy group. CONCLUSIONS: The
      thoracoscopic approach causes a smaller decline in pulmonary function 3 months
      and 1 year after surgery as compared to the more invasive technique of open
      thoracotomy for anterior spinal instrumentation for correction of adolescent
      idiopathic scoliosis.

PMID- 15864160
TI  - Intra-observer reproducibility and interobserver reliability of the radiographic
      parameters in the Spinal Deformity Study Group's AIS Radiographic Measurement
      Manual.
AB  - STUDY DESIGN: Retrospective cross-sectional assessment of the reproducibility and
      reliability of radiographic parameters. OBJECTIVE: To measure the intra-examiner
      and interexaminer reproducibility and reliability of salient radiographic
      features. SUMMARY OF BACKGROUND DATA: The management and treatment of adolescent
      idiopathic scoliosis (AIS) depends on accurate and reproducible radiographic
      measurements of the deformity. METHODS: Ten sets of radiographs were randomly
      selected from a sample of patients with AIS, with initial curves between 20
      degrees and 45 degrees. Fourteen measures of the deformity were measured from
      posteroanterior and lateral radiographs by 2 examiners, and were repeated 5 times
      at intervals of 3-5 days. Intra-examiner and interexaminer differences were
      examined. The parameters include measures of curve size, spinal imbalance,
      sagittal kyphosis and alignment, maximum apical vertebral rotation, T1 tilt,
      spondylolysis/spondylolisthesis, and skeletal age. RESULTS: Intra-examiner
      reproducibility was generally excellent for parameters measured from the
      posteroanterior radiographs but only fair to good for parameters from the lateral
      radiographs, in which some landmarks were not clearly visible. Of the 13
      parameters observed, 7 had excellent interobserver reliability. CONCLUSIONS: The
      measurements from the lateral radiograph were less reproducible and reliable and,
      thus, may not add value to the assessment of AIS. Taking additional measures
      encourages a systematic and comprehensive assessment of spinal radiographs.

PMID- 15864161
TI  - Test-retest reliability of the Progressive Isoinertial Lifting Evaluation (PILE).
AB  - STUDY DESIGN: A repeated measures single group design. OBJECTIVES: To investigate
      test-retest reliability of Progressive Isoinertial Lifting Evaluation on patients
      with long lasting musculoskeletal problems related to the lumbar spine. SUMMARY
      OF BACKGROUND DATA: Test-retest reliability has been satisfactory in healthy men.
      Test-retest reliability for clinical populations has not been reported. METHODS:
      A total of 31 patients (17 women and 14 men) with long lasting low back pain
      participated in the study. The patients were tested twice at an interval of 2
      days and at the same time of the day. The heaviest load that the patient could
      lift 4 times was used as outcome measure. RESULTS: The error of measurement
      indicates that the true result in 95% of cases will be within +/-4.5 kg from the
      measured value, while the difference between 2 measurements in 95% of cases will
      be less than 6.4 kg. Intra-class correlation (1,1) was 0.91. CONCLUSIONS:
      Relative test-retest reliability was high assessed by intra-class correlation,
      but absolute measurement variability reported as the smallest detectable
      difference has relevance for the interpretation of clinical test results and
      should also be considered.

PMID- 15864162
TI  - Analgesic usage for low back pain: impact on health care costs and service use.
AB  - STUDY DESIGN: Cross-sectional analysis of analgesic use by patients with low back
      pain (LBP). OBJECTIVES: To describe patterns of analgesic use and their cost
      implications for the use of other care services among individuals with LBP
      enrolled in a health insurance plan during 2001. It was hypothesized that the use
      of analgesics would be most frequent among patients with LBP with neurologic
      findings. SUMMARY OF BACKGROUND DATA: National guidelines have recommended
      analgesics as the primary pharmacologic treatment of LBP. The choice of specific
      analgesics has major cost and service use implications. METHODS: The University
      of Pittsburgh Health System includes 18 affiliated hospitals, more than 5000
      physicians, and a commercial health plan with 255,958 members in 2001. This study
      uses the System Health Plan's insurance claims database to identify members who
      had services provided for one of 66 International Classification of Diseases,
      Version 9, Clinical Modification codes that identify mechanical LBP (n = 17,148).
      RESULTS: In 2001, 7631 (43.5%) members with claims for LBP services had no
      analgesic pharmacy claims. The other 9517 (55.5%) had analgesics claims costing a
      total of $1.4 million; 68% of claimants were prescribed an opioid and 58%
      nonselective nonsteroidal antiinflammatory drugs (NSAID). The costs of opioids,
      NSAID, and cyclooxygenase-2 selective NSAID for patients with LBP represented
      48%, 24%, and 28%, respectively, of total health plan expenditures for all uses
      of these drugs, including cancer. Opioid use was associated with the high volume
      usage of LBP care services. Patients with LBP with and without neurologic
      involvement and those with acquired lumbar spine structural disorders had similar
      patterns of analgesic use: those with congenital structural disorders were less
      likely to use analgesics; and those with psychogenic pain and LBP related to
      orthopedic devices were more likely to use opioids. CONCLUSIONS: With this health
      plan, a high proportion of patients with LBP had claims for opioids during 2001.
      The use of opioids by patients with LBP represents a major cost for the health
      plan, and is associated with specific patient characteristics and their use of
      other LBP services.

PMID- 15864163
TI  - Adult scoliosis: prevalence, SF-36, and nutritional parameters in an elderly
      volunteer population.
AB  - STUDY DESIGN: A prospective self-assessment analysis and evaluation of
      nutritional and radiographic parameters in a consecutive series of healthy adult
      volunteers older than 60 years. OBJECTIVES: To ascertain the prevalence of adult
      scoliosis, assess radiographic parameters, and determine if there is a
      correlation with functional self-assessment in an aged volunteer population.
      SUMMARY OF BACKGROUND DATA: There exists little data studying the prevalence of
      scoliosis in a volunteer aged population, and correlation between deformity and
      self-assessment parameters. METHODS: There were 75 subjects in the study.
      Inclusion criteria were: age > or =60 years, no known history of scoliosis, and
      no prior spine surgery. Each subject answered a RAND 36-Item Health Survey
      questionnaire, a full-length anteroposterior standing radiographic assessment of
      the spine was obtained, and nutritional parameters were analyzed from blood
      samples. For each subject, radiographic, laboratory, and clinical data were
      evaluated. The study population was divided into 3 groups based on frontal plane
      Cobb angulation of the spine. Comparison of the RAND 36-Item Health Surveys data
      among groups of the volunteer population and with United States population
      benchmark data (age 65-74 years) was undertaken using an unpaired t test. Any
      correlation between radiographic, laboratory, and self-assessment data were also
      investigated. RESULTS: The mean age of the patients in this study was 70.5 years
      (range 60-90). Mean Cobb angle was 17 degrees in the frontal plane. In the study
      group, 68% of subjects met the definition of scoliosis (Cobb angle >10 degrees).
      No significant correlation was noted among radiographic parameters and visual
      analog scale scores, albumin, lymphocytes, or transferrin levels in the study
      group as a whole. Prevalence of scoliosis was not significantly different between
      males and females (P > 0.03). The scoliosis prevalence rate of 68% found in this
      study reveals a rate significantly higher than reported in other studies. These
      findings most likely reflect the targeted selection of an elderly group. Although
      many patients with adult scoliosis have pain and dysfunction, there appears to be
      a large group (such as the volunteers in this study) that has no marked physical
      or social impairment. CONCLUSIONS: Previous reports note a prevalence of adult
      scoliosis up to 32%. In this study, results indicate a scoliosis rate of 68% in a
      healthy adult population, with an average age of 70.5 years. This study found no
      significant correlations between adult scoliosis and visual analog scale scores
      or nutritional status in healthy, elderly volunteers.

PMID- 15864164
TI  - Health status, its perceptions, and effect on return to work and recurrent sick
      leave.
AB  - STUDY DESIGN: Prospective cohort study with 1-year follow-up. OBJECTIVES: The
      purpose of this study is to describe the improvement in several health outcomes
      during sick leave resulting from musculoskeletal disorders and in the first
      months after return to work (RTW), and to evaluate the personal and work-related
      factors associated with these health outcomes, in order to provide some insight
      in the timing of RTW. SUMMARY OF BACKGROUND DATA: Although improvements in pain
      perception and functional disability appear to be associated with time of RTW,
      little is known about the required improvement enabling RTW, the additional
      health improvement after RTW, and whether the health status at the time of RTW is
      associated with the probability of a recurrence of sick leave. METHODS: Workers
      were included when on sickness absence between 2 to 6 weeks due to
      musculoskeletal disorders. Self-administered questionnaires at baseline, after
      RTW, and at 12-month follow-up were used to collect information on changes in
      symptom status, functional status, and general health. RESULTS: All health
      outcomes were improved significantly at the time of RTW, whereas perceived pain,
      functional disability, and physical health also improved significantly in the
      first months after RTW. Previous sick leave 12 months before study entry was
      significantly associated with the level of functional disability and general
      health at time of RTW and also predictive for recurrence of sickness absence.
      Personal and work-related factors showed little, if any, association with health
      status at RTW and improvement thereafter. CONCLUSIONS: Being fully recovered is
      not a stipulation for regaining work activities. We hypothesize that workers with
      musculoskeletal disorders may need additional medical guidance shortly after RTW,
      especially those with a history of sick leave.

PMID- 15864165
TI  - Prevalence of low back pain in a developing urban setting.
AB  - STUDY DESIGN: A cross-sectional survey was conducted using face-to-face
      interviews. OBJECTIVES: To estimate the prevalence of low back pain (LBP) in an
      urban population of Turkey and to determine the factors associated with
      occurrence of LBP. SUMMARY OF BACKGROUND DATA: Little information exists in the
      literature regarding the epidemiology of LBP in developing countries. A few data
      from previous studies suggest that the prevalence of LBP is rather lower in
      developing countries compared with developed countries. METHODS: A total of 100
      clusters of households (3,215 residents aged 16 years or older) in municipality
      area of Antalya was selected by systematic sampling. Of these, 3,173 study
      participants agreed to interview. The response rate was 98.7%. RESULTS: The crude
      lifetime, 12-month, and point prevalences of LBP were 46.6% (95% confidence
      interval [CI], 44.9-48.3), 35.9% (95% CI, 34.2-37.6), and 20.1% (95% CI, 18.7
      21.5), respectively. In logistic regression analysis, age of 36 years or older,
      female sex, multiparity, being a housewife, being from East Turkey, and smoking
      showed independent associations with having current LBP. Being religious, heavy
      smoking, and age 26 to 45 years were associated with having restricted activity
      related to LBP. CONCLUSIONS: In comparison with other developing countries, point
      prevalence of LBP is higher in Turkey and approximates to prevalence estimates of
      LBP in developed countries. Smoking may be associated with both occurrence and
      severity of LBP. Although piety is not associated with having LBP, religious
      people are more likely to have restricted activity related to LBP.

PMID- 15864166
TI  - Industry support and correlation to study outcome for papers published in Spine.
AB  - STUDY DESIGN: Retrospective review of articles published in the journal Spine.
      OBJECTIVES: To evaluate potential correlations between research sponsorship and
      study outcome. SUMMARY OF BACKGROUND DATA: Industry sponsorship has traditionally
      been associated with more positive results than non-funded or peer-reviewed
      funded projects in other areas of medicine. The association of such sponsorship
      and study outcome has not been addressed previously in spine research. METHODS:
      Articles from the journal Spine from January 2002 to July 2003 were reviewed.
      These were examined for the subject evaluated, type of study design, funding
      source, and conclusion reached. RESULTS: Of 1143 articles, 527 met inclusion
      criteria of having abstract, materials/methods, and conclusion sections. Industry
      support was reported for 84 (15.9%), foundation support for 67 (12.7%),
      government support for 54 (10.2%), institution support for 17 (3.2%), and no
      funding was reported for 304 (57.9%). The odds ratio of industry funded reporting
      positive results was 3.3 times that of studies with any other funding sources (P
      < 0.001). CONCLUSIONS: Industry funded studies demonstrated a statistically
      greater likelihood to report positive results than studies with other funding
      sources. Potential explanations for this are biased study design, biased
      experimental technique, biased result interpretation, or publication bias.
      Although the expense of research and limited funding sources have forced an
      increased reliance on industry support for funding basic science and clinical
      spine research, this does introduce the potential for bias and must be recognized
      by the reader.

PMID- 15864169
TI  - Are children's backpack weight limits enough? A critical review of the relevant
      literature.

PMID- 15864170
TI  - [Editorial track record for 2004].

PMID- 15864171
TI  - Efficacy of intravenous cyclosporin in moderately severe ulcerative colitis
      refractory to steroids.
AB  - OBJECTIVE: The efficacy of intravenous cyclosporin (CSA) in acute severe
      ulcerative colitis (UC) is well established. The aim of this study was to
      evaluate its efficacy in moderately severe colitis refractory to steroids.
      METHODS: Twenty-six patients (17 men, mean age 41 +/- 14 yr) with UC refractory
      to steroids treated with CSA were included in this study. Severity was defined
      according to Truelove criteria. A clinical activity score below 10 during 2
      consecutive days defined clinical response. RESULTS: According to Truelove
      criteria, all patients had moderate UC. CSA was administered IV at a mean daily
      dose of 3.7 +/- 0,5 mg/kg until response and then orally for 3.5 +/- 2.6 months.
      A clinical response was achieved in 20/26 patients (76,9%) within 5.7 +/- 2.8
      days (5/6 failures were treated by proctocolectomy). During a follow-up of 27.8
      +/- 20.8 months, relapse rate was 60% (12/20): 7 patients underwent
      proctocolectomy and 5 had clinical remission with CSA retreatment (N=4) and
      steroids (N=1). At the end of follow-up, 12 patients (46%) were in clinical
      remission, 12 (46%) required colectomy, 1 had chronic active UC and 1 was lost of
      follow-up. The probability to avoid surgery was 52% at 78 months. The only factor
      associated with avoidance of surgery was concomitant treatment with azathioprine
      (P=0.007). Ten reversible adverse events occurred in 9 patients. CONCLUSION: This
      study shows that CSA is safe and effective in moderately severe steroid resistant
      UC. Concomitant treatment with azathioprine significantly decreases the rate of
      subsequent surgery. CSA may act as a "bridge" until the therapeutic action of
      azathioprine is achieved for maintenance treatment. These results should be
      further confirmed by a prospective controlled study.

PMID- 15864172
TI  - Hemosuccus pancreaticus: a rare cause of gastrointestinal bleeding.
AB  - AIM: The purpose of this study was to analyze the diagnostic and therapeutic
      features of hemosuccus pancreaticus. METHODS: We conducted a retrospective study
      of nine patients (eight men and one woman, mean age 60 yrs) admitted to surgery
      or gastroenterology units for hemossucus pancreaticus between 1981 and 2003. The
      following were studied: symptoms, contribution of established morphologic exams
      (upper digestive endoscopy, computed tomography (CT) and selective digestive
      angiography) and treatment. RESULTS: Hemosuccus pancreaticus occurred in chronic
      alcoholic pancreatitis (N=8) and chronic familial pancreatitis (N=1). Seven
      patients (77.8%) presented overt digestive bleeding (one melena, two
      hematochezia, two melena with hematochezia, one hematemesis, one hemorrhagic
      shock). The inaugural sign was anemia in one patient and epigastric pain in
      another. An upper digestive endoscopy, performed in eight patients (88.9%),
      revealed fresh red blood in the first or second duodenum in three and hemossucus
      pancreaticus in three others. Arteriography was performed in eight patients
      (88.9%) and CT angiography in one. Surgery was performed in 5 patients (55.6%),
      after embolization in one. Embolization was effective in 3 patients. Therapeutic
      abstention proved successful in one patient. There were no deaths. CONCLUSIONS:
      Hemosuccus pancreaticus is a rare cause of digestive bleeding. Upper digestive
      endoscopy and selective digestive angiography during active bleeding can provide
      the diagnosis. Endovascular treatment can control an unstable hemodynamic
      situation before elective surgery to prevent recurrence, which can be more severe
      than the first event.

PMID- 15864173
TI  - Prevalence of functional gastrointestinal disorders in a population of subjects
      consulting for gastroesophageal reflux disease in general practice.
AB  - AIMS: To establish the prevalence of functional gastrointestinal (GI) disorders
      in adult patients with symptoms of gastroesophageal reflux disease (GERD) and to
      assess the impact of GERD treatment on functional GI disorders in medical
      practice in France. METHODS: 3318 patients with GERD symptoms (mean age 53 yr;
      1726 women and 1592 men) were involved in the survey. A questionnaire on
      demographic data, GERD features, presence of functional GI disorders and their
      features, and impact of GERD treatment on functional GI disorders was performed
      by the physician. The size of the different groups was compared using either a
      chi2 test or a Mantel-Haenszel analysis, on a case by case basis. RESULTS:
      Seventy-two percent of patients with GERD had associated functional GI disorders,
      with a mean of 4.1 +/- 1.9 functional digestive symptoms per patient. Gas,
      flatulence, transit disorders and abdominal distension were the most commonly
      reported symptoms. Among patients with functional GI symptoms, 27% had symptoms
      suggestive of irritable bowel syndrome (IBS), 16% were suggestive of dyspepsia
      while 57% had both upper and lower functional digestive symptoms. According to
      the patients, GERD treatment had a positive impact (significant to complete
      improvement) on their functional GI disorders in about one-third of patients
      particularly in those with dyspeptic-type symptoms. CONCLUSIONS: Functional GI
      disorders are particularly common in adult patients suffering from GERD, with a
      three times higher prevalence than in the general population.

PMID- 15864174
TI  - Factors contributing to infectious diarrhea-associated pancreatic enzyme
      alterations.
AB  - OBJECTIVES: Several pathogens have been involved as etiologic agents of acute
      pancreatitis. We studied 59 patients presenting acute infectious diarrhea in
      order to determine the incidence as well as to identify factors which may
      contribute to the occurrence of pancreatic enzyme alteration or true acute
      pancreatitis. METHODS: Patients were evaluated for serum lipase and amylase, and
      24-hours urinary amylase. Clinical and biological parameters were noted.
      Abdominal sonography and rectosigmoidoscopy were performed. RESULTS: Pancreatic
      enzyme alteration was found in 24% of patients. Twelve had salmonellosis and 2
      Campylobacter jejuni infection. They had more prolonged diarrhea, more frequent
      renal impairment and increased triglyceridemia. Triglyceridemia was correlated to
      blood amylase, inflammatory syndrome and renal impairment. Serum amylase was
      linked to serum urea and creatinine and to biological markers of inflammation.
      Three patients had true acute pancreatitis. CONCLUSION: Patients presenting
      dysentery-like infectious diarrhea and upper abdominal pain should be
      investigated for concomitant pancreatic reaction or acute pancreatitis which
      seems more frequent in patients with enterocolitis due to enteroinvasive
      microbes, mostly non-typhoidal Salmonella. Pancreatic disturbances are related to
      the severity of these infections. However, overt infectious diarrhea-associated
      pancreatitis is a rare event.

PMID- 15864175
TI  - [Food and digestive allergies in adults].

PMID- 15864176
TI  - [Several good reasons for hepatogastroenterologists to practice addictology: a
      motivating challenge!].

PMID- 15864177
TI  - Balance between pro and anti-inflammatory cytokines in patients with acute
      alcoholic hepatitis.
AB  - The ability of endogenous IL-10 to modulate inflammatory response and to limit
      hepatotoxicity has been shown in several models of liver injury. AIMS: The
      objectives of this study were to evaluate the relationship between liver disease
      and the balance between pro and anti-inflammatory cytokines in acute alcoholic
      hepatitis. METHODS: Twenty-five patients with pure steatosis, 17 with cirrhosis
      and mild acute alcoholic hepatitis (discriminant function value<32) and 41
      patients with cirrhosis and severe acute alcoholic hepatitis (discriminant
      function value >=32) were studied. Plasma levels of interleukin 10 (IL-10) and
      soluble TNF receptors (TNFsRp75 and 55) were analyzed using ELISA assays.
      Hepatocyte proliferative activity was assessed with proliferating cell nuclear
      antigen labeling index (PCNA-LI) on formalin-fixed paraffin embedded liver biopsy
      specimens. RESULTS: In patients with steatosis, cirrhosis with mild and severe
      acute alcoholic hepatitis, the plasma levels of IL-10 were higher (P<0.05) than
      in healthy controls. Between day 1 and day 8, the TNFsRp55/IL-10 ratio increased
      by 137 +/- 47 in the 10 patients with severe acute alcoholic hepatitis treated
      with prednisolone who died within 2 months and by 9.3 +/- 14 in the 19 patients
      still alive at 2 months (P=0.031). In patients with severe acute alcoholic
      hepatitis, PCNA-LI on liver biopsy was negatively correlated with the TNFsRp55/IL
      10 ratio increase from day 1 to day 8 (r=- 0.42, P=0.11). PCNA-LI was positively
      correlated with TNFsRp75/TNFsRp 55 ratio increase from day 1 to day 15 (r=0.52;
      p<0.05). CONCLUSION: Our data suggest the anti-inflammatory system is up
      regulated in patients with alcoholic liver disease. Nevertheless, in patients
      with severe acute alcoholic hepatitis, IL-10 production seems insufficient to
      modulate TNF-alpha cytotoxicity mediated by TNFRp55.

PMID- 15864178
TI  - Usefulness of routine analysis of ascitic fluid at the time of therapeutic
      paracentesis in asymptomatic outpatients. Results of a multicenter prospective
      study.
AB  - AIM: The guidelines of the American Association for the Study of Liver Diseases
      recommend performing exploratory paracentesis on each patient with cirrhosis and
      chronic ascites. The aim of the study was to evaluate the prevalence of
      spontaneous bacterial peritonitis and culture-negative neutrocytic ascites in a
      large population of consecutive asymptomatic cirrhotic ascitic ambulatory
      patients. METHODS: Patients with cirrhosis and tense ascites hospitalized from
      January to September 2000 in 5 hepatogastroenterology units prospectively
      underwent an exploratory paracentesis with cytobacteriological, biochemical and
      bedside inoculation into aerobic and anaerobic blood culture bottles. Patients
      studied were not receiving antibiotics except for norfloxacin and had no obvious
      sign of infection such as fever or hypothermia, chills, unusual abdominal
      tenderness, de novo or worsening hepatic encephalopathy, recent gastrointestinal
      bleeding, acute renal failure or marked arterial hypotension. Clinical and
      biological findings and ascitic fluid cytological and bacteriological results
      were evaluated at each exploratory paracentesis. The results are given in mean +/
      standards deviations with range. RESULTS: Sixty-seven cirrhotic patients
      (48M/19F, mean age 59 +/- 9 years) had 270 therapeutic paracenteses, preceded by
      an exploratory aspiration. Fifty-nine patients (88%) had alcoholic cirrhosis.
      Twenty-five patients (37.3%) received norfloxacin. At first paracentesis 41
      (61.2%) and 26 (38.8%) patients were class B and C respectively according to the
      Child-Pugh classification; the mean Child-Pugh score was 9 +/- 1.5. None had
      suspicion of infection. The mean number of paracenteses was 5 +/- 4.3 per
      patient; 59.6% of the paracenteses (161) were compensated with human albumin.
      Ascitic protein concentration was 17.5 +/- 8.6 g/l, ascitic fluid cell count and
      number of neutrophils were 127 +/- 155/mm3 and 5.9 +/- 14/mm3 (0-60),
      respectively. No patient had spontaneous bacterial peritonitis nor culture
      negative neutrocytic ascites; 10 cases of monomicrobial bacterascites were
      observed, all with commensal germs. CONCLUSIONS: In the absence of obvious signs
      of infection, the prevalence of spontaneous bacterial peritonitis and culture
      negative neutrocytic ascites in asymptomatic cirrhotic outpatients with ascites
      is near 0%. Moreover, for 100 large volume paracenteses, not performing
      exploratory paracentesis corresponds to a savings of 5,500 euros, without risk
      for these patients.

PMID- 15864179
TI  - [Effects of bariatric surgery on the liver].

PMID- 15864180
TI  - [Rectal Abrikossof tumor: a rare location].
AB  - Granular cell tumors or Abrikossof tumors are neurogenous ubiquitary submucosal
      like tumors that are usually benign. The most frequent locations are the skin and
      buccal cavity. The usual location in the digestive tract is the esophageal wall.
      We report a rare case of Abrikossof tumor of the rectum that was not operated on
      because of a certain diagnosis and a low risk of malignancy.

PMID- 15864181
TI  - [Pseudopapillary tumor of the pancreas revealed by rupture of esophageal and
      gastric varices secondary to biliary cirrhosis due to bile duct compression].
AB  - Pseudo-papillary tumors of the pancreas are rare and usually occur in young
      women. We report a case with a very rare presentation (rupture of esogastric
      varices complicating biliary cirrhosis secondary to bile duct compression by a
      pancreatic tumor). After biological and radiological explorations, a
      duodenopancreatectomy was performed. Diagnosis was confirmed by conventional
      histology and immunohistochemistry. One year later, the patient remained
      asymptomatic.

PMID- 15864182
TI  - [Acute pancreatitis revealing Behcet disease].
AB  - We report here a case of acute pancreatitis revealing Behcet's disease in an 18
      year-old woman. Pancreatitis was due to ischemia secondary to severe
      abnormalities of the celiac trunk arteries with pseudo-aneurysms. The outcome was
      favourable after the administration of corticosteroids and cyclophosphamide. The
      patient did not experience relapse of pancreatitis 2 years after diagnosis.

PMID- 15864183
TI  - [Severe autoimmune neutropenia and thrombopenia associated with chronic C
      hepatitis: effect of antiviral therapy].
AB  - We report the case of a 45-year-old man admitted for severe autoimmune
      thrombopenia and neutropenia associated with chronic viral C hepatitis. After
      failed, intravenous gammaglobulin and corticosteroid therapy antiviral treatment
      with interferon and ribavirin was given for one year. Thrombopenia improved
      progressively during antiviral therapy and worsened after the end of treatment.
      Neutropenia improved during antiviral therapy. Two years after the end of
      treatment, serum RNA-HCV was positive, white cell count was normal and platelet
      count was 77 G/L. In conclusion, these results suggest that antiviral therapy may
      be useful in patients with auto-immune cytopenia associated with viral hepatitis
      C infection.

PMID- 15864184
TI  - [Langerhans cell histiocytosis in an adult patient associated with sclerosing
      cholangitis and cerebellar atrophy].
AB  - Langerhans' cell histiocytosis is a disorder in children or young adults,
      characterized by clonal proliferation of histiocytic cells, staining for CD1a,
      with uni or multifocal organ involvement. It's a rare condition in adults. We
      report a case of Langerhans' cell histiocytosis in an adult with sclerosing
      cholangitis which rapidly progressed to fatal liver failure and progressive
      cerebellar atrophy. Langerhans cell histiocytosis is a rare cause of sclerosing
      cholangititis in adults.

PMID- 15864185
TI  - [Severe ischemic colitis after administration of Rhinadvil in a fifteen year old
      girl].

PMID- 15864186
TI  - [Endocrine pancreatic tumor after radiotherapy induced chronic pancreatitis].

PMID- 15864187
TI  - [Median pancreatectomy for early glucagonoma].

PMID- 15864188
TI  - [Candida cholecystitis: an unusual complication of endoscopic retrograde
      cholangiopancreatography].

PMID- 15864189
TI  - [Ascites revealing a multiple myeloma complicated by AL amyloidosis].

PMID- 15864190
TI  - [Confocal endoscopy].

PMID- 15864191
TI  - [Prognostic value of a unique measurement of the hepatic venous pressure
      gradient: who, when and why?].

PMID- 15864192
TI  - Risk factors and long-term course of thyroid dysfunction during antiviral
      treatments in 221 patients with chronic hepatitis C.
AB  - AIM: To identify the predictive factors of dysthyroidism during treatment for
      chronic viral hepatitis C and to evaluate the long-term outcome of these
      patients. METHODS: Patients treated for chronic viral hepatitis C between 1990
      and 2001 were analyzed retrospectively. Patients with dysthyroidism before
      treatment and patients positive for hepatitis B surface antigen or human
      immunodeficiency virus antibodies were excluded. Dysthyroidism was defined by an
      abnormal serum TSH level on two separate occasions. RESULTS: 221 consecutive
      patients were included. Among them, a hundred were treated twice by interferon
      alpha, 21 had 3 treatments and 3 had 4 treatments. Fifteen of these patients (7%)
      had dysthyroidism during antiviral therapy. There was no significant difference
      in the frequency of dysthyroidism during the first and the second treatment
      [respectively 4,1% (N = 9) and 6% (N = 6)]. Female gender and the presence of
      antimicrosome or antithyroperoxydase (anti-TPO) antibodies before antiviral
      treatment were predictive factors of dysthyroidism. Treatment by interferon and
      ribavirin did not increase the risk of dysthyroidism compared to monotherapy with
      interferon. Pegylated interferon (N = 49) was not a risk factor compared to
      standard interferon. Thirteen patients had hypothyroidism (2 of them as a result
      of biphasic thyroiditis) and 2 had hyperthyroidism. The antiviral treatment was
      continued in 11 patients. Seven out of 13 patients with hypothyroidism required
      an indefinite treatment (follow-up: 15 to 90 months). CONCLUSIONS: In our series,
      7% of patients with chronic viral hepatitis C had a dysthyroidism during
      antiviral therapy. Predictive factors were female gender and positive
      antimicrosome or anti-TPO antibodies before treatment. Absence of dysthyroidism
      during a first antiviral treatment did not preclude from the risk of
      dysthyroidism during a second treatment.

PMID- 15864193
TI  - Serum albumin and platelet count but not portal pressure are predictive of death
      in patients with Child-Pugh A hepatitis C virus-related cirrhosis.
AB  - AIM: The presence of esophageal varices has been reported to be a prognostic
      factor in patients with compensated hepatitis viral C induced cirrhosis. We
      studied the prognostic value of hepatic venous pressure gradient in addition to
      epidemiological and clinical parameters in these patients. METHODS: Among
      patients with Child-Pugh A hepatitis C induced cirrhosis, prospectively followed
      in two Parisian centres, 100 had measurement of occluded and free hepatic venous
      pressures. We evaluated hepatic venous pressures as a predictive factor of death
      by Cox models (survival) and Fine and Gray models (liver-deaths). RESULTS: Median
      hepatic occluded pressure and gradient were 21.5 (15-24) and 13 mm Hg (9-15),
      respectively. The median duration of follow-up was 85 months (range: 70-112); 38
      deaths or liver transplantation were registered. Hepatic venous pressure gradient
      was not significantly related to survival in the studied population but as a
      continuous variable was predictive of death from liver disease. On multivariable
      analysis serum albumin <40 g/L and platelet count <90,000 /mm(3) were the only
      selected prognostic factors. CONCLUSION: Hepatic venous pressure gradient has a
      limited value for assessing the prognosis of patients with Child-Pugh A hepatitis
      C virus induced cirrhosis; prognosis is accurately predicted by serum albumin and
      platelet count.

PMID- 15864194
TI  - [Drug-induced pancreatitis. Second edition of the bibliographic database of
      pancreatitis related to drugs].

PMID- 15864196
TI  - [What tests should be prescribed in HBs-positive patients].

PMID- 15864197
TI  - [Inactive carrier of hepatitis B virus].

PMID- 15864198
TI  - [Chronic hepatitis B: which patients should be treated and how?].

PMID- 15864199
TI  - [Treatment of delta (type D) hepatitis].

PMID- 15864200
TI  - [Hepatitis B vaccine after the 2003 consensus conference].

PMID- 15864201
TI  - [Prevention and treatment of hepatitis B virus infection after liver
      transplantation].

PMID- 15864204
TI  - [NSAID, type 2 cyclo-oxygenase inhibitors and pancreatic carcinogenesis].

PMID- 15864205
TI  - Management of surgical complications of small-bowel diverticulosis.
AB  - INTRODUCTION: Diagnosis of complications of small bowel diverticulosis is
      difficult in the emergency setting and often delays surgical management. The aim
      of this study was to report our experience with seven patients presenting with a
      surgical complication of small-bowel diverticulosis. PATIENTS AND METHODS: From
      January 1, 1995 to June 30, 2001, 7 patients presenting with a complication of
      small-bowel diverticulosis were included in this retrospective study. The mean
      age of the patients was 73.1 years. Complications were bleeding in 4 cases and
      diverticulitis with perforation and abscess formation in 3 cases. RESULTS: The
      time between complication onset and its management was 20.6 days. Among
      paraclinical examinations small-bowel barium opacification showed diverticulosis
      in 4 cases. Other investigations such as endoscopy or CT-Scan imaging studies
      were used to eliminate other causes of acute abdomen. Patients were operated on
      in all cases and a segmental small bowel resection was performed in all cases
      while in one patient, a diversion stomy was performed. One patient died following
      septic peritonitis treatment. CONCLUSION: Small-bowel diverticulosis is
      unfrequent. In cases of gastrointestinal haemorrhage or occlusion, diagnosis is
      performed by eliminating other more frequent causes. If emergency surgery is not
      required, barium opacification seems to be the most sensitive examination.

PMID- 15864206
TI  - Gastrointestinal tuberculosis: 17 cases collected in 4 hospitals in the
      northeastern suburb of Paris.
AB  - Gastrointestinal tuberculosis is a rare form of extrapulmonary tuberculosis and
      its diagnosis can be difficult. AIMS: To analyze the diagnostic and therapeutic
      characteristics of gastrointestinal tuberculosis. METHODS: Retrospective study
      from 17 cases collected in 4 hospitals in Seine Saint-Denis between 1987 and
      2002. RESULTS: Seventeen cases and 19 localizations were collected: small
      intestine (N = 7), ileocecum (N = 6), colon (N = 4) and gastroduodenum (N = 2).
      Two patients had two localizations. Mean age was 43.9 years. Subjects from
      immigrant populations (76.5%) were preferentially affected. Twenty-three percent
      of patients (13 tested) were infected by human immunodeficiency virus. Weight
      loss and general weakness (88%), abdominal pain (88%), fever (59%),
      nausea/vomiting (53%) were the predominant symptoms. The delay in diagnosis was
      82 days (range: 7-180) and time before specific treatment 31.6 days (range: 7
      90). Histological evidence of caseating granuloma was found in six patients.
      Mycobacterium tuberculosis was detected in six. Digestive imaging was abnormal in
      15 patients. Mesenteric lymph nodes were the most common associated site of
      tuberculosis (N = 8, 47%). Mean duration of treatment was 8.2 months (range: 6
      12). Thirteen patients were cured, three died and one was lost to follow up.
      CONCLUSION: Gastrointestinal tuberculosis is not an uncommon diagnosis in the
      north-eastern Parisian area, especially among immigrant populations and
      immunodeficient patients. The most frequent localizations are the small intestine
      and ileocecum. Diagnosis can be made by pathology and/or bacteriology on
      endoscopic and/or surgical biopsy samples.

PMID- 15864207
TI  - Secondary implantation of an artificial sphincter after abdominoperineal
      resection and pseudocontinent perineal colostomy for rectal cancer.
AB  - INTRODUCTION: Fecal continence with a perineal colostomy performed after
      abdominoperineal resection (APR) is not always satisfactory despite retrograde
      colonic enemas. Functional improvement is currently examined using artificial
      sphincters. Preliminary results are disclosed. PATIENTS: In 3 female patients,
      45, 59 and 68 years old, curative APR and perineal colostomy were performed after
      radiotherapy in 2, for T1-2N0 cancer of the lower rectum. Due to occasional
      leaks, need for strict diet and fear of incontinence, an Acticon Neosphincter
      (AMS) was implanted consecutively at a mean 4.5 years after APR. RESULTS: Device
      implantation was feasible and uneventful. In one case, a superficial hematoma was
      drained and healed by second intention. Devices were activated 3 months after
      implantation. At a mean 2.5 years follow-up, the 3 patients had an activated and
      functional artificial sphincter. Leaks and fecal urgency significantly decreased
      but colonic enemas were maintained. Dietary restrictions were less and quality of
      life improved. All 3 considered the device as a useful adjunct. CONCLUSION: In
      this limited experience, implantation of artificial sphincter around a perineal
      colostomy following APR for rectal cancer appeared feasible and safe even in case
      of previous radiotherapy. Mid-term tolerance was satisfactory. Continence and
      quality of life significantly improved.

PMID- 15864208
TI  - Complications of stapled hemorrhoidectomy: a French multicentric study.
AB  - OBJECTIVES: The aim of this retrospective multicentric study was to assess the
      complications of the Longo technique for the treatment of haemorrhoidal disease.
      METHODS: From March 1999 to April 2003, 550 patients underwent a stapled
      hemorrhoidectomy following Longo's technique in 12 surgical units in the Rhone
      Alpes Region. The operative indications were the same as for conventional
      hemorrhoidectomy. Complications were divided into early or late complications
      depending on whether they occurred before or after the 7th day. For each patient,
      the most serious complication was retained for analysis. RESULTS: One hundred and
      five patients (19%), mean age 51 years, experienced complications. The early
      complications were bleeding (1.8%), severe anal pain (2.3%), urinary retention
      (0.9%) and sepsis (0.5%). Late complications were chronic anal pain (1.6%),
      suture dehiscence (1.6%), anal stricture (1.6%), anal fissure (0.9%), external
      thrombosis (0.9%), fistulae and intramural abscesses (0.9%), anal incontinence
      (0.3%), haemorrhoidal disease symptoms persistence or recurrence (3.2%).
      Strictures were successfully dilated, fissures were treated by sphincterotomy,
      external thromboses were excised and fistulae were laid open. Most of the
      recurrences were treated with the Milligan-Morgan hemorroidectomy technique.
      CONCLUSION: Complications may occur after stapled hemorrhoidopexy, some are
      particularly serious, especially bleeding and sepsis.

PMID- 15864209
TI  - [Matrix metalloproteinases and gastrointestinal tract cancers].

PMID- 15864211
TI  - [Late abdominal compartment syndrome secondary to traumatic gallbladder rupture].
AB  - A case of abdominal compartment syndrome following hepatic rupture with
      gallbladder tear is reported. We discuss the physiology, diagnosis criteria and
      treatment of this potentially life-threatening complication.

PMID- 15864212
TI  - Major hepatectomy for peripheral papillary cholangiocarcinoma with hilar
      extension in a patient with situs ambiguous.
AB  - Situs ambiguous is a rare anomaly, which includes various abnormalities of
      position and development of trunk organs and results in diagnostic and
      therapeutic problems during major abdominal intervention. We report the case of a
      woman with peripheral papillary cholangiocarcinoma and hilar extension, developed
      on situs ambiguous associated with the following abnormalities: agenesis of the
      retrohepatic vena cava, preduodenal portal vein, a variant of the hepatic
      arteries, truncated pancreas, polysplenia, and mesenteric malrotation. After
      complete anatomical assessment, resection of segments 4 to 8 extended to the
      common bile duct with lymphadenectomy and reconstruction by hepaticojejunostomy
      was performed with no surgical complications. The patient was alive with no signs
      of recurrence at 18 month follow-up. The specificities of situs ambiguous must be
      identified by anatomical assessment but do not prevent complex abdominal surgery.

PMID- 15864213
TI  - [Oxaliplatin neurotoxicity: a report of three cases with post-operative
      exacerbation].
AB  - Liver metastases of colorectal cancer are rarely rapidly resectable. The efficacy
      of new chemotherapy regimen, in particular the combination of 5FU and oxaliplatin
      make further surgical resection possible in the case of an objective response in
      some patients. Three patients with metastatic colorectal cancer received
      oxaliplatin-based chemotherapy; only minimal and transient neurosensory toxicity
      occurred. After a partial response to treatment, surgical resection of metastases
      was performed. Patients reported major exacerbation of oxaliplatin-induced
      neurosensory toxicity following surgery (between day 7 and day 15). One patient
      experienced sensory loss of the extremities with functional impairment (grade 3
      on Levi's scale). The symptoms persisted for 812 months after surgery in the
      three patients. Only seven similar cases have been reported. Toxicity could be
      associated with the concentration of oxaliplatin in the red blood cells:
      oxaliplatin binds irreversibly to erythrocytes. This exacerbation could be the
      consequence of peroperative hemolysis with a redistribution of the pool of intra
      erythrocytic oxaliplatin biotransformation products into the plasma. We did not
      find any relationship with anesthesic or per-operative medications. Studies are
      necessary to define the precise mechanism and the frequency of this reaction.

PMID- 15864214
TI  - From pancreatic intraepithelial neoplasia to cancer: a dramatic progression with
      K-ras status analysis.
AB  - Pancreatic ductal carcinomas are thought to arise from precursor ductal lesions
      called pancreatic intra-epithelial neoplasias or PanINs. We report the case of a
      woman suffering from idiopathic chronic pancreatitis associated with PanINs
      lesions who developed six years later an invasive ductal carcinoma.
      Immunohistochemistry for p53, HER-2/neu and genetic analysis of K-ras oncogene
      were performed at different stages of disease and revealed that the PanINs and
      the carcinoma did not express p53 and HER-2/neu gene products whereas a K-ras
      mutation was present at the carcinoma stage. The relationship between cancer and
      chronic pancreatitis and the main difficulties concerning the early diagnostic of
      pancreatic cancer are discussed.

PMID- 15864215
TI  - [Mediastinal lymph node and vertebral metastases 3 years after liver
      transplantation for cholangiocarcinoma: 2 unusual localizations].

PMID- 15864216
TI  - [Innate immunity, Toll like receptors and cirrhosis].

PMID- 15864217
TI  - Very early cardiac magnetic resonance imaging for quantification of myocardial
      tissue perfusion in patients receiving tirofiban before percutaneous coronary
      intervention for ST-elevation myocardial infarction.
AB  - BACKGROUND: Assessment of myocardial blood flow is important for identification
      and monitoring of microvascular effects of glycoprotein IIb/IIIa inhibitors.
      Magnetic resonance imaging is a novel noninvasive method providing complementary
      information on myocardial blood flow and cardiac function. METHODS AND RESULTS:
      Patients (n = 53) admitted within 12 (mean, 5.8) hours after onset of symptoms
      were randomized to tirofiban or standard therapy before primary percutaneous
      coronary intervention (PCI) with stenting. Myocardial blood flow was graded by
      measurement of corrected Thrombolysis in Myocardial Infarction frame counts and
      by semiquantitative analysis of signal intensity curves from first-pass contrast
      enhanced magnetic resonance perfusion. Pretreatment with tirofiban proved safe
      and resulted in a significantly lower corrected Thrombolysis in Myocardial
      Infarction frame counts (21 vs 34, P = .008) indicating improved myocardial blood
      flow. Magnetic resonance imaging revealed higher normalized peak signal
      intensities (2.19 vs 1.63, P = .046) and a trend to steeper upslopes (0.79 vs
      0.48, P = .1). Cardiac left ventricular wall motion analysis resulted in a
      significantly lower number of myocardial segments with abnormal wall thickening
      (6.4 vs 8.5, P = .025). CONCLUSIONS: Pretreatment with tirofiban appears safe and
      improves myocardial flow after primary PCI with stenting. Magnetic resonance
      imaging proved useful as a complementary method for noninvasive assessment of
      myocardial blood flow and cardiac function in patients with ST-segment elevation
      myocardial infarction undergoing primary PCI.

PMID- 15864218
TI  - Lipid-independent effects of statins on endothelial function and bioavailability
      of nitric oxide in hypercholesterolemic patients.
AB  - BACKGROUND: Experimental evidence suggests a lipid-independent effect of statins
      on endothelial function and nitric oxide (NO) availability in humans. We
      investigated whether improvement in NO availability in hypercholesterolemia can
      be achieved rapidly with statins before lipid-lowering therapy is complete.
      METHODS: We studied 41 patients (52 +/- 11 years) with low-density lipoprotein
      (LDL) cholesterol > or = 130 mg/dL (179 +/- 45 mg/dL) randomly assigned to
      treatment either with atorvastatin (20 mg/day) or cerivastatin (0.4 mg/day).
      Endothelium-dependent vasodilation of the forearm vasculature was measured by
      plethysmography and intra-arterial infusion of acetylcholine (ACh) after 3 days
      (n = 18) and 14 days (n = 39) of treatment. NO availability and oxidative stress
      were assessed by coinfusion of l-NMMA and vitamin C. RESULTS: After 3 days of
      treatment, LDL-cholesterol decreased by 11.9% with a further decrease to 29.6%
      after 14 days ( P < .001). Endothelium-dependent vasodilation improved by +46.7%
      after 3 days of statin therapy compared with before therapy (ACh 48 microg/min:
      +15.7 +/- 10.6 vs +10.7 +/- 10.8 mL/min per 100 mL, P < .05). No further
      improvement in endothelium-dependent vasodilation (+42.7% compared with before
      therapy) could be demonstrated after 14 days of treatment (ACh 48 microg/min:
      +17.7 +/- 10.3 vs +12.4 +/- 9.3 mL/min per 100 mL before therapy, P < .001).
      Coinfusion of ACh plus vitamin C was able to improve endothelium-dependent
      vasodilation before but not after 3 or 14 days of statin therapy either. The
      improvement in endothelium-dependent vasodilation after therapy was no longer
      observed when the NO-synthase inhibitor l-NMMA was coinfused together with ACh.
      CONCLUSIONS: Short-term lipid-lowering therapy with statins is able to improve
      endothelial function and NO availability almost completely after 3 days in
      hypercholesterolemic patients probably by decreasing oxidative stress. This
      improvement seems to be more rapid than the accompanying decline in LDL
      cholesterol and not related to these lipid changes. This finding can support the
      concept of lipid-independent effects of statins in humans.

PMID- 15864219
TI  - Primary stenting of occluded native coronary arteries II--rationale and design of
      the PRISON II study: a randomized comparison of bare metal stent implantation
      with sirolimus-eluting stent implantation for the treatment of chronic total
      coronary occlusions.
AB  - Primary intracoronary stent placement after successfully crossing chronic total
      occlusions (CTO) decreases the high restenosis rate at long-term follow-up
      compared with conventional balloon angioplasty. Several studies have shown the
      efficacy of sirolimus-eluting stents in selected groups of patients. Whether
      sirolimus-eluting stents are superior to bare metal stents in CTO is unknown. In
      this prospective randomized trial, bare metal stent implantation will be compared
      with sirolimus-eluting stent implantation for the treatment of CTO. A total of
      200 patients will be followed up for 12 months with angiographic follow-up at 6
      months. Quantitative coronary analysis will be performed by an independent core
      laboratory. The primary end point is the binary angiographic restenosis and
      reocclusion rate.

PMID- 15864220
TI  - Is atorvastatin more appropriate to use in combination with niacin than
      simvastatin in patients with the metabolic syndrome?

PMID- 15864221
TI  - Angiotensin-converting enzyme inhibitors as a new therapy for atrial
      fibrillation? Controversy.

PMID- 15864222
TI  - Evaluation of a pharmacokinetic program for adjusting enoxaparin in renal
      impairment.

PMID- 15864223
TI  - Statins in acute coronary syndromes: the sooner, the better?

PMID- 15864224
TI  - Statin therapy--time to turn the focus from efficacy to implementation?

PMID- 15864225
TI  - Plaque regression--a new target for antiatherosclerotic therapy.

PMID- 15864226
TI  - New-onset paroxysmal atrial fibrillation: is permanence inevitable?

PMID- 15864227
TI  - Prevalence of anemia and effects on mortality in patients with heart failure.
AB  - BACKGROUND: In patients with chronic kidney disease, the adverse cardiovascular
      effects of anemia have been well established. New data are emerging to suggest
      anemia may represent an important treatable cause of cardiac morbidity and
      mortality in patients with heart failure. To improve the understanding of the
      problem of anemia in heart failure, it is important to assess the factors that
      influence the prevalence of anemia and to assess the consistency of the
      association of anemia and mortality in various populations of patients with heart
      failure. METHODS: A systematic review of the literature was conducted by
      performing detailed searches of MEDLINE and EMBASE, searching the bibliographies
      of the articles retrieved during the database search, and conferring with heart
      failure experts involved in clinical trials. Twenty-eight publications from 26
      studies that evaluated anemia prevalence with or without effects on mortality in
      patients with heart failure were identified. The definition of anemia used in
      each study was tabulated along with pertinent patient characteristics, the
      prevalence of anemia, and the association between anemia and mortality. RESULTS:
      Anemia is common among patients with heart failure. The prevalence of anemia
      increases with increasing severity of heart failure, declining renal function,
      and increasing age. Anemia is consistently associated with poorer survival in all
      patient populations, but there are substantial differences in the patient
      populations and definition of anemia. CONCLUSIONS: To clarify the prognostic
      relationship of anemia in patients with heart failure, a standard definition of
      anemia should be adopted accounting for the menopausal status of women. Age,
      severity of heart failure, evaluation of kidney function, important
      comorbidities, and use of angiotensin-converting-enzyme inhibitors should be
      included, and correctable causes of anemia should be excluded. Inclusion of these
      factors should allow better definition of the relationship between anemia and
      prognosis in patients with heart failure.

PMID- 15864228
TI  - Assessment of Pexelizumab in Acute Myocardial Infarction (APEX AMI): a
      multicenter, randomized, double-blind, parallel-group, placebo-controlled study
      of pexelizumab in patients with acute myocardial infarction undergoing primary
      percutaneous coronary intervention.

PMID- 15864229
TI  - Rationale--Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT):
      evolving the management of cardiovascular risk in patients with chronic kidney
      disease.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) have a high burden of
      mortality and cardiovascular morbidity. Additional strategies to modulate
      cardiovascular risk in this population are needed. Data suggest that anemia is a
      potent and potentially modifiable risk factor for cardiovascular disease in
      patients with CKD, but these data remain unsubstantiated by any randomized
      controlled trial (RCT). Furthermore, the clinical practice guidelines for anemia
      management in patients with CKD are based on limited data. The need for new RCTs
      to address critical knowledge deficits, particularly with regard to the impact of
      anemia therapy on cardiovascular disease and survival, is recognized within the
      guidelines and independent comprehensive reviews of the existing published trial
      data. STUDY DESIGN: The Trial to Reduce Cardiovascular Events with Aranesp (Amgen
      Inc, Thousand Oaks, Calif) (darbepoetin alfa) Therapy (TREAT) is a 4000-patient,
      multicenter, double-blind RCT, designed to determine the impact of anemia therapy
      with darbepoetin alfa on mortality and nonfatal cardiovascular events in patients
      with CKD and type 2 diabetes mellitus. Subjects will be randomized in a 1:1
      manner to either darbepoetin alfa therapy to a target hemoglobin (Hb) of 13 g/dL
      or control, consisting of placebo for Hb > or =9 g/dL or darbepoetin alfa for Hb
      <9 g/dL until Hb is again Hb > or =9 g/dL. TREAT is event-driven and has a
      composite primary end point comprising time to mortality and nonfatal
      cardiovascular events, including myocardial infarction, myocardial ischemia,
      stroke, and heart failure. TREAT will provide data that are critical to evolution
      of the management of cardiovascular risk in this high-risk population.

PMID- 15864230
TI  - Coronary drug-eluting stent development: issues in trial design.

PMID- 15864231
TI  - Conducting economic evaluations alongside multinational clinical trials: toward a
      research consensus.
AB  - Demand for economic evaluations in multinational clinical trials is increasing,
      but there is little consensus about how such studies should be conducted and
      reported. At a workshop in Durham, North Carolina, we sought to identify areas of
      agreement about how the primary findings of economic evaluations in multinational
      clinical trials should be generated and presented. In this paper, we propose a
      framework for classifying multinational economic evaluations according to (a) the
      sources of an analyst's estimates of resource use and clinical effectiveness and
      (b) the analyst's method of estimating costs. We review existing studies in the
      cardiology literature in the context of the proposed framework. We then describe
      important methodological and practical considerations in conducting multinational
      economic evaluations and summarize the advantages and disadvantages of each
      approach. Finally, we describe opportunities for future research. Delineation of
      the various approaches to multinational economic evaluation may assist
      researchers, peer reviewers, journal editors, and decision makers in evaluating
      the strengths and limitations of particular studies.

PMID- 15864232
TI  - Early initiation of lipid-lowering therapy for acute coronary syndromes improves
      compliance with guideline recommendations: observations from the Orbofiban in
      Patients with Unstable Coronary Syndromes (OPUS-TIMI 16) trial.
AB  - BACKGROUND: Lipid-lowering is effective in the prevention of cardiovascular
      morbidity and mortality in patients with coronary artery disease, but effective
      strategies for improving the implementation of these therapies are needed.
      METHODS: In the 10,288 patients in the OPUS-TIMI 16 trial, patients were
      stratified by use of lipid-lowering therapy during index hospitalization and were
      compared for use of lipid-lowering therapy at follow-up as well as for clinical
      outcomes. RESULTS: Lipid-lowering therapy was used in 38% of patients during the
      index hospitalization, of which 94% were statins. At 10 months, 88% of patients
      who were discharged on lipid-lowering medications remained on these drugs.
      Conversely, only 34% of patients not discharged on lipid-lowering medications
      were receiving them at 10 months. Forty-one percent of patients with prior
      history of hyperlipidemia requiring treatment were not discharged on lipid
      lowering therapy, and of these, only 51% were subsequently started on a lipid
      lowering medication as an outpatient despite clear indications. Patients treated
      as inpatients with lipid-lowering therapy had a lower mortality rate at 10 months
      adjusted by propensity analysis (3.1% vs 5.1%, P < .0001) than patients not
      treated with lipid-lowering therapy. CONCLUSION: In patients with acute coronary
      syndromes, the initiation of lipid-lowering therapy in the inpatient setting
      increases the rate of its subsequent use at 10 months, making this an important
      method of ensuring appropriate secondary prevention.

PMID- 15864233
TI  - Atorvastatin has an important acute anti-inflammatory effect in patients with
      acute coronary syndrome: results of a randomized, double-blind, placebo
      controlled study.
AB  - BACKGROUND: C-reactive protein (CRP) levels are associated with cardiovascular
      risk. We assessed the hypothesis that atorvastatin might have anti-inflammatory
      effects in acute coronary syndromes (ACS) as shown by CRP reduction. METHODS:
      This study was a prospective, randomized, double-blind, placebo-controlled study
      of 90 consecutive patients admitted within 48 hours of onset of ACS with CRP
      levels > or =1.4 mg/dL. Patients were assigned to atorvastatin 40 mg daily or
      placebo over 30 days. C-reactive protein levels, lipid profiles, serum
      fibrinogen, white cell count, and erythrocyte sedimentation rate were measured at
      entry, hospital discharge, and 1 month later. RESULTS: Baseline clinical
      characteristics did not differ between atorvastatin and placebo groups (mean age
      59.3 +/- 13.4 vs 61.1 +/- 11.5, P = ns); myocardial infarction 52.3% versus 67.4%
      ( P = ns). In both groups, median baseline CRP levels were comparable (5.97 +/-
      6.2 vs 4.64 +/- 4.2 mg/dL, P = ns). C-reactive protein levels were lower in the
      atorvastatin group versus control group at discharge (1.68 +/- 1.65 vs 4.12 +/-
      4.18 mg/dL) and at 30 days (0.50 +/- 0.71 vs 2.91 +/- 2.68 mg/dL, both P <
      .0001). C-reactive protein levels significantly decreased from baseline to
      discharge and 1 month later in placebo and atorvastatin groups (both P < .0001);
      however, the reduction was greater in the atorvastatin group (62% vs 11% at
      discharge [P < .0001]; 84% vs 30% at 1 month [P < .0001]). In addition,
      atorvastatin was associated with a reduction in total and low-density lipoprotein
      cholesterol and erythrocyte sedimentation rate at discharge and at 30 days (P <
      .0001 for all comparisons). No correlation was found between changes in CRP and
      cholesterol levels. CONCLUSIONS: C-reactive protein levels in ACS were rapidly
      reduced with atorvastatin. These data provide evidence that statins have fast and
      early anti-inflammatory effects in addition to lipid-lowering effects in ACS.

PMID- 15864234
TI  - Electrocardiographic damage scores and cardiovascular mortality.
AB  - BACKGROUND: A number of electrocardiogram (ECG) classification systems have been
      developed to estimate cardiac injury, infarct size, and left ventricular
      function. Although many studies have documented an association between clinical,
      imaging, and autopsy data, few have evaluated their prognostic value. METHODS AND
      RESULTS: ECGs from 46,933 patients were analyzed using computerized measurements
      and algorithms. The Simplified Selvester Score, the Cardiac Infarction Injury
      Score (CIIS), and a Q-wave score were calculated. Other ECG characteristics such
      as left ventricular hypertrophy and bundle-branch blocks were also evaluated. The
      main outcome was cardiovascular (CV) mortality. During a mean follow-up of 6
      years, the CIIS outperformed all other ECG classifications in determining
      prognosis. Going from lowest to highest tertile of CIIS, each step had a hazard
      ratio of 1.39 (CI 1.32-1.45) or a 39% increase in risk per tertile. Using
      clinically based thresholds, the annual mortality for high-risk CIIS was 4.5% (CI
      4.0-4.6) versus 0.3% (CI 0.0-1.3) for those in the low-risk group. CONCLUSIONS: A
      low-risk damage score was associated with a <1% annual CV mortality and a high
      risk damage score with annual CV mortality of >4%. A damage score should be
      calculated as part of all computerized ECG interpretations.

PMID- 15864235
TI  - Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin)
      versus atorvastatin in patients with hypercholesterolemia: the Vytorin Versus
      Atorvastatin (VYVA) study.
AB  - BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) is the primary
      therapeutic target in the National Cholesterol Education Program Adult Treatment
      Panel III (ATP III) guidelines. This study tested the hypothesis that
      ezetimibe/simvastatin, a lipid-lowering agent that inhibits both intestinal
      cholesterol absorption and cholesterol synthesis, provides greater LDL-C
      reductions than atorvastatin across dose ranges. METHODS: This multicenter,
      double-blind, 6-week parallel-group study randomized 1902 patients with LDL-C
      above ATP III goal to atorvastatin (10, 20, 40, or 80 mg) or to
      ezetimibe/simvastatin (10/10, 10/20, 10/40, or 10/80 mg). Patients were
      stratified by prerandomization LDL-C level. RESULTS: At each milligram-equivalent
      statin dose comparison, and averaged across doses, ezetimibe/simvastatin provided
      greater LDL-C reductions (47%-59%) than atorvastatin (36%-53%).
      Ezetimibe/simvastatin 10/40 and 10/80 mg also provided significantly greater high
      density lipoprotein cholesterol (HDL-C) increases than atorvastatin 40 and 80 mg.
      Triglyceride reductions were similar for all comparisons. More
      ezetimibe/simvastatin than atorvastatin patients with coronary heart disease
      (CHD) or CHD risk equivalents attained the ATP III LDL-C goal of <100 mg/dL and
      the optional LDL-C target of <70 mg/dL. C-reactive protein reductions were
      similar between treatment groups. Consecutive elevations in alanine
      aminotransferase and/or aspartate aminotransferase occurred in significantly more
      atorvastatin patients than ezetimibe/simvastatin patients. No myopathy or liver
      related adverse events led to study discontinuation with either drug.
      CONCLUSIONS: Ezetimibe/simvastatin was more effective than atorvastatin in
      lowering LDL-C at each dose comparison and provided greater increases in HDL-C at
      the 40- and 80-mg statin dose. Ezetimibe/simvastatin is a highly efficacious,
      well-tolerated treatment option for hypercholesterolemic patients.

PMID- 15864236
TI  - Influence of clinical trial enrollment on the quality of care and outcomes for
      patients with non-ST-segment elevation acute coronary syndromes.
AB  - BACKGROUND: Clinical trials provide evidence that is formulated into
      recommendations for practice guidelines, but it remains uncertain whether
      patients enrolled in trials are similar to those treated in routine practice and
      whether trial enrollment influences inhospital treatments and outcomes. METHODS:
      Using data from the CRUSADE quality improvement initiative, we evaluated
      predictors of trial enrollment, treatment patterns, and clinical outcomes among
      high-risk patients with non-ST-segment elevation acute coronary syndromes (NSTE
      ACS) who were and were not enrolled in a clinical trial during hospitalization.
      RESULTS: Among 55,172 high-risk patients presenting with NSTE ACS at 443 US
      hospitals, 1397 (2.5%) patients were enrolled in a clinical trial during index
      hospitalization. Significant predictors of trial enrollment included male sex,
      lack of renal insufficiency, and absence of congestive heart failure on
      presentation. Acute (<24 hours) and discharge secondary prevention interventions
      recommended by the American College of Cardiology/American Heart Association
      guidelines for NSTE ACS were used more commonly in patients enrolled in clinical
      trials. Cardiac catheterization (84.5% vs 65.8%, P < .0001), percutaneous
      coronary intervention (48.2% vs 36.3%, P < .0001), and bypass surgery (19.1% vs
      11.3%, P < .0001) were also performed more frequently in trial patients. The
      adjusted risk of inhospital mortality was similar in trial versus nontrial
      patients (odds ratio 0.86, 95% CI 0.60-1.24). CONCLUSIONS: Patients with NSTE ACS
      participating in clinical trials are more likely to receive beneficial therapies
      and interventions throughout hospitalization, but preferential recruitment of
      patients with lower-risk features may limit the external validity of trial
      results.

PMID- 15864237
TI  - Reducing the costs of phase III cardiovascular clinical trials.
AB  - BACKGROUND: The pharmaceutical industry spends approximately 26.4 billion dollars
      annually for research and development (4.1 billion dollars in cardiovascular
      products). We compared pharmaceutical companies' planned resource use and costs
      in Phase III cardiovascular trials and identified cost-saving strategies. METHODS
      AND RESULTS: We developed 2 case scenarios (a 17,000-patient, open-label acute
      coronary syndromes [ACS] trial and a 14,500-patient, double-blind congestive
      heart failure [CHF]) trial and surveyed 6 pharmaceutical experts about expected
      resources (e.g., number of sites, case report form [CRF] pages, and monitoring
      visits) needed for the trials. Using a validated model, we estimated costs under
      each expert's assumptions. ACS trial costs averaged 83 million dollars (median,
      67 million dollars; range, 57 dollars to 158 million dollars) and 142 million
      dollars (median, 135 million dollars; range, 102 dollars to 207 million dollars)
      for the CHF trial. Site-related expenses (site management and payments) were >65%
      of total costs for both trials. In sensitivity analyses, total costs were reduced
      >40% by simultaneously reducing CRF pages, monitoring visits, and site-payment
      amounts but maintaining the numbers of patients and sites. CONCLUSIONS: With a
      set number of sites and patients, the most efficient way to reduce trial costs
      and still meet the trial's scientific objectives is to reduce management
      complexity. Modest changes in management parameters release significant monies to
      answer more research questions.

PMID- 15864238
TI  - Progression to chronic atrial fibrillation after the initial diagnosis of
      paroxysmal atrial fibrillation: results from the Canadian Registry of Atrial
      Fibrillation.
AB  - BACKGROUND: After its initial diagnosis, atrial fibrillation (AF) may progress
      from paroxysmal to chronic AF (CAF). The rate of progression and risk factors for
      progression are not clearly defined. METHODS: The Canadian Registry of Atrial
      Fibrillation (CARAF) enrolled patients from 6 Canadian cities at the time of
      their first electrocardiographic diagnosis of AF. Comprehensive clinical and
      echocardiographic data were collected and patients were followed annually,
      carefully documenting clinical outcomes, recurrence of paroxysmal AF, and
      progression to CAF. Baseline clinical, electrocardiographic, and
      echocardiographic variables were evaluated by univariate Cox proportionate
      hazards analysis. A stepwise approach was used to model the association between
      echocardiographic and clinical variables with progression to CAF. RESULTS: A
      total of 757 patients with a baseline diagnosis of paroxysmal AF were evaluated.
      Median follow-up was 8.0 years (range 2 days to 11.1 years). The probability of
      progression to CAF by 1 year was 8.6% and thereafter there was a slow but steady
      progression to 24.7% by 5 years. By 5 years, the probability of documented
      recurrence of any AF (chronic or paroxysmal) was 63.2%. Increasing age,
      significant aortic stenosis or mitral regurgitation, left atrial enlargement, and
      diagnosis of cardiomyopathy were independently associated with progression to
      CAF. A more rapid heart rate during AF was associated with decreased risk of
      progression. CONCLUSIONS: After the initial diagnosis of paroxysmal AF, there is
      a slow but steady progression to CAF. Baseline echocardiographic variables, age,
      cardiomyopathy, and heart rate were independently associated with progression to
      CAF.

PMID- 15864239
TI  - Left ventricular systolic asynchrony after acute myocardial infarction in
      patients with narrow QRS complexes.
AB  - BACKGROUND: The aim of the study was to assess the degree of left ventricular
      (LV) asynchrony after myocardial infarction (MI) in patients with a narrow QRS
      complex using tissue Doppler imaging (TDI) and correlate this with the site and
      extent of the infarction measured by contrast-enhanced magnetic resonance imaging
      (Ce-MRI). METHODS: Echocardiography with TDI and Ce-MRI was performed within 6
      days of acute MI in 47 patients and compared with 69 age-matched healthy
      volunteers. Regional myocardial velocities were assessed in 12 segments, and the
      corresponding systolic velocity (Sm), early diastolic velocity (Em), as well as
      the time to peak Sm (Ts) and time to peak Em (Te) were measured. To assess LV
      synchronicity, SDs of Ts (Ts-SD) and Te (Te-SD) of all 12 segments were computed.
      Location and size of infarct were confirmed by Ce-MRI with a 16-segment model.
      RESULTS: All the patients had a normal QRS complex duration. The Ts-SD was
      significantly prolonged in the MI group when compared with controls (42.2 +/-
      13.7 vs 18.0 +/- 7.0 milliseconds, P < .001). The Ts-SD was longer in patients
      with anterior than inferior MI (46.8 +/- 13.9 vs 34.6 +/- 8.5 milliseconds, P =
      .002). Stepwise multiple regression analysis revealed that infarct size was the
      main independent predictor of systolic asynchrony ( B = 0.79, 95% CI 0.75-1.23, P
      < .001). Asynchrony was not related to the transmurality of the infarction.
      CONCLUSIONS: Myocardial infarction has a significant impact on LV synchronicity
      even in those with a narrow QRS complex. The degree of LV systolic asynchrony is
      mainly determined by the infarct size and not transmurality.

PMID- 15864240
TI  - Long-term benefits of an early invasive management in acute coronary syndromes
      depend on intracoronary stenting and aggressive antiplatelet treatment: a
      metaregression.
AB  - BACKGROUND: Although recent data support an early invasive management in acute
      coronary syndromes (ACS), overall evidence appears conflicting. We performed a
      metaregression to explore the impact of intracoronary stenting and aggressive
      antiplatelet treatment on the risk/benefit ratio of an early invasive approach.
      METHODS: We searched several databases up to March 2004 for randomized trials
      comparing an early invasive versus delayed invasive or conservative management in
      ACS. Random-effects odds ratios were computed for death and/or myocardial
      infarction at the longest follow-up. Log (odds ratios) were tested for
      interaction with stenting and aggressive antiplatelet treatment (ie, glycoprotein
      IIb/IIIa inhibitors or thienopyridines in addition to aspirin). RESULTS: Ten
      trials (9990 patients, median follow-up 12 months) were pooled. Overall, an early
      invasive management was associated with significantly reduced rates of death or
      myocardial infarction (P = .01). Metaregression analysis showed that the 2 most
      significant predictors of the benefits of an early invasive strategy in patients
      with ACS on event-free survival were the use, in subjects managed invasively, of
      aggressive antiplatelet treatment (P = .005) and stenting (P = .011). Moreover,
      both stenting and aggressive antiplatelet treatment were significantly associated
      with reduced mortality (respectively, P = .014 and P = .009) and correlated to
      each other (r = 0.76, P = .010). CONCLUSIONS: This study shows that the benefits
      of an early invasive approach in patients with ACS are significantly associated
      with concomitant aggressive antiplatelet treatment and stenting. These findings
      thus suggest the overall superiority of an early invasive approach in ACS, as
      long as state-of-the-art therapies are implemented.

PMID- 15864241
TI  - Association of chronic kidney disease with clinical outcomes after coronary
      revascularization: the Arterial Revascularization Therapies Study (ARTS).
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with adverse outcomes
      after coronary artery bypass graft surgery (CABG) and percutaneous coronary
      interventions (PCI), but it is unclear which of these revascularization
      strategies is associated with lower risk for morbidity and mortality in this
      population. In the Arterial Revascularization Therapies Study (ARTS), we compared
      long-term clinical outcomes after CABG or PCI with multivessel stenting in
      patients with CKD. METHODS: The ARTS randomly assigned 1205 participants with and
      without CKD to CABG or PCI with multivessel stenting. We defined CKD as
      creatinine clearance < or =60 mL/min, estimated by the Cockroft-Gault equation.
      The primary outcome was the composite of death, myocardial infarction (MI), or
      stroke; and, a secondary outcome was repeat revascularization. Participants were
      followed for a mean of 3 years after their intervention. We evaluated whether
      randomization to CABG or PCI was associated with different outcomes among
      participants with CKD. RESULTS: Two hundred ninety participants (25%) had CKD at
      entry into ARTS. One hundred fifty-one received PCI, and 139 received CABG. No
      difference was observed in the primary endpoint with CABG or PCI among CKD
      participants (adjusted Hazard Ratio [HR] CABG vs PCI = 0.93; 95% CI 0.54-1.60; P
      = .97). However, CABG was associated with a reduced risk for repeat
      revascularization (HR = 0.28; 95% CI 0.14-0.54; P < .01). Compared with
      participants with normal renal function, CKD was associated with a nearly 2-fold
      risk for the primary outcome (unadjusted HR = 1.9; 95% CI 1.4-2.7; P < .01).
      After multivariate adjustment, this association remained significant (HR 1.6; 95%
      CI 1.1-2.4). CONCLUSIONS: In patients with multivessel CAD and CKD, treatment
      with CABG or PCI with multivessel stenting led to similar outcomes of death, MI,
      or stroke, but CABG was associated with decreased repeat revascularizations. When
      compared with ARTS participants with normal renal function, those with CKD had
      substantially elevated risk of adverse clinical outcomes after coronary
      revascularization.

PMID- 15864242
TI  - Simvastatin does not inhibit intimal hyperplasia and restenosis but promotes
      plaque regression in normocholesterolemic patients undergoing coronary stenting:
      a randomized study with intravascular ultrasound.
AB  - BACKGROUND: Restenosis after coronary stenting is mainly caused by intimal
      hyperplasia. Both experimental and clinical studies suggest that statins may be
      able to inhibit intimal hyperplasia and, therefore, in-stent restenosis (ISR), by
      mechanisms beyond lipid lowering. METHODS: In a 12-month study, we randomized 71
      normocholesterolemic patients to 20 mg simvastatin or no treatment, 2 weeks
      before elective coronary stenting. Patients were evaluated by quantitative
      coronary angiography and intravascular ultrasound, immediately after the index
      procedure and at the 12-month catheterization. RESULTS: Binary ISR was present in
      15% and in 18% of simvastatin-treated patients and controls, respectively (P =
      NS). Intimal hyperplasia did not differ significantly between the 2 groups (3.6
      +/- 1.8 vs 3.8 +/- 2.3 mm3/mm, 34% +/- 15% vs 35% +/- 23% for simvastatin vs
      controls, P = NS). However, persistent plaque decreased with simvastatin but
      increased in controls (-4.0 +/- 4.0 vs +1.6 +/- 3.8 mm3/mm, -14% +/- 10% vs +6%
      +/- 12%, P < .05). The same behavior was shown by intermediate plaques at
      nonstented sites (-2.5 +/- 3.0 vs +1.0 +/- 3.0 mm3/mm, -10% +/- 8% vs +9% +/- 9%,
      P < .05). Major adverse events at 12 months were present in 11% and 24% of
      simvastatin-treated patients and controls, respectively (P = .20). CONCLUSIONS:
      In normocholesterolemic patients undergoing coronary stenting, simvastatin does
      not prevent intimal hyperplasia or ISR, but it promotes atherosclerotic
      regression both at stented and at nonstented sites.

PMID- 15864243
TI  - Exercise treadmill testing using a modified exercise protocol in women with
      suspected myocardial ischemia: findings from the National Heart, Lung and Blood
      Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).
AB  - BACKGROUND: Exercise testing, a major diagnostic modality in individuals with
      suspected coronary artery disease (CAD), has in general demonstrated less overall
      diagnostic accuracy in women compared to men. As part of the WISE, a modified
      protocol was examined with the intention of improving reliability of exercise
      testing. METHODS: Criteria for entry in the WISE study include clinically
      indicated coronary angiography. Exercise testing was performed using a protocol
      modified to be more appropriate for women. The study population consisted of 96
      women, mean age of 55.8 y (range 34-77), who completed exercise treadmill test
      (ETT). Most (78%) were postmenopausal; 96% had >or =2 risk factors for CAD.
      RESULTS: By core laboratory angiography, 29/96 women had stenosis > or =50% in at
      least one coronary artery. Of these 29 women, 9 had abnormal ETT, yielding
      overall sensitivity of 31%. The remaining 20 women had normal (12/29, 41%) or
      nondiagnostic (8/29, 28%) studies. Among the 67 women with minimal or no coronary
      stenosis, 35 had no ischemic ST-segment changes during ETT, yielding overall
      specificity of 52%. Analysis with exclusion of women with nondiagnostic studies
      yielded sensitivity and specificity of 43% and 66%, respectively. The presence of
      coronary artery stenosis and inability to perform ETT, but not results of
      testing, predicted the outcomes of myocardial infarction, heart failure, and
      death. CONCLUSIONS: Exercise treadmill test appears to be of limited diagnostic
      value in women with suspected myocardial ischemia referred for coronary
      angiography. Sensitivity and specificity remain poor even with modified exercise
      protocol and core laboratory angiographic analysis. These findings merit
      consideration in view of current guidelines that recommend exercise testing in
      women with suspected CAD.

PMID- 15864244
TI  - Prediction of death or myocardial infarction by exercise single photon emission
      computed tomography perfusion scintigraphy in patients who have had recent
      coronary artery stenting.
AB  - BACKGROUND: Although practice guidelines do not recommend routine exercise
      testing of patients after coronary stenting, several small studies have suggested
      that stress myocardial perfusion imaging can provide prognostic information about
      future adverse cardiac events. We sought to determine if exercise nuclear testing
      provides independent prognostic information in patients after coronary stenting.
      METHODS: We analyzed the outcomes of 370 patients who underwent dual isotope
      exercise nuclear scintigraphy at least 1 month after coronary stenting and had
      testing between April 1996 and May 2002. Patients were classified according to
      presence or absence of any ischemia. The primary endpoint was all-cause mortality
      or myocardial infarction (MI) during a median of 30 months (range 6-59) of follow
      up. RESULTS: There were 86 patients (23%) who had ischemia. Major events--death
      or MI--occurred in 62 patients including 22 deaths. Among patients with no
      ischemia, the 30-month event rate was 9.1%, whereas among patients with ischemia,
      the event rate was 17.0% (P = .001). After adjusting for age, sex, standard
      cardiac risk factors, cardiac history, left ventricular ejection fraction,
      angiographic findings, procedural variables, exercise capacity, and heart-rate
      dynamics, the presence of scintigraphic evidence of ischemia predicted death or
      MI (adjusted hazard ratio 2.08, 95% CI 1.21-3.56, P = .008). The presence of
      ischemia similarly predicted events in asymptomatic patients (adjusted hazard
      ratio 2.19, 95% CI 1.17-4.11, P = .015). CONCLUSIONS: In patients with recent
      coronary stent placement, reversible nuclear perfusion defects independently
      predicted risk of death or MI.

PMID- 15864245
TI  - Carvedilol therapy is associated with a sustained decline in brain natriuretic
      peptide levels in patients with congestive heart failure.
AB  - BACKGROUND: Beta-blocker therapy improves symptoms, left ventricular ejection
      fraction (LVEF), and survival in patients with congestive heart failure, but
      chronic effects on neurohormones have not been extensively investigated.
      Therefore, we examined the neurohumoral effects of carvedilol. METHODS: Fifty
      five patients with New York Heart Association (NYHA) classes II-III congestive
      heart failure and LVEF < or =35% entered the study with intention to assess LVEF,
      NYHA class, plasma brain natriuretic peptide (BNP), N-terminal atrial natriuretic
      peptide (NANP), big-endothelin, endothelin-1, norepinephrine, and angiotensin II
      at baseline and at 6 and 12 months after initiation of carvedilol. RESULTS: Forty
      six patients completed 12 months of follow-up. Left ventricular ejection fraction
      improved from 26% +/- 8% at baseline to 39% +/- 14% at 12 months. New York Heart
      Association class improved from 2.3 +/- 0.4 at baseline to 1.8 +/- 0.7 at 12
      months. Brain natriuretic peptide fell from 453 +/- 784 to 208 +/- 393 pg/mL at 6
      months and 223 +/- 334 pg/mL at 12 months ( P = .01 vs baseline). N-terminal
      atrial natriuretic peptide did not change between baseline and 6 months but fell
      at 12 months (2117 +/- 1678, 2015 +/- 1532, and 1438 +/- 1442 pg/mL,
      respectively, P = .001 between baseline and 12 months). Angiotensin II was lower
      at 6 and 12 months than at baseline (12.6 +/- 10, 7.8 +/- 5.5 pg/mL, P < 0.001,
      and 11.3 +/- 17.1 pg/mL, P = .02, respectively). Left ventricular ejection
      fraction at 12 months correlated inversely with BNP level at 12 months (r = 
      0.55, P = .001). CONCLUSIONS: Carvedilol therapy is associated with a sustained
      decline in BNP and NANP levels. Serial BNP levels can provide some guidance
      regarding probability of LVEF improvement, but the relationship is not strong
      enough for BNP levels to supplant measurement of LVEF.

PMID- 15864246
TI  - Valsartan reduces the incidence of atrial fibrillation in patients with heart
      failure: results from the Valsartan Heart Failure Trial (Val-HeFT).
AB  - BACKGROUND: Atrial fibrillation (AF) in heart failure (HF) is generally
      considered a negative prognostic factor. Recent studies indicate that the
      incidence of AF might be decreased by renin angiotensin aldosterone system
      inhibitors. The identification of a treatment to prevent its occurrence is likely
      to improve patients outcome. The aims of these subanalyses of Val-HeFT were to
      assess (a) the effects of valsartan in the prevention of AF, (b) the independent
      predictors of this event, and (c) the prognostic role of AF occurrence. METHODS
      AND RESULTS: The occurrence of AF was evaluated based on adverse event reports in
      the patients with HF enrolled in Val-HeFT. Patients were randomized to valsartan
      or placebo on top of their prescribed treatments for HF. During the mean 23
      months of follow-up, AF was reported in 287/4395 patients (6.53%) in sinus rhythm
      at baseline, of whom 113/2205 (5.12%) were allocated to valsartan and 174/2190
      (7.95%) to placebo (P = .0002). Multivariable analysis showed that brain
      natriuretic peptide (BNP) levels at baseline above the median value (HR 2.28, 95%
      CI 1.75-2.98), age over 70 years (HR 1.51, 95% CI 1.17-1.95), male sex (HR 1.53,
      95% CI 1.07-2.18), and the valsartan treatment (HR 0.63, 95% CI 0.49-0.81) were
      independently associated with AF occurrence. Cox multivariable regression
      analysis showed that occurrence of AF was independently associated with a worse
      prognosis, with the adjusted hazard risks for all-cause mortality and combined
      mortality/morbidity of 1.40 (95% CI 1.16-1.58) and 1.38 (95% CI 1.12-1.70),
      respectively. CONCLUSIONS: The results of the present study demonstrate that (a)
      adding valsartan to prescribed therapy for HF significantly reduces the incidence
      of AF by 37%; (b) BNP level and advanced age were the strongest independent
      predictors for AF occurrence; and (c) AF occurrence further worsens the outcome
      in patients with HF.

PMID- 15864247
TI  - Patients with heart failure who die in hospice.
AB  - BACKGROUND: Patients with end-stage heart failure experience disability, dyspnea,
      pain, and suffering at the end of life despite progress in treatment approaches.
      Little is known about the patients with heart failure in hospice and the impact
      of hospice care on health-related outcomes. METHODS AND RESULTS: The purposes of
      this retrospective, descriptive chart review were to (1) describe the
      characteristics of patients who receive hospice care, (2) identify symptoms most
      commonly reported by patients with heart failure in hospice during the last 7
      days of life, and (3) identify interventions used by hospice nurses to manage the
      symptoms. The majority of the patients were women, widowed, and white. Median
      length of stay was 10 days. Nearly 37% of the patients were admitted to hospice
      during the last week of life. Primary symptoms at admission for hospice care
      included dyspnea, confusion at least some of the time, and poor appetite. There
      was no statistically significant difference in symptoms between the day of
      admission for hospice care and the day of death. Symptom management strategies
      included oxygen, family reassurance or education, skin care, and patient
      education. Medications commonly used to relieve symptoms included antianxiety
      medications, morphine, and/or other narcotics. Although mainstay heart failure
      drugs had been prescribed for some patients, prescription rates were low and not
      in line with current guideline recommendations, nor were those medications
      recorded as being used for symptom management. CONCLUSION: Further research
      including prospective study is needed to clearly articulate the impact of hospice
      care on patients and families affected by heart failure.

PMID- 15864248
TI  - Current topics of tinea capitis in China.
AB  - Tinea capitis is one type of superficial fungal infection which is found all over
      the world. The major etiologic agent of tinea capitis varies in different areas.
      Tinea capitis in China has unique characteristics. The epidemiology, transmission
      and therapy of child and adult tinea capitis in China are reviewed in this paper.

PMID- 15864249
TI  - Phaeohyphomycosis in Korea.
AB  - Phaeohyphomycosis is a mycotic disease caused by dematiaceous fungi that produce
      brown yeast-like cells, pseudohyphae, and irregular true hyphae in tissues. Seven
      Korean cases of subcutaneous phaeohyphomycosis have been reported to date, four
      males and three females, ranging in age from 9-84 years (mean 50.4 years).
      Causative organisms of subcutaneous phaeohyphomycosis were 3 of Exophiala
      jeanselmei, 2 of E. dermatitidis, 1 of Drechslera dematioidea and 1 of Phoma sp.
      Four cases of abscess and 3 cases of verrucous plaque were present as skin
      lesions, and were all exposed areas of the body. Patients were treated with
      itraconazole, ketoconazole, fluconazole or amphotericin B.

PMID- 15864250
TI  - Mycology in the Philippines, revisited.
AB  - The warm tropical climate of the Philippines and its interaction with cultural
      practices, occupation and immune responsiveness contribute to the increased
      susceptibility of Filipinos to fungal infections. An investigation to determine
      the prevalence of fungal infections in dermatology training institutions over a 4
      year period was conducted. The results showed that fungal infections rank as the
      second leading cause of consultation with a prevalence of 12.98%. Pityriasis
      versicolor (25.34%), tinea corporis (22.63%), tinea cruris (16.7%) and tinea
      pedis (16.38%) were the most frequently encountered cases. Fungal culture yield
      is low and Candida sp. is the most common isolate, obtained predominantly from
      specimens taken from the oral mucosa and nails. Candidiasis is still the most
      common opportunistic infection followed by coccidioidomycosis, cryptococcosis and
      aspergillosis. Imidazoles are the most commonly prescribed systemic and topical
      treatment by Filipino dermatologists. Initial data collected would serve as
      reference for future research and may be used to compare with epidemiologic data
      obtained from other Asian countries.

PMID- 15864251
TI  - Superficial fungal infections seen at the National Skin Centre, Singapore.
AB  - Cutaneous fungal infections are common in Singapore. The National Skin Centre is
      a tertiary referral centre for dermatological diseases in the country, and sees
      more than 2,500 cases of superficial fungal infections annually. AIM: This study
      analyses data collated from the centre's medical record office as well as fungal
      culture results from the mycology laboratory. RESULTS: From 1999 to 2003, there
      were a total of 12,903 cases of superficial fungal infections seen at the centre.
      The majority of patients (n=9335) (72.3%) were males. The most common infection
      was tinea pedis (n=3516) (27.3%), followed by pityriasis versicolor (n=3249)
      (25.2%) and tinea cruris (n=1745) (13.5%). Candidal infections were also common
      (n=1430), the majority of which were cases of candidal intertrigo. There were
      very few cases of tinea capitis, which is uncommon in Singapore. The number of
      cases of onychomycosis has shown a rising trend over the past 5 years.
      Trichophyton rubrum was the most prevalent fungal pathogen isolated from all
      cases of superficial fungal infections of the skin, except for tinea pedis, where
      Trichophyton interdigitale was the most frequently isolated organism.
      Dermatophytes remain the most commonly isolated fungal pathogens isolated in
      toenail onychomycosis, whilst Candida species accounted for the majority of
      isolates in fingernail onychomycosis. CONCLUSION: Current epidemiologic trends of
      superficial fungal infections in Singapore show some similarities to recent
      studies from the United Kingdom and United States.

PMID- 15864252
TI  - Mycoses in Thailand: current concerns.
AB  - Scytalidium dimidiatum is the leading cause of fungal foot diseases in Thailand,
      in contrast to similar studies in which dermatophytes have been identified as the
      predominant pathogens. By contrast, the prevalence of Candida albicans in our
      study was only 2.6 approximately 3.0%. Scytalidium fungal foot infection is
      clinically indistinguishable from that caused by dermatophytes and should be
      included as a possible cause of treatment failure in tinea pedis and
      onychomycosis. Without proper culture identification, clinically diagnosed
      patients would be treated with a standard antifungal regimen leading to minimal
      response and be interpreted as drug resistant cases resulting in switching of
      drugs and more aggressive management procedures. Tinea capitis is another health
      problem in young children. However, for Microsporum canis and some ectothrix
      organisms, the effectiveness of treatment may be less than endothrix infection.
      Griseofulvin is still the mainstay antifungal although itraconazole and
      terbinafine are as effective. Pulse regimen may be another option with advantages
      of increased compliance and convenience. Two pulses of terbinafine may be
      sufficient for treating most cases of Microsporum infection, although additional
      treatment may be needed if clinical improvement is not evident at week 8 after
      initiating therapy. Chromoblastomycosis is another subcutaneous infection that
      requires long treatment duration with costly antifungal drugs. The most common
      pathogen in Thailand is Fonsecaea pedrosoi. Preliminary study of pulse
      itraconazole 400 mg/d 1 week monthly for 9-12 consecutive months showed promising
      results. The prevalence of Penicillium marneffei infection is alarming in HIV
      infected patients living in endemic areas. Diagnosis relies on direct examination
      of the specimens and confirmation by culture. Treatment regimens include systemic
      amphotericin B or itraconazole followed by long-term prophylaxis. Treatment
      outcome depends on the immune status of the patient.

PMID- 15864253
TI  - [Epidemiological survey of Trichophyton tonsurans infection in Tohoku district
      and its clinical problems].
AB  - To research the current status of Trichophyton tonsurans infection in Tohoku
      District, I sent out a questionnaire to the main dermatology clinics in the
      Tohoku district. The results showed this infection was found first in spring,
      2001 in Miyagi prefecture, and gradually spread from southern to northern
      districts; the total number of patients is now 162. The number in each prefecture
      is as follows: Yamagata; 88, Miyagi; 68, Akita; 4, Aomori; 2. In Iwate and
      Fukushima, however, no cases were reported. By age distribution high school
      students accounted for 117 (75%), elder patients for 29 (19%), lower age children
      only 10, and 6 cases were uncertain. Judo players accounted for 113 (70%) and
      wrestlers for 39 (24%). Family infections were found in two cases. Latent
      infections were found in several cases, and in one case the infection continued
      for 2.5 years without clinical symptoms. In my clinic 30 cases were observed
      beginning in 2001: high school boys accounted for 11, students of a professional
      school 14, college student 1, adults 3, and those involved in judo 27, wrestling
      2 and mixed grappling sports 2. A family infection between a father and his
      daughter was found. According to the observations in our cases, this fungus
      easily invaded the hair roots from the early stage of infection, but was not
      noticed by common external clinical observations. Thus, microscopic examinations
      are necessary throughout the therapeutic process and to make certain of a
      complete cure. I think also necessary is the systemic administration of
      terbinafine or itraconazole for 4 or 6 weeks or more even for tinea corporis.
      Additionally, I emphasize that culture study is indispensable to confirm the
      infection by this fungi.

PMID- 15864254
TI  - [Questionnaire investigation of incidence of Trichophyton tonsurans infection in
      dermatology clinics in the Kanto area].
AB  - We conducted a questionnaire investigation to learn the incidence of T. tonsurans
      infection. Subjects of this investigation were 1,060 dermatologists in 1,060
      dermatology clinics in the Kanto area to whom questionnaires were mailed. We
      asked each dermatologist whether he/she had experienced T. tonsurans infection
      cases (including suspected cases) and if so, we further asked; a. time of onset,
      b. number of cases, c. sexuality of the patient, d. club that the subject had
      joined (judo club, wrestling club or other), e. age of the subject, and f. number
      of cases suspected of having familial infection, the response rate was 47.5% (504
      of the 1060 doctors), and 25.8% (130 of the 504) had handled T. tonsurans
      infection cases. The total number of patients was 707 (657 males and 50 females),
      with 400 (56.6%) of those in the 18 high-ranking clinics. The number of cases had
      increased rapidly from around 2002; 72.9% of the patients were students in high
      schools and universities and in 8 cases familial infection was suspected. 96.5%
      of the patients were in a judo or wrestling club. Our investigation revealed that
      this infectious disease had spread more than we had expected. It is important to
      develop more reliable infection control measures and to determine the actual
      conditions of this infection using mycological examinations.

PMID- 15864255
TI  - [Survey of Trichophyton tonsurans infection in the Hokuriku and Kinki regions of
      Japan].
AB  - In June 2004, information was gathered on Trichophyton tonsurans infections, both
      past and current, in the Hokuriku and Kinki regions of central-western Honshu
      island, Japan, by questionnaires sent to 185 dermatologists who were members of
      the local medical mycologist associations Hokuriku Shinkin Kondan-kai and Kansai
      Shinkin Kondan-kai. Of the 111 (59.4%) who returned the completed questionnaire,
      32 (28.8%) had seen patients infected with T. tonsurans including suspicious
      cases. The earliest recorded cases were linked to an endemic that occurred in
      1994 or 1995 among a high school wrestling team in Toyama. The majority of the
      dermatologists saw their first case between 2001 and 2003. When the patients were
      grouped according to contact sports, judo players formed the largest group,
      followed by wrestlers. When grouped according to age, high school students formed
      the largest group, but the endemic had also expanded among junior high school
      students and adults, and there was one nursery school child who was a member of a
      judo club. Seventy-four of the dermatologists were sent sterilized hairbrushes to
      collect samples from patients suspected as having tinea capitis during July and
      September 2004. Trichophyton tonsurans was detected in samples from 6 patients.
      To investigate the molecular epidemiology, 71 of the clinical strains of T.
      tonsurans isolated from the Hokuriku and Kinki regions were analyzed using
      restriction fragment length polymorphisms of the non-transcribed spacer regions
      of ribosomal RNA genes. With the restriction enzyme Mva I, two molecular types
      were detected among the strains, indicating that the causative agents of the
      endemic were derived from different origins.

PMID- 15864256
TI  - [Survey of Trichophyton tonsurans Infection in the Kyushu, Chugoku and Shikoku
      areas of Japan].
AB  - A survey on the infestation of dermatophytosis caused by T. tonsurans was made by
      inquiry to dermatologists. Patients strongly suggestive of having skin lesions
      due to T. tonsurans were seen in all areas examined, and were mainly schoolboys,
      including those practicing judo, of high schools and junior high schools. In
      Nagasaki, a mycological examination was done on 21 judo students and their
      teacher in a high school in which a patient with T. tonsurans infection was
      mycologically confirmed and treated by antimycotics. Mycological examinations
      failed to isolate T. tonsurans, but even after the examination sporadic cases
      were reported among the group members. In Saga prefecture, Kyushu, a mycological
      screening for T. tonsurans infection among judoists and wrestlers in 13 high
      schools and 7 junior high schools was done using the blush sampling method. Fifty
      six strains of T. tonsurans were isolated from 248 students. The problems
      concerning the control of this infection were discussed.

PMID- 15864257
TI  - The Pathogenicity of Stachybotrys chartarum.
AB  - Stachybotrys chartarum is a dematiaceous fungus that is ubiquitous in our living
      environment. This fungus has long been regarded as non-pathogenic and its
      inhalation effect on humans has been scarcely studied. Recently, however,
      epidemiologic studies on acute idiopathic pulmonary hemorrhage in infants
      suggested that the fungus might be potentially pathogenic to humans. To determine
      the pathogenicity of this fungus, its interaction with the host defense system
      was studied using polymorphonuclear leukocytes (PMNs) and macrophages.
      Histopathological analysis of mice intratracheally injected with this fungus was
      also performed. The results disclosed that the conidia of S. chartarum were
      resistant to the antifungal activities of alveolar macrophages in terms of
      phagocytosis, killing and inhibition of germination. However, the conidia could
      not survive in the lungs of mice when injected intratracheally. Lavage fluid of
      mycelia that contained the dark slimy material coating the surface of conidia
      showed cytotoxic activity against macrophages and PMNs. Intratracheal injection
      of conidia in mice resulted in intraalveolar infiltration of PMNs. When using
      multiple injections during a 3-week period, strong eosinophilic infiltration into
      the proximal alveoli and perivascular tissues was observed. Our results suggest
      that inhalation of conidia may cause serious damage to the human lung,
      particularly when repeated.

PMID- 15864258
TI  - [An investigation of Trichophyton tonsurans infection in university students
      participating in sports clubs].
AB  - BACKGROUND: The prevalence of the infectious disease Trichophyton tonsurans is
      rapidly increasing in Japan, particularly in athletes of these sports such as
      judo. Recognition of the current prevalence of this disease not only in athletes
      of these sports but also in other athletes is important to prevent its further
      spread. SUBJECTS AND METHODS: In November, 2002 we used a questionnaire survey
      and hairbrush culture to identify hair dermatophyte carriers among 31 members of
      a university judo club. The dermatophyte carriers received antimycotic therapy,
      and all participants were taught infection prevention. Repeat screenings of the
      judo club members were performed 9 times over the following 18-month period. In
      addition, from November, 2003 to February, 2004 we screened 466 students of other
      university sports clubs for hair dermatophytes using the questionnaire survey and
      hairbrush culture technique. RESULTS: (1) Initially, we identified 11 (35%) of 31
      members of the judo club as dermatophyte-positive by hairbrush culture. These
      dermatophyte carriers received antimycotic therapy, and implementation of
      infection prevention measures by all club members was initiated. Members
      continued to participate in matches and group judo practices under daily
      instructions for infection prevention. Tests performed on 9 occasions over a 1.5
      year period following the initial testing showed all members of the judo club to
      be dermatophyte-negative and with no signs of tinea corporis. (2) Using a
      questionnaire and the hairbrush culture technique, we screened 466 members of
      other sports clubs, including 138 students who had weekly judo lessons and 185
      students who were living in a dormitory. All were dermatophyte-negative by
      hairbrush culture, and no participant acknowledged any history or presence of
      eruptions suggestive of tinea. CONCLUSIONS: Our investigation suggests that the
      current spread of T. tonsurans infection in Japan is occurring mainly in athletes
      of high-contact sports such as judo. The successful control of this disease by
      the judo club in our university suggests that spread of the infection can be
      prevented without requiring that training be discontinued in a group fully
      informed about the disease.

PMID- 15864259
TI  - Evaluation of a newly developed identification kit, RID Zyme CAS test, for
      Candida albicans.
AB  - To evaluate a newly developed identification kit, the RID Zyme CAS test for
      Candida albicans, 1136 C. albicans and 403 non-albicans Candida strains were
      tested. Distinction of medically important non-albicans strains, with the
      exception of C. dubliniensis, was obtained. These results show that this new kit
      is simple and effective for the identification of C. albicans in clinical
      samples. Furthermore, the one hour period for identification makes it very
      attractive.

PMID- 15864260
TI  - Identification of Trichophyton rubrum by nested PCR analysis from paraffin
      embedded specimen in trichophytia profunda acuta of the glabrous skin.
AB  - Trichophytia profunda acuta of the glabrous skin (TPAGS) arose in a 67-year-old
      Japanese man. The patient presented indurated erythematous plaques and nodules on
      his left forearm. Direct microscopic examination of the scale in KOH preparation
      was negative for fungal elements, and culture for dermatophytes was also
      negative. Although fungal infection could not be proven in hematoxillin-eosin
      stained sections, deep-cut sections of the biopsied skin lesion with PAS stain
      revealed the ectothrix presence of fungal elements. Nested PCR was done with
      Trichophyton specific primers directed to internal transcribed spacer gene 1
      (ITS1), using template DNA obtained from formalin fixed, paraffin embedded skin
      sections. A single band corresponding to T. rubrum was obtained, and the
      etiological agent was thus identified. KOH tests and cultures may often turn out
      unsuccessful, perhaps reflecting the hair follicle dominant fungus growth in
      TPAGS. Although these tests are most important for diagnosis of TPAGS, nested PCR
      using paraffin embedded skin sections may be an alternative method to identify
      the etiological agent.

PMID- 15864261
TI  - Genetic diversity of the internal transcribed spacers (ITS) and 5.8S rRNA genes
      among the clinical isolates of Candida parapsilosis in Brazil and Japan.
AB  - The internal transcribed spacer (ITS) region including 5.8S rDNA sequences of 58
      isolates of Candida parapsilosis in Brazil and Japan was analyzed. Although most
      of the C. parapsilosis strains tested were confirmed to belong to three already
      reported genetically distinct groups (I, II and III) based on their ITS region
      sequences, 5 strains of the Brazilian isolates showed different sequences from
      those heretofore reported and suggested a presence of new genotype. For these
      strains of C. parapsilosis, we proposed a new genetic group (IV). The sequence
      similarities of this new group of IV to I, II and III were 87.4%, 94.7% and 87.3%
      in the ITS1 region, respectively. Genetic diversity in ITS regions of the
      remaining C. parapsilosis strains in Brazil and Japan was also discussed.

PMID- 15864262
TI  - Prokaryotic toxin-antitoxin stress response loci.
AB  - Although toxin-antitoxin gene cassettes were first found in plasmids, recent
      database mining has shown that these loci are abundant in free-living
      prokaryotes, including many pathogenic bacteria. For example, Mycobacterium
      tuberculosis has 38 chromosomal toxin-antitoxin loci, including 3 relBE and 9
      mazEF loci. RelE and MazF are toxins that cleave mRNA in response to nutritional
      stress. RelE cleaves mRNAs that are positioned at the ribosomal A-site, between
      the second and third nucleotides of the A-site codon. It has been proposed that
      toxin-antitoxin loci function in bacterial programmed cell death, but evidence
      now indicates that these loci provide a control mechanism that helps free-living
      prokaryotes cope with nutritional stress.

PMID- 15864263
TI  - Making 'sense' of metabolism: autoinducer-2, LuxS and pathogenic bacteria.
AB  - Bacteria exploit many mechanisms to communicate with each other and their
      surroundings. Mechanisms using small diffusible signals to coordinate behaviour
      with cell density (quorum sensing) frequently contribute to pathogenicity.
      However, pathogens must also be able to acquire nutrients and replicate to
      successfully invade their host. One quorum-sensing system, based on the
      possession of LuxS, bears the unique feature of contributing directly to
      metabolism, and therefore has the potential to influence both gene regulation and
      bacterial fitness. Here, we discuss the influence that LuxS and its product,
      autoinducer-2, have on virulence, relating the current evidence to the preferred
      niche of the pathogen and the underlying mechanisms involved.

PMID- 15864264
TI  - The versatile roles of antibodies in Borrelia infections.
AB  - Antibodies are the primary weapons of the mammalian immune system that are used
      against the tick-borne borreliae, the causative agents of relapsing fever and
      Lyme disease worldwide. Some antibody responses have 'traditional' functions,
      whereas others are more versatile and have novel functions and modes of action.
      At a time when the multiple functions of antibodies are being increasingly
      recognized and passive immunization is being revived as therapy for infectious
      and other diseases, the versatile nature of the antibody response to the
      borreliae fits well with this antibody renaissance.

PMID- 15864265
TI  - Identifying microorganisms responsible for ecologically significant
      biogeochemical processes.
AB  - Throughout evolutionary time, and each day in every habitat throughout the globe,
      microorganisms have been responsible for maintaining the biosphere. Despite the
      crucial part that they play in the cycling of nutrients in habitats such as
      soils, sediments and waters, only rarely have the microorganisms actually
      responsible for key processes been identified. Obstacles that have traditionally
      impeded fundamental microbial ecology inquiries are now yielding to technical
      advancements that have important parallels in medical microbiology. The pace of
      new discoveries that document ecological processes and their causative agents
      will no doubt accelerate in the near future, and might assist in ecosystem
      management.

PMID- 15864266
TI  - Cancer drug discovery through collaboration.
AB  - It has been two decades since cancer was first described as a genetic disease and
      researchers offered the promise of early diagnosis and targeted therapies. Today,
      most cancer patients still await life-saving treatments. Genomics and other '
      omics' technologies have revealed a complexity among cancers that makes almost
      any tumour genetically unique; as a consequence, effective targeted therapies
      might be suitable only for small subgroups of patients. We suggest that by
      merging and organizing their core competencies, academia, biotechnology companies
      and the pharmaceutical industry can address existing bottlenecks in anticancer
      drug discovery and development.

PMID- 15864267
TI  - The rise and rise of drug delivery.
AB  - Drug delivery has typically focused on optimizing marketed compounds, improving
      their effectiveness or tolerability, and simplifying their administration. This
      role now includes the first biopharmaceuticals as well as more conventional
      drugs. As drug-delivery technologies come into play earlier in the development
      cycle, however, they can also enhance the screening and evaluation of new
      compounds and 'rescue' failed compounds, such as those with low solubility. In
      this article, we look back at how the burgeoning field of drug delivery came into
      being and describe approaches for future discovery and development.

PMID- 15864268
TI  - Rho kinase, a promising drug target for neurological disorders.
AB  - Rho kinases (ROCKs), the first Rho effectors to be described, are
      serine/threonine kinases that are important in fundamental processes of cell
      migration, cell proliferation and cell survival. Abnormal activation of the
      Rho/ROCK pathway has been observed in various disorders of the central nervous
      system. Injury to the adult vertebrate brain and spinal cord activates ROCKs,
      thereby inhibiting neurite growth and sprouting. Inhibition of ROCKs results in
      accelerated regeneration and enhanced functional recovery after spinal-cord
      injury in mammals, and inhibition of the Rho/ROCK pathway has also proved to be
      efficacious in animal models of stroke, inflammatory and demyelinating diseases,
      Alzheimer's disease and neuropathic pain. ROCK inhibitors therefore have
      potential for preventing neurodegeneration and stimulating neuroregeneration in
      various neurological disorders.

PMID- 15864269
TI  - Regulators of apoptosis: suitable targets for immune therapy of cancer.
AB  - Harnessing the immune system in the battle against cancer has been the focus of
      tremendous research efforts during the past two decades. Several means for
      achieving this goal, including adoptive transfer of tumour-reactive T cells,
      systemic or localized administration of immune modulating cytokines and the use
      of 'therapeutic' vaccines, have been explored. Anti-apoptotic molecules that
      enhance the survival of cancer cells and facilitate their escape from cytotoxic
      therapies represent prime candidates as vaccination antigens. Notably,
      spontaneous cellular immune responses against these proteins have frequently been
      identified in cancer patients. Here, we summarize current knowledge of IAP and
      BCL2 family proteins as T-cell antigens, report the results of the first
      explorative trial using these antigens in therapeutic vaccinations against cancer
      and discuss future opportunities.

PMID- 15864270
TI  - Elucidating mechanisms of drug-induced toxicity.
AB  - The early and high-throughput application of assays for non-genetic toxicity is
      of great interest to the pharmaceutical industry, although few systems have been
      validated as being of good predictive value. New technologies could enable
      toxicity to be studied in the context of systems biology. An important factor to
      be considered is the metabolism of drugs to reactive intermediates. Chemical
      reactions of these with cell and tissue nucleophiles are relatively well
      understood, but predicting how biological modifications will affect signalling
      and regulatory networks remains a challenge. Some of these pathways could be
      useful as sentinels for toxicity. This article will cover some examples of drug
      toxicity and the prospects for future technology development.

PMID- 15864271
TI  - Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors.
AB  - Poly(ADP-ribose) polymerases (PARPs) are involved in the regulation of many
      cellular functions. Three consequences of the activation of PARP1, which is the
      main isoform of the PARP family, are particularly important for drug development:
      first, its role in DNA repair; second, its capacity to deplete cellular energetic
      pools, which culminates in cell dysfunction and necrosis; and third, its capacity
      to promote the transcription of pro-inflammatory genes. Consequently,
      pharmacological inhibitors of PARP have the potential to enhance the cytotoxicity
      of certain DNA-damaging anticancer drugs, reduce parenchymal cell necrosis (for
      example, in stroke or myocardial infarction) and downregulate multiple
      simultaneous pathways of inflammation and tissue injury (for example, in
      circulatory shock, colitis or diabetic complications). The first ultrapotent
      novel PARP inhibitors have now entered human clinical trials. This article
      presents an overview of the principal pathophysiological pathways and mechanisms
      that are governed by PARP, followed by the main structures and therapeutic
      actions of various classes of novel PARP inhibitors.

PMID- 15864272
TI  - Mechanisms of type-I- and type-II-interferon-mediated signalling.
AB  - Interferons are cytokines that have antiviral, antiproliferative and
      immunomodulatory effects. Because of these important properties, in the past two
      decades, major research efforts have been undertaken to understand the signalling
      mechanisms through which these cytokines induce their effects. Since the original
      discovery of the classical JAK (Janus activated kinase)-STAT (signal transducer
      and activator of transcription) pathway of signalling, it has become clear that
      the coordination and cooperation of multiple distinct signalling cascades -
      including the mitogen-activated protein kinase p38 cascade and the
      phosphatidylinositol 3-kinase cascade - are required for the generation of
      responses to interferons. It is anticipated that an increased understanding of
      the contributions of these recently identified pathways will advance our current
      thinking about how interferons work.

PMID- 15864273
TI  - Anatomy of CD1-lipid antigen complexes.
AB  - CD1 proteins bind lipids to form antigen complexes that contact T-cell receptors
      and activate T cells. Recent crystal structures of CD1 proteins show that their
      antigen-binding grooves are composed of up to four pockets (A', C', F' and T')
      and two antigen portals (C' and F'). Although certain structural features are
      conserved among CD1 proteins, the grooves of CD1a, CD1b and CD1d differ in the
      number, shape and connectivity of their antigen-binding pockets. Here, we outline
      how the portals and pockets of CD1 antigen-binding grooves influence ligand
      specificity and facilitate the presentation of a surprisingly diverse set of
      antigenic lipids, glycolipids, lipopeptides and even small, non-lipidic
      molecules.

PMID- 15864274
TI  - Cannabinoid-based drugs as anti-inflammatory therapeutics.
AB  - In the nineteenth century, marijuana was prescribed by physicians for maladies
      ranging from eating disorders to rabies. However, as newer, more effective drugs
      were discovered and as the potential for abuse of marijuana was recognized, its
      use as a therapeutic became restricted, and only recently has its therapeutic
      potential been re-evaluated. Recent studies in animal models and in humans have
      produced promising results for the treatment of various disorders - such as
      obesity, cancer, and spasticity and tremor due to neuropathology - with drugs
      based on marijuana-derived cannabinoids. Moreover, as I discuss here, a wealth of
      information also indicates that these drugs have immunosuppressive and anti
      inflammatory properties; therefore, on the basis of this mode of action, the
      therapeutic usefulness of these drugs in chronic inflammatory diseases is now
      being reassessed.

PMID- 15864275
TI  - A worm's eye view of the immune system: consequences for evolution of human
      autoimmune disease.
AB  - Humans and the many parasites that we can host have co-evolved over millions of
      years. This has been compared to an arms race in which the immune armoury of the
      human has evolved to deal with potential pathogens and the pathogen has evolved
      strategies to evade, and in some cases use, the immune system of the human host.
      Recently, there have been marked changes in the exposure of individuals in the
      developed world to both microorganisms and metazoan parasites, so the immune
      stimuli such organisms provide no longer have a role in our lives. As we discuss
      here, this is a marked perturbation, and the absence of the associated
      immunomodulation might have led to the increased emergence of autoimmune
      diseases.

PMID- 15864276
TI  - ERBB receptors and cancer: the complexity of targeted inhibitors.
AB  - ERBB receptor tyrosine kinases have important roles in human cancer. In
      particular, the expression or activation of epidermal growth factor receptor and
      ERBB2 are altered in many epithelial tumours, and clinical studies indicate that
      they have important roles in tumour aetiology and progression. Accordingly, these
      receptors have been intensely studied to understand their importance in cancer
      biology and as therapeutic targets, and many ERBB inhibitors are now used in the
      clinic. We will discuss the significance of these receptors as clinical targets,
      in particular the molecular mechanisms underlying response.

PMID- 15864277
TI  - Ovarian cancer metastasis: integrating insights from disparate model organisms.
AB  - Despite considerable efforts to improve early detection, and advances in
      chemotherapy, metastasis remains a major challenge in the clinical management of
      ovarian cancer. Studies of new murine models are providing novel insights into
      the pathophysiology of ovarian cancer, but these models are not readily amenable
      to genetic screens. Genetic analysis of border-cell migration in the Drosophila
      melanogaster ovary provides clues that will improve our understanding of ovarian
      cancer metastasis at the molecular level, and also might lead to potential
      therapeutic targets.

PMID- 15864278
TI  - Molecular genetics of multiple endocrine neoplasia types 1 and 2.
AB  - Six multiple endocrine neoplasia (MEN) syndromes have received a level of
      attention that might seem disproportionate to their low prevalence. The attention
      has been given because their hormonal excesses cause striking metabolic
      expressions and because they might clarify pathways disrupted in more common
      tumours. The recent discovery of the main gene in each MEN syndrome has furthered
      our understanding of not only hereditary but also sporadic tumours and has
      fostered new avenues of research.

PMID- 15864279
TI  - The RUNX genes: gain or loss of function in cancer.
AB  - The RUNX genes have come to prominence recently because of their roles as
      essential regulators of cell fate in development and their paradoxical effects in
      cancer, in which they can function either as tumour-suppressor genes or dominant
      oncogenes according to context. How can this family of transcription factors have
      such an ambiguous role in cancer? How and where do these genes impinge on the
      pathways that regulate growth control and differentiation? And what is the
      evidence for a wider role for the RUNX genes in non-haematopoietic cancers?

PMID- 15864280
TI  - The Nurses' Health Study: lifestyle and health among women.
AB  - The Nurses' Health Study has grown from a simple questionnaire-based study
      initiated in 1976 to a rich resource of information collected over 29 years.
      Important details about lifestyle have been collected throughout the study and,
      as the study has progressed, blood samples and DNA from buccal cells have been
      collected and stored. Tumour samples have also been collected from participants
      who developed cancer. Through analyses that integrate information from these
      various sources we are advancing our understanding of the causes of cancer and
      the potential for prevention.

PMID- 15864281
TI  - Immunotherapy and chemotherapy--a practical partnership.
AB  - This article discusses how recent data have altered the way we understand how
      dying tumour cells, particularly those killed by chemotherapy, engage with
      antitumour immune responses. These data have significant implications for the
      development of new protocols combining chemotherapy with immunotherapy,
      indicating an exciting potential for therapeutic synergy with general
      applicability to many cancer types.

PMID- 15864282
TI  - Post-prenylation-processing enzymes as new targets in oncogenesis.
AB  - RAS and many other oncogenic proteins undergo a complex series of post
      translational modifications that are initiated by the addition of an isoprenoid
      lipid through a process known as prenylation. Following prenylation, these
      proteins usually undergo endoproteolytic processing by the RCE1 protease and then
      carboxyl methylation by a unique methyltransferase known as isoprenylcysteine
      carboxyl methyltransferase (ICMT). Although inhibitors that have been designed to
      target the prenylation step are now in advanced-stage clinical trials, their
      utility and efficacy seem to be limited. Recent findings, however, indicate that
      the inhibition of these post-prenylation-processing steps--particularly that of
      ICMT-catalysed methylation--might provide a better approach to the control of
      cancer-cell proliferation.

PMID- 15864283
TI  - Is the system dumbing down research?

PMID- 15864284
TI  - Landscape fragmentation, biodiversity loss and the societal response. The long
      term consequences of our use of natural resources may be surprising and
      unpleasant.

PMID- 15864285
TI  - Scientists and the marketplace of opinions. Scientific credibility takes on a
      different meaning when reaching out to the public.

PMID- 15864286
TI  - Genome coverage, literally speaking. The challenge of annotating 200 genomes with
      4 million publications.

PMID- 15864287
TI  - Aptitude or attitude? Lawrence Summers' recent remarks reflect what little
      progress has been made in the public's understanding why women are under
      represented in science.

PMID- 15864288
TI  - Engendering creativity in the biomedical sciences. Innovation can be stifled
      inadvertently or intentionally. Fortunately there are several ways in which
      scientists can foster creativity.

PMID- 15864289
TI  - Is political correctness damaging science? Peer pressure and mainstream thinking
      may discourage novelty and innovation.

PMID- 15864290
TI  - Cell adhesion and signal transduction in cancer. Conference on cadherins,
      catenins and cancer.

PMID- 15864291
TI  - Microbial strategies to exploit host cells. Meeting on spatial and temporal
      dynamics of the endomembrane system.

PMID- 15864292
TI  - Membrane curvature sorts lipids. Stabilized lipid rafts in membrane transport.

PMID- 15864293
TI  - Single translation--dual destination: mechanisms of dual protein targeting in
      eukaryotes.
AB  - It is well documented that single eukaryotic genes can give rise to proteins that
      are localized to several subcellular locations. This is achieved at the level of
      transcription, splicing and translation, and results in two or more translation
      products that either harbour or lack specific targeting signals. Nevertheless,
      the possibility of dual targeting of a single translation product has recently
      emerged. Here, we review cases of such dual targeting with emphasis on the
      mechanisms through which these phenomena occur. Proteins that harbour one signal,
      two separate signals or an overlapping ambiguous signal may follow dual
      distribution in the cell. The mechanism of dual targeting is driven by the
      competition or promiscuity of various molecular events. Protein folding, post
      translational modification and protein-protein interaction are key players in
      this phenomenon.

PMID- 15864294
TI  - Replacement of K-Ras with H-Ras supports normal embryonic development despite
      inducing cardiovascular pathology in adult mice.
AB  - Ras proteins are highly related GTPases that have key roles in regulating growth,
      differentiation and tumorigenesis. Gene-targeting experiments have shown that,
      out of the three mammalian ras genes, only K-ras is essential for normal mouse
      embryogenesis, and that mice deprived of H-ras and/or N-ras show no major
      phenotype. We generated mice (HrasKI) in which the K-ras gene had been modified
      to encode H-Ras protein. HrasKI mice produce undetectable amounts of K-Ras but-in
      contrast to mice homozygous for a null K-ras allele-they are born at the expected
      mendelian frequency, indicating that H-Ras can be substituted for K-Ras in
      embryonic development. However, adult HrasKI mice show dilated cardiomyopathy
      associated with arterial hypertension. Our results show that K-Ras can be
      replaced by H-Ras in its essential function in embryogenesis, and indicate that K
      Ras has a unique role in cardiovascular homeostasis.

PMID- 15864295
TI  - hMRE11 deficiency leads to microsatellite instability and defective DNA mismatch
      repair.
AB  - DNA mismatch repair (MMR) is essential in the surveillance of accurate
      transmission of genetic information, and defects in this pathway lead to
      microsatellite instability and hereditary nonpolyposis colorectal cancer (HNPCC).
      Our previous study raised the possibility that hMRE11 might be involved in MMR
      through physical interaction with hMLH1. Here, we show that hMRE11 deficiency
      leads to significant increase in MSI for both mono- and dinucleotide sequences.
      Furthermore, RNA-interference-mediated hMRE11-knockdown in HeLa cells results in
      MMR deficiency. Analysis of seven HNPCC-associated hMLH1 missense mutations
      located within the hMRE11-interacting domain shows that four mutations (L574P,
      K618T, R659P and A681T) cause near-complete disruption of the interaction between
      hMRE11 and hMLH1, and two mutations (Q542L and L582V) cause a 30% reduction of
      protein interaction. These findings indicate that hMRE11 represents a functional
      component of the MMR pathway and the disruption of hMLH1-hMRE11 interaction could
      be an alternative molecular explanation for hMLH1 mutations in a subset of HNPCC
      tumours.

PMID- 15864296
TI  - Dissociation of heterochromatin protein 1 from lamin B receptor induced by human
      polyomavirus agnoprotein: role in nuclear egress of viral particles.
AB  - The nuclear envelope is one of the chief obstacles to the translocation of
      macromolecules that are larger than the diameter of nuclear pores.
      Heterochromatin protein 1 (HP1) bound to the lamin B receptor (LBR) is thought to
      contribute to reassembly of the nuclear envelope after cell division. Human
      polyomavirus agnoprotein (Agno) has been shown to bind to HP1alpha and to induce
      its dissociation from LBR, resulting in destabilization of the nuclear envelope.
      Fluorescence recovery after photobleaching showed that Agno increased the lateral
      mobility of LBR in the inner nuclear membrane. Biochemical and immunofluorescence
      analyses showed that Agno is targeted to the nuclear envelope and facilitates the
      nuclear egress of polyomavirus-like particles. These results indicate that
      dissociation of HP1alpha from LBR and consequent perturbation of the nuclear
      envelope induced by polyomavirus Agno promote the translocation of virions out of
      the nucleus.

PMID- 15864297
TI  - A mitogen-activated protein kinase regulates male gametogenesis and transmission
      of the malaria parasite Plasmodium berghei.
AB  - Differentiation of malaria parasites into sexual forms (gametocytes) in the
      vertebrate host and their subsequent development into gametes in the mosquito
      vector are crucial steps in the completion of the parasite's life cycle and
      transmission of the disease. The molecular mechanisms that regulate the sexual
      cycle are poorly understood. Although several signal transduction pathways have
      been implicated, a clear understanding of the pathways involved has yet to
      emerge. Here, we show that a Plasmodium berghei homologue of Plasmodium
      falciparum mitogen-activated kinase-2 (Pfmap-2), a gametocyte-specific mitogen
      activated protein kinase (MAPK), is required for male gamete formation. Parasites
      lacking Pbmap-2 are competent for gametocytogenesis, but exflagellation of male
      gametocytes, the process that leads to male gamete formation, is almost entirely
      abolished in mutant parasites. Consistent with this result, transmission of
      mutant parasites to mosquitoes is grossly impaired. This finding identifies a
      crucial role for a MAPK pathway in malaria transmission.

PMID- 15864298
TI  - A gating mutation at the internal mouth of the Kir6.2 pore is associated with
      DEND syndrome.
AB  - Inwardly rectifying potassium (Kir) channels control cell membrane K+ fluxes and
      electrical signalling in diverse cell types. Heterozygous mutations in the human
      Kir6.2 gene (KCNJ11), the pore-forming subunit of the ATP-sensitive (K(ATP))
      channel, cause permanent neonatal diabetes mellitus. However, the I296L mutation
      also results in developmental delay, muscle weakness and epilepsy. We
      investigated the functional effects of the I296L mutation by expressing wild-type
      or mutant Kir6.2/SUR1 channels in Xenopus oocytes. The mutation caused a marked
      increase in resting whole-cell K(ATP) currents by reducing channel inhibition by
      ATP, in both homomeric and simulated heterozygous states. Kinetic analysis showed
      that the mutation impaired ATP sensitivity indirectly, by stabilizing the open
      state of the channel and possibly also by means of an allosteric effect on ATP
      binding and/or transduction. The results implicate a new region in Kir-channel
      gating and suggest that disease severity is correlated with the extent of
      reduction in ATP sensitivity.

PMID- 15864299
TI  - Direct measurement of protein energy landscape roughness.
AB  - The energy landscape of proteins is thought to have an intricate, corrugated
      structure. Such roughness should have important consequences on the folding and
      binding kinetics of proteins, as well as on their equilibrium fluctuations. So
      far, no direct measurement of protein energy landscape roughness has been made.
      Here, we combined a recent theory with single-molecule dynamic force spectroscopy
      experiments to extract the overall energy scale of roughness epsilon for a
      complex consisting of the small GTPase Ran and the nuclear transport receptor
      importin-beta. The results gave epsilon > 5k(B)T, indicating a bumpy energy
      surface, which is consistent with the ability of importin-beta to accommodate
      multiple conformations and to interact with different, structurally distinct
      ligands.

PMID- 15864301
TI  - Structural and mechanistic insights into the interaction between Rho and
      mammalian Dia.
AB  - Formins are involved in a variety of cellular processes that require the
      remodelling of the cytoskeleton. They contain formin homology domains FH1 and
      FH2, which initiate actin assembly. The Diaphanous-related formins form a
      subgroup that is characterized by an amino-terminal Rho GTPase-binding domain
      (GBD) and an FH3 domain, which bind somehow to the carboxy-terminal Diaphanous
      autoregulatory domain (DAD) to keep the protein in an inactive conformation. Upon
      binding of activated Rho proteins, the DAD is released and the ability of the
      formin to nucleate and elongate unbranched actin filaments is induced. Here we
      present the crystal structure of RhoC in complex with the regulatory N terminus
      of mammalian Diaphanous 1 (mDia1) containing the GBD/FH3 region, an all-helical
      structure with armadillo repeats. Rho uses its 'switch' regions for interacting
      with two subdomains of GBD/FH3. We show that the FH3 domain of mDia1 forms a
      stable dimer and we also identify the DAD-binding site. Although binding of Rho
      and DAD on the N-terminal fragment of mDia1 are mutually exclusive, their binding
      sites are only partially overlapping. On the basis of our results, we propose a
      structural model for the regulation of mDia1 by Rho and DAD.

PMID- 15864302
TI  - Structural basis for nuclear import complex dissociation by RanGTP.
AB  - Nuclear protein import is mediated mainly by the transport factor importin-beta
      that binds cytoplasmic cargo, most often via the importin-alpha adaptor, and then
      transports it through nuclear pore complexes. This active transport is driven by
      disassembly of the import complex by nuclear RanGTP. The switch I and II loops of
      Ran change conformation with nucleotide state, and regulate its interactions with
      nuclear trafficking components. Importin-beta consists of 19 HEAT repeats that
      are based on a pair of antiparallel alpha-helices (referred to as the A- and B
      helices). The HEAT repeats stack to yield two C-shaped arches, linked together to
      form a helicoidal molecule that has considerable conformational flexibility. Here
      we present the structure of full-length yeast importin-beta (Kap95p or
      karyopherin-beta) complexed with RanGTP, which provides a basis for understanding
      the crucial cargo-release step of nuclear import. We identify a key interaction
      site where the RanGTP switch I loop binds to the carboxy-terminal arch of Kap95p.
      This interaction produces a change in helicoidal pitch that locks Kap95p in a
      conformation that cannot bind importin-alpha or cargo. We suggest an allosteric
      mechanism for nuclear import complex disassembly by RanGTP.

PMID- 15864303
TI  - 3D shape perception from combined depth cues in human visual cortex.
AB  - Our perception of the world's three-dimensional (3D) structure is critical for
      object recognition, navigation and planning actions. To accomplish this, the
      brain combines different types of visual information about depth structure, but
      at present, the neural architecture mediating this combination remains largely
      unknown. Here, we report neuroimaging correlates of human 3D shape perception
      from the combination of two depth cues. We measured fMRI responses while
      observers judged the 3D structure of two sequentially presented images of slanted
      planes defined by binocular disparity and perspective. We compared the behavioral
      and fMRI responses evoked by changes in one or both of the depth cues. fMRI
      responses in extrastriate areas (hMT+/V5 and lateral occipital complex), rather
      than responses in early retinotopic areas, reflected differences in perceived 3D
      shape, suggesting 'combined-cue' representations in higher visual areas. These
      findings provide insight into the neural circuits engaged when the human brain
      combines different information sources for unified 3D visual perception.

PMID- 15864304
TI  - Endocannabinoid signaling depends on the spatial pattern of synapse activation.
AB  - The brain's endocannabinoid retrograde messenger system decreases presynaptic
      transmitter release, but its physiological function is uncertain. We show that
      endocannabinoid signaling is absent when spatially dispersed synapses are
      activated on rodent cerebellar Purkinje cells but that it reduces presynaptic
      glutamate release when nearby synapses are active. This switching of signaling
      according to the spatial pattern of activity is controlled by postsynaptic type I
      metabotropic glutamate receptors, which are activated disproportionately when
      glutamate spillover between synapses produces synaptic crosstalk. When spatially
      distributed synapses are activated, endocannabinoid inhibition of transmitter
      release can be rescued by inhibiting glutamate uptake to increase glutamate
      spillover. Endocannabinoid signaling initiated by type I metabotropic glutamate
      receptors is a homeostatic mechanism that detects synaptic crosstalk and
      downregulates glutamate release in order to promote synaptic independence.

PMID- 15864305
TI  - Sensitized RNAi screen of human kinases and phosphatases identifies new
      regulators of apoptosis and chemoresistance.
AB  - Evasion from apoptosis is a hallmark of cancer, and recent success using targeted
      therapeutics underscores the importance of identifying anti-apoptotic survival
      pathways. Here we utilize RNA interference (RNAi) to systematically screen the
      kinase and phosphatase component of the human genome. In addition to known
      kinases, we identified several new survival kinases. Interestingly, numerous
      phosphatases and associated regulatory subunits contribute to cell survival,
      revealing a previously unrecognized general role for phosphatases as negative
      regulators of apoptosis. We also identified a subset of phosphatases with tumour
      suppressor-like activity. Finally, RNAi targeting of specific protein kinases
      sensitizes resistant cells to chemotherapeutic agents. The development of
      inhibitors that target these kinases or phosphatases may lead to new anti-cancer
      strategies.

PMID- 15864306
TI  - A functional SNP in CILP, encoding cartilage intermediate layer protein, is
      associated with susceptibility to lumbar disc disease.
AB  - Lumbar disc disease (LDD) is caused by degeneration of intervertebral discs of
      the lumbar spine. One of the most common musculoskeletal disorders, LDD has
      strong genetic determinants. Using a case-control association study, we
      identified a functional SNP (1184T --> C, resulting in the amino acid
      substitution I395T) in CILP, which encodes the cartilage intermediate layer
      protein, that acts as a modulator of LDD susceptibility. CILP was expressed
      abundantly in intervertebral discs, and its expression increased as disc
      degeneration progressed. CILP colocalized with TGF-beta1 in clustering
      chondrocytes and their territorial matrices in intervertebral discs. CILP
      inhibited TGF-beta1-mediated induction of cartilage matrix genes through direct
      interaction with TGF-beta1 and inhibition of TGF-beta1 signaling. The
      susceptibility-associated 1184C allele showed increased binding and inhibition of
      TGF-beta1. Therefore, we conclude that the extracellular matrix protein CILP
      regulates TGF-beta signaling and that this regulation has a crucial role in the
      etiology and pathogenesis of LDD. Our study also adds to the list of connective
      tissue diseases that are associated with TGF-beta.

PMID- 15864307
TI  - Epigenetic status of human embryonic stem cells.
AB  - We examined the allele-specific expression of six imprinted genes and the
      methylation profiles of three imprinting control regions to assess the epigenetic
      status of human embryonic stem cells. We identified generally monoallelic gene
      expression and normal methylation patterns. During prolonged passage, one cell
      line became biallelic with respect to H19, but without loss of the gametic
      methylation imprint. These data argue for a substantial degree of epigenetic
      stability in human embryonic stem cells.

PMID- 15864308
TI  - Resurrecting ancestral alcohol dehydrogenases from yeast.
AB  - Modern yeast living in fleshy fruits rapidly convert sugars into bulk ethanol
      through pyruvate. Pyruvate loses carbon dioxide to produce acetaldehyde, which is
      reduced by alcohol dehydrogenase 1 (Adh1) to ethanol, which accumulates. Yeast
      later consumes the accumulated ethanol, exploiting Adh2, an Adh1 homolog
      differing by 24 (of 348) amino acids. As many microorganisms cannot grow in
      ethanol, accumulated ethanol may help yeast defend resources in the fruit. We
      report here the resurrection of the last common ancestor of Adh1 and Adh2, called
      Adh(A). The kinetic behavior of Adh(A) suggests that the ancestor was optimized
      to make (not consume) ethanol. This is consistent with the hypothesis that before
      the Adh1-Adh2 duplication, yeast did not accumulate ethanol for later consumption
      but rather used Adh(A) to recycle NADH generated in the glycolytic pathway.
      Silent nucleotide dating suggests that the Adh1-Adh2 duplication occurred near
      the time of duplication of several other proteins involved in the accumulation of
      ethanol, possibly in the Cretaceous age when fleshy fruits arose. These results
      help to connect the chemical behavior of these enzymes through systems analysis
      to a time of global ecosystem change, a small but useful step towards a planetary
      systems biology.

PMID- 15864309
TI  - Peptides chaperoned by heat-shock proteins are a necessary and sufficient source
      of antigen in the cross-priming of CD8+ T cells.
AB  - The form in which antigens are transferred from cancer cells or infected cells to
      antigen-presenting cells as a part of the process of priming CD8(+) T cells has
      been a longstanding unresolved issue. Intact proteins or protein fragments in the
      form of free peptides or peptides chaperoned by heat-shock protein are possible
      sources of antigen. We address this here using beta-galactosidase and ovalbumin.
      Immunization with cell lysates containing intact proteins and heat-shock protein
      peptide complexes or with cell lysates depleted of either component demonstrated
      that protein fragments chaperoned by heat-shock protein and not intact protein
      were the necessary and sufficient source of antigen transferred to antigen
      presenting cells for priming CD8(+) T cell responses.

PMID- 15864310
TI  - ROS-dependent activation of the TRAF6-ASK1-p38 pathway is selectively required
      for TLR4-mediated innate immunity.
AB  - Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved
      mitogen-activated protein 3-kinase that activates both Jnk and p38 mitogen
      activated protein kinases. Here we used ASK1-deficient mice to show that ASK1 was
      selectively required for lipopolysaccharide-induced activation of p38 but not of
      Jnk or the transcription factor NF-kappaB. ASK1 was required for the induction of
      proinflammatory cytokines dependent on Toll-like receptor 4 (TLR4) but not TLR2
      or other TLRs. Consistent with this, ASK1-deficient mice were resistant to
      lipopolysaccharide-induced septic shock. Lipopolysaccharide induced the
      production of intracellular reactive oxygen species, which was required for the
      formation of a complex of the adaptor molecule TRAF6 and ASK1 and subsequent
      activation of the ASK1-p38 pathway. Our data demonstrate that the reactive oxygen
      species-dependent TRAF6-ASK1-p38 axis is crucial for TLR4-mediated mammalian
      innate immunity.

PMID- 15864311
TI  - Dynamic recruitment of PAK1 to the immunological synapse is mediated by PIX
      independently of SLP-76 and Vav1.
AB  - T cell receptor engagement activates p21-activated kinase 1 (PAK1) through a LAT
      SLP-76-Nck-Vav-Rac-dependent pathway. A second independent pathway involving a
      GIT-PIX-PAK1 trimolecular complex is also activated by T cell receptor ligation.
      Here we show a Vav-independent pathway exists that leads to PAK1 activation. In
      addition, PAK1, PIX and GIT1 were recruited to the T cell-antigen-presenting cell
      contact site independently of SLP-76 and Vav1. PAK1 recruitment to the T cell
      antigen-presenting cell interface required interaction with PIX, which also led
      to optimal PLC-gamma1 activation and T cell receptor-dependent transcriptional
      responses. These data indicate that a pathway involving the GIT-PIX-PAK1 complex
      has a crucial function in PAK1 activation by recruiting PAK1 to the immunological
      synapse.

PMID- 15864312
TI  - Identification of MMP-1 as a putative breast cancer predictive marker by global
      gene expression analysis.
AB  - Breast cancer is the second leading cause of cancer death for women in the United
      States. In 2005, about 215,000 cases of invasive breast cancer (IBC) and 50,000
      cases of ductal carcinoma in situ will be diagnosed and 40,000 women will die of
      IBC in the US. Yet there is presently no molecular marker that can be used to
      detect a precancerous state or identify which premalignant lesions will develop
      into invasive breast cancer. Here we report the gene expression analysis of
      atypical ductal hyperplastic tissues from patients with and without a history of
      breast cancer. We identify MMP-1 as a candidate marker that may be useful for
      identification of breast lesions that can develop into cancer.

PMID- 15864313
TI  - Doxycycline attenuates and delays toxicity of the oculopharyngeal muscular
      dystrophy mutation in transgenic mice.
AB  - The muscular dystrophies are a heterogeneous group of disorders for which there
      are currently no cures. Oculopharyngeal muscular dystrophy (OPMD) is an autosomal
      dominant late-onset, progressive disease that generally presents in the fifth or
      sixth decade with dysphagia, ptosis and proximal limb weakness. OPMD is caused by
      the abnormal expansion of a (GCG)n trinucleotide repeat in the coding region of
      the poly-(A) binding protein nuclear 1 (PABPN1) gene. In unaffected individuals,
      (GCG)6 codes for the first six alanines in a homopolymeric stretch of ten
      alanines. In most individuals with OPMD this (GCG)6 repeat is expanded to (GCG)8
      13, leading to a stretch of 12-17 alanines in mutant PABPN1. PABPN1 with an
      expanded polyalanine tract forms aggregates consisting of tubular filaments
      within the nuclei of skeletal muscle fibers. We have developed a transgenic mouse
      model of OPMD that manifests progressive muscle weakness accompanied by
      intranuclear aggregates and TUNEL-stained nuclei in skeletal muscle fibers. The
      onset and severity of these abnormalities were substantially delayed and
      attenuated by doxycycline treatment, which may exert its therapeutic effect by
      reducing aggregates and by distinct antiapoptotic properties. Doxycycline may
      represent a safe and feasible therapeutic for this disease.

PMID- 15864314
TI  - ATM regulates target switching to escalating doses of radiation in the
      intestines.
AB  - Although stem cells succumbing to reproductive death are assumed to be the single
      relevant targets in radiation tissue damage, recent studies showed intestinal
      stem cell damage is conditionally linked to crypt endothelial apoptosis, defining
      a two-target model. Here we report that when mouse intestines were protected
      against microvascular apoptosis, radiation switched as the dose escalated to a
      previously unrecognized crypt stem cell target, activating ceramide synthase
      mediated apoptosis to initiate intestinal damage. Whereas ataxia telangiectasia
      mutated (ATM) kinase normally represses ceramide synthase, its derepression in
      Atm(-/-) mice increased crypt stem cell radiosensitivity 3.7-fold without
      sensitizing the microvascular response. Discovery of this intestinal
      radiosensitivity mechanism allowed design of an antisense Atm oligonucleotide
      treatment which phenocopied the Atm(-/-) mouse, reordering ceramide synthase
      mediated stem cell death to become the first-line gastrointestinal response of
      wild-type littermates. These experiments indicate that tissues operate multiple
      potential targets activated consecutively according to their inherent
      radiosensitivities that may be reordered therapeutically to control radiation
      tissue responses.

PMID- 15864315
TI  - Localization and dynamic behavior of ribosomal protein L30e.
AB  - The ribosomal protein L30e is an indispensable component of the eukaryotic 80S
      ribosome, where it is part of the large (60S) ribosomal subunit. Here, we
      determined the localization of L30e in the cryo-EM map of the 80S wheat germ (wg)
      ribosome at a resolution of 9.5 A. L30e is part of the interface between large
      and small subunits, where it dynamically participates in the formation of the two
      intersubunit bridges eB9 and B4.

PMID- 15864316
TI  - FLIP is frequently expressed in endometrial carcinoma and has a role in
      resistance to TRAIL-induced apoptosis.
AB  - The FLICE-inhibitory protein (FLIP) plays a key role in the regulation of
      apoptosis triggered by death ligands. Tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) has been shown to induce apoptosis in some types of tumor
      but not in others. To assess the possible role of FLIP in apoptosis resistance in
      endometrial carcinoma, we performed an immunohistochemical study on a tissue
      microarray composed of 95 endometrial carcinomas. We found positive signals in
      43% of the cases, as well as a significant difference in FLIP expression between
      stage I and II tumors. Moreover, we observed that endometrial carcinoma cell
      lines Ishikawa and KLE did not undergo apoptosis after TRAIL treatment.
      Cotreatment of these cells with the inhibitor of transcription actinomycin D
      resulted in a dramatic decrease in cell viability and induced activation of
      caspase-8. These events coincided with downregulation of FLIP mRNA and protein.
      Inhibitors of caspase-8 or overexpression of FLIP completely blocked apoptosis
      induced by actinomycin D plus TRAIL cotreatment. More importantly, downregulation
      of endogenous FLIP expression by specific siRNAs sensitized endometrial carcinoma
      cells to TRAIL-induced apoptosis in the absence of actinomycin D. Taken together,
      our results suggest for the first time a critical role for FLIP in the regulation
      apoptosis triggered by TRAIL in endometrial carcinoma cells.

PMID- 15864317
TI  - Patterns of gene amplification in gastrointestinal stromal tumors (GIST).
AB  - Gastrointestinal stromal tumors (GIST) are the most common primary mesenchymal
      tumors of the gastrointestinal tract (GIT). They represent a wide clinico
      pathological spectrum of tumors. No single histological or clinical parameter can
      predict the prognosis while the response to therapy is related to the type of KIT
      or PDGFRA mutation. Cytogenetic and CGH studies have identified frequent gross
      chromosomal aberrations but the target genes of these changes are unknown. To
      determine whether known oncogenes take part in genomic rearrangements and to
      investigate the potential clinical significance of their amplifications, nine
      known oncogenes (CMYC, MDM2, GLI1, CDK4, HER2, EGFR1, CCND1, FGF3, EMS) were
      analyzed by fluorescent in situ hybridization (FISH) on a tissue microarray (TMA)
      containing 94 primary GIST. Clinical follow-up information was available for 57
      of these patients. Amplification was found for CMYC in three of 90 (3.3%), for
      MDM2 in five of 94 (5.3%), for EGFR1 in five of 94 (5.3%), and for CCND1 in seven
      of 79 (8.9%) evaluable cases. No amplifications were seen for HER2, GLI1, CDK4,
      FGF3, and EMS. Amplifications of MDM2 and CCND1 were associated with clinical and
      histological malignancy. In conclusion, our data show that gene amplification
      does occur in a subset of GIST. Identification of MDM2/CCND1 amplification may
      represent another molecular feature that could help in the evaluation of the
      behavior of GISTs.

PMID- 15864318
TI  - Combination treatment significantly enhances the efficacy of antitumor therapy by
      preferentially targeting angiogenesis.
AB  - Radiotherapy is one of the most widely used cancer treatments, but it is often
      unsuccessful due to the development of radioresistance by tumor cells and
      endothelial cells (ECs) lining the tumor blood vessels. We have previously shown
      that ECs are protected against ionizing irradiation primarily via the activation
      of the phosphoinositide 3-kinase (PI3 K)-Akt-Bcl-2 survival pathway. Here we
      report that combination treatment with low doses of PI3 K inhibitor (LY294002),
      cisplatin and gamma-irradiation resulted in significantly higher (61%) EC death
      as compared to each agent used alone (17, 17 and 11%, respectively). This
      combination treatment was equally effective in inducing tumor cell death (72%).
      Combination treatment also significantly inhibited EC tube formation in Matrigel
      (75%) as compared to each of the agents used alone (8, 8 and 18% for LY294002,
      cisplatin and gamma-irradiation, respectively). In our in vivo severe combined
      immunodeficient mouse model of human tumor growth and angiogenesis, combination
      treatment with low doses of LY294002, cisplatin and irradiation significantly
      inhibited the growth of human oral squamous carcinoma (OSCC-3) as well as
      prostate cancer (LnCap). The combination therapy was also very effective in
      inhibiting tumor angiogenesis where it showed a greater than 90% decrease in
      neovascularization. In contrast, combination treatment showed only a 29%
      inhibition of physiological angiogenesis. Taken together, these results suggest a
      potentially novel strategy to overcome the resistance in ECs lining tumor blood
      vessels, thereby enhancing the effectiveness of the radiation and chemotherapy.
      Moreover, this strategy of using a combination of low doses of PI3K/Akt
      inhibitor, cisplatin and radiation has the potential of significantly decreasing
      untoward side effects associated with the maximum tolerated doses of radiation
      and chemotherapy while maintaining their therapeutic efficacy.

PMID- 15864319
TI  - Intermediate studies on refolding of arginine kinase denatured by guanidine
      hydrochloride.
AB  - The refolding course and intermediate of guanidine hydrochloride (GuHCl)
      denatured arginine kinase (AK) were studied in terms of enzymatic activity,
      intrinsic fluorescence, 1-anilino-8-naphthalenesulfonte (ANS) fluorescence, and
      far-UV circular dichroism (CD). During AK refolding, the fluorescence intensity
      increased with a significantly blue shift of the emission maximum. The molar
      ellipticity of CD increased to close to that of native AK, as compared with the
      fully unfolded AK. In the AK refolding process, 2 refolding intermediates were
      observed at the concentration ranges of 0.8-1.0 mol/L and 0.3-0.5 mol GuHCl/L.
      The peak position of the fluorescence emission and the secondary structure of
      these conformation states remained roughly unchanged. The tryptophan fluorescence
      intensity increased a little. However, the ANS fluorescence intensity
      significantly increased, as compared with both the native and the fully unfolded
      states. The first refolding intermediate at the range of 0.8-1.0 mol GuHCl/L
      concentration represented a typical "pre-molten globule state structure" with
      inactivity. The second one, at the range of 0.3-0.5 mol GuHCl/L concentration,
      shared many structural characteristics of native AK, including its secondary and
      tertiary structure, and regained its catalytic function, although its activity
      was lower than that of native AK. The present results suggest that during the
      refolding of GuHCl-denatured AK there are at least 2 refolding intermediates; as
      well, the results provide direct evidence for the hierarchical mechanism of
      protein folding.

PMID- 15864320
TI  - Use of conformationally restricted pyridinium alpha-D-N-acetylneuraminides to
      probe specificity in bacterial and viral sialidases.
AB  - Investigations into subtle changes in the catalytic activity of sialidases have
      been performed using enzymes from several different origins, and their results
      have been compared. This work highlights the potential pitfalls encountered when
      extending conclusions derived from mechanistic studies on a single enzyme even to
      those with high-sequence homology. Specifically, a panel of 5 pyridinium N
      acetylneuraminides were used as substrates in a study that revealed subtle
      differences in the catalytic mechanisms used by 4 different sialidase enzymes.
      The lowest reactivity towards the artificial (pyridinium) substrates was
      displayed by the Newcastle disease virus hemagglutinin-neuraminidase. Moreover,
      in reactions involving aryl N-acetylneuraminides, the activity of the Newcastle
      enzyme was competitively inhibited by the 3,4-dihydro-2H-pyrano[3,2-c]pyridinium
      compound with a Ki = 58 micromol/L. Alternatively, the 3 bacterial enzymes
      tested, from Salmonella typhimurium, Clostridium perfringens, and Vibrio
      cholerae, were catalytically active against all members of the panel of
      substrates. Based on the observed effect of leaving-group ability, it is proposed
      that the rate-determining step for kcat (and likely for kcat/Km as well) with
      each bacterial enzyme is as follows: sialylation, which is concerted with
      conformational change for V. cholerae; and conformational change for S.
      typhimurium and C. perfringens.

PMID- 15864321
TI  - Phospholipase C-beta1 mediates alpha1-adrenergic receptor-stimulated activation
      of the sodium-hydrogen exchanger in Chinese hamster lung fibroblasts (CCL39).
AB  - The activation of the Na+-H+ exchanger 1 (NHE1) and extracellular-signal
      regulated kinase (ERK) phosphorylation in Chinese hamster lung fibroblasts
      (CCL39) was characterized in response to the specific alpha1-adrenergic agonist,
      phenylephrine (PE). Addition of 100 micromol PE/L increased the steady-state
      intracellular pH (pHi) by 0.16 +/- 0.03 pH units, as well as increasing the
      phosphorylation of ERK. The response of NHE1 to PE in CCL39 cells was determined
      by the use of specific antagonists. Use of 2 specific chemical inhibitors of
      phosphoinositide-specific phospholipase C (PLC) reduced the ability of PE to
      activate either the exchanger or ERK. Studies were conducted in PLCbeta-deficient
      cell lines derived from parental CCL39 cells. NHE1 activity in both mutant cell
      lines was increased in response to phorbal esters or lysophosphatidic acid,
      whereas the addition of PE only caused a minimal change in either pHi or ERK
      phosphorylation. These results, combined with reconstitution experiments with
      exogenously expressed PLCbeta1, PLCbeta2, or PLCbeta3, revealed that stimulation
      of NHE1 activity by PE in CCL39 cells is a PLCbeta1-coupled event. Furthermore,
      the data indicate that alpha1-adrenergic signaling of PLCbeta is upstream of ERK
      activation. These data demonstrate that PLCbeta1 is primarily involved in the
      activation of NHE1 in CCL39 fibroblasts.

PMID- 15864322
TI  - Removal of the nitro and phenyl groups from NPPB decreases its inhibitory effect
      on cytoplasmic streaming in the alga Nitella hookeri.
AB  - Structural analogues of the arylaminobenzoate 5-nitro-2-(3-phenylpropylamino)
      benzoic acid (NPPB), prepared using a simple reductive amination sequence, were
      tested for their effects on cytoplasmic streaming rates in the alga Nitella
      hookeri. Cytoplasmic streaming was sensitive to NPPB, with an IC50 value of 24
      micromol/L. Removal of the nitro group from the benzoate ring decreased the IC50
      to 455 micromol/L. The introduction of an extra carbon or double bond into the
      aliphatic chain had no effect on activity. Loss of the phenyl group decreased
      potency, with an IC50 of 6.4 mmol/L. These data are the first documenting the
      relative inhibitory effects of structural changes to arylaminobenzoates in algae.
      Patch-clamp data and the effects of tetrapentyl ammonium chloride on streaming
      suggest that the nitro and phenyl groups may act by inhibiting both K+ and Cl-
      channels. This is likely, through changes in the membrane potential, to affect
      Ca2+ fluxes and action potentials, thereby slowing cytoplasmic streaming.

PMID- 15864323
TI  - The role of detergent in refolding of GdnHCl-denatured arginine kinase from
      shrimp Fenneropenaeus Chinensis: the solubilization of aggregate and refolding in
      detergent solutions.
AB  - Strong aggregation occurred in the refolding route of arginine kinase (AK)
      denatured with 3 mol GdnHCl/L (GdnHCl, guanidine hydrochloride). The activity
      recovery of GdnHCl-denatured AK was very low and dependent on the protein
      concentration in the process of refolding. For denatured AK at 1.2 micromol/L
      concentration, the recovered activity yield was about 45.2% of the native enzyme,
      whereas at 5.2 micromol/L the activity recovery yield was only 20% of native
      activity. The nonionic detergent Triton X-100 and Tween 20 (< or = 100 mmol/L
      concentration) not only effectively blocked the aggregation but also enabled the
      denatured AK to recover most of its native activity. The kinetics of aggregate
      solubilization showed that there was an induction phase dependent on the
      detergent, but there was no dependency when detergent was absent. The apparent
      activity recovery had a cooperative relation with detergents in the process of
      refolding, which suggested the existence of some interaction between the
      detergent and the refolding intermediate. On the basis of the study results, a
      scheme of refolding was proposed.

PMID- 15864324
TI  - Optimal conditions and specific characteristics of Vent exo- DNA polymerase in
      ligation-mediated polymerase chain reaction protocols.
AB  - An optimized procedure for the ligation-mediated polymerase chain reaction (PCR)
      technique using Thermococcus litoralis exo- DNA polymerase (Vent exo-) was
      developed. The optimal dosage of Vent exo- at the primer extension and PCR
      amplification steps as well as the optimal DNA quantity to use were established.
      We showed that Vent exo- can efficiently create the blunt-ended termini required
      for subsequent linker ligation. Vent exo- proves to be more efficient than
      Pyrococcus furiosus exo- (Pfu exo-) for this task. Vent exo- resolves highly GC
      rich sequence substantially better than Thermus aquaticus DNA polymerase (Taq)
      and with a similar efficiency as Pfu exo-. The DNA/DNA polymerase activity ratio
      is significantly higher for Vent exo- than for Pfu exo-, which is reflected by
      the sensibility of Vent exo- in efficiently amplifying genomic DNA. Furthermore,
      the range of efficiency of Vent exo- demonstrates the importance of conducting
      evaluative testing to identify the optimal dosage of use of this polymerase to
      obtain successful PCR amplification. Optimal MgSO4 concentrations to use with
      Vent exo- were established. Our results show that Vent exo- DNA polymerase
      produces bands of uniform and strong intensity and can efficiently be used for
      the analysis of DNA in living cells by ligation-mediated PCR.

PMID- 15864325
TI  - Involvement of active oxygen species in protein and oligonucleotide degradation
      induced by nitrofurans.
AB  - It is of great interest to know how nitrofurans are mutagenic and clastogenic. In
      particular, the 3-amino-2-oxazolidone (AOZ) ring, deriving from a cleavage of
      furazolidone, is not further metabolized and has been found to be part of protein
      bound residues in edible tissues of farm animals and these might be released in
      the stomach of the consumer. The data in this paper show that isoniazide as well
      as AOZ and 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ), the latter deriving
      from furaltadone, cause irreversible damage to the prosthetic group of enzymes as
      well as degrade their polypeptide chain and cause fragmentation of the backbone
      chain of cellular or isolated DNA and RNA. Cellular DNA was degraded into small
      fragments of 2000 Mb, while rRNA was completely destroyed. Nitrofuran derivatives
      and hydrazides, in fact, share an N-N moiety, which is assumed to play an
      essential role in the irreversible damage observed. The key to the molecular
      mechanisms by which these compounds cause their irreversible effects may lie in
      oxygen consumption and electron spin resonance measurements, which reveal that
      both nitrofurans and isoniazide produce oxygen radicals at various degrees of
      efficiency. AOZ and AMOZ are not metabolized into more reactive metabolites,
      being themselves able to react with atmospheric oxygen and induce protein and
      oligonucleotide damage. The reaction does not require metal ions, although their
      presence will accelerate it.

PMID- 15864326
TI  - Antioxidant status in J774A.1 macrophage cell line during chronic exposure to
      glycated serum.
AB  - Advanced glycation end-products (AGEs) are linked to aging and correlated
      diseases. The aim of present study was to evaluate oxidative stress related
      parameters in J774A.1 murine macrophage cells during chronic exposure to a
      subtoxic concentration of AGE (5% ribose-glycated serum (GS)) and subsequently
      for 48 h to a higher dose (10% GS). No effects on cell viability were evident in
      either experimental condition. During chronic treatment, glycative markers (free
      and bound pentosidine) increased significantly in intra- and extracellular
      environments, but the production and release of thiobarbituric acid reactive
      substances (TBARs), as an index of lipid peroxidation, underwent a time-dependent
      decrease. Exposure to 10% GS evidenced that glycative markers rose further, while
      TBARs elicited a cellular defence against oxidative stress. Nonadapted cultures
      showed an accumulation of AGEs, a marked oxidative stress, and a loss of
      viability. During 10% GS exposure, reduced glutathione levels in adapted cultures
      remained constant, as did the oxidized glutathione to reduced glutathione ratio,
      while nonadapted cells showed a markedly increased redox ratio. A constant
      increase of heat shock protein 70 (HSP70) mRNA was observed in all experimental
      conditions. On the contrary, HSP70 expression became undetectable for a longer
      exposure time; this could be due to the direct involvement of HSP70 in the
      refolding of damaged proteins. Our findings suggest an adaptive response of
      macrophages to subtoxic doses of AGE, which could constitute an important factor
      in the spread of damage to other cellular types during aging.

PMID- 15864327
TI  - Biochemical characterization of the human placental transcription factor GCMa/1.
AB  - Glial cells missing (GCM) proteins are a novel family of zinc-containing
      transcription factors. Human GCMa/1 is primarily expressed in placental
      trophoblast cells and regulates SYNCYTIN gene expression, which mediates fusion
      of cytotrophoblasts to form the syncytiotrophoblast layer of the human placenta.
      To biochemically characterize the transcriptional activity of GCMa/1, we set up
      an in vitro transcription system for human GCMa/1 (hGCMa/1). Using G-free
      reporter constructs carrying multiple copies of wild-type or mutant GCMa-binding
      site (GBS) in front of a synthetic TATA box, we observed specific transcriptional
      activities of recombinant hGCMa/1 proteins prepared from a baculovirus--insect
      cell or Escherichia coli expression system. We further characterized GCMa/1
      mediated transcriptional activation on the native syncytin promoter. Using G-free
      reporter constructs containing the native syncytin promoter, a TATA box
      downstream of the proximal GBS in the syncytin promoter was shown to be essential
      for the transcription activation directed by hGCMa/1. Therefore, our results
      demonstrate positive transcriptional activities of GCMa/1 in vitro and provide a
      better understanding of GCMa/1-mediated SYNCYTIN gene expression.

PMID- 15864328
TI  - Differential effects of selenite and selenate on human melanocytes,
      keratinocytes, and melanoma cells.
AB  - Among the substances that attracted the attention of oncologists in recent years
      are selenium-containing compounds, both inorganic and organic. Several
      epidemiological studies have shown an inverse correlation between selenium intake
      and cancer incidence. In the experiments reported here, we compared the effects
      of 2 inorganic selenium-containing salts that differed in the level of selenium
      oxidation, selenite IV and selenate VI. We tested the effects of these 2
      compounds on cell survival and growth, cell cycle processing, cell morphology,
      cytoskeleton, and lipid peroxidation in 3 human skin cell types: normal
      keratinocytes, melanocytes, and human melanoma cell line HTB140. The different
      effects of selenite and selenate on the viability, growth, and morphology of
      normal cells and tumor cells are reported and provide a base for future research
      and treatment of some neoplastic diseases. The attention is paid to cell
      apoptosis induced by selenite and not by selenate, and the effects of tested
      substances on thioredoxin reductase system are postulated.

PMID- 15864329
TI  - Phaseococcin, an antifungal protein with antiproliferative and anti-HIV-1 reverse
      transcriptase activities from small scarlet runner beans.
AB  - From the seeds of small scarlet runner beans (Phaseolus coccineus 'Minor'), an
      antifungal protein with an N-terminal sequence homologous to those of defensins
      was isolated. The antifungal protein bound to Affi-gel blue gel and Mono S but it
      did not bind to DEAE-cellulose. It was further purified by gel filtration on a
      Superdex peptide column. It exhibited a molecular mass of 5422 Da as determined
      by mass spectrometry. The protein, designated as phaseococcin, suppressed
      mycelial growth in a number of fungi including Botrytis cinerea, Coprinus
      comatus, Fusarium oxysporum, Mycosphaerella arachidicola, Physalospora piricola,
      and Rhizoctonia solani. It also inhibited proliferation in several Bacillus
      species and the leukemia cell lines HL60 and L1210 and curtailed the activity of
      HIV-1 reverse transcriptase. It did not affect proliferation of mouse splenocytes
      and neither did it inhibit protein synthesis in a cell-free rabbit reticulocyte
      lysate system.

PMID- 15864330
TI  - Zinc-sensitive genes as potential new target genes of the metal transcription
      factor-1 (MTF-1).
AB  - Zinc is an essential trace element that serves as a structural constituent of a
      large number of transcription factors, which explains its pivotal role in the
      control of gene expression. Previous studies investigating the effect of zinc
      deficiency and zinc supplementation on gene expression in the human
      adenocarcinoma cell line HT-29 led to the identification of a considerable number
      of genes responding to alterations in cellular zinc status with changes in steady
      state mRNA levels. For 9 of 20 genes from these previous screenings that were
      studied in more detail, mRNA steady state levels responded to both high and low
      media zinc concentrations. As they are primarily zinc-dependent, we assessed
      whether these genes are controlled by the zinc-finger metal transcription factor
      MTF-1. To test this hypothesis we generated a doxycyline-inducible Tet-On HT-29
      cell line overexpressing MTF-1. Using this conditional expression system, we
      present evidence that Kruppel-like factor 4 (klf4), hepatitis A virus cellular
      receptor 1 (hhav), and complement factor B (cfbp) are 3 potential new target
      genes of MTF-1. To support this, we used in silico analysis to screen for metal
      responsive elements (MREs) within promotors of zinc-sensitive genes. We conclude
      that zinc responsiveness of klf4, hhav, and cfbp in HT-29 cells is mediated at
      least in part by MTF-1.

PMID- 15864331
TI  - Targeted modification of the complete chicken lysozyme gene by poxvirus-mediated
      recombination.
AB  - We have developed a novel ex vivo system for the rapid one-step targeted
      modification of large eucaryotic DNA sequences. The highly recombinant
      environment resulting from infection of rabbit cornea cells with the Shope
      fibroma virus was exploited to mediate precise modifications of the complete
      chicken lysozyme gene domain (21.5 kb). Homologous recombination was designed to
      occur between target DNA (containing the complete lysozyme gene domain)
      maintained in a lambda bacteriophage vector and modified targeting DNA maintained
      in a plasmid. The targeting plasmids were designed to transfer exogenous
      sequences (for example, beta-galactosidase alpha-complement, green fluorescent
      protein, and hydrophobic tail coding sequences) to specific sites within the
      lysozyme gene domain. Cotransfection of the target phage and a targeting plasmid
      into Shope fibroma virus infected cells resulted in the poxvirus-mediated
      transfer of the modified sequences from plasmid to phage. Phage DNA (recombinant
      and nonrecombinant) was then harvested from the total cellular DNA by packaging
      into lambda phage particles and correct recombinants were identified. Four
      different gene-targeting pairings were carried out, and from 3% to 11% of the
      recovered phages were recombinant. Using this poxvirus-mediated targeting system,
      four different regions of the chicken lysozyme gene domain have been modified
      precisely by our research group overall with a variety of inserts (6-971 bp),
      deletions (584-3000 bp), and replacements. We have never failed to obtain the
      desired recombinant. Poxvirus-mediated recombination thus constitutes a routine,
      rapid, and remarkably efficient genetic engineering system for the precise
      modification of large eucaryotic gene domains when compared with traditional
      practices.

PMID- 15864332
TI  - Constitutive expression of human lactoferrin and its N-lobe in rice plants to
      confer disease resistance.
AB  - The milk protein, lactoferrin, is known to have antibacterial, antiviral, and
      antifungal activities. To explore the possibility of conferring disease
      resistance in plants by expressing this protein, the gene for the full-length
      human lactoferrin (HLF), as well as the N-lobe, the N-terminal half molecule
      (HLFN), was introduced into rice plants and expressed constitutively under the
      control of the cauliflower mosaic virus 35S promotor. Western blot analysis of
      leaves from HLF-transgenic rice plants showed an 80 kDa-band, which was about 1-2
      kDa less than human milk lactoferrin. HLFN was expressed as a 45-kDa protein and
      retained its heparin-binding property. Deglycosylation experiments suggested that
      both proteins produced by the plants had plant-type oligosaccharide chains. The
      transgenic rice plants were assessed for resistance against disease-causing
      bacteria, virus, and fungi. Of the pathogens tested, significant resistance
      against Burkholderia (Pseudomonas) plantarii, the causative agent of bacterial
      seedling blight disease, was observed in the transgenic plants expressing HLF or
      HLFN.

PMID- 15864333
TI  - Raising consciousness.
AB  - The national debate over Terri Schiavo exposed a critical gap between emotional
      fervor about brain-injured patients and the medical science that informs
      standards of care for them. Some of the questions raised in the public and legal
      forums point to a need for research and enhanced understanding of the mechanisms
      of recovery from disorders of consciousness.

PMID- 15864334
TI  - Vaccine program rubs out rubella in the US.

PMID- 15864335
TI  - Belgian scientists awarded top honors.

PMID- 15864336
TI  - In the debate of sex and science, Summers, Hopkins, and the X chromosome battle
      it out.

PMID- 15864337
TI  - PETA continues to claw at Columbia scientists.

PMID- 15864338
TI  - Inflammation, stress, and diabetes.
AB  - Over the last decade, an abundance of evidence has emerged demonstrating a close
      link between metabolism and immunity. It is now clear that obesity is associated
      with a state of chronic low-level inflammation. In this article, we discuss the
      molecular and cellular underpinnings of obesity-induced inflammation and the
      signaling pathways at the intersection of metabolism and inflammation that
      contribute to diabetes. We also consider mechanisms through which the
      inflammatory response may be initiated and discuss the reasons for the
      inflammatory response in obesity. We put forth for consideration some hypotheses
      regarding important unanswered questions in the field and suggest a model for the
      integration of inflammatory and metabolic pathways in metabolic disease.

PMID- 15864339
TI  - The role of cerebral amyloid beta accumulation in common forms of Alzheimer
      disease.
AB  - For approximately 80 years following Alzheimer's description of the disease that
      bears his name, a gulf divided researchers who believed that extracellular
      deposits of the amyloid beta (Abeta) peptide were pathogenic from those who
      believed that the deposits were secondary detritus. Since 1990, the discoveries
      of missense mutations in the Abeta peptide precursor (APP) and the APP-cleaving
      enzyme presenilin 1 (PS1) have enabled much progress in understanding the
      molecular, cellular, and tissue pathology of the aggregates that accumulate in
      the interstices of the brains of patients with autosomal dominant familial
      Alzheimer disease (AD). Clarification of the molecular basis of common forms of
      AD has been more elusive. The central questions in common AD focus on whether
      cerebral and cerebrovascular Abeta accumulation is (a) a final neurotoxic
      pathway, common to all forms of AD; (b) a toxic by-product of an independent
      primary metabolic lesion that, by itself, is also neurotoxic; or (c) an inert by
      product of an independent primary neurotoxic reaction. Antiamyloid medications
      are entering clinical trials so that researchers can evaluate whether abolition
      of cerebral amyloidosis can mitigate, treat, or prevent the dementia associated
      with common forms of AD. Successful development of antiamyloid medications is
      critical for elucidating the role of Abeta in common AD.

PMID- 15864340
TI  - Food for thought: endocannabinoid modulation of lipogenesis.
AB  - An emerging body of evidence implicates peripheral and central endocannabinoid
      pathways in the regulation of feeding behavior and body weight. A report in this
      issue of the JCI demonstrates the presence of a common endocannabinoid-regulated
      molecular pathway for peripheral lipogenic and central appetitive regulation.
      This pathway involves the activation of the transcription factor SREBP-1c and its
      associated enzymes, acetyl-CoA carboxylase-1 and fatty acid synthase, in the
      liver and hypothalamus. Activation of cannabinoid receptor 1 (CB(1)) in liver
      plays a key role in increased serum lipid production, fatty liver, and possibly
      diet-induced obesity. Conversely, stimulation of these receptors in the
      hypothalamus may lead to an increase in food consumption. Thus, targeting both of
      these pathways with CB(1) antagonists could promote sustained weight loss and
      favorable serum lipid profiles in obese patients.

PMID- 15864341
TI  - Chemokine-mediated angiogenesis: an essential link in the evolution of airway
      fibrosis?
AB  - Angiogenesis may be an important factor in the development of fibrotic lung
      disease. Prior studies have strongly suggested a role for angiogenic vascular
      remodeling in pulmonary fibrosis, and emerging evidence indicates that new vessel
      formation is critical in airway fibrosis. Bronchiolitis obliterans syndrome is a
      fibrotic occlusion of distal airways that is largely responsible for the
      morbidity and mortality of patients after lung transplantation. In this issue,
      Belperio et al. demonstrate a role for CXC chemokine receptor 2 in the regulation
      of angiogenesis-mediated airway fibroproliferation. By integrating an
      understanding of neovascularization into the study of events that occur between
      inflammation and fibrosis, it becomes increasingly possible to rationally design
      therapies that can halt conditions of maladaptive fibrosis.

PMID- 15864342
TI  - The role of hepatic insulin receptors in the regulation of glucose production.
AB  - The inability of insulin to suppress hepatic glucose production (HGP) is a key
      defect found in type 2 diabetes. Insulin inhibits HGP through both direct and
      indirect means, the latter of which include inhibition of glucagon secretion,
      reduction in plasma nonesterified fatty acid level, decrease in the load of
      gluconeogenic substrates reaching the liver, and change in neural signaling to
      the liver. Two studies in this issue of the JCI demonstrate that selective
      changes in the expression of insulin receptors in mouse liver do not have a
      detectable effect on the ability of insulin to inhibit HGP (see the related
      articles beginning on pages 1306 and 1314). These provocative data suggest that
      the indirect effects of insulin on the liver are the primary determinant of HGP
      in mice.

PMID- 15864343
TI  - Contribution of adipose tissue and de novo lipogenesis to nonalcoholic fatty
      liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a component of the metabolic
      syndrome, with a clinical spectrum ranging from simple fatty liver to
      steatohepatitis, cirrhosis, and hepatocellular carcinoma. The primary event of
      NAFLD is the accumulation of triacylglycerols (TAGs) in hepatocytes. In this
      issue of the JCI, Donnelly et al. report on their use of stable isotope
      methodology to show that fatty acids stored in adipose tissue and fatty acids
      newly made within the liver through de novo lipogenesis are the major sources of
      TAGs in the liver and are secreted as lipoproteins in NAFLD.

PMID- 15864344
TI  - Caffey disease: an unlikely collagenopathy.
AB  - Infantile cortical hyperostosis (also known as Caffey disease) is characterized
      by hyperirritability, acute inflammation of soft tissues, and profound
      alterations of the shape and structure of the underlying bones, particularly the
      long bones, mandible, clavicles, or ribs. In this issue of the JCI, Gensure et
      al. undertook fine mapping of the genetic locus for this disease in a large
      kindred of individuals with the autosomal dominant form of the condition. The
      authors found a novel missense mutation in COL1A1, the gene encoding the alpha1
      chain of type I collagen, in all affected individuals in 3 discrete pedigrees.
      This is a surprising finding, as all other reported mutations affecting the
      synthesis of type I collagen lead to conditions such as osteogenesis imperfecta
      and Ehlers-Danlos syndrome, in which quantitative or qualitative defects in type
      I collagen synthesis give rise to bone fragility and/or connective tissue
      hyperextensibility. The deleterious effect of the mutation on collagen fibril
      morphology is demonstrated; however, the precise functional link between the
      reported missense mutation and the localized inflammation and hyperostosis seen
      in Caffey disease awaits future studies.

PMID- 15864345
TI  - A tax on luxury: HTLV-I infection of CD4+CD25+ Tregs.
AB  - Almost a quarter of a century ago, Oldstone and colleagues proposed that
      infection of cells by noncytopathic viruses may lead to an alteration of the
      cells' ability to produce certain products or perform certain tasks, i.e.,
      inhibition of "luxury function." In this issue of the JCI, this topic has been
      revisited by Yamano et al., who demonstrate that human T cell lymphotropic virus
      type I (HTLV-I) infection of CD4(+)CD25(+) Tregs in patients with HTLV-I
      associated myelopathy/tropical spastic paraparesis (HAM/TSP) results in a
      decrease in FOXP3 mRNA and protein expression. This leads to the inability of
      HTLV-I-infected CD4(+)CD25(+) Tregs to inhibit the proliferation of CD4(+)CD25(-)
      Tregs, due to the effect of the HTLV-I tax gene. Defects in the Treg population
      could be responsible for the large numbers of virus-specific T cells and
      occurrence of lymphoproliferation and inflammatory autoimmune disease in HAM/TSP
      patients.

PMID- 15864346
TI  - A seek-and-hide game between Cd1-restricted T cells and herpesviruses.
AB  - T and NK cells collaborate to control viral infections, discerning minute
      differences between infected and uninfected cells. At the same time, viruses have
      evolved to escape this discovery. In this issue of the JCI, Ganem and colleagues
      show that Kaposi sarcoma-associated herpesvirus (KSHV) inhibits CD1d presentation
      to T cells. This novel immune evasion strategy highlights the importance of CD1d
      restricted T cells in controlling viral infection and raises an interesting
      question: how do T cells recognize viruses in the context of CD1 molecules that
      bind lipids? In the case of herpesviruses, alterations in endosomal trafficking
      might trigger redistribution of CD1/lipid complexes to cell surfaces, thereby
      promoting recognition by CD1d-restricted T cells.

PMID- 15864347
TI  - Role of CXCR2/CXCR2 ligands in vascular remodeling during bronchiolitis
      obliterans syndrome.
AB  - Angiogenesis and vascular remodeling support fibroproliferative processes;
      however, no study has addressed the importance of angiogenesis during fibro
      obliteration of the allograft airway during bronchiolitis obliterans syndrome
      (BOS) that occurs after lung transplantation. The ELR(+) CXC chemokines both
      mediate neutrophil recruitment and promote angiogenesis. Their shared endothelial
      cell receptor is the G-coupled protein receptor CXC chemokine receptor 2 (CXCR2).
      We found that elevated levels of multiple ELR(+) CXC chemokines correlated with
      the presence of BOS. Proof-of-concept studies using a murine model of BOS not
      only demonstrated an early neutrophil infiltration but also marked vascular
      remodeling in the tracheal allografts. In addition, tracheal allograft ELR(+) CXC
      chemokines were persistently expressed even in the absence of significant
      neutrophil infiltration and were temporally associated with vascular remodeling
      during fibro-obliteration of the tracheal allograft. Furthermore, in neutralizing
      studies, treatment with anti-CXCR2 Abs inhibited early neutrophil infiltration
      and later vascular remodeling, which resulted in the attenuation of murine BOS. A
      more profound attenuation of fibro-obliteration was seen when CXCR2(-/-) mice
      received cyclosporin A. This supports the notion that the CXCR2/CXCR2 ligand
      biological axis has a bimodal function during the course of BOS: early, it is
      important for neutrophil recruitment and later, during fibro-obliteration, it is
      important for vascular remodeling independent of neutrophil recruitment.

PMID- 15864348
TI  - A novel COL1A1 mutation in infantile cortical hyperostosis (Caffey disease)
      expands the spectrum of collagen-related disorders.
AB  - Infantile cortical hyperostosis (Caffey disease) is characterized by spontaneous
      episodes of subperiosteal new bone formation along 1 or more bones commencing
      within the first 5 months of life. A genome-wide screen for genetic linkage in a
      large family with an autosomal dominant form of Caffey disease (ADC) revealed a
      locus on chromosome 17q21 (LOD score, 6.78). Affected individuals and obligate
      carriers were heterozygous for a missense mutation (3040Ctwo head right arrowT)
      in exon 41 of the gene encoding the alpha1(I) chain of type I collagen (COL1A1),
      altering residue 836 (R836C) in the triple-helical domain of this chain. The same
      mutation was identified in affected members of 2 unrelated, smaller families with
      ADC, but not in 2 prenatal cases and not in more than 300 chromosomes from
      healthy individuals. Fibroblast cultures from an affected individual produced
      abnormal disulfide-bonded dimeric alpha1(I) chains. Dermal collagen fibrils of
      the same individual were larger, more variable in shape and size, and less
      densely packed than those in control samples. Individuals bearing the mutation,
      whether they had experienced an episode of cortical hyperostosis or not, had
      joint hyperlaxity, hyperextensible skin, and inguinal hernias resembling symptoms
      of a mild form of Ehlers-Danlos syndrome type III. These findings extend the
      spectrum of COL1A1-related diseases to include a hyperostotic disorder.

PMID- 15864349
TI  - Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid
      synthesis and contributes to diet-induced obesity.
AB  - Endogenous cannabinoids acting at CB(1) receptors stimulate appetite, and CB(1)
      antagonists show promise in the treatment of obesity. CB(1) (-/-) mice are
      resistant to diet-induced obesity even though their caloric intake is similar to
      that of wild-type mice, suggesting that endocannabinoids also regulate fat
      metabolism. Here, we investigated the possible role of endocannabinoids in the
      regulation of hepatic lipogenesis. Activation of CB(1) in mice increases the
      hepatic gene expression of the lipogenic transcription factor SREBP-1c and its
      targets acetyl-CoA carboxylase-1 and fatty acid synthase (FAS). Treatment with a
      CB(1) agonist also increases de novo fatty acid synthesis in the liver or in
      isolated hepatocytes, which express CB(1). High-fat diet increases hepatic levels
      of the endocannabinoid anandamide (arachidonoyl ethanolamide), CB(1) density, and
      basal rates of fatty acid synthesis, and the latter is reduced by CB(1) blockade.
      In the hypothalamus, where FAS inhibitors elicit anorexia, SREBP-1c and FAS
      expression are similarly affected by CB(1) ligands. We conclude that anandamide
      acting at hepatic CB(1) contributes to diet-induced obesity and that the FAS
      pathway may be a common molecular target for central appetitive and peripheral
      metabolic regulation.

PMID- 15864350
TI  - Severe impairment in liver insulin signaling fails to alter hepatic insulin
      action in conscious mice.
AB  - Insulin exerts its potent effects on hepatic glucose fluxes via direct and
      indirect mechanisms. Whereas a liver-specific insulin receptor (IR) knockout
      (LIRKO) mouse exhibits glucose intolerance as well as insulin resistance, it is
      unclear whether a more acute decrease in the expression of hepatic IR would be
      sufficient to induce hepatic insulin resistance. Here we report that the
      downregulation of hepatic IR expression by up to 95% does not modify hepatic
      insulin action. The i.p. administration (2 injections over 1 week) of an
      antisense oligodeoxynucleotide (ASO) directed to reduce insulin expression
      downregulated hepatic IR expression in C57BL6J mice. A high dose of IR-ASO
      decreased IR protein approximately 95%, while a control-ASO failed to modify IR
      expression. At this dose, the IR-ASO also decreased IR expression in adipose
      tissue but did not significantly decrease IR expression in hypothalamus or
      skeletal muscle. Insulin action was assessed with insulin clamp studies in
      conscious mice. The rate of glucose infusion during the clamp studies was
      comparable in control-ASO- and IR-ASO-treated mice. Importantly, the depletion of
      liver IR protein markedly impaired downstream insulin signaling in the liver, but
      it failed to modify the rate of glucose production. Thus, near ablation of liver
      IR does not alter insulin action on glucose production.

PMID- 15864351
TI  - Restoration of liver insulin signaling in Insr knockout mice fails to normalize
      hepatic insulin action.
AB  - Partial restoration of insulin receptor Insr expression in brain, liver, and
      pancreatic beta cells is sufficient for rescuing Insr knockout mice from neonatal
      death, preventing diabetes ketoacidosis, and normalizing life span and
      reproductive function. However, the transgenically rescued mice (referred to as
      L1) have marked hyperinsulinemia, and approximately 30% develop late-onset type 2
      diabetes. Analyses of protein expression indicated that L1 mice had modestly
      reduced Insr content but normal insulin-stimulated Akt phosphorylation in the
      liver. Conversely, L1 mice had a near complete ablation of Insr protein product
      in the arcuate and paraventricular nuclei of the hypothalamus, which was
      associated with a failure to undergo insulin-dependent Akt phosphorylation in the
      hypothalamus. To test whether reconstitution of insulin signaling in the liver is
      sufficient for restoring in vivo hepatic insulin action, we performed euglycemic
      hyperinsulinemic clamp studies in conscious L1 and WT mice. During the clamp, L1
      mice required an approximately 50% lower rate of glucose infusion than did WT
      controls, while the rate of glucose disappearance was not significantly altered.
      Conversely, the rate of glucose production was increased approximately 2-fold in
      L1 mice. Thus, restoration of hepatic insulin signaling in Insr knockout mice
      fails to normalize the in vivo response to insulin.

PMID- 15864352
TI  - Sources of fatty acids stored in liver and secreted via lipoproteins in patients
      with nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of
      excess liver triacylglycerol (TAG), inflammation, and liver damage. The goal of
      the present study was to directly quantify the biological sources of hepatic and
      plasma lipoprotein TAG in NAFLD. Patients (5 male and 4 female; 44 +/- 10 years
      of age) scheduled for a medically indicated liver biopsy were infused with and
      orally fed stable isotopes for 4 days to label and track serum nonesterified
      fatty acids (NEFAs), dietary fatty acids, and those derived from the de novo
      lipogenesis (DNL) pathway, present in liver tissue and lipoprotein TAG. Hepatic
      and lipoprotein TAG fatty acids were analyzed by gas chromatography/mass
      spectrometry. NAFLD patients were obese, with fasting hypertriglyceridemia and
      hyperinsulinemia. Of the TAG accounted for in liver, 59.0% +/- 9.9% of TAG arose
      from NEFAs; 26.1% +/- 6.7%, from DNL; and 14.9% +/- 7.0%, from the diet. The
      pattern of labeling in VLDL was similar to that in liver, and throughout the 4
      days of labeling, the liver demonstrated reciprocal use of adipose and dietary
      fatty acids. DNL was elevated in the fasting state and demonstrated no diurnal
      variation. These quantitative metabolic data document that both elevated
      peripheral fatty acids and DNL contribute to the accumulation of hepatic and
      lipoprotein fat in NAFLD.

PMID- 15864353
TI  - Virus-induced dysfunction of CD4+CD25+ T cells in patients with HTLV-I-associated
      neuroimmunological disease.
AB  - CD4(+)CD25(+) Tregs are important in the maintenance of immunological self
      tolerance and in the prevention of autoimmune diseases. As the CD4(+)CD25(+) T
      cell population in patients with human T cell lymphotropic virus type I
      associated (HTLV-I-associated) myelopathy/tropical spastic paraparesis (HAM/TSP)
      has been shown to be a major reservoir for this virus, it was of interest to
      determine whether the frequency and function of CD4(+)CD25(+) Tregs in HAM/TSP
      patients might be affected. In these cells, both mRNA and protein expression of
      the forkhead transcription factor Foxp3, a specific marker of Tregs, were lower
      than those in CD4(+)CD25(+) T cells from healthy individuals. The virus-encoded
      transactivating HTLV-I tax gene was demonstrated to have a direct inhibitory
      effect on Foxp3 expression and function of CD4(+)CD25(+) T cells. This is the
      first report to our knowledge demonstrating the role of a specific viral gene
      product (HTLV-I Tax) on the expression of genes associated with Tregs (in
      particular, foxp3) resulting in inhibition of Treg function. These results
      suggest that direct human retroviral infection of CD4(+)CD25(+) T cells may be
      associated with the pathogenesis of HTLV-I-associated neurologic disease.

PMID- 15864355
TI  - The influence of age on reproductive performance of the predatory ladybird
      beetle, Propylea dissecta.
AB  - The influence of age on reproductive performance of an aphidophagous ladybird
      beetle, Propylea dissecta was examined using male and female beetles of varying
      ages (1-30 days) after a single mating stimulus. All the intermediate (10 to 20
      days old) and old (30 days old) age females mated with all intermediate and old
      age males, while only a fraction (0.29%) of younger females, 1 to 5 days old,
      mated with males of similar or older age. The willingness to mate was male age
      dependent. It increased sigmoidally with increase in adult age. Adult males were
      more willing to mate with females irrespective of age. Mating duration was
      longest amongst older adults (30 day-old males and 20 day-old females). Male age
      did not contribute to shaping the fecundity of the female ladybird. Fecundity was
      female age dependent and it increased with age up to 20 days and thereafter
      decreased. 20 day-old females were most fecund producing 867 eggs after a single
      mating. Progeny production was male age dependent and eggs sired by 20-30 day-old
      males had significantly higher viability than those sired by younger males.
      Prolonged mating increased fecundity and egg viability. The results reveal that
      males of intermediate age were better mates. This information may improve our
      understanding of the effect of aging on reproduction in ladybirds and may help
      mass-multiplication of the ladybird beetles using adults of optimal age.

PMID- 15864354
TI  - Regulation of CD1d expression and function by a herpesvirus infection.
AB  - Little is known about the role of CD1d-restricted T cells in antiviral immune
      responses. Here we show that the lytic replication cycle of the Kaposi sarcoma
      associated herpesvirus (KSHV) promotes downregulation of cell-surface CD1d. This
      is caused by expression of the 2 modulator of immune recognition (MIR) proteins
      of the virus, each of which promotes the loss of surface CD1d expression
      following transfection into uninfected cells. Inhibition of CD1d surface
      expression is due to ubiquitination of the CD1d alpha-chain on a unique lysine
      residue in its cytoplasmic tail, which triggers endocytosis. Unlike MIR-mediated
      MHC class I downregulation, however, CD1d downregulation does not appear to
      include accelerated lysosomal degradation. MIR2-induced downregulation of CD1d
      results in reduced activation of CD1d-restricted T cells in vitro. KSHV
      modulation of CD1d expression represents a strategy for viral evasion of innate
      host immune responses and implicates CD1d-restricted T cells as regulators of
      this viral infection.

PMID- 15864356
TI  - Anti-anxiety Activity Studies on Homoeopathic Formulations of Turnera
      aphrodisiaca Ward.
AB  - Turnera aphrodisiaca Ward (Turneraceae) has been traditionally used for the
      treatment of anxiety neurosis, and as an aphrodisiac. Mother tinctures (85%
      ethanol extracts) of T. aphrodisiaca have also been used for the treatment of
      central nervous system disorders. In the present investigation, T. aphrodisiaca
      mother tinctures formulated by three reputed manufacturers of homoeopathic
      medicines (NLK, DWSG and SBL) were evaluated for their anxiolytic activity. Dried
      mother tinctures of T. aphrodisiaca were subjected to anxiolytic activity
      evaluation at various doses, i.e. 50, 75, 100, 125 or 150 mg/kg p.o. in mice
      using elevated plus maze apparatus. Dried mother tinctures exhibited significant
      anxiolytic activity at 50 mg/kg (NLK), 75 mg/kg (DWSG) and 125 mg/kg (SBL),
      respectively, with reference to control as well as standard (diazepam, 2 mg/kg
      p.o.). Mother tinctures of T. aphrodisiaca available in the market, have
      significant anxiolytic activity. Amongst the three mother tinctures of T.
      aphrodisiaca analyzed, the dry residue of NLK possesses the highest amount of
      anxiolytic constituent(s). To ensure uniformity and consistency of biological
      effects in herbal formulations, these should be standardized on the basis of
      bioactive markers. The authors are actively involved in isolating the bioactive
      constituent(s) from T. aphrodisiaca so that the plant can be standardized on the
      basis of biologically active constituent(s).

PMID- 15864357
TI  - Comparative Efficacy of Pre-feeding, Post-feeding and Combined Pre- and Post
      feeding of Two Microdoses of a Potentized Homeopathic Drug, Mercurius Solubilis,
      in Ameliorating Genotoxic Effects Produced by Mercuric Chloride in Mice.
AB  - Mercury and its derivatives have become an alarming environmental problem,
      necessitating the search for effective antagonists, including homeopathic drugs,
      which are generally used in micro doses and are devoid of any palpable side
      effects. On the basis of homeopathic similia principle, two potencies of
      Mercurius solubilis (Merc Sol-30 and Merc Sol-200) were tested by three
      administrative modes, i.e. pre-feeding, post-feeding and combined pre- and post
      feeding, for their possible efficacy in ameliorating mercuric chloride-induced
      genotoxicity in mice. Healthy mice, Mus musculus, were intraperitoneally injected
      with 0.06% solution of mercuric chloride at the rate of 1 ml/100 g of body
      weight, and assessed for genotoxic effects through conventional endpoints. i.e.
      chromosome aberrations, micronuclei, mitotic index and sperm head abnormality,
      keeping suitable controls. Mercuric chloride-treated mice were divided into three
      sub-groups, which were orally administered with the drug prior to, after and both
      prior to and after injection of mercuric chloride, and their genotoxic effects
      were analysed at specific intervals of fixation. Mercuric chloride treatment
      generally produced more chromosome aberations, micronuclei and sperm head anomaly
      in mice, but the mitotic index appeared to be slightly reduced. While chromosome
      aberations, micronuclei and sperm head anomaly were generally reduced in the drug
      fed series, the mitotic index showed an apparent increase. In most cases, the
      combined pre- and post-feeding mode appeared to show the maximum amelioration,
      followed by post-feeding and pre-feeding, in that order. The amelioration by Merc
      Sol-200 appeared to be slightly more pronounced. We conclude that potentized
      homeopathic drugs can serve as possible anti-genotoxic agents against specific
      environmental mutagens, including toxic heavy metals.

PMID- 15864358
TI  - Familial cystic nephroma in two siblings with pleuropulmonary blastoma.
AB  - Cystic nephroma (CN) and pleuropulmonary blastoma (PPB) are rare tumors. In the
      cases presented here, a 13-month-old boy underwent right radical nephrectomy for
      CN. From the family history we learned that four years ago the patient's older
      sister underwent left radical nephrectomy for CN at a different center when she
      was 4 years old. A lung tumor was detected in the sister one year after
      nephrectomy. Biopsy from the lung tumor revealed PPB, and the sister died within
      one year after biopsy. To the knowledge of the authors, these cases represent the
      second reported familial occurrence of CN and the fourth of CN and PPB.

PMID- 15864359
TI  - Fast food and children and adolescents: implications for practitioners.

PMID- 15864360
TI  - Pediatric hypertension: a review for the primary care provider.

PMID- 15864361
TI  - Meeting the needs of parents and pediatric patients: results of a survey on
      primary nocturnal enuresis.
AB  - Primary nocturnal enuresis (PNE) affects about 7 million children and adolescents
      in the United States. A telephone survey of 745 parents/guardians of children
      aged 3 to 14 years was conducted to determine their knowledge and attitudes about
      PNE. Most did not know that PNE is a physical problem. Although 82% would want
      healthcare providers to discuss PNE with them if their child older than 6 years
      wet the bed, most would be uncomfortable initiating the dialogue. According to
      parents, healthcare providers either never or rarely discuss PNE. For the benefit
      of their young patients, healthcare providers must initiate discussion about PNE.

PMID- 15864362
TI  - Community physicians' attitudes toward electronic follow-up after an emergency
      department visit.
AB  - Over 1-month, a survey was faxed to family primary care practitioners (PCPs) in
      the Greater Toronto area who referred patients to the Hospital for Sick Children
      (Toronto) emergency department (ED). Information about demographics, Internet
      access, and whether PCPs were interested in receiving e-mailed information about
      their patients. Of the 323 PCPs, 24% were excluded because they could not receive
      a fax or they had an office outside the hospital's area code. One hundred fifty
      (61%) completed the survey-48% were family-physicians and 52% were pediatricians.
      Ninety-seven percent had Internet access and 9% had no personal e-mail. In total,
      61% were interested in receiving electronic communication about their patients
      visiting the ED. Pediatricians were much more interested in the information
      compared to family physicians (p<0.0005). Having an e-mail account at home and at
      work, Internet access in the office, and reading e-mail once a day (or more) were
      the strongest indicators of being interested in receiving information. The main
      reason for disinterest however, was not enough time to read the e-mails (46% of
      non-interested PCPs).

PMID- 15864363
TI  - Childhood bathtub-related injuries: slip and fall prevalence and prevention.
AB  - This study was conducted to describe the epidemiology of childhood bathtub
      related injuries and to recommend methods for prevention of bathtub-related slips
      and falls. A consecutive series of 204 children, who were treated for bathtub
      related injuries in a pediatric emergency department during a 3-year period were
      included in the study. The age range was 4 months to 16 years (mean 3.1, SD 2.8,
      median 2.8 years). Slips and falls accounted for 82.3% (168/204) of mechanisms of
      injuries. Lacerations, the most common injury type, accounted for 66.7% (136/204)
      of cases. The most frequent anatomic location of injury was the head or face
      (68.1%, 139/204). Adult supervision was present during 84.8% (67/79) of the
      injuries among children younger than 5 years. Parents changed the bathing
      environment after the patients' injury in 82.3% (65/79) of cases. Injuries due to
      slips and falls are the most common type of childhood bathtub-related injury.
      Increased supervision alone will not be sufficient to prevent these injuries,
      given that adult supervision is already present in most cases. These injuries are
      most effectively prevented by passive methods, such as providing an effective
      slip-resistant bathtub surface. The large number of bathtub-related injuries
      associated with slips and falls argues for exploring a higher coefficient of
      friction standard for bathtubs, which may lead to fewer injuries.

PMID- 15864364
TI  - Asking the correct questions to assess asthma symptoms.
AB  - A national survey of 896 parents of children with asthma was performed and
      responses to 2 types of inquiry were compared: global assessment versus specific
      assessment of symptoms. Almost all parents, 860 (96%), described their child's
      asthma as under "good control'' when asked a global assessment question. However,
      306 (34%)-when asked specific questions-actually described poor asthma control
      with frequent symptoms. Medicaid insurance (OR: 1.59; 95% CI: 1.03, 2.44) and
      parental smoking (OR: 1.60; 95% CI: 1.06, 2.43) increased the likelihood that
      parents' responses would be at risk for misinterpretation. Increased education
      (OR 0.41: 95% CI: 0.18, 0.91) and English as the primary language (OR 0.39; 95%
      CI 0.16, 0.96) were associated with decreased likelihood of misinterpretation.
      Vague, global assessment questions lead to incomplete clinical information and
      places the patient at risk for inadequate asthma therapy. A better approach is to
      use specific questions to determine the frequency of daytime or nighttime
      symptoms.

PMID- 15864365
TI  - Parental stress and maladjustment in children with short stature.
AB  - This study examined the psychometric properties of a measure of chronic disease
      related parental stress, the Pediatric Inventory for Parents (PIP), in a sample
      of 22 children with short stature. Additionally, we investigated relations among
      disease-related parental stress, parental state anxiety, and children's
      behavioral and psychological maladjustment. Results demonstrated acceptable
      internal consistency and convergent validity for the PIP. Significant and
      positive relations of medium to large effect sizes between parenting stress and
      internalizing and externalizing maladjustment were found. Recommendations for use
      of the PIP in clinical settings and future research directions are discussed.

PMID- 15864366
TI  - The incidence, treatment, and follow-up of iron deficiency in a tertiary care
      pediatric clinic.
AB  - To assess the incidence, treatment, and follow-up of iron deficiency in children
      seen in a tertiary hospital, a retrospective chart review was performed in 2002
      of 364 consecutive children screened for iron deficiency with free erythrocyte
      protoporphyrin and hemoglobin. Sixty-five of the 352 children studied (18.5%)
      were iron-deficient and 19 patients (5.4%) were anemic. Eighty percent of the
      affected children were treated with iron, and only 25% had follow-up blood
      testing done. Iron deficiency is common in children younger than 2 years of age.
      Whether or not the children had anemia, treatment and follow-up were less than
      optimal.

PMID- 15864367
TI  - Inaccuracy of stated versus measured parental heights.
AB  - Routine measurement of children's height is essential in monitoring for
      deviations in normal growth velocity. Target adult height of children is
      estimated by determining an adjusted midparental height. Such determinations are
      dependent on the accurate acquisition of parental height. Incorrect assessment of
      parental height will result in inaccurate expectations for the child's height. To
      observe the difference between stated and measured parental heights within a
      United States subspecialty setting, prospective acquisition of parental stated
      and measured heights during the summer months of 2000 and 2001 was examined. Two
      hundred and thirty-eight parents, 185 mothers and 53 fathers, were measured. The
      mean values of the stated heights for mothers and fathers were 163.7 cm +/- 6.3
      cm and 177.1 cm +/- 8.6 cm, respectively. The corresponding measured heights were
      163.0 cm +/- 5.9 cm and 175.2 cm +/- 6.6 cm, respectively. The mean height
      difference for mothers was 0.69 cm (p<0.001) while the mean height difference for
      fathers was 1.90 cm (p<0.001). Parents significantly overestimate their height in
      a clinical setting. Fathers overestimate to a greater degree than mothers. These
      findings emphasize the need to obtain height measurement of parents along with
      that of their children in assessing for linear growth delay.

PMID- 15864368
TI  - Referral by pediatricians of children with behavioral health disorders.
AB  - A standard interview guide focused on behavioral health referral practices and
      communication patterns was developed and administered to 47 pediatricians in
      private practice. Results suggested that the most frequent reasons for referral
      to a mental health provider were diagnostic uncertainty, failure to respond to
      treatment, presence of severe affective symptoms, and need for ongoing
      psychotherapy. Only a third of the providers indicated that their patients
      frequently followed through with recommendations to receive mental health care.
      More than half of the pediatricians wanted more information regarding their
      patients referred for mental health services, and they expressed a strong
      interest in colocation with a mental health provider.

PMID- 15864369
TI  - Enteric gram-negative sepsis complicating rotavirus gastroenteritis in previously
      healthy infants.

PMID- 15864370
TI  - Giant cell fibroblastoma masquerading as prepubertal gynecomastia.

PMID- 15864371
TI  - Near strangulation as a result of hair tourniquet syndrome.
AB  - Hair tourniquet syndrome has been a recognized clinical entity for many decades.
      In this syndrome, hair becomes tightly wrapped around an appendage, usually that
      of an infant. Body parts involved include the finger, toe, penis, clitoris, and
      uvula. The end result of necrosis is also well documented. In this report, an 11
      month-old girl with hair tourniquet syndrome causing signs and symptoms of an
      acute strangulation is presented.

PMID- 15864372
TI  - Subacute appendicitis.

PMID- 15864373
TI  - Respiratory distress in a young infant.

PMID- 15864374
TI  - Relationship between thymidylate synthase (TS) genotype and TS expression: a
      tissue microarray analysis of colorectal cancers.
AB  - Response of colorectal cancers to 5-fluorouracil appears to be influenced by
      differences in thymidylate synthase (TS) expression. To explore the relationship
      between TS 5' genotype and expression, we analyzed paired tumor and normal tissue
      from 87 colorectal cancers by tissue microarray. A trend to an association
      between TS genotype and expression was observed, but the correlation was weak.
      Although the 2R homozygote was preferentially associated with TS expression
      (p<0.03), no relationship was observed for the 3R homozygote (p=1.0). The
      relationship between 5' TS genotype and TS expression is not simple. For clinical
      trials incorporating TS status, detection of TS expression in tumors by
      immunohistochemistry must still remain the benchmark over genotype.

PMID- 15864376
TI  - The 2004 WHO classification of bladder tumors: a summary and commentary.
AB  - The key points of the latest World Health Organization (WHO) classification of
      non-invasive urothelial tumors are the following: the description of the
      categories has been expanded to improve their recognition; a tumor with
      particularly good prognosis (papillary urothelial neoplasm of low malignant
      potential) no longer carries the label of 'cancer'; it avoids the use of
      ambiguous grading such as grade 1/2 or 2/3 (as done in the 1973 WHO
      classification); the group of noninvasive high-grade carcinoma is large enough to
      virtually contain all those tumors having biological properties similar to those
      seen in invasive urothelial carcinoma, and a similarly high level of genetic
      instability. This scheme is meant to replace the 1973 WHO classification, but the
      use of both the 1973 and the latest WHO classifications is recommended until the
      latter is sufficiently validated.

PMID- 15864375
TI  - Correlation of epidermal growth factor receptor expression with tumor
      microdensity vessels and with vascular endothelial growth factor expression in
      ovarian carcinoma.
AB  - We analyzed in advanced ovarian serous G3 carcinoma the correlation between
      epidermal growth factor receptor (EGFR) overexpression and tumor angiogenesis and
      their relation with clinical outcome. Microvessel density (MVD) and vascular
      endothelial growth factor (VEGF) were statistically correlated with disease-free
      interval and death from disease both in univariate and multivariate analyses
      while EGFR expression was not correlated with clinical outcome. MVD was
      significantly associated with progression of disease during chemotherapy while
      VEGF and EGFR expression were not correlated with responsiveness to chemotherapy
      (Fisher's exact test). VEGF expression was correlated with MVD (Fisher's exact
      test). EGFR showed a trend to correlation with MVD. Further studies focusing on
      the use of angiogenesis inhibitors in addition to EGFR inhibitors on ovarian
      carcinoma cells may produce therapeutic strategies in the selection of tailored
      therapies in ovarian cancer patients.

PMID- 15864378
TI  - A proposal for the adoption of a uniform metrical system for mitosis counting.

PMID- 15864379
TI  - An improved technique for mitosis counting.
AB  - Mitosis counting remains one of the most valuable prognostic indicators in tumor
      pathology; however, as currently carried out it is time consuming and not
      reproducible. In this study, 6 different pathologists, using different
      microscopes, arrived at widely different mitotic counts on the same slide,
      ranging from 4 to 16. These differences were mainly due to the different field
      areas of the various microscopes used and the method used for counting and
      recording. In evaluating the most active 10 HPF, the count ranged from 10 to 19.
      Instead, when an average of 40 fields was recorded, the range was 4-11. Using the
      mitosis/volume index, which expresses the number of mitotic figures per mm2 of
      viable tumor, the counts ranged from 8 to 10, a marked improvement. However, this
      method is complicated and not "user-friendly.'' We suggest a variation of the
      technique by which a 2 mm2 rectangle is drawn on a cover slip and mounted under
      the microscope, centered on the most mitotically active area of the tumor. The
      mitoses in that area are counted (=n) and the percent of viable tumor (=x%) is
      estimated under low magnification. The number of mitoses per mm2 of viable tumor
      (cs-MAI) is then calculated according to the formula Cs-MAI=100n/2x. Using this
      modified method, the range of mitoses counted by the different observers was very
      narrow (9 to 11), and the time required for the counting was only 5-10 minutes.

PMID- 15864381
TI  - Clinical implication of florid reactive follicular hyperplasia in Japanese
      patients 60 years or older: a study of 46 cases.
AB  - Florid reactive follicular hyperplasia (FRFH) of the enlarged lymph node in
      middle-aged or elderly patients requiring biopsy is a relatively uncommon
      phenomenon as compared with that in younger age groups. Between 1984 and January
      2004, we encountered 46 patients, aged 60 years or older, in whom histology of
      biopsied lymph node specimens showed inappropriate FRFH for the patient's age. An
      apparent cause of lymphadenopathy was initially identified in 17 cases (37%): 11
      with autoimmune disease and related disorders, 3 with cancer-reactive
      lymphadenopathy, 2 with Epstein-Barr virus-associated lymph node lesion
      exhibiting transient autoimmune-disease-like clinical findings, and 1 with
      atypical mycobacterial infection. Among 29 patients without specific etiology, 16
      patients (55%) exhibited histologic findings of progressive transformed germinal
      center (PTGC). Only 1 of our patients developed malignant lymphoma during the
      follow-up period. The present study indicates that PTGC is included in the
      etiology of FRFH in elderly Japanese patients as well as imbalance of the immune
      system such as autoimmune-disease-associated lymphadenopathy and idiopathic
      plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia. By in situ
      hybridization, Epstein-Barr virus genomes were demonstrated in only 6 (15%) of 39
      cases examined.

PMID- 15864380
TI  - Atypical adenomatous hyperplasia (adenosis) of the prostate: DNA ploidy analysis
      and immunophenotype.
AB  - Atypical adenomatous hyperplasia (AAH) of the prostate is a microscopic
      proliferation of small acini that may be mistaken for adenocarcinoma. Although
      some data suggest that AAH is associated with adenocarcinoma arising in the
      transition zone, the clinical significance of this lesion is uncertain. Therefore
      we studied the DNA ploidy pattern and immunophenotype of AAH as compared with
      nodular hyperplasia and well-differentiated adenocarcinoma in 23 formalin-fixed,
      paraffin-embedded, whole-mounted retropubic prostatectomies. Representative
      sections were immunostained for keratin 34beta-E12, chromogranin, bcl-2, c-erbB
      2, ki67-MIB1, and factor VIII (microvessel density). DNA ploidy was determined by
      image analysis and Feulgen-stained sections. There were rare scattered
      immunoreactive cells for chromogranin, bcl-2, and c-erbB-2 in nodular hyperplasia
      and AAH (mainly in the basal cell compartment) and in carcinoma. The ki67-MIB1
      labeling index was different between nodular hyperplasia and AAH (p<0.001) and
      carcinoma (p=0.003) but not between AAH and carcinoma (p=0.203). Microvessel
      density was different between AAH and carcinoma (p=0.001) but not between nodular
      hyperplasia and AAH (p=0.105) or carcinoma (p=0.0820). All foci of nodular
      hyperplasia, AAH, and carcinoma were diploid. Ploidy status and our selected
      panel of antibodies did not discriminate among these 3 entities reliably.

PMID- 15864382
TI  - Noninclusion-body infantile digital fibromatosis: a lesion heralding terminal
      osseous dysplasia and pigmentary defects syndrome.
AB  - This report describes the histologic and immunohistochemical features of a
      peculiar type of digital fibroma that shares some clinical and microscopic
      features with the more common inclusion-body type infantile digital fibromatosis.
      However, this type does not exhibit inclusion bodies and its cells are reactive
      for vimentin but not for actin. Significantly, it presents in combination with a
      constellation of other clinical findings, i.e., mainly positional and bone
      abnormalities of the fingers and toes, and skin pigmentary defects. Thus,
      noninclusion-body digital fibromatosis may represent the first clue for the
      diagnosis of the so-called terminal osseous dysplasia and pigmentary defects
      syndrome.

PMID- 15864383
TI  - So-called "inflammatory leiomyosarcoma'': a series of 3 cases providing
      additional insights into a rare entity.
AB  - Inflammatory leiomyosarcoma, a rare entity first described in 1995, has been
      characterized by smooth muscle differentiation, a near-haploid karyotype, and a
      surprisingly good prognosis. The morphology is similar to that of conventional
      leiomyosarcoma admixed with a chronic inflammatory infiltrate. Thus far, only 15
      cases have been reported in the English language literature. We report the
      clinical and pathological features of 3 additional cases of inflammatory
      leiomyosarcoma. Two women (ages 64 and 25, respectively) and 1 man (age 32)
      presented with a thigh, ovary, and lung mass, respectively. Inflammatory
      symptoms, such as anorexia, fever, night sweats, abdominal pain, and diarrhea,
      coincided with the thigh and ovarian primaries. Immunohistochemical studies
      revealed diffuse positivity for desmin and poor expression for other smooth
      muscle and skeletal muscle markers (muscle-specific actin [0/3], alpha-smooth
      muscle actin 1/3 [focal], calponin [1/3], caldesmon [0/3], and myogenin [0/3]).
      CD68 was diffusely positive in both the histiocytes and spindle cell component in
      all cases. Ultrastructural evaluation of 1 case (lung primary) lacked definitive
      smooth muscle differentiation. Cytogenetic analysis in 1 of 2 cases that were
      karyotyped, identified a near-haploid karyotype, which has been reported in other
      cases of inflammatory leiomyosarcoma. The other case showed 2 clonal populations
      of cells with interstitial deletions of the short arm of chromosome 8 and the
      long arm of chromosome 9, respectively. The case without cytogenetic data was
      intimately associated with an ovarian mature teratoma. These data also suggest
      that inflammatory leiomyosarcoma may lack smooth muscle differentiation,
      characterized by diffuse immunoreactivity for desmin but lack of immunoreactivity
      for alpha-smooth muscle actin, calponin, and caldesmon. In addition, 2 of the 3
      cases developed distant metastases to the lungs, which suggests that these
      lesions may have a worse prognosis than previously believed.

PMID- 15864384
TI  - Histopathological study of small (<2 cm) gastric carcinoma with signet-ring cell
      component: significance of the admixed glandular components.
AB  - Admixture of signet-ring cell carcinoma component (SIG) and glandular component
      (GC) is sometimes found in a gastric cancer. The aim of this study was to
      elucidate the biological behavior of the gastric cancer containing either SIG
      only (SIG-type tumor) or SIG admixed with GC (SIG-GC-type tumor). Forty-three
      cases of SIG-type tumor and 26 cases of SIG-GC-type tumor, less than 2 cm in
      largest diameter, were examined. Twenty-six cases (60%) of SIGs were less than 10
      mm in size, whereas only 3 cases (12%) of SIG-GCs were less than 10 mm in size
      (p<0.0001). Submucosal invasion by cancer cells was found in 12 cases of SIG-GCs
      but was not found in any of the SIGs. Those SIG-GCs showed gastric phenotype. It
      is important to note SIG-GC-type tumor for histopathological diagnosis.

PMID- 15864386
TI  - Tumefactive necrobiotic granulomas (nodulosis) of the pancreas in an adult with
      long-standing rheumatoid arthritis.
AB  - Rheumatoid nodules are well-documented clinical and pathologic lesions in
      patients with seropositive rheumatoid arthritis (RA). The current report
      documents the occurrence of rheumatoid nodulosis of the pancreas in an adult
      woman with a 7-year history of seropositive RA who presented with upper abdominal
      pain and was found to have multiple masses in the body and tail of the pancreas
      by imaging studies. An elevated serum pancreatic polypeptide (PP) and the
      development of new lesions in the pancreas prompted a subsequent distal
      pancreatectomy. The lesions in the pancreas proved to be necrobiotic palisading
      and hyalinizing granulomas upon pathologic examination. Also, of interest,
      elevation of serum PP has been observed in patients with RA and other systemic
      noninfectious and infectious inflammatory disorders in the absence of a
      pancreatic or intestinal neuroendocrine neoplasm.

PMID- 15864387
TI  - Mesothelioma of the tunica vaginalis testis: report of 2 cases with asbestos
      occupational exposure.
AB  - We report here 2 cases of malignant mesothelioma of the tunica vaginalis testis.
      A 67-year-old man with a left testicular mass was referred for left inguinal
      orchidectomy. Histologic examination showed a malignant mesothelioma of
      epithelial type. There is no evidence of recurrence at 2-year follow-up. The
      patient had been exposed to asbestos 12 years previously for a 30-year period. An
      80-year-old man presented a 5-year history of scrotal swelling. Clinical
      examination revealed a hydrocele. The patient underwent resection of the tunica
      vaginalis through scrotal incision. Microscopic examination showed a malignant
      mesothelioma of biphasic type. There is no evidence of recurrence at 2-year
      follow-up. The patient had been exposed to asbestos 52 years previously for a 5
      year period.

PMID- 15864388
TI  - Irinotecan-induced colitis.
AB  - Irinotecan (CPT-11) is a chemotherapeutic drug used to treat tumors by acting on
      malignant cells through inhibition of DNA topoisomerase I and inducing premature
      apoptosis. Major toxic effects of Irinotecan are myelosuppression and
      gastrointestinal (GI) toxicity, which limits the dose of administration,
      particularly severe diarrhea with a delay of onset. However, according to the
      literature, serious GI side effects are uncommon, comprising 3% of the reported
      cases. The mechanism of Irinotecan-induced delayed diarrhea is unknown and
      unpredictable. To our knowledge, this is the first case of colitis associated
      with Irinotecan administration for temporal glioblastoma documented by biopsies.
      The histopathologic findings are described and the potential mechanisms inducing
      such lesions are discussed.

PMID- 15864389
TI  - Congenital juvenile granulosa cell tumor of the testis in a fetus showing full
      69,XXY triploidy.
AB  - Testicular juvenile granulosa cell tumor (TJGCT) occurs predominantly in infancy
      and may be associated with sex chromosomal abnormalities. We report a fetus
      aborted because of cytogenetically confirmed complete XXY triploidy. External
      genitalia of the fetus were female, with a short and patent vagina. The tumor
      presented as an abdominal multicystic mass with typical histologic and
      immunohistological features of JGCT. It was connected with a tubular uterus-like
      structure. The other gonad was an inguinally localized testis that showed
      histologically a Sertoli cell adenoma. Malformations typical for triploidy were
      also present: agenesis of the corpus callosum, stenosis of the pulmonary ostium,
      and hypoplasia of the lungs and adrenals. To our knowledge this is the first case
      of TJGCT in a triploid fetus.

PMID- 15864390
TI  - Cutaneous melanoma metastatic to uterine adenomyoma: report of a case.
AB  - Rare cases of metastasis to uterine polyps have been reported in English
      literature but not, to the best of our knowledge, to uterine adenomyomas. All
      these cases are represented by breast cancer, most of them involving tamoxifen
      associated polyps. We first report a case of cutaneous malignant melanoma
      metastatic to uterine adenomyoma. A computed tomography scan did not reveal any
      further evidence of disease, suggesting that this metastatic localization may
      represent something more than a fortuitous case. Based on these observations it
      is suggested that a subset of malignant melanoma and breast cancer cells share a
      sort of "homing'' phenomenon to polypoid lesions of uterus, due probably to the
      presence of some chemokines and their specific receptors. Pathologists should be
      aware of this possibility in order to look carefully for metastatic implants in
      similar lesions. It is proposed that chemokine profile of neoplastic cells can be
      a useful tool in predicting metastatic targets.

PMID- 15864391
TI  - Pathologic features of necrotizing adenoviral prostatitis in an AIDS patient.
AB  - Adenovirus has been implicated as a cause of opportunistic infections in
      immunocompromised patients, frequently with multiorgan involvement and a fatal
      outcome. We describe a case of necrotizing adenoviral prostatitis in a 35-year
      old man with terminal AIDS and generalized adenoviral infection. The
      histopathologic findings of intraacinar necrotizing inflammation, prominent viral
      nuclear inclusions in residual epithelium, and mild T-lymphocyte and macrophageal
      inflammatory reaction were observed in the prostate. The presence of adenovirus
      was confirmed by electron microscopy and immunohistochemistry. Squamous
      metaplasia was present in the surrounding acini. This case of adenoviral
      prostatitis appears to be the first report of its kind in medical literature and
      demonstrates another aspect of the diversity of organ manifestations seen in this
      infection. This lesion should be included in the differential diagnosis of
      necrotizing prostatic diseases.

PMID- 15864392
TI  - Corpora albicantia-like bodies in cystic nephroma: yet another similarity to
      mixed epithelial stromal tumor of kidney.

PMID- 15864395
TI  - Rapid cognitive decline: searching for a definition and predictive factors among
      elderly with Alzheimer's disease.
AB  - The pattern and rate of cognitive decline in AD patients is far from uniform. In
      clinical practice, certain patients present episodes of rapid cognitive loss,
      whereas others deteriorate more progressively. At present time, there is little
      known about rapid decline in cognitive function in patients with AD, and moreover
      among older population. The main objective of this review was to elaborate a
      proposal of definition of rapid cognitive decline in order to facilitate its
      applicability into ordinary medical practice and to be relevant for clinical
      decision making in old patients with AD. After the literature review, our results
      from longitudinal prospective studies and our clinical practice experience, we
      propose the following definition of rapid cognitive decline: a four-point or
      greater loss on the MMSE within six months and the loss of at least one point on
      the MMSE during the following six months. After ELSA cohort's results, 11% of an
      AD population of 312 patients were rapid cognitive decliners, complying with our
      proposed definition. They represent a non-negligible proportion of the population
      afflicted by AD.

PMID- 15864396
TI  - Predictive factors for rapid loss on the mini-mental state examination in
      Alzheimer's disease.
AB  - OBJECTIVES: To seek predictors of rapid loss of cognition and to evaluate their
      frequency in a prospective study of patients suffering from Alzheimer's disease
      (AD). DESIGN: A one-year prospective study. METHODS: 312 AD patients from the
      memory clinic at Toulouse University Hospital, participants in the ELSA study,
      were enrolled. Rapid cognitive decline was defined as a 4-point or greater loss
      on the Mini-Mental State Examination (MMSE) in 6 months. Comprehensive geriatric
      and neuropsychological assessment was conducted at baseline, 6 months and one
      year. RESULTS: Seventy-nine (24.8%) patients presented rapid cognitive loss over
      6 months. The majority were stable at one year whereas 15 experienced continued
      rapid cognitive loss. Multivariate analysis showed that only the Mini Nutritional
      Assessment score (MNA) was correlated with rate of decline. Patients with rapid
      cognitive decline were also significantly more dependent at 6 months.
      CONCLUSIONS: Our findings demonstrate that rapid cognitive loss is frequent in AD
      patients, probably indicating underlying frailty. Future studies should lead to a
      practical approach to detecting these frail patients and to increasing preventive
      interventions.

PMID- 15864397
TI  - The relationship of functional status, nutritional assessment, and severity of
      illness to in-hospital mortality.
AB  - BACKGROUND: Prediction of in-hospital mortality may direct hospital resources
      towards those patients most at risk. A number of single domain risk instruments
      have been developed, indicating that functional status, nutritional assessment,
      and severity of illness individually predict in-hospital mortality. The
      interaction among these predictors is less well described. OBJECTIVE: To
      determine the relationship of functional status, nutritional assessment, and
      severity of illness to in-hospital mortality. DESIGN, SETTING, SUBJECTS: Cohort
      study of 1712 consecutive admissions over a one year period to an Internal
      Medical Service at a tertiary university teaching hospital. MAIN OUTCOME
      MEASURES: Death during hospital admission. RESULTS: Dependency in activities of
      daily living (OR = 3.37, 95% CI 1.78 to 6.37, p = 0.0002) and body mass index
      less than 20 (OR = 2.38, 95% CI 1.20 to 4.74, p = 0.01) predicted in-hospital
      mortality after adjusting for nutritional risk assessment, and severity of
      illness score. CONCLUSIONS: Impairment in functional status and low body mass
      index produce the best predictors of inhospital mortality, after adjusting for
      nutritional risk and severity of illness score. Among these factors, functional
      impairment may be amenable to correction.

PMID- 15864398
TI  - Laxative use and its relationship with straining in a London elderly population:
      free-living versus institutionalised.
AB  - BACKGROUND: The diagnosis of functional constipation according to Rome II
      criteria includes assessment of straining. However the prevalence in older adults
      is unknown. Moreover, laxative use increases with age, especially in the elderly.
      AIMS: to assess the prevalence of straining and its association with laxative use
      in free-living (FL) and institutionalised (INS) older adults. METHODS: 50 FL
      (mean age 74 years, 42% male) and 42 INS subjects (mean age 84 years, 36% male)
      were recruited. Straining to start and to finish defecation were prospectively
      recorded by subjects for 7 consecutive days in a bowel habit diary. Concurrently,
      the subjects recorded any laxative use during the 7 days study. Statistical
      analyses were performed using the Chi-square statistic. RESULTS: 20% of FL and
      65% of INS subjects recorded taking laxatives during the study week. Of the 40 FL
      subjects not taking laxatives, 30 had to strain to start on 25% or less of
      occasions and 36 had to strain to finish on 25% or less of occasions (chi(2) =
      7.2; p = 0.012 and chi(2) = 5.4; p = 0.041, respectively). In the INS group,
      although 64% of subjects taking laxatives had to strain on more than 25% of
      occasions, the Chi-square test was not statistically significant. CONCLUSIONS:
      From our results, it seems that laxatives were used appropriately in the FL, with
      the majority of those taking laxatives having to strain to start on more than 25%
      of occasions.

PMID- 15864399
TI  - A comparison of water turnover in older people in community and institutional
      settings.
AB  - BACKGROUND: Maintaining water balance is essential for health, but environmental
      factors, pathology and the ageing process can adversely affect water homeostasis.
      OBJECTIVE: This study examined the relationship between physical dependency and
      daily water turnover rate in an older population. DESIGN: Daily water turnover
      (DWT) was estimated, using deuterium oxide ((2)H(2)O) as a tracer for water, over
      two separate 7-day periods in summer and winter in two older populations. The
      independent group (N = 22) lived in their own homes and were self-caring. The
      dependent group (N = 15) lived in institutional care, and were more physically
      dependent. None of the subjects had significant mental impairment. Total body
      water (TBW) and DWT were estimated from the equilibration concentration of
      ingested (2)H(2)O and its subsequent elimination rate. RESULTS: The independent
      group had a median (range) age of 75(69-88) y, a mean Barthel Index (BI) of 19.8,
      and a mean Abbreviated Mental Test (AMT) score of 9.8. The dependent group were
      older (83(72-93) y), with a mean BI of 13 and a mean AMT of 9.3. Average median
      (range) DWT in the independent group was similar in summer (2.2(1.3-3.6) l.d(-1))
      and winter (2.1(1.4-3.6) l.d(-1)), but faster than in the dependent group
      (1.5(0.9-2.9) and 1.6(1.0-2.8) l.d(-1), respectively) during the same two
      periods. Median urine output in the independent group was similar in summer
      (1.7(0.8-3.3) l.d(-1)) and winter (1.7(0.9-3.2) l.d(-1)), but greater than in the
      dependent group (1.1(0.6-2.7) and 0.9(0.5-1.6) l.d(-1), respectively).
      CONCLUSION: These results show that the water turnover rate of many older people
      is low, and that intake may be affected especially in those with physical
      disability.

PMID- 15864400
TI  - Influence of cognitive impairment and comorbidity on disability in hospitalized
      elderly patients.
AB  - BACKGROUND: The effects of cognitive impairment and comorbidity on the prevalence
      of disability in elderly patients who are hospitalized in acute wards are not
      well defined. OBJECTIVES: To evaluate the role of comorbidity and cognitive
      impairment on the prevalence of disability in a cohort of hospitalized older
      patients. PATIENTS AND METHODS: This study included 179 patients aged 65 years
      and over admitted to the Geriatric Unit of the Casa Sollievo della Sofferenza
      Hospital, in Italy. Cognitive status was evaluated by means of the Mini Mental
      State Examination (MMSE) and Clinical Dementia Rating Scale (CDR); the functional
      status was evaluated according to the Activity of Daily Living (ADL) and
      Instrumental Activities of Daily Living (IADL) indices. Comorbidity was
      identified using the Cumulative Illness Rating Scale (CIRS index). RESULTS: Of
      the 179 patients enrolled 73 patients were diagnosed with dementia [Alzheimers'
      Disease (AD) = 49 patients, Vascular Dementia (VD) = 24 patients], 35 patients
      with Mild Cognitive Impairment (MCI) and 71 patients had no cognitive impairment.
      The severity of disability was significantly higher in patients with dementia
      (ADL = 3.1 +/- 2.1, IADL = 1.5 +/- 2.0) than patients with MCI (ADL = 5.1 +/-
      1.4, IADL = 5.2 +/- 2.2) (p < 0.0001) and patients without cognitive impairment
      (ADL = 5.5 +/- 0.9, IADL = 6.4 +/- 1.9) (p < 0.0001). No significant differences
      in CIRS index were observed between patients with dementia and MCI and no
      cognitive impairment patients (Dementia = 2.4 +/- 1.4 vs MCI = 2.9 +/- 1.4 vs No
      cognitive impairment = 2.7 +/- 1.2; p = 0.1). Moreover, a significant correlation
      between cognitive impairment and functional status (MMSE/ADL: r = 0.45, p =
      0.0001, MMSE/IADL: r = 0.54, p = 0.0001) but not between comorbidity and
      functional status (CIRS/ADL: r = 0.0007, CIRS/IADL: r = 0.040) was observed.
      Separating patients with dementia by diagnosis of AD or VD, no significant
      differences in MMSE (AD = 12.2 +/- 6.7 vs VD = 13.2 +/- 6.5, p = 0.6), CDR (AD =
      2.2 +/- 0.8 vs VD = 2.1 +/- 0.7, p = 0.6), ADL (AD = 3.1 +/- 2.1 vs VD = 3.0 +/-
      2.1, p = 0.8), IADL (AD = 1.3 +/- 1.9 vs VD = 2.0 +/- 2.2, p = 0.1) or CIRS (AD =
      2.2 +/- 1.5 vs VD = 2.8 +/- 1.3, p = 0.06) scores were observed. CONCLUSIONS:
      Cognitive impairment and not comorbidity, was significantly associated with
      disability in hospitalized older patients.

PMID- 15864401
TI  - An inexplicable oversight and a misconception in research.

PMID- 15864402
TI  - Dietary quality and social contact among a nationally representative sample of
      the older adult population in the United States.
AB  - BACKGROUND: To design appropriate health promotion programs for older adults, it
      is important to understand risk factors that influence dietary intake and
      quality. OBJECTIVE: Examine, by frequency and source of social contact,
      characteristics of a representative sample of older adults and, associations
      between these social contacts and quality of dietary intake. DESIGN: Data of 3194
      participants in NHANES III, ages 65 years and over, were analyzed. A summary
      score for social contact was developed based on frequency of telephone contact;
      get together with friends, relatives and neighbors; attendance at religious
      services; and attendance at club meetings. Dietary intake measures included,
      Healthy Eating Index (HEI) scores, calorie and nutrient intakes. Demographic,
      lifestyle and social variables were examined in association with social contact
      in logistic regressions. Associations between social contact and dietary intake
      were examined using linear regression. RESULTS: Compared to men and women with 4
      social contacts (HEI = 69.2 and 72.7)), those with one, two or three social
      contacts had significantly lower HEI scores (HEI of men = 62.6, 64.8, 67.5 and
      HEI for women = 65.7, 68.4, 70.3, respectively), consumed fewer calories and
      fewer servings of vegetables, fruit and variety when controlled for age and
      ethnicity. Associations were greatly attenuated when demographic and lifestyle
      variables were controlled for. Being a smoker, self-reporting poor health and
      needing help with personal or routine care were associated with lower social
      contact. CONCLUSIONS: Dietary intake is affected by a variety of factors
      including frequency of social contact. Outreach and screening, by community-based
      programs, may result in social and health benefits.

PMID- 15864403
TI  - Correlations of life-span variation parameters in 128 successive generations of
      Drosophila melanogaster with changes in atmospheric pressure and geomagnetic
      activity.
AB  - Correlations between the parameters of life-span (LS) distribution of Drosophila
      melanogaster, including mean LS (MLS) and the time of 10 and 90% population
      mortality, and some geophysical parameters that are usually beyond the control of
      researchers dealing with laboratory cultures, including atmospheric pressure,
      solar activity indices (Wolf's sunspot numbers and 2,800-MHz radio flux), and
      geomagnetic activity (planetary index, K(p)), were studied. Geophysical data were
      obtained from free-access official web sites of the National Oceanic &
      Atmospheric Administration of the US Department of Commerce and the Institute of
      Terrestrial Magnetism and Radiowave Propagation of the Russian Academy of
      Sciences. The geophysical parameters were calculated only for the period
      corresponding to 10 days of preimaginal development of the flies from egg to
      imago. Canonical correlation analysis, calculation of the non-parametric Spearman
      rank-order correlation coefficients, and graphical data analysis were used.
      Highly significant correlations between parameters of LS distribution in males
      and females and environmental factors, such as the atmospheric pressure on the
      4th and 5th day of development and geomagnetic activity indices (K(p)) on the 6th
      and 10th day of development were found, with correlation coefficients varying
      from 0.31 to 0.37 (P<0.02). Assuming a causal relationship between geophysical
      factors and LS, it may be hypothesized that energetically weak environmental
      factors determine the formation of LS oscillatory dynamics in laboratory
      populations. The possible mechanisms underlying the contribution of these
      environmental factors to the LS variation in successive generations are
      discussed.

PMID- 15864404
TI  - Meteorological effects on adult mosquito (Culex) populations in metropolitan New
      Jersey.
AB  - For two metropolitan New Jersey counties, monthly average adult mosquito (Culex)
      catch from New Jersey light trap data sets covering multiple decades is related
      to a number of meteorological factors. From June through August climatological
      conditions accounted for between 40% and 50% of the variation in average catch.
      In general, high monthly precipitation totals both in the month corresponding to
      the catch and the previous month were associated with increased trap catch.
      However, individual heavy rainfall events tended to reduce catch. Warm
      temperatures exerted a positive influence on mosquito abundance in June, but were
      associated with a low catch in August. Linear meteorological relationships
      explained only a small percentage of the variations in mosquito catch during May
      and September. During July, and particularly August, antecedent monthly catch
      also explained a significant portion of the variance in the contemporaneous
      catch. Over 60% of the variability in August catch could be attributed to the
      July population.

PMID- 15864406
TI  - Intact and deficient feature fusion in schizophrenia.
AB  - In patients with schizophrenia, early as well as late stages of information
      processing can be deficient. Therefore, it is important to determine the earliest
      occurrences of aberrant processing since deficits on these stages may cause
      abnormal processing on later, e. g. cognitive, levels. In order to investigate
      this issue in the visual domain, we studied one of the most basic feature
      integration mechanisms, namely feature fusion. Our results indicate that in
      schizophrenic patients this integration mechanism is qualitatively intact but
      reveals quantitative impairments that may influence later processing stages.

PMID- 15864407
TI  - The effects of clomethiazole on polysomnographically recorded sleep in healthy
      subjects.
AB  - Clomethiazole is widely used in European countries to treat alcohol withdrawal
      symptoms including delirium tremens. The current study aimed to explore the
      effects of clomethiazole on the sleep of healthy volunteers. We postulated both a
      hypnotic and a REM suppressive effect as well as the occurrence of a rebound
      phenomenon following three days of treatment with clomethiazole. The study group
      was composed of five men and five women. The probands were examined in the sleep
      laboratory throughout a course of seven nights. The first night was considered as
      the adaptation night and the second as the baseline night. Prior to nights 3 to
      5, probands took 384 mg clomethiazole at 22 hours. The 6th and 7th nights served
      to record potential effects of medication discontinuation. The current study
      confirms the indication in the scientific literature with regard to hypnotic and
      REM-suppressive effects of clomethiazole, as well as a rebound phenomenon
      following discontinuation of the medication. The effect of clomethiazole on the
      sleep EEG was most obvious in the first half of the night. The analysis of the
      polysomnogram in terms of each half of the night gave no indication of a rebound
      phenomenon during the second half. The REM sleep-suppressing component of
      clomethiazole is of great interest in connection with its use in treating
      delirium tremens. The rebound phenomenon in healthy controls after only three
      days of medication at a relatively low dosage of clomethiazole underscores the
      need to administer it in doses individually tailored to the extent of the alcohol
      withdrawal syndrome in the individual patient.

PMID- 15864408
TI  - Suitability of a batch in vitro fermentation model using human faecal microbiota
      for prediction of conversion of flaxseed lignans to enterolactone with reference
      to an in vivo rat model.
AB  - BACKGROUND: In vitro fermentation models have been used widely for studies of
      shortchain fatty acid (SCFA) formation from carbohydrates, whereas the
      suitability of these methods for enterolactone (ENL) formation has received less
      attention. AIM: The aim was to study the suitability of an in vitro fermentation
      model for prediction of bioconversion of lignans to ENL, to compare the approach
      with that of an in vivo rat model and to study the SCFA formation in both models.
      METHODS: Predigested samples of rye bran (R), flaxseed meal (F) alone, or in
      combination with rye bran (R&F) and a faecal control were incubated in an in
      vitro fermentation model using human faecal microbiota. In the in vivo experiment
      rats consumed a non-fibre control diet (C) or diets supplemented either with rye
      bran (R), flaxseed meal (F) alone, or with their combination (R&F) for four
      weeks. Enterodiol (END), ENL and SCFA concentrations were measured from in vitro
      faecal fermentation samples and from the intestinal contents of rats. Plasma ENL
      concentrations from rats were also measured. RESULTS: The highest ENL production
      was found in vitro with the F supplement (areas under curve: 740 +/- 4, 7,500 +/-
      400, 2,600 +/- 500 and 1,520 +/- 70 nmol x h for the R, F, R&F supplements and
      faecal control, respectively). In vivo, the concentration of ENL in caecal
      digesta from flaxseed meal was significantly (P < 0.05) enhanced by the presence
      of rye bran (medians 261, 407 and 24 nmol/g in the F, R&F and C groups,
      respectively). No correlation was found between the models regarding ENL
      production, possibly due to different responses to the presence of rye bran
      matrix, differences in microbiota or application of a batch in the in vitro
      fermentation model. Rye bran supplementation enhanced butyrate production both in
      vitro and in vivo. CONCLUSION: In vitro fermentation and the in vivo rat models
      responded differently to the presence of rye bran and no correlation with regard
      to the ENL formation from flaxseed lignans was observed.

PMID- 15864409
TI  - The relative bioavailability in humans of elemental iron powders for use in food
      fortification.
AB  - BACKGROUND: Bioavailability data in humans of elemental iron powders is limited
      although elemental iron is a common form of iron when used as a fortificant. AIM
      OF THE STUDY: The relative bioavailability (RBV) of seven elemental iron powders,
      five commercially available and two developmental are evaluated. In addition, one
      commercial electrolytic iron powder given with ascorbic acid (AA) was examined.
      METHODS: Based on a validated method this double-blinded randomized crossover
      study included three groups of male blood donors (n = 3*16) who were served rolls
      fortified with different elemental iron powders or ferrous sulfate (FeSO(4)) nine
      weeks apart. Blood samples were drawn every hour for six hours. RBV was obtained
      by comparing the increase in serum iron concentration induced by the elemental
      iron with the increase induced by FeSO(4). RESULTS: All elemental iron powders
      studied were significantly less well absorbed compared to FeSO(4). The
      electrolytic iron given with 50-mg AA was as well absorbed as FeSO(4) (molar
      ratio = 1:6, AA:Fe). The mean RBVs of the iron powders were: electrolytic (A-131,
      RBV = 0.65); electrolytic (Electrolytic, RBV = 0.59); carbonyl (Ferronyl, RBV =
      0.58); H-reduced (AC- 325, RBV = 0.56); H-reduced (Hi-Sol, RBV = 0.50); carbonyl
      (CF, RBV = 0.37); reduced (Atomet 95SP, RBV = 0.36). The reduced iron was
      distinguished by having significantly lower RBV (0.36) although no significant
      overall ranking was possible. CONCLUSION: Based on a validated method this
      doubleblinded cross-over study in humans showed that the evaluated elemental iron
      powders currently available for commercial use are significantly less well
      absorbed compared to FeSO(4). The results indicate that the reduced iron powder
      was absorbed to a lower extent compared to the other iron powders and only 36%
      compared to FeSO(4). Ascorbic acid seems to improve the bioavailability of
      elemental iron even though a rather low molar ratio is used. Thus, if confirmed,
      this enhancing effect of ascorbic acid on elemental iron when used as a
      fortificant could be used by co-fortifying them.

PMID- 15864410
TI  - Incidentally detected parafalcine chondrosarcoma.
AB  - Parafalcine chondrosarcoma is extremely rare, and may be difficult to
      differentiate preoperatively from falx meningioma. An 18-year-old woman presented
      with a parafalcine chondrosarcoma incidentally detected as a small lesion 2 years
      before admission, suggesting falx meningioma. Brain computed tomography and
      magnetic resonance imaging just before admission revealed the parafalcine lesion
      had increased by about nine times in volume during the last 2 years. Single
      photon emission computed tomography (SPECT) after intravenous administration of
      both thallium-201 chloride ((201)TlCl) and N-isopropyl-p-[(123)I]iodoamphetamine
      ((123)I-IMP) demonstrated no abnormal uptake of either tracer. Histological
      examination revealed classic low-grade chondrosarcoma. Parafalcine chondrosarcoma
      should be considered at this site if relatively rapid growth is observed. SPECT
      using (201)TlCl and (123)I-IMP may be useful to discriminate parafalcine low
      grade chondrosarcoma from meningioma or other tumours originating in this region.

PMID- 15864411
TI  - On some osteoporosis analyses.

PMID- 15864412
TI  - Association of single nucleotide polymorphisms in the promoter region of the pro
      opiomelanocortin gene (POMC) with low bone mineral density in adult women.
AB  - Among multiple factors influencing osteoporosis, genetic variations involved in
      bone-mineral metabolism can affect risks predisposing to the disease onset. Here,
      we studied single-nucleotide polymorphisms (SNPs) in the pro-opiomelanocortin
      (POMC) gene for possible association with bone mineral density (BMD) among 384
      adult Japanese women and observed significant correlation between adjusted BMD
      and three SNPs in the promoter region (r>0.14, p<0.01). The most significant
      correlation was observed for -2353G/A (r=-0.16, p=0.002); homozygous carriers of
      the major (G) allele had the highest BMD (0.405+/-0.054 g/cm2) while heterozygous
      carriers were intermediate (0.390+/-0.053 g/cm2) and homozygous A-allele carriers
      had the lowest BMDs (0.369+/-0.048 g/cm2). Although no association was detected
      between these SNPs and body weight or body mass index (BMI), significant
      association was detected between the -2313A/C genotype and plasma total
      cholesterol level (r=-0.12, p=0.019). We propose that POMC is among the likely
      susceptibility genes for osteoporosis and may also be involved in dyslipidemia.

PMID- 15864413
TI  - A single nucleotide substitution that abolishes the initiator methionine codon of
      the GLDC gene is prevalent among patients with glycine encephalopathy in
      Jerusalem.
AB  - Glycine encephalopathy (GE) (non-ketotic hyperglycinemia) is an autosomal
      recessive neurometabolic disease caused by defective activity of the glycine
      cleavage system. Clinically, patients present usually in the neonatal period with
      hypotonia, encephalopathy, hiccups and breath arrests with or without overt
      seizures. GE is considered rare, but its incidence is relatively high in several
      geographical areas around the world. We report a novel mutation causing GE in six
      extended Arab families, all from a small suburban village (population 5,000). A
      methionine to threonine change in the initiation codon of the glycine
      decarboxylase gene led to markedly reduced glycine decarboxylase mRNA levels and
      abolished glycine cleavage system activity.

PMID- 15864414
TI  - Gastroparesis after a pylorus-preserving pancreatoduodenectomy.
AB  - Gastroparesis after a pylorus-preserving pancreatoduodenectomy has two main
      aspects, namely early gastric stasis and subsequent postprandial delayed gastric
      emptying. Early gastric stasis producing an excessive amount of gastric juice
      during the immediate postoperative period might be caused by the absence of phase
      III activity of the gastric migrating motor complex (MMC), and such symptoms
      usually subside within a month or two. Subsequent postprandial delayed gastric
      emptying leading to belching, fullness of the stomach, nausea, and vomiting after
      the resumption of oral intake normally continues for up to 6 months before
      complete recovery. There are many possible mechanisms to explain these phenomena.
      The early recovery of phase III of the MMC does not necessarily predict an early
      relief of postprandial delayed gastric emptying, thus suggesting that these two
      phenomena are caused by various mechanisms. The phenomena, mechanisms, and
      treatment strategies for gastroparesis after pylorus-preserving
      pancreatoduodenectomy are described in this review.

PMID- 15864415
TI  - Significant clinical differences in primary hyperparathyroidism between patients
      with and those without concomitant thyroid disease.
AB  - PURPOSE: We evaluated the differences in diagnosis and treatment for primary
      hyperparathyroidism (pHPT) in patients with and those without concomitant thyroid
      disease. METHODS: One hundred and ten patients with pHPT underwent parathyroid
      localization and thyroid examination by ultrasonography (US) and sestamibi
      scintigraphy (MIBI). The clinical and biochemical findings, parathyroid
      localization, and operations performed were compared in 49 patients without
      thyroid disease and 61 patients with thyroid disease. RESULTS: Asymptomatic
      hypercalcemia was significantly more prevalent in patients with concomitant
      thyroid disease (88.5%) than in those without thyroid disease (49.0%) (P < 0.01).
      The mean serum calcium was significantly higher and the inorganic phosphate level
      was significantly lower in patients without concomitant thyroid disease than in
      those with concomitant thyroid disease (P < 0.05, P < 0.01, respectively). The
      pathologic parathyroid gland was identified significantly more often in patients
      without concomitant thyroid disease than in those with concomitant thyroid
      disease both by US and MIBI (P < 0.05). Unilateral exploration was performed more
      often in patients without thyroid disease than in those with thyroid disease (P <
      0.01). CONCLUSION: Primary hyperparathyroidism was diagnosed at an earlier stage
      in patients with concomitant thyroid disease. Thyroid disease concomitant with
      pHPT influenced parathyroid localization as well as the indication for minimally
      invasive parathyroidectomy.

PMID- 15864416
TI  - Surgical treatment of superior sulcus tumors.
AB  - PURPOSE: To access the clinical outcome of patients with superior sulcus tumor.
      METHODS: We reviewed the records of 16 patients who underwent surgery for a
      superior sulcus tumor between 1988 and 2003, focusing on the type of surgery.
      RESULTS: All 16 patients underwent en bloc lung and chest wall resection, which
      was done as pneumonectomy in 1 patient and lobectomy in 15. Complete resection
      was achieved in 11 patients, but incomplete resection was done in 5 patients
      because microscopic examination revealed positive surgical margins. Eight
      patients underwent partial vertebrectomy and 1 patient had combined resection of
      the subclavian artery. There was no postoperative mortality. All patients
      received pre- or postoperative adjuvant therapy, or both. The overall 5-year
      survival rate was 31.0%. The 5-year survival rate was higher after complete
      resection than after incomplete resection (59.3% vs 0%, P = 0.08). Patients who
      underwent complete resection for vertebral invasion and those who did not had 5
      year survival rates of 66.7% and 0%, respectively (P = 0.17). Patients who
      underwent preoperative induction therapy followed by complete resection and those
      who did not had 5-year survival rates of 80% and 0%, respectively (P = 0.009).
      CONCLUSION: Although superior sulcus tumors are still complex, preoperative
      induction therapy followed by complete resection seemed effective for prolonging
      survival.

PMID- 15864417
TI  - Absent mRNA accumulation of Th1 or Th2 cytokines in heart allografts with
      chimerism-based drug-induced tolerance.
AB  - PURPOSE: We recently described using cyclophosphamide (CP) plus busulfan (BU) to
      create drug-induced skin and heart allograft tolerance capable of regularly
      overcoming fully H-2 mismatched barriers in mice. The present study investigates
      the intragraft mRNA expressions of Th1 and Th2 cytokines. METHODS: This method
      consists of the intravenous (i.v.) injection of 1 x 10(8) allogeneic spleen cells
      on day 0, the intraperitoneal injection of 200 mg/kg CP and 30 mg/kg BU on day 2,
      and the i.v. injection of 1 x 10(7) T cell-depleted allogeneic bone marrow cells
      from the same strain of mice on day 3. Heart grafting (HG) was performed on day
      28. Chimerism in the peripheral blood was monitored by flow cytometric (FCM)
      analysis. The frequency of certain V(beta) families was determined by FCM to
      assess deletion of donor-reactive T cells. Th1 (interleukin [IL]-2, interferon
      [IFN]-gamma) and Th2 (IL-4, IL-10) cytokine expression in the heart grafts was
      analyzed with reverse transcription-polymerase chain reaction. RESULTS: In a
      fully MHC mismatched combination of B10.D2 (H-2d, IE+) --> B10 (H-2b, IE-),
      B10.D2 heart grafts were accepted permanently in a donor-specific manner, mixed
      chimerism was observed, and IE-reactive V(beta)11+ T cells were specifically
      reduced in the periphery from the recipient B10 mice. In the donor B10.D2 heart
      grafts, there was no accumulation of Th1 (IL-2, IFN-gamma) or Th2 (IL-4, IL-10)
      cytokines. CONCLUSIONS: These results show that the drug-induced tolerance we
      established can regularly induce long-lasting heart allograft tolerance without
      intragraft mRNA accumulation of Th1 or Th2.

PMID- 15864418
TI  - Hospitalization after open colectomy: expectations and practice in general
      surgery.
AB  - PURPOSE: There is increasing pressure to reduce the length of stay (LOS) in
      hospital after colectomy. To assess the impact of unintended variations on LOS,
      actual discharge management was compared with the expectations expressed by
      general surgeons. METHODS: We retrospectively examined 262 patients who underwent
      elective open colectomy. The effects of patient demographics, surgical variables,
      and functional recovery on postoperative LOS were assessed in univariate and
      multivariate models. We also used a structured questionnaire to assess the
      expectations of surgeons regarding criteria affecting patient discharge. RESULTS:
      The median LOS was 11 days, which was univariately correlated with morbidity,
      bowel movement, oral feeding, mobilization, surgeon, rectal procedures,
      comorbidity, type of analgesia, blood transfusion, and colorectal cancer.
      According to the multivariate analysis, morbidity (P < 0.001), colorectal cancer
      (P = 0.026), rectal procedure (P = 0.037), and analgesia (P = 0.04) were
      correlated with LOS. The surgeons we interviewed believed that discharge should
      be based on the return of bowel movement and the absence of morbidity. By
      discharging our patients on postoperative day 5 or 6, these criteria would have
      been respected in 84% and 88%, respectively. CONCLUSION: Prolonged
      hospitalization after colectomy persists when critical pathways are not observed
      and there is a lack of institutional pressure to reduce to the LOS. Many factors
      affect the delay in patient discharge, possibly reflecting unwanted variation
      rather than the surgeons' expectations.

PMID- 15864419
TI  - A clinicopathological investigation of "tumor nodules" in colorectal cancer.
AB  - PURPOSE: Tumor nodules (tn) have been histologically identified within the fatty
      tissue or the detached fatty tissue around dissected lymph nodes, or else picked
      up as lymph nodes from resected specimens with no lymph node components. The TNM
      classification of malignant tumors provides a description of how to deal with tn,
      but there has so far been no description within the Japanese classification of
      colorectal carcinoma. The aim of this study was to determine whether we should
      regard tn as metastatic lymph nodes from the viewpoint of prognosis. METHODS: A
      total of 544 patients who underwent a resection of colorectal adenocarcinoma
      between 1985 and 1995 were reviewed. RESULTS: Tumor nodules were found in 54
      (17.6%) of 307 colon cancer patients, and in 41 (17.3%) of 237 rectal cancer
      patients. We classified the curability A patients into four groups for both colon
      and rectal cancer; positive lymph nodes with tn (Group A), negative lymph nodes
      with tn (Group B), positive lymph nodes without tn (Group C), and negative lymph
      nodes without tn (Group D). The prognosis was not significantly different between
      Groups A, B, and C, but it was significantly different between Group D and Groups
      A, B, and C (P < 0.01) in both the colon and the rectum. CONCLUSION: From the
      viewpoint of prognosis, it thus appears justifiable to regard tn as lymph node
      metastasis.

PMID- 15864420
TI  - Portal hypertensive gastropathy after surgery for biliary atresia.
AB  - PURPOSE: To clarify the correlation between portal hypertensive gastropathy (PHG)
      and clinical features after surgery for biliary atresia (BA). METHODS: Routine
      upper gastrointestinal endoscopies were done over 3 years in 27 children who
      underwent surgery for BA. We reviewed the recorded endoscopic findings, and
      retrospectively diagnosed PHG according to McCormack's criteria. The differences
      in clinical features, such as endoscopically treated gastroesophageal varices and
      the results of routine laboratory tests, were compared between the children with
      PHG (PHG group) and those without PHG (non-PHG group). RESULTS: Nine (33%) of the
      27 children had PHG. Although there was no significant difference in age between
      the PHG and non-PHG groups, the frequency of past endoscopic variceal treatments
      was significantly higher in the PHG group (3.0 +/- 3.0 vs 0.6 +/- 1.5 times, P =
      0.01). The PHG group also had lower white blood cell and platelet counts, at 3008
      +/- 2411 vs 5527 +/- 2938/mm3 (P < 0.05) and 6.0 +/- 3.4 vs 13.9 +/- 4.7 x
      10(4)/mm3 (P = 0.0001), respectively; higher serum aspartate aminotransferase,
      total bile acid, and total bilirubin levels at 80 +/- 31 vs 46 +/- 29 U/l (P <
      0.05), 161 +/- 93 vs 64 +/- 88 U/l (P < 0.05), and 4.8 +/- 5.6 vs 1.0 +/- 0.8
      mg/dl (P < 0.01), respectively; and lower prothrombin time, albumin, and
      cholinesterase levels, at 66 +/- 16 vs 79% +/- 14% (P < 0.05), 3.6 +/- 0.8 vs 4.1
      +/- 0.5 g/dl (P < 0.05), and 2158 +/- 925 vs 3376 +/- 700 U/l (P < 0.001),
      respectively. CONCLUSION: Portal hypertensive gastropathy was found in 33% of
      children after surgery for BA. The factors contributing to the development of PHG
      were frequent endoscopic treatments of gastroesophageal varices, liver
      dysfunction, and hypersplenism.

PMID- 15864421
TI  - Effective 6-hour preservation in non-heart-beating donor canine lungs with
      topical cooling: assessment from histopathological aspects.
AB  - PURPOSE: This study assesses the possibility of preserving and transplanting non
      heart-beating donor (NHBD) lungs under topical cooling for 6 h. METHODS: The
      donor dogs were killed and heparinized after cardiac arrest. After 10 min of
      cardiac massage, the bilateral lungs were deflated. In group 1 (n = 6), the
      recipient dogs were transplanted and the lungs preserved at 4 degrees C for 6 h.
      In group 2 (n = 2), the recipients received lungs preserved at room temperature
      for 4 h. In both groups the right main bronchus, pulmonary artery, and pulmonary
      vein were clamped and ventilated to examine the lung function. RESULTS: The mean
      total ischemic time before reperfusion was 7 h 48 min (group 1) and 5 h 55 min
      (group 2). All dogs in group 1 survived with excellent hemodynamics and gas
      exchange function. Both dogs in group 2 revealed congestion immediately after
      reperfusion, and consequently died. CONCLUSIONS: We concluded that it is possible
      to use NHBD lungs for clinical lung transplantation if topical cooling can be
      initiated soon after irreversible cardiac arrest. Topical cooling of NHBD lungs
      allows at least 6 h for preparation before transplantation.

PMID- 15864422
TI  - Quantitative gene expression analysis by cDNA microarray during liver
      regeneration after partial hepatectomy in rats.
AB  - PURPOSE: It is speculated that genetic regulation plays an important role during
      liver regeneration. We conducted this study to analyze quantitative gene
      expression during liver regeneration after partial hepatectomy. METHODS: Sixty
      male Wistar rats were randomly assigned into ten groups of six. One group of rats
      was killed preoperatively and the other nine groups were killed 2, 4, 6, 12, 24,
      48, and 72 h, and 5 and 7 days after 70% partial hepatectomy, respectively. The
      remnant livers were isolated for mRNA extraction. A mass survey of gene
      expression by cDNA microarray carrying 6144 polymerase chain reaction-amplified
      cDNA fragments was prepared by an arraying machine. The microarray images were
      scanned, digitized, and analyzed using a flatbed scanner. RESULTS: The variations
      in gene expression were classified into 72 different patterns including a pattern
      with a single peak, 2, 4, 6, 12, and 72 h, and 5 and 7 days after partial
      hepatectomy. The other patterns included double peaks, enhancing trend,
      diminished trend, protruding curve, excavated curve, and various mixed types.
      Each category of gene expression pattern contained 40-218 different proto
      oncogenes. CONCLUSION: The quantitative gene expression profiles have important
      implications, warranting further investigation of the genetic mechanisms involved
      in the process of liver regeneration.

PMID- 15864423
TI  - Elevated basal calcitonin levels in a patient with a hurthle-cell carcinoma of
      the thyroid and neuroendocrine differentiation: report of a case.
AB  - A thyroid nodule with elevated plasma levels of calcitonin is usually suggestive
      of a medullary thyroid carcinoma (MTC); however, thyroid and extrathyroid
      conditions have been reported with elevated plasma calcitonin levels in the
      absence of MTC. We report the case of a patient with a thyroid nodule and an
      elevated basal plasma calcitonin level of 315 pg/ml (normal value <100 pg/ml) who
      underwent a left hemithyroidectomy. Interestingly, histopathological examination
      revealed a Hurthle-cell carcinoma with positive neuroendocrine (NE) markers such
      as calcitonin and synapthophysin, but not with chromogranin staining. Thus, we
      discuss the phenomenon of non-NE tumors showing positivity for NE markers.

PMID- 15864424
TI  - Delayed discovery of diaphragmatic injury after blunt trauma: report of three
      cases.
AB  - Blunt diaphragmatic injury is an increasingly common occurrence, frequently
      associated with considerable comorbidity. This injury is often missed at the time
      of the initial event, but may present some time later. We report three cases of
      diaphragmatic injury diagnosed 3 weeks, 6 months, and 12 years after the original
      diaphragmatic injury, respectively. Two of the injuries resulted from side-impact
      road traffic accidents and one followed a fall from a height. Gastrointestinal
      obstruction and respiratory compromise were the major presenting symptoms. All
      three patients were managed with a thoracotomy and the defect was closed without
      the need for prosthetic mesh. They all recovered uneventfully and have remained
      well since.

PMID- 15864425
TI  - Spinal destruction induced by chronic contained rupture of an abdominal aortic
      aneurysm: report of a case.
AB  - We report a case of spinal destruction caused by chronic contained rupture of an
      abdominal aortic aneurysm (AAA). The patient was a 73-year-old man who had
      undergone coronary artery bypass grafting, sigmoidectomy for colon cancer, and
      axillofemoral bypass with AAA resection within months of each other, 3 years
      earlier. Abdominal computed tomography and magnetic resonance imaging showed
      destruction of the 12th thoracic and 1st lumbar vertebrae. The possibility of a
      metastatic spine tumor prompted us to consult the orthopedic surgeons, who
      recommended a spinal percutaneous needle aspiration biopsy. However, the
      cardiovascular surgeons diagnosed chronic contained rupture of an inflammatory
      AAA. The patient gradually improved with antimicrobial treatment, but died of
      disseminated intravascular coagulation the following year. The definitive
      diagnosis was confirmed by autopsy. We report this case for its educational
      value, considering the serious consequences that might have occurred had we
      attempted to biopsy the lesion.

PMID- 15864426
TI  - Incarcerated recurrent rectal prolapse with ileal strangulation: report of a
      case.
AB  - We report a rare case of incarcerated rectal prolapse with ileal strangulation
      occurring after a Gant-Miwa procedure with anal encircling (Thiersch's procedure)
      for recurrent rectal prolapse. The patient was a 78-year-old woman who presented
      to our outpatient clinic the day after sudden rectal protrusion had occurred. She
      had undergone a Gant-Miwa procedure for rectal prolapse 4 years previously, and
      another Gant-Miwa procedure with anal encircling for recurrent rectal prolapse 18
      months earlier. The patient attempted to reduce the prolapse manually, but was
      unsuccessful. On admission, a 10 x 4-cm semispherical mass was observed extra
      anally, with a necrotic surface. We performed an emergency laparotomy, which
      rerealed a prolapse of the anterior wall of the rectum with part of the ileum
      protruding into the sac formation. Thus, we resected the incarcerated ileum
      followed by primary anastomosis and proctectomy (Hartmann's procedure) with good
      results. This case demonstrates that ileal strangulation can occur as a
      complication of rectal prolapse recurrence after perineal repair.

PMID- 15864427
TI  - Appendix carcinoid found incidentally during excision of a choledochal cyst:
      report of a case.
AB  - We report the case of a 13-year-old girl in whom an appendix carcinoid was found
      incidentally during excision of a choledochal cyst. Although incidental carcinoid
      tumors of the extrahepatic bile ducts have been reported, to the best of our
      knowledge this is the first published case of a choledochal cyst associated with
      an appendix carcinoid. We present this case to highlight the importance of
      conducting a thorough exploration of all quadrants of the abdomen before closure.

PMID- 15864428
TI  - Primary malignant peritoneal mesothelioma in an incarcerated groin hernia: report
      of a case.
AB  - Malignant peritoneal mesothelioma arising from the inguinal hernia sac is rare.
      We report the case of a 71-year-old man examined in our emergency department for
      a bilateral inguinoscrotal hernia, which was recurrent in the right groin, and
      primary and incarcerated in the left groin. An emergency exploratory operation
      revealed a firm mass, 10 cm in diameter, in the left inguinal hernia sac. The
      remaining peritoneal surface appeared macroscopically normal. Therefore, we
      resected the mass and performed a Rutkow hernioplasty. The patient was discharged
      after a short, uneventful recovery, and was referred to the oncology department
      for adjuvant therapy. He is now well and asymptomatic with no evidence of
      ascites, 26 months after his operation. A mesothelioma of the hernial sac
      peritoneum was the final histological diagnosis.

PMID- 15864429
TI  - Purification and characterization of a soluble recombinant human ST6Gal I
      functionally expressed in Escherichia coli.
AB  - A soluble and active form of recombinant human ST6Gal I was expressed in
      Escherichia coli. The gene encoding the soluble form of ST6Gal I lacking the
      membrane and cytosolic regions was introduced into a bacterial expression vector,
      pMAL-p2X, fused in frame with a maltose-binding protein (MBP) tag. Low
      temperature cultivation at 13 degrees C during IPTG-induction significantly
      improved both solubility and MBP-tagging of the recombinant enzyme expressed in
      bacteria. The supernatant prepared by disruption of the cells demonstrated sialic
      acid transfer activity to both an oligosaccharide and a glycoprotein,
      asialofetuin, indicating that the enzyme expressed in bacteria is soluble and
      active. The MBP-tagged enzyme was efficiently purified by a combination of cation
      exchange column and amylase-conjugated agarose column chromatography. The
      purified recombinant enzyme exerted enzymatic activity even in the absence of
      detergents in the reaction mixture. Acceptor substrate specificity of the enzyme
      was marginally different from that of rat liver ST6Gal I. These observations
      suggest that membrane and cytosolic regions of ST6Gal I may affect the properties
      of the enzyme. The purified recombinant enzyme was applied to convert
      desialylated fetuin to resialylated fetuin. Lectin blotting demonstrated that
      resialylated fetuin possesses a single Neu5Ac alpha 2-6 residue. The resialylated
      fetuin efficiently blocked hemagglutination induced by influenza virus strain
      A/Memphis/1/71 (H3N2), indicating that resialylated carbohydrate chains on the
      protein are so active as to competitively inhibit virus-receptor interaction. In
      conclusion, soluble recombinant ST6Gal I obtained using our bacterial expression
      system is a valuable tool to investigate the molecular mechanisms of biological
      and pathological interactions mediated via carbohydrates.

PMID- 15864430
TI  - Structural features of the lysosomal hydrolase mannose 6-phosphate uncovering
      enzyme.
AB  - The uncovering enzyme (UCE) removes N-acetylglucosamine from lysosomal enzymes to
      uncover the mannose 6-phosphate (Man-6-P) determinant necessary for targeting
      these enzymes to lysosomes. Failure to create the Man-6-P determinant is one
      cause of lysosomal storage diseases. Despite its medical importance, little
      structural information about UCE is available. In this report we have developed a
      model for the membrane proximal portion of the lumenal domain of UCE based on the
      structure of the EFG-3 and -4 domains of the extracellular segment of the beta
      chain of integrin alpha Vbeta 3. In this model the EGF-like domains of UCE
      (residues 285-345) are predicted to form a rod-shaped stalk region, similar to
      the stem region in Golgi glycosyltransferases. This stalk causes the proposed
      catalytic domain (residues 1-277) to be extended away from the Golgi membrane. A
      portion of the proposed catalytic domain (residues 85-256) resides in Cluster of
      Orthologous Group (COG) 4632 with four bacterial proteins but is not homologous
      to any known eukaryotic proteins. Thus, UCE may have evolved from the fusion of a
      unique catalytic domain with a common EGF-like stalk domain. We have determined
      by mass spectrometry that the four disulfide bonds of the proposed catalytic
      domain are located between Cys(2)-Cys(172), Cys(66)-Cys(99), Cys(83)-Cys(274),
      and Cys(258)-Cys(265). Finally, we determined that four of the six potential N
      linked glycosylation sites are glycosylated (Asn 159, Asn 165, Asn 247, and Asn
      317) in COS cells.

PMID- 15864431
TI  - Expression of complex-type N-glycans in developmental periods of zebrafish
      embryo.
AB  - As a first step to elucidate a role of N-glycans in development of vertebrates,
      we analyzed structures of the glycans expressed in early stages of zebrafish
      embryo. N-glycans were prepared from zebrafish embryos at several developmental
      stages followed by tagging with a fluorophore, 2-aminopyridine. The labeled
      glycans were analyzed by two modes of HPLC's. The comparison of the elution
      profiles of HPLC's unveil the change of the oligosaccharide structure during the
      development. These peaks were merely detected during 4-7 h after fertilization,
      however, increased from 12 h, and at 15 h a fairly amount of them was appeared.
      Structure analysis revealed that they were bianntenary complex-type N-glycans
      with or without fucose and/or bisecting N-acetylglucosamine residues. These
      results suggest that the complex-type N-glycans are concerned in some
      developmental event from segmentation period downward in zebrafish.

PMID- 15864432
TI  - PNA-binding glycans are expressed at high levels on horse mature and immature T
      lymphocytes and a subpopulation of B lymphocytes.
AB  - In mammals, the binding of peanut agglutinin (PNA) on the plasma membrane defines
      subpopulations among lymphocytes from peripheral blood and lymphoid organs. PNA
      binds Galbeta 1,3GalNAc residues provided that they are not sialylated. Here, we
      studied the expression of PNA-binding glycans on healthy horse peripheral blood,
      thymus, lymph node and spleen lymphocytes. We first demonstrated the binding
      specificity of PNA for galactose residues by competition experiments and the
      inhibitory role of sialic acids in PNA binding by sialidase digestion. Unlike
      human and murine lymphocytes, all equine lymphocytes were found positive by flow
      cytometry analysis. Double-staining analyses showed that lymphocytes expressing
      high levels of PNA-binding glycans (PNA(high) lymphocytes) were made up of the
      great majority of CD5(+), CD4(+) and CD8(+) cells, and of 30 and 50% of sIg
      bearing lymphocytes in peripheral blood and in lymph nodes or spleen,
      respectively. Lectin histochemistry suggested that lymph node germinal centres
      contained PNA(high) B cells. Contrary to what is found in humans and mice, PNA
      staining intensity on CD5(+), CD4(+) and CD8(+) cells did not differentiate
      immature from mature T lymphocytes in the equine thymus. The functional
      consequences of these differences are discussed.

PMID- 15864433
TI  - Mutational studies on endo-beta-N-acetylglucosaminidase D which hydrolyzes core
      portion of asparagine-linked complex type oligosaccharides.
AB  - Endo-beta-N-acetylglucosaminidase D (Endo D) produced by Streptococcus pneumoniae
      hydrolyzes the di-N-acetylchitobiose structure in the core of complex-type
      asparagine-linked oligosaccharides, and has a molecular weight of 180 kDa. A
      truncated Endo D of 102 kDa in which 134 N-terminal amino acids and 599 C
      terminal amino acids were deleted, still retained the enzymatic activity. The
      truncated Endo D has specificity indistinguishable from the intact enzyme, and
      also acted on the core structure of asparagine-linked oligosaccharides attached
      to intact IgG. Because of its lower molecular weight, the truncated enzyme may be
      useful as a tool for protein deglycosylation. The entire region of the truncated
      Endo D had 32% sequence identity to endo- beta-N-acetylglucosaminidase BH (Endo
      BH) from Bacillus halodurans, which acted on high-mannose type oligosaccharides.
      Chimeric constructs of the truncated Endo D and Endo BH showed no activity.
      Glutamic acid 324 (E 324) in Endo D is conserved in Endo BH and Endo M, and is an
      essential amino acid in Endo M. Mutation of E324 abolished Endo D activity. The
      specificity of Endo D for complex type oligosaccharides is probably defined by
      multiple domains in the Endo D structure.

PMID- 15864434
TI  - High molecular weight neoglycoconjugates for solid phase assays.
AB  - Adsorption of a carbohydrate on solid phase is the necessary stage of the
      immunosorbent assay (ELISA) and analogous methods of the study of carbohydrate
      protein interaction. Usually physical adsorption on polystyrene requires a high
      concentration of conjugated carbohydrate and, thus, enormous consumption of it.
      In this study, we explored two approaches allowing more rational use of
      oligosaccharide (Glyc). The first of them is based on the covalent immobilization
      of neoglycoconjugates on the NH(2)-modified polystyrene; the second one is based
      on the elevated adherence of high m.w. neoglycoconjugates to polystyrene.
      Covalent immobilization of polyacrylamide conjugates, Glyc-PAA, provided a
      possibility to solve the problem, but the nonspecific binding of antibodies in
      ELISA proved to be unacceptably high. At the same time, the increase of the Glyc
      PAA m.w. from 30 kDa to 2,000 kDa allowed a 10-20 fold decrease of its
      consumption, when using physical adsorption, whereas the assay background
      remained at the low level. The amount of 2,000 kDa Glyc-PAA that is sufficient
      for the coating of a standard 96-well plate corresponds to the nanomole level of
      oligosaccharide, this providing a possibility to use saccharides that are
      available in a very limited amount when studying the carbohydrate-protein
      interaction with solid-phase techniques.

PMID- 15864435
TI  - Regulation of sialyl-Lewis x epitope expression by TNF-alpha and EGF in an airway
      carcinoma cell line.
AB  - Sialyl-Lewis x epitopes and MUC5AC protein are known to be overexpressed in
      mucins secreted by patients suffering from various respiratory diseases. To
      investigate the mechanisms by which airway inflammatory agents mediate the
      expression of sialyl-Lewis x epitopes and MUC5AC mucin, we examined the effects
      of tumor necrosis factor (TNF)-alpha and epidermal growth factor (EGF) in the
      human lung carcinoma cell line, NCI-H292. Basal expression levels of hST3GalIV,
      FUT3 and C2/4GnT mRNA, involved in the biosynthesis of sialyl-Lewis x, were
      higher than those of other glycosyltransferases in NCI-H292 cells. TNF-alpha
      induced expression of hST3GalIV, FUT3, C2/4GnT and MUC5AC mRNAs in NCI-H292
      cells. When cells were pretreated with U73122, a phosphatidylinositol
      phospholipase C (PI-PLC) inhibitor, the expression of these glycosyltransferase
      mRNAs was suppressed. Treating cells with EGF induced the down-regulation of
      these glycosyltransferase mRNAs and sialyl-Lewis x epitopes, while inducing an
      increase in expression of MUC5AC mRNA. These EGF-mediated effects on the
      glycosyltransferase and MUC5AC mRNAs were blocked when cells were first exposed
      to AG1478, an EGF receptor tyrosine kinase inhibitor. These findings suggest that
      the expression of sialyl-Lewis x epitopes, which is regulated separately from the
      expression of MUC5AC protein, may be controlled through pathways such as the EGF
      receptor tyrosine kinase and PI-PLC signaling cascades in NCI-H292 cells.

PMID- 15864436
TI  - Activation of CMV promoter-controlled glycosyltransferase and beta -galactosidase
      glycogenes by butyrate, tricostatin A, and 5-aza-2'-deoxycytidine.
AB  - Cytomegalovirus (CMV) immediate early promoter is a powerful promoter frequently
      used for driving the expression of transgenes in mammalian cells. However, this
      promoter gradually becomes silenced in stably transfected cells. We employed
      Chinese Hamster Ovary (CHO) and human pancreatic cancer (Panc 1) cells stably
      tansfected with three glycogenes driven by a CMV promoter to study the activation
      of silenced glycogenes. We found that butyrate, tricostatin A (TSA), and 5-aza-2'
      deoxycytidine (5-Aza-dC) can activate these CMV-driven glycogenes. The increase
      in mRNA and protein of a glycogene occurred 8-10 h after butyrate treatment,
      suggesting an indirect effect of butyrate in the activation of the transgene. The
      enhanced expression of the trangenes by butyrate and TSA, known inhibitors of
      histone deacetylase, was independent of the transgene or cell type. However, the
      transgene can be activated by these two agents in only a fraction of the cells
      derived from a single clone, suggesting that inactivation of histone deacetylase
      can only partially explain silencing of the transgenes. Combination treatment of
      one or both agents with 5-Aza-dC, a known inhibitor of DNA methylase, resulted in
      a synergistic activation of the transgene, suggesting a cross-talk between
      histone acetylation and DNA demethylation. Understanding the mechanisms of the
      inactivation and reactivation of CMV promoter-controlled transgenes should help
      develop an effective strategy to fully activate the CMV promoter-controlled
      therapeutic genes silenced by the host cells.

PMID- 15864437
TI  - Biochemical characterization of Silene alba alpha4-fucosyltransferase and Lewis a
      products.
AB  - alpha1,4-Fucosylation has been recently detected in Arabidopsis thaliana [Leonard
      et al. (2002), Glycobiology 12: 299-306], and corresponding enzymes have also
      been characterized in Beta vulgaris [Bakker et al. (2001), FEBS Lett, 507: 307
      312], and Lycopersicum aesculentum [Wilson (2001), Glycoconjugate J., 18: 439
      447]. Here we demonstrated fucosyltransferase activity (FucT) in Silene alba
      cells and tissues. The Fuc linkage to GlcNAc residues of the lactosamine moiety
      of the Type I acceptor was confirmed by mass spectrometry experiments. Le(a)
      glycoconjugates are found in the Golgi apparatus and plasma membrane of plant
      cells. In planta, the highest levels of activity were detected in seedlings,
      young roots and male flowers. The enzyme was stable up to 45( composite
      function)C and the optimum pH of reaction was 8.0. The enzyme required Mg(2+) or
      Mn(2+) for activity and was inhibited by Zn(2+) and ethylenediaminetetraacetic
      acid. Chemical modification of the enzyme with group-selective reagents revealed
      that selective modifications of arginine and lysine residues had no effect on
      enzyme activity. However the enzyme contains histidine and tryptophan residues
      that are essential for its activity. In contrast to human FUT3, the S. alba
      alpha4-FucT was insensitive to N-ethylmaleimide (NEM) treatment. Measurement of
      enzyme activity in S. alba cell fractions indicated that the enzyme is bound to
      microsomal membranes, furthermore a soluble isoform of the protein may be
      present.

PMID- 15864439
TI  - Drosophila soluble guanylyl cyclase mutants exhibit increased foraging
      locomotion: behavioral and genomic investigations.
AB  - Genetic variation in the gene foraging (for) is associated with a natural
      behavioral dimorphism in the fruit fly, Drosophila melanogaster. Some larvae,
      called 'rovers', have increased foraging locomotion compared to others, called
      'sitters', and this difference is directly related to for-encoded cGMP-dependent
      protein kinase (PKG) activity. Here we report that larvae with mutations in the
      gene dgcalpha1, which encodes a soluble guanylyl cyclase (sGC) subunit, have
      increases in both PKG activity and foraging locomotion. This is contrary to our
      original prediction that, based on the role of sGC in the synthesis of cGMP,
      dgcalpha1 mutant larvae would have deficient cGMP production leading to decreased
      PKG activation and thus reduced larval foraging locomotion. We performed DNA
      microarray analyses to compare transcriptional changes induced by a dgcalpha1
      mutation in both rover and sitter wildtype genetic backgrounds. In either
      background, we identified many genes that are differentially transcribed, and
      interestingly, relatively few are affected in both backgrounds. Furthermore,
      several of these commonly affected genes are enhanced or suppressed in a
      background-dependent manner. Thus, genetic background has a critical influence on
      the molecular effects of this mutation. These findings will support future
      investigations of Drosophila foraging behavior.

PMID- 15864440
TI  - Experimental manipulation of sexual selection and the evolution of courtship song
      in Drosophila pseudoobscura.
AB  - Courtship song serves as a sexual signal and may contribute to reproductive
      isolation between closely related species. Using lines of Drosophila
      pseudoobscura experimentally selected under different sexual selection regimes,
      we tested whether increased promiscuity and enforced monogamy led to evolutionary
      changes in courtship song elements. In D. pseudoobscura, males produce both a low
      and high rate repetition song. We found that both song types diverged after
      selection and that the direction of changes was consistent with ordered
      hypotheses of predicted directions of change under the different mating system
      structures. In particular, latency to the initiation of song and duration of the
      interpulse interval (IPI) decreased in highly promiscuous lines and increased in
      monogamous lines. These results suggest that courtship song may rapidly evolve
      under different mating system structures, representing either functional
      evolution of more stimulatory song under conditions of strong sexual selection,
      or might result from increased courtship vigor, or represent correlated
      evolution. Some speciation theory predicts that increased sexual selection should
      result in increased variance of traits between allopatric populations,
      facilitating reproductive isolation. We also found that courtship song elements
      were not equally variable between replicate lines.

PMID- 15864441
TI  - The role of male courtship song in species recognition in Drosophila montana.
AB  - In many Drosophila species the male courtship song is an essential part of a
      successful courtship, playing a role in species-recognition and/or in sexual
      selection exercised by the females on conspecific males. In Drosophila montana,
      specific traits of the courtship song (the length and the carrier frequency of
      sound pulses) have earlier been shown to play an important role in intraspecific
      mate choice. Here we show that the male song (especially the interpulse interval)
      also plays a role in species-recognition, maintaining sexual isolation between
      sympatric species. We succeeded in breaking down sexual isolation between D.
      montana females and D. lummei males by playing the females simulated courtship
      song with a species-specific interpulse interval while they were courted by a
      mute (wingless) male. Involvement of different song traits in intra- and
      interspecific mate choice suggests that the song may be affected by both
      directional and stabilizing selection.

PMID- 15864442
TI  - Mutations and natural genetic variation in the courtship song of Drosophila.
AB  - All Drosophila species have a courtship repertoire by which a male stimulates a
      female to mate with him. In many species, males vibrate their wings to produce
      courtship song, an element of courtship that plays an important role in female
      choice. Each species has a unique courtship song, with the major differences
      among species songs being in timing and/or structure. Analysis of genetic
      mutations has revealed 17 genes that affect courtship song in Drosophila
      melanogaster. Most of the genes were first identified as affecting another trait
      and were subsequently shown to affect song. Quantitative genetic studies have
      demonstrated a polygenetic additive genetic architecture for many song traits.
      Few candidate genes, identified through the classical genetic approach, coincide
      with the regions implicated as affecting natural variation. With many new tools
      in genetic analysis and the multiple Drosophila genome projects currently
      underway, the ability to relate mutational and quantitative analyses will
      improve.

PMID- 15864443
TI  - Cuticular hydrocarbons: their evolution and roles in Drosophila pheromonal
      communication.
AB  - I review the recent literature on cuticular hydrocarbons (CHs) in Drosophila.
      First, the major structural features of CHs are examined in a variety of species
      with regard to phylogeny. The genetic bases of the CH variation between and
      within species have been investigated with some of the genes involved
      characterized and manipulated. The effect of non-genetic factors as temperature,
      food and development is also examined with regard to CH production. Using a model
      involving the stimulating or the inhibiting role of CHs, it is possible to
      speculate on the mechanisms of CH perception and on the role(s) that these
      substances could play on sexual isolation and on the evolution of pheromonal
      communication.

PMID- 15864444
TI  - Sexual selection and speciation in hawaiian Drosophila.
AB  - Many ideas about sexual selection and speciation have been stimulated by
      considering Hawaiian Drosophila. In turn, the ideas and models have stimulated
      research with the flies, particularly members of the planitibia group. This paper
      describes high points of some of the models and reviews data that are relevant to
      understanding sexual selection and speciation in this species group.

PMID- 15864445
TI  - Sexual isolation between sympatric and allopatric populations of Drosophila
      pseudoobscura and D. persimilis.
AB  - According to reinforcement theory, sexual isolation between species in sympatry
      is strengthened by natural selection against maladaptive hybrids. Drosophila
      pseudoobscura and D. persimilis from four locations where these species are
      sympatric, and from three locations where only D. pseudoobscura has been found,
      were utilized in studies of sexual isolation. Multiple-choice observation
      chambers were used to record matings between sympatric and allopatric strains of
      the two species. There was a wide variation in sexual isolation between the two
      species in the four localities we studied. The average isolation index for
      sympatric strains of the species was not significantly different from the average
      index for allopatric strains. There were no meaningful differences between the
      isolation indices in sympatric and allopatric strains of the species. The failure
      to find a relationship is likely the result of gene flow among populations within
      the two species.

PMID- 15864446
TI  - Use of repeated measures to interpret genetic and environmental correlations in
      animal research.
AB  - A method for partitioning environmental correlations into two distinct sources of
      covariation--lifetime rearing effects and idiosyncratic stimulus events occurring
      during testing ("noise")--is presented. The method, which is based on structural
      equation modeling of repeated tests, is demonstrated using correlations obtained
      from pairs of sessions in an Open Field Test and in a Light-Dark Test.
      Heritabilities of most behaviors are low, but genetic correlations between- and
      within-test sessions are high and thus substantively influence phenotypic
      correlations, including test-retest reliability. Testing "noise" is usually the
      primary source of environmental covariance among pairs of measures, although some
      instances of rearing environment being the sole source of E correlations were
      observed. Effects of Session 1 testing and/or the additional experience between
      S1 and S2 test sessions produce some significant differences between S1 and S2
      within-session correlations, but these are usually not large. Although varying in
      size, the genetic, the rearing environment and the test environment correlations
      between a pair of variables were always consistent in sign. The analysis
      demonstrates the value of incorporating some of the contemporary research and
      analytic strategies used in the human individual differences field into animal
      studies.

PMID- 15864447
TI  - Use of a standard strain for external calibration in behavioral phenotyping.
AB  - The present paper evaluates the inclusion of a standard strain or outbred stock
      in multi-strain behavioral phenotyping protocols to perform the same role as the
      external standard in biochemical assay procedures. As potential standards, the
      F344 inbred strain and an outbred stock of Long Evans were tested with three
      other inbred strains. To evaluate the influence of rearing conditions on
      phenotype stability, one group of F344s was born at the University of Tsukuba,
      another, bred elsewhere and delivered to Tsukuba at 4 weeks of age. All animals
      were tested in open-field (OF), runway emergence (RE) and digging tests as
      adults. The results showed no influence of breeding or transportation history on
      OF and RE behavior of the two F344 groups, while there was evidence that digging
      behavior may be affected by the different rearing experience. The inclusion of a
      'standard strain or stock' in phenotyping protocols involving multiple inbred
      strains or lines of rats, mice and flies has obvious advantages by providing a
      reference point for inter-laboratory comparisons. The properties of inbred
      strains and outbred stocks favorable to their use as standards are discussed.

PMID- 15864448
TI  - Functional analysis of genes implicated in Down syndrome: 2. Laterality and
      corpus callosum size in mice transpolygenic for Down syndrome chromosomal region 
      1 (DCR-1).
AB  - The association between atypical laterality and mental retardation has been
      reported several times, particularly in Down syndrome (DS). We investigated
      common genetic correlates of these components of the syndrome, examining
      direction (number of right paw entries in the Collins test) and degree (absolute
      difference between the number of right paw entries and the number of left paw
      entries) in mice that had incorporated extra-contiguous HSA21 fragments covering
      DCR-1 (Down Chromosomal Region-1). As corpus callosum size is substantially
      reduced in DS, and as the structure has been suspected of playing a role in
      atypical laterality, we also measured the corpus callosum in these mice. Extra
      copies of two regions (F7 and E6) have been associated with an atypical degree of
      laterality (strongly reduced degree). Extra copies of E8, G6 and E6 are also
      linked to the reduced size of the corpus callosum, indicating that the abnormal
      number of fibers linking the two hemispheres is not associated with atypical
      laterality in DS. Together, these results indicate that some of the genes
      involved in atypical laterality and in the reduced size of the corpus callosum in
      DS are present on DCR-1. An extra copy of F7 and, to a lesser extent, an extra
      copy of E6, are also associated with cognitive impairment. These results support
      the hypothesis of common genetic correlates in atypical laterality and mental
      retardation in DS.

PMID- 15864449
TI  - On the other hand.
AB  - This paper presents a brief overview of the past and current state of handedness
      research illustrating some of the controversies. It emphasizes two aspects: the
      lack of agreement on the behavior that indicates to which hand-use group (left or
      right) an individual belongs, and the reasons for preferring one hand rather than
      the other for various manual activities.

PMID- 15864450
TI  - Handedness in children of schizophrenic parents: data from three high-risk
      studies.
AB  - This is the first report of data analyses from a consortium of longitudinal
      genetic-risk studies on offspring of schizophrenic parents (CLOSSER) who were
      followed from birth or mid-childhood to their early 20's or considerably older
      ages. Three of the CLOSSER studies provide data to enable us to address long
      persisting questions in the schizophrenia literature concerning possible
      atypicality of hand dominance associated with the illness. Handedness, used as a
      proxy for cerebral lateralization, is a topic of considerable importance because
      of its potential to reveal mechanisms in the underlying pathophysiology of
      schizophrenia. We examine agreement among the CLOSSER studies with respect to
      possible deviance in handedness in subjects with schizophrenic parents (high-risk
      individuals) and specifically in those who have gone on to develop adult
      schizophrenia, compared with other subjects of these studies. Possible
      developmental delay in age at lateralization is also considered.

PMID- 15864451
TI  - Testosterone and alcohol use among adolescent male twins: testing between-family
      associations in within-family comparisons.
AB  - We examined associations of testosterone (T) and alcohol use in adolescent twin
      brothers, conducting both between- and within-family analyses. The twins
      completed semi-structured interviews, provided two saliva samples to assay T, and
      reported their drinking patterns and pubertal development. We adjusted T levels
      for diurnal/seasonal effects and association with pubertal maturation. In
      analyses of twins as individuals, higher T levels characterized boys reporting
      ever drinking, more frequent intoxication, high density drinking, more alcohol
      symptoms, and diagnosed alcohol dependency on interview. Adjusting for pubertal
      development, only associations with symptom count and diagnosis remained
      significant. The association with frequent intoxication replicated among drinking
      discordant twin brothers, effectively ruling out between-family confounds, but
      that association was not significant after adjustment for pubertal development.
      The phenotypic correlation between T and pubertal maturation is largely genetic,
      inviting study of the magnitude and meaning of linkages between testosterone and
      symptoms of alcoholism on follow-up in early adulthood.

PMID- 15864453
TI  - Gyrodactylus pictae n. sp. (Monogenea: Gyrodactylidae) from the Trinidadian swamp
      guppy Poecilia picta Regan, with a discussion on species of Gyrodactylus von
      Nordmann, 1832 and their poeciliid hosts.
AB  - Gyrodactylus pictae n. sp. is recorded from Poecilia picta in heterospecific
      shoals with the guppy P. reticulata in Northern Trinidad. G. pictae is
      morphologically similar to G. turnbulli Harris, 1986, but the hamuli and marginal
      hooks are slightly smaller and more gracile. The toe and the point of the
      marginal hook have a distinctly different shape, providing the best morphological
      characters for distinguishing the two species. The rDNA ITS1 and ITS2 sequences
      differ from those of G. turnbulli (the closest relative) by >5, suggesting that
      these two taxa are not sibling species. The origin of the two species on
      poeciliids of the subgenus Micropoecilia is discussed, and it is suggested that
      this may represent a case of host-parasite co-evolution.

PMID- 15864454
TI  - Gyrodactylus thlapi n. sp. (Monogenea) from Pseudocrenilabrus philander philander
      (Weber) (Cichlidae) in the Okavango Delta, Botswana.
AB  - A new species of Gyrodactylus von Nordmann, 1832 and the first monogenean
      reported from Botswana is described from the cichlid Pseudocrenilabrus philander
      philander, bringing the number of gyrodactylids described from the African
      Continent to 18. Gyrodactylus thlapi n. sp. can be readily discriminated from the
      other described species almost exclusively by the shape of its hamuli, which have
      short roots and large, elongate ventral bar attachment points with the dorsal bar
      attachment point, demarcating the junction between the hamulus shaft and the
      root, positioned at the anterior terminus of the attachment plane. The marginal
      hooks of G. thlapi n. sp., which most closely resemble those of G. groschafti
      Ergens, 1973, are compared and discussed.

PMID- 15864455
TI  - Monocotylids (Monogenea: Monopisthocotylea) from Aetobatus cf. narinari off New
      Caledonia, with a description of Decacotyle elpora n. sp.
AB  - Four species of monocotylid monogeneans were found on a spotted eagle ray
      Aetobatus cf. narinari caught off Noumea, New Caledonia, South Pacific. The host
      is illustrated for future possible identification, because it belongs to a
      currently unresolved species complex. Decacotyle octona (Young, 1967) Chisholm &
      Whittington, 1998, from the secondary gill lamellae, is figured and previously
      unreported details of the reproductive system are described. D. elpora n. sp. is
      described from numerous specimens found between the secondary gill lamellae. The
      new species, 780-1650 microm in body length, is smaller than D. octona, but has a
      longer sclerotised male copulatory organ. It is characterised by two dorsal
      haptoral accessory structures, each with three bumps, and a 9-shaped sclerotised
      male copulatory organ 240-290 microm in length. D. octona and Clemacotyle
      australis Young, 1967, both from the branchial cavity, and Thaumatocotyle
      pseudodasybatis Hargis, 1955, from the nasal tissue, are new geographical records
      for New Caledonia. It is suggested that differences in the monocotylid fauna
      between the Atlantic and Indo-Pacific forms of Aetobatus cf. narinari could be of
      interest for the systematic status of the ray, but the sporadic nature of the
      sampling probably casts doubt on the usefulness of the currently available data.

PMID- 15864456
TI  - [In progress citation].
AB  - During a study of the gill parasites (Monogenea) of two species of Diplodus
      Rafinesque (Sparidae), D. sargus (Linnaeus) and D. vulgaris (Geoffroy Saint
      Hilaire) from off the Algerian coast, several species of the family Diplectanidae
      Bychowsky, 1957 and genus Lamellodiscus Johnston & Tiegs, 1922 were collected. We
      present a redescription of L. ergensi Euzet & Oliver, 1966 and describe two new
      species, L. kechemirae n. sp. and L. tomentosus n. sp. These new species are
      close to L. ergensi but differ in the morphology and size of both the haptoral
      sclerites and the male genital system. On the basis of the dorsal lateral bars of
      the haptor, we suggest the recognition within the group 'ignoratus' of Oliver
      (1987) of two subgroups, 'ignoratus' (sensu stricto), with simple dorsal bars,
      and 'ergensi', with complex bars which are more or less divided in two parts. We
      also present a redescription of L. baeri Oliver, 1974, collected from the sparid
      Pagrus pagrus (Linnaeus) (the type-host) and allocate it to the 'ergensi'
      subgroup. All of these species of Lamellodiscus are reported from sparids off the
      Algerian coasts for the first time.

PMID- 15864457
TI  - Two new hemiurine species (Digenea: Hemiuridae) from Spratelloides robustus
      Ogilby (Clupeiformes: Clupeidae) off south-western Australia and records of
      Parahemiurus merus (Linton, 1910) from Australian and New Caledonian waters.
AB  - Two new species of hemiurine hemiurid are described from Spratelloides robustus
      off Woodman Point in southern Western Australia. Hemiurus lignator n. sp. differs
      from its congeners by a combination of similar-sized suckers, long sinus-sac,
      tandem testes, relatively elongate shape and unthickened seminal vesicle wall.
      Parahemiurus xylokopos n. sp. differs from its congeners in a combination of its
      squat form, its distinctly lobed vitellarium and the proximity of the gonads to
      the ventral sucker. P. merus (Linton, 1910) is reported from Acanthopagrus
      australis, Pomatomus saltatrix and Trachinotus coppingeri off northern New South
      Wales, Caranx sexfasciatus, Scorpis lineolata, Siganus nebulosus, Thunnus tonggol
      and T. coppingeri off southern Queensland, Cephalopholis boenak and Euthynnus
      affinis off Heron Island, southern Great Barrier Reef, P. saltatrix off southern
      Western Australia and Priacanthus hamrur off New Caledonia.

PMID- 15864458
TI  - Atactorhynchus duranguensis n. sp. (Acanthocephala: Atactorhynchinae) from
      Cyprinodon meeki (Pisces: Cyprinodontidae) near Durango, Mexico.
AB  - Atactorhynchus duranguensis n. sp. (Acanthocephala: Atactorhynchinae) is
      described from the intestine of Cyprinodon meeki Miller, an endemic freshwater
      fish from a far-inland locality of Mexico. Diagnostic features include: body
      small, stout, ventrally curved; small cylindrical proboscis armed with 16
      alternating vertical rows of four or five hooks; anterior two or three hooks
      conspicuous, stout and larger than other hooks, and have large, rod-shaped roots
      with a markedly and abruptly enlarged base; three posterior hooks of each row are
      smaller and rootless; single-walled proboscis receptacle; lemnisci equal in
      length, elongate and robust; and cement gland syncytial, larger than testis. The
      new species is smaller than A. verecundus Chandler, 1935, the only previously
      described species in the genus. The shape of the proboscis of the new species is
      strikingly different from that of A. verecundus, which is widest at the apex.
      Likewise, the greatest width of the trunk of the new species is in about the
      middle, differing from that of A. verecundus where the trunk is widest
      posteriorly. The new species also can be distinguished from A. verecundus because
      of its much smaller hook lengths and slightly smaller proboscis. In addition, the
      proportion of large apical proboscis hooks in relation to the small basal hooks
      is different: the basal hooks of A. verecundus are about half the size of the
      anterior hooks and but only about a quarter of the size in A. duranguensis.
      Unlike A. verecundus, the base of the roots are markedly and abruptly enlarged in
      the new species. Finally, the eggs of the new species are smaller (23-27 x 8-10
      microm) than those of A. verecundus (27-30 x 12-13 microm).

PMID- 15864459
TI  - Three new genera of trypanorhynch cestodes from Australian elasmobranch fishes.
AB  - Three new genera of trypanorhynch cestodes from Australian elasmobranch fishes
      collected in the Arafura Sea, off the Northern Territory, are described.
      Fossobothrium perplexum n. g., n. sp. (Otobothriidae), from the spiral valves of
      Anoxypristis cuspidata (Latham) and Pristis zijsron Bleeker, is similar to the
      otobothriid genera Pseudotobothrium Dollfus, 1942 and Poecilancistrium Dollfus,
      1929 in possessing bothrial pits and a band of hooks on the tentacle, but differs
      from all known otobothriid genera in having the pits joined by a prominent velum.
      Iobothrium elegans n. g., n. sp. (Otobothriidae), from the spiral valve of
      Himantura jenkinsi (Annandale), is placed in the Otobothriidae because it
      possesses bothrial pits, but differs from Otobothrium Linton, 1890 and other
      genera in lacking intercalary hooks between the principal rows and in possessing
      a chainette on the external surface of the tentacle in the metabasal region.
      Oncomegoides celatus n. g., n. sp. (Eutetrarhynchidae), from the spiral valve of
      Dasyatis microps (Annandale) and Himantura jenkinsi, resembles Oncomegas Dollfus,
      1929 in possessing two bothria and a megahook on the bothrial surface of the
      basal armature, but differs in possessing an extra row consisting of four
      intercalary hooks formed by the overlapping of two intercalary hooks on the
      external tentacular surface between each of the opposing principal rows and is
      therefore an atypical heteroacanth.

PMID- 15864460
TI  - Ixodes (Ixodes) pararicinus Keirans & Clifford, 1985 (Acari: Ixodidae):
      description of the immature stages, distribution, hosts and medical/veterinary
      importance.
AB  - The immature stages of the Neotropical tick Ixodes (Ixodes) pararicinus Keirans &
      Clifford, 1985 are described from specimens in a laboratory colony initiated from
      engorged females collected on cattle and larvae fed on mice and chickens. The
      larva and nymph of I. pararicinus are described using SEM micrographs as well as
      drawings for some features of the larva. Additionally, immature stages of I.
      pararicinus collected on wild mice and birds in Uruguay and Argentina were
      compared with specimens from the laboratory colony. A taxonomic key to the nymphs
      of the species of the ricinus complex established in the Western Hemisphere is
      presented. The distribution of I. pararicinus comprises Argentina, Colombia and
      Uruguay, but it is also probably established in Bolivia, Brazil, Chile and Peru.
      Most adult ticks of this species have been found on introduced domestic
      artiodactyles, although Neotropical deer species must have been the ancestral
      host. Larvae and nymphs of I. pararicinus have also been found on sigmodontine
      rodents and passeriform birds. Although I. pararicinus is a member of the ricinus
      complex, which contains the main vectors of Borrelia burgdorferi (sensu lato),
      there are few studies concerning its potential for pathogen transmission.

PMID- 15864461
TI  - Profile: Herman Lent (1911-2004).

PMID- 15864465
TI  - Sensible and latent heat loss from the body surface of Holstein cows in a
      tropical environment.
AB  - The general principles of the mechanisms of heat transfer are well known, but
      knowledge of the transition between evaporative and non-evaporative heat loss by
      Holstein cows in field conditions must be improved, especially for low-latitude
      environments. With this aim 15 Holstein cows managed in open pasture were
      observed in a tropical region. The latent heat loss from the body surface of the
      animals was measured by means of a ventilated capsule, while convective heat
      transfer was estimated by the theory of convection from a horizontal cylinder and
      by the long-wave radiation exchange based on the Stefan-Boltzmann law. When the
      air temperature was between 10 and 36 degrees C the sensible heat transfer varied
      from 160 to -30 W m(-2), while the latent heat loss by cutaneous evaporation
      increased from 30 to 350 W m(-2). Heat loss by cutaneous evaporation accounted
      for 20-30% of the total heat loss when air temperatures ranged from 10 to 20
      degrees C. At air temperatures >30 degrees C cutaneous evaporation becomes the
      main avenue of heat loss, accounting for approximately 85% of the total heat
      loss, while the rest is lost by respiratory evaporation.

PMID- 15864466
TI  - Genetic studies of osteoporosis--a rethink required.

PMID- 15864467
TI  - Umbilical cord leptin predicts neonatal bone mass.
AB  - Evidence is accumulating that the risk of osteoporosis in later life may be
      determined in part by environmental influences on bone development during
      intrauterine and early postnatal life. A potential role for fetal leptin in
      mediating these effects is suggested by animal studies showing that leptin
      influences prenatal osteoblast growth and development, and that fetal leptin
      concentrations are altered by changes in maternal nutrition. In a group of term
      human infants we reported previously that maternal birthweight, smoking, fat
      mass, and exercise during late pregnancy independently predict neonatal bone
      mass. To investigate the potential role of leptin in mediating these effects, we
      now relate leptin concentrations in umbilical venous serum to neonatal bone mass
      and body composition in 117 infants. There were strong positive associations
      between umbilical venous leptin concentration and each of whole body bone mineral
      contents (BMC) (r = 0.42, P < or = 0.001) and estimated volumetric bone density
      (r = 0.21, P = 0.02); whole body lean mass (r = 0.21, P < or = 0.024); and whole
      body fat mass (r = 0.60, P < 0.001). The associations with neonatal BMC and fat
      mass, but not with lean mass, were independent of associations that we have
      reported previously between cord serum insulin-like growth factor 1 (IGF-1)
      concentrations and neonatal body composition. Among the maternal determinants of
      neonatal bone mass, cord leptin explained the relationship with maternal fat
      stores, but not those with the mother's own birthweight, smoking, or physical
      activity. We conclude that umbilical venous leptin predicts both the size of the
      neonatal skeleton and its estimated volumetric mineral density. In addition,
      among previously documented maternal determinants of neonatal bone mass in
      healthy pregnancies, maternal fat stores may mediate their effect on fetal bone
      accrual through variation in fetal leptin concentrations.

PMID- 15864468
TI  - Fishing for answers with transposons.
AB  - Transposons are one means that nature has used to introduce new genetic material
      into chromosomes of organisms from every kingdom. They have been extensively used
      in prokaryotic and lower eukaryotic systems, but until recently there was no
      transposon that had significant activity in vertebrates. The Sleeping Beauty (SB)
      transposon system was developed to direct the integration of precise DNA
      sequences into chromosomes. The SB system was derived from salmonid sequences
      that had been inactive for more than 10 million years. SB transposons have been
      used for two principle uses--as a vector for transgenesis and as a method for
      introducing various trap vectors into (gene-trap) or in the neighborhood of
      (enhancer-trap) genes to identify their functions. Results of these studies show
      that SB-mediated transgenesis is more efficient than that by injection of simple
      plasmids and that expression of transgenesis is stable and reliable following
      passage through the germline.

PMID- 15864469
TI  - Genetic evidence of postglacial population expansion in Puget Sound rockfish
      (Sebastes emphaeus).
AB  - Several rockfish species (genus Sebastes) along the northeastern Pacific Ocean
      have rapidly declined in abundance owing in part to overfishing. A striking
      exception is the dwarf-like Puget Sound rockfish Sebastes emphaeus, whose
      densities have increased by several orders of magnitude over the last several
      decades. To describe their genetic structure, we sequenced 395 bp from the
      mitochondrial control region of 128 S. emphaeus adults from 5 locations spanning
      approximately 120 km of the Northwest Straits of Washington state. We detected no
      significant genetic differentiation among these populations and substantial
      genetic variation within populations, a pattern that may indicate high levels of
      ongoing gene flow. Preliminary data from 2 microsatellite loci are also
      consistent with panmixia. The mtDNA sequences also suggest that Puget Sound
      rockfish populations have expanded substantially since the retreat of Pleistocene
      glaciers made habitat in Puget Sound region available approximately 12,000 years
      ago.

PMID- 15864470
TI  - Induction of Japanese flounder tnf promoter activity by lipopolysaccharide in
      zebrafish embryo.
AB  - A recombinant plasmid containing the 2381-bp promoter region of Japanese flounder
      tumor necrosis factor (TNF) and green fluorescence protein (GFP) was introduced
      into zebrafish fertilized eggs by microinjection. GFP was expressed in 2
      transgenic zebrafish lines in the heart and around the pharynx under unstressed
      condition. When embryos were exposed to lipopolysaccharide (LPS), GFP was
      expressed in the whole zebrafish embryonic surface, and Western blot analysis
      also showed that the level of the expressed GFP protein in zebrafish embryo was
      higher at an LPS concentration of 140 microg/ml than at LPS concentrations of 0
      and 70 microg/ml. Stimulation with either concanavalin A or phorbol myristate
      acetate induced weak GFP expression, but stimulation with both of them induced
      strong expression similar to that induced by LPS. GFP expression peaked 1 hour
      after stimulation, then gradually decreased. These results indicate that
      transcription regulated by the Japanese flounder TNF promoter could be under the
      control of the LPS-recognition system in zebrafish embryos.

PMID- 15864472
TI  - Improving small-diameter vascular grafts: from the application of an endothelial
      cell lining to the construction of a tissue-engineered blood vessel.
AB  - One of the main reasons why vascular reconstruction with synthetic small-diameter
      grafts has limited success is the absence of endothelial cells. To improve the
      outcome of nonvenous vascular bypass surgery, cell seeding of vascular grafts and
      other tissue-engineering techniques were developed. In this article, an overview
      is given of the artificial blood vessel as an alternative for venous vascular
      bypass surgery.

PMID- 15864473
TI  - The prophylactic use of inferior vena cava filters in patients undergoing high
      risk spinal surgery.
AB  - Prophylactic inferior vena cava filter (IVCF) placement is advocated in some high
      risk groups. We sought data regarding safety and efficacy for prophylactic IVCF
      placement in patients at high risk for venous thromboembolism (VTE) following
      major spinal reconstruction. Seventy-four spine surgery patients with
      contraindication to anticoagulation (44 females, 30 males; mean age 56.2)
      received prophylactic IVCFs. Criteria were (1) history of thromboembolism, (2)
      diagnosed thrombophilia, (3) malignancy, (4) bedridden >2 weeks prior to surgery,
      (5) staged procedures or multiple levels, (6) combined anterior/posterior
      approaches, (7) expected need for significant iliocaval manipulation during
      exposure, and (8) single-stage anesthetic time >8 hr. Seventy patients had at
      least two risk factors. All received IVCFs prior to the first stage of spine
      reconstruction. Patients were evaluated for filter complications, deep vein
      thrombosis (DVT), and pulmonary embolism (PE). Patients' lower extremity veins
      from groin to ankle were imaged weekly until discharge using duplex ultrasound
      (DUS). One-third also underwent thoracic and pelvic computed tomography scans,
      and the pelvic veins, IVC, and pulmonary vasculature were evaluated for VTE.
      Multiple DUS (n = 198, mean 2.6 studies per patient) were performed in 68
      patients. At a mean follow-up of 11 months, one of the patients developed PE.
      Twenty-seven limbs in 23 patients developed DVT. Five limbs had isolated calf
      DVT, and 22 had proximal vein involvement. Insertion site DVT accounted for
      nearly one-third of the DVTs. Six patients died from unrelated complications.
      There was one technical error with an IVCF deployed in the iliac vein. Despite a
      high incidence of DVT following high-risk spinal surgery, prophylactic IVCF
      placement appears to protect patients from PE.

PMID- 15864471
TI  - Small metallothionein MT-10 genes in coastal and hydrothermal mussels.
AB  - Metallothioneins (MTs) are important proteins in the intracellular regulation of
      metals. In the Mytilidae family, which includes many economically important
      species, 2 major forms of MTs have been reported: MT-10 (10 kDa) and MT-20 (20
      kDa). Many different MT-10 proteins have been isolated from the common species
      Mytilus edulis, which suggests that distinct MT-10 genes may occur in a single
      specimen. Some MT genes, involving 3 exons and 2 large introns, have been
      isolated in Mytilidae. Our aim was to determine whether intron-free forms of the
      MT-10 genes can exist, which could allow rapid transcription in response to
      exposure to metals. Our study focused on 2 species living under very different
      environmental conditions: Mytilus edulis (a coastal mussel) and Bathymodiolus
      thermophilus (a hydrothermal mussel). We report here the first description of
      small, intron-free MT-10 genes, possessing a correct open reading frame in these
      2 species.

PMID- 15864474
TI  - Endovascular stent graft repair of a persistent sciatic artery aneurysm.
AB  - An 88-year-old female presented with a large, painful, pulsatile buttock mass.
      Computed tomographic angiogram with three-dimensional reconstruction and lower
      extremity arteriogram revealed a 5 cm sciatic artery aneurysm. We report a case
      of successful repair of a sciatic artery aneurysm with endovascular stent graft.

PMID- 15864475
TI  - Intraarterial thrombolysis and stent placement in the acute phase of blunt
      internal carotid artery trauma with subocclusive dissection and thromboembolic
      complication: case report and review of the literature.
AB  - The case of a patient with blunt traumatic internal carotid artery dissection
      associated with subocclusive stenosis and thromoboembolic complication is
      presented. The patient suffered fluctuant neurological abnormalities and several
      open and closed fractures of the left limb. The vascular lesion and its
      complication were successfully treated with intraarterial thrombolysis and stent
      placement during the acute phase, prior to the open surgical treatment of the
      fractures.

PMID- 15864476
TI  - Paravertebral pseudoaneurysm thrombosed after percutaneous thrombin injection.
AB  - We present a case of a lumbar pseudoaneurysm in a 62-year-old patient with
      myelofibrosis (agnogenic myeloid metaplasia). The patient was submitted to two
      anesthetic infiltrations for lumbar pain and one biopsy of a suspected
      hematopoietic site. Subsequently, a 4.5 cm lumbar pseudoaneurysm was diagnosed.
      The pseudoaneurysm was thrombosed with 1 ml (500 IU) thrombin injection with a
      successful clinical result. We discuss different treatment options along with
      several issues related to the most frequent complication of this technique,
      namely, native artery thrombosis.

PMID- 15864477
TI  - Blunt handlebar injury of the common femoral artery: a case report.
AB  - Bicycle handlebar-related blunt trauma to the femoral vessels with resulting
      arterial injury has been described previously. However, significant injury to the
      ileofemoral tree with underlying arterial occlusive disease in the face of
      handlebar-related trauma has not been reported. We present the case of an all
      terrain vehicle accident with isolated injury to the common femoral artery in a
      patient with underlying atherosclerotic disease.

PMID- 15864478
TI  - Static mechanical properties of custom-made aortic endografts.
AB  - Several cases of delayed aortic rupture after endovascular aneurysm repair have
      been attributed to in vivo endograft fatigue. Such complications could involve
      damage to structural components during introduction. The purpose of this study
      was to compare forces applied during introduction to forces needed to damage the
      endograft. Testing was carried out on the custom-made endograft (CMEG) that has
      been in almost exclusive use at our center since 1996. Findings showed that the
      force applied during introduction was less than the force necessary to damage the
      endograft. No alteration in the mechanical properties of the CMEG was observed
      immediately after implantation.

PMID- 15864479
TI  - Infragenicular bypass graft for limb salvage using polytetrafluoroethylene and
      distal vein cuff as the first alternative in patients without ipsilateral greater
      saphenous vein.
AB  - The objectives of this study were to evaluate the results of
      polytetrafluoroethylene infragenicular bypass grafts with a distal interposition
      vein cuff in patients with critical limb ischemia in the absence of ipsilateral
      greater saphenous vein. From January 1997 to June 2002, 58 consecutive below-knee
      bypass grafts with PTFE and distal interposition vein cuff were performed in 57
      patients with a median age of 70.8 years. The distal anastomosis was located at
      the infragenicular popliteal artery in 18 cases and at tibial vessels in 40.
      Primary patency, secondary patency, and limb salvage were analyzed using the
      Kaplan-Meier method. During a median follow-up of 14.4 months (range, 1-50) 26
      cases of graft occlusion and 19 major amputations were registered. The primary
      and secondary patency rates at 12, 24, and 36 months were 57%, 54%, and 47% and
      61%, 58%, and 50%, respectively. Limb salvage rates reached 69%, 69%, and 59% at
      12, 24, and 36 months. When below-knee revasculanzation is required in patients
      with limb-threatening ischemia, in the absence ipsilateral greater saphenous
      vein, PTFE grafts with a distal vein cuff are a reasonable substitute with
      acceptable long-term patency and limb salvage rates.

PMID- 15864480
TI  - Correlation between concordance of tracers, order of harvest, and presence of
      metastases in sentinel lymph nodes with breast cancer.
AB  - BACKGROUND: There are various methods for the detection of sentinel lymph nodes
      (SLNs) in breast cancer by using a combined method with blue dye and radioisotope
      (RI) tracers. The purpose of the study was to reveal any correlation between
      concordance of the tracers and the order of harvest with the presence of
      metastases in SLNs. METHODS: The outcomes were reviewed in 408 cases with stage 0
      to II breast cancer; the combined method was used in which blue dye and RI were
      injected subcutaneously around the tumor. The radioactivity and blue staining in
      each harvested SLN were checked. RESULTS: In 330 cases (81%), SLNs contained both
      blue dye and RI tracers (blue-hot cases), and in 42 (10%) and 31 (8%) cases, the
      SLNs contained only the blue stain (blue-only cases) and only RI (hot-only
      cases), respectively. The overall metastatic rate was 25% on a patient basis.
      Blue-only cases had a higher rate (42%) of metastasis than hot-only cases (14%).
      The rate of nodes containing both blue dye and RI gradually decreased from the
      first SLNs harvested to the third SLNs harvested. The rate of nodes containing RI
      only increased with the number harvested, and there was not so much change in the
      rate of nodes containing blue only. CONCLUSIONS: These data suggest that RI
      tracer could detect a wide range of SLNs and that the blue dye tracer could
      efficiently detect SLNs with metastasis. The combined methods compensates for the
      deficiencies of each method and thus will probably help to prevent missing SLNs.

PMID- 15864481
TI  - Sentinel lymph node tumor load: an independent predictor of additional lymph node
      involvement and survival in melanoma.
AB  - BACKGROUND: Even though 60% to 80% of melanoma patients with a positive sentinel
      lymph node (SLN) have no positive additional lymph nodes (ALNs), all these
      patients are subjected to an ALN dissection (ALND) with its associated morbidity.
      The aim of this study was to predict the absence of ALN metastases in patients
      with a positive SLN by using features of the primary melanoma and SLN tumor load.
      METHODS: Of 71 SLN-positive patients, 52 had metastasis limited to the SLN (group
      1), and 19 had > or =1 positive ALN after ALND (group 2). The tumor load of the
      SLN was assessed by measuring the total surface area by computerized morphometry.
      Breslow thickness, ulceration and lymphatic invasion of the primary tumor, and
      total SLN metastatic area were tested as covariates predicting the absence of
      positive ALNs. RESULTS: The mean SLN metastatic area was 1.18 mm(2) (group 1) and
      3.39 mm(2) (group 2) (P = .003) and was the only significant and independent
      factor after multivariate analysis (P = .02). None of the patients with both a
      Breslow thickness <2.5 mm and an SLN metastatic area <.3 mm(2) had a positive
      ALN. CONCLUSIONS: SLN metastatic area can be used to predict the absence of
      positive ALNs in melanoma patients. In this study, patients with a Breslow
      thickness <2.5 mm and an SLN tumor load <.3 mm(2 )seemed to have no positive ALN
      and had excellent survival. We hypothesize that this subgroup might not benefit
      from ALND. Prospective larger trials, using this model and randomizing between
      ALND and no ALND, should confirm this hypothesis.

PMID- 15864482
TI  - Mitotic rate as a predictor of sentinel lymph node positivity in patients with
      thin melanomas.
AB  - BACKGROUND: Lymphatic mapping and sentinel lymphadenectomy (LM/SL) provide
      important prognostic information for patients with early-stage melanoma. Although
      the use of this technique in patients with thin melanomas (< or =1.00 mm) is not
      routine, risk factors that may predict sentinel lymph node (SLN) positivity in
      this patient population are under investigation. We sought to determine whether
      mitotic rate (MR) is associated with SLN positivity in thin-melanoma patients
      and, therefore, whether it may be used to risk-stratify and select patients for
      LM/SL. METHODS: Clinical and histopathologic variables were reviewed for 181
      patients with thin melanomas who underwent LM/SL from January 1996 through
      January 2004. Univariate and multivariate logistic regression analyses were
      performed to identify factors associated with SLN positivity. Risk groups were
      defined on the basis of the development of a classification tree. RESULTS: The
      overall SLN positivity rate was 5%. All patients with positive SLNs had an MR of
      >0. By univariate analysis, MR and thickness were significant predictors of SLN
      positivity. The association between MR and SLN positivity remained significant
      controlling for each of the other variables evaluated. On the basis of a
      classification tree, patients with an MR >0 and tumor thickness > or =.76 mm were
      identified as a higher-risk group, with an SLN positivity rate of 12.3%.
      CONCLUSIONS: In patients with thin melanomas, MR >0 seems to be a significant
      predictor of SLN positivity that may be used to risk-stratify and select patients
      for LM/SL. To confirm these results, the predictive value of MR for SLN
      positivity needs to be validated in other populations of thin-melanoma patients.

PMID- 15864483
TI  - Expression of the transcription factors snail, slug, and twist and their clinical
      significance in human breast cancer.
AB  - BACKGROUND: Slug, Snail, and Twist are transcription factors that regulate the
      expression of tumor suppressors such as E-cadherin. We examined the distribution
      and expression of these three molecules together with the methylation of the
      Twist gene promoter in human breast cancer to elucidate their clinical
      significance. METHODS: Frozen sections from breast cancer primary tumors (tumor,
      n = 114; background, n = 30) were immunostained with Slug, Snail, and Twist
      antibodies. RNA was reverse-transcribed, quantified, and analyzed by quantitative
      polymerase chain reaction (Q-PCR). Results were expressed as copy number of
      transcript per 50 ng of RNA (standardized against beta-actin). RESULTS:
      Immunohistochemistry revealed that all three molecules were stained in mammary
      tissues, with an increase in Twist within tumor tissues; this was supported by Q
      PCR analysis. Q-PCR analysis showed that Slug was elevated with increasing tumor
      grade and prognostic indices. Twist was elevated with increasing nodal
      involvement (tumor-node-metastasis status). Conversely, Snail was reduced in
      expression corresponding with prognostic indices and tumor grade. Increased
      levels of Slug were associated with tumors from patients with metastatic disease
      or disease recurrence, and increased expression of Twist was associated with
      tumors from patients who had died from breast cancer. It is interesting to note
      that Snail expression was significantly reduced in patients with a poor outcome
      and those who had node-positive tumors. In addition, tumors exhibited methylation
      of the Twist promoter. CONCLUSIONS: These data demonstrate that all three
      transcription factors have inappropriate expression in breast cancer and that
      this may play a part in the progression of human breast tumors.

PMID- 15864484
TI  - Isolated limb perfusion with tumor necrosis factor and melphalan prevents
      amputation in patients with multiple sarcomas in arm or leg.
AB  - BACKGROUND: Treatment for extremity soft tissue sarcoma (STS) has shifted in
      recent years from amputation to local wide excision combined with irradiation.
      For multiple sarcomas, this limb-sparing approach is often not possible. To avoid
      amputations, isolated limb perfusion (ILP) with tumor necrosis factor and
      melphalan is an attractive treatment option for patients with multiple extremity
      sarcomas. METHODS: We investigated a prospective database at a tertiary referral
      institute. From July 1991 to July 2003, out of 217 ILPs, 64 ILPs were performed
      for either multifocal primary sarcomas or multiple sarcoma recurrences in 53
      patients. All ILPs were performed under mild hyperthermic conditions by using 1
      to 4 mg of tumor necrosis factor and 10 to 13 mg/L of limb volume for leg and arm
      perfusions, respectively. RESULTS: The overall response was 88%, with 42%
      complete response, 45% partial response, 11% no change, and 2% progressive
      disease. This response rate is significantly better than our experience in 153
      locally advanced single-STS cases (88% vs. 69%). The toxicity of the procedure
      was mild to moderate in almost all cases; no treatment-related amputation had to
      be performed. The time to local recurrence was 29 months and differed
      significantly between multiple primary and multiple recurrent STS. The 5-year
      survival rate was 39%. Limb salvage was achieved in 45 (82%) of 55 treated limbs.
      CONCLUSIONS: In a group of patients who are uniformly candidates for amputation,
      ILP can achieve limb salvage in approximately four out of five patients. Because
      this treatment option provides excellent local control, it should be considered
      before an amputation is planned.

PMID- 15864485
TI  - [Cystic lesion of the dorsal mediastinum].
AB  - We present the case of a 52-year-old male who underwent thoracotomy for resection
      of a suspected bronchogenic cyst in the right posterior mediastinum. The size of
      the tumor had increased over years, according to repeated X-rays, and the cyst
      became symptomatic with obstruction of the right subclavian and jugular veins. To
      our surprise, histopathology revealed a hydatid cyst.

PMID- 15864486
TI  - [Endoscopic examinations of the eustachian tube].
AB  - BACKGROUND AND OBJECTIVE: Endoscopy of the eustachian tube allows direct
      examination of endoluminal alterations in the course of the organ. The aim of
      this study was to describe anatomic and functional findings in healthy awake
      subjects. PATIENTS/METHODS: Ten eustachian tubes in six healthy individuals with
      no history of tube dysfunction were examined under local anesthesia using
      different types of rigid and flexible endoscopes. RESULTS: Nine of ten tubes
      presented with no pathologic finding. The motility of the tube cartilage could be
      visualized in all cases and showed a wide variety. Prior anesthesia of the mucosa
      with the subject in the supine position, if necessary supplemented by a tube
      catheter, rendered the procedure more comfortable. CONCLUSION: The eustachian
      tube shows a wide spectrum of anatomic and functional varieties in normal
      subjects. The method allows comprehensive evaluation of anatomic and functional
      stenoses of the eustachian tube. The transnasal-transpharyngeal approach allows
      only limited evaluation of the middle ear structures.

PMID- 15864487
TI  - [Factorial structure of the BAKO 1-4. On the validation of the "Base competence
      for school years 1-4" test for determining phonological processing].
AB  - BACKGROUND: Phonological awareness in native German speaking school children in
      grades 1 through 4 can be tested using the BAKO 1-4. We raised the question
      whether BAKO 1-4 subtests probe different aspects of phonological processing.
      METHODS: Participants were 62 school children aged 7-12 years. Application of the
      BAKO 1-4 was performed during routine clinical testing. RESULTS: Statistical
      analysis indicated two factors with sufficient loading as latent variables.
      DISCUSSION: Our data indicate that two underlying variables constitute BAKO 1-4
      test performance: the first involves "conscious phonological processing in a
      narrow sense", and the second involves decision making. Two subtests loading on
      factor 2 may be related to the decision making processes. This has to be kept in
      mind when applying the test to indecisive children.

PMID- 15864488
TI  - [Mechatronic in functional endoscopic sinus surgery. First experiences with the
      daVinci Telemanipulatory System].
AB  - BACKGROUND: This study examines the advantages and disadvantages of a commercial
      telemanipulator system (daVinci, Intuitive Surgical, USA) with computer-guided
      instruments in functional endoscopic sinus surgery (FESS). METHODS: We performed
      five different surgical FESS steps on 14 anatomical preparation and compared them
      with conventional FESS. A total of 140 procedures were examined taking into
      account the following parameters: degrees of freedom (DOF), duration , learning
      curve, force feedback, human-machine-interface. RESULTS: Telemanipulatory
      instruments have more DOF available then conventional instrumentation in FESS.
      The average time consumed by configuration of the telemanipulator is around 9+/-2
      min. Missing force feedback is evaluated mainly as a disadvantage of the
      telemanipulator. Scaling was evaluated as helpful. The ergonomic concept seems to
      be better than the conventional solution. DISCUSSION: Computer guided instruments
      showed better results for the available DOF of the instruments. The human-machine
      interface is more adaptable and variable then in conventional instrumentation.
      Motion scaling and indexing are characteristics of the telemanipulator concept
      which are helpful for FESS in our study.

PMID- 15864489
TI  - Analysis of pig-to-human porcine endogenous retrovirus transmission in a triple
      species kidney xenotransplantation model.
AB  - Clinical pig-to-human xenotransplantation might be associated with the risk of
      transmission of xenozoonoses, especially porcine endogenous retroviruses (PERVs).
      We have established a pig-to-humanised-cynomolgus monkey xenotransplantation
      model allowing the analysis of potential PERV-transmission from normal or
      transgenic porcine organs to human vascular tissue. Pig-to-human kidney
      xenotransplantation was performed in cynomolgus monkeys. An interposition graft
      constructed from a human saphena vein replaced the porcine kidney vein. After
      graft rejection and/or death of the recipient (survival 2, 4, 6, 13, 16, 19
      days), the human interposition grafts were removed. Human endothelial cells
      (huECs) were isolated from the interposition grafts and cultivated in vitro.
      Explanted human vascular tissue, isolated huECs, plasma and serum samples of the
      graft recipients were characterised by flow cytometry and immunohistochemistry
      and screened for indications of PERV transmission by quantitative polymerase
      chain reaction (PCR), reverse transcriptase-polymerase chain reaction (RT-PCR)
      and RT assay. PERV-specific immune response of recipients was analysed by Western
      blot. No evidence of PERV infection or PERV-specific immune response was
      detected.

PMID- 15864490
TI  - Successful ablation of atrioventricular accessory pathway after cardiac
      transplantation.
AB  - Liberalization of stringent guidelines regarding donor selection is acceptable in
      the case of critical recipient condition. Few cardiac allografts with preexisting
      accessory atrioventricular pathways have been implanted. We describe the
      successful radiofrequency modification of the atrioventricular node and ablation
      of an accessory pathway after cardiac transplantation. Although the previously
      healthy donor had no history of arrhythmia, the recipient's postoperative course
      was characterized by multiple bouts of reentry tachycardia. The highly successful
      catheter-based ablation techniques available to cure this condition favor the use
      of donor hearts with a preexisting accessory pathway.

PMID- 15864491
TI  - Gold nanoparticle-based electrochemical biosensors.

PMID- 15864497
TI  - Orthogonal signal correction applied to the classification of wine and molasses
      vinegar samples by near-infrared spectroscopy. Feasibility study for the
      detection and quantification of adulterated vinegar samples.
AB  - The most common fraudulent practice in the vinegar industry is the addition of
      alcohol of different origins to the base wine used to produce wine vinegar with
      the objective of reducing manufacturing costs. The mixture is then sold
      commercially as genuine wine vinegar, thus constituting a fraud to consumers and
      an unfair practice with respect to the rest of the vinegar sector. A method based
      on near-infrared spectroscopy has been developed to discriminate between white
      wine vinegar and alcohol or molasses vinegar. Orthogonal signal correction (OSC)
      was applied to a set of 96 vinegar NIR spectra from both original and artificial
      blends made in the laboratory, to remove information unrelated to a specific
      response. The specific response used to correct the spectra was the extent of
      adulteration of the vinegar samples. Both raw and corrected NIR spectra were used
      to develop separate classification models using the potential functions method as
      a class-modeling technique. The previous models were compared to evaluate the
      suitability of near-infrared spectroscopy as a rapid method for discrimination
      between vinegar origin. The transformation of vinegar NIR spectra by means of an
      orthogonal signal-correction method resulted in notable improvement of the
      specificity of the constructed classification models. The same orthogonal
      correction approach was also used to perform a calibration model able to detect
      and quantify the amount of exogenous alcohol added to the commercial product.
      This regression model can be used to quantify the extent of adulteration of new
      vinegar samples.

PMID- 15864499
TI  - Prediction of clozapine metabolism by on-line electrochemistry/liquid
      chromatography/mass spectrometry.
AB  - Combining electrochemical conversion, liquid chromatography and electrospray
      ionization mass spectrometry (EC/LC/ESI-MS) on-line allows the rapid
      identification of possible oxidation products of clozapine (CLZ) in the absence
      and in the presence of glutathione. CLZ is, depending on the applied potential,
      oxidized to various products in an electrochemical flow-through cell using a
      porous glassy carbon working electrode. Several hydroxylated and demethylated
      species are detected on-line using LC/MS. While hydroxy-CLZ is most abundant at a
      potential of 400 mV, demethylation occurs more readily at higher potentials (at
      around 700 mV versus Pd/H(2) reference). In the presence of glutathione (GSH),
      various isomeric glutathione adducts and respective products of further oxidation
      can be identified. The thioadducts are characterized by tandem MS. Mono-GSH and
      bis-GSH derivatives can be seen in the chromatograms. The results correlate well
      with the cyclic voltammetric profile of CLZ. The data are relevant from a
      pharmacological point of view, since similar metabolites (phases I and II) have
      been reported in the literature. The EC/LC/MS and EC/MS methods should be
      valuable tools that can be used to anticipate and understand the metabolization
      patterns of molecules of pharmacological interest and to point out reactive
      intermediates.

PMID- 15864500
TI  - Effect of torpor on the water economy of an arid-zone marsupial, the stripe-faced
      dunnart (Sminthopsis macroura).
AB  - Metabolic rate and evaporative water loss (EWL) were measured for a small, arid
      zone marsupial, the stripe-faced dunnart (Sminthopsis macroura), when
      normothermic and torpid. Metabolic rate increased linearly with decreasing
      ambient temperature (T(a)) for normothermic dunnarts, and calculated metabolic
      water production (MWP) ranged from 0.85+/-0.05 (T(a)=30 degrees C) to 3.13+/-0.22
      mg H2O g(-1) h(-1) (T(a)=11 degrees C). Torpor at T(a)=11 and 16 degrees C
      reduced MWP to 24-36% of normothermic values. EWL increased with decreasing T(a),
      and ranged from 1.81+/-0.37 (T(a)=30 degrees C) to 5.26+/-0.86 mg H2O g(-1) h(-1)
      (T(a)=11 degrees C). Torpor significantly reduced absolute EWL to 23.5-42.3% of
      normothermic values, resulting in absolute water savings of 50-55 mg H2O h(-1).
      The relative water economy (EWL/MWP) of the dunnarts was unfavourable, remaining
      >1 at all T(a) investigated, and did not improve with torpor. Thus torpor in
      stripe-faced dunnarts results in absolute, but not relative, water savings.

PMID- 15864501
TI  - Resting metabolism of mouse papillary muscle.
AB  - The aims of this study were to measure the resting metabolic rate of isolated
      mouse papillary muscles and to determine whether diffusive O2 supply is adequate
      to support the resting metabolism. Resting metabolism of left ventricular
      papillary muscles was measured in vitro (27 degrees C) using the myothermic
      technique. The rate of resting metabolism declined exponentially with time
      towards a steady value, with a time constant of 18+/-2 min (n=13). There was no
      alteration in isometric force output during this time. The magnitude of the
      resting metabolism, which depended inversely on muscle mass, more than doubled
      following a change in substrate from glucose to pyruvate and was increased 2.5
      fold when the osmolarity of the bathing solution was increased by addition of 300
      mM sucrose. Addition of 30 mM 2, 3-butanedione monoxime affected neither the time
      course of the decline in metabolic rate nor the eventual steady value. Analysis
      of the diffusive oxygen supply to the isolated preparation indicated that small
      papillary muscles (mass <1 mg), which have a very high resting metabolic rate
      early in an experiment, are unlikely to be adequately oxygenated.

PMID- 15864502
TI  - Mutation of single murine acetylcholine receptor subunits reveals differential
      contribution of P121 to acetylcholine binding and channel opening.
AB  - The nicotinic acetylcholine receptor (AChR) is a heteropentameric, ligand-gated
      ion channel at the neuromuscular junction, where it is responsible for signal
      transduction between the motorneuron and the muscle. Point mutations in the
      subunits of the receptor change the channel's electrophysiological properties and
      underlie inherited forms of muscle weakness, the congenital myasthenic syndromes.
      One point mutation (P121L) has been identified in the epsilon-subunit of patients
      suffering from the fast-channel congenital myasthenic syndrome, which is evoked
      by reduced AChR openings. We introduced the P121L mutation into all murine AChR
      subunits and performed electrophysiological studies in Xenopus laevis oocytes.
      The P121L mutation in the epsilon-subunit of the adult mouse AChR affected ligand
      binding and channel gating in a manner similar to that described for human AChR.
      At equivalent positions in the alpha- and beta-subunits, the mutation caused only
      minor electrophysiological changes. Mutation of the delta-subunit had similar,
      but less pronounced functional consequences compared to epsilonP121L, reflecting
      the asymmetry of the acetylcholine binding sites and the dominant effect of the
      alpha-epsilon site on channel opening.

PMID- 15864503
TI  - Dopamine is metabolised by different enzymes along the rat nephron.
AB  - The purpose of this study was to determine the basal levels of dopamine (DA) and
      to examine the enzymes involved in DA metabolism in different microdissected
      nephron segments from rat kidneys. Segments were incubated with DA (50 nM) or DA
      plus monoamine oxidase (MAO) or catechol-O-methyl transferase (COMT) inhibitors.
      Basal DA levels were higher in the proximal convoluted tubule (PCT, 10.8+/-3.7
      pg/mm) and in the medullary collecting duct (MCD, 10.9+/-4.0 pg/mm) than in the
      medullary thick ascending limb of Henle's loop (MTAL, 4.9+/-0.9 pg/mm) (P<0.05).
      The percentage of exogenously added DA that was not metabolised was similar in
      both PCT (67+/-13%) and MCD (65+/-5%) and lower in MTAL (35+/-7%), suggesting
      that MTAL is a major site of DA metabolism. Inhibition of MAO (pargyline 1 mM)
      significantly increased the basal content of DA and the percentage of the added
      non-metabolised DA (to 95+/-10%) in PCT but had no effect on MTAL or MCD.
      Conversely, inhibition of COMT (nitecapone or Ro-41-0960, both 1 mM) slightly
      increased the basal levels of DA only in MTAL, whereas the percentage of added DA
      not metabolised rose to 97+/-10% in MTAL and to 91+/-15% in MCD. COMT inhibition
      had no effect in PCT. In conscious rats pargyline (50 mg/kg) increased urinary DA
      from 680+/-34 to 1,128+/-158 ng/d/100 g BW (P<0.01) while nitecapone (40 mg/kg)
      produced a slight non-significant increment. Our results show that DA is present
      all along the rat nephron and that renal DA is metabolised continuously and
      predominantly by MAO in proximal segments, and by COMT in the more distal ones.

PMID- 15864504
TI  - Presence of organic anion transporters 3 (OAT3) and 4 (OAT4) in human
      adrenocortical cells.
AB  - Since the organic anion transporter-1 (OAT1) has been implicated in cortisol
      release from bovine and rat adrenal zona fasciculata cells, we addressed the
      question of whether OATs are present in human adrenal cortical cells. In the
      human adrenal cell line NCI-H295R, 24-h cortisol secretion increased up to 30
      fold on exposure to forskolin. Incubation of forskolin-treated cells for 24 h
      with the OAT substrates probenecid, p-aminohippurate (PAH), glutarate or
      cimetidine inhibited cortisol release partly. RT-PCR did not reveal expression of
      human OAT1 and OAT2, but OAT3 and OAT4 mRNAs were detected in both NCI-H295R
      cells and human adrenal tissue. When human OAT3 (hOAT3) and hOAT4 were expressed
      in Xenopus laevis oocytes, only hOAT3 showed [3H]cortisol uptake in excess of
      that of water-injected control oocytes. Cortisol uptake via OAT3 was saturable
      with an apparent Kt of 2.4 microM. In NCI-H295R cells, [3H]estrone sulphate
      uptake was saturable, cis-inhibited by OAT substrates and trans-stimulated by
      preloading with glutarate or cortisol. Likewise, [3H]PAH uptake was cis-inhibited
      by estrone sulphate and trans-stimulated by preloading the cells with PAH,
      glutarate or cortisol, indicating functional expression of OATs in the plasma
      membrane of NCI-H295R cells.

PMID- 15864505
TI  - Cooperativity and intermediates in the equilibrium reactions of Fe(II,III) with
      ethanethiolate in N-methylformamide solution.
AB  - The reaction of FeCl(2) or FeCl(3) with sodium ethanethiolate (SEt) in N
      methylformamide (NMF) has been reevaluated to rectify a previous Fe(II) oxidation
      artifact. On titrating Fe(II) with EtS(-) concentrations up to 12 mol Eq, new
      features in the UV/vis spectrum (epsilon(344)=(3.1+/-0.2)x10(3) M(-1) cm(-1);
      epsilon(486)=(4.5+/-0.1)x10(2) M(-1) cm(-1)) indicated that the first observable
      step was the formation of a single complex different from the known tetrahedral
      tetrathiolate, [Fe(SEt)(4)](2-) . As the EtS(-) concentration increased past 12.5
      mol Eq the UV/vis spectrum gradually transformed to that of [Fe(SEt)(4)](2-)
      (lambda(max)=314 nm). A Hill-formalism fit to the titration data of the initially
      formed complex indicated cooperative ligation by three ethanethiolate ions, with
      K(coop)=(1.7+/-0.1)x10(3) M(-3) and Hill "n"=2.4+/-0.1 (r=0.997). The 3:1 EtS(-)
      Fe(II) complex is proposed to be [Fe(2)(SEt)(6)](2-). Titration of Fe(III) with
      EtS(-) showed direct cooperative formation of [Fe(SEt)(4)](-)
      [epsilon(340)=(3.4+/-0.5)x10(3) M(-1) cm(-1)] with a Hill-formalism
      K(coop)=(4.3+/-0.1)x10(2) M(-4) and a Hill coefficient "n"=3.7+/-0.2 (r=0.996).
      Further ligation past [Fe(SEt)(4)](-) was observed at EtS(-) concentrations above
      35 mol Eq. The Fe(III) Hill constants are at variance with our previous report.
      However, the UV/vis spectrum of Fe(III) in NMF solution was found to change
      systematically over time, consistent with a slow progressive deprotonation of
      [Fe(nmf)](3+). The observed time-to-time differences in the equilibrium chemistry
      of Fe(III) with ethanethiolate in NMF thus reflect variation in the microscopic
      solution composition of FeCl(3) in alkaline NMF solvent. These results are
      related to the chemistry of nitrogenase FeMo cofactor in alkaline NMF solution.

PMID- 15864506
TI  - [Influence of gender on propofol consumption and recovery times].
AB  - INTRODUCTION: We investigated gender differences of drug consumption and recovery
      times for propofol-remifentanil anaesthesia. METHODS: Adult patients scheduled
      for minor orthopaedic surgery were randomised to receive a propofol-remifentanil
      anaesthesia controlled either by EEG monitoring (Narcotrend or BIS) or solely by
      clinical parameters. Anaesthesia was induced with remifentanil 0.4 microg/kg/min
      and a propofol target-controlled infusion (TCI) at 3.5 microg/ml. After
      intubation remifentanil was reduced to 0.2 microg/kg/min whereas propofol TCI was
      adjusted according to clinical parameters or to the following EEG target values:
      during maintenance to "D(0)" (Narcotrend) or "50" (BIS), 15 min before the end of
      surgery to "C(1)" (Narcotrend) or "60" (BIS). Recovery times were recorded and
      average normalised propofol consumption was calculated from induction and
      maintenance doses. RESULTS: A total of 60 male and 60 female patients completed
      the study. Gender differences were observed for recovery times (with standard
      practice) and for propofol consumption (with BIS monitoring). In the standard
      protocol group, propofol consumption was nearly identical for male and female
      patients whereas recovery times were significantly longer in the male group. In
      both EEG-guided groups propofol consumption was less for male patients while
      recovery times were slightly longer. In the group of female patients higher
      propofol TCI concentrations had to be used to reach the same BIS or Narcotrend
      values. CONCLUSION: With propofol-remifentanil anaesthesia, gender has impact on
      recovery times and propofol consumption. If the same amounts of propofol are
      applied, males awake later, with BIS or Narcotrend monitoring males receive less
      propofol for comparable EEG effects.

PMID- 15864507
TI  - [Shaping the future together].

PMID- 15864508
TI  - [Guidelines of lipid therapy translation into clinical practice].
AB  - Alterations in lipid metabolism play a major role in the pathogenesis of
      atherosclerosis and are an important risk factor for cardiovascular events.
      Lowering of LDL cholesterol by statins reduces morbidity and mortality in
      patients with coronary artery disease (CAD), both in primary and secondary
      prevention. The results of large controlled trials that included more than 50,000
      patients are the basis for target values promoted by current guidelines.
      According to the NCEP-ATP III guidelines LDL cholesterol should be lowered to
      less than 100 mg/dl in high risk patients (CAD or CAD equivalent) and in very
      high risk patients optional to less than 70 mg/dl. Up to now even in high risk
      patients the recommended goals are not sufficiently achieved: Up to 80% of high
      risk patients do not receive a statin and only a minority of those being treated
      with a statin have a LDL cholesterol below 100 mg/dl. Furthermore, after a major
      event (e.g. myocardial infarction) the quality of lipid reduction decreases over
      time. Further efforts are required to improve this situation as a guide-line
      oriented approach may help to prevent up to 100,000 myocardial infarctions and
      deaths alone in high risk patients in Germany.

PMID- 15864510
TI  - [Implantation of a dual head prosthesis. Planning, intervention and care].

PMID- 15864509
TI  - [Prosthetic care of proximal femur fractures].
AB  - The endoprosthetic replacement of the hip joint or its components in fractures of
      the proximal femur is a standard method. Indications for replacement are strongly
      dislocated intracapsular femoral neck fractures in elderly patients, fractures
      with an existing arthritis of the hip joint, and profound osteoporosis. Improved
      perioperative management and more gentle anesthetic techniques have helped to
      reduce perioperative mortality from nearly 50% to 11.5% over the last 40 years.
      As routine treatment options, the bipolar endoprosthesis without replacement of
      the acetabular joint surface and total hip replacement in case of degenerative
      arthritis of the acetabular joint surface are commonly used. The mere replacement
      of the femoral head with a simple femoral head prosthesis should be reserved for
      exceptional cases. For the implantation of a hip joint prosthesis and its
      uncomplicated post-treatment and long-term durability, careful preoperative
      planning is essential together with the selection of a suitable implant, its
      optimal bony fixation, avoidance of intra-operative complications and restoration
      of the anatomical landmarks such as the centre of rotation of the hip joint, the
      offset of the prosthetic shaft as well as leg length. Despite the high standard
      of endoprosthetics in Germany, the results are still improvable in comparison to
      other countries. Measures which preserve the joint as well as the bone will be
      increasingly important in prophylaxis of further complications. In addition, more
      attention should be paid to the prophylaxis of falls and a sufficiently guide
      lined therapy of osteoporosis for the prophylaxis of fractures of the elderly.

PMID- 15864511
TI  - Mating behaviour in a slave-making ant, Rossomyrmex minuchae (Hymenoptera,
      Formicidae).
AB  - The mating behaviour of the ant Rossomyrmex minuchae, a rare, protected slave
      making species in Spain, seems to be significantly affected by its particular
      life history and patchy habitat. The mating behaviour of the entire genus
      Rossomyrmex is virtually unknown. We present here the results of a 3-year study
      of mating behaviour in R. minuchae.Behavioural observations and limited nest
      excavations revealed that R. minuchae does not produce sexuals every year, the
      number of sexuals is low, and the sex ratio tends to be female biased. Females
      typically exhibit two distinct activity periods. The first, the mating period,
      takes place in early afternoon: the ants "call" near the natal nest, mate and
      then return to their nest. The second, the dispersal period takes place in late
      afternoon: the mated females exit their nest and fly in search of a new, non
      parasitized Proformica longiseta host nest. Males are highly active during the
      mating period, but will remain inactive in the dispersal period even if
      experimentally presented with virgin females. It appears that females are
      monogamous, while males are polygamous. When males are late arriving at the
      female calling site, the females will frequently congregate presumably calling in
      chorus. The low reproductive efficiency exhibited by R. minuchae, coupled with
      the postulated low genetic variation in the population, as sisters may mate with
      the same male, could result in a low survival rate and risk of eventual
      extinction. The observed decrease in nest density we observed during the 2004
      season may be indicative of such a process.

PMID- 15864512
TI  - Disease and colony foundation in the dampwood termite Zootermopsis angusticollis:
      the survival advantage of nestmate pairs.
AB  - To determine the impact of inbreeding and outbreeding on disease resistance and
      survival during colony foundation, nestmate (NM) and non-nestmate (NON) primary
      reproductives of the dampwood termite Zootermopsis angusticollis were exposed to
      a single or double dose of conidia of the entomopathogenic fungus Metarhizium
      anisopliae. Male and female primary reproductive pairs originating from the same
      parent colony had higher survivorship than NON pairs in control and conidia
      exposure treatments. The survival advantage of NM primary reproductives increased
      with the intensity of pathogen challenge and was significantly greater in the
      single- and double-dose treatments than in the controls. Although NM pairs had
      significantly lower mortality than NON pairs, the survivorship of colonies
      stabilized as they matured and inbred and outbred colonies did not differ in
      offspring production. These results demonstrate that colony foundation by NON
      male and female reproductives may have a disease-related survival cost during
      this critical phase of their life cycle. There may also be a cost associated with
      lower offspring heterozygosity, but in the first generation this does not appear
      to significantly impact colony growth.

PMID- 15864513
TI  - The earliest modern mongoose (Carnivora, Herpestidae) from Africa (late Miocene
      of Chad).
AB  - We report on the earliest modern mongooses of Africa, from the late Miocene (ca.
      7 Ma) of the hominid locality TM 266, Toros-Menalla, Chad. The material is based
      on fragmentary dentitions of three individuals. The main diagnostic feature of
      the Chadian species is the great development of the shear in the carnassials,
      which distinguishes the Chadian specimens from all extant herpestids except
      Herpestes and Galerella. In comparison with most extinct and extant Herpestes,
      the species from Toros-Menalla differs by a markedly smaller size and, depending
      on the species, relatively more elongated carnassials, more transversely
      elongated M1 and more reduced p4. On the basis of a great morphological
      similarity and the absence of significant differences, we assign our material to
      Galerella sanguinea; the Chadian finding therefore represents the earliest
      appearance of an extant species of Herpestidae. This record ties the first
      appearance of the genus to a minimum age of ca. 7 Ma, which is consistent with
      the estimated divergence date of 11.4 Ma known from the literature for the
      species of Galerella.

PMID- 15864514
TI  - [The value of pharmacogenetic tests in antidepressive medication therapy].
AB  - The pharmacokinetics and effect of antidepressants are influenced by genetic
      factors. Modern methods of genotyping allow fast and inexpensive identification
      of genetic variants and thus can be used in clinical diagnostics to improve the
      tolerance to drug therapy. Numerous studies have investigated the significance of
      genetic variants in drug-metabolizing enzymes, drug and natural substrate
      transporters, neurotransmitter receptors, and molecules involved in signal
      transduction. While the interindividual differences in oral clearance, half-life,
      and bioavailability caused by genetic variants in the cytochrome P450 liver
      enzymes can be overcome by individual adjustment of dosage according to certain
      genotypes, the effects of genetic variants in antidepressive target structures
      are more difficult to translate into clinical recommendations. This article gives
      an overview of the currently available literature and points to situations in
      which the determination of pharmacogenetic variants might change drug therapy or
      therapeutic strategies for the individual patient. Dose adjustments for common
      antidepressant drugs based upon differences in pharmacokinetic parameters caused
      by genetic variability will be given.

PMID- 15864515
TI  - [Neurogenic thoracic outlet syndrome. Long-term results of supraclavicular
      decompression].
AB  - OBJECTIVES: Neurogenic thoracic outlet syndrome (TOS) is one of the most
      controversial entrapment syndromes of the upper extremity. There are two
      different surgical approaches for its primary surgical treatment: supraclavicular
      decompression and transaxillary first rib resection. The aim of this study was to
      evaluate long-term results and surgical risks of the former. METHODS: This
      retrospective long-term study examines a series of 50 supraclavicular
      decompressions in 45 patients. Follow-up was for at least 24 months. All patients
      were reexamined regularly in nonstandardized fashion. Finally, each patient
      underwent a telephone interview with a standardized questionnaire. RESULTS: There
      was a significant deterioration of primary results during follow-up. About 30.0%
      of cases worsened within 24 months after operation. In the long run, about 80.0%
      of cases showed improvement of symptoms (26.0% excellent, 36.0% good, 18.0%
      moderate). The complication rate was 4.0%. CONCLUSION: Due to secondary
      deterioration of treatment during follow-up, only long-term studies are suited
      for the examination of neurogenic TOS. Results after supraclavicular
      decompression are satisfactory, and the complication rate is low.

PMID- 15864516
TI  - [Neurolisteriosis with acute myelitis].
AB  - Listeriosis is a bacterial infection with Listeria monocytogenes mostly affecting
      immunocompromised patients. In every fourth case, the CNS is involved, usually as
      meningoencephalitis. This case report of an immunocompetent woman represents the
      first one of neurolisteriosis initially presenting as cervical myelitis and
      progressing to supratentorial areas of the brain. Diagnosis was based on
      universal polymerase chain reaction from a cortical brain biopsy, followed by
      sequencing of the amplified rDNA gene. Under antibiotic treatment with gentamycin
      and ampicillin, the patient slowly recovered and has been improving ever since.

PMID- 15864517
TI  - [Identity and dissociation in cyberspace. A case of dissociative identity
      disorder associated with internet role playing].
AB  - OBJECTIVE: By mediating dissociative experiences, the Internet can challenge the
      boundaries of people's sense of identity. To illustrate this hypothesis, a case
      of dissociative identity disorder (DID) is presented. CLINICAL PICTURE: A young
      unemployed woman created and frequently played several characters in an online
      game. For more than 2 years she spent up to 12 h a day in the Internet, assuming
      various personalities, which in return intruded upon her neglected real life.
      TREATMENT AND OUTCOME: During the course of an inpatient psychotherapeutic
      treatment, the clinical diagnosis of DID was confirmed by psychometric testing.
      After 12 weeks of psychotherapy, the patient had managed to identify her
      fragmented identities as character traits and integrated them into her core
      personality. She rearranged her real everyday life, found a new job, and reduced
      her online activities. DISCUSSION: Even though the patient's psychopathology
      stems from a disposition in terms of a personality disorder with histrionic and
      narcissistic features, excessive internet role play obviously functioned as a
      trigger to develop DIS. Conclusively, cyberspace's anonymous interactivity may
      offer the possibility to explore one's identity while also putting at risk its
      coherence.

PMID- 15864518
TI  - [Moyamoya disease].
AB  - Moyamoya disease is an idiopathic progressive vasculopathy characterized by
      slowly progressive narrowing involving the distal internal carotid artery and the
      proximal circle of Willis. Collateral vessels develop to compensate for the
      slowly progressive stenosis. These enlarged collaterals appear as a "puff of
      smoke" on angiography, which gives the disease its name. This review discusses
      the clinical manifestation, imaging findings, and angiographic features.

PMID- 15864519
TI  - [Recent studies concerning treatment of acute, ischemic infarcts].
AB  - This article gives an overview over past and present studies concerning the acute
      management of stroke. Stroke trials involving intra-arterial thrombolytic agents,
      either alone or in combination with other therapies, are described.

PMID- 15864520
TI  - [Intestinal inflammatory disease with cholestasis].

PMID- 15864521
TI  - [Basics of acute stroke treatment].
AB  - Acute stroke presents an emergency that requires immediate referral to a
      specialized hospital, preferably with a stroke unit. Disability and mortality are
      reduced by 30% in patients treated in stroke units compared to those treated on
      regular wards, even if a specialized team is present on the ward. Systolic blood
      pressure may remain high at 200-220 mmHg in the acute phase and should not be
      lowered too quickly. Further guidelines for basic care include: optimal O2
      delivery, blood sugar levels below 100-150 mg%, and lowering body temperature
      below 37.5 degrees C using physical means or drugs. Increased intracranial
      pressure should be treated by raising the upper body of the patient,
      administration of glycerol, mannitol, and/or sorbitol, artificial respiration,
      and special monitoring of Tris buffer. Decompressive craniectomy may be
      considered in cases of "malignant" media stroke and expansive cerebellar
      infarction. Fibrinolysis is the most effective stroke treatment and is twice as
      effective in the treatment of stroke than myocardial infarction. Fibrinolysis may
      be initiated within 3 h of a stroke in the anterior circulation. If a penumbra is
      detectable by "PWI-DWI mismatch MRI," specialized hospitals may perform
      fibrinolysis up to 6 h after symptom onset. In cases of stroke in the basilar
      artery, fibrinolysis may be performed even later after symptom onset. Intra
      arterial fibrinolysis is performed in these cases using rt-PA or urokinase.
      Follow-up treatment of stroke patients should not only address post-stroke
      depression and neuropsychological deficits, but also include patient education
      about risk factors such as high blood pressure, diabetes mellitus, and cardiac
      arrhythmias.

PMID- 15864522
TI  - [Diffusion and perfusion MR imaging in stroke].
AB  - Magnetic resonance imaging (MRI) in stroke makes it possible to visualize the
      initial infarct in cases of acute cerebral ischemia. Perfusion MRI serves to
      determine which tissues are additionally at risk of infarction due to persistent
      hypoperfusion. MRI also allows those examiners with limited experience to
      reliably confirm an infarct. The most important differential diagnosis of
      cerebral ischemia, intracerebral hemorrhage, can likewise be recognized with
      certainty using MRI. Although diffusion and perfusion MRI only demonstrate the
      pathophysiology of cerebral ischemia approximately, the method is suited for
      identifying those patients who would profit from reperfusion therapy. Whether MRI
      is also appropriate as an aid to reaching a prognosis on the risk of secondary
      hemorrhage has not yet been resolved.

PMID- 15864523
TI  - Construction of two BAC libraries from cucumber (Cucumis sativus L.) and
      identification of clones linked to yield component quantitative trait loci.
AB  - Two bacterial artificial chromosome (BAC) libraries were constructed from an
      inbred line derived from a cultivar of cucumber (Cucumis sativus L.). Intact
      nuclei were isolated and embedded in agarose plugs, and high-molecular-weight DNA
      was subsequently partially digested with BamHI or EcoRI. Ligation of double size
      selected DNA fragments with the pECBAC1 vector yielded two libraries containing
      23,040 BamHI and 18,432 EcoRI clones. The average BamHI and EcoRI insert sizes
      were estimated to be 107.0 kb and 100.8 kb, respectively, and BAC clones lacking
      inserts were 1.3% and 14.5% in the BamHI and EcoRI libraries, respectively. The
      two libraries together represent approximately 10.8 haploid cucumber genomes.
      Hybridization with a C(0)t-1 DNA probe revealed that approximately 36% of BAC
      clones likely carried repetitive sequence-enriched DNA. The frequencies of BAC
      clones that carry chloroplast or mitochondrial DNA range from 0.20% to 0.47%.
      Four sequence-characterized amplified region (SCAR), four simple sequence repeat,
      and an randomly amplified polymorphic DNA marker linked with yield component
      quantitative trait loci were used either as probes to hybridize high-density
      colony filters prepared from both libraries or as primers to screen an ordered
      array of pooled BAC DNA prepared from the BamHI library. Positive BAC clones were
      identified in predicted numbers, as screening by polymerase chain reaction
      amplification effectively overcame the problems associated with an overabundance
      of positives from hybridization with two SCAR markers. The BAC clones identified
      herein that are linked to the de (determinate habit) and F (gynoecy) locus will
      be useful for positional cloning of these economically important genes. These BAC
      libraries will also facilitate physical mapping of the cucumber genome and
      comparative genome analyses with other plant species.

PMID- 15864524
TI  - DNA hypomethylation in 5-azacytidine-induced early-flowering lines of flax.
AB  - HPLC analysis was used to examine the cytosine methylation of total DNA extracted
      from four early-flowering lines that were induced by treating germinating seeds
      of flax (Linum usitatissimum) with the DNA demethylating agent 5-azacytidine. In
      the normal lines that gave rise to the induced early-flowering lines, flowering
      usually begins approximately 50 days after sowing. The early-flowering lines
      flower 7-13 days earlier than normal. The normal level of cytosine methylation
      was approximately 14% of the cytosines and 2.7% of the nucleosides. In the early
      flowering lines, these levels were 6.2% lower than normal in DNA from the
      terminal leaf clusters of 14-day-old seedlings and 9.7% lower than normal in DNA
      from the cotyledons and immature shoot buds of 4-day-old seedlings. This
      hypomethylation was seen in lines that were five to nine generations beyond the
      treatment generation. The level of hypomethylation was similar in three of the
      four early-flowering lines, but was not as low in the fourth line, which flowers
      early but not quite as early as the other three lines. Unexpectedly, the degree
      of hypomethylation seen in segregant lines, derived by selecting for the early
      flowering phenotype in the F(2) and F(3) generations of out-crosses, was similar
      to that seen in the early-flowering lines. Analysis of the methylation levels in
      segregating generations of out-crosses between early-flowering and normal lines
      demonstrated a decrease in methylation level during the selection of early
      flowering segregants. The results suggest an association between hypomethylation
      and the early-flowering phenotype, and that the hypomethylated regions may not be
      randomly distributed throughout the genome of the early-flowering lines.

PMID- 15864525
TI  - Inheritance of resistance to Xylella fastidiosa within a Vitis rupestris x Vitis
      arizonica hybrid population.
AB  - The inheritance of resistance to Xylella fastidiosa (Xf), the bacterium which
      causes Pierce's disease (PD) in grapevines, was evaluated within a factorial
      mating design consisting of 16 full-sib families with resistance derived from
      Vitis arizonica interspecific hybrids. Measurements of disease progression under
      greenhouse conditions were based on quantitative assessment of Xf populations in
      stem tissues and on three phenotypic scores: leaf scorch, a cane maturation index
      (CMI) and an index that incorporated shoot stunting into the cane maturation
      index (CMSSI). Measurement of bacterial populations yielded the highest broad
      sense heritability for resistance on a genotype mean basis (0.97), indicating
      that this measure of resistance was the least effected by environmental
      variation. Narrow-sense heritability of PD resistance was moderately high and
      measured 0.52, 0.60, 0.63 and 0.37 for Xf populations, CMI scores, CMSSI scores
      and leaf scorch values, respectively. Complex segregation analysis using the
      computer program Statistical Analysis for Genetic Epidemiology (SAGE: ) strongly
      indicated the existence of a major gene for PD resistance, which accounted for
      91% of the total genetic variance. Conversion of the quantitative data into
      qualitative resistance levels and evaluation via a chi-square analysis showed
      that 15 of the 16 families segregated in accordance with a single gene hypothesis
      with a dominant allele controlling PD resistance. These data indicate that the
      trait should be relatively easy to pass on from parents to progeny in a breeding
      program for the development of PD-resistant grape cultivars, particularly when
      selection is based on cane maturation scores or stem Xf populations.

PMID- 15864526
TI  - Diversity and selection in sorghum: simultaneous analyses using simple sequence
      repeats.
AB  - Although molecular markers and DNA sequence data are now available for many crop
      species, our ability to identify genetic variation associated with functional or
      adaptive diversity is still limited. In this study, our aim was to quantify and
      characterize diversity in a panel of cultivated and wild sorghums (Sorghum
      bicolor), establish genetic relationships, and, simultaneously, identify
      selection signals that might be associated with sorghum domestication. We assayed
      98 simple sequence repeat (SSR) loci distributed throughout the genome in a panel
      of 104 accessions comprising 73 landraces (i.e., cultivated lines) and 31 wild
      sorghums. Evaluation of SSR polymorphisms indicated that landraces retained 86%
      of the diversity observed in the wild sorghums. The landraces and wilds were
      moderately differentiated (F st=0.13), but there was little evidence of
      population differentiation among racial groups of cultivated sorghums (F
      st=0.06). Neighbor-joining analysis showed that wild sorghums generally formed a
      distinct group, and about half the landraces tended to cluster by race. Overall,
      bootstrap support was low, indicating a history of gene flow among the various
      cultivated types or recent common ancestry. Statistical methods (Ewens-Watterson
      test for allele excess, lnRH, and F st) for identifying genomic regions with
      patterns of variation consistent with selection gave significant results for 11
      loci (approx. 15% of the SSRs used in the final analysis). Interestingly, seven
      of these loci mapped in or near genomic regions associated with domestication
      related QTLs (i.e., shattering, seed weight, and rhizomatousness). We anticipate
      that such population genetics-based statistical approaches will be useful for re
      evaluating extant SSR data for mining interesting genomic regions from germplasm
      collections.

PMID- 15864527
TI  - Alcohol consumption and type 2 diabetes Meta-analysis of epidemiological studies
      indicates a U-shaped relationship.
AB  - To clarify the relationship between alcohol consumption and type 2 diabetes we
      conducted a meta-analysis of published epidemiological studies. Data from 13
      cohorts were included in the analysis. The results of these studies are
      consistent with regard to moderate alcohol consumption, indicating a protective
      effect in the order of 30% (relative risk [RR]meta = 0.72, 95% CI = 0.67-0.77).
      The reduced risk is seen in men as well as in women, although few studies
      investigated women. No protective effect of high alcohol consumption was seen and
      one cannot rule out that large intakes of alcohol may increase the risk of type 2
      diabetes. Results from published studies suggest a U-shaped relationship between
      alcohol and type 2 diabetes, but this is based on rather few studies with
      heterogeneous design and definitions. It seems important to further investigate
      if, and to what extent, high alcohol consumption increases the risk of type 2
      diabetes. Aspects of moderate alcohol consumption also need further
      investigation; these include type of drink, frequency of drinking, sex and ethnic
      differences.

PMID- 15864528
TI  - Angiotensin-II-induced oxidative stress elicits hypoadiponectinaemia in rats.
AB  - AIMS/HYPOTHESIS: Hypertension, endothelial dysfunction and insulin resistance are
      associated conditions that share oxidative stress and vascular inflammation as
      common features. Adiponectin is an abundant plasma adipokine that plays a
      physiological role in modulating lipid metabolism and exerts a potent anti
      inflammatory activity. We hypothesised that adiponectin levels decrease in
      response to oxidative stress and that this may promote the development of
      hypertension, endothelial dysfunction and insulin resistance. METHODS: Rats were
      infused with angiotensin II (AngII) or its vehicle, either alone or in
      combination with tempo1 (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl), a membrane
      permeable metal-independent superoxide dismutase mimetic, or tetrahydrobiopterin
      (BH4), one of the most potent naturally occurring reducing agents and an
      essential cofactor for nitric oxide synthase activity. Heart rate, systolic blood
      pressure, body weight and serum levels of adiponectin were measured on day 7 of
      treatment, and then the animals were killed. Vessel tone and superoxide
      production were measured ex vivo in thoracic vascular rings. The expression of
      adiponectin mRNA in adipose tissue was assessed by Northern blotting, and in 3T3
      L1 adipocytes exposed to H2O2 by real-time PCR. The expression of NAD(P)H oxidase
      subunit mRNAs in the rats was assessed by RT-PCR and real-time PCR. RESULTS:
      Hypertension and endothelial dysfunction were induced in rats by infusion of
      AngII and reversed by administration of tempol. Plasma concentrations of
      adiponectin and adipose tissue levels of adiponectin mRNA were decreased in AngII
      infused rats, and this effect was prevented by cotreatment with tempol or BH4.
      The production of superoxide anions (O2-) was significantly increased in the
      aortae of AngII-treated rats, and this increase was prevented by the
      administration of tempol or BH4. Levels of mRNAs that encode NAD(P)H oxidase
      components, including p22phox, gp91phox, p47phox and Rac1, were similarly
      increased in adipose tissue, aortae and hearts of AngII-infused rats. Cotreatment
      of rats with tempol or BH4 reversed AngII-induced increases in NAD(P)H oxidase
      subunit mRNAs. Fully differentiated 3T3-L1 adipocytes, also exhibited diminished
      adiponectin mRNA levels when exposed to low concentrations of H2O2.
      CONCLUSIONS/INTERPRETATION: Our results demonstrate that AngII-induced oxidative
      stress and endothelial dysfunction are accompanied by a decrease in adiponectin
      gene expression. Since antioxidants were observed to prevent the actions of
      AngII, and H2O2 on its own suppressed adiponectin expression, we conclude that
      adiponectin gene expression is negatively modulated by oxidative stress. Plasma
      adiponectin levels may provide a useful indicator of oxidative stress in vivo,
      and suppressed levels may contribute to the proinflammatory and metabolic
      derangements associated with type 2 diabetes, coronary artery disease and the
      metabolic syndrome.

PMID- 15864530
TI  - Leptin resistance exacerbates diet-induced obesity and is associated with
      diminished maximal leptin signalling capacity in rats.
AB  - AIMS/HYPOTHESIS: Leptin resistance is generally considered a consequence of
      obesity. We postulated that leptin resistance is associated with diminished
      hypothalamic leptin signalling capacity and that leptin resistance is causal to
      obesity. We assessed maximal leptin-mediated binding of the transcription factor
      signal transducer and activator of transcription 3 (STAT3), and the response to
      high-fat feeding in lean leptin-resistant rats. MATERIALS AND METHODS:
      Recombinant adeno-associated virus encoding rat leptin cDNA (rAAV-leptin) or
      control vector were administered by intracerebroventricular injection to lean
      F344 x BN rats for up to 150 days, and food consumption, body weight, serum
      leptin and glucose tolerance were measured. Leptin-mediated hypothalamic
      transcription factor binding was assessed at day 150 following an
      intracerebroventricular injection of 2 mug leptin. Rats pretreated with either
      control or rAAV-leptin vector for 94 days were given a high-fat diet, and energy
      intake, body weight gain and adiposity were examined. RESULTS: The rAAV-leptin
      treated rats initially responded to leptin gene delivery then became leptin
      resistant. They displayed persistent submaximal hypothalamic leptin signalling
      and enhanced insulin sensitivity, yet maximal hypothalamic signalling capacity
      was decreased by more than 50%. On a high-fat diet, the leptin-resistant rats
      consumed more energy, gained more weight and accumulated greater visceral fat
      mass than controls. CONCLUSIONS/INTERPRETATION: The maximal hypothalamic leptin
      signalling capacity was diminished in leptin-resistant rats receiving central
      rAAV-leptin gene therapy. Moreover, this leptin-invoked leptin resistance
      perturbs the regulation of energy homeostasis in response to high fat exposure,
      producing augmented energy consumption. This, coupled with potential
      hypersensitivity to insulin, creates a milieu favouring fat deposition. Our data
      suggest that leptin resistance is both a consequence and cause of obesity.

PMID- 15864531
TI  - Regulation of human resistin gene expression in cell systems: an important role
      of stimulatory protein 1 interaction with a common promoter polymorphic site.
AB  - AIMS/HYPOTHESIS: Resistin is an adipokine that might link obesity and insulin
      resistance. A common polymorphism of the human resistin gene, -420C >G, is a
      major determinant of plasma resistin concentrations as well as resistin mRNA
      expression in human adipose tissue. In this study, we investigated the regulatory
      mechanism by which this polymorphism affects resistin expression. METHODS:
      Electrophoretic mobility shift assay was performed to identify the transcription
      factors binding to the -420G region. Transient transfection and reporter assay
      were used to measure promoter activities of the resistin gene. The binding
      ability of stimulatory protein 1 (Sp1) in response to adipocyte differentiation
      or high glucose concentrations was also measured. RESULTS: Sp1 and stimulatory
      protein 3 (Sp3) specifically bound to the region around -420G of the human
      resistin gene. Overexpression of Sp1 increased the promoter activity regardless
      of -420 genotypes, while the promoter activity of the -420G construct was two
      fold higher than that of the -420C construct. In contrast, overexpression of Sp3
      scarcely increased the promoter activity. The binding ability of Sp1 to the -420G
      region was increased in response to adipocyte differentiation. Mithramycin A, an
      inhibitor of DNA binding of Sp1, reduced the effect of high glucose on
      transcription induction of the resistin gene in adipocytes.
      CONCLUSIONS/INTERPRETATION: These results suggest that Sp1 is an important factor
      regulating transcription of human resistin gene. A common polymorphism of the
      human resistin promoter, -420C >G, is critical for the binding of Sp1 and
      modulates the transcriptional activity of the resistin gene by changing the
      binding ability of Sp1. In addition, Sp1 may be involved in the increase of
      resistin expression by hyperglycaemia.

PMID- 15864532
TI  - Birthweight and risk of type 1 diabetes in children and young adults: a
      population-based register study.
AB  - AIMS/HYPOTHESIS: We investigated the association between type 1 diabetes and
      birthweight by age at disease onset. METHODS: This population-based case-referent
      study used data from two nationwide case registers that are linked to the Swedish
      Medical Birth Registry and cover incident cases of type 1 diabetes in the 0- to
      14-year (since 1 July 1977) and 15- to 34-year age groups (since 1 January 1983).
      Of the cases linked to the Medical Birth Registry, a total of 9,283 cases with
      onset before 15 years of age was recorded before 1 January 2003, and 1,610 cases
      were recorded with onset before 30 years of age and born after 1973 (together 95%
      of eligible cases). Multiple births and babies of diabetic mothers were excluded.
      Sex-specific birthweight by gestational week is expressed as multiples of the
      standard deviation (SDS) and adjusted for year of birth, maternal age and parity.
      RESULTS: Cases with onset before 10 years of age (n = 5,792) showed a significant
      linear trend in odds ratio (OR) by SDS of adjusted birthweight (OR by SDS: 0.062;
      95% CI: 0.037-0.086; p < 0.0001), while cases with onset at the age of 10-29
      years showed no significant trend (OR by SDS: 0.004; 95% CI: -0.007 to 0.0014; p
      = 0.22). CONCLUSIONS/INTERPRETATION: The association between type 1 diabetes risk
      and birthweight seems to be limited to cases with disease onset in younger years.

PMID- 15864529
TI  - An immune origin of type 2 diabetes?
AB  - Subclinical, low-grade systemic inflammation has been observed in patients with
      type 2 diabetes and in those at increased risk of the disease. This may be more
      than an epiphenomenon. Alleles of genes encoding immune/inflammatory mediators
      are associated with the disease, and the two major environmental factors the
      contribute to the risk of type 2 diabetes-diet and physical activity-have a
      direct impact on levels of systemic immune mediators. In animal models, targeting
      of immune genes enhanced or suppressed the development of obesity or diabetes.
      Obesity is associated with the infiltration and proinflammatory activity of
      macrophages in adipose tissue, and immune mediators may be important regulators
      of insulin resistance, mitochondrial function, ectopic lipid storage and beta
      cell dysfunction or death. Intervention studies targeting these pathways would
      help to determine the contribution of an activated innate immune system to the
      development of type 2 diabetes.

PMID- 15864533
TI  - Cardiac dysfunction induced by high-fat diet is associated with altered
      myocardial insulin signalling in rats.
AB  - AIMS/HYPOTHESIS: Diabetic cardiomyopathy (DCM) is common in type 2 diabetes. In
      DCM, insulin resistance may alter cardiac substrate supply and utilisation
      leading to changes in myocardial metabolism and cardiac function. In rats,
      exposure to excessive alimentary fat, inducing a type 2 diabetic phenotype, may
      result in myocardial insulin resistance and cardiac functional changes resembling
      DCM. MATERIALS AND METHODS: Rats received high-fat (HFD) or low-fat (LFD) diets
      for 7 weeks. Prior to killing, insulin or saline was injected i.p. Contractile
      function and insulin signalling were assessed in papillary muscles and
      ventricular lysates, respectively. RESULTS: Fasting and post-load blood glucose
      levels were increased in HFD- vs LFD-rats (all p < 0.02). Mean heart weight, but
      not body weight, was increased in HFD-rats (p < 0.01). HFD-hearts showed
      structural changes and triglyceride accumulation. HFD-muscles developed higher
      baseline and maximum forces, but showed impaired recovery from higher workloads.
      Insulin-associated modulation of Ca2+-induced force augmentation was abolished in
      HFD-muscles. HFD reduced insulin-stimulated IRS1-associated phosphatidylinositol
      3'-kinase activity and phosphorylation of protein kinase B, glycogen synthase
      kinase-3beta, endothelial nitric oxide synthase, and forkhead transcription
      factors by 40-60% (all p < 0.05). Insulin-mediated phosphorylation of
      phospholamban, a critical regulator of myocardial contractility, was decreased in
      HFD-hearts (p < 0.05). CONCLUSIONS/INTERPRETATION: HFD induced a hypertrophy-like
      cardiac phenotype, characterised by a higher basal contractile force, an impaired
      recovery from increased workloads and decreased insulin-mediated protection
      against Ca2+ overload. Cardiac dysfunction was associated with myocardial insulin
      resistance and phospholamban hypophosphorylation. Our data suggest that
      myocardial insulin resistance, resulting from exposure to excessive alimentary
      fat, may contribute to the pathogenesis of diabetes-related heart disease.

PMID- 15864534
TI  - Alterations of lipids and apolipoprotein CIII in very low density lipoprotein
      subspecies in type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Very low density lipoprotein (VLDL) particles are heterogeneous,
      comprising two main subspecies, VLDL 1 (Sf 60-400) and VLDL 2 (Sf 20-60). The aim
      of the study was to examine the distribution and composition of VLDL subspecies
      in type 2 diabetes. SUBJECTS, MATERIALS AND METHODS: We studied the composition
      and concentration of triglyceride-rich lipoproteins (TRLs) in 217 type 2 diabetic
      patients and 93 control subjects between 50 and 75 years of age. Lipoprotein
      subspecies were separated by density-gradient ultracentrifugation. Apolipoprotein
      (apo) CIII and apo E in plasma and apo CIII in TRL subspecies were measured by
      nephelometry and apo CII in serum by a commercial kit using a single radial
      immunodiffusion method. RESULTS: The concentrations of VLDL 1, VLDL 2 and
      intermediate density lipoprotein were significantly increased in type 2 diabetes
      subjects, the change being most marked for VLDL 1. There was a strong linear
      correlation between VLDL 1 triglycerides and plasma triglycerides in both groups
      (r = 0.879, p < 0.001 and r = 0.899, p < 0.001). Diabetic subjects had markedly
      higher plasma ratios of apo CII:apo CIII and apo CIII:apo E. Despite elevated
      plasma apo CIII, type 2 diabetic subjects had a relative deficiency of apo CIII
      in all TRL subspecies, suggesting profound disturbances of apo CIII metabolism.
      CONCLUSIONS/INTERPRETATION: The elevation of VLDL 1 triglycerides is the major
      determinant of plasma triglyceride concentration in normal subjects and in type 2
      diabetic individuals. Both apo CIII and apo E metabolism are disturbed in type 2
      diabetes.

PMID- 15864535
TI  - Hyperglycaemia increases dipeptidyl peptidase IV activity in diabetes mellitus.
AB  - AIMS/HYPOTHESES: Chronic hyperglycaemia increases dipeptidyl peptidase IV (DPP
      IV) activity in endothelial cells in vitro. The present study was designed to
      assess the effect of high glucose on circulating DPP-IV activity in patients with
      type 1 and type 2 diabetes. METHODS: Plasma DPP-IV activity was measured in 29
      patients with type 1 diabetes and 29 age-, sex- and BMI-matched control subjects.
      We also assessed DPP-IV activity in 31 type 2 diabetic patients with HbA1c > 8.5%
      and in plasma from matched groups of 31 newly diagnosed diabetic subjects with
      HbA1c < 7.5%, 31 subjects with IGT and 62 subjects with NGT. In a further sample
      of 66 type 2 diabetic patients, a longitudinal study was also performed to
      evaluate variations in DPP-IV activity and HbA1c over 3 months. RESULTS: DPP-IV
      activity in type 1 diabetic patients was not significantly different from that in
      control subjects; however, a significant correlation between DPP-IV and HbA1c was
      observed in diabetic subjects (r = 0.47; p < 0.01). Type 2 diabetic patients with
      HbA1c > 8.5% showed significantly (p < 0.05) higher DPP-IV activity (mean+/-SD
      27.7+/-7.1 U/l) than newly diagnosed diabetic patients and subjects with IGT
      (22.1+/-6.0 and 18.8+/-8.8 U/l, respectively). Variations in DPP-IV activity over
      3 months in type 2 diabetic patients showed a significant positive correlation
      with variations in HbA1c (r = 0.26; p < 0.05). CONCLUSIONS/INTERPRETATION:
      Chronic hyperglycaemia induces a significant increase in DPP-IV activity in type
      1 and type 2 diabetes. This phenomenon could contribute to the reduction in
      circulating active glucagon-like peptide-1 and to the consequent postprandial
      hyperglycaemia in type 2 diabetic patients with poor metabolic control.

PMID- 15864536
TI  - Adult BMI and fat distribution but not height amplify the effect of low
      birthweight on insulin resistance and increased blood pressure in 20-year-old
      South Africans.
AB  - AIMS/HYPOTHESIS: We examined whether associations between low birthweight and
      adult chronic cardio-metabolic disease were dependent upon birthweight alone, or
      on interactions with BMI, fat accumulation either generally or abdominally, or
      attained height in young South African adults. METHODS: Blood pressure (BP),
      lipids, glucose tolerance, insulin sensitivity and secretion (homeostasis model)
      were measured in 20-year-olds (n = 132) born at full term and with birthweights
      on or below the tenth centile (underweight for gestational age [UFA]) or between
      the 25th and 75th centiles for gestational age (appropriate weight for
      gestational age, [AFA]). Sex-specific median measurements of BMI, waist
      circumference, percentage body fat and height defined current anthropometric
      status, providing four groups for each measure: UFA-low or UFA-high and AFA-low
      or AFA-high. RESULTS: The UFA-high BMI group was more insulin-resistant than both
      low BMI groups (p < 0.04), but not the AFA-high BMI group. In contrast, plasma
      triglycerides and systolic BP were higher in the UFA-high than in all other
      groups (all p < 0.04). When characterised by body fatness, both high percentage
      (%) body fat groups had higher fasting [insulin] than low percentage (%) body fat
      groups (p < 0.03), and higher [total cholesterol] and [LDL cholesterol] than the
      UFA-low percentage (%) body fat group (p < 0.05). The UFA-high group had higher
      systolic and diastolic BP than all other groups (all at least p < 0.03). A
      similar pattern was observed when groups were characterised by waist
      circumference; however, current height status had no effect.
      CONCLUSIONS/INTERPRETATION: These data indicate that the "fetal origins"
      expression of the chronic disease phenotype is not dependent on birthweight
      alone, but on its interaction with subsequent fat accumulation, though not on
      attained height, in this cohort of young adults.

PMID- 15864537
TI  - Are ethnic differences in insulin sensitivity explained by variation in
      carbohydrate intake?
AB  - AIMS/HYPOTHESIS: Minority populations are disproportionately affected by
      diabetes. This health disparity may be due to less healthy diets and/or heritable
      factors in minority populations. These factors must be assessed concurrently to
      better appreciate their contribution to insulin sensitivity. METHODS: We analysed
      overweight, healthy adults using the National Health and Nutrition Examination
      Survey 1999-2000. Means for dietary intake variables and insulin sensitivity were
      calculated by ethnicity. Linear regressions were performed to evaluate the
      association between ethnicity, dietary variables, dietary glycaemic index and
      insulin sensitivity. Fasting insulin was used to characterise insulin
      sensitivity. RESULTS: Non-Hispanic whites have higher energy and fat intake,
      while Hispanics have higher carbohydrate intake and African-Americans have lower
      fibre intake. In unadjusted analyses both Hispanics and African-Americans have
      lower insulin sensitivity, but only Hispanics are more likely to have lower
      insulin sensitivity after controlling for dietary variables and BMI.
      CONCLUSIONS/INTERPRETATION: Ethnic differences in insulin sensitivity remain
      after controlling for dietary differences and other factors, suggesting that
      inherent metabolic differences exist. Further studies are needed to define
      inherent metabolic factors, as well as other non-dietary factors that affect
      insulin sensitivity.

PMID- 15864538
TI  - The influence of type 2 diabetes on fibrin structure and function.
AB  - AIMS/HYPOTHESIS: The precise mechanisms underlying the increased risk of
      cardiovascular disease (CVD) in type 2 diabetes are unclear. Fibrin clot
      structure has been related to CVD risk in the general population. We therefore
      assessed this in type 2 diabetic patients as a potential mechanism whereby
      diabetes influences CVD risk. METHODS: Fibrin clots were formed from fibrinogen
      purified from 150 subjects with type 2 diabetes and varying degrees of glycaemic
      control (assessed by HbA1c), and from 50 matched control subjects. Clot structure
      was assessed by turbidity, permeation and confocal microscopy. The specific
      effect of glucose itself was assessed by analysing the structure of clots formed
      from purified fibrinogen in the presence of increasing concentrations of the
      sugar. RESULTS: Clots formed by fibrinogen purified from type 2 diabetic subjects
      had a denser, less porous structure than those from control subjects. The
      structural changes found were related to the individual's glycaemic control;
      HbA1c correlated negatively with permeation coefficient (Ks) values (indicates
      clot pore size) (r = -0.57, p < 0.0001) and positively with maximum absorbance
      (indicator of fibre size) (r = 0.33, p < 0.0001), branch point number (r = 0.78,
      p < 0.0001) and fibre density (r = 0.63, p < 0.0001). The ambient glucose level
      influenced clot structure; hypo- (< 5 mmol) and hyperglycaemia (> or = 10 mmol/l)
      were both associated with a reduction in Ks values and maximum absorbance, and
      with increased fibre density and branch point number within clots.
      CONCLUSIONS/INTERPRETATION: The structural differences found to occur in type 2
      diabetes and in association with hypo- and hyperglycaemia may confer increased
      resistance to fibrinolysis, and in consequence contribute to the increase in CVD
      risk in diabetic patients.

PMID- 15864539
TI  - Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin
      or rosiglitazone is associated with increased mRNA expression of GLUT4 and
      peroxisomal proliferator activator receptor gamma co-activator 1.
AB  - AIMS/HYPOTHESIS: The aim of this study was to determine the effect of several
      antidiabetic agents on insulin-stimulated glycogen synthesis, as well as on mRNA
      expression. METHODS: Cultured primary human skeletal myotubes obtained from six
      healthy subjects were treated for 4 or 8 days without or with glucose (25
      mmol/l), insulin (400 pmol/l), rosiglitazone (10 micromol/l), metformin (20
      micromol/l) or the AMP-activated kinase activator 5-aminoimidazole-4-carboxamide
      ribonucleoside (AICAR) (200 micromol/l). After this, insulin-stimulated glycogen
      synthesis was determined. mRNA levels of the glucose transporters GLUT1 and
      GLUT4, the peroxisomal proliferator activator receptor gamma (PPAR gamma) co
      activator 1 (PGC1) and the myocyte-specific enhancer factors (MEF2), MEF2A, MEF2C
      and MEF2D were determined using real-time PCR analysis after 8 days exposure to
      the various antidiabetic agents. RESULTS: Insulin-stimulated glycogen synthesis
      was significantly increased in cultured human myotubes treated with insulin,
      rosiglitazone or metformin for 8 days, compared with non-treated cells.
      Furthermore, an 8-day exposure of myotubes to 25 mmol/l glucose impaired insulin
      stimulated glycogen synthesis. In contrast, treatment with AICAR was without
      effect on insulin-mediated glycogen synthesis. Exposure to insulin, rosiglitazone
      or metformin increased mRNA expression of PGC1 and GLUT4, while AICAR or 25
      mmol/l glucose treatment increased GLUT1 mRNA expression. Metformin also
      increased mRNA expression of the MEF2 isoforms. CONCLUSIONS/INTERPRETATION:
      Enhanced insulin-stimulated glycogen synthesis in human skeletal muscle cell
      culture coincides with increased GLUT4 and PGC1 mRNA expression following
      treatment with various antidiabetic agents. These data show that chronic
      treatment of human myotubes with insulin, metformin or rosiglitazone has a direct
      positive effect on insulin action and mRNA expression.

PMID- 15864540
TI  - [Snowboarding. History--injuries--risks--new materials--tournament on-site
      services--prevention].
AB  - Since the 1998 Olympic Winter Games in Nagano, snowboarding has been established
      as a popular winter sport for youth and adults. The most frequently affected body
      region reported in many studies on snowboarding injuries are the wrists
      accounting for more than 50% of severe injuries, especially in beginners. Wrist
      braces are effective in protecting snowboarding beginners against wrist injuries.
      Male snowboarders up to the age of 16 and female snowboarders over the age of 25
      have a higher risk of injury. Snowboarders should not use ski boots and should be
      careful with rented equipment. Systems providing body and limb protection and
      also snowboard-specific helmets can reduce the injury risk for alpine racers,
      freestylers, and also freeriders. Snowboard training is important to prevent
      injuries especially for beginners, and icy slopes should be avoided.

PMID- 15864541
TI  - [Trendy sport: golf].
AB  - Golf is currently the most frequently played sport in the world and it will
      continue to grow in importance. Nevertheless, there is a striking deficit in our
      knowledge of the physical and psychological profile of golfers. In the foreground
      are not the acute but the chronic sport specific injuries, predominantly of the
      lumbar spine, the upper extremities (golfer's elbow and golfer's shoulder), and
      less commonly of the lower limbs (minor injuries to the ligaments). In addition
      to therapy, prophylaxis should also be used in order to better recognise and
      influence the sport specific burdens.

PMID- 15864542
TI  - [Kitesurfing injuries. A trendy youth sport ].
AB  - The aim of this review article is to give an overview of current knowledge on
      kitesurfing injuries. As part of a prospective study, the overall self-reported
      injury rate was 7.0 per 1000 h of practice. One fatal accident and 11 severe
      injuries occurred. The most commonly injured sites were foot and ankle, head,
      chest, and knee. Contusions, abrasions, and lacerations were amongst the most
      frequent injuries. None of the athletes suffering a head injury used a helmet;
      the board had been flung against the head by the elastic board leech in all
      cases. The most common injury situation was the jump. Fifty-six percent of the
      injuries were attributed to the inability to detach the kite from the harness.
      There was a tendency that athletes using a quick release system, which enables
      the surfers to detach the kite in emergency situations, sustained fewer injuries
      than athletes without such a release system. In conclusion, kitesurfing is a
      sport with a comparably high injury rate. Preventive measures can reduce the
      injury rate considerably.

PMID- 15864543
TI  - [Women's soccer. Injuries, risks, and prevention].
AB  - Women's soccer participation is becoming a trend in sport. With increasing number
      of licensed female soccer players, there is also an increase in sport specific
      injuries. This fact has socioeconomic importance. The larger pelvic bone leading
      to an increased internal rotation of the femur, the narrower intercondylar notch
      as well as the unfavorable strength ratio of the hamstrings vs. the quadriceps
      muscle lead to an increased risk for injuries of the anterior cruciate ligament
      in female soccer.Several studies showed that intervention programs based on
      neuromuscular or proprioceptive training or intensive strengthening of the
      hamstrings can reduce the incidence of injuries. Moreover, the importance of
      sufficient rehabilitation after injuries has to be emphasized, as the
      reoccurrence of injury is high.

PMID- 15864544
TI  - [Frequency and severity of callus defects. Dorsomedial vs ventrolateral approach
      for corticotomy in performing callus distraction of the tibia].
AB  - BACKGROUND: The purpose of this study was to compare a dorsomedial to the
      ventrolateral approach for corticotomy in performing callus distraction of the
      proximal metaphyseal tibia. PATIENTS AND METHODS: A total of 31 callus
      distractions were performed in 28 humans. The ventrolateral approach was used for
      18 and the dorsomedial approach for 13 corticotomies. A scale of four severity
      grades was used to classify callus defect zones based on their extent as
      evidenced on serial X-rays. Biopsies were taken from higher-grade defects (grades
      3-4). RESULTS: A total of 13 radiological evaluations revealed 12 defects using
      the ventrolateral approach. Seven defects (grades 1-2) healed spontaneously,
      whereas six defects (grades 3-4) required operative intervention as histological
      tissue examination showed no osteogenic potential. CONCLUSION: To prevent callus
      defects of the proximal tibia in the future and to ensure maximal osteogenic
      potential in the distraction zone, a minimally invasive dorsomedial approach
      appears to achieve favorable results.

PMID- 15864545
TI  - Euthanasia, therapeutic obstinacy or something else? An Italian case.

PMID- 15864546
TI  - A prospective study of outcome predictors after severe brain injury in children.
AB  - OBJECTIVE: To directly compare the predictive powers of somatosensory evoked
      potentials (SEPs) to those of motor and pupillary responses. DESIGN AND SETTING:
      Prospective clinical study in a paediatric intensive care unit. PATIENTS AND
      PARTICIPANTS: 102 severely brain-injured children less than 15 years of age.
      MEASUREMENTS AND RESULTS: SEPs and motor and pupillary responses were serially
      recorded during the first 9 days after admission. Initial, last and those tests
      performed on or after day 2 were analysed. Outcome was assessed 5 years after
      injury. SEPs had equal or superior predictive statistics and ROC curves compared
      to the other tests with few exceptions. Pupillary responses had higher
      sensitivity for favourable outcome prediction while for unfavourable outcome
      prediction the last motor responses had higher sensitivity, and the last
      pupillary responses had slightly higher specificity. Combining SEPs and motor
      responses provided the best combination for predicting unfavourable outcome.
      CONCLUSIONS: SEPs are the best overall predictor of outcome while motor and
      pupillary responses have advantages in some specific areas. The routine use of
      SEPs should be considered in the prediction of outcome of severely brain-injured
      patients.

PMID- 15864547
TI  - Neovascularisation in chronic tendon injuries detected with colour Doppler
      ultrasound in horse and man: implications for research and treatment.
AB  - Recent research on chronic painful Achilles tendons in humans using
      ultrasonography and immunohistochemistry, has demonstrated an association between
      neurovascular ingrowth and tendon pain. In horses, chronic debilitating tendon
      conditions are well-known to be very difficult to treat, and the background to
      impaired function and pain is not scientifically clarified. In a collaborative
      research project between the Sports Medicine Unit in Umea and Stromsholm Equine
      Hospital, grey-scale ultrasonography (US) and colour Doppler (CD) examination
      were performed in ten horses with chronic tendon injuries (>3 months) and a
      control group of six healthy and asymptomatic horses. In all symptomatic tendons,
      but not in any of the tendons in the control group, neovessels were seen in the
      area with structural tendon changes. The neovessels found in the horse tendons
      looked similar to what has recently been presented in human Achilles tendons.
      These findings motivate evaluation of the same treatment, a sclerosing injection
      that was demonstrated recently to give promising results in the treatment of
      chronic Achilles tendon injuries (tendinosis) in humans.

PMID- 15864548
TI  - Open Bankart repair with suture anchors for traumatic recurrent anterior shoulder
      instability: comparison of results between small and large Bankart lesions.
AB  - This retrospective study was to demonstrate the clinical outcome of open Bankart
      repair with suture anchors for recurrent anterior shoulder instability, and to
      compare surgical results of small (<3 clock units) and large (>3 clock units)
      Bankart lesions. With an average follow-up of 55.6 months (2-8 years), there were
      82 patients (60 right, 22 left shoulders) with the mean age of 27 years accepting
      open Bankart repair with suture anchors and capsular shift procedure by the same
      team. According to surgical findings, these patients were grouped into small (<3
      clock units) and large (>3 clock units) Bankart lesions. Subjective outcomes were
      recorded according to the Bankart scoring system of Rowe. Rowe scores averaged
      85.9+/-12.9 (range 25-100). The patients, 92-7 %, had objectively excellent or
      good results. Twenty nine patients (35.4%) had small Bankart lesions and 53
      patients had large Bankart lesions. The Rowe scores in small Bankart lesions were
      better than that in large Bankart lesions (93.5+/-6.8 vs. 81.8+/-13.6, Wilcoxon
      rank sum test, P<0.001). Mean scores of stability (Wilcoxon rank sum test,
      P=0.043), motion (Wilcoxon rank sum test, P=0.037), and function (Wilcoxon rank
      sum test, P<0.001) in small lesions also had superior outcomes than in large
      lesions. Four patients (4.9%) got fair results and two (2.4%) patients got poor
      results at the end of follow-up. The average loss of external rotation is 10
      degrees . Open Bankart repair with the aid of suture anchors still got
      satisfactory results in the treatment of traumatic recurrent anterior instability
      of the shoulder. The size of the Bankart lesion was a factor affecting surgical
      outcome. Small Bankart lesions usually got better results than large Bankart
      lesions.

PMID- 15864549
TI  - ACL graft can replicate the normal ligament's tension curve.
AB  - The anatomical femoral insertion of the normal anterior cruciate ligament (ACL)
      lies on the deep portion of the lateral wall of the intercondylar fossa.
      Following the deep bone-cartilage border, it stretches from 11 o'clock high in
      the notch all the way down to its lowest border at 8 o'clock. The tension curve
      of the normal ACL during passive flexion-extension shows a characteristic pattern
      with two tension peaks, one in full extension and the other in deep flexion. Low
      tension in mid-flexion is measured between those two peaks. Standard ACL
      reconstructions use a femoral insertion at 11 o'clock, which results in non
      physiological tension curves with one peak in full extension only. The hypothesis
      was that it is possible to reproduce the typical tension curve of the normal ACL
      by placing the femoral tunnel into the low part of the normal ACL footprint. In a
      controlled laboratory study, three different femoral tunnel positions at 9, 10
      and 11 o'clock were tested in four cadaver knees while using the identical
      standard tibial tunnel each time. The tension curve was measured during passive
      flexion-extension with a custom-made tension measurement device, using an
      artificial Dacron graft. The tension curve of grafts in the 9 o'clock tunnels
      showed the characteristic pattern of the normal ACL's tension curve with tension
      peaks in extension as well as in deep flexion. The tunnels in the 10 and 11
      o'clock positions failed to reproduce the normal ACL's tension curve with high
      tension values in extension only. CLINICAL RELEVANCE: If an ACL graft is placed
      low within the normal femoral footprint, the physiological tension curve of the
      normal ACL can be reproduced.

PMID- 15864550
TI  - Lactobacillus plantarum ccl gene is non-essential, arginine-repressed and codes
      for a conserved protein in Firmicutes.
AB  - Among proteins specifically found in most gram-positive bacteria of the phylum
      Firmicutes, conserved proteins of the family pfam06177-DUF988-COG4708 are of
      unknown function. The citrulline cluster-linked (ccl) gene of Lactobacillus
      plantarum codes one such protein and is adjacent to the citrulline biosynthesis
      operon argCJBDF, a situation also found in Lactococcus lactis. This gene is well
      conserved among L. plantarum species, and 1 isolate out of 24 harbored two ccl
      copies. Northern hybridization with a ccl probe revealed two arginine-repressed
      transcripts with sizes corresponding to the predicted argCJBDF-ccl operon and the
      ccl gene alone. Transcription start sites of both transcripts were characterized.
      Four different 5' ends were mapped at the argF-ccl intergenic region, resulting
      from either regulated transcription initiation or maturation of the transcripts.
      Transcriptional ccl-gusA gene fusion confirmed the promoter activity of the argF
      ccl intergenic region. Thus, the ccl gene is arginine-repressed and transcribed
      both monocistronically and polycistronically in the argCJBDF-ccl operon. The ccl
      gene is not essential in L. plantarum, because a ccl gene deletion was obtained
      in strain CCM 1904. Although no functions were found in the tested laboratory
      conditions, the Ccl-like proteins may play a role in environmental conditions of
      life.

PMID- 15864551
TI  - Effect of cytochrome P450 inhibitors and anticonvulsants on the acute toxicity of
      acrylonitrile.
AB  - Some of the more striking expressions of toxicity are the tremors and seizures
      observed approximately 100 min after exposure of rats to an acutely toxic dose of
      acrylonitrile (AN). These early events are followed by a second wave of severe
      clonic convulsions that occur just prior to death at about 3-4 h. For AN, at
      least two chemical entities could produce these toxic effects, namely the parent
      AN molecule, the metabolically-released cyanide, or both. Which of these two
      agents is responsible for each of the symptoms of acute intoxication is not
      known. To help dissect the toxicity, it was anticipated that an effective
      inhibitor of the oxidative metabolism of AN to cyanide could help us to
      understand which toxic symptoms might be associated with each agent. Three
      inhibitors of oxidative metabolism were tested, namely SKF-525A, 1
      benzylimidazole and metyrapone and one alternative substrate, ethanol. As
      compared to SKF-525A and metyrapone, both 1-benzylimidazole and ethanol were
      highly effective in reducing blood cyanide levels to insignificant levels in rats
      treated with an LD90 dose of AN. In addition, both agents abolished the early
      seizure activity, suggesting that this first phase of seizures is due to cyanide
      and not the parent molecule. 1-Benzylimidazole did not prevent the severe clonic
      convulsive phase preceding death, suggesting that these terminal convulsions are
      due to the toxic effects of the parent AN molecule. The CNS depressant ethanol
      was only partially effective in attenuating the terminal convulsions. None of
      these agents affected the incidence of AN-induced mortality, clearly establishing
      that, even in the absence of cyanide, the parent AN molecule is acutely toxic.
      The partial effectiveness of ethanol suggested that anticonvulsants might be of
      benefit. Both phenobarbital and phenytoin protected rats from both the early and
      terminal convulsions, while valproic acid was ineffective. These effects were not
      related to a reduction in blood cyanide levels but rather due to their inherent
      anticonvulsant activity.

PMID- 15864552
TI  - Chemoprevention of acrylamide toxicity by antioxidative agents in rats--effective
      suppression of testicular toxicity by phenylethyl isothiocyanate.
AB  - The efficacies of N-acetylcysteine (NAC), phenylethyl isothiocyanate (PEITC), and
      1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ) at preventing the neurotoxicity and
      testicular toxicity of acrylamide (ACR) were investigated in rats. To this end,
      Sprague-Dawley males were given 0.02% ACR in drinking water, with or without 1%
      NAC, 0.5% PEITC or 0.1% HTHQ in the diet for four weeks. A group of untreated
      controls was also included in the study. All ACR-treated animals exhibited
      progressive neurotoxicity as judged by gait scores, and among the chemicals co
      administered, only HTHQ caused any suppression by the end of the experiment, and
      this was slight. The severity of the neurotoxicity, as judged by axonal
      degeneration in the spinal gracile fasciculus and sciatic nerve (distal portion)
      and aberrant dot-like synaptophysin immunoreactivity, reflecting nerve terminal
      degeneration in the cerebellar molecular layer, was not clearly reduced by co
      administration of HTHQ, NAC or PEITC either. ACR-induced sciatic nerve axon
      atrophy was marginally and non-significantly reduced by HTHQ. In contrast, in
      terms of ACR-induced testicular toxicity, exfoliation of spermatids into
      seminiferous lumen was clearly reduced by co-administered PEITC and was
      marginally reduced by co-administered HTHQ. These antioxidative agents may
      therefore reduce/prevent ACR-induced toxicity, at least in the testes.

PMID- 15864553
TI  - Behavioural and pharmacological magnetic resonance imaging assessment of the
      effects of methylphenidate in a potential new rat model of attention deficit
      hyperactivity disorder.
AB  - RATIONALE: The psychomotor stimulant methylphenidate is used in the treatment of
      attention deficit hyperactivity disorder (ADHD). Whereas the mechanism is not
      fully understood it is suggested to involve restoration of impaired dopamine
      function found in ADHD. OBJECTIVES: The aim of this study was to determine the
      effects of methylphenidate on brain region activation in vivo using
      pharmacological magnetic resonance imaging (phMRI) in a potential rat model of
      ADHD. METHODS: Rats were treated bi-daily [from postnatal day (PND) 24] for 4
      days with the dopamine re-uptake inhibitor GBR 12909 (30 mg/kg i.p) or vehicle
      (control). On PND 57 rats were administered methylphenidate (4 mg/kg i.p) and
      locomotor activity measured. In a separate group of animals, blood oxygen level
      dependent (BOLD) response was measured using phMRI to determine changes in brain
      region activation produced by methylphenidate (4 mg/kg i.p.) in GBR 12909
      pretreated or control rats. RESULTS: Methylphenidate produced a greater locomotor
      stimulant response in controls compared with GBR 12909 rats. Pretreatment with
      GBR 12909 reduced the BOLD response produced by methylphenidate compared with
      that in control animals. The main effects of methylphenidate on the BOLD response
      were seen in the caudate, frontal cortex, hippocampus and hypothalamus.
      CONCLUSIONS: Short-term treatment with GBR 12909 in young rats causes long-term
      changes in dopaminergic systems, altering the methylphenidate-induced behavioural
      response and brain region activation compared with that in vehicle-pretreated
      rats. The results further support the view that altered dopaminergic function may
      be an important factor in ADHD and the value of animal models with this
      functional neurochemical deficit.

PMID- 15864554
TI  - GABA-benzodiazepine receptor function in alcohol dependence: a combined 11C
      flumazenil PET and pharmacodynamic study.
AB  - RATIONALE: Gamma-aminobutyric acid (GABA)-benzodiazepine receptor function is
      hypothesised to be reduced in alcohol dependence. OBJECTIVES: We used positron
      emission tomography (PET) with [11C]flumazenil, a non-selective tracer for brain
      GABA-benzodiazepine (GABA-BDZ) receptor binding, to determine in vivo the
      relationship between BDZ receptor occupancy by an agonist, midazolam, and its
      functional effects. METHODS: Abstinent male alcohol dependent subjects underwent
      [11C]flumazenil PET to measure occupancy of BDZ receptors by midazolam whilst
      recording its pharmacodynamic effects on behavioural and physiological measures.
      Rate constants describing the exchange of [11C]flumazenil between the plasma and
      brain compartments were derived from time activity curves. RESULTS: A 50%
      reduction in electroencephalography (EEG)-measured sleep time was seen in the
      alcohol dependent group despite the same degree of occupancy by midazolam as seen
      in the control group. The effects of midazolam on other measures of
      benzodiazepine receptor function, increasing EEG beta1 power and slowing of
      saccadic eye movements, were similar in the two groups. No differences in
      midazolam or flumazenil metabolism were found between the groups. CONCLUSIONS: In
      summary, our study suggests that alcohol dependence in man is associated with a
      reduced EEG sleep response to the benzodiazepine agonist, midazolam, which is not
      explained by reduced BDZ receptor occupancy, and is consistent with reduced
      sensitivity in this measure of GABA-BDZ receptor function in alcohol dependence.
      The lack of change in other functional measures may reflect a differential
      involvement of particular subtypes of the GABA-BDZ receptor.

PMID- 15864555
TI  - Susceptibility to conditioned place preference induced by addictive drugs in mice
      of the C57BL/6 and DBA/2 inbred strains.
AB  - RATIONALE: In previous studies, we have demonstrated that mice of the inbred
      strain C57BL/6J (C57) are more susceptible to amphetamine-induced conditioned
      place preference (CPP) than DBA/2J (DBA) mice. Moreover, we also observed
      parallel strain differences for the locomotor-stimulant effects of the drug.
      However, other studies have reported either no difference or opposite strain
      differences for cocaine- and morphine-induced CPP as well as for the locomotor
      effects of these drugs, suggesting that amphetamine-related behavioral phenotypes
      might depend on a specific pharmacological action of the psychostimulant.
      OBJECTIVES: This study was aimed at testing strain differences for cocaine- and
      morphine-related behavioral phenotypes in the same experimental protocol and
      conditions previously used for amphetamine. METHODS: C57 and DBA mice were tested
      for CPP induced by cocaine (0, 5, 10, and 20 mg/kg) and morphine (0, 5, 7.5, and
      10 mg/kg). Locomotor activity data were simultaneously obtained by measuring
      distance moved during all different CPP phases and unconditioned locomotor
      activity, behavioral sensitization and conditioned hyperactivity were measured
      together with CPP. RESULTS: (a) Either cocaine or morphine promoted significant
      CPP at lower doses in C57 than in DBA mice; (b) only drug-trained C57 mice showed
      a significant CPP compared with the control group; and (c) only C57 mice showed
      dose-dependent effects of cocaine on CPP. Moreover, there was no relationship
      between drug-induced CPP and locomotion. CONCLUSIONS: The results demonstrate
      that C57 and DBA mice differ in their sensitivity to cocaine- and morphine
      induced CPP and suggest that the two strains differ in sensitivity to the
      positive incentive properties of drugs of abuse.

PMID- 15864556
TI  - Examining the neural targets of the AMPA receptor potentiator LY404187 in the rat
      brain using pharmacological magnetic resonance imaging.
AB  - RATIONALE: Drugs that enhance alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropanoic
      acid (AMPA) receptor-mediated glutamatergic transmission, such as the AMPA
      receptor potentiator LY404187, may form treatment strategies for disorders of
      cognition, learning and memory. OBJECTIVES: Pharmacological magnetic resonance
      imaging (phMRI) uses blood oxygenation level dependent (BOLD) contrast as a
      marker of neuronal activity and allows dynamic non-invasive in vivo imaging of
      the effects of CNS-active compounds. This study used phMRI to examine the effects
      of LY404187 in the rat brain. METHOD: Groups of Sprague Dawley rats (n=7) were
      anaesthetised and placed in a 4.7 Tesla superconducting magnet before receiving
      an acute dose of LY404187 (0.5 mg/kg s.c.), either alone or after pretreatment
      with the selective AMPA/kainate antagonist LY293558 (15 mg/kg s.c.), or LY293558
      alone (15 mg/kg s.c.). Brain images were acquired for each subject every minute
      for 180 min. These volumes were extensively pre-processed before being analysed
      for changes in BOLD contrast. RESULTS: LY404187 produced significant increases in
      BOLD contrast in brain regions including the hippocampus, lateral and medial
      habenulae and superior and inferior colliculi. These changes were blocked by
      LY293558. When administered alone, LY293558 caused widespread decreases in BOLD
      contrast. CONCLUSIONS: The known actions of LY404187 suggest the observed BOLD
      signal increases reflect increases in excitatory neurotransmission. The decreases
      in signal following LY293558 alone are harder to interpret and are discussed in
      terms of the negative BOLD response. This study provides the first evidence that
      the effects of AMPA receptor-mediating compounds can be observed using phMRI.

PMID- 15864557
TI  - The phenylephrine blood pressure clamp in pharmacologic magnetic resonance
      imaging: reduction of systemic confounds and improved detectability of drug
      induced BOLD signal changes.
AB  - RATIONALE: Peripheral physiologic changes accompany many central pharmacologic
      manipulations and can interact with brain activity and cerebral perfusion in
      complex ways. This considerably complicates the interpretation of drug-induced
      brain activity changes. OBJECTIVES: To evaluate a method whereby drug-induced
      blood pressure (BP) changes are prevented. METHODS: A continuously adjusted
      infusion of the peripheral vasoconstrictor phenylephrine (PEP) was used to
      counter-regulate BP changes elicited by application of the dopamine receptor
      agonist apomorphine (APO) in the rat. Central effects of APO were measured using
      pharmacologic magnetic resonance imaging (phMRI) with blood oxygenation level
      dependent (BOLD) contrast at a field strength of 7 T. RESULTS: Compared to a
      NOPEP control group, the PEP blood pressure clamp successfully prevented BP
      changes and improved the detectability of central APO effects. Moreover, APO
      induced central changes no longer correlated with BP time courses. CONCLUSIONS:
      The method is suitable for isolating central drug effects from peripherally
      originating (BP) confounds in high-field functional magnetic resonance imaging
      (fMRI) studies. It may also be useful in fMRI studies of autonomic regulation,
      cognition, and emotion if the experimental manipulation entails BP changes.

PMID- 15864558
TI  - Paroxetine is effective in desensitizing 5-HT1A receptor function in adult
      offspring exposed prenatally to cocaine.
AB  - RATIONALE: Desensitization of postsynaptic 5-HT(1A) receptors may be responsible
      for the therapeutic effectiveness of serotonin selective uptake inhibitors
      (SSRIs). As prenatal cocaine exposure produces long-term deficits in 5-HT neurons
      in offspring, it may alter the ability of postsynaptic 5-HT(1A) receptors to be
      desensitized by chronic paroxetine. OBJECTIVES: The aim of the study is to
      determine (1) prenatal cocaine-induced changes in 5-HT(1A) receptor function and
      (2) the effectiveness of chronic treatment with paroxetine to produce 5-HT(1A)
      receptor desensitization in adult offspring exposed to cocaine in utero. METHODS:
      Pregnant rats received saline or (-)cocaine (15 mg/kg, s.c.) twice daily from
      gestational days 13 through 20. Adult male offspring from each of prenatal groups
      were treated with saline or paroxetine (10 mg/kg/day; i.p.) for 14 days. Eighteen
      hours post-treatment, rats were challenged with saline or the 5-HT(1A) receptor
      agonist (+)8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.04 or 0.2 mg/kg,
      s.c.). Plasma oxytocin, adrenocorticotropic hormone (ACTH), corticosterone, renin
      and prolactin were determined. RESULTS: Prenatal cocaine exposure did not alter 5
      HT(1A) receptor-mediated neuroendocrine responses. Paroxetine treatment
      desensitized 5-HT(1A) receptor-mediated increases in oxytocin, ACTH and
      corticosterone to a comparable extent in all offspring and reduced the E(max) for
      ACTH only in prenatal cocaine-exposed offspring. Cortical [(3)H]-8-OH-DPAT- or
      [(3)H]-WAY100635-labeled 5-HT(1A) receptors were unaltered by prenatal cocaine or
      subsequent paroxetine treatment. CONCLUSIONS: Postsynaptic 5-HT(1A) receptor
      function is unaltered by prenatal cocaine exposure and paroxetine can effectively
      desensitize 5-HT(1A) receptor function in adult cocaine-exposed offspring. These
      data suggest that paroxetine may be clinically effective in treating mood
      disorders in adults exposed in utero to cocaine.

PMID- 15864559
TI  - Effects of quipazine and m-chlorophenylbiguanide (m-CPBG) on temporal
      differentiation: evidence for the involvement of 5-HT2A but not 5-HT3 receptors
      in interval timing behaviour.
AB  - RATIONALE: Temporal differentiation refers to animals' ability to regulate their
      behaviour during an ongoing interval. Striatal dopaminergic mechanisms are
      purported to be involved in temporal differentiation, and recent evidence also
      implicates 5-hydroxytryptaminergic (5-HTergic) mechanisms, possibly mediated by 5
      HT(2A) receptors. There is evidence that 5-HT(3) receptors contribute to the
      regulation of dopamine release in the basal ganglia; however, it is not known
      whether 5-HT(3) receptor stimulation can influence temporal differentiation.
      OBJECTIVE: We examined the effects of a selective 5-HT(3) receptor agonist m
      CPBG, a mixed 5-HT(2A/3) receptor agonist quipazine, and selective 5-HT(3) and 5
      HT(2A) receptor antagonists (MDL-72222 and ketanserin, respectively) on temporal
      differentiation in a free-operant psychophysical procedure. METHODS: Twenty-four
      rats were trained to respond on two levers (A and B) under a free-operant
      psychophysical schedule, in which sucrose reinforcement (0.6 M: , 50 microl) was
      provided intermittently for responding on A during the first half and on B during
      the second half of 50-s trials. Logistic psychometric functions were fitted to
      the relative response rate data [percent responding on B (%B) vs time from trial
      onset (t)], and quantitative indices of timing performance [T (50) (value of t
      corresponding to %B=50), Weber fraction, and mean time of switching from A to B,
      S (50)] were derived. RESULTS: Quipazine (0.5, 1, and 2 mg kg(-1)) altered timing
      performance, dose-dependently reducing T (50) and S (50); m-CPBG (2.5, 5, and 10
      mg kg(-1)) had no significant effect. The effect of quipazine was antagonized by
      ketanserin (2 mg kg(-1)), but not by MDL-72222 (1 mg kg(-1)). CONCLUSIONS: The
      present results provide no evidence for the involvement of 5-HT(3) receptors in
      temporal differentiation and indicate that the effect of quipazine on performance
      was mediated by 5-HT(2A) receptor stimulation. The results are consistent with
      previous evidence for the involvement of 5-HT(2A) receptors in interval timing
      behaviour.

PMID- 15864560
TI  - GABAergic dysfunction in schizophrenia: new treatment strategies on the horizon.
AB  - RATIONALE: Cortical gamma-aminobutyric acid (GABA)ergic neurons contribute to the
      orchestration of pyramidal neuron population firing as follows: (1) by releasing
      GABA on GABA(A) and GABA(B) receptors, (2) by releasing reelin in the proximity
      of integrin receptors located on cortical pyramidal neuron dendritic spines, and
      (3) through reelin contributing to the regulation of dendritic spine plasticity
      by modulating dendritic resident mRNA translation. In schizophrenia (SZ) and
      bipolar (BP) postmortem brains, the downregulation of mRNAs encoding glutamic
      acid decarboxylase 67 (GAD(67)) and reelin decreases the cognate proteins
      coexpressed in prefrontal cortex (PFC) GABAergic neurons. This finding has been
      replicated in several laboratories. Such downregulation suggests that the
      neuropil hypoplasticity found in the PFC of SZ and BP disorder patients may
      depend on a downregulation of GABAergic function, which is associated with a
      decrease in reelin secretion from GABAergic neuron axon terminals on dendrites,
      somata, or axon initial segments of pyramidal neurons. Indirectly, this GABAergic
      neuron downregulation may play a key role in the expression of positive and
      negative symptoms of SZ and BP disorders. OBJECTIVES: The above described
      GABAergic dysfunction may be addressed by pharmacological interventions to treat
      SZ and BP disorders using specific benzodiazepines (BZs), which are devoid of
      intrinsic activity at GABA(A) receptors including alpha(1) subunits but that act
      as full positive allosteric modulators of GABA action at GABA(A) receptors
      containing alpha(2), alpha(3), or alpha(5) subunits. These drugs are expected to
      enhance GABAergic signal transduction without eliciting sedation, amnesia, and
      tolerance or dependence liabilities. RESULTS AND CONCLUSIONS: BZs, such as
      diazepam, although they are efficient in equilibrating GABA(A) receptor signal
      transduction in a manner beneficial in the treatment of positive and negative
      symptoms of SZ, may not be ideal drugs, because by mediating a full positive
      allosteric modulation of GABA(A) receptors containing the alpha(1) subunit, they
      contribute to sedation and to the development of tolerance after even a brief
      period of treatment. In contrast, other BZ-binding site ligands, such as 6
      (2bromophenyl)-8-fluoro-4H-imidazo [1,5-a][1,4] benzodiazepine-3-carboxamide
      (imidazenil), which fail to allosterically and positively modulate the action of
      GABA at GABA(A) receptors with alpha(1) subunits but that selectively
      allosterically modulate cortical GABA(A) receptors containing alpha(5) subunits,
      contribute to the anxiolytic, antipanic, and anticonvulsant actions of these
      ligands without producing sedation, amnesia, or tolerance. Strong support for the
      use of imidazenil in psychosis emerges from experiments with reeler mice or with
      methionine-treated mice, which express a pronounced reelin and GAD(67)
      downregulation that is also operative in SZ and BP disorders. In mice that model
      SZ symptoms, imidazenil increases signal transduction at GABA(A) receptors
      containing alpha(5) subunits and contributes to the reduction of behavioral
      deficits without producing sedation or tolerance liability. Hence, we suggest
      that imidazenil may be considered a prototype for a new generation of positive
      allosteric modulators of GABA(A) receptors, which, either alone or in combination
      with neuroleptics, should be evaluated in GABAergic dysfunction operative in the
      treatment of SZ and BP disorders with psychosis.

PMID- 15864561
TI  - Differential involvement of serotonin and dopamine systems in cost-benefit
      decisions about delay or effort.
AB  - RATIONALE: Although tasks assessing the role of dopamine in effort-reward
      decisions are similar to those concerned with the role of serotonin in impulsive
      choice in that both require analysis of the costs and benefits of possible
      actions, they have never been directly compared. OBJECTIVES: This study
      investigated the involvement of serotonin and dopamine in two cost-benefit
      paradigms, one in which the cost was delay and the other in which it was physical
      effort. METHODS: Sixteen rats were trained on a T-maze task in which they chose
      between high and low reward arms. In one version, the high reward arm was
      obstructed by a barrier, in the other, delivery of the high reward was delayed by
      15 s. Serotonin and dopamine function were manipulated using systemic pCPA and
      haloperidol injections, respectively. RESULTS: Haloperidol-treated rats were less
      inclined either to exert more effort or to countenance a delay for a higher
      reward. pCPA had no effect on the performance of the rats on the effortful task,
      but significantly increased the rats' preference for an immediate but smaller
      reward. All animals (drug treated and controls) chose the high reward arm on the
      majority of trials when the delay or effort costs were matched in both high and
      low reward arms. CONCLUSION: A dissociation was found between the
      neurotransmitter systems involved in different types of cost-benefit decision
      making. While dopaminergic systems were required for decisions about both effort
      and delay, serotonergic systems were only needed for the latter.

PMID- 15864562
TI  - Corticotropin-releasing factor: effect on cerebral blood flow in physiologic and
      ischaemic conditions.
AB  - The expression of corticotrophin-releasing factor (CRF) receptors in cerebral
      arteries and arterioles suggests that CRF may modulate cerebral blood flow (CBF).
      In the present study, the effects of CRF, CRF-like peptides and the CRF broad
      spectrum antagonist DPhe-CRF on CBF have been investigated under normal
      physiologic conditions and in the margins of focal ischaemic insult. The
      experiments were carried out in anaesthetised and ventilated rats. Changes in CBF
      after subarachnoid microapplication of CRF and related peptides were assessed
      with a laser-Doppler flowmetry (LDF) probe. In the ischaemic animals, agents were
      injected approximately 60 minutes after permanent middle cerebral artery
      occlusion (MCAo). Microapplication of CRF and related peptides in normal rats
      into the subarachnoid space produced sustained concentration-dependent increases
      in CBF. This effect was attenuated by co-application with DPhe-CRF, which did not
      alter CBF itself. A second microapplication of CRF 30 min after the first failed
      to produce increases in CBF in normal animals. Microapplication of CRF in the
      subarachnoid space overlying the ischaemic cortex effected minor increases in CBF
      whereas D-Phe-CRF had no significant effect on CBF. Activation of the CRF
      peptidergic system increases CBF in the rat. Repeated activation of CRF receptors
      results in tachyphylaxis of the vasodilator response. CRF vasodilator response is
      still present after MCAo in the ischaemic penumbra, suggesting that the CRF
      peptidergic system may modulate CBF in ischaemic stroke.

PMID- 15864563
TI  - An fMRI study of optokinetic nystagmus and smooth-pursuit eye movements in
      humans.
AB  - Both optokinetic nystagmus (OKN) and smooth-pursuit eye movements (SPEM) are
      subclasses of so-called slow eye movements. However, optokinetic responses are
      reflexive whereas smooth pursuit requires the voluntary tracking of a moving
      target. We used functional magnetic resonance imaging (fMRI) to determine the
      neural basis of OKN and SPEM, and to uncover whether the two underlying neural
      systems overlap or are independent at the cortical level. The results showed a
      largely overlapping neural circuitry. A direct comparison between activity during
      the execution of OKN and SPEM yielded no oculomotor-related area exclusively
      dedicated to one or the other eye movement type. Furthermore, the performance of
      SPEM evoked a bilateral deactivation of the human equivalent of the
      parietoinsular vestibular cortex. This finding might indicate that the
      reciprocally inhibitory visual-vestibular interaction involves not only OKN but
      also SPEM, which are both linked with the encoding of object-motion and self
      motion. Moreover, we could show differential activation patterns elicited by look
      nystagmus and stare-nystagmus. Look-nystagmus is characterized by large
      amplitudes and low-frequency resetting eye movements rather resembling SPEM. Look
      nystagmus evoked activity in cortical oculomotor centers. By contrast, stare
      nystagmus is usually characterized as being more reflexive in nature and as
      showing smaller amplitudes and higher frequency resetting eye movements. Stare
      nystagmus failed to elicit significant signal changes in the same regions as look
      nystagmus/SPEM. Thus, less reflexive eye movements correlated with more
      pronounced signal intensity. Finally, on the basis of a general investigation of
      slow eye movements, we were interested in a cortical differentiation between
      subtypes of SPEM. We compared activity associated with predictable and
      unpredictable SPEM as indicated by appropriate visual cues. In general,
      predictable and unpredictable SPEM share the same neural network, yet information
      about the direction of an upcoming target movement reduced the cerebral activity
      level.

PMID- 15864564
TI  - Human whole-body reaching in normal gravity and microgravity reveals a strong
      temporal coordination between postural and focal task components.
AB  - Previous experiments by our group in normal gravity (1 G) have revealed spatial
      relationships between postural and focal components of whole-body reaching and
      pointing movements. We suggested that these relationships could be explained
      partly through the use of gravity to displace the CoM and attain the object or
      target position. In this study we compared human whole-body reaching in 1 G and
      microgravity (0 G) in order to more fully investigate how gravity contributes to
      strategies adopted for task execution and to determine possible invariant
      temporal relationships between multiple segments. Whole-body reaching movements
      made from the standing position in two experimental conditions of execution speed
      (naturally paced and as fast as possible) were recorded during periods of 1 G and
      0 G in parabolic flight. Overall, at each speed of reaching, movement times were
      significantly slower when performed in 0 G than in 1 G for two of the three
      subjects, but all subjects were able to produce significantly faster movements in
      0 G than in 1 G. Despite similar general trends across subjects observed in 1 G,
      angular displacements of reaching movements performed in 0 G differed greatly
      between subjects. There were changes at all joints, but above all at the shoulder
      and the ankle. However, despite a high intersubject and intratrial variability in
      0 G, in both gravity conditions all subjects demonstrated times to peak
      curvilinear velocity for the finger (end effector) and the whole-body centre of
      mass (CoM) that coincided, regardless of the speed of execution. Moreover, cross
      correlations between multiple segment curvilinear velocities and those of the CoM
      revealed tight, highly correlated temporal relationships between segments
      proximal to the CoM (which was expected). However, for more distal segments, the
      correlations were weaker, and the movements lagged behind movements of the CoM.
      The major and most interesting finding of this study was that although the finger
      was the most distal within the segment chain, with respect to the CoM, it was
      highly correlated with the CoM (0.99--0.98, all conditions) and with no time lag.
      Despite the large intersubject and inter-environmental variability recorded in
      this study, temporal relationships between postural task components (CoM
      displacements) and those of the focal movement (end-effector trajectory) were
      consistently conserved.

PMID- 15864565
TI  - Walking is more like catching than tapping: gait in the elderly as a complex
      cognitive task.
AB  - Walking is generally viewed as an automated, over-learned, rhythmic motor task
      and may even be considered the lower-limb analog of rhythmic finger tapping,
      another automated motor task. Thus, one might hypothesize that walking would be
      associated with a simple rhythmic task like tapping rather than with a complex
      motor task like catching. Surprisingly, however, we find that among older adults,
      routine walking has more in common with complex motor tasks, like catching a
      moving object, than it does with tapping. Tapping performance, including both the
      average tapping interval and the variability of tapping interval, was not
      significantly associated with any gait parameter (gait speed, average stride time
      and stride time variability). In contrast, catch game performance was
      significantly associated with measures of walking, suggesting that walking is
      more like catching than it is like tapping. For example, participants with a
      higher gait speed tended to have lower times to first move when catching, better
      catching accuracy, and less catching errors. Stride time variability was
      significantly associated with each of the measures of catching. Participants with
      a lower stride time variability (a more steady gait) had better catching
      accuracy, lower time to first move, fewer direction changes when moving the
      cursor to catch the falling object, and less catching errors. To understand this
      association, we compared walking performance to performance on the Stroop test, a
      classic measure of executive function, and tests of memory. Walking was
      associated with higher-level cognitive resources, specifically, executive
      function, but not with memory or cognitive function in general. For example, a
      lower (better) stride time variability was significantly associated with higher
      (better) scores on the Stroop test, but not with tests of memory. Similarly, when
      participants were stratified based on their performance on the Stroop test and
      tests of memory, stride time variability was dependent on the former, but not the
      latter. These findings underscore the interconnectedness of gait and cognitive
      function, indicate that even routine walking is a complex cognitive task that is
      associated with higher-level cognitive function, and suggest an alternative
      approach to the treatment of gait and fall risk in the elderly.

PMID- 15864566
TI  - Differential effects of target probability on saccade latencies in gap and
      warning tasks.
AB  - Saccade latencies are significantly reduced by extinguishing a foveal fixation
      stimulus before the appearance of a saccade target. It has been shown recently
      that this "fixation offset effect" (FOE) can be modulated by varying target
      probability. Cortico-collicular top-down effects have been assumed to mediate
      this strategic FOE modulation. Here, we have investigated strategic FOE
      modulation in 14 healthy human subjects performing gap and warning tasks. In the
      former task, the central fixation point was extinguished 200 ms before target
      onset. In the latter task, the central fixation point changed its colour 200 ms
      before target onset, but remained illuminated until the target appeared. Target
      probability was varied block-wise between 25 and 75%. In both tasks, mean
      latencies decreased with increasing target probability. However, in contrast with
      what can be expected from preceding studies, we found no differential modulation
      of mean latencies by target probability between tasks. Instead, we observed
      differential probability-dependent changes in latency distributions. In the gap
      task, discrete changes of saccade latencies were found, with a probability
      dependent change in frequency of express and regular latencies. By contrast, in
      the warning task a shift of the entire latency distribution towards longer
      latencies with low target probability was found. We conclude that strategic
      modulation of saccade latencies by target probability may be mediated by two
      distinct neural mechanisms. Selection of either mechanism seems to depend
      critically on activation of the fixation system.

PMID- 15864567
TI  - Time series analysis of magnetoencephalographic data during copying.
AB  - We used standard time series modeling to analyze magnetoencephalographic (MEG)
      data acquired during three tasks. Each task lasted 45 s, for a total data
      acquisition period of 135 s. Ten healthy human subjects fixated their eyes on a
      central blue point for 45 s (fixation only, "F" task). Then a pentagon (visual
      template) appeared surrounding the fixation point which simultaneously became red
      (fixation + template, "FT" task). After 45 s, the fixation point changed to
      green, which was the "go" signal for the subjects to begin continuously copying
      the pentagon for 45 s using a joystick and without visual feedback of their
      movement trajectory (fixation + template + copying, "FTC" task). MEG data were
      acquired continuously from 248 axial gradiometers at a sampling rate of 1017.25
      Hz. After removal of cardiac artifacts and rejection of records with eyeblink
      artifacts, a Box-Jenkins autoregressive integrative moving average (ARIMA)
      analysis was applied to the unsmoothed, unaveraged MEG time series for model
      identification and estimation within 25 time lags (approximately 25 ms). We found
      that an ARIMA model of 25th order autoregressive, first order differencing, and
      first order moving average (p=25, d=1, q=1) adequately modeled the series and
      yielded residuals practically stationary with respect to their mean, variance,
      and autocorrelation structure. These "prewhitened" residuals were then used for
      assessing pairwise associations between series using crosscorrelation analysis
      with +/-25 time lags (approximately +/-25 ms). The cross-correlograms thus
      obtained revealed rich and consistent patterns of interactions between series
      with respect to positive and/or negative correlations. The overall prevalence of
      these patterns was very similar in the three tasks used, and, for particular
      sensor pairs, they tended to be preserved across tasks.

PMID- 15864568
TI  - Spatial and non-spatial auditory processing in the lateral intraparietal area.
AB  - We tested the responses of neurons in the lateral parietal area (area LIP) for
      their sensitivity to the spatial and non-spatial attributes of an auditory
      stimulus. We found that the firing rates of LIP neurons were modulated by both of
      these attributes. These data indicate that, while area LIP is involved in spatial
      processing, non-spatial processing is not restricted to independent channels.

PMID- 15864569
TI  - Self-generated saccades do not modify the gain of adapted reactive saccades.
AB  - The gain of reactive saccades was manipulated in 17 subjects using a target-jump
      paradigm. Following adaptation three sub-groups were formed: (1) rest 15 min in
      the dark, eyes closed; (2) perform self-generated saccades for 15 min; (3)
      perform reactive saccades for 15 min. The series of saccades were the same in
      groups 2 and 3 (amplitude, sequence), except that group 3 performed fewer
      saccades (same number as the lowest number of saccades performed by one subject
      in group 2). Neither the rest period nor the series of self-generated saccades
      affected the adapted gain. The series of reactive saccades generated, by
      contrast, quick de-adaptation. These results support the conclusion that the gain
      of self-generated and reactive saccades is independently controlled.

PMID- 15864570
TI  - Changes in the defined daily dose; CYP2D6/CYP3A metabolism as an indicator for
      dose-setting problems.
AB  - OBJECTIVE: Interindividual variability is common at all stages of drug
      absorption, distribution, pharmacodynamics, metabolism and elimination. In this
      study, we focused on two enzymes involved in phase-I drug metabolism as markers
      of pharmacological variability: the CYP3A and CYP2D6 subsystems of cytochrome
      P450. The main aim of our study was to determine whether substrate drugs for
      CYP2D6 and/or CYP3A enzymes, showing high interindividual matabolic variability,
      are more prone to postmarketing adjustments of defined daily dose (DDD). METHODS:
      A case-control design was used. We identified all DDD changes between 1982 and
      May 2004 through the website of the WHO Collaborating Centre for Drug Statistics
      Methodology. Cases were drugs with a DDD change and controls were other drugs
      with unchanged DDDs. Information about metabolism pathway, introduction year,
      literature exposure and administration route was retrieved. RESULTS: We included
      88 cases and 176 controls. Of the 88 cases, 51 were dosage decreases (58.0%).
      Overall, DDD changes were not associated with CYP2D6/CYP3A metabolism (OR 1.92;
      95%CI 0.78-4.72). However, DDD decreases were associated with CYP2D6/CYP3A
      metabolism (OR 3.21; 95%CI 1.25-8.26). Adjusting for introduction year weakened
      this effect (OR 2.78; 95%CI 0.98-7.90). CONCLUSION: Our study indicates that
      CYP2D6 and CYP3A substrates are more likely to require a DDD decrease after
      granting of market authorisation. However, this effect was diminished by
      adjusting for period of introduction. The implication of this finding is that
      variability indicators, as is demonstrated in this study for CYP2D6/CYP3A
      metabolism, can exert their influence on a wide variety of drug measures, such as
      the DDD.

PMID- 15864571
TI  - General practitioners prefer prescribing indicators based on detailed information
      on individual patients: a Delphi study.
AB  - OBJECTIVE: To assess the face validity of both simple and advanced quality
      indicators for prescribing in general practice. METHODS: In a three-round Delphi
      study, 100 randomly selected general practitioners (GPs) in Denmark rated 18
      indicators for prescribing of non-steroidal anti-inflammatory drugs. All
      indicators were based on prescription register data and focused on different
      prescribing aspects. Advanced indicators contained information at the patient
      level, viz. age, sex and history of drug use, while simple indicators only used
      drug statistics at practice level. Indicators were rated on a nine-point Likert
      scale. Consensus among GPs was defined as interquartile ranges of three or less.
      A median rating of 7-9 was interpreted as face validity and a median rating of 1
      3 as no face validity. RESULTS: Participation in the study was accepted by 44 GPs
      and 37 completed all three rounds. Three indicators based on patient level data
      and focusing on adverse effects were assessed to have face value. One indicator
      focusing on costs and based on practice level data was considered unsuitable for
      evaluating the quality of prescribing. Consensus was not reached for the
      remaining indicators. CONCLUSIONS: GPs do not regard simple indicators based on
      aggregated data at practice level as suitable for evaluating the prescribing
      quality in general practice, but prefer indicators that rest on clinical data at
      the patient level.

PMID- 15864572
TI  - Regulation by macromolecules of calcium oxalate crystal aggregation in stone
      formers.
AB  - Based on the structure of kidney stones, it is likely that they form as
      aggregations of preformed crystals, mostly calcium oxalate monohydrate (COM). In
      this study, we examined the ability of a macromolecular mixture isolated from the
      urine of normal individuals and stone formers to inhibit aggregation of preformed
      COM seed crystals in a simple ionic solution using measurements of changes in the
      particle size distribution (PSD) of preformed COM crystal aggregates. We also
      examined the effect in this assay of a number of synthetic homopolymers,
      naturally occurring urine macromolecules, and binary mixtures thereof. The
      macromolecular mixtures from urine of normals and most stone formers reduced the
      degree of aggregation of the seed crystals, whereas 22% of stone former urine
      macromolecules either did not disaggregate or actually promoted further
      aggregation. Stone formers within one family shared this property, but a non
      stone forming sibling did not. Polyanions, either synthetic or naturally
      occurring, induced disaggregation to an extent similar to that exhibited by
      normal urine macromolecules, while polycations had no effect on the PSD. However,
      mixing a polyanion, either poly-aspartate or osteopontin, with the polycation
      poly-arginine, changed their behavior from disaggregation to aggregation
      promotion. The disaggregating behavior of normal urinary macromolecules provides
      a defense against aggregation, but a minority of stone forming individuals lacks
      this defense, which may contribute to stone formation.

PMID- 15864573
TI  - Tuberculous splenic abscess in a neonate with thrombocytopenia.
AB  - We present a case of a premature neonate who presented with anemia and persistent
      thrombocytopenia. The patient was ultimately diagnosed with disseminated
      tuberculosis. Initial sonographic evaluation of the abdomen revealed a
      heterogeneous but predominantly hypoechoic spleen; there was subsequent evolution
      of a splenic abscess. The patient was treated medically with anti-tubercular
      drugs. Follow-up post-treatment sonograms of the spleen showed diminution of the
      abscess and the evolution of multiple calcifications compatible with calcified
      granulomas. This case is an unusual presentation of tuberculosis in an infant
      with splenic abscess associated with thrombocytopenia and anemia.

PMID- 15864574
TI  - Solid-pseudopapillary neoplasm of the pancreas: radiological-pathological
      correlation.
AB  - We report two cases to demonstrate the imaging features of solid-pseudopapillary
      neoplasm of the pancreas (SPNP) in children. The SPNP is heterogeneous and often
      shows evidence of a pseudocapsule and haemorrhage, reflecting the pathology of
      this tumour. In an appropriate clinical context an accurate preoperative
      diagnosis can be made without the need for biopsy. This is important because
      tumour seeding may be more important in chemoresistant tumours such as SPNP than
      in the more common paediatric neoplasms.

PMID- 15864575
TI  - Pituitary apoplexy.

PMID- 15864576
TI  - Whole-body MRI of paediatric malignant tumours: comparison with conventional
      oncological imaging methods.
AB  - PURPOSE: To evaluate the usefulness of whole-body (WB) MRI for detecting
      metastases from paediatric malignant tumours in comparison with conventional
      oncological imaging methods. MATERIALS AND METHODS: Using a 1.5-T system, a
      coronal short tau inversion recovery (STIR) sequence was obtained in all
      patients. In addition, sagittal fat-suppressed T2-weighted, sagittal STIR, or
      coronal fat-suppressed pre-contrast and post-contrast T1-weighted sequences were
      performed. Patients who underwent WB MRI and conventional oncological imaging
      within 15 days were enrolled in the study. In total, 58 bone scintigraphies, 26
      iodine-123 (123I) meta-iodo-benzylguanidine (MIBG) scintigraphies, and 48 CT
      scans were available for comparison in 36 patients (median age 3.5 years; 21
      boys, 15 girls) who underwent 82 WB MRI examinations. Skeletal and extraskeletal
      metastases were evaluated for a variety of tumour types. RESULTS: Concordance
      rate of WB MRI between two readers was 74%. In detecting metastases, WB MRI had
      higher sensitivity (99%) and PPV (94%) than bone scintigraphy (26 and 76%,
      respectively). In detecting skeletal metastases, WB MRI revealed higher
      sensitivity (100%) than 123I-MIBG scintigraphy (25%) and CT (10%). In contrast,
      WB MRI showed lower PPV in detecting skeletal and extraskeletal metastases (8 and
      57%, respectively) than 123I-MIBG scintigraphy (100%), and lower sensitivity
      (60%) in detecting extraskeletal metastases than CT (100%). In 2 of 11 untreated
      patients, tumour staging was upgraded from stage 3 to 4 according to WB MRI
      findings. In 3 patients, WB MRI revealed early treatment responses (<1 year) of
      skeletal metastases. CONCLUSIONS: WB MRI can substitute for bone scintigraphy in
      detecting skeletal metastases of paediatric malignant tumours, and it is useful
      in evaluating initial tumour staging and early treatment responses. However, it
      still has only a complementary role in detecting extraskeletal metastases.

PMID- 15864577
TI  - Non-gated fetal MRI of umbilical blood flow in an acardiac twin.
AB  - Currently, the standard method of diagnosis of twin reversed arterial perfusion
      (TRAP) sequence is ultrasound imaging. The use of MRI for flow visualization may
      be a useful adjunct to US imaging for assessing the presence of retrograde blood
      flow in the acardiac fetus and/or umbilical artery. The technical challenge in
      fetal MRI flow imaging, however, is that fetal electrocardiogram (ECG) monitoring
      required for flow imaging is currently unavailable in the MRI scanner. A non
      gated MRI flow imaging technique that requires no ECG monitoring was developed
      using the t-test to detect blood flow in 20 slices of phase-contrast MRI images
      randomly scanned at the same location over multiple cardiac cycles. A feasibility
      study was performed in a 24-week acardiac twin that showed no umbilical flow
      sonographically. Non-gated MRI flow images clearly indicated the presence of
      blood flow in the umbilical artery to the acardiac twin; however, there was no
      blood flow beyond the abdomen. This study leads us to conjecture that non-gated
      MRI flow imaging is sensitive in detecting low-range blood flow velocity and can
      be an adjunct to Doppler US imaging.

PMID- 15864578
TI  - Os odontoideum: a significant radiographic finding.
AB  - Os odontoideum can lead to instability of the atlantoaxial joint and places the
      spinal cord at significant risk for acute catastrophic events after minor trauma
      or chronic neurological change. We present two cases of os odontoideum in
      pediatric patients that were not appreciated at earlier remote imaging but were,
      in retrospect, detectable. One patient presented with an acute spinal cord
      injury. Incorporating assessment of dens integrity into the evaluation algorithm
      for all pediatric cervical spine studies should lead to early detection of os
      odontoideum lesions and allow referral to appropriate clinical spinal services
      for evaluation, surveillance and possible surgery to prevent future
      complications.

PMID- 15864579
TI  - Cerebral MRI findings in very-low-birth-weight and small-for-gestational-age
      children at 15 years of age.
AB  - BACKGROUND: A high prevalence of abnormal cerebral MRI findings has been reported
      in low-birth-weight children. OBJECTIVE: To compare MRI findings in very-low
      birth-weight (VLBW) and term small-for-gestational-age (SGA) children with
      controls in early adolescence. MATERIALS AND METHODS: Cerebral MRI was used to
      examine 55 VLBW, 54 SGA and 66 controls at 15 years of age. The MR images were
      qualitatively assessed, and size of ventricles, white-matter and grey-matter
      abnormalities were reported. RESULTS: The VLBW teenagers had a higher prevalence
      of various MRI abnormalities than SGA children and controls. Dilation of the
      ventricular system, especially of the occipital horns, was found in 82% of the
      VLBW group, in 19% of the SGA group and in 21% of controls. White-matter
      reduction was found in 53% of the VLBW, in 6% of the SGA and in 2% of controls.
      Corpus callosum thinning was found in 47% of the VLBW, in 2% of the SGA and in 6%
      of controls. Periventricular gliosis was found in 29% of the VLBW, in 4% of the
      SGA and in 8% of controls. CONCLUSIONS: Cerebral MRI pathology in white matter is
      a common finding in VLBW teenagers. The findings may indicate minor perinatal PVL
      with resulting loss of white-matter tissue and ventricular dilation.

PMID- 15864580
TI  - A versatile and general splitting technology for generating targeted YAC
      subclones.
AB  - Yeast artificial chromosomes (YAC) splitting technology was developed as a means
      to subclone any desired region of eukaryotic chromosomes from one YAC into new
      YACs. In the present study, the conventional YAC splitting technology was
      improved by incorporating PCR-mediated chromosome splitting technique and by
      adding autonomously replicating sequence (ARS) to the system. To demonstrate the
      performance of the improved method, a 60-kb region from within a 590-kb YAC
      (clone CIC9e2 from Arabidopsis thaliana chromosome 5) that could not be subcloned
      using the original method was split to convert into a replicating YAC. Two
      template plasmids, pSK-KCA and pSKCLY, were used to generate two splitting
      fragments by PCR. Two splitting fragments consisted of telomeric (C(4)A(2))(6)
      repeats, 400-bp target region, CEN4, H4ARS and Km(r) (selective marker for plant
      transformants), or CgLEU2. These splitting fragments were introduced into
      Saccharomyces cerevisiae harboring the 100-kb split YAC generated by splitting of
      the 590-kb YAC and containing the 60-kb region. Among 12 Leu(+) transformants,
      four exhibited the expected karyotype in which two newly split 40- and 60-kb
      chromosomes were generated. These results demonstrate that the improved method
      can convert a targeted region of a eukaryotic chromosome within a YAC into a
      replicating YAC.

PMID- 15864581
TI  - Molecular imaging of individual behaviour.

PMID- 15864582
TI  - Erdheim-Chester disease: 99mTc-MDP bone scan provides the diagnosis.

PMID- 15864583
TI  - Incremental prognostic value of dobutamine-atropine stress 99mTc-tetrofosmin
      myocardial perfusion imaging for predicting outcome in diabetic patients with
      limited exercise capacity.
AB  - PURPOSE: This study assessed the incremental value of dobutamine stress ( 99m)Tc
      tetrofosmin single-photon emission computed tomography (SPECT) for the prediction
      of cardiac events in diabetic patients with limited exercise capacity. METHODS:
      The study population comprised 125 consecutive diabetic patients (mean age 61+/-9
      years, 61% men) who were unable to perform an exercise test and underwent
      dobutamine ( 99m)Tc-tetrofosmin SPECT. Follow-up was successful in 124 (99%)
      patients. Three patients who underwent early revascularisation (within 60 days)
      were excluded. End-points during follow-up were cardiac death and non-fatal
      myocardial infarction. RESULTS: An abnormal scan (with the presence of reversible
      or fixed perfusion defects) was observed in 76 (63%) patients. During the follow
      up (3.4+/-1.5 years), 36 patients died (19 cardiac deaths) and four patients had
      non-fatal myocardial infarction. Cardiac death occurred in one of 49 (2%)
      patients with a normal myocardial perfusion study and in 18 of 75 (24%) patients
      with an abnormal study (p<0.001). Abnormal scan was incremental to the clinical
      parameters in predicting cardiac death (chi(2)=48 vs 39, p<0.05) and hard cardiac
      events (chi(2)=50 vs 43, p<0.05). CONCLUSION: Dobutamine stress ( 99m)Tc
      tetrofosmin SPECT provides prognostic information additional to clinical data for
      the prediction of cardiac death and hard cardiac events in diabetic patients
      unable to perform an exercise test.

PMID- 15864584
TI  - Improved pretargeted delivery of radiolabelled hapten to human tumour xenograft
      in mice by avidin chase of circulating bispecific antibody.
AB  - PURPOSE: Pretargeted therapy with radiolabelled bivalent haptens and bispecific
      antibodies has shown promising results, but blood clearance of the activity
      carrying haptens under conditions designed for radioimmunotherapy is relatively
      slow. Thus, the chase of excess circulating bispecific antibody by biotinylation
      of the bispecific antibody and injection of avidin before hapten administration
      was tested with a view to increasing tumour-to-blood activity ratios. METHODS:
      The anti-carcinoembryonic antigen (CEA) x anti-diethylene triamine penta-acetic
      acid-indium (di-DTPA-indium) bispecific antibody (hMN-14x734) was derivatised
      with NHS-LC-biotin and injected into LS-174T tumour-bearing nude mice at a dose
      of 3.5 nmol, followed by avidin and finally by the 125I-labelled di-DTPA-indium
      hapten (1 nmol). Blood samples were collected, animals sacrificed and tumours and
      normal tissues counted. RESULTS: Avidin chased up to 72% of the circulating
      antibody in the liver and the spleen within 30 min. When the labelled hapten was
      injected 3 h after avidin, tumour to blood ratios measured 3 and 24 h after
      hapten injection were significantly improved by the chase (3.5-fold), whereas
      tumour uptake was not significantly reduced. Uptake in normal tissues was
      unchanged (liver, kidney) or decreased (muscle), with the exception of spleen, in
      which uptake of both antibody and hapten was increased by the avidin chase.
      CONCLUSION: The chase strategy reduces hapten concentration in blood and thus
      should reduce bone marrow exposure. The use of two different recognition systems
      limits possible interference between the chase and targeting steps.

PMID- 15864585
TI  - Emerging evidence indicates that physiologically relevant thermal stress
      regulates dendritic cell function.
AB  - Elevations in temperature that are associated with inflammation or fever have
      been linked to improved survival from infections, enhanced immunological
      functions, and increased control of tumor growth. Over the past few years,
      several groups have begun to explore the possible linkage among these
      observations and have tested the hypothesis that various immune cells are
      especially sensitive to thermal stimulation. However, relatively little is known
      regarding the effects of thermal stimulation on antigen presenting cells (APCs),
      such as dendritic cells (DCs). Very recently, several groups have begun to
      examine the ability of thermal stimuli to regulate the function of these cells
      which are known to play a pivotal role in the efficacy of vaccines and other
      immunotherapies. In this review, we summarize what has been discovered about the
      role of mild thermal stress in regulating various Dendritic cell (DC) activities.
      Excitingly, it appears that mild elevations of temperature have the potential to
      enhance antigen uptake, activation associated migration, maturation, cytokine
      expression and T cell stimulatory activity of DCs. While these studies reveal
      that the timing, temperature and duration of heating is important, they also set
      the stage for essential questions that now need to be investigated regarding the
      molecular mechanisms by which elevated temperatures regulate DC function. With
      this information, we may soon be able to maximize the strategic use of thermal
      therapy as an adjuvant, i.e., combining its use with cancer immunotherapies such
      as vaccines, which depend upon the function of DCs. Several possible strategies
      and timepoints involving the clinical application of hyperthermia in combination
      with immunotherapy are presented.

PMID- 15864586
TI  - Increase in autoantibodies against Fas (CD95) during carcinogenesis in the human
      colon: a hope for the immunoprevention of cancer?
AB  - A thorough understanding of the naturally occurring events in the immune system
      in response to carcinogenesis will facilitate the development of strategies for
      the immunoprevention of cancer. The adenoma-carcinoma sequence in the human colon
      is a well-established clinical example of multi-step carcinogenesis and can be
      used for immunological studies. Based on previous observations that both
      apoptosis and the expression of Fas (Apo-1, CD95) are altered during
      carcinogenesis in the human colon, we asked the question whether serum titers of
      autoantibodies against Fas show any modification during the adenoma-carcinoma
      sequence. Healthy controls (38), patients with colorectal adenomas (38) and
      patients with colorectal adenocarcinomas (21) were investigated. Anti-Fas
      antibody titers were found to be significantly higher in patients with colorectal
      adenomas than in healthy controls and higher still in patients with colorectal
      adenocarcinomas. This increase in anti-Fas autoantibody titers during
      carcinogenesis might reflect the activation of natural defense mechanisms by the
      immune system.

PMID- 15864587
TI  - Combining proteasome inhibition with TNF-related apoptosis-inducing ligand
      (Apo2L/TRAIL) for cancer therapy.
AB  - Apoptosis has an essential role in embryogenesis, adult tissue homeostasis and
      cellular responses to stressful stimuli. Therefore, increased apoptosis is
      involved in the pathogenesis of various ischaemic, degenerative and immune
      disorders. Conversely, genetic aberration that results in a reduction or
      abolition of apoptosis can promote tumorigenesis and underlie the resistance of
      cancer cells to various genotoxic anticancer agents. Therefore, a detailed
      knowledge of the control of apoptotic pathways could aid in the rational design
      of effective therapeutics for a variety of human diseases including cancer. One
      major way to promote apoptosis involves signaling through members of the tumor
      necrosis factor (TNF) superfamily. On binding to their appropriate receptors,
      some TNF family members can promote caspase activation and apoptosis. Early
      studies on TNF indicated that a limited number of tumor cell lines could be
      induced to undergo apoptosis on exposure to TNF. Another member of the TNF family
      Fas ligand (FasL) is also known to induce apoptosis in a variety of tumor cells.
      Although TNF and FasL can efficiently induce apoptosis in a limited number of
      tumor cells, administration of either of these agents is associated with extreme
      toxicity. This toxicity has precluded further development of either TNF or FasL
      for cancer therapy. However, within the last 8 years another member of the TNF
      family, TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) has been
      characterized, which induces apoptosis of a wider range of cancer cells than
      either TNF or FasL. Surprisingly, most normal non-transformed cells are quite
      resistant to the apoptotic effects of Apo2L/TRAIL. This selective toxicity for
      cancer cells is the basis for the current enthusiasm for Apo2L/TRAIL as a
      potential novel anticancer therapy. In this symposium report, we provide a brief
      overview of Apo2L/TRAIL, its receptors and their signaling pathways. We discuss
      findings on the antitumor effects of Apo2L/TRAIL alone or in combination with
      radiotherapy or chemotherapy. In addition, we present recent information from our
      groups concerning the possible therapeutic benefits of combining Apo2L/TRAIL with
      the proteasome inhibitor bortezomib.

PMID- 15864588
TI  - Dendritic cell-based cancer immunotherapy targeting MUC-1.
AB  - Vaccination therapy using dendritic cells (DC) as antigen presenting cells (APC)
      has shown significant promise in laboratory and animal studies as a potential
      treatment for malignant diseases. Pulsing of autologous DCs with tumor-associated
      antigens (TAA) is a method often used for antigen delivery and choice of suitable
      antigens plays an important role in designing an effective vaccine. We identified
      two HLA-A2 binding novel 9-mer peptides of the TAA MUC1, which is overexpressed
      on various hematological and epithelial malignancies. Cytotoxic T cells generated
      after pulsing DC with these peptides were able to induce lysis of tumor cells
      expressing MUC1 in an antigen-specific and HLA-restricted fashion. Within two
      clinical studies, we demonstrated that vaccination of patients with advanced
      cancer using DCs pulsed with MUC1 derived peptides is well tolerated without
      serious side effects and can induce immunological responses. Of 20 patients with
      metastatic renal cell carcinoma, 6 patients showed regression of metastases with
      3 objective responses (1 CR, 2 PR). Furthermore, we found that in patients
      responding to treatment T cell responses for antigens not used for treatment
      occurred suggesting that antigen spreading in vivo might be a possible mechanism
      of mediating antitumor effects. These results demonstrate that immunotherapy in
      patients with advanced malignancies using autologous DCs pulsed with MUC1 derived
      peptides can induce immunological and clinical responses. However, further
      clinical studies are needed to identify the most potent treatment regimen that
      can consistently mediate an antitumor immune response in vivo.

PMID- 15864589
TI  - Immunostimulatory properties of human dendritic cells generated using IFN-beta
      associated either with IL-3 or GM-CSF.
AB  - Despite limited clinical efficacy in large trials, dendritic cells (DC)-based
      immunization has yielded impressive responses in some patients. Key questions
      remain to be solved in order to optimize this therapeutic vaccine. Among them,
      the nature of the DC type used and its state of maturation are pivotal. Besides
      myeloid DC which are mostly used in clinical trials, a new DC type has been
      recently described resulting from the differentiation of monocytes in the
      presence of type I IFNs. In the present study, we analyze the features of type I
      IFNs DC generated in the presence of either IL-3 (IL-3-DC) or GM-CSF (GM-CSF-DC)
      and compare their capacity to respond to poly(I:C) and to subsequently trigger T
      cell activation. The two DC types disclose a similar immunophenotype
      characterized by high levels of chemokines receptors, co-stimulatory and HLA
      molecules expression. After poly(I:C) maturation, both DC types display a marked
      upregulation of CD80, CD83 and CD86 and the same pattern of gene expression. In
      addition, poly(I:C) stimulated them to secrete IFN-alpha and IL-12p70. Both DC
      types elicit potent allogeneic reactions. Priming of autologous T cells by IL-3
      DC or GM-CSF-DC pulsed with an HLA-A2 restricted melan-A derived peptide, lead to
      the expansion of peptide specific CTL secreting high amounts of IFN-gamma. We
      conclude that poly(I:C) matured IL-3-DC and GM-CSF-DC share similar phenotype and
      functional properties including the capacity to prime tumor-associated antigen
      specific CTL.

PMID- 15864590
TI  - The role of MRSA screening in joint-replacement surgery.
AB  - The aim of this prospective study was to determine the effect of screening for
      methicillin-resistant Staphylococcus aureus (MRSA), in patients undergoing total
      hip and knee replacements, on reducing hospital-acquired infections and the
      length of hospital stay. We included 395 patients admitted to the elective
      orthopaedic ward for hip and knee replacements (knee 210; hip 185) from 16
      October 2000 to 15 October 2001. Group 1 included 164 admissions before 16 April
      2001 when MRSA swabs were not compulsory. Group 2 included 231 admissions after
      16 April 2001 when axillary, nasal and groin swabs had to be negative for MRSA.
      Four patients in group 1 had post-operative MRSA infection compared with none in
      group 2. The mean length of hospital stay decreased significantly from 10.43 days
      +/- SD 4.2 days in group 1 to 9.47 days +/- SD 2.6 days in group 2. There was a
      significant reduction in the incidence of hospital-acquired infections following
      the introduction of pre-admission screening.

PMID- 15864591
TI  - Efficacy of an intratumoral controlled release formulation of clusterin antisense
      oligonucleotide complexed with chitosan containing paclitaxel or docetaxel in
      prostate cancer xenograft models.
AB  - PURPOSE: To develop and evaluate an injectable, controlled release delivery
      system for a phosphorothioate antisense oligonucleotide (ASO) based on complexed
      ASO:chitosan dispersed in a biodegradable polymeric paste for intratumoral
      treatment of solid tumors. METHODS: Clusterin ASO was complexed with chitosan
      particles and incorporated into a paste based on a 60:40 blend of methoxy
      poly(ethylene glycol) (MePEG) and triblock copolymer of poly(D: ,L: -lactic acid
      co-caprolactone)-PEG-(D: ,L: -lactic acid-co-caprolactone). In vitro release
      profiles of clusterin ASO into phosphate-buffered saline at 37 degrees C were
      obtained under sink conditions and assayed by anionic exchange high-performance
      liquid chromatography. In vivo efficacy studies were carried out in human
      prostate PC-3 and LNCaP tumors grown subcutaneously in mice. Paste formulations
      of clusterin ASO with or without paclitaxel or docetaxel were injected
      intratumorally and tumor volumes and serum prostate specific antigen (PSA) levels
      were measured. RESULTS: Controlled release of clusterin ASO was obtained over
      several weeks. The rate and extent of ASO release was proportional to the ratio
      of ASO to chitosan in the paste. Treatment of mice bearing PC-3 tumors with
      clusterin ASO plus paclitaxel or docetaxel paste had reduced mean tumor volume by
      greater than 50% at 4 weeks. Treatment of mice bearing LNCaP tumors with
      clusterin ASO plus paclitaxel reduced mean tumor volume and serum PSA level by
      more than 50% and 70%, respectively. CONCLUSIONS: Complexation of clusterin ASO
      with chitosan and incorporation into polymeric paste with paclitaxel or docetaxel
      produced in vitro controlled release of the ASO and in vivo efficacy over 4 weeks
      following a single intratumoral injection in solid human prostate tumors in mice.

PMID- 15864592
TI  - Metabolism of docetaxel in mice.
AB  - Previous studies have shown by quantification of the parent drug and the known
      metabolites M-1, M-2, M-3 and M-4 that the mass balance of docetaxel in mice and
      humans is not complete. We therefore used reversed-phase high-performance liquid
      chromatography (HPLC) with photodiode array (PDA) detection and tandem mass
      spectrometry to trace and identify putative metabolites in the feces and bile of
      mice injected intravenously with docetaxel. HPLC-PDA revealed two metabolic
      products in the feces and more than ten potential new metabolites in the bile.
      Mass spectrometry was performed on docetaxel reference compound, on the known
      metabolites M-1, M-2, M-3 and M-4, and on HPLC eluate fractions containing
      metabolic products, six fractions originating from the bile and two from the
      feces. The mass spectra of the most abundant unknown metabolite in the bile and
      the feces were identical, and indicated that this structure contained a carboxyl
      moiety at the tert-butyl group. Under the conditions of storage this product
      degraded to metabolite M-4. All other unknown metabolites found in the bile
      samples were oxidized products, with the oxidations in both the C-13 side chain
      and the baccatin structure, the latter being a new finding.

PMID- 15864593
TI  - Diabetes insipidus presentation before renal and pulmonary features in a patient
      with Wegener's granulomatosis.
AB  - We report a case of a 47-year-old woman with Wegener's granulomatosis complicated
      by central diabetes insipidus. The patient had initially seronegative
      polyarthritis which mostly responded well to methotrexate and steroid therapy.
      Eight months later the patient suffered from polyuria and polydipsia. There were
      no abnormalities of the anterior pituitary hormones. MR images showed only loss
      of brightness of the posterior pituitary. Extensive evaluation of the patient
      revealed the presence of ANCA, in c-ANCA pattern and also PR3 positivity. Three
      months later findings of glomerulonephritis, as suggested by an active urine
      sediment and gradual proteinuria, and, finally, asymptomatic pulmonary nodules
      completed the clinical picture of Wegener's disease within 1 year. Renal biopsy
      showed crescent formation in two glomeruli, consistent with ANCA-related
      glomerulonephritis which showed pauci-immun depositions by direct
      immunofluorescence. Diabetes insipidus symptoms mostly regressed; renal and
      pulmonary findings completely disappeared with glucocorticoid and pulse
      cyclophosphamide treatment. These findings show that diabetes insipidus may
      rarely develop early in the disease process and ANCA positivity was directly
      indicative of Wegener's granulomatosis before the classic clinical signs of the
      disease.

PMID- 15864594
TI  - An efficient cryopreservation procedure for potato (Solanum tuberosum L.)
      utilizing the new ice blocking agent, Supercool X1000.
AB  - Cryopreservation has been recognized as a practical and efficient tool for long
      term storage of vegetatively propagated plants. This study was conducted to
      investigate effects of modified vitrification techniques on cryopreservation of
      potato. In vitro plants of potato cultivars "Superior" and "Atlantic" were cold
      acclimated, and axillary buds were precultured, osmoprotected, exposed to PVS-2
      solution, plunged into liquid nitrogen, thawed, and finally planted in the
      regeneration medium. In the modified vitrification technique an ice-blocking
      agent, Supercool X1000, was added with PVS-2 solution. Cold acclimation affected
      survival of cryopreserved shoot tips, and the highest survival (46.7%) was
      obtained after 3 weeks of acclimation at 10 degrees C. Shoot tips exposed to 2M
      glycerol plus 0.6M sucrose for 40 min gave 51.5% and 11.7% survival in "Atlantic"
      and "Superior" at 10 degrees C, respectively. Cold acclimated and osmoprotected
      shoot tips were dehydrated with PVS-2 containing different concentrations of
      Supercool X1000 prior to a plunge into liquid nitrogen. Treatments with 0.1% and
      1% of Supercool X1000 significantly improved survival by 55% in "Superior" and
      71.3% in "Atlantic", respectively. After cryopreservation, vitrified shoot tips
      resumed growth within a week in a medium (1 mg l(-1) GA(3), 0.5 mg l(-1) zeatin,
      and 0.1 mg l(-1) IAA) with a low level of Pluronic F-68 (0.005%) and survival was
      33.7% higher in "Atlantic" and 14.7% higher in "Superior" than the control
      (without Pluronic F-68).

PMID- 15864595
TI  - Intramedullary and extramedullary fat globules on magnetic resonance imaging as a
      diagnostic sign for osteomyelitis.
AB  - We retrospectively studied the frequency of persistent foci of fat signal on
      magnetic resonance (MR) imaging in osteomyelitis to assess its frequency, cause
      and diagnostic value. The radiographs and MR scans of 100 patients with a final
      diagnosis of osteomyelitis referred to a specialist orthopaedic oncology service
      with the presumptive diagnosis of a bone tumour were reviewed. The MR signal and
      morphological characteristics were recorded with particular attention to the
      presence of persistent fat signal within the infected area, which was classified
      as diffuse or focal. Seventeen cases were classified on radiographic grounds as
      acute, 63 as subacute and 20 as chronic osteomyelitis. In the acute group 12
      (70%) showed replacement of the marrow with fluid containing residual fatty
      signal, diffuse in seven and focal in five cases. Two cases showed predominantly
      fatty marrow with very early marrow oedema and three cases (18%) showed
      replacement of marrow fat with fluid and no residual fatty foci. None of the
      subacute group showed foci of fatty signal and two cases of inactive sclerosing
      osyeomyelitis in the chronic group showed restoration of normal marrow.
      Persistent fatty signal within the bone as well as soft tissues on MR imaging is
      a frequent finding in acute osteomyelitis. Radiological-pathological correlation
      suggests that the increasing intramedullary pressure leads to septic necrosis
      with death of the lipocytes and release of free fatty globules. This
      characteristic, but not pathognomonic, MR finding supports the diagnosis of
      osteomyelitis and may help to exclude the presence of a tumour.

PMID- 15864596
TI  - Effects of neck and circumoesophageal connective lesions on posture and
      locomotion in the cockroach.
AB  - Few studies in arthropods have documented to what extent local control centers in
      the thorax can support locomotion in absence of inputs from head ganglia.
      Posture, walking, and leg motor activity was examined in cockroaches with lesions
      of neck or circumoesophageal connectives. Early in recovery, cockroaches with
      neck lesions had hyper-extended postures and did not walk. After recovery,
      posture was less hyper-extended and animals initiated slow leg movements for
      multiple cycles. Neck lesioned individuals showed an increase in walking after
      injection of either octopamine or pilocarpine. The phase of leg movement between
      segments was reduced in neck lesioned cockroaches from that seen in intact
      animals, while phases in the same segment remained constant. Neither octopamine
      nor pilocarpine initiated changes in coordination between segments in neck
      lesioned individuals. Animals with lesions of the circumoesophageal connectives
      had postures similar to intact individuals but walked in a tripod gait for
      extended periods of time. Changes in activity of slow tibial extensor and coxal
      depressor motor neurons and concomitant changes in leg joint angles were present
      after the lesions. This suggests that thoracic circuits are sufficient to produce
      leg movements but coordinated walking with normal motor patterns requires
      descending input from head ganglia.

PMID- 15864597
TI  - Parasitoid wasp affects metabolism of cockroach host to favor food preservation
      for its offspring.
AB  - Unlike predators, which immediately consume their prey, parasitoid wasps
      incapacitate their prey to provide a food supply for their offspring. We have
      examined the effects of the venom of the parasitoid wasp Ampulex compressa on the
      metabolism of its cockroach prey. This wasp stings into the brain of the
      cockroach causing hypokinesia. We first established that larval development, from
      egg laying to pupation, lasts about 8 days. During this period, the metabolism of
      the stung cockroach slows down, as measured by a decrease in oxygen consumption.
      Similar decreases in oxygen consumption occurred after pharmacologically induced
      paralysis or after removing descending input from the head ganglia by severing
      the neck connectives. However, neither of these two groups of cockroaches
      survived more than six days, while 90% of stung cockroaches survived at least
      this long. In addition, cockroaches with severed neck connectives lost
      significantly more body mass, mainly due to dehydration. Hence, the sting of A.
      compressa not only renders the cockroach prey helplessly submissive, but also
      changes its metabolism to sustain more nutrients for the developing larva. This
      metabolic manipulation is subtler than the complete removal of descending input
      from the head ganglia, since it leaves some physiological processes, such as
      water retention, intact.

PMID- 15864598
TI  - The intermediate type split cord malformation: hypothesis and case report.
AB  - METHODS: A patient is described in which a complete osteofibrotic dorsally
      implanted septum was found in combination with a split cord malformation in a
      single dural tube. This case cannot be explained using the widely used theory as
      proposed by Pang et al. [Pang D, Dias MS, Ahab-Barmada M (1992) Split cord
      malformation, part I: A unified theory of embryogenesis for double spinal cord
      malformations. Neurosurgery 31:451-480] but must be regarded as a combination of
      type I and II split cord malformation. RESULTS: The authors state that all types
      of split cord malformation can be reduced to a single derailment during
      development, with various degrees of severity. CONCLUSIONS: The configuration of
      the malformation is determined by the way the median parts of the mesoderm come
      to development. Type I and II split cord malformation are not distinct entities.

PMID- 15864599
TI  - The role of endovascular treatment for pediatric aneurysms.
AB  - OBJECTIVES: To review all cases of pediatric aneurysms, we treated and evaluated
      their characteristics. The objective of the study is to compare between surgical
      and endovascular approaches regarding treatment and outcome. METHODS: All cases
      of pediatric intracranial aneurysms diagnosed and managed by our team in the last
      12 years were prospectively collected in our vascular malformation data base and
      reviewed. CONCLUSION: Pediatric aneurysms differ in their features when compared
      to adult aneurysms. Over the last years, there has been a gradual shift from
      traditional surgical approaches towards endovascular treatment of pediatric
      aneurysms. In our experience, patients treated by endovascular means had a better
      outcome than when treated by surgery. Whenever possible, endovascular treatment
      for pediatric aneurysms is the recommended approach. This offers both
      constructive and deconstructive techniques. Improved understanding with respect
      to the etiology of pediatric aneurysms will be the next step that will likely
      lead us to even better treatment decisions.

PMID- 15864600
TI  - Hydrocephalus in craniosynostosis: a review.
AB  - INTRODUCTION: Ventricular dilatation in the presence of primary craniosynostosis
      is a unique condition with respect to pathogenesis, clinical significance, and
      morphological appearance. It is rarely observed in nonsyndromic craniosynostosis,
      and in these cases usually attributable to coincidental disorders. Conversely, it
      is a common feature of syndromic craniosynostosis, affecting at least 40% of
      patients with Crouzon's, Pfeiffer's or the Apert syndrome. Shunt-dependent
      hydrocephalus is predominantly associated with Crouzon or Pfeiffer syndrome while
      in the Apert syndrome the usual finding is nonprogressive ventriculomegaly which,
      however, may also occur in some cases of Crouzon syndrome. PATHOGENESIS: The
      pathogenesis of progressive hydrocephalus remains somewhat obscure, a hypoplastic
      posterior fossa and a venous outlet occlusion at the skull base being the main
      causative factors discussed in literature. Ventriculomegaly may reflect primary
      brain maldevelopment or in some cases even a compensated state of increased
      cerebrospinal fluid (CSF) outflow resistance. CLINICAL EVALUATION: Clinical
      evaluation is mainly aimed at identifying progressive hydrocephalus, but
      diagnosis is hampered by the fact that classical clinical signs may be absent,
      and that ventricular dilatation will often become evident only after
      decompressive cranial surgery. Moreover, mild ventriculomegaly may in some cases
      coexist with intracranial hypertension from craniostenosis. Therefore, careful
      monitoring of intracranial pressure and ventricular size in the pre- and
      postoperative period is a diagnostic mainstay. CONCLUSION: In true hydrocephalus
      ventriculo-peritoneal shunting is currently the single promising mode of
      treatment.

PMID- 15864601
TI  - The effect of short-chain fatty acids butyrate, propionate, and acetate on
      urothelial cell kinetics in vitro: potential therapy in augmentation cystoplasty.
AB  - The intestinal element of enterocystoplasty is affected by chronic inflammatory
      changes, which lead to excess mucus production, urinary tract infections, and
      stone formation. There is also an increased risk of malignancy. These
      inflammatory changes may be due to diversion colitis, which affects colonic
      segments excluded from the faecal stream and likewise may respond to intraluminal
      short-chain fatty acid (SCFA) therapy. The SCFAs have interesting
      antiproliferative, differentiating, and pro-apoptotic effects, which are
      protective against colorectal cancer and may influence the risk of malignancy in
      enterocystoplasty. Before intravesical therapy can be considered, the effect on
      normal urothelium must be investigated. Primary urothelial cells cultured from
      biopsy specimens and transformed urothelial (RT112 and MGH-U1) and intestinal
      cell lines (HT29 and CaCo-2) were incubated with SCFAs. The 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to
      measure the residual viable biomass to assess cell proliferation. Proliferation
      of primary and transformed urothelial cells in culture was inhibited by all SCFAs
      in a similar time- and dose-dependent manner. The concentration of SCFA required
      to inhibit growth of primary cells by 50% (IC50) was 20 mM of butyrate, 120 mM of
      propionate, and 240 mM of acetate after incubation for 1 h. After 72 h the IC50
      was 2 mM of butyrate, 4 mM of propionate, and 20 mM of acetate. Transformed
      urothelial and colon cancer cell lines demonstrated similar growth inhibition.
      Butyrate was the most potent inhibitor of cell proliferation, followed by
      propionate and then acetate. Growth inhibition is not an immediate cytotoxic
      effect, and urothelial cells show a degree of adaptation to butyrate and growth
      recovery after incubation with butyrate. In conclusion, butyrate- and propionate
      induced growth inhibition is potentially clinically significant and may have
      therapeutically beneficial implications in vivo.

PMID- 15864602
TI  - Effect of the prostacyclin derivate iloprost in experimental caustic esophageal
      burn.
AB  - Previous experimental studies have suggested that administration of
      antithrombotic, antioxidant, and cytoprotective agents have protective effects in
      caustic injury of the esophagus. Therefore, an experimental study was carried out
      to investigate the effects of iloprost, a stable analogue of prostacyclin, on the
      esophagus after caustic burns. Sixty Wistar albino rats were divided into three
      groups of 20 animals each. In group A, animals were uninjured and untreated. In
      group B, animals were injured but untreated. In group C, rats were injured and
      administered intravenous iloprost for 3 days. Caustic esophageal burn was
      produced by 1 ml of 15% NaOH. Efficacy of the treatment was assessed by measuring
      the tissue malondialdehyde (MDA), superoxide dismutase, and glutathione levels
      with biochemical methods on the 3rd postoperative day. Histopathological
      evaluation was done on the 28th postoperative day. The level of MDA was
      significantly increased in group B compared with the other groups. In group B,
      the histopathological damage score was significantly higher than in groups A and
      C. There was also a significant difference between groups A and C regarding the
      histopathologic damage. These results indicate that iloprost has a preventive
      effect in experimental caustic esophageal burn in rats.

PMID- 15864603
TI  - HPV in anal squamous cell carcinoma and anal intraepithelial neoplasia (AIN).
      Impact of HPV analysis of anal lesions on diagnosis and prognosis.
AB  - BACKGROUND AND AIMS: Majority of cases of anal squamous cell carcinoma are human
      papilloma virus (HPV)-induced and result from anal intraepithelial neoplasia
      (AIN). This study was conducted to examine methods which may enable the routine
      diagnosis of HPV-induced changes in the anal rim and the consequences of such
      detection especially in view of a more sensitive diagnosis of AIN. Results were
      clinically correlated. METHODS: The study included biopsy samples from 87
      patients who had been diagnosed with the following disease patterns: 47 invasive
      anal carcinoma, 33 AIN of varying severity and seven condylomatous lesions. In 52
      of these cases, a tumour was clinically suspected. All biopsies were
      retrospectively examined for microscopic indications of HPV infection. After
      microdissection, additional HPV analysis via PCR was carried out. RESULTS: In 38
      of 47 cases of anal carcinoma, HPV DNA could be detected via PCR (80.9%), the
      majority of which were HPV 16 (33/38=86.8%). In 29 of the 33 cases of AIN, HPV
      DNA was detected (87.9%), most of these in AIN III (15/16=93.8%). Histological
      markers of HPV infection were detected in all 87 cases. DISCUSSION: In our
      series, the clinical diagnosis of the invasive anal carcinoma had a high
      sensitivity of 93.6%, with a specificity of 80%. The positive predictive value
      was 84.6%, and the negative predictive value 91.4%. In contrast, AIN had been
      detected clinically in none of the cases. In this situation, especially with high
      risk patients, our findings recommend anal HPV screening in combination with anal
      cytology and anoscopy. CONCLUSION: Based on our results, we urgently recommend
      for any histological report on excision of anal lesions to include a statement
      whether histological markers of HPV infection were detected. In individual cases,
      validation via HPV PCR must be considered.

PMID- 15864604
TI  - History of negative colorectal endoscopy and risk of rectosigmoid neoplasms at
      screening flexible sigmoidoscopy.
AB  - BACKGROUND AND AIMS: Screening sigmoidoscopy can reduce incidence of colorectal
      cancer and mortality. The optimal re-screening interval has not yet been defined.
      This study is aimed at estimating the risk of distal advanced adenomas (diameter
      >/=10 mm, villous component >20%, high-grade dysplasia) and cancer at screening
      flexible sigmoidoscopy in subjects aged 55-64 years who reported pre-screening
      negative colorectal endoscopy. PATIENTS: Eight thousands two hundred two subjects
      aged 55-64 years who underwent screening flexible sigmoidoscopy within the SCORE
      trial in Italy and who were able to report their previous history of colorectal
      endoscopy. RESULTS: Eight hundred eighty three of 8,202 subjects (10.8%) reported
      at least one prescreening negative endoscopy: among them, after 3-5 years, 6-10
      years and >10 years intervals between last reported examination and screening
      endoscopy, the Absolute Risk of advanced adenomas was 1.5%, 0.9% and 0.9%; one
      cancer was detected (0.1%). Among the 7,319 subjects who did not report
      prescreening endoscopy the risks of advanced adenoma and cancer were 3.2% and
      0.4%, respectively. Subjects with a previous colorectal examination had a 65%
      decreased risk of advanced adenomas (OR=0.35, 95%CI 0.18-0.66) and a 71%
      decreased risk of cancer (OR=0.29, 95%CI 0.04-1.12) as compared to those who did
      not. For subjects without family history of colorectal cancer the statistically
      significant decrease of the risk persisted up to ten years. The observed benefit
      seems not to apply to subjects with family history of colorectal cancer.
      CONCLUSIONS: Our results are consistent with the hypothesis that the interval
      between screening sigmoidoscopies could be safely expanded beyond 5 years for
      subjects without specific risk factors for colorectal cancer.

PMID- 15864605
TI  - Can pathological complete response in the primary tumour following pre-operative
      pelvic chemoradiotherapy for T3-T4 rectal cancer predict for sterilisation of
      pelvic lymph nodes, a low risk of local recurrence and the appropriateness of
      local excision?
AB  - INTRODUCTION: Local excision is considered inappropriate treatment for T3-T4
      rectal adenocarcinomas, as it cannot provide prognostic information regarding
      lymph node involvement and has a high risk of pelvic recurrence. Preoperative
      chemoradiation (CRT) studies in rectal cancer suggest that a pathological
      complete response (pCR) in the primary tumour provides an excellent long-term
      outcome. If downstaging to stage pT0 predicts a tumour response within the
      perirectal and pelvic lymph nodes, this may allow local excision to be performed
      without increased risk of pelvic recurrence. This retrospective study aimed to
      determine the incidence of involved lymph nodes following pCR (ypT0) after
      preoperative CRT and total mesorectal excision. METHOD: The outcome and treatment
      details of 211 patients undergoing preoperative CRT for clinically staged T3-T4
      unresectable rectal adenocarcinomas between 1993 and 2003 at Mount Vernon
      Hospital were reviewed. RESULTS: Data were recorded from the 143 patients who
      completed treatment with a median follow-up of 25 months. Twenty-three patients
      (18%) were found to have had a pCR. Four out of 23 patients (17%) had involved
      lymph nodes. No pelvic recurrences developed after a ypCR. Overall survival was
      similar for patients with ypT0 or residual tumour. CONCLUSION: Pathological
      complete response in the primary tumour failed to predict a response in the
      perirectal lymph nodes (p=0.08). The degree of response predicted a lymph node
      response (p=0.02). The detection of ypCR identified patients with a low rate of
      pelvic recurrence. This may in the future allow selection of patients for whom
      local excision can be performed without a higher risk of local relapse.

PMID- 15864606
TI  - Short- and-long term results of intraoperative radiofrequency ablation of liver
      metastases.
AB  - BACKGROUND: Surgical resection is the only therapeutic option with curative
      effect on malignant liver tumours, but in over 70% of cases, this is not a
      feasible option. A prospective study was performed to assess the short- and long
      term effects of intraoperative radiofrequency ablation on unresectable liver
      metastases. PATIENTS: Between 1997 and 2001, 57 patients (mean age 61.9 years;
      range 31-83 years) with 297 unresectable liver metastases (colorectal
      adenocarcinoma, n=38; carcinoid tumour, n=4; malignant melanoma, n=3; other
      metastases, n=12) underwent intraoperative radiofrequency ablation. RESULTS: No
      mortality was observed in patients managed solely with radiofrequency ablation.
      Eight postoperative complications occurred in eight patients (14%). Three
      occurred when radiofrequency ablation was combined with resection. Of the 33
      patients completely ablated, 30 patients are still alive and 21 are disease-free
      after a median follow-up of 18.1 months (range 2-43). Ten patients underwent more
      than one intraoperative radiofrequency ablation episode. Overall survival was
      72.5% at 1 year and 52.5% at 3 years. Complete ablation and the number of lesions
      were significant independent prognostic factors for survival, with p<0.001 and
      p<0.0001, respectively. CONCLUSION: Radiofrequency ablation is a safe and
      effective option for patients with inoperable liver metastases without extra
      hepatic disease. Prospective controlled trials comparing the results of different
      treatments are required to assess which patients will benefit best from this
      emerging new treatment.

PMID- 15864607
TI  - Effective antitumour mono- and combination therapy by gene delivery of
      angiostatin-like molecule and interleukin-12 in a murine hepatoma model.
AB  - METHODS: We applied an experimental approach employing two recombinant adenoviral
      vectors (Ad) that express interleukin-12 (IL-12) and angiostatin-like molecule
      (K1-3) respectively to a subcutaneous hepatoma model in mice. RESULTS: Injection
      of AdK1-3 into tumour nodules established by subcutaneous (s.c.) implantation of
      Hepa129 hepatoma cells in C3H mice resulted in a significant dose-dependent
      reduction in tumour growth by 57% in the high dosage group (5x10(9) plaque
      forming units [pfu], n=8) 10 days after treatment initiation. Similar
      antitumoural effects were found for the intratumoural mono-therapy with IL-12
      (2.5x10(9) pfu, n=8) resulting in 60% tumour inhibition at the same time point.
      The survival rate was significantly (p=0.009) improved in the IL-12 but not in
      the K1-3 treatment group. A combination therapy of AdK1-3 and AdIL-12 was also
      effective, but did not further improve antitumour efficacy compared with the
      monotherapy. CONCLUSION: In conclusion, both mono- and combination therapy of K1
      3 and IL-12 significantly inhibited tumour progression in this experimental
      tumour model. The co-administration of both compounds did not result in additive
      antitumour effects. We hypothesise that the lack of additive antitumour effects
      of the combination treatment might be attributed to partially counteracting
      antitumour effects and further studies are needed to illustrate the interference
      of tumour angiogenesis and tumour inflammation in this tumour model.

PMID- 15864608
TI  - Immune responses in advanced colorectal cancer following repeated intradermal
      vaccination with the anti-CEA murine monoclonal antibody, PR1A3: results of a
      phase I study.
AB  - BACKGROUND AND AIMS: The aim was to determine the toxicity, clinical and immune
      responses to the murine monoclonal anti-carcinoembryonic antigen (CEA) antibody,
      PR1A3, in patients with advanced colorectal cancer. MATERIALS AND METHODS:
      Fifteen patients with advanced colorectal cancer received either 0.5-, 1.0- or
      5.0-mg doses of PR1A3 mixed with 10% w/v Alum adjuvant (Superfos Biosector,
      Denmark) intradermally at 4-week intervals for 3 months. Patient serum was
      assessed for anti-idiotypic (Ab2), anti-anti-idiotypic (Ab3) and human anti-mouse
      antibody (HAMA) reactivity. Peripheral blood mononuclear cell (PBMC)
      proliferation with phytohaemagglutinin (PHA), CEA and PR1A3, stimulated IL-2, IL
      4 and IFN-gamma levels and PR1A3-stimulated IL-2 receptor expression during
      immunotherapy were determined. Comparisons were made with 16 age-matched controls
      without malignant disease. RESULTS: Hyperimmune sera from 12 of the 15 patients
      showed Ab2 reactivity with no detectable Ab3 responses. Strong HAMA reactivity
      was recorded in 7 of the 15 cases with no adverse clinical effect. Delayed-type
      hypersensitivity (DTH) responses developed in 12 of the 15 patients. Pre
      treatment PBMC proliferation with PHA was subnormal in each patient compared with
      controls, becoming normal (or supranormal) in all patients during immunisation
      (P<0.001). PBMC proliferation with CEA and PR1A3 increased during immunotherapy
      (P<0.001) along with stimulated production of IL-2, IFN-gamma and IL-2 receptor
      expression. Progressive disease was observed in 14 of the 15 patients with
      minimal toxicity. CONCLUSION: PR1A3 generated limited idiotypic responses but
      robust DTH reactivity in most patients. In vitro PBMC proliferation with mitogens
      and recall antigens is greatly increased during the course of immunisation, with
      a shift in stimulated cytokine profile.

PMID- 15864609
TI  - n-3, n-6, and n-9 polyunsaturated fatty acids--which composition in parenteral
      nutrition decreases severity of acute hemorrhagic necrotizing pancreatitis in
      rats?
AB  - BACKGROUND AND AIMS: Acute pancreatitis often requires parenteral nutrition.
      Thus, we analyzed, using a randomized trial, whether different fatty acids in
      parenteral nutrition influence lipidperoxidation and histopathology in acute
      pancreatitis in rats. MATERIALS AND METHODS: Seventy-five male Sprague-Dawley
      rats were randomized into five groups (gr.) (n=15). Gr. 1 underwent a laparotomy
      followed by saline infusion, gr. 2-5 received intraductal glycodeoxycholic acid
      (GDOC) followed by intravenous cerulein. Six hours after induction of
      pancreatitis (IOP), gr. 2 received saline infusion, while gr. 3 was infused with
      standard lipovenous (rich in [n-6] polyunsaturated fatty acids (PUFA)), gr. 4
      received ClinOleic (rich in [n-9] PUFA), while gr. 5 was infused with Omegaven
      (rich in [n-3] PUFA) for 18 h. After 24 h, all animals were sacrificed and the
      pancreas was determined histopathologically according to the severity of
      pancreatitis. Furthermore, pancreatic lipidperoxidation (TBARS) and activity of
      lipid production protective enzymes superoxide dismutase (SOD) and
      gluthationperoxidase (GSHPx) were analyzed. RESULTS: Omegaven infusion reduced
      the severity of histopathologic changes in acute pancreatitis and decreased
      lipidperoxidation (TBARS) in pancreatic tissue samples. Furthermore, pancreatic
      activity of SOD was increased. However, standard PUFA and ClinOleic infusion did
      not influence the severity of pancreatitis and lipidperoxidation. CONCLUSION:
      Parenteral nutrition high in n-3 PUFA seems to be superior to compositions of n-6
      or n-9 PUFA in the treatment of acute hemorrhagic pancreatitis in rats.

PMID- 15864610
TI  - Ileal pouch-anal anastomosis (IPAA): functional outcome after postoperative
      pelvic sepsis. A prospective study of 100 patients.
AB  - INTRODUCTION: The ileal pouch-anal anastomosis (IPAA) has become a standard
      procedure for patients with ulcerative colitis requiring surgical intervention.
      The technique has greatly improved and, since 1990, all patients at Huddinge
      University Hospital have been operated on with the double stapled technique.
      Pelvic sepsis is one of the most serious complications postoperatively, and,
      according to previous reports, leads to impaired function of the pouch and, in
      some cases, extirpation of the pouch. AIM: The purpose of this study was to find
      out if pelvic sepsis postoperatively after IPAA leads to impaired functional
      outcome at long-term follow-up. PATIENTS AND METHODS: One hundred consecutive
      patients with ulcerative colitis operated on between 1990 and 1997 with double
      stapled J-shaped pouches were followed prospectively with a standardised
      questionnaire, clinical follow-up and endoscopy of the pouch. The function of the
      pouch has been evaluated at a minimum of 2 years after surgery to compare the
      functional outcome between patients with and without pelvic sepsis
      postoperatively. RESULTS: Twelve patients developed pelvic sepsis
      postoperatively. No significant differences were found in pouch evacuation
      frequency, incontinence, deferral time, usage of protecting pads, skin
      irritation, evacuation problems, diet, usage of medication or social handicap.
      There was one failure in the control group. CONCLUSION: In this study, no
      evidence was found that suggested pelvic sepsis postoperatively impairs
      functional outcome after IPAA at long-term follow-up.

PMID- 15864611
TI  - D2-40, a novel monoclonal antibody against the M2A antigen as a marker to
      distinguish hemangioblastomas from renal cell carcinomas.
AB  - Hemangioblastomas (HB) are characterized by the presence of vacuolated tumor
      cells resembling the tumor cells seen in clear cell renal cell carcinomas (CRCC).
      The distinction between HB and metastatic CRCC in the brain is critical as they
      have different therapeutic and prognostic ramifications. The issue is further
      complicated by the possibility of both HB and metastatic CRCC in brains of
      patients with Von Hippel Lindau (VHL) disease. We studied the expression of a
      novel monoclonal antibody D2-40, which recognizes an oncofetal antigen (M2A) in
      HB and CRCC, by immunohistochemistry. The vacuolated tumor cells in all HB were
      stained positively with D2-40. Nineteen of 23 (83%) HB showed strong, membranous
      staining in the vacuolated tumor cells, and 4 of 23 (17%) showed weaker staining.
      No expression was seen in CRCC, either primary in the kidney (0/20), or
      metastatic CRCC in the brain (0/8). Three of the patients with HB also had VHL
      disease, and no difference was seen in D2-40 staining of HB in patients with or
      without VHL disease. Two of these three VHL disease patients had both primary
      CRCC and HB resected at our institution. In these two patients, strong D2-40
      expression was seen in the HB, but no expression was seen in the CRCC, underlying
      the utility of this marker in distinguishing HB from CRCC in patients with VHL
      disease in addition to sporadic cases. In summary, the monoclonal antibody D2-40
      is a useful marker to distinguish HB from CRCC.

PMID- 15864612
TI  - Peroxiredoxin I and II are up-regulated during differentiation of epidermal
      keratinocytes.
AB  - Peroxiredoxins (Prxs) are expressed in the epidermis, and the accentuated
      expression of the Prx I and Prx II isotypes (Prx I/II) in the suprabasal layers
      suggests the potential role of Prx I/II in epidermal differentiation. To evaluate
      the novel function of Prx I/II, we checked the modulation of Prx I/II in
      differentiating keratinocytes. To induce differentiation in vitro, normal human
      epidermal keratinocytes (NHEK) were cultured for up to 10 days after the
      confluent state (post-confluency). In Western blot analysis, the marked induction
      of Prx I was observed from the second day, but the marked induction of Prx II was
      observed later from the sixth day of post-confluency, when loricrin and
      transglutaminase 1 were induced (sixth day of post-confluency). When NHEK cells
      were treated with INF-gamma and TGF-beta1, Prx I/II were up-regulated by INF
      gamma, but Prx I/II were down-regulated by TGF-beta1. In summary, Prx I and Prx
      II are induced at the early and late stage of differentiation of NHEK cells,
      respectively.

PMID- 15864614
TI  - Bone cancer risk in mice exposed to 224Ra: protraction effects from promotion.
AB  - This paper analyzes data for the osteosarcoma incidence in life-time experiments
      of (224)Ra injected mice with respect to the importance of initiating and
      promoting action of ionizing high LET-radiation. This was done with the
      biologically motivated two step clonal expansion (TSCE) model of tumor induction.
      Experimentally derived osteosarcoma incidence in 1,194 mice following exposure to
      (224)Ra with different total radiation doses and different fractionation patterns
      were analyzed together with incidence data from 1,710 unirradiated control
      animals. Effects of radiation on the initiating event and on the clonal expansion
      rate, i.e. on promotion were found to be necessary to explain the observed
      patterns with this model. The data show a distinct inverse protraction effect at
      high doses, whereas at lower doses this effect becomes insignificant. Such a
      behavior is well reproduced in the proposed model: At dose rates above 6 mGy/day
      a longer exposure produces higher ERR per dose, while for lower rates the reverse
      is the case. The TSCE model permits the deduction of several kinetic parameters
      of a postulated two-step bone tumorigenesis process. Mean exposure rates of 0.13
      mGy/day are found to double the baseline initiation rate. At rates above 100
      mGy/day, the initiation rate decreases. The clonal expansion rate is doubled at 8
      mGy/day, and it levels out at rates beyond 100 mGy/day.

PMID- 15864615
TI  - Sudden unexpected death due to undiagnosed glioblastoma: report of three cases
      and review of the literature.
AB  - Although glioblastomas are among the most common primary cerebral neoplasms,
      sudden death due to these tumors is an uncommon event. Due to the usual rapid
      increase in intracranial pressure, patients develop symptoms rather early,
      leading to medical attention in time. A search for cases of sudden unexpected
      death due to undiagnosed glioblastoma from a total of 14,482 cases from the
      archives of the Institute of Legal Medicine in Hamburg in the period of 1991-2003
      revealed only one such case. Out of a total of 5,432 cases from the Institute of
      Neuropathology, Hamburg, during the same period, two further cases were found. A
      comprehensive literature review on cases of sudden death due to primary cerebral
      neoplasms published so far revealed a total of 83 cases with only ten cases of
      glioblastoma (12%), whereas 55 of these cases were due to histological benign
      tumors (66%).

PMID- 15864616
TI  - Polypoidal choroidal vasculopathy and photodynamic therapy with verteporfin.
AB  - BACKGROUND: We evaluated, in a nonrandomised, institutional, prospective study,
      the efficacy of photodynamic therapy (PDT) with verteporfin in age-related
      macular degeneration (AMD) eyes with polypoidal choroidal vasculopathy (PCV) and
      subfoveal exudation. METHODS: A prospective clinical and angiographic study was
      done in 40 consecutive eyes with PCV treated with PDT using masked best-corrected
      visual acuity (VA) and fluorescein and indocyanine green angiographic features at
      baseline and over 2 years. RESULTS: Twenty-one eyes completed 1-year follow-up
      and showed, after a mean 2.9 PDT sessions, VA improvement in 12 eyes, no change
      in five eyes, and VA decrease in four eyes. Leakage was absent at the retinal and
      choroidal level in 14 eyes at 1 year. Recurrence occurred in one eye during the
      first year. Six eyes completed 2 years of follow-up and showed, after a mean 4
      PDT sessions, VA improvement in five eyes and VA decrease in one eye. Leakage was
      absent at the retinal and choroidal level in five eyes. Recurrence occurred in
      four of these six eyes during the second year of follow-up. No serious adverse
      events were observed during the 2 years of follow-up. CONCLUSIONS: PDT with
      verteporfin was shown to be safe and effective for treating AMD eyes with PCV
      with subfoveal involvement. VA improvement and absence of leakage were achieved,
      respectively, in 57.1% and 66.6% of the eyes at 1 year. Recurrences were more
      frequent during the second year of follow-up.

PMID- 15864617
TI  - Associations between the deletion polymorphism of the angiotensin 1-converting
      enzyme gene and ocular signs of primary open-angle glaucoma.
AB  - BACKGROUND: Primary open-angle glaucoma (POAG) is a leading cause of blindness.
      High intraocular pressure (IOP) has been shown to be a key risk factor for POAG.
      Topical application of angiotensin 1-converting enzyme (ACE) inhibitors has been
      shown to lower IOP, and angiotensin-induced increase in vascular tone has been
      implicated as a pathogenetic mechanism in glaucomatous cupping and damage to the
      optic nerve. The objective of this study was to investigate the association
      between the deletion polymorphism in the ACE gene and ocular signs of POAG.
      METHODS: Baseline data from the Rotterdam Study was used. The ACE genotype was
      determined in 6,462 subjects. We used univariate and multiple variable
      statistical techniques to examine associations between ACE genotype and each of
      ocular hypertension, glaucomatous optic neuropathy, glaucomatous visual field
      defects and POAG diagnosis. RESULTS: We found no consistent evidence between ACE
      genotype and ocular signs of POAG. We did, however, find evidence of an
      association between ACE genotype and optic disc area, subjects homozygous for the
      deletion allele tending to have fractionally smaller optic disc areas than those
      with a single deletion allele subjects, who in turn tended to have fractionally
      smaller optic discs than those with no deletion alleles (P=0.01). CONCLUSIONS:
      The data provided little evidence of any association between ocular signs of POAG
      and the deletion polymorphism of ACE. There was, however, evidence that ACE may
      be associated with optic disc size-this was an unexpected finding.

PMID- 15864618
TI  - Changes in fundus autofluorescence in patients with age-related maculopathy.
      Correlation to visual function: a prospective study.
AB  - BACKGROUND: As members of the Fundus Autofluorescence in Age-related Macular
      Degeneration Study Group (FAM Study Group), we report changes of fundus
      autofluorescence (AF) in patients with multiple soft drusen in correlation to
      visual function. METHODS: Inclusion criteria were age >50 years, the presence of
      soft drusen, visual acuity of 20/100 or better, and no previous laser treatment
      in the study eye. All patients underwent a detailed ophthalmological examination
      including ETDRS visual acuity, binocular funduscopy, and color fundus
      photography. AF imaging was performed with a confocal scanning laser
      ophthalmoscope following a standard protocol. We used the classification of the
      International Fundus Autofluorescence Classification Group (IFAG) for the
      description of the AF patterns. RESULTS: One hundred and twenty-five patients (81
      women, 44 men) aged from 55 to 86 years (mean 70+/-7 years) were included in this
      prospective study. During follow-up (mean 18+/-6 months), 6 of 35 eyes with
      patchy AF pattern developed exudative changes, as well as 2 eyes with focal
      plaque-like AF pattern and 1 eye with reticular pattern at baseline. Geographic
      atrophy was seen in two eyes with focal AF pattern and one eye with focal-plaque
      like pattern at baseline. A total of 11 eyes presented with severe visual loss (>
      or = 6 ETDRS lines). Ten (91%) of these had patchy AF pattern. CONCLUSION:
      Imaging of fundus AF in patients with age-related maculopathy allows
      identification of different patterns of fundus AF. Our preliminary data suggest
      that a patchy pattern of AF indicates a relatively high risk of progression to
      age-related macular degeneration with visual loss.

PMID- 15864619
TI  - An assessment of the pattern of spontaneous eyeblink activity under the influence
      of topical ocular anaesthesia.
AB  - PURPOSE: To determine whether there is a change in the pattern of human eyeblink
      events under topical ocular anaesthesia. METHODS: Forty male subjects, aged
      between 19 and 52 years and with no significant ocular surface disease, were
      recruited. Their spontaneous eyeblink activity, in primary eye gaze position and
      in silence, was recorded for 5-min periods, before and after instillation of
      benoxinate 0.4% eyedrops. The surface anaesthesia was confirmed by
      aesthesiometry. RESULTS: The spontaneous eyeblink rate (SEBR) decreased from
      9.1+/-4.0 blinks/min to an average of 5.7+/-3.3 blinks/min, with 37 subjects
      showing a decreased eyeblink rate under anaesthesia. Three blink patterns were
      observed before anaesthesia (symmetrical, J-type and I-type) and these were
      essentially unchanged under anaesthesia. CONCLUSIONS: These studies confirm that
      the SEBR is usually reduced under surface anaesthesia (so is sensitive to
      exogenous control) but the pattern of the eyeblink activity is unchanged (so is
      less sensitive to exogenous control). The removal of exogenous stimuli by
      anaesthesia does not shift the eyeblink pattern to a single type, so indicates
      endogenous control.

PMID- 15864620
TI  - Transpalpebral measurement of intraocular pressure using the TGDc-01 tonometer
      versus standard Goldmann applanation tonometry.
AB  - BACKGROUND: A recently developed digital tonometer for transpalpebral intraocular
      pressure (IOP) measurement, distributed by Corneal, Inc., allows the noninvasive
      measurement of IOP for screening purposes. METHOD: We measured the IOP of 218
      eyes in 109 patients of the Interdisciplinary Uveitis Center of the University of
      Heidelberg with intact corneal epithelium. IOPs were measured first with the TGDc
      01 tonometer, and then by means of Goldmann tonometry. IOPs were recorded by two
      independent examiners. The mean of three measurements obtained with the TGDc-01
      was taken, whereas only one measurement was performed with the Goldmann
      tonometer. RESULTS: The mean difference between the TGDc-01 and Goldmann
      measurements was 3.7 mmHg. The standard deviation of the differences was +/-4.06
      mmHg. Thus measurements acquired with the TGDc-01 may range 4.4 mmHg above or
      11.8 mmHg below the values given by Goldmann tonometry. CONCLUSION: The IOP
      values obtained with the TGDc-01 were in poor agreement with Goldmann tonometry.
      We found a higher variation as well as a bias towards lower IOP values with the
      TGDc-01. It is a question of clinical judgement as to how far these deviating
      measurements can be accepted for screening purposes. Because the IOPs obtained
      with the TGDc-01 are generally lower and less accurate than those obtained with
      the Goldmann tonometer we believe that the TGDc-01 is not a reliable tool for IOP
      measurement in clinical routine.

PMID- 15864621
TI  - Cerebral hemodynamics in ocular hypertension.
AB  - PURPOSE: To evaluate the cerebral blood flow velocity in patients with ocular
      hypertension. MATERIAL AND METHODS: Twenty-four ocular hypertensive patients and
      24 age- and sex-matched healthy volunteers were recruited in a prospective
      comparative study. All subjects had normal findings on full-threshold visual
      field tests and clinically normal optic nerves. All patients with ocular
      hypertension had an intraocular pressure (IOP) of >21 mmHg on three separate
      occasions without treatment. Systolic and diastolic blood pressure by cuff, heart
      rate by palpation, IOP by Goldmann applanation tonometry, central corneal
      thickness by ultrasound pachymetry, blood flow velocities, and pulsatility index
      of the ipsilateral middle cerebral artery by transcranial color Doppler were
      measured. RESULTS: Systolic and diastolic blood pressures (P=0.40 and P=0.45,
      respectively), heart rate (P=0.30), and central corneal thickness (P=0.23) were
      similar in each group. Peak and end-diastolic blood flow velocities in the middle
      cerebral artery did not differ between ocular hypertensives and controls (P=0.37
      and P=0.87, respectively). In addition, pulsatility index did not significantly
      differ between ocular hypertensives and controls (P=0.61). CONCLUSIONS: The
      results of this study suggest that ocular hypertension is not associated with
      reduction in blood flow velocity and elevation of resistance in the middle
      cerebral artery.

PMID- 15864622
TI  - Correction of pre-existing astigmatism during cataract surgery: comparison
      between the effects of opposite clear corneal incisions and a single clear
      corneal incision.
AB  - BACKGROUND: Opposite clear corneal incisions (OCCIs) have been reported to reduce
      pre-existing astigmatism (PEA) during cataract surgery. Our goal was to evaluate
      the effect of OCCIs on correcting PEA in cataract surgery. METHODS: Non
      randomized prospective study. Thirty-four patients with PEA of greater than 1.5
      diopters (D) underwent clear cornea phacoemulsification cataract extraction with
      3.2-mm OCCIs (OCCI group). The control group consisted of 23 successive patients
      with PEA <1.5 D who underwent cataract extraction without OCCI. Best-corrected
      visual acuity, keratometry and refraction were recorded for all patients pre
      operatively and post-operatively. RESULTS: Using keratometric findings, mean
      astigmatism correction was 1.3 D (+/-0.9 SD; decreased from 2.6 D pre-operatively
      to 1.4 D post-operatively) in the OCCI group but only 0.4 D in the control group
      (P<0.005), 8 months post-operatively. Vector analysis of astigmatism correction
      showed greater change for OCCI patients (1.8 D vs 1.0 D, P=0.002). Using the
      Holladay method for calculating surgically induced refractive change (SIRC), the
      OCCI group showed a higher value of SIRC (-1.6 D vs -0.97 D), but this was not
      statistically significant. The OCCI patients showed a greater and significant
      change in refraction spherical equivalent than the controls. No complications
      related to OCCI or cataract surgery occurred during the follow-up period.
      CONCLUSIONS: Opposite clear cornea incision seems to be a simple, predictable,
      safe and effective procedure in reducing pre-existing corneal astigmatism in
      cataract surgery. It has an enhanced effect in correcting astigmatism compared to
      a single clear cornea incision when using keratometric findings value but not
      when using refractive data. Future studies are needed to document the long-term
      effect of OCCI and to evaluate the correlation between incisions of different
      size and astigmatism correction.

PMID- 15864623
TI  - May glutathione S-transferase M1 positive genotype afford protection against
      primary open-angle glaucoma?
AB  - PURPOSE: To find out whether the polymorphism at GSTM1, GSTT1 and GSTP1 loci is
      associated with increased susceptibility to glaucoma. METHODS: We genotyped 153
      primary open angle patients and 159 healthy controls. Genomic DNA from peripheral
      blood was examined using polymerase chain reaction and defined for the genetic
      polymorphisms of glutathione S-transferase. RESULTS: The frequency of the GSTM1
      null genotype individuals among the glaucoma patients was significanlty higher
      than in controls (54.9 vs 40.9%) with odds ratio of 1.64 (95% CI: 1.10-2.59). The
      frequency of the GSTT1 and GSTP1 in both groups were not statistically different.
      CONCLUSION: The present study suggests that the GSTM1 null genotype may be a
      genetic risk factor for development of primary open angle glaucoma. Further
      associations studies in other polymorphic genes for xenobiotic-metabolizing
      enzymes are needed to elucidate the environmental-genetic interaction in the
      underlying cause of primary open angle glaucoma.

PMID- 15864624
TI  - Influence on membrane-mediated cell activation by vesicles of silicone oil or
      perfluorohexyloctane.
AB  - PURPOSE: This study was conducted to investigate whether macrophage activation
      through cell membrane attachment might be supported by emulsified tamponade
      droplets of a certain vesicle size. It has been hypothesized that emulsification
      of vitreous tamponades might stimulate retinal membrane formation. METHODS: In
      this laboratory investigation, similarly sized vesicles of silicone oil and the
      partially fluorinated alkane perfluorohexyloctane (F6H8) were produced by
      extrusion through polycarbonate membranes. Human neutrophils were obtained from
      blood donors. Human monocytes were negatively isolated from mononuclear cells by
      depletion of other cells. Cell activation status of phagocyting blood neutrophils
      was measured by a chemiluminescence assay. Fluorescent attached or internalized
      vesicles were monitored by fluorescent microscopy. The main outcome measures were
      the altered activation status of monocytes after vesicle incubation and the
      ability of human macrophages to attach and/or internalize vesicles in vitro.
      RESULTS: Extruding silicone oil through a polycarbonate membrane resulted in the
      production of vesicles that remained stable for at least 2 days. F6H8 vesicles
      had to be stabilized with an emulsifier, in this case Pluronic PE6800 or Lipoid
      EPC. The mean vesicle diameter was similar with both components (F6H8: 13.08+/
      2.95 microm, silicone oil: 10.05+/-4.6 microm). Neutrophil activation was not
      influenced by either emulsifier alone or by silicone oil vesicles without
      emulsifier. Stabilized F6H8 vesicles had a dose-dependent influence on blood
      neutrophil activation. Only silicone oil vesicles together with Lipoid EPC, not
      Pluronic PE6800, had a comparable influence on neutrophil activation. Neutrophil
      activation was influenced neither by 0.125% human serum albumin (HSA) alone nor
      by vesicles of F6H8 or silicone oil prepared with 0.125% HSA. Monocyte cell
      membrane attachment of silicone fluid was two times higher than that of F6H8
      fluid. F6H8/Pluronic PE6800 vesicles enhanced this process 20-fold, whereas
      silicone oil vesicles did not enhance cell membrane attachment significantly.
      CONCLUSIONS: These in vitro data do not support the hypothesis that
      emulsification of the tamponades silicone oil or F6H8 in the microenvironment of
      the eye might easily activate neutrophils or stimulate phagocytosis by monocytes.
      A prerequisite is the combination of a vesicle shape of the tamponades with
      specific stabilizing or modifying surfactants. Emulsified tamponades stabilized
      by artificial surfactants, but not by the naturally occurring protein HSA, favor
      cell activation by cell membrane attachment.

PMID- 15864625
TI  - Accuracy of dynamic contour tonometry compared with applanation tonometry in
      human cadaver eyes of different hydration states.
AB  - BACKGROUND: In an experimental laboratory investigation we compared intraocular
      pressure (IOP) measurements obtained by dynamic contour tonometry (DCT), Goldmann
      applanation tonometry (GAT), and pneumatonometry (PTG) with intracameral
      manometry on human cadaver corneas of different hydration conditions. METHODS:
      Ten freshly enucleated eyes were de-epithelialized. Two tubes were placed in the
      anterior chamber in opposite directions and connected to a transducer and to a
      bottle system filled with balanced salt solution. The pressure in the eye was
      then adjusted between 5 mmHg and 58 mmHg by electronically altering the height of
      the bottle. Central corneal thickness (CCT) was registered and IOP measurements
      were obtained with DCT, GAT, and PTG at each manometric pressure reading.
      Immediately after the trial the same corneas were artificially dehydrated and the
      same measurement regimen was repeated. RESULTS: In the pressure range defined by
      the bottle height 10-50 cm, IOP values measured by DCT were 0.50 mmHg (95%
      CI=0.40-0.60) and 0.36 mmHg (95% CI=0.25-0.47) higher than manometric readings
      before and after dehydration, respectively. GAT showed consistently lower values
      than manometry, the difference being -3.48 mmHg (95% CI=-3.91 to -3.05) and -3.14
      mmHg (95% CI=-3.39 to -2.89), respectively. Similar results were obtained with
      PGT, namely differences of -4.75 mmHg (95% CI=-5.21 to -4.29) and -3.98 mmHg (95%
      CI=-4.48 to -3.48) for the hydrated and the dehydrated corneal condition,
      respectively. Only DCT showed no significant change in accuracy between hydrated
      and dehydrated corneas. CONCLUSIONS: In this in vitro study DCT values for IOP
      were significantly closer to the manometric reference pressure than those
      obtained using GAT and PTG, independent of the state of corneal hydration.

PMID- 15864626
TI  - A patient with sarcoidosis diagnosed by a biopsy of scleral nodules.
AB  - PURPOSE: To report the case of a patient with nodular scleritis who was diagnosed
      as having sarcoidosis by a biopsy of scleral nodules. METHODS: Case report.
      RESULTS: A 26-year-old man with nodular scleritis underwent a biopsy of scleral
      nodules. The year before, he had been diagnosed with granulomatous iridocyclitis
      of the right eye. Although sarcoidosis had been suspected, extensive systemic
      examinations resulted in no positive findings of sarcoidosis. Histopathological
      specimens revealed non-caseating epithelioid granuloma with giant cells. The
      nodular scleritis was resolved by topical corticosteroids. CONCLUSIONS: A scleral
      biopsy is useful for the diagnosis of sarcoidosis when the patient has nodular
      scleritis with no systemic signs.

PMID- 15864627
TI  - Scleral and corneal laceration with iris prolapse caused by an eagle claw.
AB  - BACKGROUND: To describe the visual rehabilitation after surgical treatment of an
      ocular injury sustained during an attack by a bird of prey. METHODS: A 51-year
      old woman who was attacked by an eagle in a cage had a laceration of cornea and
      sclera at 9 o' clock, an iris prolapse that was jammed into the scleral wound,
      and a flat anterior chamber with hyphema. The uncorrected visual acuity was hand
      movements. Surgical treatment was performed immediately and included iris
      repositioning and suturing, scleral and conjunctival suturing, and transscleral
      cryotherapy to the retina. RESULTS: Eight months later, the best corrected visual
      acuity was 20/20. The anterior segment showed a posterior synechia in the area of
      the iris repair and an almost round pupil; the crystalline lens showed only a
      localized opacification. CONCLUSIONS: A bird of prey, even though caged, can
      injure an eye in humans. With immediate surgical treatment, good visual
      rehabilitation was achieved in this case. It should be reiterated that spectacles
      offer no protection against ocular trauma in these cases.

PMID- 15864628
TI  - Diagnostic value of mitochondrial DNA mutation analysis in juvenile unilateral
      ptosis.
AB  - PURPOSE: To highlight the diagnostic relevance of mitochondrial DNA (mtDNA)
      mutation analysis in acquired juvenile unilateral upper eyelid ptosis. METHODS: A
      13-year-old boy presented with acquired, slowly progressive unilateral ptosis. We
      performed ophthalmological and neurological examinations, laboratory testing,
      skeletal muscle biopsy including histological and histochemical investigations,
      biochemical analysis of respiratory chain enzymes in skeletal muscle homogenate
      and molecular genetic testing of skeletal muscle DNA. RESULTS: Though clinical,
      laboratory, histological and biochemical analyses did not reveal any hints
      suggesting a mitochondrial cytopathy, molecular genetic testing by Southern blot
      analysis of total DNA from skeletal muscle tissue showed a 5.8 kb mtDNA deletion
      thus proving the diagnosis of mitochondrial chronic progressive external
      ophthalmoplegia (CPEO). CONCLUSIONS: In patients with unexplained acquired
      juvenile unilateral ptosis, an underlying mitochondrial cytopathy should be
      considered even in cases of inconspicuous ancillary examinations comprising
      skeletal muscle histology and biochemistry. To establish the diagnosis, molecular
      genetic testing of DNA derived from skeletal muscle tissue is essential in those
      patients.

PMID- 15864629
TI  - Von Willebrand's disease type I as a cause for subvitreal, retinal and subretinal
      haemorrhages.
AB  - BACKGROUND: Young patients with vitreous, retinal and subvitreal haemorrhages
      without neovascularisation or prior trauma are a diagnostic challenge for the
      physician. In this case report, a patient is presented who developed unilateral,
      spontaneous, subvitreal, retinal and subretinal haemorrhages and was diagnosed
      with von Willebrand's disease. CASE REPORT: A 33-year-old Caucasian woman
      presented at our clinic with unilateral subvitreal, retinal and subretinal
      haemorrhages. The haemorrhages occurred spontaneously without prior trauma, and
      the patient had no history of prior bleeding complications. Analysis of the
      coagulation-fibrinolysis system and von Willebrand multimer analysis led to the
      diagnosis von Willebrand's disease type I. CONCLUSIONS: Spontaneous subvitreal,
      retinal and subretinal haemorrhages may be associated with coagulation disorders.
      Especially in young patients, von Willebrand's disease should be considered as a
      possible cause.

PMID- 15864630
TI  - Hypopyon uveitis associated with systemic lupus erythematosus and
      antiphospholipid antibody syndrome.
AB  - PURPOSE: To report a case of hypopyon uveitis associated with systemic lupus
      erythematosus and antiphospholipid antibody syndrome. METHODS: Interventional
      case report: a 49-year-old woman with a history of systemic lupus erythematosus
      and antiphospholipid antibody syndrome presented with sudden onset of pain,
      redness, photophobia, and decreased vision in the left eye. Examination revealed
      hypopyon uveitis and vaso-occlusive retinopathy. RESULTS: Following treatment
      with intravenous steroids and cyclophosphamide, the patient's vision improved
      from CF to 20/80 with no inflammation 6 months following initial presentation.
      CONCLUSIONS: In this case, systemic lupus and antiphospholipid syndrome were
      associated with hypopyon uveitis. Prompt treatment with systemic
      immunosuppressive therapy resulted in improvement in the hypopyon uveitis and
      vaso-occlusive retinopathy.

PMID- 15864631
TI  - Current external and internal exposure to naphthalene of workers occupationally
      exposed to polycyclic aromatic hydrocarbons in different industries.
AB  - OBJECTIVES: External and internal exposure to naphthalene was examined in the
      most important industries that are typically concerned with polycyclic aromatic
      hydrocarbon (PAH)-induced diseases (cancer). Furthermore, a control collective
      from the general population was investigated. METHODS: External naphthalene was
      determined by personal air sampling (n = 205). The internal exposure was examined
      by urinary metabolites 1-naphthol and 2-naphthol (n = 277). RESULTS: Highest
      median concentrations of naphthalene in air were found in converter infeed (93.2
      microg/m3) and coal-tar distillation (35.8 microg/m3). Moderate and low levels
      were determined in coking plants (14.5 microg/m3) and in the production of
      refractories (6.1 microg/m3) and graphite electrodes (0.7 microg/m3). Biological
      monitoring revealed concentrations of the sum of both metabolites [(1+2)-NOL] in
      smokers to be increased by 1.6-6.4 times compared with that in non-smokers at the
      same workplaces. Among non-smokers we found high median (1+2)-NOL levels in
      converter bricklayers (120.1 microg/l), in coal-tar distillation workers (56.0
      microg/l) and in coking plant workers (29.5 microg/l). (1+2)-NOL concentrations
      around 10 microg/l were found in the production of refractories and graphite
      electrodes. There was a rough coherency between external and internal naphthalene
      exposure. In the controls, median (1+2)-NOL concentrations were 10.9 microg/l in
      non-smokers' urine and 40.3 microg/l in smokers' urine samples. CONCLUSIONS:
      Actual conditions of occupational hygiene at the workplaces investigated in this
      comprehensive study are better than those that current limit values of 50,000
      microg/m3 (TLV, TRK) seem to induce. It has become obvious that tobacco smoking
      is a crucial confounding factor in biological monitoring of naphthalene-exposed
      humans, making interpretation of occupationally increased naphthol excretions
      very difficult at low exposure levels.

PMID- 15864632
TI  - Urinary sevoflurane and hexafluoro-isopropanol as biomarkers of low-level
      occupational exposure to sevoflurane.
AB  - OBJECTIVES: Sevoflurane is an inhalation halogenated anaesthetic widely used in
      day and paediatric surgery. We were interested in evaluating biological markers
      of exposure to sevoflurane, which should improve the health surveillance of
      occupationally exposed personnel. METHODS: A group of 36 subjects (13 male, 23
      female) occupationally exposed to volatile anaesthetics in paediatric operating
      rooms was studied in a 2-week survey. Post-shift urine samples and specimens from
      passive samplers (for personal monitoring) were collected after 1.75-6 h morning
      exposure and analysed by headspace gas chromatography-mass spectrometry (GC-MS).
      Multiple determinations were assumed as independent values (in total, n = 78: 24
      from men, 54 from women; 25 from smokers, 53 from non-smokers). RESULTS: Median
      sevoflurane external values were 0.13 parts per million (ppm) (range 0.03-18.82)
      (n = 78), urinary sevoflurane 0.6 microg/l urine (ND-18.5)(n = 76) and total
      urinary hexafluoro-isopropanol (HFIP) 0.49 mg/l urine (ND-6833.4) (n = 75). A
      lower limit of detection (LOD) was achieved for urinary sevoflurane (0.03
      microg/l urine), allowing quantitation of all but one of the samples; >25% of
      urine samples were unquantifiable by HFIP and were assigned a value equal to half
      the LOD of 0.10 mg/l(urine). Urinary sevoflurane correlated well with breathing
      zone data (r2 = 0.697 at log-log linear regression), whereas total urinary HFIP
      (r2 = 0.562 at log-log linear regression) seemed to be better described by a
      three-parameter logistic function and appeared to be influenced by smoking
      habits. Biological indices corresponding to National Institute for Occupational
      Safety and Health (NIOSH) exposure limits, calculated as means of linear
      regression slope and y intercept, were 3.9 mug/l(urine) and 1.4 microg/l urine
      for sevoflurane (corresponding to 2 ppm and 0.5 ppm, respectively), and 2.66 mg/l
      urine and 0.82 mg/l urine for HFIP. CONCLUSIONS: On the basis of our data,
      urinary unmodified, sevoflurane seems to be a more sensitive and reliable
      biomarker of short-term exposure to sevoflurane with respect to total urinary
      metabolite HFIP, which appears to be influenced by physiological and/or genetic
      individual traits, and seems to provide an estimate of integrated exposure.

PMID- 15864633
TI  - Ulnar and tibial bending stiffness as an index of bone strength in synchronized
      swimmers and gymnasts.
AB  - The purpose of this study is to compare a mechanical property of bone in world
      class female athletes with different loading histories. Bone bending stiffness or
      EI (E is the modulus of elasticity and I, the moment of inertia) was measured
      noninvasively with the mechanical response tissue analyzer, that analyzes the
      response of bone to a vibratory stimulus. We evaluated the ulna, ulnar width,
      wrist density and tibia in 13 synchronized swimmers (SYN), eight gymnasts (GYM)
      and 16 untrained women (UNT) of similar age. Muscle strength in the flexors and
      extensors at elbows and knees was measured in the athletes. SYN were taller than
      GYM or UNT (168 +/- 0.7 vs. 152 +/- 1.1 or 157 +/- 1.2 cm, P < 0.01). Ulnar EI,
      Nm(2), was similar in SYN and GYM (41 +/- 5.4 vs. 42 +/- 4.2, NS) and 50% higher
      than in UNT (27 +/- 2.1, P < 0.05). Ulnar EI, Nm(2) was related to ulnar width (r
      = 0.497, P < 0.002, n = 37) but not to wrist density. Tibial EI, Nm(2), in SYN
      and GYM (270 +/- 42 vs. 285 +/- 49, NS) was similar and more than twice as high
      as in UNT (119 +/- 6; p < 0.05). Knee flexor strength measured at 60 degrees s(
      1) and elbow extensor strength at 200 degrees s(-1) correlated with tibial EI (r
      = 0.44 and 0.41, P < 0.05). In spite of different loading histories, the tibiae
      and ulnas of world-class athletes showed similar high values for bending
      stiffness that exceeded values in untrained women. EI in the ulna could be
      related to bone width and in the tibia, to muscle strength.

PMID- 15864634
TI  - Effects of inspiratory impedance on hemodynamic responses to a squat-stand test
      in human volunteers: implications for treatment of orthostatic hypotension.
AB  - Recent studies in our laboratory demonstrated that spontaneous breathing through
      an inspiratory impedance threshold device (ITD) increased heart rate (HR), stroke
      volume (SV), cardiac output (Q), and mean arterial blood pressure (MAP) in supine
      human subjects. In this study, we tested the effectiveness of an ITD as a
      countermeasure against development of orthostatic hypotension, provoked using a
      squat-to-stand test (SST). Using a prospective, randomized blinded protocol, 18
      healthy, normotensive volunteers (9 males, 9 females) completed two
      counterbalanced 6-min SST protocols with and without (sham) an ITD set to open at
      0.7 kPa (7-cm H(2)O) pressure. HR, SV, Q, total peripheral resistance (TPR), and
      MAP were assessed noninvasively with infrared finger photoplethysmography.
      Symptoms were recorded on a 5-point scale (1 = normal; 5 = faint) of subject
      perceived rating (SPR). The reduction in TPR produced by SST (-35 +/- 5 %) was
      not affected by the ITD. Reduction in MAP with ITD during the transient phase of
      the SST (-3.6 +/- 0.5 kPa or -27 +/- 4 mmHg) was less (P = 0.03) than that
      measured while breathing through a sham device (-4.8 +/- 0.4 kPa or -36 +/- 3
      mmHg) despite similar (P < 0.926) elevations in HR of 15 +/- 2 bpm. SV (+2 +/- 4
      %) and Q (+22 +/- 5 %) with the ITD were higher (P < 0.04) than SV (-8 +/- 4 %)
      and Q (+10 +/- 6 %) without the ITD. SPR was 1.4 +/- 0.1 with ITD compared to 2.0
      +/- 0.2 with the sham device (P < 0.04). This reduction in orthostatic symptoms
      with application of an ITD during the SST was associated with higher MAP, SV and
      Q. Our results demonstrate the potential application of an ITD as a
      countermeasure against orthostatic hypotension.

PMID- 15864635
TI  - Confounding factors in the use of the zero-heat-flow method for non-invasive
      muscle temperature measurement.
AB  - This study evaluated a zero-heat-flow (ZHF), non-invasive temperature probe for
      in- vivo measurement of resting muscle temperature for up to 2 cm below the skin
      surface. The ZHF probe works by preventing heat loss from the tissue below the
      probe by actively heating the tissue until no temperature gradient exists across
      the probe. The skin temperature under the probe is then used as an indicator of
      the muscle temperature below. Eight subjects sat for 130 min during exposure to
      28 degrees C air. Vastus lateralis (lateral thigh) muscle temperature was
      measured non-invasively using a ZHF probe which covered an invasive multicouple
      probe (which measured tissue temperature 0.5 cm, 1 cm, 1.5 cm, and 2 cm below the
      skin) located 15 cm superior to the patella (T (covered)). T (covered) was
      evaluated against an uncovered control multicouple probe located 20 cm superior
      to the patella (T (uncovered)). Rectal temperature and lateral thigh skin
      temperature were also measured. Mean T (uncovered) (based on average temperatures
      at the 0.5 cm, 1 cm, 1.5 cm, and 2 cm depths) and Mean T (covered) were similar
      from time 0 min to 60 min. However, when the ZHF was turned on at 70 min, Mean T
      (covered) increased by 2.11 +/- 0.20 degrees C by 130 min, while T (uncovered)
      remained stable. The ZHF probe temperature was similar to T (covered) at 1 cm and
      after time 85 min, significantly higher than T (covered) at the 0.5 cm, 1.5 cm,
      and 2 cm depths; however from a physiological standpoint, the temperatures
      between the different depths and the ZHF probe could be considered uniform (< or
      =0.2 degrees C separation). Rectal and thigh skin temperatures were stable at
      36.99 +/- 0.08 degrees C and 32.82 +/- 0.23 degrees C, respectively. In
      conclusion, the non-invasive ZHF probe temperature was similar to the T (covered)
      temperatures directly measured up to 2 cm beneath the surface of the thigh, but
      all T (covered) temperatures were not representative of the true muscle
      temperature up to 2 cm below the skin because the ZHF probe heated the muscle by
      2.11 +/- 0.20 degrees C during its operation.

PMID- 15864636
TI  - Effects of physical training on heat loss responses of young women to passive
      heating in relation to menstrual cycle.
AB  - To examine the effects of physical training on cutaneous vasodilation and
      sweating responses of young women in the follicular and luteal phase, 11
      physically trained (T group) and 13 untrained (U group) women were passively
      heated by lower-leg immersion into hot water of 42 degrees C (ambient temperature
      of 30 degrees C and 45%RH) for 60 min in their mid-follicular and mid-luteal
      phases of the menstrual cycle. Female hormones increased significantly from the
      mid-follicular to the mid-luteal phase in T and U groups, but the degree of
      increase was significantly lower in T group. Mean body temperature (T(B))
      thresholds for cutaneous vasodilation and sweating responses were significantly
      lower in T group than in U group, in both the menstrual phases, and the
      differences between the groups were greatest during the mid-luteal phase. The
      slope of the relationship between frequency of sweat expulsion (F(sw)) and
      (T(B)), and between local sweating rate and F(sw) was significantly greater in T
      group, although the slope of the relationship between cutaneous blood flow and
      (T(B)) did not differ between the groups, regardless of body site or menstrual
      phase. These results suggest that regular physical activity enhanced sweating and
      cutaneous vasodilation in young women. The enhancement of sweating was due to
      both central and peripheral mechanisms, and the enhancement of cutaneous
      vasodilation was possibly due to a central mechanism. Enhancement of heat loss
      responses via central mechanisms was greater during the mid-luteal phase than in
      the mid-follicular phase because the elevation of female reproductive hormone
      levels during the mid-luteal phase was relatively low in T group.

PMID- 15864637
TI  - Indications and technique of central pancreatectomy-early and late results.
AB  - BACKGROUND AND AIM: Central pancreatectomy (CP) is an operation that allows one
      to resect benign or low grade malignant tumours located in the pancreatic isthmus
      that are not suitable for enucleation. The main advantage of this operation
      compared with major resections is that it permits to spare normal pancreatic
      parenchyma. PATIENTS AND METHODS: The operation is carried out by exposition of
      the pancreatic neck involved by the lesion. Thereafter, the gland is dissected
      from the splenic artery and porto-mesenteric axis and divided with a 1 cm clear
      margin. The cephalic stump is sutured, and the distal stump is anastomosed end-to
      end or end-to-side with a Roux-en-Y jejunal loop. We treated 20 patients with
      this technique. The indications for CP were: serous cystadenoma in seven
      patients, mucinous in three, solid cystic papillary tumour in one, metastasis
      from renal cancer in one and endocrine tumour in eight patients. RESULTS:
      Mortality rate was 0% and morbidity rate was 35%; pancreatic fistulas occurred in
      25% of the cases and were treated conservatively. Results of postoperative
      endocrine and exocrine function tests were normal in all controlled patients. All
      the patients are alive without evidence of local recurrence. CONCLUSION: CP is a
      safe technique for benign or low-grade malignant tumours of the pancreatic neck
      that allows one to cure the tumour with evident functional results without
      increasing the risk to the patient.

PMID- 15864638
TI  - AtGLR3.4, a glutamate receptor channel-like gene is sensitive to touch and cold.
AB  - The Arabidopsis genome encodes for 20 members of putative ligand-gated channels,
      termed glutamate receptors (GLR). Despite the fact that initial studies suggested
      a role for GLRs in various aspects of photomorphogenesis, calcium homeostasis or
      aluminium toxicity, their functional properties and physiological role in plants
      remain elusive. Here, we have focussed on AtGLR3.4, which is ubiquitously
      expressed in Arabidopsis including roots, vascular bundles, mesophyll cells and
      guard cells. AtGLR3.4 encodes a glutamate-, touch-, and cold-sensitive member of
      this gene family. Abiotic stress stimuli such as touch, osmotic stress or cold
      stimulated AtGLR3.4 expression in an abscisic acid-independent, but calcium
      dependent manner. In plants expressing the Ca(2+) -reporter apoaequorin,
      glutamate as well as cold elicited cytosolic calcium elevations. Upon glutamate
      treatment of mesophyll cells, the plasma membrane depolarised by about 120 mV.
      Both glutamate responses were transient in nature, sensitive to glutamate
      receptor antagonists, and were subject to desensitisation. One hour after
      eliciting the first calcium signal, a 50% recovery from desensitisation was
      observed, reflecting the stimulus-induced fast activation of AtGLR3.4
      transcription. We thus conclude that AtGLR3.4 in particular and GLRs in general
      could play an important role in the Ca(2+) -based, fast transmission of
      environmental stress.

PMID- 15864639
TI  - Decreased gap junctional communication in neurobiotin microinjected lens
      epithelial cells after taxol treatment.
AB  - The aim of the study was to examine gap-junction-mediated intercellular
      communication after experimentally induced aggregations of microtubules in
      cultured bovine lens epithelial cells. Intercellular communication between lens
      cells appears to be crucial for normal lens homeostasis. However, investigations
      on the maintenance of direct ion and metabolite exchange via gap junctions and
      its quantified dependency of cytoskeletal microtubules have not been available
      under conditions leading to bundling of microtubules. Thus, metabolic coupling of
      neighboring lens epithelial cells was quantified following microinjections of
      neurobiotin into single cells under various conditions. In controls, intensive
      gap-junction-mediated intercellular communication could be documented by dye
      spreading of microinjected neurobiotin. In contrast, taxol treatment for 1-3 days
      impaired, but did not completely block gap-junction-mediated intercellular
      communication. After depletion of taxol, a complete recovery of intercellular
      communication was achieved. In addition, confocal laser scanning microscopy and
      rapid-freeze deep-etch electron microscopy revealed a displacement of actin
      filaments from the perinuclear cytoplasm, accompanied by an abnormal aggregation
      of microtubules after taxol treatment, including impeded translocation of
      connexin 43 from the cytoplasm into the plasma membrane. Incubation of cells with
      nocodazole destroyed the microtubule network, accompanied by a clear reduction of
      plasma-membrane-integrated connexin 43 and significant impairment of dye
      spreading. Thus, in lens epithelial cells intercellular communication at gap
      junctions made by connexin 43 depends on the integrity of the microtubule network
      through the translocation of connexins to the plasma membrane.

PMID- 15864640
TI  - The axon arbourisation of nuclei isthmi neurons in the optic tectum of the chick
      and pigeon. A Golgi and anterograde tracer-study.
AB  - The optic tectum is reciprocally connected to the nuclei isthmi pars
      magnocellularis (Imc) and pars parvocellularis (Ipc), which have different
      modulatory effects on optic transmission. We studied the axon arbourisation of
      these isthmic nuclei in the optic tectum in order to differentiate between them
      using Golgi-impregnated preparations both in chickens and pigeons. In addition,
      sections from animals injected with the anterograde tracer biotinylated dextran
      amine (BDA) into the Imc were examined in the bright-field and electron
      microscope to identify the axon arbourisations and terminals. Also, GABA
      immunogold stained sections were examined in the electron microscope. In Golgi
      preparations, slab-like (or poplar tree-like) axon terminal arbourisations of
      both magnocellular and parvocellular isthmic nuclei neurons were found extending
      to the tectal surface, with similar branching patterns, but different lengths.
      The axon arbourisations extending from layer 5 of the optic tectum to the surface
      were termed type 1, whereas those extending from the internal (12-11) layers to
      the tectal surface were termed type 2. Type 2 arbourisations very closely matched
      arbourisations observed in BDA injected material, indicating that Imc neurons
      gave rise to type 2 arbourisations. The two kinds of axon arbourisation in the
      external tectal layers were alike in both types of bird, except for the width,
      which was about 10 mum larger in the type 2 axon arbour. Controlling for size,
      there was no significant difference between chicks and pigeons. The significance
      of these afferents in the optic tectum is discussed.

PMID- 15864641
TI  - Mophometric study of the aortic arch and its major branches in rat fetuses on the
      21st day of gestation.
AB  - The anatomy and embryology of the aortic arch and its branching tributaries
      (brachiocephalic trunk, left common carotid artery and left subclavian artery) in
      man and animals are well substantiated. However, the anatomical variations and
      morphometry of the aortic arch and its branching tributaries in rat fetus at the
      21st gestation day have not been studied. Pregnant rats were hysterectomized and
      the arterial systems of 114 fetuses were injected with a polymerisable resin
      through the umbilical artery. After maceration, the vascular casts were dissected
      out and prepared for observations under a scanning electron microscope (SEM). The
      resulting SEM pictures were studied with a picture analyser and different vessel
      parameters (diameters, lengths and angles) were measured. The success rate of the
      microvascular cast injection was 46.5%. Out of the 53 observed aortic arch casts,
      98.1% showed the classical branching pattern and one (1.9%) had no
      brachiocephalic trunk. Morphological analysis showed many differences, which were
      not linked to the litter. The statistical processing of the measurements enabled
      us to determine that the aorta diameter after the branching of the left
      subclavian artery was the most replicable parameter. Moreover, the results
      revealed some strong correlations between different parameters. There are
      probably no discrete categories among the various observed parameters as
      diameters and angles. Some parameters show very little variability and can thus
      be used as reference points for further studies such as the comparison of a
      control population with a population treated with a relevant xenobiotic.

PMID- 15864642
TI  - Prenatal evaluation of kidney function in mice using dynamic contrast-enhanced
      magnetic resonance imaging.
AB  - Glomerular differentiation starts as soon as embryonic stage 12 in mice and
      suggests that kidneys may be functional at this stage. Dynamic contrast-enhanced
      magnetic resonance microscopy, a noninvasive imaging technique, was used to
      assess renal function establishment in utero. Indeed, in adults (n = 3), an
      intravenous injection of gadolinium-DOTA induced in a first step a massive and
      rapid drop in kidney signal intensity followed, in a second step, by a drop in
      bladder signal intensity. The delay in signal changes between kidney and bladder
      reflected glomerular filtration. Pregnant mice underwent anatomical and dynamic
      contrast-enhanced magnetic resonance microscopy on postcoital days 12-13 (n = 2),
      13-14 (n = 1), 14-15 (n = 3), 15-16 (n = 2), 16-17 (n = 3), 17-18 (n = 3), and 18
      19 (n = 1). Kidneys and bladder were unambiguously depicted prior to contrast
      agent injection on stage 15-16 embryos. Contrast agent injection allowed kidney,
      detection as early as stage 12-13 but not bladder. Kinetics of signal changes
      demonstrated that glomerular filtration is established at embryonic stage 15-16
      in mice. Thus, anatomical and dynamic contrast-enhanced magnetic resonance
      microscopy may be a powerful noninvasive method for in vivo prenatal
      developmental and functional studies.

PMID- 15864643
TI  - Early neonatal dexamethasone treatment for prevention of bronchopulmonary
      dysplasia. Randomised trial and meta-analysis evaluating the duration of
      dexamethasone therapy.
AB  - The aim of the aborted trial was to determine whether the short early
      dexamethasone (DX) given after the birth improves the early outcome. We also
      reviewed the evidence (meta-analysis) to determine whether the duration of early
      DX treatment influences the early outcome, particularly in terms of
      bronchopulmonary dysplasia (BPD). The participants of the randomised multicentre,
      double-blinded placebo-controlled trial had a birth weight 500-999 g, gestation <
      or = 31.0 weeks, and respiratory failure by the age of 4 h. The infants received
      either four doses of DX (0.25 mg/kg at 12 h intervals) or placebo. The meta
      analysis was performed to determine the beneficial and adverse effects of early
      short (<96 h duration) versus early prolonged (>96 h) DX treatment. The trial was
      discontinued after 109 infants had been enrolled. There was a non-significant
      improvement in the outcome (survival without BPD, severe intracranial haemorrhage
      or periventricular leukomalacia; RR 1.27; 95% CI 0.87-1.85). The risks for
      gastrointestinal perforation and hyperglycaemia tended to increase. A total of 15
      trials were included in the meta-analysis: 10 involved prolonged (i.e. >96 h;
      1594 infants) and five short interventions (1069 infants). Early prolonged DX
      decreased the RR for BPD to 0.72 (95% CI 0.61-0.87), whereas early short DX
      course did not significantly decrease the risk (RR 0.82; 95% CI 0.64-1.05).
      Gastrointestinal haemorrhages and perforations were significantly increased only
      in the early prolonged DX group. CONCLUSION: The dosage and duration of early
      corticosteroid given to small premature infants influences the risk of the side
      effects and the early outcome.

PMID- 15864644
TI  - The efficacy of trastuzumab in Her-2/neu-overexpressing metastatic breast cancer
      is independent of p53 status.
AB  - PURPOSE: Her-2/neu and p53-mediated signalling have been shown to interact at
      various cellular levels. However, the clinical relevance of p53 alterations in
      patients receiving trastuzumab for Her-2/neu-overexpressing metastatic breast
      cancer (MBC) remains unknown. The present study was performed to corroborate
      previous in vitro findings from our laboratory showing that trastuzumab induces
      growth arrest and apoptosis in a p53-independent manner. METHOD: Retrospective
      immunohistochemical (IHC) analysis for p53 protein expression was carried out on
      tumour specimens from 104 patients receiving trastuzumab-based treatment for Her
      2/neu-overexpressing MBC at a single institution. p53 status was correlated with
      response (R) and clinical benefit (CB), median progression-free survival (PFS)
      time and overall survival (OAS) time in univariate and multivariate analyses.
      RESULTS: Characteristics were similar between p53-negative and p53-positive
      tumours (all P>0.05). In univariate analyses, R (39% vs 26%, P=0.208), CB (70% vs
      57%, P=0.218), PFS (6.2 months vs 4.2 months, P=0.186) and OAS (23.8 months vs
      23.2 months, P=0.650) were similar for p53-positive tumours and p53-negative
      tumours, respectively. In multivariate analyses, p53 status was not a significant
      predictor of R, CB, PFS or OAS (all P>0.05). CONCLUSIONS: p53 status, as
      determined by IHC, is not a predictor of the clinical efficacy of trastuzumab
      based treatment in patients with Her-2/neu-overexpressing MBC.

PMID- 15864645
TI  - Transfection of thymidine phosphorylase cDNA to human hepatocellular carcinoma
      cells enhances sensitivity to fluoropyrimidine but augments endothelial cell
      migration.
AB  - PURPOSE: To investigate the effects on sensitivity to fluoropyrimidine and
      endothelial cell (EC) migration by transfection with thymidine phosphorylase (TP)
      cDNA to a hepatocellular carcinoma (HCC) cell line SMMC-7721. METHODS: SMMC-7721
      was transfected with pcDNA3.1/zeo (+) with human TP cDNA. TP mRNA expression was
      determined by RT-PCR. Sensitivity to fluoropyrimidine was determined by 3-[4,5
      dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Induction of
      EC migration was detected by Boyden chamber assay. RESULTS: The construction of
      pcDNA3.1/zeo(+)-TP was verified by digestion with restriction endonuclease Apa1.
      When comparison was made between SMMC-7721 cell clone transfected with
      pcDNA3.1/zeo(+)-TP (S-TP) and control clone transfected with pcDNA3.1/zeo(+) (S
      vector), we found that TP mRNA expression level was much higher in S-TP, being
      2.09+/-0.16 vs 0.48+/-0.06 in S-vector (P < 0.01), sensitivity to 5'-deoxy-5
      fluorouridine (5'-dFUrd, a prodrug of 5-fluorouracil) in S-TP was significantly
      enhanced compared with that in S-vector (IC(50); 56.81+/-9.85 micromol/l vs
      162.25+/-11.03 micromol/l, P < 0.01), and the culture medium of S-TP possessed
      more potential to induce EC migration than that of S-vector (the number of ECs
      appearing on the outer surfaces of the membrane was 275+/-29 vs 122+/-35 per
      field, P < 0.01). CONCLUSION: Sensitivity to 5'-dFUrd could be enhanced by
      transfection with TP cDNA for SMMC-7721 cells. However, EC migration was also
      promoted at the same time. Therefore, transfection with TP alone might have no
      potential to enhance anti-tumoral effects of fluoropyrimidine in HCC.

PMID- 15864646
TI  - Morphology of the puparia of the housefly, Musca domestica (Diptera: Muscidae)
      and blowfly, Chrysomya megacephala (Diptera: Calliphoridae).
AB  - Examination of the puparia of the housefly, Musca domestica L. and blowfly
      Chrysomya megacephala (F.), through scanning electron microscopy (SEM), revealed
      many differences in the profile of their morphology. Special attention was
      focused on puparial characteristics used to differentiate between the two fly
      species studied, and between other forensically important flies. Results of this
      study indicate that the housefly puparia are almost evenly rounded at both ends
      and the anterior spiracle bears six papillae. A pair of pupal respiratory horns
      is found laterally before the posterior boundary of the first abdominal segment,
      bearing numerous papillae that have a longitudinal opening along the oval convex
      base. The peritreme of each posterior spiracle forms a crude forward or reverse D
      shape, encircling three sinuous slits. The blowfly pupariums anterior spiracle
      contains 8-12 papillae. The pupal respiratory horns protrude slightly and in some
      specimens a group of approximately 38 globules on the bubble-like membrane may be
      observed. Each of the posterior spiracles is more or less an oval- shaped
      peritreme, encircling three straight spiracular slits. The anatomical features
      presented herein allow for the differentiation of puparia of the two fly species
      studied and could prove useful in future forensic entomological assessments.

PMID- 15864647
TI  - CO(2)-fixing enzymes during moulting from third larval to fourth larval stage of
      Anisakis simplex and Hysterothylacium aduncum (Nematoda: Anisakidae).
AB  - The fixing of CO(2) is an important metabolic process for many organisms. In the
      anisakid nematodes, CO(2) has been shown to be necessary for their development,
      at least in vitro. The presence of CO(2) stimulates the moulting (M3) of the
      larvae from the third (L3) to the fourth (L4) stage and prolongs the survival, at
      least, in vitro. We determined the activity of CO(2)-fixing enzymes, common to
      many organisms, in two anisakids: Anisakis simplex, a parasite of cetaceans, and
      Hysterothylacium aduncum, a parasite of fish. Although no activity was detected
      for pyruvate carboxylase or carboxylating-malic enzyme, we detected
      phosphoenolpyruvate carboxykinase (PEPCK) and phosphoenolpyruvate carboxylase
      (PEPC) activity. In A. simplex, PEPCK was clearly higher than that of PEPC
      throughout the moulting process studied. In H. aduncum, although the activity of
      both enzymes was of similar magnitude, they showed different behaviour; PEPCK
      activity decreased after the moulting to L4, PEPC activity increased so that the
      ratio PEPCK/PEPC activity decreased from 1.90 before moulting to 0.59 after.

PMID- 15864648
TI  - First record of Progrillotia dasyatidis Beveridge Neifar and Euzet, 2004
      (Cestoda: Trypanorhyncha) plerocerci from Teleost fishes off the Portuguese
      coast, with a description of the surface morphology.
AB  - Plerocerci of Progrillotia dasyatidis Beveridge et al. (2004), family
      Progrillotiidae Palm (2004), are reported from several teleost fishes off the
      Portuguese coast, giving a first insight into the life cycle biology of these
      unique trypanorhynchs. The first description and assignment of the plerocercus to
      P. dasyatidis is based on morphological features, such as scolex and bothria
      morphology and tentacular hook arrangement, and is expanded to incorporate the
      surface morphology, examined by scanning electron microscopy, constituting the
      first ultrastructural study for a species within this family. Comparisons with
      other species of the genus Progrillotia are made, based on the scolex and bothria
      morphology and tentacular hook arrangement, in order to give an overview into the
      variability within this genus, whereas comparisons with adults from the same
      species evidence the variability within the same species. The systematic
      approaches of Campbell and Beveridge (1994) and Palm (1997, 2004) are discussed
      and emphasis is placed on the utility of microtriches and the characteristic life
      cycle within the genus as systematic characters.

PMID- 15864650
TI  - Role of small GTPases in Trypanosoma cruzi invasion in MDCK cell lines.
AB  - Trypanosoma cruzi can modulate a large number of host intracellular responses
      during its invasion. GTPases such as RhoA, Rac1 and Cdc42 are examples of
      molecules that could be activated at this moment and trigger changes in the
      pattern of F-actin cytoskeleton leading to the formation of structures like
      stress fibers, lamellipodium and fillopodium, respectively. Here we investigate
      the role of these GTPases in the cytoskeletal rearrangement of MDCK cell
      transfectants expressing variants of RhoA, Rac1 and Cdc42 during T. cruzi
      infection. The adhesion, internalization and the survival rate were determined.
      Rac1 mutants showed the higher adhesion and internalization indexes but the lower
      survival index after 48 h of infection. Confocal laser scanning microscopy showed
      changes in the pattern of F-actin distribution and reorganization at the site of
      trypomastigote invasion. These observations suggest that these GTPases act in the
      signaling mechanisms that affect the F-actin cytoskeleton during T. cruzi
      invasion.

PMID- 15864649
TI  - The trypanosome alternative oxidase exists as a monomer in Trypanosoma brucei
      mitochondria.
AB  - The bloodstream forms of African trypanosomes solely depend on trypanosome
      alternative oxidase (TAO), for respiration. Similar to alternative oxidases
      (AOXs) found in plants and fungi, TAO is a membrane-bound diiron protein. Here,
      we investigated if TAO exists as a dimer like plant AOXs, or as a monomer like
      that of fungi. We have found that TAO forms a homo-dimer on a regular SDS-PAGE in
      the absence of any reducing agent and exists as a monomer under reducing
      condition. However, TAO does not form a dimer upon treatment of mitochondria with
      diamide. TAO was found as a higher molecular mass complex on a Blue-native gel
      after solubilization with digitonin. In the detergent soluble form, TAO activity
      was stimulated under reducing and inhibited under oxidizing condition. However,
      these conditions have no effect on the TAO activity in the mitochondria.
      Moreover, chemical cross-linking analysis revealed that TAO could not be cross
      linked when present in the mitochondria. Together, it suggests that like certain
      other hydrophobic membrane proteins, TAO forms a dimer or oligomer when
      solubilized with detergents, and the TAO-dimer is SDS-resistant. However, it
      exists as a monomer in Trypanosoma brucei mitochondria.

PMID- 15864651
TI  - Efficacy of amodiaquine in uncomplicated falciparum malaria in Nigeria in an area
      with high-level resistance to chloroquine and sulphadoxine/pyrimethamine.
AB  - Falciparum Malaria is hyperendemic in southern Nigeria and chloroquine resistance
      is an increasing problem. Therefore, the parasitological and haematological
      response to treatment with amodiaquine was studied in children under 5 years
      during a 14-day follow-up. Of 105 children who accomplished the study (out of 114
      who were enrolled), 95.3% were parasite-negative on thick blood film on day 7,
      which decreased to 89.5% on day 14. The haemoglobin levels increased on average
      by 1.3% on day 14 (+/-1.9) and more pronounced in children with anaemia<10 g/dl
      on enrollment. The number of patients with adverse events (mainly pruritus and
      nausea) was few. This study shows that amodiaquine is effective, safe and
      affordable in an area with high resistance to chloroquine.

PMID- 15864652
TI  - The Kavar(D) dominant female-sterile mutations of Drosophila reveal a role for
      the maternally provided alpha-tubulin4 isoform in cleavage spindle maintenance
      and elongation.
AB  - The dominant-negative female-sterile Kavar(D) mutations and their revertant
      kavar(r) alleles identify the alphaTubulin67C gene of Drosophila melanogaster,
      which codes for the maternally provided alpha-tubulin(4) isoform. The mutations
      result in the formation of monopolar, collapsed spindles (each with two nearby
      centrosomes, a tassel of microtubules and overcondensed chromosomes), thus
      revealing a novel function for alpha-tubulin(4) in spindle maintenance and
      elongation. Molecular features of the two Kavar(D) alleles and a kavar(null)
      allele are described and models for their actions are discussed.

PMID- 15864653
TI  - Characteristics of children with primary hypertension seen at a referral center.
AB  - Primary hypertension is well known to occur in children, but the characteristics
      of such children are changing due to the influence of the obesity epidemic. In
      view of this, we conducted a cross-sectional study of 70 children [age 13.3+/-4
      years (mean +/- SD)] with primary hypertension referred to a specialized
      pediatric hypertension clinic. Secondary hypertension had been excluded after a
      standardized diagnostic evaluation. Isolated systolic hypertension was present in
      62.9% of subjects. Family history of hypertension was present in 86.2%, and 52.9%
      were obese (BMI > or =95th percentile). BMI was weakly correlated with systolic
      BP (r =0.28,P =0.10) and was significantly correlated with total cholesterol (r
      =0.36,P =0.005) and triglycerides (r =0.42,P =0.01). Mean plasma renin activity
      (PRA) was 3.1+/-2.7 ng/ml/h. PRA was correlated with diastolic but not systolic
      BP. Patients with high PRA had higher diastolic BP and lower BMI compared to
      those with low PRA. Left ventricular hypertrophy was present in 24%. Mean 24-h
      systolic BP load by ambulatory BP monitoring was 52+/-24%; mean 24-h diastolic BP
      load was 18+/-16%; BP loads were greater in patients with high PRA. These data
      suggest that primary hypertension in children is characterized by systolic BP
      elevation, positive family history and obesity. Hyperlipidemia accompanies
      primary hypertension in obese children, and left ventricular hypertrophy is
      common. Patients with high PRA have more severe BP elevation. Future studies
      should focus on further defining the pathophysiology of primary hypertension in
      children, including the roles of renin and insulin resistance, so that improved
      methods of prevention and treatment can be developed.

PMID- 15864654
TI  - Maternal pregnancy vomiting and offspring salt taste sensitivity and blood
      pressure.
AB  - The purpose of this study was to investigate the relationship between salt taste
      perception and blood pressure (BP) in normotensive adolescents as modified by
      maternal fluid losses during the first trimester of gestation. Seventy-two
      healthy adolescents (42 boys) aged between 9.0-21.1 years, recruited from the
      population-based RICARDIN study, were included. A maternal questionnaire about
      the duration of pregnancy, birth weight and vomiting or diarrhoea in the first
      trimester of gestation was collected. The sample was categorized into: "vomiter
      descendents", those whose mother reported significant vomiting in the first
      trimester of gestation and "non-vomiter descendents" the remaining. Height,
      weight, and standardised BP measurement were recorded. Salt gustatory performance
      was assessed using a behavioral sensitivity test to determine the lower NaCl
      gustatory threshold, and a behavioral discrimination test, measuring the ability
      to distinguish among different saline solutions. Salt taste sensitivity showed a
      significant correlation with systolic BP (SBP) in "vomiter descendents" ( r = 
      0.66; P =0.003), but not in "non-vomiter descendents". Adjusted by gender, and
      actual height and weight, salt sensitivity performance remained significantly
      related to SBP. An association between descendents' SBP and maternal vomiting
      during gestation exists, adding a new element of evidence to the "Barker
      hypothesis".

PMID- 15864655
TI  - Urinary diversion in children and adolescents with neurogenic bladder: the Mainz
      experience. Part III: Colonic conduit.
AB  - After the failure of conservative treatment of neurogenic bladders, urinary
      diversion has to be considered. For patients with chronic renal failure, severe
      dilated upper urinary tracts with deterioration of the renal function and those
      who are not able to perform a self-catheterization, the colonic conduit diversion
      is our therapy of choice. In this part of the study, we investigate the long-term
      safety of our concept for these patients in regard to protecting the upper
      urinary tracts. Between 1968 and 2002, colonic conduit urinary diversion was
      performed in 88 patients, in most of them in the era before continent diversion.
      Overall, 11 patients with a colonic conduit were converted to bladder
      substitution or continent cutaneous diversion during the follow-up period. These
      patients are no longer included in the long-term follow-up of colonic conduit
      patients. Of the 77 patients with colonic conduit diversion, 21 patients were not
      available for follow-up: 11 were deceased and 10 were lost to follow-up. Three of
      the deaths were related to nephrological complications in patients who already
      had impaired renal function before conduit diversion. An average follow-up of
      21.8 years (2-32.7; median 23.8 years.) is available in 56 patients with 99 RUs
      (6 solitary kidneys, 7 nephrectomies). Five non-functioning kidneys were removed
      after recurrent pyelonephritis and two kidneys with pyonephrosis. Ureter stenoses
      were corrected in 6% of the RUs. As compared to preoperatively, the upper urinary
      tracts remained stable or improved in 97/99 RUs at the latest follow-up. A
      revision of the stoma was necessary in 16% (conduit elongation n =2, stenosis n
      =7) and calculi formations were treated in 8% of the RUs. For patients with
      chronic renal failure or who are unable to perform a catheterization of a
      continent stoma, the colonic conduit is a safe alternative in the long run.

PMID- 15864656
TI  - Urinary diversion in children and adolescents with neurogenic bladder: the Mainz
      experience. Part II: Continent cutaneous diversion using the Mainz pouch I.
AB  - After failure of conservative treatment of neurogenic bladders (deterioration of
      the upper urinary tract/incontinence) continent cutaneous diversion has to be
      considered in those patients with irreparable urethral sphincter defects or those
      who are unable to perform trans-urethral self-catheterization. In this second
      part of the study we investigated the long-term safety of using the Mainz pouch I
      with regard to protecting the upper urinary tracts and to provide urine
      continence. Between 1985 and 2002, operations to form an ileocaecal pouch with
      umbilical stoma (Mainz pouch I) were performed on 70 children and adolescents of
      median age 15.3 years (range 5.7-20 years). During the follow-up period five
      patients died 2.4-14 years postoperatively of causes not related to urinary
      diversion. A follow-up period of 8.7 years (0.9-18) was achieved in 65 patients
      with 118 renal units (RUs). As compared to preoperatively, the upper urinary
      tracts had remained stable or improved in 113/118 RUs (95.8%) at the latest
      follow-up. Complete continence was achieved in 97% of patients with a continent
      cutaneous diversion. Surgical revisions were required for: incontinence of the
      outlet mechanism in 9%, stoma prolapse in 2%, stoma stenosis in 23%, pouch
      calculi in 15%, symptomatic reflux in 1%, ureter stenosis in 16% of the RUs with
      submucosal tunnel and in 3% of the RUs with an extramural tunnel. We conclude
      that, in patients with irreparable sphincter defect and those who are unable to
      perform urethral self-catheterization, continent cutaneous urinary diversion with
      the Mainz pouch I provides a high continence rate with preservation of the upper
      urinary tracts in the long run. In patients with dilated ureters, the extramural
      tunnel technique results in a lower complication rate.

PMID- 15864657
TI  - Treating sialorrhea with transdermal scopolamine. Exploiting a side effect to
      treat an uncommon symptom in cancer patients.
AB  - INTRODUCTION: Sialorrhea is a distressing symptom accompanying oral cancer and
      many heterogeneous cancer-related conditions (chemotherapy-induced nausea, bowel
      subocclusion, pharmacologic side effects), but its incidence is low in cancer
      patients. Conversely, it is frequent in patients with neurological damage, and
      some therapeutic options have been attempted such as botulinum toxins,
      anticholinergic agents, and surgical procedures. CASE REPORT: We report the case
      of an 80-year-old woman with peritoneal carcinomatosis and bowel subocclusion,
      suffering from distressing nausea and sialorrhea that rapidly improved using
      transdermal scopolamine. No relevant side effects occurred during the treatment,
      and the reduction of the abnormal salivation allowed the recovery of oral
      feeding. CONCLUSIONS: Anticholinergic drugs are classified as secondary options
      in the treatment of sialorrhea of patients with Parkinson's disease or cerebral
      palsy, owing to the relevant side effects occurring during prolonged treatments.
      However, they could be useful in cancer patients with bowel subocclusion, as the
      reduction of gastrointestinal secretions and intestinal motility (frequent side
      effects of anticholinergic drugs) could be effective in controlling nausea,
      vomiting, and abdominal pain. Moreover, the transdermal or sublingual route of
      administration can be of some interest, avoiding other more invasive parenteral
      approaches.

PMID- 15864658
TI  - Neoplastic fever: a neglected paraneoplastic syndrome.
AB  - Neoplastic fever, a paraneoplastic syndrome caused by cancer itself, represents a
      diagnostic challenge for the clinician and is an important issue in supportive
      oncology. Timely recognition of this febrile condition by differentiating it from
      other cancer-associated fevers, such as infection and drug reaction, is essential
      for effective patient management. Although the pathophysiology of neoplastic
      fever is not well understood, it is suspected to be cytokine mediated. In
      clinical practice, when a patient with cancer presents with unexplained fever,
      extensive diagnostic studies are needed to differentiate neoplastic fever from
      nonneoplastic fever. Only after excluding identifiable etiologies of fever can
      the diagnosis of neoplastic fever be suspected. According to our experience, the
      naproxen test is a safe and useful test in differentiating neoplastic fever from
      infectious fever in patients with cancer. In addition, naproxen and other
      nonsteroidal anti-inflammatory drugs have been effective in the management of
      neoplastic fever and offer a significant palliative benefit for the patient.

PMID- 15864659
TI  - The relationship between fatigue and light exposure during chemotherapy.
AB  - BACKGROUND: Fatigue is one of the most common and distressing complaints among
      cancer patients, not only during radiation and chemotherapy, but also for months
      to years after the completion of treatment. Fatigue interferes with patients'
      daily lives, reduces their quality of life, and is often a significant reason why
      patients discontinue treatment. We hypothesized that some of the fatigue may be
      related to disrupted circadian rhythms and low light exposure. The main objective
      of this study therefore was to investigate the association between fatigue and
      light exposure among patients with breast cancer. METHODS: As part of a larger,
      ongoing prospective study on fatigue, sleep, and circadian rhythms in patients
      with breast cancer, an analysis of 63 women newly diagnosed with stage I-IIIA
      breast cancer and scheduled to receive four cycles of adjuvant or neoadjuvant
      anthracycline-based chemotherapy was conducted. Data were collected before and
      during weeks 1, 2, and 3 of cycle 1 and cycle 4. Fatigue was assessed using the
      Short Form of Multidimensional Fatigue Symptom Inventory. Light exposure was
      recorded with a wrist actigraph. RESULTS: There were significant correlations
      between fatigue levels and light exposure (r=-0.28 to -0.45) within both cycle 1
      and cycle 4, such that higher levels of fatigue were associated with less light
      exposure. There were also significant correlations between changes in light
      exposure and changes in fatigue within the first 2 weeks of each cycle (r=-0.28
      to -0.52). CONCLUSIONS: Increased fatigue was significantly correlated with
      decreased light exposure among patients with breast cancer. Although the cause
      and effect of exacerbated fatigue and decreased light exposure cannot be
      confirmed by the current study, and lower light exposure may just in part be due
      to the fatigued patients spending less time outdoors in bright light, two
      hypotheses are proposed about the mechanisms by which light may alleviate the
      fatigue of patients with breast cancer. These results suggest the need for
      prospective intervention studies of light therapy for breast-cancer-related
      fatigue.

PMID- 15864660
TI  - Assessment and treatment of symptoms among Italian medical oncologists.
AB  - OBJECTIVES: This work was conducted to evaluate symptoms assessment and use of
      patient-tailored protocols in clinical practice among Italian medical
      oncologists. METHODS: A questionnaire based on four topics (assessment of
      symptoms, assessment of a specific symptom, assessment of pain, use of patient
      tailored protocols of treatment) was administered to 250 Italian medical
      oncologists. RESULTS: Of these oncologists, 43.7% used multiple symptoms tools
      and 37.9% used symptom specific tools; 58.9% used some instrument to assess pain.
      More than a third of the respondents (35.5%) used patient-tailored protocols. No
      statistical differences were found regarding region of residency, availability of
      consultants in pain therapy and/or palliative care, colleagues with main interest
      on palliative care, and beds dedicated to palliative care. Statistically
      significant differences were found regarding the position (staff/resident) in
      three out four topics. CONCLUSIONS: Among Italian medical oncologists, the
      instruments used for assessment of symptoms are poorly employed. Even when these
      instruments are used, patient-tailored protocols are rarely administered.

PMID- 15864661
TI  - Family functioning and psychological distress among Japanese breast cancer
      patients and families.
AB  - GOALS OF WORK: The purpose of this study was to develop a typology of family
      functioning in the families of breast cancer patients. PATIENTS AND METHODS:
      Seventy-four families (189 individuals: 74 patients, 54 spouses, 46 offspring,
      and 15 other relatives) completed self-report questionnaires. Perception of
      family functioning was assessed using the family relationship index (FRI) and its
      three dimensions (cohesiveness, expressiveness, and conflict) and was classified
      into groups by a cluster analytic approach. Psychological distress was assessed
      using the Zung self-rating depression scale (SDS) and the Zung self-rating
      anxiety scale (SAS). MAIN RESULTS: Cluster analysis yielded three groups of
      patients and their family members: one cluster with high cohesiveness, high
      expressiveness, and low conflict ("supportive" type: n=64); a second group with
      low cohesiveness, low expressiveness, and high conflict ("conflictive" type:
      n=65); and a third group with limited cohesiveness, limited expressiveness, and
      low conflict ("intermediate" type: n=60). Analysis of variance revealed that
      conflictive families manifested the highest level of depression and anxiety among
      these clusters. CONCLUSIONS: Typology of family functioning can identify
      psychologically at-risk families. A family-focused approach can help to reduce
      psychological distress, especially in conflictive families.

PMID- 15864662
TI  - Life before death: identifying preparatory grief through the development of a new
      measurement in advanced cancer patients (PGAC).
AB  - GOALS OF WORK: This paper describes the development of a self-rating scale to
      measure preparatory grief in advanced cancer patients. PATIENTS AND METHODS: The
      Preparatory Grief in Advanced Cancer patients (PGAC) instrument incorporates
      seven multi-items scales. The final sample consisted of 200 patients. The
      questionnaire was completed at baseline and 3 days later with a cross-validation
      sample of 100 patients. MAIN RESULTS: The average time required to complete the
      questionnaire was 9 min. All scales met the minimum standards of reliability
      (Cronbach's alpha coefficient >0.70). The test-retest reliability in terms of
      Spearman-rho coefficient was also satisfactory (p < 0.05). Validity was
      demonstrated by content validity, factor analysis, convergence and discriminative
      validity, inter-scales correlations, concurrent validity with the Hospital
      Anxiety and Depression Scale (HADS) and known-group validity with the Eastern
      Cooperative Oncology Group (ECOG) performance status. CONCLUSIONS: The PGAC is a
      reliable and valid measure for the assessment of anticipatory grief in patients
      with advanced stage cancer.

PMID- 15864663
TI  - Patients with haematological malignancies requiring invasive mechanical
      ventilation: differences between survivors and non-survivors in intensive care
      unit.
AB  - BACKGROUND: Mortality of patients with haematological malignancies requiring
      intensive therapy is high. We wanted to establish reasons for intensive care unit
      (ICU) admission and treatment as well as outcome in subjects who required
      invasive mechanical ventilation. We were also interested in differences between
      ICU survivors and non-survivors at the moment of admission. PATIENTS AND METHODS:
      Forty patients (21 women and 19 men) were included in the study. Median of age
      was 42 (range 16-73) years. All patients required mechanical ventilation. We
      analysed age, gender, disease character (acute/chronic), diagnosed pneumonia,
      multiple organ failure (MOF), history of bone marrow transplantation, peripheral
      blood parameters (leukocyte, neutrocyte, erythrocyte and thrombocyte counts,
      haemoglobin level and haematocrit), mean arterial pressure (obtained through
      direct measurement), necessity of catecholamine administration and symptoms of
      the acute renal insufficiency at the moment of ICU admission. MAIN RESULTS: Sixty
      five percent of patients died in ICU. Intergroup comparisons between survivors
      and non-survivors revealed statistically significant differences in the presence
      of neutropenia, thrombocyte count, mean arterial pressure and the necessity of
      catecholamines administration, as well as scores obtained through patient
      evaluation according to the Acute Physiology and Chronic Health Evaluation
      (APACHE II), the Sequential Organ Failure Assessment (SOFA) and the New
      Simplified Acute Physiology Score (SAPS II) scales. Multivariate logistic
      regression revealed only one independent risk factor for ICU mortality in the
      analysed group--SAPS II score (p=0.009). Calculated value of the unitary odds
      ratio was 1.065 (95% confidence interval 1.017-1.116). CONCLUSIONS: Mortality of
      patients with haematological malignancies requiring intensive mechanical
      ventilation remains high. Scoring with the SAPS II system was a useful tool for
      determination of ICU mortality risk in those patients.

PMID- 15864665
TI  - Reviewer's Comment regarding: "Long-term effects of supervised physical training
      in secondary prevention of low back pain" (by I. Maul et al.).

PMID- 15864666
TI  - A concise follow-up of a previous report: posterior reduction and anterior lumbar
      interbody fusion in symptomatic low-grade adult isthmic spondylolisthesis.
AB  - We report the updated results for a previously evaluated surgical treatment for
      adult low-grade isthmic spondylolisthesis. In 12 patients a decompressive
      laminectomy was performed followed by a circumferential fusion using posterior
      pedicle screw instrumented reduction and staged anterior cage-assisted interbody
      fusion. Average time to follow-up was 5.6 (range 4.9-6.6) years. The average
      Oswestry Disability Index at last follow-up was 14 compared to 13 at 2.1-year
      follow-up. The average VAS score for back pain at last follow-up was 2.3 compared
      to 2.8 at 2.1-year follow-up. Ten patients had resumed their pre-symptom work
      status. This study demonstrates maintenance of the good clinical and radiological
      2.1-year outcome after 5.6-year follow-up with no deterioration of back-pain
      scores.

PMID- 15864667
TI  - Biomechanical evaluation of an expansive pedicle screw in calf vertebrae.
AB  - The main objective of the present study is to evaluate biomechanically a newly
      designed expansive pedicle screw (EPS) using fresh pedicles from calf lumber
      vertebrae in comparison with conventional pedicle screws, (CDH) CD Horizon,
      Universal Spine System pedicle screw (USS) and Tenor (Sofamor Denek). Pull-out
      and turning-back tests were performed on these pedicle screws to compare their
      holding strength. Additionally, revision tests were undertaken to evaluate the
      mechanical properties of EPS as a "rescue" revision screw. A fatigue simulation
      test using a perpendicular load up to 1,500,000 cycles was also carried out. The
      results showed that the turning back torque (Tmax) and pull-out force (Fmax) of
      EPS screws were significantly greater than those of USS, Tenor and CDH screws
      (6.5x40 mm). In revision tests, the Fmax of both types of EPS screws (6.5x40 mm;
      7.0x40 mm) were significantly greater than that of CDH, USS, and Tenor screws
      (P<0.05). Furthermore, no screws were broken or bent at the end of fatigue tests.
      The findings from the current study suggest that expansive pedicle screws can
      significantly improve the bone purchase and the pull-out strength compared to
      USS, Tenor and CDH screws of similar dimensions before and after a failure
      simulation.

PMID- 15864668
TI  - Primary liposarcoma of the thoracic spine: case report.
AB  - Liposarcoma is a malignant tumor of soft tissue. The thoracic spine is an unusual
      location, even for metastasis, and to our knowledge, no case of primary
      pleomorphic liposarcoma of the vertebral body has been reported until now. A
      female patient presented with paraplegia. She had a previous medical history of
      mental depression, and complained of dorsal pain for three months following a
      road accident. Magnetic Resonance Imaging (MRI) revealed a collapse of T7-T8, and
      the diagnosis of plasmocytoma was made. She was treated with decompressive
      laminectomy and posterior instrumentation. Histological examination revealed a
      pleomorphic liposarcoma. She received a course of radiotherapy. At 13 months
      follow-up she developed pulmonary metastases and rib involvement. The spine is an
      unusual location for pleomorphic liposarcoma, even as metastasis. The
      differential diagnoses of this rare entity are discussed, as well as the criteria
      for diagnosing primary spinal liposarcoma. Although rare, our case demonstrates
      that liposarcoma should be considered in the differential diagnosis of spinal
      tumors.

PMID- 15864669
TI  - Minimum 20-year follow-up results of Harrington rod fusion for idiopathic
      scoliosis.
AB  - We evaluated the outcome of spinal fusion with a single Harrington distraction
      rod in patients with idiopathic scoliosis. At follow-up visits a minimum of 20
      years post-surgery, we studied 24 patients who had been operated on by the same
      surgeon. The Scoliosis Research Society (SRS) Instrument and an additional
      questionnaire of our own, along with an invitation for a follow-up visit, were
      originally mailed to 28 consecutive patients of the surgeon. The SRS Instrument
      has seven domains dealing with back pain, general self-image, self-image after
      surgery, general function, function in terms of level of activity, function after
      surgery, and degree of satisfaction with the surgery. The length of time between
      surgery and the follow-up visit averaged 22.9 years (20.2-27.3). The mean age at
      surgery and follow-up were 15.8 (13-22) and 38.8 (35-48) years, respectively.
      Twenty-four patients sent back the completed questionnaires and 16 of them
      participated in the clinic and radiographic follow-up. To assess the meaning of
      the questionnaires' results, a control group of the same sex, age and geographic
      provenance was selected from our outpatients without scoliosis. The average
      follow-up score on the SRS Instrument for the patients was 100.8 (78-110). When
      we compared the study and control groups, no significant differences in the
      single SRS domain scores were observed. The mean Cobb angle and rib cage
      deformity before surgery were 70.46 degrees (40-120) and 36.4 mm (20-60 mm),
      respectively, whereas on follow-up they were 41.23 degrees (16-75) and 22.3 mm (5
      50 mm), respectively. These long-term results lead us to consider Harrington
      fusion a procedure that produces a long-lasting high degree of self-reported post
      operative satisfaction.

PMID- 15864671
TI  - Compliance of the L5-S1 spinal unit: a comparative study between an unconstrained
      and a partially constrained system.
AB  - A comparison between an unconstrained and a partially constrained system for in
      vitro biomechanical testing of the L5-S1 spinal unit was conducted. The objective
      was to compare the compliance and the coupling of the L5-S1 unit measured with an
      unconstrained and a partially constrained test for the three major physiological
      motions of the human spine. Very few studies have compared unconstrained and
      partially constrained testing systems using the same cadaveric functional spinal
      units (FSUs). Seven human L5-S1 units were therefore tested on both a pneumatic,
      unconstrained, and a servohydraulic, partially constrained system. Each FSU was
      tested along three motions: flexion-extension (FE), lateral bending (LB) and
      axial rotation (AR). The obtained kinematics on both systems is not equivalent,
      except for the FE case, where both motions are similar. The directions of coupled
      motions were similar for both tests, but their magnitudes were smaller in the
      partially constrained configuration. The use of a partially constrained system to
      characterize LB and AR of the lumbosacral FSU decreased significantly the
      measured stiffness of the segment. The unconstrained system is today's "gold
      standard" for the characterization of FSUs. The selected partially constrained
      method seems also to be an appropriate way to characterize FSUs for specific
      applications. Care should be taken using the latter method when the coupled
      motions are important.

PMID- 15864670
TI  - Effects of chronic low back pain on trunk coordination and back muscle activity
      during walking: changes in motor control.
AB  - Low back pain (LBP) is often accompanied by changes in gait, such as a decreased
      (preferred) walking velocity. Previous studies have shown that LBP diminishes the
      normal velocity-induced transverse counter-rotation between thorax and pelvis,
      and that it globally affects mean erector spinae (ES) activity. The exact nature
      and causation of these effects, however, are not well understood. The aim of the
      present study was to examine in detail the effect of walking velocity on global
      trunk coordination and ES activity as well as their variability to gain further
      insights into the effects of non-specific LBP on gait. The study included 19
      individuals with non-specific LBP and 14 healthy controls. Gait kinematics and ES
      activity were recorded during treadmill walking at (1) a self-selected
      (comfortable) velocity, and (2) sequentially increased velocities from 1.4 up to
      maximally 7.0 km/h. Pain intensity, fear of movement and disability were measured
      before the experiment. The angular movements of thorax, lumbar and pelvis were
      recorded in three dimensions. ES activity was recorded with pairs of surface
      electrodes. Trunk-pelvis coordination and mean amplitude of ES activity were
      analyzed. In addition, invariant and variant properties of trunk kinematics and
      ES activity were studied using principal component analysis (PCA). Comfortable
      walking velocity was significantly lower in the LBP participants. In the
      transverse plane, the normal velocity-induced change in pelvis-thorax
      coordination from more in-phase to more antiphase was diminished in the LBP
      participants, while lumbar and pelvis rotations were more in-phase compared to
      the control group. In the frontal plane, intersegmental timing was more variable
      in the LBP than in the control participants, with additional irregular movements
      of the thorax. Rotational amplitudes were not significantly different between the
      LBP and control participants. In the LBP participants, the pattern of ES activity
      was affected in terms of increased (residual) variability, timing deficits,
      amplitude modifications and frequency changes. The gait of the LBP participants
      was characterized by a more rigid and less variable kinematic coordination in the
      transverse plane, and a less tight and more variable coordination in the frontal
      plane, accompanied by poorly coordinated activity of the lumbar ES. Pain
      intensity, fear of movement and disability were all unrelated to the observed
      changes in coordination, suggesting that the observed changes in trunk
      coordination and ES activity were a direct consequence of LBP per se. Clinically,
      the results imply that conservative therapy should consider gait training as well
      as exercises aimed at improving both intersegmental and muscle coordination.

PMID- 15864672
TI  - Pathological mechanism of idiopathic scoliosis: experimental scoliosis in
      pinealectomized rats.
AB  - The pathological mechanism of curve progression in idiopathic scoliosis is still
      obscure. In this study we investigated the pathological mechanism of idiopathic
      scoliosis in experimentally induced scoliosis in rats. A total 30 rats were
      divided into three groups: ten bipedal rats with a sham operation, which served
      as the control; ten quadrupedal rats with pinealectomy; and ten bipedal rats with
      pinealectomy. Scoliosis developed only in pinealectomized bipedal rats and not in
      pinealectomized quadrupedal rats. Cervicothoracic lordosis developed in bipedal
      rats with or without pinealectomy. These deformities of lordoscoliosis in
      pinealectomized bipedal rats were similar to human idiopathic scoliosis. Lordosis
      or lordotic tendency was sufficient to cause the spine to rotate to the side.
      Rotational instability of the spine with rotation of lordotic segment appears to
      produce a characteristic scoliotic deformity as a secondary phenomenon. Our
      findings suggest that lordosis may develop in bipedal rats, but pinealectomy is
      required for the development of lordoscoliosis. Balanced muscle tone controlled
      by the postural reflex is important to maintain normal posture with a straight
      spine in the bipedal condition. The disturbance of equilibrium and other postural
      mechanisms secondary to a deficiency of melatonin after pinealectomy may promote
      development of lordoscoliosis with vertebral rotation especially in the bipedal
      posture.

PMID- 15864674
TI  - An empirical analysis of tobacco addiction in Italy.
AB  - We estimate tobacco demand in Italy following the rational addiction framework.
      Two empirical tests are performed. The first uses a pseudo panel of data and
      follows the approach of Baltagi and Griffin. We obtain evidence of forward
      looking behavior but implausible estimates of the discount rate. The second uses
      a time series of per capita tobacco expenditures. In this case the data support
      the theory. A simulation is also carried out to assess the effects of future
      permanent price changes on tobacco demand. The novelty here is that expected
      future consumption is estimated by ordinary least squares using past and future
      prices as regressors instead of taking actual consumption as is usually the case
      in empirical tests of the rational addiction model. Results show that
      announcements of future price changes may be effective in curbing tobacco demand.

PMID- 15864673
TI  - Structure of glutathione S-transferase of the filarial parasite Wuchereria
      bancrofti: a target for drug development against adult worm.
AB  - A three dimensional structural model of Glutathione-S-transferase (GST) of the
      lymphatic filarial parasite Wuchereria bancrofti (wb) was constructed by homology
      modeling. The three dimensional X-ray crystal structure of porcine pi-class GST
      with PDB ID: 2gsr-A chain protein with 42% sequential and functional homology was
      used as the template. The model of wbGST built by MODELLER6v2 was analyzed by the
      PROCHECK programs. Ramachandran plot analysis showed that 93.5% of the residues
      are in the core region followed by 5.4 and 1.1% residues in the allowed and
      generously allowed regions, respectively. None of the non-glycine residues is in
      disallowed regions. The PROSA II z-score and the energy graph for the final model
      further confirmed the quality of the modeled structure. The computationally
      modeled three-dimensional (3D) structure of wbGST has been submitted to the
      Protein Data Bank (PDB) (PDB ID: 1SFM and RCSB ID: RCSB021668). 1SFM was used for
      docking with GST inhibitors by Hex4.2 macromolecular docking using spherical
      polar Fourier correlations.

PMID- 15864675
TI  - Institutional arrangements and efficiency of health care delivery systems.
AB  - This study examined the efficiency of health care delivery systems in 24 OECD
      countries. Practicing physicians, practicing nurses, inpatient beds, and
      pharmaceuticals were considered as inputs to treat populations of various age
      groups. Data envelopment analysis (DEA) was utilized to calculate efficiency. We
      also calculated input efficiency that should be helpful in determining excess
      number of physicians, nurses, inpatient beds, and pharmaceuticals consumed.
      Institutional arrangements affect efficiency: public-contract and public
      integrated countries are more efficient than public-reimbursement countries.
      Countries in which physicians are paid in wages and salaries and countries with
      capitation have higher efficiency than fee-for-service countries. Countries in
      which a primary care physician acts as a gatekeeper are also more efficient than
      countries without gatekeepers.

PMID- 15864677
TI  - Does long-term ischemia affect the oxidant status during fracture healing?
AB  - INTRODUCTION: The influence of transient circulatory arrest on oxidant status
      during the healing of a tibial fracture was investigated in rats by the use of a
      hindlimb tourniquet technique. MATERIALS AND METHODS: One of the most reliable
      indicators for cytological damage is lipid peroxidation, which can be
      demonstrated by malondialdehyde (MDA) levels. Fifty-eight Wistar rats were used
      in this study. To determine the basal MDA levels of bone, 10 rats not exposed to
      ischemia were killed by an overdose of ether. The remaining 48 rats were randomly
      divided into two groups (control and ischemia). The control and ischemia groups
      were then randomly divided into 4 groups of 6 rats each. In 48 rats, the left
      tibia was fractured and fixed intramedullarly. In the ischemic group, complete
      acute transient ischemia for 4.5 h was imposed after the fracture. In the control
      group, no other intervention except the fracture was done. Rats from the control
      and ischemic groups were killed on days 3, 7, 14, and 28, and MDA levels were
      determined in tibial bone and callus tissue. The MDA levels of the control and
      ischemic groups were compared with basal MDA levels in the bone of 10 rats.
      RESULTS: There was an apparent difference between the basal and control group MDA
      levels on days 3 and 7 (p < 0.01), between the basal and ischemic group MDA
      levels on days 3, 7, and 14 (p < 0.01). In addition, the ischemic group showed a
      statistically significant increase in MDA levels on days 3, 7 and 14 compared
      with the control group (p < 0.01). CONCLUSION: We conclude that complete acute
      transient ischemia affects the oxidant status during fracture healing. This
      effect especially occurs during the ischemic period, inflammation, and callus
      formation of fracture healing.

PMID- 15864678
TI  - A case of trigger finger following partial laceration of flexor digitorum
      superficialis and review of the literature.
AB  - Trigger finger is a common condition, and the usual cause is stenosing
      tenosynovitis. Trigger finger caused by trauma is extremely rare. We examined a
      patient in whom an apparently trivial laceration caused partial laceration of the
      flexor tendon, leading to trigger finger. In this case, ultrasonography was
      useful in establishing the presurgical diagnosis. Removal of the impinging tag
      cured the trigger finger. We also review nine previously reported cases. When
      triggering occurs after an injury near the base of a finger, partial laceration
      of the flexor tendon should be kept in mind as the cause. Ultrasonography may be
      valuable for the diagnosis.

PMID- 15864679
TI  - Therapy with gentamicin-PMMA beads, gentamicin-collagen sponge, and cefazolin for
      experimental osteomyelitis due to Staphylococcus aureus in rats.
AB  - INTRODUCTION: In spite of new surgical techniques and recently developed
      antibiotics, there is no satisfactory solution for the treatment of chronic
      posttraumatic osteomyelitis. The introduction of local antibiotic treatment with
      gentamicin-PMMA beads according to Klemm has provided new stimuli for the
      treatment of chronic osteomyelitis. With the development of collagen as an
      absorbable carrier substance, the disadvantages of the rigid carrier system
      became evident. Due to the varying surgical techniques and different forms of
      adjuvant therapy, it is difficult to assess therapeutic methods and compare
      different studies. Therefore, it seemed appropriate to study the effect of local
      treatment with different antibiotic carriers in the setting of an animal study.
      MATERIALS AND METHODS: The proven rat model for Staphylococcus aureus-induced
      osteomyelitis was used to compare the results of monotherapy with cefazolin,
      gentamicin-PMMA beads, or gentamicin-containing collagen sponge with the
      combination of local and systemic antibiotic treatment. RESULTS: Single-agent
      therapy with parenterally administered cefazolin reduced the CFU from 3.7 x 10(6)
      to 2.9 x 10(4) g(-1) of tibial bone. The effect on osteomyelitis was more
      pronounced with the local application of antibiotics. The best results were
      achieved with the gentamicin-containing collagen sponge which reduced the
      bacterial colony count to 1.4 x 10(2) CFU/g compared with 9.8 x 10(2) CFU/g
      achieved with gentamicin-PMMA beads. The effect was most marked using a 4-week
      combination therapy with local application of the gentamicin-containing collagen
      sponge and systemic administration of cefazolin. In 9 of 11 animals, no bacteria
      could be detected in the bone. CONCLUSION: Each of the treatment modalities
      resulted in a significant therapeutic effect. Due to its ability to quickly
      release large amounts of gentamicin, the flexible gentamicin-containing collagen
      sponge proved to be superior to the rigid PMMA system. Although the gentamicin
      containing collagen sponge provided high antibiotic concentration at the site of
      implantation, an additive effect was attained when combined with systemic
      antibiotic treatment.

PMID- 15864680
TI  - Interspecies transmission of Enterozytozoon bieneusi supported by observations in
      laboratory animals and phylogeny.
AB  - Enterocytozoon bieneusi is emerging as an important cause of chronic diarrhoea in
      AIDS patients. Its reservoirs and transmission patterns are unknown. In this
      study, we have examined E. bieneusi sequences from four Rhesus macaques of
      different origin, which were kept at one animal facility. The sequences were
      identical in all animals, which suggested that infection had occurred within the
      facility. Full sequence agreement of E. bieneusi from macaques was found with an
      E. bieneusi genotype that occurs frequently in humans. To clarify, the relevance
      of possible inter-species transmission from man to macaque, a phylogenetic
      analysis was conducted including all sequences of E. bieneusi deposited in
      GenBank. The hitherto used system of diverse nomenclatures could be reduced to an
      outlier group and three main lineages, one of which could be further sub-divided
      into five subgroups. Based in this phylogeny, an association of parasites and
      host species could be observed for main lineages 2 and 3, as well as for most of
      the subgroups of main lineage 1. For confirmation, the phylogeny of main lineage
      1 was reconstructed with an alternative method of distance estimation, yielding
      essentially the same parasite-host associations. Zoonotic potential of E.
      bieneusi is thus supported on a phylogenetic basis.

PMID- 15864684
TI  - Hyponatremic encephalopathy caused by desmopressin-induced hyponatremia.

PMID- 15864681
TI  - The dissipative contribution of myosin II in the cytoskeleton dynamics of
      myoblasts.
AB  - We have determined the microrheological response of the actin meshwork for
      individual cells. We applied oscillating forces with an optical tweezer to a
      micrometric bead specifically bound to the actin meshwork of C2 myoblasts, and
      measured the amplitude and phase shift of the induced cell deformation. For a non
      perturbed single cell, we have shown that the elastic and loss moduli G' and G''
      behave as power laws f (alpha) and f (beta) of the frequency f (0.01<f <50 Hz),
      alpha and beta being in the range 0.15-0.35. This demonstrates that the
      dissipation mechanisms in a single cell involve a broad and continuous
      distribution of relaxation times. After adding blebbistatin, an inhibitor of
      myosin II activity, the exponent of G' decreases to about 0.10, and G'' becomes
      roughly constant for 0.01<f<10 Hz. The actin meshwork appears less rigid and less
      dissipative than in the control experiment. This is consistent with an inhibition
      of ATPase and reduction of the gliding mobility of myosin II on actin filaments.
      In this frequency range, the actomyosin activity appears as an essential
      mechanism allowing the cell to adapt to an external mechanical stress.

PMID- 15864685
TI  - Immune thrombocytopenic purpura associated with rheumatoid arthritis: case
      report.
AB  - A 54-year-old Japanese woman was diagnosed with rheumatoid arthritis (RA) in 1995
      on the basis of symmetric effusive polyarthritis, morning stiffness, and strongly
      positive rheumatoid factor. She had received low-dose prednisolone, indomethacin,
      methotrexate (MTX), and cyclophosphamide (CPA), at least, over 4 years before the
      current admission and showed partial improvement of polyarthralgia. In November
      2002, she suddenly developed thrombocytopenia (platelet count was 0.3 x 10(4) mm(
      3)) with purpura and was diagnosed with immune thrombocytopenic purpura (ITP). As
      she had refractory ITP, the administration of pulsed high-dose dexamethasone
      (DEX) therapy was started, resulting in the complete remission of ITP. The
      present paper reports that pulsed high-dose DEX therapy was useful for the
      treatment of refractory ITP associated with RA.

PMID- 15864686
TI  - Seronegative spondyloarthropathies in Greece: a population-based study of
      prevalence, clinical pattern, and management. The ESORDIG study.
AB  - The objective of this study was to determine the prevalence, clinical pattern,
      and management of seronegative spondyloarthropathies (SpA) in the general adult
      population of Greece. This population-based study was conducted on a target adult
      (> or =19-year-old) population of 14,233 subjects by rheumatologists who visited
      households in nine dispersed areas. An interview (standardized questionnaire) was
      conducted, clinical evaluation and laboratory investigation were done, and
      established diagnostic classification criteria were used. The age-adjusted and
      sex-adjusted prevalence (prevalence(asa)) of SpA was 0.49% [95% confidence
      interval (CI): 0.38-0.60], with a male to female ratio of 5.5:1; the prevalence
      increased with age until the 59- to 68-year-old age group and declined
      thereafter. The prevalence(asa) of ankylosing spondylitis (AS) and psoriatic
      arthritis (PsA) was 0.24% (95% CI: 0.16-0.32) and 0.17% (95% CI: 0.10-0.24),
      respectively. The mean age (years) at onset was younger in AS (25.83 +/- 6.5)
      than in PsA (45.24 +/- 12.94) (p < 0.01). Familial clustering was noticed in 5.3%
      of AS probands. Sacroiliitis was observed in 39.8% and asymmetrical
      oligoarthritis in 40.6% of PsA patients. Fifty-nine percent of SpA patients had
      previously visited rheumatologists (91.3% diagnosed correctly vs 11.6% of those
      who visited other specialists, p < 0.0005); 56.5% of the former had taken disease
      modifying antirheumatic drugs compared to none of the latter. The SpA in Greeks
      are as common as in other European Caucasians, with a high male preponderance.
      The PsA onset occurs at an older age than AS and frequently presents with a
      spondylitic pattern. The correct diagnosis was arrived at and appropriate
      treatment was given when patients consulted rheumatologists.

PMID- 15864687
TI  - Eosinophilic fasciitis successfully treated with cyclosporine.
AB  - We report on a 45-year-old female who developed eosinophilic fasciitis,
      characterized by scleroderma-like skin indurations, predominantly on the
      extremities and chest, with joint contractures and intermittent blood
      eosinophilia. Histologic examination revealed fibrosis of muscle fascia and
      eosinophilic infiltration. High-dose systemic corticosteroid therapy was
      ineffective, but cyclosporine treatment led to remission.

PMID- 15864688
TI  - Behcet's disease in Poland.

PMID- 15864689
TI  - Optical coherence tomography of the Ex-PRESS miniature glaucoma implant.
AB  - PURPOSE: To describe the localisation of the Ex-PRESS miniature glaucoma implant
      with an experimental setup for optical coherence tomography (OCT) of the anterior
      segment of the eye. METHODS: An OCT scanner, central wavelength 1,280 nm,
      bandwidth 60 nm, resolution of 12 microm, was built onto a slitlamp to scan the
      anterior segment of the eye. Five ex-vivo porcine eyes received an Ex-PRESS
      miniature glaucoma implant and were used as a model to visualise the position of
      the implant in the anterior segment. RESULTS: In the ex-vivo porcine eyes, the
      OCT images showed the anatomy of the anterior segment in great detail. The
      anterior segment OCT was able to visualise the whole outline and position of the
      implant. The abrupt change in reflectivity going from tissue to the implant
      resulted in a clear border along the circumference of the whole device.
      CONCLUSION: In this paper, we have shown that we were able to outline the Ex
      PRESS miniature glaucoma implant in the anterior segment of the ex-vivo porcine
      eye by using an experimental OCT setup built onto a slitlamp. The acquisition
      time of 0.8 s is short enough to allow for the scanning of patients, and anterior
      segment OCT is expected to aid in providing answers to the question regarding
      which parameters will determine the success or failure of such a device.

PMID- 15864691
TI  - Surgical treatment of brain metastasis.
AB  - Treatment modalities for brain metastasis or metastatic brain tumor include
      surgery, conventional irradiation, stereotactic radiosurgery (SRS), chemotherapy,
      and supportive care with corticosteroid. In most cases, these treatments are used
      in combination. For a single metastasis, surgery followed by whole-brain
      radiation therapy (WBRT) has been the standard treatment. SRS has become
      increasingly popular and challenges the standard procedure, but there are still
      insufficient data for the outcomes of combinations including SRS. For the
      treatment of multiple metastases, WBRT is the standard procedure. For tumors
      larger than 3 cm, and in life-threatening situations such as a large metastasis
      to the cerebellum, surgery is the only feasible approach. Histological
      examination is sometimes useful for characterizing metastatic tumors from unknown
      primary sites. Thus, although brain metastasis invariably indicates a stage 4
      cancer, some patients can benefit from surgery.

PMID- 15864692
TI  - Surgical treatment for metastatic malignancies. Pulmonary metastasis: indications
      and outcomes.
AB  - Surgical resection is an important modality in the treatment of pulmonary
      metastases from various solid tumors. The criteria for pulmonary metastasectomy
      are as follows: (1) the patient must be a good risk for surgical intervention;
      (2) the primary malignancy is controlled; (3) there is no other, extrapulmonary,
      metastasis; and (4) the pulmonary lesions are thought to be completely
      resectable. The appropriate selection of candidates according to these criteria
      leads to an overall 5-year survival after pulmonary metastasectomy of about 30%
      40%. However, most of the reported results are retrospective analyses, and the
      significance of pulmonary metastasectomy seems to vary according to the primary
      malignancy. To clarify the significance of surgical treatment for pulmonary
      metastases, we need further analysis of various prognostic factors, with special
      reference to each primary malignancy, as well as a multiinstitutional study, and
      randomized prospective studies, if possible.

PMID- 15864693
TI  - Surgical treatment for metastatic malignancies. Anatomical resection of liver
      metastasis: indications and outcomes.
AB  - Hepatectomy may be the only treatment modality for the cure of colorectal liver
      metastasis. However, whether to perform nonanatomical resection or anatomical
      resection remains unclear. Original articles in English on liver metastasis,
      including reports that dealt with case series of more than 50 curative
      hepatectomies, were reviewed, and the current status of surgical treatment for
      colorectal liver metastasis was summarized, with a special emphasis on the
      relevance, indications, and outcomes of anatomical hepatectomy. Anatomical
      hepatic resection was performed in 63% of the patients. For patients who were
      treated by curative hepatectomy, including both anatomical and nonanatomical
      resection, the morbidity rates, mortality rates, 5-year survival rates, and rates
      of hepatic recurrence were 23%, 3.3%, 34%, and 41.2%, respectively. In 73
      articles that each analyzed more than 50 patients treated with potentially
      curative hepatectomy, the incidence of anatomical resection exceeded 50% in 56
      series, while anatomical resection was performed in fewer than 50% of the
      patients in 17 series. A comparison between these two groups naturally revealed a
      remarkable difference in the incidence of anatomical resection (72% versus 34%),
      but no difference in terms of morbidity; mortality; survival rates at 3, 5, and
      10 years; or rate of hepatic recurrence. The profile of liver metastasis related
      to prognosis was generally advantageous to patients treated with nonanatomical
      resection, and this may have nullified the survival advantage of anatomical
      hepatectomy over nonanatomical resection. Anatomical resection provides a higher
      probability of coresecting microscopic invasions that are predictable but
      undetectable, and can be recommended as a standard procedure for locally advanced
      metastatic liver cancer.

PMID- 15864695
TI  - Surgical treatment of bone metastasis: indications and outcomes.
AB  - Due to advances in cancer treatment that prolong survival, there has been a
      noticeable increase in the prevalence of bone metastasis. Consequently, the
      likelihood of orthopedic surgeons encountering such tumors and the need for
      effective surgical treatment are also expanding. Although bone metastasis
      constitutes only one possible type of metastatic lesion, and while local control
      at a bone metastatic site alone may have little effect on total curability, the
      quality of life (QOL) of the patient cannot be ensured if local control is
      ignored. Therefore, it is important to achieve local control through
      multidisciplinary treatments aimed at both reduced surgery and at conservation of
      limb function. Surgical treatment may be indicated after a series of more
      conservative treatments. Among the main indications are pathologic fracture or a
      high risk of fracture of limb bones. Acute spinal cord injury caused by acute
      compression fracture from spinal metastasis is a relative indication. The
      occurrence of a solitary metastasis, for which extended survival may be
      anticipated, is also an indication for surgery to achieve local control.
      Appropriate local control is required to realize a predicted survival period. As
      well, the surgical method, resection margin, and supplementary treatments, and
      immediately effective reconstruction method should be selected accordingly.

PMID- 15864694
TI  - Surgical treatment for metastatic malignancies. Nonanatomical resection of liver
      metastasis: indications and outcomes.

PMID- 15864696
TI  - Mammary ductoscopy: past, present, and future.
AB  - Mammary ductoscopy (MD) allows direct visual access to the mammary ducts, using
      fiberoptic microendoscopes inserted through the ductal opening onto the nipple
      surface. Therefore it has a potential role in the diagnosis and treatment of
      intraductal breast disease. This article describes the anatomy of the mammary
      ductal system, the early beginnings of MD, its ongoing evolution, and the need
      for further development for its future usage in increasing clinical indications.
      MD is a useful diagnostic adjunct in patients with pathological nipple discharge
      (PND) and can guide duct excision surgery. However, its potential use in the
      early detection of breast cancer, in guiding breast-conserving surgery (BCS) for
      cancer, and in the therapeutic ablation of intraductal disease, as well as in
      guiding risk-reducing strategies among high-risk women, requires further research
      and evaluation. The development of a biopsy kit that obtains adequate microbiopsy
      samples for histological diagnosis under direct visualization will enhance the
      use of this technique by breast surgeons and radiologists. Future developments
      also include combining MD with molecular diagnostic markers and optical biopsy
      systems for the diagnosis of premalignant and early malignant disease, and
      combining MD with radiofrequency for curative ablation of intraductal lesions.

PMID- 15864697
TI  - Transperineal ultrasound-guided 12-core systematic biopsy of the prostate for
      patients with a prostate-specific antigen level of 2.5-20 ng/ml in Japan.
AB  - BACKGROUND: The aim of this study was to investigate the cancer detection rate in
      patients with a prostate-specific antigen (PSA) level of 2.5 to 20 ng/ml, using
      transperineal ultrasound-guided systematic biopsy of the prostate. METHODS: Three
      hundred consecutive patients with PSA levels of 2.5 to 20 ng/ml underwent
      transperineal ultrasound-guided 12-core systematic biopsy of the prostate.
      RESULTS: Prostate cancer was detected in 108 of the 300 patients (36.0%). The
      cancer detection rates in patients with total PSA levels of 2.5-4.0, 4.01-10.0
      and 10.01-20.0 ng/ml were 18.2%, 31.0%, and 50.0%, respectively. The cancer
      detection rates in patients with prostate volumes of less than 30 cc and over 50
      cc were almost 50%, and 13.3%, respectively. The cancer detection rate in
      patients with a PSA density (PSAD) of less than 0.10 ng/ml per cc was only 5.6%,
      and no prostate cancer was detected in patients with a free-to-total PSA ratio (%
      f PSA) over 40%. CONCLUSION: We demonstrated a high prostate cancer detection
      rate by the transperineal ultrasound-guided 12-core systematic biopsy method in
      patients with PSA levels of 2.5 to 20 ng/ml. Accordingly, if the number of core
      biopsies is further increased overall, except in patients with a large prostate
      volume, and if the indication for biopsy is decided based on the PSAD and %f PSA,
      then the cancer detection rate by the present method may be further improved,
      with fewer unnecessary biopsies.

PMID- 15864698
TI  - Intracellular signaling in the induction of apoptosis in a human breast cancer
      cell line by water extract of Mekabu.
AB  - BACKGROUND: We previously reported that water extract of Mekabu, a kind of
      seaweed, induced apoptosis in a human breast cancer cell line. In the present
      study we investigated intracellular signaling in apoptosis, with a focus on
      caspases. METHODS: Mekabu extract, obtained with ultrapure water, was used to
      induce apoptosis in a human breast cancer cell line, MDA-MB231, and DNA
      fractionation was investigated by flow cytometry and electrophoresis. In
      addition, using the caspase detection kit Caspa Tag, activation of caspases 3, 6,
      8, and 9 was observed under a fluorescence microscope. Furthermore, using
      antibodies to caspases 3, 8, 9, and Bid, we conducted a protein analysis by
      Western blotting to determine the activation of these substances. RESULTS:
      Obvious ladder formation demonstrating DNA fractionation was seen, confirming
      that Mekabu extract induced apoptosis. In the fluorescence microscope
      observations, activation of caspases 3, 6, and 8, but not caspase 9, was seen.
      Activated caspases 3 and 8 were detected in the Western blotting analysis, but no
      proteins of activated caspase 9 or Bid were detected. CONCLUSION: Mekabu extract
      activates caspases 3, 6, and 8 and contributes to intracellular signaling to
      induce apoptosis in a human breast cancer cell line. This signaling is not via
      the mitochondria.

PMID- 15864699
TI  - Surgical treatment of malignant tumors of the foot and ankle.
AB  - BACKGROUND: The current study highlights the clinical features of tumors of the
      foot and ankle, and presents the clinical outcomes of treatment for 16 patients
      who were treated at the authors' institution, between 1989 and 1998. METHODS:
      Four tumors occurred in the ankle, three were in the hindfoot, three were in the
      midfoot, three were in the forefoot, and three were on the plantar surface of the
      foot. The median duration of symptoms before presentation was 12 months (range, 1
      50 months). Fourteen patients were managed by limb-salvage procedures. Three
      patients were managed by ablative surgery, due to skin, neurovascular, and/or
      severe bone invasion. In the 9 patients who had wide local resections, local
      island flaps, split-thickness skin grafts, free vascularized latissimus dorsi
      flaps, and a free vascularized iliac crest flap were utilized to achieve wound
      closure. RESULTS: The patients were followed up for a mean of 74.2 months (range,
      48-121 months). The overall survival of the whole group is 71 +/- 3.7 months.
      Currently, 12 patients are being followed up with no evidence of disease. Of the
      14 patients who were managed by limb-salvage procedures, 6 have normal functional
      status. CONCLUSION: Wide resection of malignant tumors of the foot and ankle is
      considered technically difficult because of technical problems of soft-tissue
      coverage. However, utilization of local and free flaps provides sufficient
      closure following wide tumor resection of the foot and ankle, thus yielding
      satisfactory lower extremity function and local tumor control.

PMID- 15864700
TI  - The current status of perioperative chemotherapy for invasive bladder cancer: a
      multiinstitutional retrospective study in Japan.
AB  - BACKGROUND: We conducted a multiinstitutional analysis to clarify the clinical
      significance of perioperative chemotherapy, in invasive bladder cancers in Japan,
      and to identify the patient subpopulations who could benefit from perioperative
      chemotherapy. METHODS: A total of 913 consecutive patients aged less than 80
      years who underwent radical cystectomy for invasive bladder cancer from 1990 to
      2000 at 32 Japanese hospitals were retrospectively analyzed. Median follow-up was
      3.8 years (range, 0.1 to 11.8 years). RESULTS: In total, 341 patients (37.3%)
      were treated with perioperative chemotherapy, including neoadjuvant chemotherapy
      (n = 174), adjuvant chemotherapy (n = 114), or a combination of both
      chemotherapies (n = 53). With cisplatin-based combination chemotherapy, the MVAC
      (methotrexate, vinblastine, doxorubicin, and cisplatin) regimen was the one most
      frequently used for perioperative chemotherapy, but the average number of cycles
      was distinctly less than that in reported randomized trials. MEC (methotrexate,
      epirubicin, and cisplatin) chemotherapy had efficacy similar to that of the MVAC
      regimen. On analysis of patients stratified by stage, the overall survival of
      patients with adjuvant chemotherapy was significantly better than that of those
      without adjuvant chemotherapy, in patients with pT2b, pN0 or pT3, pN0 (P = 0.016
      or 0.020, respectively), but adjuvant chemotherapy had no, or the opposite,
      effect on patients with pT2a, pN0, pT4, pN0, or pTany, pN+. On the other hand,
      neoadjuvant chemotherapy provided a statistically significant survival benefit
      only for patients with clinical T3N0 (P = 0.015). Of note, in the high-risk
      subgroup, the overall survival rate for patients with complete response (CR)
      after neoadjuvant chemotherapy was significantly better than that of patients
      with partial response (PR) or no change (NC)/progressive disease (PD) (P =
      0.043). CONCLUSION: In Japan, cisplatin-based combination chemotherapy has been
      the main modality adopted perioperatively for high-risk patients with radical
      cystectomy. This study's clinical results indicated that perioperative
      chemotherapy may improve survival in patients with T3N0 or pT2b/pT3, pN0 bladder
      cancer.

PMID- 15864701
TI  - Advanced chemoresistant breast cancer responding to multidisciplinary treatment
      with hyperthermia, radiotherapy, and intraarterial infusion.
AB  - We employed multidisciplinary therapy, consisting of hyperthermia, radiotherapy,
      and intraarterial infusion, for a patient with progressive advanced breast cancer
      that was resistant to epirubicin hydrochloride and cyclophosphamide (EC) therapy
      as well as being resistant to docetaxel hydrate, and obtained a good therapeutic
      response. Because estrogen and progesterone receptors were both negative and HER2
      was 3(+), administration of trastuzumab was started, and this patient has shown
      no signs of recurrence at 33 months after our treatment. The results suggested
      that our multidisciplinary therapy can be an effective method for the treatment
      of progressive breast cancer showing resistance to major chemotherapy agents such
      as anthracyclines and taxanes.

PMID- 15864702
TI  - Paraneoplastic hypercalcemia with adenosquamous carcinoma of the colon.
AB  - Hypercalcemia is a well-known manifestation of paraneoplastic syndromes
      associated with a variety of malignancies. However, colon cancer has only rarely
      been associated with hypercalcemia. Here we present the first case of
      adenosquamous carcinoma of the sigmoid colon in a patient who was found to have
      hypercalcemia associated with parathyroid hormone-related protein (PTHrP), with
      no radiological evidence of metastasis to other organs. A 78-year-old woman was
      admitted to our hospital complaining of lower abdominal pain. Physical
      examination and computed tomography revealed a tumor, 13 cm in diameter, in the
      sigmoid colon. Laboratory data showed an elevated serum calcium level (11.2
      mg/dl). Primary colostomy was performed. After the primary operation, the patient
      was found to have hypercalcemia and an elevated PTHrP level. We performed
      sigmoidectomy, total hysterectomy, and partial urinary bladder resection 1 month
      after the primary operation, and both PTHrP and calcium levels immediately
      returned to normal. The histopathologic diagnosis was poorly differentiated
      adenosquamous carcinoma. The patient died due to tumor recurrence 4 months after
      the second surgery.

PMID- 15864703
TI  - Stage IVa squamous cell carcinoma of the vulva managed with primary
      chemoradiation.
AB  - We present the case of a 53-year-old woman with International Federation of
      Gynecology and Obstetrics stage IVa (T3N2M0) squamous cell carcinoma of the
      vulva. Because the urethra was surrounded by a vulvar tumor, she was managed with
      primary chemoradiation in an attempt to spare the morbidity associated with
      exenterative vulvar surgery. Treatment was given as a planned split course,
      consisting of two separate courses of 23.8 Gy each. During each split course of
      radiation, 5-fluorouracil, 1000 mg/m2 per day, was given over the first 4 days,
      and cisplatin 50 mg/m2 was administered as a single infusion on the first day.
      During the 4 days of chemotherapy infusion, the radiation was administered in two
      daily fractions of 1.7 Gy each, given at least 6 h apart. There was no treatment
      break due to adverse effect, and a pathological complete response was achieved in
      the primary tumor and the lymph nodes. The patient did not undergo surgical
      intervention, and has had no evidence of recurrence for 24 months. Chemoradiation
      therapy should be considered as an option in patients with locally advanced
      vulvar cancer to avert the need for exenterative surgery, and to preserve sexual,
      gastrointestinal, and urinary function.

PMID- 15864704
TI  - [Radiofrequency ablation of malignant lung tumours. Judicious approach?].
AB  - BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive technique and
      well established in the treatment of malignant hepatic tumours. This method could
      also find application in patients with malignant lung tumours who, for functional
      reasons, have to be excluded from standard surgery. Until now, however, very
      little data have been available on the application of RFA in malignant pulmonary
      tumours. PATIENTS AND METHODS: From November 2001 to January 2004, eleven
      malignant lesions of the lung were treated with RFA. The indication for RFA
      resulted from an inadequate pulmonary reserve and additional severe risk factors.
      RESULTS: Eleven lesions were treated in ten patients with RFA. The malignancies
      were primary non-small cell bronchial carcinomas (n=9) as well as metastases of
      non-small cell carcinomas (n=2). Early complications of RFA were pneumothorax,
      hemorrhagic intrapleural effusion, bronchopleural fistula and pericarditis. Two
      weeks after RFA, pneumonia appeared as a late complication. No patient's death
      was related to the RFA procedure. After a mean follow-up of 8.5 months five
      patients died. Five patients are still alive, two of whom exhibit no tumour
      recurrence. CONCLUSION: RFA in patients with lung tumours is possible from a
      technical viewpoint. It is possibly a therapeutic alternative for patients with
      localized tumours that are inoperable. However, in this series, the morbidity of
      the procedure -- taking the degree of invasiveness into account -- is high, and
      the oncological results are unsatisfactory, possibly due to a small cohort of
      patients.

PMID- 15864705
TI  - Successful treatment of multiple Pseudallescheria boydii brain abscesses and
      ventriculitis/ependymitis in a 2-year-old child after a near-drowning episode.
AB  - RATIONALE: We report on a cerebral infection by Pseudallescheria boydii in a 21
      month-old boy after a near-drowning episode. MRI revealed multiple (> 60)
      intracerebral abscesses. METHODS: The surgical therapy included CSF drainage and
      microsurgical resection of one abscess for microbiological diagnosis. Antimycotic
      therapy included terbinafine and intraventricular caspofungin in addition to
      voriconazole. RESULTS: Systemic side effects of chemotherapy were not observed.
      After placement of a ventriculoperitoneal shunt, the boy was transferred to a
      rehabilitation clinic and improved neurologically. After 20 months, MRI
      documented a continuing remission of the disease. CONCLUSION: Our case proves
      that an aggressive treatment should be undertaken and can be successful in CNS
      pseudallescheriasis.

PMID- 15864706
TI  - Congenital gemistocytic astrocytoma in a fetus.
AB  - INTRODUCTION: Congenital brain tumors, especially tumors diagnosed before birth,
      are very rare. This report presents a case of a congenital gemistocytic
      astrocytoma diagnosed by antenatal intrauterine ultrasound. CASE REPORT: An
      intrauterine MRI revealed hydrocephalus and a mass lesion including massive
      hemorrhage in the right occipital lobe of a fetus. The patient was delivered by
      cesarean section and a total excision of the hemorrhagic tumor was carried out on
      the third day of his life. The histological study revealed gemistocytic
      astrocytoma (WHO grade II). Neither adjuvant chemotherapy nor radiation was given
      after the first surgery. Ten months after his birth, a recurrent tumor was
      depicted on follow-up MRI. The second total excision of the recurrent tumor and
      chemotherapy using cisplatin and vincristine were performed. OUTCOME: The patient
      is free of disease at the age of 2 years and 6 months.

PMID- 15864708
TI  - Strategies for gastric cancer treatment in the twenty-first century: minimally
      invasive and tailored approaches integrating basic science and clinical medicine.

PMID- 15864707
TI  - A case of moyamoya disease presenting with chorea.
AB  - CASE REPORT: We describe a 15-year-old girl with moyamoya disease whose initial
      manifestation was chorea-like involuntary movements. T2-weighted magnetic
      resonance imaging showed high signal intensity lesions in the left frontal lobe,
      right parieto-occipital lobes, and frontal subcortical white matter. Single
      photon emission computed tomography (SPECT) showed diffuse hypoperfusion of the
      whole brain. Bilateral direct and indirect cerebrovascular bypass surgeries were
      performed. Chorea disappeared 2 days after the surgery. Follow-up SPECT
      demonstrated increased cerebral perfusion in the bilateral frontal, temporal, and
      parietal regions. CONCLUSIONS: Chorea accompanied with moyamoya disease can be
      properly managed by revascularization surgery. Moyamoya disease should be
      remembered as being one of the differential diagnoses of chorea, which is
      treatable by surgery.

PMID- 15864709
TI  - Gastric cancer: the dispute between East and West.

PMID- 15864710
TI  - Thirty-four-year experience of immunochemosurgery for gastric cancer in 14,033
      cases.

PMID- 15864711
TI  - Current status of surgery for gastric cancer: a review.
AB  - In the last three decades, considerable progress has been made in the diagnosis
      and management of gastric cancer. This was initiated by the Japanese and taken up
      by other focus groups in Asia, the United States, and Europe. Exciting prospects
      have been identified with the molecular characterization of the mutated gene
      causative for familial gastric cancer, and new developments in endoscopy and
      laparoscopy for diagnosis, management, and treatment continue. It is now clear
      that the extent of the gastric resection requires only that an R0 resection be
      performed and that total gastrectomy is not necessary for all patients with
      gastric adenocarcinoma. The extent of nodal dissection is defined as a major
      factor in staging and can influence outcome by stage. The recent development of
      defining adequate staging based on at least 15 nodes being sampled is a clear
      example of a simple system that can make major differences in overall management.
      The role of extended node dissection has been studied in prospective randomized
      trials showing no overall survival benefit but perhaps benefit to selected
      subgroups. The importance of the hospital and surgical experience in improving
      mortality and long-term survival is established. The role of adjuvant therapy,
      both pre- and postoperative, continues to be evaluated with some frustration that
      a single trial, as yet unconfirmed by subsequent trials, is considered the
      "standard of care" in the United States. The international gastric cancer
      community can help define the important issues that need to be answered in the
      coming decades.

PMID- 15864712
TI  - The history of gastric cancer: legends and chronicles.

PMID- 15864713
TI  - Laparoscopic surgery for gastric cancer: preliminary experience.
AB  - BACKGROUND: Laparoscopic surgery for gastric cancer (GC) was introduced in the
      past decade because it was considered less invasive than open surgery, resulting
      in less postoperative pain, faster recovery, and improved quality of life.
      Several studies have demonstrated the safety and feasibility of this procedure.
      We analyzed our preliminary experience with this procedure. METHODS: From
      November 2003 to December 2004, 20 patients affected by gastric adenocarcinoma
      were operated on with a totally laparoscopic or laparoscopic-assisted approach.
      This series included 10 women and 10 men, aged from 34 to 75 years. Procedures
      consisted of eight total gastrectomies, three subtotal Billroth I and seven
      Billroth II gastrectomies, one proximal gastrectomy, and one wedge resection.
      According to the TNM classification, we observed five patients at stage Ia, four
      at stage Ib, three at stage II, one at stage IIIa, two at stage IIIb, and five at
      stage IV. RESULTS: In all patients the procedures were completed without any
      conversion. Operative time ranged from 150 to 300 min. The number of dissected
      lymph nodes ranged from 23 to 47. No mortality was observed. Overall morbidity
      rate was 10% (two cases), with one enteric fistula and one esophagojejunal
      anastomotic leakage associated with pancreatitis. Excluding these two patients,
      postoperative stay was between 12 and 20 days. CONCLUSIONS: Even though
      accompanied by a difficult learning curve, safety and feasibility are widely
      demonstrated, but a skilled and experienced surgeon is required. Accurate
      selection of patients is mandatory and curative resection is achievable in cases
      where GC is not advanced.

PMID- 15864714
TI  - Recent advances in multimodal treatment for gastric cancer: a review.
AB  - The prognosis after surgical treatment of gastric cancer remains poor. This
      review aims to clarify the indication for multimodal treatment of gastric cancer.
      A systematic literature research and evaluation of clinical data presented at
      important international cancer meetings were undertaken. Recently published
      results of large randomized phase III trials underscore the potential value of
      neoadjuvant chemotherapy or adjuvant chemoradiotherapy in gastric cancer.
      However, data from randomized controlled trials are still scarce, and it remains
      uncertain which subgroups of patients should routinely undergo multimodal
      treatment. In view of the side effects of pre- and foremost postoperative
      therapies, a more distinct definition of prognostic and predictive markers is
      warranted. Neoadjuvant chemotherapy is a rising option in locally advanced
      gastric cancer. Adjuvant chemoradiation has been shown to be beneficial in
      gastric cancer patients who have undergone suboptimal surgical resection. The
      benefits of adjuvant chemotherapy alone seem to be very small.

PMID- 15864715
TI  - Molecular-pathological prognostic factors of gastric cancer: a review.
AB  - Invasion and metastasis are critical determinants of cancer morbidity. Genes and
      molecules participating in these steps must be regarded as potential prognostic
      factors. Growth factors and their receptors, cell-cycle regulators, cell-adhesion
      molecules and matrix-degrading enzymes are those to be used as prognostic
      factors, including epidermal growth factor (EGF), EGF receptor, K-sam, HER-2,
      interleukin (IL)-8, vascular endothelial growth factor (VEGF), cyclin E, p27, E
      cadherin, CD44v6, matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of
      matrix metalloproteinase-1 (TIMP-1). Alterations in epigenetics, such as aberrant
      DNA methylation and histone modification that are, in part, associated with the
      tumor progression of gastric cancer, can be candidate prognostic factors. The
      number of methylated genes may serve as a marker of tumor progression. Genetic
      polymorphism not only affects cancer susceptibility but also influences malignant
      phenotype; examples include single-nucleotide polymorphism in the HER-2 and MMP-9
      genes. Comprehensive gene expression analyses are useful to search for novel
      genes related to invasion and metastasis and potential prognostic factors. Serial
      analysis of gene expression (SAGE) has identified several these genes, such as
      CDH17, APOE, FUS, COL1A1, COL1A2, GW112, and MIA. Overexpression of MIA is found
      to be associated with poor prognosis. Microarray analysis has great potential for
      identifying the characteristics of individual cancers, from the view point of
      gene expression profiles. A combination of these examinations can not only
      foretell a patient's prognosis but can also give information directly connected
      with personalized cancer medicine and prevention.

PMID- 15864716
TI  - Current status and future prospects of chemotherapy for metastatic gastric
      cancer: a review.
AB  - Although many randomized trials of chemotherapy for metastatic gastric cancer
      have been reported during the past two decades, no standard regimens worldwide
      have been established yet. Reference arms vary depending on the region and
      cultural differences. To date, a combination of 5-fluorouracil (5-FU) and
      cisplatin is most widely used. However, no confirmation of survival advantage
      over single-agent 5-FU in a randomized trial has been proved yet, and there
      remain limitations of efficacy results in older-generation regimens. Recently
      developed new agents such as irinotecan, taxanes (paclitaxel and docetaxel), and
      new oral fluorouracil (S-1 and capecitabine) provided more promising results: a
      response rate over 50% and median survival time (MST) over 10 months in their
      preliminary combination studies. These newer combination regimens are now being
      investigated in various randomized phase III studies, which will clarify whether
      the newer-generation regimens provide survival advantage over older-generation
      regimens. The MST of the new standard should exceed 11 months to be considered a
      definite improvement, and overall survival seems to be a more desirable primary
      end point than progression-free survival in a randomized trial. Molecular
      targeting agents are another concern to improve the treatment outcomes of this
      disease and are now under investigation in combination with conventional
      cytotoxic agents. Both clinical and biological research will be more important in
      future studies.

PMID- 15864717
TI  - Minimally invasive surgery for gastric cancer--toward a confluence of two major
      streams: a review.
AB  - The minimalization of therapeutic invasiveness in order to preserve quality of
      life (QOL) is a major topic in the management of early gastric cancer. After
      laparoscopic surgery for gastric cancer was introduced by Kitano et al. in 1991,
      an enthusiasm to develop laparoscopic procedures has grown steadily. In the
      initial phase, early gastric cancer limited to the mucosal layer with no risk of
      lymph node metastasis was treated by laparoscopic wedge resection or intragastric
      mucosal resection. Since technical and instrumental advances in endoscopic
      treatment were achieved by gastroenterologists, these cases can be managed by
      intraluminal endoscopic approaches. The attention of surgeons then shifted to
      more radical procedures such as laparoscopic gastrectomy with lymph node
      dissection, which is comparable to open surgery and can be indicated even in
      advanced cancer. Although this paradigm shift has already been realized in the
      field of colorectal surgery, we must pay attention to the particular biological
      nature of gastric cancer in terms of the potential of peritoneal dissemination.
      While early-phase recovery after surgery has been improved by laparoscopic
      surgery, preservation of late-phase QOL by function-preserving surgery is also
      essential in this regard; therefore, the sentinel node (SN) concept has been a
      much-discussed topic in gastric cancer surgery to approach this aspect. Recently,
      the validity of the SN concept has been demonstrated by a number of single
      institutional studies, and prospective multicenter trials are currently ongoing.
      Theoretically, various types of function-preserving surgery could be applied in
      cases of early gastric cancer with negative SNs as less invasive surgery to
      improve long-term QOL. Although we still have to solve several remaining issues
      in the treatment of gastric cancers, a confluence of these two major streams,
      laparoscopic surgery and sentinel node navigation surgery, would enable us to
      apply a novel individualized minimally invasive approach, both in terms of degree
      of incisional access and extent of function preservation.

PMID- 15864718
TI  - Long-term outcome of S-1 and cisplatin combination therapy in patients with
      advanced or recurrent gastric cancer.
AB  - BACKGROUND: Although combination therapy of S-1 and cisplatin (CDDP) has
      excellent efficacy against gastric cancer, the effect of the treatment on
      survival has been unclear. The aim of this study was to evaluate the long-term
      outcome of this combination therapy. METHODS: Sixty-three patients with advanced
      or recurrent gastric cancer were treated with S-1, with or without CDDP, as first
      line chemotherapy, and the clinical results were compared retrospectively. S-1
      was administered orally at a standard dose of 80 mg/m(2). In the treatment of the
      S-1 group, S-1 was given for 28 consecutive days, followed by a 14-day rest. In
      the treatment of the S-1/CDDP group, S-1 was given for 21 consecutive days,
      followed by a 14-day rest, and CDDP, at 60 mg/m(2), was infused on day 8.
      RESULTS: The incidence of adverse reactions of more than grade 3 was 22.5% in the
      S-1 group and 43.5% in the S-1/CDDP group, and the treatment compliance was
      better in the S-1 group. The overall response rate was 25.9% in the S-1 group,
      and 36.8% in the S-1/CDDP group. The combination of S-1 with CDDP had better
      effects on the primary lesion and on differentiated-type carcinoma than S-1
      alone. However, there was no difference in survival between the two patient
      groups. The median survival time after the initiation of treatment in the S-1
      group was 322 days, and that in the S-1/CDDP group was 319 days. CONCLUSIONS: Our
      results suggest that the combination of CDDP with S-1 does not improve the long
      term outcome of S-1 therapy.

PMID- 15864719
TI  - Gastric adenocarcinoma among Hmong in California, USA, 1988-2000.
AB  - BACKGROUND: This study examined gastric adenocarcinoma incidence, mortality, and
      tumor characteristics in the Hmong population of California, 1988-2000. Many
      Hmong relocated to the United States at the conclusion of the Vietnam War.
      Resettlement difficulties encountered by Hmong have included socioeconomic and
      healthcare issues. Hmong are wary of Western medicine and would resort to it as
      the last option, which may delay the diagnosis and treatment of diseases such as
      cancer. METHODS: Data from the California Cancer Registry were used to calculate
      incidence and mortality rates for Hmong, and were compared to these in Asian
      Pacific Islanders (API) and non-Hispanic whites (NHW). The population at risk was
      estimated through linear interpolation, using data from the 1990 and 2000
      decennial censuses. RESULTS: Hmong experienced incidence and mortality rates of
      gastric adenocarcinoma several times higher than those of API and NHW. More than
      97% of Hmong patients chose no treatment, compared to only 25.6% of API and 30.3%
      of NHW patients. Hmong were more likely to be diagnosed with cancer at later
      stages but at better histologic grades than API and NHW. CONCLUSIONS: Further
      investigations into Helicobacter pylori, Epstein-Barr virus, acid reflux, and
      dietary practices of Hmong living in the United States are needed before any firm
      conclusion can be made, as these risk factors may impact gastric cancer
      development. Hmong should also be encouraged to use traditional and Western
      medicines simultaneously, provided that traditional healthcare practices do not
      interfere with biomedicines.

PMID- 15864720
TI  - Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer:
      role of IL-6 as a prognostic factor.
AB  - BACKGROUND: It is becoming clear that various cytokines are associated with the
      spread of cancer cells. The purpose of this study was to compare interleukin (IL)
      6 levels in patients with gastric cancer to elucidate the role of IL-6 in
      predicting the spread of tumors. METHODS: In 60 patients, we assessed the
      correlation of serum IL-6 (pg/ml) with stage, histological findings, hepatic
      metastasis, and related factors (hepatocyte growth factor [HGF], IL-1beta, tumor
      necrosis factor [TNF]-alpha, and transforming growth factor [TGF]-beta1). We also
      investigated the diagnostic significance of the IL-6 level for advanced gastric
      cancer and lymph node metastasis, as well as the association between IL-6
      elevation and outcome. Finally, we examined the expression of IL-6 in tumor
      tissue. RESULTS: Significant relationships were seen between serum IL-6 and
      stage, depth of tumor invasion (pT), lymphatic invasion (ly), venons invasion
      (v)*, lymph node metastasis (pN), hepatic metastasis (cH), and HGF (P < 0.01; *P
      < 0.05). With regard to the diagnostic significance of the IL-6 level for
      advanced gastric cancer and lymph node metastasis, when the cutoff value of IL-6
      was set at 1.97 pg/ml, the sensitivity was 81.8% and 87.5%; specificity was 66.7%
      and 58.3%; and accuracy was 77.1% and 72.9%, respectively. The 1- and 3-year
      cumulative survival rates for patients with an IL-6 value of more than 1.97 pg/ml
      (69.0% and 43.4%, respectively) were significantly lower than those for patients
      with an IL-6 value of 1.97 pg/ml or less (94.4% and 87.2%, respectively; P <
      0.05). Immunohistochemical staining was positive for IL-6 in the cytoplasm of
      cancer cells. CONCLUSION: We suspect that IL-6 is involved in cancer invasion and
      lymph node and/or hepatic metastasis. Our results indicate that IL-6 could be
      used as a prognostic factor for survival.

PMID- 15864721
TI  - Synthesis of modular dipeptide mimetics on the basis of diazabicycloalkanes and
      derivatives thereof with sulphur containing side chains.
AB  - We present the synthesis of new modular dipeptide mimetics based on
      diazabicycloalkane backbones. These diazabicycloalkanes are ligands for the
      prostate specific membrane antigen (PSMA), a well known tumor marker. Our
      previously described synthetic route to enantiomerically pure diazabicycloalkanes
      is extended to yield polyfunctional diazabicycloalkanes with a modular character
      using a new ring closing methodology. This, finally, allows us to attach linker
      moieties to different positions of the diazabicycloalkane scaffold providing
      conjugation sites to other functional molecules such as markers or cytostatic
      compounds. Furthermore, successful synthesis of sulphur-containing dipeptide
      analogues as for example CysX(AA)- or HCysX(AA)-mimetics on the basis of
      diazabicycloalkanes is described.

PMID- 15864722
TI  - The antioxidant effect of beta-Glucan on oxidative stress status in experimental
      spinal cord injury in rats.
AB  - This study was performed to investigate the antioxidant effect of beta-Glucan in
      experimental spinal cord injury (SCI). Injury was produced using weight-drop
      technique in rats. beta-Glucan was given by intraperitoneal injection following
      trauma. The rats were sacrificed at the sixth day of injury. Oxidative stress
      status was assessed by measuring the spinal cord tissue content of
      Malonyldialdehyde (MDA), Superoxide Dismutase (SOD) and Gluthatione Peroxidase
      (GSH-Px) activities. No effect of beta-Glucan on SOD and MDA activities was found
      but, GSH-Px levels were found to decrease to the baseline (preinjury) levels when
      it was compared to untreated group (U=0.000; p=0.002). According to our results,
      beta-Glucan works like a scavenger and has an antioxidant effect on lipid
      peroxidation in spinal cord injury.

PMID- 15864723
TI  - Statistical theory of force-induced unzipping of DNA.
AB  - The unzipping transition under the influence of external force of a dsDNA
      molecule has been studied using the Peyrard-Bishop Hamiltonian. The critical
      force F(c)(T) for unzipping calculated in the constant force ensemble is found to
      depend on the potential parameter k which measures the stiffness associated with
      a single strand of DNA and on D, the well depth of the on-site potential
      representing the strength of hydrogen bonds in a base pair. The dependence on
      temperature of F(c)(T) is found to be (T(D) - T)(1/2) (T(D) being the thermal
      denaturation temperature) with F(c)(T(D)) = 0 and F(c)(0) = [Formula: see text].
      We used the constant extension ensemble to calculate the average force F(y)
      required to stretch a base pair a y distance apart. The value of F(y) needed to
      stretch a base pair located far away from the ends of a dsDNA molecule is found
      twice the value of the force needed to stretch a base pair located at one of the
      ends to the same distance for y >/= 1.0 A. The force F(y) in both cases is found
      to have a very large value for y approximately 0.2 A compared to the critical
      force found from the constant force ensemble to which F(y) approaches for large
      values of y. It is shown that the value of F(y) at the peak depends on the value
      of krho which measures the energy barrier associated with the reduction in DNA
      strand rigidity as one passes from dsDNA to ssDNA and on the value of the depth
      of the on-site potential. The effect of defects on the position and height of the
      peak in the F(y) curve is investigated by replacing some of the base pairs
      including the one being stretched by defect base pairs. The formation and
      behaviour of a loop of Y shape when one of the ends base pair is stretched and a
      bubble of ssDNA with the shape of "an eye" when a base pair far from ends is
      stretched are investigated.

PMID- 15864724
TI  - Anisotropic elastic properties of microtubules.
AB  - We review and model the experimental parameters which characterize elastic
      properties of microtubules. Three macroscopic estimates are made of the
      anisotropic elastic moduli, accounting for the molecular forces between tubulin
      dimers: for a longitudinal compression of a microtubule, for a lateral force and
      for a shearing force. These estimates reflect the anisotropies in these
      parameters observed in several recent experiments.

PMID- 15864725
TI  - Periodic saddle-splay Freedericksz transition in nematic liquid crystals.
AB  - By use of a local stability criterion recently introduced, we predict the
      existence of a periodic saddle-splay Freedericksz (PSSF) transition that adds to
      the existing class of classical Freedericksz transitions driven in a nematic cell
      by an external field. Occurrence of the PSSF transition requires a saddle-splay
      elastic constant with a large enough magnitude and different anchoring strengths
      at the plates confining the nematic cell. Otherwise, either the PSSF transition
      does not occur at all, or it requires a field higher than that associated with
      the classical aperiodic splay Freedericksz (ASF) transition, in which case it is
      not observable. Here, we determine the threshold field for which the PSSF
      precedes the ASF transition, as well as the structure of the destabilizing mode.

PMID- 15864726
TI  - Viscoelastic response of diblock copolymers to oscillatory shear.
AB  - A mesoscopic model for diblock copolymers is combined with a simple rheological
      description of the viscoelastic contrast of its two phases. Under oscillatory
      shear the contrast generates secondary velocity fields and substantial deviations
      of volume-averaged flow parameters. The validity of our analytical findings is
      tested with three-dimensional numerical simulations. Furthermore, we consider the
      effect of advection by the generated flows on the stability of ordered lamellar
      states and propose a new criterion for the selection of orientations.

PMID- 15864727
TI  - Undulation versus Frederiks instability in nematic elastomers in an external
      electric field.
AB  - We study the behaviour of a nematic side-chain elastomer under the influence of
      an external static electric field for a specific geometry. For this
      investigation, the nematic elastomer is considered to be a perfect insulator. On
      the basis of a macroscopic description we generalize the classical Frederiks
      transition in a low-molecular-weight (LMW) nematic liquid crystal to the
      elastomeric case. We predict, using a linear stability analysis, that the onset
      of the instability can be qualitatively different from the LMW case: in liquid
      crystalline elastomers an undulation instability can arise at onset. Whether the
      analogue of a Frederiks instability or an undulation instability occurs first
      depends on the sample thickness as well as on the material parameters. It turns
      out that the parameter which describes the coupling between the deformations of
      the elastomer and the relative rotations between the elastomer and the director
      field of the nematic phase is most important for the predicted response of the
      system. Furthermore, we find that the magnitude of the critical electric field is
      much higher in the elastomeric than in the low-molecular-weight case.

PMID- 15864728
TI  - An enhanced polarization mechanism for the metal cations modified amorphous TiO2
      based electrorheological materials.
AB  - In the present work, we developed a new kind of electrorheological (ER)
      materials, metal cations modified amorphous TiO(2) gels. The static yield stress
      of Sn(4+) modified amorphous TiO(2) gel based ER fluid with a volume fraction Phi
      = 38% reaches 26.2 kPa at E = 3.5 kV/mm. The result shows that metal cations can
      significantly enhance the ER activity of amorphous TiO(2) gels. We then proposed
      a novel ER effect mechanism (metal cations enhanced polarization mechanism) to
      clarify the experimental results. We believe that it is the metal cations that
      enhanced the polarization of the polar groups (-OH) which results in the
      corresponding enhancement of the interfacial polarization.

PMID- 15864729
TI  - Effects of the rate of evaporation and film thickness on nonuniform drying of
      film-forming concentrated colloidal suspensions.
AB  - In this paper, we report on nonuniform distribution of film-forming waterborne
      colloidal suspensions above the critical concentration phi(c) of the colloidal
      glass transition during drying. We found that colloidal suspension films dry
      nonuniformly when the initial rate of evaporation E and/or the initial thickness
      l(0) are high. We found that a Peclet number Pe, defined as Pe = El(0)/D, where D
      is the diffusion coefficient of the colloids in the diluted suspensions, does not
      predict uniformity of drying of the concentrated suspensions, contrary to the
      reported work on drying of diluted suspensions. Since the colloidal particles are
      crowded and their diffusive motion is restricted in concentrated suspensions, we
      assumed that above phi(c) water is transported to the drying surface by
      hydrodynamic flow along the osmotic pressure gradient. The permeability of water
      through channels between deforming particles is estimated by adapting the theory
      of foam drainage. We defined a new Peclet number Pe' by substituting the
      transport coefficient of flow (defined as the permeability divided by the
      viscosity, multiplied by the osmotic pressure gradient) for the diffusion
      coefficient. This extended Peclet number predicted the nonuniform drying with a
      criterion of Pe' > 1. These results indicate that the mechanism of water
      transport to the drying surface in concentrated suspensions is water permeation
      by osmotic pressure, which is faster than mutual diffusion between water and
      particles --that has been observed in diluted suspensions and discussed by Routh
      and Russel. The theory fits well the experimental drying curves for various
      thicknesses and rates of evaporation. The particle distribution in the drying
      films is also estimated and it is indicated that the latex distribution is
      nonuniform when Pe' > 1.

PMID- 15864730
TI  - Stability limit of a granular monolayer.
AB  - A granular monolayer is composed by spherical grains on a horizontal plate. The
      plate is then tilted until the monolayer breaks down. This critical angle has
      been measured for different widths and heights of the rectangular monolayer. The
      highest critical angles are found when one of these two characteristic lengths is
      less than about 30 bead diameters. When the polydispersity is less than one
      percent, the monolayer may be stable till angles close to 90( degrees ). Arches
      induce large critical angles. On the other hand, for a large and high monolayer,
      the critical angle saturates towards a lower value. This angle is related to the
      static friction of a grain on the plate. A model based on the block dynamics is
      proposed to describe the behavior of the avalanche angle as a function of the
      size of the monolayer and the polydispersity of the beads.

PMID- 15864731
TI  - Pearling instabilities in water-dispersed copolymer cylinders with charged
      brushes.
AB  - We investigate the structural behavior of a poly(styrene)-block-poly(acrylic
      acid) diblock copolymer which forms hexagonally-packed PS cylinders (C-phase) in
      the melt state. The water dispersion of this structure provides hairy cylinders
      which comprise a PAA swollen cylindrical brush with a height h tunable via its
      degree of ionization and the ionic strength in the solution, and a water-free, PS
      cylindrical core of constant radius R(C). Such system constitutes an "out-of
      equilibrium" frustrated model system: the selective swelling of the PAA brush
      results in a frustration of the interface curvature, which the ratio h/R(C)
      allows to quantify. Upon heating at a temperature higher than the glass
      transition temperature of the PS core, the glassiness of the core is relieved and
      the mechanical constraints arising from the selective swelling of the structure
      can be relaxed: the cylinders undergo a cylinder-to-sphere transition upon
      annealing at high temperature, when above a frustration threshold h/R(C)
      approximately 1.8. Thanks to a careful mapping of the transition diagram, an
      undulating cylindrical morphology (UC) is identified between unchanged cylinders
      ( h/R(C) approximately 1.8) and spheres ( h/R(C) < or = 2.0), which appears to
      result from a Rayleigh-like pearling instability of the copolymer cylinders.

PMID- 15864732
TI  - From the stress response function (back) to the sand pile "dip".
AB  - We relate the pressure "dip" observed at the bottom of a sand pile prepared by
      successive avalanches to the stress profile obtained on sheared granular layers
      in response to a localized vertical overload. We show that, within a simple
      anisotropic elastic analysis, the skewness and the tilt of the response profile
      caused by shearing provide a qualitative agreement with the sand pile dip effect.
      We conclude that the texture anisotropy produced by the avalanches is in essence
      similar to that induced by a simple shearing --albeit tilted by the angle of
      repose of the pile. This work also shows that this response function technique
      could be very well adapted to probe the texture of static granular packing.

PMID- 15864733
TI  - Fracture and friction: Stick-slip motion.
AB  - We discuss the stick-slip motion of an elastic block sliding along a rigid
      substrate. We argue that for a given external shear stress this system shows a
      discontinuous nonequilibrium transition from a uniform stick state to uniform
      sliding at some critical stress which is nothing but the Griffith threshold for
      crack propagation. An inhomogeneous mode of sliding occurs when the driving
      velocity is prescribed instead of the external stress. A transition to
      homogeneous sliding occurs at a critical velocity, which is related to the
      critical stress. We solve the elastic problem for a steady-state motion of a
      periodic stick-slip pattern and derive equations of motion for the tip and
      resticking end of the slip pulses. In the slip regions we use the linear friction
      law and do not assume any intrinsic instabilities even at small sliding
      velocities. We find that, as in many other pattern forming system, the steady
      state analysis itself does not select uniquely all the internal parameters of the
      pattern, especially the primary wavelength. Using some plausible analogy to first
      order phase transitions we discuss a "soft" selection mechanism. This allows to
      estimate internal parameters such as crack velocities, primary wavelength and
      relative fraction of the slip phase as functions of the driving velocity. The
      relevance of our results to recent experiments is discussed.

PMID- 15864735
TI  - Human T-cell leukemia virus type I: 25 years of progress and challenges.

PMID- 15864736
TI  - Galectin-1 receptors in different cell types.
AB  - Galectins are a family of animal lectins defined by two properties: shared amino
      acid sequences in their carbohydrate-recognizing domain, and beta-galactoside
      affinity. A wide variety of biological phenomena are related to galectins, i.e.,
      development, differentiation, morphogenesis, tumor metastasis, apoptosis, RNA
      splicing, and immunoregulatory function. In this review, we will focus on
      galectin-1 receptors, and some of the mechanisms by which this lectin affects
      different cell types. Several galectin-1 receptors are discussed such as CD45,
      CD7, CD43, CD2, CD3, CD4, CD107, CEA, actin, extracellular matrix proteins such
      as laminin and fibronectin, glycosaminoglycans, integrins, a beta-lactosamine
      glycolipid, GM1 ganglioside, polypeptide HBGp82, glycoprotein 90 K/MAC-2BP, CA125
      cancer antigen, and pre-B cell receptor.

PMID- 15864737
TI  - Mycoplasma-mediated alterations of in vitro generation and functions of human
      dendritic cells.
AB  - While tumor cell-derived factors have been demonstrated to hamper the in vitro
      differentiation and maturation of dendritic cells (DCs) from hematopoietic stem
      cells, their effects on DC differentiation from CD14+ plastic-adherent monocytic
      precursors have been controversial. To address this issue, we examined the
      effects of the culture supernatants from six tumor cell lines on in vitro DC
      differentiation and maturation from monocytes. Two tumor cell supernatants,
      MDA468 and 293T, were found to be able to affect the in vitro differentiation of
      DCs from monocytic precursors, leading to the generation of a distinct type of DC
      with markedly reduced expression of DC-SIGN, downregulation of CD11c, HLA-DR and
      CD1a, and upregulation of CD123, HLA-ABC, CD80, CD40, CD86, CD54, CD83, CD25 and
      CCR7. Functionally, these DCs exhibited reduced phagocytosis and enhanced
      allostimulatory capacity. Further investigation demonstrated that the changes in
      DC phenotype and functions were due to the presence of mycoplasmas in these two
      cell lines; eradication of mycoplasmas completely abolished the observed effects,
      and importantly, pure mycoplasmas in the absence of tumor cell supernatants were
      able to produce the same effects. Since mycoplasmas are common contamination
      agents in routine tissue culture, our results caution that many reported effects
      of DCs in culture warrant re-evaluation. The distinct effects of mycoplasmas on
      DC differentiation described in this report could potentially benefit future
      development of DC-based vaccination and therapeutic applications.

PMID- 15864738
TI  - T cell responses to allogeneic human mesenchymal stem cells: immunogenicity,
      tolerance, and suppression.
AB  - Human mesenchymal stem cells (MSCs) were evaluated for their ability to activate
      allogeneic T cells in cell mixing experiments. Phenotypic characterization of
      MSCs by flow cytometry showed expression of MHC Class I alloantigens, but minimal
      expression of Class II alloantigens and costimulatory molecules, including CD80
      (B7-1), CD86 (B7-2), and CD40. T cells purified from peripheral blood mononuclear
      cells (PBMCs) did not proliferate to allogeneic MSCs. Lack of response was not
      due to a deficiency of costimulation, since retroviral transduction of MSCs with
      either B7-1 or B7-2 costimulatory molecules did not result in
      lymphoproliferation. Although these results suggested that MSCs were
      immunologically inert or potentially tolerogenic, T cells cultured with MSCs
      produced IFN-gamma and displayed secondary kinetics to restimulation with PBMCs,
      indicating alloantigen priming rather than tolerance induction by the MSCs. To
      determine whether MSCs suppressed alloreactive T cells, MSCs were added to
      primary mixed lymphocyte reaction (MLR) cultures. MSCs suppressed cell
      proliferation when added at the initiation of culture or when added to an ongoing
      MLR culture. Suppression was dose-dependent, genetically unrestricted, and
      occurred whether or not MSCs were pretreated with IFN-gamma. MSCs in transwell
      chambers suppressed primary MLR cultures, indicating that suppression was
      mediated by soluble molecules. Analysis of cytokines in suppressed MLR cultures
      demonstrated up-regulation of IFN-gamma and IL-10, and down-regulation of TNF
      alpha production relative to control cultures. We conclude that MSCs can initiate
      activation of alloreactive T cells, but do not elicit T cell proliferative
      responses due to active suppressive mechanisms.

PMID- 15864739
TI  - Development of immunoglobulin G enzyme-linked immunosorbent assay for the
      serodiagnosis of severe acute respiratory syndrome.
AB  - Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused
      by a novel SARS-associated coronavirus (SARS-CoV). The clinical characteristics
      are high fever, rapidly progressive diffuse pneumonitis and respiratory distress.
      It is highly infectious through intimate contact or direct contact with
      infectious body fluids. Outbreaks within communities and hospitals have been
      reported. Development of rapid and reliable diagnostic tools is urgently needed.
      We developed an immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA),
      using whole virus antigen of SARS-CoV. Eighty-six serum samples collected from
      patients who were hospitalized for other causes were examined to determine the
      cut-off O.D. value. The cut-off O.D. value was defined as 0.175 by calculating
      the mean O.D. value of the 86 sera plus 3 standard deviations. To determine the
      sensitivity and specificity of the ELISA, 56 positive sera and 204 negative sera
      were tested. The sensitivity was 96.4% and the specificity was 100%. The results
      suggest that the IgG ELISA using whole virus antigen of SARS-CoV has a high
      sensitivity and specificity in detecting SARS IgG antibodies. This IgG ELISA is a
      powerful tool for serodiagnosis of SARS.

PMID- 15864740
TI  - Down-regulation of the polymeric immunoglobulin receptor in non-small cell lung
      carcinoma: correlation with dysregulated expression of the transcription factors
      USF and AP2.
AB  - The polymeric immunoglobulin receptor (PIGR) mediates transport of IgA and IgM
      antibodies across mucosal and glandular epithelia. Several studies have utilized
      immunohistochemistry to demonstrate that PIGR expression varies in different
      types of lung carcinoma, and is down-regulated during tumor progression. We have
      previously shown in cultured tumor cell-lines that basal transcription of the
      PIGR gene is regulated by the transcription factors USF1, USF2 and AP2. To
      examine the mechanism by which PIGR expression is down-regulated in lung
      carcinoma, RNA was microdissected from formalin-fixed, paraffin-embedded lung
      carcinomas (14 adenocarcinomas and 8 squamous cell carcinomas). Levels of PIGR,
      USF1, USF2 and AP2-alpha mRNA were quantified by real-time reverse transcriptase
      polymerase chain reaction and normalized to mRNA for the housekeeping gene GAPDH.
      PIGR mRNA levels were decreased in adenocarcinomas and squamous cell carcinomas
      relative to adjacent non-tumor tissue, and were inversely correlated with stage
      of differentiation. USF1 and USF2 mRNA levels were reduced in adenocarcinomas
      relative to non-tumor tissue, while AP2-alpha levels were elevated. Multivariate
      regression analysis demonstrated that reduced USF2 mRNA and increased AP2-alpha
      mRNA levels were predictive of down-regulated PIGR mRNA expression in the
      majority of adenocarcinomas and in moderately differentiated squamous cell
      carcinomas.

PMID- 15864741
TI  - The distinct effects of a butanol fraction of Bidens pilosa plant extract on the
      development of Th1-mediated diabetes and Th2-mediated airway inflammation in
      mice.
AB  - Bidens pilosa is claimed to be useful for immune or anti-inflammatory disorders;
      however, little scientific evidence has been published concerning its function.
      In this paper, immune disease mouse models were used to study the function of a
      butanol fraction of B.pilosa. We demonstrated treatment with the butanol fraction
      of B.pilosa ameliorated Th1 cell-mediated autoimmune diabetes in nonobese
      diabetic (NOD) mice but caused deterioration of Th2 cell-mediated airway
      inflammation induced by ovalbumin (OVA) in BALB/c mice. We next showed that Th2
      cytokines (IL-4 and/or IL-5) increased but Th1 cytokine (IFN-gamma) decreased
      following injections with the butanol fraction of B.pilosa in both mouse strains.
      Accordingly, Th2 cytokine-regulated IgE production in mouse serum increased
      following treatment with this fraction. Finally, we found that the butanol
      fraction of B.pilosa inhibited Th1 cell differentiation but promoted Th2 cell
      differentiation. Taken together, the butanol fraction of B.pilosa has a
      dichotomous effect on helper T cell-mediated immune disorders, plausibly via
      modulation of T cell differentiation.

PMID- 15864742
TI  - ICAM-1 induction by TNFalpha and IL-6 is mediated by distinct pathways via Rac in
      endothelial cells.
AB  - Atherogenesis is a chronic inflammatory response and intercellular adhesion
      molecule (ICAM-1) induced by cytokines plays a role in this event. In this study,
      the molecular mechanisms of tumor neurosis factor alpha (TNFalpha)- and IL-6
      induced ICAM-1 gene expression in endothelial cells (ECs) were examined. ECs
      infected with adenovirus carrying the dominant negative mutant of Rac (Ad-RacN17)
      exhibited inhibition in both TNFalpha- and IL-6-induced ICAM-1 expression.
      Consistently, ECs transfected with RacN17 inhibited both TNFalpha- and IL-6
      induced ICAM-1 promoter activities. Functional analysis of ICAM-1 promoter,
      however, indicated that the cis-acting elements in response to TNFalpha and IL-6
      are different. The NFkappaB binding site in the ICAM-1 promoter region was
      crucial for TNFalpha-induced ICAM-1 expression but not for the induction by IL-6.
      ECs infected with Ad-RacN17 attenuated the TNFalpha-induced NFkappaB binding
      activity. In contrast, IL-6 activated a transcriptional factor, signal transducer
      and activator of transcription-3 (Stat3) via the phosphorylation of Tyr705 at
      Stat3. ECs transfected with the dominant negative mutant of Stat3 (Stat3F)
      demonstrated that Stat3 was required for IL-6-induced ICAM-1 gene expression.
      Interestingly, the phosphorylation of Tyr705 and Ser727 in Stat3 was greatly
      inhibited in IL-6-treated ECs previously infected with Ad-RacN17. Our data
      strongly indicated that ICAM-1 gene induction by TNFalpha and IL-6 is mediated
      mainly via NFkappaB and Stat3, respectively and Rac1 appears to play a central
      role in modulating cytokine-induced ICAM-1 expression in ECs.

PMID- 15864743
TI  - Protein remodeling of the heart ventricles in hereditary hypertriglyceridemic
      rat: effect of ACE-inhibition.
AB  - The aim of this study was to determine whether protein remodeling of the heart
      ventricles and remodeling of the aorta were present in hereditary
      hypertriglyceridemic (hHTG) rats and whether treatment with the angiotensin
      converting enzyme inhibitor, captopril could prevent these alterations. Three
      groups of rats were investigated in a four week experiment control Wistar
      /C/rats, hHTg rats, hHTg rats given captopril (100 mg/kg/day) (hHTg + CAP). In
      the hHTg group, the increased systolic blood pressure (SBP) was associated with
      hypertrophy of the LV and RV. Protein profile analysis revealed an enhancement of
      metabolic protein concentration in both ventricles. The concentration of total
      collagenous proteins was not changed in either ventricles. However, alterations
      in composition of cardiac collagen were detected, characterized by higher
      concentration of hydroxyproline in pepsin-insoluble fraction and lower
      concentration of hydroxyproline in pepsin soluble faction in the LV. Hypertrophy
      of aorta, associated with the reduction of nitric oxide dependent relaxation, was
      also present in hHTG rats. Captopril normalized SBP, reduced left ventricular
      hypertrophy (LVH), diminished metabolic protein concentration in both ventricles,
      and improved NO-dependent relaxation of the aorta. Furthermore, captopril
      partially reversed alterations in hydroxyproline concentration in soluble and
      insoluble collagenous fractions of the LV. We conclude that hypertrophy of both
      ventricles and the aorta are present in hHTG rats, along with protein remodeling
      of both ventricles. Captopril partially prevented left ventricular hypertrophy
      development and protein remodeling of the myocardium.

PMID- 15864744
TI  - Denbinobin-mediated anticancer effect in human K562 leukemia cells: role in
      tubulin polymerization and Bcr-Abl activity.
AB  - Denbinobin (5-hydroxy-3,7-dimethoxy-1,4-phenanthraquinone) has been reported to
      exhibit anti-tumor and anti-inflammatory activity. Nevertheless, the anti-tumor
      mechanism of denbinobin remains unclear. In the present study, we evaluated the
      anticancer activity of denbinobin in human myelogenous K562 leukemia cells. In
      accordance with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide
      (MTT) assay, we demonstrated that denbinobin inhibited cell viability in a
      concentration-dependent manner with an IC50 value of 1.84 microM. Cell cycle
      analysis illustrated that exposure of denbinobin caused a G2/M phase accumulation
      in a time-dependent manner. Tubulin polymerization in cells was apparently
      enhanced by denbinobin, implying that denbinobin might have a regulatory role in
      tubulin/microtubule. Furthermore, denbinobin significantly suppressed the
      expression of Bcr-Abl and phosphorylation of CrkL, a crucial tyrosine kinase and
      an adaptor protein in chronic myeloid leukemia, respectively. Denbinobin also
      markedly enhanced CD11b expression after a long-term treatment, suggesting that
      denbinobin might play a role in facilitating differentiation in K562 cells. In
      summary, we have demonstrated that denbinobin displays anticancer effects in K562
      cells through the increase of levels of tubulin polymerization and deregulation
      of Bcr-Abl signaling. Our data demonstrate that denbinobin could be a potential
      anticancer lead compound for further development.

PMID- 15864745
TI  - Role of mitogen-activated protein kinase pathway in reactive oxygen species
      mediated endothelin-1-induced beta-myosin heavy chain gene expression and
      cardiomyocyte hypertrophy.
AB  - Endothelin-1 (ET-1) has been found to increase cardiac beta-myosin heavy chain
      (beta-MyHC) gene expression and induce hypertrophy in cardiomyocytes. ET-1 has
      been demonstrated to increase intracellular reactive oxygen species (ROS) in
      cardiomyocytes. The exact molecular mechanism by which ROS regulate ET-1-induced
      beta-MyHC gene expression and hypertrophy in cardiomyocytes, however, has not yet
      been fully described. We aim to elucidate the molecular regulatory mechanism of
      ROS on ET-1-induced beta-MyHC gene expression and hypertrophic signaling in
      neonatal rat cardiomyocytes. Following stimulation with ET-1, cultured neonatal
      rat cardiomyocytes were examined for 3H-leucine incorporation and beta-MyHC
      promoter activities. The effects of antioxidant pretreatment on ET-1-induced
      cardiac hypertrophy and mitogen-activated protein kinase (MAPKs) phosphorylation
      were studied to elucidate the redox-sensitive pathway in cardiomyocyte
      hypertrophy and beta-MyHC gene expression. ET-1 increased 3H-leucine
      incorporation and beta-MyHC promoter activities, which were blocked by the
      specific ET(A) receptor antagonist BQ-485. Antioxidants significantly reduced ET
      1-induced 3H-leucine incorporation, beta-MyHC gene promoter activities and MAPK
      (extracellular signal-regulated kinase, p38, and c-Jun NH2 -terminal kinase)
      phosphorylation. Both PD98059 and SB203580 inhibited ET-1-increased 3H-leucine
      incorporation and beta-MyHC promoter activities. Co-transfection of the dominant
      negative mutant of Ras, Raf, and MEK1 decreased the ET-1-induced beta-MyHC
      promoter activities, suggesting that the Ras-Raf-MAPK pathway is required for ET
      1 action. Truncation analysis of the beta-MyHC gene promoter showed that the
      activator protein-2 (AP-2)/specificity protein-1 (SP-1) binding site(s) were(was)
      important cis-element(s) in ET-1-induced beta-MyHC gene expression. Moreover, ET
      1-induced AP-2 and SP-1 binding activities were also inhibited by antioxidant.
      These data demonstrate the involvement of ROS in ET-1-induced hypertrophic
      responses and beta-MyHC expression. ROS mediate ET-1-induced activation of MAPK
      pathways, which culminates in hypertrophic responses and beta-MyHC expression.

PMID- 15864746
TI  - Polyvalent GalNAcalpha1-->Ser/Thr (Tn) and Galbeta1-->3GalNAcalpha1-->Ser/Thr (T
      alpha) as the most potent recognition factors involved in Maclura pomifera
      agglutinin-glycan interactions.
AB  - The agglutinin isolated from the seeds of Maclura pomifera (MPA) recognizes a
      mucin-type disaccharide sequence, Galbeta1-->3GalNAc (T) on a human erythrocyte
      membrane. We have utilized the enzyme-linked lectinosorbent assay (ELLSA) and
      inhibition assay to more systematically analyze the carbohydrate specificity of
      MPA with glyco-recognition factors and mammalian Gal/GalNAc structural units in
      lectin-glycoform interactions. From the results, it is concluded that the high
      densities of polyvalent GalNAcalpha1-->Ser/Thr (Tn) and Galbeta1-->3GalNAcalpha1-
      >Ser/Thr (T(alpha)) glycotopes in macromolecules are the most critical factors
      for MPA binding, being on a nanogram basis 2.0 x 10(5), 4.6 x 10(4) and 3.9 x
      10(4) more active than monovalent Gal, monomeric T and Tn glycotope,
      respectively. Other carbohydrate structural units in mammalian glycoconjugates,
      such as human blood group Sd (a+) related disaccharide (GalNAcbeta1-->4Gal) and
      Pk/P1 active disaccharide (Galalpha1-->4Gal) were inactive. These results
      demonstrate that the configurations of carbon-4 and carbon-2 are essential for
      MPA binding and establish the importance of affinity enhancement by high-density
      polyvalencies of Tn/T glycotopes in MPA-glycan interactions. The overall binding
      profile of MPA can be defined in decreasing order as high density of polyvalent
      Tn/T(alpha) (M.W. > 4.0 x 10(4)) >> Tn-containing glycopeptides (M.W. < 3.0 x
      10(3)) > monomeric T/Tn and P (GalNAcbeta1-->3Gal) > GalNAc > Gal >> Man, L: ARA:
      , D: Fuc and Glc (inactive). Our findings should aid in the selection of this
      lectin for elucidating functions of carbohydrate chains in life processes and for
      applications in the biomedical sciences.

PMID- 15864747
TI  - Further characterization of the binding properties of two monoclonal antibodies
      recognizing human Tn red blood cells.
AB  - The terminal alpha anomeric Ga1NAc residue is an essential sugar for the Tn
      glycotope, human blood group A determinant, and Forssman antigen. In a previous
      study [King M.J., Parson S.F., Wu A,M., Jones N., Transfusion 31: 142-149, 1991]
      we defined two monoclonal antibodies (MoAbs, BRIC66 and BRIC111) reacting with
      human Tn red blood cells. However, more advanced studies of these two MoAbs were
      hampered by the lack of availability of Gal/GalNAc related glycotopes. In order
      to use these antibodies as powerful probes to elucidate structural changes during
      life processes, we have characterized in detail the combining sites of these two
      MoAbs using enzyme-linked immunosorbent (ELISA) and inhibition assays with an
      extended glycan/ligand collection. From the results, it has been established that
      BRIC66 demonstrated multiple specificities and its reactivity towards glycotopes
      was defined as: Ga1NAc alpha1-->Ser/Thr (Tn) > or = Ga1NAc alpha1-->3(LFuc alpha1
      ->2)Gal (Ah) > Ga1NAcalpha1-->3Galbeta1-->4Glc (AL) > Ga1NAalpha1-->3Gal (A)
      GalNAc alpha1-->3GalNAc >> Gal or Glc. Another MoAb, BRIC111, mainly bound Tn
      glycophorin. The best ligand for this MoAb was Tn-containing glycopeptides (M.W.
      < 3.0 x 10(3) Da) from asialo ovine salivary mucin (OSM), which was approximately
      70 and 58 times more active than Ga1NAc and monomeric Ga1NAc alpha1-->Ser/Thr
      (Tn), respectively, suggesting that the active glycotopes present in glycophorin
      for BRIC111 binding also exist in OSM. The N-acetyl group at carbon-2 and
      configuration at carbon-2 and carbon-4 of the alpha anomeric Ga1NAc are required
      for the binding of either MoAb. Identification of these binding properties should
      aid in the selection of these MoAbs and the conditions required for biological
      studies and clinical applications.

PMID- 15864748
TI  - Lectinochemical studies on the glyco-recognition factors of a Tn (GalNAcalpha1-
      >Ser/Thr) specific lectin isolated from the seeds of Salvia sclarea.
AB  - The lectin extracted from the seeds of Salvia sclarea (SSL) recognizes the Tn
      antigen (GalNAc alpha1-->Ser/Thr) expressed in certain human carcinomas. In
      previous studies, knowledge of the binding properties of SSL was restricted to
      GalNAcalpha1--> related oligosaccharides and glycopeptides. Thus, the
      requirements of functional groups in monosaccharide and high-density polyvalent
      carbohydrate structural units for SSL binding and an updated affinity profile
      were further evaluated by enzyme-linked lectinosorbent (ELLSA) and inhibition
      assays. Among the glycoproteins (gps) tested for interaction, a high density of
      exposed Tn-containing glycoproteins such as in the armadillo salivary Tn
      glycoprotein and asialo ovine salivary glycoprotein reacted best with SSL. When
      the gps were tested for inhibition of SSL binding, which was expressed as 50%
      nanogram inhibition, the high density polyvalent Tn present in macromolecules was
      the most potent inhibitor. Among the monosaccharide and carbohydrate structural
      units studied, which were expressed as nanomole inhibition, GalNAc alpha1-
      >3GalNAc beta1-->3Gal alpha1-->4Gal beta1-->4Glc (Fp), GalNAc alpha1-->3Gal beta1
      ->4Glc (A(L)), GalNAc alpha1-->3GalNAc beta1-->Me (F beta), GalNAc alpha1-
      >3GalNAc alpha1-->Me (F alpha) and GalNAc alpha1--> Ser/Thr (Tn) were the most
      active ligands, being 2.5-5.0 x 10(3) and 1.25-2.5 times more active than Gal and
      GalNAc, respectively. From the results, it is suggested that the combining site
      of SSL is a shallow groove type, recognizing the monosaccharide of GalNAc as the
      major binding site or Tn up to the Forssman pentasaccharide (Fp). It can be
      concluded that the three critical factors for SSL binding are the -NH CH(3)CO at
      carbon-2 in Gal, the configuration of carbon-3 in GalNAc, and the polyvalent Tn
      (GalNAc alpha1-->Ser/Thr) present in macromolecules. These results should assist
      in understanding the glyco-recognition factors involved in carbohydrate-lectin
      interactions in biological processes. The effect of the polyvalent F alpha, F
      beta and GalNAc beta1-->3Gal alpha1--> (P alpha) glycotopes on binding should be
      examined. However, this is hampered by the lack of availability of suitable
      reagents.

PMID- 15864749
TI  - Antifibrotic effects of Salvia miltiorrhiza on dimethylnitrosamine-intoxicated
      rats.
AB  - Excessive oxidative stress is implicated in hepatic fibrogenesis. Extracts of
      Salvia miltiorrhiza (Sm) have been shown to protect cells against oxidative
      stress. In this study we investigated the in vitro and in vivo effects of Sm on
      hepatic fibrosis. A cell line of rat hepatic stellate cells (HSC-T6) was
      stimulated with transforming growth factor-beta1 (TGF-beta1). The inhibitory
      effects of Sm (50-400 microg/ml) on TGF-beta1-induced alpha-smooth muscle actin
      (alpha-SMA) secretion and the mRNA expressions of fibrosis-related genes,
      including alpha-SMA, connective tissue growth factor (CTGF), and tissue inhibitor
      of metalloproteinase-1 (TIMP-1), were assessed. Fibrosis was induced by
      dimethylnitrosamine (DMN) administration in rats. DMN-treated rats were randomly
      assigned to 1 of 4 groups: saline, Sm (20 mg/kg), Sm (100 mg/kg), or silymarin
      (100 mg/kg), each given by gavage twice daily for 5 weeks starting from the onset
      of DMN administration. Sm (200 and 400 microg/ml) significantly inhibited TGF
      beta1-stimulated alpha-SMA secretion and the mRNA expressions of alpha-SMA, CTGF,
      and TIMP-1 in HSC-T6 cells. Fibrosis scores of livers from DMN-treated rats with
      either a low (1.8 +/- 0.2) or high (1.8 +/- 0.1) dose of Sm, or silymarin (1.4 +/
      0.2) were significantly reduced in comparison with DMN-treated rats receiving
      saline (3.1 +/- 0.1). Hepatic collagen contents were also significantly reduced
      by either Sm or silymarin treatment. The mRNA expression levels of alpha-SMA, TGF
      beta1, and procollagen I were all attenuated in Sm- and silymarin-treated rats.
      Moreover, levels of plasma aspartate transaminase activities were reduced by Sm
      and silymarin treatment. In conclusion, our results show that Sm exerted
      antifibrotic effects in both HSC-T6 cells and in rats with DMN-induced fibrosis.

PMID- 15864750
TI  - The role of nitric oxide in the spatial heterogeneity of basal microvascular
      blood flow in the rat diaphragm.
AB  - The effects of N omega-nitro-L: -arginine (L: -NOARG) and N(G)-monomethyl-L: 
      arginine (L: -NMMA) on the spatial distribution of diaphragmatic microvascular
      blood flow were assessed in anesthetized, mechanically ventilated rats.
      Microvascular blood flow was measured after different periods at either a fixed
      site (Q stat) or 25 different sites (Q scan) using computer-aided laser-Doppler
      flowmetry (LDF) scanning. The value of Q stat was unaffected after 15-20 min
      superfusion with any one of the following agents: L: -NOARG (0.1 mM), L: -NMMA
      (0.1 mM), L: -arg (10 mM). The cumulative frequency histogram of the Q scan value
      in the control group displayed a non-Gaussian distribution that was not
      significantly affected after 15 min superfusion with the vehicle of L: -NOARG.
      Superfusion with either L: -NMMA or L: -NOARG at 0.1 mM for 15 min displaced the
      histogram of cumulative frequency to the left, with the median value of blood
      flow decreasing by 10 to 20%. However, skewness and kurtosis of the distribution
      of basal Q(scan) were unaffected after superfusion of either of the L: -arg
      analogues. Pretreatment with L: -arg (10 mM), followed by co-administration of L:
      -arg (10 mM) with L: -NOARG (0.1 mM) only partially prevented L: -NOARG from
      exerting this inhibitory effect on the distribution of basal Q scan, while
      pretreatment with L: -arg in the same manner could prevent L: -NMMA from exerting
      its inhibitory effect. There was a weak but significant linear relationship
      between the magnitude of basal Q(scan) and normalized changes in basal Q scan
      after superfusion of either of the L: -arg analogues. In conclusion, a basal NO
      activity is present in the diaphragmatic microvascular bed of rats. LDF scanning
      rather may yield more vivid information about the extent of overall tissue
      perfusion than conventional LDF whenever basal NO activity is involved. Moreover,
      the parallel flow profiles after NO synthase blockade suggest that the spatial
      inhomogeneity of basal diaphragmatic microvascular blood flow is not dependent on
      basal NO formation.

PMID- 15864751
TI  - Diurnal rhythmic expression of the rhythm-related genes, rPeriod1, rPeriod2, and
      rClock, in the rat brain.
AB  - High densities of the mRNA of three rhythm-related genes, rPeriod1 (rPer1),
      rPer2, and rClock, which share high homology in Drosophila and mammals, are found
      in the rat hypothalamic suprachiasmatic nucleus (SCN). The SCN, however, is not
      the only brain region that expresses these genes. To understand the possible
      physiological roles of these rhythm-related genes, we examined expression of
      these genes in different brain regions at various time points in male Sprague-
      Dawley rats. Using semi quantitativein situ hybridization with 35S-riboprobes to
      evaluate mRNA levels, the diurnal rhythmicity of rPer1, and rPer2 mRNA levels was
      found in the SCN, arcuate nucleus, and median eminence/pars tuberalis. Expression
      patterns of mRNA for rPer1 and rPer2, however, were not similar in these brain
      regions. The rhythmicity in these brain regions was specific, because it was not
      observed in the cerebellum or hippocampus. Moreover, diurnal changes in rClock
      mRNA expression were not detected in any of the brain regions examined. These
      findings suggest that the different expression patterns observed for rPer1,
      rPer2, and rClock mRNAs may be attributed to their different physiological roles
      in these brain regions, and support previous work indicating that circadian
      rhythms in the brain are widespread.

PMID- 15864752
TI  - Regulation of a novel cell differentiation-associated gene, JWA during oxidative
      damage in K562 and MCF-7 cells.
AB  - Oxidative stress, or the production of oxygen-centered free radicals, has been
      hypothesized as the major source of DNA damage that can lead to a variety of
      diseases including cancer. It is known that 8-hydroxy-deoxyguanosine (8-oxo-dG)
      is a useful biomarker of oxidative DNA damage. Our recent data showed that JWA,
      initially being cloned as a novel cell differentiation-associated gene, was also
      actively responsive to environmental stressors, such as heat-shock, oxidative
      stress and so on. In the present study, we have applied a modified comet assay
      and bacterial repair endonucleases system (endonuclease III and
      formamidopyrimidine glycosylase) to investigate if JWA is involved in hydrogen
      peroxide (H2O2)-induced DNA damage and repair in K562 and MCF-7 cells, and to
      demonstrate if the damage is associated with 8-oxo-dG. The results from the comet
      assay have shown that the average tail length and the percentage of the cells
      with DNA tails are greatly induced by H2O2 treatment and further significantly
      enhanced by the post-treatment of repair endonucleases. The H2O2-induced 8-oxo-dG
      formation in K562 and MCF-7 cells is dose-dependent. In addition, the data have
      clearly demonstrated that JWA gene expression is actively induced by H2O2
      treatment in K562 and MCF-7 cells. The results suggest that JWA can be regulated
      by oxidative stress and is actively involved in the signal pathways of oxidative
      stress in the cells.

PMID- 15864753
TI  - Cyclooxygenase-2 increases hypoxia-inducible factor-1 and vascular endothelial
      growth factor to promote angiogenesis in gastric carcinoma.
AB  - Cyclooxygenase-2 (COX-2) is an inducible enzyme important in inflammation and
      which is overexpressed in a variety of cancers. This study investigated its role
      in angiogenesis of gastric carcinoma (GC). Immunohistochemical examination of
      surgical specimens showed a positive correlation among COX-2, vascular
      endothelial growth factor (VEGF), and vasculature in GC. After transfection with
      a COX-2-expressing vector, the AGS GC cell line showed increases in both
      proliferation and tube formation of human umbilical vein endothelial cells
      (HUVECs). These in vitro angiogenic effects on HUVECs were reduced either by
      blocking VEGF or NS-398, a COX-2 inhibitor. To elucidate the mechanism by which
      COX-2 increases angiogenesis, we established a COX-2-expressing clone, AGS/COX-2,
      and its vector control clone, AGS/pcDNA3, and verified their functions by
      determining prostaglandin E2 (PGE2). Among 6 angiogenesis-associated factors,
      VEGF was considerably expressed in AGS/COX-2. After reducing hypoxia-inducible
      factor-1alpha (HIF-1alpha) protein by antisense HIF-1alpha transfection, VEGF
      production was reduced in AGS/COX-2 cells in a dose-dependent manner. We found
      that HIF-1alpha increased concomitantly with VEGF after exogenous PGE2
      stimulation to wild-type AGS cells, but this effect was blocked by SC19220, a
      PGE2 receptor antagonist. In addition, pretreatment with NS-398 to reduce PGE2
      also effectively suppressed HIF-1alpha protein accumulation and achieved a
      similar inhibitory effect on VEGF production as did antisense HIF-1alpha
      transfection. Our work supports the COX-2/PGE2/HIF-1alpha/VEGF pathway possibly
      contributing to tumor angiogenesis in GC.

PMID- 15864755
TI  - Phylogenetic analysis of Alysiella and related genera of Neisseriaceae: proposal
      of Alysiella crassa comb. nov., Conchiformibium steedae gen. nov., comb. nov.,
      Conchiformibium kuhniae sp. nov. and Bergeriella denitrificans gen. nov., comb.
      nov.
AB  - A phylogenetic analysis based on 16S rRNA gene sequences reveals that Alysiella
      filiformis belongs to the family Neisseriaceae. The genus Simonsiella is
      phylogenetically separated by the genera Kingella and Neisseria. The species
      Simonsiella crassa and A. filiformis show a close phylogenetic relationship, with
      the 16S rDNA sequence similarity and the DNA-DNA hybridization representing 98.7%
      and 35%, respectively. Therefore, S. crassa should be transferred from the genus
      Simonsiella to the genus Alysiella as Alysiella crassa comb. nov. Simonsiella
      steedae and Simonsiella sp. of cat origin show strong genetic affinities and are
      distantly related with the type species of Simonsiella, S. mulleri. Thus, a new
      genus, Conchiformibium is proposed; Conchiformibium steedae comb. nov. and
      Conchiformibium kuhniae sp. nov. are accommodated in this new genus. On the basis
      of the phylogenetic, phenotypic and chemotaxonomic distinction from the genus
      Neisseria, N. denitrificans should be reclassified, for which a new genus and new
      combination Bergeriella denitrificans are proposed.

PMID- 15864756
TI  - Genetic variations in the pgm locus among natural isolates of Yersinia pestis.
AB  - A PCR-based screening method was used to study the genetic variations of the pgm
      locus among natural isolates of Yersinia pestis from China. Our results indicate
      that genetic variations in the pgm locus are well correlated with biovars of Y.
      pestis and plague foci, suggesting that the pgm locus plays a role in Y. pestis
      adaptation to its environment. The gene encoding two-component regulatory system
      sensor kinase became a pseudogene in all strains of biovar Orientalis due to a
      thymidine deletion, while it is intact in all the strains of the other biovars.
      Only strains from Foci H and L are the same as Yersinia pseudotuberculosis in
      that they have an intact transmembrane helix in the sensor kinase protein, which
      is lost in all the other strains because of the 18 bp in-frame deletion. The
      IS100 element that flanks the 39 terminus of the pgm locus was inserted into the
      chromosome during the within-species microevolution of Y. pestis, which is absent
      in strains from Foci G, H and L and also in Y. pseudotuberculosis. This fact
      indicates that the strains from these three foci are of an older lineage of
      Chinese Y. pestis. It is this IS100 element's absence that maintained high
      stability of the pgm locus in the Y. pestis strains from these three foci. The
      IS285 element insertion in the pigmentation segment and the IS100 element
      insertion in the downstream flanking region of the pgm locus are only present in
      strains from Foci H and L. The flanking region outside the 59 terminus of the
      upstream IS100 element is identical in the strains from these two foci, which is
      different in the other strains. All of these unique characteristics suggest that
      they are of a special lineage of Chinese Y. pestis.

PMID- 15864757
TI  - Carica papaya seed macerate as inhibitor of conjugative R plasmid transfer from
      Salmonella typhimurium to Escherichia coli in vitro and in the digestive tract of
      gnotobiotic mice.
AB  - In this study, the effect of Carica papaya seed macerate on conjugal R plasmid
      transfer from Salmonella typhimurium to Escherichia coli was investigated in
      vitro and in the digestive tract of gnotobiotic mice. Twenty-five micrograms per
      milliliter and 430 mg (administered intragastrically twice a day) of papaya seed
      macerate concentrations were used during conjugation for in vitro and in vivo
      assays, respectively. High frequency of conjugation inhibition by macerate was
      observed for both in vitro and in vivo experiments, independently of bacterial
      growth and mating conditions. Papaya seed macerate caused a reduction of the
      transconjugant population ranging from 71% to about 100%. There was no lethal
      effect of the seed macerate on donor or recipient cells in the concentrations
      used. Once the mechanisms and magnitude of resistance gene transfer are clearly
      understood, strategies to reduce or minimize the dissemination of these genes
      could be relevant. The data here obtained show a clinical potential use of papaya
      seed macerate on this transfer.

PMID- 15864758
TI  - Simultaneous methanogenesis and phototrophic bacterial growth in relatively dry
      sewage sludge under light.
AB  - Anaerobically digested sewage sludge with a variety of moisture content, namely
      81%, 86%, 90% and 98%, were anaerobically cultured at 35 degrees C under light.
      Phototrophic bacteria grew in the 86% moisture sludge (bacteriochlorophyll a,
      0.46 g/L), 90% sludge (bacteriochlorophyll a, 0.36 g/L) and 98% sludge
      (bacteriochlorophyll a, 0.04 g/L) with methane production. Phototrophic bacteria
      could not grow in the 81% moisture sludge (bacteriochlorophyll a 0.004 g/L).
      Phototrophic bacteria could assimilate about 46% of the extracellular ammonium in
      the 90% moisture sludge. Phototrophic bacteria utilized organic compounds
      competing with methanogens; therefore, methane yield from the 90% moisture sludge
      under the light conditions was lower than that under the dark conditions.
      Phototrophic bacteria could grow in anaerobically digested sludge with relatively
      low moisture content, and assimilated extracellular ammonium in the sludge. The
      quality of digested sludge with phototrophic bacterial biomass for fertilizer
      could be improved compared with that without phototrophic bacterial biomass.

PMID- 15864759
TI  - Phylogenetic position of the yeast strain Saccharomycodes sinensis IFO 10111.

PMID- 15864760
TI  - Sporobolomyces fushanensis sp. nov., a new species of ballistoconidium-forming
      yeast in the Microbotryum lineage isolated from a plant in Taiwan.

PMID- 15864761
TI  - Undecanoic acid resistance in filamentous fungi: identification and linkage
      mapping of the Aspergillus nidulans udaA gene.

PMID- 15864762
TI  - Comparison of media performances for the recovery of some yeasts from grape
      juice.

PMID- 15864763
TI  - [Future trends in school health nursing].
AB  - School health nursing is one of the "frontline" professional community nursing
      services. School nurses need both theoretical professional knowledge and
      practical skills. The tasks of school nurses are becoming increasingly important
      due to the changing social environment, changes in disease patterns, decreasing
      birth rates, and the increasing demands of today's customers. But the field of
      school health nursing enjoys a certain independence. In line with society's
      demands, the essential trend in school health nursing is specialization. Planned
      and well-arranged pre-service education is required to develop programs for
      school nurse specialists, and, more importantly, we need to return to the
      advancement system. Nurses working at schools need plenty of clinical, practical
      experience, ideally having completed in-service education at N3 level in a
      medical institution, so that they can bring their professional competence into
      play, and satisfy the demands of their work. In this way, the nurses work in
      medical institutions will still have opportunities to contribute their skills
      when they are elderly. This is a constructive and positive development for the
      nursing profession.

PMID- 15864764
TI  - [Care at school: health care needs and coping strategies among children whose
      mothers are foreign wives].
AB  - Families formed as a result of a marriage involving an immigrant are a new
      phenomenon in Taiwan. School children whose mothers are foreign wives are
      increasing. Because of differences in lifestyle and culture, and because of
      stereotyping, such families are vulnerable and prone to experiencing unequal
      treatment. How will they fare when their children start elementary school? This
      article explores the physical and psychosocial health needs and health care
      utilization of school-aged children whose mothers are foreign wives. It also
      explores factors which might arise in the case of these children because of
      social inequality. The authors emphasize the importance of school health and
      raise suggestions for school nurses. Such nurses should provide health promotion
      programs to promote the health of children whose mothers are foreign wives. This
      will enable these children to grow up happily and healthily, and develop into
      healthy, well-educated adults with a positive attitude and good health-related
      behavior.

PMID- 15864765
TI  - [Case management for school students with chronic disease: the current situation
      and future direction].
AB  - This paper aims to investigate the importance of management of chronic illness in
      schools epidemiological data. By examining the current state of such management,
      we found that school nurses, family members, mentors and school administrators
      lack sufficient knowledge to conduct effective case management for students with
      chronic diseases. This paper seeks to indicate principles for the conduct of case
      management of chronic disease in Taiwan. Incorporating practices, regulations,
      information systems, policy, and evaluation systems, recommendations are made
      with the hope that a well-planned system of case management of chronic disease
      can be established in schools to further enhance the quality of health care and
      life generally for school children.

PMID- 15864766
TI  - [Health promoting schools: a new era in school nursing].
AB  - Health promotion schools, introduced by the World Health Organization in 1996,
      represent a new model for school health. They consist of six working areas, and
      reflect the spirit of the 1987 Ottawa Charter for Health Promotion, which aims to
      place the foundations of health promotion work in schools. This article
      introduces the development of health promotion schools, both in Taiwan and
      overseas, outlines their structure, and compares and contrasts the models
      represented by traditional school health, integrated school health, and the
      health promotion schools. The roles of school health nurses are summarized as
      follows: health service provider, health education initiator, health counselor,
      leader of health promotion activity and integrator of community resources.
      Suggestions are made for future development, including: (1) a need to conduct the
      research, in order to evaluate and provide evidence of outcome effectiveness, (2)
      a need to establish standardized indicators concerning school health nursing, and
      (3)Education and health should be integrated in the health promotion schools.

PMID- 15864767
TI  - [The effectiveness of the video-based Lamaze method on prenatal mothers'
      knowledge, attitudes, and practice].
AB  - This study was conducted to explore the effectiveness of the video-based Lamaze
      method on pre-natal mothers' knowledge and attitudes, compared with that of
      traditional nursing guidelines. Using a quasi-experimental design, women in labor
      with gestations of 32 weeks or more were divided into four study groups,
      including two experimental groups (E(1): issued with traditional nursing
      guidelines and instructed in video-based Lamaze method; and E(2): instructed in
      video-based Lamaze method), and two control groups (C(1): issued with traditional
      nursing guidelines and C(2): issued with no guidelines). Before the intervention,
      E(1) had the highest score for knowledge. Scores for attitude showed no
      significant difference between the four groups. The experimental groups had
      higher scores than the control groups in the posttest. With the exception of the
      scores for attitude (E(1) > E(2)), knowledge (E(1): 13.09 +/- 1.40, E(2): 12.40
      +/- 1.17) and management of the labor process (E(1): 119.00 +/- 10.91, E(2):
      112.97 +/- 14.33) there were no significant differences between E(1) and E(2) in
      the posttest. Correlation analysis showed that the higher the scores for prenatal
      knowledge, the better the performance in prenatal practice, postnatal knowledge,
      attitude, and management of the labor process. The more positive the prenatal
      attitude, the better the performance in postnatal knowledge, attitude, and
      management of the labor process. The higher the scores in prenatal practice, the
      better the performance in postnatal knowledge, attitude, and management of the
      labor process. Positive associations were also found between postnatal knowledge,
      attitude, and management of the labor process. This study showed that the video
      based Lamaze method is likely to promote more effectively than traditional
      guidelines the knowledge, attitudes, and practice of prenatal mothers in relation
      to giving birth. The use of this method in conjunction with traditional nursing
      guidelines may be even more effective in relation to maternal attitude.

PMID- 15864768
TI  - [Improving the facial skin and oral mucosa integrity of patients with oral
      endotracheal intubation].
AB  - The problems of damage to facial skin and oral mucus affecting intubated patients
      have seldom been effectively improved. The purpose of this project was to reduce
      the incidence of defects in facial skin and oral mucosa integrity in patients
      with oral endotracheal intubation. The main factors identified by data collection
      were: 1. Inappropriate endotracheal tube securement. 2. Dry lip mucosa. 3.
      Pressure points caused by large bite-blocks. 4. Patient's frequent movement of
      mouth. 5. Allergic reaction caused by adhesive tape. Through the implementation
      of a new standard for oral endotracheal tube securement and the application of
      new bite-blocks to deal with the problems mentioned above, the incidence rate of
      defects in facial skin and oral mucosa integrity decreased from 67% to 25%. The
      results indicate that the new standard of securement and the new bite-block can
      help to solve these problems.

PMID- 15864769
TI  - [Crisis management and medical disputes related to nursing practice].
AB  - The number of medical dispute cases has been increasing, due to uncertainties
      about medical care quality and outcomes as well as the increased influence of
      consumer-centered ideology. This situation has created difficulties in the
      relationships between patients/family members and health care providers. This
      paper focuses on discussing crisis management and medical disputes as related to
      nursing practice. Reviewed literature was organized into four parts:
      understanding crisis management; crises in medical institutions; nursing
      practice, medical disputes and crisis management; practical implications. The
      information included in this paper might improve nurses' and administrators'
      knowledge of crisis management, enhance the implementation of crisis management
      strategies in medical disputes, and reduce financial losses and psychological
      distress resulting from inappropriate crisis management.

PMID- 15864770
TI  - [The process of curriculum redesign for the nursing baccalaureate program: an
      analysis of teacher actions].
AB  - The purpose of this study is to define the teacher's actions in the process of
      developing a new curriculum for the Faculty of Nursing, in National Yang-Ming
      University. The authors defined three tasks of teachers developing the
      curriculum: Relocating, strategizing, and reflective practice. Relocating implied
      reflecting on the dilemmas of nursing education, world trends in nursing
      education, the experience of medical schools with problem-based learning, and the
      philosophy of the university. Strategizing meant developing guidelines that
      included humanistic education, faculty development, and course content of the new
      curriculum. Reflective practice included intersubject integration, dialogue
      teaching, and shifting the focus from hospital care to community and family care.

PMID- 15864771
TI  - [Coping: a concept analysis].
AB  - Hundreds of studies have been conducted by nuring researchers on stressors
      requiring coping. Unfortunately, the concept of coping is poorly defined. This
      paper presents a conceptual analysis of the phenomenon of coping. Within the
      classic framework developed by Walker and Avant (1995), coping is analyzed and
      critical attributes are distilled. A model case, a related case and a contrary
      case are constructed as conceptual clarity is established. Empirical referents
      that exemplify the concept of coping are identified. The concept analysis
      provides a forum for dialectics, offering one defensible interpretation of a
      complex human occurrence. The implications for nursing are discussed in the
      conclusion.

PMID- 15864772
TI  - [Oxygen therapy care].
AB  - Oxygen therapy is administered to patients who require enhanced oxygenation of
      their arterial blood, patients with, for example, respiratory conditions which
      have resulted in impaired gaseous exchanges in the lungs, or many conditions that
      impair oxygen delivery to the tissues, such as myocardial infarction. Generally
      speaking, oxygen is an effective drug which is used very commonly in clinics.
      From internal medical problems, to emergency situations, even surgical problems,
      all of us care for patients receiving oxygen therapy sometimes. Regardless of the
      nurse's knowledge and skills in relation to oxygen therapy, the key nursing role
      is to support and reassure the patient and gain his or her confidence in order to
      maintain compliance with the treatment. This article discusses the
      pathophysiological changes associated with hypoxia, oxygen delivery devices, and
      guidelines for caring for patients requiring supplemental oxygen. We expect this
      article to contribute to improvements in the quality of clinical oxygen therapy.

PMID- 15864773
TI  - [Nursing care in the conduct of alveolar lavage].
AB  - Pulmonary alveolar proteinosis (PAP) is a rare disease reported to affect adults
      between the ages of 20 and 50, in a male:female ratio of 2-3:1. Alveolar lavage
      is the most effective proven treatment. This article introduces PAP, alveolar
      lavage and nursing intervention in preparation, during, and after the procedure,
      and home care. We hope this article can provide new information on the nursing
      care necessary for patients with PAP.

PMID- 15864774
TI  - [An experience in nursing an acute lymphocytic leukemia patient with Peripherally
      Inserted Central Catheter].
AB  - The Peripherally Inserted Central Catheter (PICC) is still in its infancy in
      Taiwan. It has many advantages, including safety, simplicity, and few
      complications during the insertion process. It is suitable for patients who need
      long-term parenteral administration of medication or chemotherapy. However, the
      duration of PICC implantation is around six months, or even up to one year. As a
      result, it is very important to educate patients to take care of themselves
      throughout the implantation period in order to prevent complications. This report
      describes the experience of nursing a forty-four-year old male patient who
      suffered from acute lymphocytic leukemia and received a PICC implantation while
      undergoing chemotherapy treatment. As a PICC case manager, the author utilized
      self-efficacy theory and devoted herself to nursing care, interviews and phone
      calls to collect valuable information. During the process of PICC implantation,
      the author analyzed the characteristics of this case and assisted the patient and
      his primary care giver in choosing a suitable catheter and self-care techniques
      to achieve minimal complications during implantation. It is hoped that, by
      sharing in her experience, nursing staff may enhance their ability to assist
      patients with PICC and to help them to maintain their quality of life.

PMID- 15864775
TI  - [Nursing experience: discharge planning for a disabled elderly patient].
AB  - This case study describes the comprehensive and continuous care provided to an
      elderly patient whose self-care ability had been lost in a traffic accident.
      During the nursing period, from March 4th 2004 to May 18th 2004, we utilized the
      literature on the health problems of the elderly, concepts of discharge planning,
      and a comprehensive nursing assessment to confirm that the main nursing issues
      were clearance of a blocked airway, and impaired mobility. We also helped
      caregivers to cope with the problems of role strain. During the nursing process,
      we placed particular emphasis on management and preparation for care after
      discharge, the training of a maid, and psychological support for the family. The
      experience enabled surgical ward nurses who were already used to fast discharges
      of patients to gain a better understanding of discharge planning in complex cases
      involving the disabled elderly.

PMID- 15864776
TI  - Lipopolysaccharide primes neutrophils for a rapid response to IL-10.
AB  - Responsiveness of human neutrophils to IL-10 was recently shown to be strictly
      dependent on the levels of IL-10R1 expression. Activation of signal transducer
      and activator of transcription 3 (STAT3) phosphorylation and induction of
      suppressor of cytokine signaling (SOCS)-3 protein by IL-10 are in fact negligible
      in circulating or freshly isolated ("time 0") neutrophils, but become readily
      measurable in neutrophils cultured for 4 h in the presence or absence of LPS. In
      this study, we show that modulation by IL-10 of LPS-induced TNF-alpha, CXCL8/IL-8
      and IL-1 receptor antagonist (IL-1ra) mRNA accumulation in neutrophils already
      expressing a functional IL-10R and antigenic SOCS-3 (i.e. in "4-h-cultured"
      neutrophils) occurs with kinetics that are similar to those observed in "time 0"
      neutrophils, depends on de novo protein synthesis, but does not require SOCS-1,
      SOCS-3, heme oxygenase and Bcl-3 induction. By contrast, we show that IL-10 alone
      rapidly modulates the expression of TNF-alpha, CXCL8/IL-8 and IL-1ra mRNA,
      without any new protein synthesis requirement, if neutrophils have been
      previously exposed to LPS for at least 4 h. These findings suggest that LPS
      prepares neutrophils to optimally respond to IL-10 in terms of rapid gene
      modulation via mechanisms that, presumably, depend on specific LPS-induced
      protein(s).

PMID- 15864777
TI  - Expression of MHC class I receptors confers functional intraclonal heterogeneity
      to a reactive expansion of gammadelta T cells.
AB  - NK cell receptors for MHC class I molecules (MHC-NKR) can be expressed by T cell
      subsets. The restricted repertoire and phenotypic characteristics of MHC-NKR(+) T
      cells indicate that expression of MHC-NKR is acquired upon antigenic challenge
      and might promote expansion of T cells. Previous studies performed on in vitro
      generated alphabeta T cell clones concluded that MHC-NKR expression was not a
      clonal attribute. Here, we examined a massive monoclonal expansion of a non
      leukemic gammadelta T cell population found in the peripheral blood of a lung
      transplanted patient who suffered from a cytomegalovirus infection. Despite their
      monoclonality, these T cells displayed a heterogeneous and stable in vivo Ig- and
      lectin-like MHC-NKR phenotype. Twenty percent of the cells displayed a
      CD94(+)NKG2A(+) phenotype, and 10% were labeled with an anti-CD158b1/b2/j
      monoclonal antibody. A CD158b/j(+) gammadelta T cell clone derived in vitro from
      patient's peripheral blood lymphocytes was shown to express the activating form
      CD158j (KIR2DS2), which once cross-linked stimulated the clone cytolytic function
      and costimulated the TCR-induced production of cytokines, independently of the
      killer-activating receptor-associated protein (KARAP). In conclusion,
      heterogeneity of MHC-NKR expression confers a functional intraclonal diversity
      that may participate to induction of specific gammadelta T cell effector
      functions or proliferation upon pathogen challenge.

PMID- 15864778
TI  - Depletion of immature B cells during Trypanosoma cruzi infection: involvement of
      myeloid cells and the cyclooxygenase pathway.
AB  - The ability of a microorganism to elicit or evade B cell responses represents a
      determinant factor for the final outcome of an infection. Although pathogens may
      subvert humoral responses at different stages of B cell development, most studies
      addressing the impact of an infection on the B cell compartment have focused on
      mature B cells within peripheral lymphoid organs. Herein, we report that a
      protozoan infection, i.e. a Trypanosoma cruzi infection, induces a marked loss of
      immature B cells in the BM, which also compromises recently emigrated B cells in
      the periphery. The depletion of BM immature B cells is associated with an
      increased rate of apoptosis mediated by a parasite-indirect mechanism in a
      Fas/FasL-independent fashion. Finally, we demonstrated that myeloid cells play an
      important role in B cell depletion, since CD11b(+) BM cells from infected mice
      secrete a product of the cyclooxygenase pathway that eliminates immature B cells.
      These results highlight a previously unrecognized maneuver used by a protozoan
      parasite to disable B cell generation, limiting host defense and favoring its
      chronic establishment.

PMID- 15864779
TI  - Immune responses to Plasmodium vivax pre-erythrocytic stage antigens in naturally
      exposed Duffy-negative humans: a potential model for identification of liver
      stage antigens.
AB  - Duffy antigen is the receptor used by Plasmodium vivax to invade erythrocytes.
      Consequently, individuals lacking Duffy antigen [Fy(-)] do not develop blood
      stage infections. We hypothesized that naturally exposed Fy(-) humans may develop
      immune responses mainly to pre-erythrocytic stages and could be used to study
      acquired immunity to P. vivax and to identify liver-stage antigens. We report
      here that antibody and IFN-gamma responses to known sporozoite antigens were
      significantly induced by natural exposure in Fy(-) humans, whereas responses to
      blood-stage antigens were significantly induced in Fy(+) humans. IFN-gamma
      responses to sporozoite antigens were lower in Fy(+) than in Fy(-) humans,
      indicating that in Fy(+) humans blood-stage infections may have suppressed T cell
      responses to pre-erythrocytic stages. We evaluated the immune responses to 18
      novel P. vivax homologs of P. falciparum sporozoite proteins identified from the
      P. vivax genome sequence. Eight proteins recalled IFN-gamma responses in P. vivax
      exposed but not in unexposed individuals. Of these, 3 antigens elicited IFN-gamma
      responses in Fy(-) but not in Fy(+) individuals. These results suggest that
      differential immune responses observed in naturally exposed Fy(-) and Fy(+)
      individuals can be exploited to identify P. vivax stage-specific antigens.

PMID- 15864780
TI  - New mechanisms of skin innate immunity: ASK1-mediated keratinocyte
      differentiation regulates the expression of beta-defensins, LL37, and TLR2.
AB  - Epidermal keratinocytes differentiate and form a multilayered epidermis, which is
      the primary barrier between the body and the outer environment. As the epidermis
      is constantly exposed to a variety of microbial pathogens, its function of
      resisting microbial pathogens is vital. This characteristic feature is formed
      during differentiation. Immunohistochemical analysis revealed that the upper
      epidermis of normal human skin expresses beta-defensins 1-3 and LL37. We
      hypothesized that epidermal keratinocytes develop an innate immune barrier based
      on human beta-defensins (hBD) and LL37 during differentiation. To prove this, we
      introduced an active form of the apoptosis signal-regulating kinase-1 (ASK1), an
      intracellular regulator of keratinocyte differentiation, into cultured normal
      human keratinocytes. Transfection of this active form, ASK1-DeltaN, significantly
      enhanced the expression of hBD1-3 and LL37. In addition, a p38 inhibitor
      abolished this induction, indicating that the ASK1-p38 cascade regulates the
      expression of hBD1-3 and LL37. Furthermore, the ASK1-p38 pathway also regulated
      the expression of Toll-like receptor (TLR)2 in keratinocytes. Contact between S.
      aureus and keratinocytes resulted in the phosphorylation of p38 and induced the
      expression of hBD2 and hBD3. Moreover, the p38 inhibitor reduced this induction.
      In conclusion, the ASK1-p38 cascade regulates the innate immunity of the skin by
      forming an immune barrier consisting of hBD, LL37, and TLR2 during epidermal
      differentiation.

PMID- 15864781
TI  - Cerebrospinal fluid T cell clones from patients with multiple sclerosis:
      recognition of idiotopes on monoclonal IgG secreted by autologous cerebrospinal
      fluid B cells.
AB  - Due to somatic recombination and hypermutation, Ig variable heavy (V(H)) and
      light (V(L)) regions contain unique immunogenic determinants, idiotopes (Id),
      which can stimulate T cells. To address the relevance of this in a human disease,
      monoclonal IgG (mAb)-secreting B cell clones were established from the
      cerebrospinal fluid (CSF) of two patients with multiple sclerosis (MS). HLA-DR
      restricted CD4(+) T cell lines and clones from CSF of both patients specifically
      recognized autologous CSF mAb. The CSF T cell clones produced IFN-gamma; some
      also produced TNF-alpha, IL-10 and IL-5. V(H) and V(L) on the monoclonal IgG
      derived from CSF B cells expressed amino acid replacements due to somatic
      mutations. A T cell epitope was mapped to a V(H) framework region, where an amino
      acid replacement was critical for the T cell recognition. The finding of Id
      specific T cells and Id-bearing B cells in the CSF indicates that they coexist
      within the diseased organ, and provide a basis for the study of Id-driven T-B
      cell collaboration in a human autoimmune disease.

PMID- 15864782
TI  - Endothelial inducible costimulator ligand expression is increased during human
      cardiac allograft rejection and regulates endothelial cell-dependent allo
      activation of CD8+ T cells in vitro.
AB  - The role of costimulatory molecules other than CD80/CD86 in endothelial cell (EC)
      dependent CD8(+) T cell activation including the generation of a distinct subset
      of endothelium-specific CTL (EC-CTL) remains unclear. Inducible costimulator
      (ICOS) and its ligand (ICOSL) are new members of the CD28 family mediating
      effector T cell differentiation and graft rejection in animal models. In this
      study endothelial ICOSL expression/regulation and effects on CD8(+) T cell allo
      activation were analyzed. Constitutive expression of ICOSL was found on human EC.
      IL-1alpha and TNF-alpha induced ICOSL in an NF-kappaB-dependent manner on human
      umbilical vein endothelial cells (HUVEC). ICOS receptor was not detected on
      resting CD8(+) T cells but was induced in co-cultures with HUVEC. ICOSL blockade
      reduced CD8(+) T cell proliferation by 70% along with a marked decrease of IL-2
      and IFN-gamma production in co-cultures with HUVEC. IL-2 supplementation of co
      cultures could overcome the effect of ICOSL blockade; similarly the generation of
      EC-CTL was not impaired by ICOSL blockade in an IL-2-containing system. In vivo,
      weak constitutive ICOSL expression was found on coronary microvessels, which was
      significantly up-regulated during acute cardiac allograft rejection (p=0.04). Our
      data indicate a distinct role for ICOSL in EC-mediated CD8(+) T cell
      costimulation with implications for human cardiac allograft rejection.

PMID- 15864783
TI  - Dietary fibre and colorectal cancer: a model for environment--gene interactions.
AB  - As environmental factors are clearly associated with risk for colorectal cancer,
      we set out to model how dietary fibre, or the effects of its ingestion, might
      impact upon the complex events that characterise colorectal oncogenesis. The
      diverse nature of dietary fibre and its resultant fate in the gut is outlined.
      The evidence indicates that different types of fibre create different conditions
      in different regions of the gut. This is reflected in different effects on
      oncogenesis especially in animal models. Data from animal models show that
      insoluble fibre is protective. Evidence from human studies are not consistent,
      especially considering the interventional studies. However, all such studies have
      been dependent on biomarkers short of cancer formation, for measurement of an
      effect. The biological and molecular events characteristic of colorectal
      oncogenesis are reviewed in an effort to identify how fibre ingestion might
      regulate oncogenesis. While several mechanisms might account for protection, the
      results of fermentation and especially butyrate production provide examples of
      how genomic instability might be controlled. Activation of apoptosis and cell
      cycle arrest seem likely to be mechanisms that would enable correction of genomic
      events that drive oncogenesis. Butyrate itself can regulate gene expression by
      both epigenetic and direct effects.

PMID- 15864784
TI  - Association of non-starch polysaccharides and ferulic acid in grain amaranth
      (Amaranthus caudatus L.) dietary fiber.
AB  - The association of ferulic acid, an alkali-extractable phenolic acid in amaranth
      (Amaranthus caudatus L., Amaranthaceae) insoluble fiber (trans-ferulic acid: 620
      microg.g-1, cis-ferulic acid: 203 microg.g-1), and non-starch polysaccharides was
      investigated. Enzymatic hydrolysis of insoluble amaranth fiber released several
      feruloylated oligosaccharides that were separated using Sephadex LH-20
      chromatography and reversed phase-high performance liquid chromatography (RP
      HPLC). Three compounds were unambiguously identified: O-(6-O-trans-feruloyl-beta
      D-galactopyranosyl)-(1-->4)-D-galactopyranose, O-(2-O-trans-feruloyl-alpha-L
      arabinofuranosyl)-(1-->5)-L-arabinofuranose, and O-alpha-L-arabinofuranosyl-(1-
      >3)-O-(2-O-trans-feruloyl-alpha-L-arabinofuranosyl)-(1-->5)-L-arabinofuranose.
      These feruloylated oligosaccharides show that ferulic acid is predominantly bound
      to pectic arabinans and galactans in amaranth insoluble fiber. 5-O-trans-Feruloyl
      L-arabinofuranose was the only compound isolated in pure form from an acid
      hydrolyzate. This compound may have its origin from pectic arabinans but also
      from arabinoxylans.

PMID- 15864785
TI  - 6-substituted purines as inhibitors of 15-lipoxygenase; a structure-activity
      study.
AB  - 15-lipoxygenase (15-LO) has been implicated in oxidation of low-density
      lipoproteins (LDL), a process believed to be important for the development of
      atherosclerosis, as well as other pathogenic conditions. Potent and selective
      inhibitors of 15-LO may have a drug potential. In this study, purines with a
      variety of substituents have been examined as inhibitors of 15-lipoxygenase (15
      LO) from soybeans. Several 6-substitued purines where the purine ring and a
      phenyl ring in the substituent were separated by a "spacer" were synthesized and
      their ability to inhibit the enzyme was explored. Sepa ration of the purine and
      the phenyl rings with none, one or two sp3-carbons resulted in essentially
      inactive compounds, trans-styrylpurines and phenylethynylpurines, on the other
      hand, they exhibited activity close to the well-known 15-LO inhibitor quercetin.
      High activity was also found when the "spacer" was a trans-cyclopropyl ring. The
      shape of the spacer was important; a corresponding cis-cyclopropylpurine
      exhibited much less affinity for the enzyme. Only minor differences in inhibitory
      activity against 15-LO were found regardless of whether an N-substituent was
      situated on N-9 or N-7, even when the N-substituent was relatively large. Also, a
      variety of substituents in the purine 2- and 8-position were well tolerated.

PMID- 15864786
TI  - Novel pyrazole derivatives as potential promising anti-inflammatory antimicrobial
      agents.
AB  - Four series of 1H-pyrazole derivatives have been synthesized. The first series
      was synthesized starting by condensing the hydrazine derivatives 1a-d with 4-(1
      ethoxycarbonyl-2-oxopropyl)azobenzoic acid 2a in ethanol or glacial acetic acid
      to generate the corresponding pyrazoline derivatives 3a-d. Likewise, heating 1a-d
      with 4-(1-acetyl-2-oxopropyl)azobenzoic acid 2b gave rise to the pyrazole
      derivatives 4a-d. Similarly, reaction of 1a-d with ethyl 2-(1,5-dimethyl-3-oxo-2
      phenyl-2,3-dihydro-1H-pyrazol-4-ylazo)-3-oxobutanoate 2c or 3-(1,5-dimethyl-3-oxo
      2-phenyl-2,3-dihydro-1H-pyrazol-4-yl azo)pentane-2,4-dione 2d in ethanol or
      glacial acetic acid led to the corresponding pyrazoline derivatives 5a-d or
      pyrazole derivatives 6a-d. The newly synthesized compounds were evaluated for
      their anti-inflammatory-antimicrobial activities. In addition, the ulcerogenic
      and acute toxicity profiles were determined. Compound 6c, proved to be the most
      active anti-inflammatory-antimicrobial agent in the present study with a good
      safety margin and no ulcerogenic effect.

PMID- 15864787
TI  - Synthesis and in vitro antioxidant activity of some new fused pyridine analogs.
AB  - A new series of pyrano[3,2-c]pyridines, pyrazolo[4,3-c]pyridines, and pyrido[4,3
      d]pyrimidines were synthesized and screened for their in vitro antioxidant
      activity. Compounds 13, 14, 15, 23, 29, 30, and 31 exhibited the most active
      oxygen free-radical scavenger activity with percentage inhibitions of 99.4, 99.6,
      99.8, 97.3, 99.0, 99.3, and 99.5%; respectively, which is comparable to the
      curcumin potency. Most of the tested compounds proved to be safe towards
      peripheral multinuclear neutrophils (PMNs). The detailed synthesis and
      antioxidant activity data are reported.

PMID- 15864788
TI  - Synthesis and antitumor activity of some curcumin analogs.
AB  - In this study, four new curcurmin analogs (compounds 1, 2, 17 and 18) were
      synthesized. 17 [3,5-bis(4-hydroxy-3-methoxy-5-methylcinnamyl)N-methylpiperidone]
      showed high activity with GI50, TGI, and LC50 MG-MID values of 21.3, 70.7, and
      97.7 microM, respectively. 18 [3,5-bis(4-hydroxy-3-methoxy-5-methylcinnamyl)-N
      ethylpiperidone] showed the highest activity in this study with GI50, TGI, LC50
      MG-MID values of 4.4, 33.8, 89.1 microM, respectively. 18 is even more active
      than curcumin with GI50, TGI, LC50 MG-MID values of 38.4, 35.6, 66.0 microM;
      respectively. 8 showed moderate selectivity towards Leukemia cell line-subpanel
      with a ratio of 5.6 (curcumin ratio: 1.2 for the same subpanel). The in vitro
      anti-tumor screening reveals that the results go hand in hand with the in vitro
      free radical scavenging effects. The antioxidant effect of these compounds
      depends mainly on the stabilization of the formed phenoxy free radical for which
      the p-hydroxy phenyl moiety is essential. o-substitution by electron-donating
      groups like the o-methoxy group (and to a even higher degree by the ethoxy group)
      increases the stability of phenoxy free radical, hence increasing both free
      scavenging and anti-tumor effects. Increasing the alkyl group chain on the N in
      the series of substituted N-alkyl piperidones as well as the extension of
      conjugation, increases the stabilization of phenoxy free radical and thereby the
      activity towards both free radical scavenging and anti-tumor effects. This may be
      attributed to an increased positive inductive effect and/or increased
      lipophilicity of the new compounds, a fact which is proven by the superior
      activities of compounds 17 and 18.

PMID- 15864789
TI  - Extractive spectrophotometric methods for the determination of oxomemazine
      hydrochloride in bulk and pharmaceutical formulations using bromocresol green,
      bromocresol purple and bromophenol blue.
AB  - Three simple, sensitive and accurate spectrophotometric methods have been
      developed for the determination of oxomemazine hydrochloride in bulk and
      pharmaceutical formulations. These methods are based on the formation of yellow
      ion-pair complexes between the examined drug and bromocresol green (BCG),
      bromocresol purple (BCP), and bromophenol blue (BPB) as sulphophthalein dyes in
      acetate-HCl buffer of pH 3.6, 3.4, and 4.0, respectively. The formed complexes
      were extracted with dichloromethane and measured at 405 nm for all three systems.
      The best conditions of the reactions were studied and optimized. Beer's law was
      obeyed in the concentration ranges 2.0-12, 2.0-13, and 2.0-14 microg mL(-1) with
      molar absorptivities of 3.2 x 10(4), 3.7 x 10(4), and 3.1 x 10(4) L mol(-1) cm(
      1) for the BCG, BCP, and BPB methods, respectively. Sandell's sensitivity,
      correlation coefficient, detection and quantification limits are also calculated.
      The proposed methods have been applied successfully for the analysis of the drug
      in pure form and in its dosage forms. No interference was observed from common
      pharmaceutical excipients. Statistical comparison of the results with those
      obtained by HPLC method shows excellent agreement and indicates no significant
      difference in accuracy and precision.

PMID- 15864790
TI  - Dietary fibres as "prebiotics": implications for colorectal cancer.
AB  - A "prebiotic" is a nondigestible food ingredient whose beneficial effects on the
      host result from the selective stimulation of growth and/or activity of members
      of the bacterial community that inhabits the human bowel (the gut microbiota).
      Although much of the prebiotic literature focuses on nondigestible
      oligosaccharides, such as oligofructose, most dietary fibres that are fermentable
      carbohydrates could be considered as prebiotics. Early studies suggested that
      colonic bacteria were risk factors for colon cancer. However, altering the
      composition or metabolic activity of the bowel microbiota through the use of
      dietary fibre might be important in reducing the prevalence of colorectal cancer.
      Mechanisms for beneficial effects of prebiotics might include changing the
      activity of exogenous carcinogens through modulating metabolic activation and/or
      detoxification, or stimulating the production of the short-chain fatty acid,
      butyrate. However, modern analytical techniques suggest that an important
      consequence of a modified bacterial community could be a change in the expression
      not only of a range of different bacterial genes in bowel contents, but also in
      the bowel mucosa of the host. Analogous with observations with probiotics, the
      stimulation of cytokines and modification of immune responses could be important
      in producing beneficial effects. Compared with transitory effects of probiotics,
      the prebiotic action of fermentable carbohydrates potentially provide the
      opportunity for sustainable modulation of activity of the gut microbiota.
      However, their mechanisms of action in humans are speculative, and research aimed
      at providing an integrated view of the gut microbiota and dietary fibre nutrition
      of humans needs to be developed.

PMID- 15864791
TI  - Production and characterisation of two wheat-bran fractions: an aleurone-rich and
      a pericarp-rich fraction.
AB  - Wheat bran is a good source of dietary fibre in the form of cell walls, but
      contains a number of different cell types. We describe a large-scale procedure
      for the production of an aleurone-rich and a pericarp-rich fraction from hard,
      Australian wheat. The fractions were characterised by field-emission scanning
      electron microscopy, by using a range of bright-field stains, colour reagents,
      and fluorochromes, and by chemical analysis of the walls. The aleurone fraction
      included the seed coat with its cuticle. Only the pericarp walls showed a
      histochemical reaction for lignin. The concentrations of ester-linked ferulic
      acid and (1-->3),(1-->4)-beta-glucans were greater in the aleurone-rich fraction
      than in the pericarp-rich fraction. The results are consistent with the
      arabinoxylans in the walls of the pericarp-rich fraction being more highly
      substituted with arabinose than those in the walls of the aleurone-rich fraction.
      When the fractions were fed as a dietary supplement to rats and walls were
      isolated from the faeces, it was found that the pericarp walls were not degraded,
      but the aleurone walls were partially degraded.

PMID- 15864792
TI  - Organocatalytic hydride transfers: a new concept in asymmetric hydrogenations.

PMID- 15864793
TI  - Study of anisotropic interfacial electron transfer across a
      semiconductor/solution interface by time-resolved EPR spectroscopy.

PMID- 15864794
TI  - Coordinatively unsaturated cationic and zwitterionic [Cp*Ru(kappa2-P,N)]
      complexes: ligand-assisted double-geminal C-H bond activation and reversible
      alpha-H elimination at ruthenium.

PMID- 15864795
TI  - Weak CH...F bridges and internal dynamics in the CH3F.CHF3 molecular complex.

PMID- 15864796
TI  - Novel phthalocyaninatobis(alkylcarboxylato)silicon(IV) compounds: NMR data and X
      ray structures to study the spacing provided by long hydrocarbon tails that
      enhance their solubility.
AB  - The reaction between trans-PcSiCl2 (1) and the potassium salts of six fatty acids
      (2 a-2 f) led to the trans-PcSi[OOC(CH2)nCH3]2 compounds (3 a-3 f), which were
      characterised by elemental analysis, IR, UV/Vis and 1H, 13C, and 29Si NMR
      spectroscopy. From a detailed study of the NMR spectra, the strong anisotropic
      currents of the Pc macrocycle were found to have an effect on up to the sixth
      methylenic group. As expected, the length of the hydrocarbon tail does not affect
      the chemical shift of the 29Si nucleus of any of the compounds, appearing at
      around -222.6. The structures of PcSi[OOC(CH2)nCH3]2, where n = 7, 10, 12, 13 and
      20, were determined by X-ray crystallography. All the compounds were found to be
      triclinic with a P1 space group. In all cases the observed crystallographic
      pseudosymmetry is Ci and the asymmetric unit consists of half a molecule. The
      silicon atom is at the centre of a distorted octahedron and hence its
      coordination number is six. The carboxylate fragments are in a trans
      configuration with respect to the Pc macrocycle. The supramolecular structures
      are discussed in detail herein. The correlation between the 1H NMR chemical
      shifts and the position of the corresponding carbon atoms in the hydrocarbon tail
      reveals that the dicarboxylate substituents exhibit a spacer-like behaviour that
      enhances the solubility. A detailed study of the tail variable allowed us to
      evaluate the loss of radial shielding along the Pc2- ligand.

PMID- 15864797
TI  - Anisotropic hyperfine interaction in the manganese(III) hexaaqua ion.

PMID- 15864798
TI  - Transition metal complexes coordinated by an NAD(P)H model compound and their
      enhanced hydride-donating abilities in the presence of a base.
AB  - The ruthenium(II) and rhenium(I) complexes containing an NAD(P)H model compound,
      1-benzyl-1,4-dihydronicotinamide (BNAH), as ligand, [Ru(tpy)(bpy)(BNAH)]2+ (1 a)
      and [Re(bpy)(CO)3(BNAH)]+ (1 b), were quantitatively produced by the reaction of
      the corresponding metal hydrido complexes with BNA(+) (1-benzylnicotinamidium
      cation). In the presence of base with pK(a) = 8.9, 1 a and 1 b have much greater
      reducing power than "free" BNAH. The oxidation potentials of 1 a in the absence
      and the presence of triethylamine were 0.55 V and -0.04 V, respectively, versus
      Ag/AgNO(3), whereas that of "free" BNAH was 0.30 V. Spectroscopic results clearly
      showed that the base extracts a proton from the carbamoyl group on 1 a and 1 b to
      give the deprotonated BNAH coordinating to the transition-metal complexes
      [Ru(tpy)(bpy)(BNAH-H+)]+ (3 a) and [Re(bpy)(CO)3(BNAH-H+)] (3 b); this
      deprotonation underlies the enhancement in reducing ability. The deprotonated
      forms 3 a and 3 b can efficiently reduce other NAD(P) models to give the
      corresponding 1,4-dihydro form, resulting in the deprotonated BNA+ being
      coordinated to the metal complexes [Ru(tpy)(bpy)(BNA(+)-H+)]2+ (2 a) and
      [Re(bpy)(CO)3(BNA+-H+)]+ (2 b); "free" BNAH and the protonated adducts 1 a and 1
      b cannot act in this way. X-ray crystallography was performed on the PF6- salt of
      2 a, and showed that the deprotonated nitrogen atom on the carbamoyl group
      coordinates to the ruthenium(II) metal center with a bond length of 2.086(3)
      Angstroms. Infrared spectral data suggested that the deprotonated carbamoyl group
      on the reduced forms 3 a and 3 b is converted to the imido group, and that the
      oxygen atom coordinates to the metal center.

PMID- 15864799
TI  - Absolute configuration of C2-symmetric spiroselenurane: 3,3,3',3'-tetramethyl
      1,1'-spirobi[3 H,2,1]benzoxaselenole.
AB  - The enantiomers of 3,3,3',3'-tetramethyl-1,1'-spirobi[3 H,2,1]benzoxaselenole
      have been separated on a chiral preparative chromatographic column. The
      experimental vibrational circular dichroism (VCD) spectra have been obtained for
      both enantiomers in CH(2)Cl(2). The theoretical VCD spectra have been obtained by
      means of density functional theoretical calculations with the B3 LYP density
      functional. From a comparison of experimental and theoretical VCD spectra, the
      absolute configuration of an enantiomer with positive specific rotation in
      CH(2)Cl(2) at 589 nm is determined to be R. This conclusion has been verified by
      comparing results of experimental optical rotatory dispersion (ORD) and
      electronic circular dichroism (ECD) to predictions of the same properties using
      the B3 LYP functional for the title compound.

PMID- 15864800
TI  - Osteopontin induces multiple changes in gene expression that reflect the six
      "hallmarks of cancer" in a model of breast cancer progression.
AB  - Tumor progression is a multistep process, which enables cells to evolve from
      benign to malignant tumors. This progression has been suggested to depend on six
      essential characteristics identified as the "hallmarks of cancer," which include:
      self-sufficiency in growth signals, insensitivity to growth-inhibitory signals,
      evasion of apoptosis, limitless replicative potential, sustained angiogenesis,
      and tissue invasion and metastasis. Osteopontin (OPN) is an integrin-binding
      protein that has been shown to be associated with the progression of several
      cancer types, and to play an important functional role in various aspects of
      malignancy, particularly tissue invasion and metastasis. Here we studied genes
      regulated by OPN in a model of human breast cancer using oligonucleotide
      microarray technology by comparing the gene-expression profiles of 21NT mammary
      carcinoma cells transfected to overexpress OPN versus mock-transfected control
      cells. From over 12,000 human genes, we identified 99 known human genes
      differentially regulated by OPN whose expression changed by at least 1.5-fold and
      showed statistically significant differences in mean expression levels between
      groups. Functional classification of these genes into the hallmarks of cancer
      categories showed that OPN can affect the expression of genes involved in all six
      categories in this model. Furthermore, we were able to validate the expression of
      18/19 selected candidate genes by quantitative real-time PCR, further supporting
      our microarray findings. This study provides the first evidence that OPN can lead
      to numerous gene expression changes that influence multiple aspects of tumor
      progression and malignant growth.

PMID- 15864801
TI  - Utility of the ammonia-free Birch reduction of electron-deficient pyrroles: total
      synthesis of the 20s proteasome inhibitor, clasto-lactacystin beta-lactone.
AB  - A new synthesis of the 20S proteasome inhibitor clasto-lactacystin beta-lactone
      is described. Our route to this important natural product involves the partial
      reduction of an electron deficient pyrrole as a key step. By judicious choice of
      enolate counterion, we were able to exert complete control over the
      stereoselectivity of the reduction/aldol reaction. Early attempts to complete the
      synthesis by using a C-4 methyl substituted pyrrole are described in full,
      together with our attempts to promote regioselective elimination of a tertiary
      alcohol. The lessons learnt from this first approach led us to develop another,
      and ultimately successful, route that introduced the C-4 methyl group at a late
      stage in the synthesis. Our successful route is then described and this contains
      several highly stereoselective steps including a cis-dihydroxylation and an
      enolate methylation. The final synthesis proceeds in just 13 steps and in 15 %
      overall yield making it an extremely efficient route to this valuable compound.

PMID- 15864802
TI  - The effect of PPARgamma ligands on UV- or chemically-induced carcinogenesis in
      mouse skin.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand
      activated transcription factor. There have been suggestions that PPARgamma
      ligands may have utility in preventing tumor development in rodent mammary glands
      and colon. The recent finding that mice lacking one allele of the PPARgamma gene
      were significantly more susceptible to 7,12-dimethylbenz[a]anthracene (DMBA)
      induced skin carcinogenesis compared to wild-type mice highlights mouse skin as
      another potential organ in which PPARgamma ligands may be effective as
      chemopreventive agents. In this study, we assessed the effect of two PPARgamma
      ligands (rosiglitazone and troglitazone) on UV and DMBA/12-O-tetradecanoylphorbol
      13-acetate (TPA)-induced mouse skin carcinogenesis, two of the most commonly used
      mouse skin carcinogenesis models. Unexpectedly, neither rosiglitazone (dietary
      200 ppm) nor troglitazone (topical 100 microg) significantly inhibited UV-induced
      skin tumor development in SKH-1 hairless mice. Likewise, dietary rosiglitazone
      did not statistically significantly inhibit DMBA/TPA-induced skin tumor
      development. Interestingly, dietary troglitazone significantly inhibited basal
      level keratinocyte proliferation as shown by 5-bromo-2'-deoxyuridine (BrdU)
      labeling, but it had no effect on TPA-induced epidermal cell proliferation.
      Northern blot analysis showed that PPARgamma expression was extremely low in
      normal mouse epidermis and was virtually undetectable in skin tumors.
      Collectively, our data suggest that PPARgamma ligands may not be useful in the
      prevention of chemically or UV-induced skin tumors.

PMID- 15864803
TI  - Contribution of the Src family of kinases to the appearance of malignant
      phenotypes in renal cancer cells.
AB  - Although the constitute activation of the Src family of kinases (Src) has been
      established as a poor prognostic factor in several types of cancer, the role of
      Src in renal cell carcinoma (RCC) has not been defined. This study aimed to
      determine whether Src could contribute to the appearance of malignant phenotypes
      in RCC. The role of Src in the appearance of malignant phenotypes in RCC was
      examined in two human renal cancer cell lines, Caki-1 from human metastatic RCC
      and ACHN from human primary RCC. Src activity in Caki-1 cells was higher than
      that in ACHN cells, and this difference corresponded to the difference of PP1 (a
      Src family inhibitor)-induced cytotoxicity on the two cells. The difference in
      cytotoxicity between the cells did not depend on cell cycle regulation but on the
      induction of apoptosis, and the difference in apoptosis particularly related to
      the reduction of the Bcl-xL level. Furthermore, in Caki-1 cells with higher Src
      activity, Src stimulated the production of vascular endothelial growth factor
      (VEGF), partially via the activation of Stat3, and the inhibition of Src activity
      caused a reduction of the VEGF level in serum, angiogenesis, and tumor
      development in a xenograft model. These results suggested that Src contributed to
      the appearance of malignant phenotypes in renal cancer cells, particularly due to
      the resistance against apoptosis by Bcl-xL and angiogenesis stimulated by Src
      Stat3-VEGF signaling.

PMID- 15864804
TI  - Method for coronary angiography in morbidly obese patients.
AB  - Cardiac catheterization in morbidly obese patients is difficult. In addition to
      problems regarding vascular access and radiographic penetration of the chest, the
      engineering parameters and physical limitations of the table and its supporting
      structures may limit these patients' ability to undergo clinically indicated
      coronary angiography. We describe a method for cardiac catheterization in which
      much of the obese patient's body weight is supported on a stretcher placed at
      right angles to the catheterization table, with only the thorax on the table
      under the image intensifier. Using this method, five consecutive successful
      diagnostic procedures and one coronary stent procedure have been performed
      without complication. Limitations of this procedure include inability to achieve
      the normal variety of angiographic views due to constraints on image intensifier
      rotation and skew.

PMID- 15864805
TI  - Three-year follow-up after intravascular gamma-radiation for in-stent restenosis
      in saphenous vein grafts.
AB  - The Washington Radiation for In-Stent Restenosis Trial in Saphenous Vein Grafts
      (SVG WRIST) demonstrated safety and efficacy of intravascular radiation therapy
      (IRT) for the treatment of in-stent restenosis (ISR) in SVG at 12 months. In this
      study, we aimed to examine whether the safety and efficacy of IRT is durable up
      to 36 months. One hundred twenty patients with diffuse ISR in SVG underwent
      balloon angioplasty, laser or atherectomy ablation, and/or additional stenting.
      After successful intervention, patients were randomly assigned in a double-blind
      fashion to intravascular treatment with a ribbon containing either iridium (Ir)
      192 (n = 60) or nonradioactive seeds (n = 60). The prescribed dose at 2 mm from
      the source was either 14 or 15 Gy in vessels 2.5-4.0 mm or 18 Gy in vessels > 4.0
      mm in diameter. At 36 months, target lesion revascularization (TLR; 43% vs. 66%;
      P = 0.02) and target lesion revascularization-major adverse cardiac event (TLR
      MACE; 49% vs. 71%; P = 0.02) rates continued to be lower in the IRT group, but
      both target vessel revascularization (TVR; 59% vs. 71%; P = 0.17) and TVR-MACE
      (63% vs. 77%; P = 0.11) rates were not. In SVG WRIST, patients with ISR treated
      with IRT had a marked reduction in the need for repeat TLR at 36 months, with
      sustained clinical benefit at 3 years despite late recurrences, which were more
      pronounced in the radiation group.

PMID- 15864806
TI  - Reproducibility and variability of activated clotting time measurements in the
      cardiac catheterization laboratory.
AB  - The objective of this study was to characterize the reproducibility and
      variability in the measurement to the activated clotting time (ACT) when
      performed on two different types of instruments, the HemoTec ACT (Medtronic) and
      the Hemochron 801 (International Technidyne). The ACT has evolved into the most
      common point-of-care test used in the cardiac catheterization lab to manage
      patient heparinization. Since the test has not been standardized, different
      systems frequently produce different results under the same clinical conditions.
      Duplicate paired ACT tests (n = 885) from 359 patients were performed on both
      instruments. Prothrombin times (PT) and activated partial thromboplastin times
      (aPTT) were also determined on subsets of these same samples (PT = 533; aPTT =
      487). The performance and relationships between the two tests were determined
      using a variety of statistical analytical techniques. The average difference
      between the ACT devices was only 8 sec, yet more than 60% of the measurements
      varied by more than 10%. Over one-fourth of measurements varied by more than 20%.
      The reproducibility to the HemoTec instrument was superior to the Hemochron
      instrument across the entire range of ACTs measured (mean coefficient of
      variation 2.4% +/- 3.1% vs. 7.2% +/- 6.1% for HemoTec and Hemochron,
      respectively; P < 0.00001; range = 65-555 sec). The relationship between the two
      ACTs was nonlinear. In therapeutic ranges used for interventional procedures (200
      350 sec), HemoTec and Hemochron ACTs are not comparable to one another.
      Statistical comparative analysis indicated that the HemoTec ACT has better
      overall performance.

PMID- 15864807
TI  - The truth about activated clotting time measurements.

PMID- 15864809
TI  - Optimization of human serum albumin production in methylotrophic yeast Pichia
      pastoris by repeated fed-batch fermentation.
AB  - An optimization method for repeated fed-batch fermentation was established with
      the aim of improving the recombinant human serum albumin (rHSA) production in
      Pichia pastoris. A simulation model for fed-batch fermentation was formulated and
      the optimal methanol-feeding policy calculated by dynamic programming method
      using five different methanol-feeding periods. The necessary state variables were
      collected from the calculated results and used for further optimization of
      repeated fed-batch fermentation. The optimal operation policy was investigated
      using the pre-collected state variables by estimating the overall profit per
      total methanol-feeding time. The calculated results indicated that the initial
      cell mass from the 2nd fed-batch fermentation on should be set at 35 or 40 g and
      methanol-feeding time at 264 h. In repeated fed-batch fermentation using the
      optimal operation policy, actual culture volume was in good agreement with the
      values simulated by model equations, but some discrepancy was observed in rHSA
      production. Minimum experiments were therefore carried out to re-evaluate rHSA
      production levels, which were then applied in re-calculations to determine the
      optimal operation policy. The optimal policy for repeated fed-batch fermentation
      established in the present study (i.e., 4-times-repeated fed-batch fermentation)
      achieved a 47% increase in annual rHSA production. Optimization of the culture
      period also brought about a 28% increase in annual rHSA production even in simple
      (not repeated) fed-batch fermentation.

PMID- 15864808
TI  - Endoplasmic reticulum stress induces the phosphorylation of small heat shock
      protein, Hsp27.
AB  - There are several reports describing participation of small heat shock proteins
      (sHsps) in cellular protein quality control. In this study, we estimated the
      endoplasmic reticulum (ER) stress-induced response of Hsp27 and alphaB-crystallin
      in mammalian cells. Treatment targeting the ER with tunicamycin or thapsigargin
      induced the phosphorylation of Hsp27 but not of alphaB-crystallin in U373 MG
      cells, increase being observed after 2-10 h and decline at 24 h. Similar
      phosphorylation of Hsp27 by ER stress was also observed with U251 MG and HeLa but
      not in COS cells and could be blocked using SB203580, an inhibitor of p38 MAP
      kinase. Other protein kinase inhibitors, like Go6983, PD98059, and SP600125,
      inhibitors of protein kinase C (PKC), p44/42 MAP kinase, and JNK, respectively,
      were without major influence. Prolonged treatment with tunicamycin but not
      thapsigargin for 48 h caused the second induction of the phosphorylation of Hsp27
      in U251 MG cells. Under these conditions, the intense perinuclear staining of
      Hsp27, with some features of aggresomes, was observed in 10%-20% of the cells.

PMID- 15864810
TI  - Roles of CTPL/Sfxn3 and Sfxn family members in pancreatic islet.
AB  - Pancreatic AR42J cells have the feature of pluripotency of the precursor cells of
      the gut endoderm. Betacellulin (BTC) and activin A (Act) convert them into
      insulin-secreting cells. Using mRNA differential display techniques, we have
      identified a novel mitochondrial transporter, which is highly expressed during
      the course of differentiation, and have designated it citrate transporter protein
      like protein (CTPL). Recently sideroflexin 1 (Sfxn1) was shown to be a
      susceptible gene of flexed-tail (f/f) mice, and CTPL has turned out to be a rat
      orthologous protein of Sfxn3, a member of sideroflexin family. CTPL/Sfxn3 was
      targeted to mitochondrial membrane like Sfxn1. The expression levels of
      CTPL/Sfxn3, Sfxn2, and Sfxn5 were upregulated in the early phase of
      differentiation into insulin-secreting cells but the expression levels of Sfxn1
      and Sfxn3 did not change. All Sfxn family members were expressed in rat
      pancreatic islet. The expression levels of CTPL/Sfxn3, Sfxn2, and Sfxn5 were also
      upregulated in islets of streptozotocin-induced diabetic rats compared to normal
      rats. The downregulation of CTPL/Sfxn3 in a rat insulinoma cell line, INS-1, with
      the antisense oligonucleotide did not affect the insulin secretion. Taken
      together, CTPL/Sfxn3 and some other family members might be important in the
      differentiation of pancreatic beta-cells as a channel or a carrier molecule and
      be related to the regeneration of pancreatic endocrine cells.

PMID- 15864812
TI  - Coxsackievirus and adenovirus receptor is essential for cardiomyocyte
      development.
AB  - The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein that
      is known to be a site of viral attachment and entry, but its physiologic
      functions are undefined. CAR expression is maximal in neonates and wanes rapidly
      after birth in organs such as heart, muscle, and brain, suggesting that CAR plays
      a role in the development of these tissues. Here, we show that CAR deficiency
      resulted in an embryonic lethal condition associated with cardiac defects.
      Specifically, commencing approximately 10.5 days postconception (dpc), CAR-/-
      cardiomyocytes exhibited regional apoptosis evidenced by both histopathologic
      features of cell death and positive staining for the apoptotic marker cleaved
      caspase 3. CAR-/- fetuses invariably suffered from degeneration of the myocardial
      wall and thoracic hemorrhaging, leading to death by 11.5 dpc. These findings are
      consistent with the view that CAR provides positive survival signals to
      cardiomyocytes that are essential for normal heart development.

PMID- 15864811
TI  - Regulation of Tbx6 expression by Notch signaling.
AB  - Somites are the first overt sign of segmentation in the vertebrate embryo and
      form from bilateral strips of paraxial mesoderm. Paraxial mesoderm arises from
      the primitive streak; it then migrates laterally and comes to lie on both sides
      of the neural tube. In the mouse, the T-box transcription factor Tbx6 is required
      for both somite formation and patterning. Tbx6 expression corresponds both
      temporally and spatially to somite formation, with expression in the primitive
      streak and presomitic mesoderm. Its expression in the latter could simply be
      explained by maintenance following its initial activation in the primitive
      streak. Alternatively, its expression in the presomitic mesoderm may be
      contributed by separate regulatory elements possibly under the control of
      different signals. We have begun to investigate how Tbx6 expression is controlled
      during development using a transgenic approach to identify the cis-acting
      regulatory regions. We show that it is possible to separate an element required
      for presomitic mesoderm expression from that driving expression in the primitive
      streak. Further, we show that a binding site for the Notch transcription factor
      RBP-Jkappa is necessary for Tbx6 presomitic mesoderm enhancer activity,
      indicating that Notch signaling is upstream of Tbx6 in the pathway directing
      somite formation and patterning.

PMID- 15864813
TI  - Y-chromosome and mitochondrial DNA studies on the population structure of the
      Christmas Island community.
AB  - Christmas Island is a remote Australian territory located close to the main
      Indonesian island of Java. Y-chromosome and mitochondrial DNA (mtDNA) markers
      were used to investigate the genetic structure of the population, which comprises
      communities of mixed ethnic origin. Analysis of 12 Y-chromosome biallelic
      polymorphisms revealed a high level of gene diversity and haplotype frequencies
      that were consistent with source populations in southern China and Southeast
      Asia. mtDNA hypervariable segment I (HVS-I) sequences displayed high levels of
      haplotype diversity and nucleotide diversity that were comparable to various
      Asian populations. Genetic distances revealed extremely low mtDNA differentiation
      among Christmas Islanders and Asian populations. This was supported by the
      relatively high proportion of sequence types shared among these populations. The
      most common mtDNA haplogroups were M* and B, followed by D and F, which are
      prevalent in East/Southeast Asia. Christmas Islanders of European descent were
      characterized by the Eurasian haplogroup R*, and a limited degree of admixture
      was observed. In general, analysis of the genetic data indicated population
      affinities to southern Chinese (in particular from the Yunnan Province) and
      Southeast Asia (Thailand, Malaysia, and Cambodia), which was consistent with
      historical records of settlement. The combined use of these different marker
      systems provides a useful and appropriate model for the study of contemporary
      populations derived from different ethnic origins.

PMID- 15864814
TI  - Abdominal obesity, insulin resistance, and colon carcinogenesis are increased in
      mutant mice lacking gastrin gene expression.
AB  - BACKGROUND: The authors recently reported that gastrin gene knockout (GAS-KO)
      mice had an increased risk for colon carcinogenesis in response to azoxymethane
      (AOM) compared with their wild type (WT) littermates. In the current report, the
      authors discuss the predisposition of GAS-KO mice to develop obesity and
      metabolic hormonal changes that may contribute to their increased risk of colon
      carcinogenesis. METHODS: The weight and deposition of fat was monitored in the
      mice over a 14 month period, using magnetic resonance imaging and nuclear
      magnetic resonance techniques. Changes in plasma concentrations of ghrelin,
      leptin, insulin, and glucose were assessed using radioimmunoassay analysis and
      enzyme-linked immunosorbent assays. Preneoplastic markers of colon carcinogenesis
      (aberrant crypt foci [ACFs]), in response to AOM, were measured in a subset of
      obese versus lean GAS-KO mice and were compared with the markers in WT mice.
      RESULTS: Increases in visceral adiposity were evident by age 2 months in GAS-KO
      mice, resulting in macroscopic obesity by age 7 months. Hyperinsulinemia and
      insulin:glucose ratios were increased significantly in GAS-KO mice as young as 1
      month and preceded alterations in nonfasting leptin and ghrelin levels. The
      number of ACFs per mouse colon were increased significantly in the following
      order: obese GAS-KO mice > lean GAS-KO mice > WT mice. Fasting plasma insulin
      levels were 0.88 +/- 0.1 ng/mL, 1.45 +/- 0.3, and 2.76 +/- 0.9 ng/mL in the WT,
      GAS-KO lean, and GAS-KO obese mice, respectively. CONCLUSIONS: The current
      results suggest the novel possibility that loss of amidated gastrins may increase
      adipogenesis, hyperinsulinemia, and colon carcinogenesis in GAS-KO mice. The
      increase in colon carcinogenesis may be due in part to hyperinsulinemia,
      increased obesity, and other associated hormone changes that were measured in GAS
      KO mice.

PMID- 15864815
TI  - The effect of cyclization on the enzymatic degradation of herpes simplex virus
      glycoprotein D derived epitope peptide.
AB  - One linear and three cyclic peptides corresponding to the 278-287
      ((278)LLEDPVGTVA(287)) sequence of glycoprotein D (gD-1) of herpes simplex virus
      were synthesized for the analysis of the effect of cyclization on protection
      against enzymatic degradation. In this design, the turn-forming motif
      ((281)DPVG(284)) was positioned in the central part of the peptide and elongated
      by three amino acids at both termini. Cyclopeptide formation was achieved by the
      introduction of a peptide bond, a disulfide bridge or a thioether link. The
      stability of these peptides was compared in human serum and also in rat lysosomal
      preparations. The data obtained in 10% and 50% human serum show that all three
      types of cyclization enhanced the stability, but at different levels. Complete
      stability was only achieved by the introduction of a thioether link, while the
      presence of a disulfide or peptide bond resulted in improved, but partial
      resistance against hydrolytic decomposition. In lysosomal preparations the
      presence of cyclic primary structure provided full protection against enzymatic
      hydrolysis. Taken together, these findings indicate that by appropriate
      structural modification it is feasible to construct a synthetic antigen with high
      stability against enzymatic degradation in complex biological fluids. Further
      studies are in progress to identify enzymes responsible for degradation in
      diluted human sera as well as in the lysosomal preparations and to gain more
      detailed information on the mechanism of action.

PMID- 15864816
TI  - Somatotopic blocking of sensation with navigated transcranial magnetic
      stimulation of the primary somatosensory cortex.
AB  - We demonstrate that spatially accurate and selective stimulation is crucial when
      cortical functions are studied by the creation of temporary lesions with
      transcranial magnetic stimulation (TMS). Previously, the interpretation of the
      TMS results has been hampered by inaccurate knowledge of the site and strength of
      the induced electric current in the brain. With a Navigated Brain Stimulation
      (NBS) system, which provides real-time magnetic resonance image (MRI)-guided
      targeting of the TMS-induced electric field, we found that TMS of a spatially
      restricted cortical S1 thenar area is sufficient to abolish sensation from a weak
      electric stimulation of the corresponding skin area. We demonstrate that with
      real-time navigation, TMS can be repeatably directed at millimeter-level
      precision to a target area defined on the MRI. The stimulation effect was
      temporally and spatially specific: the greatest inhibition of sensation occurred
      when TMS was applied 20 ms after the cutaneous test stimulus and the TMS effect
      was sensitive to 8-13 mm displacements of the induced electric field pattern. The
      results also indicate that TMS selectively to S1 is sufficient to abolish
      perception of cutaneous stimulation of the corresponding skin area.

PMID- 15864818
TI  - Tautomerism and 1H, 13C and 15N NMR spectral assignments of some nitro
      derivatives of malonic acid diamide.
AB  - Because of its reactivity, malonic acid diamide (1) was initially identified as
      an alternative precursor for the development of a new class of high-density
      insensitive energetic materials possessing low sensitivity to thermal
      decomposition and detonation by impact. Nitration of 1 was studied under
      different conditions and led to three different tautomeric forms (2-4) of
      nitromalonic acid diamine. Using stronger oxidation conditions the oxadiazole 5
      was generated in one step. We report the full 1H, 13C and 15N NMR structural
      characterization of these compounds in DMSO together with thermal, infrared, mass
      spectrometric and x-ray analysis. Experimental data obtained for 4 are compatible
      with an enol-imine form. Our interpretation is consistent with calculated 1H and
      13C NMR spectra (ACD).

PMID- 15864819
TI  - Concerning the origin of 19F-19F NMR COSY and NOESY connections in the spectra of
      perfluorooctanoic acid, R(F)-palmitic acid-F13 and diethyl perfluorosuberate.
AB  - A combination of 19F nuclear Overhauser effects (NOE) and molecular mechanics
      calculations are presented for delineating the spatial origin of the well-known
      four-bond 19F-19F COSY connections which are generally observed in the 19F NMR
      spectra of compounds containing perfluorinated chains. Perfluorooctanoic acid
      (PFOA), R(F)-palmitic acid-F13 and diethyl perfluorosuberate were used as test
      cases. Spin-lattice relaxation times (T1) are included and NOESY correlations
      through three and four bonds occur.

PMID- 15864820
TI  - Alcohol and cognitive function in older women.

PMID- 15864821
TI  - Alcohol and cognitive function in older women.

PMID- 15864822
TI  - Therapy for colorectal cancer.

PMID- 15864823
TI  - Therapy for colorectal cancer.

PMID- 15864824
TI  - Therapy for colorectal cancer.

PMID- 15864825
TI  - Insulin analogues.

PMID- 15864826
TI  - Insulin analogues.

PMID- 15864827
TI  - Jamie Oliver for Chief Medical Officer?

PMID- 15864828
TI  - Drug-induced bullous pemphigoid with positive patch test and in vitro IgE
      sensitization.

PMID- 15864829
TI  - Birt-Hogg-Dube syndrome: germline mutation in the (C)8 mononucleotide tract of
      the BHD gene in a German patient.

PMID- 15864830
TI  - What causes lesions in sperm whale bones?

PMID- 15864831
TI  - What causes lesions in sperm whale bones?

PMID- 15864832
TI  - Merits of a new drug trial for ALS?

PMID- 15864833
TI  - Bibliography. Current world literature. Valvular heart disease.

PMID- 15864834
TI  - Bibliography. Current world literature. Heart transplantation.

PMID- 15864836
TI  - Alternative treatments. Dealing with chronic pain.

PMID- 15864835
TI  - J. Donald M. Gass.

PMID- 15864837
TI  - Health tips. Sensitive teeth.

PMID- 15864838
TI  - Treatment counters low blood pressure upon standing.

PMID- 15864839
TI  - Cardiac PET scans. Sometimes, a clearer answer.

PMID- 15864840
TI  - Achilles rupture. Tending to tendon health.

PMID- 15864841
TI  - I understood that trans fat should be avoided because it can increase your risk
      of cardiovascular disease. And I had heard that the main source of trans fat is
      partially hydrogenated oils. Now, I see some products contain partially
      hydrogenated vegetable oils but still claim to be trans-fat free. How is this
      possible?

PMID- 15864842
TI  - Multislice CT cholangiography using thin-slab minimum intensity projection and
      multiplanar reformation in the evaluation of patients with suspected biliary
      obstruction: preliminary experience.
AB  - Thirty-three patients with suspected biliary obstruction were prospectively
      evaluated with multislice CT cholangiography using thin-slab minimum intensity
      projection (MinIP) and multiplanar reformation (MPR) to determine its usefulness
      and to compare with the comparative studies of endoscopic retrograde
      cholangiography (ERC), magnetic resonance cholangiography (MRC), or percutaneous
      transhepatic cholangiography (PTC). CT cholangiography made correct diagnoses in
      all biliary obstructions except in two patients with common bile duct stones. The
      correspondence with the comparative study was 93.9%. Multislice CT
      cholangiography may be favorable in noninvasive evaluation of biliary
      obstructions.

PMID- 15864844
TI  - Suicide in respect of forensic medicine. Proceedings of the 12th International
      Meeting on Forensic Medicine. May 29-31, 2003. Alpe Adria Pannonia, Rogaska
      Slatina, Slovenia.

PMID- 15864843
TI  - Proceedings of the 7th Meeting of the Immunology of Diabetes Society (IDS). March
      28-31, 2004. Cambridge, United Kingdom.

PMID- 15864845
TI  - Proceedings of the Second Joint European/North American Symposium on Congenital
      Heart Disease in the Adult. Held in honor of Professor Joseph K. Perloff.
      September 19-20, 2003. Santorini, Greece.

PMID- 15864846
TI  - Proceedings of the Foundation Anniversary Meeting and 25th Annual Meeting of the
      Spanish Society of Paediatric Endocrinology. June 19-21, 2003. Zaragoza, Spain.

PMID- 15864847
TI  - Festschrift on the occasion of the 70th birthday of Allan S. Hoffman. Gels,
      genes, grafts and giants: Part 5. Symposium in Maui, Hawaii, USA, December 2002.

PMID- 15864849
TI  - Hopes rise over Pasteur crisis.

PMID- 15864848
TI  - Worries over bioterrorism push.

PMID- 15864850
TI  - Bill McGinnis.

PMID- 15864851
TI  - The public's health and the law in the 21st Century. Proceedings of the Third
      Annual Partnership Conference on Public Health Law. June 14-16, 2004. Atlanta,
      Georgia, USA.

PMID- 15864852
TI  - Climate pressures.

PMID- 15864853
TI  - Peptide vaccine for leukemia.

PMID- 15864854
TI  - Two new agents effective in Gleevec-resistant CML.

PMID- 15864855
TI  - Linking socio-economic factors, environment and land cover in the German
      Highlands, 1945-1999.
AB  - Land-cover changes are caused by human activities and natural ecological
      processes. Thus, our study uses an interdisciplinary approach to research land
      cover changes. We present a method to (i) link socio-economic/environmental
      factors and land-cover changes, (ii) identify indicators of land-cover changes,
      and (iii) distinguish between socio-economic and environmental indicators
      associated with local types of overall land-cover changes. The study was
      conducted in the Lahn-Dill Highlands, Germany, a typical marginal rural
      landscape. In this region, we investigated land-cover changes occurring over the
      period 1945-1999. Land-cover data were derived from multi-temporal aerial
      photographs. Types of overall land-cover changes characterising the districts
      within the study area were differentiated. With the help of redundancy analysis
      (RDA), we analysed the relationships between land-cover changes and widely
      available socio-economic/environmental factors. The results reveal that both
      individual land-cover changes at patch level and types of overall land-cover
      changes characterising districts are correlated with socio-economic and
      environmental factors. Whereas the stable environmental factors are drivers of
      land-cover changes in our rural study area, socio-economic factors introduced
      into the analysis mostly result from land-cover changes. We identified
      correlative socio-economic indicators that cannot explain land-cover changes, but
      that in combination with the environmental factors can be used to greatly
      facilitate the reconstruction of past land-cover changes and thus lead to a
      better knowledge of land-cover history. Based on the types of overall land-cover
      changes, the results of the study can be adopted for the study of land-cover
      changes in other regions.

PMID- 15864856
TI  - International and comparative health law and ethics: a 25-year retrospective as a
      tribute to Professor Bernard Dickens.

PMID- 15864857
TI  - Recent Advances in Steroid Research. Proceedings of the 2004 G.J. Schroepfer Jr.
      Memorial Sterol Symposium. May 2004, Cincinnati, Ohio, USA.

PMID- 15864858
TI  - Sir John Vivian Dacie.

PMID- 15864860
TI  - [Proceedings and abstracts of the XIX Annual Meeting of Applied Research in
      Chagas Disease and the VII Annual Meeting of Applied Research in Leishmaniasis.
      Uberaba, Brazil, 24-26 October 2003].

PMID- 15864859
TI  - "God's dominion" and the wrongness of killing.

PMID- 15864861
TI  - [Management of severe sepsis. Proceedings of a resuscitation expert conference,
      December 3, 2002].

PMID- 15864862
TI  - Current awareness on yeast.

PMID- 15864863
TI  - [Hemodiafiltration and innovations for dialysis therapy. Proceedings of a
      meeting. Italy, 25-27 March 2004].

PMID- 15864865
TI  - Molecular Approaches to Osteoarthritis Research. Abstracts of the Kennedy
      Institute of Rheumatology Symposium, London, United Kingdom, April 18-20, 2004.

PMID- 15864864
TI  - [Androgen deficiency associated with age and male aging. Proceedings of the
      French Association of Urology 2004 Congress].

PMID- 15864866
TI  - [Abstracts of the 78th Annual Meeting of Japan Society of Occupational Health.
      April 2005, Tokyo, Japan].

PMID- 15864867
TI  - [Abstracts of the XXIX Francophone Meeting of Digestive Pathology. 2-6 April
      2005, Paris, France].

PMID- 15864868
TI  - Feasibility study for the development of certified reference materials for
      specific migration testing. Part 2: estimation of diffusion parameters and
      comparison of experimental and predicted data.
AB  - This paper describes the second part of a project whose main objective was to
      develop the know-how to produce certified reference materials (CRMs) for specific
      migration testing. Certification parameters discussed are the diffusion
      coefficient, D(P), the respective polymer-specific coefficient, A(P), of the
      migrant polymer combinations and the partitioning coefficient, K(P,F), describing
      the partitioning of the migrant between the polymer and a food simulant. The
      parameters were determined for 16 preliminary candidate CRMs. Each parameter was
      determined by one laboratory. The six materials most suitable as reference
      materials were selected and the parameters then determined by four laboratories.
      The coefficients resulting from this small-scale interlaboratory comparison study
      can be regarded as the most reliable values available to date. These coefficients
      were applied for a comparison of experimental and predicted migration data. The
      experimental migration data arose from the same project and were determined by
      one laboratory for the first 16 materials and subsequently by four laboratories
      for the six materials selected in the second phase. Overall, experimental and
      predicted migration data fit together quite well. Roughly half of the predicted
      data were within +/-10%; almost all predicted data were within +/-40% compared
      with the experimental data.

PMID- 15864869
TI  - Demystifying ministry leadership formation.

PMID- 15864870
TI  - Leadership communication: building a stronger culture of trust and results
      through business ethics based on an IRB-approved research study.

PMID- 15864871
TI  - Informed consent: a cautionary tale.

PMID- 15864872
TI  - Multicenter study of hyaluronic acid obtained by biotechnology to evaluate
      clinical efficacy and safety in knee osteoarthritis.
AB  - Viscosuppplementation with intra-articular hyaluronic acid (hyaluronan [HA]) is a
      relatively new option for improving pain and articular function in patients with
      symptomatic knee osteoarthritis. An open multi-center study was performed in 365
      patients with definite and symptomatic knee osteoarthritis from seven Latin
      American countries. Five doses of HA were administered once a week. The
      parameters studied were pain (six items), stiffness (two items) and functional
      capacity (17 items). The parameters were evaluated 1 week after the corresponding
      injection. Statistical differences were found when basal determinations of the
      three parameters were compared with the results of the first and fourth
      administration (p < 0.05). Intra-articular HA administration was well tolerated.
      Treatment-related nonserious adverse events were registered in 2.5% of
      administrations. Based on the results obtained, HA is a useful and well-tolerated
      symptomatic treatment for knee osteoarthritis with a rapid onset of action.

PMID- 15864873
TI  - Early and late effect of infliximab on circulating dendritic cells phenotype in
      rheumatoid arthritis patients.
AB  - The aim of this study was to analyze the phenotype of circulating dendritic cells
      (DCc) in rheumatoid arthritis (RA) patients before and after treatment with
      infliximab (at 24 h and 6 months) and the correlation between these changes and
      the clinical response to treatment. Sixteen patients with RA were recruited and
      clinical status was determined using the Disease Activity Score 28 (DAS28). All
      patients had active disease (mean DAS28 = 5.96) and were suitable for treatment
      with infliximab. Samples of peripheral venous blood were obtained before
      administration of the first dose of infliximab and again at 24 h and 6 months
      after treatment. DCc populations were analyzed by flow cytometry. At 24 h, there
      were no differences in the clinical status of the patients. However, we found a
      decrease in CD11c+ and, to a lesser extent, CD123+ DCc percentages. The
      expression of CD83, the most important activation marker for DC, was also shown
      to be decreased 24 h after infliximab therapy. After 6 months of treatment, all
      patients showed significant clinical improvement (mean DAS28 = 3.64, p < 0.001)
      and expression of the activation marker on DCc remained low. In conclusion, this
      study supports the role of tumor necrosis factor (TNF)-alpha blockade in
      preventing the maturation of DCc and in reducing the expression of their
      activation markers. Although the clinical response to infliximab was not observed
      after 24 h, DCc activation was strongly reduced by anti-TNF-alpha therapy. After
      6 months of treatment, current data show a less active phenotype of DCc
      associated with clinical improvement in all patients in the study.

PMID- 15864874
TI  - Treatment with oral biphosphonates can increase the sensitivity of sestamibi
      radionuclide imaging in patients with primary hyperparathyroidism.
AB  - The sensitivity of 99mTc-sestamibi scan in detecting parathyroid disease in
      primary hyperparathyroidism (PHP) is almost 90%, and therefore facilitates
      successful parathyroidectomy. To enhance the diagnostic accuracy of the
      procedure, we repeated imaging with 99mTc-sestamibi in 15 patients with PHP and
      an initially negative (11 patients) or weakly positive (four patients) 99mTc
      sestamibi scan after the administration of 10 mg of oral alendronate for 2
      months. Serum calcium, phosphate and parathormone (PTH) measurements were
      obtained at presentation and after 1 and 2 months' treatment with alendronate.
      Eight patients with an initially negative 99mTc-sestamibi scan demonstrated at
      least one area of uptake in the repeated scan. Six of these patients underwent
      surgery and obtained a biochemical cure; a single adenoma was found in four and
      hyperplasia in the remaining two. In all four patients with an initially weakly
      positive 99mTc-sestamibi scan, the repeated scan demonstrated enhanced uptake and
      also revealed further areas of uptake. Two of these patients underwent surgery
      with a biochemical cure; an adenoma was found in one and hyperplasia in another.
      Compared with baseline there was a significant increase in PTH but not in calcium
      or phosphate levels during treatment with alendronate. We suggest that, in
      patients with PHP and a negative or weakly positive initial 99mTc-sestamibi scan,
      administration of oral alendronate may be associated with a positive repeated
      99mTc-sestamibi scan and can thus enhance the sensitivity of the procedure.

PMID- 15864875
TI  - Telmisartan has the strongest binding affinity to angiotensin II type 1 receptor:
      comparison with other angiotensin II type 1 receptor blockers.
AB  - There is a growing body of evidence that the renin-angiotensin system (RAS) plays
      a pivotal role in the pathogenesis of cardiovascular diseases. Indeed, large
      clinical trials have demonstrated a substantial benefit of the blockade of this
      system for cardiovascular-organ protection. Although several types of angiotensin
      II type 1 (AT1) receptor blockers (ARBs) are commercially available for the
      treatment of patients with hypertension, comparisons of the binding affinity to
      AT1 receptor among them remain to be elucidated. In this study, we examined the
      dissociation rate of several ARBs from AT1 receptor in vitro. Angiotensin II time
      dependently dissociated telmisartan, olmesartan, candesartan, valsartan, losartan
      and an active metabolite of losartan, EXP3174, from membrane components
      containing human AT1 receptor The dissociation rate constant of each ARB was
      0.003248, 0.004171, 0.005203, 0.009946, 0.01027 and 0.008561 min(-1), with
      corresponding half-lives of 213, 166, 133, 70, 67 and 81 min, respectively. These
      results demonstrate that telmisartan has the strongest binding affinity to AT1
      receptor among various ARBs examined herein. The rank order of affinity was
      telmisartan > olmesartan > candesartan > EXP3174 > or = valsartan > or =
      losartan. The present findings suggest that telmisartan (Micardis) may have long
      lasting blood pressure-lowering effects and superior cardioprotective properties
      in patients with hypertension due to its strongest AT1 receptor antagonistic
      ability.

PMID- 15864876
TI  - Histamine in chronic allergic responses.
AB  - In addition to its well-characterized effects in the acute inflammatory and
      allergic responses, histamine has been shown to affect chronic inflammation and
      regulate several essential events in the immune response. Histamine can
      selectively recruit the major effector cells into tissue sites and affect their
      maturation, activation, polarization, and effector functions leading to chronic
      inflammation. On the other hand histamine acting through its receptor (HR) type 2
      positively interferes with the peripheral antigen tolerance induced by T
      regulatory (Treg) cells in several pathways. Histamine also regulates antigen
      specific TH1 and TH2 cells, as well as related antibody isotype responses. These
      findings provide suitable explanation for the observations in the experimental
      model of asthma showing that allergic inflammatory responses and bronchial
      hyperresponsiveness may be susceptible to HR1 blockade. Apparently, the various
      effects of histamine on immune regulation are due to differential expression and
      regulation of 4 histamine receptors and their distinct intracellular signals. In
      addition, differences in affinities of these receptors is highly decisive on the
      biological effects of histamine and drugs that target histamine receptors. This
      article highlights novel discoveries in histamine immunobiology and discusses
      their relevance to the allergic inflammatory responses.

PMID- 15864877
TI  - Efficacy of sublingual allergen vaccination for respiratory allergy in children.
      Conclusions from one meta-analysis.
AB  - BACKGROUND: Sublingual route, that allows the safe administration of allergen
      vaccination at home and without injections, is a highly attractive alternative to
      parenteral delivery, especially among the youngest population. However, its
      efficacy in children has been questioned. OBJECTIVE: To evaluate the efficacy
      (symptom and medication scores) of sublingual allergen vaccination compared to
      placebo in paediatric patients. SEARCH STRATEGY: MEDLINE, EMBASE, ISI and the
      Cochrane Central Register of Controlled Trials were explored (completed in
      January/04) for potentially relevant studies. SELECTION CRITERIA: Randomized
      double-blind placebo-controlled clinical trials involving children < or = 14
      years-old with either rhinitis or asthma of proved allergic aetiology. Data
      collection and analysis. Two reviewers analyzed independently the eligibility of
      studies for inclusion. The combined standardized mean difference (SMD) method was
      used to evaluate differences. Since heterogeneity was expected, probably due to
      the different procedures from each trial, we used the random effect model to
      obtain SMD. However, we also present the SMD values from the fixed effect model.
      The main outcomes were clinical symptom (asthma, rhinitis and conjunctivitis) and
      drug requirement scores. Safety, immunological and clinical changes were also
      reviewed. RESULTS: Seven double-blind placebo-controlled trials, enrolling 256
      children (129 treatment and 127 placebo recipients), were analyzed. We observed
      decreases in symptom (SMD: -1.42 for asthma, -0.44 for rhinitis and -1.49 for
      conjunctivitis) and medication requirement (SMD: -1.01) scores. Only reductions
      in asthma (p=0.01) and drug dosage (p=0.06) scores reached statistical
      significance with the random effect model but changes in rhinitis symptoms
      (p=0.27) or conjunctival symptoms (p=0.19) were not statisticaly significant.
      Results obtained with the fixed effect model were similar in magnitude (SMD: 
      1.60 for asthma, SMD: -0.47 for rhinitis, SMD: -1.09 for conjunctivitis and, SMD:
      -0.54 for drug intake). Safety was a constant in all the studies; neither severe
      nor systemic reactions were observed and, oral and gastrointestinal complains
      were the most common adverse effects. CONCLUSION: In children, sublingual
      delivery of allergen vaccination constitutes a safe and effective alternative to
      the sublingual route to reduce allergy respiratory symptoms and drug intake.
      Further studies in this group of age are required to establish the optimal
      conditions for sublingual allergen vaccination.

PMID- 15864878
TI  - Specific IgG to Thermoactynomices vulgaris, Micropolyspora faeni and Aspergillus
      fumigatus in building workers exposed to esparto grass (plasterers) and in
      patients with esparto-induced hypersensitivity pneumonitis.
AB  - BACKGROUND: Esparto is one the most frequent causes of hypersensitivity
      pneumonitis in Spain. OBJECTIVE: Determination of risk factors in the working
      environment that could explain the sensitisation process, and assessment of the
      differences in specific IgG levels to Aspergillus fumigatus, Saccharopolyspora
      rectivirgula and Thermoactynomices vulgaris in patients with hypersensitivity
      pneumonitis induced by esparto, exposed healthy plasterers and control
      population. METHODS: Determination of precipitins and specific IgG to
      Aspergillusfumigatus, Saccharopolyspora rectivirgula and Thermoactynomices
      vulgaris in the three previously mentioned groups. Questionnaire on possible risk
      occupational and extra-occupational factors. RESULTS: Both healthy and exposed
      plasterers have higher levels of specific IgG to Aspergillus fumigatus,
      Saccharopolyspora rectivirgula and Thermoactynomices vulgaris than the healthy
      controls. The patients had higher levels of IgG than exposed healthy plasterers
      only to Thermoactynomices vulgaris. Precipitins were detected in only two
      patients. There were no occupational factors influencing on the sensitisation
      process. CONCLUSIONS: Specific IgG is an occupational exposure marker among
      plasterers, but it has not been possible to establish a cut off point that
      differentiates exposed subjects from affected ones. This determination has a
      greater sensitivity than precipitins. We did not identify occupational or extra
      occupational risk factors that facilitate the sensitisation process.

PMID- 15864879
TI  - Rupatadine 10 mg and cetirizine 10 mg in seasonal allergic rhinitis: a
      randomised, double-blind parallel study.
AB  - This randomised, double-blind, parallel-group, multicentre clinical trial
      evaluated the efficacy and safety of rupatadine, a new antihistamine with
      antiplatelet-activating factor (PAF) activity, and cetirizine in the treatment of
      patients with seasonal allergic rhinitis (SAR). A total 249 patients were
      randomised to receive rupatadine 10 mg once daily (127 patients) or cetirizine 10
      mg (122 patients) for two weeks. The main efficacy variable was the mean total
      daily symptom score (mTDSS) and was based on the daily subjective assessment of
      the severity of each rhinitis symptom--nasal (runny nose, sneezing, nasal itching
      and nasal obstruction) and non-nasal (conjunctival itching, tearing, and
      pharyngeal itching)--recorded by patients in their diaries. The mTDSS was 0.7 for
      both treatment groups (intention to treat analysis). In the investigator's global
      evaluation of efficacy at the seventh day, 93.3% and 83.7% patients in the
      rupatadine and cetirizine groups, respectively, showed some or great improvement
      (p = 0.022). In the per protocol analysis (n = 181), runny nose at the seventh
      day of treatment was absent or mild in 81.1% of patients in the rupatadine group
      and in 68.6% of patients in the cetirizine group (p = 0.029). In any case
      statistical significance was not maintained at the second week. Overall, all
      treatments were well tolerated. Adverse events (AEs) were similar in both
      treatment groups, i.e. headache, somnolence and fatigue/asthenia as the most
      often reported. Somnolence was reported in 9.6% and 8.5% of patients treated with
      rupatadine or cetirizine, respectively. The most reported AEs (67%) were mild in
      intensity. Our results suggest that rupatadine 10 mg may be a valuable and safe
      alternative for the symptomatic treatment of SAR.

PMID- 15864880
TI  - Skin tests with native, depigmented and glutaraldehyde polymerized allergen
      extracts.
AB  - INTRODUCTION: Dose-response skin prick tests are an important tool to standardise
      allergen extracts and to evaluate changes in skin test response as a consequence
      of allergen modifications. OBJECTIVES: To evaluate in vivo and in vitro
      characteristics of 3 different types of extracts of Phleumpratense, Olea
      europaea, Parietaria judaica and Dermatophagoides pteronyssinus. MATERIAL AND
      METHODS: Three types of extracts were used: native unmodified extracts (N),
      depigmented extracts (DP) (extracts subjected to a mild acid treatment under
      controlled conditions and dialysis), and a depigmented glutaraldehyde polymerised
      extract (DPP). Adult patients were skin tested in duplicate with the 3 types of
      extracts. The dose-response relationship between the geometric mean of the wheal
      areas and the allergen concentrations was calculated for each patient using
      regression line analysis. The amount of freeze-dried allergen preparation needed
      to produce the same wheal size as histamine was calculated in each patient
      (individual 10 HEP) and for each of the 3 types of extracts. In vitro analysis
      consisted of major allergen determinations and specific IgE and IgG inhibitions.
      RESULTS: The respective 10 HEP values for N, DP and DPP preparations were 0.20
      mg, 0.15 and 2.11 for D. pteronyssinus. For P. pratense, these values were 0.02
      mg, 0.02 and 0.99; for O. europaea 0.15, 0.44 and 4.9; and for P. judaica 0.01,
      0.008 and 1.78 mg. CONCLUSIONS: The polymerised depigmented extracts are
      significantly less allergenic than the corresponding native and depigmented
      extracts. This could provide a greater safety margin for the administration of
      higher doses of immunotherapy in a shorter period of time.

PMID- 15864881
TI  - Antigen specific quantification of sulfidoleukotrienes in patients allergic to
      Betalactam antibiotics.
AB  - BACKGROUND: After in vitro allergen-specific stimulation, basophils become
      activated and release sulfidoleukotrienes LTC4, LTD4 and LTE4. This can be
      detected by means of the CAST assay. We assessed the positivity criteria and the
      reliability of antigen-specific sulfidoleukotriene production (CAST) in the in
      vitro diagnosis of betalactam (BL) allergic patients. MATERIAL AND METHODS: We
      studied a sample of 67 patients (age 48.94 +/- 15.76 years) who had presented
      with anaphylaxis or urticaria-angioedema within the first 60 minutes after
      administration of Amoxicillin (54/67), Penicillin G (7/67), Cefuroxime (5/67) or
      Cefazoline (1/67). All of them had a positive skin test to at least one of the
      antigenic determinants of Penicillin. As control group 30 adults with negative
      skin tests who tolerated BL were included. All of them underwent skin tests, oral
      provocation tests, specific IgE (CAP-FEIA, Pharmacia) and CAST. RESULTS:
      Positivity criteria were established by means of ROC curves: a sLT release
      induced by Betalactams of at least 100 pg/ml and greater than or equal to 3 times
      the basal value. The overall sensitivity of CAST is 47.7% and specificity 83.3%.
      Sensitivity of specific IgE is 37.8% and specificity 83.3%. CONCLUSIONS: We have
      established validated positivity criteria for the CAST technique in patients
      allergic to Betalactams. This technique is a useful in vitro diagnostic method in
      patients with IgE-mediated allergy to Betalactam antibiotics.

PMID- 15864882
TI  - Serological prevalence of anti-latex IgE antibodies in unselected blood donors in
      Argentina.
AB  - The prevalence of specific IgE to natural rubber latex proteins in the general
      population remains uncertain. The purpose of this study was to determine the
      prevalence of sera containing specific IgE antibodies to latex proteins using
      immunoenzymatic methods. A population of 500 unselected adult voluntary blood
      donors was the source of the sera used in this study. Two different
      immunoenzymatic methods (EAST and CARLA) were used to analyze the presence of
      specific IgE antibodies. Confirmation assay was carried out by inhibition ELISA
      and immunoblotting. Sera from healthy nonatopic individuals were also used as
      control. Two hundred and twenty five sera showed higher than normal total IgE
      levels. Of those, three presented latex specific IgE antibodies, which could be
      inhibited in a dose-response manner with the natural rubber latex and glove
      extracts. Several latex allergens were recognized by the IgE antibodies from
      these positive sera. This low seroprevalence (0.66%) indicates that latex
      hypersensitivity is not an important problem in the general population. We
      believe that prevention of latex exposure is only necessary in high risk groups
      of patients.

PMID- 15864883
TI  - Pollen allergy in Cordoba city: frequency of sensitization and relation with
      antihistamine sales.
AB  - The occurrence of symptoms in pollen allergy patients in urban areas may be
      affected by local environmental factors such as sources of pollution, natural and
      ornamental vegetation, local architecture impeding dispersion, etc. The aim of
      this study was to analyse the frequency of sensitization in pollen allergy
      patients and the relationship with antihistamine sales. For this study, a large
      number of clinical records, together with pharmaceutical and pollen data, were
      collected between 1999 and 2001 in the city of Cordoba, in the south of the
      Iberian Peninsula. Differences were observed in the symptoms suffered by pollen
      allergy patients in different areas of the city due to varying local emission of
      both biological and non-biological particles. Temporal distribution of symptoms
      over the three study years was influenced by meteorological factors, especially
      rainfall patterns; higher water supply to plants was associated with increased
      airborne pollen concentrations. Air pollution might be one of the main factors
      affecting the distribution of pollen allergy patients within the city. Recent
      years have seen a worsening of symptoms and increased sensitization to urban
      species such as plane-trees.

PMID- 15864884
TI  - Bone mineral density in asthmatic patients using low dose inhaled
      glucocorticosteroids.
AB  - Inhaled glucocorticosteroids are clearly beneficial in subjects with moderate or
      severe asthma since they are well tolerated, reduce symptoms, and improve quality
      of life. Some studies suggest that inhaled glucocorticosteroids can adversely
      affect bone mineral density. The aim of this study is to determine the effects of
      inhaled glucocorticosteroid therapy on bone mineral density in female patients.
      Forty-five asthmatic female patients (36 premenopousal and 9 postmenopausal) and
      forty-six healthy control subjects were included in the study. Bone mineral
      density was measured from lumbar spine (L1-4) and femur (neck, trochanter, and
      Ward's triangle) by dual energy X-Ray absorptiometry. Age, occupation, menopause
      and smoking status, alcohol consumption, body mass index, previous fractures,
      family history of fractures, menstrual history, ooferectomy, number of
      pregnancies, the duration of lactation, physical activity and calcium intake were
      questioned according to the European Vertebral Osteoporosis Study Group (EVOS)
      form. Cumulative inhaled glucocorticosteroid dose was calculated. T score of
      femoral neck and T score and bone mineral density of Ward's triangle were
      significantly lower in asthmatic patients compared to control group but no
      statistically significant correlation was found between the disease duration,
      inhaled steroid treatment duration, cumulative inhaled dose and annual inhaled
      steroid dose and bone mineral density measurement. These results suggest that in
      asthmatic patients using low dose inhaled corticosteroids bone mineral density is
      lower than in healthy controls but it is still unclear if asthma by itself is a
      risk factor for osteoporosis.

PMID- 15864885
TI  - Allergen immunotherapy decreases specific allergen-induced expression of Fas and
      FasL on CD4+ and CD8+ cells.
AB  - Apoptosis programmed cell death without induction of an inflammatory response. It
      is mediated by Fas--a cell surface protein which is expressed on activated
      lymphocytes. Interaction with its counterpart--the Fas ligand induces the
      apoptosis of Fas bearing cells. The mechanism underlying successful immunotherapy
      has not been identified. The aim of this study was to investigate whether
      specific immunotherapy (SIT) might affect Fas and FasL expression after
      stimulation with specific allergen. The study was conducted on 8 allergic
      subjects and 8 healthy volunteers as controls. The allergic patients were treated
      with conventional SIT (Pollinex). Blood samples were collected before the first
      day and 7 days after the last injection. Isolated CD4+ and CD8+ cells were
      incubated in various concentrations of specific allergen (1, 10, 100 ng/ml) or in
      medium alone. Indirect immunofluorescence test with rabbit IgG against human Fas
      and FasL was performed. The percentage of positive cells was determined under
      fluorescence microscope. The expression of Fas and FasL before SIT was
      significantly increased on CD4+ and CD8+ cells under the influence of specific
      allergen (10, 100 ng/ml). After SIT, significant decrease in the expression of
      both molecules was observed, although elimination of allergen-reactive cells was
      not complete and their number was still higher than in the controls. CONCLUSION:
      The exposure of CD4+ and CD8+ cells on allergen may induce the Fas-FasL apoptotic
      pathway. Significant decrease in number of allergen-reactive CD4+, CD8+ cells
      after SIT suggests participation of the phenomenon in deletion of clones, which
      may be a part of the allergen tolerance mechanism achieved naturally or during
      SIT.

PMID- 15864886
TI  - IgA and/or IgG subclass deficiency in children with recurrent respiratory
      infections and its relationship with chronic pulmonary damage.
AB  - Most patients with IgA and/or IgG subclass deficiency are asymptomatic but some
      may suffer from frequent mainly respiratory infections. The aim of our study was
      to determine the frequency of IgA and/or IgG subclass deficiencies and the rate
      of chronic pulmonary damage secondary to recurrent pulmonary infections in these
      children. Serum IgA and IgG subclass levels were measured in 225 children aged 6
      months to 6 years with recurrent sinopulmonary infections (44 with recurrent
      upper respiratory tract infections, 100 with recurrent pulmonary infections and
      81 with recurrent bronchiolitis). In order to determine chronic pulmonary damage
      due to recurrent infections in patients with recurrent pulmonary infections CT
      scans of thorax were also obtained. The overall frequency of antibody defects was
      found to be 19.1%. IgA deficiency was observed in 9.3%, IgG subclass deficiency
      in 8.4% and IgA + IgG subclass deficiency in 1.4%. The prevalance of IgA and/or
      IgG subclass deficiency was 25% in patients with recurrent upper respiratory
      tract infections, 22% in patients with recurrent pulmonary infections and 12.3%
      in patients with recurrent bronchiolitis (p>0.05). Chronic pulmonary damage in
      lungs was determined radiologically in 17 of 100 cases with recurrent pulmonary
      infection. In IgG subclass deficiencies sequel changes, although not
      statistically significant, were observed five times more frequently than that of
      IgA deficiencies. CT scans revealed pulmonary sequels in 5 of the 22 (22.7%)
      patients with recurrent pulmonary infections and immunodeficiency (bronchiectasis
      in 2 patients with IgG3 deficiency, fibrotic changes in one with IgA deficiency
      and in one with IgG3 deficiency, bronchiolitis obliterans in one with IgG2 + IgG3
      deficiency). On the other hand, pulmonary sequels were observed in 12 patients
      (15.4%) with normal immunoglobulin levels. Eight of them were bronchiolitis
      obliterans, 2 of them were atelectasia and 1 of them was bronchiectasia. We
      therefore suggest that determination of antibody levels and evaluation of
      pulmonary alterations is crucial in patients with recurrent sinopulmonary
      infections since the deficiency of antibodies is associated with a greater
      pulmonary damage.

PMID- 15864887
TI  - Anaphylaxis produced by oxaliplatin.
AB  - We are discussing two patients, with clinically compatible reactions, who display
      an immediate hypersensitive mechanism following the administration of
      oxaliplatin, confirmed by the performance of cutaneous tests.

PMID- 15864888
TI  - Recurrent urticaria lesions in a heparin-allergic patient: most likely another
      form of "recall urticaria".
AB  - In this report we describe a female patient with a history of heparin allergy and
      recurrent urticaria lesions at definite locations where the heparin injections
      were administered previously.

PMID- 15864889
TI  - Occupational asthma caused by Ipe (Tabebuia spp) dust.
AB  - BACKGROUND: Ipe is a resistant hardwood that contains naphtoquinones. It is
      easily found and frequently used in South and Central America. Naphtoquinones are
      skin sensitizers. OBJECTIVE: To describe a case of occupational asthma related to
      Ipe wood dust. METHODS: The patient was submitted to a clinical evaluation
      consisting of a respiratory symptom questionnaire, occupational history, serial
      measurements of lung function by spirometry, skin prick tests, patch tests,
      specific IgE and specific bronchial provocation tests to Ipe dust. RESULTS:
      Serial lung function measurements showed sustained regression of obstruction
      following removal from exposure. Skin prick tests, but not patch tests, were
      positive to Ipe, and a specific bronchial challenge showed a late asthmatic
      reaction. Specific IgE search was negative. CONCLUSIONS: Exposure to Ipe wood
      dust can lead to occupational asthma. The underlying mechanism should be
      investigated.

PMID- 15864890
TI  - Newborn screening for cystic fibrosis: recommendations from the Centers for
      Disease Control and Prevention.

PMID- 15864891
TI  - Benefit vs. harm of treatment of chronic hepatitis C.

PMID- 15864892
TI  - Treating children with obstructive sleep apnea.

PMID- 15864893
TI  - Evaluation of chronic dyspnea.
AB  - Chronic dyspnea is defined as dyspnea lasting more than one month. In
      approximately two thirds of patients presenting with dyspnea, the underlying
      cause is cardiopulmonary disease. Establishing an accurate diagnosis is essential
      because treatment differs depending on the underlying condition. Asthma,
      congestive heart failure, chronic obstructive pulmonary disease, pneumonia,
      cardiac ischemia, interstitial lung disease, and psychogenic causes account for
      85 percent of patients with this principal symptom. The history and physical
      examination should guide selection of initial diagnostic tests such as
      electrocardiogram, chest radiograph, pulse oximetry, spirometry, complete blood
      count, and metabolic panel. If these are inconclusive, additional testing is
      indicated. Formal pulmonary function testing may be needed to establish a
      diagnosis of asthma, chronic obstructive pulmonary disease, or interstitial lung
      disease. High-resolution computed tomography is particularly useful for
      diagnosing interstitial lung disease, idiopathic pulmonary fibrosis,
      bronchiectasis, or pulmonary embolism. Echocardiography and brain natriuretic
      peptide levels help establish a diagnosis of congestive heart failure. If the
      diagnosis remains unclear, additional tests may be required. These include
      ventilation perfusion scans, Holter monitoring, cardiac catheterization,
      esophageal pH monitoring, lung biopsy, and cardiopulmonary exercise testing.

PMID- 15864894
TI  - Information from your family doctor. Why am I short of breath?

PMID- 15864895
TI  - Iliotibial band syndrome: a common source of knee pain.
AB  - Iliotibial band syndrome is a common knee injury. The most common symptom is
      lateral knee pain caused by inflammation of the distal portion of the iliotibial
      band. The iliotibial band is a thick band of fascia that crosses the hip joint
      and extends distally to insert on the patella, tibia, and biceps femoris tendon.
      In some athletes, repetitive flexion and extension of the knee causes the distal
      iliotibial band to become irritated and inflamed resulting in diffuse lateral
      knee pain. Iliotibial band syndrome can cause significant morbidity and lead to
      cessation of exercise. Although iliotibial band syndrome is easily diagnosed
      clinically, it can be extremely challenging to treat. Treatment requires active
      patient participation and compliance with activity modification. Most patients
      respond to conservative treatment involving stretching of the iliotibial band,
      strengthening of the gluteus medius, and altering training regimens.
      Corticosteroid injections should be considered if visible swelling or pain with
      ambulation persists for more than three days after initiating treatment. A small
      percentage of patients are refractory to conservative treatment and may require
      surgical release of the iliotibial band.

PMID- 15864896
TI  - Evidence-based prenatal care: part II. Third-trimester care and prevention of
      infectious diseases.
AB  - All pregnant women should be offered screening for asymptomatic bacteriuria,
      syphilis, rubella, and hepatitis B and human immunodeficiency virus infection
      early in pregnancy. Women at increased risk should be tested for hepatitis C
      infection, gonorrhea, and chlamydia. All women should be questioned about their
      history of chickenpox and genital or orolabial herpes. Routine screening for
      bacterial vaginosis is not recommended. Influenza vaccination is recommended in
      women who will be in their second or third trimester of pregnancy during flu
      season. Women should be offered vaginorectal culture screening for group B
      streptococcal infection at 35 to 37 weeks' gestation. Colonized women and women
      with a history of group B streptococcal bacteriuria should be offered intrapartum
      intravenous antibiotics. Screening for gestational diabetes remains
      controversial. Women should be offered labor induction after 41 weeks' gestation.

PMID- 15864897
TI  - Information from your family doctor. Infections during pregnancy: what you should
      know.

PMID- 15864898
TI  - Indications and recommendations for pacemaker therapy.
AB  - Each year, pacemaker therapy is prescribed to approximately 900,000 persons
      worldwide. Current pacemaker devices treat bradyarrhythmias and tachyarrhythmias
      and, in some cases, are combined with implantable defibrillators. In older
      patients, devices that maintain synchrony between atria and ventricles are
      preferred because they maintain the increased contribution of atrial contraction
      to ventricular filling necessary in this age group. In general, rate-responsive
      devices are preferred because they more closely simulate the physiologic function
      of the sinus node. Permanent pacemakers are implanted in adults primarily for the
      treatment of sinus node dysfunction, acquired atrioventricular block, and certain
      fascicular blocks. They also are effective in the prevention and treatment of
      certain tachyarrhythmias and forms of neurocardiogenic syncope. Biventricular
      pacing (resynchronization therapy) recently has been shown to be an effective
      treatment for advanced heart failure in patients with major intraventricular
      conduction effects, predominately left bundle branch block. Many studies have
      documented that pacemaker therapy can reduce symptoms, improve quality of life
      and, in certain patient populations, improve survival.

PMID- 15864899
TI  - Diagnosing rotator cuff tears.

PMID- 15864900
TI  - A newborn with an umbilical mass.

PMID- 15864901
TI  - Use of routinely collected occupational exposure data in register-based studies-
      a trade off between feasibility and misclassification.

PMID- 15864902
TI  - Indicators of mancozeb exposure in relation to thyroid cancer and neural tube
      defects in farmers' families.
AB  - OBJECTIVES: The fungicide mancozeb has been suspected of causing thyroid cancer
      and neural tube defects. The aim of the study was to investigate associations of
      indicators of mancozeb exposure with thyroid cancer and neural tube defects in
      farmers' families. METHODS: National registers in Norway, identifying 105 403
      female and 131 243 male farmers, born in 1925-1971, and their 300 805 children
      available for analyses, born in 1952-1991, were cross-linked with national
      agricultural censuses, 1969-1989, and the population register. Neural tube
      defects (ICD-8 740-742) at birth among the 102 703 children conceived between May
      1973 and April 1991 were identified in the medical birth register. Likewise
      thyroid cancer (ICD-7 194) was identified in the cancer register through 2000.
      Data on farm production and fungal forecasts (humid and temperate weather
      conditions) in 1973-1990, obtained from agricultural censuses and meteorological
      measurement stations, respectively, served as the mancozeb exposure indicators.
      The adjusted rate ratio or prevalence ratio (PR) estimates with 95% confidence
      intervals (95% CI) were computed in a Poisson regression analysis. RESULTS:
      Neural tube defects (131 cases, prevalence 12.8/10 000 births) was moderately
      associated with potato cultivation (PR 1.6, 95% CI 1.1-2.3) and paternal work of
      > 500 hours/year (PR 1.6, 95% CI 1.1-2.5). Altogether 319 thyroid cancer cases
      were identified: 141 in female farmers (incidence 10.2/100 000 person-years), 79
      in male farmers (incidence 3.2/100 000 person-years), and 99 in offspring (female
      and male incidence 3.4 and 0.6/100 000 person-years, respectively). Mancozeb
      exposure was not associated with thyroid cancer. CONCLUSIONS: A moderate
      association seems to exist between mancozeb exposure and neural tube defects, but
      not between mancozeb exposure and thyroid cancer.

PMID- 15864903
TI  - National job-exposure matrix in analyses of census-based estimates of
      occupational cancer risk.
AB  - OBJECTIVES: The aim of this study was to increase the understanding of the
      alternative exposure metrics and analysis methods in studies applying job
      exposure matrices in analyses of health outcomes, the association between
      crystalline silica and cancer being used as an example. METHODS: Observed and
      expected numbers of cancer cases during 1971-1995 among Finns born in 1906-1945
      were calculated for 393 occupational categories, as defined in the 1970
      population census. According to the Finnish Cancer Registry, there were 43 433
      lung and 21 444 prostate cancer cases. The Finnish job-exposure matrix (FINJEM)
      provided estimates of the proportion of exposed persons and the mean level of
      exposure among the exposed in each occupation. RESULTS: The most comprehensive
      exposure metric included period- and age-specific estimates of exposure and an
      estimate of occupational stability, but also remarkably simpler metrics gave
      significantly elevated estimates of the risk ratio (RR) between 1.36 and 1.50 for
      lung cancer for occupations with the highest estimated cumulative silica exposure
      (> or = 10 mg/m3-years), allowing a lag time of 20 years. It proved important to
      adjust the risk ratios at least for the socioeconomic status and occupational
      exposure to asbestos. The risk ratios for prostate cancer were close to 1.0 in
      every model. CONCLUSIONS: The results showed that the FINJEM-based analysis was
      able to replicate the well-known association between exposure to crystalline
      silica and lung cancer. The FINJEM-based method gives valid results, and it can
      be used to analyze large sets of register-based data on health outcomes.

PMID- 15864904
TI  - Time to pregnancy among Danish laboratory technicians who were a part of the
      National Birth Cohort.
AB  - OBJECTIVES: The Danish National Birth Cohort was used to examine whether
      laboratory work was associated with reduced fecundity. METHODS: Self-reported
      data on laboratory work and waiting time to pregnancy (0-2, 3-5, 6-12 and > 12
      months) were used for 829 female laboratory technicians interviewed in 1997-2003.
      Altogether 6250 female teachers formed the reference group. A discrete-time
      survival analysis with a complementary log-log link was applied to estimate the
      fecundability ratio between the exposed and unexposed women, with adjustment for
      maternal age, gravidity, smoking, prepregnancy body mass index, and paternal job.
      RESULTS: No difference in time to pregnancy was found between the laboratory
      technicians and teachers or between the laboratory technicians with different
      exposures. The adjusted fecundability ratio for the laboratory technicians was
      0.94 [95% confidence interval (95% CI) 0.86-1.02] for all pregnancies and 0.98
      (95% CI 0.86-1.13) for first pregnancies. A healthy worker effect was found for
      the laboratory technicians working with the work processes under study.
      CONCLUSIONS: The results do not suggest that laboratory work in Denmark at
      present impairs female fecundity.

PMID- 15864905
TI  - Radiologically recognized pleural changes in nonpneumoconiotic silica-exposed
      coal miners.
AB  - OBJECTIVES: Whether nonpneumoconiotic silica-exposed coal miners develop
      radiologically recognizable pleural changes was studied. METHODS: In a
      retrospective follow-up study, the oldest and the most recent chest X-rays of 765
      workers with a profusion category lower than 1/0 according to the International
      Labour Office were read. RESULTS: Altogether 720 (94.1%) workers had no
      abnormalities, and 45 (5.9%) showed some pleural alteration in the first X-ray.
      In 43 (6%) of the 720 with no initial abnormalities, some pleural change was
      detected in the last X-ray. There was a statistical difference (P = 0.022)
      according to silica exposure category [low: 5 (2.4%); medium: 8 (6%); high: 30
      (8%)]. The relative risk for any pleural alteration was significantly increased
      in relation to the silica-exposed group [medium: odds ratio (OR) 5.72, 95%
      confidence interval (95% CI) 1.4-23.5, P = 0.016; high: OR 7.62, 95% CI 2.1-27.2,
      P = 0.002] and to rib alterations (OR 3.74, 95% CI 1.4-9.7, P = 0.007). In 19
      (2.6%) workers with no alterations initially, a costophrenic sinus alteration was
      detected later. Again the silica exposure categories [low: 1 (0.5%); medium: 3
      (2.2%); high: 15 (4.2%)] differed significantly (P = 0.033). The relative risk of
      costophrenic sinus obliteration was significantly increased in relation to the
      silica-exposed group [medium: OR 8.59, 95% CI 0.7-113, P = 0.102; high: OR 16.44,
      95% CI 1.5-177, P = 0.021]. The appearance of two costophrenic sinus
      obliterations and the disappearance of four were detected in the last chest X-ray
      of the 45 workers with some pleural alteration initially. CONCLUSIONS:
      Costophrenic sinus obliteration can be found in nonpneumoconiotic silica-exposed
      coal miners and seems to be associated with silica exposure intensity.

PMID- 15864906
TI  - Risk factors for persistent elbow, forearm and hand pain among computer workers.
AB  - OBJECTIVES: This study examined the influence of work-related and personal
      factors on the prognosis of "severe" elbow, forearm, and wrist-hand pain among
      computer users. METHODS: In a 1-year follow-up study of 6943 computer users, 673
      (10%) participants reported "quite a lot" or more trouble due to elbow, forearm,
      or wrist-hand pain during the 12 months preceding the baseline questionnaire.
      Pain status (recovery versus persistence) at follow-up was examined in relation
      to computer work aspects and ergonomic, psychosocial, and personal factors by
      questionnaire. In addition, data on objectively recorded computer usage were
      available for 42% of the participants during the follow-up, measured by means of
      a program (WorkPaceRecorder) installed on their computers. RESULTS: During the
      follow-up, two-thirds of the baseline cases improved to some degree, but only one
      third experienced substantial improvement. The prognosis was not influenced by
      mouse or keyboard work (time, speed, micropauses, and average activity periods)
      or ergonomic workplace conditions. Keyboard times, however, were very low. Pain
      in other regions was a predictor of persistent arm pain. Except for time
      pressure, female gender, and type-A behavior, the prognosis seemed independent of
      psychosocial workplace factors and personal factors. A few cases with severe pain
      were affected at a level which could be compared to clinical pain conditions.
      CONCLUSIONS: Our results do not support the hypothesis that computer work
      activity or ergonomic conditions influence the prognosis of severe arm pain. This
      result is somewhat surprising and should be tested in other studies. Pain in
      other regions implies a poorer prognosis for arm pain.

PMID- 15864907
TI  - Risk factors for visiting a medical department because of upper-extremity
      musculoskeletal disorders.
AB  - OBJECTIVES: This study followed 279 auto assembly workers over 1 year to identify
      which factors influenced whether a worker would visit the plant medical
      department because of an upper-extremity musculoskeletal problem. METHODS:
      Incident cases were defined as involving workers who had not gone to the plant
      medical department in the preceding 6 months and then subsequently visited the
      medical department with a work-related musculoskeletal disorder that was
      potentially due to repetitive work activity (acute fractures or lacerations were
      excluded). RESULTS: There were 45 cases identified during the study period. Based
      on Cox regression analysis, significant predictors for visiting a medical
      department included exceeding the threshold limit value for hand activity and
      peak force, a history of diabetes, a current diagnosis of carpal tunnel syndrome,
      elbow tendonitis, and age under 40 years. CONCLUSIONS: The results of this study
      are consistent with those of other prospective studies that showed that both
      ergonomic and past medical history are risk factors for an upper-extremity
      musculoskeletal disorder and suggests that there is a healthy worker or survivor
      effect among older workers.

PMID- 15864908
TI  - Task-based estimation of mechanical job exposure in occupational groups.
AB  - OBJECTIVES: This study examined the validity of a common belief in epidemiology
      with respect to work-related musculoskeletal disorders, that individual
      mechanical job exposure is better estimated from tasks performed in the job than
      from the mean exposure of the occupational group. METHODS: Whole-day recordings
      of upper trapezius electromyography were obtained from 24 cleaners and 23 office
      workers. Trapezius activity was analyzed in the level (gap time) and frequency
      (jerk time) dimensions. On the same day, the job of each person was divided into
      periods of active work and breaks by means of continuous observations. The
      bootstrap re-sampling technique was used with this database to compare task-based
      job exposure estimates with estimates based on the occupational mean. For a
      particular person, the task-based estimate was obtained by combining the average
      work and break exposures in the occupation with the personal time proportions of
      the two tasks in the job. RESULTS: The task-based estimates were, in general,
      equivalent to, or less correct than, occupation-based estimates for both exposure
      parameters in both occupations and for individual exposures, as well as for group
      means. This was the result in spite of significant and consistent exposure
      differences between work and breaks, in particular among the cleaners.
      CONCLUSIONS: Even if task exposure contrasts are large, task-based estimates of
      job exposures can be less correct than estimates based on the occupational mean.
      Since collecting and processing task information is costly, it is recommended
      that task-based modeling of mechanical exposure be implemented in studies only
      after careful examination of its possible benefits.

PMID- 15864909
TI  - Effect of aging on performance, muscle activation and perceived stress during
      mentally demanding computer tasks.
AB  - OBJECTIVES: This study examined the effects of age on performance, muscle
      activation, and perceived stress during computer tasks with different levels of
      mental demand. METHODS: Fifteen young and thirteen elderly women performed two
      computer tasks [color word test and reference task] with different levels of
      mental demand but similar physical demands. The performance (clicking frequency,
      percentage of correct answers, and response time for correct answers) and
      electromyography from the forearm, shoulder, and neck muscles were recorded.
      Visual analogue scales were used to measure the participants' perception of the
      stress and difficulty related to the tasks. RESULTS: Performance decreased
      significantly in both groups during the color word test in comparison with
      performance on the reference task. However, the performance reduction was more
      pronounced in the elderly group than in the young group. Likewise, a higher level
      of self-reported stress was found for the elderly participants after the color
      word test. During the reference task higher electromyographic levels and reported
      difficulty were recorded for the elderly group than for the young group.
      CONCLUSIONS: The findings suggest that mental demands affect young and elderly
      women differently. Thus the mentally demanding computer task had a more
      pronounced effect on the elderly than on the young. In contrast to the results in
      the reference task, the same level of muscle activity for most muscles and the
      same level of self-reported difficulty was found in the two groups during the
      color word test. The elderly probably compensated for age-related changes by
      reducing their work speed markedly.

PMID- 15864910
TI  - Occupational relevance of subclavian vein thrombosis in association with thoracic
      outlet syndrome.
AB  - OBJECTIVES: Primary subclavian vein thrombosis ("effort thrombosis") is not
      generally recognized as a work-related disorder, and more knowledge is required
      on the particular biomechanical risks. An extensive biomechanical risk analysis
      was performed for a possible work-related case. CASE REPORT: A hard-working 43
      year-old race-course farrier received successful surgical treatment for
      subclavian vein thrombosis. No congenital abnormalities were apparent. At work,
      the farrier spent 75% of his time with his back bent (generally at > 70 degrees)
      with his right shoulder flexed and abducted, a position that thereby increased
      the pressure on the subclavian vein. High average (and peak) stress ratings for
      the neck and shoulder postures are accompanied by high levels of force and
      considerable repetitiveness. CONCLUSIONS: Taken together, these forms of
      biomechanical overload suggest that the leading cause of the subclavian
      thrombosis suffered by this farrier could have been occupational. Case-control
      studies on this neglected topic are needed to investigate possible associations
      between subclavian vein thrombosis and specific occupational activities.

PMID- 15864911
TI  - On the road to the optimal treatment of lupus nephritis: are we there yet?

PMID- 15864912
TI  - Long-term outcome of patients with diffuse proliferative lupus nephritis treated
      with prednisolone and oral cyclophosphamide followed by azathioprine.
AB  - The short-term outcome of patients with diffuse proliferative lupus nephritis
      (DPLN) has improved with advances in immunosuppressive treatment. However, the
      impact of different immunosuppressive regimens on long-term renal function
      remains to be defined. This prospective cohort study examined the long-term renal
      function and disease relapse in adults with biopsy-proven DPLN, significant
      proteinuria, and hypoalbuminemia, who had been treated with sequential
      immunosuppression comprising prednisolone and oral cyclophosphamide as induction
      followed by low-dose prednisolone and azathioprine as maintenance. Sixty-six
      patients with 68 episodes of DPLN were included, with follow-up of 91.7 +/- 36.7
      months. 82.4% achieved complete remission and 39.1% relapsed during follow-up.
      Patients in partial remission were at higher risk of relapse compared with those
      in complete remission (hazard ratio 6.2, P < 0.001). Serum creatinine remained
      stable over time (P = 0.931), while creatinine clearance showed a significant
      increase with time after treatment (P = 0.032). Three (4.4%) patients had
      doubling of baseline creatinine, but none reached end-stage renal failure or
      died. Univariate and mixed model analyses showed that the evolution of long-term
      renal function was significantly influenced by the chronicity score and
      creatinine clearance at baseline, and by the renal function at one year after
      treatment. These data demonstrate the efficacy of sequential immunosuppression in
      preserving renal function in most Chinese subjects with DPLN. The results also
      indicate that irreversible renal scarring (as reflected by baseline chronicity
      score), renal reserve (as reflected by renal function at baseline and one year),
      and an induction regimen that is effective in preserving the nephron mass are
      critical determinants of long-term renal outcome.

PMID- 15864913
TI  - Association of leukocyte CR1 gene transcription with the disease severity and
      renal involvement in systemic lupus erythematosus.
AB  - The reduced level of complement receptor 1 (CR1) on erythrocytes is speculated as
      a key mechanism contributing to immune complex (IC) overload and exaggerated
      complement (C) activation in systemic lupus erythematosus (SLE). Comparatively,
      fewer studies documented lower levels of CR1 on leukocytes and glomerular
      podocytes in this disease. The decline in E-CR1 is largely believed as an
      acquired phenomenon caused due to the proteolytic cleavage of CR1 from
      erythrocyte membrane. The mechanism underlying reduced CR1 expression on
      nucleated cells is under constant investigation. Recently, reduced leukocytes CR1
      gene transcription had been demonstrated in SLE and was suggested as the main
      cause of decline in leukocyte CR1 (L-CR1). The relationship of L-CR1 gene
      transcription with severity and pathophysiology of disease needs to be
      elucidated. We determined the levels of L-CR1 in 30 active SLE patients and
      compared with normal healthy controls (n = 30). Patients were categorized into
      two groups i.e., with nephritis (n = 14) or without nephritis (n = 16). The
      expression of L-CR1 at transcriptional level was correlated with the levels of
      serum CIC, C3 and anti dsDNA antibodies. The levels of L-CR1 transcription were
      significantly reduced in all SLE patients as compared to controls (P < 0.001).
      This decline in L-CR1 however, was more marked in patients with nephritis than
      those without nephritis. In addition, the serum levels of CIC, anti dsDNA
      antibodies were higher and the levels of serum C3 were lower than the normal
      range in the patients. The difference was much more marked in SLE patients with
      nephritis than those without nephritis. The levels of L-CR1 transcription
      correlated negatively with the levels of CIC and anti dsDNA antibodies and
      positively with serum C3 levels. Thus, between SLE patients with and without
      nephritis, we found significant difference in the levels of L-CR1 transcription
      (P < 0.01), CIC (P < 0.05), anti dsDNA antibodies (P < 0.01) and C3 (P < 0.01).
      Our findings suggest that L-CR1 is drastically reduced in patients with severe
      form of SLE, i.e., lupus nephritis. Determination of L-CR1 expression at
      transcriptional level in addition to disease hallmarks like C3, CIC and anti
      dsDNA antibodies may facilitate the assessment of severity of SLE and
      discrimination between patients with or without renal involvement.

PMID- 15864914
TI  - Relationship of quality of life and physical function measures with disease
      activity in children with systemic lupus erythematosus.
AB  - The objective of this study is to assess relationship of systemic lupus
      erythematosus (SLE) activity with quality of life (QOL) and physical function and
      determine which is more closely correlated with SLE activity in children; and
      identify factors critical to children's QOL. In this cross-sectional study,
      children with SLE and parents completed corresponding versions of physical
      function (Childhood Health Assessment Questionnaire CHAQ), and QOL (Pediatric
      Quality of Life Inventory-PedsQL Generic/Rheumatology modules) questionnaires.
      SLE Disease Activity Index (SLEDAI), Systemic Lupus International Collaborating
      Clinics/ACR Damage Index (SDI), severity, self-concept and socioeconomic status
      (SES) were measured. For 24 children, CHAQ scores significantly correlated with
      SLEDAI (rho = 0.4, p = 0.04), SDI (rho = 0.6, p = 0.004), and associated with
      severity (p = 0.03). PedsQL scores did not significantly correlate with above
      parameters. Higher self-concept/SES correlated (p < 0.05) with better physical
      function and QOL. For 19 parents, the only significant correlation was between
      SLEDAI and Worry domain-Rheumatology module (rho = 0.5, p = 0.01). Lack of strong
      correlation of disease activity with QOL and physical function suggests that they
      are different constructs with partial overlap, and should be considered
      collectively while evaluating the impact of SLE on children/families. Self
      concept and SES should be assessed while measuring QOL in children. Larger sample
      is required to confirm results.

PMID- 15864915
TI  - Antiproteinuric effect of ARB in lupus nephritis patients with persistent
      proteinuria despite immunosuppressive therapy.
AB  - Recent immunosuppressive treatments for lupus nephritis have improved renal
      survival rate, however, there still exists lupus nephritis refractory to these
      treatments. Angiotensin receptor blockers (ARBs) are known not only to decrease
      blood pressure but also to have an independent renoprotecting effect by
      interrupting renin-angiotensin system. The aim of this study was to evaluate
      whether ARBs have an additive effect on refractory lupus nephritis. Enrolled in
      this trial were twelve patients with lupus nephritis who were diagnosed by renal
      biopsy and remained proteinuria despite corticosteroids and/or immunosuppressive
      treatments. ARB, losartan or candesartan, was administered for six months.
      Various clinical parameters were compared before and after ARB administration.
      Proteinuria decreased after ARB treatment in 83% of the patients and the median
      amount of proteinuria significantly decreased from 2530 mg/g Cr to 459 mg/g Cr (P
      = 0.03). In addition, serum albumin and cholesterol levels were significantly
      improved. Systolic blood pressure significantly decreased, but none had symptoms
      of hypotension. The antiproteinuric effect of ARB did not correlate with the
      reduction of blood pressure. Interestingly, higher total complement activity
      levels before ARB treatment were associated with a greater reduction of
      proteinuria. The addition of ARB would be a safe and effective treatment for
      lupus nephritis with persistent proteinuria despite corticosteroids and/or
      immunosuppressive treatments.

PMID- 15864916
TI  - The dietary supplement ephedrine induces beta-adrenergic mediated exacerbation of
      systemic lupus erythematosus in NZM391 mice.
AB  - The dietary supplement and adrenergic receptor agonist ephedrine has been a
      controversial topic as its safety has been questioned. Beta-adrenergic receptor
      (beta-AR) activation causes immunomodulation, which may contribute to promotion
      of autoimmune pathology. This report investigated the ability of ephedrine to
      exacerbate processes associated with autoimmune disease in a lupus-prone mouse
      model. To mimic human supplementation, ephedrine was administered to NZM391
      (lupus-prone) and BALB/c (nonlupus prone) mice orally twice a day for three
      months at a dose of 50 and 100 microg/day. Some ephedrine-treated NZM391 mice
      also were preadministered the beta-AR antagonist propranolol to investigate beta
      AR involvement. Mice were bled monthly, and sera were assayed for a variety of
      lupus manifestations and immunological measurements. In NZM391 males and females,
      both doses of ephedrine significantly increased lupus manifestations, including
      IgG production and organ-directed autoantibody titers, and significantly lowered
      the ratio of IgG2a/IgG1 compared to controls. Ephedrine significantly decreased
      female lifespan and significantly increased circulating populations of plasma
      cells (CD38(hi) CD19(lo) cytoplasmic IgG+) and CD40+ B1a cells, while preventing
      an age-related decrease in the B1a cell population expressing a high level of
      CD5. While ephedrine induced gender-specific immunomodulation in BALB/c mice,
      increases in the lupus manifestations of anti-dsDNA titers and serum urea
      nitrogen were not detected. Preadministration of propranolol decreased lupus
      manifestations and serum levels of IgG and IgE in ephedrine-treated mice, but did
      not block the shift towards IgG1 production. These findings indicate that
      ephedrine via beta-AR can exacerbate lupus symptoms in NZM391 mice and that
      blockade of the beta-ARs on B cells, and not T cells, apparently was of greater
      importance as the inhibition of lupus symptoms corresponded to an inhibition of
      immunoglobulin levels, not a change of Th1/Th2 balance.

PMID- 15864917
TI  - MHC class I expression regulates susceptibility to spontaneous autoimmune disease
      in (NZBxNZW)F1 mice.
AB  - (NZBxNZW)F1 mice spontaneously develop with age an autoimmune disease that
      resembles the human disease, systemic lupus erythematosus (SLE). Previous studies
      have demonstrated that susceptibility to experimentally induced SLE depended on
      the expression of MHC class I molecules: mice deficient in beta2-microglobulin
      did not express cell surface class I and were resistant to the induction of
      experimental SLE. Furthermore, the spontaneous SLE-like disease of (NZBxNZW)F1
      mice was ameliorated by treatment with an agent that reduces MHC class I
      expression, methimazole (MMI). In the present study, the role of MHC class I has
      been examined in (NZBxNZW)F1 mice deficient in beta2-microglobulin expression.
      Homozygous (NZBxNZW)F1 beta2m-/- mice do not express class I or develop CD8+ T
      cells. Surprisingly, they show an increased susceptibility to disease. In sharp
      contrast, heterozygous (NZBxNZW)F1 beta2m+/- express class I, albeit at reduced
      levels, develop normal levels of CD8+ T cells and are less susceptible to
      autoimmune disease, relative to their wild-type litter mates. Taken together,
      these findings suggest that class I expression regulates the development of
      disease, both positively and negatively. We speculate that MHC class I expression
      itself confers susceptibility to disease through presentation of self-peptides,
      while also selecting for a CD8+ suppressor T cell population that mitigates
      disease.

PMID- 15864918
TI  - Autoimmune rheumatic diseases in the intensive care unit: experience from a
      tertiary referral hospital and review of the literature.
AB  - Autoimmune rheumatic diseases (AIRD) are not uncommon in the general population
      and up to one third of hospitalized patients with AIRD may need admission to
      intensive care unit (ICU). This paper describes the causes of admission, the
      clinical features and outcome of 24 AIRD patients admitted to a medical ICU from
      a third level hospital. Thirteen patients had systemic lupus erythematosus
      (54.2%), three rheumatoid arthritis (12.5%), three pulmonary renal syndrome
      (12.5%), two dermatopolymyositis (8.3%), two scleroderma (8.3%) and one
      antiphospholipid syndrome (4.2%). The main causes for ICU admission were
      rheumatic disease flare-up (37.5%), infection (37.5%) and complications derived
      from rheumatic disease (29.1%). Mortality during ICU stay was 16.7% (four
      patients). Excluding shock requiring vasopressor support, no statistical
      difference was found between survivors and nonsurvivors; although there was a
      trend to higher test severity scores (APACHE II, ODIN) in nonsurvivors. Our
      results reveal a lower mortality rate in AIRD patients admitted to the ICU than
      reported previously. Severity scores such as APACHE II are predictors of
      mortality in patients with AIRD in the ICU.

PMID- 15864919
TI  - Spontaneous Achilles tendon rupture in a patient with systemic lupus
      erythematosus due to ischemic necrosis after methyl prednisolone pulse therapy.
AB  - Spontaneous tendon rupture in a patient with systemic lupus erythematosus (SLE)
      is a rare but potentially disabling complication. Minor trauma, local
      inflammation and long term corticosteroid therapy are regarded as possible
      causes. However, ischemic necrosis of the tendon resulting from
      hypercoagulability and methyl prednisolone (MTP) pulse therapy has not been
      reported. We present a 20-year old female, newly diagnosed with lupus, who has
      high titer antiphospholipid antibodies, hyperhomocysteinemia and protein S
      deficiency. Her severe clinical symptoms of lupus were improved after MTP pulse
      therapy. Several days later, cold sensation over the right lower leg developed.
      On day 15 after pulse therapy, acute onset of right heel pain occurred when she
      was ascending stairs. Rupture of the right Achilles tendon was demonstrated by
      sonography and MRI. A Doppler sonography revealed narrowing and abrupt cessation
      of blood flow in the right popliteal artery. Heparin treatment was started. The
      angiography performed two days after heparinization revealed narrow caliber and
      decreased flow of the right tibial artery below the right ankle. Surgical repair
      of the tendon was successful and the pathology of the resected tendon revealed
      focal necrosis, degeneration and capillary proliferation. MTP pulse therapy in a
      lupus patient with hypercoaguable state with hyperhomocysteinemia, protein S
      deficiency and high titer antiphospholipid antibodies may cause spontaneous
      tendon rupture.

PMID- 15864920
TI  - Lupus erythematosus proliferative glomerulonephritis in fetus.
AB  - We report the case of a fetus with proliferative glomerulonephritis in the
      context of maternal systemic lupus erythematosus (SLE). The pattern of the renal
      lesions correspond to the class III of revisited WHO classification of
      glomerulonephritis in SLE. Amniotic fluid analysis showed a high level of albumin
      and the presence of anti-Ro and anti-DNA antibodies that were possibly
      responsible for the renal injury.

PMID- 15864921
TI  - Chronic intestinal pseudo-obstruction associated with biliary tract dilatation in
      a patient with systemic lupus erythematosus.
AB  - We present the case of a 57-year old female patient diagnosed with systemic lupus
      erythematosus (SLE) along with glomerulonephritis and chronic intestinal pseudo
      obstruction (CIPO). Dilatation of bile and pancreatic ducts not associated with
      malignant or litiasic obstruction is reported. The combination of bile duct
      associated with CIPO in a patient with lupus has not been previously reported in
      the literature and it probably suggests a smooth muscle dysmotility.

PMID- 15864922
TI  - Hyperacute renal failure as the initial presentation of systemic lupus
      erythematosus.
AB  - SLE nephritis is usually a slow process that may lead to renal failure many years
      after its first presentation. Success of different therapeutic modalities in
      preventing renal failure is therefore evaluated and compared only after many
      years of treatment. Lately, this conservative philosophy has been challenged with
      the acknowledgment of collapsing glomerulopathy (CG), a recent recognized
      clinical-pathological entity, characterized by rapidly progressive renal failure.
      Despite this ominous description we present an unusual case of a patient who
      presented with systemic lupus erythematosus (SLE) and clinical and pathological
      findings of CG, who completely remitted several weeks after commencing
      immunosuppressive therapy with intravenous cyclophosphamide and prednisolone.

PMID- 15864923
TI  - EuroQol is a useful instrument for assessing the health-related quality of life
      of the patients with systemic lupus erythematosus.

PMID- 15864924
TI  - Aortic thrombosis in antiphospholipid syndrome.

PMID- 15864925
TI  - Sperm may be associated with subfertility independent of oocyte fertilization.
AB  - In vitro fertilization-embryo transfer seems to be an effective treatment for
      unexplained infertility. Some IVF centers always perform intracytoplasmic sperm
      injection in these circumstances being concerned that fertilization failure may
      occur by conventional oocyte insemination. However, other IVF centers perform
      intracytoplasmic sperm injection on half of the oocytes and do conventional
      insemination on the other half. However, if the group with conventional oocyte
      insemination had a good fertilization rate, in the future intracytoplasmic sperm
      injection would not be performed. Other IVF centers would inseminate all the
      oocytes with conventional insemination and not consider intracytoplasmic sperm
      injection in the future unless there were poor fertilization rates. The
      aforementioned studies suggest that prior to considering conventional
      insemination that as a minimum the simple inexpensive hypo-osmotic swelling test
      be performed and strong consideration also be given to the sperm stress test and
      SCSA. Similarly, even though IUI is less risky and costly than IVF-ET, there
      still is a moderate expense and risk involved, especially when superovulation is
      used. Thus, consideration for performing these tests should also be given even
      prior to IUI. This is especially important for subnormal HOST scores where
      pretreatment of the sperm with the protein digestive enzyme chymotrypsin when
      preparing the sperm has been demonstrated to markedly improve pregnancy rates.

PMID- 15864926
TI  - Selective estrogen receptor modulator and selective progesterone receptor
      modulator: therapeutic efficacy in the treatment of uterine leiomyoma.
AB  - Recent advances in endocrinology open a door for clinical application of
      selective estrogen receptor modulator (SERM) and selective progesterone receptor
      modulator (SPRM) in the treatment of uterine leiomyoma. With regard to SERM,
      treatment with raloxifene is shown to reduce leiomyoma size in postmenopausal
      women. Although raloxifene causes shrinkage of leiomyomas in combination with
      gonadotropin-releasing hormone agonist in premenopausal women, the effects of
      monotherapy with raloxifene on leiomyoma growth in premenopausal women remain
      controversial. By contrast, tamoxifen may not be suitable for long-term treatment
      of leiomyomas due to an agonistic action on the endometrium. Treatment with
      progesterone antagonist (RU486) or SPRM (J867) has been demonstrated to inhibit
      leiomyoma growth and improve clinical symptoms in premenopausal women. No serious
      adverse effects associated with SERM or SPRM have been reported. In light of
      therapeutic efficacy and few adverse effects, SERM and SPRM may hold promise as
      novel treatment modalities for leiomyoma. Further studies are warranted to
      determine the optimal strategy for the treatment of leiomyoma with SERM and SPRM.

PMID- 15864927
TI  - Miscarriage in the first trimester according to the presence or absence of the
      progesterone-induced blocking factor at three to five weeks from conception in
      progesterone supplemented women.
AB  - PURPOSE: To determine if the failure to detect the immonomodulatory protein
      progesterone induced blocking factor (PIBF) at three to five weeks of seemingly
      normal pregnancies in women supplemented by extra progesterone is associated with
      a higher miscarriage rate. METHODS: Progesterone-induced blocking factor
      expression by lymphocytes was measured by an immunocytochemistry technique. The
      serum beta human chorionic gonadotropin (hCG) and/or ultrasound were also deemed
      appropriate so that by these criteria there was no evidence of a poor pregnancy.
      The minimum progesterone dosage was 200 mg twice daily vaginal suppositories.
      RESULTS: Progesterone-induced blocking factor was detected in 17/39 (43.5%) of
      pregnant patients at this early time. There were three miscarriages by 12 weeks
      in this group (17.6%). The miscarriage rate was 6/21 (28.5%) in those where it
      was not detected. CONCLUSIONS: There was insufficient power to show significance.
      However there seems to be a trend for higher rates of miscarriage when PIBF is
      absent so these preliminary data encourage continuation of the study.

PMID- 15864928
TI  - Non-homogeneous hyperechogenic echo pattern three days after frozen embryo
      transfer is associated with lower pregnancy rates.
AB  - OBJECTIVE: To evaluate the association of mid-luteal phase echo patterns and
      pregnancy rates (PRs) following frozen embryo transfer (ET). METHODS: Sonographic
      evaluation of endometrial echo patterns was performed three days after ET in the
      first frozen ET cycle of women < 40 years of age who used their own oocytes as
      well as all donor oocyte recipients. RESULTS: The distribution of echo patterns
      and clinical PRs were similar in women using their own eggs and women who used
      donor oocytes; therefore all data was combined. The clinical PR was 49.5% with a
      hyperechogenic echo pattern vs 38.8% with a non-hyperechogenic pattern, p = .007.
      CONCLUSION: A larger study of frozen ET and mid-luteal echo pattern now
      demonstrates conclusions similar to the data from fresh ET in hyperstimulated in
      vitro fertilization (IVF)-ET cycles in that failure to attain a hyperechogenic
      echo pattern three days after ET is associated with lower pregnancy rates.

PMID- 15864929
TI  - Frozen embryo transfer outcome according to reason for freezing the embryos.
AB  - PURPOSE: To determine if cryopreservation influences pregnancy outcome following
      transfer. METHODS: Retrospective cohort analyses of frozen embryo transfer (ET)
      cycles divided into five different categories according to reason for freezing.
      RESULTS: Frozen embryos remaining as a result of failing to conceive with the
      previous fresh transfer or those remaining because of cancellation of fresh ET
      related to inadequate endometrial thickness, result in lower pregnancy rates
      (PRs). CONCLUSIONS: The fact that embryos never deselected in a group whose fresh
      ET was canceled because of risk of ovarian hyperstimulation did not have the best
      results suggests that these oocytes may not be of equal quality to those attained
      with a more modest response.

PMID- 15864930
TI  - Lymphocyte immunotherapy can improve pregnancy outcome following embryo transfer
      (ET) in patients failing to conceive after two previous ET.
AB  - PURPOSE: To determine if lymphocyte immunotherapy (LIT) can improve the outcome
      after embryo transfer (ET) in women failing to have a live delivery after at
      least two previous attempts. METHODS: Women failing to deliver a live baby
      despite at least two previous ET cycles at Cooper Center for IVF irrespective of
      previous failed ET cycles in other centers were offered the option of lymphocyte
      immunotherapy prior to their next ET. They were subsequently matched to the very
      next woman having ET but in whom LIT was never offered or was refused. The
      matching was based on age, number of previous failed ET cycles, type of ET (fresh
      or frozen), and serum follicle stimulating hormone (FSH) level. RESULTS: The
      clinical and viable pregnancy rate was 70.3% and 51.3% for the LIT group vs 45.9%
      and 16.2% for the controls (p < .05). CONCLUSIONS: Lymphocyte immunotherapy may
      help improve outcome following ET in women with previous failures. The data
      should encourage a larger multicenter prospective study.

PMID- 15864931
TI  - Transcervical hysteroscopic myomectomy: long-term effects on abnormal uterine
      bleeding.
AB  - OBJECTIVE: To evaluate the effectiveness of hysteroscopic myomectomy in the
      treatment of symptomatic submucous leiomyomas and long-term outcomes. STUDY
      DESIGN: A total of 107 patients with abnormal uterine bleeding (n = 84) and/or
      infertility (n = 23) were submitted to hysteroscopic resection. MAIN OUTCOME
      MEASURES: control of menorrhagia and reproductive outcome. RESULTS: Abnormal
      uterine bleeding was controlled in 68 out of 84 patients with one procedure; 15
      needed a second procedure for incomplete resection. Five patients had menorrhagic
      pathology relapse. Among 23 patients with associated infertility pregnancy was
      achieved in eight cases, seven went to term and one miscarried; one patient
      needed a second procedure. The mean follow-up was 36 months (24-60). Three
      patients were lost at follow-up. CONCLUSIONS: Transcervical hysteroscopic
      resection of submucous myomas is effective for control of abnormal uterine
      bleeding. Further studies are needed to define the value of such procedure in the
      treatment of infertility. Short and long-term results are strictly correlated to
      the possibility of obtaining a complete resection, which is conditioned by degree
      (0, 1, 2) and number of myomas.

PMID- 15864932
TI  - Lysosomal evaluation of endometrioma capsule epithelium and endometrium of
      patients with or without endometriosis.
AB  - OBJECTIVE: To evaluate the number of lysosomes in glandular epithelia of the
      endometrioma capsule and endometrium from patients with or without endometriosis
      using a histochemical method (acidic phosphate determination) under light
      microscopy. METHOD: We studied 31 selected patients with similar clinical
      features, except for the occurrence of menorrhagia enhanced in patients with
      endometriosis. All patients were submitted to video laparoscopic procedures and
      endometrial biopsies through hysteroscopy during the secretory phase. After
      surgery, the patients were divided into two groups for hysteroscopic data: GI-
      without endometriosis (control, n = 16) and GII--with endometriosis (n = 15). In
      GII, the lysosomes of the endometrioma were also counted (GIIa). RESULTS: The GI
      sample was comprised only of endometrial biopsies. We found that the number of
      lysosomes in the topic endometrial tissue of patients with endometriosis was
      significantly larger than the number in endometrioma. Also, there were more
      lysosomes in the endometrium of patients with endometriosis than in endometrioma
      bearing patients. CONCLUSION: Our data suggest that variations in the number of
      lysosomes may underlie the pathogenesis of endometriosis.

PMID- 15864933
TI  - Laparoscopy treatment of adnexal sterility.
AB  - A total of 113 patients who were examined and treated for matrimonial infertility
      underwent surgical laparoscopy at the Sterility and Infertility Department,
      Clinic of Gynecology and Obstetrics, Clinical Center of Nis. Age distribution in
      the group of patients who were subjected to surgical laparoscopy after diagnosis
      was 31.39 +/- 6.1 years, out of whom 74.3% were treated for primary sterility.
      Out of corrective interventions in laparoscopy, the following procedures were
      performed: adnexiolysis, salpingo-ovariolysis, fimbrioplasty, terminal
      salpingoneostomy, cyst puncture and ovarian incision. During any surgical
      laparoscopy, ovarian biopsy was performed for evaluation of ovarian potency and
      verification of probable histopathological findings. The most commonly used
      technique was salpingo-ovariolysis--in 22.88% of cases, followed by fimbrioplasty
      -18.81%. A total of 42 pregnancies were verified: 36 intrauterine (29 completed
      at full term) and 6 extrauterine pregnancies. Average conception rate in our
      patients was 37.17%, while rate of parturition was 25.66%. The rate of pregnancy
      in different corrective laparoscopic procedures ranged from 18.18%-61.54%. The
      rate of intrauterine pregnancy was the highest after bilateral fimbrioplasty
      (47.83%), and the lowest after bilateral neosalpingostomy--9.09%. The rate of
      delivery after adhesiolysis was 30.8%, after salpingo-ovariolysis--28.8%, after
      fimbrioplasty--18.3%, and after neostomy--12.5% of the time.

PMID- 15864934
TI  - Bacterial infections--the cause of preterm delivery.
AB  - Within diagnostic procedures protocols in preterm delivery, the objective of the
      study was to examine bacterial causes of preterm deliveries in relation to term
      deliveries. The study included 106 patients delivered before term (24 to 37 weeks
      of gestation) and 126 patients with term delivery after 37 to 42 weeks of
      gestation. Bacterial analysis included hospital material: cervix smear in
      patients before the delivery and protective and functional fetal elements.

PMID- 15864935
TI  - Factors associated with initiation and duration of breastfeeding in Greece.
AB  - AIM: Our aim was to study factors affecting the initiation, progress and duration
      of breastfeeding in Greece. METHODS: We studied 938 infants born in 2001 in 17
      maternity hospitals in Greece. RESULTS: The percentage of breastfeeding infants
      was 85.5%. The actual progress of breastfeeding was different from the one that
      the mothers intended to follow. Although the majority of women claimed in the
      beginning that they would breastfeed mainly for four to six months (23.2%) and 12
      14 months (23.1%), the majority had discontinued breastfeeding by the fourth
      month (58.5%) and only 7.3% breastfed for more than one year. The initiation time
      of breastfeeding was positively influenced by natural delivery (p = 0) and
      pleasant delivery (p = 0.397). Smoking was negatively associated with the
      duration of breastfeeding (p = 0) and the infants of smokers breastfed mainly for
      one to two months (38.7%). Exclusive breastfeeding in the maternity hospital was
      positively associated with the mother's intention to refuse to use a mixed diet
      after being discharged (p = 0). CONCLUSION: Greater support is needed so that
      women can implement their original intentions concerning the progress of
      breastfeeding.

PMID- 15864936
TI  - Serum leptin and erythropoietin during menstruation.
AB  - OBJECTIVE: The potential influence of leptin and erythropoietin on the
      angiogenesis and bleeding of the endometrium during normal menstrual cycles and
      possible correlations between them. STUDY DESIGN: Serum concentrations of leptin
      and erythopoietin were measured at menstrual days 20, 1 and 3 or 4 in healthy,
      non-obese, normal menstruating women. RESULTS: Mean leptin and erythropoietin
      concentrations showed no significant alteration over time (F = 0.588, p = 0.563
      and F = 0.654, p = 0.528, respectively). There was, however, a strong negative
      linear relationship between the concentration of the two substances on days 1 and
      3 or 4 (p = 0.018 and p = 0.028, respectively). CONCLUSIONS: If the two
      substances affect endometrial angiogenesis, they may do this in a locally limited
      way, so that peripheral concentration changes cannot be observed. Their inverse
      correlation prompts further study with receptor determination.

PMID- 15864938
TI  - Recurrent miscarriage associated with antiphospholipid antibodies: prophylactic
      treatment with low-dose aspirin and fish oil derivates.
AB  - PROBLEM: The aim of this study was to evaluate the effects of two different
      prophylactic protocols, low-dose aspirin and fish oil derivates, in the treatment
      of patients with recurrent pregnancy loss associated with antiphospholipid
      antibodies (APA) syndrome. METHODS: A prospective study included 30 patients who
      were alternately assigned to treatment. Each patient had had at least two
      consecutive spontaneous abortions, positive antiphospholipid antibodies on two
      occasions, and a complete evaluation. RESULTS: Among patients treated with low
      dose aspirin, 12 out of the 15 (80%) pregnancies ended in live births. In the
      fish oil derivate group 11 out of the 15 (73.3%) ended in live births (p > 0.05).
      There were no significant differences between the low-dose aspirin and the fish
      oil derivates groups with respect to gestational age at delivery (39.9 +/- 0.4 vs
      39 +/- 1.5 weeks), fetal birth weight (3290 +/- 200g vs 3560 +/- 100 g), number
      of cesarean sections (25% vs 18%), or complications. CONCLUSION: There were no
      significant differences in terms of pregnancy outcome between women with
      recurrent pregnancy loss associated with APA syndrome treated with low-dose
      aspirin or fish oil derivates.

PMID- 15864937
TI  - The use of tramadol and morphine for pain relief after abdominal hysterectomy.
AB  - OBJECTIVE: The aim of this study was to determine whether the addition of a
      tramadol infusion to morphine patient-controlled analgesia (PCA) results in
      improved analgesic efficacy compared with morphine PCA alone after abdominal
      hysterectomy. METHODS: Sixty patients undergoing abdominal hysterectomy were
      randomized into two groups, each receiving IV morphine PCA after surgery. The
      tramadol group received a loading dose of tramadol (1 mg/kg) at skin closure and
      a postoperative infusion of tramadol at 0.2 mg/kg/h. The control group received
      an equivalent volume of saline at skin closure and a postoperative saline
      infusion. RESULTS: The addition of a tramadol infusion to morphine PCA was
      associated with lower pain scores, a reduction in PCA morphine requirements (27
      +/- 4.6 mg vs 40.5 +/- 5.4 mg over 24 h) and improved patient satisfaction with
      pain relief (p < 0.05). No intergroup differences were found with regard to
      sedation, nausea and antiemetic use (p > 0.05). CONCLUSION: The addition of a
      tramadol infusion to morphine PCA resulted in improved analgesic efficacy and
      reduced morphine requirements compared with morphine PCA alone after abdominal
      hysterectomy.

PMID- 15864939
TI  - Cervix cancer screening among Greek and immigrant women: the experience of a
      Greek District Hospital.
AB  - PURPOSE: To explore whether there are differences in Papanicolaou (Pap) smear
      screening between native and immigrant women that attended our outpatient clinic.
      METHODS: In this retrospective study, from January 2002 until December 2003 we
      examined age, nationality, marital status, economic status (self-reported family
      income per year) and previous Pap test screening frequency; 3,316 women were
      included in the study. RESULTS: The average age was 41.95 years. The majority of
      the women who had had a Pap test (58.4%) were Greeks and 41.6% immigrants.
      Regarding marital status a percentage of 61.2% were married, 13.7% were single
      and 24.9% were divorced. Regarding economic status 71.0% of the women had a low
      income, 25.1% a middle-income and 3.8% a high-income. Of the women 24.99% had
      never had a Pap test in their lives. DISCUSSION/CONCLUSION: The possibility of
      having easy access to a clinic and to routine health care has a critical
      influence on the cancer screening habits of immigrant women. Opportunistic Pap
      smear screening as part of a pregnancy or family-planning checkup in local
      clinics is an acceptable strategy for poor immigrant women.

PMID- 15864940
TI  - Delivery and immigration: the experience of a Greek Hospital.
AB  - INTRODUCTION: In this retrospective study we investigate the differences
      regarding the mode of delivery between Greek and immigrant women. MATERIAL AND
      METHODS: We collected data from the Birth Registry of the hospital delivery room
      for the period from March 1, 2000 to February 29, 2004. We assigned the women
      into two groups according to their nationality: Greeks and immigrants. We studied
      the following parameters: age, nationality, parity of women, mode of delivery
      instrumental delivery (ID), vaginal birth (VD), cesarean section (CS), the
      indications of CS, and gender and weight of the newborn; 3,071 women met the
      inclusion criteria. RESULTS: The average immigrant's age was 2.9 years lower than
      in the Greek group; 35.2% of the women were Greeks and 64.7% were immigrants. A
      significant difference was found in the percentage of multipara and the
      indications for CS--especially prolonged labor (significantly higher in the
      immigrants), and preeclampsia (significantly higher in the Greeks). There were no
      significant differences between the two groups referring to the rate of CS, ID or
      VD, the gender of the newborn, and the birth weight. DISCUSSION/CONCLUSION: We
      did not find any significant differences between the two groups regarding the
      rate of caesarean delivery. In exploring health-related differences between
      population groups, it is important to determine how race/ethnicity contributes to
      these differences. A statistically significant association between race or
      ethnicity and an undesirable health outcome does not by itself establish
      causality. Health outcomes usually have multiple causes that can be either direct
      or indirect and are often interrelated and interactive. Race/ethnicity and social
      class influence health through complex pathways.

PMID- 15864941
TI  - Effect of depleted uranium weapons used in the Balkan war on the incidence of
      cervical intraepithelial neoplasia (CIN) and invasive cancer of the cervix in
      Greece.
AB  - OBJECTIVE: To compare the incidence rates of CIN and invasive cancer of the
      cervix in two district areas near the borders with the former Yugoslavia and an
      urban area away from these borders three years before and three years after the
      bombings in this country. MATERIAL: Two peripheral hospitals (in Kilkis and
      Serres) which are near the border with the former Yugoslavia and one University
      hospital (Hippocratio hospital of Thessaloniki) in a rural area away from the
      borders, where routine Papanicolaou smear tests for screening of CIN and invasive
      cancer of the cervix are performed in the general female population. METHODS:
      Hospital records were searched for abnormal smear test results. Incidence rates
      of CIN and invasive cancer of the cervix three years before (1997-1999) and three
      years after (2000-2002) the bombings were calculated and compared in the three
      different settings. The relation between the mean age of the first occurrence of
      an abnormal smear test was also examined. The results were examined using the chi
      square test. RESULTS: The incidence of CIN in the three-year period 1997-1999 was
      0.68% and 0.9% for the two district hospitals of Kilkis and Serres, respectively.
      These figures rose to 1.11% and 1.13% in the three-year period 2000-2002 for the
      two district hospitals. The incidence of CIN in the three-year period 1997-1999
      was 1.06% for the Hippokrateion University Hospital of Thessaloniki and 0.88% for
      the three-year period 2000-2002. There has been a small but not statistically
      significant increase in the incidence rates of CIN in the two district areas near
      the borders with the former Yugoslavia over the last few years (p = 0.355 for
      Kilkis and p = 0.472 for Serres), compared with the small but statistically
      significant decrease in the incidence of CIN in the urban area of Thessaloniki (p
      = 0.0275). The rates of invasive cancer of the cervix diagnosed from the routine
      smear tests were too small to make any conclusions. CONCLUSION: The increase in
      the incidence of precancerous lesions of the cervix in areas near the borders
      with the former Yugoslavia during the last three years may be influenced by
      environmental factors such as exposure to depleted uranium due to the bombings of
      1999. To comfirm this bigger epidemiological studies are needed.

PMID- 15864942
TI  - Artificial fetal lung maturation--prevention of antenatal complications in
      premature deliveries.
AB  - Keeping in mind the frequency of preterm deliveries as well as the morbidity and
      mortality of the newborn population, many ways of bringing about faster
      maturation of the fetus have been. Today, we can say that after the 24th week of
      gestation, when the pneumocites time 2 are anatomically formatted, medical
      treatment of the fetus for maturation not only of the lungs but all the
      vulnerable organs is available. By stimulating the pneumocites to make surfactant
      and sphingomyeline and phosphatidilinositol and phosphatidilglycerol, we can
      reduce respiratory distress syndrome. Moreover, the frequency of intracranial
      haemorage is lowered. We have performed many studies with all of their positive
      and negative effects, including: use of corticosteroids, thyroxine,
      aminophilline, surfactant, inositole and beta adrenergic agonist.

PMID- 15864943
TI  - Perinatal outcome in multiple pregnancies--spontaneous gestation versus.
AB  - The purpose of this investigation was to determine if twin pregnancies induced by
      in vitro fertilization (IVF) are under greater risk of negative perinatal outcome
      than "spontaneous" twin pregnancies. The study included 240 patients with
      gemellar pregnancies. Each patient with a gemellar IVF pregnancy (120) was
      assigned to a pregnant woman with appropriate age, education and parity from the
      "spontaneous" group as a control. Pregnancies were followed clinically, with
      laboratory analyses and ultrasonography.

PMID- 15864944
TI  - Managing anemia in gynecologic surgery with postoperative administration of
      recombinant human epoetins.
AB  - OBJECTIVE: To investigate whether postoperative administration of erythropoietin
      can safely augment in the rapid restoration of hemoglobin (Hgb) values following
      major gynecologic surgery. METHODS: Thirty-three women were enrolled. They had
      all undergone gynecologic surgery due to malignant or non-malignant reasons.
      Because of chronic blood loss, many of these patients were iron depleted.
      Examinations of hematology, serum chemistry and urinalysis values were obtained.
      Subcutaneous administration of r-HuEPO, in a dosage of 40,000 IU was initiated on
      the first postoperative day. One additional injection of 40,000 IU was given on
      the fourth day after surgery. Contemporarily the patients received orally a
      polysaccharide-iron complex. RESULTS: During the early postoperative period three
      patients that were transfused due to severe anemia and one more that was lost in
      follow-up were excluded from the study analysis. The remaining 29 patients showed
      a considerable rise in Hgb counts that reached a median value of 1.9 g/dl within
      a 20-day period. CONCLUSION: The postoperative administration of r-HuEPO in
      gynecologic surgery in patients where autologous blood transfusions can be
      avoided is challenging, since it can guarantee an uneventful postoperative period
      with rapid resuscitation without posing the patient to the well-established risks
      of transfusions.

PMID- 15864945
TI  - Epidemiology of congenital anomalies in different ethnicities.
AB  - PURPOSE OF INVESTIGATION: To study the prevalence and the epidemiologic
      characteristics of major congenital anomalies (MCAs) in two different populations
      in Thrace-Greece. METHODS: The ethnic origin of all mothers who delivered in our
      department and the types of MCAs were determined. We compared the frequencies of
      MCAs between Christians and Muslims. The chi-square test, t-test, binary and
      multinomial logistic regression analysis were performed. RESULTS: The prevalence
      of MCAs was significantly higher in Muslims as compared to Christians (51/4,028
      (12.78%) vs 49/5,994 (8.17%), p = 0.035). However, the frequencies of each type
      of MCA in the total number of deliveries between the two groups did not differ
      significantly. The central nervous system malformations were most frequently
      associated with perinatal mortality. CONCLUSION: This is the first study in
      Greece showing that there is probably a higher prevalence of MCAs in Muslims as
      compared to Christians, although it can not be elucidated whether this increased
      risk is related to specific differences between them.

PMID- 15864947
TI  - Isotretinoin (Ro-Accutane) teratogenesis. A case report.
AB  - A case of teratogenesis in a 16-year-old pregnant patient is described. She had
      been using 60 mg Ro-Accutane daily till the 16th week of gestation. Sonography
      showed no cephalic skull up to the frontal bone of the fetus. A central
      lagostroma was also detected.

PMID- 15864946
TI  - Live delivery following transfer of a single frozen-thawed embryo derived from a
      42-year-old woman with marked decreased oocyte reserve.
AB  - PURPOSE: To determine if live birth is possible in a woman of older reproductive
      age and who has markedly decreased oocyte reserve following frozen embryo
      transfer of an oocyte fertilized by intracytoplasmic sperm injection of
      testicular sperm. METHODS: Ethinyl estradiol followed by ovarian stimulation with
      gonadotropins was used and a mature follicle was attained. Following oocyte
      retrieval 34 hours later, intracytoplasmic sperm injection of testicular sperm
      was performed. The embryo was cryopreserved. RESULTS: A live delivery of a full
      term baby ensued. Following subsequent frozen embryo transfer, the baby was
      diagnosed with Down's syndrome and subsequently died. CONCLUSION: This is the
      first report of a live delivery following frozen embryo transfer in a woman of
      advanced reproductive age with marked decreased oocyte reserve.

PMID- 15864948
TI  - Ectopic missed abortion after laparoscopic sterilization with the harmonic
      scalpel.
AB  - A case of a patient who presented with ectopic pregnancy and subsequent missed
      abortion one year after laparoscopic sterilization with the harmonic scalpel is
      reported. According to our knowledge of the relevant literature, this is the
      first time that a case of ectopic pregnancy after sterilization with a harmonic
      scalpel has been reported.

PMID- 15864949
TI  - Technology needs to be linked to environmental education programmes for more
      efficacious waste management.

PMID- 15864950
TI  - Biodegradability of degradable plastic waste.
AB  - Plastic waste constitutes the third largest waste volume in Malaysian municipal
      solid waste (MSW), next to putrescible waste and paper. The plastic component in
      MSW from Kuala Lumpur averages 24% (by weight), whereas the national mean is
      about 15%. The 144 waste dumps in the country receive about 95% of the MSW,
      including plastic waste. The useful life of the landfills is fast diminishing as
      the plastic waste stays un-degraded for more than 50 years. In this study the
      compostability of polyethylene and pro-oxidant additive-based environmentally
      degradable plastics (EDP) was investigated. Linear low-density polyethylene
      (LLDPE) samples exposed hydrolytically or oxidatively at 60 degrees C showed that
      the abiotic degradation path was oxidative rather than hydrolytic. There was a
      weight loss of 8% and the plastic has been oxidized as shown by the additional
      carbonyl group exhibited in the Fourier transform infra red (FTIR) Spectrum.
      Oxidation rate seemed to be influenced by the amount of pro-oxidant additive, the
      chemical structure and morphology of the plastic samples, and the surface area.
      Composting studies during a 45-day experiment showed that the percentage
      elongation (reduction) was 20% for McD samples [high-density polyethylene, (HDPE)
      with 3% additive] and LL samples (LLDPE with 7% additive) and 18% reduction for
      totally degradable plastic (TDP) samples (HDPE with 3% additive). Lastly,
      microbial experiments using Pseudomonas aeroginosa on carbon-free media with
      degradable plastic samples as the sole carbon source, showed confirmatory
      results. A positive bacterial growth and a weight loss of 2.2% for degraded
      polyethylene samples were evident to show that the degradable plastic is
      biodegradable.

PMID- 15864951
TI  - Composting dynamics and optimum mixture ratio of chicken manure and vineyard
      wastes.
AB  - Vineyard waste and chicken manure mixtures are useful materials for composting
      but when these wastes are composted alone, many environmental problems occur
      because of their chemical characteristics. Whereas chicken manure is a very rich
      source of nitrogen, vineyard waste has a very high carbon content. In the present
      study experiments to determine an optimum mixture ratio of chicken manure and
      vineyard waste for composting were performed. The results showed that the optimum
      mixture ratio for composting these materials was 50% chicken manure and 50%
      vineyard waste on a dry basis.

PMID- 15864952
TI  - Chemical and microbiological stability of waste sludge from paper industry
      intended for brick production.
AB  - Due to its chemical composition, waste sludge generated in the paper industry may
      be used as a raw material for brick production. Brick manufacture is limited to
      the warmer months of the year whereas sludge is produced continuously by
      different effluent treatment devices. Therefore, it has to be stored until
      further processing. For this reason, it is essential that it is not subject to
      significant chemical and microbiological decomposition during storage. In the
      experiment, sludge from a tissue paper mill was tested for its stability. It was
      stored for several weeks during winter and summer periods in a pile, 2 m in
      height, in an open but covered store. Different leachable organic and inorganic
      compounds indicating possible ongoing deterioration processes, as well as pH
      value, redox potential, temperature, humidity and dry matter content were
      evaluated weekly in water extracts of homogenized sludge samples. According to
      the test results, the material may be considered to be chemically and
      microbiologically stable as there was practically no emission of odorous and
      toxic compounds such as H2S, NH3 and butyric acid despite prolonged storage times
      and elevated environmental temperatures. All the microbial species identified in
      the sludge during storage belong to the typical microflora of the environment.

PMID- 15864953
TI  - Experimental landfill caps for semi-arid and arid climates.
AB  - The United States EPA Subtitle D municipal solid waste landfill requirements
      specify that the permeability of a cap to a landfill be no greater than the
      permeability of the underliner. In recent years the concept of the
      evapotranspirative (ET) cap has been developed in which the cap is designed to
      store all rain infiltration and re-evapotranspire it during dry weather. Concern
      at the long period required for landfilled municipal solid waste to decompose and
      stabilize in arid and semi-arid climates has led to an extension of the concept
      of the ET cap. With the infiltrate-stabilize-evapotranspire (ISE) cap, rain
      infiltration during wet weather is permitted to enter the underlying waste, thus
      accelerating the decomposition and stabilization process. Excess infiltration is
      then removed from both waste and cap by evaporation during dry weather. The paper
      describes the construction and operation of two sets of experimental ISE caps,
      one in a winter rainfall semi-arid climate, and the other in a summer rainfall
      semi-arid climate. Observation of the rainfall, soil evaporation and amount of
      water stored in the caps has allowed water balances to be constructed for caps of
      various thicknesses. These observations show that the ISE concept is viable. In
      the limit, when there is insufficient rainfall to infiltrate the waste, an ISE
      cap operates as an ET cap.

PMID- 15864954
TI  - Heavy metal content of combustible municipal solid waste in Denmark.
AB  - Data on the heavy metal composition of outlets from Danish incinerators was used
      to estimate the concentration of Zn, Cu, Pb, Cr, Ni, Cd, As and Hg in combustible
      waste (wet as received) at 14 Danish incinerators, representing about 80% of the
      waste incinerated in Denmark. Zn (1020 mg kg(-1)), Cu (620 mg kg(-1)) and Pb (370
      mg kg(-1)) showed the highest concentration, whereas Hg (0.6 mg kg(-1)) showed
      the lowest concentration. The variation among the incinerators was in most cases
      within a factor of two to three, except for Cr that in two cases showed
      unexplained high concentrations. The fact that the data represent many
      incinerators and, in several cases, observations from a period of 4 to 5 years
      provides a good statistical basis for evaluating the content of heavy metals in
      combustible Danish waste. Such data may be used for identifying incinerators
      receiving waste with high concentrations of heavy metals suggesting the
      introduction of source control, or, if repeated in time, the data must also be
      used for monitoring the impacts of national regulation controlling heavy metals.
      It is recommended that future investigations consider the use of sample digestion
      methods that ensure complete digestion in order to use the data for determining
      the total heavy metal content of waste.

PMID- 15864955
TI  - Nitrous oxide (N2O) emissions from waste and biomass to energy plants.
AB  - Following the Kyoto protocol with respect to reducing emissions of greenhouse
      gases emissions, and EU energy policy and sustainability in waste management,
      there has been an increased interest in the reduction of emissions from waste
      disposal operations. From the point of view of nitrous oxide (N2O) emissions,
      waste incineration and waste co-combustion are very acceptable methods for waste
      disposal. In order to achieve very low N2O emissions from waste incineration,
      particularly for waste with higher nitrogen content (e.g. sewage sludge), two
      factors are important: temperature of incineration over 900 degrees C and
      avoiding the selective non-catalytic reduction (SNCR) de-NO(X) method based on
      urea or ammonia treatments. The more modern selective catalytic reduction (SCR)
      systems for de-NO(X) give rise to negligible sources of N2O.

PMID- 15864956
TI  - Nickel recovery from spent nickel catalyst.
AB  - A process for nickel recovery from a spent catalyst of definite composition has
      been developed using the hydro-metallurgical route. The processing steps includes
      direct sulphuric acid leaching followed by separation of iron as well as silica
      and other impurities. For a 152 microm particle size catalyst, extraction of
      about 98% nickel was achieved at 363 K in 2 h using a sulphuric acid
      concentration (v/v) of 8% and a pulp density of 10%. The dissolution of nickel
      followed diffusion-controlled leaching kinetics. Increase in temperature and
      sulphuric acid concentration resulted in increase in the nickel recovery. The
      activation energy for nickel dissolution was calculated to be 62.8 kJ mol(-1).
      Finally, nickel was recovered as value-added products such as sulphide and
      oxalate with overall recovery of 90 and 88% of nickel, respectively.

PMID- 15864957
TI  - Dynamic modelling of packaging material flow systems.
AB  - A dynamic model has been developed for reused and recycled packaging material
      flows. It allows a rigorous description of the flows and stocks during the
      transition to new targets imposed by legislation, product demand variations or
      even by variations in consumer discard behaviour. Given the annual reuse and
      recycle frequency and packaging lifetime, the model determines all packaging
      flows (e.g., consumption and reuse) and variables through which environmental
      policy is formulated, such as recycling, waste and reuse rates and it identifies
      the minimum number of variables to be surveyed for complete packaging flow
      monitoring. Simulation of the transition to the new flow conditions is given for
      flows of packaging materials in Greece, based on 1995--1998 field inventory and
      statistical data.

PMID- 15864958
TI  - Nasreya: a treatment and disposal facility for industrial hazardous waste in
      Alexandria, Egypt: phase I.
AB  - A facility for the treatment and disposal of industrial hazardous waste has been
      established in Alexandria, Egypt. Phase I of the facility encompassing a secure
      landfill and solar evaporation ponds is ready to receive waste, and Phase II
      encompassing physico-chemical treatment, solidification, and interim storage is
      underway. The facility, the Nasreya Centre, is the first of its kind in Egypt,
      and represents the nucleus for the integration, improvement and further expansion
      of different hazardous waste management practices and services in Alexandria. It
      has been developed within the overall legal framework of the Egyptian Law for the
      Environment, and is expected to improve prospects for enforcement of the
      regulatory requirements specified in this law. It has been developed with the
      overall aim of promoting the establishment of an integrated industrial hazardous
      waste management system in Alexandria, serving as a demonstration to be
      replicated elsewhere in Egypt. For Phase I, the Centre only accepts inorganic
      industrial wastes. In this respect, a waste acceptance policy has been developed,
      which is expected to be reviewed during Phase II, with an expansion of the waste
      types accepted.

PMID- 15864959
TI  - [Surgical care rendered to the wounded in the antiterrorist operations on the
      Northern Caucasus: premedical and initial medical care in the combat zone (Report
      II)].
AB  - The analysis of organization and contents of the first aid, premedical and
      initial medical care rendered to the wounded in the armed conflicts on the
      Northern Caucasus (1994-1996, 1999-2002) was conducted. It was established that
      the first aid was rendered to the most casualties who needed it (65% in the first
      conflict and 79% in the second conflict). The mean terms of rendering the first
      aid in the second conflict as compared with the conflict of 1994-1996 were
      decreased from 29 +/- 2 min to 18 +/- min. The role of premedical care was
      minimal in both conflicts: it was rendered to 3% casualties only. The premedical
      care was rendered in those cases when the first aid appeared to be ineffective,
      had obvious defects or in the delay of further evacuation of the wounded. The
      initial medical care became the central type or pre-hospital care in the combat
      zone. It was rendered to 56% casualties in the first conflict and to 59% in the
      second conflict. The mean terms of initial medical care rendered in the second
      armed conflict were 1.5 +/- 0.2 h. They have considerably decreased as compare
      with the first conflict (2.5 +/- 0.4 h). The introduction of the physicians with
      initial surgery and intensive care training in the staffs of regimental medical
      companies was resulted in significant improvement of initial medical care
      quality. It provided the adequate preparedness of the wounded for aeromedical
      evacuation to multipurpose military hospitals of the first level.

PMID- 15864960
TI  - [Medicolegal analysis of ARD mass cases occurred in servicemen].
AB  - The article presents the analysis of causes and outcomes of ARD and pneumonia
      incidence among the servicemen in one of the military units during the period
      2002-2003. 95 forensic medical examinations were analyzed. The terms of disease
      occurrence, complications, unfavorable outcomes are presented. The defects in
      medical care rendering are shown. The recommendations on prophylaxis of such
      cases are shown.

PMID- 15864961
TI  - [Orthopedic stage of the complex treatment of the casualties with maxilla
      defect].

PMID- 15864962
TI  - [The first experience and technical problems of xenon use in anesthesiology].

PMID- 15864963
TI  - [Changes in erythrocyte count during blood laser radiation].

PMID- 15864964
TI  - [Epidemiology and prophylaxis of influenza and other acute respiratory infections
      occurred in the military collectives].
AB  - The long complex study of epidemiology of influenza and other acute respiratory
      infections (ARI) was conducted by the specialists from General and Military
      Epidemiology Department of the Military Medical Academy collaboration with
      specialists of Civilian and Military Health Service. The study has revealed the
      causes of ARI high incidence in the Army and Fleet, allowed to establish the risk
      groups, the reservoirs of circulating infectious agents, the criteria of
      premorbid diagnosis of servicemen' susceptibility to often diseases and formation
      of chronic virus carriage. Besides the different vaccines against influenza,
      adenovirus and mycoplasma, immunostimulators, other measures of urgent
      prophylaxis including their various combinations were studied. Many of them as an
      inactivated influenza vaccine are used according the epidemiological situation.
      The experience gained and cooperative practice of military and civilian
      epidemiologists are realized in the interests of sanitary-and epidemiologic
      inspection and prophylaxis of influenza and other ARI, aerosolic anthroponosis in
      the Armed Forces as well as among the civilian population. It can be used in
      creation of global system for infection control.

PMID- 15864965
TI  - [The improvement of informative-and-analytical works in the field of military-and
      professional traumatism prophylaxis].

PMID- 15864966
TI  - [Partisans marched out (from the memorials of a military doctor)].

PMID- 15864967
TI  - [Treatment-and Diagnostic Center of RF AF General Headquarters is 60 years].

PMID- 15864968
TI  - [The Grand Duchess Ellen Pavlovna: her activities during the period of Crimean
      War].

PMID- 15864970
TI  - A preliminary study of EAT and BITE scores for one school year in Bermuda:
      increased early anorexic measures related to socio-economic factors.
AB  - BACKGROUND: Bermuda is a unique heterogeneous ethnic population in which it is
      possible to study the interaction of ethnicity, culture, gender and economic
      factors that influence abnormal eating attitudes. METHOD: A cross-sectional
      survey of 836 adolescents, one total school year in Bermuda. The BITE and EAT
      self-report questionnaires were administered in a classroom setting. The analysis
      was for caseness and for total scores. Caseness represents possible developing
      anorexic or bulimic eating disorder pathology for this non-adult population.
      RESULTS: 7.3% fulfilled EAT caseness, 0.24% fulfilled BITE caseness. There was no
      gender or ethnic difference for caseness. Multivariate analysis for EAT caseness
      found Odds Ratios of 2.89 (95% CI 1.37, 6.11) for Manual maternal job status.
      CONCLUSION: Despite the limitation of a questionnaire analysis, lower
      socioeconomic status increases the risk of possible eating disorder pathology in
      this adolescent population. Developing anorexic eating attitudes were more
      prevalent compared to bulimic attitudes for schoolchildren in this unique
      cultural setting.

PMID- 15864971
TI  - Responsibility attitude in a sample of Iranian obsessive-compulsive patients.
AB  - BACKGROUND: The study of distorted beliefs about responsibility attitude and
      interpretation has become the central theme in Salkovskis' (1985) and Rachman and
      Hodgson's (1980) models of Obsessive-Compulsive Disorder (OCD). AIMS: The aim of
      this research is to assess the responsibility attitude in Iranian OCD patients.
      METHODS: Twenty OCD patients were selected through available sampling from the
      case referred to psychology clinics. Two other patient groups comprised of 20 non
      OCD anxiety disorder patients and 20 non-clinical participants were also chosen
      as comparison groups. All participants completed the Responsibility Attitude
      Scale (RAS) and Responsibility Interpretation Questionnaire (RIQ). RESULTS:
      Analyses revealed statistically significant differences between OCD group and
      comparison groups on both RAS and RIQ. In addition, both RAS and RIQ scores were
      associated with the severity of OCD assessed by the Yale-Brown scale.
      CONCLUSIONS: These findings suggest that responsibility attitude and
      interpretations are the prominent features of OCD in Iranian patients and are
      associated with the severity of illness.

PMID- 15864972
TI  - Social services and health services day care in mental health: the social
      networks and care needs of their users.
AB  - BACKGROUND: In view of the increasing integration of health and social care,
      there is an urgent need to know how health service day hospitals and social
      service day centres are being used, and by whom. AIMS: We aimed to compare users
      of day hospitals and centres in terms of their social networks, needs for care
      and demographics. METHODS: A cross-sectional, comparative study of service users
      at two day hospitals and four day centres compared their social networks, needs
      and characteristics. RESULTS: Day centre clients had much larger social networks,
      including a three-fold difference in total contacts and two-fold difference in
      confidants, but had more needs for care, particularly relating to psychological
      distress. They were also older on average than day hospital patients and were a
      more long-term group. CONCLUSION: It is vital to understand differences between
      health service day hospitals and social service day centres given the increasing
      integration of health and social care. The present study shows that the two user
      groups are significantly different. It is unlikely that the needs of most day
      care users could be met by either service interchangeably.

PMID- 15864973
TI  - The use of carers' and users' expectations of services (CUES) in an
      epidemiological survey of need.
AB  - BACKGROUND AND METHOD: This study surveyed need in a group of psychiatric
      patients in Gloucester, using a new instrument, the CUES. Keyworkers gave out
      questionnaires to all patients with psychosis in contact with specialist
      services. A total of 148 forms were anonymously completed, with a response rate
      of 37% of the mental health services caseload. RESULTS: 53.5 to 83.2% of patients
      were satisfied and 61.5 to 89.6% expressed their experiences 'as good as' a
      normative statement across the 16 domains. There was mostly 'moderate' agreement
      between satisfaction and normative questions by Kappa correlations, although
      responses to normative questions tended to be about 10% higher. Extensive free
      text responses were subject to content analysis, demonstrating needs across a
      wide range of health, social and leisure areas, many of which were not directly
      linked to the adequacy or otherwise of psychiatric treatment. CONCLUSIONS: The
      results imply that the CUES may be of value at an individual level to aid in care
      planning, and also have some value in aggregated form to benchmark user
      experiences of services.

PMID- 15864974
TI  - Goals of new long-stay patients in supported housing: a UK study.
AB  - AIM: This study assessed the goals 'new' long-stay clients aim to achieve by
      being in supported housing (SH), compared the goals stated by clients and staff,
      and tested whether subgroups of clients can be identified on the basis of their
      goals, quality of life and psychopathology. METHOD: Interviews were conducted
      with 41 clients and 39 staff of supported houses in London and Essex, UK.
      Descriptive, content and cluster analyses were used to analyse the results.
      RESULTS: Clients' most frequently reported goal was moving to independent
      housing, followed by staying healthy, and increasing living skills. A comparison
      of goals reported by clients and staff showed poor or no agreement between them.
      Cluster analyses identified two clusters of clients. Cluster A (n = 23) contained
      those with no stated goals (or with the aim of staying healthy), lower quality of
      life, and more psychopathology; cluster B (n = 18) included those with an aim to
      move to independent housing, better quality of life, and less psychopathology.
      CONCLUSION: In the UK, more staff training may be needed to identify and achieve
      the goals of the 'new' long-stay clients. For a subgroup of these clients, SH may
      still be a long-term care setting; while for another subgroup, new forms of
      rehabilitation in SH and better opportunities to leave SH may have to be
      developed. More conceptual and practical efforts are needed to manage the
      transformation of many settings from homes for life to transitional places where
      residents receive specific interventions.

PMID- 15864975
TI  - Determinants of duration of untreated psychosis and the pathway to care in
      Singapore.
AB  - INTRODUCTION: Delays in providing effective treatment for a patient with
      psychosis has significant negative effects on the outcome. This includes more
      hospitalizations, longer periods of inpatient care, slower and less complete
      recovery, and more frequent relapses. In this study, we established the Duration
      of Psychosis (DUP) in a sample of patients with first-episode psychosis and
      examined the pathways to care. METHODS: The sample comprised patients presenting
      with first-episode psychosis to the psychiatric services of the Institute of
      Mental Health, Singapore, from January to December 2000. The association between
      the DUP and demographic, clinical and social variables was examined. RESULTS: The
      DUP ranged from 0.1 to 336 months. The mean DUP was 32.6 (SD = 59.8) months, with
      a median of 12 months. Twenty four percent of the patients had sought
      consultation with a traditional healer prior to consulting a psychiatrist. The
      DUP of this group of patients was not significantly different from those who
      sought help elsewhere. CONCLUSIONS: The DUP of our patients was longer than that
      reported in studies done in the West. The attitudes and beliefs of family in the
      Asian society are likely to be crucial in the pathways to care.

PMID- 15864976
TI  - Microcounseling skills training for informal helpers in Uganda.
AB  - BACKGROUND: Years of political instability, civil unrest, and disease have left
      scores of Ugandans in need of mental health services. However, there are few
      formal mental health services available in the country. Professional helpers such
      as clergy, teachers, and healthcare workers who have strong ties to their
      communities are frequently placed in formal counseling roles. AIMS: To develop,
      implement, and evaluate a training model for developing micro-counseling skills
      designed specifically for informal helpers in Uganda. METHODS: Forty-four
      professional helpers were provided with a one-week, 40-hour training program in
      microcounseling skills. RESULTS: Following the training program, trainees
      demonstrated proficiency in basic counseling skills and attained an increased
      knowledge of those skills. CONCLUSIONS: This training was readily assimilated and
      supported the ecological validity of the microcounseling model.

PMID- 15864977
TI  - On the relationship between cultural values and preferences and affective health
      in Nepal.
AB  - BACKGROUND: The westernization of developing countries has improved physical
      health and life expectancy. Modernization, however, is believed to have injurious
      effects on mental health. Some research suggests that the effects of
      modernization vary, hurting some but benefiting others. Economic disparity is
      usually presumed to cause the mental health problems. The purpose of this study
      was to determine if aspects of westernization other than economic status
      predicted depression scores in a sample of adults occupying similar economic
      stations in Nepal. METHODS: Survey data were collected from 276 teachers in
      Nepal. The questionnaire was administered in Nepali. Statistical tests sought to
      determine the relationship between scores on a measure of depression and having a
      western cultural orientation. RESULTS: Bivariate and multi-variate analyses
      indicate that a higher western orientation was associated with lower depression
      scores. Non-traditional attitudes towards the Nepalese caste system and gender
      political equality predicted lower depression scores. Attitudes regarding gender
      economic equality and a preference for western music and film and English
      language were not associated with depression scores. CONCLUSION: Findings suggest
      that the relationship between modernization and psychological well-being are
      contextual.

PMID- 15864978
TI  - Treatment of schizophrenia: implications derived from an intercultural hospital
      comparison between Germany and Japan.
AB  - OBJECTIVES: The study was aimed at evaluating facets of psychiatric inpatient
      care of patients with schizophrenia in a German and a Japanese hospital. METHODS:
      Based upon a sample of 865 inpatients of the Psychiatric State Hospital
      Regensburg (BKR) and 50 inpatients of the Tokyo Women's Medical University (TWMU)
      admitted in 1997, data of a psychiatric basic documentation system (BADO) were
      analysed with regard to essential process and outcome indicators. RESULTS:
      Despite dissimilarities between both patient groups with respect to schizophrenic
      subtype, duration of illness as well as severity of illness and psychosocial
      functioning, the differences regarding therapeutic treatment and outcome were
      marked. In 1997, the rate of atypical neuroleptics was 18% at the BKR and 12% at
      the TWMU. Inpatients of the TWMU were given benzodiazepines and anticholinergic
      drugs significantly more frequently. Male patients of the TWMU showed more severe
      side-effects. Psychotherapy and sociotherapy were less frequently applied at the
      TWMU. Although the patient groups did not differ with regard to suicidal
      behaviour and overt aggressions during hospitalisation, we found a higher rate of
      mechanical restraints at the TWMU. In 1997, the average length of stay was
      significantly higher at the TWMU (153 days) than at the BKR (52 days), but
      inpatients of the TWMU improved only slightly better with regard to global
      psychosocial functioning (GAF) and severity of illness (CGI). CONCLUSIONS: The
      revealed differences in treatment are likely due to differences in service
      provision and national practices in Germany and Japan and provide clues for
      quality improvements. The BADO is a useful tool for continuous quality management
      and an ongoing international exchange concerning psychiatric inpatient care.

PMID- 15864979
TI  - Clinical evaluation of combined spatial compounding and adaptive imaging in
      breast tissue.
AB  - When spatial compounding is applied to targets with significant acoustic velocity
      inhomogeneities, the correlation between speckle patterns of the images to be
      averaged decreases, thereby increasing the speckle reduction nominally obtained.
      Phase correction applied to these targets improves the coherence of the wavefield
      and restores image spatial frequencies. Combining these two modes can be used to
      effectively increase the contrast-to-noise ratio (CNR) of imaging targets and
      improve the general image quality of these targets over spatial compounding
      alone. This paper presents a clinical evaluation of combined spatial compounding
      and adaptive imaging in breast tissue and compares this combined technique to
      conventional imaging and to adaptive imaging and spatial compounding operating
      independently. Experiments were performed on a 1.75-D, 8 x 96 array attached to a
      commercially-available scanner. Cysts, microcalcifications and other breast
      structures were targeted in order to assess the impact of the combined mode on
      CNR, target width, target brightness and target peak-to-background ratio (PBR).
      In general, phase correction improved cyst CNR by 7.7%, decreased target width by
      18.7%, increased target brightness by 30.1% and increased PBR by 17.9%.
      Compounding alone, using three overlapping 9.71 mm subapertures, increased cyst
      CNR by 24.6%, but increased target width by 25.4% and decreased PBR by 13.2%.
      Combining both modes, however, increased cyst CNR by 32.6%, inappreciably
      increased target width by 1.1% and marginally decreased PBR by 2.8%. The increase
      in target brightness with this combined mode was 20.0%

PMID- 15864981
TI  - Influence of bright intramural echoes on estimates of ultrasonic attenuation from
      backscattered ultrasound in excised myocardium.
AB  - The purpose of this study was to quantitate the influence of bright intramural
      echoes on estimates of myocardial attenuation from analyses of backscattered
      ultrasound. To achieve this, M-mode image-based measurements of the inherent
      anisotropic properties of myocardial attenuation were performed on rotating
      myocardial specimens. The approach was to use a commercially-available ultrasonic
      imaging system to acquire M-mode images of 24 excised cylindrical specimens from
      six formalin-fixed lamb hearts for data analysis using a video signal analysis
      technique. As a control, through-transmission rf-based measurements were
      performed concurrently using a pair of focused, single-element ultrasonic
      transducers. We devised an objective approach to compensate M-mode results for
      the presence of bright intramural echoes that makes use of the rotational
      symmetry of the measurements. A comparison of the uncompensated and compensated
      estimates of attenuation shows that the effect of bright intramural echoes under
      the conditions of this study increases the average error in M-mode results by
      approximately 240% compared with that observed when such effects are minimized by
      compensation. For both uncompensated and compensated M-mode results, increased
      temporal averaging shows only a modest reduction in average error. These data
      suggest that for measurements of attenuation from backscattered ultrasound using
      M-mode images, the effects of bright intramural echoes can be a significant
      source of error despite increased temporal averaging and therefore may require
      compensation.

PMID- 15864980
TI  - Real-time 3D transesophageal echocardiography.
AB  - Transesophageal echocardiography (TEE) is an essential diagnostic tool in
      patients with poor transthoracic echocardiographic windows or when detailed
      imaging of structures distant from the chest wall is necessary. A real-time 3D
      TEE probe has been fabricated in our laboratory in order to increase the amount
      of information available during a transesophageal procedure. The 1 cm diameter
      esophageal probe utilizes a 2-dimensional, 5 MHz array at its tip with a 6.3 mm
      diameter aperture, including 504 active channels. The array has a periodic
      vernier geometry with an element pitch of 0.18 mm, built onto a multilayer
      flexible (MLF) interconnect circuit. In order to accommodate 504 channels within
      the device, a 1 m long Gore MicroFlat cable was utilized for wiring the MLF to
      the corresponding system connectors. Pulse-echo tests in a water tank have
      yielded a -6 dB bandwidth of 25.3%. Fully connected to the system through 3 m of
      cable, the probe shows an average 50 omega insertion loss of-85 dB with a
      standard deviation of 4 dB, as determined through pitch-catch measurements for a
      sampling of 10 elements. Using the completed 3D TEE probe with the Volumetrics
      Medical Imaging 3D scanner, real-time volumetric images of in vivo canine cardiac
      anatomy have been acquired, displaying atrial views, mitral valve function and
      interventional catheter guidance.

PMID- 15864982
TI  - [Osteoporosis: progress in its diagnosis and treatment].

PMID- 15864983
TI  - [Concept of osteoporosis and the purpose of its treatment].

PMID- 15864984
TI  - [Epidemiology of osteoporosis and its significance as a risk factor for
      fractures].

PMID- 15864985
TI  - [Therapeutic and social effects of osteoporosis and fractures].

PMID- 15864986
TI  - [Postmenopausal osteoporosis].

PMID- 15864987
TI  - [Osteoporosis of the aged].

PMID- 15864988
TI  - [Steroid-induced osteoporosis].

PMID- 15864989
TI  - [Osteoporosis caused by inactivity].

PMID- 15864991
TI  - [Diagnostic standard for osteoporosis].

PMID- 15864990
TI  - [Rheumatoid arthritis and osteoporosis].

PMID- 15864992
TI  - [Diagnosis of a fracture].

PMID- 15864993
TI  - [Determination of bone density].

PMID- 15864994
TI  - [Evaluation of osteoporosis by markers of bone metabolism].

PMID- 15864995
TI  - [Therapy of osteoporosis and EBM].

PMID- 15864996
TI  - [Treatment of osteoporosis: Vitamin D and calcium preparations].

PMID- 15864997
TI  - [Treatment of osteoporosis. Bisphosphonates].

PMID- 15864998
TI  - [Raloxifene for the treatment of osteoporosis].

PMID- 15864999
TI  - [Indications for hormone replacement therapy for osteoporosis and its possible
      drawbacks to be considered].

PMID- 15865000
TI  - [Wnt co-receptor LRP5 gene and osteoporosis].

PMID- 15865001
TI  - [New development related to osteoporosis. Parathyroid hormone (PTH)].

PMID- 15865002
TI  - [Treatment of osteoporosis in daily medical practice: discussion].

PMID- 15865003
TI  - [Herpes simplex virus encephalitis in pregnancy].

PMID- 15865004
TI  - [Rhabdomyolysis induced by ostraciid fish poisoing].

PMID- 15865005
TI  - [Severe alcoholic hepatitis resulting in liver transplantation: the first case in
      Japan].

PMID- 15865006
TI  - [Small cell lung cancer presenting as hemophagocytic syndrome].

PMID- 15865007
TI  - [Half pitch lower sound perception caused by carbamazepine].

PMID- 15865008
TI  - [Physiopathology and treatment of pulmonary alveolar proteinosis].

PMID- 15865009
TI  - [Treatment of hepatic diseases with bone marrow stem cell transplantation].

PMID- 15865010
TI  - [Gene abnormalities in Parkinson disease].

PMID- 15865011
TI  - [Diagnosis and attempt to treat nervous system diseases with magnetic
      stimulation].

PMID- 15865012
TI  - [New Development in inhalation therapy for COPD].

PMID- 15865013
TI  - [Definition and the diagnostic standard for metabolic syndrome--Committee to
      Evaluate Diagnostic Standards for Metabolic Syndrome].

PMID- 15865014
TI  - Postoperative pathophysiology and choice of incision.
AB  - In the few days following major surgical procedures, there are three main
      physiologic processes which are amenable to surgical management: restoration of
      fluid and electrolyte homeostasis, management of pain, and attention to
      gastrointestinal function. New information regarding optimizing the management of
      these processes is presented, which may accelerate recovery and give improved
      comfort following abdominal surgery. The type of incision used seems not to be a
      major factor in such recovery.

PMID- 15865015
TI  - Fast-track colonic surgery: status and perspectives.
AB  - Multi-modal rehabilitation with an emphasis on preoperative information,
      reduction of surgical stress responses, optimized dynamic pain relief with
      continuous epidural analgesia and early mobilization and oral nutrition may
      reduce hospital stay, morbidity, convalescence, and costs (fast-track surgery).
      Current results from fast-track colonic surgery suggest that postoperative
      pulmonary, cardiovascular, and muscle function are improved and body composition
      preserved as well as a normal oral intake of energy and protein can be achieved.
      Consequently, hospital stay is reduced to about 2-4 days, with decreased fatigue
      and need for sleep in the convalescence period. Despite a higher risk for
      readmissions, overall costs and morbidity seem to be reduced. Existing data from
      several institutions support the concept of fast-track colonic surgery to improve
      postoperative organ functions, thereby allowing for early rehabilitation with
      decreased hospital stay, convalescence, and costs. Further data are needed from
      multi-national institutions on morbidity, safety, and costs.

PMID- 15865016
TI  - Fast-track surgery: the Heidelberg experience.
AB  - Fast-track surgery is an interdisciplinary multimodal concept of minimally
      invasive surgery or new incision lines and "cutting old plaits" (e.g., the use of
      drains or tubes). It uses modern intraoperative anesthesia (e.g., fluid
      restriction) and analgesia, including new drugs and novel ways of administration
      (e.g., thoracic epidural analgesia) for postoperative pain relief, in combination
      with the immediate mobilization of the patient and early oral nutrition after the
      operation. This approach requires a cooperating team of motivated nurses,
      physiotherapists, anesthesiologists, and surgeons, in addition to continuous
      improvement of the processes involved. Moreover, extended patient education and
      information about the procedures and the expected time course are of the highest
      importance, as the active role of the patient is to be emphasized. This chapter
      describes the development and implementation of fast-track surgery in colorectal
      diseases at the Department of Surgery of the University Hospital of Heidelberg,
      Germany. Preliminary results of fast-track surgery suggest a significant and
      clear overall benefit for the patient. A shorter hospital stay and reduced
      systemic morbidity in addition to no increase in postoperative complications on
      an out-patient basis were found. However, to exclude a "bloody discharge" of the
      patients, thorough follow-up and quality control are mandatory. Although in the
      initial phase increased personnel care is necessary, in the new German
      reimbursement system with G-DRGs (German diagnosis-related groups) fast-track
      surgery seems to save resources in the long term.

PMID- 15865017
TI  - Rectal cancer: a compartmental disease. the mesorectum and mesorectal lymph
      nodes.
AB  - Even though the technique of total mesorectal excision has been widely used,
      there have been few detailed descriptions of the distribution of lymph nodes
      within the rectal mesentery. We describe the results of our anatomic study of
      lymph node size and distribution within the mesorectum and pelvic side-wall
      tissue using a fat-clearing solvent in seven male cadavers, and we used a similar
      technique to examine the mesorectum in a patient who underwent total mesorectal
      excision after preoperative chemoradiation for a uT3 rectal cancer. In both the
      cadavers and our patient, the majority of lymph nodes were located within the
      posterior upper two-thirds of the mesorectum. Few lymph nodes were located in the
      distal mesorectum or anteriorly. In the cadavers, the majority of lymph nodes
      were less than 3 mm in diameter. In the patient who had received preoperative
      chemoradiation, routine tissue processing yielded only four lymph nodes, whereas
      processing in fat-clearing solvent yielded 25 additional nodes. The majority of
      these nodes, in contrast to those observed in cadavers, were less than 1 mm in
      diameter. The majority of mesorectal lymph nodes were located within the upper
      two-thirds of the posterior mesorectum. Complete removal of nodes in this area
      may, in part, explain the superior results of total mesorectal excision with
      respect to local recurrence.

PMID- 15865018
TI  - The pathological assessment of total mesorectal excision: what are the relevant
      resection margins?
AB  - An accurate pathological reporting of rectal cancer specimens has important
      implications concerning patients' prognosis and further clinical management.
      Since locoregional recurrence and prognosis in rectal cancer is especially
      influenced by the extent of extramural tumor spread into the mesorectal
      lymphovascular fatty tissue, systematic investigation of the status of the
      circumferential mesorectal resection margin is a point of major importance to
      determine the completeness of tumor resection. Careful macroscopic assessment of
      the resection specimen should be performed to monitor the quality of mesorectal
      excision.

PMID- 15865019
TI  - Is the lateral lymph node compartment relevant?
AB  - Lateral pelvic lymphadenectomy is routinely performed in advanced lower rectal
      cancers by Japanese surgeons, whereas in the western world it has not progressed
      to a frequently performed technique. Claimed benefit for this extensive surgery
      is an improved locoregional control; on the other hand, low positive lateral
      lymph node yields, questionable prognostic significance, and high morbidity
      (urinary and sexual dysfunction) are main reasons against this procedure.
      Clinical results published on lateral lymphadenectomy in the literature are
      conflicting. Due to major improvements in local control and survival of rectal
      cancer patients mainly based on preoperative radiotherapy and total mesorectal
      excision (TME), only a few patients may profit from lateral lymph node
      dissection. This article gives an overview of the current status and the clinical
      relevance of the lateral lymph node compartment in rectal cancer surgery.

PMID- 15865020
TI  - Diagnostics of rectal cancer: endorectal ultrasound.
AB  - In rectal cancer, accurate preoperative staging is essential to adequately select
      patients for different therapeutic regimes. Endosonography has been proven to be
      an accurate staging modality in multiple prospective studies. A recent large
      retrospective study, however, has cast doubt on the actual accuracy of endorectal
      ultrasound for staging rectal cancer in everyday clinical routines. The results
      of endosonographic staging of rectal tumours over a period of 10 years at the
      Department of Surgery of the University of Heidelberg are presented. In a first
      time period, 424 patients with rectal cancer were staged by endosonography and
      the data recorded prospectively. The examinations were exclusively done by four
      surgeons with high experience and scientific interest in endosonography. The
      second time period comprises 332 patients with rectal tumours (including
      adenomas) having undergone endosonography by six different examiners after
      introduction of this staging method into the clinical routine. The data here were
      analysed retrospectively. Accuracy, sensitivity, specificity, and positive and
      negative predictive values were calculated for the T and N classifications for
      both series. In the second series, eight factors which have been postulated to
      influence staging accuracy in the literature were included in a regression
      analysis in order to identify relevant factors for staging inaccuracies. Accuracy
      for staging of the T classification was 81% in the first series versus 71.7% in
      the second series. In the regression analysis of the second series, status post
      chemoradiation proved to be the most significant factor for staging inaccuracy (p
      < 0.0002). When excluding all patients having undergone chemoradiation, the
      accuracy for staging of the T classification rose to 76%. A major problem of
      endosonography in this second series was overstaging; the T category was
      overestimated in 76 cases (22.9% of patients). The main error here was
      overstaging of adenomas as cancerous lesions (45.5% of all adenomas) and T2
      cancers as more advanced cancers (42.2% of all T2-cancers). When excluding the
      adenomas from this analysis, the accuracy increased to 73.5%. Accuracy for
      staging of the N classification was 76% in the first series versus 71% in the
      second series. Status post-chemoradiation again was a relevant factor (p <
      0.0003); when excluding these patients the accuracy increased to 73%. The
      accuracy of endosonography for rectal tumours decreases after introduction of the
      method into the everyday clinical routine. Nonetheless, apart from magnetic
      resonance imaging with an endorectal coil, rectal endosonography is still the
      most accurate staging modality for rectal tumours and allows adequate selection
      of patients for different therapeutic regimes. As the major problem of rectal
      endosonography is overstaging, more patients are likely to undergo overtreatment
      rather than undertreatment. Endosonography is inaccurate in staging patients
      having undergone chemoradiation.

PMID- 15865021
TI  - Preoperative staging of rectal cancer: the MERCURY research project.
AB  - The development of a surgical technique that removes the tumour and all local
      draining nodes in an intact package, namely total mesorectal excision (TME)
      surgery, has provided the impetus for a more selective approach to the
      administration of preoperative therapy. One of the most important factors that
      governs the success of TME surgery is the relationship of tumour to the
      circumferential resection margin (CRM). Tumour involves the CRM in up to 20% of
      patients undergoing TME surgery, and results in both poor survival and local
      recurrence. It is therefore clear that the importance of the decision regarding
      the use of pre-operative therapy lies with the relationship of the tumour to the
      mesorectal fascia. In addition, a high-spatial-resolution MRI technique will
      identify tumours exhibiting other poor prognostic features, namely, extramural
      spread >5 mm, extramural venous invasion by tumour, nodal involvement, and
      peritoneal infiltration. The potential benefits of a selective approach using MRI
      based selection criteria are evident. That is, over 50% of patients can be
      treated successfully with primary surgery alone without significant risk of local
      recurrence or systemic failure. Of the remainder, potentially dramatic
      improvements may be achieved through the use of intensive and targeted
      preoperative therapy aimed not only at reducing the size of the primary tumour
      and rendering potentially irresectable tumour resectable with tumour-free
      circumferential margins, but also at enabling patients at high risk of systemic
      failure to benefit from intensive combined modality therapy aimed at eliminating
      micrometastatic disease.

PMID- 15865022
TI  - Rectal cancer management: Europe is ahead.

PMID- 15865023
TI  - Teaching efforts to spread TME surgery in Sweden.
AB  - The whole infrastructure of rectal cancer treatment in Sweden has changed
      dramatically due to the awareness of the local recurrence rate, good surgical
      technique, and selective use of radiotherapy. Surgeons have been trained in a
      proper way, and it has been proven that the outcome has improved enormously in
      our country [14]. Due to repeated reports from the SRCR to each unit, it is
      possible for every surgeon to follow the process. It has been shown that the
      outcome for not only colon cancer but also rectal cancer has improved
      dramatically during the last 40 years, and there is a marked improvement in
      survival from approximately 40% in the early 1960s to almost 60% in the late
      1990s [15]. An interesting phenomenon is that the relative 5-year survival rate
      has, during the 5-year cohort, been better for patients with colon cancer
      compared to those with rectal cancer. For the last two 5-year cohorts in Sweden,
      1990-1995 and 1996-2000, the results for rectal cancer patients have improved,
      and in the most recent cohort, rectal cancer patients are actually doing better
      than colon cancer patients in terms of relative survival [16]. This increase has
      been interpreted to be a result of much better surgery, a more selective use of
      radiotherapy, but most of all an awareness of the results and focus on good
      auditing. This quality assurance and quality control of rectal cancer surgery is
      important and will be mandatory in the future for all units to not only know the
      results but also be able to present them in a way that patients can understand.
      We are facing a new generation of young patients who are familiar with the
      Internet and find all types of information before having surgery. It is obvious
      that only the best units will survive in such a competition, and the only way to
      be able to compete is to show good results within a good and validated population
      based quality registration, as is the situation for many different diseases in
      Sweden today. A tremendous change has been seen in our country over the last two
      decades, and it is in part a result of registration and quality auditing, where
      the results are displayed to the surgeons.

PMID- 15865024
TI  - Learning curve: the surgeon as a prognostic factor in colorectal cancer surgery.
AB  - The individual surgeon is an independent prognostic factor for outcome in
      colorectal cancer surgery. The surgeon's learning curve is therefore directly
      related to the patient's outcome. The exact shape of the learning curve, however,
      is unknown. The present study reviewed supervision, training/teaching,
      specialization, surgeon's caseload, and hospital's caseload as the five main
      surgeon- and hospital-related confounding factors for outcome, and examined their
      influence on the learning curve as well as their interactions and prognostic
      significance. All five confounding factors were related to outcome. The highest
      degree of evidence, however, was found for training/teaching (introduction of
      total mesorectal excision), specialization in colorectal surgery (special
      interest, board-certification, specialized colorectal cancer units), and the
      surgeon's caseload. Five surgeon- and hospital-related factors directly influence
      the surgeon's learning curve and are therefore rightly considered predictors of
      outcome in colorectal cancer surgery. Improvements in supervision,
      training/teaching, specialization, the surgeon's caseload, and the hospital's
      caseload will therefore translate into enhanced patient outcome.

PMID- 15865025
TI  - Surgical results of total mesorectal excision for rectal cancer in a specialised
      colorectal unit.
AB  - Our aim was to review the results of total mesorectal excision (TME) in a
      specialised colorectal unit. Perioperative and follow-up data were prospectively
      collected in a computerised database. A review of all the records was made. The
      morbidity rate was about 14%, and was higher in patients with coloplasty due to a
      higher anastomotic leak rate. The local recurrence rate was 2%, the distant
      metastasis rate was 11%, and both local and distant metastasis occurred in 4%.
      About 95% of recurrence occurred within 3 years. There was better bowel function
      in patients with a colonic J-pouch in the first 2 years after surgery, but the
      advantage disappeared thereafter. There were no differences in function between
      descending and sigmoid colonic J-pouches. TME in a specialised colorectal unit
      has low morbidity and mortality. Our procedure of choice is that of a sigmoid
      colon J-pouch anal anastomosis.

PMID- 15865026
TI  - Total mesorectal excision: the Heidelberg results after TME.
AB  - The introduction of the total mesorectal excision (TME) has changed the treatment
      of rectal cancer dramatically by reducing the local recurrence rate. We report
      the results of 208 patients undergoing a low anterior resection (LAR, n = 180) or
      abdominoperineal resection (APR, n = 28) with TME between 1 October 2001 and 30
      September 2003. No adjuvant therapy was administered to any patient; however, 108
      patients received neoadjuvant radiotherapy or radiochemotherapy. Since February
      2002, 51 patients underwent a short-course radiotherapy with 5x5 Gy prior to
      surgery in cases of a T3 tumor or positive lymph node in the preoperative CT-scan
      or endoanal ultrasound. Patients with a T4 tumor or T3 tumor close to the
      sphincter received radiochemotherapy. We discuss the results for mortality,
      morbidity, functional outcome, and overall survival between the LAR and APR
      groups. The mortality rate was 3% in the LAR and 0% in the APR group, whereas the
      morbidity was higher in the APR group. Anastomotic leakages occurred in eight
      patients (7%), and reoperations had to be performed in 14 LAR and four APR
      patients. After a median follow-up of 11 months, the overall survival was 93% for
      LAR and 89% for APR. To assess the functional outcome after TME, questionnaires
      were sent to all patients undergoing LAR and APR. In conclusion, the TME has
      become the gold standard for rectal cancer surgery. Neoadjuvant treatment
      modalities such as preoperative short term radiotherapy (5x5 Gy) or combined
      radiochemotherapy will most likely replace the adjuvant combined
      radiochemotherapy.

PMID- 15865027
TI  - Is local excision of T2/T3 rectal cancers adequate?
AB  - In selected patients, local excision of rectal cancer may be an alternative to
      radical surgery such as abdominoperineal excision of the rectum or anterior
      resection. Local excision carries lower mortality and morbidity, without the
      functional disturbance or alteration in body image that can be associated with
      radical surgery. There are several techniques of local therapy for rectal cancer,
      with most experience being available in transanal excision. Transanal endoscopic
      microsurgery is also used but experience with this newer technique is limited.
      Patient selection is the most important factor in successful local excision;
      however, specific criteria for selecting patients have not been universally
      accepted. Review of the published literature is difficult because of the
      variation in adjuvant therapy regimes and follow-up strategies, as well as
      results reported in terms of local recurrence and survival rates. There is
      increasing evidence to suggest that local excision should be restricted to
      patients with T1-stage rectal cancer without high-risk factors. The place for
      local excision in patients with T2 or high-risk T1 tumours requires prospective,
      randomised multicentre trials comparing radical surgery with local excision, with
      or without adjuvant therapy. Local excision for T3 tumours should be restricted
      to the palliative setting or patients unfit for radical surgery.

PMID- 15865028
TI  - Operative treatment of locally recurrent rectal cancer.
AB  - Few centres with varying regimens have published studies including more than 100
      patients on the treatment of locally recurrent rectal cancer. The results vary
      considerably. Thus there seems to be a need for more studies to establish the
      potential benefit of a more widespread treatment of these cancers. In total, 193
      patients had surgery for locally recurrent rectal cancers after preoperative
      irradiation 46-50 Gy in 2 Gy fractions. The patients were followed up and the
      data prospectively entered in a database. In 88 patients with primary low
      anterior resection, 3% had lower end of tumour located more than 2 cm above the
      anastomosis, 5% more than 2 cm below the anastomosis; 13% had exploratory
      laparotomy, 8% low anterior resections, the rest equally frequent abdomino
      perineal resections, Hartmann's operations, and tumour resections. Nearly half
      had resection of part of the pelvic wall. Hysterectomy was performed in 15% and
      cystoprostatectomy in 9%. Three patients had en bloc prostatectomy. R0 resections
      were achieved in 39%, R1 in 36%, and R2 or no resection in 25%. R0 stage was
      twice as often achieved after a primary low anterior resection as after abdomino
      perineal resections. The 30-days postoperative mortality was 1%. Postoperative
      morbidity was 48%, most frequently pelvic abscesses. Estimated 5-year survival
      was 18% for the total group. There was a statistically significant difference in
      survival and local re-recurrences between R0 / R1 and R2 stages. The results are
      discussed relative to recent studies. Patients in whom R0 resections can be
      achieved will benefit from the treatment, and probably patients with R1
      resections would also benefit. Such operations should possibly be performed in
      specialised centres as joint ventures between various surgical subspecialities.

PMID- 15865029
TI  - Laparoscopic TME: better vision, better results?
AB  - One of the most controversial discussions on laparoscopic surgery deals with the
      question of whether to apply this technique to malignant disease and specifically
      to rectal cancer. The four major issues are the adequacy of oncologic resection,
      recurrence rates and patterns, long-term survival and quality of life. There is
      evidence, from nonrandomized studies, suggesting that margins of excision and
      lymph node harvest achieved laparoscopically reached comparable results to those
      known from conventional open resection. Our own experience of laparoscopic
      surgery on rectal cancer is based on 52 patients treated with curative intent.
      Focusing on the postoperative long-term run, we gained the following results: The
      median age of patients was 66.7 years and ranged from 42-88. Anastomotic leakage
      was seen in 6.1% of cases. In a median follow-up of 48 months (36-136), we
      reached an overall 3-year survival rate of 93% and a 5-year survival rate of 62%.
      Local recurrence was 1.9%, distant metastasis occurred in 11.5% of cases. We saw
      no port-site metastasis. To evaluate functional results following laparoscopic
      surgery a matched pair analysis was carried out. Matching of patients after
      laparoscopic and conventional open surgery was performed according to sex, age,
      type of resection, time period of surgery, and stage of disease classified by
      UICC. Regarding bladder and sexual dysfunction, using the EORTC QLQ CR38 score we
      found no statistical significant difference between the examined groups. As far
      as can be seen, laparoscopic surgery in rectal carcinoma may achieve the same or,
      in selected patients, even better results than open surgery. However, at present
      no published study has shown much evidence. Many more studies are necessary to
      define the place of laparoscopic technique in rectal cancer surgery, regarding
      appropriate selection of patients and evaluating adjuvant or neoadjuvant
      treatment in combination with the laparoscopic approach.

PMID- 15865030
TI  - Laparoscopic TME-the surgeon's or the patient's preference.
AB  - Since laparoscopic surgery in rectal cancer was introduced ten years ago large
      patient collectives have been published by several authors in the meantime. The
      literature was carefully reviewed to analyse data on postoperative complications,
      long term prognosis and quality of life after laparoscopic surgery for rectal
      cancer to answer the question whether laparoscopic surgery is still just feasible
      or maybe has even reached the golden standard. The review showed that there is
      not a single prospectively randomized trial published comparing laparoscopic vs.
      open surgery for rectal cancer. It is clearly evident that until now the most
      laparoscopic series are published with patients selected according to criteria
      that vary significantly especially regarding the kind of procedures performed
      (anterior, low anterior, intersphincteric resections and abdomino-perineal
      excision), other demographic items like gender, body mass index, eventual prior
      laparotomies, emergencies and tumor related characteristics like tumor stage or T
      categories. At the moment any data concerning outcome from prospectively
      randomized trials comparing laparoscopic versus open surgery for rectal cancer
      are missing. Therefore, there is more speculation and belief concerning the true
      quality of laparoscopic surgery. The review in the literature only indicates,
      that laparoscopic surgery for rectal cancer is feasible. To prove the potential
      advantage of laparoscopic surgery in rectal cancer randomized trials are
      essential. If a surgeon discusses laparoscopic surgery outside a randomized
      trial, he should go through a questionnaire, presented in the paper which
      reflects the present situation without any proven advantage and not available
      long term results and should leave a final decision to the patient.

PMID- 15865031
TI  - Laparoscopic total mesorectal excision-the Turin experience.
AB  - Improved local control and survival rates in the treatment of rectal cancer have
      been reported after total mesorectal excision (TME). We performed an analysis of
      TME for rectal cancer by laparoscopic approach during a prospective nonrandomized
      trial. A prospective consecutive series of 98 laparoscopic total mesorectal
      excision (LTME) procedures for low and mid-rectal tumors. All patients had a
      sphincter-saving procedure. Case selection, surgical technique, and clinical and
      oncological results were reviewed. The distal limit of rectal neoplasm was on
      average 5.4 cm (range 3-12) from the anal verge. The mean operative time was
      192.5 min (range 125-360). The conversion rate was 18.4%. The mean postoperative
      stay was 11.6 days (range 4-61). The 30-day mortality rate was 1% (1/98) and the
      overall postoperative morbidity was 18.4% including 10 anastomotic leakages.
      Concerning long-term oncological results, we evaluated 93 (94.8%) patients with a
      median follow-up of 46.3 months (range 12-132). During this period, 15.1% (14/93)
      died of cancer and 7.5% (7/93) are alive with metastatic disease. The port-site
      metastases rate was 2.1% (2/93). The locoregional pelvic recurrence rate was 2.1%
      (2/93): 1 stage II at 12 months and 1 stage III at 18 postoperative months,
      respectively. LTME is a feasible but technically demanding procedure (18.4%
      conversion rate). Our series confirms the safety of the procedure, while
      oncological results are at present comparable to the open published series with
      the limitation of a short follow-up period. Further studies and possibly
      randomized series will be necessary to evaluate long-term clinical outcome in
      cancer patients.

PMID- 15865032
TI  - Evacuation of neorectal reservoirs after TME.
AB  - Colon pouch reconstruction after deep rectal resection is functionally superior
      to straight colorectal/anal anastomosis. However, stool evacuation difficulties
      could jeopardize the functional benefit of neorectal reservoirs. Beside the well
      proven colon J-pouch, the transverse coloplasty pouch may represent a viable
      alternative. We examined evacuation and functional outcome after total mesorectal
      excision and transverse coloplasty pouch reconstruction. Thirty consecutive
      patients with cancer of the middle and distal third of rectum underwent a total
      mesorectal excision. In all patients, reconstruction was performed with a
      transverse coloplasty pouch. Pouch and anastomosis were checked by Gastrografin
      enema postoperatively. Eight months after surgery, video defecography, anal
      manometry and pouch volumetry were performed and the patients were interviewed
      according to a standardized continence questionnaire. Rectal resection and
      reconstruction with transverse coloplasty pouch anastomosis could be performed in
      all patients. No insufficiency of the pouch occurred. In the follow-up, no
      patient had difficulties to evacuate the pouch, none of these patients needed
      enemas or suppositories to facilitate defecation. All patients were continent for
      solid stools. Twenty-five of 27 patients had up to three bowel movements per day.
      Patients with reduced pelvic floor movement in the defecography proved more
      likely to suffer from urgency, fragmented evacuation and incontinence. Transverse
      coloplasty pouch reconstruction after total mesorectal excision is not associated
      with stool evacuation problems. Urgency and incontinence, which are rarely seen
      after this type of reconstruction, correlate with impaired pelvic floor movement
      rather than with pouch size or anal sphincter tonus.

PMID- 15865033
TI  - Long-term functional results after straight or colonic J-pouch coloanal
      anastomosis.
AB  - Proctectomy followed by straight coloanal anastomosis (CAA) often results in poor
      functional outcome known as the anterior resection syndrome. It is now based on
      evidence that a colonic J-pouch CAA improves outcome in the first 2 years. We
      assessed the very late functional outcome of CAA patients with or without a
      pouch. These results show that the functional benefit of the J-pouch anastomoses
      is sustained over the very long term.

PMID- 15865034
TI  - Urinary and sexual function after total mesorectal excision.
AB  - The autonomous pelvic nerves are in close contact to the visceral pelvic fascia
      that surrounds the mesorectum. The concept of total mesorectal excsion (TME) in
      rectal cancer treatment has led to a substantial improvement of autonomous pelvic
      nerve preservation. Consecutively, this highly precise and sharp dissection
      technique under direct vision reduces the problem of accidental bladder
      denervation from 50-60% with conventional rectal cancer surgery to less than 20%
      with TME and the problem of postoperative impotence from 70-100% to less than
      30%. The learning curve in this technically demanding procedure plays a major
      role with regard to a satisfying nerve preservation. The laparoscopic approach
      for TME allows to obtain similarly favorable results with regard to postoperative
      urogenital function, at least for tumors situated in the middle and upper third
      of the rectum, compared with open surgery. The present paper describes and
      depictures in detail the anatomy and the pathophysiology of autonomic pelvic
      nerves, the surgical technique for nerve preservation and gives a short overview
      of the results in the literature including own data.

PMID- 15865035
TI  - Functional results of the colon J-pouch versus transverse coloplasty pouch in
      Heidelberg.
AB  - Within the last 20 years various achievements have been made in the treatment of
      rectal cancer, improving survival and quality of life of rectal cancer patients.
      Especially the introduction of the total mesorectal excision (TME) and the use of
      modern staplers, making anastomoses possible in the deep pelvis, have increased
      our ability to cure more and more low rectal cancers by sphincter-preserving low
      anterior resections. Consequently, the interest in functional results after
      rectal reservoir reconstruction has increased significantly. Various randomized
      controlled trials have shown that the colon J-pouch (CJP) as a rectal reservoir
      reconstruction leads to better early functional results compared to the straight
      coloanal anastomosis (CAA). However, 30% of the patients with CJP faced late
      evacuation problems, requiring the chronic use of enemas or laxatives. This rate
      could be decreased to 10% by shortening the limb of the CJP from 8-10 cm to 5-6
      cm. The transverse coloplasty pouch (TCP) was developed to provide early
      functional results comparable to the CJP, while avoiding these late evacuation
      problems. We report the early postoperative and functional results of 106
      patients undergoing low anterior resections with TCP due to rectal cancer between
      October 2001 and the end of September 2003. Furthermore, we report on a single
      center randomized controlled trial to compare the new TCP technique with the gold
      standard technique of CJP, which we started in October 2002. The objectives were
      to compare the two pouch reconstruction techniques in terms of morbidity,
      mortality and functional results.

PMID- 15865036
TI  - Indications for neoadjuvant long-term radiotherapy.
AB  - If radiotherapy is considered in the management of a rectal cancer, there is very
      strong evidence supporting preoperative settings. To avoid treatment to cases
      where surgery alone is enough, exact preoperative staging with MRI is crucial.

PMID- 15865037
TI  - Neoadjuvant radiotherapy and radiochemotherapy for rectal cancer.
AB  - Combined radiochemotherapy is the recommended standard postoperative therapy for
      patients with stage II and III rectal cancer in the USA and in Germany. During
      thelast decade, substantial progress has been made in treatment modalities:
      surgical management currently includes a broad spectrum of operative procedures
      ranging from radical operations such as abdominoperineal resections to innovative
      sphincter-preserving techniques. Specialized groups have reported excellent local
      control rates with total mesorectal excision (TME) alone without the addition of
      neoadjuvant or adjuvant treatment. New and improved radiation techniques using
      conformal radiotherapy as well as innovative chemotherapy schedules and
      combinations (capecitabine, oxaliplatin, irinotecan) of chemotherapy may have the
      potential to further increase the therapeutic benefit of (neo-)adjuvant
      treatment. Moreover, the basic issue of timing of radiotherapy-preoperative
      versus postoperative-within a multimodality regimen is currently being addressed
      in prospective trials. Evidently, the current monolithic approach established by
      studies conducted more than a decade ago, to either apply the same schedule of
      postoperative radiochemotherapy to all patients with UICC stage II and III rectal
      cancer or to give preoperative short-course radiation according to the Swedish
      concept for all patients with resectable rectal cancer irrespective of tumor
      stage and treatment goal (e.g., sphincter preservation), need to be questioned.

PMID- 15865038
TI  - Adjuvant radiochemotherapy for rectal cancer.

PMID- 15865039
TI  - Intraoperative radiotherapy for rectal carcinoma.

PMID- 15865040
TI  - Indications and effect on survival of standard chemotherapy in advanced
      colorectal cancer.
AB  - Since the introduction of combined systemic chemotherapy with 5-folinic-acid (FA)
      and/or oxaliplatin or irinotecan, the median survival in patients with advanced
      colorectal cancer has increased to more than 20 months. Novel agents in so-called
      targeted therapies such as monoclonal antibodies will further increase these
      excellent survival data in the near future.

PMID- 15865041
TI  - New chemotherapeutic strategies in colorectal cancer.
AB  - Since colorectal cancer is the second most prevalent cancer worldwide, its
      treatment remains a major challenge for researchers, gastroenterologists and
      oncologists. Despite curative resections, half of all patients diagnosed with
      colorectal cancer die because of their underlying disease. Integral
      chemotherapeutic components of standard regimens are 5-fluorouracil (5-FU), its
      modulation by folinic acid and irinotecan or oxaliplatin. All these drugs
      sequentially given have results in terms of median overall survival of more than
      20 months in the palliative treatment of advanced colorectal cancer. Oral
      fluoropyrimidines, currently under clinical investigation, are likely to
      substitute continuous 5-FU. Inhibitors of growth factor receptors or their
      signaling may further prolong disease-free and overall survival rates.
      Preliminary evidence exists that improved adjuvant and neoadjuvant chemotherapy
      strategies may further improve the prognosis, mainly because more patients are
      able to go for primary or secondary surgery with curative intent.

PMID- 15865042
TI  - Active specific immunotherapy in colon cancer.
AB  - Colorectal cancer is one of the leading causes of cancer-related mortality. After
      a series of clinical trials, the adjuvant 5-FU-based chemotherapy has established
      a definitive role in the management of stage III colon cancer. While the precise
      role for chemotherapy in stage II disease remains under investigation, less toxic
      treatment modalities such as active specific immunotherapy (ASI) have emerged as
      potentially attractive alternatives. In a randomized trial it was demonstrated
      that ASI, using autologous tumor cells and BCG, had a significant clinical
      benefit in the adjuvant treatment of stage II colon cancer. In addition, it was
      found that the delayed-type cutaneous hypersensitivity reactions (DTH) against
      autologous cells correlated significantly with survival, confirming its
      suitability for immunomonitoring. Nowadays, 5-FU-based chemotherapy is a standard
      treatment for stage III colon cancer and because there is preclinical evidence
      for synergism between chemotherapy and ASI, we performed a phase II study to
      investigate whether the combined treatment with 5-FU and ASI is tolerable and
      feasible. We demonstrated that 5-FU treatment hardly affected the DTH response
      against autologous tumor cells and that the combination treatment was well
      tolerated. A randomized phase III trial is now warranted to show that the
      combination of ASI and chemotherapy is superior to chemotherapy alone.

PMID- 15865043
TI  - Radiofrequency ablation in metastatic disease.
AB  - The liver is the most common site of metastas from colorectal cancer. Hepatic
      metastases are the major cause of morbidity and mortality in those patients.
      Surgical resection provides the greatest potential for cure in patients with
      secondary liver tumors but can be offered to only a small number of patients (5%
      20%). In selected patients image-guided radiofrequency ablation (RFA) takes over
      the role as curative treatment option, especially in patients who are technically
      not eligible for surgery. Technical aspects, criteria for patient selection,
      aspects concerning follow-up imaging and results of percutaneous radiofrequency
      ablation in liver metastases from colorectal cancer are discussed.

PMID- 15865045
TI  - Transformation of fruit trees. Useful breeding tool or continued future prospect?
AB  - Regeneration and transformation systems using mature plant material of woody
      fruit species have to be achieved as a necessary requirement for the introduction
      of useful genes into specific cultivars and the rapid evaluation of resulting
      horticultural traits. Although the commercial production of transgenic annual
      crops is a reality, commercial genetically-engineered fruit trees are still far
      from common. In most woody fruit species, transformation and regeneration of
      commercial cultivars are not routine, generally being limited to a few genotypes
      or to seedlings. The future of genetic transformation as a tool for the breeding
      of fruit trees requires the development of genotype-independent procedures, based
      on the transformation of meristematic cells with high regeneration potential
      and/or the use of regeneration-promoting genes. The public concern with the
      introduction of antibiotic resistance into food and the restrictions due to new
      European laws that do not allow deliberate release of plants transformed with
      antibiotic-resistance genes highlight the development of methods that avoid the
      use of antibiotic-dependent selection or allow elimination of marker genesfrom
      the transformed plant as a research priority in coming years.

PMID- 15865044
TI  - Enhancing gene targeting efficiency in higher plants: rice is on the move.
AB  - Meeting the challenge of routine gene targeting (GT) in higher plants is of
      crucial interest to researchers and plant breeders who are currently in need of a
      powerful tool to specifically modify a given locus in a genome. Higher plants
      have long been considered the last lineage resistant to targeting technology.
      However, a recent report described an efficient method of T-DNA-mediated targeted
      disruption of a non-selectable locus in rice [Terada et al., Nat Biotechnol 20:
      1030-1034 (2002)]. Though this study was an obvious breakthrough, further
      improvement of GT frequencies may derive from a better understanding of the
      natural mechanisms that control homologous recombination (HR) processes. In this
      review, we will focus on what is known about HR and the factors which may hamper
      the development of routine GT by HR in higher plants. We will also present the
      current strategies envisaged to overcome these limitations, such as expression of
      recombination proteins and refinements in the design of the transformation
      vector.

PMID- 15865046
TI  - In situ analysis of Raidd-beta-galactosidase fusion gene expression in transgenic
      mouse midgestation embryos.
AB  - Apoptosis and differentiation are tightly intertwined processes occurring at
      organ formation and remodelling during embryonic development. RAIDD (receptor
      interacting protein [RIP]-associated ICH-1/CED-3-homologous protein with a death
      domain), a dual-domain adaptor protein has been shown to mediate the recruitment
      of CASPASE-2 to tumour necrosis factor receptor-1 (TNF-R1) signalling complex
      through RIP kinase. However, Raidd overexpression studies suggest that apart from
      the established role in apoptosis, Raidd may have an additional function in cell
      differentiation. In this study, we could not generate Raidd null adult mice
      suggesting that lack of function of Raidd might be embryonic lethal. Thus, to
      elucidate the role of Raidd during mouse embryogenesis when the processes of
      organogenesis are most dynamic, we studied the Raidd expression pattern in
      midgestation mouse embryos. We generated Raidd+/- transgenic mice with a reporter
      transgene encoding the bacterial Beta-galactosidase (beta-gal) under the control
      of Raidd promoter. During the midgestation period (E8.5-E12.5), Raidd is
      expressed in developing organs derived from the ectoderm such as lens, structures
      of the inner ear and the fourth brain ventricle in regions where differentiation
      takes place implicating Raidd role in this process. In addition, Raidd expression
      was found in developing mesenchyme organs like heart and kidney and in the
      endothelial lining of the midgut at the time when profound morphological changes
      take place in these organs. In developing heart and kidney Raidd expression
      patterns overlapped with known zones of cell death suggesting Raidd may be
      involved in apoptosis-mediated remodelling. The observed lethality of mice
      targeted at both Raidd alleles and Raidd expression patterns during midgestation
      period strongly suggest that Raidd plays an important role in mammalian
      development.

PMID- 15865047
TI  - Transgenic resistance to Cymbidium mosaic virus in Dendrobium expressing the
      viral capsid protein gene.
AB  - A Taiwan isolate of Cymbidium mosaic virus (CymMV-CS) was isolated from infected
      Cymbidium sinesis Willd. The cDNA of the capsid protein (CP) gene was synthesized
      and sequenced. Alignment of this CP gene with other reported CPs revealed
      homologies of 92-98% at the nucleotide level and 98-99% at the amino acid level.
      To generate virus-resistant varieties, the CymMV-CS CP gene was transformed into
      Dendrobium protocorms through particle bombardment. Transformants were selected
      on medium supplemented with 20 mg/L hygromycin and the presence of the transgene
      was confirmed by polymerase chain reaction, Southern, Northern and Western blot
      analyses. Transgenic Dendrobium harboring the CymMV CP gene expressed a very low
      level of virus accumulation four months post-inoculation with CymMV, as detected
      by ELISA. The transgenic plants exhibited much milder symptoms than the non
      transgenic plants upon challenge with CymMV virions.

PMID- 15865048
TI  - Non-invasive imaging of a transgenic mouse model using a prostate-specific two
      step transcriptional amplification strategy.
AB  - Non-invasive assessment of transgenic animals using bioluminescence imaging
      offers a rapid means of evaluating disease progression in animal models of
      disease. One of the challenges in the field is to develop models with robust
      expression to image repetitively live intact animals through solid tissues. The
      prostate-specific antigen (PSA) promoter is an attractive model for studying gene
      regulation due to its hormonal response and tissue-specificity permitting us to
      measure signaling events that occur within the native tissues. The use of the
      GAL4-VP16 activator offers a powerful means to augment gene expression levels
      driven by a weak promoter. We have used a two-step transcriptional amplification
      (TSTA) system to develop a transgenic mouse model to investigate the tissue
      specificity and developmental regulation of firefly luciferase (fl) gene
      expression in living mice using bioluminescence imaging. We employed an enhanced
      prostate-specific promoter to drive the yeast transcriptional activator, GAL4
      VP16 (effector). The reporter construct carries five Gal4 binding sites upstream
      of the fl gene. We generated a transgenic mouse model using a single vector
      carrying the effector and reporter constructs. The transgenic mice show prostate
      specific expression as early as three weeks of age. The bioluminescence signal in
      the prostate is significantly higher than in other organs. We also demonstrate
      that blocking androgen availability can downregulate the fl expression in the
      prostate. The transgenic mice display normal physical characteristics and
      developmental behavior, indicating that the high level of GAL4 driven expression
      is well tolerated. These findings suggest that the GAL4-VP16 transactivator can
      be used to amplify reporter gene expression from a relatively weak promoter in a
      transgenic mouse model. The transgenic TSTA model in conjunction with other
      transgenic cancer models should also help to detect and track malignancies. The
      strategies developed will be useful for transgenic research in general by
      allowing for amplified tissue specific gene expression.

PMID- 15865049
TI  - Unexpected effects of chitinases on the peach-potato aphid (Myzus persicae
      Sulzer) when delivered via transgenic potato plants (Solanum tuberosum Linne) and
      in vitro.
AB  - With the aim of producing insect-resistant potato plants, internode explants of
      Solanum tuberosum L. cv. Desiree were transformed with an Agrobacterium strain
      C58pMP90 containing an insect (Phaedon cochleariae: Coleoptera, Chrysomelidae)
      chitinase gene and the neomycin phosphotransferase (nptII) gene as selectable
      marker, both under the control of the viral CaMV 35S promoter. Three transformed
      potato lines (CH3, CH5 and CH25) exhibiting the highest chitinolytic activities
      were selected for feeding experiments with the peach-potato aphid, Myzus persicae
      (Sulzer), under controlled photoperiod and temperature conditions. Aphids fed on
      transgenic potato plants showed a reduced pre-reproductive period and an enhanced
      daily fecundity. Transgenic potato lines did not affect nymphal mortality, but
      improved several biological parameters related to aphid population's growth.
      Artificial diets were used to provide active (1, 10, 100 and 500 microg ml(-1))
      and inactive (500 microg ml(-1)) bacterial (Serratia marcescens) chitinase to M.
      persicae. These compounds increased nymph survival at all active chitinase doses
      when compared to the control diet, while inactive chitinase did not. Although the
      pre-reproductive period was slightly shortened and the daily fecundity slightly
      higher, active and inactive chitinase provided as food led a reduction from 1 to
      1.5 day population's doubling time. Therefore chitinase activity was responsible
      for the probiotic effects on aphids. Our results question the relevance of a
      chitinase-based strategy in the context of potato culture protection.

PMID- 15865050
TI  - A 7.1 kbp beta-myosin heavy chain promoter, efficient for green fluorescent
      protein expression, probably induces lethality when overexpressing a mutated
      transforming growth factor-beta type II receptor in transgenic mice.
AB  - The roles of transforming growth factor-beta (TGFbeta) in heart or skeletal
      muscle development and physiology are still the subject of controversies. Our aim
      was to block, in transgenic mice, the TGFbeta signalling pathway by a dominant
      negative mutant of the TGFbeta type II receptor fused to the enhanced green
      fluorescent protein (TbetaRII-KR-EGFP) under the control of a 7.1 kbp mouse beta
      myosin heavy chain (betaMHC) promoter to investigate the roles of TGFbeta in the
      heart and slow skeletal muscles. First, we generated two transgenic lines
      overexpressing EGFP under the control of the 7.1 kbp betaMHC promoter. In
      embryos, EGFP was detectable as early as 7.5 days post coitum. In embryos,
      newborns and adults, EGFP was expressed mainly in the cardiac ventricles and in
      slow skeletal muscles. EGFP expression was intense in the bladder but weak in the
      intestines. In contrast to the endogenous betaMHC promoter, the activity of the
      7.1 kbp betaMHC promoter in the transgene was not repressed after birth and
      remained high in adult transgenic mice. We obtained two founders with the
      transgene comprising the TbetaRII-KR-EGFP sequence under the control of the 7.1
      kbp betaMHC promoter. These founders were generated at a very low frequency and
      expressed barely detectable levels of TbetaRII-KR-EGFP mRNA. Our failure to
      obtain transgenic lines overexpressing the dominant negative receptor suggests
      that the blocking of the TGFbeta signalling pathway in the heart and slow
      skeletal muscles could be embryonically lethal. To conclude, the 7.1 kbp betaMHC
      promoter directs high levels of transgene expression in the cardiac ventricles
      and in slow skeletal muscles of the mouse. Analysis of the consequences of the
      blocking of the TGFbeta signalling pathway in the heart will require the use of
      tissue specific means of conditional gene invalidation.

PMID- 15865051
TI  - Transgenic cucumbers harboring the 54-kDa putative gene of Cucumber fruit mottle
      mosaic tobamovirus are highly resistant to viral infection and protect non
      transgenic scions from soil infection.
AB  - Cucumber fruit mottle mosaic tobamovirus (CFMMV) causes severe mosaic symptoms
      and yellow mottling on leaves and fruits and, occasionally, severe wilting of
      cucumber (Cucumis sativus L.) plants. No genetic source of resistance against
      this virus has been identified in cucumber. The gene coding for the putative 54
      kDa replicase gene of CFMMV was cloned into an Agrobacterium tumefaciens binary
      vector, and transformation was performed on cotyledon explants of a
      parthenocarpic cucumber cultivar. R1 seedlings were screened for resistance to
      CFMMV by symptom expression, back inoculation on an alternative host and ELISA.
      From a total of 14 replicase-containing R1 lines, eight resistant lines were
      identified. Line 144--homozygous for the putative 54-kDa replicase gene--was
      immune to CFMMV infection by mechanical and graft inoculation, and to root
      infection following planting in CFMMV-infested soil. A substantial delay of
      symptom appearance was observed following infection by three additional cucurbit
      infecting tobamoviruses. When used as a rootstock, line I44 protected susceptible
      cucumber scions from soil infection by CFMMV. This paper is the first report on
      protection of a susceptible cultivar against a soil-borne viral pathogen, by
      grafting onto a transgenic rootstock.

PMID- 15865053
TI  - Omega-3 fatty acids and neuropsychiatric disorders.
AB  - Epidemiological evidence suggests that dietary consumption of the long chain
      omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
      commonly found in fish or fish oil, may modify the risk for certain
      neuropsychiatric disorders. As evidence, decreased blood levels of omega-3 fatty
      acids have been associated with several neuropsychiatric conditions, including
      Attention Deficit (Hyperactivity) Disorder, Alzheimer's Disease, Schizophrenia
      and Depression. Supplementation studies, using individual or combination omega-3
      fatty acids, suggest the possibility for decreased symptoms associated with some
      of these conditions. Thus far, however, the benefits of supplementation, in terms
      of decreasing disease risk and/or aiding in symptom management, are not clear and
      more research is needed. The reasons for blood fatty acid alterations in these
      disorders are not known, nor are the potential mechanisms by which omega-3 fatty
      acids may function in normal neuronal activity and neuropsychiatric disease
      prevention and/or treatment. It is clear, however, that DHA is the predominant n
      3 fatty acid found in the brain and that EPA plays an important role as an anti
      inflammatory precursor. Both DHA and EPA can be linked with many aspects of
      neural function, including neurotransmission, membrane fluidity, ion channel and
      enzyme regulation and gene expression. This review summarizes the knowledge in
      terms of dietary omega-3 fatty acid intake and metabolism, as well as evidence
      pointing to potential mechanisms of omega-3 fatty acids in normal brain
      functioning, development of neuropsychiatric disorders and efficacy of omega-3
      fatty acid supplementation in terms of symptom management.

PMID- 15865052
TI  - Expression of endogenous and exogenous growth hormone (GH) messenger (m) RNA in a
      GH-transgenic tilapia (Oreochromis niloticus).
AB  - We have previously produced transgenic fish from crosses between a wild-type
      female tilapia (Oreochromis niloticus) and a G transgenic male. This line of
      growth-enhanced tilapia carries a single copy of a chinook salmon (s) growth
      hormone (GH) gene spliced to an ocean pout antifreeze promoter (OPA-FPcsGH) co
      ligated to a carp beta-actin/lacZ reporter gene construct, integrated into the
      tilapia genome. Because little is known about the expression sites of transgenes,
      we have characterised the gene expression patterns of sGH and tilapia (t)GH in
      transgenic tilapia using a newly established real-time PCR to measure the
      absolute mRNA amounts of both hormones. The sGH gene, which was expected to be
      expressed mainly in liver, was also found to be expressed in other organs, such
      as gills, heart, brain, skeletal muscle, kidney, spleen, intestine and testes.
      However, in pituitary no sGH mRNA but only tGH mRNA was found. Tilapia GH mRNA in
      wild-type pituitary amounted to 226 +/- 30 pg/microg total RNA but in transgenics
      only to 187 +/- 43 pg/microg total RNA. Liver exhibited the highest level of sGH
      mRNA (8.3 +/- 2.5 pg/microg total RNA) but the extrahepatic sites expressed
      considerable amounts of sGH mRNA ranging from 4.1 +/- 2.0 pg/microg total RNA in
      gills to 0.2 +/- 0.08 pg/microg total RNA in kidney. The widespread expression of
      the sGH gene is assumed to be due to the tissue specificity of the type III AFP
      gene promoter. It is assumed that our transgenic experiments, which in contrast
      to some other approaches caused no obvious organ abnormalities, mimick the GH
      expression during ontogeny. Because sGH mRNA is expressed both in liver and in
      extrahepatic sites it may not only promote secretion and release of liver-derived
      (endocrine) IGF-I leading to an overall growth enhancement but also stimulate IGF
      I expression within the different organs in a paracrine/autocrine manner and,
      thus, further promote organ growth.

PMID- 15865054
TI  - Evaluation of dog semen quality after slow (biological freezer) or rapid
      (nitrogen vapours) freezing.
AB  - Three ejaculates were collected from each of five dogs. After initial evaluation,
      the sperm-rich fractions were diluted to 100 x 10(6) spermatozoa x mL(-1) in two
      steps with an egg yolk-TRIS extender containing a final concentration of 5%
      glycerol and 0.5% Equex STM paste. Half of the 0.5 mL straws obtained from each
      ejaculate were frozen on nitrogen vapours (4 cm above the liquid surface) ("rapid
      freezing"), while the other half was frozen in a biological freezer at a rate of
      0.5 degrees C x min(-1) between 5 degrees C and -10 degrees C and of 8 degrees C
      x min(-1) between -10 degrees C and -60 degrees C, followed by immersion in
      liquid nitrogen ("slow freezing"). After an average storage of 30 days, the
      straws were thawed in a water-bath at 37 degrees C for 1 min. Progressive
      motility was subjectively estimated hourly for 8 h on semen incubated at 38
      degrees C. Immediately after thawing and after 2 h of incubation, motility
      parameters were also measured by a motility analyser. Sperm membrane function and
      chromatin stability were assessed immediately post-thaw, using the hypo-osmotic
      swelling test and acridine orange staining, respectively. Slow freezing
      significantly improved total post-thaw motility, which showed a slower decline
      over time, although spermatozoal average path and straight line velocity were
      lower compared to the fast rate. Also the number of intact membrane spermatozoa
      was significantly higher in slow-frozen samples while the proportion of
      spermatozoa with single-stranded DNA was minimal after both freezing procedures.

PMID- 15865055
TI  - Dietary protein restriction during lactation in primiparous sows with different
      live weights at farrowing: I. Consequences on sow metabolic status and litter
      growth.
AB  - The hypothesis that the restriction of dietary protein during lactation has
      different impacts on sow metabolic status and milk production according to body
      weight was evaluated. From 5-months of age until farrowing, the gilts were fed to
      achieve body weights of 180 or 240 kg at farrowing. At this time, 38 sows were
      assigned to one of three groups: " 180 kg" sows not restricted in dietary protein
      during lactation (180CP); "180 kg" restricted in protein (180LP), or "240 kg"
      sows restricted in protein (240LP). Catheters were fitted in the jugular vein of
      24 sows and serial blood samples were collected 1 d before and 1 d after weaning.
      Amongst the protein-restricted animals, heavy sows (240LP) had a smaller appetite
      than light sows in early lactation, resulting in lower energy and protein intakes
      in the 240LP than in the 180LP sows. Body protein losses were 8, 11 and 13.5% of
      calculated body protein mass at farrowing in the 180CP, 180LP and 240LP sows,
      respectively. At the end of lactation, IGF-I concentrations were lower in the
      180LP than in the sows from the other groups, probably because of the uncoupling
      between GH and IGF-I secretions. Low IGF-I concentrations likely promote lean
      tissue mobilization. Glucose and insulin profiles suggested an insulin resistance
      state in the 240LP sows compared with the 180LP sows, which may explain, at least
      in part, the lower feed intake and body reserve mobilization in these sows.
      Plasma pre- and post-prandial concentrations of amino acids in late lactation
      differed among the three treatment groups. Throughout lactation, litters from the
      180LP and 240LP sows had a slower growth rate than litters from sows which were
      not restricted, suggesting that endogenous protein mobilization throughout
      lactation does not completely compensate for a low protein intake.

PMID- 15865056
TI  - Dietary protein restriction during lactation in primiparous sows with different
      live weights at farrowing: II. Consequences on reproductive performance and
      interactions with metabolic status.
AB  - The hypothesis that the restriction of dietary protein during lactation has
      different impacts on reproductive performance in light and heavy sows at
      farrowing was investigated, as well as the relationships between reproductive
      parameters and sow metabolic data. At farrowing, 38 primiparous sows were
      assigned to one of three groups: sows weighing 180 kg not restricted in dietary
      protein during lactation (180CP); sows weighing 180 or 240 kg restricted in
      protein (180LP and 240LP). Twenty-four sows were catheterized and serial blood
      samples were collected 1 d before and 1 d after weaning. The sows were
      inseminated at the first estrus after weaning and slaughtered at d 30 of
      gestation. Protein restriction reduced the proportion of sows that returned to
      estrus within 8 d after weaning in the 180LP sows (P < 0.03), but not in the
      240LP sows. It also induced a reduction in ovulation rate in the 180LP sows (P <
      0.05) and, to a lesser extent, in the 240LP sows (P = 0.12). When the sows were
      categorized according to return to estrus (WOI < or = 8 or > 8 d), basal and mean
      concentrations of LH increased after weaning only in sows with a short WOI. Sows
      with a delayed estrus exhibited a higher ratio of plasma tyrosine to large
      neutral amino acids (AA, P < 0.01). In conclusion, large body reserves at
      farrowing buffer, at least in part, the detrimental effect of a strongly negative
      nitrogen balance on reproduction. We suggest that the alteration of AA profiles
      induced by dietary protein restriction and body protein loss alters LH secretion
      via modifications of the neurotransmitters involved in GnRH secretion.

PMID- 15865057
TI  - Effects of exercise during growth and alternative rearing systems on muscle
      fibers and collagen properties.
AB  - Muscle characteristics, and particularly fiber type frequency and collagen
      properties, may be a source of variation in eating meat quality. Expanded space
      allowance in alternative breeding systems theoretically increases animal physical
      activity during growth. This review deals with effects of endurance training and
      spontaneous exercise in large areas in- and out-doors, on muscle characteristics
      in rabbits and pigs, two species of agronomic interest, and rats. Endurance
      training induces a fast-to-slower transition in myofiber contractile
      characteristics, following the IIB -> IIX -> IIA -> I transformation sequence.
      These changes are accompanied by a greater ability to transport fatty acids
      intracellularly, and (or) by enhanced activities of the mitochondrial reference
      enzymes. Newly synthesized heat-soluble collagen may be observed in the recruited
      muscles after endurance training in rats. Depending on the experiments (stocking
      density, ambient temperature, gender, and muscles), area allowance in- or out-of
      doors, does not affect fiber type frequency compared with conventional systems or
      results in a lower proportion of type IIB/X fibers at the benefit of slower
      twitch fibers. Muscle lipids and collagen content are generally not modified by
      expanded indoor area, however, a higher proportion of non-soluble collagen may be
      observed in free-range animals in doors compared with confined ones. It is
      impossible to state a general rule for lipid stores and collagen properties in
      animals reared out-of-doors. Therefore, exercise studies are unsuitable to
      predict adaptative responses in muscle characteristics to alternative outdoor
      rearing systems, and in fine meat quality.

PMID- 15865058
TI  - Effect of genotype and overfeeding on lipid deposition in myofibres and
      intramuscular adipocytes of breast and thigh muscles of ducks.
AB  - We conducted a study to evaluate the effects of genotype (Muscovy, Pekin and
      their crossbred, hinny and mule) and overfeeding (14 days from 12 weeks of age)
      on lipid deposition in myofibres and intramuscular adipocytes of breast and thigh
      muscles of ducks. Birds of the four genotypes were also reared contemporaneously
      with a growing diet distributed ad libitum. Muscle samples (Pectoralis major and
      Sartorius) were collected at 14 weeks of age on 8 ducks per treatment. The muscle
      fibre typing, the total lipid and triglyceride contents in myofibres and the
      relative surface occupied by adipocytes on the cross-sectional area of the
      muscles were determined by histological and image analysis. Overfeeding induced a
      marked increase of body weight but had no significant effect on the muscle
      weight, the cross-sectional area (CSA) of myofibres and the muscle typology. In
      muscles, overfeeding induced a large accumulation of lipids, mainly in adipocytes
      whose relative surface increased 1.5 fold in P. major and 2.1 fold in Sartorius
      and an increase in triglyceride content of fast twitch oxydo-glycolytic and
      glycolytic fibres in P. major only (+ 37 and + 16% respectively). Genotype had no
      significant effect on the muscle typology. By comparison with the other
      genotypes, Muscovy ducks exhibited the highest body weight, the highest muscle
      weight which could partly be explained by the highest fibre CSA and the lowest
      intramuscular fat content in adipocytes and myofibres (only fast twitch oxydo
      glycolytic fibres in P. major). We observed the reverse situation for the Pekin
      ducks. The crossbred ducks always presented intermediate values except for body
      weight.

PMID- 15865059
TI  - An early stimulation of solid feed intake slightly influences the morphological
      gut maturation in the rabbit.
AB  - The impact of dietary factors on the gut morphological maturation is poorly
      documented in rabbits. The weights of the digestive segments as well as the
      morphology of villi and crypts along the small intestine were analysed weekly
      from day 14 till day 49, in two rabbit groups weaned at either 21 (W21 group, n =
      12 litters) or 35 days (W35 group, n = 12 litters) of age. From 21 till 35 days,
      the W21 group ate 57% more solid feed than the W35 group (P < 0.01), and
      presented slighter body weights from day 28 till day 49 (-9%, P < 0.05). Tissue
      weights of the empty digestive segments, as expressed relative to the body
      weights, were higher in the W21 than in the W35 group from day 28 till day 49 (P
      < 0.001), whereas absolute tissue weights appeared similar (except for the
      proximal colon). From day 28 to day 49, small intestinal villi grew in height and
      surface area (P < 0.05) whereas the crypts deepened. Villous height followed a
      proximo-distal decreasing gradient from the duodenum to the ileum (P < 0.05) from
      day 28 onward. The villous height to width ratio changed with the beginning of
      significant solid feed intake: from a thin shape until day 21, villi became wider
      from day 28 on. The effect of weaning age on mucosal morphology was
      insignificant, except for the jejunal crypts whose surface area and depth were
      higher in the W21 group. The present results showed that morphological changes in
      the digestive tract of young rabbits were weakly influenced by an early
      stimulation of solid feed intake.

PMID- 15865060
TI  - Generation of multiple pharmacophore hypotheses using multiobjective optimisation
      techniques.
AB  - Pharmacophore methods provide a way of establishing a structure activity
      relationship for a series of known active ligands. Often, there are several
      plausible hypotheses that could explain the same set of ligands and, in such
      cases, it is important that the chemist is presented with alternatives that can
      be tested with different synthetic compounds. Existing pharmacophore methods
      involve either generating an ensemble of conformers and considering each
      conformer of each ligand in turn or exploring conformational space on-the-fly.
      The ensemble methods tend to produce a large number of hypotheses and require
      considerable effort to analyse the results, whereas methods that vary
      conformation on-the-fly typically generate a single solution that represents one
      possible hypothesis, even though several might exist. We describe a new method
      for generating multiple pharmacophore hypotheses with full conformational
      flexibility being explored on-the-fly. The method is based on multiobjective
      evolutionary algorithm techniques and is designed to search for an ensemble of
      diverse yet plausible overlays which can then be presented to the chemist for
      further investigation.

PMID- 15865061
TI  - Docking studies on NSAID/COX-2 isozyme complexes using contact statistics
      analysis.
AB  - The selective inhibition of COX-2 isozymes should lead to a new generation of
      NSAIDs with significantly reduced side effects; e.g. celecoxib (Celebrex) and
      rofecoxib (Vioxx). To obtain inhibitors with higher selectivity it has become
      essential to gain additional insight into the details of the interactions between
      COX isozymes-and NSAIDs. Although X-ray structures of COX-2 complexed with a
      small number of ligands are available, experimental data are missing for two well
      known selective COX-2 inhibitors (rofecoxib and nimesulide) and docking results
      reported are controversial. We use a combination of a traditional docking
      procedure with a new computational tool (Contact Statistics analysis) that
      identifies the best orientation among a number of solutions to shed some light on
      this topic.

PMID- 15865062
TI  - Comparison of substructural epitopes in enzyme active sites using self-organizing
      maps.
AB  - This paper presents a new algorithm to compare substructural epitopes in protein
      binding cavities. Through the comparison of binding cavities accommodating well
      characterized ligands with cavities whose actual guests are yet unknown, it is
      possible to draw some conclusions on the required shape of a putative ligand
      likely to bind to the latter cavities. To detect functional relationships among
      proteins, their binding-site exposed physicochemical characteristics are
      described by assigning generic pseudocenters to the functional groups of the
      amino acids flanking the particular active site. The cavities are divided into
      small local regions of four pseudocenters having the shape of a pyramid with
      triangular basis. To find similar local regions, an emergent self-organizing map
      is used for clustering. Two local regions within the same cluster are similar and
      form the basis for the superpositioning of the corresponding cavities to score
      this match. First results show that the similarities between enzymes with the
      same EC number can be found correctly. Enzymes with different EC numbers are
      detected to have no common substructures. These results indicate the benefit of
      this method and motivate further studies.

PMID- 15865063
TI  - Quantitative structure-activity relationships of mutagenic activity from quantum
      topological descriptors: triazenes and halogenated hydroxyfuranones (mutagen-X)
      derivatives.
AB  - The mutagenic activity of 23 triazenes and, in a different set, of 24 halogenated
      hydroxyfuranones (MX derivatives) is quantitatively related to new features of
      contemporary molecular wave functions. Nowadays affordable computers are powerful
      enough to rapidly generate geometry-optimised ab initio wave functions at HF/3
      21G*, HF/6-31G* and B3LYP/6-311 + G(2d,p) level for all molecules. The bonds of a
      common molecular skeleton are described by their ab initio bond lengths and local
      properties provided by the theory of quantum chemical topology (QCT). The
      chemometric analysis involves two types: one to generate a statistically
      validated quantitative model, and one to isolate the active center. In the former
      a genetic algorithm (GA) selects bond descriptors in order to optimise the cross
      validation error, q2, followed by a full partial least squares (PLS) analysis,
      which also yields randomisation statistics. In the latter type principal
      components (PCs) are constructed from the original bond descriptors and their
      variables important to the projection (VIPs) are plotted in a histogram. This
      analysis suggests a preferred mechanistic pathway for the initial hydroxylation
      of the triazenes, an issue that has remained ambiguous so far. In the case of the
      hydroxyfuranones the proposed method aids the elucidation of a mechanistic
      ambivalence.

PMID- 15865064
TI  - Conformational analysis of methylphenidate: comparison of molecular orbital and
      molecular mechanics methods.
AB  - Methylphenidate (MP) binds to the cocaine binding site on the dopamine
      transporter and inhibits reuptake of dopamine, but does not appear to have the
      same abuse potential as cocaine. This study, part of a comprehensive effort to
      identify a drug treatment for cocaine abuse, investigates the effect of choice of
      calculation technique and of solvent model on the conformational potential energy
      surface (PES) of MP and a rigid methylphenidate (RMP) analogue which exhibits the
      same dopamine transporter binding affinity as MP. Conformational analysis was
      carried out by the AM1 and AM1/SM5.4 semiempirical molecular orbital methods, a
      molecular mechanics method (Tripos force field with the dielectric set equal to
      that of vacuum or water) and the HF/6-31G* molecular orbital method in vacuum
      phase. Although all three methods differ somewhat in the local details of the
      PES, the general trends are the same for neutral and protonated MP. In vacuum
      phase, protonation has a distinctive effect in decreasing the regions of space
      available to the local conformational minima. Solvent has little effect on the
      PES of the neutral molecule and tends to stabilize the protonated species. The
      random search (RS) conformational analysis technique using the Tripos force field
      was found to be capable of locating the minima found by the molecular orbital
      methods using systematic grid search. This suggests that the RS/Tripos force
      field/vacuum phase protocol is a reasonable choice for locating the local minima
      of MP. However, the Tripos force field gave significantly larger phenyl ring
      rotational barriers than the molecular orbital methods for MP and RMP. For both
      the neutral and protonated cases, all three methods found the phenyl ring
      rotational barriers for the RMP conformers/invertamers (denoted as cte, tte, and
      cta) to be: cte, tte > MP > cta. Solvation has negligible effect on the phenyl
      ring rotational barrier of RMP. The B3LYP/6-31G* density functional method was
      used to calculate the phenyl ring rotational barrier for neutral MP and gave
      results very similar to those of the HF/6-31G* method.

PMID- 15865065
TI  - Molecular genetic tumor markers in non-small cell lung cancer.
AB  - Not only serum tumor markers, such as carcinoembryonic antigen (CEA), squamous
      cell carcinoma antigen (SCC) and carbohydrate antigen (CA) 125, but also serum
      growth factors have been examined to evaluate tumor stages and to predict the
      recurrence and metastasis in patients with non-small cell lung cancer (NSCLC) (1
      5). In recent years, the analysis of the genome and proteome has advanced
      remarkably. An array of molecular genetic tumor markers (MGTMs) have been
      identified based on the biological characterization of tumors, such as tumor
      development, growth, invasion and metastasis. Molecular genetic tumor marker
      research has also entered a new era, since comprehensive gene profile analysis
      using cDNA microarrays and comprehensive protein expression analysis using
      proteomics technology have been developed. On the other hand, the frequency of
      lung cancer patients with which various tumor markers are associated is
      increasing in Japan (6-8). This paper reviews MGTMs characteristic of lung cancer
      and clarifies the clinical usefulness and applications of MGTM for cancer
      treatment.

PMID- 15865066
TI  - Identification of serum proteins related to adverse effects induced by docetaxel
      infusion from protein expression profiles of serum using SELDI ProteinChip
      system.
AB  - BACKGROUND: For the development of quick and easy methods for screening and
      identifying treatment-responsive proteins, we determined the protein expression
      profile of the serum after docetaxel infusion using a surface-enhanced laser
      desorption/ionization time-of-flight mass spectroscopy (SELDI TOF-MS) system.
      MATERIALS AND METHODS: Blood from breast cancer patients was collected before and
      4, 8, 24 and 48 hours after docetaxel infusion. The protein expression profile
      was determined by a SELDI TOF-MS system. The relative expression levels of target
      proteins were compared during the time-course after docetaxel injection. RESULTS:
      We identified two representative proteins with molecular weights of 7790 Da and
      9285 Da. The 7790 Da protein was high molecular weight kininogen, and the 9285 Da
      protein was apolipoprotein A-II. These two proteins had similar expression
      patterns in 5 patients, except one patient who experienced severe, acute, adverse
      effects. CONCLUSION: These results suggest that protein expression profiles
      determined by SELDI TOF-MS represent useful data for the identification of
      treatment-responsive proteins.

PMID- 15865067
TI  - Immunohistochemical analysis of EGFR and HER-2 in patients with metastatic
      squamous cell carcinoma of the skin.
AB  - BACKGROUND: Metastatic squamous cell carcinoma (SCC) of the skin often raise
      difficult therapeutic problems. Few data are available about the expression of
      EGFR and HER-2 in SCC of the skin. Overexpression of EGFR and of HER-2 proteins
      has been reported. The purpose of this study was to investigate the expression of
      EGFR and HER-2 in a series of metastatic SCC of the skin. PATIENTS AND METHODS:
      EGFR and HER-2 expression was studied by immunochemistry on 13 specimens of
      metastatic recurrence and on 2 primary lesions of these tumours. RESULTS: EGFR
      had a strong membranous expression in all specimens. HER-2 was weakly expressed
      in 4 specimens, with a membrane expression in 2 cases. CONCLUSION: In the present
      study, EGFR was overexpressed in all samples of metastatic SCCs of the skin.
      Therefore, these metastatic tumours appear to be suitable targets for treatment
      with tyrosine kinase inhibitors. Additional studies are warranted to establish
      whether or not HER-2 is expressed in SCC of the skin.

PMID- 15865068
TI  - Sequential administration of epirubicin and paclitaxel for advanced breast
      cancer. A phase I randomised trial.
AB  - Forty-six previously untreated patients with advanced breast cancer were eligible
      for the present randomised phase I study. It aimed to evaluate the toxicity and
      activity of a therapeutic sequence with epirubicin on day 1 followed by
      paclitaxel on day 2 (sequence A) or the reverse sequence, ie., paclitaxel on day
      1 followed by epirubicin on day 2 (sequence B). The starting doses of epirubicin
      and paclitaxel, administered either according to sequence A or B, (level 1
      cohort) were 90 mg/m2 and 175 mg/m2, respectively. Per cohort of 3 patients, the
      dose of paclitaxel was increased by 25 mg/m2 (levels 2 and 4) and of epirubicin
      by 10 mg/m2 (levels 3 and 5). Treatment was repeated with 3-week intervals. The
      maximal tolerated dose (MTD) was achieved at level 1 in sequence B (paclitaxel
      first) and level 3 (epirubicin 100 mg/m2 followed by paclitaxel 200 mg m2) in
      sequence A. Dose limiting toxicity (DLT) was neutropenia (+/- febrile) in both
      sequences. Cardiac events occurred in 28% of the patients; significant decrease
      in left ventricular ejection function (LVEF) was observed in 8/33 and in 2/13
      patients in sequence A and B, respectively. This was associated with 5 and 1
      cardiac heart failure (CHF), respectively. In 43 evaluable patients, 10 CR and 25
      PR were observed (overall response rate 81%). In the 20 patients with locally
      advanced disease (LABC), the respective numbers were 7 CR and 11 PR; in the 23
      metastatic (MBC) patients, 3 CR and 14 PR were recorded. The median survival of
      the both groups was not reached at 33 + months. In conclusion , the combination
      of epirubicin and paclitaxel has significant activity in breast cancer. The
      recommended sequence of both drugs in combination therapy, mainly to avoid
      neutropenia, is epirubicin day 1 followed by paclitaxel on day 2. Cardiac
      toxicity remains problematic in either sequence of administration.

PMID- 15865069
TI  - Cancer in first degree relatives of Latin American women with cervical cancer. A
      pilot study.
AB  - BACKGROUND: Cervical cancer is the most frequent cancer of women in Latin
      America, being strongly associated with infection by certain human papillomavirus
      (HPV) types. Familial cancer clustering can be due to interactions between
      infectious agents and host genes. MATERIALS AND METHODS: A cancer-related family
      history of first degree relatives was elicited in 335 women with invasive
      cervical cancer (probands) and in 335 women without cancer (controls) in
      Honduras, Peru and Uruguay, and the frequency of reported familial cancers among
      the relatives was compared between proband and control relatives. RESULTS: The
      mean age at the time of interview was 49.8 years for the probands and 50.1 years
      for the controls (NS). 3852 proband relatives had 114 primary cancers of the
      following major localisations: 22 uterus, 16 lung, 12 stomach and 64 others. 3333
      control relatives had 101 primary cancers of the following major localizations:
      18 uterus, 13 stomach, 12 breast, 11 intestinal, 10 lung and 37 others. The
      frequency of all cancer diagnosis among proband relatives was similar to the
      frequency among control relatives (odds ratio= 1.01; 95% confidence interval:
      0.69-1.47). Nine haemolymphatic malignancies were reported among proband
      relatives versus 2 in control relatives (odds ratio=3.46; 95% confidence
      interval: 0.74-16.29). CONCLUSION: All cancer combined did not appear to be more
      frequent in first degree relatives of women with cervical cancer diagnosis, but
      haemolymphatic malignancies, a minor part of the cancer burden, may be
      overrepresented in relatives of women with cervical cancer, pointing to a
      pathogenic role of familial e.g. hereditary, immunosuppression.

PMID- 15865070
TI  - Clinical trial of photodynamic therapy using acridine orange with/without low
      dose radiation as new limb salvage modality in musculoskeletal sarcomas.
AB  - Most patients with musculoskeletal sarcoma do not recover satisfactory limb
      function after limb salvage surgery. To achieve satisfactory improvement of limb
      function, we developed a unique surgical modality of photodynamic therapy using
      acridine orange (AO-PDT) and clinically applied it to patients with
      musculoskeletal sarcomas. Ten patients with primary musculoskeletal sarcomas were
      enrolled in the study. Of these, 6 had primary malignant soft tissue sarcoma and
      4 had primary malignant bone tumor. In the AO-PDT procedure, intralesional or
      partially marginal tumor excision was initially conducted and microscopic
      curettage of the remnant tumor, which emitted green fluorescence under blue
      excitation after local administration of 1microg/ml AO solution, was performed
      using a fluorescence surgical microscope. Subsequently, blue light illuminated
      there for 10 minutes. The surgical wound was closed, followed by immediate X-ray
      irradiation of the resected area with 5 Gy in 5 out of 10 patients to enhance the
      effect of AO-PDT. The follow-up of the patients ranged from 24 to 48 months. All
      the patients (AO-PDT alone: 5, AO-PDT with 5-Gy radiation: 5) are alive; only one
      patient showed local recurrence of the tumor. The recurrence rate was 10%. None
      of the 5 patients treated by AO-PDT with radiation developed local tumor
      recurrence. The limb function in all the patients, except for one, recovered to
      the level before surgery. None of the patients clinically showed any local or
      systemic complications. AO-PDT may be a promising new limb salvage modality for
      preservation of excellent limb function in patients with musculoskeletal sarcoma.

PMID- 15865071
TI  - Expression of dihydropyrimidine dehydrogenase, thymidylate synthase, p53 and p21
      in metastatic liver tumor from colorectal cancer after 5-fluorouracil-based
      chemotherapy.
AB  - BACKGROUND: The expression of genes thought to be related to 5-FU
      chemosensitivity has been extensively investigated. However, little data is
      available on the expression patterns of these genes after chemotherapy. PATIENTS
      AND METHODS: We investigated the expression of four genes, DPD, TS, p53 and p21,
      in the metastatic liver lesions obtained from colorectal cancer patients who had
      been treated with hepatic arterial infusions of 5-fluorouracil(5-FU)-based
      chemotherapy. RESULTS: Expression of DPD, TS and p53 in the metastatic liver
      lesions was significantly higher in the chemotherapy-response group than in the
      no response group. In the response group, viable cancer cell nests were seen in
      confined spaces surrounded by fibrous tissue. It was of interest that these
      cancer cells in the response group showed conspicuous immunoreactivity of DPD, TS
      and p53. CONCLUSION: An analysis of genes involved in 5-FU sensitivity revealed
      that surviving tumor cells exhibited resistance characteristics, indicating that
      the chemotherapy regimen should be altered, even in partially responding cases,
      unless the response is pathologically complete.

PMID- 15865072
TI  - Macrocytic anemia during low-dose cisplatin and 5-Fluorouracil through implanted
      infusion port for unresectable hepatobilliary malignancies.
AB  - The efficacy of continuous arterial infusion chemotherapy through a
      subcutaneously implanted port has been reported with less adverse effects than
      systemic chemotherapy in hepatobilliary malignancies. However, macrocytic anemia
      is sometimes seen during this therapy. In 25 patients (22 with hepatocellular
      carcinoma, 3 with cholangiocellular carcinoma) treated with cisplatinum
      (10mg/day) and 5-Fluorouracil (5-FU) (250 mg/day), the frequency of anemia and
      its etiologies were evaluated. Moreover, the two groups ("anemia" and "no anemia"
      group) were compared with their backgrounds. Nine cases (36%) showed macrocytic
      anemia without any evident etiologies during therapy. The cumulative appearance
      rate of anemia was 19% at 12 weeks and 51% at 18 weeks. The Child-Pugh score or
      Japanese integrated staging (JIS) score were significantly higher in the "anemia"
      group than that in the "no anemia" group. CONCLUSION: Attention should be paid to
      slow progressive macrocytic anemia during low-dose cisplatinum and 5-FU,
      especially in patients with advanced liver cirrhosis.

PMID- 15865073
TI  - S100A2 overexpression is frequently observed in esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: We previously detected that deltaNp63, a human p53 homologue, is an
      oncogene amplified in squamous cell carcinomas (SCC) including esophageal SCC.
      Subsequently, we examined global patterns of gene expression in cancer cells
      following deltaNp63 gene introduction using an oligonucleotide microarray
      approach. We identified S100A2, a Ca2+-binding protein, as a novel downstream
      mediator of deltaNp63. MATERIALS AND METHODS: In this study, we examined S100A2
      expression in esophageal SCC cell lines and primary SCCs using Northern analysis.
      RESULTS: We found that 2 out of 8 (25%) cell lines and 14 out of 30 primary
      esophageal cancers (47%) showed S100A2 gene overexpression compared to paired
      normal tissues. To examine a possible relationship between S100A2 overexpression
      and clinicopathological features, we proceeded with statistical analysis. S100A2
      overexpression was significantly-associated with higher age in esophageal SCC
      (p=0.0434). Interestingly, S100A2-overexpressing cancers showed a trend toward
      preferentially developing lymph node metastases and distant metastases (p=0.111
      and 0.178, respectively). CONCLUSION: These results suggested that S100A2 might
      be related to the progression of esophageal SCC.

PMID- 15865074
TI  - A new staging system for colorectal carcinoma with liver metastasis.
AB  - PURPOSE: The prognosis of colorectal carcinoma (CRC) with liver metastasis varies
      from case to case. A standardized classification system for evaluation of the
      prognosis and the treatment is needed. Therefore, we developed a new staging
      system for CRC with liver metastasis (HM-stage) based on the survival data.
      PATIENTS AND METHODS: We evaluated 148 CRC patients with liver metastasis treated
      between 1985 and 1999. Prognostic factors were identified based on a multivariate
      analysis. According to the final prognostic factors and hazard ratios, we defined
      the HM- stage. RESULTS: Three factors, including extent of liver metastasis,
      depth of tumor invasion and peritoneal metastasis, were identified to be the
      final prognostic factors. These factors were then assigned points. The patients
      were classified as being HM-stage I to IV by the sum total. The median survival
      time for each HM-stage were 37 months for HM-stage I, 23 months for II, 10 months
      for III and 7 months for IV respectively. A significant difference among each
      stage was recognized (p<0.0001). CONCLUSION: This new staging system for CRC with
      liver metastasis is simple and should be clinically useful for both estimation of
      the prognosis and evaluation of the therapy in patients.

PMID- 15865075
TI  - Phase 1/11 study of bi-weekly irinotecan plus cisplatin in the treatment of
      advanced gastric cancer.
AB  - OBJECTIVES: To conduct a phase I/II study of irinotecan with cisplatin to
      establish a recommended dose, and assess the safety, efficacy and feasibility of
      this regimen in unresectable advanced or recurrent gastric cancer. PATIENTS AND
      METHODS: In the phase I portion of the study, patients received a fixed dose of
      cisplatin (30 mg/m2) with escalating doses of irinotecan, ranging from 30 mg/m2
      to 70 mg/m2, on days 1 and 15. In the phase II portion of the study, 40 patients
      were evaluated for response and safety at the recommended dose. RESULTS: Eighteen
      patients were enrolled in the phase I study. Dose-limiting toxicity (diarrhea and
      neutropenia) appeared at the irinotecan dose of 70 mg/m2. Therefore, the
      recommended irinotecan dose was 60 mg/m2. In the phase II study, 40 patients
      received cisplatin (30 mg/m2) plus irinotecan (60 mg/m2). Twenty-five out of 40
      patients had received prior chemotherapy. The median number of cycles was 3.5.
      The response rate was 32.5% (13/40) overall, and 53.3% (8/15) in patients without
      prior chemotherapy. The median time to tumor progression (TTP) was 162 days. The
      median survival time was 288 days. Four patients (10%) developed grade 4
      neutropenia and 3 patients (7.5%) developed grade 4 anemia. The only observed non
      hematological toxicity at grade 3 or higher was diarrhea, seen in 2.5% (1/40) of
      the patients. CONCLUSION: Bi-weekly administration of irinotecan and cisplatin is
      safe and active for the management of unresectable advanced or recurrent gastric
      cancer.

PMID- 15865076
TI  - Comparison of ante- and post-mortem PSA levels for epidemiological studies.
AB  - BACKGROUND: Valuable correlations could be made between serum prostate specific
      antigen (PSA) and prostate histopathology by the use of autopsy sampling if post
      mortem PSA data were informative. However, PSA forms and levels in autopsy sera
      have not been investigated. MATERIALS AND METHODS: Paired ante- and post-mortem
      sera were collected for a series of cases. Total and free PSA levels in each were
      determined and compared. These PSA data were correlated with corresponding
      changes in serum electrolyte levels. RESULTS: Total PSA levels were similar in
      ante- and post-mortem sera if autopsy blood was drawn by approximately 24 hours
      following the time of death. Free PSA levels, however, were increased
      approximately two-fold in most post-mortem sera analyzed. Increases in the serum
      electrolytes potassium, magnesium and phosphate correlated positively with
      increases in free PSA. CONCLUSION: Total PSA levels in ante- and post-mortem sera
      were comparable. Free PSA levels had approximately doubled by autopsy, but may be
      normalized in relation to increases in serum electrolyte levels. The use of
      autopsy prostates and PSA data would avoid diagnostic bias from use of clinical
      material and permit extensive analysis to be carried out, which is not normally
      feasible with live subjects.

PMID- 15865077
TI  - The role of tumour budding at the front of invasion and recurrence of rectal
      carcinoma.
AB  - The presence of "tumour budding", ie. single cancer cells, or a nest of poorly-
      differentiated cells at the front of invasion, in bowel cancer appears to be a
      new histopathological indicator of increased aggressiveness of colorectal
      carcinoma. The aim of this work was a retrospective evaluation of the front of
      invasion in preoperative biopsies of patients with rectal carcinoma (T1) and an
      analysis of the relationship between tumour budding and metastases or recurrence
      of the tumour at the site of resection. PATIENTS AND METHODS: The study was
      performed based on material obtained before and during surgical treatment of 34
      patients with cancer of the colon. Tissue was obtained directly following tumour
      resection, fixed in 10% formaldehyde and embedded in paraffin blocks using a
      routine method by melting with paraffin at a temperature of 56 degrees C. These
      samples were then routinely stained with haemotoxylin and eosin and underwent a
      histopathological evaluation, with particular attention being paid to the front
      of invasion of the tumour. RESULTS: Tumour budding (TB) at the front of invasion
      was found in 12 out of 34 patients. Statistical analysis showed a correlation
      between TB and the histological type of tumour, the presence of lymph node
      metastases, distant metastases and recurrence of the tumour in post-operative
      scars. CONCLUSION: The results suggest the usefulness of evaluating TB at the
      front of invasion as an additional prognostic indicator in rectal carcinoma.

PMID- 15865078
TI  - Determination of optimal dosage for nedaplatin based on pharmacokinetic and
      toxicodynamic analysis.
AB  - Nedaplatin is a platinum derivative anticancer drug. To determine its target AUC
      in cancer patients, the relationship between platinum AUC and hematological
      toxicity after administration of nedaplatin was analyzed. The data for plasma
      unbound platinum concentration, platelet (PLT) and white blood cell (WBC) counts
      were retrospectively obtained from 108 courses administered to 74 Japanese adult
      cancer patients. PLT and WBC decreased significantly after nedaplatin
      administration. The results of linear regression analysis suggested that the
      relative reduction ratio of PLT significantly correlated with AUC after
      nedaplatin administration and the relationship was not affected by the dosing
      course of nedaplatin nor the combination of other cancer drugs. From these
      findings, it became possible to determine the target AUC based on the pre-dose
      value of PLT and the tolerable or target nadir of PLT after nedaplatin
      administration. By using a simple formula to predict the individual platinum
      clearance of nedaplatin from a patient's renal function, it is possible to
      determine the optimal dose for individuals by taking into consideration the
      adequate maximum tolerable AUC and individual platinum clearance.

PMID- 15865079
TI  - Optimal sampling and limited sampling strategies for estimation of unbound
      platinum AUC after nedaplatin infusion.
AB  - The aim of this study was to determine the optimal sampling design for empirical
      Bayesian forecasting for nedaplatin, and also to develop a simple formula for
      estimating the area under the plasma concentration-time curve (AUC) of platinum
      which relates to hematological toxicity after nedaplatin dosing using limited
      sampling points. Plasma unbound platinum concentration data were retrospectively
      collected from 27 courses administered to 20 Japanese adult patients. To
      determine the optimal sampling points, 1 - 5 data point(s) were selected with all
      combinations and clearance in each patient was estimated by the empirical
      Bayesian method. As measures for the Bayesian predictive performance, mean
      prediction error and root mean squared error were estimated. These indices
      suggested that the sampling time(s) of 4 hours in case of the one-point sampling
      gives better estimates for individual clearance. As for the limited sampling
      strategy, a simple formula to calculate AUC, AUC = 0.039x dose + 11.6 x Cp4h -
      0.88, was obtained, where Cp4h is the concentration at 4 hours after the end of
      infusin. These results should be helpful for adjusting dosage to achieve the
      target AUC.

PMID- 15865080
TI  - A combination phase I study of weekly paclitaxel and doxifluridine in advanced
      gastric cancer patients.
AB  - BACKGROUND: Preclinical studies have shown that paclitaxel and doxifluridine can
      act synergistically without overlapping toxicity for the treatment of advanced
      gastric cancer. The objectives of this study were to determine the maximum
      tolerated dose (MTD), the dose-limiting toxicity and the recommended Phase II
      dose for this drug combination. PATIENTS AND METHODS: Patients with
      histologically confirmed gastric cancer were eligible for the study. The
      paclitaxel dose (days 1, 8, 15) was augmented with a fixed dose of for treatments
      (1-3). doxifluridine (533 mg/m2, 5 days/week) on a 28-day cycle. RESULTS:
      Eighteen patients were enrolled. The MTD was not reached until the highest dose
      level. One patient had Grade 3 myelosuppression. The responses of the 13 suitable
      patients included 1 complete response and 5 partial responses. CONCLUSION:
      Although the MTD level could not be definitively which is a established, upon
      consideration of the lengthy administration time and the effectiveness, the
      recommended Phase II dose of paclitaxel was concluded to be 80 mg/m2 in
      combination with doxifluridine at 533 mg/m2.

PMID- 15865081
TI  - A phase II multicentric trial of S-1 combined with 24 h-infusion of cisplatin in
      patients with advanced gastric cancer.
AB  - BACKGROUND: The aim of this multicentric trial was to determine the clinical
      toxicities and antitumor effects of a chemotherapy regimen of S-1 combined with
      cisplatin in patients with inoperable locally or metastatic advanced gastric
      cancer. PATIENTS AND METHODS: Forty-two patients were entered into the study. S-1
      (80 mg/m2) was administered orally daily for 14 consecutive days and 24-h
      infusion of cisplatin (70 mg/m2) was administered on day 8 of every 28-day cycle.
      RESULTS: The overall response rate was 50% and complete response rate was 5%. The
      most common adverse event was leucopenia, which occurred with grade 3 in 7
      patients (16.6%) and grade 4 in 2 patients (4.8%). Non-hematological adverse
      events were generally mild. The median survival time was 342 days. The 2-year
      survival rate was 22.9%. CONCLUSION: This combination chemotherapy is active,
      convenient and well tolerated in patients with high-grade advanced gastric
      cancer.

PMID- 15865082
TI  - Role of a CYP17 promoter polymorphism for familial prostate cancer risk in
      Germany.
AB  - BACKGROUND: A thymidine to cytosine transition (designated A2 variant) in the
      promoter region of CYP17 has previously been associated with a familial history
      of prostate cancer in North American families. The purpose of the present study
      was to determine whether this correlation could be replicated in a European
      population. MATERIALS AND METHODS: Case-control comparisons were performed by
      modelling a dominant (A1/A2 + A2/A2 vs. A1/A1) and a recessive (A2/A2 vs. A1/A2 +
      A1/A1) effect of the promoter modification. RESULTS: An insignificant
      overrepresentation of homozygous carriers of the A2 allele (recessive effect) was
      found in sporadic cases, as compared to controls. However, the A2 variant was not
      related to familial disease. CONCLUSION: Our results do not suggest a role of
      CYP17 as a high-risk susceptibility gene for familial prostate cancer, nor as a
      modifier for the disease risk in the European population.

PMID- 15865083
TI  - Sequential docetaxel followed by epirubicin-vinorelbine as first-line
      chemotherapy in advanced breast cancer.
AB  - BACKGROUND: This phase II study evaluated the efficacy and the tolerability of a
      sequential regimen of docetaxel followed by epirubicin-vinorelbine combination as
      first-line chemotherapy in advanced breast cancer. PATIENTS AND METHODS: Twenty
      seven patients received docetaxel 100 mg/m2 (4 cycles) followed by 4 cycles of
      epirubicin 90 mg/m2 (day 1) combined with vinorelbine 25 mg/m2 (days 1 and 5),
      with cycles repeated every 3 weeks. G-CSF was administered during epirubicin
      vinorelbine treatment. RESULTS: There were 1 (3.7%) CR and 14 (51.9%) PR, for an
      overall response rate of 55.6% (95% CI, 36.9%-74.3%). Median time to response,
      time to progression and overall survival were 2, 9 and 25 months, respectively.
      The dose-limiting toxicity was neutropenia (grade 3 to 4 in 85% of the patients).
      There was one toxic death due to neutropenic fever. Gastrointestinal side-effects
      were generally mild According to the Simon two-stage design the response rate was
      considered unsatisfactory and patient accrual was terminated. CONCLUSION: This
      sequential regimen appears to be moderately effective; possibly, a modulation of
      the treatment based on objective responses instead of a fixed number of cycles
      may be more appropriate in order to obtain better results.

PMID- 15865084
TI  - Ribavirin in the treatment of hepatitis C.
AB  - The hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide,
      with approximately 170-200 million people infected. The HCV virus is transmitted
      by blood and blood products and such transmission occurs primarily through drug
      use by injection, sex with an infected partner and occupational exposure. The
      severity of the disease varies widely from mild chronic hepatitis to cirrhosis
      and hepatocellular carcinoma (HCC). Nowadays, the reference treatment is
      combination therapy of pegylated interferon and ribavirin, which is an inosine
      monophosphate dehydrogenase inhibitor and immunomodulator. Efficacy of treatment
      in our clinical trials is 87% in patients infected by HCV genotypes 2 or 3,
      whereas in patients infected by HCV genotype 1 response to treatment is 66%. The
      current combination treatment has significant side-effects and sometimes is
      poorly tolerated. HCV genotypes 2 or 3 can be treated with a lower dose of
      ribavirin and a shorter course of therapy, 24 weeks vs 48 weeks for patients with
      genotype 1. There is a growing consensus that acute control of HCV infection is
      associated with a vigorous intrahepatic antiviral CD4+ and CD8+ T-cell response,
      enhanced Th1 and natural killer activity. Pretreatment genotype and response to
      therapy measured at weeks 12 and 24 of treatment have been identified as key
      determinants in decisions about continuing treatment. Elevated serum ferritin
      levels and hepatic iron deposition as well as hepatic steatosis and high ALT
      levels with chronic hepatitis C are risk factors for HCC development.
      Heterozygosityfor the C282Y mutation in HFE contributes to iron accumulation and
      fibrosis progression in chronic hepatitis C. Ribavirin could cause dose-dependent
      reversible haemolytic anaemia, which can be managed with dose reductions or with
      administration of epoetin alpha at 40,000 IU once weekly without sacrificing the
      optimal dosing of ribavarin. Among patients who received ribavirin alone, serum
      ALT levels and necroinflammatory features of liver histology were improved,
      whereas symptoms, HCV RNA levels and hepatic fibrosis scores were not changed
      significantly from baseline. For HCV-HIV co-infected patients, treatment is given
      when blood CD4 counts are above 350/ml and before antiretroviral (ART) treatment
      is needed.

PMID- 15865085
TI  - Neutron therapy, prognostic factors and dedifferentiation of adenoid cystic
      carcinomas (ACC) of salivary glands.
AB  - PURPOSE: Analysis of the efficacy of fast neutron radiotherapy in the treatment
      of adenoid cystic carcinomas (ACC) of the salivary glands, identification of
      prognostic variables and dedifferentiation after radiotherapy. PATIENTS AND
      METHODS: Histological slides of primary and recurrent lesions of 71 patients were
      reviewed to confirm the diagnosis and to analyse subtypes. Median follow-up was
      52 months. Local control rate and overall survival were analysed in multivariate
      analysis. Complications are also described. RESULTS: Primary vs. recurrent
      therapy (p=0.001), margin-status (p=0.01) and subtype (p=0.019) influenced
      overall survival. Primary vs. recurrent therapy (p=0.001), margin-status
      (p=0.018) and T-stage (p=0.043) influenced local control rate. Dedifferentiation
      was seen in only 1/17 cases. CONCLUSION: The calculated prognostic factors
      illustrate the importance of a radical primary therapy. Histological subtype is a
      significant additional factor for overall survival and, in case of
      dedifferentiation, it is a strong predictor of a detrimental outcome.

PMID- 15865086
TI  - Clinical significance of serum CEA protein and CEA mRNA after resection of
      colorectal liver metastases.
AB  - BACKGROUND: It is difficult to predict the recurrence of colorectal liver
      metastasis after curative hepatectomy. We investigated the relationship between
      subsequent metastasis and both CEA protein and CEA mRNA (TaqMan PCR) diachronic
      levels. PATIENTS AND METHODS: The subjects were 30 patients with colorectal liver
      metastases. Serum CEA protein and CEA mRNA assays were performed every month
      after hepatectomy. RESULTS: Metastasis recurred in 21 of the 30 patients. The CEA
      mRNA assay showed 26 cases with high (H) levels and 4 with low (L). Among the 15
      patients whose protein levels were not elevated (NE group), 6 had recurrence; all
      6 belonged to the mRNA H group. None of the 4 patients in the mRNA L group had
      recurrence. In the protein-elevated (E) group (DFI > 6 months) (n = 7), mRNA was
      elevated in 5 cases (71.4%) 6 months before recurrence, whereas protein was
      elevated in 1 case. The sensitivity, specificity and accuracy of CEA protein/mRNA
      for identifying recurrence were 71.4/100, 100/44.4, and 80/83.3%, respectively.
      CONCLUSION: CEA mRNA is more sensitive than CEA protein in detecting recurrence.
      CEA mRNA may be useful for identifying high-risk groups or detecting recurrence
      at an early stage, when the CEA protein level is still low.

PMID- 15865087
TI  - Phase II trial of carboplatin, paclitaxel plus vinorelbine in non-small cell lung
      cancer patients.
AB  - BACKGROUND: Vinorelbine was added to carboplatin plus paclitaxel to determine
      efficacy and toxicity in non-small cell lung cancer (NSCLC) patients with good
      performance status. PATIENTS AND METHODS: Vinorelbine 30 mg/m2 plus paclitaxel
      175 mg/m2 plus carboplatin AUC 5 was administered every three weeks for a maximum
      of 6 cycles. RESULTS: One out of 37 patients had a complete and 12 a partial
      remission (35% response rate). Six patients (16%) had disease stabilization and
      18 (49%) progressed. Grade III or IV neutropenia occurred in 11 (30%) and febrile
      neutropenia in 6 (16%) patients. Grade III/IV neuropathy was observed in 6 (16%)
      patients. The median time to progression was 6 months (95% CI 4.0 - 8.0), and
      median survival 11 months (95% CI 8.3 - 13.7). One- and two-year survival was 41%
      (95% CI 24 - 58) and 24% (95% CI 8.7 - 39.1), respectively. CONCLUSION: This
      triple-chemotherapy combination is feasible. The response rates justify further
      investigation in similar patient subgroups.

PMID- 15865088
TI  - Histological vascular invasion by tumors is a risk factor for distant metastasis
      in malignant fibrous histiocytoma.
AB  - BACKGROUND: The appearance of distant metastasis is a fatal sign in patients with
      soft tissue sarcoma. Therefore, we studied the risk factors associated with
      distant metastasis that appear in malignant fibrous histiocytoma. MATERIALS AND
      METHODS: The study group comprised sixty patients treated for malignant fibrous
      histiocytoma at our hospital between 1991 and 2002. We retrospectively studied
      whether age, tumor size, tumor site, developmental form, surgical margin, local
      recurrence, histological subtype, vascular invasion and histological grade are
      risk factors associated with the appearance of distant metastasis. RESULTS: A
      univariate analysis showed that, for those patients older than 70 years of age,
      insufficient surgical margin, the presence of local recurrence and vascular
      invasion are significant risk factors associated with the appearance of distant
      metastasis. A multivariate analysis showed only the presence of vascular invasion
      to be a significant risk factor as well. CONCLUSION: Histological vascular
      invasion by tumors is a risk factor associated with distant metastasis that
      appears in malignant fibrous histiocytoma. Taking early measures for patients
      with vascular invasion is necessary to improve the prognosis.

PMID- 15865089
TI  - Primary chemotherapy with epirubicin and vinorelbine in women with locally
      advanced breast cancer.
AB  - BACKGROUND: To assess the activity and toxicity of primary chemotherapy with
      epirubicin (60 mg/m2 every other week) and vinorelbine (25 mg/m2, weekly) plus
      granulocyte colony-stimulating factor (G-CSF) for 12 weeks, in patients with
      locally advanced breast cancer in a multicenter setting. PATIENTS AND METHODS:
      Patients with stage IIIA or IIIB breast cancer, not older than 70, were eligible.
      A two-stage phase II design was applied. Response was assessed clinically,
      instrumentally and pathologically. RESULTS: Out of 48 enrolled patients, 87.5%
      received all planned cycles, with a median dose-intensity of 30 mg/m2/week for
      epirubicin and 23.8 mg/m2/week for vinorelbine. A clinical or instrumental
      objective response was reached in 42 patients (87.5%, exact 95% CI: 74.7-95.3);
      significant downstaging was reached in all but one patient; 6 cases had a
      pathological complete response in the breast, and 2 cases in the lymph nodes too
      (pathological complete response rate 4.2%, exact 95% CI: 0.5-14.2); a further 2
      patients had only microscopic cancer foci at pathological examination of the
      breast. Radiological tests underestimated the treatment effect on the breast.
      Toxicity was mild, neutropenia being the most frequent (grade 3-4 in 47% of
      patients), but never complicated with fever or sepsis. Mild constipation (< or
      =grade 2) occurred in 35% of patients. Moderate to severe asthenia occurred in
      12% of 6 patients. No cardiac toxicity was reported. At 3 years, disease-free
      survival was 68% and overall survival 81%. CONCLUSION: Primary chemotherapy with
      epirubicin every other week, weekly vinorelbine and G-CSF support is highly
      active and well tolerated in patients with locally advanced breast cancer.

PMID- 15865090
TI  - Feasibility of sentinel node concept in gastric carcinoma: clinicopathological
      analysis of gastric cancer with solitary lymph node metastases.
AB  - BACKGROUND: The feasibility and diagnostic reliability of sentinel lymph node
      biopsy of gastric carcinoma are still unclear and controversial. PATIENTS AND
      METHODS: To assess the applicability of the sentinel node concept to gastric
      carcinoma, we retrospectively analyzed the location of metastatic lymph nodes in
      patients with only one or two lymph node metastases. RESULTS: A total of 135
      patients, who underwent gastrectomy with D2 lymphadenectomy for primary gastric
      adenocarcinoma between 1997 and 2001, were enrolled in this study. An average of
      39 lymph nodes were resected and analyzed for each patient. Of the 135 patients,
      88 (65%) were subtyped as pN+ (with lymph node metastasis); of the latter, 15
      cases (pT1-3; 17% of N+ cases) showed one or two lymph node metastases. In 14
      (93%) of these patients, lymph nodes directly adjacent to the primary tumor were
      involved. Skip metastases were only seen in one patient with cardia carcinoma and
      lymph node involvement of compartment II (left gastric artery). CONCLUSION: In
      patients with gastric carcinoma, especially in early stage carcinoma, the
      phenomenon of skip metastasis is infrequent. Therefore, the sentinel node concept
      may be feasible in gastric cancer.

PMID- 15865091
TI  - Serrated and microtubular colorectal adenomas in Italian patients. A 5-year
      survey.
AB  - Colorectal adenomas from 1552 Italian patients were histologically classified
      into tubular (TAs), tubulo-villous (TVAs), villous (VAs), serrated (SAs) and
      microtubular (MTAs). The purpose was to compare the results to those in 3135
      colorectal adenomas from Swedish patients. Of the 1552 adenomas, 827 (53%) were
      TAs, 352 (23%) TVAs, 196 (12%) VAs, 102 (7%), SAs and 14 (0.9%) MTAs. The
      remaining 61 (4%) were of combined phenotypes (COMBAs). The percentage of VA
      (considered as the most important dysplastic precursor of colorectal cancer) was
      higher in Florence than in Stockholm. Notably, the incidence of colorectal cancer
      in males was also higher in Florence (78.6/10(5)) than in Stockholm (57.2/10(5)).
      Notwithstanding, the highest rate of submucosal invasion (7%) was found among
      SAs. The diameter of the largest section was used to define the size of the
      largest adenoma in individual patients. Of the 1380 neoplasias measuring < or =12
      mm, only 0.9% (n=13) had invasive carcinomas, but as many as 8.1% (n=14) of the
      172 neoplasias measuring > or =13 mm. SAs and MTAs are special adenoma phenotypes
      with particular morphological and cell proliferative attributes at variance from
      those of TAs, VAs or TVAs. In the light of the present results, it is proposed
      that SAs and MTAs are included in future reports of colorectal adenomas in order
      to compare their frequency worldwide.

PMID- 15865092
TI  - Expression of retinoblastoma and p53 pathway-related proteins in resectable
      invasive ductal carcinoma of the pancreas: potential cooperative effects on
      clinical outcome.
AB  - BACKGROUND: The retinoblastoma protein (RB) is an important cell cycle regulator.
      RB also plays an important role in the regulation of apoptosis, which is mediated
      by interaction of p53 signaling mediators. The present study was designed to
      assess the clinicopathological significance of RB and p53 pathway-related
      proteins (p53, p21WAF1/CIP1 and Bax) expression in resectable invasive ductal
      carcinoma (IDC) of the pancreas. MATERIALS AND METHODS: The present study
      included 79 pancreatic IDC patients, who received surgery between 1982 and 2002.
      The expression of RB and p53 pathway-related proteins (p53, p21WAF1/CIP1 and Bax)
      were analyzed by immunohistochemistry. RESULTS: RB was expressed in 45 (57%) of
      the 79 patients. RB expression correlated significantly with histological grade
      and grade of nodal involvement. The positive rate of p53, p21WAF1/CIP1 and Bax
      expression was 49%, 48% and 67%, respectively. RB expression alone did not have a
      significant effect on patient survival. However, coexpression analysis of RB and
      p53 pathway-related proteins indicated that, in the patients with RB (+) IDC, the
      p21WAF1/CIP1 (+) group had a significantly higher survival rate than the
      p21WAF1/CIP1 (-) group. On the other hand, in the patients with RB (-) IDC, the
      Bax (+) group had a significantly higher survival rate than the Bax (-) group.
      Multivariate analysis indicated that, in the RB (-) group, pTNM stage, adjuvant
      chemotherapy and Bax expression were significant variables. CONCLUSION: The
      evaluation of RB expression combined with the mediators of the p53 pathway,
      p21WAF1/CIP1 and Bax, may provide more accurate information regarding clinical
      outcome, beyond that which is provided by RB expression alone.

PMID- 15865093
TI  - Clinical impact of metastatic lymph node ratio in advanced gastric cancer.
AB  - BACKGROUND: We examined the prognostic value of metastatic lymph node ratio (the
      ratio of the number of metastatic lymph nodes to the number of lymph nodes
      removed) after curative resection. PATIENTS AND METHODS: The results of surgery
      on 758 patients were assessed by uni-and multi-variate analysis by classifying
      the metastatic lymph node ratio into 4 categories: 0, <0.1, >0.1 <0.2, >0.2.
      Furthermore, the rationality and prognostic significance of the lymph node ratio
      classification as a nodal staging system was compared with the UICC/TNM
      classification. RESULTS: Univariate analysis showed that operative method,
      location of tumor, macroscopic appearance, tumor diameter, depth of invasion,
      metastatic lymph node ratio, lymphatic invasion and venous invasion significantly
      affected prognosis. A Cox proportional regression hazard model revealed that
      macroscopic appearance, tumor diameter, depth of invasion and metastatic lymph
      node ratio independently influenced prognosis. Among patients with pN2 by the
      UICC/TNM classification, survival in those with a metastatic lymph node ratio
      less than 0.1 was significantly better than in those with a higher metastatic
      lymph node ratio. CONCLUSIONS: The metastatic lymph node ratio is an independent
      prognostic factor. Extended lymphadenectomy could increase survival of patients
      with pN2 gastric cancer by decreasing the metastatic lymph node ratio below 0.1.

PMID- 15865094
TI  - Preoperative CEA and PPD values as prognostic factors for immunochemotherapy
      using PSK and 5-FU.
AB  - PURPOSE: Immunochemotherapy using PSK used as postoperative adjuvant chemotherapy
      for colorectal cancer in Japan, is a treatment that depends on the
      immunocompetence of the host. Therefore, we analyzed the data of Hokuriku
      district conducted by the CIP study group to compare the long-term survival for
      preoperative CEA level and PPD reaction. PATIENTS AND METHODS: Between February
      1991 and March 1993, 87 patients with primary colon cancer and macroscopic lymph
      node metastasis (macroscopic Dukes' C) underwent macroscopic curative resection.
      The patients were randomly allocated to receive 5-FU/PSK therapy or 5-FU alone.
      The 7-year disease-free survival (DFS), 7-year overall survival (OS) and 7-year
      cancer death survival (CDS) were compared using the preoperative CEA levels and
      PPD values. RESULTS: In cases with preoperative CEA level > or =3.0 ng/mL, the 7
      year DFS, 7-year OS and 7-year CDS were significantly better in the PSK group
      (85.7, 90.5, 90.5%) than in the control group (52.4, 52.4, 57 1%; p=0.019, 0.007,
      0.014,). In cases with preoperative PPD level <19.0 mm, the 7-year DFS, 7-year OS
      and 7-year CDS were significantly better in the PSK group (85.7, 85.7, 89.3%)
      than in the control group (56.7, 60.0, 63.3%; p=0.018, 0.036, 0.028). Recurrence
      was significantly less in the PSK group. The DFS tended to be superior in the PSK
      group (87.4%) compared to the control group (69.9%) for hematogenous metastasis.
      CONCLUSION: The present study demonstrated that preoperative CEA and PPD, that
      can be measured easily in the clinical setting, may be effective indicators of
      postoperative adjuvant immunochemotherapy using PSK.

PMID- 15865095
TI  - Carcinogenesis: a cellular model for age-dependence.
AB  - BACKGROUND: Certain characteristics of cancer remain invariant between
      populations, the age of peak risk, the age ranges of significant and
      insignificant risk, and the pattern of risk variation with age. We offer an
      explanation that is built by analogy on that for trisomy 21. MATERIALS AND
      METHODS: We calculated the rate of change in risk with age for the most common
      cancers, death from all causes, trisomy 21/birth, and trisomy 21/1000 women.
      RESULTS: Beyond some milestone age, the risk of death from all causes and trisomy
      21/birth exhibit constant acceleration, while risk of cancer and trisomy 21/1000
      women exhibit increasing deceleration. CONCLUSION: With advancing age, the risk
      of abnormal cell division increases continuously but remains harmless until some
      tissue-specific milestone, e.g., depletion of stem cells, and is then damped by a
      continuous decline in rate of cell division.

PMID- 15865096
TI  - Phase II trial of irinotecan and raltitrexed in chemotherapy-naive advanced
      colorectal cancer.
AB  - BACKGROUND: Irinotecan and raltitrexed are active agents in advanced colorectal
      cancer (ACC) and preclinical data suggest a remarkable synergistic activity.
      Phase I studies demonstrated that single-agent full dose of both drugs can be
      administered with moderate toxicity. The aim of this phase II trial was to assess
      the activity and tolerability of the combination in untreated ACC. PATIENTS AND
      METHODS: Forty-eight patients entered the trial and received irinotecan 350 mg/m2
      d.1 and raltitrexed 3 mg/m2 d.2, every three weeks. After recruitment of the
      first 16 patients, grade III-IV toxicity was observed in 6 patients (38%).
      Therefore, an amendment reduced by 15% the dose of both drugs (irinotecan 300
      mg/m2, raltitrexed 2.6 mg/m2). RESULTS: A total of 290 cycles were administered
      (range 1-18, median number 6). According to intention-to-treat analysis, the
      overall response rate was 27% (95% confidence interval 16%-42%), including 3
      complete responses and 10 partial responses. The median duration of response was
      10 months, while median progression-free survival and overall survival were 5 and
      14 months, respectively. In the first 16 patients, the main toxicities were grade
      III-IV diarrhea in 25% and grade III-IV neutropenia in 13%. In the subsequent 32
      patients, they were grade III-IV diarrhea in 34% and grade III neutropenia in 6%.
      Two toxic deaths occurred. CONCLUSION: The combination irinotecan-raltitrexed is
      an active regimen, but the significant incidence of side-effects requires
      accurate patient selection and, eventually, new schedules.

PMID- 15865097
TI  - Significance of RNA reference in tumour-related gene expression analyses by cDNA
      array.
AB  - The cDNA array technique is an efficient approach for studying the expression of
      a large number of genes in a single experiment. The cDNA array analysis indicates
      the relative level of corresponding gene expression from a specimen and a
      reference. Our investigation was performed to address the significance of
      reference RNA on the outcome of the cancer-related gene expression profile
      obtained from cDNA array analysis. Human head and neck squamous cell carcinoma
      (HNSCC) biopsies and 5 sources of RNA reference were used for this purpose. In
      these biopsies, each individual patient expressed a unique set of genes both in
      normal and tumour tissue. It is important to note that 5 striking patterns of
      tumour-related gene expression were obtained according to the 5 references used.
      Significant differences in 60%, 16%, 15% and 15% of the genes expressed were
      shown when autologous normal matched tissue biopsy references were compared to
      pooled cell lines, allogenic normal mixed cell types, tumours or allogenic normal
      matched cell type references, respectively. Thus, theoretically and our study
      suggested that patient autologous normal cells matching with the tumour type
      should be the most suitable reference in cDNA array for the identification of
      individual tumour gene profiles with clinical purpose.

PMID- 15865098
TI  - Intravascular papillary endothelial hyperplasia (Masson's hemangioma) presenting
      as a soft-tissue sarcoma.
AB  - Intravascular papillary endothelial hyperplasia (Masson's hemangioma) is an
      unusual benign, non-neoplastic, vascular lesion characterized histologically by
      papillary fronds lined by proliferating endothelium. It may appear as a primary
      or pure form developing in a distended vessel, or it can be associated with
      hemangiomas, pyogenic granulomas, or lymphagiomas. Nearly all lesions are
      intimately associated with a thrombus in various stages of organization. The main
      significance of intravascular papillary endothelial hyperplasia is its clinical
      and histological resemblance to soft-tissue sarcoma and possible
      misinterpretation as such. A case of intravascular papillary endothelial
      hyperplasia clinically diagnosed and treated as a low-grade angiosarcoma, in a 60
      year-old man, presenting with a mass in the left thigh, is reported.

PMID- 15865099
TI  - The apoptotic response of liver and colorectal liver metastases to focal
      hyperthermic injury.
AB  - BACKGROUND: Ablation of liver tumours by focal hyperthermia causes tissue injury
      not only by direct effects, but also by progressive tissue damage following the
      initial heat application. The mechanism by which this progressive injury occurs
      remains undefined. Stimulation of apoptosis following the initial heat stimulus
      may be involved in this progression. The role of apoptosis in the subsequent
      progression of focal hyperthermia injury was investigated in liver and colorectal
      liver metastases in a murine model. MATERIALS AND METHODS: Focal hyperthermia
      produced by laser (Nd-YAG--wavelength 1064 nm) was applied to the liver and
      colorectal liver metastases in CBA mice (2 Watts for 50 seconds). The animals
      were killed at 0, 12, 24, 48, 72, 120 and 168 hours after the application of
      focal hyperthermia. Haematoxylin and eosin staining and immunohistochemistry were
      performed on paraffin sections to assess the extent of tissue necrosis. Apoptosis
      was examined by assessment of DNA fragmentation using terminal deoxynucleotidyl
      transferase d-uridine triphosphate nick end labelling (TUNEL) and activated
      Caspase 3 immunostaining. The sequence of the apoptotic response was determined
      at the treated tissue margins and compared to untreated liver and tumour.
      RESULTS: Focal hyperthermia produced progressive tissue injury in both liver and
      colorectal liver metastases. TUNEL labelling was less specific than activated
      Caspase 3 in detecting apoptotic cells. Apoptosis was detected and peaked at 12
      hours following therapy based on activated Caspase 3 staining, before returning
      to baseline at 72 hours. In tumour tissue, the apoptotic response was more
      sustained, peaking at 24 hours before returning to baseline levels by 96 hours
      following therapy. CONCLUSION: Increased apoptosis occurs following the
      application of focal hyperthermia to normal liver and colorectal metastases. The
      apoptotic response is more sustained in tumour tissue and contributes to the
      progressive injury that is evident after the initial heat stimulus.

PMID- 15865100
TI  - Prevalence and risk of cancer of focal thyroid incidentaloma identified by 18F
      fluorodeoxyglucose positron emission tomography for cancer screening in healthy
      subjects.
AB  - The aim of this study was to define the clinical prevalence and rate of
      malignancy of focal thyroid incidentaloma in a relatively large number of
      individuals with application of 18F-fluorodeoxyglucose (FDG) Positron Emission
      Tomography (PET) in asymptomatic individuals. The subjects consisted of 4803
      physical check-up examinees (2638 men, 2165 women; mean age+/-SD, 52.8+/-9 years
      old) with non-specific medical history. Whole-body FDG PET was performed on all
      patients. Focal hypermetabolic areas of thyroid, with an intensity equal to or
      exceeding the level of FDG uptake in the liver, were considered abnormal and
      interpreted as thyroid incidentaloma. Among the 4803 FDG PET examinations,
      thyroid incidentaloma was present in 60 examinations, among which, 50 had further
      examination with ultrasound-guided fine-needle aspiration (FNA), revealing 43
      benign lesions and 7 papillary carcinomas. Of 7 examinees diagnosed with cancer,
      2 had lymph nodes metastasis. The mean and standard deviation of standard uptake
      value (SUV) in benign and carcinoma was 2.6+/-1.01 and 6.7+/-3.66, respectively.
      Thyroid incidentaloma identified by FDG-PET occurred with a frequency of 1.2%
      (60/4803). Of the thyroid incidentalomas that underwent FNA and surgery, 14%
      (7/50) were found to be malignant. It is possible to differentiate benign from
      carcinoma of thyroid incidentalomas by the increased rate of glycolysis (SUV) in
      the carcinoma. The small size and moderate FDG uptake of thyroid incidentalomas
      per se cannot guarantee low risk in incidentally found thyroid cancers.

PMID- 15865101
TI  - Triplet chemotherapy with docetaxel, gemcitabine and liposomal doxorubicin,
      supported with subcutaneous amifostine and hemopoietic growth factors, in
      advanced non-small cell lung cancer.
AB  - The activity of a triplet of chemotherapeutic drugs, namely docetaxel,
      gemcitabine and liposomal doxorubicin, was investigated in patients with advanced
      non-small cell lung cancer. The regimen was supported with amifostine
      cytoprotection (1000mg injected subcutaneously) and hemopoietic growth factors
      (rhuG-CSF and rhuEPO) in an attempt to minimize the substantial toxicity reported
      in previous studies investigating docetaxel/gemcitabine chemotherapy. Twenty
      chemotherapy- naive patients with advanced non-small cell lung cancer (NSCLC) (18
      with stage IV and 2 with stage IIIb) were recruited. None of the patients
      presented with grade 3-4 hematological or non-hematological toxicity. Palmar
      plantar erythrodysesthesia grade 2 was noted in 6/20 (30%),
      mucositisloesophagitis grade 2 in 3/20 (15%) and mild alopecia in 6/20 (30%)
      patients. No case of interstitial pneumonia was noted. The overall response rate
      (complete and partial) in 18 evaluable patients was 33% (6/18), with 1/18 (5%)
      patients achieving complete response. The median survival was 11 months. The
      efficacy of the regimen was as high as the one reported in gemcitabine/docetaxel
      studies, but the toxicity was remarkably lower. Amifostine may have contributed
      to the better tolerance profile observed.

PMID- 15865103
TI  - Temozolomide and cisplatin in avdanced malignant melanoma.
AB  - BACKGROUND: Temozolomide (TMZ) is an oral alkylating agent; it produces DNA
      methyl adducts, which are removed by the DNA repair enzyme AGAT. In vitro studies
      suggest that CDDP may enhance the antitumor activity of TMZ due to the ability of
      cisplatin (CDDP) to down-regulate AGAT activity. In a previous phase I study, the
      combination of TMZ and CDDP was tested, and the recommended dose for each drug
      was defined. On the basis of these results, we designed a phase II study to
      evaluate the activity and safety profile of the TMZ-CDDP association in patients
      with advanced melanoma. PATIENTS AND METHODS: From March 2001 to March 2002, 37
      patients with metastatic melanoma, not amenable to surgery, were enrolled in this
      study. All eligible patients were treated with the combination of CDDP 75 mg/m2
      i.v. d 1, TMZ 200 mg/m2 p.o. days 1-5 recycled every 4 weeks. Interferon alpha2b
      (IFN alpha2b) was administered at the end of chemotherapy to responsive patients
      at the dose of 5 M.I. U s.c. 3 times a week for 1 year. RESULTS: A total of 174
      courses were administered, with a median number of 4 courses/patient (range 1
      10). After chemotherapy, 9 CRs and 9 PRs were observed for an overall response
      rate of 48.6% (95% C.I., 31.9%-65.6%). One of 5 patients with initial brain
      metastases showed a complete response to the therapy. Five out of 9 CR patients
      were still with no evidence of recurrence, ranging from 28+ to 82+ weeks. The
      median survival time was 48 weeks. The schedule was well tolerated, with the most
      frequent adverse events reported being nausea and vomiting (59%), alopecia (14%)
      and fatigue (11%), all well controlled by supportive therapy. Haemotological
      toxicities were mild to moderate. Side-effects attributable to IFN alpha2b were
      also mild and manageable. CONCLUSION: The combination of TMZ and CDDP seems to be
      active in untreated patients with advanced melanoma. Absence of recurrence in the
      majority (5/9; 56%) of CR patients seems to indicate that IFN may act on the
      duration of the response to chemotherapy. The schedule was well tolerated, with
      nausea and vomiting as the most frequent adverse events.

PMID- 15865104
TI  - Search for meaningful support and the meaning of illness in German cancer
      patients.
AB  - BACKGROUND: Spiritual needs are an essential component of holistic health care.
      Several studies have shown that religious involvement and spirituality are
      associated with better health outcome, coping skills and health-related quality
      of life. PATIENTS AND METHODS: Using the newly developed SpREUK inventory, we
      examined how German cancer patients (n=115) by themselves view the impact of
      spirituality and religiosity (SpR) on their health and how they cope with
      illness. RESULTS: Cancer patients with both a religious and spiritual attitude
      had significantly higher values in the search for meaningful support and in
      addressing the stabilizing effects of SpR than patients without such attitudes.
      Patients with non-spiritual religious attitudes had a lower perception of the
      beneficial effects of their SpR and significantly lower needs for meaningful
      support. Female cancer patients were convinced that finding access to a spiritual
      source has a positive influence on their illness, that illness has meaning,
      regard illness as a chance for their own development and as a hint to change
      life. CONCLUSION: Knowledge of a patient's spirituality can help service
      providers predict aspects of psychosocial needs and to respond sensitively and
      appropriately. The SpREUK questionnaire is a useful tool to define patients who
      are more in need of spiritual support than others.

PMID- 15865102
TI  - Tissue expression and serum levels of the oncoprotein HER-2/neu in 157 primary
      breast tumours.
AB  - BACKGROUND: We studied HER-2 expression in paired serum and tissue samples, in
      157 selected cases from 701 consecutive primary breast cancer patients with pre
      treatment HER-2 extracellular domain (ECD) > or = 10 ng/ml, or < 10 ng/ml but
      showing a HER-2 ECD lead time before first metastasis. PATIENTS AND METHODS: HER
      2 ECD was measured by the Immuno 1 automated ELISA (Bayer). Tumour tissue was
      analysed by immunohistochemistry (IHC) with Dako A 0485 and CB 11 antibodies and
      scored with the Dako scoring system. RESULTS: Mean HER-2 ECD was 12.48+/-7.08
      ng/ml and 21/157 (13.4%) sera were > or = 15 ng/ml (cut-off). Forty tumours
      (25.48%) showed both invasive and intraductal components, 3 (1.91%) were pure in
      situ carcinomas and 114 (72.61%) were pure invasive tumours. Elevated HER-2 ECD
      concentration was related only to pT (p=0.0008), histological grade (p=0.0465),
      presence of comedonecrosis (p=0.0123) or comedo-type carcinoma (p=0.041) and was
      unrelated to the presence of an intraductal component. HER-2 ECD was > or = 15
      ng/ml in 48% of Dako 3+ and 60% of CB 11 2+ and 3+ tumours. By logistic
      regression analysis, the significant parameters associated with HER-2 ECD
      concentration were pT (p=0.0038) and Dako 3+ scores (p=0.0005). In Dako 3+ or CB
      11 2+3+ tumours, elevated mean HER-2 ECD concentrations were observed only when
      pT exceeded 28-30 mm (p=0.0062 and p=0.0036, respectively). CONCLUSION: In breast
      tumours, a threshold in size and HER-2 overexpression is necessary to observe
      elevated concentrations of HER-2 ECD at diagnosis. This information may be useful
      when the primary tumour is not available for IHC.

PMID- 15865105
TI  - Clinical value of bone remodelling markers in patients with bone metastases
      treated with zoledronic acid.
AB  - BACKGROUND: Bisphosphonates have an established role in the treatment of bone
      metastases from a variety of solid tumours. The objective response to anti
      resorptive treatment cannot be evaluated by imaging techniques. A number of bone
      remodelling markers have been associated with bone metastases status; among them,
      urine and serum levels of N-terminal telopeptide of collagen type I (NTx) seem to
      have the best diagnostic accuracy. However, serum NTx has not yet been properly
      evaluated. PATIENTS AND METHODS: Seventy-one consecutive patients with newly
      diagnosed skeletal metastases were enrolled in this prospective study. All of
      them were treated with zoledronic acid at 4 mg, every 3 or 4 weeks. Serum NTx and
      bone-isoform of alkaline phosphatase (BAP) were measured by enzyme-linked
      immunosorbent assays at baseline and every 2 months thereafter. RESULTS: At
      baseline, serum NTx and BAP levels were significantly higher in patients with
      blastic than lytic bone lesions and in those with multiple rather than few bone
      site involvement. Forty-seven patients were followed for a median period of 139
      days. Zoledronic acid resulted in a significant NTx reduction at first and second
      post-treatment evaluations (mean reduction of 43% at first evaluation);
      thereafter, mean NTx levels remained suppressed. In contrast, BAP levels did not
      show any significant changes. Bone disease progression resulted in a significant
      NTx elevation by an average of 69%. The initial response of NTx to zoledronic
      acid was correlated with the long-term clinical outcome of bone disease: patients
      with an initial NTx elevation had a significantly higher rate of bone disease
      progression compared to those with an initial NTx decline (66.7% versus 18.8%,
      p=0.001). Extraskeletal disease or bone irradiation did not influence NTx
      response. CONCLUSION: Serum NTx appears to be a useful marker in monitoring
      patients with skeletal metastases, as it is correlated with the type and bulk of
      bone disease and reflects bone disease progression. It is also useful in
      monitoring bisphosphonate therapy, while the initial response to this therapy
      seems to bear a prognostic significance for bone disease outcome.

PMID- 15865107
TI  - Solitary parenchymal splenic recurrence of ovarian adenocarcinoma: a case report
      and review of the literature.
AB  - We report a rare case of solitary parenchymal splenic recurrence of epithelial
      ovarian cancer which developed 27 months after the initial treatment. The
      patient, a 53-year-old woman, with a history of breast cancer, underwent total
      abdominal hysterectomy bilateral salpingo-ophorectomy (TAH & BSO), omentectomy
      and pelvic lymph node sampling for a serous carcinoma of the ovaries (stage
      IIIB). She subsequently received 6 cycles of cisplatinum chemotherapy. During
      follow-up, rising CA 125 serum levels heralded the 6 x 6 cm parenchymal splenic
      lesion which was documented by CT scan. She underwent splenectomy after
      pneumococcal vaccination, sandostatin and chemoprophylaxis. Histopathological
      evaluation revealed metastatic parenchymal disease consistent with recurrent
      ovarian cancer. She remains alive and disease-free for 20 months since the last
      operation. Isolated parenchymal splenic lesions are very rare and may occur as a
      late recurrence in epithelial ovarian cancer. Splenectomy can be performed with
      acceptable morbidity and confers a substantial survival benefit to patients.

PMID- 15865106
TI  - No association between genetic polymorphisms in NAD(P)H oxidase p22phox and
      paraoxonase 1 and colorectal cancer risk.
AB  - BACKGROUND: Impaired metabolism of ingested toxic or carcinogenic compounds is a
      postulated mechanism underlying colorectal cancer (CRC). Furthermore, it is
      suggested that reactive oxygen species (ROS) may play a role in human cancer
      development. Polymorphic variations in NAD(P)H oxidase p22phox and paraoxonase 1
      (PON1) enzyme activities may alter superoxide production or the rate of chemical
      metabolism, respectively, and this may influence the risk for CRC. Therefore,
      this study was designed to determine whether the distribution of polymorphisms in
      NAD(P)H oxidase p22phox and PON1 genes was different in sporadic CRCpatients
      versus healthy controls. MATERIALS AND METHODS: The study participants (365 cases
      and 354 controls) were all of Caucasian origin. NAD(P)H oxidase p22phox H72Y, and
      PON1 L55M and Q192R polymorphisms were genotyped by polymerase chain reaction,
      eventually followed by restriction-fragment-length-polymorphism analyses.
      RESULTS: Comparison of CRC patients and controls revealed no significant
      differences in genotype distributions or allele frequencies for polymorphisms in
      the NAD(P)H oxidase p22phox and PON1 genes. Investigation of potential
      associations between the variant NAD(P)H oxidase p22phox or PON1 alleles and the
      clinical characteristics, tumour location or tumour stage, also did not reveal
      statistically significant associations. CONCLUSION: Variant genotypes of NAD(P)H
      oxidase p22phox and PON1 do not contribute to the susceptibility to CRC.

PMID- 15865108
TI  - Surgery in the air--evacuating Finnish tsunami victims from Thailand.
AB  - In connection with the Asian tsunami disaster on December 26, 2004, a specially
      equipped Finnair B-757 airplane capable of evacuating badly injured patients was
      remodeled into an ambulance airplane. The vehicle could take up to 22 severely
      injured or ill patients and intensive care and limited surgical procedures could
      be provided to the patients. The plane was manned with a civilian medical team of
      37 physicians and nurses. The plane left for Thailand to evacuate the most
      severely injured Finnish citizens within 10 hours of the evacuation decision. A
      total of 14 patients including 4 critically ill (two on ventilator) were
      transferred to Helsinki within 32 hours of takeoff. The medical team included a
      general, an orthopedic and a plastic surgeon. Soft tissue wounds, some of them
      severely infected, were the most common injuries, followed by extremity fractures
      and head injuries. The surgical procedures that were performed mid-air included
      wound surgery, to remove necrotic tissue, and external fixation and fasciotomy
      for a lower extremity fracture. The facilities under these circumstances would
      allow performing life-saving procedures to maintain airway and breathing, and
      surgical procedures of the soft tissues, extremity and pelvic fractures. Cavitary
      surgery would require additional equipment and resources.

PMID- 15865109
TI  - Early definitive closure of the open abdomen: a quiet revolution.
AB  - Contrary to the management strategy recommended only 2-3 years ago, temporarily
      covering the open abdomen with an absorbable mesh or a plastic sheath without
      preserving the peritoneal space is no longer considered in the patient's best
      interest. The use of the vacuum pack, in conjunction with vacuum-assisted wound
      management and new biological prostheses now offer patients with an open abdomen
      a better and simpler alternative to the giant "planned ventral hernia". With very
      few exceptions in the most critically ill patients, the survivors of damage
      control surgery or infected pancreatic necrosis should not be sent home with a
      huge defect only to undergo a complex reconstruction a year later. Simpler and
      better alternatives exist. The new concepts and technologies presented in this
      review, when widely adopted, will rapidly translate into safer and better
      management of the patient with an open abdomen.

PMID- 15865110
TI  - Preoperative assessment of small tumours in women with breast cancer.
AB  - BACKGROUND AND OBJECTIVES: In patients with breast cancer, planning of the
      surgical strategy may rely on preoperative tumour size. The optimal method for
      assessment of small tumours has not been established. We compared findings from
      preoperative mammography and ultrasonography with histopathological tumour size
      in patients treated with breast-conserving surgery. MATERIAL AND METHODS: The
      study was retrospective and the setting a single institution clinic with free
      referral of patients. The patients were examined before the operation with
      mammography, ultrasonography, and findings were compared with postoperative
      histopathological tumour size. RESULTS: The study included 131 patients (median
      age was 59) years with grade I, II, and III cancers in 47, 71 and in 13 patients,
      respectively. The medium histological tumour size was 14 mm, range 4-45 mm. A
      wide 95% confidence interval between histopathological tumour size and
      preoperative mammography (standard deviation 4.8 mm) and ultrasonography
      (standard deviation 4.8 mm) was found. The combination of mammography and
      ultrasonography did not improve the results (standard deviation 4.3 mm).
      Preoperative mammography tended to over estimate the tumour size compared with
      histological tumour size whereas preoperative ultrasonography tended to
      underestimate the tumour size. CONCLUSION: In this retrospective study with
      preoperative evaluation of small breast cancers by mammography and
      ultrasonography, wide 95% confidence intervals for the methods were found and
      they should therefore be used with caution in the planning of the surgical
      strategy.

PMID- 15865111
TI  - Recurrences after immediate reconstruction in breast cancer.
AB  - AIM: To determine the incidence of and reasons for recurrences after immediate
      breast reconstruction in breast cancer patients. MATERIAL AND METHODS: The data
      of 79 patients undergoing immediate breast reconstruction between 1998 and 2001
      in Kuopio University Hospital were re-examined from both the local cancer
      register and the patient charts at the end of year 2003. RESULTS: There were five
      local recurrences (6.3%), one regional recurrence (1.2%), and three cases (3.8%)
      presented bone and/or visceral metastases. All recurrences except one (primary
      tumor noninvasive) appeared within the first two years after primary therapy.
      Young age and increasing size of the tumour were risk factors for distant or
      logoregional metastases. CONCLUSION: Immediate breast reconstruction is a safe
      procedure in breast cancer patients, but a multidisciplinary team is needed for
      careful patient selection.

PMID- 15865112
TI  - Liver operations in Sweden in 1987-99.
AB  - BACKGROUND AND AIMS: Liver surgery is developing with new techniques and
      treatment modalities. The aim of this study is to describe liver surgery over a
      long period of time in a country with a public health care system. PATIENTS AND
      METHOD: A register study including adult patients admitted for liver resection in
      Sweden (population 8.8 million) selected from the Inpatient Register 1987-99.
      Additional data were collected from the Swedish Cancer Register and the Cause of
      Death Register. Analyses of the patients, indications, mortality and causes of
      death are presented. RESULTS: 2,405 operations were performed (21 per million per
      year). The most frequent indication was colorectal metastases (27%). The 5-year
      survival after an operation for primary liver cancer and colorectal liver
      metastases was 27% and 26%, respectively. CONCLUSIONS: Few patients were admitted
      for liver operations compared to expected figures. The survival rates are in
      conformity with those previously published. With an increasing awareness of the
      relatively favourable prognosis and the introduction of new methods, the volume
      of liver operations will probably increase in Sweden.

PMID- 15865113
TI  - Is preoperative evaluation of the biliary tree necessary in uncomplicated
      gallstone disease? Results of a randomized trial.
AB  - AIM: To analyse if preoperative radiology is of value in patients with
      uncomplicated gallstone disease. MATERIAL: 312 patients intended for laparoscopic
      cholecystectomy were randomly allocated to undergo preoperative radiology
      (intravenous cholangiography or magnetic resonance cholangiography) or to a
      control group. Intraoperative cholangiography was not used routinely in either
      group. RESULTS: There was no bile duct injury and no difference in complication
      frequency between the two groups. The incidence of common bile duct stones was
      3.8% within the first postoperative year with no statistical difference between
      the two groups. CONCLUSIONS: Routine preoperative evaluation of the bile tree
      seems unnecessary before laparoscopic cholecystectomy in patients with
      uncomplicated gallstone disease.

PMID- 15865114
TI  - Quality of life and pain in patients with acute cholecystitis. Results of a
      randomized clinical trial.
AB  - BACKGROUND: Acute cholecystitis carries a higher risk of subsequent gallstone
      related events than symptomatic, non-complicated disease. However, it is largely
      unknown to what extent non-operative treatment will affect the patient's well
      being as no trial has studied the possible consequences on pain and quality of
      life. Our aim was to study in a randomized trial how observational treatment
      (watchful waiting) compared to cholecystectomy. METHODS: Sixty-four patients with
      acute cholecystitis were randomized to observation or cholecystectomy. All
      gallstone related events were registered and patients answered questionnaires on
      quality of life (PGWB and NHP) and pain (Pain score and VAPS) at randomization
      and at 6, 12 and 60 months later. RESULTS: Patients were followed-up for a median
      of 67 months. Ten of 33 patients (30%, 95% CI 15%-46%) patients randomized to
      observation and 27 of 31 (87%, 95% CI 75 %- 99%) of patients randomized to
      operation had a cholecystectomy. Twelve of 33 (36%, 95% CI 20%-53%) patients in
      the observation group had a gallstone related event compared to 6 of 31 (19%, 95%
      CI 5%-33%) patients in the operation group, but the difference was not
      significant. When patients were grouped according to randomization or actual
      operative outcome (+/- cholecystectomy), we did not find any significant
      differences in pain or quality of life measurements. CONCLUSION: Although
      conservative treatment of AC carried a certain but not significantly increased
      risk of subsequent gallstone related events, this did not influence the
      symptomatic outcome as assessed by quality of life and pain measurements. Thus,
      we argue that conservative (non-operative) treatment and observation of AC is an
      acceptable option and should at least be considered in elderly and frail
      patients.

PMID- 15865115
TI  - Fate of the rectum after colectomy with ileorectal anastomosis in ulcerative
      colitis.
AB  - OBJECTIVE: Aim of the study was to evaluate the cumulative success of colectomy
      and ileorectal anastomosis in 20 patients with ulcerative colitis. PATIENTS AND
      METHODS: Data were collected from patient histories and cumulative success was
      calculated by the Kaplan-Meier method. RESULTS: Seven of 20 (35%) ileorectal
      anastomoses were lost. Cumulative success rate was 84% at 5 years, 69% at 10
      years and 56% at 20 years. Most common indication for proctectomy was disabling
      proctitis. Other reasons for failure were postoperative ileal necrosis and
      persisting presacral infection. Patients with advanced colonic cancer managed
      relatively well with ileorectal anastomosis until death. No cases of rectal
      cancer were detected during postoperative follow-up but one moderate dysplasia
      was treated locally. CONCLUSION: Ileorectal anastomosis can be chosen for
      patients who are not suitable for ileoanal operation. Rectal endoscopies are
      mandatory postoperatively.

PMID- 15865116
TI  - Surgery for pilonidal disease.
AB  - BACKGROUND AND AIMS: Surgery for pilonidal disease carries a considerable risk of
      complications, recurrence, and cosmetic sequelae. The present study evaluates the
      four procedures performed in our institution. MATERIAL AND METHODS: Operations
      from 1999 through 2002 were retrospectively assessed. Cosmetic result and overall
      satisfaction were reported on visual analogue scales. RESULTS: Seventy-three
      procedures were performed in 71 patients: excision with open granulation in nine;
      excision and primary suture in 25; rhomboid plasty in 23; and lay-open in 16
      patients. Infections were as frequent after rhomboid plasty (40%) as after
      excision and primary suture (43%). Nineteen recurrences (26%) were observed
      during a median follow-up of 20 months, and the estimated five-year actuarial
      recurrence rate was 44%. Recurrence occurred in 1/9 (11%) after excision with
      granulation, in 4/23 (17%) after excision and suture, in 5/25 (20%) after
      rhomboid plasty, and in 9/16 patients (56%) after lay-open. The cosmetic result
      was satisfactory only in 22/53 (42%) patients; the result was poor in 16/53 (30%)
      patients. CONCLUSION: Results after surgery for pilonidal disease are modest and
      should be compared to conservative management in a randomised trial.

PMID- 15865117
TI  - Pneumatosis intestinalis--a pitfall for surgeons?
AB  - Pneumatosis intestinalis (PI) is characterized by multiple gas cysts in the wall
      of the gastrointestinal tract. Primary PI is extremely rare. In most of the cases
      PI is due to an underlying disease (traumatic and mechanical, inflammatory and
      autoimmune diseases, infectious and pulmonary diseases, drug induced,
      immunosuppression, transplantation, or neoplasm). A 69-year-old woman was treated
      with mixed connective tissue disease and PI twice operatively and once
      conservatively in our department. Review of the English literature showed 13 more
      cases of PI with underlying mixed connective tissue disease. Most published cases
      of pneumatosis intestinalis with radiological finding of pneumoperitoneum were
      treated conservatively and should have not been considered as a reason for
      surgery. Therefore, the treatment of PI can present as a major dilemma for the
      surgeon.

PMID- 15865118
TI  - The profile of leg symptoms, clinical disability and reflux in legs with
      previously operated varicose disease.
AB  - PURPOSE: It is difficult to assess the severity and location of venous
      insufficiency in legs with recurrent varicose disease. This present purpose was
      to evaluate the distribution of reflux and the diagnostic role of current
      classifications in a consecutive series of legs with previously operated varicose
      disease. METHODS: A total of 90 legs in a cohort of 66 patients were included.
      The examination comprised CEAP clinical class, clinical disability score (CDS)
      and leg symptoms. Colour-flow duplex imaging (CFDI) was used to observe reflux in
      deep and superficial veins. Details of prior surgery were assessed. RESULTS: The
      site of superficial reflux was at the groin in 58% (recurrent or residive vein
      trunk or unoperated great saphenous vein), and the rate in the popliteal fossa
      was 11% (unoperated short saphenous vein). In 58% of the legs presenting
      superficial reflux at groin level, previous surgery at the saphenofemoral
      junction was noted. A sensation of pain was observed in 74% of the legs,
      sensation of oedema in 64%, itching in 26 %, and night cramps in 8%,
      respectively. Only itching was significantly infrequent in uncomplicated (CEAP C
      2-3) legs, and in legs with local reflux was restricted to vein tributaries.
      Higher CDS (classes 2-3) were significantly more frequent among complicated legs
      (CEAP clinical class C2-3: 22% versus CEAP clinical class C4-6: 77%; p < 0.005).
      A similar situation was noted when legs with only local reflux were compared to
      those with more severe reflux (local reflux: 7% versus severe reflux: 48%; p <
      0.005). CONCLUSIONS: Superficial reflux is frequently detected at groin level
      despite prior surgery. Unstructured evaluation of leg symptoms is not beneficial.
      Clinical disability scores associate well with the severity of the venous
      disease.

PMID- 15865119
TI  - Comparison between flutter valve drainage bag and underwater seal device for
      pleural drainage after lung surgery.
AB  - AIM OF THE STUDY: The purpose of the present study was to compare the use of a
      conventional underwater seal device with suction and a flutter valve drainage bag
      for pleural drainage after lung surgery. PATIENTS AND METHODS: Altogether 59
      patients undergoing elective lung surgery except pneumonectomy between February
      2001 and April 2002 were prospectively randomized to receive postoperative
      pleural drainage by 28F chest tube(s) attached to underwater seal device placed
      on negative pressure of 15 cm of water or flutter valve drainage bag. Following
      withdrawal of four patients from the study, 55 patients were evaluated (31
      patients in the underwater seal device group and 24 patients in the flutter valve
      drainage bag group). RESULTS: In the conventional underwater seal device group
      the mean drainage time was 2.6 (SD +/- 2.0) days and in the flutter valve
      drainage bag group the mean drainage time was 3.3 days (SD +/- 4.0); difference 
      0.8, 95% confidence interval (CI) -2.4 to 0.9. The mean length of hospitalization
      in the surgical ward was 3.6 (SD +/- 2.7) and 4.1 (SD +/- 4.4) days respectively
      (difference -0.5, 95% CI -2.5 to 1.4). CONCLUSIONS: The results of this study
      suggest that flutter valve drainage system is a safe and feasible alternative in
      managing postoperative air leaks and haemorrhage after lung surgery other than
      pneumonectomy if air leaks are not extremely massive.

PMID- 15865120
TI  - Four or twelve months' follow-up in the evaluation of functional outcome after
      hip fracture surgery?
AB  - BACKGROUND AND AIMS: As a rule, follow-up for at least one year is recommended
      for fracture studies. This is considered the shortest reliable interval. Still,
      in the case of hip fractures of the elderly, shorter follow-up might be more
      practical, since the life expectancy of these patients is often short. The aim of
      this study was to see if a short four months follow-up period would be acceptable
      in hip fracture surveys. MATERIAL AND METHODS: Information on 196 consecutive non
      pathological hip fracture patients aged 50 years or over (mean 79 years) was
      collected using a standardised hip fracture audit concentrating on functional
      measurements at admission and at four and twelve months' follow-ups. RESULTS: 167
      patients were alive at four months and 152 and at one year. The patients who died
      between four and twelve months had poorer functional capacity in the four- month
      evaluation than those who survived one year. The analysis of repeated measures,
      including only the patients alive at the last follow-up, showed that residential
      status, use of walking aids and 6 out of 10 and ADL variables (bathing,
      toileting, shopping, household activities, doing laundry, banking) did not change
      significantly. Walking ability and the rest 4 ADL variables (dressing, eating,
      food preparation, use of transportation) improved and pain decreased.
      CONCLUSIONS: Due to high mortality and age-related deterioration of functioning,
      no steady state i.e. "final result" is ever reached after hip fracture in the
      elderly. Four-month follow-up is justified as the shortest possible period,
      because the socioeconomically most important variable, i.e. place of living, and
      most of the ADL functions do not change significantly after that.

PMID- 15865121
TI  - Gamma irradiation and ethylene oxide in the sterilization of native reindeer bone
      morphogenetic protein extract.
AB  - BACKGROUND AND AIMS: For human use, it is necessary to sterilize bone
      morphogenetic proteins (BMPs), in order to reduce the risk of infections and
      associated complications. We compared the effects of ethylene oxide and gamma
      irradiation in the sterilization of native reindeer BMP extract with regard to
      bone induction in the Balb/C mouse thigh muscle pouch model. MATERIALS AND
      METHODS: BMP extract, sterilized with ethylene oxide gas (Steri-Vac 4XL,
      temperature 29 degrees C, exposure time 4 h, ethylene oxide concentration 860
      mg/l), or gamma irradiation at doses of 3.15 MRad was administered in implants
      containing 5 or 10 mg of BMP extract with collagen carrier. Non-sterilized
      collagen implants served as controls. New bone formation was evaluated based on
      the incorporation of Ca45 and radiographically three weeks after implantation.
      RESULTS: The collagen was not able to induce new bone visible in radiographs. The
      mean Ca45 incorporation in the gamma sterilized group containing 5 mg of BMP
      extract was 30% (p = 0.04) and that containing 10 mg of BMP extract was 60% (p =
      0.02) higher than seen in the corresponding ethylene oxide sterilized groups. The
      mean new bone areas were 45% higher in the gamma sterilized groups than in the
      corresponding ethylene oxide sterilized groups, but the differences were not
      significant. The mean optical density of new bone in the gamma sterilized group
      containing 5 mg of BMP extract was 75% (p = 0.00) and in that containing 10 mg of
      BMP extract was 70% (p = 0.00) higher than seen in the corresponding ethylene
      oxide sterilized groups. CONCLUSION: Native reindeer BMP extract is more
      sensitive to the effects of ethylene oxide gas sterilization than gamma
      irradiation. These results suggest that gamma irradiation is recommendable for
      the sterilization of BMP extracts.

PMID- 15865122
TI  - Dupuytren's contracture; increased cellularity--proliferation, is there equality?
AB  - BACKGROUND: Dupuytren's disease is a chronic inflammatory process which causes
      contractures of the fingers by shortening and thickening the palmar fascia.
      During the proliferative phase, fibroblasts transform into myofibroblasts
      apparently under the influence of several different factors. The disease usually
      develops slowly, but in some patients it tends to develop aggressively. The
      pathogenesis of Dupuytren's disease remains unsolved. In this study, we analyzed
      some histological characteristics that seem to predict rapid recurrence. MATERIAL
      AND METHODS: 21 patients were divided into two groups. In 11 patients the disease
      was classified as aggressive because it had recurred within two years after an
      operation. In 10 cases it was non-aggressive, as no recurrence had been seen.
      Five control samples were taken from healthy palmar aponeurosis. The differences
      in cellularity, collagen, Ki-67, MSA, alpha-SMA and tenascin between the
      specimens were analyzed using immunohistochemistry. RESULTS: Alpha-SMA and Ki-67
      were present more often in the aggressive specimens. Immunohistochemical
      stainings for macrophages and lymphocytes were negative. CONCLUSION: There may be
      differences in the histology and/or immunohistochemical appearance of
      pathological palmar connective tissue cords in aggressive and normal Dupuytren's
      disease. Further studies are needed to elucidate the pathogenesis of this
      disease.

PMID- 15865123
TI  - Etiology and outcome of burns in Tabriz, Iran. An analysis of 2963 cases.
AB  - BACKGROUND AND AIMS: Burn injuries still produce a significant morbidity and
      mortality in Iran. A 3-year retrospective review of burn victims hospitalized at
      a major burn center was conducted to determine the etiology and outcome of
      patients in Tabriz. MATERIAL AND METHODS: Two thousand nine hundred sixty + three
      patients were identified and stratified by age, sex, burn size, presence or
      absence of inhalation injury, cause of burn. There is one burn center in the East
      Azarbygan province serving 3.3 million people over an area of 47,830 sq.km.
      RESULTS: The overall incidence rates of hospitalization and death were 30.5% and
      5.6% per 100000 person years. The mean patient age was 22 years, and the male:
      female ratio was 1.275. There were 555 deaths altogether (18.7%). The highest
      incidence of burns was in the 1-9 age group (29.2%). Patients with less than 40
      percent of burned surface constituted 79.8% of injuries. The most common cause of
      burns was kerosene accident in adults and scald injuries in children. The mean
      length of hospitalization was 13 days. The mean body surface area burned was
      larger with higher mortality in females than in males (p < 0.001). Inhalation
      injuries were strongly associated with large burns and were present in all flame
      burn fatalities. CONCLUSION: In our opinion, social factors are the main drive
      leading to an unacceptably high rate of burn injuries in our societies. Most of
      the burn injuries were caused by domestic accidents and were, therefore,
      preventable; educational programs might reduce the incidence of burn injuries.

PMID- 15865124
TI  - Force enhancement following stretch of activated muscle: critical review and
      proposal for mechanisms.
AB  - Force enhancement is an acknowledged and well-accepted mechanical property of
      skeletal-muscle contraction. It occurs in isometric, steady-state contractions
      that are preceded by stretch of the activated muscle. Force enhancement increases
      with increasing magnitudes of stretch, is long lasting, but can be abolished by
      deactivation of a muscle just long enough for force to drop to zero, and is
      associated with an increase in passive force. The mechanisms underlying force
      enhancement are not known. One of the classic mechanisms for force enhancement is
      reviewed, and a new mechanism that is based on an active and a passive component
      is introduced. The passive component of force enhancement is tentatively
      associated with the molecular spring titin, and the active component is
      associated with an increase in the proportion of attached cross-bridges caused by
      a decrease in the cross-bridge detachment rate. The review is completed by the
      proposal of some questions and selected experiments that would test the proposed
      mechanisms in a rigorous way.

PMID- 15865125
TI  - Radiograph-based femur morphing method.
AB  - Many applications in orthopaedic surgery require the creation of personalised
      design models that can serve as the basis for navigation in computer aided
      surgery systems or be used to create a personalised model to perform structural
      analysis during pre-operative planning or post-operative follow-up. The paper
      introduces a method for developing a three-dimensional (3D) patient-specific
      model of a femur bone from an antero-posterior radiograph. A generic femur was
      employed and was altered on the basis of bone boundaries visible on radiographs.
      Morphological errors were evaluated against 3D models obtained from computed
      tomography (CT) scans. When only the antero-posterior radiograph was used, the
      average radius estimation error was 4.8 mm, the average percentage area
      estimation error was 14%, and the average percentage estimation error for
      inertial moments was 15%. If both the medial-lateral and the anterior-posterior
      radiographs were used, these errors were 2.0 mm, 5% and 7%, respectively. The
      procedure described can be profitably employed whenever CT scans are not
      available, such as during a retrospective analysis, or when CT scans cannot be
      justified because of X-ray exposure and cost considerations.

PMID- 15865126
TI  - Robust non-homomorphic approach for speckle reduction in medical ultrasound
      images.
AB  - Most existing wavelet-based image denoising techniques are developed for additive
      white Gaussian noise. In applications to speckle reduction in medical ultrasound
      (US) images, the traditional approach is first to perform the logarithmic
      transform (homomorphic processing) to convert the multiplicative speckle noise
      model to an additive one, and then the wavelet filtering is performed on the log
      transformed image, followed by an exponential operation. However, this non-linear
      operation leads to biased estimation of the signal and increases the
      computational complexity of the filtering method. To overcome these drawbacks, an
      efficient, non-homomorphic technique for speckle reduction in medical US images
      is proposed. The method relies on the true characterisation of the marginal
      statistics of the signal and speckle wavelet coefficients. The speckle component
      was modelled using the generalised Nakagami distribution, which is versatile
      enough to model the speckle statistics under various scattering conditions of
      interest in medical US images. By combining this speckle model with the
      generalised Gaussian signal first, the Bayesian shrinkage functions were derived
      using the maximum a posteriori (MAP) criterion. The resulting Bayesian processor
      used the local image statistics to achieve soft-adaptation from homogeneous to
      highly heterogeneous areas. Finally, the results showed that the proposed method,
      named GNDShrink, yielded a signal-to-noise ratio (SNR) gain of 0.42dB over the
      best state-of-the-art despeckling method reported in the literature, 1.73dB over
      the Lee filter and 1.31dB over the Kaun filter at an input SNR of 12.0dB, when
      tested on a US image. Further, the visual comparison of despeckled US images
      indicated that the new method suppressed the speckle noise well, while preserving
      the texture and organ surfaces.

PMID- 15865127
TI  - High-resolution 3D scaffold model for engineered tissue fabrication using a rapid
      prototyping technique.
AB  - Rapid prototyping, automatic image processing (computer-aided design (CAD)) and
      computer-aided manufacturing techniques are opening new and interesting prospects
      for medical devices and tissue engineering, especially for hard tissues such as
      bone. The development of a bone high-resolution scaffold prototype using these
      techniques is described. The results testify to the fidelity existing between
      microtomographic reconstruction and CAD. Furthermore, stereolithographic
      manufacturing of this scaffold, which possesses a high degree of similarity to
      the starting model as monitored by morphological evaluations (mean diameter 569
      +/- 147 microm), represents a promising result for regenerative medicine
      applications.

PMID- 15865128
TI  - Cell calcium oscillations: the origin of their variability.
AB  - Oscillation in calcium levels in the cytoplasm of individual cells has been
      observed experimentally to consist of a series of spikes and plateaux of
      differing amplitudes and inter-peak intervals. On the other hand, mathematical
      models based on known biochemical reaction kinetic behaviours predict, in the
      main, limit cycle behaviour. Chaotic solutions do not mimic the observed
      variability, and so another solution was sought by the introduction of filtered
      noise into some of the kinetic coefficients. Some of the variability can be
      predicted from this mechanism, but it is likely that other sources contribute to
      this as well.

PMID- 15865129
TI  - Breath sound changes associated with malpositioned endotracheal tubes.
AB  - Endotracheal tubes (ETTs) are used to establish airway access in patients with
      ventilatory failure and during general anaesthesia. Tube malpositioning can
      compromise respiratory function and can be associated with increased morbidity
      and mortality. Clinical assessment of ETT position normally involves chest
      auscultation, which is highly skill-dependent and can be misleading. The
      objective of this pilot study was to investigate breath sound changes associated
      with ETT malpositioning. Breath sounds were acquired in six human subjects over
      each hemithorax and over the epigastrium for tracheal, bronchial and oesophageal
      intubations. When the ETT was in the oesophagus, the acoustic energy ratio
      between epigastrium and chest surface increased in all subjects (p < 0.04). In
      addition, ETT placement in the right mainstem bronchus decreased the acoustic
      energy ratio between the left and right hemithoraxes in all subjects (p < 0.04).
      A baseline measurement of this energy ratio was needed for bronchial intubation
      identification. However, using this ratio after bandpass filtering (200-500 Hz)
      did not require a baseline value, which would increase the utility of this method
      for initial ETT placement. These results suggest that computerised analysis of
      breath sounds may be useful for assessment of ETT positioning. More studies are
      needed to test the feasibility of this approach further.

PMID- 15865130
TI  - Detection of the third heart sound using a tailored wavelet approach: method
      verification.
AB  - Heart sounds can be considered as mechanical fingerprints of myocardial function.
      The third heart sound normally occurs in children but disappears with maturation.
      The sound can also appear in patients with heart failure. The sound is
      characterised by its low-amplitude and low-frequency content, which makes it
      difficult to identify by the traditional use of the stethoscope. A wavelet-based
      method has recently been developed for detection of the third heart sound. This
      study investigated if the third heart sound could be identified in patients with
      heart failure using this detection method. The method was also compared with
      auscultation using conventional phonocardiography and with characterisation of
      the patients with echocardiography. In the first study, 87% of the third heart
      sounds were detected using the wavelet method, 12% were missed, and 6% were false
      positive. In study 2, the wavelet-detection method identified 87% of the patients
      using the third heart sound, and regular phonocardiography identified two (25%)
      of the subjects.

PMID- 15865131
TI  - Automatic optimum order selection of parametric modelling for the evaluation of
      abnormal intra-QRS signals in signal-averaged electrocardiograms.
AB  - Abnormal intra-QRS potentials (AIOPs) in signal-averaged electrocardiograms have
      been proposed as a risk evaluation index for ventricular arrhythmias. The purpose
      of the paper was to develop an automatic algorithm for selecting the optimum
      parametric model order in the analysis of AIOPs to make the modelling approach
      clinically more feasible. A total of 130 normal Taiwanese subjects and 87
      patients with ventricular premature contractions and 23 with sustained
      ventricular tachycardia were recruited. The unpredictable AIQP signal was
      estimated from the modelling residual. The cross-correlation coefficient between
      the original signal and the ORS estimate was employed to evaluate the accuracy of
      the estimate. A pre-selected threshold cross-correlation coefficient of 0.9999
      was used to determine the optimum order. The mean AIQP in lead Y for ventricular
      tachycardia patients was 3.9 microV, which was significantly smaller than 4.9
      microV for ventricular premature contraction patients (p < 0.01) and 6.3 microV
      for normal subjects (p < 0.001). The linear combination of AIQP in lead Y and the
      time-domain parameter RMS40 provided the best global performance (the area under
      the receiver operating characteristic curve was 89.1%). A higher risk of
      ventricular arrhythmias was associated with lower AIQP in lead Y, and the
      automatic modelling algorithm improved the clinical feasibility of AIQP analysis.

PMID- 15865132
TI  - Impedance-gradient electrode reduces skin irritation induced by transthoracic
      defibrillation.
AB  - A new type of disposable external defibrillation electrode has been developed to
      reduce the skin irritation commonly associated with defibrillation and
      synchronised cardioversion. This design employs an impedance gradient to reduce
      the proportion of current delivered to the electrode periphery. The temperature
      distribution under the new electrode was compared with that of four other types
      of commercially available electrodes after repeated high-energy biphasic
      defibrillation discharges to domestic swine. Skin temperature distributions were
      acquired using non-invasive thermography. Measurements of the maximum temperature
      rise at each electrode site, taken 3.6s after the fifth defibrillation discharge,
      demonstrated that the new impedance-gradient electrode produced 50-60% less skin
      heating than two of the three uniform-impedance electrode designs. Histological
      examination of erythematous sites excised 24 h after defibrillation quantified
      the associated skin damage using a scoring protocol developed for this study. In
      contrast to previous studies, histological examinations demonstrated second
      degree skin burns following defibrillation. The new electrode design, however,
      induced 44-46% less skin damage than two of the traditional uniform-impedance
      electrodes.

PMID- 15865133
TI  - Forecasting epilepsy from the heart rate signal.
AB  - Information contained in the R-R interval series, specific to the pre-ictal
      period, was sought by applying an unsupervised fuzzy clustering algorithm to the
      N-dimensional phase space of N consecutive interval durations or the absolute
      value of duration differences. Data sources were individual, complex partial
      seizures of temporal-lobe epileptics and generalised seizures of rats rendered
      epileptic with hyperbaric oxygen. Forecasting success was 86% and 82% (zero false
      positives in resistant rats), respectively, at times ranging from 10 min to 30 s
      prior to seizure onset Although certain forecasting clusters predominated in the
      patient group and different ones predominated in the animal group, forecasting on
      the whole was seizure-specific. The high prediction sensitivity of this method,
      which matches that of EEG-based methods, seems promising. It is believed that an
      on-line version of the algorithm, trained on each patient's peri-ictal ECG, could
      serve as a basis for a simple seizure alarm system.

PMID- 15865134
TI  - Detection of needle puncture to blood vessel using puncture force measurement.
AB  - Although blood sampling is frequently performed, a system to take blood samples
      automatically has not yet been developed. In the paper, as a first step towards
      automatic blood sampling, an examination of an automatic method for puncturing
      blood vessels is described. The force waveforms produced by puncturing rabbit ear
      veins were measured. A characteristic peak, possibly associated with the needle
      piercing the vessel wall, was observed in each waveform of ten successful cases
      of 14 trials. An algorithm that allowed the detection of this peak was developed,
      and parameters of a filter to improve the accuracy of the algorithm were
      determined. Using this algorithm, automatic needle punctures were performed in a
      rabbit ear vein and then were simulated using the data derived from manual needle
      puncture on four other rabbits. The results gave 30 fully successful cases of 33
      trials of needle puncture and showed that measurement of the puncture force may
      be important for automatic needle puncture of blood vessels.

PMID- 15865135
TI  - Extraction of gastric slow waves from electrogastrograms: combining independent
      component analysis and adaptive signal enhancement.
AB  - The electrogastrogram (EGG), a cutaneous measurement of gastric electrical
      activity, is a mixture of gastric slow waves and noise. To detect the propagation
      of gastric slow waves, it is desired to obtain gastric slow waves in each of
      multichannel EGGs. Recently, independent component analysis (ICA) has shown its
      efficiency in separating the gastric slow wave from noisy multichannel EGGs.
      However, this method is not able to recover gastric slow waves in each of the
      multichannel EGGs. In this paper, a two-stage combined method was proposed for
      extracting gastric slow waves. First, ICA was performed to separate the gastric
      slow wave component from noisy multichannel EGGs. Second, adaptive signal
      enhancement with a reference input derived by the ICA in the first stage was
      employed to extract gastric slow waves in each channel. Quantitative analysis
      showed that, with the proposed method, the maximum root-mean-square error between
      the estimated time lag and its theoretical value in the simulations was only
      0.65. The results from real EGG data demonstrated that the combined method was
      able to extract gastric slow waves from individual channels of EGGs which are
      important to identify the slow wave propagation. Therefore, the proposed method
      can be used to detect propagation of gastric slow waves from multichannel EGGs.

PMID- 15865136
TI  - Right-left correlation of the sympathetically induced fluctuations of
      photoplethysmographic signal in diabetic and non-diabetic subjects.
AB  - Photoplethysmography (PPG) records the cardiac-induced changes in tissue blood
      volume by light-transmission measurements. The baseline and amplitude of the PPG
      signal show very low-frequency (VLF) spontaneous fluctuations, which are mediated
      by the sympathetic nervous system, and high correlation between right and left
      extremities of healthy subjects. As sympathetic neuropathy is one of the diabetic
      complications, the right-left correlation of the PPG fluctuations was examined in
      diabetic patients. The PPG signal was simultaneously measured in the two index
      fingers and the two second toes of 35 diabetic patients and 33 non-diabetic
      subjects. For each PPG pulse, the baseline and amplitude were determined, and the
      right-left correlation coefficients of the VLF fluctuations in the baseline and
      amplitude were derived. The VLF fluctuations in the baseline showed high right
      left correlation, both for fingers (0.93 +/- 0.05) and toes (0.93 +/- 0.06), for
      the non-diabetic subjects, and significantly lower correlation (0.78 +/- 0.22 and
      0.84 +/- 0.17, respectively) for the diabetic patients. Similar results were
      obtained for the amplitude VLF fluctuations. The right-left correlation
      coefficients for diabetic patients decreased with the disease duration for the
      toe baseline and toe amplitude fluctuations and correlated with heart rate
      response to deep breathing for the finger baseline and toe amplitude
      fluctuations. The right-left correlation coefficients of the PPG fluctuations
      provide a simple and convenient means for assessing the adequacy of the
      sympathetic nervous system function.

PMID- 15865137
TI  - Estimation of Young's modulus and Poisson's ratio of soft tissue from indentation
      using two different-sized indentors: finite element analysis of the finite
      deformation effect.
AB  - Young's modulus and Poisson's ratio of a tissue can be simultaneously obtained
      using two indentation tests with two different sized indentors in two
      indentations. Owing to the assumption of infinitesimal deformation of the
      indentation, the finite deformation effect of indentation on the calculated
      material parameters was not fully understood in the double indentation approach.
      However, indentation tests with infinitesimal deformation are not practical for
      the measurement of real tissues. Accordingly, finite element models were
      developed to simulate the indentation with different indentor diameters and
      different deformation ratios to investigate the finite deformation effect of
      indentation. The results indicated that Young's modulus E increased with the
      increase in the indentation deformation w, if the finite deformation effect of
      indentation was not considered. This phenomenon became obvious when Poisson's
      ratio v approached 0.5 and/or the ratio of indentor radius and tissue thickness
      a/h increased. The calculated Young's modulus could be different by 23% at 10%
      deformation in comparison with its real value. The results also demonstrated that
      the finite deformation effect to indentation on the calculation of Poisson's
      ratio v was much smaller. After the finite deformation effect of indentation was
      considered, the error of the calculated Young's modulus could be controlled
      within 5% (a/h = 1) and 2% (a/h = 2) for deformation up to 10%.

PMID- 15865138
TI  - Analysis and decomposition of accelerometric signals of trunk and thigh obtained
      during the sit-to-stand movement.
AB  - Piezoresistive accelerometer signals are frequently used in movement analysis.
      However, their use and interpretation are complicated by the fact that the signal
      is composed of different acceleration components. The aim of the study was to
      obtain insight into the components of accelerometer signals from the trunk and
      thigh segments during four different sit-to-stand (STS) movements (self-selected,
      slow, fast and fullflexion). Nine subjects performed at least six trials of each
      type of STS movement. Accelerometer signals from the trunk and thigh in the
      sagittal direction were decomposed using kinematic data obtained from an opto
      electronic device. Each acceleration signal was decomposed into gravitational and
      inertial components, and the inertial component of the trunk was subsequently
      decomposed into rotational and translational components. The accelerometer
      signals could be reliably reconstructed: mean normalised root mean square (RMS)
      trunk: 6.5% (range 3-12%), mean RMS thigh: 3% (range 2-5%). The accelerometric
      signals were highly characteristic and repeatable. The influence of the inertial
      component was significant, especially on the timing of the specific event of
      maximum trunk flexion in the accelerometer signal. The effect of inertia was
      larger in the trunk signal than in the thigh signal and increased with higher
      speeds. The study provides insight into the acceleration signal, its components
      and the influence of the type of STS movement and supports its use in STS
      movement analysis.

PMID- 15865139
TI  - Measuring orientation of human body segments using miniature gyroscopes and
      accelerometers.
AB  - In the medical field, there is a need for small ambulatory sensor systems for
      measuring the kinematics of body segments. Current methods for ambulatory
      measurement of body orientation have limited accuracy when the body moves. The
      aim of the paper was to develop and validate a method for accurate measurement of
      the orientation of human body segments using an inertial measurement unit (IMU).
      An IMU containing three single-axis accelerometers and three single-axis
      micromachined gyroscopes was assembled in a rectangular box, sized 20 x 20 x 30
      mm. The presented orientation estimation algorithm continuously corrected
      orientation estimates obtained by mathematical integration of the 3D angular
      velocity measured using the gyroscopes. The correction was performed using an
      inclination estimate continuously obtained using the signal of the 3D
      accelerometer. This reduces the integration drift that originates from errors in
      the angular velocity signal. In addition, the gyroscope offset was continuously
      recalibrated. The method was realised using a Kalman filter that took into
      account the spectra of the signals involved as well as a fluctuating gyroscope
      offset. The method was tested for movements of the pelvis, trunk and forearm.
      Although the problem of integration drift around the global vertical continuously
      increased in the order of 0.50 degrees s(-1), the inclination estimate was
      accurate within 3 degrees RMS. It was shown that the gyroscope offset could be
      estimated continuously during a trial. Using an initial offset error of 1 rad s(
      1), after 2 min the off-set error was roughly 5% of the original offset error.
      Using the Kalman filter described, an accurate and robust system for ambulatory
      motion recording can be realised.

PMID- 15865140
TI  - Electrotactile perception of scatterplots on the fingertips and abdomen.
AB  - A comparison of auditory and visual perception of scatterplots showed similar
      correlation estimation performance in both modalities. The present study
      replicated this experiment using electrotactile (electrocutaneous) presentation
      of scatterplots on the fingertips and abdomen, as well as visual presentation.
      The correlation estimation task resulted in a slightly poorer performance on
      electrotactile scatterplots (abdomen r = +0.847; fingertip r = +0.723) compared
      with the previous Flowers auditory displays (r = +0.91). There were similar
      levels of performance in the visual (control) condition in both the studies (r
      for both approx. +0.91). The performance in the correlation estimation task was
      similar across the two electrotactile displays, with perhaps a slight, but not
      significant (p = 0.077), advantage for the abdominal array. However, a
      preliminary digit identification task on both displays produced a better
      performance on the fingertip display (p < 0.05), suggesting that the relative
      performance of the two displays may be task specific. The present results
      demonstrate electrotactile perception of complex graphs and provide useful
      information for improving future versions of tactile displays.

PMID- 15865141
TI  - Removal of eye blinking artifact from the electro-encephalogram, incorporating a
      new constrained blind source separation algorithm.
AB  - A robust constrained blind source separation (CBSS) algorithm has been developed
      as an effective means to remove ocular artifacts (OAs) from electro
      encephalograms (EEGs). Currently, clinicians reject a data segment if the patient
      blinked or spoke during the observation interval. The rejected data segment could
      contain important information masked by the artifact. In the CBSS technique, a
      reference signal was exploited as a constraint. The constrained problem was then
      converted to an unconstrained problem by means of non-linear penalty functions
      weighted by the penalty terms. This led to the modification of the overall cost
      function, which was then minimised with the natural gradient algorithm. The
      effectiveness of the algorithm was also examined for the removal of other
      interfering signals such as electrocardiograms. The CBSS algorithm was tested
      with ten sets of data containing OAs. The proposed algorithm yielded, on average,
      a 19% performance improvement over Parra's BSS algorithm for removing OAs.

PMID- 15865142
TI  - Real-time ocular artifact suppression using recurrent neural network for electro
      encephalogram based brain-computer interface.
AB  - The paper presents an adaptive noise canceller (ANC) filter using an artificial
      neural network for real-time removal of electro-oculogram (EOG) interference from
      electro-encephalogram (EEG) signals. Conventional ANC filters are based on linear
      models of interference. Such linear models provide poorer prediction for
      biomedical signals. In this work, a recurrent neural network was employed for
      modelling the interference signals. The eye movement and eye blink artifacts were
      recorded by the placing of an electrode on the forehead above the left eye and an
      electrode on the left temple. The reference signal was then generated by the data
      collected from the forehead electrode being added to data recorded from the
      temple electrode. The reference signal was also contaminated by the EEG. To
      reduce the EEG interference, the reference signal was first low-pass filtered by
      a moving averaged filter and then applied to the ANC. Matlab Simulink was used
      for real-time data acquisition, filtering and ocular artifact suppression.
      Simulation results show the validity and effectiveness of the technique with
      different signal-to-noise ratios (SNRs) of the primary signal. On average, a
      significant improvement in SNR up to 27 dB was achieved with the recurrent neural
      network. The results from real data demonstrate that the proposed scheme removes
      ocular artifacts from contaminated EEG signals and is suitable for real-time and
      short-time EEG recordings.

PMID- 15865143
TI  - Unconstrained detection of respiration rhythm and pulse rate with one under
      pillow sensor during sleep.
AB  - A completely non-invasive and unconstrained method is proposed to detect
      respiration rhythm and pulse rate during sleep. By employing wavelet
      transformation (WT), waveforms corresponding to the respiration rhythm and pulse
      rate can be extracted from a pulsatile pressure signal acquired by a pressure
      sensor under a pillow. The respiration rhythm was obtained by an upward zero
      crossing point detection algorithm from the respiration-related waveform
      reconstructed from the WT 2(6) scale approximation, and the pulse rate was
      estimated by a peak point detection algorithm from the pulse-related waveform
      reconstructed from the WT 2(4) and 2(5) scale details. The finger photo-electric
      plethysmogram (FPP) and nasal thermistor signals were recorded simultaneously as
      reference signals. The reference pulse rate and respiration rhythm were detected
      with the peak and upward zero-crossing point detection algorithm. This method was
      verified using about 24 h of data collected from 13 healthy subjects. The results
      showed that, compared with the reference data, the average error rates were 3.03%
      false negative and 1.47% false positive for pulse rate detection in the extracted
      pulse waveform. Similarly, 4.58% false negative and 3.07% false positive were
      obtained for respiration rhythm detection in the extracted respiration waveform.
      This study suggests that the proposed method is suitable, in sleep monitoring,
      for the diagnosis of sleep apnoea or sudden death syndrome.

PMID- 15865144
TI  - Decolourisation of reactive textile dyes Drimarene Blue X3LR and Remazol
      Brilliant Blue R by Funalia trogii ATCC 200800.
AB  - Decolourisation of reactive dyes Drimarene Blue X3LR and Remazol Brilliant Blue R
      by white rot fungi Funalia trogii was studied under static conditions. The effect
      of various conditions such as mycelial age, initial dye and glucose
      concentrations on decolourisation were also investigated. Decolourisation
      activity of F. trogii was compared with Phanerochaete chrysosporium known as test
      microorganism. It was found that 7-day-old cultures were more effective than 5
      day-old cultures of F. trogii for decolourisation of these dyes. Decolourisations
      by F. trogii of both dyes were increased with glucose concentration decreasing.
      In contrast, decolourisations by P. chrysosporium were decreased. F. trogii
      decolourised 92-98% of both dyes within 4-10 h. However, P. chrysosporium
      partiallydecolourised (11-20%) these dyes during 10 days incubation period under
      the same conditions.

PMID- 15865145
TI  - Process inhibition due to organic acids in fed-batch composting of food waste-
      influence of starting culture.
AB  - Inhibition of the degradation during low pH conditions has been observed in fed
      batch composting systems. To analyse this phenomenon, fed-batch composting of
      food waste with different amounts of starting culture was examined in laboratory
      reactor experiments. Changes in temperature, carbon dioxide evolution, pH,
      solids, ash and short chain organic acids were measured. In reactors with a daily
      feed rate of 24% or less of the starting culture, thermophilic temperatures
      occurred and the pH and carbon dioxide evolution were high and stable after a
      starting period of 4-5 days. In reactors with a daily feed rate of 48% or more of
      the starting culture the composting process failed, as the pH dropped below 6 and
      remained there and the temperature and carbon dioxide evolution were low. It was
      concluded that the use of adequate amounts of starting culture consisting of
      active compost can efficiently prevent low pH conditions and process inhibition
      in fed-batch composting of food waste.

PMID- 15865146
TI  - Enhancement of anaerobic carbon tetrachloride biotransformation in methanogenic
      sludge with redox active vitamins.
AB  - Carbon tetrachloride (CT) is an important groundwater pollutant which is only
      subject to biotransformation in the absence of oxygen. The anaerobic
      biotransformation of CT is influenced by electron shuttling compounds. The
      purpose of this study was to evaluate the impact of redox active vitamins on CT
      (100 microM) metabolism in a methanogenic sludge consortium (0.5 g VSS l(-1))
      supplied with volatile fatty acids as electron donor (0.2 g COD l(-1)). The redox
      active vitamins, tested at concentrations ranging from 0.5 to 20 microM, were
      riboflavin (RF) and two forms of vitamin B12, cyanocobalamin (CNB12) and
      hydroxycobalamin (HOB12), and these were compared with a redox mediating quinone,
      anthraquinone-2,6-disulfonate (AQDS). Substoichiometric concentrations of RF,
      CNB12, HOB12 at molar ratios of vitamin: CT as low as 0.005 significantly
      increased rates of CT-bioconversion. These are the lowest molar ratios of vitamin
      B12 reported having an impact on dechlorination. Additionally, this study
      constitutes the first report of RF having a role in reductive dechlorination. At
      molar ratios of 0.1 vitamin: CT, RF, CNB12, HOB12 increased the first order rate
      constant of CT bioconversion by 4.0-, 13.3-and 13.6-fold, respectively. The redox
      active vitamins also enhanced the rates of abiotic CT conversion in heat killed
      sludge treatments, but the rates were approximately 4- to 5-fold lower than the
      corresponding vitamin enhanced rates of biological CT conversion. The addition of
      CNB12 or HOB12 to the live methanogenic sludge consortium increased the yield of
      inorganic chloride (Cl-) from CT-converted. Chloroform was a transient
      intermediate in CNB12 or HOB12 supplemented cultures. In contrast, the addition
      of RF increased the yield of chloroform from CT-converted. Taken as a whole the
      results clearly demonstrate that very low concentrations of redox active vitamins
      could potentially play an important role in accelerating the anaerobic the
      bioremediation of CT as well as influencing the proportions of biotransformation
      products formed.

PMID- 15865147
TI  - Degradation of nitrocellulose by fungi.
AB  - Three lignocellulolytic fungi, Trametes versicolor, Pleurotus ostreatus, and
      Coprinus cinereus, and two cellulolytic fungi Trichoderma reesei and Chaetomium
      elatum were tested for their ability to degrade nitrocellulose. They were
      provided with different carbon and nitrogen sources in liquid cultures.
      Nitrocellulose (N content above 12%) was added as nitrogen source (in solution in
      acetone) alongside amino acids or as sole N source. Either starch or carboxy
      methyl cellulose were provided as carbon sources. After 28 days of growth the
      highest decrease of nitrocellulose was observed with Chaetomium elatum when up to
      43% was degraded in a medium containing nitrocellulose as the only nitrogen
      source. Coprinus cinereus caused a 37% decrease of nitrocellulose when provided
      with amino acids and starch as co-substrate. In cultures of Trametes versicolor,
      Pleurotus ostreatus and Trichoderma reesei, only 10%-22% decrease of
      nitrocellulose was measured in all media. In the presence of nitrocellulose with
      N content below 12% supplied as 3 mm pellets as the only carbon source, or with
      nitrocellulose with carboxy-methyl cellulose, the release of nitrite and nitrate
      from liquid cultures of Chaetomium elatum was measured. Between 6 and 9 days of
      growth in these media, an increase in both nitrite and nitrate was observed with
      a loss in weight of nitrocellulose up to 6% achieved after 34 days. The physical
      nature of the NC pellets may have reduced the rate of degradation in comparison
      with supplying NC in solution in the cultures.

PMID- 15865148
TI  - Biodegradation of naphthalene-2-sulfonic acid present in tannery wastewater by
      bacterial isolates Arthrobacter sp. 2AC and Comamonas sp. 4BC.
AB  - Two bacterial strains, 2AC and 4BC, both capable of utilizing naphthalene-2
      sulfonic acid (2-NSA) as a sole source of carbon, were isolated from activated
      sludges previously exposed to tannery wastewater. Enrichments were carried out in
      mineral salt medium (MSM) with 2-NSA as the sole carbon source. 16S rDNA
      sequencing analysis indicated that 2AC is an Arthrobacter sp. and 4BC is a
      Comamonas sp. Within 33 h, both isolates degraded 100% of 2-NSA in MSM and also 2
      NSA in non-sterile tannery wastewater. The yield coefficient was 0.33 g biomass
      dry weight per gram of 2-NSA. A conceptual model, which describes the aerobic
      transformation of organic matter, was used for interpreting the biodegradation
      kinetics of 2-NSA. The half-lives for 2-NSA, at initial concentrations of 100 and
      500 mg/l in MSM, ranged from 20 h (2AC) to 26 h (4BC) with lag-phases of 8 h
      (2AC) and 12 h (4BC). The carbon balance indicates that 75-90% of the initial TOC
      (total organic carbon) was mineralized, 5-20% remained as DOC (dissolved organic
      carbon) and 3-10% was biomass carbon. The principal metabolite of 2-NSA
      biodegradation (in both MSM and tannery wastewater) produced by Comamonas sp. 4BC
      had a MW of 174 and accounted for the residual DOC (7.0-19.0% of the initial TOC
      and 66% of the remaining TOC). Three to ten percent of the initial TOC (33% of
      the remaining TOC) was associated with biomass. The metabolite was not detected
      when Arthrobacter sp. 2AC was used, and a lower residual DOC and biomass carbon
      were recorded. This suggests that the two strains may use different catabolic
      pathways for 2-NSA degradation. The rapid biodegradation of 2-NSA (100 mg/l)
      added to non-sterile tannery wastewater (total 2-NSA, 105 mg/l) when inoculated
      with either Arthrobacter 2AC or Comamonas 4BC showed that both strains were able
      to compete with the indigenous microorganisms and degrade 2-NSA even in the
      presence of alternate carbon sources (DOC in tannery wastewater = 91 mg/l). The
      results provide information useful for the rational design of bioreactors for
      tannery wastewater treatment.

PMID- 15865149
TI  - Propylphenols are metabolites in the anaerobic biodegradation of propylbenzene
      under iron-reducing conditions.
AB  - The metabolism of monoaromatic hydrocarbons by an iron-reducing bacterial
      enrichment culture originating from diesel-contaminated groundwater was examined
      using d7-propylbenzene as a model hydrocarbon. Sequence analysis of the 16S rDNA
      gene showed that the dominant part (10 of 10 clones) of the enrichment culture
      consisted of a bacterium closely related to clones found in benzene-contaminated
      groundwater and to the iron-reducing beta-proteobacterium, Rhodoferax
      ferrireducens (similarity values were 99.5% and 98.3%, respectively). In
      degradation studies conducted over 18 weeks, d7-propylphenols were detected by
      gas chromatography-mass spectrometry (GC/MS) as intra-cellular metabolites
      concomitant with cell growth in the cultures. The amount of propylphenols
      increased during the exponential growth phase, and by the end of this phase 4 x
      10(-14) moles of ferric iron were reduced and 3 x 10(-15) moles propylphenol
      produced for every cell formed. During the stationary growth phase the cell
      density was approximately 10(7) ml(-1), with significantly correlated amounts of
      propylphenols. Succinate derivates of propylbenzene or phenylpropanol previously
      shown to be the initial metabolites in the anaerobic degradation of alkylbenzenes
      could not be identified. This study is the first to report that oxidation of
      propylbenzene to propylphenols can initiate anaerobic propylbenzene degradation
      and that iron-reducing bacteria are responsible for this process. In addition,
      the study shows the importance of taking account of the metabolites adhering to
      solid phases when determining the extent of biodegradation, so as not to
      underestimate the extent of the process.

PMID- 15865150
TI  - Accelerated degradation of N, N'-dibutylurea (DBU) upon repeated application.
AB  - In a recent study on the degradation of N,N'-dibutylurea (DBU), a breakdown
      product of benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazole carbamate], the
      active ingredient in Benlate fungicides, degradation half-lives of 1.4-46.5 days
      were observed across several soils incubated at various combinations of soil
      moisture potential (-0.03 and -0.1 MPa) and temperature (23, 33, and 44 degrees
      C) for a single DBU application of 0.08 and 0.8 microg g(-1) (Lee et al. 2004).
      However, Benlate can be applied as often as every 7 days resulting in the
      repeated application of DBU likely to be present in the Benlate over a growing
      season. In this study, the effect of seven repeated DBU applications on
      mineralization rate was investigated in two soils, which encompass the range in
      rates previously observed. For the slower degrading soil, repeated DBU
      application increased mineralization from 0.029 to 0.99 day(-1) at the 0.08
      microg g(-1) rate, and 0.037 to 0.89 day(-1) at the 0.8 microg g(-1) rate. For
      the faster degrading soil, effects on mineralization of repeated DBU applications
      were small to negligible. For the latter soil, the effect on mineralization of
      applied DBU concentrations from 0.0008 to 80 microg g(-1) was also investigated.
      Mineralization rates decreased from 0.43 to 0.019 day(-1) with increasing DBU
      concentrations. However, the amount of DBU mineralized by day 70 was similar
      across concentrations and averaged 83% of applied. Microbial respiration was not
      affected by increasing DBU concentrations. These findings support the supposition
      that DBU is readily degraded by soil microorganisms, thus unlikely to accumulate
      in agricultural soils.

PMID- 15865151
TI  - 3-chloro-, 2,3- and 3,5-dichlorobenzoate co-metabolism in a 2-chlorobenzoate
      degrading consortium: role of 3,5-dichlorobenzoate as antagonist of 2
      chlorobenzoate degradation. Metabolism and co-metabolism of chlorobenzoates.
AB  - A study was made of the metabolic and co-metabolic intermediates of 2- and 3
      chlorobenzoate, 2,3- and 3,5-dichlorobenzoate to elucidate the mechanism(s)
      involved in the negative effects observed on the growth of a chlorobenzoate
      degrading microbial consortium in the presence of mixed chlorobenzoates. 2
      Chloromuconate accumulated as the end-product in the cultural broths of the
      microbial consortium during growth on 2-chlorobenzoate; the same 2-chloromuconate
      was identified in the reaction mixtures of resting cells pregrown on 2
      chlorobenzoate and exposed to 3-chloro- and 2,3-dichlorobenzoate, while in
      similar experiments 1,2-dihydroxy-3,5-dichloro-cyclohexa-3,5-dienoate was
      detected as dead-end product of 3,5-dichlorobenzoate co-metabolism. These results
      suggest an initial degradative attack by 2-chlorobenzoate induced dioxygenase(s).
      The role of 3,5-dichlorobenzoate as an antagonist of 2-chlorobenzoate degradation
      was also studied: in the presence of mixed 2-chloro- and 3,5-dichlorobenzoate,
      the 3,5-dichlorobenzoate preferential uptake by the resting cells of the
      chlorobenzoate-degrading consortium was observed. 2-Chlorobenzoate entered the
      cells only after the complete removal of the co-substrate. In growing cells
      experiments, the addition of 1,2-dihydroxy-3,5-dichloro-cyclohexa-3,5-dienoate,
      the 3,5-dichlorobenzoate co-metabolite, to 2-chlorobenzoate exerted the same
      antagonistic effect of the parent compound, inhibiting both the microbial growth
      and the degradative process. These data are discussed, allowing us to attribute
      the inhibitory effects observed to a substrate/co-substrate competition, though
      other additional causes may not be totally excluded.

PMID- 15865152
TI  - Reductive dechlorination of hexachlorocyclohexane (HCH) isomers in soil under
      anaerobic conditions.
AB  - The biological anaerobic reductive dechlorination of beta-hexachlorocyclohexane
      under methanogenic conditions was tested in a number of contaminated soil samples
      from two locations in the Netherlands. Soils from a heavily polluted location
      showed rapid dechlorination of beta-hexachlorocyclohexane to benzene and
      chlorobenzene with lactate as electron donor. Soils from an adjacent slightly
      polluted location did not show substantial dechlorination of beta
      hexachlorocyclohexane within 4 months. A heavily polluted sample was selected to
      optimise the dechlorination. All tested hexachlorocyclohexane isomers (alpha-,
      beta-, gamma-, and delta-), either added separately or simultaneously, were
      dechlorinated in this soil sample. The most rapid dechlorination was observed at
      a temperature of 30 degrees C. Dechlorination of beta-hexachlorocyclohexane was
      observed with acetate, propionate, lactate, methanol, H2, yeast extract and
      landfill leachate as electron donors. In a soil percolation column, packed with a
      selected heavily polluted soil sample, the presence of 10 mM sulphate in the
      influent led to simultaneous dechlorination of beta-hexachlorocyclohexane and
      sulphate reduction. When the column was fed with 10 mM nitrate instead of
      sulphate, dechlorination ceased immediately. After omitting nitrate from the
      influent, dechlorination activity recovered in about 1 month. Also in a separate
      column, the addition of nitrate from the start of the experiment did not result
      in dechlorination of beta-HCH. The significance of these experiments for in situ
      bioremediation of polluted soils is discussed.

PMID- 15865153
TI  - Isolation and characterization of phenanthrene-degrading Sphingomonas
      paucimobilis strain ZX4.
AB  - Phenanthrene-degrading bacterium strain ZX4 was isolated from an oil-contaminated
      soil, and identified as Sphingomonas paucimobilis based on 16S rDNA sequence,
      cellular fatty acid composition, mol% G + C and Biolog-GN tests. Besides
      phenanthrene, strain ZX4 could also utilize naphthalene, fluorene and other
      aromatic compounds. The growth on salicylic acid and catechol showed that the
      strain degraded phenanthrene via salicylate pathway, while the assay of catechol
      2,3-dioxygenase revealed catechol could be metabolized through meta-cleavage
      pathway. Three genes, including two of meta-cleavage operon genes and one of GST
      encoding gene were obtained. The order of genes arrangement was similar to S-type
      metapathway operons. The phylogenetic trees based on 16S rDNA sequence and meta
      pathway gene both revealed that strain ZX4 is clustered with strains from genus
      Sphingomonas.

PMID- 15865154
TI  - Effect of temperature and additional carbon sources on phenol degradation by an
      indigenous soil Pseudomonad.
AB  - A new indigenous soil bacterium Pseudomonas sp. growing on phenol and on a
      mixture of phenol, toluene, o-cresol, naphthalene and 1,2,3-trimethylbenzene
      (1,2,3-TMB) was isolated and characterized. Phylogenetic analysis suggested its
      classification to Pseudomonadaceae family and showed 99.8% DNA sequence identity
      to Pseudomonas pseudoalcaligenes species. The isolate was psychrotroph, with
      growth temperatures ranging from ca. 0 to 40 degrees C. The GC-MS structural
      analysis of metabolic products of phenol degradation by this microorganism
      indicated a possible ortho cleavage pathway for high concentrations (over 200 mg
      L(-1)) of phenol. Biodegradation rates by this species were found to be three
      times more effective than those previously reported by other Pseudomonas strains.
      The effect of temperature on phenol degradation was studied in batch cultures at
      temperatures ranging from 10 to 40 degrees C and different initial phenol
      concentrations (up to 500 mg L(-1)). Above 300 mg L(-1) of initial phenol
      concentration no considerable depletion was recorded at both 10 and 40 degrees C.
      Maximum degradation rates for phenol were recorded at 30 degrees C. The
      biodegradation rate of phenol was studied also in the presence of additional
      carbon sources (o-cresol, toluene, naphthalene, 1,2,3-TMB) at the optimum growth
      temperature and was found significantly lower by a factor of eight in respect to
      the strong competitive inhibition between the substrates and the more available
      sources of carbon and energy. The Haldane equation mu = mum S/(Ks + S + S2/K1)
      was found to best fit the experimental data at the optimum temperature of 30
      degrees C than the Monod equation with kinetic constants mum = 0.27 h(-1), KS =
      56.70 mg L(-1), KI = 249.08 mg L(-1).

PMID- 15865155
TI  - Development of an enzymatic assay for the determination of cellulose
      bioavailability in municipal solid waste.
AB  - As there is a constant need to assess the biodegradation potential of refuse
      disposed of in landfills, we have developed a method to evaluate the
      biodegradability of cellulosic compounds (cellulose and hemicellulose) in
      municipal solid waste. This test is based on the quantification of
      monosaccharides released after the hydrolysis of solid waste samples with an
      optimised enzyme preparation containing commercially available cellulases and
      hemicellulases. We show that the amounts of monosaccharides could be related to
      the biodegradability of the cellulosic material contained in the samples. This
      enzymatic cellulose degradation test was assayed on 37 samples originating from
      three Belgian landfills and collected at different depths. As results correlated
      well with those obtained with a classical biochemical methane potential assay,
      this new and rapid test is sufficiently reliable to evaluate cellulose
      bioavailability in waste samples.

PMID- 15865156
TI  - Biodegradation of monochloroacetic acid used as a sole carbon and energy source
      by Xanthobacter autotrophicus GJ10 strain in batch and continuous culture.
AB  - Batch and continuous mode degradation of monochloroacetic acid used as a sole
      carbon and energy source in the concentration range of 0.9-48.4 mM by pure
      culture of Xanthobacter autotrophicus GJ10 was investigated. The substrate was
      completely degraded in each flask in batch system. Partial substrate inhibition
      occurred at the concentrations exceeding 25.4 mM. Temporary accumulation of
      glycolic acid in the medium indicated that dehalogenation was undergoing faster
      than further utilization of glycolate. Three different carbon substrates were
      used for inoculum preparation--1,2-dichloroethane, tri-sodium citrate and a
      nutrient broth. The fastest growth on monochloroacetate occurred for 1,2
      dichloroethane-grown inoculum. The assays of haloacid dehalogenase in crude
      extract indicated that the bacteria grown on 1,2-dichloroethane possessed higher
      level of the enzyme. The response of the GJ10 culture towards spikes of 20 mM
      monochloroacetate was tested in 2.5-1 continuously stirred tank fermentor. The
      substrate was readily utilized within 7-8 h. Continuous degradation of
      monochloroacetate in the fermentor was demonstrated for monochloroacetate
      concentration of 20 mM and dilution rate 0.016 h(-1). Quantitative agreement
      between the amount of monochloroacetate introduced and chloride released was
      found. The results demonstrated that the strain X. autotrophicus GJ10 might be
      suitable for biodegradation of monochloroacetate contaminated media.

PMID- 15865158
TI  - Biodegradation of bisphenol A by cells and cell lysate from Sphingomonas sp.
      strain AO1.
AB  - The capacity and pathway of bisphenol A [BPA; 2,2-bis(4-hydroxyphenyl)propane]
      degradation in Sphingomonas sp. strain AO1, which was isolated from the soil of a
      vegetable-growing field in Japan, were investigated. The bacterial strain was
      able to grow in a basal mineral salt medium containing BPA as the sole carbon
      source (BSMB medium), and was able to degrade 115 microg ml(-1) BPA in 6 h in L
      medium. Several BPA metabolites were detected in the culture supernatant by HPLC
      and then identified by GC-MS and LC-MS-MS. These compounds were confirmed to be
      the same as those reported for other BPA-degrading bacteria. BPA degradation by
      cells in the basal mineral salt medium was induced by BPA, and activity was
      detected only in the intracellular soluble fraction in the presence of coenzymes,
      such as NADH, NAD+, NADPH or NADP+. The addition of metyrapone, a cytochrome P450
      inhibitor, to BSMB medium resulted in a decrease in BPA degradation and cell
      growth. The BPA-degradation activity of the intracellular soluble fraction was
      also inhibited by the cytochrome P450 inhibitor. Carbon monoxide difference
      spectra indicated that cytochrome P450 was present in the cells and that the
      amount of cytochrome P450 corresponded to the cellular BPA-degradation activity.
      Our results provide evidence that the cytochrome P450 system is involved in BPA
      metabolism in Sphingomonas sp. strain AO1.

PMID- 15865157
TI  - Degradation of organic pollutants by methane grown microbial consortia.
AB  - Microbial consortia were enriched from various environmental samples with methane
      as the sole carbon and energy source. Selected consortia that showed a capacity
      for co-oxidation of naphthalene were screened for their ability to degrade methyl
      tert-butyl-ether (MTBE), phthalic acid esters (PAE), benzene, xylene and toluene
      (BTX). MTBE was not removed within 24 h by any of the consortia examined. One
      consortium enriched from activated sludge ("AAE-A2"), degraded PAE, including
      (butyl-benzyl)phthalate (BBP), and di-(butyl)phthalate (DBP). PAE have not
      previously been described as substrates for methanotrophic consortia. The
      apparent Km and Vmax for DBP degradation by AAE-A2 at 20 degrees C was 3.1 +/-
      1.2 mg l(-1) and 8.7 +/- 1.1 mg DBP (g protein x h)(-1), respectively. AAE-A2
      also showed fast degradation of BTX (230 +/- 30 nmol benzene (mg protein x h)(-1)
      at 20 degrees C). Additionally, AAE-A2 degraded benzene continuously for 2 weeks.
      In contrast, a pure culture of the methanotroph Methylosinus trichosporium OB3b
      ceased benzene degradation after only 2 days. Experiments with methane mono
      oxygenase inhibitors or competitive substrates suggested that BTX degradation was
      carried out by methane-oxidizing bacteria in the consortium, whereas the
      degradation of PAE was carried out by non-methanotrophic bacteria co-existing
      with methanotrophs. The composition of the consortium (AAE-A2) based on polar
      lipid fatty acid (PLFA) profiles showed dominance of type II methanotrophs (83
      92% of biomass). Phylogeny based on a 16S-rRNA gene clone library revealed that
      the dominating methanotrophs belonged to Methylosinus/Methylocystis spp. and that
      members of at least 4 different non-methanotrophic genera were present
      (Pseudomonas, Flavobacterium, Janthinobacterium and Rubivivax).

PMID- 15865159
TI  - Metabolites and dead-end products from the microbial oxidation of quaternary
      ammonium alcohols.
AB  - Methyl-triethanol-ammonium originates from the hydrolysis of the parent esterquat
      surfactant, which is used as softener in fabric care. The initial steps of the
      catabolism were investigated in cell-free extracts of the bacterial strain MM 1
      able to grow with methyl-triethanol-ammonium as sole source of carbon, energy and
      nitrogen. The initial degradation of methyl-triethanol-ammonium is an
      enzymatically catalyzed reaction, located in the particulate fraction of strain
      MM 1. The oxygen dependent reaction occurred also in presence of phenazine
      methosulfate as an alternative electron acceptor. As soon as one ethanol group of
      methyl-triethanol-ammonium was oxidized to the aldehyde, cyclic hemiacetals were
      formed by intramolecular cyclization. The third ethanol group of methyl
      triethanol-ammonium was oxidized to the aldehyde and the carboxylic acid
      sequentially. The structurally related compounds dimethyl-diethanol-ammonium and
      choline were oxidized as well, whereas (+/-)-2,3-dihydroxypropyl-trimethyl
      ammonium was not converted at all. The structures of the metabolites were
      established by 1D and 2D 1H, 13C and 14N NMR spectroscopy and by capillary
      electrophoresis mass spectrometry.

PMID- 15865160
TI  - Development of a catabolically significant genetic probe for polycyclic aromatic
      hydrocarbon-degrading mycobacteria in soil.
AB  - A gene probe for the detection of polycyclic aromatic hydrocarbon (PAH) induced
      nidB and nidA dioxygenase genes has been designed from Mycobacteria JLS, KMS, and
      MCS. The probe detects a catabolic gene involved in the initial steps of PAH
      biodegradation in mycobacteria. The gene probe is comprised of three PCR primer
      sets designed to detect the genes that code for two subunits of the PAH induced
      dioxygenase enzyme within PAH-degrading mycobacteria. The probe was built by
      combining three primer sets with a DNA extraction procedure that was designed to
      lyse the gram-positive mycobacteria cells while in the soil matrix and remove PCR
      inhibitors. The probe was tested on PAH contaminated soils undergoing
      bioremediation through landfarming and uncontaminated soils from the same site.
      The PAH gene probe results demonstrate that the dioxygenase genes can be detected
      in soils. Sequencing the nidA and nidB PCR products verified that the genes were
      detected in soil. Comparisons of the sequences obtained from the soil probe to
      seven known nid gene sequences from various PAH-degrading mycobacteria showed
      between 97 and 99% nucleotide matches with the nidB gene and 95 and 99% matches
      with the nidA gene.

PMID- 15865161
TI  - Biochemical and molecular characterisation of the 2,3-dichloro-1-propanol
      dehalogenase and stereospecific haloalkanoic dehalogenases from a versatile
      Agrobacterium sp.
AB  - We previously reported the presence of both haloalcohol and haloalkanoate
      dehalogenase activity in the Agrobacterium sp. strain NHG3. The versatile nature
      of the organism led us to further characterise the genetic basis of these
      dehalogenation activities. Cloning and sequencing of the haloalcohol dehalogenase
      and subsequent analysis suggested that it was part of a highly conserved
      catabolic gene cluster. Characterisation of the haloalkanoate dehalogenase enzyme
      revealed the presence of two stereospecific enzymes with a narrow substrate range
      which acted on D-2-chloropropionic and L-2-chloropropionoic acid, respectively.
      Cloning and sequencing indicated that the two genes were separated by 87 bp of
      non-coding DNA and were preceded by a putative transporter gene 66 bp upstream of
      the D-specific enzyme.

PMID- 15865162
TI  - [Sports and oral health. Introduction].

PMID- 15865163
TI  - [Health care in sports by a team physician, especially in soccer].
AB  - The aim of health care in sports is to promote, to secure, and to recover general
      health of sportsmen, taking into consideration the sport's specific loads. In
      general, a (professional) sports club has a private (para)medical team consisting
      of a team physician, a physiotherapist, and an attendant or masseur. The team
      physician organizes the arrangements and the preventive, diagnostic, and curative
      tasks of the (para)medical team. In sports, sometimes medical emergencies occur,
      such as tongue bite, cardiac problems, hypoglycaemia in diabetes, anaphylactic
      shock, and hypo- as well hyperthermia. Sports injuries are caused by acute
      physical forces, chronic overload or repeated micro-traumas. High-incidence
      injuries in all sports are injuries of joints, bones, head, neck, back and
      abdomen. In case of medical emergencies, the team physician has to take action
      quickly and professionally. If sports injuries occur, the team physician has to
      provide first aid and to arrange a treatment and rehabilitation plan in
      consultation with the paramedical members of the team. During the treatment and
      rehabilitation, the team physician has to be of assistance to sportsmen. In
      arranging some of his tasks, a team physician can ask for assistance or help from
      a dentist or an oral and maxillofacial surgeon.

PMID- 15865164
TI  - [Sports diets and oral health].
AB  - During competition and exercise sessions, (elite) sportsmen may need additional
      carbohydrates, resulting in an increased number of food intakes during the day.
      An increased number of food intakes may induce an increased caries risk.
      Additionally, almost all carbohydrate-containing sportdrinks and sportpowders
      have a high acidity level. Where low body weights are essential for the
      competition, sportsmen are at risk for disordered eating or eating disorders.
      Dentists should be aware of oral health risks of sportsmen and should advise them
      properly.

PMID- 15865165
TI  - [Sports and orofacial injuries].
AB  - Many people enjoy sports, it is healthy and relaxing. There is, however, an
      inherent risk of sustaining injuries and fractures of the maxillofacial skeleton.
      Adequate diagnostics and treatment are mandatory to minimize the possible long
      term consequences of injuries. Dentists may become primary involved in the
      diagnosis of such traumas, particularly when injuries are limited to the
      orofacial region. In addition, they can play an important role in caring for
      sportsmen with orofacial injuries, for instance by endodontic, restorative, and
      prosthodontic treatments. This paper discusses the assessment and treatment of
      fractures of the mandible, the zygoma, the mid-face, the orbital bones, the nose,
      and the frontal sinus. The assessment must followed by treatment as soon as
      possible. Treatment options of orofacial fractures are conservative treatment by
      exercising and/or oral splints and surgical reposition, either or not using
      osteosynthetic materials.

PMID- 15865166
TI  - [Oral conditions in swimmers].
AB  - Swimmers, for several hours a week in contact with pool-water, may develop two
      different types of pool-water related oral conditions: dental erosion and dental
      staining. Dental erosion may occur when the acidity of the pool-water is below a
      pH-value of 5, dental staining when the pH-value of the pool-water is above 6.5.
      Of the two conditions mentioned, dental erosion is the most harmful, because it
      involves an irreversible process. The clinical significance is clarified by a few
      case-reports. In Dutch pools, the pH-value of the pool-water has to be checked
      daily. Therefore, among Dutch swimmers there is only a slight possibility of
      arising oral conditions caused by pool-water.

PMID- 15865167
TI  - High-speed gas chromatography with direct resistively-heated column (ultra fast
      module-GC)-separation measure (S) and other chromatographic parameters under
      different analysis conditions for samples of different complexities and
      volatilities.
AB  - The influence of GC speed on the separation capability of a chromatographic
      system is reported measuring a series of parameters including separation measure
      (S), peak capacity (n), peak width (w), analysis time, t(b) (determined on the
      last eluting compound) and separation measure/analysis time ratio (S/t(b))
      determined by analyzing a bergamot essential oil sample and a standard mixture of
      pesticides. Conventional GC, fast GC (with 10 m (FGC10) and 5 m (FGC5) narrow
      bore columns), and direct resistively-heated ultra fast module-GC (UFM-GC) were
      the GC speed approaches used. The influence of different heating rates with a
      constant flow for FGC5, FGC 10, and UFM-GC and with variable flows for UFM-GC on
      S, n, w, S/t(b), and t(b) was also studied. The results of this study show that:
      (a) separation capability of the chromatographic system (i.e. S and n) and
      analysis time depend on the GC approaches. Within each GC approach, S and n and
      analysis time depend on the heating rates, although to a different extent, and S
      and n decrease much less than the gain in analysis time, in particular when fast
      heating rates are applied; (b) in UFM-GC, the loss of separation capability with
      heating rate can also be partially compensated by the choice of an appropriate
      flow rate that, within each heating rate, may contribute to increase S while
      reducing t(b); (c) within a specific GC approach, the chromatographic system
      (column and stationary phase) and conditions (heating and flow rates) must be
      such to achieve a suitable S-value when two analytes must be separated with a
      given resolution in a minimum analysis time.

PMID- 15865168
TI  - Multidimensional gas chromatography using a double cool-strand interface.
AB  - Commercial interfaces for multidimensional gas chromatography (MDGC) are based
      either on a valve or a pneumatic switching between columns. Both exhibit
      significant drawbacks and only few suppliers exist. An extremely simple interface
      has been set up to overcome these limitations without requiring any pneumatic
      control or valves switching. This new MDGC design is based on the cryo-control of
      the analyte transfer from the first to the second column through two cool strands
      of a capillary. This technique is simple to implement and does not require any
      special column connections. Applications involve non-polar/polar phase
      combinations, as well as chiral analysis, hyphenation to a conventional mass
      spectrometer, and olfactometric detection. In contrast to conventional MDGC
      configuration, the present configuration allows the use of a single oven to
      operate both columns at different temperatures.

PMID- 15865169
TI  - Overloading of the second-dimension column in comprehensive two-dimensional gas
      chromatography.
AB  - Comprehensive two-dimensional gas chromatography (GC x GC) is based on a coupling
      of two GC columns of different characteristics by means of a device that allows
      portions of the effluent from the primary column to be injected onto the second
      dimension column for an additional separation. The time available for the
      separation in the second-dimension column is very short. Thus, this separation
      should be very efficient. The vast majority of GC x GC practitioners use very
      narrow bore columns for the second dimension. While this approach is justified in
      principle, if peaks in the second dimension overload this column, its peak
      capacity is severely reduced. A series of second-dimension columns of varying
      internal diameters, but similar phase ratios, were used to study these effects.
      The results indicate that 250 microm columns often provide comparable second
      dimension peak widths to 100 microm columns, while at the same time being less
      prone to overloading, indicating that they may often be a better choice than
      smaller diameter columns in the second dimension of GC x GC systems.

PMID- 15865170
TI  - Semicontinuous GC analysis and receptor modelling for source apportionment of
      ozone precursor hydrocarbons in Bresso, Milan, 2003.
AB  - The European Ozone Directive 2002/3/EC specifies the analysis of 30 individual C2
      C9 hydrocarbons in urban air with the attribution of emission sources to
      pollution concentrations as a major objective. In the present study, we
      investigate an approach for source apportionment of these ozone precursor
      hydrocarbons in urban air based on reliable semi continuous volatile organic
      compound (VOC) analysis in the field and in vehicle emission laboratory combined
      with multivariate receptor modeling. The GC system relies on an hourly analytical
      cycle based on a trap sample enrichment phase followed by a dual column gas
      chromatographic flame ionisation detector (FID) analysis and has successfully
      been tested during an air monitoring campaign at an urban site (Milan, Italy,
      September 2003) and in the vehicle laboratory performing exhaust emission
      measurements while running driving cycles on a chassis dynamometer (mopeds,
      gasoline and diesel cars). The receptor modeling relies on two complementary
      principles. The chemical mass balance (CMB) modeling apportions well
      characterized source profiles for the 30 individual C2-C9 hydrocarbons in the
      Ozone Directive to the concentrations in ambient air and produces source
      contribution estimates (SCE) as output. The positive matrix factorization (PMF)
      analyses variability in the ambient air concentration data and searches for
      latent variables consisting of co-varying hydrocarbons and produces profiles as
      output, which in this study could be attributed to known emission sources. Both
      CMB and PMF rely on an estimated uncertainty for each input data. A new approach
      is presented, by which the uncertainty is allowed to float as function of the
      photochemical reactivity of the atmosphere and the stability of each individual
      compound.

PMID- 15865171
TI  - Evaluation of a dedicated gas chromatography-mass spectrometry method for the
      analysis of phenols in water.
AB  - The increasing need to routinely analyse phenolic hydrocarbons in aqueous samples
      was addressed by the development and implementation of a state-of-the-art, though
      relatively straightforward, analytical procedure. The proposed method is based on
      acetic anhydride derivatisation of the native phenols, liquid-liquid extraction
      of the corresponding phenyl acetate esters and subsequent analysis by GC-MS. The
      key feature and main strength of the method is located at the injection step
      which applies 'at-once' large volume injection with a programmable temperature
      vaporizer (PTV)-type injector. In the proposed method, the sensitivity gain
      inherent to the higher injection volume was used entirely to proportionally
      miniaturize, considerably accelerate and effectively simplify the otherwise
      tedious and time-consuming derivatisation/extraction step. Method performance, as
      expressed in terms of repeatability, reproducibility, linearity and accuracy, was
      found to be excellent. R.S.D. values, determined in the framework of an extensive
      reproducibility study, ranged between 1.47 and 9.02%. Detection limits were in
      the low ng/L range for all compounds with linear ranges extending up to two
      orders of magnitude. Method accuracy was determined by analyzing a certified
      reference material (PH- 1JM), spiked water samples and participating in a series
      of round robin tests and did not reveal any significant bias for the different
      compounds under investigation.

PMID- 15865172
TI  - Orthogonality considerations in comprehensive two-dimensional gas chromatography.
AB  - This study explores separation orthogonality with respect to comprehensive two
      dimensional gas chromatography (GC x GC) for a range of different column
      polarities in the first dimension (1D), with two second dimension (2D) column
      types. Systematic variation in the net polarity of the first dimension allows the
      effect of column phase relative polarity on analyte retention in both the first
      and second dimensions to be evaluated. First dimension polarity manipulation
      significantly affects elution temperature (T(e)) of the analytes. This alters the
      magnitude of retention on the second dimension, and the extent of utility of
      separation space. By use of retention factor/temperature data in single column
      experiments, along with 1D T(e) data, retention on the 2D column can be
      estimated. This allows the two-dimensional separation to be predicted, and
      compared with experimental data. Predicted GC x GC peak positions corresponded
      favourably with the experimentally derived chromatograms, yielding a simple
      approach for predicting two-dimensional separations, using unique column set
      combinations.

PMID- 15865173
TI  - Increasing the accuracy of determination of nc/nH ratios by gas chromatography
      atomic emission detection.
AB  - The influence of oxygen content in helium on the accuracy of nc/nH ratio
      determination for model mixtures of aliphatic and polyaromatic hydrocarbons and
      polychlorinated biphenyls was studied. The best accuracy was achieved at the
      oxygen content ca. 9%, which was the maximal possible oxygen content in helium
      for this GC-atomic emission detection (helium flow rate was 25 ml min(-1)). Using
      the maximal oxygen flow in plasma the nC/nH ratio determination accuracy
      improvement was accompanied by 10-fold increase in detection limit.

PMID- 15865174
TI  - On the capillary gas chromatographic separation of enantiomers of N
      trifluoroacetyl-O-alkyl esters of selected amino acids on 2,3-di-O-pentyl-6-O
      acyl cyclodextrins.
AB  - In this work, the separation of enantiomers of N-TFA-O-alkyl amino acids on the
      2,3-di-O-pentyl-6-O-acyl alpha-, beta- and gamma-cyclodextrin stationary phases
      has been studied. The influence of structure differences in the alkyl
      substituents bonded to the stereogenic carbon atom (R1), as well as in the ester
      group (R2) of the selected amino acid derivatives, and the selectivity of
      modified alpha-, beta- and gamma-cyclodextrin phases in gas chromatographic
      separation of derivatized amino acid enantiomers was studied in detail. A model
      set of N-TFA-alkyl esters of four amino acids was separated on five columns. The
      separation of enantiomers was evaluated in terms of the interactions of the alkyl
      substituents bonded to the stereogenic carbon (R1) and/or the ester group (R2) of
      the N-TFA-O-alkyl amino acid derivatives as well as the nature of the 3-O-acyl
      group in the 2,6-di-O-pentyl-3-O-acyl alpha-, beta- and gamma-cyclodextrins. It
      was shown that the variation in the enantiomeric separation with temperature and
      the retention order of enantiomers on a given cyclodextrin capillary column
      depends both on the nature of the bonded R1 and R2 alkyl groups. It was found
      that the temperature dependencies of selectivity factors, ln alpha on 1/T, were
      mostly non-linear. The thermodynamic data [delta(deltaS) and [delta(deltaH)]
      which characterize the chiral recognition were used to gain more insight into the
      mechanistic aspects of enantio separation of the N-TFA-O-alkyl amino acid
      derivatives on 2,6-di-O-pentyl-3-O-acyl-alpha-, beta- and gamma-cyclodextrins.

PMID- 15865175
TI  - Residue analysis of organophosphorus pesticides in animal matrices by dual column
      capillary gas chromatography with nitrogen-phosphorus detection.
AB  - Organophosphorus pesticides (OPPs) were determined in matrices of animal origin
      by dual column capillary gas chromatography using nitrogen-phosphorus detection
      (NPD). This method was tested on cow milk and on liver and muscle of wild boar.
      The isolation of these pesticides was performed by liquid partition followed by
      cleanup with solid phase cartridge (SPE C18), after extraction from the matrix.
      The analytes identification was obtained by comparing the retention times in two
      columns with different polarity. The quantification of each OPP was obtained
      using parathion-ethyl as internal standard. The method was developed in a UNI EN
      ISO 9001:2000 certified laboratory. The recovery, investigated by analyzing
      samples spiked at 5, 10 and 50 ppb, ranged from 59 to 117% in milk, from 60 to
      81% in liver and from 68 to 76% in muscle. The limit of quantification (LOQ) and
      limit of detection (LOD) were, respectively, 5 and 1 ppb for each compound and
      allowed quantifying the residues below the legal limits.

PMID- 15865176
TI  - Analysis of chlorinated, sulfochlorinated and sulfonamide derivatives of n
      tetradecane by gas chromatography/mass spectrometry.
AB  - The photosulfochlorination of n-tetradecane by sulfuryl chloride leads to a
      reaction mixture containing unreacted n-tetradecane, chloro n-tetradecanes and n
      tetradecanesulfonyl chlorides. Direct and simultaneous GC analysis of the mixture
      of the sulfochlorinated and chlorinated isomers is followed by mass spectrometry
      identification of all the components either by electron impact (EI-MS) and by
      negative and positive chemical ionisation (NCI-MS and PCI-MS). With the goal of
      performing an accurate quantitative GC analysis, and as n-tetradecanesulfonyl
      chlorides prone to degrade partially into the corresponding chlorides, the former
      are converted to N,N-diethylsufonamides, more stable thermally, and then analysed
      by GC/EI-MS and GC/PCI-MS. The chloro n-tetradecanes, sulfonylchlorides and
      sulfonamides spectra present strong similarities. However, some differences
      between terminal and internal isomers are noticed and the peculiar behaviour of
      sulfonamides is emphasized.

PMID- 15865177
TI  - High-speed capillary gas chromatography for determination of inhalation
      anesthetics.
AB  - To increase sample throughput for GC analysis of inhalation anaesthetics without
      affecting the separation of nitrous oxide (N2O) and halogenated anaesthetics
      (sevoflurane, isoflurane and halothane), we explored the effectiveness of a
      tailor-shortened (12 m) PlotQ capillary column and developed a high-speed version
      of a previously reported GC technique (involving chromatographic separation of
      analytes using a GC-MS system, coupled with a selected ion monitoring (SIM)
      method to increase sensitivity). Efficient separation and repeatable results were
      achieved at a reduced runtime of approximately 7 min (versus 18 min with the
      original method) at a carrier gas flow of 1.5 ml/min. This approach should more
      than double the previous throughput.

PMID- 15865178
TI  - Investigation of photodegradation products generated after UV-irradiation of five
      polybrominated diphenyl ethers using photo solid-phase microextraction.
AB  - In this study, the photoinduced degradation of five polybrominated diphenyl
      ethers (PBDEs), BDE-47, BDE-100, BDE-99, BDE-154 and BDE-153, is studied using
      solid-phase microextraction polydimethylsiloxane fibers as photolytic support.
      PBDEs are extracted from aqueous solutions using SPME fibers that are
      subsequently exposed to UV irradiation for different times (from 2 to 60 min).
      Photodegradation kinetics of the five PBDEs, tentative identification and
      photochemical behavior of the generated photoproducts, as well as
      photodegradation pathways, have been studied employing this on-fiber approach
      technique (photo-SPME) followed by gas chromatography-mass spectrometry analysis.
      Aqueous photodegradation studies have also been performed and compared with photo
      SPME. All the photoproducts detected in the aqueous experiments were previously
      found in the photo-SPME experiments. In this study, reductive debromination by
      successive losses of bromine atoms is confirmed as the main photodegradation
      pathway of PBDEs. A large number of PBDEs were obtained as photoproducts of the
      five target analytes. Other mechanism of photodegradation observed was
      intramolecular cyclization from the homolytic dissociation of the C-Br bond;
      thus, polybromo-dibenzofurans were generated. This work contributes to the study
      of the photodegradation of PBDEs and shows the potential of photo-SPME to
      evaluate the photo-transformation of organic pollutants.

PMID- 15865179
TI  - Multi-residue screening of chlorinated and brominated compounds from aquaculture
      samples using matrix solid-phase dispersion--gas chromatography-mass
      spectrometry.
AB  - An effective multiresidual method for the trace analysis of fifteen compounds
      from a diverse group of pesticides, polybrominated diphenyl ethers (PBDEs),
      polychlorinated biphenyl (PCBs) and polybrominated biphenyl (PBBs) in aquaculture
      feed is described. The analytical procedure is based on the matrix solid-phase
      dispersion (MSPD) of feed sample and subsequent elution with hexane. The MSPD
      process was evaluated using an asymmetrical experimental design 2(3)3(2)//9.
      Factors such as C18 sorbent amount, kind of adsorbents, solvent volume and
      elution mode were considered. The results suggest that the operational MSPD
      conditions are elution with pressure, 1 g of C18, basic alumina as adsorbent and
      30 mL of hexane. The overall method including MSPD procedure and GC coupled to
      mass spectrometry (MS/MS) has been applied to several samples of aquaculture feed
      and marine species. Precision and accuracy of the analytical method were
      determined using the reference material from the International Atomic Energy
      Agency (IAEA-406), showing a good agreement to the referenced values.

PMID- 15865180
TI  - Characterization of non-discriminating tetramethylammonium hydroxide-induced
      thermochemolysis-capillary gas chromatography-mass spectrometry as a method for
      profiling fatty acids in bacterial biomasses.
AB  - Thermochemolysis using tetramethylammonium hydroxide (TMAH) as a method for
      profiling fatty acids (FAs) as methyl esters (FAMEs) was studied with respect to
      discrimination of bacterial fatty acid patterns in Gram-negative Pseudomonas
      putida in comparison with patterns obtained by classical preparation schemes
      (pressurized solvent extraction, alkaline saponification). A new, non
      discriminating pyrolysis approach was used in these experiments. In this method,
      pyrolysis is carried out inside a deactivated stainless steel capillary
      constituting a part of the column train. This approach made it possible to
      distinguish analyte discrimination brought about by (i) the pyrolyzer set-up in
      conventional pyrolysis and (ii) chemical thermochemolysis reaction itself. Our
      results showed no significant discrimination for saturated, monounsaturated and
      cyclopropane FAs when using thermochemolysis temperatures up to 550 degrees C
      with the non-discriminating, capacitive-discharged based approach. Likewise, the
      cis/trans ratio of monounsaturated FAs was preserved. This is in sharp contrast
      to conventional pyrolysis systems (both Curie-point or flash pyrolyzers) using
      much longer thermochemolysis times. When using these systems, artificial
      monounsaturated FAMEs were formed during heat treatment resulting in biased
      species identification/classification. Hydroxy-FAs, chiefly bound covalently in
      lipopolysaccharides, could be almost quantitatively liberated by TMAH using non
      discriminating pyrolysis (beyond 90%), whereas the recoveries were lower with
      conventional approaches. The new method makes it possible to profile fatty acids
      in very small amounts of both solid and liquid samples without significant sample
      preparation. This was exemplified by the results of TMAH-thermochemolysis of a
      fermentation broth taken from an in situ bioremediation reactor to monitor
      enhanced natural attenuation processes, and tomato roots which were subjected to
      cellulolytic bacteria attacks (Streptomyces), resulting in adsorption of these
      carboxymethyl-cellulose decomposing bacteria onto the root.

PMID- 15865181
TI  - Impact of phase ratio, polydimethylsiloxane volume and size, and sampling
      temperature and time on headspace sorptive extraction recovery of some volatile
      compounds in the essential oil field.
AB  - This study evaluates concentration capability of headspace sorptive extraction
      (HSSE) and the influence of sampling conditions on HSSE recovery of an analyte. A
      standard mixture in water of six high-to-medium volatility analytes (isobutyl
      methyl ketone, 3-hexanol, isoamyl acetate, 1,8-cineole, linalool and carvone) was
      used to sample the headspace by HSSE with stir bars coated with different
      polydimethylsiloxane (PDMS) volumes (20, 40, 55 and 110 microL, respectively),
      headspace vial volumes (8, 21.2, 40, 250 and 1000 mL), sampling temperatures (25,
      50 and 75 degrees C) and sampling times (30, 60 and 120 min, and 4, 8 and 16 h).
      The concentration factors (CFs) of HSSE versus static headspace (S-HS) were also
      determined. Analytes sampled by the PDMS stir bars were recovered by thermal
      desorption (TDS) and analysed by capillary GC-MS. This study demonstrates how
      analyte recovery depends on its physico-chemical characteristics and affinity for
      PDMS (octanol-water partition coefficients), sampling temperatures (50 degrees C)
      and times (60 min), the volumes of headspace (40 mL) and of PDMS (in particular,
      for high volatility analytes). HSSE is also shown to be very effective for trace
      analysis. The HSSE CFs calculated versus S-HS with a 1000 mL headspace volumes at
      25 degrees C during 4 h sampling ranged between 10(3) and 10(4) times for all
      analytes investigated while the limits of quantitation determined under the same
      conditions were in the nmol/L range.

PMID- 15865182
TI  - Development of headspace solid-phase microextraction-gas chromatography method
      for the determination of solvent residues in edible oils and pharmaceuticals.
AB  - The application of headspace solid-phase microextraction for isolation and
      enrichment of solvent residues from oils and pharmaceuticals is discussed. The
      optimal parameters for isolation and preconcentration of common process solvents
      (hexane, benzene, toluene and selected chloroderivatives of hydrocarbons) were
      established. Four fiber types (100 microm polydimethylsiloxane (PDMS), 75 microm
      Carboxen-PDMS, 65 microm PDMS-divinylbenzene and 85 microm polyacrylate) were
      evaluated to choose the most efficient coating, able to absorb the greatest
      amount of analytes. GC-flame ionization detection (FID) and GC-electron-capture
      detection systems were used for quantitative and qualitative analysis, adequately
      to the appropriate group of the analytes. For all compounds the limit of
      detection (LOD), linearity, dynamic range, repeatability and intermediate
      precision were estimated.

PMID- 15865183
TI  - Determination of bromophenols as dioxin precursors in combustion gases of fire
      retarded extruded polystyrene by sorptive sampling-capillary gas chromatography
      mass spectrometry.
AB  - Extruded polystyrene (XPS) is often treated with hexabromocyclododecane (HBCD) as
      fire retardant (FR). Because of its aliphatic structure, HBCD is not suspected to
      cause formation of polybrominated dioxins upon combustion. Precursors of
      polybrominated dioxins, namely bromophenols, were detected during tubular furnace
      combustion experiments of FR-XPS in combination with sorptive enrichment on
      polydimethylsiloxane followed by on-line thermal desorption-capillary GC/MS. The
      highest concentration of mono- and tribromophenols detected were 85.9 and 3.7 mg
      kg(-1), respectively, at a temperature of 700 degrees C, while a temperature of
      500 degrees C yielded the highest concentration of dibromophenols namely 10.4 mg
      kg(-1). At a combustion temperature of 900 degrees C no bromophenols were
      detected.

PMID- 15865184
TI  - Simultaneous determination of unmodified sevoflurane and of its metabolite
      hexafluoroisopropanol in urine by headspace sorptive extraction-thermal
      desorption-capillary gas chromatography-mass spectrometry.
AB  - Unmodified sevoflurane and its metabolite, hexafluoroisopropanol (HFIP), have
      both been proposed as biomarkers of exposure in post-shift urine for operating
      room personnel exposed to inhalation anaesthetic sevoflurane. We used headspace
      sorptive extraction (HSSE) and thermal desorption-capillary GC-MS to assess
      sensitively both compounds in the urine matrix (after a HFIP deconjugation step).
      In GC-MS splitless mode, calibration plots (approximately 15-650 microg/L) were
      linear (r2 > 0.9910) and the limits of detection (1 microg/L for both biomarkers)
      showed increased sensitivity for HFIP with respect to the previously described
      headspace GC-MS method. The method was suitable for biological monitoring of both
      biomarkers of exposure to sevoflurane.

PMID- 15865185
TI  - A rapid method of diagnosing pulmonary tuberculosis using stir bar sorptive
      extraction-thermal desorption-gas chromatography-mass spectrometry.
AB  - A fast method for detection of tuberculostearic acid (TBSA) in sputum samples is
      described. The samples, obtained from patients with known or suspected pulmonary
      tuberculosis, were decontaminated and concentrated before being analyzed by stir
      bar sorptive extraction-thermal desorption-gas chromatography-mass spectrometry
      (SBSE-TD-GC-MS). Prior to extraction, the mycobacterial lipids were hydrolyzed
      and then derivatized with ethyl chloroformate to increase the sorption of the
      compounds by the polydimethylsiloxane (PDMS) stir bar coating. The limit of
      detection (LOD) is 0.2 ng ml(-1). Four sputum samples that were classified by
      direct microscopy as smear-positive or negative were analyzed by GC-MS. TBSA was
      detected at concentrations ranging from 0.47 to 2.3 ng ml(-1). The method is
      sufficiently sensitive to detect TBSA directly in clinical samples without the
      need to culture the organisms.

PMID- 15865186
TI  - Impurity analysis of 1,4-dioxane in nonionic surfactants and cosmetics using
      headspace solid-phase microextraction coupled with gas chromatography and gas
      chromatography-mass spectrometry.
AB  - 1,4-Dioxane impurity in nonionic surfactants and cosmetics were analyzed using
      solid-phase microextraction (SPME) coupled with gas chromatography (GC) and gas
      chromatography-mass spectrometry (GC-MS). Experimental results show that there is
      no significant difference using SPME-GC and SPME-GC-MS for analysis of 1,4
      dioxane in three types of nonionic surfactants at the 95% confidence level. The
      relative standard deviation (R.S.D.) values of each analytical method were
      smaller than 3%. The amount of 1,4-dioxane was found to vary from 11.6 +/- 0.3
      ppm to 73.5 +/- 0.5 ppm in 30% of nonionic surfactants from manufacturers in
      Taiwan. These methods were linear over the studied range of 3-150 ppm with
      correlation coefficients higher than 0.995. The recoveries of 1,4-dioxane for
      these nonionic surfactants following SPME were all higher than 96 +/- 1% (n = 3).
      The detection limits of 1,4-dioxane for these nonionic surfactants following SPME
      were from 0.06 ppm to 0.51 ppm. The experimentally determined level of 1,4
      dioxane in cosmetics from manufacturers in Taiwan varied from 4.2 +/- 0.1 ppm to
      41.1 +/- 0.6 ppm in 22% of daily used cosmetics following SPME coupled with GC
      and GC-MS. Conventional solvent extraction takes around 1 h for extraction and
      reconcentration but SPME takes only around 10 min. SPME provides better analyses
      of 1,4-dioxane in nonionic surfactants and cosmetics than conventional solvent
      extraction and head space pretreatments in term of simplicity, speed, precision,
      detection limit, and solvent consumption.

PMID- 15865187
TI  - Determination of low-molecular mass aldehydes by automated headspace solid-phase
      microextraction with in-fibre derivatisation.
AB  - Headspace solid-phase microextraction (HS-SPME) analysis of low-molecular mass
      (C1-C10) aldehydes in aqueous solutions was investigated, using
      pentafluorophenylhydrazine (PFPH) and o-2,3,4,5,6
      (pentafluorobenzyl)hydroxylamine hydrochloride (PFBHA) as in-fibre derivatisation
      reagents. Analysis of the derivatives was achieved, using GC-flame ionisation
      detection (FID). A comparison of the two reagents showed that PFBHA was superior
      to PFPH under the investigated conditions. Fundamental studies of the PFBHA and
      PFPH reactions showed that the kinetics of the process was limited by the mass
      transport rate of the analytes to the fibre. The developed PFBHA method gave
      detection limits in the low to sub-microgram per litre range for most of the
      aldehydes tested. The method was applied successfully to the analysis of
      particleboard, wine and fish samples.

PMID- 15865188
TI  - Optimized method for the determination of 25 polychlorinated biphenyls in water
      samples using stir bar sorptive extraction followed by thermodesorption-gas
      chromatography/mass spectrometry.
AB  - An optimized method using stir bar sorptive extraction (SBSE) for the
      determination of 25 polychlorinated biphenyls (PCBs) from water samples among
      them three of the most toxic coplanar PCBs (PCB 77, PCB 126 and PCB 169) was
      developed. Since the investigated PCBs comprise all steps of chlorination (from
      PCB 1 as monochlorobiphenyl to PCB 209 as decachlorobiphenyl) the results should
      be representative for the total class of the 209 PCB congeners. For 8 ml spiked
      water samples with 2 ml methanol addition and 2 h exposure time of stir bars
      recoveries between 28% (PCB 209) and 93% (PCB 1, PCB 52, PCB 77) were found.
      Detection limits between 0.05 ng/l and 0.15 ng/l were calculated for the
      combination of SBSE and thermodesorption-GC/MS. The procedure was applied to the
      investigation of groundwater and river water samples from the industrial region
      of Bitterfeld northern Leipzig, Germany.

PMID- 15865189
TI  - Determination of phenols in lake and ground water samples by stir bar sorptive
      extraction-thermal desorption-gas chromatography-mass spectrometry.
AB  - A simple and inexpensive method for sorptive extraction of phenols from water
      samples is presented. A polydimethyl siloxane (PDMS) stir bar (Twister) is used
      as an extraction medium for derivatized phenols, which is thermally desorbed and
      analyzed by gas chromatography-mass spectrometry (GC-MS). Its performance was
      illustrated and evaluated for the enrichment of microg l(-1) to ng l(-1) of
      phenol and selected chlorophenols in water samples. The method showed good
      linearity, recoveries and blank levels, as well as advantages such as
      sensitivity, simplicity, low cost and high feasibility, being successfully
      applied for the analysis of phenolic compounds in natural water samples.

PMID- 15865190
TI  - Non-particulate (continuous bed or monolithic) acrylate-based capillary columns
      for reversed-phase liquid chromatography and electrochromatography.
AB  - Three approaches are described to synthesize acrylic non-particulate beds (also
      called continuous beds or monoliths) in aqueous polymerization media for reversed
      phase capillary liquid chromatography/electrochromatography. In the first, hexyl
      acrylate comonomer was dissolved together with water soluble polar comonomers
      using a non-ionic detergent. In the second, a new alkyl ammonium salt comonomer,
      (3-allylamino-2-hydroxypropyl)dodecyldimethylammonium chloride was used, which is
      water soluble and has detergent properties itself. The alkyl group of this
      comonomer provides hydrophobicity while the ionic groups generate electroosmosis
      in the non-particulate bed. In the third approach, the alkyl comonomer was used
      as a detergent to dissolve another hydrophobic comonomer in an aqueous
      polymerization medium. All three approaches were evaluated with respect to
      hydrophobicity, efficiency and electroosmotic properties of the beds.
      Hydrophobicity expressed as methylene group selectivity for the three types of
      the beds in 50% methanol mobile phase was 1.86, 1.16 and 1.78, electroosmotic
      mobility -5.14 x 10(-5), 6.89 x 10(-5) and 6.37 x 10(-5) cm2 V(-1) s(-1) and
      efficiency for the retained compound (methylparabene) 67,000, 93,000 and 110,000
      plates m(-1) correspondingly. The columns were tested using pressure driven
      capillary chromatography and capillary electrochromatography. The influence of
      polymerization temperature on hydrodynamic permeability, separation impedance and
      inverse size exclusion porosimetry characteristics were used to evaluate the
      separation columns. The increase of the polymerization temperature resulted
      higher permeability of the bed, separation impedance and lower polymeric skeleton
      porosity. Further characterisation was provided by examining the separation
      efficiency observed for a series of benzoic acid esters and alkyl parabens.

PMID- 15865191
TI  - Online preconcentration of thyrotropin-releasing hormone (TRH) by SDS-modified
      reversed phase column for microbore and capillary high-performance liquid
      chromatography (HPLC).
AB  - Thyrotropin-releasing hormone (TRH, pGlu-His-Pro-amide) is an important
      tripeptide existing in biological systems at low concentrations. It is a fairly
      hydrophilic peptide, cationic in acidic solutions. Preconcentration online before
      reversed phase chromatography separation can enhance concentration detection
      limits of hydrophobic, but not hydrophilic species. The hydrophilic TRH can be
      preconcentrated using a reversed phase precolumn charged with sodium dodecyl
      sulfate (SDS). The separation also uses SDS. The preconcentration is effective
      for a microbore system, achieving detection limit of 250 pM for a sample size of
      500 microl with electrochemical detection of the biuret complex formed post
      column. Preconcentration using an online precolumn is also effective in packed
      capillary high-performance liquid chromatography (HPLC) with a detection limit of
      3 nM in 24 microl.

PMID- 15865192
TI  - Determination of phospholipids in dairy products by SPE/HPLC/ELSD.
AB  - The aim of this work was to evaluate the performance of different methods for
      both milk lipid extraction and phospholipids separation. As far as the lipid
      extraction procedure is concerned, the Folch method showed a higher phospholipid
      recovery with respect to the Rose-Gottlieb method. Different SPE cartridges and
      solvent phases were tested to carry out the separation of phospholipids from fat.
      The yield of extraction was evaluated by isolating phospholipids from both milk
      fat and synthetic fat; Standard Addition Method was applied as well. The
      isolation of the phospholipids by SPE silica column and subsequent analysis by
      HPLC/ELSD was shown to be an accurate and reproducible analytical method for the
      determination of phosphatidylethanolamine, phosphatidylinositol,
      phosphatidylserine, phosphatidylcholine and sphingomyelin in milk fat extracted
      by Folch method.

PMID- 15865193
TI  - Identification of the major selenium compound, Se-Methionine, in three yeast
      (Saccharomyces cerevisiae) dietary supplements by on-line narrowbore liquid
      chromatography-electrospray tandem mass spectrometry.
AB  - On-line monitoring of six Se-compounds was accomplished by using an XTerra MS C18
      column coupled to electrospray tandem mass spectrometry (ES-MS-MS). In view of
      the nature of the compounds, the positively charged ion pairing agent
      tetraethylammoniumchloride (TEACl) was added to the mobile phase. The HPLC-ES-MS
      MS method was optimized with six commercially available Se-compounds.
      Substitution of the analytical column by the narrowbore type significantly
      enhanced the sensitivity of the method. We were able to detect the m/z of these
      six molecules on-line. Furthermore, all product ions could be monitored. The
      method was applied to three different yeast-based supplements. They were
      submitted to proteolytic digestion and screened for their Se-content by HPLC-HG
      AFS (hydride generation-atomic fluorescence spectrometry). By application of on
      line narrowbore HPLC-electrospray tandem mass spectrometry, the main compound
      present in these three supplements, Se-Methionine, could be measured on its m/z
      and its product ions. The method can be further extended for on-line measurement
      of different Se-species in complex matrices

PMID- 15865194
TI  - Evaluation of capillary electrophoresis for determining the concentration of
      dissolved silica in geothermal brines.
AB  - The determination of silica concentrations in geothermal brines is widely
      recognized as a difficult analytical task due to its complex chemical
      polymerization kinetics that occurs during sample collection and chemical
      analysis. Capillary electrophoresis (CE) has been evaluated as a new reliable
      analytical method to measure silica (as silicates) in geothermal brines.
      Synthetic and geothermal brine samples were used to evaluate CE methodology. A
      capillary electrophoresis instrument, Quanta 4000 (Waters-Millipore) coupled with
      a Waters 820 workstation was used to carry out the experimental work. The
      separation of silicates was completed in approximately 5.5 min using a
      conventional fused-silica capillary (75 microm i.d. x 375 microm o.d. x 60 cm
      total length). A hydrostatic injection (10 cm for 20 s at 25 degrees C) was
      employed for introducing the samples. The carrier electrolyte consisted of 10 mM
      sodium chromate, 3 mM tetradecyltrimethyl-ammonium hydroxide (TTAOH), 2 mM sodium
      carbonate, and 1 mM sodium hydroxide, adjusted to a pH 11.0 +/- 0.1. Silicates
      were determined using an indirect UV detection at a wavelength of 254 nm with a
      mercury lamp and with a negative power supply (-15 kV). A good reproducibility in
      the migration times (%R.S.D. approximately 1.6%) based on six non-consecutive
      injections of synthetic brine solutions was obtained. A linear response between
      silica concentration and corrected peak area was observed. Ordinary (OLR) and
      weighted (WLR) linear regression models were used for calculating silica
      concentrations in all samples using the corresponding fitted calibration curves.
      The analytical results of CE were finally compared with the most probable values
      of synthetic reference standards of silica using the Student's t-test. No
      significant differences were found between them at P = 0.01. Similarly, the
      atomic absorption spectrometry (AAS) results were also compared with the most
      probable concentrations of the same reference standards, finding significant
      differences at P = 0.01.

PMID- 15865195
TI  - Analysis of tetrabromobisphenol A and other phenolic compounds in water samples
      by non-aqueous capillary electrophoresis coupled to photodiode array ultraviolet
      detection.
AB  - Non-aqueous capillary electrophoresis (NACE) with large-volume sample stacking
      injection using the electroosmotic flow pump (LVSEP) has been developed for the
      determination of tetrabromobisphenol A (TBBPA) and other phenolic compounds in
      environmental matrices. Methanol has been used as run buffer solvent to reduce
      the electroosmotic flow (EOF). Identification and quantification of the analytes
      was performed by photodiode array ultraviolet detection. LVSEP-NACE improved
      sensitivity of the peak height by 90-300-fold. The method developed was applied
      to the analysis of TBBPA in river water and wastewater samples, using solid-phase
      extraction (SPE) as sample pretreatment process. The average recoveries of the
      analytes were in the range of 96-106% and 73-103% for 1 L of river water and 0.5
      L of wastewater samples, respectively. When the method was based on off line SPE
      LVSEP-NACE, sensitivity was improved by 3300-4500-fold and 1600-2200-fold for
      river water and wastewater samples, respectively.

PMID- 15865196
TI  - Integrated microfabricated systems including a purification module and an on-chip
      nano electrospray ionization interface for biological analysis.
AB  - We report here on an integrated microfabricated device dedicated to the
      preparation of biological samples prior to their on-line analysis by electrospray
      ionization-mass spectrometry (ESI-MS). This microfluidic device is fabricated
      using the negative photoresist SU-8 by microtechnology techniques. The device
      includes a chromatographic module plus an ESI interface for MS. The
      chromatographic module is dedicated to sample purification and is based on a
      polymer monolithic phase which includes hydrophobic moieties. The ESI interface
      is integrated onto the chip and is based on a capillary slot. We present here the
      integration of these different modules onto a single system that is fabricated
      via a SU-8-based microtechnology route. We present also their testing for the
      purification of peptide samples. This started with a partial integration step
      with the combination of at least two of the modules (microsystem + monolith;
      microsystem + nib) and their test before the fabrication and testing of fully
      integrated microsystems.

PMID- 15865197
TI  - Rapid separation of antimicrobial metabolites by microchip electrophoresis with
      UV linear imaging detection.
AB  - This research examines microchip electrophoresis with linear imaging UV detection
      for the analysis of antimicrobial metabolites, monoacetylphloroglucinol (MAPG)
      and 2,4-diacetylphloroglucinol (2,4-DAPG) from Pseudomonas fluorescens F113.
      Initial results show the separation of MAPG, 2,4-DAPG and resorcinol in less than
      20 s. This was achieved using a quartz microchip with a separation channel length
      of 25 mm. In order to quantitate the amount of MAPG and 2,4-DAPG in a microbial
      cultured supernatant sample, on-chip sample introduction in a methanol/buffer
      matrix was investigated. Sample introduction/injection parameters were optimized
      to improve sensitivity and thus decrease the limit of detection (LOD). The amount
      of antimicrobial metabolites present was quantitated with a separation time of 15
      s. A previously developed capillary electrophoretic method was compared to the
      microchip method in relation to speed, efficiency, precision, linear range and
      limit of detection. This investigation shows the fastest separation so far of
      these antimicrobial metabolites with high efficiency.

PMID- 15865198
TI  - Novel system for classifying chromatographic applications, exemplified by
      comprehensive two-dimensional gas chromatography and multivariate analysis.
AB  - For practical chromatographers it is extremely difficult to judge the merits and
      limitations of new technological developments. On the other hand, it is nearly
      impossible for those at the forefront of technology to judge the implications of
      their efforts for all specific applications of chromatography. Both
      chromatographers and researchers can be aided by a classification of the numerous
      specific applications into a few well-defined categories. In this paper, we
      propose such a classification of all chemical analysis by chromatography into
      three generic types of applications, viz. target-compound analysis, group-type
      separation, and fingerprinting. The requirements for each type are discussed in
      general terms. The classification scheme is applied to assess the benefits and
      limitations of comprehensive two-dimensional gas chromatography (GC x GC) and the
      possible additional benefits of using multivariate-analysis (MVA) techniques for
      each type of application. The conclusions pertaining to the generic types of
      applications are indicative for the implications of new developments for specific
      chemical analysis by chromatography.

PMID- 15865199
TI  - A new mathematical procedure to evaluate peaks in complex chromatograms.
AB  - Automatic peak evaluation in chromatograms and subsequent quantification of
      compound concentrations is still a challenge in the analysis of complex samples
      containing hundreds or thousands of compounds. Although a number of software
      packages for peak evaluation exist, baseline definition and overlapping peaks of
      different shapes are the main reasons which prevent reliable automatic analysis
      of complex chromatograms. A new mathematical procedure is presented which uses
      peak shapes extracted from the chromatogram itself and modified by nonlinear (in
      fact, hyperbolic) stretching of the peak head and tail. With this approach, the
      peak parameters are position, height, scale of front, scale of tail, and
      smoothness of transition from front to tail scaling. This approach is found to
      give a substantially better fit than traditional analytically defined peak
      shapes. Together with a good peak finding heuristic and nonlinear optimization of
      parameters this allows a reliable automatic analysis of chromatograms with a
      large number of peaks, even with large groups of overlapping peaks. The analysis
      matches the quality of standard interactive methods, but still permits
      interactive refinement. This approach has been implemented and tested on a large
      set of data from chromatography of hydrocarbons in ambient air samples.

PMID- 15865200
TI  - Application of artificial neural network on mono- and sesquiterpenes compounds
      determined by headspace solid-phase microextraction-gas chromatography-mass
      spectrometry for the Piedmont ricotta cheese traceability.
AB  - Mono- and sesquiterpenes were used for the traceability of a typical Piedmont
      (Italy) mountain ricotta cheese produced by nine mountain farms. For each farm a
      sample of ricotta cheese was collected every 7 days during mountain grazing and
      analysed using headspace solid-phase microextraction-gas chromatography-mass
      spectrometry (SPME-GC-MS). Obtained results showed the presence of about 20
      monoterpenes (above all alpha-pinene, beta-pinene, camphene, p-cymene, beta
      myrcene and limonene) and about 15 sesquiterpenes such as alpha-caryophyllene,
      alpha-copaene and 9-epi-caryophyllene. Despite a wide concentration variability
      due to the stages of plant development and the pastured area, there are not able
      differences between the ricotta cheeses analysed so it is possible with the
      artificial neural network (ANN) technique to distinguish between different
      mountain farms.

PMID- 15865201
TI  - In situ analysis of the Martian soil by gas chromatography: decoding of complex
      chromatograms of organic molecules of exobiological interest.
AB  - Gas chromatography-mass spectrometry (GC-MS) will be used in future space
      exploration missions, in order to seek organic molecules at the surface of Mars,
      and especially potential chemical indicators of life. Carboxylic acids are among
      the most expected organic species at the surface of Mars, and they could be
      numerous in the analysed samples. For this reason, a chemometric method was
      applied to support the interpretation of chromatograms of carboxylic acid
      mixtures. The method is based on AutoCovariance Function (ACVF) in order to
      extract information on the sample--number and chemical structure of the
      components--and on separation performance. The procedure was applied to standard
      samples containing targeted compounds which are among the most expected to be
      present in the Martian soil: n-alkanoic and benzene dicarboxylic acids. ACVF was
      computed on the obtained chromatograms and plotted versus retention time: peaks
      of the ACVF plot can be related to specific molecular structures and are
      diagnostic for chemical identification of compounds.

PMID- 15865202
TI  - Computer language for identifying chemicals with comprehensive two-dimensional
      gas chromatography and mass spectrometry.
AB  - This paper describes a language for expressing criteria for chemical
      identification with comprehensive two-dimensional gas chromatography paired with
      mass spectrometry (GC x GC-MS) and presents computer-based tools implementing the
      language. The Computer Language for Indentifying Chemicals (CLIC) allows
      expressions that describe rules (or constraints) for selecting chemical peaks or
      data points based on multi-dimensional chromatographic properties and mass
      spectral characteristics. CLIC offers chromatographic functions of retention
      times, functions of mass spectra, numbers for quantitative and relational
      evaluation, and logical and arithmetic operators. The language is demonstrated
      with the compound-class selection rules described by Welthagen et al. [W.
      Welthagen, J. Schnelle-Kreis, R. Zimmermann, J. Chromatogr. A 1019 (2003) 233
      249]. A software implementation of CLIC provides a calculator-like graphical user
      interface (GUI) for building and applying selection expressions. From the
      selection calculator, expressions can be used to select chromatographic peaks
      that meet the criteria or create selection chromatograms that mask data points
      inconsistent with the criteria. Selection expressions can be combined with
      graphical, geometric constraints in the retention-time plane as a powerful
      component for chemical identification with template matching or used to speed and
      improve mass spectrum library searches.

PMID- 15865203
TI  - Chromatographic, capillary electrophoretic and matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry analysis of urinary modified
      nucleosides as tumor markers.
AB  - Modified nucleosides are formed posttranscriptionally in RNA. During RNA turnover
      free modified nucleosides are formed which circulate in the blood stream and are
      excreted in the urine. Their levels are increased in a number of malignant
      diseases, and they can be used in clinical chemistry as tumor markers. The
      analysis includes the isolation of the nucleosides from urine with phenylboronate
      gel and their separation and quantitation by HPLC on C18 columns or by capillary
      electrophoresis on uncoated columns applying a sodium dodecyl sulfate-borate
      phosphate buffer. Identification of the nucleosides is performed with matrix
      assisted laser desorption ionization time-of-flight mass spectrometry including
      post source decay spectra. In two clinical studies the diagnostic value of
      urinary modified nucleosides is investigated, in a study on children with
      leukemia and other malignant diseases and a study on women with breast cancer.
      Candidate markers are pseudouridine, 1-methylguanosine, N2-methylguanosine, 3
      methyluridine and 1-methyl-inosine.

PMID- 15865204
TI  - DNA recognition properties of the LHX3b LIM homeodomain transcription factor.
AB  - LHX3 is a LIM homeodomain transcription factor with established roles in
      pituitary and nervous system development. Mutations in the human LHX3 gene are
      associated with severe hormone deficiency diseases. Previous studies have shown
      that the human LHX3 gene produces at least three protein isoforms: LHX3a, LHX3b,
      and M2-LHX3. In gene activation assays, LHX3a and M2-LHX3 are significantly more
      active than LHX3b because the actions of LHX3b are repressed by an inhibitory
      domain in its amino terminus. In this report, we investigate the molecular
      characteristics that result in reduced transcriptional capacity of LHX3b by
      determining the optimal DNA binding preference of LHX3b. Site selection
      experiments using purified human LHX3b reveal that it selects AT-rich sequences
      that contain ATTA/TAAT motifs. The pool of sequences selected by LHX3b is similar
      to that selected by LHX3a but does not conform to as strict a consensus. Further,
      the LHX3b-selected sites are bound more avidly by LHX3a and M2-LHX3 suggesting
      that LHX3b does not act by recognizing LHX3b-specific binding sites in target
      genes. We conclude that the amino terminal repression domain of LHX3b mostly acts
      to reduce the transcriptional potency of LHX3 by inhibiting the DNA binding
      affinity of the homeodomain, with some reduction in DNA binding specificity.

PMID- 15865205
TI  - Overexpression of ERp29 in the thyrocytes of FRTL-5 cells.
AB  - It was previously reported that the up-regulation of ERp29 mRNA depends on the
      levels of thyroid stimulating hormone (TSH) in the thyrocytes of FRTL-5 cells. In
      order to investigate the putative new function of ERp29 as an endoplasmic
      molecular (ER) chaperone, an ERp29-overexpressing FRTL-5 cell line was
      established. This cell line had approximately three times the levels of ERp29
      protein and an enhanced level of thyroglobulin (Tg) secretion. The results showed
      both enhanced ERp29 expression and an interaction with the other ER chaperones
      such as GRP94, BiP, ERp72 and calnexin. In addition, ERp29 enhanced the
      expression of PKR-like ER kinase (PERK), which is a transmembrane protein located
      in the ER membrane. These findings suggest that ERp29 assists in protein folding
      as well as in the secretion of the secretory/plasma membrane proteins under close
      co-operation with other ER chaperones and the ER stress signaler, PERK.

PMID- 15865206
TI  - Carbon source-dependent regulation of a second gene encoding glutaredoxin from
      the fission yeast Schizosaccharomyces pombe.
AB  - Glutaredoxin (Grx), also known as thioltransferase (TTase), is an enzyme that
      catalyzes the reduction of a variety of disulfide compounds, including protein
      disulfides, in the presence of reduced glutathione. A second gene encoding Grx
      (Grx2) was cloned from the chromosomal DNA of the fission yeast
      Schizosaccharomyces pombe. The determined DNA sequence contains 1645 bp which is
      able to encode a polypeptide of 110 amino acids with a molecular mass of 12.2
      kDa. The genomic DNA consists of 4 exons and 3 introns. The isolated gene was
      found to produce functional glutaredoxin that could accelerate the growth of the
      fission yeast, and is highly expressed at the mid- and late exponential phases.
      Aluminum, cadmium and hydrogen peroxide marginally enhanced the synthesis of beta
      galactosidase from the Grx2-lacZ fusion gene. Shifts to lower concentrations
      (0.2, 0.4 or 0.8%) of D-glucose significantly enhanced the synthesis of beta
      galactosidase from the Grx2-lacZ fusion gene. And shifts to sucrose (0.2, 0.4,
      0.8 or 1.6%) as a sole carbon source markedly enhanced the synthesis of beta
      galactosidase from the Grx2-lacZ fusion gene, the degree of which was inversely
      dependent on concentration. However, nonfermentable carbon sources reduced the
      expression of the Grx2 gene due to their growth arrest. The transcription factor
      Pap1 is not involved in the basal expression and induction of the Grx2 gene. The
      Grx2 protein was subcellularly localized in the nucleus of the yeast cells. Our
      results indicate that the Grx2 protein, located in the nucleus, is linked with
      the yeast growth, and that the gene is regulated by carbon sources.

PMID- 15865207
TI  - Nonhomologous end-joining in a cell-free extract from the cultured silkworm cell
      line BmN4.
AB  - Nonhomologous end-joining (NHEJ) is one of the repair pathways for double-strand
      breaks (DSBs) in eukaryotic cells. By using linearized plasmid substrates, we
      have detected intramolecular NHEJ activity in a cell-free extract from the
      cultured silkworm cell line BmN4. The efficiency of NHEJ differed according to
      the structure of DNA ends; approximately 1% of input DNA was repaired when the
      substrate had cohesive ends. The reaction required the hydrolysis of nucleotide
      triphosphate; interestingly, all of four rNTPs or four dNTPs could support the
      reaction. A substrate with non-complementary DNA ends was mainly repaired by the
      DNA polymerase-mediated pathway. These results indicate that the present cell
      free system will be useful to analyze the molecular mechanisms of DSB repair and
      NHEJ in insect cells.

PMID- 15865208
TI  - Cloning, expression and chromosomal assignment of human pleckstrin 2.
AB  - We report the isolation of human pleckstrin 2 cDNA. The cDNA contains a 1059 bp
      open reading frame encoding a polypeptide of 353 amino acid residues. The deduced
      amino acid sequence indicates that pleckstrin 2 contains two pleckstrin homology
      domains and a DEP (dishvelled, egl-10, and pleckstrin) domain and had a 95%
      identity with the sequence of mouse pleckstrin 2. Northern blot and a reverse
      transcription-coupled polymerase chain reaction analysis revealed that pleckstrin
      2 mRNA is widely expressed in a variety of cell lines. The chromosomal location
      of the mouse pleckstrin 2 gene was on the D3 band of chromosome 12, as determined
      by fluorescence in situ hybridization and the human pleckstrin 2 gene was mapped
      to chromosome 14q24.1 by a bioinformatics analysis.

PMID- 15865209
TI  - Characterization of a human regulatory subunit of protein phosphatase 3 gene
      (PPP3RL) expressed specifically in testis.
AB  - Protein phosphatase 3 (PPP3, formerly PP2B, Calcineurin), a serine/threonine
      protein phosphatase, is a heterodimer composed of one catalytic subunit (PPP3C,
      Calcineurin A) and one regulatory subunit (PPP3R, Calcineurin B). PPP3R, an EF
      hand Ca2+ binding protein, contains four high-affinity EF-hand calcium-binding
      sites, indicating that PPP3 plays critical roles in many calcium-mediated signal
      transduction pathways. PPP3R has two isoforms, PPP3R1 (also known as PP2Bbeta1)
      and PPP3R2 (also known as PP2BB2). While PPP3R1 is ubiquitously expressed in
      different tissues, PPP3R2 is exclusively expressed in testis. PPP3R2 has only
      been identified in rat and mouse. Here we report a human homologue of PPP3R2,
      which is designated PPP3RL (PPP3R like protein). PPP3RL gene was predicated to
      encode 171 amino acid residues with four EF-hand calcium-binding domains and this
      putative protein shares 82.9% and 80.5% identity with PPP3R2 of rat and mouse,
      respectively. Our results show that PPP3RL gene localizes to human chromosome
      9q22 and transcripts of PPP3RL gene are specifically expressed in the testis,
      moreover, this tissue-specific expression is due to demethylation of its promoter
      region in testis.

PMID- 15865210
TI  - Cloning and characterization of a novel human homolog* of mouse U26, a putative
      PQQ-dependent AAS dehydrogenase.
AB  - Mouse U26 has been defined as a 2-aminoadipic 6-semialdehyde dehydrogenase. It
      was speculated to be a PQQ-dependent AAS dehydrogenase due to the research of
      demonstrating PQQ as a new B vitamin. We isolated a novel human cDNA from the
      human fetal brain cDNA library we constructed. Its deduced protein was most
      related to mouse U26. Thus, we termed it human U26. This putative protein
      contains an AMP-binding domain, a Phosphopantetheine-binding domain and six PQQ
      binding motifs. Human U26 mRNA is ubiquitously expressed in adult tissues and is
      highly expressed in colon adenocarcinoma (CX-1) and colon adenocarcinoma (GI-112)
      cell lines. Further study should be made to clarify the precise function of human
      U26.

PMID- 15865211
TI  - Calmodulin genes in zebrafish (revisited).
AB  - Calmodulin (CaM), a ubiquitous protein, ancestral in early eukaryotes, regulates
      a large number of physiologically important functions by activating other
      proteins, some of them enzymes, usually in response to changes in the local
      concentration of calcium ions. Invertebrates possess one gene that codes for CaM.
      Among vertebrates, mammals display three genes that code for a 100% identical CaM
      molecule, while for zebra fishes etc., a non-mammalian vertebrate, we reported
      earlier the existence of four such genes. The number of multiple genes coding for
      a 100% identical CaM molecule present in the zebra fish genome, however, is
      corrected here, from the four, as previously suggested, to six (alpha, alpha2,
      beta, beta2, gamma and gamma 2). Identification of each of these genes is readily
      achieved upon examination of the characteristic 5' and 3' UTRs within their
      respective mRNAs even though we do not know at present what role these UTRs might
      play. A scanning of the 3' UTRs for short homology elements among the six genes
      (and a comparison with the human type I, II, and III CaM 3' UTRs) also suggests
      that duplication processes for three genes resulted in the formation of six such
      genes. As they become available, the promoter regions for these six genes should
      be scanned for possible identification of putative regulatory elements if we are
      to understand the need for the uniquely rigid evolutionary maintenance of these
      six genes. A comparison of the promoter regions for the beta and beta 2 genes is
      presented in this paper. A few common short homologous elements appear to be
      retained in these generally highly variant two regions, but conclusions about
      differential expression controls must be delayed until the promoter regions for
      all the other CaM genes have been examined.

PMID- 15865212
TI  - Intragenomic variation in ribosomal RNA gene of the sea urchin Lytechinus
      variegatus.
AB  - The first series of studies on the rDNA satellite of the sea urchin, Lytechinus
      variegatus, based on saturation hybridization of rRNA-rDNA and renaturation
      kinetics, showed that repeat length of rRNA gene was of about 8 kb in which there
      was no provision for NTS. The EM denaturation mapping, however, revealed (1) that
      the gene was 75% larger (longer) than 8 kb, within which there was a NTS whose
      length varied in repeating units, (3) and there was a region of high GC almost in
      the middle of the transcribed part. The suggestion of length and sequential
      heterogeneity in the gene copies coming from the first denaturation mapping
      prompted further studies with techniques so that the conclusions of the previous
      results could be stated with finality. The results that emanated from further
      studies established that the rDNA repeat length of L. variegatus was of about 12
      kb and that the NTS ranged from 3.8 to 6.4 kb. Earlier demonstration of a
      moderately high-GC segment within the transcribed part was also confirmed by
      sequence analysis. However, the stipulations on the NTS regarding sequential and
      length heterogeneity, still awaits elucidation by sequence analysis.

PMID- 15865213
TI  - Area-under-the-curve for peginterferon alpha-2a and peginterferon alpha-2b is not
      related to body weight in treatment-naive patients with chronic hepatitis C.
AB  - One reason for dosing a drug by body weight is to reduce interpatient variability
      in clinical response. This study evaluated the relationship between body weight
      and drug exposure for peginterferon alpha-2a and peginterferon alpha-2b used in
      combination with ribavirin for treating patients with chronic hepatitis C. These
      two products are dosed differently: peginterferon alpha-2a is flat-dosed at 180
      microg regardless of body weight, whereas peginterferon alpha-2b is dosed by body
      weight at 0.5-1.5 microg/kg. Bodyweight dosing of peginterferon alpha-2b is
      purported to overcome the adverse effect of increased body weight on sustained
      virological response. To test this hypothesis, we measured the area-under-the
      curve (AUC) for both drugs as part of a previously reported pharmacokinetics
      study. In total, 22 interferon-naive patients with chronic hepatitis C were
      treated for 12 weeks. Patients were randomly assigned in a 1:1 ratio to receive
      once-weekly peginterferon alpha-2a 180 microg (n=10) or peginterferon alpha-2b
      1.0 microg/kg (n=12). Ribavirin was dosed by body weight at 1000 mg/day (< or =
      75kg) or 1200 mg/day (> 75 kg). We found no correlation between body weight and
      AUC for either peginterferon alpha-2a or peginterferon alpha-2b. Considerable
      interpatient variability in AUC occurred for peginterferon alpha-2a [coefficient
      of variation (CV): 37.5%] and, despite dosing by body weight, for peginterferon
      alpha-2b (CV: 36.8%). Thus, there appears to be no rationale for a body-weight
      dosing regimen for peginterferon alpha-2a, and such dosing does not achieve more
      consistent AUC measurements in patients receiving peginterferon alpha-2b.

PMID- 15865214
TI  - Altered adipokine response in murine 3T3-F442A adipocytes treated with protease
      inhibitors and nucleoside reverse transcriptase inhibitors.
AB  - BACKGROUND: Abnormal levels of tumour necrosis factor (TNF)-alpha, interleukin
      (IL)-6 and adiponectin have been observed in HIV patients with lipodystrophy.
      However, because these patients have long drug and disease histories, it is
      unclear which drugs are responsible for these abnormalities. We have therefore
      investigated the effects of individual antiretrovirals on adipokine expression
      and adipogenesis using a murine cell line in vitro. METHODS: Differentiating
      murine 3T3-F442A adipocytes were incubated with 20 microM nucleoside reverse
      transcriptase inhibitors (NRTIs) zidovudine or stavudine, or protease inhibitors
      (PIs) indinavir, ritonavir, saquinavir or nelfinavir, in the presence and absence
      of rosiglitazone (10 microM). Adipogenesis was assessed using glycerol-3
      phosphate dehydrogenase activity, while expression of TNF-alpha, IL-6 and
      adiponectin at protein and mRNA levels was assessed by ELISA and quantitative
      real-time PCR, respectively. RESULTS: Nelfinavir, ritonavir and saquinavir
      inhibited adipogenesis and up-regulated the expression of TNF-alpha and IL-6, but
      this effect was not seen with indinavir, zidovudine and stavudine. Adiponectin
      expression was significantly reduced in both NRTI- and PI-treated cells, although
      the most profound reductions were found with ritonavir and saquinavir. Co
      incubation with rosiglitazone led to a partial attenuation of the change in TNF
      alpha, IL-6 and adiponectin secretion. CONCLUSIONS: Our data suggest that the PIs
      nelfinavir, ritonavir and saquinavir have potent effects in inhibiting adipocyte
      differentiation whilst up-regulating TNF-alpha and IL-6 mRNA levels and
      decreasing adiponectin levels. These changes were partially attenuated by
      rosiglitazone. Taken together, the data show that antiretrovirals have complex
      effects on adipocyte function, which may be mediated by an altered adipokine
      response.

PMID- 15865215
TI  - The HIV protease inhibitors nelfinavir and saquinavir, but not a variety of HIV
      reverse transcriptase inhibitors, adversely affect human proteasome function.
AB  - BACKGROUND: In HIV-infected patients some clinical and immunological benefits of
      antiretroviral therapy, which frequently include a combination of HIV protease
      inhibitors (PIs) and reverse transcriptase inhibitors (RTIs), cannot be solely
      explained by the drugs' action on viral enzymes. Proteasomes constitute the
      central protease of the ubiquitin ATP-dependent pathway involved in many cellular
      processes, as well as in HIV maturation and aggressiveness. OBJECTIVE: To explore
      whether the PIs nelfinavir and saquinavir and the RTIs abacavir, nevirapine,
      delavirdine, stavudine and didanosine affect proteasome function in vitro and in
      vivo. METHODS: Peptidase activity of purified human 26S and 20S proteasomes was
      assayed with and without the drugs at different concentrations. Intracellular
      proteasome proteolytic activity was evaluated by searching for ubiquitin-tagged
      proteins in HL60 cells incubated with and without the drugs. RESULTS: At
      therapeutic dosages, nelfinavir and saquinavir inhibited proteasome peptidase
      activity and caused intracellular accumulation of polyubiquitinated proteins, a
      hallmark of proteasome proteolytic inhibition in vivo; the RTIs failed to evoke
      either effect. CONCLUSION: Proteasomes are targeted by the two PIs but not the
      RTIs. Therefore, in HIV-infected patients the beneficial effect of a therapy
      including one of the two PIs should partly rely on inhibition of host proteasome
      function.

PMID- 15865216
TI  - In vitro susceptibility of adenovirus to antiviral drugs is species-dependent.
AB  - Adenovirus infections are a frequent and serious complication following
      allogeneic haematopoietic stem cell transplantation (HSCT). The antiviral drugs
      cidofovir and ribavirin have been used as first-line therapy for disseminated
      infections with variable results. In the present study, in vitro susceptibility
      to these two drugs was evaluated on HEp-2 cells in adenovirus reference strains
      representing serotypes of each of the six species and in clinical isolates.
      Susceptibility to cidofovir was comparable between species with inhibition of
      replication of all tested serotypes in a narrow dose range (IC50=17-81 microM).
      However, susceptibility to ribavirin was highly dependent on the species.
      Serotypes from species A, B, D, E and F were all resistant to ribavirin (IC50=396
      to >500 microM). Only replication of serotypes from species C was inhibited by
      ribavirin (IC50=48-108 microM). This species-dependent susceptibility of
      adenovirus to ribavirin was confirmed in clinical isolates. When tested on other
      cell lines (PLC, A549 and 293), all species were revealed to be resistant to
      ribavirin. If our in vitro findings are predictive of virological responses in
      vivo, these results suggest that ribavirin would not be effective for management
      of non-C species adenovirus infections after HSCT.

PMID- 15865217
TI  - Sensitivity of primary R5 HTV-1 to inhibition by RANTES correlates with
      sensitivity to small-molecule R5 inhibitors.
AB  - In approximately 50% of HIV-1 subtype B-infected individuals, progression to AIDS
      is preceded by the emergence of CXCR4-using (X4) variants, whereas the rest
      progress to AIDS in the presence of CCR5-using (R5) variants only. In a previous
      study, we showed that during disease progression in the presence of R5 variants
      only, HIV-1 variants emerge with a decreased sensitivity to inhibition by RANTES,
      a natural ligand of CCR5 that inhibits cellular entry of R5 variants. This
      observation was of potential clinical relevance as HIV-1 small-molecule R5 entry
      inhibitors are a new class of drugs that, in analogy to RANTES, target the
      binding and subsequent entry of HIV into the target cell. Here we show that R5
      HIV-1 sensitivity to RANTES correlates with sensitivity to the R5 small-molecule
      inhibitor AD101. HIV-1 small-molecule entry inhibitors are a new class of drugs
      that target the binding and subsequent entry of HIV into the target cell.
      Furthermore, we found that R5 variants obtained from individuals who later
      developed X4 variants were less sensitive to AD101 inhibition compared with R5
      variants obtained from individuals who never developed X4 variants. These results
      may have implications for the evaluation of R5 inhibitors in future clinical
      trials.

PMID- 15865218
TI  - Plasma pharmacokinetics of once- versus twice-daily lamivudine and abacavir:
      simplification of combination treatment in HIV-1-infected children (PENTA-13).
AB  - BACKGROUND: There are few data on plasma and intracellular pharmacokinetics (PK)
      of once-daily (q24h) nucleoside analogues in HIV-infected children. METHODS:
      Children aged 2-13 years receiving combination treatment containing lamivudine
      (3TC) (4 mg/kg) and/or abacavir (ABC) (8 mg/kg) twice daily (q12h) were included
      in this single-arm, open-label, crossover study. Intensive plasma PK sampling was
      performed at steady state, after which children switched to q24h dosing and PK
      sampling was repeated 4 weeks later. Daily area under the curve (AUC0-24) and
      peak level (Cmax) of q24h and q12h regimens were compared by geometric mean
      ratios (GMRs) with 90% confidence intervals (CIs). Children were followed for 24
      weeks to evaluate safety and virological response. RESULTS: 24 children were
      enrolled, of whom 20 [median age (range) 5.6 (2.1-12.8) years] had evaluable PK
      data for 3TC (n=19) and/or ABC (n=14). GMRs of 3TC and ABC AUC0-24 and Cmax q24h
      versus q12h significantly exceeded 1.0. GMRs were not significantly different
      between children aged 2-6 versus 6-13 years old (P>0.08). Of note, 3TC Cmax
      values for both q12h and q24h were significantly lower in children aged 2-6
      versus 6-13 years old. No child discontinued due to adverse events. At baseline,
      16 out of 20 children had a viral load <100 copies/ml compared with 17 out of 19
      at week 24. CONCLUSION: AUC0-24 and Cmax of both 3TC and ABC q24h were not
      inferior to q12h dosing in children. Insufficient results were obtained
      concerning intracellular levels of the active triphosphate moieties of both
      agents. Virological data did not indicate a marked difference in antiviral
      activity between q12h and q24h regimens.

PMID- 15865219
TI  - Impact of human immunodeficiency virus type 1 subtype on first-line
      antiretroviral therapy effectiveness.
AB  - OBJECTIVE: The effectiveness of antiretroviral treatment (ART) was compared in
      416 naive patients from a French clinical cohort infected with B and non-B HIV-1
      subtypes. METHODS: Time to HIV viral load (VL) undetectability was calculated for
      each subtype group. Three other parameters were estimated 3, 6 and 12 months
      after enrolment: clinical progression (that is, AIDS-defining events or death),
      changes in CD4 cell counts from baseline and proportion of patients achieving an
      undetectable VL (<400 HIV-RNA copies/ml). RESULTS: In this cohort, 317 patients
      (76%) were infected with a B subtype and 99 (24%) with a non-B subtype. Median
      time to VL undetectability was similar in the B subtype group [147 days, 95%
      confidence interval (CI) 119-165] and non-B subtype group (168 days, 95% CI: 105
      234; P=0.16). After adjusting for AIDS-defining events at enrolment, baseline CD4
      cell counts and VL, and for the treatment on which patients were initiated, no
      association was found between HIV subtypes and time to VL undetectability (B
      subtype vs non-B subtype: hazard ratio=0.80, 95% CI: 0.62-1.02, P=0.07). In the
      3, 6 and 12 months after enrolment, subtype had no impact on clinical
      progression, CD4 cell count or VL responses to ART. This suggests that B and non
      B subtypes do not affect first-line therapy efficacy, which is encouraging in
      view of the worldwide spread of non-B HIV-1 subtypes and the increasing
      availability of ART in developing countries. However, in this study we did not
      take into account individual non-B subtype species, therefore further studies
      should be designed to evaluate the efficacy of these regimens in patients with
      particular non-B subtypes.

PMID- 15865220
TI  - Pre-incubation of cell-free HIV-1 group M isolates with non-nucleoside reverse
      transcriptase inhibitors blocks subsequent viral replication in co-cultures of
      dendritic cells and T cells.
AB  - In order to study the inhibitory effect of various reverse transcriptase
      inhibitors (RTIs) on cell-free HIV, we adapted a recently described in vitro
      system, based on co-cultures of dendritic cells and resting CD4 T cells,
      modelling early target cells during sexual transmission. The compounds tested
      included the second-generation non-nucleoside RTI (NNRTI) TMC-120 (R147681,
      dapivirine) and TMC-125 (R165335, travertine), as well as the reference
      nucleoside RTI AZT (zidovudine), the nucleotide RTI PMPA (tenofovir) and the
      NNRTI UC-781. The virus strains included the reference strain HIV-1Ba-L and six
      primary isolates, representative of the HIV-1 group M pandemic. They all display
      the non-syncytium-inducing and CCR5 receptor-using (NSI/R5) phenotype, important
      in transmission. Cell-free virus was immobilized on a poly-L-lysine (PLL)-treated
      microwell plate and incubated with compound for 1 h. Afterwards, the compound was
      thoroughly washed away; target cells were added and cultured for 2 weeks,
      followed by an extended culture with highly susceptible mitogen-activated T
      cells. Viral production in the cultures was measured on supernatant with HIV
      antigen ELISA. Negative results were confirmed by showing absence of proviral DNA
      in the cells. TMC-120 and TMC-125 inhibited replication of HIV-1Ba-L with average
      EC50 values of 38 nM and 117 nM, respectively, whereas the EC50 of UC-781 was 517
      nM. Complete suppression of virus and provirus was observed at compound
      concentrations of 100, 300 and 1000 nM, respectively. Inhibition of all primary
      isolates followed the same pattern as HIV-1Ba-L. In contrast, pre-treating the
      virus with the nucleotide RTI PMPA and AZT failed to inhibit infection even at a
      concentration of 100000 nM. These data clearly suggest that NNRTIs inactivate RT
      enzymatic activity of different viral clades (predominant in the epidemic) and
      might be proposed for further testing as a sterilizing microbicide worldwide.

PMID- 15865222
TI  - A study to investigate the impact of the initiation of highly active
      antiretroviral therapy on the hepatitis C virus viral load in HIV/HCV-coinfected
      patients.
AB  - Changes in the hepatitis C virus (HCV) viral load (VL) were assessed in a
      retrospective study of 50 HIV/HCV-coinfected patients who initiated highly active
      antiretroviral therapy (HAART). Most patients responded to HAART [during the
      first 6 months, plasma HIV VL fell by a mean 1.39 log10, becoming undetectable
      (<400 copies/ml) in 22% and CD4+ T cells increased by a mean of 100
      cells/microl], but surprisingly, 27 (54%) showed some rise and 25 (50%) showed a
      significant increase in the HCV VL. This figure was considered to be a minimum
      estimate. A majority of the patients showed an increase of less than 1 log10 that
      was associated with a rapid decrease in the HIV VL, whereas an increase in the
      HCV VL of greater than 1 log10, noted in eight patients, was associated with a
      baseline CD4+ cell count of less than 200 cells/microl. The increase in the HCV
      VL was not associated with hepatitis as determined by raised alanine transferase.

PMID- 15865221
TI  - Dynamic changes in clinical features and cytokine/chemokine responses in SARS
      patients treated with interferon alfacon-1 plus corticosteroids.
AB  - Severe acute respiratory syndrome (SARS), caused by a novel coronavirus, emerged
      in early 2003 as a major international health crisis. We report on serum cytokine
      levels, viral load and clinical parameters over the course of the disease in a
      cohort of nine adult SARS patients treated with steroids and interferon alfacon-1
      at North York General Hospital in Toronto, Ontario. Considerable variation among
      SARS patients with respect to circulating viral load and patterns of SARS-CoV
      evoked cytokine responses was recorded. No single cytokine profile was observed
      in all patients, yet serum concentrations of interferon (IFN)-gamma, interleukin
      (IL)-10, CXCL10, CCL5 and CXCL8 were found to be elevated above normal levels
      during the course of the disease in all patients. Expression levels for IL-10,
      IFN-gamma and CXCL10 consistently peaked within 4 days of peak viral load. IL
      12p70, IL-4 and tumour necrosis factor-alpha concentrations were consistently
      highest within 5 days of peak viral load. These results suggest that elevated
      levels of inflammatory cytokines are sensitive correlates of disease severity,
      including lung abnormalities and viral load in serum, and may provide a tool for
      monitoring disease progression in affected individuals.

PMID- 15865223
TI  - Therapeutic vaccination of HIV-1-infected patients on HAART with a recombinant
      HIV-1 nef-expressing MVA: safety, immunogenicity and influence on viral load
      during treatment interruption.
AB  - The safety and immunogenicity of an HIV-1 nef-expressing modified vaccinia virus
      Ankara (MVA) was investigated in 14 HIV-1-positive patients (CD4 >400/microl) on
      highly active antiretroviral therapy (HAART). Patients were vaccinated at weeks
      0, 4 and 16, followed by interruption of HAART at week 18. MVA-nef was well
      tolerated except for local reactions, with only mild systemic side effects
      reported in a few patients. Vaccination with MVA-nef was associated with
      recognition of new HIV-1 T-cell epitopes (cytotoxic T-lymphocyte epitopes in 9/14
      patients, CD4 epitope/recombinant Nef protein in 2/14) and an increase in CD4+
      and CD8+ T cells. All patients had been vaccinated against smallpox and a strong
      T-cell and antibody response to MVA was induced in all patients. After
      interruption of HAART, viral load rebounded in all patients, but after a median
      time of 36 (4-76) weeks in 9/14 patients, viraemia remained below the pre-HAART
      viral load and CD4 counts stayed above the pre-HAART levels. While six patients
      have remained off therapy for a median time of 64 (57-76) weeks, HAART was
      resumed in 8/14 patients after a median treatment interruption time of 15 (4-38)
      weeks. This study has demonstrated that MVA-nef is safe and immunogenic in HIV-1
      infected subjects and has provided encouraging data on the potential of
      therapeutic vaccinations.

PMID- 15865224
TI  - Pharmacokinetics of reduced-dose indinavir/ritonavir 400/100 mg twice daily in
      HIV-1-infected Thai patients.
AB  - OBJECTIVE: To study the pharmacokinetics of indinavir/ ritonavir 400/100 mg twice
      daily in antiretroviral-naive patients at Srinagarind Hospital in Khon Kaen,
      Thailand. METHODS: This was a steady-state, open-label pharmacokinetic study of
      19 patients. A 12 h pharmacokinetic curve was recorded after an overnight fast.
      Plasma levels of indinavir and ritonavir were determined by a validated HPLC
      method. Virological failure was defined according to the most recent US
      Department of Health and Human Services guidelines as a viral load above 400
      copies/ml at week 24. RESULTS: Median baseline values for CD4 and viral load were
      13cells/mm3 and 167000 copies/ml, respectively. The median (interquartile ranges)
      for indinavir AUC, Cmax and Cmin were 18.1 (15.3-23.8) mg/l x h, 4.1 (3.6-4.8)
      mg/l and 0.17 (0.12-0.30) mg/l, respectively. These values represent 37%, 39% and
      24% of the AUC, Cmax and Cmin values found, respectively, for the
      indinavir/ritonavir 800/100 mg dose in HIV-1-infected Thai patients. Short-term
      virological response was satisfactory. There were three subjects with an
      indinavir Cmin. below the target value of 0.10 mg/l, of whom one had virological
      failure (33%). Among the other 16 subjects with an indinavir Cmin above 0.10
      mg/l, there was also one virological failure (6%) (P=0.30). CONCLUSIONS:
      Indinavir exposure in this reduced-dose regimen of 400 mg with 100 mg ritonavir
      twice daily was more than dose-proportionally lower than previously observed with
      the indinavir/ritonavir 800/100 mg twice daily regimen. Therapeutic Cmin levels
      of indinavir were achieved in >80% of the subjects and short-term virological
      response was satisfactory in this cohort of patients starting highly active
      antiretroviral therapy at an advanced disease stage with high baseline viral
      loads.

PMID- 15865225
TI  - Open, randomized, multicentre italian trial on PEG-IFN plus ribavirin versus PEG
      IFN monotherapy for chronic hepatitis C in HIV-coinfected patients on HAART.
AB  - BACKGROUND: Chronic hepatitis C is common and aggressive in HIV-positive
      patients, so the development of a well-tolerated HCV therapy is a priority. We
      evaluated the efficacy and safety of pegylated interferon alpha2b (PEG-IFN) plus
      ribavirin (RBV) versus PEG-IFN monotherapy in HIV/HCV-coinfected patients
      undergoing highly active antiretroviral therapy (HAART), and analysed the
      predictive factors of response. METHODS: An Italian, multicentre, open-label
      trial including 135 coinfected patients, randomized to PEG-IFN 1.5 microg/kg/week
      plus RBV 400 mg twice daily (n=69, arm A) or PEG-IFN 1.5 microg/kg/week (n=66,
      arm B) for 48 weeks. We assessed the predictive values of early virological
      response (EVR) at week 8 (HCV-RNA drop >2 log10 compared with baseline or
      undetectable levels) on sustained virological response (SVR). RESULTS: Fifty-five
      patients (28 from arm A and 27 from arm B) completed 48 weeks of therapy. At the
      end of treatment, 20/28 patients in arm A and 11/27 in arm B had HCV-RNA <50
      IU/ml. In a per-protocol analysis, SVR was reached by 54% of patients in arm A
      (genotype 2-3, 11/16; genotype 1-4, 4/12) and 22% in arm B (genotype 2-3, 3/15;
      genotype 1-4, 3/12). In an intention-to-treat analysis, the SVR was 22% in arm A
      (genotype 2-3, 11/32; genotype 1-4, 4/37) versus 9% in arm B (genotype 2-3, 3/32;
      genotype 1-4, 3/34). The best predictors of SVR were the use of combination
      therapy, infection with HCV genotype 3 versus genotype 1, and EVR at week 8.
      Thirty patients (15 from arm A and 15 from arm B) dropped out of the trial
      prematurely due to side effects. The positive predictive value of EVR at week 8
      was 65%, the negative predictive value was 86%. CONCLUSIONS: PEG-IFN plus RBV can
      be considered a solid option for the treatment of HIV/HCV-coinfected patients.
      The key to successfully improving efficacy is strong compliance through strict
      overall patient monitoring, in order to best manage drug toxicity. EVR assessment
      at week 8 may become a useful stategy in the management of therapy.

PMID- 15865226
TI  - Lamivudine treatment in HBeAg-negative chronic hepatitis B patients with low
      level viraemia.
AB  - BACKGROUND: Our aim was to determine the short-term natural course of viraemia
      and the response to lamivudine treatment in HBeAg-negative chronic hepatitis B
      patients with a persistently low hepatitis B virus (HBV)-DNA level. METHODS: A
      total of 55 patients were included. Group 1 consisted of 37 patients with low
      level viraemia and high serum alanine aminotransferase (ALT) levels and further
      randomized to two groups: group 1a (n=19) patients received 1 year of lamivudine
      therapy and group 1b (n=18) patients were untreated controls. Group 2 consisted
      of 18 inactive carriers who were followed as controls of untreated low viraemic
      chronic hepatitis B patients. HBV DNA was longitudinally determined by real-time
      polymerase chain reaction assay. RESULTS: A female predominance in group 2 was
      observed while males were predominant in group 1. Mean age and baseline HBV-DNA
      levels did not differ between group 1 and 2 patients while group 1 patients had a
      higher histological score (P<0.01). Of group 1a patients, 44% had complete ALT
      normalization at end of treatment, whereas 21% untreated group 1b patients had
      normal ALT at the end of the follow-up. No change in histological activity was
      observed in group 1a patients at the end of treatment. HBV-DNA levels did not
      significantly change from baseline to end-of-treatment/observation period in
      patient groups. The viraemia course was not different across the groups.
      CONCLUSIONS: Low viraemic HBeAg-negative patients with high ALT present with
      minimal/mild histological activity. Inactive carriers cannot be differentiated
      from low viraemic patients with high ALT based on HBV DNA determination. Although
      lamivudine treatment can be effective in some cases, observation rather than a
      prompt treatment attempt seems to be more logical because of mild histological
      changes and low response rate to treatment in these patients.

PMID- 15865227
TI  - Mitochondrial toxicity of nucleoside analogues in primary human lymphocytes.
AB  - OBJECTIVE: To evaluate if nucleoside analogue reverse transcriptase inhibitors
      (NRTIs) and polymerase-gamma inhibitors deplete mitochondrial DNA (mtDNA) in
      cultured primary lymphocytes and if such depletion might be associated with
      functional defects. METHODS: Primary peripheral blood CD4 and CD8 lymphocytes
      were purified from six healthy humans (three male and three female), stimulated
      mitotically (CD3/CD28) and cultured for 10 days in the presence or absence of
      NRTIs. Lymphocyte proliferation, mtDNA content, the expression of mtDNA-encoded
      cytochrome c-oxidase II (COXII) and lactate production were assessed. RESULTS: In
      CD4 lymphocytes, 10-day exposure to zalcitabine (1.77 microM), didanosine (118
      microM) and stavudine (361 microM) induced a time-dependent decline of mtDNA.
      Compared with controls, residual mtDNA levels were 25%, 21% and 40%,
      respectively. COXII was reduced to 55%, 35% and 70% of control values. Lactic
      acid production was increased (by 214%, 294% and 175%, respectively). At day 10,
      lymphocyte counts were reduced (to 60%, 51%, and 41%, respectively). Zidovudine
      (71 microM) also reduced lymphocyte counts to 34% and increased lactic acid
      production by 170%, but did not induce mtDNA and COXII depletion. All these
      changes were highly significant. Lower NRTI concentrations (0.177 microM of
      zalcitabine, 11.8 microM of didanosine, 3.6 microM of stavudine and 7.1 microM of
      zidovudine) had effects at the border of significance. Similar observations were
      made in CD8 lymphocytes. CONCLUSIONS: In human lymphocytes, zalcitabine,
      didanosine and stavudine induce dose- and time-dependent mtDNA depletion, which
      is associated with decreased cell proliferation and increased lactate production.
      Zidovudine impairs lymphocyte division without inducing mtDNA depletion.

PMID- 15865228
TI  - Field assessment of generic antiretroviral drugs: a prospective cohort study in
      Cameroon.
AB  - OBJECTIVE: To assess the effectiveness of generic anti-retroviral drugs in terms
      of survival and virological and immunological responses, as well as their
      tolerability and the emergence of viral resistance. METHODS: A total of 109 HIV-1
      infected patients were enrolled in a prospective cohort study in Yaounde,
      Cameroon. Available generic drugs were a fixed-dose combination (FDC) of
      zidovudine (ZDV) and lamivudine (3TC), an FDC of 3TC, stavudine (d4T) and
      nevirapine (NVP), and individual formulations of ZDV, 3TC and NVP. RESULTS: At
      baseline, the median CD4 cell count was 150/mm3 [interquartile range (IQR) 61
      223] and median viral load was 5.4 log10 copies/ml (IQR 4.8-5.6); 78% of patients
      received ZDV/3TC/NVP and 22% received 3TC/d4T/NVP. Median follow-up was 16 months
      (IQR 11-23). The survival probability was high (0.92 at 12 months); plasma viral
      load declined by a median of 3.3 log10 copies/ml and 86.9% of the intention-to
      treat population had viral load <400 copies/ml at 12 months; CD4 count had
      increased by a median of 106 cells/mm3 at 12 months; drug resistance rarely
      emerged (incidence rate 3.2 per 100 person-years); and the treatments were
      reasonably well-tolerated (incidence rate of severe adverse effects 7.8 per 100
      person-years). CONCLUSION: Together with previous pharmacological and clinical
      studies, this prospective study suggests that these generic antiretroviral drugs
      can be used in developing countries.

PMID- 15865229
TI  - In vitro combination studies of tenofovir and other nucleoside analogues with
      ribavirin against HIV-1.
AB  - In patients coinfected and treated for both HIV-1 and hepatitis C virus (HCV),
      administration of ribavirin (RBV) may result in altered intracellular drug levels
      of nucleoside reverse transcriptase inhibitors through inhibition of inosine 5'
      monophosphate dehydrogenase. Drug interactions between tenofovir and RBV were
      studied in vitro in order to provide insights into the safety of co
      administration of tenofovir disoproxil fumarate (DF) and RBV in HCV/HIV-1
      coinfected patients. In accordance with previous in vitro studies, strongly
      increased anti-HIV activity was observed when RBV was combined with didanosine
      (ddl). In contrast, low-level anti-HIV antagonism was observed when RBV was
      combined with either tenofovir or abacavir. Significantly stronger anti-HIV
      antagonism was observed when RBV was combined with either zidovudine, stavudine,
      emtricitabine or lamivudine. Thus, although tenofovir and ddl are both adenosine
      analogues, their in vitro interactions with RBV are markedly different. These
      results suggest a low potential for increased toxicity upon co-administration of
      tenofovir DF with RBV in patients.

PMID- 15865230
TI  - The steady-state pharmacokinetics of nelfinavir in combination with tenofovir in
      HIV-infected patients.
AB  - BACKGROUND: The nucleotide analogue, tenofovir, has been shown to lower plasma
      atazanavir levels in pharmacokinetic trials, an interaction that may be partly
      reversed by the addition of ritonavir, whereas plasma tenofovir levels are
      themselves raised when the drug is combined with lopinavir/ritonavir. OBJECTIVE:
      To investigate the effect of tenofovir coadministration on the steady-state
      pharmacokinetics of nelfinavir in HIV-infected patients. METHODS: Eighteen
      patients received nelfinavir 1250 mg twice daily plus prescribed nucleoside
      reverse transcriptase inhibitors for at least 14 days, with pharmacokinetic
      measurements performed on day 15. Treatment with nelfinavir was continued for
      another 7 days with the addition of 300 mg tenofovir once daily. Pharmacokinetic
      measurements were repeated on day 22. Plasma samples were analysed by liquid
      chromatography-tandem mass spectrometry for nelfinavir, its primary metabolite,
      M8, and tenofovir. The parameters AUC0-12, C0, Cmax and Tmax were compared for
      nelfinavir with and without tenofovir by calculating geometric mean ratios (GMRs)
      of the pharmacokinetic parameters with associated 95% confidence intervals (95%
      CIs). Safety was assessed throughout the study. RESULTS: The addition of
      tenofovir to the nelfinavir-based regimen had no effect on the pharmacokinetics
      of nelfinavir. The GMR of the nelfinavir AUC0-12 values was 0.97 (95% CI: 0.80
      1.17). There was a slight decrease in M8 metabolite (AUC0-12 ratio, 0.87; 95% CI:
      0.68-1.11) but this was not significant. No serious adverse events occurred
      through the study period. CONCLUSION: Nelfinavir does not require dose adjustment
      when coadministered with tenofovir and appears to be well-tolerated by HIV
      infected patients.

PMID- 15865231
TI  - The influence of the M184V mutation in HIV-1 reverse transcriptase on the
      virological outcome of highly active antiretroviral therapy regimens with or
      without didanosine.
AB  - BACKGROUND: In vitro phenotypic resistance studies suggest that the presence of
      the M184V mutation leads to a reduction in HIV-1 susceptibility to didanosine
      (ddl). The relevance of this to clinical outcomes remains unclear. In this study,
      we compared the virological response of ddl- and non-ddl-containing regimens in
      the presence or absence of the M184V mutation. METHODS: Data from an
      observational cohort study of all HIV-1 patients who had phenotypic resistance
      testing following the emergence of virological failure to an existing highly
      active antiretroviral therapy (HAART) regimen were analysed. A total of 586
      patients entered the study and were followed-up over 48 weeks; 281 (48%) were
      switched to ddl-containing HAART, of whom 105 had the M184V mutation at baseline.
      Virological efficacy of combination therapy was studied by reference to average
      area under the curve of viral load (VL) response and the proportion of patients
      attaining an undetectable VL (<400 copies/ml). Baseline characteristics and
      univariate analysis of changes in VL were compared using the Wilcoxon rank sum
      test. Multivariate analyses were performed using the Van Elteren test. Additional
      variables included the number of baseline nucleoside reverse transcriptase
      inhibitor mutations and the number of active antiretroviral drugs given to each
      group as compared by 'real phenotype' resistance test results. RESULTS: Amongst
      patients on ddl-containing HAART, median fold changes in phenotypic
      susceptibility to ddl were greater in patients with the M184V mutation (fold
      changes of 2.2 vs 1.2, P<0.001). Nonetheless, the median change in VL and
      percentage of patients attaining an undetectable VL were similar in those taking
      ddl, irrespective of whether the M184V mutation was present at baseline. In the
      group of patients with the M184V mutation at baseline, the virological outcome
      was significantly better in those treated with ddl-containing HAART than in those
      on HAART without ddl (P<0.05). CONCLUSIONS: While the M184V did increase the fold
      resistance of HIV to ddl, these changes appeared to be lower than the clinically
      relevant threshold for phenotypic resistance for this drug.

PMID- 15865232
TI  - Rare one and two amino acid inserts adjacent to codon 103 of the HIV-1 reverse
      transcriptase (RT) affect susceptibility to non-nucleoside RT inhibitors.
AB  - HIV-1 strains that possess a one or two amino acid insert between codons 102 and
      103 of the reverse transcriptase (RT) gene were identified in three HIV-1
      infected individuals. Each strain also had one or more known mutations associated
      with nucleoside RT inhibitors (NRTIs) and non-nucleoside RT inhibitors (NNRTIs).
      Recombinant viruses from these strains had reduced susceptibility to efavirenz
      and nevirapine, and homology modelling predicted a loss of binding contacts with
      efavirenz. Mutagenesis studies indicated that replication of insert-containing
      strains was dependent on RT gene mutations and polymorphisms that co-evolved with
      the insert. These results suggest that inserts in the NNRTI-binding pocket
      contribute to NNRTI resistance, but are tolerated only under specific genetic
      conditions.

PMID- 15865233
TI  - [Visual, auditory and somatosensory evoked potentials in normal pregnancies and
      pregnancies complicated by pre-eclampsia].
AB  - The influence of pregnancy induced hypertension (pre-eclampsia) on visual,
      auditory and somatosensory evoked potentials has been studied. The research was
      carried out on three groups of women: 63 pregnant women with hypertension, 45
      healthy pregnant women and 54 non-pregnant ones. Standard stimulation and
      recording technique of the evoked potentials was implemented. Comparing pregnant
      and non-pregnant women no statistically significant differences in the latencies,
      interlatencies and amplitudes of analyzed components of visual, auditory and
      somatosensory evoked potentials have been observed. In pre-eclamptic women the
      latency of the component P100 of the visual potentials, the latency N20 and the
      interlatency N13-N20 (CCT--central conduction time) of the somatosensory evoked
      potentials were prolonged. No statistically relevant differences concerning the
      latency or interlatency of the auditory evoked potentials in both groups of
      women: healthy pregnant and pre-eclamptic have been found. The amplitudes of the
      analyzed components of visual, auditory and somatosensory evoked potentials did
      not differ significantly in both groups. The positive correlation of the latency
      of component P100 of visual and N20 of somatosensory evoked potentials with MAP
      (mean arterial pressure) has been observed. In conclusion, pre-eclampsia causes
      abnormalities in visual and somatosensory evoked potentials. It is assumed that
      angiogenic changes in brain are the most probable cause of the abnormalities of
      visual and somatosensory evoked potentials. The practical aspect of
      neurophysiological research concerning the diagnosis of pre-eclampsia has been
      indicated.

PMID- 15865234
TI  - [Cytofluorimetric assay for evaluation of CD16 receptor expression and
      myeloperoxidase (MPO) activity of neutrophils in patients with psoriasis vulgaris
      treated with PUVA].
AB  - Early histological changes indicate the collecting of neutrophils in the stratum
      corneum, mainly in the acute psoriasis. Fc gammaRIIIB (CD16) is the specific
      functional neutrophilic receptor, which is responsible for phagocytosis.
      Myeloperoxidase (MPO) is granulocyte enzyme playing main role in metabolic
      activity of neutrophils. We have evaluated CD16 expression and MPO activity of
      polymorphonuclear granulocytes in the acute psoriasis vulgaris and the influence
      of photochemotherapy PUVA (psoralen plus ultraviolet light of A wavelength)
      treatment on these parameters. The expression of CD16 and MPO activity were
      significantly higher in neutrophils of patients after PUVA.

PMID- 15865235
TI  - [Antioxidative barrier activity assessment in gastro-esophageal reflux disease].
AB  - 92 patients with gastro-esophageal reflux disease (GERD) confirmed by 24-hour pH
      metry, upper gastrointestinal tract endoscopy, and X-ray barium scan were
      examined in this study. All patients were divided into 2 groups: first consisted
      of patients (51) with no signs of esophagitis and the second one (41) included
      individuals with gastro-oesophageal reflux complicated with inflammation.
      Inflammation of the mucosa was confirmed by pathological examination. In these
      patients superoxide dismuthase (SOD) and glutathione peroxidase (GP) activities
      were measured in serum and mucosal homogenates. Tests were performed before and 8
      weeks after treatment. Control group consisted of patients scheduled for elective
      inguinal hernia repair procedure. Serum SOD activity in oesophagitis patients was
      1173.7 U/gHb before the treatment, and 1401.7 U/gHb afterwards. These differences
      were statistically significant. Also differences in SOD serum activity in
      oesophagitis and non-oesophagitis patient groups were significant. Serum GP
      activity in oesophagitis patients was 11.17 U/gHb before and 25.12 U/gHb after
      treatment. The differences showed statistical significance. Measured activities
      did not reach the control values too. Serum SOD and GP activity was lower than
      those measured in tissue homogenates from corresponding patient groups. The
      significant role of antioxidative barrier in the development of GERD was
      emphasized in this study.

PMID- 15865236
TI  - [Diagnosis and treatment of zygomatic bone fractures].
AB  - Zygomatic bone fractures are the second most often injury of facial skeleton and
      sometimes cause diagnostic and treatment problems. Authors of this article
      present diagnostic and treatment methods applied in 165 patients (139 men, 22
      women, 4 children) treated in I Department of Maxillofacial Surgery in Zabrze, in
      year 1996-2000. Closed repositioning was performed in 70 patients with fractures
      with single bone fragment. In multiple fractures complicated with sight disorders
      (diplopia) and in case of old fractures, open repositioning and fixation using
      mini- and microplates was a method of choice. Achieved clinical and radiological
      results of treatment show that both close repositioning with single-toothed hook
      and open repositioning and fixation are effective methods of treatment. Early
      diagnosis and treatment of zygomatic fractures make treatment easier and prevent
      from vision and mastication complication.

PMID- 15865237
TI  - [Large artery wall properties in dialyse and renal transplant patients with
      normal blood pressure].
AB  - Structural and mechanical properties of the arterial wall are altered in patients
      with renal failure. Age and hypertension are known to affect the vessel wall
      structure. Aging process of arterial wall appears to be accelerated in patients
      with end-stage renal failure. The mechanisms responsible for reduced arterial
      compliance and distensibility in dialyse patients and renal transplant recipients
      without hypertension remain to be evaluated. 20 normotensive dialyse patients
      (D), 20 normotensive renal transplant recipients (T) and 20 healthy volunteers
      (N) matched for age, sex and blood pressure as controls were enrolled in to the
      study. Patients with cardiovascular risk factors and diabetes were excluded. The
      arterial blood pressure of all patients placed below 140/90 mmHg. The dialyse
      patients and renal transplant recipients were eligible for the study if the serum
      creatinine level was below 2 mg/dl. In all subjects, fasting concentrations of
      serum creatinine, total cholesterol, HDL-cholesterol, LDL-cholesterol, hemoglobin
      and glucose were determined at enrollment to the study. Long-term
      immunosuppression consisted of cyclosporine and prednisolone. Blood pressure was
      measured using an automatic sphygmomanometer (Criticon Dinamap model 1846 SX).
      Pulse wave velocity (PWV) was evaluated using non-invasive automatic Complior
      device. The vessel wall properties of the left common carotid artery were studied
      using multigate pulsed Doppler's system (Pie Medical Equipment BV Maastricht, The
      Netherlands). The frequency of transducer used was 7.5 MHz. With this non
      invasive method, the end-diastolic diameter (d) and the systolic increase of
      vessel diameter (distension delta d) were measured using ECG trigger. From these
      data relative systolic increase of vessel diameter (delta d/d) and arterial wall
      distensibility coefficient (DC) were calculated. Simultaneously with the
      ultrasound measurements at the left common carotid artery carotid pulse waveforms
      are recorded using applanation tonometry (Micro Tip Pulse Transducer, SPT 301 and
      Transducer Control Unit TCB-500, Millar Instruments, Houston, TX, USA). Systolic
      blood pressure (SBP) and central pulse pressure (CPP) were significantly higher
      in (T) than in (D) and (N) group respectively 139 +/- 18 mmHg and 58 +/- 16 mmHg
      vs 127 +/- 13 mmHg and 49 +/- 11 mmHg and 132 mmHg and 50 +/- 11 mmHg. The end
      diastolic diameter (d) did not change significantly between all groups. The
      systolic increase of vessel diameter (distension delta d) was significantly lower
      in patients group (D) and (T) respectively 461 +/- 33 microm and 501 +/- 34
      microm than in controls. Similar relative systolic increase of vessel diameter
      (delta d/d) was in these groups significantly lower than in healthy volunteers,
      respectively (D) 6.26 +/- 0.5%, (T) 6.91 +/- 0.4% vs (N) 9.14 +/- 0.4%. The
      distensibility coefficient were also significantly lower in (D) and (T) than in
      (N) groups respectively (D) 18.31 +/- 1.4 10(-3)/kPa and (T) 17.97 +/- 1.4 10(
      3)/kPa and (N) 24.3 +/- 0.5 10(-3)/kPa. PWV in both groups of patients was
      statistically significant higher than in control group correspondingly (D) 11.2
      +/- 1.02 m/s and (T) 12.8 +/- 1.12 m/s, (N) 9.5 +/- 0.88 m/s. There was
      significant correlation between the change of arterial DC, PWV and CPP in (T)
      group (n = 20; r = -0.42; p < 0.01 and n = 20; r = 0.47; p < 0.05). The arterial
      wall elastic properties in dialyse and renal recipients patients are decreased.
      End-stage renal disease accelerates arterial stiffening despite arteriosclerosis
      and hypertension. Renal transplantation do not reverse lost of elastic properties
      of arteries in end-stage renal insufficiency.

PMID- 15865238
TI  - [Comparison of diagnostic methods for Helicobacter pylori detection and
      identification of cagA gene in clinical specimens].
AB  - Helicobacter pylori (H. pylori) is the principal cause of peptic ulcer disease
      and important risk factor in gastric cancer. Gastric mucosal biopsy specimens
      taken from 110 patients were examined by polymerase chain reaction (PCR), culture
      and urease test. The ureA gene was detected in 52 out of 110 examined samples.
      The cagA gene was detected in 35 (67.3%) out of these 52 specimens (ureA+). This
      gene was presented in all of patients with stomach ulcer, in 75.0% of patients
      with duodenitis, 69.6% of patients with duodenal ulcer and 58.3% of patients with
      gastritis. H. pylori was detected by culture in 24 (25.3%) out of 95 samples.
      These results were confirmed by PCR. H. pylori was detected additionally in 20
      samples only by PCR. This bacterium was detected more frequently by PCR than by
      culture (46.3% vs 25.3%). Results obtained by using three methods: culture,
      urease test and PCR were concordant in 47.0% (39 out of 83 patients). In 16
      (19.3%) cases H. pylori was detected by two methods: urease test and PCR.
      Infection was detected only by PCR in 3 (3.6%) cases and in 25 cases (30.1%) only
      by urease test.

PMID- 15865239
TI  - [Prevalence of risk factors for atherosclerosis in participants of the Southern
      Poland Epidemiological Survey (SPES) with normal blood pressure].
AB  - Results of many studies indicate that cardiovascular diseases develop more often
      in subjects with blood pressure higher than optimal, but lower than the level, at
      which the diagnosis of arterial hypertension and implementation of therapy is
      justifiable. The aims of this study were the assessment of prevalence of risk
      factors for atherosclerosis among people with normal blood pressure in a
      population of Southern Poland (Southern Poland Epidemiological Survey--SPES), the
      quantitative evaluation of global risk for coronary events in relation to normal
      blood pressure classes, as well as the estimation of the size of subpopulation of
      subjects eligible for lipid-lowering treatment. A subpopulation of 15,484
      subjects without known hypertension and coronary heart disease with normal blood
      pressure measurements were chosen from a total of 50,111 participants of the SPES
      study. There were 5,304 men and 10,180 women, aged from 18 to 87 years. Optimal
      blood pressure (< 120/80) was observed in 24%, normal (120-129/80-84) in 40% and
      high normal (130-139/85-89) in 35% subjects. In both sexes, irrespective of blood
      pressure classes, the most prevalent risk factors were hypercholesterolemia,
      overweight/obesity and smoking. The prevalence of hypercholesterolemia (> 200
      mg/dl) increased along with blood pressure classes, and the proportion of
      subjects with cholesterol level > or = 240 was 1.5 times greater in those with
      high normal (21%), compared to those with optimal blood pressure (13%). The
      proportion of overweight/obesity was 1.5 times greater in subjects with high
      normal (50.5%) when compared to those with the optimal blood pressure (32.5%).
      The global risk for coronary events > 10% was more frequent in subjects with high
      normal blood pressure. Increase of the proportion of subjects eligible for lipid
      lowering therapy from near 0% in women with optimal to approximately 10% in men
      and 8% in women with high normal blood pressure. A rise of the normal blood
      pressure class is associated with a clear increase in the prevalence of
      atherosclerotic risk factors and the global coronary risk. An extended medical
      care should be considered to all subjects with high normal blood pressure and
      global risk greater than 10%, including lipid-lowering therapy in approximately
      10% of this subpopulation.

PMID- 15865240
TI  - [A comparison between prostatic volume measured during suprapubic ultrasonography
      (TAUS) and volume of the enucleated gland after open prostatectomy].
AB  - General practitioner very often uses transabdominal ultrasonograpy (TAUS) in
      order to measure prostatic volume. Using this method it is rather impossible to
      distinguish between tissue of benign prostatic hyperplasia (BPH) and prostatic
      tissue which forms so called surgical capsule of BPH. The aim of this study was a
      comparison of prostatic volume measured during suprapubic (transabdominal)
      ultrasonography and volume of the enucleated gland after open prostatectomy.
      Regarding the results authors created a nomogram based on TAUS measurement of the
      prostate which helps to predict the volume of BPH. They also stated that surgical
      capsule of the BPH makes about 1/3 of the whole volume of the prostate measured
      by TAUS.

PMID- 15865241
TI  - [Non-proliferative diabetic retinopathy and red blood cell aggregation].
AB  - The pathogenesis of diabetic retinopathy is not clear, but it is generally
      agreed, that in addition to vascular components hemorheological disturbances can
      play a role in the impairment of microvascular flow. The aim of this study was to
      correlate the severity of retinopathy in diabetic patients with red blood
      aggregation and some parameters of aggregation. The study was carried out on 52
      patients suffering from type 2 diabetes mellitus with non-proliferative
      retinopathy--25 men and 27 women (mean age 63.8 +/- 6.5 years) and 43 healthy--20
      men and 23 women (mean age 55.5 +/- 9.6 years). The fundus appearance of patients
      showed non-proliferative diabetic retinopathy. Red blood cell aggregation was
      determined by LORCA aggregometer. Aggregation index (AI), disaggregation shear
      rate (gamma(p)), time to the half of the disaggregation (t1/2), time constant of
      fast component in syllectogram (T1), time constant of slow component (T2) and
      amplitude (total extent of aggregation Am) were measured. In diabetics with non
      proliferative retinopathy we observed the increase of AI (66.5 +/- 7.2 vs 59.4 +/
      5.8; p < 0.001), decrease of Am (19.8 +/- 3.3 vs 21.2 +/- 2.7; p < 0.05),
      decrease of T1 (2.4 +/- 0.5 vs 2.75 +/- 0.42; p < 0.005), increase of T2 (27.6 +/
      4.7 vs 25.75 +/- 4.11; p < 0.05), decrease of t1/2 (1.98 +/- 0.72 vs 2.7 +/-
      0.77; p < 0.001) and increase of gamma(p) (215.6 +/- 23.3 vs 98.1 +/- 8.7; p <
      0.001). The parameters of erythrocytes aggregation were correlated with
      intensification of diabetic retinopathy symptoms. Our results show the importance
      of red blood cell aggregation parameters in the development of diabetic
      microangiopathy.

PMID- 15865242
TI  - [Serum intercellular adhesion molecule ICAM-1 concentration in interferon alpha
      treated patients with chronic viral C hepatitis].
AB  - Intercellular adhesion molecule is a protein regulating the inflammatory cells
      movement. An increase of ICAM-1 expression on hepatocytes and in serum has been
      observed in patients with chronic viral hepatitis. Interferon alpha treatment
      should lead to inflammatory response diminution and serum ICAM-1 concentration
      decrease. The aim of the study was the estimation of interferon alpha treatment
      influence on serum ICAM-1 concentration in patients with chronic viral C
      hepatitis. A group of 19 interferon alpha treated patients with chronic viral C
      hepatitis has been observed. ALT activity, the presence of HCV antibody and HCV
      RNAas well as histological examination has been estimated in every patient.
      Patients have got 144 doses of interferon alpha in a schedule 5 MU three times a
      week. After three months of treatment control estimations have been conducted for
      initial evoluation of treatment efficacy. Differences in ALT activity have been
      observed between I and III trials. ICAM-1 serum concentration has decreased
      significantly from 1322 to 369 pg/ml, and differences in ICAM-1 serum
      concentration have been observed in all trials. Estimation of serum ICAM-1
      concentration is an indirect parameter of attenuation of inflammatory reaction
      after interferon alpha treatment.

PMID- 15865243
TI  - [Diet as an important factor in the etiology of dental erosions].
AB  - A questionnaire study was carried out on 120 healthy subjects of both sexes. The
      age of the examined population was between 18-30 years. The subjects were divided
      into 2 groups comprising the same number of participants. The first and second
      group consisted of patients with and without enamel erosions respectively. The
      consumption of food like fruit juice, apples, citrus fruit, coca-cola, fizzy
      drinks and yoghurt and its influence on the frequency of enamel erosions were
      estimate. The analysis of the obtained results pointed to an existing
      relationship between diet and the existence of enamel erosions.

PMID- 15865244
TI  - [Chemokine RANTES activity and its potential role as a target for diagnosis and
      therapy].
AB  - This review introduces the chemokine RANTES, its role in the pathophysiology of
      disease and potential as a target for therapy. We present cell types which are
      the source of RANTES, specific chemokine receptors and the role of chemokine in
      regulating the movement of cells into the tissues during inflammation. Also
      opinions on mechanisms regulating the chemokine secretion by inflammatory
      cytokines were discussed. Chemokine RANTES is strongly induced by viral and
      bacterial infections and plays a role in allergic diseases, in asthma
      exacerbation, interstitial pneumonia, in allograft rejection and in cancers. This
      chemokine may represent target for diagnostic procedures and therapeutic
      intervention, and may be useful as a prognostic factor in cancer.

PMID- 15865245
TI  - [Role of inflammation and infection in the etiopathogenesis of atheromatosis-
      literature review].
AB  - The investigation of etiopathology of arteriosclerosis shows close relationship
      between inflammatory processes and evolution of sclerotic lesions. In many
      patients acute coronary syndromes are caused by the rupture of hemodynamically
      insignificant sclerotic lesion and consequently thrombosis of coronary artery.
      The reason of instability of sclerotic plaque may be on going inflammation inside
      it. This paper reviews literature on the subject of relationship of
      atheromatosis, inflammation and infection.

PMID- 15865246
TI  - [Vitamin D-resistant rickets].
AB  - Vitamin D-resistant rickets is a group of rare disease characterized by lack of
      reaction to vitamin D administered in doses sufficient to manage patients with
      rickets caused by vitamin D deficiency. These disorders result from disturbed
      metabolism and activity of vitamin D and/or disturbed phosphate metabolism. The
      most common vitamin D-resistant form of rickets is X-linked hypophosphatemic
      vitamin D-resistant rickets. Other forms are as the following: oncogenic
      hypophosphatemic osteomalacia, autosomal dominant hypophosphatemic rickets,
      hereditary hypophosphatemic rickets with hypercalciuria and pseudo-vitamin D
      deficient rickets type I and II.

PMID- 15865247
TI  - [The effects of chronic alcohol abuse on morphology and function of the
      gastrointestinal tract].
AB  - In this review we described the effects of chronic alcohol consumption upon the
      morphology and function of the gastrointestinal tract. Especially the attention
      was paid to the motility disorders, their pathogenesis and influence on symptoms
      occurrence and systemic consequences of alcoholism. Some recent publications,
      concerning the role of neuroendocrine small intestine system and ileum as an
      extrahepatic source of cytokine production in alcoholics, were reviewed.

PMID- 15865248
TI  - [Anthocyanins--"pigmental allies" of physicians].
AB  - Anthocyanins (2-phenyl-benzo-gamma-piron derivatives) are water-soluble plant
      pigments. Also they are components of human diet because of their common
      occurrence. They influence oxidative-reductive balance, modify inflammatory
      processes, regulate apoptosis, and furthermore can be benefcial in tumors
      treatment.

PMID- 15865249
TI  - [The mechanisms of inheritance of diabetes mellitus].
AB  - Diabetes is a genetic disease with a complicated mechanism of inheritance. The
      work presents contemporary views on genetic background of this disease. HLA
      phenotypes associated with type 1 diabetes as well as polygenic background of
      type 2 diabetes are discussed.

PMID- 15865250
TI  - [The role of tumor necrosis factor alpha receptors (TNF-alpha) in psoriasis and
      other skin disorders].
AB  - The paper presents data on the role of tumor necrosis factor alpha (TNF-alpha)
      receptors in skin disorders, especially in psoriasis. The usefulness of the
      measurement of these receptors as indicators of the disease activity has been
      discussed. New therapeutic options using anti-TNF-alpha molecules in dermatologic
      diseases are presented.

PMID- 15865251
TI  - [Neonatal intensive care unit--therapeutical success and what next?].
AB  - The increasing number of successfully treated newborns with disturbances of the
      adaptive period can measure effectiveness of neonatal intensive care units
      (NICU). The authors summarized some health problems of the former NICU patients.
      Central nervous system (CNS) of the premature, especially low (LBW) and very low
      birth weight (VLBW) infant, is in serious danger of improper development. The
      lack of neurological disturbances in early infancy does not exclude further
      pathological events and such patients require long-term observation and follow
      up. High-risk newborns are of great need of precise imaging and diagnosis of CNS,
      which should be performed before discharge. Early stimulation and developmental
      care program are the crucial points in the management of newborns with
      neurological abnormalities. Sensorial problems, especially the rate of vision and
      hearing impairments, can be significantly reduced when prophylactic schedule is
      applied. Both, etiological factors leading to respiratory insufficiency and some
      iatrogenic effects of the therapy, can influence respiratory system. Symptoms of
      different intensity--from sneezing caused by nasal mucous membrane edema to the
      severe forms of bronchopulmonary dysplasia (BPD)--may last for a long time and
      influence the child's general condition. The surgical closure of Botall's duct
      (persistent ductus arteriosus--PDA) usually normalizes the circulatory system. In
      serious heart defects or isolated shunt-type defects, the compensation of the
      circulatory system can easily be disturbed. Digestive tract problems belong to
      the two main groups: first--connected with the prematurity and immature
      interstitial functioning (necrotizing enterocolitis, digestive and absorption
      abnormalities, hepatic cholestasis), and second--caused by congenital defects
      requiring immediate surgical intervention. Despite different types of the
      diseases, the treatment and care have to be focused on necessary for the growing
      organism, optimal nutrients and calories uptake. Disturbances of social
      development, improper behavior, adaptation and emotional problems are mainly
      presented in VLBW patients and those with organic defects of the central nervous
      system.

PMID- 15865252
TI  - [Isolated splenic vein thrombosis].
AB  - We report the case of 61-year-old woman with isolated splenic vein thrombosis
      resulted from chronic pancreatitis. Left-sided portal hypertension secondary to
      splenic vein occlusion was responsible for development of the isolated gastric
      varices. The patient underwent prophylactic, successful splenectomy. Three months
      after splenectomy controlled endoscopy revealed disappearance of gastric varices.

PMID- 15865253
TI  - [Vasculitis with coagulopathic complications in the course of Coxsackie A9
      infection in a 13-year-old boy].
AB  - Viral infections are well known factors responsible for vasculitis. In our report
      we present the case of a 13-year-old boy with a history of life-threatening
      vasculitis complicated with coagulophathy. The only possible etiological agent
      was Coxsackie A9 infection. We were unable to find a report of a similar case in
      the available literature.

PMID- 15865254
TI  - [Cat-scratch disease of the parotid gland].
AB  - Cat-scratch disease is a mild disease associated with regional lymph node
      enlargement. We present a case of cat-scratch disease of the parotid gland in 10
      year-old girl. She presented with painful parotid mass, after unsuccessful
      treatment with antibiotics. Computed tomography showed tumour like lesions in
      parotid gland. Subtotal parotidectomy with facial nerve preservation was
      performed as neoplastic disease was suspected. Histopathology examination of the
      sample revealed typical changes for cat-scratch disease. History of continuous
      contacts with cats was confirmed by the parents. Cat-scratch disease should be
      taken into account in differential diagnosis of parotid masses, especially in
      children.

PMID- 15865255
TI  - [The Melkersson-Rosenthal syndrome as a problem of complex treatment].
AB  - The Melkersson-Rosenthal syndrome consists of triad of symptoms: recurrent oedema
      of lips, recurrent facial nerve paralysis and lingua plicata. Treatment is
      usually symptomatic and required cooperation of different specialists as:
      dermatologists, neurologists, dentists, laryngologists, surgeons. A rare case of
      Melkersson-Rosenthal syndrome in 49-year-old man was observed in the Clinic of
      Dermatology Silesian Medical Academy in Katowice.

PMID- 15865256
TI  - Nephrocalcinosis in a 2-month-old girl suffering from a mild variant of
      idiopathic infantile hypercalcemia.
AB  - Authors present a rare case of a mild variant of idiopathic infantile
      hypercalcemia (IIH), in a girl in whom nephrocalcinosis was diagnosed in the 8th
      week of life. Supplementation of vitamin D3 (400 i.u. per day) has been applied
      since the age of 3 weeks. The disease was recognised when exploring pyuria and
      lack of weight gain. Hypercalcemia was corrected by diet reduced in calcium, free
      of vitamin D3 and with high fluid intake. The first abdominal ultrasound after
      delivery was performed after 5 week vitamin D3 supplementation. It seems that if
      abdominal ultrasound scan had been done earlier it could have drawn our attention
      to the developing nephrocalcinosis and allowed us to start treatment more
      promptly.

PMID- 15865257
TI  - Subchronic toxicity of a fluoroalkylethanol mixture in rats.
AB  - The objective of this study was to evaluate the subchronic toxicity of a
      commercial fluoroalkylethanol mixture, which is an intermediate in the production
      of fluoroorganic compounds that are used as protectants and surfactants. The test
      substance was administered daily by gavage to Sprague-Dawley rats as a suspension
      in aqueous methylcellulose. The dosages were 0, 25, 100, or 250 mg kg(-1) day(
      1). A 1- and 3-month recovery period was included to evaluate the reversibility
      of toxic effects. No test substance-related mortality or neurotoxicity occurred.
      Body weights and/or nutritional parameters were significantly reduced at 100 and
      250 mg kg(-1) day(-1), and these effects were reversible. Broken and absent teeth
      were observed in rats dosed with 250 mg kg(-1) day(-1), and microscopic tooth
      lesions (ameloblast degeneration/disorganization) occurred at 100 and 250 mg kg(
      1) day(-1) and persisted with decreased severity throughout recovery. Decreased
      red cell mass parameters occurred at 90 days in the 250 mg kg(-1) day(-1) group,
      but red cell counts were normal thereafter during recovery. A persistent
      elevation of liver weights was seen in groups given > or =100 mg kg(-l) day(-1).
      The increased weights correlated with microscopic hepatocellular hypertrophy only
      in males and females administered 250 mg kg(-1) day(-1). Hepatic beta-oxidation
      was increased in a dose-dependent manner and persisted through 1 month of
      recovery at 250 mg kg(-1) day(-1). Increased kidney weights were observed at 25
      (females only), 100, and 250 mg kg(-1) day(-1). These elevated weights persisted
      in the high dose after recovery and correlated with microscopic tubular
      hypertrophy (males only). Thyroid follicular hypertrophy was present at 100 and
      250 mg kg(-1) day(-1) but was not present after recovery. Total fluorine in whole
      blood increased with continuous dosing and achieved steady state in approximately
      42 days. Both plasma and urine fluoride levels were elevated in a dose-dependent
      manner. Under the conditions of the study, the no-observed adverse effect level
      for this mixture was 25 mg kg(-1) day(-1) for subchronic toxicity.

PMID- 15865258
TI  - Evaluation of the reproductive and developmental toxicity of a fluoroalkylethanol
      mixture.
AB  - The objective of these studies was to evaluate the reproductive and developmental
      toxicity of a commercial fluoroalkylethanol mixture, which is an intermediate in
      the production of fluorotelomers. The test substance was administered daily by
      gavage to Sprague-Dawley rats as a suspension in 0.5% aqueous methylcellulose. In
      a one-generation reproductive toxicity study, rats (20 per sex per group) were
      given dosages of 0, 25, 100, or 250 mg kg(-1) day(-1) for a period of 74 days
      prior to cohabitation, and during mating, gestation, and lactation. Body weights,
      feed consumption, clinical signs, gross pathology, sperm parameters, estrous
      cyclicity, and reproductive performance were evaluated for the P1 generation. The
      F1 offspring were.evaluated during the lactation period for growth and survival
      and given a gross pathology examination at weaning. A subset of the offspring
      were retained; body weights, feed consumption, clinical signs, and age at onset
      of vaginal opening and preputial separation were evaluated, and gross pathology
      was performed on postnatal day 60. In the developmental toxicity study, groups of
      time-mated Sprague-Dawley female rats were given the test substance as a
      suspension in 0.5% aqueous methylcellulose at daily dosages of 0, 50, 200, or 500
      mg kg(-1) day(-1) by gavage on gestation days 6-20. During the in-life portion of
      the study, growth parameters and clinical observations were made. On gestation
      day 21, dams were euthanized, and the thoracic and abdominal viscera were
      examined. The uterine contents were removed and examined, and fetuses were
      evaluated for any alterations. In the reproduction study, litter size at birth,
      number of live pups per litter on day 0 and 4 of lactation, and pup weights
      during lactation were reduced in groups administered > or =100 mg kg(-1) day(-1).
      No other reproductive parameters were affected. There were no adverse
      reproductive effects observed at 25 mg kg(-1) day(-1). In the developmental
      toxicity study, reduced maternal body weight parameters, increased perineal fur
      staining, and increased fetal skeletal alterations were observed at 500 mg kg(-1)
      day(-1). There was no maternal or developmental toxicity at 50 or 200 mg kg(-1)
      day(-1). Under the conditions of the studies, the no-observed adverse effect
      levels for this mixture were 25 mg kg(-1) day(-1) for subchronic toxicity and
      reproductive parameters and 200 mg kg(-1) day(-1) for developmental toxicity end
      points. No functional reproductive or developmental effects were observed at dose
      levels that did not adversely affect adult animals.

PMID- 15865259
TI  - Effects of combined treatment with sildenafil and itraconazole on the
      cardiovascular system in telemetered conscious dogs.
AB  - Sildenafil, a potent PDE5 inhibitor, is widely prescribed as a treatment of
      erectile dysfunction. Itraconazole is an inhibitor of CYP3A4, a metabolic enzyme
      of sildenafil. In the current study, we investigated the effects of single
      treatment with sildenafil and combined treatment with sildenafil and itraconazole
      on blood pressure, heart rate, and QT interval in conscious beagle dogs. After a
      transmitter was implanted to beagle dogs for conscious state experiments, a
      single oral dose of sildenafil was administered to the beagle dogs at dose levels
      of 3, 15, and 30 mg/kg. Blood pressure, heart rate, and lead II ECG were measured
      prior to dosing and at 0.5, 1, 2, 4, 6, and 24 h postdosing. In the study of
      combined treatment with sildenafil and itraconazole, the 100 mg/kg dose of
      itraconazole was orally administered 1 h prior to oral administration of
      sildenafil. No changes in blood pressure were observed at any doses in animals
      receiving either single treatment with sildenafil or combined treatment with
      sildenafil and itraconazole. Increased heart rate from 0.5 h to 6 h postdosing
      and decreased QT interval were observed in animals receiving single treatment
      with sildenafil at 15 or 30 mg/kg. When 30 mg/kg of sildenafil was coadministered
      with 100 mg/kg of itraconazole, drug-related effects such as increased heart rate
      and decreased QT interval were significantly enhanced as compared to sildenafil
      alone administration at 6 h postadministration. These results demonstrated that
      increased heart rate and decreased QT interval, the adverse effects of
      sildenafil, were enhanced and prolonged when sildenafil was coadministered with
      itraconazole. Therefore, caution should be taken when sildenafil is
      coadministered with itraconazole, a CYP3A4 inhibitor, or when administered to
      elderly patients or patients with hepatic or renal impairment who cannot
      metabolize and excrete sildenafil normally.

PMID- 15865260
TI  - Brain lipid peroxidation and antioxidant status after acute methacrylonitrile
      intoxication.
AB  - The status of brain antioxidant enzymes and glutathione in methacrylonitrile
      (MeAN)-intoxicated Wistar rats was correlated with the levels of lipid
      peroxidation products. Optimum changes were observed 30 min and 60 min after oral
      administration of MeAN at dosages of 50 mg/kg body weight per day (0.25 LD50) and
      100 mg/kg body weight per day (0.5 LD50). An increase in lipid peroxidation
      products, decrease in the activity of antioxidant enzymes such as superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione
      reductase (GR), glutathione S-transferase (GST), and decrease in reduced
      glutathione (GSH) were observed. These studies suggest that the membrane lipid
      peroxidation observed in MeAN intoxication is related, in part, to a compromised
      antioxidant defense system.

PMID- 15865261
TI  - Subcellular distribution and protein binding of perfluorooctanoic acid in rat
      liver and kidney.
AB  - Perfluorooctanoic acid (PFOA) is an organic fluorochemical, and its elimination
      in rats is markedly sex-dependent. Liver and kidney are two primary tissues of
      distribution of PFOA in rats. In this study, the subcellular distribution of PFOA
      in male and female rat liver and kidney was examined. The results demonstrated
      that PFOA content in the liver cytosol of the female rat was significantly higher
      (49 +/- 6% of total radioactive residues, TRR) than in the male liver (26 +/- 5%
      TRR), whereas PFOA distribution in the heavier subcellular fractions, especially
      the nuclei and cell debris fraction, was marginally higher in male rat liver. In
      rat kidney, more than 70% of PFOA was distributed in the cytosolic fraction, with
      no significant difference between sexes. The degree of protein binding of PFOA in
      rat liver and kidney cytosol was analyzed by two different chromatographic
      methods. The percentage of protein-bound PFOA in the liver cytosol was found to
      be approximately 55% in both male and female rats. In contrast, significantly
      more PFOA was bound to cytosolic proteins in the kidney of male rats (42 +/- 6%
      TRR) than in females (17 +/- 5% TRR). Ligand blotting analysis revealed that
      multiple proteins from the liver cytosol, nuclei, and mitochondria fractions were
      capable of specific binding to PFOA.

PMID- 15865262
TI  - Protective effects of zinc on oxidative stress enzymes in liver of protein
      deficient rats.
AB  - Persons afflicted with protein malnutrition are generally deficient in a variety
      of essential micronutrients like zinc, copper, iron, and selenium, which in turn
      affects number of metabolic processes in the body. To evaluate the protective
      effects of zinc on the enzymes involved in oxidative stress induced in liver of
      protein-deficient rats, the current study was designed. Zinc sulfate at a dose
      level of 227 mg/L zinc in drinking water was administered to female Sprague
      Dawley normal control as well as protein-deficient rats for a total duration of 8
      weeks. The effects of zinc treatment in conditions of protein deficiency were
      studied on rat liver antioxidant enzymes, which included catalase, glutathione
      peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD),
      glutathione reduced (GSH), and glutathione-S-transferase (GST). Protein
      deficiency in normal rats resulted in a significant increase in hepatic
      activities of catalase, glutathione peroxidase, glutathione reductase, and
      glutathione-S-transferase and the levels of lipid peroxidation. A significant
      inhibition in the levels of reduced glutathione and the enzyme activity of
      superoxide dismutase has been observed after protein deficiency in normal rats.
      Interestingly, Zn treatment to protein-deficient animals lowered already raised
      activity catalase, glutathione peroxidase, and glutathione-S-transferase and
      levels of lipid peroxidation to significant levels when compared to protein
      deficient animals. Also, Zn treatment to the protein-deficient animals resulted
      in a significant elevation in the levels of GSH and SOD activity as compared to
      their respective controls, thereby indicating its effectiveness in regulating
      their levels in adverse conditions. It has also been observed that concentrations
      of zinc, copper, iron, and selenium were found to be decreased significantly in
      protein-deficient animals. However, the levels of these elements came back to
      within normal limits when zinc was administrated to protein-deficient rats. This
      study concludes that zinc has the potential to regulate the activities of
      oxidative stress enzymes as well as essential hepatic elements.

PMID- 15865263
TI  - Comparison between the genotoxicity of cis-Pt(ll) complex of 3-aminoflavone and
      cis-DDP in lymphocytes evaluated by the comet assay.
AB  - cis-bis(3-aminoflavone)dichloroplatinum(II) [cis-Pt(II) complex of 3
      aminoflavone] is an analog of cis-DDP characterized by low cytotoxicity and
      anticancer properties in vivo. In order to evaluate genotoxic properties of this
      chemical compound, the comet assay in human lymphocytes was used. The analysis of
      DNA damage after 1-h cell incubation with cis-Pt(II) complex of 3-aminoflavone
      and cis-DDP was carried out, and DNA repair kinetics were evaluated after 0.5-h,
      1-h, and 1.5-h postexposure incubation. It has been shown that cis-Pt(II) complex
      of 3-aminoflavone causes the increase in tail moments in comparison with cis-DDP.
      On the other hand, the decrease in these values caused by cis-DDP was connected
      mainly with the presence of DNA and DNA-protein crosslinks. The decrease in tail
      moments after cis-Pt(II) complex of 3-aminoflavone lymphocyte treatment was
      already observed after 0.5-h postexposure incubation, whereas in the variant with
      hydrogen peroxide application these values after cis-Pt(II) complex of 3
      aminoflavone addition were higher in comparison with cis-DDP. Results obtained on
      the basis of the comet assay could confirm the occurrence of DNA breaks and cross
      links induced by cis-Pt(II) complex of 3-aminoflavone.

PMID- 15865264
TI  - Gout induced by intoxication of sodium bicarbonate in Korean native broilers.
AB  - Gout is a metabolic disorder that results in hyperuricemia and the deposition of
      positively birefringent monosodium urate crystals in various parts of the body.
      Intoxication of sodium bicarbonate (SBC) for 35 days in Korean native broilers
      was investigated. Sixty birds, aged 2 weeks, divided into 5 groups were exposed
      to excess SBC: 2 g/L (group A), 7.5 g/L (group B), 20 g/L (group C), 40 g/L
      (group D). Toxicopathological examination of all exposed birds revealed the
      manifestation of visceral and articular gout in group C, while birds of group D
      showed acute kidney damage with manifestation of excessive visceral gout.
      Interestingly, few birds in group D also showed signs of rare condition of acute
      articular gout. Dose-dependent increments in erythrocytic count, hematocrit
      values, and hemoglobin levels of the exposed birds were observed. Hypernatremia,
      hyperuricemia, hypokalemia, and hypochloremia were common findings among exposed
      birds. Microscopic examination of birds that manifested visceral gout revealed
      significant urate deposit, tubular necrosis, and tophi formation in renal
      interstitium. These findings provide a pathophysiological link that SBC
      intoxication may support hyperuricemia, which is an independent risk factor for
      gout and other renal dysfunctions. Further study is required to delineate the
      effect of lowering uric acid on progression of gout and other renal diseases.

PMID- 15865265
TI  - Usefulness and accuracy of weekly point-prevalence surveys in active surveillance
      for healthcare-associated infections.

PMID- 15865266
TI  - Fine needle aspiration cytology without needle manipulation to reduce the risk of
      occupational infection in healthcare personnel.

PMID- 15865267
TI  - Methodologic issues of case-control studies: a review of established and newly
      recognized limitations.

PMID- 15865268
TI  - Impact of severity of illness bias and control group misclassification bias in
      case-control studies of antimicrobial-resistant organisms.
AB  - BACKGROUND: Case-control studies often analyze risk factors for antibiotic
      resistance. Recently published articles have illustrated that randomly selected
      control-patients may be preferable to those with the susceptible phenotype of the
      organism. A possible methodologic problem with randomly selected control-patients
      is potential bias due to control group misclassification. This occurs if some
      control-patients did not have clinical cultures performed and thus might have
      been unidentified case-patients. If this bias exists, these studies might be
      expected to report lower odds ratios (ORs) because control-patients would be more
      like case-patients. OBJECTIVE: To analyze potential biases that might arise due
      to control group misclassification and potentially larger selection biases that
      may be introduced if control-patients are required to have at least one clinical
      culture. PATIENTS: One hundred twenty case-patients, 770 control-patients in
      group 1, and 510 control-patients in group 2. METHODS: Two case-control studies.
      Case-patients had clinical cultures positive for imipenem-resistant Pseudomonas
      aeruginosa. The first group of control-patients were random. The second group of
      control-patients were identical to those in group 1 except being required to have
      at least one clinical culture. RESULTS: Univariate analyses showed higher ORs for
      case-patients versus control-patients in group 1 (imipenem [OR, 12.5],
      piperacillin-tazobactam [OR, 3.7], and vancomycin [OR, 4.7]) as compared with
      case-patients versus control-patients in group 2 (imipenem [OR, 8.0],
      piperacillin-tazobactam [OR, 2.5], and vancomycin [OR, 3.0]). CONCLUSION:
      Requiring control-patients to have at least one clinical culture introduces a
      selection bias likely because it eliminates patients with less severe illness.

PMID- 15865269
TI  - The case-case-control study design: addressing the limitations of risk factor
      studies for antimicrobial resistance.
AB  - OBJECTIVE: There are significant limitations of the standard case-control study
      design for identifying risk factors for resistant organisms. The objective of
      this study was to develop a study design to overcome these limitations. DESIGN:
      Theoretical analysis of different types of study designs that can be used in risk
      factor studies for resistant organisms. RESULTS: We developed the case-case
      control study design, which uses two separate case-control analyses within a
      single study. The first analysis compares patients infected with resistant
      bacteria (resistant cases) with control-patients without infection caused by the
      target organism, who are therefore representative of the source population; and
      the second analysis compares patients infected with the susceptible phenotype of
      the target organism (susceptible cases) with the same control-patients without
      infection caused by the target organism. These two analyses provide risk models
      for (1) isolation of the resistant phenotype of the target organism as compared
      with the source population and (2) isolation of the susceptible phenotype of the
      organism as compared with the source population. When these two risk models are
      compared and contrasted, risk factors specifically associated with isolation of
      the resistant phenotype can be identified. CONCLUSIONS: The case-case-control
      study design is an effective method for identifying risk factors for
      antimicrobial-resistant pathogens. Although the case-case-control study design
      has limitations, it is, in our opinion, more informative and less flawed than the
      standard case-control study design.

PMID- 15865270
TI  - Influence of matching for exposure time on estimates of attributable mortality
      caused by nosocomial bacteremia in critically ill patients.
AB  - OBJECTIVE: To evaluate the influence of matching on exposure time on estimates of
      attributable mortality of nosocomial bacteremia as assessed by matched cohort
      studies. DESIGN: Two retrospective, pairwise-matched (1:2) cohort studies.
      SETTING: A 54-bed intensive care unit (ICU) in a university hospital. PATIENTS:
      Patients with nosocomial Escherichia coli bacteremia (n = 68) and control
      patients without nosocomial bacteremia (n = 136 for each matched cohort study).
      INTERVENTION: In both matched cohort studies, the same set of bacteremic patients
      was matched with control-patients using the APACHE II system. In the first study,
      control-patients were required to have an ICU stay at least as long as the
      respective bacteremic patient prior to onset of bacteremia (matching on exposure
      time). In the second study, control-patients were required to have an ICU stay
      shorter than the stay prior to the development of bacteremia in the respective
      bacteremic patient (no matching on exposure time). RESULTS: For bacteremic
      patients, the mean ICU stay before onset of the bacteremia was 9 days (median, 6
      days). In the first matched cohort study, hospital mortality was not different
      between bacteremic patients and control-patients (44.1% vs 43.4%; P = .999). In
      the second study, mortality of bacteremic patients and control-patients was also
      not different (44.1% vs 47.8%; P = .657). Mortality rates between control groups
      were not different (43.4% vs 47.8%; P = .543). CONCLUSION: Matching or not
      matching on exposure time did not alter the estimate of attributable mortality
      for ICU patients with E. coli bacteremia.

PMID- 15865271
TI  - How outbreaks can contribute to prevention of nosocomial infection: analysis of
      1,022 outbreaks.
AB  - OBJECTIVE: To describe the epidemiology of nosocomial outbreaks published in the
      scientific literature. DESIGN: Descriptive information was obtained from a sample
      of 1,022 published nosocomial outbreaks from 1966 to 2002. METHODS: Published
      nosocomial outbreaks of the most important nosocomial pathogens were included in
      the database. A structured questionnaire was devised to extract information in a
      systematic manner on nosocomial outbreaks published in the literature. The
      following items were used: the reference, type of study (case reports or studies
      applying epidemiologic or fingerprinting methods), type of microorganism,
      setting, patients and personnel involved, type of infection, source of infection,
      mode of transmission, risk factors identified, and preventive measures applied.
      RESULTS: Bloodstream infection was the most frequently identified type of
      infection (37.0%), followed by gastrointestinal infection (28.5%) and pneumonia
      (22.9%). In 37% of the outbreaks, the authors were not able to identify the
      sources. The most frequent sources were patients (25.7%), followed by medical
      equipment or devices (11.9%), the environment (11.6%), and the staff (10.9%). The
      mode of transmission remained unclear in 28.3% of the outbreaks. Transmission was
      by contact in 45.3%, by invasive technique in 16.1%, and through the air in
      15.0%. The percentage of outbreaks investigated by case-control studies or cohort
      studies over the years was small (21% and 9%, respectively, for the whole time
      period). CONCLUSION: Outbreak reports in the literature are a valuable resource
      and should be used for educational purposes as well as for preparing outbreak
      investigations.

PMID- 15865272
TI  - Behavior of cross-sectional surveys in the hospital setting: a simulation model.
AB  - OBJECTIVE: To date, it has not been adequately proven whether the published
      formulas used to obtain incidence from the prevalence of nosocomial infections
      provide a good estimate of real incidence. With the hypothesis that within the
      hospital setting prevalence may be lower than incidence, the aim of this study
      was to analyze the behavior of point prevalence as it relates to cumulative
      incidence and duration of infection. DESIGN: Hospital simulation study. METHODS:
      By randomly selecting a sample of infected patients within a specific range of
      cumulative incidences and infection durations, we constructed a simulated
      hospital population, allowing us to estimate daily point prevalences and their
      maximum and minimum values. The association between the different components of
      stay and cumulative incidence was evaluated to obtain a more accurate estimate of
      incidence. RESULTS: Prevalence can be lower than, equal to, or higher than the
      corresponding incidence. For all incidence levels, prevalence was increasing with
      duration. Between 14 and 20 days of infection duration, prevalence was
      consistently lower than incidence. Prevalence duration of infection was
      approximately half the time of the total duration. CONCLUSIONS: The existing
      formulas relating incidence and prevalence can frequently be inadequate. Until a
      validated system for converting prevalence into incidence is available, we do not
      believe their use is appropriate.

PMID- 15865273
TI  - Assessment of the value of repeated point-prevalence surveys for analyzing the
      trend in nosocomial infections.
AB  - OBJECTIVE: To assess the value of repeated point-prevalence surveys in measuring
      the trend in nosocomial infections after adjustment for case mix. SETTING: A
      3,500-bed teaching facility composed of 4 acute care hospitals. METHODS: From May
      1992 to June 1996, eight point-prevalence surveys of nosocomial infections were
      performed in the hospitals using a sampling process. The trend of adjusted
      nosocomial infection rates was studied for the four surveys that collected data
      on indwelling catheters. Adjusted rates were calculated using a logistic
      regression model and a direct standardization method. RESULTS: From 1992 to 1996,
      a total of 20,238 patients were included in the 8 point-prevalence surveys. The
      nosocomial infection rate decreased from 8.6% in 1992 to 5% in 1996 (P < .001).
      The analysis of adjusted nosocomial infection rates included 9,600 patients. Four
      independent risk factors were identified: length of stay greater than 12 days,
      hospitalization in an intensive care unit, presence of an indwelling urinary
      catheter, and history of a surgical procedure. After adjustment for case mix, the
      nosocomial infection rate still showed a downward trend (from 7.2% in 1993 to
      5.1% in 1996; P = .02). CONCLUSION: Adjusted prevalence rates of nosocomial
      infections showed a significant downward trend during the period of this study.

PMID- 15865274
TI  - Inapparent outbreaks of ventilator-associated pneumonia: an ecologic analysis of
      prevention and cohort studies.
AB  - OBJECTIVE: To compare ventilator-associated pneumonia (VAP) rates and patterns of
      isolates across studies of antibiotic and non-antibiotic methods for preventing
      VAP. DESIGN: With the use of 42 cohort study groups as the reference standard,
      the prevalence of VAP was modeled in two linear regressions: one with the control
      groups and the other with the intervention groups of 96 VAP prevention studies.
      The proportion of patients admitted with trauma and the VAP diagnostic criteria
      were used as ecologic correlates. Also, the patterns of pathogenic isolates were
      available for 117 groups. RESULTS: In the first regression model, the VAP rates
      for the control groups of antibiotic-based prevention studies were at least 18
      (CI95, 12 to 24) per 100 patients higher than those in the cohort study groups (P
      < .001). By contrast, comparisons of cohort study groups with all other control
      and intervention groups in the first and second regression models yielded
      differences that were less than 6 per 100 and not significant (P > .05). For
      control groups with VAP rates greater than 35%, the patterns of VAP isolates,
      such as the proportion of Staphylococcus aureus, more closely resembled those in
      the corresponding intervention groups than in the cohort groups. CONCLUSIONS: The
      rates of VAP in the control groups of the antibiotic prevention studies were
      significantly higher than expected and the patterns of pathogenic isolates were
      unusual. These observations suggest that inapparent outbreaks of VAP occurred in
      these studies. The possibility remains that antibiotic-based VAP prevention
      presents a major cross-infection hazard.

PMID- 15865275
TI  - Endotoxin-like reactions with intravenous gentamicin: results from
      pharmacovigilance tools under investigation.
AB  - OBJECTIVE: To apply two data mining algorithms (DMAs) to Food and Drug
      Administration (FDA) Adverse Event Reporting System (AERS) reports that involved
      endotoxin-like reactions with intravenous gentamicin to determine whether a
      signal of disproportionate reporting of these events would have been generated
      concurrently with surveillance based on clinical observation. DESIGN: Multi-item
      gamma-Poisson shrinker (MGPS) and proportional reporting ratios (PRRs) were used.
      Data used for data mining consisted of an extract of the FDA AERS database.
      Previously published details of clusters of endotoxin-like reactions to
      intravenous gentamicin were used to select adverse events for data mining.
      RESULTS: The first signal of disproportionate reporting with any relevant event
      occurred in 1998, the year in which the outbreak was identified and evaluated by
      the Centers for Disease Control and Prevention and the FDA. In 1997, there were
      only 6 reports of rigors in the AERS; this jumped to 68 in 1998. In 1998, a
      signal was generated for endotoxic shock with PRRs but not with MGPS, based on
      one case. CONCLUSIONS: The two DMAs generated signals concurrently with the
      influx of reports. It would have been difficult for safety reviewers to ignore an
      increase in rigors by traditional methods of safety surveillance; therefore, DMAs
      might not have had a great deal to offer in this instance. If data mining were
      considered as a second-line defense to diligent clinical observations under
      similar circumstances, simple disproportionality methods such as PRRs might be
      more useful than DMAs such as MGPS when commonly cited thresholds are used.

PMID- 15865276
TI  - Antimicrobial consumption data from pharmacy and nursing records: how good are
      they?
AB  - OBJECTIVE: To determine whether randomly selected intravenous (IV) antimicrobial
      doses dispensed from an inpatient pharmacy were administered. DESIGN: This was a
      prospective, cross-sectional study in which dose administration was confirmed by
      direct observation and by assessment of the medication administration record
      (MAR). A retrospective analysis of the return rate of unused IV antimicrobial
      doses was performed subsequently. SETTING: Medical and surgical intensive care
      units (ICUs) and non-ICUs of a 550-bed urban public teaching hospital.
      PARTICIPANTS: Hospitalized patients with an order in the pharmacy database for an
      IV antimicrobial during 9 non-consecutive weekdays in June 1999. RESULTS: Of 397
      doses, 221 (55.7%) assessed by bedside observation and 238 (59.9%) assessed by
      MAR review were classified as administered; 139 doses (35.0%) were dispensed but
      changes in the drug order or the patient's status prevented their administration.
      In the subsequent assessment, of 745 IV antimicrobial doses dispensed during 24
      hours, 322 (43.2%) were returned to the pharmacy unused; 423 (56.8%) of the doses
      consistent with our prior observations-were presumably administered. CONCLUSIONS:
      Because computerized pharmacy data may overestimate actual antimicrobial
      consumption, such data should be validated when used in studies of hospital
      antimicrobial use. Dispense-return analysis offers a simple validation method.

PMID- 15865277
TI  - Isolation of infectious cystic fibrosis patients: results of a systematic review.
AB  - OBJECTIVE: Respiratory tract infections significantly contribute to morbidity and
      mortality among cystic fibrosis (CF) patients. Therefore, pathogen transmission
      needs to be prevented. There are several guidelines for the care of CF patients,
      but no transparent systematic literature review has been published. METHODS: We
      conducted a systematic literature review (January 1966 to September 2004) dealing
      with segregation of CF patients colonized with Burkholderia cepacia species,
      Pandoraea species, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, or
      Alcaligenes species. Quality of studies was evaluated by taking patient
      population size, existence of control-patients, patient randomization, diagnostic
      approach, and bacteria typing methods into account. RESULTS: One hundred ninety
      nine studies were found. Evidence and quality of 102 publications were evaluated.
      In 99 publications, recommendations concerning segregation measures for
      infectious CF patients were determined including a total of 11,576 patients. No
      randomized, controlled trials had been conducted. Fifty of 56 authors strongly
      recommended isolation of CF patients infected with B. cepacia or Pandoraea
      species. In 31 of 39 studies, interpatient spread of Pseudomonas aeruginosa was
      documented or had been brought to an end by isolation of patients. Only five
      studies had addressed S. maltophilia or Alcaligenes species. CONCLUSIONS:
      Patients colonized with B. cepacia or Pandoraea species are to be separated from
      noncolonized patients in single rooms. Patients harboring multidrug-resistant
      Pseudomonas aeruginosa, S. maltophilia, or Alcaligenes species may not share a
      room with immunocompromised patients, in intensive care units, or with other CF
      patients anywhere in the hospital.

PMID- 15865278
TI  - Evaluation of policies regarding physicians infected with blood-borne pathogens.
AB  - OBJECTIVE: Formulating an effective approach to preventing surgeon-to-patient
      transmission of blood-borne pathogens has been controversial. The objective of
      our study was to evaluate current community hospital policies, if any, regarding
      restrictions on surgeons (general surgeons and obstetricians and gynecologists)
      infected with blood-borne pathogens operating on patients. DESIGN: A survey on
      hospital policies regarding surgeons infected with blood-borne pathogens was sent
      to infection control officers at Northern California community hospitals (n =
      113). RESULTS: Forty-five hospitals responded to the survey. Of these, only 6
      (13.3%) had a policy. Of the 39 (86.7%) that did not have a policy, only 3
      hospitals were planning on implementing one. CONCLUSIONS: Many community
      hospitals are uninterested in instituting a policy regarding the practice of
      surgeons infected with blood-borne pathogens. Possible reasons include the lack
      of concern on the individual level, difficulty in defining exposure-prone
      procedures, and the nature of the relationship between medical staff and
      community hospitals.

PMID- 15865279
TI  - Estimation of the cumulative incidence of hospital-acquired bacteremia from
      prevalence data: a formula.
AB  - We evaluated the validity of the formula of Rhame and Sudderth to estimate the
      cumulative incidence of nosocomial bacteremia from prevalence studies. The
      observed cumulative incidence was threefold higher than the calculated cumulative
      incidence. We do not recommend converting prevalence into incidence data for
      nosocomial bloodstream infections.

PMID- 15865280
TI  - Medical errors detected and corrected by a pediatric infectious diseases
      consultation service.
AB  - Errors occur frequently in healthcare and can adversely affect outcomes. This
      prospective study demonstrates that pediatric consultants can detect a broad
      range of errors in the course of routine work. Many of these errors have the
      potential to cause harm and can be corrected by the intervention of an infectious
      diseases consultant.

PMID- 15865281
TI  - Prerequisite programs and food hygiene in hospitals: food safety knowledge and
      practices of food service staff in Ankara, Turkey.
AB  - Our objective was to determine food safety practices related to prerequisite
      program implementation in hospital food services in Turkey. Staff often lack
      basic food hygiene knowledge. Problems of implementing HACCP and prerequisite
      programs in hospitals include lack of food hygiene management training, lack of
      financial resources, and inadequate equipment and environment.

PMID- 15865282
TI  - Nuclear matrix proteins and hereditary diseases.
AB  - The review summarizes literature data on alterations of structure or expression
      of different nuclear matrix proteins in hereditary syndromes. From the point of
      view of involvement of nuclear matrix proteins in etiology and pathogenesis of
      the disease hereditary pathologies can be classified in pathologies with
      pathogenesis associated with defects of nuclear matrix proteins and pathologies
      associated to changes of the nuclear matrix protein spectrum. The first group
      includes laminopathies, hereditary diseases with abnormal nuclear-matrix
      associated proteins and triplet extension diseases associated with accumulation
      of abnormal proteins in the nuclear matrix. Laminopathies are hereditary diseases
      coupled to structural defects of the nuclear lamina. These diseases include Emery
      Dreifuss muscular dystrophy, limb girdle muscular dystrophy, dilated
      cardiomyopathy (DCM) with conduction system disease, familial partial
      lipodystrophy (FPLD), autosomal recessive axonal neuropathy (Charcot-Marie-Tooth
      disorder type 2, CMT2), mandibuloacral dysplasia (MAD), Hutchison Gilford
      Progeria syndrome (HGS), Greenberg Skeletal Dysplasia, and Pelger-Huet anomaly
      (PHA). Most of them are due to mutations in the lamin A/C gene, one - to
      mutations in emerin gene, some are associated with mutations in Lamin B receptor
      gene. In Werner's, Bloom's, Cockayne's syndromes, Fanconi anemia, multiple
      carboxylase deficiency mutations in nuclear matrix protein or enzyme gene lead to
      deficient DNA repair, abnormal regulation of cell growth and differentiation or
      other specific metabolic functions. Proteins with a long polyglutamic tract
      synthesized in the cells of patients with dentato-rubral and pallido-luysian
      atrophy, myotonic dystrophy and Huntington disease interfere with transcription
      on the nuclear matrix. Down's syndrome is a representative of the group of
      diseases with altered nuclear matrix protein spectrum.

PMID- 15865283
TI  - [Transcription and mRNA splicing of the human lactoferrin gene controlled by the
      regulatory region of the bovine alphaS1 casein gene in the mammary gland of
      transgenic mice and in mouse embryonic stem cells].
AB  - The regulatory region of the bovine alphaS1 casein gene was used to obtain two
      genetic constructs for expression of human lactoferrin in the mammary gland of
      transgenic animals. Several transfected mouse embryonic stem cell (ESC) lines and
      primary transgenic mice were generated with these constructs. Recombinant
      lactoferrin was not detected in milk of transgenic mice by Western blotting.
      However, a recombinant transcript was found in RNAs isolated from mammary glands
      of transgenic females during lactation and from transfected ESC lines.

PMID- 15865284
TI  - [Unequal genetic exchange in Escherichia coli tandem duplications may represent a
      special pathway of homologous recombination].
AB  - Heterozygous tandem duplications that appear in Escherichia coli conjugation
      matings segregate different types of haploid and diploid recombinants because of
      unequal crossing over between sister chromosomes. As shown previously, the
      frequency of segregants in the extended duplication D104 (approximately 150 kb or
      more than 3 min of the genetic map) heterozygous for E. coli deo-operon genes
      (deoA deoB::Tn5/deoC deoD) is not decreased in strains with defective RecBCD and
      RecF recombination pathways. Analysis of a shorter duplication of this type
      (approximately 46 kb) showed that the frequency of segregants in the strain recBC
      sbcBC recF was similar to that in a strain with undamaged system of
      recombination. Thus, genetic exchange between direct DNA repeats in tandem
      duplications may follow a special pathway of homologous recombination, which is
      independent of the recBC and recF genes.

PMID- 15865285
TI  - [Genetics of the cell cycle: adaptive modification of the cycB2g mutation
      expression in dividing cells of Drosophila melanogaster].
AB  - The effect of mutation CycB2g on mitosis in neural ganglia and imaginal disks was
      studied in third-instar larvae of Drosophila melanogaster. Chromosome
      condensation and segregation were shown to be impaired in dividing cells of
      mutant larvae. During the three-year period of maintenance of the mutation in
      heterozygote, frequencies of some defects decreased via cellular adaptive
      modification.

PMID- 15865287
TI  - [The effect of population density on the elimination dynamics of a recessive
      lethal mutation from experimental populations].
AB  - Dynamics of the elimination of the temperature-sensitive lethal mutation
      l(2)M167DTS from experimental populations of Drosophila melanogaster under
      permissive conditions (25 degrees C) was studied. We have shown a rapid
      elimination of the mutation from the populations, selection for fitness of
      heterozygous individuals, association of the selection with high larval density
      and with the direction of the cross that had produced the founder males of the
      l(2)M167DTS/+ population, and the effect of relative competitive ability of
      l(2)M167DTS/+ males on the efficiency of the mutation introduction. Modification
      systems were shown be involved in fitness selection under conditions of high
      larval density.

PMID- 15865286
TI  - [Polymorphism of mitochondrial DNA and infection with symbiotic cytoplasmic
      bacterium Wolbachia pipientis in mosquitoes of the Culex pipiens complex from
      Russia].
AB  - A total of 208 mosquitoes of the Culex pipiens complex from 15 basement and
      terrestrial populations collected in different regions of the European part of
      Russia and Siberia were examined by genetic methods. Among these, two major
      mitotypes, M and P, were identified. These mitotypes differed by six
      substitutions in the 246-bp mitochondrial DNA cytochrome oxidase I gene fragment
      examined. Urban basement mosquito ecotype C. pipiens (form molestus) were
      characterized by the presence of mitotype M and infection with the endosymbiotic
      bacteria of the genus Wolbachia. Mosquitoes of the C. pipiens complex inhabiting
      opened biotopes harbored mitotype P, or its variety, mitotype P1, and were not
      infected with Wolbachia. Thus, in natural conditions marked linkage
      disequilibrium between cytoplasmic elements, mitochondrial DNA and Wolbachia, can
      be observed. Similarity of mitotypes in form molestus mosquito from different
      geographical localities favors the hypothesis on the common ancestry of urban
      mosquitoes.

PMID- 15865288
TI  - [Flax species polymorphism for isozyme and metabolic markers].
AB  - Genetic diversity of flax isozyme patterns of 6-phosphogluconate dehydrogenase,
      glutamate-oxaloacetate transaminase, and cytochrome-c-oxidase in leaves, as well
      as the level and the relative amounts of fatty acids in seed oil were studied in
      flax species. The isozyme loci examined were found to be polymorphic. It was
      shown that each of the flax species studied was characterized by strictly defined
      amounts and proportions of fatty acids, i.e., the fatty acid composition of the
      seed oil may be used as a species diagnostic trait. Our results suggest that all
      of the flax species studied have the same ancestor. Linum grandiflorum was shown
      to be a phylogenetic branch split at an early stage of the flax evolution.

PMID- 15865289
TI  - [Identification and mapping of polymorphic RAPD markers of pea (Pisum sativum L.)
      genome].
AB  - Various pea cultivars, lines, and mutants were studied by the RAPD method.
      Polymorphic fragments characteristic of certain pea genotypes and which can be
      used for identifying genotypes were detected. Inheritance of some polymorphic
      RAPD fragments was studied. Mendelian inheritance of these fragments was shown.
      By analyzing the data obtained in studies of RAPD polymorphism, genetic distances
      between different pea cultivars, lines, and mutants were calculated and a
      genealogic dendogram showing a varying extent of differences between RAPD
      patterns was constructed. Ten new RAPD markers linked to various pea genes were
      detected. Genetic distances between RAPD markers and genes to which they are
      linked were calculated, and the respective disposition of RAPD markers on
      chromosomes was established.

PMID- 15865290
TI  - [Study of mitochondrial genomes of allopllasmic recombinant wheat lines
      constructed on the basis of barley-wheat hybrids Hordeum geniculatum all. (= H.
      marinum subsp. gussoneanum) (2n = 28) x x Triticum aestivum L. (2n = 42) with
      using of RELP and PCR analyses].
AB  - Using RELP analysis with three probes homologous to specific regions of
      mitochondrial DNA genes and PCR analysis of the mitochondrial recombining-repeat
      sequence 18S/5S region of cereals, five alloplasmic wheat lines of different
      origin and fertility expression were studied. These lines are self-pollinated
      progeny of BC1-BC4 generations of barley-wheat hybrids Hordeum geniculatum All.
      (2n = 28) x Triticum aestivum L. (2n = 42). It was found that recombinant
      alloplasmic lines characterized by partial fertility contain either maternal
      (barley) DNA fragments or maternal and paternal (wheat) DNA fragments
      simultaneously (heteroplasmy). In lines with stable expression of self-fertility,
      fragments of only paternal mitochondrial DNA were detected. It is assumed that in
      alloplasmic lines, there is the interrelation between the presence of definite
      fragments of the mitochondrial genome belonging to either parental type and
      fertility expression.

PMID- 15865291
TI  - [Genetic variation and differentiation of Abies alba Mill. populations from
      Ukrainian Carpathians].
AB  - Using electrophoretic analysis of 11 enzyme systems, we studied the genetic
      structure and differentiation of eight natural populations of silver fir Abies
      alba Mill. in the Ukrainian Carpathians. Of 24 isozyme loci identified, 66.8%
      proved to be polymorphic. The mean numbers of alleles and genotypes per locus in
      the populations were respectively 3.1 and 4.5. Each A. alba tree was on average
      heterozygous at 15.9% of genes. In six populations, the genotypic distribution
      for all of the loci examined corresponded to Hardy-Weinberg proportions. The
      populations studied had low levels of subdivision (F(ST) = 0.018; GST = 0.019)
      and differentiation. Nei's genetic distances between the A. alba populations in
      the region ranged from 0.002 to 0.009, being on average 0.006.

PMID- 15865292
TI  - [Chromosomal polymorphism of the unique Baikal deep-water population of Sergentia
      flavodentata (Diptera, Chironomidae) from the region of hydrothermal venting].
AB  - The subject of this study is chromosomal polymorphism of a population of Baikal
      endemic species Sergentia flavodentata (Diptera, Chironomidae) from the Frolikh
      Bay region of hydrothermal venting at a depth of 420-430 m. In 35-67% of larvae,
      six heterozygous inversions were found to be preserved for 13 years (materials of
      1991, 1994, 1996, 1999, 2003). The number of zygotic combinations reached 14; 0.5
      0.7 inversions per individual was observed. It is suggested that stable
      chromosomal polymorphism characteristic of this species is nonrandom, being a
      mechanism of the population adaptation to the specific conditions of hydrothermal
      venting community based on bacterial biochemosynthesis.

PMID- 15865293
TI  - [Macrogeographic genetic variability in the gastropod mollusk Littorina sitkana
      from the northwest Pacific].
AB  - Variation at four highly polymorphic allozyme loci (inorganic pyrophosphatase,
      peptidase, and two esterase loci) was examined in 25 settlements of the marine
      snail Littorina sitkana (Mollusca, Gastropoda). The sampling localities covered a
      wide part of the species range: from the Peter the Great Bay (the Sea of Japan)
      at the southwest to the Mednyi Island (Commander Islands) at the northeast. Like
      other littorines lacking the pelagic stage, L. sitkana was characterized by
      significant genetic differentiation (G(ST) for the pooled sample was 0.310).
      Cluster analysis and nonmetric multidimensional scaling conducted on a matrix of
      pairwise genetic distances between all of the settlements studied revealed four
      genetically different groups: southern Primorye, northern Prymorye, Sakhalin, and
      Kuril-Commanders. The population-genetic structure of the L. sitkana settlements
      is close to that described by the isolation-by-distance and stepping-stone
      models: the geographic and the genetic distances between the most settlements
      examined are distinctly correlated.

PMID- 15865294
TI  - [The role of nucleotide context in the induction of mutations in human
      mitochondrial DNA genes].
AB  - Based on the mutations distribution patterns in the mitochondrial DNA (mtDNA)
      genes, context analysis of the regions, including mutable positions characterized
      by the appearance of more than two parallel mutations, was performed. It was
      demonstrated that the mechanism of dislocation mutagenesis, leading to the
      appearance of mismatches within the frameshift regions of either primer or
      template mtDNA chains during replication, accounts for the induction of 21% of
      unstable positions in the mtDNA genes. Context analysis showed that pyrimidine
      bases in the positions +1 and +2 (gYRNS, gYY, and gR consensuses, where g is
      mutable position) had the highest influence on the induction of mutations in G
      positions of the mtDNA genes. The highest effect on the mutagenesis in T
      positions was excreted by the bases in the positions -1 and +1 (RyT and tA
      consensuses, where t is mutable position). In general, these data point to the
      prevalence of the context-dependant mechanisms of the mutations induction in
      human mitochondrial genome.

PMID- 15865295
TI  - [Comparison of the rates of aneuploidy occurrence in quiescent and dividing cells
      of humans exposed to adverse environmental factors].
AB  - Fluorescence in situ hybridization (FISH) was used to compare aneuploidy rates in
      four autosomes and two sex chromosomes in interphase nuclei of noncultivated
      (quiescent) and cultivated (induced to divide with phytohemagglutinin (PHA))
      leukocytes in people engaged in nuclear-chemical industry and in a control group
      of people not exposed to mutagenic factors occupationally or at home. The overall
      rates of numerical chromosome aberrations for all of the six chromosomes studied
      showed little difference, although a higher rate of loss of the X- and Y
      chromosomes was observed in the exposed group. In individuals exposed to several
      adverse environmental factors, the overall rate of numerical chromosome
      aberrations in cultivated cells after at least one DNA replication cycle exceeded
      that in noncultivated cells by 52% (P = 0.01), whereas only a trend for its
      increase was observed in the control group (23%, P = 0.25). Thus, the effect of
      adverse environmental factors in humans caused more than a twofold increase in
      the difference between the rates of aneuploid cells in cultivated and non
      cultivated leukocytes in the exposed group as compared to control. It is
      conjectured that cell division is accompanied by the expression of potential
      damage of mitotic chromatid segregation apparatus accumulated in vivo. These
      defects, realized during cell division, bring about numerical chromosome
      aberrations.

PMID- 15865296
TI  - [Cytogenetic analysis of human spermatozoa using intracytoplasmic sperm injection
      into mouse oocytes].
AB  - The chromosome complement of human spermatozoa has been analyzed after their
      intracytoplasmic injection into unfertilized mouse oocytes. A total of 427
      metaphase plates have been obtained, including 176 metaphase plates from
      spermatozoa with normal head morphology (108 and 68 spermatozoa from patients
      with normal (the control group) and abnormal spermogram parameters,
      respectively), and 251 metaphase plates from spermatozoa with abnormal heads (76,
      91, 67, and 17 spermatozoa with large, amorphous, elongated, and round heads,
      respectively). The frequency of chromosome abnormalities in the control group is
      26.1%, with hyperploidy, hypoploidy, and structural aberrations accounting for
      7.4, 12.3, and 6.4% of the abnormalities, respectively. In none of the groups did
      the ratio between the numbers of X- and Y-bearing spermatozoa significantly
      differ from 1 : 1. The diploidy frequency was significantly higher in spermatozoa
      with large and amorphous heads compared to the control group (2.36, 3.29, and 0%,
      respectively). None of the groups of spermatozoa differed from the control group
      with respect to the frequency of structural aberrations. The type of the abnormal
      head morphology has been found to be correlated with the sperm chromosome
      complement.

PMID- 15865297
TI  - [Prevalence of widespread BRCA1 gene mutations in patients with familial breast
      cancer from St. Petersburg].
AB  - Ten variants different from the canonical nucleotide sequence (GenBank, U14680)
      has been identified when studying the mutation spectrum in gene BRCA1. Six of
      them (5382insC, 2963del10, 3819de15, 3875del4, 2274insA, and R1203X) cause
      premature termination of protein synthesis, thus predisposing to breast cancer. A
      missense mutation E1250K is presumed to be a factor of predisposition to cancer.
      We classified three variants of nucleotide sequence found in some patients as DNA
      polymorphisms S694S, L771L, and E1038G. The 5382insC and 3819de15 mutations have
      been detected in four and two families, respectively. Five of the mutations
      detected have not been found in Russia before. However, all mutations except for
      2963del10 have been found in other populations of the world, which indicates
      their long evolutionary history. Two mutations found in patients from St.
      Petersburg (5382insC and 3875de14) have also been found in oncological patients
      from other regions of the Russian Federation.

PMID- 15865298
TI  - [Recurrent model of the dependence of a recessive lethal mutation on fitness
      components and its solution].
AB  - Experimental modeling and subsequent analysis of microevolutionary processes
      often involves estimation of fitness components, such as male mating
      competitiveness, female fecundity, progeny viability, meiotic drive upon the
      formation of sexual products, and so on. In this connection, we have developed a
      new method for estimating the relationship among fitness components and their
      effect on selection on frequencies of the mutant individuals in several
      generations, which can be applied to the case of rapid elimination of a lethal
      mutation from the population. The method of estimating unknown fitness components
      is based on the known estimates of other components and a relationship among the
      known and unknown components calculated from the frequency dynamics. Using the
      new method, a biological explanation of non-uniqueness of the admissible
      solutions. The method employs analysis of the form of the admissible solution
      region (at preset confidence intervals for the observed frequencies) in the space
      of the possible values.

PMID- 15865299
TI  - [Effect of the hereditary characteristics of male blue foxes Alopex lagopus L. on
      the sex ratio of their offspring].
AB  - Family analysis of a commercial population of the blue fox (the Pushkinskoe
      Breeding Fur Farm, Moscow oblast) with respect to secondary sex ratio has been
      performed. The offspring of each individual male or female involved in crossing
      between 1984 and 1988 was analyzed. The study of all families formed by every
      male and every female has made it possible to determine a group of "outstanding"
      fathers (23 out of 287 males), whose offspring was predominantly male (62.1% of
      the offspring were males, versus 53.9% in the total population). The results of
      subsequent detailed study on the pedigrees of male blue foxes in whose offspring
      the sex ratio significantly deviates from 1:1 indicate that this character is
      transmitted from fathers to sons without the deterioration of other commercially
      valuable characters. It is presumed that the significant deviation of sex ratio
      from 1:1 in the offspring of some male blue foxes is determined by genetic
      factors.

PMID- 15865300
TI  - [Identification of the gene whose mutation leads to hypocotyl tropism in
      Arabidopsis thaliana].
AB  - Genetic and molecular analysis of a mutant of Arabidopsis thaliana with bended
      hypocotyl from a previously obtained collection of insertion mutants is
      presented. The examined mutation was shown to be recessive and based on a single
      insertion of pLD3 vector T-region into the A. thaliana genome. Computer-aided
      analysis of a DNA region adjacent to the left border of the insertion revealed a
      putative site of T-DNA insertion, the At1g15760 gene from 609-bp chromosome 1
      represented by a single exon.

PMID- 15865301
TI  - The SUCOZOMA program: results and challenges.
AB  - The research program Sustainable Coastal Zone Management (SUCOZOMA), which was
      started in 1996 by the Swedish Foundation of Strategic Environmental Research,
      was motivated by the recognition of increasingly severe global, regional and
      national coastal problems. The program approached the complex issues of coastal
      eutrophication, fishing practices, and overexploited coastal resources, with a
      concerted effort involving multidisciplinarity, stakeholder cooperation, and a
      focus on the problems perceived as most serious by the public and decision
      makers. As the program was concluded in 2004 it had resulted in the completion or
      near-completion of 22 doctoral dissertations and approximately one hundred
      publications. More than 40 scientists were involved in the program. Goteborg
      University was the host university, but important research teams have also been
      located at Stockholm University, the Beijer Institute, and the Kristineberg
      Marine Research Station of the Royal Swedish Academy of Sciences, and within the
      National Board of Fisheries. During the program, networks of stakeholders were
      established and SUCOZOMA had contributed to numerous political and administrative
      processes relevant for integrated coastal zone management (ICZM). SUCOZOMA
      program results can be grouped into different categories. Many of the projects in
      the two phases of the program produced results which can be defined as technical
      or practical and available for direct implementation in, e.g. mussel cultivation,
      restoration and safeguarding of spawning areas, seal-safe fishing gear or
      sustainable fishing of underexploited species. Other results can be characterized
      as policy oriented, and the impact of these can only be fairly evaluated as new
      policies are put into effect. SUCOZOMA resulted in important new knowledge
      regarding coastal science and management, but also concerning the organization
      required to conduct an end-user oriented multidisciplinary program effectively.

PMID- 15865302
TI  - Interdisciplinary conflict analysis and conflict mitigation in local resource
      management.
AB  - Within the Swedish research program SUCOZOMA (Sustainable Coastal Zone
      Management) several conflict studies have been carried out. Whereas the detailed
      results of these studies are published separately, this paper reviews important
      results from conflict research in combination with a summarizing and generalizing
      discussion of approaches and main results of SUCOZOMA's resource and conflicts
      studies. After an analysis of interdisciplinary and theoretical research about
      environmental and resource use conflicts, the methodology used in SUCOZOMA is
      presented, a combined stakeholder and conflict analysis. It can be summarized in
      four main points: i) to map the stakeholders and their interests; i) to analyse
      the conflicts; iii) to develop methods for conflict mitigation and cooperation
      with stakeholders; iv) to integrate these components in a system for the
      management of natural resources. Exemplary case studies of resource use conflicts
      have been carried out at the Swedish west and east coast including coastal
      fishery, mussel culture, coastal planning and specific conflicts such as between
      species protection (seals) and coastal fishery. Researchers are involved as
      experts and as conflicting parties, and the role of scientists as stakeholders
      deserves special attention in conflict research. Conflict management is not only
      for the solution of present conflicts, but part of integrated resource management
      systems where knowledge transfer, institutional development, collective learning
      of scientific, political and administrative actors, and cooperation between
      scientists and resource users can occur.

PMID- 15865303
TI  - Public participation in municipal planning as a tool for coastal management: case
      studies from western Sweden.
AB  - This article analyses four main models of participation in Swedish natural
      resource management and assesses strengths and weaknesses of one model
      (participation in physical/spatial planning) based on empirical studies of
      coastal resource conflicts in two Swedish west coast municipalities. In
      comparison to other administrative and planning procedures, physical planning
      offers possibilities to coordinate land and water management across sectors and
      resources and to broaden stakeholder participation. Local influence on coastal
      management increases with participation beyond the statutory minimum
      requirements, although management frameworks and practice of participation need
      to be developed further. Besides educating professionals and experimenting with
      combinations of existing procedures, in the long run an adaptation of legislation
      to the requirements of integrated and sustainable coastal management will be
      necessary.

PMID- 15865304
TI  - A net loss: policy instruments for commercial cod fishing in Sweden.
AB  - This paper describes the overfishing of the seas, in particular for cod in
      Sweden. It discusses policy instruments such as individual quotas, labelling and
      marine reserves. A tentative conclusion is that something needs to be done to the
      very structure of the policy instruments used. Information on stock depletion is
      available but goes unheeded and is counteracted by fishermen who want to fish
      more and who are routinely supported by "the political establishment" who appear
      to be most concerned about (short-term) employment. The whole debate is taking
      place before the eyes of a general public that does not care sufficiently and
      difficult international bureaucracy. In this situation, the most important
      changes may be to strengthen both the rights and the duties of the fishermen. The
      integrity of fish stocks must be given absolute priority, but it is also
      important to motivate the fishermen with a greater stake and interest in the
      stock by giving them quotas that have, as far as possible, the characteristics of
      property.

PMID- 15865305
TI  - Local fisheries management at the Swedish coast: biological and social
      preconditions.
AB  - Most of the Swedish coastal fisheries are not sustainable from either a social,
      economic or ecological point of view. We propose the introduction of local
      fisheries management (LFM) as a tool for restructuring the present large-scale
      management system in order to achieve sustainability. To implement LFM two
      questions need to be answered: How to distribute the resource fish among
      different resource user groups? How to restructure present fisheries management
      to meet the criteria of sustainability? Starting from these questions we describe
      possible forms of LFM for Swedish coastal fishery supported by recent research.
      The biological and social preconditions for restructuring fisheries management
      are derived from an analysis of the ecological and managerial situation in
      Swedish fishery. Three types of LFM--owner based, user based, and community based
      management--are analyzed with regard to the tasks to be carried outin LFM, the
      roles of management groups, and the definition and optimal size of management
      areas.

PMID- 15865306
TI  - Fishermen's interests and cooperation: preconditions for joint management of
      Swedish coastal fisheries.
AB  - The participation of fishermen in fisheries management is discussed with varying
      ideas under the notions of "co-management", "participatory management" or "local
      management". Empirical studies within Swedish fishery have thrown new light on
      the preconditions for fishermen's participation in fisheries management. Among
      the important factors influencing failure or success are the two which we discuss
      here: the question of articulation, organization and representation of interests
      of fishermen and the question of trust between the groups that are usually
      cooperating in resource management, fishermen, governmental administrators and
      researchers. The research summarized has addressed the interests of fishermen
      with regard to resource management, local fisheries management, and participation
      of fishermen. The overarching question connecting the three themes is: How can
      the interests of fishermen be represented better within fisheries management?
      Interests and trust, "soft facts", can be as important for the success or failure
      of fisheries management and participation as can "hard facts" such as ownership
      rights, quantity and quality of resources or monetary value of resources.

PMID- 15865307
TI  - Genetic population structure of fishes: implications for coastal zone management.
AB  - The pattern for distribution of genetic variation within and between populations
      is referred to as the genetic population structure of the species. To avoid
      depletion of genetic resources sustainable management should be based on
      knowledge of this structure. We discuss key aspects of genetic population
      structure in the context of identifying biological units for fisheries
      management, suggesting three basic types of structuring: distinct populations;
      continuous change; and no differentiation. The type of structure determines how
      units for genetically sustainable management are to be identified. We also review
      what is currently known regarding the genetic population structure of fishes
      exploited in the Swedish part of the Baltic Sea, and conclude that sufficient
      genetic information is lacking for most of the species. This is a serious
      problem, particularly considering that populations of several commercially
      exploited fishes are declining and some exhibit recruitment problems. For six
      species, Atlantic herring, Atlantic salmon, brown trout, European eel, turbot,
      and pike, sufficient genetic data are available to provide at least basic
      information on genetic structure and genetic units for biologically sustainable
      use. Current management practices do not sufficiently consider these data.

PMID- 15865308
TI  - Management of pikeperch migrating over management areas in a Baltic archipelago
      area.
AB  - Pikeperch Sander lucioperca (L.) were tagged in an area where ten small
      independent management units regulate fisheries, in order to analyze the
      relevance of migrations for the management. A total of 465 fishes were tagged in
      connection with the spawning migration. The number of recaptures was 96. The
      distribution of recaptures between areas and that of total catches, estimated
      from questionnaire to housholds and, individuals in the survey area, were
      correlated. The comparison of tagging and recapture dates showed that the same
      pikeperch migrated to the spawning areas at the same time in two subsequent
      years, indicating the existence of individual spawning behavior. A modified
      yield/recruit-model demonstrated that in situations where the dispersal area of a
      pikeperch stock overlaps with several management areas, the risk of overfishing
      is very high. Management of this kind of fisheries needs cooperation between
      units as well as sound data on the movements of pikeperch to define the effects
      of fishing regulations.

PMID- 15865309
TI  - Boating and navigation activities influence the recruitment of fish in a Baltic
      Sea archipelago area.
AB  - We studied the effects of boating and navigation activities on the recruitment of
      coastal fish in the Stockholm archipelago in the NW Baltic proper. The impacts
      were quantified by sampling metamorphosed young-of-the-year (Y-O-Y) fish in
      inlets adjacent to i) routes for medium-sized passenger ferries; ii) berths
      (small marinas) with small boats; and iii) references. Species with high
      preference for vegetation were negatively influenced by boating and navigation
      activities and species with low preference positively influenced. Pike (Esox
      lucius) Y-O-Y were significantly more abundant in reference areas, while bleak
      (Alburnus alburnus) were more abundant in dredged marinas. No statistically
      significant patterns were identified for perch (Perca fluviatilis) although there
      was a trend of low abundance along ferry routes. Many species of nearshore fishes
      are dependent on submerged vegetation as spawning and larval substrate,
      structural refuge and feeding habitat. Our results suggest that the negative
      effects from boating and navigation activities on the coverage and height of
      vegetation, especially on species of Chara and Potamogeton spp., may contribute
      to changes in the Y-O-Y fish community.

PMID- 15865310
TI  - Improving marine water quality by mussel farming: a profitable solution for
      Swedish society.
AB  - Eutrophication of coastal waters is a serious environmental problem with high
      costs for society globally. In eastern Skagerrak, reductions in eutrophication
      are planned through reduction of nitrogen inputs, but it is unclear how this can
      be achieved. One possible method is the cultivation of filter-feeding organisms,
      such as blue mussels, which remove nitrogen while generating seafood, fodder and
      agricultural fertilizer, thus recycling nutrients from sea to land. The expected
      effect of mussel farming on nitrogen cycling was modeled for the Gullmar Fjord on
      the Swedish west coast and it is shown that the net transport of nitrogen (sum of
      dissolved and particulate) at the fjord mouth was reduced by 20%. Existing
      commercial mussel farms already perform this service for free, but the benefits
      to society could be far greater. We suggest that rather than paying mussel
      farmers for their work that nutrient trading systems are introduced to improve
      coastal waters. In this context an alternative to nitrogen reduction in the
      sewage treatment plant in Lysekil community through mussel farming is presented.
      Accumulation of bio-toxins has been identified as the largest impediment to
      further expansion of commercial mussel farming in Sweden, but the problem seems
      to be manageable through new techniques and management strategies. On the basis
      of existing and potential regulations and payments, possible win-win solutions
      are suggested.

PMID- 15865311
TI  - Shellfish and public health: a Swedish perspective.
AB  - Bivalves are ancient animals that feed by filtering large volumes of water. In
      this way, phytoplankton, bacteria and viruses from the water column are greatly
      concentrated in the mussels. The hazards associated with the consumption of
      mussels are thus dependent on the occurrence and composition of toxic algae and
      human microbial pathogens in the areas where shellfish are grown. Diarrheic
      shellfish toxins have occurred regularly in Sweden during the past 27 years.
      Peaks of toxins in mussels are mostly recorded from October to December, but the
      pattern can differ significantly due to location and year, making it hard to
      predict toxin levels in mussels. With an expansion of aquaculture and a
      subsequent increase in seafood consumption, better risk management is needed to
      minimize the effects on humans of algal toxins and human pathogens. New control
      strategies that have to be implemented are: i) proper site selection of culture
      installations; ii) regular and cost-efficient monitoring of algae, bacteria and
      viruses; iii) new indicators for fecal contamination, suitable for the specific
      locations where shellfish grow; iv) rapid dissemination of information to the
      industry and public, including risk assessment and advice on how to cope with the
      situation.

PMID- 15865312
TI  - Tracing the influence of sewage nitrogen in a coastal ecosystem using stable
      nitrogen isotopes.
AB  - This paper reviews the use of stable nitrogen isotopes (delta15N) to delineate
      the influence of sewage nitrogen (N) in coastal ecosystems, drawing extensively
      on the case of Himmerfjarden, a Baltic Sea bay that receives 15N-enriched
      tertiary treated sewage that is discharged mainly as dissolved inorganic N (DIN).
      Gradients of delta15N in macroalgae (Fucus vesiculosus) and surface sediments
      traced sewage-derived N to 24 km from the outfall but elevated delta15N values (>
      7 per thousand) indicated that the sewage influence was most pronounced within 10
      km. Comparison of macroalgal delta15N values before and after enhanced tertiary
      treatment showed a decrease in the spatial impact of sewage N from about 24 km to
      12 km from the outfall and a decrease to more marine delta15N values in more
      recent growth tissues. Sedimentary delta15N records showed that sewage has had a
      dominant influence on organic matter production in the bay with dramatic
      increases in sedimentary delta15N during the years of maximum sewage N loads. In
      cases where sewage N introduces a distinct isotopic signature into a system and
      where it has had a dominant influence on organic matter production, delta15N
      values in biota and sediments can be used to trace the spatial and temporal
      influence of sewage N in aquatic ecosystems.

PMID- 15865313
TI  - Obtaining access to coastal areas for large-scale mussel farming: obstacles and
      possibilities.
AB  - Eutrophication in the coastal waters of the northern part of the Swedish west
      coast is causing structural and functional changes to the coastal ecosystems.
      Large-scale mussel farming is proposed in the Program of Measures, required by
      the EU Water Framework Directive to reduce the nutrients in the coastal water and
      improve water quality over a transition period of 10-20 years. Ownership, land
      parcelling, conflicts of interest, and the protection of coastal water are
      obstructing accessibility to suitable water areas for the establishment of mussel
      farming plants. This paper studies the obstacles and possibilities in the
      relevant laws and legal regulations governing the accessibility to coastal waters
      for large-scale mussel farming. Alternative ways to solve the problem are shown
      and discussed, within the framework of the Planning and Building Act, the
      Environmental Code and the laws concerning land-parceling and property. It is
      shown that the Planning and Building Act, when used in a proper manner, can
      provide useful instruments for society to gain access to coastal water for mussel
      farming plants with the purpose of improving the ecological status of the water.

PMID- 15865314
TI  - Adaptive coastal planning and the European Union's water framework directive: a
      Swedish perspective.
AB  - The implementation of the EU Water Framework Directive and the achievement of its
      water quality objectives will to a large degree depend on scientific knowledge
      about the sources and status of water resources and the effects of mitigative
      measures. Coastal waters will be of central interest, since the management of
      whole river basins may be affected if coastal water status is not satisfactory.
      The Water Directive's general directions on what information the water
      authorities need and on suitable methods for obtaining such information leave it
      to the Member states to decide on more precise instructions. Improved legal
      mechanisms are needed to assist and guide the managers and scientists charged
      with implementing the directive and achieving its water quality objectives,
      particularly when faced with insufficient information, flawed knowledge, or
      changed circumstances. We assess progress in the current process of implementing
      the Water Directive in Sweden, focussing on coastal waters, and on general
      problems arising using this type of legal technique.

PMID- 15865315
TI  - The rule of sustainability and planning adaptivity.
AB  - This article confronts present main stream planning approaches against the
      perspective of ecological sustainability, as relevant for Rule of Law countries
      and based on a modern environmental law approach. It discusses the setting and
      implementation of environmental goals against the general experience of massive
      implementation deficits regarding environmental policies all over the world. In
      this confrontation, environmental planning, with at least some principles picked
      up from New Zealand's Resource Management Act, and much more taken from modern
      environmental law theory on legal operationalisation, is compared to adaptive
      management approaches which also allow for modifying the environment related goal
      if implementation fails or seems very difficult. The concept of adaptive
      environmental planning (AEP) is suggested as a possible road to choose for
      planning for sustainability, while maximizing development within the framework
      legally defined by means of environmental limits. This article presents five
      criteria, all of which must be met by AEP planning. One of these relates to a
      planning hierarchy which, among other things, leads to the conclusion that
      coastal planning, if it is intended to aim at sustainability, can not be dealt
      with in isolation, although such planning might have to meet very complex
      problems at the regional level.

PMID- 15865316
TI  - Economic valuation for sustainable development in the Swedish coastal zone.
AB  - The Swedish coastal zone is a scene of conflicting interests about various goods
      and services provided by nature. Open-access conditions and the public nature of
      many services increase the difficulty in resolving these conflicts.
      "Sustainability" is a vague but widely accepted guideline for finding reasonable
      trade-offs between different interests. The UN view of sustainable development
      suggests that coastal zone management should aim at a sustainable ecological,
      economic, and social-cultural development. Looking closer at economic
      sustainability, it is observed that economic analyses about whether changes in
      society imply a gain or a loss should take into account the economic value of the
      environment. Methods used for making such economic valuation in the context of
      the Swedish coastal zone are briefly reviewed. It is noted that the property
      rights context matters for the results of a valuation study. This general
      background is followed by a concise presentation of the design and results of
      four valuation studies on Swedish coastal zone issues. One study is on the
      economic value of an improved bathing water quality in the Stockholm archipelago.
      The other studies are a travel cost study about the economic value of improved
      recreational fisheries in the Stockholm archipelago, a replacement cost study on
      the value of restoring habitats for sea trout, and a choice experiment study on
      the economic value of improved water quality along the Swedish westcoast.

PMID- 15865317
TI  - Knowledge transfer between researchers and practitioners in SUCOZOMA.
AB  - A primary aim of the SUCOZOMA research program has been the transfer of knowledge
      from the scientific community to research users. This paper describes the
      intentions and ambitions regarding knowledge transfer within the program,
      reflecting the aim of its financier, the Swedish Foundation of Strategic
      Environmental Research, but also a general trend within research policy. The
      study investigates the areas in which SUCOZOMA has actively tried to transfer
      knowledge, reaching out to management and different practitioners. Many examples
      of communication and participation of research users in the program are
      described. The paper also identifies the bottlenecks and limits to communication.

PMID- 15865318
TI  - Caenorhabditis elegans opens up new insights into circadian clock mechanisms.
AB  - The roundworm, Caenorhabditis elegans, is known to carry homologues of clock
      genes such as per (=period) and tim (=timeless), which constitute the core of the
      circadian clock in Drosophila and mammals: lin-42 and tim-1. Analyses using
      WormBase (C. elegans gene database) have identified with relatively high identity
      analogous of the clock genes recognized in Drosophila and mammals, with the
      notable exception of cry (=cryptochrome), which is lacking in C. elegans. All of
      these C. elegans cognates of the clock genes appear to belong to members of the
      PAS-superfamily and to participate in development or responsiveness to the
      environment but apparently are not involved in the C. elegans circadian clock.
      Nevertheless, C. elegans exhibits convincing circadian rhythms in locomotor
      behavior in the adult stage and in resistance to hyperosmotic stress in starved
      larvae (L1) after hatching, indicating that it has a circadian clock with a core
      design entirely different from that of Drosophila and mammals. Here two
      possibilities are considered. First, the core of the C. elegans circadian clock
      includes transcriptional/translational feedback loops between genes and their
      protein products that are entirely different from those of Drosophila and
      mammals. Second, a more basic principle such as homeostasis governs the circadian
      cellular physiology, and was established primarily to minimize the accumulation
      of DNA damage in response to an environment cycling at 24 h intervals.

PMID- 15865319
TI  - Circadian rhythms in sports performance--an update.
AB  - We discuss current knowledge on the description, impact, and underlying causes of
      circadian rhythmicity in sports performance. We argue that there is a wealth of
      information from both applied and experimental work, which, when considered
      together, suggests that sports performance is affected by time of day in normal
      entrained conditions and that the variation has at least some input from
      endogenous mechanisms. Nevertheless, precise information on the relative
      importance of endogenous and exogenous factors is lacking. No single study can
      answer both the applied and basic research questions that are relevant to this
      topic, but an appropriate mixture of real-world research on rhythm disturbances
      and tightly controlled experiments involving forced desynchronization protocols
      is needed. Important issues, which should be considered by any chronobiologist
      interested in sports and exercise, include how representative the study sample
      and the selected performance tests are, test-retest reliability, as well as
      overall design of the experiment.

PMID- 15865320
TI  - Altitudinal variation in the circadian rhythm of oviposition in Drosophila
      ananassae.
AB  - The effect of altitude on four basic properties of the pacemaker controlling the
      circadian rhythm of oviposition in two strains of Drosophila ananassae was
      determined. The high altitude (HA) strain from Badrinath (5123 m above sea level)
      had a low amplitude peak in the forenoon while the low altitude (LA) strain from
      Firozpur (179 m a.s.l.) had a high amplitude peak after the lights-off of LD
      12:12 cycles. Free running periods in continuous darkness were about 22.6 and
      27.4 h in the HA and LA strains, respectively. The light pulse phase response
      curve (PRC) for the HA strain showed a low amplitude and a dead zone of 8h; the
      ratio for the advance to delay region (A/D) was less than 1, while the PRC for
      the LA strain had a high amplitude, which was devoid of a dead zone and showed a
      ratio of A/D > 1. The magnitude of the delay phase shifts at CT 18 evoked by
      light pulses of 1 h duration, but varying light intensity was significantly
      different in the HA and LA strain, which suggests that the photic sensitivity of
      the clock photoreceptors mediating the phase shifts had been affected by the
      altitude.

PMID- 15865321
TI  - Seasonality and seasons out of time--the thermoregulatory effects of light
      interference.
AB  - The change in photoperiod is the main environmental cue for seasonal function of
      the reproductive, thermoregulatory, and immune systems in rodents existing
      outside of the tropics. In Israel, the social vole Microtus socialis breeds
      mainly under short photoperiod (SP) conditions. Previous studies showed that
      exposing voles to light interference (LI) in the field during the winter resulted
      in death. The aim of the current study was to determine the thermoregulatory
      response of SP-acclimated voles to LI. Therefore, heat production (VO2) at
      different ambient temperatures (Ta) and nonshivering thermogenesis (NST) were
      measured. Results show that LI of 15 min every 4h during the dark period
      significantly (p < 0.02) decreased VO2 at Ta = 15 degrees C and significantly (p
      < 0.05) decreased NST-capacity. These results can at least partly explain why LI
      voles died during the winter under field conditions, through eliminating winter
      acclimatization of the thermoregulatory system, or what is considered as "seasons
      out of time."

PMID- 15865322
TI  - Influence of light intensity on plasma melatonin and locomotor activity rhythms
      in tench.
AB  - Melatonin production by the pineal organ is influenced by light intensity, as has
      been described in most vertebrate species, in which melatonin is considered a
      synchronizer of circadian rhythms. In tench, strict nocturnal activity rhythms
      have been described, although the role of melatonin has not been clarified. In
      this study we investigated daily activity and melatonin rhythms under 12:12 light
      dark (LD) conditions with two different light intensities (58.6 and 1091
      microW/cm2), and the effect of I h broad spectrum white light pulses of different
      intensities (3.3, 5.3, 10.5, 1091.4 microW/cm2) applied at middarkness (MD) on
      nocturnal circulating melatonin. The results showed that plasma melatonin in
      tench under LD 12:12 and high light conditions displayed rhythmic variation,
      where values at MD (255.8 +/- 65.9 pg/ml) were higher than at midlight (ML) (70.7
      +/- 31.9 pg/ml). Such a difference between MD and ML values was reduced in
      animals exposed to LD 12: 12 and low light intensity. The application of 1 h
      light pulses at MD lowered plasma melatonin to 111.6 +/- 3.2 pg/ml (in the 3.3
      10.5 microW/cm2 range) and to 61.8 +/- 18.3 pg/ml (with the 1091.4 microW/cm2
      light pulse) and totally suppressed nocturnal locomotor activity. These results
      show that melatonin rhythms persisted in tench exposed to low light intensity
      although the amplitude of the rhythm is affected. In addition, it was observed
      that light pulses applied at MD affected plasma melatonin content and locomotor
      activity. Such a low threshold suggests that the melatonin system is capable of
      transducing light even under dim conditions, which may be used by this nocturnal
      fish to synchronize to weak night light signals (e.g., moonlight cycles).

PMID- 15865323
TI  - Daily variations in colchicine-induced apoptosis in duodenal crypts.
AB  - Apoptotic cell death can be induced by several agents, among them colchicine, a
      microtubule disrupting-drug that affects continuously renewing cell populations,
      such as the intestinal crypt enterocytes. The objectives of this investigation
      were (1) to confirm in vivo colchicines-inductive effect and (2) to determine the
      existence of 24 h variations in the crypt enterocytes apoptotic indices. The
      study was done on C3H/S male adult mice housed under standardized conditions.
      Starting at midnight until the end of a circadian period, subgroups of mice were
      sacrificed after having been injected with colchicine or saline i.p. 4h
      beforehand. Duodenal samples were processed for hematoxylin-eosin staining and
      TUNEL technique. In order to score the number of apoptosis, the longitudinal
      sections of the crypts were divided into three regions comprised, respectively,
      of tiers 1-4, 5-12, and 13-20, proceeding from the bottom to the top of the
      crypt. Values of each lot were expressed as mean +/- SEM. A highly significant
      statistical difference in apoptotic indices was found for colchicine-treated
      animals. The 24 h curve for colchicine-induced apoptosis displayed qualitative
      and quantitative differences compared to other inducer agents. Highest apoptotic
      indices were found in the deepest crypt regions. Daily variations were observed
      in all the crypt sectors of the colchicine-treated animals and in tiers 5-12 of
      the saline controls. The present work demonstrates that the colchicine
      cytotoxicity due to its apoptotic-inducing effect depends on the dosing time
      during the 24 h in this mouse strain.

PMID- 15865324
TI  - The effect of traumatic brain injury on the timing of sleep.
AB  - While there have been single case reports of the development of circadian rhythm
      sleep disorders, most commonly delayed sleep phase syndrome following traumatic
      brain injury (TBI), to our knowledge there have been no group investigations of
      changes to sleep timing in this population. The aim of the present study was to
      investigate sleep timing following TBI using the dim light melatonin onset (DLMO)
      as a marker of circadian phase and the Morningness-Eveningness Questionnaire
      (MEQ) as a measure of sleep-wake behavior. A sleep-wake diary was also completed.
      It was hypothesized that the timing of DLMO would be delayed and that there would
      be a greater tendency toward eveningness on the MEQ in a post-acute TBI group
      (n=10) compared to a gender and age matched control group. Participants were
      recruited at routine outpatient review appointments (TBI) and from the general
      population (control) as part of a larger study. They attended the sleep
      laboratory where questionnaires were completed, some retrospectively, and saliva
      melatonin samples were collected half-hourly according to a standard protocol.
      The results show that the TBI and control groups reported similar habitual sleep
      times and this was reflected on the MEQ. There was, however, significant
      variability in the TBI group's change from the pre-injury to the current MEQ
      score. The timing of melatonin onset was not different between the groups. While
      subtle changes (advances or delays) in this small sample may have cancelled each
      other out,. the present study does not provide conclusive objective evidence of
      shift in circadian timing of sleep following TBI. Furthermore, although
      participants did report sleep timing changes, it is concluded that the MEQ may
      not be suitable for use with this cognitively impaired clinical group.

PMID- 15865325
TI  - Increased occurrence of out-of-hospital cardiac arrest on Mondays in a community
      based study.
AB  - Acute myocardial infarction and sudden cardiac death are more common on Mondays
      than other days of the week. The stress of returning to work at the beginning of
      the week has been postulated as a possible trigger factor. This project examined
      the weekly variation of out-of-hospital cardiac arrests of nontraumatic origin
      for the entire case series as well as for selected subgroups. A retrospective
      analysis of 1,498 incidences between January 1, 1995 and December 31, 1996
      revealed a distinct Monday peak in occurrence irrespective of age, gender,
      presence of witnesses, primary survival, or primary ECG. This finding, however,
      was most pronounced in retired patients, subjects living alone, and persons found
      unconscious outside buildings or in public places. One important trigger of
      cardiac arrest is going to work after weekends; however, resumption of social and
      other activities on Mondays is another possible trigger. Other factors, such as
      endogenous biological rhythms, may contribute to an increased risk at this
      particular time even in elderly.

PMID- 15865326
TI  - Further assessments of the relationship between jet lag and some of its symptoms.
AB  - The disruption of circadian rhythms following time-zone transitions gives rise to
      the syndrome of jet lag. The power of some of the symptoms of jet lag to predict
      the amount of jet lag measured at the same and at different times of the day has
      been investigated. Eleven healthy subjects were studied in an Isolation Unit for
      two days after a simulated flight from the UK to Beijing (8 time zones to the
      east). At six time-points (08:30, 11:00, 14:00, 17:00, 20:00, and 23:00 h), the
      subjects recorded their jet lag, and the differences from "normal" (that is, from
      days in which there is no jet lag) of alertness, hunger, indigestion,
      concentration, motivation, and irritability. They recorded at 08:30 h the type of
      food they had eaten since rising at 08:00h and, at the other times, the type of
      food eaten in the last three hours. Assessments were made by visual analogue
      scales or, in the case of type of food, by a nominal scale. Following the time
      zone transition, the adjustment of meals appeared to be complete almost
      immediately. Jet lag and its symptoms were present during both experimental days.
      Jet lag tended to rise during the course of the daytime, accompanied by falls in
      alertness, motivation, and concentration. Correlation matrices between jet lag
      and each of the other variables were produced, using lags between the variable
      (from up to 5 time-points before the assessment of jet lag to 5 time-points
      afterwards) and pooling the results from both days. These matrices indicated that
      significant correlations existed only between jet lag and alertness,
      concentration, and motivation, and then only when these other variables were
      assessed at the same time as jet lag or 1 or 2 time-points earlier. Jet lag was
      then treated as the dependent variable and the symptoms as covariates in analysis
      of covariances (ANCOVAs), with the days treated as a random effect. This analysis
      enabled the significance of potential predictors of jet lag, together with their
      beta-coefficients (the relationship between a unit change of each significant
      predictor and the change in jet lag), to be calculated. Falls in alertness and
      motivation were significant predictors of increased jet lag, provided that they
      were measured at the same time, when they accounted for about 50% of the jet lag;
      when measured at other time-points, they did not act as significant predictors.
      It is concluded that the amount of jet lag varies during the course of the day
      and that it can be predicted from contemporaneous assessments of alertness and
      motivation-but not from assessments made at other times of the day, nor from
      other variables that are symptoms of jet lag, even though these other variables
      are significantly increased. In considering the results of this and our previous
      study, we reiterate the view that the exact meaning of "jet lag" is complex and
      that the particular combination of factors that contribute to it might vary with
      the time of day that the assessment is made. Inferences about any decrements due
      to time-zone transitions cannot be made reliably at times of the day that differ
      from the time when jet lag is assessed.

PMID- 15865327
TI  - Circadian rhythm of acute phase proteins under the influence of bright/dim light
      during the daytime.
AB  - We investigated the influence of two different light intensities, dim (100 lx)
      and bright (5000 lx), during the daytime on the circadian rhythms of selected
      acute phase proteins of C-reactive protein (CRP), alpha1-acid glycoprotein (AGP),
      alpha1-antichymotrypsin (ACT), transfferin (TF), alpha2-macroglobulin (alpha2-m),
      haptoglobin (HP), and ceruloplasmin (CP). Serum samples were collected from 7
      healthy volunteers at 4 h intervals during two separate single 24 h spans during
      which they were exposed to the respective light intensity conditions. A circadian
      rhythm was detected only in ACT concentration in the bright light condition. The
      concentration of ACT, a positive acute phase protein (APP), increased
      (significantly significant differences in the ACT concentration were detected at
      14:00 and 22:00 h) and AGP showed a tendency to be higher under the daytime
      bright compared to dim light conditions. There were no significant differences
      between the time point means under daytime dim and bright light conditions for
      alpha2-M, AGP, Tf, Cp, or Hp. The findings suggest that some, but not all, APP
      may be influenced by the environmental light intensity.

PMID- 15865328
TI  - Dysregulation of circadian rhythms following prolactin-secreting pituitary
      microadenoma.
AB  - A patient who developed an irregular sleep-wake pattern following prolactin
      secreting pituitary microadenoma is described. The patient reported difficulties
      in sleep onset and awakening at the desired time, which caused major dysfunction
      in his daily life activities. Despite these difficulties, the sleep-related
      complaints of the patient remained unrecognized for as long as three yrs.
      Statistical analyses of the patient's rest-activity patterns revealed that the
      disruption of the sleep-wake circadian rhythm originated from a disharmony
      between ultradian (semicircadian) and circadian components. The circadian
      component displayed shorter than 24 h periodicity most of the time, but the
      semicircadian component fluctuated between longer and shorter than 12 h periods.
      Additionally, desynchrony in terms of period length was found in the tentative
      analyses of the rest-activity pattern, salivary melatonin, and oral temperature.
      While the salivary melatonin time series data could be characterized by a best
      fit cosine curve of 24 h, the time series data of oral temperature was more
      compatible with 28 h best-fit curve. The rest-activity cycle during the
      simultaneous measurements, however, was best approximated by a best-fit curve of
      21 h. The dysregulation of circadian rhythms occurred concomitantly, but not
      beforehand, with the onset of pituitary disease, thus suggesting an association
      between the two phenomena. This association may have interesting implications to
      the modeling of the circadian time-keeping system. This case also highlights the
      need to raise the awareness to circadian rhythm sleep disorders and to consider
      disruptions of sleep-wake cycle in patients with pituitary adenoma.

PMID- 15865329
TI  - The empirical limits of forensic mental health assessment.
AB  - This article introduces a special issue of Law and Human Behavior, including five
      articles describing the limits of forensic mental health assessments of (a) risk
      of violence in female adolescents, (b) sexually violent predators, (c)
      dangerousness in capital murder cases, (d) child sexual abuse, and (e) PTSD
      litigants. Knowing the limits of forensic mental health assessment methods is
      essential in order to recognize their strengths, increase the credibility of
      forensic mental health assessment, and drive research that will enhance the value
      of assessments for the courts.

PMID- 15865330
TI  - Examining the science and practice of violence risk assessment with female
      adolescents.
AB  - While the field of violence risk assessment among adult males has progressed
      rapidly, several questions remain with respect to the application of forensic
      risk assessment tools within other populations. In this article, we consider the
      empirical evidence for the assessment, prediction, and management of violence in
      adolescent girls. We discuss limitations of generalizing violence risk assessment
      findings from other populations to adolescent girls and point out areas where
      there is little or no empirical foundation. Critical issues that must be
      addressed in research prior to the adoption or rejection of such instruments are
      delineated. Finally, we provide practice guidelines for clinicians currently
      involved with adolescent females within risk assessment contexts.

PMID- 15865331
TI  - Sexually violent predator evaluations: empirical evidence, strategies for
      professionals, and research directions.
AB  - Several states have passed civil commitment laws that allow the precautionary
      detention of sex offenders who have completed their criminal sentences. Over
      2,500 sex offenders have been committed across states with such statutes and
      several thousand more sex offenders have been evaluated. Most statutes call for
      an evaluation of risk by a mental health professional and, although each state
      statute is worded differently, three main elements common to sexually violent
      predator evaluations are used to guide evaluators: mental abnormality, volitional
      capacity, and likelihood of future sexual violence. The current article presents
      empirical evidence for the main tenants of these forensic evaluations, provides
      recommendations for evaluators in light of current limitations of evidence, and
      offers suggestions for future research in this area of forensic assessment.

PMID- 15865332
TI  - Predictions of future dangerousness in capital murder trials: is it time to
      "disinvent the wheel"?
AB  - Although recent U.S. Supreme Court decisions regarding the death penalty (e.g.,
      Atkins v. Virginia, 2002) have renewed interest in mental health issues, one
      topic that has not received much attention recently is the ongoing use of expert
      testimony to support claims that defendants represent a "continuing threat to
      society." In this article, we (a) review prior research relevant to determining
      the accuracy of clinical predictions that capital defendants will commit future
      acts of criminal violence; (b) summarize new data from current and former death
      row inmates in Texas that bolster the claim that such predictions are gross
      overestimates of risk; and (c) review extant research addressing the potential
      utility of various risk assessment instruments that increasingly are being used
      to reinforce clinical predictions in capital trials. Despite significant recent
      advances in the field of risk assessment, clinical assertions that a defendant is
      likely to commit future violent acts appear to be highly inaccurate and ethically
      questionable at best. Moreover, available research offers little support for the
      claim that the accuracy of these predictions will be appreciably improved by
      relying on more structured risk assessment measures that have some demonstrated
      predictive validity in other contexts.

PMID- 15865333
TI  - Improving decision making in forensic child sexual abuse evaluations.
AB  - Mental health professionals can assist legal decision makers in cases of
      allegations of child sexual abuse by collecting data using forensic interviews,
      psychological testing, and record reviews, and by summarizing relevant findings
      from social science research. Significant controversy surrounds another key task
      performed by mental health professionals in most child sexual abuse evaluations,
      i.e., deciding whether or not to substantiate unconfirmed abuse allegations. The
      available evidence indicates that, on the whole, these substantiation decisions
      currently lack adequate psychometric reliability and validity: an analysis of
      empirical research findings leads to the conclusion that at least 24% of all of
      these decisions are either false positive or false negative errors. Surprisingly,
      a reanalysis of existing research also indicates that it may be possible to
      develop reliable, objective procedures to improve the consistency and quality of
      decision making in this domain. A preliminary, empirically-grounded procedure for
      making substantiation decisions is proposed.

PMID- 15865334
TI  - Empirical limits for the forensic assessment of PTSD litigants.
AB  - This paper discusses the limits of expert opinion on posttraumatic stress
      disorder (PTSD) in personal injury claims. The construct of PTSD is hampered by
      several empirical limitations. Multiple reliable measures of PTSD exist, but have
      not been evaluated sufficiently within litigating samples and are infrequently
      used by forensic assessors. Common methods for trauma screening appear
      insensitive. Opinions about causation of PTSD and disability are complicated by
      retrospective memory biases, as well as the failure of most anxiety disorders to
      be detected within primary medical care. PTSD appears to have a steep spontaneous
      remission curve during the first year, but at least 10% of trauma-exposed people
      suffer chronic distress. Little is known about the course beyond 1 year.
      Efficacious psychological treatments have been developed for PTSD, but are not in
      common use limiting claimants' access to rehabilitative treatments. Research on
      functional disability associated with PTSD is in its infancy, but it seems likely
      that PTSD will account for only a part of the variance in work disability. We
      provide suggestions for improving forensic practice, advising the courts about
      the limitations of forensic opinions, and necessary research.

PMID- 15865335
TI  - Modeling natural attenuation of benzene with analytical and numerical models.
AB  - Natural attenuation of benzene is a much-accepted technology for remediating low
      risk sites. To date, numerous protocols have been developed for assessing natural
      attenuation and measuring indicator parameters. Many models have additionally
      been developed to describe the advection, dispersion, sorption and biodegradation
      processes involved. It is evident that while there is extensive guidance in
      natural attenuation protocols for field sampling methodologies, less emphasis is
      placed on analyzing natural attenuation data for supporting appropriate model
      development. This paper presents methodologies for data analysis and
      interpretation that may be undertaken to achieve data reduction for modeling
      purposes. A case study is presented to illustrate the use of an analytical and a
      numerical natural attenuation model at the same site for predicting the time
      required to achieve the remedial goal at the site.

PMID- 15865336
TI  - Depolymerisation and biodegradation of a synthetic tanning agent by activated
      sludges, the bacteria Arthrobacter globiformis and Comamonas testosteroni, and
      the fungus Cunninghamella polymorpha.
AB  - Degradation of a synthetic tanning agent CNSF (a condensation product of 2
      naphthalenesulfonic acid (2-NSA) and formaldehyde) by four activated sludges, two
      previously characterised bacterial strains, Arthrobacter sp. 2AC and Comamonas
      sp. 4BC, and the fungus Cunninghamella polymorpha, was studied in batch culture
      at 25 degrees C by determining the changes in the concentrations of CNSF and its
      component monomers and oligomers (n2-n11). The loss of individual oligomers was
      correlated with the length of the NSA-CH2 chain. Approximately 25% of the total
      CNSF was degraded (i.e. mineralised) by the microbes contained in the four
      activated sludges and by the two bacterial isolates but with different lag phases
      and at different overall rates. The decline in CNSF concentration was due almost
      entirely to the biodegradation of the monomers (34.3% of CNSF) and, in
      particular, 2-NSA (27% of CNSF). There was no change in the n2-n11 components.
      The growth of C. polymorpha, on the other hand, arose from extracellular
      depolymerisation of CNSF oligomers and the biodegradation of the lower molecular
      mass products. Between 38% and 42% of total CNSF was degraded by C. polymorpha at
      25 degrees C. The order of oligomer degradation was inversely related to degree
      of polymerisation. Eighty percent and 90% of the n4 and n5 and 100% oligomers n6
      n11 were degraded after 120 h. At a higher temperature (37 degrees C) oligomers
      n4-n11 were degraded completely after 120 h. A combination of biodegradation
      (75%) and sorption to fungal biomass (25%) accounted for the measured loss of all
      oligomers from the solution phase. The CNSF degradation rates and the volume of
      fungal biomass produced (and therefore the extent of biosorption) were dependent
      on the presence of a second carbon source (both optimum at glucose 5 g/l). This
      is the first report that identifies and distinguishes between depolymerisation,
      sorption and biodegradation processes in the removal of CNSF and its component
      oligomers. The use of combinations of the depolymerising fungus C. polymorpha,
      and the monomer-degrading bacteria, Arthrobacter sp. 2AC and Comamonas sp. 4BC,
      have potential for wastewater treatment.

PMID- 15865337
TI  - Kinetics of BTEX biodegradation by a coculture of Pseudomonas putida and
      Pseudomonas fluorescens under hypoxic conditions.
AB  - Pseudomonas putida and Pseudomonas fluorescens present as a coculture were
      studied for their abilities to degrade benzene, toluene, ethylbenzene, and
      xylenes (collectively known as BTEX) under various growth conditions. The
      coculture effectively degraded various concentrations of BTEX as sole carbon
      sources. However, all BTEX compounds showed substrate inhibition to the bacteria,
      in terms of specific growth, degradation rate, and cell net yield. Cell growth
      was completely inhibited at 500 mg l(-1) of benzene, 600 mg l(-1) of o-xylene,
      and 1000 mg l(-1) of toluene. Without aeration, aerobic biodegradation of BTEX
      required additional oxygen provided as hydrogen peroxide in the medium. Under
      hypoxic conditions, however, nitrate could be used as an alternative electron
      acceptor for BTEX biodegradation when oxygen was limited and denitrification took
      place in the culture. The carbon mass balance study confirmed that benzene and
      toluene were completely mineralized to CO2 and H2O without producing any
      identifiable intermediate metabolites.

PMID- 15865338
TI  - Enhanced biodegradation of phenol by a microbial consortium in a solid-liquid two
      phase partitioning bioreactor.
AB  - Two phase partitioning bioreactors (TPPBs) operate by partitioning toxic
      substrates to or from an aqueous, cell-containing phase by means of second
      immiscible phase. Uptake of toxic substrates by the second phase effectively
      reduces their concentration within the aqueous phase to sub-inhibitory levels,
      and transfer of molecules between the phases to maintain equilibrium results in
      the continual feeding of substrate based on the metabolic demand of the
      microorganisms. Conventionally, a single pure species of microorganism, and a
      pure organic solvent, have been used in TPPBs. The present work has demonstrated
      the benefits of using a mixed microbial population for the degradation of phenol
      in a TPPB that uses solid polymer beads (comprised of ethylene vinyl acetate, or
      EVA) as the second phase. Polymer modification via an increase in vinyl acetate
      concentration was also shown to increase phenol uptake. Microbial consortia were
      isolated from three biological sources and, based on an evaluation of their
      kinetic performance, a superior consortium was chosen that offered improved
      degradation when compared to a pure strain of Pseudomonas putida ATCC 11172. The
      new microbial consortium used within a TPPB was capable of degrading high
      concentrations of phenol (approximately 2000 mg l(-1)), with decreased lag time
      (10 h) and increased specific rate of phenol degradation (0.71 g phenol g(1) cell
      h). Investigation of the four-member consortium showed that it consisted of two
      Pseudomonas sp., and two Acinetobacter sp., and tests conducted upon the
      individual isolates, as well as paired organisms, confirmed the synergistic
      benefit of their existence within the consortium. The enhanced effects of the use
      of a microbial consortium now offer improved degradation of phenol, and open the
      possibility of the degradation of multiple toxic substrates via a polymer
      mediated TPPB system.

PMID- 15865339
TI  - Anaerobic biodegradation of vegetable oil and its metabolic intermediates in oil
      enriched freshwater sediments.
AB  - Anaerobic biodegradation of vegetable oil in freshwater sediments is strongly
      inhibited by high concentrations of oil, but the presence of ferric hydroxide
      relieves the inhibition. The effect of ferric hydroxide is not due to physical or
      chemical interactions with long-chain fatty acids (LCFAs) that are produced as
      intermediates during metabolism of vegetable-oil triglycerides. The anaerobic
      biodegradation of canola oil and mixtures of acetic and oleic acids, two
      important intermediates of vegetable-oil metabolism, were investigated using
      sediments enriched on canola oil under methanogenic and iron-reducing conditions
      to determine whether the effect of ferric hydroxide has a biological basis.
      Sediments enriched under both conditions rapidly and completely converted canola
      oil to methane when the initial oil concentration was relatively low (1.9 g
      oil/kg sediments), but the biotransformation was strongly inhibited in sediments
      enriched under methanogenic conditions when the initial concentration was 19 g/kg
      (< 30% of the oil-derived electron equivalents were transferred to methane in a
      420-day incubation period). Sediments enriched under iron-reducing conditions,
      however, completely transformed canola oil to methane in about 250 days at this
      initial oil concentration. The anaerobic biotransformation of mixtures of acetate
      and oleic acid followed a similar pattern: the rate and extent of conversion of
      these electron-donor substrates to methane was always higher in sediments
      enriched under iron-reducing than under methanogenic conditions. These results
      suggest that enrichment on canola oil in the presence of ferric hydroxide selects
      a microbial community that is less sensitive to inhibition by LCFAs than the
      community that develops during enrichment under methanogenic conditions.

PMID- 15865340
TI  - Identification and characterization of hydroxyquinone hydratase activities from
      Sphingobium chlorophenolicum ATCC 39723.
AB  - Hydroxyquinol, a common metabolite of aromatic compounds, is readily auto
      oxidized to hydroxyquinone. Enzymatic activities that metabolized hydroxyquinone
      were observed from the cell extracts of Sphingobium chlorophenolicum ATCC 39723.
      An enzyme capable of transforming hydroxyquinone was partially purified, and its
      activities were characterized. The end product was confirmed to be 2,5
      dihydroxyquinone by comparing UV/Vis absorption spectra, electrospray mass
      spectra, and gas chromatography-mass spectra of the end product and the authentic
      compound. We have proposed that the enzyme adds a H2O molecule to hydroxyquinone
      to produce 2,5-dihydroxycyclohex-2-ene-1, 4-dione, which spontaneously rearranges
      to 1, 2,4,5-tetrahydroxybenzene. The latter is auto-oxidized by O2 to 2,5
      dihydroxyquinone. The proposed pathway was supported by the overall reaction
      stoichiometry. Thus, the transformation of hydroxyquinol to 2,5-dihydroxyquinone
      involves two auto-oxidation of quinols and one enzymatic reaction catalyzed by a
      hydratase. The specific enzymatic step did not require O2, further supporting the
      assignment as a hydratase. To our knowledge, this is the first identification of
      a quinone hydratase, enhancing the knowledge on microbial metabolism of
      hydroxyquinone and possibly leading to the development of enzymatic method for
      the production of 2,5-dihydroxyquinone, a widely used chemical in various
      industrial applications.

PMID- 15865341
TI  - Biodegradation of hexachlorocyclohexane (HCH) by microorganisms.
AB  - The organochlorine pesticide Lindane is the gamma-isomer of hexachlorocyclohexane
      (HCH). Technical grade Lindane contains a mixture of HCH isomers which include
      not only gamma-HCH, but also large amounts of predominantly alpha-, beta- and
      delta-HCH. The physical properties and persistence of each isomer differ because
      of the different chlorine atom orientations on each molecule (axial or
      equatorial). However, all four isomers are considered toxic and recalcitrant
      worldwide pollutants. Biodegradation of HCH has been studied in soil, slurry and
      culture media but very little information exists on in situ bioremediation of the
      different isomers including Lindane itself, at full scale. Several soil
      microorganisms capable of degrading, and utilizing HCH as a carbon source, have
      been reported. In selected bacterial strains, the genes encoding the enzymes
      involved in the initial degradation of Lindane have been cloned, sequenced,
      expressed and the gene products characterized. HCH is biodegradable under both
      oxic and anoxic conditions, although mineralization is generally observed only in
      oxic systems. As is found for most organic compounds, HCH degradation in soil
      occurs at moderate temperatures and at near neutral pH. HCH biodegradation in
      soil has been reported at both low and high (saturated) moisture contents. Soil
      texture and organic matter appear to influence degradation presumably by sorption
      mechanisms and impact on moisture retention, bacterial growth and pH. Most
      studies report on the biodegradation of relatively low (< 500 mg/kg)
      concentrations of HCH in soil. Information on the effects of inorganic nutrients,
      organic carbon sources or other soil amendments is scattered and inconclusive.
      More in-depth assessments of amendment effects and evaluation of bioremediation
      protocols, on a large scale, using soil with high HCH concentrations, are needed.

PMID- 15865342
TI  - Bioconversion of lignocellulosic waste from selected dumping sites in Dar es
      Salaam, Tanzania.
AB  - The poor management of solid wastes in Tanzania urban centers is a chronic
      problem that has increasingly become a source of environmental pollution.
      Bioconversion offers a cheap and safe method of not only disposing these wastes,
      but also it has the potential to convert lignocellulosic wastes into usable forms
      such as reducing sugars that could be used as food. This paper reports a
      preliminary study on the physical characteristics, acid pretreatment,
      saccharification by cellulase from Trichoderma reesei and fermentation by
      Saccharomyces cerevisiae of the lignocellulosic component of the solid wastes
      collected from various dumping sites located in Kinondoni Municipality, Dar es
      Salaam city. The results showed that overall, the lignocellulosic component
      constitute about 50% of solid wastes dumped in the study areas. Maximum
      production of reducing sugars was obtained after 6h of saccharification while
      highest concentrations of bioethanol were achieved after 48 h of fermentation.
      Microbial bioconversion of lignocellulose component yielded up to 21% bioethanol.

PMID- 15865343
TI  - Natural selection for 2,4,5-trichlorophenoxyacetic acid mineralizing bacteria in
      agent orange contaminated soil.
AB  - Agent Orange contaminated soils were utilized in direct enrichment culture
      studies to isolate 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4
      dichlorophenoxyacetic acid (2,4-D) mineralizing bacteria. Two bacterial cultures
      able to grow at the expense of 2,4,5-T and/or 2,4-D were isolated. The 2,4,5-T
      degrading culture was a mixed culture containing two bacteria, Burkholderia
      species strain JR7B2 and Burkholderia species strain JR7B3. JR7B3 was able to
      metabolize 2,4,5-T as the sole source of carbon and energy, and demonstrated the
      ability to affect metabolism of 2,4-D to a lesser degree. Strain JR7B3 was able
      to mineralize 2,4,5-T in pure culture and utilized 2,4,5-T in the presence of
      0.01% yeast extract. Subsequent characterization of the 2,4-D degrading culture
      showed that one bacterium, Burkholderia species strain JRB1, was able to utilize
      2,4-D as a sole carbon and energy source in pure culture. Polymerase chain
      reaction (PCR) experiments utilizing known genetic sequences from other 2,4-D and
      2,4,5-T degrading bacteria demonstrated that these organisms contain gene
      sequences similar to tfdA, B, C, E, and R (Strain JRB1) and the tftA, C, and E
      genes (Strain JR7B3). Expression analysis confirmed that tftA, C, and E and tfdA,
      B, and C were transcribed during 2,4,5-T and 2,4-D dependent growth,
      respectively. The results indicate a strong selective pressure for 2,4,5-T
      utilizing strains under field condition.

PMID- 15865344
TI  - Degradation of benz[a]anthracene by Mycobacterium vanbaalenii strain PYR-1.
AB  - Cultures of Mycobacterium vanbaalenii strain PYR-1 grown in mineral salts medium
      and nutrients in the presence of benz[a]anthracene metabolized 15% of the added
      benz[a]anthracene after 12 days of incubation. Neutral and acidic ethyl acetate
      extractable metabolites were isolated and characterized by high performance
      liquid chromatography (HPLC) and uv-visible absorption, gas chromatography/mass
      (GC/MS) and nuclear magnetic resonance (NMR) spectral analysis.
      Trimethylsilylation of the metabolites followed by GC/MS analysis facilitated
      identification of metabolites. The characterization of metabolites indicated that
      M. vanbaalenii initiated attack of benz[a]anthracene at the C-1,2-, C-5,6-, C
      7,12- and C-10,11-positions to form dihydroxylated and methoxylated
      intermediates. The major site of enzymatic attack was in the C-10, C-11
      positions. Subsequent ortho- and meta-cleavage of each of the aromatic rings led
      to the accumulation of novel ring-fission metabolites in the medium. The major
      metabolites identified were 3-hydrobenzo[f]isobenzofuran-1-one (3.2%), 6
      hydrofuran[3,4-g]chromene-2,8-dione (1.3%), benzo[g]chromene-2-one (1.7%),
      naphtho[2,1-g]chromen-10-one (48.1%), 10-hydroxy-11-methoxybenz[a]anthracene
      (9.3%), and 10,11-dimethoxybenz[a]anthracene (36.4%). Enzymatic attack at the C-7
      and C-12 positions resulted in the formation of benz[a]anthracene-7,12-dione, 1
      (2-hydroxybenzoyl)-2-naphthoic acid, and 1-benzoyl-2-naphthoic acid. A phenyl
      naphthyl metabolite, 3-(2-carboxylphenyl)-2-naphthoic acid, was formed when M.
      vanbaalenii was incubated with benz[a]anthracene cis-5,6-dihydrodiol, indicating
      ortho-cleavage of 5,6-dihydroxybenz[a]anthracene. A minor amount of 5,6
      dimethoxybenz[a]anthracene was also formed. The data extend and propose novel
      pathways for the bacterial metabolism of benz[a]anthracene.

PMID- 15865345
TI  - Fate and biodegradability of sulfonated aromatic amines.
AB  - Ten sulfonated aromatic amines were tested for their aerobic and anaerobic
      biodegradability and toxicity potential in a variety of environmental inocula. Of
      all the compounds tested, only two aminobenzenesulfonic acid (ABS) isomers, 2-
      and 4-ABS, were degraded. The observed degradation occurred only under aerobic
      conditions with inocula sources that were historically polluted with sulfonated
      aromatic amines. Bioreactor experiments, with non-sterile synthetic wastewater,
      confirmed the results from the aerobic batch degradation experiments. Both ABS
      isomers were degraded in long-term continuous experiment by a bioaugmented
      enrichment culture. The maximum degradation rate in the aerobic bioreactor was
      1.6-1.8 g 1(-1) d(-1) for 2-ABS and a somewhat lower value for 4-ABS at hydraulic
      retention times (HRT) of 2.8-3.3 h. Evidence for extensive mineralization of 2-
      and 4-ABS was based on oxygen uptake and carbon dioxide production during the
      batch experiments and the high levels of chemical oxygen demand (COD) removal in
      the bioreactor. Furthermore, mineralization of the sulfonate group was
      demonstrated by high recovery of sulfate. The sulfonated aromatic amines did not
      show any toxic effects on the aerobic and anaerobic bacterial populations tested.
      The poor biodegradability of sulfonated aromatic amines indicated under the
      laboratory conditions of this study suggests that these compounds may not be
      adequately removed during biological wastewater treatment.

PMID- 15865346
TI  - Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) degradation by Acetobacterium
      paludosum.
AB  - Substrates and nutrients are often added to contaminated soil or groundwater to
      enhance bioremediation. Nevertheless, this practice may be counterproductive in
      some cases where nutrient addition might relieve selective pressure for pollutant
      biodegradation. Batch experiments with a homoacetogenic pure culture of
      Acetobacterium paludosum showed that anaerobic RDX degradation is the fastest
      when auxiliary growth substrates (yeast extract plus fructose) and nitrogen
      sources (ammonium) are not added. This bacterium degraded RDX faster under
      autotrophic (H2-fed) than under heterotrophic conditions, even though
      heterotrophic growth was faster. The inhibitory effect of ammonium is postulated
      to be due to the repression of enzymes that initiate RDX degradation by reducing
      its nitro groups, based on the known fact that ammonia represses nitrate and
      nitrite reductases. This observation suggests that the absence of easily
      assimilated nitrogen sources, such as ammonium, enhances RDX degradation.
      Although specific end products of RDX degradation were not determined, the
      production of nitrous oxide (N2O) suggests that A. paludosum cleaved the triazine
      ring.

PMID- 15865347
TI  - Influence of pH shocks on trace metal dynamics and performance of methanol fed
      granular sludge bioreactors.
AB  - The influence of pH shocks on the trace metal dynamics and performance of
      methanol fed upflow anaerobic granular sludge bed (UASB) reactors was
      investigated. For this purpose, two UASB reactors were operated with metal pre
      loaded granular sludge (1 mM Co, Ni and Fe; 30 degrees C; 96 h) at an organic
      loading rate (OLR) of 5 g COD 1 reactor(-1) d(-1). One UASB reactor (R1) was
      inoculated with sludge that originated from a full scale reactor treating alcohol
      distillery wastewater, while the other reactor (R2) was inoculated with sludge
      from a full scale reactor treating paper mill wastewater. A 30 h pH shock (pH 5)
      strongly affected the metal retention dynamics within the granular sludge bed in
      both reactors. Iron losses in soluble form with the effluent were considerable:
      2.3 and 2.9% for R1 and R2, respectively, based on initial iron content in the
      reactors, while losses of cobalt and nickel in soluble form were limited.
      Sequential extraction of the metals from the sludge showed that cobalt, nickel,
      iron and sulfur were translocated from the residual to the organic/sulfide
      fraction during the pH shock in R2, increasing 34, 47, 109 and 41% in the
      organic/sulfide fraction, respectively. This is likely due to the modification of
      the iron sulfide precipitate stability, which influences the extractability of
      iron and trace metals. Such a translocation was not observed for the R1 sludge
      during the first 30 h pH shock, but a second 4 day pH shock induced significant
      losses of cobalt (18%), iron (29%) and sulfur (29%) from the organic/sulfide
      fraction, likely due to iron sulfide dissolution and concomitant release of
      cobalt. After the 30 h pH shock, VFA accumulated in the R2 effluent, whereas both
      VFA and methanol accumulated in R1 after the 4 day pH shock. The formed VFA,
      mainly acetate, were not converted to methane due to the loss of methanogenic
      activity of the sludge on acetate. The VFA accumulation gradually disappeared,
      which is likely to be related to out-competition of acetogens by methanogens.
      Zinc, copper and manganese supply did not have a clear effect on the acetate
      removal and methanol conversion, but zinc may have induced the onset of methanol
      degradation after day 152 in R1.

PMID- 15865348
TI  - Evaluation of different bioremediation protocols to enhance decomposition of
      organic polymers in harbour sediments.
AB  - The response of the microbial community (in term of abundance and enzymatic
      activity) was investigated to test the effect of different bioremediation
      protocols to naturally enhance decomposition of organic polymers in harbour
      sediments (Genoa Harbour, Italy, N-W Mediterranean). Bioremediation techniques
      tested were bioaugmentation (5 different microorganisms' inocula), biostimulation
      (air supply), and natural attenuation. The coupling
      bioaugmentation/biostimulation was also tested. After 60 days, following the
      bioaugmentation protocol, bacterial densities correlated to the quantities of
      inocula amended to the boxes, suggesting that allochthonous community was able to
      survive and multiply. However, while bioaugmentation alone seems not to be able
      to carry out significative degradation, its coupling with air insufflations
      produced the best response: here bacterial densities increased, especially in the
      water (from 2.3 x 10(7) to 3.50 x 10(8) cells ml(-1)), average cell size and
      enzymatic activities increased, and sedimentary organic matter was significantly
      depleted (PRT 5-folds reduction, CHO 1.5-folds reduction). The strong coupling
      observed between the sediment and water compartments together with the greatest
      microbial response observed in this latter suggest that the sediment-water
      interface may constitute a key compartment for the occurring of biodegradation
      processes in organic-rich sediments.

PMID- 15865349
TI  - Biodegradation of beta-cyfluthrin by Pseudomonas stutzeri strain S1.
AB  - beta-Cyfluthrin [alpha-cyano-4-fluoro-3-phenoxybenzyl-3(2,2-dichlorovinyl)-2,2
      dimethylcyclopropane carboxylate] pesticide has been in agricultural use in the
      recent years for controlling Lepidopteran pests affecting solanaceous crops. The
      extensive use of synthetic pyrethroids like beta-cyfluthrin has resulted in wide
      spread environmental contamination. The purpose of this study was to isolate
      bacteria from soil and to determine their ability to degrade beta-cyfluthrin and
      identify the intermediates in culture broth using spectroscopy. An aerobic
      bacterium capable of degrading beta-cyfluthrin was isolated by enrichment
      culture. The 16S ribosomal DNA sequence of the isolate (strain S1) had 100%
      identity to the sequence from Pseudomonas stutzeri. Finally products formed
      during degradation of beta-cyfluthrin have been identified as alpha-cyano-4
      fluoro-3-phenoxybenzyl-3(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate
      (M.W. 341); 4-fluoro-3-phenoxy-alpha-cyanobenzyl alcohol (M.W. 243) and 3(2,2
      dichlorovinyl)-2,2-dimethyl cyclopropanecarboxylic acid (M.W. 208).

PMID- 15865350
TI  - Development of a PCR method for the detection and quantification of benzoyl-CoA
      reductase genes and its application to monitored natural attenuation.
AB  - Benzoyl coenzyme A reductase (BCR) catalyzes dearomatization of benzoyl coenzyme
      A (benzoyl-CoA), which is the central step in the anaerobic degradative pathways
      for a variety of aromatic compounds. This study developed a PCR method for the
      detection and quantification of BCR genes in bacterial strains and environmental
      samples. PCR primers were designed by aligning known BCR genes in Thauera,
      Azoarcus and Rhodopseudomonas species, and their utility was assessed by
      amplifying BCR fragments from aromatic-hydrocarbon degrading anaerobes and other
      bacteria. BCR fragments with the expected sizes were obtained from denitrifying
      and phototrophic aromatics degraders. The positive signals were also obtained
      from Geobacter metallireducens and xylene-degrading sulfate-reducing bacterium
      (strain mXyS1) but not from other aromatics-degrading sulfate-reducing bacteria
      and aerobic bacteria. When the PCR was used for analyzing a natural attenuation
      (NA) site, the positive signal was obtained only from gasoline-contaminated
      groundwater; sequence analysis of these amplicons revealed that most of them
      exhibited substantial similarities to the known BCRs. Quantitative competitive
      PCR analysis estimated BCR-gene copies to account for 10-40% of bacterial 16S
      rRNA gene copies in the contaminated groundwater, indicating that bacteria
      possessing BCR genes were highly enriched in the contaminated groundwater. In
      microcosm bioremediation tests using the contaminated groundwater, the copy
      number of BCR gene was approximately 10-fold increased in the course of aromatics
      degradation under denitrifying conditions but not under sulfidogenic conditions.
      These results suggest the utility of the PCR method for assessing the potential
      of denitrifying bacteria for aromatic-compound degradation in groundwater.

PMID- 15865351
TI  - [Obesity is a chronic disease].

PMID- 15865352
TI  - [Burden of obesity: from epidemic to costs].
AB  - Nowadays, we count over 300 million obese in the world and this figure could
      double in twenty years. In industrialised countries, the prevalence of obesity is
      between 15 and 30%. In 2002, one third of the Swiss population suffers from
      excess body weight and obesity represents 7.7%. An increase of daily energy
      intake and a reduction of physical activity are the main causes. In 2001, the
      global costs induced by obesity and excess body weight in Switzerland reached CHF
      2,690 billion. 98.4% of costs are due to obesity complications and only 1.6% are
      linked to the treatment of obesity without complication. Further prevention could
      be done with children and within a poor socio-economic population.

PMID- 15865354
TI  - [Hypocaloric diets: which ones to advise/avoid?].
AB  - A hypocaloric diet, whatever the proposed type, is an inadapted treatment to
      chronic disease, like obesity. All diets are inefficient on the long term. The
      weight loss is generally small, about 1-2 kg a year. The results are the same,
      independently of the type of diet, and the patient's compliance is clearly the
      main key to succeed. About 80% of patients regain weight the first month
      following the diet, and only 1% can keep the obtained weight a year later. Nearly
      half of the patients involved in a diet program give up before the end. Finally,
      because of risks of macro and micro nutriments deficiency, certain diets are to
      be avoided and hypocaloric diet shouldn't be proposed.

PMID- 15865353
TI  - [Dieting or non-dieting?].
AB  - Dieting is a widespread behaviour responding to the public health
      recommendations. In the setting of weight cycling, this positive health behaviour
      can have physical and psychological negative consequences. This review of
      interventions is focused on the psychological consequences of dieting among the
      obese population. Based on the randomised controlled trials published in the last
      ten years, it seems that our biggest challenge should be the modification of our
      programs and the whole mind set regarding the treatment of obesity.

PMID- 15865355
TI  - [Managing obesity and binge eating disorders].
AB  - Binge eating disorder is frequent in patients suffering from obesity. Such
      disorders must be detected through the DSM-IV criteria. Binge eating disorder
      must be taken into account during the treatment in order to diminish the relapse
      and the "yoyo" phenomenon. The treatment consists in a cognitive-behavioural
      therapy associated with nutritional approach and favouring physical activity.
      Even if eating disorders are treated as a priority in psychotherapy, the GP's
      caring can be done at different levels: examine patients' expectations, weight
      loss objectives 1-3 kg/month), their motivation to change, encourage them to
      structure their meals, or help them find binge eating stimuli and their own
      strategies.

PMID- 15865356
TI  - [Surgical options for obesity: results and complications].
AB  - Conservative therapy results almost always in failure in the morbidly obese
      patient. Bariatric surgery is currently the only treatment associated with
      sufficient and sustained weight loss. The role of obesity surgery has markedly
      increased since the development of laparoscopic techniques. Proximal gastric
      bypass is currently the procedure of choice. It is followed by an excess weight
      loss of approximately 60-70%, and is effective in over 80% of the patients. In
      Switzerland, access to surgery is limited to patients with a BMI >40 kg/m2.
      Preoperative evaluation is of paramount importance, and so is patient instruction
      and teaching before surgery. After bariatric surgery, life-long follow-up by a
      specialized team is essential.

PMID- 15865357
TI  - [Impact of bariatric surgery on health and quality life of obese patients].
AB  - The important weight loss due to bariatric surgery allows to improve and even
      correct, a great part of the comorbidities induced by obesity, as well as quality
      of life, and to reduce the coming out of cardiovascular and metabolic diseases in
      operated patients. The impact of surgical treatment on the patient's health and
      quality of life also allows to reduce direct and indirect costs of morbid
      obesity. However, its effects on mortality have not yet been clearly proved. The
      preoperative evaluation and the long term follow-up by a skilled team are
      essential to reduce potential complications, especially on the nutritional field
      and the risks of recovered weight linked to binge eating disorders.

PMID- 15865358
TI  - [Painful total hip arthroplasty].
AB  - The results of the total hip prostheses in terms of cost-efficiency make one of
      the surgical procedures the most efficient. Usually, the articular pains
      disappear completely and the patient function improves. Outside, turned out
      failures, which require a revision, some patients present residual pain
      persisting after the intervention or appearing secondarily. Considering the
      important number of total hip arthroplasties, this clinical situation is not so
      rare and the generalist, as the specialist, can be confronted there. The
      experience shows that the surgical revisions, in the absence of a precise
      diagnosis are disappointing and often do not improve the patient. This article
      presents the diagnostic and therapeutic steps advised to face this problem.

PMID- 15865359
TI  - [Otorhinolaryngologic cancer].

PMID- 15865360
TI  - [Electrocardiography in the elderly].

PMID- 15865361
TI  - [The deceptive myth of clinical experience].

PMID- 15865362
TI  - [What will become of Intrinsa?].

PMID- 15865363
TI  - [Colon cancer: a new French medical problem?].

PMID- 15865364
TI  - Apparent causality paradox in frustrated Gires-Tournois interferometers.
AB  - Negative group delay times upon total reflection from frustrated Gires-Tournois
      interferometers seem to violate causality. Contrary to what has been recently
      argued in the literature, I show with the example of total light reflection upon
      an ideal nonabsorbing plasma that adding the time associated with the Goos
      Hanchen shift does not solve the paradox, which remains open.

PMID- 15865365
TI  - Characterization of the performance of optical amplitude-shift keying
      differential phase-shift keying orthogonally modulated signals.
AB  - We analytically investigate the signal performance of orthogonal modulation with
      slow amplitude-shift keying (ASK) data superimposed upon a high-speed
      differential phase-shift keying (DPSK) signal. The receiver sensitivities for
      both the ASK and the demodulated DPSK signals are formulated based on a
      probability model, and their dependence on the bit rate and the extinction ratio
      of the ASK data is theoretically investigated. A simple result of analysis of
      DPSK data performance has been derived. We verified the analytical results by
      experimental measurements.

PMID- 15865366
TI  - Intrapulse depolarization in optical fibers: a classical analog of spin
      decoherence.
AB  - We show that the combination of cross-phase modulation and polarization-mode
      dispersion inside optical fibers leads to a novel phenomenon of intrapulse
      depolarization manifested as different random states of polarization across the
      pulse profile. Such polarization evolution of optical pulses is directly
      analogous to the phenomenon of spin decoherence in semiconductors or pseudospin
      relaxation in atoms.

PMID- 15865367
TI  - High group birefringence in air-core photonic bandgap fibers.
AB  - A numerical investigation of group birefringence is carried out on a recently
      reported highly birefringent hollow-core photonic bandgap fiber by use of an
      efficient vector finite-element method. The hollow fiber core has an area as
      large as that of approximately four airholes in the cladding region and assumes a
      rhombic shape with round corners, and the airholes in the cladding region are
      hexagonal and provide a high air-filling fraction. Numerical results show very
      high group birefringence of the order of 10(-2) and phase birefringence of the
      order of 10(-3).

PMID- 15865368
TI  - Effect of optical phase on a distributed Brillouin sensor at centimeter spatial
      resolution.
AB  - Because of the power imbalance between the two arms of an interferometer in an
      electro-optic modulator (EOM), the output of the EOM is combined amplitude
      modulation (AM) and phase modulation (PM) for the probe signal consisting of the
      pulse and the dc component. Because of this PM, the Brillouin gain-loss spectrum
      becomes asymmetric. The central Brillouin frequency is shifted from that of an AM
      pulse. The maximum extinction ratio of the EOM is limited to approximately 29 dB
      for a power-splitting ratio of 51% to 49%. The asymmetric property induced by PM
      is not pulse shape dependent; for both Gaussian- and super-Gaussian-shaped pulses
      the Brillouin loss spectrum is symmetric for AM and asymmetric for combined AM
      and PM (power imbalance).

PMID- 15865369
TI  - Nonlinear propagation effects in antiresonant high-index inclusion photonic
      crystal fibers.
AB  - We experimentally and numerically investigate femtosecond-pulse propagation in a
      microstructured optical fiber consisting of a silica core surrounded by airholes
      that are filled with a high-index fluid. This fiber combines the resonant
      properties of hollow-core bandgap fibers and the high nonlinearity of index
      guiding waveguides. A range of nonlinear optical effects can be observed,
      including soliton propagation, dispersive wave generation, and a Raman self
      frequency shift. Tuning the center wavelength of the laser and varying the
      refractive index of the fluid lead to different propagation effects, mediated by
      the strongly wavelength-dependent group-velocity dispersion in these photonic
      bandgap confining structures.

PMID- 15865370
TI  - Wave-front reconstruction from a sequence of interferograms recorded at different
      planes.
AB  - We present a method by which the phase and the amplitude of a wave front are
      obtained by processing a sequence of intensity patterns recorded at different
      planes. We do not use any reference wave, as one does for holography. Simulations
      and experimental results are presented.

PMID- 15865372
TI  - Holographic manipulation of nanoparticle distribution morphology in nanoparticle
      dispersed photopolymers.
AB  - We report on experimental verification of mass transfer of nanoparticles during
      holographic recording in nanoparticle-dispersed photopolymers. Through direct
      observations of the microscopic structure of recorded holograms as well as
      optical measurements of the phase shift between the light interference pattern
      and a recorded hologram we find that holographic exposure causes nanoparticles to
      be redistributed from bright to dark regions, leading to periodic assembly of
      nanoparticles and thereby to formation of high-contrast holograms.

PMID- 15865371
TI  - Compact Fourier-transform volume holographic spectrometer for diffuse source
      spectroscopy.
AB  - We present a new idea for diffuse source spectroscopy using a Fourier-transform
      volume holographic spectrometer formed by a Fourier-transform lens, a volume
      hologram, and a CCD. We show that this spectrometer can operate well under
      spatially incoherent light illumination. Furthermore, this spectrometer is less
      bulky, less sensitive to input alignment, and potentially more appropriate for
      implementation of highly sensitive spectrometers than conventional spectrometers.

PMID- 15865373
TI  - Absolute frequency measurement of rubidium 5S-7S two-photon transitions with a
      femtosecond laser comb.
AB  - The absolute frequencies of rubidium 5S-7S two-photon transitions at 760 nm are
      measured to an accuracy of 20 kHz with an optical frequency comb based on a mode
      locked femtosecond Ti:sapphire laser. The rubidium 5S-7S two-photon transitions
      are potential candidates for frequency standards and serve as important optical
      frequency standards for telecommunication applications. The accuracy of the
      hyperfine constant of the 7S1/2 state is improved by a factor of 5 in comparison
      with previous results.

PMID- 15865374
TI  - Stratified waveguide grating coupler for normal fiber incidence.
AB  - We propose a new stratified waveguide grating coupler (SWGC) to couple light from
      a fiber at normal incidence into a planar waveguide. SWGCs are designed to
      operate in the strong coupling regime without intermediate optics between the
      fiber and the waveguide. Two-dimensional finite-difference time-domain simulation
      in conjunction with microgenetic algorithm optimization shows that approximately
      72% coupling efficiency is possible for fiber (core size of 8.3 microm and
      delta=0.36%) to slab waveguide (1.2-microm core and delta=3.1%) coupling. We show
      that the phase-matching and Bragg conditions are simultaneously satisfied through
      the fundamental leaky mode.

PMID- 15865375
TI  - Creation of a three-dimensional optical chain for controllable particle delivery.
AB  - We propose a design for producing a conveyable quasi-periodic optical chain that
      can stably trap and deliver multiple individual particles in three dimensions at
      different planes near the focus. A diffractive optical element (DOE) is designed
      to spatially modulate the phase of an incoming radially polarized beam. For a
      tighly focused beam, a three-dimensional (3D) optical chain can be formed because
      of the difference in the Gouy phase shift from two concentric regions of the DOE.
      A desired number of particles can be stably tweezed one by one with individual 3D
      volumes in this trapping structure. By controlling the phase modulation of the
      incident beam, one can manipulate the interference pattern to accelerate and
      transport trapped particles along the optical axis in a prescribed way.

PMID- 15865376
TI  - Near-infrared laser operation of Cr3+ centers in chromium-doped LiInGeO4 and
      LiScGeO4 crystals.
AB  - Laser action has been demonstrated in two new tunable Cr3+-doped crystals.
      Absorption, emission, and excitation measurements for various crystal
      orientations have been performed for chromium-doped LiInGeO4 and LiScGeO4 single
      crystals. From the spectroscopic measurements, two optical active centers were
      identified: tetrahedrally coordinated Cr4+ and octahedrally coordinated Cr3+.
      Gain-switched, tunable laser operation of Cr3+ centers has been demonstrated in
      both crystals. An ultrawide tuning range from 1150 to 1480 nm for LiInGeO4 and
      1220-1380 nm for LiScGeO4 has been achieved. To our knowledge this is the widest
      bandwidth and the most near-infrared shifted wavelength range for lasing ever
      demonstrated for Cr3+ ions.

PMID- 15865377
TI  - Widely tunable 1.94-microm Tm:BaY2F8 laser.
AB  - A novel BaY2F8 crystal doped with thulium ions is grown and extensively
      investigated. Owing to the large number of vibronic levels and to a favorable
      electron-phonon coupling, extremely wide absorption and emission bands around 1.9
      microm are observed. A room-temperature Tm:BaY2F8 laser tunable over a 210-nm
      interval, from 1849 to 2059 nm, is demonstrated.

PMID- 15865378
TI  - Diode-pumped continuous-wave and femtosecond laser operations of a
      heterocomposite crystal Yb3+: SrY4(SiO4)3O parallel Y2Al5O12.
AB  - We report cw and femtosecond laser operations under diode pumping of a diffusion
      bonding heterocomposite Yb-doped crystal: Yb3+:SrY4(SiO4)3O parallel Y2Al5O12(YAG
      paralell SYS:Yb). To show the advantages of this heterocomposite crystal over
      classical Yb:SYS crystal, we first investigate the high-power cw regime. A cw
      power of 4.3 W is demonstrated. The femtosecond regime is also investigated, and
      1-W-average-power, 130-fs pulses at 1070 nm are produced, which represents, to
      our knowledge, the first demonstration of an Yb-doped heterocomposite mode-locked
      laser.

PMID- 15865379
TI  - Intensity-modulating characteristics of a laser diode subjected to optical
      injection.
AB  - We have found that the optical power of a laser diode (LD) does not change with
      the injected light intensity that is modulated when its injection current is at
      some specific values. The amplitude of optical power change of the LD varies
      periodically with the increase of the injection current. It is made clear through
      theoretical analysis that these phenomena are caused by gain compression and
      interband carrier absorption of the LD that depend on longitudinal mode
      competition, bandgap-shrinkage effects, thermal conduction, and so on. Our
      experimental results make it easy to eliminate optical power change of LDs. We
      only need to choose a proper value of the injection current.

PMID- 15865380
TI  - Circularly polarized optical spatial solitons.
AB  - We present, experimentally and theoretically, a polymer material system that
      supports optical spatial solitons of circular polarization. We demonstrate one
      dimensional circularly polarized dark solitons supported by photoisomerization
      nonlinearity in a bulk polymer.

PMID- 15865381
TI  - Characterization of a second-order nonlinear layer profile in thermally poled
      optical fibers with second-harmonic microscopy.
AB  - Second-harmonic microscopy has been successfully applied to characterize the
      second-order nonlinear layer in optical fibers thermally poled at 280 degrees C
      and 3.5 kV for 30 min. The nonlinear layer was found to be approximately 5.1
      microm deep under the anode and was not always centered about the closest point
      between the electrodes.

PMID- 15865382
TI  - Nonlinear photonic lattices in anisotropic nonlocal self-focusing media.
AB  - We analyze theoretically and generate experimentally two-dimensional nonlinear
      lattices with periodic phase modulation in a photorefractive medium. The light
      induced periodically modulated nonlinear refractive index is highly anisotropic
      and nonlocal, and it depends on the lattice orientation relative to the crystal
      axis. We discuss the stability of such induced photonic structures and their
      guiding properties.

PMID- 15865383
TI  - Fano resonance in quadratic waveguide arrays.
AB  - We study resonant light scattering in arrays of channel optical waveguides in
      which tunable quadratic non-linearity is introduced as nonlinear defects by
      periodic poling of single (or several) waveguides in the array. We describe novel
      features of wave scattering that can be observed in this structure and show that
      it is a good candidate for observation of Fano resonance in nonlinear optics.

PMID- 15865384
TI  - Determination of optical Kerr nonlinearity of a photonic bandgap structure by Z
      scan measurement.
AB  - Through analysis of the dispersion relation in a photonic bandgap structure, the
      effective optical Kerr nonlinearity that determines a Z-scan profile particularly
      near the stop-band edges, is derived. Near and inside the stop band, the
      nonlinear optical phase change that originates from an off-resonant response is
      converted into a change in nonlinear optical intensity through Bragg reflection.
      The Z-scan measurement of a cholesteric liquid-crystal photonic bandgap structure
      confirmed that off-resonant Kerr nonlinearity is responsible for the
      characteristic open-aperture Z-scan profiles near the stop-band edges.

PMID- 15865385
TI  - Improvement of the optical signal-to-noise ratio in common-path holographic
      storage by use of a polarization-controlling media structure.
AB  - A holographic storage arrangement with common-path optics is likely to suffer
      from degradation of the optical signal-to-noise ratio (SNR) owing to scattering
      of the reference beam. Instead of the conventional method of spatial separation
      between the reference beam and a reconstruction beam, adoption of a combined
      spatial and polarization separation is proposed. To achieve polarization
      separation by using a photopolymer as the recording material, a media structure
      including retardation films and a reflection layer is proposed such that the
      polarization states of the two beams are the same inside the material but
      orthogonal outside. Preliminary experiments to show the feasibility of this idea
      for improving optical SNR are also demonstrated.

PMID- 15865386
TI  - Direct laser writing defects in holographic lithography-created photonic
      lattices.
AB  - As a well-established laser fabrication approach, holographic lithography, or
      multibeam interference patterning, is known for its capability to create long
      range ordered large-volume photonic crystals (PhCs) rapidly. Its broad use is,
      however, hampered by difficulty in inducing artificially designed defects for
      device functions. We use pinpoint femtosecond laser ablation to remove and two
      photon photopolymerization to add desired defective features to obtain photonic
      acceptors and photonic donors, respectively, in an otherwise complete PhC matrix
      produced by holographic lithography. The combined use of the two direct laser
      writing technologies would immediately make holographic lithography a promising
      industrial tool for PhC manufacture.

PMID- 15865387
TI  - Surface plasmon rainbow jets.
AB  - A new method for optically exciting and visualizing surface plasmons in thin
      metal films is described. The technique relies on the use of a high-numerical
      aperture objective lens to locally launch a broad wavelength spectrum of surface
      waves and to detect the leaky radiative modes associated with them. We used this
      approach to obtain a direct visualization of the plasmon intensity distributions,
      e.g., rainbow jets, and to quantify their propagation lengths throughout the
      visible spectrum.

PMID- 15865388
TI  - All-optical passive transistor.
AB  - We show the possibility of developing an all-optical passive transistor in a
      simple and novel way. This could be done by copropagating two coaxial beams
      through a modified optical power filter. We show NOT logic and intensity
      modulation of the strong beam by the weak beam obtained with the analog.

PMID- 15865389
TI  - Accurate lidar temperatures with narrowband filters.
AB  - At daytime, metal resonance lidars need narrowband spectral filtering in the
      receiver to measure Doppler temperatures in the mesopause region. For our K lidar
      equipped with a Faraday anomalous dispersion optical filter we demonstrate that
      the derived resonance temperatures can be shifted by 10 K because of the
      wavelength dependence of the filter transmission for the Rayleigh scattered light
      when this filter transmission is used for normalization. We show that, if all
      filter effects are considered correctly, temperature measurements at daytime can
      be as accurate as at nighttime without such filters.

PMID- 15865390
TI  - Dielectric optical elements for surface plasmons.
AB  - Basic optical elements for surface plasmons are fabricated and their
      functionality (focusing, refraction, and total internal reflection) is
      demonstrated experimentally. The optical elements consist of dielectric
      structures of defined geometry on top of a gold film. The working principle of
      these structures is discussed on the basis of calculated surface plasmon
      dispersion relations.

PMID- 15865391
TI  - Design of a monolithic piezoelectrically actuated microelectromechanical tunable
      vertical-cavity surface-emitting laser.
AB  - We report the design of a monolithic piezoelectrically actuated
      microelectromechanical tunable vertical-cavity surface-emitting laser (VCSEL).
      The main advantages of piezoelectric actuation compared with conventional
      capacitive techniques are improved wavelength control, reduced external and tilt
      losses, and lower power supply voltages. The details of the piezoelectric
      actuation scheme for a 980-nm VCSEL with a variable air gap are described. A
      tuning range of approximately 35 nm can theoretically be achieved with a 3-V
      power supply (2 x reduction from that of electrostatic actuation) by use of a 250
      microm-long cantilever beam. The proposed actuation mechanism is insensitive to
      the pull-in phenomenon, therefore improving wavelength control and reducing
      threshold current. Drastic improvements in power efficiency make it ideal for low
      power applications such as all-optical communication, chip-scale atomic clocks,
      and biological studies.

PMID- 15865392
TI  - Opposite Goos-Hanchen shifts for transverse-electric and transverse-magnetic
      beams at the interface associated with single-negative materials.
AB  - Goos-Hanchen shifts are investigated when total reflection occurs at the
      interfaces associated with single-negative materials (SNMs). A general rule for
      judging the direction of the Goos-Hanchen lateral shift concerning lossless media
      is obtained: Whether the lateral shift is positive or negative depends on the
      sign of micro1micro2 for TE-polarized incident beams and epsilon1epsilon2 for TM
      polarized incident beams. It was theoretically demonstrated that, at the
      interface associated with SNMs, TE- and TM-polarized incident beams experience
      opposite Goos-Hanchen lateral shifts. An effective and simple approach to
      discriminating epsilon-negative material and micro-negative material is proposed.

PMID- 15865393
TI  - Quantitative analysis of depolarization of backscattered light by stochastically
      inhomogeneous dielectric particles.
AB  - We determine the relationship between the depolarization properties of
      inhomogeneous particles and the statistical parameters of their internal
      refractive-index distributions. Our analysis demonstrates that the linear
      depolarization ratio of backscattered light by an inhomogeneous particle is
      approximately proportional to both the squared standard deviation and the squared
      correlation length of the particle's internal refractive-index distribution. We
      verify this result by conducting rigorous numerical studies using the finite
      difference time-domain method. This improved understanding of light
      depolarization by inhomogeneous structures may enhance polarization-based
      biomedical optical imaging techniques.

PMID- 15865394
TI  - Dynamical hysteresis in a three-level atomic system.
AB  - We have experimentally investigated dynamical hysteresis behavior by changing the
      sweeping frequency of the cavity input field in the optical bistability of
      rubidium atoms (in a three-level atomic-type configuration) inside an optical
      cavity. The shape, width (or area), and direction of the hysteresis cycle are
      sensitive functions of the sweeping frequency for such an optical bistable
      system.

PMID- 15865395
TI  - Measurement of the spectral properties of the two-photon state generated via type
      II spontaneous parametric downconversion.
AB  - We report complete measurement of the spectral properties of photon pairs
      generated via spontaneous parametric downconversion. The measurements, which
      include not only single-photon spectra but also two-photon joint spectra, were
      performed for both cw and ultrafast-pumping configurations. In agreement with
      theoretical predictions, the spectra for the ultrafast-pumped case reveal
      asymmetries that are not present with cw pumping.

PMID- 15865396
TI  - Fourier transform measurement of two-photon excitation spectra: applications to
      microscopy and optimal control.
AB  - We report a novel Fourier transform method for measuring two-photon excitation
      spectra. We demonstrate this method using simple dye molecules and discuss its
      applications in two-photon fluorescence microscopy and optimal control. This
      method facilitates an intuitive interpretation of recent control experiments in
      terms of tuning the nonlinear spectrum of the exciting laser source.

PMID- 15865397
TI  - Thin-film spatial filters.
AB  - A thin-film optical filter used as a one-dimensional spatial filter is presented,
      and its design is briefly examined. The filter consists of a stack of quarter
      wave dielectric layers upon a right-angle prism that selectively cancel a
      reflected or transmitted plane-wave front for various angles of incidence.
      Transmittance and reflectance are low-pass functions or high-pass functions of
      the angle of incidence with a high degree of steepness. In combination, these
      filters exhibit bandpass transmittance with a variable bandwidth. Applications to
      detection of extrasolar planets are briefly discussed.

PMID- 15865398
TI  - Chirp-induced dynamics of femtosecond filaments in air.
AB  - We investigate the influence of a chirped phase on femtosecond pulses propagating
      in air. Pulses with an initially negative chirp are temporally compressed by
      compensation with group-velocity dispersion. We demonstrate that this property,
      combined with plasma defocusing, can be used to trigger filamentation at
      different foci, increase self-guiding ranges, or even shorten pulse duration.

PMID- 15865399
TI  - 10(-10) temporal contrast for femtosecond ultraintense lasers by cross-polarized
      wave generation.
AB  - We take advantage of nonlinear properties associated with chi(3) tensor elements
      in BaF2 cubic crystal to improve the temporal contrast of femtosecond laser
      pulses. The technique presented is based on cross-polarized wave (XPW)
      generation. We have obtained a transmission efficiency of 10% and 10(-10)
      contrast with an input pulse in the millijoule range. This filter does not affect
      the spectral shape or the phase of the cleaned pulse. It also acts as an
      efficient spatial filter. In this method the contrast enhancement is limited only
      by the extinction ratio of the polarization discrimination device.

PMID- 15865400
TI  - Double chirped-pulse-amplification laser: a way to clean pulses temporally.
AB  - We demonstrate a double chirped-pulse-amplification (CPA) Ti: sapphire laser
      system that includes two CPA stages with intermediate nonlinear temporal pulse
      filtering. The method makes it possible to reduce substantially the background of
      amplified spontaneous emission (ASE), including prepulses and postpulses. An ASE
      temporal contrast of 10(10) was demonstrated at 20 mJ of output energy and 50-fs
      pulse duration. The demonstrated scheme is applicable to petawatt power-level
      laser systems.

PMID- 15865401
TI  - Impulsive stimulated Raman scattering: comparison between phase-sensitive and
      spectrally filtered techniques.
AB  - Impulsive stimulated Raman scattering is used to generate and control coherent
      phonons and other low-frequency modes. In transparent materials, pump-probe
      experiments are usually performed by spectrally resolving the probe beam and
      measuring the spectral shift as a function of pump-probe time delay. By measuring
      the optical phase of the probe pulse as a function of time delay, we find that
      the phonon signal can be increased by a factor alpha(omegadelta)(-1), where omega
      is the phonon frequency and delta is the pulse duration.

PMID- 15865402
TI  - Continuous wavelength-tunable optical short-pulse generation by use of two Fabry
      Perot laser diodes in a mutual injection-seeding scheme.
AB  - A simple system for producing continuous and widely wavelength-tunable optical
      short pulses in a mutual injection-seeding scheme is presented. The system
      exhibits a good side-mode suppression ratio of greater than 32.7 dB over a large
      wavelength tuning range of 33.8 nm. The system is easy to operate and convenient
      for continuous wavelength tuning.

PMID- 15865403
TI  - Stabilized frequency comb with a self-referenced femtosecond Cr:forsterite laser.
AB  - A frequency comb is generated with a Cr:forsterite femtosecond laser, spectrally
      broadened through a highly nonlinear optical fiber to span from 1.0 to 2.2 ,m,
      and stabilized using the f-to-2f self-referencing technique. The repetition rate
      and the carrier-envelope offset frequency are stabilized to a hydrogen maser,
      calibrated by a cesium atomic fountain clock. Simultaneous frequency measurement
      of a 657-nm cw laser by use of the stabilized frequency combs from this
      Cr:forsterite system and a Ti:sapphire laser agree at the 10(-13) level. The
      frequency noise of the comb components is observed at 1064, 1314, and 1550 nm by
      comparing the measured beat frequencies between cw lasers and the supercontinuum
      frequency combs.

PMID- 15865404
TI  - Changes in carboxypeptidase A, dipeptidase and Na+/K+ ATPase activities in the
      intestine of rats orally exposed to different doses of cadmium.
AB  - The purpose of the present study was to evaluate the effect of cadmium on some
      protein digestive and absorption enzymes in rats. Thirty-six rats were grouped
      into three groups of 12 animals each; one group received deionised water and
      acted as control. One group received 445 microM Cd and the last group received
      890 microM Cd in their drinking water for a period of one month. The results
      obtained indicate that increasing the level of cadmium from 445 microM to 890
      microM in the drinking water of the rats led to 29% and 23% increase in
      accumulated cadmium in the proximal and distal small intestine respectively. The
      body weight gain of rats exposed to 445 microM and 890 microM Cd was decreased by
      about 24% and 43% respectively when compared with the control. The activities of
      carboxypeptidase A, dipeptidase and Na+/K+ ATPase were reduced in the mucosa of
      the proximal end of the small intestine of cadmium exposed rats. The reduction
      was dose dependent; with the 890 microM Cd exposed rats displaying the least
      activities. In the distal small intestine, the activities of these enzymes were
      restored in the 445 microM Cd exposed rats to levels that were not statistically
      different (P > 0.05) from those observed in the controls. In the 890 microM Cd
      exposed rats, dipeptidase activity improved by about 80% compared with the
      activity of the enzyme in the proximal small intestine. Likewise, Na+/K+ ATPase
      activity increased by about 125% compared with the observed level in the proximal
      small intestine. The study suggests that cadmium given to rats in drinking water
      compromise protein digestion and absorption of nutrients particularly in the
      proximal region of small intestine and could account for weight reduction
      associated with cadmium toxicity.

PMID- 15865405
TI  - Nickel exposure and its effects.
AB  - The aim of the study was to determine the nickel concentrations of soil and plant
      specimens taken from a rural area exposed to cement factory emissions and also to
      determine the blood concentrations and sensitivity conditions observed in humans
      residing in this rural area. The study was carried out in Cukurhisar, a town in
      Eskisehir-Turkey, between May 2000 and March 2001. Beside the 108 soil (36 for
      control) and plant specimens, which were taken from 8 directions from the cement
      factory, blood samples of the individuals residing in this area were taken from
      258 subjects (258 for control) following a physical examination, and patch tests
      were also applied. The nickel concentrations of the soil and plant specimens
      taken from different places in different directions of the factory were higher
      than in the control areas. The physical examination of subjects did not reveal
      results different from those of the control group except for the diagnosis of
      contact dermatitis. The analyses of venous blood samples showed that nickel
      concentrations were found to be within the reference values given for both
      groups, but higher in the subjects (p < 0.001). According to the results of patch
      tests, sensitivity to nickel was found to be more frequent for the subject group
      than the control group (p < 0.05). According to these results, clinical tools
      revealed no toxic effects for the subjects, except contact dermatitis. However,
      sensitivity to patch tests showed that this subject group has been affected
      compared to the control group and that this effect increased with age.

PMID- 15865406
TI  - Light-harvesting properties of zinc complex of chlorophyll-a from spirulina in
      surfactant micellar media.
AB  - Zn chlorophyll-a was prepared from Mg chlorophyll-a from spirulina and the
      optical properties of the ground state and the photoexited state of Zn
      chlorophyll-a in aqueous surfactant micellar media were studied using UV-vis
      absorption, fluorescence emission spectra, electrochemical and fluorescence
      lifetime measurements. In comparison of the UV-vis absorption and fluorescence
      emission spectra of Zn chlorophyll-a and Mg chlorophyll-a, the blue-shift in the
      absorption bands and emission peak of Zn chlorophyll-a was observed. The energies
      of the first excited singlet state of Zn chlorophyll-a was 1.87 eV. The first
      oxidation and reduction potentials of the photoexcited singlet state of Zn
      chlorophyll-a were -0.67 and 0.60 V, respectively. Fluorescence lifetime of Zn
      chlorophyll-a was 9.0 ns in CTAB micellar solution. The fluorescence lifetime of
      Zn chlorophyll-a is shorter than that of Mg chlorophyll-a (9.8 ns). The
      photositability of Zn chlorophyll-a was superior to that of Mg chlorophyll-a in
      various pH conditions.

PMID- 15865407
TI  - Changes of chromium behavior in soil during phenanthrene removal by Penicillium
      frequentans.
AB  - Soil contamination due to polycyclic aromatic hydrocarbons is often associated
      with the presence of high levels of potentially toxic metals. Bioremediation is
      an important option for the clean up of this type of contamination. Changes of
      chromium fluxes and concentrations during the phenanthrene removal by Penicillium
      frequentans in soil were investigated. During the bioremediation process, changes
      in chromium behavior were monitored by Diffusive Gradients in Thin-films (DGT)
      and by filtration in both sterilized and non-sterilized soils. DGT provided
      absolute data on fluxes from the solid phase and relative trends of
      concentrations of the most labile metal species. Filtration provided data on the
      concentrations of Cr in the solution phase. Together the data provided
      information about the physical and chemical metal behavior. Results showed that
      the highest phenanthrene removal was observed in non-sterilized soil (which
      included the autochthonous microorganisms and P. frequentans inoculum), with a
      phenanthrene removal of 73 +/- 3.2%. However, in all cases microbial activity
      increased chromium fluxes and chromium soil solution concentration. The
      bioremediation of soil by P. frequentans increased the lability and mobility of
      chromium in soil, with potential consequences for plant uptake and for increased
      movement of metals into the human food chain.

PMID- 15865408
TI  - The function of Alr1p of Saccharomyces cerevisiae in cadmium detoxification:
      insights from phylogenetic studies and particle-induced X-ray emission.
AB  - Two genes in Saccharomyces cerevisiae, ALR1 and ALR2, encode transmembrane
      proteins involved in Mg2+ uptake. The present study investigates the phylogenetic
      relationship of Alr1p/Alr2p with bacterial CorA proteins and some proteins
      related to Mg2+ influx/efflux transport in mitochondrial and bacterial zinc
      transporters; including hydrophobic cluster analysis (HCA). The phylogenetic
      results indicate that the Alrp sequences of S. cerevisiae share a common carboxy
      terminus with proteins related to zinc efflux transport. We also analyse the
      intracellular metal content by particle-induced X-ray emission (PIXE) after cell
      exposure to cadmium. The PIXE analysis of cadmium-exposed ALR mutants and wild
      type yeast cells suggests that Alrp has a central role in cell survival in a
      cadmium-rich environment.

PMID- 15865409
TI  - Voltammetric studies of Zn and Fe complexes of EDTA: evidence for the push
      mechanism.
AB  - The 'push' hypothesis for the antioxidant action of Zn2+ is based on its
      displacement of iron from a low molecular weight pro-oxidant complex. In this
      study, the chemical plausibility of that proposed function is investigated by
      cyclic voltammetry. As a model for a pro-oxidative low molecular weight iron
      complex the Fe(II/III)/EDTA couple was examined. This complex was selected for
      its well-defined electrochemical, iron stability constants, and similarity to
      other low molecular weight chelates in physiological fluids in terms of logical
      binding sites, i.e. amino, and carboxylate groups. Also investigated were iron
      complexes of nitrilotriacetic acid and DL-glutamic acid. Results demonstrate that
      approximately 90% of the cyclic voltammetric peak current for Fe(III)EDTA
      reduction and the EC' current for the mediated reduction of H2O2 by
      Fe(II/III)EDTA (Fenton Reaction) are lost when Zn2+ is introduced to a 1:1 molar
      ratio relative to iron. All experiments were conducted in HEPES buffered
      solutions at pH 7.4. Iron (II/III) complexes of nitrilotriacetic acid and DL
      glutamic acid followed the same trends. Cyclic voltammetric experiments indicate
      that Zn2+ displaces Fe(III) from EDTA despite the much larger stability constant
      for the iron complex (10(25.1)) versus zinc (10(16.50)). The hydrolysis aided
      displacement of Fe(III) from EDTA by Zn2+ is considered by the equilibria
      modeling program, HySS. With Fe(III) hydrolysis products included, Zn2+ is able
      to achieve 90% displacement of iron from EDTA, a result consistent with cyclic
      voltammetric observations.

PMID- 15865410
TI  - The determination of ferric iron in plants by HPLC using the microbial iron
      chelator desferrioxamine E.
AB  - Common methods for plant iron determination are based on atomic absorption
      spectroscopy, radioactive measurements or extraction with subsequent
      spectrophotometry. However, accuracy is often a problem due to background,
      contamination and interfering compounds. We here describe a novel method for the
      easy determination of ferric iron in plants by chelation with a highly effective
      microbial siderophore and separation by high performance liquid chromatography
      (HPLC). After addition of colourless desferrioxamine E (DFE) to plant fluids, the
      soluble iron is trapped as a brown-red ferrioxamine E (FoxE) complex which is
      subsequently separated by HPLC on a reversed phase column. The formed FoxE
      complex can be identified due to its ligand-to-metal charge transfer band at 435
      nm. Alternatively, elution of both, DFE and FoxE can be followed as separate
      peaks at 220 nm wavelength with characteristic retention times. The
      extraordinarily high stability constant of DFE with ferric iron of K = 10(32)
      enables extraction of iron from a variety of ferrous and ferric iron compounds
      and allows quantitation after separation by HPLC without interference by coloured
      by-products. Thus, iron bound to protein, amino acids, citrate and other organic
      acid ligands and even insoluble ferric hydroxides and phosphates can be
      solubilized in the presence desferrioxamine E. The "Ferrioxamine E method" can be
      applied to all kinds of plant fluids (apoplasmic, xylem, phloem, intracellular)
      either at physiological pH or even at acid pH values. The FoxE complex is stable
      down to pH 1 allowing protein removal by perchloric acid treatment and HPLC
      separation in the presence of trifluoroacetic acid containing eluents.

PMID- 15865411
TI  - Synthesis and properties of different metal complexes of the siderophore
      desferriferricrocin.
AB  - Desferriferricrocin is a cyclic hexa-peptide siderophore with three hydroxamates
      as primary coordination groups. It forms metal complexes with Fe(III), Cr(III),
      Al(III), Ga(III), Cu(II), and Zn(II). These complexes were prepared and
      characterized using UV-vis, circular dichroism spectroscopy (CD), nuclear
      magnetic resonance spectroscopy (NMR), and electrospray ionization mass
      spectroscopy (ESI-MS). The mononuclear trivalent metal complexes of
      desferriferricrocin were stable in aqueous solutions, and their coordination
      centers primarily adopted the lambda configuration. The formation of multinuclear
      complexes of desferriferricrocin was determined by ESI-MS. Desferriferricrocin
      was able to bind up to three Cu(II) and two Zn(II) respectively. Heteronuclear
      complexes containing one trivalent and one divalent were also determined. In
      these complexes, amide nitrogens were utilized as alternative binding groups of
      desferriferricrocin in addition to the primary binding groups, the hydroxamates.

PMID- 15865412
TI  - The configuration of the chiral carbon atoms in staphyloferrin A and analysis of
      the transport properties in Staphylococcus aureus.
AB  - Staphyloferrin A, the iron-transporting siderophore of Staphylococci, contains
      two citric acid residues linked to a D-ornithine backbone, having thus three
      chiral centers. While the chirality of the backbone can be determined after
      hydrolysis, the chirality of the two citryl residues can only be determined from
      the intact staphyloferrin A molecule by circular dichroism spectra. The chirality
      of the quarternary carbon atoms of citryl residues in fungal rhizoferrin and
      bacterial enantio-rhizoferrin have been determined previously to be R,R and S,S
      respectively. The present investigation shows that of the three chiral centers in
      staphyloferrin A, the citryl residues can be assigned an S,S-configuration by
      comparison with synthetic analogs, confirming a common chirality among the
      bacterial enantio-rhizoferrin and staphyloferrin A. This suggests that the
      bacterial carboxylates originate from a common biosynthetic pathway leading to an
      S,S-configuration, while the fungal rhizoferrin possessing an R,R-configuration
      must have a different biosynthetic origin. Growth promotion tests with
      staphylococci revealed that the S,S-configuration of staphyloferrin A and enantio
      rhizoferrin enabled iron uptake, while the fungal rhizoferrin with R,R
      configuration was not utilized.

PMID- 15865413
TI  - Whole animal copper flux assessed by positron emission tomography in the Long
      Evans cinnamon rat--a feasibility study.
AB  - Copper is an essential trace element. However, excess copper can lead to
      oxidation of biomolecules and cell damage and copper levels must be carefully
      controlled. While copper homeostasis has been studied extensively at the cellular
      level, short-term body copper fluxes are poorly understood. Here, we assessed for
      the first time the feasibility of measuring whole body copper flux by positron
      emission tomography, using 64Cu. A comparative approach comparing the Long-Evans
      cinnamon (LEC) rat to the wild type was chosen. LEC rats are an accepted model
      for Wilson disease, an inherited disorder of copper excretion in humans. In LEC
      rats as well as in Wilson patients, the copper transporting ATPase, ATP7B, is
      defective. This ATPase is primarily expressed in the liver and serves in copper
      secretion via the bile. Dysfunction of ATP7B leads to accumulation of copper in
      the liver. A control and an LEC rat were transgastrically injected with 10 microg
      of 64Cu and the copper flux followed for three hours by whole animal PET and
      concomitant collection of bile, as well as the analysis of tissue following
      tomography. As seen by PET, the administered copper was largely trapped in the
      stomach and the proximal intestine, and without a significant difference between
      control and LEC rat. Due to an insufficient dynamic range of the PET technology,
      copper which was systemically absorbed and primarily transported to the liver
      could only be followed by sampling and by beta-counting. Biliary copper excretion
      ensued after 15 min in the control rat, but was absent in the LEC rat. Biliary
      excretion reached saturation one hour after copper administration. The trapping
      of orally administered copper in the gastrointestinal tract may be an important
      mechanism to prevent copper toxicity under conditions of a sudden, excessive
      copper load, which cannot be alleviated by increased biliary secretion. This
      trapping does however limit the utility of PET to measure whole animal copper
      flux.

PMID- 15865414
TI  - Proteomic detection of changes in protein synthesis induced by lanthanum in BGC
      823 human gastric cancer cells.
AB  - There is increasing interest in the use of rare earth elements in medicine.
      However, the biological mechanism of action of this metal ion remains unclear. In
      the present study, changes in protein synthesis induced by lanthanum in BGC-823
      human gastric cancer cells were investigated. The proteins were separated using
      two-dimensional polyacrylamide gel electrophoresis and four proteins were
      significantly affected by lanthanum treatment when compared to an untreated
      control. Among them, one was down-regulated and three were up-regulated. Of
      these, three were successfully identified as RHOJ, CSP6 and MPI2 with peptide
      mass fingerprinting using matrix-assisted laser desorption/ionization time of
      flight mass spectrometer (MALDI-TOF-MS) after in-gel trypsin digestion. Among
      them, RHOJ was down-regulated and CSP6 and MPI2 were up-regulated. The three
      proteins are involved in various cellular functions, which are correlated with
      the regulation of cell morphology, gene transcription and cell cycle,
      respectively. It is suggested that the possible involvement of rare earth
      elements in the growth arrest of tumor cells is significantly associated with the
      differential protein expression induced by rare earth ions.

PMID- 15865415
TI  - Time dependent study to evaluate the efficacy of zinc on hepatic marker enzymes
      and elemental profile in serum and liver of protein deficient rats.
AB  - This study was designed to determine the time dependent protective effects of
      zinc sulfate on the serum and liver marker enzymes along with elemental profile
      in protein deficient Sprague Dawley (S.D.) female rats. Zinc sulfate in the dose
      of 227 mg/l in drinking water was administered to normal control as well as
      protein deficient rats for a total duration of 8 weeks. The effects of different
      treatments were studied on enzymes like alkaline phosphatase (ALP), aspartate
      aminotransferases (AST) and alanine aminotransferases (ALT) in rat serum at
      different time intervals of 1, 2, 4 and 8 weeks and in the rat liver at the end
      of study. The status of different essential elements in liver was also studied.
      The serum ALP activity got significantly depressed when estimated at the
      intervals of 4 and 8 weeks. Activity of serum ALT was significantly increased
      after 4 weeks interval in protein deficient rats and the increasing trend
      continued upto 8 weeks of protein deficiency. On the other hand, activity of AST
      showed a significant increase just after 2 weeks and activity continued to be
      increased up to 8 weeks. Moreover activities of all the hepato marker enzymes
      showed a significant increase in liver of protein deficient rats. Interestingly,
      supplementation of Zn to protein deficient rats helped in regulating the altered
      activities of ALP, AST and ALT both in serum and liver. However, zinc treatment
      alone to normal rats did not indicate any significant change in the activities of
      all the enzymes in liver as well serum except at the interval of 2 weeks where a
      marginal increase in the activity of AST was seen. It has also been observed that
      concentrations of zinc, copper, iron and selenium were found to be decreased
      significantly in protein deficient animals. However, the levels of these elements
      came back to within normal limits when zinc was administered to protein deficient
      rats.

PMID- 15865416
TI  - Divalent metal transport in the green microalga Chlamydomonas reinhardtii is
      mediated by a protein similar to prokaryotic Nramp homologues.
AB  - Information about the molecular mechanisms of metal transport in algae is scarce,
      despite the significant status these organisms have in aquatic ecosystems. In the
      present study, we describe the cloning and functional characterization of a
      divalent metal transporter (named DMT1) in the green microalga Chlamydomonas
      reinhardtii Dangeard. The longest open reading frame of the cloned DMT1 cDNA
      encodes a protein of 513 amino acids with 11 putative transmembrane domains. The
      protein belongs to the Nramp family of divalent metal transporters and shows
      surprisingly higher similarity to some prokaryotic than to eukaryotic
      polypeptides. Especially the N-terminus, which is longer than of every other
      homologue considered in this study, displays--uniquely among selected eukaryotic
      Nramps--exclusively prokaryotic characteristics. Functional complementation
      experiments in yeast strains with impaired metal transport systems, revealed that
      C. reinhardtii DMT1 has a broad specificity, acting in the transport of several
      divalent metals (manganese, iron, cadmium, copper), but excluding zinc.

PMID- 15865417
TI  - Trapping of metalloradical intermediates of the S-states at liquid helium
      temperatures. Overview of the phenomenology and mechanistic implications.
AB  - The oxygen-evolving complex (OEC) of photosystem II (PSII) consists of a Mn
      cluster (believed to be tetranuclear) and a tyrosine (Tyr Z or Y(Z)). During the
      sequential absorption of four photons by PSII, the OEC undergoes four oxidative
      transitions, S(0) to S(1), ..., S(3) to (S(4))S(0). Oxygen evolves during the
      S(3) to S(0) transition (S(4) being a transient state). Trapping of intermediates
      of the S-state transitions, particularly those involving the tyrosyl radical, has
      been a goal of ultimate importance, as that can test critically models employing
      a role of Tyr Z in proton (in addition to electron) transfer, and also provide
      important clues about the mechanism of water oxidation. Until very recently,
      however, critical experimental information was lacking. We review and evaluate
      recent observations on the trapping of metalloradical intermediates of the S
      state transitions, at liquid helium temperatures. These transients are assigned
      to Tyr Z(*) magnetically interacting with the Mn cluster. Besides the importance
      of trapping intermediates of this unique catalytic mechanism, liquid helium
      temperatures offer the additional advantage that proton motions (unlike electron
      transfer) are blocked except perhaps across strong hydrogen bonds. This paper
      summarizes the recent observations and discusses the constraints that the
      phenomenology imposes.

PMID- 15865418
TI  - A combined STD-NMR/molecular modeling protocol for predicting the binding modes
      of the glycosidase inhibitors kifunensine and salacinol to Golgi alpha
      mannosidase II.
AB  - A combined STD-NMR/molecular modeling protocol to probe the binding modes of the
      glycosidase inhibitors kifunensine and salacinol to Drosophila melanogaster Golgi
      alpha-mannosidase II (dGMII) was tested. Saturation-transfer difference (STD) NMR
      experiments were carried out for the complexes of dGMII with these two
      inhibitors. The program AutoDock 3.0 was then used to optimize the interactions
      of the inhibitors with the residues in the active site of dGMII. Theoretical STD
      effects of the ligand protons in the complexes were calculated for the different
      binding modes with the recently developed CORCEMA-ST protocol. Comparison of
      experimental and theoretical effects then permitted selection of the likely
      binding modes of the ligands. The more rigid kifunensine was used initially to
      test the protocol. Excellent correlation between experimental and theoretical
      data was obtained for one of the binding modes that also corresponded to that
      observed in the crystal structure of the complex. The protocol was then extended
      to the more flexible salacinol. For the selected binding mode, good correlation
      of experimental and theoretical data for the five-membered ring was obtained;
      however, poor correlation for protons on the acyclic chain was obtained,
      suggesting flexibility in this portion of the molecule. Comparison of the
      selected binding mode with that from a crystal structure of salacinol with dGMII
      showed excellent superimposition of the five-membered ring but another
      orientation of the acyclic chain. The results suggest that reliable structural
      binding modes of a ligand to protein in aqueous solution can be provided with the
      combined use of STD-NMR spectroscopy, molecular modeling, and CORCEMA-ST
      calculations, although highly flexible portions of the ligand may be poorly
      defined.

PMID- 15865419
TI  - Solution structure and interactions of the Escherichia coli cell division
      activator protein CedA.
AB  - CedA is a protein that is postulated to be involved in the regulation of cell
      division in Escherichia coli and related organisms; however, little biological
      data about its possible mode of action are available. Here we present a three
      dimensional structure of this protein as determined by NMR spectroscopy. The
      protein is made up of four antiparallel beta-strands, an alpha-helix, and a large
      unstructured stretch of residues at the N-terminus. It shows structural
      similarity to a family of DNA-binding proteins which interact with dsDNA via a
      three-stranded beta-sheet, suggesting that CedA may be a DNA-binding protein. The
      putative binding surface of CedA is predominantly positively charged with a
      number of basic residues surrounding a groove largely dominated by aromatic
      residues. NMR chemical shift perturbations and gel-shift experiments performed
      with CedA confirm that the protein binds dsDNA, and its interaction is mediated
      primarily via the beta-sheet.

PMID- 15865420
TI  - Peptides inducing short-lived antibody responses against Plasmodium falciparum
      malaria have shorter structures and are read in a different MHC II functional
      register.
AB  - The search for a rational method of developing an antimalarial vaccine (malaria
      caused by Plasmodium falciparum) consists of blocking receptor-ligand
      interaction. Conserved peptides derived from proteins involved in invasion and
      having strong red blood cell binding ability have thus been identified;
      immunization studies using Aotus monkeys revealed that these peptides were
      neither immunogenic nor protection-inducing. Some of these peptides induced long
      lasting and very high antibody titers and protection when their critical red
      blood cell binding residues were replaced to change their immunological
      properties. Others induced short-lived antibodies that were not associated with
      inducing protection. The three-dimensional structure of the short-lived antibody
      inducing peptide was determined by (1)H NMR. Their HLA-DRbeta1* molecule binding
      ability was also determined to ascertain the relationship among three-dimensional
      structure, their ability to bind to major histocompatibility complex class II
      molecules (MHC II), and possible short-lived antibody production. These short
      lived antibody-inducing peptides were 6.8 +/- 0.5 A shorter between those
      residues theoretically coming into contact with pocket 1 and pocket 9 of HLA
      DRbeta1* molecules to which they bind than immunogenic and protection-inducing
      peptides. These more compact alpha-helical structures suggest that these short
      lived antibody-inducing peptides could have a structure more similar to those of
      native peptides than immunogenic and protective ones. Such shortening was
      associated with a shift in HLA-DRbeta1* molecule binding and a consequent shift
      in functional register reading, mainly by alleles of the same haplotype when
      compared with immunogenic protection-inducing HABPs, suggesting an imperfect and
      different conformation of the MHC II peptide-TCR complex.

PMID- 15865421
TI  - Activity, folding, misfolding, and aggregation in vitro of the naturally
      occurring human tissue factor mutant R200W.
AB  - Tissue factor (TF), a small transmembrane receptor, binds factor VIIa (FVIIa),
      and the formed complex initiates blood coagulation by proteolytic activation of
      substrate factors IX and X. A naturally occurring mutation in the human TF gene
      was recently reported, where a single-base substitution results in an R200W
      mutation in the TF extracellular domain [Zawadzki, C., Preudhomme, C., Gaveriaux,
      V., Amouyel, P., and Jude, B. (2002) Thromb. Haemost. 87, 540-541]. This mutation
      appears to be associated with low monocyte TF expression and may protect against
      thrombosis but has not been associated with any pathological condition, and
      individuals who present the heterozygous trait appear healthy. Here, we report
      the activity, folding, and aggregation behavior of the R200W mutant of the 219
      residue soluble extracellular domain of TF (sTF(R200W)) compared to that of the
      wild-type protein (sTF(wt)). No differences in stability or FVIIa cofactor
      activity but an impaired ability to promote FX activation at physiological
      conditions between the sTF(R200W) mutant and sTF(wt) were evident. Increased
      binding of 1-anilino-8-naphthalene-sulfonic acid (ANS) to sTF(R200W) indicated a
      population of partially folded intermediates during denaturation. sTF(R200W)
      showed a dramatically increased propensity for aggregate formation compared to
      sTF(wt) at mildly acidic pHs, with an increased rate of aggregation during
      conditions, promoting the intermediate state. The lowered pH resistance could
      explain the loss of sTF(R200W) in vivo because of aggregation of the mutant. The
      intrinsic structure of the sTF aggregates appears reminiscent of amyloid fibrils,
      as revealed by thioflavin T fluorescence, atomic force microscopy, and
      transmission electron microscopy. We conclude that the lowered activity for FX
      activation and the propensity of the mutant protein to misfold and aggregate will
      both contribute to decreased coagulation activity in TF(R200W) carriers, which
      could protect from thrombotic disease.

PMID- 15865422
TI  - Structure, flexibility, and repair of two different orientations of the same
      alkyl interstrand DNA cross-link.
AB  - Interstrand DNA cross-links are the principal cytotoxic lesions produced by
      chemotherapeutic bifunctional alkylating agents. Using an N(4)C-ethyl-N(4)C
      interstrand DNA cross-link to mimic this class of clinically important cancer
      chemotherapeutic agents, we have characterized the repair, structure, and
      flexibility of DNA that contains this cross-link in two different orientations.
      Plasmid DNAs in which the cytosines of single CpG or GpC steps are covalently
      linked were efficiently processed by repair proficient and homologous
      recombination deficient strains of Escherichia coli. Repair in a nucleotide
      excision repair (NER) deficient strain was less efficient overall and displayed a
      4-fold difference between the two cross-link orientations. Both the structure and
      flexibility of DNA containing these cross-links were examined using a combination
      of (1)H NMR, restrained molecular dynamics simulations, and atomic force
      microscopy (AFM). The NMR structure of a decamer containing a CpG interstrand
      cross-link shows the cross-link easily accommodated within the duplex with no
      disruption of hydrogen bonding and only minor perturbations of helical
      parameters. In contrast, disruptions caused by the GpC cross-link produced
      considerable conformational flexibility that precluded structure determination by
      NMR. AFM imaging of cross-link-containing plasmid DNA showed that the increased
      flexibility observed in the GpC cross-link persists when it is embedded into much
      larger DNA fragments. These differences may account for the different repair
      efficiencies seen in NER deficient cells.

PMID- 15865423
TI  - Copper(II) inhibits in vitro conversion of prion protein into amyloid fibrils.
AB  - In recent studies, the amyloid fibrils produced in vitro from recombinant prion
      protein encompassing residues 89-230 (rPrP 89-230) were shown to produce
      transmissible form of prion disease in transgenic mice (Legname et al., (2004)
      Science 305, 673-676). Long incubation time observed upon inoculation of the
      amyloid fibrils, however, suggests that the fibrils generated in vitro have low
      infectivity titers. These results emphasize the need to define optimal conditions
      for prion conversion in vitro, under which high levels of infectivity can be
      generated in a cell-free system. Because copper(II) has been implicated in normal
      and pathological functions of the prion protein, here we investigated the effect
      of Cu(2+) on cell-free conversion of recombinant PrP. Our results show that at pH
      7.2 and at micromolar concentrations, Cu(2+) inhibited conversion of full-length
      recombinant PrP (rPrP 23-230) into amyloid fibrils. This effect was most
      pronounced for Cu(2+), and less so for Zn(2+), while Mn(2+) had no effect on the
      conversion. Cu(2+)-dependent inhibition of the amyloid formation was less
      effective at pH 6.0, at which rPrP 23-230 displays lower Cu(2+)-binding capacity.
      Using rPrP 89-230, we found that Cu(2+)-dependent inhibition occurred even in the
      absence of octarepeat region; however, it was less effective. Our further studies
      indicated that Cu(2+) inhibited conversion by stabilizing a nonamyloidogenic PK
      resistant form of alpha-rPrP. Remarkably, Cu(2+) also had a profound effect on
      preformed amyloid fibrils. When added to the fibrils, Cu(2+) induced long-range
      coiling of individual fibrils and enhanced their PK-resistance. It, however,
      produced only minor changes in their secondary structures. In addition, Cu(2+)
      induced further aggregation of the amyloid fibrils into large clumps, presumably,
      through interfibrillar coordination of copper ions by octarepeats. Taken
      together, our studies suggest that the role of Cu(2+) in the pathogenesis of
      prion diseases is complex. Because Cu(2+) may inhibit prion replication, while at
      the same time stabilize disease-specific isoform against proteolytic clearance,
      the final outcome of copper-induced effect on progression of prion disease may
      not be straightforward.

PMID- 15865424
TI  - Investigation of ligand binding and protein dynamics in Bacillus subtilis
      chorismate mutase by transverse relaxation optimized spectroscopy-nuclear
      magnetic resonance.
AB  - The structural and dynamical consequences of ligand binding to a monofunctional
      chorismate mutase from Bacillus subtilis have been investigated by solution NMR
      spectroscopy. TROSY methods were employed to assign 98% of the backbone (1)H(N),
      (1)H(alpha), (15)N, (13)C', and (13)C(alpha) resonances as well as 86% of the
      side chain (13)C resonances of the 44 kDa trimeric enzyme at 20 degrees C. This
      information was used to map chemical shift perturbations and changes in
      intramolecular mobility caused by binding of prephenate or a transition state
      analogue to the X-ray structure. Model-free interpretation of backbone dynamics
      for the free enzyme and its complexes based on (15)N relaxation data measured at
      600 and 900 MHz showed significant structural consolidation of the protein in the
      presence of a bound ligand. In agreement with earlier structural and biochemical
      studies, substantial ordering of 10 otherwise highly flexible residues at the C
      terminus is particularly notable. The observed changes suggest direct contact
      between this protein segment and the bound ligand, providing support for the
      proposal that the C-terminus can serve as a lid for the active site, limiting
      diffusion into and out of the pocket and possibly imposing conformational control
      over substrate once bound. Other regions of the protein that experience
      substantial ligand-induced changes also border the active site or lie along the
      subunit interfaces, indicating that the enzyme adapts dynamically to ligands by a
      sort of induced fit mechanism. It is believed that the mutase-catalyzed
      chorismate-to-prephenate rearrangement is partially encounter controlled, and
      backbone motions on the millisecond time scale, as seen here, may contribute to
      the reaction barrier.

PMID- 15865425
TI  - The relationship between aminoglycosides' RNA binding proclivity and their
      antiplasmid effect on an IncB plasmid.
AB  - Bacteria routinely become resistant to antibiotics through the uptake of plasmids
      that encode resistance-mediating proteins. Such plasmid-based resistance is seen
      extensively in clinical settings and has been documented for a wide variety of
      bacterial infections from both Gram-positive and Gram-negative organisms. We
      recently reported that a small molecule could be used to mimic a natural process
      of plasmid elimination, called plasmid incompatibility, and that the addition of
      this compound causes elimination of an IncB plasmid from E. coli and a subsequent
      resensitization to antibiotics [DeNap, Thomas, Musk, and Hergenrother (2004) J.
      Am. Chem. Soc. 126, 15402-15404]. Described herein is a further substantiation
      and validation of the notion that plasmid incompatibility can be mimicked with
      small molecules that bind to important RNA targets controlling plasmid
      replication. In this study, the dissociation constant and stoichiometry of RNA
      binding are determined for 12 aminoglycosides with stem-loop I (SLI) of the IncB
      replication machinery. Importantly, it is found that compounds that do not bind
      to this RNA replication control element fail to induce plasmid loss in vivo,
      whereas those that do bind to the RNA typically cause measurable plasmid loss.
      These results highlight the potential for targeting key RNA regions for induction
      of plasmid loss and the subsequent resensitization of bacteria to antibiotics.

PMID- 15865426
TI  - Aspartate 120 of Escherichia coli methylenetetrahydrofolate reductase: evidence
      for major roles in folate binding and catalysis and a minor role in flavin
      reactivity.
AB  - Escherichia coli methylenetetrahydrofolate reductase (MTHFR) catalyzes the NADH
      linked reduction of 5,10-methylenetetrahydrofolate (CH(2)-H(4)folate) to 5
      methyltetrahydrofolate (CH(3)-H(4)folate) using flavin adenine dinucleotide (FAD)
      as cofactor. MTHFR is unusual among flavin oxidoreductases because it contains a
      conserved, negatively rather than positively charged amino acid (aspartate 120)
      near the N1-C2=O position of the flavin. At this location, Asp 120 is expected to
      influence the redox properties of the enzyme-bound FAD. Modeling of the CH(3)
      H(4)folate product into the enzyme active site suggests that Asp 120 may also
      play crucial roles in folate binding and catalysis. We have replaced Asp 120 with
      Asn, Ser, Ala, Val, and Lys and have characterized the mutant enzymes. Consistent
      with a loss of negative charge near the flavin, the midpoint potentials of the
      mutants increased from 17 to 30 mV. A small kinetic effect on the NADH reductive
      half-reaction was also observed as the mutants exhibited a 1.2-1.5-fold faster
      reduction rate than the wild-type enzyme. Catalytic efficiency (k(cat)/K(m)) in
      the CH(2)-H(4)folate oxidative half-reaction was decreased significantly (up to
      70000-fold) and in a manner generally consistent with the negative charge density
      of position 120, supporting a major role for Asp 120 in electrostatic
      stabilization of the putative 5-iminium cation intermediate during catalysis. Asp
      120 is also intimately involved in folate binding as increases in the apparent
      K(d) of up to 15-fold were obtained for the mutants. Examining the E(red) + CH(2)
      H(4)folate reaction at 4 degrees C, we obtained, for the first time, evidence for
      the rapid formation of a reduced enzyme-folate complex with wild-type MTHFR. The
      more active Asp120Ala mutant, but not the severely impaired Asp120Lys mutant,
      demonstrated the species, suggesting a connection between the extent of complex
      formation and catalytic efficiency.

PMID- 15865427
TI  - Role of the intramolecular hydrogen bond network in the inhibitory power of
      chymotrypsin inhibitor 2.
AB  - A series of mutants of chymotrypsin inhibitor 2 (CI2), at residues involved in
      intramolecular interactions that shape and constrain the binding loop, were
      studied to determine their relative importance for inhibition of the serine
      protease subtilisin BPN', and for resistance of the inhibitor to proteolysis.
      These functional properties were investigated in tandem with the crystal
      structures of the mutant inhibitor-enzyme complexes. A dense hydrogen bonding
      network that supports the binding loop in the vicinity of the scissile bond was
      found to be important both for enzyme affinity and for stability to proteolysis.
      Structural analysis, in combination with biochemical measurements, allows
      differentiation of the structural components most important for resistance to
      proteolysis and/or binding. The most critical participating residues in the
      network were found to be Thr-58, Glu-60, Arg-65, and Gly-83. Glu-60 is more
      important for resistance to proteolysis than for binding, while Arg-65 and two
      other Arg residues play a greater role in binding than in resistance to
      proteolysis. Structural comparisons reveal a wide variety of subtle
      conformational changes in response to mutation, with built-in robustness in the
      hydrogen bond network, such that loss of one contact is compensated by other new
      contacts.

PMID- 15865428
TI  - Formation and reorientation of glucose 1,6-bisphosphate in the PMM/PGM reaction:
      transient-state kinetic studies.
AB  - The interconversion of glucose 1-phosphate and glucose 6-phosphate, catalyzed by
      Pseudomonas aeruginosa phosphomannomutase/phosphoglucomutase, has been studied by
      transient-state kinetic techniques. Glucose 1,6-bisphosphate is formed as an
      intermediate in the reaction, but an obligatory step in the catalytic cycle
      appears to be the formation of an enzyme-glucose 1,6-bisphosphate complex that is
      not competent to form either glucose 1-phosphate or glucose 6-phosphate directly.
      We suggest that during the lifetime of this complex the glucose 1,6-bisphosphate
      intermediate undergoes the 180 degrees reorientation that is required for
      completion of the catalytic cycle. The formation of glucose 1,6-bisphosphate from
      glucose 1-phosphate is in rapid equilibrium relative to the rest of the reaction,
      where K(eq) = 0.14. In the opposite direction, glucose 1,6-bisphosphate is formed
      from glucose 6-phosphate with a rate constant of 12 s(-)(1), and the reverse step
      occurs with a rate constant of 255 s(-)(1). The interconversion of the productive
      and nonproductive glucose 1,6-bisphosphate complexes occurs with a rate constant
      of 64 s(-)(1) in one direction and 48 s(-)(1) in the other direction. Glucose 1,6
      bisphosphate remains associated with the enzyme during reorientation. Isotope
      trapping studies indicate that it partitions to form glucose 1-phosphate or
      glucose 6-phosphate 14.3 times more frequently than it dissociates from the
      enzyme.

PMID- 15865429
TI  - Natural mutations in a 2'-5' oligoadenylate synthetase transgene revealed
      residues essential for enzyme activity.
AB  - Unlike other RNA polymerases, 2'-5' oligoadenylate synthetases, a family of
      interferon-induced enzymes, catalyze the formation of 2'-5', not 3'-5',
      phosphodiester bonds. Moreover, to be active, these proteins require double
      stranded RNA as a cofactor. We have been identifying the specific residues of
      these proteins that impart their novel properties. Here, we report the identity
      of three such residues that underwent natural mutations in a transgenic mouse
      line. When deliberately introduced into recombinant proteins, each of these
      mutations rendered the protein enzymatically inactive. In an effort to understand
      the roles of these residues in enzyme activity, new mutants carrying other
      residues in one of these three sites were generated. Detailed characterization of
      the properties of the mutant proteins revealed that Lys 404 is needed for proper
      binding of the acceptor substrate, Pro 500 provides structural flexibility to the
      protein, and Ser 471 is probably required for its proper folding. This study
      illustrates the power of using natural mutations in transgenes as guides for
      studying structure-function relationships of proteins.

PMID- 15865430
TI  - Two photoaffinity analogues of the tripeptide, hemiasterlin, exclusively label
      alpha-tubulin.
AB  - A synthetic analogue of the tripeptide hemiasterlin, designated HTI-286,
      depolymerizes microtubules, is a poor substrate for P-glycoprotein, and inhibits
      the growth of paclitaxel-resistant tumors in xenograft models. Two radiolabeled
      photoaffinity analogues of HTI-286, designated 4-benzoyl-N,beta,beta-trimethyl-l
      phenylalanyl-N(1)-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N(1),3-dimethyl-l
      valinamide (probe 1) and N,beta,beta-trimethyl-l-phenylalanyl-4-benzoyl-N
      [(1S,2E)-3-carboxy-1-isopropyl-2-butenyl]-N,beta,beta-trimethyl-l
      phenylalaninamide (probe 2), were made to help identify HTI-286 binding sites in
      tubulin. HTI-286, probe 1, and probe 2 had similar affinities for purified
      tubulin [apparent K(D(app)) = 0.2-1.1 microM], inhibited polymerization of
      purified tubulin approximately 80%, and were potent inhibitors of cell growth
      (IC(50) = 1.0-22 nM). Both radiolabeled probes labeled exclusively alpha-tubulin.
      Labeling by [(3)H]probe 1 was inhibited by probe 1, HTI-286, vinblastine, or
      dolastatin 10 (another peptide antimitotic agent that depolymerizes microtubules)
      but was either unaffected or enhanced (at certain temperatures) by colchicine or
      paclitaxel. [(3)H]Probe 1 also labeled exclusively tubulin in cytosolic extracts
      of whole cells. The major, if not exclusive, contact site for probe 1 was mapped
      to residues 314-339 of alpha-tubulin and corresponds to the sheet 8 and helix 10
      region. This region is known to (1) have longitudinal interactions with beta
      tubulin across the interdimer interface, (2) have lateral interactions with
      adjacent protofilaments, and (3) contact the N-terminal region of stathmin, a
      protein that induces depolymerization of tubulin. Binding of probe 1 to this
      region may alter the conformation of tubulin outside the labeling domain, since
      enzymatic removal of the C-terminus of only alpha-tubulin by subtilisin after,
      but not before, photolabeling is blocked by probe 1. These results suggest that
      hemiasterlin is in close contact with alpha-tubulin and may span the interdimer
      interface so that it contacts the vinblastine- and dolastatin 10-binding sites
      believed to be in beta-tubulin. In addition, we speculate that antimitotic
      peptides mimic the interaction of stathmin with tubulin.

PMID- 15865431
TI  - First crystal structures of human carbonic anhydrase II in complex with dual
      aromatase-steroid sulfatase inhibitors.
AB  - Carbonic anhydrase (CA) catalyzes the reversible hydration of carbon dioxide to
      hydrogen carbonate. The role of CA in maintaining pH balance has made it an
      attractive drug target for the treatment of cancer, and it has recently been
      implicated in the delivery of sulfamate-containing drugs. With the acceptance of
      steroid sulfatase as a target for hormone-dependent cancer, novel dual aromatase
      steroid sulfatase inhibitors (DASIs) containing a sulfamate group are now being
      developed. In this study, we show that CA II is potently inhibited by several
      members of this class of inhibitor. The structures of CA II complexed with 4-[(4
      O-sulfamoylbenzyl)(4-cyanophenyl)amino]-4H-[1,2,4]triazole (K(D) = 84 +/- 5 nM)
      and 4-[(3-bromo-4-O-sulfamoylbenzyl)(4-cyanophenyl)amino]-4H-[1,2,4]triazole
      (K(D) = 454 +/- 29 nM) are reported to 2.02 and 1.76 A, respectively. Both
      inhibitors ligate to the active site zinc(II) atom via their sulfamate nitrogen,
      while the rest of the molecule is contained within the hydrophobic binding
      pocket. Key protein residues include Val-121, Phe-131, Val-135, Val-143, Leu-141,
      Leu-198, Pro-202, and Leu-204. Despite being structurally similar, the two
      ligands experience different types of binding particularly in the sulfamate
      containing aromatic ring and the opposite geometric arrangement of the triazole
      and cyanophenyl groups around the configurationally invertible central nitrogen
      atom. Small changes in inhibitor structure can cause large changes in binding to
      CA II, and this underlines the importance of structure-based drug design with
      this enzyme and other isoforms relevant to potential anticancer therapy.
      Moreover, these results underpin the idea that binding to erythrocyte CA II may
      be a general method of stabilizing and delivering sulfamate-based drugs in vivo.

PMID- 15865432
TI  - Regulation of myosin-IIA assembly and Mts1 binding by heavy chain
      phosphorylation.
AB  - Previous studies suggested that heavy chain phosphorylation regulates non-muscle
      myosin-II assembly in an isoform-specific manner, affecting the assembly of
      myosin-IIB, but not myosin-IIA. We re-examined the effects of heavy chain
      phosphorylation on myosin-IIA filament formation and also examined mts1 binding.
      We demonstrated that heavy chain phosphorylation by either protein kinase C (PKC)
      or casein kinase 2 (CK2) inhibits the assembly of myosin-IIA into filaments. PKC
      phosphorylation had no affect on mts1 binding, but CK2 phosphorylation decreased
      the affinity of mts1 for the myosin-IIA rod by approximately 6.5-fold. Mts1
      destabilized PKC-phosphorylated myosin-IIA filaments and inhibited the assembly
      of myosin-IIA monomers with maximal inhibition of assembly and promotion of
      disassembly occurring at a molar ratio of one mts1 dimer per myosin-IIA rod. At
      this molar ratio, mts1 only weakly disassembled CK2-phosphorylated myosin-IIA
      filaments and weakly inhibited the assembly of CK2-phosphorylated myosin-IIA
      monomers. These observations demonstrate that CK2 phosphorylation of the myosin
      IIA heavy chain protects against mts1-induced filament disassembly and inhibition
      of assembly, and suggest that heavy chain phosphorylation provides an additional
      level of regulation for the mts1-myosin-IIA interaction.

PMID- 15865433
TI  - Framework model for DNA polymerases.
AB  - DNA polymerases are complex machines with both chemical and mechanical functions.
      Recent crystal structures, ensemble kinetics, and single-molecule investigations
      have helped to elucidate the main properties of several DNA polymerases, all of
      which share common structural elements and a common basic mechanism, despite wide
      variations in amino acid sequence. The framework model is intended to aid in the
      understanding of these common features (and differences). It defines a class of
      models that automatically incorporates most of what is known about DNA
      polymerases within a single theoretical structure so that it is easier to make
      comparisons between them and to generate detailed models for specific
      polymerases. The framework model has three main elements: (1) a set of four key
      variables that describe the important motions within the protein-DNA-nucleotide
      complex, (2) a complete set of conformational states for the protein-DNA
      nucleotide system, and (3) an approximate potential energy surface that controls
      the motions and transition rates between states. As an example application, we
      use the general framework ideas to build a detailed model for the HIV reverse
      transcriptase that is consistent with existing data, and predicts force-velocity
      curves and stepping-statistics histograms that can be directly compared to
      experiment.

PMID- 15865434
TI  - Keap1, the sensor for electrophiles and oxidants that regulates the phase 2
      response, is a zinc metalloprotein.
AB  - Induction of the phase 2 response, a major cellular reaction to
      oxidative/electrophile stress depends on a protein triad: actin-tethered Keap1
      that binds to Nrf2. Inducers react with Keap1 releasing Nrf2 for nuclear
      translocation and activation of the antioxidant response element (ARE), which
      regulates phase 2 genes. The primary sensors for inducers are certain uniquely
      reactive cysteine thiols of Keap1. Recombinant murine Keap1 contains 0.9 zinc
      atoms per monomer as determined by inductively coupled plasma-optical emission
      spectrometry: its zinc content depends on the metal composition of the
      overexpression medium. Simultaneous direct measurement of bound zinc using a
      pyridazoresorcinol chelator and protein thiol groups using 4,4'-dipyridyl
      disulfide has established that (i) zinc is bound to reactive cysteine thiols of
      Keap1 and is displaced stoichiometrically by inducers, (ii) with these cysteines
      mutated to alanine, the affinity for zinc is reduced by nearly 2 orders of
      magnitude, and (iii) the association constant of Keap1 for zinc is 1.02 (+/-0.19)
      x 10(11) M(-)(1), consistent with a Zn(2+) metalloprotein. Co(2+) substitution
      for Zn(2+) yields an optical spectrum consistent with tetrahedral metal
      coordination. Coincident binding of inducers and release of zinc alters the
      conformation of Keap1, as shown by a profound decline of its tryptophan
      fluorescence and depression of fluorescence of a hydrophobicity probe. Thus,
      regulation of the phase 2 response involves chemical modification of critical
      cysteine residues of Keap1, whose reactivity is modulated by zinc binding. Keap1
      is a zinc-thiol protein endowed with a delicate switch controlled by both metal
      binding and thiol reactivity.

PMID- 15865435
TI  - Estrogen-induced mitochondrial reactive oxygen species as signal-transducing
      messengers.
AB  - We report here evidence in support of the role of 17beta-estradiol- (E2-) induced
      mitochondrial (mt) reactive oxygen species (ROS) as signal-transducing
      messengers. On the basis of monitoring the oxidation of 2',7'-dichlorofluorescin
      by spectrofluorometry, flow cytometry, and confocal microscopy, we have
      identified that exposure of E2 triggers the immediate rapid production of
      intracellular ROS ranging from a 1- to severalfold increase in a variety of
      cells. E2-stimulated ROS production does not correlate with the activity of the
      estrogen receptor (ER) in the cells. The ROS is most likely hydrogen peroxide
      based on its inhibition by antioxidants and catalase and lack of any effects of
      E2 on O(2)(*)(-) or NO(*) formation. Confocal microscopy showed that ROS is
      localized in the perinuclear mitochondria. E2 through anchorage- and integrin
      dependent signaling to mitochondria increased ROS generation. Increased
      intracellular ROS formation identified here for the first time may explain the
      mechanism of previously reported oxidative damage and subsequent genetic
      alterations including mutations produced by elevated concentrations of estrogens.
      The functional consequences of E2-induced ROS formation included the enhanced
      cell motility as shown by the increase in cdc42 and activation of Pyk2 and the
      increased phosphorylation of signaling proteins c-jun and CREB. E2-induced ROS
      activated the binding of three oxidant-sensitive transcription factors: AP-1,
      CREB, and nuclear respiratory factor 1. In addition to ERs as signaling
      molecules, our findings further revealed that E2-induced mt ROS also act as
      signal transducing messengers and suggest new targets for the development of
      antioxidant-based drugs or antioxidant gene therapy for the prevention and
      treatment of estrogen-dependent cancer.

PMID- 15865436
TI  - Green fluorescent protein-expressing Escherichia coli as a selective probe for
      HOCl generation within neutrophils.
AB  - Escherichia coli were transformed by electroporation to introduce a plasmid
      harboring a GFP gene-containing vector. The fluorescence of the purified GFP
      isolated from the transformant was quenched by myeloperoxidase (MPO)-generated
      HOCl, by peroxynitrous acid (ONOOH) and by enzymatically or radiolytically
      generated NO(2)(.) but not by other putative neutrophil-generated oxidants.
      Fluorescence from the bacterium was effectively quenched by HOCl but not
      peroxynitrite, oxidizing radicals derived from its O-O bond homolysis, or the
      other oxidants under study. Exposure of serum-opsonized bacteria to human
      neutrophils resulted in extensive loss of GFP fluorescence; fluorescence
      microscopy revealed that phagocytosed bacteria were completely quenched but that
      bacteria remaining in the external media were unquenched. Addition of sodium
      azide to the medium to inhibit MPO prevented neutrophil-mediated fluorescence
      quenching. Because the amount of HOCl required to inhibit bacterial fluorescence
      was an order of magnitude greater than required to inhibit colonial growth, these
      results imply that sufficient HOCl was formed within the neutrophil phagosome to
      kill the microbe.

PMID- 15865437
TI  - Quinone (QB) reduction by B-branch electron transfer in mutant bacterial reaction
      centers from Rhodobacter sphaeroides: quantum efficiency and X-ray structure.
AB  - The photosynthetic reaction center (RC) from purple bacteria converts light into
      chemical energy. Although the RC shows two nearly structurally symmetric
      branches, A and B, light-induced electron transfer in the native RC occurs almost
      exclusively along the A-branch to a primary quinone electron acceptor Q(A).
      Subsequent electron and proton transfer to a mobile quinone molecule Q(B)
      converts it to a quinol, Q(B)H(2). We report the construction and
      characterization of a series of mutants in Rhodobacter sphaeroides designed to
      reduce Q(B) via the B-branch. The quantum efficiency to Q(B) via the B-branch
      Phi(B) ranged from 0.4% in an RC containing the single mutation Ala-M260 --> Trp
      to 5% in a quintuple mutant which includes in addition three mutations to inhibit
      transfer along the A-branch (Gly-M203 --> Asp, Tyr-M210 --> Phe, Leu-M214 -->
      His) and one to promote transfer along the B-branch (Phe-L181 --> Tyr). Comparing
      the value of 0.4% for Phi(B) obtained in the AW(M260) mutant, which lacks Q(A),
      to the 100% quantum efficiency for Phi(A) along the A-branch in the native RC, we
      obtain a ratio for A-branch to B-branch electron transfer of 250:1. We determined
      the structure of the most effective (quintuple) mutant RC at 2.25 A (R-factor =
      19.6%). The Q(A) site did not contain a quinone but was occupied by the side
      chain of Trp-M260 and a Cl(-). In this structure a nonfunctional quinone was
      found to occupy a new site near M258 and M268. The implications of this work to
      trap intermediate states are discussed.

PMID- 15865438
TI  - Role of Lys-226 in the catalytic mechanism of Bacillus stearothermophilus serine
      hydroxymethyltransferase--crystal structure and kinetic studies.
AB  - Serine hydroxymethyltransferase (SHMT), a pyridoxal 5'-phosphate (PLP)-dependent
      enzyme catalyzes the reversible conversion of l-Ser and
      tetrahydropteroylglutamate (H(4)PteGlu) to Gly and 5,10-methylene
      tetrahydropteroylglutamate (CH(2)-H(4)PteGlu). Biochemical and structural studies
      on this enzyme have implicated several residues in the catalytic mechanism, one
      of them being the active site lysine, which anchors PLP. It has been proposed
      that this residue is crucial for product expulsion. However, in other PLP
      dependent enzymes, the corresponding residue has been implicated in the proton
      abstraction step of catalysis. In the present investigation, Lys-226 of Bacillus
      stearothermophilus SHMT (bsSHMT) was mutated to Met and Gln to evaluate the role
      of this residue in catalysis. The mutant enzymes contained 1 mol of PLP per mol
      of subunit suggesting that Schiff base formation with lysine is not essential for
      PLP binding. The 3D structure of the mutant enzymes revealed that PLP was bound
      at the active site in an orientation different from that of the wild-type enzyme.
      In the presence of substrate, the PLP ring was in an orientation superimposable
      with that of the external aldimine complex of wild-type enzyme. However, the
      mutant enzymes were inactive, and the kinetic analysis of the different steps of
      catalysis revealed that there was a drastic reduction in the rate of formation of
      the quinonoid intermediate. Analysis of these results along with the crystal
      structures suggested that K-226 is responsible for flipping of PLP from one
      orientation to another which is crucial for H(4)PteGlu-dependent Calpha-Cbeta
      bond cleavage of l-Ser.

PMID- 15865439
TI  - Novel cytosolic binding partners of the neural cell adhesion molecule: mapping
      the binding domains of PLC gamma, LANP, TOAD-64, syndapin, PP1, and PP2A.
AB  - The neural cell adhesion molecule (NCAM) is implicated in important functions
      during development and maintenance of the nervous system. Two of the three major
      isoforms, NCAM 140 and NCAM 180, are transmembrane glycoproteins with large
      cytoplasmic domains of different length. The purpose of this study was to
      identify novel intracellular binding partners of NCAM 140 and NCAM 180. We
      expressed both cytoplasmic domains, as well as cytoplasmic fragments of NCAM, as
      fusion proteins in Escherichia coli and used them for ligand affinity
      chromatography or glutathione S-transferase (GST) pull-down assays. By peptide
      mass fingerprinting Western blot analysis, or both, we identified PLCgamma, LANP,
      syndapin, PP1, and PP2A as binding partners for both NCAM 140 and NCAM 180,
      whereas TOAD-64 was identified as a NCAM 180-specific interacting protein.
      Furthermore, we were able to show that binding of these novel binding proteins,
      as well as the previously described interaction partners ROK alpha (rho A binding
      kinase alpha) and alpha- and beta-tubulin, bind to specific cytosolic sequences
      of NCAM. For this purpose, we performed GST pull-down experiments using cytosolic
      fragments of NCAM as GST-fusion proteins and cytosolic- or cytoskeleton-enriched
      protein fractions of rat brain.

PMID- 15865440
TI  - Crystal structure of murine 11 beta-hydroxysteroid dehydrogenase 1: an important
      therapeutic target for diabetes.
AB  - 11Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the conversion
      of 11-dehydrocorticosterone to its active form corticosterone in rodents (or
      cortisone to cortisol in humans). The reductive reaction of the 11-keto to 11
      hydroxyl is the pivotal switch in the activation of glucocorticoids. An excess of
      active glucocorticoids has been shown to play a key role in metabolic disorders
      such as diabetes and obesity. Therefore, 11beta-HSD1 represents an important
      therapeutic target for the treatment of these diseases. To facilitate the
      iterative design of inhibitors, we have crystallized and determined the three
      dimensional structures of a binary complex of murine 11beta-HSD1 with NADP(H) to
      a resolution of 2.3 A and of a ternary complex with corticosterone and NADP(H) to
      a resolution of 3.0 A by X-ray crystallography. The enzyme forms a homodimer in
      the crystal and has a fold similar to those of other members of the family of
      short chain steroid dehydrogenases/reductases (SDRs). The structure shows a novel
      folding feature at the C-terminus of the enzyme. The C-terminal helix insertions
      provide additional dimer contacts, exert an influence on the conformations of the
      substrate binding loops, and present hydrophobic regions for potential membrane
      attachment. The structure also reveals how 11beta-HSD1 achieves its selectivity
      for its substrate.

PMID- 15865441
TI  - The role of G beta gamma and domain interfaces in the activation of G protein
      coupled receptor kinase 2.
AB  - In response to extracellular signals, G protein-coupled receptors (GPCRs)
      catalyze guanine nucleotide exchange on Galpha subunits, enabling both activated
      Galpha and Gbetagamma subunits to target downstream effector enzymes. One target
      of Gbetagamma is G protein-coupled receptor kinase 2 (GRK2), an enzyme that
      initiates homologous desensitization by phosphorylating activated GPCRs. GRK2
      consists of three distinct domains: an RGS homology (RH) domain, a protein kinase
      domain, and a pleckstrin homology (PH) domain, through which it binds Gbetagamma.
      The crystal structure of the GRK2-Gbetagamma complex revealed that the domains of
      GRK2 are intimately associated and left open the possibility for allosteric
      regulation by Gbetagamma. In this paper, we report the 4.5 A structure of GRK2,
      which shows that the binding of Gbetagamma does not induce large domain
      rearrangements in GRK2, although small rotations of the RH and PH domains
      relative to the kinase domain are evident. Mutation of residues within the larger
      domain interfaces of GRK2 generally leads to diminished expression and activity,
      suggesting that these interfaces are important for stability and remain intact
      upon activation of GRK2. Geranylgeranylated Gbetagamma, but not a soluble mutant
      of Gbetagamma, protects GRK2 from clostripain digestion at a site within its
      kinase domain that is 80 A away from the Gbetagamma binding site. Equilibrium
      ultracentrifugation experiments indicate that neither abnormally large detergent
      micelles nor protein oligomerization can account for the observed protection. The
      Gbetagamma-mediated binding of GRK2 to CHAPS micelles or lipid bilayers therefore
      appears to rigidify the kinase domain, perhaps by encouraging stable contacts
      between the RH and kinase domains.

PMID- 15865442
TI  - Molecular mechanism of the intracellular segments of the melanocortin-4 receptor
      for NDP-MSH signaling.
AB  - Mutations of the human melanocortin-4 receptor (hMC4R) have been previously
      identified to be the most common cause of monogenic human obesity. Specifically,
      mutations of the intracellular C terminus and the third intracellular loop of
      hMC4R have been reported to play an important role in human obesity. However, the
      molecular basis of these hMC4R intracellular segments in receptor function
      remains unclear. In this study, we utilized deletions and mutations of specific
      portions of the hMC4R to determine the molecular mechanism of both the C terminus
      and the third intracellular loop in receptor signaling. Our results indicate that
      deletions of the distal 25 (the entire C terminus), 22, 18, 17, 16, and 15 amino
      acids of the C terminus result in the complete loss of both [Nle(4)-d-Phe(7)]
      alpha-melanocyte stimulating hormone (NDP-MSH) binding and NDP-MSH-mediated cAMP
      production. Deletion of the distal 14 amino acids of the C terminus significantly
      decreases both NDP-MSH binding affinity and potency, but deletion of the distal
      13 amino acids of the C terminus does not affect NDP-MSH activity. Further
      analysis revealed that the proximal 12 amino acids of the C terminus are not only
      important for receptor signaling but also important for ligand binding. Our
      results also indicate that the third intracellular loop of the hMC4R is important
      for receptor signaling but not ligand binding. In summary, our findings suggest
      that the proximal region of the melanocortin-4 receptor (MC4R) C terminus is
      crucial not only for receptor signaling but also for ligand binding, while the
      third intracellular loop is important mainly for receptor signaling.

PMID- 15865443
TI  - Hierarchical phosphorylation of the TNF-alpha receptor, TNF-R1, by p42Mapk/Erk at
      basic Pro-directed kinase sites.
AB  - Phosphorylation of the TNF-alpha receptor TNF-R1 has been shown to differentially
      regulate receptor signaling and function and promote changes in its subcellular
      localization. Previous studies have shown that p42(mapk/erk2) phosphorylates Ser
      and Thr residues (T236, S240, S244, and S270) in the membrane proximal region of
      TNF-R1 and that mutation of these residues to Glu and Asp residues (TNF-R1.4D/E)
      mimics the effect of phosphorylation on receptor signaling and localization. In
      the present study, we investigated whether the initial phosphorylation of these
      residues by p42(mapk/erk2) promotes hierarchical phosphorylation of additional
      sites within the cytoplasmic domain of TNF-R1. This question was addressed by
      investigating the ability of the TNF-R1.4D/E mutant receptor to be phosphorylated
      in in vitro kinase assays using GST-mutant cytoplasmic domain fusion proteins as
      substrates and in intact cells following mutant receptor expression. In addition,
      we determined the location of the additional phosphorylation sites. Incubation of
      Sepharose bead-bound GST-TNF-R1(207)(-)(425).4D/E fusion protein with lysates
      containing activated p42(mapk/erk2) led to the phosphorylation of Ser and Thr
      residues in addition to the previously defined sites at T236, S240, S244, and
      S270. Deletional mutagenesis localized these residues to a stretch of 14 amino
      acids that encompasses three basic Pro-directed ([S/T]P) kinase consensus
      sequences located between residues S256 and T267. Point mutagenesis of T257,
      S262, and T267 to Ala residues indicated that these sites are targets of
      phosphorylation by p42(mapk/)(erk2). These findings support the conclusion that
      p42(mapk/erk2) promotes extensive phosphorylation of the membrane proximal region
      in a hierarchical fashion at both consensus and nonconsensus ERK-phosphorylation
      sites.

PMID- 15865444
TI  - Comprehensive identification of post-translational modifications of rat bone
      osteopontin by mass spectrometry.
AB  - Osteopontin (OPN) is a highly modified protein that is found in many tissues and
      has been associated with a variety of physiological and pathological processes.
      Bone OPN is a potent inhibitor of hydroxyapatite crystal formation and stimulates
      bone resorption by osteoclasts; these activities, as well as others, are
      dependent upon phosphorylation of the protein. We have used mass spectrometry
      (MS) to perform a comprehensive analysis of the post-translational modification
      of OPN purified from rat bone. Matrix-assisted laser desorption time-of-flight
      (MALDI-TOF) MS showed masses of 37.6 and 36.8 kDa before and after enzymatic
      dephosphorylation, respectively, corresponding to a content of approximately 10.4
      phosphate groups. Using proteolytic digestion and tandem MS, we localized 29
      sites of phosphorylation: S10, S11, S46, S47, T50, S60, S62, S65, S146, T154,
      S160, S164, S167, S193, S196, S203, S220, S223, S232, S241, S245, S257, S262,
      S267, S278, S290, S295, S296, and S297. In addition, Y150 was shown to be
      sulfated and T107, T110, T116, and T121 are O-glycosylated. No glycan was
      detected at the potential N-glycosylation site. Other modifications, including
      deamidation, oxidation, and carbamylation, are also present. A 36-amino acid
      sequence from residues 67-102 could not be analyzed in detail, even after
      sialidase treatment, presumably because of the presence of a large number of
      acidic residues. In comparison to the previously characterized cow milk isoform,
      rat bone OPN is sulfated and has an additional site of glycosylation, many
      different sites of phosphorylation, and a lower overall phosphate content.

PMID- 15865445
TI  - Point mutations at the type I Cu ligands, Cys457 and Met467, and at the putative
      proton donor, Asp105, in Myrothecium verrucaria bilirubin oxidase and reactions
      with dioxygen.
AB  - The type I Cu site in the Cys457Ser mutant of Myrothecium verrucaria bilirubin
      oxidase was vacant, but the trinuclear center composed of a type II Cu and a pair
      of type III Cu's was fully occupied by three Cu ions. Cys457Ser could react with
      dioxygen, affording reaction intermediate I with absorption maxima at 340, 470,
      and 675 nm. This intermediate corresponds to that obtained from laccase, whose
      type I Cu is cupric and type II and III Cu's are cuprous [Zoppellaro, G.,
      Sakurai, T., and Huang, H. (2001) J. Biochem. 129, 949-953] or whose type I Cu is
      substituted with Hg [Palmer, A. E., Lee, S. K., and Solomon, E. I. (2001) J. Am.
      Chem. Soc. 123, 6591-6599]. Another type I Cu mutant, Met467Gln, with modified
      spectroscopic properties and redox potential, afforded reaction intermediate II
      with absorption maxima at 355 and 450 nm. This intermediate corresponds to that
      obtained during the reaction of laccase [Sundaram, U. M., Zhang, H. H., Hedman,
      B., Hodgson, K. O., and Solomon, E. I. (1997) J. Am. Chem. Soc. 119, 12525-12540;
      Huang, H., Zoppellaro, G., and Sakurai, T. (1999) J. Biol. Chem. 274, 32718
      32724]. According to a three-dimensional model of bilirubin oxidase, Asp105 is
      positioned near the trinuclear center. Asp105Glu and Asp105Ala exhibited 46 and
      7.5% bilirubin oxidase activity compared to the wild-type enzyme, respectively,
      indicating that Asp105 conserved in all multi-copper oxidases donates a proton to
      reaction intermediates I and II. In addition, this amino acid might be involved
      in the formation of the trinuclear center and in the binding of dioxygen based on
      the difficulties in incorporating four Cu ions in Asp105Ala and Asp105Asn and
      their reactions with dioxygen.

PMID- 15865446
TI  - Cooperative sub-millisecond folding kinetics of apomyoglobin pH 4 intermediate.
AB  - For small single-domain proteins, formation of the native conformation (N) from a
      fully unfolded form (U) or from a partially folded intermediate (I) occurs
      typically in a highly cooperative process that can be described by a two-state
      model. However, it is not clear whether cooperativity arises early along the
      folding reaction and whether folding intermediates are also formed in highly
      cooperative processes. Here, we show that each previously identified step leading
      apomyoglobin from its unfolded form to its native form, namely, the U <= => Ia,
      the Ia <= => Ib, and the Ib <= => N reactions, exhibits typical features of a two
      state reaction. First, refolding and unfolding kinetics of the earliest U <= =>
      Ia reaction are measurable at pH 4.2 within the urea-induced unfolding transition
      [Jamin, M., and Baldwin, R. L. (1996) Nat. Struct. Biol. 3, 613-618; Jamin, M.,
      and Baldwin, R. L. (1998) J. Mol. Biol. 276, 491-504], and we report here that
      sub-millisecond kinetics measured by far-UV circular dichroism (CD), a probe of
      secondary structure, are similar to those measured by Trp fluorescence, a probe
      of hydrophobic core formation and chain collapse. These results confirm that
      folding of the earliest intermediate, Ia, occurs in a highly cooperative process,
      in which hydrophobic collapse and secondary structure formation occur
      concomitantly in the A(B)GH core. Second, when the refolding of N is measured at
      high pH, starting from the acid-unfolded ensemble, the formation of Ia occurs in
      the mixing time of the sub-millisecond stopped-flow, but the subsequent steps,
      the Ia <= => Ib and Ib <= => N reactions, exhibit similar kinetics by far-UV CD
      and Trp fluorescence, indicating that these two late stages of the apoMb folding
      process also occur in highly cooperative, two-state reactions.

PMID- 15865447
TI  - Sulfur dehydrogenase of Paracoccus pantotrophus: the heme-2 domain of the
      molybdoprotein cytochrome c complex is dispensable for catalytic activity.
AB  - Sulfur dehydrogenase, Sox(CD)(2), is an essential part of the sulfur-oxidizing
      enzyme system of the chemotrophic bacterium Paracoccus pantotrophus. Sox(CD)(2)
      is a alpha(2)beta(2) complex composed of the molybdoprotein SoxC (43 442 Da) and
      the hybrid diheme c-type cytochrome SoxD (37 637 Da). Sox(CD)(2) catalyzes the
      oxidation of protein-bound sulfur to sulfate with a unique six-electron transfer.
      Amino acid sequence analysis identified the heme-1 domain of SoxD proteins to be
      specific for sulfur dehydrogenases and to contain a novel ProCysMetXaaAspCys
      motif, while the heme-2 domain is related to various cytochromes c(2).
      Purification of sulfur dehydrogenase without protease inhibitor yielded a dimeric
      SoxCD(1) complex consisting of SoxC and SoxD(1) of 30 kDa, which contained only
      the heme-1 domain. The heme-2 domain was isolated as a new cytochrome SoxD(2) of
      about 13 kDa. Both hemes of SoxD in Sox(CD)(2) are redox-active with midpoint
      potentials at E(m)1 = 218 +/- 10 mV and E(m)2 = 268 +/- 10 mV, while SoxCD(1) and
      SoxD(2) both exhibit a midpoint potential of E(m) = 278 +/- 10 mV.
      Electrochemically induced FTIR difference spectra of Sox(CD)(2), SoxCD(1), and
      SoxD(2) were distinct. A carboxy group is protonated upon reduction of the
      SoxD(1) heme but not for SoxD(2). The specific activity of SoxCD(1) and
      Sox(CD)(2) was identical as was the yield of electrons with thiosulfate in the
      reconstituted Sox enzyme system. To examine the physiological significance of the
      heme-2 domain, a mutant was constructed that was deleted for the heme-2 domain,
      which produced SoxCD(1) and transferred electrons from thiosulfate to oxygen.
      These data demonstrated the crucial role of the heme-1 domain of SoxD for
      catalytic activity, electron yield, and transfer of the electrons to the
      cytoplasmic membrane, while the heme-2 domain mediated the alpha(2)beta(2)
      tetrameric structure of sulfur dehydrogenase.

PMID- 15865448
TI  - Biochemical properties of purified human retinol dehydrogenase 12 (RDH12):
      catalytic efficiency toward retinoids and C9 aldehydes and effects of cellular
      retinol-binding protein type I (CRBPI) and cellular retinaldehyde-binding protein
      (CRALBP) on the oxidation and reduction of retinoids.
AB  - Retinol dehydrogenase 12 (RDH12) is a novel member of the short-chain
      dehydrogenase/reductase superfamily of proteins that was recently linked to
      Leber's congenital amaurosis 3 (LCA). We report the first biochemical
      characterization of purified human RDH12 and analysis of its expression in human
      tissues. RDH12 exhibits approximately 2000-fold lower K(m) values for NADP(+) and
      NADPH than for NAD(+) and NADH and recognizes both retinoids and lipid
      peroxidation products (C(9) aldehydes) as substrates. The k(cat) values of RDH12
      for retinaldehydes and C(9) aldehydes are similar, but the K(m) values are, in
      general, lower for retinoids. The enzyme exhibits the highest catalytic
      efficiency for all-trans-retinal (k(cat)/K(m) approximately 900 min(-)(1) microM(
      )(1)), followed by 11-cis-retinal (450 min(-)(1) mM(-)(1)) and 9-cis-retinal (100
      min(-)(1) mM(-)(1)). Analysis of RDH12 activity toward retinoids in the presence
      of cellular retinol-binding protein (CRBP) type I or cellular retinaldehyde
      binding protein (CRALBP) suggests that RDH12 utilizes the unbound forms of all
      trans- and 11-cis-retinoids. As a result, the widely expressed CRBPI, which binds
      all-trans-retinol with much higher affinity than all-trans-retinaldehyde,
      restricts the oxidation of all-trans-retinol by RDH12, but has little effect on
      the reduction of all-trans-retinaldehyde, and CRALBP inhibits the reduction of 11
      cis-retinal stronger than the oxidation of 11-cis-retinol, in accord with its
      higher affinity for 11-cis-retinal. Together, the tissue distribution of RDH12
      and its catalytic properties suggest that, in most tissues, RDH12 primarily
      contributes to the reduction of all-trans-retinaldehyde; however, at saturating
      concentrations of peroxidic aldehydes in the cells undergoing oxidative stress,
      for example, photoreceptors, RDH12 might also play a role in detoxification of
      lipid peroxidation products.

PMID- 15865449
TI  - Roles of the disulfide bond and adjacent residues in determining the reduction
      potentials and stabilities of respiratory-type Rieske clusters.
AB  - Rieske [2Fe-2S] clusters have reduction potentials which vary by over 500 mV, and
      which are pH dependent. In the cytochrome bc(1) complex, the high-potential and
      low-pK values of the cluster may be important in the mechanism of quinol
      oxidation. Hydrogen bonds, from both side-chain and mainchain groups, are crucial
      for these properties, but solvent accessibility and a disulfide bond (present in
      only high-potential Rieske proteins) have been suggested to be important
      determinants also. Previous studies have addressed the hydrogen bonds, disulfide
      bond, and a leucine residue which may restrict solvent access, by mutations in
      the cytochrome bc(1) complex. However, influences on the complex (disruption of
      quinol binding and displacement of the Rieske domain) are difficult to
      deconvolute from intrinsic effects on the Rieske cluster. Here, the effects of
      similar mutations on cluster potential, pK values, and stability are
      characterized comprehensively in the isolated Rieske domain of the bovine
      protein. Hydrogen bonds from Ser163 and Tyr165 are important in increasing the
      reduction potential and decreasing the pK values. The disulfide has a limited
      effect on the redox properties, but is crucial for cluster stability,
      particularly in the oxidized state. Mutations of Leu142 had little effect on
      cluster potential, pK values, or stability, in contrast to the significant
      effects which were observed in the complex. The sum of the effects of all the
      mutated residues accounts for most of the differences between high- and low
      potential Rieske proteins.

PMID- 15865450
TI  - Loss of DNA minor groove interactions by exonuclease-deficient Klenow polymerase
      inhibits O6-methylguanine and abasic site translesion synthesis.
AB  - The importance of DNA polymerase-DNA minor groove interactions on translesion
      synthesis (TLS) was examined in vitro using variants of exonuclease-deficient
      Klenow polymerase and site-specifically modified DNA oligonucleotides. Polymerase
      variant R668A lacks primer strand interactions, while variant Q849A lacks
      template strand interactions. O(6)-Methylguanine (m6G) and abasic site TLS was
      examined in three stages: dNTP insertion opposite the lesion, extension from a
      terminal lesion-containing base pair, and the dissociation equilibrium of the
      polymerase from the lesion-containing template. Less than 5% TLS was observed at
      the insertion step for either variant on the lesion-containing templates. While
      extensive TLS was observed for WT polymerase on the m6G template, only
      incorporation opposite the lesion was observed for the R668A variant. Loss of the
      template strand interaction, Q849A, resulted in the inability to insert dNTPs
      opposite either the m6G or abasic lesion. For both variants, extension of purine
      containing m6G primer-templates was increased relative to WT polymerase. We
      observed similar extension efficiencies for all variants, relative to WT, using
      abasic template-primers. Polymerase dissociation/reassociation was studied
      through the use of a competitor primer/template complex. Dissociation for WT
      polymerase increased 2-fold and 3-fold, respectively, for m6G and abasic lesion
      containing templates, relative to the natural template. Variants lacking DNA
      minor groove interactions displayed increased dissociation from DNA templates,
      relative to WT polymerase, but do not display an increased level of lesion
      induced polymerase dissociation. Our results indicate that the primer and
      template strand interactions of the Klenow polymerase with the DNA minor groove
      are critical for maintaining the DNA-polymerase complex during translesion
      synthesis.

PMID- 15865451
TI  - Characterization of a transient covalent adduct formed during dimethylarginine
      dimethylaminohydrolase catalysis.
AB  - Dimethylarginine dimethylaminohydrolase (DDAH) regulates the concentrations of
      human endogenous inhibitors of nitric oxide synthase, N(omega)-methyl-l-arginine
      (NMMA), and asymmetric N(omega),N(omega)-dimethyl-l-arginine (ADMA).
      Pharmacological regulation of nitric oxide synthesis is an important goal, but
      the catalytic mechanism of DDAH remains largely unexplored. A DDAH from
      Pseudomonas aeruginosa was cloned, and asymmetrically methylated arginine
      analogues were shown to be the preferred substrates, with ADMA displaying a
      slightly higher k(cat)/K(M) value than NMMA. DDAH is similar to members of a
      larger superfamily of guanidino-modifying enzymes, some of which have been shown
      to use an S-alkylthiouronium intermediate during catalysis. No covalent
      intermediates were found to accumulate during steady-state turnover reactions of
      DDAH with NMMA or ADMA. However, identification of a new substrate with an
      activated leaving group, S-methyl-l-thiocitrulline (SMTC), enabled acid trapping
      and ESI-MS characterization of a transient covalent adduct with a mass of 158 +/-
      10 Da that accumulates during steady-state turnover. Subsequent trapping,
      proteolysis, peptide mapping and fragmentation by mass spectrometry, and site
      directed mutagenesis demonstrated that this covalent adduct was attached to an
      active site residue and implicates Cys249 as the catalytic nucleophile required
      for intermediate formation. The use of covalent catalysis clearly links DDAH to
      this superfamily of enzymes and suggests that an S-alkylthiouronium intermediate
      may be a conserved feature in their mechanisms.

PMID- 15865452
TI  - Mechanistic studies of mouse polyamine oxidase with N1,N12-bisethylspermine as a
      substrate.
AB  - In mammalian cells, the flavoprotein polyamine oxidase catalyzes a key step in
      the catabolism of polyamines, the oxidation of N1-acetylspermine and N1
      acetylspermidine to spermidine and putrescine, respectively. The mechanism of the
      mouse enzyme has been studied with N1,N12-bisethylspermine (BESPM) as a
      substrate. At pH 10, the pH optimum, the limiting rate of reduction of the flavin
      in the absence of oxygen is comparable to the k(cat) value for turnover,
      establishing reduction as rate-limiting. Oxidation of the reduced enzyme is a
      simple second-order reaction. No intermediates are seen in the reductive or
      oxidative half-reactions. The k(cat) value decreases below a pK(a) of 9.0. The
      k(cat)/K(m) value for BESPM exhibits a bell-shaped pH profile, with pK(a) values
      of 9.8 and 10.8. These pK(a) values are assigned to the substrate nitrogens. The
      rate constant for the reaction of the reduced enzyme with oxygen is not affected
      by a pH between 7.5 and 10. Active site residue Tyr430 is conserved in the
      homologous protein monoamine oxidase. Mutation of this residue to phenylalanine
      results in a 6-fold decrease in the k(cat) value and the k(cat)/K(m) value for
      oxygen due to a comparable decrease in the rate constant for flavin reduction.
      This moderate change is not consistent with this residue forming a tyrosyl
      radical during catalysis.

PMID- 15865453
TI  - Reversible photobleaching of enhanced green fluorescent proteins.
AB  - Color variants of green fluorescent protein (GFP) are increasingly used for
      multicolor imaging, fluorescence resonance energy transfer (FRET), and
      fluorescence recovery after photobleaching (FRAP). Here we show that experimental
      settings commonly used in these imaging experiments may induce an as yet
      uncharacterized reversible photobleaching of fluorescent proteins, which is more
      pronounced at acidic pH. Whereas the reversible photobleaching spectrum of eCFP
      corresponds to its absorption spectrum, reversible photobleaching spectra of
      yellow variants resemble absorption spectra of their protonated states.
      Fluorescence intensities recover spontaneously with time constants of 25-58 s.
      The recovery of eCFP can be further accelerated by illumination. The resulting
      steady-state fluorescence reflects a variable equilibrium between reversible
      photobleaching, spontaneous recovery, and light-induced recovery. These processes
      can cause significant artifacts in commonly applied imaging techniques,
      photobleach-based FRET determinations, and FRAP assays.

PMID- 15865454
TI  - Dynamic analysis of articulatory movement using magnetic resonance imaging
      movies: methods and implications in cleft lip and palate.
AB  - OBJECTIVES: To visualize articulatory movement using a magnetic resonance imaging
      (MRI) movie of a subject with cleft lip and palate (clp) and to demonstrate the
      usefulness of this method for studying oropharyngeal function. MATERIAL AND
      METHODS: Dynamic changes in oropharyngeal structures were assessed with an MRI
      movie of a man with cleft lip and palate and in a normal adult male volunteer
      during the articulation of /pa/, /ta/, and /ka/. RESULTS AND CONCLUSIONS:
      Different movement patterns were observed during articulation in the subject with
      CLP compared with the normal volunteer. Posterosuperior movement of the tongue
      and the anterior movement of the posterior pharyngeal wall were clearly
      visualized in the subject with CLP. Thus, MRI movies appear to be a promising
      tool for evaluating speech function in patients with CLP because of their
      noninvasive and nonradiation nature.

PMID- 15865455
TI  - Distraction osteogenesis for bony repair of cleft palate by using persistent
      elastic force: experimental study in dogs.
AB  - OBJECTIVE: The purpose of this study was to investigate the possibility of
      closing a cleft and lengthening the hard palate by the technique of distraction
      osteogenesis with elastic forces and to evaluate the influence of the management
      on the facial structure. DESIGN: Thirty 6-month-old mongrel dogs were assigned
      randomly to two groups with five subgroups for different purpose. INTERVENTIONS:
      An 8- x 25-mm cleft was surgically created in the posterior hard palate in
      experimental and sham control dogs. Bone markers were implanted in the hard
      palate. Osteotomies were carried out followed by the installation of a distractor
      made of NiTi-shape memory alloy. OUTCOME MEASURES: The results were evaluated
      clinically, radiographically, and histologically. Anthropometric data that
      represented the length, width, and height of the maxilla were taken on the dry
      skull of the control and experimental dogs and were analyzed statistically.
      RESULTS: The cleft was closed and the hard palate was lengthened after 2 to 3
      weeks of distraction in all the experimental dogs. New bone formation was found
      at the site of osteotomy. The variables of facial length, height, and width
      showed no significant difference between the two groups (p > .05). The length of
      the hard palate in the experimental group was longer than that in the control
      group (p < .01). CONCLUSION: Distraction osteogenesis with the elastic device of
      NiTi-shape memory alloy is effective for closing the cleft and lengthening the
      hard palate in a canine cleft model. There is no interference on the growth of
      the maxillofacial structures with the technique.

PMID- 15865456
TI  - Effect of an intraoral retrusion plate on maxillary arch dimensions in complete
      bilateral cleft lip and palate patients.
AB  - OBJECTIVE: The aim of this study was to analyze maxillary arch dimensions in
      patients with complete bilateral cleft lip and palate treated with an intraoral
      retrusion plate prior to lip closure. PATIENTS: The effects of the intraoral
      retrusion plate were evaluated on serially obtained maxillary casts of 14
      patients with complete bilateral cleft lip and palate. RESULTS: The Student's t
      test for dependent observations showed a significant decrease in distance between
      the premaxilla and the cleft lateral segments during active treatment. This
      decrease correlated with an increase in deviation of the premaxilla in relation
      to the vomer. For each millimeter decrease in distance between the premaxilla and
      the cleft lateral segments, an average increase in deviation of 4.0 degrees was
      found. Left and right cleft widths decreased significantly, premaxillary width
      increased significantly, and transverse dimensions did not change significantly.
      CONCLUSION: From this study it can be concluded that active presurgical treatment
      with an intraoral retrusion plate induces a significant decrease in distance
      between the premaxilla and the lateral segments. This decrease is frequently
      accompanied by an increase in deviation of the premaxilla relative to the vomer.

PMID- 15865457
TI  - Visual and statistical modeling of facial movement in patients with cleft lip and
      palate.
AB  - OBJECTIVE: To analyze and display facial movement data from noncleft subjects and
      from patients with cleft lip and palate by using a new dynamic approach. The
      hypothesis was that there are differences in facial movement between the patients
      with cleft lip and palate and the noncleft subjects. SETTING: Subjects were
      recruited from the University of North Carolina School of Dentistry Orthodontic
      and Craniofacial Clinics. PATIENTS, PARTICIPANTS: Sixteen patients with cleft lip
      and palate and eight noncleft "control" subjects. INTERVENTIONS: Video recordings
      and measurements in three dimensions of facial movement. MAIN OUTCOME MEASURES:
      Principal component (PC) scores for each of six animations or movements and
      dynamic modeling of mean animations. STATISTICS: Multivariate statistics were
      used to test for significant differences in the PC mean scores between the
      patient groups and the noncleft groups. RESULTS: No statistically significant
      differences were found in PC mean scores between the patient groups and the
      noncleft groups; however, the variability of the effect of clefting on the soft
      tissues during animation was noted when the noncleft data were used to establish
      a "normal" scale of movement. Compensatory movements were seen in some of the
      patients with cleft lip and palate, and the compensation was not unidirectional.
      CONCLUSION: Measures of mean movement differences as summarized by PC scores
      between patients with cleft lip and palate and noncleft subjects may be
      misleading because of extreme variations about the mean in the patient group that
      may neutralize group differences. It may be more appropriate to compare patients
      to a noncleft normal scale of movement.

PMID- 15865458
TI  - Changing lifestyles and oral clefts occurrence in Denmark.
AB  - OBJECTIVE: The aim of this project was to assess whether any changes in the birth
      prevalence of cleft lip with/without cleft palate (CL[P]) occurred in Denmark
      during the period 1988 through 2001. In this period an official recommendation of
      a supplementation of folic acid to pregnant women was introduced; furthermore,
      smoking among pregnant women decreased considerably. DESIGN AND SETTINGS: There
      are few places in which ecological studies of oral clefts are possible. Denmark
      provides a particularly good setting for this kind of study because of a high
      ascertainment and a centralized registration of subjects with cleft over the last
      65 years. PARTICIPANTS: Cleft occurrence in Denmark from 1936 to 1987 has
      previously been reported. Here we extend the study to include all live-born
      children with oral clefts born in Denmark in 1988 through 2001. Among a total of
      992,727 live births, 1332 children with CL(P) were born during this period.
      RESULTS AND CONCLUSIONS: The birth prevalence of CL(P) in Denmark has previously
      been found to be constant in the period 1962 through 1987, with a frequency of
      1.4 to 1.5 per 1000 live births. This study showed a similar occurrence in 1988
      through 2001 (birth prevalence = 1.44 per 1000 live births, 95% confidence
      interval = 1.37 to 1.52). The introduction of folic acid and the decrease in
      smoking prevalence among pregnant women do not seem to have reduced the birth
      prevalence. This may be due to noncompliance with the folic acid recommendation
      and/or only a weak causal association between folic acid and smoking and
      occurrence of CL(P).

PMID- 15865459
TI  - Health-related quality of life of children aged 11 to 14 years with orofacial
      conditions.
AB  - OBJECTIVE: To assess the health-related quality of life (HRQoL) of 11- to 14-year
      old children with orofacial conditions. DESIGN: Thirty-nine patients with
      orofacial conditions were compared with 32 patients with dental caries. OUTCOME
      MEASURE: The multidimensional 37-item Child Perceptions Questionnaire for 11- to
      14-year-old children (CPQ(11-14)). This forms one component of the Child Oral
      Health Quality of Life Questionnaire. RESULTS: The orofacial group had slightly
      higher scores on the CPQ(11-14) than the dental group (p < .05). The scores were
      slightly to moderately higher on the functional limitations (p < .01) and social
      well-being (p < .01) domains. The groups did not differ with respect to oral
      symptoms or emotional well-being. Mouth breathing, problems with speech, missing
      school, being teased, and being asked questions about their condition were the
      only issues reported more frequently by the orofacial group (p < .01). There was
      no evidence of social inhibition or withdrawal in the orofacial group. The
      children with orofacial conditions rated their oral health better than the
      children with dental decay (p < .05). In both groups, the majority of children
      reported that their condition had little impact on their life overall.
      CONCLUSIONS: Based on CPQ(11-14) scores, there were few differences in the HRQoL
      of 11- to 14-year-old children with orofacial conditions, compared with children
      with dental caries. This suggests that the majority of these children are well
      adjusted and able to cope with the adversities they experience as a result of
      their conditions. This may reflect the quality of the team approach used at the
      treatment setting at which they were recruited.

PMID- 15865460
TI  - No evidence for linkage and association between 4q microsatellite markers and
      nonsyndromic cleft lip and palate in chilean case-parents trios.
AB  - OBJECTIVE: Nonsyndromic cleft lip/palate (NSCLP) has the characteristics of a
      complex genetic trait. Linkage and association studies have suggested that one or
      more clefting loci may be located on chromosome 4q. The goal of this study was to
      evaluate the possible linkage and association due to linkage disequilibrium
      between five microsatellite markers located on 4q28 to 4q33 and NSCLP, using the
      case-parent trio design. SUBJECTS AND METHODS: A total of 56 Chilean families (32
      simplex and 24 multiplex) were recruited. Microsatellite markers were analyzed
      using polymerase chain reaction with fluorescent-labeled forward primers,
      followed by electrophoresis on a laser-fluorescent sequencer. Case-parents trios
      were ascertained to assess linkage and linkage disequilibrium through a
      multistage procedure. Transmission disequilibrium tests for multiple alleles were
      carried out to assess the statistical significance of 4q28 to 4q33 microsatellite
      markers. RESULTS: Only weak evidence for linkage was obtained for the FGA marker
      (asymptotic uncorrected p value = .08 and empirical p value = .05). Only the FGA
      and UCP1 markers were selected for association analysis in trios, with unrelated
      cases achieving a nearly significant result for the UCP1 marker (asymptotic
      uncorrected p value = .07 and empirical p value = .19). CONCLUSION: Though the
      FGA and UCP1 markers showed nearly significant p values for linkage and
      association, respectively, the results of the present study provided insufficient
      evidence of the existence of a major susceptibility locus in the 4q region that
      was analyzed in the present study.

PMID- 15865461
TI  - The bacteriology of children before primary cleft lip and palate surgery.
AB  - OBJECTIVE: Bacterial infections can complicate any surgery. Knowledge of
      potentially pathogenic bacterial flora in children with cleft lip and palate
      allows appropriate risk management, including the need for prophylactic
      antibiotics. This project reviewed the bacteriology of children before primary
      cleft lip and palate surgery. DESIGN: A retrospective study of the results of
      nose, throat, and ear microbiological swabs taken from children, aged 1 to 26
      months, before repair of primary cleft lip, cleft palate, or both was carried
      out. Swabs with Staphylococcus aureus and beta-hemolytic streptococcus were
      considered positive. RESULTS: From October 1987 to May 2002, 321 primary cleft
      lip or palate operations were performed in 250 patients. Results from 326 sets of
      preoperative swabs were available, including five repeat sets from patients whose
      operations were postponed. There were 235 (72.1%) negative sets and 91 (27.9%)
      positive sets. Of the positive swabs, 86 sets grew S. aureus, and 10 sets grew
      beta-hemolytic streptococcus. CONCLUSIONS: Children with unrepaired cleft lip and
      palate have a significant risk of carrying S. aureus and a small risk of carrying
      beta-hemolytic streptococci. These risks need to be considered when deciding on
      protocols for preoperative bacteriology tests and prophylactic antibiotics.

PMID- 15865462
TI  - Study of viridans streptococci and Staphylococcus species in cleft lip and palate
      patients before and after surgery.
AB  - OBJECTIVE: To determine the effect of surgery on types and colony count of
      Streptococcus and Staphylococcus species in cleft lip and palate (CLP) patients.
      DESIGN: Saliva samples were collected after the morning meal by placing a sterile
      cotton swab in the vestibule of the oral cavity from cleft lip and palate
      patients immediately preoperative and 12 weeks postoperative. Normal children
      were examined as a control group. Samples were cultured; Staphylococcus and
      Streptococcus isolates were identified and quantified. PATIENTS: Fifteen cleft
      lip and palate patients and 22 normal children, aged 3 to 39 months were
      examined. RESULTS: Streptococcus mitis biovar 1, Streptococcus salivarius and
      Streptococcus oralis of the viridans group of streptococci were the most commonly
      found in normal children, as well as in cleft lip and palate children. In the
      cleft lip and palate group, mean streptococcal count was 32.41 (29.80) and 46.46
      (42.80) in the pre- and postoperative periods, respectively; in the normal group,
      the count was 20.93 (27.93) and 49.92 (34.72) at 0 week and 12 weeks,
      respectively. Staphylococcus aureus was the most common Staphylococcus species
      found in CLP patients, representing 47.4% postoperatively. In the cleft lip and
      palate children, mean staphylococcal count was 5.34 (8.13) and 0.56 (0.92) in the
      pre- and postoperative periods, respectively; in normal children, the count was
      0.82 (1.98) and 0.60 (2.55) at 0 and 12 weeks, respectively. The differences were
      statistically significant only for the staphylococcal count between pre- and
      postoperative periods in children with cleft lip and palate as tested by analysis
      of variance (p < .05). CONCLUSIONS: Cleft lip and palate patients had more
      colonization by S. aureus compared with normal children, and the colony count
      decreased significantly following surgical repair of the cleft lip and palate.

PMID- 15865463
TI  - Audiological status of Chinese patients with cleft lip/palate.
AB  - OBJECTIVE: To review the audiological and otoscopic status of Chinese children
      and young adults seen at a cleft lip and palate clinic in Hong Kong and compare
      with previous studies of Western clinical populations. DESIGN: The hearing health
      status of the patients was analyzed on the basis of the results of their
      otoscopic, pure tone audiometric, and tympanometric examinations. The patients'
      sex, age, race, and type of cleft pathology were examined for their potential
      relationship to hearing health status. PARTICIPANTS: The records of 180
      predominantly Chinese patients attending the Cleft Lip and Palate Centre, Prince
      Philip Dental Hospital/University of Hong Kong from July 1977 to December 1999
      were reviewed. RESULTS AND CONCLUSION: The results indicated 13.4% of patient
      ears failed the audiometric screening and 23.7% of patient ears yielded abnormal
      tympanometric results. Patients' sex, age, and type of cleft pathology were found
      not to be related to hearing screening results. The prevalence of hearing
      disorder was in contrast with Western studies that show a much higher rate of
      audiological problems in children and young adults with cleft lip/palate. Racial
      factors were considered to be possible reasons for this disparity. Other factors,
      such as timely medical and surgical intervention, including early cleft palate
      repair and the insertion of ventilation tubes in cases of middle ear effusion, do
      not convincingly account for the study findings.

PMID- 15865464
TI  - Immediate and sustained changes in tongue movement with an experimental palatal
      "fistula": a case study.
AB  - OBJECTIVE: To determine the immediate and longer-term effect(s) on tongue
      movement following the placement of an experimental opening through a palatal
      obturator (replicate of subject's prosthesis) worn by an adult male with an
      unrepaired cleft of the hard and soft palate. METHODS: Tongue movements
      associated with an anterior experimental opening of 20 mm(2) were examined under
      three conditions: a control condition in which the subject wore the experimental
      obturator completely occluded, a condition immediately after drilling the
      experimental openings through the obturator, and a condition after 5 days in
      which the subject wore the experimental obturator with the experimental opening.
      An Electromagnetic Articulograph was used for obtaining tongue movements during
      speech. RESULTS: The findings partly revealed that the immediate introduction of
      a perturbation to the speech system (experimental fistula) had a temporary effect
      on tongue movement. After sustained perturbation (for 5 days), the system
      normalized (going back toward control condition's behavior). Perceptual data were
      consistent with kinematic tongue movement direction in most of the cases.
      CONCLUSIONS: Although the immediate response can be interpreted as indicative of
      the subject's attempts to move the tongue toward the opening to compensate for
      air loss, the findings following a sustained perturbation indicate that with
      time, other physiological adjustments (such as respiratory adjustments, for
      example) may help reestablish the requirements of a pressure-regulating system.

PMID- 15865465
TI  - Intraoral air pressure discrimination under conditions of experimental
      velopharyngeal insufficiency.
AB  - OBJECTIVE: This study assessed a single subject's ability to detect the
      difference limen (DLs) for his self-generated intraoral air pressure while his
      oral and nasal cavities were experimentally coupled. METHOD: The subject, a 46
      year-old man, uses a speech bulb prosthesis to cover an unrepaired cleft of his
      hard and soft palates. The subject's oral and nasal cavities were experimentally
      coupled by drilling different size holes through the speech-bulb component of the
      prosthesis to approximate conditions of velopharyngeal insufficiency. There were
      four hole-size conditions (10, 15, 20, and 30 mm(2)), a no-prosthesis condition,
      and pre- and postbaseline conditions with the prosthesis intact. The subject blew
      into a tube connected to a pressure transducer and was presented with a series of
      paired pressure loads. The first pressure load of each pair was the referent (1,
      3, or 5 cm H(2)O), and the second was a preselected comparator load of a
      different amount. The subject blew into the tube with sufficient force to center
      the voltage meter's needle at the zero mark. The subject then reported whether
      the second pressure load required more, less, or equal breath pressure, compared
      with the referent pressure load of that pair. RESULTS: Size of the hole coupling
      the oral/nasal cavities did not significantly affect the subject's difference
      limen. CONCLUSION: Experimental coupling of the oral/nasal cavities did not
      affect this subject's ability to detect differences in his self-generated
      intraoral air pressure.

PMID- 15865466
TI  - Oral disease status of a sample of Jordanian people ages 10 to 28 with cleft lip
      and palate.
AB  - OBJECTIVE: To determine the levels of periodontal disease and dental caries in
      subjects with cleft lip and palate and to compare them with matched noncleft
      control subjects. DESIGN: A total of 32 subjects with cleft lip and palate, ages
      10 to 28 years, and a similar number of noncleft control subjects were examined
      for plaque biofilm deposits, gingivitis, periodontitis, and dental caries by
      using the Silness and Loe plaque index (PI), Loe and Silness gingival index (GI),
      probing pocket depth (PPD), and the decayed-missing-filled-teeth (DMFT) index,
      respectively. SETTING: Faculty of Dentistry, Jordan University of Science and
      Technology, and Prince Rashed Hospital, Royal Medical Services, northern Jordan.
      RESULTS: Scores for PI, GI, PPD, and DMFT were significantly higher in subjects
      with cleft lip and palate than in control subjects. CONCLUSION: Subjects with
      cleft lip and palate are at an increased risk for dental caries and periodontal
      disease when compared with a noncleft population.

PMID- 15865467
TI  - Clinical study on eruption of permanent canines after secondary alveolar bone
      grafting.
AB  - OBJECTIVE: Eruption of cleft-associated permanent canines was studied in 190
      patients with unilateral cleft lip/palate and whose permanent canines had not
      erupted at the time of alveolar bone grafting. In 162 of these patients, width of
      bone defect was compared between patients who underwent surgical exposure of
      canines and those whose canines erupted naturally. RESULTS: Cleft-associated
      canines naturally erupted after bone grafting in 150 patients (78.9%) and
      required surgical exposure in 36 patients (18.9%). Cleft-associated canines had
      not yet erupted in two patients. Two patients were lost to follow-up. Nasal-side
      bone defects were significantly wider in patients who underwent surgical exposure
      of cleft-associated permanent canines than in those whose cleft-associated
      permanent canines erupted naturally. CONCLUSIONS: The present results suggest
      that nasal-side cleft width is related to the need for surgical exposure of
      permanent canines in children with cleft lip/palate.

PMID- 15865468
TI  - Congenitally missing teeth in the Israeli cleft population.
AB  - OBJECTIVE: The purpose of the study was to determine the prevalence of
      congenitally missing teeth in a group of Israeli children with various types of
      clefts. DESIGN: Prevalence of congenitally missing teeth was determined for 179
      children with cleft lip, cleft lip and alveolar ridge, cleft lip and palate, and
      cleft palate. Subgroupings were assessed according to patient sex, origin, cleft
      type, tooth type, and the side of hypodontia. The diagnosis of congenitally
      missing teeth (CMT) was based on initial and follow-up panoramic roentgenograms.
      In case of doubt, occlusal or periapical roentgenograms as well as clinical
      dental photographs were also used. SETTING: Data collection was conducted at the
      Rambam Medical Center, Orthodontic and Craniofacial Unit, Haifa, Israel. RESULTS:
      In the total cleft group, 67.6% of the patients presented with hypodontia,
      totaling 246 missing teeth. A statistically significant difference was found in
      the distribution of patients with CMT of Jewish and minority origin according to
      sex. Cleft lip and palate was the most frequently affected group in which 195
      teeth were missing. The most frequently missing tooth among the cleft population
      was the maxillary incisor. The order of frequency of the other missing teeth was
      the same as in the normal population. Hypodontia and malformations of permanent
      teeth were most common on the cleft side. CONCLUSION: The frequency of CMT in the
      Israeli cleft population studied was higher than in the intact population. This
      confirms findings in other populations worldwide.

PMID- 15865469
TI  - Rigid external distraction using skeletal anchorage to cleft maxilla united with
      alveolar bone grafting.
AB  - OBJECTIVE: Documentation of the application of maxillary distraction osteogenesis
      using rigid external distraction (RED) with skeletal anchorage combined with
      predistraction alveolar bone grafting (ABG) in cleft maxilla. DESIGN: Case
      report. PATIENT: A patient with numerous congenital missing teeth and severe
      maxillary deficiency related to complete bilateral cleft lip and palate with
      large alveolar bone defect. INTERVENTION: The patient received preoperative
      orthodontic treatment, predistraction ABG, and maxillary distraction osteogenesis
      using RED with skeletal anchorage. RESULTS: Predistraction ABG completely united
      the cleft maxilla. The united maxilla was successfully advanced by the RED system
      with skeletal anchorage, despite unsound dentition with numerous congenital
      missing teeth. CONCLUSION: The present study demonstrates that the combination of
      predistraction ABG and RED system with skeletal anchorage is effective for the
      treatment of severe maxillary deficiency related to complete bilateral cleft lip
      and palate with large bone defect and numerous congenital missing teeth.

PMID- 15865470
TI  - A case of mitochondrial myopathy and cleft palate.
AB  - OBJECTIVE: To present a child born with both mitochondrial myopathy and cleft
      palate, outlining medical complications of this dual diagnosis-the first reported
      case in English literature. METHODS: A preterm Caucasian boy presented to the
      cleft palate clinic at birth for evaluation of a secondary cleft palate. Multiple
      anomalies were also identified, including rib fusions, ventricular septal
      dyskinesis, and mild hypotonia. Initial chromosome studies were unremarkable.
      RESULTS: After a multidisciplinary preoperative clearance at 11 months old, the
      infant underwent palatoplasty and muscle biopsy for evaluation of hypotonia. Upon
      extubation, he became apneic and unresponsive to anticholinesterase reversals. He
      was reintubated. The next morning, he was extubated uneventfully and was
      discharged home on postoperative day 2 (POD2). On POD7, he returned with signs of
      bronchitis, thereby prompting immediate reevaluation and treatment by his primary
      pediatrician. On POD13, he presented to an outlying emergency department with
      cyanosis and poor respiratory drive. Before intubation, he received a
      depolarizing muscle relaxation; cardiac arrest ensued and resuscitation was
      unsuccessful. Pathology from the muscle biopsy and postmortem examination
      ultimately supported mitochondrial myopathy with dilated cardiomyopathy.
      CONCLUSION: Mitochondrial myopathies are rare disorders suspected in patients
      demonstrating developmental delays, hypotonia, cardiomyopathy, conduction system
      defects, or genetic mutations. In these patients, postoperative complications can
      be lethal, especially when compounded (e.g., anesthetic drug reactions,
      respiratory compromise, surgical stress, and postoperative infections). General
      discussion and specific recommendations are provided.

PMID- 15865471
TI  - Imaging of photodynamically generated singlet oxygen luminescence in vivo.
AB  - We describe a novel scanning-laser system for imaging type-II photodynamically
      generated singlet oxygen (1O2[1delta(g)]) luminescence and demonstrate it in vivo
      in an intradermal tumor model in mice. We verify the strong oxygen-dependence of
      the signal and show that the images are near the practical resolution limit.

PMID- 15865472
TI  - Proposals for improvement of emergency rural health care.
AB  - Universal healthcare coverage is a right, and that includes emergency health
      care. The community expects such requirements to be within their reach, including
      all human and technological resources necessary for rapid and high-quality health
      assistance in an emergency. Access to and delivery of emergency care in rural
      areas is recognized as more difficult than that in urban areas. In this report,
      following the EURIPA meeting in June 2004, the authors determine the problems of
      dealing with emergencies in the rural healthcare context, and also make proposals
      for improvement.

PMID- 15865473
TI  - Rural nursing unit managers: education and support for the role.
AB  - INTRODUCTION: Nursing unit managers (NUMs) occupy the often unenviable position
      of first-line management in many health services in Australia. As such, their
      role is complex and multifaceted requiring an intertwining of their clinical and
      managerial responsibilities. While there is an abundance of studies that explore
      and describe the various management roles in many professions and industries,
      little is known about the experiences of nurses as managers, particularly in
      rural settings. This article focuses on the education and support needs of rural
      nursing unit managers. METHODS: A qualitative study design was used to explore
      the stories of a number of nursing unit managers in rural New South Wales,
      Australia. Data was collected using semi-structured individual interviews. Data
      was analysed using a voice-relational method as a framework for more clearly
      hearing the voices of participants. This method of data analysis is particularly
      useful for hearing from those who do not usually have a 'strong' voice, for
      gaining an understanding of the context of the interviews, and for acknowledging
      the role of the researcher in the research process. All NUMs employed in a single
      regional health authority in rural Australia were invited to participate.
      RESULTS: Out of 42 NUMs in the region, 20 agreed to be interviewed. Nursing unit
      managers were asked to reflect on their experiences prior to and during the early
      days within the position. In summary, all the NUMs: believed they were promoted
      because of their clinical expertise; felt unprepared for the managerial and
      administrative aspects of their role; continued to identify as nurses rather than
      as managers; found the role isolated them from their former peer group. Those
      employed in small facilities had limited opportunities for education and peer
      support. CONCLUSIONS: Based on the NUMs' experiences and suggestions, the
      following information would have helped them to cope with the demands of their
      new role: information and discussions about the role expectations of first-line
      manager, from both an employee and employer perspective; human resource and
      financial management skill development; leadership skills; negotiation and
      conflict resolution; a clear and realistic role description.

PMID- 15865474
TI  - Development of a questionnaire measuring student attitudes to working and living
      in rural areas.
AB  - INTRODUCTION: Student attachments in rural locations have been instigated, in
      part to foster positive attitudes to rural practice and encourage rural
      recruitment. Based on medical and allied health literature, it was hypothesised
      that students' attitudes to rural practice and rural life encompasses the
      following three dimensions: (1) community and social issues; (2) family and
      personal issues; and (3) professional issues. However, there are limited studies
      assessing attitudinal change before and after rural placement and no valid and
      reliable tools which examine change across all three dimensions. This article
      reports on the development, reliability and validity of such a tool to fill this
      gap in the rural health research literature. METHODS: Students who undertook a
      rural placement in South Australia or a rural placement organised by the Mt Isa
      Centre for Rural and Remote Health in Queensland, Australia, during 2001 were
      invited to complete a pre- and post-placement questionnaire (n = 243). The
      response rate for the pre-placement questionnaire was 74.9% (n = 182) and 50.2%
      (n = 122) for the post-placement questionnaire. A literature review informed the
      content of the initial questionnaire, which consisted of a series of statements
      to which respondents were instructed to indicate how strongly they agreed or
      disagreed on a Likert scale of one to six. The assessment of validity and
      reliability of the questionnaire involved three main processes. Content validity
      was assessed by discussion and rating by academics and students, resulting in 18
      questionnaire items. Exploratory factor analysis was used to provide evidence of
      construct validity. The internal consistency reliability of the questionnaire was
      assessed using Cronbach's alpha. RESULTS: The Cronbach's alpha coefficient for
      the post-questionnaire was 0.68, acceptable for newly developed scales.
      Exploratory factor analysis and varimax rotation was conducted for pre- and post
      placement (n = 110) questionnaires. The pre-placement questionnaire did not lend
      itself to logical interpretation, probably due to the diverse attitudes students
      may have pre-rural placement. However the factors on the post-placement
      questionnaire were interpretable. The Scree Plot indicated four factors,
      explaining 60.82% of the total variance. The factors were rotated using the
      normalised varimax rotation method. The factors extracted were: (1) friendliness
      and support in rural areas; (2) isolation and socialisation problems associated
      with living and working in rural areas; (3) enjoyable aspects of living in a
      rural area; and (4) opportunities that working in a rural area provides.
      CONCLUSIONS: Analysis of the Student Attitudes to Rural Practice and Life
      Questionnaire provides evidence of validity. The study identified four factors
      associated with student attitudes to living and working in rural areas, which
      differ from those hypothesised. The main deviation was Factor 2, grouping all the
      negative aspects of isolation and socialisation in a rural area. The resulting
      factors provide a more integrated reflection of the rural experience, rather than
      the rigid categorisation of professional, social and personal issues. Reliability
      was found to be adequate. The questionnaire is able to measure student attitudes
      to rural practice and rural life, and may be used to evaluate the impact of rural
      placement on student attitudes.

PMID- 15865475
TI  - Invisibility, safety and psycho-social distress among same-sex attracted women in
      rural South Australia.
AB  - INTRODUCTION: Available work from North America indicates that same-sex attracted
      (SSA) individuals enjoy aspects of rural life but nonetheless report encountering
      homophobia and experiencing isolation from SSA networks. The experience of
      prejudice and social isolation are often associated with psycho-social distress
      among the general population of same-sex attracted individuals. Little is known
      of how SSA women experience life in rural areas of Australia and how this
      influences their psycho-social wellbeing. METHODS: This was a small-scale
      qualitative study using guided interviews to explore the experience of SSA women
      living in rural areas of South Australia. Seven women identifying as same-sex
      attracted were interviewed. In addition, a woman who provides a counseling and
      support service for same-sex attracted women was also interviewed. All interviews
      were audiotaped and transcribed verbatim and were then analysed for emergent
      themes. Summaries of the interviews, based on the emergent themes, were sent to
      all interviewees so that they could verify or challenge the validity of the
      emergent themes, as well as to allow them to remove any information they felt
      might identify them. RESULTS: Most women had felt 'different' while growing up;
      almost unanimously describing themselves as having been 'tomboys'. However, the
      lack of visible SSA role models in rural areas, together with a lack of SSA
      social networks, did not allow some of the women to identify and name their same
      sex attraction. For many of the women in this study, it was visits to the state
      capital, where they had the opportunity to meet other SSA women, which
      precipitated them identifying themselves as same-sex attracted. In light of this
      new knowledge, some women denied their same-sex attraction and entered into
      heterosexual relationships, often entailing marriage. Other women entered same
      sex relationships but tried to keep them invisible within their communities.
      Rural communities are frequently close-knit environments, where 'everybody knows
      everybody'. In such settings, much of the conduct of daily life is visible to
      other community members and may be closely scrutinized. In such locations, women
      initially try to keep their same sex attraction invisible. Women rarely comment
      on the threat of violence that underpins the attempt to keep same-sex identity or
      relationships secret. Nevertheless, even while it remains a largely unarticulated
      factor, it was a powerful one fueling the maintenance of their invisibility. Fear
      of violence ranges from the threat of overt physical violence to more commonly
      voiced concerns over 'mundane' harassment. Fear of social violence, in the form
      of rejection and ostracism, is the most frequently nominated factor motivating
      women to keep same-sex attraction invisible in rural settings. While keeping
      their same-sex identity and relationships invisible offers women some safety from
      physical and social violence, it may pose dangers for their psycho-social well
      being. Trying to keep SSA relationships invisible within communities involves
      women censoring their behaviour while in public. Invisibility also gives rise to
      isolation, since women do not have the opportunity to form same-sex attracted
      social networks. Furthermore, some women experience great psycho-social distress
      as their awareness of their same-sex attraction becomes increasingly incongruent
      with the established pattern of their lives. Women find it very difficult to seek
      appropriate forms of help if they do experience psycho-social problems. Concerns
      over confidentiality means that women are extremely reluctant to seek help and
      support locally. Distance is a powerful mediating factor in both women's
      experience of distress and their capacity to seek help to ameliorate it. For
      women who live in closer proximity to the state capital, the capacity to meet
      other SSA women and engage in same-sex attracted social activities helps ease
      their sense of difference and isolation. Likewise, should they wish to utilize
      counseling or support services, it is relatively easy for them to do so. However,
      women living at greater distances from a capital city experience greater
      isolation and loneliness. Moreover, their ability to confidentially access
      appropriate services is markedly curtailed. CONCLUSIONS: Same-sex attracted women
      living in rural areas need social contact with other SSA women, where their
      safety and confidentiality can be assured. They also need access to safe,
      confidential and appropriate services. Telephone and internet services are one
      way of anonymously and confidentially giving women access to information and
      support. Peer support networks, internet and telephone networks need to be
      further developed. Ways in which specialist gay and lesbian services and locally
      based health and human services could collaborate to provide accessible and
      acceptable services and to help women develop safe and confidential social
      networks need to be identified and trialled.

PMID- 15865476
TI  - Life-style activities in older people without intellectual impairment: a
      population-based study.
AB  - INTRODUCTION: Activities of daily living are important indicators of the
      functional status and wellbeing of older persons. Data derived from life-style
      activities of the community at large are important for such diverse purposes as
      characterising the individual's ability for independent living, studying normal
      ageing, or investigating social factors in rehabilitation. Our objective was to
      determine patterns in the life-style activities of people aged 65 years and older
      who had no intellectual impairment. METHODS: The article is a cross-sectional
      study of a population-based sample. Eligible people were non-institutionalised
      and aged 65 years or older, resident in the province of Guadalajara, Spain, and
      without intellectual impairment as assessed by the 10-item Short Portable Mental
      Status Questionnaire. Questionnaires were administered by trained interviewers
      and included questions about the daily activities of the Adelaide Activities
      Profile (AAP), distributed among the four categories of domestic chores,
      household maintenance, service to others, and social activities. Each item was
      rated 0 = absent or 1 = present, and total scores ranged from 0 to 19. RESULTS:
      The sample included 192 men and 196 women from rural areas and 172 men and 220
      women from urban areas. In the category of domestic chores, mean ratings for
      women (4.56, 95% CI 4.30 to 4.84) were significantly higher (p <0.05) than for
      men (1.36, 95% CI 1.11 to 1.62) both in urban and rural areas, except in the
      oldest age group (> or =85 years). In the subscale of household maintenance, also
      except for group of > or =85 years, men rated significantly higher (3.31, 95% CI
      3.11 to 3.53) than women (2.34, 95% CI 2.21 to 2.47), independent of the place of
      residence. Women scored significantly higher than men in activities associated
      with service to others. Men younger than 80 years from rural areas were
      significantly more involved in social activities than women. In urban areas both
      sexes scored similarly in social activities CONCLUSION: The differences found
      among the AAP scales in relation to gender was a clear indication of the well
      established roles for men and women in our sociocultural context. The 19-item
      version of the AAP scale is a valuable survey instrument as an objective guide
      for studying activities related to life-style in community settings.

PMID- 15865477
TI  - 'Did everybody get that?' The challenges of international teleconferencing.
AB  - Countless hours and dollars are frittered away during teleconferences. This
      situation is greatly magnified when spread across international boundaries. Some
      simple steps can reduce this waste. Careful attention should be paid to such
      issues as time zones, appropriate telephone etiquette and equipment, sensible
      meeting management, careful use of additional data files and restrained use of
      new technology in some areas. Based on our group's extensive experience, we have
      collected some useful tips and resources on how to reduce your costs and
      frustrations.

PMID- 15865478
TI  - Reviewing respiratory disease burden in rural India: household environment
      matters.

PMID- 15865479
TI  - Sustaining the rural primary healthcare workforce: survey of healthcare
      professionals in the Scottish Highlands.
AB  - INTRODUCTION: Many westernised countries face ongoing difficulties in the
      recruitment and retention of health professionals in remote and rural
      communities. Predictors of rural working have been identified by the
      international literature, and include: the individual having been born or
      educated in a rural location; exposure to rural healthcare during training;
      access to continuing professional education; good relationships with peers;
      spousal contentedness; adoption of a rural 'lifestyle'; successful integration
      into local communities; and educational opportunities for children. However,
      those themes remain unverified in the UK. The present study aimed to ascertain
      whether the internationally identified determinants of recruitment and retention
      of the rural health workforce apply in the Highlands of Scotland, which includes
      the most sparsely populated area of the UK mainland, as well as an urban area.
      METHODS: In 2003, a questionnaire was sent to all 2070 primary healthcare
      professionals working in the Highlands (which makes up one-third of Scotland's
      land area (9800 square miles) and has just 4% of the country's population
      (209,000)). Approximately one-quarter of the Highland's population live in
      Inverness. The area is ideal for investigating the rural workforce due to its
      population sparsity and the inclusion of small towns and Inverness, allowing
      urban/rural comparisons. The questionnaire asked about places of birth and
      education; intentions to stay/leave current location; professional isolation;
      access to amenities; and perceptions of belonging to the local community.
      RESULTS: The response rate was 53%. Compared with respondents working in urban
      areas, those working in rural areas were more likely to have been born in rural
      areas. Professionals living in rural areas were more likely to have been born
      outside Scotland and to have completed their secondary education and professional
      training outside Scotland, compared with those living in urban areas.
      Approximately one-third (34%) had lived in their current location for more than
      10 years, and that proportion was higher for the urban group compared with rural
      dwellers. Similarly, the urban dwellers were more likely to have been in their
      current job for more than 10 years. Respondents' perceptions of being isolated,
      of their caring roles extending beyond their work; and of an inability to get
      away from work for holidays and study leave, were more common among rural
      dwellers. Eighty-one percent of respondents said that they felt part of their
      community and that proportion was higher for those working in rural areas, than
      for urban residents. Respondents indicated their perceived ease of access to five
      amenities and services: children's education (preschool, primary and secondary);
      access to a job for spouse; and health care. With the one exception of access to
      primary education, access was perceived to be most difficult by the professionals
      working in rural areas. CONCLUSIONS: Our survey confirms, in the UK, the
      association between rural background and rural working, and highlights the
      contribution of healthcare professionals from other parts of the UK to the
      Scottish rural workforce. It also suggests that professional isolation and
      perceived lack of access to amenities are important issues for those working in
      rural areas.

PMID- 15865480
TI  - Cutting costs at the expense of rural communities -- is it all dollars and no
      sense?

PMID- 15865482
TI  - Retaining rural medical practitioners: time for a new paradigm?

PMID- 15865484
TI  - Unexpected lessons from academic medicine.

PMID- 15865485
TI  - The scientific value of Ayurveda.

PMID- 15865486
TI  - Duty, curiosity, and enlightened self-interest: what makes acupuncture
      practitioners participate in national research studies?

PMID- 15865487
TI  - Attitudes about acupuncture and homeopathy among doctors in research positions: a
      survey.

PMID- 15865488
TI  - The dynamics of life: imaging changing patterns of air surrounding material and
      biological systems with dynamic interferometry.

PMID- 15865489
TI  - Efficacy of yoga on pregnancy outcome.
AB  - OBJECTIVE: To study the efficacy of yoga on pregnancy outcomes. DESIGN AND
      SETTING: Three hundred thirty five (335) women attending the antenatal clinic at
      Gunasheela Surgical and Maternity Hospital in Bangalore, India, were enrolled
      between 18 and 20 weeks of pregnancy in a prospective, matched, observational
      study; 169 women in the yoga group and 166 women in the control group. METHODS:
      Women were matched for age, parity, body weight, and Doppler velocimetry scores
      of umbilical and uterine arteries. Yoga practices, including physical postures,
      breathing, and meditation were practiced by the yoga group one hour daily, from
      the date of entry into the study until delivery. The control group walked 30
      minutes twice a day (standard obstetric advice) during the study period.
      Compliance in both groups was ensured by frequent telephone calls and strict
      maintenance of an activity diary. MAIN OUTCOMES: Birth weight and gestational age
      at delivery were primary outcomes. RESULTS: The number of babies with birth
      weight > or = 2500 grams was significantly higher (p < 0.01) in the yoga group.
      Preterm labor was significantly lower (p < 0.0006) in the yoga group.
      Complications such as isolated intrauterine growth retardation (IUGR) (p < 0.003)
      and pregnancy-induced hypertension (PIH) with associated IUGR (p < 0.025) were
      also significantly lower in the yoga group. There were no significant adverse
      effects noted in the yoga group. CONCLUSIONS: An integrated approach to yoga
      during pregnancy is safe. It improves birth weight, decreases preterm labor, and
      decreases IUGR either in isolation or associated with PIH, with no increased
      complications.

PMID- 15865490
TI  - The chinese herbal medicine Tien-Hsien liquid inhibits cell growth and induces
      apoptosis in a wide variety of human cancer cells.
AB  - OBJECTIVE: Tien-Hsien liquid (THL) is a commercially available Chinese herbal
      mixture that has been used as an anticancer dietary supplement for more than 10
      years. We recently showed that THL has strong immunomodulatory effects on
      peripheral blood mononuclear cells (PBMC) and T cells. To investigate the
      antitumor activity of THL further, we sought to test whether THL could induce
      apoptosis in various human cancer cell lines based on the fact that THL contains
      several components with tumor killing functions. DESIGN: The growth inhibitory
      effect of THL on human cervical carcinoma C-33A cells, human lung carcinoma H1299
      cells, and human PBMC was assessed by counting viable cells using the trypan blue
      dye exclusion method. The apoptosis-inducing activity of THL in H1299 cells was
      assessed by analyzing the cells with four assays: (1) Hoechst 33258 nuclear DNA
      staining; (2) the terminal deoxynucleotidyltransferase-mediated dUTP nick end
      labeling (TUNEL) assay; (3) the nucleosomal DNA fragment ladder assay; and (4)
      the sub-G1 cell analysis. The activities of caspase-8, -9, and -3 in H1299 cells
      treated with or without THL were also measured to elucidate the possible
      mechanism underlying THL apoptosis-inducing effect. Finally, the apoptotic effect
      of THL on fifteen human cancer cell lines and normal human cells were analyzed by
      the TUNEL assay. RESULTS: THL could induce apoptosis in all human cancer cell
      lines tested but not in normal human cells. THL treatment of H1299 cancer cells
      resulted in activation of caspase-8, -9, and -3 and the inhibitors of these
      caspases could partially block THL-induced apoptosis. CONCLUSIONS: THL has been
      used by numerous patients with cancer for many years with no known adverse
      effect. Our present study showing that THL had a broad-range tumor killing
      function has provided a molecular basis underlying THL therapeutic activity.
      Furthermore, because THL had apoptotic effects only on cancer cells but not on
      normal cells, this selectivity suggests that THL could be a potential cancer
      therapeutic agent.

PMID- 15865491
TI  - Restoration of normoxia by ozone therapy may control neoplastic growth: a review
      and a working hypothesis.
AB  - In contrast to normal tissues, tumors thrive in hypoxic environments. This
      appears to be because they can metastasize and secrete angiopoietins for
      enhancing neoangiogenesis and further tumor spread. Thus, during chronic
      ischemia, normal tissues tend to die, while neoplasms tend to grow. During the
      past two decades, it has been shown in arteriopathic patients that ozonated
      autohemotherapy is therapeutically useful because it increases oxygen delivery in
      hypoxic tissues, leading to normoxia. Although several oxygenation approaches
      have been tested, none is able to restore normoxia permanently in patients with
      cancer. We postulate that a prolonged cycle of ozonated autohemotherapy may
      correct tumor hypoxia, lead to less aggressive tumor behavior, and represent a
      valid adjuvant during or after chemo- or radiotherapy. Moreover, it may re
      equilibrate the chronic oxidative stress and reduce fatigue.

PMID- 15865492
TI  - A brief but comprehensive lifestyle education program based on yoga reduces risk
      factors for cardiovascular disease and diabetes mellitus.
AB  - OBJECTIVES: The objective of the study was to study the short-term impact of a
      brief lifestyle intervention based on yoga on some of the biochemical indicators
      of risk for cardiovascular disease and diabetes mellitus. DESIGN: The variables
      of interest were measured at the beginning (day 1) and end (day 10) of the
      intervention using a pre-post design. SETTING: The study is the result of
      operational research carried out in our Integral Health Clinic (IHC). The IHC is
      an outpatient facility which conducts 8-day lifestyle modification programs based
      on yoga for prevention and management of chronic disease. A new course begins
      every alternate week of the year. SUBJECTS: The study is based on data collected
      on 98 subjects (67 male, 31 female), ages 20-74 years, who attended one of our
      programs. The subjects were a heterogeneous group of patients with hypertension,
      coronary artery disease, diabetes mellitus, and a variety of other illnesses.
      INTERVENTION: The intervention consisted of asanas (postures), pranayama
      (breathing exercises), relaxation techniques, group support, individualized
      advice, lectures and films on the philosophy of yoga and the place of yoga in
      daily life, meditation, stress management, nutrition, and knowledge about the
      illness. OUTCOME MEASURES: The outcome measures were fasting plasma glucose and
      serum lipoprotein profile. These variables were determined in fasting blood
      samples, taken on the first and last day of the course. RESULTS: Fasting plasma
      glucose, serum total cholesterol, low-density lipoprotein (LDL) cholesterol, very
      LDL cholesterol, the ratio of total cholesterol to high density lipoprotein
      (HDL) cholesterol, and total triglycerides were significantly lower, and HDL
      cholesterol significantly higher, on the last day of the course compared to the
      first day of the course. The changes were more marked in subjects with
      hyperglycemia or hypercholesterolemia. CONCLUSIONS: The observations suggest that
      a short lifestyle modification and stress management education program leads to
      favorable metabolic effects within a period of 9 days.

PMID- 15865493
TI  - The effects of meditation and visual imagery on an immune system disorder:
      dermatomyositis.
AB  - OBJECTIVE: To analyze the relationship between a patient's "spontaneous recovery"
      from dermatomyositis and her practice of transcendental meditation and visual
      imagery without confounding effects of conventional therapies. DESIGN: Study of
      time-varying relationships between (1) measures of arm strength and skin
      condition (rash and pain) and (2) mind-body interventions-controlling for
      psychologic stress-in a patient with dermatomyositis, using regression analysis
      to determine half-lives of treatments and stress. SETTING: Institutional referral
      center. INTERVENTION: Transcendental meditation and visual imagery (no drugs).
      OUTCOME MEASURES: Daily measurements of arm strength and skin condition over 294
      days. Events producing psychologic stress were also rated using a numerical
      scale. RESULTS: The patient recovered, which is a low-probability event without
      conventional therapy. Regression analysis of time dependence between measures of
      arm strength, rash, and pain and application of mind-body treatments revealed
      statistically significant relationships for both meditation (p values 0.02 to
      0.001) and visual imagery (p values 0.02 to 0.002). Stress had a significant
      negative impact on skin symptoms but not arm strength. Beneficial effects of
      meditation had half-lives of 48-59 days for skin condition and no detectable
      decay for arm strength. Benefits of visual imagery were more transient (half
      lives 4-18 days). The effects of stress had half-lives of only 1-3 days.
      CONCLUSIONS: The results demonstrate a statistically significant relationship
      between mind-body therapies and the patient's recovery from dermatomyositis,
      possibly mediated by influences on the humoral immune system. A key factor in the
      recovery was the slower decay rate of meditation and visual imagery compared to
      stress. As dermatomyositis is a humorally mediated immune microvasculopathy, the
      benefits of meditation and imagery in our patient comport with a growing body of
      evidence showing that these techniques influence immune system function.

PMID- 15865494
TI  - Beneficial effects of the Nishino breathing method on immune activity and stress
      level.
AB  - OBJECTIVES: Immunologic activity and stress level in practitioners of the Nishino
      breathing method were assayed before and after 90 minutes of an exercise class,
      in order to assess the value of the method. BACKGROUND: The Nishino Breathing
      Method was developed by Kozo Nishino, a former ballet choreographer and a master
      of martial arts, in the 1970s in an attempt to develop Ki (an internal life
      energy or a spiritual energy). Although he developed his method independently of
      the Chinese qigong practice, there are certain similarities between them, in that
      both involve visualization of internal energy flow, slow body movements, and the
      emission of life energy from one's hand. METHODS: Twenty one (21) practitioners
      were tested. Their blood was withdrawn before and after a class, and the activity
      of natural killer (NK) cells and their cell numbers were assayed. The level of
      stress was also measured using the Lorish face scale method. The heart rate was
      also monitored. RESULTS: The NK cell activity of 17 of 21 (76%) subjects
      increased after attending a class. The mean NK cell activity of the whole group
      of subjects increased after the practice (p < 0.03). The mean stress level was
      significantly reduced after the class (p < 0.001). CONCLUSIONS: These results
      demonstrated that the Nishino Breathing Method can effectively enhance the
      immunoregulatory system and reduce stress even after one class. This indicates
      that the method would help improve the health of its practitioners if they
      continue to practice it.

PMID- 15865495
TI  - Engaging in the audit of acupuncture practice.
AB  - OBJECTIVES: A pilot study was undertaken to examine the feasibility of auditing
      and developing a national database of acupuncture practice in the United Kingdom.
      METHODS: One hundred forty-five (145) practitioners, members of the British
      Acupuncture Council, were invited to participate in the study. Those who accepted
      were given training and then asked to record demographic and treatment outcomes
      data on new patients attending their practices over a 3-month period. Two
      questionnaires, the Measure Your Own Medical Outcomes Profile and the College of
      Integrated Chinese Medicine outcome questionnaire, were compared. Baseline health
      status was assessed and repeated patient feedback questionnaires employed.
      RESULTS: Of the 31 (21%) of practitioners who responded, only 9 (6%) eventually
      contributed data. A total of 69 patients participated in the study: 43 (68%) of
      the patients were female, and 46 (73%) were aged between 30 and 59. More than
      half (52%) had had their presenting problem for over 5 years and most (78%) were
      affected daily by it. Nineteen (30%) had had prior acupuncture treatment for
      their condition. The main categories of complaints reported were musculoskeletal
      and psychologic. Thirty-two (32) out of 41 (78%) patients with completed final
      outcomes data recorded moderate or major benefit in their main complaint, with no
      reports of deterioration. CONCLUSIONS: Although willing to be involved,
      practitioners found the research process time-consuming and were concerned how it
      could be balanced against the demands of a busy practice and the interests of
      patients. For a national audit study to succeed, the process would have to be
      simplified and practitioners encouraged to engage; collection of such information
      could then help to provide much-needed data on acupuncture treatment in the
      United Kingdom.

PMID- 15865496
TI  - Bioelectrographic testing of mineral samples: a comparison of techniques.
AB  - OBJECTIVES: This study was initiated to determine the suitability of differing
      techniques to record optical properties of gemstones under electromagnetic
      stimulation. Such properties are of interest due to the historical use of
      gemstones in folkloric remedies, specifically as agents for concentrating,
      focusing, or otherwise conducting energy flows in the human body. DESIGN: The
      techniques researched produce a localized corona discharge around the tested
      material. The simplest technique, Tesla coil Kirlian photography (TCKP), uses a
      Tesla coil to introduce a strong electric current, and the circuit is completed
      by a glass electrode. The corona discharge is then photographed. The other
      technique used in the study is gas discharge visualization (GDV), which uses a
      pulsed current and a digital camera integral to the coil to produce digital
      images of the corona discharge. MATERIALS: Gemstones were tested both whole and
      in powdered form. The sample gemstones were amethyst, aquamarine, garnet, golden
      citrine, pink tourmaline, and yellow topaz. Powdered gemstones were ground to a
      particle size of 2-5 microns; whole gemstones were roundcut to a diameter of 5
      mm. RESULTS: In our tests, TCKP showed divergent effects for differing types of
      gemstone. The most extreme effects were exhibited by tourmaline, both in powdered
      and whole form. In addition, TCKP appeared to indicate differing effects for
      gemstones of the identical type but mined from differing locations. The GDV
      technique showed differing data among the gemstones for the measured parameters,
      indicating that a high relative intensity did not correspond to the size of the
      corona discharge. CONCLUSIONS: While both techniques showed promise in
      distinguishing differences in corona discharge behavior in gemstone samples,
      further work is necessary to determine the significance of differences in
      geographical sources or between gemstones of similar crystalline structure. The
      techniques explored show promise in characterizing the properties of gem
      materials under electromagnetic stimulation.

PMID- 15865497
TI  - A double-blinded, placebo-controlled, randomized trial of the neuropsychologic
      efficacy of cranberry juice in a sample of cognitively intact older adults: pilot
      study findings.
AB  - OBJECTIVES: The aim of this research was to conduct the first known clinical
      trial of the short-term (i.e., 6 weeks) efficacy of cranberry juice on the
      neuropsychologic functioning of cognitively intact older adults. PARTICIPANTS:
      Fifty (50) community-dwelling, cognitively intact volunteers, > or = 60 years
      old, who reported no history of dementia or significant neurocognitive
      impairments, participated in this study. DESIGN: A 6-week, double-blind, placebo
      controlled, randomized, parallel-group, clinical trial was utilized. Participants
      were randomly assigned to receive either 32 ounces/day of a beverage containing
      27% cranberry juice per volume (n = 25) or placebo (n = 25) for 6 weeks, and
      administered a series of neuropsychologic tests at both pretreatment baseline and
      again after 6 weeks of either cranberry juice or placebo treatment to assess
      treatment-related changes. OUTCOME MEASURES: Efficacy measures consisted of
      participants' raw scores on the following standardized neuropsychologic tests:
      Selective Reminding Test, Wechsler Memory Scale-III Faces I and Faces II
      subtests, Trail Making Test (Parts A and B), Stroop Color and Word Test, and the
      Wechsler Adult Intelligence Scale- III Digit Symbol-Coding subtest. A subjective
      Follow-up Self-report Questionnaire was also administered to participants at the
      conclusion of the end-of-treatment phase assessments. RESULTS: Two-factor, mixed
      analyses of variance (ANOVA) revealed no significant group (cranberry juice and
      placebo) by trial (pretreatment baseline and end-of-treatment assessments)
      interactions across all of the neuropsychologic tests and measures utilized in
      this study when a Bonferroni corrected alpha level was used to correct for
      multiple comparisons (i.e., .05/17 group by trial comparisons = .003). Pearson
      Chi-Square analyses of the groups' self-reported changes over the 6-week
      treatment phase in their abilities to remember, thinking processes, moods, energy
      levels, and overall health on the Follow-up Self-report Questionnaire revealed no
      significant relationships. However, a nonsignificant trend (X2(1) = 2.373, p =
      0.123) was noted for participants' self-reported overall abilities to remember
      from pretreatment baseline to the end-of-treatment assessment. Specifically, more
      than twice as many participants in the cranberry group (n = 9, 37.5%) rated their
      overall abilities to remember by treatment end as "improved" as compared to
      placebo controls (n = 4, 17.4%). CONCLUSIONS: Taken together, no significant
      interactions were found between the cranberry and placebo groups and their
      pretreatment baseline and end-of-treatment phase (after 6 weeks) standardized
      neuropsychologic assessments. A nonsignificant trend was noted, however, on a
      subjective, self-report questionnaire where twice as many participants in the
      cranberry group rated their overall abilities to remember by treatment end as
      "improved" compared to placebo controls.

PMID- 15865498
TI  - Massage therapy improves the management of alcohol withdrawal syndrome.
AB  - OBJECTIVES: Massage therapy has promise as an adjunct to standard alcohol
      detoxification procedures but has not been investigated comprehensively. DESIGN:
      The study was a randomized controlled trial comparing massage therapy to a "rest"
      (control) condition in patients undergoing alcohol detoxification.
      SETTINGS/LOCATION: Hospital-based alcohol and drug detoxification clinic.
      SUBJECTS: Fifty (50) patients with alcohol dependence (41 males, 9 females).
      INTERVENTIONS: The massage intervention involved a seated back, shoulder, head,
      and neck massage. OUTCOME MEASURES: Alcohol Withdrawal Scale, respiration, pulse
      rate, and subjective patient evaluation. RESULTS: Those receiving massage
      generally showed reductions in pulse rate on 3 of the 4 days of treatment
      compared to the control group. Massage was also more effective in reducing
      Alcohol Withdrawal Scale scores in the early stages of the detoxification
      process. Respiration in the massage group was reduced toward the end of the
      detoxification admission. CONCLUSIONS: Massage shows promise as an adjunct to
      traditional medical detoxification for alcohol.

PMID- 15865499
TI  - Electroacupuncture provides a new approach to neuroprotection in rats with
      induced glaucoma.
AB  - OBJECTIVES: To investigate, using multifocal electroretinogram (mfERG), the
      effect of electroacupuncture (EA) on retinal function in rats with experimental
      glaucoma. DESIGN AND SUBJECTS: Glaucoma was induced in the right eyes of 15 adult
      female Sprague-Dawley rats by laser photocoagulation for three quarters of the
      perilimbal and episcleral vessels. The left eye of each rat was used as the
      control. The animals were divided into 3 groups: no treatment (non-EA control
      group), 2 Hz EA group, and 100 Hz EA group. EA treatment at different frequencies
      can produce different levels of analgesia and hence the effect of EA with
      different frequencies on glaucoma treatment was investigated. Both eyes of each
      rat in the EA experimental groups received 3 EA treatment sessions each week for
      4 weeks. The retinal function was measured using mfERG after 4 weeks of EA
      treatment. RESULTS: There was no significant difference in the amplitude (both N1
      trough and P1 peak) of mfERG firstorder kernel response between the treatment and
      control groups. In determining the waveform characteristics by the ratio of N1
      amplitude to P1 amplitude (N/P ratio), obvious differences were found in the N/P
      ratio between the control eyes and the glaucoma eyes in the non-EA group and the
      100 Hz EA treatment group, but similar values in the N/P ratio were observed
      between the control eyes and the glaucoma eyes in the 2 Hz EA treatment group.
      The waveform from the eyes with glaucoma was deformed in both the non-EA group
      and the 100 Hz EA group, but the waveform from the glaucomatous eye was preserved
      in the 2 Hz EA group. CONCLUSIONS: Application of EA at 2 Hz provides
      neuroprotection by preserving retinal function in rats with experimental
      glaucoma. Low frequency EA may be an alternative therapy in the treatment of
      glaucoma.

PMID- 15865500
TI  - Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum
      resin on rats with persistent inflammation.
AB  - OBJECTIVE: Ruxiang, or Gummi olibanum, an herbal medicine derived from the gum
      resin of Boswellia carterii Birdw. (BC) of the family Burseraceae, has been used
      traditionally in China to alleviate pain and reduce inflammation. The present
      study is an investigation of the effects of a BC extract on persistent
      hyperalgesia and edema in rats with peripheral inflammation. DESIGN: In this
      randomized, blinded study, the antihyperalgesic and antiedema effects of 3
      dosages of BC were compared to a vehicle control. Inflammation was induced in
      rats by injecting complete Freund's adjuvant (CFA) into one hind paw. A single
      oral dose of the BC extract was administered daily for 7 days, beginning one day
      before CFA. Hyperalgesia was assessed using a paw withdrawal latency (PWL) test
      pre-CFA and 2 hours, 5 hours, 1 day, and 5 days post-CFA. Edema was determined by
      measuring paw thickness at the same time points. Spinal Fos protein expression
      was analyzed 2 hours post-CFA. Adverse effects of the extract were monitored by
      observing the animals closely for unusual behavioral changes. RESULTS: Compared
      to control, a dosage of 0.45 g/kg BC significantly lengthened PWL and reduced paw
      edema on day 5 post-CFA. At 0.90 g/kg, BC significantly lengthened PWL at 5
      hours, 1 day, and 5 days, and reduced paw edema at 2 hours, 5 hours, 1 day, and 5
      days. This dosage also significantly suppressed spinal Fos expression in the
      medial half of laminae I-II. At 1.80 g/kg, BC significantly lengthened PWL and
      reduced paw edema at all time points. No noticeable adverse effects were observed
      in animals given the lower dosages of BC, but adverse effects in some animals
      were observed at 1.80 g/kg per day. In the acute toxicity study, the maximal
      single dose of 2.50 g/kg produced no adverse effects in the treated rats during
      the 14 days of observation. CONCLUSIONS: The data suggest that BC produces
      significant antihyperalgesia and anti-inflammation effects and that the
      antihyperalgesia may be mediated by suppressed inflammation-induced Fos
      expression in the spinal dorsal horn neurons.

PMID- 15865501
TI  - Bias control in trials of bodywork: a review of methodological issues.
AB  - OBJECTIVE: To review and summarize the methodological challenges in clinical
      trials of bodywork or handson mind-body therapies such as Feldenkrais Method,
      Alexander Technique, Trager Work, Eutony, Body Awareness Therapy, Breath Therapy,
      and Rolfing, and to discuss ways these challenges can be addressed. DESIGN:
      Review and commentary. METHODS: Search of databases PubMed and EMBASE and
      screening of bibliographies. Published clinical studies were included if they
      used individual hands-on approaches and a focus on body awareness, and were not
      based on technical devices. RESULTS: Of the 53 studies identified, 20 fulfilled
      inclusion criteria. No studies blinded subject to the treatment being given, but
      5 used an alternative treatment and blinded participants to differential
      investigator expectations of efficacy. No study used a credible placebo
      intervention. No studies reported measures of patient expectations. Patient
      expectations have been measured in studies of other modalities but not of hands
      on mind-body therapies. Options are presented for minimizing investigator and
      therapist bias and bias from differential patient expectations, and for
      maintaining some control for nonspecific treatment effects. Practical issues with
      recruitment and attrition resulting from volunteer bias are addressed.
      CONCLUSIONS: Rigorous clinical trials of hands-on complementary and alternative
      therapy interventions are scarce, needed, and feasible. Difficulties with
      blinding, placebo, and recruitment can be systematically addressed by various
      methods that minimize the respective biases. The methods suggested here may
      enhance the rigor of further explanatory trials.

PMID- 15865502
TI  - Complementary medicine and genetic medicine: polar disciplines or dynamic
      partners?
AB  - For more than a decade, a powerful movement promoting the integration of
      complementary and alternative medicine (CAM) and conventional medicine has
      evolved. Throughout the same period, there has been a monumental shift in the
      biologic sciences, and in perspectives on disease, resulting from advances in
      genetics. It is noteworthy, and perhaps not coincidental, that these "movements"
      have been occurring in parallel. The simultaneous growth of complementary
      medicine and genetic medicine may be fueled by a deep interest in the development
      of "personalized" medicine. There is a prevailing view that the metaphysical
      visions of these two fields are in conflict. To advance discussion of this
      question, we describe what we believe are the common philosophies and goals of
      these apparently disparate fields, and why it would be advantageous for them to
      work together in the service of the public's health.

PMID- 15865503
TI  - Classification of human population based on HLA gene polymorphism and the concept
      of Prakriti in Ayurveda.
AB  - BACKGROUND: Correlating phenotypes with genotypes remains the major postgenomic
      challenge. Attempts to correlate phenotype characteristics associated with
      ethnicity, geographical divisions, or diseases to genotypes have had limited
      success. This means that current approaches for identifying phenotypes associated
      with haplotypes may be inadequate. OBJECTIVES: We hypothesize that a human
      phenome based on Ayurveda could provide an appropriate approach. Specifically,
      there could be a genetic basis for the three major constitutions (Prakriti)
      described in Ayurveda. The Prakriti classification is based on differences in
      physical, physiological, and psychologics characteristics and is independent of
      racial, ethnic, or geographical considerations. It may provide an appropriate
      means of classifying phenotypes to be considered collectively for genotyping.
      DESIGN: As a pilot study to test the hypothesis, we evaluated 76 subjects both
      for their Prakriti and human leucocyte antigen (HLA) DRB1 types. The genomic DNA
      was extracted using a standard protocol. Subsequently, HLA DRB1 typing was done
      by low-resolution polymerase chain reaction sequence specific primers and
      oligonucleotide probes. RESULTS: We observed a reasonable correlation between HLA
      type and Prakriti type. The complete absence of the HLA DRB1*02 allele in the
      Vata type and of HLA DRB1*13 in the Kapha type are significant, with X2 = 4.715
      and p < 0.05. HLA DRB1*10 had higher allele frequency in the Kapha type than in
      the Pitta and Vata types. CONCLUSION: Ayurveda classifies the whole human
      population in three major constitutions as Vata, Pitta, Kapha and their possible
      combinations. Their homologous relation to human genetic structure needs to be
      studied for validation. If validated, our hypothesis would have far reaching
      implications for pharmacogenomics, modern genetics, human health, and Ayurveda.

PMID- 15865504
TI  - Understanding premenstrual syndrome from a Chinese medicine perspective.
AB  - Premenstrual syndrome (PMS) is a common disorder of some women during their
      reproductive years, characterized by a range of cyclical physical and/or mood
      symptoms experienced during the last few days of each menstrual cycle. Several
      treatment approaches have been applied, but have shown limited success, as the
      exact cause and pathophysiology of PMS is still not fully identified. In this
      paper, the etiology and pathogenesis of PMS is compared from both a Traditional
      Chinese Medicine (TCM) perspective and the Western biomedicine paradigm. TCM has
      used herbal medicines to treat the symptoms of the premenstrual and menstrual
      phases for centuries. To date, very few studies on the application of TCM to PMS
      have applied rigorous research methods. We examine the case of PMS from each
      paradigm: The biomedical view and that of TCM. Similarities and differences are
      identified and explored, and possible treatment approaches are considered and
      discussed in the light of these two models.

PMID- 15865505
TI  - Major ozonated autohemotherapy in chronic limb ischemia with ulcerations.
AB  - This paper reports the beneficial effects of ozone autohemotherapy (OHT) in 2
      patients afflicted with painful, intractable leg ulcers. One patient had diabetes
      mellitus type II (DM), the other had vasculitis. Both patients had seen multiple
      specialists, including a dermatologist, an internist, and a vascular surgeon, but
      their clinical course continued to worsen. When the pain became intolerable, the
      patients came to our pain clinic. Chemical lumbar sympathectomy as well as
      epidural blockade with bupivacaine and morphine were moderately effective in
      reducing their pain but had no effect on the ulcers. Only after OHT treatments
      were performed for several months was satisfactory healing observed.

PMID- 15865506
TI  - The effectiveness of grapefruit (Citrus paradisi) seeds in treating urinary tract
      infections.
AB  - Three middle-aged males and one female were diagnosed as having urinary tract
      infections (UTIs) between 2001 and 2003 in the Wesley Guild Hospital, Ilesa, a
      unit of Obafemi Awolowo University Teaching Hospitals Complex, Ile Ife, Osun
      State, Nigeria. Of the 4 patients, only the female was asymptomatic. The 3 males
      had Pseudomonas aeruginosa, Klebsiella species, and Staphylococcus aureus,
      respectively, in their urine samples, while the female had Escherichia coli. All
      4 patients were treated with grapefruit seeds (Citrus paradisi) orally for 2
      weeks and they all responded satisfactorily to the treatment except the man with
      P. aeruginosa isolate. However, the initial profuse growth of Pseudomonas isolate
      in the patient that was resistant to gentamicin, tarivid, and augmentin later
      subsided to mild growth with reversal of the antibiotic resistance pattern after
      2 weeks' treatment with grapefruit seeds. These preliminary data thus suggest an
      antibacterial characteristic of dried or fresh grapefruit seeds (C. paradisi)
      when taken at a dosage of 5 to 6 seeds every 8 hours, that is comparable to that
      of proven antibacterial drugs.

PMID- 15865507
TI  - Integration of complementary and alternative medicine in a major pediatric
      teaching hospital: an initial overview.
AB  - OBJECTIVE: To describe the establishment of a multidisciplinary team of
      complementary and alternative medicine (CAM) providers and educators in an urban
      pediatric hospital and affiliated medical school. BACKGROUND: Pediatric CAM use
      is increasing. Physicians are interested in CAM-related education but few
      programs had been developed in pediatrics. In 1998, Children's Hospital Boston
      established the Center for Holistic Pediatric Education and Research (CHPER), a
      CAM multidisciplinary team providing clinical services, education, and research.
      METHOD: A retrospective review describing data from patient consultation notes,
      CAM lectures, clinical practice guidelines, curriculum materials, team meeting
      minutes, and team member manuscripts and publications. RESULTS: Over 5.5 years,
      CHPER staff provided over 2100 consults: acupuncture, massage, holistic
      pediatrician, relaxation therapies, biofeedback, hypnosis, and bio-pharmaceutics.
      Acupuncture and massage therapies were incorporated into a Clinical Practice
      Guideline. Formal education was delivered through didactic sessions, workshops,
      self-learning modules, clinical observation, and clinical practice. CHPER faculty
      published 1 book and 64 articles on CAM-related topics. CONCLUSION: An
      interdisciplinary team of CAM clinicians and educators can be integrated into an
      urban pediatric teaching hospital to provide CAM medical education and clinical
      services.

PMID- 15865510
TI  - A pioneer in laparoscopy and pelviscopy: Kurt Semm (1927-2003).

PMID- 15865511
TI  - Laparoscopic adrenal surgery: new frontiers.
AB  - After about 10 years of experience, laparoscopic adrenalectomy has become the
      gold standard for the treatment of adrenal lesions. Here, we describe the
      presenting features, imaging methods, and current surgical approaches to diseases
      of the adrenal gland. There is general agreement on the suitability of the
      laparoscopic approach for benign adrenal lesions, but controversy exists about
      using laparoscopy for suspected adrenal malignancy, metastasis, and partial
      adrenalectomy. This article reviews the literature on laparoscopic adrenalectomy.
      In particular, we focus our attention on the new surgical approaches to the
      gland. We evaluate the indications, operative techniques, and tools for partial
      adrenalectomy, and we discuss new surgical strategies such as cryosurgery and
      radiofrequency ablation.

PMID- 15865512
TI  - Defining the learning curve for percutaneous nephrolithotomy.
AB  - PURPOSE: To define the learning curve for percutaneous nephrolithotomy (PCNL)
      using three potential surrogate markers of surgical expertise. MATERIALS AND
      METHODS: The learning curve of an endourologist with no previous experience at
      performing solo PCNL was studied. Three putative parameters of expertise were
      reviewed, namely, operating time, fluoroscopic screening time, and radiation
      dose. Operations were analyzed in cohorts of 15 to determine when a plateau was
      reached for all three variables. Comparison was then made with the results of a
      surgeon who had performed more than 1600 PCNLs. Stone type and stone clearance
      rate were also noted. RESULTS: The mean operating time of the novice surgeon fell
      to a plateau of 92 minutes after 60 cases, but screening time and radiation dose
      did not plateau until case 115, when values of 231 seconds and 406 cGy/cm2 were
      recorded, respectively. The senior surgeon had a mean operating time of 98
      minutes and screening parameters equivalent to those of the novice surgeon after
      115 cases. The complexity of the stones tackled grew with increasing experience,
      although stone-free rates remained constant. CONCLUSIONS: This study of the
      learning curve of a single surgeon suggests that competence at performing PCNL is
      reached after 60 cases and excellence after 115. Radiation parameters are a
      valuable tool in the assessment of operative competence.

PMID- 15865513
TI  - Gender Differences among Hispanics and Caucasians in symptomatic presentation of
      kidney and ureteral stones.
AB  - PURPOSE: We determined gender differences in the symptomatic presentation of
      kidney and ureteral stones among the Hispanic population and compared it with
      presentation in the Caucasian population. PATIENTS AND METHODS: A retrospective
      chart review was performed on 443 patients seen in our Emergency Department or
      Urgent Care Center for symptomatic kidney or ureteral stones over a 5-year
      period. Demographic information was obtained, including sex, race, age, location
      of stone, stone size, and type of urologic intervention. Of the 443 patients, 263
      (59%) were Hispanic, and 180 (41%) were Caucasian. RESULTS: The male-to-female
      ratio of the symptomatic patients with kidney stones was 1.48 for both Hispanic
      and Caucasian patients. The male-to-female ratio for ureteral stones was 1.06 and
      2.48 for the Hispanic and Caucasian patients, respectively (P < 0.05). The rate
      of urologic intervention was similar among Caucasian males and females and
      Hispanic females (approximately 33%) but significantly lower among Hispanic males
      (18%). CONCLUSIONS: The relative symptomatic presentation of ureteral stones of
      men and women among the Hispanic population is nearly 1:1, whereas the ratio in
      Caucasian men and women approaches the previously reported 2.5:1. No significant
      racial or sex differences were noted in the symptomatic presentation of kidney
      stones. In comparison with Hispanic men, Hispanic women undergo significantly
      more urologic interventions for symptomatic urolithiasis.

PMID- 15865514
TI  - Laparoscopic ureteral resection and anastomosis for management of low-grade
      transitional-cell carcinoma.
AB  - Laparoscopic segmental ureterectomy and ureteroureterostomy was carried out in a
      patient with a low-grade ureteral tumor. To our knowledge, this approach is the
      first application of laparoscopic segmental ureterectomy for proximal ureteral
      tumor.

PMID- 15865515
TI  - Laparoscopic excision of prostatic hydatid cyst: case report and review of
      literature.
AB  - It is rare for hydatid disease to be encountered primarily in the urogenital
      system or retroperitoneum. Moreover, prostatic involvement is extremely rare. We
      present a case report of prostatic hydatid cyst that was treated with
      laparoscopic excision. We reviewed diagnosis and management of hydatid disease of
      the urogenital tract.

PMID- 15865516
TI  - Endoscopic cross-trigonal ureteral reimplantation under carbon dioxide bladder
      insufflation: a novel technique.
AB  - PURPOSE: To report on a novel technique of endoscopic intravesical ureteral
      mobilization and cross-trigonal ureteral reimplantation under carbon dioxide
      insufflation of the bladder (pneumovesicum) for correcting primary vesicoureteral
      reflux (VUR) in infants and children. PATIENTS AND METHODS: Ten boys and six
      girls with dilating primary VUR (7 bilateral; 23 refluxing ureters) associated
      with recurrent urinary-tract infections and multiple pyelonephritic renal scars
      underwent endoscopic Cohen's cross-trigonal ureteral reimplantation with CO(2)
      pneumovesicum. Their ages ranged from 10 months to 13 years (mean 4.1 years). The
      endoscopic procedure was preceded by distention of the bladder with saline and
      insertion of a 5-mm Step port over the bladder dome under cystoscopic guidance.
      The bladder was then drained and insufflated with CO(2) to 10 to 12 mm Hg
      pressure with a suction catheter inserted per urethra to occlude the internal
      urethral meatus. A 5-mm 30 degrees endoscope was used to provide intravesical
      vision. Two more 3- to 5-mm working ports were inserted on the lateral bladder
      wall on either side. Endoscopic intravesical mobilization of the ureter,
      dissection of a submucosal tunnel, and a Cohen's type of crosstrigonal ureteral
      reimplantation using interrupted 5-0 monofilament sutures was then performed
      under videoscopic guidance. Bladder drainage by a urethral catheter was
      maintained for 24 hours postoperatively. RESULTS: Endoscopic cross-trigonal
      ureteral reimplantation under CO(2) pneumovesicum was successfully performed in
      all except one patient, who had displacement of a port into the extravesical
      space after completion of the ureteral reimplantation necessitating a small
      vesicotomy for closure of the mucosal defect. The mean operating time was 136
      minutes (range 80-230 minutes), being 112 minutes for unilateral cases and 178
      minutes for bilateral cases. Two boys developed mild suprapubic and scrotal
      emphysema postoperatively that subsided spontaneously. All other patients
      recovered uneventfully and remained well. Follow-up cystograms showed complete
      resolution of VUR in all except one unit that had persistent grade I reflux, thus
      giving a success rate of 96%. CONCLUSIONS: This early experience illustrates that
      endoscopic intravesical ureteral mobilization and crosstrigonal ureteral
      reimplantation can be performed safely and effectively with routine laparoscopic
      surgical techniques and instruments under CO(2) insufflation of the bladder,
      achieving a high success rate in reflux resolution that is equivalent to that
      obtained with the open technique but with minimal invasiveness and much faster
      recovery. The longer-term outcome and potential physiological effects of CO(2)
      pneumovesicum on the bladder and upper-tract function will need to be evaluated
      further.

PMID- 15865517
TI  - Technical considerations for laparoscopic right renal surgery in presence of
      Riedel's lobe of the liver.
AB  - Riedel's lobe of the liver is an anatomic variant, described as a caudal
      extension of the right lobe of the liver, that presents a challenge in
      laparoscopic right renal surgery. A 52-year-old woman with a Riedel's lobe of the
      liver and a large right renal mass underwent laparoscopic right radical
      nephrectomy. Transperitoneal access with the Veress needle through a right
      lateral port was initially unsuccessful. After a supraumbilical approach,
      pneumoperitoneum was eventually achieved. The right lateral liver attachments
      were freed, and the lobe was retracted medially to expose the right kidney and
      its hilum. The surgery was then performed successfully. Riedel's lobe presents
      two special technical concerns: intraperitoneal access and hilar exposure. For
      access, an initial supraumbilical approach, or possibly an open approach,
      decreases the risk of liver injury. For renal and hilar exposure, the right
      lateral liver attachments can be taken down so that the hepatic lobe can be
      retracted medially instead of in the conventional cephalad direction.
      Retroperitoneal access, if feasible, may also circumvent these problems. Surgery
      can then be performed safely and effectively.

PMID- 15865518
TI  - Laparoscopic partial cystectomy for schwannoma of urinary bladder: case report.
AB  - Primary schwannomas of the urinary bladder are extremely rare. They arise from
      Schwann's cells in nerve sheaths and are often associated with von
      Recklinghausen's disease. In these cases, open partial cystectomy has been the
      choice of treatment. We performed laparoscopic partial cystectomy in a 35-year
      old man who showed a 3.5-cm solid bladder mass on pelvic CT. The lesion was found
      to be a primary schwannoma of the urinary bladder without evidence of von
      Recklinghausen disease.

PMID- 15865519
TI  - Bursting strength with various methods of renal artery ligation and potential
      mechanisms of failure.
AB  - BACKGROUND AND PURPOSE: Vascular control is crucial during laparoscopic ligation
      of the renal vessels. Intracorporeal suture ligation has been replaced by easier
      methods, such as specialized clip appliers and automatic stapling devices;
      nevertheless, the optimal application and margin of safety of such devices have
      yet to be determined. We sought to address this question by measuring the
      bursting strength of arteries ligated with several standard devices. MATERIALS
      AND METHODS: One end of an adult porcine artery (3-7-mm diameter) was occluded
      with a titanium clip, self-locking polymer clip, or laparoscopic linear cutting
      stapler. Comparisons were made with one or two clips and with different distal
      cuff lengths (i.e., flush or 2 mm). The open end was secured to a pulsatile
      infusion pump. Leak/failure pressures were measured using a digital barometer.
      RESULTS: The mean bursting pressures for the clips were above physiologic
      arterial pressures (1220-1500 mm Hg). However, the vessels closed with the
      stapler leaked at a lower mean pressure (262 mm Hg). Failure of titanium or self
      locking polymer clips was the result of vessel retraction into and behind the
      clip, while staple- line leakage occurred between individual staples. Bursting
      pressures with the titanium and self-locking polymer clips was unaffected by the
      number of clips or length of vascular cuff. CONCLUSIONS: All tested methods of
      vascular control performed well at physiologic pressures, suggesting that safety
      is not increased with traditional maneuvers such as additional clips or longer
      cuff length.

PMID- 15865520
TI  - What happens to hemostatic agents in contact with urine? An in vitro study.
AB  - BACKGROUND AND PURPOSE: As the indications for topical hemostatic agents increase
      in urology, the question arises: what happens to these agents when they enter the
      urinary collecting system? To answer this question, we performed a series of in
      vitro experiments mixing three hemostatic agents with normal and sanguineous
      urine. MATERIALS AND METHODS: Four commercially available topical hemostatic
      products: oxidized regenerated cellulose (Surgicel; Ethicon, Somerville, NJ),
      fibrin sealant (Tisseel VH Kit; Baxter Health Care Corporation, Irvine, CA),
      gelatin matrix hemostatic sealant (FloSeal; Baxter Health Care), and polyethylene
      glycol (CoSeal; Cohesion Technologies, Palo Alto, CA) were studied. Human urine
      (10 mL) was added to samples of each substance; this was done in triplicate. The
      12 sample tubes were then capped and placed on a tube shaker at slow speed and 37
      degrees C. Observations regarding consistency of the material were made at 6, 12,
      24, 48, 72, 96, and 120 hours (5 days). Gelatin matrix hemostatic sealant was
      further tested in urine with various amounts of blood or blood clot; observations
      were again recorded out to 5 days. RESULTS: Surgicel maintained its solid form
      when it initially came in contact with urine, but over a period of 5 days, it
      transformed into a mucoid substance with visible free-floating fibers. It did not
      dissolve completely in urine within 5 days. Gelatin matrix was immediately
      transformed by urine into a fine colloidal suspension that did not change over
      the 5 days of the study. Fibrin glue, after mixing of the two components
      (fibrinogen and thrombin) directly in the urine, and polyethylene glycol
      immediately formed a solid clot at the bottom of the test tube on contact with
      the urine. When the mixture of fibrin sealant was allowed to form for 15 minutes
      and then added to urine, it again maintained a solid form. After 72 hours, the
      fibrin glue became a semisolid gelatinous plug. On analysis at 5 days, the fibrin
      sealant clot had transformed into a cohesive mucoid gel, and the polyethylene
      glycol clot had not changed. The gelatin matrix hemostatic sealant, when in
      contact with blood or blood clot, appeared to either become part of a clot or to
      remain in a colloidal suspension. At 5 days, all clots had dissolved to fine
      particulate suspensions, and the gelatin matrix appeared as a fine suspension.
      CONCLUSION: Fibrin glue and oxidized regenerated cellulose maintain a solid form
      when initially placed in direct contact with urine and then assume a semisolid
      gelatinous state, which is still present at 5 days. Polyethylene glycol forms a
      solid clot initially and does not change after 5 days. Only hemostatic gelatin
      matrix remained as a fine particulate suspension in both normal and sanguineous
      urine. The implications of these findings with regard to sealing the renal
      parenchyma or small violations of the collecting system after percutaneous or
      laparoscopic surgery await in-vivo testing.

PMID- 15865521
TI  - Prospective longitudinal comparative study of health-related quality of life in
      patients undergoing invasive treatments for localized prostate cancer.
AB  - BACKGROUND AND PURPOSE: Health-related quality of life (QoL) concerns are
      important for patients selecting treatment options for clinically localized
      prostate cancer and are critical in evaluating outcomes. We report pretreatment
      and post-treatment general and disease-specific QoL for the following invasive
      interventions: open radical prostatectomy (ORP), laparoscopic radical
      prostatectomy (LRP), and palladium-103 ((103)Pd) brachytherapy. PATIENTS AND
      METHODS: We performed a prospective longitudinal survey of 452 patients with
      newly diagnosed prostate cancer treated at a single medical center between 2001
      and 2003. An Institutional Review Board-approved questionnaire comprised of
      validated QoL instruments was sent to patients scheduled to undergo ORP (N =
      186), LRP (N = 116), or brachytherapy (N = 150). The same questionnaire was sent
      out 1, 3, 6, 9, and 12 months after therapy. Comparisons were made between the
      groups to determine if the choice of therapy resulted in differences in QoL.
      RESULTS: General QoL scores were minimally affected by the choices; however, the
      disease-specific domains of bowel, urinary, and sexual function were adversely
      affected by all modalities. The ORP and LRP groups were similar among disease
      specific domains and received lower post-treatment urinary and sexual scores than
      the (103)Pd patients. At 12 months, 38% of ORP and 46% of LRP patients had
      returned to baseline urinary function compared with 75% of (103)Pd patients. At
      12 months, 63% of (103)Pd patients had returned to baseline sexual function
      compared with 19% of both the LRP and ORP patients. CONCLUSIONS: Invasive
      treatments for localized prostate cancer have little impact on general QoL but
      significantly affect disease-specific domains. Both ORP and LRP have a greater
      initial negative impact on urinary and sexual function than (103)Pd. The
      differences among the treatments with regard to QoL provide information to
      patients faced with choosing a treatment.

PMID- 15865522
TI  - Complete daVinci versus laparoscopic pyeloplasty: cost analysis.
AB  - BACKGROUND AND PURPOSE: Computer-assisted pyeloplasty with the daVinci system is
      an emerging technique to treat ureteropelvic junction (UPJ) obstruction. A
      relative cost analysis was performed assessing this technology in comparison with
      purely laparoscopic pyeloplasty. PATIENTS AND METHODS: Eight patients underwent
      computer-assisted (daVinci) dismembered pyeloplasty (CP) via a transperitoneal
      four-port approach. They were compared with 13 patients who underwent purely
      laparoscopic pyeloplasty (LP). All patients had a primary UPJ obstruction and
      were matched for age, sex, and body mass index. The cost of equipment and capital
      depreciation for both procedures, as well as assessment of room set-up time,
      takedown time, and personnel were analyzed. Surgeons and nursing staff for both
      groups were experienced in both laparoscopy and daVinci procedures. One- and two
      way financial analysis was performed to assess relative costs. RESULTS: The mean
      set-up and takedown time was 71 minutes for CP and 49 minutes for LP. The mean
      length of stay was 2.3 days for CP and 2.5 days for LP. The mean operating room
      (OR) times for CP and LP were 176 and 210 minutes, respectively. There were no
      complications in either group. One-way cost analysis with an economic model
      showed that LP is more cost effective than CP at our hospital if LP OR time is
      <338 minutes. With adjustment to a volume of 500 daVinci cases/year, CP is still
      not as cost effective as LP. Two-way sensitivity analysis shows that in-room time
      must still be <130 minutes and yearly cases must be >500 to obtain cost
      equivalence for CP. CONCLUSIONS: Perioperative parameters for CP are encouraging.
      However, the costs are a clear disadvantage. In our hospital, it is more cost
      effective to teach and perform LP than to perform CP.

PMID- 15865523
TI  - Bipolar versus monopolar transurethral resection of prostate: randomized
      controlled study.
AB  - BACKGROUND AND PURPOSE: Transurethral resection of prostate (TURP) using bipolar
      electrocautery and physiologic saline is a new technical advancement in the field
      of surgical management of benign prostatic hyperplasia. The purpose of this study
      was to assess the efficacy and safety of this new technique and to compare the
      results with those of conventional monopolar TURP. PATIENTS AND METHODS: This
      study included 60 patients who were randomized 1:1 to bipolar (group 1) or
      monopolar (group 2) TURP. Bipolar TURP was performed with the Vista CTR
      resectoscope and generator (ACMI Corp.). Preoperatively, patients were assessed
      by symptom score, uroflow, and transrectal sonography, and the two groups were
      comparable with regard to these measures and age. The preoperative and
      postoperative parameters studied included resection time, amount of tissue
      resected, irrigant amount, blood loss, fluid absorption, and change in serum
      sodium and hemoglobin. Postoperatively, patients were assessed for symptoms,
      symptom score, and uroflow rate at 1 and 3 months. RESULTS: There was no
      difference in resected tissue amount, irrigant amount, fluid absorption, duration
      and amount of postoperative irrigation, or fall in hemoglobin. The mean resection
      rate was 0.61 g/min in group 1 and 0.74 g/min in group 2. Serum Na dropped by 4.6
      Eq/L in group 2, whereas it fell only 1.2 mEq/L in group 1 (P < 0.001).
      Improvement in symptom and QoL scores and Q(max) were similar in the two groups.
      Postoperative dysuria was less common with bipolar resection. CONCLUSION: Bipolar
      resection of the prostate is as effective as monopolar TURP. Moreover, it does
      not lead to any change in serum Na and causes less postoperative dysuria.

PMID- 15865524
TI  - Accuracy of three-dimensional CT angiography for preoperative vascular evaluation
      of laparoscopic living renal donors.
AB  - PURPOSE: A retrospective review of preoperative three-dimensional (3D) CT and the
      operative findings during laparoscopic donor nephrectomy. PATIENTS AND METHODS:
      Fifty-four consecutive patients underwent laparoscopic donor nephrectomy. Of
      these patients, 51 had preoperative 3D reconstructed CT scans. Each radiologic
      report was compared with the operative report. RESULTS: The 3D CT correctly
      identified the arteries in 98% of the patients and the veins in 96%. CONCLUSIONS:
      Preoperative CT angiography can accurately identify the renal vasculature.

PMID- 15865525
TI  - Semirigid ureteroscopy of the proximal ureter can be aided by external lower
      abdominal pressure.
AB  - BACKGROUND AND PURPOSE: Smaller semirigid ureteroscopes with large working
      channels and excellent optics are widely available. Ureteroscopic treatment of
      upper-ureteral stones has become increasingly popular, although flexible
      ureteroscopy is more frequently the method of choice. Access to the upper ureter
      with a semirigid ureteroscope (SR-URS) can be challenging and hazardous,
      especially when negotiating the iliac vessels. We sought to determine whether
      lower-abdominal pressure (LAP) facilitated SR-URS access to the upper ureter for
      safe laser lithotripsy. PATIENTS AND METHODS: Thirty-two consecutive patients who
      underwent ureteroscopic management of upper- ureteral stones were evaluated.
      Twenty-four (75%) were male; seventeen (53%) had a right-sided stone. The mean
      largest stone diameter was 10.2 +/- 4.6 mm. These 32 patients were compared with
      a matched cohort of patients who underwent SR-URS procedures without the use of
      LAP. RESULTS: Access to the upper ureter was possible in 30 patients (94%). The
      LAP was helpful in 18 patients (56%): it facilitated passage of the SR-URS in 16
      patients (50%) and laser fiber placement in 11 cases (34%). Access to the upper
      ureter was possible in all women. The mean operative time was 54 minutes in the
      LAP group and 75 minutes in the matched cohort without LAP (P = 0.026). There
      were no significant deformities of the SR-URS and no complications. CONCLUSIONS:
      Contrary to popular practice, the upper ureter can be accessed safely and
      efficiently with a 7.5F SR-URS in nearly all patients. Lower-abdominal pressure
      can be helpful to negotiate passage of the endoscope over the iliac vessels or to
      place the laser fiber on stones.

PMID- 15865526
TI  - Using and choosing a nephrostomy tube after percutaneous nephrolithotomy for
      large or complex stone disease: a treatment strategy.
AB  - BACKGROUND AND PURPOSE: Percutaneous nephrolithotomy (PCNL) is a well-accepted
      technique for removal of large or complex renal calculi. However, little
      attention has been paid to strategies for nephrostomy tube (NT) selection. We
      reviewed the reasons for selecting three types of NT after PCNL for large or
      complex stone disease. PATIENTS AND METHODS: A series of 106 consecutive renal
      units undergoing PCNL for stone burdens >2 cm by a single surgeon (JEL) were
      reviewed. Noncontrast CT (NCCT) was carried out on postoperative day 1, and
      secondary procedures were performed if fragments remained. The NTs studied were
      8.5F and 10F Cope loops (CP), 20F reentry Malecot catheters (REM), and 20F circle
      loops (CL). Patient demographics, access site and number, complications, and
      stone type were examined. "Stone free" was defined as a negative NCCT or negative
      second-look PCNL. RESULTS: A total of 134 accesses were created in 106 renal
      units: 35 upper, 7 mid, and 92 lower; however, only 111 NTs were placed: 85 CP
      (76.6%), 19 REM (17.1%), and 7 CL (6.3%). Sixteen accesses were performed
      tubeless; all but two were in the upper pole. All 16 of these renal units had a
      concomitant NT placed in the lower pole. Multiple sites were accessed in 21
      patients; 7 of these patients had CL placed. Five of ten patients with spinal
      cord injury had REM/CL placed. Nineteen REM were placed: 10 for drainage of
      infection, and 9 for difficult anatomy. All renal units were rendered stone free:
      31.1% with a single procedure and 95.6% with one or two procedures. There were no
      difficulties with drainage or access for secondary PCNL regardless of the NT
      employed. Complications included two hydrothoraces, one arteriovenous fistula,
      and one ureteral perforation. Three of four renal units in patients requiring
      transfusions underwent bilateral PCNL, and at least one renal unit required
      multiple accesses. Of kidneys with infection stones, 57.1% required REM or CL;
      only 12.0% of nonstruvite stones necessitated REM or CL. CONCLUSIONS: All
      patients having PCNL done for complex stone disease should have an NT placed;
      however, small (8.5F-10F) CP suffice in most cases and can provide greater
      patient comfort. To minimize pleural morbidity, tubeless upper-pole access should
      be considered if the kidney is judged to be stone free at the conclusion of PCNL.
      Circle loops are useful when multiple accesses are necessary, whereas REM are
      appropriate if access is difficult, gross residual stone remains, or pain is not
      an issue (i.e., spinal-cord injury).

PMID- 15865527
TI  - Role of laparoscopy in management of renal stones: single-center experience and
      review of literature.
AB  - BACKGROUND AND PURPOSE: Laparoscopy can be an alternative modality in the
      management of renal stones. We present our experience with laparoscopic renal
      stone surgery. PATIENTS AND METHODS: Eighteen patients (4 males, 14 females) with
      mean age of 51 years (range 18-86 years) underwent 19 laparoscopic procedures.
      The mean stone number and size, excluding five patients who had
      nephrectomy/heminephrectomy, were 1.9 (range 1-5) and 1.3 cm (range 0.5-4.5 cm),
      respectively. Three patients with ureteropelvic junction obstruction underwent
      pyeloplasty and concomitant pyelolithotomy. Three patients with upper-pole
      caliceal-diverticular stones had nephrolithotomy and fulguration of the
      diverticular mucosa. Three patients with stones and hydrocalix with scarred
      cortex had partial nephrectomy, two under cold and one under warm ischemia. Five
      patients, including one with a horseshoe kidney (who had one procedure on each
      kidney), had pyelolithotomy as an alternative to percutaneous nephrolithotomy.
      Patients with stones in a nonfunctioning kidney underwent nephrectomy (three
      patients) or heminephrectomy (one patient). RESULTS: All procedures were
      completed laparoscopically. The operative time was variable depending on the
      complexity of the procedures, from 115 minutes for Fengerplasty to 315 minutes
      for partial nephrectomy under cold ischemia (mean 178 minutes). The estimated
      blood loss was 53.2 mL (range 20-120 ml), and none of the patients received a
      blood transfusion. Complete stone clearance was achieved in 93% of the
      procedures. The mean hospital stay was 10.5 days (range 5-35 days). Three
      patients needed temporary pigtail-catheter drainage for obstruction after
      pyelolithotomy. One patient with a solitary kidney and infected staghorn calculus
      had prolonged urinary leak, which stopped with conservative management. One
      nephrectomy for nephrocutaneous fistula was complicated by a late colonic
      perforation necessitating colostomy. CONCLUSION: Laparoscopic surgery is
      effective for complex renal stones and allows for adjunctive procedures. It can
      also be an alternative to percutaneous nephrolithotomy. It complements other
      minimally invasive procedures, and a need for open stone surgery should be rare
      in the future.

PMID- 15865528
TI  - Initial impact of a dedicated postgraduate laparoscopic mini-residency on
      clinical practice patterns.
AB  - BACKGROUND AND PURPOSE: Laparoscopic surgical techniques are difficult to master,
      especially for surgeons who did not receive this type of training during their
      residencies. We have established a 5-day mentor-preceptor- proctor-guided
      postgraduate "mini-residency" (M-R) experience in minimally invasive surgery. The
      initial results from the first 16 participants in the laparoscopic M-R modules
      are presented. PARTICIPANTS AND METHODS: On the first and the last day of the M
      R, all participants underwent surgical skills testing using an open-surgery,
      standard laparoscopic, and robot-assisted laparoscopic format. A written
      examination was also administered on the last day. The influence of M-R on the
      participants' practice pattern was then assessed by a follow-up questionnaire
      survey 1 to 7 months after their attendance. RESULTS: Data from the first 16
      participants were analyzed. Of note, the score was significantly improved for
      only one of the four tested laparoscopic skills (i.e., threading a suture through
      loops). Nonetheless, on the follow-up survey, of the 15 respondents, two
      laparoscopically naive participants had performed laparoscopic nephrectomy, and
      of the eight participants who had prior renal-ablative laparoscopic experience,
      four had performed advanced reconstructive laparoscopic cases. CONCLUSIONS: A 5
      day dedicated postgraduate M-R in laparoscopy appears to be helpful for
      urologists wishing to incorporate this surgical approach into their practices.
      The "take rate" among participants is initially at the 40% level, similar to what
      has been previously reported after a 1 to 2-day hands-on didactic laparoscopy
      course.

PMID- 15865529
TI  - Current practice patterns in urologic management of upper-tract transitional-cell
      carcinoma.
AB  - PURPOSE: To determine the current practice patterns in the management of upper
      tract transitional-cell carcinoma (TCC) among a large group of urologists.
      MATERIALS AND METHODS: A survey was sent to 220 practicing members of the Society
      of Urologic Oncology (SUO) and the Endourological Society (ES) and members of the
      American Urological Association who did not belong to either society. The survey
      consisted of 16 focused questions pertaining to the surveillance and management
      of upper-tract TCC. The responses were used to create a database, which was then
      analyzed to determine practice trends. RESULTS: Eighty-four of the urologists
      responded, for a response rate of 38%. Fourteen responses were excluded because
      of multiple answers to a given question, so 70 were included in the final
      analysis. Eighty percent of the respondents were in academic practice. A CT
      urogram was the favored initial procedure for diagnosis of upper-tract TCC and an
      intravenous urogram was the next commonest choice (53% and 40%, respectively).
      Ureterorenoscopy was the surveillance tool of choice (70%) after conservative
      treatment of upper- tract TCC. Laparoscopic nephroureterectomy was the preferred
      procedure (73%) for a high-grade, large renal-pelvic TCC. Twenty-one percent of
      the endourologists recommended ureteroscopic ablation for a high-grade, large
      distal ureteral tumor. This was in sharp contrast to 77% of the respondents who
      favored a distal ureterectomy for the same clinical scenario. CONCLUSIONS: This
      study confirms that most urologists treating upper-tract TCC follow the
      principles reported in the published literature regarding the management of these
      patients. Further, most urologists, regardless of society affiliations or years
      in practice, favor minimally invasive techniques for the management of upper
      tract TCC. This information may be useful in formulating clear guidelines for the
      management of this disease.

PMID- 15865530
TI  - Can video games be used to predict or improve laparoscopic skills?
AB  - BACKGROUND AND PURPOSE: Performance of laparoscopic surgery requires adequate
      hand-eye coordination. Video games are an effective way to judge one's hand-eye
      coordination, and practicing these games may improve one's skills. Our goal was
      to see if there is a correlation between skill in video games and skill in
      laparoscopy. Also, we hoped to demonstrate that practicing video games can
      improve one's laparoscopic skills. SUBJECTS AND METHODS: Eleven medical students
      (nine male, two female) volunteered to participate. On day 1, each student played
      three commercially available video games (Top Spin, XSN Sports; Project Gotham
      Racing 2, Bizarre Creations; and Amped 2, XSN Sports) for 30 minutes on an X-box
      (Microsoft, Seattle, WA) and was judged both objectively and subjectively. Next,
      the students performed four laparoscopic tasks (object transfer, tracing a figure
      of-eight, suture placement, and knot-tying) in a swine model and were assessed
      for time to complete the task, number of errors committed, and hand-eye
      coordination. The students were then randomized to control (group A) or
      "training" (i.e., video game practicing; group B) arms. Two weeks later, all
      students repeated the laparoscopic skills laboratory and were reassessed.
      RESULTS: Spearman correlation coefficients demonstrated a significant relation
      between many of the parameters, particularly time to complete each task and hand
      eye coordination at the different games. There was a weaker association between
      video game performance and both laparoscopic errors committed and hand-eye
      coordination. Group B subjects did not improve significantly over those in group
      A in any measure (P >0.05 for all). CONCLUSION: Video game aptitude appears to
      predict the level of laparoscopic skill in the novice surgeon. In this study,
      practicing video games did not improve one's laparoscopic skill significantly,
      but a larger study with more practice time could prove games to be helpful.

PMID- 15865531
TI  - Comparison of neuromuscular injuries to the surgeon during hand-assisted and
      standard laparoscopic urologic surgery.
AB  - BACKGROUND AND PURPOSE: Hand-assisted procedures have assumed a greater role in
      the practice of many laparoscopists. We surveyed major laparoscopy program
      directors to compare the incidence and location of neuromuscular injury to the
      surgeon during hand-assisted laparoscopic (HAL) and standard laparoscopic (SL)
      surgery. MATERIALS AND METHODS: A questionnaire on neuromuscular injuries was e
      mailed to 42 laparoscopic program directors. Respondents were instructed to
      report only injuries or pain associated with laparoscopic surgery when they were
      the primary responsible surgeon and not during open or endoscopic procedures.
      RESULTS: Surveys were returned from 23 attending laparoscopic surgeons and 2
      laparoscopic fellows. Surgeons reported an average of 3.9 HAL and 6.3 SL cases
      per month as the primary surgeon. The HAL was completed with the GelPort,
      LapDisk, Omniport, or a combination of devices 55%, 22%, 5%, and 14%,
      respectively, of the time. Comparing HAL with SL, there was significantly more
      hand/wrist, forearm, and shoulder pain/injuries associated with HAL (P < 0.004).
      There was significantly more neck pain associated with SL than HAL (P < 0.003),
      but no significant difference in lower-back pain (P = 0.40). Comparing the two
      most commonly used hand-assist devices (GelPort and LapDisk), the LapDisk
      demonstrated significantly more hand/wrist pain or injury (P = 0.001).
      CONCLUSION: Hand-assisted laparoscopy is associated with more frequent
      neuromuscular strain to the upper extremity than SL, but SL surgeons experience
      more neck pain or injury. Surgeon discomfort is also dependent on the type of
      hand-assist device. The long-term consequences of physical strain on the
      laparoscopic surgeon are unknown currently, but measures to minimize
      neuromuscular strain should be considered.

PMID- 15865532
TI  - Robot-assisted laparoscopic dismembered pyeloplasty: a combined experience.
AB  - BACKGROUND AND PURPOSE: The need for advanced laparoscopic skills limits the
      implementation of laparoscopic pyeloplasty to centers with extensive experience.
      The introduction of robotic technology into the field of minimally invasive
      surgery has facilitated complex surgical dissection and genitourinary
      reconstruction. We report our experience with robot-assisted laparoscopic
      pyeloplasty using the daVinci Surgical System at three New York City medical
      centers. PATIENTS AND METHODS: A retrospective review of all robot-assisted
      laparoscopic Anderson-Hynes dismembered pyeloplasty cases in 18 female and 17
      male patients between April 2001 and January 2004 was performed. The average
      patient age was 39.0 years (range 15-69 years). All patients had symptoms or
      radiographic evidence of ureteropelvic junction (UPJ) obstruction. Robotic
      assistance with the daVinci Surgical System was employed after preparation of the
      UPJ with a standard laparoscopic approach. RESULTS: The mean operative time and
      suturing time was 216.4 +/- 52.9 minutes and 63.0 +/- 14.2 minutes, respectively.
      The average estimated blood loss was minimal at 73.9 +/- 58.3 mL. The mean length
      of hospitalization was 69.4 hours (range 28-310 hours). The average use of
      intravenous morphine was 28.4 mg (range 0-162 mg). There were no intraoperative
      complications or open conversions. A mean follow-up of 7.9 months revealed a
      success rate of 94%, with two patients requiring further treatment. CONCLUSIONS:
      This combined multi-institutional series reveals that robot-assisted pyeloplasty
      with the daVinci Surgical System is safe and reproducible. These intermediate
      results appear comparable to those of open and laparoscopic pyeloplasty repairs.

PMID- 15865533
TI  - Computer-assisted laparoscopic pyeloplasty: University of Miami experience with
      the daVinci Surgical System.
AB  - PURPOSE: We report our experience with laparoscopic pyeloplasty using the daVinci
      surgical platform. PATIENTS AND METHODS: We routinely performed laparoscopic
      pyeloplasties prior to acquiring the daVinci system. We prospectively evaluated
      26 computer-assisted laparoscopic pyeloplasties (CLP) performed since acquiring
      the device in March 2003. There were 15 male and 11 female patients with a mean
      age of 34.5 years, who underwent right-sided procedures in 11 cases and left
      sided procedures in 15 cases. Four patients (15%) had secondary ureteropelvic
      junction obstruction. All procedures were performed through a transperitoneal
      approach over stents placed preoperatively. The operative time excluded the time
      needed for stent insertion. Radiographic objective success was defined as
      adequate cortical drainage (t (1/2) < or =15 minutes) and preserved or improved
      renal function on MAG-3 diuretic renography. RESULTS: A total of 23 dismembered
      pyeloplasties and 3 Y-V plasties were performed. In five patients, nephroscopy
      was performed for stone removal. The mean operative time and blood loss were 245
      minutes and 69 mL, respectively. There were no intraoperative complications or
      open conversions. Three minor postoperative complications were noted. The mean
      length of hospital stay was 2 days (range 1-5 days). In 19 evaluable patients, at
      a median follow-up of 6 months (range 2-10 days), 15 (79%) had complete symptom
      resolution, while 3 (16%) had marked symptom improvement. The overall subjective
      improvement rate thus was 95%. The objective success rate based on our strict
      diuretic renography criteria was 100%. The overall clinical success rate was 95%
      (18/19). CONCLUSIONS: Robot-assisted laparoscopic pyeloplasty is a feasible
      alternative to laparoscopic or open pyeloplasty with excellent short-term
      subjective and objective success rates.

PMID- 15865534
TI  - Technical modifications for robot-assisted laparoscopic pyeloplasty.
AB  - PURPOSE: Laparoscopic pyeloplasty (LP) is gaining acceptance as a standard of
      care for the repair of ureteropelvic junction (UPJ) obstruction, with results
      comparable to those of open repair. However, it remains a technically challenging
      procedure requiring intracorporeal suturing skills. Recent reports have
      demonstrated equally effective results with robot-assisted laparoscopy with
      shorter operative times. We present our modified technique for daVinci robot
      assisted LP. PATIENTS AND METHODS: From November 2002 to May 2004, 32 consecutive
      patients underwent LP with the daVinci robotic system for UPJ obstruction. Just
      prior to laparoscopy, 31 patients underwent retrograde pyelography and
      cystoscopic placement of a ureteral catheter just distal to the UPJ, which was
      prepared into the operative field. The remaining patient had an indwelling stent
      placed preoperatively. Three transperitoneal ports are placed for the robot. A
      fourth port is placed for retraction, suction, dissection, and suture passage by
      the bedside surgeon. This port was placed at McBurney's point in the first two
      patients and the subxiphoid area in the subsequent 30 patients. A ureteral stent
      was inserted retrograde intraoperatively with laparoscopic assistance after
      exchanging the ureteral catheter for a guidewire. A Jackson-Pratt drain was
      placed in all cases. RESULTS: All procedures were completed laparoscopically.
      Anderson-Hynes dismembered pyeloplasty was performed in 31 patients, while
      Fengerplasty was performed in 1 patient. The average operative time was 300
      minutes (initial 12 procedures: 384 minutes; last 10 procedures: 197 minutes).
      The average blood loss was approximately 50 mL and the average hospital stay 1.1
      days. A crossing vessel was present in 44% of the cases. Stone extraction was
      performed in 5 cases (23%) and kidney biopsy in 1 case. The only perioperative
      complications were one migrated stent, which was repositioned under sedation
      without sequelae and one urinary tract infection. Of the 18 patients with follow
      up exceeding 6 months (average 10.3 months), 16 have improved drainage and
      function and are asymptomatic. One patient with flank pain has no evidence of
      obstruction. One with delayed, although improved, drainage is asymptomatic.
      CONCLUSIONS: The daVinci robot system can be used effectively for LP. Although
      initial operative times were long, there was a significant decrease after the
      first 12 cases. Having retrograde access to the ureter allows simple
      intraoperative stent placement. We found that the subxiphoid placement of the
      fourth port gave the bedside surgeon the optimal location for suction,
      dissection, and intracorporeal suture passage. This approach and technique have
      become standard in our treatment of UPJ obstruction.

PMID- 15865535
TI  - Laparoscopic renal surgery in infants 10 kg or less.
AB  - BACKGROUND AND PURPOSE: Major laparoscopic urologic procedures have been
      successful in children, but few reports of laparoscopic surgery in infants
      weighing <10 kg exist. We present our series of laparoscopic renal procedures in
      such patients. PATIENTS AND METHODS: The hospital records of 17 consecutive
      patients (9 boys, 8 girls) with a median age of 7 months (range 1-25 months)
      weighing a mean of 8.5 kg (range 4.2-10 kg) who had undergone laparoscopic renal
      surgery (nephrectomy, partial nephrectomy, nephroureterectomy) between March 1999
      and January 2004 were reviewed. Twelve patients underwent laparoscopic
      nephrectomy, three laparoscopic nephroureterectomy, and two laparoscopic
      heminephrectomy. Additional procedures were performed concomitantly in three
      patients. RESULTS: All operations had minimal estimated blood loss. Excluding
      those patients who underwent additional procedures, the mean operative time was
      138 minutes (range 77-229 minutes). The postoperative hospitalization was 23
      hours or less in all except two patients, both of whom had undergone additional
      procedures. The only complication was an intraoperative diaphragmatic injury that
      was repaired laparoscopically without sequelae. There were no delayed
      complications, and by 2 weeks postoperatively, all patients were recovered fully.
      CONCLUSION: Major laparoscopic urologic procedures can be performed in infants
      weighing <10 kg with low morbidity and rapid recovery.

PMID- 15865536
TI  - Looped silk tie: surgical technique for management of the renal vein during
      laparoscopic live-donor nephrectomy.
AB  - Laparoscopic live-donor nephrectomy has revolutionized the field of kidney
      transplantation and has been adopted in many tertiary centers as the method of
      choice in procuring kidneys. While standard techniques for laparoscopic live
      donor nephrectomy have been well described in the literature, there continues to
      be ample discussion about renal-vein ligation. Endo-GIA and other commonly used
      vascular stapling devices can be costly and prone to mechanical failures and may
      not be applicable in certain anatomic situations. Vascular clips, although simple
      to use for arteries, are difficult to apply to large renal veins. To address
      these issues, we describe a simple, cost-effective method of control that can be
      used for both right and left renal veins, using a loop constructed from a 0 silk
      tie.

PMID- 15865537
TI  - Use of suspension traction system for renal positioning during laparoscopic
      partial nephrectomy.
AB  - BACKGROUND AND PURPOSE: The technical difficulty of laparoscopic partial
      nephrectomy (LPN) lies mainly in the steps required during warm ischemia time
      (WIT), which includes tumor excision and renal reconstruction. We present a renal
      suspension traction system to place the tumor in stable optimal view during the
      critical steps of LPN. PATIENTS AND METHODS: Thirty-three patients underwent LPN
      from October 2002 through December 2003. Eight had a renal sling placed
      intraoperatively because of difficult access to the tumor. Perioperative
      parameters were assessed. The renal hilum was dissected and the tumor exposed. To
      keep the tumor oriented perfectly toward the camera and the working ports, a 2-0
      braided polyglactin (Vicryl) traction suture was passed through Gerota's fascia,
      catching the renal capsule; brought out through the abdominal wall; and secured
      to the skin with a clamp. RESULTS: All surgical margins were negative. For the
      traction and nontraction groups, the mean sizes of the tumor were 2.5 cm and 2.2
      cm, respectively (P = 0.426). The estimated blood loss was 125 mL and 246 mL
      respectively (P = 0.041). The WIT average 27.4 minutes and 30.12 minutes (P =
      0.470). The surgical time was 192 minutes and 235 minutes respectively, (P =
      0.062). Based on our findings, we have devised a renal suspension traction
      algorithm for specific tumor locations during LPN. CONCLUSIONS: The renal
      suspension traction system allows precision in tumor excision and renal
      reconstruction during the critical steps of LPN. With the renal suspension system
      we devised, we are able to simplify LPN for tumors located away from optimal port
      access.

PMID- 15865538
TI  - Technique for ensuring negative surgical margins during laparoscopic partial
      nephrectomy.
AB  - BACKGROUND AND PURPOSE: Obtaining a negative surgical margin during laparoscopic
      partial nephrectomy (LPN) is paramount to optimizing the oncologic efficacy of
      the procedure. Limitations of laparoscopy hinder the ability to extrapolate the
      intraparenchymal tumor extension from the exophytic portion. We developed a
      technique wherein ultrasound-confirmed needle localization of the deep tumor
      margin prior to tumor extirpation ensured negative surgical margins. MATERIALS
      AND METHODS: Our technique was developed and initially tested using an agar-based
      ultrasound phantom designed to mimic 2-cm exophytic renal tumors. Needle
      placement was imaged with ultrasonography and subsequently correlated with
      findings on sectioning of the tumor mimic. Laparoscopic extirpation of the tumor
      mimic following needle placement was carried out in a pelvic trainer. The
      technique has subsequently been incorporated into our LPN technique in four
      patients. RESULTS: Ultrasound-confirmed needle localization of intraparenchymal
      tumor extension was feasible and reproducible in an ultrasound phantom.
      Ultrasound findings correlated with gross findings. Needle placement prior to
      tumor resection helped to ensure negative surgical margins when applied in the
      pelvic trainer and when used in three patients. In the remaining patient,
      improper needle placement resulted in a grossly positive deep margin. CONCLUSION:
      Ultrasound-confirmed needle placement effectively and reproducibly marks the deep
      margin of small renal tumors in a mimic as well as in vivo. Our needle technique
      eliminates the guesswork and unreliability associated with mental visualization
      and extrapolation of tumor extent during LPN.

PMID- 15865539
TI  - Ureteropelvic junction obstruction after partial nephrectomy.
AB  - BACKGROUND AND PURPOSE: As the experience with partial nephrectomy continues to
      grow and the procedure increasingly becomes the standard of care for properly
      selected patients, it is critical to understand the potential complications and
      how these complications are best managed. Presented herein is the presentation,
      work-up, and treatment of ureteropelvic junction (UPJ) obstruction after partial
      nephrectomy. PATIENTS AND METHODS: From 1993 to 2004, 1154 partial nephrectomies
      have been performed at our institution by one surgeon. From the database of these
      patients, four (0.35%) were identified with postoperative UPJ obstruction. The
      charts of these patients were reviewed to identify preoperative and
      intraoperative characteristics as they relate to the development and risk of UPJ
      obstruction. Additionally, the presentation of UPJ obstruction, its management,
      and long-term follow-up are reported. RESULTS: Tumor location in the lower pole
      appears to be a risk factor for the development of UPJ obstruction, which is
      likely a result of ischemic or mechanical injury. This complication was managed
      successfully by endoscopic approaches in three of four cases. At a mean follow-up
      of 43 months, all patients remain free of obstruction according to both the
      absence of symptoms and radiographic evidence. CONCLUSION: Obstruction of the UPJ
      is an uncommon complication of partial nephrectomy. Endoscopic treatment of this
      complication yields a durable outcome, as all patients with a mean follow-up of
      more than 3 years show resolution of their obstruction.

PMID- 15865540
TI  - Endoscopic injection of fibrin glue for the treatment of urinary-tract pathology.
AB  - BACKGROUND AND PURPOSE: Urinary-tract fistulas present unique clinical challenges
      that often necessitate open surgical excision with interposition of healthy
      tissue. Advances in retrograde instrumentation have enabled endourologists to
      employ more minimally invasive approaches to urologic disease, including
      fistulas. We reviewed our experience with endoscopic injection of fibrin glue for
      the treatment of urinary-tract pathology. PATIENTS AND METHODS: We performed a
      retrospective review of the eight patients at our institution who have undergone
      retrograde endoscopic injection of fibrin glue for the treatment of urinary-tract
      pathology. The data collected included age, presentation, treatment technique,
      method/duration of follow-up, complications, and success, which was defined as
      subjective and objective resolution of the treated pathology. RESULTS: One of
      these patients was treated for a caliceal diverticulum refractory to percutaneous
      ablation. The other seven patients were treated for fistulas, including one
      colovesical fistula, two vesicovaginal fistulas, one ileal conduit-cutaneous
      fistula, one ureterocutaneous fistula, one urethrocutaneous fistula, and one
      ureterorectal fistula. All lesions except the urethrocutaneous fistula and the
      ureterorectal fistula were treated with a single injection of fibrin glue. At a
      mean follow-up of 11.75 months, this technique was successful in six cases (75%).
      Two (33%) of the successfully treated patients required two injections. There
      were no complications. Failures were apparent at initial follow-up. CONCLUSION:
      Retrograde endoscopic injection of fibrin glue offers a novel approach to
      ablation of caliceal diverticula. Additionally, although open surgical excision
      of urinary-tract fistulae remains the gold standard treatment, endoscopic
      injection of fibrin glue offers a safe, minimally invasive approach that may
      avoid the morbidity of open surgery in such challenging patients.

PMID- 15865541
TI  - Laparoscopic prostate-sparing radical cystectomy: the Montsouris technique and
      preliminary results.
AB  - BACKGROUND AND PURPOSE: Prostate-sparing radical cystectomy has been described in
      the literature and has proven to be a promising procedure because of the
      continence and erectile function results which does not necessarily compromise
      the oncologic outcome in properly selected patients. We report our preliminary
      results with this technique performed laparoscopically. PATIENTS AND METHODS: A
      total of 25 patients with an average age of 60 years have undergone this
      procedure. Through a transperitoneal approach, lymph-node dissection is done with
      frozen-section examination, and the ureters are ligated and biopsied. The seminal
      vesicles are dissected, followed by complete mobilization of the bladder. Next
      the bladder neck is incised followed by the bladder-pedicle dissection. A simple
      prostatectomy can be performed if required. Finally, the neobladder is
      reconstructed via a small infraumbilical incision that also permits extraction of
      the surgical specimen. The neobladder is anastomosed to the prostate capsule.
      RESULTS: The average surgical time was 285 minutes and the mean blood loss 640
      mL. The complications encountered (4) were: one case each of bowel incarceration,
      urinary leak, lymphocele, and port-site hernia. All but one of the patients are
      alive at 9-month follow-up, with the one patient dying of cancer progression. No
      patient presented with daytime incontinence, although seven reported nocturia.
      There were 20 patients who maintained their preoperative sexual potency, and four
      described a decrease in erectile function postoperatively. CONCLUSIONS: We have
      been performing laparoscopic prostate-sparing radical cystectomy for more than 2
      years and have found it oncologically safe and reproducible with promising
      functional benefits. It presents a good option for properly selected patients.

PMID- 15865542
TI  - Effect of cystine-binding thiol drugs on urinary cystine capacity in patients
      with cystinuria.
AB  - PURPOSE: To determine the effect of cystine-binding thiol drugs (CBTD) on urinary
      cystine capacity in patients with cystinuria. PATIENTS AND METHODS: Seven
      cystinuric patients performed two sets of urine collections while on and off CBTD
      while controlling for all other variables: diet and fluid and alkali intake. They
      monitored and recorded their diet for 3 days and performed urine collections on
      days 2 and 3. They then stopped the CBTD for 7 days. On days 8, 9, and 10, they
      replicated their diets of days 1 through 3 and performed two more urine
      collections on days 9 and 10. Two patients took D-penicillamine, four took
      tiopronin, and one took tiopronin and captopril. The cystine capacity was
      determined, and the values obtained when the patient was on and off the CBTD were
      compared to determine whether CBTDs affect urinary cystine capacity. To measure
      the cystine capacity, we used a solid-phase assay in which cystine crystals are
      added to the urine and incubated for 48 hours. The crystals are spun down and
      resolubilized in high-pH buffer, and the amount of cystine in the crystals is
      calculated. The solid phase will take up cystine from urine (negative cystine
      capacity) that is supersaturated and give up cystine to an undersaturated urine
      (positive cystine capacity). RESULTS: All seven patients had significant
      improvement in urinary cystine capacity on CBTDs. The mean cystine capacity off
      CBTD was -130.6 +/- 280.8, while the value during CBTD use was 43.1 +/- 131.2 (P
      < 0.05). On CBTDs, two patients still had negative values, but both had important
      improvements. The mean urinary volumes were similar on and off CBTD, indicating
      adequate and similar fluid intake. Urine pH values and urinary excretion of
      sodium and urea also were comparable, indicating consistency of citrate intake
      and diet. CONCLUSIONS: Our results demonstrate that CBTDs lower the urinary
      supersaturation of cystine, as shown by a less-negative or more-positive cystine
      capacity. Cystine capacity can be measured directly, even in the presence of
      CBTDs. The value of this measurement lies in the potential to monitor the
      response to the drug, prescribe the minimum effective dose, and potentially
      decrease the adverse effects often associated with CBTDs.

PMID- 15865546
TI  - The arrogance of power unchecked--the terrible, grotesque tragedy of the case of
      Terri Schiavo.

PMID- 15865547
TI  - Surgical infection control. Surgical Infection Society--Europe presidential
      address.

PMID- 15865548
TI  - The truth is in the dialogue. Surgical Infection Society--Europe Semmelweis
      Lecture.

PMID- 15865549
TI  - An open-label, randomized study comparing efficacy and safety of intravenous
      piperacillin/tazobactam and ampicillin/sulbactam for infected diabetic foot
      ulcers.
AB  - BACKGROUND: Soft tissue and bone infections of the lower limb continue to be a
      frequent and serious complication in patients with diabetes mellitus. The best
      choice of antimicrobial for the empiric treatment of moderate to severe diabetic
      foot infections has not been established clearly. METHODS: We conducted a
      prospective, randomized, open-label, multicenter trial comparing
      piperacillin/tazobactam (P/T) (4 g/0.5 g q8h) and ampicillin/sulbactam (A/S) (2
      g/1 g q6h) as a parenteral treatment for 314 adult patients with moderate-to
      severe infected diabetic foot ulcers. Patients with polymicrobial infections
      involving methicillin-resistant Staphylococcus aureus also received vancomycin 1
      g q12h. RESULTS: Clinical efficacy rates (cure or improvement) were statistically
      equivalent overall (81% for P/T vs. 83.1% for A/S), and median duration of
      treatment was similar in the clinically evaluable populations (nine days for P/T,
      10 days for A/S). Drug-related adverse events for both study drugs were
      comparable in frequency and type. CONCLUSIONS: Although both study drugs provide
      safe and effective empiric treatment for moderate-to-severe infected diabetic
      foot ulcers, piperacillin/tazobactam has the advantage of covering Pseudomonas
      aeruginosa (bacteriologic success rate of 85.7%), the most commonly isolated gram
      negative pathogen in this study.

PMID- 15865550
TI  - Influence of antibiotic therapy on mortality of critical surgical illness caused
      or complicated by infection.
AB  - BACKGROUND: Conceptually, appropriateness of antibiotic therapy includes choice
      of agent relative to susceptibility of pathogens as well as dosing, timing of
      onset, and duration of therapy, but is most commonly considered in terms of
      choice of antibiotic. It has been suggested that inappropriate antibiotic
      selection can result in increased mortality. This study was performed to
      elucidate the role of scheduled, rotating antibiotic therapy in defining
      mortality among febrile, infected surgical ICU patients. METHODS: Prospective
      inception-cohort study of 356 patients during their initial episode of fever
      (temperature > 38.2 degrees C), caused by infection diagnosed by positive
      cultures or direct inspection (some cases of peritonitis). Collected data
      included age, gender, admission APACHE III score, peak temperature, microbial
      isolates and susceptibility, source of infection, multiple organ dysfunction
      score, mortality, and several time intervals (time that cultures were collected,
      time from collection to antibiotic prescription, time from collection to
      antibiotic administration, duration of therapy). RESULTS: The mean age was 63 +/-
      1 years, the mean APACHE III score was 74 +/- 2 points, the mean multiple organ
      dysfunction score was 8 +/- 1 points, and overall mortality was 31%. Neither the
      source of infection nor the specific isolate influenced mortality. Antibiotic
      therapy was appropriate (covered the isolates) in 94% of cases, and did not
      influence mortality. Duration of therapy was identical between groups (5.1 +/-
      0.3 vs. 5.4 +/- 0.3 days, p = 0.61). By logistic regression (dependent variable =
      mortality), APACHE III score OR 1.025, 95% C.I. 1.021-1.04) and delayed
      antibiotic administration (30-min intervals, OR 1.021, 95% C.I. 1.003-1.038) were
      independent predictors of mortality. CONCLUSIONS: The use of scheduled monthly
      antibiotic cycling in the surgical ICU is associated with a high rate of
      "appropriate" antibiotic therapy, and appears to maintain or improve resistance
      patterns. Because antibiotic therapy was mostly appropriate for isolates, initial
      inappropriate therapy could not be identified as a risk factor for mortality.
      However, in the setting of appropriate antibiotic choice, the prompt initial
      administration of antibiotics appears to be crucial for survival, but neither
      site of infection nor specific pathogen are influential.

PMID- 15865551
TI  - Comparison of fungal and nonfungal infections in a broad-based surgical patient
      population.
AB  - BACKGROUND: Our aim was to compare fungal and nonfungal infections among a
      diverse surgical patient population. METHODS: Data on all hospital-acquired
      infectious episodes among surgical intensive care unit and ward patients were
      collected prospectively over six years at a single university hospital. The
      relationships between fungal and nonfungal infection and over 100 variables were
      examined using univariate and multiple logistic regression analysis. RESULTS:
      During the study period, 3,980 infectious episodes were identified; 554 were
      associated with fungal infection. Multiple logistic regression analysis
      demonstrated that markers of severity of acute illness (higher APACHE II scores
      and white blood cell counts, greater transfusion of cellular blood products,
      mechanical ventilator dependency, and prior infection) predicted fungal
      infection, whereas markers of chronic illness (comorbidities) did not
      independently predict either fungal or nonfungal infection. Patients with fungal
      infection were treated with more antibiotics for longer periods of time, had
      prolonged lengths of stay, and more often died compared with nonfungal infection
      patients. A separate multiple logistic regression analysis demonstrated that both
      fungal infection and the number of fungal sites of infection independently
      predicted mortality. Of all fungal isolates, only Candida albicans and
      Aspergillus spp. independently predicted mortality. CONCLUSIONS: Fungal
      infections differ significantly in character and outcomes from nonfungal
      infections among surgical patients.

PMID- 15865552
TI  - Cost of a ventilator-associated pneumonia in a shock trauma intensive care unit.
AB  - BACKGROUND: Nosocomial pneumonia and especially ventilator-associated pneumonia
      (VAP) are costly complications for the hospitalized patient. Nosocomial pneumonia
      has been estimated to cost $5,000 per episode, but the specific cost for a VAP
      has not been well estimated. As part of a successful performance improvement
      program in decreasing VAP from 10 VAPs/100 ICU admissions to 2.5 VAPs/100 ICU
      admissions, we examined the costs associated with VAP. METHODS: From January 1,
      2002, through September 30, 2003, Shock Trauma Intensive Care Unit patients and
      charts were reviewed concurrently by an infection control practitioner for
      development of VAP as defined by National Nosocomial Infection Surveillance
      (NNIS) guidelines. Costs were obtained from the hospital's cost accounting
      software Transition Systems version 3.1.01 (TSI). All patients requiring greater
      than one day of mechanical ventilation were evaluated. Seventy patients with VAP
      and 70 patients without VAP were matched according to age and Injury Severity
      Score. Differences were compared using Kruskal-Wallis and two sample T-tests.
      Significance was considered for p < 0.05. RESULTS: The ICU cost difference was
      significant (p < 0.05) between the case-controlled patients with VAP ($82,195)
      and those without VAP ($25,037). There was also a significant increase in ICU
      length of stay (21.6 versus 6.4 days) and the number of ventilator days (17.7
      versus 5.8; both, p < 0.05). Mortality was not different in the case-controlled
      population. A substantial portion of the increased cost of a VAP was from the
      increase in ICU length of stay ($1,861/day). Pharmacy, respiratory and "other"
      also accounted for the increases when cost distribution was analyzed. This
      translates into a cost avoidance of approximately $428,685 per 100 admissions to
      the ICU. CONCLUSIONS: Ventilator-associated pneumonia not only leads to a
      significant increase in ventilator days and ICU length of stay, but adds
      substantially to hospital costs. In our ICU, an episode of VAP costs $57,000 per
      occurrence.

PMID- 15865553
TI  - Nonspecific phosphodiesterase inhibition attenuates liver injury in acute
      endotoxemia.
AB  - BACKGROUND: Endotoxemia is accompanied by pro-inflammatory cytokine production,
      generation of reactive oxygen species, and end-organ injury. Pentoxifylline
      (PTX), a methylxanthine derivative and phosphodiesterase inhibitor, is known for
      its anti-inflammatory properties, including down-regulation of interleukin (IL)-6
      and tumor necrosis factor (TNF)-alpha synthesis. Its effects on liver function
      and hepatic histology following acute endotoxemia have not been investigated
      fully. We hypothesized that PTX would preserve liver architecture and function
      after intravenous lipopolysaccharide (LPS) injection. METHODS: Anesthetized
      Sprague-Dawley rats received an i.v. bolus injection of LPS (5 mg/kg), LPS + PTX
      (25 mg/kg), or saline (sham). Plasma concentrations of alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), TNF-alpha, IL-6, and nitrite were
      measured at different time points after LPS injection. Liver injury was graded
      according to a scoring system in a blinded fashion from 0 (normal) to 4 (severe)
      for hepatocellular necrosis, hemorrhage, and parenchymal and sinusoidal
      inflammatory infiltrates. Neutrophil infiltration was measured by counting
      myeloperoxidase (MPO)-positive stained cells. Nuclear factor (NF)-kappaB p-65 was
      measured by counting positive stained nuclei of hepatocytes and Kupffer cells
      (KC). Inducible nitric oxide synthase (iNOS) was evaluated by positively stained
      KC. Data are presented as mean +/- SEM. Analysis of variance with p < 0.05 was
      considered statistically significant. RESULTS: Animals treated with PTX showed a
      significant reduction in liver injury score and neutrophil infiltration.
      Treatment with PTX significantly decreased TNF-alpha, IL-6, and the
      concentrations of AST and ALT when compared to LPS alone. In addition, a
      significant decrease in NF-kappaB-positive staining in hepatocytes and KC, as
      well as in KC iNOS immunostaining was observed in PTX-treated animals compared to
      the LPS group. CONCLUSIONS: Pentoxifylline downregulates the inflammatory
      response significantly and decreases liver injury in acute endotoxemia.

PMID- 15865554
TI  - Emerging infections with community-associated methicillin-resistant
      Staphylococcus aureus in outpatients at an Army Community Hospital.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection
      typically occurs in chronically ill patients requiring long-term antimicrobial
      therapy or hospitalization. However, community-associated MRSA (CA-MRSA)
      necrotizing soft tissue infections seem to be increasing in incidence. Our aim
      was to describe the incidence and microbiologic characteristics of CA-MRSA
      isolates collected at an army community hospital. METHODS: We report a
      retrospective review of MRSA isolates identified during 1998-2003 at the
      microbiology laboratory of Moncrief Army Community Hospital that serves a
      community of approximately 40,000 transient residents yearly in Fort Jackson,
      South Carolina. We evaluated the incidence of MRSA in our laboratory during 1998
      2003. For MRSA isolates from 2003, we evaluated antimicrobial susceptibility
      patterns. Six selected isolates were evaluated by molecular typing, resistance
      gene analysis, and toxin analysis. RESULTS: During 1998-2003, 241 (23%) of 1041
      S. aureus isolates identified at the hospital microbiology laboratory were
      resistant to methicillin. Of these 241 MRSA isolates, 223 were cultured from
      outpatients. The incidence of MRSA in our population increased from 12% of S.
      aureus isolates in 1998 to 43% in 2003. In 2003, MRSA was cultured from 76
      different patients. Isolates of MRSA were often resistant to erythromycin (91%),
      although resistance to other agents was less common: Ciprofloxacin (14%),
      levofloxacin (14%), clindamycin (3%), tetracycline (3%), and trimethoprim
      sulfamethoxazole (1%). No isolates were resistant to vancomycin, gentamicin,
      nitrofurantoin, or rifampin. Six CA-MRSA isolates were compared by pulsed-field
      gel electrophoresis (PFGE). Five were PFGE type USA300, and one was PFGE type
      USA100, based on the U.S. Centers for Disease Control and Prevention (CDC)
      classification scheme. The five USA300 isolates carried SCCmec type IV, and the
      USA100 carried SCCmec II. None of the isolates were positive by PCR for genes
      encoding enterotoxins A-E and H, or toxic shock syndrome toxin (TSST-1), but the
      five USA300 isolates carried the gene coding for Panton-Valentine leukocidin
      toxin. CONCLUSIONS: The incidence of MRSA at our institution is increasing.
      Isolates of MRSA show resistance patterns and microbiologic characteristics
      consistent with CA-MRSA isolates from the United States. Clinicians should
      consider the possibility of CA-MRSA in patients with soft-tissue infections who
      do not respond to initial therapy with beta-lactam antimicrobial agents.

PMID- 15865555
TI  - Primary peritonitis with Staphylococcus epidermidis following prosthetic spinal
      surgery.

PMID- 15865561
TI  - Sex education and unintended pregnancy: are we seeing the results?

PMID- 15865562
TI  - Late terminations of pregnancy--an obstetrician's perspective.

PMID- 15865563
TI  - Abortion in Australia: a legal misconception.

PMID- 15865564
TI  - Sink or swim--ageing in Australia.
AB  - As the number of people under the age of 65 declines, the number over 65 will
      double in the next half century, Australia. By 2031, it is estimated those over
      65 will account for more than a quarter of the Australian population. The fastest
      rate of growth will be in the over-85-years category, projected to double over
      the next 20 years and to triple over 50 years to include 2.3 million people.
      Health care providers cannot afford to wait for the inevitable crises this vast
      demographic shift will provoke. To meet these future demands, educational and
      health care institutes should consider establishing interdisciplinary think-tanks
      for multidisciplinary research, policy development and innovations in aged care
      and health service delivery.

PMID- 15865565
TI  - Geriatric interventions: the evidence base for comprehensive health care services
      for older people.
AB  - Specialist geriatric services apply a comprehensive, multidisciplinary evaluation
      and management approach to the multidimensional and usually interrelated medical,
      functional and psychosocial problems faced by at-risk frail elderly people. This
      paper examines currently available data on geriatric interventions and finds
      ample evidence supporting both the efficacy and the cost-effectiveness of these
      specialist interventions when utilised in appropriately targeted patients. It is
      proposed that substantial investment in these programs is required to meet the
      future demands of Australia's ageing population.

PMID- 15865566
TI  - Nursing in Australian general practice: directions and perspectives.
AB  - Primary health care services, such as general practices, are the first point of
      contact for many Australian health care consumers. Until recently, the role of
      nursing in Australian primary care was poorly defined and described in the
      literature. Changes in policy and funding have given rise to an expansion of the
      nursing role in primary care. This paper provides a review of the literature and
      seeks to identify the barriers and facilitators to implementation of the practice
      nurse role in Australia and identifies strategic directions for future research
      and policy development.

PMID- 15865567
TI  - Distributional impact of recent changes in private health insurance policies.
AB  - The impacts of changes to private health insurance (PHI) policies introduced
      since 1999 - in particular the 30% PHI rebate and the Lifetime Health Cover -
      have been much debated. We present historical analyses of the impacts in terms of
      the proportion of Australians having hospital insurance cover under different PHI
      policies, by age, gender and socioeconomic status, and project these to 2010
      using a new Private Health Insurance coverage model. The combined effect of the
      30% rebate and Lifetime Health Cover was to increase PHI membership from just
      over 30% in 1998 to just under 50% by the end of 2000, due mainly to more people
      taking out PHI cover from among the richest 20% of the population. Among the
      poorest 40% the impact was minimal. Model projections suggested that, had the new
      PHI policies not been introduced, then the proportion of Australians with PHI
      would have declined to around 20% by 2010, compared with 40% if the current
      arrangements remained in place. Also, analysis of 2001 survey data regarding
      choices to use a public or a private hospital indicated that higher income groups
      with or without PHI were the more likely to have used a private hospital than
      lower income groups. Among those with PHI, older people were more likely to have
      used a private hospital than younger ones.

PMID- 15865568
TI  - Are Victorian elective surgery cases still converting from overnight to same day
      cases?
AB  - The conversion rate on a diagnosis related group (DRG)-standardised basis of
      Victorian private overnight (ON) elective surgery cases to same day (SD) cases
      declined from 4.7% per annum over 1996-97 to 1998-99 to 2.5% per annum over 1998
      99 to 2002-03. Similar analysis within the Victorian public sector shows a
      decline from 3.8% per annum over 1996-97 to 1998-99 to 1.9% over 1998-99 to 2002
      03. Comparison on a DRG-standardised basis shows while the public sector
      continued to show a higher incidence of elective surgery SD cases than the
      private sector in 2002-03 (by 1.6%). The difference has declined since 1998-99
      when it was 2.4%. DRG-based analysis suggests the conversion rate in both sectors
      and the difference in SD surgery cases between the two sectors will continue to
      decline. Future savings in recurrent and capital cost due to ON surgery cases
      becoming SD cases are likely to be much lower than savings in recent years.

PMID- 15865569
TI  - What employment programs should health services invest in for people with a
      psychiatric disability?
AB  - Employment has significant health benefits for people with a psychiatric
      disability, including improved mental health and wellbeing and a reduction in
      symptoms and rates of relapse. Systematic reviews show that supported employment
      is more effective than prevocational training in achieving open employment for
      this group. Health services should invest in developing partnerships and
      structures to ensure access to evidence-based supported employment programs for
      people with a psychiatric disability. We draw on exploratory research in south
      west Sydney to discuss some of the challenges that a focus on employment presents
      for mental health services.

PMID- 15865570
TI  - Lessons from the National Mental Health Integration Program.
AB  - Three projects were funded under the national Mental Health Integration Program
      (MHIP) in 1999, each of which employed a different model aimed at improving
      linkages between disparate parts of the mental health system. A national
      evaluation framework guided local evaluations of these projects, and this paper
      presents a synthesis of the findings. For providers, the projects improved
      working relationships, created learning opportunities and increased referral and
      shared care opportunities. For consumers and carers, the projects resulted in a
      greater range of options and increased continuity of care. For the wider system,
      the projects achieved significant structural and cultural change. Cost-wise,
      there were no increases in expenditure, and even some reductions. Many of the
      lessons from the projects (and their evaluations) may be generalised to other
      mental health settings and beyond.

PMID- 15865571
TI  - Health workforce design for the 21st century.
AB  - The Australian health workforce has changed dramatically over the last 4 years,
      growing in size and changing composition. However, more changes will be needed in
      the future to respond to the epidemiological and demographic transition of the
      Australian population. A critical issue will be whether the supply of health
      professionals will keep pace with demand. There are current recorded shortages of
      most health professionals, but this paper argues that future workforce planning
      should not be based on providing more of the same. Rather, the roles of health
      professionals will need to change and workforce planning needs to place a
      stronger emphasis on issues of workforce substitution, that is, a different mix
      of responsibilities. This will also require changes in educational preparation,
      in particular an increased emphasis on interprofessional work and common
      foundation learning.

PMID- 15865572
TI  - Evaluating the effectiveness of health care teams.
AB  - While it is recognised that effective health care teams are associated with
      quality patient care, the literature is comparatively sparse in defining the
      outcomes of effective teamwork. This literature review of the range of
      organisational, team and individual benefits of teamwork complements an earlier
      article which summarised the antecedent conditions for (input) and team processes
      (throughput) of effective teams. This article summarises the evidence for a range
      of outcome measures of effective teams. Organisational benefits of teamwork
      include reduced hospitalisation time and costs, reduced unanticipated admissions,
      better accessibility for patients, and improved coordination of care. Team
      benefits include efficient use of health care services, enhanced communication
      and professional diversity. Patients report benefits of enhanced satisfaction,
      acceptance of treatment and improved health outcomes. Finally, team members
      report enhanced job satisfaction, greater role clarity and enhanced well-being.
      Due to the inherent complexity of teamwork, a constituency model of team
      evaluation is supported where key stakeholders identify and measure the intended
      benefits of a team.

PMID- 15865573
TI  - To be or not to be . . . a manager: the career choices of health professionals.
AB  - This paper focuses on decisions made by professionals working in the health
      industry who have, at some stage in their career, considered taking on a
      management role. It describes some of the factors that appear to influence their
      decisions. The study, based on 60 interviews with professionals working in the
      health industry, identified six different categories in terms of their approach
      and attitudes to taking on management roles. The paper concludes with an analysis
      of the implications for people considering a management career in the health
      industry.

PMID- 15865574
TI  - Public health job vacancies--who wants what, where?
AB  - This paper presents a snapshot of job vacancies in the public health workforce
      labour market. The analysis is based on 404 advertised public health jobs
      appearing in the press, and on-line job alerts over a 2-month period in mid 2003.
      The analysis reveals who was seeking employees, what formal qualifications and
      competencies were required, what salary and other conditions of employment were
      offered and where the vacant jobs were located. The study demonstrates the
      heterogeneity of the public health workforce, which limits definition of clear
      practice boundaries and complicates workforce planning. The findings further
      demonstrate the benefit of reviewing both the demand and the supply side of the
      labour market, and point to the value of repeated surveys of advertised jobs as
      part of an ongoing public health workforce monitoring and planning process.

PMID- 15865575
TI  - Long-stay views from the hospital bed: patient perspectives of organisation of
      care and impact of hospitalisation.
AB  - This study aimed to determine the perspectives of a group of patients categorised
      as "long-stay outliers" at a large South Australian metropolitan hospital about
      aspects of organisation of care and the perceived impact of long-term
      hospitalisation, Australia. Nineteen patients were interviewed using a semi
      structured questionnaire. Eighty-nine percent of participants stated that they
      had no knowledge of how long they were to be in hospital. Forty-two percent
      indicated that they did not know when they would be discharged from hospital.
      This was of concern, especially considering the vulnerability of this patient
      group and the known benefits of patient involvement in decision making and the
      improvements this can make to health outcomes and early discharge. Participants
      indicated concern about sleep deprivation, diet, ability to return to paid
      employment, and missing their family as the main areas of impact of their long
      hospitalisation. Concerns about being discharged from hospital included:
      apprehension as to whether they were well enough to leave; the recurrence of
      infection; whether they would be able to sleep well when they got home; their
      recent loss of appetite and associated weight loss; mobility concerns; and what
      supports they would have when they were discharged home. All these issues require
      staff to be more patient and family-centred in their approach to preparing for
      discharge.

PMID- 15865576
TI  - Blood transfusion prescribing in the ACT: an insight into clinical decision
      making.
AB  - Medical practitioners with varying levels of experience may make medical
      decisions in hospitals. Little is known about who is responsible for these
      decisions. We determined transfusion appropriateness during an audit of blood
      transfusion, before developing practice improvement strategies, by concurrent
      medical record review. The prescriber could be determined in 78% of transfusion
      episodes: most were specialist staff. Registrars and after-hours staff prescribed
      significantly fewer inappropriate transfusions. The findings have significant
      implications in understanding clinical decision making in the hospital setting
      and for the targeting of quality improvement strategies in particular.

PMID- 15865577
TI  - Management of delirium: a clinical governance approach.
AB  - This study assessed the management of delirium in the Acute Care of the Elderly
      unit (ACE) at a tertiary referral hospital as a case study of the application of
      clinical governance principles. The environment was found to be supportive of
      ongoing clinical governance activities, both in clinical organisation of work
      processes and orientation of management. However, patient involvement,
      dissemination and use of clinical pathways, performance measurement and feedback,
      and maintaining stability of care are areas requiring further development.
      Although there is a clinical governance strategy in place at the policy level,
      this has not always filtered through to the level of clinical work.

PMID- 15865579
TI  - The effects of increased private health insurance: a review of the evidence.

PMID- 15865580
TI  - National data elements for the clinical management of acute coronary syndromes.
AB  - Patients with acute coronary syndromes represent a clinically diverse group and
      their care remains heterogeneous. These patients account for a significant burden
      of morbidity and mortality in Australia. Optimal patient outcomes depend on rapid
      diagnosis, accurate risk stratification and the effective implementation of
      proven therapies, as advocated by clinical guidelines. The challenge is in
      effectively applying evidence in clinical practice. Objectivity and standardised
      quantification of clinical practice are essential in understanding the evidence
      practice gap. Observational registries are key to understanding the link between
      evidence-based medicine, clinical practice and patient outcome. Data elements for
      monitoring clinical management of patients with acute coronary syndromes have
      been adapted from internationally accepted definitions and incorporated into the
      National Health Data Dictionary, the national standard for health data
      definitions in Australia. Widespread use of these data elements will assist in
      the local development of "quality-of-care" initiatives and performance
      indicators, facilitate collaboration in cardiovascular outcomes research, and aid
      in the development of electronic data collection methods.

PMID- 15865581
TI  - Obstetricians and midwives modus vivendi for current times.
AB  - Obstetric services need to be women-centred and based on mutual respect and
      collaboration.

PMID- 15865582
TI  - A picture of Australia's children.
AB  - Do we have a clear enough picture to guide rational health and social policy
      responses?

PMID- 15865583
TI  - Friedreich ataxia: from genes to therapies?
AB  - Most cases are caused by a single mutation, paving the way for therapeutic
      advances for this fatal disease.

PMID- 15865584
TI  - Gene therapy: great expectations?
AB  - Unrealistic expectations may overshadow genuine advances and focus attention more
      on failures.

PMID- 15865585
TI  - Oversight and monitoring of clinical research with gene therapy in Australia.
AB  - The NHMRC has set up the Gene and related Therapies Research Advisory Panel
      (GTRAP) to oversee gene therapy research.

PMID- 15865586
TI  - 24/7 Health. Second annual Sleep Loss Symposium: working and sleeping around the
      clock.

PMID- 15865587
TI  - Estimating Australia's abortion rates 1985-2003.
AB  - AIM: To estimate national rates of induced abortion in Australia from 1985 to
      2003, using Medicare claim statistics for private patients and hospital morbidity
      statistics for public patients. DESIGN AND SETTING: Estimates were based on
      Australian and South Australian data collections relating to abortions. SA
      hospital morbidity statistics were compared with SA statutory notifications of
      abortions to estimate the accuracy of these collections. Medicare statistics on
      abortion procedures performed on private patients in South Australia were then
      compared with hospital morbidity statistics for private patients. National
      statistics on abortion derived from Medicare and hospital morbidity statistics
      were adjusted for inaccuracies found in these sources. MAIN OUTCOME MEASURES:
      Numbers of induced abortions in Australia for each year from 1985 to 2003;
      abortion rates per 1000 women aged 15-44 years. RESULTS: Abortion numbers based
      on Medicare claims by private patients overestimated by 18.7% the number of
      abortions derived from statutory notifications in South Australia during the
      period 1988-89 to 1999-00. Hospital morbidity data using principal diagnosis
      codes relating to medical abortion overestimated statutory notifications by 2.3%
      (mainly because of readmissions). National statistics were adjusted for these
      overestimations and for the estimated 14.1% of private patients who would not
      have submitted Medicare claims (based on surveys of private-clinic patients in
      New South Wales and Victoria). The estimated Australian abortion rate increased
      from 17.9 per 1000 women aged 15-44 in 1985 to a peak of 21.9/1000 in 1995, then
      declined to 19.7/1000 in 2003 (estimated number of abortions, 84,460).
      CONCLUSION: There are no data currently available for deriving accurate numbers
      of induced abortions in Australia. Suggestions are made for collection of
      national statistics.

PMID- 15865588
TI  - The Australian Cancer Anaemia Survey: a snapshot of anaemia in adult patients
      with cancer.
AB  - OBJECTIVE: To evaluate the frequency and management of anaemia in Australian
      adults with solid and haematological malignancies. DESIGN: 6-month observational,
      prospective, multicentre study. PARTICIPANTS: 694 patients recruited from
      outpatient oncology clinics in 24 hospitals in five Australian states between 9
      April 2001 and 31 July 2001. MAIN OUTCOME MEASURES: Frequency of anaemia
      (haemoglobin [Hb] level < 120 g/L) at enrolment and over ensuing 6 months, by
      tumour type, disease status and cancer treatment; anaemia treatment and "trigger"
      Hb level for this treatment. RESULTS: Participants had median age 60 years, and
      61% were women. Prevalence of anaemia at enrolment was 35% (199/562), with 78% of
      these 199 having mild anaemia (Hb, 100-119 g/L). Frequency of anaemia (either
      present at enrolment or developing during the study) was 57% overall (323/566),
      and varied with tumour type, from 49% (lymphoma/myeloma) to 85% (urogenital
      cancer). Patients who received radiotherapy either in combination or concomitant
      with chemotherapy were more likely to have anaemia (73%) than those receiving
      chemotherapy alone (58%) (P = 0.004). Of all chemotherapy patients not anaemic at
      enrolment, 23% developed anaemia by the second monthly follow-up. Independent
      predictors for anaemia in chemotherapy patients were low baseline Hb level (odds
      ratio [OR], 5.4; 95% CI, 2.7-10.9) and use of platinum chemotherapeutic agents
      (OR, 4.8; 95% CI, 2.1-11.4) (P < 0.001). Anaemia was treated in 41% of patients
      with anaemia at enrolment--by transfusion (36%), iron (5%) and erythropoietic
      agents (2%). Frequency of anaemia treatment varied between tumour types, from 19%
      (breast cancer) to 60% (leukaemia). The mean "trigger Hb" for initiating
      transfusion was 95 g/L. CONCLUSIONS: Anaemia is prevalent among Australian
      patients with cancer managed in hospital oncology units. Its management varies
      between tumour types. Many patients do not receive treatment for their anaemia.

PMID- 15865589
TI  - Treatment of an infant with X-linked severe combined immunodeficiency (SCID-X1)
      by gene therapy in Australia.
AB  - OBJECTIVE: To report the outcome of gene therapy in an infant with X-linked
      severe combined immunodeficiency (SCID-X1), which typically causes a lack of T
      and natural killer (NK) cells. DESIGN AND SETTING: Ex-vivo culture and gene
      transfer procedures were performed at The Children's Hospital at Westmead,
      Sydney, NSW, in March 2002. Follow-up to March 2005 (36 months) is available.
      PATIENT: A 9-month-old male infant with confirmed SCID-X1 (including complete
      absence of T cells) with an NK+ phenotype (a less common variant of SCID-X1), and
      no HLA-identical sibling donor available for conventional bone marrow
      transplantation. PROCEDURE: CD34+ haemopoietic progenitor cells were isolated
      from harvested bone marrow and cultured with cytokines to stimulate cellular
      replication. Cells were then genetically modified by exposure to a retrovirus
      vector encoding human gamma c (the common gamma chain of several interleukin
      receptors; mutations affecting the gamma c gene cause SCID-X1). Gene-modified
      cells (equivalent to 1.3 x 10(6) CD34+/gamma c+ cells/kg) were returned to the
      infant via a central line. RESULTS: T cells were observed in peripheral blood 75
      days after treatment, and levels increased rapidly to 0.46 x 10(9) CD3+ cells/L
      at 5 months. Within 2 weeks of the appearance of T cells, there was a distinct
      clinical improvement, with early weight gain and clearance of rotavirus from the
      gut. However, T-cell levels did not reach the reference range, and immune
      reconstitution remained incomplete. The infant failed to thrive and developed
      weakness, hypertonia and hyperreflexia in the legs, possibly the result of immune
      dysregulation. He went on to receive a bone marrow transplant from a matched
      unrelated donor 26 months after gene therapy. CONCLUSIONS: This is the first
      occasion that gene therapy has been used to treat a genetic disease in Australia.
      Only partial immunological reconstitution was achieved, most likely because of
      the relatively low dose of gene-corrected CD34+ cells re-infused, although viral
      infection during the early phase of T-cell reconstitution and the infant's NK+
      phenotype may also have exerted an effect.

PMID- 15865590
TI  - The Australasian Society of Clinical Immunology and Allergy position statement:
      Summary of allergy prevention in children.
AB  - A family history of allergy and asthma identifies children at high risk of
      allergic disease. Dietary restrictions in pregnancy are not recommended. Avoiding
      inhalant allergens during pregnancy has not been shown to reduce allergic
      disease, and is not recommended. Breastfeeding should be recommended because of
      other beneficial effects, but if breast feeding is not possible, a hydrolysed
      formula is recommended (rather than conventional cow's milk formulas) in high
      risk infants only. Maternal dietary restrictions during breastfeeding are not
      recommended. Soy formulas and other formulas (eg, goat's milk) are not
      recommended for reducing food allergy risk. Complementary foods (including normal
      cow's milk formulas) should be delayed until a child is aged at least 4-6 months,
      but a preventive effect from this measure has only been demonstrated in high-risk
      infants. There is no evidence that an elimination diet after age 4-6 months has a
      protective effect, although this needs additional investigation. Further research
      is needed to determine the relationship between house dust mite exposure at an
      early age and the development of sensitisation and disease; no recommendation can
      yet be made about avoidance measures for preventing allergic disease. No
      recommendations can be made about exposure to pets in early life and the
      development of allergic disease. If a family already has pets it is not necessary
      to remove them, unless the child develops evidence of pet allergy (as assessed by
      an allergy specialist). Women should be advised not to smoke while pregnant, and
      parents should be advised not to smoke. No recommendations can be made on the use
      of probiotic supplements (or other microbial agents) for preventing allergic
      disease at this time. Immunotherapy may be considered as a treatment option for
      children with allergic rhinitis, and may prevent the subsequent development of
      asthma.

PMID- 15865591
TI  - Improving the governance of health research.
AB  - Australia has so far been spared serious mishaps in health research, but rising
      pressures on researchers, deemed to have contributed to two deaths of research
      participants in the United States, clearly also exist in Australia. Health
      research investment in our institutions is large and represents an often
      overlooked area of risk by boards of management. Research governance (the
      framework through which institutions are ultimately accountable for the
      scientific quality, ethical acceptability and safety of research conducted in the
      institutions) has not received sufficient attention. An adequate governance
      framework requires institutions to have policies and procedures in place to meet
      national ethical, legal and research practice standards. We suggest that many
      institutions presently do not have such frameworks in place and inappropriately
      rely too heavily on human research ethics committees. To ensure ongoing adequate
      protection of research participants, we recommend some simple improvements for
      research governance and suggest ways by which institutions can demonstrate
      adherence to agreed national standards.

PMID- 15865593
TI  - Communicating prostate cancer risk: what should we be telling our patients?
AB  - Until definitive evidence of the effectiveness of prostate cancer screening is
      available, most guidelines advocate that men make their own decisions about
      testing, after being fully informed. A man's perception of his personal risk is a
      key element in the decision-making process. In this decision-making, the current
      routine use of population risk estimates may be misleading. Risk estimates need
      to be relevant to the man making the choice. In particular, they should be age
      specific and, where possible, include adjustments for known risk factors such as
      family history. As an example, although the population risk of lung cancer
      mortality is twice that of prostate cancer, for a non-smoking man with a family
      history of prostate cancer the direction of this comparison would be reversed. A
      man aged 50 diagnosed with prostate cancer has a greater likelihood (60%) of
      dying prematurely (before 80 years) from prostate cancer than a man diagnosed
      when aged 70 (38%). This can be attributed to the longer time available for the
      prostate cancer to progress, and the increased effect of competing causes of
      death among older men. This suggests that the oft-used statement "men are more
      likely to die with prostate cancer than from prostate cancer" is misleading,
      particularly for men diagnosed in their 50s or 60s. Decisions need to be made by
      men based on the best possible understanding of their personal vulnerability, and
      the individualisation of risk provides a more realistic appraisal of potential
      threat posed by the disease.

PMID- 15865594
TI  - Venous thromboembolism: diagnosis and management of deep venous thrombosis.
AB  - Venous thromboembolism (VTE) affects 1-2 per 1000 people in the general
      population each year. Clinical diagnosis of deep venous thrombosis (DVT) is
      unreliable, and must be confirmed by compression ultrasonography or venography. A
      low clinical pretest probability of DVT and negative D-dimer result reliably
      exclude the diagnosis, with no need for diagnostic imaging. Initial treatment of
      DVT is with low-molecular-weight heparin or unfractionated heparin for at least 5
      days, followed by warfarin (target INR, 2.0-3.0) for at least 3 months. A vena
      cava filter is indicated in patients who are ineligible for anticoagulant therapy
      or who experience embolism despite therapeutic anticoagulation. Thrombolysis or
      surgical embolectomy may be used as a limb-saving measure in patients with
      extensive proximal DVT and circulatory compromise that threatens the viability of
      the leg. Decisions regarding the optimal duration of anticoagulation to prevent
      recurrent VTE should be individualised and balance the risk of recurrence if
      warfarin is stopped against the risk of major bleeding and inconvenience of
      continuing treatment. The risk of recurrence is highest in people with recurrent
      unprovoked DVT or chronic predisposing factors (eg, cancer) who require
      indefinite anticoagulant treatment.

PMID- 15865595
TI  - Life-threatening allergic bronchopulmonary aspergillosis in a well child with
      cystic fibrosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) is an uncommon condition which may
      complicate asthma and cystic fibrosis; it is seldom considered life-threatening.
      We report a well 8-year-old boy with cystic fibrosis and normal lung function who
      progressed to respiratory failure over several days, attributable to ABPA. He
      recovered with non-invasive ventilation and oral corticosteroid and antifungal
      medications, regaining normal lung function within 2 months. To our knowledge,
      such an acute severe presentation of ABPA in a previously well child has not been
      reported before.

PMID- 15865596
TI  - 9. Common causes of sleep disruption and daytime sleepiness: childhood sleep
      disorders II.
AB  - There are strong associations between childhood sleep disorders and behavioural,
      concentration and mood problems. Sleep disorders caused and maintained by
      behavioural factors (eg, sleep-onset association disorder) are common in young
      children, and have a significant impact on families. Evaluation should include a
      medical history, a physical, neurological and developmental examination, a
      description of any nocturnal events or daytime effects of the child's disturbed
      sleep, and a good understanding of the family situation and parental management
      of the child. Management involves recognising the developmental age of the child
      and the family dynamics, and educating and supporting families in applying
      behavioural techniques to establish good sleep hygiene. Children with parasomnias
      (eg, night terrors) also benefit from good sleep hygiene, while those with
      respiratory or neurological causes of sleep disturbance should be referred for
      specialist treatment.

PMID- 15865597
TI  - Effectiveness and side effects of thiazolidinediones for type 2 diabetes.

PMID- 15865598
TI  - Prevalence of colonisation with vancomycin-resistant enterococci (VRE) among
      haemodialysis outpatients in Victoria: implications for screening.

PMID- 15865599
TI  - Profound hypocalcaemia after zoledronic acid treatment.

PMID- 15865600
TI  - Impact of smoking, diabetes and hypertension on survival in the elderly: the
      Dubbo Study.

PMID- 15865601
TI  - Working with registrars: a registrar's perspective.

PMID- 15865602
TI  - Enhanced laminin binding by alpha-dystroglycan after enzymatic deglycosylation.
AB  - Carbohydrate modifications are clearly important to the function of alpha
      dystroglycan but their composition and structure remain poorly understood. In the
      present study, we describe experiments aimed at identifying the alpha
      dystroglycan oligosaccharides important for its binding to laminin-1 and
      carbohydrate-dependent mAbs (monoclonal antibodies) IIH6 and VIA4(1). We digested
      highly purified skeletal muscle alpha-dystroglycan with an array of linkage
      specific endo- and exoglycosidases, which were verified for action on alpha
      dystroglycan by loss/gain of reactivity for lectins with defined glyco-epitopes.
      Notably, digestion with a combination of Arthrobacter ureafaciens sialidase,
      beta(1-4)galactosidase and beta-N-acetylglucosaminidase substantially degraded
      SiaAalpha2-3Galbeta1-4GlcNAcbeta1-2Man glycans on highly purified alpha
      dystroglycan that nonetheless exhibited enhanced IIH6, VIA4(1) and laminin-1
      binding activity. Additional results indicate that alpha-dystroglycan is probably
      modified with other anionic sugars besides sialic acid and suggest that rare
      alpha-linked GlcNAc moieties may block its complete deglycosylation with
      currently available enzymes.

PMID- 15865603
TI  - Effect of sildenafil and acclimatization on cerebral oxygenation at altitude.
AB  - Phosphodiesterase-5 inhibitors decrease hypoxic pulmonary vasoconstriction under
      hypobaric hypoxia, but are not known to affect cerebral blood flow or
      oxygenation. The present study was designed to evaluate the effect of sildenafil
      on cerebral haemodynamics during acute exposure to altitude and after
      acclimatization. Ten subjects were studied 1 and 3 days after rapid ascent to
      3480 m before and for two consecutive hours after taking sildenafil (50 mg).
      Before acclimatization, HR (heart rate) rose at 1 h (76.3+/-1.0 beats/min
      compared with 72.5+/-1.5 beats/min at baseline; P<0.05) and had returned to
      baseline at 2 h (71.3+/-1.1 beats/min; P>0.05). Mean BP (blood pressure) fell
      from 96.0+/-2.0 mmHg at baseline to 91.7+/-2.5 (P<0.001) at 1 h and 89.8+/-1.8
      mmHg (P<0.0001) at 2 h, whereas SaO2 (arterial oxygen saturation) increased from
      83.9+/-0.5% at baseline to 85.3+/-0.4% (P<0.0001) at 1 h and 85.0+/-0.5% (P<0.01)
      at 2 h. MCAV [MCA (middle cerebral artery) velocity] and PETCO2 (end-tidal
      partial pressure of CO2) were unchanged, but rSO2 (regional cerebral oxygen
      saturation) rose progressively at 1 h (62.7+/-0.8%; P<0.05) and 2 h (65.3+/-0.9%;
      P<0.0001) compared with baseline (59.3+/-1.3%). After 3 days of acclimatization,
      resting rSO2 and RMCA (MCA resistance) increased and oxygen delivery fell.
      Changes in HR and mean BP after sildenafil were similar to day 1, but SaO2 did
      not change. However, rSO2 increased [61.7+/-0.9% at baseline to 65.0+/-1.0%
      (P<0.0001) at 1 h and 64.0+/-0.9% (P<0.001) at 2 h], despite a reduction in MCAV
      [65.3+/-1.8 cm/s at baseline to 61.3+/-1.5 cm/s (P<0.01) at 1 h and 60.9+/-1.7
      cm/s (P<0.0001) at 2 h] and PETCO2 [4.1+/-0.05 kPa at baseline to 4.0+/-0.04 kPa
      at 2 h (P<0.01)]. These observations suggest that sildenafil improves cerebral
      oxygenation at altitude. Whereas the early changes before acclimatization may be
      largely pulmonary in origin, the later observations may be a direct cerebral
      effect which warrants further study.

PMID- 15865604
TI  - Bacterial vaginosis. Transmission, role in genital tract infection and pregnancy
      outcome: an enigma.
AB  - Whether bacterial vaginosis (BV) is acquired from an endogenous or an exogenous
      source is subject to controversy. Despite findings of an association between
      sexual behaviour and BV, some data indicate that BV is not a sexually transmitted
      infection in the traditional sense, while other data indicate that BV is an
      exogenous infection. A third aspect of BV is its tendency to go unnoticed by
      affected women. All of this will have a strong impact on how physicians view the
      risks of asymptomatic BV. This review focuses on whether or not BV should be
      regarded as a sexually transmitted infection (STI), its role in postoperative
      infections and pelvic inflammatory disease (PID), and on whether or not treatment
      of BV during pregnancy to reduce preterm delivery should be recommended. The
      reviewed studies do not lend unequivocal support to an endogenous or exogenous
      transmission of the bacteria present in BV. For women undergoing gynaecological
      surgery such as therapeutic abortion, the relative risk of postoperative
      infection is clearly elevated (approx. 2.3-2.8). A weaker association exists
      between BV and pelvic inflammatory disease. Data on treatment of BV as a way of
      reducing preterm delivery are inconclusive and do not support recommendations for
      general treatment of BV during pregnancy. The discrepant associations between BV
      and preterm birth found in recent studies may be explained by variations in
      immunological response to BV. Genetic polymorphism in the cytokine response--both
      regarding the TNF alleles and in interleukin production--could make women more or
      less susceptible to BV, causing different risks of preterm birth. Thus, studies
      on the vaginal inflammatory response to microbial colonization should be given
      priority.

PMID- 15865605
TI  - The multifunctional role of the immunohistochemical expression of MMP-7 in
      invasive breast cancer.
AB  - The secretion of matrix metalloproteinases (MMPs) is crucial in the metastasis of
      cancer cells, since MMPs are responsible for the degradation of extracellular
      matrix (ECM). Among them, matrix metalloproteinase-7 (MMP-7) or matrilysin 1 is a
      stromelysin which degrades type-IV collagen, fibronectin and laminin.
      Immunohistochemistry was performed to detect MMP-7 protein in infiltrative breast
      carcinomas. MMP-7 was studied along with clinicopathological parameters, disease
      free and overall survival, and p53, c-erbB-2, topoIIa, MMP-2, uPAR and beta
      catenin. MMP-7 immunoreactivity was detected in the cytoplasm of cancer cells in
      54.2% (96/177) and tumor stromal cells in 47.5% (84/177), as well as in normal
      epithelium adjacent to malignant epithelium. MMP-7 reactivity in cancer cells
      displayed an inverse association with nuclear grade (p=0.049) and topoIIa
      (p=0.03). A parallel association was observed between the expression of MMP-7 in
      both malignant and stromal cells with uPAR in cancer cells (p=0.033 and p=0.027,
      respectively). MMP-7 of tumor stromal cells depicted a parallel correlation with
      MMP-2 of the same cell type (p=0.044), while abnormal beta-catenin expression was
      inversely associated with MMP-7 of cancer cells (p=0.047). Our results show the
      multifunctional role of MMP-7 in the mammary gland, since it seems to be
      associated with a less aggressive phenotype, while, at the same time, being
      involved in invasion, through its collaboration with indicators of invasion.

PMID- 15865606
TI  - Effect of monophosphoryl lipid A on antibody response to diphtheria toxin and its
      subunits.
AB  - Monophosphoryl lipid A (MPL) was evaluated for its ability to enhance the
      antibody response to diphtheria toxin and its fragment A and fragment B subunits.
      BALB/c mice were immunized subcutaneously with 1 Lf of diphtheria toxoid in the
      presence of 25 microg of MPL on days 0 and 14. Two weeks after the second
      immunization, sera were obtained from the mice and analysed for antibody response
      to diphtheria toxin and its subunits. A new ELISA method, developed in our
      laboratory, was used to measure antibody levels against the toxin, fragment A,
      and fragment B. It was observed that MPL significantly enhanced antibody
      responses to diphtheria toxin and its subunits. However, there was no statistical
      difference between anti-A and anti-B responses. The results indicated that MPL
      seems to be a potential candidate as an adjuvant for future diphtheria vaccine
      formulation.

PMID- 15865607
TI  - Increased expression of histone deacetylase 2 is found in human gastric cancer.
AB  - Accumulated evidence has established that aberrant regulation of histone
      deacetylases (HDACs) is one of the major causes of the development of human
      malignancies. Among different iso-enzymes of HDAC and sirtuins grouped as the
      HDAC super family, little is known as to how histone deacetylase 2 (HDAC2) causes
      carcinogenesis in solid tumors. Here, in order to investigate the possible role
      of HDAC2 in gastric carcinogenesis, we analyzed the expression of HDAC2 in 71
      gastric adenocarcinomas by immunohistochemistry. Moderate to strong expression of
      HDAC2 was found in 44 (62%) out of a total of 71 tumors. The majority of positive
      tumors, which were detected in the nucleus but not in normal gastric epithelium,
      did not express HDAC2 or showed only weak positive staining. Interestingly, we
      also noted that HDAC2 expression appeared to be associated with tumor
      aggressiveness as HDAC2 expression was observed to be statistically significant
      in advanced gastric cancer (P=0.0023, Chi-square test) and in positive lymph node
      metastasis (P=0.0713, Chi-square test). Taken together, these results suggest
      that HDAC2 may play an important role in the aggressiveness of gastric cancer.

PMID- 15865608
TI  - Intravenous immunoglobulin preparations promote apoptosis in lipopolysaccharide
      stimulated neutrophils via an oxygen-dependent pathway in vitro.
AB  - Since prolonged survival of activated neutrophils has an autotoxic potential,
      neutrophil apoptosis plays an important role in the rapid resolution of
      inflammation. Intravenous immunoglobulin (IVIG) preparations, which are
      beneficial therapeutic agents for the treatment of autoimmune diseases and
      systemic inflammatory diseases, have been reported to induce apoptosis of
      lymphocytes and endothelial cells in vitro. In the present study, we investigated
      whether IVIG may induce apoptosis of neutrophils cultured in vitro. After
      neutrophils prestimulated with or without lipopolysaccharide (LPS) were cultured
      in the presence or absence of IVIG, the number of apoptotic cells, intracellular
      H2O2 and GSH were measured by a flow cytometer. IVIG induced apoptosis of LPS
      stimulated neutrophils dose dependently, but not in unstimulated neutrophils.
      Although anti-Fas monoclonal antibodies (mAbs) had no effect on the IVIG-induced
      apoptosis in the LPS-stimulated neutrophils, anti-Fc gamma receptor (Fc gammaR)
      II- and III-blocking mAbs significantly inhibited the IVIG-induced apoptosis.
      IVIG increased the production of intracellular H2O2, while it decreased the
      production of GSH, in the LPS-stimulated neutrophils. Furthermore, a specific
      NADPH oxidase inhibitor and anti-oxidants inhibited the IVIG-induced neutrophil
      apoptosis. Therefore, these findings indicate that IVIG preparations induce
      apoptosis of LPS-stimulated neutrophils and suggest that the IVIG-induced
      apoptosis may be mediated by an oxygen-dependent pathway via Fc gammaRII and III.

PMID- 15865609
TI  - In vitro susceptibility of yeasts isolated from patients in intensive care units
      to fluconazole and amphotericin B during a 3-year period.
AB  - Fungal infections have increased dramatically in recent years and candidemia is a
      major risk factor for morbidity and mortality in intensive care units (ICUs).
      Candidemia has been considered to be a nosocomial infection that is strongly
      associated with neutropenia, recent surgery or presence of intravascular lines,
      and previous colonization is an independent risk factor. We evaluated the in
      vitro efficacy of fluconazole and amphotericin B against yeasts isolated from
      various clinical specimens of colonized or infected patients treated in the ICUs
      of the Institute of Cardiology, Istanbul University. A total of 1397 ICU patients
      were treated at the Institute of Cardiology between January 2000 and December
      2002. A total of 117 yeasts isolated from 97 patients were included in this
      study. These ICU patients were hospitalized for a mean of 29 days. All yeasts
      were identified by conventional methods and using the API (20C AUX, ID 32C)
      system (Bio Merieux, France). Susceptibility to fluconazole and amphotericin B
      was evaluated using the E-test (AB Biodisk, Solna, Sweden). The most commonly
      isolated yeast was Candida albicans (72.6%), followed by Candida tropicalis
      (16.2%), Candida kefyr, Candida krusei, Candida parapsilosis, Trichosporon
      mucoides and Geotrichum spp. Fluconazole and amphotericin B MIC90 values were
      0.75 microg/ml; 0.19 microg/ml and 1 microg/ml; 0.38 microg/ml for C. albicans
      and C. tropicalis, respectively. All Geotrichum spp. were found to be susceptible
      dose dependent (SDD) (MIC=16-32 microg/ml) to fluconazole. Two C. albicans, two
      C. tropicalis, one C. krusei and one Geotrichum spp. had a MIC value of > or =
      0.38 microg/ml for amphotericin B. The rate of colonization was 3.36% (47/1397).
      Only 10 (0.71%) patients out of a total of 1397 developed candidemia during the
      period of the investigation. Of these, 7 (70%) were caused by non-albicans
      Candida spp.

PMID- 15865610
TI  - Correlation between adjuvanticity and immunogenicity of cholera toxin B subunit
      in orally immunised young chickens.
AB  - The aim of the present study was to investigate whether the adjuvanticity of the
      cholera toxin B (CTB) subunit was correlated with its immunogenicity in young
      orally immunised chickens. Thirteen 15-day-old chickens were orally immunised
      with bovine serum albumin (BSA) glutaraldehyde coupled to CTB. The chicken
      antibody (IgG) concentrations against BSA and CTB, respectively, were quantified
      by ELISA. A significant positive correlation (r=0.66, n=39, p<0.001) between the
      concentrations of immunospecific antibodies with specificities against BSA and
      CTB, respectively, demonstrated that the adjuvanticity of CTB is correlated with
      its immunogenicity.

PMID- 15865611
TI  - Progressive transformation of germinal center presenting with histological
      features of hyaline-vascular type of Castleman's disease.
AB  - We report three cases showing progressive transformation of the germinal center
      (PTGC) with histological features reminiscent of the hyaline-vascular (HV)
      variant of Castleman's disease (CD). Each case contained a few small HV germinal
      centers as well as PTGC and hyperplastic germinal centers with or without
      follicular lysis. Moreover, some of the PTGC were penetrated by hyalinized small
      vessels. Our three cases also showed some of the characteristic histological
      findings of HV type of CD: (i) reactive lymphoid follicles with small hyaline
      vascular germinal centers surrounded by small lymphocytes in a concentrated
      fashion; (ii) a few small foci of plasmacytoid monocytes; (iii) perivascular
      fibrosis; (iv) interfollicular vascularity; (v) tight/concentric pattern of the
      follicular dendritic cell network; and (vi) absence of CD57+ T-cells in the HV
      follicles. The PTGC with coexistent HV type of CD may represent a certain form of
      reactive follicular hyperplasia. The possibility of PTGC should be considered and
      excluded before diagnosing CD.

PMID- 15865612
TI  - Osteogenic melanoma.
AB  - A case of osteogenic melanoma arising in the sole of the foot of a 75-year-old
      male is described. The patient had a history of cutaneous malignant melanoma of
      the left sole from 15 years previously with local recurrence 5 years previously.
      A second recurrence presented as an unencapsulated, poorly circumscribed mass
      measuring 7.5x6x3 cm, located in the dermis, subcutis and muscle, and composed of
      a lobular growth of malignant osteocartilaginous elements with foci of
      epithelioid cells. The tumor was strongly positive for HMB45 and S-100 protein.
      No conventional melanoma was found in the skin. The patient had no evidence of
      recurrence or metastasis 10 months after surgery. Pathologists and clinicians
      should be aware of the existence of osteogenic melanoma and should differentiate
      it from mimics.

PMID- 15865613
TI  - Ovarian ependymoma.
AB  - A 76-year-old woman presented with a large calcifying mass behind the bladder.
      The tumor contained solid areas of a yellowish white color. Microscopic
      examination revealed highly cellular solid areas with many typical ependymal
      perivascular pseudorosettes. The cells contained uniform round-to-oval nuclei,
      some of which had irregular contours, clumped chromatin and occasional prominent
      nucleoli. There was widespread geographic necrosis and there were 5 atypical
      mitotic figures per 10 high power fields. Glial fibrillary acidic protein (GFAP)
      immunopositivity was observed in the cytoplasm of the tumor cells. Based on the
      histopathologic and immunohistochemical features, the tumor was diagnosed as an
      anaplastic ependymoma. This is to the best of our knowledge only the second case
      of anaplastic ependymoma in the medical literature.

PMID- 15865615
TI  - The effects of intervention with local electrostatic air cleaners on airborne
      dust and the health of office employees.
AB  - The aim of this intervention study was to identify any health improvements in the
      upper and lower airways of office workers after the installation of local
      electrostatic air cleaners. Eighty persons with airways symptoms were recruited
      and randomly assigned to an intervention or control group. Half of the air
      cleaners had a non-functioning electrostatic unit. Both participants and field
      researchers were blinded to the group status. Subjective symptoms were recorded
      using a questionnaire, and indexes calculated for general, irritation and skin
      symptoms. Objective respiratory health indicators were recorded, with acoustic
      rhinometry and peak expiratory flow (PEF) meters. In the intervention group there
      was a decrease in mean dust concentration from 65 to 35 microg/m(3), and a
      reduction from 57 to 47 microg/m(3) in the control group (P < 0.05 for difference
      in decline). The reduction was observed for all particles sizes. The irritation
      and general symptom indices decreased in both groups, but there was no
      improvement in the intervention group, compared with the control group. Median
      PEF increased 3 ml/s in the intervention group, and decreased 4 ml/s in the
      control group. The adjusted odds ratio for an increase above the 70th percentile
      was 5.7 (95% CI 1.0-32). PRACTICAL IMPLICATIONS: Electrostatic air cleaners can
      reduce the dust concentration effectively in the office environment. Small,
      medium and large sized particles can be reduced by approximately 50%, relatively
      most effectively for the respirable particles. However, the air cleaners tested
      in this study produced an annoying fan noise. Cleaning efficiency and noise data
      should be given consideration before installation. This experimental field study
      suggests that office workers with airways symptoms may benefit from installation
      of local electrostatic air cleaners.

PMID- 15865616
TI  - (1-->3)-Beta-D-glucans and respiratory health: a review of the scientific
      evidence.
AB  - (1-->3)-Beta-D-glucan are non-allergenic structural cell wall components of most
      fungi that have been suggested to play a causal role in the development of
      respiratory symptoms associated with indoor fungal exposure. This review
      describes the currently available epidemiological literature on health effects of
      (1-->3)-beta-D-glucan, focusing on atopy, airway inflammation and symptoms,
      asthma, and lung function. In addition to population studies, studies in human
      volunteers experimentally exposed to (1-->3)-beta-D-glucan are described as well
      as relevant animal studies. Furthermore, the review discusses exposure assessment
      methods, the potential for exposure control and it concludes with identifying
      research needs. The observational and experimental studies reviewed suggested
      some association between (1-->3)-beta-D-glucan exposure, airway inflammation and
      symptoms, however, results were mixed and specific symptoms and potential
      underlying inflammatory mechanisms associated with exposure could not be
      identified. Large observational studies using well validated exposure assessment
      methods are needed to further our knowledge regarding the potential health
      effects of indoor (1-->3)-beta-D-glucan exposure. PRACTICAL IMPLICATIONS: The
      currently available epidemiological data do not permit conclusions to be drawn
      regarding the presence (or absence) of an association between environmental (1-
      >3)-beta-D-glucan exposure and specific adverse health effects, nor is it clear
      from the currently available evidence which specific immunological mechanisms
      underlie the presumed health effects. More and larger observational studies are
      needed to asses whether (1-->3)-beta-D-glucan exposure plays a significant role
      in respiratory morbidity. In addition, existing methods to assess environmental
      (1-->3)-beta-D-glucan exposure require validation and further development before
      they can be used routinely in large scale epidemiological studies.

PMID- 15865617
TI  - Current asthma and respiratory symptoms among pupils in relation to dietary
      factors and allergens in the school environment.
AB  - The aim was to study asthma and allergy in relation to diet and the school
      environment. Pupils (5-14 years) in eight schools received a questionnaire, 1014
      participated (68%). Settled dust was collected on ALK-filters and analyzed for
      allergens from cat (Fel d 1), dog (Can f 1), horse (Equ cx), house dust mites
      (Der p 1, Der f 1), and cockroach (Bla g 1) by ELISA. In total, 6.8% reported cat
      allergy, 4.8% dog allergy, 7.7% doctor's diagnosed asthma and 5.9% current
      asthma, and 7.8% reported wheeze. Current asthma was less common among those
      consuming more fresh milk (P < 0.05) and fish (P < 0.01). Poly-unsaturated fatty
      acids was associated with more wheeze (P < 0.05), olive oil was associated with
      less doctors' diagnosed asthma (P < 0.05). Totally, 74% of the classrooms had
      mean CO(2) <1000 ppm. The median concentration per gram dust was 860 ng/g Fel d
      1, 750 ng/g Can f 1 and 954 U/g Equ cx. Horse allergen was associated with more
      wheeze (P < 0.05), daytime breathlessness (P < 0.05), current asthma (P < 0.05)
      and atopic sensitization (P < 0.05). Dog allergen was associated with wheeze (P <
      0.05) and daytime breathlessness (P < 0.05). The associations between allergens
      and respiratory symptoms were more pronounced among those consuming margarine,
      not consuming butter, and with a low intake of milk. In conclusion, cat, dog and
      horse allergens in schools could be a risk factor for asthma and atopic
      sensitization, and dietary factors may interact with the allergen exposure.
      PRACTICAL IMPLICATIONS: Previous school studies performed by us in mid-Sweden,
      showed that most classrooms did not fulfill the ventilation standards. In this
      study, most of the classrooms fulfilled the ventilation standard, but despite
      that had widespread allergen contamination. Most previous studies have focused on
      cat allergen, but our study has shown that also dog and horse allergens can be
      risk factors for asthma and allergy in schools. As allergens are transported from
      other environments, mainly the home environment, the main prevention should be to
      minimize transfer of allergens. This could be achieved by reducing contacts with
      furry pets and horses, or using different clothes at home and at school (e.g.
      school uniforms). Increased cleaning in the schools may reduce allergen levels,
      but the efficiency of this measure must be evaluated in further intervention
      studies. Finally, our study supports the view that dietary habits among pupils
      should not be neglected and interaction between dietary factors and indoor
      allergen exposure needs to be further investigated.

PMID- 15865618
TI  - A study on VOC source and sink behavior in porous building materials - analytical
      model development and assessment.
AB  - Building materials can strongly affect indoor air quality. Porous building
      materials are not only sources of indoor air pollutants such as volatile organic
      compounds (VOC) but they are also strong sinks of these pollutants. The knowledge
      of VOC transfer mechanisms in these materials is an important step for
      controlling the indoor VOC concentration levels, and for determining the optimum
      ventilation requirements for acceptable IAQ. This study provides a theoretical
      investigation of primary and secondary VOC source and sink behavior of porous
      building materials. A new analytical model was developed based on the fundamental
      theories of mass transfer mechanisms in porous materials. The proposed model
      considers both primary and secondary source/sink behavior for the first time. The
      former refers to the transfer of gas-phase and/or physically adsorbed VOC, while
      the latter refers to the generation or elimination of VOC within the solid
      because of chemical reactions like oxidation, hydrolysis, chemical adsorption,
      etc. The proposed model was assessed with experimental data, namely emission
      tests of carpets and sorption tests of wood chipboard. It was demonstrated that,
      unlike the existing analytical models, the proposed analytical model could
      simultaneously account for the effect of air velocity on both VOC source as well
      as sink behavior. Case studies were then carried out for secondary VOC source
      behavior. Due to the lack of experimental studies on mechanisms of secondary
      behavior, hypothetical generation functions were implemented. It was demonstrated
      that the proposed analytical model is suitable for describing various mechanisms
      involved in the secondary behavior due to the little limitations imposed on the
      generation/elimination term. When VOC generation takes place at the material-air
      interface, the simulation shows that although the primary emission is not
      affected by air velocity, the secondary emission, however, is clearly affected.
      This behavior agrees with the available experimental findings on secondary
      emissions. PRACTICAL IMPLICATION: The analytical model presented in this paper
      can predict both primary and secondary VOC source (emission) or sink (sorption)
      behavior of porous building materials. Since the model considers diffusion and
      adsorption/desorption within the material, and convection over the material
      surface, the simulation using the model can readily provide the effects of
      material properties and airflow properties on the primary and/or the secondary
      behavior, hence, it can provide a better understanding on the mechanisms. This
      will enable us to keep the indoor VOC concentration within a desirable level.

PMID- 15865619
TI  - Indoor/outdoor relationships for PM2.5 and associated carbonaceous pollutants at
      residential homes in Hong Kong - case study.
AB  - Six residences were selected (two roadside, two urban, and two rural) to evaluate
      the indoor-outdoor characteristics of PM(2.5) (aerodynamic diameter <2.5 microm)
      carbonaceous species in Hong Kong during March and April 2004. Twenty-minute
      averaged indoor and outdoor PM(2.5) concentrations were recorded by DustTrak
      samplers simultaneously at each site for 3 days to examine diurnal variability of
      PM(2.5) mass concentrations and their indoor-to-outdoor (I/O) ratios. Daily (24-h
      average) indoor/outdoor PM(2.5) samples were collected on pre-fired quartz-fiber
      filters with battery-powered portable mini-volume samplers and analyzed for
      organic and elemental carbon (OC, EC) by thermal/optical reflectance (TOR)
      following the Interagency Monitoring of Protected Visual Environments (IMPROVE)
      protocol. The average indoor and outdoor concentrations of 24 h PM(2.5) were 56.7
      and 43.8 microg/m(3), respectively. The short-term PM(2.5) profiles indicated
      that the penetration of outdoor particles was an important contributor to indoor
      PM(2.5), and a household survey indicated that daily activities were also sources
      of episodic peaks in indoor PM(2.5). The average indoor OC and EC concentrations
      of 17.1 and 2.8 microg/m(3), respectively, accounted for an average of 29.5 and
      5.2%, respectively, of indoor PM(2.5) mass. The average indoor OC/EC ratios were
      5.8, 9.1, and 5.0 in roadside, urban, and rural areas, respectively; while
      average outdoor OC/EC ratios were 4.0, 4.3, and 4.0, respectively. The average
      I/O ratios of 24 h PM(2.5), OC, and EC were 1.4, 1.8, and 1.2, respectively. High
      indoor-outdoor correlations (r(2)) were found for PM(2.5) EC (0.96) and mass
      (0.81), and low correlations were found for OC (0.55), indicative of different
      organic carbon sources indoors. A simple model implied that about two-thirds of
      carbonaceous particles in indoor air are originated from outdoor sources.
      PRACTICAL IMPLICATIONS: Indoor particulate pollution has received more attentions
      in Asia. This study presents a case study regarding the fine particulate matter
      and its carbonaceous compositions at six residential homes in Hong Kong. The
      characteristics and relationship of atmospheric organic and elemental carbon were
      discussed indoors and outdoors. The distribution of eight carbon fractions was
      first reported in indoor samples to interpret potential sources of indoor
      carbonaceous particles. The data set can provide significant scientific basis for
      indoor air quality and epidemiology study in Hong Kong and China.

PMID- 15865620
TI  - Field study on occupant comfort and the office thermal environment in rooms with
      displacement ventilation.
AB  - A field survey of occupants' response to the indoor environment in 10 office
      buildings with displacement ventilation was performed. The response of 227
      occupants was analyzed. About 24% of the occupants in the survey complained that
      they were daily bothered by draught, mainly at the lower leg. Vertical air
      temperature difference measured between head and feet levels was less than 3
      degrees C at all workplaces visited. Combined local discomfort because of draught
      and vertical temperature difference does not seem to be a serious problem in
      rooms with displacement ventilation. Almost one half (49%) of the occupants
      reported that they were daily bothered by an uncomfortable room temperature.
      Forty-eight per cent of the occupants were not satisfied with the air quality.
      PRACTICAL IMPLICATIONS: The PMV and the Draught Rating indices as well as the
      specifications for local discomfort because of the separate impact of draught and
      vertical temperature difference, as defined in the present standards, are
      relevant for the design of a thermal environment in rooms with displacement
      ventilation and for its assessment in practice. Increasing the supply air
      temperature in order to counteract draught discomfort is a measure that should be
      considered carefully; even if the desired stratification of pollution in the
      occupied zone is preserved, an increase of the inhaled air temperature may have a
      negative effect on perceived air quality.

PMID- 15865622
TI  - American Geriatrics Society 2005 Annual Scientific Meeting, May 11-15, 2005,
      Orlando, Florida, USA. Abstracts.

PMID- 15865621
TI  - Airborne particle deposition onto the ocular surface.
AB  - Eye irritation is one of the most frequently reported symptoms in relation to
      working in office-like environments. So far, no consistent association has been
      found between concentration of airborne particles and prevalence of eye
      irritation. External physical factors not hitherto considered could have a large
      influence on particle deposition velocity onto the ocular surface. This may have
      obscured the role airborne particles play. Based on previously published semi
      empirical models, the paper describes the influence of turbulence, gravitational
      settling, electrical fields, and thermophoresis on deposition velocity. A
      probabilistic approach was used to determine percentile ranges in deposition
      velocity when the magnitude of these parameters varied within typical ranges. The
      calculations suggest that differences in external factors other than particle
      size may cause differences in the deposition velocity of one order of magnitude
      or more. Studies trying to find associations between airborne particle
      concentration levels and eye irritation should take into consideration the
      influence of external physical factors on deposition velocity. PRACTICAL
      IMPLICATIONS: External physical factors other than concentration are likely to
      have a large influence on the deposition rate of airborne particles onto the
      ocular surface. Thus, future studies on associations between airborne particle
      levels and eye symptoms should only be conducted if particle concentration
      measurements are suitably size resolved. Other relevant external physical factors
      should also be assessed and included in a multivariate analysis of exposure
      response associations.

PMID- 15865623
TI  - Early efficacy of CABG care delivery in a low procedure-volume community
      hospital: operative and midterm results.
AB  - BACKGROUND: The Leapfrog Group recommended that coronary artery bypass grafting
      (CABG) surgery should be done at high volume hospitals (>450 per year) without
      corresponding surgeon-volume criteria. The latter confounds procedure-volume
      effects substantially, and it is suggested that high surgeon-volume (>125 per
      year) rather than hospital-volume may be a more appropriate indicator of CABG
      quality. METHODS: We assessed 3-year isolated CABG morbidity and mortality
      outcomes at a low-volume hospital (LVH: 504 cases) and compared them to the
      corresponding Society of Thoracic Surgeons (STS) national data over the same
      period (2001-2003). All CABGs were performed by 5 high-volume surgeons (161-285
      per year). "Best practice" care at LVH -- including effective practice
      guidelines, protocols, data acquisition capabilities, case review process,
      dedicated facilities and support personnel -- were closely modeled after a high
      volume hospital served by the same surgeon-team. RESULTS: Operative mortality was
      similar for LVH and STS (OM: 2.38% vs. 2.53%), and the corresponding LVH observed
      to-expected mortality (O/E = 0.81) indicated good quality relative to the STS
      risk model (O/E<1). Also, these results were consistent irrespective of risk
      category: O/E was 0, 0.9 and 1.03 for very-low risk (<1%), low risk (1-3%) and
      moderate-to-high risk category (>3%), respectively. Postoperative leg wound
      infections, ventilator hours, renal dysfunction (no dialysis), and atrial
      fibrillation were higher for LVH, but hospital stay was not. The unadjusted
      Kaplan-Meier survival for the LVH cohort was 96%, 94%, and 92% at one, two, and
      three years, respectively. CONCLUSION: Our results demonstrated that high quality
      CABG care can be achieved at LVH programs if 1) served by high volume surgeons
      and 2) patient care procedures similar to those of large programs are
      implemented. This approach may prove a useful paradigm to ensure high quality
      CABG care and early efficacy at low volume institutions that wish to comply with
      the Leapfrog standards.

PMID- 15865624
TI  - General Practitioners' opinions on their practice in mental health and their
      collaboration with mental health professionals.
AB  - BACKGROUND: Common mental health problems are mainly treated in primary care
      settings and collaboration with mental health services is needed. Prior to re
      organisation of the mental health care offer in a geographical area, a study was
      organized: 1) to evaluate GPs' opinions on their day-to-day practice with
      Patients with Mental Health Problems (PMHP) and on relationships with Mental
      Health Professionals (MHPro); 2) to identify factors associated with perceived
      need for collaboration with MHPro and with actual collaboration. METHODS: All GPs
      in the South Yvelines area in France (n = 492) were informed of the
      implementation of a local mental health program. GPs interested in taking part (n
      = 180) were invited to complete a satisfaction questionnaire on their practice in
      the field of Mental Health and to include prospectively all PMHP consultants over
      an 8-day period (n = 1519). For each PMHP, data was collected on demographic and
      clinical profile, and on needs (met v. unmet) for collaboration with MHPro.
      RESULTS: A majority of GPs rated PMHP as requiring more care (83.4%), more time
      (92.3%), more frequent consultations (64.0%) and as being more difficult to refer
      (87.7%) than other patients. A minority of GPs had a satisfactory relationship
      with private psychiatrists (49.5%), public psychiatrists (35%) and social workers
      (27.8%). 53.9% had a less satisfactory relationship with MHPro than with other
      physicians. Needs for collaboration with a MHPro were more often felt in caring
      for PMHP who were young, not in employment, with mental health problems lasting
      for more than one year, with a history of psychiatric hospitalization, and
      showing reluctance to talk of psychological problems and to consult a MHPro.
      Needs for collaboration were more often met among PMHP with past psychiatric
      consultation or hospitalization and when the patient was not reluctant to consult
      a MHPro. Where needs were not met, GP would opt for the classic procedure of
      mental health referral for only 31.3% of their PMHP. CONCLUSION: GPs need
      targeted collaboration with MHPro to support their management of PMHP, whom they
      are willing to care for without systematic referral to specialists as the major
      therapeutic option.

PMID- 15865625
TI  - Ab initio identification of putative human transcription factor binding sites by
      comparative genomics.
AB  - BACKGROUND: Understanding transcriptional regulation of gene expression is one of
      the greatest challenges of modern molecular biology. A central role in this
      mechanism is played by transcription factors, which typically bind to specific,
      short DNA sequence motifs usually located in the upstream region of the regulated
      genes. We discuss here a simple and powerful approach for the ab initio
      identification of these cis-regulatory motifs. The method we present integrates
      several elements: human-mouse comparison, statistical analysis of genomic
      sequences and the concept of coregulation. We apply it to a complete scan of the
      human genome. RESULTS: By using the catalogue of conserved upstream sequences
      collected in the CORG database we construct sets of genes sharing the same
      overrepresented motif (short DNA sequence) in their upstream regions both in
      human and in mouse. We perform this construction for all possible motifs from 5
      to 8 nucleotides in length and then filter the resulting sets looking for two
      types of evidence of coregulation: first, we analyze the Gene Ontology annotation
      of the genes in the set, searching for statistically significant common
      annotations; second, we analyze the expression profiles of the genes in the set
      as measured by microarray experiments, searching for evidence of coexpression.
      The sets which pass one or both filters are conjectured to contain a significant
      fraction of coregulated genes, and the upstream motifs characterizing the sets
      are thus good candidates to be the binding sites of the TF's involved in such
      regulation. In this way we find various known motifs and also some new candidate
      binding sites. CONCLUSION: We have discussed a new integrated algorithm for the
      "ab initio" identification of transcription factor binding sites in the human
      genome. The method is based on three ingredients: comparative genomics,
      overrepresentation, different types of coregulation. The method is applied to a
      full-scan of the human genome, giving satisfactory results.

PMID- 15865626
TI  - Co-release of noradrenaline and dopamine in the cerebral cortex elicited by
      single train and repeated train stimulation of the locus coeruleus.
AB  - BACKGROUND: Previous studies by our group suggest that extracellular dopamine
      (DA) and noradrenaline (NA) may be co-released from noradrenergic nerve terminals
      in the cerebral cortex. We recently demonstrated that the concomitant release of
      DA and NA could be elicited in the cerebral cortex by electrical stimulation of
      the locus coeruleus (LC). This study analyses the effect of both single train and
      repeated electrical stimulation of LC on NA and DA release in the medial
      prefrontal cortex (mPFC), occipital cortex (Occ), and caudate nucleus. To rule
      out possible stressful effects of electrical stimulation, experiments were
      performed on chloral hydrate anaesthetised rats. RESULTS: Twenty min electrical
      stimulation of the LC, with burst type pattern of pulses, increased NA and DA
      both in the mPFC and in the Occ. NA in both cortices and DA in the mPFC returned
      to baseline within 20 min after the end of the stimulation period, while DA in
      the Occ reached a maximum increase during 20 min post-stimulation and remained
      higher than baseline values at 220 min post-stimulation. Local perfusion with
      tetrodotoxin (TTX, 10 microM) markedly reduced baseline NA and DA in the mPFC and
      Occ and totally suppressed the effect of electrical stimulation in both areas. A
      sequence of five 20 min stimulations at 20 min intervals were delivered to the
      LC. Each stimulus increased NA to the same extent and duration as the first
      stimulus, whereas DA remained elevated at the time next stimulus was delivered,
      so that baseline DA progressively increased in the mPFC and Occ to reach about
      130 and 200% the initial level, respectively. In the presence of the NA transport
      (NAT) blocker desipramine (DMI, 100 microM), multiple LC stimulation still
      increased extracellular NA and DA levels. Electrical stimulation of the LC
      increased NA levels in the homolateral caudate nucleus, but failed to modify DA
      level. CONCLUSION: The results confirm and extend that LC stimulation induces a
      concomitant release of DA and NA in the mPFC and Occ. The different time-course
      of LC-induced elevation of DA and NA suggests that their co-release may be
      differentially controlled.

PMID- 15865627
TI  - The risk of menstrual abnormalities after tubal sterilization: a case control
      study.
AB  - BACKGROUND: Tubal sterilization is the method of family planning most commonly
      used. The existence of the post-tubal-ligation syndrome of menstrual
      abnormalities has been the subject of debate for decades. METHODS: In a cross
      sectional study, 112 women with the history of Pomeroy type of tubal ligation
      achieved by minilaparatomy as the case group and 288 women with no previous tubal
      ligation as the control group were assessed for menstrual abnormalities. RESULTS:
      Menstrual abnormalities were not significantly different between the case and
      control groups (p = 0.824). The abnormal uterine bleeding frequency differences
      in two different age groups (30-39 and 40-45 years old) were statistically
      significant (p = 0.0176). CONCLUSION: Tubal sterilization does not cause
      menstrual irregularities.

PMID- 15865628
TI  - Sickle cell disease.

PMID- 15865629
TI  - Acute myocardial infarction.

PMID- 15865632
TI  - Cardiovascular disorders. Changing behaviour.

PMID- 15865633
TI  - Heart failure.

PMID- 15865634
TI  - Peripheral arterial disease.

PMID- 15865638
TI  - Stroke prevention.

PMID- 15865639
TI  - Thromboembolism.

PMID- 15865640
TI  - Varicose veins.

PMID- 15865644
TI  - Bronchiolitis.

PMID- 15865645
TI  - Cardiorespiratory arrest in children.

PMID- 15865647
TI  - Croup.

PMID- 15865648
TI  - Depression in children and adolescents.

PMID- 15865649
TI  - Gastroenteritis in children.

PMID- 15865654
TI  - Neonatal jaundice.

PMID- 15865656
TI  - Nosebleeds in children.

PMID- 15865657
TI  - Perinatal asphyxia.

PMID- 15865659
TI  - Sudden infant death syndrome.

PMID- 15865661
TI  - Acute cholecystitis.

PMID- 15865662
TI  - Anal fissure (chronic).

PMID- 15865664
TI  - Colonic diverticular disease.

PMID- 15865665
TI  - Constipation in adults.

PMID- 15865667
TI  - Helicobacter pylori infection.

PMID- 15865668
TI  - Inguinal hernia.

PMID- 15865669
TI  - Irritable bowel syndrome.

PMID- 15865671
TI  - Stomach cancer.

PMID- 15865672
TI  - Chronic suppurative otitis media.

PMID- 15865673
TI  - Ear wax.

PMID- 15865674
TI  - Meniere's disease.

PMID- 15865676
TI  - Otitis externa.

PMID- 15865677
TI  - Otitis media with effusion.

PMID- 15865680
TI  - Tinnitus.

PMID- 15865681
TI  - Tonsillitis.

PMID- 15865682
TI  - Diabetic nephropathy.

PMID- 15865687
TI  - Primary hypothyroidism.

PMID- 15865688
TI  - Acute anterior uveitis.

PMID- 15865690
TI  - Bacterial conjunctivitis.

PMID- 15865691
TI  - Cataract.

PMID- 15865692
TI  - Diabetic retinopathy.

PMID- 15865700
TI  - Amoebic dysentery.

PMID- 15865701
TI  - Chickenpox.

PMID- 15865702
TI  - Congenital toxoplasmosis.

PMID- 15865703
TI  - Dengue fever.

PMID- 15865706
TI  - Influenza.

PMID- 15865707
TI  - Leprosy.

PMID- 15865708
TI  - Lyme disease.

PMID- 15865709
TI  - Malaria: prevention in travellers.

PMID- 15865710
TI  - Malaria: severe, life threatening.

PMID- 15865711
TI  - Meningococcal disease.

PMID- 15865712
TI  - Postherpetic neuralgia.

PMID- 15865716
TI  - Chronic prostatitis.

PMID- 15865719
TI  - Varicocele.

PMID- 15865722
TI  - Bulimia nervosa.

PMID- 15865723
TI  - Deliberate self harm.

PMID- 15865724
TI  - Dementia.

PMID- 15865725
TI  - Depressive disorders.

PMID- 15865726
TI  - Generalised anxiety disorder.

PMID- 15865730
TI  - Schizophrenia.

PMID- 15865733
TI  - Carpal tunnel syndrome.

PMID- 15865734
TI  - Chronic fatigue syndrome.

PMID- 15865738
TI  - Leg cramps.

PMID- 15865739
TI  - Low back pain (acute).

PMID- 15865740
TI  - Low back pain (chronic).

PMID- 15865742
TI  - Musculoskeletal disorders. Non-steroidal anti-inflammatory drugs.

PMID- 15865744
TI  - Raynaud's phenomenon (primary).

PMID- 15865747
TI  - Altitude sickness.

PMID- 15865753
TI  - Multiple sclerosis.

PMID- 15865755
TI  - Trigeminal neuralgia.

PMID- 15865757
TI  - Burning mouth syndrome.

PMID- 15865758
TI  - Candidiasis (oropharyngeal).

PMID- 15865759
TI  - Halitosis.

PMID- 15865761
TI  - Postoperative pulmonary infections.

PMID- 15865762
TI  - Organophosphorus poisoning (acute).

PMID- 15865763
TI  - Paracetamol (acetaminophen) poisoning.

PMID- 15865767
TI  - Postnatal depression.

PMID- 15865768
TI  - Pre-eclampsia and hypertension.

PMID- 15865772
TI  - Sore throat.

PMID- 15865780
TI  - Chlamydia (uncomplicated, genital).

PMID- 15865786
TI  - Athlete's foot.

PMID- 15865787
TI  - Cellulitis and erysipelas.

PMID- 15865790
TI  - Herpes labialis.

PMID- 15865791
TI  - Malignant melanoma (non-metastatic).

PMID- 15865793
TI  - Seborrhoeic dermatitis.

PMID- 15865794
TI  - Squamous cell carcinoma of the skin (non-metastatic).

PMID- 15865796
TI  - Wrinkles.

PMID- 15865797
TI  - Insomnia.

PMID- 15865798
TI  - Jet lag.

PMID- 15865799
TI  - Sleep apnoea.

PMID- 15865803
TI  - Candidiasis (vulvovaginal).

PMID- 15865804
TI  - Domestic violence towards women.

PMID- 15865805
TI  - Dysmenorrhoea.

PMID- 15865807
TI  - Fibroids (uterine myomatosis, leiomyomas).

PMID- 15865808
TI  - Genital prolapse.

PMID- 15865811
TI  - Menorrhagia.

PMID- 15865817
TI  - Stress incontinence.

PMID- 15865813
TI  - Polycystic ovary syndrome.

PMID- 15865818
TI  - Bites (mammalian).

PMID- 15865819
TI  - Minor thermal burns.

PMID- 15865821
TI  - Venous leg ulcers.

PMID- 15865824
TI  - Assessment of operability for common arterial trunk without cardiac
      catheterisation.
AB  - Pulmonary vascular disease is a risk factor for the surgical management of common
      arterial trunk. Surgical repair, therefore, is usually performed in early
      infancy, before irreversible changes can occur in the epulmonary vasculature.
      Because of this, there has been an increasing tendency to dispense with cardiac
      catheterisation as a means of assessing pulmonary vascular disease. Cardiac
      catheterisation, nonetheless, is still performed when there is a risk of
      pulmonary vascular disease, such as in older children. There are no clear
      guidelines, however, as to who should be catheterised. We have developed a simple
      screening test to help make this decision.

PMID- 15865825
TI  - Mid-term effects of implanting stents for relief of aortic recoarctation on
      systemic hypertension, carotid mechanical properties, intimal medial thickness
      and reflection of the pulse wave.
AB  - OBJECTIVE: Primary implantation of stents is an accepted technique for treating
      aortic recoarctation, albeit that the effects of stenting on pressure profiles,
      carotid mechanical properties, intimal medial thickness, and reflection of the
      pulse wave have not been systematically investigated. METHODS: Over the period
      from 1 January, 1999, to 31 December, 2002, we implanted stents to relieve aortic
      recoarctation in 15 patients, with a median age of 17 years, and a range from 7
      to 29 years, with a median weight of 56 kilograms, ranging from 20 to 96
      kilograms. Indications were a gradient of 20 millimetres of mercury or more
      measured in all, systemic hypertension at rest in 8, and systemic hypertension at
      exercise in all. Of the patients, 5 were receiving anti-hypertensive treatment.
      Before implantation of the stents, and after a mean follow-up of 22 months, all
      patients underwent an exercise test, vascular echography, and examination of the
      common carotid artery so as to determine its cross sectional compliance and
      distensibility, and the augmentation index. results: The stents were implanted
      successfully in all patients. The mean gradient was reduced from 27 to 4
      millimetres of mercury (p < 0.001). Systolic blood pressure at rest diminished
      from 140 to 131 millimetres of mercury (p = 0.04), while hypertension at rest
      regressed in 4 patients. Systolic blood pressure at exercise diminished from 245
      to 222 millimetres of mercury (p = 0.018), and hypertension at exercise regressed
      in 1 patient. Anti-hypertensive treatment is still required for 4 patients. A
      correlation was found between systolic blood pressure at rest and initial peak-to
      peak gradient (r = 0.8), and between initial gradient and percentage reduction of
      systolic blood pressure at rest at follow-up (r = -0.73). Compliance and
      distensibility of the common carotid artery were not significantly modified,
      albeit that the intimal medial thickness diminished from 0.64 to 0.57 millimetres
      (p = 0.04), and the augmentation index decreased from 5 to -1 (p = 0.012).
      CONCLUSIONS: Primary implantation of stents is effective in mid-term repair of
      aortic recoarctation. Although there is an improvement in systemic hypertension,
      the tensional profile and vascular sonography are not normalized. At long term
      follow-up, the suppression of an early reflection site of the pulse wave could
      decrease the wall stress of the great elastic vessels, reducing the thickness of
      the arterial walls.

PMID- 15865826
TI  - The potential impact of prophylaxis against bronchiolitis due to the respiratory
      syncytial virus in children with congenital cardiac malformations.
AB  - AIMS: To determine the number of infants in the Mersey and North West regions
      with congenital cardiac disease for whom palivizumab may be appropriate, and to
      examine the potential impact of introducing prophylaxis with palivizumab on these
      patients and their economic management. METHODS: We identified those infants
      deemed to be at high risk, matching the population recently studied by the
      Cardiac Synagis Group, from the database of the cardiology department of the
      hospital. The number of patients under the care of the paediatric cardiologists
      admitted to Alder Hey Hospital with respiratory syncytial viral bronchiolitis
      over the last three seasons was identified from hospital coding records, and the
      database of the cardiology department. RESULTS: There are 131 patients at high
      risk each year. Of these, over the last three "bronchiolitis seasons", 39 infants
      have been admitted to the hospital with bronchiolitis due to the respiratory
      syncytial virus. This represents a hospitalisation rate of 10 per cent, as was
      seen in the study of the Cardiac Synagis Group. Using a monthly dose of 15
      milligrams per kilogram for five doses, the cost per patient is 2,650 pounds
      sterling for the season. To treat the 131 patients seen at Alder Hey, therefore,
      would cost 346,800 pounds each year. Applying the reductions in hospitalisation
      identified in the study by the Cardiac Synagis Group to our population would
      produce an expected reduction in patients hospitalised from 13 to 7 per year,
      reducing the total length of stay in our hospital wards from 169 to 76 days, and
      in the paediatric intensive care unit from 93 to 21 days. This amounts to a
      potential saving of 190,800 pounds per year. Reducing transfers to more distant
      paediatric intensive care units for referrals refused because of lack of beds
      could save an additional 50,000 pounds. DISCUSSION: We estimate the net cost of
      introducing palivizumab for this population to be 106,000 pounds per year. There
      would, of course, be additional costs involved in setting up this service, as
      well as additional savings and benefits. This cost is comparable with other new
      biologic therapies now routinely used in the United Kingdom, such as etanercept
      for juvenile arthritis. There are, currently, no other obvious therapies that
      have the potential to reduce admissions to hospital and intensive care during the
      winter months, when beds are at their most scarce.

PMID- 15865827
TI  - Infection by the respiratory syncytial virus in infants and young children at
      high risk.
AB  - The respiratory syncytial virus is the most common cause of infection of the
      lower respiratory tract in infants and young children, and is the leading cause
      of hospitalisation and death due to viral illness during the first year of life.
      In otherwise healthy infants, the virus usually causes only mild respiratory
      illness, but premature babies and infants with chronic lung disease, those with
      congenitally malformed hearts, or those who are immunodeficient, are at increased
      risk of serious illness, hospitalisation, and death. Recent infection with the
      virus is also associated with increased postoperative complications after
      corrective surgery for congenitally malformed hearts. No effective vaccine is
      currently available, and treatment is limited to supportive therapy. Prevention
      in groups deemed to be at high-risk, therefore, is essential. In addition to
      measures for control of infection, prophylactic immunotherapy is indicated in
      selected patients. Palivizumab (Synagis) is a monoclonal antibody indicated for
      the prevention of serious viral disease of the lower respiratory tract in
      premature infants, those with chronic lung disease, and those with
      haemodynamically significant congenital cardiac lesions. Palivizumab is given
      intramuscularly, usually as a monthly injection during the so-called "season". In
      a recent international, randomised, double-blind, placebo-controlled trial in
      1,287 children less than or equal to 2 years old with haemodynamically
      significant congenital cardiac malformations, prophylaxis achieved a relative
      reduction of 45 per cent in the incidence of antigen-confirmed viral-related
      hospitalisation, and reduced the duration of hospital stay by 56 per cent.
      National and international guidelines, therefore, now recommend routine
      prophylaxis in the first year of life in children with haemodynamically
      significant congenital cardiac disease.

PMID- 15865828
TI  - Acute and long-term effects of infection by the respiratory syncytial virus in
      children with congenital cardiac malformations.
AB  - All newborn infants have limited pulmonary reserve compared with older children.
      This puts them at increased risk of respiratory complications, such as those
      associated with infection by the respiratory syncytial virus. Young children with
      congenital cardiac disease are particularly likely to suffer severe disease
      related to infection by the virus. In these children, the extreme vulnerability
      of the lung to pulmonary oedema is compounded by the additional burden caused by
      the respiratory syncytial virus. In addition to the well-documented acute
      pulmonary effects of infection with the respiratory syncytial virus, there may
      also be consequent long-term respiratory morbidity. Clinical studies have shown
      that infection by the virus in infancy is associated with a higher risk of
      developing subsequent bronchial obstructive disease. Much debate surrounds the
      mechanisms underlying this association. It is thought that a combined
      immunological and neurogenic response mechanism is likely. Prevention of severe
      respiratory disease in infants and young children with congenital heart disease
      due to infection by the virus may, therefore, offer both immediate and long-term
      benefits. Indeed, an increasing body of evidence supports this hypothesis,
      indicating a clinical rationale for prophylaxis against the virus in infancy, in
      order to reduce the chance of developing reactive airways disease and asthma in
      later life.

PMID- 15865829
TI  - The European Forum for Clinical Management: prophylaxis against the respiratory
      syncytial virus in infants and young children with congenital cardiac disease.
AB  - A recent, randomised, double-blind, placebo-controlled trial has demonstrated the
      effectiveness of palivizumab (Synagis) for prophylaxis against infection by the
      respiratory syncytial virus in 1,287 young children with congenital cardiac
      disease. Guidelines for the use of palivizumab in these children considered to be
      at high risk were published by the American Academy of Pediatrics, followed by
      similar guidelines from the British Paediatric Cardiac Association, and
      recommendations from a number of other individual countries, including Canada,
      Germany, Spain, and France. In May, 2004, further discussion was held between a
      group of 15 paediatric cardiologists at a European forum for clinical management
      held in Munich, Germany. The objective of this forum was to define optimal
      recommendations on prevention of infection by the respiratory syncytial virus in
      infants and young children with congenital cardiac disease, appropriate to the
      clinical needs and style of those practising in paediatrics in individual
      countries. Participants were invited because of their knowledge of the
      therapeutic area, and for their experience of using palivizumab for prophylaxis
      against the respiratory syncytial virus in children with congenitally malformed
      hearts. Measures to educate the carers of children with such congenital
      malformations on precautions against infection by the respiratory syncytial virus
      were discussed, along with the many different aspects of best practice for
      therapeutic prophylaxis with palivizumab. The most appropriate timing of
      prophylaxis, recommendations for which children are most likely to benefit from
      prophylaxis, and suggested protocols were among the issues covered. The
      recommendations resulting from the discussions are presented in this paper, as a
      step towards reaching consensus.

PMID- 15865830
TI  - The efficacy and safety of the Amplatzer ductal occluder in young children and
      infants.
AB  - BACKGROUND: We have used the Amplatzer ductal occluder for transcatheter closure
      of large persistently patent arterial ducts, and used our experience to assess
      the safety and efficacy of the device in young children and infants. METHODS AND
      PATIENTS: We used the Amplatzer ductal occluder prospectively in 43 patients with
      large patent arterial ducts, reviewing our experience to identify any problems or
      complications. RESULTS: The procedure proved successful in 42 of the patients. We
      achieved complete occlusion of the duct in 33 (78.5 per cent) of the patients on
      the day of insertion. In 6 additional patients, complete occlusion occurred 1
      week to 6 months after the procedure. Trivial leaks persisted in 2 patients,
      while one had a significant residual leak. Problems were encountered in 7
      patients. The procedure failed in one, a device was wasted in 2, pulled through
      in 3, while we experienced kinking of the long Mullins sheath, being unable to
      retrieve the device, in one patient. Minor complications occurred in 6 patients,
      finding flow at a peak velocity of 2.2 metres per second in the descending aorta
      in 2 patients, and at 2.5 metres per second in 2 further patients, and flow at
      2.5 metres per second in the pulmonary arteries of two patients. One patient
      experienced a major complication due to excessive bleeding. Out of the 14
      patients suffering adverse events, 13 weighed less than 10 kilograms. This rate
      of problems and complication in these patients weighing less than 10 kilograms
      was significantly higher than in the patients weighing more than 10 kilograms.
      CONCLUSION: Transcatheter occlusion of moderate to large patent arterial ducts
      with the Amplatzer ductal occluder device is safe and effective, with a high rate
      of complete occlusion. Problems and minor complications may be encountered in
      children weighing less than 10 kilograms. If the device is to be deployed
      completely in the ductal ampulla, and to avoid descending aortic obstruction, the
      size of the retention flanges of the occluder should not exceed the largest
      diameter of the patent arterial duct.

PMID- 15865831
TI  - Congenital cardiac disease in children with Down's syndrome in Guatemala.
AB  - BACKGROUND: Congenital cardiac disease is the greatest cause of death in patients
      with Down's syndrome during the first two years of life, with from two-fifths to
      two-thirds of those with Down's syndrome also having congenital cardiac
      malformations. The lesions within the heart can be single or multiple. Our
      objective was to evaluate the frequency and type of such congenital cardiac
      malformations in patients born with Down's in Guatemala, and to provide baseline
      information for further research. METHODS: We reviewed all patients with Down's
      syndrome who underwent a cardiologic screening examination between January, 1997,
      and December, 2003, in the only department dealing with Paediatric Cardiology in
      Guatemala. RESULTS: Of the 349 patients reviewed, 189 (54.1 per cent) also had an
      associated congenital cardiac malformation. The median age at diagnosis was 6
      months, with a range from 2 to 13 months. In 152 patients (80.4 per cent), the
      cardiac lesion was isolated, while 37 patients (19.6 per cent) had multiple
      defects. The most common single defect was patency of the arterial duct, found in
      54 of the 189 patients (28.6 per cent), followed by ventricular septal defect in
      27.5 per cent, atrial septal defect in 12.7 per cent, and atrioventricular septal
      defect with common atrioventricular junction in 9.5 per cent. The most frequent
      concomitant malformation found co-existing with other congenital cardiac lesions
      was patency of the arterial duct, found in 17.5 per cent. CONCLUSIONS: As far as
      we are aware, ours is the first epidemiologic study concerning the frequency and
      type of congenital cardiac disease found in Guatemalan children with Down's
      syndrome. The high frequency of patency of the arterial duct, and the
      differential distribution of the cardiac malformations associated with Down's
      syndrome among Guatemalan children, differ from what has been reported in the
      United States of America, Europe, and Asia. This difference warrants further
      research.

PMID- 15865832
TI  - Data from the StEP TWO programme showing the effect on blood pressure and
      different parameters for obesity in overweight and obese primary school children.
AB  - Obesity in childhood, which is associated with cardiovascular risk factors such
      as hypertension, is on the increase. Countermeasures are necessary. In this
      paper, we present the baseline and final data from the StEP TWO programme, a
      prospective study to prevent overweight and obesity in primary schools. METHODS:
      We recorded and calculated, from 1689 children, anthropometric data, including
      analyses of bioelectric impedance, waist and hip circumferences, body mass index
      and its standard deviation, and the ratio of waist to hip. Blood pressure was
      measured after 5 minutes at rest. From the three schools involved in a programme
      of intervention, 121 children were invited to take part, and 40 (33.1 per cent)
      completed the programme. The effect was compared with 155 overweight and obese
      children identified at the 4 control schools. RESULTS: 830 (49.5 per cent) boys
      and 848 girls (50.5 per cent) took part. Their mean age was 8.2 plus or minus 1.3
      years, their height was 1.31 plus or minus 0.09 metres, they weighed 30.0 plus or
      minus 8.2 kilograms, and their mean index of body mass was 17.1 plus or minus 2.9
      kilograms per metre squared. Of the children, 7.3 per cent were obese, 10.4 per
      cent were overweight, 75.7 per cent had normal weights, and 6.6 per cent were
      underweight. Resting hypertension was observed in 2.3 per cent of the children.
      Increased blood pressure was associated with a higher body weight, body mass
      index, standard deviation score for body mass index, and waist and hip
      circumferences (each p < 0.001), but not with the ratio of waist to hip.
      Hypertension at rest was also found in 11.0 per cent of obese children, 4.4 per
      cent of those who were overweight, 1.2 per cent of those with normal weight, and
      1.0 per cent of underweight children (p < 0.001). After the intervention, the
      increase of the body mass index tended to be lower in those in whom we had
      intervened (p = 0.069), and in these the decrease of the standard deviation score
      for body mass index was significantly higher (p = 0.028). Systolic blood pressure
      was reduced by about 10 millimetres of mercury in those in whom we had intervened
      (p = 0.002), while there were no changes in the control group. Diastolic blood
      pressure was lowered by 3 millimetres of mercury, but this was not significant.
      CONCLUSION: Obese children had the highest values for systolic and diastolic
      blood pressure. Increased levels of blood pressure are associated with other
      parameters of obesity, such as the circumference of the waist and hip. Early
      preventive measurements in childhood are necessary, and appropriate intervention
      appears to be effective.

PMID- 15865833
TI  - Development of a cardiac technician led paediatric echocardiographic service-
      experience from a district general hospital in the United Kingdom.
AB  - OBJECTIVES: To report our experience in providing cardiac technician led
      paediatric echocardiography services in a district general hospital in the United
      Kingdom. METHODS: We have collected prospectively the numbers of referrals, and
      the proportion of abnormal echocardiograms, since inception of the service in
      2000. In additional, for a period of 12 months, we have audited in detail the
      patterns of referral to the service, and outcomes, assessing the effect of the
      service on the outreach clinic run by a visiting paediatric cardiologist.
      RESULTS: Use of the system resulted in detection of a wide range of
      abnormalities, with our audit showing that the patients received appropriate
      management. The total referrals to the service increased 10 fold over the 4 year
      period of the study. The proportion of abnormal hearts detected by
      echocardiography, however, dropped from 90 per cent to 16 per cent over the same
      period. The numbers of patients seen in the outreach cardiology clinic remained
      unaltered. CONCLUSIONS: Having been proved to be an effective model for the
      triage of children with suspected congenital cardiac disease, adoption of a
      cardiac technician led echocardiographic service has seen a dramatic increase in
      the numbers of echocardiograms requested, without decreasing the workload of the
      visiting paediatric cardiologist.

PMID- 15865834
TI  - Delineation of unilateral pulmonary hypertensive arteriopathy in a patient with
      Potts shunt using magnetic resonance imaging.

PMID- 15865835
TI  - Totally anomalous pulmonary venous return.

PMID- 15865836
TI  - Congenital right atrial diverticulum, atrial septal defect within the oval fossa,
      and complex pulmonary valvar obstruction in an infant with chromosome 8(p23.1)
      deletion.
AB  - We describe an unusual right atrial aneurysm, occurring with progressive
      obstruction of the right ventricular outflow tract and increasing cyanosis, in a
      nine-month-old boy with chromosome 8(p23.1) deletion. Surgical resection of the
      diverticulum, and relief of the right ventricular obstruction, was successful,
      although impairment of right ventricular compliance persists after 19 months
      follow-up.

PMID- 15865837
TI  - A case of long QT syndrome associated with familial occurrence of persistent
      patency of the arterial duct.
AB  - We describe an occurrence of long QT syndrome in association with persistent
      patency of the arterial duct in members of a family. Patency of the arterial duct
      was diagnosed in family members of 4 successive generations. The index case had
      long QT syndrome associated with such a patent duct. Another patient had long QT
      syndrome, but associated with a ventricular septal defect. We postulate that
      there may be a common genetic mechanism for long QT syndrome and persistent
      patency of the arterial duct.

PMID- 15865838
TI  - Rapid progression of long-segment coarctation in a patient with Williams'
      syndrome.
AB  - Over a period of 6 days, a three-week-old male developed a long-segment
      coarctation, with sub-total obstruction of the descending aorta, immediately
      distal to the left subclavian artery. On the 24th day of life, the stenotic
      region was repaired by placement of a pulmonary allograft patch measuring 3
      centimetres in length. Severe diffuse vascular medial thickening was discovered
      at the operation. Subsequent fluorescence in-situ hybridization proved positive
      for Williams' syndrome. To our knowledge, this is the first report of rapidly
      progressive infantile arteriopathy in the setting of Williams' syndrome.

PMID- 15865839
TI  - Slow and wide QRS complex tachycardia as a unique complication following
      radiofrequency catheter ablation of a left-sided accessory pathway in a child.
AB  - Radiofrequency lesions can, theoretically, be the substrate for new persistent
      arrhythmias. As far as we know, this has never previously been encountered after
      transcatheter ablation of accessory pathways. A child with Wolff-Parkinson-White
      syndrome was referred for radiofrequency catheter ablation of a left-sided
      accessory pathway. After successful ablation of the accessory pathway using a
      retrograde transaortic approach, the child developed an incessant wide QRS
      complex tachycardia at slow rate that was resistant to pharmacologic
      interventions. The focus of the tachycardia was identical to the ventricular site
      of insertion of the eliminated accessory pathway.

PMID- 15865840
TI  - Ventricular tachycardia secondary to prolongation of the QT interval in a fetus
      with autoimmune mediated congenital complete heart block.
AB  - We report a case where fetal echocardiography identified both complete heart
      block and ventricular tachycardia. The mother tested positive for anti-Ro
      antibodies. Prenatal detection of this unusual combination of arrhythmias
      prompted early postnatal evaluation, which revealed prolongation of the QT
      interval. Autoimmune mediated congenitally complete heart block associated with
      such prolongation of the QT interval has a poor prognosis. The child was
      successfully treated with beta blockers and implantation of a pacemaker.

PMID- 15865841
TI  - Idiopathic aneurysm of the inferior caval vein.
AB  - Idiopathic aneurysms of the inferior caval vein are uncommon in children and
      adults. We describe a 14 year old boy with a saccular aneurysm of the inferior
      caval vein, in whom no surgical intervention was required to repair the aneurysm.
      The patient is being followed-up periodically for the evaluation of any increase
      in the diameter of the inferior caval vein.

PMID- 15865842
TI  - A rare complication of the use of the 6 French suture-mediated closure device.

PMID- 15865846
TI  - Role of fulvestrant in sequential hormonal therapy for advanced, hormone receptor
      positive breast cancer in postmenopausal women.
AB  - The introduction of antiendocrine agents with differing mechanisms of action now
      mandates the design of rational sequential hormonal regimens for breast cancer.
      The aromatase inhibitors (AIs), including the nonsteroidal compounds anastrozole
      and letrozole and the steroidal compound exemestane, are important alternatives
      or adjuncts to the antiestrogen agent tamoxifen in postmenopausal women with
      hormone receptor-positive breast cancer in the first-line management of advanced
      disease and in the adjuvant treatment of early-stage disease. These and other
      endocrine agents, including the newer estrogen receptor antagonist fulvestrant
      and also tamoxifen itself, have not been extensively evaluated within the context
      of hormonal sequencing. Based on a retrospective analysis of data from 3 phase
      III trials, patients treated with fulvestrant in the first- or second-line
      hormonal management of advanced breast cancer may derive further clinical benefit
      from subsequent treatment with an endocrine agent from another class. The need
      for prospective investigation of post-AI hormonal therapy is intensifying as a
      result of the increasing clinical use of the AIs. Sophisticated sequencing
      regimens designed to exploit different mechanisms of action have the potential to
      confer greater clinical benefit than the historical approach of selecting the
      agent with the next highest single-agent clinical activity upon disease
      progression.

PMID- 15865847
TI  - Current and future perspectives on fulvestrant.
AB  - Fulvestrant, an estrogen receptor antagonist with no known agonist effects, is
      effective and well tolerated in the treatment of hormone-sensitive breast cancer
      after antiestrogen failure in postmenopausal women. Numerous phase II and III
      clinical trials of fulvestrant that are designed to build on its efficacy in
      breast cancer and explore its value in other tumors are ongoing or in the final
      planning stage. Favorable safety, dose-response, and pharmacokinetic data led to
      the initiation of clinical trials to evaluate loading and higher doses with the
      aim of building on the well-defined efficacy of fulvestrant. Recently reported
      results of phase II trials by the North Central Cancer Treatment Group and the
      Swiss Group for Clinical Cancer Research support the clinical activity of
      fulvestrant after recurrence or progression on a nonsteroidal aromatase
      inhibitor, and 2 international phase III trials are ongoing in this setting. As a
      first-line treatment for metastatic disease, fulvestrant is currently being
      evaluated in combination with anastrozole versus anastrozole alone in 2 phase III
      trials, 1 by the Southwest Oncology Group and the other being conducted mainly in
      Scandinavia. Preclinical data have also led to randomized phase II trials of
      fulvestrant in combination with the epidermal growth factor receptor tyrosine
      kinase inhibitor, gefitinib, and the HER2/neu-targeted antibody trastuzumab.
      Additional phase II and III trials are currently evaluating fulvestrant plus
      tipifarnib, Theratope vaccine, or the dual kinase inhibitor, GW572016. Although
      fulvestrant is undergoing robust clinical development as a treatment for breast
      cancer, investigation of this agent in other types of solid tumors has only just
      begun.

PMID- 15865848
TI  - Clinical value of fulvestrant in breast cancer.

PMID- 15865849
TI  - The history and mechanism of action of fulvestrant.
AB  - Fulvestrant is a pure antiestrogen that emerged from a systematic medicinal
      chemistry strategy of modification of long-chain alkyl substitutes in the 7a
      position of estradiol. Fulvestrant has no uterotrophic effects on the immature or
      ovariectomized rat and blocks the agonistic effects of estradiol and tamoxifen in
      a dose-dependent manner. In in vivo and in vitro breast cancer models,
      fulvestrant has anticancer activity at least as good as tamoxifen and is superior
      to tamoxifen in some models. Fulvestrant requires intramuscular administration in
      a proprietary formulation of castor oil and alcohols. When fulvestrant binds to
      estrogen receptor monomers it inhibits receptor dimerization, activating function
      1 (AF1) and AF2 are rendered inactive, translocation of receptor to the nucleus
      is reduced, and degradation of the estrogen receptor is accelerated. This results
      in pure antiestrogenic effects. There is substantial preclinical evidence that
      the nonsteroidal hormone-dependent mechanisms of estrogen receptor activation and
      regulation via growth factor receptors and their signal transduction pathways are
      important in the development of breast cancer hormonal resistance. Methods of
      exploiting the interactions between these nonsteroidal hormone-dependent
      mechanisms of resistance and hormonal agents such as fulvestrant are an active
      area for drug development and clinical investigation.

PMID- 15865850
TI  - Effectiveness and tolerability of fulvestrant in postmenopausal women with
      hormone receptor-positive breast cancer.
AB  - Fulvestrant, an estrogen receptor antagonist that downregulates the estrogen
      receptor but has no known agonist effects, has been evaluated in 2 randomized
      trials involving postmenopausal women with hormone receptor-positive, progressive
      advanced-stage breast cancer after disease progression with antiestrogen therapy.
      These phase III studies, from which data were reported separately and in a
      planned combined analysis, showed that fulvestrant 250 mg per month
      intramuscularly was at least as effective as anastrozole 1 mg per day orally with
      respect to the primary endpoint of time to progression as well as secondary
      efficacy endpoints, which included objective response, clinical benefit, and
      survival. Both trials showed that patients treated with fulvestrant had a
      significantly longer duration of response, and a retrospective analysis found
      that pretreatment with fulvestrant did not preclude response to third-line
      hormonal therapy. More recently, fulvestrant was shown to be active as first-line
      hormonal therapy for advanced-stage breast cancer, with overall efficacy similar
      to that of tamoxifen in patients with hormone receptor-positive disease.
      Fulvestrant has been well tolerated in comparative trials published to date,
      translating into low study withdrawal rates and maintenance of quality of life.
      The incidence of adverse events was similar between the treatment arms in both
      trials of fulvestrant versus anastrozole, but it was notably lower for
      fulvestrant relative to tamoxifen in the first-line setting. In light of the
      results of comparative phase III trials, fulvestrant is effective and well
      tolerated in the treatment of postmenopausal women with hormone receptor-positive
      advanced-stage breast cancer.

PMID- 15865851
TI  - Atrial fibrillation: now one of the most common causes for hospitalization.

PMID- 15865852
TI  - Unique populations: different outcomes.

PMID- 15865853
TI  - Unique populations: different outcomes.

PMID- 15865854
TI  - Heart failure in women.
AB  - Increasingly high mortality from cardiovascular disease in women has sparked
      nationwide campaigns to raise awareness of this significant threat to women's
      health. Heart failure has the most lethal prognosis of the major cardiovascular
      diseases, yet women demonstrate an apparent survival advantage compared with men.
      Sex-linked disparities in heart failure risk factors and pathophysiology
      contribute to this divergent clinical outcome. Heart failure etiology and
      clinical manifestations unique to female sex exist. At age 40, the lifetime risk
      of developing heart failure is equal for men and women, whereas the lifetime risk
      of developing coronary heart disease is one in two for men and one in three for
      women. Understanding sex-inherent characteristics related to heart failure may
      help determine whether the optimal therapy for this prevalent syndrome should be
      modified according to sex. Until prospective trial data prove otherwise, heart
      failure treatment guidelines should be uniformly applied to both women and men.

PMID- 15865855
TI  - Cardiovascular disease in women: sex differences in presentation, risk factors,
      and evaluation.
AB  - Cardiovascular disease (CVD) is the leading cause of mortality in women.
      Pathophysiology, risk factors, clinical presentation, and outcomes of coronary
      artery disease (CAD) differ in women, and a better understanding of the sex
      differences in these factors will potentially lead to a slowing of this epidemic
      in women. Often forgotten, women have higher complication rates post
      revascularization and higher in-hospital mortality post myocardial infarction
      compared with men despite a smaller burden of disease in women. Though overall
      women share the same risk factors as men in the development of CAD, certain risk
      factors appear to be particularly ominous, such as the presence of diabetes
      mellitus, low values of high-density lipoprotein cholesterol, high triglycerides,
      and psychologic depression. Disease detection in advanced CAD is more accurate
      with stress echocardiography (ECG) and perfusion single-photon emission computed
      tomography imaging in women than with stress ECG. Subclincial atherosclerotic
      disease detection with carotid artery intima media thickness assessment provides
      an opportunity to target preventive measures in women. This article focuses on
      some of the sex-specific differences.

PMID- 15865856
TI  - Hypertrophy in the female heart.
AB  - Several clinical studies have suggested that sex influences the left ventricle's
      response to altered loading conditions and thus the development of cardiac
      hypertrophy. Likewise, several of the risk factors associated with the
      development of hypertrophy exhibit sexual dimorphism in their distribution in the
      general population. These sex-specific differences in risk factor distribution
      are likely important modifiers in disease progression and outcome. This review
      explores the available evidence of sex-specific differences in the evolution of
      left ventricular hypertrophy.

PMID- 15865857
TI  - Diastolic dysfunction and diastolic heart failure: mechanisms and epidemiology.
AB  - Studies have demonstrated that diastolic dysfunction is frequently present in
      asymptomatic community-based individuals, especially in the elderly with
      hypertension, coronary artery disease, and diabetes. The presence of diastolic
      dysfunction is a predictor for the development of heart failure (HF) and confers
      a higher risk of mortality. These findings have raised the question of whether
      treating preclinical diastolic dysfunction will be helpful in preventing or
      delaying the onset of clinical HF and mortality, as has been proven with
      treatment of asymptomatic left ventricular systolic dysfunction. In addition, in
      some individuals, diastolic dysfunction in the presence of a normal ejection
      fraction is associated with exercise intolerance as well as symptomatic clinical
      HF, referred to as diastolic HF. Patients with diastolic HF, who are more often
      elderly women, have a significant mortality and morbidity burden compared with
      age-matched controls. Studies that further our understanding of mechanisms
      underlying diastolic dysfunction and diastolic HF will provide potential new
      targets for development of effective therapies for these conditions.

PMID- 15865858
TI  - Advanced heart failure and transplantation in women.
AB  - Approximately half of the nearly 5 million people in the United States who have
      heart failure (HF) are women. The vast majority of women with advanced HF are
      elderly and many of them have HF with evidence of normal or preserved left
      ventricular systolic function. Although coronary disease is a common cause of HF
      for both men and women, a history of hypertension or diabetes places a woman at
      particular risk. Many fewer women than men have been enrolled in trials of
      therapies for patients with HF. Sex-specific results have been reported for some
      of these therapies, but not all trial data have been analyzed for sex-related
      differences. In spite of these differences in outcome, cardiac transplantation
      remains an important option for women with very advanced HF. Future research on
      therapies for HF will need to target women for enrollment, and all data analysis
      should include results that are stratified by sex.

PMID- 15865859
TI  - Nitric oxide donor therapy for patients with heart failure.

PMID- 15865860
TI  - Catheter ablation for atrial fibrillation in heart failure patients.

PMID- 15865861
TI  - Management of heart failure with pulmonary hypertension.
AB  - Heart failure (HF) and pulmonary hypertension (PH) coexist frequently and
      contribute to each other. Because PH often is an insidious disease, the
      cornerstone of management is the early identification and treatment of its
      underlying causes, such as left-sided heart disease, left to right shunts, and
      pulmonary disorders. A practical clinical classification has been proposed by the
      Third World Symposium on Pulmonary Arterial Hypertension for the purpose of
      diagnosis and treatment of PH. Thromboembolic pulmonary hypertension should
      always be considered. Recent studies using vasodilators such as prostacyclins and
      endothelin antagonists give new hope in the otherwise poor prognosis of
      idiopathic pulmonary arterial hypertension and its related conditions. Despite
      optimum medical management, transplantation (lung/heart-lung) remains the choice
      in severely symptomatic patients.

PMID- 15865862
TI  - Management of diuretic-refractory, volume-overloaded patients with acutely
      decompensated heart failure.
AB  - Fluid overload is a common presentation for decompensated heart failure, yet
      management strategies are poorly defined because of relatively few randomized
      clinical trials that delineate an optimal strategy. Patients refractory to
      diuretic therapy may be considered for treatment with inotropes or vasodilators,
      and others may be considered for venovenous ultrafiltration. The rationale for
      use of each therapy is reviewed.

PMID- 15865863
TI  - The link between obstructive sleep apnea and heart failure: underappreciated
      opportunity for treatment.
AB  - Obstructive sleep apnea (OSA) is a newly recognized risk factor for the
      development of systemic hypertension, ischemic heart disease and congestive heart
      failure. Mechanisms responsible for these links include OSA-related hypoxemia and
      arousal from sleep-induced increased sympathetic activity, large negative
      intrathoracic pressure-induced increased left ventricular transmural pressure
      gradient, and impaired vagal activity plus oxygen radial formation. Secondary
      phenomena include increased platelet aggregability, insulin resistance, and
      endothelial dysfunction with reduced endogenous nitric oxide production. Safe
      nonpharmacologic, nonsurgical therapy, namely continuous positive airway
      pressure, can attenuate OSA, and improve cardiac function and quality of life.
      Searching for signs or symptoms of OSA from the patient (or bed partner), namely
      loud habitual snoring, apneas, nocturnal choking, orthopnea, paroxysmal nocturnal
      dyspnea, excessive daytime sleepiness, or cardiovascular disease, which is
      difficult to control, may reward the curious physician with another treatment
      avenue.

PMID- 15865864
TI  - Exercise training in heart failure.
AB  - The reduction of exercise capacity with early occurrence of fatigue and dyspnea
      is a hallmark of heart failure syndrome. There are objective similarities between
      heart failure and muscular deconditioning. Deficiencies in peripheral blood flow
      and skeletal muscle function, morphology, metabolism, and function are present.
      The protective effects of physical activity have been elucidated in many recent
      studies: training improves ventilatory control, skeletal muscle metabolism,
      autonomic nervous system, central and peripheral circulation, and heart function.
      These provide the physiologic basis to explain the benefits in terms of survival
      and freedom from hospitalization demonstrated by physical training also in heart
      failure.

PMID- 15865865
TI  - Indications for implantable cardiac defibrillators in patients with congestive
      heart failure: implications of the sudden cardiac death in heart failure trial.
AB  - Sudden cardiac death (SCD) is a significant cause of mortality in patients
      suffering from heart failure and left ventricular dysfunction. Implantable
      cardioverter defibrillators have been shown to effectively reduce the incidence
      of SCD in this population. Recent clinical trials have redefined the indications
      and patient profiles for their use: from secondary prevention to primary
      prevention of SCD. In this article, we review the clinical trials contributing to
      the current practice guidelines, which include device therapy.

PMID- 15865867
TI  - Treatment of myelodysplastic syndromes with valproic acid alone or in combination
      with all-trans retinoic acid.

PMID- 15865866
TI  - ADAMTS13, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome.

PMID- 15865868
TI  - The clinical implications of the World Health Organization's classification of
      myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of neoplastic clonal
      stem cell diseases characterized by dysplastic morphological features with a
      varying percentage of leukemic blasts and clinical bone marrow failure. The
      French-American-British (FAB) system served as the gold standard of MDS
      classification for more than two decades. The World Health Organization (WHO)
      classification, built on the backbone of the FAB classification, is an attempt to
      further improve the prognostic value of MDS classification as well as to
      establish its clinical utility as a tool to select different treatments. In this
      article we highlight the major differences between the FAB classification and the
      WHO MDS classification. We discuss in more details the experience of using the
      new WHO classification since its publications and review the studies that tried
      to either validate the prognostic value of the new classification or apply it to
      predict clinical responses to various treatments.

PMID- 15865869
TI  - Lenalidomide (Revlimid, CC-5013) in myelodysplastic syndromes: is it any good?
AB  - The myelodysplastic syndromes (MDS) can be divided into "early" and "advanced"
      disease by evaluation of prognostic variables such as the number of cytopenias,
      karyotype, and percentage of myeloblasts. Patients with an isolated interstitial
      deletion of chromosome 5q31 represent a distinct subset who may derive particular
      benefit from immunomodulatory drugs. Goals of therapy for early MDS focus on
      hematologic improvement and maximizing quality of life. Thalidomide, the
      prototype of the immunomodulatory drugs, yields major erythroid responses in some
      patients with early MDS, but dose-limiting neurologic toxicities limit its
      potential clinical benefit. Lenalidomide, a more potent and non-neurotoxic
      derivative, has shown promising results in early MDS, yielding hematologic
      improvement in almost half of patients, and transfusion independence with
      cytogenetic remissions in approximately two thirds of patients harboring the
      chromosome 5q31 deletion.

PMID- 15865870
TI  - Farnesyltransferase inhibitors in myelodysplastic syndrome.
AB  - The farnesyltransferase inhibitors (FTIs) are in active clinical development in a
      variety of human malignancies. The most promising activity to date has been
      demonstrated in patients with hematological malignancies, in particular acute
      myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In patients with MDS,
      two non-peptidomimetic agents, tipifarnib (Zarnestra, Johnson & Johnson, New
      Brunswick, NJ) and lonafarnib (Sarasar, Schering-Plough, Kenilworth, NJ) have
      been the most extensively studied. In both phase I and phase II trials,
      tipifarnib has demonstrated significant efficacy with overall response rates of
      30%, with complete remissions in about 15%. Dose-limiting side effects have been
      primarily myelosuppression, although fatigue, neurotoxicity, and occasional renal
      dysfunction have required dose reductions. Lonafarnib in patients with MDS has
      also resulted in clinical responses in approximately 30%, including significant
      improvements in platelet counts. Lonafarnib has been associated with primarily
      diarrhea and other gastrointestinal toxicity, anorexia, and nausea, which has
      limited its efficacy. Clinical response correlation with documentation of
      inhibition of farnesyltransferase and/or evidence of decreased farnesylation of
      downstream protein targets has not been demonstrated with either agent. In
      addition, the presence of an activating Ras mutation has not predicted response
      to therapy with FTIs in MDS and AML. Despite this, significant clinical efficacy
      of the FTIs in MDS, on par with that of currently available chemotherapeutic
      agents, has been observed, leading to further development of this new class of
      drugs in MDS and AML.

PMID- 15865871
TI  - New agents in myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic
      disorders characterized by ineffective hematopoiesis resulting in peripheral
      cytopenia and by increased progression to acute myeloid leukemia (AML).
      Therapeutic interventions for MDS other than allogeneic stem cell transplantation
      have been palliative. Novel and targeted therapeutic agents such as the
      inhibition of farnesyl transferases and receptor tyrosine kinases, more potent
      thalidomide analogs, arsenic trioxide, immunomodulating agents, hypomethylating
      agents, and histone deacetylase inhibitors have shown encouraging results and may
      offer durable benefit to patients with MDS. Further development of rational
      therapies and improvements in the outcome of patients with MDS are likely to
      emerge from an increased understanding of the pathophysiology of these diseases.

PMID- 15865872
TI  - Bone marrow transplant in myelodysplastic syndromes: new technologies, same
      questions.
AB  - Myelodysplastic syndrome (MDS) comprises a heterogeneous group of hematologic
      disorders characterized by a clonal abnormality of hematopoietic stem cells that
      results in a varying degree of cytopenias and risk of transformation into acute
      leukemia. Only allogeneic transplant has been shown to cure this disease.
      However, high nonrelapse mortality rates limit the applicability of conventional
      allografts and, even in young patients, long-term disease control ranging from
      only 30% to 50% has been reported. Novel transplant regimens, availability of
      alternative donors, and busulfan targeting promise to increase transplant
      applicability and reduce nonrelapse mortality rates. However, high relapse rates
      in patients with high-risk disease limit the success of this procedure to the
      point that a definite advantage of allografting over standard therapy remains
      controversial. New agents being developed for MDS may have a potential impact on
      transplant outcomes. Therefore, design and implementation of clinical trials of
      transplant for MDS should be encouraged to improve the natural history of this
      disease.

PMID- 15865873
TI  - Hydroxyurea vindicated: lack of drug leukemogenicity in polycythemia vera.

PMID- 15865874
TI  - The rise and fall of red cell mass measurement in polycythemia vera.
AB  - The total blood volume (BV) consists of the part occupied by red blood cells
      (RBC), which is referred to as red cell mass (RCM), and that occupied by plasma
      (ie, plasma volume). Quantitative laboratory measurements that are pertinent to
      RBC, including RBC count, hematocrit (Hct), and hemoglobin (Hgb) are expressed in
      reference to a given volume of whole blood and are therefore influenced by plasma
      volume. Consequently, a "direct" RCM measurement has been promoted as a more
      accurate indicator of the body's red cell content. In accordance with this view,
      an international group of investigators, then identified as the Polycythemia Vera
      Study Group (PVSG), recommended that RCM be measured and only if elevated should
      a patient be considered for participation in a series of clinical trials in PV
      that were conducted more than 30 years ago. By default, the 'study eligibility'
      criteria used in these studies became 'diagnostic' criteria without any
      systematic evaluation for diagnostic accuracy. Furthermore, over the years, it
      has become evident that RCM measurement is a cumbersome and costly test that is
      also suboptimal in its diagnostic accuracy. As a result, the specific procedure
      has been abandoned by the majority of hematologists in certain countries and
      instead physicians are increasingly using bone marrow histology, serum
      erythropoietin level, and other disease-characteristic biologic markers as
      diagnostic tools.

PMID- 15865875
TI  - Diagnosis of polycythemia vera based on bone marrow pathology.
AB  - The diagnostic criteria of the Polycythemia Vera Study Group (PVSG) do not
      include bone marrow (BM) examinations. The aim of this review is to elucidate
      whether distinctive patterns of histopathology exist which discriminate reactive
      (secondary polycythemia) from autonomous (polycythemia vera) erythrocytosis. When
      accompanied by an elevated platelet count, the initial stages of PV may
      clinically mimic essential thrombocythemia because they are not recognized by the
      conventional diagnostic criteria. Our data are derived from previous studies and
      evaluations of 362 patients with a borderline to marked increase in hemoglobin.
      PV revealed a trilineage myeloproliferation (panmyelosis) with a pleomorphous
      appearance (ie, differences in size) of loosely clustered megakaryocytes that
      failed to show gross cytological anomalies. Distinction from SP was accomplished
      by regarding megakaryopoiesis and the stromal changes (perivascular
      plasmacytosis, eosinophils, cell debris, and iron deposits). Discriminant
      analysis of standardized BM features, based on semiquantitative evaluation,
      yielded a sensitivity of 96% concerning the clear-cut separation of PV from SP.

PMID- 15865876
TI  - Karyotype and molecular cytogenetic studies in polycythemia vera.
AB  - A minority of patients with newly diagnosed polycythemia vera (PV) have an
      abnormal karyotype in their myeloid cells but no invariant chromosomal aberration
      has been found. The most frequent visible alteration is a 20q deletion, also
      characterized in other myeloproliferative diseases (MPD) and myeloid
      malignancies; among other chromosomal changes, trisomy 9 appears more common in
      PV than in other MPDs. When a myelofibrosis complicates the course of the
      disease, cytogenetic anomalies become quite common with a striking frequency of
      partial duplication 1q; an evolution towards myelodysplasia or acute leukemia is
      almost always associated with nonspecific chromosomal aberrations. Modern
      cytogenetic methods have disclosed cryptic anomalies and pointed out the high
      frequency of 9p alterations affecting a restricted region, thus stimulating an
      active search for candidate genes or specific mutations.

PMID- 15865877
TI  - Polycythemia vera: plethora, from prehistory to present.
AB  - The term polycythemia (literally, "many blood cell disease") and its obsolete
      synonym, erythremia, postdate Robert Hooke's 17th century discovery of cells, but
      the concept of a clinically problematic excess of blood was formulated in
      antiquity. Observation of plethoric patients by clinicians of the Hippocratic
      school informed the classical humoral framework that dominated theoretical
      constructs of human disease for more than a thousand years. In the golden era of
      disease description at the end of the 19th century, the idiopathic entity
      polycythemia rubra vera (PRV) was first described and distinguished from
      secondary and relative polycythemia (red cell excess not caused by a primary bone
      marrow disorder, and artifactual red cell excess caused by plasma volume
      contraction, respectively). This review traces some of the principal events in
      the history of polycythemia vera (PV) as a discrete clinical entity.

PMID- 15865878
TI  - Treatment of polycythemia vera with recombinant interferon alpha (rIFNalpha) or
      imatinib mesylate.
AB  - Polycythemia vera (PV) is a myeloproliferative disease which if untreated leads
      to thrombohemorrhagic complications and eventually to progressive myelofibrosis
      of the marrow, anemia, and splenomegaly. Two new drugs are now available,
      interferon and imatinib mesylate, which may alter the course of this disease.
      Used as single agents, each produces lasting remissions in about 75% of the
      cases.

PMID- 15865880
TI  - Obesity: outwitting the wisdom of the body?

PMID- 15865879
TI  - Recent advances in the molecular biology of congenital polycythemias and
      polycythemia vera.
AB  - This review will focus on the molecular basis of certain polycythemic disorders.
      Primary polycythemias are characterized by acquired somatic or inherited germ
      line mutations expressed within hematopoietic progenitors that cause increased
      accumulation of red blood cells. Polycythemia vera (PV), an acquired condition,
      is the most common primary polycythemia; although some progress has been made in
      the understanding of PV, its molecular basis remains unknown. In contrast, recent
      advances in delineating the molecular defects of some inherited polycythemias
      have greatly furthered our knowledge of the regulation of erythropoiesis and
      hypoxia sensing; however, more work needs to be done.

PMID- 15865881
TI  - Concomitant chemoradiotherapy followed by adjuvant temozolomide improves survival
      in glioblastoma multiforme.

PMID- 15865882
TI  - Update on brain tumor imaging.
AB  - Brain tumor imaging has evolved from a strictly morphology-based discipline to
      one that encompasses function, physiology, and anatomy, enabled by advances in
      imaging and computer technology. This review outlines the current imaging
      standard for patients with brain tumors and summarizes the latest advances in
      physiology-based imaging methods that complement traditional brain tumor imaging
      protocol. Emphasis is placed on the strengths and limitations of the current
      imaging standards and on an overview of several advanced imaging methods,
      including diffusion-weighted magnetic resonance imaging, perfusion magnetic
      resonance imaging, and proton magnetic resonance spectroscopic imaging. Basic
      physical principles behind each imaging method are briefly presented, along with
      a more in-depth discussion of the clinical applications and potential pitfalls of
      each technique.

PMID- 15865883
TI  - Update on the medical management of pituitary adenomas.
AB  - The medical treatment of pituitary adenomas has changed significantly over the
      past decade. Pharmacologic therapy for prolactinomas in the form of dopamine
      agonists has been available since the 1970s, and somatostatin analogues for
      treatment of growth hormone (GH)-secreting adenomas were introduced in the 1980s.
      However, the recent introduction of long-acting forms of these agents has
      markedly improved efficacy. Furthermore, long-acting somatostatin analogues also
      have utility in treating thyrotropin adenomas and a subset of adrenocorticotroph
      tumors. Limited clinical studies with long-acting dopamine agonists suggest that
      a subset of patients with GH, adrenocorticotroph, and gonadotropin/nonsecreting
      adenomas may also benefit from therapy with these agents. The introduction of a
      GH receptor antagonist in the 1990s has added to the pharmacologic armamentarium
      for treatment of acromegaly. In parallel with improved medical therapy, hormonal
      assays for assessing tumor activity have improved in sensitivity, necessitating
      new standards for treatment optimization. This article highlights some of these
      evolving new ideas and approaches to the pharmacologic management of pituitary
      adenomas.

PMID- 15865885
TI  - Optimal role of temozolomide in the treatment of malignant gliomas.
AB  - Temozolomide (TMZ) is an alkylating agent that was approved for anaplastic
      astrocytoma and glioblastoma. Its role in the treatment of recurrent disease has
      been confirmed, and more importantly, alternative treatment schedules and
      combination regimens have been developed. A recent phase III trial has
      demonstrated a survival advantage for concomitant TMZ administration with
      radiotherapy in patients with newly diagnosed glioblastoma. Molecular studies
      suggest a strong predictive role of the DNA repair enzyme O6-methyl-guanine-DNA
      methyl-transferase (MGMT) and outcome of TMZ-based chemotherapy. This review
      summarizes the current knowledge, highlights approved and nonapproved
      indications, and describes molecular studies that may allow us to identify the
      patients most likely to benefit from this treatment.

PMID- 15865884
TI  - Targeted molecular therapy of malignant gliomas.
AB  - Malignant gliomas are the most common form of primary brain tumors in adults.
      Despite advances in diagnosis and standard therapies such as surgery, radiation,
      and chemotherapy, the prognosis remains poor. Recent scientific advances have
      enhanced our understanding of the biology of gliomas and the role of tyrosine
      kinase receptors and signal transduction pathways in tumor initiation and
      maintenance, such as the epidermal growth factor receptors, platelet-derived
      growth factor receptors, vascular endothelial growth factor receptors, and the
      Ras/Raf/mitogen-activated protein (MAP)-kinase and phosphatidylinositol-3 kinase
      (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathways. Novel targeted drugs
      such as small molecular inhibitors of these receptors and signaling pathways are
      showing some activity in initial studies. As we learn more about these drugs and
      how to optimize their use as single agents and in combination with radiation,
      chemotherapy, and other targeted molecular agents, they will likely play an
      increasing role in the management of this devastating disease. This review
      summarizes the current results with targeted molecular agents in malignant
      gliomas and strategies under evaluation to increase their effectiveness.

PMID- 15865886
TI  - Optimal seizure management in brain tumor patients.
AB  - The mechanism of epilepsy in brain tumor patients is probably multifactorial, and
      its incidence depends on tumor type and location. Refractory epilepsy is common
      in patients with a structural brain lesion, and a role for multidrug resistance
      proteins has been suggested. Until now, the medical treatment of epilepsy in
      brain tumor patients has only been studied retrospectively. Therefore, the
      optimal seizure management by antiepileptic drugs (AEDs) in this patient category
      is essentially unsure. Choices depend on the outcome of retrospective studies, a
      few nonrandomized series, extrapolation from other studies in symptomatic
      epilepsy, and anticipated interactions, most notably between AEDs and anticancer
      agents. The newly developed AEDs levetiracetam and gabapentin are recommended
      because of good results in preliminary studies and because they do not show
      interactions with anticancer agents. The use of prophylactic AEDs in brain tumor
      patients is disputable and generally not advised.

PMID- 15865887
TI  - Recent advances in the neuroimaging of multiple sclerosis.
AB  - Neuroimaging studies continue to provide important insights into the central
      nervous system disease pathology of multiple sclerosis (MS). Although
      conventional magnetic resonance imaging remains the mainstay of diagnosis and
      laboratory assessment of therapeutic response in MS, quantitative techniques
      continue to extend our understanding of both macroscopic and microscopic disease
      processes. Over the past year, many published studies have investigated measures
      of brain atrophy, gray matter involvement, vascular properties, and myelin and
      neuronal loss and have examined their relationship to clinical disease
      expression, genotype, and therapy. An important trend continuing over the past
      year is the development of targeted agents to improve the pathologic specificity
      of imaging measures. Specific disease measures such as endothelial activation,
      microglial activation, and cell trafficking are accessible to neuroimaging and
      offer significant promise for improved characterization of central nervous system
      involvement in MS.

PMID- 15865888
TI  - Stem cell therapy for central nervous system demyelinating disease.
AB  - Recent advances in cell-based therapies for demyelinating central nervous system
      diseases have demonstrated the ability to restore damaged neuronal architecture
      and function. Demyelinated axons in patients with multiple sclerosis can
      spontaneously remyelinate over time; however, the rate and extent at which
      remyelination occurs is inadequate for complete recovery. Previous attempts aimed
      at regenerating myelin-forming cells have been successful but limited by the
      multifocal nature of the lesions and the inability to produce large numbers of
      myelin-producing cells in culture. Stem cell-based therapy can overcome these
      limitations to some extent and may prove useful in the future treatment of
      demyelinating diseases.

PMID- 15865889
TI  - Nitric oxide and multiple sclerosis.
AB  - Nitric oxide (NO) is a free radical signaling molecule with remarkably complex
      biochemistry. Its involvement in multiple sclerosis (MS) had been postulated soon
      after the discovery of the critical role NO plays in inflammation. However, the
      extent of NO's contribution to MS is not yet understood, party due to the often
      opposing roles that NO can play in cellular processes. This review briefly covers
      new developments in the area of NO that may be relevant to MS. It also describes
      recent progress in understanding the role of NO in MS, new potential targets of
      the action of NO in the cell, and prospects for NO-based therapies.

PMID- 15865890
TI  - Role of microglia in multiple sclerosis.
AB  - Microglia are the resident macrophages of the nervous system. They serve to
      protect and preserve neuronal cells from pathogens and facilitate recovery from
      metabolic insults. In addition, they appear to play a role in the neuropathology
      of noninfectious inflammatory disorders of the central nervous system, especially
      those that are autoimmune. Presentation of neural autoantigens to autoreactive T
      cells by microglia and the attendant secretion of proinflammatory cytokines are
      thought to facilitate the inflammatory process in diseases such as multiple
      sclerosis. They also serve as scavengers of damaged myelin following death of
      oligodendrocytes and the destruction of myelin and may, therefore, promote
      recovery of myelin damaged by the inflammatory insult. This review examines the
      current controversies on the pathology of multiple sclerosis and the role played
      by microglia in the development of central nervous system demyelination.

PMID- 15865891
TI  - Combination therapy in multiple sclerosis.
AB  - Over the past decade, multiple sclerosis (MS) has become a treatable neurologic
      illness. However, given the rather modest benefit of the currently available
      disease-modifying agents, as well as the challenges associated with performing
      placebo-controlled, equivalence, and superiority trials, the logic of combining
      therapies in MS has considerable appeal. Selecting agents for combination
      requires careful consideration, as the immunomodulating activity of one drug
      could potentially interfere with the therapeutic effect of another, and certain
      combinations may be associated with unforeseen adverse effects. Rigorously
      controlled studies are needed to determine the safest and most effective use of
      new and existing MS therapies.

PMID- 15865892
TI  - An unseen epidemic.

PMID- 15865898
TI  - Preventing recurrent ischemic stroke: a 3-step plan.

PMID- 15865899
TI  - "My airway is closing".

PMID- 15865900
TI  - How should we care for atopic dermatitis?

PMID- 15865901
TI  - Hormone replacement therapy: the right choice for your patient?

PMID- 15865902
TI  - The growing threat of avian influenza.

PMID- 15865903
TI  - Type 2 diabetes: the role of insulin.

PMID- 15865904
TI  - ARBs vs ACE inhibitors for preventing diabetic nephropathy.

PMID- 15865905
TI  - Making the most of the time we have.

PMID- 15865906
TI  - Clinical inquiries. What is the appropriate diagnostic evaluation of fibroids?

PMID- 15865907
TI  - Clinical inquiries. Should a nylon brush be used for Pap smears from pregnant
      women?

PMID- 15865908
TI  - Clinical inquiries. What is the best approach to the evaluation of hirsutism?

PMID- 15865909
TI  - Clinical inquiries. Is DEET safe for children?

PMID- 15865910
TI  - Clinical inquiries. What is angular cheilitis and how is it treated?

PMID- 15865911
TI  - Clinical inquiries. Do beta-blockers worsen respiratory status for patients with
      COPD?

PMID- 15865912
TI  - The effect of emotional context on cognitive inhibition and attentional
      processing in dissociative identity disorder.
AB  - In light of previous research, the current study tested the hypothesis that
      dissociative identity disorder (DID) would be characterised by effective
      cognitive inhibitory functioning when tested in a neutral context, but weakened
      inhibition when tested in an emotionally negative context. Using a negative
      priming task (i.e. the flanker task) to assess inhibitory ability 11 DID, 11
      depressed, and 11 general population participants were tested in the two
      differing experimental contexts. The contexts were manipulated by instructions
      and word stimuli, and following the completion of this task participants
      completed the Dissociative Experiences Scale and the Schizotypal Personality
      Scale. DID participants displayed a greater degree of self-reported anxiety in
      the negative context and as expected displayed a reduction in inhibition in this
      context but not in the neutral context. The degree of negative priming for the
      depressed and general population samples remained stable across contexts as did
      their anxiety levels. The DID sample displayed slower response times to negative
      compared to neutral words but this attentional bias was not evident for the two
      comparison groups. The relationship between increased arousal, inhibitory
      functioning, dissociation and information processing in DID is discussed.

PMID- 15865913
TI  - Peritraumatic dissociation and experiential avoidance as predictors of
      posttraumatic stress symptomatology.
AB  - This study examined whether peritraumatic dissociation serves as a proxy risk
      factor for experiential avoidance in its relationship with posttraumatic stress
      disorder (PTSD) symptomatology. One hundred eighty-five trauma survivors
      completed measures that assessed for peritraumatic dissociation, experiential
      avoidance, and PTSD symptom severity. The results indicated that peritraumatic
      dissociation and experiential avoidance were significantly related to PTSD
      symptomatology at baseline. However, after initial levels of PTSD symptomatology
      were taken into account, only experiential avoidance was related to PTSD symptoms
      both 4- and 8-weeks later. These results indicate that peritraumatic dissociation
      is not a proxy risk factor for experiential avoidance and contributes to the
      growing body of literature indicating that experiential avoidance is an important
      factor related to the psychological symptoms experienced by trauma survivors.

PMID- 15865914
TI  - An abbreviated PTSD checklist for use as a screening instrument in primary care.
AB  - Although the importance of recognizing posttraumatic stress disorder (PTSD) in
      primary care has been well-established, routine screening for PTSD remains
      unfeasible for many primary care clinics because of the length of the available
      screening instruments. Thus, the purpose of this work was to develop and validate
      a brief screening tool for PTSD. In Study 1, four short forms of the PTSD
      Checklist-civilian version were identified that captured a majority of the
      variance in the measure. In Study 2, the performance of these short forms was
      evaluated in a separate sample of primary care patients. We found that both two
      item and six-item versions have adequate psychometric properties for screening
      purposes and suggest that the selection of one version over the other depends on
      the specific needs of each primary care clinic.

PMID- 15865915
TI  - Does sound stimulation have additive effects on cognitive-behavioral treatment of
      chronic tinnitus?
AB  - Psychological and physiological habituation are major goals in the treatment of
      patients suffering from chronic tinnitus. This study evaluates whether sound
      stimulation provided by use of low level white noise generators (NG) enhances the
      effects of cognitive-behavioral treatment (CBT). 124 outpatients with tinnitus of
      >6 months received manualized group treatment and were randomly assigned to the
      NG/no NG conditions. Those with moderate tinnitus-related distress obtained four
      sessions focusing on education, while severely distressed subjects were treated
      according to a full 10-session CBT program. Outcome was assessed at post
      treatment and at 6- and 18-month follow-up. No additive effects due to the NGs
      could be demonstrated. All groups improved significantly on measures of tinnitus
      related distress, dysfunctional cognitions, general psychopathology, depression,
      hypochondriasis and psychosocial functioning. Beneficial effects of the NGs were
      only observed for patients with concurrent tinnitus and hyperacusis. As
      systematic physical stimulation of the auditory system does not further improve
      the effects of CBT, the importance and strength of psychological interventions
      are emphasized. The clinical relevance of recently developed "retraining"
      approaches accentuating physical stimulation should be reconsidered.

PMID- 15865916
TI  - Unwanted memories of assault: what intrusion characteristics are associated with
      PTSD?
AB  - Intrusive memories are common in the immediate aftermath of traumatic events, but
      neither their presence or frequency are good predictors of the persistence of
      posttraumatic stress disorder (PTSD). Two studies of assault survivors, a cross
      sectional study (N=81) and a 6-month prospective longitudinal study (N=73),
      explored whether characteristics of the intrusive memories improve the
      prediction. Intrusion characteristics were assessed with an Intrusion Interview
      and an Intrusion Provocation Task. The distress caused by the intrusions, their
      "here and now" quality, and their lack of a context predicted PTSD severity. The
      presence of intrusive memories only explained 9% of the variance of PTSD severity
      at 6 months after assault. Among survivors with intrusions, intrusion frequency
      only explained 8% of the variance of PTSD symptom severity at 6 months. Nowness,
      distress and lack of context explained an additional 43% of the variance. These
      intrusion characteristics also predicted PTSD severity at 6 months over and above
      what could be predicted from PTSD diagnostic status at initial assessment.
      Further predictors of PTSD severity were rumination about the intrusive memories,
      and the ease and persistence with which intrusive memories could be triggered by
      photographs depicting assaults. The results have implications for the early
      identification of trauma survivors at risk of chronic PTSD.

PMID- 15865917
TI  - Body checking and avoidance and the core features of eating disorders among obese
      men and women seeking bariatric surgery.
AB  - This study examined two aspects of body checking and avoidance, and their
      relations to the core psychopathology of eating disorders (EDs), in severely
      obese men and women seeking bariatric surgery. A consecutive series of 260 (44
      male and 216 female) gastric bypass candidates were administered measures to
      assess body checking and avoidance, binge eating, restraint, and overevaluation
      of weight and shape. The majority of patients reported regularly pinching areas
      of their body to check for fatness and avoided wearing clothing that made them
      particularly aware of their body. Significant associations were observed between
      checking and restraint, and between avoidance and binge eating. Both checking and
      avoidance behaviors were significantly associated with overevaluation of weight
      and shape. The positive associations between each of the two behaviors (body
      checking and avoidance) with overevaluation of weight/shape remained significant
      even after controlling for the effects of avoidance on body checking and vice
      versa. Stepwise multiple regression analyses revealed that binge eating, body
      checking, and avoidance behaviors made significant unique contributions and
      jointly accounted for 22-25% of the variance in overevaluation of weight and
      shape, respectively. This study documents the presence of eating disorder
      psychopathology among severely obese patients seeking bariatric surgery. The
      findings support the view that body checking and avoidance behaviors are
      manifestations of overevaluation of weight and shape and disordered eating.

PMID- 15865918
TI  - Social phobics do not misinterpret facial expression of emotion.
AB  - Attentional biases in the processing of threatening facial expressions in social
      anxiety are well documented. It is generally assumed that these attentional
      biases originate in an evaluative bias: socially threatening information would be
      evaluated more negatively by socially anxious individuals. However, three studies
      have failed to evidence a negative evaluative bias in the processing of emotional
      facial expression (EFE) in socially anxious individuals. These studies however
      suffer from several methodological limitations that the present study has
      attempted to overcome. Twenty-one out-patients diagnosed with generalized social
      phobia have been compared to 20 out-patients diagnosed with another anxiety
      disorder and with 39 normal controls matched for gender, age and level of
      education. They had to decode on seven emotion intensity scales a set of 40 EFE
      whose intensity and emotional nature were manipulated. Although sufficient
      statistical power was ensured, no differences among groups could be found in
      terms of decoding accuracy, attributed emotion intensity, or reported difficulty
      of the task. Based on these findings as well as on other evidences, we propose
      that, if they exist, evaluative biases in social anxiety should be implicit and
      automatic and that they might be determined by the relevance of the stimulus to
      the person's concern rather than by the stimulus valence. The implications of
      these findings for the interpersonal processes involved in social phobia are
      discussed.

PMID- 15865919
TI  - A prospective study of pressures from parents, peers, and the media on extreme
      weight change behaviors among adolescent boys and girls.
AB  - The current study was designed to evaluate the role of sociocultural influences
      over a 16 month period on strategies to lose weight, extreme weight loss
      strategies, and strategies to increase muscles among adolescent boys (n=344) and
      girls (n=246). All participants completed measures of body dissatisfaction, body
      image importance, strategies to lose weight, extreme weight loss strategies, and
      strategies to increase muscles. Measures of perceived pressure to lose weight or
      increase muscles from mother, father, best male friend, best female friend and
      the media were also evaluated. Data were gathered on three occasions, 8 months
      apart. The results demonstrated that boys showed a decrease in strategies to lose
      weight and increase muscles over time, whereas girls showed an increase. Both
      boys and girls showed an increase in extreme weight loss strategies with girls
      demonstrating a greater increase than boys. The sociocultural influences
      generally were perceived by girls to relate to messages to lose weight, whereas
      for boys they were perceived to relate to increasing muscles. Messages from
      parents, particularly fathers, were strong predictors of both strategies to lose
      weight and increase muscles among boys, with the media and best male friend
      playing a limited role. For girls, the strongest influences were mothers and best
      female friends, with few influences from fathers or the media. The results of
      this study are discussed in terms of the importance of the various sociocultural
      influences in shaping body change strategies among young adolescent boys and
      girls, and the implications of these findings for intervention programs for
      adolescents.

PMID- 15865920
TI  - Brief cognitive-behavioral phone-based intervention targeting anxiety about the
      threat of attack: a pilot study.
AB  - A brief, cognitive-behavioral, phone-based intervention was employed with an
      Israeli sample experiencing anticipatory anxiety about potential war-related
      attacks. In this quasi-experimental controlled pilot study, the cognitive
      behavioral therapy intervention (diaphragmatic breathing and a modified cognitive
      restructuring technique) was compared with the standard hotline care administered
      when worried citizens called a mental health emergency hotline in Israel.
      Individuals (n=32) were administered anxiety and worry measures pre-intervention,
      post-intervention, and three days post-intervention. The results indicated that
      anxiety levels decreased for the experimental and control group immediately post
      intervention; however, three days later, the levels of anxiety in the CBT group
      continued to decline, while anxiety levels in the control group reached pre
      intervention levels on two of the three outcome measures. These results suggest
      that CBT can be effectively delivered by paraprofessionals over the phone, which
      is cost-effective and efficient. Limitations are considered, and implications for
      treating individuals coping with the threat of terrorism are discussed.

PMID- 15865921
TI  - Controlled and automatic uses of memory in depressed patients: effect of
      retention interval lengths.
AB  - The present study examines controlled and automatic uses of memory in clinically
      depressed patients by applying the Process Dissociation Procedure developed by
      Jacoby (1991) to a stem completion memory task with short and long retention
      intervals. The results show that the contribution of controlled processes is
      lower in depressed patients than in controls, especially for the longest
      retention interval, whereas the contribution of automatic processes is equivalent
      in both groups and unaffected by the length of the retention interval. These
      findings are discussed in a cognitive control framework.

PMID- 15865922
TI  - p53 in apoptosis control: an introduction.

PMID- 15865923
TI  - p73-induced apoptosis: a question of compartments and cooperation.
AB  - The transcriptionally active forms of p73 are capable of inducing apoptosis, and
      the isoforms termed TAp73 are important players when E2F and its oncogenic
      activators induce programmed cell death. However, the conditions under that TAp73
      can kill a cell remain to be clarified. Recently, it has been found that p73
      proteins are not merely floating in the nucleoplasm but rather can associate with
      specific compartments in the cell. Examples of intranuclear compartments
      associated with p73 proteins include the PML oncogenic domains and the nuclear
      matrix. In addition, p73 is found in the cytoplasm. It remains to be seen whether
      p73 might also associate with mitochondria, in analogy with p53. The
      relocalization of p73 is expected to be mediated by specific binding partners,
      mostly other proteins. Here, we discuss the possibility that the
      compartmentalization of p73, and the cooperation with the corresponding binding
      partners, might decide about its apoptosis-inducing activity.

PMID- 15865924
TI  - Guilt by association? p53 and the development of aneuploidy in cancer.
AB  - Aneuploidy is one of the most frequent genetic alterations in solid tumors. It is
      commonly caused by cell division errors that are induced by oncogene activation
      or loss of tumor suppressor functions. In addition, certain viral oncoproteins
      have been implicated in the induction of chromosome copy number changes.
      Aneuploidy and inactivation of p53 frequently coincide in human cancers but there
      is increasing evidence that loss of p53 by itself is not a primary cause of
      aneuploidy. Nonetheless, p53 inactivation synergizes with additional oncogenic
      events to promote aneuploidy and may facilitate chromosomal imbalances through
      indirect mechanisms. This review summarizes the current knowledge about the
      association between aneuploidy and p53, and discusses two of the most
      controversial mechanisms that have been implicated in genomic instability
      associated with loss of p53: subversion of ploidy control and aberrant centrosome
      duplication.

PMID- 15865925
TI  - p53-A pro-apoptotic signal transducer involved in AIDS.
AB  - P53 is a well-characterized tumor suppressor protein, which can induce apoptosis,
      either by inducing transcription of pro-apoptotic genes or by direct effects on
      mitochondrial membranes. Roughly 50% of human cancers are affected by the genetic
      or epigenetic inactivation of p53. Recently, p53 has been incriminated to play a
      cardinal role in the destruction of the immune system by human immunodeficiency
      virus (HIV-1) infection. This suspicion is based on several lines of evidence:
      (i) p53 exhibits activating phosphorylations in a subset of peripheral blood
      mononuclear cells and lymph node cells from HIV-1 carriers; (ii) some p53 target
      genes (e.g., PUMA, a pro-apoptotic member of the Bcl-2 family) are overexpressed
      in HIV-1 carriers; (iii) in vitro, p53 and/or PUMA are rate-limiting for the
      induction of cell death by HIV-1 infection or, in particular, by the HIV-1
      Envelope (Env), in a variety of model systems, including the apoptosis of
      syncytia elicited by Env or cell death induced by the Env constituent gp120.
      Thus, p53 may constitute a novel therapeutic target for the treatment of AIDS.

PMID- 15865926
TI  - Regulation of the p73 protein stability and degradation.
AB  - p73, a homologue to the tumor suppressor gene p53, is involved in tumorigenesis,
      though its specific role remains unclear. The gene has two distinct promoters
      which allow the formation of two protein isoforms with opposite effects: full
      length transactivating (TA) p73 shows pro-apoptotic effects, while the shorter
      DeltaNp73, which lacks the N-terminal transactivating domain, has an evident anti
      apoptotic function. Unlike p53, the p73 gene is rarely mutated in human cancers.
      However, alterations in the relative levels of TA and DeltaNp73 have been shown
      to correlate with prognosis in several human cancers, suggesting that the fine
      regulation of these two isoforms is of pivotal importance in controlling
      proliferation and cell death. Much effort is currently focused on the elucidation
      of the mechanisms that differentially control TA and DeltaNp73 activity and
      protein stability, a process complicated by the finding that both proteins are
      regulated by a similar suite of complex post-translational modifications that
      include ubiquitination, sequential phosphorylation, prolyl-isomerization,
      recruitment into the PML-nuclear body (PML-NB), and acetylation. Here we shall
      consider the main regulatory partners of p73, with particular attention to the
      recently discovered Itch- and Nedd8-mediated degradation pathways, along with the
      emerging roles of PML, p38 MAP kinase, Pin1, and p300 in p73 transcriptional
      activation, and possible mechanisms for the differential regulation of the TAp73
      and DeltaNp73 isoforms.

PMID- 15865927
TI  - p73 induces apoptosis by different mechanisms.
AB  - p73, like its homologue, the tumor suppressor p53, is able to induce apoptosis in
      several cell types. This property is important for the involvement of p73 in
      cancer development and therapy. However, in contrast with p53, the TAp73 gene has
      two distinct promoters coding for two protein isoforms with opposite effects:
      while the transactivation proficient TAp73 shows pro-apoptotic effects, the amino
      terminal-deleted DeltaNp73 has an anti-apoptotic function. Indeed, the relative
      expression of these two proteins is related to the prognosis of several cancers.
      Here we discuss recent developments in the control of p73-induced apoptosis.
      First, TAp73 induces ER stress via the direct transactivation of Scotin. Second,
      TAp73 induces the mitochondrial pathway by directly transactivating both Bax and
      the BH3 only protein PUMA promoters. While the first transactivation is weak, and
      not sufficient to trigger apoptosis (at least in the in vitro cellular models so
      far evaluated), the induction of PUMA is strong and lethal. Third, the promoter
      of the death receptor CD95 contains a p53 responsive element and preliminary
      experiments suggest that TAp73 also activates the death receptor pathway. In
      addition, TAp73 is able to transactivate its own second promoter, thus inducing
      the expression of the anti-apoptotic DeltaNp73 isoform. Therefore, the balance
      between TAp73 and DeltaNp73 finely regulates cellular sensitivity to death.

PMID- 15865928
TI  - The role of p53 in hypoxia-induced apoptosis.
AB  - Hypoxia represents one of the most physiologically relevant stresses, having
      significant roles in both normal development and malignant progression. Exposure
      to severe hypoxia leads to the accumulation of p53 which can in turn lead to
      rapid apoptosis. In contrast to the response to DNA-damaging agents, hypoxia
      induced p53 has little or no transcriptional transactivation capabilities and
      instead seems to function primarily as a transrepressor in order to induce
      apoptosis.

PMID- 15865929
TI  - Prospective therapeutic applications of p53 inhibitors.
AB  - p53, in addition to being a key cancer preventive factor, is also a determinant
      of cancer treatment side effects causing excessive apoptotic death in several
      normal tissues during cancer therapy. p53 inhibitory strategy has been suggested
      to protect normal tissues from chemo- and radiotherapy, and to treat other
      pathologies associated with stress-mediated activation of p53. This strategy was
      validated by isolation and testing of small molecule p53 inhibitor pifithrin
      alpha that demonstrated broad tissue protecting capacity. However, in some normal
      tissues and tumors p53 plays protective role by inducing growth arrest and
      preventing cells from premature entrance into mitosis and death from mitotic
      catastrophe. Inhibition of this function of p53 can sensitize tumor cells to
      chemo- and radiotherapy, thus opening new potential application of p53 inhibitors
      and justifying the need in pharmacological agents targeting specifically either
      pro-apoptotic or growth arrest functions of p53.

PMID- 15865930
TI  - C-Abl as a modulator of p53.
AB  - P53 is renowned as a cellular tumor suppressor poised to instigate remedial
      responses to various stress insults that threaten DNA integrity. P53 levels and
      activities are kept under tight regulation involving a complex network of
      activators and inhibitors, which determine the type and extent of p53 growth
      inhibitory signaling. Within this complexity, the p53-Mdm2 negative auto
      regulatory loop serves as a major route through which intra- and extra-cellular
      stress signals are channeled to appropriate p53 responses. Mdm2 inhibits p53
      transcriptional activities and through its E3 ligase activity promotes p53
      proteasomal degradation either within the nucleus or following nuclear export.
      Upon exposure to stress signals these actions of Mdm2 have to be moderated, or
      even interrupted, in order to allow sufficient p53 to accumulate in an active
      form. Multiple mechanisms involving a variety of factors have been demonstrated
      to mediate this interruption. C-Abl is a critical factor that under physiological
      conditions is required for the maximal and efficient accumulation of active p53
      in response to DNA damage. C-Abl protects p53 by antagonizing the inhibitory
      effect of Mdm2, an action that requires a direct interplay between c-Abl and
      Mdm2. In addition, c-Abl protects p53 from other inhibitors of p53, such as the
      HPV-E6/E6AP complex, that inhibits and degrades p53 in HPV-infected cells.
      Surprisingly, the oncogenic form of c-Abl, the Bcr-Abl fusion protein in CML
      cells, also promotes the accumulation of wt p53. However, in contrast to the
      activation of p53 by c-Abl, its oncogenic form, Bcr-Abl, counteracts the growth
      inhibitory activities of p53 by modulating the p53-Mdm2 loop. Thus, it appears
      that by modulating the p53-Mdm2 loop, c-Abl and its oncogenic forms critically
      determine the type and extent of the cellular response to DNA damage.

PMID- 15865931
TI  - Mdmx as an essential regulator of p53 activity.
AB  - The murine double minute 2 (Mdm2) is a critical negative regulator of the p53
      tumor suppressor. Almost 10 years ago, a search for new p53-interactors revealed
      the existence of an Mdm2-structurally related protein, Mdmx (or Mdm4). Since then
      a large body of biochemical data has accumulated on the functions of Mdmx, often
      leading to conflicting molecular models. Nevertheless, virtually all these data
      pointed toward a critical role for Mdmx in the regulation of the p53-Mdm2
      network. A view that was recently confirmed by genetic studies. This review is a
      summary of our current understanding of this molecule, its structure and
      biological functions, as well as its relationship to its known binding partners.

PMID- 15865932
TI  - p53 in neuronal apoptosis.
AB  - The tumor suppressor and transcription factor p53 is a key modulator of cellular
      stress responses, and activation of p53 can trigger apoptosis in many cell types
      including neurons. Apoptosis is a form of programmed cell death that occurs in
      neurons during development of the nervous system and may also be responsible for
      neuronal deaths that occur in neurological disorders such as stroke, and
      Alzheimer's and Parkinson's diseases. p53 production is rapidly increased in
      neurons in response to a range of insults including DNA damage, oxidative stress,
      metabolic compromise, and cellular calcium overload. Target genes induced by p53
      in neurons include those encoding the pro-apoptotic proteins Bax and the BH3-only
      proteins PUMA and Noxa. In addition to such transcriptional control of the cell
      death machinery, p53 may more directly trigger apoptosis by acting at the level
      of mitochondria, a process that can occur in synapses (synaptic apoptosis).
      Preclinical data suggest that agents that inhibit p53 may be effective
      therapeutics for several neurodegenerative conditions.

PMID- 15865934
TI  - Death squads enlisted by the tumour suppressor p53.
AB  - p53 is a tumour suppressor that is found mutated or functionally inactivated in
      more than half of all human cancers. p53 function is activated by DNA damage,
      hypoxia, expression of certain oncogenes, and many cytotoxic stimuli. p53 is a
      transcription factor that regulates expression of target genes which promote
      apoptotic cell death, cell cycle arrest, cellular senescence, and some other
      processes. In this review we summarise current knowledge of p53 target genes
      implicated in apoptosis signalling.

PMID- 15865933
TI  - The p53 response: emerging levels of co-factor complexity.

PMID- 15865935
TI  - The multiple roles of p53 in the pathogenesis of HIV associated dementia.
AB  - The mechanism by which infection with the human immunodeficiency virus (HIV)
      leads to injury and dysfunction within the central nervous system (CNS) is not
      completely understood. Most studies support the hypothesis that neurons are
      impacted as bystander cells in a tissue environment made hostile by the innate
      and adaptive immune responses to chronic HIV infection within CNS tissue. The
      tumor suppressor transcription factor p53 participates in multiple cellular
      processes within the HIV infected CNS, and experimental evidence suggests that
      the resulting neurodegeneration occurs by induction of p53-mediated apoptotic
      pathways. Here we review the evidence for p53 as a participant in the responses
      of multiple CNS cell types to the presence of HIV and propose the hypothesis that
      HIV induced alterations in the CNS extracellular milieu converge at neuronal p53
      activation.

PMID- 15865937
TI  - Molecular interaction map of the p53 and Mdm2 logic elements, which control the
      Off-On switch of p53 in response to DNA damage.
AB  - The molecular network that controls responses to genotoxic stress is centered at
      p53 and Mdm2. Recent findings have shown this network to be more complex than
      previously envisioned. Using a notation specifically designed for circuit diagram
      like representations of bioregulatory networks, we have prepared an updated
      molecular interaction map of the immediate connections of p53 and Mdm2, which are
      described as logic elements of the network. We use the map as the basis for a
      comprehensive review of current concepts of signal processing by these logic
      elements (an interactive version of the maps-eMIMs can be examined at ). We also
      used molecular interaction maps to propose a p53 Off-On switch in response to DNA
      damage.

PMID- 15865936
TI  - Fenretinide: a p53-independent way to kill cancer cells.
AB  - The synthetic retinoid fenretinide [N-(4 hydroxyphenyl)retinamide] induces
      apoptosis of cancer cells and acts synergistically with chemotherapeutic drugs,
      thus providing opportunities for novel approaches to cancer therapy. The upstream
      signaling events induced by fenretinide include an increase in intracellular
      levels of ceramide, which is subsequently metabolized to GD3. This ganglioside
      triggers the activation of 12-Lox (12-lipoxygenase) leading to oxidative stress
      and apoptosis via the induction of the transcription factor Gadd153 and the Bcl-2
      family member protein Bak. Increased evidence suggests that the apoptotic pathway
      activated by fenretinide is p53-independent and this may represent a novel way to
      treat tumors resistant to DNA-damaging chemotherapeutic agents. Therefore,
      fenretinide offers increased clinical benefit as a novel agent for cancer
      therapy, able to complement the action of existing chemotherapeutic treatment
      regimes. Furthermore, synergy between fenretinide and chemotherapeutic drugs may
      facilitate the use of chemotherapeutic drugs at lower concentrations, with
      possible reduction in treatment-associated morbidity.

PMID- 15865938
TI  - Maintaining appearances--the role of p53 in adult neurogenesis.
AB  - In the adult mammalian brain, neuronal turnover continues to replenish cells in
      existing neuronal circuits, such as those involved either in odor discrimination
      or in learning and memory, throughout life. With age, however, the capacity for
      neurogenesis diminishes and these functions become impaired. Neuronal turnover is
      a two-step process, which first generates excess neuronal progenitors and then
      eliminates all but the few that differentiate into fully functional neurons. This
      process requires a fine balance between cell proliferation and cell death.
      Altered activity of the tumor suppressor p53 can upset this balance by affecting
      the rate of cell proliferation, but not the rate of cell death, in neurogenic
      regions of the adult brain. Genetically engineered mice in which p53 activity is
      increased demonstrate that premature loss of neurogenic capacity is linked to
      accelerated organismal aging.

PMID- 15865939
TI  - p53 mutation heterogeneity in cancer.
AB  - The p53 gene is inactivated in about 50% of human cancers and the p53 protein is
      an essential component of the cell response induced by genotoxic stresses such as
      those generated by radiotherapy or chemotherapy. It is therefore highly likely
      that these alterations are an important component in tumor resistance to therapy.
      The particular characteristics of these alterations, 80% of which are missense
      mutations leading to functionally heterogeneous proteins, make p53 a unique gene
      in the class of tumor suppressor genes. A considerable number of mutant p53
      proteins probably have an oncogenic activity per se and therefore actively
      participate in cell transformation. The fact that the apoptotic and
      antiproliferative functions of p53 can be dissociated in certain mutants also
      suggests another level of complexity in the relationships between p53
      inactivation and neoplasia.

PMID- 15865940
TI  - Stress-induced p53 runs a transcription-independent death program.
AB  - The transcription-independent p53-mediated apoptotic response has obtained a
      solid mechanistic basis in recent years. A fraction of stress-induced wild type
      p53 protein rapidly translocates to mitochondria in response to genotoxic,
      hypoxic, and oxidative stresses in established cell lines and primary cells, as
      well as in physiological and pathophysiologic stress responses in the animal.
      While the groundwork of mechanisms and kinetics of direct mitochondrial p53
      activities is laid out, the quantitative contribution of this pathway to total
      p53-mediated apoptosis and tumor suppression in vivo remains to be elucidated. An
      update on these efforts is given here.

PMID- 15865941
TI  - The transcriptional targets of p53 in apoptosis control.
AB  - Induction of apoptosis is an essential function of p53 as a tumor suppressor. p53
      can activate its downstream targets in a sequence specific manner to induce
      apoptosis. Most tumor derived p53 mutants are deficient in transcription
      activation as well as apoptosis induction. p53 can activate genes in the
      extrinsic and intrinsic pathways through transcription-dependent mechanisms or
      induce apoptosis through transcription-independent mechanisms. Several
      proapoptotic Bcl-2 family proteins, such as PUMA and Noxa, are shown to be
      critical mediators of p53-dependent apoptosis. The selective activation of the
      apoptotic targets of p53 is modulated by transcription coactivators. The
      induction of apoptotic genes alone sometimes is not sufficient to induce
      apoptosis, as the cell cycle arrest mediated by the cell cycle inhibitors
      dominates apoptosis. Preventing the induction of p21 under these conditions can
      drive the cells towards apoptosis. Understanding how p53 controls apoptosis
      through its targets may lead to discoveries of novel therapeutics to combat
      cancer and other diseases.

PMID- 15865942
TI  - Caspase-2 function in response to DNA damage.
AB  - Caspase-2 is one of the best conserved caspases across species. This enzyme is
      unique among caspases in that it has features of both initiator and effector
      caspases. Caspase-2 appears to be necessary for the onset of apoptosis triggered
      by several insults, including DNA damage, administration of TNF, and different
      pathogens and viruses. In several experimental systems, a link has been shown
      between the p53 family proteins and caspase-2 activation leading to cell death.
      In this review, current knowledge concerning the structure of this protease and
      its function in cell physiology and cell death, particularly cell death triggered
      by DNA damage, is summarized and discussed.

PMID- 15865943
TI  - The role of p53 in treatment responses of lung cancer.
AB  - Resistance to radio- and chemotherapy is a major problem in treatment responses
      of lung cancer. In this disease, biological markers, that can be predictive of
      response to treatment for guiding clinical practice, still need to be validated.
      Radiotherapy and most chemotherapeutic agents directly target DNA and in response
      to such therapies, p53 functions as a coordinator of the DNA repair process, cell
      cycle arrest, and apoptosis. In fact, it participates in the main DNA repair
      systems operative in cells, including NHEJ, HRR, NER, BER, and MMR. Given the
      high p53 mutation frequency in lung cancer which likely impairs some of the p53
      mediated functions, a role of p53 as a predictive marker for treatment responses
      has been suggested. In this review, we summarize the conflicting results coming
      from preclinical and clinical studies on the role of p53 as a predictive marker
      of responses to chemotherapy or radiotherapy in lung cancer.

PMID- 15865944
TI  - Pathways connecting telomeres and p53 in senescence, apoptosis, and cancer.
AB  - The ends of eukaryotic chromosomes are protected by specialized structures termed
      telomeres that serve in part to prevent the chromosome end from activating a DNA
      damage response. However, this important function for telomeres in chromosome end
      protection can be lost as telomeres shorten with cell division in culture or in
      self-renewing tissues with advancing age. Impaired telomere function leads to
      induction of a DNA damage response and activation of the tumor suppressor protein
      p53. p53 serves a critical role in enforcing both senescence and apoptotic
      responses to dysfunctional telomeres. Loss of p53 creates a permissive
      environment in which critically short telomeres are inappropriately joined to
      generate chromosomal end-to-end fusions. These fused chromosomes result in cycles
      of chromosome fusion-bridge-breakage, which can fuel cancer initiation,
      especially in epithelial tissues, by facilitating changes in gene copy number.

PMID- 15865945
TI  - Possible interactive effects of demographic factors and stress coping mechanisms
      on depression and anxiety in maintenance hemodialysis patients.
AB  - OBJECTIVE: The aim of this study was to assess the possible interactive effects
      of age, sex, duration of hemodialysis (HD), educational and income levels, and
      stress coping mechanisms on depression and anxiety in patients on maintenance HD.
      METHODS: Uremic patients (N=416), regularly undergoing HD for more than 1 year,
      who did not have apparent cerebrovascular disease or serious intellectual
      impairment, were investigated. The interactive effects of age, sex, duration of
      HD, and educational and income levels, in relation to stress coping mechanisms,
      on depression or anxiety were assessed by hierarchical multiple regression
      analyses. RESULTS: Regression lines illustrating significant (P<.05) interactions
      were constructed. The decrease in depression accompanying the increase in task
      oriented stress coping was greater in highly educated patients than it was in the
      other patients. Anxiety levels decreased when patients had both high income and
      demonstrated a range of task-oriented stress coping mechanisms. For patients
      undergoing HD for long duration, or with a relatively high income, the decrease
      of depression and anxiety accompanying a decrease of emotion-oriented stress
      coping was greater, as compared with other patients. The decrease of depression
      accompanying an increase of avoidance-oriented stress coping was greater in
      patients with low income and in older patients than it was in the other patients.
      CONCLUSIONS: These findings may lead to the development of specific and focused
      interventions for depression or anxiety in maintenance HD patients.

PMID- 15865946
TI  - Stress, appraisal, and coping: a comparison of HIV-infected women in the pre
      HAART and HAART eras.
AB  - BACKGROUND: It has been widely suggested that highly active antiretroviral
      therapy (HAART) has improved the psychosocial aspects of living with HIV/AIDS.
      METHOD: A sample of 79 women living with HIV/AIDS in the pre-HAART era (1994
      1996) were compared with a matched sample of 79 women with HIV/AIDS from the
      HAART era (2000-2003) on measures of stress, illness appraisals, and coping
      strategies. RESULTS: Contrary to expectations, HIV-infected women in the HAART
      era were significantly more likely than women in the pre-HAART era to report
      health-related stress, to report stress from stigma and disclosure, to view HIV
      as having caused them harm, to report that their health is due to chance, and to
      report more use of maladaptive forms of coping (e.g., escape-avoidant coping).
      CONCLUSION: Although HAART may have extended survival for many HIV-infected
      individuals, they have not resulted in equivalent psychosocial improvements.
      Thus, efforts are needed to address the psychosocial difficulties that HIV
      infected women in the HAART era continue to experience.

PMID- 15865947
TI  - Complicated grief as a stress response disorder: evaluating diagnostic criteria
      in a German sample.
AB  - BACKGROUND: Complicated grief has been described as a diagnosis candidate for DSM
      V. On the basis of the stress response theory, Horowitz et al. [Am J Psychiatry
      154 (1997) 904-10] characterized complicated grief as a combination of sustained
      intrusion, avoidance, and maladaptation symptoms following the loss of a close
      person. This study aimed at evaluating diagnostic criteria based on the stress
      response model of complicated grief. METHODS: We administered a symptom list
      derived from Horowitz et al.'s operationalization to a sample of bereaved persons
      and evaluated the psychometric properties of the symptom criteria and symptom
      category subscales. Using this symptom list and other self-report measures of
      psychopathology and normal grief reactions, we examined a German sample
      consisting of 75 participants who had lost either siblings, children, parents, or
      spouses, on average, 5.4 years prior to the study. RESULTS: Analyses confirmed
      the classification of symptoms into intrusion, avoidance, and failure-to-adapt
      categories with only minimal reordering (two symptom criteria). The symptom
      category subscales showed favourable psychometric characteristics, receiver
      operating characteristic (ROC) analyses indicated high diagnostic accuracy of the
      symptom criteria, and predictive validation revealed a meaningful correlational
      pattern to standard measures of divergent psychopathology and normal grief
      reactions. CONCLUSIONS: The application of a stress response operationalization
      of complicated grief is supported.

PMID- 15865948
TI  - Extending the demand-control model to informal caregiving.
AB  - OBJECTIVE: Karasek's demand-control model of job strain was used in an attempt to
      extend previous work examining the psychological impact of informal caregiving in
      stroke. METHOD: Data were gathered from 138 informal caregivers/patient dyads at
      two time points. The dependent variables were the caregiver's anxiety and
      depression [Hospital Anxiety and Depression Scale (HADS)]. The predictor
      variables were caregiver demand (stroke survivor's assessment of their physical
      and psychosocial functional limitations) and control (caregiver's perceived
      control over stroke survivor's recovery). RESULTS: In a cross-sectional analysis
      of Times 1 and 2 data, main effects for demand and/or control were detected for
      anxiety and depression. Contrary to prediction, in longitudinal analysis of
      change, it was found that decreasing control, along with increasing demand, was
      associated with reduced distress. CONCLUSION: The model was moderately successful
      in predicting emotional distress. The relative importance of caregiver demand and
      control in predicting outcomes changed over time in these data. Attempts to
      replicate these findings are recommended.

PMID- 15865949
TI  - Do others really know us better? Predicting migraine activity from self- and
      other-ratings of negative emotion.
AB  - OBJECTIVE: The validity of self-reported negative emotion to predict health
      status is limited by response biases, introspection limitations, and
      methodological confounds. The reports of significant others about the patients'
      negative emotion may circumvent these limitations. This study sought to compare
      the validity of self- versus other-reported negative emotion as a correlate of
      migraine headache activity. METHODS: On 89 patients with migraine headache (74
      women and 15 men), we correlated self-ratings and significant-other-ratings of
      patients' negative emotion with patients' report of migraine frequency and
      severity, which were assessed both cross-sectionally and prospectively, 3 months
      later. RESULTS: Other-reported negative emotion correlated with migraine activity
      better than did self-reported negative emotion, both cross-sectionally and
      prospectively. Patterns were different for women and men, however. Among women,
      other-reported negative emotion was positively associated with migraine activity.
      Among men, other-reported negative emotion was inversely associated with migraine
      frequency and severity. CONCLUSION: The results suggest that it may be valuable
      to obtain significant-other-ratings when assessing negative emotion in patients
      and that the genders may differ in how others' ratings are related to the
      patients' health.

PMID- 15865950
TI  - Psychiatric comorbidity in gender identity disorder.
AB  - OBJECTIVE: Despite being recognized as an important prognostic factor for the
      outcome in gender identity disorder (GID), psychiatric comorbidity has rarely
      been assessed by means of standardized diagnostic instruments. The aim of this
      study was to assess current and lifetime psychiatric comorbidity in patients with
      GID. METHODS: A cross-sectional sample of 31 patients who were treated for GID
      was assessed by the structured clinical interview for Axis I and II (SCID-I/II)
      and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Twenty-nine
      percent of the patients had no current or lifetime Axis I disorder; 39% fulfilled
      the criteria for current and 71% for current and/or lifetime Axis I diagnosis.
      Forty-two percent of the patients were diagnosed with one or more personality
      disorders. CONCLUSIONS: Lifetime psychiatric comorbidity in GID patients is high,
      and this should be taken into account in the assessment and treatment planning of
      GID patients.

PMID- 15865951
TI  - Memory beliefs and function in fibromyalgia patients.
AB  - OBJECTIVE: The aim of this study was to investigate memory beliefs and their
      relationship to actual memory function in fibromyalgia (FM) patients. METHODS:
      Twenty-three FM patients, 23 age- and education-matched controls, and 22 older
      controls completed the Metamemory in Adulthood (MIA) questionnaire, which
      assessed beliefs about seven aspects of memory function. Group differences on the
      seven scales were assessed, and scores on the capacity scale were correlated with
      objective memory performance. RESULTS: FM patients reported lower memory capacity
      and more memory deterioration than did either control group. Patients reported
      lower control or self-efficacy over memory, higher achievement motivation, higher
      strategy use, and higher anxiety about memory than age-matched controls did.
      Among the patients, perceived capacity, achievement motivation, and self-efficacy
      were significantly correlated with objective memory performance on a recall task.
      CONCLUSION: FM patients' complaints about memory function have some accuracy.

PMID- 15865952
TI  - Family studies in insomnia.
AB  - OBJECTIVE: Several predisposing factors to insomnia have been hypothesized,
      including a familial component; however, few studies have focused on this topic.
      The aim of this study is to evaluate the prevalence of insomnia among first
      degree relatives of chronic insomniacs and to compare the symptoms between
      sporadic and familial insomnia. METHODS: Two hundred fifty-six consecutive
      chronic insomniacs completed a clinical interview, psychometric questionnaires, a
      questionnaire on the family history of insomnia and, when indicated, a
      polysomnography. A control group was performed to estimate a base-rate incidence
      of insomnia in their families. RESULTS: Patients with primary (n=77) and
      psychiatric (n=104) insomnia were definitely included. Of those with primary
      insomnia, 72.7% reported familial insomnia compared with 24.1% in the noninsomnia
      control group. Among the psychiatric insomniacs, 43.3% reported familial
      insomnia. The mother was the relative most frequently affected. Comparisons
      between the family prevalence rates of insomnia assessed by the probands and by
      first-degree relatives show high concordance. A tendency to a younger age at
      onset was observed in familial and primary insomnia. CONCLUSION: This study
      reports a significant increase of familial aggregation of insomnia, warranting
      further genetic studies in primary insomnia with early age at onset.

PMID- 15865953
TI  - Adult attachment, alexithymia, and symptom reporting: an extension to the four
      category model of attachment.
AB  - OBJECTIVE: A previous study using a three-category attachment model found that
      avoidant attachment was associated with increased symptom reporting, and that
      this relationship was largely mediated by negative affectivity and alexithymia.
      The present study aimed to advance on these findings by using a four-category
      model of attachment to determine which aspect of avoidant attachment (fearful or
      dismissing) is related to symptom reporting, and via which mediating variables.
      METHOD: One hundred and forty-two male and female undergraduates, aged 17-44,
      completed questionnaire measures of attachment style, alexithymia, self-esteem,
      positive and negative affectivity, and symptom reporting. RESULTS: Fearful and
      preoccupied attachment styles, negative affectivity, and alexithymia were all
      significantly associated with increased symptom reporting, while the dismissing
      attachment style was not. Regression analyses showed that the relationship
      between fearful attachment and symptom reporting was partly, but not fully,
      mediated by alexithymia and negative affectivity, while that between preoccupied
      attachment and symptom reporting was mediated mainly by negative affectivity. Low
      self-esteem was associated with symptom reporting only via its association with
      negative affectivity. CONCLUSIONS: Fearful and preoccupied attachment styles are
      both associated with symptom reporting via a negative model of the self and
      increased negative affectivity, but alexithymia is an additional predictor of
      symptom reporting in individuals with fearful attachment. This difference is
      thought to be linked to the model of others developed in early interactions with
      caregivers.

PMID- 15865954
TI  - Assessing the reliability and validity of the Bermond-Vorst Alexithymia
      Questionnaire among U.S. Anglo and U.S. Hispanic samples.
AB  - OBJECTIVE: The aim of this paper is to assess the psychometric properties of the
      Bermond-Vorst Alexithymia Questionnaire (BVAQ) in U.S. Anglo and U.S. Hispanic
      samples of college students. METHOD: One hundred ninety-four U.S. Hispanics and
      304 U.S. Anglos participated in the study. In addition to completing the BVAQ,
      participants completed the 20-item Toronto Alexithymia Scale (TAS-20), the Beck
      Depression Inventory (BDI), and the Eysenck Neuroticism Scale (ENS). RESULTS:
      BVAQ and TAS-20 subscales were correlated across groups. While the identifying
      and verbalizing composites of the BVAQ subscales were predictive of neuroticism
      and depression across groups in the expected direction, the fantasizing subscale
      of the BVAQ was negatively predictive of depression and neuroticism across
      groups. CONCLUSION: Given the unexpected findings associated with some of the
      BVAQ subscales, future research should explore the dimensionality of alexithymia.

PMID- 15865955
TI  - Psychometric properties of the Toronto Alexithymia Scale (TAS-20) for substance
      users.
AB  - OBJECTIVE: To determine the psychometric properties of the Toronto Alexithymia
      Scale (TAS-20), an established self-report measure of alexithymia, for a
      substance user sample participating in a clinical trial of outpatient cognitive
      behavioral therapies (N=230). METHODS: Confirmatory and exploratory factor
      analyses were used to determine the number and nature of the factors underlying
      the TAS-20 in a sample of substance users. Structural equation modeling was used
      to determine the predictive validity of the TAS-20. RESULTS: A factor structure
      comparable, but not identical, with TAS-20 psychometric results with other
      populations was found; alpha coefficients were .88 for the feelings factor, .62
      for the external thinking factor, and .87 for the total score. Although, on
      average, the substance users did not appear to have elevated alexithymia scores
      compared with the undergraduate students, alexithymia predicted less treatment
      engagement, i.e., fewer sessions attended and weaker helping alliance.
      Alexithymia also predicted alcohol use outcomes but not drug use outcomes. The
      relation between alexithymia and drinking outcome was conditional on whether the
      patient was using solely alcohol at baseline. CONCLUSION: The TAS-20 has
      reasonably good psychometric properties in this sample, which might be improved
      by dropping several marginal questionnaire items. Alexithymia appears to
      attenuate substance abuse treatment engagement. More clinical and research
      experience with this construct and specific instrument in substance user samples
      is needed.

PMID- 15865957
TI  - Isolation of DNA from plants with large amounts of secondary metabolites.
AB  - Many plant species have high contents of polysaccharides, polyphenols, or other
      secondary metabolites that can interfere with DNA extraction and purification.
      These contaminating compounds can lead to poor DNA yield and prevent access by
      modifying enzymes, such as restriction endonucleases and Taq polymerase. A number
      of factors, including choice of plant tissue, tissue preparation, and
      modifications of the extraction buffer, can help in DNA extraction for difficult
      plant species. This chapter presents some of the DNA extraction protocols
      developed for various plants.

PMID- 15865958
TI  - Nucleic acid isolation from environmental aqueous samples.
AB  - The application of molecular techniques has revolutionized freshwater and marine
      ecology, especially for plankton research. Methods, such as denatured gradient
      gel electrophoresis (DGGE), temperature gradient gel electrophoresis (TGGE), and
      single-strand conformation polymorphism (SSCP), together with environmental clone
      libraries, have unraveled an unexpected biodiversity of organisms in the water
      column. Molecular probes are just entering the field of commercialization for
      monitoring toxic algal blooms. Genomics and metagenomics were recently introduced
      into marine biology. At the basis of all molecular approaches is the isolation of
      nucleic acids from cultures, tissue, or environmental samples. Here, we summarize
      methods, quality controls, and hints for sample treatment to reliably isolate
      nucleic acids, both DNA and RNA, from environmental aqueous samples. This chapter
      not only is directed to researchers inexperienced with such methods but also is
      an aid to those already working in the field. It may be used as a step-by-step
      guide for nucleic acid isolation from field samples, and we make suggestions for
      subsequent use of the DNA/RNA.

PMID- 15865959
TI  - Nucleic acid isolation from ecological samples--vertebrate gut flora.
AB  - The utility of DNA molecules in identifying and characterizing intestinal
      microorganisms depends on methods that facilitate access to DNA of sufficient
      purity, quantity, and integrity. An efficient and unbiased extraction of DNA is
      thus critical to the validity of the subsequent analysis of the prevalence and
      diversity of the DNA sources in the sample. The highly heterogeneous composition
      of the diet of vertebrates makes DNA isolation challenging for this environment.
      Here, we consider the key steps involved in DNA isolation from vertebrate gut
      microflora including sample homogenization, lysis of bacterial cells, and
      extraction and precipitation of DNA. A detailed protocol for DNA isolation of the
      microbial contents of intestine and feces is also provided. In addition, we refer
      to commercially available methods for DNA extraction from the vertebrate gut
      flora.

PMID- 15865960
TI  - Nucleic acid isolation from ecological samples--fungal associations, lichens.
AB  - Ecological samples of fungal associations pose particular challenges for nucleic
      acid extraction due to the presence of several genomes. Thorough examination of
      the samples prior to extraction is important to assess the risks of
      contamination. If manual separation of symbionts or their axenic cultivation is
      not feasible, symbiont-specific primers can be applied in PCR experiments. A
      basic protocol is suggested here which can be optimized for specific
      applications.

PMID- 15865961
TI  - Nucleic acid isolation from ecological samples--fungal associations, mycorrhizae.
AB  - Mycorrhizal fungi are among the most common symbioses found in terrestrial
      ecosystems, both natural and managed. They are important for many reasons, but
      most notably because of their positive effects on plant growth, which are
      mediated by their uptake of nutrients from the soil and transport of these to the
      roots. Moreover, many edible fungi are mycorrhizal. The study of mycorrhizal
      fungi has been hampered by the inability to identify species and individuals in
      the soil. This has been greatly aided by DNA-based methods, which first require
      the extraction of DNA. Herein, I discuss some general concerns that must be
      considered when extracting and purifying DNA from ecological samples and offer
      specific methods for soil, mycorrhizal roots, and fruiting bodies. These methods
      are rapid, safe, effective, relatively inexpensive, and convenient because they
      are based on commercially available kits.

PMID- 15865962
TI  - Nucleic acid isolation from ecological samples--animal scat and other associated
      materials.
AB  - Noninvasive sampling is very attractive to field biologists and has tremendous
      potential for studying secretive species and being a cost-effective method of
      increasing sample sizes in studies of large, dangerous animals. Extracting DNA
      from noninvasively collected samples can be challenging, and the methods have
      been developed mainly through modification of previously developed protocols for
      other sample types. We present the most commonly used methods along with
      modifications used by some researchers to deal with the problem of coextraction
      of polymerase chain reaction (PCR) inhibitors. Although it is difficult to
      generalize about which methods should be used on particular sample types, we
      discuss the success of the methods in studies to date. We close with general
      suggestions for dealing with potential problems associated with the analysis of
      DNA obtained from noninvasively collected samples.

PMID- 15865963
TI  - Isolation and analysis of DNA from archaeological, clinical, and natural history
      specimens.
AB  - The use of ancient DNA (aDNA) in the reconstruction of population origins and
      evolution is becoming increasingly common. Novel methods exist for the isolation,
      purification, and analysis of aDNA because these DNA templates are likely to be
      damaged, fragmented and?or associated with non-nucleic acid material. However,
      contamination of ancient specimens and DNA extracts with modern DNA is more
      widespread than is generally acknowledged and remains a significant problem in
      aDNA analysis. Studies of human aDNA are uniquely sensitive to contamination due
      to the continual presence of potential contamination sources. Meticulous
      authentication of results and careful selection of polymorphic markers capable of
      distinguishing between aDNA and probable DNA contaminants are critical to a
      successful aDNA study.

PMID- 15865964
TI  - Animal phylogenomics: multiple interspecific genome comparisons.
AB  - The utility of DNA sequence information for phylogenetics and phylogeography is
      now well known. Rather than attempt to summarize studies addressing this well
      demonstrated utility, this chapter focuses on fundamental approaches and
      techniques that implement the collection of DNA sequence data for comparative
      phylogenetic purposes in a genomic context (phylogenomics). Whole genome
      sequencing approaches have changed the way we think about phylogenetics and have
      opened the way for new perspectives on "old" phylogenetics concerns. Some of
      these concerns are which gene regions to use and how much sequence information is
      needed for robust phylogenetic inference. Whole genome sequences of a few animal
      model organisms have gone a long way to implement approaches to better understand
      these important phylogenetic concerns. This chapter also addresses how genomics
      has made it more important for a clear understanding of orthology of gene regions
      in comparative biology. Finally, genome-enabled technologies that are affecting
      comparative biology are also discussed.

PMID- 15865965
TI  - ISSR techniques for evolutionary biology.
AB  - Inter-simple sequence repeat (ISSR) markers were originally devised for
      differentiating among closely related plant cultivars but have become extremely
      useful for studies of natural populations of plants, fungi, insects, and
      vertebrates. The markers are easily generated using minimal equipment and are
      hypervariable, yielding a large amount of data for a reasonable cost to the
      researcher. The methods for Miniprep DNA extraction and cleanup, polymerase chain
      reaction (PCR) amplification, optimization, data gathering and scoring, and data
      analyses are outlined.

PMID- 15865966
TI  - Use of amplified fragment length polymorphism (AFLP) markers in surveys of
      vertebrate diversity.
AB  - The amplified fragment length polymorphism (AFLP) technique is one of the most
      informative and cost-effective fingerprinting methods. It produces polymerase
      chain reaction (PCR)-based multi-locus genotypes helpful in many areas of
      population genetics. This chapter focuses on technical laboratory information to
      successfully develop the AFLP technique for vertebrates. Several AFLP protocols
      are described, as well as recommendations about important factors of the
      procedure such as the choice of enzyme and primer combinations, the choice and
      scoring of markers, the influence of the genome size on the AFLP procedure, and
      the control and estimation of genotyping errors. Finally, this chapter proposes a
      troubleshooting guide to help resolve the main technical difficulties encountered
      during the AFLP procedure.

PMID- 15865967
TI  - Use of AFLP markers in surveys of arthropod diversity.
AB  - Arthropods comprise the most diverse group of animals on earth and as such have
      been the subject of considerable evolutionary research. For example, much of our
      understanding of the genetic basis of evolutionary change is derived from the
      insect genus Drosophila, one of the most well-studied organisms in biology.
      Arthropods are also of tremendous economic importance as both providers and chief
      destroyers of food for human consumption. Thus, the genetic diversity of
      arthropods is of interest from both a pure research perspective and for practical
      economic reasons. The amplified fragment length polymorphism (AFLP) method of
      genetic analysis, developed in the early and mid-1990s (Vos et al., 1995; Zabeau,
      1992; Zabeau and Vos, 1993), offers a relatively new method for assessing genetic
      diversity and has been increasingly applied in studies of arthropods. Originally
      coined selective restriction fragment amplification (SRFA) (Zabeau and Vos,
      1993), the method was renamed (Vos et al., 1995) presumably to reflect its
      similarity to restriction fragment length polymorphism (RFLP). Since then, AFLPs
      have become a popular tool in both population genetics to estimate population
      parameters such as heterozygosity, F-statistics, migration rates, and genetic
      distances, as well as phylogenetics, to infer relationships among closely related
      taxa. In arthropods, AFLPs have been used to assess genetic variation both within
      and between species in various taxa including crustaceans, chelicerates, and
      insects, often yielding novel insights. In this chapter, we briefly describe the
      AFLP method and its strengths and limitations. We then discuss the use of AFLPs
      in surveys of arthropod diversity, highlighting the specific questions addressed
      using AFLPs. Finally, a section on experimental design and methods, based on
      research in our laboratory, is provided.

PMID- 15865968
TI  - Use of AFLP markers in surveys of plant diversity.
AB  - The collection of the available range of genetic variation in a gene pool,
      usually made of the cultivated species and their undomesticated relatives, is
      referred to as a germplasm collection. Increasingly, discriminator data generated
      using molecular genetic markers are either complementing or completely replacing
      those from morphological characters (known as descriptors) in surveys of genetic
      diversity. In addition to highlighting the state of knowledge on the specific
      applications of amplified fragment length polymorphisms (AFLPs) in surveys of
      plant genetic diversity, an attempt at a brief description and comparison of the
      different marker systems in use has also been made in this chapter. We have also
      attempted a description of the AFLP marker technology, its strengths and
      weaknesses, methodologies for generating reliable AFLP data, available resources
      (hardware, software, consumables); the kinds of questions for which AFLP data
      provide valid answers; and data management options. This chapter also highlights
      salient considerations that would guide decisions on the adoption of molecular
      marker assays.

PMID- 15865969
TI  - Isolating microsatellite DNA loci.
AB  - A series of techniques are presented to construct genomic DNA libraries highly
      enriched for microsatellite DNA loci. The individual techniques used here derive
      from several published protocols but have been optimized and tested in our
      research laboratories as well as in classroom settings at the University of South
      Carolina and University of Georgia, with students achieving nearly 100% success.
      Reducing the number of manipulations involved has been a key to success,
      decreasing both the failure rate and the time necessary to isolate loci of
      interest. In our lab during the past 3 years alone, these protocols have been
      successfully used to isolate microsatellite DNA loci from at least 55 species
      representing three kingdoms. These protocols have made it possible to reduce the
      time to identify candidate loci for primer development from most eukaryotic
      species to as little as 1 week.

PMID- 15865970
TI  - Use of microsatellites for parentage and kinship analyses in animals.
AB  - Microsatellite markers are quickly becoming the molecular marker of choice for
      studies of parentage and kinship in animals. In this chapter, we review methods
      and give protocols for screening potential microsatellite markers, as well as
      protocols for genotyping individuals with useful markers once they have been
      identified. In addition, we explain how microsatellites can be used to assess
      parentage and kinship, give basic analytical methods, and briefly review more
      sophisticated approaches that can be used to circumvent many of the problems that
      arise in any real empirical study.

PMID- 15865971
TI  - Use of capillary array electrophoresis single-strand conformational polymorphism
      analysis to estimate genetic diversity of candidate genes in germplasm
      collections.
AB  - Capillary array electrophoresis single-strand conformation polymorphism (CAE
      SSCP) analysis provides a reliable high-throughput method to genotype plant
      germplasm collections. Primers designed for highly conserved regions of candidate
      genes can be used to amplify DNA from plants in the collection. These amplified
      DNA fragments of identical length are turned into useful markers by assaying
      sequence differences by CAE-SSCP analysis. Sequence differences affect the
      electrophoretic mobility of single-stranded DNA under non-denaturing conditions.
      By collecting the mobility data for both strands assayed at two temperatures,
      alleles can be defined by mobility alone. For a germplasm collection with an
      unknown number of alleles at a locus, such mobility data of homozygotes can be
      used to determine the number of unique alleles without the necessity of cloning
      and sequencing each allele.

PMID- 15865972
TI  - Ribosomal RNA probes and microarrays: their potential use in assessing microbial
      biodiversity.
AB  - The awareness that global biological diversity is affected by numerous, mostly
      human-made threats has made biodiversity assessment an important scientific issue
      for decades. Biodiversity includes different levels of complexity, such as
      community diversity, habitat diversity, genetic diversity, and species diversity.
      The application of molecular methods to answer ecological questions permits
      issues of biodiversity to be addressed at all levels. Microorganisms dominate
      global biological diversity in terms of their species numbers. However, their
      small size and limited morphological features make it challenging to obtain a
      comprehensive view of their biodiversity. The application of ribosomal RNA (rRNA)
      probes contributes significantly to the assessment of biodiversity at the
      molecular level. DNA microarrays offer a great potential to facilitate the
      application of molecular probes and other DNA analytical methods to answer
      ecological and biodiversity questions. We provide an introduction into the
      application of rRNA probes and DNA microarrays for the assessment of microbial
      biodiversity, as well as protocols for the implementation of DNA microarrays.

PMID- 15865973
TI  - The role of geographic analysis in locating, understanding, and using plant
      genetic diversity.
AB  - The genetic structure of an organism is shaped by various factors, many of which
      vary significantly over space. In this chapter, we provide insight on how
      studying geographic patterns may contribute to an improved understanding of
      variability in genetic structure. We first review the theoretical background on
      how differences in genetic structure may be generated through processes that are
      inherently variable over space. We then present novices with some basics on how
      geographic information systems (GIS) may be adopted to study this variation,
      including advice on software, data, and the type of research questions that might
      be addressed. The chapter finishes with a brief review of how spatial analysis
      has contributed to the conservation and use of plant genetic resources, through
      an understanding of spatial patterns in species distribution and genetic
      structure. We conclude that spatial variation is a factor often overlooked in
      genetic studies and one that merits greater consideration. With the advent of
      functional genomics and improved quantification of adaptive traits, spatial
      analysis may be key in understanding variation in genetic structure through
      careful analysis of genotype-environment interactions.

PMID- 15865974
TI  - In situ hybridization of phytoplankton using fluorescently labeled rRNA probes.
AB  - Phytoplankton are one of the major components of ecosystem processes and play an
      important role in many biogeochemical cycles in the marine and freshwater
      environment. Despite their importance, many microalgae are poorly described and
      little is known of broad spatial and temporal scale trends in their abundance and
      distribution. Reasons for this are that microalgae are often small, lack distinct
      morphological features, and are unculturable, which make analyses difficult. It
      is now possible by using molecular biological techniques to advance our knowledge
      of aquatic biodiversity and to understand how biodiversity supports ecosystem
      structure, dynamics, and resilience. We present in this chapter a brief review of
      the progress that has been made in analyzing microalgae from populations to the
      species level. The described methods range from DNA fingerprinting techniques,
      such as random amplified polymorphic DNA (RAPD), amplified fragment length
      polymorphisms (AFLPs), and simple sequence repeats (SSRs), to microsatellites,
      which are used in population studies, to sequence analysis, which help to
      reconstruct the evolutionary history of organisms and to examine relationships at
      various taxonomic levels. Special emphasis is given to the application of
      molecular probes for the identification and characterization of microalgal taxa.
      The fast and secure identification of phytoplankton, especially of toxic species,
      is important from an ecological and economical point of view and whole-cell
      hybridization with specific fluorochrome-labeled probes followed by fluorescence
      microscopy or flow cytometry offers a fast method for this purpose. In this
      context, we present a detailed protocol for fluorescence in situ hybridization
      (FISH) of ribosomal RNA (rRNA) probes that can be applied to many algal cell
      types and discuss practical considerations of its use.

PMID- 15865975
TI  - Sequencing and comparing whole mitochondrial genomes of animals.
AB  - Comparing complete animal mitochondrial genome sequences is becoming increasingly
      common for phylogenetic reconstruction and as a model for genome evolution. Not
      only are they much more informative than shorter sequences of individual genes
      for inferring evolutionary relatedness, but these data also provide sets of
      genome-level characters, such as the relative arrangements of genes, which can be
      especially powerful. We describe here the protocols commonly used for physically
      isolating mitochondrial DNA (mtDNA), for amplifying these by polymerase chain
      reaction (PCR) or rolling circle amplification (RCA), for cloning, sequencing,
      assembly, validation, and gene annotation, and for comparing both sequences and
      gene arrangements. On several topics, we offer general observations based on our
      experiences with determining and comparing complete mitochondrial DNA sequences.

PMID- 15865976
TI  - Methods for obtaining and analyzing whole chloroplast genome sequences.
AB  - During the past decade, there has been a rapid increase in our understanding of
      plastid genome organization and evolution due to the availability of many new
      completely sequenced genomes. There are 45 complete genomes published and ongoing
      projects are likely to increase this sampling to nearly 200 genomes during the
      next 5 years. Several groups of researchers including ours have been developing
      new techniques for gathering and analyzing entire plastid genome sequences and
      details of these developments are summarized in this chapter. The most important
      developments that enhance our ability to generate whole chloroplast genome
      sequences involve the generation of pure fractions of chloroplast genomes by
      whole genome amplification using rolling circle amplification, cloning genomes
      into Fosmid or bacterial artificial chromosome (BAC) vectors, and the development
      of an organellar annotation program (Dual Organellar GenoMe Annotator [DOGMA]).
      In addition to providing details of these methods, we provide an overview of
      methods for analyzing complete plastid genome sequences for repeats and gene
      content, as well as approaches for using gene order and sequence data for
      phylogeny reconstruction. This explosive increase in the number of sequenced
      plastid genomes and improved computational tools will provide many insights into
      the evolution of these genomes and much new data for assessing relationships at
      deep nodes in plants and other photosynthetic organisms.

PMID- 15865977
TI  - Construction of bacterial artificial chromosome libraries for use in phylogenetic
      studies.
AB  - Bacterial artificial chromosome (BAC) libraries are emerging as valuable tools
      for investigating phylogenetic relationships at the level of genome structure. To
      date, BAC library construction has been restricted to a fairly small number of
      laboratories and species that represent a not insignificant, but a fairly small,
      fraction of diversity in the plant kingdom. This chapter is intended to
      contribute to rectifying this situation by providing protocols that facilitate
      BAC library construction in laboratories possessing basic molecular biology
      skills.

PMID- 15865978
TI  - Isolation of genes from plant Y chromosomes.
AB  - Few plant species are dioecious and only a small fraction of these species are
      known to have sex chromosomes. Considerable efforts to isolate sex-linked genes
      from dioecious Silene latifolia (Caryophillaceae) have resulted in the isolation
      of surprisingly few sex-linked genes, suggesting that the methods used previously
      were not efficient in plants. This chapter analyzes the methods that have been
      and can be used for isolation of genes from plant sex chromosomes. The most
      successful method used for the isolation of Y-linked genes included the screening
      of a male complementary DNA (cDNA) library with the probe obtained by degenerate
      oligonucleotide-primed polymerase chain reaction (PCR) of the microdissected Y
      chromosomes. However, chromosome microdissection requires sophisticated equipment
      and is difficult to apply to species with cytologically indistinguishable sex
      chromosomes. Genome and cDNA library subtraction methods were surprisingly
      unsuccessful, probably because of low divergence between the homologous X- and Y
      linked genes in plants. Segregation testing and genomics-based methods are
      increasingly popular and are the most promising approaches for isolation of
      multiple genes from plant sex chromosomes.

PMID- 15865979
TI  - Preparation of samples for comparative studies of plant chromosomes using in situ
      hybridization methods.
AB  - The development of fluorescence in situ hybridization (FISH) has led to the
      advancement of chromosome studies not only for physical mapping and genome
      analyses but also as a tool for evolutionary studies. Isolated repetitive DNA
      sequences have been useful cytological markers, but large-insert genomic
      libraries (e.g., bacterial artificial chromosomes [BACs], yeast artificial
      chromosomes [YACs], and cosmids) are being increasingly used to serve as probes
      for large segments of DNA across related genomes. Although FISH is usually
      applied to metaphase chromosomes, fiber FISH, a variation of FISH using extended
      DNA fibers, is now used to measure loci at the resolution of a few kilobases to
      compare orthologous genome segments across related genomes. A generalized set of
      protocols for chromosome preparation, FISH, and fiber FISH are presented;
      however, it is often necessary to experiment with techniques for different plant
      taxa for successful molecular cytogenetic studies.

PMID- 15865980
TI  - Preparation of samples for comparative studies of arthropod chromosomes:
      visualization, in situ hybridization, and genome size estimation.
AB  - The ability to obtain large amounts of genomic sequence for organisms and high
      throughput technology has led to a change in the thrust of research at the level
      of chromosomes in animals. In the past chromosomal analysis of animals was
      focused on gross changes such as inversions, translocations, and deletions for
      both genetic and evolutionary studies. The advent of in situ hybridization
      technology and the ability to measure genome content size changed both the
      precision and the scale of studies addressing chromosomal change as a tool in
      evolutionary biology. This chapter addresses two of the major areas of change
      that have occurred in chromosomal studies in the past decade -- examination of
      more refined and genome enabled structural changes in chromosomes and genome size
      measure. This chapter describes some of the chromosome structure approaches such
      as fluorescent in situ hybridization (FISH), comparative genomic hybridization
      (CGH) and other techniques. As well, advances in Genome size measurement and
      theory are described herein.

PMID- 15865981
TI  - Experimental methods for assaying natural transformation and inferring horizontal
      gene transfer.
AB  - The observation of frequent lateral acquisitions of genes in sequenced bacterial
      genomes has spurred experimental investigations to elucidate the factors
      governing ongoing gene transfer processes in bacteria. The uptake of naked DNA by
      natural transformation is known to occur in a wide range of bacterial species and
      in some archaea. We describe a series of protocols designed to dissect the
      natural genetic transformability of individual bacterial strains under conditions
      that progress from standard in vitro conditions to purely in situ, or natural,
      conditions. One of the most important factors in ensuring the success of any
      transformation assay system is the use of a sensitive, effective, and
      distinguishable selection regimen. Detailed template protocols for assaying
      bacterial transformation in vitro are presented using the naturally competent
      bacterium Acinetobacter baylyi strain BD413 as a model. Factors increasing the
      complexity of the assay systems are included in the following section describing
      the incorporation of components of natural systems to the in vitro models, such
      as in soil and water microcosm experiments. We then present template protocols
      for the transformation of bacteria in modified natural systems, such as in the
      presence of host tissues and extracts or in the greenhouse. Clear and
      ecologically meaningful demonstrations of in situ natural transformation are most
      desirable but are also the most complex and challenging. Because of the highly
      variable nature of these experiments, we include a discussion of important
      factors that should be considered when designing such experiments. Some
      advantages and disadvantages of the experimental systems with regard to resolving
      the hypotheses tested are included in each section.

PMID- 15865982
TI  - Use of confocal microscopy in comparative studies of vertebrate morphology.
AB  - Laser scanning confocal microscopy provides a means to acquire and analyze images
      of complex morphological structures and to help place molecules or cells of
      interest in their proper morphological context. Confocal microscopy is a form of
      fluorescence microscopy that sharpens the images collected by visualizing the
      light from only one plane of focus. This allows for the collection of multiple
      focal planes in what is called a z-stack, which provides three-dimensional data.
      Five steps that any investigator using a confocal microscope should follow are
      described: (1) labeling and (2) mounting of specimens for viewing, (3) optimizing
      the image on the confocal, and (4) collecting and (5) analyzing of confocal image
      data. We describe three specific protocols incorporating these steps from our
      work on vertebrate inner ear development. The first two describe a collection of
      z-stacks in living, fluorescently labeled, and intact embryos. The second
      protocol is for time-lapse imaging of multiple focal planes at each time point.
      The third protocol describes confocal imaging of preserved material double
      labeled with antibodies and by retrograde labeling of neurons via axonal uptake.
      Finally, three alternative or complementary approaches to standard confocal
      microscopy are described and discussed.

PMID- 15865983
TI  - PrimerSelect: a transcriptome-wide oligonucleotide primer pair design program for
      kinetic RT-PCR-based transcript profiling.
AB  - We describe PrimerSelect, a program capable of transcriptome-wide design of
      primer pairs for optimal performance in kinetic reverse-transcriptase polymerase
      chain reaction (RT-PCR). For the yeast Saccharomyces cerevisiae, PrimerSelect
      designs primer pairs for 86% of genomic open reading frames (ORFs) using design
      criteria we previously established to be optimal for kinetic RT-PCR (kRT-PCR)
      based transcript quantitation. Primer pairs designed by PrimerSelect for 230
      yeast ORFs were evaluated for primer dimer potential, PCR cyclewise yield, and
      cross-priming. Performance of 95% of these primer pairs is optimal with respect
      to primer dimer potential and PCR cyclewise yield for quantitating even the
      rarest yeast transcript. All of the primer pairs produced a single amplicon of
      the expected size from yeast genomic DNA template. The utility of PrimerSelect
      for designing primer pairs complementary to ORF sequences defined for multiple
      isolates of the human bacterial pathogens Helicobacter pylori and Staphylococcus
      aureus is also demonstrated.

PMID- 15865984
TI  - Detecting differential expression of parental or progenitor alleles in genetic
      hybrids and allopolyploids.
AB  - Three assays useful for detecting specific RNA transcripts are primer extension,
      S1 nuclease protection, and reverse-transcription-cleaved amplified polymorphic
      sequence (RT-CAPS) analysis. All three of these techniques are used routinely for
      gene expression analyses and allow insights not possible by RNA blot (northern
      blot) hybridization. In this chapter, we describe how the primer extension, S1
      nuclease protection, and RT-CAPS methods can be used to discriminate one or more
      parental or progenitor alleles in hybrids or allopolyploids. We discuss the
      rationale for using the different techniques and provide examples of the data
      generated.

PMID- 15865985
TI  - Methods for genome-wide analysis of gene expression changes in polyploids.
AB  - Polyploidy is an evolutionary innovation, providing extra sets of genetic
      material for phenotypic variation and adaptation. It is predicted that changes of
      gene expression by genetic and epigenetic mechanisms are responsible for novel
      variation in nascent and established polyploids (Liu and Wendel, 2002; Osborn et
      al., 2003; Pikaard, 2001). Studying gene expression changes in allopolyploids is
      more complicated than in autopolyploids, because allopolyploids contain more than
      two sets of genomes originating from divergent, but related, species. Here we
      describe two methods that are applicable to the genome-wide analysis of gene
      expression differences resulting from genome duplication in autopolyploids or
      interactions between homoeologous genomes in allopolyploids. First, we describe
      an amplified fragment length polymorphism (AFLP)--complementary DNA (cDNA)
      display method that allows the discrimination of homoeologous loci based on
      restriction polymorphisms between the progenitors. Second, we describe microarray
      analyses that can be used to compare gene expression differences between the
      allopolyploids and respective progenitors using appropriate experimental design
      and statistical analysis. We demonstrate the utility of these two complementary
      methods and discuss the pros and cons of using the methods to analyze gene
      expression changes in autopolyploids and allopolyploids. Furthermore, we describe
      these methods in general terms to be of wider applicability for comparative gene
      expression in a variety of evolutionary, genetic, biological, and physiological
      contexts.

PMID- 15865986
TI  - Designing experiments using spotted microarrays to detect gene regulation
      differences within and among species.
AB  - Comparative studies of genome-wide gene expression must account for variation not
      only among species, but also within species. Such studies are necessarily large
      in scale, because they incorporate experiments on multiple individuals of
      multiple species in multiple developmental stages in multiple environmental
      conditions. If the experiments are carefully designed and performed, the data
      they provide are worth the effort. We describe the utility of spotted microarrays
      for these studies and highlight experimental design criteria that will maximize
      inferential and statistical power. We conclude with a discussion of experimental
      protocols that are designed for investigations of differential gene expression
      and their pitfalls.

PMID- 15865987
TI  - Methods for studying the evolution of plant reproductive structures: comparative
      gene expression techniques.
AB  - A major component of evolutionary developmental (evo-devo) genetics is the
      analysis of gene expression patterns in nonmodel species. This comparative
      approach can take many forms, including reverse-transcriptase polymerase chain
      reaction, Northern blot hybridization, and in situ hybridization. The choice of
      technique depends on several issues such as the availability of fresh tissue, as
      well as the expected expression level and pattern of the candidate gene in
      question. Although the protocols for these procedures are fairly standard,
      optimization is often required because of the specific characteristics of the
      species under analysis. This chapter describes several methods commonly used to
      determine gene expression patterns in angiosperms, particularly in floral
      tissues. Suggestions for adapting basic protocols for diverse taxa and
      troubleshooting are also extensively discussed.

PMID- 15865988
TI  - Developing antibodies to synthetic peptides based on comparative DNA sequencing
      of multigene families.
AB  - Using antisera to analyze the expression of specific gene products is a common
      procedure. However, in multigene families, such as the beta-keratins of the avian
      integument where strong homology exists among the scale (ScbetaK), claw
      (ClbetaK), feather (FbetaK), and feather-like (FlbetaK) subfamilies, determining
      the cellular and tissue expression patterns of the subfamilies is difficult
      because polyclonal antisera produced from any one protein recognize all family
      members. Traditionally, researchers produced and screened multiple monoclonal
      antisera produced from the proteins of interest until an antiserum with
      sufficient specificity could be obtained. Unfortunately, this approach requires a
      lot of effort, and once obtained, such antisera may have limited applications.
      Here, we present procedures by which comparative DNA sequences of members from
      the beta-keratin multigene family were translated and aligned to identify amino
      acid domains that were conserved within the FbetaK subfamily, but which were
      divergent from the other subfamilies. A synthetic 23-mer peptide with the
      conserved amino acid sequence was generated and used to produce a polyclonal
      antiserum that recognizes only the FbetaK subfamily of proteins. Western blot
      analysis and confocal microscopy with this antiserum are now providing valuable
      new insights concerning the developmental and evolutionary relationships between
      the scale, claw, and feather proteins found in birds. This represents a powerful
      new approach combining techniques from molecular evolution and developmental
      biology to study the expression and evolution of specific members of multigene
      families.

PMID- 15865989
TI  - Applications of ancestral protein reconstruction in understanding protein
      function: GFP-like proteins.
AB  - Recreating ancestral proteins in the laboratory increasingly is being used to
      study the evolutionary history of protein function. More efficient gene synthesis
      techniques and the decreasing costs of commercial oligosynthesis are making this
      approach both simpler and less expensive to perform. Developments in ancestral
      reconstruction methods, particularly more realistic likelihood models of
      molecular evolution, allow for the accurate reconstruction of more ancient
      proteins than previously possible. This chapter reviews phylogenetic methods of
      ancestral inference, strategies for investigating alternative reconstructions,
      gene synthesis, and design, and an application of these methods to the
      reconstruction of an ancestor in the green fluorescent protein family.

PMID- 15865990
TI  - Advances in phylogeny reconstruction from gene order and content data.
AB  - Genomes can be viewed in terms of their gene content and the order in which the
      genes appear along each chromosome. Evolutionary events that affect the gene
      order or content are "rare genomic events" (rarer than events that affect the
      composition of the nucleotide sequences) and have been advocated by systematists
      for inferring deep evolutionary histories. This chapter surveys recent
      developments in the reconstruction of phylogenies from gene order and content,
      focusing on their performance under various stochastic models of evolution.
      Because such methods are quite restricted in the type of data they can analyze,
      we also present research aimed at handling the full range of whole-genome data.

PMID- 15865991
TI  - Analytical methods for detecting paralogy in molecular datasets.
AB  - Paralogy (common ancestry through gene duplication rather than speciation) is
      widely recognized as an important problem for molecular systematists. This
      chapter introduces the concepts of paralogy and orthology and explains why
      paralogy can complicate both systematic work and other studies of molecular
      evolution. The definition of paralogy is explicitly phylogenetic, and
      phylogenetic methods are crucial in elucidating the pattern of paralogy. In
      particular, knowledge of the species phylogeny is key. I introduce the theory
      behind methods for detecting paralogy and briefly discuss two particular software
      implementations of phylogenetic methods to detect paralogy from molecular data. I
      also introduce a statistical method for detecting paralogy and some future
      directions for work on paralogy detection.

PMID- 15865992
TI  - Analytical methods for studying the evolution of paralogs using duplicate gene
      datasets.
AB  - Gene duplication is widely viewed as an important source of raw material for
      functional innovation in proteins because at least some duplicate copies will
      evolve new or slightly modified functions. The study of the molecular processes
      by which functional innovation occurs interests both evolutionary biologists and
      protein chemists, and the development of methods to investigate these processes
      has led to a productive meeting of disciplines and an availability of
      complementary approaches for exploring datasets. This has resulted in insights
      into past events, prediction of current function, and prediction of future
      change. The methods fall broadly into two categories: those that rely on
      detection of shifts in selective constraints and those that rely on detection of
      correlations between molecular changes and functional shifts. Strengths and
      limitations of the methods are evaluated here in the context of the question
      being addressed, the input required, and the specific metric that is evaluated in
      each test.

PMID- 15865993
TI  - Supertree construction in the genomic age.
AB  - Supertree construction is the process whereby overlapping phylogenetic trees, and
      not character data, are combined to yield a larger, more comprehensive phylogeny.
      In this chapter, I review the logic and methodology behind supertree construction
      and argue that it holds a necessary place in phylogenetic inference. Much of the
      justification for supertrees is admittedly practical. As I show with an empirical
      example, most large groups have insufficient sequence data to build complete
      phylogenies for them. By being able to indirectly combine diverse forms of
      phylogenetic information, supertrees are the best method for constructing
      complete phylogenies of groups with hundreds of species. However, supertree
      construction can also be justified on theoretical grounds. As whole genomic data
      are obtained for increasing numbers of species, the theoretical and practical
      advantages of supertrees together will ensure that the method will play a
      necessary analytical role as part of a divide-and-conquer strategy to
      reconstructing the Tree of Life.

PMID- 15865994
TI  - Maximum-likelihood methods for phylogeny estimation.
AB  - Maximum-likelihood (ML) estimation of phylogenies has reached a rather high level
      of sophistication because of algorithmic advances, improvements in models of
      sequence evolution, and improvements in statistical approaches and application of
      cluster computing. Here, I provide a brief basic background in application of the
      general principle of ML estimation to phylogenetics and provide an example of
      selecting among a nested set of ML models using a dynamic approach to
      hierarchical likelihood-ratio tests. I focus attention on PAUP* because it
      provides unique ease of switching among alternative optimality criteria (e.g.,
      minimum evolution, parsimony, and ML). Further, examples of parametric bootstrap
      tests are provided that demonstrate statistical tests of phylogenetic hypotheses
      and model adequacy, in an absolute rather than relative sense. The increasing
      availability of clustered, parallelized computation makes use of such parametric
      approaches feasible.

PMID- 15865995
TI  - Context dependence and coevolution among amino acid residues in proteins.
AB  - As complete genomes accumulate and the generation of genomic biodiversity
      proceeds at an accelerating pace, the need to understand the interaction between
      sequence evolution and protein structure and function rises in prominence. The
      pattern and pace of substitutions in proteins can provide important clues to
      functional importance, functional divergence, and adaptive response. Coevolution
      between amino acid residues and the context dependence of the evolutionary
      process are often ignored, however, because of their complexity, but they are
      critical for the accurate interpretation of reconstructed evolutionary events.
      Because residues interact with one another, and because the effect of
      substitutions can depend on the structural and physiological environment in which
      they occur, an accurate science of evolutionary functional genomics and a
      complete understanding of selection in proteins require a better understanding of
      how context dependence affects protein evolution. Here, we present new evidence
      from vertebrate cytochrome oxidase sequences that pairwise coevolutionary
      interactions between protein residues are highly dependent on tertiary and
      secondary structure. We also discuss theoretical predictions that impinge on our
      expectations of how protein residues may interact over long distances because of
      their shared need to maintain protein stability.

PMID- 15865996
TI  - Intein-mediated protein trans-splicing and transgene containment in plastids.
AB  - Transgenes in plastids are contained by stringent maternal inheritance in most
      cultivated plant species and their expression yields high levels of protein with
      bona fide structure. Nevertheless, transfer of plastid genes to the nucleus has
      been reported, with implications for transgene containment. The significance of
      these transfers will depend on the likelihood that they will become functional
      nuclear genes. Recently a novel approach, intein-mediated protein trans-splicing,
      has been demonstrated promising to yield transgenic plants with greatly reduced
      risk of genetic outcrossing.

PMID- 15865997
TI  - Single base hits score a home run in wheat.
AB  - Finding a way to identify point mutants for a genome in which there are six
      copies of every gene seems a daunting task, however this has recently been
      reported. In this research, the redundancy in the wheat genome proved a help
      instead of a hindrance and the results suggest a promising approach in functional
      genomics of polyploid crop species. It is now feasible to generate point
      mutations in all the homologs for a particular gene directly in a polypoid
      commercial crop variety and then combine them, thus avoiding undesirable, linked
      traits that often complicate introgressing traits into crops from wild relatives.

PMID- 15865998
TI  - Genetically modified organisms and the EU.

PMID- 15865999
TI  - Quenched probes for highly specific detection of cellular RNAs.
AB  - Nucleic acid-based RNA detection is a promising field in molecular biotechnology
      that is leading to the rapid and accurate identification of microorganisms,
      diagnosis of infections and imaging of gene expression. The specificity of short
      synthetic DNA probes raises the hope of distinguishing small differences in
      sequence, ultimately achieving single nucleotide resolution. Recent work using
      quenched fluorescently labeled oligonucleotide probes as sensors for RNA in
      bacterial and human cells has overcome several difficult hurdles on the way to
      these goals, including delivery of probes to live cells, accessing RNA sites
      containing a high degree of secondary structure, and eliminating many sources of
      background. Two new classes of quenched oligonucleotide probes, molecular beacons
      and quenched auto-ligation probes, have shown the most promise for in situ RNA
      detection. High-specificity detection, at the single-nucleotide resolution level,
      is now possible in solution with these classes of probes. However, for
      applications in intact cells, signal and background issues still need to be
      addressed before the full potential of these methods is achieved.

PMID- 15866000
TI  - Improving enzyme properties: when are closer mutations better?
AB  - Study of mutations that improve enzyme properties reveals that in many, but not
      all, cases closer mutations are more effective than distant ones. For
      enantioselectivity, substrate selectivity and new catalytic activity (catalytic
      promiscuity) closer mutations improved enzymes more effectively than distant
      ones. However, both close and distant mutations can improve activity, thermal
      stability and also probably stability toward organic solvents. Typical random
      mutagenesis methods, such as error-prone PCR, create greater numbers of distant
      mutations than close mutations because enzymes contain more amino acids distant
      from the active site than close to the active site. This suggests that instead of
      mutating the entire enzyme, focusing mutations near the substrate-binding site
      might dramatically increase the success rate in many directed evolution
      experiments.

PMID- 15866001
TI  - Breakthrough in chloroplast genetic engineering of agronomically important crops.
AB  - Chloroplast genetic engineering offers several unique advantages, including high
      level transgene expression, multi-gene engineering in a single transformation
      event and transgene containment by maternal inheritance, as well as a lack of
      gene silencing, position and pleiotropic effects and undesirable foreign DNA.
      More than 40 transgenes have been stably integrated and expressed using the
      tobacco chloroplast genome to confer desired agronomic traits or express high
      levels of vaccine antigens and biopharmaceuticals. Despite such significant
      progress, this technology has not been extended to major crops. However, highly
      efficient soybean, carrot and cotton plastid transformation has recently been
      accomplished through somatic embryogenesis using species-specific chloroplast
      vectors. This review focuses on recent exciting developments in this field and
      offers directions for further research and development.

PMID- 15866002
TI  - How prenatal diagnosis became acceptable in France.
AB  - Since the 1960s, prenatal diagnosis techniques have been developed in
      industrialized countries. There is no therapeutic treatment for most of the
      diagnosed foetuses and the only solution medicine can offer is abortion;
      therefore, the techniques might seem controversial. Here, I aim to explore why
      some prenatal diagnosis and screening techniques are widely used when pregnant
      women are often ambivalent about them. This article draws on previous
      sociological work, accounts of health practitioners and a case study of the
      diffusion of Down's Syndrome prenatal diagnosis in France. It argues that
      numerous factors, other than the demand of the users, can contribute to speed up
      the diffusion of a technique.

PMID- 15866003
TI  - Sensing the sea.
AB  - The development of the 'ecosystem approach' to the management of marine systems
      is leading to a requirement for data to be collected with greater frequency and
      spatial resolution than has been necessary in the past. This is being met both by
      the analysis of more samples (to better describe variability and temporal change)
      and by the deployment of instrumented platforms that gather data over long time
      periods. To meet these requirements in the hostile conditions at sea, a range of
      sensors based on physical, chemical and biological responses is being developed.
      These sensors have applications in laboratory analysis of collected samples,
      during field studies and directly in situ at remote sites for real-time
      observations of environmental trends. Here, we consider the role that biosensors
      could have in future marine monitoring programmes.

PMID- 15866004
TI  - Photosynthetic proteins for technological applications.
AB  - Photosynthetic proteins are a source of biological material well-suited to
      technological applications. They exhibit light-induced electron transfer across
      lipid membranes that can be exploited for the construction of photo-optical
      electrical devices. The structure and function of photosynthetic proteins differ
      across the photosynthetic evolutionary scale, allowing for their application in a
      range of technologies. Here we provide a general description of the basic and
      technical research in this sector and an overview of biochips and biosensors
      based on photochemical activity that have been developed for the bioassay of
      pollutants.

PMID- 15866005
TI  - Transforming kelp into a marine bioreactor.
AB  - The past decade has seen the genetic engineering of various types of seaweed. To
      date, genetic transformation studies have been carried out in several seaweeds,
      including the red seaweeds Porphyra, Gracilaria, Grateloupia, Kappaphycus and
      Ceramium and the green seaweed Ulva. A genetic transformation model system has
      been established in the most commonly cultivated seaweed, the brown seaweed
      Laminaria japonica (kelp), based on the transfer of technology used in land plant
      transformation and also by modulating the seaweed life cycle. This model showed
      the potential for application of transgenic kelp to the production of valuable
      products and an indoor cultivation system for transgenic kelp was proposed,
      taking into account necessary factors for bio-safety. In this review, the
      establishment at use of the kelp transformation model is introduced, highlighting
      the potential for transforming kelp into a marine bioreactor.

PMID- 15866006
TI  - Adverse impact of surgical site infections in English hospitals.
AB  - Between October 1997 and June 2001, 140 English hospitals participating in the
      surveillance of surgical site infection (SSI) with the Nosocomial Infection
      National Surveillance Service (NINSS) reported 2832 SSIs following 67 410
      surgical procedures in nine defined categories of surgery. Limb amputation had
      the highest incidence of SSI with 14.3 SSIs per 100 operations. For all
      categories of surgery, except knee prosthesis (P=0.128), there was a linear
      increase in the incidence of SSI when the American National Nosocomial Infections
      Surveillance risk index increased. Superficial incisional SSI was more common
      than deep incisional and organ/space SSI, and accounted for more than half of all
      SSIs for all categories of surgery. The postoperative length of stay (LOS) was
      longer for patients with SSI, and when adjusted for other factors influencing
      LOS, the extra LOS due to SSI ranged from 3.3 days for abdominal hysterectomy to
      21.0 days for limb amputation, and was at least nine days for the other
      categories. The additional cost attributable to SSI ranged from pound959 for
      abdominal hysterectomy to pound6103 for limb amputation. Deep incisional and
      organ/space SSI combined incurred a greater extra LOS and cost than superficial
      incisional SSI for all categories of surgery, except limb amputation. The crude
      mortality rate was higher for patients with SSI for all categories of surgery
      but, after controlling for confounding, only patients with SSI following hip
      prosthesis had a mortality rate that was significantly higher than those without
      SSI [odds ratio (OR)=1.8, P=0.002]. However, the adjusted mortality rate for
      patients with deep incisional and organ/space SSI compared with those without SSI
      was significantly higher for vascular surgery (OR=6.8, P<0.001), hip prosthesis
      (OR=2.5, P=0.005) and large bowel surgery (OR=1.8, P=0.04). This study shows that
      the adverse impact of SSI differs greatly for different categories of surgery,
      and highlights the importance of measuring the impact for defined categories
      rather than for all SSIs and all surgical procedures.

PMID- 15866008
TI  - Impact of local guidelines and an integrated dispensing system on antibiotic
      prophylaxis quality in a surgical centre.
AB  - Surgical antibiotic prophylaxis is effective in preventing postoperative wound
      infections. Guidelines are designed to optimize antimicrobial use in this
      setting. The aim of this study was to assess antibiotic use in surgical
      prophylaxis in a surgical hospital before and after the implementation of both
      local antibiotic prophylaxis guidelines and a specific medication set for various
      surgical procedures. The appropriateness of surgical antibiotic prophylaxis
      increased from 50.9% in the pre-implementation stage to 94.9% in the
      postimplementation stage (P<0.001). The implementation of a multidisciplinary
      protocol and design of medication sets helped to improve the practice of surgical
      antibiotic prophylaxis.

PMID- 15866007
TI  - Significant reduction of endemic MRSA acquisition and infection in cardiothoracic
      patients by means of an enhanced targeted infection control programme.
AB  - Due to increasing methicillin-resistant Staphylococcus aureus (MRSA) infection in
      cardiothoracic patients at St Thomas' Hospital, an enhanced infection control
      programme was introduced in September 2000. It was based on UK national
      guidelines on the control of MRSA and targeted additional identified risk factors
      for surgical site infection (SSI). It included recognition of the problem by
      senior staff and their taking responsibility for it; intensive support, education
      and advice from the infection control team; improved ward and theatre hygiene;
      pre-admission, admission and weekly MRSA screening; isolation and clearance
      treatment; nursing care pathways for MRSA colonized patients; and teicoplanin
      plus gentamicin surgical prophylaxis. The effectiveness of the programme was
      assessed by retrospective analysis of computerized patient data for the 16 months
      before and after the introduction of the programme. There was no significant
      change in the number of operations or the proportion of patients admitted with
      MRSA, although nine patients were cleared of carriage before admission. However,
      there were significant falls in the proportion of patients acquiring MRSA on the
      ward [38/1036 to 14/921, P=0.003, RR 2.4 (95%CI 1.32-4.42)] and in the rate of
      bloodstream MRSA infections [12/1075 to 2/956, P=0.014, RR 5.34 (95%CI 1.20
      23.78)]. Sternal and leg wound infections both halved (from 28/1075 to 13/956 and
      16/1075 to 7/956, respectively) but this did not reach statistical significance.
      These results demonstrate that an enhanced, targeted infection control programme
      based on the UK national guidelines, SSI prevention guidelines and local risk
      assessment can reduce the incidence of nosocomial MRSA acquisition and invasive
      infection in cardiothoracic patients in the face of continuing endemic risk.

PMID- 15866009
TI  - Comparison of contamination rates of catheter-drawn and peripheral blood
      cultures.
AB  - The aim of this study was to assess the sensitivity and specificity of catheter
      drawn and peripheral blood cultures. Paired blood culture samples collected over
      a 44-month period from a 280 bed Brisbane metropolitan hospital were analysed,
      using standard clinical and microbiological criteria, to determine whether blood
      culture isolates represented true bacteraemias or contamination. Catheter
      collected cultures had a specificity of 85% compared with 97% for peripheral
      cultures. In only two instances (0.2%) was the diagnosis of clinically
      significant bacteraemia made on the basis of catheter culture alone. This study
      concluded that catheter-collected samples are not a good test for true
      bacteraemia, and that peripheral cultures are more reliable when the results of
      the paired cultures are discordant.

PMID- 15866010
TI  - Unexpected hospital-acquired bacteraemia in patients at low risk of bloodstream
      infection: the role of a heparin drip.
AB  - Following a cluster of cases of unexpected hospital-acquired bacteraemia
      suspected to be related to an intravenous (iv) heparin drip, all cases of
      hospital-acquired primary bloodstream infection (BSI) in patients at low risk of
      bacteraemia were analysed over a four-year period. Ninety-six bacteraemic
      patients (6%) from 1618 episodes of hospital-acquired bacteraemia had a
      peripheral iv line as the only risk factor. These patients were divided into two
      groups: 60 patients with phlebitis and 36 without local signs of inflammation.
      Baseline features of the two groups were comparable, but in univariate and
      multivariate analysis, a significant association was found between iv heparin
      use, predominance of Gram-negative organisms (especially Klebsiella, Serratia and
      Enterobacter species), and absence of phlebitis. In spite of clear statistical
      association, however, the means by which the heparin solution became contaminated
      with Gram-negative organisms remained unknown. Following implementation of
      infection control methods concerning heparin handling, no more cases occurred.
      Unexpected hospital-acquired Gram-negative bacteraemia in patients with
      peripheral iv lines should prompt investigation of potential infusate-related
      infection, especially in patients without phlebitis and those receiving iv
      heparin.

PMID- 15866011
TI  - A comparative study of risk factors and outcome among outpatient-acquired and
      nosocomial candidaemia.
AB  - Candidaemia is perceived as a nosocomial infection. The aim of this study was to
      describe all cases of candidaemia that occurred in the outpatient setting, and to
      compare risk factors and outcome among patients with outpatient-acquired and
      nosocomial candidaemia. During 1995 and 2003, 210 patients developed candidaemia
      at our institution, and 9.0% were outpatient acquired. Major underlying diseases
      were cancer (47.4%) and chronic renal failure (36.8%). Most occurred within 24 h
      of hospitalization (63.2%), and 83.7% were caused by species other than Candida
      albicans, mainly Candida parapsilosis (36.8%). Candida spp. were isolated from
      catheters in 21% of cases, and 52.6% of patients had been admitted to hospital in
      the 60 days preceding candidaemia. Compared with patients with nosocomial
      candidaemia, chronic renal failure was more frequent in the outpatient group, who
      were also more commonly exposed to haemodialysis. Ileus, gastrointestinal
      bleeding, previous bacteraemia, use of proton pump inhibitors, previous stay in
      the intensive care unit and requirement for antibiotics, blood transfusion,
      vasopressors and invasive medical procedures were more frequent in the nosocomial
      group. Overall mortality was high in both groups. Candidaemia must be considered
      as a potential cause of sepsis in the community, and it is associated with a high
      mortality rate.

PMID- 15866012
TI  - Institutional risk factors for outbreaks of nosocomial gastroenteritis: survival
      analysis of a cohort of hospital units in South-west England, 2002-2003.
AB  - Nosocomial outbreaks of gastroenteritis are a major burden on hospital inpatient
      services, costing an estimated pound115 million annually to the English National
      Health Service. We actively followed-up 171 inpatient units from four major acute
      hospitals and 11 community hospitals in South-west England for one year.
      Outbreaks of gastroenteritis were ascertained through an active surveillance
      network using standard clinical definitions. Survival analysis Cox regression
      models using an outbreak of gastroenteritis as the endpoint were fitted to
      identify institutional and operational attributes related to increased outbreak
      rates at the level of the care unit. Greater number of beds in unit [hazard ratio
      (HR) 1.22 (per 10 additional beds), 95% confidence intervals (CI) 0.96-1.55] was
      associated with increased hazard, as were geriatric (HR 2.6, 95%CI 1.6-4.3) and
      general medical (HR 1.7, 95%CI 1.1-2.6) care units. The average length of stay on
      a unit was inversely associated with outbreak incidence [HR=0.89 (per additional
      week of stay), 95%CI 0.80-0.99]. Larger care units and those with higher
      throughput have increased rates of gastroenteritis outbreaks. These results
      should guide infection control policy and support the design of hospitals with
      smaller care units.

PMID- 15866013
TI  - Efficacy of three ethanol-based hand rubs against feline calicivirus, a surrogate
      virus for norovirus.
AB  - We investigated the efficacy of three ethanol-based hand rubs (Sterillium
      Virugard, 95% ethanol; Sterillium Rub, 80% ethanol; Desderman N, 75.1% ethanol)
      against feline calicivirus (FCV), the surrogate virus for norovirus, on
      artificially contaminated hands of healthy volunteers. The ASTM E 1838-02
      standard was used. Experiments were controlled with 70% ethanol and 70% propan-1
      ol which were previously found to have maximal efficacy against FCV. In the first
      step, three different organic loads (5% fetal bovine serum, 5% faecal suspension
      and the tripartite ASTM load) were compared. A significant influence of the type
      of organic load was found (P<0.001, ANOVA). In the second step, the hand rubs
      were investigated with a 5% faecal suspension as a challenging organic load. The
      hand rub based on 95% ethanol was more effective than those based on 70% ethanol
      (mean log10 reduction factor: 2.17 vs. 1.56; P=0.17) and 70% propan-1-ol (mean
      RF: 1.63 vs. 0.95; P=0.0003). The hand rub based on 80% ethanol was also more
      effective than those based on 70% ethanol (mean RF: 1.25 vs. 1.03: P=0.20) and
      70% propan-1-ol (mean RF: 1.43 vs. 1.09; P=0.03). The hand rub based on 75.1%
      ethanol was less effective than those based on 70% ethanol (mean RF: 1.07 vs.
      1.27; P=0.47) and 70% propan-1-ol (mean RF: 0.78 vs. 0.97; P=0.35). Based on our
      data, ethanol has superior efficacy against FCV than propan-1-ol. In addition, a
      higher ethanol concentration in three commercially available hand rubs was
      associated with better efficacy against FCV.

PMID- 15866014
TI  - Evaluation of the effectiveness of the Pastormaster method for disinfection of
      legionella in a hospital water distribution system.
AB  - The Pastormaster method consists of heating the water of hospital distribution
      systems at a specific point to a sufficient temperature for a minimum amount of
      time to eradicate legionella. The object of this study was to evaluate the
      effectiveness of the Pastormaster method for legionella disinfection in a
      hospital environment. A two-phase procedure was performed: hydraulic optimization
      of the water supply circuit, and implementation of the Pastormaster method. Water
      samples were taken at 10 representative points in the hospital hot-water system
      and cultured microbiologically. Other physical and chemical measurements were
      also determined. Implementation of the Pastormaster method and correction of the
      deficiencies identified during a hydraulic system audit confirmed the absence of
      legionella in the hospital water distribution system. The combination of
      implementation of the Pastormaster method and conduction of a hydraulic audit
      designed to identify and remedy any possible problems in water circulation is
      effective in minimizing the risk of legionella contamination in hospital water
      distribution systems.

PMID- 15866015
TI  - Use of terminal tap water filter systems for prevention of nosocomial
      legionellosis.
AB  - Hospital water supplies often contain Legionella spp. and represent a potential
      source of nosocomial infection, especially for immunocompromised patients or
      those in intensive care units. Therefore, pathogen-free water should be provided
      for such high-risk patients. Surveillance of splash water was performed in high
      risk patient care areas at Berlin Charite-University Medicine (506 samples) and
      Medical School Hannover (767 samples) to investigate the ability to provide water
      that was free from Legionella spp. by the use of disposable, terminal tap water
      filter systems with non-impregnated, as well as impregnated, filters with
      prolonged usage intervals. Twenty (Berlin) and 32 (Hannover) water outlets were
      provided with disposable filters with a pore size of 0.2 microm. Testing of
      unfiltered tap water revealed growth of Legionella spp. in 53 of 210 (Berlin) and
      30 of 32 (Hannover) samples. Non-impregnated, terminal, disposable water filters
      at taps used for high-risk patient care led to water free from Legionella spp. in
      154 of 155 (99.4%) samples after three to four days and in 137 of 141 (97.2%)
      samples after six to seven days. When testing a new impregnated filter, 255 of
      256 (99.6%) samples remained free from Legionella spp. after continuous use for
      seven days, as recommended by the manufacturers, and also after 10 days. Samples
      that were positive for Legionella spp. contained 1-4 cfu/mL. We believe that an
      impregnated filter system is suitable for the prevention of nosocomial
      Legionellosis in high-risk patient care areas.

PMID- 15866016
TI  - Knowledge and opinions of surgical patients regarding nosocomial infections.
AB  - Sixty-five inpatients in various surgery departments were questioned about their
      knowledge and opinions regarding nosocomial infection, the information they were
      given on nosocomial infection, and their supposed attitude should they contract a
      nosocomial infection. RESULTS: Seventeen (26%, [16-39%]) were able to describe
      nosocomial infections as infections acquired in hospital. Identification of
      nosocomial infections as hospital-acquired infections was significantly
      associated with a high educational level and with having a member of their own
      family working in a health-related field. Fifty-two patients (80.0%, [68.2
      88.9%]) stated that during their hospitalization they had received no information
      concerning nosocomial infections and 50 patients (76.9% [64.8-86.5]) mentioned
      that patients would welcome information about nosocomial infections. Thirty-three
      patients [50.8, 95% CI(38.6-62.9%)] declared that they would seek legal action
      against the hospital should they contract a nosocomial infection. There was a
      trend toward a higher probability of legal action in patients who rated their own
      risk of nosocomial infection as low or absent versus those who rated their own
      risk of nosocomial infection as medium or high (58.0% vs. 28.6%, p=0.051). The
      intention of seeking legal action against the hospital in case of nosocomial
      infection was not significantly influenced by patients' opinion regarding
      nosocomial infection preventability.

PMID- 15866017
TI  - National hospital infection surveillance on methicillin-resistant Staphylococcus
      aureus.
AB  - Surveillance of methicillin-resistant Staphylococcus aureus (MRSA) infections in
      Japan was performed in 1995 and 1996. Hospital infection rates of MRSA appear to
      have remained stable in recent years, and this study was undertaken to test this
      hypothesis. In national surveillance, the incidence of MRSA hospital infections
      per 100 admissions remained stable at between 0.7 and 0.8 from 1999 to 2003, with
      a tendency towards a slight decline. This study shows that precautions against
      MRSA infection in Japan may prove to be an effective preventive measure.

PMID- 15866018
TI  - Mortality rate, length of stay and extra cost of sternal surgical site infections
      following coronary artery bypass grafting in a private medical centre in Turkey.
AB  - Florence Nightingale Hospital is a 300-bed, university-affiliated, private
      medical centre with a large open heart surgery programme in Istanbul, Turkey. In
      this study, the mortality rates, lengths of stay (LOS) and extra costs of
      patients with deep sternal surgical site infections (DSSSIs) and superficial
      sternal surgical site infections (SSSSIs) following coronary artery bypass
      grafting (CABG) were determined from January 1999 to December 2002. Group I
      included 52 patients with DSSSIs, Group II included 36 patients with SSSSIs and
      Group III included 88 controls. The controls were selected at random from
      patients operated within the same year, with the same sex and age within five
      years, but who had not developed infection. Mortality rates in Groups I, II and
      III were 19.2%, 0% and 4.5%, respectively; the mortality rate in Group I was
      significantly different from that in Groups II and III (P<0.005). LOS was 47, 33
      and 12 days for Groups I, II and III, respectively, and LOS was statistically
      different for each group (P<0.005). The costs of extra LOS, antibiotics, and
      radiological, microbiologial and other laboratory examinations for Groups I and
      II were US$6850.93 and US$3740.58, respectively. Both DSSSI and SSSSI following
      CABG extended the LOS and increased the cost, and DSSSI was significantly
      associated with a high mortality rate. These results suggest the need for
      improved infection control measures to reduce SSSIs following CABG. As an
      important component of the extra cost is the extra LOS, it is essential to
      shorten this period. This may be particularly applicable in patients with SSSSIs.

PMID- 15866019
TI  - Efficacy of 10 different cleaning processes in a washer-disinfector for flexible
      endoscopes.

PMID- 15866021
TI  - Nosocomial cross-infection of a child with cystic fibrosis with Haemophilus
      influenzae serotype e.

PMID- 15866022
TI  - MRSA carriage in a pet therapy dog.

PMID- 15866023
TI  - First report of catalase-negative methicillin-resistant Staphylococcus aureus
      sepsis.

PMID- 15866025
TI  - Bub1 and the multilayered inhibition of Cdc20-APC/C in mitosis.
AB  - To ensure the accuracy of chromosome segregation in mitosis, the spindle
      checkpoint blocks the activity of the anaphase-promoting complex APC/C until all
      chromosomes are properly bi-orientated on the metaphase spindle. How the
      checkpoint machinery actually inhibits the APC/C is still unclear. A new paper by
      Tang and coworkers helps further our understanding of this complex and
      fundamental process.

PMID- 15866026
TI  - Decisions, decisions: beta-catenin chooses between adhesion and transcription.
AB  - beta-catenin functions in both cell adhesion and transcription. Properly choosing
      between these functions is crucial for normal development, and the wrong choice
      can lead to cancer. Recent studies have revealed molecular switches that help
      dictate whether beta-catenin interacts with adhesive or transcriptional
      complexes. Cara Gottardi and Barry Gumbiner identify Wnt-induced beta-catenin
      conformational changes that favor assembly into transcription complexes, whereas
      alpha-catenin-associated beta-catenin appears to favor adhesion. Furthermore,
      Felix Brembeck and colleagues reveal that phosphorylation dissociates beta
      catenin from adhesion complexes while enhancing BCL9-2 binding to promote
      transcription.

PMID- 15866027
TI  - E-cadherin-mediated adhesion is not the founding event of epithelial cell
      polarity in Drosophila.
AB  - Formation of a polarized epithelial layer is a fundamental step during the
      development of multicellular animals. This process involves the coordinated
      action of adhesion molecules, actin remodeling and spatial organization of
      membrane traffic. A recent article describes a new hierarchy for the development
      of epithelial polarity in the early Drosophila embryo. Bazooka, a Par-3 homolog,
      is properly localized in the absence of adherens junctions, indicating that the
      formation of epithelial junctions is not the founding event of epithelial
      polarization.

PMID- 15866028
TI  - Aurora kinases, aneuploidy and cancer, a coincidence or a real link?
AB  - As Aurora kinases are overexpressed in a large number of cancers, and ectopic
      expression of Aurora generates polyploid cells containing multiple centrosomes,
      it has been tempting to suggest that Aurora overexpression provokes genetic
      instability underlying the tumorigenesis. However, examination of the evidence
      suggests a more complex relationship. Overexpression of Aurora-A readily
      transforms rat-1 and NIH3T3 cells, but not primary cells, whereas overexpression
      of Aurora-B induces metastasis after implantation of tumors in nude mice. Why do
      polyploid cells containing abnormal centrosome numbers induced by Aurora not get
      eliminated at cell-cycle checkpoints? Does this phenotype determine the origin of
      cancer or does it only promote tumor progression? Would drugs against Aurora
      family members be of any help for cancer treatment? These and related questions
      are addressed in this review (which is part of the Chromosome Segregation and
      Aneuploidy series).

PMID- 15866029
TI  - RNA silencing and genome regulation.
AB  - Closely related RNA silencing phenomena such as posttranscriptional and
      transcriptional gene silencing (PTGS and TGS), quelling and RNA interference
      (RNAi) represent different forms of a conserved ancestral process. The biological
      relevance of these RNA-directed mechanisms of silencing in gene regulation,
      genome defence and chromosomal structure is rapidly being unravelled. Here, we
      review the recent developments in the field of RNA silencing in relation to other
      epigenetic phenomena and discuss the significance of this process and its targets
      in the regulation of modern eukaryotic genomes.

PMID- 15866030
TI  - Probing phosphoinositide functions in signaling and membrane trafficking.
AB  - The inositol phospholipids (PIs) comprise a family of eight species with
      different combinations of phosphate groups arranged around the inositol ring. PIs
      are among the most versatile signaling molecules known, with key roles in
      receptor-mediated signal transduction, actin remodeling and membrane trafficking.
      Recent studies have identified effector proteins and specific lipid-binding
      domains through which PIs signal. These lipid-binding domains can be used as
      probes to further our understanding of the spatial and temporal control of
      individual PI species. New layers of complexity revealed by the use of such
      probes include the occurrence of PIs at intracellular locations, the
      identification of phosphatidylinositol signaling hotspots and the presence of non
      membrane pools of PIs in cell nuclei.

PMID- 15866031
TI  - The Trojan horse: survival tactics of pathogenic mycobacteria in macrophages.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis, has infected
      billions of people worldwide. A key to the success of M. tuberculosis and related
      pathogenic mycobacteria lies in their ability to persist within the hostile
      environment of the host macrophage. After internalization by macrophages, most
      microbes are rapidly transported to lysosomes in which they are destroyed. By
      contrast, pathogenic mycobacteria prevent fusion of phagosomes with lysosomes,
      thereby surviving intracellularly. Recent progress in understanding the molecular
      biology of host-mycobacteria interactions is providing insights into these
      survival tactics.

PMID- 15866032
TI  - Plant cytokinesis: fission by fusion.
AB  - Cytokinesis partitions the cytoplasm of a dividing cell. Unlike yeast and animal
      cells, which form cleavage furrows from the plasma membrane, cells in higher
      plants make a new membrane independently of the plasma membrane by homotypic
      fusion of vesicles. In somatic cells, a plant-specific cytoskeletal array, called
      a phragmoplast, is thought to deliver vesicles to the plane of division. Vesicle
      fusion generates a membranous network, the cell plate, which, by fusion of later
      arriving vesicles with its margin, expands towards the cell periphery and
      eventually fuses with the plasma membrane. In this review (part of the
      Cytokinesis series), I describe recent studies addressing the mechanisms that
      underlie cell-plate formation and the coordinated dynamics of membrane fusion and
      cytoskeletal reorganization during progression through cytokinesis.

PMID- 15866033
TI  - Denitrification in pathogenic bacteria: for better or worst?
AB  - A large variety of physiological and taxonomic groups have the ability to use
      nitrogen oxides as alternative electron acceptors. Brucella spp. is an alpha
      proteobacteriaceae that induces a persistent disease in some mammals. Recent work
      has revealed that a denitrifying gene cluster is important in the interaction of
      Brucella neotomoae with its host.

PMID- 15866034
TI  - Archaea with square cells.
AB  - Two groups of microbiologists have independently isolated 'Walsby's square
      bacterium' from salt crystallizer ponds; its growth depends on pyruvate. Genetic
      analysis shows that the squares, discovered 25 years ago on the Sinai Peninsula,
      are archaea rather than bacteria. These transparent tile-like cells might have
      been dismissed as surface artefacts of salt crystals but for their gas vesicles-
      structures peculiar to prokaryotic organisms. Paradoxically, the square archaea
      are the dominant microorganisms in some hypersaline environments and might be
      globally important.

PMID- 15866035
TI  - Insights into the obligate methanotroph Methylococcus capsulatus.
AB  - Completion of the genome sequence of Methylococcus capsulatus Bath is an
      important event in molecular microbiology, and an achievement for which the
      authors deserve congratulation. M. capsulatus, along with other methanotrophs,
      has been the subject of intense biochemical and molecular study because of its
      role in the global carbon cycle: the conversion of biogenic methane to carbon
      dioxide. The methane monooxygenase enzymes that are central to this process also
      have high biotechnological potential. Analysis of the genome sequence will
      potentially accelerate elucidation of the regulation of methane-dependent
      metabolism in obligate methanotrophs, and help explain the cause of obligate
      methanotrophy, the phenomenon making most methanotrophs unable to grow on any
      substrates other than methane and a very small number of other one-carbon
      compounds.

PMID- 15866036
TI  - Trimeric autotransporters: a distinct subfamily of autotransporter proteins.
AB  - Autotransporter proteins are a large family of gram-negative bacterial
      extracellular proteins. These proteins have a characteristic arrangement of
      functional domains, including an N-terminal signal peptide, an internal passenger
      domain, and a C-terminal translocator domain. Recent studies have identified a
      novel subfamily of autotransporters, defined by a short trimeric C-terminal
      translocator domain and known as trimeric autotransporters. In this article, we
      review our current knowledge of the structural and functional characteristics of
      trimeric autotransporters, highlighting the distinctions between this subfamily
      and conventional autotransporters. We speculate that trimeric autotransporters
      evolved to enable high-affinity multivalent adhesive interactions with host
      surfaces and circulating host molecules to take place.

PMID- 15866037
TI  - Mycobacterium tuberculosis as viewed through a computer.
AB  - Mathematical models are emerging as important tools in the study of microbiology.
      As an illustrative example, we present results from several models each generated
      to study the interaction of Mycobacterium tuberculosis and the immune system.
      Different mathematical models were formulated on the basis of assumptions
      regarding system-component interactions, enabling us to explore specific aspects
      at diverse biological scales (e.g. intracellular, cell-cell interactions, and
      cell population dynamics). In addition, we were able to examine both temporal and
      spatial aspects. At each scale, there were consistent themes that emerged as
      determinative in infection outcome. Factors we identified include both host and
      microbial characteristics. The use of the models lies in generating hypotheses
      that can then be tested experimentally. Here, we outline the primary host and
      bacterial factors that we have identified as key mechanisms that contribute to
      the success of M. tuberculosis as a human pathogen. Our goal is to stimulate
      experimentation and foster collaborations between theoretical and experimental
      scientists.

PMID- 15866038
TI  - Geologically ancient DNA: fact or artefact?
AB  - Studies continue to report ancient DNA sequences and viable microbial cells that
      are many millions of years old. In this paper we evaluate some of the most
      extravagant claims of geologically ancient DNA. We conclude that although
      exciting, the reports suffer from inadequate experimental setup and insufficient
      authentication of results. Consequently, it remains doubtful whether amplifiable
      DNA sequences and viable bacteria can survive over geological timescales. To
      enhance the credibility of future studies and assist in discarding false-positive
      results, we propose a rigorous set of authentication criteria for work with
      geologically ancient DNA.

PMID- 15866039
TI  - The choreographed dynamics of bacterial chromosomes.
AB  - Despite decades of study, the exquisite temporal and spatial organization of
      bacterial chromosomes has only recently been appreciated. The direct
      visualization of specific chromosomal loci has revealed that bacteria condense,
      move and position their chromosomes in a reproducible fashion. The realization
      that bacterial chromosomes are actively translocated through the cell suggests
      the existence of specific mechanisms that direct this process. Here, we review
      bacterial chromosome dynamics and our understanding of the mechanisms that direct
      and coordinate them.

PMID- 15866040
TI  - Endolithic fungi in marine ecosystems.
AB  - Fungi are an important constituent of microbial endolithic assemblages in marine
      ecosystems. As euendoliths, they penetrate limestone, mollusk shells and other
      carbonate substrates, where they can exploit mineralized organic matter, attack
      their hosts, or engage in symbiotic relationships. They leave specific boring
      traces, which can be identified in the fossil record and described as trace
      fossils. Their distribution is independent of light and extends from the
      intertidal ranges to abyssal oceanic depths. Important, but insufficiently
      studied, is the role of aggressive endolithic fungi in skeletons of corals where
      they are ubiquitous and globally distributed. In healthy growing reef corals, the
      relationship between the coral coelenterate, endolithic algae and fungi is in a
      state of equilibrium, but can turn detrimental to coral health when reefs are
      exposed to environmental stress.

PMID- 15866041
TI  - ppGpp: a global regulator in Escherichia coli.
AB  - The small nucleotide ppGpp acts as a global regulator of gene expression in
      bacteria. Proteomic analysis of cells lacking ppGpp has shown that this
      nucleotide might affect many more genes than previously anticipated. These
      findings and others suggest that ppGpp causes a redirection of transcription so
      that genes important for starvation survival and virulence are favoured at the
      expense of those required for growth and proliferation. In addition, new insights
      into the mechanism by which ppGpp affects gene expression have been achieved
      owing to in vitro studies of ppGpp function, complemented by structural studies
      of the ppGpp-RNA polymerase complex.

PMID- 15866042
TI  - C-terminal truncation affects kinetic properties of GluR1 receptors.
AB  - GluR1flop receptors in which the C-terminal 52 amino acids had been recombinantly
      removed were characterized with whole-cell recording and binding assays. Compared
      to wildtype GluR1, truncated receptors showed faster desensitization and
      deactivation and they recovered more slowly from desensitization. The EC50 for
      glutamate was increased 2-fold. In binding tests, K(D)s for [3H]fluorowillardiine
      were 1.5 times larger for truncated receptors. According to receptor simulations,
      most differences can be explained if the C-terminal domain is assumed to
      stabilize the ligand-bound closed and open states. The effects on response
      waveforms are different from those caused by phosphorylation, suggesting that the
      C-terminus influences receptor function in multiple ways. Truncated forms of
      GluR1 identical or similar to the one examined here may also be generated by
      calcium-activated proteases during intense synaptic activity. The lowered
      affinity and faster inactivation of these receptors suggests that their presence
      does not represent a risk for neuronal viability.

PMID- 15866043
TI  - Anterograde axonal transport of BDNF and NT-3 by retinal ganglion cells: roles of
      neurotrophin receptors.
AB  - Retinal ganglion cells (RGCs) transport exogenous neurotrophins anterogradely to
      the midbrain tectum/superior colliculus with significant downstream effects. We
      determined contributions of neurotrophin receptors for anterograde transport of
      intraocularly injected radiolabeled neurotrophins. In adult rodents, anterograde
      transport of brain-derived neurotrophic factor (BDNF) was receptor-mediated, and
      transport of exogenous BDNF and neurotrophin-3 (NT-3) was more efficient, per
      RGC, in rodents than chicks. RT-PCR and Western blot analysis of purified murine
      RGCs showed that adult RGCs express the p75 receptor. Anterograde transport of
      BDNF or NT-3 was not diminished in p75 knock-out mice (with unaltered final
      numbers of RGCs), but BDNF transport was substantially reduced by co-injected
      trkB antibodies. In chick embryos, however, p75 antisense or co-injected p75
      antibodies significantly attenuated anterograde transport of NT-3 by RGCs. Thus,
      neither BDNF nor NT-3 utilizes p75 for anterograde transport in adult rodent
      RGCs, while anterograde NT-3 transport requires the p75 receptor in embryonic
      chicken RGCs.

PMID- 15866045
TI  - Semaphorin 3A displays a punctate distribution on the surface of neuronal cells
      and interacts with proteoglycans in the extracellular matrix.
AB  - Secreted semaphorins are essential for neural development and continue to be
      expressed in subpopulations of adult neurons, where they subserve as yet unknown
      functions. We employed functional myc- and GFP-tagged Sema3A proteins to obtain
      insight in the localization of Sema3A in neuronal cells. Sema3A localized to both
      axons and dendrites of cortical neurons. GFP-Sema3A exhibited a characteristic
      punctate distribution on the surface of Neuro-2a cells, localized to migratory
      pathways of cultured cells, and co-localized with and induced clustering of its
      receptor component neuropilin-1. Treatment with excess glycosaminoglycans and
      chondroitinase ABC resulted in the removal of cell surface Sema3A. Heparin
      enhanced Sema3A's binding to neuropilin-1-expressing cells and potentiated its
      growth cone collapsing activity. Together, these results indicate that
      association with proteoglycans in the extracellular matrix of neuronal cells
      plays an important role in the localization of the chemorepulsive guidance cue
      Sema3A, and that this interaction may enhance its biological activity.

PMID- 15866044
TI  - Transgenic inhibition of Nogo-66 receptor function allows axonal sprouting and
      improved locomotion after spinal injury.
AB  - Axon growth after spinal injury is thought to be limited in part by myelin
      derived proteins that act via the Nogo-66 Receptor (NgR). To test this
      hypothesis, we sought to study recovery from spinal cord injury (SCI) after
      inhibiting NgR transgenically with a soluble function-blocking NgR fragment.
      Glial fibrillary acidic protein (gfap) gene regulatory elements were used to
      generate mice that secrete NgR(310)ecto from astrocytes. After mid-thoracic
      dorsal over-hemisection injury, gfap::ngr(310)ecto mice exhibit enhanced
      raphespinal and corticospinal axonal sprouting into the lumbar spinal cord.
      Recovery of locomotion is improved in the gfap::ngr(310)ecto mice. These data
      indicate that the NgR ligands, Nogo-66, MAG, and OMgp, play a role in limiting
      axonal growth in the injured adult CNS and that NgR(310)ecto might provide a
      therapeutic means to promote recovery from SCI.

PMID- 15866046
TI  - SV2A and SV2C contain a unique synaptotagmin-binding site.
AB  - SV2 (Synaptic Vesicle Protein 2) is expressed in neurons and endocrine cells
      where it is required for normal calcium-evoked neurosecretion. In mammals, there
      are three SV2 genes, denoted SV2A, B and C. SV2A interacts with synaptotagmin,
      the prime candidate for the calcium sensor in exocytosis. Here, we report that
      all isoforms of native SV2 bind synaptotagmin and that binding is inhibited by
      calcium, indicating that all isoforms contain a common calcium-inhibited
      synaptotagmin-binding site. The isolated amino termini of SV2A and SV2C supported
      an additional interaction with synaptotagmin, and binding at this site was
      stimulated by calcium. The amino-terminal binding site was mapped to the first 57
      amino acids of SV2A, and removal of this domain decreased calcium-mediated
      inhibition of binding to synaptotagmin, suggesting that it modulates calcium's
      effect on the SV2-synaptotagmin interaction. Introduction of the amino terminus
      of SV2A or SV2C into cultured superior cervical ganglion neurons inhibited
      neurotransmission, whereas the amino terminus of SV2B did not. These observations
      implicate the SV2-synaptotagmin interaction in regulated exocytosis and suggest
      that SV2A and SV2C, via their additional synaptotagmin binding site, function
      differently than SV2B.

PMID- 15866047
TI  - Presenilin endoproteolysis is an intramolecular cleavage.
AB  - Mutations in the presenilin genes (PS) account for most cases of familial
      Alzheimer's disease. PS contain the active site of the gamma-secretase complex
      that cleaves within the transmembrane domain of beta-amyloid precursor protein
      (APP). Full-length PS undergoes regulated endoproteolysis to produce fragments
      that comprise the active form of PS. The "presenilinase" responsible for
      endoproteolysis is unknown but may be the same presenilin-dependent gamma
      secretase activity that cleaves APP. To investigate the mechanism of
      endoproteolysis, we examined sequence specificity at the cleavage site and tested
      whether PS dimers are important for endoproteolysis as well as gamma-secretase
      activity. No single point mutation, or a double mutation M292D/V293K, was able to
      completely abolish endoproteolysis and all mutants supported gamma-secretase
      activity. When wtPS1 was co-expressed with either M292D/V293K or D257A, it was
      unable to restore normal endoproteolysis to either mutant. Lack of transcleavage
      by wtPS1 suggests that PS1 endoproteolysis occurs via intramolecular cleavage and
      does not require dimerization.

PMID- 15866048
TI  - The molluscan RING-finger protein L-TRIM is essential for neuronal outgrowth.
AB  - The tripartite motif proteins TRIM-2 and TRIM-3 have been put forward as putative
      organizers of neuronal outgrowth and structural plasticity. Here, we identified a
      molluscan orthologue of TRIM-2/3, named L-TRIM, which is up-regulated during in
      vitro neurite outgrowth of central neurons. In adult animals, L-Trim mRNA is
      ubiquitously expressed at low levels in the central nervous system and in
      peripheral tissues. Central nervous system expression of L-Trim mRNA is increased
      during postnatal brain development and during in vitro and in vivo neuronal
      regeneration. In vitro double-stranded RNA knock-down of L-Trim mRNA resulted in
      a >70% inhibition of neurite outgrowth. Together, our data establish a crucial
      role for L-TRIM in developmental neurite outgrowth and functional neuronal
      regeneration and indicate that TRIM-2/3 family members may have evolutionary
      conserved functions in neuronal differentiation.

PMID- 15866049
TI  - Two separate metalloproteinase activities are responsible for the shedding and
      processing of the NG2 proteoglycan in vitro.
AB  - A high proportion of NG2 in the adult rat spinal cord is saline-soluble and
      migrates slightly faster than intact NG2 on SDS-PAGE, suggesting that it
      represents the shed ectodomain of NG2. In the injured cerebral cortex, much of
      the overall increase in NG2 is due to the saline-soluble (shed), rather than the
      detergent-soluble (intact), form. Hydroxamic acid metalloproteinase inhibitors,
      but not TIMPs, were able to prevent NG2 shedding in oligodendrocyte precursor
      cells (OPCs) in vitro. The generation of another truncated form of NG2 was,
      however, sensitive to TIMP-2 and TIMP-3. Two observations suggest that NG2 is
      involved in PDGF signaling in OPCs: the rate of NG2 shedding increased with cell
      density and NG2 expression was increased in the absence of PDGF. Ectodomain
      shedding converts NG2 into a diffusible entity able to interact with the growth
      cone, and we suggest that this release is likely to enhance its axon growth
      inhibitory activity.

PMID- 15866050
TI  - Synaptic localization of a functional NADPH oxidase in the mouse hippocampus.
AB  - Superoxide has been shown to be critical for hippocampal long-term potentiation
      (LTP) and hippocampus-dependent memory function. A possible source for the
      generation of superoxide during these processes is NADPH oxidase. The active
      oxidase consists of two membrane proteins, gp91phox and p22phox, and four
      cytosolic proteins, p40phox, p47phox, p67phox, and Rac. Upon stimulation, the
      cytosolic proteins translocate to the membrane to form a complex with the
      membrane components, which results in production of superoxide. Here, we
      determined the presence, localization, and functionality of a NADPH oxidase in
      mouse hippocampus by examining the NADPH oxidase proteins as well as the
      production of superoxide. All of the NADPH oxidase proteins were present in
      hippocampal homogenates and enriched in synaptoneurosome preparations.
      Immunocytochemical analysis of cultured hippocampal neurons indicated that all
      NADPH oxidase proteins were localized in neuronal cell bodies as well as
      dendrites. Furthermore, double labeling analysis using antibodies to p67phox and
      the presynaptic marker synaptophysin suggest a close association of the NADPH
      oxidase subunits with synaptic sites. Finally, stimulation of hippocampal slices
      with phorbol esters triggered translocation of the cytoplasmic NADPH oxidase
      proteins to the membrane and an increase in superoxide production that was
      blocked by inhibitors of NADPH oxidase. Taken together, our data suggest that
      NADPH oxidase is present in mouse hippocampus and might be the source of
      superoxide production required for LTP and memory function.

PMID- 15866051
TI  - Enteric neuroblasts require the phosphatidylinositol 3-kinase/Akt/Forkhead
      pathway for GDNF-stimulated survival.
AB  - Glial cell line-derived neurotrophic factor (GDNF)/Ret signaling is required for
      enteric neural crest survival, proliferation, migration and process extension,
      but signaling pathways that mediate enteric nervous system (ENS) precursor
      development are poorly understood. We therefore examined GDNF effects on
      immunoselected ENS precursor survival and neuronal process extension in the
      presence of phosphatidylinositol 3-kinase and mitogen-activated protein kinase
      pathway inhibitors. These studies demonstrated that GDNF promotes ENS precursor
      survival through phosphatidylinositol-3-kinase. Specifically, GDNF induces
      phosphorylation of Akt and loss of the Akt substrates FOXO1 and FOXO3a from the
      nucleus of ENS precursors. Furthermore, dominant negative Akt or active FOXO1
      constructs promote ENS precursor cell death while a dominant negative FOXO1
      construct prevents cell death. In contrast, the MAPK kinase inhibitor PD98059 did
      not influence ENS precursor survival or neurite extension. These data demonstrate
      a critical role for PI-3 kinase/Akt/FOXO signaling, but not for MAPK in ENS
      precursor survival and neurite extension.

PMID- 15866052
TI  - The epilepsy mutation, gamma2(R43Q) disrupts a highly conserved inter-subunit
      contact site, perturbing the biogenesis of GABAA receptors.
AB  - Given the association of a gamma2 mutation (R43Q) with epilepsy and the reduced
      cell surface expression of mutant receptors, we investigated a role for this
      residue in alpha1beta2gamma2 receptor assembly when present in each subunit.
      Regardless of which subunit contained the mutation, mutant GABA(A) receptors
      assembled poorly into functional cell surface receptors. The low level of
      functional expression gives rise to reduced GABA EC50s (alpha1(R43Q)beta2gamma2
      and alpha1beta2(R43Q)gamma2) or reduced benzodiazepine potentiation of GABA
      evoked currents (alpha1beta2gamma2(R43Q)). We determined that a 15-residue
      peptide surrounding R43 is capable of subunit binding, with a profile that
      reflected the orientation of subunits in the pentameric receptor. Subunit binding
      is perturbed when the R43Q mutation is present suggesting that this residue is
      critical for the formation of inter-subunit contacts at (+) interfaces of GABAA
      subunits. Rather than being excluded from receptors, gamma2(R43Q) may form non
      productive subunit interactions leading to a dominant negative effect on other
      receptor subtypes.

PMID- 15866053
TI  - Dopamine and noradrenaline control distinct functions in rodent microglial cells.
AB  - Microglial cells are the immune-competent elements of the brain. They not only
      express receptors for chemokines and cytokines but also for neurotransmitters
      such as GABA [Charles et al., Mol. Cell Neurosci. 24 (2003) 214], glutamate [Noda
      et al., J. Neurosci. 20 (2000) 251], and adrenaline [Mori et al.,
      Neuropharmacology 43 (2002) 1026]. Here we report the functional expression of
      dopamine receptors in mouse and rat microglia, in culture and brain slices. Using
      the patch clamp technique as the functional assay we identified D1- and D2-like
      dopamine receptors using subtype-specific ligands. They triggered the inhibition
      of the constitutive potassium inward rectifier and activated potassium outward
      currents in a subpopulation of microglia. Chronic dopamine receptor stimulation
      enhanced migratory activity and attenuated the lipopolysaccharide (LPS)-induced
      nitric oxide (NO) release similar as by stimulation of adrenergic receptors.
      While, however, noradrenaline attenuated the LPS-induced release of TNF-alpha and
      IL-6, dopamine was ineffective in modulating this response. We conclude that
      microglia express dopamine receptors which are distinct in function from
      adrenergic receptors.

PMID- 15866054
TI  - CaMKIIalpha enhances the desensitization of NR2B-containing NMDA receptors by an
      autophosphorylation-dependent mechanism.
AB  - Long-term potentiation or depression of synaptic function often requires Ca2+
      influx via NMDA-type glutamate receptors (NMDARs) and changes in the
      autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) at
      Thr286. Autophosphorylated CaMKII binds directly to NMDAR subunits, co-localizes
      with NMDARs in the postsynaptic density, and phosphorylates NR2B subunits at
      Ser1303. Here, we demonstrate that CaMKIIalpha enhances the extent and/or rate of
      desensitization of NMDA-induced macroscopic currents in HEK293 cells co
      expressing NR2B with either the NR1(011) or NR1(101) splice variants, without
      significantly changing other current parameters. In contrast, the extent of
      desensitization of NMDARs containing NR2A in place of NR2B is significantly
      decreased by co-expression of CaMKIIalpha. Kinases harboring K42R (inactive
      kinase) or T286A (autophosphorylation-deficient) mutations are defective in
      enhancing the desensitization of NR1/NR2B channels. In addition, the CaMKII
      dependent enhancement of NR1/NR2B channel desensitization is abrogated by
      intracellular loading with BAPTA. These data suggest a novel mechanism for Ca2+
      dependent negative-feedback regulation of NR2B-containing NMDARs in a CaMKII
      activity- and autophosphorylation-dependent manner that may modulate NMDAR
      mediated synaptic plasticity.

PMID- 15866055
TI  - Retinopathy and hypertension affect serum high-sensitivity C-reactive protein
      levels in Type 2 diabetic patients.
AB  - Several studies suggest that inflammation plays an important role in the
      pathogenesis of diabetes mellitus, as well as atherosclerosis, and acute-phase
      reactants have been proposed as monitors for the ongoing process of these
      diseases. We studied the clinical significance of serum high-sensitivity C
      reactive protein (hs-CRP) in relation to chronic diabetic complications using 114
      Japanese patients with Type 2 diabetes mellitus. The hs-CRP values were
      normalized by logarithmic transformation for statistical analysis. Retinopathy
      and hypertension were extracted as significant modulators for the hs-CRP value in
      the diabetic patients, in addition to previously known factors, age, and body
      mass index (BMI), by multivariate analysis. The hs-CRP level in normotensive
      diabetic patients without retinopathy was not significantly different from that
      of normal control participants after adjustment for age and BMI. The hs-CRP value
      was significantly high in the patients with hypertension, despite the existence
      or absence of diabetes. On the other hand, the hs-CRP level of the diabetic
      patients complicated with retinopathy was low especially in those with
      hypertension. The frequency of patients having an hs-CRP value above 1.0 mg/l who
      are thought to be at risk for cardiovascular diseases was also high in the
      patients complicated with hypertension and low in the diabetic patients with
      retinopathy. These results indicate that the presence or absence of hypertension
      and retinopathy should be taken into consideration for the interpretation of the
      serum hs-CRP in diabetic patients.

PMID- 15866056
TI  - Impact of insulin on microvascular blood flow and endothelial cell function in
      the postprandial state in patients with Type 1 diabetes.
AB  - The aim of the present study was to investigate postprandial microvascular blood
      flow following a standardized test meal in nondiabetic subjects and in patients
      with Type 1 diabetes after regular insulin or insulin lispro. In this open-label,
      randomised cross-over study, 20 nondiabetic participants and 20 patients with
      Type 1 diabetes were enrolled. To valuate the postprandial time course of skin
      microvascular blood flow, laser Doppler flux (LDF) readings were obtained at
      baseline and every 30 min following a standardized test meal. Furthermore, the
      microvascular response to acetylcholine (Ach) was measured, and blood was
      collected for the measurement of serum insulin and blood glucose levels. Patients
      with Type 1 diabetes received single doses of regular insulin or insulin lispro,
      respectively, in a randomised sequence, while in nondiabetics, no insulin
      substitution was performed. In nondiabetic participants, skin microvascular blood
      flow showed an early increase in LDF by median 6.0 arbitrary units (AU;
      interquartile range: 1.8-14.0 AU) within the first postprandial hour. The
      microvascular response to Ach also increased with a median response of 26.0 (19.0
      49.3) AU at 30 min pp and 50.0 (31.7-65.1) AU at 60 min pp. In patients with Type
      1 diabetes, the time course of postprandial LDF measurements observed after the
      administration of insulin lispro was nearly similar to the one observed in
      nondiabetic controls and differed from that after subcutaneous regular insulin
      treatment. The postprandial microvascular response to Ach was stronger following
      insulin lispro compared with regular insulin [30 min pp: 26.0 (19.0-49.3) vs.
      20.9 (9.7-26.1) AU, P=.0001]. Postprandial microvascular blood flow is disturbed
      in patients with Type 1 diabetes. Improvement of postprandial metabolic control
      was found to improve postprandial microvascular function.

PMID- 15866057
TI  - Prevalence of antiphospholipid antibodies is not different in Chilean diabetic
      patients and normal individuals.
AB  - Diabetes mellitus (DM) is complicated by vascular and neurological events.
      Antiphospholipid (aPL) antibodies have already been associated with many clinical
      conditions, including venous and arterial thrombosis, as well as recurrent fetal
      loss. However, a significant association between aPL antibodies and DM has not
      been widely reported yet. In the present study, we investigated the prevalence of
      aPL antibodies in diabetic patients. This study included 100 Chilean diabetic
      patients (67 of them with some complications and 33 without complications; 28
      with Type 1 and 72 with Type 2 DM) and 100 healthy blood donor controls. Each
      sample was analyzed for IgG, IgM and IgA anticardiolipin (aCL), anti-beta(2)
      glycoprotein I (anti-beta(2)GPI), antiprothrombin (aPT) antibodies, and lupus
      anticoagulant (LA). Fourteen out of 100 (14%) diabetic patients presented some
      type of aPL antibodies. Four patients were positive for aCL antibodies, two for
      anti-beta(2)GPI antibodies, and nine for aPT antibodies. All patients were LA
      negative. The incidence of different isotypes was similar in each of the aPL
      antibodies studied, and their activities were low. No significant correlation was
      observed between aPL antibodies and vascular complications.

PMID- 15866058
TI  - Bacteriological study of diabetic foot infections.
AB  - AIMS: The polymicrobial nature of diabetic foot infection has been well
      documented in the literature. Patients with diabetic foot infection not exposed
      to antibiotics are not well studied before. The relative frequency of bacterial
      isolates cultured from community-acquired foot infections that are not exposed to
      antimicrobial agents for 30 days is studied. In addition, the bacterial
      comparative in vitro susceptibility to the commonly used antibacterial agents is
      assessed. METHODS: This is a prospective study in which the infected wounds of 86
      consecutive diabetic patients seen in the diabetic foot clinic in Adan Teaching
      Hospital were cultured when visiting the clinic. The patients did not receive
      antimicrobial therapy 30 days prior to taking the cultures. The specimen was
      cultured using aerobic and anaerobic microbiological techniques. Isolates were
      tested for susceptibility to commonly used antimicrobial therapy. RESULT:
      Staphylococcus aureus was the most common isolate, being recovered from 38.4% of
      cases. Other organisms were Pseudomonas aeruginosa (17.5%) and Proteus mirabilis
      (18%), anaerobic gram-negative organisms (10.5%), mainly Bacteroides fragilis.
      Imipenem, meropenem, and cefepime were the most effective agents against gram
      negative organisms. Vancomycin was the most effective against gram-positive
      organisms. CONCLUSION: S. aureus and P. aeruginosa were the most common causes of
      diabetic foot infections. Anaerobic organisms are still a common cause for
      infection, although the prevalence is less. These wounds may require use of
      combined antimicrobial therapy for initial management.

PMID- 15866059
TI  - Protein oxidation in Type 2 diabetic patients on hemodialysis.
AB  - BACKGROUND: Oxidative stress is considered to be a unifying link between diabetes
      mellitus (DM) and its complications, including nephropathy. There have been many
      reports on increased production of oxidants and decreased level of antioxidants
      in diabetic patients. The dialysis procedure contributes to oxidative stress. An
      increase in oxidative stress may contribute to the development of oxidative
      protein damage in diabetic patients. Our aim was to reveal the effects of
      diabetes and hemodialysis (HD) on oxidative modifications of plasma proteins.
      METHODS: We measured reactive carbonyl derivates (PCO), protein thiol (P-SH), and
      reduced glutathione (GSH) levels in Type 2 diabetic (DM) and diabetic
      hemodialysed patients (DHD) and in healthy control participants. RESULTS: Protein
      carbonyl (PCO) content increased significantly in all patient groups relative to
      the controls. The dialysis procedure caused an additional increase in PCO levels
      in DHD patients before and after dialysis compared with the level in DM patients.
      There was a significant decrease in P-SH levels in DHD patients compared with the
      level in healthy participants and DM patients. There was no significant
      difference in the whole blood GSH levels between the DM patients and control
      participants. It was significantly higher in DHD patients in comparison to the DM
      patients. CONCLUSIONS: We conclude that PCO level increases in DM patients, and
      this increase is more profound in DHD patients, indicating that both diabetes and
      dialysis contribute to increased protein oxidation. The low P-SH level in DHD
      patients, but not in DM patients, suggests that dialysis is responsible for this
      decrease. We propose plasma PCO derivate as a novel specific marker for oxidative
      protein damage.

PMID- 15866060
TI  - Levels of plasma total adrenomedullin are related with two acute phase
      inflammatory reactants (fibrinogen and sialic acid) but not with markers of
      endothelial dysfunction in Type 1 diabetes Adrenomedullin and vascular risk
      factors in Type 1 DM.
AB  - Adrenomedullin (AM), an ubiquitous regulatory peptide with different actions, is
      known to be elevated in different clinical situations, including diabetes
      mellitus (DM), but its potential role in the pathogenesis of diabetic vascular
      complications is not clear. In the present study, we examined plasma total AM
      levels, and their association with different markers of endothelial dysfunction
      and with other established risk factors for cardiovascular diseases, in patients
      with Type 1 DM. We studied a total of 155 patients, 117 patients without any kind
      of vascular complications, 24 patients with retinopathy only, and 14 patients
      with retinopathy and microalbuminuria but normal renal function. None of them had
      clinical evidence of atherosclerotic disease. Compared with the control group (64
      healthy participants), patients had raised fibrinogen, soluble E-selectin ((s)E
      selectin), vascular cellular adhesion molecule (VCAM), angiotensin converting
      enzyme (ACE), and von Willebrand factor (vWf) (P<.001 in all cases), but plasma
      total AM, endothelin (ET), sialic acid, and homocysteine were not raised. In the
      diabetic group, AM levels correlated significantly with sialic acid (r=.16;
      P<.05), but a more significant correlation was found with fibrinogen (r=.30;
      P<.001). No correlation was found with the other parameters studied. In summary,
      plasma total AM levels seem to correlate with inflammatory markers but not with
      endothelial dysfunction markers in Type 1 diabetic patients without
      atherosclerotic disease.

PMID- 15866061
TI  - Effect of tequila on homocysteine, insulin secretion, insulin sensitivity, and
      metabolic profile in healthy men.
AB  - AIM: The purpose of this study is to identify the effect of a low dose of tequila
      on homocysteine, insulin secretion, insulin sensitivity, and metabolic profile in
      healthy young men. METHODS: An open clinical trial was carried out in eight
      healthy nonobese, young male volunteers. The study was divided in two phases. The
      first one evaluated metabolic changes, including insulin secretion and
      sensitivity due to acute administration of 30 ml of straight tequila. The second
      phase of the study evaluated metabolic effects due to the daily administration of
      30 ml of tequila during 30 days. RESULTS: There were no significant metabolic
      changes after the single oral administration of 30 ml of straight tequila. After
      the administration of tequila during 30 days, a significant increase in
      homocysteine levels and a tendency to increase the glucose concentration and to
      decrease the insulin sensitivity were found. CONCLUSION: Detrimental metabolic
      changes were observed with the daily administration of 30 ml of tequila during 30
      days.

PMID- 15866062
TI  - Evaluation of balance and physical fitness in diabetic neuropathic patients.
AB  - AIM: The main aim was to evaluate balance and physical fitness in diabetic
      neuropathic patients. METHODS: Sixty voluntary adults of both sexes from Kutahya,
      Turkey, were divided into two groups: a Type 2 diabetic neuropathic group (DG),
      mean age 57.6+/-3.9 (50-65; n=30); and a nondiabetic control group (CG), mean age
      55.6+/-6.1 (51-64; n=30). The CG was selected to match the diabetic group
      characteristics, such as age, body mass, and sex. Standing on dominant and
      nondominant leg, functional reach and physical fitness tests were used for
      assessment. RESULTS: Static and dynamic standings on one leg test were
      significantly lower in DG (P<.01). Considering CG results, maximal balance
      reduction in DG was found in the dynamic test on the dominant leg with the eyes
      open and head rotation (63.1%) and the lowest was on the static test on dominant
      leg with eyes open (19.7%). The result of the functional reach test was
      determined to be significantly lower in DG, with 21.3% balance reduction (P<.01).
      In all physical fitness tests, DG made significantly lower repetitions in 1 min
      (P<.01). Functional reach (34 cm) and one-leg standing (42 s) test results had
      shown our participants' low-risk falling, considering literature studies (15 cm
      and 30 s). CONCLUSION: The data show that the diabetic neuropathy disturbed
      especially the balance on the dominant leg and decrease physical fitness. In this
      situation, further studies that show the difference between dominant and
      nondominant leg balance and new risk of falling profile in diabetic neuropathic
      participants are needed.

PMID- 15866063
TI  - Superior segmental optic nerve hypoplasia and diabetes mellitus.
AB  - PURPOSE: The aim of this study was to describe the ocular findings of an 8-year
      old girl with bilateral superior segmental optic nerve hypoplasia (SSONH) whose
      mother had a history of Type 1 diabetes mellitus and to review the prior
      literature concerning this association. METHODS: Neuroophthalmic examination,
      including funduscopy, visual fields, optical coherence tomography, and magnetic
      resonance imaging (MRI) of the brain and orbits, were used. RESULTS: Bilateral
      inferior visual field defects prompted initial neuroophthalmic evaluation.
      Funduscopy revealed bilateral SSONH, worse on the right. MRI of the brain and
      orbits revealed hypoplastic optic nerves and a small optic chiasm. CONCLUSIONS:
      Although the association between SSONH and maternal diabetes mellitus is a well
      documented entity, prior reports have been solely in the neuroophthalmic
      literature. The optic discs in patients with SSONH have a characteristic
      appearance, which may obviate the need for additional evaluation of the visual
      field defects. The MRI findings of hypoplastic optic nerves and a small optic
      chiasm have previously not been reported. This patient underscores the importance
      of recognizing the association between SSONH and maternal diabetes mellitus.

PMID- 15866064
TI  - Thiazolidinediones-benefits on microvascular complications of type 2 diabetes.
AB  - Type 2 diabetes is associated with serious microvascular complications, such as
      nephropathy, retinopathy, and neuropathy, which have a significant impact on
      patients' quality of life, morbidity, and mortality. Type 2 diabetes management
      strategies to reduce the risk of microvascular complications include treatment of
      hyperglycaemia, hypertension, and other vascular risk factors. The importance of
      glycaemic control in reducing the risk of microvascular complications of diabetes
      is well established. However, many antihyperglycaemic therapies fail to provide
      adequate glycaemic control and do not prevent complications in the long term. The
      thiazolidinediones (TZDs) are a class of agents that provide sustained glycaemic
      control, mediated primarily by reductions in insulin resistance. Evidence
      reviewed suggests that the TZDs may have the potential to reduce microvascular
      complications through benefits that go beyond glycaemic control. Insulin
      resistance underlies a range of metabolic abnormalities, collectively known as
      the metabolic syndrome (MS), which are cardiovascular (CV) risk factors.
      Components include visceral obesity, hyperglycaemia, hypertension, dyslipidaemia,
      low-grade inflammation and microalbuminuria (an early manifestation of target
      organ damage). Reducing insulin resistance, therefore, has the potential to
      reduce both microvascular and macrovascular complications.

PMID- 15866065
TI  - Should minimal blood glucose variability become the gold standard of glycemic
      control?
AB  - The Diabetes Complications and Control Trial (DCCT) established glycosylated
      hemoglobin (A1C) as the gold standard of glycemic control, with levels </=7%
      deemed appropriate for reducing the risk of vascular complications. Yet, even
      when A1Cs were comparable between intensively treated subjects and their
      conventionally treated counterparts, the latter group experienced a markedly
      higher risk of progression to retinopathy over time. Our speculative explanation,
      based on the discovery that hyperglycemia-induced oxidative stress is the chief
      underlying mechanism of glucose-mediated vascular damage, was that glycemic
      excursions were of greater frequency and magnitude among conventionally treated
      patients, who received fewer insulin injections. Subsequent studies correlating
      the magnitude of oxidative stress with fluctuating levels of glycemia support the
      hypothesis that glucose variability, considered in combination with A1C, may be a
      more reliable indicator of blood glucose control and the risk for long-term
      complications than mean A1C alone.

PMID- 15866066
TI  - A 0.3-kb fragment containing the R-U5-5' leader sequence is essential for the
      induction of spongiform neurodegeneration by A8 murine leukemia virus.
AB  - Friend murine leukemia virus (Fr-MLV) clone A8 causes spongiform
      neurodegeneration in the rat brain. The A8-env gene is a primary determinant of
      neuropathogenicity, and the 1.5-kb ClaI-HindIII fragment containing the LTR and
      5' leader from A8 are additionally required for spongiosis. After replacement of
      the A8 enhancer region of the neuropathogenic chimera with the enhancer region of
      non-neuropathogenic 57, viral titer in the brain was reduced by two orders of
      magnitude. However, the A8 enhancer region was not responsible for the induction
      of spongiosis. The region responsible for neuropathogenesis was located in the
      0.3-kb KpnI-AatII fragment of A8 containing the R-U5-5' leader. The chimeric
      virus possessing this 0.3-kb fragment of A8 and the A8-env in the 57 background
      induced a high rate of spongiform neurodegeneration within 7 weeks (9/9 of
      infected rats). Studies using cultured cells suggest that the 0.3-kb fragment
      influences the expression of Env protein. Furthermore, these neuropathogenic
      chimerae, despite low viral replication in the brain, exhibited a stronger
      expression of Env protein compared with that of non-neuropathogenic viruses.

PMID- 15866067
TI  - Progression from productive infection to integration and oncogenic transformation
      in human papillomavirus type 59-immortalized foreskin keratinocytes.
AB  - Studies of changes in the virus and host cell upon progression from human
      papillomavirus (HPV) episomal infection to integration are critical to
      understanding HPV-related malignant transformation. However, there exist only a
      few in vitro models of both productive HPV infection and neoplastic progression
      on the same host background. We recently described a unique foreskin keratinocyte
      cell line (ERIN 59) that contains HPV 59 (a close relative of HPV 18). Early
      passages of ERIN 59 cells (passages 9-13) contained approximately 50 copies of
      episomes/cell, were feeder cell-dependent, and could be induced to differentiate
      and produce infectious virus in a simple culture system. We now report that late
      passage cells (passages greater than 50) were morphologically different from
      early passage cells, were feeder cell independent, and did not differentiate or
      produce virus. These late passage cells contained HPV in an integrated form. An
      integration-derived oncogene transcript was expressed in late passage cells. The
      E2 open reading frame was interrupted in this transcript at nucleotide 3351.
      Despite a lower viral genome copy number in late passage ERIN 59 cells,
      expression of E6/E7 oncogene transcripts was similar to early passage cells. We
      conclude that ERIN 59 cells are a valuable cell line representing a model of
      progression from HPV 59 episomal infection and virus production to HPV 59
      integration and associated oncogenic transformation on the same host background.

PMID- 15866068
TI  - In vitro selection of phage RB69 RegA RNA binding sites yields UAA triplets.
AB  - The SELEX method of in vitro selection was used to isolate RNAs that bind the
      RB69 RegA translational repressor protein immobilized on Ni-NTA agarose. After
      five rounds of SELEX, the pool of selected RNA displayed striking sequence
      uniformity: UAAUAAUAAUAAUA was clearly enriched in the 14 nucleotides that
      underwent selection. Individual, cloned molecules displayed a repeating (UAA)
      sequence, with only two RNAs having a 3' AUG. Removing the 3' AUG slightly
      reduced binding in gel shift assays, moving the AUG 5' proximal of the (UAA)
      slightly improved binding, but (UAA)4 alone still bound the purified protein.
      Dissociation constants showed that RNA shortened to (UAA)3 and (UAA)2 also
      retained binding, whereas cytosine clearly prevented binding by RB69 RegA.
      Scanning of RB69 gene starts and ends with an RB69 RegA SELEX information weight
      matrix yielded 21 sequences as potential RegA sites. One site, on the mRNA for
      the pentameric (4:1) phage gp44/62 DNA polymerase clamp loader complex, has the
      RB69 gene 44 stop codon and 3'-adjacent gene 62 initiation codon in a sequence
      (GAAAUAAUAUG) that is similar to in vitro selected RNA and was shown to bind RB69
      RegA. Sequences between the Shine-Dalgarno and initiation codon, which frequently
      contain a UAA stop codon of a 5'-adjacent gene, appear to be preferred RB69 RegA
      binding sites.

PMID- 15866069
TI  - Conserved serines in simian immunodeficiency virus capsid are required for virus
      budding.
AB  - The simian immunodeficiency virus (SIV) capsid protein (CA), a constituent of the
      Pr55Gag polyprotein, is phosphorylated in virions but not in virus-producing
      cells (Rue, S.M., Roos, J.W., Tarwater, P.M., Clements, J.E., Barber, S.A., 2005.
      Phosphorylation and proteolytic cleavage of gag proteins in budded simian
      immunodeficiency virus. J. Virol. 79 (4), 2484-2492.). Using phosphoamino acid
      analysis of CA, we show that serine is the primary phosphate acceptor. A series
      of substitution mutants of serines in the CA domain of Pr55Gag were constructed
      in the infectious viral clone SIVmac239. These virus mutants were examined for
      defects in virus replication and virion infectivity, release, and morphology, as
      well as alterations in phosphorylation of CA-containing proteins. Although the
      virus mutants exhibited a number of replication defects, none of these defects
      could be directly attributed to aberrant CA phosphorylation. A novel defect was a
      block in early budding, which was common among several virus mutants with
      substitutions in the CA N terminus. Together, these results indicate that certain
      residues in the CA N terminus are crucial for early budding events.

PMID- 15866070
TI  - Cross-inhibition to heterologous foot-and-mouth disease virus infection induced
      by RNA interference targeting the conserved regions of viral genome.
AB  - RNA interference (RNAi) is the process by which double-stranded RNA (dsRNA)
      directs sequence-specific degradation of messenger RNA in animal and plant cells.
      In mammalian cells, RNAi can be triggered by 21-23 nucleotide duplexes of small
      interfering RNA (siRNA). Strategies to inhibit RNA virus multiplication based on
      the use of siRNAs have to consider the high genetic polymorphism exhibited by
      this group of virus. Here we described a significant cross-inhibition of foot-and
      mouth disease (FMD) virus (FMDV) replication in BHK-21 cells by siRNAs targeted
      to various conserved regions (5'NCR, VP4, VPg, POL, and 3'NCR) of the viral
      genome. The results showed that siRNAs generated in vitro by human recombinant
      dicer enzyme gave an inhibition of 10- to 1000-fold in virus yield of both
      homologous (HKN/2002) and heterologous (CHA/99) isolates of FMDV serotype O at 48
      h post-infection (hpi). The inhibition extended to at least 6 days post
      infection. For serotype Asia1, the virus yield in YNBS/58-infected cells examined
      at 12, 24, and 48 hpi decreased by approximately 10-fold in cells pretreated with
      HKN/2002-specific siRNAs, but there was no significant decrease at 60 hpi. The
      inhibition was specific to FMDV replication, as no reduction was observed in
      virus yield of pseudorabies virus, an unrelated virus. Moreover, we also
      demonstrated an enhanced viral suppression could be achieved in BHK-21 cells with
      siRNA transfection after an infection had been established. These results
      suggested that siRNAs directed to several conserved regions of the FMDV genome
      could inhibit FMDV replication in a cross-resistance manner, providing a strategy
      candidate to treat high genetic variability of FMDV.

PMID- 15866071
TI  - A newly identified interaction between IVa2 and pVIII proteins during porcine
      adenovirus type 3 infection.
AB  - The adenovirus IVa2 is an intermediate viral gene product that appears to perform
      multiple essential roles in viral infection. Using IVa2 as bait in the yeast two
      hybrid system, we screened selected open reading frames (ORFs) of porcine
      adenovirus (PAdV)-3 for potential interaction with IVa2. Interestingly, pVIII
      showed specific interaction with IVa2. The yeast two-hybrid findings were
      validated by GST pull-down assays, in vitro binding studies employing cell-free
      coupled transcription-translation products and in vitro co-immunoprecipitations
      using protein-specific antibodies. Finally, we demonstrated that IVa2
      specifically interacts with pVIII during PAdV-3 infection.

PMID- 15866072
TI  - Characterization of neutralizing antibodies to West Nile virus.
AB  - We produced nine monoclonal antibodies (MAbs) directed against the West Nile
      virus E glycoprotein using three different immunization strategies: inactivated
      virus, naked DNA, and recombinant protein. Most of the MAbs bound to conformation
      dependent epitopes in domain III of the E protein. Four of the MAbs neutralized
      WNV infection and bound to the same region of domain III with high affinity. The
      neutralizing MAbs were obtained from mice immunized with inactivated virus alone
      or in combination with a DNA plasmid. In contrast, MAbs obtained by immunization
      with a soluble version of the E glycoprotein did not exhibit neutralizing
      activity. These non-neutralizing antibodies were cross-reactive with several
      other flaviviruses, including Saint Louis encephalitis, Japanese encephalitis,
      Yellow Fever and Powassan viruses. Interestingly, some non-neutralizing MAbs
      bound with high affinity to domains I or III, indicating that both affinity and
      the precise epitope recognized by an antibody are important determinants of WNV
      neutralization.

PMID- 15866074
TI  - Interaction of white spot syndrome virus VP26 protein with actin.
AB  - VP26 protein, the product of the WSV311 gene of white spot syndrome virus (WSSV),
      is one of major structural proteins of virus. In this study, when purified
      virions were treated with Triton X-100 detergent, VP26 protein was present in
      both the envelope and the nucleocapsid fraction. We have rationalized this
      finding by suggesting that VP26 protein might be located in the space between the
      envelope and the nucleocapsid. By using a fluorescent probe method, we have
      investigated the interaction between VP26 protein and some proteins of host
      cells. Three major VP26-binding proteins were purified from crayfish hemocytes by
      affinity-chromatography, in which the protein with an apparent molecular mass of
      42 kDa was identified as actin by mass spectrometry (MS). Moreover, the
      association of VP26 protein with actin microfilaments was confirmed by
      coimmunoprecipitation.

PMID- 15866073
TI  - A novel rudivirus, ARV1, of the hyperthermophilic archaeal genus Acidianus.
AB  - Virus ARV1, the first member of the family Rudiviridae infecting
      hyperthermophilic archaea of the genus Acidianus, was isolated from a hot spring
      in Pozzuoli, Italy. The rod-shaped virions, 610 +/- 50 nm long and 22 +/- 3 nm
      wide, are non-enveloped and carry a helical nucleoprotein core, with three tail
      fibers protruding at each end which appear to be involved in adsorption onto the
      host cell surface. The virions contain two protein components, a major one of
      14.4 kDa, which is glycosylated and a minor of about 124 kDa. The linear double
      stranded DNA genome yielded 24,655 bp of sequence, including 1365 bp inverted
      terminal repeats. Coding is on both strands and about 40% of the predicted genes
      are homologous to those of other hyperthermophilic crenarchaeal viruses, mainly
      rudiviruses. They include genes encoding the coat protein, two glycosyl
      transferases and a Holliday junction resolvase. Other assigned functions include
      a thymidylate synthase and three DNA-binding proteins. The genome sequence and
      composition differ strongly from those of the Sulfolobus rudiviruses SIRV1 and
      SIRV2, and the genome stability is very high, with no sequence variants being
      detected. Although the sequences of the inverted terminal repeats of the three
      rudiviruses are different, they all carry the motif AATTTAGGAATTTAGGAATTT near
      the genome ends which may constitute a signal for the Holliday junction resolvase
      and DNA replication.

PMID- 15866075
TI  - Encapsidation of minute virus of mice DNA: aspects of the translocation mechanism
      revealed by the structure of partially packaged genomes.
AB  - Minute virus of mice (MVM) packages a single, negative-sense copy of its linear
      single-stranded DNA genome, but a chimeric virus, MML, in which >95% MVM sequence
      was fused to the right-hand terminus of LuIII, packages >40% positive-sense DNA.
      While encapsidation of both MML strands begins efficiently, genome translocation
      frequently stalls at specific sites in positive-sense DNA. Internalized
      sequences, derived from the 3' end of the strand, ranged from 1 to 5 kb in
      length, with species of around 2 kb predominating. When nuclease activity during
      isolation was minimized, these truncated species were found to be part of pre
      excised 5 kb single-strands. Similarly, some partially encapsidated negative
      sense DNAs were observed, forming a continuum of protected 3' sequences between 1
      and 3 kb in length, but these were less abundant and more uniformly distributed
      than their positive-sense counterparts, indicating that the negative strand has
      evolved for efficient internalization. The paucity of protected DNAs shorter than
      1-2 kb suggests that translocation is biphasic, proceeding efficiently through
      the first (3') third of the genome, but prone to stall thereafter. Sequences with
      conspicuous secondary structure, including stem-loop and guanidine rich regions,
      were found to interrupt packaging, especially when positioned near the 5' end of
      the strand. Since VP2 amino-terminal peptides were exposed at the particle
      surface in all packaging intermediates, extrusion of this peptide precedes
      translocation of the full-length strand.

PMID- 15866076
TI  - Two residues in the hemagglutinin of A/Fujian/411/02-like influenza viruses are
      responsible for antigenic drift from A/Panama/2007/99.
AB  - The H3N2 vaccine strain (A/Panama/2007/99) for the 2003-2004 influenza season did
      not antigenically match the circulating A/Fujian/411/02-like H3N2 viruses and had
      reduced effectiveness against influenza outbreaks. A/Wyoming/03/2003, an A/Fujian
      like virus, was recommended as the vaccine strain for the 2004-2005 season.
      A/Wyoming differed from A/Panama by 16 amino acids in the HA1 molecule. Reverse
      genetics was used to determine the minimal amino acid changes that were
      responsible for the antigenic drift from A/Panama to A/Wyoming. After
      substitutions of 2 of the 16 amino acids in the HA (H155T, Q156H), the A/Panama
      HA variant was antigenically equivalent to A/Wyoming as determined by
      hemagglutination inhibition and microneutralization assays using ferret
      postinfection antisera. Conversely, A/Wyoming containing the His-155 and Gln-156
      residues from A/Panama was antigenically equivalent to A/Panama. These results
      indicated that only these two HA residues specified the antigenic drift from
      A/Panama to A/Wyoming; other amino acid differences between these two H3N2
      viruses had minimal impact on virus antigenicity but impacted virus replication
      efficiency in eggs.

PMID- 15866077
TI  - Identification of naturally occurring amino acid variations that affect the
      ability of the measles virus C protein to regulate genome replication and
      transcription.
AB  - The C protein of measles virus (MV C) is a basic protein of 186 amino acids (aa)
      that plays at least two roles in infected cells, interference with the innate
      immune response and modulation of viral polymerase activity. In this study,
      Northern blots were used to demonstrate that C proteins from three vaccine
      strains and three wild-type isolates of MV downregulated both mRNA transcription
      and genome replication in a plasmid-based mini-genome assay. The effect on
      transcription always paralleled the effect on replication; however, the six MV C
      proteins varied considerably in their ability to inhibit polymerase activity.
      Though the amino-terminal 45 aa of the C protein are more variable among
      different MV strains than the remaining 75% of the protein, the ability of the MV
      C proteins to inhibit polymerase activity was not regulated by substitutions in
      the amino terminus, but rather by the more conserved region containing aa 46-167.
      Naturally occurring substitutions at positions 147 and 166, but not 88 and 186,
      were found to regulate MV C protein activity. Deletion of the carboxyl-terminal
      19 aa did not affect the polymerase-modulating activity. Though we did not find a
      link between the aa changes in MV C and attenuation, these data provide new
      information regarding the functions of this non-structural protein.

PMID- 15866079
TI  - A historical perspective on pregnancy-related low back and/or pelvic girdle pain.
AB  - The growing interest in pregnancy-related low back and/or pelvic girdle pain has
      invoked research projects to this subject. Although it seems a modern syndrome,
      historical articles show that pregnancy-related pelvic girdle pain (PPGP) was
      already known centuries ago. The purpose of the present article is to provide a
      summary review of performed studies on pregnancy-related pelvic girdle pain.
      Remarkably, these studies show large differences in results with regard to, for
      example, incidence rates and relevant etiologic factors of pregnancy-related
      pelvic girdle pain. These differences can be explained by the use of different
      definitions and descriptions of pregnancy-related pelvic girdle pain between
      studies. In conclusion, it is necessary to search for an evidence-based overall
      definition of pregnancy-related pelvic girdle pain in order to provide more
      knowledge about incidence rates, etiologic factors and other related subjects.

PMID- 15866080
TI  - How unexpected are unexpected findings in prenatal cytogenetic diagnosis? A
      literature review.
AB  - The objective of this review was to gain understanding about unexpected findings
      in prenatal cytogenetic diagnosis. This category of results might be excluded
      from prenatal testing when new molecular tests such as I-FISH and QF-PCR will be
      applied in a future scenario of targeted testing. The literature was
      systematically searched for publications wherein the term unexpected or a synonym
      refers to testing results with specific problems. On the selected articles a
      qualitative analysis was performed, using the methods of cross-case analysis and
      within-case analysis. Sixteen articles published between 1979 and 2003 were
      selected. Analysis led to the classification of four problems of unexpected
      findings: I. unexpected for professionals; II. unexpected for patients; III.
      uncertainty; IV. other difficult counselling issues. We conclude that currently
      the problems of unexpected findings relate only slightly to their unexpected
      character. Instead, the main problems of unexpected findings relate to
      uncertainty and other aspects which create difficult counselling issues. As such,
      unexpected findings can be distinguished only gradually from standard results.
      Before targeted testing can be applied it is necessary to establish exact
      criteria in order to discern unexpected findings from standard testing results.

PMID- 15866081
TI  - Early antiplatelet and antithrombotic therapy in patients with a history of
      recurrent miscarriages of known and unknown aetiology.
AB  - OBJECTIVES: To assess the efficacy of early thromboprophylaxis throughout
      pregnancy in women with previous history of first trimester recurrent
      miscarriages of unknown aetiology. METHODS: Low dose aspirin and low molecular
      weight heparin (LMWH) were administered from the day of detection of the fetal
      heart up to the 37th week, in two groups of patients of known (Group A, n = 24)
      and unknown aetiology recurrent miscarriages (Group B, n = 27). RESULTS: The
      success rate (viable pregnancy >24 weeks) was high and equally effective in both
      Groups A and B (83.3% and 85.1%, respectively). The complications recorded (pre
      eclampsia, IUGR, placenta abruptio, injection site heamatomas and skin reactions)
      were more prevalent in Group A but of no significant difference. No abnormal
      bleeding was observed during vaginal delivery or caesarean section. CONCLUSIONS:
      Our results reaffirm previous reports that the use of LMWH in combination with
      low dose aspirin throughout pregnancy is safe and effective. It was also shown
      that the treatment is equally effective against recurrent miscarriages in both
      groups of patients, of known and unknown aetiology.

PMID- 15866082
TI  - The use of biochemical markers in prenatal diagnosis of intrauterine growth
      retardation: insulin-like growth factor I, Leptin, and alpha-fetoprotein.
AB  - OBJECTIVE: To determine the relation between weight deficit at birth and IGF-I,
      IGFBP-I, Leptin, and AFP levels in amniotic fluid after 14-18 weeks; to assess
      the diagnostic usefulness of these biochemical markers. STUDY DESIGN:
      Longitudinal, prospective study. Amniocentesis was performed in pregnant women
      after 14-18 weeks of gestation. STUDY POPULATION: 86 controls, 18 IUGR <10
      percentile, and 17 IUGR <5 percentile. RESULTS: No significant correlation was
      found between severity of IUGR and IGF-I, IGFBP-I, or Leptin. AFP was inversely
      correlated with severity of IUGR; results for the IUGR <10 percentile were: S:
      65.7%, SP: 56.9%, PPV: 38.3%, NPV: 80.3%, and an overall diagnostic capacity of
      65.6%. Results for the IUGR <5 percentile were: S: 76.4%, SP: 54.8%, PPV: 21.6%,
      NPV: 93.4% were obtained, and an overall capacity of 70.6%. CONCLUSIONS: Elevated
      values of AFP in amniotic fluid may help early detection of populations at risk
      of developing IUGR.

PMID- 15866083
TI  - Increased plasma levels of Urotensin-II in preeclampsia-eclampsia: a new mediator
      in pathogenesis?
AB  - OBJECTIVE: To assess the possible role of human Urotensin-II (hU-II), a
      vasoactive peptide, in the pathophysiology of preeclampsia-eclampsia
      prospectively. STUDY DESIGN: Sixty subjects, 30 with a diagnosis of preeclampsia
      eclampsia (group I) and 30 control subjects (group II), who had been admitted
      between January, 2002 and December, 2002, were taken into the study. Patients in
      group I had an increase in blood pressure after 28th week of gestation, without
      any history of hypertensive disease and/or preeclampsia or eclampsia. hU-II
      levels were assessed using a radioimmunoassay method. RESULTS: No statistically
      significant difference in terms of age, gestational age, gravidity, abortion and
      parity was detected among groups (P > 0.05). Plasma hU-II levels in the
      preeclampsia-eclampsia and control groups were 10.11 +/- 5.94 pg/mL and 3.93 +/-
      1.73 pg/mL, respectively. Difference between plasma hU-II levels of the two
      groups was found to be statistically significant (P < 0.00001). Also there was
      correlation between hU-II levels and mean arterial pressures in both groups (r =
      0.73, P < 0.0001 and r = 0.72, P < 0.0001 for groups I and II, respectively).
      CONCLUSION: Results of our study strongly suggest an important role for hU-II in
      the pathophysiology of preeclampsia-eclampsia. Further studies concerning
      placenta and cord blood samples will more clearly elucidate the role of Urotensin
      II in the pathogenesis of preeclampsia-eclampsia, and its feto-maternal effects.

PMID- 15866084
TI  - Gestational diabetes in a high-risk population: using the fasting plasma glucose
      to simplify the diagnostic algorithm.
AB  - OBJECTIVE: To evaluate the value of fasting plasma glucose (FPG) in screening a
      high-risk population for gestational diabetes mellitus (GDM). STUDY DESIGN:
      During an 8-month period, 1685 pregnant women underwent the one-step 75 g oral
      glucose tolerance test (OGTT) as a part of a universal screening program. The
      receiver operating characteristic (ROC) curve was used to analyze the performance
      of the FPG. RESULTS: 333 (19.8%) women had GDM (WHO criteria). The area under the
      ROC curve of FPG to detect GDM was 0.639 (95% CI 0.603-0.674), which reflected
      the degree of the FPG histogram overlap in women with and without GDM. A FPG
      threshold of 4.7 mmol/l reached the minimally acceptable sensitivity of 78.1%
      with a corresponding unacceptable specificity of 32.2%. 508 (31%) women were
      below this threshold, at a negative predictive value of 85.6%. The FPG at higher
      thresholds with acceptable specificity had poor sensitivity and positive
      predictive value to be useful. CONCLUSION: Though the high false positive rate at
      any FPG threshold with adequate sensitivity makes the FPG an inappropriate test
      for GDM screening, the FPG has the potential to avoid nearly one-third of the
      cumbersome OGTTs at the expense of missing one-fifth of pregnant women with
      milder GDM.

PMID- 15866085
TI  - Polymorphisms of genes involved in homocysteine metabolism in preeclampsia and in
      uncomplicated pregnancies.
AB  - OBJECTIVE: To evaluate the possible relationship between preeclampsia and
      polymorphisms in the main genes involved in folate-homocysteine metabolism. STUDY
      DESIGN: Case-control study: 43 patients with preeclampsia and 122 controls
      without pregnancy complications. Laboratory studies: tHcy and other amino acids,
      folate and vitamin B(12) and polymorphisms: 677C > T and 1298A > C (MTHFR); 699C
      > T, 844ins68 and 1080C > T (CBS); 2756A > G (MTR); and 66G > A, IVS1+766G > A
      and IVS1+754A > C (MTRR). RESULTS: Plasma tHcy and folate values were
      significantly higher (P = 0.004 and P = 0.019), while Met/tHcy ratios were lower
      (P < 0.001) in the patients compared with controls. No association was observed
      between polymorphisms tested and preeclampsia. In the control group, four such
      associations were found: the 1298A > C polymorphism (MTHFR) with the ratio
      Met/tHcy (P = 0.014); the 699C > T polymorphism (CBS) with the ratio tHcy/SigmaAA
      (P = 0.013); the 2756A > G polymorphism (MTR) with tHcy (P = 0.034); and the
      IVS1+766G > A polymorphism (MTRR) with hyperhomocysteinemia (P = 0.012).
      CONCLUSION: An association between the polymorphisms analysed and preeclampsia
      could not be demonstrated.

PMID- 15866086
TI  - Early oral hydration and its impact on bowel activity after elective caesarean
      section--our experience.
AB  - AIM: To assess the effects of early oral hydration after elective caesarian
      section. METHODS: Hundred women were selected from the maternity wards of LHMC
      and SSK Hospital, and alternately assigned into control and study groups of 50
      each. Women with medical complications and antepartum haemorrhage were excluded.
      In the study group, oral hydration was started 6-h postextubation irrespective of
      presence of bowel sounds. Solid food was started after bowel sounds appeared. In
      the control group, traditional regime of oral hydration after the appearance of
      bowel sounds and then a gradual shift to the solids was adopted. The return of
      bowel activity, time of ambulating and complications were compared. RESULTS:
      Bowel sounds appeared in a significantly shorter duration of time in study group,
      the mean being 7.4 h as compared to 11.5 h in the control group. Passage of
      flatus and bowel evacuation was earlier in the study group (9.14 and 23.7 h,
      respectively) than in the control (19.9 and 32.3 h, respectively). Women
      ambulated faster in the study group than the control group (15 h versus 25 h,
      respectively). Mean oral fluid intake was much more and return to soft and then
      full diet was faster in the study group. Sixty percent women preferred early
      feeding to the traditional one. CONCLUSION: Early oral hydration in the
      postoperative period helps in the faster recovery of the patient by means of
      quicker return to normal feeding habits and early ambulation, the two main
      concerns of any surgeon before discharging the woman after caesarian section.

PMID- 15866087
TI  - Peripartum hysterectomy in a teaching hospital in the eastern region of Turkey.
AB  - OBJECTIVES: The aim of this study was to find the incidence and clinical
      implications of peripartum hysterectomy in our hospital at the Eastern region of
      Anatolia. STUDY DESIGN: We analyzed retrospectively all cases of peripartum
      hysterectomy performed at YYU Medical Faculty Hospital between January 1995 and
      April 2003. Emergency peripartum hysterectomy was performed for hemorrhage which
      cannot be controlled with other conventional treatments within 24h of a delivery.
      There were 24 cases of emergency peripartum hysterectomy performed. RESULTS: The
      incidence of emergency peripartum hysterectomy was 5.09 per 1000 deliveries. Half
      of the hysterectomies followed cesarean section. Eleven patients were referred to
      our clinics from other hospitals. Uterine atony (45.8%) was the most common
      indication and placenta accreta (25.0%) was the second most common. Eighteen
      patients (75%) had subtotal hysterectomy. Bladder injury was seen in three cases.
      Re-exploration was performed in three cases (12.5%). Seventeen patients stayed in
      hospital over 7 days. There were four (16.7%) maternal deaths all of whom were
      referred from other hospitals. CONCLUSION: The mortality and morbidity of
      performing a peripartum hysterectomy is elevated, especially if performed in
      critical patients referred from other hospitals.

PMID- 15866088
TI  - Statins have additive effects to vertebral bone mineral density in combination
      with risedronate in hypercholesterolemic postmenopausal women.
AB  - BACKGROUND: Recent data suggest that statins used in the treatment of
      hypercholesterolaemia decrease fracture risk. In this study, we aimed to
      investigate prospectively whether statins have an additive effect to
      bisphosphonates (risedronate) according to the primary hypothesis that the
      addition of atorvastatin to risedronate would produce an increase, from baseline,
      in lumbar vertebrae and total hip BMD that was greater than that observed with
      risedronate alone. METHODS: A total of 120 hypercholesterolaemic postmenopausal
      women with osteoporosis or osteopenia were randomized to receive risedronate (5
      mg/day) or risedronate (5 mg/day) plus atorvastatin (20 mg/day). Changes in bone
      mineral density in the lumbar spine and hip, and serum lipid and glucose
      metabolism changes were assessed. RESULTS: Compared with risedronate alone, at 6
      months, risedronate plus atorvastatin produced significantly greater increases in
      the bone mineral density of the lumbar spine (1.58% versus 0.75%, p < 0.05). We
      found no difference after therapy in BMD of the total hip (1.2% versus 1.1%).
      Risedronate plus atorvastatin therapy had favorable effects on the serum lipid
      profile: LDL and total cholesterol. Serum fasting glucose and HbA1c levels were
      not affected during the treatments. CONCLUSION: Statins have modest additive
      effects to bisphosphonates in improving lumbar spine bone mineral density in
      hypercholesterolaemic postmenopausal women with established osteoporosis
      osteopenia. A long-term study with adequate sample size is necessary to assess
      the effects of statins -- in combination or alone -- on the bones and prevention
      of fractures.

PMID- 15866089
TI  - Comparison between "short" and "long" protocols in an ICSI programme.
AB  - In the present retrospective study we compare the efficacy of gonadotropin
      releasing hormone (GnRH) agonist in a long protocol and a GnRH agonist in a short
      protocol administration for controlled ovarian hyperstimulation (COH) in an ICSI
      program. A total of 424 consecutive patients with a history of male factor were
      included in the present study. Three hundred and three patients were included in
      the long protocol and 121 in the short protocol. Patients treated with the short
      protocol were stimulated in a shorter time and achieved lower estradiol levels. A
      significantly higher percentage of oocytes transferred were found in the long
      protocol. The clinical pregnancy rate per embryo transfer was 39.3% in the long
      protocol and 19.2% in the short protocol (p=0.001).

PMID- 15866090
TI  - Magnetic resonance spectroscopic comparison of the effects of resveratrol (3,4',5
      trihydroxy stilbene) to conjugated equine estrogen, tibolone and raloxifene on
      ovariectomized rat brains.
AB  - OBJECTIVE: To investigate the effects of resveratrol on basic cerebral
      metabolites of in the brains of ovariectomized rats. MATERIALS AND METHODS:
      Twenty-four bilaterally ovariectomized rats were randomly assigned into six
      groups with four rats in each group. The groups consisted of sham-operated
      (control), ovariectomized, resveratrol, conjugated equine estrogen (CEE),
      tibolone and raloxifene treated rats. Drug administration started at the 5th day
      following ovariectomy and continued for 35 days. At the end of the entire course,
      in vivo single voxel magnetic resonance spectroscopy was performed on whole
      brains to determine choline, creatine and N-acetyl aspartate (NAA)
      concentrations. RESULTS: Compared to sham-operated group, ovariectomized group
      had significantly lower NAA (P<0.008) but significantly higher choline levels
      (P<0.031). Administration of CEE and resveratrol resulted in NAA levels that were
      similar to those in the sham-operated group, showing that the NAA decrease due to
      ovariectomy was prevented. Treatment with tibolone and raloxifene resulted in a
      smaller increase in NAA and the effect failed to reach significance.
      Administration of resveratrol, CEE, tibolone and raloxifene resulted in choline
      levels similar to those in sham-operated group, showing that the increase in the
      ovariectomy group was prevented. CONCLUSION: Resveratrol causes levels of
      cerebral metabolites that is similar to conventional hormone replacement agents.
      This finding may suggest that neuronal function in the postmenopausal state was
      preserved. More detailed investigation of this issue should be the task of future
      research.

PMID- 15866091
TI  - Enzymatic digestion plus mechanical searching improves testicular sperm retrieval
      in non-obstructive azoospermia cases.
AB  - BACKGROUND: In non-obstructive azoospermic patients (NOA) besides the mechanical
      treatment, vital spermatozoa from the tissue obtained from testes by biopsy can
      be enzymatically prepared. OBJECTIVE: To increase the sperm recovery success of
      testicular sperm extraction (TESE), suitable for ICSI. STUDY DESIGN: Prospective,
      clinical study. In 177 consecutive men who presented with clinical and laboratory
      data indicating NOA, tissue samples were obtained by microdissection TESE method.
      Initially, mature spermatozoa were searched for by mechanical extraction
      technique shredding the biopsy fractions. In cases with no spermatozoa was
      observed after maximum 30 min of initial searching under the inverted microscope,
      the procedure was then followed by enzymatic digestion using DNAse and
      collagenase type IV. In cases of at least a mature spermatozoon could be obtained
      properly, ICSI was performed. RESULTS: Of 177 cases with NOA, conventional
      mincing method extended with enzymatic treatment yielded successful sperm
      recovery for ICSI in 102 (57%). Overall in vitro tissue-processing time for
      patients with sperm recovery failure after 30 min of mechanical searching, was
      between 80 and 105 min (mean 96+/-9). Cleavage, embryo transfer and clinical
      pregnancy rates in mechanical plus enzymatic TESE patients were not significantly
      different from those of only mechanically TESE performed patients (p>0.05).
      CONCLUSION: Combination of conventional TESE and enzymatic digestion is an
      effective method to recover spermatozoa suitable for ICSI. The benefit of the
      mincing combined with enzyme to sperm retrieval for NOA is firstly to shorten the
      mechanical searching time, thus minimizing further cellular damage as well as
      exposure to external conditions, and secondly to reduce the number of cases with
      sperm recovery failures.

PMID- 15866092
TI  - Serum lipids concentration in women with benign and malignant ovarian tumours.
AB  - Early diagnosis can improve clinical effects of ovarian carcinoma treatment.
      Until now, a satisfying screening method has not been found. Serum lipid and
      lipoprotein association with neoplasm is already established. In our study, we
      have examined concentration of total cholesterol, free cholesterol, HDL
      cholesterol, HDL3 and HDL free cholesterol fraction, triglycerides, and
      apolipoproteins: AI, AII and B and aimed to prepare the most likely model of
      lipid profile in women suffering from ovarian neoplasm. The serum lipid
      parameters were analysed in 91 operated patients: 64 with ovarian malignant
      tumour, 27 with benign ovarian cysts and 44 apparently healthy age-matching pair
      women as a control group. THE RESULTS: concentration of two parameters:
      apolipoprotein AI and free cholesterol allows for excluding ovarian neoplasm in
      95.5%; examination of six parameters: apolipoprotein AI, free cholesterol, HDL
      free cholesterol, HDL total cholesterol, apolipoprotein B and HDL3 fraction
      allows for diagnosing ovarian malignancy with 97% probability. This probability
      does not depend on staging of cancer, patient's age, nor BMI. No statistically
      significant difference between malignant and benign ovarian tumour has been
      confirmed.

PMID- 15866093
TI  - Modified vulvar vestibulectomy: simple and effective surgery for the treatment of
      vulvar vestibulitis.
AB  - OBJECTIVE: To evaluate the success of a simple modified vestibulectomy in
      treating vulvar vestibulitis. STUDY DESIGN: Fifty-nine patients with vulvar
      vestibulitis refractory to nonsurgical treatment underwent modified
      vestibulectomy. Response was defined as return to normal coitus and was graded as
      complete, partial or non-responsive. RESULTS: The postoperative follow-up period
      was 6 months-10 years. Thirty-nine (73.6%) patients reported complete response, 7
      (13.2%) had partial response, and 7 (13.2%) were non-responsive to surgery.
      CONCLUSION: Surgery is an effective treatment for vulvar vestibulitis refractory
      to conservative treatment. Simple modified vestibulectomy is considerably less
      invasive, technically simpler and probably less time consuming. Postoperative
      results employing this surgical procedure are found to be in line with
      postoperative results reported by others who employ surgical methods that are
      more extensive.

PMID- 15866094
TI  - Light and electron microscope examination of the effects of methotrexate on the
      endosalpinx.
AB  - OBJECTIVE: To examine the effects of increasing doses of methotrexate (Mtx) on
      the fallopian tubes. STUDY DESIGN: The study was carried out on 24 female rats
      (Albino Wistar type, 250-300 g). The rats were randomly divided into four groups
      of six. Different doses of Mtx were given to the rats by i.p. injection: 1mg/kg
      to those in group 1, 5mg/kg in group 2 and 10 mg/kg in group 3. Rats in group 4
      received injections of physiological serum only and were treated as the control
      group. Ten days after the injection, the fallopian tubes of the rats were removed
      for examination separately by light and electron microscopy (EM) for comparison.
      RESULTS: Light microscopy showed that in group 1 the surface epithelial cells
      were normal and the lamina propria was infiltrated by numerous inflammatory cells
      with a prevalence of polymorphonuclear leucocytes. Findings in groups 2 and 3
      were similar: the lamina propria was infiltrated with granulocytes in one
      specimen from each of the two groups, and granulocytes were also observed among
      epithelial cells. In the control group all surface structures were found to be in
      a normal condition. Electron microscopy showed cilial loss in the epithelial
      cells and central crystolysis in mitochondria in all group 1 specimens. Findings
      in groups 2 and 3 were similar. The cytoplasm of the epithelial cells seemed to
      be dense, there was prominent crystolysis (crystalloid formation) in the
      mitochondria, and vacuolisation (vacuole formation) in the cytoplasm seemed to be
      augmented. Cilial loss was prominent, and the basal membrane was irregular.
      Epithelial cell nuclei were in disorder. Lipid granules were observed extensively
      in epithelial cells. Eosinophils seemed to be dominant in connective tissues
      below the epithelium. In all control group specimens the epithelium seemed to be
      normal with all organelles in place; the condition of intercellular junctions,
      ciliated epithelium and all mitochondria also seemed to be normal, and the basal
      membrane was observed to be in order. CONCLUSION: In view of these findings, we
      conclude that the ultrastructural derangements resulting from administration of
      Mtx in doses in excess of 1mg/kg can cause a reduction in the surface
      epithelium's ability to make rhythmic lashing movements and can impair the
      patency of the fallopian tubes. All these disturbances could be involved to some
      degree in the causation of infertility and recurrent ectopic pregnancy.
      Therefore, the dosage of Mtx should be limited to use of the lowest effective
      dose to avoid these adverse effects.

PMID- 15866095
TI  - Ovarian cysts in tamoxifen-treated women with breast cancer.
AB  - OBJECTIVE: The objective of this study was to detect any ovarian changes in
      tamoxifen-treated breast cancer patients. METHODS: In all, 51 patients with
      breast cancer were enrolled in the study, which was conducted in the SSK (Social
      Security Agency) Aegean Maternity Hospital between January 1999 and December
      2002. The patients' demographic and medical data were reviewed. All patients
      taking part in the study received tamoxifen therapy, but the duration was not
      uniform. Gynecological examination and transvaginal ultrasonography (TVU) were
      performed in each case. Any ovarian cysts or masses were identified, and serum Ca
      125 levels were recorded. RESULTS: Of the 51 tamoxifen-treated patients enrolled
      in this study, 24 were still premenopausal and 27 were postmenopausal when they
      were monitored for breast cysts during the tamoxifen treatment started after the
      diagnosis of breast cancer. Their average age was 53.7 (range 31-64) years. The
      mean duration of tamoxifen therapy was 23.5 (range 8-49) months. Ovarian cysts
      were diagnosed in nine (17.6%) patients and required surgery in two of these;
      pathological examination revealed serous cysts of the ovary in both. CONCLUSION:
      : In cases with ovarian cyst formation during tamoxifen treatment of breast
      cancer, discontinuation of tamoxifen followed by monitoring is quite a reasonable
      way to proceed in most cases. Surgical intervention should be carried out when
      cysts are >5 cm in diameter.

PMID- 15866096
TI  - Genetic imbalances in endometrial hyperplasia and endometrioid carcinoma detected
      by comparative genomic hybridization.
AB  - OBJECTIVE: To evaluate the sequential genomic copy alterations related to the
      development of precursor lesions and endometrioid-type endometrial carcinomas,
      and its association with cellular atypia. STUDY DESIGN: Paraffin-embedded tissue
      specimens from 32 cases of endometrial hyperplasia, 15 of endometrial carcinoma,
      and 20 of normal endometrial tissue were retrospectively evaluated by the
      comparative genomic hybridization (CGH) technique. The average number of copy
      alterations (ANCA) index was used to define the incidence of genomic imbalances
      in each tissue group. Identified sequential genetic abnormalities were compared
      with the final histopathological diagnosis and the cellular atypia. RESULTS:
      Detectable and consistent chromosomal imbalances were found in 13 hyperplasia and
      9 carcinoma specimens. There was a significant correlation between ANCA value and
      degree of cellular atypia and tumor grade. While 1p36-pter, 20q deletions, and 4q
      overrepresentation were the most prevalent imbalances detected in both complex
      hyperplasia and complex atypical hyperplasia, 17q22-qter deletion and
      amplification of 2p34 were only seen in hyperplasia with atypical cells.
      Overrepresentations of chromosomes 8q, 1q, and 3q are the most frequent
      aberrations in endometrial carcinomas, but were absent from all the precursor
      lesions except one. Underrepresentations of chromosomes 1p36-pter and 10q are the
      other commonly seen aberrations in carcinomas, the latter being more frequent in
      moderately differentiated than in poorly differentiated lesions. CONCLUSIONS:
      Different patterns of chromosomal aberrations are seen in precursor lesions than
      in endometrial carcinomas, except for the loss of 1p36-pter. The presence of 1p
      deletion in both endometrial hyperplasia and cancer specimens suggests that this
      is an early event in the development of carcinoma. These results support a
      stepwise mode of tumorigenesis with accumulation of a series of genomic copy
      alterations in endometrial carcinogenesis.

PMID- 15866097
TI  - Atrioventricular block in preterm infants caused by hypocalcaemia: a case report
      and review of the literature.

PMID- 15866098
TI  - Impairment of cardiac function in a successful full-term pregnancy in a
      homozygous beta-thalassemia major: does chelation have a positive role?

PMID- 15866100
TI  - Comment on the article "Acute pulmonary oedema during nicardipine therapy for
      premature labour. Report of five cases" by Vaast P., et al. [Eur J Obstet Gynecol
      Reprod Biol 2004;113:98-9].

PMID- 15866101
TI  - An additional approach of repeat digital examination for preterm labor. Comment
      on Volumenie et al. [Eur J Obstet Gynecol RB 117 (2004) 33-7].

PMID- 15866102
TI  - Suicide risk during pregnancy. Comment on "The obstetrician and depression during
      pregnancy" by Campagne DM [Eur J Obstet Gynecol Reprod Biol 116 (2) (2004) 125
      30].

PMID- 15866104
TI  - Depression and pregnancy--may selective serotonin reuptake inhibitors be
      associated to behavioural teratogenicity? Comment on "The obstetrician and
      depression during pregnancy" by Campagne DM [Eur J Obstet Gynecol Reprod Biol 116
      (2) (2004) 125-30].

PMID- 15866107
TI  - Predictive value of maternal serum and vaginal interleukin-6 levels in preterm
      labor.
AB  - OBJECTIVE: The aim of the current study was to evaluate the predictive value of
      maternal serum and vaginal interleukin 6 (IL-6) levels for preterm delivery
      before 37 gestational weeks in patients with preterm labor and to determine the
      probable relationship between IL-6 concentrations and delivery interval. METHODS:
      In this prospective study, maternal serum and vaginal IL-6 levels were measured
      in 40 patients with the diagnosis of preterm labor between the 28th and 36th
      gestational weeks (study group) and in 20 pregnant women between the same
      gestational weeks attending the antenatal clinic with no complaints (control
      group). The gestational age at the time of admission and delivery, as well as the
      delivery interval, were evaluated and compared with the concentration of IL-6 on
      admission. RESULTS: There were no significant relationships between maternal
      serum concentrations of IL-6 and preterm delivery. Vaginal IL-6 levels were
      significantly higher in the study group as compared with the control group (P <
      .001). The optimal cut-off value for vaginal IL-6 (172 pg/mL) gave a sensitivity
      level of 73.9% (95% confidence interval [CI], 67-82%) at a specificity of 100%
      (95% CI, 91-100%) with positive and negative predictive values of 94.1% and
      83.7%, respectively. In the study group, the interval from collection to delivery
      was significantly shortened when the maternal vaginal IL-6 levels increased.
      CONCLUSION: The ease of measurement, feasibility, cost-effectiveness, and success
      of identifying pregnancies at risk for preterm labor with vaginal IL-6 make this
      a useful biochemical marker for preterm labor and delivery.

PMID- 15866108
TI  - Does reduction of circulating prostaglandin E2 reduce fetal hypothalamic
      pituitary-adrenal axis activity?
AB  - OBJECTIVE: Placental production of prostaglandin E2 (PGE2) increases in fetal
      sheep as term approaches. It has been suggested that placental PGE2 may act as a
      hormone to activate the fetal hypothalamic-pituitary-adrenal (HPA) axis.
      Alternatively, we have proposed that local generation of prostaglandins in the
      fetal brain and/or pituitary might play a more prominent role in the stimulation
      of fetal adrenocorticotropin (ACTH) secretion. We performed the present
      experiments to test the hypothesis that the elevated concentrations of PGE2 in
      fetal plasma do not tonically stimulate fetal ACTH secretion. METHODS: We studied
      chronically catheterized late-gestation fetal sheep. Selective inhibitors of
      prostaglandin synthase-1 and -2 (PGHS-1 and PGHS-2) were injected intravenously.
      Fetal blood pressure and heart rate were monitored continuously, and circulating
      concentrations of PGE2, ACTH, and cortisol were measured by specific immunoassay.
      RESULTS: Injection of vehicle did not have an effect on circulating levels of
      PGE2 or ACTH, but it did have a mild stimulatory effect on cortisol. The
      selective PGHS-2 inhibitor, Nimesulide (Cayman Chemical, Ann Arbor, MI),
      significantly decreased plasma PGE2 concentrations. The selective PGHS-1
      inhibitor, Resveratrol (Cayman Chemical), produced smaller decreases in plasma
      PGE2 concentrations and significantly increased mean arterial blood pressure.
      Neither inhibitor significantly altered plasma ACTH or cortisol concentrations.
      CONCLUSION: These results demonstrate that reduction of circulating PGE2
      concentrations in response to intravenous injection of PGHS-1 and PGHS-2
      inhibitors does not reduce fetal HPA axis activity. We conclude that PGE2 in late
      gestation ovine fetal plasma does not tonically stimulate fetal ACTH secretion.

PMID- 15866109
TI  - Establishment and characterization of a human first-trimester extravillous
      trophoblast cell line (TEV-1).
AB  - OBJECTIVE: Research into the biology of human trophoblast invasion has been
      hampered by a lack of in vitro models. The aim of this study was to establish and
      characterize a human extravillous trophoblast cell line from the first-trimester
      placenta. METHODS: Human papillomavirus type 16 (HPV16) E6/E7 genes were stably
      expressed in primary cultures of first-trimester placenta via a retroviral vector
      (pLXSN-E6/E7). Several clones were characterized for extravillous trophoblastic
      properties by reverse transcriptase polymerase chain reaction (RT-PCR), Western
      blotting, and immunocytochemistry. The activities of matrix metalloproteinase
      (MMP)-2 and MMP-9 were examined with gelatin zymography. One clone (TEV-1), which
      retains all the established criteria for extravillous trophoblasts, was used in
      microarray analysis with Stanford Human cDNA chip (41, 421 cDNA features) to
      examine the differential gene expression after treatment of transforming growth
      factor beta 1 (TGFbeta1). The responsive gene to TGFbeta1 treatment was confirmed
      by quantitative real-time PCR. RESULTS: The clonal TEV-1 has been passaged for
      more than 105 population doublings with no sign of senescence, the activation of
      telomerase at early passages, and a near-diploid karyotype. TEV-1 cells expressed
      cytokeratin 7, HLA-G (a histocompatibility antigen, class IB), and CD9 (the
      cluster of differentiation antigen 9), and secreted active MMP-2 and MMP-9.
      TGFbeta1 treatment altered the gene expression profile of TEV-1 cells with a
      marked up-regulation of insulin-like growth factor binding protein 3 (IGFBP3),
      which was confirmed by quantitative real-time PCR. In addition, the TEV-1 was
      nontumorigenic when injected into nude mice and unable to form colonies in soft
      agar. CONCLUSION: Phenotypic and biologic characteristics of TEV-1 were shown as
      the properties of extravillous trophoblasts; thus, the TEV-1 cell line may be
      used as a cell model in extravillous trophoblast studies.

PMID- 15866110
TI  - Inhibition of in vitro contractions of human myometrium by mibefradil, a T-type
      calcium channel blocker: support for a model using excitation-contraction
      coupling, and autocrine and paracrine signaling mechanisms.
AB  - OBJECTIVE: To investigate the importance of T-type calcium channels in human
      myometrial contractility and to refine a model of contractility. METHODS: We
      performed in vitro muscle bath experiments on human myometrial tissue strips
      while simultaneously monitoring bioelectrical activity with loose-contact
      electrodes. Tissue was obtained by myometrial biopsy from term pregnant women at
      the time of cesarean delivery and studied after 1 to 7 days in organ culture.
      Tissue strips were exposed to 5 nM oxytocin to obtain regular contractions.
      Tissue was then exposed to the T-type calcium channel blocker mibefradil (1
      microM), the L-type calcium channel blocker nifedipine (5 nM), or the
      cyclooxygenase (COX) inhibitor indomethacin (30 microM). All study drugs reduced
      the strength of contractions. Data were analyzed using a model composed of two
      phases of force production--an electrical phase (E), which encompassed the first
      3 seconds of each contraction, and a paracrine phase (P), which continued until
      the peak of the contraction. For each phase, the relative force reduction was
      calculated by the ratio of forces measured after and before drug exposure (RE and
      RP, respectively). For each drug, experiments were performed in at least
      triplicate. RESULTS: Myometrial contractions and bioelectrical signals were
      routinely observed following oxytocin exposure. Spike-like bioelectrical signals
      occurred only at the beginning of each contraction. Nifedipine and indomethacin
      slightly modulated the bioelectrical signals, but mibefradil appeared to block
      the spike component. Mibefradil caused a similar reduction of E and P (RE = 58 +/
      10%, RP = 62 +/- 22%). Nifedipine also reduced E and P, although P was reduced
      more than E (RE = 72 +/- 12%, RP = 38 +/- 8%, P = .006). Indomethacin yielded
      variable results, with some experiments showing similar RE and RP values, while
      other experiments showed RP > RE. CONCLUSION: Mibefradil inhibition of the
      bioelectrical signal and uterine contractile forces suggest that T-type calcium
      channels are important in the initiation of each contraction. Some results using
      indomethacin suggest that for a specific tissue or under some conditions,
      autocrine stimulation by prostaglandins may be important for recruitment of
      myocytes in the electrical phase. Stimulation by prostaglandins is likely
      important in the paracrine phase. Enhanced inhibition by nifedipine in the
      paracrine phase suggests the mechanism of action of nifedipine tocolytic effect
      is block of prostaglandin F2alpha (PGF2alpha) paracrine stimulation. Our initial
      model proposed at least two mechanisms (electrical and nonelectrical) for the
      recruitment of myocytes. Our modified model suggests that the electrical phase
      contains a prostaglandin autocrine mechanism in addition to excitation
      contraction coupling, and the mechanism in the nonelectrical phase is
      prostaglandin paracrine signaling.

PMID- 15866111
TI  - Progesterone isoforms and endometrial cancer.

PMID- 15866112
TI  - Strategies for fertility preservation in female and male cancer survivors.
AB  - Improved survival rates and quality of life following modern cancer treatment
      have resulted in a growing number of patients requesting maintenance of
      reproductive capacity, both before and after completion of treatment. Several
      established options are currently available. In men, sperm banking should be
      offered as soon as the diagnosis of any malignant disease is established,
      irrespective of the expected cryosurvival rate. In such cases, conception can be
      achieved with frozen-thawed spermatozoa following either intrauterine
      insemination (IUI) or intracytoplasmic sperm injection (ICSI). In women,
      depending on the type of cancer, the presence of an adequate ovarian reserve, and
      time to delay cancer treatment, in vitro fertilization (IVF) with embryo
      cryopreservation constitutes a valid alternative. On the other hand,
      cryopreservation of mature oocytes following IVF/ICSI offers some advantages, but
      it is still limited by its low success rate. Emerging and exciting techniques of
      germ cell/gonadal tissue cryopreservation (banking) followed by
      autotransplantation have been clinically explored, particularly in women. Novel
      cryotechnologies of ovarian and testicular tissue have proven efficacious and new
      transplantation strategies promise improved results. However, only one live birth
      following autotransplanted frozen-thawed ovarian tissue has been established and
      there are still no pregnancies reported from autotransplanted cryopreserved
      testicular tissue in the human. Efficiency and safety of these techniques needs
      to be demonstrated. Methods for gamete in vitro maturation also need further
      development. Gonadal tissue cryopreservation and transplantation should be
      considered experimental in humans for the present time until greater evidence
      regarding efficacy and safety is accrued.

PMID- 15866113
TI  - The effect of mild hypothermia on insulin-like growth factors after severe
      asphyxia in the preterm fetal sheep.
AB  - OBJECTIVES: Persistent reductions in insulin-like growth factor I (IGF-I) levels
      in the preterm infant are strongly associated with increased risk of retinopathy
      and other complications, and may result from exposure to severe hypoxia. The
      effects of a potential new treatment for hypoxic-ischemic encephalopathy,
      cerebral hypothermia, on the responses of the IGF axis to hypoxia are unknown.
      The aim of this study was to examine the effects of prenatal asphyxia and
      cerebral hypothermia on changes in IGF-I and -II, IGF-binding protein 1 (IGFBP
      1), and insulin levels. METHODS: Fetal sheep at 0.7 of gestation underwent either
      sham asphyxia and sham cooling (n = 7), asphyxia induced by 25 minutes of
      complete umbilical cord occlusion alone (n = 8), or asphyxia and head cooling (n
      = 8, extradural temperature 29.5 +/- 2.6C [vs 39.4 +/- 0.3C; P < .05]). Fetuses
      were studied for 3 days post-insult, during which time fetal blood samples were
      taken for endocrine measurements. RESULTS: There were no IGF axis changes during
      occlusion. Plasma IGF-I levels significantly decreased between 6 hours and 48
      hours after asphyxia and IGF-II levels by 10 hours, in both asphyxia groups.
      IGFBP-1 rose from 4 hours, reaching a peak at 10 hours and returning to control
      values by 48 hours in the normothermia group, and by 24 hours in the hypothermia
      group. Insulin levels decreased between 2 hours and 10 hours after asphyxia in
      both asphyxia groups, and subsequently normalized. CONCLUSIONS: This study
      demonstrates for the first time that transient asphyxia in the preterm sheep
      fetus is associated with a significant decrease in IGF-II as well as IGF-I during
      recovery, and that these responses are not altered by mild systemic hypothermia.

PMID- 15866114
TI  - The effects of chorioamnionitis and betamethasone on 11beta hydroxysteroid
      dehydrogenase types 1 and 2 and the glucocorticoid receptor in preterm human
      placenta.
AB  - OBJECTIVE: Preterm birth is one of the major problems faced in perinatal medicine
      and is often associated with underlying clinical infection. Treatment with
      maternal betamethasone has helped to improve neonatal morbidity and mortality. We
      hypothesized that betamethasone treatment and chorioamnionitis would alter the
      bioavailability of placental glucocorticoids through the regulation of the 11beta
      hydroxysteroid dehydrogenase (11beta HSD) isozymes and the glucocorticoid
      receptor (GR). METHODS: Placental samples were obtained from three groups of
      women who delivered prematurely: (1) those who delivered in the absence of
      infection, (2) those who received betamethasone treatment before delivering
      without infection, and (3) those who had pregnancies complicated with
      chorioamnionitis. Western blotting was used to determine 11beta HSD-1, 11beta HSD
      2, GRT, and GRalpha expression, and 11beta HSD-2 activity was determined in each
      group. JEG-3 cells were used to study the regulation of the 11beta HSD isozymes.
      RESULTS: In cases of chorioamnionitis where mothers had not been treated with
      betamethasone, placental 32-kd 11beta HSD-1 protein expression was increased. In
      cases of chorioamnionitis regardless of betamethasone treatment, placental 11beta
      HSD-2 expression and activity was decreased compared to controls. In these
      placental samples, the expression of GRT and GRalpha did not change
      significantly. In JEG-3 cells, 11beta HSD-1 32-kd expression was increased with
      interleukin (IL)-1beta and tumor necrosis factor alpha (TNF-alpha), while 11beta
      HSD-2 expression was unaffected. CONCLUSION: These data suggest that there could
      be an increased fetal exposure to maternal glucocorticoids in cases of
      chorioamnionitis as a result of changes in the expression and activity of the
      placental 11beta HSD isozymes.

PMID- 15866115
TI  - The measurement of dendritic cells in umbilical cord blood: a novel technique
      using small volumes of whole blood.
AB  - OBJECTIVE: To develop a technique that would permit the identification of
      dendritic cells (DC) in small volumes of preterm neonatal cord blood in order to
      investigate neonatal immune response in relation to infection and preterm labor.
      METHODS: We used three-color flow cytometry and a fixed quantity of fluorospheres
      to determine absolute cell numbers. Four red cell lysis techniques, sample
      dilution, time delay experiments, and a comparison with traditional Ficoll cell
      separation techniques were performed. Absolute numbers of DC recovered using each
      technique were calculated and compared. RESULTS: With increasing time delay,
      there was a statistically significant reduction in the numbers of leukocytes in
      adult blood. In contrast, there was a significant increase in leukocytes in
      umbilical cord blood. Sample dilution did not significantly affect the total
      number of leukocytes or DC. The use of the reagent Optilyse B (Immunotech,
      Oxford, UK) combined with an additional washing step produced the best
      discrimination of all populations based on light scatter properties. For the same
      blood sample, antibody labeling of whole blood resulted in a greater recovery of
      DC when compared to prior cell purification using a Ficoll density gradient.
      CONCLUSION: Using traditional Ficoll cell separation, cell manipulation requires
      large volumes of blood and leads to cell loss and alteration in phenotype. We
      have validated a novel method using small volumes of whole blood, diluted if
      necessary, and using red cell lysis to enable analysis of small volumes of
      preterm neonatal cord blood. This may permit further analysis of the contribution
      of the fetal immune response in the development of spontaneous preterm labor and
      preterm birth due to infection.

PMID- 15866116
TI  - Preeclampsia is associated with global cerebral hemodynamic changes.
AB  - OBJECTIVE: To compare blood flow-velocity parameters in the anterior and
      posterior cerebral arteries between normotensive and preeclamptic pregnant women.
      METHODS: Transcranial Doppler ultrasound was used to measure peak, end-diastolic,
      and mean velocities in the anterior cerebral artery (ACA) and posterior cerebral
      artery (PCA) of 22 normotensive and 12 preeclamptic women in the third trimester.
      All measurements were performed with the subject in the left lateral position.
      Blood pressure and heart rate were recorded with each Doppler measurement. The
      mean pulsatility index (PI), resistance index (RI), and cerebral perfusion
      pressure for each artery was averaged and compared. Statistical significance was
      set at P <.05. RESULTS: Preeclamptic women had higher cerebral perfusion pressure
      in both ACA and PCA (64.7 +/- 5.9 and 78.1 +/- 7.6 compared with 42.4 +/- 2.6 and
      54.1 +/- 4.1 mmHg, P <.05), lower PI (0.83 +/- 0.05 and 0.71 +/- 0.04 compared
      with 0.96 +/- 0.04 and 0.84 +/- 0.02, P <.05), and lower RI (0.55 +/- 0.02 and
      0.49 +/- 0.02 compared with 0.60 +/- 0.02 and 0.55 +/- 0.01, P <.05) than
      normotensive pregnant women. CONCLUSION: Preeclamptic patients have globally
      elevated cerebral perfusion pressure and lower resistance in the cerebral
      circulation than normotensive pregnant women.

PMID- 15866117
TI  - Differentiation of mouse embryonic stem cells into gonadotrope-like cells in
      vitro.
AB  - OBJECTIVE: This research was conducted to investigate the potential of mouse
      embryonic stem (ES) cells to differentiate in vitro into gonadotropes. METHODS:
      Undifferentiated ES cells were maintained on mitomycin C-inactivated fibroblasts
      in the presence of leukemia inhibitory factor (LIF). By a 5-day hanging drop
      culture devoid of them, ES cells were induced to form multidifferentiated
      structures called embryoid bodies (EBs). Reverse transcriptase-polymerase chain
      reaction (RT-PCR), Western blotting, and immunocytochemistry were used to analyze
      gene expression of gonadotrope markers in EBs at different time points during the
      culture. RESULTS: Homeo box gene expressed in ES cells (Hesx1), LIM homeobox
      protein 3 (Lhx3), paired like homeodomain factor 1 (Prop1), GATA binding protein
      2 (GATA2), follicle-stimulating hormone beta (FSHbeta), and luteinizing hormone
      beta (LHbeta) mRNAs were detected at day 6 EBs and maintained throughout the
      culture to day 56. FSHbeta and LHbeta proteins were expressed in EBs from day 6
      onward. Immunofluorescent labeling of FSHbeta and LHbeta showed that specific
      staining was restricted to the cytoplasm of some differentiated EB cells. With
      the prolongation of EB culture, the number of positive cells increased
      significantly. Both monohormonal and bihormonal cells were present, mainly in
      clusters within EBs and sparsely distributed among the outermost cells
      surrounding the EBs. CONCLUSION: These results indicate that mouse ES cells can
      give rise to mature gonadotrope-like cells in EBs. It also shows that EBs may
      serve as a novel model system to study the development and function of
      gonadotropes.

PMID- 15866118
TI  - Immunohistochemical expression of p53, MDM2, and p21Waf1 oncoproteins in
      endometriomas but not adenomyosis.
AB  - OBJECTIVE: p53, MDM2, and p21Waf1 are oncoproteins that regulate the cell cycle.
      The purpose of this study was to examine the distribution of p53, MDM2, and
      p21Waf1 oncoprotein expression in endometriomas and in adenomyosis. METHODS:
      Tissue samples from 25 women with pathologically confirmed endometriomas and 31
      women with pathologically confirmed adenomyosis were analyzed. Expression of p53,
      MDM2, and p21Waf1 oncoproteins was assessed by immunohistochemical nuclear
      staining. RESULTS: p53, MDM2, and p21Waf1 expression were detected in 20%, 60%,
      and 80% of endometrioma tissue samples, respectively. All endometrioma tissue
      samples expressing p53 also tested positive for both MDM2 and p21Waf1. MDM2
      expression was significantly higher in the proliferative than in the secretory
      phase of the cycle. In contrast, all 31 adenomyosis tissue samples were negative
      for p53, MDM2, and p21Waf1 expression. CONCLUSION: The expression of p53, MDM2,
      and p21Waf1 suggests a role for these oncoproteins in the regulation of
      endometrioma cell growth, but not in adenomyosis.

PMID- 15866119
TI  - Association study of endometriosis and intercellular adhesion molecule-1 (ICAM-1)
      gene polymorphisms in a Japanese population.
AB  - OBJECTIVE: Endometriosis is an immune-related, chronic inflammatory disease with
      polygenic predisposition. Cell adhesion molecules are expressed in endometriotic
      lesions, and in cells and tissues that are involved in the development and
      progression of the disease. In this study, we investigated the possible
      association between endometriosis and the G241R and K469E polymorphisms in the
      intercellular adhesion molecule-1 (ICAM-1) gene in a Japanese population.
      METHODS: We compared the distribution of the G241R and K469E polymorphisms in the
      ICAM-1 gene in 126 endometriosis patients and 172 controls using polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in a
      Japanese population. RESULTS: There were no significant differences between the
      cases and controls in the allele frequencies or genotype distributions of either
      the G241R or K469E polymorphisms in the ICAM-1 gene. The endometriosis patients
      were divided into a subgroup of women with severe disease only. However, no
      significant differences were observed in the allele frequencies and genotype
      distributions of the ICAM-1 K469E polymorphisms between this subgroup and the
      controls. In contrast, only one in 169 controls was heterozygous (G/A genotype),
      and the A allele in the G241R polymorphism was not found in any of the 126
      endometriosis patients. CONCLUSION: Our findings suggest that the G241R and K469E
      polymorphisms in the ICAM-1 gene are unlikely to be associated with an increased
      risk of endometriosis in the Japanese population.

PMID- 15866120
TI  - Vitamin D binding protein in endometriosis.
AB  - OBJECTIVE: Two-dimensional gel electrophoresis is a powerful method for
      identifying post-translationally modified molecules in biological fluids. We
      examined the presence and expression of vitamin D binding protein (DBP) in the
      peritoneal fluid (PF) and plasma (PL) of women with endometriosis. METHODS: PL
      and PF samples were obtained from 36 women with untreated mild endometriosis
      (revised classification of the American Fertility Society [rAFS] stage I-II), 52
      women with untreated severe endometriosis (rAFS stage III-IV), 17 women with
      endometriosis treated with the oral contraceptive (OC), and 40 controls
      (infertility, n = 23; tubal sterilization, n = 12; pelvic pain, n = 5). PF and PL
      samples were analyzed by quantitative, high-resolution 2-dimensional gel
      electrophoresis. RESULTS: The expression of one DBP isoform (DBPE) in the PF of
      patients with untreated endometriosis was significantly lower than in the control
      group (P <.05). The levels of PF DBPE in patients with endometriosis using OC
      were significantly higher than in women with untreated endometriosis (P <.05). No
      significant difference was observed in PL DBPE expression between women with and
      without endometriosis, while it was significantly increased in patients with
      endometriosis using OC (P <.05). DBP expression was not correlated with the stage
      of endometriosis (rAFS classification) or the phase of the menstrual cycle.
      CONCLUSION: The decreased level of DBPE in the PF but not in PL of women with
      untreated endometriosis suggests that this molecule may be relevant in the
      pathogenesis of this disease.

PMID- 15866121
TI  - Differences in invasive capacity of endometrial cancer cell lines expressing
      different progesterone receptor isotypes: possible involvement of cadherins.
AB  - OBJECTIVE: Loss of expression of progesterone receptors (PR) in endometrial
      cancer is related to a more invasive and metastatic phenotype. In this study we
      aim to investigate whether selective loss of PRA or PRB affects the invasive
      capacity of endometrial cancer cells. METHODS: cDNA microarrays were performed to
      compare gene expression profiles of a set of endometrial cancer sub-cell lines
      expressing PRA and/or PRB. In vitro invasion assays were performed to assess
      whether differences in gene expression between the lines were reflected by their
      invasive behavior. RESULTS: It was observed that cell lines that express only PRA
      express higher levels of cadherins, and show a lower level of invasion compared
      to cell lines that express PRB. When cadherin function was inhibited in
      exclusively PRA-expressing cell lines, an increase of in vitro invasion was
      observed. In support of these findings, it was observed that in higher grade and
      more invasive endometrial cancer, expression of E-cadherin decreased.
      CONCLUSIONS: These results indicate that relative loss of PRA during progression
      of endometrial cancer can have a negative impact on cadherin expression, which
      may lead to development of a more metastatic phenotype.

PMID- 15866122
TI  - Progesterone-induced inhibition of growth and differential regulation of gene
      expression in PRA- and/or PRB-expressing endometrial cancer cell lines.
AB  - OBJECTIVE: Progesterone plays an important role in controlling proliferation and
      differentiation of the human endometrium. Because there are two progesterone
      receptor isoforms (PRA and PRB), it was important to generate tools to be able to
      study the role of these two progesterone receptors separately. METHODS: Using
      stable transfection techniques, both human progesterone receptor isoforms (hPRA
      and hPRB) were reintroduced into a hPR-negative subclone of the well
      differentiated endometrial cancer cell line Ishikawa. Several Ishikawa subcell
      lines were constructed, each expressing different levels of hPRA, hPRB, or hPRA
      and hPRB, respectively. RESULTS: These Ishikawa subcell lines showed a marked
      progesterone-induced growth inhibition with induction of apoptosis after long
      term culture in the presence of hormone. Upon measuring gene regulation, a clear
      difference in regulation of expression of the selected genes by progesterone
      treatment was observed between the PRA-, PRB-, or PRA/B-expressing cell lines.
      Integrin beta4 (ITGB4) was only regulated in PRA-expressing cells; amphiregulin
      was highly regulated in PRB-expressing cells; insulin-like growth factor binding
      protein 3 (IGFBP3) was only regulated in PRB- and PRA/B-expressing cells; and
      metallothionein 1L (MT1L) was highly regulated in PRA/B-expressing cells.
      Interestingly, based on literature data, these genes can be implicated in
      induction of apoptosis, but are modulated here in such a way that suggests
      induction of resistance against apoptosis. CONCLUSION: Reintroduction of PRs into
      Ishikawa cells rescued progesterone responsiveness in these cells. Furthermore,
      using these human endometrial cancer subcell lines, clear and distinct functional
      differences between the PR isoforms were observed.

PMID- 15866123
TI  - Memory performance in late pregnancy and erythrocyte indices.
AB  - OBJECTIVE: A previous study in elderly people observed an association between
      chronologically younger erythrocyte population and memory impairment. The aim of
      this study was to assess whether a similar shift in erythrocyte population in
      pregnant women in late pregnancy is associated with changes in memory performance
      in healthy pregnant women. METHODS: Thirty healthy pregnant women were included
      in a prospective cross-sectional study. Explicit memory and autobiographic memory
      tests were performed in the late third trimester and 4 months postpartum. Mean
      corpuscular volume (MCV) was considered the primary predictor variable. RESULTS:
      The mean explicit memory recall scores were significantly higher at post-delivery
      compared to pre-delivery: 8.3 +/- 1.7 and 7.4 +/- 1.4, respectively (P = .015).
      The difference in mean autobiographic memory test score pre- and post-delivery
      did not reach statistical significance. A positive correlation between post
      delivery explicit memory recall scores and the difference between pre- and post
      delivery MCV was detected (r = 0.458, P = .01). The correlation between delta MCV
      and delta explicit memory recall scores was r = 0.2, P =.311. Pre-delivery
      autobiographic memory test scores were positively correlated with MCV (r = 0.50,
      P = .006), mean corpuscular hemoglobin (r = 0.57, P = .001), and mean corpuscular
      hemoglobin concentration (r = 0.46, P = .013). CONCLUSION: The change in
      erythrocyte population that is present in late pregnancy predicted explicit
      memory performance after delivery, when it was improved. The younger erythrocyte
      population that exists in late pregnancy is associated with a better
      autobiographic memory.

PMID- 15866124
TI  - Autism and ADHD: common disorders, elusive explanations.

PMID- 15866125
TI  - C-mode real-time tomographic reflection for a matrix array ultrasound sonic
      flashlight.
AB  - RATIONALE AND OBJECTIVES: Real-time tomographic reflection (RTTR) permits in situ
      visualization of tomographic images so that natural hand-eye coordination can be
      used directly during invasive procedures. The method uses a half-silvered mirror
      to merge the visual outer surface of the patient with a simultaneous scan of the
      patient's interior without requiring a head-mounted display or tracking. A
      viewpoint-independent virtual image is reflected precisely into its actual
      location. When applied to ultrasound, we call the resulting RTTR device the sonic
      flashlight. We previously implemented the sonic flashlight using conventional two
      dimensional ultrasound scanners that produce B-mode slices. Real-time three
      dimensional (RT3D) ultrasound scanners recently have been developed that permit
      RTTR to be applied to slices with other orientations, including C-mode (parallel
      to the face of the transducer). Such slice orientation may offer advantages for
      image-guided intervention. MATERIALS AND METHODS: Using a prototype scanner
      developed at Duke University (Durham, NC) with a matrix array that electronically
      steers an ultrasound beam at high speed in 3D, we implemented a sonic flashlight
      capable of displaying C-mode images in situ in real time. RESULTS: We present the
      first images from the C-mode sonic flashlight, showing bones in the hand and the
      cardiac ventricles. CONCLUSION: The extension of RTTR to matrix array RT3D
      ultrasound offers the ability to visualize in situ slices other than the
      conventional B-mode slice, including C-mode slices parallel to the face of the
      transducer. This orientation may provide a broader target, facilitating certain
      interventional procedures. Future work is discussed, including display of slices
      with arbitrary orientation and use of a holographic optical element instead of a
      mirror.

PMID- 15866126
TI  - Using computer vision to help the determination of the gestational age of
      newborns.
AB  - RATIONALE AND OBJECTIVES: This report presents a computational approach to help
      the gestational age determination of newborns. Gestational age knowledge is
      fundamental to guide postnatal treatment and increase survival chances of
      newborns. However, current methods are invasive and do not generate precise
      results, mainly because they were developed based on nonpremature populations.
      MATERIALS AND METHODS: We developed an original and noninvasive method to help
      determination of gestational age based on information supplied by plantar surface
      images. These images present many details and patterns, but, to date, have not
      received attention from the image-processing community. We provide a
      computational tool with suitable facilities to allow the image analysis, either
      automatically or user driven. This image-processing tool is presented here.
      RESULTS: The image-processing tool was developed on a user-driven basis. However,
      as a quantitative experiment, 186 images were processed without user intervention
      to observe tool behavior in performing different tasks. Although preliminary,
      experimental results confirm the relationship between plantar surface features
      and gestational age. CONCLUSION: A prototype of the FootScanAge System is being
      used and evaluated by experts in neonatology. By means of digital processing of
      plantar surface images, some characteristics may be shown. Some hypotheses
      regarding the method have already been confirmed. Also, we show that some well
      known image-processing techniques, if appropriately adapted, lead to suitable
      results when applied to plantar surface images.

PMID- 15866127
TI  - From anatomic standardization analysis of perfusion SPECT data to perfusion
      pattern modeling: evidence of functional networks in healthy subjects and
      temporal lobe epilepsy patients.
AB  - RATIONALE AND OBJECTIVES: In the general context of perfusion pattern modeling
      from single-photon emission computed tomographic (SPECT) data, the purpose of
      this study is to characterize interindividual functional variability and
      functional connectivity between anatomic structures in a set of SPECT data
      acquired from a homogeneous population of subjects. MATERIALS AND METHODS: From
      volume of interest (VOI)-perfusion measurements performed on anatomically
      standardized SPECT data, we proposed to use correspondence analysis (CA) and
      hierarchical clustering (HC) to explore the structure of statistical dependencies
      among these measurements. The method was applied to study the perfusion pattern
      in two populations of subjects; namely, SPECT data from 27 healthy subjects and
      ictal SPECT data from 10 patients with mesio-temporal lobe epilepsy (MTLE).
      RESULTS: For healthy subjects, anatomic structures showing statistically
      dependent perfusion patterns were classified into four groups; namely,
      temporomesial structures, internal structures, posterior structures, and
      remaining cortex. For patients with MTLE, they were classified as temporomesial
      structures, surrounding temporal structures, internal structures, and remaining
      cortex. Anatomic structures of each group showed similar perfusion behavior so
      that they may be functionally connected and may belong to the same network. Our
      main result is that the temporal pole and lenticular nucleus seemed to be highly
      relevant to characterize ictal perfusion in patients with MTLE. This exploratory
      analysis suggests that a network involving temporal structures, lenticular
      nucleus, brainstem, and cerebellum seems to be involved during MTLE seizures.
      CONCLUSION: CA followed by HC is a promising approach to explore brain perfusion
      patterns from SPECT VOI measurements.

PMID- 15866128
TI  - Comparative study of cerebral white matter in autism and attention
      deficit/hyperactivity disorder by means of magnetic resonance spectroscopy.
AB  - RATIONALE AND OBJECTIVES: Autism and attention-deficit/hyperactivity disorder
      (ADHD) are neurodevelopmental disorders whose pathophysiology is mostly unknown.
      As far as the symptoms are different and, in some aspects, opposed, we
      hypothesize that there must be biochemical differences in the brain of the
      afflicted children. The aim of the study is to analyze comparatively the
      metabolite concentration of the cerebral white matter in autism, in ADHD, and in
      a control group of healthy children to test the hypothesis that N-acetyl
      aspartate (NAA) is decreased in autism and increased in ADHD. PATIENTS AND
      METHODS: We included 21 autistic children according to DSM-IV criteria, 8
      children with ADHD meeting the respective criteria of DSM-IV, and 12 healthy
      controls of similar age. Single-voxel proton magnetic resonance spectroscopy was
      performed on all of them with an echo time of 30 milliseconds and a repetition
      time of 2500 milliseconds. The voxel was placed in the left centrum semiovale.
      Metabolite ratios relative to creatine were reported for NAA, choline, and
      myoinositol. RESULTS: Although we did not observe differences between autistic
      children and controls, we found a mean higher concentration of NAA in the left
      centrum semiovale of ADHD children (2.2; SD, 0.21) than that found in autistic
      children (1.88; SD, 0.18) and controls (1.91; SD, 0.01), which was significant (P
      = .01 in parametric and in nonparametric test). CONCLUSION: We conclude that
      white matter of autistic children does not present alterations on MRS. We
      hypothesize that the higher concentration of NAA in the white matter of ADHD
      points to mitochondrial hypermetabolism. This may constitute a new substrate in
      the pathophysiology and merits further research.

PMID- 15866129
TI  - Computer-aided diagnosis of the solitary pulmonary nodule.
AB  - RATIONALE AND OBJECTIVES: We sought to investigate the utility of a computer
      aided diagnosis in the task of differentiating malignant nodules from benign
      nodules based on single thin-section computed tomography image data. MATERIALS
      AND METHODS: Eighty-one thin-section computed tomography data sets of solitary
      pulmonary nodules with proven diagnoses (48 malignant and 33 benign) were
      contoured manually on a single representative slice by a thoracic radiologist
      (>10 years of experience). Two separate contours were created for each nodule,
      one including only the solid portion of the nodule and one including any ground
      glass components. For each contour 75 features were calculated that measured the
      attenuation, shape, and texture of the nodule. These features were than input
      into a feature selection step and four different classifiers to determine if the
      diagnosis could be predicted from the feature vector. Training and testing was
      conducted in a resubstitution and leave-one-out fashion and performance was
      evaluated using ROC techniques. RESULTS: In a leave-one-out testing methodology
      the classifiers resulted with areas under the ROC curve (A(Z)) that ranged from
      0.68 to 0.92. When evaluating with resubstitution the A(Z) ranged from 0.93 to
      1.00. CONCLUSION: Computer-aided diagnosis has the potential to assist
      radiologists in the task of differentiating solitary pulmonary nodules and in the
      management of these patients.

PMID- 15866130
TI  - Optimal contrast agents for vascular imaging on computed tomography: iodixanol
      versus iohexol.
AB  - RATIONALE AND OBJECTIVES: Dimeric nonionic iodinated contrast has a lower
      osmolality than monomeric nonionic iodinated contrast but is available at lower
      iodine concentrations. Less dilution of intravascular fluid by influx from the
      extravascular space is proposed to occur with decreasing osmolality. The purpose
      of this study was to determine if a dimeric nonionic iso-osmolar contrast agent
      (iodixanol) gives equal vascular enhancement compared with a monomeric nonionic
      hyperosmolar contrast agent (iohexol). MATERIALS AND METHODS: A dynamic single
      level computed tomography (CT) scan was performed of the abdominal aorta of 12
      sedated rabbits using a four-row multidetector CT scanner following injection of
      1.5 mL contrast/kg body weight at 2 mL/sec. The rabbits were injected with the
      dimeric contrast agent iodixanol (Visipaque 320; Amersham Health) or the
      monomeric contrast agent iohexol (Omnipaque 350; Amersham Health). The order of
      the type of contrast media injected was randomized for each rabbit, and the
      interval between injections was 2 weeks. Using the 2.5-mm detectors, four
      contiguous 3-mm contrast-enhanced scans were obtained at a single level every 5
      seconds for 120 seconds (total of 24 scans) with a kVp of 120, mA.s of 110, field
      of view of 106 mm, and soft tissue reconstruction algorithm. A single level was
      chosen to measure the attenuation of the abdominal aorta at 5-second intervals.
      The mean attenuation and standard deviation values were recorded for the whole
      aorta, for the central half of the vessel, and for the peripheral half of the
      vessel. A log-log transformation of the data was performed and regression
      analysis was done on the outcomes of interest (e.g., mean, standard deviation) on
      time for each region. RESULTS: There was no statistically significant difference
      in mean attenuation for the whole aorta for iodixanol and iohexol (P = .918) even
      though the iodine content was 9.3% less with the dimeric iodixanol. The time
      attenuation curve of iodixanol paralleled that of iohexol for all time points.
      The mean attenuation values of the central half of the aorta (P = .354) and
      peripheral half of the aorta (P = .758) were also not statistically different for
      the two contrast agents. CONCLUSION: The vascular attenuation provided by a 9.3%
      lower iodine concentration of iso-osmolar iodixanol is equal to that given by
      hyperosmolar iohexol. This suggests that there is less intravascular dilution of
      iso-osmolar contrast. The enhancement across the cross section of the vessel is
      also similar for both contrast agents. This suggests the vascular studies with
      iodixanol and iohexol are of equal quality even when a lower dose of iodine is
      given with iodixanol. It is relevant for patients with borderline or diminished
      renal function in whom less volume of contrast may be administered.

PMID- 15866131
TI  - The effects of gray scale image processing on digital mammography interpretation
      performance.
AB  - RATIONALE AND OBJECTIVES: To determine the effects of three image-processing
      algorithms on diagnostic accuracy of digital mammography in comparison with
      conventional screen-film mammography. MATERIALS AND METHODS: A total of 201 cases
      consisting of nonprocessed soft copy versions of the digital mammograms acquired
      from GE, Fischer, and Trex digital mammography systems (1997-1999) and
      conventional screen-film mammograms of the same patients were interpreted by nine
      radiologists. The raw digital data were processed with each of three different
      image-processing algorithms creating three presentations-manufacturer's default
      (applied and laser printed to film by each of the manufacturers), MUSICA, and
      PLAHE-were presented in soft copy display. There were three radiologists per
      presentation. RESULTS: Area under the receiver operating characteristic curve for
      GE digital mass cases was worse than screen-film for all digital presentations.
      The area under the receiver operating characteristic for Trex digital mass cases
      was better, but only with images processed with the manufacturer's default
      algorithm. Sensitivity for GE digital mass cases was worse than screen film for
      all digital presentations. Specificity for Fischer digital calcifications cases
      was worse than screen film for images processed in default and PLAHE algorithms.
      Specificity for Trex digital calcifications cases was worse than screen film for
      images processed with MUSICA. CONCLUSION: Specific image-processing algorithms
      may be necessary for optimal presentation for interpretation based on machine and
      lesion type.

PMID- 15866132
TI  - Bronchomalacia in sarcoidosis: evaluation on volumetric expiratory high
      resolution CT of the lung.
AB  - RATIONALE AND OBJECTIVES: The aim of this study is to investigate the frequency
      of bronchomalacia associated with sarcoidosis and compare the extent of air
      trapping in patients with sarcoidosis with and without bronchomalacia. MATERIALS
      AND METHODS: Eighteen consecutive patients (6 men, 12 women; age, 29-64 years;
      mean age, 47 years) with pathologically proven sarcoidosis who underwent clinical
      volumetric expiratory high-resolution computed tomography were studied. On
      contiguous end-expiratory images, the presence and severity of bronchomalacia and
      extent of air trapping were evaluated. The extent of air trapping was compared
      between patients with sarcoidosis with and without bronchomalacia. RESULTS:
      Bronchomalacia was noted in 11 of 18 patients (61%) with sarcoidosis (grade 1
      [mild], n = 6; grade 2 [moderate], n = 4; and grade 3 [severe], n = 1). Air
      trapping was observed in 17 of 18 patients (94%; grade 1 [1%-25%], n = 8; grade 2
      [26%-50%], n = 9). The extent of air trapping in patients with bronchomalacia was
      significantly greater than that in patients without bronchomalacia (P = .027, chi
      squared test). CONCLUSION: Bronchomalacia frequently was associated with
      sarcoidosis, and the extent of air trapping was significantly greater in patients
      with sarcoidosis with bronchomalacia compared with those without bronchomalacia.

PMID- 15866133
TI  - Comparison of artifacts on coronal reformation and axial CT pulmonary angiography
      images using single-detector and 4- and 8-detector multidetector-row helical CT
      scanners.
AB  - RATIONALE AND OBJECTIVES: The aim of this study is to compare the degree of stair
      step artifact on coronal reformation computed tomographic (CT) pulmonary
      angiography images obtained using single-detector helical CT (SDCT), four
      detector (4-MDCT), and eight-detector multidetector-row CT (8-MDCT) and compare
      the degree of motion artifact on the corresponding axial CT images. MATERIALS AND
      METHODS: Three groups of consecutive patients imaged by means of CT angiography
      for suspected pulmonary embolus were retrospectively identified by using CT
      records at our institution: (1) group A (n = 38), SDCT; (2) group B (n = 36), 4
      MDCT; and (3) group C (n = 74), 8-MDCT. For each case, coronal multiplanar volume
      reformation maximal intensity projection images were created by using a standard
      technique. All images were reviewed in a randomized fashion by two thoracic
      radiologists who were blinded to the type of CT scanner. Stair-step artifact of
      pulmonary arteries on coronal reformation images was graded by consensus
      agreement using a four-point scale (0 = no artifact to 3 = severe artifact).
      Axial images were assessed for six parameters of motion artifact. The sum of
      these grades resulted in a total motion score, with a potential range of 0 (no
      motion) to 12 (severe motion). Statistical analysis was performed using the Mann
      Whitney test. RESULTS: Stair-step artifacts were significantly higher for SDCT
      (mean, 2.9; median, 3) compared with 4-MDCT (mean, 2.2; median, 2; P < .0001) and
      8-MDCT (mean, 1.5; median, 1; P < .0001). Total motion scores were significantly
      higher for SDCT (mean, 9.3) compared with 4-MDCT (mean, 8.4; P = .03) and 8-MDCT
      (mean, 6.8; P < .0001). CONCLUSION: Stair-step artifacts are significantly higher
      with SDCT compared with MDCT. For MDCT, eight-detector scanners produce images
      with significantly less artifact than four-detector scanners.

PMID- 15866134
TI  - Automated volumetry at CT colonography: a phantom study.
AB  - RATIONALE AND OBJECTIVES: To assess the performance of a computer-aided detection
      (CAD) algorithm for measuring polyp-like structures on CT colonography (CTC)
      images of a phantom. MATERIALS AND METHODS: We constructed a Plexiglas phantom to
      which we affixed a series of idealized Plexiglas polyp-like objects, including
      spheres and hemispheres. We imaged the phantom in a four-channel detector CT
      scanner at a 1.3 mm slice thickness with a reconstruction interval of 0.6 mm,
      using combinations of 100 mAs, 30 mAs, horizontal and vertical orientation. For
      each set of CT images, the interior surface of the phantom was segmented. The CAD
      algorithm was applied to the resulting surface to identify the polypoid regions
      of interest and to calculate their volume and maximum linear dimension.
      Calculated values were then compared with actual values to yield percent error in
      each measurement. RESULTS: The mean error in volume for the subgroups of spheres
      and hemispheres was 3% and 5% respectively. Mean error in linear dimension was
      approximately 2% for both shape subgroups. All CAD-calculated values were closely
      correlated with their respective actual values. Parameter selection did not
      significantly affect the accuracy of the calculated measurements. CONCLUSIONS:
      Our CAD software accurately measured the greatest linear dimension and the volume
      of each of the polyp-like structures in our phantom. Results were largely
      independent of phantom orientation and the CT exposure factors.

PMID- 15866135
TI  - Multi-detector row CT: is prospective electrocardiographic triggering improving
      the detection of small pulmonary tumors?
AB  - RATIONALE AND OBJECTIVES: To compare prospectively ECG-triggered multi-detector
      row computed tomography (ECG-MDR-CT) and multi-detector row computed tomography
      (MDR-CT) without triggering for the detection of pulmonary tumors. MATERIALS AND
      METHODS: 100 patients with proven or suspected tumors were referred for CT of the
      lung for staging of lung metastases. First, a non-enhanced scan was performed
      using prospective ECG-triggering on a four-row multidetector helical CT scanner,
      followed by a contrast-enhanced scan without triggering. The diagnostic
      assessibility in detecting intrapulmonary nodules and mediastinal structures was
      graded using a 5-point scale (rated 1 = bad to 5 = very good image quality).
      RESULTS: ECG-MDR-CT images detected a total of 26% more pulmonary nodules than
      MDR-CT. For tumors <5 mm, the detection rate was 62% higher using ECG-triggered
      scans (P = .024). Subjective assessment found median demarcation ratings for all
      pulmonary findings of 4 (ECG-MDR-CT) versus 3 (MDR-CT). Mediastinal structures
      were delineated better using ECG triggering. The median ranking for demarcation
      of pulmonary findings <10 mm was 4 on ECG-MDR-CT and 3 on MDR-CT, respectively.
      For vessels and the left bronchus, the median of demarcation was 4 on triggered
      images and 2 on MDR-CT, respectively. The median values referring to the
      demarcation of mediastinal structures were not significantly different between
      ECG-MDR-CT and MDR-CT. CONCLUSION: Our data indicate the superiority of
      prospectively triggered ECG-MDR-CT over MDR-CT for the diagnosis of small
      pulmonary tumors using a 4-row multidetector CT.

PMID- 15866136
TI  - Evidence and diagnostic reporting in the IHE context.
AB  - Capturing clinical observations and findings during the diagnostic imaging
      process is increasingly becoming a critical step in diagnostic reporting.
      Standards developers-notably HL7 and DICOM-are making significant progress toward
      standards that enable exchanging clinical observations and findings among the
      various information systems of the healthcare enterprise. DICOM-like the HL7
      Clinical Document Architecture (CDA) -uses templates and constrained, coded
      vocabulary (SNOMED, LOINC, etc.). Such a representation facilitates automated
      software recognition of findings and observations, intrapatient comparison,
      correlation to norms, and outcomes research. The scope of DICOM Structured
      Reporting (SR) includes many findings that products routinely create in digital
      form (measurements, computed estimates, etc.). In the Integrating the Healthcare
      Enterprise (IHE) framework, two Integration Profiles are defined for clinical
      data capture and diagnostic reporting: Evidence Document, and Simple Image and
      Numeric Report. This report describes these two DICOM SR-based integration
      profiles in the diagnostic reporting process.

PMID- 15866137
TI  - Rapid volumetric MRI using parallel imaging with order-of-magnitude accelerations
      and a 32-element RF coil array: feasibility and implications.
AB  - RATIONALE AND OBJECTIVES: Many clinical applications of Magnetic Resonance
      Imaging are constrained by basic limits on imaging speed. Parallel MRI relaxes
      these limits by using the sensitivity patterns of arrays of radiofrequency
      receiver coils to encode spatial information in a manner complementary to
      traditional encoding with magnetic field gradients. Until now, parallel MRI has
      been used to achieve modest improvements in imaging speed; order-of-magnitude
      improvements have been elusive given fundamental losses in signal-to-noise ratio.
      The goal of this work was to demonstrate that, with appropriate hardware and
      careful SNR management, rapid volumetric imaging at high accelerations is in fact
      feasible. MATERIALS AND METHODS: Contrast-enhanced MRI with an axial 3D spoiled
      gradient echo imaging sequence was performed in healthy adult subjects using a 32
      element RF coil array and a prototype 32-channel MR imaging system. Large imaging
      volumes were prescribed, in place of traditional limited slabs targeted only to
      suspect regions. RESULTS: As much as 16-fold net accelerations of imaging were
      achieved repeatably using this approach. The use of large 3D volumes allowed
      comprehensive anatomical coverage at clinically useful spatial and/or temporal
      resolution. The need for careful, time-consuming, and subject-specific scan
      prescription was also eliminated. CONCLUSION: The highly parallel imaging
      approach presented here allows previously inaccessible volumetric coverage for
      time-sensitive MRI examinations such as contrast-enhanced MRA, and simultaneously
      provides a substantially simplified imaging paradigm. The resulting capability
      for rapid volumetric imaging promises to combine the strengths of MRI with some
      of the advantages of alternative imaging modalities such as multidetector CT.

PMID- 15866138
TI  - Fat quantification using three-point dixon technique: in vitro validation.
AB  - RATIONALE AND OBJECTIVES: To test the repeatability, reproducibility and accuracy
      of the three-point Dixon (3PD) sequence for estimating true fat volume ratios
      using a fat/water phantom. MATERIALS AND METHODS: A phantom, constructed from
      test tubes of varying fat content, was imaged using the 3PD sequence on a 1.5T
      MRI scanner by two operators four times each. Fat volume ratios were calculated
      from these images and compared with true fat volumes. RESULTS: Measures of fat
      volume ratios calculated from the 3PD MR images correlated strongly with values
      for true fat volumes (r = 0.96). CONCLUSION: The 3PD technique was found to be
      highly reproducible and accurate, and may be useful for in vivo quantification of
      fat in lean tissues, such as the liver, pancreas or skeletal muscle.

PMID- 15866139
TI  - Usefulness of diffusion/perfusion-weighted MRI in rat gliomas: correlation with
      histopathology.
AB  - RATIONALE AND OBJECTIVES: Diffusion/perfusion-weighted MRI (DWI/PWI) can provide
      additional useful information in the diagnosis of patients with brain gliomas in
      a noninvasive fashion. However, the exact role of these new techniques is still
      undergoing evaluation. Our hypothesis was that DWI and PWI could be useful for
      assessment of growth and vascularity of implanted C6 rat gliomas. MATERIALS AND
      METHODS: Thirty-six rats were implanted with C6 glioma cells intracerebrally.
      Between 1 and 4 weeks after implantation, 8-10 rats were imaged on a clinical,
      1.5-T whole-body magnetic resonance system with T(1)-weighted imaging (T(1)WI),
      T(2)-weighted imaging, DWI, PWI, and postcontrast T(1)WI at each weekly time
      point. All tumors were examined histologically; tumor cellularity and
      microvascular density were counted. RESULTS: On DWIs, statistical differences of
      apparent diffusion coefficient values for both the tumoral core and peritumoral
      region were present comparing tumors of 3-4 weeks' growth with tumors of 1-2
      weeks' growth. Apparent diffusion coefficient value of tumoral core was
      negatively correlated with tumor cellularity (r = -0.682, P < .01). Statistical
      difference of maximal regional cerebral blood volume of tumoral core was present
      comparing 2-4 weeks with both 1 week after implantation and contralateral white
      matter (P < .01). Native vessel dilation in regions of normal brain at the
      periphery of the tumors at 1 week after implantation was observed. Correlation
      between maximal regional cerebral blood volume of tumor core and microvascular
      density was present (r = 0.716, P < .01). CONCLUSION: DWI and PWI has potential
      to characterize C6 gliomas in rats, which is a promising model similar to human
      gliomas.

PMID- 15866140
TI  - Preliminary experience with contrast-enhanced MR angiography in patients with end
      stage renal failure.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate our
      preliminary experience with routine contrast-enhanced magnetic resonance
      angiography (CE-MRA) of the lower limb arteries in patients with end-stage renal
      failure. MATERIALS AND METHODS: A retrospective analysis was performed on
      clinical, physiological, and imaging data for 104 patients with end-stage renal
      failure. Patients were considered to be in end-stage renal failure if they were
      on renal replacement therapy (peritoneal or hemodialysis) or were being evaluated
      as part of a pretransplant workup. CE-MRA was carried out on a 1.5-T scanner
      using a single-injection, three-station moving table technique. RESULTS: Eleven
      percent of asymptomatic patients with normal ankle/brachial pressure indexes
      (ABPI) were found to have severe arterial disease on CE-MRA, and in 30% of
      asymptomatic patients with abnormal ABPI, CE-MRA showed mild or no disease.
      Moreover two of three symptomatic patients with normal ABPI were shown to have
      severe disease. Two patients on peritoneal dialysis had to be switched to
      hemodialysis. No other adverse events were revealed. CONCLUSION: CE-MRA is a
      useful adjunct to clinical and physiological examination for the evaluation of
      the lower limb arteries in a group of patients who have a higher-than-average
      incidence of peripheral vascular disease, yet have previously been severely
      restricted from traditional angiography because of contrast-medium-induced
      nephrotoxicity.

PMID- 15866141
TI  - Radiology residents' on-call interpretation of chest radiographs for pneumonia.
AB  - RATIONALE AND OBJECTIVES: This study is designed to assess the performance of
      radiology residents in interpreting emergency department chest radiographs for
      pneumonia and to characterize chest radiographic findings in patients for which
      interpretation was amended by an attending radiologist. MATERIALS AND METHODS: We
      retrospectively reviewed all amended reports for chest radiographs performed on
      emergency department patients July 2002-June 2003. Reports preliminarily
      interpreted by residents and amended by a board-certified staff radiologist for
      the presence or absence of pneumonia were identified. A panel of three
      experienced radiologists, blinded to reports, jointly reviewed each chest
      radiograph. If the panel diagnosed pneumonia, the chest radiograph was evaluated
      for the projection that best showed the pneumonia, its size and location, and the
      presence or absence of the following features: increased opacity, air
      bronchograms, loss of vascular markings, silhouette sign, and linear opacities.
      The resident's post-graduate year (PGY) training level was noted. RESULTS: One
      percent (134/12,600 reports) of chest radiographic reports were amended for the
      presence or absence of pneumonia. One hundred chest radiographs were available
      and comprised the series. There were 56 females and 44 males with a mean age of
      45 years (range, 1-99 years). The staff radiologist diagnosed pneumonia in 79%
      (79/100 radiographs). The panel agreed with the staff in 77% (kappa = 0.76) and
      the resident in 23% (kappa = 0.43). The panel diagnosed pneumonia in 60% (60/100
      radiographs) with the following chest radiographic findings: 100% (60/60),
      increased opacity; 37% (22/60), air bronchograms; 72% (43/60), loss of vascular
      markings; 40% (24/60), silhouette sign; and 20% (12/60), linear opacities. The
      pneumonia was right sided in 52% (31/60), left sided in 37% (22/60), and
      bilateral in 11% (7/60). Right-sided pneumonias were equally distributed among
      the three lobes, and left-sided pneumonias had a lower-lobe predominance of 77%
      (17/22). Seventy-five percent (45/60) of pneumonias were segmental or smaller,
      and 82% (49/60) of chest radiographs showing pneumonia had both posteroanterior
      and lateral projections. The pneumonia was conspicuous on only one projection in
      43% (21/49); the posteroanterior view in 22% (11/49), and the lateral view in 20%
      (10/49). Eighty-one percent (81/100) of interpreting residents were PGY-3.
      CONCLUSION: Interpretation of chest radiographs for pneumonia by PGY-3 residents
      has a low error rate. Missed pneumonias often were segmental or smaller and
      conspicuous on only one projection.

PMID- 15866142
TI  - X-rays--a carcinogen.

PMID- 15866144
TI  - The neural basis of language talent in bilinguals.
AB  - In a recent paper, Chee et al. report differences in the patterns of brain
      activation and deactivation in bilinguals with different levels of proficiency in
      their second language. Most intriguingly, this research addressed the issue of
      the neural basis of phonological working memory (PWM), which is crucial in
      language acquisition, in subjects who were under comparable social pressure to be
      bilinguals. The results led the authors to suggest that a more readily available
      working memory system might correlate with the attainment of superior proficiency
      in a second language.

PMID- 15866145
TI  - Strategic behavior in monkeys.
AB  - In a recent paper, Lee et al. examined adaptive decision-making processes by
      training monkeys to play a competitive game against a computer programmed to play
      using various strategies. They found that the monkeys' responses were sensitive
      to the computer's strategies and consistent with reinforcement learning. Research
      such as this strongly complements current research in behavioral economics. We
      propose some potential future directions for this work, and put forward
      conjectures about what might be learned about decision-making in humans.

PMID- 15866146
TI  - What does change blindness teach us about consciousness?

PMID- 15866148
TI  - The emergence of competing modules in bilingualism.
AB  - How does the brain manage to store and process multiple languages without
      encountering massive interference and transfer? Unless we believe that bilinguals
      live in two totally unconnected cognitive worlds, we would expect far more
      transfer than actually occurs. However, imaging and lesion studies have not
      provided consistent evidence for the strict neuronal separation predicted by the
      theory of modularity. We suggest that emergentist theory offers a promising
      alternative. It emphasizes the competitive interplay between multiple languages
      during childhood and by focusing on the dual action of competition and
      entrenchment, avoids the need to invoke a critical period to account for age of
      acquisition effects in second-language learning. This view instantiates the motto
      formulated by Elizabeth Bates that 'modules are made, not born.'

PMID- 15866149
TI  - Elemental operations in vision.
AB  - Many cognitive tasks are serial in that they require several steps that have to
      be carried out in a sequence. Here, I outline a new theory of how these
      processing steps are implemented in vision by networks of neurons that span
      several areas of the cerebral cortex. The theory explains how individual neurons
      can contribute to the elementary processing steps, and also how several
      processing steps can be arranged in a sequence to form more complex visual
      routines, just as computer programs can be composed of sequences of instructions.
      Evidence in support of the theory comes from recent neurophysiological findings
      in monkeys engaged in complex visual tasks. It is likely that future work will
      allow these ideas to be generalized to other sensory modalities and cognitive
      functions.

PMID- 15866150
TI  - How our hands help us learn.
AB  - When people talk they gesture, and those gestures often reflect thoughts not
      expressed in their words. In this sense, gesture and the speech it accompanies
      can mismatch. Gesture-speech 'mismatches' are found when learners are on the
      verge of making progress on a task - when they are ready to learn. Moreover,
      mismatches provide insight into the mental processes that characterize learners
      when in this transitional state. Gesture is not just handwaving - it reflects how
      we think. However, evidence is mounting that gesture goes beyond reflecting our
      thoughts and can have a hand in changing those thoughts. We consider two ways in
      which gesture could change the course of learning: indirectly by influencing
      learning environments or directly by influencing learners themselves.

PMID- 15866151
TI  - The cognitive control of emotion.
AB  - The capacity to control emotion is important for human adaptation. Questions
      about the neural bases of emotion regulation have recently taken on new
      importance, as functional imaging studies in humans have permitted direct
      investigation of control strategies that draw upon higher cognitive processes
      difficult to study in nonhumans. Such studies have examined (1) controlling
      attention to, and (2) cognitively changing the meaning of, emotionally evocative
      stimuli. These two forms of emotion regulation depend upon interactions between
      prefrontal and cingulate control systems and cortical and subcortical emotion
      generative systems. Taken together, the results suggest a functional architecture
      for the cognitive control of emotion that dovetails with findings from other
      human and nonhuman research on emotion.

PMID- 15866152
TI  - Evolution of the brain and intelligence.
AB  - Intelligence has evolved many times independently among vertebrates. Primates,
      elephants and cetaceans are assumed to be more intelligent than 'lower' mammals,
      the great apes and humans more than monkeys, and humans more than the great apes.
      Brain properties assumed to be relevant for intelligence are the (absolute or
      relative) size of the brain, cortex, prefrontal cortex and degree of
      encephalization. However, factors that correlate better with intelligence are the
      number of cortical neurons and conduction velocity, as the basis for information
      processing capacity. Humans have more cortical neurons than other mammals,
      although only marginally more than whales and elephants. The outstanding
      intelligence of humans appears to result from a combination and enhancement of
      properties found in non-human primates, such as theory of mind, imitation and
      language, rather than from 'unique' properties.

PMID- 15866153
TI  - Opening a new can of worms: a large-scale RNAi screen in planarians.
AB  - In this issue of Developmental Cell, Reddien et al. describe the first large
      scale RNAi screen in freshwater planarians, classic models for regeneration
      studies. Their work paves the way for a detailed understanding of regeneration
      and tissue maintenance in these fascinating animals.

PMID- 15866154
TI  - A functional genomics approach to identify new regulators of Wnt signaling.
AB  - A recent study by used a genome-wide RNAi screen in Drosophila cells to identify
      238 candidate regulators of the Wnt-signaling pathway, most of which had not been
      previously connected to Wnt signaling. Supporting in vivo studies are in
      progress. The fact that such an impressive number of potential modulators had
      eluded detection in genetic screens underscores the potential of applying new,
      high-throughput approaches to old problems.

PMID- 15866155
TI  - Wnt/beta-catenin--a canonical tale of cell-fate choice in the vertebrate
      skeleton.
AB  - Three exciting papers in this issue of Developmental Cell provide new insights
      into the regulation of chondrocytic, osteoblastic, and osteoclastic
      differentiation during skeletal development and postnatal growth. The studies
      demonstrate that Wnt/beta-catenin signaling represents both a mechanism in
      mesenchymal precursor cells for selecting between chondrocytic and osteoblastic
      fates as well as a mechanism in osteoblasts for stimulating the production of an
      inhibitor of osteoclast formation.

PMID- 15866156
TI  - Identification of genes needed for regeneration, stem cell function, and tissue
      homeostasis by systematic gene perturbation in planaria.
AB  - Planarians have been a classic model system for the study of regeneration, tissue
      homeostasis, and stem cell biology for over a century, but they have not
      historically been accessible to extensive genetic manipulation. Here we utilize
      RNA-mediated genetic interference (RNAi) to introduce large-scale gene inhibition
      studies to the classic planarian system. 1065 genes were screened. Phenotypes
      associated with the RNAi of 240 genes identify many specific defects in the
      process of regeneration and define the major categories of defects planarians
      display following gene perturbations. We assessed the effects of inhibiting genes
      with RNAi on tissue homeostasis in intact animals and stem cell (neoblast)
      proliferation in amputated animals identifying candidate stem cell, regeneration,
      and homeostasis regulators. Our study demonstrates the great potential of RNAi
      for the systematic exploration of gene function in understudied organisms and
      establishes planarians as a powerful model for the molecular genetic study of
      stem cells, regeneration, and tissue homeostasis.

PMID- 15866157
TI  - Hierarchical and ontogenic positions serve to define the molecular basis of human
      hematopoietic stem cell behavior.
AB  - The molecular basis governing functional behavior of human hematopoietic stem
      cells (HSCs) is largely unknown. Here, using in vitro and in vivo assays, we
      isolate and define progenitors versus repopulating HSCs from multiple stages of
      human development for global gene expression profiling. Accounting for both the
      hierarchical relationship between repopulating cells and their progenitors, and
      the enhanced HSC function unique to early stages of ontogeny, the human homologs
      of Hairy Enhancer of Split-1 (HES-1) and Hepatocyte Leukemia Factor (HLF) were
      identified as candidate regulators of HSCs. Transgenic human hematopoietic cells
      expressing HES-1 or HLF demonstrated enhanced in vivo reconstitution ability that
      correlated to increased cycling frequency and inhibition of apoptosis,
      respectively. Our report identifies regulatory factors involved in HSC function
      that elicit their effect through independent systems, suggesting that a unique
      orchestration of pathways fundamental to all human cells is capable of
      controlling stem cell behavior.

PMID- 15866158
TI  - Integration of Notch 1 and calcineurin/NFAT signaling pathways in keratinocyte
      growth and differentiation control.
AB  - The Notch and Calcineurin/NFAT pathways have both been implicated in control of
      keratinocyte differentiation. Induction of the p21(WAF1/Cip1) gene by Notch 1
      activation in differentiating keratinocytes is associated with direct targeting
      of the RBP-Jkappa protein to the p21 promoter. We show here that Notch 1
      activation functions also through a second Calcineurin-dependent mechanism acting
      on the p21 TATA box-proximal region. Increased Calcineurin/NFAT activity by Notch
      signaling involves downregulation of Calcipressin, an endogenous Calcineurin
      inhibitor, through a HES-1-dependent mechanism. Besides control of the p21 gene,
      Calcineurin contributes significantly to the transcriptional response of
      keratinocytes to Notch 1 activation, both in vitro and in vivo. In fact, deletion
      of the Calcineurin B1 gene in the skin results in a cyclic alopecia phenotype,
      associated with altered expression of Notch-responsive genes involved in hair
      follicle structure and/or adhesion to the surrounding mesenchyme. Thus, an
      important interconnection exists between Notch 1 and Calcineurin-NFAT pathways in
      keratinocyte growth/differentiation control.

PMID- 15866159
TI  - Analysis of Notch function in presomitic mesoderm suggests a gamma-secretase
      independent role for presenilins in somite differentiation.
AB  - The role of Notch signaling in general and presenilin in particular was analyzed
      during mouse somitogenesis. We visualize cyclical production of activated Notch
      (NICD) and establish that somitogenesis requires less NICD than any other tissue
      in early mouse embryos. Indeed, formation of cervical somites proceeds in Notch1;
      Notch2-deficient embryos. This is in contrast to mice lacking all presenilin
      alleles, which have no somites. Since Nicastrin-, Pen-2-, and APH-1a-deficient
      embryos have anterior somites without gamma-secretase, presenilin may have a
      gamma-secretase-independent role in somitogenesis. Embryos triple homozygous for
      both presenilin null alleles and a Notch allele that is a poor substrate for
      presenilin (N1(V-->G)) experience fortuitous cleavage of N1(V-->G) by another
      protease. This restores NICD, anterior segmentation, and bilateral symmetry but
      does not rescue rostral/caudal identities. These data clarify multiple roles for
      Notch signaling during segmentation and suggest that the earliest stages of
      somitogenesis are regulated by both Notch-dependent and Notch-independent
      functions of presenilin.

PMID- 15866160
TI  - FGF signal interpretation is directed by Sprouty and Spred proteins during
      mesoderm formation.
AB  - Vertebrate gastrulation requires coordination of mesoderm specification with
      morphogenetic movements. While both of these processes require FGF signaling, it
      is not known how mesoderm specification and cell movements are coordinated during
      gastrulation. The related Sprouty and Spred protein families are recently
      discovered regulators of receptor tyrosine kinase signaling. We identified two
      genes for each family in Xenopus tropicalis: Xtsprouty1, Xtsprouty2, Xtspred1,
      and Xtspred2. In gain- and loss-of-function experiments we show that XtSprouty
      and XtSpred proteins modulate different signaling pathways downstream of the FGF
      receptor (FGFR), and consequently different developmental processes. Notably,
      XtSproutys inhibit morphogenesis and Ca(2+) and PKCdelta signaling, leaving MAPK
      activation and mesoderm specification intact. In contrast, XtSpreds inhibit MAPK
      activation and mesoderm specification, with little effect on Ca(2+) or PKCdelta
      signaling. These differences, combined with the timing of their developmental
      expression, suggest a mechanism to switch FGFR signal interpretation to
      coordinate mesoderm formation and cell movements during gastrulation.

PMID- 15866161
TI  - A vertebrate homolog of the cell cycle regulator Dbf4 is an inhibitor of Wnt
      signaling required for heart development.
AB  - Early stages of vertebrate heart development have been linked to Wnt signaling.
      Here we show in both gain- and loss-of-function experiments that XDbf4, a known
      regulator of Cdc7 kinase, is an inhibitor of the canonical Wnt signaling pathway.
      Depletion of endogenous XDbf4 protein did not disturb gastrulation movements or
      early organizer genes but resulted in embryos with morphologically defective
      heart and eyes and suppressed cardiac markers. These markers were restored by
      overexpressed XDbf4, or an XDbf4 mutant that inhibits Wnt signaling but lacks the
      ability to regulate Cdc7. This indicates that the function of XDbf4 in heart
      development is independent of its role in the cell cycle. Moreover, our data
      suggest that XDbf4 acts through the physical and functional interaction with
      Frodo, a context-dependent regulator of Wnt signaling. These findings establish
      an unexpected function for a vertebrate Dbf4 homolog and demonstrate the
      requirement for Wnt inhibition in early cardiac specification.

PMID- 15866162
TI  - Mutation of smooth muscle myosin causes epithelial invasion and cystic expansion
      of the zebrafish intestine.
AB  - Zebrafish meltdown (mlt) mutants develop cystic expansion of the posterior
      intestine as a result of stromal invasion of nontransformed epithelial cells.
      Positional cloning identified zebrafish smooth muscle myosin heavy chain (myh11)
      as the responsible gene. The mlt mutation constitutively activates the Myh11
      ATPase, which disrupts smooth muscle cells surrounding the posterior intestine.
      Adjacent epithelial cells ectopically express metalloproteinases, integrins, and
      other genes implicated in human cancer cell invasion. Knockdown and
      pharmacological inhibition of these genes restores intestinal structure in mlt
      mutants despite persistent smooth muscle defects. These data identify an
      essential role for smooth muscle signaling in the maintenance of epithelial
      architecture and support gene expression analyses and other studies that identify
      a role for stromal genes in cancer cell invasion. Furthermore, they suggest that
      high-throughput screens to identify regulators of cancer cell invasion may be
      feasible in zebrafish.

PMID- 15866163
TI  - Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating
      into chondrocytes.
AB  - Osteoblasts and chondrocytes are involved in building up the vertebrate skeleton
      and are thought to differentiate from a common mesenchymal precursor, the osteo
      chondroprogenitor. Although numerous transcription factors involved in
      chondrocyte and osteoblast differentiation have been identified, little is known
      about the signals controlling lineage decisions of the two cell types. Here, we
      show by conditionally deleting beta-catenin in limb and head mesenchyme that beta
      catenin is required for osteoblast lineage differentiation. Osteoblast precursors
      lacking beta-catenin are blocked in differentiation and develop into chondrocytes
      instead. In vitro experiments demonstrate that this is a cell-autonomous function
      of beta-catenin in an osteoblast precursor. Furthermore, detailed in vivo and in
      vitro loss- and gain-of-function analyses reveal that beta-catenin activity is
      necessary and sufficient to repress the differentiation of mesenchymal cells into
      Runx2- and Sox9-positive skeletal precursors. Thus, canonical Wnt/beta-catenin
      signaling is essential for skeletal lineage differentiation, preventing
      transdifferentiation of osteoblastic cells into chondrocytes.

PMID- 15866164
TI  - Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and
      chondrocyte differentiation during vertebrate skeletogenesis.
AB  - Chondrocytes and osteoblasts are two primary cell types in the skeletal system
      that are differentiated from common mesenchymal progenitors. It is believed that
      osteoblast differentiation is controlled by distinct mechanisms in
      intramembranous and endochondral ossification. We have found that ectopic
      canonical Wnt signaling leads to enhanced ossification and suppression of
      chondrocyte formation. Conversely, genetic inactivation of beta-catenin, an
      essential component transducing the canonical Wnt signaling, causes ectopic
      formation of chondrocytes at the expense of osteoblast differentiation during
      both intramembranous and endochondral ossification. Moreover, inactivation of
      beta-catenin in mesenchymal progenitor cells in vitro causes chondrocyte
      differentiation under conditions allowing only osteoblasts to form. Our results
      demonstrate that beta-catenin is essential in determining whether mesenchymal
      progenitors will become osteoblasts or chondrocytes regardless of regional
      locations or ossification mechanisms. Controlling Wnt/beta-catenin signaling is a
      common molecular mechanism underlying chondrocyte and osteoblast differentiation
      and specification of intramembranous and endochondral ossification.

PMID- 15866166
TI  - Computer simulations and image processing reveal length-dependent pulling force
      as the primary mechanism for C. elegans male pronuclear migration.
AB  - A male pronucleus migrates toward the center of an egg to reach the female
      pronucleus for zygote formation. This migration depends on microtubules growing
      from two centrosomes associated with the male pronucleus. Two mechanisms were
      previously proposed for this migration: a "pushing mechanism," which uses the
      pushing force resulting from microtubule polymerization, and a "pulling
      mechanism," which uses the length-dependent pulling force generated by minus-end
      directed motors anchored throughout the cytoplasm. We combined two computer
      assisted analyses to examine the relative contribution of these mechanisms to
      male pronuclear migration. Computer simulation revealed an intrinsic difference
      in migration behavior of the male pronucleus between the pushing and pulling
      mechanisms. In vivo measurements using image processing showed that the actual
      migration behavior in Caenorhabditis elegans confirms the pulling mechanism. A
      male pronucleus having a single centrosome migrated toward the single aster. We
      propose that the pulling mechanism is the primary mechanism for male pronuclear
      migration.

PMID- 15866165
TI  - Canonical Wnt signaling in differentiated osteoblasts controls osteoclast
      differentiation.
AB  - Inactivation of beta-catenin in mesenchymal progenitors prevents osteoblast
      differentiation; inactivation of Lrp5, a gene encoding a likely Wnt coreceptor,
      results in low bone mass (osteopenia) by decreasing bone formation. These
      observations indicate that Wnt signaling controls osteoblast differentiation and
      suggest that it may regulate bone formation in differentiated osteoblasts. Here,
      we study later events and find that stabilization of beta-catenin in
      differentiated osteoblasts results in high bone mass, while its deletion from
      differentiated osteoblasts leads to osteopenia. Surprisingly, histological
      analysis showed that these mutations primarily affect bone resorption rather than
      bone formation. Cellular and molecular studies showed that beta-catenin together
      with TCF proteins regulates osteoblast expression of Osteoprotegerin, a major
      inhibitor of osteoclast differentiation. These findings demonstrate that beta
      catenin, and presumably Wnt signaling, promote the ability of differentiated
      osteoblasts to inhibit osteoclast differentiation; thus, they broaden our
      knowledge of the functions Wnt proteins have at various stages of skeletogenesis.

PMID- 15866167
TI  - Binding of GEF-H1 to the tight junction-associated adaptor cingulin results in
      inhibition of Rho signaling and G1/S phase transition.
AB  - The activity of Rho GTPases is carefully timed to control epithelial
      proliferation and differentiation. RhoA is downregulated when epithelial cells
      reach confluence, resulting in inhibition of signaling pathways that stimulate
      proliferation. Here we show that GEF-H1/Lfc, a guanine nucleotide exchange factor
      for RhoA, directly interacts with cingulin, a junctional adaptor. Cingulin
      binding inhibits RhoA activation and signaling, suggesting that the increase in
      cingulin expression in confluent cells causes downregulation of RhoA by
      inhibiting GEF-H1/Lfc. In agreement, RNA interference of GEF-H1 or transfection
      of GEF-H1 binding cingulin mutants inhibit G1/S phase transition of MDCK cells,
      and depletion of cingulin by regulated RNA interference results in irregular
      monolayers and RhoA activation. These results indicate that forming epithelial
      tight junctions contribute to the downregulation of RhoA in epithelia by
      inactivating GEF-H1 in a cingulin-dependent manner, providing a molecular
      mechanism whereby tight junction formation is linked to inhibition of RhoA
      signaling.

PMID- 15866168
TI  - Repression of cell-cell fusion by components of the C. elegans vacuolar ATPase
      complex.
AB  - Cell-cell fusion initiates fertilization, sculpts tissues during animal
      development, reprograms stem cells to new differentiated states, and may be a key
      step in cancer progression. While cell fusion is tightly regulated, the
      mechanisms that limit fusion to appropriate partners are unknown. Here, we report
      that the fus-1 gene is essential to repress fusion of epidermal cells in C.
      elegans: in severe fus-1 mutants, all epidermal cells, except the lateral seam
      cells, inappropriately fuse into a single large syncytium. This hyperfusion
      requires EFF-1, an integral membrane protein essential for fusion of epidermal
      cells into discrete syncytia. FUS-1 is localized to the apical plasma membrane in
      all epidermal cells potentiated to undergo fusion, whereas it is virtually
      undetectable in nonfusing seam cells. fus-1 encodes the e subunit of the vacuolar
      H(+)-ATPase (V-ATPase), and loss of other V-ATPase subunits also causes
      widespread hyperfusion. These findings raise the possibility of manipulating cell
      fusion by altering V-ATPase activity.

PMID- 15866169
TI  - Arginine methylation an emerging regulator of protein function.
AB  - Arginine methylation is now coming out of the shadows of protein phosphorylation
      and entering the mainstream, largely due to the identification of the family of
      enzymes that lay down this modification. In addition, modification-specific
      antibodies and proteomic approaches have facilitated the identification of an
      array of substrates for the protein arginine methyltransferases. This review
      describes recent insights into the molecular processes regulated by arginine
      methylation in normal and diseased cells.

PMID- 15866170
TI  - Structural basis of Rho GTPase-mediated activation of the formin mDia1.
AB  - Diaphanous-related formins (DRFs) regulate dynamics of unbranched actin filaments
      during cell contraction and cytokinesis. DRFs are autoinhibited through
      intramolecular binding of a Diaphanous autoinhibitory domain (DAD) to a conserved
      N-terminal regulatory element. Autoinhibition is relieved through binding of the
      GTPase RhoA to the N-terminal element. We report the crystal structure of the
      dimeric regulatory domain of the DRF, mDia1. Dimerization is mediated by an
      intertwined six-helix bundle, from which extend two Diaphanous inhibitory domains
      (DIDs) composed of five armadillo repeats. NMR and biochemical mapping indicate
      the RhoA and DAD binding sites on the DID partially overlap, explaining
      activation of mDia1 by the GTPase. RhoA binding also requires an additional
      structurally independent segment adjacent to the DID. This regulatory
      construction, involving a GTPase binding site spanning a flexibly tethered arm
      and the inhibitory module, is observed in many autoinhibited effectors of Ras
      superfamily GTPases, suggesting evolutionary pressure for this design.

PMID- 15866171
TI  - AMP-activated protein kinase induces a p53-dependent metabolic checkpoint.
AB  - Replicative cell division is an energetically demanding process that can be
      executed only if cells have sufficient metabolic resources to support a doubling
      of cell mass. Here we show that proliferating mammalian cells have a cell-cycle
      checkpoint that responds to glucose availability. The glucose-dependent
      checkpoint occurs at the G(1)/S boundary and is regulated by AMP-activated
      protein kinase (AMPK). This cell-cycle arrest occurs despite continued amino acid
      availability and active mTOR. AMPK activation induces phosphorylation of p53 on
      serine 15, and this phosphorylation is required to initiate AMPK-dependent cell
      cycle arrest. AMPK-induced p53 activation promotes cellular survival in response
      to glucose deprivation, and cells that have undergone a p53-dependent metabolic
      arrest can rapidly reenter the cell cycle upon glucose restoration. However,
      persistent activation of AMPK leads to accelerated p53-dependent cellular
      senescence. Thus, AMPK is a cell-intrinsic regulator of the cell cycle that
      coordinates cellular proliferation with carbon source availability.

PMID- 15866172
TI  - Conserved docking site is essential for activation of mammalian MAP kinase
      kinases by specific MAP kinase kinase kinases.
AB  - Mammalian mitogen-activated protein kinase (MAPK) cascades control various
      cellular events, ranging from cell growth to apoptosis, in response to external
      stimuli. A conserved docking site, termed DVD, is found in the mammalian MAP
      kinase kinases (MAPKKs) belonging to the three major subfamilies, namely MEK1,
      MKK4/7, and MKK3/6. The DVD sites bind to their specific upstream MAP kinase
      kinase kinases (MAPKKKs), including MTK1 (MEKK4), ASK1, TAK1, TAO2, MEKK1, and
      Raf-1. DVD site is a stretch of about 20 amino acids immediately on the C
      terminal side of the MAPKK catalytic domain. Mutations in the DVD site strongly
      inhibited MAPKKs from binding to, and being activated by, their specific MAPKKKs,
      both in vitro and in vivo. DVD site mutants could not be activated by various
      external stimuli in vivo. Synthetic DVD oligopeptides inhibited specific MAPKK
      activation, both in vitro and in vivo, demonstrating the critical importance of
      the DVD docking in MAPK signaling.

PMID- 15866173
TI  - Transcriptional silencing of nonsense codon-containing immunoglobulin minigenes.
AB  - Cells possess mechanisms to prevent synthesis of potentially deleterious
      truncated proteins caused by premature translation-termination codons (PTCs).
      Here, we show that PTCs can induce silencing of transcription of its cognate
      gene. We demonstrate for immunoglobulin (Ig)-mu minigenes expressed in HeLa cells
      that this transcriptional silencing is PTC specific and reversible by treatment
      of the cells with histone deacetylase inhibitors. Furthermore, PTC-containing Ig
      mu minigenes are significantly more associated with K9-methylated histone H3 and
      less associated with acetylated H3 than the PTC-free Ig-mu minigene. This
      nonsense-mediated transcriptional gene silencing (NMTGS) is also observed with an
      Ig-gamma minigene, but not with several classic NMD reporter genes, suggesting
      that NMTGS might be specific for Ig genes. NMTGS represents a nonsense
      surveillance mechanism by which truncation of a gene's open reading frame (ORF)
      induces transcriptional silencing through chromatin remodeling. Remarkably, NMTGS
      is inhibited by overexpression of the putative siRNase 3'hExo, suggesting that
      siRNA-like molecules are involved in NMTGS.

PMID- 15866174
TI  - Interaction of Era with the 30S ribosomal subunit implications for 30S subunit
      assembly.
AB  - Era (E. coliRas-like protein) is a highly conserved and essential GTPase in
      bacteria. It binds to the 16S ribosomal RNA (rRNA) of the small (30S) ribosomal
      subunit, and its depletion leads to accumulation of an unprocessed precursor of
      the 16S rRNA. We have obtained a three-dimensional cryo-electron microscopic map
      of the Thermus thermophilus 30S-Era complex. Era binds in the cleft between the
      head and platform of the 30S subunit and locks the subunit in a conformation that
      is not favorable for association with the large (50S) ribosomal subunit. The RNA
      binding KH motif present within the C-terminal domain of Era interacts with the
      conserved nucleotides in the 3' region of the 16S rRNA. Furthermore, Era makes
      contact with several assembly elements of the 30S subunit. These observations
      suggest a direct involvement of Era in the assembly and maturation of the 30S
      subunit.

PMID- 15866175
TI  - Translational regulatory mechanisms generate N-terminal glucocorticoid receptor
      isoforms with unique transcriptional target genes.
AB  - Glucocorticoids regulate diverse physiological functions ranging from mitosis to
      apoptosis, although only one glucocorticoid receptor (GR) gene has been
      discovered. We report here that one single GR mRNA species unexpectedly produces
      at least eight functional GR N-terminal isoforms via translational mechanisms.
      These GR isoforms display diverse cytoplasm-to-nucleus trafficking patterns and
      distinct transcriptional activities. In human osteosarcoma cells, the
      transcriptional responses to glucocorticoids closely reflect the identity and
      abundance of the GR isoforms. In addition, each GR isoform regulates both a
      common and a unique set of genes in the same cell. Interestingly, the levels of
      these GR isoforms differ significantly among tissues. Based on these
      observations, we propose that cell-type specific GR isoforms generate specificity
      in glucocorticoid control of transcription in different tissues.

PMID- 15866176
TI  - A ligand-activated nuclear localization signal in cellular retinoic acid binding
      protein-II.
AB  - Primary sequences of proteins often contain motifs that serve as "signatures" for
      subcellular targeting, such as a nuclear localization signal (NLS). However, many
      nuclear proteins do not harbor a recognizable NLS, and the pathways that mediate
      their nuclear translocation are unknown. This work focuses on CRABP-II, a
      cytosolic protein that moves to the nucleus upon binding of retinoic acid. While
      CRABP-II does not contain an NLS in its primary sequence, such a motif could be
      recognized in the protein's tertiary structure. We map the retinoic acid-induced
      structural rearrangements that result in the presence of this NLS in holo- but
      not apo-CRABP-II. The signal, whose three-dimensional configuration aligns
      strikingly well with a "classical" NLS, mediates ligand-induced association of
      CRABP-II with importin alpha and is critical for nuclear localization of the
      protein. The ligand-controlled NLS "switch" of CRABP-II may represent a general
      mechanism for posttranslational regulation of the subcellular distribution of a
      protein.

PMID- 15866177
TI  - The structure of the nuclear export receptor Cse1 in its cytosolic state reveals
      a closed conformation incompatible with cargo binding.
AB  - Cse1 mediates nuclear export of importin alpha, the nuclear localization signal
      (NLS) import adaptor. We report the 3.1 A resolution structure of cargo-free
      Cse1, representing this HEAT repeat protein in its cytosolic state. Cse1 is
      compact, consisting of N- and C-terminal arches that interact to form a ring.
      Comparison with the structure of cargo-bound Cse1 shows a major conformational
      change leading to opening of the structure upon cargo binding. The largest
      structural changes occur within a hinge region centered at HEAT repeat 8. This
      repeat contains a conserved insertion that connects the RanGTP and importin alpha
      contact sites and that is essential for binding. In the cargo-free state, the
      RanGTP binding sites are occluded and the importin alpha sites are distorted.
      Mutations that destabilize the N- to C-terminal interaction uncouple importin
      alpha and Ran binding, suggesting that the closed conformation prevents
      association with importin alpha.

PMID- 15866178
TI  - Function of a eukaryotic transcription activator during the transcription cycle.
AB  - Site-specific photocrosslinkers positioned within the central transcription
      activating region of yeast Gcn4 were used to identify, in an unbiased way, three
      polypeptides in direct physical proximity to the activator during the process of
      transcription activation. Crosslinking was specific and did not change during
      different steps of the transcription cycle. The crosslinking targets were
      identified as Tra1, Gal11, and Taf12, subunits of four complexes (SAGA, NuA4,
      Mediator, and TFIID) known to play a role in gene regulation. Using this
      crosslinking assay, an activating region mutant, and extracts depleted of
      individual complexes containing the crosslinking targets, we found that contact
      with Tra1/SAGA is critical for activation, Gal11 contact has a modest effect on
      activation, and contact with TFIID and NuA4 is of little or no importance for
      activation under our conditions. Thus, a single activating region contacts
      multiple factors, and each contact makes differential contributions to
      transcriptional activation.

PMID- 15866180
TI  - Suricate alarm calls signal predator class and urgency.

PMID- 15866179
TI  - Mechanism of Aurora B activation by INCENP and inhibition by hesperadin.
AB  - Aurora family serine/threonine kinases control mitotic progression, and their
      deregulation is implicated in tumorigenesis. Aurora A and Aurora B, the best
      characterized members of mammalian Aurora kinases, are approximately 60%
      identical but bind to unrelated activating subunits. The structure of the complex
      of Aurora A with the TPX2 activator has been reported previously. Here, we report
      the crystal structure of Aurora B in complex with the IN-box segment of the inner
      centromere protein (INCENP) activator and with the small molecule inhibitor
      Hesperadin. The Aurora B:INCENP complex is remarkably different from the Aurora
      A:TPX2 complex. INCENP forms a crown around the small lobe of Aurora B and
      induces the active conformation of the T loop allosterically. The structure
      represents an intermediate state of activation of Aurora B in which the Aurora B
      C-terminal segment stabilizes an open conformation of the catalytic cleft, and a
      critical ion pair in the kinase active site is impaired. Phosphorylation of two
      serines in the carboxyl terminus of INCENP generates the fully active kinase.

PMID- 15866181
TI  - From corpora to cuttlefish.
AB  - The 7th Neural Computation and Psychology Workshop was held at the University of
      Sussex, Brighton, on 17-19 September 2001. The theme was 'Connectionist Models of
      Cognition and Perception'.

PMID- 15866189
TI  - Revising hypotheses does not indicate a flawed approach. Reply to Bolhuis and
      Macphail.

PMID- 15866182
TI  - Independent component analysis: an introduction.
AB  - Independent component analysis (ICA) is a method for automatically identifying
      the underlying factors in a given data set. This rapidly evolving technique is
      currently finding applications in analysis of biomedical signals (e.g. ERP, EEG,
      fMRI, optical imaging), and in models of visual receptive fields and separation
      of speech signals. This article illustrates these applications, and provides an
      informal introduction to ICA.

PMID- 15866190
TI  - RAP: a new framework for visual categorization.
AB  - Cognitive science might almost be defined as several disciplines communicating
      their different perspectives on the mind, the common object of study. However,
      domain-specific concepts and techniques can prevent, rather than foster, a
      communication of viewpoints. In this article, we develop a new framework for
      visual categorization in which the interaction between Represented (R)
      information and Available (A) information determine the Potent (P) information
      (symbolically, R ? A approximately P). We argue and illustrate that this
      framework helps to establish a common language to articulate issues common to low
      , mid-, and high-level vision. More importantly, we present new techniques with
      which to visualize the so-far elusive constructs of representation and potent
      information.

PMID- 15866191
TI  - Towards a neural basis of auditory sentence processing.
AB  - Functional dissociations within the neural basis of auditory sentence processing
      are difficult to specify because phonological, syntactic and semantic information
      are all involved when sentences are perceived. In this review I argue that
      sentence processing is supported by a temporo-frontal network. Within this
      network, temporal regions subserve aspects of identification and frontal regions
      the building of syntactic and semantic relations. Temporal analyses of brain
      activation within this network support syntax-first models because they reveal
      that building of syntactic structure precedes semantic processes and that these
      interact only during a later stage.

PMID- 15866192
TI  - Event categorization in infancy.
AB  - Recent research suggests that one of the mechanisms that contribute to infants'
      acquisition of their physical knowledge is the formation of event categories,
      such as occlusion and containment. Some of this research compared infants'
      identification of similar variables in different event categories. Marked
      developmental lags were found, suggesting that infants acquire event-specific
      rather than event-general expectations. Other research - on variable priming,
      perseveration, and object individuation - presented infants with successive
      events from the same or from different event categories. To understand the world
      as it unfolds, infants must not only represent each separate event, but also link
      successive events; this research begins to explore how infants respond to
      multiple events over time.

PMID- 15866193
TI  - Observing the transformation of experience into memory.
AB  - The ability to remember one's past depends on neural processing set in motion at
      the moment each event is experienced. Memory formation can be observed by
      segregating neural responses according to whether or not each event is recalled
      or recognized on a subsequent memory test. Subsequent memory analyses have been
      performed with various neural measures, including brain potentials extracted from
      intracranial and extracranial electroencephalographic recordings, and hemodynamic
      responses from functional magnetic resonance imaging. Neural responses can
      predict which events, and which aspects of those events, will be subsequently
      remembered or forgotten, thereby elucidating the neurocognitive processes that
      establish durable episodic memories.

PMID- 15866194
TI  - A multi-photon window onto neuronal-glial-vascular communication.
AB  - The cellular components of the brain are neurons, glia and vascular cells. These
      three entities form a metabolic network to sustain brain activity. Interactions
      among these cell types have been studied extensively in vitro, where the cells
      are easily accessible to physiological and pharmacological manipulations. With
      the advent of optical tools, it has become possible to investigate the cerebral
      metabolic network in vitro at the cellular and subcellular levels. However, the
      metabolic and homeostatic nature of neuronal-glial-vascular interactions must
      eventually be examined in vivo, and multi-photon imaging now provides a means to
      monitor neurovascular units in living experimental animals.

PMID- 15866195
TI  - SOX2 functions in adult neural stem cells.
AB  - Sox2 is expressed highly in the neuroepithelium of the developing CNS and has
      been shown to function in neural stem cells. Because Sox2-null mutant mice fail
      to develop beyond implantation, the role of SOX2 in the CNS has lacked
      validation. A new genetic model addresses the role of SOX2 in the adult brain and
      provides evidence that it is involved in the maintenance of neurons in specific
      regions, in the proliferation and/or maintenance of neural stem cells, and in
      neurogenesis.

PMID- 15866196
TI  - Timing in synaptic plasticity: from detection to integration.
AB  - Timing of cellular and subcellular events contributes to spiking-induced
      modification of synapses in a variety of ways. Initially, the timing of
      presynaptic and postsynaptic action potentials must be translated into signals
      that can initiate intracellular processes. Recent experimental and computational
      findings suggest that the spatiotemporal details of such signals, in particular
      the time courses and locations of postsynaptic Ca(2+) transients, might
      themselves be crucial for driving potentiation and depression modules that
      interact in a time-dependent way to determine plasticity outcomes. On longer
      timescales, the effects of multiple spikes are integrated in a nonlinear manner,
      yielding non-intuitive plasticity results that are likely to be sensitive to
      local conditions and, finally, additional elements must be called into action to
      stabilize changes in synaptic strengths. This review is part of the TINS Synaptic
      Connectivity series.

PMID- 15866197
TI  - Homeostatic plasticity and NMDA receptor trafficking.
AB  - Learning, memory and brain development are associated with long-lasting
      modifications of synapses that are guided by specific patterns of neuronal
      activity. Such modifications include classical Hebbian plasticities (such as long
      term potentiation and long-term depression), which are rapid and synapse
      specific, and others, such as synaptic scaling and metaplasticity, that work over
      longer timescales and are crucial for maintaining and orchestrating neuronal
      network function. The cellular mechanisms underlying Hebbian plasticity have been
      well studied and involve rapid changes in the trafficking of highly mobile AMPA
      receptors. An emerging concept is that activity-dependent alterations in NMDA
      receptor trafficking contribute to homeostatic plasticity at central
      glutamatergic synapses.

PMID- 15866198
TI  - Genetics moving to neuronal networks.
AB  - Neuronal circuits are essential components of the nervous system and determine
      various body functions. To understand how neuronal circuits operate it is
      necessary to identify the participating neuronal subpopulations and to dissect
      the function of the neurons at the molecular level. The locomotor central pattern
      generator that coordinates body movements is well suited for elucidating the
      assembly and identity of the participating neurons. Remarkable advances in the
      field of genetics are making studies in neuroscience more efficient and precise
      so that now, using nematode worms, fruit flies, zebrafish and mice as model
      organisms, a genetic approach can be used to identify molecules and neurons
      crucial for locomotor network functionality.

PMID- 15866199
TI  - Integrating new neurons into the adult olfactory bulb: joining the network, life
      death decisions, and the effects of sensory experience.
AB  - In contrast to the situation in the developing brain, neurons born during
      adulthood must integrate into established neuronal networks characterized by
      ongoing activity. For sensory systems, this neuronal activity is driven mainly by
      external stimuli that can lead to experience-dependent morpho-functional changes
      in adult circuits. Here, we describe new insights into the mechanisms by which
      sensory experience might govern the targeting of adult-generated neurons to
      appropriate regions, their differentiation into distinct neuronal subtypes, and
      finally their survival in the adult olfactory bulb. We propose not only that
      neurogenesis depends on the degree of sensory experience, but also that new
      neurons bring unique features to the operational network, allowing a continuous
      adjustment of information processing in response to an ever-changing external
      word.

PMID- 15866200
TI  - Auditory thalamocortical transformation: structure and function.
AB  - Communicative, predatory, and reproductive behaviors rely on the auditory
      thalamocortical system, a key nexus that combines, transforms, and distributes
      virtually all acoustic information relevant to survival. The rules of
      connectivity for this complex network, both anatomically and functionally, are
      only beginning to be uncovered. Although the auditory thalamocortical system
      shares many features with other modalities, its connectivity and information
      processing principles differ from those of other modalities in many ways. Some
      physiological and anatomical bases for these differences are the subject of this
      review.

PMID- 15866201
TI  - Multisensory spatial interactions: a window onto functional integration in the
      human brain.
AB  - Incoming signals from different sensory modalities are initially processed in
      separate brain regions. But because these different signals can arise from common
      events or objects in the external world, integration between them can be useful.
      Such integration is subject to spatial and temporal constraints, presumably
      because a common source is more likely for information arising from around the
      same place and time. This review focuses on recent neuroimaging data concerning
      spatial aspects of multisensory integration in the human brain. These findings
      indicate not only that multisensory integration involves anatomical convergence
      from sensory-specific ('unimodal') cortices into multisensory ('heteromodal')
      brain areas, but also that multisensory spatial interactions can affect even so
      called 'unimodal' brain regions. Such findings call for a revision of traditional
      assumptions about multisensory processing in the brain.

PMID- 15866202
TI  - Emerging properties of cannabinoid medicines in management of multiple sclerosis.
AB  - Use of cannabis as a medicine for numerous conditions has a well-documented
      history stretching back thousands of years. With the identification of an
      endogenous system of receptors and ligands in recent years, abundant experimental
      data have reinforced the anecdotal claims of people who perceive medicinal
      benefit from the currently illegal consumption of cannabis. This, combined with
      data from recent clinical trials, points to the prospect of cannabis as a
      medication in the treatment of multiple sclerosis and numerous other medical
      conditions.

PMID- 15866204
TI  - Helicobacter pylori, T cells and cytokines: the "dangerous liaisons".
AB  - Helicobacter pylori infection is the major cause of gastroduodenal pathologies,
      but only a minority of infected patients develop chronic and life threatening
      diseases, as peptic ulcer, gastric cancer, B-cell lymphoma, or autoimmune
      gastritis. The type of host immune response against H. pylori is crucial for the
      outcome of the infection. A predominant H. pylori-specific Th1 response,
      characterized by high IFN-gamma, TNF-alpha, and IL-12 production associates with
      peptic ulcer, whereas combined secretion of both Th1 and Th2 cytokines are
      present in uncomplicated gastritis. Gastric T cells from MALT lymphoma exhibit
      abnormal help for autologous B-cell proliferation and reduced perforin- and Fas
      Fas ligand-mediated killing of B cells. In H. pylori-infected patients with
      autoimmune gastritis cytolytic T cells infiltrating the gastric mucosa cross
      recognize different epitopes of H. pylori proteins and H+K+ ATPase autoantigen.
      These data suggest that peptic ulcer can be regarded as a Th1-driven
      immunopathological response to some H. pylori antigens, whereas deregulated and
      exhaustive H. pylori-induced T cell-dependent B-cell activation can support the
      onset of low-grade B-cell lymphoma. Alternatively, H. pylori infection may lead
      in some individuals to gastric autoimmunity via molecular mimicry.

PMID- 15866205
TI  - CD4+CD25+ suppressor T cells regulate pathogen induced inflammation and disease.
AB  - A key suppressor role has recently been ascribed to the natural CD4+CD25+
      regulatory T cells (Treg), the removal of which leads to the development of
      autoimmune disease and aggravated pathogen-induced inflammation in otherwise
      normal hosts. The repertoire of antigen specificities of Treg is as broad as that
      of naive T cells, recognizing both self and non-self antigens, enabling Treg to
      control a broad range of immune responses. Although widely acknowledged to play a
      role in the maintenance of self-tolerance, recent studies indicate that Treg can
      be activated and expanded against bacterial, viral and parasite antigens in vivo.
      Such pathogen-specific Treg can prevent infection-induced immunopathology but may
      also increase the load of infection and prolong pathogen persistence by
      suppressing protective immune responses. This review discusses the role of Treg
      in the prevention of exaggerated inflammation favoring chronicity in bacterial or
      fungal infections and latency in viral infections. Special attention is given to
      the role of Treg in the modulation of gastric inflammation induced by
      Helicobacter pylori infection. Findings in both experimentally infected mice and
      humans with natural infection indicate that Treg are important in protecting the
      H. pylori-infected host against excessive gastric inflammation and disease
      symptoms but on the negative side promote bacterial colonization at the gastric
      and duodenal mucosa which may increase the risk in H. pylori-infected individuals
      to develop duodenal ulcers.

PMID- 15866206
TI  - Role of inflammation in gastrointestinal tract in aetiology and pathogenesis of
      idiopathic parkinsonism.
AB  - Idiopathic parkinsonism (IP) is a common disorder, conventionally regarded as
      neurodegenerative. Its cardinal features, poverty and slowness of movement,
      muscle rigidity, postural abnormality and a characteristic tremor, are associated
      with loss of dopaminergic neurones in the substantia nigra of the brain. Genetic
      factors explain only a minority of cases, and a common toxic environmental insult
      remains elusive. We propose that IP is a systemic disorder resulting from a
      ubiquitous peripheral infection, and that only the tip of the iceberg comes to
      diagnosis. There is evidence for inflammatory/immune activation peripherally and
      in the brain. We have used statistical modelling to explore links with non
      specific and specific systemic markers of inflammation/infection in IP probands,
      and explore whether their partners and siblings have a frank or pre-presentation
      parkinsonian state. Critical to this approach is continuous objective measures of
      the facets of IP. Hypotheses on causality and mechanism are based on the
      statistical models. There is pathological and clinical evidence for direct
      involvement of the gastrointestinal tract in IP. The candidacy of Helicobacter
      pylori infection as a trigger event or driving infection is relatively high. We
      have found that eliminating infection in late parkinsonism with cachexia, a stage
      usually considered intractable, can result in a U-turn. However, eradication
      therapy may not provide a complete solution. Persistence of antibody against
      cytotoxin-associated antigen (CagA), increases the predicted probability of being
      labelled as having parkinsonism. Evidence for autoimmunity and immunocompromise
      is used to build schemes for the natural history. We conclude that current
      classifications of neuropsychiatric disease may not prove the best with respect
      to defining sub-clinical disease, prophylaxis or halting progression.

PMID- 15866207
TI  - Helicobacter pylori disulphide reductases: role in metronidazole reduction.
AB  - Disulphide reductases play an important role in maintaining intracellular redox
      potential. Three disulphide reductase activities were identified in Helicobacter
      pylori, which used dithiobis-2-nitrobenzoic acid, glutathione or l-cystine and
      ferredoxin as substrates. The kinetic parameters of these activities were
      determined and it was demonstrated that the reductase activities were inhibited
      by the presence of metronidazole. Substrate competition experiments served to
      show inhibition of metronidazole reduction by dithiobis-2-nitrobenzoic acid,
      glutathione and ferredoxin in lysates from metronidazole susceptible and
      resistant matched pairs of strains. The study demonstrated that the activities of
      three disulphide reductases were modulated by the presence of metronidazole, and
      that metronidazole reduction was inhibited by the presence of disulphide
      reductase substrates.

PMID- 15866208
TI  - Helicobacter pylori VacA cytotoxin interacts with fibronectin and alters HeLa
      cell adhesion and cytoskeletal organization in vitro.
AB  - Helicobacter pylori vacuolating cytotoxin VacA causes multiple effects on
      epithelial cell function and morphology, but the effects of VacA on signal
      transduction pathways and the cytoskeleton have not been investigated in detail.
      In this study, we analyzed the effects of native VacA on HeLa and AGS cell
      adhesion to fibronectin and laminin under serum-free conditions. Confocal
      microscopic examination revealed increased number of cells with rounded
      morphology and inhibition of actin fiber formation, in the presence of VacA. VacA
      binds to fibronectin in vitro in a dose-dependent manner. This interaction was
      partly inhibited by a peptide containing an arginine-glycine-aspartic acid motif.
      The adhesion of HeLa cells to fibronectin, but not to laminin, was decreased in
      the presence of VacA. Thus, VacA may interact with fibronectin and influence
      integrin receptor-induced cell signaling and cytoskeleton-dependent cell
      functions.

PMID- 15866209
TI  - Correlation of the Helicobacter pylori adherence factor BabA with duodenal ulcer
      disease in four European countries.
AB  - Helicobacter pylori strains harboring the vacAs1, cagA and babA2 have been
      associated with ulcer disease (UD). We compared the prevalence of these different
      genotypes and adhesive properties in H. pylori infected patients with UD in four
      European countries. Genomic DNA was isolated from 314 H. pylori strains: Germany
      (GER; n=92), Sweden (SWE, n=74), Portugal (POR, n=91) and Finland (FIN, n=57).
      The frequencies of babA2 genotype varied from 35% to 60%. Triple-positive strains
      (vacAs1+, cagA+ and babA2+) were significantly associated with UD in GER and POR
      and were closely correlated with UD in FIN, but not in SWE. Classification as
      triple-positive strains had a higher specificity for detection of UD in GER, POR
      and FIN than type1 or cagA+ strains. In vitro adhesion assays revealed that
      Swedish strains showed high adhesion properties and were thus correlated with the
      diagnosis of UD, although PCR detected the babA2 gene at lower frequencies and
      failed to show a correlation with UD. This finding appears to reflect allelic
      variations of the babA2 gene in SWE, although adhesive properties of the strains
      are retained.

PMID- 15866210
TI  - Novel plasmids for gene expression analysis and for genetic manipulation in the
      gastric pathogen Helicobacter pylori.
AB  - To facilitate gene expression analysis in the human gastric pathogen Helicobacter
      pylori, we constructed the plasmids pHPLAC-KAN and pHPLAC-CAT containing a
      promoterless Escherichia coli lacZ gene located upstream from the antibiotic
      resistance genes aphA-3 or cat, respectively. The suitability of the plasmids for
      H. pylori mutagenesis and gene expression analysis was evaluated by plasmid
      integration into the genome of H. pylori strain 1061 by single homologous
      recombination, using the rpl9 gene encoding ribosomal protein L9 as target. By
      monitoring beta-galactosidase production from the resulting rpl9::lacZ fusion, it
      was demonstrated that H. pylori rpl9 displays the classical growth phase
      dependent regulation of components of the protein synthesis machinery, as beta
      galactosidase production dropped fivefold in the stationary growth phase. The
      plasmids described in this study extend our methodological repertoire for genetic
      modification and molecular analysis of H. pylori, and may also be of use for
      other bacteria, as the resistance cassettes and the lacZ gene are active in the
      related Campylobacter species.

PMID- 15866211
TI  - Identification of a new sialic acid-binding protein in Helicobacter pylori.
AB  - A novel sialic acid-specific lectin has been isolated from Helicobacter pylori
      lysate using fetuin-agarose affinity chromatography followed by cleavage of the
      alpha(2,3) and alpha(2,6) linkages of sialic acids using neuraminidase. The
      protein had a molecular weight of 17.5 kDa on sodium dodecyl sulfate (SDS)
      polyacrylamide gel electrophoresis (PAGE) and was identified by matrix-assisted
      laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry to be
      protein of unknown function with gene number HP0721. Recombinant HP0721 was shown
      to bind to fetuin-agarose and sialic acid-containing glycosphingolipids on thin
      layer plates suggesting this protein may represent another sialic acid-specific
      adhesin of H. pylori. A H. pylori mutant defective for HP0721 was generated and
      its ability to bind to human AGS cells assayed.

PMID- 15866212
TI  - Macrolide-affected Toll-like receptor 4 expression from Helicobacter pylori
      infected monocytes does not modify interleukin-8 production.
AB  - Macrolide antibiotics have an anti-inflammatory effect by suppressing
      lipopolysaccharide-induced IL-8 production. IL-8 secretion from monocytes is
      observed in Helicobacter pylori infection. Although cag gene products are known
      to induce IL-8 secretion, whether other bacterial substances can initiate the
      reaction is not determined. In this study, we show that clarithromycin induced
      down-regulation of Toll-like receptor 4 expression and did not lead to a decrease
      in IL-8 production and H. pylori lipopolysaccharide. However, Toll-like receptor
      4 activation was possibly not the main cause in the induction of inflammation
      during H. pylori infection.

PMID- 15866213
TI  - Characterization of the PCR inhibitory effect of bile to optimize real-time PCR
      detection of Helicobacter species.
AB  - The inhibitory effect of human and porcine bile samples to detect Helicobacter
      DNA was studied by adding different concentrations of bile samples to PCR
      mixtures of six thermostable DNA polymerases containing cagA specific primers and
      Helicobacter pylori DNA. PCR products were amplified by using the Rotorgene
      system and SYBR Green I. Among the six DNA polymerases tested, rTth had the
      lowest sensitivity to bile inhibitors, whereas Taq and Tfl had the highest
      sensitivity. Bile proteins did not inhibit AmpliTaq DNA polymerase, whereas the
      fraction containing mainly bile acids and their salts inhibited the amplification
      capacity of AmpliTaq. Heating human bile at 98 degrees C and adding casein and
      formamide to the reaction mixture reduced the PCR inhibitory effect of bile.
      Therefore, a pre-PCR treatment based on dilution and heating of bile, adding
      casein and formamide to the reaction mixture of rTth DNA polymerase was found
      efficient to amplify DNA directly in bile.

PMID- 15866214
TI  - Mutational analysis of the Helicobacter pylori carbonic anhydrases.
AB  - In the gastric microenvironment, Helicobacter pylori is exposed to bicarbonate,
      urea and acid. Here it is demonstrated that both H. pylori carbonic anhydrases
      (CAs) are required for maintaining urease activity and therefore influence H.
      pylori urea resistance at neutral pH. Furthermore, the beta-CA is required for
      acid resistance as indicated by a growth defect of the corresponding mutant at
      low pH. The alpha- and beta-CA mutants as well as the double mutant were more
      resistant to bicarbonate, indicating that both enzymes are involved in
      bicarbonate metabolism. These phenotypes support important CA-functions in H.
      pylori urea and bicarbonate metabolism and acid resistance. Thus, both CA enzymes
      might be required for survival in the gastric niche.

PMID- 15866215
TI  - Helicobacter pylori antibodies and gastric cancer: a gender-related difference.
AB  - Helicobacter pylori has been proposed as a causative agent of gastric cancer. The
      aim of this study was to define serum antibodies response against different H.
      pylori antigens in patients with gastric cancer. Serum samples were collected
      from 115 Lithuanian patients with non-cardia gastric cancer and 110 age- and sex
      matched controls without cancer. Heat-stable, low-molecular-mass, and outer
      membrane proteins were used as antigens to analyze serum IgG antibody response
      against H. pylori by enzyme-linked immunosorbent assay. Seroprevalence of H.
      pylori using low-molecular-mass antigen was significantly higher in gastric
      cancer patients, compared to controls (77% versus 57%, p<0.05). Significant
      differences in the prevalence of H. pylori infection between gastric cancer
      patients and controls were found in females using all three studied antigens:
      heat-stable (98% versus 84%, p<0.05), low-molecular-mass (88% versus 48%, p<0.05)
      and outer membrane proteins (78% versus 57%, p<0.05). In males, no significant
      differences were revealed between gastric cancer patients and controls. There may
      be other cofactors in addition to H. pylori that are important for the
      development of gastric cancer. H. pylori seems, however, to be a more important
      for development of gastric cancer in females than in males or males may have more
      confounding risk factors for gastric cancer than females.

PMID- 15866216
TI  - Expression of matrix metalloprotease-2, -7 and -9 on human colon, liver and bile
      duct cell lines by enteric and gastric Helicobacter species.
AB  - Gastric and enteric Helicobacter species have been associated with malignant and
      inflammatory diseases of the stomach, liver, gall bladder and intestine. Matrix
      metalloproteinases (MMPs) participate in degradation of extracellular matrix,
      which allows bacteria to come in contact with and interact with the cells.
      Enhanced level of MMPs facilitates metastasis and cell invasion of tumor cells by
      removal of physical barriers, as well as modulation of biologic activities of the
      proteins residing in the extracellular matrix. The aim of this study was to
      evaluate the effect of gastric and enteric Helicobacter on induction of MMPs in
      hepatocytes and epithelial cells of gall bladder and colon. Human hepatocytes
      HepG2, gall bladder epithelial cells TFK-1, and colon epithelial cells HT29 were
      infected with strains of H. pylori cagA+, cagE+, H. pylori cagA-, cagE-, H.
      pullorum, H. cholecystus, H. bilis and H. hepaticus. Protein levels of MMPs were
      analyzed by enzyme-linked immunosorbent assay and immunohistochemistry. Reverse
      transcription-quantitative polymerase chain reaction was used to study mRNA
      levels. Increased expression of MMP-2 and MMP-9 was observed on HepG2, TFK-1 and
      HT29 infected with H. pylori cagA+, cagE+ and H. cholecystus strains. H. pylori
      cagA+, cagE+, H. cholecystus, H. pullorum, H. bilis and H. hepaticus strains
      increased expression of MMP-7 on HT29, compared to uninfected control cells. The
      effect of MMP upregulation on HepG2, TFK-1 and HT29 was bacterial dose dependent.
      H. pylori cagA-, cagE- strain did not increase expression of MMPs. Inducible MMPs
      on colon and bile duct epithelial cells as well as hepatocytes may play an
      important role in facilitating invasion and progression of cancer by Helicobacter
      species colonizing the hepatobiliary and gastrointestinal tract.

PMID- 15866217
TI  - The humoral immuneresponse to Helicobacter pylori infection in children with
      gastrointestinal symptoms.
AB  - The prevalence of Helicobacter pylori is high in Eastern Europe. The purpose of
      this study was to estimate the prevalence of H. pylori in symptomatic Lithuanian
      children and to identify the infection by clinicopathological and serological
      analyses. One hundred sixteen symptomatic children (age 8-16) with gastritis and
      duodenal ulcer were included. Biopsies were histologically assessed according to
      the Sydney-System. Serum IgG antibodies against H. pylori were detected by an
      enzyme-linked immunosorbent assay (ELISA), using low molecular mass antigen. The
      western blot technique was used to detect serum antibodies against the cytotoxin
      associated protein (CagA) using whole cell antigen. Histologically the prevalence
      of H. pylori infection was 79% and not influenced by demographic factors. Mucosal
      inflammation and atrophy were associated with a H. pylori infection. Intestinal
      metaplasia was found in eight children, suggesting early H. pylori acquisition in
      life. Increased levels of IgG antibodies were detected in 57% of children. The
      prevalence of IgG antibodies was significantly higher in patients with duodenal
      ulcer compared to children with gastritis. Forty-four (67%) H. pylori
      seropositive children had antibodies against CagA. Low molecular weight-ELISA and
      whole cell-western blot results were significantly associated with
      histopathology, the presence of duodenal ulcer and the CagA status. A high number
      of false seronegative cases were due to poor immunological responses in children
      and poor locally validated tests. The prevalence of H. pylori infection in
      Lithuanian children is higher compared to Western Europe. The infection is
      acquired in early life. Diagnosing H. pylori infection, serology is helpful, but
      endoscopy/histology remains as gold standard.

PMID- 15866218
TI  - Restriction of DNA encoding selectable markers decreases the transformation
      efficiency of Helicobacter pylori.
AB  - Helicobacter pylori populations recovered from the human stomach display
      extensive recombination and quasispecies development, and this suggests frequent
      exchange of DNA between different strains in vivo. In vitro, however, most H.
      pylori strains display restriction to the uptake of non-self DNA, as measured
      using selectable markers, regardless of their competency for transformation with
      self DNA. We have examined the effect of different selectable markers on double
      crossover recombination efficiencies in three reference strains (1061, 26695 &
      SS1) and one clinical isolate (CHP1) of H. pylori. All strains were efficiently
      transformable to kanamycin or chloramphenicol resistance by using self-genomic
      DNA from isogenic mutants bearing the aphA3 or cat cassettes, respectively.
      However, strains 26695 and CHP1 showed a 3-5-log reduction in transformation
      efficiency by non-self recombinant DNA containing aphA3, when compared to cat.
      Strain 1061 readily accepted either cassette, and strain SS1 was poorly tolerant
      of any non-self DNA. Genome-wide random mutagenesis of these strains was only
      achievable with a selectable marker that allowed high transformation efficiency.
      Digestion of 32P-labelled cassettes by H. pylori lysates mirrored the
      transformation results and indicated that in some strains these cassettes are the
      targets of enzymatic restriction.

PMID- 15866220
TI  - The presence of the cag pathogenicity island is associated with increased
      superoxide anion radical scavenging activity by Helicobacter pylori.
AB  - Reactive oxygen species (ROS) generated by Helicobacter pylori infection have
      been suggested to be important factors in induction of gastric malignancies.
      Utilizing electron spin resonance spectrometry, H. pylori-dependent radical
      formation and hydroxyl- and superoxide-anion radical scavenging activity was
      investigated. In contrast to previous reports, we found that H. pylori does not
      produce ROS, but displays superoxide scavenging activity. This scavenging
      activity was increased in cag-positive H. pylori strains when compared to strains
      lacking an intact cag pathogenicity island, and was dependent on enzyme activity.
      We hypothesize that the increased scavenging activity of cag-positive H. pylori
      strains is an adaptation to the increased inflammatory response associated with
      the cag-positive genotype of H. pylori.

PMID- 15866219
TI  - The role of Helicobacter spp. in the pathogenesis of primary biliary cirrhosis
      and primary sclerosing cholangitis.
AB  - Helicobacter species DNA has been detected in liver tissue of patients affected
      by primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). To
      investigate a potential causative relation between Helicobacter species and
      PBC/PSC, we compared the presence of Helicobacter species-specific DNA in liver
      tissue of patients with PBC/PSC (n=18/n=13) with those of a control group of
      patients with various liver diseases with known cause (n=29). A PCR with
      Helicobacter genus-specific 16S rRNA primers was performed on DNA isolated from
      paraffin embedded liver tissue. Control patients had hepatitis-B (n=9), alcoholic
      cirrhosis (n=14), or non-cirrhotic metabolic liver disease (n=6). There was no
      significant difference between the incidence of Helicobacter spp.-specific DNA in
      PBC/PSC (9/31; 29%) and the control group (10/29; 34%). Sequence analysis
      confirmed Helicobacter spp. DNA. Because Helicobacter spp. DNA can be found in
      approximately one-third of all samples tested, it is unlikely that PSC and PBC
      are caused by Helicobacter infection.

PMID- 15866221
TI  - Gastric inflammatory markers and interleukins in patients with functional
      dyspepsia, with and without Helicobacter pylori infection.
AB  - Helicobacter pylori is the most important cause of gastritis, peptic ulcers and
      the development of gastric cancer. The chronic active inflammation is dominated
      by neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins
      (IL-8, IL-10 and IFN-gamma) are involved in the inflammatory process in the
      gastric mucosa. The aim of this study was to investigate the gastric inflammation
      in patients with functional dyspepsia. Fifty-three consecutive patients were
      included and antral biopsies were obtained for histology, culture and
      immunohistochemistry. The sections were examined for the interleukins IL-4, IL-6,
      IL-8, IL-10 and IFN-gamma as well as for the cell markers CD4, CD8, CD14, Cd19,
      CD25 and CD30. Only CD4 and CD19 were significantly increased in patients with
      increased gastric inflammation and increased density of H. pylori. However,
      several of the examined markers (IFN-gamma, IL-8, IL-10 and CD14) showed a non
      significant trend to be increased in patients with extensive gastric inflammation
      and high density of H. pylori. Therefore, an arbitrary index (IM11) for all the
      11 immunological markers was made as an average value for each of the four
      morphological groups. For the four morphologically different groups of patients
      the values were 0.49, 0.77, 0.86 and 1.25, respectively. Significant increases in
      the index from none to moderate antral inflammation as well as the density of H.
      pylori were found (p<0.001). By using an index of inflammatory markers trends can
      be summarized and thereby significant which may be of importance when gastric
      inflammation is investigated in children and patients with functional dyspepsia.

PMID- 15866222
TI  - cagA gene variants in Malaysian Helicobacter pylori strains isolated from
      patients of different ethnic groups.
AB  - Helicobacter pylori infection of a distinct subtype of cagA may lead to different
      pathological manifestation. The aim of this study is to determine the presence of
      cagA gene and its variants in H. pylori infection among different ethnic groups
      and its effect on gastroduodenal diseases. Overall detection of cagA among the
      205 clinical isolates of H. pylori was 94%. Variations in size of the 3' region
      of cagA gene were examined among 192 Malaysian H. pylori cagA-positive strains.
      Results showed that three cagA variants differing in fragment length of PCR
      products were detected and designated as type A (621-651bp), type B (732-735bp)
      and type C (525 bp). Although there was no association between any of the cagA
      subtypes with peptic ulcer disease (p>0.05), an association between cagA subtypes
      with a specific ethnic group was observed. Specific-cagA subtype A strains were
      predominantly isolated from Chinese compared to Malays and Indians (p<0.0005),
      and cagA subtype B strains were predominantly isolated from Malays and Indians
      compared to Chinese (p<0.05). The cagA type A strains of H. pylori is commonly
      found in the Chinese patients who have a higher risk of peptic ulcer disease,
      thus indicating that it could be used as an important clinical biomarker for a
      more severe infection.

PMID- 15866223
TI  - A genetic locus of Helicobacter pylori inversely associated with gastric
      intestinal metaplasia.
AB  - The genomic contents of Helicobacter pylori strain C1 from a patient with gastric
      cancer and strain 98587 from a patient with duodenal ulcer disease were compared
      using a rapid subtractive hybridisation approach. A total of 11 tester-specific
      sequences representing gene specificity, DNA rearrangement and sequence variation
      were identified. This included two novel sequences, clone P32 and clone F5, which
      have no significant homologue in the database. H. pylori strains positive for
      clone P32 were less prevalent in patients with gastric intestinal metaplasia
      (12.5%) than in duodenal ulcer (39.1%) (p=0.036), or chronic gastritis (38.1%)
      (p=0.036). The results suggest that H. pylori clone P32 is potentially a useful
      marker for distinguishing intestinal metaplasia associated strains from others.

PMID- 15866224
TI  - Trapping of growth factors by catechins: a possible therapeutical target for
      prevention of proliferative diseases.
AB  - The prevention of cancer through dietary intervention is currently receiving
      considerable attention. Several epidemiological studies substantiate that green
      tea has a protective effect against a variety of malignant proliferative
      disorders such as lung cancer, breast cancer and prostate cancer. This preventive
      potential of green tea against cancer is attributed to the biologically active
      flavonoids called catechins. Epigallocatechin 3-o-gallate, the major catechin
      found in green tea, mediates diverse physiological and pharmacological actions in
      bringing about the regression of the tumors and also lowers the risk of
      nonmalignant cardiovascular proliferative diseases. Much of the current research
      is being focused on how these catechins specifically bring about the regression
      of the experimentally induced tumors both in vitro and in vivo. These catechins
      exert diverse physiological effects against proliferative diseases by several
      mechanisms, most of which are not completely characterized. This review
      summarizes the mechanisms by which these catechins play an essential role in
      regulating the process of carcinogenesis, with a special emphasis on how these
      catechins antagonize the growth factor-induced proliferative disorders.

PMID- 15866225
TI  - Effect of postexercise carbohydrate supplementation on glucose uptake-associated
      gene expression in the human skeletal muscle.
AB  - We previously found that the exercise-induced elevation in GLUT4 mRNA of rat
      muscle can be rapidly down-regulated when glucose is given immediately following
      exercise. The purpose of this study was to determine the effect of postexercise
      carbohydrate diet on GLUT4 and hexokinase (HK) II mRNA levels in the human
      skeletal muscle. Eight untrained male subjects (age, 20.7+/-3.1 years) exercised
      for 60 min on a cycle ergometer at a 70-75% maximal oxygen consumption. The
      postexercise dietary treatment was performed in a crossover design. Immediately
      after the exercise, a diet with 70% carbohydrate content (1 g per kilogram of
      body weight; 356+/-19.8 kcal) was given to half of the subjects (eaten in 10 min)
      followed by a 3-h recovery, while the control subjects remained unfed for 3 h.
      Biopsies were performed on the deep portion of the vastus lateralis muscle of all
      subjects immediately after the exercise and 3 h after the carbohydrate ingestion.
      Blood glucose and serum insulin concentrations were measured every 30 min for 3
      h. At the end of the 3-h recovery, blood glucose and serum insulin levels were
      not different from control levels, indicating that the oral carbohydrate was
      mostly disposed in the body within 3 h. In addition, GLUT4 and HK II mRNA levels
      were significantly lowered in the exercised human skeletal muscle in subjects
      receiving the carbohydrate diet. In conclusion, the present study demonstrates
      that GLUT4 mRNA and HK II mRNA in the exercised human skeletal muscle were
      significantly lowered by a high-carbohydrate diet.

PMID- 15866226
TI  - Detection of a single nucleotide polymorphism in the human alpha-lactalbumin
      gene: implications for human milk proteins.
AB  - Variability in the protein composition of breast milk has been observed in many
      women and is believed to be due to natural variation of the human population.
      Single nucleotide polymorphisms (SNPs) are present throughout the entire human
      genome, but the impact of this variation on human milk composition and biological
      activity and infant nutrition and health is unclear. The goals of this study were
      to characterize a variant of human alpha-lactalbumin observed in milk from a
      Filipino population by determining the location of the polymorphism in the amino
      acid and genomic sequences of alpha-lactalbumin. Milk and blood samples were
      collected from 20 Filipino women, and milk samples were collected from an
      additional 450 women from nine different countries. alpha-Lactalbumin
      concentration was measured by high-performance liquid chromatography (HPLC), and
      milk samples containing the variant form of the protein were identified with both
      HPLC and mass spectrometry (MS). The molecular weight of the variant form was
      measured by MS, and the location of the polymorphism was narrowed down by protein
      reduction, alkylation and trypsin digestion. Genomic DNA was isolated from whole
      blood, and the polymorphism location and subject genotype were determined by
      amplifying the entire coding sequence of human alpha-lactalbumin by PCR, followed
      by DNA sequencing. A variant form of alpha-lactalbumin was observed in HPLC
      chromatograms, and the difference in molecular weight was determined by MS (wild
      type=14,070 Da, variant=14,056 Da). Protein reduction and digestion narrowed the
      polymorphism between the 33rd and 77th amino acid of the protein. The genetic
      polymorphism was identified as adenine to guanine, which translates to a
      substitution from isoleucine to valine at amino acid 46. The frequency of
      variation was higher in milk from China, Japan and Philippines, which suggests
      that this polymorphism is most prevalent in Asia. There are SNPs in the genome
      for human milk proteins and their implications for protein bioactivity and infant
      nutrition need to be considered.

PMID- 15866227
TI  - Tissue leptin and plasma insulin are associated with lipoprotein lipase activity
      in severely obese patients.
AB  - The development of metabolic complications of obesity has been associated with
      the existence of depot-specific differences in the biochemical properties of
      adipocytes. The aim of this study was to investigate, in severely obese men and
      women, both gender- and depot-related differences in lipoprotein lipase (LPL)
      expression and activity, as well as the involvement of endocrine and biometric
      factors and their dependence on gender and/or fat depot. Morbidly obese,
      nondiabetic, subjects (9 men and 22 women) aged 41.1+/-1.9 years, with a body
      mass index (BMI) of 54.7+/-1.7 kg/m(2) who had undergone abdominal surgery were
      studied. Both expression and activity of LPL and leptin expression were
      determined in adipose samples from subcutaneous and visceral fat depots. In both
      men and women, visceral fat showed higher LPL mRNA levels as well as lower ob
      mRNA levels and tissue leptin content than the subcutaneous one. In both
      subcutaneous and visceral adipose depots, women exhibited higher protein content,
      decreased fat cell size and lower LPL activity than men. The gender-related
      differences found in abdominal fat LPL activity could contribute to the increased
      risk for developing obesity-associated diseases shown by men, even in morbid
      obesity, in which the massive fat accumulation could mask these differences.
      Furthermore, the leptin content of fat depots as well as plasma insulin
      concentrations appear in our population as the main determinants of adipose
      tissue LPL activity, adjusted by gender, depot and BMI.

PMID- 15866228
TI  - Vitamin D receptor is required for dietary calcium-induced repression of
      calbindin-D9k expression in mice.
AB  - Calbindin (CaBP), the vitamin D-dependent calcium-binding protein, is believed to
      play an important role in intracellular calcium transport. The aim of this study
      was to investigate the effect of high dietary calcium on the expression of CaBP
      D9k and CaBP-D28k in the presence and absence of a functional vitamin D receptor
      (VDR). Treatment with the HCa-Lac diet containing 2% calcium, 1.5% phosphorus and
      20% lactose reversed the hypocalcemia seen in adult VDR-null mice in 3 weeks but
      did not significantly change the blood ionized calcium in wild-type mice. This
      dietary treatment dramatically suppressed both the duodenal and the renal CaBP
      D9k expression in wild-type mice at both mRNA and protein levels but had little
      effect on the expression of the same gene in VDR-null mice. Removal of this diet
      gradually restored the expression of CaBP-D9k to the untreated level in wild-type
      mice. Only moderate or little change in CaBP-D28k expression was seen in wild
      type and VDR-null mice fed with the HCa-Lac diet. The VDR content in the duodenum
      or kidney of wild-type mice was not altered by the dietary treatment. These
      results suggest that calcium regulates CaBP-D9k expression by modulating the
      circulating 1,25-dihydrxyvitamin D(3) level and that VDR is thus required for the
      dietary calcium-induced suppression of CaBP-D9k expression. Calcium regulation of
      the CaBP-D9k level may represent an important mechanism by which animals maintain
      their calcium balance.

PMID- 15866229
TI  - A novel assay of cell rubidium uptake using graphite furnace atomic absorption:
      application to rats on a magnesium-deficient diet.
AB  - The [Na,K]ATPase or sodium pump (SP) is a ubiquitous membrane cation transport
      system. Because of its potential participation in the pathophysiology of
      essential hypertension and cataract formation, the SP is under active
      investigation to detail its function and control. In this paper, we describe a
      novel, nonradioactive method of measuring SP ion transport activity in intact red
      blood cells (RBCs) using graphite furnace atomic absorption measurement of
      rubidium ion (Rb) uptake. This method provided sensitivity comparable to
      radioactive techniques, as assessed by experiments with human red blood cells
      (RBC) and ouabain, a known SP inhibitor, but this analytical approach eliminates
      the use of radioisotopes common to other Rb uptake assay methods. As a
      demonstration of its broader utility, the assay was used to assess the effects of
      dietary magnesium intake on SP-mediated ion transport in the RBCs of diet
      controlled rats. Rats on 7 weeks of a magnesium-deficient (MgD) diet showed
      significant reductions in serum magnesium concentration, although levels remained
      in the lower region of the reference interval for healthy, magnesium replete
      animals. Red cell Rb uptake was significantly reduced in cells from the magnesium
      restricted animals, demonstrating the sensitivity of Rb uptake to reduced
      magnesium intake, despite serum levels that fell within the reported normal
      range, and the utility of this Rb uptake assay in measuring physiological changes
      in SP function.

PMID- 15866230
TI  - Antioxidants as novel therapy in a murine model of colitis.
AB  - Reactive oxygen species (ROS) are increased in inflammatory bowel disease (IBD)
      and have been implicated as mediators of intestinal inflammation. We investigated
      the hypothesis that antioxidants with diverse properties attenuate disease
      progression in a murine dextran sodium sulfate (DSS)-induced colitis model. These
      antioxidants were (A) S-adenosylmethionine, a glutathione (GSH) precursor; (B)
      green tea polyphenols, a well-known antioxidant; and (C) 2(R,S)-n
      propylthiazolidine-4(R)-carboxylic acid (PTCA), a cysteine prodrug, involved in
      GSH biosynthesis. BALB/c mice were divided into four groups and provided with the
      above mentioned antioxidants or the vehicle incorporated into chow. The animals
      were further divided into two subgroups and given normal drinking water (control)
      or water supplemented with DSS (to induce colitis), and the progression of the
      disease was studied. DSS-treated mice developed severe colitis as shown by bloody
      diarrhea, weight loss and pathological involvement (P<.001). However, all the
      antioxidants significantly improved diarrhea and colon lesions (P<.01), and
      increased body weights (P<.05). Hematocrits were significantly less affected in
      DSS-treated animals receiving antioxidants (P<.01). Colon lengths were
      significantly decreased due to mucosal inflammation in DSS-treated animals, but
      antioxidant therapy normalized this pathological finding (P<.001). The blood
      level of reduced GSH was decreased in DSS-treated mice (P<.05) and returned to
      normal when treated with antioxidants. Serum amyloid A (acute phase protein;
      P=.0015) and tumor necrosis factor-alpha (TNF-alpha; pro-inflammatory cytokine;
      P<.01) were significantly increased in DSS-treated animals (161+/-40 pg/ml) and
      improved with antioxidant treatment (P<.01). Finally, actin cytoskeleton was
      distorted and fragmented in the mucosa of DSS-treated mice and improved with
      antioxidant therapy. In conclusion, three structurally dissimilar antioxidants
      provided protection against DSS-induced colitis in this murine model, supporting
      a possible role for antioxidant therapy in IBD patients.

PMID- 15866231
TI  - Free phytosterols facilitate excretion of endogenous cholesterol in gerbils.
AB  - To determine whether phytosterols (PST) facilitate excretion of whole body
      cholesterol and whether dietary fat or enhancing gallbladder contraction with
      curcumin might influence this process, four experiments were conducted in
      gerbils. In Experiment 1, naive gerbils received cholesterol-free purified diets
      with 30% energy from fat and 0% or 0.75% free PST from tall oil for 4 weeks. In
      Experiment 2, body cholesterol pools were expanded by feeding a diet containing
      0.3% cholesterol for 3 weeks. Subsequently, PST was provided in either fat-free
      or normal-fat diets without cholesterol for only 2 h each morning, followed by a
      low-fat diet for the rest of the day and food restriction overnight. In
      Experiment 3, gerbils were preloaded with cholesterol, followed by either PST
      alone or PST+curcumin to enhance gallbladder contraction. In Experiment 4,
      curcumin or curcumin+PST were fed with 30% as fat and 0.15% cholesterol
      throughout the study. Because of the small whole body cholesterol pool in
      Experiment 1, the impact of PST was limited. When whole body cholesterol was
      expanded in Experiments 2 and 3, subsequent reductions of liver esterified
      cholesterol by PST were significant. In the presence of dietary fat, PST caused a
      greater reduction (23%) than in a fat-free diet (8%) compared to respective
      controls. Curcumin (Experiments 3 and 4) proved ineffective in reducing liver or
      plasma cholesterol pools, and the 3:1 ratio between PST/diet cholesterol was less
      effective at blocking cholesterol absorption than a 5:1 ratio previously
      employed. Thus, free PST removed whole body cholesterol, which was enhanced by
      concomitant fat intake, but was unaffected by a gallbladder contracting agent.

PMID- 15866232
TI  - Diabetes and dietary copper alter 67Cu metabolism and oxidant defense in the rat.
AB  - Perturbations in copper (Cu) metabolism are a characteristic of diabetes, for
      example, elevated plasma Cu and compromised oxidant defense related to diabetes
      induced effects on Cu-containing enzymes. Herein, the redistribution of Cu in
      selected tissues is described in response to diabetic and nondiabetic states in
      rats that were fed diets adequate in (12 mg Cu/kg of diet) or deficient in (no
      added Cu) Cu. Diabetes was induced by intravenous administration of
      streptozotocin (40 mg/kg body weight). After 5 weeks, rats were gavaged with
      (67)Cu (0.74 MBq per rat) using the Cu-deficient diet as a vehicle (suspended 1:3
      in water) and killed at various time points. The use of (67)Cu allowed for the
      assessment of short-term Cu distribution and its comparison to the steady-state
      Cu distribution, as determined by direct Cu analysis. In contrast to control
      rats, the adaptive mechanisms for Cu homeostasis in diabetic rats were impaired.
      In general, measures of Cu retention were reduced in diabetic rats compared to
      corresponding values for control rats. Moreover, diabetic rats had low copper,
      zinc superoxide dismutase activity that was reduced even further when diabetic
      rats were fed with low-Cu diets. However, liver and kidney metallothionein and
      plasma ceruloplasmin levels were elevated in diabetic rats compared to control
      rats. Such diabetes-related metabolic alterations were taken as measures of
      increased oxidative stress and inflammation, which may have implications in the
      progression of diabetes-related pathologies.

PMID- 15866233
TI  - Mast cells and endothelin-1: a life-saving biological liaison?
AB  - Over a decade ago endothelin-1 (ET-1) was described as belonging to the
      assortment of mast cell-derived and mast cell-bound cytokines. Mast cell subtype-
      and environment-dependent, ET-1 acts as a potent non-immunological mast-cell
      activator, which leads to degranulation and mediator release. The biological
      significance of this phenomenon remained obscure; however, a recent report sheds
      new light on this delicate mast cell-ET-1 connection. The authors of this report
      use mast cell-deficient mice to provide convincing evidence that mast cells
      counteract the toxicity induced by high concentrations of ET-1, and thereby
      promote homeostasis.

PMID- 15866234
TI  - Is RNA interference feasible for the control of foot-and-mouth disease outbreaks?

PMID- 15866236
TI  - Effector lymphoid tissue and its crucial role in protective immunity.
AB  - It is often argued that T cell-mediated immunity to secondary infection is
      dependent on the 'accelerated' responses of memory T cells in lymph nodes.
      However, new evidence points to a crucial role for effector memory T cells, which
      are resident in peripheral tissues, in immune protection. These T cells, which
      reside in peripheral tissues, are not necessarily bound by an anatomical
      structure and can be present at many sites. Collectively, they represent a third
      functional tissue of the immune system, uniquely specialized to mediate
      protective immunity. We propose that the paradigm 'effector lymphoid tissue'
      needs to be articulated and developed as a focus of new research to describe and
      understand the unique role this tissue has in protective immunity.

PMID- 15866237
TI  - Beneficial autoimmunity in Type 1 diabetes mellitus.
AB  - The trigger that leads to the pathogenesis of type 1 diabetes is currently
      unknown. It is well established that the pathophysiology of the disease is
      biphasic. In the first stage, leukocytes infiltrate the pancreatic islets in a
      response that does not cause damage. In the second phase, which occurs only in
      diabetes-prone individuals and strains, autoreactive T cells acquire aggressive
      potential and destroy the majority of the pancreatic islets. Rodents and humans
      exhibit a physiological ripple of apoptotic beta-cell death shortly after birth,
      which induces an adaptive autoimmune response towards islet-antigens, both in
      diabetes-prone non-obese diabetic (NOD) mice and in mice that do not develop
      diabetes. Here, we propose that the early T cell-mediated autoimmune response
      towards islet-antigens is physiological, purposeful and beneficial.

PMID- 15866238
TI  - Unveiling the enigma of the CNS as a B-cell fostering environment.
AB  - This Opinion deals with the apparent paradox between the 'immune privileged'
      status of the central nervous system (CNS) and its propensity to act as a B-cell
      fostering environment in a variety of neurological disorders. Evidence will be
      reviewed that: (i) molecules regulating B-cell homing and survival are produced
      in the CNS, (ii) in different neuroinflammatory diseases, B cells can undergo a
      local recapitulation of the differentiation occurring in secondary lymphoid
      organs and (iii) ectopic lymphoid follicles develop in the meninges of multiple
      sclerosis (MS) patients.

PMID- 15866239
TI  - Induction, exacerbation and inhibition of allergic and autoimmune diseases by
      infection.
AB  - Epidemiological and experimental data suggest that infections or the exposure to
      non-pathogenic bacteria protect individuals from developing some autoimmune and
      atopic disorders. Generally, these findings support the 'hygiene hypothesis',
      which attributes the rise in autoimmune and atopic disorders to a lack of
      infections that normally keep the immune system balanced by inducing
      immunoregulation. The suspected key players for infection-mediated immune
      suppression of autoimmunity and atopy are T regulatory cells and dendritic cells,
      which produce immunosuppressive cytokines, such as interleukin-10 and
      transforming growth factor-beta. However, there is also solid evidence suggesting
      that infections can exacerbate or even directly cause autoimmune and allergic
      disorders. In this Review, we discuss which type of infections induce, exacerbate
      or inhibit allergic and autoimmune diseases and point at infection-induced
      immunological mechanisms influencing the development of autoimmunity and atopy.

PMID- 15866240
TI  - Multi-faceted strategies to combat disease by interference with the chemokine
      system.
AB  - Inappropriate cell recruitment is a hallmark of all autoimmune, allergic and
      inflammatory diseases. The prevention of inflammation by interfering with
      cellular recruitment through the neutralization of cytokines and adhesion
      molecules has proven to be successful in the clinic. Chemokines are important
      potential targets owing to their central role in the cell recruitment process.
      Chemokines are unique among cytokines because they signal through seven
      transmembrane receptors, thus enabling the identification of small molecule
      inhibitors through high throughput screening. The object of this Review is to
      discuss the validity and feasibility of targeting several points of therapeutic
      intervention offered by the chemokine system and to assess the state of play
      within the field to date.

PMID- 15866241
TI  - Humoral autoimmunity against endothelium: theory or reality?
AB  - Despite the discovery of anti-endothelial cell antibodies (AECA) in a
      heterogeneous group of disorders characterized by endothelial damage, their
      pathogenic role is still debated. Experimental in vitro models indicate that they
      can either damage endothelial cells or trigger cell signaling by reacting with as
      yet undefined surface molecules. However, clinical studies suggest that, in
      addition to AECA, other pathogenic mechanisms are involved in the vasculitic
      process. Recently, antibodies specific for beta2 glycoprotein I, the phospholipid
      binding protein targeted by anti-phospholipid antibodies, have been shown to
      display anti-endothelial activity. These autoantibodies recognize beta2
      glycoprotein I adhered to the endothelium and induce a cell perturbation that
      might underlie the thrombophilic state of the anti-phospholipid syndrome.

PMID- 15866242
TI  - CD1 and MHC II find different means to the same end.
AB  - CD1 molecules are a third family of antigen-presenting molecules and are the only
      one specialized to present lipid-containing antigens. Some CD1 molecules traffic
      to the same intracellular compartments as MHC II molecules. Moreover, MHC II and
      the class II-associated invariant chain influence CD1d trafficking. Despite this
      intersection between the MHC II and CD1 pathways, CD1 proteins use a mechanism
      entirely different from MHC II to traffic to late endosomes to acquire antigens.
      Recent experimental evidence has illuminated these unique aspects of the CD1
      antigen-presentation pathway.

PMID- 15866243
TI  - PA catheter-guided therapy does not benefit critically ill patients.

PMID- 15866244
TI  - Shoulder impingement syndrome.
AB  - Subacromial impingement syndrome is a common cause of shoulder pain. The purpose
      of this article is to review the clinical presentation, physical examination
      findings, and differential diagnosis of impingement syndrome. Using an evidence
      based approach, we propose an algorithm for the management of subacromial
      impingement syndrome including indications for nonoperative management, advanced
      imaging, and operative management.

PMID- 15866245
TI  - Quantitative assessment of thrombus burden predicts the outcome of treatment for
      venous thrombosis: a systematic review.
AB  - PURPOSE: Clot-burden change in patients receiving anticoagulant therapy, by
      predicting subsequent recurrent venous thromboembolism, may provide a clinically
      relevant surrogate endpoint of prognostic importance. The validity of this
      objective measure is yet to be established. METHODS: A PubMed search was
      performed to retrieve articles published up to December 2003. We identified 11
      randomized trials reported from 1990 to 2003 that met our study identification
      and selection criteria. Anticoagulant therapy subsequently approved by regulatory
      affairs was assessed by clot-burden change and the validated outcome measure,
      long-term venous thromboembolism. Two additional randomized trials, partly
      meeting the inclusion criteria, were included in the sensitivity analysis.
      RESULTS: Individual studies suggested a predictive relationship between clot
      burden change and likelihood of recurrent venous thromboembolism irrespective of
      the particular anticoagulant. The summary treatment effects strongly favored the
      therapy under evaluation and were in harmony for improved clot-burden (relative
      risk 0.82; 95% CI, 0.76-0.88; P <0.001) and for recurrent venous thromboembolism
      (relative risk 0.56; 95% CI, 0.42-0.76; P <0.001). The aggregate data show a
      striking predictive correlation for clot-burden change and subsequent recurrent
      venous thromboembolism using meta-regression analysis; (correlation = 0.81, P =
      0.005) validating quantitative clot-burden assessment. CONCLUSION: Clot-burden
      change predicts long-term outcome, providing clinically relevant, patient
      specific prognostic findings that may guide duration of anticoagulant therapy as
      well as provide a valid surrogate endpoint for clinical trials of innovative
      antithrombotic therapy, allowing more efficient trials exposing far fewer
      patients to the hazards of ineffective therapy than is required for outcome
      studies. Noninvasive assessment (duplex ultrasonography) of clot-burden change is
      currently being deployed for use in clinical trials.

PMID- 15866246
TI  - How should patients with unstable angina and non-ST-segment elevation myocardial
      infarction be managed? A meta-analysis of randomized trials.
AB  - PURPOSE: Patients with unstable angina or non-ST-segment elevation myocardial
      infarction (MI) may be managed with either an "invasive" or "conservative"
      strategy. It is unclear which of these strategies is superior. METHODS: We
      identified studies with MEDLINE and EMBASE searches (1966-September 2003) and by
      reviewing reference lists. Studies were included if they were randomized
      controlled trials comparing management strategies for patients in the early post
      unstable angina/non-ST-segment elevation MI period and had follow-up data for at
      least 3 months. RESULTS: Seven trials that randomized a total of 9212 patients
      were included. The pooled odds ratio (OR) for all-cause mortality was 0.96 (95%
      confidence interval [CI]: 0.72 to 1.27). The occurrence of fatal or nonfatal re
      infarction was reduced with an invasive strategy (OR 0.73; 95% CI: 0.61 to 0.88)
      as was readmission to hospital (OR 0.67; 95% CI: 0.48 to 0.94). The endpoints of
      nonfatal MI and the composite of death or nonfatal MI showed nonsignificant
      trends favoring an invasive strategy. Trials that included a higher proportion of
      patients with ST-segment depression on admission and trials in which a larger
      proportion of patients underwent revascularization showed a greater magnitude of
      benefit for an invasive strategy. CONCLUSION: For patients with unstable
      angina/non-ST-segment elevation MI, an invasive strategy reduces rates of fatal
      or nonfatal re-infarction and hospital readmission, but not all-cause mortality,
      when compared with a noninvasive strategy. These results suggest that an invasive
      management strategy should be considered for all patients with unstable
      angina/non-ST-segment elevation MI and perhaps in particular those with ST
      segment depression.

PMID- 15866247
TI  - Rapid resolution of a common problem.

PMID- 15866248
TI  - An unexpected finding.

PMID- 15866249
TI  - Moving to a slow beat.

PMID- 15866250
TI  - Pulmonary artery catheterization in acute coronary syndromes: insights from the
      GUSTO IIb and GUSTO III trials.
AB  - PURPOSE: To correlate pulmonary artery catheterization (PAC) use and 30-day
      outcomes and to characterize the use of pulmonary artery catheters among patients
      with acute coronary syndromes (ACS). SUBJECTS AND METHODS: We retrospectively
      studied 26437 ACS patients from two large multicenter, international randomized
      clinical trials. Multivariable and causal inference analyses were applied to
      adjust for differences in baseline risk. RESULTS: PAC was performed in 735
      patients (2.8%), with a median time to insertion of 24 hours. Patients undergoing
      PAC were older (median, 67 vs. 64 years), more often diabetic (25.7% vs.16.2%),
      and more likely to present with ST-segment elevation (81.6% vs. 70.2%) or Killip
      class III or IV (7.9% vs. 1.4%). US patients were 3.8 times more likely than non
      US patients to undergo PAC. Patients managed with PAC also underwent more
      procedures, including percutaneous intervention (40.7% vs. 18.1%), coronary
      artery bypass grafting (12.5% vs. 7.7%), and endotracheal intubation (29.3% vs.
      2.2%). Mortality at 30 days was substantially higher among patients with PAC for
      both unadjusted (odds ratio [OR] 8.7; 95% confidence interval [CI] 7.3-10.2) and
      adjusted analyses (OR 6.4; 95% CI 5.4-7.6) in all groups except in patients with
      cardiogenic shock (OR 0.99; 95% CI 0.80-1.23). CONCLUSIONS: PAC was associated
      with increased mortality, both before and after adjustment for baseline patient
      differences and subsequent events that may have led to PAC use, except in
      patients with cardiogenic shock. The definitive role of PAC in managing patients
      with ACS is still to be determined.

PMID- 15866251
TI  - Overweight and obesity as risk factors for atrial fibrillation or flutter: the
      Danish Diet, Cancer, and Health Study.
AB  - PURPOSE: We examined the association between the body mass index analyzed as a
      continuous variable and by categorization according to World Health Organization
      criteria (normal weight, overweight and obesity) and the risk of a hospital
      (inpatient as well as outpatient) diagnosis of atrial fibrillation or flutter.
      METHODS: Population-based prospective cohort study conducted from December 1993
      to December 2001 among 47589 participants (22482 men and 25107 women) without
      preexisting cardiovascular or endocrine disease and with a mean age at baseline
      of 56 years (range 50-64 years) in the Danish Diet, Cancer, and Health Study.
      Subjects were followed up in the Danish National Registry of Patients and in the
      Danish Civil Registration System. RESULTS: During follow-up (mean, 5.7 years)
      atrial fibrillation or flutter developed in 553 subjects (372 men and 181 women).
      The adjusted hazard ratio for atrial fibrillation or flutter per unit of increase
      in the body mass index was 1.08 (95% confidence interval [CI]: 1.05 to 1.11) in
      men and 1.06 (95% CI: 1.03 to 1.09) in women. When using normal weight as a
      reference, the adjusted hazard ratio for atrial fibrillation or flutter by
      overweight was 1.75 (95% CI: 1.35 to 2.27) in men and 1.39 (95% CI: 0.99 to 1.94)
      in women. The adjusted hazard ratio by obesity was 2.35 (95% CI: 1.70 to 3.25) in
      men and 1.99 (95% CI: 1.31 to 3.02) in women. CONCLUSION: Overweight and obesity
      are associated with an increased risk of a diagnosis of atrial fibrillation or
      flutter.

PMID- 15866252
TI  - Correlates of cognitive impairment among patients with heart failure: results of
      a multicenter survey.
AB  - PURPOSE: Cognitive impairment is an exceedingly prevalent condition among
      patients with heart failure, independently associated with disability and
      mortality. However, the determinants of cognitive dysfunction associated with
      heart failure are still unclear. We assessed the correlates of cognitive
      impairment among patients with heart failure enrolled in a multicenter
      pharmacoepidemiology survey. METHODS: The association with cognition of
      demographic characteristics, objective tests and measures, medications, and
      comorbid conditions was assessed in 1511 patients with heart failure who had been
      admitted to 81 hospitals throughout Italy. Cognitive impairment was defined by a
      Hodkinson Abbreviated Mental Test score < 7. RESULTS: According to multivariate
      logistic regression modeling, age (per each decade: OR = 2.01; 95% confidence
      interval [CI] 1.72-2.35), the comorbidity score (OR 1.11; 95% CI 1.03-1.20),
      education (OR 0.88; 95% CI 0.84-0.2), low serum albumin (OR 1.78; 95% CI 1.35
      2.34), sodium (OR 1.56; 95% CI 1.06-2.29), and potassium levels (OR 1.58; 95% CI
      1.09-2.29), hyperglycemia (OR 1.33; 95% CI 1.02-1.73), anemia (OR 1.38; 95% CI
      1.09-1.75), and systolic blood pressure levels > or = 130 mm Hg (OR 0.60; 95% CI
      0.37-0.97) were independently associated with cognitive impairment, after
      adjusting for potential confounders. Among participants with abnormal laboratory
      findings on admission, restoration of normal glucose, potassium, and hemoglobin
      levels during hospital stay was associated with improved cognitive performance at
      discharge. CONCLUSIONS: Cognitive impairment among patients with heart failure is
      associated with several comorbid conditions, some of which are potentially
      treatable. This highlights the key role of comprehensive approach to the
      assessment and treatment of patients with heart failure.

PMID- 15866253
TI  - Cost-effectiveness of prophylactic low molecular weight heparin in pregnant women
      with a prior history of venous thromboembolism.
AB  - PURPOSE: Women with a history of prior venous thromboembolism have an increased
      risk for recurrence during pregnancy. Although thromboprophylaxis reduces this
      risk, recent evidence suggests that, in many cases, prophylaxis can be safely
      withheld because the estimated recurrence risk is very low. The balance of risks
      and benefits in women with different recurrence risks has not been examined.
      METHODS: We developed a Markov state transition decision analytic model to
      compare prophylactic low molecular weight heparin to expectant management for
      pregnant women with a single prior venous thromboembolism. A lifetime time
      horizon and societal perspective were assumed. Input data were obtained by
      literature review. Outcomes were expressed as U.S. dollars per quality-adjusted
      life-year (QALY). RESULTS: For "low-risk" women with a prior venous
      thromboembolism associated with a transient risk factor and no known
      thrombophilic condition (recurrence risk 0.5%), expectant management was both
      more effective and less costly than prophylaxis. For "high-risk" women with prior
      idiopathic venous thromboembolism or known thrombophilic condition (recurrence
      risk 5.9%), prophylaxis was associated with a reasonable cost-effectiveness ratio
      (USD 38,700 per QALY) given a risk of bleeding complications <1.0% (base case
      0.5%). CONCLUSION: For low-risk women with prior venous thromboembolism,
      expectant management during pregnancy leads to better outcomes than
      administration of prophylactic low molecular weight heparin. For high-risk women,
      antepartum thromboprophylaxis is a cost-effective use of resources.

PMID- 15866254
TI  - Infliximab therapy in established rheumatoid arthritis: an observational study.
AB  - PURPOSE: To investigate the efficacy, toxicity and drug discontinuation rate in
      an observational study of patients with established rheumatoid arthritis treated
      with infliximab. SUBJECTS AND METHODS: Between September 1999 and June 2003, we
      enrolled 84 patients with rheumatoid arthritis who were being treated with
      infliximab. All patients met the American College of Rheumatology criteria for
      rheumatoid arthritis and had been refractory to (or did not tolerate) at least
      two disease-modifying antirheumatic drugs. Patients entering the study had a
      negative purified protein derivative skin test, were fully informed about the
      treatment regimen, and were followed up at predefined times according to a
      standardized protocol. Data concerning infliximab dosage, tolerability, adverse
      events, concomitant therapy, dosage interval, and drug discontinuation were all
      recorded. In addition, the clinical and laboratory variables according to the
      American College of Rheumatology 20% and 50% response criteria and the disease
      activity score for the 28 joint indices were also recorded. RESULTS: There were
      61 women and 23 men with a mean age of 59 +/- 8 years and mean disease duration
      of 11 +/- 6 years. Seventy-five percent (63/84) were seropositive for IgM
      rheumatoid factor. After the first year of treatment, 84.5% of patients continued
      to be treated with infliximab, whereas this percentage was 73% after the second
      year and 59% after the third year of treatment. The American College of
      Rheumatology 20% response criteria was met by 59/84 (70%) of patients, and 38/84
      (45%) of the patients achieved the 50% response criteria in the first year of
      treatment. At the second year of therapy, the American College of Rheumatology
      20% response criteria were reached by 35/84 (42%) of the patients and the 50%
      response criteria by 27/84 (32%). At the third year of treatment with infliximab,
      the American College of Rheumatology 20% and 50% response criteria were achieved
      by 13/84 (15.5%) and 10/84 (12%) of the patients, respectively. Twenty-eight of
      eighty-four (33%) patients discontinued infliximab therapy. The risk of drug
      discontinuation decreased with the concomitant use of methotrexate. The main
      reasons for drug discontinuation were adverse drug reactions (16/84, 19%),
      followed by lack of efficacy (9/84, 11%). The main reasons for drug
      discontinuation due to side effects were immediate hypersensitivity reactions
      (9/84, 11%) and infections (6/84, 7%). CONCLUSION: Infliximab was found to be an
      alternative treatment with a relatively acceptable toxicity profile, despite the
      fact that two patients developed pulmonary tuberculosis. After the third year of
      therapy, 59% of patients continued to be treated with infliximab. The concomitant
      use of methotrexate was associated with the continuation of infliximab therapy.

PMID- 15866255
TI  - Group versus individual academic detailing to improve the use of antihypertensive
      medications in primary care: a cluster-randomized controlled trial.
AB  - PURPOSE: To compare group versus individual academic detailing to increase
      diuretic or beta-blocker use in hypertension. METHODS: We conducted a cluster
      randomized controlled trial in a large health maintenance organization. Subjects
      (N=9820) were patients with newly treated hypertension in the year preceding the
      intervention (N=3692), the 9 months following the intervention (N=3556), and the
      second year following intervention (N=2572). We randomly allocated 3 practice
      sites to group detailing (N=227 prescribers), 3 to individual detailing (N=235
      prescribers), and 3 to usual care (N=319 prescribers). Individual detailing
      entailed a physician-educator meeting individually with clinicians to address
      barriers to prescribing guideline-recommended medications. The group detailing
      intervention incorporated the same social marketing principles in small groups of
      clinicians. RESULTS: In the first year following the intervention, the rates of
      diuretic or beta-blocker use increased by 13.2% in the group detailing practices,
      12.5% in the individual detailing practices, and 6.2% in the usual care
      practices. As compared with usual care practices, diuretic or beta-blocker use
      was more likely in group detailing practices (adjusted odds ratio (OR), 1.40; 95%
      confidence interval (CI), 1.11 - 1.76) and individual detailing practices
      (adjusted OR, 1.30; 95% CI, 0.95 - 1.79). Neither intervention affected blood
      pressure control. Two years following this single-visit intervention, there was
      still a trend suggesting a persistent effect of individual (OR, 1.22; 95% CI,
      0.92 - 1.62), but not group, detailing (OR, 1.06; 95% CI, 0.80 - 1.39), as
      compared with usual care. CONCLUSION: Both group and individual academic
      detailing improved antihypertensive prescribing over and above usual care but may
      require reinforcement to sustain improvements.

PMID- 15866256
TI  - Is hospital service associated with racial and ethnic disparities in experiences
      with hospital care?
AB  - PURPOSE: Little is known about the influence of processes of hospital care on
      racial and ethnic differences in experiences with hospital care. SUBJECTS AND
      METHODS: To determine whether patient experiences differed by race and ethnicity
      and whether these differences were associated with hospital care characteristics,
      we analyzed survey and hospital administrative data from 2664 adult patients
      after hospitalization at an urban teaching hospital during 1998-1999. We assessed
      the association of patient race and ethnicity with reporting problems in multiple
      dimensions of patient experience, using logistic regression to adjust for sex,
      age, self-reported health status, insurance status, income, route of hospital
      admission, and hospital service. We then stratified adjusted analyses by hospital
      service. RESULTS: After adjustment for demographic and hospital characteristics,
      black (odds ratio (OR): 1.8; 95% confidence interval [CI]: 1.3-2.6) and Latino
      (OR: 2.0; 95% CI: 1.3-3.0) patients reported more problems with respect for their
      preferences compared to whites. Blacks reported more problems with respect for
      their preferences (OR: 1.7; 95% CI: 1.0-3.0) among patients discharged from
      surgical services, and Latinos reported more problems with respect for their
      preferences (OR:3.6; CI: 1.6-8.2) among patients discharged from obstetrical
      services when compared to whites. Patient experiences did not significantly
      differ by race among patients discharged from medical services. CONCLUSIONS: We
      found significant racial and ethnic differences in patients' experiences with
      hospital care, particularly in respect for patient preferences. Our findings
      suggest physicians and hospital staff should strive to understand and address the
      expectations of black and Latino patients, particularly those who are
      hospitalized for surgical or obstetrical issues.

PMID- 15866257
TI  - A comparison of two hospitalist models with traditional care in a community
      teaching hospital.
AB  - PURPOSE: Many studies have documented significant length of stay reduction and
      cost savings when hospitalist care is compared with traditional care. However,
      less is known about the concurrent performance of more than one hospitalist model
      in a single site. SUBJECTS AND METHODS: This retrospective cohort study of 10595
      patients was conducted between July 2001 and June 2002 in a tertiary care
      community-based teaching hospital. Risk-adjusted length of stay, variable costs,
      30-day readmission rates, and in-hospital and 30-day mortality were measured for
      patients treated by Community Physicians, Private Hospitalists and Academic
      Hospitalists. RESULTS: There was a 20% reduction in length of stay on the
      Academic Hospitalist service (p <.0001) and 8% on the Private Hospitalist service
      (P = .049) compared with Community Physicians. Similarly, total costs were 10%
      less on the Academic (P <.0001) and 6% less on the Private Hospitalist (P = .02)
      services compared with Community Physicians. The length of stay of Academic
      Hospitalists was 13% shorter than that of Private Hospitalists (P = .002);
      differences in costs between hospitalist groups were not statistically
      significant. Differences in in-hospital and 30-day mortality and 30-day
      readmission rates among the 3 physician groups were also not statistically
      significant. CONCLUSIONS: The impact on patient outcomes and resource utilization
      may vary with the hospitalist model used. Future studies should examine the
      specific organizational characteristics of hospitalists that contribute to
      improved patient care and resource utilization.

PMID- 15866258
TI  - Incidence and prognosis of acute heart failure in the thrombotic
      microangiopathies.

PMID- 15866259
TI  - Anemia and ischemia: myocardial injury in patients with gastrointestinal
      bleeding.

PMID- 15866260
TI  - Treatment of rheumatic inflammatory disease in 25 patients with secondary
      amyloidosis using tumor necrosis factor alpha antagonists.

PMID- 15866261
TI  - Estimating the cost to departments of medicine of training residents and fellows:
      a collaborative analysis.

PMID- 15866263
TI  - Is life expectancy of polycythemia vera patients clearly different from that of
      the general population?

PMID- 15866264
TI  - Regarding the Lakkireddy et al article on death certificate completion.

PMID- 15866265
TI  - Age-adjusted survival gained by treatment: an alternative way of presenting
      survival.

PMID- 15866266
TI  - Business and research.

PMID- 15866267
TI  - Sources, occurrence, trends and pathways of contaminants in the arctic physical
      environment: introduction to the special issue.

PMID- 15866268
TI  - Recent climate change in the Arctic and its impact on contaminant pathways and
      interpretation of temporal trend data.
AB  - The Arctic has undergone dramatic change during the past decade. The observed
      changes include atmospheric sea-level pressure, wind fields, sea-ice drift, ice
      cover, length of melt season, change in precipitation patterns, change in
      hydrology and change in ocean currents and watermass distribution. It is likely
      that these primary changes have altered the carbon cycle and biological systems,
      but the difficulty of observing these together with sporadic, incomplete time
      series makes it difficult to evaluate what the changes have been. Because
      contaminants enter global systems and transport through air and water, the
      changes listed above will clearly alter contaminant pathways. Here, we review
      what is known about recent changes using the Arctic Oscillation as a proxy to
      help us understand the forms under which global change will be manifest in the
      Arctic. For Pb, Cd and Zn, the Arctic is likely to become a more effective trap
      because precipitation is likely to increase. In the case of Cd, the natural cycle
      in the ocean appears to have a much greater potential to alter exposure than do
      human releases of this metal. Mercury has an especially complex cycle in the
      Arctic including a unique scavenging process (mercury depletion events),
      biomagnifying foodwebs, and chemical transformations such as methylation. The
      observation that mercury seems to be increasing in a number of aquatic species
      whereas atmospheric gaseous mercury shows little sign of change suggests that
      factors related to change in the physical system (ice cover, permafrost
      degradation, organic carbon cycling) may be more important than human activities.
      Organochlorine contaminants offer a surprising array of possibilities for changed
      pathways. To change in precipitation patterns can be added change in ice cover
      (air-water exchange), change in food webs either from the top down or from the
      bottom up (biomagnification), change in the organic carbon cycle and change in
      diets. Perhaps the most interesting possibility, presently difficult to predict,
      is combination of immune suppression together with expanding ranges of disease
      vectors. Finally, biotransport through migratory species is exceptionally
      vulnerable to changes in migration strength or in migration pathway-in the
      Arctic, change in the distribution of ice and temperature may already have caused
      such changes. Hydrocarbons, which tend to impact surfaces, will be mostly
      affected by change in the ice climate (distribution and drift tracks). Perhaps
      the most dramatic changes will occur because our view of the Arctic Ocean will
      change as it becomes more amenable to transport, tourism and mineral exploration
      on the shelves. Radionuclides have tended not to produce a radiological problem
      in the Arctic; nevertheless one pathway, the ice, remains a risk because it can
      accrue, concentrate and transport radio-contaminated sediments. This pathway is
      sensitive to where ice is produced, what the transport pathways of ice are, and
      where ice is finally melted-all strong candidates for change during the coming
      century. The changes that have already occurred in the Arctic and those that are
      projected to occur have an effect on contaminant time series including direct
      measurements (air, water, biota) or proxies (sediment cores, ice cores, archive
      material). Although these 'system' changes can alter the flux and concentrations
      at given sites in a number of obvious ways, they have been all but ignored in the
      interpretation of such time series. To understand properly what trends mean,
      especially in complex 'recorders' such as seals, walrus and polar bears, demands
      a more thorough approach to time series by collecting data in a number of media
      coherently. Presently, a major reservoir for contaminants and the one most
      directly connected to biological uptake in species at greatest risk-the ocean
      practically lacks such time series.

PMID- 15866269
TI  - Sources and pathways of selected organochlorine pesticides to the Arctic and the
      effect of pathway divergence on HCH trends in biota: a review.
AB  - Historical global usage and emissions for organochlorine pesticides (OCPs),
      including hexachlorocyclohexanes (HCHs), dichlorodiphenyltrichloroethane (DDT),
      toxaphene and endosulfan, are presented. Relationships between the air
      concentrations of these OCPs and their global emissions are also discussed.
      Differences between the pathways of alpha- and beta-HCH to the Arctic Ocean are
      described in the context of environmental concentrating and diluting processes.
      These concentrating and diluting processes are shown to control the temporal and
      spatial loading of northern oceans and that the HCH burdens in marine biota from
      these oceans respond accordingly. The HCHs provide an elegant example of how
      hemispheric-scale solvent switching processes can alter the ocean into which an
      HCH congener partitions, how air-water partitioning controls the pathway for HCHs
      entering the Arctic, and how the various pathways impact spatial and temporal
      trends of HCH residues in arctic animals feeding out of marine and terrestrial
      foodwebs.

PMID- 15866270
TI  - The relative influence of distant and local (DEW-line) PCB sources in the
      Canadian Arctic.
AB  - Soil PCB contamination has been delineated at 18 of 21 Distant Early Warning Line
      (DEW-line) stations being cleaned up by the Canadian Department of National
      Defence (DND). As a result, detailed surface soil delineation data has been
      reported for contamination exceeding 1 microg/g (dw total Aroclor), which is the
      remedial criteria for PCB contaminated soil under the DEW-line cleanup project.
      The results of this delineation work has allowed us to estimate the mass of PCB
      contained in surface soil at these sites and to quantify the DEW-line as a source
      of PCBs to both local and Arctic wide contamination. Our analysis of DEW-line
      cleanup delineation reports suggests that pre-cleanup surface soils (top 10 cm)
      with over 1 microg/g PCB constituted a source of PCBs that ranged from 0.8 to 43
      kg with a mean of 18 kg. The total mass of PCB at all 18 sites was 119 kg.
      Previous studies have described a "halo-effect" that surrounds DEW-line sites,
      whereby PCB signatures in soil and plants up to 10 km from source areas were
      attributed to the local source. At Cambridge Bay (CAM-M), Nunavut, our inventory
      of PCB sources and redistribution suggests that up to 3.4 kg of PCB were exported
      from the site to the surrounding tundra prior to cleanup. The primary mechanism
      of transportation appears to be wind borne particulate. Potential vapour phase
      emissions of PCB from contaminated soil at DEW-line sites appears to have been
      negligible.

PMID- 15866271
TI  - Temporal and spatial variabilities of atmospheric polychlorinated biphenyls
      (PCBs), organochlorine (OC) pesticides and polycyclic aromatic hydrocarbons
      (PAHs) in the Canadian Arctic: results from a decade of monitoring.
AB  - The Northern Contaminants Program (NCP) baseline monitoring project was
      established in 1992 to monitor for persistent organic pollutants (POPs) in Arctic
      air. Under this project, weekly samples of air were collected at four Canadian
      and two Russian arctic sites, namely Alert, Nunavut; Tagish, Yukon; Little Fox
      Lake, Yukon; Kinngait, Nunavut; Dunai Island, Russia and Amderma, Russia.
      Selected POPs, including polycyclic aromatic hydrocarbons (PAHs), polychlorinated
      biphenyls (PCBs) and organochlorine (OC) pesticides, were analyzed in both the
      gas and particulate phases. This paper summarizes results obtained from this
      project in the past 5 years. Temporal trends were developed for atmospheric PCBs
      and OCs observed at Alert using a digital filtration (DF) technique. It was found
      that trends developed with 5 years of data (1993-1997) did not differ
      significantly from those determined with 7 years of data (1993-1999). This
      implies that with the DF technique, long-term trends can still be developed with
      less than 10 years of data. An acceleration in decline of OC and PCB air
      concentrations was noted in 1999 for some compounds, although the reason is
      unknown. Monitoring efforts must continue to assess the effect of this decline on
      the long-term trends of POPs in the Canadian Arctic. Occasional high trans-/cis
      chlordane ratios and heptachlor air concentrations measured at Alert between 1995
      and 1997 suggests sporadic fresh usage of chlordane-based pesticides. However,
      significant decreasing trends of chlordanes along with their chemical signatures
      has provided evidence that emission of old soil residues is replacing new usage
      as an important source to the atmosphere. Measurements of OC air concentrations
      conducted at Kinngait in 1994-1995 and 2000-2001 indicated faster OC removal at
      this location than at Alert. This may be attributed to the proximity of Kinngait
      to temperate regions where both biotic and abiotic degradation rates are faster.
      The PAH concentrations observed at Alert mimic those at mid-latitudes and are
      consistent with long-range transport to the Arctic, particularly for the lighter
      PAHs. A decline in particulate PAH was observed, similar to atmospheric sulphate
      aerosol and can be attributed to the collapse of industrial activity in the
      former Soviet Union between 1991 and 1995. Spatial comparisons of OC seasonality
      at Alert, Tagish, Dunai and Kinngait show elevated air concentrations of some
      compounds in spring. However, elevated spring concentrations were observed for
      different compounds at different sites. Potential causes are discussed. Further
      investigation in the atmospheric flow pattern in spring which is responsible for
      the transport of POPs into the Arctic is required. OC and PCB air concentrations
      at Alert were found to be influenced by two climate variation patterns, the North
      Atlantic Oscillation (NAO) and the Pacific North American (PNA) pattern.
      Planetary atmospheric patterns must be taken into account in the global
      prediction and modelling of POPs in the future.

PMID- 15866272
TI  - Polychlorinated naphthalenes in air and snow in the Norwegian Arctic: a local
      source or an Eastern Arctic phenomenon?
AB  - PCNs were measured in air and snow during separate field campaigns at Ny-Alesund
      (April 2001) and Tromso (February/March 2003) in the Norwegian Arctic. Air
      concentrations ranged from 27 to 48 and 9 to 47 pg sigmaPCN m(-3) for Ny-Alesund
      (n=6) and Tromso (n=10), respectively. These concentrations (including the tri
      chlorinated naphthalenes) greatly exceeded concentrations previously measured in
      the Canadian Arctic, but did fall within the upper range of concentrations
      observed over the eastern Arctic Ocean and regional seas. Local sources appear to
      be affecting concentrations observed at both sites, with the presence of several
      hexa-chlorinated naphthalenes at Tromso probably attributed to local/regional
      sources. Use of air mass back trajectories at Tromso revealed that background air
      concentrations in the Norwegian Arctic are likely to range between <9 and 20 pg
      sigmaPCN m(-3) and that contemporary concentrations derived close to potential
      sources (i.e. arctic towns) may equal or exceed those of PCBs. The mean
      concentration in surface snow was 350 and 240 pg sigmaPCN L(-1) (meltwater) (or
      0.014 and 0.01 pg g(-1) (snow)) at Ny-Alesund and Tromso, respectively. The wide
      variation in concentrations observed between fresh snowfalls could be explained
      by different snow densities (as a surrogate of snow surface area), rather than
      attributed to varying air concentrations. A statistically significant inverse
      relationship was found between snow density and concentrations of tri- to penta
      chlorinated homologues and compliments similar findings for the polychlorinated
      biphenyls (PCBs). This suggests that the vapour-sorbed quantity changes rapidly
      with snow ageing/compaction; with implications for the fate of these chemicals in
      the Arctic.

PMID- 15866273
TI  - Gas-particle partitioning of polychlorinated naphthalenes and non- and mono-ortho
      substituted polychlorinated biphenyls in arctic air.
AB  - Gas-particle partitioning relationships were developed for partitioning of
      polychlorinated naphthalenes (PCNs) and non- and mono-ortho PCBs in arctic air by
      regressing observed gas-particle partition coefficients, K(P), at Alert and Dunai
      in the high Arctic with temperature-adjusted experimental vapor pressures (p(L)
      degrees ) and octanol-air partition coefficients (K(OA)). Slopes were near -0.5
      and 0.5 for log p(L) degrees and log K(OA), respectively, at both sites,
      indicating that aerosol characteristics and partitioning processes were similar
      at the two sites. The K(OA) absorption model provided an adequate estimate of the
      percentage of PCNs and non-/mono-ortho PCBs associated with particulate matter,
      based on fraction of organic matter (f(OM)) ranging from 0.074 to 0.12, compared
      to the Junge-Pankow adsorption model, which slightly over-estimated the
      distribution on particles. There were no indications that partitioning to soot
      carbon influences the observed gas-particle distribution for PCNs and non-/mono
      ortho PCBs in arctic air as has been observed for PAHs in recent studies at
      temperate locations.

PMID- 15866274
TI  - Trends of heavy metal components in the Arctic aerosols and their relationship to
      the emissions in the Northern Hemisphere.
AB  - Twenty-one years of observations (1980-2000) of weekly mean concentrations of
      major anthropogenic and natural metals in the aerosol of the lower Arctic
      troposphere at Alert have been analyzed by time series analysis for seasonal and
      long-term trends and by positive matrix factorization for major aerosol
      components with which metals are associated. Metals at Alert exhibit distinct
      seasonal variations depending on the source and origin of the metals.
      Anthropogenic metals such as Pb, Zn and Cu and the sea-salt components Na and Mg
      exhibit maxima in winter and minima in summer. Similar variations were observed
      for non-soil fractions of V and Mn. Weak seasonal variations were found for soil
      related metals such as Al, Ba, Ca and Fe. If any trend is evident in
      anthropogenic metals, it is a slight decrease from 1980 to mid-1990s but
      generally the variation is not monotonic. It is found through the winter
      observations of Pb, Zn, Ni and Cu concentrations that the decline trends have
      been leveled off and started to increase again around 1995. No long-term trends
      were detected in Na, Mg and Ca concentrations but a slight decrease is observed
      for soil components Al, Fe and Ti after 1995. Analysis showed that these trends
      are mostly associated with the anthropogenic emission variations surrounding the
      Arctic regions.

PMID- 15866275
TI  - Mercury in the Arctic atmosphere: an analysis of eight years of measurements of
      GEM at Alert (Canada) and a comparison with observations at Amderma (Russia) and
      Kuujjuarapik (Canada).
AB  - Eight years of gaseous elemental mercury (GEM) concentration measurements from
      Alert, Nunavut, Canada (between 1995 and 2002) is presented. The annual time
      series shows a distinct repeating seasonal pattern with an overall annual median
      concentration for this time period of 1.58 (S.D.=0.04 ng m(-3)). Strong seasonal
      variation was observed throughout the years with springtime displaying strong
      variability in the GEM and overall lower median concentrations due to the so
      called mercury depletion events (MDEs). Summer concentrations are higher than the
      annual average and show a decrease in variability. Fall and winter concentrations
      are distributed around the annual median concentrations and show little
      variability. The relationship between the springtime depression and the summer
      increase shows a change in the behaviour of mercury between 1995 and 2002.
      Preliminary results suggest that during this period an increasing amount of the
      mercury lost from the atmosphere in the spring is not returned to atmosphere in
      summer. A comparison of GEM concentration data from three sites--Alert (Canada),
      Amderma (Russia) and Kuujjuarapik (Canada)--demonstrated similar monthly
      distribution of GEM between Alert and Amderma, with the latter not showing as
      high summer concentrations. Monthly distribution of GEM at Kuujjuarapik varied
      considerably from the other two sites. MDEs were found to occur at each site in
      the spring yet displayed different characteristics. MDEs appear to start at Alert
      shortly after polar sunrise but in Amderma their initiation is delayed
      approximately 2 months following polar sunrise. MDEs occur in Kuujjuarapik in the
      springtime despite an incomplete development of the polar day-night cycle. In
      spring, as soon as air temperature attained temperatures consistently above 0
      degrees C, MDEs ended immediately at all three sites. Continued studies into MDEs
      are warranted, but clearly an important component of future studies must focus on
      the origins of the variation of GEM behaviour at different sites.

PMID- 15866276
TI  - Hydrochemistry and mercury cycling in a High Arctic watershed.
AB  - Mass budgets for total mercury, major ions and nutrients were calculated for
      Amituk Lake, located on Cornwallis Island, Nunavut, Canada. Total mercury in two
      distinct snowpacks averaged 1.25 and 4.21 ng L(-1); the discharge-weighted
      concentration of influent streams averaged 0.76 ng L(-1). The recent and pre
      industrial Hg(T) fluxes in atmospheric deposition to the catchment were estimated
      to be 0.57 and 0.23 microg m(-2) but through retention within the catchment
      and/or re-volatilization from the melting snowpack, these decreased by 69% in the
      lake inflow. The spring freshet was the prime conduit for transporting Hg(T) into
      Amituk Lake. Because of limited mixing of surface runoff with the lake water
      column during snowmelt, 59% of the Hg(T) input was directly discharged through
      the outflow, 16% entered the lake water column where concentrations increased
      from 0.23 to 0.33 ng L(-1) from June to August and 25% was deposited to the
      bottom sediments producing a sediment Hg(T) flux of 3.1 microg m(-2).

PMID- 15866277
TI  - Modern and historical fluxes of halogenated organic contaminants to a lake in the
      Canadian arctic, as determined from annually laminated sediment cores.
AB  - Two annually laminated cores collected from Lake DV09 on Devon Island in May 1999
      were dated using 210Pb and 137Cs, and analyzed for a variety of halogenated
      organic contaminants (HOCs), including polychlorinated biphenyls (PCBs),
      organochlorine pesticides, short-chain polychlorinated n-alkanes (sPCAs),
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), and polybrominated
      diphenyl ethers (PBDEs). Dry weight HOC concentrations in Lake DV09 sediments
      were generally similar to other remote Arctic lakes. Maximum HOC fluxes often
      agreed well with production maxima, although many compound groups exhibited
      maxima at or near the sediment surface, much later than peak production. The
      lower than expected HOC concentrations in older sediment slices may be due to
      anaerobic degradation and possibly to dilution resulting from a temporary
      increase in sedimentation rate observed between the mid-1960s and 1970s. Indeed,
      temporal trends were more readily apparent for those compound classes when
      anaerobic metabolites were also analyzed, such as for DDT and toxaphene. However,
      it is postulated here for the first time that the maximum or increasing HOC
      surface fluxes observed for many of the major compound classes in DV09 sediments
      may be influenced by climate variation and the resulting increase in algal
      primary productivity which could drive an increasing rate of HOC scavenging from
      the water column. Both the fraction (F(TC)) and enantiomer fraction (EF) of trans
      chlordane (TC) decreased significantly between 1957 and 1997, suggesting that
      recent inputs to the lake are from weathered chlordane sources. PCDD/Fs showed a
      change in sources from pentachlorophenol (PeCP) in the 1950s and 1960s to
      combustion sources into the 1990s. Improvements in combustion technology may be
      responsible for the reducing the proportion of TCDF relative to OCDD in the most
      recent slice.

PMID- 15866278
TI  - Fate of organochlorine contaminants in arctic and subarctic lakes estimated by
      mass balance modelling.
AB  - Elevated concentrations of some persistent organic pollutants (POPs) in fish from
      arctic and subarctic lakes have been hypothesized to be due to processes within
      food webs and fish physiology. We investigated limnological processes and
      contaminant chemistry as explanations of these elevated concentrations by
      developing and applying fugacity-based mass balance models to a relatively small
      lake in the high arctic and a series of larger lakes in the southern Yukon River
      basin. The results indicate that high arctic lakes are transient and inefficient
      sinks for POPs. The mobility of POPs in high arctic lakes is conferred by their
      hydrologic regime (i.e. partial through flow of melt water loadings) and minimal
      scavenging and retention in sediments due to extremely low organic carbon in
      settling and sediment particles. Contaminant dynamics in lakes of the south Yukon
      River basin are governed by hydrology (i.e., water residence time), because,
      similarly to high arctic lakes, most of the contaminant inventory resides in the
      water column due to inefficient scavenging by settling particles. For the less
      persistent compounds, long water residence time shifts the major loss process
      from export to degradation. Model results also suggest relatively short
      degradative half-lives of the hexachlorocyclohexanes (sum of HCHs) and
      endosulfan, particularly in high arctic Amituk Lake.

PMID- 15866279
TI  - Observations of the PCB distribution within and in-between ice, snow, ice-rafted
      debris, ice-interstitial water, and seawater in the Barents Sea marginal ice zone
      and the North Pole area.
AB  - To evaluate the two hypotheses of locally elevated exposure of persistent organic
      pollutants (POPs) in ice-associated microenvironments and ice as a key carrier
      for long-range transport of POPs to the Arctic marginal ice zone (MIZ), dissolved
      and particulate polychlorinated biphenyls (PCBs) were analyzed in ice, snow, ice
      interstitial water (IIW), seawater in the melt layer underlying the ice, and in
      ice-rafted sediment (IRS) from the Barents Sea MIZ to the high Arctic in the
      summer of 2001. Ultra-clean sampling equipment and protocols were specially
      developed for this expedition, including construction of a permanent clean room
      facility and a stainless steel seawater intake system on the I/B ODEN as well as
      two mobile 370 l ice-melting systems. Similar concentrations were found in
      several ice-associated compartments. For instance, the concentration of one of
      the most abundant congeners, PCB 52, was typically on the order of 0.1-0.3 pg l(
      1) in the dissolved (melted) phase of the ice, snow, IIW, and underlying seawater
      while its particulate organic-carbon (POC) normalized concentrations were around
      1-3 ng gPOC(-1) in the ice, snow, IIW, and IRS. The solid-water distribution of
      PCBs in ice was well correlated with and predictable from K(ow) (ice log K(oc)
      log K(ow) regressions: p<0.05, r2=0.78-0.98, n=9), indicating near-equilibrium
      partitioning of PCBs within each local ice system. These results do generally not
      evidence the existence of physical microenvironments with locally elevated POP
      exposures. However, there were some indications that the ice-associated system
      had harbored local environments with higher exposure levels earlier/before the
      melting/vegetative season, as a few samples had PCB concentrations elevated by
      factors of 5-10 relative to the typical values, and the elevated levels were
      predominantly found at the station where melting had putatively progressed the
      least. The very low PCB concentrations and absence of any significant
      concentration gradients, both in-between different matrices and over the Eurasian
      Arctic basin scale, suggest that ice is not an important long-range transport
      purveyor of POPs to the Arctic MIZ ecosystem.

PMID- 15866280
TI  - Comparing measured and predicted PCB concentrations in Arctic seawater and marine
      biota.
AB  - When a mechanistic food web model was parameterized for the Arctic marine
      ecosystem, it predicted PCB concentrations in zooplankton and fish that were two
      orders of magnitude lower than measured. PCB concentrations measured in
      zooplankton and fish were within the laboratory's accredited quality assured
      criteria, and were comparable to other Arctic regions. Although on a different
      scale, the predicted and measured PCB concentrations were highly correlated. As
      sensitivity analyses indicated water concentrations as the most sensitive
      parameter for the model output, dissolved water concentrations were predicted
      using measured zooplankton and air PCB concentrations, and empirical and
      mechanistic models. The food web model and the empirical relationship between
      bioaccumulation factor and octanol-water partitioning coefficient predicted mean
      dissolved water concentrations of 28 and 29 pg/L sum of PCB6 (PCB-28, -52, -105, 
      118, -138, -153), respectively. Mean dissolved water concentration predicted from
      measured air concentrations in 1996 was 7.6 pg/L sum of PCB5 (PCB-28 was not
      analysed). Mean dissolved water concentration measured in Barents Sea water
      sampled simultaneously as the biota in 1999 was 0.3 pg/L sum of PCB6. The
      dissolved water concentrations predicted from zooplankton PCB concentrations were
      comparable to water concentrations measured in 1996, whereas the dissolved water
      concentrations measured in 1999 were comparable to measurements from 2001. If the
      present high empirically derived bioaccumulation factors (log BAF 7.3-9.0) were
      realistic, this suggests that bioaccumulation in Arctic zooplankton is more
      efficient that previously assumed. The present study illustrates and discusses
      some of the difficulties encountered when different approaches to study
      environmental distribution of contaminants are compared.

PMID- 15866281
TI  - Presence and distribution of ghrelin-immunopositive cells in the chicken
      gastrointestinal tract.
AB  - The presence and distribution patterns of ghrelin, a gastric acylated peptide,
      were studied in the entire gastrointestinal tract of the chicken (Gallus
      domesticus) using the peroxidase-antiperoxidase immunohistochemical method,
      western blot analysis and a specific antibody against the C-terminal region of
      rat ghrelin. Ghrelin-immunopositive cells were observed in the mucosal layer of
      all segments examined. The largest numbers of ghrelin-positive cells were located
      at the base of lobuli of the proventriculus gland, along villi of the intestines
      and in crypts of the duodenum. Lower numbers of ghrelin-immunostained cells were
      located in crypts of jejunum and ileum and only few ghrelin-immunostained cells
      were detected at the base of crypts of the large intestine. Closed and open types
      of cells were observed in all segments. Western blot analysis confirmed the
      presence of ghrelin-like protein in the entire chicken gastrointestinal tract.
      The anatomical distribution patterns and the morphological characteristics of
      chicken ghrelin-positive cells suggest that they are endocrine cells.
      Furthermore, it is concluded that ghrelin shows a high degree of preservation
      during evolution from non-mammalian vertebrates to mammals.

PMID- 15866282
TI  - Possible autocrine regulation of chromaffin cell activity in adrenal glands of
      the frog by endothelin-1-induced serotonin release.
AB  - The aim of the present study was the demonstration of mechanisms of regulation of
      activity of chromaffin cells in the adrenal gland of Rana ridibunda (Anura
      Amphibia). Previous studies have shown that endothelin-1 is an important factor
      for the maintenance of adrenal gland function. On the basis of these findings,
      frogs were injected with [Ala(1,3,11,15)]-endothelin-1 (0.025 mg/0.2 ml), which
      is a selective agonist of the endothelin B receptor, whereas control animals were
      injected with Ringer solution (0.2 ml). The adrenal glands were removed at 5, 20,
      and 60 min after injection and fixed, embedded in paraffin wax and stained by
      histological and immunohistochemical means, applied on adjacent 4-microm-thick
      sections. Sections were stained with hematoxylin and eosin for overall tissue
      analysis and, in parallel, serotonin was localized using the streptavidin-biotin
      complex technique while dopamine beta-hydroxylase and serotonin 2A receptors were
      shown by the peroxidase-antiperoxidase (PAP)-3,3'-diaminobenzidine tetrachloride
      (DAB) method. After injection of [Ala(1,3,11,15)]-endothelin-1, chromaffin cells
      secreted serotonin and synthesized dopamine beta-hydroxylase. In conclusion,
      these findings suggest that [Ala(1,3,11,15)]-endothelin-1 stimulates chromaffin
      cell activity in frog adrenal glands. Moreover, the presence of serotonin 2A
      receptors in chromaffin cells indicates that these cells are also targets for
      serotonin and that there is an autocrine signaling pathway in chromaffin cells.
      This is the first report providing data on the effects of endothelin-1 on
      chromaffin cells in frog adrenal glands.

PMID- 15866283
TI  - Peritrophic membrane protein in the larval stingless bee Melipona quadrifasciata
      anthidioides: immunolocalization of secretory sites.
AB  - The origin of the peritrophic membrane (PM) in bees is still a matter of debate.
      It is either of type I (synthesized by the entire midgut epithelium) or of type
      II (released from the anterior midgut end). The present study identified
      secretory sites of peritrophin-55 kDa, a PM protein in larvae of Melipona
      quadrifasciata anthidioides. Peritrophin-55 was isolated from PMs and was used
      for the production of a polyclonal antibody. Our study demonstrates the presence
      of peritrophin-55 in vesicles and on microvilli of digestive cells and in the PM.
      It suggests that the PM is of type-I, being specific for the larval phase of this
      stingless bee.

PMID- 15866284
TI  - Glucose-6-phosphate dehydrogenase activity in monolayer cultures of thyroid
      epithelial cells: TSH and inhibition of nitrogen oxide synthase affect the enzyme
      activity and the oxygen sensitivity of the histochemical assay.
AB  - The objective was to investigate glucose-6-phosphate dehydrogenase (G6PD)
      activity in monolayer cultures of thyroid epithelial cells and to examine whether
      inhibition of nitric oxide synthase affects activity of G6PD or oxygen
      sensitivity of the assay. Primary cultures without TSH addition prior to
      experiments demonstrated a TSH-dependent increase in G6PD activity. G6PD activity
      was higher in F12 medium than in a serum-free physiological medium. Secondary
      cultures grown in F12 medium demonstrated a diminished activity of G6PD and a
      lack of response to TSH. In the serum-free physiological medium, G6PD activity
      was comparable to that found in primary cultures and a response to high
      concentrations of TSH was maintained. In primary cultures grown in F12 medium
      devoid of TSH, G6PD activity decreased dose-dependently when nitric oxide
      synthase activity was inhibited. The oxygen sensitivity of the assay was
      comparable to that reported previously in malignant cells and correlated with the
      activity of G6PD in primary cultures. We suggest that thyroid epithelial cells
      may be an appropriate system to investigate oxygen sensitivity of the G6PD assay
      as the cells demonstrate a reduced oxygen sensitivity which can be influenced by
      culture conditions.

PMID- 15866286
TI  - Nuclear iron deposits in hepatocytes of iron-loaded HFE-knock-out mice: a
      morphometric and immunocytochemical analysis.
AB  - Nuclear deposits of stainable iron in hepatocytes are a sign of liver iron
      overload in mice. Animals with no, partial or total knock-out of the HFE alleles,
      the deletion of which is responsible for hereditary haemochromatosis, were given
      different forms of dietary iron to measure nuclear iron deposits which were then
      related to cytoplasmic iron load. Wild type and heterozygous HFE-knock-out mice
      kept for 52 weeks on a standard diet showed no such deposits. These were,
      however, demonstrated in low numbers and with small diameters in homozygous HFE
      knock-out mice kept on this diet. Nuclear iron deposits were most abundant in all
      type of mice fed carbonyl iron (2.5% w/w) for 52 weeks almost irrespective of
      their genetic background. The diameter of these deposits increased with the
      genetically conditioned extent of hepatocellular iron overload. Mice that were
      fed a diet containing TMH-ferrocene for 4 weeks showed amounts of hepatic iron
      that were comparable to those in the carbonyl iron-fed group but nuclear deposits
      were small and present in only 0.3% of the hepatocytes. While surrounding
      karyoplasm was immunostained for H- and L-ferritin, the nuclear iron deposits
      were not. As the nuclear iron deposits corresponded electron microscopically to
      aggregated ferritin molecules, they represent a non-immunoreactive form of
      presumably denatured ferritin.

PMID- 15866285
TI  - Localization of sulfated sialic acids in the dentinal tubules during tooth
      formation in mice.
AB  - Lectin-like properties of the major enamel protein amelogenin suggest that it
      binds to glycoconjugates in dentinal tubules released at the dentin-enamel
      junction (DEJ) during enamel formation. Therefore, a detailed mapping of
      glycosylation in dentinal tubules during tooth formation was undertaken using
      histochemistry and lectin-binding assays. The tubular content exhibited sialidase
      susceptible gamma-metachromasia with Toluidine Blue (pH 2.5) and staining with
      Alcian Blue (pH 1.0). The presence of sulfate groups was confirmed by benzidine
      reactions (Bracco-Curti's and tetrazonium assays). Alpha2,3-, alpha2,6- and
      alpha2,8-sialidases entirely abolished staining with the benzidine reactions. The
      presence of sialic acids in dentinal tubules was confirmed with the Bial's
      reaction and sialidase-susceptible binding of Limax flavus lectin suggesting that
      sialic acids are the major sulfated sugars in the glycoconjguates. Immunostaining
      with the monoclonal antibody 5-D-4 before and after treatment with chondroitin-4-
      and chondroitin-6-sulfatase confirmed the presence of keratan sulfate (KS), a
      sialylated proteoglycan, in dentinal tubules. We suggest that sulfated sialic
      acids are part of the KSs. The sulfated glycoconjugates are also found in dentin
      and the DEJ but not in predentin suggesting that amelogenin binds to the
      sialoconjugate during enamel formation.

PMID- 15866287
TI  - Effects of electroacupuncture with different frequencies on spinal ionotropic
      glutamate receptor expression in complete Freund's adjuvant-injected rat.
AB  - We investigated expressional changes of spinal glutamate receptors by
      electroacupuncture (EA) in an inflammatory animal model. Inflammation was induced
      by an intraplantar injection of complete Freund's adjuvant (CFA) into the hindpaw
      of male Sprague-Dawley rats. Bilateral EA stimulation at 2, 15 and 120 Hz was
      applied at those acupoints corresponding to Zusanli and Sanyinjiao in man using
      needles with 3-day intervals for 30 days. Paw edema and mechanical thresholds
      were measured by a water displacement plethysmometer and Analgesy-Meter,
      respectively. Edema and mechanical sensitivity of the hindpaw induced by CFA
      injection were strongly inhibited by EA stimulation. At 30 days after CFA
      injection, effects of EA on ionotropic glutamate receptor (NR-1, NR-2A, GluR-1
      and GluR-2/3) expression in association with c-fos and calcitonin gene-related
      peptide (CGRP) expression were observed in the dorsal horn of the spinal cord
      using immunohistochemistry. The number of c-fos-like immunostained cells was
      decreased significantly in the superficial laminae of the dorsal horn by 2Hz EA,
      but CGRP expression also showed a marked decrease in the same region using the
      other types of EA stimulation. N-methyl-D-aspartate receptor (NR-1 and NR-2A)
      expression was attenuated in all regions of the dorsal horn by all types of EA.
      Of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (GluR-1
      and -2/3), only GluR-1 expression was prevented by EA treatment in the
      superficial laminae and the neck of the dorsal horn. It is concluded that EA
      treatment can attenuate inflammatory edema and mechanical thresholds in CFA
      injected rats through modulating expression of ionotropic glutamate receptors,
      and especially N-methyl-D-aspartate receptors, in the dorsal horn of the spinal
      cord.

PMID- 15866288
TI  - Effects of inhibition of urokinase-type plasminogen activator (u-PA) by amiloride
      in the cornea and tear fluid of eyes irradiated with UVB.
AB  - The purpose of the present study was to test our hypothesis that amiloride, a
      specific u-PA inhibitor, effectively decreases u-PA activity in cornea as well as
      in tear fluid and favourably affects corneal healing. Therefore, comparative
      histochemical and biochemical studies of u-PA and the effects of amiloride were
      performed on rabbit corneas and tear fluid using the sensitive fluorogenic
      substrate Z-Gly-Gly-Arg-7-amino-4-trifluoromethylcoumarin. Rabbit eyes were
      repeatedly irradiated with UVB for 9 days and during the irradiation topically
      treated with amiloride (1 mg/ml saline) or placebo (saline) (dropwise, 5 times
      daily). Results show that in placebo-treated eyes, UVB evoked the appearance of u
      PA activity in cornea and tear fluid in early stages of irradiation, and u-PA
      levels increased during irradiation. Corneal epithelium was gradually lost and
      remnants of the epithelium as well as keratocytes in the upper part of corneal
      stroma showed high u-PA activity. Finally, corneas lost their epithelium
      completely. In corneal stroma, numerous u-PA-containing inflammatory cells were
      present. Corneas were vascularized. When amiloride was dropped on the eye surface
      on the first day of irradiation and subsequently daily until the end of the
      experiment, u-PA activity in both cornea and tear fluid was strongly inhibited.
      Corneas were covered with a continuous epithelium until the end of the
      experiment. The number of inflammatory cells was significantly decreased. Corneal
      vascularization was reduced by 50%. In conclusion, early application of amiloride
      inhibited u-PA activity in UVB-irradiated corneas as well as in tear fluid and
      diminished the development of corneal pathology.

PMID- 15866289
TI  - Hormones and endometrial cancer--new data from the Million Women Study.

PMID- 15866290
TI  - Still looking for answers in COPD.

PMID- 15866291
TI  - Extending the benefits of deworming for development.

PMID- 15866292
TI  - Non-HLA humoral immunity and chronic kidney-graft loss.

PMID- 15866293
TI  - Shanghai plans responses to AIDS.

PMID- 15866294
TI  - Dissolving the dilemma over forced treatment.

PMID- 15866295
TI  - World Diabetes Day: footing the bill.

PMID- 15866296
TI  - thelancet.com-new horizons.

PMID- 15866298
TI  - Increased risk of cardiovascular events with coxibs and NSAIDs.

PMID- 15866299
TI  - Increased risk of cardiovascular events with coxibs and NSAIDs.

PMID- 15866300
TI  - Increased risk of cardiovascular events with coxibs and NSAIDs.

PMID- 15866301
TI  - Increased risk of cardiovascular events with coxibs and NSAIDs.

PMID- 15866302
TI  - Screening for chlamydia.

PMID- 15866303
TI  - Screening for chlamydia.

PMID- 15866304
TI  - HCV-indeterminate blood donors or occult HCV infection?

PMID- 15866305
TI  - Appropriate technology in tuberculosis diagnostics.

PMID- 15866307
TI  - Strangulation by intravenous tubes.

PMID- 15866308
TI  - Endometrial cancer and hormone-replacement therapy in the Million Women Study.
AB  - BACKGROUND: Postmenopausal women who use hormone-replacement therapy (HRT)
      containing oestrogen alone are at increased risk of endometrial cancer. To
      minimise this risk, many HRT users who have not had a hysterectomy use combined
      oestrogen-progestagen preparations or tibolone. Limited information is available
      on the incidence of endometrial cancer in users of these therapies. METHODS:
      716,738 postmenopausal women in the UK without previous cancer or previous
      hysterectomy were recruited into the Million Women Study in 1996-2001, provided
      information about their use of HRT and other personal details, and were followed
      up for an average of 3.4 years, during which time 1320 incident endometrial
      cancers were diagnosed. FINDINGS: 320,953 women (45%) reported at recruitment
      that they had used HRT, among whom 69,577 (22%) last used continuous combined
      therapy (progestagen added daily to oestrogen), 145,486 (45%) last used cyclic
      combined therapy (progestagen added to oestrogen, usually for 10-14 days per
      month), 28,028 (9%) last used tibolone, and 14,204 (4%) last used oestrogen-only
      HRT. These HRT types had sharply contrasting effects on the overall risk of
      endometrial cancer (p<0.0001 for heterogeneity). Compared with never users of
      HRT, risk was: reduced with last use of continuous combined preparations
      (relative risk 0.71 [95% CI 0.56-0.90]; p=0.005); increased with last use of
      tibolone (1.79 [1.43-2.25]; p<0.0001) and oestrogen only (1.45 [1.02-2.06];
      p=0.04); and not significantly altered with last use of cyclic combined
      preparations (1.05 [0.91-1.22]; p=0.5). A woman's body-mass index significantly
      affected these associations, such that the adverse effects of tibolone and
      oestrogen-only HRT were greatest in non-obese women, and the beneficial effects
      of combined HRT were greatest in obese women. INTERPRETATION: Oestrogens and
      tibolone increase the risk of endometrial cancer. Progestagens counteract the
      adverse effect of oestrogens on the endometrium, the effect being greater the
      more days every month that they are added to oestrogen and the more obese that
      women are. However, combined oestrogen-progestagen HRT causes a greater increase
      in breast cancer than the other therapies do. Thus, when endometrial and breast
      cancers are added together, there is a greater increase in total cancer incidence
      with use of combined HRT, both continuous and cyclic, than with use of the other
      therapies.

PMID- 15866309
TI  - Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease
      (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo
      controlled trial.
AB  - BACKGROUND: Increased oxidative stress is important in the pathogenesis of
      chronic obstructive pulmonary disease (COPD). We postulated that treatment with
      the antioxidant N-acetylcysteine would reduce the rate of lung-function decline,
      reduce yearly exacerbation rate, and improve outcomes. METHODS: In a randomised
      placebo-controlled study in 50 centres, 523 patients with COPD were randomly
      assigned to 600 mg daily N-acetylcysteine or placebo. Patients were followed for
      3 years. Primary outcomes were yearly reduction in forced expiratory volume in 1
      s (FEV1) and the number of exacerbations per year. Analysis was by intention to
      treat. FINDINGS: The yearly rate of decline in FEV1 did not differ between
      patients assigned N-acetylcysteine and those assigned placebo (54 mL [SE 6] vs 47
      mL [6]; difference in slope between groups 8 mL [9]; 95% CI -25 to 10). The
      number of exacerbations per year did not differ between groups (1.25 [SD 1.35] vs
      1.29 [SD 1.46]; hazard ratio 0.99 [95% CI 0.89-1.10, p=0.85]). Subgroup analysis
      suggested that the exacerbation rate might be reduced with N acetylcysteine in
      patients not treated with inhaled corticosteroids and secondary analysis was
      suggestive of an effect on hyperinflation. INTERPRETATION: N-acetylcysteine is
      ineffective at prevention of deterioration in lung function and prevention of
      exacerbations in patients with COPD.

PMID- 15866310
TI  - Reassessment of the cost of chronic helmintic infection: a meta-analysis of
      disability-related outcomes in endemic schistosomiasis.
AB  - BACKGROUND: Schistosomiasis is one of the world's most prevalent infections, yet
      its effect on the global burden of disease is controversial. Published disability
      adjusted life-year (DALY) estimates suggest that the average effect of
      schistosome infection is quite small, although this is disputed. To develop an
      evidenced-based reassessment of schistosomiasis-related disability, we did a
      systematic review of data on disability-associated outcomes for all forms of
      schistosomiasis. METHODS: We did structured searches using EMBASE, PUBMED, and
      Cochrane electronic databases. Published bibliographies were manually searched,
      and unpublished studies were obtained by contacting research groups. Reports were
      reviewed and abstracted independently by two trained readers. All randomised and
      observational studies of schistosomiasis morbidity were eligible for inclusion.
      We calculated pooled estimates of reported disability-related effects using
      weighted odds ratios for categorical outcomes and standardised mean differences
      for continuous data. FINDINGS: 482 published or unpublished reports (March, 1921,
      to July, 2002) were screened. Of 135 selected for inclusion, 51 provided data for
      performance-related symptoms, whereas 109 reported observed measures of
      disability-linked morbidities. Schistosomiasis was significantly associated with
      anaemia, chronic pain, diarrhoea, exercise intolerance, and undernutrition.
      INTERPRETATION: By contrast with WHO estimates of 0.5% disability weight assigned
      to schistosomiasis, 2-15% disability seems evident in different functional
      domains of a person with schistosomiasis. This raised estimate, if confirmed in
      formal patient-preference studies, indicates a need to reassess our priorities
      for treating this silent pandemic of schistosomiasis.

PMID- 15866311
TI  - Non-HLA transplantation immunity revealed by lymphocytotoxic antibodies.
AB  - BACKGROUND: The presence of panel-reactive antibodies (PRA) against HLA antigens
      before transplantation is associated with early rejection of kidney grafts from
      cadaver donors. Transplants from HLA-identical sibling donors do not provide a
      target for antibodies to HLA antigens and should therefore not be affected by
      PRA. METHODS: Data from the Collaborative Transplant Study were used to examine
      the influence of PRA on graft survival. Uncensored graft survival and death
      censored graft survival were calculated, and the data were analysed by
      multivariate Cox's regression methods. FINDINGS: Among recipients of HLA
      identical sibling transplants, 3001 patients with no PRA had significantly higher
      10-year graft survival (72.4% [SE 1.1]) than 803 patients with 1-50% PRA (63.3%
      [2.5]; p=0.0006) or 244 patients with more than 50% PRA (55.5% [4.0]; p<0.0001).
      The effect of PRA became apparent after the first post-transplant year and was,
      therefore, strikingly different from the early steep decline in graft survival
      during the first year associated with PRA in recipients of cadaver kidneys. We
      could not discern whether graft loss was a direct effect of non-HLA humoral
      sensitisation or whether PRA served as an indicator of heightened immunity
      against non-HLA transplantation antigens. INTERPRETATION: PRA reactivity is
      strongly associated with long-term graft loss in kidney transplants from HLA
      identical sibling donors. RELEVANCE TO PRACTICE: Our findings suggest that non
      HLA immunity has a much stronger role in clinical transplantation than previously
      thought. In contrast to immunity against HLA mediated by antibodies present
      before transplantation, which leads to early acute graft rejection, non-HLA
      immunity is associated with chronic graft loss. The possibility of identifying
      recipients at increased risk of late graft loss before transplantation could be
      used to devise specific immunosuppressive strategies for these patients.

PMID- 15866312
TI  - Abdominal aortic aneurysm.
AB  - Abdominal aortic aneurysms cause 1.3% of all deaths among men aged 65-85 years in
      developed countries. These aneurysms are typically asymptomatic until the
      catastrophic event of rupture. Repair of large or symptomatic aneurysms by open
      surgery or endovascular repair is recommended, whereas repair of small abdominal
      aortic aneurysms does not provide a significant benefit. Abdominal aortic
      aneurysm is linked to the degradation of the elastic media of the atheromatous
      aorta. An inflammatory cell infiltrate, neovascularisation, and production and
      activation of various proteases and cytokines contribute to the development of
      this disorder, although the underlying mechanisms are unknown. In this Seminar,
      we aim to provide an updated review of the pathophysiology, current and new
      diagnostic procedures, assessment, and treatment of abdominal aortic aneurysm to
      provide family practitioners with a working knowledge of this disorder.

PMID- 15866313
TI  - Aortic aneurysm: the physician as patient.

PMID- 15866314
TI  - Multiplicity in randomised trials I: endpoints and treatments.
AB  - Multiplicity problems emerge from investigators looking at many additional
      endpoints and treatment group comparisons. Thousands of potential comparisons can
      emanate from one trial. Investigators might only report the significant
      comparisons, an unscientific practice if unwitting, and fraudulent if
      intentional. Researchers must report all the endpoints analysed and treatments
      compared. Some statisticians propose statistical adjustments to account for
      multiplicity. Simply defined, they test for no effects in all the primary
      endpoints undertaken versus an effect in one or more of those endpoints. In
      general, statistical adjustments for multiplicity provide crude answers to an
      irrelevant question. However, investigators should use adjustments when the
      clinical decision-making argument rests solely on one or more of the primary
      endpoints being significant. In these cases, adjustments somewhat rescue
      scattershot analyses. Readers need to be aware of the potential for under
      reporting of analyses.

PMID- 15866315
TI  - A blood donor with bacteraemia.

PMID- 15866316
TI  - Evidence for novel cannabinoid receptors.
AB  - Cannabinoids, including the bioactive constituents of the marijuana plant, their
      synthetic analogs, and endogenous lipids with cannabinoid-like activity, produce
      their biological effects by interacting with specific receptors. To date, two G
      protein-coupled cannabinoid receptors have been identified by molecular cloning,
      CB1 receptors mainly expressed in the brain and mediating most of the
      neurobehavioral effects of cannabinoids and CB2 receptors expressed by immune and
      hematopoietic tissues. Recent findings indicate that some cannabinoid effects are
      not mediated by either CB1 or CB2 receptors, and in some cases there is
      compelling evidence to implicate additional receptors in these actions. These
      include transient receptor potential vanilloid 1 (TRPV1) receptors and as-yet
      unidentified receptors implicated in the endothelium-dependent vasodilator effect
      of certain cannabinoids and in the presynaptic inhibition of glutamatergic
      neurotransmission in the hippocampus. The case for these additional receptors is
      being reviewed here.

PMID- 15866317
TI  - Modulation of apoptosis by nitric oxide: implications in myocardial ischemia and
      heart failure.
AB  - The purpose of this review is to summarize the regulation of apoptosis by nitric
      oxide (NO) and to discuss the potential role that NO plays in cardiomyocyte
      apoptosis during myocardial ischemia/reperfusion and development of heart
      failure. NO is an important regulator of apoptosis within the mammalian system,
      capable of both inducing and preventing apoptosis, depending upon the level of NO
      production and environmental milieu. This bifunctional capacity is well
      illustrated in the heart. It appears that high levels of NO produced by inducible
      nitric oxide synthase (iNOS) promote apoptosis while basal levels of NO
      production from endothelial nitric oxide synthase (eNOS) protect cardiomyocytes
      from apoptosis. Since permanent loss of cardiomyocytes due to apoptosis
      contributes to the development of heart failure, inhibition of cardiomyocyte
      apoptosis may have therapeutic implications. Given its pro- and anti-apoptotic
      capacity within the heart, NO may serve as a valuable therapeutic target in
      myocardial ischemia and heart failure.

PMID- 15866318
TI  - Cytokines in multiple sclerosis: from bench to bedside.
AB  - Cytokines play an important role in the pathogenesis of inflammatory diseases
      including multiple sclerosis (MS). Experimental models have played a critical
      role in unraveling the roles of individual cytokines in this disease; however,
      these studies occasionally yield conflicting results, highlighting the complex
      role cytokines play in the disease process. Efforts to modulate cytokine function
      in MS have shown that effective treatments alter cytokine expression in the
      central nervous system (CNS) and in activated mononuclear cells, indicating that
      they are important therapeutic targets. In this review, we will summarize the
      current knowledge on the role of cytokine pathways in MS and what we learned from
      investigation of its animal model: experimental autoimmune encephalomyelitis
      (EAE).

PMID- 15866319
TI  - Contribution of natural products to the discovery of the transient receptor
      potential (TRP) channels family and their functions.
AB  - Members of the transient receptor potential (TRP) family of nonselective cation
      channels are involved in several pathological and physiological conditions. The
      search for the molecular targets for naturally occurring substances, especially
      from plants, allowed the characterization of many TRP channels. In fact, attempts
      to understand the hot and painful action of the vanillyl group containing
      compounds capsaicin (from Capsicum sp.) and its ultrapotent analogue
      resiniferatoxin (RTX, from Euphorbia sp.) led to the cloning of the vanilloid
      receptor (TRPV1) 7 years ago. TRPV1 is found in sensory fibers and functions as a
      molecular integrator of several painful stimuli, being especially stimulated
      during inflammation. Since TRPV1 is involved in several pathological conditions,
      selective ligands or modulators of this channel are substances of potential
      interest to treat such diseases. Once again, natural products seem to be also
      interesting sources of compounds that might be prototype TRPV1 ligands. The
      cloning of TRPV1 also enabled the discovery of other members of the TRPV family
      of channels. Similar to TRPV1, these receptors function as molecular detectors of
      physical and chemical stimuli, such as innocuous and noxious heat, as well as
      mechanical force. Recently, novel TRP channels sensitive to low temperatures also
      have been cloned, namely, TRPM8 and TRPA1. Such channels are also activated by
      naturally occurring substances but knowledge of their involvement in health and
      disease is in its infancy. In the present review, we focused on the contribution
      of natural products to the discovery of TRP channels and to the development of
      novel drugs to treat pathological conditions in which these channels are
      involved.

PMID- 15866320
TI  - Interaction between nitric oxide and the cholinergic and sympathetic nervous
      system in cardiovascular control in humans.
AB  - Evidence has accumulated indicating that the interaction between NO and the
      autonomic nervous system plays an important role in cardiovascular regulation,
      not only in experimental animals, but also in humans. NO interacts with the
      autonomic nervous system both at the central level and peripherally. In this
      review, we will summarize the current understanding of this interaction in normal
      humans, and discuss pathophysiological consequences that occur, when this
      interaction is altered. We provide evidence for the concept that the primary
      effect of NO in humans is a reduction of basal sympathetic vasoconstrictor tone,
      rather than inhibition of the excitability of this system. Impaired NO synthesis
      in humans therefore promotes sustained vasoconstriction by 2 distinct mechanisms:
      loss of vasodilator tone at vascular smooth muscle cells and by facilitating
      central neural vasoconstrictor outflow. Insulin resistance, essential
      hypertension and end-stage renal failure are examples of diseases, where impaired
      NO buffering of neural outflow may contribute to sustained sympathetic
      activation. In addition to the sympathetic nervous system, NO also interacts with
      the cholinergic nervous system. Cholinergic mechanisms play a major, hitherto
      unrecognised, role in offsetting the arterial hypertension and cardiac
      sympathetic activation caused by inhibition of NO synthesis in normal humans.
      While further studies are needed to determine the exact underlying mechanism(s)
      by which NO and the autonomic nervous system interact in humans, these findings
      provide the conceptual framework for the use of therapeutic interventions that
      deliver NO and/or modulate the bioavailability of endogenously produced NO to
      adjust the autonomic control of the circulation in humans.

PMID- 15866321
TI  - WNK kinases and the control of blood pressure.
AB  - The WNK kinases are a small group of serine/threonine kinases with unique
      catalytic domains that lack the lysine residue used in other kinases to co
      ordinate ATP (hence, With No K [WNK]). Their closest homologues are found within
      the mitogen-activated protein kinase (MAPK) pathway suggesting a role in
      signalling. Two WNK isoforms, WNK1 and WNK4, have been identified as the disease
      genes for a rare monogenic hypertension syndrome (Gordon's syndrome or
      pseudohypoaldosteronism type 2 [PHA2]) implicating them in salt homeostasis by
      the kidney. This is supported by recent data showing widespread expression of
      WNK1 and WNK4 in mammalian transporting epithelia. Within the kidney, WNKs
      probably regulate the surface expression of several proteins involved in ion
      transport, including the sodium-chloride cotransporter (NCCT) and the potassium
      channel renal outer medullary potassium channel (ROMK), based on co-expression
      studies in Xenopus oocytes. WNKs, especially WNK4, have been suggested as
      candidate genes for essential hypertension itself, but evidence for this is
      lacking. Some of the effects of the WNKs are independent of their kinase
      function, suggesting that they are dependent on specific protein-protein
      interactions. It seems likely that the WNKs are part of much larger protein
      scaffolds in cells and have effects in cells beyond ion transport. However,
      because of their effect on expression of the NCCT they are attractive drug
      targets for the development of novel antihypertensive agents. These agents could
      potentially offer the efficacy of a thiazide diuretic, but without the metabolic
      side effects usually seen with this class of antihypertensive therapy.

PMID- 15866322
TI  - Nitric oxide and penile erectile function.
AB  - The discovery of nitric oxide (NO) as an intercellular messenger or
      neurotransmitter opened a new era for identifying the important mechanisms
      underlying physiological and pathophysiological events in autonomically
      innervated organs and tissues; it also provided the way for development of new
      therapeutics based on a novel concept of molecule and cell interaction.
      Endothelium-derived relaxing factor (EDRF) discovered by Furchgott and Zawadzki
      has been proved to be NO, a labile gaseous molecule, that modulates vascular
      tone, platelet aggregation and adhesion, and vascular smooth muscle
      proliferation. Later, NO was determined to act as a non-adrenergic, non
      cholinergic (NANC) neurotransmitter of postganglionic parasympathetic nerve
      fibers, innervating a variety of smooth muscles including the penile corpus
      cavernosum (CC). The nerve is called "nitrergic" or "nitroxidergic". Although CC
      sinusoidal endothelial cells also produce and liberate NO in response to chemical
      and possibly physical stimuli, roles of neurogenic NO in penile erection appear
      to be more attractive and convincing. NO is formed from L-arginine via catalysis
      by NO synthase (NOS) isoforms, neuronal (nNOS), endothelial (eNOS), and inducible
      NOS. NO from nerves and possibly endothelia plays a crucial role in initiating
      and maintaining intracavernous pressure increase, penile vasodilatation, and
      penile erection that are dependent on cyclic GMP synthesized with activation of
      soluble guanylyl cyclase by NO in smooth muscle cells. Erectile dysfunction (ED)
      is caused by a variety of pathogenic factors, particularly impaired formation and
      action of NO. Thus, replenishment of this molecule or intracellular cyclic GMP is
      expected so far to be the most promising therapeutic measures for patients with
      ED. This article includes recent advances in research on physiological roles and
      pathophysiological implications of NO in penile erection and on novel therapy for
      ED in reference to NO.

PMID- 15866324
TI  - Discussion on "Towards a quantitative characterization of functional states of
      the brain: from the non-linear methodology to the global linear description" by
      J. Wackermann.
AB  - Wackermann (1999) [Wackermann, J., 1999. Towards a quantitative characterization
      of functional states of the brain: from the non-linear methodology to the global
      linear description. Int. J. Psychophysiol. 34, 65-80] proposed Sigma-phi-Omega
      system for describing the global brain macro-state, in which Omega complexity was
      used to quantify the degree of synchrony between spatially distributed EEG
      processes. In this paper the effect of signal power on Omega complexity is
      discussed, which was not considered in Wackermann's paper (1999). Then an
      improved method for eliminating the effect of signal power on Omega complexity is
      proposed. Finally a case study on the degree of synchrony between two-channel EEG
      signals over different brain regions during hand motor imagery is given. The
      results show that the improved Omega complexity measure would characterize the
      true degree of synchrony among the EEG signals by eliminating the influence of
      signal power.

PMID- 15866325
TI  - SOA-dependent N400 and P300 semantic priming effects using pseudoword primes and
      a delayed lexical decision.
AB  - In a previous semantic priming study, we found a semantic distance effect on the
      lexical-decision-related P300 when SOA was short (150 ms) only, but no different
      RT and N400 priming effects between short and long (700 ms) SOAs. To investigate
      this further, we separated priming from lexical decision, using a delayed lexical
      decision in the present study. In the short SOA only, primed targets evoked an
      early peaking (approximately 480 ms) P300-like component, probably because the
      subject detected the semantic relationship implicitly. We hypothesize that in
      tasks requiring an immediate lexical decision, this early P300 and the later
      lexical decision P300 (approximately 600 ms) are additive. Secondly, we found
      both a direct and an indirect priming effect for both SOAs for the ERP amplitude
      of the N400 time window. However the N400 component itself was considerably
      larger in the long SOA than in the short SOA. We interpreted this finding as an
      ERP correlate for deeper semantic processing in the long SOA, due to increased
      attention that was provoked by the use of pseudoword primes. In contrast, in the
      short SOA, subjects might have used a shallowed semantic processing. N400, P300,
      and RTs are sensitive to semantic priming-but the modulation patterns are not
      consistent. This raises the question as to which variable reflects an immediate
      physiological correlate of semantic priming, and which variable reflects co
      occurring processes associated with semantic priming.

PMID- 15866326
TI  - Differences in induced gamma and upper alpha oscillations in the human brain
      related to verbal/performance and emotional intelligence.
AB  - Participating in the study were 30 respondents, who could be clustered as high
      average verbal/performance intelligent (HIQ/AIQ), or emotionally intelligent
      (HEIQ/AEIQ). The EEG was recorded while students were performing two tasks: the
      Raven's advanced progressive matrices (RAPM), and identifying emotions in
      pictures (IDEM). Significant differences in event-related
      desynchronization/synchronization (ERD/ERS) related to verbal/performance
      intelligence were only observed while respondents solved the RAPM. The HIQ and
      AIQ groups displayed temporal and spatial differently induced gamma band
      activity. Significant differences in ERD/ERS related to emotional intelligence
      were only observed for the IDEM task. HEIQ individuals displayed more gamma band
      ERS and less upper alpha band ERD than did AEIQ individuals. It can be concluded
      that HIQ and HEIQ individuals employed more adequate strategies for solving the
      problems at hand. The results further suggest that emotional intelligence and
      verbal/performance intelligence represent distinct components of the cognitive
      architecture.

PMID- 15866327
TI  - Brain electrical activity changes in treatment refractory schizophrenics after
      olanzapine treatment.
AB  - The aim of the present study was to identify brain electrical activity changes
      generated by olanzapine (OLZ) in treatment refractory schizophrenics (TRS). 14
      paranoid TRS (31.5+/-8.39 years old) were evaluated before and after 8 weeks of
      OLZ treatment. Psychopathology was evaluated by means of total BPRS and PANSS
      scores. Resting EEG was recorded in the pre (under typical neuroleptics) and post
      (under OLZ) sessions. A good response to OLZ was observed in 57% of TRS. A
      significant reduction in positive and negative symptoms scales of PANSS was
      found. Absolute power of theta1, theta2, alpha1 bands increased after treatment,
      while beta2 power showed a decrease. Intrahemispheric correlation increased
      between different zones of the frontal areas and between frontal and posterior
      areas, while interhemispheric correlation decreased in theta2. EEG changes were
      more evident in those patients who had a better response to OLZ. OLZ showed to be
      effective in TRS, improving psychiatric symptoms and increasing activity
      synchronization between different areas within each hemisphere that may indicate
      a functional reorganization, particularly in good responders.

PMID- 15866328
TI  - Functional clustering in EEG photic and auditory driving in schizophrenia.
AB  - The purpose of this study is to investigate the effects of photic and auditory
      stimuli on brain functions in schizophrenics by investigating the functional
      cluster (FC) of EEGs. We recorded EEGs using 16 electrodes on 10 schizophrenic
      patients and on 10 normal controls during photic and auditory stimuli. We
      estimated FC would characterize the strongly interactive brain regions among many
      brain regions. FC refers to the brain regions that interact much more strongly
      among themselves than with the rest of the brain. Brain regions that belong to
      the same cluster are therefore all functionally involved while, presumably, the
      regions that belong to separate clusters are functionally unrelated. When photic
      and auditory stimuli are applied, the schizophrenic patients have a very similar
      cluster composed of the right temporal and occipital regions for both conditions,
      whereas the normal controls show the normally driven information stream from the
      posterior areas to the prefrontal cortex. Our findings may suggest that in
      schizophrenics the right temporal and occipital regions strongly interact with
      neuronal activities not only in the resting condition but also during the
      stimulation condition. In addition, this strong interaction supports the abnormal
      brain functional connectivity and the dysfunction of the cortical structure
      during photic and auditory stimuli. Our study shows the existence and different
      pattern of FCs for normal controls and schizophrenics. Thus, FC analysis would be
      a potential tool to investigate the simultaneous neuronal activity of human EEGs.

PMID- 15866329
TI  - The influence of anxiety on electrodermal responses to distractors.
AB  - Contrary to classical expectation, anxiety has been repeatedly observed to be
      associated with reduced electrodermal activity. This could be the result of
      successful coping. In line with this interpretation, high-trait anxious
      individuals performing moderately arousing tasks were expected to manifest a
      reduced responding to distractors, since this is an adaptive outcome. High- and
      low-trait anxious participants had to perform a visual search task in a low
      stress context. Unrelated neutral and emotional auditory words served as
      distractors. As a control, neutral and emotional words were also delivered in a
      no task condition. Skin conductance responses (SCRs) were greater during the task
      than during the control phase, but in the high anxious group, this increase in
      SCRs was smaller following emotional distractors than following neutral ones.
      Moreover, SCRs to both types of words habituated, but the results suggested that
      only the low-trait anxious participants presented the classical slowing of SCRs
      habituation when performing the task. All these data are interpreted as an
      illustration of a resource-based electrodermal inhibition in the high-trait
      anxious participants. It sustains the idea that mild to moderate anxiety may
      increase the mastery of situations.

PMID- 15866330
TI  - Non-conscious modulation of cardiac defense by masked phobic pictures.
AB  - The present study investigated the modulation of cardiac defense by presenting
      emotional pictures under both effective and non-effective masking procedures. The
      aim was to test Ohman's model of pre-attentive processing of fear. Participants
      were 48 women volunteers with intense fear of spiders. The stimulus to elicit
      cardiac defense was a white noise of 105 dB, 500 ms duration and instantaneous
      risetime. Subjects had two trials of picture-noise presentation-one with a
      picture of a spider and one with a picture of a flower-, either under an
      effective masking procedure (30 ms duration) or a non-effective masking procedure
      (500 ms duration). Order of presentation was counterbalanced. Dependent variables
      were heart rate and subjective assessment of the noise. Results showed an
      increased cardiac response in the first trial and a less reduced cardiac response
      in the second trial when the noise was preceded by the phobic picture under both
      masking procedures. The response was accompanied by an increase in the subjective
      unpleasantness of the noise. These results provide support to Ohman's theoretical
      model.

PMID- 15866331
TI  - Review of novel particulate antigen delivery systems with special focus on
      treatment of type I allergy.
AB  - For the treatment of infectious diseases, cancer and allergy, the directed
      induction of an appropriate immune response is the ultimate goal. Therefore, with
      the development of pure, often very small proteins, peptides or DNA by molecular
      biology techniques, the research for suitable adjuvants or delivery systems
      became increasingly important. Particle formulations are made of a variety of
      materials, including lipids, proteins or amino acids, polysaccharides,
      polyacrylic substances or organic acids. Microparticles serve as vehicles and
      provide a depot for the entrapped or coupled antigen. The release occurs in a
      pulsatile or continuous manner, a feature, which is well controllable for many
      particulate systems. Particles attract antigen presenting cells to the
      administration site, thereby guaranteeing the efficient presentation of the
      antigen to the immune system. Importantly, particles also protect the entrapped
      substance. This is especially necessary after oral application to avoid gastric
      or tryptic breakdown. In this article, the design and construction of different
      antigen delivery systems and their immune effects, with special focus on the
      suitability for allergy treatment, are discussed.

PMID- 15866332
TI  - Successful treatment of photo-damaged skin of nano-scale atRA particles using a
      novel transdermal delivery.
AB  - We show a novel drug delivery system (DDS) for improved all-trans retinoic acid
      (atRA) therapy for external treatments of photo-damaged skin. We prepared
      inorganic-coated atRA nanoparticles, in turn an egg-like structure in nano-scale
      (Nano-atRA), using boundary-organized reaction droplets. The interfacial
      properties of organic architectures, in atRA micelles, were used to template the
      nucleation of inorganic minerals. As a result, irritation and inflammation
      associated with atRA therapy were substantially reduced due to the complete
      encapsulation of the carboxylic function. Both irritative symptoms and
      physicochemical instability of the atRA micelle were improved. Since Nano-atRA
      which is prepared following to this new DDS system developmentally improved the
      permeability to the stratum corneum, the remarkable pharmacological effects were
      resulted in comparison with atRA as such as follows: (1) thicker epidermis than
      classical atRA treatment and (2) the overexpression of mRNA for heparin-binding
      epidermal growth factor (HB-EGF) as the provocation epidermal hyperplasia.
      Furthermore, we found a surprising boost in production of hyaluronan (HA) among
      the intercellular spaces of the basal and spinous cell layers in epidermis. Nano
      atRA technology for atRA therapy could not only efficiently regulate keratinocyte
      cell proliferation and differentiation, but also markedly produce the additional
      benefit. Severely injured human skin by chronic ultraviolet irradiation will
      completely repair due to the accelerated turnover of skin tissue, which is
      induced by Nano-atRA.

PMID- 15866333
TI  - Biodegradable derivatives of tranexamic acid as transdermal permeation enhancers.
AB  - The purpose of this work was to develop a novel approach to transdermal
      permeation enhancer design, based on utilizing some favorable properties of their
      metabolites. As an example of this concept, a series of carbamic acid salts of
      tranexamic acid (TXA) esters was synthesized, because TXA was previously shown to
      improve skin barrier homeostasis. Enhancement activities of 1% TXA derivatives
      dispersed in both hydrophilic and lipophilic vehicles were evaluated in vitro
      using human skin and theophylline as a model drug. Dispersed in an aqueous donor
      vehicle, the dodecyl ester showed the enhancement ratio (ER) of 4.3+/-0.9, which
      is almost 2 times higher than that of 1-dodecylazepan-2-one (Azone; 2.2+/-0.7).
      From an isopropyl-myristate suspension, the decyl ester was the most effective
      enhancer (4.9+/-1.4), while Azone was inactive. Decomposition of the carbamate in
      a slightly acidic environment was shown by FTIR; hydrolysis of the pertinent
      ester by porcine esterase was monitored by TLC and HPLC. Biodegradable enhancers
      of this type could mediate easier and faster recovery of the skin barrier after
      transdermal delivery through the action of the released TXA.

PMID- 15866334
TI  - Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug
      delivery.
AB  - To overcome the skin's barrier properties that block transdermal delivery of most
      drugs, arrays of microscopic needles have been microfabricated primarily out of
      silicon or metal. This study addresses microneedles made of biocompatible and
      biodegradable polymers, which are expected to improve safety and
      manufacturability. To make biodegradable polymer microneedles with sharp tips,
      micro-electromechanical masking and etching were adapted to produce beveled- and
      chisel-tip microneedles and a new fabrication method was developed to produce
      tapered-cone microneedles using an in situ lens-based lithographic approach. To
      replicate microfabricated master structures, PDMS micromolds were generated and a
      novel vacuum-based method was developed to fill the molds with polylactic acid,
      polyglycolic acid, and their co-polymers. Mechanical testing of the resulting
      needles measured the force at which needles broke during axial loading and found
      that this failure force increased with Young's modulus of the material and needle
      base diameter and decreased with needle length. Failure forces were generally
      much larger than the forces needed to insert microneedles into skin, indicating
      that biodegradable polymers can have satisfactory mechanical properties for
      microneedles. Finally, arrays of polymer microneedles were shown to increase
      permeability of human cadaver skin to a low-molecular weight tracer, calcein, and
      a macromolecular protein, bovine serum albumin, by up to three orders of
      magnitude. Altogether, these results indicate that biodegradable polymer
      microneedles can be fabricated with an appropriate geometry and sufficient
      strength to insert into skin, and thereby dramatically increase transdermal
      transport of molecules.

PMID- 15866335
TI  - Mucosal delivery of microparticle encapsulated ESAT-6 induces robust cell
      mediated responses in the lung milieu.
AB  - ESAT-6 from Mycobacterium tuberculosis is an important T-cell antigen for cell
      mediated immunity in the early phase of tuberculosis infection. Since the lung is
      the organ in which infection is initiated, immune responses in the lung play a
      significant role in restricting the initial infection with M. tuberculosis. The
      aim of the present study was to assess whether efficient cell-mediated immune
      responses in the lung and draining mediastinal lymph nodes could be stimulated by
      pulmonary administration of ESAT-6 encapsulated in poly(lactide) (PLA)
      microspheres. BALB/c mice were immunised intranasally on days 1, 28 and 56 with 2
      microg microencapsulated ESAT-6. Cellular responses in the lungs, spleen and
      mediastinal lymph nodes (MLN) were characterised using ELISPOT and proliferation
      assays. Fluorescence activated cell sorting (FACS) was used to assess the
      expression of CD44 on CD4+ and CD8+ cells derived from the MLN of immunised
      animals. For comparison, groups of mice were immunised intranasally with soluble
      'free' ESAT-6 or intramuscularly with ESAT-6 in Alhydrogel. Intranasal
      instillation of microencapsulated ESAT-6 induced greatest numbers of ESAT-6
      specific IFN-gamma and IL-4 secreting cells in the lung and MLN (P<0.05).
      Similarly, ESAT-6 specific recall responses were strongest following intranasal
      immunisation of mice with microsphere encapsulated antigen (P<0.05). FACS
      demonstrated a higher proportion of T cells expressing CD44 in the MLN from mice
      immunised intranasally with microencapsulated ESAT-6. These data support the
      notion that the immune system is compartmentalised and responses are often
      strongest in compartments proximal to the site of vaccine application.
      Furthermore, our data indicate that, for efficient activation of cell-mediated
      responses, antigens must be presented to the immune system in an appropriate
      formulation.

PMID- 15866336
TI  - Novel sustained release microspheres for pulmonary drug delivery.
AB  - A novel process for generating sustained release (SR) particles for pulmonary
      drug delivery is described. High purity nanoparticles of a hydrophilic, ionised
      drug are entrapped within hydrophobic microspheres using a spray-drying approach.
      Sustained release of the model drug, terbutaline sulphate (TS), from the
      microspheres was found to be proportional to drug loading and phospholipid
      content. Microspheres with a 33% drug loading exhibited sustained release of
      32.7% over 180 min in phosphate buffer. Release was not significantly different
      in simulated lung fluids. No significant burst release was observed which
      suggested that nanoparticles were coated effectively during spray-drying. The
      absence of nanoparticles at the microsphere surface was confirmed with confocal
      microscopy. The sustained release microspheres were formulated as a carrier-free
      dry powder for inhalation, and exhibited a favourable Fine Particle Fraction
      (FPF) of 46.5+/-1.8% and Mass Median Aerodynamic Diameter (MMAD) of 3.93+/-0.12
      microm.

PMID- 15866337
TI  - Influence of the physicochemical properties of liposomes on the accelerated blood
      clearance phenomenon in rats.
AB  - We have recently reported that PEGylated liposomes (PL) are cleared rapidly from
      the blood circulation when they are administered twice in the same rat at certain
      intervals, even if the liposomes are sterically stabilized by a surface
      modification with PEG (referred to as the accelerated blood clearance (ABC)
      phenomenon, J. Control. Release, 88, 35-42 (2003)). Now we report on the
      influence of physicochemical properties (PEG-modification, size and surface
      charge) of either the first or the second dose of liposomes on the ABC
      phenomenon. When, for the first dose, conventional liposomes (CL; without a PEG
      coating) of 110-nm diameter were injected, only a very slight ABC phenomenon was
      observed, irrespective of the liposomal surface charge: both clearance rate and
      hepatic accumulation of the second injected PL were only slightly enhanced
      compared to those of a single dose of PL. Interestingly, when for the first
      injection small-size liposomes (60 nm) were used, either charged or PEG-modified,
      but not neutral, the ABC phenomenon was clearly manifest. Apparently, the
      induction of the ABC phenomenon is not only determined by the PEG coating but
      also by the size and surface charge of the first dose of liposomes. Also when for
      the second dose small-size PEGylated liposomes were used, the ABC phenomenon was
      observed after induction by a first injection of PL, whereas plasma kinetics and
      organ uptake of a second dose of negatively charged CL (NCL, 110 nm) or small
      sized NCL (SNCL, 60 nm) were not altered. Apparently, the PEG coating on the
      second dose is essential for the liposomes to be susceptible to the ABC
      phenomenon. The results reported here suggest that the physicochemical properties
      of both the first and second dose of liposomes are important either for the
      induction of the phenomenon or for its expression. Our observations may have a
      considerable impact on the clinical application and engineering of liposomal
      formulations for use in multiple drug therapy.

PMID- 15866338
TI  - Liposome-encapsulated vincristine, vinblastine and vinorelbine: a comparative
      study of drug loading and retention.
AB  - A comparative study of the loading and retention properties of three structurally
      very closely related vinca alkaloids (vincristine, vinorelbine and vinblastine)
      in liposomal formulations has been performed. All three vinca alkaloids showed
      high levels of encapsulation when accumulated into egg sphingomyelin/cholesterol
      vesicles in response to a transmembrane pH gradient generated by the use of the
      ionophore A23187 and encapsulated MgSO4. However, despite the close similarities
      of their structures the different vinca drugs exhibited very different release
      behavior, with vinblastine and vinorelbine being released faster than vincristine
      both in vitro and in vivo. The differences in loading and retention can be
      related to the lipophilicity of the drugs tested, where the more hydrophobic
      drugs are released more rapidly. It was also found that increasing the drug-to
      lipid ratio significantly enhanced the retention of vinca alkaloids when the
      ionophore-based method was used for drug loading. In contrast, drug retention was
      not dependent on the initial drug-to-lipid ratio for vinca drugs loaded into
      liposomes containing an acidic citrate buffer. The differences in retention can
      be explained on the basis of differences in the physical state of the drug inside
      the liposomes. The drug-to-lipid ratio dependence of retention observed for
      liposomes loaded with the ionophore technique may provide a way to improve the
      retention characteristics of liposomal formulations of vinca drugs.

PMID- 15866339
TI  - Folate targeting of drug carriers: a mathematical model.
AB  - The binding of folate-targeted drug carriers to a receptor-bearing cell surface
      is modeled using a deterministic approach. The model accounts for the presence of
      multiple folate ligands on the carrier surface, the anchoring and presentation of
      the ligands on flexible polymeric tethers, and the combination of both clustered
      and homogeneous spatial distributions of receptors on the cell surface. The model
      was validated against an experimental system where folate-bearing liposomes were
      used as delivery vehicles to deliver drug to tumor cells in vitro. Unknown
      parameters of the model were then estimated by a least-squares fit to the
      experimental data. A parametric study systematically varying the estimated
      parameters around the best-fit values indicated that the model was sensitive to
      these parameters, lending credence to their estimated values. This study
      indicates that drug uptake is dependent on several factors including the ligand
      number, the exposure time, and carrier concentration. For the specific case of
      folate targeting, the cumulative uptake of folate ligands is important, causing a
      decrease in the carrier uptake rate once a threshold cumulative uptake is
      crossed.

PMID- 15866340
TI  - Methoxypoly(ethylene glycol)-conjugated carboxypeptidase A for solid tumor
      targeting: part I: synthesis and characterization.
AB  - In vivo efficacy of novel anticancer agents has been hindered by the inability to
      deliver effective concentrations of drugs to tumors. The use of macromolecules
      such as antibodies and polymers for enzyme delivery to tumors has revealed that
      catalyzing the conversion of a nontoxic prodrug into its cytotoxic form can
      generate an effective level of cytotoxic agents at tumor sites. This study
      primarily focuses on the synthesis and characterization of methoxypoly(ethylene
      glycol)-modified carboxypeptidase A (CPA) for solid tumor targeting. The
      molecular weight of CPA has been successfully altered from 35 to 40-50 kDa via
      attachment of a defined number of mPEG moieties. Relatively pure mPEG-CPA
      conjugates containing one, two, and three mPEG chains were obtained at
      preparative scale quantities through controlled PEGylation followed by
      fractionation that involved size-exclusion chromatography. An enhancement in
      kinetic properties including k(cat) and k(cat)/K(m) towards hippuryl-L
      phenylalanine (hipp-L-phe) was observed in mPEG-CPA conjugates. An increase in
      the V(m) appeared to be responsible for this enhancement. The attachment of mPEG
      to CPA substantially improved the stability of the enzyme with respect to the
      specific peptidase activity toward the model substrate. This finding is
      particularly important in the development of a novel CPA/methotrexate-alpha
      peptide system in solid tumor chemotherapy.

PMID- 15866341
TI  - A novel enzymatic technique for limiting drug mobility in a hydrogel matrix.
AB  - An oral colon specific drug delivery platform has been developed to facilitate
      targetted release of therapeutic proteins as well as small molecule drugs. A
      simple enzymatic procedure is used to modify the molecular architecture of a
      lightly chemically crosslinked galactomannan hydrogel as well as a model drug
      galactomannan oligomer conjugate, fluoroisocynate (FITC) tagged guar oligomer, to
      entrap the model drug. The enzyme-modified hydrogel retains the drug until it
      reaches the colonic environment where bacteria secrete enzymes (namely beta
      mannanase) to degrade the gel and release the drug molecule. Laser scanning
      confocal microscopy combined with fluorescence recovery after photobleaching is
      used to quantify the diffusion of the drug conjugate. The diffusion coefficient
      of solutes in the lightly crosslinked galactomannan hydrogel is approximately
      equal to the diffusion coefficient in the guar solution for simple diffusional
      drug loading. After drug loading, alpha-galactosidase treatment generates
      additional physical crosslinks in the hydrogel matrix as well as between the drug
      oligomer conjugate and the hydrogel, which reduces diffusion of the drug-oligomer
      conjugate significantly. Degradation of the hydrogel by beta-mannanase results in
      a slow and controlled rate of FITC-guar oligomer diffusion, which generates an
      extended release profile for the model drug.

PMID- 15866342
TI  - Methoxypoly(ethylene glycol)-conjugated carboxypeptidase A for solid tumor
      targeting: part II: pharmacokinetics and biodistribution in normal and tumor
      bearing rodents.
AB  - We have evaluated effects of mPEG modification on pharmacokinetic properties of
      carboxypeptidase A (CPA) in normal rats. Attachment of two or three mPEG chains
      to CPA resulted in the generation of mPEG2-CPA and mPEG3-CPA analogs with
      significantly enhanced plasma half-lives, especially during the distribution
      phase. Moreover, the assessment of real-time whole-body kinetics in CT26 tumor
      bearing mice showed both mPEG2-CPA and mPEG3-CPA exhibited increased body
      retention at 48 h post-injection. In addition, tumor localization of mPEG3-CPA at
      72 h was visualized and confirmed by fusion of the gamma-scintigraphy and microCT
      data sets. Results from the imaging studies support our hypothesis of a
      correlation between tumor uptake and enhanced circulatory half-life. Tissue
      distribution data indicated the combination of increased tumor extravasation and
      effective renal elimination observed with mPEG2-CPA at 48 h following
      administration led to the highest observed tumor-to-blood ratio of 4.8:1.
      Although the total concentration of mPEG3-CPA accumulated in tumor was higher
      than that of mPEG2-CPA and CPA at predetermined time intervals, a higher tumor-to
      blood ratio was not obtained owing to a higher level of blood activity. Clearly,
      the attachment of an appropriate number of mPEG chains can facilitate tumor
      localization as effectively as can the use of a tumor-specific antibody.

PMID- 15866343
TI  - Chemoprevention of 4-NQO-induced oral carcinogenesis by co-administration of all
      trans retinoic acid loaded microspheres and celecoxib.
AB  - All-trans retinoic acid (atRA) is one of the most potential chemopreventive
      agents for head and neck squamous cell carcinoma (HNSCC). However, the induced
      metabolism of atRA by cytochrome P450s in the liver limits its clinical
      applications. To overcome such limitation, we had developed atRA-loaded
      microspheres designed to release atRA for a long period. Unfortunately, the atRA
      loaded microspheres severely induced inflammatory responses: that is, atRA
      released from the microspheres significantly induced the proliferation of
      fibroblasts and collagen deposition, thereby causing a permeability barrier for
      drugs from entering the blood stream. In the present study, the effects of
      celecoxib as an anti-inflammatory drug are investigated when it is concurrently
      used with atRA-loaded microspheres to treat 4-NQO-induced oral carcinogenesis. We
      investigated if it might influence the plasma concentration of atRA and its
      metabolism by preventing the fibroblast proliferation and collagen deposition,
      reduce the toxicity level of atRA, and improve the chemopreventive efficacy of
      atRA-loaded microspheres. The concurrently administered celecoxib prevented
      inflammatory responses and suppressed the number of fibroblasts and collagen
      deposition in the fibrous capsules for 14 days. The atRA concentration in plasma
      was also increased and the metabolism of atRA was significantly decreased within
      2 weeks. In the 4-NQO-induced oral carcinogenesis study, the incidence of
      invasive SCC was above 44% when F344 rats were treated with atRA-loaded
      microspheres. However, the treatment using atRA-loaded microspheres and celecoxib
      concurrently could reduce the incidence of invasive SCC up to 28%, and three of
      25 rats were found to have no tongue lesions. In conclusion, the concurrent use
      of celecoxib could maintain the atRA concentration in plasma at a higher level
      while reducing its metabolism by preventing inflammatory responses, thereby
      improving their chemopreventive effects against 4-NQO-induced oral
      carcinogenesis.

PMID- 15866344
TI  - In vitro and in vivo characterization of a novel biocompatible polymer-lipid
      implant system for the sustained delivery of paclitaxel.
AB  - Recently, a novel chitosan-based implantable formulation (chitosan-ePC) was
      developed to provide controlled, local release of paclitaxel (PTX) for the
      treatment of ovarian tumors. Hence, the objective of this study was to evaluate
      this delivery system in vitro in human ovarian SKOV-3 cells and in vivo in mice
      with intraperitoneal implants of drug-free or 14C-PTX-chitosan-ePC films. In
      vitro, 14C-PTX-chitosan-ePC implants (10 mg) provided zero-order constant release
      of 0.92+/-0.03 pg/day PTX over 5 days. Released PTX retained dose-dependent
      activity; effectively inhibiting SKOV-3 proliferation with an ED50 of 211 ng/ml
      of released PTX. Drug-free implants did not affect cell viability or cell
      morphology of SKOV-3 cells. A sustained, zero-order release of PTX was also seen
      in vivo over a 2 week period in mice implanted with 14C-PTX-chitosan-ePC films.
      Correlations between the in vitro and in vivo release of PTX was highly
      significant (R2 = 0.975). After 2-4 weeks, mice with chitosan-ePC implants did
      not demonstrate any signs of encapsulation, inflammation or infection. Overall,
      our in vitro and in vivo results demonstrated zero-order drug release and
      biocompatibility of the novel chitosan-ePC film. This indicates potential
      usefulness of chitosan-ePC implants in the sustained and local delivery of anti
      neoplastic agents.

PMID- 15866345
TI  - Preformed microcapsules for loading and sustained release of ciprofloxacin
      hydrochloride.
AB  - A novel pathway for ciprofloxacin hydrochloride delivery system based on
      spontaneous deposition mechanism was introduced with respect to encapsulation,
      quantitative drug loading and sustained release. Layer-by-layer assembly of
      oppositely charged polyelectrolytes onto melamine formaldehyde (MF) colloidal
      particles, followed by removal of the cores at low pH has yielded hollow
      microcapsules having a unique property to induce spontaneous deposition of
      various water-soluble substances. Observations under scanning electron
      microscopy, atomic force microscopy and transmission electron microscopy provided
      direct proofs of the spontaneous deposition. The quantitative drug loading and
      sustained release properties were elucidated. Results show that the loaded drug
      is proportional to drug feeding concentrations, temperature and salt
      concentrations, demonstrating tailorable deposition behavior that is crucial for
      the drug carrier. The deposited ciprofloxacin hydrochloride could be again
      released in a sustained manner and exhibited a significant antiseptic activity
      with high biocompatibility.

PMID- 15866346
TI  - Ultrasound-mediated gene delivery: kinetics of plasmid internalization and gene
      expression.
AB  - Sonoporation is an approach that can be used to transfer DNA or drugs into cells.
      However, very little is known about the mechanism of ultrasound-mediated membrane
      permeabilization. In this investigation, DNA transport post-sonoporation and the
      subsequent plasmid internalization and protein expression kinetics have been
      studied. Using a plasmid encoding for the green fluorescent protein (GFP),
      labelled or not with an intercalating agent (YOYO-1), it was found that, as
      compared to lipofection that requires endocytosis, sonoporation allowed a rapid
      and direct transfer of naked DNA into the cell cytoplasm probably via ultrasound
      induced pores in the membrane. The kinetics of protein expression were
      significantly faster for sonoporation than for lipofection, the mechanism of
      which requires endocytosis. However, unprotected DNA in the cytoplasm could be
      degraded by resident cytosolic DNases, thereby decreasing ultrasound-mediated
      gene delivery efficiency.

PMID- 15866347
TI  - Plasma membrane poration induced by ultrasound exposure: implication for drug
      delivery.
AB  - Sonoporation, in the presence of ultrasound contrast agents (UCA), is a technique
      that permits the transfer of drugs, including genes, into cells. In this study,
      the size of the pores created by ultrasound application, and the duration of pore
      opening, have been characterized via indirect molecular probing and microscopic
      observation. Internalization of molecules with diameters up to 37 nm was
      efficient and generally well-tolerated; on the other hand, confocal microscopy
      revealed that 75 nm particles entered only a few cells when sonoporation was
      applied. In general, the larger the species to internalize, the poorer the
      transfer. Direct visualization of pores following insonification, using scanning
      electron microscopy, was hampered by the presence of numerous villi on the
      surface of the cells employed (MAT B III), and by the short duration of pore
      opening. Clearer observations of porated regions were possible using red blood
      cells. This research (i) confirms that sonoporation is a means with which to
      achieve macromolecule delivery into cells, and (ii) characterizes in some detail
      the phenomenon of ultrasound induction of transient pores in the cell membrane.

PMID- 15866348
TI  - Target-specific gene silencing by siRNA plasmid DNA complexed with folate
      modified poly(ethylenimine).
AB  - A target-specific delivery system of green fluorescent protein (GFP) small
      interfering RNA (siRNA) plasmid DNA was developed by using folate-modified
      cationic polyethylenimine (PEI). A GFP siRNA plasmid vector (pSUPER-siGFP), which
      inhibits the synthesis of GFP, was constructed and used for suppressing GFP
      expression in folate receptor over-expressing cells (KB cells) in a target
      specific manner. A PEI-poly(ethylene glycol)-folate (PEI-PEG-FOL) conjugate was
      synthesized as a pSUPER-siGFP plasmid gene carrier. KB cells expressing GFP were
      treated with various formulations of pSUPER-siGFP/PEI-PEG-FOL complexes to
      inhibit expression of GFP. The formulated complexes were characterized under
      various conditions. Their GFP gene inhibition and cellular uptake behaviors were
      explored by confocal microscopy and flow cytometry analysis. pSUPER-siGFP/PEI-PEG
      FOL complexes inhibited GFP expression of KB cells more effectively than pSUPER
      siGFP/PEI complexes with no folate moieties and showed far reduced extent of
      inhibition for folate receptor deficient cells (A549 cells). The results
      indicated that folate receptor-mediated endocytosis was a major pathway in the
      process of cellular uptake, suggesting that targeted delivery of siRNA vector
      could be achieved to a specific cell.

PMID- 15866349
TI  - Role of brain-derived neurotrophic factor in eating disorders: recent findings
      and its pathophysiological implications.
AB  - Eating disorders, which include anorexia nervosa (AN) and bulimia nervosa (BN),
      are disorders characterized by abnormal patterns of weight regulation and eating
      behaviors, and by disturbances in attitudes and perceptions toward weight and
      body shape. Brain-derived neurotrophic factor (BDNF) plays a critical role in
      regulating neural survival, development, function, and plasticity in the brain.
      Recent findings using heterozygous BDNF (+/-) knock-out (reduced BDNF levels)
      mice have provided evidence that BDNF plays a role in regulating eating
      behaviors. Recently, we found that serum levels of BDNF in patients with eating
      disorders are significantly decreased compared with normal controls. In addition,
      an association between the BDNF gene polymorphism and eating disorders has been
      demonstrated. We reviewed the role of BDNF in the pathophysiology of eating
      disorders and the BDNF gene as a susceptibility gene for eating disorders.
      Considering the low levels of BDNF in patients with eating disorders, using drugs
      that increase the BDNF levels and/or BDNF gene therapy are possible novel
      therapeutic approaches. Providing confirmation that the BDNF gene is the true
      susceptibility gene for eating disorders could lead to rapid therapeutic progress
      in treating these disorders. In addition, a more complete understanding of the
      signal transduction pathway via the p75 neurotrophin receptor (p75NTR) and TrkB
      receptors would provide new perspectives for treating eating disorders.

PMID- 15866350
TI  - The effects of chronic ethanol consumption and withdrawal on passive avoidance
      task and serum cholinesterase level in rats.
AB  - The effects of chronic ethanol consumption and ethanol withdrawal on serum
      cholinesterase (ChE) activity and passive avoidance task in rats were
      investigated. Ethanol was administered to rats by a modified liquid diet with
      4.8% (v/v) ethanol for 3 days followed by 25 days on a liquid diet in which the
      ethanol concentration was increased to 7.2%. Control rats were pair fed with an
      isocaloric liquid diet not containing ethanol. ChE activity and blood ethanol
      concentration were measured at the end of the 4.8% ethanol consumption and after
      25 days of ethanol (7.2%) feeding and, just before and 24th and 72nd h of ethanol
      withdrawal period. Passive avoidance acquisition was evaluated for 150 s (cut-off
      time) in three individual groups of ethanol-administered, ethanol withdrawn (24th
      and 72nd h of withdrawal) and control rats. Locomotor activity of the rats was
      also measured and evaluated. The daily ethanol consumption of the rats ranged
      from 11.5 to 14.9 g/kg. ChE activities of the ethanol feeding rats were
      significantly increased as compared to control rats at the 3rd (4.8% ethanol) and
      25th days of chronic ethanol (7.2%) consumption and 24th h of ethanol withdrawal.
      It returned to control values at the 72nd h of the withdrawal. Blood ethanol
      levels were measured as 200 and 2.2 mg/dl at just before ethanol withdrawal and
      24th h of ethanol withdrawal, respectively. Both chronic ethanol consumption and
      late period of ethanol withdrawal produced some significant decreases in passive
      avoidance latency of the rats. Our results suggest that chronic ethanol
      consumption and late period of ethanol withdrawal may be related to impairment of
      passive avoidance task in rats. In addition, serum ChE levels do not seem to be
      involved in impairment of cognitive functions in ethanol dependent-rats.

PMID- 15866351
TI  - Body mass index (BMI) in newly admitted child and adolescent psychiatric
      inpatients.
AB  - INTRODUCTION: Obesity is a major problem among children and adolescents suffering
      from chronic mental illness. State-of-the-art measures such as body mass index
      (BMI) and growth-related weight charts are now readily available to clinicians
      and investigators interested in psychotropic drug-associated weight gain in the
      pediatric population. However, no reports that utilize such measures in large
      series of children and adolescents with psychiatric disorders are available.
      METHODS: The authors employed the Nutstat module of the Centers for Disease
      Control and Prevention (CDC) Epi Info software to assess BMI in a psychiatry
      inpatient child and adolescent population in Central Virginia. The authors also
      developed a scoring system to relate psychotropic administration to BMI. RESULTS:
      Children and adolescents with chronic mental illness had greater BMI measurements
      than the general pediatric population. Our scoring system found a relationship
      between antipsychotic drug administration and increased BMI that almost reached a
      level of significance (p=0.062). CONCLUSIONS: The present methodology using
      absolute weight to assess psychotropic drug-associated increase in body weight
      for children and adolescents is unsatisfactory. The authors offer a new and
      convenient methodology to correct this problem.

PMID- 15866352
TI  - Cost analysis of treating schizophrenia with amisulpride: naturalistic mirror
      image study.
AB  - The aim of the study was to examine the costs of schizophrenia treatment using
      the atypical antipsychotic amisulpride relative to treatment with other
      antipsychotics. Service use data were collected for one year of amisulpride
      treatment. The patients were also assessed with the Global Assessment of
      Functioning (GAF) scale and scales of Quality of Life. These were compared with
      retrospectively collected data for the 1-year period prior to the patients
      commencing amisulpride. The findings indicate that, compared with the year
      before, the clinical and quality of life scores improved during the year of
      treatment with amisulpride. There was a numerical reduction of total costs, as
      well as costs of in- and out-patient service use per patient per year during the
      year on amisulpride compared with the year before the patients started
      amisulpride. Patients on amisulpride spent fewer days as acute in-patients, but
      stayed longer in rehabilitation wards. Amisulpride treatment may lead to a
      reduction in the cost of treating schizophrenia in comparison with treatment with
      other antipsychotic medications.

PMID- 15866353
TI  - Diabetes mellitus in patients with schizophrenia in Taiwan.
AB  - A higher prevalence of diabetes mellitus (DM) has been reported in schizophrenic
      patients for decades. But the risk factors for diabetes in these patients were
      not well understood. The aim of our study is to establish the prevalence of DM in
      patients with schizophrenia in Taiwan and discover the risk factors associated
      with it. In 246 recruited schizophrenic patients, the prevalence of DM was 9.8%,
      not significantly different from that of the general population in Taiwan.
      However, we found a significantly higher prevalence of DM in younger
      schizophrenic patients (p=0.001) than in the general population, but not in older
      patients (p>0.10). Our results showed old age, a longer duration of illness,
      obesity, and having a family history of DM were independent factors associated
      with DM in schizophrenia. These results suggest that schizophrenia may make young
      people more vulnerable to developing DM. Further large-scale, controlled studies
      should be done to confirm our results.

PMID- 15866354
TI  - Higher cortisol levels in spring and fall in patients with major depression.
AB  - BACKGROUND: Multiple lines of evidence suggest that there are seasonal effects on
      mood and behavior, and that these effects are related to serotonergic and
      hypothalamic-pituitary-adrenal (HPA) function. This study sought to determine
      whether there is a seasonal effect on clinical parameters, baseline cortisol and
      prolactin levels, and cortisol and prolactin responses to fenfluramine
      administration in subjects with major depression. METHODS: In all, 136 subjects
      with major depression entered the study. Sixty-two subjects who had a major
      depressive episode (MDE) in Spring or in Fall (the Spring/Fall group) were
      compared to 74 subjects who had MDE in Winter or in Summer (the Winter/Summer
      group). Demographic and clinical parameters were assessed and recorded. Clinical
      parameters included depression, aggression, impulsivity, hopelessness, hostility,
      and current suicide ideation rating scales, suicide attempt status, and number
      and maximum lethality of suicide attempts. Cortisol and prolactin levels were
      drawn before fenfluramine administration and hourly for 5 h thereafter. Cortisol
      and prolactin levels were computed as the area under the curve of hourly cortisol
      measurements. RESULTS: Baseline cortisol levels were significantly higher in the
      Spring/Fall group compared to the Winter/Summer group (14.1+/-4.5 ng/ml vs.
      12.5+/-4.4 ng/ml, df=132, t=2.16, p=0.03). There were no seasonal effects on
      baseline prolactin levels, or post-challenge cortisol and prolactin levels.
      CONCLUSIONS: The Spring/Fall group and the Winter/Summer group may represent
      different subtypes of major depression. Future studies need to both confirm our
      results and elucidate the mechanism of the circannual effect on biological
      function in depressed patients. The results of our study underline the importance
      of considering seasonality in psychobiology.

PMID- 15866355
TI  - Schizophrenia and second language acquisition.
AB  - Language acquisition involves brain processes that can be affected by lesions or
      dysfunctions in several brain systems and second language acquisition may depend
      on different brain substrates than first language acquisition in childhood. A
      total of 16 Russian immigrants to Israel, 8 diagnosed schizophrenics and 8
      healthy immigrants, were compared. The primary data for this study were collected
      via sociolinguistic interviews. The two groups use language and learn language in
      very much the same way. Only exophoric reference and blocking revealed meaningful
      differences between the schizophrenics and healthy counterparts. This does not
      mean of course that schizophrenia does not induce language abnormalities. Our
      study focuses on those aspects of language that are typically difficult to
      acquire in second language acquisition. Despite the cognitive compromises in
      schizophrenia and the manifest atypicalities in language of speakers with
      schizophrenia, the process of acquiring a second language seems relatively
      unaffected by schizophrenia.

PMID- 15866356
TI  - Effects of olanzapine on auditory P300 and mismatch negativity (MMN) in
      schizophrenia spectrum disorders.
AB  - We investigated effects of olanzapine (5-10 mg/day) on passive and active
      attention in 11 patients with schizophrenia spectrum disorders and 15 healthy
      controls by using auditory evoked potentials (AEPs) mismatch negativity (MMN) and
      P300. AEPs were elicited during active and passive auditory "oddball" paradigms
      before, after 2 weeks and 4 weeks of olanzapine treatment. Baseline P300
      amplitudes, but not MMN, were significantly reduced in patients compared with
      controls. Although clinical signs improved significantly measured by Positive and
      Negative Syndrome Scale (PANSS), olanzapine had no significant effects on
      latencies and amplitudes of MMN and P300. Thus, olanzapine does not have effects
      on active and passive attention in patients with schizophrenia spectrum
      disorders. Four weeks olanzapine treatment may be insufficient for the
      improvement of cognitive dysfunction in terms of inability to focus on relevant
      stimuli in these patients.

PMID- 15866357
TI  - Influences of caffeine, acetazolamide and cognitive stimulation on cerebral blood
      flow velocities.
AB  - Assessment of cerebral blood flow velocities (CBFV) can be used as a non-invasive
      tool to evaluate specific drug effects, like caffeine (CAF), acetazolamide (AA)
      as well as cognition. Their influences on each others CBFV were evaluated in
      detail, using a randomized, double-blind, double-dummy, placebo-controlled three
      fold cross-over study design in 18 right-handed healthy male volunteers. CBFV
      (maximal, mean, minimal) and pulsatility index of both middle cerebral arteries
      were recorded by transcranial Doppler ultrasound simultaneously, during a verbal
      memory test, oral CAF, intravenous AA or placebo. AA led to increase in CBFV of
      25-32%. Caffeine resulted in decreased V(mean) and V(min) of 10-13%. Cognitive
      stimulation resulted in a slight increase of CBVF of about 4%, but was overruled
      by effects of AA and CAF. We conclude that pharmacological effects can easily be
      assessed by TCD during clinical pharmacological studies of vasoactive drugs.
      However intraindividual variability and effects of neuropsychological stimulation
      needs to be taken into account.

PMID- 15866358
TI  - Acute neurophysiological effects of the hypnotic zolpidem in healthy volunteers.
AB  - INTRODUCTION: The imidazopyridine zolpidem is a hypnotic drug with relative
      selectivity for the benzodiazepine (BZP) type 1 receptor subtypes displaying a
      different biochemical structure to that of BZPs. Little is known of its
      electrophysiological effects. PURPOSE: The aim of the present study was to
      investigate the acute neurophysiological effects of clinical oral doses of
      zolpidem. METHODS: This was a double blind, independent group design study.
      Thirty-six young, healthy volunteers were randomly allocated to one of three
      groups--zolpidem (5 mg and 10 mg) and placebo. In addition to ERPs, behavioural
      measures were used to examine sedative effects of the drug. RESULTS: ERPs were
      affected in a similar way to that described after sedative/hypnotic drug
      ingestion: increased N2 and P3 latencies and decreased N2 and P3 amplitudes.
      However, contrary to what is expected of a hypnotic drug, there was no change
      with N1 while P2 amplitude increased after the highest dose. CONCLUSIONS: Because
      zolpidem showed different effects in different components, it seems to first
      enhance or preserve initial orienting (no change in N1), after an increase of P2
      and then drastically diminish resource allocation (affecting N2 and P3 latencies
      and amplitudes). The study with ERPs, therefore, allows a more direct "moment to
      moment" investigation of finer mechanisms of changes in cerebral processes
      underlying the acute ingestion of the drug in question. The effects on N2 and P3
      amplitudes and latencies were similar to those of other sedative/hypnotic drugs.
      However, zolpidem led to an unexpected increase in P2 amplitude; this effect may
      be related to its selective receptor binding profile and warrants further
      research.

PMID- 15866359
TI  - Effects of antidepressant treatment and of gender on serum leptin levels in
      patients with major depression.
AB  - Leptin is a product of the obese gene and plays an important role in the
      regulation of body weight and food intake. Weight and appetite are frequently
      altered in depression. So far, inconsistent results have been reported in terms
      of leptin levels in depression. Therefore, the authors investigated serum leptin
      levels in patients with depression and in healthy controls, and whether there was
      any alteration throughout antidepressant treatment. Female patients showed
      significantly higher leptin levels than those of the control females both before
      and after the response to antidepressant treatment, whereas no difference was
      found between the male patients and the male controls. The improvement from
      depression with antidepressant treatment caused a further elevation on the leptin
      levels, in both female and male patients. These findings confirm an increase in
      leptin levels in depressive patients and presence of a sexual dimorphism.
      Moreover, clinical response to antidepressant treatment seems to have an
      additional increasing effect on leptin levels.

PMID- 15866360
TI  - A comparative study with two types of elevated plus-maze (transparent vs. opaque
      walls) on the anxiolytic effects of midazolam, one-trial tolerance and fear
      induced analgesia.
AB  - The phenomenon known as one-trial tolerance (OTT) to the anxiolytic effects of
      benzodiazepines observed in rats submitted to the elevated plus-maze test (EPM)
      is considered to be due to the emergence of phobic states across the test/retest
      sessions. Antinociception is a usual component of the defense reaction. Until
      now, no study has examined antinociception and OTT together in freely behaving
      rats in the EPM. This work is a new approach looking at the sensorimotor gatings
      underlying OTT through the examination of the changes in reactivity to noxious
      stimuli during OTT development. We used the tail-flick test to assess the
      reactivity of rats to noxious stimulus during the effects of midazolam in
      test/retest sessions using two types of EPM, one with opaque (standard EPM) and
      another one with transparent walls (modified EPM). The authors had previously
      shown that this modified test caused an overall stressful situation more related
      to anxiety while the standard test coursed with a mixture of anxiety and high
      fear levels. In both plus mazes, the study was conducted in two experiments: (i)
      midazolam before the first trial, and (ii) midazolam before the second trial. In
      each experimental condition the effects of midazolam were tested under two doses
      (0.5 and 1.0 mg/kg) against a control group that received injections of saline.
      The anxiolytic effects of midazolam were more pronounced in animals tested in the
      modified EPM than in the standard EPM. Stressful stimuli present in both types of
      maze were able to elicit one-trial tolerance to midazolam on re-exposure.
      However, anxiolytic-insensitive behaviors in the first and the reduction in
      exploratory activity in the second trial are more pronounced in the standard EPM
      indicating that this test is more prone to transfer fear-related states across
      trials than the modified maze test. Antinociception is not present upon the re
      exposure of rats to the EPM. These findings show that animals tested in the
      modified EPM showed higher sensitivity to the anxiolytic effects of midazolam
      than the standard EPM. Antinociception was not a concomitant of the shift in the
      emotional state present in the retest sessions of the EPM. These results are in
      agreement with the premises that repeated stressful experience leads to
      anxiolytic-insensitive fear state different from anxiety.

PMID- 15866361
TI  - Nicotine and clozapine actions on pre-pulse inhibition deficits caused by N
      methyl-D-aspartate (NMDA) glutamatergic receptor blockade.
AB  - Pre-pulse inhibition (PPI) is a phenomenon of neurobehavioral plasticity in which
      the motor response to a startling stimulus is inhibited by a preceding stimulus
      of a lower intensity. Most often this is tested in the auditory mode. PPI is
      impaired in a variety of clinical states, most notably schizophrenia. PPI is
      easily modeled in experimental animals and serves as a useful basis for
      determining the neural bases for behavioral plasticity. In the current study we
      examined the interactions of N-methyl-D-aspartate (NMDA) glutamate and nicotinic
      cholinergic receptor systems in the expression of PPI. Female Sprague-Dawley rats
      were tested for auditory PPI after s.c. injections of the NMDA antagonist
      dizocilpine (also known as MK-801), the prototypic nicotinic agonist nicotine or
      both. Vehicle (saline) injections served as the control. Nicotine (0.2-0.8 mg/kg)
      by itself caused a modest but significant dose-related improvement in PPI.
      Dizocilpine (25-100 microg/kg) caused a dramatic dose-related impairment in PPI.
      Interestingly, the low to moderate doses of nicotine potentiated the PPI
      impairment by dizocilpine. In a second experiment nicotine and dizocilpine
      interactions with the atypical antipsychotic drug clozapine were assessed. As in
      the first experiment, nicotine potentiated the adverse effects of dizocilpine on
      PPI. The combination of nicotine with clozapine effectively attenuated the PPI
      impairment caused by dizocilpine when neither alone was effective. Inasmuch as
      PPI is impaired in schizophrenia, its reversal by the antipsychotic drug
      clozapine may depend on co-administration of nicotine by smoking in the patients.
      Development of nicotinic-based co-treatments for schizophrenia may achieve this
      benefit of nicotine without the hazards of smoking. Sensory modulation deficit,
      which is a syndrome of sensory over-responsiveness may also benefit from such
      combination therapy.

PMID- 15866362
TI  - Optimized voxel-based morphometry of gray matter volume in first-episode,
      antipsychotic-naive schizophrenia.
AB  - This study examined gray matter (GM) volume abnormalities in first-episode,
      antipsychotic-naive Indian schizophrenia patients. Magnetic resonance images of
      18 schizophrenia patients and 18 matched healthy comparison subjects were
      analyzed by optimized voxel-based morphometry. Schizophrenia patients had
      significantly smaller global GM and greater global CSF volumes and smaller
      regional GM volume in superior frontal, inferior frontal, cingulate, post
      central, superior temporal and parahippocampal gyri, inferior parietal lobule,
      insula, caudate nuclei, thalamus and cerebellum. Findings suggest limbic,
      heteromodal cortical, striatal, thalamic and cerebellar abnormalities in
      schizophrenia.

PMID- 15866363
TI  - Psychophysiological differences in schizophrenics with and without delusional
      misidentification syndromes: a P300 study.
AB  - There is a debate on whether delusional misidentification syndromes (DMSs) and
      schizophrenia are distinct disorders. Information-processing deficits have been
      found in both. Since the P300 component of event-related potentials (ERPs)
      reflects attention and working memory (WM) mechanisms, the P300 elicited during a
      WM test was studied in schizophrenic patients with DMS in comparison to
      schizophrenic patients without DMS and controls. Nine schizophrenic patients with
      DMS, 11 without DMS and 11 healthy controls were tested with a computerized
      version of the digit span test of the Wechsler batteries. Auditory ERPs were
      measured during the anticipatory period of the test. P300 amplitude in prefrontal
      areas was found to be significantly reduced in schizophrenics without DMS and
      markedly less in DMS patients compared to controls. P300 latency in the central
      midline brain region was significantly prolonged in DMS patients compared to the
      other groups. Memory performance was significantly reduced in both patient groups
      as compared to healthy controls. The results may indicate abnormalities in both
      allocation of attentional resources and automatic orienting in schizophrenic
      patients with DSM. In contrast, even though schizophrenic patients without DMS
      exhibit partial similarities with patients suffering from DMS, they show
      excessive reduction of P300 amplitude located at the left frontal area. Future
      studies might clarify these issues.

PMID- 15866364
TI  - Severe cognitive impairment correlates with higher cerebrospinal fluid levels of
      lactate and pyruvate in a canine model of senile dementia.
AB  - Diagnosis of dementia of the Alzheimer's type depends on clinical criteria and
      exclusion of other disorders because, at this time, a validated biological
      marker, aside from histological brain examination, remains to be established. The
      canine counterpart of senile dementia of the Alzheimer type (ccSDAT) is
      considered a promising model for examining behavioral, cellular and molecular
      processes involved in early phases of human brain aging and Alzheimer disease
      (AD). In order to investigate the first events taking place in canine cognitive
      dysfunction, in this paper we established a new and rapid behavioral test that
      finely discriminates the degrees of cognitive impairment. Cerebrospinal fluid
      (CSF) analysis was performed to determine the relationship between each disease
      stage and modification of cerebral energy metabolism. Our results demonstrate a
      parallel increase of lactate, pyruvate and potassium concentrations in the severe
      cognitive deficit. These differences are discussed in view of the neuroprotective
      role presently given to lactate.

PMID- 15866365
TI  - Increased midkine levels in sera from patients with Alzheimer's disease.
AB  - Midkine (MK) is a heparin binding growth factor and promotes growth, survival and
      migration of various cells including neurons. It is also known to accumulate in
      senile plaques of patients with Alzheimer's disease (AD). To investigate the
      involvement of serum MK in the pathophysiology of AD, serum MK levels were
      determined in patients with AD (n=36) and age- and sex-matched healthy controls
      (n=32), using an enzyme-linked immunosorbent assay (ELISA). The serum MK values
      of the patients with AD (median 560 and interquartile range (500-755) pg/ml) were
      significantly (U=278.5, P=0.0003, Mann-Whitney U-test) higher than those of the
      controls (median 500 and interquartile range (385-520) pg/ml). Moreover, 17
      patients (47.2%) had abnormally high values of more than 600 pg/ml, but no
      controls (0%) did. There was no correlation between serum MK level and the mini
      mental state examination (MMSE) score in the patients. The demonstration of
      elevated MK levels in sera of patients with AD may contribute toward an
      understanding the pathophysiology of this disease, and provide a novel potential
      therapeutic strategy for decreasing neuronal damages in patients with AD. We
      found that serum MK levels in patients with AD were increased in comparison with
      those of normal controls.

PMID- 15866366
TI  - Obstetric complications in siblings of Japanese schizophrenics: data from the
      Maternal and Child Health Handbook.
AB  - Although the precise etiology of schizophrenia remains unknown, the development
      of schizophrenia has been associated with a history of obstetric complication
      (OC). Furthermore, some studies show structural and functional brain
      abnormalities in the unaffected siblings of schizophrenics. In this study the
      perinatal histories of 18 unaffected siblings of schizophrenics and 15 unrelated
      healthy controls, as detailed in their mothers' Maternal and Child Health
      Handbook records, were retrospectively analyzed. Records were scored for
      obstetric complication by the method developed by [Parnas, J., Schulsinger, F.,
      Teasdale, T.W., Shulsinger, H., Feldman, P.M., Mednick, S.A., 1982. Perinatal
      complications and clinical outcome within the schizophrenia spectrum. Br. J.
      Psychiatry 140, 416-420]. The authors found the sibling group had greater
      pregnancy and birth complication (PBC) frequency, severity and total scores than
      the control population.

PMID- 15866367
TI  - Cognitive functions in prepsychotic patients.
AB  - OBJECTIVE: Cognitive dysfunctions are now widely understood as an essential
      feature of schizophrenia. A great number of cognitive disturbances have been
      described in drug-naive first-episode patients as well. The full-blown psychotic
      symptoms are usually preceded by a longer prodromal period, in which non-specific
      psychological disturbances are already present. The late prodromal phase is also
      coined as the prepsychotic state, with attenuated, isolated psychotic symptoms.
      The aim of the present study was to detect cognitive dysfunctions among young
      adults at the prepsychotic stage with the use of a standardized computer based
      cognitive test battery. METHOD: Eleven (9 men, 2 women) young Hungarian adults
      referred to the Outpatient Clinic of the Department of Psychiatry at the
      University of Debrecen were studied. The patients were re-evaluated for psychotic
      symptoms after 12 months. The patients had no history of psychiatric disorders or
      psychotic episodes and were referred by general practitioners on account of non
      specific emotional or behavioural abnormalities. The subjects were asked to
      perform a series of 13 computerized neuropsychological tests of the Cambridge
      Neuropsychological Test. The performance of the patients were compared to that of
      the standardized database of the Cambridge Neuropsychological Test. RESULTS AND
      DISCUSSION: The performance of the prepsychotic patients was significantly lower
      compared to the healthy individuals in the paired associate learning (PAL,
      p<0.001), Spatial recognition memory (SRM, p<0.05), Rapid visual processing (RVP,
      p<0.05), and Spatial working memory (SWM, p<0.05) tests. CONCLUSION: Cognitive
      deficits were found mainly in attentional, frontal and prefrontal cognitive
      functions. These impairments may be present at the early stages of the
      development of psychosis and the standardized cognitive test battery (CANTAB)
      might be a useful tool for the detection of early cognitive impairments and
      provide a rationale for early intervention in individuals at risk of developing
      psychosis.

PMID- 15866368
TI  - Isolated angiitis of the central nervous system: a case presented with atypical
      psychiatric symptoms.
AB  - Isolated angiitis of the central nervous system (IACNS) is a rare form of
      angiitis limited to the central nervous system. The clinical finding of the
      combined series revealed that headache was the most common symptom within a
      combination of focal and diffuse neurological deficits. The case, a 28-year-old
      man, is presented; the clinical presentation and diagnostic difficulties are
      discussed. The patient's symptoms began with an obvious atypical depression. In
      spite of an antidepressive treatment, his symptoms continued to worsen with
      personality, mood changes and euphoria added to the clinical picture. Meanwhile
      after several transient ischemic attacks, 6 months later, he was admitted with
      neurological symptoms including headache, diplopia, and cerebellar ataxia. The
      radiological investigation was mimicked by primary brain lymphoma. The brain
      biopsy excluding of lymphoma revealed parenchymal hemorrhage with nonspecific
      degenerative changes. In systemic investigation, no underlying cause for
      vasculitis could be found. Neurological but not psychological deficits and
      radiological lesions of the patient improved with steroid therapy. Since we could
      not find features of systemic vasculitis, the patient's lesions responded to
      corticosteroid treatment and neuropathological investigation revealed no
      lymphoma, We concluded that the most probable diagnosis would be IACNS.

PMID- 15866369
TI  - Clozapine-induced tardive dyskinesia: a case report.
AB  - PURPOSE: Clozapine is indicated in the treatment of patients with tardive
      dyskinesia. However, there have been some reports of movement disorders
      associated with clozapine treatment in the literature. The authors report a
      patient who developed tardive dyskinesia 1 year after initiation of clozapine
      treatment. CASE: The patient was a 65-year-old male with diagnosis of
      schizophrenia who had used multiple typical and atypical antipsychotics for 30
      years. Clozapine treatment was initiated for his resistant symptoms. He developed
      buccolingual dyskinesia of moderate severity, which started 1 year after the
      initiation of clozapine treatment and did not ameliorate during follow-up.
      CONCLUSION: This case may contribute to existing knowledge by raising the
      possibility that clozapine can induce dyskinesia.

PMID- 15866391
TI  - Images in resuscitation: bruising after thrombolysis for massive pulmonary
      embolism (PE).

PMID- 15866392
TI  - Resuscitation great: Bjorn Lind--the ground-breaking nurturer.

PMID- 15866393
TI  - Spontaneous subarachnoid hemorrhage and serious cardiopulmonary dysfunction--a
      systematic review.
AB  - INTRODUCTION: : The association between the degree of neurological deficit and
      cardiopulmonary dysfunction in patients with spontaneous subarachnoid hemorrhage
      (SAH) is poorly understood. METHOD: A systematic search (MEDLINE, bibliographies,
      to 9.2004) was performed for prospective studies (any architecture; > or = 10
      patients with SAH), reporting on neurological deficit and cardiopulmonary
      dysfunction. Neurological deficit was graded according to the Hunt-Hess or
      Botterell scores as minimal (1 or 2 points), moderate (3), or severe (4 or 5),
      and tested for an association with cardiopulmonary dysfunction (Chi-square test).
      RESULTS: Relevant data came from two randomized trials, four case control
      studies, and 31 uncontrolled series. In eight studies (386 patients), ECG
      abnormalities were found in 32% of patients with minimal, 55% with moderate, and
      58% with severe neurological deficit (P < 0.0001). In six studies (135),
      echocardiographic abnormalities were found in 4% of patients with minimal, 30%
      with moderate, and 52% with severe neurological deficit (P = 0.0001). In two
      trials (63), creatinine phosphoskinase was increased in 18% of patients with
      minimal, 71% with moderate, and 100% with severe neurological deficit (P <
      0.0001). In three trials (309), troponin-I was increased in 10% of patients with
      minimal, 20% of patients with moderate, and 46% with severe neurological deficit
      (P < 0.0001). In five trials (163), pulmonary edema was found in 4% of patients
      with minimal, 12% with moderate, and 35% with severe neurological deficit (P <
      0.0001). Seventeen studies reported on mortality; 26% of the patients died, 80%
      of deaths were directly related to SAH. CONCLUSIONS: In patients with spontaneous
      SAH, cardiopulmonary dysfunction is more likely to occur with increasing
      neurological deficit.

PMID- 15866394
TI  - The prevalence of recordings of the signs of critical conditions and emergency
      responses in hospital wards--the SOCCER study.
AB  - OBJECTIVE: To estimate the prevalence of recordings in case notes of disturbed
      physiological variables in adult admissions in general hospital wards. DESIGN AND
      SETTING: Retrospective cross-sectional survey of 3160 admissions in general wards
      in five hospitals in a 14-day period. MAIN OUTCOME MEASURES: Recordings of 26
      potential early signs (ES) and 21 potential late signs (LS) of critical
      conditions. Eight late signs were classified as Liverpool Hospital Equivalent
      Calling Signs (LES). RESULTS: 54.7% admissions had at least one recording of
      early signs, 16.0% late signs and 6.4% LES. When ranked in order of recordings
      per 100 admissions, the top five ES were SpO(2) 90-95% (193.7), systolic blood
      pressure (SBP) 80-100 mmHg (85.2), pulse rate 40-49 or 121-140 b/min (32.0), SBP
      181-240 mmHg (23.0) and "Other" (22.1) (mainly breathlessness or temperature > 38
      degrees C). The top five LS were SpO2 < 90% (31.5), pulse rate < 40 or > 140 /min
      (6.6), SBP < 80 mmHg (4.2), GCS < or = 8 (3.8) and unresponsiveness to verbal
      commands (2.4). There were average signs per admission of ES 4.4, LS 0.6 and LES
      0.19. Although there were differences in rates of recordings of signs across the
      five hospitals, the patterns of top 10 most frequent were similar. CONCLUSIONS:
      There was a high incidence of recordings of disturbed physiological variables in
      general ward patients. Changes to hospital emergency response systems to include
      rapidly responding teams to patients with the signs of developing critical
      conditions should be supported by training programmes for ward staff on the early
      recognition and management of patients with the warning signs.

PMID- 15866395
TI  - Staff awareness of a 'Do Not Attempt Resuscitation' policy in a District General
      Hospital.
AB  - UK hospitals have been instructed to ensure that all staff understand the
      institution's resuscitation policy. Using a questionnaire, we determined the
      level of knowledge about the hospital's 'do not attempt resuscitation' (DNAR)
      policy amongst a range of staff. Six hundred and seventy-seven questionnaires
      were returned. 91.4% of responders did not know the correct overall percentage
      survival to hospital discharge following an in-hospital cardiac arrest. 19.3% of
      doctors, 10.6% of nurses, and 8.9% of health care support workers (HCSW) gave
      answers in the correct range (i.e., 15-25%). Most doctors (93.5%), nurses
      (93.5%), and HCSW (78.9%) correctly identified that cardiopulmonary resuscitation
      (CPR) should be the default position, when a DNAR decision does not exist. The
      majority of doctors (78.5%), nurses (73.2%) and HCSW (65.8%) appreciated that the
      hospital policy allowed a senior trainee doctor (specialist registrar; SpR) to
      make the initial decision without consultation with more senior medical staff.
      Knowledge of who was ultimately responsible for the DNAR decision was also good,
      with 100% of doctors, 100% of midwives, 98.3% of nurses and 78.9% of HCSW
      responding correctly. Ten percent of doctors, 15% of nurses and 10.5% of HCSW
      believed that the next of kin could demand resuscitation or a DNAR status. There
      was inconsistency about what information staff felt should be included in DNAR
      documentation and what, if any, continuing care should be given to patients who
      are not for resuscitation. Our study demonstrates that there is room for
      improvement in the awareness of staff about the DNAR process. The local DNAR
      policy is being reviewed to ensure that its messages are clear and a specific
      DNAR educational programme has been commenced.

PMID- 15866396
TI  - Older people's reasoning for resuscitation preferences and their role in the
      decision-making process.
AB  - OBJECTIVES: To investigate older patients' reasoning for their cardiopulmonary
      resuscitation (CPR) preferences and the related decision-making process (DMP).
      METHODS AND SUBJECTS: In a descriptive study 220 elderly home-dwelling
      cardiovascular patients were interviewed and asked to justify their CPR
      preferences according to the given statements. Questions related to DMP were
      asked and their physical function, cognition, mood, and quality of life were
      assessed. RESULTS: Resuscitation preferences were associated with several patient
      characteristics, such as age, mood and quality of life. Patients preferring CPR
      (114/220, 52%) estimated their prognosis of CPR to be better than those
      preferring to forgo CPR. They justified their view: "Life is precious and worth
      living for me" (92%), "Maintaining life is a value of its own" (92%), "I feel
      needed by my family and my closest" (81%). Participants preferring to forgo CPR
      (106/220, 48%) justified: "I have already gained old age and led a full life"
      (88%), "People cannot decide these things" (72%). Only 9% of patients had
      discussed, and 38% would like to discuss preferences for life-sustaining
      treatments (LSTs) with their physician. However, 80% of respondents felt that the
      patients should take some part in the DMP; either alone (9%), together with a
      physician (23%), or together with a physician and a close relative (48%).
      CONCLUSIONS: Older people justify their resuscitation preferences highlighting
      their experiences of meaningful life or fulfillment of their life, interpersonal
      relationships with their loved ones and presumed outcome of CPR. Less than a half
      of the patients wished to discuss CPR and LSTs preferences in their current
      situation with their physician, but nevertheless wanted to participate in the DMP
      of end-of-life treatment. Physicians should assess patients' own preferences in
      depth.

PMID- 15866397
TI  - The effect of topical non-steroidal anti-inflammatory cream on the incidence and
      severity of cutaneous burns following external DC cardioversion.
AB  - INTRODUCTION: Cutaneous burns are a common cause of morbidity following direct
      current (DC) cardioversion. We designed a study to determine whether the
      application of non-steroidal anti-inflammatory cream prior to cardioversion
      reduces their incidence and severity. MATERIALS AND METHODS: Two hours before
      elective DC cardioversion, we randomised 55 patients to receive ibuprofen 5%
      cream or placebo cream over sternal and apical pad sites, with patients acting as
      their own controls. Two hours after cardioversion an independent blinded observer
      measured skin temperature, erythema index, and minimum sensory and pain detection
      thresholds at sternal and apical pad sites. Visual analogue pain score (VAS) for
      each site was recorded at 2 h and 24 h post-cardioversion. RESULTS: There was a
      statistically significant difference between pain measured by VAS, skin
      temperature and pain detection threshold measured at pad sites with pre-applied
      ibuprofen 5% cream and those with pre-applied aqueous cream, after elective DC
      cardioversion. CONCLUSION: Prophylactic application of topical ibuprofen 5% cream
      2h prior to elective DC cardioversion reduces pain and inflammation.
      Consideration should be given to use of prophylactic application of topical
      ibuprofen as routine treatment for elective DC cardioversion.

PMID- 15866398
TI  - The effect of prophylactic topical steroid cream on the incidence and severity of
      cutaneous burns following external DC cardioversion.
AB  - INTRODUCTION: Cutaneous burns are a common cause of morbidity following direct
      current (DC) cardioversion. We designed a prospective double-blinded controlled
      study to determine whether the application of steroid cream prior to
      cardioversion reduces their incidence and severity. MATERIALS AND METHODS: Two
      hours before elective DC cardioversion, we applied betamethasone 0.1% cream or
      placebo cream over sternal and apical pad sites in 56 patients, with patients
      acting as their own controls. Two hours after cardioversion, a separate blinded
      observer measured the visual analogue pain score (VAS), sensory and pain
      detection thresholds, skin temperature and erythema index at sternal and apical
      pad sites. RESULTS: The study had an 80% power to detect a 50% difference in VAS
      at 2 h, accepting an alpha error of 0.05. There was no difference between pain at
      2 or 24 h, skin temperature, erythema index, sensory and pain detection
      thresholds at pad sites treated with steroid cream or control. CONCLUSION:
      Topical betamethasone 0.1% cream applied 2 h before elective DC cardioversion is
      no more effective than placebo at reducing the pain and inflammation from
      cardioversion burns.

PMID- 15866399
TI  - Two-rescuer CPR results in hyperventilation in the ventilating rescuer.
AB  - The "Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency
      Cardiovascular Care--International Consensus on Science" recommend a tidal
      ventilation volume of 10 ml/kg body-weight without the use of supplemental oxygen
      during two-rescuer adult cardiopulmonary resuscitation (CPR). This relates to a
      ventilation volume of about 6.4 l/min. Additionally, the first aid provider
      ventilating the victim will breathe for him/herself during the external chest
      compression period adding another 3.2 l/min of ventilation. Finally, a deep
      breath is recommended before each ventilation to increase the end-expiratory
      oxygen concentration of the air exhaled. To investigate the effects of these
      recommendations, 20 healthy volunteers were asked to perform two-rescuer CPR in a
      lung model connected to a BLS-manikin. End-tidal carbon dioxide, oxygen
      saturation, and heart rate were recorded continuously. Capillary blood gas
      samples were collected and non-invasive blood pressure was recorded prior to the
      start of external chest compressions and immediately after the end of each
      measurement period. Furthermore, hyperventilation related symptoms reported by
      the volunteers were also recorded. The data reveal a significant decrease in
      capillary and end-tidal carbon dioxide pressure in the volunteers (P < 0.001).
      Additionally, in 75% of test persons multiple hyperventilation associated
      symptoms occurred. Ventilation during two-rescuer CPR performed according to the
      Guidelines 2000 may cause injury to the health of first aid providers. To
      minimize hyperventilation, both rescuers should exchange their positions at
      intervals of 3-5 min. These data challenge the recommendation to take a deep
      breath prior to each ventilation.

PMID- 15866400
TI  - Resuscitation of out-of-hospital cardiac arrest by Asian primary health-care
      physicians.
AB  - AIM: To assess the experience, knowledge and attitudes of local primary health
      care doctors towards resuscitation in out-of-hospital cardiac arrest. METHODS: We
      conducted a survey of general practitioners (GPs) working in both private and
      public sectors. The survey consisted of 29 questions and was self-administered.
      RESULTS: Response rate was 78.8% with 66 public practice doctors and 23 from
      private practice. Average ages were 39.8 years (private) and 35.5 years (public)
      with mean years of practice being 15.1 (private) and 11.4 (public). 47.8% of
      private and 69.7% of public doctors had been advanced cardiac life-support (ACLS)
      trained. 13.0% of private and 10.6% of public had witnessed a cardiac arrest in
      their clinics in the past year. 92.3% of public and 26.1% of private doctors had
      defibrillators in their clinics (P < 0.01, OR = 34.0, 95% CI = 9.2-125.2). 83.3%
      (public) versus 52.2% (private) (P < 0.01 OR = 4.6, 95% CI = 1.6-13.0) agreed
      that all clinics should have defibrillators. 59.1% (public) and 34.8% (private)
      would support legislation for defibrillators in clinics (P = 0.04, OR = 2.7, 95%
      CI = 1.01-7.3). Reasons given for not buying defibrillators included 'too
      expensive' (70.6%) and 'unsure how to use' (5.9%). 66.0% would consider buying a
      defibrillator if the cost was less than Singapore 3000 dollars (1400 Euro). 69.6%
      (private) and 63.6% (public) were interested in participating in a GP
      defibrillation project. CONCLUSION: Primary care physicians do see themselves as
      having an important role in resuscitation. We propose a local initiative to
      equip, educate and encourage defibrillation by GPs in our community.

PMID- 15866401
TI  - Sex differences in outcome after ventricular fibrillation in out-of-hospital
      cardiac arrest.
AB  - INTRODUCTION: Previous studies have shown that early defibrillation programs
      improve survival after an out-of-hospital cardiac arrest (OHCA). Reports also
      suggest that women fare worse than men do after cardiovascular events, but there
      is no population-based study of sex differences after an OHCA with early
      defibrillation. We, therefore, compared the short- and long-term survival and
      quality-of-life (QOL) in women and men after an OHCA. METHODS: All patients with
      a ventricular fibrillation (VF) OHCA who received early defibrillation in
      Olmstead County, Minnesota between November 1990 and December 2000 were included.
      Using medical records and the cardiac arrest database, the short- and long-term
      survival and QOL based on a SF-36 survey of each sex were compared. Adjusted QOL
      scores were obtained by using age- and sex-specific norms from a sample of the
      general U.S. population; an adjusted score of 50 (normalized mean) was considered
      normal. RESULTS: Thirty-seven female and 163 male patients presented with a VF
      OHCA and early defibrillation. Survival to hospital admission was significantly
      better for women than men [30 female survivors to admission (81%), 112 male
      (69%), p = 0.04]. Paradoxically, survival to discharge among those admitted was
      worse for women [13 female survivors to discharge (43%), 66 male (61%), p =
      0.04]. The average length of follow-up was 4.8+/-3.0 years. The 5-year expected
      survival was 83% in women and 78% in men (p = 0.48). There was no difference in
      call-to-shock time (6+/-2, 6+/-2 min, p = 0.6) or whether the arrest was
      witnessed (86, 82%, p = 0.64). There was no statistical difference between women
      and men in age (64+/-17, 65+/-14 years), ejection fraction (40+/-17, 40+/-18%),
      diabetes (17, 29%, p = 0.16), hypertension (23, 28%, p = 0.58) or known CAD (27,
      48%, p = 0.06). Adjusted QOL scores were similar between women and men in terms
      of pain (52+/-9, 52+/-10) vitality (47+/-11, 40+/-9), general health (49+/-9,
      44+/-7), social function (51+/-10, 51+/-8), and mental health (50+/-10, 49+/-6).
      CONCLUSION: Women are more likely to survive to hospital admission following an
      OHCA. However, admitted women less likely to survive their hospital stay. Long
      term survival and QOL are equally favorable in both sexes.

PMID- 15866402
TI  - Modified cardiopulmonary resuscitation (CPR) instruction protocols for emergency
      medical dispatchers: rationale and recommendations.
AB  - BACKGROUND: International consensus guidelines now support the use of "chest
      compressions-only" cardiopulmonary resuscitation (CPR) instructions (CCOIs) by
      emergency medical dispatch (EMD) personnel providing telephone assistance to
      untrained bystanders at a cardiac arrest scene. These guidelines are based
      largely on evolving experimental data and a clinical trial conducted in one venue
      with distinct emergency medical services (EMS) system features. Accordingly, the
      Council of Standards for the National Academies of Emergency Dispatch was asked
      to adapt a modified telephone CPR protocol, and specifically one that could be
      applied more broadly to the spectrum of EMS systems. METHODS: A group of
      international EMD specialists, researchers and professional association
      representatives analyzed available scientific data and considered variations in
      EMS systems, particularly those in Europe and North America. RESULTS AND
      CONCLUSIONS: Several recommendations were established: (1) to avoid confusion,
      bystanders already providing CPR should continue those previously learned
      methods; (2) following a sudden collapse unlikely to be of respiratory etiology,
      CCOIs should be provided when the bystander is not CPR-trained, declining to
      perform mouth-to-mouth ventilation or unsure of actions to take; (3) following 4
      min of CCOIs, ventilations can be provided, but, for now, only at a compression
      ventilation ratio of 100:2 until EMS arrives; (4) until more data become
      available, dispatchers should follow existing compression-ventilation protocols
      for children and adult cases involving probable respiratory/trauma etiologies;
      (5) EMD CPR protocols should account for EMS system features and receive quality
      oversight and expert medical direction.

PMID- 15866403
TI  - Time course variations of haemodynamics, plasma volume and microvascular fluid
      exchange following surface cooling: an experimental approach to accidental
      hypothermia.
AB  - OBJECTIVE: To describe how surface cooling influences fluid distribution,
      vascular capacity and haemodynamic variables. METHODS: Seven anaesthetised pigs,
      following normothermic stabilization for 60 min, were cooled to 27.8+/-1.6
      degrees C. Fluid balance, haemodynamics, colloid osmotic pressures
      (plasma/interstitial fluid), haematocrit [s-albumin/protein] were recorded and
      plasma volume measured together with tissue perfusion during normothermia,
      cooling and stable hypothermia (coloured microspheres). Fluid shifts and changes
      in albumin and protein masses were calculated. At the end tissue water content
      was assessed. RESULTS: Haemodynamic variables changed with the start of cooling
      in parallel with a decreasing cardiac output. During hypothermia the haematocrit
      increased from 0.31+/-0.01 to 0.35+/-0.01 (P < 0.01). Plasma volume decreased
      from 1139.0+/-65.4 ml at start of cooling to 882.0+/-67.5 ml 3 h later (P <
      0.05). In parallel the plasma albumin and protein masses decreased from 37.8+/
      2.5 g and 54.6+/-4.0 g to 28.0+/-2.7 g (P < 0.05) and 41.2+/-4.1 g (P > 0.05),
      respectively. The main changes occurred 120-180 min after start of each
      experiment. In this period the fluid extravasation rate was elevated (P < 0.05)
      without influencing the colloid osmotic pressure of plasma/interstitial fluid.
      The increased fluid filtration was reflected by an increase in tissue water
      content. CONCLUSION: Our results are in favour of a shift of plasma from
      circulation to the interstitial space during surface cooling. This conclusion is
      based on the parallel losses of fluid and proteins from circulation with
      unchanged colloid osmotic pressures (plasma/interstitial fluid). Inflammation may
      be involved.

PMID- 15866404
TI  - Resuscitation failure due to Fraser syndrome in a newborn undiagnosed in the
      prenatal period.
AB  - Long segment laryngo-tracheal atresia is rare, and is usually incompatible with
      life in neonates. We report a case of an infant with Fraser syndrome that had not
      been diagnosed in the prenatal period who presented with impossible intubation
      due to severe long segment laryngeal atresia in the delivery room. Antenatal
      diagnostic features of Fraser syndrome and emergency airway management are
      discussed.

PMID- 15866405
TI  - An increase of BNP levels in massive pulmonary embolism and the reduction in
      response to the acute treatment.
AB  - Type B Natriuretic Peptide (BNP) is a neurohormone that is secreted from the
      cardiac ventricles in response to dilatation or an increase of pressure. Right
      ventricle dysfunction is seen in pulmonary embolism patients, but it may be hard
      to diagnose. Echocardiography is the most sensitive means of diagnosis for acute
      right ventricle dysfunction. However, echocardiography is also limited in some
      ways. BNP levels may increase with right ventricle dysfunction when the patients
      is in bed and decrease with treatment. We presented a case study in which
      diagnosed with mitral valve regurgitation, pulmonary embolism and pregnant for
      1.5 months. Initial BNP levels of 633 pg/ml decreased to 233, 65.2, 58.4 levels
      respectively which was parallel to improvements in the clinical state and right
      ventricle function detected in echocardiography. We used a rapid bedside test for
      determination of BNP.

PMID- 15866406
TI  - Airway management with the Laryngeal Tube Suction II in a patient with cervical
      spine injury.
AB  - Supraglottic airway devices may offer alternative strategies for securing the
      airway in patients with cervical spine injuries. A case of airway management with
      the LTS II, a modified version of the laryngeal tube suction, in a patient with a
      paramedian atlas fracture scheduled for decompression of a haematoma on the
      forehead is described. Device insertion was successful in the first attempt and a
      gastric tube was inserted without problems. Ventilation was uneventful, no
      complaints were stated after surgery.

PMID- 15866408
TI  - Intraoperative sonography of intra- and extramedullary tumors.
AB  - Intraoperative ultrasound (IOUS) was used in planning the operative resection of
      intradural spinal tumors, to define its diagnostic potential and limitations.
      Since 1997, 78 patients diagnosed with an ependymoma (n = 24), astrocytoma (n =
      7), hemangioblastoma (n = 7), neurinoma (n = 15), meningioma (n = 17) and filum
      terminale ependymoma (n = 8) were examined using intraoperative transdural
      sonography. Intramedullary tumors turned out to show a heterogeneous image with
      occasional cystic alterations and an indistinct demarcation to the myelon of
      comparable echogenicity. Intramedullary tumors are easily distinguishable from
      their extramedullary counterparts, which display a homogeneous signal intensity
      and sharp demarcation on IOUS. In conclusion, IOUS allows a reliable diagnosis of
      intraspinal tumors, allowing the distinction between intra- and extramedullary
      tumors through their respective signal characteristics. Using IOUS, the extension
      of the neurosurgical approach can be adopted to the true extent of the tumor;
      thus, avoiding further bone work while the dura is already opened and the
      frequently edematous spinal cord protrudes through the opening. Our experiences
      have shown that IOUS may reduce the procedure-related morbidity and should,
      therefore, be used as a standard intraoperative tool in these high-risk surgical
      entities. (E-mail: ).

PMID- 15866409
TI  - Liver steatosis classification using high-frequency ultrasound.
AB  - High-frequency B-mode images of 19 fresh human liver samples were obtained to
      evaluate their usefulness in determining the steatosis grade. The images were
      acquired by a mechanically controlled single-crystal probe at 25 MHz. Image
      features derived from gray-level concurrence and nonseparable wavelet transform
      were extracted to classify steatosis grade using a classifier known as the
      support vector machine. A subsequent histologic examination of each liver sample
      graded the steatosis from 0 to 3. The four grades were then combined into two,
      three and four classes. The classification results were correlated with
      histology. The best classification accuracies of the two, three and four classes
      were 90.5%, 85.8% and 82.6%, respectively, which were markedly better than those
      at 7 MHz. These results indicate that liver steatosis can be more accurately
      characterized using high-frequency B-mode ultrasound. Limitations and their
      potential solutions of applying high-frequency ultrasound to liver imaging are
      also discussed.

PMID- 15866410
TI  - In vivo elastographic investigation of ethanol-induced hepatic lesions.
AB  - Ethanol-induced hepatic lesions were investigated in swine for in vivo use as a
      strain imaging animal model. Lesions (n = 25) were induced by injecting ethanol
      (doses 0.33 to 2.0 mL) directly into the surgically exposed liver at depths of
      12, 15 or 25 mm. Lesions were imaged with a modified HDI 1000 scanner (Philips
      Medical Systems, Bothell, WA, USA). The elastograms (n = 91) characterized
      lesions as being areas harder than the surrounding soft hepatic tissue.
      Elastographic lesion sizes and the corresponding injected ethanol dose used to
      induce the lesions were shown to be statistically significant (r(2) = 0.22; p =
      0.029) using a linear regression analysis. Additionally, lesion depth was shown
      to be statistically insignificant (r(2) < 0.12; p > 0.10) when regressed against
      elastographic lesion size. An analysis of elastographic and gross pathology
      lesion sizes indicated no correlation (r(2) < 0.01; p = 0.973). Subsequently,
      lesion types were sorted by size and regression lines were computed from
      quasilinear regions of the corresponding run charts. Trend lines indicate a four
      to-three size relationship between the selected elastographic and pathology
      lesion sizes. Comparison of elastogram lesion sizes from two independent
      observers using a paired t-test resulted in no statistically significant
      difference (p = 0.14). In conclusion, ethanol-induced hepatic lesions in swine is
      a suitable animal model for evaluation of strain-based imaging systems, due to
      the ease of generation and repeatability.

PMID- 15866411
TI  - RF signals provide additional information on embolic events recorded during TCD
      monitoring.
AB  - Transcranial Doppler ultrasound (TCD) is commonly used to detect embolic signals
      in the cerebral circulation. However, current techniques to discriminate between
      signals from emboli and artifacts are subjective and ambiguous. The
      radiofrequency (RF) signal provides an extra dimension to the information
      available from conventional TCD systems that may help to interpret complex
      events. Artifacts generated by healthy volunteers and embolic signals recorded
      from a flow phantom were used to characterize the appearance of the two types of
      event. Characteristics of events, recorded during and immediately after carotid
      endarterectomy surgery, were compared with those from known sources. Additional
      information was provided by the RF signal on events recorded during TCD
      monitoring thus aiding classification. The RF signal may have a role as a "gold
      standard" for embolus detection.

PMID- 15866412
TI  - The ability of peripheral quantitative ultrasound to identify patients with low
      bone mineral density in the hip or spine.
AB  - This study aims to assess the sensitivity and specificity of two commercially
      available quantitative ultrasound (QUS) scanners (CUBA Clinical, Sunlight
      Omnisense), to differentiate patients with osteoporosis (OP) or osteopenia at the
      spine and hip confirmed by dual-energy x-ray absorptiometry (DXA) and to
      investigate the optimum cut-off values to maximize the effectiveness of the
      screening technique. Participants (n = 268) received DXA scans on their lumbar
      spine (L1-L4) and hip, with paired QUS scans on their distal radius, proximal
      phalanx, midshaft tibia and calcaneus. Scanners were evaluated by using receiver
      operating characteristics curves and their area under the curve (AUC) values.
      Measurement of the calcaneus by the CUBA Clinical showed a superior ability to
      predict DXA, with AUC values between 0.75 to 0.83 in comparison with AUC values
      of 0.60 to 0.70 for the Sunlight Omnisense. Cut-off values varied according to
      the technique used and the accuracy of the screening required. Assessment of the
      calcaneus was the best QUS technique for the prediction of low bone density at
      the axial skeleton as diagnosed by DXA.

PMID- 15866413
TI  - Comparison of three ultrasonic axial transmission methods for bone assessment.
AB  - This study compared three approaches to bone assessment using ultrasonic axial
      transmission. In 41 fresh human radii, velocity of the first arriving signal was
      measured with a commercial device (Sunlight Omnisense) operating at 1.25 MHz, a
      prototype based on 1-MHz bidirectional axial transmission and a low-frequency
      (200 kHz) prototype, also measuring the velocity of a slower wave. Cortical and
      trabecular bone mineral density, cortical thickness and cross-sectional area were
      determined by peripheral quantitative computed tomography. Significant but modest
      correlation between velocities reflects differences in the nature of the
      propagating waves and methodological differences. Of the higher frequency
      devices, bidirectional measurements provided stronger correlations with bone
      properties than did conventional measurements. High-frequency devices were less
      sensitive to cortical thickness than was the low-frequency device, because higher
      frequency waves interrogate thinner cortical layers. The results suggest that
      different axial transmission approaches reflect different bone properties.
      Therefore, a multifrequency technique might be useful in probing different bone
      properties.

PMID- 15866414
TI  - The effects of therapeutic ultrasound on heart rate variability: a placebo
      controlled trial.
AB  - The effect of therapeutic ultrasound (US) on nervous system is controversial and
      the effect on autonomic nervous system is not clear. Therefore, the present
      placebo-controlled trial was planned to investigate the effects of therapeutic US
      application on right-side stellate ganglion, by using analysis of heart rate
      variability (HRV). A total 12 healthy volunteers were included in the study. RR
      intervals were recorded for 5 min before and after the US application, in supine
      and sitting positions. All procedures were repeated in all participants with sham
      US one week later. The heart rate (HR) was obtained by time-domain analysis and
      low frequency (LF) power (%), high frequency (HF) power (%) and LF/HF ratio
      values were obtained by frequency-domain (power spectral density) analysis. After
      the US application, there was a decrease in the HR (p = 0.002) and the HF power
      (%) component (p = 0.015) in supine position and a decrease in HR (p = 0.002) and
      LF/HF ratio (p = 0.028) in sitting position. There was no significant difference
      after the sham US application. In conclusion, we observed that therapeutic US
      application on stellate ganglion causes alterations on HRV parameters.

PMID- 15866415
TI  - Adaptive brightness transfer functions in echocardiography.
AB  - Despite the clear advantages of echocardiography as a diagnostic tool, its images
      tend to be noisy and unclear. This paper presents an innovative algorithm, called
      ABTF (adaptive brightness transfer function), designed to optimally adjust the
      gray-levels used in echocardiography. The algorithm is aimed at aiding in visual
      tissue classification and texture-based visual tissue tracking in
      echocardiographic images. The ABTF method is based on fitting the cine-loop's
      gray-level histogram to a sum of three Gaussian functions, each of which relates
      to a different region within the image, the left ventricular cavity, the
      relatively dark regions within the cardiac muscle and the bright regions within
      the cardiac muscle. The procedure's feasibility has been supported by a test-set,
      including 23 echocardiographic cine-loops from 10 different patients. The
      resulting image quality appears to be superior to that of the original images,
      tending to show better contrast and a higher dynamic range of gray-levels within
      the cardiac muscle. According to two expert cardiologists, who have blindly
      ranked the image quality of each cine-loop on a scale from 1 to 10, where 10
      corresponds to the highest possible image quality, the mean score of the original
      cine-loops is 7.1 +/- 1.1, while the mean score of the cine-loops to which ABTF
      has been applied is 8.0 +/- 1.2.

PMID- 15866416
TI  - Effect of vessel curvature on Doppler derived velocity profiles and fluid flow.
AB  - Side-branches and curvatures in the arterial tree yield deviations from the axial
      oriented velocity. Velocity or volume flow estimates based on the assumption that
      flow is axially oriented are of limited value at these sites. This article
      evaluates information obtainable by using a multigate Doppler ultrasound (US)
      instrument used with curved phantoms, which resemble the human coronary arteries.
      The comparison of experimental velocity data with data provided by an accurate
      computational fluid dynamics (CFD) method shows differences in the range of 4 to
      11% for four curvatures with different radii. Multigate data are also used to
      estimate the volume flow in the curved segments at different experimental
      conditions. An error lower than 15% is obtained, to be compared with a 24% error
      obtained by assuming a parabolic velocity profile. In particular, it is shown
      that the residual error is not related to the small deviation of the velocity
      vectors from the axial direction due to the presence of secondary velocity
      components, which are found to be of magnitude less than 10% with respect to the
      axial velocity component.

PMID- 15866417
TI  - On the relationship between encapsulated ultrasound contrast agent and pressure.
AB  - Noninvasive measurement of pressure within the heart cavities and other internal
      organs (e.g., kidney, liver) has significant clinical value, but currently is not
      feasible. Noninvasive pressure estimation using encapsulated ultrasound (US)
      contrast agents (UCA) as sensors is a challenge because they supposedly respond
      to their ambient pressure, but they are more rigid and less sensitive to pressure
      than gas microbubbles. Here, Optison sensitivity was studied (f(resonance) =
      approximately 2 MHz) to varying pressures, when excited at 2 times and also at
      0.5 times f(resonance). Cyclic momentary increases in ambient pressure of 0 to 5,
      0 to 10, 0 to 15 or 0 to 20 kPa at 1.0 Hz, mimicking left ventricular (LV)
      pressure changes, caused amplitude decrease of echoes at 0.5, 1 and 2 times the
      transmitted frequency and decrease of attenuation. Changes at 0.5 times the
      transmitted frequency correlated best, but only after 70 to 150 s. The
      correlations (mean +/- SD) during 150 to 300 s were 0.706 +/- 0.072 for 0 to 10
      kPa, 0.844 +/- 0.042 for 0 to 15 kPa and 0.859 +/- 0.031 for 0 to 20 kPa.
      Attenuation presented less correlation. For 1.0 Hz, 10 to 15 kPa or 15 to 20 kPa
      pressures, mimicking systemic pressures, the attenuation decayed fast and even
      faster for slow (0.05 Hz) cyclic varying pressures, or elevated steady-state
      pressures (of 10 kPa and 20 kPa). Thus, cyclic pressure effects on UCA are
      demonstrated to be reversible, but elevated static pressures cause UCA
      destruction. This allows cyclic pressure variations to be detected, using the
      subharmonics of the transmitted frequency, down to 10 kPa.

PMID- 15866418
TI  - Augmentation of cardiac protein delivery using ultrasound targeted microbubble
      destruction.
AB  - Gas-filled microbubbles have become an important tool as ultrasonic contrast
      agents. We have previously shown that ultrasound-targeted microbubble destruction
      (UTMD) can direct plasmids to the heart. The aim of this study was to evaluate
      UTMD for protein delivery. Six different groups of rats received 1 microg of
      luciferase protein with varying protocols: (1) luciferase-loaded microbubbles and
      ultrasound; (2) luciferase only; (3) luciferase and ultrasound; (4) luciferase
      loaded microbubbles; (5) unloaded microbubbles incubated with luciferase and
      ultrasound; (6) unloaded microbubbles with ultrasound followed by luciferase.
      Relative luminescence units per mg protein per s were determined in hearts and
      control organs. The rats that received ultrasound and luciferase-loaded bubbles
      showed a six-fold higher cardiac luciferase uptake compared with control groups
      that did not include bubbles. None of the other groups significantly augmented
      cardiac luciferase activity. We conclude that ultrasound-targeted microbubble
      destruction can substantially and noninvasively augment organ-specific delivery
      of proteins.

PMID- 15866419
TI  - Insonation facilitates plasmid DNA transfection into the central nervous system
      and microbubbles enhance the effect.
AB  - Many of the diseases which affect the central nervous system are intractable to
      conventional therapies and therefore require alternative treatments such as gene
      therapy. Therapy requires safety, since the central nervous system is a critical
      organ. Choice of nonviral vectors such as naked plasmid DNA may have merit.
      However, transfection efficiencies of these vectors are low. We have investigated
      the use of 210.4 kHz ultrasound and found that 5.0 W/cm(2) of insonation for 5 s
      most effectively transfected a plasmid DNA into culture slices of mouse brain
      (147.68-fold increase compared with 0 W/cm(2) of insonation for 5 s). The effect
      was reinforced by combination with echo contrast agent, Levovist. One hundred
      fifty mg/mL of Levovist significantly increased gene transfection by ultrasound
      (5.23-fold when insonated at 5.0 W/cm(2) for 5 s). When DNA was intracranially
      injected, Levovist also enhanced gene transfection in newborn mice (4.49-fold
      increase when insonated at 5.0 W/cm(2) for 5 s). Since ultrasound successfully
      transfected naked plasmid DNA into the neural tissue and Levovist enhanced the
      effect, this approach may have a significant role in gene transfer to the central
      nervous system.

PMID- 15866420
TI  - Early gene response to low-intensity pulsed ultrasound in rat osteoblastic cells.
AB  - The aim of the current research was to quantify the changes in gene expression in
      rat bone marrow derived stromal cells (BMSC) to low intensity pulsed ultrasound
      (LIPUS) during early time points after the ultrasound application. LIPUS at 1.5
      MHz, 30 mW/cm(2) was applied to BMSC for a single 20 min treatment. Real-time PCR
      was carried out to quantify the expression of early response genes and bone
      differentiation marker genes 0.5, 1, 3, 6 and 12 h after the end of the LIPUS
      treatment. Compared with the controls, LIPUS treatment resulted in elevated
      transient expression of early response genes (c-jun, c-myc, COX-2, Egr-1, TSC-22)
      as well as the bone differentiation marker genes, osteonectin and osteopontin, at
      3 h. This induction of early response genes as well as extracellular matrix genes
      associated with cell proliferation and differentiation may represent the effect
      of LIPUS to cells of osteoblastic lineage.

PMID- 15866421
TI  - Modeling of the heat distribution in the intervertebral disk.
AB  - The heat transfer equation was used to model the heat distribution in an
      intervertebral disk during ultrasound (US) exposure. The influence of thermal and
      acoustic parameters was studied to get a quantitative understanding of the heat
      transfer in the system. Heating of collagen to 65 degrees C or above will lead to
      denaturation and is believed to stabilize and contract the outer part of the disk
      in a herniated disk. In our model, the US intensity was approximated by a
      Gaussian distribution and nonlinear propagation was excluded. The effect of self
      heating and cooling of the transducer was also studied. The simulations were
      performed using the finite element method. From this model, it can be concluded
      that it is possible to heat parts of the disk to treatment temperature using a
      focused 5-mm diameter US probe. The physical constraints on the piezocrystal set
      the limit of the size of the treatment volume.

PMID- 15866422
TI  - Functional role of Rab11 in GLUT4 trafficking in cardiomyocytes.
AB  - We have recently shown the co-localization of Rab11 and the glucose transporter
      GLUT4 in cardiac muscle and an insulin-stimulated increase of Rab11 in GLUT4
      containing vesicles in this tissue. We now assessed the effect of Rab11 wt and a
      dominant-negative mutant (N124I) on GLUT4 trafficking in the cardiomyoblast cell
      line H9c2 stably overexpressing the insulin receptor (H9c2-E2) and in human
      primary skeletal myotubes. These cells were used for transient cotransfection or
      adenoviral co-infection with GLUT4myc and Rab11 wt or N124I with subsequent
      determination of 2-deoxyglucose (2-DOG) uptake and GLUT4myc translocation.
      Concomitant overexpression of GLUT4myc and Rab11 wt in cardiomyocytes decreased
      the amount of GLUT4myc at the cell surface by about 50%, an effect not observed
      for Rab11 N124I. However, the dominant-negative mutant reduced the efficiency of
      insulin to promote glucose uptake and GLUT4 translocation in both cardiac and
      skeletal muscle cells to about one half. The level of Akt phosphorylation does
      not vary after cotransfection indicating that insulin signalling remained
      unaffected under these conditions. In conclusion, our data show that Rab11 (i)
      mediates endocytosis of GLUT4 and (ii) plays a pivotal role in insulin-regulated
      translocation of this transporter to the plasma membrane.

PMID- 15866423
TI  - N-linked glycosylation facilitates processing and cell surface expression of rat
      luteinizing hormone receptor.
AB  - The extracellular domain of the luteinizing hormone (LH) receptor has six
      potential N-linked glycosylation sites. Although previous studies have shown that
      mutation of the first three sites results in decreased ligand binding at the cell
      surface, the role of glycosylation in LH receptor processing is not understood.
      In the present study, we examined whether mutation of the first three sites has
      any affect on receptor synthesis, processing, and degradation of the mutant
      receptors. The data show that mutation of N77, N152, or N173 did not affect
      receptor synthesis, but did significantly reduce processing of the receptor
      precursor to the mature, cell surface form. Furthermore, defective processing was
      due to increased degradation of the precursor rather than increased turnover of
      cell surface receptors. Thus, lack of glycosylation decreases LH receptor
      processing and targets the receptors for degradation thereby leading to decreased
      cell surface expression. These results show that glycosylation of the LH receptor
      plays an important role in receptor processing and cell surface expression.

PMID- 15866425
TI  - Regulation of pancreatic somatostatin gene expression by insulin and glucagon.
AB  - Rainbow trout were used as a model system to study the effects of insulin and
      glucagon on the expression of preprosomatostatins (PPSS). We previously showed
      that the endocrine pancreas of trout contains three mRNAs that encode for
      distinct somatostatin-containing peptides: PPSS I, which contains somatostain-14
      (SS-14) at its C-terminus, and two separate PPSS IIs, PPSS II' and PPSS II'',
      each containing [Tyr7, Gly10]-SS-14 at their C-terminus. Rainbow trout injected
      (100 ng/g body weight) with insulin displayed elevated expression of PPSS II' and
      PPSS II'' mRNAs. Glucagon-injected (100 ng/g body weight) animals displayed
      elevated pancreatic expression of all PPSS mRNAs compared to saline-injected
      control animals. Insulin directly stimulated the expression of pancreatic PPSS
      II' and PPSS II'' mRNAs in vitro in a dose-dependent manner in the presence of
      4mM glucose. Glucagon, in the presence of 10mM glucose, directly stimulated the
      expression of all PPSS mRNAs in a dose-dependent manner in vitro. These results
      indicate that the pancreatic expression of PPSS mRNAs is differentially regulated
      by insulin and glucagon and that the regulatory pattern is dependent on glucose
      concentration.

PMID- 15866424
TI  - Selective activation of PPARgamma in breast, colon, and lung cancer cell lines.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a critical
      albeit poorly defined role in the development and progression of several cancer
      types including those of the breast, colon, and lung. A PPAR response element
      (PPRE) reporter assay was utilized to evaluate the selective transactivation of
      PPARgamma in 10 different cell lines including normal mammary epithelial, breast,
      lung, and colon cancer cells. Cells were treated with one of four compounds
      including rosglitizone (Ros), ciglitizone (Cig), 15-deoxy-Delta(12,14)
      prostaglandin J2 (PGJ2), or GW 9662 (GW). We observed differences in
      transactivation between cell lines from different tissue origin, across cell
      lines from a single tissue type, and selective modulation of PPARgamma within a
      single cell line by different ligands. Interestingly, GW, a PPARgamma antagonist
      in adipocytes, enhanced PPRE reporter activation in normal mammary epithelial
      cells while it had virtually no effect in any of the cancer cell lines tested.
      Within each cancer type, individual cell lines were found to respond differently
      to distinct PPARgamma ligands. For instance, Ros, Cig, and PGJ2 were all potent
      agonist of PPARgamma transactivation in lung adenocarcinoma cell lines while
      these same ligands had no effect in squamous cell or large cell carcinomas of the
      lung. Message levels of PPARgamma and retinoid X receptor alpha (RXRalpha) in the
      individual cell lines were quantitated by real time-polymerase chain reaction (RT
      PCR). The ratio of PPARgamma to RXRalpha was predictive of how cells responded to
      co-treatment of Ros and 9-cis-retinoic acid, an RXRalpha agonist, in two out of
      three cell lines tested. These data indicate that PPARgamma can be selectively
      modulated and suggests that it may be used as a therapeutic target for individual
      tumors.

PMID- 15866426
TI  - Estradiol and medroxyprogesterone acetate regulated genes in T47D breast cancer
      cells.
AB  - Many mammary tumors express estrogen receptors (ER) and progesterone receptors
      (PR), and there is increasing evidence that progestins influence gene expression
      of breast tumor cells. To analyse the impact of progestins on breast cancer
      cells, we compared (a) the expression of two cytokines, involved in tumor
      progression, and searched (b) for differentially regulated genes by a microarray,
      containing 2400 genes, on T47D breast cancer cells cultured for 6 days with
      17beta-estradiol (E2) or E2+medroxyprogesterone acetate (E2+MPA). Lower amounts
      of PDGF and TNFalpha were found in culture supernatants of E2+MPA treated T47D
      cells. MPA addition induced a 2.8-3.5-fold increase of the mRNA expression of (a)
      tristetraprolin, which is involved in the posttranscriptional regulation of
      cytokine biosynthesis, and (b) zinc-alpha2-glycoprotein and Na, K-ATPase alpha1
      subunit, which both resemble differentiation markers of breast epithelium. In
      contrast, the mRNA expression of lipocalin 2, which promotes
      matrixmetalloproteinase-9 activity, was decreased five-fold in E2+MPA treated
      cells. Our data show that the expression of genes from various functional gene
      families is regulated differentially by E2 and E2+MPA treatment in T47D cells.
      This suggests that exogenous progestins applied for therapy and endogenous
      changes of the progesterone levels during the menstrual cycle both influence
      breast cancer pathophysiology.

PMID- 15866427
TI  - Focal adhesion kinase is required for bombesin-induced prostate cancer cell
      motility.
AB  - Clinical evidence links neuroendocrine differentiation (NED) to prostate cancer
      progression. In the prostate carcinoma PC-3 cell model, the action of the gastrin
      releasing peptide (GRP) analog, bombesin (BN), on the activation of focal
      adhesion kinase (FAK) and invasiveness suggests that this kinase might favor
      metastasis. Given that components of the FAK signalling pathway are also up
      regulated in prostate cancer, the aim of the present investigation was to test if
      FAK function is required for BN-induced motility in PC-3 cells. In wound assays
      designed to investigate the fate of FAK in cells undergoing BN-induced motility,
      it was observed that BN treatment resulted in relocalization of FAK in focal
      contacts concomitantly with its tyrosine phosphorylation on residue 397 (FAK
      [pY(397)]) and with the formation of actin lamellipodia. Moreover, BN-induced
      cell motility was significantly reduced in the presence of FAK inhibitors (either
      anti-FAK [pY(397)] antibody or FRNK, the FAK-related non-kinase). Altogether,
      these observations point towards a critical role for FAK in the action of BN on
      PC-3 cell motility.

PMID- 15866428
TI  - Rasmussen's syndrome: progressive autoimmune multi-focal encephalopathy.
AB  - Rasmussen's encephalitis, originally thought to be a chronic form of viral
      encephalitis, is now thought to be an autoimmune disease of the brain and is more
      properly termed Rasmussen's syndrome. Starting in one area of one side of the
      brain, the disease appears to gradually and progressively involve that side of
      the brain causing progressive and intractable focal seizures, a hemiparesis, and
      expressive aphasia when the left hemisphere is involved. Immune therapy with
      steroids, immunoglobulins, or plasmaphoresis provide only temporary relief from
      seizures. Neither antibodies to Glu-R3 nor cortical biopsy are helpful in the
      diagnosis. Hemispherectomy of one form or another is the only curative therapy,
      and there is no evidence that one form of hemispherectomy is preferable to
      another. Immuno-ablative therapy may be a therapy of the future.

PMID- 15866429
TI  - Corticosteroids for the treatment of Landau-kleffner syndrome and continuous
      spike-wave discharge during sleep.
AB  - Landau-Kleffner syndrome and its variants such as continuous Spike-Wave Discharge
      during Sleep (CSWS) are progressive epileptic encephalopathies of childhood. The
      treatment of this unusual group of patients is controversial. We describe our
      experience in treating patients with Landau-Kleffner syndrome and CSWS with
      corticosteroids. The patients received Prednisone 1 mg/kg/day for 6 months, 1
      year, then yearly. Follow-up was for 1-10 years (mean 4 years). Ten patients, 3
      females, 7 males were studied. Age of onset ranged from 2 to 11 years (mean 7.5
      years). Eight patients manifested Landau-Kleffner syndrome, and two had CSWS.
      Most patients had seizures (8/10); however, two patients did not have clinical
      seizures. MRI was normal in all patients. SPECT scan was abnormal in four
      patients, normal in three, and not available in three. All but one patient
      manifested significant improvement in language, cognition, and behaviour, which
      continued after the corticosteroid trial. Side effects were few (4/10) and
      transient and consisted of weight gain (2), behavioral change (1), and
      hypertension (1). Corticosteroids are a safe and effective treatment for patients
      with Landau-Kleffner syndrome and CSWS. Most patients had improvement in
      language, cognition, and behaviour after treatment. Side effects are few and
      reversible, and benefits appear long lasting. Corticosteroids should be
      considered as a treatment option in children with Landau-Kleffner syndrome and
      CSWS.

PMID- 15866430
TI  - Neurologic complications associated with respiratory syncytial virus.
AB  - Encephalopathy has been demonstrated to be associated with respiratory syncytial
      virus bronchiolitis. In this study, the data on all patients less than 14 years
      of age hospitalized with respiratory syncytial virus bronchiolitis over the past
      4 years was reviewed. Patients who had concomitant diagnoses consistent with
      neurologic disease underwent detailed chart review. There were 964 patients (age
      0.1 to 13.6 years) with a diagnosis of respiratory syncytial virus bronchiolitis.
      Thirty-six of these patients had concurrent neurologic diagnoses. Twenty-four
      patients were excluded because of preexistent neurologic disorders, probable
      simple febrile seizures, or a history of epilepsy. Twelve respiratory syncytial
      virus-positive patients had definite neurologic complications without another
      recognized cause. Seven of these patients had seizures (predominantly generalized
      tonic-clonic and one with status epilepticus), three had generalized
      encephalopathy (marked hypotonia and decreased responsiveness) of whom two also
      developed esotropia. Two patients developed isolated esotropia. There was an
      incidence of neurologic complications of 1.2% (0.7% seizures) in a total of 964
      patients with respiratory syncytial virus bronchiolitis. This percentage does not
      include presumed simple febrile seizures or exacerbations of preexisting seizure
      disorder (further 1.3%). Neurologic complications occur with respiratory
      syncytial virus bronchiolitis, and physicians and other caregivers should be
      aware of this entity as well as the favorable prognosis.

PMID- 15866431
TI  - A comparison of spastic diplegic and tetraplegic cerebral palsy.
AB  - The aim of this study was to compare spastic diplegic and tetraplegic cerebral
      palsy. Thirty-eight children had spastic diplegic cerebral palsy and 48 spastic
      tetraplegic cerebral palsy. Risk factors of cerebral palsy, seizures, severity of
      cerebral palsy, electroencephalogram, and magnetic resonance imaging findings
      were analyzed. Gestational history, low birth weight, and perinatal pathologies
      were present in similar percentages in both groups. Lower values of the Apgar
      score were recorded more often in the tetraplegic cerebral palsy group than the
      diplegic group. The children with spastic diplegia were classified more
      frequently into levels I and II of the Gross Motor Function Classification
      System, but patients with spastic tetraplegia were classified more frequently
      into levels IV and V. Similarly, mental retardation was observed more frequently
      in the patients with spastic tetraplegia. In magnetic resonance imaging,
      periventricular leukomalacia was detected in a higher proportion of children with
      spastic diplegia than in patients with tetraplegia. Cerebral atrophy occurred
      more frequently in the tetraplegic group compared with diplegic patients. Twenty
      four (50.0%) children with spastic tetraplegia had epilepsy compared with six
      children with spastic diplegia. The incidence of intractable epilepsy was higher
      in the tetraplegic patients than in the children with spastic diplegia.

PMID- 15866432
TI  - Muscle coenzyme Q: a potential test for mitochondrial activity and redox status.
AB  - The aim of this study is to determine whether coenzyme Q (CoQ) muscle
      concentrations and redox state are associated with pathologic changes in muscle
      biopsy specimens. Skeletal muscle biopsies were collected (January 2002-February
      2004) and underwent pathologic evaluation. Quadriceps specimens (n = 47) were
      stratified accordingly: Group 1, controls without evidence of pathologic
      abnormalities; Group 2, type I myofiber predominance; Group 3, type II myofiber
      atrophy; Group 4, lower motor unit disease; and Group 5, muscular dystrophy.
      Ubiquinol-10, ubiquinone-10, total coenzyme Q10 (CoQ10), coenzyme Q9 (CoQ9),
      total CoQ (CoQ9+CoQ10) concentrations were analyzed in biopsy muscle by high
      performance liquid chromatography. Ubiquinone-10, total CoQ10, and total CoQ
      concentrations were significantly decreased in Group 5. Significant positive
      correlations (r congruent with 0.40) were found between muscle ubiquinone-10,
      total CoQ10, and total CoQ concentrations vs the percentage of myofibers having
      subsarcolemmal mitochondrial aggregates. CoQ redox ratio and the fraction
      CoQ9/total CoQ were negatively correlated with subsarcolemmal mitochondrial
      aggregates. A significant correlation (r = 0.328) also occurred between ubiquinol
      10 concentration and citrate synthase activity. This study suggests that total
      CoQ concentration provides a new method for estimating mitochondrial activity in
      biopsy muscle; and that the muscle CoQ test is feasible and potentially useful
      for diagnosing CoQ deficiency states.

PMID- 15866433
TI  - Diagnostic value of diffusion-weighted magnetic resonance imaging in pediatric
      cerebral diseases.
AB  - The purpose of this study was to detect the diagnostic value of diffusion
      weighted magnetic resonance imaging in different pediatric cerebral diseases
      involving the cerebral white and gray matter and to compare the diffusion
      properties with age-matched normal children. Conventional and diffusion-weighted
      magnetic resonance imaging were performed in 21 children with various neurologic
      disorders and 25 normal control subjects. Apparent diffusion coefficients were
      measured from the brain lesions and 12 normal-appearing white and gray matter
      areas in the study group. Twelve normal-appearing areas were also measured in the
      control group. Apparent diffusion coefficient values obtained from the normal
      subjects were similar to values described in the literature but were
      significantly different from the control subjects. Apparent diffusion coefficient
      values for the neurodegenerative disease group (n = 8), the anoxic encephalopathy
      group (n = 4), the subacute sclerosing panencephalitis group (n = 4), the acute
      disseminated encephalomyelitis group (n = 3), and the encephalitis group (n = 2)
      were respectively between 0.29-1.85 x 10(-5) cm2/s, 0.13-1.87 x 10(-5) cm2/s,
      0.96-1.57 x 10(-5) cm2/s, 0.49-0.73 x 10(-5) cm2/s, and 0.42-1.50 x 10(-5) cm2/s.
      Although this study is limited because of the size of the patient sample and
      disease heterogeneity, diffusion-weighted magnetic resonance imaging provides
      useful and complementary information regarding the degree of involvement in
      different pediatric neurologic disorders.

PMID- 15866434
TI  - Atypical presentations of leigh syndrome: a case series and review.
AB  - Patients with Leigh syndrome classically present in early childhood with
      developmental regression, ataxia, and hypotonia with subsequent respiratory and
      brainstem dysfunction. However, the clinical presentation can be highly variable.
      This report presents five cases of Leigh syndrome with atypical presentations.
      The first patient is a 17-month-old female who presented with progressive limb
      weakness diagnosed as Guillain-Barre syndrome. Postmortem examination
      demonstrated Leigh syndrome confined to the spinal cord. The case series then
      describes two sisters one of whom presented at 11 years of age with central
      respiratory failure and encephalopathy. Her 15-year-old sister presented with a
      progressive diplegia. The fourth patient presented with bronchiolitis and apnea
      at 3 months of age due to bilateral brainstem lesions. Her second cousin
      presented at 6 months of age with hypotonia, blindness, and tonic seizures. All
      patients had laboratory and radiologic findings consistent with Leigh syndrome.
      Evidence of spinal cord involvement was observed on magnetic resonance imaging in
      four of the five patients. Leigh syndrome can involve any level of the neuroaxis,
      resulting in a wide variety of presentations. Many atypical variants are
      observed, of which clinicians should be aware. Evidence of brainstem or spinal
      cord involvement should also be sought in patients with Leigh syndrome.

PMID- 15866435
TI  - Epilepsia partialis continua: acute disseminated encephalomyelitis or Rasmussen's
      encephalitis?
AB  - This report describes a 15-year-old male presenting with headaches and seizures
      after a viral illness progressing to intractable seizures of the right hand and
      face. This patient presented with diffuse white matter lesions on magnetic
      resonance imaging which disappeared with treatment. A relapse 6 months later
      involving the left temporal and insular regions produced epilepsia partialis
      continua involving the right face and hand. The relevant literature is reviewed
      with an emphasis on possible etiologies, including both acute disseminated
      encephalomyelitis and Rasmussen's encephalitis.

PMID- 15866436
TI  - CNS siderosis and dandy-walker variant after neonatal alloimmune
      thrombocytopenia.
AB  - This report presents a case of superficial siderosis of the central nervous
      system secondary to repeated intraventricular and subarachnoid bleeding of a
      newborn infant with neonatal alloimmune thrombocytopenia. In addition, this
      infant manifested Dandy-Walker variant. To date, the few known cases of
      superficial siderosis in neonates have not been associated with neonatal
      alloimmune thrombocytopenia or Dandy-Walker complex. We believe that repeated
      bleeding in the central nervous system from early fetal life, especially in the
      posterior fossa, may produce cerebellar atrophy as occurs in adults with
      superficial siderosis of the central nervous system.

PMID- 15866437
TI  - Ropinirole in a child with attention-deficit hyperactivity disorder and restless
      legs syndrome.
AB  - A 6-year-old male being treated with limited efficacy by methylphenidate
      immediate release for attention-deficit hyperactivity disorder also presented
      with sleep disruption due to potential restless legs/periodic limb movement
      syndrome. Treatment with the dopamine agonist ropinirole resulted in a
      significant improvement in both his attention-deficit hyperactivity disorder
      symptoms and sleep problems.

PMID- 15866438
TI  - Pediatric meningosarcoma: clinical evolution and genetic instability.
AB  - This report presents a female diagnosed with a frontoparietal interhemispheric
      meningosarcoma who, parallel to the clinical worsening, revealed an increase in
      the genetic instability (in bleomycin cultures) and the complexity of the
      karyotypes, with the acquisition of a clonal deletion of 17p13 (the locus for the
      TP53 tumor suppressor gene). The genetic findings of this patient suggest that
      the increased genetic instability could contribute to tumor progression as well
      as to treatment resistance, possibly in the background of the clonal deletion of
      TP53.

PMID- 15866439
TI  - Another patient with MECP2 mutation without classic Rett syndrome phenotype.
AB  - Rett syndrome and Angelman syndrome are two neurodevelopmental disorders
      characterized by partial overlapping features. Rett syndrome is frequently caused
      by a mutation in methyl-CpG-binding protein (MECP2) gene, localized on chromosome
      Xq28, whereas Angelman syndrome is frequently caused by different genetic
      anomalies at chromosome 15q11-q13 (deletions, uniparental disomy, imprinting
      center mutations, ubiquitin E3 ligase [UBE3A] gene mutations). Recently, some
      patients with a clinical diagnosis of Angelman syndrome were found to have a
      mutation in MECP2 gene. This report describes another patient with an Angelman
      like phenotype and with an MECP2 mutation.

PMID- 15866440
TI  - A family of Emery-Dreifuss muscular dystrophy with extreme difference in
      severity.
AB  - This report describes two patients, a father and son, with autosomal dominant
      Emery-Dreifuss muscular dystrophy. Although the father had the common phenotype,
      the son had a severe phenotype including early onset of weakness and fatal
      cardiomyopathy in childhood. Among the patients with severe phenotype of
      autosomal dominant Emery-Dreifuss muscular dystrophy, he is the first to have
      familial onset, and in the severe end of this disease spectrum.

PMID- 15866441
TI  - Costello syndrome showing moyamoya-like vasculopathy.
AB  - This report describes a patient with Costello syndrome associated with moyamoya
      like vasculopathy. His clinical findings were sparse, thin, and light-colored
      hair, bilateral ptosis, low-set ears, depressed nasal bridge, bulbous nose, short
      neck, loose pigmented skin with deep palmar and plantar creases, bilateral
      cryptorchidism, and delays in growth and development. Brain magnetic resonance
      imaging and cerebral angiography revealed moyamoya-like vasculopathy. A skin
      biopsy from the extensor surface of the right thigh revealed shortening and
      rupture of elastic fibers. Electron microscopy indicated reduced depositions of
      elastin. Formation of a stable elastic fiber system may be impaired in patients
      with Costello syndrome, and brain magnetic resonance imaging and magnetic
      resonance angiography would be recommended for these patients.

PMID- 15866442
TI  - Experimental study of the cross-sections of alpha-particle induced reactions on
      209Bi.
AB  - alpha-particle-induced nuclear reactions for generation of (211)At used in
      therapeutic nuclear medicine and possible contaminants were investigated with the
      stacked foil activation technique on natural bismuth targets up to E(alpha)=39
      MeV. Excitation functions are reported for the reactions
      (209)Bi(alpha,2n)(211)At, (209)Bi(alpha,3n)(210)At and (209)Bi(alpha,x)(210)Po.
      Results obtained from direct alpha-emission measurements and gamma-spectra from
      decay products are compared and correspond well with earlier literature values.
      Thick target yields have been deduced from the experimental cross-sections and
      optimised production pathways for minimal contamination are presented. A
      comparison with the results of the theoretical model code ALICE-IPPE is
      discussed.

PMID- 15866443
TI  - A high-resolution abrasive method for determining diffusion profiles of sorbing
      radionuclides in dense argillaceous rocks.
AB  - The diffusion of (134)Cs(+) and (22)Na(+) in Opalinus Clay (OPA) was studied by
      in-diffusion laboratory experiments. The diffusive tracer profiles in the rock
      were determined using a high-resolution abrasive peeling method. The radionuclide
      activities in the grinding swarf were measured directly via gamma-spectrometry.
      By choosing the appropriate abrasive paper, a resolution down to 15 microm can be
      achieved. This is important when analysing strongly sorbing radionuclides such as
      tri- and tetravalent actinides that show steep, shallow diffusion profiles. In
      this study, a resolution between 20 and 90 microm was obtained which was
      sufficient for a good spatial resolution of the diffusion profiles. Both the
      effective diffusion coefficients and the distribution coefficients of the
      radionuclides could be determined by applying a single reservoir with decreasing
      source concentration analysis for a semi-infinite case. In the case of (22)Na(+),
      effective diffusion coefficients of D(e)=2.0 x 10(-11)m(2)s(-1) and D(e)=1.5 x
      10(-11)m(2)s(-1) for Benken (Zurcher Weinland) OPA and Mont Terri OPA,
      respectively, were derived. The distribution coefficients were K(d)=3.1 x 10(-4)
      and 0.9 x 10(-4)m(3)kg(-1), respectively. For (134)Cs(+) the effective diffusion
      coefficients were higher, i.e. D(e)=3.1 x 10(-11)m(2)s(-1) for OPA from Benken
      and D(e)=3.0 x 10(-11)m(2)s(-1) for OPA from Mont Terri. The distribution
      coefficients determined were K(d)=0.16 m(3)kg(-1) for Benken and 0.23 m(3)kg(-1)
      for Mont Terri. Comparison of the data obtained for the weakly sorbing (22)Na(+)
      with those from earlier through-diffusion experiments showed that there is good
      agreement between the two methods. In the case of (134)Cs(+) such a comparison
      was not possible because through-diffusion data are not available. Because
      through-diffusion methods cannot be applied to strongly sorbing tracers in
      reasonable time periods, in-diffusion combined with high-resolution abrasive
      peeling offers an excellent alternative for measuring the diffusion properties of
      strongly sorbing tracers in dense argillaceous rocks.

PMID- 15866444
TI  - A process for the separation of 177Lu from neutron irradiated 176Yb targets.
AB  - A conceptual flowsheet has been developed for the separation of (177)Lu from a
      300 mg neutron irradiated (176)Yb enriched target. The key component of the
      process is an extraction chromatographic (EXC) resin containing 2-ethylhexyl 2
      ethylhexylphosphonic acid (HEH[EHP]) sorbed onto a 25-53 microm Amberchrom CG-71
      substrate. The process is divided into three sections: (1) front-end target
      removal system, (2) primary separation system and (3) secondary separation
      system. Each section involves the separation of Yb and Lu using the HEH[EHP]
      resin followed by concentration and acid adjustment of the Lu-rich eluate using
      an EXC material containing a diglycolamide extractant. The use of the
      diglycolamide EXC material is a significant feature of the flowsheet, allowing
      one to avoid lengthy evaporations and acidity adjustments between successive
      HEH[EHP] column runs while removing adventitious impurities from the (177)Lu. The
      overall recovery of (177)Lu is estimated at 73% with an overall decontamination
      factor from Yb of 10(6). The overall processing time can be as short as 4h.

PMID- 15866445
TI  - On the "artificial" nature of Tc and the "carrier-free" nature of 99mTc from
      99Mo/99mTc generators.
AB  - Two widespread misconceptions regarding Tc are dealt with. First, it is shown
      that although primordial Tc has decayed completely, Tc is still present in nature
      due to natural processes, in addition to substantial man-made quantities. Thus,
      Tc cannot be considered as a purely artificial element. Second, it is shown that
      (99m)Tc from (99)Mo/(99m)Tc generators is certainly not carrier-free (CF) and
      that, "no-carrier-added" (NCA) is a more appropriate designation. As a
      quantitative measure of the amount of long-lived (99g)Tc carrier present in
      (99m)Tc preparations from generators, the Isotope Dilution Factor (IDF) is used
      and calculated for some practical situations.

PMID- 15866446
TI  - Dosimetric parameters estimation using PENELOPE Monte-Carlo simulation code:
      Model 6711 a 125I brachytherapy seed.
AB  - The dosimetric parameters for characterization of a low-energy interstitial
      brachytherapy source (125)I are examined. In this work, the radial dose function,
      g(r), anisotropy function F(r,theta), and the absolute dose rate, Lambda, around
      (125)I seed model 6711 have been estimated by means of the PENELOPE Monte-Carlo
      (MC) simulation code. The results obtained are in good agreement with the
      corresponding values recommended by TG-43 that are based in experimental and MC
      published results.

PMID- 15866447
TI  - A new internal target system for production of (211)At on the cyclotron U-120M.
AB  - The alpha emitter (211)At is a radionuclide with good potential for use in the
      therapy of smaller tumours and metastases. However, limited availability of this
      radionuclide hinders development of this application and the research of astatine
      chemistry in general. In this general context we have designed and tested a new
      internal target system. A thin bismuth layer (3-5 microm) was evaporated onto a
      light target backing (7.5 g) and irradiated at 0.5-1.5 degrees angles with 29.5
      MeV alpha particles beam of intensity up to 30 microA. The backing was then
      released from the target holder and used directly for astatine separation via dry
      distillation. Astatine condensed on the Teflon capillary walls was then eluted
      into 150-250 microl of methanol. The saturation yield was found to be ca. 400
      MBq/microA, and the radionuclidic purity of (211)At acceptable for medical
      applications (activity ratio (210)At/(211)At<10(-3) at EOB). The overall
      separation yield was 65-75%.

PMID- 15866448
TI  - Simple automated preparation of O-[11C]methyl-l-tyrosine for routine clinical
      use.
AB  - The previously reported preparation of O-[(11)C]methyl-l-tyrosine ([(11)C]MT), a
      promising tumor imaging agent, has been now considerably simplified and
      automated. Main changes were the use of [(11)C]methyl iodide ([(11)C]MeI) in the
      reaction with l-tyrosine disodium and the use of solid phase extraction on
      commercially available cartridges instead of HPLC for the final purification. An
      injectable saline solution of [(11)C]MT was obtained within 30 min after EOB with
      radiochemical yield of ca. 60% (decay-corrected, based on [(11)C]MeI).
      Radiochemical purity was over 97%. The automated preparation was carried out
      using a miniature module employing manifold valves.

PMID- 15866449
TI  - A "cleanup procedure" involving periodate oxidation in the enzymatic synthesis of
      chemically pure alpha-32P and alpha-33P labelled deoxyribonucleotides.
AB  - Enzymatic synthesis of alpha-(32)P and alpha-(33)P labelled deoxyribonucleotides
      involves the transfer of radiolabelled phosphorus from either gamma-(32)P
      adenosine triphosphate (gamma-ATP) or gamma-(32)P guanosine triphosphate (gamma
      GTP). Subsequent removal of these ribonucleotides is essential for the
      preparation of chemically pure deoxyribonucleotides. Agarose-phenyl boronate
      columns, which bind specifically to cis-diol moieties, have been used for the
      removal of ribonucleotide contaminants. However, this involves column losses and
      additional radiation exposure. In the present work we describe a chemical method
      for the improvement of the chemical purity, based on the preferential oxidation
      of ribose sugars by periodate. The cis-diol moiety of ribose is specifically
      oxidised to the dialdehyde. The excess periodate ions were destroyed using
      ethylene glycol. The phosphate group was then cleaved by beta-elimination using
      alkali. The product was purified using anion exchange chromatography. The
      efficiency of the process was validated using tracer gamma-(32)P ATP and alpha
      (32)P dATP. Samples at various steps were analysed by TLC, autoradiography and
      HPLC. During the process ATP is oxidised whereas 2'-deoxyadenosine triphosphate
      (dATP) remains intact. The alpha-(32)P dATP synthesized by this process was
      assayed for its incorporation in lambda-DNA by the random priming method and was
      found to be effectively incorporated. The process developed is an efficient and
      convenient method for the preparation of chemically pure deoxyribonucleotides.

PMID- 15866450
TI  - Calibration of the NPL secondary standard radionuclide calibrator for the new 10R
      Schott, type 1+ vials.
AB  - For many years, P6 vials have been used for the distribution of a wide range of
      diagnostic and therapeutic radioactive solutions. The activity measurements were
      performed in this geometry and, in time, the UK calibration system for nuclear
      medicine was based on this container as a standard. However, one major supplier
      of radiopharmaceuticals has replaced the P6 vial with the 10R Type 1+ Schott
      vial. As the dimensions of the new vial are different from those of the P6 vial
      and the responses of radionuclide calibrators are known to be container
      dependent, the need for re-calibration became apparent. Preliminary measurements
      made on some typical radionuclide calibrators for (125)I solution indicated a
      difference in response of about 10% between the two vials. The master ionisation
      chamber of the NPL secondary standard radionuclide calibrator has been re
      calibrated and new calibration factors and volume correction factors for 10R
      Schott vials have been derived for the relevant medical radionuclides. The
      standard holder was also modified to accommodate the new larger vial. The
      complete list of factors and the method used to determine them is presented in
      this paper. The availability of these new factors will improve the quality of
      activity measurements in nuclear medicine, as calibration services can now be
      provided by NPL for the new container. These factors can also be employed for all
      commercial NPL secondary standard radionuclide calibrators (now known as the NPL
      CRC and previously as the 671 or ISOCAL IV).

PMID- 15866451
TI  - A statistical analysis of the initial biodistribution of 153Sm-EDTMP in a canine.
AB  - (153)Sm (t(1/2)=46 h) emits a 103 keV gamma photon and two medium-energy beta
      particles. Five mCi of Samarium-153 ethylenediaminetetramethylenephosphonic acid
      ((153)Sm-EDTMP) were administered to a clinically normal dog and whole body scans
      were obtained at 15min, 2h, and 24h post-injection (PI). Regions of interest
      (ROIs) were drawn representing abdomen, knee, rib, vertebral bodies, bladder,
      kidney, and liver, in each image. For each ROI, the mean intensity and standard
      deviation were computed, and a histogram was created. Clinically significant
      increased uptakes were found in liver and kidney.

PMID- 15866452
TI  - The dependence of the counting efficiency of Marinelli beakers for environmental
      samples on the density of the samples.
AB  - The effect of the density of the radioactive material packed in a Marinelli
      beaker on the counting efficiency was studied. It was found that for all
      densities (0.4-1.7 g/cm(3)) studied the counting efficiency (epsilon) fits the
      linear log-log dependence on the photon energy (E) above 200 keV, i.e. obeying
      the equation epsilon=alphaE(beta) (alpha, beta-parameters). It was found that for
      each photon energy the counting efficiency is linearly dependent on the density
      (rho) of the matrix. epsilon=a-brho (a, b-parameters). The parameters of the
      linear dependence are energy dependent (linear log-log dependence), leading to a
      final equation for the counting efficiency of Marinelli beaker involving both
      density of the matrix and the photon energy: epsilon=alpha(1) x Ebeta1 -
      alpha2Ebeta2rho.

PMID- 15866453
TI  - Experimental study and nuclear model calculations on the 192Os(p,n)192Ir
      reaction: Comparison of reactor and cyclotron production of the therapeutic
      radionuclide 192Ir.
AB  - In a search for an alternative route of production of the important therapeutic
      radionuclide (192)Ir (T(1/2)=78.83 d), the excitation function of the reaction
      (192)Os(p,n)(192)Ir was investigated from its threshold up to 20 MeV. Thin
      samples of enriched (192)Os were obtained by electrodeposition on Ni, and the
      conventional stacked-foil technique was used for cross section measurements. The
      experimental data were compared with the results of theoretical calculations
      using the codes EMPIRE-II and ALICE-IPPE. Good agreement was found with EMPIRE
      II, but slightly less with the ALICE-IPPE calculations. The theoretical thick
      target yield of (192)Ir over the energy range E(p)=16-->8 MeV amounts to only
      0.16MBq/muA.h. A comparison of the reactor and cyclotron production methods is
      given. In terms of yield and radionuclidic purity of (192)Ir the reactor method
      appears to be superior; the only advantage of the cyclotron method could be the
      higher specific activity of the product.

PMID- 15866454
TI  - Measurement of beta surface emission rate from an extended area 36Cl source using
      a multiwire proportional counter.
AB  - We have developed, as a national standard, a windowless multiwire proportional
      counting (MWPC) system for gross measurements of alpha- and beta-emitting
      radionuclides at an uncertainty level below 1%. Various detector characteristics
      have been studied and several working parameters of the system have been
      determined in order to achieve an optimized detection capability. The detector is
      commissioned through an international comparison of the beta emission rate from
      an extended area (36)Cl source. Correction for the dead time loss is made by the
      non-extendable dead time method. A linear extrapolation of pulse height spectrum
      is employed to correct for the loss in the detection efficiency due to
      discriminating against the events formed from a small number of original ion
      pairs. The surface emission rate was measured to be 1.84 x 10(3) counts/s with
      the relative combined standard uncertainty of 0.46%. The measured uncertainty
      indicates that the constructed MWPC is capable of serving as a national standard.

PMID- 15866455
TI  - Determination of disintegration rates and gamma-ray emission probabilities of
      65Zn and 241Am.
AB  - Radioactive solutions of (65)Zn and (241)Am were standardized within the frame of
      the CCRI (II)/BIPM key comparisons carried out recently in 2003. The activity
      concentrations (in Bqg(-1)) were determined using the 4pi(proportional counter)
      gamma coincidence counting method with efficiency extrapolation. Liquid
      scintillation methods were also used for (241)Am activity determination. The
      1115.5 keV of (65)Zn and the 26.35 and 59.54 keV of (241)Am gamma-ray emission
      probabilities were determined as 0.4971, 0.0206 and 0.3587, respectively, using a
      planar germanium detector. The associated relative uncertainties were 0.33%,
      1.56% and 0.47%, respectively.

PMID- 15866456
TI  - Uranium-series disequilibria as a means to study recent migration of uranium in a
      sandstone-hosted uranium deposit, NW China.
AB  - Uranium concentration and alpha specific activities of uranium decay series
      nuclides (234)U, (238)U, (230)Th, (232)Th and (226)Ra were measured for 16
      oxidized host sandstone samples, 36 oxic-anoxic (mineralized) sandstone samples
      and three unaltered primary sandstone samples collected from the Shihongtan
      deposit. The results show that most of the ores and host sandstones have close to
      secular equilibrium alpha activity ratios for (234)U/(238)U, (230)Th/(238)U,
      (230)Th/(234)U and (226)Ra/(230)Th, indicating that intensive groundwater
      rock/ore interaction and uranium migration have not taken place in the deposit
      during the last 1.0 Ma. However, some of the old uranium ore bodies have locally
      undergone leaching in the oxidizing environment during the past 300 ka to 1.0 Ma
      or to the present, and a number of new U ore bodies have grown in the oxic-anoxic
      transition (mineralized) subzone during the past 1.0 Ma. Locally, uranium
      leaching has taken place during the past 300 ka to 1.0 Ma, and perhaps is still
      going on now in some sandstones of the oxidizing subzone. However, uranium
      accumulation has locally occurred in some sandstones of the oxidizing environment
      during the past 1 ka to 1.0 Ma, which may be attributed to adsorption of U(VI) by
      clays contained in oxidized sandstones. A recent accumulation of uranium has
      locally taken place within the unaltered sandstones of the primary subzone close
      to the oxic-anoxic transition environment during the past 300 ka to 1.0 Ma.
      Results from the present study also indicate that uranium-series disequilibrium
      is an important tool to trace recent migration of uranium occurring in sandstone
      hosted U deposits during the past 1.0 Ma and to distinguish the oxidation
      reduction boundary.

PMID- 15866457
TI  - Reflection spectrometry analysis of irradiated GAFCHROMIC XR type R radiochromic
      films.
AB  - The absorption spectra of the GAFCHROMIC XR type R radiochromic film measured
      with reflectance spectroscopy have been investigated in order to analyze the
      dosimetry characteristics of the film. Like the XR type T film, this film
      features two peaks in its absorption spectrum, approximately at 676 and 618 nm,
      whose intensities increase with increasing absorbed dose. When the main
      absorption peak at 676 nm is used, the XR GAFCHROMIC type R film is approximately
      1.4 times more sensitive to radiation doses in the 0-5 Gy range than the XR type
      T film. The major difference of the films of this type from the original
      GAFCHROMIC film products is the opaque backing material, which permits only
      reflected, but not transmitted, light measurements as a means of analysis. A
      yellow dye is used as the opaque backing to enhance the visible color change for
      qualitative assessment of the delivered dose. The XR type R radiochromic film in
      combination with reflection spectroscopy can provide accurate assessment of
      doses.

PMID- 15866458
TI  - Preparation of a liquid nitrogen target for measurement of gamma-rays in the
      14N(n, gamma)15N reaction as an intensity standard in energy regions up to 11
      MeV.
AB  - We have developed a liquid nitrogen (N(2)) target that allows us to clearly
      measure gamma-rays below 2 MeV and to improve neutron beam availability. The
      intensity of the prompt 2223 keV gamma-ray from the (1)H(n, gamma) reaction in
      the present target could be reduced to about 160 in comparison with the one in
      the commercially available melamine (C(3)H(6)N(6)) target. The statistics of the
      full-energy-peak counts were improved by factors of 15-30 and about 4 in the
      energy regions below and above 2 MeV, respectively.

PMID- 15866459
TI  - Determination of hydrogen content in bulk samples using the neutron activation
      method.
AB  - The applicability of a new irradiation facility for bulk hydrogen analysis based
      on the activation method using thermal and epithermal neutrons has been tested
      for cylindrical samples of 8 cm diameter and 10 cm high. A definite correlation
      was found between the relative excess flux values, R and the total hydrogen
      contents, N(H) of the samples. Analytical expressions obtained for R vs. N(H)
      function indicate the possible use of this method even in the case of
      approximately kg weight and liter sample dimensions. The large sample has a
      special advantage if the determination of the hydrogen concentration, C(H) is in
      question.

PMID- 15866460
TI  - Measurement of K X-ray fluorescence cross-sections and yields for 5.96 keV
      photons.
AB  - The K(alpha), K(beta), and total K X-rays fluorescence cross-sections, as well as
      the average fluorescence yields for six elements with 16Z23 have been measured at
      5.96 keV. The areas of the K(alpha) and K(beta) spectral peaks, as well as the
      net peak areas, have been determined by a fitting process. Furthermore, the
      I(Kbeta)/I(Kalpha) intensity ratios for these elements have been investigated.
      The K X-rays emitted by samples have been counted by a Si(Li) detector.
      Experimental values of the K X-ray fluorescence cross-sections, fluorescence
      yields, and the I(Kbeta)/I(Kalpha) intensity ratios have been compared with
      theoretical values. In most cases, there is an agreement between the experimental
      and theoretical values within the standard uncertainties.

PMID- 15866462
TI  - Evaluation of the reticulocyte micronucleus assay in patients treated with
      radioiodine for thyroid cancer.
AB  - In the case of accidental radiation exposure, biological dosimetry has an
      important role. Previous studies have indicated that the flow cytometric
      micronucleus (MN) assay in human transferrin receptor positive reticulocytes (Tf
      Ret) in blood could be a sensitive biomarker for chromosome damage. In the
      present investigation, the utility and sensitivity of this method was studied in
      44 young patients from Belarus, who were treated with 131I for thyroid cancer.
      Red marrow (RM) is the critical organ in radioiodine therapy (RIT). In our
      patients, it was exposed to 100-700 mSv low-dose rate irradiation within 2-4
      days. About 3 days after 131I administration, the frequency of micronucleated-Tf
      Ret (f(MN-Tf-Ret)) increases within 1 day to a maximum and declines in the
      following 2-5 days to its value before treatment. A total dose of 100 mSv was
      easily detectable. The sensitivity of the assay after acute irradiation may be 50
      mSv. The method should be useful for monitoring individuals after a radiation
      accident, provided blood samples can be obtained within a few days after
      exposure. The time-course of f(MN-Tf-Ret) is interpreted using a model, which
      considers the exponential exposure of red marrow in RIT as well as the kinetics
      of erythroblast maturation and reticulocyte migration into the peripheral
      circulation. Similar modelling was done on published data of MN in immature mouse
      erythrocytes. Striking similarities in the kinetic and in the yield of MN
      induction were found between these two species. This lends support for the use of
      the mouse as a model for the MN-induction in humans.

PMID- 15866461
TI  - Effects of environmental benzene: micronucleus frequencies and haematological
      values in traffic police working in an urban area.
AB  - Among the toxic chemicals present in the ambient air of urban centres, benzene
      raises particular concern due to its haematoxicity and leukaemogenic hazards,
      probably related to clastogenic factors. However, little is known about the
      health risks associated with environmental--rather than industrial--exposure to
      benzene. We analysed micronucleus (MN) frequencies in peripheral lymphocytes by
      use of the cytokinesis-block technique, and haematological parameters among 49
      traffic police and 36 indoor workers (controls) in the city of Bologna. The
      analysis of urban air provided by a municipal air-quality monitoring station
      indicated that the levels of environmental benzene were often above the
      recommended threshold level (10 microg/m3) whereas other pollutants--nitrogen
      oxides, polycyclic aromatic hydrocarbon compounds, total suspended particulate
      matter, carbon monoxide, sulfur dioxide--did not exceed the maximum atmospheric
      concentration established for air-quality standards. Mean levels of individual
      airborne benzene exposure--as measured by personal devices worn during 4-h
      morning work-shifts--were six-fold higher in the traffic police than in controls
      (P=0.001). While no significant difference in haematological parameters was found
      between the two groups, MN frequency was significantly higher among the traffic
      police than in indoor workers (P=0.001). Among the study population, MN frequency
      was found to increase with age, but no influence was observed for gender or
      smoking. Although it cannot be excluded that the increase of MN frequency
      observed in traffic police could also depend, apart from benzene, on the complex
      mixture of pollutants encountered in urban air, our data indicate that elevated
      personal benzene exposure could represent a genetic risk. The analysis of
      biomarkers of genetic damage in subjects particularly exposed to environmental
      benzene deserves careful study.

PMID- 15866463
TI  - Induction of genotoxic and cytotoxic damage by aclarubicin, a dual topoisomerase
      inhibitor.
AB  - The anthracycline aclarubicin (ACLA) is an intercalative antibiotic and
      antineoplastic agent that efficiently binds to DNA, leading to a secondary
      inhibition of the catalytic activity of topoisomerase II (topo II) on DNA.
      Besides this activity, ACLA has been reported to exert a concomitant poisoning
      effect on topo I, in a fashion similar to that of the antitumor drug camptothecin
      and its derivatives. As a consequence of this dual (topo II catalytic
      inhibiting/topo I poisoning) activity of ACLA, the picture is somewhat confusing
      with regards to DNA damage and cytotoxicity. We studied the capacity of ACLA to
      induce catalytic inhibition of topo II as well as cytotoxic effects and DNA
      damage in cultured Chinese hamster V79 cells and their radiosensitive
      counterparts irs-2. The ultimate purpose was to find out whether differences
      could be observed between the two cell lines in their response to ACLA, as has
      been widely reported for radiosensitive cells treated with topo poisons. Our
      results seem to agree with the view that the radiosensitive irs-2 cells appear as
      hypersensitive ACLA as compared with radiation repair-proficient V79 cells. The
      recovery after ACLA treatment was also followed-up, and the irs-2 mutant was
      found to be less proficient than V79 to repair DNA strand breaks induced by ACLA.

PMID- 15866464
TI  - Effect of poly(ADP-ribosyl)ation inhibitors on the genotoxic effects of the boron
      neutron capture reaction.
AB  - The boron neutron capture (BNC) reaction results from the interaction of 10B with
      low-energy thermal neutrons and gives rise to highly damaging lithium and alpha
      particles. In this work the genotoxicity caused by the BNC reaction in V79
      Chinese hamster cells was evaluated in the presence of poly(ADP-ribosyl)ation
      inhibitors. Poly(ADP-ribose) polymerase-1 (PARP-1), the most important member of
      the PARP enzyme family, is considered to be a constitutive factor of the DNA
      damage surveillance network present in eukaryotic cells, acting through a DNA
      break sensor function. Inhibition of poly(ADP-ribosyl)ation was achieved with the
      classical compound 3-aminobenzamide (3-AB), and with two novel and very potent
      inhibitors, 5-aminoisoquinolinone (5-AIQ) and PJ-34. Dose-response increases in
      the frequencies of aberrant cells excluding gaps (%ACEG) and chromosomal
      aberrations excluding gaps per cell (CAEG/cell) were observed for increasing
      exposures to the BNC reaction. The presence of 3-AB did not increase the %ACEG or
      CAEG/cell, nor did it change the pattern of the induced chromosomal aberrations.
      Results with 5-AIQ and PJ-34 were in agreement with the results obtained with 3
      AB. We further studied the combined effect of a PARP inhibitor and a DNA
      dependent protein kinase (DNA-PK) inhibitors (3-AB and wortmannin, respectively)
      on the genotoxicity of the BNC reaction, by use of the cytokinesis-block
      micronucleus assay. DNA-PK is also activated by DNA breaks and binds DNA ends,
      playing a role of utmost importance in the repair of double-strand breaks. Our
      results show that the inhibition of poly(ADP-ribosyl)ation does not particularly
      modify the genotoxicity of the BNC reaction, and that PARP inhibition together
      with a concomitant inhibition of DNA-PK revealed barely the same sensitizing
      effect as DNA-PK inhibition per se.

PMID- 15866465
TI  - Increased DNA damage in patients with complete hydatidiform mole.
AB  - The pathologic mechanisms underlying the gestational trophoblastic diseases are
      largely unexplored, but are thought to involve oxidative damage to the maternal
      vasculature and also to the placenta. In this study we have assessed the plasma
      levels of total antioxidant response (TAR) and the levels of endogenous DNA
      damage--determined by the comet assay--in peripheral blood lymphocytes from 13
      women with complete hydatidiform mole (CHM) and compared these with those of 12
      healthy pregnant controls and 10 healthy non-pregnant controls. Significantly
      lower mean levels of plasma TAR were found in patients with CHM compared with
      healthy pregnant controls (1.08+/-0.29 versus 1.17+/-0.14 mmol Trolox Eq/L,
      p<0.05) and with healthy non-pregnant controls (1.08+/-0.29 versus 1.38+/-0.12
      mmol Trolox Eq/L, p<0.05). Significantly higher mean levels of endogenous DNA
      damage were observed in patients with CHM than in healthy pregnant controls
      (234.5+/-50.74 versus 125.7+/-45.4 AU, p<0.05) or in healthy non-pregnant
      controls (234.5+/-50.74 versus 104.0+/-49.6 AU, p<0.05). We observed an inverse
      correlation between the plasma TAR and the levels of endogenous DNA damage (r=
      0.64, p<0.01), in that the levels of oxidative damage to the DNA were found to
      parallel the decrease in the plasma TAR in the CHM group. These results reveal a
      relationship between the extracellular and intracellular (as reflected by damage
      to the DNA) levels of oxidation. Our observations suggest that there is a link
      between the increased levels of oxidative stress and the increase in endogenous
      DNA damage seen in patients with CHM, as compared with those seen in normal
      pregnancy. However, the nature of this link, and whether it is direct or
      indirect, remains to be explored.

PMID- 15866466
TI  - Bio-monitoring the genotoxicity of populations of Scots pine in the vicinity of a
      radioactive waste storage facility.
AB  - Results of a long-term (1997-2002) study of the Scots pine populations growing in
      the vicinity of the radioactive waste storage facility ('Radon' LWPE) are
      presented. Cytogenetic disturbances in reproductive (seeds) and vegetative
      (needles) tissues sampled from Scots pine populations were studied to examine
      whether Scots pine trees have experienced environmental stress in areas with
      relatively low levels of pollution. The data clearly indicate the presence of
      mutagenic contaminants in the environment of the pine trees. An increased number
      of mitotic abnormalities, especially multipolar mitoses was found in the pine
      tree populations submitted to man-made exposure, which suggests that the
      cytogenetic damage is mainly caused by chemical contamination. A higher
      radioresistance of the Scots pine seeds from the impacted populations was shown
      by use of acute gamma-irradiation. During the observation period 1997-2002, pine
      trees exposed to anthropogenic pollution showed a steady increase of cytogenetic
      alterations in the root meristem cells.

PMID- 15866467
TI  - Drosophila wing-spot test for genotoxic assessment of pollutants in water samples
      from urban and industrial origin.
AB  - The Cai River (Rio Grande do Sul, Brazil) is an important watercourse that
      receives large amounts of industrial and untreated municipal discharges in its
      lower course. We employed the SMART in Drosophila melanogaster to evaluate the
      genotoxicity of surface waters collected from Cai sites receiving direct sewage
      discharge: from Montenegro (Km 52) and from Sao Sebastiao do Cai (Km 78 and 80),
      and from two sites under the industrial influence (Km 13.6 and 18.6). The
      genotoxic analysis included three collections: March, June and September 1999,
      which were tested at crude sample and at 50 and 25% concentrations. Considering
      the industrial samples from Km 18.6 and 13.6, collected in March, June and
      September 1999, they were characterized as not having genetic toxicity. The urban
      samples collected in March--Km 52, 78 and 80--showed a significant increment in
      the frequencies of total spots. In Km 52 and 78 the genotoxic effect was
      associated to both mutational and recombinational events, although for Km 80 the
      increases observed were mainly related to the occurrence of homologous
      recombination. Moreover, the Km 80 crude sample from June and all the
      concentrations analyzed for Km 52 in September were also able to induce mitotic
      recombination. These effects were only observed in the ST cross, demonstrating
      the genotoxins present in the urban discharges act by direct interaction with the
      DNA of the somatic cells. The SMART in D. melanogaster was shown to be highly
      sensitive to detect genotoxic agents present in the aquatic environment, and must
      be better exploited for monitoring areas under anthropogenic discharges.

PMID- 15866468
TI  - Possible repair action of Vitamin C on DNA damage induced by methyl
      methanesulfonate, cyclophosphamide, FeSO4 and CuSO4 in mouse blood cells in vivo.
AB  - Interaction between Vitamin C (VitC) and transition metals can induce the
      formation of reactive oxygen species (ROS). VitC may also act as an ROS scavenger
      and as a metal chelant. To examine these possibilities, we tested in vivo the
      effect of two doses of VitC (1 and 30 mg/kg of mouse body weight) on the
      genotoxicity of known mutagens and transition metals. We used the alkaline
      version of the comet assay to assess DNA damage in peripheral white blood cells
      of mice. Animals were orally given either water (control), cyclophosphamide (CP),
      methyl methanesulfonate (MMS), cupric sulfate or ferrous sulfate. A single
      treatment with each VitC dose was administered after treatment with the mutagens
      or the metal sulfates. Both doses of VitC enhanced DNA damage caused by the metal
      sulfates. DNA damage caused by MMS was significantly reduced by the lower dose,
      but not by the higher dose of VitC. For CP, neither post-treatment dose of VitC
      affected the DNA damage level. These results indicate a modulatory role of
      Vitamin C in the genotoxicity/repair effect of these compounds. Single treatment
      with either dose of VitC showed genotoxic effects after 24 h but not after 48 h,
      indicating repair. Double treatment with VitC (at 0 and 24 h) induced a
      cumulative genotoxic response at 48 h, more intense for the higher dose. The
      results suggest that VitC can be either genotoxic or a repair stimulant, since
      the alkaline version of the comet assay does not differentiate "effective" strand
      breaks from those generated as an intermediate step in excision repair
      (incomplete excision repair sites). Further data is needed to shed light upon the
      beneficial/noxious effects of VitC.

PMID- 15866469
TI  - Comparison of genetic damage in Brazilian footwear-workers exposed to solvent
      based or water-based adhesive.
AB  - Research has shown that workers employed in footwear manufacture are at increased
      risk of some cancers, the strongest evidence being for nasal cancer and leukemia.
      Footwear-workers are routinely exposed to complex mixtures of solvents in
      degreasers, cleaners, primers, and adhesives used in the production process as
      toluene, n-hexane, acetone, and possibly dust particles, additives in shoe
      materials and degradation products of materials. The recognition of the potential
      health-hazards of solvent-based adhesives (SBAs) has lead to the development of
      adhesives with no organic solvents, the water-based adhesives (WBA). We
      investigated footwear-workers (all males) exposed to SBA (n=29) (for 3.98+/-4.13
      years), and WBA (n=16), which had spent the six months previous to the study
      employed in an experimental section which used only water-based adhesives,
      although they had previously worked in sections which used solvent-based
      adhesives (for 5.80+/-4.03 years); 25 healthy subjects were used as controls. The
      Comet assay and the micronucleus test were used as endpoints, while the
      traditional parameters for assessing exposure to toluene in organic mixtures by
      measuring the concentration of urinary hippuric acid were also assessed. Our
      results showed a significantly lower mean concentration of hippuric acid in the
      control group than found in the SBA (P<0.001) and WBA (P<0.05) groups. The Comet
      assay results showed that there was a significant increase in the mean damage
      index for the SBA (P<0.001) group in comparison to the WBA group and control
      (P<0.05). For the micronucleus test in binucleated lymphocytes and exfoliated
      buccal cell, the three groups were not statistically different. Our study
      demonstrated that water-based adhesives are clearly a better option for
      safeguarding the health of footwear-workers, even with possibility of isocyanate
      presence, while the positive results observed in SBA group might be explained by
      chloroprene presence in the adhesive.

PMID- 15866470
TI  - Prenatal and perinatal fenarimol-induced genotoxicity in leukocytes of in vivo
      treated rats.
AB  - The identification of environmental compounds that have adverse effects on
      reproductive health and animal development is particularly challenging.
      Fenarimol, a systemic fungicide, is considered non or weakly genotoxic. However,
      its available toxicological data are controversial and incomplete. This study was
      conducted in rat in vivo to determine whether this compound (150 and 300 mg/kg)
      had adverse effects on DNA integrity in dams and pups after maternal subcutaneous
      exposure. The animals were exposed during early gestation (1-6 days), late
      gestation (last 6 days), or first 6 days of lactation. Findings on fenarimol
      genotoxicity showed an adverse effect when detected by the Comet assay, both in
      dams and pup, and state that animal sensitivity to fenarimol is higher during
      postnatal period. Since the DNA damage increases during the time of exposure (2 h
      to 6 days after the birth), our data on pups suggest that fenarimol can mainly
      act on cell DNA through direct exposure of litter via milk.

PMID- 15866471
TI  - Update on paramyosin in parasitic worms.
AB  - Paramyosin was first identified as a structural component of invertebrate muscle.
      Analysis of crude, native, adult schistosome worm preparations identified a
      highly immunogenic protein which was later identified as paramyosin. Early
      vaccination/challenge studies with native paramyosin produced encouraging levels
      of protective efficacy against schistosomes, which led to the question as to how
      a sub-tegumental (muscular) protein could provide a target for vaccine-mediated
      immunological attack. Immunolocalisation studies of schistosomes confirmed the
      presence of paramyosin within the post-acetabular glands of cercariae and on the
      tegumental surface of lung schistosomula. Here we present an update on the more
      recent research on paramyosin in parasitic worms that has focused primarily in
      two directions: (i) further testing of the vaccine potency of paramyosin against
      schistosomes and other parasitic worms; and (ii) characterisation of the protein
      at the molecular and biochemical levels.

PMID- 15866472
TI  - The involvement of neutrophils in the resistance to Leishmania major infection in
      susceptible but not in resistant mice.
AB  - To understand the immunomodulatory roles of neutrophils in Leishmania major
      infection, we examined the expression of cytokine and chemokine mRNAs from
      neutrophils of the infected resistant C3H/HeJ and susceptible BALB/c mice. We
      also examined the effects of neutrophil depletion on the expression of cytokine
      by peritoneal macrophages and draining lymph node cells and on the footpad
      lesions and parasite burdens in these mice. Neutrophils from resistant C3H/HeJ
      but not from susceptible BALB/c mice expressed mRNAs for IL-12p40, IFN-gamma,TNF
      alpha and monokine induced by IFN-gamma(MIG). Neutrophil depletion of the
      resistant mice reduced the expression of IFN-gammaandTNF-alpha in peritoneal
      macrophages but did not affect the expression of IL-12p40 and IFN-gamma in
      draining lymph node cells and the growth of footpad lesions. On the other hand,
      neutrophil depletion of susceptible BALB/c mice did not affect the expression of
      TNF-alpha and monocyte-derived chemokine (MDC) in peritoneal macrophages but
      induced the early stage expression of IL-4 in draining lymph node cells and
      exacerbated the footpad lesions and increased the parasite burden. The
      exacerbation of footpad lesions induced by neutrophil depletion was abolished by
      rIL-12 treatment. Our results suggest that even in susceptible BALB/c but not in
      C3H/HeJ mice there is a certain resistance requiring neutrophils at the early
      stage of infection.

PMID- 15866473
TI  - Development of a modified MTT assay for screening antimonial resistant field
      isolates of Indian visceral leishmaniasis.
AB  - The semi-automated MTT colorimetric assay has previously been applied on
      Leishmania promastigotes based on the ability of viable parasites to reduce the
      tetrazolium salt to an insoluble formazan product. As promastigotes are non
      adherent, application of the MTT assay in its original form has a major drawback
      of a high and variable background absorbance due to incomplete removal of phenol
      red, a component of most media. We have accordingly optimised a modified MTT
      assay wherein the absorbance linearity was maintained for cells ranging from
      1x10(4) to 1x10(7) being 0.04+/-0.003-2.38+/-0.04. In contrast, the original MTT
      assay had a narrower linearity range of 1x10(6)-1x10(7) cells, absorbances being
      0.05+/-0.005-1.54+/-0.005. The modified MTT assay was effectively applied to
      study growth kinetics and identification of antimonial resistant field isolates.
      Considering the growing problem of antimonial unresponsiveness in the Indian
      subcontinent, this modified MTT assay is a useful tool for Leishmania research.

PMID- 15866474
TI  - Identification of an astacin-like metallo-proteinase transcript from the
      infective larvae of Strongyloides stercoralis.
AB  - Strongyloides stercoralis, an important nematode pathogen of humans, is
      transmitted by contact with soil contaminated with the microscopic larvae of the
      parasite. We determined the cDNA sequence and deduced amino acid structure of a
      metallo-proteinase that is abundantly transcribed expressed by infective stage
      larvae of S. stercoralis. This deduced structure of the enzyme revealed a multi
      domain protein that included an NH2-terminal peptidase. This peptidase consisted
      of a signal peptide, a pro-enzyme region, and a mature peptidase domain that
      included the metal ion co-ordinating motifs, HETSHALGVIH and SIMHY ("Met-turn"),
      characteristic of the catalytic active site of members of the metzincin
      superfamily of zinc metallo-endopeptidases. It was phylogenetically and
      structurally similar to astacin from the digestive gland of the crayfish Astacus
      astacus, to the HCH-1 peptidase of Caenorhabditis elegans required for hatching
      and migration of a post-embryonic neuroblast, and to the morphogenetically
      important peptidases, bone morphogenetic protein-1 (BMP-1) and Drosophila
      tolloid. In addition, the Strongyloides enzyme, designated strongylastacin,
      includes a central epidermal growth factor (EGF) domain followed by a carboxyl
      CUB (complement sub component C1r/C1s/embryonic sea urchin protein Uegf/bone
      morphogenetic protein) domain. Inspection of the dbEST database revealed the
      presence of at least 9 transcript clusters that are related to greater or lesser
      extent to strongylastacin; based on these expressed sequence tags,
      strongylastacin was expressed only in the infective third stage larvae, whereas
      other transcript clusters were expressed both in filariform and rhabditiform
      stages or only in the rhabditiform stage. Based on the deduced sequence,
      structure, and expression profile, strongylastacin is the probable candidate for
      the zinc-dependent metalloprotease, Ss40, known to be deployed by larvae of S.
      stercoralis to penetrate human skin to initiate infection.

PMID- 15866475
TI  - Medical treatment of pulmonary hydatid disease: for which child?
AB  - There have been many encouraging studies on medical treatment of pulmonary
      hydatid disease due to Echinococcus granulosus infection. Our aims were to
      demonstrate the safety and efficacy of medical treatment in pulmonary hydatid
      disease and to describe a pediatric population who would benefit from medical
      treatment, especially in respect to the diameter of the hydatid cyst. All
      patients were treated with mebendazole or albendazole. Treatment outcome was
      defined as cure, improvement or failure. Among 82 patients, 34.1% were cured,
      34.1% improved and 31.8% failed. When 102 cysts were individually evaluated,
      36.31% were cured, 32.4% improved and 31.3% failed. The cure and the failure
      rates were statistically insignificant in cysts treated with mebendazole and
      albendazole; however statistically significantly more cysts were improved with
      albendazole. The results were statistically insignificant between continuous and
      cyclic albendazole treatment. The mean size of successfully treated cysts was
      5.3+/-3.4 cm, but "failed" for cyst with a mean size of 7.3+/-4.3 cm. There was a
      positive, weak and statistically significant correlation between the cyst size
      and treatment results. The major complication was infection. We suggest that
      selected pediatric patients with uncomplicated pulmonary hydatid cysts sized less
      than 5 cm should have a trial of medical treatment with a very close follow up.

PMID- 15866476
TI  - Function of CD8+ T lymphocytes in a self-curing mouse model of visceral
      leishmaniasis.
AB  - CD8+ T lymphocytes play an important role in the control of visceral
      leishmaniasis in non self-cure mice (e.g. BALB/c). In the present study, the mode
      of action of CD8+ T cells and their in vivo contribution to immunity was
      addressed in self-curing C57BL/6 mice. During the course of the experimental
      infection, CD8+ T cells specific for Leishmania infantum (L. infantum) developed
      and apoptotic cell death subsequently followed. They exhibited perforin-dependent
      cytotoxicity and a T(C)1 profile characterized by secretion of IFN-gamma and CC
      chemokines. Despite evidence for activation of CD8+ T lymphocytes, both
      intravenous and intradermal infection of beta2-microglobulin deficient C57BL/6
      mice with L. infantum showed that these knockout animals had similar parasite
      loads to their wild-type counterpart. Lymphocytes from the beta2-microglobulin
      deficient mice produced high levels of IFN-gamma, reflecting a T(H)1 response to
      the parasite, which was apparently sufficient for the immunologic control of the
      pathogen. Thus, despite their functional activation, CD8+ T lymphocytes do not
      appear to play a primary role in parasite restraint in the self-curing mouse
      model of visceral leishmaniasis, as shown using beta2-microglobulin deficient
      mice which do not produce functional CD8+ T lymphocytes.

PMID- 15866477
TI  - Strongyloides ratti: chemokinesis of glycolytic enzyme- and lectin-treated third
      stage infective larvae in vitro.
AB  - The infective third-stage larvae (L3s) of Strongyloides ratti, a parasitic
      nematode in rodents, showed two types of chemokinesis on a gradient of sodium
      chloride (NaCl) in an in vitro agarose tracking assay. The types were a
      consistent directional avoidance behavior under unfavorable environmental
      conditions and a reduced avoidance behavior under favorable conditions. We
      examined the effects of treatments with glycolytic enzymes and lectins by
      analyzing the avoidance behavior. L-Fucose dehydrogenase, hyaluronidase, beta
      glucosidase, alpha-mannosidase, beta-galactosidase, concanavalin A, wheat germ
      agglutinin and soybean agglutinin exhibited inhibitory or enhancive effects on
      chemokinesis. We also confirmed the sites of the amphids of L3s aside from the
      mouth at the anterior end by scanning electron microscopy, and that concanavalin
      A-binding sites existed in the vicinity of the amphids using lectin
      histochemistry. The carbohydrate moieties in the amphids of S. ratti L3s may play
      an important role as chemosensors in perceiving environmental cues.

PMID- 15866478
TI  - Increases in NMR-visible lipid and glycerophosphocholine during phenylbutyrate
      induced apoptosis in human prostate cancer cells.
AB  - DU145 human prostatic carcinoma cells were treated with the differentiating
      agents phenylacetate (PA) and phenylbutyrate (PB) and examined in perfused
      cultures by diffusion-weighted 1H and 31P nuclear magnetic resonance spectroscopy
      (NMR). PA and PB (10 mM) induced significant (>3-fold) time-dependent increases
      in the level of NMR-visible lipids and total choline in 1H spectra, and
      glycerophosphocholine levels in the 31P spectra, with the increases being greater
      for PB. These effects were accompanied by significant increases in cytoplasmic
      lipid droplets and intracellular lipid volume fraction as observed by
      morphometric analysis of Oil Red O-stained cells. PB treatment caused cell cycle
      arrest in the G1 phase and induction of apoptosis. In contrast, PA-treated DU145
      cells showed an accumulation of cells in G2/M and no evidence of apoptosis. These
      results demonstrate that significant differences exist in the mechanism of PA and
      PB activity, although both compounds cause similar, but graded alterations in
      lipid metabolism. The simultaneous accumulation of mobile lipid and
      glycerophosphocholine suggests that PB and PA induce phospholipid catabolism via
      a phospholipase-mediated pathway. The mobile lipid accumulation following the
      induction of either apoptosis and cytostasis by related differentiating agents
      indicate that the presence of NMR-visible lipids may not be a specific event
      causally resulting from the induction of apoptosis.

PMID- 15866479
TI  - Environmental and dietary influences on highly unsaturated fatty acid
      biosynthesis and expression of fatty acyl desaturase and elongase genes in liver
      of Atlantic salmon (Salmo salar).
AB  - Highly unsaturated fatty acid (HUFA) synthesis in Atlantic salmon (Salmo salar)
      was known to be influenced by both nutritional and environmental factors. Here we
      aimed to test the hypothesis that both these effectors involved similar molecular
      mechanisms. Thus, HUFA biosynthetic activity and the expression of fatty acyl
      desaturase and elongase genes were determined at various points during an entire
      2 year production cycle in salmon fed diets containing either 100% fish oil or
      diets in which a high proportion (75% and 100%) of fish oil was replaced by C18
      polyunsaturated fatty acid-rich vegetable oil. The results showed that HUFA
      biosynthesis in Atlantic salmon varied during the growth cycle with peak activity
      around seawater transfer and subsequent low activities in seawater. Consistent
      with this, the gene expression of Delta6 desaturase, the rate-limiting step in
      the HUFA biosynthetic pathway, was highest around the point of seawater transfer
      and lowest during the seawater phase. In addition, the expression of both Delta6
      and Delta5 desaturase genes was generally higher in fish fed the vegetable oil
      substituted diets compared to fish fed fish oil, particularly in the seawater
      phase. Again, generally consistent with this, the activity of the HUFA
      biosynthetic pathway was invariably higher in fish fed diets in which fish oil
      was substituted by vegetable oil compared to fish fed only fish oil. In
      conclusion, these studies showed that both nutritional and environmental
      modulation of HUFA biosynthesis in Atlantic salmon involved the regulation of
      fatty acid desaturase gene expression.

PMID- 15866480
TI  - Role of MEK-ERK pathway in sphingosylphosphorylcholine-induced cell death in
      human adipose tissue-derived mesenchymal stem cells.
AB  - Sphingosylphosphorylcholine (SPC) is a bioactive lipid molecule involved in a
      variety of cellular responses. In the present study, we demonstrated that
      treatment of human adipose tissue-derived mesenchymal stem cells (hATSCs) with D
      erythro-SPC resulted in apoptosis-like cell death, as demonstrated by decreased
      cell viability, DNA strand breaks, the increase of sub-G1 fraction, cytochrome c
      release into cytosol, and activation of caspase-3. In contrast, the exposure of
      hATSCs to L-threo-SPC did not induce the cell death, suggesting that the SPC
      induced cell death was selective for the D-erythro-stereoisomer of SPC. The D
      erythro-SPC-induced cell death was prevented by DEVD-CHO, a caspase-3 specific
      inhibitor, and Z-VAD-FMK, a general caspase inhibitor, suggesting that the SPC
      induced cell death of hATSCs occurs through the cytochrome c- and caspase-3
      dependent pathways. In addition, D-erythro-SPC treatment stimulated the
      activation of mitogen-activated protein kinases, such as ERK and c-Jun NH2
      terminal protein kinase (JNK), and the D-erythro-SPC-induced cell death was
      completely prevented by pretreatment with the MEK inhibitor, U0126, but not by
      pretreatment with the JNK inhibitor, SP600125, and the p38 MAPK inhibitor,
      SB202190, suggesting a specific involvement of ERK in the D-erythro-SPC-induced
      cell death. Pretreatment with U0126 attenuated the D-erythro-SPC-induced release
      of cytochrome c. From these results, we suggest that ERK is involved in the SPC
      induced cell death of hATSC through stimulation of the cytochrome c/caspase-3
      dependent pathway.

PMID- 15866481
TI  - Isolation of very low density lipoprotein phospholipids enriched in ethanolamine
      phospholipids from rats injected with Triton WR 1339.
AB  - Phospholipids carried by very low density lipoprotein (VLDL) are hydrolysed in
      circulation by lipoprotein and hepatic lipases and lecithin-cholesterol
      acyltransferase. We have previously demonstrated [J.J. Agren, A. Ravandi, A.
      Kuksis, G. Steiner, Structural and compositional changes in very low density
      lipoprotein triacylglycerols during basal lipolysis, Eur. J. Biochem. 269 (2002)
      6223-6232] that the infusion of Triton WR 1339 (TWR), which inhibits these
      lipases, leads in 2 h to five-fold increase in VLDL triacylglycerol concentration
      along with major differences in the composition of their molecular species. The
      present study demonstrates that the accumulation of triacylglycerols is
      accompanied by major changes in the content of the VLDL phospholipids, of which
      the most significant is the enrichment of phosphatidylethanolamine (PtdEtn). This
      finding coincides with the enrichment in PtdEtn demonstrated in the VLDL of a
      hepatocytic Golgi fraction but it had not been demonstrated that the Golgi VLDL,
      along with its unusual phospholipid composition, can be directly transferred to
      plasma. Aside from providing an easy access to nascent plasma VLDL, the TWR
      infusion demonstrates that lipoprotein and hepatic lipases are also responsible
      for the degradation of plasma VLDL PtdEtn, as independently demonstrated for
      plasma phosphatidylcholine. Our results indicate also, with the exception of
      lysophosphatidylcholine, that preferential basal hydrolysis no dot lead to major
      differences in molecular species composition between circulating and newly
      secreted VLDL phospholipids. The comparison of the molecular species composition
      of VLDL and liver phospholipids suggests a selective secretion of PtdEtn and
      sphingomyelin molecular species during VLDL secretion.

PMID- 15866482
TI  - Endocytosis is not required for the selective lipid uptake mediated by murine SR
      BI.
AB  - The scavenger receptor class B, type I (SR-BI) mediates the cellular selective
      uptake of cholesteryl esters and other lipids from high-density lipoproteins
      (HDL) and low-density lipoproteins (LDL). This process, unlike classical receptor
      mediated endocytosis, does not result in lipoprotein degradation. Instead, the
      lipid depleted particles are released into the medium. Here we show that
      selective lipid uptake mediated by murine SR-BI can be uncoupled from the
      endocytosis of HDL or LDL particles. We found that blocking selective lipid
      uptake by incubating cells with the small chemical inhibitors BLT-1 or BLT-4 did
      not affect endocytosis of HDL. Similarly, blocking endocytosis by hyperosmotic
      sucrose or K+ depletion did not prevent selective lipid uptake from HDL or LDL.
      These findings suggest that mSR-BI-mediated selective uptake occurs at the cell
      surface upon the association of lipoproteins with mSR-BI and does not require
      endocytosis of HDL or LDL particles.

PMID- 15866483
TI  - Agonist-induced activation releases peroxisome proliferator-activated receptor
      beta/delta from its inhibition by palmitate-induced nuclear factor-kappaB in
      skeletal muscle cells.
AB  - The mechanisms by which elevated levels of free fatty acids cause insulin
      resistance are not well understood, but there is a strong correlation between
      insulin resistance and intramyocellular lipid accumulation in skeletal muscle. In
      addition, accumulating evidence suggests a link between inflammation and type 2
      diabetes. The aim of this work was to study whether the exposure of skeletal
      muscle cells to palmitate affected peroxisome proliferator-activated receptor
      (PPAR) beta/delta activity. Here, we report that exposure of C2C12 skeletal
      muscle cells to 0.75 mM palmitate reduced (74%, P<0.01) the mRNA levels of the
      PPARbeta/delta-target gene pyruvatedehydrogenase kinase 4 (PDK-4), which is
      involved in fatty acid utilization. This reduction was not observed in the
      presence of the PPARbeta/delta agonist L-165041. This drug prevented palmitate
      induced nuclear factor (NF)-kappaB activation. Increased NF-kappaB activity after
      palmitate exposure was associated with enhanced protein-protein interaction
      between PPARbeta/delta and p65. Interestingly, treatment with the PPARbeta/delta
      agonist L-165041 completely abolished this interaction. These results indicate
      that palmitate may reduce fatty acid utilization in skeletal muscle cells by
      reducing PPARbeta/delta signaling through increased NF-kappaB activity.

PMID- 15866484
TI  - Acidic residues emulate a phosphorylation switch to enhance the activity of rat
      hepatic neutral cytosolic cholesterol esterase.
AB  - Site-directed mutagenesis of rat hepatic neutral cytosolic cholesteryl ester
      hydrolase (rhncCEH) was used to substitute acidic, basic or neutral amino acid
      residues for Ser506, required for activation by protein kinase A. The
      substitution of acidic Asp506 resulted in esterase activities with cholesteryl
      oleate, p-nitrophenylcaprylate (PNPC) and p-nitrophenylacetate (PNPA) equivalent
      to those of native rhncCEH with Ser506. The substitution of 2 acidic residues
      (Asp505/506), emulating the 2 negative charges of phosphoserine, resulted in a 10
      fold greater cholesterol esterase activity than that of native rhncCEH, similar
      to the activity of rhncCEH treated with protein kinase A. In contrast to mutants
      with Ser506, protein kinase A did not increase the specific activities of mutants
      with Asp505/506. The substitution of basic (Lys506) or neutral (Asn506) residues
      abolished activity with cholesteryl oleate but not PNPC or PNPA. The substitution
      of neutral Gln for basic residues Lys496/Arg503 also abolished cholesterol
      esterase activity but not PNPC- and PNPA-esterase activities. These structure
      activity relationships are modeled by homology with a recently reported crystal
      structure for the homologous human triacylglycerol hydrolase. The results suggest
      that the cholesterol esterase activity of carboxylesterases is enhanced by
      interactions between one or more basic residues on helix alpha16 (residues 485
      503) and acidic groups at residues 505-506 in the adjacent surface loop.

PMID- 15866485
TI  - Increase in vulnerability to oxidative damage in cholesterol-modified
      erythrocytes exposed to t-BuOOH.
AB  - During the course of radical oxidation, cholesterol may exert seemingly
      contradictory effects. In order to gain a better understanding of the
      relationship between cholesterol levels and membrane susceptibility to oxidative
      damage induced by reactive oxygen species (ROS), here we analyze the integrity
      and structural stability of cholesterol-modified (enriched or depleted) and
      unmodified (control) erythrocytes exposed to tert-butyl hydroperoxide. The
      oxidant significantly increased ROS production, with almost complete oxidation of
      hemoglobin and a reduction in GSH content in the different erythrocyte groups at
      2 mM concentration. These changes were accompanied by losses of cholesterol and
      total phospholipids, the main decreases being in phosphatidylethanolamine and
      phosphatidylcholine. The highest lipid loss was found in the cholesterol-depleted
      group. Fatty acid analyses revealed changes only in peroxidized cholesterol
      modified erythrocytes, with decreases in linoleic and arachidonic acids.
      Fluorescence anisotropy studies showed an increase in the fluidity of the
      negatively charged surface of peroxidized control erythrocytes. Increased
      hemolysis and a positive correlation between cellular osmotic fragility and
      malondialdehyde contents were found in all peroxidized groups. These findings
      provide evidence that the modification of cholesterol levels in the erythrocyte
      membrane has provoking effects on peroxidation, with corresponding increases in
      oxidative damage in the treated cell, possibly as a consequence of lipid bilayer
      destabilization.

PMID- 15866486
TI  - Chiral liquid chromatography-tandem mass spectrometric methods for stereoisomeric
      pharmaceutical determinations.
AB  - The characterization of the drug metabolism and pharmacokinetic (DMPK) profiles
      of stereoisomers is a fundamental aspect of the drug discovery and development
      processes. Therefore, chiral drug bioassays are very important to pharmaceutical
      and biomedical researchers. The recent developments in chiral liquid
      chromatography coupled to atmospheric pressure ionization tandem mass
      spectrometry (LC-API-MS/MS) for the analysis of pharmaceuticals are reviewed.
      Various ionization techniques including electrospray ionization (ESI),
      atmospheric pressure chemical ionization (APCI) and atmospheric photoionization
      (APPI) interfaced with chiral liquid chromatographic methods are described in
      terms of their ionization efficiencies, matrix effects and limitations. Examples
      were selected to demonstrate the applicability of these methods for
      enantioselective bioanalysis.

PMID- 15866487
TI  - Association mechanism between a series of rodenticide and humic acid: a frontal
      analysis to support the biological data.
AB  - The binding constants (K) of a series of anticoagulant rodenticides with the main
      soil organic component, humic acid (HA), were determined using frontal analysis
      approach. The order of the binding constants was identical as the one obtained in
      a previous paper [J. Chromatogr. B 813 (2004) 295], i.e.
      bromadiolone>brodifacoum>difenacoum>chlorophacinone>diphacinone, confirming the
      power of this frontal analysis approach for the determination of binding
      constants. Moreover, and for the first time, the concentration of unbound
      rodenticide to HAs could be determined. Thanks this approach, we could clearly
      demonstrate that HA acid protected the human hepatoma cell line HepG2 against the
      cytotoxicity of all the rodenticides tested and that the toxicity of rodenticides
      was directly linked to the free rodenticide fraction in the medium (i.e. unbound
      rodenticide to HA).

PMID- 15866488
TI  - Gas chromatography-mass spectrometry determination of metabolites of conjugated
      cis-9,trans-11,cis-15 18:3 fatty acid.
AB  - Structural determination of polyunsaturated fatty acids by gas chromatography
      mass spectrometry (GC-MS) requires currently the use of nitrogen containing
      derivatives such as picolinyl esters, 4,4-dimethyloxazoline or pyrrolidides
      derivatives. The derivatization is required in most cases to obtain low energy
      fragmentation that allows accurate location of the double bonds. In the present
      work, the following metabolites of rumelenic (cis-9,trans-11,cis-15 18:3) acid,
      from rat livers, were identified: cis-8,cis-11,trans-13,cis-17 20:4, cis-5,cis
      8,cis-11,trans-13,cis-17 20:5, cis-7,cis-10,cis-13,trans-15,cis-19 22:5, and cis
      4,cis-7,cis-10,cis-13,trans-15,cis-19 22:6 acids by GC-MS as their 4,4
      dimethyloxazoline and methyl esters derivatives. Specific fragmentation of the
      methyl ester derivatives revealed some similarity with their corresponding DMOX
      derivatives. Indeed, intense ion fragments at m/z=M+-69, corresponding to a
      cleavage at the center of a bis-methylene interrupted double bond system were
      observed for all identified metabolites. Moreover, intense ion fragments at
      m/z=M+-136, corresponding to allylic cleavage of the n-12 double bonds were
      observed for the C20:5, C22:5, C22:6 acid metabolites. For the long chain
      polyunsaturated fatty acids from the rumelenic metabolism, we showed that single
      methyl esters derivatives might be used for both usual quantification by GC-FID
      and identification by GC-MS.

PMID- 15866489
TI  - Chiral chromatographic separation of beta-blockers.
AB  - A novel amide based chiral stationary phase m-[(+)-alpha-methyl benzyl
      carboxamide] XAD-4 has been synthesized by covalently linking R(+)-1
      phenylethylamine to chloroformoyl Amberlite XAD-4 under weak alkaline conditions.
      The synthesized resin has been primarily characterized by m.p., elemental
      analysis and FT-IR and 13C NMR spectra. beta-Blockers viz. atenolol, metoprolol,
      and propranolol were successfully separated into their enantiomers using a
      mixture of sodium acetate-acetic acid buffer (pH 4.1):acetonitrile (4:6, v/v)
      solution using the synthesized resin. Hydrogen bonding and pi-pi interactions are
      supposed to be the major analyte-chiral stationary phase interactions.

PMID- 15866490
TI  - Simultaneous determination of fluoxetine, citalopram, paroxetine, venlafaxine in
      plasma by high performance liquid chromatography-electrospray ionization mass
      spectrometry (HPLC-MS/ESI).
AB  - Fluoxetine, citalopram, paroxetine and venlafaxine have been widely used in the
      treatment of depression. However, no study has been conducted to determine the
      four drugs simultaneously by high performance liquid chromatography-electrospray
      ionization mass spectrometry (HPLC-MS/ESI). OBJECTIVE: To establish a new, rapid
      and sensitive HPLC-MS/ESI method for simultaneous determination and screening in
      human plasma of the four most commonly prescribed nontricyclic antidepressants:
      fluoxetine, citalopram, paroxetine and venlafaxine. METHODS: The analytes in
      plasma were extracted by solid-phase-extraction column after samples had been
      alkalinized. The HPLC separation of the analytes was performed on a MACHEREY
      NAGEL C(18) (250 mmx4.6 mm, 5 microm, Germany) column, using water (formic acid
      0.6 per thousand, ammonium acetate: 30 mmol/l)-acetonitrile (35:65, v/v) as
      mobile phase, with a flow-rate of 0.85 ml/min. The compounds were ionized in the
      electrospray ionization (ESI) ion source of the mass spectrometer and were
      detected in the selected ion recording (SIR) mode. RESULTS: The calibration
      curves were linear in the 5.0-1000.0 ng/ml range for all compounds, all of them
      with coefficients of determination above 0.9900. The average extraction
      recoveries for all the four analytes were above 73.2%. The methodology recoveries
      were higher than 95.0%. The limits of detection (LODs) were 0.5, 0.3, 0.3 and 0.1
      ng/ml for fluoxetine, citalopram, paroxetine and venlafaxine, respectively. The
      intra- and inter-day variation coefficients were less than 15.0%. CONCLUSION: The
      method is accurate, sensitive and simple for routine therapeutic drug monitoring
      (TDM) as well as toxicologic screening, and for the study of the pharmacokinetics
      and metabolism of the four drugs.

PMID- 15866491
TI  - Simultaneous determination of six phenolic constituents of danshen in human serum
      using liquid chromatography/tandem mass spectrometry.
AB  - The six phenolic constituents are water-soluble components extracted from the
      Chinese medical herb danshen, the dried roots of Salvia miltiorrhiza Bunge
      (Labiatae). An liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based
      method has been developed for the simultaneous quantification of six phenolic
      constituents of danshen (magnesium lithospermate B (MLB), rosmarinic acid (RA)
      and lithospermic acid (LA), caffeic acid (CAA), protocatechuic aldehyde (3,4
      dihydroxybenzaldehyde, Pal), 3,4-dihydroxyphenyllactic acid (danshensu)) in human
      serum with chloramphenicol as internal standard. The serum samples were treated
      by special liquid-liquid extraction, and the analytes were determined using
      electrospray negative ionization mass spectrometry in the multiple reaction
      monitoring (MRM) mode, with sufficient sensitivity to allow analysis of human
      serum samples generated following administration of a clinically relevant dose.
      Good linearity over the range 8-2048 ng/mL for six phenolic constituents was
      observed. The intra- and inter-day precisions (CV) of analysis were <13%, and the
      accuracy ranged from 88 to 116%. This quantitation method was successfully
      applied to a pharmacokinetic study of i.v. drip infusion of Danshen injection
      fluid in human.

PMID- 15866492
TI  - Stir bar sorptive extraction with in situ derivatization and thermal desorption
      gas chromatography--mass spectrometry for measurement of phenolic xenoestrogens
      in human urine samples.
AB  - A high-sensitivity analytical method that uses stir bar sorptive extraction
      (SBSE) with in situ derivatization and thermal desorption (TD)-gas chromatography
      mass spectrometry (GC-MS) for the simultaneous measurement of trace amounts of
      phenolic xenoestrogens (PXs), such as 2,4-dichlorophenol (DCP), 4-tert
      butylphenol (BP), 4-tert-octylphenol (OP), 4-nonylphenol technical isomers (NP),
      pentachlorophenol (PCP) and bisphenol A (BPA), in human urine samples was
      developed. The urine sample (1 ml) was de-conjugated by adding beta-glucuronidase
      and sulfatase. Then, protein precipitation was performed by the addition of
      acetonitrile. After centrifugation, the supernatant was diluted with purified
      water and subjected to SBSE with in situ derivatization and TD-GC-MS. The
      detection limits of DCP, BP, OP, NP, PCP and BPA in the urine samples were 20,
      10, 10, 50, 20 and 20 pg ml-1 (ppt), respectively. The calibration curves for PXs
      were linear and had correlation coefficients higher than 0.99. The average
      recoveries of those analytes in the urine samples were higher than 95% (RSD:
      <10%, n=6) with correction using the added surrogate standards. This simple,
      accurate, sensitive and selective method can be used in the determination of PXs
      in human urine samples.

PMID- 15866493
TI  - Evaluation of online extraction/mass spectrometry for in vivo cassette analysis.
AB  - An online extraction/mass spectrometry technique was evaluated for direct
      analysis of plasma samples. A simple user-friendly online extraction system that
      consists of two pumps, an autosampler, a six-port switching valve and a mass
      spectrometer is described. The system was controlled by the LC-MS software
      (Masslynx 3.5, Waters Corporation, Beverly, MA). Various analytical conditions
      such as extraction column, mobile phases, run time and wash solvent were
      optimized to establish an analytical method that was simple, easy to set up and
      generic. Sample preparation effort was minimal, which included dilution of plasma
      with water and centrifugation conducted in 96-well plate format. The system was
      used to analyze in vivo plasma samples from rat n-in-one cassette dosing studies.
      Concentration and pharmacokinetic (PK) data obtained from the online extraction
      method were comparable with data obtained from the protein precipitation
      extraction method. Overall, the simple, robust online extraction system provides
      cost savings by minimizing sample preparation and method development time. The
      system was used to analyze compounds from different structural classes. These
      studies suggest that calculated lipophilicity of a compound can be used as a tool
      for pre-selection of extraction column, which would save method development time
      for early discovery studies.

PMID- 15866494
TI  - Determination of an investigational HIV integrase inhibitor in human plasma using
      high performance liquid chromatography with tandem mass spectrometric detection.
AB  - An HPLC-MS/MS assay for the determination of an HIV integrase inhibitor, 5-(1,1
      dioxido-1,2-thiazinan-2-yl)-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7
      carboxamide (I) in human plasma has been developed and validated. Compound I and
      a stable isotope labeled internal standard (II) were isolated from 0.5 mL plasma
      samples by solid phase extraction using an Ansys SPEC C-8 96-well plate. Extracts
      were separated on a Hypersil BDS C-18 HPLC column (3.0 mmx50 mm, 3 microm) with a
      mobile phase consisting of 25 mM ammonium formate pH 3.0:acetonitrile (60:40)
      vol%/vol% pumped at 0.5 mL/min. A Sciex API 365 mass spectrometer equipped with
      an atmospheric pressure chemical ionization source was operated in selected
      reaction monitoring (SRM) mode with the precursor-to-product ion transitions m/z
      431-->109 (I) and m/z 437-->115 (II) used for quantitation. The assay was
      validated over the concentration range of 10-5000 ng/mL and was found to have
      acceptable accuracy, precision, linearity, and selectivity. The mean extraction
      recovery from spiked plasma samples was 69%. The intra-day accuracy of the assay
      was within 4% of nominal and intra-day precision was better than 4% C.V.
      Following a 200 mg dose of the compound administered to human subjects,
      concentrations of I ranged from 21.1 to 1500 ng/mL in plasma samples collected up
      to 12 h after dosing. Inter-day accuracy and precision results for quality
      control samples run over a 3-month period alongside clinical samples showed mean
      accuracies of within 6% of nominal and precision better than 3.5% C.V.

PMID- 15866495
TI  - Determination of ajulemic acid and its glucuronide in human plasma by gas
      chromatography-mass spectrometry.
AB  - A method using gas chromatography-mass spectrometry (GC-MS) and solid-phase
      extraction (SPE) was developed for the determination of ajulemic acid (AJA), a
      non-psychoactive synthetic cannabinoid with interesting therapeutic potential, in
      human plasma. When using two calibration graphs, the assay linearity ranged from
      10 to 750 ng/ml, and 750 to 3000 ng/ml AJA. The intra- and inter-day precision
      (R.S.D., %), assessed across the linear ranges of the assay, was between 1.5 and
      7.0, and 3.6 and 7.9, respectively. The limit of quantitation (LOQ) was 10 ng/ml.
      The amount of AJA glucuronide was determined by calculating the difference in the
      AJA concentration before ("free AJA") and after enzymatic hydrolysis ("total
      AJA"). The present method was used within a clinical study on 21 patients
      suffering from neuropathic pain with hyperalgesia and allodynia. For example,
      plasma levels of 599.4+/-37.2 ng/ml (mean+/-R.S.D., n=9) AJA were obtained for
      samples taken 2 h after the administration of an oral dose of 20 mg AJA. The mean
      AJA glucuronide concentration at 2h was 63.8+/-127.9 ng/ml.

PMID- 15866496
TI  - Liquid chromatography-electrospray mass spectrometry determination of a bis
      thiazolium compound with potent antimalarial activity and its neutral
      bioprecursor in human plasma, whole blood and red blood cells.
AB  - Liquid chromatography-electrospray ionization mass spectrometry methods are
      described for the simultaneous quantification of a bis-thiazolium compound (T3),
      its related prodrug (TE3) and an intermediate compound (mTE3) that appeared
      during the prodrug/drug conversion process, in human plasma, whole blood and red
      blood cells (RBCs). The methods involve solid phase extraction (SPE) of the
      compounds and the internal standard (verapamil) from the three different matrices
      using OasisHLB columns with an elution solvent of 2x1 ml of acetonitrile
      containing 1 ml/l trifluoroacetic acid (TFA). HPLC separation was performed on a
      C18 encapped Xterra column packed with 3.5 microm particles. The mobile phase
      used a 8 min gradient, from water containing 1 ml/l TFA to acetonitrile
      containing 1 ml/l TFA, at a flow rate of 400 microl/min. Verapamil and the TE3
      compound were characterized by the protonated molecules at m/z 455 and m/z 541,
      respectively. The mTE3 species was detected through the (M)+ ion at m/z 497. The
      T3 compound was detected by use of two ions, the quaternary ammonium salt (M2+/2)
      at m/z 227.3 and by the adduct with TFA (M+TFA)+ at m/z 567.3. The drug/internal
      standard peak area ratios were linked via a quadratic relationship to plasma (or
      whole blood) concentrations in the tested range of 6.4-1282 microg/l (12.8-2564
      microg/kg) for T3, 20-2000 microg/l (40-4000 microg/kg) for mTE3 and 10-2000
      microg/l (40-4000 microg/kg) for TE3, and to T3 concentrations in RBCs ranging
      from 12.8 to 2564 microg/kg. Inter-assay precision (in terms of R.S.D.) was below
      13.5% and accuracy ranged from 95.4 to 107%. The dilution of the samples (plasma
      or whole blood) has no influence on the performance of the methods. The
      extraction recoveries averaged 87% for T3, 53% for mTE3 and 79% for TE3 in
      plasma; 79% for T3, 57% for mTE3 and 65% for TE3 in blood; and 93% for T3 in
      RBCs, and was constant across the calibration range. The lower limits of
      quantitation were 6.4 microg/l for T3, 20 microg/l for mTE3 and 10 microg/l for
      TE3 in plasma; 12.8 microg/kg for T3 and 40 microg/kg for mTE3 and TE3 in blood;
      and 12.8 microg/kg for T3 in RBCs. Stability tests under various conditions were
      also investigated. The three-step SPE procedure (loading, clean-up, and elution)
      described in this paper to quantify these new anti-malarial compounds in plasma,
      whole blood and RBCs, can easily be automated by using either robotisation or an
      automated sample preparation system.

PMID- 15866497
TI  - Determination of dichloromethane, trichloroethylene and perchloroethylene in
      urine samples by headspace solid phase microextraction gas chromatography-mass
      spectrometry.
AB  - A method for the determination of volatile chlorinated hydrocarbons, namely
      dichloromethane (DCM), trichloroethylene (TCE), and perchloroethylene (PCE), in
      urine samples was developed using headspace solid phase microextraction (HS-SPME)
      gas chromatography-mass spectrometry (GC-MS). HS-SPME was performed using a 75
      microm Carboxen-polydimethylsiloxane fiber. Factors, which affect the HS-SPME
      process, such as adsorption and desorption times, stirring, salting-out effect,
      and temperature of sampling have been evaluated and optimized. The highest
      extraction efficiency was obtained when sampling was performed at room
      temperature (22 degrees C), from samples saturated with salt and under agitation.
      Linearity of the HS-SPME-GC-MS method was established over four orders of
      magnitude and the limit of detection was 0.005 microg/l for all the compounds.
      Precision, calculated as %R.S.D. at three different concentration levels, was
      within 1-8% for all intra- and inter-day determinations. The method was applied
      to the quantitative determination of TCE and PCE in human urine samples from
      exposed (TCE, n=5; median, 9.32 microg/l and PCE, n=39; median, 0.58 microg/l)
      and non-exposed individuals (n=120; median concentrations, 0.64, 0.22 and 0.11
      microg/l for DCM, TCE and PCE, respectively. In addition, two cases of acute
      accidental exposure to DCM are reported, and the elimination kinetics in blood
      and urine was followed up. The calculated half-lives of urinary and blood DCM
      were, respectively, 7.5 and 8.1 h for one subject and 3.8 and 4.3 h for the
      other.

PMID- 15866498
TI  - Determination of talinolol in human plasma using automated on-line solid phase
      extraction combined with atmospheric pressure chemical ionization tandem mass
      spectrometry.
AB  - A specific LC-MS/MS assay was developed for the automated determination of
      talinolol in human plasma, using on-line solid phase extraction system (prospekt
      2) combined with atmospheric pressure chemical ionization (APCI) tandem mass
      spectrometry. The method involved simple precipitation of plasma proteins with
      perchloric acid (contained propranolol) as the internal standard (IS) and
      injection of the supernatant onto a C8 End Capped (10 mmx2 mm) cartridge without
      any evaporation step. Using the back-flush mode, the analytes were transferred
      onto an analytical column (XTerra C18, 50 mmx4.6 mm) for chromatographic
      separation and mass spectrometry detection. One of the particularities of the
      assay is that the SPE cartridge is used as a column switching device and not as
      an SPE cartridge. Therefore, the same SPE cartridge could be used more than 28
      times, significantly reducing the analysis cost. APCI ionization was selected to
      overcome any potential matrix suppression effects because the analyte and IS co
      eluted. The mean precision and accuracy in the concentration range 2.5-200 ng/mL
      was found to be 103% and 7.4%, respectively. The data was assessed from QC
      samples during the validation phase of the assay. The lower limit of
      quantification was 2.5 ng/mL, using a 250 microL plasma aliquot. The LC-MS/MS
      method provided the requisite selectivity, sensitivity, robustness accuracy and
      precision to assess pharmacokinetics of the compound in several hundred human
      plasma samples.

PMID- 15866499
TI  - Affinity recovery of Moloney Murine Leukaemia Virus.
AB  - Lipid enveloped retroviruses such as Moloney Murine Leukaemia Virus (MoMuLV) are
      commonly used gene therapy vectors. Downstream processing protocols used for
      their purification are time consuming and a potentially generic, single step
      capture method for the recovery of retroviral particles is proposed that exploits
      streptavidin-biotin affinity chromatography. The ability of four conventional
      adsorbent solid phases, Fractogel, Sepharose, Magnespheres and STREAMLINE
      immobilised with streptavidin, to capture and recover biotinylated Moloney Murine
      Leukaemia Virus was studied. MoMuLV can be biotinylated whilst retaining
      infectivity and the biotinylated virus can be adsorbed to Streptavidin
      Magnespheres yielding a 2298-fold increase in titre. For optimal virus
      biotinylation purification using Fractogel streptavidin can yield a 1896-fold
      increase in cfu/mg of protein and a 1191-fold decrease in DNA/cfu. Infectious
      virus can be recovered from Fractogel streptavidin with a maximum recovery of
      16.7%.

PMID- 15866500
TI  - Rapid quantitation of plasma 2'-deoxyuridine by high-performance liquid
      chromatography/atmospheric pressure chemical ionization mass spectrometry and its
      application to pharmacodynamic studies in cancer patients.
AB  - A novel method employing high-performance liquid chromatograph-mass spectrometry
      (LC-MS) has been developed and validated for the quantitation of plasma 2'
      deoxyuridine (UdR). It involves a plasma clean-up step with strong anion-exchange
      solid-phase extraction (SAX-SPE) followed by HPLC separation and atmospheric
      pressure chemical ionization mass spectrometry detection (APCI-MS) in a selected
      ion monitoring (SIM) mode. The ionization conditions were optimised in negative
      ion mode to give the best intensity of the dominant formate adduct [M+HCOO]- at
      m/z 273. Retention times were 7.5 and 12.5 min for 2'-deoxyuridine and 5-iodo-2'
      deoxyuridine, an iodinated analogue internal standard (IS), respectively. Peak
      area ratios of 2'-deoxyuridine to IS were used for regression analysis of the
      calibration curve. The latter was linear from 5 to 400 nmol/l using 1 ml sample
      volume of plasma. The average recovery was 81.5% and 78.6% for 2'-deoxyuridine
      and 5-iodo-deoxyuridine, respectively. The method provides sufficient
      sensitivity, precision, accuracy and selectivity for routine analysis of human
      plasma 2'-deoxyuridine concentration with the lowest limit of quantitation (LLOQ)
      of 5 nmol/l. Clinical studies in cancer patients treated with the new
      fluoropyrimidine analogue capecitabine (N4-pentoxycarbonyl-5'-5-fluorocytidine)
      have shown that plasma 2'-deoxyuridine was significantly elevated after 1 week of
      treatment, consistent with inhibition of thymidylate synthase (TS). These
      findings suggest that the mechanism of antiproliferative toxicity of capecitabine
      is at least partly due to TS inhibitory activity of its active metabolite 5
      fluoro-2'-deoxyuridine monophosphate (FdUMP). Monitoring of plasma UdR
      concentrations have the potential to help clinicians to guide scheduling of
      capecitabine or other TS inhibitors in clinical trials. Marked differences of
      plasma 2'-deoxyuridine between human and rodents have also been confirmed. In
      conclusion, the LC-MS method developed is simple, highly selective and sensitive
      and permits pharmacodynamic studies of TS inhibitors in several species.

PMID- 15866501
TI  - Simultaneous detection of submicrogram quantities of hyaluronic acid and dermatan
      sulfate on agarose-gel by sequential staining with toluidine blue and Stains-All.
AB  - A new discontinuous agarose-gel electrophoresis in 0.05 M HCl/0.04 M barium
      acetate combined with the highly sensitive visualization technique using
      toluidine blue/Stains-All has been developed for the simultaneous assaying of
      hyaluronic acid (HA) and dermatan sulfate (DS) with a detection limit at
      submicrogram level greater than other conventional procedures. Furthermore, this
      procedure also separates and reveals chondroitin sulfate (CS). The densitometric
      analysis of bands resulted in a linear response between 0.01 and 0.5 microg of
      glycosaminoglycans (GAGs) with correlation coefficients greater than
      approximately 0.94. Hyaluronic acid and dermatan sulfate extracted and purified
      from the abdominal skin of six rats were separated and quantified in comparison
      with the evaluation made by treatment of chondroitin ABC lyase and separation of
      Delta-disaccharides from hyaluronic acid (DeltadiHA) and dermatan
      sulfate/chondroitin sulfate (Deltadi4s and Deltadi6s) by HPLC. The total amount
      of rat skin polysaccharides (hyaluronic acid and dermatan sulfate) was 1.24+/
      0.26 microg/mg of tissue by discontinuous agarose-gel electrophoresis and 1.20+/
      0.33 microg/mg by HPLC with hyaluronic acid and dermatan sulfate percentages of
      50.32+/-2.38 and 49.66+/-2.53, respectively. The analyses also confirmed that
      hyaluronic acid and dermatan sulfate are the main rat abdominal skin
      polysaccharides with chondroitin sulfate present in trace amounts. This new
      agarose-gel electrophoresis could be particularly useful in the study of the
      distribution of glycosaminoglycans in the skin from different body sites of
      animals and normal human subjects and may be of importance in understanding the
      changes that occur in the skin, especially the metabolism of extracellular matrix
      constituents, in connective tissue disorders.

PMID- 15866502
TI  - Evaluation of three methods for effective extraction of DNA from human hair.
AB  - In this paper we evaluate three different methods for extracting DNA from human
      hair i.e. the Chelex method, the QIAamp DNA Mini Kit method and the ISOHAIR
      method. Analysis of DNA prepared from dyed hairs with the ISOHAIR method
      suggested that the DNA extracts contained PCR inhibitors. On the other hand, few
      inhibition was observed when DNA from dyed hairs were extracted using the Chelex
      method and the QIAamp DNA Mini Kit method. In conclusion, the Chelex method is
      recommended for PCR experiments in view of its simplicity and cost-effectiveness.
      To assess the reliability of the Chelex method for the extraction of genomic DNA
      from both natural and dyed hair samples, minisatellite variant repeat (MVR)
      polymerase chain reaction (PCR) patterns of Chelex-extracted DNA were compared
      using hairs (three natural black hairs and three dyed hairs) with buccal swabs
      from six individuals. Complete agreement was observed between hair and swab
      samples in each individual, proving the utility of the Chelex method.

PMID- 15866503
TI  - A gel filtration assay to determine glycogen synthase activity.
AB  - We developed a gel filtration assay for the determination of glycogen synthase
      activity in cultured cells or tissue homogenates. Compared to the commonly used
      filter paper assay, the gel filtration assay resulted in a more than 5-fold
      reduction of background levels leading to an--at least--twofold increase in
      precision. These benefits allow the gel filtration method to detect differences
      of +/-5% in enzyme activity out of 300 microg total cell protein. In addition to
      high precision and sensitivity, the method's additional salient advantages
      include lesser expenditure of time and labour and reduced exposure time of the
      personnel to radioactivity.

PMID- 15866504
TI  - Determination of riboflavin by high-performance liquid chromatography with
      riboflavin-depleted urine as calibration and control matrix.
AB  - A simple method, exposure to natural-light, was developed to remove riboflavin
      from urine to enhance its use as the biological matrix for the preparation of
      calibration and control samples. Riboflavin-depleted urine containing less than 1
      ng/ml of riboflavin was used to validate a high-performance liquid chromatography
      with fluorescence detection method for the determination of urinary riboflavin.
      The linearity of the assay (r2=0.999) was acceptable over the range of 10-5000
      ng/ml. The intra-assay and inter-assay CVs were 3.3% and 9%, respectively.
      Subsequent stability studies found that urine riboflavin was stable for up to 6
      months at 4 or -20 degrees C.

PMID- 15866505
TI  - Application of a validated high-performance liquid chromatography-mass
      spectrometry assay to the analysis of m- and p-hydroxybenzoylecgonine in
      meconium.
AB  - A high-performance liquid chromatography (HPLC)-mass spectrometry (MS) assay,
      already validated for opiates and cocaine in meconium, has been re-applied for
      determination of m- and p-hydroxybenzoylecgonine, using nalorphine as the
      internal standard. Methodology included an initial extraction from the matrix by
      methanol and then a solid-phase extraction (SPE). A reversed-phase chromatography
      was used with a gradient of 1% acetic acid-acetonitrile coupled to atmospheric
      pressure ionization electrospray-mass spectrometry single ion monitoring mode.
      This method, validated in the range 0.005-1.00 microg analytes/g meconium, proved
      useful to identify and quantify these two metabolites in meconium samples,
      already tested for the presence of cocaine, benzoylecgonine and cocaethylene. A
      positivity of range of concentrations varied between 0.007 and 0.338 microg/g,
      confirming the importance of these two hydroxylated derivatives to monitor fetal
      exposure to cocaine.

PMID- 15866506
TI  - Morbidity and nutrition patterns of three nomadic pastoralist communities of
      Chad.
AB  - As a part of an interdisciplinary research and action programme, morbidity and
      nutritional patterns were assessed in three nomadic communities: Fulani and Arab
      cattle breeders and Arab camel breeders, of two prefectures in Chad. The
      predominant morbidity pattern of Chadian nomadic pastoralists (representing
      approximately 10% of the total population of the country) had not been documented
      so far. A total of 1092 women, men and children was examined by a physician and
      interviewed during two surveys in the dry season and one in the wet season (1999-
      2000). Participants with no complaint were rare. Pulmonary disorders (e.g.
      bronchitis) were most often diagnosed for children under 5 years of age. Of the
      adult participants, 4.6% were suspected of tuberculosis. Febrile diarrhoea
      occurred more often during the wet season when access to clean drinking water was
      precarious. Malaria was only rarely clinically diagnosed among Arabs during the
      dry season, whereas Fulani, who stayed in the vicinity of Lake Chad, were also
      affected during this period. A 24-h dietary recall showed that less Arab women
      than men consumed milk during the dry season (66% versus 92%). Malnutrition was
      only documented for 3 out of 328 children (0--14 years). Arab women in
      childbearing age had a higher proportion of children not surviving when compared
      to Fulani women (0.2 versus 0.07). This study identified several implications for
      reseach and interventions in nomadic settings. Innovative and integrated health
      services for nomads can possibly be extended to many settings as nomadic
      pastoralists have in common a similar way of life driven by the needs of their
      animals.

PMID- 15866507
TI  - pfcrt is more than the Plasmodium falciparum chloroquine resistance gene: a
      functional and evolutionary perspective.
AB  - Genetic, physiological and pharmacological studies are gradually revealing the
      molecular basis of chloroquine resistance (CQR) in the malaria parasite,
      Plasmodium falciparum. Recent highlights include the discovery of a key gene
      associated with resistance, pfcrt (Plasmodium falciparum chloroquine resistance
      transporter; PfCRT), encoding a novel transporter, and the characterization of
      global selective sweeps of haplotypes containing a K76T amino acid change within
      this protein. Little is known about the cellular mechanism by which resistant
      parasites escape the effects of chloroquine (CQ), one of the most promising drugs
      ever deployed, due in part to an unresolved mechanism of action. The worldwide
      spread of CQR argues that investigations into these mechanisms are of little
      value. We propose, to the contrary, that the reconstruction of the evolutionary
      and molecular events underlying CQR is important at many levels, including: (i)
      its potential to assist in the development of rational approaches to thwart
      future drug resistances; (ii) the stimulation of the use of CQ-like compounds in
      drug combinations for new therapeutic approaches; and (iii) the consideration of
      how the CQ-selected genome will function as the context in which current and
      future drugs will act, particularly in light of the many reports of multidrug
      resistance. The purpose of this review is to highlight, discuss and in some cases
      challenge the interpretations of recent findings on CQR. We consider the natural
      function of the PfCRT protein, the role of multiple genes and "genetic
      background" in the CQR mechanism, and the evolution of CQR in parasite
      populations. Genetic transformation techniques are improving in P. falciparum and
      continue to provide important insight into CQR. Here, we also discuss more
      subtle, yet important pharmacological approaches that may have been overlooked in
      a traditional "gene for drug resistance" way of thinking.

PMID- 15866508
TI  - Isolation of the receptor for the Amaranthus leucocarpus lectin from human T
      lymphocytes.
AB  - Amaranthus leucocarpus lectin (ALL) is specific for GalNAc, and recognizes human
      T cells. The receptor for ALL was purified from T cells using biotin-labeled
      lectin and avidin-agarose as affinity matrix. It is a 70-kDa glycoprotein,
      constituted mainly by serine, glycine, and glutamic acid; its glycosidic portion
      contains mainly GalNAc; galactose, sialic acid, mannose, and GlcNAc were
      identified at a lower proportion. By ionic strength chromatography, as well as
      double dimension electrophoresis, we identified four isoforms of the ALL
      receptor. N-terminal amino acid was blocked both in the ALL-receptor and its
      isoforms, therefore, tryptic peptides of ALL-receptor, analyzed through MALDI
      TOF, were compared with the relative values obtained from the NCBInr (ProFound
      2004/06/01) database. Our results indicated that the tryptic peptides obtained
      showed 54% homology with a DnaK-core molecular chaperone, 47% with human KIAA
      protein, and 44% with heat shock protein 8. The most frequent phenotype of the
      CD4 or CD8 ALL+ T cells was CD45RA+ CD27+; 26% of ALL+ T cells were CD25+ and 13%
      were CD69+, indicating that the glycoprotein recognized by ALL is present mainly
      on naive or quiescent T cells.

PMID- 15866509
TI  - Acquisition of a stable structure by yeast ribosomal P0 protein requires binding
      of P1A-P2B complex: in vitro formation of the stalk structure.
AB  - Saccharomyces cerevisiae ribosomal stalk consists of five proteins: P0 protein,
      with molecular mass of 34 kDa, and four small, 11 kDa, P1A, P1B, P2A and P2B
      acidic proteins, which form a pentameric complex P0-(P1A-P2B)/(P1B-P2A). This
      structure binds to a region of 26S rRNA termed GTPase-associated domain and plays
      a crucial role in protein synthesis. The consecutive steps leading to the
      formation of the stalk structure have not been fully elucidated and the function
      of individual P-proteins in the assembling of the stalk and protein synthesis
      still remains elusive. We applied an integrated approach in order to examine all
      the P-proteins with respect to stalk assembly. Several in vitro methods were
      utilized to mimic protein self-organization in the cell. Our efforts resulted in
      reconstitution of the whole recombinant stalk in solution as well as on the
      ribosomal particle. On the basis of our analysis, it can be inferred that the P1A
      P2B protein complex may be regarded as the key element in stalk formation, having
      structural and functional importance, whereas P1B-P2A protein complex is
      implicated in regulation of stalk function. The mechanism of quaternary structure
      formation could be described as a sequential co-folding/association reaction of
      an oligomeric system with P0-(P1A-P2B) protein complex as an essential element in
      the acquisition of a stable quaternary structure of the ribosomal stalk. On the
      other hand, the P1B-P2A complex is not involved in the cooperative stalk
      formation and our results indicate an increased rate of protein synthesis due to
      the latter protein pair.

PMID- 15866510
TI  - Bupropion-induced convulsions: preclinical evaluation of antiepileptic drugs.
AB  - Bupropion, a unique, non-nicotine smoking cessation aid and an effective
      antidepressant, is well known to produce seizures following overdosing in humans.
      However, the experimental background for the usefulness of antiepileptic drugs in
      the protection against bupropion-induced convulsions has not been established
      yet. Therefore, we tested if the antiepileptic drugs were able to protect mice
      against clonic convulsions induced by intraperitoneally (i.p.) administered
      bupropion in the CD97 dose (139.5 mg/kg). Among 13 tested drugs, clonazepam
      showed the greatest potency (dose-dependent full protection; ED50 = 0.06 mg/kg,
      i.p.). No signs of locomotor impairment were observed in the rotarod test after
      anticonvulsive doses of clonazepam, resulting in a broad therapeutic window and
      favorable protective index (PI) (33.3). Gabapentin produced dose-dependent
      protection against convulsions at nontoxic doses (up to 1000 mg/kg), having
      PI>29. Diazepam in a very high dose showed full protection but its PI (1.7) was
      much less favorable than that of clonazepam. The PI values for ethosuximide,
      phenobarbital and valproate were slightly higher than unity and lower than 2, and
      for topiramate and felbamate were lower than unity. Phenytoin, carbamazepine, and
      lamotrigine as well as tiagabine failed to block the convulsant effects of
      bupropion even at doses that caused severe motor impairment. Our results
      encourage clinical testing of clonazepam against seizures developing after
      bupropion overdose.

PMID- 15866512
TI  - Expression of angiotensin II type I receptor in human cirrhotic livers: Its
      relation to fibrosis and portal hypertension.

PMID- 15866511
TI  - Sand fly specificity of saliva-mediated protective immunity in Leishmania
      amazonensis-BALB/c mouse model.
AB  - Immune response of BALB/c mice to the salivary antigens of sand flies was found
      to vary with different species used, i.e. Phlebotomus papatasi, Phlebotomus
      sergenti and Lutzomyia longipalpis. Exposure of mice to bites of these sand flies
      elicits production of antibodies, which are largely specific to different saliva
      antigens previously identified as unique to the respective fly species. When
      immunized intradermally (i.d.) with salivary gland lysates (SGL) of L.
      longipalpis, BALB/c mice developed partial protective immunity against challenges
      in the contralateral ears with Leishmania amazonensis plus the gland lysates.
      Preimmunization of these mice with the lysates from the other two species was
      ineffective, further indicative of the specificity of saliva-mediated immune
      response. The partial protective immunity observed is significant, although it is
      not as dramatic as reported previously in a different sand fly-mouse model. There
      is a correlation of this immunity with a lower number of mononuclear and
      polymorphonuclear phagocytes at the site of parasite inoculation. Vector species
      specificity of this immunity implies its elicitation by unique saliva antigen-an
      issue which requires attention when designing saliva-based vaccines against
      leishmaniasis.

PMID- 15866513
TI  - Investigation of liver fibrosis in clinical practice.
AB  - The liver is composed of different hepatic fibrogenic cells: hepatic stellate
      cells, portal fibroblasts, fibroblasts of the Glisson capsule surrounding the
      liver and vascular smooth muscle cells and the second layer cells present around
      centrolobular veins. During liver disease, one or several populations of these
      cells are activated, transformed into myofibroblasts and secrete the extra
      cellular matrix. There are markers to identify hepatic stellate cells either
      quiescent (CRBP-1) or activated (alpha-smooth muscle actin). Liver biopsy, the
      current "gold-standard" to estimate liver fibrosis cannot be used anymore as a
      "gold standard". Furthermore, it is a costly procedure with adverse effects
      feared by patients and clinicians. Alternative to liver biopsy using non-invasive
      tests or technics include FibroTest-ActiTest, transient-elastography, hepatic
      vein transit time using contrast ultrasonography, magnetic resonance imaging. As
      a routine test, the FibroTest-ActiTest is a validated one for patients with
      chronic hepatitis C. The advantage of the non-invasive tests or technics is that
      they provide a rapid and quantitative estimation of fibrosis. With these new
      methods, it is possible to follow the progression of the disease and its
      regression either spontaneously or under treatment. In conclusion, clinicians
      have in their hands several painless tools to explore liver fibrosis that can be
      easily repeated.

PMID- 15866514
TI  - Identification and expression profile of the ID gene family in the rainbow trout
      (Oncorhynchus mykiss).
AB  - ID proteins are negative regulators of basic helix-loop-helix transcription
      factors governing growth and development in mammals. However, little is known
      about the ID gene function and expression in fish. We report the identification
      and characterization of two new rainbow trout ID genes (ID1D and ID2B) and extend
      our expression analyses of two previously identified ID genes (ID1A and ID2A).
      Phylogenetic analyses indicate an evolutionary relationship between ID1A and ID1D
      and between ID1B and ID1C, suggesting a mechanism of divergence throughout
      salmonid evolution. To access the expression of these genes in adult and
      developing fish, we measured the relative transcript abundance of four ID1 and
      two ID2 genes by real-time PCR. ID1 transcripts were expressed in a variety of
      tissues and the ID1 paralogues showed similar patterns of expression, whereas the
      ID2 paralogues were differentially expressed. To access the role of the ID genes
      during embryonic development, gene expression was measured at early (day 0 and
      day 2), mid (day 9 and day 18) and late (day 30 and day 50) embryonic
      development. ID1A and ID1D expression remained unchanged throughout embryonic
      development, while ID1B and ID1C were lowest during early, highest at mid, and
      decreased during late embryonic development. The ID2 transcripts revealed the
      highest expression in unfertilized eggs and day 2 embryos, and remained low
      throughout the remainder of embryonic development. The sequence analyses and gene
      expression patterns implicate gene and genome duplication in rainbow trout ID
      gene evolution and suggest an extensive role for the IDs in rainbow trout growth
      and development.

PMID- 15866515
TI  - The influence of nucleotide sequences at and near ribosome-binding site on
      translational efficiency of the Bacillus subtilis rho gene.
AB  - The Bacillus subtilis rho gene encodes the transcription termination factor Rho
      that is produced at a low level in B. subtilis cells. No typical Shine-Dalgarno
      (SD) sequence lies at an appropriate distance from the translational start site
      of rho. However, the nucleotide sequence GTGGTG present upstream of the rho
      translational start site is highly conserved among rho genes of Bacilli. Base
      substitutions at the central GG or its downstream T abolished expression of rho
      lacZ translational fusion, suggesting their importance in rho expression.
      Mutations at the relatively conserved sequence AAAG located further upstream of
      GTGGTG could also affect translational efficiency. Moreover, insertion of two or
      three nucleotides between these two conserved regions abrogated rho-lacZ
      expression, suggesting that the spacing is important. The possibility that the
      rho gene may contain a split SD sequence is discussed.

PMID- 15866516
TI  - Cloning, expression and characterization of a 46.5-kDa metallopeptidase from
      Bacillus halodurans H4 sharing properties with the pitrilysin family.
AB  - A 1242 base pair DNA fragment from Bacillus halodurans H4 isolated from alkaline
      sediments of Lake Bogoria (Kenya) coding for a potential protease was cloned and
      sequenced. The hexa-histidine-tagged enzyme was overexpressed in Escherichia coli
      and was purified in one step by immobilized-metal affinity chromatography (IMAC)
      on Ni-NTA resin. The protease (ppBH4) presents an inverted zincin motif, HXXEH,
      which defines the inverzincin family. It shares several biochemical and molecular
      properties with the clan ME family M16 metallopeptidases (pitrilysins), as well
      as with database hypothetical proteins that are potential M16 family enzymes.
      Thus, like insulysin and nardilysin, but contrary to bacterial pitrilysin, ppBH4
      is inactivated by sulfhydryl alkylating agents. On the other hand, like bacterial
      pitrilysin, ppBH4 is sensitive to reducing agents. The enzymatic activity of
      ppBH4 is limited to substrates smaller than proteins. In contrast to insulin,
      dynorphin and insulin B-chain are very good substrates for ppBH4 and several
      cleavage sites are common with those observed with well-characterized
      pitrilysins. As deduced from amino acid sequence, as well as determined by gel
      filtration and SDS-polyacrylamide gel electrophoresis, ppBH4 is an active monomer
      of 46.5 kDa. This feature distinguishes ppBH4 from all other enzymes of the
      pitrilysin family so far described whose molecular masses range from 100 to 140
      kDa.

PMID- 15866517
TI  - An improved RNA amplification procedure results in increased yield of autologous
      RNA transfected dendritic cell-based vaccine.
AB  - Use of antigen encoding RNA transfected Dendritic cells in the field of cancer
      immunotherapy has been well established. The use of RNA overcomes limitations
      inherent to other autologous DC-based vaccines as it does not require specific
      HLA haplotypes, identification and characterization of antigens, and captures the
      broadest antigen repertoire. RNA offers yet another advantage-it could be
      amplified minimizing the requirement of tumor mass for autologous vaccine
      production, and will afford the opportunity to treat patients with minimal tumor
      burden. The original procedure described for RNA amplification resulted in a
      proportion of RNA transcribed in the antisense orientation. This study also
      demonstrates that the presence of double-stranded RNA correlates with the
      presence of antisense RNA. Alternative design of oligonucleotides that removes
      sequence redundancy eliminates the formation of both antisense and double
      stranded RNA species. We provide further evidence that amplified RNA containing
      antisense and double-stranded RNA species results in lower recovery of DCs post
      transfection and maturation, presumably through sequence-specific gene silencing.
      The removal of the double-stranded species from amplified RNA results in higher
      recovery of mature autologous amplified RNA transfected dendritic cells. Higher
      DC yield will allow for reduction of cost of vaccine manufacturing and prolonged
      treatment of a patient.

PMID- 15866518
TI  - Thermostabilized ovalbumin that occurs naturally during development accumulates
      in embryonic tissues.
AB  - We have reported that ovalbumin accumulates without digestion in various tissues
      during embryonic development of the chicken. There are different types of
      ovalbumin with respect to thermal stability and one of them, which was named "HS
      ovalbumin" in the present study, was found to have a T(m) value of 83 degrees C
      and to be present dominantly in albumen, egg yolk, amniotic fluid, and serum of
      fertilized eggs. HS-ovalbumin, arising physiologically from its native form (N
      ovalbumin), is reminiscent of the previously described intermediate form
      appearing during the production processes of the so-called S-ovalbumin, which
      disappeared shortly in fertilized eggs. We showed that HS-ovalbumin is
      distinguishable from S-ovalbumin by a monoclonal antibody and also from N
      ovalbumin by the stability to heating. At the late stages of development,
      ovalbumin of amniotic fluid seems to be swallowed through pharynx, carried in the
      intestine through stomach, and absorbed in the blood. Analyses by monoclonal
      antibody and heat treatment indicated that the HS-form occupies the largest
      fraction of ovalbumin that accumulates in the embryonic tissues. The current
      findings suggest that HS-ovalbumin is crucial for embryogenesis.

PMID- 15866520
TI  - New perfluorinated polycationic dimerizable detergents for the formulation of
      monomolecular DNA nanoparticles and their in vitro transfection efficiency.
AB  - We describe the synthesis of new perfluorinated dimerizable detergents which
      contain a tricationic or tetracationic (linear or branched spermine,
      respectively) polar head, and report on their cmc, their ability to condense DNA
      into cationic monomolecular DNA nanoparticles as well as on the in vitro
      transfection efficiency of these nanoparticles. Such cationic nanoparticles were
      prone to display efficient cell transfection properties as a result of increased
      contact to the anionic cell surface and internalization by endocytosis, low size
      compatible with improved intracellular diffusion and nuclear pore crossing, and
      the presence of amine function of low pK(a) for their endosomal escape. The
      challenge was to design polymerizable polycationic detergents that display a cmc
      high enough for the monomer to perform monomolecular DNA condensation (as
      cationic particles) and low enough for the dimer to form stable nanoparticles
      capable of efficient cell transfection. Although we succeeded in formulating
      small-sized cationic monomolecular DNA nanoparticles (<40 nm) with these
      dimerizable perfluorinated spermine-based detergents for N/P ratios of up to 5
      (N=number of detergent amine equivalents/P=number of DNA phosphate equivalents),
      these small-sized cationic nanoparticles proved to be poor non-specific
      transfection agents in vitro, even in the presence of chloroquine. Their poor
      transfection potential could be due more likely to Brownian motion which prevents
      these very small-sized particles from sedimentation and adsorption onto the
      adherent cell monolayer, and, consequently, from proteoglycan-triggered
      endocytosis.

PMID- 15866519
TI  - Effect of arylformamidase (kynurenine formamidase) gene inactivation in mice on
      enzymatic activity, kynurenine pathway metabolites and phenotype.
AB  - The gene coding for arylformamidase (Afmid, also known as kynurenine formamidase)
      was inactivated in mice through the removal of a shared bidirectional promoter
      region regulating expression of the Afmid and thymidine kinase (Tk) genes.
      Afmid/Tk -deficient mice are known to develop sclerosis of glomeruli and to have
      an abnormal immune system. Afmid-catalyzed hydrolysis of N-formyl-kynurenine is a
      key step in tryptophan metabolism and biosynthesis of kynurenine-derived products
      including kynurenic acid, quinolinic acid, nicotinamide, NAD, and NADP. A
      disruption of these pathways is implicated in neurotoxicity and immunotoxicity.
      In wild-type (WT) mice, Afmid-specific activity (as measured by formyl-kynurenine
      hydrolysis) was 2-fold higher in the liver than in the kidney. Formyl-kynurenine
      hydrolysis was reduced by approximately 50% in mice heterozygous (HZ) for
      Afmid/Tk and almost completely eliminated in Afmid/Tk knockout (KO) mice.
      However, there was 13% residual formyl-kynurenine hydrolysis in the kidney of KO
      mice, suggesting the existence of a formamidase other than Afmid. Liver and
      kidney levels of nicotinamide plus NAD/NADP remained the same in WT, HZ and KO
      mice. Plasma concentrations of formyl-kynurenine, kynurenine, and kynurenic acid
      were elevated in KO mice (but not HZ mice) relative to WT mice, further
      suggesting that there must be enzymes other than Afmid (possibly in the kidney)
      capable of metabolizing formyl-kynurenine into kynurenine. Gradual kidney
      deterioration and subsequent failure in KO mice is consistent with high levels of
      tissue-specific Afmid expression in the kidney of WT but not KO mice. On this
      basis, the most significant function of the kynurenine pathway and Afmid in mice
      may be in eliminating toxic metabolites and to a lesser extent in providing
      intermediates for other processes.

PMID- 15866521
TI  - Efficacy of prolonged treatment following combination with ribavirin and
      interferon for chronic hepatitis type C: A pilot study.
AB  - The aim of the present study was to assess the efficacy of the prolonged
      interferon monotherapy following combination treatment. Seventy-six patients were
      enrolled. Of these, 7 were withdrawn while undergoing treatment with interferon
      combined with ribavirin, and 12 remained positive for HCV-RNA at the completion
      of the combination treatment. We studied 57 Japanese patients with chronic
      hepatitis C due to genotype 1b HCV of a high viral load. These patients tested
      negative for HCV-RNA at the completion of the combination treatment for 24 weeks.
      After the combination treatment, 29 patients of the prolonged treatment group
      successively received interferon-alpha monotherapy for 24 weeks, while 28
      patients in the combination treatment alone group received no medication. The
      rate of a sustained virologic response (SVR) was higher in the prolonged
      treatment group (41%, 12/29) than in the combination treatment alone group (25%,
      7/28), but not significantly. Patients who became HCV-RNA negative by 4 weeks
      after the start of the combination treatment showed an SVR rate of 86%. The
      prolonged treatment resulted in SVR in all five patients who newly became HCV-RNA
      negative at 12 weeks. In conclusion, the prolonged treatment was effective for
      patients who newly became HCV-RNA negative at 12 weeks.

PMID- 15866522
TI  - Recent advances in capillary electrophoretic immunoassays.

PMID- 15866523
TI  - A protein assay based on colloidal gold conjugates with trypsin.
AB  - The standard sol particle immunoassay (SPIA) is based on a biospecific
      aggregation of gold nanoparticle conjugates, followed by conventional
      spectrophotometry. Here we propose a novel SPIA format that uses microtitration
      immunological plates and an enzyme-linked immunosorbent assay reader. The novel
      and standard assays are exemplified by determination of immunoglobulin G by using
      15-nm colloidal gold-protein A conjugates. We also describe a novel sol particle
      trypsin assay using conjugates of gold nanoparticles with trypsin. The method is
      based on measuring spectral extinction changes caused by the addition of protein
      to a conjugate solution. The changes in the extinction spectra are presumed to be
      related to aggregation of gold nanoparticles caused by polyvalent binding of
      protein molecules to the trypsin molecules of the conjugates.

PMID- 15866524
TI  - Protein fragmentation via liquid chromatography-quadrupole time-of-flight mass
      spectrometry: the use of limited sequence information in structural
      characterization.
AB  - Fragmentation and "top-down" sequencing of intact proteins by mass spectrometry
      (MS) is most commonly performed by infusion of protein solutions into Fourier
      transform ion cyclotron resonance (FT-ICR) mass spectrometers. However, the high
      cost of this instrumentation, coupled with the need to infuse "clean" solutions
      (lacking standard biological buffers), limits broad application of this
      technique. The current study describes an alternative approach to top-down
      sequencing using in-source fragmentation on quadrupole time-of-flight (Q-Tof)
      instrumentation coupled with reversed-phase liquid chromatography (LC).
      Application of this technique to purified recombinant samples yielded protein
      fragments during routine LC-MS analysis. The presence of multiple N- and C
      terminal fragments allowed localization of structural modifications without
      proteolytic digestion. The method was extended to complex samples by using LC
      conditions that provided high-resolution protein separation. Utility of the
      method was illustrated by real-time monitoring of protein modifications occurring
      in reconstituted apoptosomes. These experiments illustrate that intact protein
      mass and limited sequence information can be obtained simultaneously on an LC
      timescale. This approach will allow a wide variety of laboratories to routinely
      apply top-down sequencing to problems in structural characterization, protein
      purification, and biomarker identification.

PMID- 15866525
TI  - Development of high-throughput assay of lethal factor using native substrate.
AB  - The design of inhibitors for anthrax lethal factor (LF) is currently of interest
      as an approach for the treatment of anthrax because LF plays a major role in the
      cytotoxicity of target cells. LF is a zinc-dependent metalloprotease that
      specifically cleaves the mitogen-activated protein kinase kinase (MKK) family.
      Current assay systems for the screening of LF inhibitor use the optimized
      synthetic peptide coupled with various kinds of fluorophores, enabling fast,
      sensitive, and robust assays suited to high-throughput screening. However,
      evidence suggests that the regions beside the cleavage site are also involved in
      specificity and proteolytic activity of LF. In the current study, we tried to
      develop a high-throughput assay for LF activity based on native substrate,
      mitogen-activated ERK kinase 1 (MEK1). The assay system relies on the enhanced
      chemiluminescence signal resulting from a specific antibody against the C
      terminal region of native substrate. A glutathione-coated multiwell plate was
      used as a solid support to immobilize the native substrate by its N-terminal
      glutathione-S-transferase moiety. Immobilized substrate increases the specificity
      and sensitivity of LF-catalyzed substrate hydrolysis compared with the solution
      phase assay. This assay system might be used to discover a wide spectrum of
      anthrax inhibitors.

PMID- 15866526
TI  - Polarographic measurement of hydrogen sulfide production and consumption by
      mammalian tissues.
AB  - The role of nitric oxide (NO) in redox cell signaling is widely accepted.
      However, the biological role of another candidate small inorganic signaling
      molecule and the subject of this study, hydrogen sulfide (H2S), is much less
      known. H2S as a reductant and nucleophile has numerous potential cellular
      targets; however, its rapid biological oxidation suggests a fleeting cellular
      existence. The challenge of accurate real-time measurement of H2S at low
      micromolar or nanomolar concentrations in biological preparations represents a
      major impediment to H2S investigations. We here demonstrate the use of a novel
      polarographic H2S sensor (PHSS) to follow rapid changes in H2S concentration in
      common buffered biological solutions with a detection limit near 10 nM. The PHSS,
      used in combination with O2 and NO sensors in multisensor respirometry, shows
      stability, a high signal-to-noise ratio, and signal specificity for H2S.
      Preparations of rat vascular tissue exhibit H2S production on the addition of
      sulfhydryl-bearing amino acid substrates and H2S consumption when supplied with
      exogenous H2S. Taken together, these findings suggest the existence of dynamic
      steady-state cellular H2S levels. The PHSS should facilitate the investigation of
      H2S biology by providing a previously unattainable continuous record of H2S under
      biologically relevant conditions.

PMID- 15866527
TI  - Preparation of novel mercury-doped silver nanoparticles film glassy carbon
      electrode and its application for electrochemical biosensor.
AB  - A novel mercury-doped silver nanoparticles film glassy carbon (Ag/MFGC) electrode
      was prepared in this study. Electrochemical behaviors of cysteine on the Ag/MFGC
      electrode were investigated by electrochemical impedance spectroscopy and cyclic
      voltammetry (CV). The results indicated that cysteine could be strongly adsorbed
      on the surface of the Ag/MFGC electrode to form a thin layer. The doped electrode
      could catalyze the electrode reaction process of cysteine, and the cysteine
      displayed a pair of well-defined and nearly reversible CV peaks at the electrode
      in an acetate buffer solution (pH 5.0). The Ag/MFGC electrode was used for
      determination of cysteine by differential pulse voltammetry. The linear range was
      between 4.0x10(-7) and 1.3x10(-5) mol/L, with a detection limit of 1.0x10(-7)
      mol/L and a signal-to-noise ratio of 3. The relative standard deviation was 2.4%
      for seven successive determinations of 1.0x10(-5) mol/L cysteine. The
      determinations of cysteine in synthetic samples and urinal samples were carried
      out and satisfactory results were obtained. Amperometric application of the
      Ag/MFGC electrode as biosensors is proposed.

PMID- 15866528
TI  - A validated liquid chromatography-mass spectrometry method for the determination
      of leukotrienes B4 and B5 produced by stimulated human polymorphonuclear
      leukocytes.
AB  - A validated high-performance liquid chromatography (HPLC)-mass spectrometry
      method has been developed for the simultaneous assay of leukotrienes (LTs) B4 and
      B5, derived from omega-6 arachidonic acid and omega-3 polyunsaturated fatty acids
      (PUFA), respectively, produced by human polymorphonuclear leukocytes (PMNLs)
      stimulated with calcium ionophore A23187. The HPLC separation of PMNL ether
      extracts was performed on a reversed-phase column using a gradient elution
      program of 15 mM ammonium acetate and MeOH. Detection was performed by
      electrospray ionization-single quadripole mass spectrometry using single ion
      reaction monitoring in the negative mode at m/z 333.3 [M-H](-) and m/z 335.2 for
      prostaglandin B2/LTB5 and LTB4, respectively. The calibration curves for LTB4 and
      LTB5 were linear over the ranges 165-990 and 0.825-13.2 ng/ml, respectively. The
      lower limit of quantification for LTB5 was 0.66 ng/ml. The mean absolute
      recoveries for LTB4 and LTB5 were 81+/-4.8% and 82+/-5.9%, respectively. The
      method is precise with mean interday CVs for LTB4 and LTB5 within 7.1-10.7, and
      3.8-9.4%, respectively, and accurate (range of interday deviations for LTB4 and
      LTB5 were -7.8 to 1, and -5 to 9% , respectively). The method has been validated
      and is being applied to the simultaneous quantification of the leukotrienes B4
      and B5 in stimulated PMNLs in a clinical protocol studying the influence of a
      diet enriched in omega-3 PUFA on various surrogate markers of inflammation in
      young cystic fibrosis patients.

PMID- 15866529
TI  - Baroresistant buffer mixtures for biochemical analyses.
AB  - Hydrostatic pressure is a useful tool in the study of varied fields such as
      protein aggregation, association, folding, ligand binding, and allostery.
      Application of pressure can have a significant effect on the pK(a) values of
      buffers commonly used for biochemical analysis. Consequently, cationic buffers,
      rather than neutral ones, are generally used to minimize pH effects; however,
      even with these buffers, the change in pH over 3 kbar may be consequential in
      highly pH-sensitive biochemical systems. Using fluorescence-based assays, we have
      systematically examined the effects of pressure on various buffers in the neutral
      pH range. We show that many commonly used cationic and Good's buffers increase in
      pH with pressure on the order of 0.1 to 0.3 pH units/kbar, in agreement with
      other published values. Carboxylates and phosphate decrease in pH to a similar
      extent. Buffer mixtures, composed of both cationic and carboxylate or phosphate
      components, are shown to be an order of magnitude less pressure sensitive than
      the individual component buffers. Using various relative concentrations of Tris
      and either phosphate, tricarballylate (1,2,3-propanetricarboxylate), or CDA (1,1
      cyclohexane diacetate) at pH values between 7 and 8 yields baroresistant buffer
      mixtures. Buffer mixtures can be optimized for a specific pH, and a list of
      mixtures is presented for general laboratory use.

PMID- 15866530
TI  - MagSNiPer: a new single nucleotide polymorphism typing method based on single
      base extension, magnetic separation, and chemiluminescence.
AB  - We have developed a new method for typing single nucleotide polymorphisms (SNPs),
      MagSNiPer, based on single base extension, magnetic separation, and
      chemiluminescence. Single base nucleotide extension reaction is performed with a
      biotinylated primer whose 3' terminus is contiguous to the SNP site with a tag
      labeled ddNTP. Then the primers are captured by magnetic-coated beads with
      streptavidin, and unincorporated labeled ddNTP is removed by magnetic separation.
      The magnetic beads are incubated with anti-tag antibody conjugated with alkaline
      phosphatase. After the removal of excess conjugates by magnetic separation, SNP
      typing is performed by measuring chemiluminescence. The incorporation of labeled
      ddNTP is monitored by chemiluminescence induced by alkaline phosphatase.
      MagSNiPer is a simple and robust SNP typing method with a wide dynamic range and
      high sensitivity. Using MagSNiPer, we could perform SNP typing with as little as
      10(-17) mol of template DNA.

PMID- 15866531
TI  - A method for determination of phosphatidylethanol from high density lipoproteins
      by reversed-phase HPLC with TOF-MS detection.
AB  - Phosphatidylethanol (PEth) is a unique phospholipid that is formed in the body
      only in the presence of ethanol. According to a new hypothesis, blood high
      density lipoprotein (HDL) particles may act as carriers of PEth and mediate part
      of the antiatherogenic effects of moderate alcohol drinking. Liquid
      chromatographic method using reversed-phase C8 column and negative ion mode
      electrospray ionization-mass spectrometry detection with time-of-flight (TOF)
      instrument was developed for the determination of very small amounts of PEth that
      might be present on blood HDL particles. The samples used in the current study
      were human HDL spiked with PEth and internal standard phosphatidylpropanol
      (PProp). The use of reversed-phase column enabled a short analysis time of 19
      min/injection, which is only one-third of the earlier normal-phase methods
      reported. Because of the narrow bore column (2.1 mm i.d.) and short analysis
      time, the solvent consumption was decreased. The sensitivity of detection
      obtained with TOF-MS was better than that of previous methods, with the detection
      limit being as low as 1 ng/ml in injected sample (20 pg on-column approximately
      28 fmol PEth), corresponding to approximately 6.7 ng of PEth in milliliter of
      unprepared HDL. Good linearity of detection was obtained for a range of 1-100
      ng/ml of PEth, whereas all of the deviations in precision and accuracy were less
      than 15%.

PMID- 15866532
TI  - Electroimmobilization of proinsulin C-peptide to a quartz crystal microbalance
      sensor chip for protein affinity purification.
AB  - Proinsulin C-peptide was electroimmobilized to a quartz crystal microbalance
      sensor chip, localizing this low-pI peptide for covalent attachment to activated
      surface carboxyl groups. The resulting chip was used in a continuous flow
      biosensor to capture anti-C-peptide antibodies, which could subsequently be
      eluted in 5% formic acid between air bubbles for efficient recovery and mass
      spectrometric identification. The method is reproducible through repeated cycles,
      providing affinity purification of proteins under real-time monitoring of the
      binding and elution processes.

PMID- 15866533
TI  - Kinetic measurements and mechanism determination of Stf0 sulfotransferase using
      mass spectrometry.
AB  - Mycobacterial carbohydrate sulfotransferase Stf0 catalyzes the sulfuryl group
      transfer from 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to trehalose. The
      sulfation of trehalose is required for the biosynthesis of sulfolipid-1, the most
      abundant sulfated metabolite found in Mycobacterium tuberculosis. In this paper,
      an efficient enzyme kinetics assay for Stf0 using electrospray ionization (ESI)
      mass spectrometry is presented. The kinetic constants of Stf0 were measured, and
      the catalytic mechanism of the sulfuryl group transfer reaction was investigated
      in initial rate kinetics and product inhibition experiments. In addition, Fourier
      transform ion cyclotron resonance (FT-ICR) mass spectrometry was employed to
      detect the noncovalent complexes, the Stf0-PAPS and Stf0-trehalose binary
      complexes, and a Stf0-3'-phosphoadenosine 5'-phosphate-trehalose ternary complex.
      The results from our study strongly suggest a rapid equilibrium random sequential
      Bi-Bi mechanism for Stf0 with formation of a ternary complex intermediate. In
      this mechanism, PAPS and trehalose bind and their products are released in random
      fashion. To our knowledge, this is the first detailed mechanistic data reported
      for Stf0, which further demonstrates the power of mass spectrometry in
      elucidating the reaction pathway and catalytic mechanism of promising enzymatic
      systems.

PMID- 15866534
TI  - Rapid simultaneous determination of metabolic clearance of multiple compounds
      catalyzed in vitro by recombinant human UDP-glucuronosyltransferases.
AB  - The purpose of this study was to test the applicability of n-in-one (cocktail)
      incubations in the determination of intrinsic clearance (Cl(int)) as the slope of
      the linear portion of the Michaelis-Menten curve (velocity V vs. substrate
      concentration [S]) where substrate concentrations were low. A rapid, sensitive,
      and selective liquid chromatography tandem mass spectrometry (LC/MS/MS) method
      was developed for the analysis of samples produced by single-substrate and n-in
      one (seven substrates: entacapone, 17beta-estriol, umbelliferone, 4
      methylumbelliferone, tolcapone, hydroxyquinoline, and paracetamol) incubations
      conducted in 96-well plates with different recombinant UDP
      glucuronosyltransferases (UGTs). The Cl(int) values obtained with n-in-one
      incubations were compared with those obtained in single-compound incubations and
      with V(max)/K(m) values determined by estimating the enzyme kinetic parameters
      V(max) and K(m) from the Michaelis-Menten curve. When substrate concentrations
      were well below their K(m) values, Cl(int) values determined as the slope of the
      linear part of the Michaelis-Menten fitting correlated well with the values
      determined as V(max)/K(m) ratios from the Michaelis-Menten curve. The correlation
      between Cl(int) values determined in single-substrate and n-in-one incubations
      was high as well. Together, the n-in-one incubations, the determination of
      Cl(int) values as the slope of the linear part of the Michaelis-Menten fitting,
      and LC/MS/MS as an analytical method proved to be effective approaches for
      increasing throughput in the first-phase screening of metabolic properties.

PMID- 15866535
TI  - Insights into the reaction of beta-lactam antibiotics with copper(II) ions in
      aqueous and micellar media: kinetic and spectrometric studies.
AB  - Degradation of beta-lactam antibiotics by means of metallic cations seems to have
      a very complex chemistry, involving not only the catalytic effect of the metal
      ion but also complex formation. Many different compounds, such as
      methylpyrazines, oxazolones, penicilloic, penicillenic, and penicillonic acids,
      have been reported as degradation products of such antibiotics, although not many
      details about the progress of the reaction can be found in the literature. Two
      novel fluorimetric and spectrophotometric methods previously published by the
      authors, as well as kinetic studies, have been used to propose a possible
      reaction mechanism for the ampicillin degradation in the presence of copper(II)
      ions. Likewise, we have proposed the chemical structure required by the beta
      lactam antibiotics to develop absorption or fluorescence properties. Kinetics in
      micellar and aqueous media shows that the copper-ampicillin reaction proceeds
      through different pathways depending on the reaction medium.

PMID- 15866536
TI  - Metal-catalyzed oxidation reactions and mass spectrometry: the roles of ascorbate
      and different oxidizing agents in determining Cu-protein-binding sites.
AB  - Further study has been made of metal-catalyzed oxidation (MCO) reactions and mass
      spectrometry as a method to determine the binding site of copper in
      metalloproteins. The role of ascorbate and a variety of oxidizing agents,
      including O2, H2O2, and S2O8(2-), have been investigated using Cu/Zn superoxide
      dismutase (SOD) as a model system. Ascorbate is found to play two competing roles
      in the MCO reactions. It reduces Cu(II), which initiates and maintains the
      generation of reactive oxygen species, and it scavenges radicals, which helps to
      localize oxidation products to amino acids near the metal center. An ascorbate
      concentration of 100 mM is found to be optimal with regard to localizing
      oxidation products to only the Cu-binding residues (His44, His46, His61, and
      His118) of Cu/Zn SOD. This concentration of ascorbate is very similar to the
      optimum concentration found in our previous studies of different Cu-binding
      proteins. Another notable result from this study is the observation that S2O8(2-)
      is more effective as an oxidant than O2 or H2O2 in the MCO reactions. Because
      S2O8(2-) is more stable in solution than H2O2, using it as an oxidizing agent
      results in much less nonspecific oxidation to the protein. The overall results of
      this study suggest that general MCO reaction conditions may exist for determining
      the metal-binding site of a wide range of Cu-binding proteins.

PMID- 15866537
TI  - RNA constitution and estrogen-responsive gene expression in the ovariectomized
      rat uterus.
AB  - Because reproductive tracts in ovariectomized rodents, which are commonly used in
      endocrinological studies, exhibit drastic changes in response to exogenous
      estrogens, quantitative evaluation of gene expression requires extra caution. We
      found that the whole mRNA content of total RNA in the uterus of the
      ovariectomized rat was dose-dependently reduced by treatment with 17alpha
      ethynylestradiol (EE) for 3 consecutive days. Because of the decline in the ratio
      of mRNA/total RNA, real-time reverse transcriptase-polymerase chain reaction
      analysis seemingly showed that the relative ratios of the levels of stable RNAs,
      rRNA18S, rRNA5S, and tRNA-Gly, to whole mRNA were increased by EE. These results
      indicate that applying a fixed concentration of total RNA and stable RNA as an
      internal control to uterine mRNA quantification should be reconsidered. On the
      other hand, the beta-actin gene showed the most stable expression among the
      housekeeping genes examined. Using beta-actin mRNA as an internal control, we
      observed that tissue inhibitor of metalloproteinase-3 (TIMP3) mRNA was dose
      dependently reduced 24 h after treatment with EE or bisphenol A for 3 days.
      Continued investigation of TIMP3 with an appropriate internal control may be
      helpful in elucidating the mechanisms involved in uterine activation.

PMID- 15866538
TI  - RecA-mediated multistrand formation for cloning PCR products into vectors:
      simplified process for 5'-rapid amplification of cDNA ends.
AB  - I have developed a novel rapid amplification of cDNA ends (RACE) technology that
      uses multistranded DNA formation mediated by the RecA protein. Multistranded DNA
      can readily be formed at the terminus of double-stranded DNA by a complementary
      single-stranded DNA in the presence of RecA and exonuclease I. The possibility of
      applying this finding to the direct cloning of a 5'-RACE product onto a cDNA
      fragment, which does not require the use of restriction endonucleases, was
      explored. The results show that the terminal multistranded structure formed by
      the RecA-mediated reaction can be applied to RACE systems. Modifications to the
      RACE protocol to improve the effectiveness of the technique are also suggested.

PMID- 15866539
TI  - Evaluation of alkoxyresorufins as fluorescent substrates for cytochrome P450 BM3
      and site-directed mutants.
AB  - In this study, the first fluorescent assay for bacterial cytochrome P450 BM3
      (BM3) and mutants is described. BM3 mutants are potentially very versatile
      biocatalysts for the production of fine chemicals. A fluorescent assay would be
      very useful for the identification of nonnatural ligands in high-throughput
      inhibition assays. Because of the ease and sensitivity of alkoxyresorufin O
      dealkylation assays, four different alkoxyresorufins were evaluated as
      substrates. Wild-type BM3 showed extremely low activity toward all four
      alkoxyresorufins tested. Five different BM3 mutants were constructed, carrying
      different combinations of mutations R47L, F87V, and L188Q, which were previously
      shown to increase activity toward nonnatural substrates. For all mutants, a high
      benzyloxyresorufin O-dealkylation (BROD) activity was found. The triple mutant of
      BM3, R47L/F87V/L188Q, showed the highest activity, increasing 900-fold compared
      to wild-type BM3. The BROD assay could also be applied in whole Escherichia coli
      cells; permeabilization by lipopolysaccharide deficiency strongly increased
      activity. To demonstrate the applicability of the BROD assay to screening for
      novel ligands of BM3 R47L/F87V/L188Q, a library of 45 drug-like compounds was
      tested for inhibition. Of these compounds, 8 showed strong inhibition of the BROD
      activity, demonstrating for the first time that drug-like molecules also can bind
      with high affinity to BM3 mutants.

PMID- 15866540
TI  - Calcium enhances the transfection potency of stabilized plasmid-lipid particles.
AB  - Previous work from this laboratory has shown that plasmid DNA can be encapsulated
      in small (70-nm-diameter) stabilized plasmid-lipid particles (SPLP) that consist
      of a single plasmid encapsulated within a bilayer lipid vesicle. SPLP
      preferentially transfect tumor tissue following intravenous administration.
      Although the levels of transgene expression in vivo are greater for SPLP than can
      be achieved with naked DNA or complexes, they are lower than may be required for
      therapeutic benefit. In the present work we examine whether Ca2+ can enhance the
      transfection potency of SPLP. It is shown that Ca2+ can enhance SPLP transfection
      potency in bovine hamster kidney cells by 60- to 100-fold when treated in serum
      containing medium and an additional 60-fold when serum is absent for the initial
      10 min of the transfection period. When cells are treated with SPLP in the
      presence of Ca2+, there is a fivefold increase in intact plasmid in the cell. It
      is also shown that this Ca2+ effect involves the formation of calcium phosphate
      precipitates; however, these precipitates are not directly associated with the
      SPLP plasmid DNA. The ability of calcium phosphate to facilitate delivery of
      other macromolecules without direct association is also demonstrated by the
      release of large-molecular-weight dextrans from endosomal/lysosomal compartments
      in the presence of calcium phosphate. Finally, it is shown that, unlike naked
      DNA, SPLP transfection potency in the presence of calcium phosphate is not
      affected by nuclease activity.

PMID- 15866541
TI  - A fluorescence resonance energy transfer-based probe to monitor nucleosome
      structure.
AB  - Nucleosomes are the basic units of eukaryotic chromatin structure. By restricting
      factor access to regulatory DNA sequences, nucleosomes significantly impact
      genomic processes such as transcription, and various mechanisms to alter
      nucleosome structure to relieve this repression have evolved. Both nucleosomes
      and processes that alter them are inherently dynamic in nature. Thus, studies of
      dynamics will be necessary to truly understand these relief mechanisms. We
      describe here the characteristics of a novel fluorescence resonance energy
      transfer-based reporter that can clearly signal the formation of a canonical
      nucleosome structure and follow conformational and compositional changes in that
      structure, both at the ensemble-average (bulk) and at the single molecule level.
      Labeled nucleosomes behave conformationally and thermodynamically like typical
      nucleosomes; thus they are relevant reporters of nucleosome behavior. Nucleosomes
      and free DNA are readily distinguishable at the single-molecule level. Thus,
      these labeled nucleosomes are well suited to studies of dynamic changes in
      nucleosome structure including single-molecule dynamics.

PMID- 15866542
TI  - In vitro degradation of the antimicrobial human peptide HEM-gamma 130-146 in
      plasma analyzed by a validated quantitative LC-MS/MS procedure.
AB  - In stability studies during preclinical drug development, the human antimicrobial
      peptide hHEM-gamma 130-146 shows progressive N-terminal degradation in plasma. To
      determine this effect, we developed and validated a selective and quantitative
      muHPLC-MS/MS procedure for this compound. Following deproteinization by
      precipitation, reversed-phase separation is performed with a time-saving two
      column design online coupled to an ion trap mass spectrometer for electrospray
      ionization MS detection. Using a linear calibration curve obtained with synthetic
      external standards ranging nearly two orders of magnitude, we achieved good
      precision (repeatability and reproducibility: 5-15%), accuracy (-3 to 15%), and
      ruggedness with a lower limit of quantification at 0.29 microg/ml plasma (0.15
      microM). Because of good linearity (r2>0.999), the recovery (84+/-3%) and ion
      suppression (86+/-4% remaining intensity) were calculated from specifically
      prepared calibration curves. The developed procedure was applied to human and
      animal plasma samples. Incubations in the presence and absence of proteinase
      inhibitors revealed at least an aminopeptidase M activity for the initial N
      terminal truncation of tryptophan (W130) and a putative glutaminyl-peptide
      cyclotransferase activity for the resulting intermediate starting with the bared
      glutamine residue (Q131). The calculated periods of half-change demonstrated
      exceeding interspecies variations, whereas the intraspecies variations were only
      between 20 and 30%. The current procedure is valuable as a generic method for
      pharmaceutical purposes, and data give important information for further
      development toward a potential natural drug candidate.

PMID- 15866543
TI  - Sequence saturation mutagenesis with tunable mutation frequencies.

PMID- 15866544
TI  - Fluorescent assay for studying the substrate specificity of neuraminidase.

PMID- 15866545
TI  - Ability of thrombin to act as molecular chaperone, inducing formation of
      quadruplex structure of thrombin-binding aptamer.

PMID- 15866546
TI  - Activity and connectivity of brain mood regulating circuit in depression: a
      functional magnetic resonance study.
AB  - BACKGROUND: Functional imaging studies indicate that imbalances in cortico-limbic
      activity and connectivity may underlie the pathophysiology of MDD. In this study,
      using functional Magnetic Resonance Imaging (fMRI), we investigated differences
      in cortico-limbic activity and connectivity between depressed patients and
      healthy controls. METHODS: Fifteen unmedicated unipolar depressed patients and 15
      matched healthy subjects underwent fMRI during which they first completed a
      conventional block-design activation experiment in which they were exposed to
      negative and neutral pictures. Next, low frequency blood oxygenation dependent
      (BOLD) related fluctuations (LFBF) data were acquired at rest and during steady
      state exposure to neutral, positive and negative pictures. LFBF correlations were
      calculated between anterior cingulate cortex (ACC) and limbic regions--amygdala
      (AMYG), pallidostriatum (PST) and medial thalamus (MTHAL) and used as a measure
      of cortico-limbic connectivity. RESULTS: Depressed patients had increased
      activation of cortical and limbic regions. At rest and during exposure to
      neutral, positive, and negative pictures cortico-limbic LFBF correlations were
      decreased in depressed patients compared to healthy subjects. CONCLUSIONS: The
      finding of increased activation of limbic regions and decreased LFBF correlations
      between ACC and limbic regions is consistent with the hypothesis that decreased
      cortical regulation of limbic activation in response to negative stimuli may be
      present in depression.

PMID- 15866547
TI  - Reduced sustained brain activity during processing of positive emotional stimuli
      in major depression.
AB  - BACKGROUND: This study examines the directionality and temporal specificity of
      brain activity during sustained processing of emotional stimuli in individuals
      with current major depressive disorder (MDD) and nondepressed control
      participants. METHODS: Slow wave (SW) components of the event-related brain
      potential (ERP) were recorded from 16 control participants and 15 participants
      with MDD during a working memory task. During the task, individuals were shown a
      positive, neutral, or negative word and were asked to maintain it in memory for 5
      sec. Participants then saw a letter and had to decide whether it was a part of
      the previously presented word. The ERP components were measured from nine scalp
      sites (F3, Fz, F4, C3, Cz, C4, P3, Pz, P4) during the encoding of emotional
      words. RESULTS: Compared with control individuals, MDD participants exhibited
      decreased brain responses to positive relative to negative or neutral stimuli.
      This decrease in brain activity during processing of positive information was
      evident across all sites and SW components. CONCLUSIONS: Our findings suggest
      that cognitive deficits in MDD may stem from diminished brain responses during
      processing of positive information and may not be associated with an augmented
      response to negative stimuli.

PMID- 15866548
TI  - The breakpoint cluster region gene on chromosome 22q11 is associated with bipolar
      disorder.
AB  - BACKGROUND: Although the pathogenesis of bipolar disorder remains unclear,
      heritable factors have been shown to be involved. The breakpoint cluster region
      (BCR) gene is located on chromosome 22q11, one of the most significant
      susceptibility loci in bipolar disorder linkage studies. The BCR gene encodes a
      Rho GTPase activating protein, which is known to play important roles in neurite
      growth and axonal guidance. METHODS: We examined patients with bipolar disorder
      (n = 171), major depressive disorder (n = 329) and controls (n = 351) in Japanese
      ethnicity for genetic association using eleven single nucleotide polymorphisms
      (SNPs), including a missense one (A2387G; N796S), in the genomic region of BCR.
      RESULTS: Significant allelic associations with bipolar disorder were observed for
      three SNPs, and associations with bipolar II disorder were observed in ten SNPs
      including N796S SNP (bipolar disorder, p = .0054; bipolar II disorder p = .0014).
      There was a significant association with major depression in six SNPs. S796
      allele carriers were in excess in bipolar II patients (p = .0046, odds ratio =
      3.1, 95% CI 1.53-8.76). Furthermore, we found a stronger evidence for association
      with bipolar II disorder in a multi-marker haplotype analysis (p = .0002).
      CONCLUSIONS: Our results suggest that genetic variations in the BCR gene could
      confer susceptibility to bipolar disorder and major depressive disorder.

PMID- 15866549
TI  - Volume reduction in prefrontal gray matter in unsuccessful criminal psychopaths.
AB  - BACKGROUND: Although studies of neurologic patients have suggested that
      prefrontal structural impairments may predispose to sociopathy, it is unknown
      whether there is a relationship between psychopathy and prefrontal volume in
      individuals from the community and whether any prefrontal structural impairment
      is specific to "unsuccessful" (caught) psychopaths as opposed to "successful"
      (uncaught) psychopaths. This study tests the hypothesis that psychopathy is
      associated with a reduction in prefrontal gray volume but that this abnormality
      is specific to unsuccessful psychopaths. METHOD: Prefrontal gray and white matter
      volumes were assessed using structural magnetic resonance imaging (MRI) in 16
      unsuccessful psychopaths, 13 successful psychopaths, and 23 control subjects.
      RESULTS: Higher total as well as subfactor psychopathy scores
      (arrogant/deceptive, affective, and impulsive/unstable) were all associated with
      low prefrontal gray volume. Unsuccessful psychopaths, but not successful
      psychopaths, had a 22.3% reduction in prefrontal gray matter volume compared with
      control subjects. CONCLUSIONS: These results demonstrating for the first time a
      prefrontal structural deficit in community psychopaths provide partial support
      for a prefrontal theory of psychopathy but highlight an important difference
      between successful and unsuccessful psychopaths.

PMID- 15866550
TI  - Mood and hormone responses to psychological challenge in adolescent males with
      conduct problems.
AB  - BACKGROUND: Relations between stress hormones and antisocial behavior are
      understudied. METHODS: A subsample (n = 335) of at-risk males recruited in first
      grade for a longitudinal study were recruited at approximately 16 years of age
      for a laboratory study, including two psychological challenges: describing their
      worst experience on videotape, and a task in which a loud tone could be avoided.
      Measures of affect, urine, and saliva were collected multiple times before and
      after challenges. RESULTS: Negative affect increased following the worst-event
      challenge and decreased following the avoidance challenge. Mean conduct problems
      (CP) across ages 7-17 years were positively related to negative affect and
      inversely related to positive affect. CP were inversely related to post-challenge
      urinary epinephrine (E) levels when baseline E and potential confounds were
      controlled. Cortisol concentrations in saliva collected soon after the first
      challenge were positively related to CP in a post hoc subset of youths with
      extreme CP. CONCLUSIONS: Key findings A) associated persistent CP with more
      negative affectivity and less positive affectivity, B) replicated and extended
      prior findings of an inverse association of CP and urinary E, and C) suggested
      provocative hypotheses for future study relating CP, trauma history, trauma
      recall, and cortisol reactivity.

PMID- 15866551
TI  - Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a
      functional polymorphism in the catechol-O-methyltransferase gene: longitudinal
      evidence of a gene X environment interaction.
AB  - BACKGROUND: Recent evidence documents that cannabis use by young people is a
      modest statistical risk factor for psychotic symptoms in adulthood, such as
      hallucinations and delusions, as well as clinically significant schizophrenia.
      The vast majority of cannabis users do not develop psychosis, however, prompting
      us to hypothesize that some people are genetically vulnerable to the deleterious
      effects of cannabis. METHODS: In a longitudinal study of a representative birth
      cohort followed to adulthood, we tested why cannabis use is associated with the
      emergence of psychosis in a minority of users, but not in others. RESULTS: A
      functional polymorphism in the catechol-O-methyltransferase (COMT) gene moderated
      the influence of adolescent cannabis use on developing adult psychosis. Carriers
      of the COMT valine158 allele were most likely to exhibit psychotic symptoms and
      to develop schizophreniform disorder if they used cannabis. Cannabis use had no
      such adverse influence on individuals with two copies of the methionine allele.
      CONCLUSIONS: These findings provide evidence of a gene x environment interaction
      and suggest that a role of some susceptibility genes is to influence
      vulnerability to environmental pathogens.

PMID- 15866552
TI  - Naltrexone and disulfiram in patients with alcohol dependence and comorbid
      psychiatric disorders.
AB  - BACKGROUND: Disulfiram and naltrexone are approved by the Food and Drug
      Administration (FDA) for the treatment of alcoholism, but these agents have not
      been rigorously evaluated in dually diagnosed individuals. METHOD: Two-hundred
      and fifty-four patients with an Axis I psychiatric disorder and comorbid alcohol
      dependence were treated for 12 weeks in an outpatient medication study conducted
      at three Veterans Administration outpatient clinics. Randomization included
      assignment to one of four groups: 1) naltrexone alone; 2) placebo alone; 3) (open
      label) disulfiram and (blinded) naltrexone; or 4) (open-label) disulfiram and
      (blinded) placebo. Medication compliance was evaluated using the Microelectric
      Events Monitoring System. Primary outcomes were measures of alcohol use.
      Secondary outcomes included psychiatric symptoms, alcohol craving, g-GGT levels
      and adverse events. RESULTS: There was a high rate of abstinence across groups.
      Subjects treated with an active medication had significantly more consecutive
      weeks of abstinence and less craving than those treated with placebo, but there
      were no significant group differences in other measures of alcohol consumption.
      There was no advantage of the combination of both medications. CONCLUSIONS: These
      data suggest a modest advantage for the use of disulfiram and naltrexone for this
      group of dually diagnosed alcohol-dependent individuals but did not suggest an
      advantage in the combination.

PMID- 15866553
TI  - Sensitized attentional performance and Fos-immunoreactive cholinergic neurons in
      the basal forebrain of amphetamine-pretreated rats.
AB  - BACKGROUND: The consequences of repeated exposure to psychostimulants have been
      hypothesized to model aspects of schizophrenia. This experiment assessed the
      consequences of the administration of an escalating dosing regimen of amphetamine
      (AMPH) on attentional performance. Fos-like immunoreactivity (Fos-IR) in selected
      regions of these rats' brains was examined to test the hypothesis that AMPH
      sensitized attentional impairments are associated with increased recruitment of
      basal forebrain cholinergic neurons. METHODS: Rats were trained in a sustained
      attention task and then treated with saline or in accordance with an escalating
      dosing regimen of AMPH (1-10 mg/kg). Performance was assessed during the
      pretreatment and withdrawal periods and following the subsequent administration
      of AMPH "challenges" (.5, 1.0 mg/kg). Brain sections were double-immunostained to
      visualize Fos-IR and cholinergic neurons. RESULTS: Compared with the acute
      effects of AMPH, AMPH "challenges," administered over 2 months after the
      pretreatment was initiated, resulted in significant impairments in attentional
      performance. In AMPH-pretreated and -challenged animals, an increased number of
      Fos-IR neurons was observed in the basal forebrain. The majority of these neurons
      were cholinergic. CONCLUSIONS: The evidence supports the hypothesis that
      abnormally regulated cortical cholinergic inputs represent an integral component
      of neuronal models of the attentional dysfunctions of schizophrenia.

PMID- 15866554
TI  - A developmental influence of the N-methyl-D-aspartate receptor NR3A subunit on
      prepulse inhibition of startle.
AB  - BACKGROUND: The N-methyl-D-aspartate (NMDA) receptor is composed of various
      conformations of multiple subunits (including NR1, NR2A-D, and NR3A-B). Peak
      expression of the NR3A subunit occurs approximately 2-3 weeks postnatal, with low
      levels in adulthood. In the brain, the NR3A subunit is localized primarily in the
      amygdala, hippocampus, striatum, and cortex. These regions are involved in the
      modulation of prepulse inhibition of startle (PPI), an operational measure of
      sensorimotor gating that is modulated by NMDA receptors. NR3A reduces NMDA
      current in native neurons expressing NR1 and NR2 subunits and forms glycine
      receptors when expressed with NR1 in the absence of NR2 in both oocyte and
      mammalian expression systems. METHODS: To examine the role of NR3A in vivo, NR3A
      knockout (KO), and overexpressing transgenic mice were generated. Adult NR3A
      overexpressing mice exhibited normal PPI; PPI in NR3A KO mice was tested
      repeatedly from weaning through adulthood. RESULTS: Male NR3A KO mice exhibited
      an increase in PPI at 3 and 4 weeks postnatal, whereas female NR3A KO mice did
      not differ from their WT counterparts at any age tested. CONCLUSIONS: This sex
      specific increase in PPI is consistent with the antagonistic role of the NR3A
      subunit in NMDA receptor function and with the observation that estrogen
      modulates NMDA receptor function.

PMID- 15866555
TI  - Impaired prepulse inhibition of acoustic startle in obsessive-compulsive
      disorder.
AB  - BACKGROUND: Animal and clinical studies suggest that impaired sensorimotor
      gating, as assessed with the prepulse inhibition (PPI) paradigm, may result from
      dysfunctional frontostriatal brain circuits and from neurochemical alterations
      which are also implied in the pathophysiology of obsessive-compulsive disorder
      (OCD). However, there is only preliminary evidence about impaired PPI in OCD so
      far. METHODS: Acoustic PPI was measured in 30 OCD patients and 30 matched healthy
      controls with a paradigm using different prepulse intensities. Psychopathology
      assessment included ratings for obsessions, compulsions, and depression. RESULTS:
      PPI was reduced in OCD patients, and this deficit was most pronounced for most
      intense (16 dB(A)) prepulses, where mean PPI was 39.6% in unmedicated patients (n
      = 4), 45.8% in medicated patients, and 58.9% in controls. No group differences
      were observed with regard to the habituation of acoustic startle magnitude.
      Startle measures were generally not associated with clinical measures, although
      such associations may have been obscured by medication effects. CONCLUSIONS: The
      present study confirms deficient central inhibitory functioning in patients with
      OCD and supports the model of deficient frontostriatal circuits in OCD. The
      relationship of PPI deficits to pharmacological and behavioral treatment and to
      possible subtypes of OCD merits further study.

PMID- 15866556
TI  - The prefrontal substrate of reflexive saccade inhibition in humans.
AB  - BACKGROUND: Prefrontal dysfunction in neuropsychiatric disorders such as
      schizophrenia has been shown to impair inhibition of reflexive saccadic eye
      movements; however, it is unclear whether reflexive saccade inhibition can be
      attributed to a distinct subregion of the human prefrontal cortex. METHODS: We
      tested 15 patients with acute unilateral ischemic lesions of the prefrontal
      cortex and 20 control subjects with an antisaccade task. Lesions were
      reconstructed using Talairach coordinates, and possible candidate regions for
      reflexive saccade inhibition were identified. RESULTS: Significantly increased
      antisaccade error rates were observed in patients with lesions affecting a region
      in mid-dorsolateral prefrontal cortex or the white matter between this region and
      the anterior portions of the internal capsule. Antisaccade error rates of
      patients with lesions outside this region were normal. These findings were
      largely independent of lesion volume, postlesion delay, and subject age.
      CONCLUSIONS: Our findings suggest that inhibition of reflexive saccades depends
      on a circumscribed subregion of the human dorsolateral prefrontal cortex. This
      region closely corresponds to Brodmann area 46 as defined by recent
      cytoarchitectonic studies. Increased antisaccade error rates in patients with
      prefrontal pathology may be explained by dysfunction of this region.

PMID- 15866557
TI  - Anxious and hyperactive phenotype following brief ischemic episodes in mice.
AB  - BACKGROUND: Poststroke emotional and behavioral abnormalities have an impact on
      outcome but have scarcely been characterized in animal models. We tested whether
      brief ischemic episodes induce behavioral changes in mice. METHODS: 129/Sv mice
      were subjected to 30-min occlusion of left or right middle cerebral artery (MCAo)
      followed by reperfusion or sham operation (n = 9 or 10 per group). Eight to ten
      weeks later, mice were tested for spontaneous locomotor activity, anxiety in the
      elevated plus maze, and depressive behavior in the modified Porsolt forced swim
      test. Outcome was correlated to monoamine and amino acid levels and compared with
      histologic damage at 10 weeks. RESULTS: Ischemia was associated with increased
      activity (right MCAo) and anxiety (left MCAo), but not poststroke depression.
      Noradrenaline increased by 30%-45% in the ischemic striatum and correlated with
      locomotor activity (r = .48); dopamine and homovanillinic acid were decreased
      compared with sham. The lesion was confined to the striatum, and scattered
      neuronal death was observed in a number of remote brain regions. CONCLUSION:
      Brief ischemic episodes in the mouse induce an anxious, hyperactive but not
      depressive phenotype that may relate to left versus right hemispheric lesion
      location, alterations in brain monoamine levels, and selective neurodegeneration.

PMID- 15866558
TI  - Reinforced spatial alternation as an animal model of obsessive-compulsive
      disorder (OCD): investigation of 5-HT2C and 5-HT1D receptor involvement in OCD
      pathophysiology.
AB  - BACKGROUND: This study introduces a laboratory model of compulsive behavior based
      on persistence in the context of rewarded spatial alternation. METHODS: Rats were
      screened for spontaneous persistence during T-maze reinforced alternation.
      Experiment 1: One high and one low spontaneous persistence group (n = 8) received
      20 injections of fluoxetine, a matched pair saline, both followed by 4 days of
      meta-chlorophenylpiperazine (mCPP) challenge. Experiment 2: Five matched groups
      of rats (n = 9) received pretreatment (20 injections) with fluoxetine, mCPP,
      desipramine, diazepam or saline, followed by 4 days of mCPP challenge (fluoxetine
      in mCPP group). After washout, animals received 2 days of naratriptan, followed
      by another 2-day mCPP challenge. RESULTS: In both experiments mCPP significantly
      increased persistence in saline controls. Fluoxetine also acutely increased
      persistence scores: after a gradual return to baseline, these scores showed
      tolerance to mCPP. Experiment 1: This pattern was significant in high but not low
      initial persistence groups. Experiment 2: Fluoxetine and mCPP showed cross
      tolerance. Neither desipramine nor diazepam protected against mCPP challenge.
      Persistence scores returned to baseline during washout and naratriptan and were
      thereafter increased by another mCPP challenge in all but the fluoxetine and mCPP
      groups, suggesting 5-HT2C receptor mediation. CONCLUSIONS: This model is based on
      spontaneous persistence behavior showing pharmacological responses concordant
      with those of compulsive symptomatology.

PMID- 15866559
TI  - Thyroid hormone alterations among women with posttraumatic stress disorder due to
      childhood sexual abuse.
AB  - BACKGROUND: Research on thyroid activity among male combat veterans with
      posttraumatic stress disorder (PTSD) has consistently shown elevations in total
      triiodothyronine (TT3) and inconsistent elevations of other thyroid variables.
      This study is the first large scale investigation of thyroid function in women
      with PTSD. METHODS: Thyroid function was measured in 63 women with PTSD due to
      childhood sexual abuse (PTSD-CSA) in comparison with a community sample of 42
      women without current PTSD-CSA. Clinical measures included the Clinician
      Administered PTSD Scale (CAPS), the Evaluation of Lifetime Stressors, the Trauma
      Assessment for Adults and the Beck Depression Inventory. RESULTS: Women with PTSD
      CSA showed significant elevations in Total T3 and the TT3/free thyroxine
      (TT3/FT4) ratio, the FT3/TT3 ratio, and modest reductions in thyroid stimulating
      hormone relative to our community sample. These findings could not be explained
      by the influence of prior trauma, lifetime PTSD or depressive symptoms.
      CONCLUSIONS: Altered thyroid activity, especially elevated Total T3 levels, was
      found in women with PTSD associated with childhood sexual abuse.

PMID- 15866560
TI  - Cognitive behavioral therapy guided self-help and orlistat for the treatment of
      binge eating disorder: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Cognitive behavioral therapy (CBT) has efficacy for binge eating
      disorder (BED) but not obesity. No controlled studies have tested whether adding
      obesity medication to CBT facilitates weight loss. We performed a randomized,
      placebo-controlled study of orlistat administered with guided self-help CBT
      (CBTgsh). METHODS: Fifty obese BED patients were randomly assigned to 12-week
      treatments of either orlistat plus CBTgsh (120 mg three times a day [t.i.d.]) or
      placebo plus CBTgsh and were followed in double-blind fashion for 3 months after
      treatment. RESULTS: Seventy-eight percent of patients completed treatments
      without differential dropout between orlistat+CBTgsh and placebo+CBTgsh. Intent
      to-treat remission rates (zero binges for past 28 days on Eating Disorder
      Examination Interview) were significantly higher for orlistat+CBTgsh than
      placebo+CBTgsh (64% versus 36%) at posttreatment but not at 3-month follow-up
      (52% in both). Intent-to-treat rates for achieving 5% weight loss were
      significantly higher for orlistat+CBTgsh than placebo+CBTgsh at posttreatment
      (36% versus 8%) and 3-month follow-up (32% versus 8%). Significant and comparable
      improvements in eating disorder psychopathology and psychological distress
      occurred in both treatments. CONCLUSIONS: The addition of orlistat to CBTgsh was
      associated with greater weight loss than the addition of placebo to CBTgsh.
      Clinical improvements were generally maintained at 3-month follow-up after
      treatment discontinuation.

PMID- 15866561
TI  - Prazosin, an alpha-1 adrenergic antagonist, reduces cocaine-induced reinstatement
      of drug-seeking.
AB  - BACKGROUND: Norepinephrine is implicated in cocaine's behavioral effects. In this
      study, we tested the effect of prazosin, an alpha1-adrenergic receptor
      antagonist, on cocaine-induced reinstatement of drug-seeking behavior. METHODS:
      Rats were trained to self-administer cocaine intravenously under a fixed-ratio 3
      schedule of reinforcement. After behavior was established, cocaine was replaced
      with saline and behavior extinguished. The ability of cocaine (0, 5-20 mg/kg)
      alone or combined with prazosin (.3 mg/kg) to reinstate lever press responding
      was tested. The effects of prazosin on lever press responding for food was
      examined in another set of rats. RESULTS: Cocaine induced a dose-dependent
      reinstatement of drug-seeking behavior that was significantly attenuated by
      prazosin. This dose of prazosin did not alter lever press response rates for
      food. CONCLUSIONS: The attenuation in drug-induced reinstatement is likely not
      due to prazosin-induced suppression of activity. These results suggest alpha1
      adrenergic mechanisms contribute to reinstatement in rats and perhaps, to relapse
      in addicts.

PMID- 15866562
TI  - Social isolation rearing affects prefrontal cortical response to ventral
      tegmental area stimulation.
AB  - BACKGROUND: Animals reared in social isolation exhibit attentional deficits that
      parallel those found in schizophrenia patients. Such disturbances are frequently
      attributed to a dysfunction of the mesocortical system. Here we investigated
      whether electrophysiologic characteristics of prefrontal cortical pyramidal
      neurons or mesocortical responses were changed in isolated animals. METHODS: In
      vivo intracellular recordings were obtained from prefrontal cortical pyramidal
      neurons in animals raised in social isolation or in socialized control animals
      before and after ventral tegmental area stimulation mimicking dopamine cell burst
      firing. RESULTS: Prefrontal cortical pyramidal neurons recorded from isolated
      animals showed bimodal characteristics resembling those of their socialized
      littermates. Stimulation of the ventral tegmental area evoked plateau
      depolarizations in both groups, but this was accompanied by abnormal firing or a
      short hyperpolarization in most of the isolated animals. CONCLUSION: These
      findings suggest that social isolation rearing may affect mesocortical
      information processing.

PMID- 15866563
TI  - Acute yohimbine increases laboratory-measured impulsivity in normal subjects.
AB  - BACKGROUND: State-dependent changes in impulsivity may be related to
      norepinephrine. To examine possible relationships between norepinephrine and
      acute changes in impulsivity, we measured effects of yohimbine, which increases
      norepinephrine release by blocking alpha-2 noradrenergic receptors, on laboratory
      measured impulsivity in healthy subjects without psychiatric or substance-use
      disorders. METHODS: Impulsivity was assessed using the Immediate and Delayed
      Memory Tasks (IMT-DMT), derived from the Continuous Performance Test, before and
      after placebo or two doses of yohimbine, given 4 days apart. Blood pressure was
      monitored, and psychiatric symptoms were measured using self-rated visual analog
      scales. RESULTS: Yohimbine was associated with a dose-related increase in
      impulsive IMT commission errors, with an increase of > 50% relative to baseline
      at the higher dose. The activation factor of the Internal State Scale was
      increased at the same dose. CONCLUSIONS: These results are consistent with
      increased impulsivity in normal subjects given yohimbine, possibly related to
      increased norepinephrine.

PMID- 15866564
TI  - An update: spontaneous premature ovarian failure is not an early menopause.
AB  - OBJECTIVE: To update clinicians regarding the management of women with
      spontaneous premature ovarian failure (POF). DESIGN: Literature review and
      consensus building among three clinicians with experience in caring for women
      with spontaneous POF. CONCLUSION(S): Clearly the ovarian "failure" in this
      disorder is not permanent in all women. Approximately 5%-10% may conceive
      spontaneously and unexpectedly after the diagnosis. An integrated approach to
      management is best, and there is a need to first address physical and mental
      health issues before addressing plans for family building. Women with spontaneous
      POF are at increased risk of adrenal insufficiency, which should be detected and
      managed appropriately, especially before proceeding to ovum or embryo donation
      procedures. Young women with POF experience pathologically low serum E2 levels at
      least intermittently. Despite the absence of controlled evidence for this
      specific population, physiologic replacement of ovarian steroid hormones seems
      rational until the age of normal menopause. The disorder may be associated with
      other conditions that require evaluation and management, including
      hypothyroidism, dry eye syndrome, abnormal karyotype, or a premutation of the
      FMR1 gene. Finally, clinicians need to be sensitive to the emotional aspects of
      this disorder when delivering the diagnosis and during subsequent management.

PMID- 15866565
TI  - Acute depletion of murine primordial follicle reserve by gonadotropin-releasing
      hormone antagonists.
AB  - OBJECTIVE: To examine the effects of GnRH antagonists on preantral follicle
      survival in vivo and to investigate whether GnRH antagonist use during
      cyclophosphamide treatment would protect the ovary and preserve primordial
      follicle survival in a murine model. DESIGN: Prospective basic research study.
      SETTING: Research laboratory in an academic medical center. ANIMAL(S): Adult
      C57Bl/6 mice (5 to 6 weeks old). INTERVENTION(S): Mice received either a single
      injection of GnRH agonist (leuprolide acetate) on study day -10 or injections of
      the GnRH antagonist (antide or cetrorelix) on study days -3 and 0. Some animals
      also received the chemotherapeutic agent cyclophosphamide on day 0. All animals
      were killed by CO2 asphyxiation on day 7. To examine direct vs. indirect effects,
      some mice received GnRH antagonist under the bursa of one ovary, with the
      contralateral ovary receiving vehicle. Ovaries were fixed in Kahle's solution; 7
      mum tissue sections were stained with Lillie's allochrome, and preantral
      follicles were counted on every fifth section. MAIN OUTCOME MEASURE(S): Numbers
      of primordial, primary, and secondary follicles. RESULT(S): Systemic
      administration of both GnRH antagonists caused a significant destruction of
      primordial follicles compared with control mice. Similar results were obtained
      whether the antagonists were administered systemically or directly to the ovary.
      Gonadotropin-releasing hormone agonist had no effect on primordial follicle
      numbers by itself but reduced the follicular depletion caused by
      cyclophosphamide. CONCLUSION(S): In contrast to the effects of GnRH agonists to
      reduce chemotherapeutic destruction of primordial follicles, GnRH antagonists do
      not protect the ovary from the damaging effects of cyclophosphamide. More
      importantly, GnRH antagonists alone deplete primordial follicles in this murine
      model, likely through a direct effect on the ovary. Whether these observations
      apply to other species requires further study.

PMID- 15866566
TI  - Gonadotropin-releasing hormone (GnRH) analogues and the ovary: do GnRH
      antagonists destroy primordial follicles?
AB  - The study by Danforth et al. shows that gonadotropin-releasing hormone (GnRH)
      antagonists do not protect ovarian follicles from chemotherapy-induced damage and
      that GnRH antagonists alone reduce primordial follicle numbers in mice. This
      article discusses the strengths and limitations of the study by Danforth et al.,
      as well as the potential mechanism of action of GnRH antagonists according to the
      literature.

PMID- 15866567
TI  - Diagnostic criteria for polycystic ovary syndrome: a reappraisal.
AB  - New diagnostic criteria for polycystic ovary syndrome (PCOS) were proposed in
      Rotterdam in 2003, which expanded the previous definition that arose from an
      expert conference sponsored by the National Institutes of Health (NIH) in 1990.
      However, these newer criteria give rise to phenotypes that may not actually
      represent PCOS, and a simple modification of the 1990 NIH/National Institute of
      Child Health and Human Disease diagnostic criteria may be more consistent with
      currently available data.

PMID- 15866568
TI  - Preimplantation genetic diagnosis: technological promise and ethical perils.
AB  - OBJECTIVE: To describe the ethical issues inherent to the current and foreseeable
      uses of preimplantation genetic diagnosis (PGD). DESIGN: Review of ethical
      principles and their application to PGD. SETTING: Academic medical center.
      PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A discussion of
      the current ethical perils surrounding the use of PGD, and a prediction of future
      ethical quandaries that will arise from the use of this technology. RESULT(S):
      Although PGD may be used to predict and prevent disease, it may also be used to
      determine nondisease traits. The ever-expanding ability of genetics to determine
      qualities of the preimplantation embryo continues to open up new ethical
      questions relating to the use of PGD for preimplantation diagnosis.
      CONCLUSION(S): Preimplantation genetic diagnosis is a powerful technique with
      many positive applications. As with all such new technologies, care should be
      taken to ponder the ethical implications of its use before routinely accepting
      PGD as a tool in the reproductive armamentarium.

PMID- 15866569
TI  - A prospective randomized study comparing gonadotropin-releasing hormone agonists
      or gonadotropin-releasing hormone antagonists in couples with unexplained
      infertility and/or mild oligozoospermia.
AB  - OBJECTIVE: To compare the efficacy of GnRH antagonist vs. GnRH agonist
      administration for controlled ovarian hyperstimulation (COH) in assisted
      reproduction. DESIGN: A prospective, randomized trial. SETTING: Clinical research
      unit at a tertiary care medical center. PATIENT(S): Sixty-five patients with
      unexplained infertility or mild male subfertility undergoing COH for IUI.
      INTERVENTION(S): Twenty-nine women (group A) were randomized to receive 600
      microg of busereline acetate per day starting in the midluteal phase of the cycle
      (long protocol), whereas 36 women (group B) were treated with 0.25 mg/d of the
      GnRH antagonist Cetrorelix starting from day 6 of the cycle. The starting dose of
      recombinant FSH was 150 IU in women of both groups. Insemination was performed 34
      hours after hCG injection. MAIN OUTCOME MEASURE(S): Clinical and successful
      ongoing pregnancy rate (PR), measurements of serum FSH, LH, E2, and P, number of
      recruited follicles, duration of stimulation period, and amount of gonadotropins
      used. RESULT(S): Women in group A required significantly more days of treatment
      (median: 12.0 vs. 9.0) and significantly more total units of recombinant FSH
      (median 1,800 vs. 1,550) as compared with the corresponding values of the
      antagonist group (group B). Serum FSH, LH, E2, and P were significantly higher on
      the antagonist group on days 2 and 6 of stimulation. However, these differences
      regress until the day of hCG administration. CONCLUSION(S): The GnRH antagonists
      have facilitated short and simple treatment, and are particularly attractive for
      administration in women undergoing COH, achieving comparable PR with the long
      protocol regimen.

PMID- 15866570
TI  - Characterization and mutation analysis of the human formin-2 (FMN2) gene in women
      with unexplained infertility.
AB  - OBJECTIVE: Formin-2 (Fmn2) mutant mice produce oocytes with meiosis I arrest. Our
      aim was to describe the human FORMIN-2 (FMN2) gene and to identify DNA sequence
      polymorphisms in patients with unexplained infertility and multiple failed IVF
      cycles. DESIGN: Institutional review board-approved observational case-control
      study. SETTING: Infertility center and university hospital. PATIENT(S): Sixty-two
      fertile controls and seven subjects with unexplained infertility.
      INTERVENTION(S): BLASTP (www.ncbi.nlm.nih.gov) was used to map the genomic DNA
      and complementary DNA sequence of FMN2. Genomic DNA was extracted from blood
      leukocyte samples. The polymerase chain reaction was used to amplify FMN2 gene
      exons for analysis by denaturing gradient gel electrophoresis. MAIN OUTCOME
      MEASURE(S): Characterization of the FMN2 gene and identification of fragment
      melting polymorphisms (FMPs). RESULT(S): FMN2 includes 411,960 base pairs (bp) of
      DNA with 6,204 bp in 18 exons. There was no difference in FMN2 FMP allele
      frequencies between the controls and subjects. One patient was homozygous for one
      FMP. CONCLUSION(S): The human FMN2 gene is conserved between evolutionarily
      diverse vertebrates. It is likely that FMN2 has the same function as Fmn2 in the
      mouse (i.e., maintenance of the meiotic spindle). Prospective identification of
      patients with meiosis I arrest is necessary to determine whether FMN2 mutations
      are a cause of unexplained infertility.

PMID- 15866571
TI  - Optimization of estradiol supplementation during the luteal phase improves the
      pregnancy rate in women undergoing in vitro fertilization-embryo transfer cycles.
AB  - OBJECTIVE: To evaluate the influence of different E2 supplementation doses during
      the luteal phase on implantation and pregnancy rates in women undergoing
      intracytoplasmic sperm injection (ICSI) cycles. DESIGN: Prospective, randomized
      study. SETTING: A private IVF unit. PATIENT(S): One hundred sixty-six women
      younger than 40 years who were undergoing IVF with long protocol controlled
      ovarian hyperstimulation (COH). A total of 231 cycles were investigated. Group 1
      (P only) included 80 cycles, group 2 (P and 2 mg of E2) included 73 cycles, and
      group 3 (P and 6 mg of E2) included 78 cycles. INTERVENTION(S): Supplementation
      in the luteal phase with different doses of E2 (0, 2, or 6 mg/d). MAIN OUTCOME
      MEASURE(S): Serum E2 and P levels in the late luteal phase, and implantation rate
      and pregnancy rate (PR) were documented. The data were analyzed with regard to
      the entire study population and further stratified according to the E2 dose used.
      RESULT(S): Significantly higher implantation rate and PR were recorded in those
      who received low dose E2 supplementation compared with no substitution (PR 23.1%
      vs. 32.8%). The best implantation and pregnancy results were found significantly
      in the group with high dose E2 supplementation (PR 51.3%). CONCLUSION(S): For
      women treated with a long GnRH analogue protocol for COH, addition of a high dose
      of E2 to daily P supplementation significantly improved the IVF-embryo transfer
      results.

PMID- 15866572
TI  - Diminished intrafollicular estradiol levels in in vitro fertilization cycles from
      women with reduced ovarian response to recombinant human follicle-stimulating
      hormone.
AB  - OBJECTIVE: To correlate serum and intrafollicular E(2) levels in women receiving
      GnRH agonist and recombinant human (h)FSH for IVF. DESIGN: Prospective study.
      SETTING: Academic IVF center. PATIENT(S): Twenty-three nonhirsute ovulatory
      women. INTERVENTION(S): In vitro fertilization cycles were classified as high- or
      low-normal response, according to whether the amount of recombinant hFSH
      administered was below or above, respectively, the mean recombinant hFSH given to
      all women combined. Serum bioactive LH and immunoreactive FSH were measured
      during pituitary desensitization preceding recombinant hFSH and repeated at
      oocyte retrieval. The first mature follicle aspirated from either ovary had a
      mean diameter >15 mm. MAIN OUTCOME MEASURE(S): Serum and follicular fluid (FF)
      insulin, bioactive LH, immunoreactive FSH, and steroid levels. RESULT(S): Basal
      serum gonadotropin levels were comparable between female groups. Serum
      immunoreactive FSH levels, but not bioactive LH levels, at oocyte retrieval were
      greater in cycles of low-normal vs. high-normal response, whereas maximum serum
      E2 levels and total oocyte counts were similar between both groups. Despite
      elevated FF immunoreactive FSH levels, FF E2 was decreased in low-normal response
      cycles. Intrafollicular T and P also were decreased and increased, respectively,
      in cycles of low-normal response, although FF bioactive LH levels were comparable
      in both groups. CONCLUSION(S): Intrafollicular E2 is decreased in cycles of
      reduced ovarian responsiveness to GnRH agonist and recombinant hFSH and is not
      predicted by maximal serum E2 or number of oocytes retrieved.

PMID- 15866573
TI  - An initial low response predicts poor outcome in in vitro
      fertilization/intracytoplasmic sperm injection despite improved ovarian response
      in consecutive cycles.
AB  - OBJECTIVE: To study the predictive value of initial low response (LR) in
      IVF/intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective analysis.
      SETTING: Two Finnish fertility centers. PATIENT(S): A total of 3,846 IVF/ICSI
      cycles performed from 1994 to 2002. INTERVENTION(S): Consecutive cycles in the
      same subject were identified. The study groups consisted of subjects who had
      three treatment cycles and at least one LR cycle (n = 80). MAIN OUTCOME
      MEASURE(S): Pregnancy rate (PR), total gonadotropin dose, and embryo quality.
      RESULT(S): Only 2.5% (2/80) of subjects had a LR in all three consecutive cycles.
      In 43 women an initial LR was followed by >/=1 normal response (NR) cycle, and in
      35 women an initial NR was followed by >/=1 LR cycle. The PR/cycle was similarly
      low in women with an initial LR and an initial NR (10.1% vs. 16.2%). An increase
      in gonadotropin dose resulted in a higher number of oocytes in women with an
      initial LR (from 2.1 +/- 0.9 to 6.7 +/- 2.7) but the PR/cycle remained low,
      compared to the overall mean PR (27.2%). In cycles in which top quality embryos
      were transferred, subjects with an initial LR had a lower PR than women with an
      initial NR (17.8% vs. 41.2%). CONCLUSION(S): An initial LR is a predictor of poor
      outcome in subsequent cycles, even if ovarian response is improved by increasing
      the gonadotropin dose or a top quality embryo is replaced.

PMID- 15866574
TI  - Greater implantation and pregnancy rates with vaginal progesterone in
      intracytoplasmic sperm injection but not in in vitro fertilization cycles: a
      retrospective study.
AB  - OBJECTIVE: To compare the effectiveness of vaginal progesterone supplementation
      with intramuscular supplementation in assisted reproduction cycles. DESIGN:
      Retrospective study. SETTING: Physiopathology of Human Reproduction Unit,
      Pordenone, Italy, from July 2000 to June 2004. PATIENT(S): Three hundred and
      eight-five intracytoplasmic sperm injection (ICSI) procedures (188 with vaginal
      gel and 197 with intramuscular progesterone) and 373 in vitro fertilization (IVF)
      cycles (227 with vaginal and 146 with intramuscular progesterone).
      INTERVENTION(S): Progesterone luteal supplementation: vaginal gel (Crinone 8% 90
      mg/day) or intramuscular (Prontogest 50 mg/day). MAIN OUTCOME MEASURE(S):
      Implantation rates, and total and clinical pregnancy rates. RESULT(S): Higher
      rates of implantation and total and clinical pregnancies were observed in the
      vaginal supplemented ICSI subgroup than in the intramuscular one. This difference
      was observed for all transfers (13.3% vs. 8.8%, 39.8% vs. 23.3%, and 28.7% vs.
      18.6%) and for ultrasound-guided transfers (17.2% vs. 9.3%, 49% vs. 27%, and
      36.9% vs. 21.1%, respectively). CONCLUSION(S): The vaginal route of luteal
      supplementation may be better than the intramuscular one, yielding higher
      implantation rates as well as total and clinical pregnancy rates in ICSI cycles
      but not in classic IVF treatments.

PMID- 15866575
TI  - Blastocyst formation in in vitro fertilization versus intracytoplasmic sperm
      injection cycles: influence of the fertilization procedure.
AB  - OBJECTIVE: To compare the quality of early cleaving embryos and blastocysts
      obtained by IVF or intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective
      study. SETTING: Tertiary infertility center. PATIENT(S): Sibling oocytes of 104
      patients in 104 IVF vs. ICSI cycles. INTERVENTION(S): Cumulus oocyte complexes (n
      = 1,358) were randomly subjected to ICSI or IVF. MAIN OUTCOME MEASURE(S): Embryo
      development and blastocyst formation rate. The blastocyst quality and cycle
      efficiency were also evaluated. RESULT(S): Early embryo cleavage was higher after
      ICSI (37.1%) compared to IVF (14.1%). The percentage of > or =4-cell embryos on
      day 2 and > or =8-cell embryos on day 3 was similar for both procedures. The
      overall blastocyst formation was not different between ICSI (50.2%) and IVF
      (54.8%), neither was the percentage of good-quality blastocysts (31.3% for ICSI
      and 36.0% for IVF). The total cycle efficiency (percentage of embryos transferred
      and frozen per two pronuclei [2PN]) was comparable for the two techniques (51.7%
      for ICSI and 57.4% for IVF). CONCLUSION(S): No differences were found on sibling
      oocytes in the embryo development and blastocyst formation, irrespective of the
      fertilization procedure. Earlier suggestions that the ICSI technique may result
      in impaired blastocyst development were not confirmed in this study.

PMID- 15866576
TI  - The singleton, term gestation, and live birth rate per cycle initiated: a 1-year
      experience in in vitro fertilization cycles with native and donated oocytes.
AB  - OBJECTIVE: To investigate the singleton, term gestation, and live birth rate per
      cycle initiated in our IVF program during a 1-year period. DESIGN: Retrospective
      study of all first IVF cycles performed in the year 2002, with or without
      intracytoplasmic sperm injection (ICSI), with day 2/3 embryo transfer and using
      native or donated oocytes. SETTING: Instituto Valenciano de Infetilidad (IVI),
      Valencia, Spain. PATIENT(S): Of 3,158 IVF cycles initially considered, 165 were
      excluded because of embryo freezing, follow-up loss, or embryo reduction. Of the
      remaining cycles, only 1,836 were first cycles with day 2/3 embryo transfer; of
      these, native oocytes were employed in 1,095 and donated oocytes in 741.
      INTERVENTION(S): No patient underwent any additional procedure or intervention.
      MAIN OUTCOME MEASURE(S): The singleton, term gestation, and live birth rate per
      cycle initiated was used as a primary outcome measure. Results were analyzed
      according to the origin of the oocytes (native vs. donated) and the woman's age
      (<37 and > or =37 years old). RESULT(S): The ectopic pregnancy rate was higher in
      the native oocyte group. The singleton, term gestation, and live birth rate per
      cycle initiated was similar in native and donated oocyte groups (15.3% vs.
      13.4%). In the native oocyte group, patients <37 years old showed a significantly
      better outcome. The singleton, term gestation, and live birth rate per cycle
      initiated was 16.7% and 10.8% in younger and older women, respectively.
      CONCLUSION(S): The singleton, term gestation, and live birth rate per cycle
      initiated constitutes an essential parameter for determining the real possibility
      of a healthy baby for a specific assisted reproduction technology (ART).

PMID- 15866577
TI  - Soluble human leukocyte antigen G expression in phase I culture media at 46 hours
      after fertilization predicts pregnancy and implantation from day 3 embryo
      transfer.
AB  - OBJECTIVE: To compare pregnancy and implantation rates after ART when embryos for
      day 3 embryo transfer were selected based on soluble HLA-G (sHLA-G) expression in
      the culture media at 46 hours after fertilization by intracytoplasmic sperm
      injection (ICSI). DESIGN: Prospective cohort study. SETTING: Private practice.
      PATIENT(S): One hundred seven patients undergoing ART aged <39 years with normal
      ovarian reserve, a normal uterine cavity, and two or more embryos scoring > or
      =70 by the graduated embryo scoring (GES) method, transferred on day 3.
      INTERVENTION(S): Patients were divided into two groups. In group A (n = 51) all
      embryos transferred expressed sHLA-G above the geometric mean (sHLA-G+), whereas
      in group B (n = 56) all embryos transferred were sHLA-G-ve. MAIN OUTCOME
      MEASURE(S): Viable pregnancy rate (patients with fetal heart activity at 8 weeks
      of gestation per embryo transfer procedure), and implantation rate (viable
      gestational sacs per total embryos transferred). RESULT(S): When all embryos
      transferred were sHLA-G+ve the pregnancy and implantation rates were 75% (38/51)
      and 44% (51/116), respectively, compared to 23% (13/56) and 14% (20/143) when all
      embryos transferred were sHLA-G-ve. CONCLUSION(S): Pregnancy and implantation
      rates after day 3 embryo transfer are improved when sHLA-G expression in phase I
      culture media at 46 hours after fertilization by ICSI is used prospectively as a
      criterion for selecting optimal embryos for transfer.

PMID- 15866578
TI  - Serum CA-125 levels in the second week after embryo transfer predict clinical
      pregnancy.
AB  - OBJECTIVE: To correlate CA-125 concentrations in serum samples collected for
      routine hCG measurements 11 +/- 2 days after embryo transfer in relation to
      pregnancy and its outcome. DESIGN: Retrospective study. SETTING: University-based
      in vitro fertilization (IVF) program. PATIENT(S): One hundred and eighty-two
      consecutive pregnancies conceived after IVF or intracytoplasmic sperm injection,
      and 41 control cycles without pregnancy from the same patients. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Analysis of correlation between CA-125
      concentrations and hCG and inhibin A levels. Predictive accuracy of these markers
      was compared by receiver-operating characteristic (ROC) analysis. RESULT(S): The
      CA-125 levels were statistically significantly higher in pregnant than in
      nonpregnant patients. Within pregnant cycles, CA-125 concentrations correlated
      positively with levels of hCG and inhibin A. The CA-125 levels were statistically
      significantly lower in preclinical abortions than in clinical pregnancies. No
      statistically significant difference was observed between early pregnancy losses
      and ongoing pregnancies or singleton and multiple pregnancies, respectively. The
      predictive accuracy of CA-125 measurements was statistically significantly lower
      than that achieved with hCG or inhibin A. CONCLUSION(S): Although CA-125 levels
      seem to be predictive of clinical pregnancy, they are not predictive of its
      outcome. Higher CA-125 concentrations may reflect higher endometrial receptivity
      but do not predict the number or viability of implanted embryos.

PMID- 15866579
TI  - Psychosocial risks associated with multiple births resulting from assisted
      reproduction.
AB  - OBJECTIVE: To determine if increased psychosocial risks are associated with each
      increase in birth multiplicity (i.e., singleton, twin, triplet) resulting from
      assisted reproduction. DESIGN: Stratified random sample (n = 249). SETTING: An
      academic teaching hospital and private practice infertility center. PATIENT(S):
      Mothers raising 1- to 4-year-old children (n = 128 singletons, n = 111 twins, and
      n = 10 triplets) conceived through assisted reproduction. INTERVENTION(S): Self
      administered, mailed survey. MAIN OUTCOME MEASURE(S): Scales measuring material
      needs, quality of life, social stigma, depression, stress, and marital
      satisfaction. RESULT(S): Using multivariate logistic regression models, for each
      additional multiple birth child, the odds of having difficulty meeting basic
      material needs more than tripled and the odds of lower quality of life and
      increased social stigma more than doubled. Each increase in multiplicity was also
      associated with increased risks of maternal depression. CONCLUSION(S): To
      increase patients' informed decision-making, assisted reproduction providers
      might consider incorporating a discussion of these risks with all patients before
      they begin fertility treatment, and holding the discussion again if the treatment
      results in a multiple gestation. These data may also help providers to identify
      appropriate counseling, depression screening, and supports for patients with
      multiple births.

PMID- 15866580
TI  - Effects of competition among fertility centers on pregnancy and high-order
      multiple gestation rates.
AB  - OBJECTIVE: To measure the effect of competition among fertility centers on
      pregnancy and high-order multiple (HOM) gestation rates after IVF. DESIGN:
      Retrospective cohort study. SETTING: Four hundred eight fertility clinics
      registered with the Society for Assisted Reproductive Technology as providing IVF
      services in 2000. Competition was defined as number of clinics in a
      geographically defined area. Demand for services was based on the population of
      reproductive-aged women. PATIENT(S): Three hundred eighty-one fertility clinics
      reporting clinical outcomes. INTERVENTION(S): Pregnancy rates, HOM gestation
      rates, population of reproductive-aged women, and number of competing clinics
      were calculated for each clinic from Society for Assisted Reproductive Technology
      and census data. MAIN OUTCOME MEASURE(S): The clinic HOM gestation rate
      (percentage of pregnancies that were HOM) and age-adjusted pregnancy rate.
      RESULT(S): The number of clinics in an area of competition ranged from 1 to 22.
      The HOM gestation rate per clinic ranged from 0% to 50%. As demand increased,
      competition increased. As competition increased, the number of HOM pregnancies
      per clinic decreased. In areas of low competition (1 to 2 clinics) the clinic HOM
      gestation rate was 8.43%, in areas of intermediate competition (3-7 clinics)
      8.39%, and in areas of high competition (8-22 clinics) 8.24%. In areas with
      intermediate demand, high levels of competition resulted in fewer HOM pregnancies
      than intermediate competition (relative risk 0.56, 95% confidence interval 0.36
      0.89) or low levels of competition (RR 0.57, 95% confidence interval 0.35-0.94).
      Age-adjusted pregnancy rates did not differ by level of competition.
      CONCLUSION(S): According to these data, the risk of HOM gestation decreases with
      increasing competition among clinics; however, pregnancy rates are unaffected.

PMID- 15866581
TI  - Delayed vasectomy success in men with a first postvasectomy semen analysis
      showing motile sperm.
AB  - OBJECTIVE: To determine the frequency of and factors associated with delayed
      vasectomy success in men with first postvasectomy semen analysis showing motile
      sperm. DESIGN: Descriptive study. SETTING: One hospital-based family planning
      clinic and two private clinics from the Quebec City area, Canada. PATIENT(S):
      Three hundred nine men vasectomized between 1990 and 2001 and who had a first
      semen analysis showing motile sperm. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Vasectomy success, based on the last available semen analysis-either
      in the medical record or as requested for the study-and on sterility as
      established by a telephone-based questionnaire in 2003. RESULT(S): Among the 309
      men, 174 (56.3%, 95% confidence interval 50.7%-61.7%) had delayed vasectomy
      success. Significant independent factors associated with delayed vasectomy
      success were lower sperm count in the first postvasectomy semen analysis and
      shorter interval between vasectomy and first postvasectomy semen analysis.
      CONCLUSION(S): Delayed vasectomy success occurs in more than half of men with a
      first postvasectomy semen analysis showing motile sperm. The decision to repeat
      vasectomy should not rely on a single semen analysis showing motile sperm.

PMID- 15866582
TI  - Effects of magnetic-activated cell sorting on sperm motility and cryosurvival
      rates.
AB  - OBJECTIVE: To evaluate the effect of magnetic-activated cell sorting in
      cryopreservation-thawing protocols on sperm motility and cryosurvival rate.
      DESIGN: Prospective-controlled study. SETTING: Andrology department at a
      university-based medical institution. PATIENT(S): Ten healthy volunteer sperm
      donors. INTERVENTION(S): Sperm populations were separated using annexin-V
      magnetic-activated cell sorting before and after the cryopreservation-thawing
      process. MAIN OUTCOME MEASURE(S): Sperm motility and cryosurvival rate.
      RESULT(S): Annexin-negative sperm separated by magnetic-activated cell sorting
      had statistically significantly higher motility following cryopreservation
      thawing than sperm that were not separated. Similarly, annexin-negative
      spermatozoa also had higher cryosurvival rate than sperm cryopreserved without
      magnetic-activated cell sorting and sperm that were annexin-positive.
      CONCLUSION(S): Superparamagnetic annexin V-conjugated microbeads can separate
      spermatozoa with externalized phosphatidylserine, which is considered one of the
      early features of late apoptosis. The separation of a distinctive population of
      nonapoptotic spermatozoa with intact membranes may optimize the cryopreservation
      thawing outcome. Magnetic-activated cell sorting using annexin-V microbeads
      enhances sperm motility and cryosurvival rates following cryopreservation.

PMID- 15866583
TI  - Phenotypic characterization of the immune and mast cell infiltrates in the human
      testis shows normal and abnormal spermatogenesis.
AB  - OBJECTIVE: To assess the types, distributions, and numbers of immune cell
      infiltrates in the testes of men with azoospermia. DESIGN: Prospective study.
      SETTING: University research and clinical institutes. PATIENT(S): Thirty-one men
      with azoospermia showing normal spermatogenesis (n = 10), germ cell maturation
      arrest (GA, n = 12), and Sertoli cell-only syndrome (SCO, n = 9).
      INTERVENTION(S): Testicular tissue biopsies. Sections were stained with routine
      (hematoxyline and eosin), special (Masson Trichrome, Gordon, Periodic Acid
      Schiff, Aldehyde Fuchsin, and Orcein stains), and immunoperoxidase stains (using
      monoclonal antibodies for B and T cells and CD68 macrophages). MAIN OUTCOME
      MEASURE(S): Serum levels of T, FSH, and LH in addition to histopathological
      analysis. RESULT(S): Hormonal profiles were unremarkable in all patients. Marked
      deposition of the reticular and collagen fibers was seen more in abnormal than
      normal spermatogenesis. The immune (B and T lymphocytes and CD68 macrophages) and
      mast cells were found in the interstitium, tubular walls, and lumens of all the
      testes analyzed. The differential counts of these cells (B and T lymphocytes,
      CD68 macrophages, and mast cells, respectively) were higher in SCO (1.66 +/-
      0.46, 9.14 +/- 1.30, 2.26 +/- 1.68, 3.35 +/- 0.23) and GA (2.03 +/- 0.48, 4.70 +/
      1.00, 2.61 +/- 0.70, and 4.18 +/- 0.13) when compared with those in normal
      spermatogenesis (1.22 +/- 0.19, 5.41 +/- 0.58, 1.55 +/- 0.33, and 2.26 +/- 0.13).
      Increased cellular counts were not statistically significant for T and B cells
      and macrophages. However, these differences were statistically significant for
      mast cells. CONCLUSION(S): Abnormal spermatogenesis is associated with increased
      numbers of the immune and mast cells. Our findings may reflect an exaggerated
      immune response in these cases.

PMID- 15866584
TI  - Prevalence of insulin resistance in the polycystic ovary syndrome using the
      homeostasis model assessment.
AB  - OBJECTIVE: To determine the prevalence of insulin resistance (IR) in a large
      population of patients with the polycystic ovary syndrome (PCOS). DESIGN:
      Prospective, case-control. SETTING: University medical center. PATIENT(S): Two
      hundred seventy-one PCOS patients and 260 eumenorrheic, non-hirsute, control
      women. INTERVENTION(S): History and physical examination and blood sampling. MAIN
      OUTCOME MEASURE(S): Total T, free T, DHEAS, sex hormone-binding globulin, and
      fasting glucose and insulin levels; homeostatic model assessment values for IR
      (HOMA-IR) and percent beta-cell function (HOMA-%beta-cell). RESULT(S): Patients
      with PCOS and controls differed significantly in all parameters studied, except
      fasting glucose. Because the HOMA-IR and HOMA-%beta-cell values were variably
      associated with race, age, and body mass index, the HOMA-IR and HOMA-%beta-cell
      values were then adjusted for these cofounders. After adjustment, 64.4% of PCOS
      patients were noted to be insulin resistant, and 2.6% had beta-cell dysfunction.
      Compared with PCOS patients without IR (n = 96), patients with IR (n = 174) were
      more obese and had higher beta-cell function. CONCLUSION(S): In patients with
      PCOS, the prevalence of IR was 64% according to the HOMA-IR measurement, after
      adjustment. Patients with IR were more clinically affected. Although IR is a
      common abnormality in PCOS, it does not seem to be a universal feature.

PMID- 15866585
TI  - Obstetric outcome of patients with polycystic ovary syndrome treated by in vitro
      maturation and in vitro fertilization-embryo transfer.
AB  - OBJECTIVE: To assess the obstetric outcome of pregnancies resulting from in vitro
      maturation (IVM) and IVF-ET of immature oocytes retrieved from women with
      polycystic ovary syndrome (PCOS). DESIGN: Prospective observational study.
      SETTING: University fertility clinic. PATIENT(S): One hundred thirty-nine women
      undergoing 203 IVM treatment cycles. INTERVENTION(S): Immature oocyte recovery
      from unstimulated ovaries. In vitro oocyte maturation and fertilization. Fresh ET
      and assessment of obstetric outcomes in the pregnant women. MAIN OUTCOME
      MEASURE(S): Pregnancy and obstetric outcome. RESULT(S): Forty-one pregnancies
      were obtained in 187 ETs, resulting in a pregnancy rate of 21.9%. Except for
      three patients lost to follow-up in these pregnancies, the abortion and live
      birth rates were 36.8% (14 of 38) and 63.2% (24 of 38), respectively. The mean
      (+/-SD) gestational age and birth weight at delivery for singletons were 38.4 +/-
      2.0 weeks (range, 33-41.6 weeks) and 3,252 +/- 516 g (1,750-4,100 g),
      respectively. For twins these were 36.7 +/- 1.9 weeks (34.6-39 weeks) and 2,361
      +/- 304 g (1,900-2,990 g), respectively. Pregnancy complications occurred in five
      patients (13.2%); these included preterm labor (n = 3) and placenta previa (n =
      2). Two patients (5.3%) had a major congenital anomaly diagnosed by
      ultrasonography. CONCLUSION(S): The abortion rate, gestational age and birth
      weight at delivery, and obstetric complications of pregnancies conceived by IVM
      ET in women with PCOS were comparable with those of other women with PCOS being
      treated by conventional IVF-ET. In vitro maturation followed by IVF-ET seems to
      be a useful treatment option for women with PCOS, thus avoiding the risk of
      ovarian hyperstimulation syndrome.

PMID- 15866586
TI  - Subcutaneous administration of pulsatile gonadotropin-releasing hormone decreases
      serum follicle-stimulating hormone and luteinizing hormone levels in women with
      polycystic ovary syndrome: a preliminary study.
AB  - OBJECTIVE: The main objectives of this study were to investigate whether [1]
      subcutaneous (SC) administration of pulsatile gonadotropin-releasing hormone
      (GnRH) decreases the increased levels of luteinizing hormone (LH) observed in
      women with polycystic ovary syndrome (PCOS); and [2] GnRH administration modifies
      the pattern of LH secretion observed in these patients. DESIGN: Serum follicle
      stimulating hormone (FSH) and LH levels and LH pulse amplitude and pulse interval
      were determined in 13 patients with PCOS during the first 3 days of the cycle
      following the administration of 10 mg of medroxyprogesterone acetate during 5
      days. SETTING: Infertility clinic. PATIENT(S): Thirteen women with PCOS.
      INTERVENTION(S): Determination of FSH and LH serum levels after SC administration
      of pulsatile GnRH. MAIN OUTCOME MEASURE(S): The FSH and LH levels in serum.
      RESULT(S): Mean FSH and LH levels in serum decreased following the administration
      of subcutaneous pulsatile GnRH in all treated women compared with baseline
      values. The LH pulse amplitude and pulse interval decreased in all patients
      following the administration of pulsatile GnRH. CONCLUSION(S): The SC
      administration of pulsatile GnRH in women with PCOS significantly decreases FSH
      and LH levels in serum. A decrease in the secretion of gonadotropins, without
      reaching the intense suppression observed with GnRH analogues, could be of great
      utility in in vitro fertilization (IVF) treatments.

PMID- 15866587
TI  - Effect of myomectomy on the outcome of assisted reproductive technologies.
AB  - OBJECTIVE: To evaluate the impact of myomectomy on in vitro fertilization-embryo
      transfer (IVF-ET) and oocyte donation cycle outcome. DESIGN: Retrospective case
      controlled study of consecutive fresh IVF-ET and oocyte donation patients during
      a 2-year interval. SETTING: Private assisted reproductive technology (ART)
      center. PATIENT(S): Patients with submucosal leiomyomata resected
      hysteroscopically (group A: 15 oocyte donor recipients; group 1 = 31 IVF-ET
      patients) and those with intramural components or strictly intramural leiomyomata
      that distorted or impinged upon the endometrial cavity resected at laparotomy
      (group B = 26 oocyte donor recipients; group 2 = 29 IVF-ET patients).
      INTERVENTION(S): Precycle hysteroscopic or abdominal myomectomy and subsequent
      fresh IVF-ET or oocyte donation. MAIN OUTCOME MEASURE(S): Results of controlled
      ovarian hyperstimulation as well as ongoing pregnancy and implantation rates were
      evaluated in comparison with contemporaneous patient groups without such lesions
      (group C = 552 oocyte donor recipients; group 3: 896 IVF-ET patients). RESULT(S):
      As would be expected, the mean number and size of leiomyomata were significantly
      larger in patients who underwent abdominal myomectomy. However, neither ongoing
      pregnancy nor implantation rates were significantly different in comparison with
      controls among either oocyte donor recipients (group A: 86.7%, 57.8%; group B:
      84.6%, 55.2%; group C 77%, 49.1%). The findings were similar for those undergoing
      IVF-ET in comparison with controls (group 1: 61%, 24%; group 2: 52%, 26%; group
      3: 53%, 23%). CONCLUSION(S): Precycle resection of appropriately selected
      clinically significant leiomyomata results in IVF-ET or oocyte donation cycle
      outcomes that are similar to controls.

PMID- 15866588
TI  - Serum levels of soluble vascular cell adhesion molecule-1 are decreased in women
      receiving oral contraceptives compared with normally menstruating women:
      implications in atherosclerosis.
AB  - OBJECTIVE: The primary objective was to assess whether short-term changes in
      estradiol (E2), such as those observed in the menstrual cycle, alter serum levels
      of soluble vascular cell adhesion molecule-1 (sVCAM-1), and whether VCAM-1
      expression is suppressed in long-term users of exogenous estrogens. The secondary
      objective was to assess the association, if any, between inflammatory cytokines
      and expression of sVCAM-1. DESIGN: Prospective collection of serum samples in
      healthy volunteers. SETTING: University hospital. PATIENTS(S): Thirty-one
      normally menstruating women and 37 oral contraceptive (OC) users. Interventions
      included serum collection in the early follicular, late follicular, and midluteal
      phases of the menstrual cycle and once in oral contraceptive users. MAIN OUTCOME
      MEASURE(S): Samples were assayed for sVCAM-1, tumor necrosis factor alpha (TNF
      alpha), and interleukin (IL)-6 by enzyme-linked immunoabsorbent assay (ELISA).
      Estradiol (E2) was measured by radioimmunoassay (RIA). RESULT(S): Oral
      contraceptive users had significantly lower serum levels of sVCAM-1 compared with
      normally menstruating women. No significant change was noted in the mean values
      of sVCAM-1 throughout the menstrual cycle, despite the significant change in
      17beta-estradiol levels. Throughout the menstrual cycle, a significant
      correlation was noted between the serum levels of TNF-alpha and sVCAM-1. The
      serum levels of IL-6 correlated with those of sVCAM-1 in the late follicular and
      midluteal phase of the cycle. Similar correlations were observed in OC users.
      CONCLUSION(S): Long-term exposure to exogenous estrogens suppresses serum levels
      of sVCAM-1. Short-term changes in endogenous estrogens, as observed during the
      menstrual cycle, may not alter VCAM-1 expression; TNF-alpha and IL-6 may play a
      role in the regulation of VCAM-1 expression in vivo.

PMID- 15866589
TI  - Granular changes in Sertoli cells in children and pubertal patients.
AB  - OBJECTIVE: To characterize lysosomes and histochemical function of granular
      Sertoli cells in developmental alterations. DESIGN: Prospective and retrospective
      study. SETTING: University hospital and research centers. PATIENT(S): Nineteen
      infantile and pubertal patients undergoing testicular biopsy; four rat testes for
      lysosomal study. INTERVENTION(S): CD-68, alpha-1-antitrypsin, vimentin, inhibin
      alpha subunit, and anti-mullerian hormone antibodies were evaluated. Morphometric
      measures in seminiferous tubules with and without granular Sertoli cells were
      obtained. Ultrastructural data of lysosomes in human and rat Sertoli cells were
      compared. MAIN OUTCOME MEASURE(S): Quantification of mean diameter of
      seminiferous tubules, tubular fertility index, and germ and Sertoli cell indexes
      were obtained in human testis. RESULT(S): Granular changes in Sertoli cells are
      due to the accumulation of large amounts of lysosomes. Vimentin immunoexpression
      in infantile and pubertal granular Sertoli cells was lower than in adjacent
      nongranular Sertoli cells. Inhibin was negative in granular cells. Anti-mullerian
      hormone-positive and -negative granular Sertoli cells were present within the
      same tubules. CONCLUSION(S): The presence of early granular changes in Sertoli
      cells in childhood and pubertal cryptorchidic patients, associated with other
      developmental alterations, suggests an intense and irreversible dysfunction of
      phagocytosis in the granular Sertoli cells. These alterations might be considered
      primary and irreversible anomalies of Sertoli cells, which might be contributing
      factors in the infertility seen in these patients.

PMID- 15866590
TI  - Effects of interstitial fallopian tube polyps on isthmic tubal diameter.
AB  - OBJECTIVE: To study the apparent association between interstitial fallopian tube
      polyps and isthmic tubal dilatation. DESIGN: Retrospective clinical study.
      SETTING: Tertiary academic medical center. PATIENT(S): Sixty-five patients with
      normal hysterosalpingograms and 40 patients with interstitial tubal polyps (25
      unilateral and 15 bilateral). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Proximal, medial, and distal isthmic diameters were measured digitally and
      normalized according to an internal standard. Polyp volumes were measured and
      divided into four groups according to increasing volume (<2 mm3, 2-5 mm3, 6-12
      mm3, >12 mm3). RESULT(S): There was a significant increase in proximal isthmic
      tubal diameter in patients with interstitial polyps. Mean diameter increased from
      0.6 mm to 0.9 mm. There was no significant change in more distal isthmic
      diameters. Larger polyps tended to be associated with larger luminal diameters.
      CONCLUSION(S): Interstitial fallopian tube polyps are associated with a
      significant increase in proximal isthmic luminal diameter as determined on
      hysterosalpingography. Although these polyps are nonobstructing and thus thought
      by most investigators not to affect fertility, their association with altered
      luminal diameter and perhaps altered function might be of clinical interest.

PMID- 15866591
TI  - Patterns of ovarian response to gonadotropin stimulation in female carriers of
      balanced translocation.
AB  - OBJECTIVE: To determine whether maternal balanced translocation is a risk factor
      for poor ovarian response to controlled ovarian hyperstimulation (COH). DESIGN: A
      retrospective analysis. SETTING: Private IVF center. PATIENT(S): All couples
      presenting to a single center for preimplantation genetic diagnosis (PGD) for
      autosomal balanced translocation in either partner from 1995 through 2001.
      INTERVENTION(S): Cycle parameters and embryology outcomes were examined and
      compared between two groups: 61 cycles in 46 women with balanced translocations
      compared with 42 cycles in 32 women whose male partner had a balanced
      translocation. MAIN OUTCOME MEASURE(S): Response to ovarian stimulation.
      RESULT(S): In couples undergoing IVF/PGD to avoid transmission of an unbalanced
      karyotype, a significantly higher proportion of women carrying balanced
      translocations (female carrier) responded very poorly (E2 on the day of hCG
      <1,000 pg/mL) to ovarian stimulation compared to women whose partner had a
      balanced translocation (male carrier) (23.0% vs. 7.1%). CONCLUSION(S): In couples
      undergoing IVF/PGD for balanced translocation, the risk for poor response to
      ovarian stimulation may be increased when the female partner carries the balanced
      translocation compared to when the male partner carries the translocation. Given
      significant embryo attrition due to chromosomal imbalance, aggressive stimulation
      should be considered if the patient does not have risk factors for ovarian
      hyperstimulation syndrome (OHSS).

PMID- 15866592
TI  - Women with ovulatory dysfunction undergoing ovarian stimulation with clomiphene
      citrate for intrauterine insemination may benefit from administration of human
      chorionic gonadotropin.
AB  - OBJECTIVE: To investigate factors that may affect pregnancy outcome following
      ovarian stimulation with clomiphene citrate (CC) combined with intrauterine
      insemination (IUI). DESIGN: Retrospective cohort study. SETTING: University
      teaching hospital. PATIENT(S): Three hundred and twenty women who underwent 691
      ovarian stimulation cycles with CC for IUI. INTERVENTION(S): Ovarian stimulation
      with CC followed by a single IUI either 24 hours after a spontaneous serum LH
      surge (>25 mIU/mL) or 36 hours after intramuscular human chorionic gonadotropin
      (hCG) administration (10,000 IU) when the largest follicle had reached a diameter
      of 17 mm. MAIN OUTCOME MEASURE(S): Clinical pregnancies. RESULT(S): Women with
      ovulatory dysfunction who received hCG had significantly higher pregnancy rates
      (24.6%) compared with women with other types of infertility. There were no
      differences in pregnancy rates between the LH surge group and the hCG group
      (14.3% vs 12.4%). A spontaneous LH surge was noted in a variety of follicular
      sizes (14 to 35 mm). There was no correlation for age, body mass index,
      follicular diameter, number of mature follicles, other sperm characteristics, and
      pregnancy outcome in either group. CONCLUSION(S): After ovarian stimulation with
      CC, IUI is equally effective 24 hours after a spontaneous LH surge or 36 hours
      after administration of hCG. Spontaneous LH surges were observed at a variety of
      follicular sizes with comparable pregnancy rates. In women with ovulatory
      dysfunction, hCG administration before insemination may be beneficial.

PMID- 15866593
TI  - Serum-free derivation of human embryonic stem cell lines on human placental
      fibroblast feeders.
AB  - OBJECTIVE: To derive new human embryonic stem cell (hESC) lines on pathogen-free
      human placental fibroblast feeders under serum-free conditions. Because the
      embryo develops in close contact with extraembryonic membranes, we hypothesized
      that placental mesenchyme might replicate the stem cell niche in situ. DESIGN: We
      isolated and characterized human placental fibroblast lines from individual
      donors and tested their ability to support growth of federally registered hESC
      lines. Moreover, we performed extensive pathogen testing to ensure their
      suitability as feeders for the derivation of therapy-grade hESCs. RESULT(S):
      Human placental fibroblasts were comparable or superior to mouse embryo
      fibroblasts as hESC feeders. We used these qualified placental fibroblasts to
      derive two new hESC lines in knockout Dulbecco's modified Eagle's medium with
      serum-free 20% knockout serum replacement. The cells, which had a normal
      karyotype, were grown for more than 25 passages, expressed markers of stemness
      including Oct-3/4, Tra 1-60, Tra 1-80, and SSEA-4, exhibited high telomerase
      activity, and differentiated in vitro and in vivo into cells derived from all
      three germ layers, confirming their pluripotency. Additionally, newly derived
      hESCs were adapted to growth on a human placental laminin substrate in a defined
      medium. CONCLUSION(S): To our knowledge, this is the first report of hESC
      derivation in the absence of serum on qualified pathogen-free human feeders.

PMID- 15866594
TI  - Progesterone and progestational compounds attenuate tumor necrosis factor alpha
      induced interleukin-8 production via nuclear factor kappa B inactivation in
      endometriotic stromal cells.
AB  - OBJECTIVE: To investigate whether and how P, dienogest (synthetic progestin), and
      danazol affected tumor necrosis factor alpha (TNFalpha)-induced interleukin-8 (IL
      8) expression in endometriotic stromal cells. DESIGN: Prospective study. SETTING:
      Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago,
      Japan. PATIENT(S): Ten patients who underwent laparoscopic surgery.
      INTERVENTION(S): Endometriotic stromal cells were obtained from chocolate cyst
      linings of the ovary. MAIN OUTCOME MEASURE(S): In the presence of TNFalpha (0.1
      ng/mL) and E2 (10(-7) mol/L), the cells were cultured in medium with P (10(-6)
      mol/L), danazol (10(-6) mol/L), or dienogest (10(-7) mol/L). The expression of
      the IL-8 gene and protein was determined by Northern blotting and ELISA,
      respectively. Activation of nuclear factor (NF)-kappaB was evaluated by
      electrophoretic mobility shift assay. RESULT(S): Adding TNFalpha (0.1 ng/mL)
      together with E2 markedly enhanced gene and protein expression of IL-8. The up
      regulation of the IL-8 gene and protein expression by TNFalpha and E2 was
      significantly reduced by the addition of P, dienogest, or danazol.
      Electrophoretic mobility shift assay revealed that incubation with TNFalpha and
      E2 induced NF-kappaB activation. Adding P, dienogest, or danazol attenuated NF
      kappaB activation. CONCLUSION(S): The present study demonstrates for the first
      time that P and progestational compounds attenuate the expression of IL-8 by
      reducing TNFalpha-induced NF-kappaB activation in endometriotic stromal cells,
      suggesting a possible molecular mechanism of hormone therapy for controlling the
      growth of endometriosis.

PMID- 15866595
TI  - Haptoglobin beta chain isoforms in the plasma and peritoneal fluid of women with
      endometriosis.
AB  - OBJECTIVE: To estimate the expression of haptoglobin (Hp) beta chain isoforms in
      the peritoneal fluid (PF) and plasma (PL) of women with and without
      endometriosis. DESIGN: Cross-sectional study. SETTING: University hospital.
      PATIENT(S): Seventy-two patients with endometriosis and 35 controls.
      INTERVENTION(S): Peritoneal fluid and PL samples were subjected to two
      dimensional gel electrophoresis, silver stained, digitally captured, and compared
      by semiquantitative computerized analysis. MAIN OUTCOME MEASURE(S): Expression of
      Hp beta chain isoforms. RESULT(S): No significant difference was observed in the
      frequency of expression of the Hp beta chain isoforms between the two groups. One
      beta chain isoform (HpbetaE; molecular weight, 38.40 +/- 0.94 kD; and isoelectric
      point, 5.63 +/- 0.17) had significantly higher expression in both the PF and PL
      of women with endometriosis than in the PF and PL of controls. No significant
      difference was observed in HpbetaE expression between women with mild (revised
      American Fertility Society [rAFS], stage I-II) and severe (rAFS, stage III-IV)
      endometriosis. In the control group, HpbetaE expression was correlated with the
      phase of the menstrual cycle. CONCLUSION(S): Women with endometriosis have higher
      PF and PL levels of HpbetaE. Further investigation should be aimed at producing
      antibodies against the HpbetaE-specific epitopes to determine whether its
      measurement may improve the clinical diagnosis of endometriosis.

PMID- 15866596
TI  - Flexible versus rigid intrauterine insemination catheters: a prospective,
      randomized, controlled study.
AB  - OBJECTIVE: To prospectively compare pregnancy rates for couples undergoing IUI by
      a single healthcare provider with random assignment to either rigid (Tomcat;
      Kendall Sovereign, Mansfield, MA) or flexible (Soft Pass; Cook, Spencer, IN)
      catheters. DESIGN: Randomized, controlled study. SETTING: Tertiary care
      infertility practice. PATIENT(S): One hundred infertile women enrolled from a
      single infertility practice who met the inclusion and exclusion criteria for IUI
      were enrolled. Of the 100 patients, 95 underwent ovarian stimulation before IUI:
      35 with clomiphene citrate alone, 60 with clomiphene citrate combined with a
      single dose of gonadotropins. INTERVENTION(S): Timed IUI was performed with
      either rigid (Tomcat) or flexible (Cook) insemination catheters. MAIN OUTCOME
      MEASURE(S): Pregnancy rate per cycle. RESULT(S): No differences were noted
      between groups for the following: age, length of infertility, day-3 FSH level,
      number of prior IUI cycles, total motile sperm count, days of abstinence,
      infertility diagnoses, insemination ratings, and stimulation protocols. No
      difference in pregnancy rates was observed between rigid and flexible catheter
      groups. CONCLUSION(S): There is no statistically significant difference between
      flexible and rigid catheters for IUI.

PMID- 15866597
TI  - Gestational carrier pregnancy with oocytes obtained during surgery for stage IIIc
      ovarian cancer after controlled ovarian stimulation.
AB  - OBJECTIVE: To report a case of gestational carrier pregnancy with oocytes from a
      stage IIIc ovarian cancer patient. DESIGN: Case report. SETTING: University
      hospital. PATIENT: A 38-year-old woman with stage IIIc ovarian cancer.
      INTERVENTION(S): Controlled ovarian stimulation, cancer surgery, and IVF-ET to a
      gestational carrier. MAIN OUTCOME MEASURE(S): Oocyte fertilization and pregnancy.
      RESULT(S): Singleton term delivery occurred after transfer of three frozen-thawed
      embryos. CONCLUSION(S): Cryopreservation of embryos derived from IVF of oocytes
      obtained from ovarian cancer patients should be an option for their future
      fertility.

PMID- 15866598
TI  - Proximal occlusion of hydrosalpinx by hysteroscopic placement of microinsert
      before in vitro fertilization-embryo transfer.
AB  - OBJECTIVE: To describe proximal occlusion of a hydrosalpinx by hysteroscopic
      placement of a microinsert before IVF-ET. DESIGN: Case report. SETTING: Health
      maintenance organization and tertiary-care assisted reproductive technology unit.
      PATIENT(S): Obese, infertile woman with pelvic adhesive disease and unilateral
      hydrosalpinx. INTERVENTION(S): Hysteroscopic placement of a microinsert into the
      proximal segment of a fallopian tube that was distally obstructed by
      hydrosalpinx. No intraoperative or postoperative complications occurred with
      hysteroscopic placement of microinsert. MAIN OUTCOME MEASURE(S): Nonincisional
      proximal tubal occlusion under local anesthesia and intravenous sedation.
      Pregnancy by IVF-ET. RESULT(S): No intraoperative or postoperative complications
      with hysteroscopic placement of microinsert were seen. After uterine transfer of
      three embryos, dichorionic-diamniotic twins were delivered by cesarean section at
      34 weeks of gestation. CONCLUSIONS(S): Hysteroscopic placement of a microinsert
      to proximally occlude a hydrosalpinx might be an alternative to laparoscopic
      proximal tubal occlusion or salpingectomy in patients with tubal disease planning
      IVF-ET.

PMID- 15866599
TI  - In vitro fertilization surrogate pregnancy in a patient who underwent radical
      hysterectomy followed by ovarian transposition, lower abdominal wall
      radiotherapy, and chemotherapy.
AB  - OBJECTIVE: To describe an IVF surrogate pregnancy from a patient who had a
      radical hysterectomy followed by excision of a laparoscopic port site
      implantation with ovarian transposition followed by abdominal wall irradiation
      and chemotherapy, which resulted in premature ovarian failure from which there
      was partial recovery. DESIGN: Case report. SETTING: Tertiary referral university
      women's hospital in Sydney, Australia and private reproductive medicine clinic in
      California. PATIENT(S): A 34-year-old woman who underwent laparoscopy for pelvic
      pain, shortly afterward followed by radical hysterectomy and pelvic lymph node
      dissection, who subsequently developed a laparoscopic port site recurrence, which
      was excised in association with ovarian transposition before abdominal wall
      irradiation and chemotherapy. INTERVENTION(S): Modified IVF treatment,
      transabdominal oocyte retrieval, embryo cryopreservation in Australia, and
      transfer to a surrogate mother in the United States. MAIN OUTCOME MEASURE(S):
      Pregnancy. RESULT(S): Miscarriage in the second cycle and a twin pregnancy in the
      fourth cycle. CONCLUSION(S): This is the first case report of ovarian stimulation
      and oocyte retrieval performed on transposed ovaries after a patient developed
      premature ovarian failure after radiotherapy and chemotherapy with subsequent
      partial ovarian recovery.

PMID- 15866600
TI  - A unique case of descending salpingitis and functioning endometrium in a
      Mullerian remnant in a woman with Mayer-Rokitansky-Kuster-Hauser syndrome.
AB  - OBJECTIVE: To describe a unique case of descending salpingitis and functioning
      endometrium in a noncavitated mullerian remnant in a patient with Mayer
      Rokitansky-Kuster-Hauser (MRKH) syndrome. DESIGN: Case report. SETTING: Second
      Department of Obstetrics and Gynecology, University of Athens, Aretaieion
      Hospital, Athens, Greece. PATIENT(S): A 25-year-old patient with MRKH syndrome
      who presented with lower abdominal pain. INTERVENTION(S): Clinical examination,
      transabdominal ultrasonography, laparoscopy, laparotomy. MAIN OUTCOME MEASURE(S):
      Clinical symptoms of salpingitis and hematometra; laparoscopic and laboratory
      confirmation. RESULT(S): Laparoscopy revealed an infection of the right salpinx,
      and surgical excision by laparotomy revealed a noncanalized mullerian remnant
      with functioning endometrium. CONCLUSION(S): Salpingitis can present in patients
      with MRKH syndrome. Probable presence of functioning endometrium must be taken
      under consideration.

PMID- 15866601
TI  - Birth of a healthy baby after transfer of blastocysts derived from cryopreserved
      human oocytes fertilized with frozen spermatozoa.
AB  - OBJECTIVE: To report the birth of a healthy baby after transfer of blastocysts
      derived from frozen eggs and frozen spermatozoa. DESIGN: Case report. SETTING:
      University-based assisted reproduction center. PATIENT(S): A 37-year-old woman
      with secondary infertility of 4 years' duration. INTERVENTION(S): Retrieved
      oocytes were cryopreserved in 1.5 M 1,2-propanediol (PROH) and 0.3 M sucrose by a
      slow freezing-rapid thawing protocol, semen cryopreservation, and insemination by
      intracytoplasmic sperm injection (ICSI) at 4 hours after thawing. MAIN OUTCOME
      MEASURE(S): Fertilization and embryo development to blastocyst stage, pregnancy,
      and outcome. RESULT(S): Ten of 14 frozen oocytes survived after thawing. Eight of
      them were fertilized by performing ICSI and three developed into 7- to 8-cell
      embryos on day 3. Two of these embryos developed into blastocysts on day 5 and
      were transferred. This resulted in a successful pregnancy and the delivery of a
      healthy baby boy. CONCLUSION(S): This case demonstrates the feasibility of
      inseminating the frozen-thawed human oocytes after 4 hours of in vitro culture
      and the zygotes derived from frozen oocytes and frozen spermatozoa can be
      cultured to blastocysts resulting in the live birth of a healthy baby boy.

PMID- 15866602
TI  - Isolated 17,20-lyase (desmolase) deficiency in a 46,XX female presenting with
      delayed puberty.
AB  - OBJECTIVE: To investigate the cause of hypergonadotropic hypogonadism. DESIGN:
      Case report and literature review. SETTING: University Departments of Pediatric
      Endocrinology and Obstetrics and Gynecology. PATIENT(S): A 13.5-year-old girl
      with absent puberty and growth retardation. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Detailed biochemical, radiological, and molecular analysis, including
      pelvic ultrasound, basal steroid hormone analysis in serum and aspirated follicle
      fluid, serum steroid measurement after ACTH (Synachten) and human chorionic
      gonadotropin (hCG) stimulation, and molecular analysis of CYP17. RESULT(S): This
      girl with hypergonadotropic hypogonadism (LH 65 U/L, FSH 50 U/L) had a 46,XX
      karyotype, small uterus and enlarged cystic ovaries, and markedly delayed bone
      age (9 years). Basal (serum, follicular) and stimulated (serum) steroid hormone
      levels were consistent with isolated 17,20-lyase deficiency whereas relatively
      normal P and 17-hydroxyprogesterone concentrations were detected together with
      very low androstenedione, T, and E(2) levels. CONCLUSION(S): Isolated 17,20-lyase
      deficiency should be considered in the differential diagnosis of
      hypergonadotropic hypogonadism in 46,XX females, and follicular fluid steroid
      analysis is a useful adjuvant test. Failure to detect mutations in CYP17 raises
      the possibility of a novel association of these phenotypes.

PMID- 15866603
TI  - Male factor infertility associated with a familial translocation
      t(1;13)(q24;q10).
AB  - We report a case of a family with one sister and one brother in which the brother
      inherited a t(1;13)(q24;q10) translocation from his mother. We describe a case
      with a clear translocation between the long arm of chromosome 1 and the long arm
      of chromosome 13. It is possible that the APOE and MTHFR genotypes and lower
      folate status may also be responsible for the above mentioned translocation.

PMID- 15866604
TI  - Interleukin-1 receptor antagonist and interleukin-1 beta polymorphisms in women
      with recurrent miscarriage.
AB  - Genotypes and allele distributions for the interleukin (IL)-1beta -511 C/T and
      the IL-1 receptor antagonist gene intron 2 tandem repeat polymorphisms were
      compared in 206 women with recurrent miscarriage and a control population. No
      significant differences were observed between the distributions of IL-1beta or IL
      1 receptor antagonist gene alleles in either the recurrent miscarriage group as a
      whole or when divided according to the cause of recurrent miscarriage compared
      with controls, which suggests that variation in the IL-1 receptor antagonist gene
      and IL-1beta genes individually does not play a role in susceptibility to
      recurrent miscarriage.

PMID- 15866605
TI  - Comparison of pituitary-ovarian function in patients who have undergone
      successful renal transplantation and healthy women.
AB  - Twenty-eight renal transplantation patients, aged 19-35 years, and 30 healthy
      women of reproductive age were enrolled into the study. Analyses revealed
      significant differences between study and control groups' midluteal serum P
      levels and between study and control groups' serum PRL levels. Although most
      renal transplantation patients have plasma estrogen and gonadotropin levels
      similar to those in healthy women, several problems, such as luteal phase defect,
      might affect transplant recipients.

PMID- 15866606
TI  - Antecubital vein venous sampling does not distort circulating levels of peptide
      and sex steroid hormones.
AB  - Simultaneous sampling from the antecubital vein (ACV) and a heated superficial
      hand vein (HSHV) at 10-minute intervals was performed in 6 women for
      determination of glucose, insulin, luteinizing hormone (LH), follicle-stimulating
      hormone (FSH), prolactin, estradiol (E2), progesterone (P4), testosterone (T),
      and dehydroepiandrosterone sulfate (DHEAS). Strong correlations were identified
      for each parameter between the two vessels, with luteinizing hormone (LH) and
      follicle-stimulating hormone (FSH) pulse patterns nearly superimposable between
      antecubital vein (ACV) and superficial hand vein (HSHV) samples.

PMID- 15866607
TI  - Association between ovarian volume and serum insulin levels in ovulatory patients
      with idiopathic hirsutism.
AB  - We assessed the influence of insulin on ovarian volume in 45 women with regular,
      ovulatory menstrual cycles, normal androgen levels, and isolated hirsutism
      (idiopathic hirsutism). Insulin levels, insulin-to-glucose ratio, and homeostasis
      model assessment (HOMA) were significantly higher in patients with ovarian volume
      >9 cm3 than in women with smaller ovaries (P<.05), and insulin levels presented a
      significant positive correlation with ovarian volume (r = 0.37, P=.02), which was
      independent of body mass index (BMI) or the luteinizing hormone/follicle
      stimulating hormone (LH/FSH) ratio.

PMID- 15866608
TI  - A polymorphism in the matrix metalloproteinase-1 gene promoter is associated with
      the presence of polycystic ovary syndrome in Caucasian women.
AB  - A common -1607 GG/G polymorphism of the matrix metalloproteinase-1 (MMP1) gene
      promoter was investigated in a series of Caucasian women with polycystic ovary
      syndrome (PCOS) and controls, by direct sequencing. In this prospective case
      control study, the odds for women with at least one mutant GG allele of the MMP1
      promoter to be diagnosed with PCOS was 2.7.

PMID- 15866609
TI  - A randomized prospective study of microdose leuprolide versus ganirelix in in
      vitro fertilization cycles for poor responders.
AB  - Forty-eight patients who met the criteria of poor response during prior
      gonadotropin stimulation were enrolled in a randomized prospective study
      comparing a gonadotropin-releasing hormone (GnRH) antagonist protocol, using
      ganirelix acetate, with a microdose GnRH agonist protocol for in vitro
      fertilization-embryo transfer (IVF-ET). This pilot study contributes to the
      literature of poor response IVF treatment protocols because the use of ganirelix
      appears to be as effective as the microdose protocol and may be a superior choice
      in terms of cost and convenience for the patient.

PMID- 15866610
TI  - New Belgian legislation regarding the limitation of transferable embryos in in
      vitro fertilization cycles does not significantly influence the pregnancy rate
      but reduces the multiple pregnancy rate in a threefold way in the Leuven
      University Fertility Center.
AB  - After the introduction of new Belgian legislation limiting the number of
      transferable embryos to prevent multiple pregnancies after assisted reproductive
      technology, the implantation rate per embryo remained stable at 26% and the
      clinical pregnancy rate per embryo transfer did not change significantly (37.5%
      before and 32.5% after legislation), whereas the multiple pregnancy rate per
      clinical pregnancy decreased threefold from 25.9% to 8.0%) in the Leuven
      University Fertility Center.

PMID- 15866611
TI  - Placental passage of metformin in women with polycystic ovary syndrome.
AB  - Metformin passes the placenta. Fetal serum levels are comparable with maternal
      values.

PMID- 15866612
TI  - GSTT1 and GSTM1 polymorphisms are associated with improvement in seminal findings
      after varicocelectomy.
AB  - To identify the best candidates for varicocelectomy, we evaluated the genetic
      polymorphism in glutathione S-transferase (GST) T1 and M1 in 38 infertile men
      with high-grade varicocele testis who underwent varicocelectomy. The response
      rate to varicocelectomy is significantly higher in patients with the GSTT1-wt
      genotype than the GSTT1-null genotype, and the response rate became higher in
      combination with the GSTM1 genotype.

PMID- 15866613
TI  - Effect of cryptorchidism and retractile testes on male factor infertility: a
      multicenter, retrospective, chart review.
AB  - This multicenter retrospective chart review study performed on 162 cryptorchid
      patients and on 34 subjects with retractile testes suggests that cryptorchidism
      and retractile testes can alter spermatogenesis, with more serious damage
      observed in bilateral cryptorchidism. This spermatogenetic impairment is probably
      related to the lack of an appropriate or timely surgical correction.

PMID- 15866615
TI  - A step backward or forward to somatic cell hybrids?

PMID- 15866616
TI  - A step backward or forward to somatic cell hybrids?

PMID- 15866617
TI  - Cryopreservation of intact ovaries--size is a variable?

PMID- 15866618
TI  - Intrasubject abstinence and quality of sperm.

PMID- 15866622
TI  - Wisconsin and Celsior solutions in renal preservation: a comparative preliminary
      study.
AB  - The aim of this study was to evaluate the efficacy of the Celsior (C) solution
      for flushing and cold storage of cadaveric renal allografts. Among 177 cadaveric
      renal allografts harvested and transplanted in our unit, 138 were preserved with
      the University of Wisconsin (W) solution and 39 with the C solution. The mean age
      of the recipients was 48.1 +/- 13.5 years, including 107 men and 70 women. The
      immunosuppressive regimens were tacrolimus-based (n = 118) or cyclosporine-based
      (n = 59). Grafts perfused with W solution were obtained from older donors than
      those perfused with C solution (42.3 +/- 16.9 vs 38.1 +/- 12.5 years; P = .017)
      and had been transplanted to older recipients (49.5 +/- 14.4 vs 43.3 +/- 13.0
      years; P = .017). The prevalence of delayed graft function (DGF) was similar in
      the 2 groups (39.1% in the W group vs 23.7% in the C group; P = .097), as well as
      the incidence of primary nonfunction grafts (5.8% vs 2.7%; P = .427). The serum
      creatinine value at 1 month was significantly higher among grafts preserved with
      W versus solution (1.9 +/- 0.9 vs 1.5 +/- 0.5 mg/dL; P = .000) as well as at 12
      months (1.63 +/- 0.5 vs 1.35 +/- 0.4 mg/dL; P = .003). There were no differences
      in graft survival at 12 months (97% C group vs 88% W group; P = .069). Our
      results showed that C solution was equivalent to W solution with respect to DGF
      and primary function of kidneys. The differences in renal function may have been
      due to differences in donor and recipient ages.

PMID- 15866623
TI  - Role of poly-(ADP-ribose) polymerase in transplant acute tubular necrosis and its
      relationship with delayed renal function.
AB  - The enzyme poly(ADP-ribose) polymerase (PARP-1) participates in the repair of DNA
      damaged by genotoxic agents such as oxygen-derived free radicals. If the
      allograft suffers pretransplant cold ischemia and subsequent ischemia-reperfusion
      injury (IR), overactivation of PARP-1 can be induced, which may lead to an
      increase in acute tubular necrosis (ATN) and a delay in total recovery of renal
      function (RRF) of the transplanted organ. We studied the nuclear expression of
      PARP-1 in tubular cells by immunohistochemistry with the monoclonal antibody
      PAR01 in 104 kidney transplant biopsies from allografts with ATN. In 50% of
      biopsies with ATN, >50% of tubular nuclei were PARP-1+; only 9.6% of biopsies
      were negative. The increase in the immunohistochemical expression of PARP-1
      showed a statistically significant relationship with the duration of cold
      ischemia, with serum creatinine levels, and with the time required to achieve
      effective diuresis (P < .0001, Spearman test). Cold ischemia of >24 hours and
      serum creatinine levels >1.7 mg/dL showed a statistically significant
      relationship with the highest PARP-1 expression levels (2.83 +/- 0.4 vs 1.36 +/-
      0.8, P < .0001, Mann-Whitney U test). We conclude that PARP-1 plays an important
      role in ATN and RRF and is related to the extent and severity of ATN and to the
      renal allograft function.

PMID- 15866624
TI  - Treatment of hepatitis C virus with interferon in hemodialysis patients awaiting
      kidney transplant.
AB  - INTRODUCTION: Hepatitis C virus (HCV) infection is associated with worsening
      disease progression after renal transplant, and to date there is no available
      treatment for use at this stage. It has therefore been recommended to treat HCV
      infection with interferon (IFN) during the dialysis period while the patient is
      on the waiting list for transplantation. METHODS: We analyzed data from 27
      patients on hemodialysis awaiting transplant, who were under IFN treatment for
      chronic HCV infection (dominant genotype, 1b). The starting regime was IFN alpha
      2b, 3 MU x 3/week (n = 20) or pegylated IFN alpha-2a, 135 mg/week (n = 7). If
      there was clearance of HCV RNA in the first 3 to 6 months, we attempted to
      prolong IFN treatment for 1 year, although in many patients the dose had to be
      reduced. A sustained response was defined as viral clearance for at least 12
      months after the end of treatment. RESULTS: Viremia was negative in 13 patients
      (48.1%) at the end of treatment, but two of these patients relapsed, to give an
      overall long-term response rate of 11 patients (40.7%) and incomplete follow-up
      in three patients. Viral clearance was not achieved in 11 patients. In three
      patients (12%), IFN had to be suspended before finishing the third month of
      therapy due to side effects (mainly pancytopenia and intolerance of a previous
      kidney graft). Seven patients showing a sustained response underwent transplant,
      maintaining a negative viremia result. CONCLUSIONS: IFN treatment was effective
      in a high proportion of dialysis patients with HCV infection, with response rates
      possibly even higher than for the general population. However, its use is
      restricted by a high incidence of side effects.

PMID- 15866625
TI  - Evaluation of renal grafts in patients with lupus nephritis as cause of end-stage
      renal disease.
AB  - INTRODUCTION: Kidney transplantation is the best option in end-stage renal
      disease (ESRD). For many years patients affected with lupus nephritis have had
      poor graft results. However, this has been changing over recent years with the
      development of new immunosuppressive drugs and a better comprehension of the
      natural evolution of the entity. METHODS: We studied 20 patients with lupus
      nephritis who received 22 kidney grafts: 15 women and five men (n = 11) who were
      treated with cyclosporine or with tacrolimus (n = 11). Secondary
      immunosuppression included mycophenolate match (MMF) (n = 13) or azathioprine (n
      = 9). We analyzed human leukocyte antigen, cold ischemia time, acute tubular
      necrosis, creatinine, cholesterol, triglycerides, glucose, blood pressure, acute
      rejection episodes, immunosuppression, infections, disease recurrences, as well
      as graft and patient survival. RESULTS: After a mean cold ischemia time of 22 +/-
      4 hours, nine patients displayed delayed graft function of an average duration 9
      +/- 4 days. At 36 +/- 35 months nine grafts were lost: two due to acute
      rejection; five to chronic allograft nephropathy; and two to venous thrombosis.
      One patient died of hemorrhagic shock. There were five cytomegalovirus
      infections. Graft survival was dependent on the type of secondary
      immunosuppression, incidence of acute rejection episodes and occurrence of
      delayed graft function. CONCLUSIONS: We found no clinical recurrence of lupus
      nephritis after transplantation and a low incidence of complications, although
      there was a trend toward thrombosis. The presence of delayed graft function,
      episodes of acute rejection, and receiving azathioprine instead of MMF as
      secondary immunosuppression were associated with poorer graft survival.

PMID- 15866626
TI  - Modulation factors of oxidative status in stable renal transplantation.
AB  - Reactive oxygen species (ROS) trigger a biomolecular alteration that causes
      functional and structural changes. In renal transplantation, there is an increase
      in oxidative phenomena related to endothelial dysfunction, inflammation, and
      atherosclerosis, the main cause of cardiovascular complications and chronic
      allograft failure. The present study was designed to assess the oxidative state
      of transplant patients with stable renal function, in order to establish
      differences in oxidative, biochemical, and clinical parameters between patients
      treated with tacrolimus versus cyclosporine. We studied 67 stable kidney
      transplant patients treated with calcineurin inhibitors who were not receiving
      cholesterol-lowering therapy, and 14 healthy subjects. Data were collected on
      biochemical parameters: lipid profile (apoA, apoB, total cholesterol and
      fractions, and triglycerides); urea; and creatinine; oxidative parameters:
      malondialdehyde (MDA) as a lipid peroxidation marker, glutathione peroxidase
      (GPx), catalase, superoxide dismutase (SOD), glutathione reductase (GR), and
      antibodies against oxidized LDL; and clinical variables. Transplanted patients
      showed a higher oxidative status (MDA increase and GPx decrease) than healthy
      subjects. The oxidative status did not differ between the cyclosporine and
      tacrolimus cohorts. Some factors during the posttransplant period, such as
      delayed graft function, cytomegalovirus infection, and microalbuminuria, which
      may damage renal function, produce a decreased antioxidant capacity (lower GPx).

PMID- 15866627
TI  - Similar impact of slow and delayed graft function on renal allograft outcome and
      function.
AB  - Kidney transplant patients can be divided into three groups, according to the
      initial graft function. First-week dialyzed patients form the delayed graft
      function (DGF) group. Nondialyzed patients are divided into slow graft function
      (SGF) or immediate graft function (IGF) according to whether the day 5 serum
      creatinine was higher versus lower than 3 mg/dL, respectively. SGF patients
      showed worse graft survival, above higher incidence of acute rejection and lower
      renal function than IGF patients, although few reports have analyzed outcomes in
      these groups. We analyzed the impact of SGF on graft survival, first-year renal
      function, and incidence of acute rejection in 291 renal transplant patients.
      Creatinine was significantly worse at 12 months for SGF and DGF than for IGF
      patients (1.9 +/- 0.8 mg/dL, 1.8 +/- 0.7 mg/dL, 1.5 +/- 0.5 mg/dL, respectively;
      P < .05). There was no difference in first-year renal function between SGF and
      DGF. The acute rejection rate was higher among the SGF than the IGF group (45% vs
      21%, P < .05), but not different from DGF patients (42%, P < .05). Graft survival
      was better among IGF than SGF or DGF patients, with no significant difference
      between the last two groups (3-year graft survival, 82%, 71%, 70%, respectively;
      log-rank test, P < .05). Kidney transplant recipients who develop SGF have a
      worse outcome than patients with IGF, similar to DGF patients. SGF patients show
      worse graft survival, worse renal function, and higher acute rejection rates than
      IGF patients, despite not needing dialysis.

PMID- 15866628
TI  - Change in serum creatinine levels between 6 and 12 months and kidney graft
      survival: influence of proteinuria.
AB  - Renal function within the first year after transplantation has been shown to be
      an important parameter influencing long-term survival. In this study, we examined
      the relationship between long-term outcome in 365 renal transplants and renal
      function in the first year, expressed as serum creatinine (SCr) level at 6 months
      and at 1 year as well as namely deltaCr, the change in SCr between 6 months and 1
      year. In addition, we examined the influence of the presence of proteinuria as a
      predictive factor for a worse evolution. Graft survival was worse among patients
      with higher deltaCr, especially among those who developed proteinuria. In a Cox
      regression analysis of long-term graft survival, both deltaCr and proteinuria
      were important predictors of half-life. The risk of graft loss when deltaCr >0.3
      was 2.65 (1.8-3.8; P < .000), whereas the risk increased to 5.67 (3.3-9.4; P <
      .00) when proteinuria was present. In conclusion, deltaCr values predict long
      term graft survival. Patients who developed proteinuria were at higher risk for
      graft loss compared with those without proteinuria. By using a combination of SCr
      and deltaCr with proteinuria, it is possible to identify a subset of transplant
      recipients with a predictably shortened half-life.

PMID- 15866629
TI  - Basiliximab (Simulect) in renal transplantation with high risk for delayed graft
      function.
AB  - BACKGROUND: Basiliximab (Simulect) is effective in reducing episodes of acute
      rejection in renal transplantation. Delayed graft function (DGF) predisposes to
      acute rejection and shortens graft survival. The aim of this study was to
      determine the effects of basiliximab in renal transplantation recipients at high
      risk for DGF. METHODS: We studied 87 patients (mean age, 59 years), 42 of whom
      received basiliximab, 20 mg before transplantation and 20 mg on day 4. This
      cohort was compared with 45 patients without basiliximab. All received
      cyclosporine (51%) or tacrolimus (49%), mycophenolate mofetil, and steroids. DGF
      was defined as the requirement for dialysis within the first week after
      transplantation or failure to improve preexisting renal function. High-risk
      factors for DGF were cold ischemia time, recipient and donor age, non-heart
      beating donor, HLA matching, and panel reactive antibody (PRA). RESULTS: The
      incidence of DGF was 18 (43%) in the basiliximab group versus 28 (62%) in the
      other patients (P = .07). When allografts from non-heart-beating donors were
      excluded, this incidence was 14 (38%) in the basiliximab group versus 28 (62%) in
      the other patients (P = .04). Regression analysis showed basiliximab to be a
      protective factor: 0.26 (range, 0.09-0.76). Basiliximab was well tolerated, and
      complications were similar in both groups. CONCLUSIONS: Basiliximab reduced the
      incidence of DGF in patients who received a high-risk allograft. It was well
      tolerated, and no adverse events were reported. The use of basiliximab may be
      considered in patients receiving an allograft who are at high risk for DGF.

PMID- 15866630
TI  - Two doses of daclizumab with delayed introduction of low-dose tacrolimus in
      elderly recipients of cadaveric renal transplants from donors >55 years of age.
AB  - BACKGROUND: Renal transplants from elderly donors have a high incidence of
      delayed graft function, which can be increased by the initial use of calcineurin
      inhibitors. Our purpose was to assess the safety and efficacy of an
      immunosuppressive regimen using anti-IL-2R antibodies and MMF that allows delayed
      introduction of low-dose tacrolimus using elderly donors to elderly recipients.
      METHODS: This observational study involved 13 transplant centers. In total there
      were 119 patients (age 60.5 +/- 6.6 years, range 50 to 77) who received a kidney
      from a donor of mean age 64 +/- 5 years (range 55 to 76), 94% of whom died from a
      CVA. Immunosuppression consisted of daclizumab (1 mg/kg in two doses;
      preoperatively and on day 14) combined with steroids, mycophenolate mofetil
      (initial dose of 2 g/d), and tacrolimus (0.1 mg/kg per day). Tacrolimus was
      introduced before day 7 (mean 5.5 days) and adjusted to a target level of 5 to 8
      ng/mL. The mean follow-up was 8 months. RESULTS: Two grafts were lost due to
      primary nonfunction and acute rejection and 48 patients (40%) required dialysis
      due to delayed graft function, although it was generally of short duration
      (median 4 days; only 2 cases >2 weeks). Acute rejection occurred in 16 patients
      (13.4%), of whom 13 were biopsy-confirmed (10.9%; Banff 1997 grades I and II).
      Three patients withdrew from the study, and three died (sepsis, accident, and
      cardiovascular event). The remaining 111 patients continued follow-up, with a
      median creatinine value of 1.5 mg/dL at 12-months. Eighty-six percent of patients
      had at least one episode of infection, half of which were urinary tract
      infections. There were 16 cases of CMV infection. CONCLUSIONS: Based on the
      initial results, our immunosuppressive regimen seems to offer good short-term
      renal function while maintaining an acceptable rejection rate and a low incidence
      of serious infections.

PMID- 15866631
TI  - Effect of new immunosuppressive regimens on cost of renal transplant maintenance
      immunosuppression.
AB  - Although newer immunosuppressive drugs control acute rejection better and have
      short-term economic advantages, their long-term cost-effectiveness is unknown. We
      studied the frequency with which different maintenance immunosuppression regimens
      were used in 3 renal transplantation cohorts treated in 1990, 1994, and 1998
      (total number, 3279). We calculated the mean annual immunosuppressive costs based
      on the true costs in a medium-sized hospital. Cyclosporine, with or without
      azathioprine, was used almost exclusively as the initial maintenance
      immunosuppressive therapy in 1990-1994. In 1998, 65% of patients received
      mycophenolate mofetil (MMF), and 20% received tacrolimus (Tac). A growing number
      of patients from 1990-1994 were converted to MMF (12%-17%) and Tac (4%-8%), while
      treatment of those from the 1998 cohort remained stable. According to year 2000
      costs, the mean immunosuppressive cost at 1 year in 1998 (5380 euros) was almost
      twice that of 1994 (2902 euros) or 1990 (2855 euros). In these 2 groups the mean
      cost was stable until 1996, then increased faster in the 1994 cohort (24.8%) than
      in the 1990 cohort (17.3%), although it remained significantly lower than that in
      1998. Correction of the evolution of drug prices and the purchasing value of the
      peseta greatly absorbed these changes. The MMF and Tac regimens showed greater
      mean graft life, but without reaching statistical significance in a multivariate
      study. The introduction of new immunosuppressive drugs has had an important
      economic effect since 1996; its cost-effectiveness is still pending confirmation
      in Spain.

PMID- 15866632
TI  - Pancreas islet transplantation in patients with type 1 diabetes mellitus after
      kidney transplantation.
AB  - Diabetic patients with end-stage renal disease have a high mortality rate. A
      combined kidney-pancreas transplant is associated with greater life expectancy.
      Pancreas islet transplantation is an alternative involving a lower degree of
      morbidity. We present two patients, of 41 and 37 years of age, with a long
      history of diabetes mellitus (C-peptide negative), both with a previous kidney
      transplant, who had been treated with 22 and 28 U of insulin/d, respectively.
      Both patients had frequent episodes of unawareness hypoglycemia. Pancreatic
      islets were infused to a total of 7809 and 19,180 IE/kg, respectively. Basal
      posttransplant C peptide levels were 2.9 and 1.3 ng/mL. After the implant, one
      patient required occasional doses of insulin, and the other patient more than 50%
      reduced dose. After the first implant neither patient had any episodes of
      unawareness hypoglycemia. HbA1c at 4 months were 6.2% and 6.9%. There were no
      transplant-related complications.

PMID- 15866633
TI  - Minimal model analysis in nondiabetic renal transplant recipients with hepatitis
      C.
AB  - INTRODUCTION: Epidemiological data suggest that hepatitis C virus (HCV) infection
      may contribute to the development of posttransplantation diabetes mellitus
      (PTDM). METHODS: We investigated the glucose metabolism in 19 renal transplant
      recipients with antiHCV antibodies and without DM according to World Health
      Organization criteria before or after transplantation. We measured insulin
      sensitivity (SI), glucose effectiveness (SG), and pancreatic insulin response
      using the frequently sampled intravenous glucose tolerance test (FSIGTT). SI and
      SG were estimated using the Bergman minimal model method and pancreatic insulin
      response was expressed as the area under insulin curve (AUIC) between 0 and 19
      minutes. RESULTS: Impaired glucose tolerance was shown in 42% of patients, some
      (31.5%) in the range of glucose intolerance (KG: 1-1.5) and others (10.5%) in the
      diabetes range (KG < 1). SI and SG were decreased in 39% and 63% of patients,
      respectively. Pancreatic insulin response revealed high variation among patients
      although showing a tendency to be enhanced. CONCLUSIONS: A high number of HCV
      positive renal transplant recipients without clinically manifest PTDM have
      impaired glucose tolerance, which suggests the future development of diabetes in
      these patients.

PMID- 15866634
TI  - Psychologic stages in renal transplant.
AB  - Health workers must be aware of the psychologic stages experienced by their
      patients. We analyzed the influence of the posttransplant time on thoughts
      (depressive and anxious) and body image perception in renal transplant
      recipients. The sample consisted of 59 adult patients (mean age +/- SD: 45.76 +/-
      11.44), divided into three groups according to the posttransplant time (1 year, 1
      to 2 years, >2 years). Subjects completed a psychosocial interview
      (sociodemographic and clinical data), the Beck's Cognitions Checklist, and the
      Garanto Self-concept Scale. Negative thoughts and body image alterations were
      increased during the first year and from the third year on, with no statistically
      significant differences between these two periods, but they were appreciable when
      these periods were compared with the 13- to 24-month interval. Renal transplant
      recipients may go through three psychologic stages after transplant: alert;
      coping; and exhaustion.

PMID- 15866635
TI  - High initial blood levels of tacrolimus in overweight renal transplant
      recipients.
AB  - For the purpose of both efficacy and safety, exposure to tacrolimus and other
      immunosuppressive drugs must be monitored, since initial levels influence the
      development of acute rejection episodes, nephrotoxicity, and posttransplantation
      diabetes mellitus. The aim of this study was to identify risk factors for
      developing high initial tacrolimus blood levels. We analyzed clinical and
      biochemical parameters of 85 renal transplant recipients receiving tacrolimus
      based immunosuppressive therapy by stratifying into subgroups of patients who
      displayed first tacrolimus concentrations higher and lower than 15 ng/mL.
      Patients with a first level of tacrolimus higher than 15 ng/mL were older (52 +/-
      13 vs 40 +/- 12 years, P < .05) and had a larger body mass index (27 +/- 4 vs 23
      +/- 3 kg/m2, P < .05) than patients with lower levels, despite receiving a lower
      weight-adjusted cumulative steroid dose (8.2 +/- 2.2 vs 9.3 +/- 2.5 mg/kg, P <
      .05). Upon logistic regression, age (RR 1.047, 95% CI 1.007 to 1.08, P = .021)
      and body mass index (RR 1.176, 95% CI 1.009 to 1.371, P = .036) remained
      significant risk factors for high initial blood levels of tacrolimus. As these
      subgroups of patients are most prone to develop posttransplantation glycemic
      disorders, attention must be paid to avoid high tacrolimus blood levels by
      diminishing initial tacrolimus doses or estimating them from ideal body weight.

PMID- 15866636
TI  - Kidney-pancreas transplants: is it so difficult to start a program?
AB  - BACKGROUND: For selected patients with type 1 diabetes mellitus and end-stage
      renal failure, simultaneous kidney-pancreas (SKP) or pancreas after kidney (PAK)
      transplantation is the treatment of choice. However, it is frequently difficult
      to start a program for fear of serious intraabdominal complications in an
      immunosuppressed patient. We review our initial experience with these
      transplantations. METHODS: Twenty-three patients (20 SKP, 3 PAK) with type 1
      diabetes mellitus received transplants between June 2000 and October 2003. All
      received immunosuppression therapy with thymoglobulin, prednisone, tacrolimus,
      and mycophenolate mofetil. The operation included portal venous drainage and
      exocrine enteric drainage. Rejections were biopsy-proved. Cytomegalovirus
      prophylaxis with gancyclovir was administered. RESULTS: The mean follow-up is 13
      months (range, 1-30 months) for recipients of mean age 39 +/- 7 years (17 men, 6
      women). Mean cold ischemia time for kidney was 10.2 +/- 3.9 hours, and for
      pancreas was 10.5 +/- 3 hours. The rate of initial graft function was 100%. Graft
      rejection rate was 8%. The repeat laparotomy rate was 53% (12 patients), with a
      mean of 0.8 procedures per patient (range, 0 to 5). At the end of follow-up,
      patient survival was 95%, kidney survival was 85%, and pancreas survival was 83%.
      Patients with a functioning graft were insulin-free, with a mean fasting glucose
      concentration of 79 +/- 7 mg/dL, hemoglobin A1C of 4.5% (range, 4% to 4.9%) C
      peptide of 5.9 ng/mL (range, 2.1 to 12 ng/mL), and a mean serum creatinine level
      of 1.6 mg/dL (range, 0.9 to 4.6 mg/dL). There was 1 death, due to
      posttransplantation lymphoproliferative disease confined to the pancreatic graft
      and abdominal sepsis at 3 months posttransplantation. CONCLUSIONS: Our results
      are similar to those of other series of SPK or PAK transplantations: low acute
      rejection rates, frequent requirement for repeat laparotomy, and good patient and
      graft survival, permitting an excellent quality of life.

PMID- 15866637
TI  - Antibodies against the donor antigen glutathione S-transferase T1 after renal
      transplantation.
AB  - The aim of the present study was to determine whether a kidney graft expressing
      the glutathione S-transferase T1 enzyme (GSTT1) could cause an alloimmune
      response in a recipient with the null GSTT1 genotype that was similar to that
      observed in liver transplant. We have found anti-GSTT1 antibodies in the sera of
      a number of patients and confirmed that only one of the four possible genetic
      combinations--positive donor/null receptor--could lead to the production of these
      antibodies. Nevertheless, the main finding of this study is that in kidney
      transplantation, this mismatch was not sufficient to trigger an immune reaction.
      Longer follow-up of the posttransplant evolution of the patients is required in
      order to clarify the contribution of the factors involved in this process.

PMID- 15866638
TI  - Effect of parathyroidectomy on renal graft function.
AB  - Some authors have reported acute impairment of renal transplant function after
      parathyroidectomy (PTx). Since 1996 PTx has been performed in 22 renal transplant
      recipients (follow-up, 24.2 +/- 15 months; serum creatinine concentration (SCr)
      pre-PTx, 1.26 +/- 0.4 mg/dL). We analyzed the serum levels of immunoreactive
      parathyroid hormone, calcitriol, calcium, phosphate, alkaline phosphatase, SCr,
      and hemoglobin, as well as proteinuria, blood pressure, and immunosuppressive
      treatment at several times: before PTx and at 7 days, 1 month, and then every 3
      months post-PTx. After PTx we observed acute renal function deterioration until
      the third post-PTx month, when SCr levels returned to baseline values. We found
      no changes in blood pressure, although there was a trend toward a reduced dosage
      of antihypertensive drugs. We compared the patients who showed more significant
      increases (>30% from baseline) in SCr (group A, n = 7) with those who did not
      (group B, n = 15). Group A had higher SCr levels pre-PTx. We observed no other
      significant differences, either pre-PTx or post-PTx. In 2 patients in group A,
      SCr returned to baseline at the third month after PTx, but in the other 5 the
      renal function impairment persisted. Taking into account this risk and that
      severe hyperparathyroidism does not revert after transplantation, it would seem
      more appropriate in such cases to perform PTx while the patient is on the waiting
      list. The causes of this renal functional impairment are not clear, but the
      patients who showed worse deterioration also had a worse renal function pre-PTx.

PMID- 15866639
TI  - Treatment with adefovir dipivoxil in a renal transplant patient with renal
      insufficiency and lamivudine-resistant hepatitis B infection.
AB  - Lamivudine is a safe, effective treatment for hepatitis B virus (HBV)
      reactivation after renal transplantation. However, prolonged lamivudine therapy
      can produce resistance to the drug. Adefovir dipivoxil (ADV) has demonstrated
      efficacy in patients with lamivudine resistance, but there is limited clinical
      experience in patients with either renal transplants or severe renal
      insufficiency. A 47-year-old man with asymptomatic HBV infection underwent renal
      transplantation in November 1995. In September 2000 lamivudine therapy was
      initiated to treat HBV reactivation. The outcome was good, with negative HBV DNA
      levels. Two years later, significant viral replication developed again. At that
      time the patient already had advanced renal insufficiency due to chronic graft
      nephropathy. The transaminase levels were increased, and the HBV DNA reached
      greater than 200,000 copies/mL by polymerase chain reaction, with development of
      ascites and cirrhosis. The patient was started on ADV 10 mg every 72 hours (dose
      adjusted to renal function). There was rapid normalization of hepatic enzymes and
      progressive decline of the viral load. HBV DNA became negative after 6 months of
      ADV treatment. The renal function has since remained stable. This case suggests
      that ADV can be safe and effective in the treatment of renal transplant patients
      with lamivudine-resistant hepatitis B, even in the presence of advanced renal
      insufficiency.

PMID- 15866640
TI  - Cost of renal transplant maintenance immunosuppression: effect of control of
      vascular risk factors.
AB  - In 3 renal transplant cohorts treated in Spain in 1990, 1994, and 1998 (total
      number, 3279), we studied the frequency of certain cardiovascular risk factors.
      Their effect on the cost of drugs was assessed from the data from 1 center; the
      mean cost of antihypertensive agents per patient-year was 349 euros, and of lipid
      lowering drugs was 294 euros. Between 1990 and 1998 the frequency of use of
      antihypertensive agents at 2 years increased from 70% to 80%, and that of lipid
      lowering agents from 12% to 46% (P < .001). Patients received various regimens of
      immunosuppression at the second year, as follows: (1) steroid-free: cyclosporine,
      2.3%; tacrolimus, 9.9%; cyclosporine plus mycophenolate, 16.2%; and tacrolimus
      plus mycophenolate, 11.8% (P < .001); (2) antihypertensive agents: 74.9% of
      patients receiving tacrolimus, with or without mycophenolate, versus 80.7% of
      those receiving cyclosporine (P = .022); (3) lipid-lowering drugs: 28.4% of
      patients receiving tacrolimus, with or without mycophenolate, versus 51.1% of
      those receiving cyclosporine (P < .001). The increase in associated drug costs
      must be added to the recent large increase in the cost for immunosuppressive
      agents, which rose from 3854 euros per year, in 1990 to 5374 euros per year in
      1998. A lower cost of associated drugs tends to lessen the overall cost of
      therapies with tacrolimus. Because cardiovascular disease is the main cause of
      death, these findings should be taken into account in the assessment of the long
      term cost-benefit ratio.

PMID- 15866641
TI  - Lumbar bone mineral density after kidney transplantation: a three-year
      prospective study.
AB  - Osteopenia is a common complication after transplantation. However, prospective
      long-term studies are scarce and most were performed in patients on cyclosporine
      and high-dose steroids. In 65 patients with functioning grafts, 41 males and 24
      females, 50 on tacrolimus-based immunosuppression and 15 on cyclosporine-based
      immunosuppression, bone mineral density (BMD) was measured in the lumbar spine
      (L2-L4) and femoral neck (FN) using dual X-ray absorptiometry (DEXA) in the first
      month after transplantation (baseline) and at 1, 2, and 3 years. At baseline, BMD
      was similar to the control population both in L2-L4 (z score = -0.421) and in FN
      (z score = -0.518). During the follow-up, 3 types of patterns were identified:
      BMD increased in L2-L4 in 25 patients (38.5%), remained stable in 20 patients
      (30.8%), and decreased in 20 patients (30.8%). BMD losses appeared mainly during
      the first year (0.964 +/- 0.162 baseline; 0.904 +/- 0.161 at 1 year, 0.886 +/-
      0.140 at 3 years; analysis of variance [ANOVA] P < .001). However, the
      improvement was maintained throughout the follow-up (0.860 +/- 0.176 g/cm2 at
      baseline; 0.901 +/- 0.161 at 1 year; 0.954 +/- 0.178 at 3 years; ANOVA P < .001)
      and there was a parallel increase of BMD in FN (0.712 +/- 0.144 at baseline;
      0.744 +/- 0.249 at 1 year; 0.826 +/- 0.184 at 3 years; ANOVA P < .01). There were
      no differences between both groups in graft function, intact parathyroid hormone
      (iPTH) levels, number of postmenopausal women, or steroid doses. About one third
      of patients had bone loss during the first year after transplantation. We were
      unable to identify any risk factor for this complication in patients on low-dose
      steroids.

PMID- 15866642
TI  - Markers of fibrosis in early biopsies of renal transplants.
AB  - Many factors are involved in the development of chronic allograft nephropathy
      (CAN). Extracellular matrix turnover depends on the balance between fibrogenic
      and antifibrogenic cytokines. The aim of our study was to analyze the presence of
      transforming growth factor beta-1 (TGF-beta1), matrix metalloproteinase-2 (MMP
      2), and mast cells in 53 early transplant biopsies using immunochemistry with
      specific monoclonal antibodies. We divided the patients into two groups depending
      on graft evolution (lost due to CAN versus functioning), renal function, presence
      of proteinuria, and graft survival. There were no differences in the demographic
      or immunological data. Renal function was worse and proteinuria greater among the
      group with CAN. The presence of mast cells was similar in both groups, but TGF
      beta1 was expressed more and MMP-2 less in the CAN group. We observed a negative
      correlation between donor age and mast cells, and a positive correlation between
      TGF-beta1 and MMP-2. Grafts from younger donors showed better renal function,
      less proteinuria, greater graft survival, and less frequent development of CAN.
      According to our experience, cytokines involved in matrix turnover are expressed
      in early stages, correlating with donor age. The expressions of TGF-beta1 and MMP
      2 seem to be important for the development of fibrosis in CAN.

PMID- 15866643
TI  - Alendronate in kidney transplant patients: a single-center experience.
AB  - INTRODUCTION: Osteoporosis following a renal transplant is an important cause of
      morbidity. Several studies have demonstrated the efficiency of diphosphonates for
      the prevention and treatment of osteoporosis. METHODS: We evaluated the effect of
      alendronate treatment on bone mineral density (BMD) in patients with osteoporosis
      (lumbar spine and/or hip t-scores < or = -2.5). Two study groups were
      established: group A (n = 13), patients treated orally with vitamin D, calcium,
      and alendronate (70 mg/week) and group B (n = 12) patients receiving only vitamin
      D and calcium. The immunosuppression regimen mostly used was steroids and
      cyclosporine. BMD was determined at the lumbar spine and hip using a Hologic 4500
      QDR densitometer at the start of treatment and after 1 year. RESULTS: The study
      groups showed no significant differences in age, sex, menopause, or transplant
      time. Group A received a mean of 1.80 +/- 1.3 microg vitamin D/week and 1.3 +/-
      2.1 g calcium/d, compared to 1.1 +/- 1 microg and 1.25 +/- 2.3 g, respectively
      for group B (NS). After a mean of 411.15 +/- 107.75 days of treatment, a
      significant increase in BMD at the femoral neck was recorded in group A, but not
      at the level of the spine (+5.57% +/- 3.5%, P < .05 and -0.42% +/- 12%, NS,
      respectively). No significant changes were observed in group B (-1.45% +/- 8%
      femoral neck and +1.69% +/- 3.5% hip, NS). Dyspepsia was reported by 7% of
      patients. CONCLUSIONS: In this preliminary analysis, alendronate produced,
      improvements are so far limited to an increased BMD in the hip.

PMID- 15866644
TI  - Plasmapheresis for the prophylaxis and treatment of recurrent focal segmental
      glomerulosclerosis following renal transplant.
AB  - We evaluated 10 patients with primary focal segmental glomerulosclerosis (FSGS)
      treated with plasmapheresis (PS) following renal transplantation. Three patients
      lost their first graft due to FSGS recurrence. In seven patients, PS was
      indicated as treatment for probable recurrence defined as the onset of
      proteinuria above 1 g/24 hours. In the remaining three patients, treatment was
      started in the first week posttransplant as prophylaxis against recurrence. The
      PS protocol was 17 sessions with the exchange of 2.5 L of plasma for 5% albumin
      over 10 to 12 weeks. Losartan (25 to 100 mg/d) was given to most patients at the
      end of PS treatment. The mean follow-up time after PS was 10 months. All patients
      currently have a functioning graft. A full response to treatment, defined as
      persistently reduced proteinuria to less than 500 mg/24 hours or the lack of
      recurrence in prophylactic treatment, was achieved in six patients. Three
      patients showed a partial decrease in proteinuria (to less than 1 g/24 hours).
      One patient failed to respond and still has nephrotic range proteinuria. No
      adverse effects of PS were recorded. A prompt start of PS combined with the use
      of losartan yields good results in the prophylaxis and treatment of recurrent
      FSGS following renal transplant in terms of quickly reduced proteinuria. Given
      the natural course of FSGS, a longer follow-up is needed to estimate the impact
      of PS on graft survival.

PMID- 15866645
TI  - Prospective histopathological analysis of hepatocellular carcinoma treated with
      percutaneous ethanol injection in patients on the waiting list for liver
      transplantation.
AB  - INTRODUCTION: Liver transplantation (LT) improves survival in selected patients
      suffering from hepatocellular carcinoma (HCC). Unfortunately, the long time lapse
      between indication and LT may cause tumor progression. Thus, percutaneous ethanol
      injection (PEI) has been proposed as adjuvant therapy of HCC in patients awaiting
      LT. The efficacy of PEI assessed using histopathological analysis of hepatectomy
      specimens has not been adequately evaluated. PATIENTS AND METHODS: Twenty-nine
      nodules of HCC in 27 patients (21 men; mean age, 58.1 +/- 7.3 years) listed for
      LT were treated with PEI. Pretreatment mean serum alpha-fetoprotein (AFP) was 11
      +/- 13.4 ng/mL. Mean tumor diameter was 30.8 +/- 12.9 mm. Data from the explanted
      livers after transplantation included percentage tumor necrosis, presence of
      satellite and distant nodules, vascular invasion, tumor capsule, and grade of
      differentiation. RESULTS: Nineteen patients with 20 treated lesions underwent
      transplantation. The median interval PEI-LT was 3 months. Complete necrosis was
      observed in 13 nodules (65%). Satellite nodules were present in 10% of lesions.
      Previously unrecognized distant lesions were seen in 15.8% of patients. Only 1
      nodule presented microscopic vascular invasion. Most HCC were well differentiated
      (90%), and completely encapsulated (80%). No tumor-related deaths occurred.
      Seventeen patients are alive and recurrence-free after a median follow-up of 15
      months. CONCLUSIONS: PEI may achieve significant necrosis in cases of HCC
      awaiting LT. Nevertheless, previously unrecognized satellite and distant lesions
      may be observed. Further studies are needed to evaluate the influence of tumor
      necrosis on overall survival of these patients.

PMID- 15866646
TI  - Therapy of intractable pruritus with MARS.
AB  - INTRODUCTION: Pruritus is the most disabling symptom in patients with cholestatic
      liver diseases. Many drug therapies have been used for the treatment of these
      diseases, with different outcomes. The molecular adsorbent recirculating system
      (MARS) has been used in the treatment of intractable pruritus in cholestatic
      syndromes. We report our experience with MARS in 3 patients with intractable
      pruritus on the waiting list: 2 liver transplant recipients and a patient with
      primary biliary cirrhosis. PATIENTS AND RESULTS: Two middle-aged women and 1
      middle-aged man, who were recipients of an orthotopic liver transplant for
      primary biliary cirrhosis, underwent three (n = 2) and two (n = 1) 6-hour
      sessions of MARS due to medically uncontrollable pruritus. All noted marked
      improvement of pruritus, with decreased bilirubin levels, but this improvement
      lasted only a few days in all cases. We observed no changes in transaminase or
      albumin levels, or prothrombin time. Complications included an episode of angina
      due to anemia caused by jugular catheter bleeding, and thrombocytopenia in all
      patients. CONCLUSIONS: MARS is an effective treatment for intractable pruritus in
      cholestatic liver diseases, although its beneficial effect is short. This
      extracorporeal liver device is safe, because most related adverse events are
      mild.

PMID- 15866647
TI  - Effectiveness of pegylated interferon and ribavirin in patients with liver HCV
      cirrhosis.
AB  - Clearance of HCV before transplantation could avoid recurrence of hepatitis C in
      the liver allograft, thereby improving graft and patient survival. We report our
      experience with combined therapy for patients with HCV cirrhosis, including 12
      patients with biopsy-proven liver cirrhosis (n = 7) or previous cirrhotic
      complications (n = 5). The Child-Pugh score was A in eight patients and B in
      four. Two patients had hepatocellular carcinoma. Genotype distribution was 1a (n
      = 2), 1b (n = 8) or 3 (n = 1). Patients received peginterferon alpha2b (1.5
      microg/kg once weekly) and ribavirin (10.6 g/kg per day) for 48 weeks (genotype
      1) or 24 weeks (genotype 3). Twenty-one months after beginning therapy all the
      patients remained alive; three have undergone liver transplantation. In one
      patient treatment was discontinued after 2 months due to cachexia. End-of
      treatment virologic response was achieved in five patients (41.7%) and sustained
      virologic response in three patients (25%). Patients who cleared the virus had
      negative PCR 4 weeks after beginning therapy. All patients had adverse events.
      The most common clinical events were asthenia, weight loss, fever, and anorexia.
      Infectious complications resolved in three patients (25%). Hematologic events
      were common. Seven of 11 patients (63.6%) who completed therapy required dose
      reduction. We conclude that therapy with peginterferon and ribavirin in patients
      with HCV cirrhosis has a similar effectiveness to previous treatments. A
      virologic response 1 month after the beginning of therapy could be a main
      predictor of a sustained response.

PMID- 15866648
TI  - Efficacy of hepatocellular carcinoma locoregional therapies on patients waiting
      for liver transplantation.
AB  - The aim of this study was to evaluate the efficacy of different locoregional
      therapies in patients with HCC on the waiting list for liver transplantation.
      From October 2001 to July 2003, 13 patients, all men, with HCC diagnosed by
      cytology, were transplanted at our center. Locoregional therapies were
      percutaneous ethanol injection (PEI), transcatheter hepatic arterial
      chemoembolization (TACE), and radiofrequency microwave ablation (RFA). PEI was
      employed in seven patients, TACE in five (one of them associated with PEI) and
      RFA in one. Efficacy was evaluated by determining the percentage of tumoral
      necrosis in the liver explant. Five tumors were T4, four T3, three T2, and one
      T1. Ten were well differentiated, two moderately differentiated, and one
      undifferentiated. One patient died due to primary graft malfunction. After a
      median posttransplant follow-up of 15 months, 12 patients are alive with no sign
      of tumor recurrence. Most patients with solitary nodules <4 cm who received PEI
      had 90% to 100% tumor necrosis. Larger tumors had 25% to 30% necrosis. TACE was
      employed in six patients with large and/or multiple tumors, obtaining 20% to 50%
      tumor necrosis. RFA was employed in one case obtaining 85% necrosis (tumor of 4
      cm). No serious complications occurred with any technique. According to our
      experience, PEI and RFA are effective locoregional therapies to treat
      hepatocellular carcinomas of <4 cm in patients on the waiting list. For larger
      tumors, their association with other techniques, such as TACE, seems adequate.

PMID- 15866649
TI  - Prevalence of hepatitis C virus genotypes in a Spanish liver transplant unit.
AB  - INTRODUCTION: Among the at least six major identified genotypes of HCV, genotype
      1b, the one associated with a poorer prognosis, is the most prevalent in Spain.
      We aimed to compare the distribution of hepatitis C virus genotypes in our liver
      transplant unit with that of the other HCV patients at our institution (n = 413)
      in order to assess whether genotype 1b is more prevalent among patients with more
      severe liver disease. PATIENTS AND METHODS: One hundred eight patients of mean
      age 56 years included 81 (75%) OLT recipients and 27 (25%) with HCV cirrhosis.
      Determination of HCV genotypes was made with the Inno-LiPA HCV III. RESULTS: The
      overall distribution of genotypes was: 1b, 93 patients (86.1%); 1a; eight
      patients (7.4%); 3, four patients (3.7%); 4; two patients (1.9%), and 2; one
      patient (0.9%). The distribution was similar among patients with cirrhosis and
      OLT. Genotype 1b patients were older. Eleven (78.6%) of 14 patients with
      hepatocellular carcinoma had genotype 1b. In the control group the distribution
      was: 1b, 287 patients (69.5%); 1a, 54 patients (12.1%); 3, 41 patients (9.9%); 4,
      20 patients (4.8%), and genotype 2, 11 patients (2.7%). This differences in the
      distribution of genotypes between our population and the control group was
      statistically significant (P < .001). CONCLUSIONS: Genotype 1b, the most
      prevalent genotype in our liver transplant unit, included older patients in whom
      hepatocellular carcinoma was common, perhaps due to their higher prevalence of
      cirrhosis.

PMID- 15866650
TI  - Liver transplant results for hepatocellular carcinoma applying strict
      preoperative selection criteria.
AB  - INTRODUCTION: Liver transplantation is currently the best therapeutic option for
      small hepatocellular carcinoma (HC) in selected cirrhotic patients. The main aim
      of this study was to analyze the results of a recent series of liver transplant
      cirrhotic patients with small HC applying strict preoperative selection criteria.
      PATIENTS AND METHODS: During a period of 6 years we performed 53 liver
      transplants with a final diagnosis of HC on cirrhosis. The selection criteria for
      liver transplantation (LT) by modern imaging techniques were the Milan criteria
      (TNM I and II of the modified classification). RESULTS: Of the 53 patients, 44
      (83%) were transplanted with preoperatively known HC, and 9 (17%) with incidental
      HC. The mean time on the waiting list was 74 +/- 62 days. Despite using strict
      selection criteria, 23 patients (43%) exceeded the Milan criteria in the specimen
      and 17 (32%) even exceeded the extended criteria of the UCSF. With a mean follow
      up of 2 years, only two patients have developed recurrences. The overall survival
      at 1, 3, and 5 years was 80%, 70%, and 70%, respectively. The survival of
      patients that exceeded the Milan or USF criteria at 1, 3, and 5 years was 72% and
      76%; 67% and 69%; 67% and 69%, respectively. CONCLUSIONS: The results of liver
      transplantation for HC are excellent when applying strict preoperative selection
      criteria. The current imaging methods lead to a considerable infrastaging
      percentage (30% to 40%), extending the indications for liver transplant due to HC
      beyond the scope that clinical reports would justify.

PMID- 15866651
TI  - Results of liver transplantation in patients with previous portosystemic shunts.
AB  - INTRODUCTION: Although liver transplantation is performed successfully in some
      patients with previous portosystemic shunts (PSS), these surgical procedures have
      been considered a relative contraindication for orthotopic liver transplantation
      (OLT). We aimed to determine whether a previous PSS worsens the prognosis of
      patients who undergo OLT. PATIENTS AND METHODS: Between March 1986 and October
      2003, 520 liver transplants were performed in 467 patients in our center.
      Thirteen patients had undergone a PSS before OLT. The types of PSS were:
      portocaval (n = 8), splenorenal (n = 3), mesocaval (n = 1), and portoatrial (n =
      1). We compared patients with previous PSS (cases) and the three patients with an
      OLT immediately before each case (controls). We analyzed the following variables:
      age, Child-Pugh stage, pretransplant liver disease, surgical times, transfusion
      requirements, infections, intensive care unit (ICU) stay, postoperative
      evolution, and survival. RESULTS: Age, Child-Pugh stage, and pretransplant liver
      disease were similar in both groups. There were no statistical differences in
      age, surgical times, ischemia time, anhepatic phase, transfusion requirements,
      ICU stay, infections, or hospital stay. The postoperative course was similar in
      both groups. Long-term survival was 84.62% in cases versus 78.5% in controls.
      CONCLUSIONS: Previous PSS should not be considered a contraindication for liver
      transplantation, even though this group of patients involves a special surgical
      challenge.

PMID- 15866652
TI  - Doppler ultrasonography for the assessment of tumor necrosis after percutaneous
      ethanol injection prior to liver transplantation as adjuvant therapy of
      hepatocellular carcinoma.
AB  - INTRODUCTION: Percutaneous ethanol injection (PEI) is considered to be a curative
      treatment for hepatocellular carcinoma (HCC). The imaging technique of choice for
      the assessment of local response after PEI has not been well defined, but helical
      computerized tomography (hCT) has been recommended. The aim of this study was to
      assess the accuracy of Doppler ultrasonography (US) for evaluation of tumor
      necrosis after PEI. PATIENTS AND METHODS: Twenty-one patients with single HCC
      listed for liver transplantation underwent multisession US-guided PEI. Liver
      Doppler US was done at the 4th week after PEI. Complete response was defined as
      the absence of any intratumoral Doppler signal. The liver was analyzed in
      transplant recipients during the follow-up. Complete pathological response was
      defined as necrosis > or = 90% of total tumor volume. Histological and
      sonographic findings were compared. RESULTS: Twelve patients underwent
      transplantation (9 men, mean age 60 +/- 5.2 years). Nine of these (75%) showed a
      complete ultrasonographic response. In the explanted liver, complete necrosis was
      present in 6 nodules, and incomplete necrosis was seen in the remaining 6 cases.
      In comparison with histology, Doppler US showed values of sensitivity,
      specificity, positive predictive values, and negative predictive values of 50%,
      100%, 100%, and 60%, respectively. Overall accuracy was 75%. CONCLUSIONS: In our
      series, Doppler US showed low sensitivity but high specificity in the assessment
      of HCC necrosis after PEI. The ultrasonographic finding of complete response
      requires hCT for confirmation, but the presence in Doppler US of neoplastic
      viable tissue is enough to indicate a further cycle of PEI.

PMID- 15866653
TI  - Lack of association of recipient MCP-1 gene promoter polymorphism with acute
      graft rejection after orthotopic liver transplantation.
AB  - Acute graft rejection after orthotopic liver transplantation (OLT) is associated
      with leukocyte infiltration of the graft. Monocyte chemoattractant protein-1 (MCP
      1) is a beta-chemokine involved in the attraction and accumulation of mononuclear
      granulocytes toward sites of inflammation. A biallelic polymorphism (G/A) at
      position -2518 of the MCP-1 gene has been described. Cells obtained from
      individuals with the GG or AG genotypes have been found to produce more MCP-1
      than those obtained from individuals with the AA genotype. The goal of this study
      was to assess the possible association between this polymorphism and
      susceptibility to acute graft rejection after OLT. One hundred fifty Caucasian
      liver transplant recipients from the South of Spain underwent genotyping using a
      polymerase chain reaction (PCR) amplification followed by restriction fragment
      length polymorphism (RFLP). No significant differences were observed when
      patients with versus without acute rejection episodes were compared for the
      distribution of -2518 MCP-1 genotypes. The present study supports the lack of
      involvement of polymorphism at position -2518 (A/G) of the MCP-1 gene on the
      susceptibility to acute allograft rejection among OLT recipients.

PMID- 15866655
TI  - Psychological adaptation of liver transplant recipients.
AB  - We analyzed the influence of two variables (place of hospitalization of the
      patients and the mental health of relatives) on symptoms of anxiety and
      depression in liver transplant patients. The subject groups were made up of 48
      liver transplant recipients (mean age 51.15; SD = 8.57) and their close
      relatives. The tests applied were a psychosocial questionnaire, and the two
      tests: "The Hospital Anxiety and Depression Scale" and "The Leeds Scales for the
      Self-Assessment of Anxiety and Depression." The liver transplant recipients
      showed more symptoms of depression when they were in the intensive care unit
      (ICU) and more symptoms of anxiety in the post-ICU phase when their close
      relatives were more depressed in that phase. The place of hospitalization of the
      patients and the mental health of relatives influenced the symptoms of anxiety
      and depression in liver transplant recipients.

PMID- 15866654
TI  - Preoperative factors and models predicting mortality in liver transplantation.
AB  - We analyzed preoperative factors related to postoperative mortality after liver
      transplantation among a cohort of 268 consecutive liver transplant patients over
      6 years. We studied the impact of 10 recipient variables, 14 donor features, and
      three operative aspects. We also studied the correlation with death and survival
      using various predictive scores (Child, Cordoba Score, MELD, and UCLA).
      Univariate analysis showed that the factors with a significant association with
      postoperative mortality were the use of noradrenaline in the donor, total
      ischemia time (>12 hours), and transplant indication (hepatitis C virus versus
      the rest). Multivariate analysis of mortality showed the impact of female donor
      sex, recipients over >60 years, recipient albumin less than 2.8, and total graft
      ischemia time more than 12 hours. Univariate analysis of 1-year survival showed a
      statistically significant relation with D/R gender similarity, as well as donor
      GOT (>170) and GPT (>140) values. Multivariate analysis of 1-year survival showed
      donor GOT (>170) and donor/recipient gender similarity to be significant.
      Concerning the prediction models, Child-Pugh (AB versus C) best determined
      postoperative mortality (P < .006), MELD was predictive of 1-year survival (P <
      .03). The most important variables related to postoperative mortality were total
      ischemia time over 12 hours, recipient albumin less than 2.8, and age above 60
      years. The variable with most impact on 1-year survival was the degree of graft
      hepatocyte lesion as determined by GOT. The Child-Pugh system is still the best
      indicator of postoperative mortality, although MELD may also be a good predictor
      of survival.

PMID- 15866656
TI  - Liver transplantation at the Cuban Center for Medical and Surgical Research.
AB  - From July 4, 1999, when a liver transplantation program was started in Cuba, to
      October 2003, 66 procedures had been performed in 60 patients. The most frequent
      reason was cirrhosis caused by hepatitis C virus (29%), and alcoholic cirrhosis
      (22%). Two patients received simultaneous liver-kidney transplants. Half of the
      patients were men. Patient ages ranged from 12 to 62 years; the average surgical
      time was 6 hours; and cold ischemia time was 4 to 14 hours. The average blood
      consumption was 2033 mL; 2900 mL of plasma and 8 units of platelets were used in
      7 cases. Immunosuppression was mainly cyclosporine (Neoral), mycophenolate
      mofetil or azathioprine, and prednisone. Acute cellular rejections were treated
      in almost all cases with 3 doses of methylprednisolone. The most frequent
      complications were biliary (24%), hepatic arterial thrombosis (12%), post
      surgical bleeding (10%), acute cellular rejection (24%), and ductopenic rejection
      (2%). The overall 1-year survival rate was 73.7%.

PMID- 15866657
TI  - Adefovir dipivoxil therapy in liver transplant recipients with lamivudine
      resistant hepatitis B virus.
AB  - Hepatitis B virus (HBV) infection is the leading cause of cirrhosis worldwide.
      One effective strategy to prevent recurrence or transmission of HBV infection
      after liver transplantation exists is prescription of Lamivudine, although it is
      associated with high resistance rates. Adefovir dipivoxil (AD) is a nucleotide
      analogue of adenosine that has achieved significant results in virologic,
      biochemical, and clinical parameters in lamivudine-resistant HBV-infected
      patients. Between 1990 and 2003 7 adult recipients of orthotopic liver
      transplants who experienced lamivudine-resistant HBV infection
      (pretransplantation or posttransplantation) were enrolled in a prospective study
      to administer AD for 48 weeks. At baseline they showed serum HBV DNA between 2.2
      x 10(6) and 1.1 x 10(8) copies/mL. After 48 weeks of AD treatment, the median
      time-weighted average change in serum HBV DNA (log 10 copies/mL) was -3.19 (SD,
      1.65). In 3 patients with HBV, DNA was undetectable (<400 copies/mL) at the end
      of the follow-up. HBe antigen seroconversion was observed in 1 patient. No
      significant adverse effects were recorded, except for renal functional impairment
      in 1 patient who had previous renal insufficiency. In our study, adefovir was an
      effective drug to suppression HBV replication in liver transplant recipients with
      lamivudine-resistant HBV. Excluding renal function abnormalities, tolerance of
      the drug was excellent. None of the patients developed resistance to adefovir.
      Therapy with AD in liver transplant recipients is effective and safe, although
      renal function should be monitored closely.

PMID- 15866658
TI  - Mycophenolate mofetil-induced neutropenia in liver transplantation.
AB  - BACKGROUND: Mycophenolate mofetil (MMF) is a potent, safe immunosuppressive agent
      for rescue therapy of acute and chronic rejection in orthotopic liver transplant
      recipients. It helps to reduce the serious toxic side effects of calcineurin
      inhibitors (CNIs). The side effects of MMF, such as bone marrow toxicity, have
      been reported. Herein we report four patients who underwent liver transplantation
      and developed neutropenia while receiving MMF. METHODS: Between April 2002 and
      October 2003, we performed 24 liver transplants in 25 patients. Eighteen patients
      were given MMF for the following reasons: renal failure in nine (50%); treatment
      of acute rejection in three (16.6%); primary prophylaxis of rejection in five
      (27.7%); and CNI withdrawal in one (5.5%). RESULTS: Of the 18 patients treated
      with MMF, there were 11 men (61.1%) and seven women (38.8%), with an overall mean
      age of 55.5 years. This therapy was ceased in four patients due to neutropenia
      (22%). Discontinuation of MMF was followed by a rapid and spontaneous rise in
      neutrophils in two patients. Granulocyte colony stimulating factor (GCSF) was
      administered to one patient and in another a bone marrow biopsy was performed due
      to persistent anemia, leukopenia, and thrombocytopenia. The mean time from
      starting MMF to the development of neutropenia was 4 months. Only the third
      patient showed elevated levels of MMF. CONCLUSIONS: MMF is a potent
      immunosuppressive agent in liver transplantation. However, because serious
      hematologic toxicity has been reported, we recommend caution in administration
      and careful monitoring of blood levels.

PMID- 15866659
TI  - Mycotic pseudoaneurysms after liver transplantation.
AB  - The most frequent etiology of visceral artery aneurysms is arteriosclerosis, but
      vascular manipulation during hepatic transplantation may also cause a mycotic
      pseudoaneurysm. Treatment with embolization, stents or percutaneous thrombin
      injection have been recommended but surgical revascularization is indicated when
      interventional techniques fail. A 43-year-old man with hepatitis C virus
      cirrhosis who underwent orthotopic liver transplantation from a cadaveric donor
      was treated with cyclosporine, mycophenolate, and steroids and was discharged
      from hospital at 35 days. Two months later he was readmitted with a febrile
      syndrome. Abdominal computed tomography showed necrosis of hepatic segments IV,
      V, and VI. Magnetic resonance imaging and angiography revealed partial thrombosis
      of the hepatic artery and stenosis of the portal anastomosis secondary to an
      aneurysm of the hepatic artery. A few hours after the radiological diagnosis, the
      patient suffered a bout of upper gastrointestinal bleeding and shock. Emergency
      surgery revealed a mycotic pseudoaneurysm of the common hepatic artery, which had
      ruptured into the bile tract with hemobilia. The liver graft was removed because
      of severe necrosis of the right liver. The patient died awaiting a new liver
      transplantation.

PMID- 15866660
TI  - Circadian variability of blood pressure in liver transplant recipients without
      antihypertensive therapy.
AB  - Hypertension is a frequent cardiovascular risk factor in liver transplant
      recipients. The usefulness of ambulatory blood pressure monitoring (ABPM) in
      these patients is unknown. This study was aimed at evaluating the circadian
      rhythms of blood pressure in liver allograft recipients. In 53 liver transplant
      patients blood pressure was measured with the Spacelabs device program. No
      patient received antihypertensive therapy for at least 15 days beforehand.
      Clinical blood pressure measurement showed 26 patients to be hypertensive. Of
      these, ABPM verified the diagnosis in 23. Overall, 72% of the patients were
      hypertensive, and 39.5% showed a nondipper pattern. Diastolic hypertension was
      more frequent than systolic hypertension. No differences were found in renal
      function, immunosuppressive therapy, or corticosteroids.

PMID- 15866661
TI  - Pediatric lung transplantation.
AB  - INTRODUCTION: Pediatric lung transplantation (LT) was started in Spain in 1996 at
      our institution. We compare the results of pediatric LT with those in adult
      patients. METHODS: A retrospective review of LT patients from 1993 to 2003
      included demographic donor and recipient data, pulmonary function, gas exchange
      parameters, complications, episodes of rejection and pneumonia, as well as
      survival. Patients were divided into 2 groups: pediatric (<16 years) and adult
      (>16 years) LT patients. RESULTS: Of 165 LTs performed, 23 recipients were
      pediatric patients (10 boys, 13 girls; mean age, 11.9 +/- 2.9 years [range, 5-16
      years]). The indications were cystic fibrosis (n = 21), pulmonary fibrosis (n =
      1), and Kartagener syndrome (n = 1). The actuarial survival rate was 73%, 67%,
      and 62% at 1, 3, and 8 years post-LT in children, versus 67%, 56%, and 41% at 1,
      3, and 8 years post-LT in adult patients (P = NS). Of the pediatric patients, 35%
      required mechanical ventilation preoperatively (P < .001). Pediatric patients
      showed a higher incidence of pneumonia (P < .01) and acute rejection episodes (P
      = .02) during the first month post-LT, and longer stays in the intensive care
      unit (P = .02). Pediatric patients displayed more immunosuppression-related
      adverse effects: diabetes (P = .04), neuropathy (P < .01), and hirsutism (P <
      .001). In children, arterial oxygen tension improved, from 51 mm Hg pre-LT to 93
      mm Hg at 5 years post-LT. Forced expiratory volume in 1 second improved from 28%
      pre-LT to 84% at 5 years post-LT. CONCLUSION: In children, LT is a high-risk
      procedure because of the critical status of these patients. However, the results
      of pediatric LT are similar to those in adults, but with better long-term
      survival.

PMID- 15866662
TI  - Analysis of lung transplant recipients surviving beyond 5 years.
AB  - INTRODUCTION: We started lung transplantation (LT) in October 1993 and review the
      status of recipients who have survived beyond 5 years. METHODS: A retrospective
      review of patients undergoing LT from October 1993 to October 1998 included
      pulmonary function data, incidence of bronchiolitis obliterans syndrome (BOS),
      functional status, and survival. RESULTS: Of 73 transplantations 41 (56%)
      patients have survived beyond 5 years (study group), including 23 men and 18
      women of age 33.2 +/- 15.6 years. Indications for LT were as follows: cystic
      fibrosis (n = 16), emphysema (n = 13), pulmonary fibrosis (n = 8), and other (n =
      4). Actuarial survival at 5, 7, and 9 years was 56%, 53%, and 43%, respectively.
      Freedom from BOS was 63%, 56%, and 50% at 5, 7, and 9 years, respectively. The
      median percent predicted FEV1 was 67%, 56%, and 56%, respectively. Also, 79% of
      recipients had no limitations in their daily activities; 65% were active and
      working. Only 5% of patients showed some degree of limitation at 5 years
      posttransplantation. When survivors beyond 5 years were compared with
      nonsurvivors beyond 5 years, differences were observed: nonsurvivors more
      frequently required bypass (P = .01), experienced longer postoperative intubation
      times (P = .01), and exhibited lower PaO2 at 12 months posttransplantation (P <
      .01). CONCLUSION: Our data show good survival rates among patients surviving
      beyond 5 years after LT, with a moderate incidence of BOS at 9 years
      posttransplantation. Despite the incidence of BOS, these patients have good
      pulmonary function and activity status.

PMID- 15866663
TI  - Pulmonary tailoring and lobar transplantation to overcome size disparities in
      lung transplantation.
AB  - Size matching between donors and recipients represents one of the organ
      distribution criteria widely accepted by lung transplant teams. However, in some
      cases it is not possible to allocate a donor to the corresponding size-compatible
      recipient. To avoid possible complications derived from the implantation of
      oversized lungs into smaller recipients, surgical procedures such as pulmonary
      tailoring and lobar transplantation have been advocated. We review our experience
      in 13 patients undergoing volume reduction of the lung graft at the time of
      transplantation, either by nonanatomical lung volume reduction or by lobar
      transplantation. There were no significant differences between lung-downsized
      patients and standard lung transplantation patients in terms of donor
      characteristics, surgical and postoperative complications, functional outcome,
      and survival. We conclude that downsizing the lung graft either by nonanatomical
      resection or lobar transplantation is safe and reliable to overcome size
      disparities between donor and recipients, with no additional morbidity and with
      similar early and midterm outcomes to those in standard lung transplants.

PMID- 15866664
TI  - Long-term results of lung transplantation for emphysema.
AB  - INTRODUCTION: We sought to assess the differences between lung transplantation
      (LT) to treat emphysema, versus other pulmonary diseases. METHODS: This
      retrospective review of lung transplantations (LTs) performed from October 1993
      to September 2003, included donor and recipient demographic data, pulmonary
      function, oxygenation, postoperative complications, incidence of rejection and
      pneumonia, and survival. RESULTS: Of 159 LTs performed the 39 transplanted to
      treat emphysema (24.4%), were in 33 men and 6 women of age 50.9 +/- 8.7 years
      (men, 25 to 65 years). There were differences between the emphysema vs other
      groups in terms of age (P < .001), gender (P = .001), need for bypass (P = .004),
      and immediate posttransplantation oxygenation index (P = .001). Perioperative
      mortality tended to be lower among patients with emphysema (2.7% vs 10.8%; P =
      .131). The incidences of complications and acute rejections was similar. Forced
      vital capacity, forced expiratory volume in 1 second, arterial oxygen tension,
      and arterial carbon dioxide tension improved significantly post-Tx. Actuarial
      survivals were 82%, 68%, and 63%, respectively, at 1, 3, and 7 years
      posttransplantation for emphysema patients vs 60%, 53%, and 42%, respectively, at
      1, 3, and 7 years posttransplantation for non-emphysema patients (P = .049).
      CONCLUSION: Lung transplantation in patients with emphysema offers good long-term
      survival, with significant improvement in functional status and low morbidity.
      The older age of emphysema patients was not associated with a higher incidence of
      postoperative complications.

PMID- 15866665
TI  - Basiliximab in lung transplantation: preliminary experience.
AB  - BACKGROUND: Basiliximab is a chimeric anti-interleukin-2 monoclonal antibody that
      has shown safety and efficacy in the prophylaxis of acute organ rejection in
      renal, liver, heart, and kidney-pancreas transplantation (Tx). The aim of this
      study was to present our initial experience with the use of Basiliximab in lung
      Tx. METHODS: Basiliximab (2 doses of 20 mg on day 0 and day 4) was administered
      to 16 patients treated with cyclosporine, azathioprine, and steroids between
      September 13, 2001 and August 26, 2003, including 12 men and 4 women patients
      with a mean age of 56.5 years (range, 19-69). The indication for use in
      transplantations were: reduced renal function (n = 14), post-Tx acute renal
      failure (n = 1) and steroid-resistant acute rejection (n = 1). Eight double-lung
      and eight single-lung Tx were performed for emphysema (n = 6), idiopathic
      pulmonary fibrosis (n = 7), silicosis (n = 2), and cystic fibrosis
      retransplantation (n = 1). RESULTS: The incidence of acute rejection was 16.6% (2
      patients). Infections included cytomegalovirus (CMV) 33.3% (n = 4), bacterial
      16.6% (n = 2), and fungal 8.3% (n = 1). Two patients died in the postoperative
      period and another at 3 months. There was no reaction to the medicine, and no
      malignancies or Bronchiolitis Obliterans Syndrome (BOS) during a follow-up period
      of more than 1 year in 10 patients. CONCLUSION: Basiliximab appeared to reduce
      the incidence of acute organ rejection and showed a good safety profile in terms
      of infections and adverse events.

PMID- 15866666
TI  - Respiratory disorders and quality of sleep in patients on the waiting list for
      lung transplantation.
AB  - BACKGROUND: The purpose of this study was to assess the quality of sleep and
      extent of respiratory disorders in patients awaiting lung transplantation as
      compared with a control group. METHODS: From September 2003 to November 2003, 17
      clinically stable patients on the waiting list for lung transplantation and 14
      healthy controls (with similar age, gender, and body mass index) were studied.
      Diagnostic polysomnography (PSG) was carried out for all subjects. RESULTS:
      Seventeen patients were included, 15 men and 2 women, aged 51 +/- 14 years. The
      indication for lung transplantation was emphysema in 7 cases, pulmonary fibrosis
      in 6, and "other" in 4. Patients awaiting lung transplantation had the following
      respiratory values: mean FEV1, 1105 mL (34% of predicted); PaO2, 54 mm Hg; and
      PaCO2, 44 mm Hg. Significant differences were found among the waiting-list
      patients in terms of predominance of light sleep, wakeful periods, and phase
      changes per sleep-hour, as compared with the control group. The recording of the
      respiratory events showed an apnea-hypopnea index of 6.13, sleeping time with
      SaO2 <90% of 1.80%, and a mean number of significant desaturations (<4%) of 6.38.
      There were no statistically significant differences with respect to the control
      group. CONCLUSIONS: Poor quality of sleep was observed in patients awaiting lung
      transplantation as compared with a healthy control group. There was no evidence
      of more respiratory events or significant desaturations in these patients,
      probably due to the provision of supplementary oxygen therapy during the PSG.

PMID- 15866667
TI  - Myocardial preservation using Celsior: clinical results in high-risk cardiac
      transplantation.
AB  - Graft failure during the first few days posttransplantation remains one of the
      main unresolved complications. The objective of this study was to evaluate the
      influence of Celsior preservation solution on the incidence of early graft
      failure in high-risk cardiac transplant recipients. A retrospective study was
      carried out evaluating the cardiac transplants in 179 heart recipients. The
      patients were divided into 2 groups: (1) Celsior preservation solution (n = 37),
      and (2) Control solution (n = 142). To evaluate the efficacy of the Celsior
      solution, a subgroup of transplants from older donors or with ischemia times
      greater than 4 hours was compared with the other cases. The incidence of early
      graft failure was lower among the Celsior subgroups with longer ischemia times or
      of older donors compared with the control groups. We conclude that preservation
      with Celsior solution in cardiac transplantation is safe and effective. It even
      has advantages to reduce early graft failure compared with conventional
      solutions, a benefit that may be more evident in subgroups at high risk for
      myocardial dysfunction.

PMID- 15866668
TI  - Sirolimus improves renal function in cardiac transplantation.
AB  - In kidney and liver transplantation, sirolimus therapy has been shown to be
      comparable to cyclosporine in a head-to-head comparison, but it results in better
      preservation of renal reserve. In heart transplantation, information about the
      use of sirolimus is limited. We present the results of the progressive conversion
      from cyclosporine to sirolimus in a series of 8 heart transplant patients in whom
      renal dysfunction developed. The baseline creatinine level was 2.4 +/- 0.5 mg/dL,
      and plasma levels of cyclosporine were within the therapeutic range. After the
      introduction of sirolimus, the creatinine level fell within the first month to
      1.76 +/- 0.2 mg/dL, or mean decrease of 0.6 +/- 0.25 mg/dL (P < .05). After 3 +/-
      2.2 months the improvement continued (1.69 +/- 0.2 mg/dL). In 1 patient sirolimus
      was withdrawn during the first 24 hours, because of gastric intolerance. No
      patient developed an opportunist infection, allograft rejection, or important
      hematologic disorder. We conclude that sirolimus appears to be effective in heart
      transplant patients to improve renal function.

PMID- 15866669
TI  - Comparative study of muromonab-CD3 (OKT3) versus daclizumab (Zenapax) in cardiac
      transplantation at our center.
AB  - Recent studies support the addition of new immunosuppressive drugs as cytolytic
      induction therapy in cardiac transplantation. We carried out a comparative study
      comprising 52 patients who had undergone cardiac transplantation at our center.
      Thirty patients received muromonab-CD3 (OKT3, Janssen-Cilag, The Netherlands) as
      the induction therapy, whereas 22 patients received Daclizumab (Zenapax, Hoffman
      La Roche, Nutley, NJ, USA) instead. All patients received cyclosporine or
      tacrolimus, mycophenolate, and steroids. Over an average follow-up period of
      23.21 +/- 18 months, we analyzed retrospectively the incidence of grade > or = 3A
      biopsy-confirmed acute rejection episodes, the presence of infectious processes
      at 1 and 6 months, the occurrence of significant secondary effects, and the
      necessity to modify the immunosuppressive therapy during the follow-up. The
      results suggest that daclizumab is linked to a decreased incidence of grade > or
      = 3A biopsy-confirmed acute rejection and to a reduced necessity to modify the
      immunosuppressive therapy during the medium-term follow-up.

PMID- 15866670
TI  - Use of oral sildenafil in patients with irreversible pulmonary hypertension not
      eligible for heart transplantation.
AB  - Heart transplantation is contraindicated in patients with acute irreversible
      pulmonary hypertension (PH), but new drugs are opening up therapeutic
      possibilities. Sildenafil citrate is a nonselective pulmonary vasodilator that is
      being used in our hospital to treat several patients with PH and which has
      allowed the inclusion of 1 patient on the waiting list for heart transplantation.
      A 20-year-old man with Becker muscular dystrophy was diagnosed at the age of 19
      years with dilated cardiomyopathy with severe pulmonary artery systolic pressure
      (PH = 60 mm Hg). A pretransplantation study, including a right hemodynamic
      analysis with an acute vasodilator test using intravenous epoprostenol, revealed
      the irreversible character of the PH. Inasmuch as the administration of
      dobutamine did not achieve an adequate reduction of PH, oral sildenafil was
      started (25 mg every 12 hours) as salvage therapy. An echocardiogram obtained 2
      months after starting sildenafil therapy showed normal right cavities, previously
      dilated, as well as minimal protosystolic tricuspid regurgitation without PH. A
      new right hemodynamic study performed after 4 months showed a reduction in
      pulmonary vascular resistance, from 8 U to 3.5 U Woods. As a result, the patient
      has now been included on the waiting list for heart transplantation. The
      promising example of this patient confirms the necessity to carry out controlled
      trials to establish definitively the indications for the use of sildenafil in
      patients with irreversible PH.

PMID- 15866671
TI  - Hemopoietic stem cell transplantation in childhood: reduction in mortality and
      improvement of survival over the years.
AB  - Stem cell transplantation (SCT) is an effective treatment for life-threatening
      hematologic and nonhematologic pediatric diseases. Reducing transplant-related
      mortality (TRM), a major complication of SCT, to improve long-term survival,
      therefore, is one of the main objectives of transplantation teams. We analyzed
      TRM and overall survival (OS) over the years in children undergoing SCT in our
      center. From June 1998 to October 2002, 156 consecutive children, 105 boys and 51
      girls, median age 10 years (range, 2-18), with different diagnoses underwent SCT
      (100 autologous and 56 allogeneic). OS and TRM were analyzed in 2 different
      periods (June 1989-December 1998 and January 1999-October 2002) and grouped
      according to the different SCT modalities. The median follow-up was 18 months
      (range, 1-160). Autologous TRM showed a statistically significant improvement
      within 1999-2002 (0%) compared with 1989-1998 (12.2%) (P < .05). There were no
      statistical differences for allogeneic SCT. OS was 34% in the first period and
      80.4% in the second period (P < .01), the improvement being for both autologous
      and allogeneic SCT. In our study, TRM decreased significantly for those children
      receiving autologous SCT in recent years. OS was significantly better in the
      latter period (1999-2002), both globally and for each SCT modality.

PMID- 15866672
TI  - Organ donation: a comparison of donating and nondonating families.
AB  - The family interview to determine the wishes of the deceased during life about
      organ donation is not only a legal requirement, it is also the stage at which
      most potential donors are lost. Minimizing these losses necessitates awareness of
      all the variables involved in the family interview so that, before starting the
      interview, one understands the important key points affecting the outcome. We
      showed that some variables among 268 interviews are susceptible to intervention:
      the information and treatment perceived by the family members during the hospital
      stay and the preparation of the interview, such that a suitable number of the
      closest members of the family with a decision capacity is always present. Other
      noncontrollable factors that are important in the final decision included the
      social and demographic level, the prosocial attitude of the deceased, and prior
      knowledge and opinions about organ donation. Informative events within the
      hospital to improve the predisposition and collaboration of health care
      professionals were key to improving the public's perception of organ donation and
      achieving greater confidence in health care centers and their staff. Furthermore,
      the family interview must be planned by the transplant coordinators to limit
      improvisation.

PMID- 15866673
TI  - Pancreas donation for islet transplantation.
AB  - Islet transplantation, though still in the experimental phase, is a therapeutic
      option that has opened new expectations for the control of diabetes mellitus.
      Initial results are encouraging for the significant advantages compared with
      whole pancreas transplantation for selected patients with type 1 diabetes
      mellitus, with or without kidney failure. However, the success of
      transplantation, both at centers with more experience and others with less, is
      limited by the difficulty in obtaining a suitable number of donors and by
      laboratory isolation techniques. Significant advances require changes in donor
      selection, perfusion, oxygenation, and transfer of the pancreas, and in the
      process of isolation, purification, and culture in the laboratory. Of the 32
      pancreases sent to the islet isolation laboratory from different hospitals in
      Andalusia, a viable percentage of islets was finally available in 19. However, in
      only 4 (18%) procedures were the preparations considered optimal for implantation
      in 2 recipients.

PMID- 15866675
TI  - ABO-incompatible liver transplantation: a new therapeutic option for patients
      with acute liver failure in Chile.
AB  - Different ways have been suggested to expand donor numbers for liver
      transplantation. Transplantation using ABO-incompatible hepatic grafts has
      recently been a controversial issue due to the high risk of hyperacute rejection
      mediated by preformed anti-ABO antibodies. We report three patients with acute
      liver failure who were transplanted with ABO-incompatible livers: A to O in two
      patients and A to B in one case. We used pre- and posttransplant total plasma
      exchange, splenectomy, and triple immunosuppression. All three patients are
      alive; one graft was lost, probably secondary to thrombotic microangiopathy with
      low isohemagglutinin titers of 1:8. One patient developed acute cellular
      rejection that was reversed with a bolus of methylprednisolone. No antibody
      mediated rejection occurred. Financial and infectious considerations have to be
      considered. In our series, the final liver transplantation cost was higher than
      average for acute liver failure. Plasmapheresis has the highest cost of all the
      additional procedures. ABO-incompatible liver transplantation, because of the
      splenectomy it requires, has been associated with more infections due to
      encapsulated organisms. However, with splenectomy in our three patients, none had
      infections due to these bacteria. In our country, we do not consider ABO
      incompatible liver transplantation as a first-line option, except for highly
      selected patients.

PMID- 15866676
TI  - Pediatric renal transplantation: 13 years of experience--report from the Chilean
      Cooperative Multicenter Group.
AB  - Between 1989 and 2002, 178 renal transplants were performed in 168 pediatric
      patients in Chile. The mean age was 10.9 +/- 3.7 years (range 1 to 17.9). End
      state renal disease etiologies were: congenital renal hypoplasia/dysplasia,
      chronic glomerulonephritis, and reflux nephropathy. Seventy received a graft from
      a living donor (LD), and 108 from a cadaveric donor (CD). Only 9% received
      antibody induction. Acute rejection episodes were reported in 76 patients: 38% in
      LD recipients and 48% in CD recipients (P = NS). One-, 3-, and 5-year graft
      survivals were 88%, 84%, and 76%, respectively, for LD and 86%, 79%, and 68% for
      CD recipients. Actuarial graft survival was significantly better among those
      patients with serum creatinine < 1 mg/dL at 1 year posttransplant compared with
      those with creatinine > 1 mg/dL (P < .05). The graft survival rate has improved
      from the first period (1989 to 1996) to the second period (1997 to 2002); (P =
      .05). Patient survival rates at 1, 3, and 5 years were 98%, 98%, and 98%,
      respectively, for LD, and 95%, 94%, and 94% for CD. Global height/age Z-score
      decreased from -0.7 at birth to -1.5 when dialysis started, and to -2.4 at the
      time of transplantation. The Z-score height/age at 1, 3, and 5 years
      posttransplantation was -2.25, -2.24, and -2.5. No significant differences were
      observed in transplant outcomes comparing patients younger than 7 years with
      those older ones. In conclusion, pediatric renal transplant has been performed in
      Chile with acceptable morbidity. The patient and graft survivals are similar to
      the reported international experience. In the last period there was a significant
      improvement in graft survival.

PMID- 15866677
TI  - Hepatotoxicity associated with cyclosporine monitoring using C2 recommendations
      in adults renal recipients receiving ketoconazole.
AB  - Following the change, in the way we monitored cyclosporine (CsA) levels in
      January 2000 namely from C0 to C2 concentrations, in renal "de novo" allograft
      recipients, some patients treated with concomitant ketoconazole experienced liver
      toxicity, a complication that had not been previously seen with CsA monitoring
      using C0. Therefore, we decided to compare the outcomes of patients transplanted
      using CsA levels monitored by C0 (1998 to 1999) who also had simultaneous C2
      determinations (group A) with those of recipients transplanted after 2000 (group
      B). All received steroids, azathioprine, and CsA plus ketoconazole. Recipients
      were followed for at least a year after transplantation. Patients in group B
      showed higher CsA C2 levels, AUC concentrations, and drug doses during the
      immediate postsurgical period, and at 2 weeks as well as 4 and 6 months
      posttransplantation. Six group B patients (26%) but no group A recipients
      displayed, severe liver toxicity characterized by jaundice, elevated liver
      enzymes, with negative serological tests for CMV, HVC, and HVB. There was a
      correlation between the GOT and the C2 CsA levels; both normalized 15 to 55 days
      after CsA dose reduction. High C2 CsA levels, which have been recommended when
      the drug is used alone in renal transplantation, cannot be used in patients
      taking ketoconazole, because C2 neither represents nor correlates with AUC drug
      exposure. Thus high C2 levels may produce liver toxicity.

PMID- 15866678
TI  - Impact of pregnancy on the function of transplanted kidneys.
AB  - INTRODUCTION: This study reviewed the course of pregnancies in terms of impact on
      renal function and delivery-related data among women who received kidney
      transplants in our unit. METHODS: We reviewed the medical records of women
      transplanted between 1982 and 2002 who became pregnant. We recorded the data of
      medical, obstetrical, and transplant-related complications, plasma creatinine
      levels, and blood pressures at baseline, delivery, and 12 months after delivery.
      RESULTS: Thirty women had 37 pregnancies. Immunosuppressive protocols included
      cyclosporine, ketoconazole, azathioprine, and prednisone in 22 patients or
      azathioprine and prednisone in 15. Renal function decreased significantly: mean
      creatinine levels at baseline, delivery, and after 1 year were: 1.19 +/- 0.38
      mg/dL; 1.44 +/- 0.70 mg/dL; and 1.38 +/- 0.53 mg/dL, respectively (P = .023 and P
      = .004 vs baseline respectively). Systolic and diastolic blood pressures at
      delivery were higher than at baseline (134 +/- 19 and 86 +/- 14 mm Hg vs 126 +/-
      21 and 79 +/- 13 mm Hg (P = .029 and P = .053, respectively). These values
      normalized 1 year later (128 +/- 21 and 80 +/- 16). Decreased use of
      antihypertensive drugs were the cause of poor blood pressure control (1.8 +/- 1.3
      vs 0.9 +/- 0.7, P < .01). Blood pressure control improved following delivery. The
      most frequent complications were preeclampsia (18.9%), intrahepatic cholestasis
      (13.5%), and urinary tract infections (13.5%). There were five rejection
      episodes. Seven miscarriages took place and one mole. Eleven pregnancies were
      uncomplicated. CONCLUSION: Renal transplantation is the best treatment for
      fertile women with end-stage renal disease who want to become pregnant. However,
      pregnancy is risky for the mother, fetus, newborn, and allograft.

PMID- 15866679
TI  - Correlation Between C2 and AUC(0-4) in Renal Transplant Patients Treated With
      Diltiazem.
AB  - BACKGROUND: The area-under-the-curve (AUC) of cyclosporine (CsA) reflects
      exposure to the drug, but this monitoring strategy is time-consuming and not cost
      effective. Recently, it has been suggested that the concentration at 2 hours
      after dosing (C2) shows the best correlation with AUC. The C2 has been replacing
      the trough measurement (C0) to monitor CsA therapy, but in patients receiving
      diltiazem there is not much information about this issue. We investigated the
      correlations between C2 and C0 with absorption AUC over the first 4 hours (AUC(0
      4)) in renal stable transplant patients receiving CsA therapy with or without
      diltiazem. PATIENTS AND METHODS: Ten patients (five men) of ages 23 to 68 years
      and 6 to 84 months after transplantation, were randomly assigned to an 8-week
      initial period of either diltiazem washout or controlled treatment with
      diltiazem. Time-concentration curves of cyclosporine were performed at the end of
      this period using a specific RIA measurement of blood samples. Thereafter, a
      crossover of the groups was performed and after another 8 weeks, a second curve
      was obtained. Drugs that change the pharmacokinetics of cyclosporine or diltiazem
      were not allowed. RESULTS: The cyclosporine daily dose was lower with diltiazem
      (173 +/- 4 mg vs 213 +/- 4 mg, P = .002), but despite a dose reduction of only
      19% +/- 1.5%, there was a trend to a larger AUC/dose (28 +/- 5 ng x h/mL x mg vs
      17 +/- 2 ng x h/mL x mg, P = .1) and a trend to an increased C2 when treatment
      included diltiazem (1035 +/- 156 ng/mL vs 652 +/- 126 ng/mL, P = NS). Moreover,
      we confirmed that C2 showed the best correlation with AUC(0-4), (r = 0.7, P =
      .04), a correlation that improved with diltiazem (r = 0.9, P < .002). CONCLUSION:
      C2 is the point that correlates best with AUC(0-4) with or without diltiazem. C2
      in the presence of diltiazem was associated with a stronger, more significant
      correlation with AUC(0-4).

PMID- 15866680
TI  - C2 monitoring of cyclosporine in stable renal transplant patients results in
      lower costs and improved renal function.
AB  - INTRODUCTION: C2 (2-hour post-absorption levels) monitoring of cyclosporine (CsA)
      seems to reduce the rate of acute rejection episodes (ARE) without increasing
      nephrotoxicity during the first months after transplant. There are a few reports
      on the impact of adopting this strategy in patients with stable renal
      transplants. We herein report a prospective trial in long-term renal transplant
      patients (>6 months) monitored by C0 or C3 who were switched to C2 monitoring.
      METHODS: Seventy-six (mean age = 43 +/- 11 years) kidney transplant patients
      (mean = 37 +/- 21 months after transplant) receiving CsA, steroids, and
      azathioprine were switched to C2 monitoring, seeking to achieve a target range of
      800 +/- 100 ng/mL. The patients were followed for at least 6 months. RESULTS: At
      conversion the C2 values of 61% of the patients were above and 17% below the
      therapeutic range. Six months after conversion there was a significant reduction
      in BUN (29 +/- 11 vs 27 +/- 10, P < .01), Creatinine (Cr), cholesterol, and
      triglyceride levels were unchanged. Mean CsA dose was decreased 10% from 244 +/-
      63 to 220 +/- 52 (P < .01), implying a net savings of 390 US dollars per patient
      per year. Among the group of patients who showed a high C2 level, there was also
      a reduction in BUN (30 +/- 12 vs 27 +/- 10, P < .01) and a nonsignificant
      decrease in Cr (1.53 +/- 0.6 vs 1.50 +/- 0.6). CONCLUSIONS: C2 monitoring in
      stable kidney transplant recipients is feasible and safe. The strategy results in
      reduced drug costs and improved renal function.

PMID- 15866681
TI  - Valsartan-induced hematocrit changes in renal transplant patients.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II
      receptor type 1 blockers (ARB) are frequently prescribed for renal transplant
      patients. The main reasons for their use are that their antihypertensive and
      antifibrogenic effects may prevent chronic renal allograft dysfunction,
      potentially improving transplant survival. Furthermore, ACE and ARB have been
      used to reduce the hematocrit in patients with posttransplant erythrocytosis. We
      evaluated the effects of the ARB valsartan on the evolution of hematocrit in
      stable renal transplant patients treated with cyclosporine (CsA), azathioprine
      (Aza), and prednisone. PATIENTS AND METHODS: Twenty-six stable renal transplant
      patients treated with valsartan 80 mg/d orally were followed for 6 months.
      Evaluations were performed prior to as well as at 3 and 6 months following the
      initiation of valsartan. RESULTS: The hematocrit levels decreased significantly
      at 3 months (46.1 +/- 7.3 vs 39.9 +/- 5.8 ; P < .0001) in patients with a normal
      hematocrit, namely a level over 38%, with no further reduction at 6 months. In
      recipients with an hematocrit less than 38%, there was no significant reduction,
      either at 3 or 6 months follow-up. Valsartan was well tolerated without
      significant side effects. CONCLUSION: We postulate that inhibition of the
      proerythropoietic effects of angiotensin II and/or the reduction in hypoxia
      within the renal tubulointerstitium as well as the vasodilator effects on the
      efferent arterioles, represent possible mechanisms for the reduction and
      stabilization of the hematocrit in stable renal transplant patients.

PMID- 15866683
TI  - Cyclosporine-based immunosuppressive strategies for kidney recipients: interim
      analysis of German data from the Multinational Observational Study (MOST).
AB  - INTRODUCTION: We collected data from kidney recipients with a functioning graft
      at German kidney transplant centers in order to analyze the efficacy of various
      cyclosporine (CsA)-based immunosuppressive strategies, the effects of different
      perioperative and maintenance regimens, and the impact of donor source on
      clinical outcome. METHODS: As part of the ongoing prospective Multinational
      Observational Study in Transplantation (MOST), data for both prospective and
      retrospective analysis were collected from kidney recipients over 18 years
      bearing a functioning graft that was transplanted at 21 German kidney transplant
      centers between 1987 and 2002. RESULTS: Data from 1223 renal graft recipients,
      including their CsA-based immunosuppressive regimens, were stratified as: 402 de
      novo patients (median 6.8 months posttransplant) and 821 patients on maintenance
      therapy (median 71 months posttransplant). Triple regimens with CsA +
      mycophenolate mofetil (MMF) + steroids (Ste) currently comprise the major
      perioperative immunosuppressive strategies in Germany (de novo 65%). IL-2
      receptor antagonist (IL-2Ra) use is increasing (de novo 18%, maintenance 4%),
      while mono and dual regimen use de novo is declining (de novo 4%, maintenance
      20%). Among 689 patients transplanted between 1987 and 2002 with outcome data,
      the mean incidence of acute rejection during the first posttransplant year was
      21.6%. Rejection rates on initial therapy with CsA + MMF + Ste +/- antibodies (n
      = 517) averaged 17.8%. CONCLUSIONS: Between 1987 and 2002, CsA-based
      immunosuppression combined with MMF and Ste became the most commonly used
      strategy for both initial and maintenance therapy after kidney transplantation in
      Germany, yielding the low acute rejection rates particularly when combined with
      IL-2Ra.

PMID- 15866684
TI  - Graft function, cardiovascular risk factors, and sex hormones in renal transplant
      recipients on an immunosuppressive regimen of everolimus, reduced dose of
      cyclosporine, and basiliximab.
AB  - A prospective, randomized trial evaluated the combination of everolimus of 1.5 or
      3 mg/d with steroids, basiliximab, and low-dose cyclosporine (CsA) adjusted by C2
      monitoring in 256 renal transplant recipients. CsA C2 target levels, initially
      set at 600 ng/mL, were tapered over time posttransplant. The median serum
      creatinine concentrations were 130 mumol/L in both sirolimus groups (1.5 and 3
      mg/d) at 6 months. Biopsy-proven acute rejection (BPAR) occurred in 13.7% and
      15.1% of patients in the 1.5 and 3 mg/d groups, respectively. The incidence of
      BPAR was significantly higher among patients with everolimus trough levels < 3
      ng/mL. Posttransplant diabetes mellitus occurred rarely, and blood pressure
      control appeared favorable; however, serum cholesterol levels were increased by
      approximately 50%, and serum triglycerides by approximately 100%. Serum
      testosterone concentrations increased after renal transplantation in both
      everolimus groups. Concentration-controlled everolimus therapy combined with low
      dose CsA provides effective protection against rejection with good renal function
      and safety profiles.

PMID- 15866685
TI  - Relationship between donor factors, immunogenic up-regulation, and outcome after
      kidney transplantation.
AB  - Epidemiological data show that the cause of brain death as well as the condition
      of the organ donor have considerable influence on the outcome of kidney
      transplantation. An early immunogenic up-regulation, which already exists at the
      time of organ removal seems to be primarily responsible. So far it has remained
      unclear which donor factors cause this effect. In a prospective study of 37 organ
      donors a 0-hour biopsy was performed at the time of explantation to measure the
      expression of HLA-DR and endothelin-1 (ET-1) immunohistologically using the
      alkaline phosphatase anti-alkaline phosphatase (APAAP) method. The transplant
      outcome and the immunohistological results were correlated with various donor
      factors. Statistically significant correlations were seen with the following
      parameters: the donor serum creatinine prior to explantation correlated with the
      incidence of delayed graft function (DGF: 104 +/- 39 vs 78 +/- 35 micromol/L
      versus no DGF n = 37; P = .043). Early graft loss after transplantation
      correlated significantly with increased numbers of leukocytes as well as with
      decreased O2 saturation in the donor immediately before explantation (leucocytes:
      16.7 +/- 6.8 vs 12.6 +/- 4.6/nL, n = 37; P = .036; O2 saturation: 94.1% +/- 6.9%,
      vs 97.7% +/- 2.3%, n = 37; P = .026). Further, donor-independent factors that
      correlated with acute rejections included cold ischemic time (P = .031), HLA
      mismatches (P = .028), and occurrence of DGF (P = .033). The degree of HLA-DR
      expression (range 0 to 2) correlated significantly with early graft loss (2.0 +/-
      0.2 vs 1.33 +/- 0.9 for graft function, n = 37; P = .01) as well as the ET-1
      expression with DGF (2.0 +/- 0.3 vs 1.5 +/- 0.7 versus no DGF, n = 37; P = .016).
      In summary, marginal donors should be seen as high immunological risk situations
      that need careful conditioning.

PMID- 15866686
TI  - Two-hour postdose concentration: a reliable marker for cyclosporine exposure in
      adolescents with stable renal transplants.
AB  - In pediatric renal transplant recipients, most patients receive maintenance
      treatment with cyclosporine (CsA) and mycophenolate mofetil (MMF). Until now, the
      2-hour postdose CsA target level for combined maintenance treatment with MMF has
      not been defined. This prospective pilot study evaluated the pharmacokinetics of
      CsA under the influence of MMF to determine a reliable single CsA concentration
      time that correlates with the area under the curve (AUC(0-6h)) estimates for
      adolescents who were additionally treated with MMF during the late posttransplant
      period. The study included 13 adolescents (mean posttransplantation time, 3.5 +/-
      2.55 years) with stable renal transplant function (S-Crea 121 +/- 40 micromol/L).
      CsA pharmacokinetic absorption profiles over a 6-hour dose interval (n = 26) were
      evaluated for the optimal single peak concentration using the CsA concentrations
      predose (C0) and at 1, 2, 3, 4, and 6 hours postdose (C1-6). Whereas C2 (mean
      743.2 +/- 221.8 ng/mL) was the single point with the closest correlation to AUC(0
      6h) (r2 = 0.86; P < .001), C0 (mean 120.5 +/- 35.2 ng/mL) showed the weakest
      correlation (r2 = 0.61, P = .002). C2 appears to be an accurate predictor of CsA
      exposure in adolescent kidney transplant recipients under maintenance
      immunosuppression in combination with MMF. Average values achieved with current
      dosing practices cluster around the target C2 ranges recommended for adults. The
      data provide a foundation for initiation of prospective clinical trials to assess
      the long-term risk for chronic allograft dysfunction among pediatric stable renal
      transplant patients in combination protocols.

PMID- 15866687
TI  - Cyclosporine C2 levels in de novo renal allograft recipients: a German
      multicenter prospective observational study.
AB  - This ongoing multicenter prospective observational study was undertaken in de
      novo renal allograft recipients managed with cyclosporine (CsA) trough (C0) and 2
      hour postdose (C2) level monitoring at defined times so as to assess the risk for
      an acute rejection episode or allograft dysfunction. The renal transplant
      recipients (n = 159) were enrolled at 11 German centers. The 6-month
      posttransplant data from 138 patients were evaluable for this interim analysis.
      Mean C2 levels (ng/mL), which were measured by liquid chromatography-tandem mass
      spectrometry at a central laboratory, were: days 3 to 5: 873.1 +/- 391.9; days 7
      to 10: 939.1 +/- 422.8; days 14 to 28: 1116.3 +/- 497.6; 3 months: 905.0 +/-
      316.8; and after 6 months: 787.0 +/- 276.5. To identify patients at higher risk
      for acute rejection or allograft dysfunction, we calculated the relative CsA
      absorption capacity (C2 [ng/mL]/morning dose [mg/kg]; CsA-Abs), yielding mean
      values on days 3 to 5: 284.4 +/- 115.1; days 7 to 10: 306.7 +/- 134.8; days 14 to
      28: 382.5 +/- 164.7; month 3: 501.5 +/- 168.8; month 6: 512.7 +/- 176.5. Three
      groups were distinguished by CsA-Abs at days 7 to 10: low absorbers (CsA-Abs <
      200), normal absorbers (CsA-Abs 200 to 350), and high absorbers (CsA-Abs > 350).
      A between-group comparison of absorption level at 6 months posttransplant
      revealed the incidences of biopsy-proven acute rejection and Cockcroft-Gault
      formula-based mean glomerular filtration rates of 23.8% and 54.7 +/- 19.0 mL/min,
      22.6% and 59.5 +/- 20.7 mL/min, and 17.6% and 67.7 +/- 23.5, respectively. In
      conclusion, mean C2 levels >1000 ng/mL are attained within 2 to 4 weeks, with CsA
      Abs increasing continuously over the first 6 posttransplant months. High CsA
      absorbers show a propensity toward good allograft function and lower acute
      rejection rates at 6 months after renal transplantation.

PMID- 15866688
TI  - Living donor kidney transplantation: impact of differentiated immunosuppressive
      regimen.
AB  - INTRODUCTION: Recipients of related (R) and unrelated (NR) living donor kidney
      transplantations (LDKTX) receive immunosuppressive (IS) therapy 5 days in advance
      in order to achieve low rates of acute rejection episodes. We herein report the
      different IS regimens for R and NR transplants as well as acute rejection and
      primary function rates. METHODS: Ninety-five LDKTX (69% R, 31% NR) were performed
      with mean cold ischemia time (CIT) of 145 +/- 32 minutes. In R-LDKTX mean age of
      recipients was 31 +/- 12.5 years. This cohort included 41 men and 25 women whose
      mean age was 50 +/- 11.1 years. The therapeutic regimen for R-LDKTX included
      CyA/MMF/prednisone; for NR-LDKTX, FK/MMF/prednisone. Among the recipients of NR
      grafts the mean recipient age was 51 +/- 8.5 years. This cohort included 23 men
      and 6 women whose donor mean age was 50 +/- 8.8 years. The mean HLA mismatch
      among R-LDKTX (2.3) was significantly less than that in the NR-LDKTX cohort
      (3.51). RESULTS: At a mean follow-up of 35 months, 94.7% of grafts were
      functioning. DGF was seen in only one recipient (1%). Three grafts were lost due
      to acute (R) or chronic (NR) rejection or to multiorgan failures. Two recipients
      died with functioning grafts. Biopsy-proven rejection episodes were observed in
      17.2% of NR-LDKTX and 9% of R-LDKTX. In R-LDKTX 50% of rejection episodes were
      corticoid-sensitive, while 33% needed ATG, and 16% were treated by a switch to
      FK. In NR-LDKTX 20% of rejections were corticoid-sensitive, 40% needed ATG, and
      40% were treated with rapamycin rescue therapy. CONCLUSION: Although HLA
      mismatching is significantly different between R- and NR-LDKTX, no difference in
      outcome was observed, which may be due to the specific therapeutic regimen and
      short CIT.

PMID- 15866689
TI  - Changes in quality of life after renal transplantation.
AB  - Quality of life is becoming an increasingly important concept in the evaluation
      of different therapeutic interventions. In this cross-sectional study, quality of
      life analyzed in 76 renal transplant patients was compared with 65 patients with
      end-stage renal disease (ESRD) awaiting transplantation. Both groups were asked
      to estimate their subjective quality of life by responding to a multidimensional
      questionnaire that sought information in the following areas: (1)
      sociodemographic data, (2) a personality test (Giessen-Test), (3) information
      about employment, (4) assessment of anxiety and depression (GHQ-28), (5) the SF
      36 as an important measurement for quality of life, and (6) the ESRD symptom
      checklist-transplantation module. The sociodemographic profiles of both groups
      were similar. The SF-36 revealed significantly higher values for transplant
      recipients in terms of physical functioning (P < or = .001), general health
      perceptions (P < or = .01), social functioning (P < or = .01), and physical
      summary value (P < or = .001). The other tests (Giessen-Test and GHQ-28) and
      employment data showed no significant differences between the two samples.
      Collectively, the data demonstrate a considerable improvement in quality of life
      in renal transplant patients. Despite good physical recovery and higher quality
      of life after transplantation, the rate of vocational rehabilitation remained
      low, partially explained by the currently high levels of unemployment.

PMID- 15866690
TI  - Laparoscopic organ retrieval for living donor liver transplantation does not
      prevent graft injury.
AB  - The cause of transplant failure may be difficult to define. However, organ
      retrieval before preservation and transplantation is an important factor. Organ
      manipulation during harvesting, which is inevitable with most techniques, leads
      to injury upon reperfusion including microcirculatory disturbances. Recently,
      laparoscopic organ retrieval has been successfully performed for human living
      donor liver transplantation (LDLT). Pneumoperitoneum for laparoscopy changes the
      pattern of hepatic blood flow. To study the effects of pneumoperitoneum on the
      graft prior to cold storage, livers from Sprague-Dawley rats underwent
      pneumoperitoneum with an intra-abdominal pressure of 8 mm Hg for 90 minutes.
      Subsequently, intravital microscopy was performed to assess intrahepatic
      microcirculation and transaminases were measured. Serum transaminases increased
      1.5-fold compared with sham controls (P < .05). Intrahepatic microcirculation was
      significantly disturbed immediately after pneumoperitoneum. If this is confirmed
      in humans, laparoscopic organ retrieval for LDLT would be expected to decrease
      graft quality and not be beneficial in liver transplantation.

PMID- 15866691
TI  - Acute liver failure: from bench to bedside.
AB  - Acute liver failure constitutes a challenge to clinicians and scientists alike.
      The course of the disease, usually unpredictable and polarizing, is associated
      with a high mortality unless liver transplantation is feasible, but can end in a
      spontaneous restitution. It poses many scientific questions regarding the
      mechanisms of liver cell damage and regeneration and the possibility of new
      therapeutic approaches. However, the performance of clinical studies in patients
      in acute liver failure presents problems because of the varied etiology, the
      small number of cases, and furthermore due to ethical and logistical
      difficulties. For this reason experimental investigations have gained a special
      importance. Arising from the improved understanding of the mechanisms of liver
      cell damage in acute liver failure, which may be primarily due not to the initial
      noxious agent alone but may also be triggered secondarily by the release of
      proinflammatory mediators, there are numerous options for liver cell protection,
      some of which have already proved successful in experimental studies. New
      insights into the mechanisms of regulation of liver regeneration and the
      physiological liver mass, gathered in particular from experimental models of
      partial hepatectomy and by the use of gene-manipulated animals, have contributed
      to the development of new therapeutic approaches for the stimulation of liver
      cell regeneration. Temporary liver support systems have already been successfully
      employed in some cases under clinical conditions. Although the systematic
      experimental investigation of many of the questions of acute liver failure has
      significantly contributed to a better understanding of liver cell damage and
      regeneration, the application of this new knowledge to clinical practice is to
      some extent made difficult by the artificial simplification that experimental
      studies inevitably entail and needs to be validated by controlled clinical
      studies.

PMID- 15866692
TI  - Protective effect of endotoxin preconditioning in pancreas: analysis with DNA
      chip arrays.
AB  - Recently we demonstrated a protective effect of endotoxin preconditioning 24
      hours before pancreatic ischemia-reperfusion injury, which has also been
      described for other organs. The mechanisms underlying this phenomenon, such as
      differential gene expression, are poorly investigated. We chose to approach this
      question by investigating differential gene expression in the rat pancreas over
      the time course of endotoxin pretreatment. Male Wistar rats (5 groups, 5 animals
      per group) were pretreated with endotoxin intraperitoneally (1 mg/kg of body
      weight). After treatment at 30 minutes, and at 3 and 24 hours the pancreas was
      removed. Untreated animals and animals with injection of saline solution served
      as controls. After RNA isolation, RNA was pooled and hybridized to Affymetrix
      chips to measure the relative mRNA levels of 7000 genes and 1000 expression
      sequence tags. Three hours after administration of endotoxin there was an
      activation of proinflammatory transcription factors and other proinflammatory
      genes. After 24 hours there was a clear decrease of these proinflammatory genes,
      but a remaining and increasing upregulation of important antiapoptotic genes,
      antiproteases, and other probably protective genes. There was also a significant
      upregulation of complement factors. It was surprising that heat-shock proteins
      and other typical immediate early genes of the AP-1 complex were not upregulated.
      Our data show that 24 hours after endotoxin stress there is a regulation of a
      network of genes that represents a multifaceted preconditioning. As most
      important factors, inhibition of apoptosis and antiproteatic strategies are
      identified. Heat-shock proteins seem to play no important role in the mechanism
      of endotoxin preconditioning.

PMID- 15866693
TI  - Anti-TNF-alpha therapy for acute rejection in intestinal transplantation.
AB  - INTRODUCTION: We present our experience with infliximab rescue therapy for
      steroid- and OKT3-resistant rejection after intestinal transplantation (ITx).
      METHODS: Twelve ITx and one multivisceral transplant recipients were
      immunosuppressed with tacrolimus, rapamycin, daclizumab, steroids (n = 10) or
      tacrolimus, campath, and steroids (n = 3). RESULTS: In two patients, severe acute
      rejection did not resolve despite steroid bolus therapy plus 5 to 10 days of OKT3
      treatment. Signs of moderate rejection persisted in the distal portions of the
      grafts. Treatment with infliximab, a chimeric anti-TNF-alpha antibody (four
      infusions of 3 mg/kg body weight), induced a complete remission of histological
      and clinical signs of rejection. Two further patients with steroid-resistant
      rejection received two courses of infliximab (3 mg/kg body weight) as
      antirejection therapy. All rejection episodes resolved completely. CONCLUSIONS:
      Infliximab effectively treats steroid and OKT3 resistant acute rejection episodes
      of intestinal transplantations.

PMID- 15866695
TI  - Humoral theory of transplantation: mechanism, prevention, and treatment.
AB  - We discuss the potential mechanisms of antibody-induced primary endothelium
      injury, which includes complement-dependent pathway (membrane attack complex
      formation, recruitment of inflammatory cells, and complement-complement receptor
      mediated phagocytosis) and complement independent pathway antibody-dependent cell
      cytotoxicity. Secondary to endothelium injury, the following pathological
      reactions are found to be responsible for progressive tissue injury and final
      graft function loss: platelet activation and thrombosis, pathological smooth
      muscle and endothelial cell proliferation, and humoral and/or cellular infiltrate
      mediated parenchyma damage after endothelium injury. We also introduce three
      categories of therapeutic strategy in the prevention and treatment of antibody
      mediated rejection: (1) inhibition and depletion of antibody producing cells
      (immunosuppressants, antilymphocyte antibodies, splenectomy); (2) removal or
      blockage of preexisting or newly developed antibodies (immunoadsorption,
      plasmapheresis/plasma exchange, intravenous immunoglobulin); and (3) impediment
      or postponement of antibody-mediated primary and secondary tissue injury
      (anticoagulation, glucosteroids). In conclusion, because alloantibodies have
      destructive effect on allografts, alloantibody monitoring becomes extremely
      important. It will help clinicians to determine a patient's humoral responses
      against allograft and will therefore direct clinicians to optimize and/or
      minimize immunosuppressive drug therapy.

PMID- 15866696
TI  - Preformed cytotoxic antibodies in potential allograft recipients: recent data.
AB  - Presensitization to donor human leukocyte antigen (HLA) remains a major barrier
      to cell and organ transplantation, thereby contributing to patient mortality. The
      risks associated with transplantation in the presence of preformed antidonor HLA
      antibodies range from hyperacute rejection and increased frequency and severity
      of rejection to no appreciable effect on transplant outcome. Recent evidence has
      emphasized the importance of immunologic history, anti-HLA antibody class and
      titer, and differential organ susceptibility to antibody-mediated damage to
      explain differences in risk for antibody-mediated rejection. Furthermore, in
      studies of endothelial cells, ligation of class I molecules by subsaturating
      concentrations of antibodies stimulated expression of cell survival proteins,
      raising the possibility that, under certain conditions, antibodies promote graft
      accommodation providing a mechanism for the endothelium to resist immune and
      inflammatory damage. The discovery of capillary-bound C4d as a robust diagnostic
      marker for antibody-mediated rejection, coupled with the development of solid
      phase assays for the identification of HLA-specific antibodies, has enhanced our
      ability to detect antibody-mediated rejection and interpret cross-match results.
      With new diagnostic tools and immunosuppression regimens such as plasmapheresis
      and intravenous immunoglobulin therapy targeting the humoral immune response, it
      is time for a concerted effort to reassess the role of alloantibodies in acute
      and chronic rejection.

PMID- 15866697
TI  - Intravenous immunoglobulin and plasmapheresis in acute humoral rejection:
      experience in renal allograft transplantation.
AB  - Acute humoral rejection (AHR) in kidney transplantation is associated with higher
      rates of allograft loss when compared with acute cellular rejection (ACR).
      Treatment with intravenous immunoglobulin (IVIG) combined with plasmapheresis
      (PP) has been used recently in many centers. We report the incidence, clinical
      characteristics, and outcome of patients with AHR treated with IVIG and PP. All
      patients (n=519) at our institution who underwent kidney transplantation between
      January 1999 and August 2003 were retrospectively analyzed and classified
      according to biopsy results into three groups: AHR, ACR, and no rejection. AHR
      was diagnosed in 23 patients (4.5%) and ACR in 75 patients (15%). Mean follow-up
      was 844+/-23 days. Female sex, black race, and high panel-reactive antibody were
      risk factors for AHR. Most AHR patients (22 of 23) were treated with IVIG and PP.
      Two-year graft survival was numerically worse in patients with AHR versus ACR
      (78% vs. 85%, p=0.5) but the difference was not statistically significant. Graft
      survival after AHR treated with IVIG and PP is much better than it has been
      historically. IVIG in combination with PP is an effective treatment for AHR.
      Graft survival in this setting is similar to graft survival in patients with ACR.

PMID- 15866698
TI  - Intravenous immunoglobulin induction treatment in flow cytometry cross-match
      positive kidney transplant recipients.
AB  - Many recent studies have demonstrated increased acute humoral, cellular,
      subclinical, or chronic rejection, and decreased allograft survival in flow
      cytometry cross-match-positive kidney transplant recipients. The use of newer
      techniques and more sensitive of enzyme-linked immunosorbent assay (ELISA) or
      Flow Beads (microparticle based methods), donor-specific anti-human leukocyte
      antigen (HLA) antibodies have been detected in these immunologically high-risk
      patients. Intravenous immunoglobulin (IVIG) has immunomodulatory effects and has
      been demonstrated to downregulate anti-HLA antibodies in highly sensitized
      dialysis patients awaiting transplantation. Our initial studies demonstrate that
      IVIG induction treatment is promising in flow cytometry cross-match-positive
      kidney transplant recipients, and thus, those patients should not be excluded
      from receiving transplantation despite a positive flow cytometry cross match.
      Further studies with long-term follow-up are required to determine the effective
      dose and duration of IVIG treatment, and additional studies are needed to
      determine the most accurate tests for risk stratification.

PMID- 15866699
TI  - Factors associated with and predictive of persistence of donor-specific antibody
      after treatment with plasmapheresis and intravenous immunoglobulin.
AB  - Antibody to donor HLA antigens is a significant barrier to both access to and
      outcome of allogeneic transplants. Many attempts have been made to desensitize
      patients with HLA-specific antibody, but the most effective and durable have been
      treatment with high-dose pooled human intravenous immunoglobulin (IVIg) and a
      combination of plasmapheresis and low-dose IVIg. Despite the success of these
      treatments, low levels of donor-specific antibody (DSA) persist in some patients.
      We examined factors that may be related to and used to predict the elimination of
      DSA. The most significant associations have been strength of antibody at
      initiation of treatment and antibody specificity, although other factors revealed
      a trend toward association. We demonstrate how the types of data generated here
      can be used to predict elimination or persistence of DSA.

PMID- 15866700
TI  - Effect of delayed graft function in hypersensitized kidney transplant recipients.
AB  - There is increased evidence about the deleterious effect of delayed graft
      function (DGF) in both short- and long-term kidney graft outcome. Among the
      mechanisms involved in the production of DGF, immune factors play a role,
      especially in the level of hypersensitization. From the 1389 patients
      transplanted at our hospital until November 2004, it has been found that the
      presence of moderate and high levels of sensitization, as measured by panel
      reactive antibodies, is a risk factor for suffering from DGF. Further, DGF was
      associated with poor graft survival, and the risk was even higher when DGF was
      combined with moderate/high panel-reactive antibodies. Recent data demonstrate
      the usefulness of intravenous immunoglobulins in the management of
      hypersensitized patients in terms of short-term outcome. It remains to be
      demonstrated whether this therapy is able to ameliorate the higher ischemic
      injury that kidneys undergo from these immunologically high-risk patients.

PMID- 15866701
TI  - Utility of peritransplant and rescue intravenous immunoglobulin and
      extracorporeal immunoadsorption in lung transplant recipients sensitized to HLA
      antigens.
AB  - The role of anti-human leukocyte antigen (HLA) antibodies in lung transplantation
      is not fully clear. The presence of pretransplant third-party anti-HLA antibodies
      or the development of de novo anti-HLA antibodies has been associated with acute
      posttransplant complications, bronchiolitis obliterans syndrome (BOS), and early
      mortality in some studies. However, little has been reported regarding the
      utility of desensitization therapy in sensitized lung transplant recipients. For
      approximately 3 years, desensitization therapy consisting of intravenous
      immunoglobulin (IVIG) and, in most instances, extracorporeal immunoadsorption
      (ECI) has been administered peritransplant to lung transplant recipients at our
      institution with third-party anti-HLA antibodies or as rescue therapy to those
      who develop de novo anti-HLA antibodies. Notably, the administration of
      peritransplant desensitization therapy to these patients has been associated with
      improvement in several clinical parameters, including acute rejection and BOS.
      Furthermore, administration of rescue IVIG with or without ECI has been
      associated with an overall improvement in the rate of pulmonary function decline.
      Our experience suggests that desensitization therapy may be beneficial for lung
      transplant recipients with pretransplant or de novo anti-HLA antibodies. We
      discuss the appropriateness and clinical impact of IVIG and ECI in sensitized
      lung transplant recipients as well as cellular mechanisms that may contribute.

PMID- 15866702
TI  - Intravenous immunoglobulin for autoimmune thrombocytopenic purpura.
AB  - Severe autoimmune thrombocytopenic purpura is now commonly treated with high
      doses of intravenous immunoglobulins (IVIGs). Twenty-four years after this
      treatment was first demonstrated to be effective, several questions remain to be
      resolved. We review here current knowledge concerning the frequency and type of
      side effects and the likely mechanism of action of IVIGs. We suggest that the
      currently recommended dose of IVIG (2 g/kg) could be halved, that the total dose
      of IVIG should be administered as a single infusion, that nonresponders could be
      provided another equal dose on day 3, and that IVIG plus prednisolone should be
      considered the gold standard for treatment of the most severe forms of the
      disease. Treatment with anti-D immunoglobulin could be proposed as an alternative
      if the results recently obtained with high doses (75 microg/kg) are confirmed.
      Finally, because IVIG has only a transient effect, it cannot be considered a
      curative treatment for patients with chronic autoimmune thrombocytopenic purpura.

PMID- 15866703
TI  - High-dose intravenous immunoglobulins: an option in the treatment of systemic
      lupus erythematosus.
AB  - Despite encouraging reports on the efficacy of intravenous immunoglobulin (IVIG)
      therapy in systemic lupus erythematosus (SLE), the clinical value of this
      treatment is not well established, and most of the data are based on case reports
      and small series of patients. IVIG has been used successfully to treat SLE
      patients with a broad spectrum of clinical manifestations, such as refractory
      thrombocytopenia, pancytopenia, central nervous system (CNS) involvement,
      secondary antiphospholipid syndrome, and lupus nephritis. The beneficial effects
      of IVIG on overall disease activity are usually prompt, with marked improvement
      within a few days, but they are often of limited duration. Improvement lasts for
      several weeks after the last infusion, although clinical response could be
      maintained by continuous monthly IVIG infusions. IVIG therapy immunomodulates
      autoimmune diseases by interacting with various Fcgamma receptors in such a way
      that it downregulates activating FcRIIA and FcRIIC and/or upregulates inhibitory
      FcRIIB. However, in SLE, additional mechanisms include inhibition of complement
      mediated damage, modulation of production of cytokines and cytokine antagonists,
      modulation of T- and B-lymphocyte function, induction of apoptosis in lymphocytes
      and monocytes, downregulation of autoantibody production, manipulation of the
      idiotypic network, and neutralization of pathogenic autoantibodies. At present,
      IVIG in SLE is indicated either in severe cases that are nonresponsive to other
      therapeutic modalities, or when SLE can be controlled only with high-dose
      steroids; in such patients, IVIG thus becomes a useful steroid-sparing agent.
      However, this needs to be confirmed in double-blind, placebo-controlled studies.

PMID- 15866704
TI  - Mechanisms of intravenous immunoglobulin action in immune thrombocytopenic
      purpura.
AB  - The use of high-dose intravenous gamma immunoglobulin (IVIG) for the treatment of
      immune thrombocytopenic purpura (ITP) was first reported more than two decades
      ago. After the therapeutic benefit of IVIG was established in ITP, it was then
      successfully used to treat many other autoimmune diseases. Although a complete
      definition of the mechanism of IVIG action is still lacking, extensive research
      suggests that IVIG may achieve its therapeutic effects through multiple
      mechanisms. IVIG exerts immunomodulatory effects that may include antiidiotypic
      neutralization of antiplatelet antibodies, stimulation of Fcgamma receptor IIB
      expression, and inhibition of Fcgamma receptor-mediated platelet destruction.
      Recent work suggests that a large fraction of the benefit provided by IVIG may be
      the result of competitive inhibition of neonatal Fc receptor (FcRn) and IVIG
      induced acceleration of antiplatelet antibody elimination. This review provides
      an overview and critical discussion of mechanisms that may be responsible of IVIG
      effects in ITP.

PMID- 15866705
TI  - Neutralization of muscarinic receptor autoantibodies by intravenous
      immunoglobulin in Sjogren syndrome.
AB  - Autoantibodies that inhibit M3 muscarinic receptor (M3R)-mediated
      neurotransmission and cause bladder and bowel dysfunction have been reported in
      patients with Sjogren syndrome and belong to a family of functional
      autoantibodies that includes the thyroid-stimulating hormone receptor antibody
      present in Graves disease. We have recently reported that antiidiotypic
      antibodies present in pooled immunoglobulin (Ig) G or IgG from healthy
      individuals neutralize anti-M3R antibody-mediated inhibition of smooth muscle
      contraction in vitro. Here we extend these studies to the clinic by examining
      whether therapeutic doses of intravenous immunoglobulin (IVIG) provided to
      patients with autoimmune diseases neutralize anti-M3R activity in vivo and
      improve bladder and bowel symptoms. Three patients with primary Sjogren syndrome,
      dermatomyositis, and celiac disease, respectively, all of whom had anti-M3R
      activity on a functional bladder contractile assay, were provided a single course
      of IVIG at a dose of 400 mg/kg per day for 5 days. Anti-M3R activity was
      neutralized at 4 weeks after IVIG infusion, whereas levels of specific
      autoantibodies (anti-La, anti-Jo-1, and anti-tissue transglutaminase) were
      unchanged. Bladder and bowel scores revealed variable improvement after IVIG.
      Neutralization of anti-M3R activity by IVIG in vivo, presumably as a result of
      antiidiotypic antibodies directed specifically against anti-M3R autoantibodies,
      provides a clinical correlate of our in vitro findings. This offers a rationale
      for IVIG as a treatment for parasympathetic dysfunction in patients with
      autoantibodies inhibiting postganglionic cholinergic neurotransmission. We
      suggest the presence of a network of naturally occurring antiidiotypic antibodies
      that regulate the expression of functional autoantibodies against neuronal
      receptors and ion channels.

PMID- 15866706
TI  - Intravenous immunoglobulin treatment in autoimmune neurological disorders-
      effects on quality of life.
AB  - Autoimmune neurological disorders are very common. Health-related quality-of-life
      measures, obtained through a patient-oriented tool (a self-administered
      questionnaire), are now considered essential in the evaluation of therapies,
      especially for pathologies that may affect patients' general status. We reviewed
      the most common autoimmune neurological disorders and their treatment, and we
      report on our experience on intravenous immunoglobulin (IVIG) administration and
      the relationship between IVIG and health-related quality of life. Generally, IVIG
      administration is effective in the most common autoimmune neurological diseases.
      Concerning the relationship between IVIG treatment and health-related quality of
      life, our results reveal an improvement of physical aspects of patients' health
      related quality of life after IVIG administration. Conversely, the comparison of
      mental scores between the evaluation at baseline and the evaluation at follow-up
      exhibited no difference. Although the use of IVIG is effective for autoimmune
      neurological disorders, there are no commonly accepted protocols for the use of
      IVIG treatment. Further controlled studies on IVIG, including quality-of-life
      assessments, are necessary to develop needed evidence on the use of IVIG in
      clinical practice.

PMID- 15866707
TI  - Use of intravenous immunoglobulin in patients with acquired von Willebrand
      syndrome.
AB  - Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with
      laboratory findings similar to those for congenital von Willebrand disease.
      Unlike the congenital form, AVWS usually occurs in individuals with no personal
      or family history of bleeding disorders. According to an international registry,
      AVWS is mainly associated with lymphomyeloproliferative, immunologic, and
      cardiovascular disorders, as well as with solid tumors and other miscellaneous
      conditions; however, the prevalence of AVWS in these underlying disorders is
      still unknown. von Willebrand factor (VWF) is synthesized normally in most AVWS
      patients, and the low plasma VWF levels are from its accelerated removal from
      plasma by five different mechanisms, including autoantibodies. Because of the
      reduced half-life of endogenous-exogenous plasma VWF, bleeding of AVWS cannot be
      managed with desmopressin or factor VIII/VWF concentrates. Clinical use of
      intravenous immunoglobulin (IVIg) in AVWS has been reported since 1988. IVIg is
      most effective in AVWS with type immunoglobulin (Ig) G monoclonal gammopathies of
      undetermined significance and in other cases with IgG autoantibodies. IVIg can
      correct factor VIII and von Willebrand factor complex activities for about 15-20
      days, and repeated injections induce remission of AVWS in these patients.
      Prospective studies are required to evaluate the efficacy and safety of IVIg in
      AVWS.

PMID- 15866708
TI  - Molecular cloning, expression, and purification of SARS-CoV nsp13.
AB  - The SARS-nsp13 protein was identified as an mRNA cap1 methyltransferase. In this
      study, the nsp13 gene was cloned from the SARS-CoV PUMC02 strain viral RNA by RT
      PCR, and inserted into the expression plasmid pET30a(+). The recombinant plasmid
      pET30a(+)-nsp13 was confirmed by restriction enzymes and sequencing analysis, and
      transformed into Escherichia coli BL21(DE3). The His-tag-fused protein was
      expressed by induction of 0.5mM IPTG and purified by a single Ni(2+) affinity
      chromatography. The protein was validated by western blot and MS analysis. A
      large quantity of the nsp13 protein obtained with this method may be useful for
      further study of its structure and function.

PMID- 15866709
TI  - Isoforms of dipeptidyl aminopeptidase IV from Pseudomonas sp. WO24: role of the
      signal sequence and overexpression in Escherichia coli.
AB  - The complete nucleotide sequence of dipeptidyl aminopeptidase IV (DAP IV) from
      Pseudomonas sp. WO24 was determined. Nucleotide sequence analysis revealed an
      open reading frame of 2238bp, which was assigned to dap4 by N-terminal and
      internal amino acid sequences previously reported. The predicted amino acid
      sequence of DAP IV contains a serine protease Gly-X-Ser-X-Gly-Gly consensus motif
      and displays extensive homology to DAP IVs and the homologous proteins from
      eukaryotes and bacteria, belonging to the prolyl oligopeptidase family S9. In
      Pseudomonas sp. WO24, DAP IV is expressed as 82 and 84-kDa isoforms, having two
      Met, Met-1 and Met-12, in its N-terminal sequence. Met-1 of DAP IV was mutated to
      Gly and Met-12 was mutated to Ile, and we overexpressed the two mutated genes in
      Escherichia coli and obtained the recombinant 82 and 84-kDa proteins from the
      periplasm and the cytoplasm, respectively, suggesting that the 82 and 84-kDa
      isoforms are derived from the same gene and localize to different compartments in
      the cell. We developed purification steps for activting a large amount of 84-kDa
      isoform protein that will be useful for producing protein for crystallographic
      studies.

PMID- 15866710
TI  - Expression of soluble, biologically active recombinant human endostatin in
      Escherichia coli.
AB  - Endostatin, a 20kDa C-terminal fragment of collagen XVIII, is a potent anti
      angiogenic protein and inhibitor of tumor growth. Recombinant endostatin was
      prepared from Escherichia coli deposited as insoluble, inactive inclusion bodies.
      In the present study, we produced soluble and biologically active recombinant
      human endostatin (rhEndostatin) in E. coli by employing both co-expression of the
      molecular chaperones and lower temperature fermentation. Two groups of chaperones
      Trigger factor and GroEL-GroES (GroEL/ES), DnaK-DnaJ-GrpE and GroEL/ES, were co
      expressed, respectively, with rhEndostatin at different temperatures (37, 25, and
      16 degrees C). It revealed that low temperature or molecular chaperones alone
      could enhance the production of active rhEndostatin; meanwhile, combinational
      employment of low temperature cultivation (16 degrees C) together with co
      expression of DnaK-DnaJ-GrpE and GroEL/ES was more effective to prevent
      aggregation of rhEndostatin. The production of soluble rhEndostatin was about 36
      mg/L, and at least 16 mg of rhEndostatin was purified from 1L flask culture. The
      purified rhEndostatin specifically inhibited the proliferation of endothelial
      cell-bovine capillary endothelial cell in a dose-dependent manner, and it showed
      potent anti-angiogenic capability on the chorioallantoic membrane of chick embryo
      in vivo. Our study provides a feasible and convenient approach to produce soluble
      and biologically active rhEndostatin.

PMID- 15866711
TI  - Expression and purification of exendin-4, a GLP-1 receptor agonist, in
      Escherichia coli.
AB  - Exendin-4 is a 39 amino acid peptide isolated from salivary secretions of Gila
      monster (Heloderma suspectum). It shows 53% sequence similarity to glucagon-like
      peptide-1 (GLP-1), which is evaluated for the regulation of plasma glucose in
      type 2 diabetes. Exendin-4 is a potent and long-acting agonist of GLP-1 receptor.
      In the present study, the exendin-4 gene obtained by PCR with an enterokinase
      site at N-terminus and a termination codon at C-terminus was expressed in
      Escherichia coli strain BL21 (DE3) harboring pET32a(+). The fusion protein was
      purified by chromatography on Ni-NTA-agarose column. Recombinant exendin-4 was
      obtained by enterokinase cleavage of the fusion protein and subsequent
      purification. The yield of recombinant exendin-4 was 3.15mg/10g bacteria. The
      obtained recombinant exendin-4 shows glucose-lowering action in vivo.

PMID- 15866712
TI  - Construction and characterization of Pichia pastoris strains for labeling
      aromatic amino acids in recombinant proteins.
AB  - Strains of the methylotrophic yeast Pichia pastoris auxotrophic for the aromatic
      amino acids (tyrosine, phenylalanine, and tryptophan) have been constructed by
      targeted gene disruption for protein labeling applications. Three strains, with
      defects in ARO1 (coding for a homolog of the arom pentafunctional enzyme), ARO7
      (coding for chorismate mutase), and TYR1 (coding for prephenate dehydrogenase),
      have been engineered in a P. pastoris ura3Delta1 parent strain using standard
      methods. The nutritional requirements of these auxotrophic strains have been
      characterized and their utility as expression hosts for labeling recombinant
      proteins has been demonstrated. All three strains show a surprising sensitivity
      to rich culture medium and must be grown in supplemented minimal medium. The
      tyr1::URA3 strain in particular is strongly inhibited by tryptophan, and to a
      lesser extent by phenylalanine, leucine, and isoleucine. Highly efficient
      incorporation of exogenously supplied amino acids by these three auxotroph
      strains has been demonstrated using recombinant galactose oxidase.
      Stereochemically pure l-amino acids and racemic d,l-mixtures serve nearly equally
      well to support protein expression and labeling. These strains allow efficient
      labeling of aromatic amino acids in recombinant proteins, supporting NMR
      structural biology and a wide range of other biophysical studies.

PMID- 15866713
TI  - Generation of a vector system facilitating cloning of DMBT1 variants and
      recombinant expression of functional full-length DMBT1.
AB  - Deleted in malignant brain tumours 1 (DMBT1) codes for a approximately 340kDa
      glycoprotein with highly repetitive scavenger receptor cysteine-rich (SRCR)
      domains. DMBT1 was implicated in cancer, defence against viral and bacterial
      infections, and differentiation of epithelial cells. Recombinant expression and
      purification of DMBT1 is an essential step for systematic standardized functional
      research and towards the evaluation of its therapeutical potential. So far, DMBT1
      is obtained from natural sources such as bronchioalveolar lavage or saliva,
      resulting in time consuming sample collection, low yields, and protein
      preparations which may substantially vary due to differential processing and
      genetic polymorphism, all of which impedes functional research on DMBT1. Cloning
      of DMBT1 cDNAs is hampered because of the size and the 13 highly homologous SRCR
      exons. In this study, we report on the setup of a vector system that facilitates
      cloning of DMBT1 variants. We demonstrate applicability of the vector system by
      expression of the largest DMBT1 variant in a tetracycline-inducible mammalian
      expression system using the Chinese hamster ovary cell line. Yields up to 30 mg
      rDMBT1 per litre of cell culture supernatant could be achieved with an optimized
      production procedure. By harnessing the specific bacteria-binding property of
      DMBT1 we established an affinity purification procedure which allows the
      isolation of more than 3 mg rDMBT1 with a purity of about 95%. Although the
      glycosylation moieties of rDMBT1 are different from DMBT1(SAG) isolated from
      saliva, we demonstrate that rDMBT1 is functionally active in aggregating Gram
      positive and Gram-negative bacteria and binding to C1q and lactoferrin, which
      represent two known endogenous DMBT1 ligands.

PMID- 15866714
TI  - Recombinant expression of maize nucleotide excision repair protein Rad23 in
      Escherichia coli.
AB  - Nucleotide excision is a highly conserved DNA repair pathway for correcting DNA
      lesions that cause distortion of the double helical structure. The protein
      heterodimer XPC-Rad23 is involved in recognition of and binding to such lesions.
      We have isolated full-length cDNAs encoding two different members of the maize
      Rad23 family. The deduced amino acid sequences of both maize orthologues show a
      high degree of homology to plant and animal Rad23 proteins. The cDNA encoding
      maize Rad23A was cloned as an in-frame C-terminal fusion of glutathione S
      transferase. This chimera was expressed in Escherichia coli as a soluble protein
      and purified to homogeneity using glutathione-agarose followed by MonoQ column
      chromatography. Purified recombinant maize Rad23 protein was used to generate
      polyclonal antibodies that cross-react with a approximately 48-kDa protein in
      extracts from plant as well as mammalian cells. The purified recombinant protein
      and antibodies would be useful reagents to study the biochemistry of nucleotide
      excision repair in plants.

PMID- 15866715
TI  - Refolding of the full-length non-structural protein 3 of hepatitis C virus.
AB  - An easy and reproducible procedure for purification and refolding of the full
      length non-structural protein 3 (NS3) from hepatitis C virus has been developed.
      Refolding was achieved by simply diluting the protein into a suitable buffer. Low
      protein concentration, high pH, highly reducing conditions, the presence of
      detergent, and low viscosity were important parameters for high refolding
      efficiency. Refolding was insignificantly affected by the presence of Zn(2+) in
      the refolding buffer, while the addition of NS4A cofactor inhibited refolding. A
      comparison of the kinetic parameters showed that the refolded enzyme is not as
      catalytically competent as the native enzyme. Nevertheless, the activity of the
      refolded NS3 protease was dependent on the specific NS4A-peptide cofactor and was
      inhibited by the specific substrate-based NS3 protease inhibitor, which indicates
      that the refolded NS3 can be appropriate for inhibitor screening. The yield of
      pure protein from the insoluble fraction of cell lysate was 6 mg/L of bacterial
      culture, which is 18 times higher than obtained from the soluble fraction.
      Improvement of the refolding conditions has resulted in a 50-fold higher activity
      of the protease as compared to refolding in buffer with neutral pH and no
      additives.

PMID- 15866716
TI  - The C subunit of Ideonella dechloratans chlorate reductase: expression,
      purification, refolding, and heme reconstitution.
AB  - The C subunit of Ideonella dechloratans chlorate reductase has been expressed in
      Escherichia coli as a GST fusion protein. Purification from inclusion bodies,
      followed by refolding and reconstitution with heme, produced a protein with a
      heme/protein ratio of 0.4, and with UV-vis spectral characteristics similar to
      those of native chlorate reductase. Wavelength maxima for the alpha and beta
      bands in the reduced state were 559 and 529 nm for both native chlorate reductase
      and the reconstituted recombinant subunit, whereas the reduced Soret bands were
      found at 426 and 424 nm, respectively. These results support the notion of the C
      subunit as the cytochrome b moiety of I. dechloratans chlorate reductase.
      Moreover, the availability of a recombinant version of the C subunit is expected
      to facilitate further studies of electron transfer and protein interaction
      included in the reaction catalyzed by chlorate reductase.

PMID- 15866717
TI  - Overexpression and purification of recombinant human interferon alpha2b in
      Escherichia coli.
AB  - Overexpression of rhIFN-alpha2b was obtained by synthesizing a codon optimized
      gene for IFN-alpha2b and expressing it in the form of inclusion bodies (IBs) in
      Escherichia coli. The recombinant plasmid pRSET-IFNalpha, which had the IFN
      alpha2b gene under the T7 promoter, was coexpressed with plasmid pGP1-2, which
      carried the gene for T7 RNA polymerase under the heat inducible lambdaP(L)
      promoter. This two plasmid expression system was optimized with respect to heat
      shock time, media, and time of induction in shake flask cultures. This was then
      scaled up into a bioreactor to get a maximum volumetric product yield of 5.2g/L
      at a final OD(600) of 67. At this point, the IBs represented approximately 40% of
      the total cellular protein. This high specific product yields eased the further
      downstream processing steps and improved product recoveries. The IBs were
      isolated and purified through ion exchange followed by step refolding to give a
      final product yield of approximately 3g/L, which is maximum reported in the
      literature. The bioassay of the refolded protein gave a specific activity of
      approximately 3 x 10(9)IU/mg protein.

PMID- 15866718
TI  - Purification and characterization of recombinant human antithrombin containing
      the prelatent form in Chinese hamster ovary cells.
AB  - Antithrombin (AT) is a serine proteinase inhibitor and a major regulator of the
      blood coagulation cascade. AT in human plasma has two isoforms, a predominant
      alpha-isoform and a minor beta-isoform; the latter lacks N-glycosylation at Asn
      135 and has a higher heparin affinity. From the difference in its folding states,
      the AT molecule can be separated into three forms: a native form, a denatured and
      inactive form known as the latent form, and a partially denatured form called the
      prelatent form. In this study, we purified and characterized recombinant human AT
      (rAT) containing the prelatent form produced by Chinese hamster ovary (CHO)
      cells. When rAT was purified at physiological pH, its specific activity was lower
      than that of plasma-derived human AT (pAT). The latent and prelatent forms were
      detected in rAT by using hydrophobic interaction chromatography analysis.
      However, when rAT was purified at alkaline pH, the prelatent form was reversibly
      folded to the native form and the inhibitory activity of rAT increased to a value
      similar to that of pAT. Highly purified rAT was analyzed and compared with pAT by
      using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, circular
      dichroism spectroscopy, amino acid composition, N-terminal sequence,
      monosaccharide composition, peptide mapping, and heparin-binding affinity. From
      these analyses, rAT was found to be structurally identical to pAT, except for
      carbohydrate side-chains. rAT in CHO cells had a high beta-isoform content and it
      caused a higher heparin affinity than by pAT and also pH-dependent reversible
      inhibitory activity.

PMID- 15866719
TI  - Preparation of recombinant thioredoxin fused N-terminal proCNP: Analysis of
      enterokinase cleavage products reveals new enterokinase cleavage sites.
AB  - C-type natriuretic peptide (CNP) acts as a paracrine hormone to dilate blood
      vessels and is also required for the growth of long bones. In vivo, CNP is
      produced by cleavage from the C-terminal end of a larger proCNP peptide. The
      remaining N-terminal proCNP fragment (NT-proCNP) escapes into the circulation
      where its concentration is much higher than that of CNP due presumably to a lower
      clearance rate. Our strategy to obtain large quantities of pure NT-proCNP for
      further physiological investigations was to express it as a fusion protein with
      His(6)-tagged thioredoxin followed by cleavage using enterokinase to yield NT
      proCNP alone. We have successfully designed and artificially synthesized the
      coding sequence specifying both mouse and human NT-proCNP with built-in codon
      bias towards Escherichia coli codon preference. An enterokinase recognition
      sequence was incorporated immediately upstream of the NT-proCNP coding sequence
      to allow the fusion protein to be cleaved without leaving any extra residues on
      the NT-proCNP peptide. High levels of fusion proteins were obtained, constituting
      50-58% of total bacterial proteins. Greater than 90% of recombinant
      thioredoxin/NT-proCNP was expressed in the soluble form and purified to near
      homogeneity in a single chromatographic step using nickel as the metal ion in
      IMAC. A time course analysis of the products released from enterokinase cleavage
      of the recombinant proteins by ESI-MS revealed three sensitive secondary cleavage
      sites: two were located on vector-associated sequences linking the thioredoxin
      moiety and NT-proCNP, and one at the C-terminal end of NT-proCNP. Clearly,
      substrate specificity of both the native and recombinant forms of enterokinase
      for the recognition sequence DDDDK was by no means exclusive. Hydrolysis at the
      unexpected LKGDR site located towards the carboxyl end on NT-proCNP was
      significantly more efficient than at the internally sited DDDDK target sequence.
      However, when this same sequence was sited internally replacing the DDDDK in
      another construct of thioredoxin/mouse NT-proCNP, it was found to be poorly
      processed by enterokinase. Our results showed that non-target sequences can be
      preferentially recognized over the canonical DDDDK sequence when located
      accessibly at the ends of proteins.

PMID- 15866720
TI  - Gene cloning, bacterial expression, in vitro refolding, and characterization of a
      single-chain Fv antibody against PreS1(21-47) fragment of HBsAg.
AB  - The murine monoclonal antibody 125E11 is an IgG which recognizes PreS1(21-47)
      fragment of large hepatitis B surface antigen. It has been successfully used for
      clinical detection of HBV virion in serum of hepatitis B patients. In present
      study, the genes of variable region in heavy chain (VH) and light chain (VL) of
      125E11 have been cloned. Sequence analysis of cloned VH gene and VL gene showed
      that they had general characterization of immunoglobin variable region genes.
      According to Kabat classification, VH gene and VL gene belong to VH10 family,
      subgroup IIID and Vkappa family subgroup I, respectively. An expression vector of
      125E11 single-chain Fv antibody fusion protein, in which VH and VL peptide were
      connected by a flexible linker (Gly(4)Ser)(3), was constructed. The scFv fusion
      protein was highly expressed in Escherichia coli mainly in inclusion body form.
      Using urea and pH gradient gel filtration method, the refolding of scFv was
      efficiently achieved. The refolding efficiency reached about 11% and 2.7 mg
      refolded scFv was obtained from 1L of culture. The binding activity and
      specificity of 125E11 scFv against PreS1(21-47)-containing antigen were also
      analyzed.

PMID- 15866721
TI  - Purification and characterization of an extracellular alpha-amylase from Bacillus
      subtilis AX20.
AB  - A Bacillus subtilis AX20 from soil with ability to produce extracellular alpha
      amylases was isolated. The characterization of microorganism was performed by
      biochemical tests as well as 16S rDNA sequencing. Maximum amylase activity (38
      U/ml) was obtained at stationery phase when the culture was grown at 37 degrees
      C. The enzyme was purified to homogeneity with an overall recovery of 24.2% and
      specific activity of 4133 U/mg. The native protein showed a molecular mass of 149
      kDa composed of a homodimer of 78 kDa polypeptide by SDS-PAGE. The optimum pH and
      temperature of the amylase were 6 and 55 degrees C, respectively. The enzyme was
      inhibited by Hg(2+), Ag(2+), and Cu(2+) and it did not show an obligate
      requirement of metal ions. The enzyme was not inhibited by EDTA or EGTA,
      suggesting that this enzyme is not a metalloenzyme. The end products of corn
      starch and soluble starch were glucose (70-75%) and maltose (20-25%). Rapid
      reduction of blue value and the end products suggest an endo mode of action for
      the amylase. The purified amylase shows interesting properties useful for
      industrial applications.

PMID- 15866722
TI  - Purification, properties, and crystallization of Saccharomyces cerevisiae
      dihydropterin pyrophosphokinase-dihydropteroate synthase.
AB  - The tri-functional enzyme of Saccharomyces cerevisiae dihydroneopterin aldolase
      (DHNA)-dihydropterin pyrophosphokinase (PPPK)-dihydropteroate synthase (DHPS)
      catalyzes three sequential steps in folate biosynthesis. A cDNA encoding the PPPK
      and DHPS domains of the tri-functional enzyme has been cloned. This bi-functional
      enzyme was expressed as a His(6) fusion protein in Escherichia coli and the
      protein was purified to apparent homogeneity. The purified protein possesses both
      PPPK and DHPS activities as measured by the incorporation of [(3)H]p-ABA into the
      appropriate substrate. The pH optimum of the DHPS activity was determined to be
      8.5. Gel filtration measurement indicates that the protein exists as a dimer in
      solution. A robotic screening method was used to identify crystallization
      conditions. Bi-pyramidal crystals of the enzyme formed with the protein in the
      presence of a pterin substrate analog in phosphate buffer (pH 6.3) and these
      diffracted to 2.3A. Structural information from these crystals could be used to
      design novel drugs to inhibit folate biosynthesis.

PMID- 15866723
TI  - Open reading frame yjbI of Bacillus subtilis codes for truncated hemoglobin.
AB  - A hypothetical open reading frame from Bacillus subtilis genome, yjbI [NCBI
      genome database Accession No. ] having homology to many globin and globin-like
      proteins from different microbial genomes, was selectively amplified from the
      chromosomal DNA of B. subtilis strain DB104 based on genome sequence database of
      B. subtilis strain 168. The gene was cloned and over-expressed in Escherichia
      coli under the transcriptional control of tandem lambda P(L) and P(R) promoters,
      and the protein was purified to homogeneity. The single-chain monomeric
      hemoglobin-like protein is stable to the extent of 5.45 kcal/mol at 25 degrees C,
      binds carbon mono-oxide, and shows optical spectra characteristic of
      hemoproteins. The protein also exhibits peroxidase-like activity. This is the
      first report of a truncated bacterial globin endowed with peroxidase-like
      activity. The activity is enhanced in the presence of urea and guanidine
      hydrochloride, more so in the presence of the latter. Presumably, only a small
      portion of the protein is involved in peroxidase activity, which is exposed with
      increasing concentration of the denaturants.

PMID- 15866724
TI  - Characterization of different cell culture media for expression of recombinant
      antibodies in mammalian cells: Presence of contaminating bovine antibodies.
AB  - Several new cell culture media designed specifically for the expression of
      recombinant antibodies in Chinese hamster ovary (CHO) cells were investigated for
      the presence of bovine IgG. Three serum-free media, three protein-free (animal
      component free) media, as well as one chemically defined medium were included in
      the study. Employing a combination of affinity chromatography (Protein G or A
      columns), SDS-PAGE analysis, and peptide mass fingerprinting, two of the serum
      free media were found to contain bovine IgG in the range of approximately 0.5
      mg/L. The other five media did not contain detectable levels of contaminating
      Protein A or G-binding proteins such as bovine IgG.

PMID- 15866725
TI  - Cloning and sequence analysis of the Korean strain of spike gene of porcine
      epidemic diarrhea virus and expression of its neutralizing epitope in plants.
AB  - Porcine epidemic diarrhea virus (PEDV) causes acute diarrhea and dehydration in
      pigs and leads to death with a high mortality rate, which has been reported
      notably in Korea. The spike (S) gene of the PEDV isolated in Korea was cloned and
      sequenced. The nucleotide sequence encoding the entire S gene open reading frame
      of Korean strain was 4161 bases long encoding 1387 amino acids. The neutralizing
      epitope of Korean PEDV (K-COE) was expressed in tobacco plants using
      Agrobacterium-mediated protein transformation. The recombinant K-COE constituted
      up to 0.1% of the total soluble protein in the leaves of transgenic tobacco
      plants. The result of this study opens the way for the development of an edible
      vaccine against PEDV infection in Korea.

PMID- 15866726
TI  - Characterisation of tyrosine-phosphorylation-defective calmodulin mutants.
AB  - Using site-directed mutagenesis, we have produced three calmodulin (CaM) mutants
      in which one or the two tyrosine residues of native CaM were substituted by
      phenylalanine. The three variants, denoted CaM(Y99F), CaM(Y138F), and
      CaM(Y99F/Y138F), were highly expressed in transformed Escherichia coli
      BL21(DE3)pLysS and purified in high yield. The three CaM mutants were able to
      activate the cyclic nucleotide phosphodiesterase and the plasma membrane Ca(2+)
      ATPase, and present the characteristic Ca(2+)-induced electrophoretic mobility
      shift of native CaM. CaM(Y138F) and CaM(Y99F/Y138F), however, showed a slightly
      higher electrophoretic mobility than CaM(Y99F) or wild type CaM. The molar
      extinction coefficient of native CaM at 276 nm decreases 50% in CaM(Y99F) and
      CaM(Y138F), while the 276nm peak disappears in CaM(Y99F/Y138F). Terbium
      fluorescence studies with the different CaM mutants indicate that Y99 (but not
      Y138) closely interacts with Ca(2+) in the III Ca(2+)-binding domain. The
      epidermal growth factor receptor (EGFR) and the non-receptor tyrosine kinase c
      Src phosphorylate CaM(Y99F) and CaM(Y138F) at a lesser extent than wild type CaM,
      while they fail to phosphorylate CaM(Y99F/Y138F) as expected. All resulting
      phospho-(Y)CaM species present the characteristic Ca(2+)-induced electrophoretic
      mobility shift observed in non-phosphorylated CaM. Quantitative analysis of the
      different phospho-(Y)CaM species suggests that the relative phosphorylation of
      Y99 and Y138 in wild type CaM by both the EGFR and c-Src is different than the
      respective phosphorylation of either Y99 in CaM(Y138F) or Y138 in CaM(Y99F).

PMID- 15866727
TI  - Purification and characterization of the creatine transporter expressed at high
      levels in HEK293 cells.
AB  - The bovine creatine transporter (CreaT) has been purified from membranes of
      HEK293 cells stably expressing high levels of the transporter. Membranes were
      solubilized with decyl maltoside and the CreaT was purified (90% pure) by
      affinity chromatography on wheat germ agglutinin (WGA)-Sepharose and gel
      filtration. The CreaT was shown to be an approximately 70 kDa glycoprotein by SDS
      polyacrylamide gel electrophoresis and Western blotting. Identification of the
      CreaT was confirmed by sequencing tryptic peptides by mass spectrometry. Laser
      light scattering showed the majority of the CreaT to be present as a 224 kDa
      species. Additional purification was obtained when the Creat was eluted from the
      WGA column and purified by gel-filtration in Fos-choline 12 instead of decyl
      maltoside, followed by a second WGA affinity step to exchange the detergent for
      sodium cholate. This resulted in a 30-fold purification (95% purity) of the
      approximately 70kDa CreaT, with a yield of 15%. From this, it is estimated that
      the CreaT comprises approximately 3% of total HEK293-CreaT membrane protein. Gel
      filtration showed the transporter to migrate with an apparent molecular mass of
      210 kDa. Circular dichroism showed a predominantly alpha-helical structure,
      consistent with the 12 transmembrane domains predicted for the transporter. This
      work has enabled the purification of the CreaT in amounts ( approximately 100
      microg) that make it feasible to consider structural studies of a member of the
      Na(+)- and Cl(-)-dependent neurotransmitter transporter family.

PMID- 15866728
TI  - Expression of a novel recombinant stem cell factor/macrophage colony-stimulating
      factor fusion protein in baculovirus-infected insect cells.
AB  - A novel human stem cell factor (SCF)/macrophage colony-stimulating factor (M-CSF)
      fusion protein gene was constructed, in which the coding regions of human SCF
      cDNA (1-165aa) and the truncated M-CSF cDNA (1-149aa) were connected by a linker
      sequence encoding a short peptide GGGGSGGGGSGG. The SCF/M-CSF gene was cloned
      into baculovirus transfer vector pVL1392 under the control of polyhedrin promoter
      and expressed in the Sf9 cells (Spodoptera frugiperda). SDS-PAGE and Western blot
      analysis showed that the purified fusion protein was a homodimer with a molecular
      weight about 84kDa under non-reducing conditions or a monomer about 42kDa under
      reducing conditions. The specific activity of rhSCF/M-CSF was 17 times as high as
      that of monomeric rhSCF to stimulate the proliferation of TF-1 cell. The results
      of macrophages colony-forming (CFU-M) assay performed with human bone marrow
      mononuclear cells demonstrated that rhSCF/M-CSF was more potent in promoting CFU
      M than the equimolar of SCF, M-CSF or that of two cytokines mixture.

PMID- 15866729
TI  - Expression and preparation of recombinant hepcidin in Escherichia coli.
AB  - Hepcidin is a low-molecular-weight, highly disulfide bonded peptide relevant to
      small intestine iron absorption and body iron homeostasis. In this work, hepcidin
      was expressed in Escherichia coli as a 10.5 kDa fusion protein (His-hepcidin)
      with a N-terminal hexahistidine tag. The expressed His-hepcidin existed in the
      form of inclusion bodies and was purified by IMAC under denaturation condition.
      Since the fusion partner for hepcidin did not contain other cysteine residues,
      the formation of disulfide bonds was performed before the His-tag was removed.
      Then, the oxidized His-hepcidin monomer was separated from protein multimers
      through gel filtration. Following monomer refolding, hepcidin was cleaved from
      fusion protein by enterokinase and purified with reverse-phase chromatography.
      The recombinant hepcidin exhibited obvious antibacterial activity against
      Bacillus subtilis.

PMID- 15866730
TI  - Production of constitutively acetylated recombinant p53 from yeast and
      Escherichia coli by tethered catalysis.
AB  - Post-translational modification of proteins is a dynamic way of generating new
      protein-protein interaction interfaces that are critical for signaling networks
      in diverse cellular functions. Purified recombinant proteins frequently lack
      these signature modifications. Using the tumor suppressor p53 as the model
      protein, we present here a tethered catalysis approach for the production of
      acetylated p53 in vivo. P53 is a major tumor suppressor protein that protects the
      cell from various oncogenic stresses. Upon DNA damage, p53 is stabilized and
      activated by a plethora of post-translational modifications, including
      acetylation. Here, we show that constitutively acetylated p53 can be expressed
      and purified from both yeast and Escherichia coli. This method is highly suitable
      for studying protein-protein interactions in the conventional yeast two-hybrid
      screen that requires a constitutively acetylated state of p53. Furthermore,
      effective production and purification of acetylated p53 from E. coli supports
      future biochemical and structural characterization. The method described in this
      work can be applied to other proteins and modifications, and thus has widespread
      use in the fields of signal transduction and proteomic research.

PMID- 15866731
TI  - Coexpression of folding accessory proteins for production of active cyclodextrin
      glycosyltransferase of Bacillus macerans in recombinant Escherichia coli.
AB  - Coexpression of folding accessory proteins, molecular chaperones, and human
      peptidyl-prolyl cis-trans isomerase (PPIase) increased production of active
      cyclodextrin glycosyltransferase (CGTase) of Bacillus macerans, which is
      otherwise mainly expressed as inclusion body in recombinant Escherichia coli. The
      best partner for soluble expression of CGTase was found to be human PPIase
      followed by coexpression of DnaK-DnaJ-GrpE together with GroEL-GroES. Such a
      significant enhancement by human PPIase coexpression seemed to be due to dual
      functions of chaperone and peptidyl-prolyl cis-trans isomerization. Coexpression
      of GroEL-GroES or minichaperone alone did not influence the specific CGTase
      activity. For production of active CGTase in large amounts, a high cell density
      culture was achieved using a pH-stat fed-batch strategy. The optimized fed-batch
      fermentation resulted in dry cell weight of 103.4 g/L and CGTase activity of 1200
      U/mL. Combination of human PPIase expression at a gene level and cell culture
      optimization at a process scale exerted a synergistic effect on the product yield
      of soluble CGTase expression in recombinant E. coli.

PMID- 15866732
TI  - Increased expression of a bacterial phosphotriesterase in Escherichia coli
      through directed evolution.
AB  - We devised a growth-based strategy for screening phosphotriesterase mutant
      libraries for variants with enhanced activity towards organophosphates that
      generate dimethyl phosphate when hydrolysed. Phosphotriesterase mutants were
      screened for activity by growing transformed Escherichia coli on agar plates
      containing methyl paraoxon as a sole phosphorus source. E. coli is capable of
      growth under these conditions when coexpressing the phosphotriesterase from
      Agrobacterium radiobacter P230 (OpdA) and the glycerophosphodiester
      phosphodiesterase from Enterobacter aerogenes (GpdQ). The latter enzyme can
      hydrolyse the dimethyl phosphate produced by the phosphotriesterase to methyl
      phosphate, which can then be used by E. coli as a source of phosphate.
      Phosphotriesterase was expressed from the lac promoter at levels such that its
      activity was growth-rate limiting. Cultures of the largest colonies (1% of the
      transformants) were assayed for activity towards paraoxon spectrophotometrically
      in microtitre plates. This process produced E. coli variants with higher whole
      cell activity than wild-type, which was found to be a consequence of increased
      protein expression rather than any increase in enzymatic activity. The mutations
      present in these mutant enzymes with increased expression were exclusively in the
      coding region, suggesting the improvement occurs post-transcriptionally.

PMID- 15866733
TI  - Purification and characterization of human caseinomacropeptide produced by a
      recombinant Saccharomyces cerevisiae.
AB  - Caseinomacropeptide (CMP) is a biologically active polypeptide derived from the C
      terminal of milk kappa-casein. CMP is heterogeneous since it is modified
      differently by glycosylation and phosphorylation after translation. Recently,
      recombinant human CMP (hCMP) has been produced as a secretory product in yeast.
      The present study aimed at the purification and characterization of recombinant
      hCMP. By sequential molecular cut-off ultrafiltration and anion-exchange
      chromatography, the recombinant hCMP in the culture broth could be purified to an
      HPLC purity over 94%. The authenticity of the purified hCMP was confirmed by
      sequence analysis of N-terminal amino acids. The recombinant hCMP was estimated
      to be 7.0kDa by SDS-PAGE, and showed a lower glycosylation than the natural
      bovine CMP.

PMID- 15866734
TI  - Bacterial expression and characterization of rat apolipoprotein E.
AB  - Apolipoprotein (apo) E is a protein involved in both lipid metabolism and
      neuroprotection. Recently, it has been suggested that apoE may play a role in the
      regulation of food intake and body weight in rodents. However, rodent plasma apoE
      is difficult to purify in reasonable amounts due to numerous time-consuming
      steps. To circumvent this, we created a bacterial expression system for the
      efficient production of large amounts of rat apoE. We inserted rat apoE DNA into
      the pET30 expression vector and overexpressed the proteins in Escherichia coli
      strain BL21 (DE3). A histidine tag present at the N-terminus allowed for easy
      purification of the recombinant protein. The tag was removed with an IgA protease
      (Igase) from Neisseria gonorrhoeae leaving the mature form of the protein. The
      use of Igase was important as several more common proteases routinely cleave
      apolipoproteins at undesired sites. The recombinant protein was then compared
      both structurally and functionally to rat plasma apoE. This expression system
      will be highly useful for probing the ability of rat apoE to mediate food intake
      in rats.

PMID- 15866735
TI  - Expression and purification of Huwentoxin-I in baculovirus system.
AB  - Huwentoxin-I (HWTX-I) is a novel neurotoxin isolated from the venom of
      Orinithoctonus huwena. Based on its biological activity, HWTX-I could be
      developed as a pain-killer for clinical purpose. Production of HWTX-I by the
      bacterium or yeast expression systems resulted in poor yields and the purified
      protein was proved to have lower biological activity than that of native one. So,
      for the first time, we introduced a new method to express HWTX-I gene in Sf9
      cells using baculovirus expression system. Recombinant HWTX-I was recognized by
      Western blotting and then purified by nickel-chelating affinity chromatography
      under native conditions. Recombinant HWTX-I showed identical amino acid sequence
      as native form and exhibited similar effect on muscular transmission with that of
      native form. These results indicate that the baculovirus expression system and
      native purification strategy are viable ways to produce active HWTX-I.

PMID- 15866736
TI  - Model structures of alpha-2 adrenoceptors in complex with automatically docked
      antagonist ligands raise the possibility of interactions dissimilar from agonist
      ligands.
AB  - Antagonist binding to alpha-2 adrenoceptors (alpha2-ARs) is not well understood.
      Structural models were constructed for the three human alpha2-AR subtypes based
      on the bovine rhodopsin X-ray structure. Twelve antagonist ligands (including
      covalently binding phenoxybenzamine) were automatically docked to the models. A
      hallmark of agonist binding is the electrostatic interaction between a positive
      charge on the agonist and the negatively charged side chain of D3.32. For
      antagonist binding, ion-pair formation would require deviations of the models
      from the rhodopsin structural template, e.g., a rotation of TM3 to relocate D3.32
      more centrally within the binding cavity, and/or creation of new space near
      TM2/TM7 such that antagonists would be shifted away from TM5. Thus, except for
      the quinazolines, antagonist ligands automatically docked to the model structures
      did not form ion-pairs with D3.32. This binding mode represents a valid
      alternative, whereby the positive charge on the antagonists is stabilized by
      cation-pi interactions with aromatic residues (e.g., F6.51) and antagonists
      interact with D3.32 via carboxylate-aromatic interactions. This binding mode is
      in good agreement with maps derived from a molecular interaction library that
      predicts favorable atomic contacts; similar interaction environments are seen for
      unrelated proteins in complex with ligands sharing similarities with the alpha2
      AR antagonists.

PMID- 15866737
TI  - Electron tomography of degenerating neurons in mice with abnormal regulation of
      iron metabolism.
AB  - Previous studies have shown that IRP1(+/-) IRP2(-/-) knockout mice develop
      progressive neurodegenerative symptoms similar to those observed in human
      movement disorders such as Parkinson's disease. Histological investigations using
      optical microscopy show that these IRP knockout mice display accumulation of
      ferritin in axonal tracts in the brain, suggesting a possible role for excess
      ferritin in mediating axonal degeneration. Direct observation of the 3D
      distribution of ferritin by electron tomography indicates that ferritin amounts
      are increased by 3- to 4-fold in selected regions of the brain, and structural
      damage is observed within the axon as evidenced by the loss of the internal
      network of filaments, and the invaginations of neighboring oligodendrocyte
      membranes into the axonal medium. While optical microscopic investigations
      suggest that there is a large increase in ferritin in the presumptive axonal
      regions of the IRP knockout mice, electron tomographic studies reveal that most
      of the excess ferritin is localized to double-walled vesicular compartments which
      are present in the interior of the axon and appear to represent invaginations of
      the oligodendrocyte cells into the axon. The amount of ferritin observed in the
      axonal space of the knockout mice is at least 10-fold less than the amount of
      ferritin observed in wild-type mouse axons. The surprising conclusion from our
      analysis, therefore, is that despite the overall increase in ferritin levels in
      the knockout mouse brain, ferritin is absent from axons of degenerating neurons,
      suggesting that trafficking is compromised in early stages of this type of
      neuronal degeneration.

PMID- 15866738
TI  - The hydrophobic domain 26 of human tropoelastin is unstructured in solution.
AB  - Elastin is the protein responsible for the elastic properties of vertebrate
      tissue. Very little is currently known about the structure of elastin or of its
      soluble precursor tropoelastin. We have used high-resolution solution NMR methods
      to probe the conformational preferences of a conserved hydrophobic region in
      tropoelastin, domain 26 (D26). Using a combination of homonuclear, 15N-separated
      and triple resonance experiments, we have obtained essentially full chemical
      shift assignments for D26 at 278K. An analysis of secondary chemical shift
      changes, as well as NOE and 15N relaxation data, leads us to conclude that this
      domain is essentially unstructured in solution and does not interact with intact
      tropoelastin. D26 does not display exposed hydrophobic clusters, as expected for
      a fully unfolded protein and commensurate with an absence of flexible structural
      motifs, as identified by lack of binding of the fluorescent probe 4,4'-dianilino
      1,1'-binaphthyl-5,5'-disulfonic acid. Sedimentation equilibrium data establish
      that this domain is strictly monomeric in solution. NMR spectra recorded at 278
      and 308K indicate that no significant structural changes occur for this domain
      over the temperature range 278-308K, in contrast to the characteristic
      coacervation behavior that is observed for the full-length protein.

PMID- 15866739
TI  - Hemoglobin C modulates the surface topography of Plasmodium falciparum-infected
      erythrocytes.
AB  - There is a well-established clinical association between hemoglobin genotype and
      innate protection against Plasmodium falciparum malaria. In contrast to normal
      hemoglobin A, mutant hemoglobin C is associated with substantial reductions in
      the risk of severe malaria in both heterozygous AC and homozygous CC individuals.
      Irrespective of hemoglobin genotype, parasites may induce knob-like projections
      on the erythrocyte surface. The knobs play a major role in the pathogenesis of
      severe malaria by serving as points of adherence for P. falciparum-infected
      erythrocytes to microvascular endothelia. To evaluate the influence of hemoglobin
      genotype on knob formation, we used a combination of atomic force and light
      microscopy for concomitant topographic and wide-field fluorescence imaging.
      Parasitized AA, AC, and CC erythrocytes showed a population of knobs with a mean
      width of approximately 70 nm. Parasitized AC and CC erythrocytes showed a second
      population of large knobs with a mean width of approximately 120 nm. Furthermore,
      spatial knob distribution analyses demonstrated that knobs on AC and CC
      erythrocytes were more aggregated than on AA erythrocytes. These data support a
      model in which large knobs and their aggregates are promoted by hemoglobin C,
      reducing the adherence of parasitized erythrocytes in the microvasculature and
      ameliorating the severity of a malaria infection.

PMID- 15866740
TI  - Filaments of the Ure2p prion protein have a cross-beta core structure.
AB  - Formation of filaments by the Ure2 protein constitutes the molecular mechanism of
      the [URE3] prion in yeast. According to the "amyloid backbone" model, the N
      terminal asparagine-rich domains of Ure2p polymerize to form an amyloid core
      fibril that is surrounded by C-terminal domains in their native conformation.
      Protease resistance and Congo Red binding as well as beta-sheet content detected
      by spectroscopy-all markers for amyloid-have supported this model, as has the
      close resemblance between 40 A N-domain fibrils and the fibrillar core of intact
      Ure2p filaments visualized by cryo-electron microscopy and scanning transmission
      electron microscopy. Here, we present electron diffraction and X-ray diffraction
      data from filaments of Ure2p, of N-domains alone, of fragments thereof, and of an
      N-domain-containing fusion protein that demonstrate in each case the 4.7A
      reflection that is typical for cross-beta structure and highly indicative of
      amyloid. This reflection was observed for specimens prepared by air-drying with
      and without sucrose embedding. To confirm that the corresponding structure is not
      an artifact of air-drying, the reflection was also demonstrated for specimens
      preserved in vitreous ice. Local area electron diffraction and X-ray diffraction
      from partially aligned specimens showed that the 4.7A reflection is meridional
      and therefore the underlying structure is cross-beta.

PMID- 15866741
TI  - Spectroscopic studies on native and protofibrillar insulin.
AB  - The structure of insulin in amyloid fibrillar form has been recently shown as a
      well folded conformation using cryoelectron microscopy [Jimenez, J.L., Nettleton,
      E.J., Bouchard, M., Robinson, C.V., Dobson, C.M., Saibil H.R., 2002. The
      protofilament structure of insulin amyloid fibrils. Proc. Natl. Acad. Sci. USA.
      99 9196-9201.]. Most of the amyloid aggregates elicit maximum toxicity in the
      protofibrillar (PF) intermediate state. Here, we describe PF intermediates of
      insulin are made-up monomers with flexible conformers. We also show protofibrils
      have three-dimensionally extended hydrophobic cavity to bind with 1
      anilinonaphthalene-8-sulphonate (ANS) molecules. Energy transfer measurement
      revealed that ANS dye binding site of PF is within the range of FRET distance of
      insulin tyrosine residues. Significant proportion of beta-sheet, helical, and
      turn structures in the PF form indicate conformational dynamics in the folded
      chain of insulin in the PF assembled form. Though the conformational flexibility
      is noticeably present in the assembly, addition of GdnHCl could completely unfold
      PF into disordered structure suggesting structural "zipping" in the PF form. We
      have also shown that helical conformer inducing solvent 2,2,2-trifluoroethanol
      (TFE) could dissociate the PF aggregate indicating possible involvement of beta
      sheets in contributing to PF stability.

PMID- 15866742
TI  - Architecture of the organic matrix in the sternal CaCO3 deposits of Porcellio
      scaber (Crustacea, Isopoda).
AB  - Before the molt terrestrial isopods resorb calcium from the posterior cuticle and
      store it in large deposits within the first four anterior sternites. In Porcellio
      scaber the deposits consist of three structurally distinct layers consisting of
      amorphous CaCO3 (ACC) and an organic matrix that consists of concentric and
      radial elements. It is thought that the organic matrix plays a role in the
      structural organization of deposits and in the stabilization of ACC, which is
      unstable in vitro. In this paper, we present a thorough analysis of the
      ultrastructure of the organic matrix in the CaCO3 deposits using high-resolution
      field-emission scanning electron microscopy. The spherules and the homogeneous
      layer contain an elaborate organic matrix with similar structural organization
      consisting of concentric reticules and radial strands. The decalcification
      experiments reveal an inhomogeneous solubility of ACC within the spherules
      probably caused by variations in the stabilizing properties of matrix components.
      The transition between the three layers can be explained by changes in the number
      of spherule nucleation sites.

PMID- 15866743
TI  - Calcium-dependent human erythrocyte cytoskeleton stability analysis through
      atomic force microscopy.
AB  - Erythrocytes affected by age and diseases such as sickle cell anemia,
      hypertension, diabetes, etc., exhibit abnormally high intracellular Ca2+ ion
      levels, and appear to have altered cytoskeleton properties. It has been proposed
      that extra binding of Ca2+ to membrane-associated calmodulin attenuates the
      spectrin-ankyrin-Band 3 tether of the cytoskeleton to the cytoplasmic membrane
      and might change the cytoskeleton structure. Due to the close apposition of the
      network, direct observation of such a structural change in vivo is restricted. In
      this study, atomic force microscopy and quantitative image analysis were applied
      to investigate the structural change of young healthy erythrocyte cytoskeletons
      upon extra Ca2+ binding to the cytoplasmic membrane in vitro. The results show
      that extra Ca2+ binding increased the cytoskeleton rigidity and prevented
      spectrin aggregation during sample preparation. The cytoskeleton morphology
      observed in Ca2+ -incubated healthy young cell were similar to the glutaraldehyde
      fixed healthy young cells.

PMID- 15866744
TI  - Estimating alignment errors in sets of 2-D images.
AB  - We describe a robust and accurate method for the estimation of alignment errors
      for a set of two-dimensional images, in the case where the true pattern is
      unknown. The intended application of the proposed method is cryo-electron
      microscopy, where two-dimensional views of individual proteins in random
      orientations are observed in the electron microscope at low signal-to-noise
      ratio. By representing images in the basis of Fourier-harmonic coordinates and
      constructing averages and average intensities, we demonstrate that the variances
      of translation and rotational errors as well as of the Gaussian noise can be
      recovered. This machinery therefore allows one to isolate the various categories
      of errors that impede the quality of results in single particle reconstructions
      into constituent parts: translational errors, rotational errors, and additive
      noise.

PMID- 15866745
TI  - Restricted diffusion of DNA segments within the isolated Escherichia coli
      nucleoid.
AB  - To study the dynamics and organization of the DNA within isolated Escherichia
      coli nucleoids, we track the movement of a specific DNA region. Labeling of such
      a region is achieved using the Lac-O/Lac-I system. The Lac repressor-GFP fusion
      protein binds to the DNA section where tandem repeats of the Lac operator are
      inserted, which allows us to monitor the motion of the DNA. The movement of such
      a GFP spot is followed at 48 ms temporal resolution during 12s. The spots are
      found to diffuse within a confined space, so that the nucleoid appears to behave
      like a viscoelastic network. The distribution of the "particle" position in time
      can be fitted to a Gaussian function indicating that the motion of the particle
      is Brownian. An average self-diffusion constant Ds=0.12 microm(2) s-1 is derived
      via the time auto-correlation functions of the displacement and is compatible
      with the collective diffusion coefficient measured previously by dynamic light
      scattering. Restriction of a DNA sequence to a small region of the nucleoid is
      tentatively related to the existence of so-called supercoiling domains.

PMID- 15866747
TI  - Health, equity, and the built environment.

PMID- 15866748
TI  - Scientific vision: setting forth a strategy.

PMID- 15866749
TI  - Maternal and paternal risk factors for hypospadias.

PMID- 15866750
TI  - Exposure to environmental tobacco smoke and cognitive abilities among U.S.
      children and adolescents.

PMID- 15866752
TI  - Health on the banks of the Rio Grande.

PMID- 15866753
TI  - Dwelling disparities: how poor housing leads to poor health.
AB  - In recent years, environmental health science has broadened the scope of its
      inquiries, expanding its investigations beyond the effects of single pollutants
      on individuals to incorporate the entire panorama of external factors that may
      affect people's health. Consideration of the health impacts of the built
      environment-the human-modified places where we live, work, play, shop, and more
      has been a key element in the ongoing evolution of the field of environmental
      health.

PMID- 15866754
TI  - On closer inspection: learning to look at the whole home environment.

PMID- 15866756
TI  - Chromosomal aberrations in lymphocytes of healthy subjects and risk of cancer.
AB  - There is evidence that increased frequency of chromosomal aberration (CA) in
      peripheral blood lymphocytes is a predictor of cancer, but further data are
      needed to better characterize CA as marker of cancer risk. From the archives of
      15 laboratories we gathered cytogenetic records of 11,834 subjects who were free
      of cancer at the moment of blood drawing and who underwent cytogenetic
      examination for preventive purposes in the Czech Republic during 1975-2000. We
      linked these records to the national cancer registry, revealing a total of 485
      cancer cases. Subjects were classified according to the percentiles of CA
      distribution within each laboratory as low (0-33rd percentile), medium (34-66th
      percentile), and high (66-100th percentile). Subjects were further classified by
      occupational exposure and by subclass of CA. We found a significant association
      between the overall cancer incidence and the presence of chromosome-type
      aberrations [relative risk (RR) for high vs. low CA level = 1.24; 95% confidence
      interval (CI), 1.03-1.50] but not chromatid-type aberrations. Stomach cancer
      showed a strong association with frequency of total CA (RR = 7.79; 95% CI, 1.01
      60.0). The predictivity of CA observed in subjects exposed to various classes of
      carcinogens did not significantly differ from the group of nonexposed subjects.
      This study contributes to validation of CA as a predictive marker of cancer risk,
      in particular, of stomach cancer; the association between CA frequency and cancer
      risk might be limited to chromosome-type aberrations.

PMID- 15866757
TI  - Mercury, food webs, and marine mammals: implications of diet and climate change
      for human health.
AB  - We modeled the flow of methyl mercury, a toxic global pollutant, in the Faroe
      Islands marine ecosystem and compared average human methyl mercury exposure from
      consumption of pilot whale meat and fish (cod, Gadus morhua) with current
      tolerable weekly intake (TWI) levels. Under present conditions and climate change
      scenarios, methyl mercury increased in the ecosystem, translating into increased
      human exposure over time. However, we saw greater changes as a result of changing
      fishing mortalities. A large portion of the general human population exceed the
      TWI levels set by the World Health Organization [WHO; 1.6 microg/kg body weight
      (bw)], and they all exceed the reference dose (RfD) of 0.1 microg/kg bw/day set
      by the U.S. Environmental Protection Agency (EPA; equivalent to a TWI of 0.7
      microg/kg bw). As a result of an independent study documenting that Faroese
      children exposed prenatally to methyl mercury had reduced cognitive abilities,
      pregnant women have decreased their intake of whale meat and were below the TWI
      levels set by the WHO and the U.S. EPA. Cod had approximately 95% lower methyl
      mercury concentrations than did pilot whale. Thus, the high and harmful levels of
      methyl mercury in the diet of Faroe Islanders are driven by whale meat
      consumption, and the increasing impact of climate change is likely to exacerbate
      this situation. Significantly, base inflow rates of mercury into the environment
      would need to be reduced by approximately 50% to ensure levels of intake below
      the WHO TWI levels, given current levels of whale consumption.

PMID- 15866758
TI  - Developmental exposure of rats to chlorpyrifos leads to behavioral alterations in
      adulthood, involving serotonergic mechanisms and resembling animal models of
      depression.
AB  - Developmental exposure to chlorpyrifos (CPF) causes persistent changes in
      serotonergic (5HT) systems. We administered 1 mg/kg/day CPF to rats on postnatal
      days 1-4, a regimen below the threshold for systemic toxicity. When tested in
      adulthood, CPF-exposed animals showed abnormalities in behavioral tests that
      involve 5HT mechanisms. In the elevated plus maze, males treated with CPF spent
      more time in the open arms, an effect seen with 5HT deficiencies in animal models
      of depression. Similarly, in an anhedonia test, the CPF-exposed group showed a
      decreased preference for chocolate milk versus water. Developmental CPF exposure
      also has lasting effects on cognitive function. We replicated our earlier finding
      that developmental CPF exposure ablates the normal sex differences in 16-arm
      radial maze learning and memory: during acquisition training, control male rats
      typically perform more accurately than do control females, but CPF treatment
      eliminated this normal sex difference. Females exposed to CPF showed a reduction
      in working and reference memory errors down to the rate of control males.
      Conversely, CPF-exposed males exhibited an increase in working and reference
      memory errors. After radial-arm acquisition training, we assessed the role of 5HT
      by challenging the animals with the 5HT2 receptor antagonist ketanserin.
      Ketanserin did not affect performance in controls but elicited dose-dependent
      increases in working and reference memory errors in the CPF group, indicating an
      abnormal dependence on 5HT systems. Our results indicate that neonatal CPF
      exposures, classically thought to be subtoxic, produce lasting changes in 5HT
      related behaviors that resemble animal models of depression.

PMID- 15866759
TI  - Human neurobehavioral effects of long-term exposure to styrene: a meta-analysis.
AB  - Many reports in the literature suggest that long-term exposure to styrene may
      exert a variety of effects on the nervous system, including increased choice
      reaction time and decreased performance of color discrimination and color
      arrangement tasks. Sufficient information exists to perform a meta-analysis of
      these observations quantifying the relationships between exposure (estimated from
      biomarkers) and effects on two measures of central nervous system function:
      reaction time and color vision. To perform the meta-analysis, we pooled data into
      a single database for each end point. End-point data were transformed to a common
      metric of effect magnitude (percentage of baseline). We estimated styrene
      concentration from biomarkers of exposure and fitted linear least-squares
      equations to the pooled data to produce dose-effect relationships. Statistically
      significant relationships were demonstrated between cumulative styrene exposure
      and increased choice reaction time as well as increased color confusion index.
      Eight work-years of exposure to 20 ppm styrene was estimated to produce a 6.5%
      increase in choice reaction time, which has been shown to significantly increase
      the probability of automobile accidents. The same exposure history was predicted
      to increase the color confusion index as much as 1.7 additional years of age in
      men.

PMID- 15866760
TI  - Historical comparison of perfluorooctanesulfonate, perfluorooctanoate, and other
      fluorochemicals in human blood.
AB  - The purpose of this investigation was to determine whether there has been a
      change in the human blood concentration of perfluorooctanesulfonate (PFOS),
      perfluorooctanoate (PFOA), and five other fluorochemicals since 1974. Blood
      samples were collected in 1974 (serum) and 1989 (plasma) from volunteer
      participants of a large community health study. The study included a total of 356
      samples (178 from each time period). These samples were analyzed by high-pressure
      liquid chromatography/tandem mass spectrometry methods. The median 1974 and 1989
      fluorochemical concentrations, respectively, were as follows: PFOS, 29.5 ng/mL
      vs. 34.7 ng/mL; PFOA, 2.3 ng/mL vs. 5.6 ng/mL; perfluorohexanesulfonate (PFHS),
      1.6 ng/mL vs. 2.4 ng/mL; and N-ethyl perfluorooctanesulfonamidoacetate (PFOSAA),
      less than the lower limit of quantitation (LLOQ; 1.6 ng/mL, vs. 3.4 ng/mL). For N
      methyl perfluorooctanesulfonamidoacetate (M570), perfluorooctanesulfonamide, and
      perfluorooctanesulfonamidoacetate, median serum concentrations in both years were
      less than the LLOQ values (1.0, 1.0, and 2.5 ng/mL, respectively). Statistical
      analysis of 58 paired samples indicated that serum concentrations of PFOS,
      PFOSAA, PFOA, PFHS, and M570 were significantly (p < 0.001) higher in 1989 than
      in 1974. The data from 1989 were then compared with geometric mean fluorochemical
      concentrations of serum samples collected in 2001 from 108 American Red Cross
      adult blood donors from the same region. Except for M570, there were no
      statistically significant (p < 0.05) geometric mean fluorochemical concentration
      differences between the 1989 and 2001 samples. In conclusion, based on this study
      population, PFOS and other serum fluorochemical concentrations have increased
      between 1974 and 1989. Comparison with other regional data collected in 2001 did
      not suggest a continued increase in concentrations since 1989.

PMID- 15866761
TI  - Gliomas and farm pesticide exposure in women: the Upper Midwest Health Study.
AB  - An excess incidence of brain cancer in male farmers has been noted in several
      studies, but few studies have focused on women. The National Institute for
      Occupational Safety and Health Upper Midwest Health Study evaluated effects of
      rural exposures for 341 female glioma cases and 528 controls, all adult (18-80
      years of age) nonmetropolitan residents of Iowa, Michigan, Minnesota, and
      Wisconsin. On average, controls lived longer on farms than did cases. After
      adjusting for age, age group, education, and farm residence, no association with
      glioma was observed for exposure to arsenicals, benzoic acids, carbamates,
      chloroacetanilides, dinitroanilines, inorganics, organochlorines,
      organophosphates, phenoxys, triazines, or urea-based or estrogenic pesticides. An
      increased risk of glioma was observed for carbamate herbicides but was not
      statistically significant (odds ratio = 3.0; 95% confidence interval, 0.9-9.5).
      No association was observed between glioma and exposure to 12 widely used
      specific pesticides, after adjustment for age, age group, education, and any
      other pesticide exposure. These results were not affected after exclusion of
      proxy respondents (43% of cases, 2% of controls). Women were less likely than men
      to have applied pesticides, but more likely to have laundered pesticide
      contaminated clothes. Storing pesticides in the house was associated with a
      statistically non-significant increased risk. Results show that exposure to
      pesticides was not associated with an increased risk of intracranial gliomas in
      women. Other farm-related factors could be etiologic factors and will be
      discussed in future reports.

PMID- 15866762
TI  - Risk-based consumption advice for farmed Atlantic and wild Pacific salmon
      contaminated with dioxins and dioxin-like compounds.
AB  - We reported recently that several organic contaminants occurred at elevated
      concentrations in farmed Atlantic salmon compared with concentrations of the same
      contaminants in wild Pacific salmon [Hites et al. Science 303: 226-229 (2004)].
      We also found that polychlorinated biphenyls (PCBs), toxaphene, dieldrin,
      dioxins, and polybrominated diphenyl ethers occurred at higher concentrations in
      European farm-raised salmon than in farmed salmon from North and South America.
      Health risks (based on a quantitative cancer risk assessment) associated with
      consumption of farmed salmon contaminated with PCBs, toxaphene, and dieldrin were
      higher than risks associated with exposure to the same contaminants in wild
      salmon. Here we present information on cancer and noncancer health risks of
      exposure to dioxins in farmed and wild salmon. The analysis is based on a
      tolerable intake level for dioxin-like compounds established by the World Health
      Organization and on risk estimates for human exposure to dioxins developed by the
      U.S. Environmental Protection Agency. Consumption of farmed salmon at relatively
      low frequencies results in elevated exposure to dioxins and dioxin-like compounds
      with commensurate elevation in estimates of health risk.

PMID- 15866763
TI  - Fluoroquinolone-resistant Campylobacter isolates from conventional and antibiotic
      free chicken products.
AB  - The use of fluoroquinolones (FQs) in poultry production is an important issue in
      public health today. In February 2002, two prominent U.S. poultry companies
      pledged to stop using FQs for flock-wide treatment. One year later, we began a
      survey of Campylobacter isolates on chicken products from these two companies and
      from two producers claiming total abstention from antibiotic use. Using both
      standard isolation methods and new methods modified to enhance detection of FQ
      resistant Campylobacter, we compared rates of FQ-resistant Campylobacter among
      these products. Four major findings were drawn from this study: a) antibiotic
      free brands were not more likely to be contaminated with Campylobacter; b) a high
      percentage of products from the two conventional brands were contaminated with FQ
      resistant Campylobacter (43 and 96%); c) these conventional brands had
      significantly higher odds of carrying resistant strains compared with antibiotic
      free products; and d) supplementing media with FQs increased the sensitivity of
      detecting FQ-resistant strains among mixed populations of Campylobacter, thus
      reducing a bias toward underestimating the prevalence of FQ-resistant
      Campylobacter on samples. These results suggest that FQ resistance may persist in
      the commercial poultry environment in the absence of FQ-selective pressure and
      that these strains contaminate a larger proportion of foods than reported
      previously.

PMID- 15866764
TI  - The application of the Haddon matrix to public health readiness and response
      planning.
AB  - State and local health departments continue to face unprecedented challenges in
      preparing for, recognizing, and responding to threats to the public's health. The
      attacks of 11 September 2001 and the ensuing anthrax mailings of 2001 highlighted
      the public health readiness and response hurdles posed by intentionally caused
      injury and illness. At the same time, recent natural disasters have highlighted
      the need for comparable public health readiness and response capabilities. Public
      health readiness and response activities can be conceptualized similarly for
      intentional attacks, natural disasters, and human-caused accidents. Consistent
      with this view, the federal government has adopted the all-hazards response model
      as its fundamental paradigm. Adoption of this paradigm provides powerful
      improvements in efficiency and efficacy, because it reduces the need to create a
      complex family of situation-specific preparedness and response activities.
      However, in practice, public health preparedness requires additional models and
      tools to provide a framework to better understand and prioritize emergency
      readiness and response needs, as well as to facilitate solutions; this is
      particularly true at the local health department level. Here, we propose to
      extend the use of the Haddon matrix--a conceptual model used for more than two
      decades in injury prevention and response strategies--for this purpose.

PMID- 15866765
TI  - Symptomatic effects of exposure to diluted air sampled from a swine confinement
      atmosphere on healthy human subjects.
AB  - Aerial emissions from a swine house at North Carolina State University's field
      laboratory were diluted to a level that could occur at varying distances downwind
      from a confined animal feeding operation (CAFO) both within and beyond the
      property line, and these emissions were delivered to an environmental exposure
      chamber. The study design consisted of two 1-hr sessions, one in which 48 healthy
      human adult volunteers were exposed to diluted swine air and another in which
      they were exposed to clean air (control). Objective measures of blood pressure,
      temperature, heart rate, respiratory rate, lung function, nasal inflammation,
      secretory immunity, mood, attention, and memory were correlated with objective
      measures of air quality. Ratings of perceived (self-reported) health symptoms
      were also obtained. The mean levels of airborne constituents in the swine air
      condition were hydrogen sulfide (24 ppb), ammonia (817 ppb), total suspended
      particulates (0.0241 mg/m3), endotoxin (7.40 endotoxin units/m3), and odor (57
      times above odor threshold). No statistical differences on objective measures of
      physical symptoms, mood, or attention resulted from the 1-hr exposure to swine
      emissions in the environmental chamber when compared with clean air for healthy
      human volunteers. However, subjects were 4.1 (p = 0.001) times more likely to
      report headaches, 6.1 (p = 0.004) times more likely to report eye irritation, and
      7.8 (p = 0.014) times more likely to report nausea in the swine air
      (experimental) condition than in the control condition. These results indicate
      that short-term exposure in an environmental chamber to malodorous emissions from
      a swine house at levels expected downwind can induce clinically important
      symptoms in healthy human volunteers.

PMID- 15866766
TI  - Ascorbate depletion: a critical step in nickel carcinogenesis?
AB  - Nickel compounds are known to cause respiratory cancer in humans and induce
      tumors in experimental animals. The underlying molecular mechanisms may involve
      genotoxic effects; however, the data from different research groups are not easy
      to reconcile. Here, we challenge the common premise that direct genotoxic effects
      are central to nickel carcinogenesis and probably to that of other metals.
      Instead, we propose that it is formation of metal complexes with proteins and
      other molecules that changes cellular homeostasis and provides conditions for
      selection of cells with transformed phenotype. This is concordant with the major
      requirement for nickel carcinogenicity, which is prolonged action on the target
      tissue. If DNA is not the main nickel target, is there another unique molecule
      that can be attacked with carcinogenic consequences? Our recent observations
      indicate that ascorbate may be such a molecule. Nickel depletes intracellular
      ascorbate, which leads to the inhibition of cellular hydroxylases, manifested by
      the loss of hypoxia-inducible factor (HIF)-1alpha and -2alpha hydroxylation and
      hypoxia-like stress. Proline hydroxylation is crucial for collagen and
      extracellular matrix assembly as well as for assembly of other protein molecules
      that have collagen-like domains, including surfactants and complement. Thus, the
      depletion of ascorbate by chronic exposure to nickel could be deleterious for
      lung cells and may lead to lung cancer. Key words: ascorbate, carcinogenesis,
      collagens, extracellular matrix, hypoxia-inducible transcription factor, metals,
      nickel, protein hydroxylation.

PMID- 15866767
TI  - Two outbreaks of occupationally acquired histoplasmosis: more than workers at
      risk.
AB  - OBJECTIVE: The objective of this study was to determine the etiology and risk
      factors for acute histoplasmosis in two outbreaks in Illinois among laborers at a
      landfill in 2001 and at a bridge reconstruction site in 2003. DESIGN: We
      performed environmental investigations during both outbreaks and also performed
      an analytic cohort study among bridge workers. PARTICIPANTS: Workers at the
      landfill during May 2001 and those at the bridge site during August 2003
      participated in the study. At the landfill, workers moved topsoil from an area
      that previously housed a barn; at the bridge, workers observed bat guano on
      bridge beams. EVALUATIONS/MEASUREMENTS: We defined a case by positive
      immunodiffusion serology, a > or = 4-fold titer rise in complement fixation
      between acute and convalescent sera, or positive urinary Histoplasma capsulatum
      (HC) antigen. Relative risks (RR) for disease among bridge workers were
      calculated using bivariate analysis. RESULTS: Eight of 11 landfill workers (73%)
      and 6 of 12 bridge workers (50%) were laboratory-confirmed histoplasmosis cases.
      Three bridge workers had positive urinary HC antigen. At the bridge, seeing or
      having contact with bats [RR = 7.0; 95% confidence interval (CI), 1.1-43.0], jack
      hammering (RR = 4.0; 95% CI, 1.2-13.3), and waste disposal (RR = 4.0; 95% CI, 1.2
      13.3) were the most significant job-related risk factors for acquiring
      histoplasmosis. CONCLUSIONS: Workers performing activities that aerosolized
      topsoil and dust were at increased risk for acquiring histoplasmosis. Relevance
      to professional and clinical practice: Employees should wear personal protective
      equipment and use dust-suppression techniques when working in areas potentially
      contaminated with bird or bat droppings. Urinary HC antigen testing was important
      in rapidly identifying disease in the 2003 outbreak.

PMID- 15866768
TI  - Public health and economic consequences of methyl mercury toxicity to the
      developing brain.
AB  - Methyl mercury is a developmental neurotoxicant. Exposure results principally
      from consumption by pregnant women of seafood contaminated by mercury from
      anthropogenic (70%) and natural (30%) sources. Throughout the 1990s, the U.S.
      Environmental Protection Agency (EPA) made steady progress in reducing mercury
      emissions from anthropogenic sources, especially from power plants, which account
      for 41% of anthropogenic emissions. However, the U.S. EPA recently proposed to
      slow this progress, citing high costs of pollution abatement. To put into
      perspective the costs of controlling emissions from American power plants, we
      have estimated the economic costs of methyl mercury toxicity attributable to
      mercury from these plants. We used an environmentally attributable fraction model
      and limited our analysis to the neurodevelopmental impacts--specifically loss of
      intelligence. Using national blood mercury prevalence data from the Centers for
      Disease Control and Prevention, we found that between 316,588 and 637,233
      children each year have cord blood mercury levels > 5.8 microg/L, a level
      associated with loss of IQ. The resulting loss of intelligence causes diminished
      economic productivity that persists over the entire lifetime of these children.
      This lost productivity is the major cost of methyl mercury toxicity, and it
      amounts to $8.7 billion annually (range, $2.2-43.8 billion; all costs are in 2000
      US$). Of this total, $1.3 billion (range, $0.1-6.5 billion) each year is
      attributable to mercury emissions from American power plants. This significant
      toll threatens the economic health and security of the United States and should
      be considered in the debate on mercury pollution controls.

PMID- 15866769
TI  - IQ and blood lead from 2 to 7 years of age: are the effects in older children the
      residual of high blood lead concentrations in 2-year-olds?
AB  - Increases in peak blood lead concentrations, which occur at 18-30 months of age
      in the United States, are thought to result in lower IQ scores at 4-6 years of
      age, when IQ becomes stable and measurable. Data from a prospective study
      conducted in Boston suggested that blood lead concentrations at 2 years of age
      were more predictive of cognitive deficits in older children than were later
      blood lead concentrations or blood lead concentrations measured concurrently with
      IQ. Therefore, cross-sectional associations between blood lead and IQ in school
      age children have been widely interpreted as the residual effects of higher blood
      lead concentrations at an earlier age or the tendency of less intelligent
      children to ingest more leaded dust or paint chips, rather than as a causal
      relationship in older children. Here we analyze data from a clinical trial in
      which children were treated for elevated blood lead concentrations (20-44
      microg/dL) at about 2 years of age and followed until 7 years of age with serial
      IQ tests and measurements of blood lead. We found that cross-sectional
      associations increased in strength as the children became older, whereas the
      relation between baseline blood lead and IQ attenuated. Peak blood lead level
      thus does not fully account for the observed association in older children
      between their lower blood lead concentrations and IQ. The effect of concurrent
      blood level on IQ may therefore be greater than currently believed.

PMID- 15866770
TI  - A time-series analysis of air pollution and preterm birth in Pennsylvania, 1997
      2001.
AB  - Preterm delivery can lead to serious infant health outcomes, including death and
      lifelong disability. Small increases in preterm delivery risk in relation to
      spatial gradients of air pollution have been reported, but previous studies may
      have controlled inadequately for individual factors. Using a time-series
      analysis, which eliminates potential confounding by individual risk factors that
      do not change over short periods of time, we investigated the effect of ambient
      outdoor particulate matter with diameter < or = 10 microm (PM10) and sulfur
      dioxide on risk for preterm delivery. Daily counts of preterm births were
      obtained from birth records in four Pennsylvania counties from 1997 through 2001.
      We observed increased risk for preterm delivery with exposure to average PM10 and
      SO2 in the 6 weeks before birth [respectively, relative risk (RR) = 1.07; 95%
      confidence interval (CI), 0.98-1.18 per 50 microg/m3 increase; RR = 1.15; 95% CI,
      1.00-1. 32 per 15 ppb increase], adjusting for long-term preterm delivery trends,
      co-pollutants, and offsetting by the number of gestations at risk. We also
      examined lags up to 7 days before the birth and found an acute effect of exposure
      to PM10 2 days and 5 days before birth (respectively, RR = 1.10; 95% CI, 1.00
      1.21; RR = 1.07; 95% CI, 0.98-1.18) and SO2 3 days before birth (RR = 1.07; 95%
      CI, 0.99-1.15), adjusting for covariates, including temperature, dew point
      temperature, and day of the week. The results from this time-series analysis,
      which provides evidence of an increase in preterm birth risk with exposure to
      PM10 and SO2, are consistent with prior investigations of spatial contrasts.

PMID- 15866771
TI  - Acute respiratory diseases and carboxyhemoglobin status in school children of
      Quito, Ecuador.
AB  - Outdoor carbon monoxide comes mainly from vehicular emissions, and high
      concentrations occur in areas with heavy traffic congestion. CO binds to
      hemoglobin, forming carboxyhemoglobin (COHb), and reduces oxygen delivery. We
      investigated the link between the adverse effects of CO on the respiratory system
      using COHb as a marker for chronic CO exposure. We examined the relationship
      between acute respiratory infections (ARIs) and COHb concentrations in school-age
      children living in urban and suburban areas of Quito, Ecuador. We selected three
      schools located in areas with different traffic intensities and enrolled 960
      children. To adjust for potential confounders we conducted a detailed survey. In
      a random subsample of 295 children, we determined that average COHb
      concentrations were significantly higher in children attending schools in areas
      with high and moderate traffic, compared with the low-traffic area. The
      percentage of children with COHb concentrations above the safe level of 2.5% were
      1, 43, and 92% in low-, moderate-, and high-traffic areas, respectively. Children
      with COHb above the safe level are 3.25 [95% confidence interval (CI), 1.65-6.38]
      times more likely to have ARI than children with COHb < 2.5%. Furthermore, with
      each percent increase in COHb above the safety level, children are 1.15 (95% CI,
      1.03-1.28) times more likely to have an additional case of ARI. Our findings
      provide strong evidence of the relation between CO exposure and susceptibility to
      respiratory infections.

PMID- 15866772
TI  - Time course of gene expression of inflammatory mediators in rat lung after diesel
      exhaust particle exposure.
AB  - Diesel exhaust particles (DEPs) at three concentrations (5, 35, and 50 mg/kg body
      weight) were instilled into rats intratracheally. We studied gene expression at
      1, 7, and 30 days postexposure in cells obtained by bronchoalveolar lavage (BAL)
      and in lung tissue. Using real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR), we measured the mRNA levels of eight genes [interleukin (IL)
      1beta, IL-6, IL-10, iNOS (inducible nitric oxide synthase), MCP-1 (monocyte
      chemoattractant protein-1), MIP-2 (macrophage inflammatory protein-2), TGF-beta1
      (transforming growth factor-beta1), and TNF-alpha (tumor necrosis factor-alpha )]
      in BAL cells and four genes [IL-6, ICAM-1 (intercellular adhesion molecule-1), GM
      CSF (granulocyte/macrophage-colony stimulating factor), and RANTES (regulated
      upon activation normal T cell expressed and secreted)] in lung tissue. In BAL
      cells on day 1, high-dose exposure induced a significant up-regulation of IL
      1beta, iNOS, MCP-1, and MIP-2 but no change in IL-6, IL-10, TGF-beta1, and TNF
      alpha mRNA levels. There was no change in the mRNA levels of IL-6, RANTES, ICAM
      1, and GM-CSF in lung tissue. Nitric oxide production and levels of MCP-1 and MIP
      2 were increased in the 24-hr culture media of alveolar macrophages (AMs)
      obtained on day 1. IL-6, MCP-1, and MIP-2 levels were also elevated in the BAL
      fluid. BAL fluid also showed increases in albumin and lactate dehydrogenase. The
      cellular content in BAL fluid increased at all doses and at all time periods,
      mainly due to an increase in polymorphonuclear leukocytes. In vitro studies in
      AMs and cultured lung fibroblasts showed that lung fibroblasts are a significant
      source of IL-6 and MCP-1 in the lung.

PMID- 15866773
TI  - Overview of aerosolized Florida red tide toxins: exposures and effects.
AB  - Florida red tide is caused by Karenia brevis, a dinoflagellate that periodically
      blooms, releasing its potent neurotoxin, brevetoxin, into the surrounding waters
      and air along the coast of the Gulf of Mexico. Exposure to Florida red tide
      toxins has been associated with adverse human health effects and massive fish and
      marine mammal deaths. The articles in this mini-monograph describe the ongoing
      interdisciplinary and interagency research program that characterizes the
      exposures and health effects of aerosolized Florida red tide toxins
      (brevetoxins). The interdisciplinary research program uses animal models and
      laboratory studies to develop hypotheses and apply these findings to in situ
      human exposures. Our ultimate goal is to develop appropriate prevention measures
      and medical interventions to mitigate or prevent adverse health effects from
      exposure to complex mixtures of aerosolized red tide toxins.

PMID- 15866774
TI  - Natural and derivative brevetoxins: historical background, multiplicity, and
      effects.
AB  - Symptoms consistent with inhalation toxicity have long been associated with
      Florida red tides, and various causal agents have been proposed. Research since
      1981 has centered on a group of naturally occurring trans-fused cyclic polyether
      compounds called brevetoxins that are produced by a marine dinoflagellate known
      as Karenia brevis. Numerous individual brevetoxins have been identified from
      cultures as well as from natural bloom events. A spectrum of brevetoxin
      derivatives produced by chemical modification of the natural toxins has been
      prepared to examine the effects of functional group modification on physiologic
      activity. Certain structural features of natural and synthetic derivatives of
      brevetoxin appear to ascribe specific physiologic consequences to each toxin.
      Differential physiologic effects have been documented with many of the natural
      toxins and derivatives, reinforcing the hypothesis that metabolism or
      modification of toxin structures modulates both the specific toxicity (lethality
      on a per milligram basis) and potentially the molecular mechanism(s) of action. A
      series of naturally occurring fused-ring polyether compounds with fewer rings
      than brevetoxin, known as brevenals, exhibit antagonistic properties and
      counteract the effects of the brevetoxins in neuronal and pulmonary model
      systems. Taken together, the inhalation toxicity of Florida red tides would
      appear to depend on the amount of each toxin present, as well as on the spectrum
      of molecular activities elicited by each toxin. Toxicity in a bloom is diminished
      by the amount brevenal present.

PMID- 15866775
TI  - Inhalation toxicity of brevetoxin 3 in rats exposed for twenty-two days.
AB  - Brevetoxins are potent neurotoxins produced by the marine dinoflagellate Karenia
      brevis. Exposure to brevetoxins may occur during a K. brevis red tide when the
      compounds become aerosolized by wind and surf. This study assessed possible
      adverse health effects associated with inhalation exposure to brevetoxin 3, one
      of the major brevetoxins produced by K. brevis and present in aerosols collected
      along beaches affected by red tide. Male F344 rats were exposed to brevetoxin 3
      at 0, 37, and 237 microg/m3 by nose-only inhalation 2 hr/day, 5 days/week for up
      to 22 exposure days. Estimated deposited brevetoxin 3 doses were 0.9 and 5.8
      microg/kg/day for the low- and high-dose groups, respectively. Body weights of
      the high-dose group were significantly below control values. There were no
      clinical signs of toxicity. Terminal body weights of both low- and high-dose
      group rats were significantly below control values. Minimal alveolar macrophage
      hyperplasia was observed in three of six and six of six of the low- and high-dose
      groups, respectively. No histopathologic lesions were observed in the nose,
      brain, liver, or bone marrow of any group. Reticulocyte numbers in whole blood
      were significantly increased in the high-dose group, and mean corpuscular volume
      showed a significant decreasing trend with increasing exposure concentration.
      Humoral-mediated immunity was suppressed in brevetoxin-exposed rats as indicated
      by significant reduction in splenic plaque-forming cells in both low- and high
      dose-group rats compared with controls. Results indicate that the immune system
      is the primary target for toxicity in rats after repeated inhalation exposure to
      relatively high concentrations of brevetoxins.

PMID- 15866776
TI  - Effects of inhaled brevetoxins in allergic airways: toxin-allergen interactions
      and pharmacologic intervention.
AB  - During a Florida red tide, brevetoxins produced by the dinoflagellate Karenia
      brevis become aerosolized and cause airway symptoms in humans, especially in
      those with pre-existing airway disease (e.g., asthma). To understand these toxin
      induced airway effects, we used sheep with airway hypersensitivity to Ascaris
      suum antigen as a surrogate for asthmatic patients and studied changes in
      pulmonary airflow resistance (R(L) after inhalation challenge with lysed cultures
      of K. brevis (crude brevetoxins). Studies were done without and with clinically
      available drugs to determine which might prevent/reverse these effects. Crude
      brevetoxins (20 breaths at 100 pg/mL; n = 5) increased R(L) 128 +/- 6% (mean +/-
      SE) over baseline. This bronchoconstriction was significantly reduced (%
      inhibition) after pretreatment with the glucocorticosteroid budesonide (49%), the
      beta(2) adrenergic agent albuterol (71%), the anticholinergic agent atropine
      (58%), and the histamine H1-antagonist diphenhydramine (47%). The protection
      afforded by atropine and diphenhydramine suggests that both cholinergic (vagal)
      and H1-mediated pathways contribute to the bronchoconstriction. The response to
      cutaneous toxin injection was also histamine mediated. Thus, the airway and skin
      data support the hypothesis that toxin activates mast cells in vivo. Albuterol
      given immediately after toxin challenge rapidly reversed the bronchoconstriction.
      Toxin inhalation increased airway kinins, and the response to inhaled toxin was
      enhanced after allergen challenge. Both factors could contribute to the increased
      sensitivity of asthmatic patients to toxin exposure. We conclude that K. brevis
      aerosols are potent airway constrictors. Clinically available drugs may be used
      to prevent or provide therapeutic relief for affected individuals.

PMID- 15866777
TI  - Characterization of marine aerosol for assessment of human exposure to
      brevetoxins.
AB  - Red tides in the Gulf of Mexico are commonly formed by the fish-killing
      dinoflagellate Karenia brevis, which produces nine potent polyether brevetoxins
      (PbTxs). Brevetoxins can be transferred from water to air in wind-powered white
      capped waves. Inhalation exposure to marine aerosol containing brevetoxins causes
      respiratory symptoms. We describe detailed characterization of aerosols during an
      epidemiologic study of occupational exposure to Florida red tide aerosol in terms
      of its concentration, toxin profile, and particle size distribution. This
      information is essential in understanding its source, assessing exposure to
      people, and estimating dose of inhaled aerosols. Environmental sampling confirmed
      the presence of brevetoxins in water and air during a red tide exposure period
      (September 2001) and lack of significant toxin levels in the water and air during
      an unexposed period (May 2002). Water samples collected during a red tide bloom
      in 2001 showed moderate-to-high concentrations of K. brevis cells and PbTxs. The
      daily mean PbTx concentration in water samples ranged from 8 to 28 microg/L from
      7 to 11 September 2001; the daily mean PbTx concentration in air samples ranged
      from 1.3 to 27 ng/m(3). The daily aerosol concentration on the beach can be
      related to PbTx concentration in water, wind speed, and wind direction. Personal
      samples confirmed human exposure to red tide aerosols. The particle size
      distribution showed a mean aerodynamic diameter in the size range of 6-12 microm,
      with deposits mainly in the upper airways. The deposition pattern correlated with
      the observed increase of upper airway symptoms in healthy lifeguards during the
      exposure periods.

PMID- 15866778
TI  - Occupational exposure to aerosolized brevetoxins during Florida red tide events:
      effects on a healthy worker population.
AB  - Karenia brevis (formerly Gymnodinium breve) is a marine dinoflagellate
      responsible for red tides that form in the Gulf of Mexico. K. brevis produces
      brevetoxins, the potent toxins that cause neurotoxic shellfish poisoning. There
      is also limited information describing human health effects from environmental
      exposures to brevetoxins. Our objective was to examine the impact of inhaling
      aerosolized brevetoxins during red tide events on self-reported symptoms and
      pulmonary function. We recruited a group of 28 healthy lifeguards who are
      occupationally exposed to red tide toxins during their daily work-related
      activities. They performed spirometry tests and reported symptoms before and
      after their 8-hr shifts during a time when there was no red tide (unexposed
      period) and again when there was a red tide (exposed period). We also examined
      how mild exercise affected the reported symptoms and spirometry tests during
      unexposed and exposed periods with a subgroup of the same lifeguards.
      Environmental sampling (K. brevis cell concentrations in seawater and brevetoxin
      concentrations in seawater and air) was used to confirm unexposed/exposed status.
      Compared with unexposed periods, the group of lifeguards reported more upper
      respiratory symptoms during the exposed periods. We did not observe any impact of
      exposure to aerosolized brevetoxins, with or without mild exercise, on pulmonary
      function.

PMID- 15866781
TI  - The swings and roundabouts of randomized controlled studies in wound healing.

PMID- 15866780
TI  - What Causes Lesions in Sperm Whale Bones?

PMID- 15866779
TI  - Initial evaluation of the effects of aerosolized Florida red tide toxins
      (brevetoxins) in persons with asthma.
AB  - Florida red tides annually occur in the Gulf of Mexico, resulting from blooms of
      the marine dinoflagellate Karenia brevis. K. brevis produces highly potent
      natural polyether toxins, known as brevetoxins, that activate voltage-sensitive
      sodium channels. In experimental animals, brevetoxins cause significant
      bronchoconstriction. A study of persons who visited the beach recreationally
      found a significant increase in self-reported respiratory symptoms after exposure
      to aerosolized Florida red tides. Anecdotal reports indicate that persons with
      underlying respiratory diseases may be particularly susceptible to adverse health
      effects from these aerosolized toxins. Fifty-nine persons with physician
      diagnosed asthma were evaluated for 1 hr before and after going to the beach on
      days with and without Florida red tide. Study participants were evaluated with a
      brief symptom questionnaire, nose and throat swabs, and spirometry approved by
      the National Institute for Occupational Safety and Health. Environmental
      monitoring, water and air sampling (i.e., K. brevis, brevetoxins, and particulate
      size distribution), and personal monitoring (for toxins) were performed.
      Brevetoxin concentrations were measured by liquid chromatography mass
      spectrometry, high-performance liquid chromatography, and a newly developed
      brevetoxin enzyme-linked immunosorbent assay. Participants were significantly
      more likely to report respiratory symptoms after Florida red tide exposure.
      Participants demonstrated small but statistically significant decreases in forced
      expiratory volume in 1 sec, forced expiratory flow between 25 and 75%, and peak
      expiratory flow after exposure, particularly those regularly using asthma
      medications. Similar evaluation during nonexposure periods did not significantly
      differ. This is the first study to show objectively measurable adverse health
      effects from exposure to aerosolized Florida red tide toxins in persons with
      asthma. Future studies will examine the possible chronic effects of these toxins
      among persons with asthma and other chronic respiratory impairment.

PMID- 15866782
TI  - Reliability and accuracy of techniques for surface area measurements of wounds
      and scars.
AB  - The applicability of simple methods to measure the size of pathological skin
      lesions for management and research has been poorly studied to date. The
      interobserver reliability and accuracy (validity) was established for planimetry
      by photography and planimetry by tracing on a transparent sheet in this study.
      Drawings of 25, 50, and 75 cm(2) were created on 3 locations with increasing
      curvature (back, thigh, and forearm) in 20 healthy volunteers. Three
      investigators evaluated the drawings by both planimetry techniques. Both
      techniques showed a good reliability (r >or= 0.82, intraclass correlation) for 25
      cm(2) areas. Planimetry by photography was more reliable than planimetry by
      tracings for the 50 -and 75-cm(2) areas and was more accurate than planimetry by
      tracing for all areas except for the area with the greatest curvature, the
      forearm. The study permits the conclusion that planimetry by photography is more
      suitable for surface area measurements than planimetry by tracing except for
      extremely curved body parts, where it is likely that effects of distortion
      supervene.

PMID- 15866783
TI  - Decreasing foot pressures while implementing topical negative pressure (vacuum
      assisted closure) therapy.
AB  - Over the past generation, there have been a number of significant advances in
      wound healing in general. Unfortunately, much of this has not translated into
      increased success in healing wounds on the sole of the foot. We believe that much
      of this therapeutic disconnect has to do with an inadequate merging of pressure
      off-loading technologies and active wound-healing technologies. This article
      discusses such a merger between removable cast walkers and topical negative
      pressure (also known as vacuum-assisted closure).

PMID- 15866784
TI  - Small fiber neuropathy in diabetes: clinical consequence and assessment.
AB  - Recent findings have shed new light on the role of peripheral nerves in the skin
      and have established a modern concept of cutaneous neurobiology. There is
      bidirectional rather than unidirectional (conveying information from the
      periphery) signaling between central and peripheral nerves and the endocrine and
      immune systems. This interaction is mediated principally by cutaneous small nerve
      fibers and will influence a variety of physiologic and pathophysiologic functions
      central to wound healing, which include cellular development, growth,
      differentiation, immunity, vasoregulation, and leukocyte recruitment. Thus,
      disease of the small fibers in diabetic patients is frequent and may have a
      considerable impact on the predisposition and subsequent wound-healing response
      to foot ulceration. The authors review the basic pathophysiology, clinical
      consequences, and current methods to evaluate somatic and autonomic nerve fiber
      dysfunction and damage.

PMID- 15866785
TI  - Ingrowing toenails: management practices and research outcomes.
AB  - The ingrowing toenail, often seen as a trivial condition, can be a substantial
      source of pain and potential morbidity in high-risk patients. Furthermore, this
      malady is commonly seen by the general practitioner who possesses little training
      in the management of the condition. Compounding the problem is the myriad of
      reported nonsurgical and surgical treatments. This article reviews the topic of
      ingrowing toenails and offers treatment options based on a review of the
      literature.

PMID- 15866786
TI  - Involvement of the sympathetic nervous system in complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS) occasionally develops as a complication of
      limb trauma. Sympathetic neurotransmitter release is compromised in the affected
      limb of at least a subgroup of patients throughout the course of the disorder,
      whereas signs of sympathetic deficit (a warm flushed limb) often evolve into
      signs of sympathetic overactivity (a cool moist limb) due to the development of
      adrenergic supersensitivity. Cross-talk between sympathetic neurotransmitters and
      the sensory neurons that signal pain appears to contribute to CRPS in a subgroup
      of patients. In addition, sympathetic activity may retard normal healing by
      aggravating the vascular disturbances associated with inflammation. Sympathetic
      dysfunction seems to originate from within the central nervous system in patients
      without peripheral nerve injury, possibly in association with chronic activation
      of the "defeat" response associated with inhibitory opioid-mediated pain
      modulation. Fatigue of this inhibitory process may unmask a facilitatory
      influence of arousal on nociceptive transmission in the thalamus and cortex that
      contributes to stress-induced pain.

PMID- 15866787
TI  - Recurring wounds in a diabetic with multiple medical problems: lower extremity
      wound care.
AB  - Acute trauma leading to open wounds in the lower extremity of a patient with
      diabetes mellitus can be life threatening. Diabetes mellitus complicates and
      compromises wound care and tissue repair for several reasons. This case report
      describes the successful wound care treatment modalities used in the care of a 53
      year-old male who presented with diabetes and a full-thickness lower leg wound.

PMID- 15866788
TI  - Chronic nonhealing ulcer of the lower limb with mixed arterio-venous pathology.
AB  - Chronic wounds in which arterial and venous pathology coexist are relatively
      uncommon. The authors report a case of a diabetic lady who presented with
      claudication pain and a chronic nonhealing lower extremity wound of more than 6
      months. In these patients, it is mandatory to treat the arterial insufficiency
      first, and it is also important to avoid compression bandaging, which is advised
      for venous ulcers.

PMID- 15866789
TI  - Microcirculation in the diabetic foot: an update.

PMID- 15866790
TI  - The changing lexicon of wound treatment.

PMID- 15866791
TI  - Is there enough information about foot care among patients with diabetes?
AB  - The United Kingdom has a diabetic population of approximately 1.2 million. It is
      estimated that approximately 15% of all patients with diabetes will develop a
      foot ulcer in their lifetime. Twenty-five percent of all patients with foot
      ulcers will have a major amputation. There have been several publications
      demonstrating a reduction in foot ulcer and amputation rate through a range of
      active educational programs and ways of improving patient awareness of the
      problem. The authors' study attempted to establish the amount of information
      patients with diabetes have about care of their feet. Of 110 patients recruited,
      37 (33%) claimed they had never received any information about foot care. Of
      those who had received advice, approximately half had received information or had
      access to information over the previous 10 years. In the majority of cases,
      information had been given once only. In conclusion, 33% of patients with
      diabetes did not recall receiving any information about foot care.

PMID- 15866792
TI  - Gene therapy in the treatment of lower extremity wounds.
AB  - This article presents a brief overview of the etiology of chronic wounds of the
      lower extremities and their current medical and surgical treatment. Gene therapy
      as a potential tool for treating therapeutically challenging wounds is described
      in terms of the vectors employed in gene transfer, as well as the strategies used
      to promote wound healing. Results from animal model studies, as well as clinical
      trials, are presented.

PMID- 15866793
TI  - Cutaneous tissue engineering and lower extremity wounds (part 1).
AB  - Tissue-engineered skin is a novel therapeutic with which difficult-to-heal lower
      extremity wounds may be treated. Such skins are products of cutaneous tissue
      engineering that provide an alternative for autologous or allogeneic tissue
      transplantation, thereby avoiding problems associated with donor site
      availability, the risk of infection, and scarring. Recently developed tissue
      engineered skin equivalents have shown to be superior in certain ways to
      compression therapy for refractory venous ulcers and acute wounds. These biologic
      products behave similarly to autografts.

PMID- 15866794
TI  - Cost-effectiveness: seeking value for money in lower extremity wound management.
AB  - This article discusses the different methods of evaluating cost in relation to
      the outcomes of treatment, and reviews the evidence of cost-effectiveness (CE) in
      the management of chronic leg ulceration. In essence, the CE argument revolves
      around the need to demonstrate outcomes of treatment in relation to particular
      levels of financial input by the health providers. High CE allows for either the
      same number of patients to be treated more efficiently (at a lower cost) or more
      patients to be treated for the same financial input. A review of medical and
      nursing databases (Medline, Embase, and Cinahl) identified studies of CE of
      dressing materials (n = 8), use of compression therapy (n = 4), and other
      treatments (n = 2). In addition, 5 research groups have undertaken studies to
      evaluate the relative CE of different systems of care. Overall conclusions are
      that modern wound dressings provide a more cost-effective alternative to saline
      gauze, whereas the evidence relating to the use of tissue-engineered skin is less
      clear. The use of compression bandaging is substantially more cost-effective when
      compared with a system of care where compression is not systematically offered.
      The systems that offer compression are not only cost-effective but also lead to
      reductions in absolute cost. The evaluation of CE is likely to become an ever
      increasing part of wound care evaluation as we strive to achieve greater
      efficiency in the use of scarce health resources.

PMID- 15866795
TI  - Burn injuries from radiation.
AB  - Accidental exposure to radiation leading to injury and illness occurs
      notwithstanding safety devices and protocols used for protection. The medical
      management of radiation casualties is a major concern. Radiation effects are
      principally thermal, similar to electrical burn injuries, but with some unique
      systemic expression. The pathological effects of radiation to the skin are known;
      it is often difficult to assess the level of severity, quickly and with accuracy,
      because of the delay between exposure and the appearance of lesions and obscured
      lesions. The severity depends mainly on the nature of the radiation.High-energy
      penetrating radiation causes more irreversible damage than low-energy radiation,
      which penetrates tissues less than the former. A thorough knowledge, high index
      of suspicion, and a team approach are keys to successful management.

PMID- 15866796
TI  - Squamous cell carcinoma in epidermolysis bullosa.
AB  - Epidermolysis bullosa (EB) is a group of inherited blistering disorders that are
      divided into three categories based on the plane of cleavage of the blister, mode
      of inheritance, and the presence or absence of scars. Squamous cell carcinoma
      developing in epidermolysis bullosa is rare and presents a therapeutic dilemma.
      The authors report a case of congenital epidermolysis bullosa with locally
      advanced squamous cell carcinoma.

PMID- 15866797
TI  - Transdermal CO2 application in chronic wounds.
AB  - Chronic wounds are a challenge to treatment. In this retrospective study, the
      effect of transdermal CO2 application on wound healing in chronic ulcers was
      investigated and compared to the effect of CO2 on acute surgical wounds. Eighty
      six patients (52 females and 34 males) with chronic wounds of different origin
      except arterial occlusive disease were included. In addition, 17 patients (5
      females, 12 males) with wide excision wounds after surgical therapy of acne
      inversa were considered. The indication for CO2 application was a wound at risk
      for infection. Treatment was performed with a Carboflow device once daily for 30
      to 60 minutes. There was clinical evidence of improvement of granulation and
      reduction of discharge and malodor within 1 week of treatment in both chronic and
      acute wounds. Only 9 patients, all diabetics, needed an additional systemic
      antibiosis. The treatment was well tolerated. No adverse effects have been noted.
      Transdermal CO2 application is a useful method to reduce the risk of infection
      and improve wound healing in both chronic and certain acute wounds. Systematic
      prospective trials are needed.

PMID- 15866798
TI  - Extra-articular pigmented villonodular synovitis.
AB  - Villonodular synovitis are a group of idiopathic lesions that affect the synovial
      surfaces of joints, tendon sheaths, and bursae, causing tumor-like lesions.
      Pigmented villonodular synovitis rarely affects the tendon sheaths; its
      occurrence in extra-articular sites is uncommon. This case is presented for the
      rarity of occurrence. The literature is also reviewed.

PMID- 15866799
TI  - Outcomes.

PMID- 15866800
TI  - Skin substitutes and wound treatment.

PMID- 15866801
TI  - Evans (1966) exchange and the skin in the light of vacuum-assisted closure, yoga,
      and maggots.

PMID- 15866802
TI  - Gabapentin-induced generalized cutaneous small-vessel leukocytoclastic
      vasculitis.

PMID- 15866803
TI  - Wound outcomes: the utility of surface measures.
AB  - The value of using quantitative measures to follow the progress of wound healing
      is well recognized. However, several methods are in use, and the best way to do
      this is not always clear from the literature. This article describes the
      advantages of the linear healing parameter and the disadvantages of the area- and
      volume-based parameters. The shapes and sizes of wounds influence area- and
      volume-based parameters, hence these will give biased comparisons. Healing rates
      based on the linear parameter are independent of initial wound size or shape, and
      they allow unbiased comparisons within and across studies. A formula for
      predicting healing time from measurements early in the healing course is
      presented and discussed. Less precise linear healing measurements that are easy
      to obtain, and that are as valid as the more precise measurements, are also
      described.

PMID- 15866804
TI  - A review of the principles and use of lasers in lower limb problems.
AB  - Lasers present a unique light source with many clinical uses including a number
      of applications relevant to the lower extremity. In this article, the basic
      principles of lasers and their interactions with tissue will be reviewed. The
      article examines laser applications in skin and vascular disease including wound
      healing. The principles of laser safety are discussed, and relevant future
      developments are considered.

PMID- 15866805
TI  - Wound healing potential of Pterocarpus santalinus linn: a pharmacological
      evaluation.
AB  - The need for new therapeutics for wound healing has encouraged the drive to
      examine the nature and value of plant products. Ayurveda, the Indian traditional
      system of medicine, mentions the values of medicinal plants for wound healing.
      One of these is Pterocarpus santalinus. This article describes a pharmacological
      study to evaluate its toxicity as well as wound-healing potential in animal
      studies. Powder made from the wood of the P. santalinus tree was used to make up
      an ointment in a petroleum jelly base. No toxic effects were observed in 72
      hours. Studies were done on punch and burn wound models on normal and diabetic
      rats using the test ointment, untreated and vehicle controls, and standard
      therapy. Physical and biochemical measurements were made. The test ointment
      treated wounds healed significantly faster. On healing, collagenesis and
      biochemical measurements yielded supportive data. These studies permit the
      conclusion that the P. santalinus ointment is safe and effective in treating
      acute wounds in animal models.

PMID- 15866806
TI  - Analysis of skin wound images using digital color image processing: a preliminary
      communication.
AB  - This article presents the use of digital image processing using hue, saturation,
      and intensity measurements as a technique for the color analysis of chronic
      wounds on the skin. An adaptive spline technique was used to segment the wound
      boundary in the images of venous leg ulcers. This technique was further used to
      approximate the position of venous leg ulcers. The amount of slough within the
      wound site was quantified using the software developed and was compared with a
      grading system based on visual inspection by an experienced clinician, and the
      results were compared by deriving Kappa (K) statistic. There was moderate
      agreement over all grades between the computer and clinician. At lower grades 1
      and 2, there was excellent agreement. The results from this preliminary study
      suggest that this analytical technique has the potential to image process chronic
      skin wounds.

PMID- 15866807
TI  - An audit of foot infections in patients with diabetes mellitus following renal
      transplantation.
AB  - Foot lesions in postrenal transplant diabetics are often overlooked and hence
      underestimated. An audit of patients attending the authors' department was done.
      They reviewed the case notes to assess the presentation, clinical profiles, and
      outcomes of foot infections in patients with diabetes mellitus who received renal
      transplants at their center. Medical records of 192 diabetic foot patients were
      assessed, of which 8.8% (n = 17) had a history of previous renal transplantation
      for diabetic nephropathy. All 17 patients had noninsulin-dependent diabetes of
      mean duration of 16.2 years (range 7-27 years). Common complications and risk
      factors were studied. Mean duration to development of foot lesions in renal
      allograft recipients was 19.7 months (range 6-84 months). The big toe was the
      most common site of infection. Neuropathy and poor foot care appear to be
      important factors in the development of these foot lesions. Escherichia coli was
      the predominant organism on pus culture. Thirty-eight percent of patients needed
      major amputations; absence of an intact distal vascular tree was associated with
      a high major amputation rate. Two patients expired due to foot-related
      septicemia, and healing occurred in the remainder. Mean hospitalization time was
      32.7 days. Most patients required more than one admission. The study emphasizes
      the need for greater attention to lower extremity complications in this patient
      group.

PMID- 15866808
TI  - An audit of lower extremity complications in octogenarian patients with diabetes
      mellitus.
AB  - Podiatric pathology is common in the elderly patient population per se. Whether
      the presence of diabetes mellitus in the elderly imposes an additional risk for
      podiatric problems is questionable. The purpose of this study was to determine if
      the prevalence of podiatric problems in octogenarian diabetic patients differed
      from that found in a similarly aged group of nondiabetic patients. For this
      study, the prevalence of lower extremity complications in octogenarian patients
      (age 80) with diabetes and without diabetes was estimated using data from the
      1996 through 2002 National Hospital Discharge Survey. The diabetic octogenarian
      patients had twice the risk for developing an ulcer; 3 times the risk of
      developing a foot abscess, and a 4-fold risk of developing osteomyelitis.
      Furthermore, the octogenarian diabetic patient is nearly twice as likely to
      undergo ulceration debridement and 3 to 5 times more likely to have a lower leg
      amputation, toe amputation, or any amputation. The incidence of amputations,
      ulcerations, and other serious conditions is significantly higher in the diabetic
      group compared to normal age-matched control patients. This study shows that in
      the octogenarian patient the presence of diabetes imposes an additive risk for
      complications.

PMID- 15866809
TI  - Sciatic nerve schwannoma.
AB  - Schwannomas are benign tumors of the nerve sheath, commonly seen in the
      vestibular nerve. Although they are common in the head and neck areas, their
      occurrence in extra-cranial locations is rare. We report a case of a sciatic
      nerve schwannoma and review the literature.

PMID- 15866810
TI  - Buried chip skin grafting in neuropathic diabetic foot ulcers following vacuum
      assisted wound bed preparation: enhancing a classic surgical tool with novel
      technologies.
AB  - In patients with diabetes mellitus, complications such as polyneuropathy and
      peripheral angiopathy inevitably lead to diabetic foot complications including
      foot ulcers, gangrene, and osteoarthropathy. These conditions necessitate minor
      or major amputation as part of treatment. In patients with Charcot's arthropathy
      and predominant neuropathy, recurrent foot ulcers are common in areas of high
      pressure. Such high pressure is caused by the degrading of the architecture of
      the foot and inadequate footwear. These patients are a clinical challenge. A
      select group of such patients may benefit from free surgical tissue transfer,
      though free or local flap surgery is often difficult or even impossible owing to
      an impaired arterial circulation. In such wounds, surgical debridement followed
      by skin grafts often fail due to bacterial burden in the wounds. To circumvent
      these problems, the authors developed a therapeutic approach using buried chip
      skin grafting to close granulation wound beds in diabetic feet. Locally applied
      vacuum therapy (VAC) for wound bed preparation of chronic, nonresponsive foot
      ulcers and subsequent grafting using the burying technique with a minute fraction
      of skin was used. Firm closure was achieved. The closed wound was resistant to
      mechanical irritation.

PMID- 15866811
TI  - Wound healing--are we making strides?

PMID- 15866812
TI  - Whither progress in the diabetic foot--clinical and research?

PMID- 15866813
TI  - Pressure offloading and "advanced" wound healing: isn't it finally time for an
      arranged marriage?

PMID- 15866814
TI  - Minimally invasive treatment for varicose veins: a review of endovenous laser
      treatment and radiofrequency ablation.
AB  - Varicose veins are a common problem, conventionally treated by an operation.
      Within the last few years, minimally invasive techniques have been developed as
      alternatives to surgery in an attempt to reduce morbidity and improve recovery
      time. Radiofrequency ablation and endovenous laser ablation are the most
      promising of these new techniques. This review article looks at the evidence for
      these techniques and the clinical experience to date and discusses their role in
      the future treatment of varicose veins.

PMID- 15866815
TI  - The venous ulcer and the superficial venous reflux.
AB  - The management of venous ulcers must take into account the many aspects of the
      pathology and, overall, the hemodynamic patterns of reflux and the clinical
      pictures correlated. The most frequent model is represented by a superficial
      venous reflux that may be successfully treated by surgery with a very high
      percentage of ulcer healing. Compared to compression therapy, surgery allows a
      minor percentage of recurrence. Sclerotherapy may represent a valid alternative.
      The meaning and the treatment of incompetent perforating veins is controversial,
      but the poor results of conservative treatment justify the disconnection of large
      perforators in addition to ablation of saphenous reflux.

PMID- 15866816
TI  - Inflammation and wound healing: the role of bacteria in the immuno-regulation of
      wound healing.
AB  - Wound healing is a sequence of complex events, an imbalance of which can result
      in a failure of the wound to heal, with significant implications for patients and
      health care services alike. Although the exact mechanism that underlies these
      events is not fully understood, inflammatory processes and the innate immune
      system play a vital role, not only in normal wound healing but also in the
      pathophysiology of delayed wound healing. These defense mechanisms are affected
      by underlying disease states and medical conditions, for example, diabetes,
      venous insufficiency, and the inflammation associated with acute trauma.
      Importantly, however, these processes are also modulated in health by bacteria
      within the wound. This article examines the role of the mediators of inflammation
      involved in the wound-healing process and discusses the function of these
      mediators when normal healing fails. The reaction of the wound to bacterial
      contamination and the effect of bacteria on wound healing are also discussed.

PMID- 15866817
TI  - A hospital-based survey of risk factors for diabetic foot ulceration in northern
      Thailand.
AB  - Ulceration of the foot is found more commonly in patients with diabetes mellitus
      than those without it. Foot ulcers affect the lives of patients in many ways, and
      though good care can be defined, loss of limb is a common occurrence in this
      patient group. Therefore, early detection of the foot at risk for foot ulceration
      is of paramount importance. Many risk factors for this type of ulcer have been
      previously reported such as neuropathy, deformity of the foot, arterial
      occlusion, and poor glycemic control. The authors conducted a hospital-based
      survey in patients attending a hospital diabetic clinic to establish a baseline
      database and found that the percentages of sensory neuropathy, history of
      claudication and poor glycemic control were 19.2%, 5.7%, and 79.7%, respectively.
      This suggests the need to establish good diabetic control and health education
      for our patient population.

PMID- 15866818
TI  - Deep infection after ilioinguinal node dissection: vacuum-assisted closure
      therapy?
AB  - Wound infection rates after ilioinguinal node dissection are high; 9% to 16% have
      been reported. The authors report a patient who underwent an ilioinguinal node
      dissection for a regional metastasized melanoma. Unfortunately, a deep wound
      infection occurred with extensive skin necrosis and production of abundant wound
      fluid (750 cc daily). Despite 6-daily dressings, the wound deteriorated,
      necessitating further operative debridement. In theatre, the authors failed to
      identify the lymphatic fistula and therefore were unable to close it. In
      accordance with literature on treatment of groin infections after vascular
      prosthesis, vacuum-assisted closure (VAC) therapy was started. After 11 days of
      VAC therapy, the lymphatic leakage completely stopped. Concurrent successful
      management of the wound with split skin graft therapy led to a complete closure
      of the wound. The treatment was not painful, changes of the sponge could be done
      in the ward, and there were no complications.

PMID- 15866819
TI  - The clinical evaluation of Pterocarpus santalinus Linn. Ointment on lower
      extremity wounds--a preliminary report.
AB  - Pterocarpus santalinus is described in the Ayurveda for its wide spectrum of
      medicinal properties including wound healing. Previously the authors reported
      animal studies that demonstrated that an ointment made from the bark of this tree
      was effective without any toxic effects. They used the same ointment in 6 cases
      of lower extremity wounds. Healing was observed in all wounds. The study was not
      controlled, the findings are presented here as case studies. Further studies are
      planned to develop a wound healing ointment from a locally available and
      inexpensive plant.

PMID- 15866820
TI  - New frontiers in wound healing?

PMID- 15866821
TI  - Changing perspectives in diabetic foot ulcer management.
AB  - Diabetic foot ulceration is a serious complication of diabetes mellitus; it is
      the cause of more than half of nontraumatic lower limb amputations. Diabetic foot
      ulcers are the major cause of hospital admission for diabetic patients. Treatment
      costs are high. There have been advances in managing diabetic foot ulceration
      with the development of new dressings, growth factors, skin substitutes, and
      other novel approaches to stimulating wound healing. The management of vascular
      disease in the patient with diabetes mellitus is an essential and important
      consideration. However, the need for a multidisciplinary team to provide good
      foot care to diabetic patients is still vital for the prevention and treatment of
      diabetic foot ulceration.

PMID- 15866822
TI  - Measurements of transcutaneous oxygen pressure and changes in blood rheology as
      markers of prognosis of critically ischemic limb in diabetes mellitus patients.
AB  - The aims of this study were to compare variations of the transcutaneous oxygen
      pressure (TcPO(2)) and blood rheology in diabetic patients. Diabetic patients
      with critical limb ischemia were compared with those who were either asymptomatic
      or had mild peripheral vascular disease (PVD). The results showed a significant
      decrease in TcPO(2) in patients with critical limb ischemia. Low shear rate blood
      viscosity, red blood cell (RBC) aggregation, plasma viscosity, and fibrinogen
      level were significantly higher in the group with critical severe limb ischemia.
      The group with critical limb ischemia was subdivided on the basis of clinical
      outcomes after 1 year and the prognostic values of these measurements examined. A
      TcPO(2) value of 10 mm Hg was associated with a positive predictive value of 94%.
      RBC aggregation index and fibrinogen levels offered positive predictive values of
      89% and 88%, respectively, when cut off values were derived from means + 1 SD of
      same parameters in patients with asymptomatic or mild PVD. TcPO(2) is useful to
      follow the deterioration of diabetics with critical limb ischemia.

PMID- 15866823
TI  - A case-control study of the risk factors for toe amputation in a diabetic
      population.
AB  - Toe amputations are becoming more prevalent in the diabetic population. To
      prevent toe amputations, those individuals with the highest risk must be
      identified prior to developing a precipitating event. There are obvious risk
      factors for toe amputations, such as digital deformity, diabetic neuropathy, and
      ischemia. Other, less obvious, systemic comorbidities may be linked to toe
      amputations. This study also shows that gender plays a significant role as a risk
      factor for toe amputation. A foot infection, foot abscess, osteomyelitis,
      diabetic retinopathy, and diabetic nephropathy were also significant risk factors
      for toe amputations. This suggests a significant relationship between these
      complications and comorbidities that put these individuals at a higher risk for
      toe amputations.

PMID- 15866824
TI  - Use of herbal medicines in wound healing: a perspective paper.
AB  - Healing of chronic lower extremity wounds is a global problem, especially in the
      developing world where it is often only folk and traditional medicine that can be
      afforded. In the structured health services of the developed world, there are
      usually a wider range of possible therapies. In India, traditional medicines
      flourish in parallel with Western systems, and those who treat wounds may use the
      expertise of more than one system. Ayurveda is a traditional system that has
      evolved in India over centuries using especially native plant sources as
      remedies. Like many Asian systems, its theoretical basis concerns balance and
      energy in the individual. In this perspective paper, the author advocates
      awareness of plant products available for wound healing and a study of the extent
      of their utilization. They must be developed for safe use and their efficacy
      reviewed, taking into account cure well-being and patient satisfaction as well as
      cost. Developing a list of products and classifying them appropriately is a
      beginning for such studies.

PMID- 15866825
TI  - Plant medicines of Indian origin for wound healing activity: a review.
AB  - Research on wound healing drugs is a developing area in modern biomedical
      sciences. Scientists who are trying to develop newer drugs from natural resources
      are looking toward the Ayurveda, the Indian traditional system of medicine.
      Several drugs of plant, mineral, and animal origin are described in the Ayurveda
      for their wound healing properties under the term Vranaropaka. Most of these
      drugs are derived from plant origin. Some of these plants have been screened
      scientifically for the evaluation of their wound healing activity in different
      pharmacological models and patients, but the potential of most remains
      unexplored. In a few cases, active chemical constituents were identified. Some
      Ayurvedic medicinal plants, namely, Ficus bengalensis, Cynodon dactylon,
      Symplocos racemosa, Rubia cordifolia, Pterocarpus santalinus, Ficus racemosa,
      Glycyrrhiza glabra, Berberis aristata, Curcuma longa, Centella asiatica,
      Euphorbia nerifolia, and Aloe vera, were found to be effective in experimental
      models. This paper presents a limited review of plants used in Ayurvedic
      medicine.

PMID- 15866826
TI  - Nonhealing wounds--a therapeutic dilemma.
AB  - Chronic wounds of the lower extremity are a therapeutic dilemma. In India,
      chronic wounds are caused by factors other than impaired circulation and
      diabetes, which account for most of this clinical problem in Western societies. A
      study of 2 topical agents, placental extract and phenytoin powder, is presented
      in this paper. One hundred fifty patients were randomly assigned to these
      treatments or to saline dressings (control). It was observed that patients
      receiving active topical treatments responded better than those in the control
      group. The importance of this finding should be viewed with the perspective that
      these topical treatments are inexpensive and easily available in India. The study
      also piloted measurements of angiogenic responses in 1 group, and the findings
      encourage further exploration with the technique and topical agent.

PMID- 15866827
TI  - A retrospective study of necrotising fasciitis.
AB  - Necrotising fasciitis (NF) is an unusual though well-described soft tissue
      infection of the deeper tissues resulting in a progressive synergistic bacterial
      gangrene. In a small retrospective study in a single center, an association was
      observed between NF and diabetes, age, peripheral arterial disease, and high
      mortality.

PMID- 15866828
TI  - The International Journal of Lower Extremity Wounds.

PMID- 15866829
TI  - Cutaneous wound healing: myofibroblastic differentiation and in vitro models.
AB  - Wound healing is an interactive, dynamic 3-phased process. During the formation
      of granulation tissue, many fibroblastic cells acquire some morphological and
      biochemical smooth muscle features and are called myofibroblasts. Myofibroblasts
      participate in both granulation tissue formation and remodeling phases. Excessive
      scarring, which is a feature of impaired healing, is a serious health problem
      that may affect the patient's quality of life. The treatment costs of such
      lesions are high, and often, the results are unsatisfactory. To understand the
      wound healing process better and to promote improvement in human healing, models
      are needed that can predict the in vivo situation in humans. In vitro models
      allow the study of cell behavior in a controlled environment. Such modeling
      partitions and reduces to small scales behavior perceived in vivo. This article
      is focused on "fibroblasts". In vitro models to study wound healing, the role of
      (myo)fibroblasts, and skin reconstruction in tissue replacement and promotion of
      wound healing are discussed.

PMID- 15866830
TI  - An audit of Keller arthroplasty and metatarsophalangeal joint arthrodesis from
      national data.
AB  - Chronic interphalangeal ulcerations of the great toe are a frequent complication
      in neuropathic diabetic feet. While total contact casting is usually effective as
      a first-line treatment, some ulcers continue and present substantial management
      challenges. The objective of this study was to examine the National Hospital
      Discharge Survey in order to identify links between preexisting medical
      conditions and lower extremity pathology in patients undergoing a Keller
      arthroplasty. Those who received a Keller arthroplasty were more likely to have
      diabetes mellitus (odds ratio [OR] = 4.00, 95% confidence interval [CI]: 3.73
      4.30, P = .0001), diabetic neuropathy (OR = 3.80, 95% CI: 3.48-4.15, P = .0001),
      coronary artery disease (OR = 1.78, 95% CI: 1.57-2.03), or peripheral vascular
      disease (PVD) (OR = 2.06, 95% CI: 1.49-2.84, P = .0001). Keller arthroplasty
      patients were less likely to have a foot abscess (OR = 0.44, 95% CI: 0.39-0.50, P
      = .0001) or hammer toe deformity (OR = 0.60, 95% CI: 0.57-0.63, P = .0001), but
      more likely to have a foot wound or ulcer (OR = 2.62, 95% CI = 2.44-2.82, P =
      .0001), bunions (OR = 4.52, 95% CI: 4.26-4.80, P = .0001), and osteomyelitis (OR
      = 2.65, 95% CI: 2.41-2.92, P = .0001). Hallux limitus or rigidus in a diabetic
      patient with neuropathy, peripheral vascular disease, and poor healing subjects
      this patient to a higher risk of ulceration, infection, and amputation. This
      study shows that this procedure is being performed in the diabetic population
      with attendant complications.

PMID- 15866831
TI  - Laser Doppler imaging in the investigation of lower limb wounds.
AB  - Good blood supply is a primary determinant for the healing of acute and chronic
      wounds alike. Chronic wounds commonly occur in the lower extremity in man.
      Scientists are forever looking for objective techniques with which tissue
      perfusion may be measured with accuracy. Laser Doppler imaging is a very useful
      technique for measuring microvascular perfusion in wounds because it involves no
      contact and produces a color image representing flow distribution over an area of
      tissue. In this article, the authors discuss its application to the assessment of
      lower limb wounds, and they review published studies in which it has been used to
      investigate a range of wound types. This review examines the study of healing
      mechanisms, treatment effects, risk prediction, healing potential, and underlying
      pathology. It also considers areas in which laser Doppler imaging is still to be
      exploited fully.

PMID- 15866832
TI  - Analysis of variance (ANOVA) models in lower extremity wounds.
AB  - Consider a study in which 2 new treatments are being compared with a control
      group. One way to compare outcomes would simply be to compare the 2 treatments
      with the control and the 2 treatments against each using 3 Student t tests (t
      test). If we were to compare 4 treatment groups, then we would need to use 6 t
      tests. The difficulty with using multiple t tests is that as the number of groups
      increases, so will the likelihood of finding a difference between any pair of
      groups simply by change when no real difference exists by definition a Type I
      error. If we were to perform 3 separate t tests each at alpha = .05, the
      experimental error rate increases to .14. As the number of multiple t tests
      increases, the experiment-wise error rate increases rather rapidly. The solution
      to the experimental error rate problem is to use analysis of variance (ANOVA)
      methods. Three basic ANOVA designs are reviewed that give hypothetical examples
      drawn from the literature to illustrate single-factor ANOVA, repeated measures
      ANOVA, and randomized block ANOVA. "No frills" SPSS or SAS code for each of these
      designs and examples used are available from the author on request.

PMID- 15866833
TI  - An uncommon sighting--lupus vulgaris of the foot.
AB  - Lupus vulgaris (LV)is a progressive form of cutaneous tuberculosis (TB)that may
      occur in a patient with a moderate or high degree of immunity. The incidence of
      LV has declined with that in TB; it is relatively uncommon even in developing
      countries. LV commonly presents in the head and neck regions as flat plaques.
      Variants of LV form huge, soft, tumor-like forms with deep tissue and cartilage
      destruction resulting in deformities. The authors report a case of LV in a
      patient who presented with an ulcero-proliferative growth in the lower extremity,
      mimicking a malignancy.

PMID- 15866834
TI  - Some problems of the lower extremity in patients with spinal cord injuries.
AB  - Spinal cord injury (SCI) is devastating, leaving patients wholly or partly
      paralyzed. Health care providers who care for SCI patients during the acute or
      chronic phases are faced with different phenomena in the lower extremities of
      these subjects. In this article, the authors review the relevant changes
      associated with SCI. Preventive measures of these medical complications are
      directed according to the specific cause. Early comprehensive rehabilitation
      carried out by a specialized team prevents complications while enhancing
      functional gains.

PMID- 15866835
TI  - The role of vascular endothelial growth factor in wound healing.
AB  - Revascularization of damaged tissue is a necessary part of wound healing. With
      unregulated or insufficient vessel growth, healing is delayed or pathological.
      Angiogenesis is regulated by expression of a variety of vascular growth factors
      and modulators, the most widely expressed and critical of which is vascular
      endothelial growth factor (VEGF). This protein is secreted by tissues in response
      to ischemic and inflammatory stimuli and results in endothelial migration,
      proliferation, and increased vascular permeability. The regulation of VEGF
      expression during wound healing is of considerable importance since angiogenesis
      appears to be disturbed in abnormally healing wounds. This paper describes the
      current state of knowledge of VEGF expression in wounds, regulation of
      expression, control of isoform specificity, and the effects of VEGF expression on
      blood vessels as they grow in wound healing, as understood from many different
      pathological paradigms.

PMID- 15866836
TI  - The end of a great summer.

PMID- 15866837
TI  - The role of skin hardness, thickness, and sensory loss on standing foot power in
      the development of plantar ulcers in patients with diabetes mellitus--a
      preliminary study.
AB  - This article presents the results of a study on patients with diabetic neuropathy
      to find the relationships between the foot pressures characterized by power ratio
      (PR), foot sole hardness (Shore values), and foot sole soft tissue thickness. The
      results showed that the increase in PR values for diabetic patients in the upper
      sensation loss levels (S = 7.5 to 10 g) compared to the corresponding increase in
      lower sensation loss (S=3 to 4.5 g)were of the order of 5 times in the lateral
      heel and big toe, respectively, and 4 times in the first metatarsal head regions.
      The increase in PR values for diabetic patients in the upper Shore value regions
      (30 to 40) compared to the corresponding increase in lower Shore value regions
      (20 to 30) were of the order of 3.4 times in lateral heel and 2.4, 2.0, and 2.3
      times in the first, second, and lateral metatarsal head regions, respectively. At
      sites contiguous to frank ulcers for foot sole hardness (Shore values of 50) at
      sensation level > 10 g PR was as high as 59, and foot sole thickness values were
      also greater than the corresponding normal values. The study shows all measured
      parameters may play a part in the development of plantar ulcers.

PMID- 15866838
TI  - A clinical investigation on the characteristics and outcomes of treating chronic
      lower extremity wounds using the tissuetech autograft system.
AB  - The application of tissue engineering technology to wound healing has resulted in
      the development of a number of "living skin equivalents." These have become a
      viable option in the treatment of chronic, nonhealing wounds. Such wounds present
      a major cost burden as well as increased morbidity and mortality. Unique among
      skin tissue engineering technology is the TissueTech autograft system, as it
      incorporates an autologous dermal substitute-Hyalograft 3D-and an autologous
      epidermal replacement, Laserskin autograft. Each includes a matrix of a
      hyaluronic acid ester to promote cellular migration and graft take.

PMID- 15866839
TI  - Therapeutic ultrasound in lower extremity wound management.
AB  - In medical practice, ultrasound (US) is used for diagnosis and therapy. High
      frequency (1-4 MHz) and low-frequency (20-120 KHz) therapeutic US are relevant to
      wound healing. The heating effects of high-frequency US are important, whereas
      the mechanical effects of low-frequency US must be considered. The physiological
      effects of low-frequency US include metabolic enhancement, perfusion, wound
      cleansing, and the acceleration of wound granulation. The therapeutic efficacy of
      US depends on dose (W/cm (2) time)and dosage (frequency of application, series).
      At adequate doses, high-frequency and low-frequency therapeutic US induce in
      vitro cell proliferation; protein synthesis; and the production of cytokines by
      fibroblasts, osteoblasts, and monocytes. The mechanical effects of low-frequency
      US cause transient cavitation in wound surfaces for soft and smooth wound
      cleaning, ulcer debridement, and the stimulation of granulation. These effects
      can be determined in clinical studies, though the quality of the studies done so
      far and of the evidence of the usefulness of US is poor. Nevertheless, high
      frequency and low-frequency US may be reasonable options in the management of
      chronic wounds.

PMID- 15866840
TI  - Crossover designs in lower extremity wounds.
AB  - In a basic AB/BA crossover trial, patients are randomly assigned to receive
      either treatment A in the first period followed by treatment B in the second
      period, or treatment B in the first period followed by treatment A in the second
      period. Treatment periods are separated by a suitable washout period that is long
      enough for the treatment effect from the first period to have no residual effect
      to the second treatment period. The AB/BA crossover trial has many advantages
      and, when used appropriately, provides an efficient means for comparing 2
      treatments. If applied and conducted inappropriately, the AB/BA crossover design
      has fatal flaws. The objective of this article is to introduce the AB/BA
      crossover trial and to present some of the issues surrounding crossover trials.
      The crossover trial, when properly implemented and analyzed, remains a valid and
      efficient design alternative to the parallel group design and should not be
      abandoned as has been suggested by the FDA. Crossover studies have an advantage
      over parallel studies, for example, elimination of between-subject variability,
      more statistical power because of paired comparisons, and reduced sample sizes to
      achieve a specified power. Although a test for carryover would be desirable, at
      present there is no widely recognized method for doing this, and some experts
      feel that no method can be reliable.

PMID- 15866841
TI  - Management of plantar ulcers in Hansen's disease.
AB  - Plantar ulcers occur in patients with Hansen's disease not because of the disease
      but because of its neuropathic effects on the skin over the feet. This enhances
      the risk of trauma to patients' feet, leading to the development of ulcers. This
      short article reviews the current management of leprosy on the basis of World
      Health Organization guidelines and the complexities of plantar ulceration in such
      patients. A guide to its management and prevention is also discussed.

PMID- 15866842
TI  - Chronic lower limb ulcer? No--chloroma!
AB  - Extra medullary deposits are often associated with myeloproliferative disorders,
      especially with myeloid neoplasia. These are called granulocytic sarcoma,
      aleukemic leukemia cutis, myeloblastoma, chloroleukemia, extra-medullary myeloid
      tumor, and chloroma. They commonly present in the bone, periosteum, soft tissue,
      lymph nodes, and the skin but can occur anywhere. The authors present their
      experience with a patient with no history of neoplasm presented with a nonhealing
      ulcer of the lower limb that was a chloroma associated with chronic myeloid
      leukemia.

PMID- 15866843
TI  - Mycetoma leg a--case report.
AB  - One rare and peculiar result of repeated minor trauma to the leg is Madura foot.
      Caused by fungi or fungus-like bacteria, Madura foot is found mainly in the
      tropics. A report of a classic case with chronic indurated swelling involving the
      leg and a discharge of yellowish granules is presented. The case is reported to
      highlight the fact that though Maduramycosis needs prolonged intensive
      antibacterial chemotherapy, even extensive disease can be successfully managed
      with conservative therapy.

PMID- 15866844
TI  - Surgery in congential lymphedema: a follow-up of 50 years.
AB  - Surgical methods have been widely used in the past to treat patients with
      congential lymphedema. There are only scant data in recent literature about the
      long-term outcome of these mostly historical methods. On the other hand, the
      subject is not only of interest to those concerned with the history of medicine
      but also may raise a couple of questions about treating such patients today. The
      authors report on a 77-year-old female patient with congential lymphedema with a
      50-year follow-up after lymphedema resection and focus on practical problems of
      bandaging today.

PMID- 15866846
TI  - World Union of Wound Healing Societies.

PMID- 15866845
TI  - Seasonal perspectives.

PMID- 15866847
TI  - Leg ulcers and pain: a review.
AB  - Leg ulcers are a common health problem. Ulcers of any etiology including venous
      ulcers may be very painful, but until recently, health professionals have not
      been good at recognizing or managing this type of pain. It is important to
      clarify the type, severity, and frequency of pain and to anticipate pain at
      dressing changes. The measurement of pain by the use of pain scales is very
      useful, particularly in assessing the efficacy of an intervention. Neuropathic
      pain and unusually painful ulcerations are discussed in this article.

PMID- 15866848
TI  - The management of lower extremity wounds using topical negative pressure.
AB  - The delivery of topical pressures at subatmospheric levels to heal acute and
      chronic wounds has been widely reported. This article reviews the role of this
      therapeutic modality to treat wounds of the lower extremity. Recent literature is
      re-viewed, and mechanisms of action of this process are also discussed.

PMID- 15866849
TI  - Leg ulcers of unusual causes.
AB  - In this review, unusual causes of leg ulcers are examined with an emphasis on
      pathophysiology, clinical presentation, and epidemiology. Cutaneous ulcers due to
      malignancy of unusual leg ulcers with hematologic disorders, vasculitis,
      sarcoidosis, calciphylaxis, Buerger's disease, and pyoderma gangrenosum are
      discussed.

PMID- 15866850
TI  - Imaging the ankle and foot and using magnetic resonance imaging.
AB  - Magnetic resonance (MR) imaging has improved the possibility of evaluating
      musculoskeletal structures thus gaining an important role in the diagnosis and
      treatment of foot and ankle pathologies. In this review, the normal and
      pathological images of the ankle and foot obtained using MR techniques are
      presented and discussed. The high soft-tissue contrast resolution and the
      multiplanar sections of MRI allow the imaging of contiguous tissues where small
      contrast differences exist, such as ligamentous and tendinous injuries or
      impingement syndromes. The spatial resolution with high sensitivity for bone
      signal changes offers an early detection of osseous abnormalities such as stress
      fractures or osteonecrosis. Here it is specified possibilities and limitations of
      MRI in the diabetic foot: this technique is superior to nuclear medicine and
      computed tomography (CT), however it is unable to distinguish between neuro
      arthropathy and infection.

PMID- 15866851
TI  - Microdialysis--a model for studying chronic wounds.
AB  - Microdialysis has been used for more than 20 years as a method of sampling the
      interstitial fluid space. It has been used in both animals and human tissues, in
      vivo. The principle of microdialysis is based on the passive diffusion of a
      compound along its concentration gradient. One major advantage of this sampling
      technique is that it is simple, relatively cheap, and minimally invasive.
      Consequently, microdialysis has been employed in a variety of research and
      clinical settings to recover endogenous molecules and metabolites from the tissue
      space. It has also been used to measure the tissue penetration of xenobiotics and
      to follow their temporal and spatial distribution. Most recently, microdialysis
      has begun to be used as a diagnostic tool and its application to clinical
      investigation at the bedside explored. This review describes the principles of
      the technique of microdialysis and its current uses in both an experimental and
      clinical setting. It goes on to consider current methods of wound fluid sampling
      and the range of bioactive molecules that have been detected in wound fluid
      recovered using these techniques. Finally, the use of microdialysis as a novel
      method for sampling wound fluid in vivo and its ability to provide a fluid that
      is unaffected by the sampling method and that is representative of the wound
      environment is discussed.

PMID- 15866852
TI  - Acute compartment syndrome of the lower leg: changing concepts.
AB  - The acute limb compartment syndrome is caused by bleeding or edema in a closed
      muscle compartment surrounded by fascia and bone, leading to muscle and nerve
      ischemia. The value of fasciotomy has been demonstrated in the management of
      acute compartment syndrome, but if performed after a delay of 8 to 10 hours, it
      can prove to be a double-edged weapon, as necrotic muscle would get exposed
      leading to muscle infections and massive bleeding.

PMID- 15866853
TI  - Ulcerated necrobiosis lipoidica: a combined treatment approach with
      dermatosurgery and PUVA.
AB  - Ulcerated necrobiosis lipoidica is one of the differential diagnoses in leg
      ulcers. The diagnosis is confirmed by histopathology. The authors report on a 68
      year-old female patient with a history of chronic venous insufficiency who
      developed a chronic leg ulcer that did not respond to good ulcer care and
      compression bandaging. Skin biopsies revealed necrobiosis lipoidica. The patient
      was recently discovered to have diabetes mellitus that was treated orally by
      ascarose. Phlebosurgery and mesh grafting were performed, and the patient was
      given pentoxyfiline, dapsone, and clofazimine, but none of these treatments was
      successful. Therefore, topical PUVA therapy was introduced that resulted in
      partial remission and stabilizing of the residual pathology. Based on these
      experiences, the use of surgical methods alone is questionable.

PMID- 15866854
TI  - Children's sleep: an interplay between culture and biology.
AB  - Pediatricians provide a major source of knowledge for parents about children's
      behavior and development, although their advice is largely based on their own
      cultural values and beliefs in interaction with their personal and clinical
      experience. This review presents cross-cultural aspects of children's sleep
      behavior in industrialized and complex modern societies and provides a basis for
      understanding dimensions and mechanisms of cultural differences. We submit that
      it is the interaction between culture and biology that establishes behavioral and
      developmental norms and expectations regarding normal and problematic children's
      sleep. Pediatricians need to recognize the cultural environment in which children
      live and be knowledgeable about how cultural beliefs and values of both families
      and physicians interact with the needs and biological characteristics of
      individual children.

PMID- 15866855
TI  - Sleep-related nighttime crying (yonaki) in Japan: a community-based study.
AB  - OBJECTIVE: To examine factors associated with the phenomenon of yonaki, or sleep
      related nighttime crying (SRNC), in Japanese children METHODS: A cross-sectional
      design incorporating parental self-report was used to investigate relationships
      between developmental, psychologic, and constitutional/physiological factors in
      the incidence of SRNC. Participants were the parents of 170 infants, 174
      toddlers, and 137 children at a well-infant clinic in Tokyo, Japan. RESULTS: The
      lifetime incidence rates of SRNC were 18.8% (infants), 64.9% (toddlers), and
      59.9% (children). At all ages, children were most likely to cosleep with their
      parents; however, infants with reported SRNC were found to cosleep more
      frequently, whereas infants without SRNC were more likely to sleep in separate,
      child-dedicated beds. Toddlers with frequent SRNC were more likely to have
      irregular bedtimes and to have nonparental day care than were those without SRNC.
      Preschoolers who typically slept 9.5 to 10.5 hours per night were less likely to
      report SRNC than were children with longer or shorter nighttime sleep durations.
      In all groups, children with frequent SRNC were more likely to suffer from
      chronic eczema, and toddlers and preschoolers with SRNC exhibited bruxism more
      frequently. CONCLUSIONS: The traditional Japanese arrangement of cosleeping
      represents an environment in which parents are readily accessible to children
      during waking episodes. Physical proximity to the parents in infancy, but not at
      other ages, is associated with SRNC. The higher incidence of bruxism, chronic
      eczema, and day care use among children with frequent SRNC supports the
      hypothesis that nighttime anxiety may promote SRNC.

PMID- 15866856
TI  - Racial differences in reported napping and nocturnal sleep in 2- to 8-year-old
      children.
AB  - OBJECTIVES: The objectives of this study were to examine racial differences in
      reported napping and nighttime sleep of 2- to 8-year-old children, to identify
      factors accounting for these differences, and to determine if variability in
      napping was related to psychosocial functioning. METHODS: Caretakers of 1043
      children (73.5% non-Hispanic white; 50.4% male) 2 to 8 years old from a community
      sample reported on their children's napping behavior and nighttime sleep.
      Caretakers of 255 preschool children (3-5 years old) also completed the Behavior
      Assessment System for Children. RESULTS: A more gradual age-related decline in
      napping was found for black children. At age 8, 39.1% of black children were
      reported to nap, compared with only 4.9% of white children. Black children also
      napped significantly more days per week, had shorter average nocturnal sleep
      durations, and slept significantly less on weekdays than on weekend nights.
      Despite differences in sleep distribution, total weekly sleep duration (diurnal
      and nocturnal) was nearly identical for the 2 racial groups at each year of age.
      Logistic regression analysis revealed that demographic variables were related to
      but did not fully explain napping differences. Napping in a subset of
      preschoolers was not significantly related to psychosocial functioning.
      CONCLUSIONS: There are remarkable racial differences in reported napping and
      nighttime sleep patterns beginning as early as age 3 and extending to at least 8
      years of age. These differences are independent of commonly investigated
      demographic factors. Differences in napping behavior do not seem to have
      psychosocial significance in a sample of preschool children.

PMID- 15866857
TI  - A longitudinal study of bed sharing and sleep problems among Swiss children in
      the first 10 years of life.
AB  - OBJECTIVE: To study age trends, long-term course and secular changes of bed
      sharing practices, and sleep problems among Swiss families. METHODS: A total of
      493 children were longitudinally followed between 1974 and 2001 by using
      structured sleep-related interviews at 1, 3, 6, 9, 12, 18, and 24 months after
      birth and at annual intervals thereafter until 10 years of age. Parents were
      queried about bed sharing, night wakings, bedtime resistance, and sleep-onset
      difficulties during the 3 months before each follow-up interview. RESULTS:
      Although in the first year of life relatively few children slept with their
      parents (<10%), bed sharing increased with age and reached a maximum at 4 years
      (> or =1 times per week: 38%). Bed sharing of at least once per week was noted in
      44% of the children between 2 and 7 years old. Nocturnal wakings also increased
      from 6 months old to a maximum at 4 years, when more than half of all children
      woke up at least once per week (22% every night at 3 years). Less than 10% of all
      children demonstrated frequent bedtime resistance and sleep-onset difficulties.
      Bed sharing and night wakings during early infancy were not predictive for bed
      sharing or night wakings during childhood, whereas both bed sharing and night
      wakings during childhood tended to persist over time. In contrast, bedtime
      resistance and sleep-onset difficulties seemed to be rather transient phenomena
      across all ages. No consistent cohort trends were found except for bedtime
      resistance, which decreased significantly between 1974 and 2001. CONCLUSIONS: Bed
      sharing and nocturnal wakings are common during early childhood. Developmental
      changes in separation-attachment processes, cognitive capabilities to develop
      self-recognition and nighttime fears, and motor locomotion may contribute to the
      particular age trend of night wakings and bed sharing during early childhood.

PMID- 15866858
TI  - Sleep patterns and sleep problems among schoolchildren in the United States and
      China.
AB  - OBJECTIVES: Sleep patterns and sleep problems in children are not only influenced
      by a large number of biological and psychologic factors but also by cultural and
      social factors. Little is known about similarities and differences in sleep
      patterns and sleep problems among children across countries. We attempted to
      compare sleep patterns and sleep problems among schoolchildren from 2 countries
      with distinctive cultural contexts: the United States and China. METHODS: The
      data come from 2 cross-sectional surveys in 3 elementary schools of Jinan City,
      People's Republic of China, and 3 elementary schools from a suburban school
      district in southeastern New England, United States. The Chinese sample consisted
      of 517 elementary school children (grades 1 to 5), and the US sample consisted of
      494 elementary school children (grades kindergarten through 4). We used the
      Children's Sleep Habits Questionnaire (CSHQ) to assess children's sleep patterns
      and sleep problems as reported by parents. Parents of the Chinese sample
      completed a Chinese version of the CSHQ. RESULTS: For children in both the US and
      Chinese samples, reported bedtime was delayed and sleep duration decreased with
      increasing age. Compared with the US children (grades 1-4), Chinese children went
      to bed approximately half an hour later (9:02 vs 8:27 pm) and woke up half an
      hour earlier (6:28 vs 6:55 am), resulting in an average sleep duration that was 1
      hour less (9.25 vs 10.15 hours). Chinese children were rated significantly higher
      than the US children on almost all CSHQ scales, indicating more sleep problems in
      Chinese children. Common sleep problems observed for all children were difficulty
      falling asleep, having a fear of sleeping in the dark, sleep talking, restless
      sleep, teeth grinding during sleep, and daytime sleepiness. Shorter daily sleep
      duration was associated with difficulty falling asleep, struggling at bedtime,
      and trouble sleeping away for the US children, and with going to bed at different
      times and having a fear of sleeping alone for Chinese children. Short sleep
      duration was a main predictor of daytime sleepiness for Chinese children, whereas
      restless sleep and snoring predicted daytime sleepiness for the US children.
      CONCLUSIONS: As reported by parents, children in China went to bed later and woke
      up earlier and their sleep duration was 1 hour shorter than the US children.
      Chinese children were reported to have more sleep problems than their US
      counterparts. Daytime sleepiness was determined by sleep duration only for those
      who slept insufficiently. Unique school schedules and sleep practices may
      contribute to the differences in the sleep patterns and sleep problems of
      children from the United States and China.

PMID- 15866859
TI  - Age-related changes in sleep/wake patterns among Korean teenagers.
AB  - INTRODUCTION: As children go through the transition from childhood to
      adolescence, many shifts occur in sleep/wake patterns related to intrinsic and
      extrinsic developmental changes. These shifts have been shown to result in
      corresponding shifts in sleep phase (later sleep onset) and sleep deprivation
      among teenagers in Western societies. However, the effect of these developmental
      changes on the sleep habits of Korean teenagers has not been analyzed. This study
      aims to quantify age-related changes in sleep/wake patterns among Korean
      teenagers and elucidate cultural and other factors causing these changes.
      METHODS: The School Sleep Habits Survey was administered in homeroom classes to
      students in grades 5 to 12 (mean age: 13.7 +/- 2.4 years) selected via a 2-way
      stratification sampling method. The survey included items regarding usual
      sleep/wake patterns over the previous 2 weeks as well as measures of daytime
      sleepiness, sleep/wake-problem behavior, depressed mood, and
      morningness/eveningness. RESULTS: A total of 1457 students (52.9% male) completed
      the survey. The higher the grade, the later bedtime was found to be on both
      school days and weekends. There was a similar relationship between increasing
      grade and earlier wake time on school days, but higher grades were associated
      with later wake time on weekends. Total sleep time decreased by approximately 3
      hours on school nights and 1 hour on weekend nights from grades 5 to 12.
      Adolescents were severely sleep deprived, with mean school-night total sleep
      times of 6.02, 5.62, and 4.86 hours for 10th-, 11th-, and 12th-graders,
      respectively. In the higher grades, there was a greater discrepancy between
      school nights and weekends in terms of bedtime and wake time, and the magnitude
      of weekend oversleep increased. Older students also reported more daytime
      sleepiness, more sleep/wake-problem behavior, more depressed mood, and more
      eveningness preference. The chief reasons students cited for their sleep
      deprivation differed across grades: Academic demands and entertainment (such as
      Internet and television) were reported by 5th- and 6th-graders, entertainment and
      then academic demands by 7th-, 8th-, and 9th-graders, and early school start time
      and academic demands by 10th-, 11th- and 12th-graders. CONCLUSIONS: This study
      clearly demonstrates that Korean adolescents do not get adequate sleep and that
      they have profound discrepancies in their sleep/wake patterns between school and
      weekend nights. Compared with previous studies from other countries, Korean
      students display even greater sleep deprivation and also more irregular
      sleep/wake patterns. This study also demonstrates that academic demands/stress
      and early school start time are the most important contributing factors for sleep
      deprivation among Korean adolescents. These findings stress the need to promote
      awareness of the magnitude of adolescent sleep deprivation and its detrimental
      effects in Korean society.

PMID- 15866860
TI  - The relationship between reported sleep quality and sleep hygiene in Italian and
      American adolescents.
AB  - OBJECTIVE: The purpose of the study was to examine the relationship between self
      reported sleep quality and sleep hygiene in Italian and American adolescents and
      to assess whether sleep-hygiene practices mediate the relationship between
      culture and sleep quality. METHODS: Two nonprobability samples were collected
      from public schools in Rome, Italy, and Hattiesburg, Mississippi. Students
      completed the following self-report measures: Adolescent Sleep-Wake Scale,
      Adolescent Sleep Hygiene Scale, Pubertal Developmental Scale, and
      Morningness/Eveningness Scale. RESULTS: The final sample included 776 Italian and
      572 American adolescents 12 to 17 years old. Italian adolescents reported much
      better sleep hygiene and substantially better sleep quality than American
      adolescents. A moderate-to-strong linear relationship was found between sleep
      hygiene and sleep quality in both samples. Separate hierarchical multiple
      regression analyses were performed on both samples. Demographic and individual
      characteristics explained a significant proportion of the variance in sleep
      quality (Italians: 18%; Americans: 25%), and the addition of sleep-hygiene
      domains explained significantly more variance in sleep quality (Italians: 17%;
      Americans: 16%). A final hierarchical multiple regression analysis with both
      samples combined showed that culture (Italy versus United States) only explained
      0.8% of the variance in sleep quality after controlling for sleep hygiene and all
      other variables. CONCLUSIONS: Cross-cultural differences in sleep quality, for
      the most part, were due to differences in sleep-hygiene practices. Sleep hygiene
      is an important predictor of sleep quality in Italian and American adolescents,
      thus supporting the implementation and evaluation of educational programs on good
      sleep-hygiene practices.

PMID- 15866861
TI  - Brief report: An epidemiologic survey of the prevalence of sleep disorders among
      children 2 to 12 years old in Beijing, China.
AB  - OBJECTIVE: This survey was conducted to examine the prevalence of sleep disorders
      in 2- to 12-year-old children in the Beijing area of China. METHODS: From October
      2001 to June 2002, 5979 children 2 to 12 years old in 6 randomly selected
      counties in Beijing were investigated with questionnaires. RESULTS: The average
      total sleep time per day ranged from 11.38 hours among 2-year-olds down to 9.34
      hours among 12-year-olds. The overall prevalence of sleep disorders was 21.2% and
      included parasomnia symptoms (bruxism [6.5%], sleep talking [4.9%], enuresis
      [1.0%], sleepwalking [0.6%], restless sleep [5.0%], and leg movements [1.9%]) and
      symptoms of sleep-disordered breathing (frequent snoring [5.6%], mouth breathing
      [4.1%], choking/gasping [0.9%], and breathing pauses [0.2%]). CONCLUSION: The
      overall prevalence of parent-reported symptoms of sleep disorders in a large
      sample of children in Beijing, China, was comparable to that reported in other
      countries, although the prevalence of some specific symptoms differed somewhat.

PMID- 15866862
TI  - Commentary: Sleep in German infants--the "cult" of independence.
AB  - OBJECTIVES: Significant cultural variations exist in sleep practices for young
      children, including bedtime rituals and routines, soothing techniques, and
      cosleeping. This study examined parenting styles at bedtime and sleep behavior in
      a group of German infants. The results are compared with sleep practices of other
      western European countries. PARTICIPANTS: German parents of 50 boys and 50 girls
      6 to 30 months old. METHOD: Parents were asked to fill out a questionnaire about
      the sleep behavior of their child. Personal interviews with the parents were
      conducted to augment the survey results; in selected cases, bedtime routines were
      filmed. RESULTS: The infants in this sample largely slept in their own bed in a
      separate room. Bedtime rituals were common and in general characterized by
      parents maintaining behavioral distance from the infants during the bedtime
      routine. However, parenting style was likely to become more "proximal" (close) in
      response to bedtime refusal and nocturnal infant crying. A majority of parents
      (79%) used lullabies as part of the bedtime ritual, and the use of a sleep aid
      was very common (80%). CONCLUSION: As is the case with most cultures, German
      bedtime parenting practices tend to reflect parenting values and beliefs
      associated with their specific culture. The parenting style at bedtime in this
      group of infants in general seemed less rigid and less distancing than bedtime
      rituals typically described in other northern European countries and may
      represent more of a synthesis of parenting styles across various Western
      cultures.

PMID- 15866863
TI  - Community-based interventions for improving perinatal and neonatal health
      outcomes in developing countries: a review of the evidence.
AB  - BACKGROUND: Infant and under-5 childhood mortality rates in developing countries
      have declined significantly in the past 2 to 3 decades. However, 2 critical
      indicators, maternal and newborn mortality, have hardly changed. World leaders at
      the United Nations Millennium Summit in September 2000 agreed on a critical goal
      to reduce deaths of children <5 years by two thirds, but this may be unattainable
      without halving newborn deaths, which now comprise 40% of all under-5 deaths.
      Greater emphasis on wide-scale implementation of proven, cost-effective measures
      is required to save women's and newborns' lives. Approximately 99% of neonatal
      deaths take place in developing countries, mostly in homes and communities. A
      comprehensive review of the evidence base for impact of interventions on neonatal
      health and survival in developing-country communities has not been reported.
      OBJECTIVE: This review of community-based antenatal, intrapartum, and postnatal
      intervention trials in developing countries aimed to identify (1) key behaviors
      and interventions for which the weight of evidence is sufficient to recommend
      their inclusion in community-based neonatal care programs and (2) key gaps in
      knowledge and priority areas for future research and program learning. METHODS:
      Available published and unpublished data on the impact of community-based
      strategies and interventions on perinatal and neonatal health status outcomes
      were reviewed. Evidence was summarized systematically and categorized into 4
      levels of evidence based on study size, location, design, and reported impact,
      particularly on perinatal or neonatal mortality. The evidence was placed in the
      context of biological plausibility of the intervention; evidence from relevant
      developed-country studies; health care program experience in implementation; and
      recommendations from the World Health Organization and other leading agencies.
      RESULTS: A paucity of community-based data was found from developing-country
      studies on health status impact for many interventions currently being considered
      for inclusion in neonatal health programs. However, review of the evidence and
      consideration of the broader context of knowledge, experience, and
      recommendations regarding these interventions enabled us to categorize them
      according to the strength of the evidence base and confidence regarding their
      inclusion now in programs. This article identifies a package of priority
      interventions to include in programs and formulates research priorities for
      advancing the state of the art in neonatal health care. CONCLUSIONS: This review
      emphasizes some new findings while recommending an integrated approach to safe
      motherhood and newborn health. The results of this study provide a foundation for
      policies and programs related to maternal and newborn health and emphasizes the
      importance of health systems research and evaluation of interventions. The review
      offers compelling support for using research to identify the most effective
      measures to save newborn lives. It also may facilitate dialogue with policy
      makers about the importance of investing in neonatal health.

PMID- 15866864
TI  - Is the water rising?

PMID- 15866865
TI  - Cross-talk between fMLP and vitronectin receptors triggered by urokinase receptor
      derived SRSRY peptide.
AB  - The urokinase-type plasminogen activator receptor (uPAR) sustains cell migration
      through its capacity to promote pericellular proteolysis, regulate integrin
      function, and mediate chemotactic signaling in response to urokinase. We have
      characterized the early signaling events triggered by the Ser-Arg-Ser-Arg-Tyr
      (SRSRY) chemotactic uPAR sequence. Cell exposure to SRSRY peptide promotes
      directional migration on vitronectin-coated filters, regardless of uPAR
      expression, in a specific and dose-dependent manner, with maximal effect at a
      concentration level as low as 10 nm. A similar concentration profile is observed
      in a quantitative analysis of SRSRY-dependent cytoskeletal rearrangements, mostly
      consisting of filamentous structures localized in a single cell region. SRSRY
      analogues with alanine substitutions fail to drive F-actin formation and cell
      migration, indicating a critical role for each amino acid residue. As with ligand
      dependent uPAR signaling, SRSRY stimulates protein kinase C activity and results
      in ERK1/2 phosphorylation. The involvement of the high affinity N-formyl-Met-Leu
      Phe receptor (FPR) in this process is indicated by the finding that 100 nm N
      formyl-Met-Leu-Phe inhibits binding of D2D3 to the cell surface, as well as SRSRY
      stimulated cell migration and F-actin polarization. Moreover, cell exposure to
      SRSRY promotes FPR-dependent vitronectin release and increased uPAR.alphavbeta5
      vitronectin receptor physical association, indicating that alphavbeta5 activity
      is regulated by the SRSRY uPAR sequence via FPR. Finally, we provide evidence
      that alphavbeta5 is required for SRSRY-dependent ERK1/2 phosphorylation, whereas
      it is not required for protein kinase C activation. The data indicate that the
      ability of uPAR to stimulate cell migration and cytoskeletal rearrangements is
      retained by the SRSRY peptide alone and that it is supported by cross-talk
      between FPR and alphavbeta5.

PMID- 15866866
TI  - Structural determinants of factor IX(a) binding in nitrophorin 2, a lipocalin
      inhibitor of the intrinsic coagulation pathway.
AB  - Nitrophorin 2 (NP2) is a salivary lipocalin from Rhodnius prolixus that binds
      with coagulation factors IX (fIX) and IXa (fIXa). Binding of NP2 with fIXa
      results in potent inhibition of the intrinsic factor Xase complex. A panel of
      site-directed surface mutants of NP2 was generated to locate determinants of high
      affinity fIX(a) binding. The locations of the mutations were based on comparisons
      with the related, but less potent, inhibitor nitrophorin 3 (NP3). Three point
      mutants (K21A, K92A, and V94A) were found that clearly reduced the inhibitory
      potency as measured by the activity of a reconstituted factor Xase system.
      Binding of NP2 with fIXa and fIX as measured by surface plasmon resonance and
      isothermal titration calorimetry was reduced in a similar manner. Of the three
      mutants, two (K92A and V94A) were located on the loop connecting beta-strands E
      and F of the lipocalin beta-barrel. The largest changes were seen with the K92A
      mutation, which lies at the apex of the loop, with a smaller effect being seen
      with mutation of Val(94). Combination of four E-F loop mutations (K92A, A93K,
      V94A, E97A) in a single mutant reduced the inhibitory potency and binding to
      levels similar to those seen with NP3 without affecting heme or histamine
      binding.

PMID- 15866867
TI  - A multifunctional domain of the calcium-responsive transactivator (CREST) that
      inhibits dendritic growth in cultured neurons.
AB  - The calcium-responsive transactivator (CREST) is targeted to nuclear bodies and
      is required for the normal development of neuronal dendritic trees. Here we
      report the identification of a multifunctional domain (MFD) of CREST that is
      involved in transcription transactivation, nuclear body targeting, and
      dimerization. MFD is located near the C terminus of CREST from amino acid 251 to
      322 and is required and sufficient for CREST homodimerization. When fused with a
      GAL4 DNA-binding domain, MFD was effective in transcription transactivation of a
      luciferase reporter system. A C-terminal 339-401 amino acid sequence of CREST was
      shown to contain a nuclear localization signal (NLS), which was able to direct a
      yellow fluorescence protein (YFP) to nucleus. A CREST deletion mutant containing
      both the MFD and NLS, which spanned the C-terminal amino acid sequence 251-401,
      was able to target YFP to the nucleus and nuclear bodies. However, MFD alone
      failed to target YFP and was largely cytosolic. The addition of a SV40 NLS to MFD
      domain restored nuclear body targeting. When YFP-MFD was expressed in cultured
      rat embryonic cortical neurons, it was effective in inhibiting depolarization
      induced dendritic growth, suggesting that CREST dimerization may be necessary for
      its function in neuronal dendritic development.

PMID- 15866868
TI  - Two residues of rubisco activase involved in recognition of the Rubisco
      substrate.
AB  - Rubisco activase is an AAA(+) protein, a superfamily with members that use a
      "Sensor 2" domain for substrate recognition. To determine whether the analogous
      domain of activase is involved in recognition of ribulose-1,5-bisphosphate
      carboxylase/oxygenase (Rubisco, EC 4.1.1.39), two chimeric activases were
      constructed, interchanging a Sensor 2-containing region between activases from
      spinach and tobacco. Spinach chimeric activase was a poor activator of both
      spinach and tobacco Rubisco. In contrast, tobacco chimeric activase activated
      spinach Rubisco far better than tobacco Rubisco, similar to spinach activase. A
      point mutation, K311D, in the Sensor 2 domain of the tobacco chimeric activase
      abolished its ability to better activate spinach Rubisco. The opposite mutation,
      D311K, in wild type tobacco activase produced an enzyme that activated both
      spinach and tobacco Rubisco, whereas a second mutation, D311K/L314V, shifted the
      activation preference toward spinach Rubisco. The involvement of these two
      residues in substrate selectivity was confirmed by introducing the analogous
      single and double mutations in cotton activase. The ability of the two tobacco
      activase mutants to activate wild type and mutant Chlamydomonas Rubiscos was also
      examined. Tobacco D311K activase readily activated wild type and P89R but not
      D94K Rubisco, whereas the tobacco L314V activase only activated D94K Rubisco. The
      tobacco activase double mutant D311K/L314V activated wild type Chlamydomonas
      Rubisco better than either the P89R or D94K Rubisco mutants, mimicking activation
      by spinach activase. The results identified a substrate recognition region in
      activase in which two residues may directly interact with two residues in
      Rubisco.

PMID- 15866869
TI  - Isolation of sterol-resistant Chinese hamster ovary cells with genetic
      deficiencies in both Insig-1 and Insig-2.
AB  - Insig-1 and Insig-2, a pair of endoplasmic reticulum (ER) membrane proteins,
      mediate feedback control of cholesterol synthesis through their sterol-dependent
      binding to the following two polytopic ER membrane proteins: sterol regulatory
      element-binding protein (SREBP) cleavage-activating protein (SCAP) and 3-hydroxy
      3-methylglutaryl-coenzyme A reductase. Sterol-induced binding of Insigs to SCAP
      prevents the proteolytic processing of SREBPs, membrane-bound transcription
      factors that enhance the synthesis of cholesterol, by retaining complexes between
      SCAP and SREBP in the ER. Sterol-induced binding of Insigs to reductase leads to
      the ubiquitination and ER-associated degradation of the enzyme, thereby slowing a
      rate-controlling step in cholesterol synthesis. Here we report the isolation of a
      new line of mutant Chinese hamster ovary cells, designated SRD-15, deficient in
      both Insig-1 and Insig-2. The SRD-15 cells were produced by gamma-irradiation of
      Insig-1-deficient SRD-14 cells, followed by selection in high levels of the
      oxysterol, 25-hydroxycholesterol. Sterols neither inhibit SREBP processing nor
      promote reductase ubiquitination/degradation in SRD-15 cells. Sterol regulation
      of SREBP processing and reductase ubiquitination/degradation is fully restored in
      SRD-15 cells when they are transfected with expression plasmids encoding either
      Insig-1 or Insig-2. These results demonstrate an absolute requirement for Insig
      proteins in the regulatory system that mediates lipid homeostasis in animal
      cells.

PMID- 15866870
TI  - Functional characterization of the iron-regulatory transcription factor Fep1 from
      Schizosaccharomyces pombe.
AB  - In response to excess iron, Schizosaccharomyces pombe cells repress transcription
      of genes encoding components involved in iron uptake through the Fep1
      transcription factor. Fep1 mediates this control by interacting with the
      consensus sequence 5'-(A/T)GATAA-3', found in iron-dependent promoters. In this
      report, we show that Fep1 localizes to the nucleus under both iron-replete and
      iron-starved conditions. The Fep1 DNA binding domain (amino acids 1-241) contains
      two GATA-type zinc finger motifs. Although we determine that the Fep1 C-terminal
      zinc finger (ZF2) is essential for DNA binding, we show that the N-terminal zinc
      finger (ZF1) enhances DNA binding affinity approximately 5-fold. Between the two
      zinc finger motifs of Fep1 resides an invariant amino acid sequence, denoted the
      Cys-rich region (amino acids 68-94), in which four highly conserved Cys residues
      are found. Cells harboring mutant alleles in which two or more of the conserved
      Cys residues were substituted by alanine exhibited elevated fio1(+) mRNA levels.
      We determine that the dissociation constant for the resulting complex between
      each of the Cys mutants and the sequence 5'-(A/T)GATAA-3' reflects a much lower
      affinity that correlates with failure to repress fio1(+) gene expression.
      Deletion analysis identified two heptad repeats (amino acids 522-536) within the
      C-terminal region of Fep1 that are necessary and sufficient to mediate Fep1
      dimerization. Moreover, mutations that impair dimerization also negatively affect
      transcriptional repression. Together these findings reveal several novel features
      of Fep1, a non-canonical GATA factor required for iron homeostasis.

PMID- 15866871
TI  - The role of protein-tyrosine phosphatase 1B in integrin signaling.
AB  - Protein-tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin
      and leptin signaling and a novel therapeutic target for the treatment of type 2
      diabetes, obesity, and other associated metabolic syndromes. Because PTP1B
      regulates multiple signal pathways and it can both enhance and antagonize a
      cellular event, it is important to establish the physiological relevance of PTP1B
      in these processes. In this study, we utilize potent and selective PTP1B
      inhibitors to delineate the role of PTP1B in integrin signaling. We show that
      down-regulation of PTP1B activity with small molecule inhibitors suppresses cell
      spreading and migration to fibronectin, increases Tyr(527) phosphorylation in
      Src, and decreases phosphorylation of FAK, p130(Cas), and ERK1/2. In addition,
      PTP1B "substrate-trapping" mutants bind Tyr(527)-phosphorylated Src and protect
      it from dephosphorylation by endogenous PTP1B. These results establish that PTP1B
      promotes integrin-mediated responses in fibroblasts by dephosphorylating the
      inhibitory pTyr(527) and thereby activating the Src kinase. We also show that
      PTP1B forms a complex with Src and p130(Cas), and that the proline-rich motif
      PPRPPK (residues 309-314) in PTP1B is essential for the complex formation. We
      suggest that the specificity of PTP1B for Src pTyr(527) is mediated by protein
      protein interactions involving the docking protein p130(Cas) with both Src and
      PTP1B in addition to the interactions between the PTP1B active site and the
      pTyr(527) motif.

PMID- 15866872
TI  - Elucidation of gene-to-gene and metabolite-to-gene networks in arabidopsis by
      integration of metabolomics and transcriptomics.
AB  - Since the completion of genome sequences of model organisms, functional
      identification of unknown genes has become a principal challenge in biology. Post
      genomics sciences such as transcriptomics, proteomics, and metabolomics are
      expected to discover gene functions. This report outlines the elucidation of gene
      to-gene and metabolite-to-gene networks via integration of metabolomics with
      transcriptomics and presents a strategy for the identification of novel gene
      functions. Metabolomics and transcriptomics data of Arabidopsis grown under
      sulfur deficiency were combined and analyzed by batch-learning self-organizing
      mapping. A group of metabolites/genes regulated by the same mechanism clustered
      together. The metabolism of glucosinolates was shown to be coordinately
      regulated. Three uncharacterized putative sulfotransferase genes clustering
      together with known glucosinolate biosynthesis genes were candidates for
      involvement in biosynthesis. In vitro enzymatic assays of the recombinant gene
      products confirmed their functions as desulfoglucosinolate sulfotransferases.
      Several genes involved in sulfur assimilation clustered with O-acetylserine,
      which is considered a positive regulator of these genes. The genes involved in
      anthocyanin biosynthesis clustered with the gene encoding a transcriptional
      factor that up-regulates specifically anthocyanin biosynthesis genes. These
      results suggested that regulatory metabolites and transcriptional factor genes
      can be identified by this approach, based on the assumption that they cluster
      with the downstream genes they regulate. This strategy is applicable not only to
      plant but also to other organisms for functional elucidation of unknown genes.

PMID- 15866873
TI  - A two-component hydroxylase involved in the assimilation of 3-hydroxyphenyl
      acetate in Pseudomonas putida.
AB  - The complete catabolic pathway involved in the assimilation of 3
      hydroxyphenylacetic acid (3-OH-PhAc) in Pseudomonas putida U has been
      established. This pathway is integrated by the following: (i) a specific route
      (upper pathway), which catalyzes the conversion of 3-OH-PhAc into 2,5
      dihydroxyphenylacetic acid (2,5-diOH-PhAc) (homogentisic acid, Hmg), and (ii) a
      central route (convergent route), which catalyzes the transformation of the Hmg
      generated from 3-OH-PhAc, l-Phe, and l-Tyr into fumarate and acetoacetate
      (HmgABC). Thus, in a first step the degradation of 3-OH-PhAc requires the uptake
      of 3-OH-PhAc by means of an active transport system that involves the
      participation of a permease (MhaC) together with phosphoenolpyruvate as the
      energy source. Once incorporated, 3-OH-PhAc is hydroxylated to 2,5-diOH-PhAc
      through an enzymatic reaction catalyzed by a novel two-component flavoprotein
      aromatic hydroxylase (MhaAB). The large component (MhaA, 62,719 Da) is a
      flavoprotein, and the small component (MhaB, 6,348 Da) is a coupling protein that
      is essential for the hydroxylation of 3-OH-PhAc to 2,5-diOH-PhAc. Sequence
      analyses and molecular biology studies revealed that homogentisic acid synthase
      (MhaAB) is different from the aromatic hydroxylases reported to date, accounting
      for its specific involvement in the catabolism of 3-OH-PhAc. Additionally, an ABC
      transport system (HmgDEFGHI) involved in the uptake of homogentisic acid and two
      regulatory elements (mhaSR and hmgR) have been identified. Furthermore, the
      cloning and the expression of some of the catabolic genes in different microbes
      presented them with the ability to synthesize Hmg (mhaAB) or allowed them to grow
      in chemically defined media containing 3-OH-PhAc as the sole carbon source (mhaAB
      and hmgABC).

PMID- 15866874
TI  - Pex5p, the peroxisomal cycling receptor, is a monomeric non-globular protein.
AB  - In mammals, targeting of newly synthesized peroxisomal matrix proteins to the
      organelle requires Pex5p, the peroxisomal cycling receptor. Pex5p is a
      multidomain protein involved in a complex network of transient protein-protein
      interactions. Besides interacting directly with most peroxisomal proteins en
      route to the organelle, Pex5p has also binding domains for several components of
      the peroxisomal docking/translocation machinery. However, our knowledge of how
      binding of a cargo protein to Pex5p influences its properties is still rather
      limited. Here, we describe a protease assay particularly useful for identifying
      and characterizing protein-protein interactions involving human Pex5p. Binding of
      a PTS1-containing peptide/protein to Pex5p as well as the interaction of this
      peroxin with the Src homology domain 3 of Pex13p could be easily demonstrated
      using this assay. To address the possible effects of these Pex5p-interacting
      peptides/proteins on the assumed quaternary structure of Pex5p, we have analyzed
      the hydrodynamic properties of human Pex5p using size exclusion chromatography,
      sucrose gradient centrifugation, and sedimentation equilibrium centrifugation.
      Our results show that Pex5p is a monomeric protein with an abnormal shape. The
      implications of these findings on current models of protein translocation across
      the peroxisomal membrane are discussed.

PMID- 15866875
TI  - Characterization of the final step in the conversion of phytol into phytanic
      acid.
AB  - Phytol is a branched-chain fatty alcohol that is a naturally occurring precursor
      of phytanic acid, a fatty acid involved in the pathogenesis of Refsum disease.
      The conversion of phytol into phytanic acid is generally believed to take place
      via three enzymatic steps that involve 1) oxidation to its aldehyde, 2) further
      oxidation to phytenic acid, and 3) reduction of the double bond at the 2,3
      position, yielding phytanic acid. Our recent investigations of this mechanism
      have elucidated the enzymatic steps leading to phytenic acid production, but the
      final step of the pathway has not been investigated so far. In this study, we
      describe the characterization of phytenic acid reduction in rat liver. NADPH
      dependent conversion of phytenic acid into phytanic acid was detected, although
      at a slow rate. However, it was shown that phytenic acid can be activated to its
      CoA ester and that reduction of phytenoyl-CoA is much more efficient than that of
      phytenic acid. Furthermore, in rat hepatocytes cultured in the presence of
      phytol, phytenoyl-CoA could be detected, showing that it is a bona fide
      intermediate of phytol degradation. Subcellular fractionation experiments
      revealed that phytenoyl-CoA reductase activity is present in peroxisomes and
      mitochondria. With these findings, we have accomplished the full elucidation of
      the mechanism by which phytol is converted into phytanic acid.

PMID- 15866876
TI  - SIGIRR inhibits interleukin-1 receptor- and toll-like receptor 4-mediated
      signaling through different mechanisms.
AB  - The Toll-interleukin-1 receptor (TIR) domain-containing orphan receptor SIGIRR
      (single immunoglobulin interleukin-1 receptor-related protein) acts as a negative
      regulator of interleukin (IL)-1 and lipopolysaccharide (LPS) signaling.
      Endogenous SIGIRR transiently interacted with IL-1 receptor and the receptor
      proximal signaling components (MyD88, IRAK, and tumor necrosis factor receptor
      associated factor 6) upon IL-1 stimulation, indicating that SIGIRR interacts with
      the IL-1 receptor complex in a ligand-dependent manner. Similar interaction was
      also observed between SIGIRR and Toll-like receptor 4 receptor complex upon LPS
      stimulation. To identify the domains of SIGIRR required for its interaction with
      the Toll-like receptor 4 and IL-1 receptor complexes, several SIGIRR deletion
      mutants were generated, including DeltaN (lacking the extracellular
      immunoglobulin (Ig) domain with deletion of amino acids 1-119), DeltaC (lacking
      the C-terminal domain with deletion of amino acids 313-410), and DeltaTIR
      (lacking the TIR domain with deletion of amino acids 161-313). Whereas both the
      extracellular Ig domain and the intracellular TIR domains are important for
      SIGIRR to inhibit IL-1 signaling, only the TIR domain is necessary for SIGIRR to
      inhibit LPS signaling. The extracellular Ig domain exerts its inhibitory role in
      IL-1 signaling by interfering with the heterodimerization of IL-1 receptor and IL
      1RAcP, whereas the intracellular TIR domain inhibits both IL-1 and LPS signaling
      by attenuating the recruitment of receptor-proximal signaling components to the
      receptor. These results indicate that SIGIRR inhibits IL-1 and LPS signaling
      pathways through differential mechanisms.

PMID- 15866877
TI  - An exo-beta-1,3-galactanase having a novel beta-1,3-galactan-binding module from
      Phanerochaete chrysosporium.
AB  - An exo-beta-1,3-galactanase gene from Phanerochaete chrysosporium has been
      cloned, sequenced, and expressed in Pichia pastoris. The complete amino acid
      sequence of the exo-beta-1,3-galactanase indicated that the enzyme consists of an
      N-terminal catalytic module with similarity to glycoside hydrolase family 43 and
      an additional unknown functional domain similar to carbohydrate-binding module
      family 6 (CBM6) in the C-terminal region. The molecular mass of the recombinant
      enzyme was estimated as 55 kDa based on SDS-PAGE. The enzyme showed reactivity
      only toward beta-1,3-linked galactosyl oligosaccharides and polysaccharide as
      substrates but did not hydrolyze beta-1,4-linked galacto-oligosaccharides, beta
      1,6-linked galacto-oligosaccharides, pectic galactan, larch arabinogalactan,
      arabinan, gum arabic, debranched arabinan, laminarin, soluble birchwood xylan, or
      soluble oat spelled xylan. The enzyme also did not hydrolyze beta-1,3-galactosyl
      galactosaminide, beta-1,3-galactosyl glucosaminide, or beta-1,3-galactosyl
      arabinofuranoside, suggesting that it specifically cleaves the internal beta-1,3
      linkage of two galactosyl residues. High performance liquid chromatographic
      analysis of the hydrolysis products showed that the enzyme produced galactose
      from beta-1,3-galactan in an exo-acting manner. However, no activity toward p
      nitrophenyl beta-galactopyranoside was detected. When incubated with
      arabinogalactan proteins, the enzyme produced oligosaccharides together with
      galactose, suggesting that it is able to bypass beta-1,6-linked galactosyl side
      chains. The C-terminal CBM6 did not show any affinity for known substrates of
      CBM6 such as xylan, cellulose, and beta-1,3-glucan, although it bound beta-1,3
      galactan when analyzed by affinity electrophoresis. Frontal affinity
      chromatography for the CBM6 moiety using several kinds of terminal galactose
      containing oligosaccharides as the analytes clearly indicated that the CBM6
      specifically interacted with oligosaccharides containing a beta-1,3-galactobiose
      moiety. When the degree of polymerization of galactose oligomers was increased,
      the binding affinity of the CBM6 showed no marked change.

PMID- 15866878
TI  - Interactions of MotX with MotY and with the PomA/PomB sodium ion channel complex
      of the Vibrio alginolyticus polar flagellum.
AB  - Rotation of the sodium ion-driven polar flagellum of Vibrio alginolyticus
      requires the inner membrane sodium ion channel complex PomA/PomB and the outer
      membrane components MotX and MotY. None of the detergents used in this study were
      able to solubilize MotX when it was expressed alone. However, when co-expressed
      with MotY, MotX was solubilized by some detergents. The change in the solubility
      of MotX suggests that MotY interacts with MotX. In agreement with this, a pull
      down assay showed the association of MotY with MotX. Solubilized MotX and MotY
      eluted in the void volume from a gel-filtration column, suggesting that MotX and
      MotY form a large oligomeric structure(s). In the absence of MotY, MotX affected
      membrane localization of the PomA/PomB complex and of PomB alone but not of PomA
      alone, suggesting an interaction between MotX and PomB. We propose that MotX
      exhibits multiple interactions with the other motor components, first with MotY
      for its localization to the outer membrane and then with the PomA/PomB complex
      through PomB for the motor rotation.

PMID- 15866880
TI  - G Protein activation without subunit dissociation depends on a G{alpha}(i)
      specific region.
AB  - G proteins transmit a variety of extracellular signals into intracellular
      responses. The Galpha and Gbetagamma subunits are both known to regulate
      effectors. Interestingly, the Galpha subunit also determines subtype specificity
      of Gbetagamma effector interactions. However, in light of the common paradigm
      that Galpha and Gbetagamma subunits dissociate during activation, a plausible
      mechanism of how this subtype specificity is generated was lacking. Using a
      fluorescence resonance energy transfer (FRET)-based assay developed to directly
      measure mammalian G protein activation in intact cells, we demonstrate that
      fluorescent Galpha(i1,2,3), Galpha(z), and Gbeta(1)gamma(2) subunits do not
      dissociate during activation but rather undergo subunit rearrangement as
      indicated by an activation-induced increase in FRET. In contrast, fluorescent
      Galpha(o) subunits exhibited an activation-induced decrease in FRET, reflecting
      subunit dissociation or, alternatively, a distinct subunit rearrangement. The
      alpha(B/C)-region within the alpha-helical domain, which is much more conserved
      within Galpha(i1,2,3) and Galpha(z) as compared with that in Galpha(o), was found
      to be required for exhibition of an activation-induced increase in FRET between
      fluorescent Galpha and Gbetagamma subunits. However, the alpha(B/C)-region of
      Galpha(il) alone was not sufficient to transfer the activation pattern of
      Galpha(i) to the Galpha(o) subunit. Either residues in the first 91 amino acids
      or in the C-terminal remainder (amino acids 93-354) of Galpha(il) together with
      the alpha(B/C)-helical region of Galpha(i1) were needed to transform the
      Galpha(o)-activation pattern into a Galpha(i1)-type of activation. The discovery
      of subtype-selective mechanisms of G protein activation illustrates that G
      protein subfamilies have specific mechanisms of activation that may provide a
      previously unknown basis for G protein signaling specificity.

PMID- 15866879
TI  - The ATPase activity of BfpD is greatly enhanced by zinc and allosteric
      interactions with other Bfp proteins.
AB  - Type IV pilus biogenesis, protein secretion, DNA transfer, and filamentous phage
      morphogenesis systems are thought to possess similar architectures and
      mechanisms. These multiprotein complexes include members of the PulE superfamily
      of putative NTPases that have extensive sequence similarity and probably similar
      functions as the energizers of macromolecular transport. We purified the PulE
      homologue BfpD of the enteropathogenic Escherichia coli bundle-forming pilus
      (BFP) biogenesis machine and characterized its ATPase activity, providing new
      insights into its mode of action. Numerous techniques revealed that BfpD forms
      hexamers in the presence of nucleotide. Hexameric BfpD displayed weak ATPase
      activity. We previously demonstrated that the N termini of membrane proteins BfpC
      and BfpE recruit BfpD to the cytoplasmic membrane. Here, we identified two BfpD
      binding sites, BfpE(39-76) and BfpE(77-114), in the N terminus of BfpE using a
      yeast two-hybrid system. Isothermal titration calorimetry and protease
      sensitivity assays showed that hexameric BfpD-ATPgammaS binds to BfpE(77-114),
      whereas hexameric BfpD-ADP binds to BfpE(39-76). Interestingly, the N terminus of
      BfpC and BfpE(77-114) together increased the ATPase activity of hexameric BfpD
      over 1200-fold to a V(max) of 75.3 mumol of P(i) min(-1) mg(-1), which exceeds by
      over 1200-fold the activity of other PulE family members. This augmented activity
      occurred only in the presence of Zn(2+). We conclude that allosteric interactions
      between BfpD and BfpC and BfpE dramatically stimulate its ATPase activity. The
      differential nucleotide-dependent binding of hexameric BfpD to BfpE(39-76) and
      BfpE(77-114) suggests a model for the mechanism by which BfpD transduces
      mechanical energy to the biogenesis machine.

PMID- 15866881
TI  - Plc1p, Arg82p, and Kcs1p, enzymes involved in inositol pyrophosphate synthesis,
      are essential for phosphate regulation and polyphosphate accumulation in
      Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, the phosphate signal transduction PHO pathway is
      involved in regulating several phosphate-responsive genes such as PHO5, which
      encodes repressible acid phosphatase. In this pathway, a cyclin-dependent kinase
      inhibitor (Pho81p) regulates the kinase activity of the cyclin-cyclin-dependent
      kinase complex Pho80p-Pho85p, which phosphorylates the transcription factor Pho4p
      in response to intracellular phosphate levels. However, how cells sense phosphate
      availability and transduce the phosphate signal to Pho81p remains unknown. To
      identify additional components of the PHO pathway, we have screened a collection
      of yeast deletion strains. We found that disruptants of PLC1, ARG82, and KCS1,
      which are involved in the synthesis of inositol polyphosphate, and ADK1, which
      encodes adenylate kinase, constitutively express PHO5. Each of these factors
      functions upstream of Pho81p and negatively regulates the PHO pathway
      independently of intracellular orthophosphate levels. Overexpression of KCS1, but
      not of the other genes, suppressed PHO5 expression in the wild-type strain under
      low phosphate conditions. These results raise the possibility that
      diphosphoinositol tetrakisphosphate and/or bisdiphosphoinositol triphosphate may
      be essential for regulation of the PHO pathway. Furthermore, the Deltaplc1,
      Deltaarg82, and Deltakcs1 deletion strains, but not the Deltaipk1 deletion
      strain, had significantly reduced intracellular polyphosphate levels, suggesting
      that enzymes involved in inositol pyrophosphate synthesis are also required for
      polyphosphate accumulation.

PMID- 15866882
TI  - Identification of novel cytosolic phospholipase A(2)s, murine cPLA(2){delta},
      {epsilon}, and {zeta}, which form a gene cluster with cPLA(2){beta}.
AB  - Phospholipase A(2) hydrolyzes the sn-2 ester bond of glycerophospholipids that
      produce free fatty acids and lysophospholipids. Cytosolic phospholipase A(2)s
      (cPLA(2), group IV) are a subgroup of enzymes that act on the intracellular
      phospholipid membrane. The best investigated cPLA(2)alpha (group IVA) is a key
      enzyme for lipid mediator production in vivo. Here we report cloning and
      characterization of novel murine cPLA(2)s: cPLA(2)delta (group IVD),
      cPLA(2)epsilon (group IVE), and cPLA(2)zeta (group IVF), that form a gene cluster
      with cPLA(2)beta (group IVB). The deduced amino acid sequences of cPLA(2)delta,
      epsilon, and zeta demonstrated a conserved domain structure of cPLA(2), i.e. one
      C2 domain and one lipase domain. The potential catalytic dyad, Ser and Asp, was
      conserved for these newly cloned cPLA(2)s along with relatively high conservation
      for the surrounding residues. Transcripts of murine cPLA(2)delta, epsilon, and
      zeta appeared to be enriched in certain organs rather than ubiquitous
      distribution. Major Northern signals for cPLA(2)delta were detected in placenta,
      cPLA(2)epsilon in thyroid, heart, and skeletal muscle, and cPLA(2)zeta in
      thyroid. Recombinant proteins expressed in human embryonic kidney 293 cells
      demonstrated molecular sizes of about 100 kDa by Western blotting and exhibited
      Ca(2+)-dependent PLA(2) activities on 1-palmitoyl-2-[(14)C]arachidonoyl
      phosphatidylcholine substrate. In contrast to cPLA(2)alpha, cPLA(2)zeta preferred
      phosphatidylethanolamine to phosphatidylcholine. Intracellular localization was
      visualized by green fluorescent-tagged proteins. Each molecule showed specific
      localization, and cPLA(2)delta translocated from the cytosol to the perinuclear
      region by calcium-ionophore stimulation. We thus discovered these functional
      novel cPLA(2) genes, which cluster on murine chromosome 2E5.

PMID- 15866883
TI  - Characterization of a mouse second leukotriene B4 receptor, mBLT2: BLT2-dependent
      ERK activation and cell migration of primary mouse keratinocytes.
AB  - Leukotriene B4 (LTB4) is a potent chemoattractant and activator for granulocytes
      and macrophages and is considered to be an inflammatory mediator. Two G-protein
      coupled receptors for LTB4, BLT1 and BLT2, have been cloned from human and shown
      to be high and low affinity LTB4 receptors, respectively. To reveal the
      biological roles of BLT2 using mouse disease models, we cloned and characterized
      mouse BLT2. Chinese hamster ovary cells stably expressing mouse BLT2 exhibited
      specific binding to LTB4, LTB4-induced calcium mobilization, inhibition of
      adenylyl cyclase, and phosphorylation of extracellular signal-regulated kinase.
      We found that Compound A (4'-{[pentanoyl (phenyl) amino] methyl}-1, 1'-biphenyl-2
      carboxylic acid) was a BLT2-selective agonist and induced Ca(2+) mobilization and
      phosphorylation of extracellular signal-regulated kinase through BLT2, whereas it
      had no effect on BLT1. 12-epi LTB4 exhibited a partial agonistic activity against
      mBLT1 and mBLT2, whereas 6-trans-12-epi LTB4 did not. Northern blot analysis
      showed that mouse BLT2 is expressed highly in small intestine and skin in
      contrast to the ubiquitous expression of human BLT2. By in situ hybridization and
      the reverse transcriptase polymerase chain reaction, we demonstrated that mouse
      BLT2 is expressed in follicular and interfollicular keratinocytes. Compound A,
      LTB4, and 12-epi LTB4 all induced phosphorylation of extracellular signal
      regulated kinase in primary mouse keratinocytes. Furthermore, Compound A and LTB4
      induced chemotaxis in primary mouse keratinocytes. These data suggest the
      presence of functional BLT2 in primary keratinocytes.

PMID- 15866884
TI  - Src regulates distinct pathways for cell volume control through Vav and
      phospholipase Cgamma.
AB  - Cell volume recovery in response to swelling requires reorganization of the
      cytoskeleton and fluid efflux. We have previously shown that electrolyte and
      fluid efflux via K+ and Cl- channels is controlled by swelling-induced activation
      of phospholipase Cgamma (PLCgamma). Recently, integrin engagement has been
      suggested to trigger responses to swelling through activation of Rho family
      GTPases and Src kinases. Because both PLCgamma and Rho GTPases can be regulated
      by Src during integrin-mediated cytoskeletal reorganization, we sought to
      identify swelling-induced Src effectors. Upon hypotonic challenge, Src was
      rapidly activated in transient plasma membrane protrusions, where it colocalized
      with Vav, an activator of Rho GTPases. Inhibition of Src with PP2 attenuated
      phosphorylation of Vav. PP2 also attenuated phosphorylation of PLCgamma, and
      inhibited swelling-mediated activation of K+ and Cl- channels and cell volume
      recovery. These findings suggest that swelling-induced Src regulates cytoskeletal
      dynamics, through Vav, and fluid efflux, through PLCgamma, and thus can
      coordinate structural reorganization with fluid balance to maintain cellular
      integrity.

PMID- 15866886
TI  - Mnt-Max to Myc-Max complex switching regulates cell cycle entry.
AB  - The c-Myc oncoprotein is strongly induced during the G0 to S-phase transition and
      is an important regulator of cell cycle entry. In contrast to c-Myc, the putative
      Myc antagonist Mnt is maintained at a constant level during cell cycle entry. Mnt
      and Myc require interaction with Max for specific DNA binding at E-box sites, but
      have opposing transcriptional activities. Here, we show that c-Myc induction
      during cell cycle entry leads to a transient decrease in Mnt-Max complexes and a
      transient switch in the ratio of Mnt-Max to c-Myc-Max on shared target genes. Mnt
      overexpression suppressed cell cycle entry and cell proliferation, suggesting
      that the ratio of Mnt-Max to c-Myc-Max is critical for cell cycle entry.
      Furthermore, simultaneous Cre-Lox mediated deletion of Mnt and c-Myc in mouse
      embryo fibroblasts rescued the cell cycle entry and proliferative block caused by
      c-Myc ablation alone. These results demonstrate that Mnt-Myc antagonism plays a
      fundamental role in regulating cell cycle entry and proliferation.

PMID- 15866887
TI  - Impairment of starvation-induced and constitutive autophagy in Atg7-deficient
      mice.
AB  - Autophagy is a membrane-trafficking mechanism that delivers cytoplasmic
      constituents into the lysosome/vacuole for bulk protein degradation. This
      mechanism is involved in the preservation of nutrients under starvation condition
      as well as the normal turnover of cytoplasmic component. Aberrant autophagy has
      been reported in several neurodegenerative disorders, hepatitis, and myopathies.
      Here, we generated conditional knockout mice of Atg7, an essential gene for
      autophagy in yeast. Atg7 was essential for ATG conjugation systems and
      autophagosome formation, amino acid supply in neonates, and starvation-induced
      bulk degradation of proteins and organelles in mice. Furthermore, Atg7 deficiency
      led to multiple cellular abnormalities, such as appearance of concentric
      membranous structure and deformed mitochondria, and accumulation of ubiquitin
      positive aggregates. Our results indicate the important role of autophagy in
      starvation response and the quality control of proteins and organelles in
      quiescent cells.

PMID- 15866888
TI  - Insulin stimulates the halting, tethering, and fusion of mobile GLUT4 vesicles in
      rat adipose cells.
AB  - Glucose transport in adipose cells is regulated by changing the distribution of
      glucose transporter 4 (GLUT4) between the cell interior and the plasma membrane
      (PM). Insulin shifts this distribution by augmenting the rate of exocytosis of
      specialized GLUT4 vesicles. We applied time-lapse total internal reflection
      fluorescence microscopy to dissect intermediates of this GLUT4 translocation in
      rat adipose cells in primary culture. Without insulin, GLUT4 vesicles rapidly
      moved along a microtubule network covering the entire PM, periodically stopping,
      most often just briefly, by loosely tethering to the PM. Insulin halted this
      traffic by tightly tethering vesicles to the PM where they formed clusters and
      slowly fused to the PM. This slow release of GLUT4 determined the overall
      increase of the PM GLUT4. Thus, insulin initially recruits GLUT4 sequestered in
      mobile vesicles near the PM. It is likely that the primary mechanism of insulin
      action in GLUT4 translocation is to stimulate tethering and fusion of trafficking
      vesicles to specific fusion sites in the PM.

PMID- 15866889
TI  - Integrins control motile strategy through a Rho-cofilin pathway.
AB  - During wound healing, angiogenesis, and tumor invasion, cells often change their
      expression profiles of fibronectin-binding integrins. Here, we show that beta1
      integrins promote random migration, whereas beta3 integrins promote persistent
      migration in the same epithelial cell background. Adhesion to fibronectin by
      alpha(v)beta3 supports extensive actin cytoskeletal reorganization through the
      actin-severing protein cofilin, resulting in a single broad lamellipod with
      static cell-matrix adhesions at the leading edge. Adhesion by alpha5beta1 instead
      leads to the phosphorylation/inactivation of cofilin, and these cells fail to
      polarize their cytoskeleton but extend thin protrusions containing highly dynamic
      cell-matrix adhesions in multiple directions. The activity of the small GTPase
      RhoA is particularly high in cells adhering by alpha5beta1, and inhibition of Rho
      signaling causes a switch from a beta1- to a beta3-associated mode of migration,
      whereas increased Rho activity has the opposite effect. Thus, alterations in
      integrin expression profiles allow cells to modulate several critical aspects of
      the motile machinery through Rho GTPases.

PMID- 15866890
TI  - Coatomer-bound Cdc42 regulates dynein recruitment to COPI vesicles.
AB  - Cytoskeletal dynamics at the Golgi apparatus are regulated in part through a
      binding interaction between the Golgi-vesicle coat protein, coatomer, and the
      regulatory GTP-binding protein Cdc42 (Wu, W.J., J.W. Erickson, R. Lin, and R.A.
      Cerione. 2000. Nature. 405:800-804; Fucini, R.V., J.L. Chen, C. Sharma, M.M.
      Kessels, and M. Stamnes. 2002. Mol. Biol. Cell. 13:621-631). The precise role of
      this complex has not been determined. We have analyzed the protein composition of
      Golgi-derived coat protomer I (COPI)-coated vesicles after activating or
      inhibiting signaling through coatomer-bound Cdc42. We show that Cdc42 has
      profound effects on the recruitment of dynein to COPI vesicles. Cdc42, when bound
      to coatomer, inhibits dynein binding to COPI vesicles whereas preventing the
      coatomer-Cdc42 interaction stimulates dynein binding. Dynein recruitment was
      found to involve actin dynamics and dynactin. Reclustering of nocodazole
      dispersed Golgi stacks and microtubule/dynein-dependent ER-to-Golgi transport are
      both sensitive to disrupting Cdc42 mediated signaling. By contrast, dynein
      independent transport to the Golgi complex is insensitive to mutant Cdc42. We
      propose a model for how proper temporal regulation of motor-based vesicle
      translocation could be coupled to the completion of vesicle formation.

PMID- 15866891
TI  - STIM1, an essential and conserved component of store-operated Ca2+ channel
      function.
AB  - Store-operated Ca2+ (SOC) channels regulate many cellular processes, but the
      underlying molecular components are not well defined. Using an RNA interference
      (RNAi)-based screen to identify genes that alter thapsigargin (TG)-dependent Ca2+
      entry, we discovered a required and conserved role of Stim in SOC influx. RNAi
      mediated knockdown of Stim in Drosophila S2 cells significantly reduced TG
      dependent Ca2+ entry. Patch-clamp recording revealed nearly complete suppression
      of the Drosophila Ca2+ release-activated Ca2+ (CRAC) current that has biophysical
      characteristics similar to CRAC current in human T cells. Similarly, knockdown of
      the human homologue STIM1 significantly reduced CRAC channel activity in Jurkat T
      cells. RNAi-mediated knockdown of STIM1 inhibited TG- or agonist-dependent Ca2+
      entry in HEK293 or SH-SY5Y cells. Conversely, overexpression of STIM1 in HEK293
      cells modestly enhanced TG-induced Ca2+ entry. We propose that STIM1, a
      ubiquitously expressed protein that is conserved from Drosophila to mammalian
      cells, plays an essential role in SOC influx and may be a common component of SOC
      and CRAC channels.

PMID- 15866896
TI  - Spontaneous animal models of human disease.

PMID- 15866892
TI  - Capacitative calcium entry: sensing the calcium stores.
AB  - A long-standing mystery in the cell biology of calcium channel regulation is the
      nature of the signal linking intracellular calcium stores to plasma membrane
      capacitative calcium entry channels. An RNAi-based screen of selected Drosophila
      genes has revealed that a calcium-binding protein, stromal interaction molecule
      (STIM), plays an essential role in the activation of these channels and may be
      the long sought sensor of calcium store content.

PMID- 15866898
TI  - Suspected adverse reactions, 2004.

PMID- 15866899
TI  - Controlled clinical trial of the effect of a homoeopathic nosode on the somatic
      cell counts in the milk of clinically normal dairy cows.
AB  - Cows in a 250-cow Holstein-Friesian herd were allocated at random to be treated
      with either a homoeopathic nosode or a negative control, both treatments being
      applied by means of an aerosol spray to the vulval mucous membranes. A total of
      six treatments were given over a period of three days and milk samples were taken
      for the determination of somatic cell counts (SCC) on days -3, 3, 7, 9, 14, 21
      and 28. Individuals applying the treatments or carrying out the SCC determination
      were unaware of which animals were receiving which treatment. Owing to the wide
      natural variations in SCC, the trial had only a 71 per cent possibility of
      detecting a 30 per cent difference in SCC between the two groups. There were no
      significant differences between the SCC of the two groups on any sample day, but
      there were significant variations between the SCC on different days (P=0.003) in
      both groups.

PMID- 15866900
TI  - Long-term survival of 23 dogs with pericardial effusions.
AB  - Twenty-three dogs with pericardial effusions were identified from case records
      made between 1992 and 2000. Fourteen of the 23 were diagnosed with idiopathic
      pericardial effusions, and three of these were treated successfully by one
      pericardiocentesis. In the remaining 11 cases the pericardial effusion recurred;
      six cases were managed long-term by either two (three cases), three (two cases),
      or 11 repeated pericardiocenteses, and the remaining five were treated by
      pericardiectomy. The median survival time of the six dogs treated by repeated
      pericardiocentesis was five years and nine days.

PMID- 15866901
TI  - Linear hoof defects in sheep infected with foot-and-mouth disease.
AB  - During the epidemic of foot-and-mouth disease (FMD) in The Netherlands in 2001, a
      sheep farm was identified that had been subclinically infected with the disease.
      The FMD virus genome was detected in 12 of 16 probang samples collected from the
      sheep and the virus was isolated from four of these samples. Linear defects were
      observed, 1 to 3 cm from the coronary band, in the hooves of several of the
      sheep. The defects were thought to have been caused by the FMD infection. It was
      thought that the distance of the defects from the coronary band might be an
      indication of the time since the animals had been infected. To determine the
      growth rate of the claws of sheep, the growth of the hoof horn of uninfected
      lambs and ewes was measured; in the lambs the growth rate was 0.44 mm per day and
      in the ewes it was 0.29 mm per day.

PMID- 15866902
TI  - Non-pruritic granuloma in Norwegian forest cats.
AB  - The eosinophilic granuloma complex is a group of skin disorders common in cats.
      This paper describes the clinical, haematological and histopathological features
      of 17 related Norwegian forest cats, six of which had a linear granuloma on the
      caudal thigh, three of which also had a granuloma on the lower lip, and one of
      which had a granuloma in combination with an indolent ulcer. The high prevalence
      of the disease in this population is suggestive of a genetic background.

PMID- 15866903
TI  - Seroprevalence and significance of paramyxovirus titres in a zoological
      collection of lizards.

PMID- 15866904
TI  - Dentigerous cyst in a calf.

PMID- 15866905
TI  - Outbreak of salmonellosis in pigs with postweaning multisystemic wasting
      syndrome.

PMID- 15866906
TI  - Isolation of Brucella suis biovar 3 from horses in Croatia.

PMID- 15866907
TI  - Veterinary representation on RCVS VN Council.

PMID- 15866909
TI  - Teeth, bones and brushing.

PMID- 15866910
TI  - Change to greyhound rules of racing.

PMID- 15866911
TI  - Logos for the RCVS Practice Standards Scheme.

PMID- 15866912
TI  - Pyoverdine receptor: a case of positive Darwinian selection in Pseudomonas
      aeruginosa.

PMID- 15866913
TI  - Respiration and growth of Shewanella oneidensis MR-1 using vanadate as the sole
      electron acceptor.
AB  - Shewanella oneidensis MR-1 is a free-living gram-negative gamma-proteobacterium
      that is able to use a large number of oxidizing molecules, including fumarate,
      nitrate, dimethyl sulfoxide, trimethylamine N-oxide, nitrite, and insoluble iron
      and manganese oxides, to drive anaerobic respiration. Here we show that S.
      oneidensis MR-1 is able to grow on vanadate as the sole electron acceptor.
      Oxidant pulse experiments demonstrated that proton translocation across the
      cytoplasmic membrane occurs during vanadate reduction. Proton translocation is
      abolished in the presence of protonophores and the inhibitors 2-heptyl-4
      hydroxyquinoline N-oxide and antimycin A. Redox difference spectra indicated the
      involvement of membrane-bound menaquinone and cytochromes c, which was confirmed
      by transposon mutagenesis and screening for a vanadate reduction-deficient
      phenotype. Two mutants which are deficient in menaquinone synthesis were
      isolated. Another mutant with disruption in the cytochrome c maturation gene ccmA
      was unable to produce any cytochrome c and to grow on vanadate. This phenotype
      could be restored by complementation with the pEC86 plasmid expressing ccm genes
      from Escherichia coli. To our knowledge, this is the first report of E. coli ccm
      genes being functional in another organism. Analysis of an mtrB-deficient mutant
      confirmed the results of a previous paper indicating that OmcB may function as a
      vanadate reductase or may be part of a vanadate reductase complex.

PMID- 15866914
TI  - Protein engineering of the archetypal nitroarene dioxygenase of Ralstonia sp.
      strain U2 for activity on aminonitrotoluenes and dinitrotoluenes through alpha
      subunit residues leucine 225, phenylalanine 350, and glycine 407.
AB  - Naphthalene dioxygenase (NDO) from Ralstonia sp. strain U2 has not been reported
      to oxidize nitroaromatic compounds. Here, saturation mutagenesis of NDO at
      position F350 of the alpha-subunit (NagAc) created variant F350T that produced 3
      methyl-4-nitrocatechol from 2,6-dinitrotoluene (26DNT), that released nitrite
      from 23DNT sixfold faster than wild-type NDO, and that produced 3-amino-4-methyl
      5-nitrocatechol and 2-amino-4,6-dinitrobenzyl alcohol from 2-amino-4,6
      dinitrotoluene (2A46DNT) (wild-type NDO has no detectable activity on 26DNT and
      2A46DNT). DNA shuffling identified the beneficial NagAc mutation G407S, which
      when combined with the F350T substitution, increased the rate of NDO oxidation of
      26DNT, 23DNT, and 2A46DNT threefold relative to variant F350T. DNA shuffling of
      NDO nagAcAd also generated the NagAc variant G50S/L225R/A269T with an increased
      rate of 4-amino-2-nitrotoluene (4A2NT; reduction product of 2,4-dinitrotoluene)
      oxidation; from 4A2NT, this variant produced both the previously uncharacterized
      oxidation product 4-amino-2-nitrocresol (enhanced 11-fold relative to wild-type
      NDO) as well as 4-amino-2-nitrobenzyl alcohol (4A2NBA; wild-type NDO does not
      generate this product). G50S/L225R/A269T also had increased nitrite release from
      23DNT (14-fold relative to wild-type NDO) and generated 2,3-dinitrobenzyl alcohol
      (23DNBA) fourfold relative to wild-type NDO. The importance of position L225 for
      catalysis was confirmed through saturation mutagenesis; relative to wild-type
      NDO, NDO variant L225R had 12-fold faster generation of 4-amino-2-nitrocresol and
      production of 4A2NBA from 4A2NT as well as 24-fold faster generation of nitrite
      and 15-fold faster generation of 23DNBA from 23DNT. Hence, random mutagenesis
      discovered two new residues, G407 and L225, that influence the regiospecificity
      of Rieske non-heme-iron dioxygenases.

PMID- 15866915
TI  - Mosaic prophages with horizontally acquired genes account for the emergence and
      diversification of the globally disseminated M1T1 clone of Streptococcus
      pyogenes.
AB  - The recrudescence of severe invasive group A streptococcal (GAS) diseases has
      been associated with relatively few strains, including the M1T1 subclone that has
      shown an unprecedented global spread and prevalence and high virulence in
      susceptible hosts. To understand its unusual epidemiology, we aimed to identify
      unique genomic features that differentiate it from the fully sequenced M1 SF370
      strain. We constructed DNA microarrays from an M1T1 shotgun library and, using
      differential hybridization, we found that both M1 strains are 95% identical and
      that the 5% unique M1T1 clone sequences more closely resemble sequences found in
      the M3 strain, which is also associated with severe disease. Careful analysis of
      these unique sequences revealed three unique prophages that we named M1T1.X,
      M1T1.Y, and M1T1.Z. While M1T1.Y is similar to phage 370.3 of the M1-SF370
      strain, M1T1.X and M1T1.Z are novel and encode the toxins SpeA2 and Sda1,
      respectively. The genomes of these prophages are highly mosaic, with different
      segments being related to distinct streptococcal phages, suggesting that GAS
      phages continue to exchange genetic material. Bioinformatic and phylogenetic
      analyses revealed a highly conserved open reading frame (ORF) adjacent to the
      toxins in 18 of the 21 toxin-carrying GAS prophages. We named this ORF paratox,
      determined its allelic distribution among different phages, and found linkage
      disequilibrium between particular paratox alleles and specific toxin genes,
      suggesting that they may move as a single cassette. Based on the conservation of
      paratox and other genes flanking the toxins, we propose a recombination-based
      model for toxin dissemination among prophages. We also provide evidence that a
      minor population of the M1T1 clonal isolates have exchanged their virulence
      module on phage M1T1.Y, replacing it with a different module identical to that
      found on a related M3 phage. Taken together, the data demonstrate that mosaicism
      of the GAS prophages has contributed to the emergence and diversification of the
      M1T1 subclone.

PMID- 15866916
TI  - Persistence of Streptococcus pyogenes in stationary-phase cultures.
AB  - In addition to causing fulminant disease, Streptococcus pyogenes may be
      asymptomatically carried between recurrent episodes of pharyngitis. To better
      understand streptococcal carriage, we characterized in vitro long-term stationary
      phase survival (>4 weeks) of S. pyogenes. When grown in sugar-limited Todd-Hewitt
      broth, S. pyogenes cells remained culturable for more than 1 year. Both Todd
      Hewitt supplemented with excess glucose and chemically defined medium allowed
      survival for less than 1 week. After 4 weeks of survival in sugar-limited Todd
      Hewitt broth, at least 10(3) CFU per ml remained. When stained with fluorescent
      live-dead viability stain, there were a number of cells with intact membranes
      that were nonculturable. Under conditions that did not support persistence, these
      cells disappeared 2 weeks after loss of culturability. In persistent cultures,
      these may be cells that are dying during cell turnover. After more than 4 weeks
      in stationary phase, the culturable cells formed two alternative colony
      phenotypes: atypical large colonies and microcolonies. Protein expression in two
      independently isolated microcolony strains, from 14-week cultures, was examined
      by use of two-dimensional electrophoresis. The proteomes of these two strains
      exhibited extensive changes compared to the parental strain. While some of these
      changes were common to the two strains, many of the changes were unique to a
      single strain. Some of the common changes were in metabolic pathways, suggesting
      a possible alternate metabolism for the persisters. Overall, these data suggest
      that under certain in vitro conditions, S. pyogenes cells can persist for greater
      than 1 year as a dynamic population.

PMID- 15866917
TI  - Transcription activation in vitro by the Bradyrhizobium japonicum regulatory
      protein FixK2.
AB  - In Bradyrhizobium japonicum, the N2-fixing root nodule endosymbiont of soybean, a
      group of genes required for microaerobic, anaerobic, or symbiotic growth is
      controlled by FixK2, a key regulator that is part of the FixLJ-FixK2 cascade.
      FixK2 belongs to the family of cyclic AMP receptor protein/fumarate and nitrate
      reductase (CRP/FNR) transcription factors that recognize a palindromic DNA motif
      (CRP/FNR box) associated with the regulated promoters. Here, we report on a
      biochemical analysis of FixK2 and its transcription activation activity in vitro.
      FixK2 was expressed in Escherichia coli and purified as a soluble N-terminally
      histidine-tagged protein. Gel filtration experiments revealed that increasing the
      protein concentration shifts the monomer-dimer equilibrium toward the dimer.
      Purified FixK2 productively interacted with the B. japonicum sigma80-RNA
      polymerase holoenzyme, but not with E. coli sigma70-RNA polymerase holoenzyme, to
      activate transcription from the B. japonicum fixNOQP, fixGHIS, and hemN2
      promoters in vitro. Furthermore, FixK2 activated transcription from the E. coli
      FF(-41.5) model promoter, again only in concert with B. japonicum RNA polymerase.
      All of these promoters are so-called class II CRP/FNR-type promoters. We showed
      by specific mutagenesis that the FixK2 box at nucleotide position -40.5 in the
      hemN2 promoter, but not that at -78.5, is crucial for activation both in vivo and
      in vitro, which argues against recognition of a potential class III promoter.
      Given the lack of any evidence for the presence of a cofactor in purified FixK2,
      we surmise that FixK2 alone is sufficient to activate in vitro transcription to
      at least a basal level. This contrasts with all well-studied CRP/FNR-type
      proteins, which do require coregulators.

PMID- 15866918
TI  - Global transcriptional and proteomic analysis of the Sig1 heat shock regulon of
      Deinococcus radiodurans.
AB  - The sig1 gene, predicted to encode an extracytoplasmic function-type heat shock
      sigma factor of Deinococcus radiodurans, has been shown to play a central role in
      the positive regulation of the heat shock operons groESL and dnaKJ. To determine
      if Sig1 is required for the regulation of additional heat shock genes, we
      monitored the global transcriptional and proteomic profiles of a D. radiodurans
      R1 sig1 mutant and wild-type cells in response to elevated temperature stress.
      Thirty-one gene products were identified that showed heat shock induction in the
      wild type but not in the sig1 mutant. Quantitative real-time PCR experiments
      verified the transcriptional requirement of Sig1 for the heat shock induction of
      the mRNA of five of these genes-dnaK, groES, DR1314, pspA, and hsp20. hsp20
      appears to encode a new member of the small heat shock protein superfamily,
      DR1314 is predicted to encode a hypothetical protein with no recognizable
      orthologs, and pspA is predicted to encode a protein involved in maintenance of
      membrane integrity. Deletion mutation analysis demonstrated the importance in
      heat shock protection of hsp20 and DR1314. The promoters of dnaKJE, groESL,
      DR1314, pspA, and hsp20 were mapped and, combined with computer-based pattern
      searches of the upstream regions of the 26 other Sig1 regulon members, these
      results suggested that Sig1 might recognize both sigma70-type and sigma(W)-type
      promoter consensus sequences. These results expand the D. radiodurans Sig1 heat
      shock regulon to include 31 potential new members, including not only factors
      with cytoplasmic functions, such as groES and dnaK, but also those with
      extracytoplasmic functions, like pspA.

PMID- 15866919
TI  - Horizontal transfer of the high-pathogenicity island of Yersinia
      pseudotuberculosis.
AB  - The horizontal transfer of genetic elements plays a major role in bacterial
      evolution. The high-pathogenicity island (HPI), which codes for an iron uptake
      system, is present and highly conserved in various Enterobacteriaceae, suggesting
      its recent acquisition by lateral gene transfer. The aim of this work was to
      determine whether the HPI has kept its ability to be transmitted horizontally. We
      demonstrate here that the HPI is indeed transferable from a donor to a recipient
      Yersinia pseudotuberculosis strain. This transfer was observable only when the
      donor and recipient bacteria were cocultured at low temperatures in a liquid
      medium. When optimized conditions were used (bacteria actively growing in an iron
      deprived medium at 4 degrees C), the frequency of HPI transfer reached
      approximately 10(-8). The island was transferable to various serotype I strains
      of Y. pseudotuberculosis and to Yersinia pestis, but not to Y. pseudotuberculosis
      strains of serotypes II and IV or to Yersinia enterocolitica. Upon transfer, the
      HPI was inserted almost systematically into the asn3 tRNA locus. Acquisition of
      the HPI resulted in the loss of the resident island, suggesting an
      incompatibility between two copies of the HPI within the same strain. Transfer of
      the island did not require a functional HPI-borne insertion-excision machinery
      and was RecA dependent in the recipient but not the donor strain, suggesting that
      integration of the island into the recipient chromosome occurs via a mechanism of
      homologous recombination. This lateral transfer also involved the HPI-adjacent
      sequences, leading to the mobilization of a chromosomal region at least 46 kb in
      size.

PMID- 15866920
TI  - Defective O-antigen polymerization in tolA and pal mutants of Escherichia coli in
      response to extracytoplasmic stress.
AB  - We have previously shown that the TolA protein is required for the correct
      surface expression of the Escherichia coli O7 antigen lipopolysaccharide (LPS).
      In this work, delta tolA and delta pal mutants of E. coli K-12 W3110 were
      transformed with pMF19 (encoding a rhamnosyltransferase that reconstitutes the
      expression of O16-specific LPS), pWQ5 (encoding the Klebsiella pneumoniae O1 LPS
      gene cluster), or pWQ802 (encoding the genes necessary for the synthesis of
      Salmonella enterica O:54). Both DeltatolA and delta pal mutants exhibited reduced
      surface expression of O16 LPS as compared to parental W3110, but no significant
      differences were observed in the expression of K. pneumoniae O1 LPS and S.
      enterica O:54 LPS. Therefore, TolA and Pal are required for the correct surface
      expression of O antigens that are assembled in a wzy (polymerase)-dependent
      manner (like those of E. coli O7 and O16) but not for O antigens assembled by wzy
      independent pathways (like K. pneumoniae O1 and S. enterica O:54). Furthermore,
      we show that the reduced surface expression of O16 LPS in delta tolA and delta
      pal mutants was associated with a partial defect in O-antigen polymerization and
      it was corrected by complementation with intact tolA and pal genes, respectively.
      Using derivatives of W3110 delta tolA and W3110 delta pal containing lacZ
      reporter fusions to fkpA and degP, we also demonstrate that the RpoE-mediated
      extracytoplasmic stress response is upregulated in these mutants. Moreover, an
      altered O16 polymerization was also detected under conditions that stimulate RpoE
      mediated extracytoplasmic stress responses in tol+ and pal+ genetic backgrounds.
      A Wzy derivative with an epitope tag at the C-terminal end of the protein was
      stable in all the mutants, ruling out stress-mediated proteolysis of Wzy. We
      conclude that the absence of TolA and Pal elicits a sustained extracytoplasmic
      stress response that in turn reduces O-antigen polymerization but does not affect
      the stability of the Wzy O-antigen polymerase.

PMID- 15866921
TI  - Plasmid partition system of the P1par family from the pWR100 virulence plasmid of
      Shigella flexneri.
AB  - P1par family members promote the active segregation of a variety of plasmids and
      plasmid prophages in gram-negative bacteria. Each has genes for ParA and ParB
      proteins, followed by a parS partition site. The large virulence plasmid pWR100
      of Shigella flexneri contains a new P1par family member: pWR100par. Although
      typical parA and parB genes are present, the putative pWR100parS site is atypical
      in sequence and organization. However, pWR100parS promoted accurate plasmid
      partition in Escherichia coli when the pWR100 Par proteins were supplied. Unique
      BoxB hexamer motifs within parS define species specificities among previously
      described family members. Although substantially different from P1parS from the
      P1 plasmid prophage of E. coli, pWR100parS has the same BoxB sequence. As
      predicted, the species specificity of the two types proved identical. They also
      shared partition-mediated incompatibility, consistent with the proposed
      mechanistic link between incompatibility and species specificity. Among several
      informative sequence differences between pWR100parS and P1parS is the presence of
      a 21-bp insert at the center of the pWR100parS site. Deletion of this insert left
      much of the parS activity intact. Tolerance of central inserts with integral
      numbers of helical DNA turns reflects the critical topology of these sites, which
      are bent by binding the host IHF protein.

PMID- 15866922
TI  - A novel 3-deoxy-D-manno-octulosonic acid (Kdo) hydrolase that removes the outer
      Kdo sugar of Helicobacter pylori lipopolysaccharide.
AB  - The lipid A domain anchors lipopolysaccharide (LPS) to the outer membrane and is
      typically a disaccharide of glucosamine that is both acylated and phosphorylated.
      The core and O-antigen carbohydrate domains are linked to the lipid A moiety
      through the eight-carbon sugar 3-deoxy-D-manno-octulosonic acid known as Kdo.
      Helicobacter pylori LPS has been characterized as having a single Kdo residue
      attached to lipid A, predicting in vivo a monofunctional Kdo transferase (WaaA).
      However, using an in vitro assay system we demonstrate that H. pylori WaaA is a
      bifunctional enzyme transferring two Kdo sugars to the tetra-acylated lipid A
      precursor lipid IV(A). In the present work we report the discovery of a Kdo
      hydrolase in membranes of H. pylori capable of removing the outer Kdo sugar from
      Kdo2-lipid A. Enzymatic removal of the Kdo group was dependent upon prior removal
      of the 1-phosphate group from the lipid A domain, and mass spectrometric analysis
      of the reaction product confirmed the enzymatic removal of a single Kdo residue
      by the Kdo-trimming enzyme. This is the first characterization of a Kdo hydrolase
      involved in the modification of gram-negative bacterial LPS.

PMID- 15866923
TI  - In vitro characterization of the Bacillus subtilis protein tyrosine phosphatase
      YwqE.
AB  - Both gram-negative and gram-positive bacteria possess protein tyrosine
      phosphatases (PTPs) with a catalytic Cys residue. In addition, many gram-positive
      bacteria have acquired a new family of PTPs, whose first characterized member was
      CpsB from Streptococcus pneumoniae. Bacillus subtilis contains one such CpsB-like
      PTP, YwqE, in addition to two class II Cys-based PTPs, YwlE and YfkJ. The
      substrates for both YwlE and YfkJ are presently unknown, while YwqE was shown to
      dephosphorylate two phosphotyrosine-containing proteins implicated in UDP
      glucuronate biosynthesis, YwqD and YwqF. In this study, we characterize YwqE,
      compare the activities of the three B. subtilis PTPs (YwqE, YwlE, and YfkJ), and
      demonstrate that the two B. subtilis class II PTPs do not dephosphorylate the
      physiological substrates of YwqE.

PMID- 15866924
TI  - Identification of cptA, a PmrA-regulated locus required for phosphoethanolamine
      modification of the Salmonella enterica serovar typhimurium lipopolysaccharide
      core.
AB  - In response to the in vivo environment, the Salmonella enterica serovar
      Typhimurium lipopolysaccharide (LPS) is modified. These modifications are
      controlled in part by the two-component regulatory system PmrA-PmrB, with the
      addition of 4-aminoarabinose (Ara4N) to the lipid A and phosphoethanolamine
      (pEtN) to the lipid A and core. Here we demonstrate that the PmrA-regulated
      STM4118 (cptA) gene is necessary for the addition of pEtN to the LPS core. pmrC,
      a PmrA-regulated gene necessary for the addition of pEtN to lipid A, did not
      affect core pEtN addition. Although imparting a similar surface charge
      modification as Ara4N, which greatly affects polymyxin B resistance and murine
      virulence, neither pmrC nor cptA plays a dramatic role in antimicrobial peptide
      resistance in vitro or virulence in the mouse model. Therefore, factors other
      than surface charge/electrostatic interaction contribute to resistance to
      antimicrobial peptides such as polymyxin B.

PMID- 15866925
TI  - Mechanisms of strand replacement synthesis for plasmid DNA transferred by
      conjugation.
AB  - A single strand of plasmid DNA is transferred during conjugation. We examined the
      mechanism of complementary strand synthesis in recipient cells following
      conjugative mobilization of derivatives of the IncQ plasmid R1162. A system for
      electroporation of donor cells, followed by immediate mating, was used to
      eliminate plasmid-specific replicative functions. Under these conditions,
      Escherichia coli recipients provided a robust mechanism for initiation of
      complementary strand synthesis on transferred DNA. In contrast, plasmid functions
      were important for efficient strand replacement in recipient cells of Salmonella
      enterica serovar Typhimurium. The mobilizing vector for R1162 transfer, the IncP1
      plasmid R751, encodes a DNA primase with low specificity for initiation. This
      protein increased the frequency of transfer of R751 into Salmonella, but despite
      its low specificity, it was inactive on the R1162 derivatives. The R751 primase
      was slightly inhibitory for the transfer of both R751 and R1162 into E. coli. The
      results show that there is a chromosomally encoded mechanism for complementary
      strand synthesis of incoming transferred DNA in E. coli, while plasmid-specific
      mechanisms for this synthesis are important in Salmonella.

PMID- 15866926
TI  - The RssAB two-component signal transduction system in Serratia marcescens
      regulates swarming motility and cell envelope architecture in response to
      exogenous saturated fatty acids.
AB  - Serratia marcescens swarms at 30 degrees C but not at 37 degrees C on a nutrient
      rich (LB) agar surface. Mini-Tn5 mutagenesis of S. marcescens CH-1 yielded a
      mutant (WC100) that swarms not only vigorously at 37 degrees C but also earlier
      and faster than the parent strain swarms at 30 degrees C. Analysis of this mutant
      revealed that the transposon was inserted into a gene (rssA) predicted to encode
      a bacterial two-component signal transduction sensor kinase, upstream of which a
      potential response regulator gene (rssB) was located. rssA and rssB insertion
      deletion mutants were constructed through homologous recombination, and the two
      mutants exhibited similar swarming phenotypes on LB swarming agar, in which
      swarming not only occurred at 37 degrees C but also initiated at a lower cell
      density, on a surface with a higher agar concentration, and more rapidly than the
      swarming of the parent strain at 30 degrees C. Both mutants also exhibited
      increased hemolysin activity and altered cell surface topologies compared with
      the parent CH-1 strain. Temperature and certain saturated fatty acids (SFAs) were
      found to negatively regulate S. marcescens swarming via the action of RssA-RssB.
      Analysis of the fatty acid profiles of the parent and the rssA and rssB mutants
      grown at 30 degrees C or 37 degrees C and under different nutrition conditions
      revealed a relationship between cellular fatty acid composition and swarming
      phenotypes. The cellular fatty acid profile was also observed to be affected by
      RssA and RssB. SFA-dependent inhibition of swarming was also observed in Proteus
      mirabilis, suggesting that either SFAs per se or the modulation of cellular fatty
      acid composition and hence homeostasis of membrane fluidity may be a conserved
      mechanism for regulating swarming motility in gram-negative bacteria.

PMID- 15866927
TI  - Role of Mycobacterium tuberculosis Ser/Thr kinase PknF: implications in glucose
      transport and cell division.
AB  - Protein kinases have a diverse array of functions in bacterial physiology, with a
      distinct role in the regulation of development, stress responses, and
      pathogenicity. pknF, one of the 11 kinases of Mycobacterium tuberculosis, encodes
      an autophosphorylating, transmembrane serine/threonine protein kinase, which is
      absent in the fast-growing, nonpathogenic Mycobacterium smegmatis. Herein, we
      investigate the physiological role of PknF using an antisense strategy with M.
      tuberculosis and expressing PknF and its kinase mutant (K41M) in M. smegmatis.
      Expression of PknF in M. smegmatis led to reduction in the growth rate and
      shortening and swelling of cells with constrictions. Interestingly, an antisense
      strain of M. tuberculosis expressing a low level of PknF displayed fast growth
      and a deformed cell morphology compared to the wild-type strain. Electron
      microscopy showed that most of the cells of the antisense strain were of a
      smaller size with an aberrant septum. Furthermore, nutrient transport analysis of
      these strains was conducted using 3H-labeled and 14C-labeled substrates. A
      significant increase in the uptake of D-glucose but not of glycerol, leucine, or
      oleic acid was observed in the antisense strain compared to the wild-type strain.
      The results suggest that PknF plays a direct/indirect role in the regulation of
      glucose transport, cell growth, and septum formation in M. tuberculosis.

PMID- 15866928
TI  - CrgA is an inducible LysR-type regulator of Neisseria meningitidis, acting both
      as a repressor and as an activator of gene transcription.
AB  - The crgA gene of Neisseria meningitidis, which codes for a LysR-type regulator,
      is divergently oriented with respect to the mdaB gene, which codes for a
      hypothetical NADPH-quinone oxidoreductase. Transcriptional studies of the
      intergenic region between crgA and mdaB showed that two overlapping and divergent
      promoters, P(crgA) and P(mdaB), control transcription of these genes. Deletion of
      the crgA gene led to a strong increase in transcription from the P(crgA) promoter
      and a concomitant strong decrease in transcription from the P(mdaB) promoter,
      indicating that CrgA acts both as an autorepressor of transcription at its own
      promoter and as an activator of transcription at the mdaB promoter. Addition of
      alpha-methylene-gamma-butyrolactone (MBL), an inducer of NADPH-quinone
      oxidoreductase, to wild-type N. meningitidis cells specifically resulted in
      further activation of transcription of the P(mdaB) promoter and more repression
      of transcription of the P(crgA) promoter. No such regulation was observed when
      MBL was added to crgA-deficient cells, indicating that the transcriptional
      response to MBL is CrgA mediated. Under the same experimental conditions, no
      regulation of transcription by either CrgA or MBL was detected at the pilus and
      capsule genes. The role of CrgA in the regulation of gene expression during the
      infectious cycle of N. meningitidis is discussed.

PMID- 15866929
TI  - Piv site-specific invertase requires a DEDD motif analogous to the catalytic
      center of the RuvC Holliday junction resolvases.
AB  - Piv, a unique prokaryotic site-specific DNA invertase, is related to transposases
      of the insertion elements from the IS110/IS492 family and shows no similarity to
      the site-specific recombinases of the tyrosine- or serine-recombinase families.
      Piv tertiary structure is predicted to include the RNase H-like fold that
      typically encompasses the catalytic site of the recombinases or nucleases of the
      retroviral integrase superfamily, including transposases and RuvC-like Holliday
      junction resolvases. Analogous to the DDE and DEDD catalytic motifs of
      transposases and RuvC, respectively, four Piv acidic residues D9, E59, D101, and
      D104 appear to be positioned appropriately within the RNase H fold to coordinate
      two divalent metal cations. This suggests mechanistic similarity between site
      specific inversion mediated by Piv and transposition or endonucleolytic reactions
      catalyzed by enzymes of the retroviral integrase superfamily. The role of the
      DEDD motif in Piv catalytic activity was addressed using Piv variants that are
      substituted individually or multiply at these acidic residues and assaying for in
      vivo inversion, intermolecular recombination, and DNA binding activities. The
      results indicate that all four residues of the DEDD motif are required for Piv
      catalytic activity. The DEDD residues are not essential for inv recombination
      site recognition and binding, but this acidic tetrad does appear to contribute to
      the stability of Piv-inv interactions. On the basis of these results, a working
      model for Piv-mediated inversion that includes resolution of a Holliday junction
      is presented.

PMID- 15866930
TI  - The iron-regulated iupABC operon is required for saprophytic growth of the
      intracellular pathogen Rhodococcus equi at low iron concentrations.
AB  - Rhodococcus equi is a facultative intracellular pathogen which proliferates
      rapidly in both manure-enriched soil and alveolar macrophages. Although both
      environments are characterized by extremely low concentrations of free iron, very
      little is known regarding the strategies employed by R. equi to thrive under
      these conditions. This paper reports the characterization of an R. equi
      transposome mutant that fails to grow at low iron concentrations. The transposome
      was shown to be inserted into iupA, the first gene of the iupABC operon encoding
      an ABC transport system highly similar to siderophore uptake systems. Disruption
      of the iupA gene also resulted in a failure of R. equi to utilize heme and
      hemoglobin as a source of iron. Introduction of the iupABC operon in trans
      restored the wild-type phenotype of the mutant strain. iupABC transcripts were
      180-fold more abundant in R. equi grown in iron-depleted medium than in organisms
      grown in iron-replete medium. Proliferation of the iupABC mutant strain in
      macrophages was comparable to that of the wild-type strain. Furthermore, the
      iupABC mutant was not attenuated in mice, showing that the iupABC operon is not
      required for virulence.

PMID- 15866931
TI  - The repA gene of the linear Yersinia enterocolitica prophage PY54 functions as a
      circular minimal replicon in Escherichia coli.
AB  - The Yersinia enterocolitica prophage PY54 replicates as a linear DNA molecule
      with covalently closed ends. For replication of a circular PY54 minimal replicon
      that has been derived from a linear minireplicon, two phage-encoded loci are
      essential in Escherichia coli: (i) the reading frame of the replication
      initiation gene repA and (ii) its 212-bp origin located within the 3' portion of
      repA. The RepA protein acts in trans on the origin since we have physically
      separated the PY54 origin and repA onto a two-plasmid origin test system. For
      this trans action, the repA 3' end carrying the origin is dispensable.
      Mutagenesis by alanine scan demonstrated that the motifs for primase and for
      nucleotide binding present in the protein are essential for RepA activity. The
      replication initiation functions of RepA are replicon specific. The replication
      initiation proteins DnaA, DnaG, and DnaB of the host are unable to promote origin
      replication in the presence of mutant RepA proteins that carry single residue
      exchanges in these motifs. The proposed origins of the known related hairpin
      prophages PY54, N15, and PKO2 are all located toward the 3' end of the
      corresponding repA genes, where several structure elements are conserved. Origin
      function depends on the integrity of these elements.

PMID- 15866932
TI  - Role of mutS and mutL genes in hypermutability and recombination in
      Staphylococcus aureus.
AB  - The mutator phenotype has been linked in several bacterial genera to a defect in
      the methyl-mismatch repair system, in which the major components are MutS and
      MutL. This system is involved both in mismatch repair and in prevention of
      recombination between homeologous fragments in Escherichia coli and has been
      shown to play an important role in the adaptation of bacterial populations in
      changing and stressful environments. In this report we describe the molecular
      analysis of the mutS and mutL genes of Staphylococcus aureus. A genetic analysis
      of the mutSL region was performed in S. aureus RN4220. Reverse transcriptase PCR
      experiments confirmed the operon structure already reported in other gram
      positive organisms. Insertional inactivation of mutS and mutL genes and
      complementation showed the role of both genes in hypermutability in this species.
      We also designed an in vitro model to study the role of MutS and MutL in
      homeologous recombination in S. aureus. For this purpose, we constructed a bank
      of S. aureus RN4220 and mutS and mutL mutants containing the integrative
      thermosensitive vector pBT1 in which fragments with various levels of identity
      (74% to 100%) to the S. aureus sodA gene were cloned. MutS and MutL proteins
      seemed to have a limited effect on the control of homeologous recombination.
      Sequence of mutS and mutL genes was analyzed in 11 hypermutable S. aureus
      clinical isolates. In four of five isolates with mutated or deleted mutS or mutL
      genes, a relationship between alterations and mutator phenotypes could be
      established by negative complementation of the mutS or mutL mutants.

PMID- 15866933
TI  - YojI of Escherichia coli functions as a microcin J25 efflux pump.
AB  - In the present study, we showed that yojI, an Escherichia coli open reading frame
      with an unknown function, mediates resistance to the peptide antibiotic microcin
      J25 when it is expressed from a multicopy vector. Disruption of the single
      chromosomal copy of yojI increased sensitivity of cells to microcin J25. The YojI
      protein was previously assumed to be an ATP-binding-cassette-type exporter on the
      basis of sequence similarities. We demonstrate that YojI is capable of pumping
      out microcin molecules. Thus, one obvious explanation for the protective effect
      against microcin J25 is that YojI action keeps the intracellular concentration of
      the peptide below a toxic level. The outer membrane protein TolC in addition to
      YojI is required for export of microcin J25 out of the cell. Microcin J25 is thus
      the first known substrate for YojI.

PMID- 15866934
TI  - Operation of the CO dehydrogenase/acetyl coenzyme A pathway in both acetate
      oxidation and acetate formation by the syntrophically acetate-oxidizing bacterium
      Thermacetogenium phaeum.
AB  - Thermacetogenium phaeum is a homoacetogenic bacterium that can grow on various
      substrates, such as pyruvate, methanol, or H2/CO2. It can also grow on acetate if
      cocultured with the hydrogen-consuming methanogenic partner Methanothermobacter
      thermautotrophicus. Enzyme activities of the CO dehydrogenase/acetyl coenzyme A
      (CoA) pathway (CO dehydrogenase, formate dehydrogenase, formyl tetrahydrofolate
      synthase, methylene tetrahydrofolate dehydrogenase) were detected in cell
      extracts of pure cultures and of syntrophic cocultures. Mixed cell suspensions of
      T. phaeum and M. thermautotrophicus oxidized acetate rapidly and produced acetate
      after addition of H2/CO2 after a short time lag. CO dehydrogenase activity
      staining after native polyacrylamide gel electrophoresis exhibited three oxygen
      labile bands which were identical in pure culture and coculture. Protein profiles
      of T. phaeum cells after sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis indicated that the strain exhibited basically the same protein
      patterns in both pure and syntrophic culture. These results indicate that T.
      phaeum operates the CO dehydrogenase/acetyl-CoA pathway reversibly both in
      acetate oxidation and in reductive acetogenesis by using the same biochemical
      apparatus, although it has to couple this pathway to ATP synthesis in different
      ways.

PMID- 15866935
TI  - Biofilm formation and sloughing in Serratia marcescens are controlled by quorum
      sensing and nutrient cues.
AB  - We describe here a role for quorum sensing in the detachment, or sloughing, of
      Serratia marcescens filamentous biofilms, and we show that nutrient conditions
      affect the biofilm morphotype. Under reduced carbon or nitrogen conditions, S.
      marcescens formed a classical biofilm consisting of microcolonies. The
      filamentous biofilm could be converted to a microcolony-type biofilm by switching
      the medium after establishment of the biofilm. Similarly, when initially grown as
      a microcolony biofilm, S. marcescens could be converted back to a filamentous
      biofilm by increasing the nutrient composition. Under high-nutrient conditions,
      an N-acyl homoserine lactone quorum-sensing mutant formed biofilms that were
      indistinguishable from the wild-type biofilms. Similarly, other quorum-sensing
      dependent behaviors, such as swarming motility, could be rendered quorum sensing
      independent by manipulating the growth medium. Quorum sensing was also found to
      be involved in the sloughing of the filamentous biofilm. The biofilm formed by
      the bacterium consistently sloughed from the substratum after approximately 75 to
      80 h of development. The quorum-sensing mutant, when supplemented with exogenous
      signal, formed a wild-type filamentous biofilm and sloughed at the same time as
      the wild type, and this was independent of surfactant production. When we removed
      the signal from the quorum-sensing mutant prior to the time of sloughing, the
      biofilm did not undergo significant detachment. Together, the data suggest that
      biofilm formation by S. marcescens is a dynamic process that is controlled by
      both nutrient cues and the quorum-sensing system.

PMID- 15866936
TI  - Agrobacterium tumefaciens VirB9, an outer-membrane-associated component of a type
      IV secretion system, regulates substrate selection and T-pilus biogenesis.
AB  - Agrobacterium tumefaciens translocates DNA and protein substrates between cells
      via a type IV secretion system (T4SS) whose channel subunits include the VirD4
      coupling protein, VirB11 ATPase, VirB6, VirB8, VirB2, and VirB9. In this study,
      we used linker insertion mutagenesis to characterize the contribution of the
      outer-membrane-associated VirB9 to assembly and function of the VirB/D4 T4SS.
      Twenty-five dipeptide insertion mutations were classified as permissive for
      intercellular substrate transfer (Tra+), completely transfer defective (Tra-), or
      substrate discriminating, e.g., selectively permissive for transfer only of the
      oncogenic transfer DNA and the VirE2 protein substrates or of a mobilizable IncQ
      plasmid substrate. Mutations inhibiting transfer of DNA substrates did not affect
      formation of close contacts of the substrate with inner membrane channel subunits
      but blocked formation of contacts with the VirB2 and VirB9 channel subunits,
      which is indicative of a defect in assembly or function of the distal portion of
      the secretion channel. Several mutations in the N- and C-terminal regions
      disrupted VirB9 complex formation with the outer-membrane-associated lipoprotein
      VirB7 or the inner membrane energy sensor VirB10. Several VirB9.i2-producing Tra+
      strains failed to elaborate T pilus at detectable levels (Pil-), and three such
      Tra+ Pil- mutant strains were rendered Tra- upon deletion of virB2, indicating
      that the cellular form of pilin protein is essential for substrate translocation.
      Our findings, together with computer-based analyses, support a model in which
      distinct domains of VirB9 contribute to substrate selection and translocation,
      establishment of channel subunit contacts, and T-pilus biogenesis.

PMID- 15866937
TI  - Solution structure of the carbon storage regulator protein CsrA from Escherichia
      coli.
AB  - The carbon storage regulator A (CsrA) is a protein responsible for the repression
      of a variety of stationary-phase genes in bacteria. In this work, we describe the
      nuclear magnetic resonance (NMR)-based structure of the CsrA dimer and its RNA
      binding properties. CsrA is a dimer of two identical subunits, each composed of
      five strands, a small alpha-helix and a flexible C terminus. NMR titration
      experiments suggest that the beta1-beta2 and beta3-beta4 loops and the C-terminal
      helix are important elements in RNA binding. Even though the beta3-beta4 loop
      contains a highly conserved RNA-binding motif, GxxG, typical of KH domains, our
      structure excludes CsrA from being a member of this protein family, as previously
      suggested. A mechanism for the recognition of mRNAs downregulated by CsrA is
      proposed.

PMID- 15866938
TI  - Identification of a 521-kilodalton protein (Gli521) involved in force generation
      or force transmission for Mycoplasma mobile gliding.
AB  - Several mycoplasma species are known to glide on solid surfaces such as glass in
      the direction of the membrane protrusion, but the mechanism underlying this
      movement is unknown. To identify a novel protein involved in gliding, we raised
      monoclonal antibodies against a detergent-insoluble protein fraction of
      Mycoplasma mobile, the fastest glider, and screened the antibodies for inhibitory
      effects on gliding. Five monoclonal antibodies stopped the movement of gliding
      mycoplasmas, keeping them on the glass surface, and all of them recognized a
      large protein in immunoblotting. This protein, named Gli521, is composed of 4,738
      amino acids, has a predicted molecular mass of 520,559 Da, and is coded
      downstream of a gene for another gliding protein, Gli349, which is known to be
      responsible for glass binding during gliding. Edman degradation analysis
      indicated that the N-terminal region is processed at the peptide bond between the
      amino acid residues at positions 43 and 44. Analysis of gliding mutants isolated
      previously revealed that the Gli521 protein is missing in a nonbinding mutant,
      m9, where the gli521 gene is truncated by a nonsense mutation at the codon for
      the amino acid at position 1170. Immunofluorescence and immunoelectron microscopy
      indicated that Gli521 localizes all around the base of the membrane protrusion,
      at the "neck," as previously observed for Gli349. Analysis of the inhibitory
      effects of the anti-Gli521 antibody on gliding motility revealed that this
      protein is responsible for force generation or force transmission, a role
      distinct from that of Gli349, and also suggested conformational changes of Gli349
      and Gli521 during gliding.

PMID- 15866939
TI  - Genetic dissection of the sporulation protein SpoIIE and its role in asymmetric
      division in Bacillus subtilis.
AB  - SpoIIE is a dual-function protein in Bacillus subtilis that contributes to the
      switch from medial to polar cell division during sporulation and is responsible
      for activating the cell-specific transcription factor sigma(F). SpoIIE consists
      of an N-terminal domain with 10 membrane-spanning segments (region I), a C
      terminal phosphatase domain (region III), and a central domain (region II) of
      uncertain function. To investigate the role of SpoIIE in polar division, we took
      advantage of a system for efficiently producing polar septa during growth in a
      SpoIIE-dependent manner using cells engineered to produce the sporulation protein
      in response to an inducer. The results show that regions II and III play a
      critical role in polar septum formation and that specific amino acid
      substitutions in those regions affect the abilities of SpoIIE both to promote
      polar division and to localize to the division machinery. Additionally, we show
      that neither the phosphatase function of SpoIIE nor the N-terminal, membrane
      spanning region is needed for the switch to asymmetric division.

PMID- 15866940
TI  - The linear double-stranded DNA of phage Bam35 enters lysogenic host cells, but
      the late phage functions are suppressed.
AB  - Bam35, a temperate double-stranded DNA bacteriophage with a 15-kb linear genome,
      infects gram-positive Bacillus thuringiensis cells. Bam35 morphology and genome
      organization resemble those of PRD1, a lytic phage infecting gram-negative
      bacteria. Bam35 and PRD1 have an outer protein coat surrounding a membrane that
      encloses the viral DNA. We used electrochemical methods to investigate
      physiological changes of the lysogenic and nonlysogenic hosts during Bam35 DNA
      entry and host cell lysis. During viral DNA entry, there was an early temporal
      decrease of membrane voltage associated with K+ efflux that took place when
      either lysogenic or nonlysogenic hosts were infected. Approximately 40 min
      postinfection, a second strong K+ efflux was registered that was proposed to be
      associated with the insertion of holin molecules into the plasma membrane. This
      phenomenon occurred only when nonlysogenic cells were infected. Lysogenic hosts
      rarely were observed entering the lytic cycle as demonstrated by thin-section
      electron microscopy.

PMID- 15866941
TI  - Structural and functional divergence of MutS2 from bacterial MutS1 and eukaryotic
      MSH4-MSH5 homologs.
AB  - MutS homologs, identified in nearly all bacteria and eukaryotes, include the
      bacterial proteins MutS1 and MutS2 and the eukaryotic MutS homologs 1 to 7, and
      they often are involved in recognition and repair of mismatched bases and small
      insertion/deletions, thereby limiting illegitimate recombination and spontaneous
      mutation. To explore the relationship of MutS2 to other MutS homologs, we
      examined conserved protein domains. Fundamental differences in structure between
      MutS2 and other MutS homologs suggest that MutS1 and MutS2 diverged early during
      evolution, with all eukaryotic homologs arising from a MutS1 ancestor. Data from
      MutS1 crystal structures, biochemical results from MutS2 analyses, and our
      phylogenetic studies suggest that MutS2 has functions distinct from other members
      of the MutS family. A mutS2 mutant was constructed in Helicobacter pylori, which
      lacks mutS1 and mismatch repair genes mutL and mutH. We show that MutS2 plays no
      role in mismatch or recombinational repair or deletion between direct DNA
      repeats. In contrast, MutS2 plays a significant role in limiting intergenomic
      recombination across a range of donor DNA tested. This phenotypic analysis is
      consistent with the phylogenetic and biochemical data suggesting that MutS1 and
      MutS2 have divergent functions.

PMID- 15866943
TI  - Severity of the streptomycin resistance and streptomycin dependence phenotypes of
      ribosomal protein S12 of Thermus thermophilus depends on the identity of highly
      conserved amino acid residues.
AB  - The structural basis for the streptomycin dependence phenotype of ribosomal
      protein S12 mutants is poorly understood. Here we describe the application of
      site-directed mutagenesis and gene replacement of Thermus thermophilus rpsL to
      assess the importance of side chain identity and tertiary interactions as
      phenotypic determinants of drug-dependent mutants.

PMID- 15866942
TI  - Gyrase inhibitors and thymine starvation disrupt the normal pattern of plasmid
      RK2 localization in Escherichia coli.
AB  - Multicopy plasmids in Escherichia coli are not randomly distributed throughout
      the cell but exist as defined clusters that are localized at the mid-cell, or at
      the 1/4 and 3/4 cell length positions. To explore the factors that contribute to
      plasmid clustering and localization, E. coli cells carrying a plasmid RK2
      derivative that can be tagged with a green fluorescent protein-LacI fusion
      protein were subjected to various conditions that interfere with plasmid
      superhelicity and/or DNA replication. The various treatments included thymine
      starvation and the addition of the gyrase inhibitors nalidixic acid and
      novobiocin. In each case, localization of plasmid clusters at the preferred
      positions was disrupted but the plasmids remained in clusters, suggesting that
      normal plasmid superhelicity and DNA synthesis in elongating cells are not
      required for the clustering of individual plasmid molecules. It was also observed
      that the inhibition of DNA replication by these treatments produced filaments in
      which the plasmid clusters were confined to one or two nucleoid bodies, which
      were located near the midline of the filament and were not evenly spaced
      throughout the filament, as is found in cells treated with cephalexin. Finally,
      the enhanced yellow fluorescent protein-RarA fusion protein was used to localize
      the replication complex in individual E. coli cells. Novobiocin and nalidixic
      acid treatment both resulted in rapid loss of RarA foci. Under these conditions
      the RK2 plasmid clusters were not disassembled, suggesting that a completely
      intact replication complex is not required for plasmid clustering.

PMID- 15866944
TI  - Virulence and the environment: a novel role for Vibrio cholerae toxin-coregulated
      pili in biofilm formation on chitin.
AB  - The toxin-coregulated pilus (TCP) of Vibrio cholerae is required for intestinal
      colonization and cholera toxin acquisition. Here we report that TCP mediates
      bacterial interactions required for biofilm differentiation on chitinaceous
      surfaces. We also show that undifferentiated TCP- biofilms have reduced
      ecological fitness and, thus, that chitin colonization may represent an
      ecological setting outside the host in which selection for a host colonization
      factor may take place.

PMID- 15866945
TI  - Comparative analysis of differentially expressed genes in Shewanella oneidensis
      MR-1 following exposure to UVC, UVB, and UVA radiation.
AB  - We previously reported that Shewanella oneidensis MR-1 is highly sensitive to UVC
      (254 nm), UVB (290 to 320 nm), and UVA (320 to 400 nm). Here we delineated the
      cellular response of MR-1 to UV radiation damage by analyzing the transcriptional
      profile during a 1-h recovering period after UVC, UVB, and UVA exposure at a dose
      that yields about a 20% survival rate. Although the SOS response was observed
      with all three treatments, the induction was more robust in response to short
      wavelength UV radiation (UVB and UVC). Similarly, more prophage-related genes
      were induced by short-wavelength UV radiation. MR-1 showed an active
      detoxification mechanism in response to UVA, which included the induction of
      antioxidant enzymes and iron-sequestering proteins to scavenge reactive oxygen
      species. In addition, a great number of genes encoding multidrug and heavy metal
      efflux pumps were induced following UVA irradiation. Our data suggested that
      activation of prophages appears the major lethal factor in MR-1 following UVC or
      UVB irradiation, whereas oxidative damage contributes greatly to the high UVA
      sensitivity in MR-1.

PMID- 15866946
TI  - The Salmonella translocated effector SopA is targeted to the mitochondria of
      infected cells.
AB  - This study investigates the Salmonella effector protein SopA. We show that in
      Salmonella enterica serovar Dublin-infected cells, SopA(1-347) fused to two
      carboxy-terminal hemagglutinin tags partially colocalized with mitochondria.
      Transfection of eukaryotic cells with a panel of constructs encoding truncated
      versions of SopA identified that amino acids 100 to 347 were sufficient to target
      SopA to the mitochondria.

PMID- 15866947
TI  - Developmental-stage-specific assembly of ParB complexes in Streptomyces
      coelicolor hyphae.
AB  - In Streptomyces coelicolor ParB is required for accurate chromosome partitioning
      during sporulation. Using a functional ParB-enhanced green fluorescent protein
      fusion, we observed bright tip-associated foci and other weaker, irregular foci
      in S. coelicolor vegetative hyphae. In contrast, in aerial hyphae regularly
      spaced bright foci accompanied sporulation-associated chromosome condensation and
      septation.

PMID- 15866948
TI  - Purification and properties of the Klebsiella aerogenes UreE metal-binding
      domain, a functional metallochaperone of urease.
AB  - Klebsiella aerogenes UreE, a metallochaperone that delivers nickel ions during
      urease activation, consists of distinct "peptide-binding" and "metal-binding"
      domains and a His-rich C terminus. Deletion analyses revealed that the metal
      binding domain alone is sufficient to facilitate urease activation. This domain
      was purified and shown to exhibit metal-binding properties similar to those of
      UreE lacking only the His-rich tail.

PMID- 15866949
TI  - Bacteriophage Mu targets the trinucleotide sequence CGG.
AB  - Target specificity for bacteriophage Mu was studied using a new phage derivative
      that enabled cloning of Mu-host junctions from phage DNA. Insertions distributed
      throughout the chromosome showed no orientation bias with respect to
      transcription or replication polarity. Genes with a high frequency of the triplet
      CGG were preferred targets.

PMID- 15866950
TI  - Transcriptome analysis of the progressive adaptation of Lactococcus lactis to
      carbon starvation.
AB  - Adaptation of Lactococcus lactis towards progressive carbon starvation is
      mediated by three different types of transcriptomic responses: (i) global
      responses, i.e., general decreases of functions linked to bacterial growth and
      lack of induction of the general stress response; (ii) specific responses
      functionally related to glucose exhaustion, i.e., underexpression of central
      metabolism genes, induction of alternative sugar transport and metabolism, and
      induction of the arginine deiminase pathway; and (iii) other responses never
      described previously during carbon starvation.

PMID- 15866951
TI  - An adenylyl cyclase, CyaB, acts as an osmosensor in Myxococcus xanthus.
AB  - We have previously reported that a receptor-type adenylyl cyclase (CyaA) of
      Myxococcus xanthus undergoes an osmosensor mainly during spore germination (Y.
      Kimura et al., J. Bacteriol. 184:3578-3585, 2002). In the present study, we
      cloned another receptor-type adenylyl cyclase gene (cyaB) and characterized the
      function of the cyaB-encoded protein. Disruption of cyaB generates a mutant that
      showed growth retardation at high ionic (NaCl) or high nonionic (sucrose)
      osmolarity. When vegetative cells were stimulated with 0.15 M NaCl, the increases
      in intracellular cyclic AMP levels of cyaB mutant cells were lower than those of
      wild-type cells. Under nonionic osmostress, the cyaB mutant exhibited reduced
      spore germination; however, the germination rate of the cyaB mutant was
      significantly higher than that of the cyaA mutant.

PMID- 15866952
TI  - Localization of chaperones DnaK and GroEL in bacterial inclusion bodies.
AB  - By immunostaining and transmission electron microscopy, chaperones DnaK and GroEL
      have been identified at the solvent-exposed surface of bacterial inclusion bodies
      and entrapped within these aggregates, respectively. Functional implications of
      this distinct localization are discussed in the context of Escherichia coli
      protein quality control.

PMID- 15866953
TI  - Device for zone-II flexor tendon repair. A multicenter, randomized, blinded,
      clinical trial.
AB  - BACKGROUND: The stainless-steel Teno Fix tendon-repair device has improved
      biomechanical characteristics compared with those of suture repair, and it was
      well tolerated in a canine model. The purpose of this study was to compare the
      Teno Fix with suture repair in a clinical setting. METHODS: Sixty-seven patients
      with isolated zone-II flexor tendon injury were randomized to be treated with a
      Teno Fix or a four-stranded cruciate suture repair. There were eighty-five
      injured digits: thirty-four were treated with the Teno Fix, and fifty-one served
      as controls. A modified Kleinert rehabilitation technique was employed, with
      active flexion starting at four weeks postoperatively. Patients were followed for
      six months by blinded observers who determined the range of motion, Disabilities
      of the Arm, Shoulder and Hand (DASH) score, pinch and grip strength, and pain
      score on a verbal scale and assessed swelling and neurologic recovery. Adverse
      outcomes, including device migration and rupture, were monitored at frequent
      intervals. RESULTS: Nine of the fifty-one suture repairs ruptured, whereas none
      of the Teno Fix repairs ruptured (p < 0.01). Five of the nine ruptures were
      caused by resistive motion against medical advice. There were no differences
      between the two groups in terms of range of motion, DASH score, pinch and grip
      strength, pain, swelling, or neurologic recovery. The Teno Fix group had slightly
      slower resolution of pain and swelling compared with the control group. Of the
      patients who were available for follow-up at six months, sixteen of the twenty
      four treated with a Teno Fix repair and nineteen of the twenty-seven treated with
      a control repair had a good or excellent result. One Teno Fix device migrated and
      extruded secondary to a wound infection. Of all eighty-five digits that were
      operated on, four were thought to have tendons of inadequate size to accommodate
      the device and nine were deemed to have inadequate exposure to allow placement of
      the anchors. CONCLUSIONS: The Teno Fix is safe and effective for flexor tendon
      repair if the tendon size and exposure are sufficient. Tendon repairs with the
      Teno Fix have lower rupture rates and similar functional outcomes when compared
      with conventional repair, particularly in patients who are noncompliant with the
      rehabilitation protocol.

PMID- 15866954
TI  - Tissue-engineered osteochondral constructs in the shape of an articular condyle.
AB  - BACKGROUND: An entire articular condyle engineered from stem cells may provide an
      alternative therapeutic approach to total joint replacement. This study describes
      our continuing effort to optimize the chondrogenic and osteogenic differentiation
      from mesenchymal stem cells toward engineering articular condyles in vivo.
      METHODS: Primary rat bone-marrow mesenchymal stem cells were induced to
      differentiate into chondrogenic and osteogenic lineages in vitro and were
      suspended in polyethylene glycol-based hydrogel. The hydrogel cell suspensions,
      each at a density of 20 x 10(6) cells/mL, were stratified into two separate
      layers that were molded into the shape and dimensions of an adult human cadaveric
      mandibular condyle by sequential photopolymerization. The osteochondral
      constructs fabricated in vitro were implanted in the dorsum of immunodeficient
      mice for twelve weeks. RESULTS: De novo formation of articular condyles in the
      shape and dimensions of the adult human mandibular condyle occurred after a
      twelve-week period of in vivo implantation. Histological evaluation demonstrated
      two stratified layers of cartilaginous and osseous tissues, and yet there was
      mutual infiltration of cartilage-like and bone-like tissues into each other's
      territories. The cartilaginous portion was stained intensively to safranin O and
      expressed immunolocalized type-II collagen. Chondrocytes adjacent to the tissue
      engineered osteochondral junction were enlarged and expressed type-X collagen,
      typical of hypertrophic chondrocytes. The osseous portion contained bone
      trabeculae-like structures and expressed immunolocalized type-I collagen,
      osteopontin, and osteonectin. CONCLUSIONS: A cell encapsulation density of 20
      million cells/mL with in vivo incubation for twelve weeks yields further tissue
      maturation and phenotypic growth of both cartilage-like and bone-like tissues in
      the tissue-engineered articular condyle.

PMID- 15866955
TI  - Use of a distraction plate for distal radial fractures with metaphyseal and
      diaphyseal comminution.
AB  - BACKGROUND: Distal radial fractures with extensive comminution involving the
      metaphyseal-diaphyseal junction present a major treatment dilemma. Of particular
      difficulty are those fractures involving the articular surface. One approach is
      to apply a dorsal 3.5-mm plate extra-articularly from the radius to the third
      metacarpal, stabilizing the diaphysis and maintaining distraction across the
      radiocarpal joint. METHODS: Twenty-two patients treated with a distraction plate
      for a comminuted distal radial fracture were included in the study. With use of
      three limited incisions, a 3.5-mm ASIF plate was applied in distraction dorsally
      from the radial diaphysis, bypassing the comminuted segment, to the long-finger
      metacarpal, where it was fixed distally. The articular surface was anatomically
      reduced and was secured with Kirschner wires or screws. Eleven of the twenty-two
      fractures were treated with bone-grafting. The plate was removed after fracture
      consolidation (at an average of 124 days), and wrist motion was initiated. All
      patients were followed prospectively with use of radiographs, physical
      examination, and DASH (Disabilities of the Arm, Shoulder and Hand) scores.
      RESULTS: All fractures united by an average of 110 days. Radiographs showed an
      average palmar tilt of 4.6 degrees and an average ulnar variance of neutral (0
      degrees), whereas loss of radial length averaged 2 mm. Flexion and extension
      averaged 57 degrees and 65 degrees, respectively, and pronation and supination
      averaged 77 degrees and 76 degrees , respectively. The average DASH scores were
      34 points at six months, 15 points at one year, and 11.5 points at the time of
      final follow-up (at an average of 24.8 months). According to the Gartland-Werley
      rating system, fourteen patients had an excellent result, six had a good result,
      and two had a fair result. Grip strength and the range of motion of the wrist at
      one year correlated inversely with the proximal extent of fracture comminution
      into the diaphysis. The duration of plate immobilization did not correlate with
      the range of motion of the wrist or with the DASH score at one year. CONCLUSIONS:
      The use of a distraction plate combined with reduction of the articular surface
      and bone-grafting when needed can be an effective technique for treatment of
      fractures of the distal end of the radius with extensive metaphyseal and
      diaphyseal comminution. A functional range of motion with minimal disability can
      be achieved despite a prolonged period of fixation with a distraction plate
      across the wrist joint.

PMID- 15866956
TI  - Diagnostic accuracy of a new clinical test (the Thessaly test) for early
      detection of meniscal tears.
AB  - BACKGROUND: Clinical tests used for the detection of meniscal tears in the knee
      do not present acceptable diagnostic sensitivity and specificity values.
      Diagnostic accuracy is improved by arthroscopic evaluation or magnetic resonance
      imaging studies. The objective of this study was to evaluate the diagnostic
      accuracy of a new dynamic clinical examination test for the detection of meniscal
      tears. METHODS: Two hundred and thirteen symptomatic patients with knee injuries
      who were examined clinically, had magnetic resonance imaging studies performed,
      and underwent arthroscopic surgery and 197 asymptomatic volunteers who were
      examined clinically and had magnetic resonance imaging studies done of their
      normal knees were included in this study. For clinical examination, the medial
      and lateral joint-line tenderness test, the McMurray test, the Apley compression
      and distraction test, the Thessaly test at 5 degrees of knee flexion, and the
      Thessaly test at 20 degrees of knee flexion were used. For all clinical tests,
      the sensitivity, specificity, false-positive, false-negative, and diagnostic
      accuracy rates were calculated and compared with the arthroscopic and magnetic
      resonance imaging data for the test subjects and the magnetic resonance imaging
      data for the control population. RESULTS: The Thessaly test at 20 degrees of knee
      flexion had a high diagnostic accuracy rate of 94% in the detection of tears of
      the medial meniscus and 96% in the detection of tears of the lateral meniscus,
      and it had a low rate of false-positive and false-negative recordings. Other
      traditional clinical examination tests, with the exception of joint-line
      tenderness, which presented a diagnostic accuracy rate of 89% in the detection of
      lateral meniscal tears, showed inferior rates. CONCLUSIONS: The Thessaly test at
      20 degrees of knee flexion can be used effectively as a first-line clinical
      screening test for meniscal tears, reducing the need for and the cost of modern
      magnetic resonance imaging methods.

PMID- 15866957
TI  - Intermediate to long-term results of a treatment protocol for calcaneal fracture
      malunions.
AB  - BACKGROUND: Nonoperative management of displaced intra-articular calcaneal
      fractures may result in malunion affecting the function of both the ankle and the
      subtalar joint. The purpose of this study was to report the intermediate to long
      term results of a treatment protocol for calcaneal fracture malunions. METHODS:
      Seventy feet (sixty-four patients) with a malunion after nonoperative management
      of a displaced intra-articular calcaneal fracture were evaluated. On the basis of
      the classification system of Stephens and Sanders, type-I malunions were treated
      with a lateral wall exostectomy and peroneal tenolysis; type-II malunions, with a
      lateral wall exostectomy, peroneal tenolysis, and subtalar bone-block
      arthrodesis; and type-III malunions, with a lateral wall exostectomy, peroneal
      tenolysis, subtalar bone-block arthrodesis, and a calcaneal osteotomy. The
      patients were evaluated clinically and radiographically at a minimum of twenty
      four months following surgery. RESULTS: Forty-five feet in forty patients were
      available for follow-up evaluation at a minimum of two years, with an average
      duration of follow-up of 5.3 years. Thirty-seven (93%) of the forty feet that had
      an arthrodesis achieved union. Statistical analysis revealed no significant
      difference among the types of malunion with respect to the Maryland foot score,
      the American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot score,
      or the Short Form-36 (SF-36) health survey subscales, which was likely due to
      sample size discrepancies. Forty-two (93%) of the forty-five feet were aligned in
      neutral or slight valgus hindfoot alignment, and all forty-five were plantigrade.
      Twenty-nine (64%) of the forty-five feet had mild residual pain, and nineteen of
      them had pain in the lateral aspect of the ankle. Radiographically, talocalcaneal
      height was significantly greater for the type-III malunion group relative to the
      type-I and type-II malunion groups (p = 0.021). CONCLUSIONS: This treatment
      protocol proved to be effective in relieving pain, reestablishing a plantigrade
      foot, and improving patient function. Because of the difficulty we encountered in
      restoring the calcaneal height and the talocalcaneal relationship in this group
      of patients with a symptomatic calcaneal fracture malunion, we believe that
      patients with a displaced intra-articular calcaneal fracture may benefit from
      acute operative treatment.

PMID- 15866958
TI  - Interscalene regional anesthesia for shoulder surgery.
AB  - BACKGROUND: Despite a trend toward the use of regional anesthesia for orthopaedic
      procedures, there has been resistance to the use of interscalene regional block
      for shoulder surgery because of concerns about failed blocks and potential
      complications. METHODS: We retrospectively reviewed the cases of 568 consecutive
      patients who had shoulder surgery under interscalene regional block in a tertiary
      care, university-based practice with an anesthesiology residency program. The
      blocks were performed by a group of anesthesiologists who were dedicated to the
      concept of regional anesthesia in their practice. Complete anesthetic and
      orthopaedic records were available for 547 patients. The surgical procedure,
      planned type of anesthesia, occurrence of block failure, and the presence of
      complications were noted. RESULTS: Of the 547 patients, 295 underwent an
      arthroscopic procedure and 252 (including eighty who had an arthroplasty)
      underwent an open procedure. General anesthesia was the initial planned choice
      for sixty-nine patients because of the complexity or duration of the procedure,
      the anatomic location, or patient insistence. Thirty-four of the sixty-nine
      patients also received an interscalene regional block. Interscalene regional
      block alone was planned for 478 patients. A total of 462 patients (97%) had a
      successful block whereas sixteen required general anesthesia because the block
      was inadequate. The success of the block was independent of the type or length of
      the surgery. No patient had a seizure, pneumothorax, cardiac event, or other
      major complication. Twelve (2.3%) of the 512 patients who had a block had minor
      complications, which included sensory neuropathy in eleven patients and a complex
      regional pain syndrome that resolved at three months in one patient. For ten of
      the eleven patients, the neuropathy had resolved by six months. CONCLUSIONS:
      Interscalene regional block provides effective anesthesia for most types of
      shoulder surgery, including arthroplasty and fracture fixation. When administered
      by an anesthesiologist committed to and skilled in the technique, the block has
      an excellent rate of success and is associated with a relatively low complication
      rate.

PMID- 15866959
TI  - Efficacy of surgical preparation solutions in foot and ankle surgery.
AB  - BACKGROUND: Previous studies have demonstrated higher infection rates following
      orthopaedic procedures on the foot and ankle as compared with procedures
      involving other areas of the body. Previous studies also have documented the
      difficulty of eliminating bacteria from the forefoot prior to surgery. The
      purpose of the present study was to evaluate the efficacy of three different
      surgical skin-preparation solutions in eliminating potential bacterial pathogens
      from the foot. METHODS: A prospective study was undertaken to evaluate 125
      consecutive patients undergoing surgery of the foot and ankle. Each lower
      extremity was prepared with one of three randomly selected solutions: DuraPrep
      (0.7% iodine and 74% isopropyl alcohol), Techni-Care (3.0% chloroxylenol), or
      ChloraPrep (2% chlorhexidine gluconate and 70% isopropyl alcohol). After
      preparation, quantitative culture specimens were obtained from three locations:
      the hallux nailfold (the hallux site), the web spaces between the second and
      third and between the fourth and fifth digits (the toe site), and the anterior
      part of the tibia (the control site). RESULTS: In the Techni-Care group, bacteria
      grew on culture of specimens obtained from 95% of the hallux sites, 98% of the
      toe sites, and 35% of the control sites. In the DuraPrep group, bacteria grew on
      culture of specimens obtained from 65% of the hallux sites, 45% of the toe sites,
      and 23% of the control sites. In the ChloraPrep group, bacteria grew on culture
      of specimens from 30% of the hallux sites, 23% of the toe sites, and 10% of the
      control sites. ChloraPrep was the most effective agent for eliminating bacteria
      from the halluces and the toes (p < 0.0001). CONCLUSIONS: The use of effective
      preoperative preparation solution is an important step in limiting surgical wound
      contamination and preventing infection, particularly in foot and ankle surgery.
      Of the three solutions tested in the present study, the combination of
      chlorhexidine and alcohol (ChloraPrep) was most effective for eliminating
      bacteria from the forefoot prior to surgery.

PMID- 15866960
TI  - Preoperative skin preparation of the foot and ankle: bristles and alcohol are
      better.
AB  - BACKGROUND: The most efficient way to prepare the skin for foot and ankle surgery
      is unknown. In recent studies, >70% of aerobic bacterial cultures of specimens
      taken from the nail folds following skin preparation with povidone-iodine were
      positive. The goal of the current study was to determine the effect of isopropyl
      alcohol on the eradication of bacteria from the nails and skin of the normal foot
      and ankle. In addition, the effect of using a bristled brush rather than sponges
      to scrub the foot was investigated. METHODS: Four skin-preparation techniques
      were studied in two sets of twenty-five volunteers. In phase I of the study, the
      right foot and ankle of each member of the first set of volunteers was prepared
      with method 1, which consisted of a two-stage povidone-iodine scrub and paint
      with use of soft sponges. The left foot and ankle was prepared with method 2,
      which consisted of method 1 as well as an additional pre-wash with 70% isopropyl
      alcohol. In phase II, the right foot and ankle of each member of the second set
      of volunteers was prepared with method 3, which consisted of a povidone-iodine
      scrub and paint with use of a bristled brush to scrub the foot. The left side was
      prepared with method 4, which consisted of an alcohol scrub and paint with use of
      a bristled brush to scrub the foot. At the end of the preparation process,
      specimens for aerobic bacterial cultures were obtained from the hallucal nail
      fold, interdigital web spaces, and anterior aspect of the ankle. Cultures were
      interpreted as positive or negative, and the results were also assessed
      quantitatively. RESULTS: The rates of positive cultures of the nail-fold
      specimens were 76% and 80% after methods 1 and 2 (soft sponges) and 76% and 12%
      after methods 3 and 4 (bristled brush). The reduction in the percentage of
      positive cultures with method 4 was highly significant (p < 0.001). Cultures of
      the specimens from the web spaces showed a significant difference in the rates of
      positive results between methods 1 and 2 (36% and 8%, p < 0.05) but no
      significant difference between methods 3 and 4 (12% and 0%, p = 0.25). The rates
      of positive cultures of specimens from the anterior aspect of the ankle were
      consistently low (< or = 4% for all methods). Quantitative analysis of positive
      cultures demonstrated significant reductions (p < 0.01) in heavy growth when
      bristled brushes had been used, both with povidone-iodine and isopropyl alcohol.
      CONCLUSIONS: The use of isopropyl alcohol and the use of a bristled brush both
      have beneficial effects on the skin-preparation process before foot and ankle
      surgery. In the current investigation, the most effective technique was the use
      of isopropyl alcohol in conjunction with scrubbing with a bristled brush. Merely
      washing the foot with alcohol-soaked sponges provided limited benefit to the web
      spaces only.

PMID- 15866961
TI  - Long thoracic nerve: anatomy and functional assessment.
AB  - BACKGROUND: The anatomy and function of the long thoracic nerve are not fully
      understood. The purposes of this study were to clarify the anatomy of the long
      thoracic nerve and to propose a clinical test to assess the function of the upper
      division of the long thoracic nerve. METHODS: The long thoracic nerve and the
      serratus anterior muscle were studied in fifteen fresh cadavera. Six patients had
      an operation to treat a brachial plexus injury, and the long thoracic nerve was
      electrically stimulated. The resulting shoulder motion was then observed.
      RESULTS: The long thoracic nerve was formed by branches arising from the C5, C6,
      and C7 nerve roots. The C5 and C6 branches joined beneath the scalenus medius
      muscle to form the upper division of the long thoracic nerve, which was located 1
      cm posteriorly and superiorly to the upper trunk origin. The union of the upper
      division with the branch from C7 occurred caudally, in the axillary region. Two
      branches from the upper division of the long thoracic nerve to the upper portion
      of the serratus anterior muscle were consistently identified. After electrical
      stimulation of the upper division branches, shoulder protraction was observed.
      CONCLUSIONS AND CLINICAL RELEVANCE: In the supraclavicular region, the long
      thoracic nerve has a trajectory parallel to the brachial plexus, which is
      contrary to the schematic representation in most textbooks. The upper division of
      the long thoracic nerve can be assessed by the shoulder protraction test.

PMID- 15866962
TI  - Results of unicompartmental knee arthroplasty at a minimum of ten years of follow
      up.
AB  - BACKGROUND: There is a renewed interest in unicompartmental knee arthroplasty.
      The present report describes the minimum ten-year results associated with a
      unicompartmental knee arthroplasty design that is in current use. METHODS: Sixty
      two consecutive unicompartmental knee arthroplasties that were performed with
      cemented modular Miller-Galante implants in fifty-one patients were studied
      prospectively both clinically and radiographically. All patients had isolated
      unicompartmental disease without patellofemoral symptoms. No patient was lost to
      follow-up. Thirteen patients (thirteen knees) died after less than ten years of
      follow-up, leaving thirty-eight patients (forty-nine knees) with a minimum of ten
      years of follow-up. The average duration of follow-up was twelve years. RESULTS:
      The mean Hospital for Special Surgery knee score improved from 55 points
      preoperatively to 92 points at the time of the final follow-up. Thirty-nine knees
      (80%) had an excellent result, six (12%) had a good result, and four (8%) had a
      fair result. At the time of the final follow-up, thirty-nine knees (80%) had
      flexion to at least 120 degrees . Two patients (two knees) with well-fixed
      components underwent revision to total knee arthroplasty, at seven and eleven
      years, because of progression of patellofemoral arthritis. At the time of the
      final follow-up, no component was loose radiographically and there was no
      evidence of periprosthetic osteolysis. Radiographic evidence of progressive loss
      of joint space was observed in the opposite compartment of nine knees (18%) and
      in the patellofemoral space of seven knees (14%). Kaplan-Meier analysis revealed
      a survival rate of 98.0% +/- 2.0% at ten years and of 95.7% +/- 4.3% at thirteen
      years, with revision or radiographic loosening as the end point. The survival
      rate was 100% at thirteen years with aseptic loosening as the end point.
      CONCLUSIONS: After a minimum duration of follow-up of ten years, this cemented
      modular unicompartmental knee design was associated with excellent clinical and
      radiographic results. Although the ten-year survival rate was excellent,
      radiographic signs of progression of osteoarthritis in the other compartments
      continued at a slow rate. With appropriate indications and technique, this
      unicompartmental knee design can yield excellent results into the beginning of
      the second decade of use.

PMID- 15866963
TI  - Ilizarov hip reconstruction for the late sequelae of infantile hip infection.
AB  - BACKGROUND: The late sequelae of infantile hip infection include absence of the
      femoral head and neck, proximal migration of the femur, lower-extremity length
      discrepancy, abnormal gait, and pain. The Ilizarov hip reconstruction includes an
      acute valgus and extension osteotomy at the proximal part of the femur combined
      with gradual distraction for realignment and lengthening at a second, more
      distal, femoral osteotomy. The purpose of this study was to determine whether
      this technique can successfully treat the sequelae of infantile hip infection.
      METHODS: We performed a retrospective review of a series of eight consecutive
      patients with a Type-IV or V hip deformity, according to the classification
      system of Hunka et al., after an infantile hip infection. The patients' mean age
      at surgery was 11.2 years. All hips were unstable, with a mean of 3.8 cm of
      proximal migration. A mean valgus angulation of 44 degrees and a mean extension
      angulation of 19 degrees were created with the proximal osteotomies. Distal
      femoral lengthening averaged 5.7 cm, and distal femoral varus angular correction
      averaged 10 degrees. The mean time in the Ilizarov frame was 4.7 months. Outcomes
      were evaluated clinically and radiographically. The clinical evaluation included
      gait analysis and the use of a modified Harris hip score. RESULTS: At the time of
      follow-up, at a mean of five years, the mean lower-extremity length discrepancy
      had improved from 4.6 cm preoperatively to 0.7 cm. The mean modified Harris hip
      score had improved from 51 points to 73 points (p = 0.007). All extremities were
      well aligned, with a mean pelvic mechanical axis angle of 89 degrees. The mean
      deviation of the mechanical axis was 2 mm in a lateral direction. The mean stance
      time asymmetry improved from 16% to 5.4% (p = 0.0037), and the mean ground
      reaction force (second peak) improved from 102% of body weight to 122% of body
      weight (p = 0.0005). CONCLUSIONS: The Ilizarov hip reconstruction can
      successfully correct a Trendelenburg gait and simultaneously restore knee
      alignment and correct lower-extremity length discrepancy. When the procedure is
      performed on a young patient, remodeling of the proximal osteotomy site and
      development of lower-extremity length discrepancy should be expected and the
      procedure may need to be repeated.

PMID- 15866964
TI  - Surgical treatment of pigmented villonodular synovitis of the hip.
AB  - BACKGROUND: Pigmented villonodular synovitis of the hip is a rare disease.
      Synovectomy is generally accepted as the only surgical treatment for the
      disorder, but there have been few studies with a sufficient sample size and
      duration of follow-up to allow the evaluation of long-term outcomes. The aim of
      this study was to determine the long-term outcome of the treatment in sixteen
      patients. METHODS: Sixteen patients (nine men and seven women), with a mean age
      of 35.5 years at the time of surgery, were treated between 1970 and 1996.
      Complete synovectomy was performed in all patients; in addition, three had a cup
      arthroplasty, four had a total hip arthroplasty, and one had a monopolar
      arthroplasty. Clinical and radiographic outcomes were evaluated retrospectively
      at a mean of 16.7 years postoperatively. Only one patient was followed for less
      than eight years. RESULTS: Nine patients needed repeat surgery, but only one had
      recurrent synovitis, as detected with pathological examination fourteen years
      after treatment with synovectomy and cup arthroplasty. Secondary osteoarthritis
      developed in all eight patients who had been treated with synovectomy alone, and
      four of them required a total hip arthroplasty within the follow-up period.
      CONCLUSIONS: These results support earlier data indicating that osteoarthritis
      consistently develops in patients with pigmented villonodular synovitis of the
      hip. Complete synovectomy seems to be effective in preventing recurrence of the
      synovitis, but it does not appear to prevent the development of secondary
      osteoarthritis.

PMID- 15866965
TI  - Complications of fluoroscopically guided extraforaminal cervical nerve blocks. An
      analysis of 1036 injections.
AB  - BACKGROUND: A number of serious complications associated with fluoroscopically
      guided extraforaminal cervical nerve blocks have been reported in the literature.
      The purpose of the present study was to determine the rate of complications
      associated with these blocks and to determine whether needle positioning during
      the procedure affected the prevalence of complications at one institution.
      METHODS: Between October 1999 and June 2003, we performed 1036 fluoroscopically
      guided extraforaminal cervical nerve blocks in 844 patients. Plain radiographs
      documenting the procedure were made as part of the standard quality-assurance
      protocol. An independent observer who was uninvolved with the procedures reviewed
      a prospectively kept database on all patients. We subsequently reviewed the
      patient records to identify complications. RESULTS: There were no catastrophic
      complications such as vessel damage, paralysis, or death. Overall, fourteen
      patients (1.66%) had a minor complication in association with the procedure. With
      the numbers available, the rate of complications associated with pdeep injection
      (798 blocks) was not significantly different from that associated with shallow
      injection (238 blocks) (1.89% compared with 0.84%). However, the rate of
      complications associated with anterior placement of the needle tip (thirty-three
      blocks) was higher than that associated with ideal placement of the needle tip
      (904 blocks) (6.06% compared with 1.55%) (p = 0.04). CONCLUSIONS: No catastrophic
      complications occurred in this series of 1036 nerve blocks. We found that the
      medial-lateral needle depth as seen on frontal-view radiographs was not
      associated with complications, although the anterior positioning of the needle as
      seen on lateral-view radiographs was associated with minor complications. Our
      results suggest that, with our technique, cervical nerve blocks are relatively
      safe procedures.

PMID- 15866966
TI  - Impact of educational intervention on confidence and competence in the
      performance of a simple surgical task.
AB  - BACKGROUND: Many complex new procedures involve a learning curve, and patients
      treated by individuals who are new to a procedure may have more complications
      than those treated by a practitioner who has performed the intervention more
      frequently. Still, at some point on the learning curve, each individual must
      decide that he or she is qualified to perform a procedure, presumably on the
      basis of his or her level of confidence, background, education, and skill. To
      evaluate the interrelationship of these factors, we designed a study in which we
      assessed the performance of a simulated knee joint injection. METHODS: Ninety
      three practitioners attending a continuing medical education session on knee
      injection were randomized to receive skills instruction through the use of a
      printed manual, a video, or hands-on instruction; each performed one injection
      before and after instruction. The participants completed pre-instruction and post
      instruction questionnaires gauging confidence and also provided self-assessments
      of their performances of injections before and after instruction. Self
      assessments were compared with objective performance standards measured by custom
      designed knee models with electronic sensors that detected correct needle
      placement. RESULTS: Before instruction, the participants' confidence was
      significantly but inversely related to competent performance (r = -0.253, p =
      0.02); that is, greater confidence correlated with poorer performance. Both men
      and physician-practitioners displayed higher pre-instruction confidence (p <
      0.01), which was not correlated with better performance. After instruction,
      performance improved significantly in all three training groups (p < 0.001), with
      no significant differences in efficacy detected among the three groups (p =
      0.99). After instruction, confidence correlated with objective competence in all
      groups (r = 0.24, p = 0.04); however, this correlation was weaker than the
      correlation between the participants' confidence and their self-assessment of
      performance (r = 0.72, p = 0.001). CONCLUSIONS: Even low-intensity forms of
      instruction improve individuals' confidence, competence, and self-assessment of
      their skill in performing the fairly straightforward psychomotor task of
      simulated knee injection. However, men and physicians disproportionately
      overestimated their skills both before and after training, a finding that
      worsened as confidence increased. The inverse relationship between confidence and
      competence that we observed before the educational intervention as well as the
      demographic differences that we noted should raise questions about how complex
      new procedures should be introduced and when self-trained practitioners should
      begin to perform them.

PMID- 15866967
TI  - Development of the QuickDASH: comparison of three item-reduction approaches.
AB  - BACKGROUND: The purpose of this study was to develop a short, reliable, and valid
      measure of physical function and symptoms related to upper-limb musculoskeletal
      disorders by shortening the full, thirty-item DASH (Disabilities of the Arm,
      Shoulder and Hand) Outcome Measure. METHODS: Three item-reduction techniques were
      used on the cross-sectional field-testing data derived from a study of 407
      patients with various upper-limb conditions. These techniques were the concept
      retention method, the equidiscriminative item-total correlation, and the item
      response theory (Rasch modeling). Three eleven-item scales were created. Data
      from a longitudinal cohort study in which the DASH questionnaire was administered
      to 200 patients with shoulder and wrist/hand disorders were then used to assess
      the reliability (Cronbach alpha and test-retest reliability) and validity (cross
      sectional and longitudinal construct) of the three scales. Results were compared
      with those derived with the full DASH. RESULTS: The three versions were
      comparable with regard to their measurement properties. All had a Cronbach alpha
      of > or = 0.92 and an intraclass correlation coefficient of > or = 0.94. Evidence
      of construct validity was established (r > or = 0.64 with single-item indices of
      pain and function). The concept-retention method, the most subjective of the
      approaches to item reduction, ranked highest in terms of its similarity to the
      original DASH. CONCLUSIONS: The concept-retention version is named the QuickDASH.
      It contains eleven items and is similar with regard to scores and properties to
      the full DASH. A comparison of item-reduction approaches suggested that the
      retention of clinically sensible and important content produced a comparable, if
      not slightly better, instrument than did more statistically driven approaches.

PMID- 15866969
TI  - Function of skin grafts in children following acquired amputation of the lower
      extremity.
AB  - BACKGROUND: Investigators have recommended aggressive use of skin-grafting in
      order to preserve length and proximal joint function following an acquired
      amputation in children. However, there is little objective evidence to either
      support or refute that recommendation. METHODS: We performed a retrospective
      review of the cases of all children for whom a skin graft had been applied to the
      residual limb following an acquired lower-extremity amputation at our Limb
      Deficiency Clinic between 1984 and 2002. Skin graft dysfunction, defined as
      breakdown, contracture, and/or pain, was considered to be clinically relevant if
      it required the child to discontinue use of the prosthesis for any period of time
      or if it required revision surgery to facilitate continued prosthetic fitting.
      RESULTS: Twenty-three children (mean age at amputation, 4.4 years) with a total
      of thirty-one acquired lower-extremity amputations had been treated with skin
      grafting. At a mean of 6.3 years after the operation, sixteen (52%) of the thirty
      one extremities had had no episodes of skin graft dysfunction. The remaining
      fifteen extremities (48%) had had clinically relevant skin graft dysfunction
      (breakdown in thirteen and contracture and pain in one extremity each). Nine of
      the ten extensive skin grafts underwent clinically relevant breakdown, as did
      thirteen of the twenty-four grafts that were located distally on the residual
      limb. Subsequent surgical revision of the residual limb because of inadequate
      function of the skin graft was performed on seven extremities (23%), with
      revision to a more proximal limb-segment level required in five. CONCLUSIONS:
      Focal skin-grafting (involving < or = 25% of the surface area) of partial
      thickness soft-tissue defects in order to optimize the length of the residual
      limb at the time of an amputation is an effective option for children with an
      acquired lower-extremity amputation. Limited skin-grafting (involving 26% to 50%
      of the surface area) is more likely to result in skin graft breakdown,
      particularly when it is done distally. Extensive skin-grafting, while technically
      possible, frequently requires revision and rarely results in an optimally
      functioning limb. Alternative treatment strategies should be considered for
      extremities that would require extensive, distal skin-grafting.

PMID- 15866968
TI  - Early quadriceps strength loss after total knee arthroplasty. The contributions
      of muscle atrophy and failure of voluntary muscle activation.
AB  - BACKGROUND: While total knee arthroplasty reduces pain and provides a functional
      range of motion of the knee, quadriceps weakness and reduced functional capacity
      typically are still present one year after surgery. The purpose of the present
      investigation was to determine the role of failure of voluntary muscle activation
      and muscle atrophy in the early loss of quadriceps strength after surgery.
      METHODS: Twenty patients with unilateral knee osteoarthritis were tested an
      average of ten days before and twenty-seven days after primary total knee
      arthroplasty. Quadriceps strength and voluntary muscle activation were measured
      with use of a burst-superimposition technique in which a supramaximal burst of
      electrical stimulation is superimposed on a maximum voluntary isometric
      contraction. Maximal quadriceps cross-sectional area was assessed with use of
      magnetic resonance imaging. RESULTS: Postoperatively, quadriceps strength was
      decreased by 62%, voluntary activation was decreased by 17%, and maximal cross
      sectional area was decreased by 10% in comparison with the preoperative values;
      these differences were significant (p < 0.01). Collectively, failure of voluntary
      muscle activation and atrophy explained 85% of the loss of quadriceps strength (p
      < 0.001). Multiple linear regression analysis revealed that failure of voluntary
      activation contributed nearly twice as much as atrophy did to the loss of
      quadriceps strength. The severity of knee pain with muscle contraction did not
      change significantly compared with the preoperative level (p = 0.31). Changes in
      knee pain during strength-testing did not account for a significant amount of the
      change in voluntary activation (p = 0.14). CONCLUSIONS: Patients who are managed
      with total knee arthroplasty have profound impairment of quadriceps strength one
      month after surgery. This impairment is predominantly due to failure of voluntary
      muscle activation, and it is also influenced, to a lesser degree, by muscle
      atrophy. Knee pain with muscle contraction played a surprisingly small role in
      the reduction of muscle activation.

PMID- 15866970
TI  - Bone induction by AdBMP-2/collagen implants.
AB  - BACKGROUND: Demineralized bone matrix and recombinant human bone morphogenetic
      protein-2 or 7 (BMP-2 or BMP-7)-containing collagenous matrix have been shown to
      induce new bone formation in orthotopic and heterotopic sites. We examined the
      ability of subcutaneous implants of collagen combined with adenoviral vector
      containing the BMP-2 gene (AdBMP-2) to induce bone formation in rats. We also
      evaluated whether targeting the AdBMP-2 vector through an alternative receptor
      pathway, fibroblast growth factor (FGF), would increase the vector's potency.
      METHODS: In a time-course study, rat subcutaneous sites were implanted with (1)
      AdBMP-2 in rat-bone-derived collagen or (2) rat-bone-derived collagen alone.
      Samples were collected three, seven, fourteen, or thirty-five days after
      treatment. In a dose-response study, bone induction by AdBMP-2 in collagen (AdBMP
      2/collagen) or by AdBMP-2 and FGF2 Fab' anti-adenovirus knob protein antibody in
      collagen (FGF2-AdBMP-2/collagen) was tested at fourteen days. Viral vector doses
      of 1 x 10(9) PN (viral particle number), 3 x 10(9) PN, 1 x10(10) PN, 3 x 10(10)
      PN, or 1 x 10(11) PN per implant were used. Equal amounts of collagen (25 mg)
      were used to formulate all implants. Explanted tissues were evaluated
      histologically to determine bone formation, specific activity of alkaline
      phosphatase, and calcium content. RESULTS: AdBMP-2/collagen implants induced
      robust bone formation. New bone was formed by the fourteenth day after
      implantation. In contrast, little or no bone was induced by the implant
      containing collagen alone. FGF2-AdBMP-2/collagen implants stimulated
      significantly more bone formation (p < 0.05) than did AdBMP-2/collagen implants,
      regardless of the dose of viral particles. CONCLUSIONS: Local delivery of AdBMP-2
      in a collagen matrix rapidly induces bone formation, and targeting the virus
      through FGF receptors enhances the osteogenic potential of AdBMP-2.

PMID- 15866971
TI  - Decreased orthotic effectiveness in overweight patients with adolescent
      idiopathic scoliosis.
AB  - BACKGROUND: Many studies have demonstrated that orthotic treatment is effective
      for the prevention of curve progression in patients with adolescent idiopathic
      scoliosis. However, the effect of being overweight on the outcome of orthotic
      treatment has not been reported. The purpose of the present study was to
      determine whether orthotic treatment of adolescent idiopathic scoliosis is less
      successful for patients who are overweight than it is for those who are not
      overweight. METHODS: A ten-year multicenter retrospective review of patients in
      whom adolescent idiopathic scoliosis had been treated with a Boston or a custom
      molded thoracolumbosacral orthosis was performed. The inclusion criteria were no
      previous treatment, skeletal immaturity (a Risser sign of 0, 1, or 2), a curve of
      25 degrees to 40 degrees at the time of orthotic initiation, and follow-up to
      skeletal maturity. Patients were divided into two groups according to body
      habitus, with overweight patients defined as those with a body mass index in the
      eighty-fifth percentile or greater. Curve progression was compared between the
      two groups. Successful orthotic treatment was defined as no more than a 5 degrees
      increase in the primary curve from the start of orthotic wear to skeletal
      maturity. Absolute curve progression to 45 degrees or greater also was considered
      to be an adverse outcome. RESULTS: Two hundred and seventy-six consecutive
      patients from two institutions were analyzed, and thirty-one patients were
      considered to be overweight. The mean curve progression was 9.6 degrees +/- 7.3
      degrees for the patients who were overweight, compared with 3.6 degrees +/- 9.4
      degrees for those who were not overweight (p < 0.01). Overweight patients were
      3.1 times more likely to have an unsuccessful result than those who were not
      overweight. Curve progression to 45 degrees or greater occurred in fourteen (45%)
      of the thirty-one patients who were overweight, compared with sixty-nine (28%) of
      the 245 patients who were not overweight. CONCLUSIONS: The results of the present
      study suggest that overweight patients with adolescent idiopathic scoliosis will
      have greater curve progression and less successful results following orthotic
      treatment than those who are not overweight. The ability of an orthosis to
      transmit corrective forces to the spine through the ribs and soft tissue may be
      compromised in overweight patients. This factor should be taken into
      consideration when making treatment decisions. Additional study is warranted to
      determine a threshold effect.

PMID- 15866972
TI  - Revision of unstable capitellocondylar (unlinked) total elbow replacement.
AB  - BACKGROUND: Instability is a recognized complication associated with unlinked
      total elbow implants. The best form of treatment of this problem is uncertain as
      very little has been written about it. METHODS: Twelve patients underwent
      operative treatment of instability at the site of a capitellocondylar unlinked
      total elbow replacement, and the results were reviewed retrospectively. The study
      group included ten women and two men with an average age of fifty-eight years.
      Ten patients had rheumatoid arthritis. Three elbows underwent conversion to a
      semi-constrained hinged prosthesis. In the other nine elbows, an attempt was made
      to continue with an unlinked prosthesis: three had reconstruction of one or both
      collateral ligaments, four had component revision, and two had both ligament
      reconstruction and component revision. RESULTS: After an average duration of
      follow-up of six years (range, two to fifteen years) only three patients had
      retained a functioning unlinked prosthesis. Of the remaining nine patients, three
      had had a conversion to a semi-constrained arthroplasty at the time of the index
      procedure, four had had a conversion to a semi-constrained prosthesis at the time
      of a salvage procedure, one had had a resection arthroplasty, and one had a
      painfully dislocated elbow and had declined revision. Thus, seven elbows
      eventually underwent conversion to a semi-constrained prosthesis; these
      conversion procedures were technically difficult, with perforation of the humerus
      occurring in six patients and perforation of the ulna occurring in four. After
      all procedures, the average elbow flexion was 132 degrees and the average flexion
      contracture was 25 degrees. According to the Mayo Elbow Performance Index, there
      were four excellent results, three good results, three fair results, and one poor
      result. CONCLUSIONS: Revision of an unlinked total elbow prosthesis to a linked
      total elbow prosthesis is difficult, but it restores elbow function. Although the
      present series documents the unpredictability of attempts to salvage an unstable
      unlinked prosthesis, it seems reasonable to attempt at least one soft-tissue
      procedure before converting to a linked prosthesis.

PMID- 15866973
TI  - Polyethylene wear after total elbow arthroplasty.
AB  - BACKGROUND: Articular wear is considered to be a possible long-term complication
      of the use of stemmed, coupled elbow replacements with the capacity to correct
      deformity and restore function. There have been no reports on this topic, to our
      knowledge. METHODS: A review of the results of 919 replacements with the semi
      constrained linked Coonrad-Morrey total elbow implant, performed between 1981 and
      2000, revealed that twelve patients (1.3%) had undergone an isolated exchange of
      the articular bushings as a result of polyethylene wear. The status of these
      patients was assessed clinically and radiographically. RESULTS: The mean age of
      the twelve patients at the time of the initial total elbow replacement was forty
      four years compared with a mean age of sixty-two years in the overall group (p <
      0.001). Seven of the twelve patients had posttraumatic arthritis, and five had
      rheumatoid arthritis. Nine patients had extensive deformity. The group consisted
      of seven women and five men, and ten patients had involvement of the right
      dominant elbow. The mean age at the bushing revision was fifty-two years, and the
      bushings were revised at an average of 7.9 years after implantation. All twelve
      patients reported pain, and five reported crepitus or a squeaking sound. None had
      extensive osteolysis. The mean duration of follow-up after the bushing exchange
      was sixty-five months. The mean arc of motion improved from 89 degrees before the
      surgery to 109 degrees after it. Three of the twelve patients underwent an
      additional articular revision at fifty-three, fifty-four, and 136 months after
      the initial bushing exchange. At the time of final follow-up, all twelve patients
      had functioning elbows. CONCLUSIONS: Isolated bushing exchange can be a
      successful revision procedure in patients with a semi-constrained linked total
      elbow prosthesis. Younger patients with a posttraumatic condition and/or severe
      pre-existing deformity are at greater risk for the development of excessive
      bushing wear. Patients should be cautioned against exceeding the recommended
      activity and lifting restrictions.

PMID- 15866974
TI  - Human periprosthetic tissues implanted in severe combined immunodeficient mice
      respond to gene transfer of a cytokine inhibitor.
AB  - BACKGROUND: Periprosthetic tissue formation and local inflammation that are
      associated with wear debris contribute to the pathogenesis of aseptic loosening
      of a prosthesis. This study evaluated a retrovirus-mediated gene therapy with use
      of a novel xenograft-based animal model. METHODS: Human periprosthetic tissues
      obtained from patients during revision arthroplasty performed because of aseptic
      loosening of a prosthetic joint were transplanted into the left quadriceps and
      paravertebral muscles of severe combined immunodeficient (SCID) mice. The
      engrafted tissues were recovered seven, fifteen, or thirty days after
      implantation for histological and molecular analyses. The periprosthetic tissues
      were incubated with retroviruses encoding for human interleukin-1 receptor
      antagonist (hIL-1Ra) or bacteria beta-galactosidase (LacZ) at 37 degrees C for
      three hours prior to implantation to evaluate their responses to gene
      modification. RESULTS: The human periprosthetic tissues were well accepted in
      SCID mice for up to thirty days, with angiogenesis occurring in the majority of
      the implanted tissue sections. The histological appearance was consistent between
      the recovered graft tissue and the original donor tissue. Strong expression of
      interleukin-1, tumor necrosis factor, and interleukin-6 was detected in the
      xenografts with use of immunohistochemical stains. Histological analysis revealed
      that interleukin-1 receptor antagonist gene modification significantly decreased
      the total number of inflammatory cells (p < 0.01) in engrafted human tissue
      containing implant wear debris. Real-time reverse transcription-polymerase chain
      reaction and immunohistochemical staining showed declining expression levels of
      interleukin-1 and tumor necrosis factor following interleukin-1 receptor
      antagonist gene transfer in comparison with LacZ-transduced or virus-free
      controls. CONCLUSIONS: Human periprosthetic tissue can survive in the SCID mouse
      host for up to thirty days and responds to the interleukin-1 receptor antagonist
      gene transfer with the amelioration of inflammation.

PMID- 15866975
TI  - Traumatic spondylopelvic dissociation. A report of two cases.

PMID- 15866976
TI  - Treatment of U-shaped bone ankylosis of the knee with the Ilizarov method. A case
      report.

PMID- 15866977
TI  - Dislocation of rotating hinge knee prostheses. A report of four cases.

PMID- 15866978
TI  - Viscosupplementation pseudotumor. A case report.

PMID- 15866979
TI  - Posterolateral rotatory instability of the elbow in association with lateral
      epicondylitis. A report of three cases.

PMID- 15866980
TI  - Acute paraspinal compartment syndrome. A case report.

PMID- 15866981
TI  - Evidence-based review of the role of aprotinin in blood conservation during
      orthopaedic surgery.
AB  - Aprotinin is a serine protease inhibitor with antifibrinolytic properties that
      has been approved as a blood-conserving drug in cardiac surgery by the United
      States Food and Drug Administration. On the basis of the current evidence from
      Level-I trials, we make a grade-A recommendation for use of the high-dose
      aprotinin regimen in hip and spine surgery. Because of conflicting data, the low
      dose aprotinin therapy as well as the use of aprotinin in patients with cancer
      cannot be recommended (grade-I recommendation). High-quality randomized trials
      are necessary to determine the optimal (and minimal) therapeutic dose of
      aprotinin and the optimal time of aprotinin administration during surgery.

PMID- 15866982
TI  - Symposium: introducing technology into orthopaedic practice. How should it be
      done?

PMID- 15866983
TI  - The first orthopaedic researcher.

PMID- 15866984
TI  - Below-the-knee compared with above-the-knee amputation.

PMID- 15866985
TI  - Orientation of the femoral component in surface arthroplasty of the hip.

PMID- 15866986
TI  - Legg-Calve-Perthes disease: the effect of treatment on outcome.

PMID- 15866988
TI  - Stress test for predicting the need for surgical fixation of fibular fractures.

PMID- 15866990
TI  - Review: relocation and anterior release tests diagnose shoulder instability in
      selected patients.

PMID- 15866989
TI  - Injured limbs recover better with early mobilization and functional bracing than
      with cast immobilization.

PMID- 15866991
TI  - An internet-delivered cognitive-behavioral intervention with telephone support
      improved some coping skills in patients with chronic low back pain.

PMID- 15866992
TI  - What's new in pediatric orthopaedics.

PMID- 15866993
TI  - Raising children in an age of Ritalin.

PMID- 15866994
TI  - Andrology: pursuit of the scientific trinity.

PMID- 15866995
TI  - Complete asthenospermia: to diagnose or not to diagnose?

PMID- 15866996
TI  - Trainee page: Is time on your side?

PMID- 15866997
TI  - Tadalafil improved erectile function at twenty-four and thirty-six hours after
      dosing in men with erectile dysfunction: US trial.
AB  - In a previous study assessing tadalafil for the treatment of erectile dysfunction
      (ED), tadalafil 20 mg was shown to improve erectile function for up to 36 hours
      vs placebo. This study sought to demonstrate the effectiveness of both 10- and 20
      mg tadalafil vs placebo at 2 prespecified assigned times of 24 and 36 hours
      postdosing. This double-blind, placebo-controlled, parallel-group study
      randomized 483 men with ED into 6 groups according to a combination of treatment
      (placebo, tadalafil 10 or 20 mg) and assigned time (24 or 36 hours) for
      intercourse attempts. Patients were stratified by baseline ED severity based on
      Erectile Function Domain scores. The study had 4 phases: a 4-week run-in (no ED
      medication taken); a 2- to 4-week equilibration (dosing as needed); a 4- to 6
      week assessment; and a 6-month open-label extension. During the assessment phase,
      men took a total of 4 doses of study medication, each dose separated by more than
      or equal to 7 days. Efficacy was measured as the mean per-patient percentage of
      successful intercourse attempts (Sexual Encounter Profile Diary Question 3: SEP3)
      during the assessment phase. Men taking either 10- or 20-mg tadalafil had a
      significant increase in SEP3 from baseline scores vs placebo at both 24 hours (P
      = .038 and <.001 for 10 and 20 mg, respectively) and 36 hours (P < .001 for both
      doses) postdose. The mean per-patient percentages of successful intercourse
      attempts for the 24-hour time point were 41.8%, 55.8%, and 67.3% for placebo and
      tadalafil 10 and 20 mg, respectively; for the 36-hour time point, the mean per
      patient percentages were 32.8%, 56.2%, and 61.9% for placebo and tadalafil 10 and
      20 mg, respectively. The most common treatment-emergent adverse events were
      headache, back pain, dyspepsia, and nasopharyngitis. Both 10- and 20-mg tadalafil
      improved erectile function for up to 36 hours postdosing in men with ED of varied
      severity.

PMID- 15866998
TI  - Cloning and sequencing of cDNA encoding for the testis-specific fox (Vulpes
      vulpes) sperm polypeptide Vb of the cytochrome C oxidase.
AB  - Identification of fox (Vulpes vulpes) sperm antigens was carried out to assess
      their interest as a potential target for a contraceptive vaccine. We report here
      the cloning and sequencing of fSP8, a fox sperm protein of 14.7 kd. fSP8 was
      isoantigenic in foxes, as it was recognized by sera of both male and female foxes
      immunized with fox sperm proteins. No glycosylation was detected, on fSP8, as
      shown both by deglycosylation assay and lectin labeling. To determine the fSP8
      sequence, the NH2-terminal sequence was first obtained, and a piece of cDNA was
      amplified from testicular RNA by Rapid Amplification of cDNA extremities
      polymerase chain reaction. This piece was used to screen a cDNA library from fox
      testis by Southern blot. A sequence of 879 base pairs was obtained, which
      includes a major open reading frame coding for 128 amino acids. Mass
      spectrometric analyses have confirmed the position of the open reading frame.
      Analysis of the predicted amino acids sequence revealed no apparent transmembrane
      regions. Comparison of the protein sequence with the Prosite database
      demonstrated a homology with the Zinc binding site of the subunit Vb of the
      cytochrome c oxidase. On the C-terminal extremity, fSP8 presents a high homology
      to the Vb polypeptide of the cytochrome c oxidase from bovine, mouse, and human;
      however the 34 amino acids on the NH2-extremity were specific to fSP8. Moreover,
      it was demonstrated that this sequence was testis-specific. This could contribute
      to the antigenicity of this protein. fSP8 is one of the first fox sperm antigens
      to be cloned and sequenced.

PMID- 15866999
TI  - Treatment of varicocele: randomized prospective study on open surgery versus
      Tauber antegrade sclerotherapy.
AB  - The goal of this randomized prospective study in patients with varicocele was to
      evaluate the outcome following open surgery with inguinal approach versus
      antegrade sclerotherapy according to the Tauber procedure. From January 2002 to
      November 2003, we recruited 64 patients with left varicocele for this study. All
      patients were clinically examined, before surgery and again 8 months postsurgery,
      by objective examination, scrotal color Doppler ultrasound, and semen analysis.
      These patients were randomized in a balanced 4-block pattern: depending on
      randomization, the patients underwent open surgery (group A: 32 patients) or
      antegrade sclerotherapy according to the Tauber procedure (group B: 32 patients).
      At the current follow-up, it is possible to evaluate all the patients for whom we
      have preoperative and postoperative Doppler imaging and semen analysis. An
      analysis of seminal parameters shows a statistically significant improvement of
      the rate of fast progressive spermatozoa (P < .05) and reduction in immotile
      spermatozoa (P < .01) in those patients who underwent sclerotherapy compared to
      the patients who underwent open surgery. The outcomes of all other parameters
      (number and morphology) are fully comparable. Operating time is decidedly shorter
      for antegrade sclerotherapy (P < .01), but there are no significant differences
      in terms of early or late postoperative complications. It is widely known that
      varicocele is a condition found in 9% to 23% of the male population around the
      world; this percentage rises to 40% among infertile males. The treatment of this
      condition not only resolves clinical symptoms but also stops continuous damage to
      spermatogenesis, thereby potentially improving fertility. Our experience
      demonstrates that sclerotherapy (Tauber procedure) combines shorter surgical time
      and faster recovery of normal daily activities with significant improvement in
      sperm motility.

PMID- 15867000
TI  - Characterization and localization of cysteine-rich secretory protein 3 (CRISP-3)
      in the human male reproductive tract.
AB  - Mammalian members of the cysteine-rich secretory protein (CRISP) family are
      expressed predominantly in the male reproductive tract and are implicated in the
      process of reproduction from spermiogenesis, posttesticular sperm maturation, and
      capacitation to oocyte-sperm fusion, and possibly also penetration of the zona
      pellucida. Rodents express only 2 CRISPs (CRISP-1 and CRISP-2) in their male
      reproductive system, whereas humans and horses express an additional third member
      named CRISP-3. We have previously demonstrated that this protein is present in
      human seminal plasma as well as in other exocrine secretions, in blood plasma,
      and in neutrophilic granulocytes. To characterize the protein in seminal plasma
      and localize the production of CRISP-3 in the human male reproductive tract, we
      performed immunoblotting and enzyme-linked immunosorbent assay measurements of
      seminal plasma and immunohistochemistry and in situ hybridization of tissue
      specimens. We were able to show that human CRISP-3 is a quantitatively minor
      seminal plasma protein not associated with prostasomes. Furthermore, CRISP-3
      expression was found in the secretory epithelium throughout the male genital
      tract, with particularly high expression in the cauda epididymis and ampulla vas
      deferens. Examination of seminal plasma from vasectomized males indicates that
      organs downstream of the epididymis are probably the major sources of seminal
      plasma CRISP-3.

PMID- 15867001
TI  - Bioactivity of androgens within the testes and serum of normal men.
AB  - Little is known about how human spermatogenesis is regulated, so it is not
      surprising that there have been few breakthroughs in the treatment of male
      infertility resulting from abnormalities of spermatogenesis. Testosterone is the
      predominant intratesticular steroid in both the rat and man. Previous studies
      have shown that the testosterone concentration within the rat testis that is
      required for the quantitative maintenance of spermatogenesis is far higher than
      the total testosterone concentration in rat blood, indicating that much of the
      testosterone within the testis might be biologically inactive. In contrast to the
      rat, little is known about the androgen requirements for human spermatogenesis,
      in part because, until recently, a minimally invasive method suitable for
      obtaining intratesticular fluids from the human testis has not been available.
      Percutaneous aspiration now makes it feasible to do so. A major objective of the
      present study was to assay the bioactive androgen concentration within the testes
      of normal, fertile men. Percutaneous aspiration was used to obtain
      intratesticular fluid from such men, and we adapted a highly sensitive
      recombinant protein mammalian cell-based bioassay to measure androgen
      bioactivity. Total intratesticular testosterone concentration, which we define as
      immunoreactive testosterone as measured by radioimmunoassay, was well in excess
      of that in serum (1236 +/- 86 nM vs 11.7 +/- 0.7 nM). The concentration of
      bioactive androgens within the normal human testis was found to be about two
      thirds that of the total testosterone concentration. Interestingly, the
      concentration of the major, known binding proteins for testosterone within the
      testis, serum hormone-binding globulin (SHBG)/ABP (52.4 +/- 9.7 nM), was
      insufficient to account for the difference between total testosterone and
      bioactive androgens. This indicates that, in addition to its binding to SHBG/ABP,
      androgens may also be bound by unknown molecules, and that this contributes to
      reducing androgen bioactivity. These observations could have relevance for
      understanding the relationship between spermatogenesis and intratesticular
      androgens in normal men and in men diagnosed with infertility.

PMID- 15867002
TI  - Reduction of the incidence of sperm DNA fragmentation by oral antioxidant
      treatment.
AB  - Sperm DNA fragmentation is known to compromise male fertility. Previous findings
      have suggested the implication of oxidative stress in the etiology of this
      pathological condition. The present study was conducted to find out if the
      pathologically increased incidence of DNA fragmentation in ejaculated spermatozoa
      can be reduced by oral treatment with two antioxidants, vitamins C and E. Sixty
      four men with unexplained infertility and an elevated (> or = 15%) percentage of
      DNA-fragmented spermatozoa in the ejaculate were randomized between an
      antioxidant treatment (1 g vitamin C and 1 g vitamin E daily for 2 months) group
      and a placebo group. Sperm DNA fragmentation was evaluated by terminal
      deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assay before and
      after treatment. No differences in basic sperm parameters were found between the
      antioxidant treatment and the placebo group before or after treatment. However,
      the percentage of DNA-fragmented spermatozoa was markedly reduced (P < .001) in
      the antioxidant treatment group after the treatment (9.1 +/- 7.2) as compared
      with the pretreatment values (22.1 +/- 7.7). No difference in the pretreatment
      and posttreatment incidence of sperm DNA fragmentation was observed in the
      placebo group. These data show that sperm DNA damage can be efficiently treated
      with oral antioxidants administered during a relatively short time period.

PMID- 15867003
TI  - Strength measurement of the Sertoli-spermatid junctional complex.
AB  - The Sertoli cell ectoplasmic specialization (ES) is a specialized domain of the
      calcium-dependent Sertoli cell-spermatid junctional complex. Not only is it
      associated with the mechanical adhesion of the cells, but it also plays a role in
      the morphogenesis and differentiation of the developing germ cells. Abnormal or
      absent Sertoli ESs have been associated with step-8 spermatid sloughing and
      subsequent oligospermia. With a micropipette pressure transducing system (MPTS)
      to measure the force needed to detach germ cells from Sertoli cells, this study
      examined, for the first time, the strength of the junction between Sertoli cells
      and spermatids and between Sertoli cells and spermatocytes. The mean force needed
      to detach spermatocytes from Sertoli cells was 5.25 x 10(-7) pN, prestep-8
      spermatids from Sertoli cells was 4.73 x 10(-7) pN, step-8 spermatids from
      Sertoli cells was 8.82 x 10(-7) pN, and spermatids plus EDTA was 2.16 x 10(-7)
      pN. These data confirm the hypothesis that step-8 spermatids are more firmly
      attached to Sertoli cells than are spermatocytes and pre-step-8 spermatids and
      that calcium chelation reduces binding strength between Sertoli cells and
      spermatids. The MPTS is a useful tool in studying the various molecular models of
      the Sertoli-germ cell junctional strength and the role of reproductive hormones
      and enzymes in coupling and uncoupling of germ cells from Sertoli cells.

PMID- 15867004
TI  - Variability and laboratory factors affecting the sperm chromatin structure assay
      in human semen.
AB  - During the past decade, the sperm chromatin structure assay (SCSA) has become an
      important tool for assessing semen quality in the human andrology laboratory. The
      SCSA uses the metachromatic properties of the fluorescent dye acridine orange
      (AO) in combination with flow cytometry to determine the sperm DNA susceptibility
      to denaturation in situ. The objective of this study was to evaluate laboratory
      factors affecting the SCSA and the variation between replicates. Semen ejaculates
      from 3 healthy volunteers were analyzed using the SCSA protocol as described by
      Evenson and Jost (2000), determining the X-mean, Y-mean, DNA fragmentation index
      (DFI), standard deviation of DFI (SD-DFI), and high DNA stainability (HDS). In
      experiment 1, the effects of thawing time, time of day, day, laboratory
      technician, donor, and incubation period before analysis were investigated. In
      experiment 2, the effects of sheath fluid, AO equilibration buffer, day,
      laboratory technician, donor, and incubation period before analysis were
      investigated. A significant difference was found between the 3 donors with
      respect to the X-mean, Y-mean, DFI, SD-DFI, and HDS. It was shown that incubation
      of the semen samples on ice postthaw had a significant effect on the X-mean, Y
      mean, DFI, and SD-DFI. The laboratory technician conducting the analysis
      accounted for up to 15.4% for the variation of the SCSA measurements. The time of
      day affected the variation for the Y-mean (23.5% of the total variation of the Y
      mean), and the day affected the variation for the X-mean (82.8% of the total
      variation of the X-mean). Incubation on ice for 5 to 25 minutes postthaw had a
      significant effect on the DFI and SD-DFI in both experiments. This study shows
      that several protocol steps in the SCSA affect the results obtained from the
      assay. Precise protocol description and standardization of the SCSA are therefore
      essential to achieve high agreement within and between different laboratories.

PMID- 15867005
TI  - Paracrine modulation of androgen synthesis in rat leydig cells by nitric oxide.
AB  - The free radical nitric oxide (NO), generated through the oxidation of L-arginine
      to L-citrulline by NO synthases (NOSs), has been shown to inhibit steroidogenic
      pathways. NOS isoforms are known to be present in rat and human testes. Our study
      examined the sensitivity of Leydig cells to NO and determined whether NOS
      activity resides in Leydig cells or in another cell type such as the testicular
      macrophage. The results showed a low level of L-[14C]arginine conversion in
      purified rat Leydig cell homogenates. Administration of the NOS inhibitor L-N(G)
      nitro-arginine methyl ester (L-NAME), or the calcium chelator ethylenebis
      (oxyethylenenitrilo)tetraacetic acid (EGTA), had no effect on L-[14C]citrulline
      accumulation. Increased intracellular Ca2+ concentrations that were induced by a
      calcium ionophore, or the addition of luteinizing hormone (LH), failed to affect
      NO formation in intact cells that were cultured in vitro. Introduction of a high
      concentration of the NO precursor L-arginine did not decrease testosterone (T)
      production, and NOS inhibitors did not increase T biosynthesis. However, exposing
      Leydig cells to low concentrations of the NO donor S-nitrosoglutathione (GSNO)
      induced a dramatic blockade of T production under basal and LH-stimulated
      conditions. DNA array assays showed a low level of expression of endothelial NOS
      (eNOS), while the neuronal and inducible isoforms of NOS (nNOS and iNOS) were
      below detection levels. Reverse transcriptase-polymerase chain reaction (RT-PCR)
      analyses confirmed these findings and demonstrated the presence of high iNOS
      messenger RNA (mRNA) levels in activated testicular macrophages that produced
      large amounts of NO. These data suggest that, while T production in rat Leydig
      cells is highly sensitive to NO and an endogenous NO-generating system is not
      present in these cells, NOS activity is more likely to reside in activated
      testicular macrophages.

PMID- 15867006
TI  - Regulatory cytokine expression and interstitial fluid formation in the normal and
      inflamed rat testis are under leydig cell control.
AB  - Leydig cells have been implicated in several inflammation-related responses of
      the testis. Specifically, these cells produce the proinflammatory cytokines
      interleukin-1 (IL-1) and IL-6, stimulate macrophage recruitment, and promote
      interstitial fluid formation. In addition, the immunoregulatory cytokines
      macrophage migration inhibitory factor (MIF), transforming growth factor-beta1
      (TGFbeta1), and interferon-gamma (IFNgamma) are constitutively expressed by
      testicular cells, including the Leydig cells. In the present study, the
      contribution of the Leydig cell to testicular inflammatory responses was examined
      in adult male rats treated with the Leydig cell-specific toxin, ethane dimethane
      sulfonate (EDS). Intratesticular testosterone levels were modulated by
      subcutaneous testosterone implants. After 10 days, animals received an injection
      of lipopolysaccharide (LPS) to induce an inflammatory response, or saline alone,
      and were killed 3 hours later. Both depletion of Leydig cells by EDS and LPS
      treatment caused a decrease in collected testicular interstitial fluid to about
      35% of control levels, but the effects were not additive. Maintenance of
      intratesticular testosterone reversed the interstitial fluid decline following
      EDS treatment and partially prevented the LPS-induced effect. MIF, TGFbeta1, and
      IFNgamma were expressed in both the normal and inflamed testis at similar levels.
      In contrast, EDS treatment caused a significant decline in expression of all 3
      cytokines, which was prevented by the testosterone implants. These data indicate
      that 1) expression of TGFbeta1, MIF, and IFNgamma in the testis is not dependent
      on the presence of intact Leydig cells but is under direct testosterone control
      and 2) the decline in testicular interstitial fluid during inflammation involves
      the Leydig cells, acting via both androgens and nonandrogenic secretions. These
      data provide further support for a significant role for the Leydig cell in
      modulating the testicular response to inflammation.

PMID- 15867007
TI  - Effects of various extenders and permeating cryoprotectants on cryopreservation
      of cynomolgus monkey (Macaca fascicularis) spermatozoa.
AB  - The cryoprotective effects of 11 different extenders, TTE, DM, mDM, LG-DM, G-DM,
      TCG, TEST, TSM, Test-M, Test-H, and LM, on sperm cryopreservation of cynomolgus
      monkey (Macaca fascicularis) have been compared with glycerol as cryoprotectant.
      Sperm motility, plasma membrane, and acrosomal integrity were examined to
      evaluate frozen-thawed sperm function. The results showed that TTE, DM, mDM, LG
      DM, G-DM, and TCG exhibited the best and similar protective efficiencies for
      cynomolgus monkey sperm cryopreservation in terms of sperm motility and plasma
      membrane integrity (P > .05). The acrosomal integrity for spermatozoa
      cryopreserved in TCG was statistically lower than that of TTE, DM, mDM, LG-DM,
      and G-DM (P < .05) but was significantly higher than that of TEST, TSM, Test-M,
      Test-H, and LM (P < .05). The postthaw sperm motility for 5 other extenders
      (TEST, TSM, Test-M, Test-H, and LM) did not exceed 30%, and the 3 sperm
      parameters evaluated for them were significantly lower than that of TTE, DM, mDM,
      LG-DM, G-DM, and TCG (P < .05). On the basis of these findings, 5 commonly used
      permeating cryoprotectants, glycerol, ethylene glycol, dimethyl sulfoxide,
      acetamide and propylene glycol have further been tested for their effectiveness
      on sperm cryopreservation in extenders of TTE, DM, mDM, LG-DM, G-DM, and TCG. The
      results showed that the sperm cryoprotective efficiencies of glycerol and
      ethylene glycol were similar and best among 5 permeating cryoprotectant
      treatments (P > .05). Dimethyl sulfoxide or acetamide resulted in average
      cryoprotection for cynomolgus monkey spermatozoa: poorer than glycerol or
      ethylene glycol but better than that of propylene glycol (P < .05). In addition,
      the action of permeating cryoprotectant appeared to be independent of extenders.
      The results in the present study demonstrate that 1) TTE, DM, mDM, LG-DM, G-DM,
      and TCG are excellent extenders and suitable for cynomolgus monkey sperm
      cryopreservation; 2) the mechanism of action of permeating cryoprotectants are
      not affected by extender composition; 3) ethylene glycol has a similar
      cryoprotective efficacy to glycerol that makes it a successful cryoprotectant for
      sperm cryopreservation in cynomolgus monkeys.

PMID- 15867008
TI  - Cooling and freezing of boar spermatozoa: supplementation of the freezing media
      with reduced glutathione preserves sperm function.
AB  - In this study, we evaluated the effects of glutathione (L-gamma-glutamyl-L
      cysteinylglycine; GSH) supplementation of the freezing extender on semen
      parameters during the cooling (2 hours at 5 degrees C) and freezing phases of the
      cryopreservation process to compensate for the decrease in GSH content observed
      during sperm freezing. To fully address these questions, we incorporated a new
      set of functional sperm tests. These included tests of mitochondrial function,
      inducibility of the acrosome reaction, in vitro penetration (IVP) of oocytes,
      changes in sulfhydryl group content in membrane proteins, and capacitation
      status. The main findings emerging from this study were that the addition of GSH
      to the freezing media resulted in 1) an improvement in percent motility (%MOT)
      and motion parameters of thawed spermatozoa, as measured by both microscopic
      analysis and computer-assisted semen analysis (CASA); 2) a higher number of total
      viable spermatozoa; 3) a higher number of noncapacitated viable spermatozoa; and
      4) a decrease in the number of spermatozoa with changes in the sulfhydryl groups
      in membrane proteins. This protective effect on sperm function was more
      pronounced with 1 mM of GSH than with 5 mM of GSH.

PMID- 15867009
TI  - Intramuscular testosterone enanthate plus very low dosage oral levonorgestrel
      suppresses spermatogenesis without causing weight gain in normal young men: a
      randomized clinical trial.
AB  - The development of a safe, well-tolerated, effective, and reversible male
      hormonal contraceptive would be a major clinical advance for couples planning
      their family size and for control of population growth. High-dosage parenteral
      testosterone (T) esters alone or in combination with a progestogen (eg, depot
      medroxyprogesterone) have been shown to confer effective and reversible male
      contraception in clinical trials, but these regimens are associated with weight
      gain and suppression of serum high-density lipoprotein cholesterol (HDL) levels.
      We have previously demonstrated that intramuscular T enanthate 100 mg weekly plus
      oral levonorgestrel (LNG) 125, 250, or 500 microg daily suppresses
      spermatogenesis to levels associated with effective contraception, but there is a
      LNG-dosage-dependent effect of weight gain and HDL suppression. We hypothesized
      that intramuscular T enanthate 100 mg weekly plus a very low dosage of oral LNG
      would effectively suppress spermatogenesis in normal men without inducing weight
      gain or HDL suppression. We conducted a randomized trial comparing 6 months of
      intramuscular T enanthate (100 mg weekly) plus 31.25 microg of oral LNG daily
      (T+LNG 31; n = 20) or 62.5 microg of oral LNG daily (T+LNG 62; n = 21). The 2
      regimens were equally effective in suppressing spermatogenesis to azoospermia,
      fewer than 1 million sperm/mL and fewer than 3 million sperm/mL (T+LNG 31 [60%,
      85%, and 90%] vs T+LNG 62 [62%, 91%, and 95%] for azoospermia, fewer than 1
      million and fewer than 3 million, respectively; P = NS). The T+LNG 31 group did
      not gain weight (0.25 +/- 1.08 kg; P = NS compared with baseline), but the T+LNG
      62 group gained 2.5 +/- 0.77 kg (P < .05 compared with baseline). Serum HDL
      cholesterol levels declined significantly in both groups (percentage decline
      month 6 of treatment vs baseline: 12.0% +/- 2.6% and 15.1% +/- 3.0%; P < .05 for
      T+LNG 31 and 62 respectively). Serum low-density lipoprotein cholesterol levels
      also declined in both groups (percentage decline month 6 of treatment vs
      baseline: 6.9 +/- 3.9 and 6.0% +/- 4.1%; P < .05 for T+LNG 31 and P = NS for
      T+LNG 62). There were no clinically significant adverse events or significant
      changes in hematology or chemistry profiles in either group during the study. We
      conclude that 1) intramuscular T plus oral LNG has a very potent synergistic
      effect in suppressing spermatogenesis at LNG dosages equal to or lower than
      dosages used in common female oral contraceptive regimens and 2) large, long-term
      contraceptive efficacy trials should be conducted with a variety of androgen
      progestogen combinations including long-acting T formulations such as depot T
      pellets or intramuscular T undecanoate plus depot LNG or very low dosage oral
      LNG.

PMID- 15867010
TI  - Biological activity assessment of a novel contraceptive antimicrobial agent.
AB  - Microbicides are a new category of compounds being developed as a prophylactic
      approach for the prevention of transmission of sexually transmitted diseases
      (STDs), including the human immunodeficiency virus (HIV). These are primarily
      being developed as women-controlled methods, with the target of designing new
      compounds or formulations that can be used without the knowledge of a male
      partner. Microbicide screening can be initially based on their hyaluronidase
      inhibiting (HI) activity, as this enzyme plays a major role in the sperm and
      microbe penetration into the substrate. Derivatives of hesperidin, a citrus
      flavonoid glycoside, have been reported in the literature for their HI effects.
      Hesperidin was thereby sulphonated under strictly controlled conditions and the
      active fraction isolated and characterized, based on its HI activity. This
      derivative was screened for antimicrobial and enzyme-inhibitory activities,
      specifically for the reproductive tract. Sulphonated hesperidin (SH) was found to
      completely inhibit the sperm enzymes hyaluronidase, giving an indication toward
      its contraceptive effects. It was also been found to inhibit various sexually
      transmitted pathogens, including Chlamydia trachomatis, Neisseria gonorrhoea,
      HIV, and Herpes Simplex virus type 2 (HSV-2). Its safety assessment was based on
      its noninterference in sperm motility and its penetration through the cervical
      mucus, and no effect on the growth of lactobacilli, the normal vaginal flora. It
      was also found to be nontoxic to the HIV substrate cells (MT2 cells). The study
      concludes that sulphonated hesperidin can be developed as a potential microbicide
      for a dual prophylaxis of contraception and transmission of STDs and AIDS.

PMID- 15867011
TI  - Cell growth effects of triiodothyronine and expression of thyroid hormone
      receptor in prostate carcinoma cells.
AB  - Thiiodothyronine (T3) plays an important role in the regulation of cell growth
      and differentiation. In this study, we show the different effects of T3 on cell
      growth response and expression of the thyroid hormone receptor in human prostate
      cell lines from normal to hormonal refractory metastatic cancer cells. Although
      the thyroid hormone receptor (TRbeta1) ubiquitously express in human prostatic
      epithelium cell lines (PZ-HPV-7, CA-HPV-10, LNCaP, DU145, PC-3), T3 did not show
      any effect on the cell proliferation of prostatic cell lines except LNCaP cells
      in vitro. Immunoblot assay revealed that PZ-HPV-7 and CA-HPV-10 cells express 5
      10-fold of TRbeta1 more than LNCaP cells; however, the immunocytochemical
      staining and immunoblot assay of cellular fractions suggested the TRbeta1 is
      located on the cell nuclear membrane of PZ-HPV-7 and CA-HPV-10 cells. Our results
      suggested that T3 upregulates cellular proliferation on LNCaP cells but not other
      prostatic carcinoma cells and PZ-HPV-7 and CA-HPV-10 cells express the novel
      TRbeta1, which locates at cell nuclear membrane.

PMID- 15867012
TI  - Idiopathic infertility: effect of palmitoylethanolamide (a homologue of
      anandamide) on hyperactivated sperm cell motility and Ca2+ influx.
AB  - The goal of this study was to examine the effect of palmitoylethanolamide (PEA)
      on the capacitation process and hyperactivated motility (HA) in idiopathic
      infertile men. Our data show the effect of PEA on the kinematic parameters of
      sperm cells from idiopathic infertile men during the capacitation of spermatozoa
      in vitro, both in the presence and absence of 2.5 nM PEA, a molecule
      physiologically present in human reproductive tracts. Two groups of sperm cells
      were identified. In group I (36 +/- 14 x 10(6) cells/mL), PEA significantly
      increased some motility parameters and HA during capacitation. In group II (58 +/
      18 x 10(6) cells/mL), PEA did not significantly modify motility parameters and
      HA. Fura 2 AM (acetoxymethyl ester derivative of fura 2) measurements
      demonstrated that PEA increased external Ca2+ influx (which modulates HA) in
      group I, while no change was measured in group II. In conclusion, our data
      indicated that PEA modulated certain physiological sperm functions that are
      involved in fertilization; in particular, we showed that PEA modulated for HA in
      men with low sperm kinematic parameters.

PMID- 15867013
TI  - Transient psychosis in an immune-competent patient after oral trimethoprim
      sulfamethoxazole administration.
AB  - We describe a rare adverse reaction to trimethoprim-sulfamethoxazole (TMP-SMX;
      Septra, Bactrim) in an immune-competent female adolescent. She was prescribed TMP
      SMX for a urinary tract infection, which she had developed while being treated in
      the hospital for an extensive leg cellulitis. Shortly after receiving her third
      dose of TMP-SMX, she developed an acute altered mental status with agitation as
      well as vivid visual and auditory hallucinations. After prompt discontinuation of
      TMP-SMX, the patient slowly began to improve and was able to return to her
      baseline mental status within 10 days. No residual mental status changes were
      present. Despite the recent emergence of multidrug-resistant bacterial pathogens,
      TMP-SMX, one of the first-generation broad-spectrum antibiotics, continues to be
      widely prescribed, in part because of its low cost and its easy availability. It
      is generally well tolerated and is associated with relatively few adverse
      effects. More common toxicities associated with TMP-SMX include hypersensitivity
      reactions, bone marrow suppression, and gastrointestinal side effects. Central
      nervous system toxicity is very rare; when reported, it has been in an immune
      compromised or an elderly patient.

PMID- 15867014
TI  - Procalcitonin as a predictor of vesicoureteral reflux in children with a first
      febrile urinary tract infection.
AB  - OBJECTIVE: A first febrile urinary tract infection leads to the diagnosis of
      vesicoureteral reflux in 20% to 40% of children. Systematic voiding
      cystourethrography then is recommended. However, for 60% to 80% of the children,
      voiding cystourethrography is a posteriori normal. Moreover, it is irradiating,
      painful, and expensive. Thus, selective approaches are needed. Because
      procalcitonin has been shown to be associated with severe pyelonephritis and
      renal scars, which are correlated to vesicoureteral reflux, we analyzed its
      relationship with vesicoureteral reflux. METHODS: A retrospective hospital-based
      cohort study included all children who were 1 month to 4 years of age and had a
      first febrile urinary tract infection. Univariate and multivariate analyses were
      performed. RESULTS: Among 136 patients included, 25% had vesicoureteral reflux.
      The median procalcitonin concentration was significantly higher in children with
      reflux than in those without (1.2 vs 0.6 ng/mL). High procalcitonin (> or =0.5
      ng/mL) was associated with reflux (odds ratio [OR]: 4.6; 95% confidence interval
      [CI]: 1.6-16.2). After logistic-regression adjustment for all potential
      confounders, the association remained significant (OR: 4.9; 95% CI: 1.7-14.0).
      The relationship was stronger for high-grade (> or =3) reflux (OR: 8.7; 95% CI:
      1.2-382) than low-grade reflux (OR: 3.6; 95% CI: 1.1-15.3). High procalcitonin
      sensitivities were 85% (95% CI: 70-94) and 92% (95% CI: 65-99) for all-grade and
      high-grade reflux, respectively, with 44% specificity (95% CI: 35-54).
      CONCLUSION: High procalcitonin is a strong and independent predictor of
      vesicoureteral reflux and could be used to identify low-risk patients to avoid
      unnecessary voiding cystourethrography.

PMID- 15867015
TI  - What caused the epidemic of Pneumocystis pneumonia in European premature infants
      in the mid-20th century?
AB  - An epidemic of interstitial pneumonia principally involving premature infants
      occurred in Germany and nearby European countries between the 1920s and 1960s.
      Fatalities were due to Pneumocystis. Because the principal defenses against
      Pneumocystis are T cells, an acquired T-cell deficiency was postulated. A number
      of potential causes including malnutrition were considered. All were implausible
      except for a retrovirus that was benign in adults but virulent in premature
      infants. Furthermore, we suspect that the virus was imported into Germany from
      former German African colonies. Premature infants were vulnerable because of the
      developmental status of their T cells. Given the practices in that part of Europe
      at that time, the virus was most likely transmitted by contaminated blood
      transfusions and subsequent contamination of reusable needles and syringes used
      in injections. Although the epidemic ended 4 decades ago, a search for the
      postulated retrovirus can be conducted if tissues from affected infants are
      available.

PMID- 15867016
TI  - An evaluation of the Motion Picture Association of America's treatment of
      violence in PG-, PG-13-, and R-rated films.
AB  - OBJECTIVE: The purpose of this study was to determine whether the Motion Picture
      Association of America's ratings system distinguishes among the 3 primary rating
      categories (PG, PG-13, and R) with respect to violence based on a study of the
      100 top-grossing films of 1994. METHODS: The Motion Picture Association of
      America assigns age-based ratings for every film that is released in the United
      States accompanied by the reasons for the rating. A data abstraction instrument
      was designed to code each act of violence within the sample of 100 films. A
      series of Poisson regression models were used to examine the association among
      rating, seriousness of violence, and primary reason for the rating assignment.
      RESULTS: The total average number of violent acts within each film by rating
      category increased from PG (14) to PG-13 (20) to R (32). However, using results
      from the Poisson models, it is clear that the rating does not predict the
      frequency of violence in films. For all 3 rating categories, the predicted number
      of violent acts is almost identical for films with violence as a primary
      descriptor and films with the highest level of seriousness (R = 62.4 acts, PG-13
      = 55.2 acts, and PG = 56.1 acts). The regression analysis shows that the rating
      does not predict the frequency of violence that occurs in films. CONCLUSIONS:
      Frequency of violence alone is not the most important criterion for the
      assignment of rating. The content descriptors and average seriousness of films
      are better measures of the violence than rating assignment.

PMID- 15867017
TI  - CHIP shots: association between the State Children's Health Insurance Programs
      and immunization rates.
AB  - OBJECTIVE: The Balanced Budget Act of 1997 established the State Children's
      Health Insurance Program (SCHIP), which makes health insurance available to
      children in near-poor families who are ineligible for Medicaid. SCHIP mandates
      that all state plans cover the cost and administration of childhood vaccines.
      Whether SCHIP has narrowed immunization coverage rates between near-poor and
      nonpoor children is unknown. The objective of this study was to use data from the
      National Immunization Survey from 1995 to 2002 to analyze changes in immunization
      coverage rates among poor, near-poor, and nonpoor children before and after
      implementation of SCHIP. METHODS: A prepost analysis was made of changes in
      immunization rates among poor, near-poor, and nonpoor children before and after
      implementation of SCHIP in all 50 states and 28 Immunization Action Plan areas
      from 1995 to 2002. All children in the National Immunization Survey for whom
      information on vaccinations was available from the respondents' shot cards and/or
      from the children's immunization providers (N = 264214) were studied. Up-to-date
      status for the 4:3:1 (4 doses of diphtheria-tetanus toxoids-pertussis vaccine/3
      doses of poliovirus vaccine/1 dose of measles-mumps-rubella vaccine) and the
      4:3:1:3:3 (4 doses of diphtheria-tetanus toxoids-pertussis vaccine/3 doses of
      poliovirus vaccine/1 dose of measles-mumps-rubella vaccine/3 doses of Haemophilus
      influenzae type B vaccine/3 doses of hepatitis B vaccine) series as well at the
      hepatitis B and varicella vaccines was measured. RESULTS: The probability that a
      poor or near-poor child was up to date for the 4:3:1:3:3 vaccine series increased
      approximately 11 percentage points after implementation of SCHIP. However, we
      observed a similar increase for nonpoor children. The proportion of poor and near
      poor children who were up to date for the varicella vaccine increased between 7
      and 8 percentage points more than among nonpoor children after implementation of
      SCHIP. Relative increases among poor and near-poor children were greater in the
      28 Immunization Action Plan areas, in states with high rates of uninsured
      children, and among Hispanics. CONCLUSION: SCHIP seems not to be associated with
      changes in the up-to-date status of poor and near-poor children for the 4:3:1 and
      the 4:3:1:3:3 vaccine series. Vaccine coverage rates increased broadly among all
      income groups between 1995 and 2002.

PMID- 15867018
TI  - The pediatric hybrid observation unit: an analysis of 6477 consecutive patient
      encounters.
AB  - OBJECTIVES: Pediatric observation units (OUs) are becoming more common in
      hospitals throughout the United States, providing physicians with a new
      disposition option for children who are judged to be too ill for home management.
      Some OUs function as "hybrid" units, serving both acutely ill and injured
      observation patients as well as scheduled elective procedure patients. How best
      to utilize this new resource is not yet defined. We studied the utilization of
      our pediatric hybrid OU during the first 2 years of operation to determine (1)
      the spectrum and frequency of diagnoses treated, (2) diagnoses and procedures
      most (and least) likely to attain discharge successfully within 24 hours, and (3)
      whether age was associated with inability to be discharged from the OU within 24
      hours. METHODS: The study setting was a 20-bed hybrid OU located in a pediatric
      tertiary care hospital in Salt Lake City, Utah. The records of all patients
      admitted during the first 2 years of OU operation, from August 1999 through July
      2001, were examined retrospectively. RESULTS: There were 6477 OU admissions: 4189
      (65%) for acutely ill and injured observation patients and 2288 (35%) for
      scheduled elective procedure patients. For the observation patients, median age
      was 2.5 years and median length of stay was 15.5 hours. Common admission
      diagnoses in these patients included enteritis/dehydration (n = 722), orthopedic
      injuries (n = 362), asthma (n = 327), closed head injury (n = 289), urgent
      transfusion/infusion (n = 221), bronchiolitis (n = 212), croup (n = 207),
      abdominal pain (n = 199), cellulitis (n = 177), and nonfebrile seizure (n = 98).
      Overall, 15% of observation patients required subsequent inpatient admission for
      >24-hour stay. Observation diagnoses that were most likely to require inpatient
      admission were hematochezia (60%), viral pneumonia (46%), and bronchiolitis
      (43%). We demonstrated successful OU discharge rates (>85%) for several diagnoses
      not commonly reported: neonatal hyperbilirubinemia, aseptic meningitis, and
      diabetic ketoacidosis in the patient with known diabetes. Among the scheduled
      elective procedure patients, median age was 5.0 years and median length of stay
      was 3.0 hours. Only 1% of these patients required subsequent inpatient admission.
      In both populations, age < or =30 days was associated with increased need for
      inpatient admission, with a relative risk of 1.9 (95% confidence interval: 1.4
      2.6) among the observation patients and 13.9 (95% confidence interval: 3.0-65.0)
      among scheduled procedure patients. CONCLUSION: Our pediatric hybrid OU played an
      important role in the treatment of children who were admitted for observation as
      a result of acute illness or injury, as well as children who required scheduled
      procedures. For both patient types, we identified diagnoses that are most and
      least likely to attain successful discharge within 24 hours. The majority (85%)
      of observation patients were discharged successfully within 24 hours. Successful
      discharge rates for diagnoses that are not commonly managed in other pediatric
      OUs were reported. We identified certain age groups within selected diagnoses
      that may not have been appropriate for the OU.

PMID- 15867019
TI  - Childhood femur fractures, associated injuries, and sociodemographic risk
      factors: a population-based study.
AB  - OBJECTIVE: The objectives of this study were to determine the incidence of femur
      fractures in Colorado children, to assess underlying causes, to determine the
      prevalence and predictors of associated injuries, and to identify potentially
      modifiable risk factors. METHODS: The study population included all Colorado
      residents who were aged 0 to 17 years at the time of injury between January 1,
      1998, and December 31, 2001. Cases of femur fracture were ascertained using the
      population-based Colorado Trauma Registry and International Classification of
      Diseases, Ninth Revision, Clinical Modification codes 820.0 to 821.39. Associated
      injuries with an Abbreviated Injury Scale of 2 or higher were classified into 5
      categories. Poisson regression, small area analysis, and multivariate logistic
      regression were used to identify predictors of femur fractures and associated
      injuries, respectively. RESULTS: During the study period, 1139 Colorado children
      (795 boys, 344 girls) sustained femur fractures, resulting in the incidence of
      26.0 per 100000 person-years. Rates were higher in boys than in girls in all age
      groups (overall risk ratio: 2.19; 95% confidence interval: 1.92-2.47) but did not
      differ by race/ethnicity. Femur fractures that were caused by nonaccidental
      trauma showed more distal and combined shaft + distal pattern; their incidence
      did not differ by gender or race but was higher in census tracts with more single
      mothers and less crowded households. Associated injuries were present in 28.6% of
      the cases, more often in older children. Fatalities occurred only among children
      with associated injuries. Children who were involved in nonaccidental trauma,
      motor vehicle crashes, or auto-pedestrian accidents were 16 to 20 times more
      likely to have associated injuries than those with femur fractures as a result of
      a fall. In small-area analysis, the incidence of femur fractures in infants and
      toddlers was higher in census tracts characterized by higher proportion of
      Hispanics, single mothers, and more crowded households. Among children 4 to 12
      years of age, the incidence was higher in census tracts with fewer single-family
      houses and more crowded households. Finally, the incidence of femur fractures
      among teenagers was higher in rural tracts and those with a higher proportion of
      Hispanics. CONCLUSIONS: Femur fractures and associated injuries remain a major
      cause of morbidity in children. Predictors of femur fractures change with age;
      however, the risk is generally higher among children who live in the areas with
      lower socioeconomic indicators.

PMID- 15867020
TI  - Obesity at the onset of diabetes in an ethnically diverse population of children:
      what does it mean for epidemiologists and clinicians?
AB  - OBJECTIVE: It is often difficult to determine the pathophysiology of childhood
      diabetes at onset, particularly in overweight children, because obesity has been
      associated with both type 1 and type 2 diabetes. We compared children at the
      diagnosis of diabetes in a multiethnic population-based registry to understand
      the epidemiology of the disease during a time of rapidly changing diagnostic and
      treatment norms. METHODS: Incident diabetes was ascertained in Chicagoans who
      were aged 0 to 17 years from 1985 to 2001. We classified as type 2 those with
      polycystic ovary syndrome, acanthosis, or a physician's note indicating type 2 or
      those who reported subsequent use of oral agents (n = 203); 73% of them were also
      obese. Patients with obesity at onset but no other indicator of possible type 2
      (n = 197) were classified as having obesity-related/undetermined type. The
      remaining 842 cases were classified as type 1. Logistic regression analyses were
      conducted. RESULTS: Fully 32% of cases were classified as non-type 1, including
      37% of non-Hispanic blacks, 30% of Latinos, and 14% of non-Hispanic whites. The
      proportion of obesity-undetermined and type 2 increased over the 17 years.
      Comparing the 3 patient groups, type 2 cases were more often female, non-Hispanic
      black, and older and had a first-degree diabetic relative, whereas Latino boys
      were overrepresented among the obese/undetermined. CONCLUSION: Obesity is
      prevalent in youths with newly diagnosed diabetes, particularly during recent
      years. The growth in non-type 1 diabetes in children since 1985 likely reflects
      both a true increase and greater physician awareness of the possibility that type
      2 diabetes may occur in children.

PMID- 15867021
TI  - Influence of gender, race, and ethnicity on suspected fatty liver in obese
      adolescents.
AB  - OBJECTIVES: Fatty liver is a common cause of liver disease in children. However,
      the epidemiology of pediatric fatty liver is limited to single-center case series
      of nonalcoholic fatty liver disease (NAFLD). Obesity and insulin resistance are
      major established risk factors for NAFLD. The role of gender, race, and ethnicity
      on the prevalence of fatty liver in obese children is unknown. METHODS: We
      recruited obese 12th-grade participants from the Child and Adolescent Trial for
      Cardiovascular Health in California, Louisiana, Minnesota, and Texas. Serum
      samples were collected at school when the participants were well. Alanine
      aminotransferase (ALT) was measured by kinetic enzymatic assay, and ALT >40 U/L
      was defined as abnormal. Causes of abnormal ALT other than NAFLD were excluded by
      serum testing. RESULTS: A total of 127 obese students (73 female, 54 male) had a
      mean BMI of 35.2 kg/m2. Unexplained ALT elevation was present in 23% of
      participants overall. The mean ALT for participants with normal values was 28 U/L
      and for participants with an abnormal ALT was 56 U/L. Abnormal ALT was
      significantly more prevalent in boys (44%) than in girls (7%). The prevalence of
      abnormal ALT differed significantly by race and ethnicity (Hispanic: 36%; white:
      22%; black: 14%). Serum ALT value was significantly predicted by the combination
      of gender, race/ethnicity, and BMI. After controlling for gender and BMI,
      Hispanic ethnicity significantly predicted greater ALT than black race.
      CONCLUSIONS: In a national, school-based sample of obese adolescents, boys were 6
      times more likely than girls to have an unexplained elevated ALT. Given that
      participants were well and causes of chronic liver disease were excluded, we
      speculate that obese adolescent boys have an increased prevalence of fatty liver
      compared with obese adolescent girls. This population-based study also supports
      the hypothesis that NAFLD is more common in Hispanic adolescents. These findings
      have implications for both disease screening and studies of fatty liver
      pathophysiology.

PMID- 15867022
TI  - Affect and sexual behavior in adolescents: a review of the literature and
      comparison of momentary sampling with diary and retrospective self-report methods
      of measurement.
AB  - OBJECTIVE: Assessment of mental health is important in understanding sexual risk
      behavior in adolescents, yet few studies have examined how affect is directly
      related to sexual behavior. Momentary sampling (MS) methods permit real-time
      assessment of affect in relation to specific events and embed the collected data
      in the context of the respondent's moment-to-moment life. The objectives of this
      study were to review the literature on affect and sexual behavior and to compare
      the feasibility and acceptability of MS with diaries and retrospective self
      report as a means of collecting temporally relevant data on affect and sexual
      behavior in adolescents. METHODS: Sexually active, nondepressed adolescent
      outpatients who were aged 15 to 18 years were randomly assigned to a schedule of
      the 3 methods of data collection for 2 weeks each. All participants completed a
      retrospective self-report by interview at the end of each 2-week period. In the
      diary arm, participants completed twice-daily paper-and-pencil diary cards, which
      were returned by mail. In the MS arm, participants used 2-way pagers to respond
      to several random pages per day. Primary outcomes included rates of completion
      (diaries vs MS reports) and the participants' tolerance of and preferences for
      the methods. A secondary outcome was the agreement in means for positive and
      negative affect and in report of days on which substance use and sexual activity
      occurred. Associations of affect with contextual factors and with sexual activity
      were also explored in the MS arm. RESULTS: Ten youths completed 30 of 30
      retrospective self-reports (100%, 3 per participant, by design), 254 of 280
      diaries (91%; mean: 25.4 per participant), and 442 of 600 MS reports (74%; mean:
      44.2 per participant). Most participants preferred the MS method to the diaries
      or retrospective self-report. Affect scores and reports of sexual activity and
      substance use were correlated among the methods. Measured with MS, affect was
      found to differ by location, companionship, and thoughts when paged; notably,
      positive affect was highest when participants reported thoughts about sex. There
      was no difference in affect before versus after coitus. CONCLUSIONS: The results
      of this study suggest that MS in adolescents is feasible and preferred and
      provides contextual, temporally relevant, event-level data on affect and sexual
      activity that are not readily measured with traditional methods. Future research
      using MS methods will be important in increasing our understanding of the link
      between affect and sexual behavior and inform the development of improved risk
      reduction interventions for adolescents.

PMID- 15867023
TI  - Comparison of parent and child reports of emotional trauma symptoms in pediatric
      outpatient settings.
AB  - OBJECTIVE: Exposure to emotionally traumatic events is common among children who
      are treated in pediatric medical care settings, and it is important to recognize
      the emotional reactions that children might develop as a response to the trauma.
      Practitioners sometimes rely on parental reports of the child's emotional
      reactions, but these reports may be biased by the parent's own posttraumatic
      symptoms. Understanding the differences between parent and child reports of the
      child's emotional symptoms is essential to guide proper diagnosis and care. This
      study evaluated discrepancies in parental versus child reports of the child's
      emotional trauma symptoms in pediatric medical care settings. METHODS: We
      enrolled children and adolescents (age: 8-19) who had not previously received a
      diagnosis of a psychiatric disorder and were treated in pediatric specialty care
      clinics at Mount Sinai Medical Center in New York. We used the UCLA posttraumatic
      stress reaction index, child, adolescent, and parent versions, to evaluate child
      and parent reports of symptoms of posttraumatic stress disorder (PTSD) in the
      child. The Impact of Event Scale was used to evaluate the parents' own
      posttraumatic symptoms. We conducted a "best estimate" psychiatric diagnostic
      procedure to determine whether the child met diagnostic criteria for PTSD and
      evaluated the association between the diagnostic status (as determined by the
      "best estimate" procedure) and the results of the questionnaires. RESULTS: A
      total of 115 patients and parents consented to the study, and 76 completed the
      evaluation. Sixty-four percent of the parents identified the child's traumatic
      experience as their own most traumatic experience, too. The child's self-report
      of PTSD symptoms was significantly correlated with the diagnosis of PTSD in the
      child. In contrast, parents' reports of their child's PTSD symptoms were not
      significantly associated with the child's diagnosis. Parents' own posttraumatic
      symptoms were associated with parental reports of the child's overall PTSD
      symptoms (correlation coefficient: 0.283). CONCLUSIONS: When a child is
      emotionally traumatized, the parent's own posttraumatic stress may influence his
      or her report and interpretation of the child's symptoms. Clinicians who evaluate
      children and adolescents for PTSD in medical care settings should directly seek
      the child's report and should not rely exclusively on parental reports. Parental
      reports of a child's PTSD symptoms can offer insights into the parent's own level
      of posttraumatic stress.

PMID- 15867024
TI  - Increased attack rate of meningococcal disease in children with a pregnant
      mother.
AB  - OBJECTIVE: To investigate the relationship between meningococcal disease and
      family composition, especially pregnancy in mothers. METHODS: This was a
      retrospective matched case-control study. Case patients were children (aged 0-18
      years) who had meningococcal disease and were admitted to our hospital from 1990
      to 2002. Children who were admitted to 1 of the general pediatric wards of the
      hospital during the same period and did not have meningococcal disease served as
      control subjects. One control subject (matched according to gender, age, and
      year, and season of admission) was enrolled for each case patient. Parents of
      case patients and control subjects were asked to fill out a questionnaire on
      family composition, birth dates of siblings, and pregnancy at the time of
      hospital admission. RESULTS: A total of 88 matched case-control pairs were
      included. In the case group, 17 (19%) mothers reported having been pregnant at
      the time of hospitalization of their child, compared with 2 (2%) in the control
      group. Other family characteristics were not different. After adjustment for
      confounding factors, pregnancy of mothers remained a significant risk factor for
      meningococcal disease in children (odds ratio: 11.7; 95% confidence interval: 2.6
      53.9). CONCLUSIONS: Meningococcal disease in children was highly associated with
      pregnancy of the patient's mother during hospitalization. Mechanisms by which the
      presence of a pregnant mother in a family affects the attack rate of
      meningococcal disease in her children need additional investigation.

PMID- 15867025
TI  - Assessment of perinatal hepatitis B and rubella prevention in New Hampshire
      delivery hospitals.
AB  - OBJECTIVE: To evaluate current performance on recommended perinatal hepatitis B
      and rubella prevention practices in New Hampshire. METHODS: Data were extracted
      from 2021 paired mother-infant records for the year 2000 birth cohort in New
      Hampshire's 25 delivery hospitals. Assessment was done on the following: prenatal
      screening for hepatitis B and rubella, administration of the hepatitis B vaccine
      birth dose to all infants, administration of hepatitis B immune globulin to
      infants who were born to hepatitis B surface antigen-positive mothers, rubella
      immunity, and administration of in-hospital postpartum rubella vaccine to rubella
      nonimmune women. RESULTS: Prenatal screening rates for hepatitis B (98.8%) and
      rubella (99.4%) were high. Hepatitis B vaccine birth dose was administered to
      76.2% of all infants. All infants who were born to hepatitis B surface antigen
      positive mothers also received hepatitis B immune globulin. Multivariate logistic
      regression showed that the month of delivery and infant birth weight were
      independent predictors of hepatitis B vaccination. The proportion of infants who
      were vaccinated in January and February 2000 (48.5% and 67.5%, respectively) was
      less than any other months, whereas the proportion who were vaccinated in
      December 2000 (88.2%) was the highest. Women who were born between 1971 and 1975
      had the highest rate of rubella nonimmunity (9.5%). In-hospital postpartum
      rubella vaccine administration was documented for 75.6% of nonimmune women.
      CONCLUSION: This study documents good compliance in New Hampshire's birthing
      hospitals with national guidelines for perinatal hepatitis B and rubella
      prevention and highlights potential areas for improvement.

PMID- 15867026
TI  - Quality-adjusted life-years lack quality in pediatric care: a critical review of
      published cost-utility studies in child health.
AB  - OBJECTIVES: Cost-utility analysis in which health benefits are quantified in
      terms of quality-adjusted life-years (QALYs) has now become the standard type of
      cost-effectiveness analysis. These studies are potentially influential in
      determining the extent of funding for particular pediatric interventions, and so
      their methodologic quality is extremely important. The objective of this study
      was twofold: first, to critically appraise published cost-utility analyses of
      interventions in child and adolescent health care in terms of the methods used to
      derive QALYs and, second, to discuss unresolved methodologic issues that are
      pertinent to the measurement of QALYs in pediatric populations. METHODS: A
      comprehensive search using computerized databases (including Medline, Embase,
      Econlit, and databases specific to economic evaluation), Web searches, and
      citation tracking was undertaken to identify cost-utility studies of
      interventions that were aimed at those who were younger than 16 years and
      published before April 2004. The methods of individual studies were compared with
      the recognized published guidelines of the US Panel on Cost-Effectiveness in
      Health and Medicine and the National Institute for Clinical Excellence in England
      and Wales, which recommend the use of a generic health state classification
      system (eg, Health Utility Index, EuroQol-5D), a choice-based valuation method
      (eg, standard gamble or time trade-off) and preferences of the general public in
      estimating QALYs. Studies therefore were categorized and evaluated according to
      the methods used to describe the health state, the valuation technique, and
      source of preferences. RESULTS: Fifty-four studies were reviewed, 34 (63%) of
      which were published in the past 5 years. A generic health status classification
      instrument was used in 22 (35%) cases; the remainder developed study-specific
      health state descriptions or elicited preferences directly from patients or
      proxies. In 3 (5%) cases, sources were unclear. Preference weights were elicited
      using choice-based techniques in 28 (42%) cases, either as tariffs for health
      status classification instruments (17 cases) or by directly valuing health state
      descriptions or patient health (11 cases). Preferences of the general public were
      used in only 23 (37%) cases. Four studies aggregated QALYs for mother/child or
      parents/child pairs without giving any theoretical justification. Although there
      was an increasing tendency for studies to use generic health status
      classification instruments, choice-based methods, and preferences of the general
      public, the majority of studies still did not adhere to these standard
      recommendations even in the period between January 2000 and March 2004. Despite
      increasing standardization in the methods advocated for economic evaluation over
      the past 10 years, there remains extensive variation in the actual methods used
      by researchers to calculate QALYs for children and adolescents. It is unclear
      whether these results suggest poor practice or a set of positive (or reactive)
      choices made by analysts in a methodologically uncertain area in which specific
      guidance is lacking regarding how to address the complexities of pediatric
      outcomes within the QALY framework. Many aspects of QALY measurement in children
      are not yet fully developed. In particular, there is (1) a lack of appropriate
      health state classification instruments that take account of the dynamics of
      child development, (2) a lack of health state classification instruments for use
      in children and infants who are younger than 5 years, and (3) the need to
      understand fully the role of proxies for measuring and valuing child health.
      Additional research efforts are also required to develop methods that account for
      the health benefits of parents or caregivers of the child and to consider the
      implications of combining different forms of utility measurement in childhood and
      adulthood. CONCLUSIONS: Although variations from standard recommendations may be
      attributable to poor practice among researchers who are either unaware of these
      recommendations or choose not to follow them, they could equally be the result of
      attempts to make research more rigorous and more defensible than it might be if
      the standard recommendations were followed. There are 4 potential approaches to
      conducting cost-utility analysis in pediatric populations: (1) the explicit
      development of a generic instrument designed to be applicable across both child
      and adult populations (likely to be difficult in practice), (2) insistence on use
      of a generic instrument developed for adults, (3) the use of generic instruments
      specifically developed for children without being concerned about comparability
      with interventions aimed at adults, and (4) abandoning attempts to use single
      outcome measures that combine mortality with quality weights. In the absence of a
      clear way forward, it is suggested that an expert panel be convened to debate and
      further consider these potential solutions and recommendations for best practice
      and future research. In the interim, comparisons of the relative cost
      effectiveness reported as cost per QALY gained across interventions for different
      diseases and populations should be treated with extreme caution.

PMID- 15867027
TI  - Community-acquired pneumonia in children: quantifying the burden on patients and
      their families including decrease in quality of life.
AB  - OBJECTIVES: Childhood respiratory infections have an important impact on society
      and are a frequent cause of physician visits, consumption of antibiotics and over
      the-counter drugs, work loss, and reduction of quality of life. The aim of this
      study was to assess the burden of community-acquired pneumonia (CAP) on children
      and their families, including quantification of expenses and decrease in quality
      of life. METHODS: Patients <3 years old with pneumonia were enrolled in 3 sites
      in southern Israel: pediatric wards, the pediatric emergency department, and a
      primary health clinic. In the primary health clinic, the diagnosis was based on
      clinical judgment, and in the hospital the diagnosis was based on the World
      Health Organization Standardization of Interpretation of Chest Radiographs for
      the diagnosis of CAP in children. Data regarding the children's medical history
      and various aspects of direct and indirect burden were gathered every 2 to 3 days
      during the 29 days of follow-up. The patients' parents were asked to give the
      names of 2 healthy children who could serve as controls from among the child's
      friends, neighbors, or day care center attendees. RESULTS: Two-hundred thirteen
      children with pneumonia were enrolled: 34 (16.0%) in the pediatric wards, 73
      (34.2%) in the pediatric emergency department, and 106 (49.8%) in the primary
      pediatric clinic. The control group consisted of 99 children. During the 29
      follow-up days, hospitalized children had the most severe and prolonged symptoms,
      followed in decreasing order by children seen at the emergency department,
      primary health clinic, and controls: The mean +/- standard deviation (SD) of
      febrile days was 4.9 +/- 2.8, 4.8 +/- 3.1, 3.3 +/- 2.5, and 1.4 +/- 3.3,
      respectively (statistically significant between any patient group and the control
      group). The mean duration of respiratory distress +/- SD was 3.8 +/- 5.6, 2.8 +/-
      4.4, 2.2 +/- 4.4, and 0.4 +/- 1.8 days, respectively (statistically significant
      between any patient group and the control group). The median duration of
      nonroutine days as judged by the parents was 13, 8, 7, and 0, respectively. The
      mean number of workdays lost by working mothers +/- SD was 4.2 +/- 4.8, 2.0 +/-
      2.6, 1.7 +/- 1.9, and 0.2 +/- 0.9, respectively (between any patient group and
      the control group). The quality-of-life-questionnaire analysis reveals
      statistically significant differences with regard to all 11 questions asked
      between any of the patient groups and the control group. There was a clear trend
      toward decreasing quality of life from the control group to the primary health
      clinic, pediatric emergency department, and pediatric wards groups. CONCLUSIONS:
      CAP in children causes a significant burden on both patients and their families,
      including substantial expenses, loss of routine, and decrease in quality of life.

PMID- 15867028
TI  - Cost-effectiveness of conjugate meningococcal vaccination strategies in the
      United States.
AB  - CONTEXT: The US Food and Drug Administration approved a meningococcal conjugate
      A/C/Y/W-135 vaccine (MCV-4) for use in persons aged 11 to 55 years in January,
      2005; licensure for use in younger age groups is expected in 2 to 4 years.
      OBJECTIVE: To evaluate and compare the projected health and economic impact of
      MCV-4 vaccination of US adolescents, toddlers, and infants. DESIGN: Cost
      effectiveness analysis from a societal perspective based on data from Active
      Bacterial Core Surveillance (ABCs) and other published and unpublished sources.
      Sensitivity analyses in which key input measures were varied over plausible
      ranges were performed. SETTING AND PATIENTS: A hypothetical 2003 US population
      cohort of children 11 years of age and a 2003 US birth cohort. INTERVENTIONS:
      Hypothetical routine vaccination of adolescents (1 dose at 11 years of age),
      toddlers (1 dose at 1 year of age), and infants (3 doses at 2, 4, and 6 months of
      age). Each vaccination scenario was compared with a "no-vaccination" scenario.
      MAIN OUTCOME MEASURES: Meningococcal cases and deaths prevented, cost per case
      prevented, cost per life-year saved, and cost per quality-adjusted life-year
      saved. RESULTS: Routine MCV-4 vaccination of US adolescents (11 years of age)
      would prevent 270 meningococcal cases and 36 deaths in the vaccinated cohort over
      22 years, a decrease of 46% in the expected burden of disease. Before program
      costs are counted, adolescent vaccination would reduce direct disease costs by
      $18 million and decrease productivity losses by $50 million. At a cost per
      vaccination (average public-private price per dose plus administration fees) of
      $82.50, adolescent vaccination would cost society $633000 per meningococcal case
      prevented and $121000 per life-year saved. Key variables influencing results were
      disease incidence, case-fatality ratio, and cost per vaccination. The cost
      effectiveness of toddler vaccination is essentially equivalent to adolescent
      vaccination, whereas infant vaccination would be much less cost-effective.
      CONCLUSIONS: Routine MCV-4 vaccination of US children would reduce the burden of
      disease in vaccinated cohorts but at a relatively high net societal cost. The
      projected cost-effectiveness of adolescent vaccination approaches that of
      recently adopted childhood vaccines under conditions of above-average
      meningococcal disease incidence or at a lower cost per vaccination.

PMID- 15867029
TI  - Assuring adequate health insurance: results of the National Survey of Children
      with Special Health Care Needs.
AB  - OBJECTIVE: The purpose of this article is to report the findings of the 2001
      National Survey of Children With Special Health Care Needs regarding the extent
      to which children with special health care needs (CSHCN) have access to public or
      private health insurance that meets their needs. METHODOLOGY: As part of its
      effort to develop systems of care for CSHCN, the US Maternal and Child Health
      Bureau established a health insurance core outcome. Successful attainment was
      measured on the basis of whether the child met 3 distinct components at the time
      of the interview: presence of public or private coverage; continuity of coverage
      over the previous 12 months; and adequacy of coverage. Adequacy of coverage was
      measured from the family's perspective of whether their insurance covered needed
      services, covered a reasonable share of costs, and allowed families to see the
      providers they felt were best for their child. Bivariate and multivariate
      statistical methods were used to assess independent predictors of respondents
      meeting the health insurance core outcome. RESULTS: Results of the survey
      indicated that 59.6% of CSHCN nationally met the health insurance core outcome
      using the 3 components of presence of insurance coverage, continuity of coverage,
      and adequacy of coverage. Poverty status, race/ethnicity, and functional ability
      were significant factors in whether a child met the health insurance core outcome
      as well as each of the 3 components. Of Hispanic and non-Hispanic black CSHCN,
      45.2% and 57.6%, respectively, met the health insurance core outcome, compared
      with 62.5% of their white counterparts. Children with the most limited functional
      ability were 50% less likely to meet the health insurance core outcome than CSHCN
      without limitations. More than 10% of Hispanic CSHCN were uninsured at the time
      of the interview, and 20% of Hispanic CSHCN experienced gaps in coverage.
      Although insurance met the needs of most families, more than one fourth of
      families reported that uncovered costs were not reasonable. Children who did not
      meet the health insurance core outcome were also more likely to have unmet needs.
      CONCLUSIONS: Results of the survey demonstrated that although the majority of
      CSHCN have adequate health insurance, additional work is needed to improve the
      adequacy of insurance, particularly for children below the poverty line, Hispanic
      children, and children with the most limited functional ability. The survey
      results also demonstrated the importance of continuous and adequate health
      insurance, because children who met the health insurance core outcome had fewer
      unmet needs.

PMID- 15867030
TI  - Early-onset group B streptococcal disease in the era of maternal screening.
AB  - BACKGROUND: With the widespread implementation of intrapartum antibiotic
      prophylaxis (IAP), the rate of early-onset neonatal sepsis and meningitis caused
      by Streptococcus agalactiae (group B streptococcus [GBS]) has decreased
      dramatically, especially in term infants. However, cases of GBS disease continue
      to occur despite IAP and incur significant morbidity and mortality. Inaccurate
      screening results, improper implementation of IAP, or antibiotic failure all may
      contribute to persistent disease. OBJECTIVE: To determine if clinical,
      procedural, or microbiologic factors influenced persistent early-onset GBS
      disease (EOGBS) cases in a single large maternity service after the institution
      of a screening-based protocol for IAP. METHODS: Retrospective review of all cases
      of culture-proven EOGBS at the Brigham and Women's Hospital (Boston, MA) from
      1997 to 2003. Serotyping and surface protein analyses were performed on available
      disease isolates. RESULTS: A total of 67260 infants were live-born during this
      period. Twenty-five cases of EOGBS (0.37 of 1000 live births) were identified.
      The overall incidence of EOGBS progressively decreased with different approaches
      to IAP. Of the 25 cases identified after institution of a screening-based
      protocol, 17 (68%) occurred in term infants (1 death), and 8 (32%) occurred in
      preterm infants (3 deaths). Among the mothers of term infants, 14 of 17 (82%) had
      been screened GBS negative; 1 was GBS unknown. More than half of the mothers of
      term infants who had screened GBS negative (8 of 14) had intrapartum risk factors
      for neonatal infection but did not receive antibiotics before delivery. Ten of
      the 17 term infants were evaluated for infection because of clinical signs of
      illness, and the remainder were evaluated because of intrapartum sepsis risk
      factors. Of the mothers of preterm infants, by the time of delivery 3 of 8 had
      been documented as GBS positive, 2 of 8 had been documented GBS negative, and 3
      of 8 remained unknown. Only 1 of 25 women received adequate IAP, but the isolate
      was resistant to the administered antibiotic (clindamycin). Antibiotic resistance
      was not a factor in any other case, and no dominant serovariant was identified
      among tested isolates. Procedural errors (lack of recognition of documented GBS
      colonization or failure to evaluate infants at risk for sepsis) were identified
      in 4 cases. CONCLUSIONS: The majority of the remaining cases of EOGBS occurred in
      infants whose mothers screened negative for GBS colonization. Even in the setting
      of a maternal GBS-screening program, efforts to evaluate and treat infants with
      intrapartum clinical risk factors for early-onset sepsis remain important. Until
      effective vaccines against GBS are available for clinical use, development and
      implementation of rapid and sensitive techniques for screening for GBS status and
      antibiotic susceptibility at presentation may help prevent additional cases of
      invasive GBS disease.

PMID- 15867031
TI  - Changes in the classification of sudden unexpected infant deaths: United States,
      1992-2001.
AB  - BACKGROUND: Sudden infant death syndrome (SIDS) makes up the largest component of
      sudden unexpected infant death in the United States. Since the first
      recommendations for supine placement of infants to prevent SIDS in 1992, SIDS
      postneonatal mortality rates declined 55% between 1992 and 2001. OBJECTIVE: The
      objective of this analysis was to examine changes in postneonatal mortality rates
      from 1992 to 2001 to determine if the decline in SIDS was due in part to a shift
      in certification of deaths from SIDS to other causes of sudden unexpected infant
      death. In addition, the analysis reviews the change in mortality rates attributed
      to the broad category of sudden unexpected infant death in the United States
      since 1950. METHODS: US mortality data were used. The International
      Classification of Diseases (ICD) chapters "Symptoms, Signs, and Ill-Defined
      Conditions" and "External Causes of Injury" were considered to contain all causes
      of sudden unexpected infant death. The following specific ICD (ninth and tenth
      revisions) underlying-cause-of-death categories were examined: "SIDS," "other
      unknown and unspecified causes," "suffocation in bed," "suffocation-other,"
      "aspiration," "homicide," and "injury by undetermined intent." The average annual
      percentage change in rates was determined by Poisson regression. An analysis was
      performed that adjusted mortality rates for changes in classification between ICD
      revisions. RESULTS: The all-cause postneonatal mortality rate declined 27% and
      the postneonatal SIDS rate declined 55% between 1992 and 2001. However, for the
      period from 1999 to 2001 there was no significant change in the overall
      postneonatal mortality rate, whereas the postneonatal SIDS rate declined by
      17.4%. Concurrent increases in postneonatal mortality rates for unknown and
      unspecified causes and suffocation account for 90% of the decrease in the SIDS
      rate between 1999 and 2001. CONCLUSIONS: The failure of the overall postneonatal
      mortality rate to decline in the face of a declining SIDS rate in 1999-2001
      raises the question of whether the falling SIDS rate is a result of changes in
      certifier practices such that deaths that in previous years might have been
      certified as SIDS are now certified to other non-SIDS causes. The observation
      that the increase in the rates of non-SIDS causes of sudden unexpected infant
      death could account for >90% of the drop in the SIDS rates suggests that a change
      in classification may be occurring.

PMID- 15867032
TI  - Racial and ethnic differences in asthma diagnosis among children who wheeze.
AB  - BACKGROUND: Racial and ethnic disparities exist in reported childhood asthma
      prevalence, but it is unclear if disparities stem from true prevalence
      differences or a different likelihood of receiving a diagnosis from a health
      professional. Concern has been raised that asthma may be underdiagnosed,
      particularly among minority children who have more restricted access to high
      quality health care. OBJECTIVE: To examine racial/ethnic differences among
      currently symptomatic children in acquiring an asthma diagnosis to determine if
      relative underdiagnosis among minorities exists. Children for whom no symptoms
      were reported (a group that includes those with well-controlled symptoms) were
      excluded from the analysis. METHODS: The 1999 National Health Interview Survey
      includes a nationally representative sample of children with reported wheezing
      symptoms. We included children 3 to 17 years old in the study and analyzed
      racial/ethnic differences in asthma diagnosis, controlling for young age, gender,
      parental education, single-parent household, central-city residence, region of
      residence, health insurance, having a usual place of care, and parent-reported
      severity of wheezing symptoms. RESULTS: Among those reported to have wheezed in
      the past year (n = 946), 83% of Puerto Rican, 71% of non-Hispanic black, and 65%
      of Mexican children were diagnosed with asthma compared with 57% of non-Hispanic
      white children. Using non-Hispanic white children as the reference group, the
      approximate adjusted relative risk for physician diagnosis of asthma given
      wheezing in the past year was 1.43 (95% confidence interval [CI]: 1.04, 1.63) for
      Puerto Rican, 1.22 (95% CI: 1.03, 1.37) for non-Hispanic black, and 1.19 (95% CI:
      0.94, 1.39) for Mexican children. Minority children were reported to have greater
      severity of wheezing symptoms. Even after accounting for this increased severity,
      children in racial and ethnic minority groups were as or more likely to have a
      reported asthma diagnosis than non-Hispanic white children. CONCLUSIONS: Our
      findings do not provide evidence for the hypothesis that symptomatic minority
      children are underdiagnosed with asthma compared with non-Hispanic white
      children. To the contrary, among currently symptomatic children, minority
      children were more likely to be diagnosed than non-Hispanic white children even
      after accounting for the higher wheezing severity among minority children.

PMID- 15867033
TI  - Posttraumatic stress responses in children: awareness and practice among a sample
      of pediatric emergency care providers.
AB  - BACKGROUND: Research suggests that up to 4 of 5 children experience symptoms of
      an acute stress response (ASR) after a motor vehicle-related injury, and
      approximately 25% will develop posttraumatic stress disorder (PTSD). The degree
      to which physicians recognize this problem has not been reported. Our objective
      was to evaluate current awareness and practices of a cohort of pediatric
      emergency care providers regarding posttraumatic stress in children. METHODS:
      Participants were identified from a list of the American Academy of Pediatrics
      Section on Emergency Medicine and surveyed on their awareness of ASR after motor
      vehicle-related injury, risk factors for developing PTSD, and practices regarding
      emergency department (ED) interventions. Surveys from physicians not practicing
      clinical emergency medicine were excluded. RESULTS: Of 322 surveys returned, 287
      responses met inclusion criteria. Among these respondents, 198 (69%) were
      pediatric emergency medicine board certified or eligible and 260 (91%) practiced
      in a designated pediatric ED. Only 20 of 287 respondents (7%) believed that
      children were likely to develop symptoms of posttraumatic stress at levels
      previously described. Also in contrast to recent literature, 248 respondents
      (86%) felt that severity of injury was associated with future development of
      PTSD. Associated parental injury was identified accurately as a risk factor by
      250 respondents (87%). Of interest, only 31 respondents (11%) were aware of any
      available tools to assess risk for PTSD. In addition, 56 of 287 respondents (20%)
      indicated that they would not use such tools in the ED, most commonly citing time
      and cost constraints. Finally, only 52 respondents (18%) reported giving any
      verbal guidance and only 9 (3%) provided any written instructions about
      posttraumatic stress to their patients and families. CONCLUSIONS: Findings
      suggest that physicians underestimate the likely development of an ASR and PTSD
      in the pediatric population. At present, few physicians offer written or even
      verbal instruction related to the development of posttraumatic symptoms.
      Physician education along with a systematic approach of assessment and
      intervention is necessary to address the gap between underrecognition of this
      concern and desired clinical practice.

PMID- 15867034
TI  - Completeness and complexity of information available to parents from newborn
      screening programs.
AB  - BACKGROUND: In 2000, the American Academy of Pediatrics (AAP) Task Force on
      Newborn Screening published a blueprint for the future of newborn screening that
      included recommendations for information provided to parents about screening.
      OBJECTIVES: To evaluate the completeness of educational material provided by
      newborn-screening programs and to measure the reading level and complexity of the
      material. METHODS: Telephone survey of newborn-screening programs (n = 51)
      followed by content analysis of educational material. RESULTS: All 51 programs
      responded (response rate: 100%); 47 of these programs made educational material
      available. None of the material included all elements recommended in the
      blueprint. Benefits of screening (98%) and how parents would be notified of
      results (87%) were included more often than the risks of screening (19%),
      possibility of a false-positive result (13%), importance of (34%) and how to
      respond to (28%) a positive result, and the storage and use of residual samples
      (11%). The median readability grade level was 10. Grade-level complexity of the
      material was not associated with completeness according to the AAP criteria.
      CONCLUSIONS: Parent educational materials for newborn-screening programs do not
      meet the standard recommended by the AAP, and there are important variations
      between programs in the information provided to parents. Continuing research is
      needed to measure progress toward the goals outlined within the blueprint and to
      assess how these changes impact the care provided through newborn-screening
      programs.

PMID- 15867035
TI  - Telemedicine reduces absence resulting from illness in urban child care:
      evaluation of an innovation.
AB  - BACKGROUND: Common acute illness challenges everyone involved in child care.
      Impoverished inner-city families, whose children are most burdened by morbidity
      and whose reliance on child care is most important, are those least equipped to
      deal with this challenge. OBJECTIVE: To assess the impact of telemedicine on
      absence from child care due to illness (ADI). DESIGN/METHODS: A before-and-after
      design with historical and concurrent controls was used to study ADI in 5 inner
      city child care centers in Rochester, New York, between January 1, 2001, and June
      30, 2003. Enrollment averaged 138 children per center, of whom Medicaid covered
      66%. Center 5 provided only concurrent controls. Telemedicine service began in
      the first 4 centers in a staggered fashion starting in May 2001. Baseline data on
      ADI before availability of telemedicine were collected in each center for a
      minimum of 18 weeks. The telemedicine model for diagnosis and treatment of common
      acute problems involved both real-time and store-and-forward information exchange
      between a child and telemedicine assistant in child care and an office-based
      telemedicine clinician. Devices used were an all-purpose digital camera (with
      attachments designed to facilitate capture of ear, nose, throat, skin, and eye
      images) and an electronic stethoscope. ADI indexed illness that had interrupted
      care and education for children and burdened both parents and the community with
      work loss and health care-related costs. Detailed attendance records and staff
      and parent interviews provided data. The total number of days of attendance
      expected from all registered children over the course of a week (total child
      days) served as the denominator in calculating rates for ADI. The center-week
      served as the primary unit of analysis. This study is descriptive in character;
      statistics are not inferential but instead serve to summarize observations.
      RESULTS: For the 400 weeks of valid observations contributed by the 5 centers,
      the mean ADI was 6.41 absences per 100 child-days per week. In bivariate
      analysis, predictors of ADI were children's mean age, child care center,
      proportion of children covered by Medicaid, season of the year, and availability
      of telemedicine. ADI during weeks with telemedicine (4.07 absences per 100 child
      days) was less than half that during weeks without telemedicine (8.78 absences
      per 100 child-days). After adjusting for potentially confounding variables using
      the generalized estimating equations method, telemedicine remained the strongest
      predictor of ADI. A 63% reduction in ADI was attributable to telemedicine, an
      effect similar to the 59% variation in ADI with season of the year. During the
      201 total weeks that telemedicine services were available, 940 telemedicine
      encounters occurred. Telemedicine clinicians for these 940 encounters recommended
      exclusion from child care for 7.0% and in-person visits for 2.8% of the children.
      In surveys, parents indicated that 91.2% of telemedicine contacts allowed them to
      stay at work and that 93.8% of problems managed by telemedicine would otherwise
      have led to an office or emergency department visit. CONCLUSIONS: Telemedicine
      holds substantial potential to reduce the impact of illness on health and
      education of children, on time lost from work in parents, and on absenteeism in
      the economy.

PMID- 15867036
TI  - A content analysis of e-mail communication between primary care providers and
      parents.
AB  - BACKGROUND: E-mail exchange between parents of patients and providers has been
      cited by the Institute of Medicine as an important aspect of contemporary
      medicine; however, we are unaware of any data describing actual exchanges.
      OBJECTIVE: The purpose of this study was to evaluate the content of e-mails
      between providers and parents of patients in pediatric primary care, as well as
      parent attitudes about e-mail. DESIGN/METHODS: Over a 6-week period, all e-mail
      exchanges between 2 primary care pediatricians and their patients' parents were
      evaluated and coded. An exchange was defined as the e-mails between parent and
      primary care provider about a single inquiry. Parents also completed a
      questionnaire regarding this service. RESULTS: Of 55 parents, 54 (98%) agreed to
      have their e-mails with their pediatrician reviewed. The 54 parents generated 81
      e-mail exchanges; 86% required only 1 e-mail response from the pediatrician, and
      the other 14% required an average of 1.9 responses. E-mail inquiries were all for
      nonacute issues (as judged by S.G.A.) and included inquiries about a medical
      question (n = 43), medical update (n = 20), subspecialty evaluation (n = 9), and
      administrative issue (n = 9). The 81 exchanges resulted in 9 appointments, 21
      phone calls, 4 subspecialty referrals, 34 prescriptions or recommendations for
      over-the-counter medications, 11 administrative tasks, and 1 radiograph. Of 91
      pediatrician-generated e-mails, 39% were sent during the workday (9 am to 5 pm,
      Monday to Friday), 44% were sent on weeknights, and 17% were sent on weekends.
      During the study period, the 2 physicians estimated an average of 30 minutes/day
      spent responding to e-mail. Of the 54 parents, 45 (83%) returned the survey; 93%
      were mothers and 86% had completed college. Ninety-eight percent were very
      satisfied with their e-mail experience with their pediatrician. Although 80% felt
      that all pediatricians should use e-mail to communicate with parents and 65%
      stated they would be more likely to choose a pediatrician based on access by e
      mail, 63% were unwilling to pay for access. CONCLUSIONS: This is the first study
      to describe actual e-mail exchange between parents and their providers. Exchanges
      seem to be different from those generated by the telephone, with more e-mails
      related to medical versus administrative issues and more resulting in office
      visits. Approximately 1 in 4 exchanges result in multiple e-mails back and forth
      between parent and provider. Parents who have actually exchanged e-mails with
      their providers overwhelmingly endorse it, although they are reluctant to pay for
      it.

PMID- 15867037
TI  - Early death, morbidity, and need of treatment among extremely premature infants.
AB  - OBJECTIVE: To determine outcomes, in terms of perinatal and early death, need for
      treatment, and morbidity at the time of discharge home, among extremely preterm
      infants. DESIGN: A prospective observational study of all infants with a
      gestational age (GA) of 22 to 27 completed weeks or a birth weight of 500 to 999
      g who were born in Norway in 1999 and 2000. RESULTS: Of 636 births, 174 infants
      (27%) were stillborn or died in the delivery room, 86 (14%) died in the NICU, and
      376 (59%) were discharged from the hospital. The risk of being registered as
      stillborn or not being resuscitated increased with decreasing GA below 25 weeks.
      The survival rates for all births and for infants admitted to a NICU were,
      respectively, 0% for <23 weeks, 16% and 39% for 23 weeks, 44% and 60% for 24
      weeks, 66% and 80% for 25 weeks, 72% and 84% for 26 weeks, 82% and 93% for 27
      weeks, and 69% and 90% for >27 weeks. For the survivors, days of mechanical
      ventilation decreased from a median of 37 days to 3 days and the proportion in
      need of oxygen at 36 weeks' postconceptional age decreased from 67% to 26% at 23
      and 27 weeks' GA, respectively. At 40 weeks' postconceptional age, the respective
      figures were 11% and 6%. The proportion with retinopathy of prematurity (ROP)
      requiring treatment decreased from 33% for GA of 23 weeks to 0% for >25 weeks.
      Periventricular hemorrhage of more than grade 2 occurred for 6% of the survivors
      and significant periventricular leukomalacia occurred for 5%, with no significant
      association with GA. The proportion of survivors without severe neurosensory or
      pulmonary morbidity increased from 44% for 23 weeks' to 86% for 27 weeks' GA.
      Apart from ROP, the morbidity rate was not associated with GA. CONCLUSIONS: The
      survival rate was high and the morbidity rate at discharge home was low in the
      present study, compared with previous population-based studies. With the
      exception of ROP, the morbidity rates among the survivors were not higher at the
      lowest GAs, possibly because withholding treatment was considered more acceptable
      for the most immature infants. The need for intensive care increased markedly for
      survivors with the lowest GAs.

PMID- 15867039
TI  - Influence of swaddling on sleep and arousal characteristics of healthy infants.
AB  - OBJECTIVE: Swaddling is an old infant care practice. It was reported to favor
      sleep and to reduce crying among irritable infants. There are few data on the
      physiologic effects of swaddling on infants' sleep-wake characteristics. This
      study was conducted to evaluate whether swaddling influences infants' arousal
      thresholds for environmental auditory stress. DESIGN: Sixteen healthy infants,
      with a median age of 10 weeks (range: 6-16 weeks), underwent polygraphic
      recording in their usual supine position during one night. The infants were
      successively recorded swaddled and nonswaddled, or vice versa. In both
      conditions, the infants were exposed to white noise of increasing intensity, from
      50 to 100 dB(A), during rapid eye movement sleep, to determine their arousal
      thresholds. RESULTS: Swaddling was associated with increases in the infants'
      sleep efficiency and in the time spent in non-rapid eye movement sleep. When
      swaddled, the infants awakened spontaneously less often. However, significantly
      less-intense auditory stimuli were needed during rapid eye movement sleep to
      induce cortical arousals when swaddled than when not swaddled. CONCLUSIONS:
      Swaddling promotes more-sustained sleep and reduces the frequency of spontaneous
      awakenings, whereas induced cortical arousals are elicited by less-intense
      stimuli. These findings could indicate that, although swaddling favors sleep
      continuity, it is associated with increased responsiveness to environmental
      auditory stress.

PMID- 15867038
TI  - Reduction in red blood cell transfusions among preterm infants: results of a
      randomized trial with an in-line blood gas and chemistry monitor.
AB  - BACKGROUND: Critically ill, extremely premature infants develop anemia because of
      intensive laboratory blood testing and undergo multiple red blood cell (RBC)
      transfusions in the early weeks of life. To date, researchers have had only
      limited success in finding ways to reduce transfusions significantly in this
      patient population. OBJECTIVE: To reduce RBC transfusions for these infants by
      using a point-of-care bedside monitor that returns analyzed blood to the patient.
      DESIGN, SETTING, AND PATIENTS: This was a prospective, 2-center, randomized,
      open, controlled, clinical trial with a 1:1 assignment of extremely low birth
      weight infants (weighing 500-1000 g at birth) to control or monitor groups and
      analysis with the intention-to-treat approach. Predefined RBC transfusion
      criteria were applied uniformly in the 2 groups. INTERVENTIONS: Clinical
      treatment of study subjects with an in-line, ex vivo, bedside monitor that
      withdraws blood through an umbilical artery catheter, analyzes blood gases and
      sodium, potassium, and hematocrit levels, and returns the sample to the patient.
      MAIN OUTCOME MEASURES: The total volume and number of RBC transfusions during the
      first 2 weeks of life and the total volume of blood removed for laboratory
      testing. RESULTS: The trial was terminated prematurely when one center's NICU
      changed its standard method of laboratory testing. In the first 2 weeks of life,
      there was a nonsignificant 17% lower cumulative RBC transfusion volume in the
      monitor group (n = 46), compared with the control group (n = 47). However, data
      from the first week only (the period of greater catheter use) demonstrated a
      significant 33% lower cumulative RBC transfusion volume in the monitor group.
      Cumulative phlebotomy loss was approximately 25% less in the monitor group
      throughout the 2-week study period. There was no difference between groups in
      neonatal mortality, morbidity, and neurodevelopmental outcome rates at 18 to 24
      months. This is the first randomized trial documenting that RBC transfusions
      administered to neonates can by reduced by decreasing laboratory phlebotomy loss.
      CONCLUSIONS: As long as an umbilical artery catheter is available for blood
      sampling with an in-line blood gas and chemistry monitor, significant reductions
      in neonatal RBC transfusions can be achieved. The patients most likely to benefit
      from monitor use are the smallest, most critically ill newborns.

PMID- 15867040
TI  - Relationship between age of ear piercing and keloid formation.
AB  - OBJECTIVE: Keloids occur commonly after trauma to the skin, with ear piercing
      being a well-known inciting event. We surveyed 32 patients with keloids resulting
      from ear piercing, to examine a potential relationship between age of piercing
      and keloid formation. METHODS: A total of 32 consecutive patients completed a
      survey about ear-piercing and keloid formation. Fisher's exact test was used for
      data analysis. RESULTS: Fifty percent (n = 16) of surveyed patients developed a
      keloid after their first piercing. Twenty surveyed patients developed keloids
      with subsequent piercings. Those who had piercings at > or =11 years of age were
      more likely to develop keloids (80%) than were those who had piercings at <11
      years of age (23.5%). CONCLUSIONS: Keloids are more likely to develop when ears
      are pierced after age 11 than before age 11. This observation holds true for
      patients with a family history of keloids. Given the difficulty and cost of
      treating keloids, prevention remains the best approach. Patients with a family
      history of keloids should consider not having their ears pierced. If this is not
      an option, then piercing during early childhood, rather than later childhood, may
      be advisable. Primary care physicians and pediatricians should educate children
      and their parents about the risk of keloid formation.

PMID- 15867041
TI  - Depressive symptoms predict hospitalization for adolescents with type 1 diabetes
      mellitus.
AB  - OBJECTIVE: To examine the role of self-reported depressive symptoms in predicting
      hospitalization for complications of diabetes mellitus over a period of up to 2
      years. STUDY DESIGN: Two hundred thirty-one adolescent outpatients (age range: 11
      18 years) with type 1 diabetes completed the Center for Epidemiological Studies
      Depression Scale, a self-report measure of depressive symptoms. Glycosylated
      hemoglobin levels were also assessed, to account for this known predictor of
      hospitalization. With survival analysis methods, hospitalizations for medical
      complications that occurred up to 2 years after this assessment were recorded.
      RESULTS: After controlling for age, gender, socioeconomic status, and
      glycosylated hemoglobin levels at baseline, the odds ratio for prediction offered
      by Center for Epidemiological Studies Depression Scale scores above the cutoff
      point (12 for boys and 22 for girls) was 2.58 (95% confidence interval: 1.12
      5.98). CONCLUSIONS: Young people with type 1 diabetes who show high levels of
      depressive symptoms are at increased risk for hospitalization for disease
      complications. Interventions aimed at improving their depressive symptoms may
      result in positive health outcomes, as well as improved quality of life.

PMID- 15867042
TI  - Flexible insulin therapy with glargine insulin improved glycemic control and
      reduced severe hypoglycemia among preschool-aged children with type 1 diabetes
      mellitus.
AB  - BACKGROUND AND OBJECTIVES: Insulin replacement regimens now stress the importance
      of administering throughout the day insulin doses that are based on flexible food
      choices and focusing on improved metabolic control. A flexible multiple daily
      insulin (FMDI) regimen (premeal lispro plus bedtime glargine) results in lower
      hemoglobin A1c (HbA1c) levels and fewer hypoglycemic episodes than does a
      multiple daily insulin (MDI) regimen among school-aged children and adolescents
      with type 1 diabetes mellitus (DM). The purpose of this study was to determine
      the feasibility of FMDI therapy for a group of preschool-aged children with type
      1 DM who were transitioned from MDI therapy (premeal lispro plus ultralente
      insulin twice per day), by comparing BMI, total daily insulin requirements, HbA1c
      levels, and episodes of severe hypoglycemia. RESEARCH DESIGN AND METHODS: Data
      were collected over a 2-year period, during quarterly DM clinic visits, from 35
      patients (17 female patients and 18 male patients, 4.8 +/- 1.0 years of age) who
      had received MDI insulin therapy for > or =1 year before being transitioned to a
      FMDI regimen. RESULTS: Although there was no significant change in BMI with FMDI
      therapy (17.1 +/- 1.8 kg/m2 vs 17.0 +/- 1.7 kg/m2), 43% of patients (6 female
      subjects and 9 male subjects) were overweight (BMI of >85th percentile for age)
      both before and after treatment. The total daily insulin requirement (0.67 +/-
      0.13 U/kg per day vs 0.78 +/- 0.14 U/kg per day) and bolus/basal insulin ratio
      (1.1 +/- 0.4 vs 1.9 +/- 0.6) were significantly increased and overall glycemic
      control was improved after transition to FMDI therapy (HbA1c levels: 8.8 +/- 0.9%
      vs 8.3 +/- 0.8%). However, HbA1c levels improved only among normal-weight
      subjects (9.0 +/- 1.0% vs 8.3 +/- 1.0%) and not among overweight subjects (8.7 +/
      0.7% vs 8.4 +/- 0.6%) after FMDI therapy. The overall rate of severe
      hypoglycemia was significantly decreased with the FMDI regimen (25.5 events per
      100 patient-years vs 10.6 events per 100 patient-years) but again only for normal
      weight children (29.7 events per 100 patient-years vs 7.4 events per 100 patient
      years). CONCLUSIONS: The use of FMDI therapy with glargine among preschool-aged
      children with type 1 DM was associated with improved overall glycemic control and
      decreased frequency of severe hypoglycemia. Although our study did not have a
      control group, these findings suggest that FMDI regimens may be a feasible
      therapeutic alternative to MDI treatment for preschool-aged children with type 1
      DM. However, excess body weight status appeared to preclude a desirable
      therapeutic response in this group of patients.

PMID- 15867043
TI  - Vitamin K status among children with cystic fibrosis and its relationship to bone
      mineral density and bone turnover.
AB  - OBJECTIVE: The aim of this study was to assess vitamin K status in an unselected
      population of children with cystic fibrosis (CF) and to investigate any vitamin K
      effect on bone turnover and bone mineral status. METHODS: Children > or =5 years
      of age who were attending the CF unit were invited to enter the study. Fasting
      blood samples were analyzed for levels of vitamin K1 and prothrombin produced in
      vitamin K absence; total, undercarboxylated, and carboxylated osteocalcin (OC);
      and bone-specific alkaline phosphatase and procollagen I carboxy-terminal
      propeptide (bone formation markers). Levels of N-telopeptide and free
      pyridinoline and deoxypyridinoline (bone breakdown products) were measured in
      urine samples. Bone mineral density and bone mineral content were measured at the
      lumbar spine and for the total body with a GE Lunar Prodigy densitometer.
      Statistical analyses were performed with Minitab version 9.1. RESULTS: One
      hundred six children entered the study. Sixty-five of 93 children (70%) from whom
      blood samples were obtained showed suboptimal vitamin K status, on the basis of
      low serum vitamin K1 levels, increased prothrombin produced in vitamin K absence
      levels, or both abnormalities. Vitamin K1 levels showed a significant negative
      correlation with undercarboxylated OC levels but showed no significant
      correlation with any marker of bone turnover or measurement of bone mineral
      status. Undercarboxylated OC levels were correlated significantly with bone
      turnover markers, which themselves showed a significant negative correlation with
      measurements of bone mineral density and content. There were no significant
      correlations between carboxylated or undercarboxylated OC levels and bone density
      measurements. CONCLUSIONS: Vitamin K1 deficiency is common among children with
      CF, and routine supplements should be considered. Through its role in the
      carboxylation of OC, vitamin K deficiency may be associated with an uncoupling of
      the balance between bone resorption and bone formation. A cause-effect
      relationship between vitamin K deficiency and low bone mass has not been proved.

PMID- 15867044
TI  - Use of cholecystokinin-octapeptide for the prevention of parenteral nutrition
      associated cholestasis.
AB  - OBJECTIVE: To determine whether cholecystokinin-octapeptide (CCK-OP) would
      prevent or ameliorate parenteral nutrition-associated cholestasis (PNAC) among
      high-risk neonates treated with total parenteral nutrition. STUDY DESIGN: This
      was a multicenter, double-blind, randomized, controlled trial conducted between
      1996 and 2001. PATIENTS: Neonates at risk for the development of PNAC included
      very low birth weight neonates and those with major surgical conditions involving
      the gastrointestinal tract. SETTING: Tertiary care hospitals. INTERVENTION:
      Patients were randomized to receive CCK-OP (0.04 mug/kg per dose, twice daily) or
      placebo. Eligible infants were all <30 days of age. Patients were enrolled within
      2 weeks after birth or within 7 days after surgery. OUTCOME MEASURES: The primary
      outcome measure was conjugated bilirubin (CB) levels, which were measured weekly.
      Secondary outcome measures included incidence of sepsis, times to achieve 50% and
      100% of energy intake through the enteral route, number of ICU and hospital days,
      mortality rate, and incidences of biliary sludge and cholelithiasis. RESULTS: A
      total of 243 neonates were enrolled in the study. CCK-OP administration did not
      significantly affect CB levels (1.76 +/- 3.14 and 1.93 +/- 3.31 mg/dL for CCK-OP
      and placebo groups, respectively; mean +/- SD). Secondary outcome measures also
      were not significantly affected by the study drug. CONCLUSIONS: Use of CCK-OP
      failed to reduce significantly the incidence of PNAC or levels of CB. CCK-OP had
      no effect on other secondary measures and should not be recommended for the
      prevention of PNAC.

PMID- 15867045
TI  - Can tissue transglutaminase antibody titers replace small-bowel biopsy to
      diagnose celiac disease in select pediatric populations?
AB  - OBJECTIVES: The use of screening tests for celiac disease has increased the
      number of patients referred for evaluation. We proposed that the subgroup of
      patients with very high tissue transglutaminase antibody (TTG) titers is positive
      for celiac disease and a small-bowel biopsy is not necessary to make the
      diagnosis. A gluten-free diet should be attempted and, if the patient's symptoms
      do not improve, then a biopsy should be performed to confirm the diagnosis.
      METHODS: A chart review of data for 103 patients who underwent both TTG testing
      and a small-bowel biopsy was performed. We examined the impact of using TTG
      values of >100 U and <20 U as cutoff values and suggested performing biopsies for
      patients with TTG values of 20 to 100 U, as is current practice. RESULTS: Fifty
      eight of 103 patients demonstrated positive biopsy results. Forty-nine of 103
      patients had TTG levels of >100 U, with 48 of 49 exhibiting positive biopsy
      results. Only 7 of 16 patients with TTG values of 20 to 100 U exhibited positive
      biopsy results. Three patients with TTG levels of <20 U had positive biopsies; 2
      were IgA negative and 1 had a duodenal ulcer. With the cutoff values of >100 U
      and <20 U with known IgA status, the sensitivity was 0.980 (48 of 49 cases) and
      the specificity was 0.972 (35 of 36 cases). An incremental cost analysis found
      that this proposal could potentially decrease the costs of investigation and
      diagnosis by almost 30%. CONCLUSIONS: When the cutoff values were changed to >100
      and <20 U and IgA levels were verified, the sensitivity and specificity were very
      high. Patients with mid-range TTG values (20-100 U) or values of <20 U with
      negative IgA status should continue to undergo biopsies for diagnosis of celiac
      disease.

PMID- 15867046
TI  - Amino-terminal pro-brain-type natriuretic peptide: heart or lung disease in
      pediatric respiratory distress?
AB  - OBJECTIVES: The aim of this study was to determine whether plasma levels of amino
      terminal pro-brain natriuretic peptide (N-BNP) could differentiate between heart
      failure and lung disease among infants with acute respiratory distress. In
      addition, our aim was to determine whether plasma levels of N-BNP could be used
      to monitor the effects of treatment among infants with heart failure. METHODS:
      Infants (age range: 1-36 months; median age: 10 months) who presented with
      respiratory distress underwent physical examination, plasma N-BNP measurement,
      and echocardiography within 24 hours after admission. Seventeen infants were
      finally diagnosed with acute heart failure and 18 with acute lung disease.
      Thirteen healthy infants served as a control group. RESULTS: Plasma N-BNP levels
      were significantly higher for the infants with heart failure (median: 18452
      pg/mL; range: 5375-99700 pg/mL) than for the infants with lung disease (median:
      311 pg/mL; range: 76-1341 pg/mL). Among the infants with heart failure, there was
      a significant difference in plasma N-BNP levels before and after congestive heart
      failure treatment. CONCLUSION: Among infants with respiratory distress, plasma N
      BNP measurements can differentiate between acute heart failure and lung disease
      and can be used to monitor the effects of treatment for infants with heart
      failure.

PMID- 15867047
TI  - Morphine, hypotension, and adverse outcomes among preterm neonates: who's to
      blame? Secondary results from the NEOPAIN trial.
AB  - OBJECTIVES: Hypotension occurs commonly among preterm neonates, but its cause and
      consequences remain unclear. Secondary data analyses from the NEOPAIN trial
      identified the clinical factors associated with hypotension and examined the
      contributions of morphine treatment or hypotension to severe intraventricular
      hemorrhage (IVH) (grades 3 and 4), any IVH (grades 1-4), or death. METHODS: In
      the NEOPAIN trial, 898 ventilated neonates between 23 and 32 weeks of gestation
      were enrolled, with equal numbers randomized to receive masked morphine or
      placebo infusions. Additional doses of open-label morphine were administered as
      necessary by medical staff members. IVH was diagnosed with centralized readings
      of early and late cranial ultrasonograms. Hypotension was assessed before study
      drug infusion, during the loading dose, and at 24 and 72 hours during study drug
      infusion. Logistic regression analyses with stepdown elimination identified the
      predictor factors associated with the hypotension, severe IVH, any IVH, or death
      outcomes at each time point. RESULTS: Hypotension was associated with 23 to 26
      weeks of gestation, morphine infusions, severity of illness, additional morphine
      doses, and prior hypotension. Severe IVH was associated with shorter gestation,
      higher Clinical Risk Index for Babies scores, no prenatal steroids, pulmonary
      hemorrhage, hypotension before the loading dose, and morphine doses before
      intubation and at 25 to 72 hours. Neonatal deaths were associated with 23 to 26
      weeks of gestation, higher Clinical Risk Index for Babies scores, pulmonary
      hemorrhage, patent ductus arteriosus, thrombocytopenia, and hypotension before
      the loading dose. Morphine infusions were not a significant factor in logistic
      models for severe IVH, any IVH, or death. CONCLUSIONS: Preemptive morphine
      infusions, additional morphine, and lower gestational age were associated with
      hypotension among preterm neonates. Severe IVH, any IVH, and death were
      associated with preexisting hypotension, but morphine therapy did not contribute
      to these outcomes. Morphine infusions, although they cause hypotension, can be
      used safely for most preterm neonates but should be used cautiously for 23- to 26
      week neonates and those with preexisting hypotension.

PMID- 15867048
TI  - The Oxford-Durham study: a randomized, controlled trial of dietary
      supplementation with fatty acids in children with developmental coordination
      disorder.
AB  - BACKGROUND: Developmental coordination disorder (DCD) affects approximately 5% of
      school-aged children. In addition to the core deficits in motor function, this
      condition is associated commonly with difficulties in learning, behavior, and
      psychosocial adjustment that persist into adulthood. Mounting evidence suggests
      that a relative lack of certain polyunsaturated fatty acids may contribute to
      related neurodevelopmental and psychiatric disorders such as dyslexia and
      attention-deficit/hyperactivity disorder. Given the current lack of effective,
      evidence-based treatment options for DCD, the use of fatty acid supplements
      merits investigation. METHODS: A randomized, controlled trial of dietary
      supplementation with omega-3 and omega-6 fatty acids, compared with placebo, was
      conducted with 117 children with DCD (5-12 years of age). Treatment for 3 months
      in parallel groups was followed by a 1-way crossover from placebo to active
      treatment for an additional 3 months. RESULTS: No effect of treatment on motor
      skills was apparent, but significant improvements for active treatment versus
      placebo were found in reading, spelling, and behavior over 3 months of treatment
      in parallel groups. After the crossover, similar changes were seen in the placebo
      active group, whereas children continuing with active treatment maintained or
      improved their progress. CONCLUSIONS: Fatty acid supplementation may offer a safe
      efficacious treatment option for educational and behavioral problems among
      children with DCD. Additional work is needed to investigate whether our inability
      to detect any improvement in motor skills reflects the measures used and to
      assess the durability of treatment effects on behavior and academic progress.

PMID- 15867049
TI  - Effect of infant feeding on the risk of obesity across the life course: a
      quantitative review of published evidence.
AB  - OBJECTIVE: To examine the influence of initial infant feeding on obesity in later
      life. METHODS: A systematic review of published studies investigating the
      association between infant feeding and a measure of obesity was performed with
      Medline (1966 onward) and Embase (1980 onward) databases, supplemented with
      manual searches. Data extraction was conducted by 2 authors. Analyses were based
      on odds ratios of obesity among initially breastfed subjects, compared with
      formula-fed subjects, pooled with fixed-effects models. RESULTS: Sixty-one
      studies reported on the relationship of infant feeding to a measure of obesity in
      later life; of these, 28 (298900 subjects) provided odds ratio estimates. In
      these studies, breastfeeding was associated with a reduced risk of obesity,
      compared with formula feeding (odds ratio: 0.87; 95% confidence interval [CI]:
      0.85-0.89). The inverse association between breastfeeding and obesity was
      particularly strong in 11 small studies of <500 subjects (odds ratio: 0.43; 95%
      CI: 0.33-0.55) but was still apparent in larger studies of > or =500 subjects
      (odds ratio: 0.88; 95% CI: 0.85-0.90). In 6 studies that adjusted for all 3 major
      potential confounding factors (parental obesity, maternal smoking, and social
      class), the inverse association was reduced markedly (from an odds ratio of 0.86
      to 0.93) but not abolished. A sensitivity analysis examining the potential impact
      of the results of 33 published studies (12505 subjects) that did not provide odds
      ratios (mostly reporting no relationship between breastfeeding and obesity)
      showed little effect on the results. CONCLUSIONS: Initial breastfeeding protects
      against obesity in later life. However, a further review including large
      unpublished studies exploring the effect of confounding factors in more detail is
      needed.

PMID- 15867050
TI  - Quality of evidence-based pediatric guidelines.
AB  - OBJECTIVE: To identify evidence-based pediatric guidelines and to assess their
      quality. METHODS: We searched Medline, Embase, and relevant Web sites of
      guideline development programs and national pediatric societies to identify
      evidence-based pediatric guidelines. A list with titles of identified guidelines
      was sent to 51 leading pediatricians in the Netherlands, who were asked to select
      the 5 most urgent topics for guideline development. Three pediatrician reviewers
      appraised the available guidelines on the 10 most frequently mentioned topics
      with the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument.
      RESULTS: A total of 215 evidence-based pediatric guidelines were identified; of
      these, 17 guidelines on the 10 most frequently mentioned topics were appraised.
      The AGREE instrument rates guidelines among 6 domains. For the scope and purpose
      domain, the mean score was 84% of the maximal mark. For stakeholder involvement,
      the mean score was 42%, with 12 guidelines (71%) scoring <50%. For rigor of
      development, the mean score was 54%, with 5 guidelines (29%) scoring <50%. For
      clarity and presentation, the mean score was 78%, with 4 guidelines (24%) scoring
      <50%. For applicability and editorial independence, performance was poor, with
      mean scores of 19% and 40%, respectively. Low scores were partly attributable to
      poor reporting. After considering all domain scores, the reviewers recommended 14
      of 17 guidelines (82%) to be used in local practice. CONCLUSIONS: The current
      volume of pediatric guidelines categorized as evidence based in popular databases
      is large. Overall, these guidelines scored well, compared with other studies on
      guideline quality in fields outside pediatrics, when assessed for quality with
      the AGREE instrument. This holds especially for guidelines published or endorsed
      by the American Academy of Pediatrics or registered in the National Guideline
      Clearinghouse.

PMID- 15867051
TI  - Executive summary of the workshop on the border of viability.
AB  - One of the most complex areas in perinatal-neonatal medicine remains the care of
      the mother delivering a newborn infant at the border of viability, referred to as
      "periviable" gestation. To address the knowledge gaps that preclude optimal,
      evidence-based care in this critical field of perinatal medicine, the National
      Institute of Child Health and Human Development organized a workshop in March
      2004. This article provides a summary of the discussions, focusing on major
      knowledge gaps and prioritized suggestions for studies in this area.

PMID- 15867052
TI  - 2004 Job Lewis Smith acceptance address.

PMID- 15867053
TI  - Impact of serum bilirubin on human diseases.

PMID- 15867054
TI  - Underwater births.

PMID- 15867055
TI  - Lemierre's syndrome: the controversy of anticoagulation.

PMID- 15867056
TI  - Resuscitation decisions for "fetal infants".

PMID- 15867057
TI  - Morphine, hypotension, and intraventricular hemorrhage in the ventilated
      premature infant.

PMID- 15867058
TI  - Immersion scald burns and the ability of young children to climb into a bathtub.
AB  - INTRODUCTION: Immersion scald burns in children are often suspicious for neglect
      or abuse. The history that a child climbed into a tub previously filled with hot
      water by the parent is common. The child's ability to climb into such a tub is a
      major factor in determining the reliability of the history. METHODS: A standard
      bathtub was installed in an examination room at a pediatric clinic in a
      children's hospital. Foam mats were placed in and outside of the tub. Toy boats
      were placed in the back of the tub. Children were selected if they were between
      10 and 18 months of age, born at term, and had no past or present medical
      condition that could be expected to have affected their fine or gross motor or
      central nervous system development and had a normal Denver Developmental
      Screening Test within the past 3 months. The parent placed the child in a
      standing position with the child holding onto the front of the tub. Parents
      encouraged the child to climb into the tub and get the toys. The child's efforts
      were videotaped. Children were allowed 5 minutes to climb, depending on their
      attention span and tolerance. RESULTS: Of 176 children in the study, 62 (35%)
      climbed into the tub. One fourth climbed in head first, and the rest climbed in
      sideways. CONCLUSIONS: Our study may have underestimated children's climbing
      abilities because of the absence of a shower curtain to help with balance and the
      distracting presence of strangers. The diagnosis of abuse is in part based on a
      described mechanism being inconsistent with the observed pattern of injury. This
      has severe repercussions for the child and his or her family. Our study brings
      into question previously held beliefs that these injuries could only be sustained
      by direct immersion.

PMID- 15867059
TI  - The epidemiology of pertussis: a comparison of the epidemiology of the disease
      pertussis with the epidemiology of Bordetella pertussis infection.
AB  - In the prevaccine era pertussis epidemics followed a cyclic pattern, with peaks
      every 2 to 5 years. With the marked reduction of pertussis by vaccination, the
      same cyclic pattern still occurs. Studies relating to reported pertussis and
      Bordetella pertussis infection have been reviewed and analyzed. The increase in
      reported pertussis over the last 2 decades is mainly due to a greater awareness
      of pertussis and perhaps to the use of several less efficacious vaccines. Studies
      of prolonged cough illnesses in adolescents and adults reveal that 13% to 20% are
      a result of B pertussis infection. Serologic studies suggest that the rate of B
      pertussis infection in adolescents and adults is approximately 2.0% per year. The
      rate of cough illnesses (pertussis) caused by B pertussis infection in
      adolescents and adults is between 370 and 1500 per 100,000 population. These data
      suggest that there are between approximately 800,000 and 3.3 million cases per
      year in the United States. The coming availability of adolescent- and adult
      formulated diphtheria and tetanus toxoids and acellular pertussis vaccines for
      adolescents and adults and their widespread use should reduce the reservoir of B
      pertussis disease. It is suggested that a universal program of adolescent and
      adult boosters would decrease the circulation of B pertussis in these age groups
      and possibly could lead to the elimination of the organism from the population.

PMID- 15867060
TI  - Responding to parental refusals of immunization of children.
AB  - The American Academy of Pediatrics strongly endorses universal immunization.
      However, for childhood immunization programs to be successful, parents must
      comply with immunization recommendations. The problem of parental refusal of
      immunization for children is an important one for pediatricians. The goal of this
      report is to assist pediatricians in understanding the reasons parents may have
      for refusing to immunize their children, review the limited circumstances under
      which parental refusals should be referred to child protective services agencies
      or public health authorities, and provide practical guidance to assist the
      pediatrician faced with a parent who is reluctant to allow immunization of his or
      her child.

PMID- 15867061
TI  - Death of a child in the emergency department.
AB  - Of the estimated 40000 American children < or =14 years old who die each year,
      approximately 20% die or are pronounced dead in outpatient sites, primarily the
      emergency department (ED). The ED is distinguishable from other sites at which
      children die, because the death is often sudden, unexpected, and without a
      previously established physician-patient care relationship. Despite these
      difficult circumstances and potentially limited professional experience with the
      death of a child, the emergency physician must be prepared to respond to the
      emotional, cultural, procedural, and legal issues that are an inevitable part of
      caring for ill and injured children who die. All of this must be accomplished
      while supporting a grieving family. There is also a responsibility to inform the
      child's pediatrician of the death, who in turn also must be prepared to counsel
      and support bereaved families. The American Academy of Pediatrics and American
      College of Emergency Physicians collaborated on the joint policy statement,
      "Death of a Child in the Emergency Department," agreeing on recommendations on
      the principles of care after the death of a child in the ED. This technical
      report provides the background information, consensus opinion, and evidence,
      where available, used to support the recommendations found in the policy
      statement. Important among these are the pediatrician's role as an advocate to
      advise in the formulation of ED policy and procedure that facilitate
      identification and management of medical examiners' cases, identification and
      reporting of child maltreatment, requests for postmortem examinations, and
      procurement of organ donations.

PMID- 15867062
TI  - Optimal timing and dosing intervals of palivizumab in premature neonates: still
      some work to do.

PMID- 15867064
TI  - Rapid feeding volume advancements: uncertainty about the effect on necrotizing
      enterocolitis incidence.

PMID- 15867067
TI  - Improvement of glucose homeostasis after weight loss in obese children.

PMID- 15867068
TI  - Possible confounding factors in an oral probiotics trial: breast milk.

PMID- 15867069
TI  - Thoughts on the American Academy of Pediatrics/American Academy of Family
      Physicians clinical practice guideline on acute otitis media: a different
      perspective.

PMID- 15867073
TI  - Misinterpretation of liver-function tests and West Nile virus infection in
      children.

PMID- 15867074
TI  - Weighing statistical certainty against ethical, clinical, and biologic
      expediency: the contributions of the Watterberg trial tip the scales in the right
      direction.

PMID- 15867075
TI  - Use of risperidone in developmentally disabled children.

PMID- 15867077
TI  - Characteristics of ice hockey-related injuries treated in US emergency
      departments, 2001-2002.

PMID- 15867079
TI  - Health care transition.

PMID- 15867081
TI  - More about the Ross Mothers Survey.

PMID- 15867083
TI  - Russian roulette: final 2.

PMID- 15867085
TI  - Nuvo lotion and the future of head-lice treatment.

PMID- 15867086
TI  - Benzocaine: not dangerous enough?

PMID- 15867087
TI  - Limits of the Health Plan Employer Data Information Set (HEDIS) criteria in
      determining asthma severity for children, applied to an impoverished, urban
      population.

PMID- 15867088
TI  - Research on human subjects in the JEM.

PMID- 15867089
TI  - Blocking IL-1 in systemic inflammation.
AB  - A growing number of systemic inflammatory diseases characterized in part by
      recurrent fevers, leukocytosis, anemia, and elevated acute phase proteins are
      linked to interleukin (IL)-1 activity since rapid and sustained resolution is
      observed upon specific blockade of IL-1 receptors. Rapid resolution of systemic
      and local inflammation is now also reported in systemic onset juvenile idiopathic
      arthritis (SoJIA). Loss of control of the secretion of IL-1beta might be a common
      mechanism explaining the aberrant activity of IL-1 in these diseases.

PMID- 15867090
TI  - T cell lineage choice and differentiation in the absence of the RNase III enzyme
      Dicer.
AB  - The ribonuclease III enzyme Dicer is essential for the processing of micro-RNAs
      (miRNAs) and small interfering RNAs (siRNAs) from double-stranded RNA precursors.
      miRNAs and siRNAs regulate chromatin structure, gene transcription, mRNA
      stability, and translation in a wide range of organisms. To provide a model
      system to explore the role of Dicer-generated RNAs in the differentiation of
      mammalian cells in vivo, we have generated a conditional Dicer allele. Deletion
      of Dicer at an early stage of T cell development compromised the survival of
      alphabeta lineage cells, whereas the numbers of gammadelta-expressing thymocytes
      were not affected. In developing thymocytes, Dicer was not required for the
      maintenance of transcriptional silencing at pericentromeric satellite sequences
      (constitutive heterochromatin), the maintenance of DNA methylation and X
      chromosome inactivation in female cells (facultative heterochromatin), and the
      stable shutdown of a developmentally regulated gene (developmentally regulated
      gene silencing). Most remarkably, given that one third of mammalian mRNAs are
      putative miRNA targets, Dicer seems to be dispensable for CD4/8 lineage
      commitment, a process in which epigenetic regulation of lineage choice has been
      well documented. Thus, although Dicer seems to be critical for the development of
      the early embryo, it may have limited impact on the implementation of some
      lineage-specific gene expression programs.

PMID- 15867091
TI  - Differential requirement for OBF-1 during antibody-secreting cell
      differentiation.
AB  - Resting B cells can be cultured to induce antibody-secreting cell (ASC)
      differentiation in vitro. A quantitative analysis of cell behavior during such a
      culture allows the influences of different stimuli and gene products to be
      measured. The application of this analytical system revealed that the OBF-1
      transcriptional coactivator, whose loss impairs antibody production in vivo, has
      two effects on ASC development. Although OBF-1 represses early T cell-dependent
      (TD) differentiation, it is also critical for the completion of the final stages
      of ASC development. Under these conditions, the loss of OBF-1 blocks the genetic
      program of ASC differentiation so that Blimp-1/prdm1 induction fails, and bcl-6,
      Pax5, and AID are not repressed as in control ASC. Retroviral complementation
      confirmed that OBF-1 was the critical entity. Surprisingly, when cells were
      cultured in lipopolysaccharide to mimic T cell-independent conditions, OBF-1-null
      B cells differentiated normally to ASC. In the OBF-1(-/-) ASC generated under
      either culture regimen, antibody production was normal or only modestly reduced,
      revealing that Ig genes are not directly dependent on OBF-1 for their expression.
      The differential requirement for OBF-1 in TD ASC generation was confirmed in
      vivo. These studies define a new regulatory role for OBF-1 in determining the
      cell-autonomous capacity of B cells to undergo terminal differentiation in
      response to different immunological signals.

PMID- 15867092
TI  - Transplantation of a multipotent cell population from human adipose tissue
      induces dystrophin expression in the immunocompetent mdx mouse.
AB  - Here, we report the isolation of a human multipotent adipose-derived stem (hMADS)
      cell population from adipose tissue of young donors. hMADS cells display normal
      karyotype; have active telomerase; proliferate >200 population doublings; and
      differentiate into adipocytes, osteoblasts, and myoblasts. Flow cytometry
      analysis indicates that hMADS cells are CD44+, CD49b+, CD105+, CD90+, CD13+, Stro
      1(-), CD34-, CD15-, CD117-, Flk-1(-), gly-A(-), CD133-, HLA-DR(-), and HLA
      I(low). Transplantation of hMADS cells into the mdx mouse, an animal model of
      Duchenne muscular dystrophy, results in substantial expression of human
      dystrophin in the injected tibialis anterior and the adjacent gastrocnemius
      muscle. Long-term engraftment of hMADS cells takes place in nonimmunocompromised
      animals. Based on the small amounts of an easily available tissue source, their
      strong capacity for expansion ex vivo, their multipotent differentiation, and
      their immune-privileged behavior, our results suggest that hMADS cells will be an
      important tool for muscle cell-mediated therapy.

PMID- 15867093
TI  - Antigenic conservation and immunogenicity of the HIV coreceptor binding site.
AB  - Immunogenic, broadly reactive epitopes of the HIV-1 envelope glycoprotein could
      serve as important targets of the adaptive humoral immune response in natural
      infection and, potentially, as components of an acquired immune deficiency
      syndrome vaccine. However, variability in exposed epitopes and a combination of
      highly effective envelope-cloaking strategies have made the identification of
      such epitopes problematic. Here, we show that the chemokine coreceptor binding
      site of HIV-1 from clade A, B, C, D, F, G, and H and circulating recombinant form
      (CRF)01, CRF02, and CRF11, elicits high titers of CD4-induced (CD4i) antibody
      during natural human infection and that these antibodies bind and neutralize
      viruses as divergent as HIV-2 in the presence of soluble CD4 (sCD4). 178 out of
      189 (94%) HIV-1-infected patients had CD4i antibodies that neutralized sCD4
      pretreated HIV-2 in titers (50% inhibitory concentration) as high as 1:143,000.
      CD4i monoclonal antibodies elicited by HIV-1 infection also neutralized HIV-2
      pretreated with sCD4, and polyclonal antibodies from HIV-1-infected humans
      competed specifically with such monoclonal antibodies for binding. In vivo,
      variants of HIV-1 with spontaneously exposed coreceptor binding surfaces were
      detected in human plasma; these viruses were neutralized directly by CD4i
      antibodies. Despite remarkable evolutionary diversity among primate lentiviruses,
      functional constraints on receptor binding create opportunities for broad humoral
      immune recognition, which in turn serves to constrain the viral quasispecies.

PMID- 15867094
TI  - A requirement for CD45 distinguishes Ly49D-mediated cytokine and chemokine
      production from killing in primary natural killer cells.
AB  - Engagement of receptors on the surface of natural killer (NK) cells initiates a
      biochemical cascade ultimately triggering cytokine production and cytotoxicity,
      although the interrelationship between these two outcomes is currently unclear.
      In this study we investigate the role of the cell surface phosphatase CD45 in NK
      cell development and intracellular signaling from activating receptors.
      Stimulation via the major histocompatibility complex I-binding receptor, Ly49D on
      CD45(-/-) primary NK cells resulted in the activation of phosphoinositide-3
      kinase and normal cytotoxicity but failed to elicit a range of cytokines and
      chemokines. This blockage is associated with impaired phosphorylation of Syk,
      Vav1, JNK, and p38, which mimics data obtained using inhibitors of the src-family
      kinases (SFK). These data, supported by analogous findings after CD16 and NKG2D
      stimulation of CD45(-/-) primary NK cells, place CD45 upstream of SFK in NK cells
      after stimulation via immunoreceptor tyrosine-based activation motif-containing
      receptors. Thus we identify CD45 as a pivotal enzyme in eliciting a precise
      subset of NK cell responses.

PMID- 15867095
TI  - Intricate targeting of immunoglobulin somatic hypermutation maximizes the
      efficiency of affinity maturation.
AB  - It is believed that immunoglobulin-variable region gene (IgV) somatic
      hypermutation (SHM) is initiated by activation-induced cytidine deaminase (AID)
      upon deamination of cytidine to deoxyuracil. Patch-excision repair of these
      lesions involving error prone DNA polymerases such as poleta causes mutations at
      all base positions. If not repaired, the deaminated nucleotides on the coding and
      noncoding strands result in C-to-T and G-to-A exchanges, respectively. Herein it
      is reported that IgV gene evolution has been considerably influenced by the need
      to accommodate extensive C deaminations and the resulting accumulation of C-to-T
      and G-to-A exchanges. Although seemingly counterintuitive, the precise placement
      of C and G nucleotides causes most C-to-T and G-to-A mutations to be silent or
      conservative. We hypothesize that without intricate positioning of C and G
      nucleotides the efficiency of affinity maturation would be significantly reduced
      due to a dominance of replacements caused by C and G transition mutations. The
      complexity of these evolved biases in codon use are compounded by the precise
      concomitant hotspot/coldspot targeting of AID activity and Poleta errors to
      maximize SHM in the CDRs and minimize mutations in the FWRs.

PMID- 15867096
TI  - PU.1 regulates the commitment of adult hematopoietic progenitors and restricts
      granulopoiesis.
AB  - Although the transcription factor PU.1 is essential for fetal lymphomyelopoiesis,
      we unexpectedly found that elimination of the gene in adult mice allowed
      disturbed hematopoiesis, dominated by granulocyte production. Impaired production
      of lymphocytes was evident in PU.1-deficient bone marrow (BM), but myelocytes and
      clonogenic granulocytic progenitors that are responsive to granulocyte colony
      stimulating factor or interleukin-3 increased dramatically. No identifiable
      common lymphoid or myeloid progenitor populations were discernable by flow
      cytometry; however, clonogenic assays suggested an overall increased frequency of
      blast colony-forming cells and BM chimeras revealed existence of long-term self
      renewing PU.1-deficient cells that required PU.1 for lymphoid, but not
      granulocyte, generation. PU.1 deletion in granulocyte-macrophage progenitors, but
      not in common myeloid progenitors, resulted in excess granulocyte production;
      this suggested specific roles of PU.1 at different stages of myeloid development.
      These findings emphasize the distinct nature of adult hematopoiesis and reveal
      that PU.1 regulates the specification of the multipotent lymphoid and myeloid
      compartments and restrains, rather than promotes, granulopoiesis.

PMID- 15867098
TI  - Gonadotropin-releasing hormone agonists in the treatment of prostate cancer.
AB  - In 1979, the first prostate cancer patient was treated with a GnRH agonist at the
      Laval University Medical Center in Quebec City, Canada, thus rapidly leading to
      the worldwide replacement of surgical castration and high doses of estrogens. The
      discovery of medical castration with GnRH agonists was soon followed by
      fundamental changes in the endocrine therapy of prostate cancer. Most
      importantly, the excellent tolerance accompanying the treatment with GnRH
      agonists has been a key factor that permitted a series of studies demonstrating a
      major reduction in the death rate from prostate cancer ranging from 31 to 87% at
      5 yr of follow-up in patients with localized or locally advanced prostate cancer.
      In fact, a one third reduction in prostate cancer deaths has been calculated in
      the metaanalysis of all available studies. The general acceptance of this
      discovery by patients and physicians is illustrated by world sales above 3.0
      billion U.S. dollars in 2003. Although extremely efficient in achieving complete
      medical castration and well tolerated, with no other side effects than the
      expected hypoandrogenicity, GnRH agonists should not be administered alone. In
      fact, shortly after discovery of the castration effects of GnRH agonists, we
      observed that approximately 50% of androgens remain in the prostate after
      castration, thus leading to the recognition of the role of adrenal
      dehydroepiandrosterone as an important source of the androgens synthesized
      locally in the prostate and in many peripheral target tissues. We therefore
      developed combined androgen blockade (CAB), whereby the androgens of both
      testicular and adrenal origins are blocked simultaneously at start of treatment
      with the combination of a GnRH agonist to block the testis and a pure
      antiandrogen to block the action of the androgens produced locally. CAB, first
      used in advanced metastatic disease, has been the first treatment shown to
      prolong life in prostate cancer. Most interestingly, in 2002, we made the
      observation that CAB alone given continuously for 6.5 yr or more leads to cure of
      the disease in at least 90% of cases, thus suggesting that androgen blockade
      combining a GnRH agonist and a pure antiandrogen could well be the most efficient
      treatment of localized prostate cancer, and thus offering the possibility of
      practically eliminating death from prostate cancer.

PMID- 15867097
TI  - Sustained expansion of NKT cells and antigen-specific T cells after injection of
      alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients.
AB  - Natural killer T (NKT) cells are distinct glycolipid reactive innate lymphocytes
      that are implicated in the resistance to pathogens and tumors. Earlier attempts
      to mobilize NKT cells, specifically, in vivo in humans met with limited success.
      Here, we evaluated intravenous injection of monocyte-derived mature DCs that were
      loaded with a synthetic NKT cell ligand, alpha-galactosyl-ceramide (alpha-GalCer;
      KRN-7000) in five patients who had advanced cancer. Injection of alpha-GalCer
      pulsed, but not unpulsed, dendritic cells (DCs) led to >100-fold expansion of
      several subsets of NKT cells in all patients; these could be detected for up to 6
      mo after vaccination. NKT activation was associated with an increase in serum
      levels of interleukin-12 p40 and IFN-gamma inducible protein-10. In addition,
      there was an increase in memory CD8+ T cells specific for cytomegalovirus in vivo
      in response to alpha-GalCer-loaded DCs, but not unpulsed DCs. These data
      demonstrate the feasibility of sustained expansion of NKT cells in vivo in
      humans, including patients who have advanced cancer, and suggest that NKT
      activation might help to boost adaptive T cell immunity in vivo.

PMID- 15867099
TI  - A clinical lesson at the Salpetriere.

PMID- 15867100
TI  - Strategy for investigating interactions between measured genes and measured
      environments.
AB  - The purpose of this article is to promote research that tests hypotheses of
      measured gene-environment interaction (GxE). A GxE occurs when the effect of
      exposure to an environmental pathogen on health is conditional on a person's
      genotype (or conversely, when environmental experience moderates genes' effects
      on health). Gene-environment interactions were thought to be rare in psychiatry,
      but empirical findings of measured GxEs are now emerging. However, the current
      high level of curiosity about GxE is accompanied by uncertainty about the
      feasibility of GxE research and by pragmatic questions about how to carry out
      good GxE studies. First, we summarize emerging evidence about GxE in psychiatric
      disorders. Second, we describe 7 strategic steps that may be used to organize
      further hypothesis-driven studies of GxE. Third, we explain the potential
      benefits of the measured-GxE approach for basic neuroscience and for gene
      hunting. We suggest that in psychiatric genetics, ignoring nurture handicaps the
      field's capacity to make new discoveries about nature.

PMID- 15867101
TI  - Reduced parahippocampal connectivity produces schizophrenia-like memory deficits
      in simulated neural circuits with reduced parahippocampal connectivity.
AB  - CONTEXT: Episodic memory impairments are well characterized in schizophrenia, but
      their neural origin is unclear. OBJECTIVE: To determine whether the episodic
      memory impairments in schizophrenia may originate from reduced parahippocampal
      connectivity. DESIGN: Experimental in silico model. SETTING: Department of
      Psychology, University of Amsterdam, Amsterdam, the Netherlands. INTERVENTIONS: A
      new, in silico medial temporal lobe model that simulates normal performance on a
      variety of episodic memory tasks was devised. The effects of reducing
      parahippocampal connectivity in the model (from perirhinal and parahippocampal
      cortex to entorhinal cortex and from entorhinal cortex to hippocampus) were
      evaluated and compared with findings in schizophrenic patients. Alternative in
      silico neuropathologies, increased noise and loss of hippocampal neurons, were
      also evaluated. RESULTS: In the model, parahippocampal processing subserves
      integration of different cortical inputs to the hippocampus and feature
      extraction during recall. Reduced connectivity in this area resulted in a pattern
      of deficits that closely mimicked the impairments in schizophrenia, including a
      mild recognition impairment and a more severe impairment in free recall.
      Furthermore, the schizophrenic model was not differentially sensitive to
      interference, also consistent with behavioral data. Notably, neither increased
      noise levels nor a reduction of hippocampal nodes in the model reproduced this
      characteristic memory profile. CONCLUSIONS: Taken together, these findings
      highlight the importance of parahippocampal neuropathology in schizophrenia,
      demonstrating that reduced connectivity in this region may underlie episodic
      memory problems associated with the disorder.

PMID- 15867102
TI  - Early-stage visual processing and cortical amplification deficits in
      schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia show deficits in early-stage visual
      processing, potentially reflecting dysfunction of the magnocellular visual
      pathway. The magnocellular system operates normally in a nonlinear amplification
      mode mediated by glutamatergic (N-methyl-D-aspartate) receptors. Investigating
      magnocellular dysfunction in schizophrenia therefore permits evaluation of
      underlying etiologic hypotheses. OBJECTIVES: To evaluate magnocellular
      dysfunction in schizophrenia, relative to known neurochemical and neuroanatomical
      substrates, and to examine relationships between electrophysiological and
      behavioral measures of visual pathway dysfunction and relationships with higher
      cognitive deficits. DESIGN, SETTING, AND PARTICIPANTS: Between-group study at an
      inpatient state psychiatric hospital and outpatient county psychiatric
      facilities. Thirty-three patients met DSM-IV criteria for schizophrenia or
      schizoaffective disorder, and 21 nonpsychiatric volunteers of similar ages
      composed the control group. MAIN OUTCOME MEASURES: (1) Magnocellular and
      parvocellular evoked potentials, analyzed using nonlinear (Michaelis-Menten) and
      linear contrast gain approaches; (2) behavioral contrast sensitivity measures;
      (3) white matter integrity; (4) visual and nonvisual neuropsychological measures,
      and (5) clinical symptom and community functioning measures. RESULTS: Patients
      generated evoked potentials that were significantly reduced in response to
      magnocellular-biased, but not parvocellular-biased, stimuli (P = .001). Michaelis
      Menten analyses demonstrated reduced contrast gain of the magnocellular system (P
      = .001). Patients showed decreased contrast sensitivity to magnocellular-biased
      stimuli (P<.001). Evoked potential deficits were significantly related to
      decreased white matter integrity in the optic radiations (P<.03). Evoked
      potential deficits predicted impaired contrast sensitivity (P = .002), which was
      in turn related to deficits in complex visual processing (P< or =.04). Both
      evoked potential (P< or =.04) and contrast sensitivity (P = .01) measures
      significantly predicted community functioning. CONCLUSIONS: These findings
      confirm the existence of early-stage visual processing dysfunction in
      schizophrenia and provide the first evidence that such deficits are due to
      decreased nonlinear signal amplification, consistent with glutamatergic theories.
      Neuroimaging studies support the hypothesis of dysfunction within low-level
      visual pathways involving thalamocortical radiations. Deficits in early-stage
      visual processing significantly predict higher cognitive deficits.

PMID- 15867103
TI  - Results of a multisite randomized trial of supported employment interventions for
      individuals with severe mental illness.
AB  - CONTEXT: National probability surveys indicate that most individuals with
      schizophrenia and other severe mental illnesses are not employed. This multisite
      study tested the effectiveness of supported employment (SE) models combining
      clinical and vocational rehabilitation services to establish competitive
      employment. METHODS: We randomly assigned 1273 outpatients with severe mental
      illness from 7 states in the United States to an experimental SE program or to a
      comparison or a services-as-usual condition, with follow-up for 24 months.
      Participants were interviewed semiannually, paid employment was tracked weekly,
      and vocational and clinical services were measured monthly. Mixed-effects random
      regression analysis was used to predict the likelihood of competitive employment,
      working 40 or more hours in a given month, and monthly earnings. RESULTS:
      Cumulative results during 24 months show that experimental group participants
      (359/648 [55%]) were more likely than those in the comparison programs (210/625
      [34%]) to achieve competitive employment (chi(2) = 61.17; P<.001). Similarly,
      patients in experimental group programs (330/648 [51%]) were more likely than
      those in comparison programs (245/625 [39%]) to work 40 or more hours in a given
      month (chi(2) = 17.66; P<.001). Finally, participants in experimental group
      programs had significantly higher monthly earnings than those in the comparison
      programs (mean, US 122 dollars/mo [n=639] vs US 99 dollars/mo [n=622]); t(1259) =
      -2.04; P<.05). In the multivariate longitudinal analysis, experimental condition
      subjects were more likely than comparison group subjects to be competitively
      employed, work 40 or more hours in a given month, and have higher earnings,
      despite controlling for demographic, clinical, work history, disability
      beneficiary status, and study site confounders. Moreover, the advantage of
      experimental over comparison group participants increased during the 24-month
      study period. CONCLUSION: The SE models tailored by integrating clinical and
      vocational services were more effective than services as usual or unenhanced
      services.

PMID- 15867104
TI  - Chronic depression: medication (nefazodone) or psychotherapy (CBASP) is effective
      when the other is not.
AB  - CONTEXT: Although various strategies are available to manage nonresponders to an
      initial treatment for depression, no controlled trials address the utility of
      switching from an antidepressant medication to psychotherapy or vice versa.
      OBJECTIVE: To compare the responses of chronically depressed nonresponders to 12
      weeks of treatment with either nefazodone or cognitive behavioral analysis system
      of psychotherapy (CBASP) who were crossed over to the alternate treatment
      (nefazodone, n = 79; CBASP, n = 61). DESIGN: Crossover trial. SETTING: Twelve
      academic outpatient psychiatric centers. PATIENTS: There were 140 outpatients
      with chronic major depressive disorder; 92 (65.7%) were female, 126 (90.0%) were
      white, and the mean age was 43.1 years. Thirty participants dropped out of the
      study prematurely, 22 in the nefazodone group and 8 in the CBASP group.
      INTERVENTIONS: Treatment lasted 12 weeks. The dosage of nefazodone was 100 to 600
      mg/d; CBASP was provided twice weekly during weeks 1 through 4 and weekly
      thereafter. MAIN OUTCOME MEASURES: The 24-item Hamilton Rating Scale for
      Depression, administered by raters blinded to treatment, the Clinician Global
      Impressions-Severity scale, and the 30-item Inventory for Depressive
      Symptomatology-Self-Report. RESULTS: Analysis of the intent-to-treat sample
      revealed that both the switch from nefazodone to CBASP and the switch from from
      CBASP to nefazodone resulted in clinically and statistically significant
      improvements in symptoms. Neither the rates of response nor the rates of
      remission were significantly different when the groups of completers were
      compared. However, the switch to CBASP following nefazodone therapy was
      associated with significantly less attrition due to adverse events, which may
      explain the higher intent-to-treat response rate among those crossed over to
      CBASP (57% vs 42%). CONCLUSIONS: Among chronically depressed individuals, CBASP
      appears to be efficacious for nonresponders to nefazodone, and nefazodone appears
      to be effective for CBASP nonresponders. A switch from an antidepressant
      medication to psychotherapy or vice versa appears to be useful for nonresponders
      to the initial treatment.

PMID- 15867105
TI  - Predicting depression following mild traumatic brain injury.
AB  - CONTEXT: Minimizing negative consequences of major depression following traumatic
      brain injury is an important public health objective. Identifying high-risk
      patients and referring them for treatment could reduce morbidity and loss of
      productivity. OBJECTIVE: To develop a model for early screening of patients at
      risk for major depressive episode at 3 months after traumatic brain injury.
      DESIGN: Prediction model using receiver operating characteristic curve. SETTING:
      Level I trauma center in a major metropolitan area. PARTICIPANTS: Prospective
      cohort of 129 adults with mild traumatic brain injury. MAIN OUTCOME MEASURES:
      Center for Epidemiologic Studies Depression Scale score and current major
      depressive episode module of the Structured Clinical Interview for the DSM-IV.
      RESULTS: A prediction model including higher 1-week Center for Epidemiologic
      Studies Depression Scale score, older age, and computed tomographic scans of
      intracranial lesions yielded 93% sensitivity and 62% specificity. CONCLUSION:
      This study supports the feasibility of identifying patients with mild traumatic
      brain injury who are at high risk for developing major depressive episode by 3
      months' postinjury, which could facilitate selective referral for potential
      treatment and reduction of negative outcomes.

PMID- 15867106
TI  - The interaction of stressful life events and a serotonin transporter polymorphism
      in the prediction of episodes of major depression: a replication.
AB  - CONTEXT: Prior evidence from twin studies suggested genetic moderation of the
      depressogenic effects of stressful life events (SLEs). Can the specific genes
      involved in this effect be identified? OBJECTIVE: To replicate and extend a
      recent study that a functional variant in the serotonin transporter (5-HTT) might
      in part explain these findings. DESIGN: Characterizing risk for major depression
      and generalized anxiety syndrome in the last year as a function of 5-HTT
      genotype, sex, and the occurrence of SLEs and ratings of the SLE-associated level
      of threat. SETTING: A population-based sample of adult twins. PARTICIPANTS: Five
      hundred forty-nine male and female twins with a mean age at participation of 34.9
      years (SD 9.1). MAIN OUTCOME MEASURE: Episodes of major depression and
      generalized anxiety syndrome in the last year with onset measured to the nearest
      month. RESULTS: Individuals with 2 short (S) alleles at the 5-HTT locus were more
      sensitive to the depressogenic effects of all SLEs than were those with 1 or 2
      long (L) alleles. When level of SLE-associated threat was examined, the
      interaction between genotype and SLE resulted from an increased sensitivity of SS
      individuals to the depressogenic effects of common low-threat events. These
      events had little impact on risk for those possessing the SL and LL genotypes.
      The 5-HTT genotype did not modify the effects of SLEs on risk for generalized
      anxiety syndrome. CONCLUSION: Variation at the 5-HTT moderates the sensitivity of
      individuals to the depressogenic effects of SLEs largely by producing, in SS
      individuals, an increased sensitivity to the impact of mild stressors.
      Replication of these intriguing results is needed.

PMID- 15867107
TI  - Influence of serotonin transporter promoter region polymorphisms on hippocampal
      volumes in late-life depression.
AB  - CONTEXT: Polymorphisms in the promoter region of the serotonin transporter gene
      (5-HTTLPR) influence transcription and may play a role in the pathogenesis and
      course of depression. Recent research demonstrates that specific polymorphisms
      may be associated with differences in hippocampal volumes in subjects with
      depression. OBJECTIVE: To examine associations between 5-HTTLPR genotype and
      hippocampal volumes in elderly control subjects and elderly subjects classified
      as having early or late onset of depression. DESIGN: Cohort study examining
      baseline characteristics. PARTICIPANTS: Subjects were community dwelling and 60
      years or older. Using a definition of early-onset depression as depression first
      occurring at 50 years or younger, we examined 72 subjects with early-onset
      depression, 63 subjects with late-onset depression, and 83 healthy control
      subjects. MAIN OUTCOME MEASURES: All subjects underwent genotyping for the 5
      HTTLPR and underwent brain magnetic resonance imaging. Analyses of hippocampal
      volumes were controlled for total cerebral volume, age, and sex. RESULTS: The
      interaction between diagnosis and 5-HTTLPR genotype was statistically significant
      for the right hippocampus (P = .04). Subjects with late-onset depression who were
      homozygous for the long (L) allele (L /L genotype) had significantly smaller
      right hippocampal volumes than did L /L subjects with early-onset depression (P =
      .046) or L /L control subjects (P = .01). Post hoc analyses showed that later age
      of depression onset was associated with smaller hippocampal volumes in subjects
      with the L /L genotype, but earlier age of onset was associated with smaller
      hippocampal volumes in subjects who were homozygous for the short (S) allele (S/S
      genotype). CONCLUSIONS: Subjects with late-onset depression who were homozygous
      for the L allele exhibited smaller hippocampal volumes than other groups.
      Genotype also mediated the effect of age of onset on hippocampal volumes. Our
      findings differ from previous work; however, we examined an older and larger
      cohort of subjects than previous studies. Possible explanations for these
      findings include interactions between the serotonergic system and neurotrophic
      factors or cortisol response to stresses, each of which may affect hippocampal
      volumes.

PMID- 15867108
TI  - Psychopathology among New York city public school children 6 months after
      September 11.
AB  - CONTEXT: Children exposed to a traumatic event may be at higher risk for
      developing mental disorders. The prevalence of child psychopathology, however,
      has not been assessed in a population-based sample exposed to different levels of
      mass trauma or across a range of disorders. OBJECTIVE: To determine prevalence
      and correlates of probable mental disorders among New York City, NY, public
      school students 6 months following the September 11, 2001, World Trade Center
      attack. DESIGN: Survey. SETTING: New York City public schools. PARTICIPANTS: A
      citywide, random, representative sample of 8236 students in grades 4 through 12,
      including oversampling in closest proximity to the World Trade Center site
      (ground zero) and other high-risk areas. MAIN OUTCOME MEASURE: Children were
      screened for probable mental disorders with the Diagnostic Interview Schedule for
      Children Predictive Scales. RESULTS: One or more of 6 probable anxiety/depressive
      disorders were identified in 28.6% of all children. The most prevalent were
      probable agoraphobia (14.8%), probable separation anxiety (12.3%), and probable
      posttraumatic stress disorder (10.6%). Higher levels of exposure correspond to
      higher prevalence for all probable anxiety/depressive disorders. Girls and
      children in grades 4 and 5 were the most affected. In logistic regression
      analyses, child's exposure (adjusted odds ratio, 1.62), exposure of a child's
      family member (adjusted odds ratio, 1.80), and the child's prior trauma (adjusted
      odds ratio, 2.01) were related to increased likelihood of probable
      anxiety/depressive disorders. Results were adjusted for different types of
      exposure, sociodemographic characteristics, and child mental health service use.
      CONCLUSIONS: A high proportion of New York City public school children had a
      probable mental disorder 6 months after September 11, 2001. The data suggest that
      there is a relationship between level of exposure to trauma and likelihood of
      child anxiety/depressive disorders in the community. The results support the need
      to apply wide-area epidemiological approaches to mental health assessment after
      any large-scale disaster.

PMID- 15867109
TI  - Neighborhood residence and mental health problems of 5- to 11-year-olds.
AB  - CONTEXT: Little research has investigated possible effects of neighborhood
      residence on mental health problems in children such as depression, anxiety, and
      withdrawal. OBJECTIVE: To examine whether children's mental health is associated
      with neighborhood structural characteristics (concentrated disadvantage,
      immigrant concentration, and residential stability) and whether neighborhood
      social processes (collective efficacy and organizational participation) underlie
      such effects. DESIGN AND SETTING: The Project on Human Development in Chicago
      Neighborhoods is a multilevel, longitudinal study of a representative sample of
      children aged 5 to 11 years in the late 1990s recruited from 80 neighborhoods. A
      community survey assessing neighborhood social processes was conducted with an
      independent sample of adult residents in these 80 neighborhoods and is used in
      conjunction with US census data to assess neighborhood conditions. PARTICIPANTS:
      A total of 2805 children (18.1% European American, 33.8% African American, and
      48.1% Latino) and their primary caregivers were seen twice. MAIN OUTCOME
      MEASURES: Child Behavior Checklist total raw and clinical cutoff scores for
      internalizing behavior problems (depression, anxiety, withdrawal, and somatic
      problems). RESULTS: The percentages of children above the clinical threshold were
      21.5%, 18.3%, and 11.5% in neighborhoods of low, medium, and high socioeconomic
      status, respectively. A substantial proportion of variance in children's total
      internalizing scores (intraclass correlation, 11.1%) was attributable to between
      neighborhood differences. Concentrated disadvantage was associated with more
      mental health problems and a higher number of children in the clinical range,
      after accounting for family demographic characteristics, maternal depression, and
      earlier child mental health scores. Neighborhood collective efficacy and
      organizational participation were associated with better mental health, after
      accounting for neighborhood concentrated disadvantage. Collective efficacy
      mediated the effect of concentrated disadvantage. CONCLUSIONS: A large number of
      children in poor neighborhoods have mental health problems. The mechanism through
      which neighborhood economic effects operated was community social control and
      cohesion, which may be amenable to intervention.

PMID- 15867110
TI  - Variability of familial risk of Alzheimer disease across the late life span.
AB  - CONTEXT: The role of genetic factors in Alzheimer disease (AD) varies across the
      late life span, complicating efforts to quantify the risk of AD for relatives of
      probands with AD. OBJECTIVES: To visualize the changing levels of familial risk
      according to proband onset age and the age of the at-risk relative and to
      determine the familiality of age at onset in AD. DESIGN: A retrospective,
      informant-based family study. SETTING, PATIENTS, AND OTHER PARTICIPANTS: Siblings
      and parents of probands with AD (relatives = 4687; probands = 904), ascertained
      at geriatric clinic and nursing home settings, and of elderly probands without
      dementia (relatives = 7649; probands = 1525) who were spouses of probands,
      participants at senior centers, or nursing home residents without dementia. MAIN
      OUTCOME MEASURES: Informant-based assessments of AD in the relatives were used to
      generate 3-dimensional surfaces representing the patterns of risk of AD across
      the late life span depending on the specific onset age of the proband with AD (or
      assessment age of the elderly proband without dementia). We then constructed a 3
      dimensional, age-specific, 10-year hazard rate ratio (HRR) surface representing
      the relative risk of AD in relatives of probands with AD with smoothly shifting
      levels of onset age compared with relatives of elderly probands without dementia.
      RESULTS: The HRR surface peaked (HRR, 13.0) for younger sexagenarian relatives
      related to probands with AD with onset age in their early 60s. The HRRs dropped
      sharply both as the proband age at onset and the age of the relative increased.
      For relatives aged in their late 80s, the HRR fell lower than 2.0 regardless of
      proband onset age and their lower-limit 95% confidence intervals were less than
      1.0. CONCLUSIONS: The role of genetic risk factors decreases with increasing
      onset age of the proband with AD regardless of the age of the relatives
      themselves. The familiality of onset age is greatly reduced at later ages. The
      role of environmental risk factors in AD likely increases with onset age.

PMID- 15867113
TI  - What is new related to Helicobacter pylori infection in children and teenagers?
AB  - Helicobacter pylori infection is a common bacterial infection for humans, and the
      organism is the most prevalent gastric microbial pathogen. However, the major
      route of transmission remains poorly understood. The outcome of chronic H pylori
      infection varies from asymptomatic gastritis to peptic ulceration and gastric
      malignancies. Recently, H pylori has been associated with the development of
      extradigestive disorders, including refractory iron-deficiency (sideropenic)
      anemia and chronic autoimmune thrombocytopenic purpura. Virulence factors of H
      pylori and host genetic factors are both considered important determinants of
      disease outcome. Multiple tests, including novel noninvasive approaches, are
      available for establishing the presence of H pylori infection, but there is still
      little consensus about which study should be performed and in what clinical
      setting. Eradicating H pylori uses combination therapy, including a proton pump
      inhibitor and 2 antibiotics taken twice daily for 7 to 14 days. Antibiotic
      resistance is a growing and serious problem that interferes with the success of
      eradication therapy. Testing and eradication therapy for H pylori are currently
      recommended only for the subset of infected persons in whom the disease sequelae
      are proven or highly suspected.

PMID- 15867114
TI  - A randomized trial of primary care provider prompting to enhance preventive
      asthma therapy.
AB  - BACKGROUND: Guidelines recommend preventive medications for all children with
      persistent asthma, yet young urban children often receive inadequate therapy.
      This may occur in part because primary care providers are unaware of the severity
      of their patients' symptoms. OBJECTIVE: To determine whether systematic school
      based asthma screening, coupled with primary care provider notification of asthma
      severity, will prompt providers to take preventive medication action (prescribe a
      new preventive medication or change a current dose). DESIGN: Children aged 3 to 7
      years with mild persistent to severe persistent asthma were identified at the
      start of the 2002-2003 school year in Rochester. Children were assigned randomly
      to a provider notification group (child's primary care provider notified of
      asthma severity) or a control group (provider not notified of severity). Primary
      care providers of children in the provider notification group were sent a
      facsimile indicating the child's symptoms and recommending medication action
      based on national criteria. Interviewers blinded to the child's group assignment
      called parents 3 to 6 months later to determine if preventive actions were taken.
      RESULTS: Of 164 eligible children with mild persistent or more severe asthma, 151
      (92.1%) were enrolled. Children in the provider notification group were not more
      likely to receive a preventive medication action than were children in the
      control group (21.9% vs 26.0%; P = .57). Additional preventive measures,
      including encouraging compliance with medications (33.3% vs 31.3%; P = .85),
      recommending environmental modifications (39.3% vs 42.4%; P = .86), and referrals
      for specialty care (6.6% vs 6.0%; P > .99), also did not differ between the
      provider notification and control groups. At the end of the study, 52.4% of
      children in both groups with no medication changes were still experiencing
      persistent symptoms. CONCLUSIONS: School-based asthma screening identified many
      symptomatic children in need of medication modification. Provider notification,
      however, did not improve preventive care. Findings suggest that more powerful
      interventions are needed to make systematic asthma screening effective.

PMID- 15867115
TI  - A multisite randomized trial of the effects of physician education and
      organizational change in chronic asthma care: cost-effectiveness analysis of the
      Pediatric Asthma Care Patient Outcomes Research Team II (PAC-PORT II).
AB  - BACKGROUND: A decision to implement innovative disease management interventions
      in health plans often requires evidence of clinical benefit and financial impact.
      The Pediatric Asthma Care Patient Outcomes Research Team II trial evaluated 2
      asthma care strategies: a peer leader-based physician behavior change
      intervention (PLE) and a practice-based redesign called the planned asthma care
      intervention (PACI). OBJECTIVE: To estimate the cost-effectiveness of the
      interventions. METHODS: This was a 3-arm, cluster randomized trial conducted in
      42 primary care practices. A total of 638 children (age range, 3-17 years) with
      mild to moderate persistent asthma were followed up for 2 years. Practices were
      randomized to PLE (n = 226), PACI (n = 213), or usual care (n = 199). The primary
      outcome was symptom-free days (SFDs). Costs included asthma-related health care
      utilization and intervention costs. RESULTS: Annual costs per patient were as
      follows: PACI, USD 1292; PLE, USD 504; and usual care, USD 385. The difference in
      annual SFDs was 6.5 days (95% confidence interval [CI], -3.6 to 16.9 days) for
      PLE vs usual care and 13.3 days (95% CI, 2.1-24.7 days) for PACI vs usual care.
      Compared with usual care, the incremental cost-effectiveness ratio was USD 18 per
      SFD gained for PLE (95% CI, USD 5.21-dominated) and USD 68 per SFD gained for
      PACI (95% CI, USD 37.36-361.16). CONCLUSIONS: Results of this study show that it
      is possible to increase SFDs in children and move organizations toward guideline
      recommendations on asthma control in settings where most children are receiving
      controller medications at baseline. However, the improvements were realized with
      an increase in the costs associated with asthma care.

PMID- 15867116
TI  - Comparison of monocular autorefraction to comprehensive eye examinations in
      preschool-aged and younger children.
AB  - BACKGROUND: Monocular autorefraction is a newly available technology for vision
      screening that has been advocated to test young children. Such devices
      automatically determine the refractive state of each eye, but cannot directly
      detect amblyopia or strabismus. OBJECTIVE: To compare the results of a
      commercially available monocular autorefractor (SureSight; Welch Allyn Medical
      Products, Skaneateles Falls, NY) with findings from a comprehensive eye
      examination for significant refractive error, strabismus, and amblyopia. METHODS:
      Children 5 years and younger who were new patients attending a pediatric
      ophthalmology clinic were tested with the monocular autorefractor without
      dilation and underwent a comprehensive eye examination that included dilation.
      MAIN OUTCOME MEASURES: The proportion of children who could be tested and the
      sensitivity and specificity of the screening. RESULTS: Of the 170 children
      enrolled (age, <3 years, n = 80; age range, 3-5 years, n = 90), 36% had abnormal
      eye examination findings. Most (84%) children 3 years or older could be tested
      compared with 49% of the children younger than 3 years (P<.001). Among those who
      were testable, for children younger than 3 years the sensitivity was 80% (95%
      confidence interval [CI], 44%-97%) and the specificity was 41% (95% CI, 24%-61%).
      For children aged 3 to 5 years, the sensitivity was 88% (95% CI, 68%-97%) and the
      specificity was 58% (95% CI, 43%-71%). CONCLUSIONS: Our findings suggest that
      screening children aged 3 to 5 years with monocular autorefraction would identify
      most cases of visual impairment but would be associated with many false-positive
      results. For children younger than 3 years, testability was low and results were
      nonspecific.

PMID- 15867118
TI  - HIV/STD risk reduction interventions for African American and Latino adolescent
      girls at an adolescent medicine clinic: a randomized controlled trial.
AB  - BACKGROUND: Adolescent girls in the United States and around the world are at a
      heightened risk for sexually transmitted diseases (STDs), including human
      immunodeficiency virus (HIV). OBJECTIVE: To determine the efficacy of a skill
      based HIV/STD risk-reduction intervention in reducing self-reported unprotected
      sexual intercourse among African American and Latino adolescent girls. DESIGN:
      Randomized controlled trial with 3-, 6-, and 12-month follow-ups. SETTING AND
      PARTICIPANTS: Sexually experienced African American and Latino adolescent girls
      recruited from the adolescent medicine clinic of a children's hospital serving a
      low-income inner-city community (N = 682, mean age, 15.5 years); 88.6% were
      retained at the 12-month follow-up. INTERVENTIONS: Three 250-minute interventions
      based on cognitive-behavioral theories and elicitation research: an information
      based HIV/STD intervention provided information necessary to practice safer sex;
      a skill-based HIV/STD intervention provided information and taught skills
      necessary to practice safer sex; or a health-promotion control intervention
      concerned with health issues unrelated to sexual behavior. MAIN OUTCOME MEASURES:
      Primary outcome measure was self-reported frequency of unprotected sexual
      intercourse; secondary outcomes included the frequency of sexual intercourse
      while intoxicated, the number of sexual partners, biologically confirmed STDs,
      and theoretical mediator variables, including the intention to use condoms,
      beliefs about using condoms, and condom-use knowledge. RESULTS: No differences
      between the information intervention and the health control intervention were
      statistically significant. Skills-intervention participants (mean [SE], 2.27
      [0.81]) reported less unprotected sexual intercourse at the 12-month follow-up
      than did information-intervention participants (mean [SE], 4.04 [0.80]; P = .03),
      or health control-intervention participants (mean [SE], 5.05 [0.81]; P = .002).
      At the 12-month follow-up, skills-intervention participants (mean [SE], 0.91
      [0.05]) reported fewer sexual partners (P = .04) compared with health control
      intervention participants (mean [SE], 1.04 [0.05]) and were less likely to test
      positive for STD (mean [SE], 10.5% [2.9%]) than were health control-intervention
      participants (mean [SE], 18.2% [2.8%]; P = .05). No differences in the frequency
      of unprotected sexual intercourse, the number of partners, or the rate of STD
      were observed at the 3- or 6-month follow-up between skill-intervention
      participants and information-intervention or health control-intervention
      participants. CONCLUSION: Skill-based HIV/STD interventions can reduce sexual
      risk behaviors and STD rate among African American and Latino adolescent girls in
      clinic settings.

PMID- 15867119
TI  - Screening for children's exposure to environmental tobacco smoke in a pediatric
      primary care setting.
AB  - BACKGROUND: The American Academy of Pediatrics (Elk Grove Village, Ill) has
      recommended that pediatricians assess their patients' environmental tobacco smoke
      (ETS) exposure, but the specific questions most likely to identify children with
      high ETS exposure are not known. Cotinine is a nicotine metabolite, present in
      hair, that can be used to quantify months of ETS exposure. OBJECTIVE: To develop
      a brief screening tool that will accurately predict ETS exposure as defined by
      child hair cotinine level. METHODS: We compared the performance of a series of
      easily administered screening questions regarding home ETS exposure to child hair
      cotinine levels. Subjects were a convenience sample of healthy children aged 2
      weeks to 3 years of both self-reported smokers and nonsmokers. RESULTS: Hair
      samples and questionnaire data were obtained from 291 children. Based on clinical
      applicability and statistical significance, 3 questions ("Does the mother
      smoke?", "Do others smoke?", and "Do others smoke inside?") were selected as a
      valid screening tool to determine children's ETS exposure risk. Maternal report
      of smoking outside only or smoking few cigarettes per day had no impact on child
      hair cotinine levels. CONCLUSIONS: It was possible to derive a simple, specific,
      and valid screening tool that can be used in pediatric offices to identify
      children at risk for ETS exposure. Further research is needed to test this tool
      prospectively.

PMID- 15867120
TI  - A randomized trial of practice-based education to improve delivery systems for
      anticipatory guidance.
AB  - BACKGROUND: Communication between physicians and patients is an important
      component of medical encounters and has been identified by the Institute of
      Medicine as a point of intervention to increase quality of care. In pediatric
      health maintenance visits, substantial recommended communication, in the form of
      anticipatory guidance, is not provided. OBJECTIVE: To examine the effectiveness
      of an intervention of continuing medical education and process improvement
      methods to implement "office systems" to improve the delivery of anticipatory
      guidance for parents of young children. METHODS: We performed a randomized
      controlled trial of a practice-based quality improvement intervention among 44
      pediatric practices in North Carolina. In the 22 intervention practices, project
      staff coached practice staff in auditing performance and identifying, testing,
      and implementing new care processes to improve delivery of anticipatory guidance.
      We surveyed parents of 1-month-olds and 6-month-olds regarding their recollection
      of anticipatory guidance as well as parent knowledge and parent behaviors and
      used cluster analysis to determine the effects of the intervention. RESULTS: The
      proportion of parents of 1-month-olds who reported that they received all age
      appropriate anticipatory guidance changed from 15.9% (95% confidence interval
      [CI], 8.9%-26.7%) to 10.0% (95% CI, 5.1%-18.8%) in the control practices and from
      7.3% (4.1%-12.9%) to 24.0% (95% CI, 14.6%-36.9%) in the intervention practices
      (difference between 2 differences, P = .002). The proportion of parents of 6
      month-olds who reported that they received all age-appropriate anticipatory
      guidance changed from 8.2% (95% CI, 3.6%-17.8%) to 5.4% (95% CI, 2.8%-10.2%) in
      the control practices and from 2.2% (95% CI, 0.8%-5.9%) to 18.1% (95% CI, 10.3%
      29.9%) in the intervention practices (difference between 2 differences, P =
      .001). There were no differences in self-reported parent knowledge and parent
      behavior. CONCLUSION: An office system intervention improved parent reports of
      quantity of anticipatory guidance but did not change parent knowledge or parent
      behavior. Future research should examine how to use systems improvement methods
      to improve the impact of anticipatory guidance.

PMID- 15867121
TI  - Impact of a quality improvement program on care and outcomes for children with
      asthma.
AB  - OBJECTIVE: To test a quality improvement intervention, a learning collaborative
      based on the Institute for Healthcare Improvement's Breakthrough Series
      methodology, specifically intended to improve care and outcomes for patients with
      childhood asthma. DESIGN: Randomized trial in primary care practices. SETTING:
      Practices in greater Boston, Mass, and greater Detroit, Mich. PARTICIPANTS: Forty
      three practices, with 13 878 pediatric patients with asthma, randomized to
      intervention and control groups. Intervention Participation in a learning
      collaborative project based on the Breakthrough Series methodology of continuous
      quality improvement. MAIN OUTCOME MEASURES: Change from baseline in the
      proportion of children with persistent asthma who received appropriate medication
      therapy for asthma, and in the proportion of children whose parent received a
      written management plan for their child's asthma, as determined by telephone
      interviews with parents of 631 children. RESULTS: After adjusting for state,
      practice size, child age, sex, and within-practice clustering, no overall effect
      of the intervention was found. CONCLUSIONS: This methodologically rigorous
      assessment of a widely used quality improvement technique did not demonstrate a
      significant effect on processes or outcomes of care for children with asthma.
      Potential deficiencies in program implementation, project duration, sample
      selection, and data sources preclude making the general inference that this type
      of improvement program is ineffective. Additional rigorous studies should be
      undertaken under more optimal settings to assess the efficacy of this method for
      improving care.

PMID- 15867122
TI  - Factors associated with refusal of childhood vaccines among parents of school
      aged children: a case-control study.
AB  - BACKGROUND: The rate of nonmedical exemptions to school immunization requirements
      has been increasing, and children with exemptions have contributed to outbreaks
      of vaccine-preventable diseases. OBJECTIVES: To determine why parents claim
      nonmedical exemptions and to explore differences in perceptions of vaccines and
      vaccine information sources between parents of exempt and fully vaccinated
      children. DESIGN: Case-control study. SETTING: Colorado, Massachusetts, Missouri,
      and Washington. PARTICIPANTS: Surveys were mailed to the parents of 815 exempt
      children (cases) and 1630 fully vaccinated children (controls randomly selected
      from the same grade and school) recruited from 112 private and public elementary
      schools. Surveys were completed by 2435 parents (56.1%). MAIN OUTCOME MEASURES:
      Parental reports. RESULTS: Most children (209 [75.5%] of 277) with nonmedical
      exemptions received at least some vaccines. The most common vaccine not received
      was varicella (147 [53.1%] of 277 exempt children). The most common reason stated
      for requesting exemptions (190 [69%] of 277) was concern that the vaccines might
      cause harm. Parents of exempt children were significantly more likely than
      parents of vaccinated children to report low perceived vaccine safety and
      efficacy, a low level of trust in the government, and low perceived
      susceptibility to and severity of vaccine-preventable diseases. Parents of exempt
      children were significantly less likely to report confidence in medical, public
      health, and government sources for vaccine information and were more likely to
      report confidence in alternative medicine professionals than parents of
      vaccinated children. CONCLUSION: Continued efforts must be made to educate
      parents about the utility and safety of vaccines, especially parents requesting
      nonmedical exemptions to school immunization requirements.

PMID- 15867123
TI  - Effect of activity restriction owing to heart disease on obesity.
AB  - OBJECTIVE: To determine whether exercise intolerance and recommended activity
      restrictions are associated with development of overweight and obesity in
      children with congenital heart disease. DESIGN: Retrospective review. SETTING:
      Pediatric cardiology practice at a teaching hospital. PARTICIPANTS: A total of
      110 pediatric congenital heart disease patients followed up for a mean of 8.4
      years. MAIN OUTCOME MEASURES: Body mass index (BMI), sex-appropriate BMI
      percentiles, overweight (BMI percentile > or =85), and obesity (BMI percentile >
      or =95) at follow-up. RESULTS: As a group, the increase in BMI percentiles was
      close to 10 points, but the increase was 21.6 points for exercise intolerant
      children and 27.3 points for activity restricted children. Activity restriction
      was significantly associated with both overweight (risk ratio [RR], 2.60; 95%
      confidence interval [CI], 1.34-3.54) and obesity at follow-up (RR, 4.08; 95% CI,
      1.42-7.38) after adjusting for weight at baseline. For the subset of 92 children
      at a healthy weight at baseline, activity restriction was again significantly
      associated with overweight (RR, 2.51; 95% CI, 1.24-3.52) and obesity (RR, 6.14;
      95% CI, 2.54-8.82) at follow-up. Exercise intolerance did not attain statistical
      significance. CONCLUSIONS: Exercise intolerant and activity restricted children
      experienced larger increases in absolute BMI and BMI percentile than children
      with neither exercise intolerance nor activity restriction. Activity restriction
      was the strongest predictor of risk of overweight and obesity at follow-up.
      Elevated weight and obesity may cause these children significant additional
      health burdens. Therefore, when patients must be counseled against physical
      exertion, they also need to be educated about the importance of appropriate
      physical activity and good dietary practices.

PMID- 15867124
TI  - Taking well-child care into the 21st century: a novel, effective method for
      improving parent knowledge using computerized tutorials.
AB  - BACKGROUND: Despite expert panel recommendations, few pediatric providers
      administer sufficient anticipatory guidance and educational counseling during
      well-child visits, largely owing to lack of time. OBJECTIVES: To design a waiting
      room educational kiosk that uses interactive, self-guided, computerized tutorials
      to give anticipatory guidance to parents at the 6-week and 4-month well-child
      visits, and assess impact on parent knowledge. The intervention required no
      additional provider time, and automatically printed a summary for the medical
      record. SETTING: A government-funded hospital serving Navajo patients in New
      Mexico. METHODS: After a well-child visit, knowledge regarding issues such as
      fever management, dental care, sleep position, nutrition, and car seat use was
      tested in a group of parents receiving standard care (control), and a group using
      the computerized tutorials in addition to standard care (intervention). RESULTS:
      Fifty-two parents in the control group and 49 parents in the intervention group
      completed the knowledge assessment. Ninety-five percent of intervention subjects
      completed the computerized tutorial without clinic staff involvement. Compared
      with the control group, the intervention group had superior knowledge in all
      tested areas. The percentage of correct responses to all questions was higher for
      the intervention group in the following categories: car seat use (49% vs 31%,
      P<.01), dental care (80% vs 27%, P<.001), and nutrition (43% vs 21%, P<.001).
      Among parents of 6-week-old infants, a greater number of parents in the
      intervention group identified fever as 100.4 degrees F or higher (86% vs 50%,
      P<.001), and fewer replied that they would give antipyretics to a febrile child
      younger than 3 months old without consulting a provider (52% vs 100%, P<.001).
      The percentage of parents with a perfect score or only one question wrong on the
      21-item test was 17-fold higher in the intervention group (P<.001). CONCLUSION:
      Computerized anticipatory guidance at well-child visits increases knowledge over
      printed materials alone and is usable by the majority of parents.

PMID- 15867125
TI  - Effect of using 2 throat swabs vs 1 throat swab on detection of group A
      streptococcus by a rapid antigen detection test.
AB  - OBJECTIVE: To assess the effect of using 2 throat swabs vs 1 on rapid detection
      of group A streptococcus by the STREP A OIA MAX (hereafter, OIA MAX) test.
      METHODS: Children aged 5 to 18 years with acute pharyngitis were randomized to 1
      of 2 study groups. In group 1, one throat swab was obtained, streaked first on
      sheep blood agar, and then used for OIA MAX testing. In group 2, two throat swabs
      were obtained simultaneously. One swab was streaked first on sheep blood agar and
      then joined with the other swab for OIA MAX testing. In both groups, the pledgets
      in the collection-transport tube were incubated in Todd-Hewitt broth. A positive
      group A streptococcus culture either by sheep blood agar or Todd-Hewitt broth was
      confirmed by a latex agglutination test. RESULTS: Three hundred sixty-three
      patients were enrolled, 177 in group 1 and 186 in group 2. Cultures were positive
      for group A streptococcus in 154 (42.4%) of 363 patients. The sensitivity and
      specificity of OIA MAX testing were 94.7% and 100.0%, respectively, in group 1,
      and 92.4% and 96.3%, respectively, in group 2. There was no statistical
      difference between the sensitivity, the specificity, and the predictive values of
      the OIA MAX test performed with 1 swab compared with those performed with 2 swabs
      (P>.10). There was no association between OIA MAX test sensitivity and the
      severity of pharyngitis as measured by the modified Centor criterion (history of
      fever, absence of cough, presence of pharyngeal or tonsillar exudates, and
      presence of cervical lymphadenopathy) scores. CONCLUSIONS: The OIA MAX test
      yielded comparable sensitivity and specificity in both study groups. The use of 2
      throat swabs instead of 1 swab did not increase the sensitivity of the OIA MAX
      test. The performance of the OIA MAX test did not depend on the severity of
      pharyngitis.

PMID- 15867126
TI  - Measuring the quality of care for group A streptococcal pharyngitis in 5 US
      health plans.
AB  - BACKGROUND: There is a high degree of professional consensus that children
      diagnosed with pharyngitis should only receive antibiotics if they have a
      positive test for group A streptococcus (GAS). OBJECTIVES: To develop and test
      the validity of a quality of care performance measure that examines GAS testing
      rates in children diagnosed with pharyngitis and prescribed an antibiotic.
      DESIGN: The measure developed examines the annual rate of GAS testing in children
      aged 2 to 18 years with an episode of pharyngitis who were prescribed
      antibiotics. The measure was tested for feasibility of implementation and
      validity in 5 health plans in the United States. Health plan administrative data
      were used to identify episodes of pharyngitis using International Classification
      of Diseases, Ninth Revision (ICD-9) codes 462, 463, and 034.0. Pharmacy data
      (National Drug Codes) were used to determine if antibiotics were prescribed for
      the pharyngitis episode. Laboratory claims data (Current Procedural Terminology
      codes) were used to determine whether a GAS test was performed. Rates of GAS
      testing in children with pharyngitis who received antibiotics were calculated for
      each health plan. Medical record abstractions were performed on a random sample
      (n = 465) of cases to assess percent agreement with laboratory claims data for
      GAS testing. Sensitivity of the administrative data for accurately identifying
      when GAS tests were performed was also assessed. RESULTS: Of the 120 158 children
      aged 2 to 18 years who had at least 1 episode of pharyngitis during the
      measurement year, 51 172 (43%) received antibiotics. Group A streptococcal
      testing rates for patients who were prescribed antibiotics varied widely among
      the participating health plans (59%-83% of cases; P<.05). Percent agreement
      between administrative and medical records data for GAS tests was 86%. The
      sensitivity of the administrative data for accurately identifying when GAS tests
      were performed was 85%. CONCLUSIONS: This quality measure is feasible to
      implement at the health plan level and validly assesses GAS testing rates using
      administrative data. The participating health plans are not performing GAS tests
      as indicated by current expert practice guidelines in a substantial proportion of
      cases. Improvements in adhering to these guidelines are warranted given the
      current levels of antibiotic overuse and antibiotic resistance nationally.

PMID- 15867127
TI  - Symptom-free day--$68; 2 weeks of childhood--priceless.

PMID- 15867128
TI  - How many pediatricians does it take to change a practice? or how to incorporate
      change into practice.

PMID- 15867129
TI  - Alcohol hand rub: a simple solution in search of champions.

PMID- 15867130
TI  - Baroreflex regulation of heart rate and sympathetic vasomotor tone in women and
      men.
AB  - Gender has been reported to influence baroreflex heart rate regulation and
      baroreflex blood pressure buffering. We tested the hypothesis that gender
      influences baroreflex regulation of heart rate and sympathetic vasomotor tone. We
      recruited 32 normal-weight healthy subjects (17 men and 15 women). ECGs for heart
      rate, brachial and finger blood pressure, and muscle sympathetic nerve activity
      (MSNA) were measured. Baroreflex heart rate and MSNA regulation were assessed
      using incremental phenylephrine and nitroprusside infusions. Baseline blood
      pressure was similar in men and women. MSNA was 21+/-2.5 bursts/min in women and
      19+/-2.8 bursts/min in men (NS). The gain of the baroreflex MSNA curves was
      similar in women and men (-1.9+/-0.2 bursts/min per mm Hg in men and -2.0+/-0.3
      bursts/min per mm Hg in women). Baroreflex gain for heart rate regulation was
      17+/-3.2 ms/mm Hg in women and 19+/-1.9 ms/mm Hg in men (NS). We conclude that
      baroreflex gains for heart rate and sympathetic MSNA regulation are similar in
      women and men. However, the probability for congruence between men and women in
      terms of the MSNA baroreflex curves was 0.06% for burst rate, 0.4% for burst
      incidence, and 0.01% for burst area. In women, the MSNA baroreflex curve may be
      shifted to slightly lower blood pressure such that at a given blood pressure MSNA
      tends to be lower.

PMID- 15867131
TI  - Sympatho-inhibitory action of endogenous adrenomedullin through inhibition of
      oxidative stress in the brain.
AB  - Central sympathetic activation is one of the possible mechanisms underlying
      hypertension, in which reactive oxygen species may play a role. Thus, we examined
      whether adrenomedullin, an antioxidant peptide, is involved in the central
      regulation of arterial pressure through sympatho-modulatory action.
      Adrenomedullin knockout mice were fed with high-salt diet for 4 weeks to
      stimulate adrenomedullin production. In the wild-type littermates, brain
      adrenomedullin content was significantly increased with salt loading, but not in
      the knockout mice. Intracerebroventricular hyperosmotic saline increased arterial
      pressure and sympathetic nerve activity in a dose-dependent fashion. With the
      normal salt diet, the hyperosmotic saline-induced response did not significantly
      differ between the knockout and wild-type mice; with the high-salt diet, however,
      the response was significantly greater in the knockout mice than in wild-type
      littermates (arterial pressure: 35.3+/-5.7% versus 20.1+/-2.1%, P<0.05;
      sympathetic nerve activity: 30.3+/-4.8% versus 15.9+/-1.5%, P<0.05;
      respectively). Moreover, pretreatment with 4-hydroxy-2,2,6,6
      tetramethylpiperidine-N-oxyl (tempol), a membrane-permeable superoxide dismutase
      mimetic, inhibited the augmented response to central hyperosmotic saline in salt
      loaded knockout mice. Consistently, the hyperosmotic saline-induced production of
      reactive oxygen species, measured by the lucigenin chemiluminescence method, was
      significantly greater in the isolated hypothalamus of salt-loaded knockout mice
      than in that of salt-loaded wild-type ones. In conclusion, endogenous
      adrenomedullin in the brain may inhibit sympathetic activation through its
      antioxidant action.

PMID- 15867132
TI  - Arterial elasticity as part of a comprehensive assessment of cardiovascular risk
      and drug treatment.
AB  - Early cardiovascular disease can be identified in asymptomatic individuals by
      noninvasive evaluation of functional and structural abnormalities of the
      vasculature and heart. These abnomalities are usually a consequence of
      endothelial dysfunction. A panel of 10 tests, including small and large artery
      elasticity, has been used as the basis for a screening system that provides a
      score of 0 to 20 as a guide to the severity of disease. Using that Rasmussen
      score allows for stratification of patients into low, intermediate, or high risk
      for progression to cardiovascular morbid events. This comprehensive screening can
      be performed efficiently in a single room with a single technician. The
      sensitivity and specificity of this screening system in predicting future
      cardiovascular events, its superiority to traditional risk factor assessment, and
      its potential to track the response to therapeutic interventions must be
      validated in long-term follow-up studies.

PMID- 15867133
TI  - Calcium-activated potassium channels and NO regulate human peripheral conduit
      artery mechanics.
AB  - The role of NO in the regulation of the mechanical properties of conduit arteries
      is controversial in humans, and the involvement of an endothelium-derived
      hyperpolarizing factor (EDHF), acting through calcium-activated potassium (KCa)
      channels, has never been investigated at this level in vivo. We assessed in
      healthy volunteers, after oral administration of aspirin (500 mg), the effect of
      local infusion of NG-monomethyl-L-arginine (L-NMMA; 8 mumol/min for 8 minutes),
      an NO synthase inhibitor, tetraethylammonium chloride (TEA; 9 mumol/min for 8
      minutes), a KCa channels inhibitor, and the combination of both on radial artery
      internal diameter, wall thickness (echo tracking), blood flow (Doppler), and
      pressure. The incremental elastic modulus and compliance were fitted as functions
      of midwall stress. L-NMMA decreased modulus and increased compliance at high
      levels of midwall stress (all P<0.05) without affecting radial diameter. TEA
      reduced radial diameter from 2.68+/-0.07 to 2.50+/-0.08 10(-3) m, increased the
      modulus, and decreased the compliance at all levels of stress (all P<0.05).
      Combination of both inhibitors synergistically enhanced the increase in modulus,
      the decrease in diameter (from 2.71+/-0.10 to 2.42+/-0.09 10(-3) m), and
      compliance compared with TEA alone (all P<0.05). These results confirm that
      inhibition of NO synthesis is associated with a paradoxical isometric smooth
      muscle relaxation of the radial artery. They demonstrate the involvement of KCa
      channels in the regulation of the mechanical properties of peripheral conduit
      arteries, supporting a role for EDHF at this level in vivo. Moreover, the
      synergistic effect of l-NMMA and TEA shows that KCa channels compensate for the
      loss of NO synthesis to maintain peripheral conduit artery diameter and
      mechanics.

PMID- 15867134
TI  - Orthostatic hypotension and supine hypertension in primary autonomic failure.

PMID- 15867135
TI  - Ascorbic acid selectively improves large elastic artery compliance in
      postmenopausal women.
AB  - The compliance of large elastic arteries in the cardiothoracic region decreases
      with advancing age/menopause and plays an important role in the increased
      prevalence of cardiovascular diseases in postmenopausal women. We determined
      whether oxidative stress contributes to the reduced large elastic artery
      compliance of postmenopausal women. Carotid artery compliance was measured during
      acute intravenous infusions of saline (baseline control) and supraphysiological
      doses of the potent antioxidant ascorbic acid in premenopausal (n=10; 23+/-1;
      mean+/-SE) and estrogen-deficient postmenopausal (n=21; 55+/-1 years) healthy
      sedentary women. Carotid artery compliance was 56% lower in postmenopausal
      compared with premenopausal women during baseline control (P<0.0001). Ascorbic
      acid infusion increased carotid artery compliance by 26% in postmenopausal women
      (1.11+/-0.07 to 1.38+/-0.08 mm2/mm Hgx10(-1); P<0.001) but had no effect in
      premenopausal women (2.50+/-0.25 versus 2.43+/-0.20 mm2/mm Hgx10(-1)). Carotid
      artery diameter, blood pressure, and heart rate were unaffected by ascorbic acid.
      In the pooled population, the change in arterial compliance with ascorbic acid
      correlated with baseline waist-to-hip ratio (r=0.56; P=0.001), plasma
      norepinephrine (r=0.58; P=0.001), and LDL cholesterol (r=0.54; P=0.001). These
      results suggest that oxidative stress may be an important mechanism contributing
      to the reduced large elastic artery compliance of sedentary, estrogen-deficient
      postmenopausal women. Increased abdominal fat storage, sympathetic nervous system
      activity, and LDL cholesterol may be mechanistically involved in oxidative stress
      associated suppression of arterial compliance in postmenopausal women.

PMID- 15867136
TI  - Proceedings of the 5th International Workshop on Structure and Function of Large
      Arteries, February 3-5, 2005, Paris, France.

PMID- 15867137
TI  - Out-of-office blood pressure measurement: a new era.

PMID- 15867138
TI  - Relationship of office, home, and ambulatory blood pressure to blood glucose and
      lipid variables in the PAMELA population.
AB  - Alterations in blood glucose and cholesterol are more frequently detectable in
      hypertensive than in normotensive conditions. However, no information exists as
      to whether this phenomenon involves only office or also home and 24-hour
      ambulatory blood pressure (ie, when values are representative of daily life). In
      2045 subjects enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni
      (PAMELA) study, we measured home, 24-hour, and office blood pressure.
      Measurements also included fasting blood glucose and serum total and HDL
      cholesterol values. Prevalence of diabetes (> or =126 mg/dL or use of
      antidiabetic drugs), impaired fasting blood glucose (> or =110 to <126 mg/dL),
      and hypercholesterolemia (serum total cholesterol > or =240 mg/dL or 200 mg/dL)
      increased progressively from "optimal" to "normal," "high-normal," and "elevated"
      office systolic or diastolic blood pressure. Fasting blood glucose and total
      serum cholesterol also increased progressively from the first to the fourth
      group, with HDL cholesterol values showing a concomitant progressive decrease.
      This was also the case for quartiles of office, home, and 24-hour blood pressure.
      In the whole population, there was a positive correlation between serum
      cholesterol or blood glucose and all blood pressure values (P always <0.0001),
      with a much smaller and less consistent relationship with heart rate. In a
      multivariate analysis that included gender, body mass index, age, and
      antihypertensive treatment, all blood pressure values remained highly
      significantly related to values of either metabolic variables. Thus, in the
      PAMELA population, glucose and lipid values are independently related to blood
      pressure. This is also the case when daily life blood pressure values are
      considered.

PMID- 15867139
TI  - Metabolic syndrome is associated with aortic stiffness in untreated essential
      hypertension.
AB  - Metabolic syndrome is a powerful predictor of cardiovascular disease in
      hypertension, and large-artery stiffness is increasingly recognized as a
      cardiovascular risk factor. We hypothesized that the adverse prognostic
      significance of the metabolic syndrome in hypertension might be explained in part
      by its association with aortic stiffness. A total of 169 newly diagnosed, never
      treated, nondiabetic patients with essential hypertension (men 55%, 48+/-11
      years) were classified by the presence (n=45) or absence (n=124) of the metabolic
      syndrome. All patients underwent aortic and upper limb pulse wave velocity
      determination by means of an applanation tonometry-based method. Aortic pulse
      wave velocity had a direct correlation with office and 24-hour systolic pressure
      (r=0.42 and 0.31, respectively), as well as with waist circumference (r=0.35, all
      P<0.001), but not with body mass index (r=0.10, P=not significant). Aortic pulse
      wave velocity was higher in the subgroup with the metabolic syndrome (10.0+/-2.7
      versus 8.8+/-2.1 m/s; P=0.003), whereas upper limb velocity did not differ in the
      2 groups (8.6+/-1.4 versus 8.7+/-1.5 m/s; P=not significant). In a multiple
      regression, aortic pulse wave velocity was independently associated with age,
      systolic blood pressure, and the metabolic syndrome. Only diastolic BP
      independently predicted upper limb pulse wave velocity. We conclude that in
      untreated hypertension, the metabolic syndrome is independently associated with a
      higher aortic, but not upper limb, pulse wave velocity. Central, but not general,
      adiposity is an important determinant of aortic stiffness in hypertension.

PMID- 15867140
TI  - Increased stroke volume and aortic stiffness contribute to isolated systolic
      hypertension in young adults.
AB  - Isolated systolic hypertension is a common condition in individuals aged older
      than 60 years. However, isolated systolic hypertension has also been described in
      young individuals, although the mechanisms are poorly understood. We hypothesized
      that in young adults, isolated systolic hypertension and essential hypertension
      have different hemodynamic mechanisms and the aim of this study was to test this
      hypothesis in a cohort of subjects from The ENIGMA Study. Peripheral and central
      blood pressure, aortic pulse wave velocity, cardiac output, stroke volume, and
      peripheral vascular resistance were determined in 1008 subjects, aged 17 to 27
      years. Compared with normotensive subjects, those with isolated systolic
      hypertension had significantly higher peripheral, central, and mean blood
      pressure, aortic pulse wave velocity, cardiac output, and stroke volume (P<0.001
      for all comparisons). However, there were no differences in pulse pressure
      amplification, heart rate, or peripheral vascular resistance between the two
      groups. Compared with subjects with essential hypertension, mean pressure, heart
      rate, and peripheral vascular resistance were all significantly lower in isolated
      systolic hypertensive subjects, but pulse pressure amplification, aortic pulse
      wave velocity, cardiac output, and stroke volume were higher (P<0.001 for all
      comparisons). We have demonstrated that in young adults, isolated systolic
      hypertension and essential hypertension arise from different hemodynamic
      mechanisms. Isolated systolic hypertension appears to result from an increased
      stroke volume and/or aortic stiffness, whereas the major hemodynamic abnormality
      underlying essential hypertension is an increased peripheral vascular resistance.
      Long-term follow-up of these individuals is now required to determine whether
      they are at increased risk compared with age-matched normotensive individuals.

PMID- 15867141
TI  - Renin-angiotensin system modulates oxidative stress-induced endothelial cell
      apoptosis in rats.
AB  - The role of the renin-angiotensin system in oxidative stress-induced apoptosis of
      endothelial cells (ECs) was investigated using a rat model and cultured ECs. EC
      apoptosis was induced by 5-minute intra-arterial treatment of a rat carotid
      artery with 0.01 mmol/L H2O2 and was evaluated at 24 hours by chromatin staining
      of en face specimens with Hoechst 33342. Although activity of angiotensin
      converting enzyme in arterial homogenates was not increased, administration of an
      angiotensin-converting enzyme inhibitor temocapril for 3 days before H2O2
      treatment inhibited EC apoptosis, followed by reduced neointimal formation 2
      weeks later. Also, an angiotensin II type 1 (AT1) receptor blocker (olmesartan)
      inhibited EC apoptosis, whereas angiotensin II administration accelerated
      apoptosis independently of blood pressure. Next, cultured ECs derived from a
      bovine carotid artery were treated with H2O2 to induce apoptosis, as evaluated by
      DNA fragmentation. Combination of angiotensin II and H2O2 dose-dependently
      increased EC apoptosis and 8-isoprostane formation, a marker of oxidative stress.
      Conversely, temocapril and olmesartan reduced apoptosis and 8-isoprostane
      formation induced by H2O2, suggesting that endogenous angiotensin II interacts
      with H2O2 to elevate oxidative stress levels and EC apoptosis. Neither an AT2
      receptor blocker, PD123319, affected H2O2-induced apoptosis, nor a NO synthase
      inhibitor, NG-nitro-L-arginine methyl ester, influenced the effect of temocapril
      on apoptosis in cell culture experiments. These results suggest that AT1 receptor
      signaling augments EC apoptosis in the process of oxidative stress-induced
      vascular injury.

PMID- 15867142
TI  - Basal NO locally modulates human iliac artery function in vivo.
AB  - We demonstrated previously that endogenous NO influences large-artery
      distensibility in the ovine hindlimb. However, the role of basal NO in larger
      human conduit arteries is controversial. The aim of this study was to investigate
      whether basal production of NO, acting locally, influences iliac artery
      distensibility in humans. Distensibility was assessed by intra-arterial
      measurement of the pulse wave velocity. Eighteen subjects, free of significant
      coronary or iliac artery disease, were studied after diagnostic cardiac
      catheterization. Simultaneous pressure waveforms were recorded with a high
      fidelity dual-pressure sensing catheter, placed in the common iliac artery during
      intra-arterial infusion of saline (baseline), glyceryl trinitrate (4 nmol/min),
      or NG-monomethyl-L-arginine (8 and 16 micromol/min). Drugs were infused
      proximally, via the catheter to perfuse the segment of artery under study, or
      distally, via the sheath, to control for any reflex changes in flow or
      sympathetic activation. Velocity was calculated using the foot-to-foot
      methodology. Six subjects received glyceryl trinitrate and 12 NG-monomethyl-L
      arginine. There was no change in velocity after infusion of glyceryl trinitrate
      or NG-monomethyl-L-arginine via the sheath. However, infusion of glyceryl
      trinitrate via the catheter significantly reduced velocity by 31.43+/-5.80%
      (mean+/-SEM; P<0.01; P=0.02 for comparison). Likewise, infusion of the highest
      dose of NG-monomethyl-L-arginine via the catheter significantly increased
      velocity by 27.25+/-8.20% (P=0.001; P=0.02 for comparison). Importantly, there
      was no change in mean arterial blood pressure throughout the studies. These data
      indicate that under resting conditions, local NO production modulates human iliac
      artery distensibility and that exogenous NO increases arterial distensibility.

PMID- 15867143
TI  - Aortic input impedance increases with age in healthy men and women.
AB  - Aortic input impedance represents the hydraulic load presented by the systemic
      circulation to the left ventricle of the heart and is increased in patients with
      cardiovascular disease. Aging is a strong independent risk factor for
      cardiovascular disease and could exert this effect partly through an increase in
      modulus of aortic input impedance. We used a novel noninvasive technique to
      determine aortic input impedance in 71 healthy men and women aged 20 to 69 years.
      We found that the aortic input impedance spectrum was shifted rightward with
      advancing age, characterized by a 37% increase in the frequency of the minimum
      modulus between the third and seventh decade (P<0.0001). The frequency of the
      minimum modulus correlated with age in all subjects (r=0.48; P<0.0001), in men
      (r=0.43; P<0.005), and in women (r=0.53; P=0.001). Although several physical
      characteristics were associated with the frequency of the minimum modulus
      (bivariate correlation), a regression model that included age and these physical
      characteristics showed that age was the only independent predictor of the
      frequency of the minimum modulus. We conclude that aortic input impedance
      increases with advancing age in healthy men and women. This increase in aortic
      input impedance may be an important mechanism by which age increases the risk of
      cardiovascular disease in humans.

PMID- 15867144
TI  - Estrogenic chemicals in plastic and oral contraceptives disrupt development of
      the fetal mouse prostate and urethra.
AB  - Exposure of human fetuses to man-made estrogenic chemicals can occur through
      several sources. For example, fetal exposure to ethinylestradiol occurs because
      each year approximately 3% of women taking oral contraceptives become pregnant.
      Exposure to the estrogenic chemical bisphenol A occurs through food and beverages
      because of significant leaching from polycarbonate plastic products and the
      lining of cans. We fed pregnant CD-1 mice ethinylestradiol (0.1 microg/kg per
      day) and bisphenol A (10 microg/kg per day), which are doses below the range of
      exposure by pregnant women. In male mouse fetuses, both ethinylestradiol and
      bisphenol A produced an increase in the number and size of dorsolateral prostate
      ducts and an overall increase in prostate duct volume. Histochemical staining of
      sections with antibodies to proliferating cell nuclear antigen and mouse keratin
      5 indicated that these increases were due to a marked increase in proliferation
      of basal epithelial cells located in the primary ducts. The urethra was malformed
      in the colliculus region and was significantly constricted where it enters the
      bladder, which could contribute to urine flow disorders. These effects were
      identical to those caused by a similar dose (0.1 microg/kg per day) of the
      estrogenic drug diethylstilbestrol (DES), a known human developmental teratogen
      and carcinogen. In contrast, a 2,000-fold higher DES dose completely inhibited
      dorsolateral prostate duct formation, revealing opposite effects of high and low
      doses of estrogen. Acceleration in the rate of proliferation of prostate
      epithelium during fetal life by small amounts of estrogenic chemicals could
      permanently disrupt cellular control systems and predispose the prostate to
      disease in adulthood.

PMID- 15867145
TI  - Inhibition of tumor growth by plant-derived mAb.
AB  - The tumor-associated antigen EpCAM (GA733-2) is a highly expressed target on
      adenocarcinoma cells, as defined by murine mAb CO17-1A. We recently developed a
      transgenic plant system for the safe and inexpensive production of large
      quantities of mAb CO17-1A as a future source of clinical-grade protein. Although
      the glycosylation pattern of plant-derived mAb (mAb(P)) CO17-1A differs
      considerably from that of the mammalian-derived mAb (mAb(M)), we show here that
      the biological activity of both mAbs is quite similar. mAb(P) heavy and light
      chains assembled to bind the recombinant antigen GA733-2E and specifically bound
      to human SW948 colorectal carcinoma cells expressing the antigen GA733-2 to the
      same extent as mAb(M). mAb(P) was as effective as mAb(M) CO17-1A in inhibiting
      tumor growth of xenotransplanted SW948 cells in nude mice. These results suggest
      the promise of transgenic plants as a useful alternative way to produce full-size
      mAb for cancer immunotherapy.

PMID- 15867146
TI  - Fine-mapping milk production quantitative trait loci on BTA6: analysis of the
      bovine osteopontin gene.
AB  - Bovine chromosome six (BTA6) harbors up to six quantitative trait loci (QTL)
      influencing the milk production of dairy cattle. In stark contrast to human,
      there is long-range linkage disequilibrium in dairy cattle, which has previously
      made it difficult to identify the mutations underlying these QTL. Using 38
      microsatellite markers in a pedigree of 3,147 Holstein bulls, we fine mapped
      regions of BTA6 that had previously been shown to harbor QTL. Next, we sequenced
      a 12.3-kb region harboring Osteopontin, a positional candidate for the
      statistically most significant of the identified QTL. Nine mutations were
      identified, and only genotypes for the OPN3907 indel were concordant with the QTL
      genotypes of eight bulls that were established by segregation analysis. Four of
      these mutations were genotyped, and a joint linkage/linkage disequilibrium
      mapping analysis was used to demonstrate the existence of only two functionally
      distinct clusters of haplotypes within the QTL region, which were uniquely
      defined by OPN3907 alleles. We estimate a probability of 0.40 that no other
      mutation within this region is concordant with the QTL genotypes of these eight
      bulls. Finally, we demonstrate that the motif harboring OPN3907, which is
      upstream of the promoter and within a region known to harbor tissue-specific
      osteopontin regulatory elements, is moderately conserved among mammals. The motif
      was not retrieved from database queries and may be a novel regulatory element.

PMID- 15867147
TI  - Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in
      a mouse model of type I diabetes.
AB  - The c-Jun NH(2)-terminal kinase isoform (JNK) 1 is implicated in type 2 diabetes.
      However, a potential role for the JNK2 protein kinase in diabetes has not been
      established. Here, we demonstrate that JNK2 may play an important role in type 1
      (insulin-dependent) diabetes that is caused by autoimmune destruction of beta
      cells. Studies of nonobese diabetic mice demonstrated that disruption of the
      Mapk9 gene (which encodes the JNK2 protein kinase) decreased destructive
      insulitis and reduced disease progression to diabetes. CD4(+) T cells from JNK2
      deficient nonobese diabetic mice produced less IFN-gamma but significantly
      increased amounts of IL-4 and IL-5, indicating polarization toward the Th2
      phenotype. This role of JNK2 to control the Th1/Th2 balance of the immune
      response represents a mechanism of protection against autoimmune diabetes. We
      conclude that JNK protein kinases may have important roles in diabetes, including
      functions of JNK1 in type 2 diabetes and JNK2 in type 1 diabetes.

PMID- 15867148
TI  - Lower bounds for moments of L-functions.
AB  - The moments of central values of families of L-functions have recently attracted
      much attention and, with the work of Keating and Snaith [(2000) Commun. Math.
      Phys. 214, 57-89 and 91-110], there are now precise conjectures for their
      limiting values. We develop a simple method to establish lower bounds of the
      conjectured order of magnitude for several such families of L-functions. As an
      example we work out the case of the family of all Dirichlet L-functions to a
      prime modulus.

PMID- 15867149
TI  - Evidence in vivo that the DEAD-box RNA helicase RhlB facilitates the degradation
      of ribosome-free mRNA by RNase E.
AB  - The RNA degradosome of Escherichia coli is a ribonucleolytic multienzyme complex
      containing RNase E, polynucleotide phosphorylase, RhlB, and enolase. Previous in
      vitro and in vivo work has shown that RhlB facilitates the exonucleolytic
      degradation of structured mRNA decay intermediates by polynucleotide
      phosphorylase in an ATPase-dependent reaction. Here, we show that deleting the
      gene encoding RhlB stabilizes a lacZ mRNA transcribed by bacteriophage T7 RNA
      polymerase. Deleting the gene encoding enolase has little if any effect. Other
      messages transcribed by T7 polymerase are also stabilized by DeltarhlB. The
      effect of point mutations inactivating RhlB is comparable with the effect of
      deleting the gene. Primer extension analysis of the lacZ message indicates that
      RhlB facilitates endoribonucleolytic cleavage by RNase E, demonstrating a
      functional interaction between the RNA helicase and the endoribonuclease. The
      possible physiological role of an RhlB-RNase E pathway and the mechanisms by
      which RhlB could facilitate RNase E cleavage are discussed.

PMID- 15867150
TI  - Deep history impacts present-day ecology and biodiversity.
AB  - Lizards and snakes putatively arose between the early Jurassic and late Triassic;
      they diversified worldwide and now occupy many different ecological niches,
      making them ideal for testing theories on the origin of ecological traits. We
      propose and test the "deep history hypothesis," which claims that differences in
      ecological traits among species arose early in evolutionary history of major
      clades, and that present-day assemblages are structured largely because of
      ancient, preexisting differences. We combine phylogenetic data with ecological
      data collected over nearly 40 years to reconstruct the evolution of dietary
      shifts in squamate reptiles. Data on diets of 184 lizard species in 12 families
      from 4 continents reveal significant dietary shifts at 6 major divergence points,
      reducing variation by 79.8%. The most striking dietary divergence (27.6%)
      occurred in the late Triassic, when Iguania and Scleroglossa split. These two
      clades occupy different regions of dietary niche space. Acquisition of chemical
      prey discrimination, jaw prehension, and wide foraging provided scleroglossans
      access to sedentary and hidden prey that are unavailable to iguanians. This
      cladogenic event may have profoundly influenced subsequent evolutionary history
      and diversification. We suggest the hypothesis that ancient events in squamate
      cladogenesis, rather than present-day competition, caused dietary shifts in major
      clades such that some lizard clades gained access to new resources, which in turn
      led to much of the biodiversity observed today.

PMID- 15867151
TI  - Calix[6]tren and copper(II): a third generation of funnel complexes on the way to
      redox calix-zymes.
AB  - Mono-copper enzymes play an important role in biology and their functionality is
      based on Cu(II)/Cu(I) redox processes. Modeling a mono-nuclear site remains a
      challenge for a better understanding of its intrinsic reactivity. The first
      member of a third generation of calixarene-based mono-copper "funnel" complexes
      is described. The ligand is a calix[6]arene capped by a tren unit, hence
      presenting a N(4) coordination site confined in a cavity. Its Cu(II) complexes
      were characterized by electronic and EPR spectroscopies. The x-ray structure of
      one of them shows a five-coordinated metal ion in a slightly distorted trigonal
      bipyramidal geometry thanks to its coordination to a guest ligand L (ethanol).
      The latter sits in the heart of the hydrophobic calixarene cone that mimics the
      active site chamber and the hydrophobic access channel of enzymes. Competitive
      binding experiments showed a preference order dimethylformamide > ethanol > MeCN
      for L binding at the single exchangeable metal site. Cyclic voltammetry studies
      showed irreversible redox processes in CH(2)Cl(2) when L is an oxygen donor
      caused by the redox-driven ejection of the guest at the Cu(I) level. In the
      presence of MeCN, a pseudoreversible process was obtained, owing to a fast
      equilibrium between a four and a five-coordinate Cu(I) species. Finally, a redox
      driven ligand interchange of dimethylformamide for MeCN at the Cu(I) state
      allowed the trapping of the thermodynamically less stable Cu(II)-MeCN adduct.
      Hence, this work represents an important step toward the elaboration of a
      functional supramolecular model for redox mono-copper enzymes, named redox calix
      zymes.

PMID- 15867152
TI  - Nonpolar solutes enhance water structure within hydration shells while reducing
      interactions between them.
AB  - The origins of the hydrophobic effect are widely thought to lie in structural
      changes of the water molecules surrounding a nonpolar solute. The spatial
      distribution functions of the water molecules surrounding benzene and cyclohexane
      computed previously from molecular dynamics simulations show a high density first
      hydration shell surrounding both solutes. In addition, benzene showed a strong
      preference for hydrogen bonding with two water molecules, one to each face of the
      benzene ring. The position data alone, however, do not describe the majority of
      orientational changes in the water molecules in the first hydration shells
      surrounding these solutes. In this paper, we measure the changes in orientation
      of the water molecules with respect to the solute through spatial orientation
      functions as well as radial/angular distribution functions. These data show that
      the water molecules hydrogen bonded to benzene have a strong orientation
      preference, whereas those around cyclohexane show a weaker tendency. In addition,
      the water-water interactions within and between the first two hydration shells
      were measured as a function of distance and "best" hydrogen bonding angle. Water
      molecules within the first hydration shell have increased hydrogen bonding
      structure; water molecules interacting across shell 1 and shell 2 have reduced
      hydrogen bonding structure.

PMID- 15867153
TI  - Holliday junction-binding peptides inhibit distinct junction-processing enzymes.
AB  - Holliday junctions (HJ) are the central intermediates in both homologous
      recombination and site-specific recombination performed by tyrosine recombinases
      such as the bacteriophage lambda Integrase (Int) protein. Previously, our lab
      identified peptide inhibitors of Int-mediated recombination that prevent the
      resolution of HJ intermediates. We now show that two of these inhibitors bind HJ
      DNA in the square-planar conformation even in the absence of Int protein. The
      peptides prevent unwinding of branched DNA substrates by the RecG helicase of
      Escherichia coli and interfere with the resolution of HJ substrates by the RuvABC
      complex. Our results suggest that these peptides target all proteins that process
      HJ in the square-planar conformation. These inhibitors should be extremely useful
      for dissecting homologous recombination and recombination-dependent repair in
      vitro and in vivo.

PMID- 15867154
TI  - Calculation of absolute protein-ligand binding free energy from computer
      simulations.
AB  - A general methodology for calculating the equilibrium binding constant of a
      flexible ligand to a protein receptor is formulated on the basis of potentials of
      mean force. The overall process is decomposed into several stages that can be
      computed separately: the free ligand in the bulk is first restrained into the
      conformation it adopts in the bound state, position, and orientation by applying
      biasing potentials, then it is translated into the binding site, where it is
      released completely. The conformational restraining potential is based on the
      root-mean-square deviation of the peptide coordinates relative to its average
      conformation in the bound complex. Free energy contributions from each stage are
      calculated by means of free energy perturbation potential of mean force
      techniques by using appropriate order parameters. The present approach avoids the
      need to decouple the ligand from its surrounding (bulk solvent and receptor
      protein) as is traditionally performed in the double-decoupling scheme. It is
      believed that the present formulation will be particularly useful when the
      solvation free energy of the ligand is very large. As an application, the
      equilibrium binding constant of the phosphotyrosine peptide pYEEI to the Src
      homology 2 domain of human Lck has been calculated. The results are in good
      agreement with experimental values.

PMID- 15867155
TI  - 5-Methyltetrahydrofolate and tetrahydrobiopterin can modulate electrotonically
      mediated endothelium-dependent vascular relaxation.
AB  - We have investigated the ability of 5-methyltetrahydrofolate (5-MTHF) and
      tetrahydrobiopterin (BH(4)) to modulate nitric oxide (NO)-independent vascular
      relaxations that are mediated by the sequential spread of endothelial
      hyperpolarization through the wall of the rabbit iliac artery by means of
      myoendothelial and homocellular smooth muscle gap junctions. Relaxations and
      subintimal smooth muscle hyperpolarizations evoked by cyclopiazonic acid were
      depressed by the gap junction inhibitor 2-aminoethoxydiphenyl borate, whose
      effects were prevented by 5-MTHF and BH(4), but not by their oxidized forms folic
      acid and 7,8-dihydrobiopterin. Analogously, 5-MTHF and BH(4), but not folic acid
      or 7,8-dihydrobiopterin, attenuated the depression of subintimal
      hyperpolarization by a connexin-mimetic peptide targeted against Cx37 and Cx40
      ((37,40)Gap 26) and the depression of subadventitial hyperpolarization by a
      peptide targeted against Cx43 ((43)Gap 26), thus reflecting the known
      differential expression of Cx37 and Cx40 in the endothelium and Cx43 in the media
      of the rabbit iliac artery. The inhibitory effects of 2-aminoethoxydiphenyl
      borate and (37,40)Gap 26 against subintimal hyperpolarization were prevented by
      catalase, which destroys H(2)O(2). 5-MTHF and BH(4) thus appear capable of
      modulating electrotonic signaling by means of myoendothelial and smooth muscle
      gap junctions by reducing oxidant stress, potentially conferring an ability to
      reverse the endothelial dysfunction found in disease states through mechanisms
      that are independent of NO.

PMID- 15867156
TI  - p130Rb2 and p27kip1 cooperate to control mobilization of angiogenic progenitors
      from the bone marrow.
AB  - Neoangiogenesis involves both bone marrow-derived myelomonocytic and endothelial
      progenitor cells as well as endothelial cells coopted from surrounding vessels.
      Cytokines induce these cells to proliferate, migrate, and exit the cell cycle to
      establish the vasculature; however, which cell cycle regulators play a role in
      these processes is largely unknown. Here, we report that mice lacking the cell
      cycle inhibitors p130 and p27 show defects in tumor neoangiogenesis, both in
      xenografts and spontaneously arising tumors. This defect is associated with
      impaired mobilization of endothelial and myelomonocytic angiogenic progenitors
      from the bone marrow. This article documents the role of these molecules in
      angiogenesis and further suggests that cell expansion and mobilization from the
      bone marrow of angiogenic precursors are separable events.

PMID- 15867157
TI  - Targeting c-Myc-activated genes with a correlation method: detection of global
      changes in large gene expression network dynamics.
AB  - This work studies the dynamics of a gene expression time series network. The
      network, which is obtained from the correlation of gene expressions, exhibits
      global dynamic properties that emerge after a cell state perturbation. The main
      features of this network appear to be more robust when compared with those
      obtained with a network obtained from a linear Markov model. In particular, the
      network properties strongly depend on the exact time sequence relationships
      between genes and are destroyed by random temporal data shuffling. We discuss in
      detail the problem of finding targets of the c-myc protooncogene, which encodes a
      transcriptional regulator whose inappropriate expression has been correlated with
      a wide array of malignancies. The data used for network construction are a time
      series of gene expression, collected by microarray analysis of a rat fibroblast
      cell line expressing a conditional Myc-estrogen receptor oncoprotein. We show
      that the correlation-based model can establish a clear relationship between
      network structure and the cascade of c-myc-activated genes.

PMID- 15867158
TI  - Chayanov revisited: a model for the economics of complex kin units.
AB  - Chayanov's model of the peasant economy is based on autarkic nuclear family
      households. Expansion to the more complex households and kin groups common in
      peasant societies shows that the sharp changes Chayanov observed in the
      consumer/producer ratio over the domestic cycle are smoothed by the
      intergenerational structure of complex households and extended kin groups. This
      amelioration may be retarded by competition between constituent units.
      Understanding the dynamics of the developmental cycle and micropolitics of
      domestic groups is a useful correction to Chayanov's widely used formulation,
      especially in developing countries where complex kin structures are common.

PMID- 15867159
TI  - Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced
      tauopathy and degeneration in vivo.
AB  - Neurofibrillary tangles composed of hyperphosphorylated, aggregated tau are a
      common pathological feature of tauopathies, including Alzheimer's disease.
      Abnormal phosphorylation of tau by kinases or phosphatases has been proposed as a
      pathogenic mechanism in tangle formation. To investigate whether kinase
      inhibition can reduce tauopathy and the degeneration associated with it in vivo,
      transgenic mice overexpressing mutant human tau were treated with the glycogen
      synthase kinase-3 (GSK-3) inhibitor lithium chloride. Treatment resulted in
      significant inhibition of GSK-3 activity. Lithium administration also resulted in
      significantly lower levels of phosphorylation at several epitopes of tau known to
      be hyperphosphorylated in Alzheimer's disease and significantly reduced levels of
      aggregated, insoluble tau. Administration of a second GSK-3 inhibitor also
      correlated with reduced insoluble tau levels, supporting the idea that lithium
      exerts its effect through GSK-3 inhibition. Levels of aggregated tau correlated
      strongly with degree of axonal degeneration, and lithium-chloride-treated mice
      showed less degeneration if administration was started during early stages of
      tangle development. These results support the idea that kinases are involved in
      tauopathy progression and that kinase inhibitors may be effective
      therapeutically.

PMID- 15867160
TI  - Engineering of protease variants exhibiting high catalytic activity and exquisite
      substrate selectivity.
AB  - The exquisite selectivity and catalytic activity of enzymes have been shaped by
      the effects of positive and negative selection pressure during the course of
      evolution. In contrast, enzyme variants engineered by using in vitro screening
      techniques to accept novel substrates typically display a higher degree of
      catalytic promiscuity and lower total turnover in comparison with their natural
      counterparts. Using bacterial display and multiparameter flow cytometry, we have
      developed a novel methodology for emulating positive and negative selective
      pressure in vitro for the isolation of enzyme variants with reactivity for
      desired novel substrates, while simultaneously excluding those with reactivity
      toward undesired substrates. Screening of a large library of random mutants of
      the Escherichia coli endopeptidase OmpT led to the isolation of an enzyme
      variant, 1.3.19, that cleaved an Ala-Arg peptide bond instead of the Arg-Arg bond
      preferred by the WT enzyme. Variant 1.3.19 exhibited greater than three million
      fold selectivity (-Ala-Arg-/-Arg-Arg-) and a catalytic efficiency for Ala-Arg
      cleavage that is the same as that displayed by the parent for the preferred
      substrate, Arg-Arg. A single amino acid Ser223Arg substitution was shown to
      recapitulate completely the unique catalytic properties of the 1.3.19 variant.
      These results can be explained by proposing that this mutation acts to "swap" the
      P(1) Arg side chain normally found in WT substrate peptides with the 223Arg side
      chain in the S(1) subsite of OmpT.

PMID- 15867161
TI  - Proof of physical exchange of genes on the chromosomes.
AB  - Seventy-five years ago, a convincing demonstration that the genes were physically
      aligned along the chromosome was lacking. Harriet Creighton (1909-2004) and
      Barbara McClintock (1902-1992) [Creighton, H. B. & McClintock, B. (1931) Proc.
      Natl. Acad. Sci. USA 17, 492-497] showed by an elegantly simple experiment in
      1931 that exchange between genes was accompanied by exchange of cytological,
      i.e., physical, parts of chromosomes. The work has been acclaimed as one of the
      great experiments in biology. Creighton's doctoral dissertation under
      McClintock's mentorship provided the basis for the landmark paper, which was
      unique in merging cytological with genetic data. A companion paper by McClintock,
      printed and bound back-to-back with the joint paper, set the essential stage with
      data on the cytological and genetic features that Creighton applied. Following
      directly from this work, and leading to today's recognition that the genome is a
      graspable entity, was the knowledge that the genes could be studied as components
      of a linear structure, the chromosome. Here, we review the data surrounding the
      Creighton and McClintock paper and provide a perspective on the significance of
      their findings.

PMID- 15867162
TI  - Postprocedural emboli in carotid artery stenting: where do they come from?

PMID- 15867163
TI  - In vitro models for assessing transcranial ultrasound-enhanced thrombolysis.

PMID- 15867164
TI  - Sex-based differences in response to recombinant tissue plasminogen activator in
      acute ischemic stroke.

PMID- 15867165
TI  - Diagnosing growth hormone deficiency after aneurysmal subarachnoid hemorrhage.

PMID- 15867166
TI  - Modern therapeutic approaches in the rehabilitation of walking ability after
      stroke.

PMID- 15867167
TI  - Oral anticoagulation in secondary prevention after cerebral ischemia of arterial
      origin.

PMID- 15867168
TI  - Peak oxygen consumption as a predictor of death in patients with heart failure
      receiving beta-blockers.
AB  - BACKGROUND: Peak oxygen uptake (peak VO2) is a strong predictor of mortality and
      is commonly used in the evaluation of patients for cardiac transplantation. Beta
      blockers reduce mortality in patients with heart failure, without influencing
      peak VO2, raising the possibility that peak VO2 is no longer suitable as an
      indicator of prognosis in these patients. METHODS AND RESULTS: We analyzed
      prospectively gathered data on 2105 patients referred for cardiopulmonary testing
      for all-cause mortality and for occurrence of death or transplantation. Patients
      receiving beta-blockers were younger, more likely to have coronary disease, and
      had a greater mean ejection fraction but had a similar peak VO2. There were 555
      deaths (26%) and 194 (9%) transplants during a median follow-up of 3.5 years.
      Peak VO2 was a predictor of mortality irrespective of beta-blocker use; a
      decrease of 1 mL x kg(-1) x min(-1) resulted in an adjusted hazard ratio (HR) of
      1.13 (95% CI 1.09 to 1.17, P<0.0001) in patients not receiving beta-blockers and
      1.27 (95% CI 1.18 to 1.36, P<0.0001) in patients receiving beta-blockers. Similar
      findings were noted when considering death or transplantation as an end point.
      Beta-blocker use was associated with better outcomes until peak VO2 values became
      very low (approximately 10 mL x kg(-1) x min(-1)), at which level survival rates
      were equally poor. CONCLUSION: Peak VO2 is a determinant of survival in patients
      in heart failure even in the setting of beta-blockade. Because of improved
      survival in patients treated with beta-blockers, the cut point value of 14 mg x
      kg(-1) x min(-1) for referral for cardiac transplantation in these patients
      requires reevaluation, and a lower cut point may be more appropriate.

PMID- 15867169
TI  - Effect of atorvastatin and irbesartan, alone and in combination, on postprandial
      endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic
      patients.
AB  - BACKGROUND: Postprandial hypertriglyceridemia and hyperglycemia are considered
      risk factors for cardiovascular disease. Evidence suggests that postprandial
      hypertriglyceridemia and hyperglycemia induce endothelial dysfunction and
      inflammation through oxidative stress. Statins and angiotensin type 1 receptor
      blockers have been shown to reduce oxidative stress and inflammation, improving
      endothelial function. METHODS AND RESULTS: Twenty type 2 diabetic patients ate 3
      different test meals: a high-fat meal, 75 g glucose alone, and a high-fat meal
      plus glucose. Glycemia, triglyceridemia, endothelial function, nitrotyrosine, C
      reactive protein, intercellular adhesion molecule-1, and interleukin-6 were
      assayed during the tests. Subsequently, diabetics took atorvastatin 40 mg/d,
      irbesartan 300 mg/d, both, or placebo for 1 week. The 3 tests were performed
      again between 5 and 7 days after the start of each treatment. High-fat load and
      glucose alone produced a decrease in endothelial function and increases in
      nitrotyrosine, C-reactive protein, intercellular adhesion molecule-1, and
      interleukin-6. These effects were more pronounced when high-fat load and glucose
      were combined. Short-term atorvastatin and irbesartan treatments significantly
      counterbalanced these phenomena, and their combination was more effective than
      either therapy alone. CONCLUSIONS: This study confirms an independent and
      cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on
      endothelial function and inflammation, suggesting oxidative stress as a common
      mediator of such an effect. Short-term treatment with atorvastatin and irbesartan
      may counterbalance this phenomenon; the combination of the 2 compounds is most
      effective.

PMID- 15867170
TI  - Postinfarction gene therapy against transforming growth factor-beta signal
      modulates infarct tissue dynamics and attenuates left ventricular remodeling and
      heart failure.
AB  - BACKGROUND: Fibrosis and progressive failure are prominent pathophysiological
      features of hearts after myocardial infarction (MI). We examined the effects of
      inhibiting transforming growth factor-beta (TGF-beta) signaling on post-MI
      cardiac fibrosis and ventricular remodeling and function. METHODS AND RESULTS: MI
      was induced in mice by left coronary artery ligation. An adenovirus harboring
      soluble TGF-beta type II receptor (Ad.CAG-sTbetaRII), a competitive inhibitor of
      TGF-beta, was then injected into the hindlimb muscles on day 3 after MI (control,
      Ad.CAG-LacZ). Post-MI survival was significantly improved among sTbetaRII-treated
      mice (96% versus control at 71%), which also showed a significant attenuation of
      ventricular dilatation and improved function 4 weeks after MI. At the same time,
      histological analysis showed reduced fibrous tissue formation. Although MI size
      did not differ in the 2 groups, MI thickness was greater and circumference was
      smaller in the sTbetaRII-treated group; within the infarcted area, alpha-smooth
      muscle actin-positive cells were abundant, which might have contributed to
      infarct contraction. Apoptosis among myofibroblasts in granulation tissue during
      the subacute stage (10 days after MI) was less frequent in the sTbetaRII-treated
      group, and sTbetaRII directly inhibited Fas-induced apoptosis in cultured
      myofibroblasts. Finally, treatment of MI-bearing mice with sTbetaRII was
      ineffective if started during the chronic stage (4 weeks after MI). CONCLUSIONS:
      Postinfarction gene therapy aimed at suppressing TGF-beta signaling mitigates
      cardiac remodeling by affecting cardiac fibrosis and infarct tissue dynamics
      (apoptosis inhibition and infarct contraction). This suggests that such therapy
      may represent a new approach to the treatment of post-MI heart failure,
      applicable during the subacute stage.

PMID- 15867172
TI  - Early onset and progression of left ventricular remodeling after alcohol septal
      ablation in hypertrophic obstructive cardiomyopathy.
AB  - BACKGROUND: Alcohol septal ablation (ASA) reduces left ventricular outflow tract
      (LVOT) pressure gradient in patients with hypertrophic obstructive cardiomyopathy
      (HOCM), which leads to left ventricular remodeling. We sought to describe the
      early to midterm changes and modulating factors of the remodeling process using
      cardiac MRI (CMR). METHODS AND RESULTS: CMR was performed at baseline and 1 and 6
      months after ASA in 29 patients with HOCM (age 52+/-16 years). Contrast-enhanced
      CMR showed no infarct-related hyperenhancement outside the target septal area.
      Septal mass decreased from 75+/-23 g at baseline to 68+/-22 and 58+/-19 g
      (P<0.001) at 1- and 6-month follow-up, respectively. Remote, nonseptal mass
      decreased from 141+/-41 to 132+/-40 and 111+/-27 g (P<0.001), respectively.
      Analysis of temporal trends revealed that septal mass reduction was positively
      associated with contrast-enhanced infarct size and transmural or left-sided
      septal infarct location at both 1 and 6 months. Remote mass reduction was
      associated with infarct location at 6 months but not with contrast-enhanced
      infarct size. By linear regression analysis, percentage remote mass reduction
      correlated significantly with LVOT gradient reduction at 6-month follow-up
      (P=0.03). CONCLUSIONS: Left ventricular remodeling after ASA occurs early and
      progresses on midterm follow-up, modulated by CMR infarct size and location.
      Remote mass reduction is associated with infarct location and correlates with
      reduction of the LVOT pressure gradient. Thus, myocardial hypertrophy in HOCM is,
      at least in part, afterload dependent and reversible and is not exclusively
      caused by the genetic disorder.

PMID- 15867171
TI  - Functional role of phosphodiesterase 3 in cardiomyocyte apoptosis: implication in
      heart failure.
AB  - BACKGROUND: Myocyte apoptosis plays an important role in pathological cardiac
      remodeling and the progression of heart failure. cAMP signaling is crucial in the
      regulation of myocyte apoptosis and cardiac remodeling. Multiple cAMP-hydrolyzing
      phosphodiesterases (PDEs), such as PDE3 and PDE4, coexist in cardiomyocytes and
      elicit differential temporal/spatial regulation of cAMP signaling. However, the
      role of PDE3 and PDE4 in the regulation of cardiomyocyte apoptosis remains
      unclear. Although chronic treatment with PDE3 inhibitors increases mortality in
      patients with heart failure, the contribution of PDE3 expression/activity in
      heart failure is not well known. METHODS AND RESULTS: In this study we report
      that PDE3A expression and activity were significantly reduced in human failing
      hearts as well as mouse hearts with chronic pressure overload. In primary
      cultured cardiomyocytes, chronic inhibition of PDE3 but not PDE4 activity by
      pharmacological agents or adenovirus-delivered antisense PDE3A promoted
      cardiomyocyte apoptosis. Both angiotensin II (Ang II) and the beta-adrenergic
      receptor agonist isoproterenol selectively induced a sustained downregulation of
      PDE3A expression and induced cardiomyocyte apoptosis. Restoring PDE3A via
      adenovirus-delivered expression of wild-type PDE3A1 completely blocked Ang II-
      and isoproterenol-induced cardiomyocyte apoptosis, suggesting the critical role
      of PDE3A reduction in cardiomyocyte apoptosis. Moreover, we defined a crucial
      role for inducible cAMP early repressor expression in PDE3A reduction-mediated
      cardiomyocyte apoptosis. CONCLUSIONS: Our results suggest that PDE3A reduction
      and consequent inducible cAMP early repressor induction are critical events in
      Ang II- and isoproterenol-induced cardiomyocyte apoptosis and may contribute to
      the development of heart failure. Drugs that maintain PDE3A function may
      represent an attractive therapeutic approach to treat heart failure.

PMID- 15867173
TI  - Association of prolonged QRS duration with death in a clinical trial of pacemaker
      therapy for sinus node dysfunction.
AB  - BACKGROUND: Prolonged QRS duration (QRSd) is an important prognostic indicator
      for death and heart failure hospitalization in patients with systolic heart
      failure. The relationship of baseline QRSd to death and heart failure
      hospitalization in patients with sinus node dysfunction who require pacemaker
      therapy is unknown. METHODS AND RESULTS: Baseline QRSd from 12-lead ECGs before
      pacemaker implantation were analyzed in the Mode Selection Trial (MOST), a 6
      year, 2010-patient randomized trial of dual-chamber versus ventricular pacing in
      sinus node dysfunction. Baseline QRSd was > or =120 ms in 23.4% of patients and
      was associated with older age, lower ejection fraction, cardiomyopathy, and prior
      heart failure. Adjusted Cox models demonstrated baseline QRSd > or =120 ms was a
      strong independent predictor of death (hazard ratio [95% CI] 1.35 [1.07, 1.70],
      P=0.010) but not heart failure hospitalization. The risk of death increased with
      increased QRSd from 60 to 120 ms (P=0.002 and hazard ratio [95% CI] 1.14 [1.05,
      1.23] for 10-ms increase in this range) after adjustment for other death
      predictors. CONCLUSIONS: Baseline QRSd > or =120 ms was associated with increased
      risk of death during pacemaker therapy for sinus node dysfunction.

PMID- 15867174
TI  - Role of gp91phox (Nox2)-containing NAD(P)H oxidase in angiogenesis in response to
      hindlimb ischemia.
AB  - BACKGROUND: Neovascularization is potentially important for the treatment of
      ischemic heart and limb disease. We reported that reactive oxygen species (ROS)
      derived from gp91phox (Nox2)-containing NAD(P)H oxidase are involved in
      angiogenesis in mouse sponge models as well as in vascular endothelial growth
      factor (VEGF) signaling in cultured endothelial cells. The role of gp91phox
      derived ROS in neovascularization in response to tissue ischemia is unknown,
      however. METHODS AND RESULTS: Here, we show that neovascularization in the
      ischemic hindlimb is significantly impaired in gp91phox-/- mice as compared with
      wild-type (WT) mice as evaluated by laser Doppler flow, capillary density, and
      microsphere measurements. In WT mice, inflammatory cell infiltration in the
      ischemic hindlimb was maximal at 3 days, whereas capillary formation was
      prominent at 7 days when inflammatory cells were no longer detectable. Increased
      O2*- production and gp91phox expression were present at both time points. The
      dihydroethidium staining of ischemic tissues indicates that O2*- is mainly
      produced from inflammatory cells at 3 days and from neovasculature at 7 days
      after operation. Relative to WT mice, ischemia-induced ROS production in gp91phox
      /- mice at both 3 and 7 days was diminished, whereas VEGF expression was enhanced
      and the inflammatory response was unchanged. Infusion of the antioxidant ebselen
      into WT mice also significantly blocked the increase in blood flow recovery and
      capillary density after ischemia. CONCLUSIONS: gp91phox-derived ROS play an
      important role in mediating neovascularization in response to tissue ischemia.
      NAD(P)H oxidases and their products are potential therapeutic targets for
      regulating angiogenesis in vivo.

PMID- 15867175
TI  - Enrichment of genes in the aortic intima that are associated with stratified
      epithelium: implications of underlying biomechanical and barrier properties of
      the arterial intima.
AB  - BACKGROUND: Arteries and veins are exposed to different pressures and are easily
      distinguished by morphology. Although several recent studies have focused on
      differential gene expression between the arterial and venous endothelium, the
      molecular distinctions that give rise to the dramatic structural distinctions
      between arteries and veins, such as in the organization of the intima, are not
      known. METHODS AND RESULTS: We used high-density oligonucleotide arrays to
      analyze the transcriptional profile of the mouse aorta and inferior vena cava
      (IVC), not restricting our analysis to the endothelium, to identify genes whose
      expression was enriched in aorta over other tissues and the IVC. By quantitative
      reverse transcription-polymerase chain reaction analysis, these genes have been
      shown to be highly expressed in the mouse aorta and were either expressed at low
      levels or were undetectable in the murine IVC. By immunofluorescence analysis of
      human tissue, we determined that a subset of these aorta-enriched proteins
      exhibited a primarily intima-restricted expression. Intimal expression of at
      least a subset of these genes, plakoglobin, galectin 7, sciellin, and SPRR3, was
      also detected in other types of arteries but not in veins. Furthermore, SPRR3
      expression in the intima was primarily associated with atheromas. The proteins
      identified are functionally related in that they are known to also be enriched in
      stratified epithelia, where they play an important role in stress-bearing and
      barrier properties. CONCLUSIONS: Vascular expression of these genes has not been
      reported previously. Our observations suggest that they may play a significant
      role in the mechanisms by which large arteries may adapt to biomechanical stress.

PMID- 15867176
TI  - Transgenic rabbit model for human troponin I-based hypertrophic cardiomyopathy.
AB  - BACKGROUND: Transgenic and gene-targeted models have focused on the mouse.
      Fundamental differences between the mouse and human exist in Ca2+ handling during
      contraction/relaxation and in alterations in Ca2+ flux during heart failure, with
      the rabbit more accurately reflecting the human system. METHODS AND RESULTS:
      Cardiac troponin I (cTnI) mutations can cause familial hypertrophic
      cardiomyopathy. An inhibitory domain mutation, arginine146-->glycine
      (cTnI(146Gly)), was modeled with the use of transgenic expression in the rabbit
      ventricle. cTnI(146Gly) levels >40% of total cTnI were perinatally lethal,
      whereas replacement levels of 15% to 25% were well tolerated. cTnI(146Gly)
      expression led to a leftward shift in the force-pCa2+ curves with cardiomyocyte
      disarray, fibrosis, and altered connexin43 organization. In isolated cTnI(146Gly)
      myocytes, twitch relaxation amplitudes were smaller than in normal cells, but
      [Ca]i transients and sarcoplasmic reticulum Ca2+ load were not different.
      Detrended fluctuation analysis of the QT(max) intervals was used to evaluate the
      cardiac repolarization phase and showed a significantly higher scaling exponent
      in the transgenic animals. CONCLUSIONS: Expression of modest amounts of
      cTnI(146Gly) led to subtle defects without severely affecting cardiac function.
      Aberrant connexin organization, subtle morphological deficits, and an altered
      fractal pattern of the repolarization phase of transgenic rabbits, in the absence
      of entropy or other ECG abnormalities, may indicate an early developing pathology
      before the onset of more obvious repolarization abnormalities or major
      alterations in cardiac mechanics.

PMID- 15867177
TI  - Forced expression of alpha-myosin heavy chain in the rabbit ventricle results in
      cardioprotection under cardiomyopathic conditions.
AB  - BACKGROUND: The biochemical differences between the 2 mammalian cardiac myosin
      heavy chains (MHCs), alpha-MHC and beta-MHC, are well described, but the
      physiological consequences of basal isoform expression and isoform shifts in
      response to altered cardiac load are not clearly understood. Mature human
      ventricle contains primarily the beta-MHC isoform. However, the alpha-MHC isoform
      can be detected in healthy human ventricle and appears to be significantly
      downregulated in failing hearts. The unique biochemical properties of the alpha
      MHC isoform might offer functional advantages in a failing heart that is
      expressing only the beta-MHC isoform. This hypothesis cannot be tested in mice or
      rats because both species express alpha-MHC as the predominant isoform. METHODS
      AND RESULTS: To test the effects of persistent alpha-MHC expression on the
      background of beta-MHC, we made transgenic (TG) rabbits that expressed rabbit
      alpha-MHC cDNA in the ventricle so that the endogenous myosin was partially
      replaced by the transgenically encoded species. Molecular, histological, and
      functional analyses showed no significant baseline effects in the TG rabbits
      compared with nontransgenic (NTG) littermates. To determine whether alpha-MHC
      expression afforded any advantages to stressed myocardium, a cohort of TG and NTG
      rabbits was subjected to rapid ventricular pacing. Although both the TG and NTG
      rabbits developed dilated cardiomyopathy, the TG rabbits had a higher shortening
      fraction, less septal thinning, and more normal +/-dP/dt than paced NTG rabbits.
      CONCLUSIONS: Transgenic expression of alpha-MHC does not have any apparent
      detrimental effects under basal conditions and is cardioprotective in
      experimental tachycardia-induced cardiomyopathy.

PMID- 15867178
TI  - Elevated blood pressure linked to primary hyperaldosteronism and impaired
      vasodilation in BK channel-deficient mice.
AB  - BACKGROUND: Abnormally elevated blood pressure is the most prevalent risk factor
      for cardiovascular disease. The large-conductance, voltage- and Ca2+-dependent K+
      (BK) channel has been proposed as an important effector in the control of
      vascular tone by linking membrane depolarization and local increases in cytosolic
      Ca2+ to hyperpolarizing K+ outward currents. However, the BK channel may also
      affect blood pressure by regulating salt and fluid homeostasis, particularly by
      adjusting the renin-angiotensin-aldosterone system. METHODS AND RESULTS: Here we
      report that deletion of the pore-forming BK channel alpha subunit leads to a
      significant blood pressure elevation resulting from hyperaldosteronism
      accompanied by decreased serum K+ levels as well as increased vascular tone in
      small arteries. In smooth muscle from small arteries, deletion of the BK channel
      leads to a depolarized membrane potential, a complete lack of membrane
      hyperpolarizing spontaneous K+ outward currents, and an attenuated cGMP
      vasorelaxation associated with a reduced suppression of Ca2+ transients by cGMP.
      The high level of BK channel expression observed in wild-type adrenal glomerulosa
      cells, together with unaltered serum renin activities and corticotropin levels in
      mutant mice, suggests that the hyperaldosteronism results from abnormal adrenal
      cortical function in BK(-/-) mice. CONCLUSIONS: These results identify previously
      unknown roles of BK channels in blood pressure regulation and raise the
      possibility that BK channel dysfunction may underlie specific forms of
      hyperaldosteronism.

PMID- 15867179
TI  - Contributions of depressive mood and circulating inflammatory markers to coronary
      heart disease in healthy European men: the Prospective Epidemiological Study of
      Myocardial Infarction (PRIME).
AB  - BACKGROUND: Data on the possible association between depressive disorders and
      inflammatory markers are scarce and inconsistent. We investigated whether
      subjects with depressive mood had higher levels of a wide range of inflammatory
      markers involved in coronary heart disease (CHD) incidence and examined the
      contribution of these inflammatory markers and depressive mood to CHD outcome.
      METHODS AND RESULTS: We built a nested case-referent study within the Prospective
      Epidemiological Study of Myocardial Infarction (PRIME) study of healthy middle
      aged men from Belfast and France. We considered the baseline plasma sample from
      335 future cases (angina pectoris, nonfatal myocardial infarction, coronary
      death) and 670 matched controls (2 controls per case). Depressive mood
      characterized men whose baseline depression score (13-item modification of the
      Welsh depression subscale) was in the fourth quartile (mean score, 5.75; range, 4
      to 12). On average, men with depressive mood had 46%, 16%, and 10% higher C
      reactive protein, interleukin-6, and intercellular adhesion molecule-1 levels,
      respectively, independently of case-control status, social characteristics, and
      classic cardiovascular risk factors; no statistical difference was found for
      fibrinogen. The odds ratios of depressive mood for CHD were 1.35 (95% CI, 1.05 to
      1.73) in univariate analysis and 1.50 (95% CI, 1.04 to 2.15) after adjustment for
      social characteristics and classic cardiovascular risk factors. The latter odds
      ratio remained unchanged when each inflammatory marker was added separately, and
      in this analysis, each inflammatory marker contributed significantly to CHD event
      risk. CONCLUSIONS: These data support an association of depressive mood with
      inflammatory markers and suggest that depressive mood is related to CHD even
      after adjustment for these inflammatory markers.

PMID- 15867180
TI  - Female mice lacking estrogen receptor beta display prolonged ventricular
      repolarization and reduced ventricular automaticity after myocardial infarction.
AB  - BACKGROUND: Major gender-based differences in the incidence of ventricular
      tachyarrhythmia after myocardial infarction have been shown in humans. Although
      the underlying mechanisms are unclear, earlier studies suggest that estrogen
      receptor-mediated effects play a major role in this process. METHODS AND RESULTS:
      We examined the effect of estrogen receptor alpha (ERalpha) and estrogen receptor
      beta (ERbeta) on the electrophysiological phenotype in female mice with and
      without chronic anterior myocardial infarction. There was no significant
      difference in overall mortality, infarct size, and parameters of left ventricular
      remodeling when we compared infarcted ERalpha-deficient and ERbeta-deficient mice
      with infarcted wild-type animals. In the 12-hour telemetric ECG recording 6 weeks
      after myocardial infarction, surface ECG parameters did not show significant
      differences in comparisons of ERalpha-deficient mice versus wild-type controls,
      infarcted versus noninfarcted ERalpha-deficient mice, and infarcted ERalpha
      deficient versus infarcted wild-type mice. However, infarcted ERbeta-deficient
      versus noninfarcted ERbeta-deficient mice showed a significant prolongation of
      the QT (61+/-6 versus 48+/-8 ms; P<0.05) and QTc intervals (61+/-7 versus 51+/-9
      ms; P<0.05) and the JT (42+/-6 versus 31+/-4 ms; P<0.05) and JTc intervals (42+/
      7 versus 33+/-4 ms; P<0.05). Furthermore, infarcted ERbeta-deficient versus
      infarcted wild-type mice showed a significant prolongation of the QT (61+/-6
      versus 53+/-8 ms; P<0.05) and QTc intervals (61+/-7 versus 53+/-7 ms; P<0.05) and
      the JT (42+/-6 versus 31+/-5 ms; P<0.05) and JTc intervals (42+/-7 versus 31+/-5
      ms; P<0.05), accompanied by a significant decrease of ventricular premature beats
      (7+/-21/h versus 71+/-110/h; P<0.05). Finally, real-time polymerase chain
      reaction-based quantitative analysis of mRNA levels showed a significantly lower
      expression of Kv4.3 (coding for I(to)) in ERbeta-deficient mice (P<0.05).
      CONCLUSIONS: Estrogen receptor beta deficiency results in prolonged ventricular
      repolarization and decreased ventricular automaticity in female mice with chronic
      myocardial infarction.

PMID- 15867181
TI  - Simvastatin versus ezetimibe: pleiotropic and lipid-lowering effects on
      endothelial function in humans.
AB  - BACKGROUND: Statins may exert important pleiotropic effects, ie, improve
      endothelial function, independently of their impact on LDL cholesterol. In
      humans, however, pleiotropic effects of statins have never been unequivocally
      demonstrated because prolonged statin treatment always results in reduced LDL
      cholesterol levels. We therefore tested the hypothesis that similar reductions in
      LDL cholesterol with simvastatin and ezetimibe, a novel cholesterol absorption
      inhibitor, result in different effects on endothelial function. METHODS AND
      RESULTS: Twenty patients with chronic heart failure were randomized to 4 weeks of
      simvastatin (10 mg/d) or ezetimibe (10 mg/d) treatment. Flow-dependent dilation
      (FDD) of the radial artery was determined by high-resolution ultrasound before
      and after intra-arterial vitamin C to determine the portion of FDD inhibited by
      radicals (DeltaFDD-VC). Activity of extracellular superoxide dismutase, a major
      vascular antioxidant enzyme system, was determined after release from the
      endothelium by a heparin bolus injection. Endothelial progenitor cells were
      analyzed with an in vitro assay. Simvastatin and ezetimibe treatment reduced LDL
      cholesterol to a similar extent (15.6% versus 15.4%; P=NS), whereas changes in
      mevalonate, the product of HMG-CoA-reductase, differed between groups
      (Deltamevalonate-simvastatin, -1.04+/-0.62 versus Deltamevalonate-ezetimibe,
      1.79+/-0.94 ng/mL; P<0.05 between groups). Importantly, FDD was markedly improved
      after simvastatin (10.5+/-0.6% versus 5.1+/-0.7%; P<0.01) but not after ezetimibe
      treatment (5.6+/-0.5% versus 5.8+/-0.6%; P=NS). DeltaFDD-VC was substantially
      reduced after simvastatin but not after ezetimibe treatment. Extracellular
      superoxide dismutase activity was increased by >100% (P<0.05) after simvastatin
      but not ezetimibe treatment. Simvastatin treatment increased the number of
      functionally active endothelial progenitor cells, whereas ezetimibe had no
      effect. CONCLUSIONS: Four weeks of simvastatin treatment improves endothelial
      function independently of LDL cholesterol lowering, at least in part by reducing
      oxidant stress. Simvastatin may thereby exert important pleiotropic effects in
      humans.

PMID- 15867182
TI  - Lower serum sodium is associated with increased short-term mortality in
      hospitalized patients with worsening heart failure: results from the Outcomes of
      a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart
      Failure (OPTIME-CHF) study.
AB  - BACKGROUND: The prognostic value of serum sodium in patients hospitalized for
      worsening heart failure has not been well defined. METHODS AND RESULTS: The
      Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of
      Chronic Heart Failure (OPTIME-CHF) study randomized 949 patients with systolic
      dysfunction hospitalized for worsening heart failure to receive 48 to 72 hours of
      intravenous milrinone or placebo in addition to standard therapy. In a
      retrospective analysis, we investigated the relationship between admission serum
      sodium and the primary end point of days hospitalized for cardiovascular causes
      within 60 days of randomization, as well as the secondary end points of in
      hospital mortality, 60-day mortality, and 60-day mortality/rehospitalization. The
      number of days hospitalized for cardiovascular causes was higher in the lowest
      sodium quartile: 8.0 (4.5, 18.5) versus 6 (4, 13) versus 6 (4, 11.5) versus 6 (4,
      12) days (P<0.015 for comparison with the lowest quartile). Lower serum sodium
      was associated with higher in-hospital and 60-day mortality: 5.9% versus 1%
      versus 2.3% versus 2.3% (P<0.015) and 15.9% versus 6.4% versus 7.8% versus 7%
      (P=0.002), respectively. There was a trend toward higher
      mortality/rehospitalization for patients who were in the lowest sodium quartile.
      Multivariable-adjusted Cox proportional hazards analysis showed that serum sodium
      on admission, when modeled linearly, predicted increased 60-day mortality: sodium
      (per 3-mEq/L decrease) had a hazard ratio of 1.18 with a 95% CI of 1.03 to 1.36
      (P=0.018). CONCLUSIONS: In patients hospitalized for worsening heart failure,
      admission serum sodium is an independent predictor of increased number of days
      hospitalized for cardiovascular causes and increased mortality within 60 days of
      discharge.

PMID- 15867183
TI  - p38 MAP kinase mediates inflammatory cytokine induction in cardiomyocytes and
      extracellular matrix remodeling in heart.
AB  - BACKGROUND: Increasing evidence suggests that development of heart failure
      involves activation of stress-response inflammatory cytokines, including tumor
      necrosis factor-alpha and interleukin-6. Yet, the myocyte contribution to their
      induction in failing hearts and the underlying regulatory mechanism in stressed
      myocardium remain unclear. METHODS AND RESULTS: In cultured cardiac myocytes,
      specific activation of stress-activated mitogen-activated protein kinase, p38, by
      upstream activator MKK6bE led to significant induction of tumor necrosis factor
      alpha and interleukin-6 secretion, whereas treating cells with a selective p38
      inhibitor (SB239068) significantly blocked the cytokine secretion from myocytes
      and increased their intracellular accumulation. Targeted expression of MKK6bE in
      transgenic hearts also resulted in a marked elevation in plasma tumor necrosis
      factor-alpha and interleukin-6; oral administration of SB239068 resulted in a
      significant reduction in their plasma levels but an increase in intracardiac
      accumulation of both cytokines. MKK6bE transgenic hearts developed marked
      interstitial fibrosis with increased matrix metalloproteinase abundance and
      selective induction of tissue inhibitor of matrix metalloproteinase-1; this
      extracellular matrix remodeling was also significantly attenuated by p38
      inhibition. Along with cytokine induction and extracellular remodeling, MKK6bE
      transgenic animals displayed impaired hemodynamic function, whereas p38
      inhibition improved the cardiac performance and prolonged the survival of the
      animals. CONCLUSIONS: Stress-activated p38 kinase is a critical regulator of
      inflammatory response in cardiomyocytes with significant contribution to
      pathological remodeling in stressed myocardium. Inhibition of p38 may represent a
      useful therapeutic avenue to ameliorate cardiac pathology and heart failure
      evolution.

PMID- 15867184
TI  - Effect of intensive glycemic control on levels of markers of inflammation in type
      1 diabetes mellitus in the diabetes control and complications trial.
AB  - BACKGROUND: Type 1 diabetes mellitus is associated with an increased risk of
      cardiovascular disease (CVD) that is not fully explained by conventional risk
      factors. The Diabetes Control and Complications Trial (DCCT) showed that
      intensive diabetes therapy reduced levels of LDL cholesterol and triglycerides
      but increased the risk of major weight gain, which might adversely affect CVD
      risk. The present study examined the effect of intensive therapy on levels of
      several markers of inflammation that have been linked to risk of CVD. METHODS AND
      RESULTS: We measured levels of inflammatory biomarkers in stored baseline and 3
      year follow-up serum specimens from a random sample of 385 participants in the
      DCCT, a multicenter trial in which 1441 subjects aged 13 to 39 years with type 1
      diabetes mellitus were randomized to intensive or conventional diabetes
      treatment. The markers included high-sensitivity C-reactive protein (hsCRP),
      soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell
      adhesion molecule type 1 (sVCAM-1), and the 55-kDa soluble tumor necrosis factor
      alpha receptor 1 (sTNF-R1). We examined the effect of intensive therapy on the
      change in levels of the inflammatory markers. In unadjusted analyses, levels of
      hsCRP and sTNF-R1 increased in both treatment groups after 3 years of follow-up,
      with no significant difference between groups for hsCRP (P=0.53) but with a
      greater increase of sTNF-R1 in the intensive therapy group (P=0.002). In
      contrast, mean levels of sICAM-1 and sVCAM-1 decreased among participants
      assigned to intensive therapy, whereas they did not change among those in the
      conventional treatment group (P=0.03 for sICAM-1; P=0.03 for sVCAM-1). After
      adjustment for baseline levels and other factors, intensive therapy remained
      associated with a significant decrease in sICAM-1 (P=0.02) and an increase in
      sTNF-R1 (P=0.03). For hsCRP, there was a significant interaction between the top
      third of weight gain and treatment assignment (P=0.03). In subgroup analyses
      among subjects undergoing intensive therapy, hsCRP levels increased among those
      who gained the most weight, whereas it decreased among those in the bottom third
      of weight gain (P=0.0004). CONCLUSIONS: Intensive therapy in patients with type 1
      diabetes mellitus reduced levels of sICAM-1 and increased levels of sTNF-R1 and
      of hsCRP among those who gained weight. These data demonstrate that the effect of
      intensive therapy on inflammation is complex and, to the extent that hsCRP is a
      risk factor, suggest that the risk of atherosclerosis among diabetic patients may
      be influenced by the degree of weight gain while undergoing intensive therapy.

PMID- 15867185
TI  - Long-term results of mitral valve repair in active endocarditis.
AB  - BACKGROUND: Several investigators have reported the feasibility of mitral valve
      repair in active endocarditis, but the long-term results are still unknown.
      METHODS AND RESULTS: We reviewed 37 consecutive patients who underwent mitral
      valve repair with the Carpentier technique for active endocarditis in our center
      between 1989 and 1994. This repair involved prosthetic annuloplasty in 31
      patients (84%), valve resection in 31 (84%), chordal shortening or transposition
      in 19 (51%), pericardial patch in 16 (43%), and direct suture of leaflet
      perforation in 4 (11%). Associated procedures were primarily aortic valve repair
      or replacement in 11 (30%) and tricuspid repair in 2 (6%). Early complications
      included 1 operative death (3%; 95% CI, 0 to 15.5) and 1 reoperation for
      pericardial patch dehiscence. Recurrence of endocarditis was observed in 1
      patient (3%; 95% CI, 0 to 16). The 10-year survival rate and freedom from mitral
      valve reoperation were 80% (95% CI, 66 to 94) and 91% (95% CI, 81 to 100),
      respectively. At 10 years, most patients (96%) were in good functional status
      (NYHA class I to II) with no or trivial mitral regurgitation (92%) on
      echocardiography. CONCLUSIONS: Mitral valve repair using Carpentier's techniques
      in patients with active endocarditis offers very good long-term results with a
      low rate of recurrence or reoperation.

PMID- 15867186
TI  - Controversies in antiplatelet therapy for patients with cardiovascular disease.

PMID- 15867187
TI  - Images in cardiovascular medicine. Traumatic coronary artery fistula in a child.

PMID- 15867188
TI  - Letter regarding article by Rosenhek et al, "statins but not angiotensin
      converting enzyme inhibitors delay progression of aortic stenosis".

PMID- 15867189
TI  - Letter regarding article by Masoudi et al, "national patterns of use and
      effectiveness of angiotensin-converting enzyme inhibitors in older patients with
      heart failure and left ventricular systolic dysfunction".

PMID- 15867190
TI  - Letter regarding article by Kaufmann et al, "systemic inhibition of nitric oxide
      synthase unmasks neural constraint of maximal myocardial blood flow in humans".

PMID- 15867191
TI  - Use of heart valves in older patients.

PMID- 15867192
TI  - Percutaneous mitral valve repair: are they changing the guard?

PMID- 15867193
TI  - Molecular basis of restenosis and drug-eluting stents.

PMID- 15867194
TI  - Studies on Escherichia coli RNase P RNA with Zn2+ as the catalytic cofactor.
AB  - We demonstrate, for the first time, catalysis by Escherichia coli ribonuclease P
      (RNase P) RNA with Zn2+ as the sole divalent metal ion cofactor in the presence
      of ammonium, but not sodium or potassium salts. Hill analysis suggests a role for
      two or more Zn2+ ions in catalysis. Whereas Zn2+ destabilizes substrate ground
      state binding to an extent that precludes reliable Kd determination, Co(NH3)6(3+)
      and Sr2+ in particular, both unable to support catalysis by themselves, promote
      high-substrate affinity. Zn2+ and Co(NH3)6(3+) substantially reduce the fraction
      of precursor tRNA molecules capable of binding to RNase P RNA. Stimulating and
      inhibitory effects of Sr2+ on the ribozyme reaction with Zn2+ as cofactor could
      be rationalized by a model involving two Sr2+ ions (or two classes of Sr2+ ions).
      Both ions improve substrate affinity in a cooperative manner, but one of the two
      inhibits substrate conversion in a non-competitive mode with respect to the
      substrate and the Zn2+. A single 2'-fluoro modification at nt -1 of the substrate
      substantially weakened the inhibitory effect of Sr2+. Our results demonstrate
      that the studies on RNase P RNA with metal cofactors other than Mg2+ entail
      complex effects on structural equilibria of ribozyme and substrate RNAs as well
      as E*S formation apart from the catalytic performance.

PMID- 15867195
TI  - Activity of Lac repressor anchored to the Escherichia coli inner membrane.
AB  - The transient inactivation of gene regulatory proteins by their sequestration to
      the cytoplasmic membrane in response to cognate signals is an increasingly
      recognized mechanism of gene regulation in bacteria. It remained to be shown,
      however, whether tethering to the membrane per se could be responsible for
      inactivation, i.e. whether such relocation leads to a spatial separation from the
      chromosome that results in inactivity or whether other mechanisms are involved.
      We, therefore, investigated the activity of Lac repressor artificially attached
      to the Escherichia coli cytoplasmic membrane. We demonstrate that this chimeric
      protein perfectly represses transcription initiated at the tac operator-promoter
      present on a plasmid and even in the chromosome. Moreover, this repression is
      inducible as normal. The data suggest that proteins localized to the inner face
      of the cytoplasmic membrane in principle have unrestricted access to the
      chromosome. Thus sequestration to the membrane in terms of physical separation
      from the chromosome cannot account alone for the inactivation of regulatory
      proteins. Other mechanisms, like induction of a conformational change or masking
      of binding domains are required additionally.

PMID- 15867196
TI  - XRCC1 is required for DNA single-strand break repair in human cells.
AB  - The X-ray repair cross complementing 1 (XRCC1) protein is required for viability
      and efficient repair of DNA single-strand breaks (SSBs) in rodents. XRCC1
      deficient mouse or hamster cells are hypersensitive to DNA damaging agents
      generating SSBs and display genetic instability after such DNA damage. The
      presence of certain polymorphisms in the human XRCC1 gene has been associated
      with altered cancer risk, but the role of XRCC1 in SSB repair (SSBR) in human
      cells is poorly defined. To elucidate this role, we used RNA interference to
      modulate XRCC1 protein levels in human cell lines. A reduction in XRCC1 protein
      levels resulted in decreased SSBR capacity as measured by the comet assay and
      intracellular NAD(P)H levels, hypersensitivity to the cell killing effects of the
      DNA damaging agents methyl methanesulfonate (MMS), hydrogen peroxide and ionizing
      radiation and enhanced formation of micronuclei following exposure to MMS.
      Lowered XRCC1 protein levels were also associated with a significant delay in S
      phase progression after exposure to MMS. These data clearly demonstrate that
      XRCC1 is required for efficient SSBR and genomic stability in human cells.

PMID- 15867197
TI  - Nebulon: a system for the inference of functional relationships of gene products
      from the rearrangement of predicted operons.
AB  - Since operons are unstable across Prokaryotes, it has been suggested that perhaps
      they re-combine in a conservative manner. Thus, genes belonging to a given operon
      in one genome might re-associate in other genomes revealing functional
      relationships among gene products. We developed a system to build networks of
      functional relationships of gene products based on their organization into
      operons in any available genome. The operon predictions are based on inter-genic
      distances. Our system can use different kinds of thresholds to accept a
      functional relationship, either related to the prediction of operons, or to the
      number of non-redundant genomes that support the associations. We also work by
      shells, meaning that we decide on the number of linking iterations to allow for
      the complementation of related gene sets. The method shows high reliability
      benchmarked against knowledge-bases of functional interactions. We also
      illustrate the use of Nebulon in finding new members of regulons, and of other
      functional groups of genes. Operon rearrangements produce thousands of high
      quality new interactions per prokaryotic genome, and thousands of confirmations
      per genome to other predictions, making it another important tool for the
      inference of functional interactions from genomic context.

PMID- 15867198
TI  - ABL mutations in late chronic phase chronic myeloid leukemia patients with up
      front cytogenetic resistance to imatinib are associated with a greater likelihood
      of progression to blast crisis and shorter survival: a study by the GIMEMA
      Working Party on Chronic Myeloid Leukemia.
AB  - PURPOSE: Point mutations within the ABL kinase domain of the BCR-ABL gene have
      been associated with clinical resistance to imatinib mesylate in chronic myeloid
      leukemia (CML) patients. To shed further light on the frequency, distribution,
      and prognostic significance of ABL mutations, we retrospectively analyzed a
      homogeneous cohort of late chronic phase CML patients who showed primary
      cytogenetic resistance to imatinib. PATIENTS AND METHODS: Using denaturing high
      performance liquid chromatography (D-HPLC) and sequencing, we screened for ABL
      mutations in a total of 178 bone marrow and/or peripheral blood samples from 40
      late chronic phase CML patients homogeneously treated with imatinib 400 mg/d, who
      did not reach a major cytogenetic response at 12 months. RESULTS: Mutations were
      found in 19 of 40 patients (48%). Mutations were already detectable by D-HPLC at
      a median of 3 months from the onset of therapy. The presence of a missense
      mutation was significantly associated with a greater likelihood of subsequent
      progression to accelerated phase/blast crisis (P = .0002) and shorter survival (P
      = .001). Patients carrying mutations falling within the P-loop seemed to have a
      particularly poor outcome in terms of time to progression (P = .032) and survival
      (P = .045). CONCLUSION: Our results show that, irrespective of the hematologic
      response, monitoring for emerging mutations in the first months of therapy may
      play a role in detecting patients with worse prognosis, for whom a revision of
      the therapeutic strategy should be considered.

PMID- 15867199
TI  - Evidence for distinct pathomechanisms in genetic subgroups of chronic lymphocytic
      leukemia revealed by quantitative expression analysis of cell cycle, activation,
      and apoptosis-associated genes.
AB  - PURPOSE: In patients with chronic lymphocytic leukemia (CLL), the VH mutation
      status and genomic aberrations (13q-, +12q, 11q-, 17p-) identify distinct
      prognostic subgroups. The aim was to elucidate biologic mechanisms through which
      these genetic markers may exert their pathogenic influence. PATIENTS AND METHODS:
      Twenty-four genes involved in apoptosis, cell cycle, B-cell activation, and B
      cell receptor (BCR) signaling were analyzed by real-time quantitative reverse
      transcription polymerase chain reaction (RQ-PCR) in 82 CLL cases constituting
      prototypic genetic CLL subgroups as defined by the VH mutation status and the
      genomic aberrations 13q-, +12, 11q-, and 17p-. RESULTS: The VH mutation subgroups
      were characterized by a differential expression of the BCR associated genes ZAP70
      and PI3K. Among the subgroups defined by genomic aberrations, there was a
      deregulation of candidate genes from the affected critical genomic regions such
      as CDK4 (up), ATM (down), and TP53 (down) in the groups +12, 11q-, and 17p-,
      respectively. Additionally, the genomic subgroups were characterized by a
      significant deregulation of cell cycle and apoptosis regulators: AKT (up) in 13q,
      E2F1 (up) in +12, MYC (up) and BCL-2 (down) in 17p-, and CCND3 (down) in 11q- as
      well as 17p-. The 17p- subgroup showed an additional down-regulation of BCR
      associated genes such as SYK and PI3K. CONCLUSION: The characteristic gene
      expression patterns observed implicate a differential regulation of cell cycle,
      apoptosis, and BCR signaling in the genetic subgroups illustrating distinct
      pathomechanisms and are evidence for a gene dosage effect being operative in CLL.
      These findings link the biologic diversity and clinical heterogeneity of CLL.

PMID- 15867200
TI  - Combined analysis of efficacy: the addition of bevacizumab to
      fluorouracil/leucovorin improves survival for patients with metastatic colorectal
      cancer.
AB  - PURPOSE: Bevacizumab (Avastin; Genentech Inc, South San Francisco, CA), a
      recombinant, humanized anti-vascular endothelial growth factor monoclonal
      antibody that inhibits tumor angiogenesis, has demonstrated survival benefit in
      patients with previously untreated metastatic colorectal cancer when combined
      with irinotecan/fluorouracil (FU)/leucovorin (LV; IFL). Three randomized clinical
      studies have evaluated bevacizumab in combination with FU/LV alone. A combined
      analysis of raw data from these studies was performed to better assess the
      efficacy of bevacizumab with FU/LV. PATIENTS AND METHODS: The analysis used
      primary efficacy data from three independent studies, including 241 patients in a
      combined control group receiving either FU/LV or IFL and 249 patients receiving
      FU/LV/bevacizumab (5 mg/kg once every 2 weeks). The efficacy data included
      response rate, progression-free survival, and overall survival. RESULTS: The
      median duration of survival was 17.9 months in the FU/LV/bevacizumab group,
      compared with 14.6 months in the combined control group, corresponding to a
      hazard ratio for death of 0.74 (P = .008). The median duration of progression
      free survival was 8.8 months in the FU/LV/bevacizumab group, compared with 5.6
      months in the combined control group, corresponding to a hazard ratio for disease
      progression of 0.63 (P < or = .0001). The addition of bevacizumab also improved
      the response rate (34.1% v 24.5%; P = .019). CONCLUSION: The addition of
      bevacizumab to FU/LV provides a statistically significant and clinically relevant
      benefit to patients with previously untreated metastatic colorectal cancer.

PMID- 15867201
TI  - The theoretical basis of transcriptional therapy of cancer: can it be put into
      practice?
AB  - Aberrant gene silencing is a frequent event in cancer and plays a critical role
      in the molecular pathogenesis of malignant transformation. The two major
      mechanisms of silencing in cancer include transcriptional repression by mutated
      or aberrantly expressed transcription factors, and aberrant epigenetic silencing
      by hypermethylation of tumor suppressor or DNA repair-related genes. Both of
      these mechanisms require the activities of multiprotein chromatin remodeling and
      modifying machines, several of which may be mutated in cancer. The end result is
      genetic reprogramming of cells to express combinations of genes that confer the
      neoplastic phenotype. Recent discoveries in transcriptional biochemistry and gene
      regulation indicate that therapeutic agents can be engineered to specifically
      target these mechanisms. We provide a framework for the clinical or translational
      scientist to consider how such drugs might be developed and what their impact
      might be on restoring cells to normal genetic programming.

PMID- 15867202
TI  - Phase II study of G3139, a Bcl-2 antisense oligonucleotide, in combination with
      dexamethasone and thalidomide in relapsed multiple myeloma patients.
AB  - PURPOSE: Bcl-2 regulates the mitochondrial apoptosis pathway that promotes
      chemotherapy resistance. Bcl-2 antisense oligonucleotide, G3139, targets Bcl-2
      mRNA. PATIENTS AND METHODS: G3139 was administered (3 to 7 mg/kg/d for 7 days) by
      continuous intravenous infusion. On day 4, patients started thalidomide (100 to
      400 mg as tolerated) and dexamethasone (40 mg daily for 4 days) on 21-day cycles
      for three cycles. Stable and responding patients continued on 35-day cycles for 2
      years. RESULTS: Thirty-three patients (median age, 60 years; range, 28 to 76
      years) received 220 cycles. Patients received a median of three prior regimens
      including thalidomide (n = 15) and stem-cell transplantation (n = 31). The
      regimen was well tolerated; the median number of cycles per patient was eight
      (range, one to 16+ cycles). Toxicities included reversible increase in
      creatinine, thrombocytopenia, neutropenia, fatigue, anorexia, constipation,
      fever, neuropathy, edema, electrolyte disturbances, and hyperglycemia. Fifty-five
      percent of patients had objective responses, including two complete responses
      (CRs), four near CRs (positive immunofixation), and 12 partial responses; six
      patients had minimal responses (MRs). Of patients who received prior thalidomide,
      seven had objective responses, and three had MRs. The median duration of response
      was 13 months, and estimated progression-free and overall survival times were 12
      and 17.4 months, respectively. Responding patients had significant increase in
      polyclonal immunoglobulin M (P = .005), indicating innate immune system
      activation. Western blot analysis of Bcl-2 protein isolated from myeloma cells
      before and after G3139 demonstrated a decrease of Bcl-2 levels in three of seven
      patients compared with six of nine patients using reverse transcriptase
      polymerase chain reaction. CONCLUSION: G3139, dexamethasone, and thalidomide are
      well tolerated and result in encouraging clinical responses in relapsed multiple
      myeloma patients.

PMID- 15867203
TI  - Inactivation of the lamin A/C gene by CpG island promoter hypermethylation in
      hematologic malignancies, and its association with poor survival in nodal diffuse
      large B-cell lymphoma.
AB  - PURPOSE: Lamins support the nuclear envelope and provide anchorage sites for
      chromatin, but they are also involved in DNA synthesis, transcription, and
      apoptosis. Although the lack of expression of A-type lamins in lymphoma and
      leukemia has been reported, the mechanism was unknown. We investigated the
      possible role of CpG island hypermethylation in lamin A/C silencing and its
      prognostic relevance. PATIENTS AND METHODS: The promoter CpG island methylation
      status of the lamin A/C gene, encoding the A-type lamins, was analyzed by
      bisulfite genomic sequencing and methylation-specific polymerase chain reaction
      in human cancer cell lines (n = 74; from 17 tumor types), and primary leukemias
      (n = 60) and lymphomas (n = 80). Lamin A/C expression was determined by reverse
      transcription polymerase chain reaction, Western blot, immunohistochemistry, and
      immunofluorescence. RESULTS: seven (50%) of 14 leukemia- and five (42%) of 13
      lymphoma cell lines. The presence of hypermethylation was associated with the
      loss of gene expression while a demethylating agent restored expression. In
      primary malignancies, lamin A/C hypermethylation was present in 18% (nine of 50)
      of acute lymphoblastic leukemias and 34% (14 of 41) of nodal diffuse large B-cell
      lymphomas. The presence of lamin A/C hypermethylation in nodal diffuse large B
      cell lymphomas correlated strongly with a decrease in failure-free survival
      (Kaplan-Meier, P = .0001) and overall survival (Kaplan-Meier, P = .0005).
      CONCLUSION: Epigenetic silencing of the lamin A/C gene by CpG island promoter
      hypermethylation is responsible for the loss of expression of A-type lamins in
      leukemias and lymphomas. The finding that lamin A/C hypermethylation is
      associated with poor outcome in diffuse large B-cell lymphomas suggests important
      clinical implications.

PMID- 15867204
TI  - Long-term results of the R-CHOP study in the treatment of elderly patients with
      diffuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de
      l'Adulte.
AB  - PURPOSE: To analyze the long-term outcome of patients included in the Lymphome
      Non Hodgkinien study 98-5 (LNH98-5) comparing cyclophosphamide, doxorubicin,
      vincristine, and prednisone (CHOP) to rituximab plus CHOP (R-CHOP) in elderly
      patients with diffuse large B-cell lymphoma. PATIENTS AND METHODS: LNH98-5 was a
      randomized study that included 399 previously untreated patients, age 60 to 80
      years, with diffuse large B-cell lymphoma. Patients received eight cycles of
      classical CHOP (cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine
      1.4 mg/m(2), and prednisone 40 mg/m(2) for 5 days) every 3 weeks. In R-CHOP,
      rituximab 375 mg/m(2) was administered the same day as CHOP. Survivals were
      analyzed using the intent-to-treat principle. RESULTS: Median follow-up is 5
      years at present. Event-free survival, progression-free survival, disease-free
      survival, and overall survival remain statistically significant in favor of the
      combination of R-CHOP (P = .00002, P < .00001, P < .00031, and P < .0073,
      respectively, in the log-rank test). Patients with low-risk or high-risk lymphoma
      according to the age-adjusted International Prognostic Index have longer
      survivals if treated with the combination. No long-term toxicity appeared to be
      associated with the R-CHOP combination. CONCLUSION: Using the combination of R
      CHOP leads to significant improvement of the outcome of elderly patients with
      diffuse large B-cell lymphoma, with significant survival benefit maintained
      during a 5-year follow-up. This combination should become the standard for
      treating these patients.

PMID- 15867205
TI  - Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics
      of PTK787/ZK 222584 administered twice daily in patients with advanced cancer.
AB  - PURPOSE: PTK787/ZK 222584 (PTK/ZK) is an oral angiogenesis inhibitor targeting
      all known vascular endothelial growth factor (VEGF) receptor tyrosine kinases,
      including VEGFR-1/Flt-1, VEGFR-2/KDR, VEGFR-3/Flt-4, the platelet-derived growth
      factor receptor tyrosine kinase, and the c-kit protein tyrosine kinase. In this
      phase I dose-escalating study, PTK/ZK was administered bid to exploit the
      theoretical advantage of maintaining constant drug levels above a threshold known
      from preclinical data to interfere with VEGF receptor signaling. PATIENTS AND
      METHODS: Forty-three patients with advanced cancers received single-agent PTK/ZK
      at doses of 150 to 1,000 mg orally bid. Assessments for safety and
      pharmacokinetics were performed. Dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) was used as a pharmacodynamic marker of response. RESULTS: At
      1,000 mg bid, the dose-limiting toxicity of reversible grade 3 lightheadedness
      was observed. Dose-related grade 3 fatigue and vomiting were observed but these
      were not dose-limiting. Pharmacokinetic data confirmed that PTK/ZK exposure
      increased with increasing dose up to 500 mg bid and appeared to plateau at higher
      doses. A greater than 40% reduction in the DCE-MRI bidirectional transfer
      constant (K(i)) at day 2 predicted for nonprogression of disease. CONCLUSION: The
      maximum-tolerated oral dose of PTK/ZK is 750 mg orally bid. DCE-MRI and
      pharmacokinetic data indicate that PTK/ZK >/= 1,000 mg total daily dose is the
      biologically active dose.

PMID- 15867206
TI  - Transforming growth factor-beta, Smads, and cancer.

PMID- 15867207
TI  - Cell death independent of caspases: a review.
AB  - Patterns of cell death have been divided into apoptosis, which is actively
      executed by specific proteases, the caspases, and accidental necrosis. However,
      there is now accumulating evidence indicating that cell death can occur in a
      programmed fashion but in complete absence and independent of caspase activation.
      Alternative models of programmed cell death (PCD) have therefore been proposed,
      including autophagy, paraptosis, mitotic catastrophe, and the descriptive model
      of apoptosis-like and necrosis-like PCD. Caspase-independent cell death pathways
      are important safeguard mechanisms to protect the organism against unwanted and
      potential harmful cells when caspase-mediated routes fail but can also be
      triggered in response to cytotoxic agents or other death stimuli. As in
      apoptosis, the mitochondrion can play a key role but also other organelles such
      as lysosomes and the endoplasmic reticulum have an important function in the
      release and activation of death factors such as cathepsins, calpains, and other
      proteases. Here we review the various models of PCD and their death pathways at
      molecular and organelle level and discuss the relevance of the growing knowledge
      of caspase-independent cell death pathways for cancer.

PMID- 15867208
TI  - Mining the tumor phosphoproteome for cancer markers.
AB  - Despite decades of cancer research, mortality rates remain high largely due to
      the failure of early detection, poor understanding of the epidemiology of
      rational drug targets, and molecular etiology of human cancers. The discovery of
      disease markers promises to deliver some solutions to these formidable
      challenges. Gene and protein expression profiling through DNA microarray and
      proteomics have already made a tremendous effect in this area. However,
      protein/gene expression does not necessarily reflect protein activity, which is
      often regulated via post-translation modifications, of which phosphorylation is
      one of the most prominent. This is an important consideration because the
      activity of protein is a more relevant phenotype than its expression during
      pathogenesis. Tyrosine kinases represent a very important class of enzymes that
      are critical regulators of mitogenic and angiogenic signaling, hence attractive
      targets for anticancer drugs as exemplified by BCR-ABL and ErbB2. More than 50%
      of them are overexpressed or mutated resulting in a gain of function in various
      human cancers. In this review, we discuss the potential effect of phosphoproteins
      as cancer markers in cancer diagnosis and therapeutics. Phosphoproteomics
      strategies that might pave the way to high-throughput analysis for routine
      clinical applications are also described.

PMID- 15867209
TI  - Increased estrogen receptor betacx expression during mammary carcinogenesis.
AB  - Identification of proteins that markedly vary during early steps of mammary
      carcinogenesis may help to understand its pathophysiology and to develop a
      prevention strategy. The expression of total estrogen receptor beta (ERbeta)
      protein and of its COOH-terminally spliced variant ERbetacx (or ERbeta2) was
      compared in 43 invasive breast cancers and in 39 adjacent normal mammary glands
      and 26 ductal carcinoma in situ (DCIS). Thirty-six breast cancers were ER
      positive by radioligand binding assay. The analysis was done by
      immunohistochemistry on adjacent sections of formalin-fixed, paraffin-embedded
      tumors using polyclonal anti-ERbeta 503 IgY and sheep polyclonal ERbetacx
      antibodies that were previously validated. Nuclear staining was quantified using
      a computerized image analyzer in selected areas of normal and cancer epithelial
      cells. Total ERbeta expression was high in normal glands, decreased in DCIS (P =
      0.0004), and increased from DCIS to invasive tumors (P = 0.029). In contrast, the
      ERbetacx expression was low in normal glands, increased significantly in DCIS (P
      = 0.0014), and continued to increase in invasive carcinomas (P = 0.0027) in both
      ERalpha-positive and ERalpha-negative tumors. This is the first study showing a
      significant increase of the ERbetacx variant protein in DCIS and invasive breast
      cancer compared with adjacent normal glands. This contrasts with the decrease of
      the total ERbeta level in the same patients and indicates different mechanisms to
      explain these variations during mammary carcinogenesis. It also suggests a role
      of the ERbetacx variant in carcinogenesis opposite to the protective effect of
      the wild-type ERbeta1.

PMID- 15867210
TI  - Ferritin contributes to melanoma progression by modulating cell growth and
      sensitivity to oxidative stress.
AB  - PURPOSE: Employing an in vitro model system of human melanoma progression, we
      previously reported ferritin light chain (L-ferritin) gene overexpression in the
      metastatic phenotype. Here, we attempted to characterize the role of ferritin in
      the biology of human melanoma and in the progression of this disease.
      EXPERIMENTAL DESIGN: Starting from the LM human metastatic melanoma cell line, we
      engineered cell clones in which L-ferritin gene expression was down-regulated by
      the stable expression of a specific antisense construct. These cells were then
      assayed for their growth capabilities, chemoinvasive properties, and sensitivity
      to oxidative stress. Additionally, ferritin protein content in primary and
      metastatic human melanomas was determined by immunohistochemistry. RESULTS:
      Artificial L-ferritin down-regulation in the LM cells strongly inhibited
      proliferation and chemoinvasion in vitro and cell growth in vivo. In addition, L
      ferritin down-regulated cells displayed enhanced sensitivity to oxidative stress
      and to apoptosis. Concurrently, immunohistochemical analysis of a human melanoma
      tissue array revealed that ferritin expression level in metastatic lesions was
      significantly higher (P < 0.0001) than in primary melanomas. Furthermore,
      ferritin expression was constantly up-regulated in autologous lymph node melanoma
      metastases when compared with the respective primary tumors in a cohort of 11
      patients. CONCLUSIONS: These data suggest that high ferritin expression can
      enhance cell growth and improve resistance to oxidative stress in metastatic
      melanoma cells by interfering with their cellular antioxidant system. The
      potential significance of these findings deserves to be validated in a clinical
      setting.

PMID- 15867211
TI  - Down-regulation and growth inhibitory role of C/EBPalpha in breast cancer.
AB  - PURPOSE: CCAAT/enhancer binding proteins (C/EBP) are a family of transcription
      factors that regulate proliferation and differentiation in a variety of tissues.
      The purpose of this study was to explore the possibility that C/EBPalpha is
      involved in breast cancer. EXPERIMENTAL DESIGN: We quantified C/EBPalpha mRNA
      expression levels in 24 primary breast tumors, 16 normal breast samples, and 8
      breast cancer cell lines using quantitative real-time reverse transcription-PCR
      assay. C/EBPalpha protein levels were further determined by immunohistochemical
      analysis. To examine the consequence of C/EPBalpha expression in breast cancer,
      we stably transfected an inducible C/EPBalpha expression vector into three breast
      cancer cell lines. RESULTS: Low expression of C/EBPalpha mRNA was found in 83% of
      primary breast cancer samples. Immunohistochemical study further showed either a
      markedly reduced or undetectable expression of C/EBPalpha protein in 30% of
      breast cancer specimens. The other 70% of breast cancers had C/EBPalpha
      expression in both the cytoplasm and nucleus; in control, C/EBPalpha was
      localized to the nucleus in the normal ductal cells. C/EBPalpha expression was
      associated with estrogen- and progesterone receptor-negative status. Induction of
      C/EBPalpha expression in these cell lines resulted in growth inhibition
      accompanied by G0-G1 cell cycle arrest and reduced anchorage-independent cell
      growth. C/EBPalpha expression was associated with down-regulation of c-myc and up
      regulation of p21, PPARgamma, and the breast epithelial differentiation marker,
      maspin. CONCLUSIONS: These results suggest that reduced expression of C/EBPalpha
      may play a role in the development and/or progression of breast cancer.

PMID- 15867212
TI  - Differences in Smad4 expression in human papillomavirus type 16-positive and
      human papillomavirus type 16-negative head and neck squamous cell carcinoma.
AB  - The SMADs are a group of interrelated proteins that mediate transforming growth
      factor beta (TGF-beta) signaling. Upon TGF-beta binding the TGF-beta type I
      receptor phosphorylates Smad2 and Smad3, which then complex with Smad4 and
      translocate to the nucleus, with subsequent activation of target genes.
      Disruption of TGF-beta signaling is thought to contribute to the development of
      head and neck squamous cell carcinomas (HNSCC). Alterations in the function of
      the DPC4/Smad4 tumor suppressor gene have been found to inactivate TGF-beta
      signaling in several tumor types. For example, DPC4/Smad4 is lost or mutated in
      colorectal, pancreatic, and esophageal cancers. In addition, DPC4/Smad4
      transcriptional activity and TGF-beta ability to inhibit DNA synthesis is blocked
      by the E7 protein of the human papillomavirus type 16 (HPV16) in cervical
      carcinoma cell lines. HPV16 infection is a risk factor for the development of a
      subset of HNSCC. This study was undertaken to investigate a potential correlation
      between expression of components of the TGF-beta signaling pathway and HPV16
      status in HNSCC tumors. We examined the expression of TGF-beta signaling proteins
      Smad2, Smad2-P, and Smad4 by immunohistochemistry in 27 HPV16-negative and 16
      HPV16-positive HNSCCs. We compared the expression patterns and assessed their
      relationship to HPV16 status. No significant differences were detected between
      HPV16-positive and HPV16-negative tumors in the expression of Smad2 and Smad2-P.
      Smad4 expression, however, was decreased in 56% of the HPV16-positive tumors and
      in 39% of HPV16-negative tumors. This difference was statistically significant (P
      = 0.01) suggesting that loss of Smad4 expression may be involved in HPV16-induced
      carcinogenesis of HNSCC.

PMID- 15867213
TI  - Int6 expression can predict survival in early-stage non-small cell lung cancer
      patients.
AB  - PURPOSE: The Int6 gene was originally identified as a common insertion site for
      the mouse mammary tumor virus in virally induced mouse mammary tumors. Recent
      studies indicate that Int6 is a multifaceted protein involved in the regulation
      of protein translation and degradation through binding with three complexes: the
      eukaryotic translation initiation factor 3, the proteasome regulatory lid, and
      the constitutive photomorphogenesis 9 signalosome. This study aimed to
      investigate the prognostic role of Int6 in a large series of stage I non-small
      cell lung cancers (NSCLC) patients with long-term follow-up. EXPERIMENTAL DESIGN:
      We determined the methylation status of Int6 DNA by methylation-specific PCR and
      the steady-state levels of Int6 RNA by quantitative real-time reverse
      transcription-PCR in 101 NSCLCs and matched normal lung tissues. RESULTS: In 27%
      of the tumors, Int6 RNA levels were reduced relative to normal tissue. In 85% of
      the tumors with reduced Int6 expression, the transcription promoter and first
      exon were hypermethylated, whereas only 4% of the tumors with elevated Int6 RNA
      levels were hypermethylated (P <0.000001). Low levels of Int6 RNA were found a
      significant predictor of overall and disease-free survival (P=0.0004 and
      P=0.0020, respectively). A multivariate analysis confirmed that low Int6
      expression was the only independent factor to predict poor prognosis, for both
      overall (P=0.0006) and disease-free (P=0.024) survival. CONCLUSIONS: Our results
      suggest that Int6 expression, evaluated by quantitative real-time PCR, may
      represent a new prognostic factor in patients with stage I NSCLC.

PMID- 15867214
TI  - Serum human telomerase reverse transcriptase messenger RNA as a novel tumor
      marker for hepatocellular carcinoma.
AB  - PURPOSE: We previously reported the usefulness of a qualified highly sensitive
      detection method for human telomerase reverse transcriptase (hTERT) mRNA in serum
      with 89.7% sensitivity for hepatocellular carcinoma (HCC). In this study, we
      developed a quantitative detection method for serum hTERT mRNA and examined the
      clinical significance in HCC diagnosis. EXPERIMENTAL BACKGROUND: In 64 patients
      with HCC, 20 with liver cirrhosis, 20 with chronic hepatitis, and 50 healthy
      individuals, we measured serum hTERT mRNA by using the newly developed real-time
      quantitative reverse transcription-PCR with SYBR Green I. We examined its
      sensitivity and specificity in HCC diagnosis, clinical significance in comparison
      with other tumor markers, and its correlations with the clinical variables by
      using multivariate analyses. RESULTS: Serum hTERT mRNA showed higher values in
      patients with HCC than those with chronic liver diseases. hTERT mRNA expression
      was shown to be independently correlated with clinical variables such as tumor
      size, number, and degree of differentiation (P < 0.001, each). The
      sensitivity/specificity of hTERT mRNA and alpha-fetoprotein (AFP) mRNA in HCC
      diagnosis were 88.2%/70.0% for hTERT and 71.6%/67.5% for AFP, respectively. hTERT
      mRNA proved to be superior to AFP mRNA, AFP, and des-gamma-carboxy prothrombin in
      HCC diagnosis. Furthermore, hTERT mRNA in serum was associated with that in HCC
      tissue. CONCLUSIONS: The usefulness of hTERT mRNA expression in HCC diagnosis and
      its superiority to conventional tumor markers were shown. Therefore, serum hTERT
      mRNA is a novel and available marker for HCC diagnosis.

PMID- 15867215
TI  - Fluorodeoxyglucose positron emission tomography as an outcome measure for
      castrate metastatic prostate cancer treated with antimicrotubule chemotherapy.
AB  - PURPOSE: Standard imaging studies are limited as outcome measures for patients
      with metastatic prostate cancer. We tested the hypothesis that serial
      fluorodeoxyglucose positron emission tomography (FDG-PET) scans can serve as an
      outcome measure for patients with castrate metastatic prostate cancer treated
      with antimicrotubule chemotherapy. EXPERIMENTAL DESIGN: FDG-PET scans were done
      at baseline, 4, and 12 weeks of treatment. The average maximum standardized
      uptake value (SUVmaxavg) was measured in up to five lesions and was tested as the
      quantitative outcome measure. Prostate-specific antigen (PSA) at 4 weeks and PSA,
      bone scan, and soft tissue imaging at 12 weeks were considered standard outcome
      measures. The change in SUVmaxavg that distinguished clinically assessed
      progression from nonprogression was sought. RESULTS: Twenty-two PET scans were
      reviewed and compared with PSA at 4 weeks; 18 PETs were compared at 12 weeks with
      standard outcome measures. Applying the PSA Working Group Consensus Criteria
      guideline that a 25% PSA increase constitutes progression to the SUVmaxavg, PET
      correctly identified the clinical status of 20 of 22 patients (91%) at 4 weeks
      and 17 of 18 patients at 12 weeks (94%). The accuracy of PET could be further
      optimized if a >33% increase in PSA and SUVmaxavg were used to define
      progression. CONCLUSION: FDG-PET is promising as an outcome measure in prostate
      cancer. As a single modality, it can show treatment effects that are usually
      described by a combination of PSA, bone scintigraphy, and soft tissue imaging.
      Preliminarily, a >33% increase in SUVmaxavg or the appearance of a new lesion
      optimally dichotomizes patients as progressors or nonprogressors.

PMID- 15867216
TI  - Activation of the RAS pathway is predictive for a chemosensitive phenotype of
      acute myelogenous leukemia blasts.
AB  - PURPOSE: Activation of the RAS pathway plays a major role in cancer cells. In
      acute myeloid leukemia (AML), mutations of the RAS genes cause an intrinsic
      activation of this pathway. Until now, clinical studies could not find clear
      association of RAS mutations with the clinical outcome after AML therapy. This
      could be due to alternative initiating events for activation of the RAS pathway
      like constitutive tyrosine kinase activation or mutations in Ras-regulating
      genes. EXPERIMENTAL DESIGN: In total, 191 AML patients (126 as training
      population and 65 as test population) were studied for Ras activity with a
      glutathione S-transferase pull-down assay using Raf binding of activated Ras.
      RESULTS: AML samples showed a wide range of Ras activity values, which was in
      contrast to normal bone marrow donors who showed no or very limited Ras activity.
      Using a Ras binding score based on semiquantitative Western blotting, we defined
      patients with strong Ras activity and compared Ras activity with RAS mutation.
      Surprisingly, only a minority of RAS mutated AML samples (22.2%) showed strong
      Ras activity, whereas 25 patients presented strong Ras activity in the absence of
      RAS mutations. Clinical outcome did not show differences according to RAS
      mutations. In contrast, Ras activity predicted for a high response rate (P <0.05)
      and proved to be an independent factor for overall survival rate (P <0.05) in
      younger AML patients receiving high-dose 1-beta-D-arabinofuranosylcytosine as
      induction therapy. CONCLUSION: The data highlight the role for alternative
      pathways of Ras activation without RAS mutations. Intrinsically activated Ras
      seems to increase sensitivity of the AML blast to high-dose 1-beta-D
      arabinofuranosylcytosine therapy.

PMID- 15867217
TI  - Vascular endothelial growth factor-C expression and invasive phenotype in ovarian
      carcinomas.
AB  - PURPOSE: To investigate the biological correlation between vascular endothelial
      growth factor (VEGF)-C expression and invasive phenotype in ovarian carcinomas.
      EXPERIMENTAL DESIGN: Gene and protein expression levels of VEGF-C in 10 ovarian
      carcinoma cell lines were correlated with invasive activity of the cells. The
      correlation between immunohistochemical expression of VEGF-C and tumor
      aggressiveness in 73 ovarian carcinomas was also examined with respect to
      clinicopathologic features and patient outcome. RESULTS: VEGF-C gene and protein
      expression differed remarkably among the cell lines, and there was a statistical
      correlation among VEGF-C expression, in vitro invasive activity, and matrix
      metalloproteinase-2 (MMP-2) gene expression and its activity. Anti-VEGF-C and
      anti-MMP-2 antibodies inhibited the invasive activity of tumor cells. VEGF-C
      expression in clinical tissue samples was well correlated with clinical stages,
      retroperitoneal lymph node metastasis, MMP-2 expression, angiogenesis,
      lymphangiogenesis, and low apoptotic index (AI). The patients whose tumors had
      strong VEGF-C expression and low AI underwent a poorer prognosis than did those
      with weak VEGF-C expression and high AI. CONCLUSION: VEGF-C expression is closely
      related to invasive phenotype and affects the patient's survival in ovarian
      carcinomas.

PMID- 15867218
TI  - Increased expression of insulin-like growth factor I and/or its receptor in
      gastrinomas is associated with low curability, increased growth, and development
      of metastases.
AB  - PURPOSE: Growth factors, particularly insulin-like growth factor I (IGF-I) and
      IGF-I receptor (IGF-IR) in some nonendocrine and a few endocrine tumors, are
      thought important in recurrence, growth, and aggressiveness. Whether this is true
      of neuroendocrine tumors such as gastrinomas is unclear. The aim of this study
      was to address this question in gastrinomas. EXPERIMENTAL DESIGN: IGF-I and IGF
      IR expression in gastrinomas from 54 patients with Zollinger-Ellison syndrome
      were analyzed and correlated with clinical/tumor characteristics. IGF-I and IGF
      IR mRNA levels were determined by competitive reverse transcription-PCR. IGF-IR
      expression, assessed by immunohistochemistry, was done on a subset. RESULTS: IGF
      IR mRNA was found in 100% and IGF-I in 89%. IGF-I mRNA expression varied by >254
      fold, IGF-IR by 2,670-fold, and the levels correlated in a given tumor. The IGF
      IR level was lower in gastrinomas of patients who were rendered disease free and
      increased levels correlated with tumor growth, aggressiveness, extent, and with
      liver metastases. Increased IGF-I levels correlated with increased growth, tumor
      extent, and aggressiveness. Neither IGF-IR nor IGF-I levels correlated with tumor
      location, size, or its clinical/functional features. The IGF-IR correlated with
      disease-free survival. IGF-IRbeta was found in 31 of 32 tumors (97%) by
      immunohistochemistry. CONCLUSIONS: These results indicate that IGF-I and IGF-IR
      are expressed in almost all gastrinomas. Furthermore, assessment of IGF-I/IGF-IR
      expression in gastrinomas may be clinically useful in identifying those patients
      with more aggressive tumors who might benefit from more aggressive treatment.

PMID- 15867219
TI  - Noninvasive detection of prostate cancer by quantitative analysis of telomerase
      activity.
AB  - PURPOSE: Prostate cancer is the most common male malignancy and the second
      leading cause of male cancer death; therefore, there is urgent necessity for
      noninvasive assays for early detection of prostate cancer. Obtaining prostate
      tumor samples surgically is problematic because the malignancy is heterogeneous
      and multifocal and early-stage tumors are nonpalpable. In contrast, exfoliated
      cells represent the cancer status of the entire gland better due to the general
      tendency of cancer cells to exfoliate into biological fluids. The purpose of this
      study was to clarify whether quantitative analysis of telomerase activity in
      exfoliated cells in urine could serve as a reliable molecular marker of prostate
      malignancy. EXPERIMENTAL DESIGN: We analyzed prospectively post-prostatic
      examination-exfoliated cells from the urine of 56 patients undergoing routine
      prostate screening. Epithelial cells were isolated and enriched by immunomagnetic
      separation. Telomerase activity was analyzed by quantitative real-time PCR
      telomeric-repeat amplification protocol assay using Opticon MJ research
      instrument. RESULTS: We report now that all prostate cancer patients revealed
      high levels of telomerase activity thereby showing 100% of the assay sensitivity.
      In contrast, the majority of patients with clinically confirmed benign prostatic
      hyperplasia (BPH) did not express any telomerase activity (70% of all BPH
      patients), most likely presenting cancer-free cases, or expressed low levels of
      activity (18%). However, about 12% of BPH patients revealed high levels of
      telomerase activity that potentially can reflect hidden prostate cancer.
      CONCLUSIONS: We suggest that the quantitative analysis of telomerase activity can
      be useful for the selection of prostate cancer and cancer-free cases.

PMID- 15867220
TI  - Cyclooxygenase-2 expression correlates with local chronic inflammation and tumor
      neovascularization in human prostate cancer.
AB  - PURPOSE: Chronic inflammation is linked to the development of cancer in several
      organs, including the prostate. Up-regulated cyclooxygenase-2 (COX-2) may play a
      role in influencing cell proliferation, differentiation, apoptosis, or
      angiogenesis. This study aimed to derive data from human prostate cancer to
      investigate whether chronic inflammation and angiogenesis were correlated with
      the expression of COX-2. EXPERIMENTAL DESIGN: In this study, we did double
      immunohistochemical analysis of a set of 43 human prostate cancer for COX-2
      expression and the correlation with T-lymphocyte and macrophage densities and
      CD31-marked microvessel density (MVD) in situ. RESULTS: COX-2 positive staining
      was detected in 40/43 cancer samples with the very heterogeneous expression.
      Elevated COX-2 expression was associated with high Gleason score (P = 0.002).
      Foci of chronic inflammation were found in all 43 samples. COX-2-positive areas
      were noted with high T-lymphocyte and macrophage densities than COX-2-negative
      tumor areas (P < 0.0001 and P = 0.001, respectively). MVD were also found higher
      in COX-2-positive areas than in COX-2-negative tumor areas (P = 0.001).
      CONCLUSIONS: This study shows a novel relationship between COX-2 expression and
      the local chronic inflammation within prostate cancer and the increased
      angiogenesis. It is likely that the proinflammatory cytokines, released by T
      lymphocytes and macrophages, up-regulate COX-2 in adjacent tumor cells and
      stimulate the angiogenesis in stromal tissues. These findings suggest that COX-2
      may be an effective therapeutic target in prostate cancer treatment.

PMID- 15867221
TI  - Tissue inhibitor of matrix metalloproteinase-1 is prognostic in head and neck
      squamous cell carcinoma: comparison of the circulating and tissue immunoreactive
      protein.
AB  - PURPOSE: Tissue inhibitors of metalloproteinases (TIMP) are capable of inhibiting
      the matrix metalloproteinases, but they also possess other biological functions.
      Little is known about the role of TIMP-1 in the progression and spreading of
      cancer cells among patients with head and neck squamous cell carcinoma (HNSCC).
      In this study, the pretreatment serum levels of TIMP-1 or the overexpression of
      TIMP-1 immunoreactive protein in the primary tumor was correlated to the clinical
      course in patients with HNSCC. EXPERIMENTAL DESIGN: The TIMP-1 immunoreactive
      protein was studied in 74 cases representing HNSCC. The tissue immunoreactive
      protein was evaluated from paraffin-embedded tumor sections in 68 cases using
      immunohistologic staining with a specific antibody, and in 68 cases the
      pretreatment serum levels of TIMP-1 were quantitatively measured by ELISA assay.
      The results were compared with the clinicopathologic factors of the disease and
      the patients' outcome. RESULTS: A positive correlation was found between the size
      of the primary tumor (T) and the circulating TIMP-1 level (P = 0.021) or the
      positive immunoreaction of TIMP-1 in tumor (P = 0.039). The 5-year cause-specific
      survival was significantly lower in patients presenting with a high serum TIMP-1
      level than in those with a low level of TIMP-1 (38% versus 64%, P = 0.034). They
      also had an unfavorable 5-year relapse-free survival rate (37% versus 56%,
      respectively). Similarly, the expression of TIMP-1 in tumor was prognostic for
      shortened survival, the 5-year cumulative relapse-free survival being 42% in
      patients with a TIMP-1-positive tumor versus 75% in cases with a negative tumor
      (P = 0.035). Tissue TIMP-1 positivity also seemed associated to the cause
      specific survival (P = 0.075) and to be connected with later lymph node or
      hematogenic relapses. CONCLUSIONS: This study shows for the first time that both
      circulating and tissue TIMP-1 immunoreactive protein predicts the clinical course
      and dissemination in HNSCC, suggesting that TIMP-1 might be related to both tumor
      growth and metastasis in HNSCC.

PMID- 15867222
TI  - Expression of cell cycle-regulated proteins pRB2/p130, p107, E2F4, p27, and pCNA
      in salivary gland tumors: prognostic and diagnostic implications.
AB  - The retinoblastoma family consists of the tumor suppressor nuclear phosphoprotein
      pRb/p105 and related proteins p107 and pRb2/p130. Recent immunohistochemical
      studies of the retinoblastoma family of proteins in lung and endometrial cancer
      and choroidal melanomas show a tight inverse correlation between the histologic
      grading in the most aggressive tumor types and pRb2/p130 expression. This led us
      to investigate the role of pRb2/p130 in salivary tumors. We studied the
      expression of pRb2/p130, p107, E2F4, p27, and PcNA by immunohistochemistry in a
      panel of 44 salivary gland tumors. We found a direct correlation between the
      cytoplasmic expression of pRb2/p130 and tumor grading and the presence of
      metastasis that was highly statistically significant (P < 0.001). Additionally,
      increased cytoplasmic pRb2/p130 expression was significantly correlated with a
      decreased probability of survival (P < 0.001). Interestingly, p107 nuclear
      expression showed a strong direct correlation when compared with the same
      variables. pRb2/p130 showed the highest percentage of undetectable nuclear levels
      in the specimens examined and the tightest inverse correlation (P < 0.0001) with
      both the histologic grading and pCNA expression in malignant salivary tumors.
      Additionally, E2F4 showed an identical localization pattern as to that of
      pRb2/p130. These data suggests an important role for pRb2/p130 in the
      pathogenesis and progression of certain salivary gland cancers.

PMID- 15867223
TI  - 14-3-3sigma expression is an independent prognostic parameter for poor survival
      in colorectal carcinoma patients.
AB  - PURPOSE: 14-3-3sigma is an intracellular, dimeric, phosphoserine binding protein
      that is expressed in epithelial cells and involved in cancer development. In this
      study, we examined the expression of 14-3-3sigma and evaluated its clinical
      significance in colorectal carcinoma. EXPERIMENTAL DESIGN: Expression of 14-3
      3sigma was analyzed by Western blot in nine colorectal carcinoma cell lines,
      eight paired colorectal carcinoma tissues, and normal mucosas.
      Immunohistochemistry was used to evaluate expression of 14-3-3sigma in tissues of
      121 colorectal carcinoma patients and to correlate it with clinical parameters.
      RESULTS: Western blot analysis of colorectal carcinoma cell lines and tissues
      revealed strong 14-3-3sigma expression in four of eight cell lines and 14-3
      3sigma overexpression in carcinomas compared with normal mucosa in six of eight
      colorectal carcinoma tissue pairs. Immunohistochemical analysis revealed 14-3
      3sigma overexpression in 38.8% of colorectal carcinoma samples. Furthermore,
      highly positive immunoreactivity was significantly correlated with tumor
      differentiation (P < 0.001) and pT stage (P < 0.003). In Kaplan-Meier analysis,
      14-3-3sigma overexpression was associated with a significantly decreased survival
      time compared with negatively stained or low stained cases (P < 0.0096). In
      multivariate regression analysis, 14-3-3sigma expression emerged as a significant
      independent parameter (P < 0.037). CONCLUSIONS: These results provide evidence
      that 14-3-3sigma expression increases during carcinoma progression in a subset of
      colorectal carcinoma. The overexpression of this antigen identifies patients at
      high risk. It is tempting to suggest that 14-3-3sigma overexpression either
      promotes tumor proliferation and/or prevents apoptotic signal transduction in
      colorectal carcinoma. Thus, targeting 14-3-3sigma might be a new therapeutic
      strategy in colorectal carcinoma.

PMID- 15867224
TI  - Shc family expression in neuroblastoma: high expression of shcC is associated
      with a poor prognosis in advanced neuroblastoma.
AB  - The biological features and prognosis of neuroblastoma, a neural crest-derived
      pediatric tumor, are closely associated with expression of the Trk receptor.
      Because the Shc family proteins (ShcA, ShcB, and ShcC) are adaptors for various
      receptors, including Trk receptors, and are regulators of neuronal cell
      development, we speculated that they may play a role in neuroblastoma. Therefore,
      in this study, we used semiquantitative reverse transcription-PCR to examine the
      expression of these three genes in 15 neuroblastoma cell lines, an all-trans
      retinoic acid-treated neuroblastoma cell line, and 52 tumor samples. In
      neuroblastoma cell lines and tumor samples, shcA was ubiquitously and highly
      expressed. Little expression of shcA was observed. Also, shcB was hardly
      expressed in neuroblastoma cell lines, but its expression in RT-BM-1 cells was
      enhanced after all-trans-retinoic acid-induced differentiation, and it was highly
      expressed in low-stage tumors (P = 0.0095). This suggests that ShcB participates
      in cellular differentiation and may correlate with a favorable prognosis in
      neuroblastoma. Finally, the expression of shcC was observed in most of the
      neuroblastoma cell lines and in some stage 4 patients. Patients with a high
      expression of shcC had a very poor prognosis (P < 0.0001) and amplification of
      MYCN, and all died within 31 months after diagnosis. Therefore, ShcC seems to be
      associated with an aggressive tumor phenotype, perhaps by enhancing TrkB signals.
      Our results suggest that the expressions of shcB and shcC are important
      biological factors in neuroblastoma and are useful prognostic indicators.

PMID- 15867225
TI  - Metabotropic glutamate receptor 4 expression in colorectal carcinoma and its
      prognostic significance.
AB  - PURPOSE: Metabotropic glutamate receptors (mGluR) play a variety of roles in both
      neuronal and nonneuronal cells. Recently, we reported that mGluR4 mediates 5
      fluorouracil resistance in a human colon cancer cell line. In this study, we
      evaluated the nonneural expression of mGluR4 and clarified the existence of
      mGluR4 in normal colon epithelium and colorectal carcinomas. We also investigated
      the association of mGluR4 expression levels with various clinicopathologic
      parameters. EXPERIMENTAL DESIGN: mGluR4 expression was investigated in 21 normal
      and 312 malignant tissues from various organs using immunohistochemistry. In
      addition, 241 cases of colorectal carcinomas were examined and correlations
      between mGluR4 expression and various clinicopathologic parameters were then
      statistically analyzed. RESULTS: Expression of mGluR4 was identified in the
      normal epithelia of the upper respiratory tract, gastrointestinal tracts, breast,
      uterine cervix, urinary bladder, and skin, whereas it was not detected in the
      thyroid, lung alveoli, liver, testis, or prostate. In the corresponding malignant
      tissues, mGluR4 expression was frequently identified in colorectal carcinoma
      (68%), followed by malignant melanoma, laryngeal carcinoma, and breast
      carcinomas. Expression of mGluR4 was detected in 131 (54%) of 241 colorectal
      carcinomas and 12 (5%) cases among them showed overexpression in their
      cytoplasms. Loss of mGluR4 expression was negatively associated with tumor
      differentiation (P = 0.028), whereas overexpression of mGluR4 was positively
      associated with recurrence (P = 0.034) and poor disease-free survival (P = 0.017)
      in multivariate analyses. CONCLUSIONS: Our results suggest that mGluR4 signaling
      may play a role in colorectal carcinomas and that overexpression of mGluR4 is
      associated with poor prognosis.

PMID- 15867226
TI  - Drg1 expression in 131 colorectal liver metastases: correlation with clinical
      variables and patient outcomes.
AB  - PURPOSE: The differentiation-related gene-1 (Drg1) is a recently identified gene
      down-regulated in malignancy and a putative suppressor of colorectal cancer
      metastases. Its expression is associated with improved survival in patients with
      prostate or breast cancer. Drg1 expression is also associated with resistance to
      irinotecan therapy in preclinical colorectal cancer models. The clinical
      evaluation of Drg1 in colorectal cancer has been limited. We performed this study
      to evaluate the role of Drg1 in a large cohort of patients with metastatic
      colorectal cancer who were irinotecan naive. EXPERIMENTAL DESIGN: We examined
      Drg1 expression by immunohistochemistry in 131 patients with metastatic
      colorectal cancer enrolled in a clinical trial of adjuvant fluorouracil-based
      therapy from 1991 to 1995. We correlated expression of Drg1 to numerous clinical
      and tumor related variables and to patient outcomes, including a subset of
      patients who recurred and received irinotecan-based therapy. RESULTS: Drg1
      expression was identified in all metastatic tissue samples. There was a trend for
      unilobar metastases with high Drg1 expression (P = 0.07) and a suggestion of
      improved 2-year survival (82.4% versus 69.6%, P = 0.148). High Drg1 expression
      suggested irinotecan resistance (P = 0.07). CONCLUSIONS: In colorectal cancer,
      Drg1 expression may be associated with a less aggressive, indolent colorectal
      cancer. High Drg1 may also be associated with relative resistance to irinotecan.
      The role of Drg1 in malignancy continues to be defined.

PMID- 15867227
TI  - P16 loss and mitotic activity predict poor survival in patients with peritoneal
      malignant mesothelioma.
AB  - PURPOSE: Peritoneal malignant mesothelioma is an aggressive neoplasm for which
      intensive therapy improves survival in a subset of patients. We hypothesized that
      pathologic variables would stratify patients into favorable and unfavorable
      survival subgroups. EXPERIMENTAL DESIGN: Fifty-four patients with peritoneal
      malignant mesothelioma were evaluated for trimodal therapy from 1995 to 2003. Two
      pathologists evaluated pathologic variables independently, and p16 status was
      analyzed by immunohistochemistry. RESULTS: Patients not receiving trimodal
      therapy had a significantly increased risk of death [hazard ratio (HR), 9.6; 4.3
      21.6; P < 0.0001]. Biphasic histology was also associated with increased risk of
      death (HR, 8.5; 3.4-21.8; P < 0.0001). In multivariate analysis adjusting for
      treatment modality and histologic type, high mitotic rate and p16 loss were
      associated with increased risk of death (HR, 3.074; 1.05-9.0; P < 0.04 and HR,
      3.65; 1.3-10.2; P < 0.014, respectively). CONCLUSIONS: Biphasic histology,
      increased mitotic rate, and p16 loss were independently associated with poorer
      survival in peritoneal malignant mesothelioma. Among the trimodal treated
      patients, increased mitotic rate was associated with increased risk of death.

PMID- 15867228
TI  - CD44 expression is associated with increased survival in node-negative invasive
      breast carcinoma.
AB  - PURPOSE: CD44 is a multifunctional cell surface receptor with many known splice
      variants, some of which have been reported to play a role in tumor progression.
      The purpose of this study was to evaluate the prognostic significance of CD44
      isoforms in early-stage, lymph node-negative invasive breast carcinoma.
      EXPERIMENTAL DESIGN: Immunohistochemical staining for CD44 isoforms was done on
      archival paraffin tissue sections of invasive breast carcinoma from a cohort of
      lymph node-negative patients who received no adjuvant tamoxifen or chemotherapy
      and who had a mean clinical follow-up period of 15 years. Immunohistochemical
      staining was done with antibodies to CD44s, the standard isoform of CD44, and to
      isoforms containing variant exon 6 (CD44v6); levels of staining were correlated
      with clinical outcome data. RESULTS: There was a trend towards increased disease
      free survival for patients whose tumors had high anti-CD44s positivity (P =
      0.05), and a significant association was observed between anti-CD44s positivity
      and disease-related survival (P = 0.04). Expression of CD44v6 isoforms did not
      correlate with clinical outcome. CONCLUSION: CD44 expression, as assessed by
      immunohistochemical staining with anti-CD44s, may be a favorable prognostic
      factor in patients with node-negative invasive breast carcinoma.

PMID- 15867229
TI  - Prognostic role of a multigene reverse transcriptase-PCR assay in patients with
      node-negative breast cancer not receiving adjuvant systemic therapy.
AB  - PURPOSE: To test the ability of a reverse transcriptase-PCR (RT-PCR) assay, based
      on gene expression profiles, to accurately determine the risk of recurrence in
      patients with node-negative breast cancer who did not receive systemic therapy
      using formalin-fixed, paraffin-embedded tissue. A secondary objective was to
      determine whether the quantitative RT-PCR data correlated with
      immunohistochemistry assay data regarding estrogen receptor, progesterone
      receptor, and human epidermal growth factor receptor 2 status. PATIENTS AND
      METHODS: We obtained archival paraffin-embedded tissue from patients with
      invasive breast cancer but no axillary lymph node involvement who had received no
      adjuvant systemic therapy and been followed for at least 5 years. RNA was
      extracted from three 10-microm-thick sections. The expression of 16 cancer
      related genes and 5 reference genes was quantified using RT-PCR. A gene
      expression algorithm was used to calculate a recurrence score for each patient.
      We then assessed the ability of the test to accurately predict distant recurrence
      free survival in this population. RESULTS: We identified 149 eligible patients.
      Median age at diagnosis was 59 years; mean tumor diameter was 2 cm; and 69% of
      tumors were estrogen receptor positive. Median follow-up was 18 years. The 5-year
      disease-free survival rate for the group was 80%. The 21 gene-based recurrence
      score was not predictive of distant disease recurrence. However, a high
      concordance between RT-PCR and immunohistochemical assays for estrogen receptor,
      progesterone receptor, and human epidermal growth factor receptor 2 status was
      noted. CONCLUSIONS: RT-PCR can be done on paraffin-embedded tissue to validate
      the large numbers of genes associated with breast cancer recurrence. However,
      further work needs to be done to develop an assay to identify the likelihood of
      recurrent disease in patients with node-negative breast cancer who do not receive
      adjuvant tamoxifen or chemotherapy.

PMID- 15867230
TI  - Human kallikrein 6: a new potential serum biomarker for uterine serous papillary
      cancer.
AB  - PURPOSE: The discovery of novel biomarkers might greatly contribute to improve
      clinical management and outcomes in uterine serous papillary carcinoma (USPC), a
      highly aggressive variant of endometrial cancer. EXPERIMENTAL DESIGN: Human
      kallikrein 6 (hK6) gene expression levels were evaluated in 29 snap-frozen
      endometrial biopsies, including 13 USPC, 13 endometrioid carcinomas, and 3 normal
      endometrial cells by real-time PCR. Secretion of hK6 protein by 14 tumor
      cultures, including 3 USPC, 3 endometrioid carcinoma, 5 ovarian serous papillary
      carcinoma, and 3 cervical cancers, was measured using a sensitive ELISA. Finally,
      hK6 concentration in 79 serum and plasma samples from 22 healthy women, 20 women
      with benign diseases, 20 women with endometrioid carcinoma, and 17 USPC patients
      was studied. RESULTS: hK6 gene expression levels were significantly higher in
      USPC when compared with endometrioid carcinoma (mean copy number by real-time
      PCR, 1,927 versus 239, USPC versus endometrioid carcinoma; P < 0.01). In vitro
      hK6 secretion was detected in all primary USPC cell lines tested (mean, 11.5
      microg/L) and the secretion levels were similar to those found in primary ovarian
      serous papillary carcinoma cultures (mean, 9.6 microg/L). In contrast, no hK6
      secretion was detectable in primary endometrioid carcinoma and cervical cancer
      cultures. hK6 serum and plasma concentrations (mean +/- SE) among normal healthy
      females (2.7 +/- 0.2 microg/L), patients with benign diseases (2.4 +/- 0.2
      microg/L), and patients with endometrioid carcinoma (2.6 +/- 0.2 microg/L) were
      not significantly different. In contrast, serum and plasma hK6 values in USPC
      patients (6.1 +/- 1.1) were significantly higher than those in the noncancer
      group (P = 0.006), benign group (P = 0.003), and endometrioid carcinoma patients
      (P = 0.005). CONCLUSIONS: hK6 is highly expressed in USPC and is released in the
      plasma and serum of USPC patients. hK6 may represent a novel biomarker for USPC
      for monitoring early disease recurrence and response to therapy.

PMID- 15867231
TI  - YKL-40 expression is associated with poorer response to radiation and shorter
      overall survival in glioblastoma.
AB  - PURPOSE: YKL-40 is a secreted protein that has been reported to be overexpressed
      in epithelial cancers and gliomas, although its function is unknown. Previous
      data in a smaller sample set suggested that YKL-40 was a marker associated with a
      poorer clinical outcome and a genetically defined subgroup of glioblastoma. Here
      we test these findings in a larger series of patients with glioblastoma, and in
      particular, determine if tumor YKL-40 expression is associated with radiation
      response. EXPERIMENTAL DESIGN: Patients (n=147) with subtotal resections were
      studied for imaging-assessed changes in tumor size in serial studies following
      radiation therapy. An additional set (n=140) of glioblastoma patients who
      underwent a gross-total resection was tested to validate the survival association
      and extend them to patients with minimal residual disease. RESULTS: In the
      subtotal resection group, higher YKL-40 expression was significantly associated
      with poorer radiation response, shorter time to progression and shorter overall
      survival. The association of higher YKL-40 expression with poorer survival was
      validated in the gross-total resection group. In multivariate analysis with both
      groups combined (n = 287), YKL-40 was an independent predictor of survival after
      adjusting for patient age, performance status, and extent of resection. YKL-40
      expression was also compared with genetically defined subsets of glioblastoma by
      assessing epidermal growth factor receptor amplification and loss at chromosome
      10q, two of the common recurring aberrations in these tumors, using fluorescent
      in situ hybridization. YKL-40 was significantly associated with 10q loss.
      CONCLUSIONS: The findings implicate YKL-40 as an important marker of therapeutic
      response and genetic subtype in glioblastomas and suggest that it may play an
      oncogenic role in these tumors.

PMID- 15867232
TI  - Phase I study of a novel taxane BMS-188797 in adult patients with solid
      malignancies.
AB  - PURPOSE: Preclinical studies show that BMS-188797 has a broad spectrum of
      antitumor activity in in vitro cytotoxicity assays and tumor xenograft models. We
      did a phase I trial designed to determine the maximum tolerated dose and the
      pharmacokinetics of BMS-188797 when administered i.v. MATERIALS AND METHODS: BMS
      188797 was administered i.v. over 60 minutes once every 21 days to 51 patients.
      The initial dose cohort of 3.75 mg/m(2) was set at approximately one third the
      lethal dose in dogs. Doses were subsequently escalated in cohorts according to a
      modified Fibonacci design. RESULTS: Fifty-one patients received a total of 160
      cycles of therapy. The dose-limiting toxicity of febrile neutropenia occurred in
      two patients at the 200 mg/m(2) cohort. Moderate to severe sensory neuropathy
      occurred in 12 patients (24%). Four radiographic partial responses based on the
      Response Evaluation Criteria in Solid Tumors occurred: two in subjects with
      breast cancer, one in a subject with non-small cell lung cancer, and one in a
      subject with renal cell carcinoma. The duration of the partial responses observed
      were 24.1 months (renal cell carcinoma), 5.7 and 4.3 months (breast cancer), and
      4.5 months (non-small cell lung cancer). Pharmacokinetics appear linear at doses
      through 110 mg/m(2) but not at higher doses. CONCLUSION: The dose-limiting
      toxicity in this single-agent study of BMS-188797 was febrile neutropenia. The
      recommended phase II dose of BMS-188797 as a single agent is 175 mg/m(2) i.v. for
      1 hour administered every 3 weeks.

PMID- 15867233
TI  - A phase I clinical trial of thoracic radiotherapy and concurrent celecoxib for
      patients with unfavorable performance status inoperable/unresectable non-small
      cell lung cancer.
AB  - OBJECTIVES: Preclinical observations that selective cyclooxygenase-2 inhibitors
      enhance in vitro cell radiosensitivity and in vivo tumor radioresponse led to
      clinical trials testing therapeutic efficacy of these agents. Our study was
      designed to determine whether the COX-2 inhibitor celecoxib could be safely
      administered in doses within those approved by the Food and Drug Administration
      when used concurrently with thoracic radiotherapy in patients with poor prognosis
      non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: The trial consisted of
      three cohorts of patients: (a) locally advanced NSCLC with obstructive pneumonia,
      hemoptysis, and/or minimal metastatic disease treated with 45 Gy in 15 fractions;
      (b) medically inoperable early-stage NSCLC treated with definitive radiation of
      66 Gy in 33 fractions; and (c) patients who received induction chemotherapy but
      who were not eligible for concurrent chemoradiotherapy trials. These patients
      received 63 Gy in 35 fractions. Celecoxib was administered p.o. on a daily basis
      5 days before and throughout the course of radiotherapy. Celecoxib doses were
      escalated from 200, 400, 600, to 800 mg/d given in two equally divided doses. Two
      to eight patients of each cohort were assigned to each dose level of celecoxib.
      RESULTS: Forty-seven patients were enrolled in this protocol (19 in cohort I, 22
      in cohort II, and 6 in cohort III). The main toxicities were grades 1 and 2
      nausea and esophagitis, and they were independent of the dose of celecoxib or
      radiotherapy schedule. Only two patients in group II developed grade 3
      pneumonitis 1 month after treatment, one on 200 mg, and the other on 400 mg
      celecoxib. Celecoxib-related toxicity developed in 3 of 47 patients: an
      uncontrolled hypertension in one patient on 800 mg celecoxib and hemorrhagic
      episodes in 2 patients (shoulder hematoma in one and hemoptysis in the other) on
      200 mg celecoxib who were on warfarin for other medical reasons. Of 37 patients
      evaluable for tumor response, 14 had complete response, 13 partial responses, and
      10 stable or progressive disease. The actuarial local progression-free survival
      was 66.0% at 1 year and 42.2% at 2 years following initiation of radiotherapy.
      CONCLUSIONS: These results show that celecoxib can be safely administered
      concurrently with thoracic radiotherapy when given up to the highest Food and
      Drug Administration-approved dose of 800 mg/d, which we used. A maximal tolerated
      dose was not reached in this study. The treatment resulted in actuarial local
      progression-free survival of 66.0% at 1 year and 42.2% at 2 years, an encouraging
      outcome that warrants further assessment in a phase II/III trial.

PMID- 15867234
TI  - High relapse rate in patients with MALT lymphoma warrants lifelong follow-up.
AB  - BACKGROUND: B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT
      lymphoma) is thought to be an indolent disease, with a good prognosis following
      various forms of treatment. Little, however, is known about the rate and pattern
      of relapse following successful treatment. PATIENTS AND METHODS: We have analyzed
      time to and pattern of relapse in patients with MALT lymphoma, along with
      investigation of t(11;18)(q21;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21)
      involving IGH/MALT1, trisomy 3, and trisomy 18. Eighty-six patients achieving
      complete remission (CR) after initial therapy with sufficient follow-up data were
      available. Primary site of disease was the stomach (n = 36), salivary gland (n =
      19), ocular adnexa/orbit (n = 12), lung (n = 8), thyroid (n = 5), breast (n = 3),
      liver (n = 2), and skin (n = 1). RESULTS: Thirty-two patients (37%) relapsed
      between 14 and 307 months (median 47 months) after initial CR. Ten relapses were
      local, whereas the remaining patients relapsed in a distant organ. Eight of 36
      gastric versus 24 of 50 nongastric MALT lymphomas (P = 0.02) relapsed. Five
      patients had a second recurrence 26 to 56 months after a second CR. Relapse rates
      were not related to forms of initial treatment. Chromosomal aberrations were
      detected in 14 of 28 (50%) relapsing patients, and chromosomal alterations were
      identical at diagnosis and relapse. No significant association of any of the
      genetic changes investigated with relapse was found. Interestingly, patients with
      t(11;18)(q21;q21) had a significantly longer median time to relapse (76 months)
      than patients without this translocation (29 months; P = 0.012). CONCLUSIONS: In
      view of the late relapses seen in our series, lifelong observation of all
      patients treated for MALT lymphoma seems to be required.

PMID- 15867235
TI  - Combining a recombinant cancer vaccine with standard definitive radiotherapy in
      patients with localized prostate cancer.
AB  - PURPOSE: Many patients with clinically localized prostate cancer develop
      biochemical failure despite excellent local therapy perhaps due to occult
      metastatic disease. One potential solution is the utilization of a well-tolerated
      systemic therapy (e.g., vaccine) in concert with local therapy. EXPERIMENTAL
      DESIGN: We present a randomized phase II clinical trial designed to determine if
      a poxviral vaccine encoding prostate-specific antigen (PSA) can induce a PSA
      specific T-cell response when combined with radiotherapy in patients with
      clinically localized prostate cancer. Thirty patients were randomized in a 2:1
      ratio into vaccine plus radiotherapy or radiotherapy-only arms. Those patients in
      the combination arm received a "priming" vaccine with recombinant vaccinia (rV)
      PSA plus r V containing the T-cell costimulatory molecule B7.1 (rV-B7.1) followed
      by monthly booster vaccines with recombinant fowlpox PSA. The vaccines were given
      with local granulocyte-macrophage colony-stimulating factor and low-dose systemic
      interleukin-2. Standard external beam radiation therapy was given between the
      fourth and the sixth vaccinations. RESULTS: Seventeen of 19 patients in the
      combination arm completed all eight vaccinations and 13 of these 17 patients had
      increases in PSA-specific T cells of at least 3-fold versus no detectable
      increases in the radiotherapy-only arm (P < 0.0005). There was also evidence of
      de novo generation of T cells to well-described prostate-associated antigens not
      found in the vaccine, providing indirect evidence of immune-mediated tumor
      killing. The vaccine was well tolerated. CONCLUSION: This vaccine regimen can be
      safely given in patients undergoing radiation therapy for localized prostate
      cancer, with the majority of patients generating a PSA-specific cellular immune
      response to vaccine.

PMID- 15867236
TI  - Intratumoral COX-2 gene expression is a predictive factor for colorectal cancer
      response to fluoropyrimidine-based chemotherapy.
AB  - PURPOSE: Cyclooxygenase-2 (COX-2) is generally elevated in tumors compared with
      normal tissue and apparently has an important role in tumor development. A number
      of studies have found high expression of COX-2 to be an unfavorable prognostic
      factor for overall survival in several cancers. However, the influence of COX-2
      expression levels on tumor response to chemotherapy has been relatively little
      studied. The purpose of this study was to ascertain if COX-2 gene expression is
      associated with tumor response in the clinical treatment of colorectal cancer
      with the fluoropyrimidine-based therapy S-1. EXPERIMENTAL DESIGN: Patients with
      advanced (stage IV) colorectal cancer were treated with S-1 twice daily based on
      the patient's body surface area (BSA; BSA < 1.25 m2, 80 mg/d; 1.25 m2 < or = BSA
      < 1.5 m2, 100 mg/d; BSA > or = 1.5 m2, 120 mg/d) for 28 days followed by a 2-week
      period rest. mRNA was isolated from paraffin-embedded pretreatment primary tumor
      specimens and expression levels of COX-2 relative to beta-actin as the internal
      reference gene were measured using a quantitative reverse transcription-PCR
      (Taqman) system. RESULTS: The overall response rate in a group of 44 patients
      treated with S-1 was 40.9%. Sufficient tumor tissue was available from 40 of
      these patients for COX-2 mRNA quantitation. COX-2 gene expression was
      significantly lower in the responding tumors compared with the nonresponders (P =
      0.012, Wilcoxon test). Patients with COX-2 values above the cutoff value of 3.28
      x 10(-3) had a significantly shorter survival than those with COX-2 gene
      expressions below the cutoff value (adjusted P = 0.031). CONCLUSIONS:
      Intratumoral COX-2 gene expression is associated with likelihood of response to
      chemotherapy with S-1 and is a prognostic factor for survival of patients after
      the start of S-1 chemotherapy.

PMID- 15867237
TI  - A multicenter phase II trial of ZD6474, a vascular endothelial growth factor
      receptor-2 and epidermal growth factor receptor tyrosine kinase inhibitor, in
      patients with previously treated metastatic breast cancer.
AB  - PURPOSE: To determine the efficacy and safety of ZD6474, an orally available
      inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine
      kinase with additional activity against the epidermal growth factor receptor
      (EGFR) tyrosine kinase, in patients with previously treated metastatic breast
      cancer. PATIENTS AND METHODS: Eligible patients had histologically confirmed
      metastatic breast cancer and had received prior treatment with an anthracycline
      and taxane; measurable disease was required. Patients were enrolled sequentially
      into one of two dose cohorts, 100 or 300 mg orally once daily; 28 days defined
      one cycle. The primary end point was objective response rate; pharmacokinetics
      and serial pharmacodynamic studies were obtained. RESULTS: Forty-six patients
      were enrolled between May 2002 and April 2003, and 44 were evaluable for
      response. Diarrhea was the most commonly reported toxicity and seemed dose
      related (grade >/=2: 4.5% and 37.5% in the 100 and 300 mg cohorts, respectively).
      Rash was reported by 26% of patients but was never worse than grade 2. Seven
      patients in the 300 mg cohort had asymptomatic grade 1 prolongation of the QTc
      interval. Hypertension requiring treatment was not reported. There were no
      objective responses; one patient in the 300 mg cohort had stable disease >/=24
      weeks. All patients in the 300 mg cohort and 90% of patients in the 100 mg cohort
      achieved steady-state concentrations exceeding the IC(50) for VEGF inhibition in
      preclinical models. CONCLUSION: ZD6474 monotherapy was generally well tolerated
      but had limited monotherapy activity in patients with refractory metastatic
      breast cancer.

PMID- 15867238
TI  - Generation of potent antitumor CTL from patients with multiple myeloma directed
      against HM1.24.
AB  - PURPOSE: The purpose of this work was to test the suitability of the HM1.24
      antigen as a CTL target for immunotherapy of patients with multiple myeloma.
      EXPERIMENTAL DESIGN: Antigen-specific T cells were generated from patients with
      multiple myeloma using stimulation with protein-pulsed dendritic cells and tested
      in ELISPOT and CTL assays. RESULTS: HM1.24-primed T cells responded selectively
      to HM1.24-loaded autologous peripheral blood mononuclear cells (PBMC) in an IFN
      gamma ELISPOT assay (median, 342; range, 198-495 IFN-gamma-producing cells/10(5)
      cf. unloaded PBMC median, 98; range, 7-137; P < 0.05, n = 5) and also to
      autologous malignant plasma cells (MPC; median, 227; range, 153-335; P < 0.05
      when compared with the response to allogeneic MPC median, 57; range, 22-158; n =
      5). HM1.24-primed T cells lysed autologous MPC (at 20:1 E/T ratio: median, 48%
      specific killing; range, 23-88%; at 10:1 E/T ratio: median, 43%; range, 15-80%; n
      = 12) but not allogeneic MPC. Lysis of autologous MPC was inhibited by anti-MHC
      class I but not anti-MHC class II antibodies and was blocked by Concanamycin A.
      Lysis of autologous MPC was blocked by competition with autologous HM1.24
      transfected dendritic cells (10:1 ratio with autologous MPC). Unmanipulated, or
      control plasmid-transfected dendritic cells had no effect on lysis of autologous
      MPC. CONCLUSION: Our results indicate that HM1.24 is a promising target for
      immunotherapy of multiple myeloma.

PMID- 15867239
TI  - Phase I pharmacokinetic-pharmacodynamic study of 17-(allylamino)-17
      demethoxygeldanamycin (17AAG, NSC 330507), a novel inhibitor of heat shock
      protein 90, in patients with refractory advanced cancers.
AB  - PURPOSE: 17-(Allylamino)-17-demethoxygeldanamycin (17AAG), a benzoquinone
      antibiotic, down-regulates oncoproteins by binding specifically to heat shock
      protein 90 (HSP90). We did a phase I study of 17AAG to establish the dose
      limiting toxicity and maximum tolerated dose and to characterize 17AAG
      pharmacokinetics and pharmacodynamics. EXPERIMENTAL DESIGN: Escalating doses of
      17AAG were given i.v. over 1 or 2 hours on a weekly x 3 schedule every 4 weeks to
      cohorts of three to six patients. Plasma pharmacokinetics of 17AAG and 17-(amino)
      17-demethoxygeldanamycin (17AG) were assessed by high-performance liquid
      chromatography. Expression of HSP70 and HSP90 in peripheral blood mononuclear
      cells was measured by Western blot. RESULTS: Forty-five patients were enrolled to
      11 dose levels between 10 and 395 mg/m2. The maximum tolerated dose was 295
      mg/m2. Dose-limiting toxicity occurred in both patients (grade 3 pancreatitis and
      grade 3 fatigue) treated with 395 mg/m2. Common drug-related toxicities (grade 1
      and 2) were fatigue, anorexia, diarrhea, nausea, and vomiting. Reversible
      elevations of liver enzymes occurred in 29.5% of patients. Hematologic toxicity
      was minimal. No objective responses were observed. 17AAG pharmacokinetics was
      linear. Peak plasma concentration and area under the curve of 17AG, the active
      major metabolite of 17AAG, increased with 17AAG dose, but the relationships were
      more variable than with 17AAG. 17AAG and 17AG in plasma were >90% protein bound.
      There were no consistent changes in peripheral blood mononuclear cell HSP90 or
      HSP70 content. CONCLUSIONS: 17AAG doses between 10 and 295 mg/m2 are well
      tolerated. 17AAG pharmacokinetics is linear. Peripheral blood mononuclear cell
      HSP90 and HSP70 are uninformative pharmacodynamic markers. The dose recommended
      for future studies is 295 mg/m2 weekly x 3, repeated every 4 weeks.

PMID- 15867240
TI  - Enhanced pharmacodynamic and antitumor properties of a histone deacetylase
      inhibitor encapsulated in liposomes or ErbB2-targeted immunoliposomes.
AB  - ErbB2-overexpressing human cancers represent potentially sensitive targets for
      therapy by candidate histone deacetylase (HDAC) inhibitors as we have shown that
      HDAC inhibitors can selectively reduce ErbB2 expression by repressing the ErbB2
      promoter and accelerating the decay of cytoplasmic ErbB2 transcripts. To extend
      these in vitro findings and enhance the in vivo pharmacodynamic properties of
      HDAC inhibitors, we stably encapsulated a potent hydroxamate-based HDAC inhibitor
      (LAQ824) within long-circulating liposomes (Ls-LAQ824) and immunoliposomes (ILs
      LAQ824) bearing >10,000 LAQ824 molecules per nanovesicle. Liposomal LAQ824
      exhibits prolonged in vivo stability and, unlike free LAQ824, circulates with a
      half-life of 10.8 hours following a single i.v. injection. Three weekly i.v.
      injections of 20 to 25 mg/kg Ls-LAQ824 in nude mice with ErbB2 overexpressing BT
      474 breast tumor xenografts significantly impairs tumor growth, and
      administration of ErbB2-targeted ILs-LAQ824 may further improve this antitumor
      activity. Studies of tumor-bearing mice 24 hours after single treatment indicate
      that: (a) >10% of injected liposomal LAQ824 is still circulating (whereas free
      LAQ824 is undetectable in the blood after 15 minutes); and (b) tumor uptake of Ls
      LAQ824 and ILs-LAQ824 is >3% injected drug per gram of tumor, producing levels of
      acetylated tumor histones that are 5- to 10-fold increased over those following
      free LAQ824 or saline treatments and resulting in concordantly reduced levels of
      tumor ErbB2 mRNA. These preclinical results support the clinical evaluation of
      HDAC inhibitors against ErbB2-overexpressing malignancies, and further indicate
      that encapsulation into targeted and nontargeted liposomes substantially improves
      the in vivo pharmacokinetics, tumor uptake, and antitumor properties of
      hydroxamate-based HDAC inhibitors.

PMID- 15867241
TI  - Temozolomide pharmacodynamics in patients with metastatic melanoma: dna damage
      and activity of repair enzymes O6-alkylguanine alkyltransferase and poly(ADP
      ribose) polymerase-1.
AB  - PURPOSE: Temozolomide, a DNA methylating agent used to treat melanoma, induces
      DNA damage, which is repaired by O6-alkylguanine alkyltransferase (ATase) and
      poly(ADP-ribose) polymerase-1 (PARP-1)-dependent base excision repair. The
      current study was done to define the effect of temozolomide on DNA integrity and
      relevant repair enzymes as a prelude to a phase I trial of the combination of
      temozolomide with a PARP inhibitor. EXPERIMENTAL DESIGN: Temozolomide (200 mg/m2
      oral administration) was given to 12 patients with metastatic malignant melanoma.
      Peripheral blood lymphocytes (PBL) were analyzed for PARP activity, DNA single
      strand breakage, ATase levels, and DNA methylation. PARP activity was also
      measured in tumor biopsies from 9 of 12 patients and in PBLs from healthy
      volunteers. RESULTS: Temozolomide pharmacokinetics were consistent with previous
      reports. Temozolomide therapy caused a substantial and sustained elevation of N7
      methylguanine levels, a modest and sustained reduction in ATase activity, and a
      modest and transient increase in DNA strand breaks and PARP activity in PBLs.
      PARP-1 activity in tumor homogenates was variable (828 +/- 599 pmol PAR
      monomer/mg protein) and was not consistently affected by temozolomide treatment.
      CONCLUSIONS: The effect of temozolomide reported here are consistent with those
      documented in previous studies with temozolomide and similar drug, dacarbazine,
      demonstrating that a representative patient population was investigated.
      Furthermore, PARP activity was not inhibited by temozolomide treatment and this
      newly validated pharmacodynamic assay is therefore suitable for use in a proof-of
      principle phase I trial a PARP-1 inhibitor in combination with temozolomide.

PMID- 15867242
TI  - A phase I and pharmacologic trial of two schedules of the proteasome inhibitor,
      PS-341 (bortezomib, velcade), in patients with advanced cancer.
AB  - PURPOSE: To define the toxicities, pharmacodynamics, and clinical activity of the
      proteasome inhibitor, PS-341 (bortezomib), in patients with advanced
      malignancies. PATIENTS AND METHODS: Twenty-eight patients (14 male and 14 female)
      received PS-341 twice weekly for 4 of 6 weeks (schedule I). Because toxicity
      necessitated dose omissions on this schedule, 16 additional patients (12 male and
      4 female) received PS-341 twice weekly for 2 of every 3 weeks (schedule II). A
      total of 73 courses of treatment was given (median, 2; range, 1-4). Inhibition of
      20S proteasome activity in peripheral blood mononuclear cells (PBMC) and
      accumulation of proteasome-targeted polypeptides in tumor tissue were evaluated
      as pharmacodynamic markers of PS-341 activity. RESULTS: The most common toxicity
      was thrombocytopenia, which was dose limiting at 1.7 mg/m2 (schedule I) and 1.6
      mg/m2 (schedule II), respectively. Sensory neuropathy was dose-limiting in a
      patient in schedule I. Grade > or =3 toxicities for schedule I were constipation,
      fatigue, myalgia, and sensory neuropathy. Grade > or =3 toxicities for schedule
      II were dehydration resulting from diarrhea, nausea and vomiting, fatigue,
      hypoglycemia, and hypotension. The maximum tolerated dose was 1.5 mg/m2 for both
      schedules. Reversible dose-dependent decreases in 20S proteasome activity in
      PBMCs were observed, with 36% inhibition at 0.5 mg/m2, 52% at 0.9 mg/m2, and 75%
      at 1.25 mg/m2. Accumulation of proteasome-targeted polypeptides was detected in
      tumor samples after treatment with PS-341. A patient with multiple myeloma had a
      partial response. CONCLUSION: PS-341 given 1.5 mg/m2 twice weekly for 2 of every
      3 weeks is well tolerated and should be further studied.

PMID- 15867243
TI  - Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with
      carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
AB  - PURPOSE: Marimastat is an orally bioavailable inhibitor of matrix
      metalloproteinases. A phase I study was initiated to determine whether
      conventional doses of carboplatin and paclitaxel are tolerated when combined with
      marimastat and to assess the influence of marimastat on paclitaxel
      pharmacokinetics. EXPERIMENTAL DESIGN: Three dose levels were evaluated.
      Marimastat (10 or 20 mg oral administration b.i.d.) was administered continuously
      with paclitaxel (175 or 200 mg/m(2) as a 3-hour i.v. infusion) and carboplatin
      (at a dose providing an area under the free drug plasma concentration-time curve
      of 7 mg min/mL) administered each 3 weeks. Toxicity and response were evaluated
      throughout the intended four cycles of combined therapy. The plasma
      pharmacokinetics of paclitaxel was determined in each patient both without
      concurrent marimastat and after receiving marimastat for 1 week. RESULTS: Twenty
      two chemotherapy-naive patients with stage IIIb (27%) or stage IV (73%) non-small
      cell lung cancer were enrolled. Their median age was 56 years (range, 39-73
      years), 50% were female, and their performance status (Eastern Cooperative
      Oncology Group) ranged from 0 to 2. Treatment was well tolerated, as 18 (82%) of
      the patients completed all four cycles of chemotherapy without dose-limiting
      toxicity. Grade 2 musculoskeletal toxicities were reported in 3 of 12 patients
      receiving marimastat (20 mg b.i.d.). Nine patients required dose reductions,
      predominantly related to low-grade myelosuppression. Partial responses occurred
      in 12 of 21 (57%) evaluable patients with disease stabilization in another 5
      (19%). Marimastat had no effect on paclitaxel pharmacokinetics. CONCLUSIONS: The
      administration of marimastat (10 mg b.i.d.) with paclitaxel (200 mg/m(2)) and
      carboplatin at an area under the free drug plasma concentration-time curve of 7
      mg min/mL was well tolerated with no apparent pharmacokinetic interaction. Study
      of this drug combination in the adjuvant setting should be considered if tissue
      inhibition of matrix metalloproteinase activity can first be shown.

PMID- 15867244
TI  - Molecular responses in patients with chronic myelogenous leukemia in chronic
      phase treated with imatinib mesylate.
AB  - PURPOSE: To determine the clinical significance of molecular response and relapse
      among patients with chronic myelogenous leukemia (CML) treated with imatinib.
      EXPERIMENTAL DESIGN: We analyzed the results of quantitative PCR in 280 patients
      with CML in chronic phase who achieved complete cytogenetic remission with
      imatinib (117 after IFN-alpha failure and 163 previously untreated). Median
      follow-up was 31 months (range, 3-52 months). RESULTS: Median BCR-ABL/ABL ratio
      before the start of therapy was 39.44 (range, 0.252-170.53). A major molecular
      response (BCR-ABL/ABL ratio <0.05%) was achieved in 174 (62%), and transcripts
      became undetectable (complete molecular response) in 95 (34%). By multivariate
      analysis, only treatment with high-dose imatinib (P = 0.02) was associated with
      achievement of a major molecular response. Nine of 166 (5%) patients who achieved
      a major molecular response lost their cytogenetic remission, compared with 25 of
      68 (37%) among those who did not achieve this response (P < 0.0001). Patients
      achieving a major molecular response 12 months after the start of therapy had
      significantly better complete cytogenetic remission duration than others. A >1
      log reduction in transcript levels after 3 months of therapy predicted for an
      improved probability of achieving a major molecular response at 24 months.
      Increasing levels of BCR-ABL transcripts predicted for a loss of cytogenetic
      remission only among patients who did not achieve a major molecular response.
      CONCLUSIONS: Achieving a major molecular response, particularly within the first
      year of therapy, is predictive of a durable cytogenetic remission and may be the
      future goal of therapy in CML.

PMID- 15867245
TI  - RNA interference demonstrates a novel role for integrin-linked kinase as a
      determinant of pancreatic adenocarcinoma cell gemcitabine chemoresistance.
AB  - Integrin-linked kinase (ILK) facilitates signal transduction between
      extracellular events and important intracellular survival pathways involving
      protein kinase B/Akt. We examined the role of ILK in determining pancreatic
      adenocarcinoma cellular chemoresistance to the nucleoside analogue gemcitabine.
      Cellular ILK expression was quantified by Western blot analysis. We examined the
      effects of overexpression of active ILK and of ILK knockdown induced by RNA
      interference on gemcitabine chemoresistance. We also examined the effects of
      modulating ILK expression on gemcitabine-induced caspase 3-mediated apoptosis,
      phosphorylation status of Akt (Ser473) and glycogen synthase kinase.
      Overexpression of ILK increased cellular gemcitabine chemoresistance, whereas ILK
      knockdown induced chemosensitization via increased caspase 3-mediated apoptosis.
      ILK knockdown attenuated Akt Ser473 and glycogen synthase kinase phosphorylation,
      whereas overexpression of constitutively active myristoylated Akt was sufficient
      to induce significant recovery in gemcitabine chemoresistance in the presence of
      ILK knockdown. Levels of ILK expression affect gemcitabine chemoresistance in
      pancreatic adenocarcinoma cells. This novel finding suggests that therapies
      directed against ILK and its downstream signaling targets may have the potential
      to enhance the efficacy of gemcitabine-based chemotherapy.

PMID- 15867246
TI  - Resistance to the tubulin-binding agents in renal cell carcinoma: no mutations in
      the class I beta-tubulin gene but changes in tubulin isotype protein expression.
AB  - PURPOSE: The primary purpose of this study was to determine whether mutations of
      the class I beta-tubulin gene may be implicated in the inherent resistance to
      tubulin-binding agents (TBA) in renal cancer, with a small number of samples and
      cell lines also being examined for class I and III beta-tubulin isotype protein
      expression. EXPERIMENTAL DESIGN: DNA was extracted from 90 renal tumors and the
      class I beta-tubulin gene analyzed for mutations. For each sample, eight PCRs
      were used to cover the complete coding sequence with intronic primers ensuring
      highly homologous pseudogenes were not coamplified. Additionally, expression
      levels of class I and III beta-tubulin isotypes in 17 matched normal and
      malignant renal samples and a panel of renal cell carcinoma cell lines with
      differing intrinsic resistance to the TBAs was examined by Western blotting.
      RESULTS: Four polymorphic sequence changes of the class I beta-tubulin gene were
      identified with no mutations. Class I protein expression levels were higher in
      tumor tissue versus normal tissue, whereas class III expression showed no
      consistent change. In renal cancer cell lines, a significant correlation between
      class III isotype expression and vinblastine sensitivity was observed.
      CONCLUSIONS: These results do not support a role for mutations in the class I
      beta-tubulin gene in the intrinsic resistance of renal cancer to TBAs. Class III
      isotype expression may be implicated in resistance in vitro but in vivo, changes
      in class I isotype expression in renal cell carcinoma tissue may support a role
      in resistance to the TBAs and warrants further investigation.

PMID- 15867247
TI  - Definition of an immunogenic region within the ovarian tumor antigen stratum
      corneum chymotryptic enzyme.
AB  - PURPOSE: The serine protease stratum corneum chymotryptic enzyme (SCCE) is
      overexpressed by ovarian tumor cells, but is not expressed by normal tissues,
      suggesting that SCCE may be an attractive target for immunotherapy. In this
      study, we tested the hypothesis that dendritic cells loaded with SCCE peptides
      will induce ovarian tumor antigen-specific CD8+ CTL responses and antigen
      specific CD4+ helper T cell responses. EXPERIMENTAL DESIGN: Computer algorithms
      were used to identify candidate HLA-A2.1-restricted CD8+ CTL epitopes and HLA-DR
      binding CD4+ helper T cell epitopes within SCCE. CD8+ CTL stimulated with peptide
      loaded dendritic cells were tested against targets expressing endogenous SCCE,
      including HLA-A2.1-matched ovarian tumor cells. Dendritic cells were also loaded
      with an extended SCCE peptide, SCCE 110-139, which encompassed a defined CD8+ CTL
      epitope and multiple candidate CD4+ T helper cell epitopes. RESULTS: CD8+ CTL
      specific for SCCE 123-131 lysed autologous macrophages infected with an SCCE
      expressing recombinant adenovirus, and also lysed HLA-A2.1-matched, SCCE
      expressing ovarian tumor cells. Dendritic cells loaded with SCCE 5-13 peptide
      stimulated an HLA-A2.1-restricted CD8+ CTL response, but with a reduced level of
      lysis against ovarian tumor cells. Dendritic cells loaded with SCCE 110-139
      induced antigen-specific CD4+ T cell and CD8+ T cell responses. Although SCCE 110
      139-loaded dendritic cells processed and presented the 123-131 epitope, the
      dominant CD8+ CTL response was directed against alternative epitopes within SCCE
      110-139. CONCLUSIONS: The 110-139 region of SCCE incorporates multiple CD8+ CTL
      and CD4+ helper T cell epitopes, and represents an attractive target antigen for
      immunotherapy of ovarian cancer.

PMID- 15867248
TI  - Antimetastatic effect of salvicine on human breast cancer MDA-MB-435 orthotopic
      xenograft is closely related to Rho-dependent pathway.
AB  - PURPOSE: Salvicine is a novel DNA topoisomerase II inhibitor with potent
      anticancer activity. In present study, the effect of salvicine against metastasis
      is evaluated using human breast carcinoma orthotopic metastasis model and its
      mechanism is further investigated both in animal and cellular levels.
      EXPERIMENTAL DESIGN: The MDA-MB-435 orthotopic xenograft model was applied to
      detect the antimetastatic effect of salvicine. Potential target candidates were
      detected and analyzed by microarray technology. Candidates were verified and
      explored by reverse transcription-PCR and Western blot. Salvicine activities on
      stress fiber formation, invasion, and membrane translocation were further
      investigated by immunofluorescence, invasion, and ultracentrifugal assays.
      RESULTS: Salvicine significantly reduced the lung metastatic foci of MDA-MB-435
      orthotopic xenograft, without affecting primary tumor growth obviously. A
      comparison of gene expression profiles of primary tumors and lung metastatic
      focus between salvicine-treated and untreated groups using the CLOTECH Atlas
      human Cancer 1.2 cDNA microarray revealed that genes involved in tumor
      metastasis, particularly those closely related to cell adhesion and motility,
      were obviously down-regulated, including fibronectin, integrin alpha3, integrin
      beta3, integrin beta5, FAK, paxillin, and RhoC. Furthermore, salvicine
      significantly down-regulated RhoC at both mRNA and protein levels, greatly
      inhibited stress fiber formation and invasiveness of MDA-MB-435 cells, and
      markedly blocked translocation of both RhoA and RhoC from cytosol to membrane.
      CONCLUSION: The unique antimetastatic action of salvicine, particularly its
      specific modulation of cell motility in vivo and in vitro, is closely related to
      Rho-dependent signaling pathway.

PMID- 15867249
TI  - Systemic delivery of liposomal short-chain ceramide limits solid tumor growth in
      murine models of breast adenocarcinoma.
AB  - In vitro tumor cell culture models have illuminated the potential therapeutic
      utility of elevating the intracellular concentration of the antimitogenic and
      proapoptotic sphingolipid, ceramide. However, although cell-permeable, short
      chain ceramide is an effective apoptotic agent in vitro, its use as an in vivo,
      systemically delivered therapeutic is limited by its inherent lipid
      hydrophobicity and physicochemical properties. Here, we report that the systemic
      i.v. delivery of C6-ceramide (C6) in a pegylated liposomal formulation
      significantly limited the growth of solid tumors in a syngeneic BALB/c mouse
      tumor model of breast adenocarcinoma. Over a 3-week treatment period, a well
      tolerated dose of 36 mg/kg liposomal-C6 elicited a >6-fold reduction in tumor
      size compared with empty ghost liposomes. Histologic analyses of solid tumors
      from liposomal-C6-treated mice showed a marked increase in the presence of
      apoptotic cells, with a coincident decrease in cellular proliferation and in the
      development of a microvessel network. Liposomal-C6 accumulated within caveolae
      and mitochondria, suggesting putative mechanisms by which ceramide induces
      selective cancer cell cytotoxicity. A pharmacokinetic analysis of systemic
      liposomal-C6 delivery showed that the pegylated liposomal formulation follows
      first-order kinetics in the blood and achieves a steady-state concentration in
      tumor tissue. Confirming the therapeutic utility of i.v. liposomal-C6
      administration, we also shown diminution of solid tumor growth in a human
      xenograft model of breast cancer. Together, these results indicate that bioactive
      ceramide analogues can be incorporated into pegylated liposomal vehicles for
      improved solubility, drug delivery, and antineoplastic efficacy.

PMID- 15867250
TI  - The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and
      in vivo.
AB  - PURPOSE: In this study, we have examined the antitumor effects of chloroform
      extract of Angelica sinensis (AS-C), a traditional Chinese medicine, on
      glioblastoma multiforme (GBM) brain tumors in vitro and in vivo. EXPERIMENTAL
      DESIGN: In vitro, GBM cells were treated with AS-C, and the cell proliferation,
      changes in distributions of cell cycle, and apoptosis were determined. In vivo,
      human DBTRG-05MG and rat RG2 GBM tumor cells were injected s.c. or i.c. and were
      treated with AS-C. Effects on tumor growth were determined by tumor volume,
      magnetic resonance imaging, survival, and histology analysis. RESULTS: The AS-C
      displays potency in suppressing growth of malignant brain tumor cells without
      cytotoxicity to fibroblasts. Growth suppression of malignant brain tumor cells by
      AS-C results from cell cycle arrest and apoptosis. AS-C can up-regulate
      expression of cdk inhibitors, including p21, to decrease phosphorylation of Rb
      proteins resulting in cell arrest at the G0-G1 phase for DBTRG-05MG and RG2
      cells. The apoptosis-associated proteins are dramatically increased and activated
      in DBTRG-05MG cells and RG2 cells by AS-C but RG2 cells without p53 protein
      expression. In vitro results showed AS-C triggered both p53-dependent and p53
      independent pathways for apoptosis. In in vivo studies, AS-C not only can
      suppress growths of malignant brain tumors of rat and human origin but also
      shrink the volumes of in situ GBM, significantly prolonging survivals.
      CONCLUSIONS: The in vitro and in vivo anticancer effects of AS-C indicate that it
      has sufficient potential to warrant further investigation and development as a
      new anti-brain tumor agent.

PMID- 15867251
TI  - Sensitivity to gemcitabine and its metabolizing enzymes in neuroblastoma.
AB  - PURPOSE: We examined the activity of gemcitabine against neuroblastoma in vitro
      and in vivo. In addition, we investigated the cellular mechanisms of high
      sensitivity to the agent in neuroblastoma cells. EXPERIMENTAL DESIGN: We examined
      11 neuroblastoma cell lines for sensitivity to gemcitabine and other
      chemotherapeutic agents used clinically for neuroblastoma. The in vivo
      sensitivity of neuroblastoma to gemcitabine was determined in xenograft models.
      Furthermore, the major metabolic enzymes of gemcitabine were assessed and
      compared in leukemia and carcinoma cells. Apoptosis and mitochondrial membrane
      potentials were also evaluated. RESULTS: The IC50s for gemcitabine in 11
      neuroblastoma lines ranged between 3 nmol/L and 4 micromol/L. The high activity
      of gemcitabine against neuroblastoma was confirmed in animal models.
      Interestingly, enzymes in neuroblastoma cells involved in the metabolism of
      deoxycytidine analogue have unique characteristics among solid tumors. The median
      of deoxycytidine kinase activity in neuroblastoma lines was similar to that in
      leukemia lines, which have low IC50s for cytarabine. Cytidine deaminase (CDA)
      activity in neuroblastoma was hardly detectable and significantly lower than that
      in carcinoma. The defect of CDA activity was associated with negative expression
      of mRNA. Furthermore, gemcitabine-induced apoptosis was observed irrespective of
      the caspase-8 status of neuroblastoma cells, which indicates that apoptosis
      depends on the mitochondrial pathway. CONCLUSIONS: Neuroblastoma is highly
      sensitive to gemcitabine. Although the cellular mechanism involved in sensitivity
      to gemcitabine is multifactorial, low CDA activity may contribute high
      sensitivity in neuroblastoma cells. These results suggest that clinical
      application of gemcitabine to the treatment of neuroblastoma is warranted.

PMID- 15867252
TI  - Blockade of paracrine supply of insulin-like growth factors using neutralizing
      antibodies suppresses the liver metastasis of human colorectal cancers.
AB  - Environmental stimuli, such as organ-specific growth factors, can influence the
      metastatic potential of a tumor. The liver is the main source of insulin-like
      growth factors (IGFs). The importance of IGF signal in hepatic metastasis has
      been clarified mainly by IGF-I receptor targeting strategies. This study aims to
      confirm these precedent reports by novel tool, neutralizing antibodies against
      IGFs and to show that IGFs are promising therapeutic targets for hepatic
      metastasis in vivo. Hepatic metastasis was induced by intrasplenic injection of
      human colorectal cancer cell line, HT29. The antimetastatic effects of three
      antibodies (anti-mouse IGF-I, anti-mouse IGF-II, and anti-human/mouse IGF-II
      designated KM1468) were tested singly or in combination in the early phase of
      metastasis. The dose escalation effect of KM1468 and its survival benefit were
      examined in the early and late phases of metastasis. The mechanism of IGF
      neutralization was investigated with immunohistochemistry. Dual neutralization of
      paracrine IGF-I and IGF-II showed modest additive antimetastatic effects than
      single neutralization of IGF-I or IGF-II. In any phase of metastasis,
      neutralization led to significant tumor growth inhibition and longer survival.
      Dose escalation of KM1468 influenced survival only in the late phase of
      metastasis. Apoptosis increased significantly in the antibody-treated group
      compared with the control group (P = 0.0025) In conclusion, IGFs are promising
      therapeutic targets for hepatic metastases of colorectal cancers. However, the
      IGF dependency is probably variable in the metastatic process.

PMID- 15867253
TI  - Metabolic signatures associated with a NAD synthesis inhibitor-induced tumor
      apoptosis identified by 1H-decoupled-31P magnetic resonance spectroscopy.
AB  - PURPOSE: Attempts to selectively initiate tumor cell death through inducible
      apoptotic pathways are increasingly being exploited as a potential anticancer
      strategy. Inhibition of NAD+ synthesis by a novel agent FK866 has been recently
      reported to induce apoptosis in human leukemia, hepatocarcinoma cells in vitro,
      and various types of tumor xenografts in vivo. In the present study, we used 1H
      decoupled phosphorus (31P) magnetic resonance spectroscopy (MRS) to examine the
      metabolic changes associated with FK866 induced tumor cell death in a mouse
      mammary carcinoma. EXPERIMENTAL DESIGN: Induction of apoptosis in FK866-treated
      tumors was confirmed by histology and cytofluorometric analysis. FK866-induced
      changes in mammary carcinoma tumor metabolism in vivo were investigated using 1H
      decoupled 31P MRS. To discern further the changes in metabolic profiles of tumors
      observed in vivo, high-resolution in vitro 1H-decoupled 31P MRS studies were
      carried out with perchloric acid extracts of mammary carcinoma tumors excised
      after similar treatments. In addition, the effects of FK866 on mammary carcinoma
      tumor growth and radiation sensitivity were studied. RESULTS: Treatment with
      FK866 induced a tumor growth delay and enhanced radiation sensitivity in mammary
      carcinoma tumors that was associated with significant increases in the 31P MR
      signal in the phosphomonoester region and a decrease in NAD+ levels, pH, and
      bioenergetic status. The 31P MRS of perchloric acid extracts of treated tumors
      identified the large unresolved signal in the phosphomonoester region as the
      resultant of resonances originating from intermediates of tumor glycolysis and
      guanylate synthesis in addition to alterations in pyridine nucleotide pools and
      phospholipid metabolism. CONCLUSION: The present results suggest that FK866
      interferes with multiple biochemical pathways that contribute to the increased
      cell death (apoptosis) and subsequent radiation sensitivity observed in the
      mammary carcinoma that could be serially monitored by 31P MRS.

PMID- 15867254
TI  - Differential effects of vascular endothelial growth factor receptor-2 inhibitor
      ZD6474 on circulating endothelial progenitors and mature circulating endothelial
      cells: implications for use as a surrogate marker of antiangiogenic activity.
AB  - PURPOSE: Circulating endothelial cells (CEC) comprise at least two distinct
      populations: bone marrow-derived circulating endothelial progenitors (CEP) and
      mature CECs derived from existing vasculature. We hypothesized that
      antiangiogenic agents may have differential effects on CEPs and mature CECs and
      that these changes may serve as a marker of biological activity. EXPERIMENTAL
      DESIGN: The effect of angiogenesis inhibitors on CECs was evaluated by flow
      cytometry after vascular endothelial growth factor (VEGF)-induced mobilization
      and in mice bearing Lewis lung carcinoma (LLC). Tumor angiogenesis was evaluated
      in parallel by immunohistochemistry. RESULTS: In nontumor-bearing mice, VEGF
      administration increased both mature CECs and CEPs. This increase was inhibited
      by the VEGF receptor 2 inhibitor ZD6474 as well as the VEGF inhibitor-soluble Flt
      1. ZD6474 had no significant effect on CECs in the absence of exogenous VEGF
      stimulation. In contrast, LLC-bearing mice had an increase in mature CECs but not
      CEPs after 3 days of treatment with ZD6474. The increase in mature CECs was dose
      dependent, accompanied by a decrease in tumor microvessel density, and preceded
      reduction in tumor volume. Treatment of LLC-bearing mice with the vascular
      targeting agent ZD6126 also increased mature CECs. CONCLUSIONS: VEGF inhibitors
      can have differential effects on mature CECs and CEPs, and agents inhibiting
      tumor angiogenesis may cause a concomitant increase in mature CECs. This increase
      occurs in tumor-bearing but not in nontumor-bearing mice, suggesting that tumor
      endothelium is a potential source of mature CECs. Therefore, assessing both
      mature CECs and CEPs may provide insights into the mechanism of antiangiogenic
      agents and serve as an early surrogate marker of biological activity.

PMID- 15867255
TI  - Flavopiridol sensitivity of cancer cells isolated from ascites and pleural
      fluids.
AB  - PURPOSE: We examined the efficacy of flavopiridol, a cyclin-dependent kinase
      inhibitor that is undergoing clinical trials, on primary cancer cells isolated
      from the ascites or pleural fluids of patients with metastatic cancers.
      EXPERIMENTAL DESIGN: Metastasized cancer cells were isolated from the pleural
      fluids (n = 20) or ascites (n = 15) of patients, most of whom were refractory to
      chemotherapy. These primary cancer cells were used within 2 weeks of isolation
      without selecting for proliferative capacities. The 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide viability assay was used to characterize the
      response of these cancer cells to commonly used chemotherapeutic agents, and
      their response to flavopiridol was compared with rapidly dividing cultured cell
      lines. RESULTS: The primary cancer cells displayed phenotypes that were different
      from established cell lines; they had very low replication rates, dividing every
      1 to 2 weeks, and underwent replicative senescence within five passages. These
      primary tumor cells retained their resistance to chemotherapeutic drugs exhibited
      by the respective patients but did not show cross-resistance to other agents.
      However, these cancer cells showed sensitivity to flavopiridol with an average
      LD50 of 50 nmol/L (range, 21.5-69 nmol/L), similar to the LD50 in established
      cell lines. Because senescent cells also showed similar sensitivity to
      flavopiridol, it suggests that the mechanism of action is not dependent on the
      activity of cyclin-dependent kinases that regulate the progression of the cell
      cycle. CONCLUSION: Using cancer cells isolated from the ascites or pleural
      fluids, this study shows the potential of flavopiridol against cancer cells that
      have developed resistance to conventional chemotherapeutic agents.

PMID- 15867256
TI  - Antiangiogenic properties of gold nanoparticles.
AB  - Here, we report an intrinsic property of gold nanoparticles (nanogold): they can
      interact selectively with heparin-binding glycoproteins and inhibit their
      activity. Gold nanoparticles specifically bound vascular permeability
      factor/vascular endothelial growth factor (VPF/VEGF)-165 and basic fibroblast
      growth factor, two endothelial cell mitogens and mediators of angiogenesis
      resulting in inhibition of endothelial/fibroblast cell proliferation in vitro and
      VEGF-induced permeability as well as angiogenesis in vivo. In contrast, nanogold
      did not inhibit VEGF-121 or epidermal growth factor, two non-heparin-binding
      growth factors, mediated cell proliferation. Gold nanoparticles significantly
      inhibited VEGF receptor-2 phosphorylation, intracellular calcium release, and
      migration and RhoA activation in vitro. These results report for the first time a
      novel property of gold nanoparticles to bind heparin-binding proteins and thereby
      inhibit their subsequent signaling events.

PMID- 15867257
TI  - Epigenetic modulation of retinoic acid receptor beta2 by the histone deacetylase
      inhibitor MS-275 in human renal cell carcinoma.
AB  - PURPOSE: Histone deacetylase (HDAC) inhibitors have been shown to reverse
      epigenetic repression of certain genes, including retinoic acid receptor beta2
      (RARbeta2). In this study, we examined whether RARbeta2 expression is repressed
      in human renal cell carcinoma (RCC) and whether the HDAC inhibitor MS-275 may
      revert its epigenetic repression. EXPERIMENTAL DESIGN: Six human tumor RCC cell
      lines were analyzed for RARbeta2 gene expression and for methylation and
      acetylation status at the promoter level. Modulation of RARbeta2 expression and
      correlation with antitumor activity by combination of MS-275 with 13-cis-retinoic
      acid (CRA) was assessed in a RARbeta2-negative RCC cell line. RESULTS: RARbeta2
      expression was either strongly present, weakly expressed, or absent in the RCC
      cell lines analyzed. Methylation-specific PCR indicated that the RARbeta2
      promoter was partially methylated in three of the cell lines. CRA treatment did
      not inhibit clonogenic growth in the RARbeta2-negative cell line RCC1.18, whereas
      MS-275 induced a dose-dependent inhibitory effect. A greater inhibitory effect
      was observed with combination treatment (MS-275 + CRA). Treatment with MS-275 was
      associated with histone acetylation at the promoter level and synergistic gene
      reexpression of RARbeta2 in combination with CRA. RARbeta2 reexpression was
      associated with synergistic induction of the retinoid-responsive gene HOXA5. In
      vivo, single-agent CRA treatment showed no significant effect, whereas MS-275 and
      the combination induced a regression of RCC1.18 tumor xenografts. Discontinuation
      of treatment produced tumor recurrence in MS-275-treated mice, whereas animals
      treated with the combination remained tumor free. CONCLUSION: The HDAC inhibitor
      MS-275 seems to revert retinoid resistance due to epigenetic silencing of
      RARbeta2 in a human RCC model and has greater antitumor activity in combination
      with CRA compared with single agents. Thus, the combination of HDAC inhibitors
      and retinoids may represent a novel therapeutic approach in patients with RCC.

PMID- 15867258
TI  - Noninvasive monitoring of murine tumor blood flow during and after photodynamic
      therapy provides early assessment of therapeutic efficacy.
AB  - PURPOSE: To monitor tumor blood flow noninvasively during photodynamic therapy
      (PDT) and to correlate flow responses with therapeutic efficacy. EXPERIMENTAL
      DESIGN: Diffuse correlation spectroscopy (DCS) was used to measure blood flow
      continuously in radiation-induced fibrosarcoma murine tumors during Photofrin (5
      mg/kg)/PDT (75 mW/cm2, 135 J/cm2). Relative blood flow (rBF; i.e., normalized to
      preillumination values) was compared with tumor perfusion as determined by power
      Doppler ultrasound and was correlated with treatment durability, defined as the
      time of tumor growth to a volume of 400 mm3. Broadband diffuse reflectance
      spectroscopy concurrently quantified tumor hemoglobin oxygen saturation (SO2).
      RESULTS: DCS and power Doppler ultrasound measured similar flow decreases in
      animals treated with identical protocols. DCS measurement of rBF during PDT
      revealed a series of PDT-induced peaks and declines dominated by an initial steep
      increase (average +/- SE: 168.1 +/- 39.5%) and subsequent decrease (59.2 +/-
      29.1%). The duration (interval time; range, 2.2-15.6 minutes) and slope (flow
      reduction rate; range, 4.4 -45.8% minute(-1)) of the decrease correlated
      significantly (P = 0.0001 and 0.0002, r2= 0.79 and 0.67, respectively) with
      treatment durability. A positive, significant (P = 0.016, r2= 0.50) association
      between interval time and time-to-400 mm3 was also detected in animals with
      depressed pre-PDT blood flow due to hydralazine administration. At 3 hours after
      PDT, rBF and SO2 were predictive (P < or = 0.015) of treatment durability.
      CONCLUSION: These data suggest a role for DCS in real-time monitoring of PDT
      vascular response as an indicator of treatment efficacy.

PMID- 15867259
TI  - Reduction of intracellular pH as a strategy to enhance the pH-dependent cytotoxic
      effects of melphalan for human breast cancer cells.
AB  - The microenvironment within solid tumors is slightly acidic, and manipulation of
      this extracellular acidity to cause intracellular acidification might be used to
      increase selective antitumor effects of some anticancer drugs. Potential
      mechanisms include inhibition of repair of DNA damage and inhibition of
      repopulation of tumor cells between successive courses of chemotherapy. Here, we
      evaluate the influence of extracellular pH (pHe) and of two agents that lead to
      intracellular acidification (cariporide and S3705) on toxicity of melphalan for
      two human breast cancer cell lines (MDA-MB231 and MCF7). Both the total number
      and number of colony-forming cells were evaluated during and after three
      sequential weekly drug treatments. Our results indicate the following: (a) Slow
      or absent repopulation after the first course of treatment that is influenced
      minimally by pHe. (b) Rapid repopulation after the second course of treatment
      that may be inhibited at low pHe. (c) Effects of low pHe following treatment with
      melphalan to increase cell kill. (d) Small effects of incubation in cariporide
      and S3705 at low pHe to increase the net cell kill after treatment with
      melphalan. Although these results add to evidence that manipulation of
      intracellular pH within the acidic environment of solid tumors can influence the
      effects of chemotherapy, they are too small and inconsistent to warrant clinical
      evaluation.

PMID- 15867260
TI  - Retinoic acid and the histone deacetylase inhibitor trichostatin a inhibit the
      proliferation of human renal cell carcinoma in a xenograft tumor model.
AB  - PURPOSE: Therapy for advanced renal cell carcinoma (RCC) is ineffective in the
      majority of patients. We have previously reported that retinoid-induced up
      regulation of retinoic acid receptor beta (RARbeta) correlated with antitumor
      effects in RCCs. Recent studies show that there is a reduction in the level of
      RARbeta2 expression in cancer cells due in part to histone hypoacetylation.
      Therefore, we tested whether combining histone deacetylase inhibitors with
      retinoic acid (RA) would restore RARbeta2 receptor expression, leading to
      increased growth inhibition in RCC cells. EXPERIMENTAL DESIGN: Cell
      proliferation, Western blot, and reverse transcription-PCR analyses of two RA
      resistant RCC cell lines, SK-RC-39 and SK-RC-45, were assessed in the presence of
      all-trans retinoic acid (ATRA), trichostatin A (TSA), or the combination of ATRA
      and TSA. Analysis of apoptosis was also done on SK-RC-39 cells treated with these
      combinations. Additionally, a xenograft tumor model (SK-RC-39) was used in this
      study to investigate the efficacy of a liposome-encapsulated, i.v. form of ATRA
      (ATRA-IV) plus TSA combination therapy. RESULTS: Enhanced inhibition of the
      proliferation of RCC cell lines and of tumor growth in a xenograft model was
      observed with the combination of ATRA plus TSA. Reactivation of RARbeta2 mRNA
      expression was observed in SK-RC-39 and SK-RC-45 cells treated with TSA alone or
      TSA in combination with ATRA. A partial G0-G1 arrest and increased apoptosis were
      observed with SK-RC-39 cells on treatment with ATRA and TSA. CONCLUSIONS: The
      combination of ATRA and the histone deacetylase inhibitor TSA elicits an additive
      inhibition of cell proliferation in RCC cell lines. These results indicate that
      ATRA and histone deacetylase inhibitor therapies should be explored for the
      treatment of advanced RCC.

PMID- 15867261
TI  - Anti-CD19-targeted liposomal doxorubicin improves the therapeutic efficacy in
      murine B-cell lymphoma and ameliorates the toxicity of liposomes with varying
      drug release rates.
AB  - Some formulations of liposomal doxorubicin with intermediate rates of drug
      release have shown increased levels of toxicity in mice. Because antibody
      mediated targeting of liposomal drugs influences the pharmacokinetics, mechanism
      of uptake, and selectivity of the associated drugs, we hypothesized that anti
      CD19-mediated targeting of liposomal doxorubicin might moderate the toxicity of
      the problem formulations. Phosphatidylcholine/cholesterol liposomal formulations
      of doxorubicin having faster, intermediate, and slower drug release rates were
      prepared by altering the fatty acyl chain length or degree of saturation of the
      phosphatidylcholine component. Pharmacokinetic and biodistribution studies and in
      vivo drug release rates were determined in mice using liposomes dual labeled with
      [3H]cholesteryl hexadecylether and [14C]doxorubicin. Therapeutic studies were
      done in xenograft models of human B lymphoma (Namalwa cells). The rate of
      clearance of the liposomal lipid was similar for all formulations (average t1/2,
      18 hours), but the rate of clearance of doxorubicin was dependent on the release
      rate of the formulation (t1/2, 2-315 hours). Liposomes with the slowest drug
      release rates showed no toxicity and exhibited therapeutic activity that was
      superior to the other formulations when targeted with anti-CD19; liposomes with
      the most rapid drug release rates also showed no toxicity but showed little
      therapeutic effect even when targeted. Liposomes with intermediate drug release
      rates exhibited varying degrees of toxicity. The toxicities could be reduced and
      even overcome by targeting with anti-CD19 antibodies. For these formulations,
      therapeutic effects were intermediate between those found for liposomes with the
      fastest and slowest drug release rates.

PMID- 15867262
TI  - Combined liposome-mediated cytosine deaminase gene therapy with radiation in
      killing rectal cancer cells and xenografts in athymic mice.
AB  - PURPOSE: The aim of this study was to assess the antitumor efficacy of
      combination of cytosine deaminase (CD) suicide gene therapy with radiation and to
      grope for new therapeutic strategy for local recurrent rectal cancer.
      EXPERIMENTAL DESIGN: HR-8348 cell line of human rectal cancer was used to assess
      efficiency of transfection with plasmid pEGFP-N1 and PXJ41-CD. The cells were
      exposed to radiation followed by liposome-mediated transfection. Cell inhibition
      assay was done with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      method. Antitumor efficacy of combined liposome-mediated CD suicide gene therapy
      with radiation was determined by treatment of nude mice bearing HR-8348 cancer
      cell xenograft. RESULTS: The efficiency of liposome-mediated CD gene transfection
      can be improved by radiation. With radiation at 2, 4, 6, and 8 Gy, the efficiency
      of liposome-mediated transfection increased from 21.3% to 62.2%, 78.0%, 83.2%,
      and 87.8%, respectively. CD expression was enhanced as well. Cancer cell
      inhibition experiment showed that combined liposome-mediated CD gene therapy with
      radiation had much stronger antitumor effect. With HR-8348 tumor xenograft model,
      suppression of tumor xenograft was observed. Compared with control group, tumor
      volume was inhibited by 81.5%, 48.5%, and 37.4%, respectively, in the combined
      CD/5-fluorocytosine with radiation group, CD/5-fluorocytosine group, and
      radiation group and the wet weight of tumor was decreased by 80%, 41.7%, and
      37.7%, respectively. CONCLUSION: These findings suggested that combination of
      liposome-mediated CD gene therapy with radiation is a safer and efficient
      anticancer method. Its therapeutic efficacy may meet clinical treatment on local
      recurrent rectal cancer.

PMID- 15867263
TI  - Autocrine metabolism of vitamin D in normal and malignant breast tissue.
AB  - PURPOSE: Vitamin D seems to exert a protective effect against common cancers,
      although this does not correlate with circulating levels of active 1,25
      dihydroxyvitamin D3 [1,25(OH)2D3], indicating a more localized activation of
      vitamin D. The aim of this study was to investigate the significance of this in
      breast cancer. EXPERIMENTAL DESIGN: Quantitative reverse transcription-PCR
      analysis of mRNA expression was carried out for the vitamin D-activating enzyme
      1alpha-hydroxylase, the catabolic enzyme 24-hydroxylase, and the vitamin D
      receptor in 41 tumors and paired nonneoplastic tissue as well as breast cancer
      cell lines. Immunohistochemistry was used to assess 1alpha-hydroxylase protein
      expression, and enzyme assays were used to quantify vitamin D metabolism.
      RESULTS: Expression of mRNA for 1alpha-hydroxylase (27-fold; P < 5 x 10(-11)),
      vitamin D receptor (7-fold; P < 1.5 x 10(-8)), and 24-hydroxylase (4-fold; P <
      0.02) was higher in breast tumors. 1alpha-Hydroxylase enzyme activity was also
      higher in tumors (44.3 +/- 11.4 versus 12.4 +/- 4.8 fmol/h/mg protein in
      nonneoplastic tissue; P < 0.05). However, production of inactive 1,24,25
      trihydroxyvitamin D3 was also significantly higher in tumors (84.8 +/- 11.7
      versus 33.6 +/- 8.5 fmol/h/mg protein; P < 0.01). Antisense inhibition of 24
      hydroxylase in vitro increased antiproliferative responses to 1,25(OH)2D3.
      CONCLUSION: These data indicate that the vitamin D-activating enzyme 1alpha
      hydroxylase is up-regulated in breast tumors. However, dysregulated expression of
      24-hydroxylase seems to abrogate the effects of local 1,25(OH)2D3 production in
      tumors by catalyzing catabolism to less active vitamin D metabolites. The enzymes
      involved in autocrine metabolism of vitamin D in breast tissue may therefore
      provide important targets for both the prevention and treatment of breast cancer.

PMID- 15867264
TI  - Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and
      pancreatic intraepithelial neoplasia.
AB  - PURPOSE: Despite significant progress in understanding the molecular pathology of
      pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia
      (PanIN), there remain no molecules with proven clinical utility as prognostic or
      therapeutic markers. Here, we used oligonucleotide microarrays to interrogate
      mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel
      molecular pathways dysregulated in the development and progression of pancreatic
      cancer. EXPERIMENTAL DESIGN: RNA was hybridized to Affymetrix Genechip HG-U133
      oligonucleotide microarrays. A relational database integrating data from publicly
      available resources was created to identify candidate genes potentially relevant
      to pancreatic cancer. The protein expression of one candidate, homeobox B2
      (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry.
      RESULTS: We identified aberrant expression of several components of the retinoic
      acid (RA) signaling pathway (RARalpha, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, and
      HOXB2), many of which are known to be aberrantly expressed in pancreatic cancer
      and PanIN. HOXB2, a downstream target of RA, was up-regulated 6.7-fold in
      pancreatic cancer compared with normal pancreas. Immunohistochemistry revealed
      ectopic expression of HOXB2 in 15% of early PanIN lesions and 48 of 128 (38%)
      pancreatic cancer specimens. Expression of HOXB2 was associated with
      nonresectable tumors and was an independent predictor of poor survival in
      resected tumors. CONCLUSIONS: We identified aberrant expression of RA signaling
      components in pancreatic cancer, including HOXB2, which was expressed in a
      proportion of PanIN lesions. Ectopic expression of HOXB2 was associated with a
      poor prognosis for all patients with pancreatic cancer and was an independent
      predictor of survival in patients who underwent resection.

PMID- 15867265
TI  - Growth and molecular interactions between tamoxifen and trastuzumab.

PMID- 15867266
TI  - Nutritional, dietary and postprandial oxidative stress.
AB  - Nutritional, or dietary oxidative stress denotes a disturbance of the redox state
      resulting from excess oxidative load or from inadequate nutrient supply favoring
      prooxidant reactions. Low intake or impaired availability of dietary antioxidants
      including vitamins E and C, carotenoids, polyphenols, and other micronutrients
      (e.g., selenium) weakens the antioxidant network. Postprandial oxidative stress,
      as a subform of nutritional oxidative stress, ensues from sustained postprandial
      hyperlipidemia and/or hyperglycemia and is associated with a higher risk for
      atherosclerosis, diabetes, and obesity. In Western societies, a significant part
      of the day is spent in the postprandial state. Unsaturated fatty acids
      incorporated into LDL and oxidized LDL are an atherogenic factor. Lipid
      hydroperoxides present in the diet are absorbed, contributing to the prooxidant
      load. In hyperlipidemic and hyperglycemic subjects, endothelium-dependent
      vasodilation is impaired in the postprandial state, making postprandial oxidative
      stress an important factor modulating cardiovascular risk. Postprandial oxidative
      stress is attenuated when dietary antioxidants are supplied together with a meal
      rich in oxidized or oxidizable lipids. Ingestion of dietary polyphenols, e.g.,
      from wine, cocoa, or tea, improves endothelial dysfunction and lowers the
      susceptibility of LDL lipids to oxidation. Polyphenols affect endothelial
      function not solely as antioxidants but also as modulatory signaling molecules.

PMID- 15867267
TI  - Marginal maternal biotin deficiency in CD-1 mice reduces fetal mass of biotin
      dependent carboxylases.
AB  - Marginal maternal biotin deficiency reduces hepatic activity of biotin-dependent
      carboxylases and causes high rates of fetal birth defects in mice. We tested the
      hypothesis that the decreased carboxylase activity observed in deficient dams and
      their offspring is mediated by decreased abundance of biotinylated carboxylases,
      decreased expression of their mRNAs, or both. During gestation, CD-1 mice were
      fed a diet that induced biotin deficiency or a biotin-sufficient diet. On
      gestational d 17, gravid uteri were removed, and each live fetus was examined
      grossly for defects. The expected high incidence of cleft palate (83%) in
      offspring was observed. In maternal and fetal liver, acetyl-CoA carboxylase,
      pyruvate carboxylase, propionyl-CoA carboxylase, and beta-methylcrotonyl-CoA
      carboxylase abundances were determined by Western blotting; the content of mRNAs
      for most of these enzymes and holocarboxylase synthetase was determined by real
      time RT-PCR. Biotin deficiency significantly reduced the abundance of the
      carboxylases in maternal and fetal liver; neither the content of mRNAs for the
      carboxylases nor holocarboxylase synthetase changed. This study provides evidence
      that the decrease in carboxylase activities is attributable to a decrease in the
      abundance of biotinylated carboxylases; further, this effect is more severe in
      fetuses than dams.

PMID- 15867268
TI  - Riboflavin deficiency impairs oxidative folding and secretion of apolipoprotein B
      100 in HepG2 cells, triggering stress response systems.
AB  - Secretory proteins such as apolipoprotein B-100 (apoB) undergo oxidative folding
      (formation of disulfide bonds) in the endoplasmic reticulum (ER) before
      secretion. Oxidative folding depends on flavoproteins in eukaryotes. Here, human
      liver (HepG2) cells were used to model effects of riboflavin concentrations in
      culture media on folding and secretion of apoB. Cells were cultured in media
      containing 3.1, 12.6, and 300 nmol/L of riboflavin, representing moderately
      deficient, physiological, and pharmacological plasma concentrations in humans,
      respectively. When cells were cultured in riboflavin-deficient medium, secretion
      of apoB decreased by >80% compared with controls cultured in physiological
      medium. The nuclear translocation of the transcription factor ATF-6 increased by
      >180% in riboflavin-deficient cells compared with physiological controls; this is
      consistent with ER stress. Nuclear translocation of ATF-6 was associated with
      activation of the unfolded protein response. Expression of stress-response genes
      coding for ubiquitin-activating enzyme 1, growth arrest and DNA damage inducible
      gene, and glucose regulated protein of 78 kDa was greater in riboflavin-deficient
      cells compared with other treatment groups. Finally, phosphorylation of the
      eukaryotic initiation factor (eukaryotic initiation factor 2alpha) increased in
      riboflavin-deficient cells, consistent with decreased translational activity. We
      conclude 1) that riboflavin deficiency causes ER stress and activation of
      unfolded protein response in HepG2 cells, and 2) that riboflavin deficiency
      decreases protein secretion in HepG2 cells. Decreased secretion of apoB in
      riboflavin-deficient cells might interfere with lipid homeostasis in vivo.

PMID- 15867269
TI  - Dietary (n-3) polyunsaturated fatty acids inhibit HER-2/neu-induced breast cancer
      in mice independently of the PPARgamma ligand rosiglitazone.
AB  - Overexpression of human epidermal growth factor receptor 2 (HER-2/neu)
      characterizes a molecular subtype of breast cancer associated with poor clinical
      outcome. Preventive strategies for HER-2/neu-positive breast cancer, which is
      often estrogen and progesterone receptor negative, remain undefined. Activators
      of peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear
      hormone receptor also expressed in breast cancer, hold potential as cancer
      prevention agents. PPARgamma ligands include specific fatty acids and synthetic
      compounds, such as the thiazolidinediones, which appear to inhibit cell
      proliferation and tumorigenesis. We hypothesized that a thiazolidinedione,
      rosiglitazone, may serve as a chemopreventive agent for HER-2/neu-associated
      mammary carcinogenesis, but that efficacy may be influenced by dietary fat
      content. We studied the effects of diets enriched with corn or fish oil (25% of
      energy) with and without rosiglitazone (12 g/kg) in a 2 x 2 factorial design on
      mammary tumorigenesis in murine mammary tumor virus (MMTV)-HER-2/neu transgenic
      mice. Despite in vitro evidence of antiproliferative effects in an MMTV-HER-2/neu
      tumor cell line, rosiglitazone did not affect mammary carcinogenesis in vivo.
      Interestingly, fish oil-based diets markedly suppressed breast tumor incidence
      (57% of mice vs. 87% of corn oil-fed mice, P = 0.0001) as well as tumor
      multiplicity (P = 0.001) and mammary gland dysplasia (P = 0.001). These findings
      demonstrate a potent preventive effect of (n-3) PUFA on HER-2/neu-mediated
      mammary carcinogenesis, without interaction with a synthetic PPARgamma activator.
      Further studies focusing on the mechanisms by which (n-3) fatty acids suppress
      HER-2/neu signaling pathways involved in the pathogenesis of breast cancer are
      warranted.

PMID- 15867270
TI  - Dietary genistein improves survival and reduces expression of osteopontin in the
      prostate of transgenic mice with prostatic adenocarcinoma (TRAMP).
AB  - Studies in vitro suggest that osteopontin (OPN), an extracellular matrix protein
      secreted by macrophages infiltrating prostate tumors, and by tumor cells, may
      have a role in the transition from clinically insignificant tumors to metastatic
      prostate cancer (PC). Latent PC occurs at equal rates in Western and Asian men,
      but the incidence of advanced PC is many-fold higher in Western men. Our earlier
      studies in TRAnsgenic Mouse Prostate adenocarcinoma (TRAMP) mice showed that
      genistein, an isoflavone found in soybeans, lowered the incidence of advanced PC.
      This suggested that lower intake of dietary soy may be one possible cause for
      higher incidence of advanced PC in Western men. The objective of the present
      study was to test the hypothesis that genistein may exert its preventive effect
      by inhibiting OPN expression. From 5 to 28 wk of age, 80, 68, and 30 TRAMP mice
      were fed AIN-76A diet containing 0, 250, or 500 mg genistein/kg body weight,
      respectively. Organ weights were measured. The steady-state level of OPN mRNA was
      evaluated by RT-PCR in a longitudinal study in 74 TRAMP and 32 nontransgenic
      litter mates (NTM). Administration of 250 and 500 mg genistein/kg AIN-76A
      improved survival (P = 0.008 and P = 0.005, respectively) and reduced mean weight
      of prostates with poorly differentiated cancer (PD) (P < 0.001), as well as the
      mean weight of periaortic lymph nodes (LN), although the latter was not
      significant. OPN was upregulated 10-fold in PD compared with prostates with a
      lower pathological score from TRAMP or NTM of any age (P = 0.003). OPN mRNA
      levels in the dorsolateral prostate and metastasis to LN were significantly
      correlated (r = 0.643; P = 0.00006). Genistein had a dose-dependent, significant
      inhibitory effect on OPN transcript levels in prostates displaying advanced
      prostate cancer (PD; score 6; P = 0.05). Studies are consistent with the
      possibility that dietary genistein may delay the progression from benign to
      malignant tumors by inhibiting OPN expression.

PMID- 15867271
TI  - A synbiotic combination of resistant starch and Bifidobacterium lactis
      facilitates apoptotic deletion of carcinogen-damaged cells in rat colon.
AB  - Recent reports suggest that combinations of prebiotics and probiotics may be
      protective against colorectal cancer. We examined in rats the effects of
      probiotic bacteria, resistant starch (RS), and their interaction on luminal and
      epithelial events of relevance to the development of colorectal cancer.
      Lyophilized cultures (1 x 10(10) cfu/g) of Lactobacillus acidophilus and/or
      Bifidobacterium lactis were added at a concentration of 1% by weight to a
      semipurified diet containing either low-RS (no supplemented RS) or moderate-RS
      (10% Hi-maize) and fed to male Sprague-Dawley rats for 4 wk. Experimental end
      points included cecal bacterial enumeration, fecal and cecal pH, SCFA levels,
      cell proliferation, and the acute apoptotic response to a genotoxic carcinogen
      (AARGC; measured 6 h after a single azoxymethane injection). A significant
      interaction between dietary RS and supplemental bacteria was observed for the
      AARGC in the colon and fecal pH (P < 0.01). Rats fed the moderate-RS diet in
      combination with B. lactis had a significantly greater AARGC in the colon than
      those fed that diet without B. lactis. Fecal pH was elevated in the moderate-RS
      fed rats supplemented with bacteria. The moderate-RS diet increased cell
      proliferation and crypt column height (P < 0.001) compared with the low-RS diet.
      SCFA levels and numbers of bifidobacteria and lactobacilli species were also
      increased (P < 0.001) by the moderate-RS diet, whereas pH levels and total
      coliforms were lowered (P < 0.001). The synbiotic combination of RS and B. lactis
      significantly facilitated the apoptotic response to a genotoxic carcinogen in the
      distal colon of rats. It appears likely that ingested RS acts as a metabolic
      substrate, thus creating the right conditions for B. lactis to exert its
      proapoptotic action. Because the synbiotic combination of these agents
      facilitates the apoptotic response to DNA damage by a cancer initiator in the
      colon of rats, it warrants further study for its capacity to protect against
      colorectal cancer.

PMID- 15867272
TI  - Zinc deficiency is associated with increased brain zinc import and LIV-1
      expression and decreased ZnT-1 expression in neonatal rats.
AB  - Zinc (Zn) deficiency has been associated with adverse behavioral outcomes in
      infants and children. However, Zn deficiency does not affect brain Zn
      concentration, suggesting that brain Zn homeostasis is tightly regulated. The
      recent identification of Zn-specific transport proteins allowed us to examine
      effects of low Zn intake on tissue Zn level, brain Zn uptake, and zinc
      transporter expression and localization in neonatal rat brain. Female rats were
      fed diets differing only in Zn content [7, moderately zinc deficient (ZD); 10,
      marginally zinc deficient (MZD); or 25 mg Zn/kg, control] and pups were killed on
      postnatal d 11. Plasma and brain Zn concentrations were measured, brain Zn uptake
      was assessed using (65)Zn, brain metallothionein-I and -III; LIV-1, zinc
      transporter ZnT-1, and ZnT-3 expression was measured by semiquantitative RT-PCR.
      LIV-1 localization in the brain was determined by immunohistochemistry; brain and
      hippocampi LIV-1 and ZnT-1 protein expressions were measured by Western blotting.
      Plasma Zn concentration was lower in MZD and ZD pups, whereas brain Zn
      concentration was not affected. Brain Zn uptake was higher in MZD and ZD rats
      compared with controls. Metallothionein-I and ZnT-1 expressions were lower and
      LIV-1 expression was higher in the whole brain of MZD and ZD pups.
      Metallothionein-III and ZnT-3 mRNA expressions were not affected. LIV-1 was
      localized to the plasma membrane of many brain cell types, including hippocampal
      pyramidal neurons and the apical membrane of the choroid plexus. Our results
      indicate that Zn deficiency results in alterations in Zn transporter expression,
      which facilitates increased brain Zn uptake and results in the conservation of
      brain Zn during Zn deficiency.

PMID- 15867273
TI  - Dietary docosahexaenoic acid [22: 6(n-3)] as a phospholipid or a triglyceride
      enhances the potassium chloride-evoked release of acetylcholine in rat
      hippocampus.
AB  - We demonstrated previously that a dietary-induced depletion of docosahexaenoic
      acid (DHA) in cerebral phospholipids increases the spontaneous release of
      acetylcholine (Ach) in the rat hippocampus and reduces its potassium chloride
      evoked-release. In the present study, we investigated the effects in rats of DHA
      enriched diets supplied by egg phospholipids (E-PL) or tuna oil (TO) on the PUFA
      in hippocampus membranes and on the synaptic release of Ach. Control rats were
      fed 3 g/kg of the DHA precursor, alpha-linolenic acid (LNA). Chronically (n-3)
      PUFA-deficient females were fed, starting 2 wk before mating, the deficient diet,
      a control diet, or a purified diet supplying 1, 2, or 3 g DHA/kg diet as E-PL or
      TO. Experiments were performed on the adult male progeny fed the same diet as
      their dams throughout life. The form of dietary DHA (TO or E-PL) did not
      influence its incorporation into the hippocampus. The 1 g DHA/kg diets allowed
      maximal incorporation into phosphatidylethanolamine (PE), but 2 g DHA/kg diet was
      needed for phosphatidylcholine (PC). A minimum of 2 g DHA/kg was needed to
      decrease the basal Ach release and to enhance the stimulated release to that of
      the control; the Ach release of the 1 g/kg DHA-groups did not differ from that of
      the deficient group. This suggests that >1 g DHA/kg diet is needed to ensure PUFA
      incorporation into PE and PC, and basal and stimulated Ach release in the rat
      hippocampus equivalent to the control group fed only LNA. PUFA incorporation into
      the hippocampus depends mainly on the PUFA concentration of the diet, not on the
      form of dietary DHA.

PMID- 15867274
TI  - Human cortical specialization for food: a functional magnetic resonance imaging
      investigation.
AB  - Although specialized cortical pathways that process specific sensory stimuli
      and/or execute cognitive functions have been identified, the neuro-specificity
      for food-related stimuli has not been clearly demonstrated. We employed
      functional magnetic resonance imaging (fMRI) to compare neural systems associated
      with the appreciation of foods and nonfoods. Healthy, normal weight, right-handed
      men and women (n = 12; age 29.8 +/- 1.8 y, BMI 21.8 +/- 0.8 kg/m(2)) were imaged
      by fMRI while fasting. Real food and nonfood items were presented to subjects
      both visually and tactilely, during scanning. Subjects were instructed to pay
      attention to the items. A randomized 2 x 2 block design consisted of 4
      conditions: visual food, visual nonfood, tactile food, and tactile nonfood. Brain
      regions that were significantly activated to a greater extent during the
      presentation of foods compared with nonfood items included the anterior
      cingulate, superior temporal gyrus, parahippocampal gyrus, hippocampus, and the
      insula. These findings support the claim that the presence of food (either seen
      or felt) elicits a unique cortical response that is differentiated from nonfood
      items. This neural substrate specialized for processing of foods informs models
      of food-related behavior.

PMID- 15867275
TI  - Lead exposure and (n-3) fatty acid deficiency during rat neonatal development
      affect subsequent spatial task performance and olfactory discrimination.
AB  - Docosahexaenoic acid [22:6(n-3), DHA] is important for optimal infant central
      nervous system development, and lead (Pb) exposure during development can produce
      neurological deficits. Long-Evans strain rats were fed either an (n-3) deficient
      [(n-3) Def] diet to produce brain DHA deficiency, or an adequate [(n-3) Adq] diet
      through 2 generations. At the birth of the 2nd generation, the dams were
      subdivided into 4 groups and supplied drinking water containing either 5.27
      mmol/L (Pb) or sodium (Na) acetate until weaning. Rats were killed at 3 wk
      (weaning) and 11 wk (maturity) for brain Pb and fatty acid analysis. Spatial task
      and olfactory-cued behavioral assessments were initiated at 9 wk. Rats in the (n
      3) Def group had a 79% lower concentration of brain DHA compared with the (n-3)
      Adq group with no effect of Pb exposure. At weaning, Pb concentrations were 7.17
      +/- 0.47 nmol Pb/g of brain (wet weight) in the (n-3) Adq-Pb group and 6.49 +/-
      0.63 nmol Pb/g of brain (wet weight) in the (n-3) Def-Pb group. At maturity, the
      brains contained 1.30 +/- 0.22 and 1.07 +/- 0.12 nmol Pb/g (wet weight),
      respectively. In behavioral testing, significant effects of both Pb and DHA
      deficiency were observed in the Morris water maze probe trial and in 2-odor
      olfactory discrimination acquisition and olfactory-based reversal learning tasks.
      Both lactational Pb exposure and (n-3) fatty acid deficiency led to behavioral
      deficits with additive effects observed only in the acquisition of 2-odor
      discriminations.

PMID- 15867276
TI  - Lead exposure and (n-3) fatty acid deficiency during rat neonatal development
      alter liver, plasma, and brain polyunsaturated fatty acid composition.
AB  - Lead (Pb) exposure has been reported to increase arachidonic (AA) and
      docosahexaenoic (DHA) acids. To determine whether Pb effects on fatty acid
      composition are influenced by dietary (n-3) fatty acid restriction, weanling
      female rats were fed either an (n-3)-adequate or -deficient diet to maturity and
      mated. At parturition, dams in each group were subdivided to receive either 0.2%
      Pb or Na-acetate in their drinking water during lactation only. Pups were
      analyzed for fatty acid content in liver, plasma, and brain at either 3 or 11 wk.
      The (n-3)-deficient diets markedly decreased total (n-3) fatty acids, and
      increased total (n-6) fatty acids including both AA and docosapentaenoic (n-6) in
      each compartment (P < 0.05). The main effects of Pb were in the livers of
      weanling rats where there was a 56% loss in total fatty acid concentration
      concurrent with increased relative percentages of AA and DHA. Thus, because there
      was a greater percentage of liver nonessential fatty acid lost relative to the
      essential fatty acids (EFA), there was no net change in AA concentration. There
      was a diet x Pb interaction for a decrease in liver DHA concentration evident
      only in the (n-3)-adequate group. There were also diet x Pb interactions in
      plasma at 11 wk and in brain at 3 wk. These data are consistent with the
      hypothesis of a Pb-induced increase in fatty acid catabolism, perhaps as a source
      of energy.

PMID- 15867277
TI  - Sulfur amino acid restriction induces the pi class of glutathione S-transferase
      expression in primary rat hepatocytes.
AB  - The regulation of genes by amino acids is attracting increasing attention. In the
      present study, we investigated the restriction of expression of the pi class of
      glutathione S-transferase (GST Yp) by sulfur amino acids. Hepatocytes isolated
      from male Sprague-Dawley rats were cultured with L-15-based medium containing low
      (LSAA; 0.1 mmol/L L-methionine and 0.1 mmol/L L-cysteine) or high (HSAA; 0.5
      mmol/L L-methionine and 0.2 mmol/L L-cysteine) amounts of sulfur amino acids for
      up to 6 d. Cellular protein contents did not differ between LSAA- and HSAA
      treated cells over the entire period. In contrast, glutathione concentrations
      were suppressed by the LSAA medium and on d 6 were only 20% of those of HSAA
      treated cells (P < 0.05). As shown by immunoblot analysis, GST Yp protein levels
      were greater in LSAA-treated cells than in HSAA-treated cells (P < 0.05). The
      induction of GST Yp by L-methionine and L-cysteine restriction was not affected
      by insulin and dexamethasone, but the latter suppressed GST Yp expression (P <
      0.05). LSAA increased GST Yp mRNA levels and GST activity toward ethacrynic acid
      (P < 0.05). GST Yp induction occurred only in cells with a limited supply of L
      methionine; restriction of L-isoleucine, L-leucine, L-lysine, and L-phenylalanine
      had no significant effect. In contrast with the induction of GST Yp, the
      expression of the GST isoforms Ya and Yb was not changed by amino acid
      restriction. In conclusion, hepatic GST Yp gene expression is upregulated by a
      limited availability of sulfur amino acids.

PMID- 15867278
TI  - The methylenetetrahydrofolate reductase 677C->T polymorphism and dietary folate
      restriction affect plasma one-carbon metabolites and red blood cell folate
      concentrations and distribution in women.
AB  - Whether folate status and the methylenetetrahydrofolate reductase (MTHFR) 677C-
      >T polymorphism interact to affect methionine-cycle metabolite concentrations is
      uncertain. We evaluated the effects of dietary folate restriction on relations
      among folate status indices and plasma concentrations of methionine cycle
      metabolites in women with the MTHFR 677 C/C and T/T genotypes. Healthy,
      normohomocysteinemic women (n = 18; 20-30 y old) of adequate B vitamin status,
      and equally divided according to MTHFR 677C-->T genotype (9 C/C and 9 T/T) were
      recruited. Folate status indices and methionine cycle metabolites were measured
      in blood samples collected at baseline and after 7 wk of dietary folate
      restriction (115 microg dietary folate equivalents/d). Significant negative
      correlations between plasma total homocysteine concentrations and total or 5
      methyl folate concentrations (P = 0.041 and 0.023, respectively) in RBCs were
      found only in T/T subjects. Formylated folates were detected in RBCs of T/T
      subjects only, and their abundance was predictive of plasma total homocysteine
      concentration despite no significant alteration by folate restriction. Plasma
      concentrations of S-adenosylmethionine and S-adenosylhomocysteine were not
      significantly affected by dietary folate restriction and the MTHFR 677 T/T
      genotype. In conclusion, plasma total homocysteine concentrations in subjects
      with the MTHFR 677 T/T genotype were inversely related to 5-methyl folate
      concentrations and directly related to formylated folate concentrations in RBCs,
      even though the latter were not significantly affected by moderate folate
      restriction.

PMID- 15867279
TI  - Homocysteine synthesis is elevated but total remethylation is unchanged by the
      methylenetetrahydrofolate reductase 677C->T polymorphism and by dietary folate
      restriction in young women.
AB  - The effects of folate status and the methylenetetrahydrofolate reductase (MTHFR)
      677C-->T polymorphism on the kinetics of homocysteine metabolism are unclear. We
      measured the effects of dietary folate restriction on the kinetics of
      homocysteine remethylation and synthesis in healthy women (20-30 y old) with the
      MTHFR 677 C/C or T/T genotypes (n = 9/genotype) using i.v. primed, constant
      infusions of [(13)C(5)]methionine, [3-(13)C]serine, and [(2)H(3)]leucine before
      and after 7 wk of dietary folate restriction (115 mug dietary folate
      equivalents/d). Dietary folate restriction significantly reduced folate status (
      approximately 65% reduction in serum folate) in both genotypes. Total
      remethylation flux was not affected by dietary folate restriction, the MTHFR 677C
      ->T polymorphism, or their combination. However, the percentage of remethylation
      from serine was reduced approximately 15% (P = 0.031) by folate restriction in
      C/C subjects. Further, homocysteine synthesis rates of T/T subjects and folate
      restricted C/C subjects were twice that of C/C subjects at baseline. In
      conclusion, elevated homocysteine synthesis is a cause of mild
      hyperhomocysteinemia in women with marginal folate status, particularly those
      with the MTHFR 677 T/T genotype.

PMID- 15867280
TI  - Cruciferae interact with the UGT1A1*28 polymorphism to determine serum bilirubin
      levels in humans.
AB  - UDP-glucuronosyltransferase (UGT) 1A1 is a conjugating biotransformation enzyme
      that plays a role in maintaining levels of endogenous compounds (e.g., bilirubin)
      and handling exogenous compounds, including carcinogens. The UGT1A1*28
      polymorphism results in decreased UGT1A1 promoter activity due to 7 thymine
      adenine (TA) repeats instead of the commonly found 6 repeats. Studies indicate
      that foods from the botanical families Cruciferae (e.g., broccoli), Rutaceae
      (citrus), Liliaceae (e.g., onions), and Leguminosae (legumes) may increase UGT
      activity. We investigated, in an observational study, whether foods from these
      botanical groups were associated with increased UGT1A1 activity as indicated by
      serum bilirubin concentrations and whether the effect varied by UGT1A1*28
      genotype, comparing those homozygous for the [TA](7)-repeat allele (7/7) to
      homozygous wild-types (6/6) and heterozygotes (6/7) combined. Healthy volunteers
      completed 3-d food records. Blood samples were drawn for genomic DNA collection
      and bilirubin measures. For total, direct, and indirect bilirubin measures, there
      was no significant association with any botanical group independently. There was
      a significant inverse association between all 3 bilirubin measures and
      interaction of UGT1A1*28 genotype with Cruciferae intake (P < 0.02 for each
      measure); individuals with the 7/7 genotype had reduced bilirubin concentrations
      with increased intake of cruciferous vegetables, whereas individuals with the 6/6
      or 6/7 genotype did not. With regard to UGT1A1-conjugated carcinogens (e.g.,
      heterocyclic amines, polycyclic aromatic hydrocarbons), individuals with
      decreased UGT1A1 activity due to the 7/7 genotype may be at greater risk for
      carcinogenesis, but our results imply that they also may have greater opportunity
      to decrease that risk through dietary intervention.

PMID- 15867281
TI  - Dietary sesamin is converted to enterolactone in humans.
AB  - Sesamin, a major sesame seed lignan, has many biological actions. The specific
      mechanisms for most of these actions as well as the full metabolic pathway of
      sesamin in humans are unclear. Two experiments were carried out to determine
      whether postprandial plasma enterolactone is related to sesamin concentration in
      sesame seeds and whether enterolactone is the major product of the in vitro
      fermentation of sesamin. Four subjects (3 women, 1 man) were given a single dose
      of sesame seeds after they consumed a low-lignan diet for 1 wk. Blood was
      collected at baseline and at time intervals after intake and plasma was analyzed
      for plant and mammalian lignan concentrations. Additionally, pure sesamin
      standard was incubated in vitro with human fecal inoculum to mimic the
      fermentation process in human gut. We calculated individual pharmacokinetic
      variables and found high interindividual variation in the plasma plant lignan
      concentrations. The mammalian lignan appearance rate in plasma shows that sesamin
      is a major precursor of enterolactone in vivo. In the in vitro experiment,
      enterolactone was the major metabolite and 3 intermediates were identified,
      allowing the elucidation of sesamin metabolism in humans. Enterolactone was the
      major metabolite of sesamin both in vivo and in vitro. The abundance of sesamin
      in sesame seeds indicates that they are a major food source of enterolactone
      precursors.

PMID- 15867282
TI  - Noncompetitive plasma biokinetics of deuterium-labeled natural and synthetic
      alpha-tocopherol in healthy men with an apoE4 genotype.
AB  - Previous studies comparing the biokinetics of deuterated natural (RRR) and
      synthetic (all-rac) alpha-tocopherol (vitamin E) used a simultaneous ingestion or
      competitive uptake approach and reported relative bioavailability ratios close to
      2:1, higher than the accepted biopotency ratio of 1.36:1. The aim of the current
      study was to compare the biokinetics of deuterated natural and synthetic vitamin
      E using a noncompetitive uptake model both before and after vitamin E
      supplementation in a distinct population. Healthy men (n = 10) carrying the
      apolipoprotein (apo)E4 genotype completed a randomized crossover study, comprised
      of two 4-wk treatments with 400 mg/d (RRR-alpha-tocopheryl and all-rac-alpha
      tocopheryl acetate) with a 12-wk washout period between treatments. Before and
      after each treatment period, the subjects consumed a capsule containing 150 mg
      deuterated alpha-tocopheryl acetate in either the RRR or all-rac form depending
      on their treatment regimen. Blood was obtained up to 48 h after ingestion, and
      tocopherols analyzed by LC/MS. After deuterated all-rac administration, plasma
      deuterated tocopherol maximum concentrations and area under the concentration vs.
      time curves (AUC) were lower than those following RRR administration. The RRR:all
      rac ratios determined from the deuterated biokinetic profiles (maximum
      concentration; C(max)) and AUCs were 1.35:1 +/- 0.17 and 1.33:1 +/- 0.18,
      respectively. The 4-wk supplementation with either RRR or all-rac significantly
      increased plasma alpha-tocopherol concentrations (P < 0.001), but decreased the
      plasma response to newly absorbed deuterated RRR or all-rac alpha-tocopherol.
      Using a noncompetitive uptake approach, the relative bioavailability of natural
      to synthetic vitamin E in apoE4 males was close to the currently accepted
      biopotency ratio of 1.36:1.

PMID- 15867283
TI  - Interstitial glucose level is a significant predictor of energy intake in free
      living women with healthy body weight.
AB  - The relative contribution of circulating glucose to meal-to-meal variability in
      energy intake is not known. In 8 free-living young (median age 26.5 y) women with
      healthy body weight (median BMI 22.2 kg/m(2)), we measured glucose in the
      interstitial space by an automated monitoring procedure (continuous glucose
      monitoring system, CGMS) for up to 3 consecutive days (mean 706 glucose readings
      per subject). We examined the association between interstitial glucose (which
      lags blood glucose by approximately 10 min), self-reported hunger, satiety,
      desire for a meal, and nutrient intakes. Participants reported consuming a
      typical Western diet (59% carbohydrate, 27% fat, 14% protein). Median
      (interquartile range) interstitial glucose was 5.2 mmol/L (4.7-5.8). Using
      repeated-measures techniques in univariate analyses, desire for a meal (r = 0.45,
      P < 0.0001), hunger (r = 0.37, P = 0.0002), satiety (r = -0.40, P < 0.0001), low
      interstitial absolute mean glucose up to 25 min before eating (r = -0.23, P =
      0.02), and a large decline in glucose between 40 and 5 min before eating (r = 
      0.17, P = 0.08) were all associated with meal energy intake. In multivariate
      regression analyses, desire for a meal (P < 0.0001) and hunger (P = 0.02) were
      the strongest independent contributors to meal energy intake, whereas absolute
      mean glucose measured in the period 15 to 0 min before eating was marginally
      significant (P = 0.08). In conclusion, absolute glucose level is a significant
      predictor of energy intake in nonobese women. However, desire for a meal and
      hunger are quantitatively more important, emphasizing the importance of both
      glucose signals and nonglucose (internal or environmental) factors in within
      subject variability in energy intake. In addition, the CGMS may have utility in
      understanding the role of circulating glucose in energy regulation in free-living
      subjects under a wide range of different nutritional conditions.

PMID- 15867284
TI  - Lipid response to a low-fat diet with or without soy is modified by C-reactive
      protein status in moderately hypercholesterolemic adults.
AB  - Recent evidence suggests that individuals with high concentrations of C-reactive
      protein (CRP), a marker of inflammation, are less responsive to cholesterol
      lowering diets. CRP concentrations are increased by oral estrogen; however, the
      effect of soy phytoestrogens on inflammation has not been studied
      comprehensively, especially in women receiving hormone replacement therapy (HRT).
      This study was conducted to determine whether adding soy to a low-fat, high-fiber
      diet affects CRP and interleukin (IL)-6, and to examine the association between
      CRP levels and lipid response in moderately hypercholesterolemic adults (men =
      18, postmenopausal women = 14; 6 receiving HRT). After a 3-wk run-in period with
      consumption of a Step I diet (27% total fat, 7% saturated fat, 275 mg
      cholesterol), participants were randomly assigned to diets containing 25 g/d soy
      protein (+ 90 mg/d isoflavones) or 25 g/d milk protein for 6 wk in a crossover
      design. Lipids and lipoproteins, CRP, and IL-6 were measured at the end of each
      diet and participants were categorized into high (>3.5 mg/L) or low CRP groups
      based on a median split. The addition of soy or milk protein to the Step I diet
      did not affect lipids or inflammatory markers. Regardless of protein source,
      those with low CRP exhibited significant decreases in LDL cholesterol (-3.5%) and
      the LDL:HDL cholesterol ratio (-4.8%), whereas those with high CRP had
      significant increases in LDL cholesterol (+4.8%), the LDL:HDL cholesterol ratio
      (+5.2%), apolipoprotein B (+3.8%), and lipoprotein(a) (+13.5%) compared with the
      run-in diet. These results suggest that inflammation may not only attenuate lipid
      responses, but also aggravate dyslipidemia in hypercholesterolemic subjects
      consuming a cholesterol-lowering diet.

PMID- 15867285
TI  - Casein and soy protein meals differentially affect whole-body and splanchnic
      protein metabolism in healthy humans.
AB  - Dietary protein quality is considered to be dependent on the degree and velocity
      with which protein is digested, absorbed as amino acids, and retained in the gut
      as newly synthesized protein. Metabolic animal studies suggest that the quality
      of soy protein is inferior to that of casein protein, but confirmatory studies in
      humans are lacking. The study objective was to assess the quality of casein and
      soy protein by comparing their metabolic effects in healthy human subjects. Whole
      body protein kinetics, splanchnic leucine extraction, and urea production rates
      were measured in the postabsorptive state and during 8-h enteral intakes of
      isonitrogenous [0.42 g protein/(kg body weight . 8 h)] protein-based test meals,
      which contained either casein (CAPM; n = 12) or soy protein (SOPM; n = 10) in 2
      separate groups. Stable isotope techniques were used to study metabolic effects.
      With enteral food intake, protein metabolism changed from net protein breakdown
      to net protein synthesis. Net protein synthesis was greater in the CAPM group
      than in the SOPM group [52 +/- 14 and 17 +/- 14 nmol/(kg fat-free mass (FFM) .
      min), respectively; P < 0.02]. Urea synthesis rates decreased during consumption
      of both enteral meals, but the decrease tended to be greater in the subjects that
      consumed CAPM (P = 0.07). Absolute splanchnic extraction of leucine was higher in
      the subjects that consumed CAPM [306 +/- 31 nmol/(kg FFM . min)] vs. those that
      consumed SOPM [235 +/- 29 nmol/(kg FFM . min); P < 0.01]. In conclusion, a
      significantly larger portion of soy protein is degraded to urea, whereas casein
      protein likely contributes to splanchnic utilization (probably protein synthesis)
      to a greater extent. The biological value of soy protein must be considered
      inferior to that of casein protein in humans.

PMID- 15867286
TI  - Aerobic exercise training decreases leucine oxidation at rest in healthy adults.
AB  - Both exercise and dietary protein intake affect whole-body protein turnover
      (WBPTO). Few studies have investigated the effect of aerobic exercise training on
      WBPTO [leucine rate of appearance (Ra), oxidation (Ox), and nonoxidative leucine
      disposal (NOLD)] in untrained individuals consuming a specified level of protein.
      This study examined the effect of aerobic exercise training on WBPTO in untrained
      men and women during a controlled diet intervention providing 0.88 g protein/(kg
      . d). After a 2-wk adaptation to the study diet, 7 subjects [3 men, 4 women; 76.1
      +/- 5.8 kg, 164.7 +/- 4.4 cm, 30.7 +/- 4.5% body fat, 39.1 +/- 2.8 VO(2max)
      (maximal oxygen uptake) mL/(kg . min)] participated in 4 wk of aerobic exercise
      training (running and walking 4-5 times/wk at 65-85% maximal heart rate). WBPTO
      (determined via constant infusion of 1-[(13)C] leucine), nitrogen balance, and
      body composition were determined at baseline and after 4 wk of training. Nitrogen
      balance (-1.0 +/- 0.7 vs. 0.9 +/- 1.1 g N/24 h, P = 0.03) improved with exercise
      training, whereas body mass and composition did not change. Leucine Ra did not
      change, Ox decreased [18 +/- 2 to 15 +/- 2 micromol/(kg . h), P </= 0.001], and
      NOLD tended to increase [128 +/- 18 to 151 +/- 19 micromol/(kg . h), P = 0.09] in
      response to training. These data indicate improved protein utilization in
      response to exercise training in weight-stable subjects. This study emphasizes
      the importance of dietary control, with specific regard to energy and protein
      intakes, in the characterization of protein utilization in response to an
      exercise intervention.

PMID- 15867287
TI  - Pill count adherence to prenatal multivitamin/mineral supplement use among low
      income women.
AB  - In the United States, the prevalence of third trimester anemia among low-income
      pregnant women is 29% and has not improved since the 1980s. Although low
      adherence has been linked to the ineffectiveness of iron supplementation
      programs, data regarding adherence to supplementation in low-income women are
      currently lacking. Hence this study was conducted to better understand the
      factors associated with adherence to the use of iron-containing prenatal
      multivitamin/mineral supplements among low-income pregnant women. Adherence to
      supplement use was assessed by pill counts among 244 pregnant women of 867 women
      who were initially randomized to receive 1 of 3 prenatal supplements. All women
      received care at a public prenatal clinic. Maternal characteristics associated
      with adherence were identified using predictive modeling. Women took 74% of
      supplements as prescribed. Adherence was higher among non-Hispanic white women
      than among non-Hispanic black women (79% vs. 72%, P </= 0.01). Interactions of
      ethnicity with age group, smoking status, and prior supplement use were
      significant. Multivariate regression analysis stratified by ethnicity revealed
      that among the white women education beyond high school, unmarried status,
      nulligravidity, and smoking were positively associated with adherence. In
      contrast, among the black women, supplement use 3 mo prior to current pregnancy
      and no loss of appetite were positively associated with adherence. Further
      research investigating the influence of cultural factors is necessary to better
      understand adherence to supplement use and the differences in adherence among
      ethnic groups.

PMID- 15867288
TI  - Zinc absorption from zinc oxide, zinc sulfate, zinc oxide + EDTA, or sodium-zinc
      EDTA does not differ when added as fortificants to maize tortillas.
AB  - The fortification of staple foods with zinc may play an important role in
      achieving adequate zinc intakes in countries at risk of zinc deficiency. However,
      little is known about the relative bioavailability of different zinc compounds
      that may be used in food fortification. The objective of this study was to
      measure and compare fractional zinc absorption from a test meal that included a
      maize tortilla fortified with zinc oxide, zinc sulfate, zinc oxide + EDTA, or
      sodium-zinc EDTA. A double isotopic tracer ratio method ((67)Zn as oral tracer
      and (70)Zn as intravenous tracer) was used to estimate zinc absorption in 42
      Mexican women living in a periurban community of Puebla State, Mexico. The test
      meal consisted of maize tortillas, yellow beans, chili sauce, and milk with
      instant coffee; it contained 3.3 mg zinc and had a phytate:zinc molar ratio of
      17. Fractional zinc absorption did not differ significantly between the test
      groups (ANOVA; P > 0.05). Percent absorptions were (mean +/- SD) zinc oxide, 10.8
      +/- 0.9; zinc sulfate, 10.0 +/- 0.02; zinc oxide + EDTA, 12.7 +/- 1.5; and sodium
      zinc EDTA, 11.1 +/- 0.7. We conclude that there was no difference in zinc
      absorption from ZnO and ZnSO(4) when added as fortificants to maize tortillas and
      consumed with beans and milk. The addition of EDTA with zinc oxide or the use of
      prechelated sodium-zinc EDTA as fortificants did not result in higher zinc
      absorption from the test meal.

PMID- 15867289
TI  - Micronutrient deficiencies in early pregnancy are common, concurrent, and vary by
      season among rural Nepali pregnant women.
AB  - Pregnant women in developing countries are vulnerable to multiple micronutrient
      deficiencies. We investigated their prevalence and seasonal variation as part of
      a baseline assessment in a population-based, maternal micronutrient
      supplementation trial conducted in the rural Southeastern plains of Nepal. Serum
      concentrations of 11 micronutrients were assessed in 1165 pregnant women in the
      1st trimester before supplementation. Using defined cutoff values, the prevalence
      of deficiencies of vitamins A, E, and D were 7, 25, and 14%, respectively. Nearly
      33% of the women were deficient in riboflavin, and 40 and 28% had serum vitamin B
      6 and B-12 deficiencies, respectively. Only 12% of the women were folate
      deficient, but 61% were zinc deficient. The prevalence of low serum iron
      concentration was 40%, and 33% were anemic (hemoglobin < 110 g/L). Multiple
      micronutrient deficiencies were common among pregnant women. Over 10% of the
      pregnant women were both anemic and deficient in B-complex vitamins, whereas 22%
      of women were both anemic and zinc deficient. Only 4% of women had no deficiency,
      whereas approximately 20% of the women had 2, 3, or 4 deficiencies. Almost 18% of
      women had >/=5 deficiencies. Micronutrient status varied by season; it was
      generally best during the winter months, except for serum vitamin D
      concentration, which peaked during the hot summer and monsoon months. Women in
      rural South Asia are likely to begin a pregnancy with multiple micronutrient
      deficiencies that may vary with seasonality in micronutrient-rich food
      availability.

PMID- 15867290
TI  - Use of population-specific infant mortality rates to inform policy decisions
      regarding HIV and infant feeding.
AB  - Mother-to-child transmission of HIV occurs during pregnancy, at the time of
      delivery, and through breastfeeding (BF). WHO recommends avoidance of all BF when
      replacement feeding (RF) is affordable, feasible, acceptable, sustainable, and
      safe. Otherwise, exclusive breastfeeding (EBF) followed by early BF cessation is
      recommended. Governments are currently scaling up programs to prevent infant HIV
      infection. Few data exist to guide policy decisions about the allocation of
      resources to prevent postnatal HIV transmission while minimizing the non-HIV
      related risks of these policies. This paper presents an analysis of the impact of
      WHO infant feeding recommendations in different settings characterized by infant
      mortality rate (IMR). Mathematical simulation modeling is used to estimate the
      effects on HFS (HFS) through 24 mo of 3 intervention scenarios: RF from birth by
      HIV-positive mothers (RF24), EBF up to 6 mo followed by early BF cessation
      (EBF6), and the default scenario where there is no postnatal intervention (BF24).
      This analysis differs from earlier reports in that it uses the most recent data
      on risks of postnatal HIV transmission for mixed and exclusive BF. These
      simulations suggest that in settings where IMR is <25/1000 live births, RF24
      results in the greatest HFS to 24 mo; EBF6 produces the best outcome where IMR >
      25/1000 live births. RF24 results in lower HFS than no postnatal intervention
      where IMR >/= 101/1000. IMR-based analyses can help to guide government policy
      decisions about which infant feeding strategies to invest in and emphasize for
      HIV-positive mothers in different settings.

PMID- 15867291
TI  - Mate drinking during pregnancy and risk of preterm and small for gestational age
      birth.
AB  - Mate, a hot infusion of Ilex paraguayensis, is a beverage largely consumed in
      Southeast Latin America, including during pregnancy. To assess the effect of mate
      drinking during pregnancy on preterm and small for gestational age (SGA) birth, a
      cross-sectional study was done. From January 1st to December 31st, 1993, in the
      first 24 h after delivery, all 5304 mothers giving birth at the hospitals in
      Pelotas, Southern Brazil, were interviewed and several of their characteristics
      were gathered. Birthweight was recorded and gestational age at birth assessed
      using the Dubowitz score. All 5189 single births were analyzed. The prevalence of
      SGA and preterm birth was 8.0 and 9.1%, respectively. Mate intake at least once a
      week during the entire pregnancy period was reported by approximately 68% of the
      mothers. Crude analyses showed a 30% increase in the risk of SGA among daily mate
      drinkers compared with nonconsumers (prevalence ratio = 1.3; 95% CI 1.1-1.6),
      whereas no statistical association was detected with preterm births. After
      controlling for confounders, the significance of the association with SGA birth
      no longer held and the lack of association with prematurity remained unchanged.
      In conclusion, prevalence of daily mate drinking was high among pregnant women
      and, contrary to the hypothesis, no harmful effect on intrauterine growth or
      duration of pregnancy was detected.

PMID- 15867292
TI  - The combination of dietary conjugated linoleic acid and treadmill exercise lowers
      gain in body fat mass and enhances lean body mass in high fat-fed male Balb/C
      mice.
AB  - Nearly half of the U.S. adult population is overweight or obese, which may be
      related to increased energy intake combined with lack of physical activity.
      Obesity increases the risk of several chronic diseases including diabetes,
      coronary heart disease, hypertension, and stroke. Conjugated linoleic acids (CLA)
      were shown to decrease fat and increase lean mass in several animal studies.
      However, the effects of CLA in combination with exercise (Ex) on body composition
      have not been studied in an animal model. We examined the effect of a low
      concentration of either safflower oil as control (0.5%) or mixed isomers of CLA
      (0.4%) along with treadmill exercise on body composition in male Balb/C mice fed
      a high-fat diet (20% corn oil) in a 2 x 2 factorial design. CLA consumption
      lowered change in fat mass (P < 0.001) confirming the results of other studies,
      and change in fat mass decreased further (P < 0.001) with CLA and exercise.
      Change in lean mass did not increase with exercise alone; it increased, although
      not significantly, with CLA alone and increased significantly (P < 0.05) due to
      the combination of CLA and exercise. This effect was accompanied by decreased
      serum leptin levels and lower leptin mRNA expression in peritoneal fat (P <
      0.001). Serum insulin, glucose, tumor necrosis factor (TNF)-alpha, and
      interleukin-6 were lower in CLA-fed mice than in controls (P < 0.05), whereas
      serum TNF-alpha was increased by exercise (P < 0.05). Exercise increased oxygen
      consumption and energy expenditure when measured under resting conditions (P <
      0.05). In summary, the combination of dietary CLA and exercise decreased fat mass
      and increased lean mass in mice fed a high-fat diet, and these effects may be
      related in part to decreased serum leptin and exercise-induced increases in
      oxygen consumption and energy expenditure.

PMID- 15867293
TI  - Mineral absorption and excretion as affected by microbial phytase, and their
      effect on energy metabolism in young piglets.
AB  - Positive effects of dietary phytase supplementation on pig performance are
      observed not only when phosphorus is limiting. Improved energy utilization might
      be one explanation. Using indirect calorimetry, phytase-induced changes in energy
      metabolism were evaluated in young piglets with adequate phosphorus intake. Eight
      replicates of 8 group-housed barrows each were assigned to either a control or a
      phytase-supplemented diet [1500 phytase units (FTU)/kg feed]. Piglets were fed a
      restricted amount of the control or phytase diet. The diets were made limiting in
      energy content by formulating them to a high digestible lysine:DE ratio. Fecal
      nutrient digestibility, portal blood variables, organ weights, and apparent
      absorption and urinary excretion of ash, Ca, P, Na, K, Mg, Cu, and Fe, were also
      measured. A model was developed to estimate energy required for absorption and
      excretion, which are partly active processes. Phytase tended to improve energy
      digestibility (P = 0.10), but not its metabolizability. Energy retention and heat
      production were not affected. At the end of the 3-wk period, pancreas weight (P <
      0.05) and blood pH were lower (P < 0.01), and CO(2) pressure was higher (P <
      0.01) due to phytase. This suggests that phytase reduced energy expenditure of
      the digestive tract, and increased metabolic activity in visceral organs. The
      potential increases in energy retention due to phytase were counterbalanced by
      increased energy expenditures for processes such as increased mineral absorption
      (for most P < 0.05), and their subsequent urinary excretion. Energy costs of
      increased absorption of nutrients, and deposition and excretion of minerals was
      estimated as 4.6 kJ/(kg(0.75) . d), which is 1% of the energy required for
      maintenance. The simultaneous existence of both increases and decreases in heat
      production processes resulted in the absence of a net effect on energy retention.

PMID- 15867294
TI  - A long-term controlled folate feeding study in young women supports the validity
      of the 1.7 multiplier in the dietary folate equivalency equation.
AB  - The presence of folic acid in enriched cereal grain products and the higher
      bioavailability of folic acid than food folate led to the expression of the 1998
      folate RDA, 400 microg/d, as dietary folate equivalents (DFE). DFE are defined
      as: mug natural food folate + 1.7 x microg synthetic folic acid. The 1.7
      multiplier was based on assumptions that added folic acid was 85% available and
      food folate was 50% available. The 85/50 ratio also inferred that the
      bioavailability of food folate was approximately 60% relative to added folic
      acid. The objective of this long-term controlled feeding study was to assess the
      dietary folate equivalency of folic acid. After a 2-wk period of folate
      restriction, women (n = 42, 18-45 y old) consumed either 400 or 800 microg DFE/d
      derived from various combinations of food folate and folic acid for 12 wk. Folic
      acid was converted to DFE using the 1.7 multiplier from the DFE calculation and
      was consumed with a meal throughout the treatment period. Folate status response
      to the various treatments was assessed during wk 12-14. Serum folate, RBC folate,
      and plasma total homocysteine did not differ among the 400 microg DFE/d groups or
      among the 800 microg DFE/d groups. In contrast, consumption of 800 microg DFE/d
      led to higher (P </= 0.05) serum and RBC folate than consumption of 400 microg
      DFE/d. These data support the validity of the 1.7 multiplier in the DFE equation
      and suggest that food folate bioavailability is approximately 60% that of added
      folic acid when consumed as part of a mixed diet.

PMID- 15867295
TI  - Arginine supplementation enhances mitogen-induced splenocyte proliferation but
      does not affect in vivo indicators of antigen-specific immunity in mice.
AB  - Arginine is a conditionally essential amino acid with many physiologic roles. Its
      role in immune function has been one of major focus with conflicting results.
      Early in vitro immune studies demonstrated increased mitogen-induced lymphocyte
      proliferation with dietary arginine supplementation; however, not all studies
      confirmed this effect. Even less is known about the effect of arginine
      supplementation on in vivo immune responses. To test whether arginine
      supplementation enhances in vivo indicators of immune function, young female
      BALB/c mice were fed either the AIN-93G rodent diet (6.4 g arginine/kg diet) or
      the same diet with 20 g total arginine/kg diet for 15 d before delayed-type
      hypersensitivity (DTH) testing with 2,4-dinitrofluorobenzene (n = 16-18/diet
      group). The same mice were challenged with influenza virus A/Port Chalmers/1/73
      (H3N2) 15 d later. Mice were killed 3, 6, or 31 d postinfluenza challenge (5
      6/diet group on each day). Mitogen-induced splenocyte proliferation, body weight,
      anti-influenza serum antibody, lung viral titers, and serum arginine were
      measured. DTH did not differ between diet groups. On d 6 and 31 postchallenge,
      mitogen-induced proliferation of splenocytes from mice fed the arginine diet was
      >1.5-fold that of mice fed the control diet (P < 0.05). Body weight and influenza
      lung viral and serum antibody titers did not differ between diet groups. These
      data suggest that despite significant enhancement of in vitro mitogen-induced
      splenocyte proliferation, arginine supplementation does not have a biologically
      significant effect on antigen-specific in vivo indicators of immune function in
      this model.

PMID- 15867296
TI  - Dietary (n-3) polyunsaturated fatty acids do not affect the in vivo development
      and function of Listeria-specific CD4+ and CD8+ effector and memory/effector T
      cells in mice.
AB  - We previously reported that in a mouse model, a diet high in (n-3) PUFA
      diminishes host survival following an infection from Listeria monocytogenes, a
      gram-positive bacterial pathogen. In this study we investigated the impact of (n
      3) PUFA on the adaptive immune response to L. monocytogenes. BALB/c mice were fed
      experimental diets either devoid of or rich in (n-3) PUFA from fish oil for 4 wk
      and then infected with 10(6) actA-deficient L. monocytogenes. At 7 and 35 d
      postchallenge, effector and memory/effector T cells in the spleen were enumerated
      by flow cytometry. Surprisingly, the number of Listeria-specific CD4(+) and
      CD8(+) effector and memory/effector T cells in the spleen was not affected by (n
      3) PUFA. Also, the effector cells derived from mice fed either diet were equally
      capable of conferring protective immunity upon adoptive transfer to naive
      recipients. Despite our previous data, which demonstrated that (n-3) PUFA
      profoundly impaired host resistance to L. monocytogenes, pathogen-specific T cell
      responses were not substantially affected by dietary (n-3) PUFA.

PMID- 15867297
TI  - alpha-Tocopherol and selenium facilitate recovery from lipopolysaccharide-induced
      sickness in aged mice.
AB  - The elderly suffer a decline in immune function that increases their
      vulnerability to infections. Because antioxidants improve some age-related
      deficits in immune and cognitive function, our goal was to determine whether
      dietary alpha-tocopherol (alpha-T) and selenium inhibit LPS-induced sickness
      behavior in aged mice. Male BALB/c mice were fed modified AIN93-M diets that were
      low, adequate, or high in both alpha-T (10, 75, or 500 mg/kg) and selenium (0.05,
      0.15, or 2 mg/kg) from 18 to 21 mo of age. Sickness was quantified by measuring
      time in social exploration of a novel juvenile conspecific. The
      lipopolysaccharide treatment reduced social exploration by 74% at 2 h, regardless
      of diet. By 4 h, aged mice fed the low diet were 88% less social, whereas mice
      fed the adequate and high diets displayed only approximately 40% reductions due
      to LPS treatment. Mice fed the low diet had greater LPS-induced weight loss than
      mice fed the high diet. Plasma alpha-T concentration and glutathione peroxidase
      (GPX) activity increased with each increment in alpha-T and selenium 24 h post
      LPS treatment. Brain alpha-T concentration and GPX activity were lower in mice
      fed the low diet than in those fed the adequate or high diet. Regardless of diet,
      interleukin (IL)-6, IL-1beta, and tumor necrosis factor (TNF)alpha mRNA levels
      were elevated by LPS approximately 3-fold in cortex, cerebellum, striatum, and
      hippocampus. Thus, antioxidants inhibit sickness behavior independently of IL-6,
      IL-1beta, and TNFalpha mRNA levels 2 h post-LPS in the brain regions analyzed.
      Taken together, these findings suggest that adequate intake of dietary alpha-T
      and selenium may help promote recovery from gram-negative bacterial infection in
      the aged.

PMID- 15867298
TI  - Bovine glycomacropeptide is anti-inflammatory in rats with hapten-induced
      colitis.
AB  - Milk kappa-casein-derived glycomacropeptide has immunomodulatory and bacterial
      toxin binding effects. The intestinal anti-inflammatory activity of
      glycomacropeptide was assessed in trinitrobenzenesulfonic acid-induced colitis in
      rats. Rats were administered glycomacropeptide daily starting either 2 d before
      (pretreatment) or 3 h after (post-treatment) colitis induction. Pretreatment with
      glycomacropeptide had a dose-dependent anti-inflammatory effect, characterized by
      lower body weight loss, decreased anorexia (57%), colonic damage (65%), and
      weight to length ratio (32%), as well as a reduction in colonic alkaline
      phosphatase activity (42%) and interleukin 1, trefoil factor 3, and inducible
      nitric oxide synthase mRNA levels (P < 0.05). The mechanism of action of
      glycomacropeptide is unknown but is consistent with an inhibition of the
      activation of immune cells. The magnitude of the anti-inflammatory effect was
      generally comparable to that of sulfasalazine, an established drug used in the
      treatment of inflammatory bowel disease. Bovine glycomacropeptide may play a role
      in the management of patients with inflammatory bowel disease.

PMID- 15867299
TI  - Enterococcus faecium SF68 enhances the immune response to Giardia intestinalis in
      mice.
AB  - We studied the ability of the probiotic organism Enterococcus faecium SF68 to
      antagonize Giardia intestinalis infection in mice. Oral feeding of E. faecium
      strain SF68 starting 7 d before inoculation with Giardia trophozoites
      significantly increased the production of specific anti-Giardia intestinal IgA
      and blood IgG. This humoral response was mirrored at the cellular level by an
      increased percentage of CD4(+) T cells in the Peyer's patches and in the spleens
      of SF68-fed mice. The improvement of specific immune responses in probiotic-fed
      mice was associated with a diminution in the number of active trophozoites in the
      small intestine as well as decreased shedding of fecal Giardia antigens (GSA65
      protein). The ability of SF68 to stimulate the immune system at both mucosal and
      systemic levels highlights mechanisms by which this probiotic might antagonize
      pathogens in vivo. Taken together, the data demonstrate the strong potential of
      strain SF68 to prevent protozoa from causing intestinal infections.

PMID- 15867300
TI  - A statistical approach based on substitution of macronutrients provides
      additional information to models analyzing single dietary factors in relation to
      type 2 diabetes in danish adults: the Inter99 study.
AB  - Most studies analyzing diet-disease relations focus on single dietary factors
      rather than combining different nutrients into the same statistical model. The
      objective of this study was to identify dietary factors associated with the
      probability of having diabetes identified by screening (SDM) in Danish men and
      women aged 30-60 y. A specific objective was to examine whether an alternative
      statistical approach could provide additional information to already existing
      statistical approaches used in nutritional epidemiology. Baseline data from the
      Danish population-based Inter99 study were used. The dietary intake of 262
      individuals with SDM was compared with that of 4627 individuals with normal
      glucose tolerance (NGT) using 2 different types of multiple logistic regression
      models adjusted for potential confounders. The first model included single
      dietary factors, whereas the second model was based on substitution of
      macronutrients. In the models with single dietary factors, high intakes of
      carbohydrates, dietary fiber, and coffee were inversely associated with SDM (P <
      0.01), whereas high intakes of total fat and saturated fat were positively
      associated with SDM (P < 0.05). A modest U-shaped association was found between
      alcohol consumption and SDM (P = 0.10) [corrected] Results from the substitution
      model showed that when 3% of energy (En%) as carbohydrate replaced 3 En% fat or
      alcohol, the probability of having SDM decreased by 9 and 10%, respectively (P <
      0.01) [corrected] No other macronutrient substitutions resulted in significant
      associations. Hence, the statistical approach based on substitution of
      macronutrients provided additional information to the model analyzing single
      dietary factors.

PMID- 15867301
TI  - Identification of a food pattern characterized by high-fiber and low-fat food
      choices associated with low prospective weight change in the EPIC-Potsdam cohort.
AB  - The aim of the study was to identify a dietary pattern predictive of subsequent
      annual weight change by using dietary composition information. Study subjects
      were 24,958 middle-aged men and women of the European Prospective Investigation
      into Cancer and Nutrition-Potsdam cohort. To derive dietary patterns, we used the
      reduced rank regression method with 3 response variables presumed to affect
      weight change: fat density, carbohydrate density, and fiber density. Annual
      weight change was computed by fitting a linear regression line to each person's
      body weight data (baseline, and 2- and 4-y follow-up) and determining the slope.
      In linear regression models, the pattern score was related to annual weight
      change. We identified a food pattern of high consumption of whole-grain bread,
      fruits, fruit juices, grain flakes/cereals, and raw vegetables, and of low
      consumption of processed meat, butter, high-fat cheese, margarine, and meat to be
      predictive of subsequent weight change. Mean annual weight gain gradually
      decreased with increasing pattern score (P for trend < 0.0001), i.e., subjects
      scoring high for the pattern maintained their weight or gained significantly less
      weight over time compared with subjects with an opposite pattern. However, the
      prediction of annual weight change by the food pattern was significant only in
      nonobese subjects. In this study population, we identified a food pattern
      characterized by high-fiber and low-fat food choices that can help to maintain
      body weight or at least prevent excess body weight gain.

PMID- 15867302
TI  - Higher dietary intake of lignans is associated with better cognitive performance
      in postmenopausal women.
AB  - Data on the relation between phytoestrogens and cognitive function are still
      sparse. The purpose of this study was to examine the relation between the dietary
      intake of phytoestrogens and cognitive function in healthy postmenopausal women
      consuming a Western diet. We conducted a community-based survey among 394
      postmenopausal women. Isoflavone and lignan intake was calculated from a
      validated FFQ. Cognitive function was evaluated using the Mini-Mental State
      Examination (MMSE). Data were analyzed using logistic regression with intact
      cognitive function defined as a score >/= 26 as the outcome variable. After
      adjustment for confounders, increasing dietary lignans intake was associated with
      better performance on the MMSE [OR and (95%CI): 1.49 (0.94-2.38)]. Results were
      most pronounced in women who were 20-30 y postmenopausal [2.02 (1.11-3.71)].
      Isoflavone intake was not related to cognitive function. From our results we
      conclude that higher dietary intake of lignans is associated with better
      cognitive function in postmenopausal women.

PMID- 15867303
TI  - Protein intake is inversely associated with abdominal obesity in a multi-ethnic
      population.
AB  - Abdominal obesity is related to significant morbidity and mortality and differs
      by ethnicity; however, the relation between diet and abdominal obesity has not
      been extensively studied. The aim of this study was to evaluate the dietary and
      lifestyle determinants of abdominal obesity in a multi-ethnic population. We
      conducted a cross-sectional study among 617 Canadians of Aboriginal, South Asian,
      Chinese, and European origins, with diet evaluated using validated, culture
      specific, interviewer-administered FFQs, and abdominal obesity measured as waist
      hip ratio (WHR). The mean proportion of energy intake from protein in the diet
      was 17.4 vs. 15.8% comparing the lowest and highest tertiles of WHR. Energy
      adjusted protein substituted for an equivalent amount of carbohydrate was
      associated with a reduction in WHR (difference in WHR for every g/d increase in
      protein intake = -0.0005, P = 0.01) after accounting for age, sex, ethnicity,
      smoking status, BMI, alcohol intake, height, physical activity, and total energy.
      Fat or total energy were not related to WHR in the same linear regression model.
      Smoking was positively and physical activity inversely related to WHR in the
      multivariate model independent of BMI and other potential confounders.
      Substituting a modest amount of protein for carbohydrate may reduce abdominal
      obesity in a diverse multi-ethnic population. Smoking was positively related to
      abdominal obesity after accounting for BMI.

PMID- 15867304
TI  - Intake of the plant lignans secoisolariciresinol, matairesinol, lariciresinol,
      and pinoresinol in Dutch men and women.
AB  - Enterolignans (enterolactone and enterodiol) are phytoestrogens that are formed
      by the colonic microflora from plant lignans. They may reduce the risk of certain
      types of cancer and cardiovascular diseases. Initially, only secoisolariciresinol
      and matairesinol were considered to be enterolignan precursors, but recently, new
      precursors such as lariciresinol and pinoresinol were identified. We recently
      developed a lignan database including 4 major enterolignan precursors. We used
      this database to estimate lignan intake in a representative sample of Dutch men
      and women participating in the Dutch Food Consumption Survey, carried out in 1997
      1998. Median total lignan intake among 4660 adults (19-97 y old) was 979
      microg/d. Total lignan intake did not differ between men and women; thus, the
      lignan density of the diet was significantly higher (P < 0.001) in women than in
      men. Lignan intake was strongly skewed toward higher values (range 43-77584
      microg/d, mean 1241 microg/d). Lariciresinol and pinoresinol contributed 75% to
      lignan intake, whereas secoisolariciresinol and matairesinol contributed only
      25%. The major food sources of lignans were beverages (37%), vegetables (24%),
      nuts and seeds (14%), bread (9%), and fruits (7%). Lignan intake was
      significantly (P < 0.001) correlated with intake of dietary fiber (r = 0.46),
      folate (r = 0.39), and vitamin C (r = 0.44). Older persons, nonsmokers,
      vegetarians, and persons with a low BMI or a high socioeconomic status had higher
      lignan intakes than their counterparts. In brief, this study shows that the
      amount of enterolignan precursors in the diet has previously been largely
      underestimated.

PMID- 15867305
TI  - Diet and serum carotenoid concentrations affect macular pigment optical density
      in adults 45 years and older.
AB  - The dietary carotenoids lutein (L) and zeaxanthin (Z) are the principal
      components of macular pigment (MP). Protection of the central retina by MP is
      suggested, but data are limited. Dietary practices and serum carotenoid
      concentrations were investigated in 98 adults, 45-73 y old, in relation to MP.
      Macular pigment optical density (MPOD) was measured at 4 loci: 10 min (10', 30
      min (30'), 60 min (60'), and 120 min (120') retinal eccentricity. Serum L + Z
      concentrations in fasting subjects were correlated with MPOD: 10' (r = 0.29, P =
      0.008), 30' (r = 0.342, P = 0.0006), and 60' (r = 0.73, P = 0.001) eccentricity.
      Dietary L + Z was positively correlated with MPOD: 10' (r = 0.24, P = 0.02), 30'
      (r = 0.237, P = 0.02), 60' (r = 0.27, P = 0.009), and 120' (r = 0.25, P = 0.02)
      eccentricity. The lowest fruit and vegetable consumers had lower MPOD at 30' (P =
      0.01), 60' (P = 0.03), and 120' (P = 0.006) eccentricity compared with the
      highest consumers. Based on age quartiles (45-49 y), (50-55 y), (56-61 y), and
      (62-74 y), the youngest and oldest had higher MPOD than those 56-61 y at 60' (P <
      0.05). Compared with those with a BMI (kg/m(2)) >/= 27, those with a BMI < 27 had
      higher serum concentrations of beta-carotene (P = 0.002), and higher MPOD at 60'
      (P = 0.04) and 120' (P = 0.01). These findings suggest that carotenoid-rich diets
      and serum carotenoids positively contribute to MP status.

PMID- 15867306
TI  - Identification of dietary and endogenous ileal protein losses in pigs by
      immunoblotting and mass spectrometry.
AB  - Ileal flows and the endogenous or dietary origin of soluble proteins present in
      ileal digesta were determined in pigs fed diets containing different pea
      cultivars (Solara, Madria and Eiffel) and micro-ground peas (c.v. Solara). Ileal
      digesta proteins were analyzed by electrophoresis and densitometry analysis and
      were identified by LC-MS-MS spectrometry and immunoblotting. The ileal flows of
      proteins differed (P < 0.1) among the 3 pea cultivars; the flow in pigs fed the
      Madria-containing diet was higher than that of pigs fed the Eiffel- and Solara
      containing diets. The flow was reduced by micro-grinding the peas. The true
      digestibility of pea proteins and the endogenous losses were not correlated.
      However, at this intestinal level, protein losses were essentially of endogenous
      origin (enzymes, antibodies), and from the partly digested pea albumin fraction.
      Pea lectin and albumin PA1b were totally resistant to gastric and small
      intestinal digestion and a minor resistant peptide from pea albumin PA2 was
      detectable. In contrast, the storage proteins, legumin and vicilin, were not
      detectable by antibodies or by LC-MS-MS.

PMID- 15867307
TI  - Component interactions for efficacy of functional foods.
AB  - The study of functional foods appears to hold the promise of improved quality of
      life, particularly for older persons who fight chronic disease. Many laboratories
      are studying the mechanisms of action of individual bioactive food components;
      but, relatively few studies are concerned with the interaction of the many
      components found in a single food or with a comparison between effects of the
      putative major bioactive component and the whole food. This overview is an
      introduction to the papers that follow, which were given as a symposium at the
      2004 Experimental Biology meetings and which address the interactive effects of
      bioactive food components, particularly those in soy, broccoli, berries, and
      tomatoes. However, conclusions to be drawn go further than these 4 foods. The
      studies act as examples, identifying needed areas of focus in the study of
      functional foods and specifically the need for research into functional foods to
      encompass 3 areas of study: strength in chemical analysis, mechanistic studies
      carried out in cell culture, and animal studies comparing effects of dietary
      exposure to purified components and whole foods. Together, data from these 3
      areas can give the solid scientific basis needed, so that clinical studies can be
      properly planned and executed.

PMID- 15867308
TI  - The tomato as a functional food.
AB  - Tomatoes are the fourth most commonly consumed fresh vegetable and the most
      frequently consumed canned vegetable in the American diet. There is emerging
      epidemiology data supporting the connection between increased tomato consumption
      and reduced risk for both cardiovascular disease and prostate cancer. Here we
      will summarize the nutrient and the phytochemical content of tomatoes and tomato
      products, and how these bioactive components might act together to modulate
      disease development. Recent animal studies have investigated tomatoes, lycopene,
      and prostate cancer using the N-methyl-N-nitrosourea and Dunning rat models.
      These animal studies also suggest that diets containing tomatoes may decrease the
      risk or the progression of prostate cancer. Due to the frequency and the extent
      of tomato consumption, the supporting epidemiological and animal data, which
      connect increased intakes with decreased cancer and cardiovascular disease risk,
      tomato's role in the American diet is of undeniable importance as part of a
      healthy diet.

PMID- 15867309
TI  - Sorting out bioactivity in flavonoid mixtures.
AB  - Natural polyphenolic compounds, including flavonoids, which are synthesized by
      plants, have repeatedly been linked to multiple health benefits, but specific
      bioactive compounds or individualized roles have been difficult to interpret or
      to assign. This limitation has prevented the development of robust dietary
      recommendations. This paper describes a plant-cell-culture production approach
      that provides uniform yields of abundant natural mixtures of flavonoids from
      small molecules to high molecular weight oligomers and polymers. The flavonoids
      correspond to compounds produced in nature by the same plant genotypes; but,
      through elicitation tactics, the levels and the profiles of the flavonoid yield
      can be enhanced, and isolation from cell cultures is more rapid and streamlined
      than isolation from in vivo plant tissues. Introduction of (14)C sucrose to the
      cell-culture medium enabled the recovery and the identification of biolabeled
      flavonoid mixtures, which could be easily tracked in serum of rats after gavage.
      The biolabeled materials are now being investigated to determine tissue
      localization, structures of bioactive components, and the interactions between
      flavonoid components that contribute to bioactive potential.

PMID- 15867310
TI  - Selenium enrichment of broccoli: interactions between selenium and secondary
      plant compounds.
AB  - Multiple components of broccoli, such as sulforaphane (Sf) and phenolic acids,
      may inhibit cancer. Additionally, broccoli can accumulate selenium (Se), and Se
      has been demonstrated to reduce the risk of cancer. Studies were conducted to
      determine whether enhancement of broccoli with Se would produce a plant with
      superior health benefits. Although increasing the concentration of Se in broccoli
      from <1.0 to >800 microg/g resulted in inhibition of colon cancer in rats, it
      also decreased the Sf content by >80% and inhibited production of most phenolic
      acids. The inclusion of Se-enriched broccoli in the diet of rats induced the
      activity of the selenoprotein thioredoxin reductase beyond the maximum activity
      induced by Se alone. These results emphasize the complex interactions of
      bioactive chemicals in a food; attempts to maximize one component may affect
      accumulation of another, and consumption of high amounts of multiple bioactive
      compounds may result in unexpected metabolic interactions within the body.

PMID- 15867311
TI  - Environmental influences on isoflavones and saponins in soybeans and their role
      in colon cancer.
AB  - Soybeans have long been recognized as an excellent source of high-quality
      protein. The soybean also contains a wide variety of chemical compounds that have
      potent bioactivity. Among these compounds are the isoflavones and the saponins.
      The goal of our research was to quantify isoflavone and saponin concentrations in
      elite soybean cultivars grown in different environments and to identify a
      naturally occurring high and low variety that could be used in animal studies of
      colon cancer. We observed significant environment x genotype interactions for the
      cultivars and selected 2 that provided the range of concentration for isoflavones
      and saponins. These were grown in an adequate quantity for animal studies, which
      are ongoing. We explored the influence of isoflavones and saponins on human colon
      tumor cells in culture, Caco-2, to determine potential mechanisms through which
      these compounds influence the carcinogenic process. We observed the inhibition of
      Caco-2 cell proliferation by isoflavones and saponins, suggesting a protective
      effect of these compounds in colon cancer. Using purified soy saponins, we found
      no negative effects on mouse growth, organ weights, or intestinal morphology when
      the diet contained up to 3% saponins by weight. Hence, soy isoflavones and
      saponins are likely to be protective of colon cancer and to be well tolerated.
      Continuing studies will explore the cancer-protective effects of these compounds
      in animal models.

PMID- 15867312
TI  - Soy isoflavones and bone health: the relationship is still unclear.
AB  - Evidence of the effect of purified soy isoflavones and soy protein isolates
      containing isoflavones on bone health in rats and in humans is inconsistent.
      Differences may be because of synergies or antagonisms among the isoflavones,
      threshold or biphasic dose effects, life stage of animals or human subjects,
      estrogen status, and environment-genetic interactions, including the ability to
      produce metabolites upon ingestion of isoflavones. At this time, the benefits of
      soy protein and isoflavones on bone health are inconclusive. This overview will
      summarize these discrepancies and will suggest future studies to clarify the
      conditions under which these dietary substances can be helpful for bones.

PMID- 15867313
TI  - X-train: teaching professionals remotely.
AB  - Increased popularity of the Internet, along with the development of new software
      applications have dramatically improved our ability to create and deliver online
      continuing education trainings to professionals in the areas of nutrition and
      food safety. In addition, these technological advances permit effective and
      affordable measurement of training outcomes, i.e., changes in knowledge,
      attitude, and behavior, that result from these educational efforts. Impact
      assessment of engagement programs is becoming increasing important for
      demonstrating the value of training activities to stakeholders. A novel software
      program, called X-Train, takes advantage of technological advances (databases,
      computer graphics, Web-based interfaces, and network speed) for delivering high
      quality trainings to teachers and health care professionals. X-Train
      automatically collects outcome data, and generates and sends certificates of
      completion and communicates with participants through electronic messages. X
      Train can be used as a collaborative tool whereby experts from various academic
      institutions are brought together to develop Web-based trainings. Finally, X
      Train uses a unique approach that encourages cooperative extension specialists
      and educators to promote these educational opportunities within their state or
      county.

PMID- 15867314
TI  - Functional foods: delivering information to the oncology nurse.
AB  - Recent research suggests a beneficial role of nutrition as possible supportive
      therapy for cancer patients. A national survey of oncology nurses has shown that
      nutrition-related issues are an important subject discussed during nurse-patient
      meetings. The authors applied the activation theory of information exposure to
      oncology nurses in regard to nutrition information. Findings suggest that
      oncology nurses who consider nutrition important at a personal level tend to
      discuss nutrition more with patients and to seek more information about nutrition
      and cancer. Personal rather than professional motives appear to be triggers for
      the information search. Implications for health care communication professionals
      are discussed.

PMID- 15867315
TI  - Introduction to a history of nutrition symposium concerning the Interdepartmental
      Committee on Nutrition for National Defense.

PMID- 15867316
TI  - Origins of the Interdepartmental Committee on Nutrition for National Defense, and
      a brief note concerning its demise.
AB  - The Interdepartmental Committee on Nutrition for National Defense was established
      in 1955 after malnutrition was found common among troops of the Republic of Korea
      and of the Republic of China (Taiwan). The initial purpose was identification of
      nutrition problems among military personnel (later, and among civilians) of
      countries of "special interest." Surveys measured status, assisted with the
      establishment of nutrition resources, and facilitated investigator learning and
      research. A major initial accomplishment was the preparation of a manual of
      procedures, which evolved into the 1963 Manual for Nutrition Surveys. The first 3
      surveys, conducted in 1956, were of the armies of Iran, Pakistan, and Korea. They
      identified poor nutrition status in some troops, provided a basis for improving
      rations, and confirmed the effectiveness of the methodology. These surveys were
      followed by surveys of 30 additional countries that in nearly all instances
      included civilians and provided a basis for programs and the institutions for
      improvement of nutrition. On August 1, 1967, the program was reorganized and the
      Nutrition Program, CDC, based at NIH, was created. This occurred in response to
      the 1967 Partnership for Health Amendments "to make a comprehensive survey of the
      incidence and location of serious hunger and malnutrition, and health problems
      incident thereto, in the United States and to report these conditions to the
      Congress." The Ten State Nutrition Survey was done in response. Findings of
      malnutrition, especially in populations of low-income states were politically
      unwelcome in some quarters. Consequently the program was redirected, and,
      according to 2 observers, the survey findings were suppressed.

PMID- 15867317
TI  - History of Interdepartmental Committee on Nutrition for National Defense: course
      of events and nutrition methodology in typical surveys.
AB  - It was my good fortune to help brief many of the survey teams on dietary methods
      and to serve on 2 survey teams. Dr. Arnold E. Schaefer, executive director of the
      International Committee on Nutrition for National Defense (ICNND), dictated his
      reflections, which I edited, for the symposium, "Reflections of Dr. Arnold E.
      Schaefer." The course of events in a typical ICNND nutrition survey were
      described. This included the following: 1) protocol, 2) organization of survey
      team, appropriate for the country, 3) briefing of team members, 4) provision of
      needed equipment and supplies, and 5) planning the survey with the host country.
      The advance mission visit usually included Dr. Frank Berry, assistant secretary
      of Defense for Health and the ICNND executive director, who briefed local
      government officials about the survey. The supply and the equipment needs
      included clinical and laboratory equipment, reference books and supplies needed
      for routine physical examinations, dietary studies, and laboratory
      determinations. Host countries provided 1) personnel to serve on survey teams, 2)
      logistical support, and 3) unbiased random population samples for clinical and
      dietary studies. The methods of measuring dietary intake used are described in
      the manual. Measuring the nutrient intake of military personnel is usually much
      less difficult than of civilians. The food preparation and consumption (recipe)
      and food composite analysis methods were most commonly used. The diet
      questionnaire used for civilians, recorded amounts of specific foods consumed the
      previous day (24-h recall). During the Ecuador survey, Combs and Wolfe obtained
      similar results with the recipe, the food composite, and the 24-h recall methods
      in the same 28 families.

PMID- 15867318
TI  - Medical examination in nutrition surveys.
AB  - Pellagra was the most important deficiency disease used as a model for nutrition
      surveys, because its diagnosis depended on physical signs. By the mid twentieth
      century, laboratory tests improved the specificity of physical signs in diagnosis
      of deficiency disease. The author uses his experience in Panama to illustrate how
      attention to the details of a medical examination can improve accuracy and
      sensitivity of a nutrition survey.

PMID- 15867319
TI  - The story of the Interdepartmental Committee on Nutrition for National Defense's
      North American activities (1958-1970).
AB  - Of the 48 nutrition surveys conducted by the ICNND/Office of International
      Research/CDC Nutrition Programs during the years 1956-1970, 20 were performed in
      North America. Native Americans were surveyed in Alaska in 1958 and in Montana in
      1961. In partnership with INCAP (Institute for Central America and Panama), six
      Central American countries were surveyed in 1965 through 1967. As mandated by
      Congress, 10 American states and one major city were surveyed during 1968-1970.
      Civilian and some military populations were included in these surveys. Teams of
      health, agriculture, and nutrition specialists drawn from academic institutions
      and from national and international agencies conducted each survey. We followed
      the methodology, standards, and definitions developed by ICNND in its Manual for
      Nutrition Surveys. Detailed findings, results and recommendations were published
      in a series of reports printed by the U.S. Government Printing Office. All 20 of
      the North American surveys found similar groups at risk of nutrition problems,
      including dental caries, goiter, growth retardation, female obesity, and "low"
      levels of hemoglobin, vitamin A, thiamin, and riboflavin. Survey recommendations
      followed common themes: nutrition education, nutrient fortification of food or
      water, expanded supplemental food programs, provision of safe water supplies,
      proper sanitation and food safety, and enhanced nutrient content of basic foods.

PMID- 15867320
TI  - Interdepartmental Committee on Nutrition for National Defense surveys in Asia and
      Africa.
AB  - I suppose I should establish my bonafides for participation in this symposium. I
      did participate in 3 Interdepartmental Committee on Nutrition for National
      Defense (ICNND) surveys as far separated as one on the Blackfeet Indian
      Reservation (1) in Montana and 2 in Asia-Burma (2) and East Pakistan (3). In
      fact, the Blackfeet Reservation and Burma surveys were my training grounds for
      becoming the clinical chief for the East Pakistan survey and later the
      codirector. More importantly, in 1962, I followed Alan Forbes, who is much missed
      at this symposium, as the deputy to Arnie Schaefer at ICNND and NIH, and did have
      experience of an office in the Stone House on the NIH campus. There I
      participated in the transmutation of the ICNND to the Interdepartmental Committee
      on National Development and its alignment with the Office of International
      Research at the NIH and a repositioning within the Department of Health and Human
      Services. It was from this position that ICNND went on to organize some civilian
      surveys in the mid-1960s, including those in Central America and Panama (4), and
      it was from this position that the groundwork was laid for the application of
      ICNND techniques to the first U.S. domestic survey outside of an Indian
      reservation, culminating in the Ten State Nutrition Survey (5), which documented
      that there was hunger in America, as well as abroad.

PMID- 15867321
TI  - The Interdepartmental Committee on Nutrition for National Defense surveys:
      lasting impacts.
AB  - The Interdepartmental Committee on Nutrition for National Defense (ICNND) Surveys
      provided previously unavailable representative information on the food and
      nutrition situations of military or civilian populations in 33 developing
      countries. Information on related social and economic conditions also were
      assessed. These data provided a framework for planning follow-up programs to
      correct problems identified and to prevent them from recurring, such as
      fortification of salt with iodine and sugar with vitamin A. Educational materials
      specific to the nutrient content of local foods, dietary patterns, and
      availability within countries and cultures were also developed, such as food
      composition tables and dietary guidelines. In-country scientists were motivated
      to continue nutrition research, and, in several countries, institutes and
      departments of nutrition evolved. Impact was documented by improved nutritional
      status in several countries, although success is not always attributed directly
      to the impetus provided through the ICNND Surveys. Furthermore, the surveys and
      their leaders provided inspiration and role models for aspiring young
      nutritionists both within their own countries and internationally.

PMID- 15867322
TI  - Nutrition surveys in Burma and northeast Brazil.
AB  - Participation of the author in the Interdepartmental Committee on Nutrition for
      National Defense sponsored nutrition surveys of Burma and northeast Brazil is
      described. These surveys not only collected important data on nutritional status
      but also guided the subsequent research interests of the author. The Brazil
      survey results contributed to the creation of legislation that mandated the
      addition of water-dispersible vitamin A to skimmed-milk powder products. This
      additive has greatly diminished the likelihood of vitamin A deficiency syndrome
      occurring in children after famine relief efforts.

PMID- 15867323
TI  - Reminiscence concerning the Interdepartmental Committee on Nutrition for National
      Defense.

PMID- 15867324
TI  - Interdepartmental Committee on Nutrition for National Defense memories.

PMID- 15867325
TI  - Human milk inactivates pathogens individually, additively, and synergistically.
AB  - Breast-feeding can reduce the incidence and the severity of gastrointestinal and
      respiratory infections in the suckling neonate by providing additional protective
      factors to the infant's mucosal surfaces. Human milk provides protection against
      a broad array of infectious agents through redundancy. Protective factors in milk
      can target multiple early steps in pathogen replication and target each step with
      more than one antimicrobial compound. The antimicrobial activity in human milk
      results from protective factors working not only individually but also additively
      and synergistically. Lipid-dependent antimicrobial activity in milk results from
      the additive activity of all antimicrobial lipids and not necessarily the
      concentration of one particular lipid. Antimicrobial milk lipids and peptides can
      work synergistically to decrease both the concentrations of individual compounds
      required for protection and, as importantly, greatly reduce the time needed for
      pathogen inactivation. The more rapidly pathogens are inactivated the less likely
      they are to establish an infection. The total antimicrobial protection provided
      by human milk appears to be far more than can be elucidated by examining
      protective factors individually.

PMID- 15867326
TI  - Antimicrobial peptides in mucosal secretions: the importance of local secretions
      in mitigating infection.
AB  - The antimicrobial activity of the collective molecules comprising human milk
      reflects an evolutionarily successful paradigm for preventing and limiting
      microbial infection. Understanding the molecules that participate in this process
      and how they work can yield insight into potentially new antimicrobial therapies.
      Upon proteolytic processing, antimicrobial peptides can be derived from milk
      proteins, such as lactoferrin, casein, and lysozyme. Similarly, using the HIV-1
      gp41 protein template, we have demonstrated that the 28-residue C-terminus, when
      produced as an independent peptide, exhibits selective toxicity for bacteria over
      eukaryotic cells. Upon optimizing this sequence for cationic charge and
      hydrophobic character presented as a alpha-helical structure, we show improved
      capability of the parent LLP1 sequence to selectively kill bacteria in the host
      environment and that this activity is increased by the inclusion of Trp residues
      on the hydrophobic face. We report that it is possible to (i) design de novo
      antimicrobial peptides that demonstrate optimal antimicrobial activity with
      minimal inflammatory activity and (ii) design antimicrobial peptides to function
      in a defined environment. In the end, we describe a de novo designed
      antimicrobial peptide, WLBU2, which is selectively toxic to microbial pathogens
      in complex environments and does not stimulate a significant immunomodulatory
      response. In spite of these properties, WLBU2 activity against Pseudomonas
      aeruginosa in human milk is inferior to the host peptide LL37 with regard to
      antimicrobial potency. These studies demonstrate that antimicrobial peptides can
      be engineered for greater potency in one medium but may not be optimal for
      working in a different medium such as human milk.

PMID- 15867327
TI  - Probiotics that modify disease risk.
AB  - Probiotics are defined as live bacterial preparations with clinically documented
      health effects in humans. Probiotics have specific properties and targets in the
      human intestinal tract and intestinal microbiota. Each probiotic strain,
      independent of its genus and species is unique and, thus, the properties and the
      human health effects of each strain have to be assessed in a case-by-case manner.
      Understanding the mechanisms by which probiotics influence the normal intestinal
      microbiota and counteract aberrancies in microbiota would facilitate the use of
      probiotics for both dietary management and reduction in risk of specific
      diseases. Development of intestinal microbiota is an important factor affecting
      the health of the newborn. Recent studies suggest that specific bacterial
      components, especially the bifidobacteria, have a key impact on development of a
      healthy balanced infant microbiota. The composition of infant and child
      intestinal microbiota may become aberrant and thus influence the development of
      diarrheal, inflammatory, and allergic diseases. Based on this understanding,
      positive health effects of probiotics have been reported in the management of
      diarrheal, inflammatory, and allergic diseases in infants. Most recently, a
      reduction in risk of atopic diseases followed early administration of specific
      probiotics.

PMID- 15867328
TI  - HAMLET kills tumor cells by apoptosis: structure, cellular mechanisms, and
      therapy.
AB  - New cancer treatments should aim to destroy tumor cells without disturbing normal
      tissue. HAMLET (human alpha-lactalbumin made lethal to tumor cells) offers a new
      molecular approach to solving this problem, because it induces apoptosis in tumor
      cells but leaves normal differentiated cells unaffected. After partial unfolding
      and binding to oleic acid, alpha-lactalbumin forms the HAMLET complex, which
      enters tumor cells and freezes their metabolic machinery. The cells proceed to
      fragment their DNA, and they disintegrate with apoptosis-like characteristics.
      HAMLET kills a wide range of malignant cells in vitro and maintains this activity
      in vivo in patients with skin papillomas. In addition, HAMLET has striking
      effects on human glioblastomas in a rat xenograft model. After convection
      enhanced delivery, HAMLET diffuses throughout the brain, selectively killing
      tumor cells and controlling tumor progression without apparent tissue toxicity.
      HAMLET thus shows great promise as a new therapeutic with the advantage of
      selectivity for tumor cells and lack of toxicity.

PMID- 15867329
TI  - Human-milk glycans that inhibit pathogen binding protect breast-feeding infants
      against infectious diarrhea.
AB  - Breast-feeding is a highly effective strategy for preventing morbidity and
      mortality in infancy. The human-milk glycans, which include oligosaccharides in
      their free and conjugated forms, constitute a major and an innate immunologic
      mechanism by which human milk protects breast-fed infants against infections. The
      glycans found in human milk function as soluble receptors that inhibit pathogens
      from adhering to their target receptors on the mucosal surface of the host
      gastrointestinal tract. The alpha1,2-linked fucosylated glycans, which require
      the secretor gene for expression in human milk, are the dominant glycan structure
      found in the milk of secretor mothers, who constitute the majority (
      approximately 80%) of mothers worldwide. In vitro and in vivo binding studies
      have demonstrated that alpha1,2-linked fucosylated glycans inhibit binding by
      campylobacter, stable toxin of enterotoxigenic Escherichia coli, and major
      strains of caliciviruses to their target host cell receptors. Consistent with
      these findings, recently published epidemiologic data demonstrate that higher
      relative concentrations of alpha1,2-linked fucosylated glycans in human milk are
      associated with protection of breast-fed infants against diarrhea caused by
      campylobacter, caliciviruses, and stable toxin of enterotoxigenic E. coli, and
      moderate-to-severe diarrhea of all causes. These novel data open the potential
      for translational research to develop the human-milk glycans as a new class of
      antimicrobial agents that prevent infection by acting as pathogen anti-adhesion
      agents.

PMID- 15867330
TI  - Innate immunity and human milk.
AB  - Human neonates are born with an immature and naive acquired immune system, and
      many of the innate components of mucosal immunity are not fully developed. Thus,
      the innate immune system of human milk is an important complement to the mucosal
      barrier of the developing gut. The nursing mother provides her infant many
      protective agents through milk, a growing number of which have been identified as
      isolates of milk in laboratory models of infection. The number, the potency, and
      the importance of these protective agents are probably greater than previously
      thought. For example, many potent protective agents are not found in milk until
      digestion releases antimicrobial agents such as fatty acids and peptides. An
      alternate conformer of alpha-lactalbumin forms from milk in the stomach and
      inhibits cancer cells. Many of the protective constituents of human milk inhibit
      different aspects of a pathogenic process, creating a synergy, where much lower
      concentrations of each component become protective. Some components have a
      temporal and a spatial specificity that would cause their protective role to go
      unrecognized by most laboratory models of infection. Some protective components
      had remained underappreciated because of technical challenges in their isolation
      and testing. Recent reports suggest that human milk contains a highly potent
      mixture of protective agents that constitute an innate immune system, whereby the
      mother protects her infant from enteric and other diseases. These human-milk
      components may represent a rich source of novel classes of therapeutic agents
      against human pathogens.

PMID- 15867331
TI  - Ghrelin: its role in energy balance.

PMID- 15867332
TI  - Obesity and the neuroendocrine control of energy homeostasis: the role of
      spontaneous locomotor activity.
AB  - Obesity represents one of the most urgent global health threats as well as one of
      the leading causes of death throughout industrialized nations. Efficacious and
      safe therapies remain at large. Attempts to decrease fat mass via pharmacological
      reduction of energy intake have had limited potency or intolerable side effects.
      Increasingly widespread sedentary lifestyle is often cited as a major contributor
      to the increasing prevalence of obesity. Moreover, low levels of spontaneous
      physical activity (SPA) are a major predictor of fat mass accumulation during
      overfeeding in humans, pointing to a substantial role for SPA in the control of
      energy balance. Despite this, very little is known about the molecular mechanisms
      by which SPA is regulated. The overview will attempt to summarize available
      information on neuroendocrine factors regulating SPA.

PMID- 15867333
TI  - Regulation of ghrelin in physiologic and pathophysiologic states.
AB  - Ghrelin, a ligand for the growth hormone secretagogue receptor, is an orexigenic
      hormone produced in the gastrointestinal tract. In humans and other animals,
      circulating ghrelin levels fluctuate over the course of the day in relation to
      food intake. If circulating ghrelin plays a role in determining food intake from
      meal to meal, it will be important to understand the factors that regulate plasma
      ghrelin levels in relation to feeding. Circulating ghrelin levels also appear to
      reflect body weight changes over the longer term, raising the possibility that
      ghrelin functions as an adiposity signal. This review discusses some of the
      factors known to affect ghrelin levels, including nutrient stimulation of the
      gastrointestinal tract, diet composition, and weight loss. We also consider
      potential hormonal and neural mediators of the effects of nutrients and weight
      change on ghrelin levels.

PMID- 15867334
TI  - Plasma ghrelin concentrations are lower in binge-eating disorder.
AB  - Binge-eating disorder (BED), characterized by binge meals without purging
      afterward, is found in about 30% of obese individuals seeking treatment. The
      study objective was to ascertain abnormalities in hormones influencing appetite
      in BED, especially ghrelin, an appetite-stimulating peptide, which was expected
      to be elevated. Measurements were made of plasma insulin, leptin, glucagon,
      cholecystokinin, and ghrelin, as well as glucose following an overnight 12-h
      fast, prior to and after ingestion (from 0 to 5 min) of a nutritionally complete
      liquid meal (1254 kJ) at 0830 h, at -15, 0, 5, 15, 30, 60, 90, and 120 min.
      Appetite ratings including hunger and fullness were also obtained. An
      acetaminophen tracer was used to assess gastric emptying rate. Three groups of
      comparably obese women (BMI = 35.9 +/- 5.5; % body fat = 44.9 +/- 4.7)
      participated: 12 nonbinge eating normals (NB), 14 subthreshold BED, and 11 BED.
      The BED subjects, compared to NB subjects, had lower baseline ghrelin
      concentrations prior to the meal, a lower area under the curve (AUC), with lower
      levels at 5, 15, 30, 90, and 120 min, and a smaller decline in ghrelin postmeal
      (all P < 0.03). The other blood values did not differ among groups, and neither
      did gastric emptying rate nor ratings of fullness. The BED subjects were then
      randomly assigned to treatment with cognitive-behavior therapy and diet (n = 5)
      or to a wait-list control (n = 4). Baseline ghrelin (P = 0.01) and AUC increased
      (P = 0.02), across both conditions, in which most subjects (7 of 9) stopped binge
      eating. The lower fasting and postmeal plasma ghrelin levels in BED are
      consistent with lower ghrelin levels in obese compared to lean individuals and
      suggests downregulation by binge eating.

PMID- 15867335
TI  - Stimulation of appetite by ghrelin is regulated by leptin restraint: peripheral
      and central sites of action.
AB  - A reciprocal rhythmic pattern of 2 afferent hormonal signals, anorexigenic leptin
      and orexigenic ghrelin, imparts rhythmicity to the neuropeptide Y (NPY) system,
      the final common pathway for appetite expression in the hypothalamus. We now show
      that leptin inhibits both the secretion of gastric ghrelin and the stimulation of
      feeding by ghrelin. We propose that this dual leptin restraint is the major
      regulatory arm of the feedback communication between the periphery and the
      hypothalamus for weight homeostasis, and disruption in the rhythmic communication
      at any locus in the leptin-ghrelin-NPY feedback loop impels loss of hypothalamic
      control, leading to abnormal weight gain and obesity.

PMID- 15867336
TI  - Effect of added sugars on dietary quality.

PMID- 15867337
TI  - Role of the Ras-association domain family 1 tumor suppressor gene in human
      cancers.
AB  - In recent years, the list of tumor suppressor genes (or candidate TSG) that are
      inactivated frequently by epigenetic events rather than classic mutation/deletion
      events has been growing. Unlike mutational inactivation, methylation is
      reversible and demethylating agents and inhibitors of histone deacetylases are
      being used in clinical trails. Highly sensitive and quantitative assays have been
      developed to assess methylation in tumor samples, early lesions, and bodily
      fluids. Hence, gene silencing by promoter hypermethylation has potential clinical
      benefits in early cancer diagnosis, prognosis, treatment, and prevention. The
      hunt for a TSG located at 3p21.3 resulted in the identification of the RAS
      association domain family 1, isoform A gene (RASSF1A). RASSF1A falls into the
      category of genes frequently inactivated by methylation rather than mutational
      events. This gene is silenced and frequently inactivated by promoter region
      hypermethylation in many adult and childhood cancers, including lung, breast,
      kidney, gastric, bladder, neuroblastoma, medulloblastoma, gliomas and it has
      homology to a mammalian Ras effector (i.e., Nore1). RASSF1A inhibits tumor growth
      in both in vitro and in vivo systems, further supporting its role as a TSG. We
      and others identified the gene in 2000, but already there are over a 150
      publications demonstrating RASSF1A methylation in a large number of human
      cancers. Many laboratories including ours are actively investigating the biology
      of this novel protein family. Thus far, it has been shown to play important roles
      in cell cycle regulation, apoptosis, and microtubule stability. This review
      summarizes our current knowledge on genetic, epigenetic, and functional analysis
      of RASSF1A tumor suppressor gene and its homologues.

PMID- 15867338
TI  - MicroRNA biogenesis and cancer.
AB  - MicroRNAs (miRNA) are a recently discovered family of short non-protein-coding
      RNAs that negatively regulate gene expression. Recent studies of miRNAs highlight
      a requirement for cell viability. Posttranscriptional silencing of target genes
      by miRNAs occurs either by targeting specific cleavage of homologous mRNAs, or by
      targeting specific inhibition of protein synthesis. We recently identified a
      multisubunit protein complex termed Microprocessor that is necessary and
      sufficient for processing miRNA precursor RNAs. Microprocessor contains Drosha,
      an RNase III endonuclease, and DGCR8, a gene deleted in DiGeorge syndrome. We
      consider recent findings that link miRNA perturbation to cancer.

PMID- 15867339
TI  - Meeting report: the role of telomeres and telomerase in cancer.
AB  - The role of telomeres and telomerase in cancer is an area of much recent
      interest. This conference sponsored by the American Association of Cancer
      Research provided a timely opportunity to bring together basic and clinical
      scientists interested in the field of telomeres and telomerase cancer biology.
      The meeting included over 250 attendees with 150 oral and poster presentations
      focused on understanding telomere and telomerase biology for the development of
      cancer therapeutics. The meeting chairpersons were Dr. Jerry W. Shay, University
      of Texas Southwestern Medical Center, Dallas, TX; Dr. Elizabeth H. Blackburn,
      University of California San Francisco, CA; and Dr. Maria A. Blasco, Spanish
      National Cancer Center, Madrid, Spain. The meeting provided an update on the
      field, pointing to areas in which our knowledge is deficient, and explored how
      the most promising areas may be advanced into translational research. This
      conference brought together cell and molecular biologists with clinicians
      interested in fundamental cancer mechanisms as they relate to telomeres and
      telomerase. The symposium consisted of formal presentations by prominent
      scientists working in these areas and by participants selected from submitted
      abstracts. In addition, there were two poster sessions. Whereas there were many
      basic research advances presented, the focus of this overview will be the areas
      of clinical advances.

PMID- 15867340
TI  - An identity crisis for fps/fes: oncogene or tumor suppressor?
AB  - Fps/Fes proteins were among the first members of the protein tyrosine kinase
      family to be characterized as dominant-acting oncoproteins. Addition of
      retroviral GAG sequences or other experimentally induced mutations activated the
      latent transforming potential of Fps/Fes. However, activating mutations in
      fps/fes had not been found in human tumors until recently, when mutational
      analysis of a panel of colorectal cancers identified four somatic mutations in
      sequences encoding the Fps/Fes kinase domain. Here, we report biochemical and
      theoretical structural analysis demonstrating that three of these mutations
      result in inactivation, not activation, of Fps/Fes, whereas the fourth mutation
      compromised in vivo activity. These results did not concur with a classic
      dominant-acting oncogenic role for fps/fes involving activating somatic mutations
      but instead raised the possibility that inactivating fps/fes mutations might
      promote tumor progression in vivo. Consistent with this, we observed that tumor
      onset in a mouse model of breast epithelial cancer occurred earlier in mice
      targeted with either null or kinase-inactivating fps/fes mutations. Furthermore,
      a fps/fes transgene restored normal tumor onset kinetics in targeted fps/fes null
      mice. These data suggest a novel and unexpected tumor suppressor role for Fps/Fes
      in epithelial cells.

PMID- 15867341
TI  - Antimetastatic activity of a novel mechanism-based gelatinase inhibitor.
AB  - Matrix metalloproteinases (MMPs), and in particular gelatinases (MMP-2 and MMP
      9), play a key role in cancer progression. However, clinical trials in which MMP
      inhibitors were tested in cancer patients have been disappointing. Whereas many
      reasons have been postulated to explain the failure of the clinical trials, lack
      of inhibitor selectivity was a major limitation. Thus, despite the consensus
      opinion that MMP-mediated proteolysis is essential for cancer progression and
      that certain MMPs represent important targets for intervention, effective and
      selective inhibition of those MMPs remains a major challenge in drug development.
      We previously reported the first mechanism-based MMP inhibitor, designated SB
      3CT, which is a selective gelatinase inhibitor. Here we report that SB-3CT (5-50
      mg/kg/d) is a potent inhibitor of liver metastasis and increases survival in an
      aggressive mouse model of T-cell lymphoma. This study shows that mechanism-based
      inhibition of gelatinases represents a novel approach to inhibitor design that
      promises to be a successful anticancer therapy.

PMID- 15867342
TI  - Genotype-dependent induction of transmissible chromosomal instability by gamma
      radiation and the benzene metabolite hydroquinone.
AB  - Although it is well established that ionizing radiation and benzene are
      epidemiologically linked to acute myeloid leukemia (AML), the underlying
      mechanisms are not understood. We have shown that gamma-radiation can induce a
      persisting genomic instability in the clonal descendants of hemopoietic stem
      cells manifested as a high frequency of nonclonal chromosome and chromatid
      aberrations. A strikingly similar instability is shown after exposure to the
      benzene metabolite hydroquinone. The CBA/Ca but not the C57BL/6 genotype is
      susceptible to the induction of instability by both ionizing radiation and
      hydroquinone and exposure of CBA/Ca, but not C57BL/6, mice to either agent is
      known to be associated with the development of AML. The results are consistent
      with the proposal that chromosomal instability induced by either agent may
      contribute to AML development by increasing the number of genetic lesions in
      hemopoietic cells. Genotype-dependent chromosomal instability can be induced by
      hydroquinone doses that are not acutely stem cell toxic and this may have
      important implications for current assessment of safe levels of exposure to
      benzene as well as for mechanistic understanding of the hemotoxic and
      leukemogenic effects.

PMID- 15867343
TI  - A survivin gene signature predicts aggressive tumor behavior.
AB  - Gene signatures that predict aggressive tumor behavior at the earliest stages of
      disease, ideally before overt tissue abnormalities, are urgently needed. To
      search for such genes, we generated a transgenic model of survivin, an essential
      regulator of cell division and apoptosis overexpressed in cancer. Transgenic
      expression of survivin in the urinary bladder did not cause histologic
      abnormalities of the urothelium. However, microarray analysis revealed that
      survivin-expressing bladders exhibited profound changes in gene expression
      profile affecting extracellular matrix and inflammatory genes. Following exposure
      to a bladder carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN),
      survivin transgenic animals exhibited accelerated tumor progression, preferential
      incidence of tumors as compared with premalignant lesions, and dramatically
      abbreviated survival. Conversely, transgenic expression of a survivin Thr34-->Ala
      dominant-negative mutant did not cause changes in gene expression or accelerated
      tumor progression after OH-BBN treatment. Therefore, survivin expression induces
      global transcriptional changes in the tissue microenvironment that may promote
      tumorigenesis. Detection of survivin or its associated gene signature may provide
      an early biomarker of aggressive tumor behavior before the appearance of tissue
      abnormalities.

PMID- 15867344
TI  - Implication of galectin-3 in Wnt signaling.
AB  - Galectin-3 (gal-3), a member of the beta-galactoside-binding proteins family, was
      identified as a binding partner of beta-catenin. Analysis of the human gal-3
      sequence reveled a structural similarity to beta-catenin as it also contains the
      consensus sequence (S92XXXS96) for glycogen synthase kinase-3beta (GSK-3beta)
      phosphorylation and can serve as its substrate. In addition, Axin, a regulator
      protein of Wnt that complexes with beta-catenin, also binds gal-3 using the same
      sequence motif identified here by a deletion mutant analysis. The data presented
      here give credence to the suggestion that gal-3 is a key regulator in the
      Wnt/beta-catenin signaling pathway and highlight the functional similarities
      between gal-3 and beta-catenin.

PMID- 15867345
TI  - ZD6474 suppresses oncogenic RET isoforms in a Drosophila model for type 2
      multiple endocrine neoplasia syndromes and papillary thyroid carcinoma.
AB  - Patients with hereditary medullary thyroid carcinoma (MTC) associated with
      multiple endocrine neoplasia (MEN) types 2A and 2B and familial MTC (FMTC) have
      mutations in the RET proto-oncogene. Approximately 40 percent of patients with
      papillary thyroid carcinoma (PTC) typically have either intrachromosomal or
      extrachromosomal rearrangements that join the promoter and NH(2)-terminal domains
      of unrelated genes to the COOH-terminal fragment of RET. The RET point mutations
      associated with MEN2A, MEN2B, or FMTC, or the chromosomal breakpoints and
      translocations associated with PTC, typically activate the RET receptor tyrosine
      kinase (RTK). RET kinase inhibitors are likely to be beneficial for patients with
      hereditary MTC, where currently there is no effective chemotherapy or radiation
      therapy. Recently, the low molecular weight tyrosine kinase inhibitor ZD6474 was
      found to block the enzymatic activity of RET-derived oncoproteins in cultured
      cell lines. We have developed a Drosophila model for MEN2A and MEN2B diseases by
      targeting oncogenic forms of RET to the developing Drosophila eye. Here we show
      that, when fed orally, ZD6474 suppressed RET-mediated phenotypes within the
      context of this in vivo model. Importantly, ZD6474 showed high efficacy and very
      low toxicity. This compound failed to significantly suppress an activated form of
      another RTK, the Drosophila epidermal growth factor receptor, nor did it suppress
      the activity of downstream components of the RET/Ras pathway. Our results support
      the view that targeting chemical kinase inhibitors such as ZD6474 to tissues with
      oncogenic forms of RET is a useful treatment strategy for RET-dependent
      carcinomas.

PMID- 15867346
TI  - SWI/SNF chromatin-remodeling factors induce changes in DNA methylation to promote
      transcriptional activation.
AB  - Brahma (Brm) and brahma-related gene-1 (Brg1) are mammalian homologues of SWI/SNF
      chromatin-remodeling factor subunits that can regulate both transcriptional
      activation and repression. Both Brg1 and Brm are mutated or deleted in numerous
      cancer cell lines, leading to the altered expression of genes that influence cell
      proliferation and metastasis. Here, we find that the promoters of two such genes,
      CD44 and E-cadherin, are hypermethylated in cells that have lost Brg1 or Brm. In
      two carcinoma cell lines that lack functional Brg1 and Brm, CD44 and E-cadherin
      expression are induced by the demethylating agent 5-aza-2'-deoxycytidine.
      Transfection with either Brg1 or Brm also induces CD44 and E-cadherin
      transcription and protein expression in these cells, as well as loss of
      methylation at sequences in the promoters of both genes. Chromatin
      immunoprecipitation assays show that Brg1 and Brm associate with these regions of
      the CD44 and E-cadherin promoters, suggesting that SWI/SNF protein complexes may
      directly influence the loss of DNA methylation. In vivo, Brm-deficient mice also
      show methylation and silencing of the CD44 promoter. Collectively, these data
      implicate loss of SWI/SNF-mediated transcriptional activation as a novel
      mechanism to increase DNA methylation in cancer cells and provide insight into
      the mechanisms underlying aberrant gene induction and repression during tumor
      progression.

PMID- 15867347
TI  - Two functional coding single nucleotide polymorphisms in STK15 (Aurora-A)
      coordinately increase esophageal cancer risk.
AB  - STK15/Aurora-A is a serine/threonine kinase essential for chromosome segregation
      and cytokinesis, and is considered to be a cancer susceptibility gene in mice and
      humans. Two coding single nucleotide polymorphisms in Aurora-A, 91T>A
      [phenylalanine/isoleucine (F/I)] and 169G>A [valine/isoleucine (V/I)], create
      four haplotypes, 91T-169G, 91A-169G, 91T-169A, and 91A-169A. We evaluated the
      association between these coding single nucleotide polymorphisms and esophageal
      cancer risk by genotyping 197 esophageal cancer cases and 146 controls. Haplotype
      91A-169A (I31/I57) was observed to be statistically more frequent in cancer cases
      (odds ratio, 3.1452; 95% confidence interval, 1.0258-9.6435). Functional
      differences among the four isoforms were then analyzed to reveal the source of
      the cancer risk. Kinase activity levels of I31/I57 and F31/I57 were reduced to
      15% and 40% compared with I31/V57 in vivo and in vitro. We considered the
      differences between the kinase activities and divided individuals into four
      categories of Aurora-A haplotype combination. Category I had 57.5% or less kinase
      activity compared with the most common category, category III, and had a
      significantly higher estimated cancer risk (odds ratio, 5.5328; 95% confidence
      interval, 1.8149-16.8671). Abnormal nuclear morphology, a characteristic of
      genomic instability, was observed to be 30 to 40 times more frequent in human
      immortalized fibroblast cells overexpressing I31/I57 or F31/I57 compared with the
      others. Furthermore, significantly higher levels of chromosomal instability were
      observed in cancers in category I (homozygote 91T-169A) than those in category
      III (homozygous 91A-169G). These results indicate that the less kinase active
      Aurora-A haplotype combinations might induce genomic instability and increase
      esophageal cancer risk either in a recessive or a dominant manner.

PMID- 15867348
TI  - Dominant-negative Notch3 receptor inhibits mitogen-activated protein kinase
      pathway and the growth of human lung cancers.
AB  - Notch3 is a member of an evolutionarily conserved family of cell surface
      receptors important in cell-fate determination in both vertebrates and
      invertebrates. Significant data support the role of Notch pathway in cancer
      development, although the conflicting role of Notch signaling pathways in
      tumorigenesis suggests that its action is highly context-dependent. Furthermore,
      although Notch receptors signal primarily through the regulation of hairy
      enhancer of split (HES) and HES-related (HRT) genes, they are known to crosstalk
      with other signaling pathways, including the epidermal growth factor (EGF) and
      the mitogen-activated protein kinase pathways. Whereas much is known about the
      role of Notch1 in human cancer, the role of Notch3 in epithelial tumors, such as
      lung carcinomas, has not been well established. In this study, we show that
      Notch3 is expressed in 80 of 207 (39%) resected human lung tumors and that its
      expression is positively correlated with EGF receptor expression. Inhibition of
      the Notch3 pathway using a dominant-negative receptor dramatically reduces growth
      in soft agar and increases growth factor dependence. We also find that Notch
      inhibition increases sensitivity to EGF receptor tyrosine kinase inhibition and
      decrease in phosphorylation of the mitogen-activated protein kinase. These
      observations support a role for Notch3 signaling in lung cancer, and one
      potential mechanism of maintaining the neoplastic phenotype is through the
      modulation of the EGF pathway.

PMID- 15867349
TI  - Inactivation of the invasion inhibitory gene IIp45 by alternative splicing in
      gliomas.
AB  - The invasion inhibitory protein 45 (IIp45) we recently identified was
      underexpressed in glioblastoma multiforme, the most malignant form of glioma. The
      IIp45 gene is located at chromosome 1p36 where frequent deletions have been
      reported in various types of tumors, including gliomas, raising the possibility
      that IIp45 may be a classic tumor suppressor gene that can be inactivated by
      frequent point mutations. To test this hypothesis, we sequenced the IIp45 gene in
      59 diffuse glioma samples of different grades and histologic subtypes and
      identified a possible point mutation or a rare polymorphism in only one sample
      (1.7%), suggesting that IIp45 is not a classic tumor suppressor gene such as p53.
      Instead, reverse transcription-PCR and subsequent sequencing results revealed a
      tumor-specific IIp45 spliced isoform (IIp45S) in 20 of 59 (34%) gliomas examined,
      particularly in glioblastoma multiformes, including native tissue samples (15 of
      25; 60%) and cell lines (5 of 5; 100%). The alternative splicing event is
      independent of 1p36 deletion, which is not common in glioblastoma multiforme. The
      IIp45S transcript was not detected in any of 18 normal organs, including fetal
      and adult brain. We determined that the IIp45S isoform results from exclusion of
      IIp45 exon 7 and encodes a variant protein that carries a COOH terminus different
      from that of IIp45 due to a frame-shift mutation. IIp45S protein was undetectable
      in glioma tissues, although IIp45S mRNA was prevalent. We found that IIp45S, once
      translated, is rapidly degraded by an ubiquitin-proteasome mechanism. Thus, the
      IIp45 gene is inactivated by a tumor-specific alternative splicing that generates
      an aberrant and unstable IIp45 isoform in infiltrative gliomas.

PMID- 15867350
TI  - Pulmonary radiation injury: identification of risk factors associated with
      regional hypersensitivity.
AB  - Effective radiation treatment of thoracic tumors is often limited by
      radiosensitivity of surrounding tissues. Several experimental studies have
      suggested variations in radiosensitivity of different pulmonary regions. Mice and
      rat studies in part contradict each other and urge for a more detailed analysis.
      This study was designed to obtain a more comprehensive insight in radiation
      injury development, expression, and its regional heterogeneity in lung. The
      latter is obviously highly critical for optimization of radiotherapy treatment
      plans and may shed light on the mechanisms of lung dysfunction after irradiation.
      Six different but volume-equal regions in rat lung were irradiated. Whereas the
      severity of damage, as seen in histologic analysis, was comparable in all
      regions, the degree of lung dysfunction, measured as breathing rates, largely
      varied. During the pneumonitic phase (early: 6-12 weeks), the most sensitive
      regions contained a substantial part of alveolar lung parenchyma. Also, a trend
      for hypersensitivity was observed when the heart lay in the irradiation field. In
      the fibrotic phase (late: 34-38 weeks), lung parenchyma and heart-encompassing
      regions were the most sensitive. No impact of the heart was observed during the
      intermediate phase (16-28 weeks). The severity of respiratory dysfunction after
      partial thoracic irradiation is likely governed by an interaction between
      pulmonary and cardiac functional deficits. As a repercussion, more severe acute
      and delayed toxicity should be expected after combined lung and heart
      irradiation. This should be considered in the process of radiotherapy treatment
      planning of thoracic malignancies.

PMID- 15867351
TI  - Patches of mutant p53-immunoreactive epidermal cells induced by chronic UVB
      Irradiation harbor the same p53 mutations as squamous cell carcinomas in the skin
      of hairless SKH-1 mice.
AB  - Treatment of SKH-1 hairless mice with UVB (30 mJ/cm(2)) twice a week for 20 weeks
      results in the formation of cellular patches, long before the appearance of
      tumors, that are visualized in epidermal sheets with an antibody (PAb240)
      recognizing mutated p53 protein. Direct sequencing analysis of the whole coding
      region of the p53 gene (exons 2-11) detected one or two mutations in 64.4% of 104
      analyzed patches and no mutations in nonstained adjacent normal controls.
      Homozygous mutation was detected in 22.4% of the mutant patches. Except for two
      nonsense mutations, all others were missense (exons 4-9) and mostly (95.5%) at
      the DNA-binding domain. Primer extension analysis of cloned PCR fragments found
      three of four double-mutated patches harboring different mutations in separate
      alleles. All mutation hotspots reported earlier in UVB-induced mouse squamous
      cell carcinomas (SCC) at codons 270 (Arg --> Cys), 149 (Pro --> Ser), 275 (Pro -
      > Leu and Pro --> Ser), and 176 (His --> Tyr) with a frequency of 32.1%, 7.1%,
      14.7%, and 3.2% were detected in epidermal patches at a frequency 47.7%, 9.1%,
      4.5%, and 2.3%, respectively. Mutations at codons 210 and 191 found in patches at
      respective frequencies of 8.0% and 4.5% were not previously detected in UVB
      induced mouse SCC. In summary, (a) the p53 mutation profile of UVB-induced skin
      patches and SCC was very similar suggesting that patches are precursor lesions
      for SCC, (b) a small number of patches harbored mutations that were not before
      observed in SCC from UVB-treated mice, and (c) about 36% of the patches did not
      harbor a p53 mutation.

PMID- 15867352
TI  - Breast cancer metastasis suppressor 1 inhibits gene expression by targeting
      nuclear factor-kappaB activity.
AB  - Breast cancer metastasis suppressor 1 (BRMS1) functions as a metastasis
      suppressor gene in breast cancer and melanoma cell lines, but the mechanism of
      BRMS1 suppression remains unclear. We determined that BRMS1 expression was
      inversely correlated with that of urokinase-type plasminogen activator (uPA), a
      prometastatic gene that is regulated at least in part by nuclear factor-kappaB
      (NF-kappaB). To further investigate the role of NF-kappaB in BRMS1-regulated gene
      expression, we examined NF-kappaB binding activity and found an inverse
      correlation between BRMS1 expression and NF-kappaB binding activity in MDA-MB-231
      breast cancer and C8161.9 melanoma cells stably expressing BRMS1. In contrast,
      BRMS1 expression had no effect on activation of the activator protein-1
      transcription factor. Further, we showed that suppression of both constitutive
      and tumor necrosis factor-alpha-induced NF-kappaB activation by BRMS1 may be due
      to inhibition of IkappaBalpha phosphorylation and degradation. To examine the
      relationship between BRMS1 and uPA expression in primary breast tumors, we
      screened a breast cancer dot blot array of normalized cDNA from 50 breast tumors
      and corresponding normal breast tissues. There was a significant reduction in
      BRMS1 mRNA expression in breast tumors compared with matched normal breast
      tissues (paired t test, P < 0.0001) and a general inverse correlation with uPA
      gene expression (P < 0.01). These results suggest that at least one of the
      underlying mechanisms of BRMS1-dependent suppression of tumor metastasis includes
      inhibition of NF-kappaB activity and subsequent suppression of uPA expression in
      breast cancer and melanoma cells.

PMID- 15867353
TI  - The p53 protein is a novel substrate of ribosomal S6 kinase 2 and a critical
      intermediary for ribosomal S6 kinase 2 and histone H3 interaction.
AB  - The tumor suppressor p53 protein is one of the most highly connected nodes in
      cellular signal transduction pathways and acts as a central regulatory switch in
      networks controlling cell proliferation and apoptosis. It is involved in the
      activation of genes that maintain control over cellular responses to DNA errors
      such as DNA repair, chromosomal recombination, and chromosome segregation. Here
      we show that ribosomal S6 kinase 2 (RSK2) activates and phosphorylates p53
      (Ser15) in vitro and in vivo and colocalizes with p53 in the nucleus. Deficiency
      of p53 diminishes RSK2-mediated phosphorylation of histone H3 (Ser10) and adding
      back p53 to p53-/- embryonic fibroblasts restored phosphorylation of histone H3
      at Ser10. These results show that the p53 protein is an important substrate of
      RSK2 and a critical intermediary in the RSK2 and histone H3 interaction. The RSK2
      p53-histone H3 complex may likely contribute to chromatin remodeling and cell
      cycle regulation.

PMID- 15867354
TI  - Degradation of human exonuclease 1b upon DNA synthesis inhibition.
AB  - In response to DNA damage, signaling pathways are triggered that either block the
      cell division cycle at defined transitions (G1-S and G2-M) or slow down
      progression through the S phase. Nucleases play important roles in DNA synthesis,
      recombination, repair, and apoptosis. In this study, we have examined the
      regulation of human exonuclease 1 (hEXO1b). The endogenous hEXO1b protein was
      only detected upon enrichment by immunoprecipitation. We found that hEXO1b was
      constantly expressed throughout the cell cycle. However, treatment of cells with
      agents that cause arrest of DNA replication led to rapid degradation of hEXO1b.
      This effect was fully reversed upon removal of the block. Analysis of
      synchronized cells showed that degradation of hEXO1b during the S phase was
      strictly dependent on DNA synthesis inhibition. DNA damage caused by UV-C
      radiation, ionizing radiation, cisplatin, or the alkylating agent N-methyl-N'
      nitro-N-nitrosoguanidine did not affect hEXO1b stability. We show that hEXO1b was
      phosphorylated in response to inhibition of DNA synthesis and that
      phosphorylation coincided with rapid protein degradation through ubiquitin
      proteasome pathways. Our data support the evidence that control of exonuclease 1
      activity may be critical for the maintenance of stalled replication forks.

PMID- 15867355
TI  - Lack of p53 Ser389 phosphorylation predisposes mice to develop 2
      acetylaminofluorene-induced bladder tumors but not ionizing radiation-induced
      lymphomas.
AB  - Cellular activity of the tumor suppressor protein p53 is primarily regulated by
      posttranslational modifications. Phosphorylation of the COOH terminus, including
      Ser389, is thought to result in a conformational change of the p53 protein,
      enhancing DNA binding and transcriptional activity. In vitro studies presented
      here show that, in addition to UV radiation, Ser389 is phosphorylated upon
      exposure to 2-acetylaminofluorene (2-AAF). Both agents induce bulky DNA adducts
      repaired by nucleotide excision repair (NER). In contrast, ionizing radiation,
      known to induce DNA damage not repaired by NER, does not result in Ser389
      phosphorylation. Previously, we have shown that p53.S389A mutant mice, lacking
      the Ser389 phosphorylation site, are sensitive to developing UV-induced skin
      tumors. Here, we show that p53.S389A mice are also prone to developing 2-AAF
      induced urinary bladder tumors, whereas no increased tumor response was found
      upon ionizing irradiation. These results provide evidence for our hypothesis that
      phosphorylation of Ser389 is important for activation of p53 to exert its
      function as a tumor suppressor not exclusively upon the presence of UV-induced
      DNA damage, but also upon exposure to other bulky adduct-inducing agents.
      Analysis of 2-AAF- and UV-induced tumors from p53.S389A mice revealed the
      presence of additional p53 mutations, indicating that lack of Ser389
      phosphorylation by itself is not sufficient to abrogate p53 function in tumor
      suppression. In addition, analyses of skin tumors of p53.S389A mice revealed an
      interesting hotspot mutation previously found exclusively in NER-deficient mice
      and patients.

PMID- 15867356
TI  - Shared epigenetic mechanisms in human and mouse gliomas inactivate expression of
      the growth suppressor SLC5A8.
AB  - Tumors arise in part from the deleterious effects of genetic and epigenetic
      mechanisms on gene expression. In several mouse models of human tumors, the
      tumorigenic phenotype is reversible, suggesting that epigenetic mechanisms also
      contribute significantly to tumorigenesis in mice. It is not known whether these
      are the same epigenetic mechanisms in human and mouse tumors or whether they
      affect homologous genes. Using an integrated approach for genome-wide methylation
      and copy number analyses, we identified SLC5A8 on chromosome 12q23.1 that was
      affected frequently by aberrant methylation in human astrocytomas and
      oligodendrogliomas. SLC5A8 encodes a sodium monocarboxylate cotransporter that
      was highly expressed in normal brain but was significant down-regulated in
      primary gliomas. Bisulfite sequencing analysis showed that the CpG island was
      unmethylated in normal brain but frequently localized methylated in brain tumors,
      consistent with the tumor-specific loss of gene expression. In glioma cell lines,
      SLC5A8 expression was also suppressed but could be reactivated with a methylation
      inhibitor. Expression of exogenous SLC5A8 in LN229 and LN443 glioma cells
      inhibited colony formation, suggesting that it may function as a growth
      suppressor in normal brain cells. Remarkably, 9 of 10 murine oligodendroglial
      tumors (from p53+/- or ink4a/arf+/- animals transgenic for S100beta-v-erbB)
      showed a similar tumor-specific down-regulation of mSLC5A8, the highly conserved
      mouse homologue. Taken together, these data suggest that SLC5A8 functions as a
      growth suppressor gene in vitro and that it is silenced frequently by epigenetic
      mechanisms in primary gliomas. The shared epigenetic inactivation of mSLC5A8 in
      mouse gliomas indicates an additional degree of commonality in the origin and/or
      pathway to tumorigenesis between primary human tumors and these mouse models of
      gliomas.

PMID- 15867357
TI  - Regulation of DNA methyltransferase 1 by the pRb/E2F1 pathway.
AB  - Tumor suppressor gene silencing by DNA hypermethylation contributes to
      tumorigenesis in many tumor types. This aberrant methylation may be due to
      increased expression and activity of DNA methyltransferases, which catalyze the
      transfer of methyl groups from S-adenosylmethionine to cytosines in CpG
      dinucleotides. Elevated expression of the maintenance DNA methyltransferase, DNA
      methyltransferase 1 (DNMT-1), has been shown in carcinomas of the colon, lung,
      liver, and prostate. Based on the nearly ubiquitous alterations of both DNA
      methylation and the retinoblastoma protein (pRb) pathway found in human cancer,
      we investigated a potential regulatory pathway linking the two alterations in
      murine and human prostate epithelial cells. Analysis of DNA methyltransferase
      levels in Rb-/- murine prostate epithelial cell lines revealed elevated Dnmt-1
      levels. Genomic DNA sequence analysis identified conserved E2F consensus binding
      sites in proximity to the transcription initiation points of murine and human
      Dnmt-1. Furthermore, the Dnmt-1 promoter was shown to be regulated by the pRb/E2F
      pathway in murine and human cell lines of epithelial and fibroblast origin. In
      the absence of pRb, Dnmt-1 transcripts exhibited aberrant cell cycle regulation
      and Rb-/- cells showed aberrant methylation of the paternally expressed gene 3
      (Peg3) tumor suppressor gene. These findings show a link between inactivation of
      the pRb pathway and induction of DNA hypermethylation of CpG island-containing
      genes in tumorigenesis.

PMID- 15867358
TI  - Disruption of Rb/E2F pathway results in increased cyclooxygenase-2 expression and
      activity in prostate epithelial cells.
AB  - The loss of the retinoblastoma tumor suppressor gene (RB) is common in many human
      cancers, including prostate. We previously reported that engineered deletion of
      RB in prostate epithelial cells results in sustained cell growth in serum-free
      media, a predisposition to develop hyperplasia and dysplasia in prostate tissue
      recombinant grafts, and sensitization to hormonal carcinogenesis. Examining the
      molecular consequence of RB loss in this system, we show that cyclooxygenase-2
      (COX-2) is significantly up-regulated following RB deletion in prostate tissue
      recombinants. To study the effect of RB deletion on COX-2 regulation, we
      generated wild-type (PrE) and Rb-/- (Rb-/-PrE) prostate epithelial cell lines
      rescued by tissue recombination. We show elevated COX-2 mRNA and protein
      expression in Rb-/-PrE cell lines with increased prostaglandin synthesis. We also
      find that loss of Rb leads to deregulated E2F activity, with increased expression
      of E2F target genes, and that exogenous expression of E2F1 results in elevated
      COX-2 mRNA and protein levels. COX-2 promoter studies reveal that E2F1
      transcriptionally activates COX-2, which is dependent on the transactivation and
      DNA-binding domains of E2F1. Further analysis revealed that the E2F1 target gene,
      c-myb, is elevated in Rb-/-PrE cells and E2F1-overexpressing cells, whereas
      ectopic overexpression of c-myb activates the COX-2 promoter in prostate
      epithelial cells. Additionally, cotransfection with E2F1 and a dominant-negative
      c-myb inhibited E2F1 activation of the COX-2 promoter. Taken together, these
      results suggest activation of a transcriptional cascade by which E2F1 regulates
      COX-2 expression through the c-myb oncogene. This study reports a novel finding
      describing that deregulation of the Rb/E2F complex results in increased COX-2
      expression and activity.

PMID- 15867359
TI  - Trimodal cancer treatment: beneficial effects of combined antiangiogenesis,
      radiation, and chemotherapy.
AB  - It has been suggested that chemotherapy and radiotherapy could favorably be
      combined with antiangiogenesis in dual anticancer strategy combinations. Here we
      investigate the effects of a trimodal strategy consisting of all three therapy
      approaches administered concurrently. We found that in vitro and in vivo, the
      antiendothelial and antitumor effects of the triple therapy combination
      consisting of SU11657 (a multitargeted small molecule inhibitor of vascular
      endothelial growth factor and platelet-derived growth factor receptor tyrosine
      kinases), Pemetrexed (a multitargeted folate antimetabolite), and ionizing
      radiation were superior to all single and dual combinations. The superior effects
      in human umbilical vein endothelial cells and tumor cells (A431) were evident in
      cell proliferation, migration, tube formation, clonogenic survival, and apoptosis
      assays (sub-G1 and caspase-3 assessment). Exploring potential effects on cell
      survival signaling, we found that radiation and chemotherapy induced endothelial
      cell Akt phosphorylation, but SU11657 could attenuate this process in vitro and
      in vivo in A431 human tumor xenografts growing s.c. on BALB/c nu/nu mice. Triple
      therapy further decreased tumor cell proliferation (Ki-67 index) and vessel count
      (CD31 staining), and induced greater tumor growth delay versus all other therapy
      regimens without increasing apparent toxicity. When testing different treatment
      schedules for the A431 tumor, we found that the regimen with radiotherapy (7.5 Gy
      single dose), given after the institution of SU11657 treatment, was more
      effective than radiotherapy preceding SU11657 treatment. Accordingly, we found
      that SU11657 markedly reduced intratumoral interstitial fluid pressure from 8.8
      +/- 2.6 to 4.2 +/- 1.5 mm Hg after 1 day. Likewise, quantitative T2-weighed
      magnetic resonance imaging measurements showed that SU11657-treated mice had
      reduced intratumoral edema. Our data indicates that inhibition of Akt signaling
      by antiangiogenic treatment with SU11657 may result in: (a) normalization of
      tumor blood vessels that cause prerequisite physiologic conditions for subsequent
      radio/chemotherapy, and (b) direct resensitization of endothelial cells to
      radio/chemotherapy. We conclude that trimodal cancer therapy combining
      antiangiogenesis, chemotherapy, and radiotherapy has beneficial molecular and
      physiologic effects to emerge as a clinically relevant antitumor strategy.

PMID- 15867360
TI  - A 27-amino-acid synthetic peptide corresponding to the NH2-terminal zinc-binding
      domain of endostatin is responsible for its antitumor activity.
AB  - The first recombinant endostatin that elicited strong antitumor activity was
      expressed in Escherichia coli and administered as a suspension. Under these
      conditions, the protein retained its full antiangiogenic activity. Lack of
      requirement for a folded structure prompted us to investigate antitumor
      properties of synthetic peptides corresponding to different regions of
      endostatin. Here, we show that the entire antitumor, antimigration, and
      antipermeability activities of endostatin are mimicked by a 27-amino-acid peptide
      corresponding to the NH2-terminal domain of endostatin. This peptide contains
      three histidines that are responsible for zinc binding. Mutations of the zinc
      binding histidines abolished its antitumor and antimigration activities, but not
      antipermeability properties.

PMID- 15867361
TI  - Neuropilin-1 suppresses tumorigenic properties in a human pancreatic
      adenocarcinoma cell line lacking neuropilin-1 coreceptors.
AB  - Neuropilin-1 (NRP-1) was first described as a coreceptor implicated in neuronal
      guidance that bound members of the semaphorin/collapsin family. NRP-1 is also
      expressed in endothelial cells and is believed to promote angiogenesis by acting
      as a coreceptor with vascular endothelial growth factor (VEGF) receptor 2. Recent
      studies suggest that NRP-1 can function through both a VEGF-dependent and VEGF
      independent fashion. Expression of NRP-1 has been shown in many human tumors,
      including pancreatic adenocarcinomas. The exact role of NRP-1 in tumor cells is
      unknown, particularly in cells that lack the NRP-1 coreceptors VEGF receptor 2
      and Plexin-A1. To discern the regulatory role(s) of NRP-1 in pancreatic
      adenocarcinoma that lack these coreceptors, we overexpressed both full-length NRP
      1 and a deletion form of NRP-1 that does not interact with semaphorin or VEGF.
      Overexpression of either isoform reduced several key tumorigenic properties,
      including anchorage-independent cell growth and migration in vitro, and resulted
      in reduced tumor incidence and tumor volume in vivo. Conversely, reduction of NRP
      1 expression by small interfering RNA targeting led to enhanced tumor growth.
      Thus, NRP-1 may play distinct growth regulatory roles in different tumor types,
      and altering NRP-1 expression or function may be a means of influencing the
      growth of pancreatic cancers.

PMID- 15867362
TI  - Farnesyltransferase inhibitors induce DNA damage via reactive oxygen species in
      human cancer cells.
AB  - Farnesyltransferase inhibitors (FTIs) possess antitumor activity. Based on recent
      findings, we hypothesized that FTIs induce reactive oxygen species (ROS) that
      damage DNA, leading to DNA damage responses. To test this hypothesis, we
      investigated the effects of FTIs on the generation of ROS, DNA double-strand
      breaks (DSB), DNA damage responses, and RhoB, and the effects of quenching ROS on
      these FTI effects. We evaluated four FTIs in human cancer cell lines of different
      tissue origins. We found that FTIs induced ROS and DSBs. Suppressing expression
      of the beta-subunit of farnesyltransferase with siRNA did not induce ROS, but
      slightly attenuated the ROS induced by FTIs. N-acetyl-L-cysteine (NAC), but not
      caspase inhibitors, blocked FTI-induced DSBs, suggesting that the DSBs were
      caused by ROS and did not result from apoptosis. The DSBs led to DNA damage
      responses. H2AX became phosphorylated and formed nuclear foci. The DNA-damage
      sensing molecules involved were probably ataxia-telangiectasia mutated protein
      (ATM) and DNA-dependent protein kinase (DNA-PK) but not ATM- and Rad3-related
      protein (ATR). Key components of the homologous recombination and nonhomologous
      end joining repair pathways (DNA-PK, BRCA1, and NBS1) underwent phosphorylation
      and formed nuclear foci. RhoB, a mediator of the antineoplastic effect of FTIs
      and a protein inducible by DNA damage, was increased by FTIs. This increase was
      blocked by NAC. We concluded that FTIs induced oxidative DNA damage by inducing
      ROS and initiated DNA damage responses, including RhoB induction, and there was a
      complex relationship among FTIs, farnesyltransferase, ROS, and RhoB. Our data
      also imply that inhibitors of DNA repair may accentuate the clinical efficacy of
      FTIs.

PMID- 15867363
TI  - RASSF1A suppresses the c-Jun-NH2-kinase pathway and inhibits cell cycle
      progression.
AB  - Some oncogenes, such as activated Ras, cause the malignant transformation of lung
      cells. c-Jun-NH2-kinase (JNK) activation is essential for the oncogenic function
      of these cells. In this study, we show that RASSF1A inhibits the growth of lung
      cancer cells by blocking the JNK pathway. The exogenous expression of RASSF1A
      suppressed JNK phosphorylation, and cells stably transfected with RASSF1A showed
      reduced JNK and c-Jun phosphorylation and Cyclin D1 down-regulation. An in vitro
      kinase assay showed that the exogenous expression of RASSF1A inhibited JNK
      activity and that JNK activity suppression due to ectopically expressed RASSF1A
      was revived by RASSF1A siRNA treatment. Based on our data, we suggest that
      RASSF1A exerts a tumor-suppressing effect by blocking oncogene-mediated JNK
      activation in lung cells.

PMID- 15867364
TI  - Both antiangiogenesis- and angiogenesis-independent effects are responsible for
      hepatocellular carcinoma growth arrest by tyrosine kinase inhibitor
      PTK787/ZK222584.
AB  - Vascular endothelial growth factor (VEGF) plays an important role in tumor
      angiogenesis of hepatocellular carcinoma. Inhibition of VEGF receptors could
      theoretically reduce angiogenesis and tumor growth in hepatocellular carcinoma,
      but this remains to be proven with an experimental study. This study examined the
      angiogenesis-dependent and angiogenesis-independent activities of PTK787/ZK222584
      (PTK787), a tyrosine kinase inhibitor of VEGF receptors, in nude mice bearing
      human hepatocellular carcinoma xenografts. The in vitro effects of PTK787 on
      proliferation, apoptosis, and cell cycle distribution in human hepatocellular
      carcinoma cell lines were also studied. Oral administration of PTK787 resulted in
      a significant reduction in tumor volume and microvessel formation of
      hepatocellular carcinoma xenografts in nude mice. PTK787 inhibited tumor cell
      proliferation in a dose-dependent manner and also induced tumor cells to undergo
      apoptosis both in vivo and in vitro. The proapoptotic response was associated
      with down-regulation of Bcl-2 and Bcl-x(L) expression and induction of cleavage
      of caspase-3. In addition, PTK787 induced growth arrest in hepatocellular
      carcinoma cells, which was associated with G1 arrest and partial G2-M block. This
      effect correlated with an increase in p21(WAF1/ CIP1) (p21) and p27KIP1 (p27)
      protein expression. In conclusion, this study showed that PTK787 is a potent
      inhibitor of tumor growth in hepatocellular carcinoma by both antiangiogenic
      effect and direct effects on tumor cell proliferation and apoptosis. Our data
      suggest that blockage of VEGF receptors may provide an effective therapeutic
      approach for human hepatocellular carcinoma.

PMID- 15867365
TI  - Estrogen receptor-binding fragment-associated antigen 9 is a tumor-promoting and
      prognostic factor for renal cell carcinoma.
AB  - The estrogen receptor-binding fragment-associated antigen 9 (EBAG9) has been
      identified as a primary estrogen-responsive gene in human breast cancer MCF7
      cells. A high expression of EBAG9 has been observed in invasive breast cancer and
      advanced prostate cancer, suggesting a tumor-promoting role of the protein in
      malignancies. Here we show that intratumoral (i.t.) administration of small
      interfering RNA against EBAG9 exerted overt regression of tumors following s.c.
      implantation of murine renal cell carcinoma (RCC) Renca cells. Overexpression of
      EBAG9 did not promote the proliferation of culture Renca cells; however, the
      inoculated Renca cells harboring EBAG9 (Renca-EBAG9) in BALB/c mice grew faster
      and developed larger tumors compared with Renca cells expressing vector alone
      (Renca-vector). After renal subcapsular implantation, Renca-EBAG9 tumors
      significantly enlarged compared with Renca-vector tumors in BALB/c mice, whereas
      both Renca-EBAG9 and Renca-vector tumors were developed with similar volumes in
      BALB/c nude mice. No apparent difference was observed in specific cytotoxic T
      cell responses against Renca-EBAG9 and Renca-vector cells; nonetheless, the
      number of infiltrating CD8+ T lymphocytes was decreased in Renca-EBAG9
      subcapsular tumors. Furthermore, immunohistochemical study of EBAG9 in 78 human
      RCC specimens showed that intense and diffuse cytoplasmic immunostaining was
      observed in 87% of the cases and positive EBAG9 immunoreactivity was closely
      correlated with poor prognosis of the patients. Multivariate analysis revealed
      that high EBAG9 expression was an independent prognostic predictor for disease
      specific survival (P = 0.0485). Our results suggest that EBAG9 is a crucial
      regulator of tumor progression and a potential prognostic marker for RCC.

PMID- 15867366
TI  - Modulation of bone microenvironment with zoledronate enhances the therapeutic
      effects of STI571 and paclitaxel against experimental bone metastasis of human
      prostate cancer.
AB  - Prostate cancer cells metastasize to the bone where their interaction with
      osteoclasts and osteoblasts can lead to alterations in the structure of the bone.
      We determined whether the systemic administration of the bisphosphonate,
      zoledronate, could prevent bone lysis and halt the proliferation of human
      prostate cancer cells injected into the tibia of nude mice. Zoledronate did not
      affect the in vitro proliferation of human prostate cancer PC-3MM2 cells. The in
      vivo administration of zoledronate produced significant bone preservation but did
      not inhibit the progressive growth of PC-3MM2 cells. The systemic administration
      of STI571 (imatinib mesylate, Gleevec), an inhibitor of phosphorylation of the
      platelet-derived growth factor receptor, in combination with paclitaxel, produced
      apoptosis of tumor cells and bone- and tumor-associated endothelial cells. The
      systemic administration of zoledronate with STI571 and paclitaxel produced a
      significant preservation of bone structure, a decrease in tumor incidence and
      weight, and a decrease in incidence of lymph node metastasis. This therapeutic
      activity was correlated with inhibition of osteoclast function, inhibition of
      tumor cell proliferation, and induction of apoptosis in tumor-associated
      endothelial cells and tumor cells. Cancer is a heterogeneous disease that
      requires multimodality therapy. The present data recommend the combination of a
      bisphosphonate agent with protein tyrosine kinase inhibitor and an anticycling
      drug for the treatment of prostate cancer bone metastasis.

PMID- 15867367
TI  - Dual inhibition of epidermal growth factor receptor and vascular endothelial
      growth factor receptor phosphorylation by AEE788 reduces growth and metastasis of
      human colon carcinoma in an orthotopic nude mouse model.
AB  - We studied growth factors and their receptors in tumor cells and tumor-associated
      endothelial cells as the therapeutic targets in colon cancer. Immunohistochemical
      analysis of 13 surgical specimens of human colon adenocarcinoma revealed that
      both tumor cells and tumor-associated endothelial cells in 11 of the 13 specimens
      expressed the epidermal growth factor (EGF), transforming growth factor alpha
      (TGF-alpha), EGF receptor (EGFR), phosphorylated EGFR (pEGFR), vascular
      endothelial growth factor (VEGF), VEGF receptor (VEGFR), and phosphorylated VEGFR
      (pVEGFR). HT29 human colon cancer cells growing orthotopically in the cecum of
      nude mice expressed a high level of EGF, EGFR, pEGFR, VEGF, VEGFR, and pVEGFR.
      Double-immunofluorescence staining found that tumor-associated mouse endothelial
      cells also expressed pEGFR and pVEGFR. Tumors in mice treated for 5 weeks with
      oral AEE788 (an inhibitor of EGFR and VEGFR tyrosine kinase) as a single agent or
      with CPT-11 alone were smaller (>50%) than those in control mice. Mice treated
      with the combination of AEE788 and CPT-11 had significantly smaller tumors (P <
      0.01) and complete inhibition of lymph node metastasis. AEE788 alone or in
      combination with CPT-11 inhibited pEGFR, pVEGFR, and phosphorylated Akt
      expression on tumor-associated endothelial cells as well as on tumor cells. The
      combination therapy also significantly decreased microvessel density and tumor
      cell proliferation and increased the level of apoptosis in both tumor cells and
      tumor-associated endothelial cells. Collectively, these data suggest that the
      dual inhibition of EGFR and VEGFR signaling pathways in tumor cells and tumor
      associated endothelial cells in combination with chemotherapy can provide a new
      approach to the treatment of colon cancer.

PMID- 15867368
TI  - Overexpression of cytochrome P450 1A1 and its novel spliced variant in ovarian
      cancer cells: alternative subcellular enzyme compartmentation may contribute to
      carcinogenesis.
AB  - Epithelial ovarian cancer derived from the human ovarian surface epithelium
      (HOSE) is the leading cause of death from gynecologic malignancies among American
      women. Metabolic activation of endogenous and exogenous chemicals by cytochrome
      P450 (CYP) class I enzymes has been implicated in its etiology. In this study, we
      showed overexpression of CYP1A1 mRNA, but not CYP1B1 transcripts, in ovarian
      cancer cell lines when compared with primary cultures or immortalized HOSE cell
      lines. Importantly, we identified a novel, enzymatically active, spliced variant
      of CYP1A1 (CYP1A1v) formed by excision of an 84-bp cryptic intron in exon 2.
      CYP1A1v is overexpressed in ovarian cancer cell lines and exhibits a unique
      subcellular distribution restricted to the nucleus and mitochondria, contrary to
      the endoplasmic reticulum localization of the wild-type enzyme. In concordance,
      total CYP1A1 activity, as measured by the ethoxyresorufin O-deethylase assay, was
      detected in mitochondrial, nuclear, and microsomal fractions of ovarian cancer
      cells but was notably absent in all subcellular fractions of HOSE cells.
      Immunocytochemistry studies in 30 clinical specimens revealed overexpression of
      CYP1A1 in various types of ovarian cancers compared with benign epithelia and
      frequent localization of the enzyme to cancer cell nuclei. Forced expression of
      CYP1A1wt or CYP1A1v in HOSE cells resulted in nuclear localization of the enzyme
      and acquisition of anchorage-independent growth, which was further exacerbated
      following exposure to benzo(a)pyrene or 17beta-estradiol. Collectively, these
      data provided the first evidence that CYP1A1 overexpression and alternative
      splicing could contribute to ovarian cancer initiation and progression.

PMID- 15867370
TI  - p53 translocation to mitochondria precedes its nuclear translocation and targets
      mitochondrial oxidative defense protein-manganese superoxide dismutase.
AB  - The tumor suppressor gene p53 is activated by reactive oxygen species-generating
      agents. After activation, p53 migrates to mitochondria and nucleus, a response
      that eventually leads to apoptosis, but how the two events are related is
      unknown. Herein, we show that p53 translocation to mitochondria precedes its
      translocation to nucleus in JB6 skin epidermal cells treated with the tumor
      promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Translocation of p53 to
      mitochondria occurs within 10 minutes after TPA application. In the mitochondria,
      p53 interacts with the primary antioxidant enzyme, manganese superoxide dismutase
      (MnSOD), consistent with the reduction of its superoxide scavenging activity, and
      a subsequent decrease of mitochondrial membrane potential. In contrast to the
      immediate action on mitochondria, p53 transcriptional activity in the nucleus
      increases at 1 hour following TPA application, accompanied by an increase in the
      levels of its target gene bax at 15 hours following TPA treatment. Activation of
      p53 transcriptional activity is preventable by application of a SOD mimetic (MnTE
      2-PyP5+). Thus, p53 translocation to mitochondria and subsequent inactivation of
      MnSOD explains the observed mitochondrial dysfunction, which leads to
      transcription-dependent mechanisms of p53-induced apoptosis.

PMID- 15867369
TI  - Cyclooxygenase-1 is a potential target for prevention and treatment of ovarian
      epithelial cancer.
AB  - The precise genetic and molecular defects underlying epithelial ovarian cancer
      (EOC) remain largely unknown, and treatment options for patients with advanced
      disease are limited. Cyclooxygenases (COX-1 and COX-2) catalyze the conversion of
      arachidonic acid to prostaglandins. Whereas overwhelming evidence suggests a role
      for COX-2 in a variety of cancers, the contribution of COX-1 remains much less
      explored. The expression status of COX isoforms in ovarian cancers also remains
      confusing. We have previously shown that human epithelial ovarian tumors have
      increased levels of COX-1 but not COX-2. To more carefully examine the role of
      COXs in ovarian cancer, we used a mouse model of EOC in which genetic and
      oncogenic modifications were experimentally engineered into ovarian surface
      epithelial cells (OSE) thought to be the cells of origin for human EOC. These OSE
      cells produce tumors when allografted into host mice. Using multiple approaches,
      we observed that OSE cells and the tumors comprised of these cells express high
      levels of COX-1 but not COX-2. Prostacyclin (PGI(2)) is the major prostaglandin
      generated downstream of COX-1 in these cells, and SC-560, a COX-1-selective
      inhibitor, dramatically inhibits PGI(2) production. More importantly, SC-560
      reduced the growth of tumors when OSE cells were allografted in nude female mice.
      In contrast, the COX-2-selective inhibitor celecoxib had little effect on tumor
      growth. The growth inhibitory effects of SC-560 result from reduced cell
      proliferation and/or accelerated apoptosis. Our results imply COX-1 as a target
      for the prevention and/or treatment of EOC.

PMID- 15867371
TI  - Proapoptotic activity of new glutathione S-transferase inhibitors.
AB  - Selected 7-nitro-2,1,3-benzoxadiazole derivatives have been recently found very
      efficient inhibitors of glutathione S-transferase (GST) P1-1, an enzyme which
      displays antiapoptotic activity and is also involved in the cellular resistance
      to anticancer drugs. These new inhibitors are not tripeptide glutathione
      peptidomimetic molecules and display lipophylic properties suitable for crossing
      the plasma membrane. In the present work, we show the strong cytotoxic activity
      of these compounds in the following four different cell lines: K562 (human
      myeloid leukemia), HepG2 (human hepatic carcinoma), CCRF-CEM (human T
      lymphoblastic leukemia), and GLC-4 (human small cell lung carcinoma). The LC50
      values are in the micromolar/submicromolar range and are close to the IC50 values
      obtained with GSTP1-1, suggesting that the target of these molecules inside the
      cell is indeed this enzyme. The cytotoxic mechanism of 6-(7-nitro-2,1,3
      benzoxadiazol-4-ylthio)hexanol, the most effective GSTP1-1 inhibitor, has been
      carefully investigated in leukemic CCRF-CEM and K562 cell lines. Western blot and
      immunoprecipitation analyzes have shown that 6-(7-nitro-2,1,3-benzoxadiazol-4
      ylthio)hexanol promotes in both cell lines the dissociation of the GSTP1-1 in a
      complex with c-jun NH2-terminal kinase (JNK). This process triggers a reactive
      oxygen species (ROS)-independent activation of the JNK-mediated pathway that
      results in a typical process of apoptosis. Besides this main pathway, in K562
      cells, a ROS-mediated apoptosis partially occurs (about 30%) which involves the
      p38MAPK signal transduction pathway. The low concentration of this new compound
      needed to trigger cytotoxic effects on tumor cells and the low toxicity on mice
      indicate that the new 7-nitro-2,1,3-benzoxadiazole derivatives are promising
      anticancer agents.

PMID- 15867372
TI  - Glyceraldehyde-3-phosphate dehydrogenase binds to the AU-Rich 3' untranslated
      region of colony-stimulating factor-1 (CSF-1) messenger RNA in human ovarian
      cancer cells: possible role in CSF-1 posttranscriptional regulation and tumor
      phenotype.
AB  - The overexpression of the colony-stimulating factor-1(CSF-1) by epithelial
      ovarian cancer cells enhances invasiveness and metastatic properties,
      contributing to the poor prognosis of the patients. It has been suggested that
      CSF-1 3' untranslated region containing AU-rich elements (ARE) could regulate CSF
      1 posttranscriptional expression and be responsible for its aberrant abundance in
      such cancer cells. In this study, normal (NOSE.1) and malignant (Hey) ovarian
      epithelial cells were used to examine CSF-1 expression and regulation. CSF-1
      overexpression in Hey cells was found to associate with increased invasiveness,
      motility, urokinase activity, and virulence of tumorigenicity, compared with
      NOSE.1 cells, which expressed little CSF-1. CSF-1 ARE was further found to serve
      as an mRNA decay element that correlates with down-regulation of protein
      translation. Moreover, such down-regulation was found more prominent in NOSE.1
      than in Hey cells, suggesting differences in posttranscriptional regulation. As a
      variety of trans-acting factors [AU-binding protein (AUBP)] are known to modulate
      messenger stability through binding to such elements, we examined the protein
      content of both cell lines for their ability to bind the CSF-1 ARE. Our results
      strongly suggested the abundance of such AUBP activity in Hey cells. We isolated
      a 37-kDa AUBP, which was identified as glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH). To summarize, our study identified GAPDH as an AUBP abundant in Hey
      cells, where it binds to CSF-1 ARE that imparts mRNA decay. These data suggest
      that GAPDH binding to CSF-1 ARE sequence prevents CSF-1 mRNA decay and subsequent
      down-regulation of CSF-1 protein translation, leading to CSF-1 overexpression and
      increased metastatic properties seen in ovarian cancer.

PMID- 15867373
TI  - Suppression of tumor development and metastasis formation in mice lacking the
      S100A4(mts1) gene.
AB  - The S100A4(mts1) protein stimulates metastatic spread of tumor cells. An elevated
      expression of S100A4 is associated with poor prognosis in many human cancers.
      Dynamics of tumor development were studied in S100A4-deficient mice using grafts
      of CSML100, highly metastatic mouse mammary carcinoma cells. A significant delay
      in tumor uptake and decreased tumor incidences were observed in S100A4(-/-) mice
      compared with the wild-type controls. Moreover, tumors developed in S100A4(-/-)
      mice never metastasize. Immunohistochemical analyses of these tumors revealed
      reduced vascularity and abnormal distribution of host-derived stroma cells.
      Coinjection of CSML100 cells with immortalized S100A4(+/+) fibroblasts partially
      restored the dynamics of tumor development and the ability to form metastasis.
      These fibroblasts were characterized by an enhanced motility and invasiveness in
      comparison with S100A4(-/-) fibroblasts, as well as by the ability to release
      S100A4 into the tumor environment. Taken together, our results point to a
      determinative role of host-derived stroma cells expressing S100A4 in tumor
      progression and metastasis.

PMID- 15867374
TI  - Tumor development by transgenic expression of a constitutively active insulin
      like growth factor I receptor.
AB  - The insulin-like growth factor I receptor (IGF-IR) is a transmembrane tyrosine
      kinase that is essential to growth and development and also thought to provide a
      survival signal for the maintenance of the transformed phenotype. There has been
      increasing interest in further understanding the role of IGF-I signaling in
      cancer and in developing receptor antagonists for therapeutic application. We
      describe herein a novel animal model that involves transgenic expression of a
      fusion receptor that is constitutively activated by homodimerization. Transgenic
      mice that expressed the activated receptor showed aberrant development of the
      mammary glands and developed salivary and mammary adenocarcinomas as early as 8
      weeks of age. Xenograft tumors and a cell line were derived from the transgenic
      animals and are sensitive to inhibition by a novel small-molecule inhibitor of
      the IGF-IR kinase. This new model should provide new opportunities for further
      understanding how aberrant IGF-IR signaling leads to tumorigenesis and for
      optimizing novel antagonists of the receptor kinase.

PMID- 15867375
TI  - The G protein-coupled receptor S1P2 regulates Rho/Rho kinase pathway to inhibit
      tumor cell migration.
AB  - Sphingosine 1-phosphate (S1P) is a lysophospholipid that exerts a variety of
      responses in cells such as proliferation, migration, and survival. These effects
      are mediated by G protein-coupled receptors on the cell surface (S1P1-5), which
      activate downstream signaling intermediates such as Rac and Rho GTPases.
      Mechanisms of S1P action in human glioblastoma cells are not well defined. S1P
      receptors (1-5) and S1P-metabolizing enzymes were expressed in three human
      glioblastoma cell lines. S1P had a profound and differential effect on
      glioblastoma cell migration. U87 cells treated with S1P showed a significant
      increase in migration, whereas U118 and U138 cell lines were strongly inhibited.
      S1P-mediated inhibition correlated with S1P2 receptor expression. FTY720-P, an
      S1P analogue that binds all S1P receptors except S1P2, did not inhibit
      glioblastoma cell migration. Overexpression of S1P2 further suppressed migration,
      and blockage of S1P2 mRNA expression by small interfering RNA reversed the
      inhibitory effect. Contrary to previous reports showing bimodal regulation of Rac
      activity and migration by S1P2 receptor stimulation, both Rac1 and RhoA GTPases
      were activated by S1P treatment in native cells and cells overexpressing S1P2.
      Treatment of U118 cells with the Rho-associated protein kinase (ROCK) inhibitor Y
      27632 restored migration suggesting that ROCK-dependent mechanisms are important.
      Actin staining of S1P stimulated U118 cells overexpressing beta-galactosidase
      resulted in pronounced stress fiber formation that was exacerbated by S1P2
      overexpression, partially blocked by S1P1, or totally abolished by pretreatment
      with Y-27632. These data provide evidence of a novel mechanism of S1P inhibition
      of tumor cell migration via Rho kinase-dependent pathway.

PMID- 15867376
TI  - Human homologue of cement gland protein, a novel metastasis inducer associated
      with breast carcinomas.
AB  - A suppression subtractive cDNA library representing mRNAs expressed at a higher
      level in the malignant human breast cancer cell line, MCF-7, relative to a benign
      breast tumor-derived cell line, Huma 123, contained a cDNA, M36, which was
      expressed in estrogen receptor alpha (ERalpha)-positive breast carcinoma cell
      lines but not in cell lines from normal/benign/ERalpha-negative malignant breast
      lesions. M36 cDNA had an identical coding sequence to anterior gradient 2 (AGR2),
      the human homologue of the cement gland-specific gene (Xenopus laevis). Screening
      of breast tumor specimens using reverse transcription-PCR and immunocytochemistry
      with affinity-purified anti-AGR2 antibodies showed that the presence of AGR2 mRNA
      and protein were both statistically significantly associated with ERalpha
      positive carcinomas (P = 0.007, Fisher's exact test) and with malignancy (P < or
      = 0.025). When an expression vector for AGR2 cDNA was introduced into benign
      nonmetastatic rat mammary tumor cells, and three separate clones and two pools of
      cells were transferred to the mammary glands of syngeneic hosts, there were no
      consistent differences in the mean latent periods of tumor formation. However,
      metastases occurred in the lungs of animals receiving the AGR2 transfectants in
      77% to 92% of animals with primary tumors (P = 0.0001) compared with no
      metastases in the control groups. The AGR2 transfectants exhibited enhanced rates
      of adhesion to a plastic substratum and extracellular AGR2 enhanced the rate of
      attachment of AGR2-negative but not AGR2-positive cells. These experiments are
      the first to link mechanistically the developmental gene product, AGR2, with
      metastasis in vivo.

PMID- 15867377
TI  - Identification of the ubiquitin-proteasome pathway in the regulation of the
      stability of eukaryotic elongation factor-2 kinase.
AB  - Eukaryotic elongation factor-2 kinase (eEF-2 kinase) is a highly conserved
      calcium/calmodulin-dependent enzyme involved in the regulation of protein
      translation and cell proliferation. Rapid changes in the activity and abundance
      of eEF-2 kinase have been observed on growth stimulation, and increased enzyme
      activity is characteristic of malignant cell growth. Yet the mechanism for
      controlling the turnover of this kinase is unknown. The ubiquitin-proteasome
      pathway regulates the degradation of many cellular proteins, including
      transcription factors, cell cycle regulators, and signal transduction proteins.
      Therefore, we determined whether the ubiquitin-proteasome pathway regulates the
      turnover of eEF-2 kinase. We found that eEF-2 kinase was a relatively short-lived
      protein with a half-life of less than 6 hours. eEF-2 kinase was ubiquitinated in
      vivo as determined by coimmunoprecipitation and polyubiquitin affinity matrix.
      Incubation of purified eEF-2 kinase with a source of ubiquitination enzymes
      (rabbit reticulocyte lysate), purified ubiquitin, and ATP revealed the presence
      of increasing molecular weight species of ubiquitinated eEF-2 kinase. Treatment
      of cells with MG132, a proteasome inhibitor, inhibited eEF-2 kinase degradation
      and induced the accumulation of polyubiquitinated forms of the enzyme, resulting
      in an increase in its half-life. These results suggest involvement of the
      proteasome in the turnover of the ubiquitinated kinase. Because eEF-2 kinase is
      chaperoned by heat shock protein 90 (Hsp90), we next determined if disruption of
      the Hsp90-eEF-2 kinase complex promoted degradation of the kinase. Treatment of
      cells with geldanamycin, an Hsp90 inhibitor, enhanced ubiquitination of eEF-2
      kinase and decreased the half-life of the kinase to less than 2 hours. These
      results indicate that cellular levels of eEF-2 kinase are maintained by a balance
      between association with Hsp90 and degradation by the ubiquitin-proteasome
      pathway. In conclusion, these data show that the turnover of eEF-2 kinase is
      regulated by the ubiquitin-proteasome pathway and, therefore, modulating the
      ubiquitination of eEF-2 kinase might control the abundance of this enzyme and
      have implications in the treatment of certain forms of cancer.

PMID- 15867378
TI  - Impairment of stromelysin-1 transcriptional activity by promoter mutations in
      high microsatellite instability colorectal tumors.
AB  - Colorectal tumorigenesis is characterized by the sequential inactivation of a
      series of tumor suppressor genes (microsatellite-stable tumors) and genetic or
      epigenetic alterations in mismatch repair genes in nonpoliposic hereditary
      tumours and 13% to 15% of sporadic colorectal cancer [high microsatellite
      instability (MSI-H) tumors]. We hypothesized a molecular mechanism for MSI-H
      colorectal tumors related to matrix metalloproteinase 3 (MMP-3) promoter
      mutations, down-regulation of MMP-3 expression, and impairment of MMP-9
      activation. We have now analyzed the 2.2-kb full MMP-3 promoter to assess the
      mutation distribution. The mutations found are restricted to the polymorphic
      region that includes the zinc-binding protein (ZBP-89) binding element. To show
      that these alterations were the cause of the low expression of this gene, we have
      generated three constructs with different MMP-3 promoters (wild type and two
      mutants) and we have expressed them in SW480 human colorectal cells. The basal
      transcriptional activity of wild-type MMP-3 promoter was much higher than the
      mutants activity. In addition, 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced
      transcriptional activity of wild-type MMP-3 promoter was 10-fold higher than the
      mutants activity. Dexamethasone inhibited the basal transcriptional activity of
      wild-type MMP-3 promoter and of the two mutants found in the MSI-H subgroup of
      colorectal tumors. Significantly, dexamethasone almost completely blunted the TPA
      induced effect on wild-type MMP-3 promoter transcriptional activity and on the
      mutants, even below their basal activity. Our data show that mutations found in
      the polymorphic region of the MMP-3 promoter from MSI-H colorectal tumors impair
      its basal and induced transcriptional activity, which may contribute to their
      better clinical outcome.

PMID- 15867379
TI  - Valproic acid alters chromatin structure by regulation of chromatin modulation
      proteins.
AB  - Histone acetylation and deacetylation are crucial in the regulation of gene
      expression. Dynamic changes in gene expression may affect chromatin structure
      and, consequently, the interaction of chromatin with regulatory factors. In this
      study, the effects of the antiseizure drug valproic acid (VPA) on the expression
      of genes that regulate the structure of chromatin and the access of
      macromolecules to the DNA were investigated. Exposure of breast cancer cells to
      VPA resulted in rapid dose-dependent hyperacetylation of the histones H3 and H4.
      VPA further induced a depletion of several members of the structural maintenance
      of chromatin (SMC) proteins, SMC-associated proteins, DNA methyltransferase, and
      heterochromatin proteins. Down-regulation of these proteins was associated with
      chromatin decondensation. The observed alterations of chromatin structure
      correlated with enhanced sensitivity of DNA to nucleases and increased
      interaction of DNA with intercalating agents. VPA-induced chromatin
      decondensation led to a sequence-specific potentiation of DNA-damaging agents in
      cell culture and xenograft models. Modulation of heterochromatin maintenance
      proteins was not a direct, but a downstream, effect of histone acetylation. The
      effects on the chromatin structure were reversible upon drug withdrawal, but
      obligatory for the potentiation of DNA-damaging agents. In addition to their
      antitumor activity as single agents, the chromatin decondensation induced by
      histone deacetylase inhibitors may enhance the efficacy of cytotoxic agents that
      act by targeting DNA. The proposed mechanism of action suggests an effect of drug
      sequencing on the antitumor activity of these drugs.

PMID- 15867380
TI  - Mouse models of subcutaneous spleen reservoir for multiple portal venous
      injections to treat liver malignancies.
AB  - Dog and rat animal models have been developed for repeated intravascular
      administrations to the liver. However, mice have generally been considered too
      small to use for these models. This study describes the development of mouse
      models that permit the establishment of liver metastases that can be subsequently
      treated by repeated injections into the portal venous system. A mini-laparotomy
      is done to mobilize the spleen and transpose it to a s.c. pocket with its
      vascular pedicle intact. A suspension of single tumor cells is then inoculated
      into the portal vein to establish diffuse liver metastases. These tumors may be
      treated by simple percutaneous injections directly into the s.c. whole spleen
      reservoir. The ease of injection into the s.c. spleen permits repeated injections
      into the portal venous system. The usefulness of this model was shown in
      experiments revealing that multiple portal venous administrations of a
      replication-conditional, oncolytic herpes simplex virus mutant are more effective
      than a single portal venous administration. In a modification of this model, the
      spleen is first split into two, leaving intact the vascular pedicle for each half
      of the spleen. Tumor cells are inoculated into one hemi-spleen, which is then
      resected 10 minutes later. The other hemi-spleen is transposed to the s.c.
      position, thereby permitting subsequent repetitive portal venous injections via
      percutaneous injections into the s.c. hemi-spleen. These mouse models are useful
      for a wide range of studies.

PMID- 15867381
TI  - Mitochondrial-mediated disregulation of Ca2+ is a critical determinant of Velcade
      (PS-341/bortezomib) cytotoxicity in myeloma cell lines.
AB  - The proteasome inhibitor bortezomib (also known as PS-341/Velcade) is a
      dipeptidyl boronic acid that has recently been approved for use in patients with
      multiple myeloma. Bortezomib inhibits the activity of the 26S proteasome and
      induces cell death in a variety of tumor cells; however, the mechanism of
      cytotoxicity is not well understood. In this report, oligonucleotide microarray
      analysis of the 8226 multiple myeloma cell line showed a predominant induction of
      gene products associated with the endoplasmic reticulum secretory pathway
      following short-term, high-dose exposure to bortezomib. Examination of mediators
      of endoplasmic reticulum stress-induced cell death showed specific activation of
      caspase 12, as well as of caspases 8, 9, 7, and 3, and cleavage of bid. Treatment
      of myeloma cells with bortezomib also showed disregulation of intracellular Ca2+
      as a mechanism of caspase activation. Cotreatment with a panel of Ca2+-modulating
      agents identified the mitochondrial uniporter as a critical regulatory factor in
      bortezomib cytotoxicity. The uniporter inhibitors ruthenium red and Ru360
      prevented caspase activation and bid cleavage, and almost entirely inhibited
      bortezomib-induced cell death, but had no effect on any other chemotherapeutic
      drug examined. Additional Ca2+-modulating agents, including 2-amino
      ethoxydiphenylborate, 1,2-bis (o-aminophenoxy) ethane-tretraacetic acid
      (acetoxymethyl) ester, and dantrolene, did not alter bortezomib cytotoxicity.
      Analysis of intracellular Ca2+ showed that the ruthenium-containing compounds
      inhibited Ca2+ store loading and abrogated the desensitized capacitative calcium
      influx associated with bortezomib treatment. These data support the hypothesis
      that intracellular Ca2+ disregulation is a critical determinant of bortezomib
      cytotoxicity.

PMID- 15867382
TI  - Motexafin gadolinium disrupts zinc metabolism in human cancer cell lines.
AB  - To gain a better understanding of the mechanism of action of the metal cation
      containing chemotherapeutic drug motexafin gadolinium (MGd), gene expression
      profiling analyses were conducted on plateau phase human lung cancer (A549) cell
      cultures treated with MGd. Drug treatment elicited a highly specific response
      that manifested in elevated levels of metallothionein isoform and zinc
      transporter 1 (ZnT1) transcripts. A549 cultures incubated with MGd in the
      presence of exogenous zinc acetate displayed synergistic increases in the levels
      of intracellular free zinc, metallothionein transcripts, inhibition of
      thioredoxin reductase activity, and cell death. Similar effects were observed in
      PC3 prostate cancer and Ramos B-cell lymphoma cell lines. Intracellular free zinc
      levels increased in response to treatment with MGd in the absence of exogenous
      zinc, indicating that MGd can mobilize bound intracellular zinc. These findings
      lead us to suggest that an important component of the anticancer activity of MGd
      is related to its ability to disrupt zinc metabolism and alter cellular
      availability of zinc. This class of compounds may provide insight into the
      development of novel cancer drugs targeting control of intracellular free zinc
      and the roles that zinc and other metal cations play in biochemical pathways
      relevant to cancer.

PMID- 15867383
TI  - Cooperation between Cdk4 and p27kip1 in tumor development: a preclinical model to
      evaluate cell cycle inhibitors with therapeutic activity.
AB  - Deregulation of the G1-S transition of the cell cycle is a common feature of
      human cancer. Tumor-associated alterations in this process frequently affect
      cyclin-dependent kinases (Cdk), their regulators (cyclins, INK4 inhibitors, or
      p27Kip1), and their substrates (retinoblastoma protein). Although these proteins
      are generally thought to act in a linear pathway, mutations in different
      components frequently cooperate in tumor development. Using gene-targeted mouse
      models, we report in this article that Cdk4 resistance to INK4 inhibitors, due to
      the Cdk4 R24C mutation, strongly cooperates with p27(Kip1) deficiency in tumor
      development. No such cooperation is observed between Cdk4 R24C and p18(INK4c)
      absence, suggesting that the only function of p18INK4c is inhibiting Cdk4 in this
      model. Cdk4(R/R) knock in mice, which express the Cdk4 R24C mutant protein,
      develop pituitary tumors with complete penetrance and short latency in a p27Kip1
      /- or p27Kip1+/- background. We have investigated whether this tumor model could
      be useful to assess the therapeutic activity of cell cycle inhibitors. We show
      here that exposure to flavopiridol, a wide-spectrum Cdk inhibitor, significantly
      delays tumor progression and leads to tumor-free survival in a significant
      percentage of treated mice. These data suggest that genetically engineered tumor
      models involving key cell cycle regulators are a valuable tool to evaluate drugs
      with potential therapeutic benefit in human cancer.

PMID- 15867384
TI  - Supra-additive growth inhibition by a celecoxib analogue and carboxyamido
      triazole is primarily mediated through apoptosis.
AB  - Combination studies of celecoxib and chemotherapeutic agents suggest that
      combining cyclooxygenase-2 inhibitors with other agents may have supra-additive
      or synergistic effects on tumor growth inhibition. Carboxyamido-triazole (CAI), a
      voltage-independent calcium channel inhibitor, has been shown to induce growth
      inhibition and apoptosis in cancer cells. We found that continuous exposure to
      cytostatic doses of CAI and LM-1685, a celecoxib analogue, reduced the
      proliferation and survival of seven human cancer cell lines by at least one log
      (P < or = 0.001) over either agent alone. To explore the mechanism of action of
      this combination, we further studied the effects of LM-1685/CAI on CCL-250
      colorectal carcinoma cells. We found that the supra-additive antiproliferative
      effects occurred throughout a range of LM-1685 doses (5-25 micromol/L) and
      paralleled a decrease in COX-2 activity as measured by prostaglandin E2
      production. In these cells, treatment with LM-1685/CAI suppressed the
      extracellular signal-regulated kinase pathway within the first hour but
      ultimately results in high, sustained activation of ERK over a 9-day period (P =
      0.0005). Suppression of cyclin D1 and phospho-AKT, and cleavage of caspase-3 and
      PARP were concomitant with persistent ERK activation. Addition of PD98059, a MEK
      1 inhibitor, suppressed ERK activation and significantly but incompletely
      reversed these signaling events and apoptosis. Flow cytometry experiments
      revealed that the CAI/LM-1685 combination induced a 3-fold increase in apoptosis
      over control (P = 0.005) in 3 days. We show that the combination of CAI and LM
      1685 produces a cytotoxic effect by suppressing proliferation and triggering
      apoptosis.

PMID- 15867385
TI  - Glucosylceramide synthase blockade down-regulates P-glycoprotein and resensitizes
      multidrug-resistant breast cancer cells to anticancer drugs.
AB  - Overexpression of glucosylceramide synthase (GCS), a pivotal enzyme in glycolipid
      biosynthesis, contributes to cancer cell resistance to chemotherapy. We
      previously showed that transfection of doxorubicin-resistant MCF-7-AdrR cells
      with GCS antisense restored cell sensitivity to doxorubicin and greatly enhanced
      sensitivity to vinblastine and paclitaxel. In that study, doxorubicin promoted
      generation of ceramide in MCF-7-AdrR/GCS antisense cells; the present study
      implicates factors in addition to ceramide that augment sensitivity to
      chemotherapy. Although GCS antisense cells showed enhanced ceramide formation
      compared with MCF-7-AdrR when challenged with paclitaxel, GCS antisense cells
      also showed a 10-fold increase in levels of intracellular drug (paclitaxel and
      vinblastine). In addition, transfected cells had dramatically decreased
      expression (80%) of P-glycoprotein and a 4-fold decrease in the level of cellular
      gangliosides. Chemical inhibition of GCS produced the same effects as antisense
      transfection: exposure of MCF-7-AdrR cells to the GCS inhibitor 1-phenyl-2
      palmitoylamino-3-morpholino-1-propanol (PPMP, 5.0 micromol/L, 4 days) decreased
      ganglioside levels, restored sensitivity to vinblastine, enhanced vinblastine
      uptake 3-fold, and diminished expression of MDR1 by 58%, compared with untreated
      controls. A similar effect was shown in vinblastin-resistant KB-V0.01 cells;
      after 7 days with PPMP (10 micromol/L), MDR1 expression fell by 84% and P
      glycoprotein protein levels decreased by 50%. MCF-7-AdrR cells treated with small
      interfering RNAs to specifically block GCS also showed a dramatic decrease in
      MDR1 expression. This work shows that limiting GCS activity down-regulates the
      expression of MDR1, a phenomenon that may drive the chemosensitization associated
      with blocking ceramide metabolism. The data suggest that lipids play a role in
      the expression of multidrug resistance.

PMID- 15867386
TI  - Antitumor activity of the insulin-like growth factor-I receptor kinase inhibitor
      NVP-AEW541 in musculoskeletal tumors.
AB  - Identification of new drugs is strongly needed for sarcomas. Insulin-like growth
      factor-I receptor (IGF-IR) was found to provide a major contribution to the
      malignant behavior of these tumors, therefore representing a very promising
      therapeutic target. In this study, we analyzed the therapeutic potential of a
      novel kinase inhibitor of IGF-IR, NVP-AEW541, in Ewing's sarcoma, osteosarcoma,
      and rhabdomyosarcoma, the three most frequent solid tumors in children and
      adolescents. NVP-AEW541 inhibits IGF-I-mediated receptor activation and
      downstream signaling. Ewing's sarcoma cells were generally found to be more
      sensitive to the effects of this drug compared with rhabdomyosarcoma and
      osteosarcoma, in agreement with the high dependency of this neoplasm to IGF-IR
      signaling. NVP-AEW541 induced a G1 cell cycle block in all cells tested, whereas
      apoptosis was observed only in those cells that show a high level of sensitivity.
      Concurrent exposure of cells to NVP-AEW541 and other chemotherapeutic agents
      resulted in positive interactions with vincristine, actinomycin D, and ifosfamide
      and subadditive effects with doxorubicin and cisplatin. Accordingly, combined
      treatment with NVP-AEW541 and vincristine significantly inhibited tumor growth of
      Ewing's sarcoma xenografts in nude mice. Therefore, results encourage inclusion
      of this drug especially in the treatment of patients with Ewing's sarcoma. For
      the broadest applicability and best efficacy in sarcomas, NVP-AEW541 may be
      combined with vincristine, actinomycin D, and ifosfamide, three major drugs in
      the treatment of sarcomas.

PMID- 15867387
TI  - Epidermal growth factor receptor-related protein inhibits cell growth and induces
      apoptosis of BxPC3 pancreatic cancer cells.
AB  - Dysregulation of the epidermal growth factor receptor (EGFR) signaling network
      has been frequently reported in pancreatic cancer. Inhibition of EGFR was
      associated with antitumor effects in both in vitro and in vivo studies of
      pancreatic cancer. We have previously reported the isolation and characterization
      of an EGFR-related protein (ERRP), which seems to be a negative regulator of
      EGFR. In the present investigation, we tested our hypothesis whether recombinant
      ERRP could be an effective inhibitor of growth of BxPC3 pancreatic cancer cells.
      Cell growth and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide and apoptosis ELISA assay, respectively, in the
      presence and absence of recombinant ERRP in BxPC3 cells. To evaluate activation
      of EGFR and its downstream signaling events, levels of phospho-EGFR, phospho-AKT,
      and phospho-extracellular signal-regulated kinase (phospho-ERK) were determined
      by Western blot analysis. NF-kappaB activity was measured by electrophoretic
      mobility shift assay. Our data show, for the first time, that ERRP inhibits the
      growth of BxPC3 cells in a dose- and time-dependent manner. The EGF or
      transforming growth factor (TGF)-alpha-induced stimulation of cell growth and
      activation of EGFR was also inhibited by ERRP. These changes were accompanied by
      a concomitant attenuation of activation of mitogen-activated protein (MAP)
      kinases, AKT, and NF-kappaB. ERRP also induced apoptosis as evidenced by
      increased poly(ADP-ribose) polymerase cleavage and reduction in procaspase3. From
      these results, we conclude that ERRP is a potent inhibitor of growth of BxPC-3
      pancreatic cancer cells, which could be due to attenuation of EGFR cellular
      signaling processes. We also suggest that ERRP could be a potential therapeutic
      agent for pancreatic cancer.

PMID- 15867389
TI  - Poly(ADP-ribose) polymerase-1 could facilitate the religation of topoisomerase I
      linked DNA inhibited by camptothecin.
AB  - Poly(ADP-ribose) polymerase-1 (PARP-1) is known to have an important role in
      camptothecin sensitivity and interacts with topoisomerase I. In the present
      study, the impact of PARP-1 on the topoisomerase I-DNA complex stabilized by
      camptothecin was assessed. It was shown that NH2 terminus-truncated topoisomerase
      I (amino acids 201-765) showed at least 4-fold less sensitivity to camptothecin
      than full-length topoisomerase I in the oligonucleotide religation assay. PARP-1
      could prevent the action of camptothecin on the religation activity of full
      length topoisomerase I, which is linked to DNA in a stoichiometrical manner.
      However, the religation activity of NH2 terminus-truncated topoisomerase I, which
      is linked to DNA, could not be enhanced by PARP-1 in the presence of
      camptothecin. Both full-length and NH2 terminus-truncated topoisomerase I
      interact with PARP-1. This data suggests that PARP-1 destabilizes the
      topoisomerase I-camptothecin-DNA complex with the participation of the NH2
      terminal domain of topoisomerase I. Poly(ADP-ribosyl)ation of topoisomerase I by
      PARP-1 in the presence its substrate, NAD, could also promote the religation
      activity of full-length topoisomerase I as well as NH2 terminus-truncated
      topoisomerase I. PARP-1 inhibitors (3-aminobenzamide, PJ34) could inhibit this
      process. Therefore, PARP-1 could facilitate the religation activity of
      topoisomerase I by itself through topoisomerase I-PARP-1 interaction (PARP-1
      action) or by the formation of poly(ADP-ribosyl)ation of topoisomerase I (PARP
      1/NAD action). This study also implies that PARP-1 and PARP-1/NAD actions need to
      be highly regulated by cellular factors for camptothecin to exert its
      cytotoxicity inside the cells. We propose ATP to be one of the important
      regulatory factors.

PMID- 15867388
TI  - The synergistic combination of the farnesyl transferase inhibitor lonafarnib and
      paclitaxel enhances tubulin acetylation and requires a functional tubulin
      deacetylase.
AB  - Farnesyl transferase (FT) inhibitors (FTI) are anticancer agents developed to
      target oncogenic Ras proteins by inhibiting Ras farnesylation. FTIs potently
      synergize with paclitaxel and other microtubule-stabilizing drugs; however, the
      mechanistic basis underlying this synergistic interaction remains elusive. Here
      we show that the FTI lonafarnib affects the microtubule cytoskeleton resulting in
      microtubule bundle formation, increased microtubule stabilization and
      acetylation, and suppression of microtubule dynamics. Notably, treatment with the
      combination of low doses of lonafarnib with paclitaxel markedly enhanced tubulin
      acetylation (a marker of microtubule stability) as compared with either drug
      alone. This synergistic effect correlated with FT inhibition and was accompanied
      by a synergistic increase in mitotic arrest and cell death. Mechanistically, we
      show that the combination of lonafarnib and paclitaxel inhibits the in vitro
      deacetylating activity of the only known tubulin deacetylase, histone deacetylase
      6 (HDAC6). In addition, the lonafarnib/taxane combination is synergistic only in
      cells lines expressing the wild-type HDAC6, but not a catalytic-mutant HDAC6,
      revealing that functional HDAC6 is required for the synergy of lonafarnib with
      taxanes. Furthermore, tubacin, a specific HDAC6 inhibitor, synergistically
      enhanced tubulin acetylation in combination with paclitaxel, similar to the
      combination of lonafarnib and paclitaxel. Taken together, these data suggest a
      relationship between FT inhibition, HDAC6 function, and cell death, providing
      insight into the putative molecular basis of the lonafarnib/taxane synergistic
      antiproliferative combination.

PMID- 15867390
TI  - The role of growth factor receptor pathways in human breast cancer cells adapted
      to long-term estrogen deprivation.
AB  - To study the long-term effects of estrogen deprivation on breast cancer, MCF-7Ca
      human estrogen receptor-positive breast cancer cells stably transfected with
      human aromatase gene were cultured in the steroid-depleted medium for 6 to 8
      months until they had acquired the ability to grow. Proliferation of these cells
      (UMB-1Ca) was accompanied by increased expression of human epidermal growth
      factor receptor 2, increased activation of AKT through phosphorylation at Ser473
      and Thr308, and increased invasion compared with parental MCF-7Ca cells. Estrogen
      receptor expression was also increased 5-fold. Although growth was inhibited by
      the antiestrogen fulvestrant, the IC50 was 100-fold higher than for parental MCF
      7Ca cells. Aromatase inhibitor letrozole also inhibited growth at 10,000-fold
      higher concentration than required for MCF-7Ca cells, whereas anastrozole,
      exemestane, formestane, and tamoxifen were ineffective at 100 nmol/L. Growth of
      UMB-1Ca cells was inhibited by phosphatidylinositol 3-kinase inhibitor wortmannin
      (IC50 approximately 25 nmol/L) and epidermal growth factor receptor kinase
      inhibitor gefitinib (ZD 1839; IC50 approximately 10 micromol/L) whereas parental
      MCF-7Ca cells were insensitive to these agents. Concomitant treatment of UMB-1Ca
      cells with the signal transduction inhibitors and anastrozole and tamoxifen
      restored their growth inhibitory effects. These studies show that estrogen
      deprivation results in up-regulation of growth factor signaling pathways, which
      leads to a more aggressive and hormone refractory phenotype. Cross-talk between
      ER and growth factor signaling was evident as inhibition of these pathways could
      restore estrogen responsiveness to these cells.

PMID- 15867391
TI  - Elucidation of thioredoxin as a molecular target for antitumor quinols.
AB  - Heteroaromatic quinols 4-(benzothiazol-2-yl)-4-hydroxycyclohexa-2,5-dienone (1)
      and 4-(1-benzenesulfonyl-1H-indol-2-yl)-4-hydroxycyclohexa-2,5-dienone (2)
      exhibit potent and selective antitumor activity against colon, renal, and breast
      carcinoma cell lines in vitro (GI50 < 500 nmol/L). In vivo growth inhibition of
      renal, colon, and breast xenografts has been observed. Profound G2-M cell cycle
      block accompanied down-regulation of cdk1 gene transcription was corroborated by
      decreased CDK1 protein expression following treatment of HCT 116 cells with
      growth inhibitory concentrations of 1 or 2. The chemical structure of the quinol
      pharmacophore 4-(hydroxycyclohexa-2,5-dienone) suggested that these novel agents
      would readily react with nucleophiles in a double Michael (beta-carbon) addition.
      Indeed, COMPARE analysis within the National Cancer Institute database revealed a
      number of chemically related quinone derivatives that could potentially react
      with sulfur nucleophiles in a similar manner and suggested that
      thioredoxin/thioredoxin reductase signal transduction could be a putative target.
      Molecular modeling predicted covalent irreversible binding between quinol
      analogues and cysteine residues 32 and 35 of thioredoxin, thereby inhibiting
      enzyme activity. Binding has been confirmed, via mass spectrometry, between
      reduced human thioredoxin and 1. Microarray analyses of untreated HCT 116 cells
      and those exposed to either 1 (1 micromol/L) or 2 (500 nmol/L and 1 micromol/L)
      determined that of > or =10,000 cancer-related genes, expression of thioredoxin
      reductase was up-regulated >3-fold. Furthermore, quinols 1 and 2 inhibited
      insulin reduction, catalyzed by thioredoxin/thioredoxin reductase signaling in a
      dose-dependent manner (IC50 < 6 micromol/L). Results are consistent with a
      mechanism of action of novel antitumor quinols involving inhibition of the small
      redox protein thioredoxin.

PMID- 15867392
TI  - Cancer immunotherapy based on killing of Salmonella-infected tumor cells.
AB  - A major obstacle for the development of effective immunotherapy is the ability of
      tumors to escape the immune system. The possibility to kill tumor cells because
      they are recognized as infected rather than as malignant could help overcome
      immune escape mechanisms. Here we report a conceptually new approach of cancer
      immunotherapy based on in vivo infection of tumors and killing of infected tumor
      cells. Attenuated but still invasive, Salmonella typhimurium can be successfully
      exploited to invade melanoma cells that can present antigenic determinants of
      bacterial origin and become targets for anti-Salmonella-specific T cells.
      However, to fully appreciate the anticancer therapeutic properties of S.
      typhimurium, tumor-bearing mice need to be vaccinated against S. typhimurium
      before intratumoral Salmonella injection. Tumor infection when coupled to anti
      Salmonella vaccination leads to 50% to 100% tumor-free mice with a better outcome
      on larger tumors. Invasive Salmonella also exert an indirect toxic effect on
      tumor cells through the recruitment of inflammatory cells and the cross
      presentation of tumor antigens, which allow induction of tumor-specific immune
      response. This is effective in retarding the growth of untreated established
      distant tumors and in protecting the mice from subsequent tumor challenges.

PMID- 15867393
TI  - Tumor necrosis factor reduces brain tumor growth by enhancing macrophage
      recruitment and microcyst formation.
AB  - Recent findings implicate macrophages and some of their secreted products,
      especially tumor necrosis factor (TNF), as tumor promoters. Inhibitors of these
      inflammatory components are currently regarded as potential therapeutic tools to
      block tumor progression. Here, we show that infiltrating macrophages represented
      a significant population of nonneoplastic cells within malignant gliomas, in
      which they were the exclusive producers of TNF. Contrary to the reported pro
      oncogenic effects of TNF in other types of solid tumors, glioma-bearing mice
      deficient in TNF developed larger tumors and had reduced survival compared with
      their wild-type controls. Histologic examinations revealed that glioma volume was
      negatively correlated with the number of macrophages and small cavities called
      microcysts. Overall, our results support the concept that macrophages alter brain
      tumor development through a TNF-dependent process that culminates in the
      formation of microcysts. This raises the question of whether anti-inflammatory
      drugs, such as those commonly administrated to patients with brain cancer, could
      interfere with antitumor mechanisms.

PMID- 15867394
TI  - Intratumoral T-cell infiltrates and MHC class I expression in patients with stage
      IV melanoma.
AB  - The infiltration of tumors by T cells has been shown to correlate with prolonged
      patients' survival. However, it remains unclear why only some tumors are
      infiltrated with T cells. This study was designed to investigate possible
      correlations between intratumoral T-cell infiltrates and the expression of cancer
      associated antigens and MHC class I and II molecules in patients with melanoma.
      Fresh frozen samples from 124 stage IV melanoma patients were analyzed by
      immunohistochemistry for the expression of Melan-A/MART-1, tyrosinase, gp100, NY
      ESO-1, and MHC class I and II. Intratumoral T-cell and B-cell infiltrates were
      detected by staining with anti-CD4, anti-CD8, anti-CD3, and L26 antibodies. The
      NY-ESO-1 serum antibody status was assessed by Western blot analysis.
      Intratumoral CD8+ and CD4+ T cells were detected in 63.9% and 71.3% of patients,
      respectively. We observed a significant heterogeneity of the expression of the
      melanocyte differentiation antigens, NY-ESO-1, and MHC class I and II molecules.
      The only significant correlation was found between the expression of MHC class I
      and the presence of CD4+ and CD8+ T cells (P < 0.0001). There was a strong
      association between these two variables with respect to the density and
      distribution of infiltrating T cells and the pattern of MHC class I expression
      (focal versus homogenous). Intratumoral T-cell infiltration is closely correlated
      with the MHC class I expression but not with the expression of differentiation
      antigens, cancer-associated antigens, or MHC class II molecules. These results
      may have implications for the definition of prognostic variables and for the
      identification of patients who may benefit from antigen-specific cancer
      immunotherapy.

PMID- 15867395
TI  - Natural killer and NK-Like T-cell activation in colorectal carcinoma patients
      treated with autologous tumor-derived heat shock protein 96.
AB  - Heat shock proteins (HSPs) are involved in the activation of both adaptive and
      innate immune systems. Here, we report that vaccination with autologous tumor
      derived HSP96 of colorectal cancer patients, radically resected for liver
      metastases, induced a significant boost of natural killer (NK) activity detected
      as cytokine secretion and cytotoxicity in the presence of NK-sensitive targets.
      Increased NK activity was associated with a raise in CD3-CD56+ NK and/or
      CD3+CD56+ NK-like T cells, displaying enhanced expression of NKG2D and/or NKp46
      receptors. Up-regulated expression of CD83 and CD40 and increased interleukin-12
      release on stimulation were observed in CD14+ cells from post-HSP96 peripheral
      blood mononuclear cells, suggesting an indirect pathway of NK stimulation by
      HSP96-activated monocytes. Additionally, CD3-CD56+ and CD3+CD56+ lymphocytes were
      found to undergo functional and phenotypic activation on in vitro exposure to
      HSP96 even in the absence of monocytes, supporting a potential direct activity of
      HSP96 on these cell subsets. This evidence was confirmed by the specific binding
      of FITC-conjugated HSP96 to a subset of both CD3-CD56+ and CD3+CD56+ cells in
      peripheral blood mononuclear cells from colorectal cancer patients. Altogether,
      these findings identify the activation of the NK compartment as an additional
      immunologic effect of autologous tumor-derived HSP96 administration in cancer
      patients.

PMID- 15867396
TI  - Peroxisome proliferator-activated receptor delta and gamma agonists
      differentially alter tumor differentiation and progression during mammary
      carcinogenesis.
AB  - Peroxisome proliferator-activated receptor (PPAR) represents a ligand-dependent
      nuclear receptor family that regulates multiple metabolic processes associated
      with fatty acid beta-oxidation, glucose utilization, and cholesterol transport.
      These and other receptor-mediated actions pertain to their role in hypolipidemic
      and antidiabetic therapies and as potential targets for cancer chemopreventive
      agents. The present study evaluated the chemopreventive activity of two highly
      potent and selective PPARgamma and PPARdelta agonists in a progestin- and
      carcinogen-induced mouse mammary tumorigenesis model. Animals treated with the
      PPARgamma agonist GW7845 exhibited a moderate delay in tumor formation. In
      contrast, animals treated with the PPARdelta agonist GW501516 showed accelerated
      tumor formation. Significantly, tumors from GW7845-treated mice were
      predominantly ductal adenocarcinomas, whereas tumors from GW501516-treated
      animals were adenosquamous and squamous cell carcinomas. Gene expression analysis
      of tumors arising from GW7845- and GW501516-treated mice identified expression
      profiles that were distinct from each other and from untreated control tumors of
      the same histopathology. Only tumors from mice treated with the PPARgamma agonist
      expressed estrogen receptor-alpha in luminal transit cells, suggesting increased
      ductal progenitor cell expansion. Tumors from mice treated with the PPARdelta
      agonist exhibited increased PPARdelta levels and activated 3-phosphoinositide
      dependent protein kinase-1 (PDK1), which co-associated, suggesting a link between
      the known oncogenic activity of PDK1 in mammary epithelium and PPARdelta
      activation. These results indicate that PPARdelta and PPARgamma agonists produce
      diverse, yet profound effects on mammary tumorigenesis that give rise to
      distinctive histopathologic patterns of tumor differentiation and tumor
      development.

PMID- 15867398
TI  - Summaries for patients. Improving cholesterol levels: is a low-fat diet high in
      plant-based foods better than a typical low-fat diet?

PMID- 15867397
TI  - Chemoprevention of UV light-induced skin tumorigenesis by inhibition of the
      epidermal growth factor receptor.
AB  - The epidermal growth factor receptor (EGFR) is activated in skin cells following
      UV irradiation, the primary cause of nonmelanoma skin cancer. The EGFR inhibitor
      AG1478 prevented the UV-induced activation of EGFR and of downstream signaling
      pathways through c-Jun NH2-terminal kinases, extracellular signal-regulated
      kinases, p38 kinase, and phosphatidylinositol 3-kinase in the skin. The extent to
      which the UV-induced activation of EGFR influences skin tumorigenesis was
      determined in genetically initiated v-ras(Ha) transgenic Tg.AC mice, which have
      enhanced susceptibility to skin carcinogenesis. Topical treatment or i.p.
      injection of AG1478 before UV exposure blocked the UV-induced activation of EGFR
      in the skin and decreased skin tumorigenesis in Tg.AC mice. AG1478 treatment
      before each of several UV exposures decreased the number of papillomas arising
      and the growth of these tumors by approximately 50% and 80%, respectively.
      Inhibition of EGFR suppressed proliferation, increased apoptotic cell death, and
      delayed the onset of epidermal hyperplasia following UV irradiation. Genetic
      ablation of Egfr similarly delayed epidermal hyperplasia in response to UV
      exposure. Thus, the UV-induced activation of EGFR promotes skin tumorigenesis by
      suppressing cell death, augmenting cell proliferation, and accelerating epidermal
      hyperplasia in response to UV. These results suggest that EGFR may be an
      appropriate target for the chemoprevention of UV-induced skin cancer.

PMID- 15867399
TI  - Summaries for patients. Cost-effectiveness of alendronate in postmenopausal women
      with low bone mass without osteoporosis or previous fracture.

PMID- 15867400
TI  - Summaries for patients. Can special cholesterol tests help predict a person's
      risk for atherosclerosis?

PMID- 15867401
TI  - Summaries for patients. Bloodstream infection in patients with Lyme disease.

PMID- 15867402
TI  - Summaries for patients. Exercise for low back pain.

PMID- 15867403
TI  - Summaries for patients. Best types of exercise for low back pain.

PMID- 15867404
TI  - The effect of a plant-based diet on plasma lipids in hypercholesterolemic adults:
      a randomized trial.
AB  - BACKGROUND: A variety of food combinations can be used to meet national U.S.
      guidelines for obtaining 30% of energy or less from total fat and 10% of energy
      or less from saturated fat. OBJECTIVE: To contrast plasma lipid responses to 2
      low-fat diet patterns. DESIGN: Randomized clinical trial. SETTING: 4-week
      outpatient feeding study with weight held constant. PARTICIPANTS: 120 adults 30
      to 65 years of age with prestudy low-density lipoprotein (LDL) cholesterol
      concentrations of 3.3 to 4.8 mmol/L (130 to 190 mg/dL), body mass index less than
      31 kg/m2, estimated dietary saturated fat at least 10% of calories, and otherwise
      general good health. MEASUREMENTS: Plasma lipid levels. INTERVENTION: Two diets,
      the Low-Fat diet and the Low-Fat Plus diet, designed to be identical in total
      fat, saturated fat, protein, carbohydrate, and cholesterol content, consistent
      with former American Heart Association Step I guidelines. The Low-Fat diet was
      relatively typical of a low-fat U.S. diet. The Low-Fat Plus diet incorporated
      considerably more vegetables, legumes, and whole grains, consistent with the 2000
      American Heart Association revised guidelines. RESULTS: Four-week changes in the
      Low-Fat and Low-Fat Plus groups were -0.24 mmol/L (-9.2 mg/dL) versus -0.46
      mmol/L (-17.6 mg/dL) for total cholesterol (P = 0.01) and -0.18 mmol/L (-7.0
      mg/dL) versus -0.36 mmol/L (-13.8 mg/dL) for LDL cholesterol (P = 0.02); between
      group differences were -0.22 mmol/L (-9 mg/dL) (95% CI, -0.05 to -0.39 mmol/L [-2
      to -15 mg/dL]) and -0.18 mmol/L (-7 mg/dL) (CI, -0.04 to -0.32 mmol/L [-2 to -12
      mg/dL]) for total and LDL cholesterol, respectively. The 2 diet groups did not
      differ significantly in high-density lipoprotein cholesterol and triglyceride
      levels. LIMITATIONS: 4-week duration. CONCLUSIONS: Previous national dietary
      guidelines primarily emphasized avoiding saturated fat and cholesterol; as a
      result, the guidelines probably underestimated the potential LDL cholesterol
      lowering effect of diet. In this study, emphasis on including nutrient-dense
      plant-based foods, consistent with recently revised national guidelines,
      increased the total and LDL cholesterol-lowering effect of a low-fat diet.

PMID- 15867405
TI  - Cost-effectiveness of alendronate therapy for osteopenic postmenopausal women.
AB  - BACKGROUND: Treatment guidelines recommend drug treatment to prevent fractures
      for some postmenopausal women who have low bone mass (osteopenia) but do not have
      osteoporosis or a history of clinical fractures. OBJECTIVE: To estimate the
      societal costs and health benefits of alendronate drug treatment to prevent
      fractures in postmenopausal women with osteopenia. DESIGN: Markov model with 8
      health states: no fracture, post-distal forearm fracture, post-clinical vertebral
      fracture, post-radiographic (but clinically inapparent) vertebral fracture, post
      hip fracture, post-hip and vertebral fractures, post-other fracture, and death.
      DATA SOURCES: Population-based studies of age-specific fracture rates and costs,
      prospectively measured estimates of disutility after fractures, and the Fracture
      Intervention Trial of alendronate versus placebo to prevent fracture. TARGET
      POPULATION: Postmenopausal women 55 to 75 years of age with femoral neck T-scores
      between -1.5 and -2.4. TIME HORIZON: Lifetime. PERSPECTIVE: Societal.
      INTERVENTIONS: Five years of alendronate therapy or no drug treatment. OUTCOME
      MEASURES: Costs, quality-adjusted life-years, and incremental cost-effectiveness
      ratios. RESULTS OF BASE-CASE ANALYSIS: For women with no additional fracture risk
      factors, the cost per quality-adjusted life-year gained ranged from 70,000
      dollars to 332,000 dollars, depending on age and femoral neck bone density.
      RESULTS OF SENSITIVITY ANALYSES: Results were sensitive to changes in fracture
      risk reduction attributable to alendronate and alendronate cost. LIMITATIONS:
      Results apply only to postmenopausal white women residing in the United States.
      CONCLUSION: Alendronate therapy for postmenopausal women with femoral neck T
      scores better than -2.5 and no history of clinical fractures or other bone
      mineral density-independent risk factors for fracture is not cost-effective,
      assuming U.S. costs of alendronate and currently available estimates of
      alendronate efficacy in osteopenic women.

PMID- 15867406
TI  - Advanced lipoprotein testing does not improve identification of subclinical
      atherosclerosis in young adults: the Bogalusa Heart Study.
AB  - BACKGROUND: The clinical value of advanced lipoprotein testing relative to
      traditional lipid testing remains controversial. To date, no studies have
      evaluated associations between advanced lipoprotein testing and subclinical
      atherosclerosis in healthy young adults. OBJECTIVE: To determine whether advanced
      lipoprotein testing using vertical-spin density-gradient ultracentrifugation
      better predicts carotid intima-media thickness, a validated measure of
      subclinical atherosclerosis, than does traditional lipoprotein testing in
      asymptomatic young adults. DESIGN: Cross-sectional community-based study.
      SETTING: Bogalusa, Louisiana. PARTICIPANTS: 311 randomly selected adults from the
      Bogalusa Heart Study who were 20 to 38 years of age. MEASUREMENTS: The authors
      performed advanced lipoprotein testing using vertical-spin density-gradient
      ultracentrifugation, traditional testing using enzymatic methods, and Friedewald
      formula estimation of low-density lipoprotein cholesterol levels. A certified
      reader blinded to lipoprotein results determined carotid intima-media thickness
      by B-mode ultrasonography. C-statistics from area under the receiver-operating
      characteristic curves (AUCs) derived from multivariable regression models were
      compared. RESULTS: Lipid values obtained with advanced lipoprotein testing did
      not predict carotid intima-media thickness better than traditionally measured
      lipid values in 236 participants for whom all data were available. A model using
      traditional lipoprotein measures (AUC, 0.754 [95% CI, 0.690 to 0.812]) did not
      differ significantly from a model using advanced lipoprotein measures (AUC, 0.779
      [CI, 0.662 to 0.871]) for prediction of carotid intima-media thickness (P > 0.2).
      Subclass pattern of LDL, lipoprotein(a) cholesterol, intermediate-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol subclasses, and
      very-low-density lipoprotein subclasses did not improve the performance of models
      for prediction of carotid intima-media thickness. LIMITATIONS: The study was
      cross-sectional, cardiac events were not determined, and only 1 method of
      advanced lipoprotein testing was used. CONCLUSIONS: Advanced lipoprotein testing
      using vertical-spin density-gradient ultracentrifugation did not improve
      prediction of carotid intima-media thickness in young adults and may not be
      useful for assessing cardiovascular risk in this population.

PMID- 15867407
TI  - Brief communication: hematogenous dissemination in early Lyme disease.
AB  - BACKGROUND: Bloodstream invasion in Lyme disease has been difficult to study
      because until recently blood culture methods were too insensitive to detect
      spirochetemia. OBJECTIVE: To evaluate the clinical and laboratory features of
      spirochetemic patients. DESIGN: Cross-sectional study. SETTING: Lyme Disease
      Diagnostic Center in Valhalla, New York, 1997 to 2002. PATIENTS: 213 untreated
      adults with erythema migrans. INTERVENTION: Blood culture for Borrelia
      burgdorferi. MEASUREMENTS: Symptom scores and selected laboratory measures.
      RESULTS: Spirochetemia was found in 93 (43.7%) patients. Spirochetemic patients
      were more often symptomatic (89.2% vs. 74.2%; P = 0.006) and more often had
      multiple erythema migrans lesions (41.9% vs. 15.0%; P < 0.001) than patients
      without spirochetemia. However, 8 (22.9%) of the 35 asymptomatic patients with a
      single skin lesion nevertheless had a positive blood culture. Risk for
      spirochetemia was present the day the patient noticed the lesion and continued
      for more than 2 weeks. LIMITATIONS: Long-term outcome data were not available.
      CONCLUSIONS: The high rate, early onset, and prolonged duration of risk for
      spirochetemia explain why untreated patients with erythema migrans are at risk
      for dissemination of B. burgdorferi to anatomic sites beyond the lesion site.
      Differences in the strain of the infecting spirochete, as well as host factors,
      may be important determinants of hematogenous dissemination.

PMID- 15867408
TI  - Five system barriers to achieving ultrasafe health care.
AB  - Although debate continues over estimates of the amount of preventable medical
      harm that occurs in health care, there seems to be a consensus that health care
      is not as safe and reliable as it might be. It is often assumed that copying and
      adapting the success stories of nonmedical industries, such as civil aviation and
      nuclear power, will make medicine as safe as these industries. However, the
      solution is not that simple. This article explains why a benchmarking approach to
      safety in high-risk industries is needed to help translate lessons so that they
      are usable and long lasting in health care. The most important difference among
      industries lies not so much in the pertinent safety toolkit, which is similar for
      most industries, but in an industry's willingness to abandon historical and
      cultural precedents and beliefs that are linked to performance and autonomy, in a
      constant drive toward a culture of safety. Five successive systemic barriers
      currently prevent health care from becoming an ultrasafe industrial system: the
      need to limit the discretion of workers, the need to reduce worker autonomy, the
      need to make the transition from a craftsmanship mindset to that of equivalent
      actors, the need for system-level (senior leadership) arbitration to optimize
      safety strategies, and the need for simplification. Finally, health care must
      overcome 3 unique problems: a wide range of risk among medical specialties,
      difficulty in defining medical error, and various structural constraints (such as
      public demand, teaching role, and chronic shortage of staff). Without such a
      framework to guide development, ongoing efforts to improve safety by adopting the
      safety strategies of other industries may yield reduced dividends. Rapid progress
      is possible only if the health care industry is willing to address these
      structural constraints needed to overcome the 5 barriers to ultrasafe
      performance.

PMID- 15867409
TI  - Meta-analysis: exercise therapy for nonspecific low back pain.
AB  - BACKGROUND: Exercise therapy is widely used as an intervention in low back pain.
      OBJECTIVE: To evaluate the effectiveness of exercise therapy in adult nonspecific
      acute, subacute, and chronic low back pain versus no treatment and other
      conservative treatments. DATA SOURCES: MEDLINE, EMBASE, PsychInfo, CINAHL, and
      Cochrane Library databases to October 2004; citation searches and bibliographic
      reviews of previous systematic reviews. STUDY SELECTION: Randomized, controlled
      trials evaluating exercise therapy for adult nonspecific low back pain and
      measuring pain, function, return to work or absenteeism, and global improvement
      outcomes. DATA EXTRACTION: Two reviewers independently selected studies and
      extracted data on study characteristics, quality, and outcomes at short-,
      intermediate-, and long-term follow-up. DATA SYNTHESIS: 61 randomized, controlled
      trials (6390 participants) met inclusion criteria: acute (11 trials), subacute (6
      trials), and chronic (43 trials) low back pain (1 trial was unclear). Evidence
      suggests that exercise therapy is effective in chronic back pain relative to
      comparisons at all follow-up periods. Pooled mean improvement (of 100 points) was
      7.3 points (95% CI, 3.7 to 10.9 points) for pain and 2.5 points (CI, 1.0 to 3.9
      points) for function at earliest follow-up. In studies investigating patients
      (people seeking care for back pain), mean improvement was 13.3 points (CI, 5.5 to
      21.1 points) for pain and 6.9 points (CI, 2.2 to 11.7 points) for function,
      compared with studies where some participants had been recruited from a general
      population (for example, with advertisements). Some evidence suggests
      effectiveness of a graded-activity exercise program in subacute low back pain in
      occupational settings, although the evidence for other types of exercise therapy
      in other populations is inconsistent. In acute low back pain, exercise therapy
      and other programs were equally effective (pain, 0.03 point [CI, -1.3 to 1.4
      points]). LIMITATIONS: Limitations of the literature, including low-quality
      studies with heterogeneous outcome measures inconsistent and poor reporting, and
      possibility of publication bias. CONCLUSIONS: Exercise therapy seems to be
      slightly effective at decreasing pain and improving function in adults with
      chronic low back pain, particularly in health care populations. In subacute low
      back pain populations, some evidence suggests that a graded-activity program
      improves absenteeism outcomes, although evidence for other types of exercise is
      unclear. In acute low back pain populations, exercise therapy is as effective as
      either no treatment or other conservative treatments.

PMID- 15867410
TI  - Systematic review: strategies for using exercise therapy to improve outcomes in
      chronic low back pain.
AB  - BACKGROUND: Exercise therapy encompasses a heterogeneous group of interventions.
      There continues to be uncertainty about the most effective exercise approach in
      chronic low back pain. PURPOSE: To identify particular exercise intervention
      characteristics that decrease pain and improve function in adults with
      nonspecific chronic low back pain. DATA SOURCES: MEDLINE, EMBASE, PsychInfo,
      CINAHL, and Cochrane Library databases to October 2004 and citation searches and
      bibliographic reviews of previous systematic reviews. STUDY SELECTION:
      Randomized, controlled trials evaluating exercise therapy in populations with
      chronic (>12 weeks duration) low back pain. DATA EXTRACTION: Two reviewers
      independently extracted data on exercise intervention characteristics: program
      design (individually designed or standard program), delivery type (independent
      home exercises, group, or individual supervision), dose or intensity (hours of
      intervention time), and inclusion of additional conservative interventions. DATA
      SYNTHESIS: 43 trials of 72 exercise treatment and 31 comparison groups were
      included. Bayesian multivariable random-effects meta-regression found improved
      pain scores for individually designed programs (5.4 points [95% credible interval
      (CrI), 1.3 to 9.5 points]), supervised home exercise (6.1 points [CrI, -0.2 to
      12.4 points]), group (4.8 points [CrI, 0.2 to 9.4 points]), and individually
      supervised programs (5.9 points [CrI, 2.1 to 9.8 points]) compared with home
      exercises only. High-dose exercise programs fared better than low-dose exercise
      programs (1.8 points [CrI, -2.1 to 5.5 points]). Interventions that included
      additional conservative care were better (5.1 points [CrI, 1.8 to 8.4 points]). A
      model including these most effective intervention characteristics would be
      expected to demonstrate important improvement in pain (18.1 points [CrI, 11.1 to
      25.0 points] compared with no treatment and 13.0 points [CrI, 6.0 to 19.9 points]
      compared with other conservative treatment) and small improvement in function
      (5.5 points [CrI, 0.5 to 10.5 points] compared with no treatment and 2.7 points
      [CrI, -1.7 to 7.1 points] compared with other conservative treatment). Stretching
      and strengthening demonstrated the largest improvement over comparisons.
      LIMITATIONS: Limitations of the literature, including low-quality studies with
      heterogeneous outcome measures and inconsistent and poor reporting; publication
      bias. CONCLUSIONS: Exercise therapy that consists of individually designed
      programs, including stretching or strengthening, and is delivered with
      supervision may improve pain and function in chronic nonspecific low back pain.
      Strategies should be used to encourage adherence. Future studies should test this
      multivariable model and further assess specific patient-level characteristics and
      exercise types.

PMID- 15867411
TI  - Narrative review: alternative causes for elevated cardiac troponin levels when
      acute coronary syndromes are excluded.
AB  - Current guidelines for the diagnosis of non-ST-segment elevation myocardial
      infarction are largely based on an elevated troponin level. While this rapid and
      sensitive blood test is certainly valuable in the appropriate setting, its
      widespread use in a variety of clinical scenarios may lead to the detection of
      troponin elevation in the absence of thrombotic acute coronary syndromes. Many
      diseases, such as sepsis, hypovolemia, atrial fibrillation, congestive heart
      failure, pulmonary embolism, myocarditis, myocardial contusion, and renal
      failure, can be associated with an increase in troponin level. These elevations
      may arise from various causes other than thrombotic coronary artery occlusion.
      Given the lack of any supportive data at present, patients with nonthrombotic
      troponin elevation should not be treated with antithrombotic and antiplatelet
      agents. Rather, the underlying cause of the troponin elevation should be
      targeted. However, troponin elevation in the absence of thrombotic acute coronary
      syndromes still retains prognostic value. Thus, cardiac troponin elevations are
      common in numerous disease states and do not necessarily indicate the presence of
      a thrombotic acute coronary syndrome. While troponin is a sensitive biomarker to
      "rule out" non-ST-segment elevation myocardial infarction, it is less useful to
      "rule in" this event because it may lack specificity for acute coronary
      syndromes.

PMID- 15867412
TI  - Diet and cholesterol reduction.

PMID- 15867413
TI  - Osteopenia: to treat or not to treat?

PMID- 15867414
TI  - Computed tomography and ultrasonography to detect appendicitis.

PMID- 15867415
TI  - Computed tomography and ultrasonography to detect appendicitis.

PMID- 15867416
TI  - Computed tomography and ultrasonography to detect appendicitis.

PMID- 15867417
TI  - Defining the role of computed tomographic pulmonary angiography in suspected
      pulmonary embolism.

PMID- 15867418
TI  - Defining the role of computed tomographic pulmonary angiography in suspected
      pulmonary embolism.

PMID- 15867419
TI  - Defining the role of computed tomographic pulmonary angiography in suspected
      pulmonary embolism.

PMID- 15867420
TI  - Resolution of severe digital ulceration during a course of Bosentan therapy.

PMID- 15867421
TI  - Chromosome 7 deletions are associated with unfavorable prognosis in myelofibrosis
      with myeloid metaplasia.

PMID- 15867422
TI  - Hematopoietic cell transplantation from unrelated donors as an effective therapy
      for older patients (> or = 60 years) with active myeloid malignancies.

PMID- 15867423
TI  - No cardiac toxicity associated with alemtuzumab therapy for mycosis
      fungoides/Sezary syndrome.

PMID- 15867424
TI  - Growth requirements and immunophenotype of acute lymphoblastic leukemia
      progenitors.

PMID- 15867425
TI  - Clonal expansion of a new MLL rearrangement in the absence of leukemia.

PMID- 15867426
TI  - Generation and evolutionary fate of insertions of organelle DNA in the nuclear
      genomes of flowering plants.
AB  - Nuclear genomes are exposed to a continuous influx of DNA from mitochondria and
      plastids. We have characterized the structure of approximately 750 kb of
      organelle DNA, distributed among 13 loci, in the nuclear genomes of Arabidopsis
      and rice. These segments are large and migrated to the nucleus quite recently,
      allowing us to reconstruct their evolution. Two general types of nuclear
      insertions coexist; one is characterized by long sequence stretches that are
      colinear with organelle DNA, the other type consists of mosaics of organelle DNA,
      often derived from both plastids and mitochondria. The levels of sequence
      divergence of the two types exclude their common descent, implying that at least
      two independent modes of DNA transfer from organelle to nucleus operate. The post
      integration fate of organelle DNA is characterized by a predominance of
      transition mutations, associated with the gradual amelioration of the integrated
      sequence to the nucleotide composition of the host chromosome. Deletion of
      organelle DNA at these loci is essentially balanced by insertions of nonorganelle
      DNA. Deletions are associated with the removal of DNA between perfect repeats,
      indicating that they originate by replication slippage.

PMID- 15867427
TI  - Under the genomic radar: the stealth model of Alu amplification.
AB  - Alu elements are the most successful SINEs (Short INterspersed Elements) in
      primate genomes and have reached more than 1,000,000 copies in the human genome.
      The amplification of most Alu elements is thought to occur through a limited
      number of hyperactive "master" genes that produce a high number of copies during
      long evolutionary periods of time. However, the existence of long-lived, low
      activity Alu lineages in the human genome suggests a more complex propagation
      mechanism. Using both computational and wet-bench approaches, we reconstructed
      the evolutionary history of the AluYb lineage, one of the most active Alu
      lineages in the human genome. We show that the major AluYb lineage expansion in
      humans is a species-specific event, as nonhuman primates possess only a handful
      of AluYb elements. However, the oldest existing AluYb element resided in an
      orthologous position in all hominoid primate genomes examined, demonstrating that
      the AluYb lineage originated 18-25 million years ago. Thus, the history of the
      AluYb lineage is characterized by approximately 20 million years of
      retrotranspositional quiescence preceding a major expansion in the human genome
      within the past few million years. We suggest that the evolutionary success of
      the Alu family may be driven at least in part by "stealth-driver" elements that
      maintain low retrotranspositional activity over extended periods of time and
      occasionally produce short-lived hyperactive copies responsible for the formation
      and remarkable expansion of Alu elements within the genome.

PMID- 15867428
TI  - Evolution of base-substitution gradients in primate mitochondrial genomes.
AB  - Inferences of phylogenies and dates of divergence rely on accurate modeling of
      evolutionary processes; they may be confounded by variation in substitution rates
      among sites and changes in evolutionary processes over time. In vertebrate
      mitochondrial genomes, substitution rates are affected by a gradient along the
      genome of the time spent being single-stranded during replication, and different
      types of substitutions respond differently to this gradient. The gradient is
      controlled by biological factors including the rate of replication and
      functionality of repair mechanisms; little is known, however, about the
      consistency of the gradient over evolutionary time, or about how evolution of
      this gradient might affect phylogenetic analysis. Here, we evaluate the evolution
      of response to this gradient in complete primate mitochondrial genomes, focusing
      particularly on A-->G substitutions, which increase linearly with the gradient.
      We developed a methodology to evaluate the posterior probability densities of the
      response parameter space, and used likelihood ratio tests and mixture models with
      different numbers of classes to determine whether groups of genomes have evolved
      in a similar fashion. Substitution gradients usually evolve slowly in primates,
      but there have been at least two large evolutionary jumps: on the lineage leading
      to the great apes, and a convergent change on the lineage leading to baboons
      (Papio). There have also been possible convergences at deeper taxonomic levels,
      and different types of substitutions appear to evolve independently. The
      placements of the tarsier and the tree shrew within and in relation to primates
      may be incorrect because of convergence in these factors.

PMID- 15867429
TI  - Multi-species microarrays reveal the effect of sequence divergence on gene
      expression profiles.
AB  - Interspecies comparisons of gene expression levels will increase our
      understanding of the evolution of transcriptional mechanisms and help to identify
      targets of natural selection. This approach holds particular promise for apes, as
      many human-specific adaptations are thought to result from differences in gene
      expression rather than in coding sequence. To date, however, all studies directly
      comparing interspecies gene expression have been performed on single-species
      arrays, so that it has been impossible to distinguish differential hybridization
      due to sequence mismatches from underlying expression differences. To evaluate
      the severity of this potential problem, we constructed a new multiprimate cDNA
      array using probes from human, chimpanzee, orangutan, and rhesus. We find a large
      effect of sequence divergence on hybridization signal, even in the closest pair
      of species, human and chimpanzee. By comparing single-species array analyses with
      results from multispecies arrays, we examine how estimates of differential gene
      expression are affected by sequence divergence. Our results indicate that naive
      use of single-species arrays in direct interspecies comparisons can yield
      spurious results.

PMID- 15867430
TI  - Conservation of regulatory sequences and gene expression patterns in the
      disintegrating Drosophila Hox gene complex.
AB  - Homeotic (Hox) genes are usually clustered and arranged in the same order as they
      are expressed along the anteroposterior body axis of metazoans. The mechanistic
      explanation for this colinearity has been elusive, and it may well be that a
      single and universal cause does not exist. The Hox-gene complex (HOM-C) has been
      rearranged differently in several Drosophila species, producing a striking
      diversity of Hox gene organizations. We investigated the genomic and functional
      consequences of the two HOM-C splits present in Drosophila buzzatii. Firstly, we
      sequenced two regions of the D. buzzatii genome, one containing the genes labial
      and abdominal A, and another one including proboscipedia, and compared their
      organization with that of D. melanogaster and D. pseudoobscura in order to map
      precisely the two splits. Then, a plethora of conserved noncoding sequences,
      which are putative enhancers, were identified around the three Hox genes closer
      to the splits. The position and order of these enhancers are conserved, with
      minor exceptions, between the three Drosophila species. Finally, we analyzed the
      expression patterns of the same three genes in embryos and imaginal discs of four
      Drosophila species with different Hox-gene organizations. The results show that
      their expression patterns are conserved despite the HOM-C splits. We conclude
      that, in Drosophila, Hox-gene clustering is not an absolute requirement for
      proper function. Rather, the organization of Hox genes is modular, and their
      clustering seems the result of phylogenetic inertia more than functional
      necessity.

PMID- 15867431
TI  - Cell-free cotranslation and selection using in vitro virus for high-throughput
      analysis of protein-protein interactions and complexes.
AB  - We have developed a simple and totally in vitro selection procedure based on cell
      free cotranslation using a highly stable and efficient in vitro virus (IVV). Cell
      free cotranslation of tagged bait and prey proteins is advantageous for the
      formation of protein complexes and allows high-throughput analysis of protein
      protein interactions (PPI) as a result of providing in vitro instead of in vivo
      preparation of bait proteins. The use of plural selection rounds and a two-step
      purification of the IVV selection, followed by in vitro post-selection, is
      advantageous for decreasing false positives. In a single experiment using bait
      Fos, more than 10 interactors, including not only direct, but also indirect
      interactions, were enriched. Further, previously unidentified proteins containing
      novel leucine zipper (L-ZIP) motifs with minimal binding sites identified by
      sequence alignment as functional elements were detected as a result of using a
      randomly primed cDNA library. Thus, we consider that this simple IVV selection
      system based on cell-free cotranslation could be applicable to high-throughput
      and comprehensive analysis of PPI and complexes in large-scale settings involving
      parallel bait proteins.

PMID- 15867432
TI  - Target-selected mutant screen by TILLING in Drosophila.
AB  - The availability of the full Drosophila genomic DNA sequence prompts the
      development of a method to efficiently obtain mutations in genes of interest
      identified by their sequence homologies or biochemically. To date, molecularly
      characterized mutations have been generated in around 6000 of the approximately
      15,000 annotated fly genes, of which around one-third are essential for
      viability. To obtain mutations in essential and nonessential genes of interest,
      we took a reverse genetics approach, based on the large-scale detection of point
      mutations by Cel-I-mediated heteroduplex cleavage. A library of genomic DNA from
      2086 EMS-mutagenized lines was established. The library was screened for
      mutations in three genes. A total of 6.1 Mb were screened, and 44 hits were found
      in two different mutagenesis conditions. Optimal conditions yielded an average of
      one mutation every 156 kb. For an essential gene tested, five of 25 mutations
      turned out to cause lethality, confirming that EMS mutagenesis leads to high
      frequency of gene inactivation. We thereby established that Cel-I-mediated
      TILLING can be used to efficiently obtain mutations in genes of interest in
      Drosophila.

PMID- 15867433
TI  - Classification of a large microarray data set: algorithm comparison and analysis
      of drug signatures.
AB  - A large gene expression database has been produced that characterizes the gene
      expression and physiological effects of hundreds of approved and withdrawn drugs,
      toxicants, and biochemical standards in various organs of live rats. In order to
      derive useful biological knowledge from this large database, a variety of
      supervised classification algorithms were compared using a 597-microarray subset
      of the data. Our studies show that several types of linear classifiers based on
      Support Vector Machines (SVMs) and Logistic Regression can be used to derive
      readily interpretable drug signatures with high classification performance. Both
      methods can be tuned to produce classifiers of drug treatments in the form of
      short, weighted gene lists which upon analysis reveal that some of the signature
      genes have a positive contribution (act as "rewards" for the class-of-interest)
      while others have a negative contribution (act as "penalties") to the
      classification decision. The combination of reward and penalty genes enhances
      performance by keeping the number of false positive treatments low. The results
      of these algorithms are combined with feature selection techniques that further
      reduce the length of the drug signatures, an important step towards the
      development of useful diagnostic biomarkers and low-cost assays. Multiple
      signatures with no genes in common can be generated for the same classification
      end-point. Comparison of these gene lists identifies biological processes
      characteristic of a given class.

PMID- 15867434
TI  - Exploring relationships and mining data with the UCSC Gene Sorter.
AB  - In parallel with the human genome sequencing and assembly effort, many tools have
      been developed to examine the structure and function of the human gene set. The
      University of California Santa Cruz (UCSC) Gene Sorter has been created as a gene
      based counterpart to the chromosome-oriented UCSC Genome Browser to facilitate
      the study of gene function and evolution. This simple, but powerful tool provides
      a graphical display of related genes that can be sorted and filtered based on a
      variety of criteria. Genes may be ordered based on such characteristics as
      expression profiles, proximity in genome, shared Gene Ontology (GO) terms, and
      protein similarity. The display can be restricted to a gene set meeting a
      specific set of constraints by filtering on expression levels, gene name or ID,
      chromosomal position, and so on. The default set of information for each gene
      entry-gene name, selected expression data, a BLASTP E-value, genomic position,
      and a description-can be configured to include many other types of data,
      including expanded expression data, related accession numbers and IDs, orthologs
      in other species, GO terms, and much more. The Gene Sorter, a CGI-based Web
      application written in C with a MySQL database, is tightly integrated with the
      other applications in the UCSC Genome Browser suite. Available on a selected
      subset of the genome assemblies found in the Genome Browser, it further enhances
      the usefulness of the UCSC tool set in interactive genomic exploration and
      analysis.

PMID- 15867435
TI  - Begin at the beginning: predicting genes with 5' UTRs.
AB  - The retrainable, comparative gene predictor N-SCAN integrates multigenome
      modeling and 5' untranslated region (5' UTR) modeling. In this article, we
      evaluate N-SCAN's transcription-start site (TSS) and first exon predictions both
      computationally and experimentally. The computational results indicate that N
      SCAN is more accurate than any of the other tools we tested at predicting the TSS
      and the complete first exon. It is the only one of these tools that can predict
      complete gene structures together with 5' UTRs. Experimental evaluation shows
      that N-SCAN can be used to validate novel UTR introns in human gene predictions
      that do not overlap any RefSeq gene and even to correct RefSeq mRNAs by adding
      validated UTR exons that are missing from RefSeq.

PMID- 15867436
TI  - Genome-wide assembly and analysis of alternative transcripts in mouse.
AB  - To build a mouse gene index with the most comprehensive coverage of alternative
      transcription/splicing (ATS), we developed an algorithm and a fully automated
      computational pipeline for transcript assembly from expressed sequences aligned
      to the genome. We identified 191,946 genomic loci, which included 27,497 protein
      coding genes and 11,906 additional gene candidates (e.g., nonprotein-coding, but
      multiexon). Comparison of the resulting gene index with TIGR, UniGene, DoTS, and
      ESTGenes databases revealed that it had a greater number of transcripts, a
      greater average number of exons and introns with proper splicing sites per gene,
      and longer ORFs. The 27,497 protein-coding genes had 77,138 transcripts, i.e.,
      2.8 transcripts per gene on average. Close examination of transcripts led to a
      combinatorial table of 23 types of ATS units, only nine of which were previously
      described, i.e., 14 types of alternative splicing, seven types of alternative
      starts, and two types of alternative termination. The 47%, 18%, and 14% of 20,323
      multiexon protein-coding genes with proper splice sites had alternative
      splicings, alternative starts, and alternative terminations, respectively. The
      gene index with the comprehensive ATS will provide a useful platform for
      analyzing the nature and mechanism of ATS, as well as for designing the accurate
      exon-based DNA microarrays. The sequence data from this study have been submitted
      to GenBank under accession numbers: CK329321-CK334090; CF891695-CF906652;
      CF906741-CF916750; CK334091-CK347104; CK387035-CK393993; CN660032-CN690720;
      CN690721-CN725493.

PMID- 15867437
TI  - Elective ostial left main stenting: a tailored approach.
AB  - Elective left main (LM) stenting is increasingly performed as a valuable
      alternative to coronary artery bypass grafting. Nevertheless, clinical data are
      limited to registries, and randomized trials have not been published.
      Intravascular ultrasound (IVUS) has been recognized as an accurate tool for
      assessing optimal stent deployment. We hereby report the usefulness of IVUS in
      defining the interventional strategy in four consecutive patients presenting with
      severe, symptomatic ostial LM disease, and this in the era of drug-eluting
      stents. The first two patients were treated by a short drug-eluting stent for a
      critical LM stenosis as IVUS demonstrated a reference diameter < 3.7 mm. The
      third patient had a larger reference diameter and was treated with conventional
      stenting with optimization of the result by IVUS. IVUS was particularly helpful
      in all patients to confirm accurate stent placement in relation to the LM ostium
      and bifurcation. In another patient, based on IVUS findings, surgery was
      preferred. This patient with diabetes as a risk factor presented with comparable
      angiographic features. IVUS, however, showed diffuse disease without any healthy
      reference segment in the LM. All stented patients are asymptomatic at 15 +/- 7
      months follow-up with negative stress testing. The present observation indicates
      that IVUS is an essential tool for strategic selection and to optimize
      percutaneous coronary intervention for LM disease.

PMID- 15867438
TI  - Unprotected left main stenting: an alternative to CABG in a DES world?

PMID- 15867439
TI  - Evaluation of a simplified transseptal mitral valvuloplasty technique using over
      the-wire single balloons and complementary femoral and jugular venous approaches
      in 1,407 consecutive patients.
AB  - The over-the-wire double balloon technique (DBT) of balloon mitral valvuloplasty
      (BMV) has been decreasingly used in recent years because of its relative
      complexity and potential for left ventricular perforation. We attempted to make
      over-the-wire BMV simpler and safer by developing: (a) a single balloon technique
      (SBT) using a rapidly inflating, over-the-wire, cylindrical balloon having abrupt
      distal taper and short blunt tip to prevent left ventricular perforation, and (b)
      an alternative jugular approach to reduce technical difficulty in patients with
      cardiac anatomic distortion. SBT-BMV was evaluated over seven years in 1,407
      consecutive patients (femoral approach: 1,277 patients, jugular approach: 130
      patients), and compared with 954 patients who underwent DBT-BMV earlier at the
      same center. Results of SBT-BMV were comparable to those of DBT-BMV: optimal
      outcomes (91.0% versus 87.8%), fluoroscopy time (12.4 +/- 6.8 minutes versus 17.6
      +/- 7.2 minutes), significant right heart oxygen step-up (4.8% versus 10.7%), and
      major complication rates (3.7% versus 5.6%) were significantly better with SBT
      BMV; whereas mean post-BMV mitral valve area (1.92 +/- 0.31 cm2 versus 2.03 +/-
      0.42 cm2), and post-BMV hemodynamic parameters were inferior with SBT-BMV.
      Balloon-related left ventricular perforation did not occur in SBT-BMV.
      Fluoroscopy time in jugular approach SBT-BMV (9.0 +/- 4.2 minutes) was
      significantly lower than in the femoral approach SBT-BMV (12.4 +/- 6.8 minutes)
      despite cardiac anatomic distortion. SBT-BMV reduced procedural costs
      considerably. SBT-BMV was effective, safe, technically simple and economical; it
      was comparable to, and overcame several limitations of DBT-BMV.

PMID- 15867440
TI  - Routine transradial coronary angiography in unselected patients.
AB  - OBJECTIVES: To measure and compare the results of changing from routine
      transfemoral to routine transradial coronary angiography performed by a single
      operator. DESIGN: A learning period of 3 months for the transradial procedure
      with 43 selected patients was followed by a 12-month routine period with 243
      unselected patients. The success and complication rates, contrast volumes,
      catheter and X-ray times were measured and compared to results of a preceding
      period where the transfemoral approach was used. Follow-up was performed in the
      transradial groups 1.5-25 months after the procedure. RESULTS: Of the non
      selected patients, 9% were deemed unsuitable for the radial procedure. In the
      remaining 91% in which the transradial route was attempted, success was achieved
      in 91%. The complication rate was 2.7%. Increased operator experience reduces
      catheter and fluoroscopy times. At follow-up, 4.7% of the radial arteries were
      occluded, but the patients were without clinical sequelae. The occlusion rate was
      significantly higher with an unsuccessful procedure. CONCLUSIONS: Transradial
      coronary angiography can be performed safely and with acceptable image quality in
      non-selected patients after a learning period of 43 cases. Total procedure time
      is shorter than with the transfemoral approach. There were no bleeding
      complications and no procedure-related complications that required treatment.

PMID- 15867441
TI  - Use of a tacrolimus-eluting stent to inhibit neointimal hyperplasia in a porcine
      coronary model.
AB  - In-stent restenosis remains an unresolved problem which occurs in 5-20% of
      patients undergoing coronary stenting within the first 3-6 months. Neointimal
      formation is the main contributor to in-stent restenosis. Stent-induced arterial
      injury and peri-strut inflammation are involved in the process of neointimal
      formation by activating cytokines and growth factors which induce smooth muscle
      cell dedifferentiation, migration, and proliferation. Histopathological studies
      found that neointimal hyperplasia is principally composed of smooth muscle cells,
      inflammatory cells, and extracellular matrix. Stent-based delivery of anti
      proliferative and/or anti-inflammatory agents have shown beneficial effects on
      neointimal hyperplasia in experimental studies and clinical trials. Tacrolimus
      (FK506) is a water-insoluble macrolide immunosuppressant discovered in 1984. It
      has been widely used in reducing the incidence and severity of allograft
      rejection after organ transplantation. It has also been used to treat other
      inflammatory conditions such as atopic dermatitis. In this study, we evaluated
      the efficacy of stent-based delivery of tacrolimus on inflammation and neointimal
      formation in an overstretched coronary stent model.

PMID- 15867442
TI  - Preparedness of the cardiac catheterization laboratory for severe acute
      respiratory syndrome (SARS) and other epidemics.
AB  - Severe acute respiratory syndrome (SARS) is a highly contagious disease that has
      led to large hospital and community outbreaks, necessitating stringent infection
      control in its management. Among 90 SARS patients in our institution in the 2003
      outbreak, 2 underwent cardiac catheterization. We report the personal respiratory
      protection and environmental control measures implemented to minimize the risk of
      droplets spread during these procedures, including re-engineering of the
      ventilation system of the cardiac catheterization laboratory (CCL). The report
      highlights the importance of collaboration of CCL personnel with relevant
      hospital engineering and management teams to develop a contingency infection
      control plan to prepare for future outbreaks of SARS or other epidemics.

PMID- 15867443
TI  - SARS: so are you ready for safety?

PMID- 15867444
TI  - Cardiac cath lab activation by the emergency physician without prior consultation
      decreases door-to-balloon time.
AB  - OBJECTIVE: The purpose of this before-and-after study is to determine whether an
      ED strategy which calls for cardiac catheterization lab (cath lab) activation
      directly by the emergency physician (EP) is effective in decreasing door-to
      balloon time (DTBT). METHODS: In our active community teaching hospital ED, with
      an annual census of 55,000, the traditional practice for STEMI required
      cardiology consultation prior to cath lab notification. In November 2003 we
      instituted an ED protocol which mandated direct cath lab activation by the EP for
      eligible STEMI patients without prior notification of the cardiologist. We
      measured clinically relevant time intervals, including DTBT, prior to and after
      institution of the protocol. RESULTS: Twenty-four patients were enrolled after
      institution of the protocol; these were compared to twenty STEMI patients
      enrolled prior to the new protocol. DTBT decreased significantly, from 118 to 89
      minutes, p=.039. Other ED parameters, including door to exam (17 vs. 15 minutes)
      and total ED time (80 vs. 56 minutes, p = .056) decreased post-protocol but were
      not significantly different for the two periods. Those arriving by ambulance
      continued to have a significantly lower DTBT than non-ambulance patients (pre:
      change of 47 minutes, p = .03, post: change of 33 minutes; p = .012). Both groups
      were affected similarly by the change in protocol, decreasing DTBT by
      approximately 25%. CONCLUSION: We conclude that a strategy which mandates cath
      lab activation by the emergency physician for STEMI without prior cardiology
      consultation, reduces door to balloon time.

PMID- 15867445
TI  - Problems and complications of the transradial approach for coronary
      interventions: a review.

PMID- 15867446
TI  - Direct stenting and placement of a distal protection device after laser
      angioplasty in a saphenous vein graft with severe stenosis.

PMID- 15867447
TI  - Coronary artery stenting for acute myocardial infarction secondary to mild, blunt
      chest trauma in a soccer player.

PMID- 15867448
TI  - BlackAorta: a rare finding at aortic valve replacement.

PMID- 15867449
TI  - Cutting balloon entrapment during treatment of in-stent restenosis: an unusual
      complication and its management.

PMID- 15867450
TI  - Use of a second buddy wire during percutaneous coronary interventions: a simple
      solution for some challenging situations.
AB  - The buddy wire technique, i.e. the use of a second 0.014 inch guide wire placed
      alongside the one employed to advance balloons and stents inside the coronary
      artery during percutaneous coronary intervention (PCI), may help in a series of
      procedural challenges during PCI. Indeed, by improving both the stability of the
      guiding catheter and the support for balloon and stent, a buddy wire use is
      sometimes the simplest way to accomplish a successful procedure. In this paper,
      we discuss technical aspects of some specific circumstances frequently
      encountered during PCI, in which a buddy wire may be helpful. These include: 1)
      The reduction of balloon slippage during angioplasty for in-stent restenosis; 2)
      insufficient back-up of the guiding catheter; 3) stenting of lesions located in
      vessels with proximal tortuosities/angulations; 4) stenting of lesions distally
      located in the vessel; 5) facilitation in the positioning of distal protection
      devices; 6) stenting of a lesion distally located from a previously implanted
      stent or from a coronary segment with both calcification and sharp bend; 7) PCI
      on coronary arteries with anomalous origin. Because of its simplicity, low cost,
      and availability, the use of a buddy wire should be considered when dealing with
      the aforementioned conditions during PCI procedures.

PMID- 15867451
TI  - To pump or not to pump: a surgeon's view on randomization 25 years later.

PMID- 15867452
TI  - Self-fabricated covered stent to exclude an aortic aneurysm after balloon
      angioplasty for post-surgical recoarctation.

PMID- 15867453
TI  - Doppler evaluation and coil embolization of left internal mammary artery bypass
      graft side branch.

PMID- 15867454
TI  - A novel use for a distal embolic protection device: stent retrieval.

PMID- 15867455
TI  - A 40-year-old female with exertional angina.

PMID- 15867456
TI  - Percutaneous management of a saphenous venous graft leaking pseudoaneurysm.

PMID- 15867457
TI  - Delayed healing of a coronary artery plaque ulceration associated with acute
      myocardial infarction related to a paclitaxel-eluting stent.

PMID- 15867458
TI  - Catheter-induced spasm of the left main coronary artery due to anatomic "kinking"
      in its course.

PMID- 15867459
TI  - Twiddling to the extreme: development of twiddler syndrome in an implanted
      cardioverter-defibrilllator.

PMID- 15867460
TI  - Endovascular treatment of a stenosed anomalous left gastric artery: unique open
      artery of the gastrointestinal tract.

PMID- 15867461
TI  - Receptor databases and computational websites for ligand binding.

PMID- 15867462
TI  - Identification of orphan G protein-coupled receptor ligands using FLIPR assays.

PMID- 15867463
TI  - Quantitative analysis of orphan G protein-coupled receptor mRNAs by TaqMan Real
      Time PCR: G2A and GPR4 lysophospholipid receptor expression in leukocytes and in
      a rat myocardial infarction-heart failure model.

PMID- 15867464
TI  - mRNA: detection by in situ and northern hybridization.

PMID- 15867465
TI  - Radioligand-binding and molecular-imaging techniques for the quantitative
      analysis of established and emerging orphan receptor systems.

PMID- 15867466
TI  - Measurement of radioligand binding by scintillation proximity assay.

PMID- 15867467
TI  - Autoradiography of enzymes, second messenger systems, and ion channels.

PMID- 15867468
TI  - Immunocytochemical localization of receptors using light and confocal microscopy
      with application to the phenotypic characterization of knock-out mice.

PMID- 15867469
TI  - Live cell imaging of G protein-coupled receptors.

PMID- 15867470
TI  - Imaging and characterization of radioligands for positron emission tomography
      using quantitative phosphor imaging autoradiography.

PMID- 15867471
TI  - Dynamic in vivo imaging of receptors in small animals using positron emission
      tomography.

PMID- 15867472
TI  - Axillary cavernous lymphangioma in pregnancy and puerperium.
AB  - BACKGROUND: Cavernous lymphangioma is a form of benign congenital abnormality
      grouped under lymphatic malformations, which can clinically manifest as a cystic
      tumor. Common areas are the neck and axillary region. Most cases are diagnosed in
      children under the age of 2, and occasionally the diagnosis is made in utero.
      CASE: We present the case of a 29-year-old primigravid woman with an axillary
      cavernous lymphangioma which rapidly increased in size during pregnancy, and
      describe the treatment plan in this unusual situation. CONCLUSION: The treatment
      of a large lymphangioma during pregnancy has to be well planned, considering the
      welfare of the mother and baby. Most of the current therapies have never been
      tested in pregnant or lactating women. We discuss the possible pathomechanisms
      for the growth of lymphangioma during pregnancy with the overproduction of
      cytokines such as vascular endothelial growth factor.

PMID- 15867473
TI  - Expectation maximization algorithm based haplotype relative risk (EM-HRR): test
      of linkage disequilibrium using incomplete case-parents trios.
AB  - The Haplotype Relative Risk (HRR) was first proposed [Falk et al., Ann Hum Genet
      1987] to test for Linkage Disequilibrium (LD) between a marker and a putative
      disease locus using case-parent trios. Spurious association does not appear in
      such family-based studies under population admixture. In this paper, we extend
      the HRR to accommodate incomplete trios via the Expectation-Maximization (EM)
      algorithm [Dempster et al., J R Stat Soc Ser B, 1977]. In addition to triads and
      dyads (parent-offspring pair), the EM-HRR easily incorporates individuals with no
      parental genotype information available, which is excluded from the one parent
      Transmission/Disequilibrium Test (1-TDT) [Sun et al., Am J Epidemiol 1999]. Due
      to the data structure of EM-HRR, transmitted alleles are always available
      regardless of the number of missing parental genotypes. As a result of having a
      larger sample size, computer simulations reveal that the EM-HRR is more powerful
      in detecting LD than the 1-TDT in a population under Hardy-Weinberg Equilibirum
      (HWE). If admixture is not extreme, the EM-HRR remains more powerful. When a
      large degree of admixture exists, the EM-HRR performs better the 1-TDT when the
      association is strong, though not as well when the association is weak. We
      illustrate the proposed method with an application to the Framingham Heart Study.

PMID- 15867474
TI  - Developmental dyslexia--recurrence risk estimates from a german bi-center study
      using the single proband sib pair design.
AB  - OBJECTIVE: Several studies have demonstrated a genetic component for dyslexia.
      However, both segregation and linkage analyses show contradictory results
      pointing at the necessity of an optimal ascertainment scheme for molecular
      genetic studies. Previously, we have argued that the single proband sib pair
      design (SPSP) would be optimal. The aims of this paper therefore are to
      demonstrate the practicability of the SPSP design and the estimation of
      recurrence risks for reading and writing. METHODS: We assessed spelling and
      reading in a family sample ascertained through the SPSP design. 287 families with
      at least two siblings and their parents were recruited. At least one child was
      affected with spelling disorder according to a one standard deviation (1SD)
      discrepancy criterion. RESULTS: Mean values for probands and their siblings were
      different for both the spelling and the reading phenotype. For the probands,
      variances of the phenotype spelling were smaller. These effects became stronger
      with more extreme selection criteria. Both siblings fulfilled the 1SD criterion
      for spelling and reading in 60.3 and 28.9% of the families, respectively,
      indicating a low cost efficiency of the double proband sib pair approach. A
      recurrence risk of 4.52 (CI: 4.07-4.93) was obtained for spelling when the 1SD
      criterion was applied to both siblings. Recurrence risk estimates were similar
      for reading. CONCLUSION: The study demonstrates the suitability of the SPSP
      design for genetic analysis of dyslexia. The recurrence risk estimates may be
      used for determining sample sizes in gene mapping studies.

PMID- 15867475
TI  - Melanin aggregation and polymerization: possible implications in age-related
      macular degeneration.
AB  - The state of aggregation of the polymer melanin may determine its propensity to
      act either as an antioxidant or as a pro-oxidant. Age-related alterations in its
      state of aggregation are suggested to alter the degree of polymerization so as to
      confer increased pro-oxidant propensity to the melanin polymer. Degradative
      processes in/of melanosomes and lysosomes in the retinal pigment epithelium (RPE)
      appear to be intimately connected so that they may involve exchange of contents
      between these two organelles. An increased pro-oxidant environment inside
      lysosomes has been associated with preventing the digestion of cellular
      components including photoreceptor outer rod segments partly by altering function
      of lysosomal hydrolases. It is speculated that age-related accumulation of low
      molecular-weight phototoxic pro-oxidant melanin oligomers within lysosomes in the
      RPE may be partly responsible for decreasing the digestive rate of incorporated
      cellular components (including photoreceptor outer rod segments) which may lead
      to lipofuscin formation. More work is required to definitively refute or support
      such a hypothesis.

PMID- 15867476
TI  - Ascorbate in the rat lens: dependence on dietary intake.
AB  - PURPOSE: To establish a method for sample preparation to measure ascorbate in
      whole lenses and to investigate whether lens ascorbate concentration is dependent
      on dietary ascorbate intake. METHODS: Four groups of 3 young Sprague-Dawley rats
      each were fed chow containing L-ascorbate, either 0.0, 5.7, 57.0 or 114.0 mmol/kg
      for a duration of 4 weeks. Thereafter, each rat was sacrificed. The lens was
      extracted, photographed, and lens wet weight was measured. The lens was
      homogenized in 1.0 ml of 0.25% metaphosphoric acid, the homogenate was
      centrifuged and the supernatant ultrafiltered. The filtrate was injected into an
      ion exchange, reversed-phase Polypore H HPLC column equipped with a 254-nm
      ultraviolet detector. Samples were calibrated against an L-ascorbate standard.
      Polynomial regression analysis was performed on the data. RESULTS: All lenses
      were devoid of cataract. A 95% confidence interval for baseline content of
      ascorbate without any dietary intake was estimated to be 0.16+/-0.01 micromol/g
      wet weight of lens. The lens ascorbate concentration increased linearly with
      dietary ascorbate intake with an increased rate, estimated as a 95% confidence
      interval of 0.33+/-0.18 (micromol ascorbate) (g lens)-1)(mol ascorbate)-1 (kg
      chow) with r2=0.62. CONCLUSION: Lens ascorbate concentration linearly increases
      with dietary ascorbate intake without cataract development in the rat. The
      currently presented method for sample preparation to measure the whole-lens
      content of ascorbate is applicable.

PMID- 15867477
TI  - Influence of intracerebroventricular administration of histaminergic drugs on
      morphine state-dependent memory in the step-down passive avoidance test.
AB  - The effects of histaminergic drugs on morphine state-dependent memory of a
      passive avoidance task were examined in mice. Pre-training administration of
      morphine (5 mg/kg) led to state-dependent learning with impaired memory recall on
      the test day which was reversed by pre-test administration of the same dose of
      the opioid. The pre-test intracerebroventricular (i.c.v.) administration of the
      H(1) blocker (pyrilamine) prevented the restoration of memory by morphine. The
      H(2) blocker (ranitidine) was ineffective in this regard and the H(3) blocker
      (clobenpropit) potentiated the effect of morphine on memory recall. The pre-test
      i.c.v. administration of histamine alone (5, 10, and 20 microg/mouse) not only
      mimicked the effect of pre-test morphine treatment, but also increased this
      action of the opioid. The effect of histamine on memory recall was not changed by
      the pre-test administration of mu-opioid receptor antagonist, naloxone. In
      conclusion, the improvement of memory recall by morphine treatment, on the test
      day, seems to be, at least in part, through the release of histamine followed by
      the stimulation of H(1) receptors. Histamine by itself, when administered on the
      test day, mimicked morphine-induced memory improvement by a mechanism independent
      of the mu-opioid receptors.

PMID- 15867478
TI  - Expression of chemokine receptors in human gastric cancer.
AB  - The roles of chemokine receptors in cancer metastatic processes continue to draw
      research attention. Here we evaluated the expression profiles of the chemokine
      receptors CCR7 and CXCR4 in gastric cancer, and their potential use as prognostic
      markers. The expressions of CCR7 and CXCR4 mRNA were analyzed by RT-PCR in 10
      human gastric cancer cell lines and in 43 gastric cancer tissues, and in an
      additional 307 gastric cancer tissues by immunohistochemistry.
      Clinicopathological features and the prognoses of patients were also evaluated
      versus the expression of these two cytokine receptors. CCR7 and CXCR4 mRNA were
      found to be expressed in all gastric cancer cell lines, whereas their mRNA
      expression rates in gastric cancer tissues were 83.7% (36/43) and 100% (43/43),
      respectively. Immunohistochemical staining of the 307 gastric cancer tissues
      showed that the expression rates of CCR7 and CXCR4 were 22.5% (69/307) and 36.5%
      (112/307), respectively. Multivariate analysis of the immunohistochemistry
      results showed that the expression rate of CCR7 was significantly higher in
      differentiated than in undifferentiated gastric cancertypes (35.1 vs. 15.3%,
      p<0.001), and that CXCR4 was expressed at a higher rate in intestinal cancer than
      in diffuse-type cancer (58.8 vs. 22.3%, p<0.001). However, in contrast to
      previous studies, the expressions of CCR7 or CXCR4 were not associated with lymph
      node metastasis. Moreover, the prognosis of patients with CCR7-positive tumors
      was better than that of patients with CCR7-negative tumors, but no such
      correlation was observed for CXCR4 expression. In conclusion, the expressions of
      the chemokine receptors CCR7 and CXCR4 were found to be high in differentiated
      and intestinal-type gastric cancers, respectively.

PMID- 15867479
TI  - VEGF and its receptors (flt-1 and KDR/flk-1) as prognostic indicators in
      endometrial carcinoma.
AB  - Vascular endothelial growth factor (VEGF) is associated with increased
      angiogenesis and aggressive tumour growth. We investigated the expression and
      clinical significance of VEGF and its receptors, flt-1 and KDR/flk-1, in patients
      with uterine endometrial carcinoma. The series consisted of 115 endometrioid
      endometrial adenocarcinoma patients with FIGO stage I-IV. Additionally, samples
      from 3 patients with adenoacanthoma and 12 patients with poor prognostic variants
      of endometrial carcinoma were examined. Immunohistochemical assessment was
      classified as negative or positive based on staining intensity. The median follow
      up time of patients with endometrioid endometrial adenocarcinoma was 87 months.
      In endometrioid endometrial carcinomas, the positive immunostaining rate was 39%
      for VEGF, 65% for flt-1 and 68% for KDR/flk-1. There was a significant
      correlation between VEGF and both its receptors. Furthermore, this receptor
      expression was correlated between the two types of receptors. VEGF-, flt-1- and
      KDR/flk-1-positive immunostainings were not related to poor prognosis. We
      conclude that VEGF, flt-1 and KDR/flk-1 expressions are not useful prognostic
      markers for overall survival in patients with endometrioid endometrial carcinoma.

PMID- 15867480
TI  - Clinicopathological features and outcome of surgical treatment of 149 patients
      with early (pT1) gastric cancer.
AB  - BACKGROUND: Controversy exists concerning the definition of, treatment approach
      to, prognostic factors of and survival data on early gastric cancer. PATIENTS AND
      METHODS: 149 patients who underwent curative gastrectomy for carcinoma between
      1972 and 2002 and were classified as having early gastric cancer (T1Nany) were
      included into a retrospective study. Patients were followed for a median of 5.5
      years. RESULTS: We observed an increase in the incidence of early gastric cancer
      from 7.7% in the 1970s to 22.2% in the 1990s. None of the patients with mucosal
      tumors had lymph node metastases while 18 (20%) submucosal tumors were node
      positive. Multivariate analysis of all patients identified depth of tumor
      infiltration as the only independent risk factor for lymph node metastases. The
      analysis has shown that none of the clinicopathological features are reliable
      predictors of nodal status in patients with submucosal invasion. Patients with
      early gastric cancer had a very good prognosis, 10-year disease-specific survival
      was 80% or more in all subgroups of patients except for node-positive tumors.
      Depth of the tumor invasion, lymph node status as well as sex were found to be
      independent prognostic factors for overall survival. CONCLUSIONS: Early gastric
      cancer has a very good prognosis after standard surgery. Our data support the use
      of conservative limited surgical procedures for appropriate patients with mucosal
      gastric cancer. Patients with submucosal lesions require the same treatment
      approach as those with more advanced gastric cancer unless clinical usefulness of
      sentinel lymph node biopsy will be established.

PMID- 15867481
TI  - Interleukin-2 gene expression is a new biological prognostic marker in
      hepatocellular carcinomas.
AB  - BACKGROUND: Cytokines produced by tumor cells and tumor-infiltrating lymphocytes
      (TIL) appear to regulate tumor cell growth. The present study analyzed the
      correlation between local immune responses and cytokine gene expression levels in
      patients with primary hepatocellular carcinoma (HCC). MATERIAL AND METHODS: The
      gene expression levels of interleukin-2 (IL-2) and -12 (IL-12) were evaluated
      quantitatively by real-time reverse transcriptase polymerase chain reaction (RT
      PCR) and compared with the density of CD8+ TIL detected by immunohistochemistry
      in 59 surgically resected HCCs. RESULTS: IL-2 gene expression was detected in 33
      (56%) and IL-12 gene expression in 39 (66%) of 59 HCCs. Tissue infiltrating CD8+
      T lymphocytes in tumors were significantly suppressed compared with noncancerous
      liver tissues. The CD8+ T cell density of tumors with IL-2 gene expression was
      higher than that of tumors without IL-2 gene expression (p = 0.002). However,
      such a correlation was not detected in tumors with or without expression of IL-12
      genes. Patients with IL-2 positive tumors had a favorable prognosis. IL-2 gene
      expression was detected as an important prognostic factor independent of tumor
      stage. CONCLUSIONS: These findings indicate that in HCCs, tumor-infiltrating CD8+
      T cells might be activated by IL-2 produced by TIL and IL-2 gene expression in
      tumors may be an important prognostic biomarker in HCC.

PMID- 15867482
TI  - Evaluation of pain caused by urethrocystoscopy in patients with superficial
      bladder cancer: a perspective of quality of life.
AB  - AIM: The aim of this study is to evaluate patients' tolerance to pain caused by
      urethrocystoscopy (UCS) in both diagnosis and the period of follow-up in patients
      with superficial bladder cancer, and to evaluate these results with respect to
      quality of life. PATIENTS AND METHODS: Between March 2003 and October 2004, 66
      patients with bladder cancer or hematuria underwent UCS and recorded their
      overall pain level. RESULTS: The mean age was 60.4 (range 26-83) years. UCS was
      done only one time in 22 patients for the diagnosis of etiology of hematuria and
      was done 4 times in 44 patients every 3 months for bladder cancer follow-up. The
      mean pain scores on first, second, third, and fourth UCS were 4.3+/-2.2, 4.7+/
      2.5, 4.68+/-2.45, and 5.1+/-2.5, respectively. Statistically significant
      differences were found among mean pain scores of patients on first, third, and
      forth cystoscopic examinations (p < 0.05). No correlation was found between age
      and pain scores in this study group (p > 0.05). CONCLUSION: UCS is a painful
      surgical procedure and pain tolerance was not observed on repeated UCS. Therefore
      urologists need to use more effective anesthetic methods to provide better
      patients' tolerance to pain and quality of life during the endoscopic procedure.

PMID- 15867483
TI  - Preoperative radio-chemotherapy treatment in locally advanced rectal carcinoma.
      Results of 8-year follow-up.
AB  - BACKGROUND: Preoperative radio-chemotherapy (RCT) may play an important role in
      decreasing local recurrence and possibly improving survival for patients with
      advanced rectal carcinoma. PATIENTS AND METHODS: Between 1995 and 1998 we treated
      30 patients (pts) (median age 61.5 years) with advanced low rectal cancer.
      Radiotherapy was administered using a 10-MV linear accelerator delivering a total
      dose of 45 Gy to the pelvis over 5 weeks. 5-FU (500 mg/m2/d i.v.) was given
      concomitantly on days 1-3 and 29-31. Surgery was performed 2-4 weeks after RCT
      and included abdomino-perineal resection (APR) in 15 pts, anterior resection in
      11 pts, transanal resection in 1 pt, and explorative laparotomy in 1 pt; 2 pts
      refused surgery. RESULTS: There were no serious toxicities associated with RCT.
      Mild to moderate transient radiation dermatitis was noted in 3 pts, and grade II
      diarrhea in 4 pts. Postoperative pathologic staging was as follows: no tumor
      found (CR): 4 pts, MAC B1 (T2N0M0): 5 pts, MAC B2 (T3N0M0): 17 pts, B3 (vaginal
      involvement): 1 pt, MAC C2 (T3N1M0): 2 pts, and MAC D: 1 pt. Necrosis and/or
      fibrosis was noted as a prominent histopathologic feature. CONCLUSION:
      Preoperative RCT in this series of 30 pts with advanced rectal cancer was well
      tolerated and associated with a high response rate (13% CR, 17% PR, 57% NC). 5
      year overall survival was 70%, and 8-year survival was 58%.

PMID- 15867484
TI  - Prognostically favorable abdominal breast cancer metastases with stomach
      involvement.
AB  - BACKGROUND: Abdominal metastases with stomach involvement are rare in breast
      cancer. The median disease free interval from the time of breast cancer diagnosis
      to gastric metastasis is usually very long. Treatment is generally palliative,
      and expected survival time is less than 1 year. CASE REPORT: A 59-year-old woman
      with breast cancer developed diffuse abdominal metastases involving stomach,
      abdominal lymph nodes, and omentum 9 years after she underwent mastectomy and
      adjuvant chemotherapy. The histopathologic diagnosis found by stomach specimen
      examination was invasive lobular carcinoma, and the cells expressed high levels
      of estrogen and progesterone receptors. The abdominal metastases were treated
      with surgery, postoperative chemotherapy, and further hormonal therapy. This was
      successful, and the patient has been in remission for more than 3 years.
      CONCLUSION: Once the definitive diagnosis of breast cancer metastases to the
      abdomen including the stomach is established, treatment that targets systemic
      breast cancer must be initiated. Our patient's extended survival time suggests
      that surgical treatment could be considered for selected patients.

PMID- 15867485
TI  - Combination of anti-estrogenic therapy with radiation in breast cancer:
      simultaneous or sequential treatment?
AB  - Adjuvant radiotherapy and adjuvant endocrine therapy are commonly given to
      patients with invasive breast cancer or with ductal carcinoma in situ (DCIS).
      Although both therapies have been well established through a number of randomized
      studies, little is known about a possible interaction of both treatment
      modalities if they are given simultaneously. A number of in vitro studies
      indicated that tamoxifen treatment might reduce the intrinsic radiosensitivity of
      MCF-7 breast cancer cells. Conversely, estradiol treatment increased the
      intrinsic radiosensitivity of MCF-7 cells. This phenomenon has not been found in
      clinical studies. Retrospective analyses of prospectively randomized clinical
      studies did not indicate an antagonistic effect of tamoxifen on the effectiveness
      of ionizing radiation (XRT), since local control has been consistently higher
      when XRT was combined with tamoxifen, compared to treatment with XRT alone,
      regardless of whether tamoxifen was started simultaneously with radiotherapy or
      after completion of radiotherapy. Currently there are no clinical data available
      that would suggest an adverse effect of adjuvant tamoxifen treatment started
      prior to or simultaneously with radiotherapy in breast cancer or DCIS. However,
      since an antagonistic effect of tamoxifen and simultaneous chemotherapy has been
      reported recently, the issue of simultaneous.

PMID- 15867486
TI  - Clinical significance of VEGF-A, -C and -D expression in esophageal malignancies.
AB  - Vascular endothelial growth factors (VEGF)-A, -C and -D are members of the
      proangiogenic VEGF family of glycoproteins. VEGF-A is known to be the most
      important angiogenic factor under physiological and pathological conditions,
      while VEGF-C and VEGF-D are implicated in the development and sprouting of
      lymphatic vessels, so called lymphangiogenesis. Local tumor progression, lymph
      node metastases and hematogenous tumor spread are important prognostic factors
      for esophageal carcinoma (EC), one of the most lethal malignancies throughout the
      world. We found solid evidence in the literature that VEGF expression contributes
      to tumor angiogenesis, tumor progression and lymph node metastasis in esophageal
      squamous cell carcinoma (SCC), and many authors could show a prognostic value for
      VEGF-assessment. In adenocarcinoma (AC) of the esophagus angiogenic properties
      are acquired in early stages, particularly in precancerous lesions like Barrett's
      dysplasia. However, VEGF expression fails to give prognostic information in AC of
      the esophagus. VEGF-C and -D were detected in SCC and dysplastic lesions, but not
      in normal mucosa of the esophagus. VEGF-C expression might be associated with
      lymphatic tumor invasion, lymph node metastases and advanced disease in
      esophageal SCC and AC. Therapeutic interference with VEGF signaling may prove to
      be a promising way of anti-angiogenic co-treatment in esophageal carcinoma.
      However, concrete clinical data are still pending.

PMID- 15867488
TI  - Antiretroviral therapies for treatment-experienced patients: current status and
      research challenges.

PMID- 15867489
TI  - Loss of reactivity of vaccine-induced CD4 T cells in immunized monkeys after
      SIV/HIV challenge.
AB  - BACKGROUND: Immunization protocols involving priming with DNA and boosting with
      recombinant live virus vectors such as recombinant modified Vaccinia Ankara
      (rMVA) are considered as vaccine candidates against HIV. Such protocols improve
      the outcome of simian/human immunodeficiency virus (SHIV) pathogenic challenge in
      Rhesus monkeys. OBJECTIVES: To investigate the fate of vaccine-induced T cells
      after a mucosal SHIV challenge. METHODS: We immunized Rhesus monkeys (Macaca
      mulatta) by DNA priming followed by rMVA boost. After intrarectal challenge with
      SHIV 89.6P, immunized animals demonstrated early control of viral replication and
      stable CD4 T-cell counts. We monitored T-cell responses by measuring IFN-gamma
      secretion and proliferation. RESULTS: Immunization induced strong and sustained
      SHIV-specific CD4 and CD8 T-cell responses. CD8 T-cell responses were recalled
      during acute infection, whereas none of the vaccine-induced SHIV-specific CD4 T
      cell responses were recalled. Moreover, most of the CD4 T-cell responses became
      undetectable in peripheral blood or lymph nodes even after in-vitro peptide
      stimulation. In contrast, we persistently detected CD4 T-cell responses specific
      for control recall antigens in infected animals. CONCLUSION: SHIV 89.6P challenge
      results in a lack of reactivity of vaccine-induced SHIV-specific CD4 T cells.
      These results may have important implications in the AIDS vaccine field,
      especially for the evaluation of new vaccine candidates, both in preventive and
      therapeutic trials.

PMID- 15867491
TI  - Characterization of humoral and cell-mediated immune responses directed against
      hepatitis C virus F protein in subjects co-infected with hepatitis C virus and
      HIV-1.
AB  - BACKGROUND: Hepatitis C virus (HCV) F protein is encoded in an alternate reading
      frame overlapping the core protein region. Its precise sequence, biological
      function and mode of expression are currently unclear. This study was conducted
      to examine the prevalence and characteristics of host humoral and cell-mediated
      immune responses directed against F protein in patients co-infected with HCV and
      HIV-1. METHODS: Mutations were introduced to allow the expression of HCV-1a F
      protein in the absence of core. This recombinant and a truncated form lacking the
      first 11 amino acid residues shared with core were expressed in Escherichia coli,
      and their amino acid sequences were verified by mass spectrometry. Vaccinia-F
      protein recombinants were used to test F protein-specific cytotoxic T lymphocyte
      (CTL) activity. The binding of F protein-derived peptides to HLA-A*0201 was
      studied to identify putative CTL epitopes. RESULTS: Sera from 23 of 39 patients
      infected with various HCV genotypes recognized the truncated form, including 13
      of 25 subjects co-infected with HIV-1, indicative of antigenic crossreactivity
      and consistent with the conservation of F protein coding sequences between HCV
      genotypes. Crossreactive F protein-specific CTL precursors were detected in nine
      of 11 HCV-infected subjects, including seven of nine patients co-infected with
      HCV and HIV-1. Finally, three novel putative HLA-A*0201-restricted CTL epitopes
      were identified. CONCLUSION: These results indicate that patients co-infected
      with HCV and HIV-1 can mount immunoglobulin and CTL responses directed against
      HCV F protein that are fully comparable in scope and magnitude with those
      observed in individuals infected with HCV alone.

PMID- 15867490
TI  - Antigen-specific immune responses and liver histology in HIV and hepatitis C
      coinfection.
AB  - OBJECTIVE: To test the hypothesis that antigen-specific interferon (IFN)gamma
      responses are correlated with milder liver disease in subjects coinfected with
      HIV-1 and hepatitis C virus (HCV). DESIGN: Cellular immune responses were studied
      in a cohort with HIV/HCV coinfection (n = 107) who underwent liver biopsy.
      METHODS: We measured HCV-specific and recall responses in peripheral blood
      mononuclear cells using IFNgamma and interleukin (IL)-10 ELISpots, and correlated
      these immune responses with liver histology. The relationship of immunologic,
      virologic and clinical variables to inflammation and fibrosis was modeled using
      recursive partitioning. RESULTS: There were significant negative correlations
      between inflammatory scores and IFNgamma production in response to the HCV
      proteins core, NS5 and summed HCV responses. Lower fibrosis scores were also
      correlated with higher IFNgamma production in response to NS5 and summed HCV
      proteins. Higher IFNgamma production in response to Candida was significantly
      associated with lower inflammatory and fibrosis scores. In multivariable models,
      factors associated with severe fibrosis were lower IFNgamma responses to Candida
      and summed HCV proteins. Factors associated with severe inflammation were
      detectable HIV viral load and lower HCV viral load, while predictors of mild
      inflammation included undetectable HIV viral load and higher IFNgamma response to
      Candida. CONCLUSIONS: In this cohort of subjects coinfected with HIV and HCV,
      antigen-specific IFNgamma responses are correlated with milder inflammation and
      fibrosis. Immunological responses best predicted severity of fibrosis, while
      clinical variables and recall antigen responses best predicted severity of
      inflammation.

PMID- 15867492
TI  - High levels of HPV-16 DNA are associated with high-grade cervical lesions in
      women at risk or infected with HIV.
AB  - OBJECTIVE: To examine associations between levels of episomal and integrated
      human papillomavirus (HPV) 16 DNA and the grade of cervical disease. DESIGN:
      Cross-sectional data were obtained from a cohort of women with and without HIV
      infection and with high-risk sexual behaviour. METHODS: Episomal and integrated
      HPV-16 DNA loads were measured in cervicovaginal lavages collected from 75 women
      (58 HIV seropositive, 17 HIV seronegative) using real-time polymerase chain
      reaction assays, controlling for cell content and the presence of inhibitors.
      RESULTS: HPV-16 viral loads were significantly higher in women with high-grade
      squamous intraepithelial lesions (n = 6) than in women with normal cytology (n =
      44), whether total (10(8.28) versus 10(5.10) HPV-16 DNA copies/microg DNA),
      episomal (10(7.99) versus 10(4.61)) or integrated (10(7.95) versus 10(4.77)) HPV
      16 viral loads were measured (P < 0.02 for each comparison). Thirty-nine women
      had colposcopy [11 normal cervix, 16 cervical intraepithelial neoplasia (CIN) 1,
      six CIN 2, six CIN 3] and 24 additional women had three consecutive normal
      cytology smears. Controlling for age, race, CD4 cell count and HIV status, total
      (OR 3.5, 95% CI 1.2-10.4; P = 0.02), episomal (OR 2.9, 95% CI 1.2-7.4; P = 0.02,)
      and integrated (OR 1.6, 95% CI 1-2.6; P = 0.05) HPV-16 DNA loads were
      significantly associated with CIN 2,3, but the differences between CIN 1 and CIN
      2,3 were not significant (P > 0.06). A greater amount of cellular DNA was
      collected from women with CIN 2,3 (P = 0.007). CONCLUSION: Higher HPV-16 DNA
      loads are associated with cervical lesions detected by either histology or
      cytology. No additional information is gained by measuring integrated or episomal
      over total HPV-16 DNA loads.

PMID- 15867493
TI  - Nelfinavir and nevirapine side effects during pregnancy.
AB  - BACKGROUND: The risk of vertical transmission of HIV has been substantially
      reduced since the introduction of highly active antiretroviral therapy (HAART);
      however, the impact of taking HAART during pregnancy on the woman, the fetus and
      the infant is not yet understood. OBJECTIVE: To assess and compare tolerability,
      safety and efficacy of nelfinavir- or nevirapine-containing HAART in a cohort of
      pregnant and non-pregnant HIV-infected women in The Netherlands. DESIGN:
      Retrospective comparative study. METHODS: In 15 centres specializing in HIV in
      The Netherlands, data on patient characteristics, HAART, adverse events, viral
      load response, mode of delivery and HIV status of the neonate were obtained from
      medical records of HIV-infected pregnant women who received HAART during
      pregnancy between January 1997 and June 2003. These data were compared with a
      control group of HIV-infected non-pregnant women that was obtained from the Dutch
      HIV-monitoring foundation database. RESULTS: Data from 186 pregnant and 186 non
      pregnant HIV-infected women using a nelfinavir- or nevirapine-containing regimen
      were analysed. The pregnant women were younger, used a nelfinavir containing
      regimen more often, had higher CD4 cell counts and lower HIV RNA levels.
      Nelfinavir-related gastrointestinal symptoms (P < 0.001), hyperglycaemia (P <
      0.001) and nevirapine-related hepatotoxicity (P = 0.003) occurred more often
      during pregnancy. The risk of nevirapine-induced rash was not increased. No major
      adverse events occurred. CONCLUSION: Nelfinavir- or nevirapine-containing HAART
      regimens during pregnancy are well tolerated. Side effects of antiretroviral
      therapy are more frequent in pregnant than in non-pregnant women.

PMID- 15867494
TI  - Severity and outcome of HIV-associated Pneumocystis pneumonia containing
      Pneumocystis jirovecii dihydropteroate synthase gene mutations.
AB  - BACKGROUND: The impact of Pneumocystis jirovecii (formerly P. carinii)
      dihydropteroate synthase (DHPS) gene mutations on morbidity and mortality of
      Pneumocystis pneumonia (PCP) in HIV-positive patients is unclear. OBJECTIVE: To
      determine whether severity and outcome of HIV-associated PCP differs according to
      DHPS genotype. SETTING: A prospective, observational study in a university
      affiliated county hospital. PATIENTS: The study included 197 patients with 215
      microscopically confirmed PCP episodes and successfully sequenced DHPS genotypes;
      175 (81%) episodes displayed mutant genotypes. MAIN OUTCOME MEASURE: All-cause
      mortality within 60 days. RESULTS: The majority of patients (86%) with PCP
      containing Pneumocystis DHPS mutations survived. Although severity of PCP was
      comparable, there was a trend for more patients with mutant genotypes than
      patients with wild-type to require mechanical ventilation (14.3% versus 2.5%; P =
      0.056) and to die (14.3% versus 7.5%, P = 0.31). Independent predictors of
      mortality at baseline were low serum albumin levels [odds ratio (OR), 4.62; 95%
      confidence interval (CI), 1.63-13.1; P = 0.004] and requiring intensive care
      within 72 h of hospitalization (OR, 5.06; 95% CI, 1.43-18.0; P = 0.012).
      CONCLUSION: The majority of HIV-infected patients with PCP containing mutant
      Pneumocystis DHPS genotypes survived. Mortality was related primarily to the
      underlying severity of illness. However, a trend towards increased mortality in
      episodes of PCP containing mutant DHPS genotypes was observed and this warrants
      further study.

PMID- 15867495
TI  - Couple-focused support to improve HIV medication adherence: a randomized
      controlled trial.
AB  - OBJECTIVE: To assess the efficacy of a couple-based intervention to improve
      medication-taking behavior in a clinic population with demonstrated adherence
      problems. DESIGN: A randomized controlled trial (SMART Couples Study) conducted
      between August 2000 and January 2004. SETTING: Two HIV/AIDS outpatient clinics in
      New York City. PARTICIPANTS: Heterosexual and homosexual HIV-serodiscordant
      couples (n = 215) in which the HIV-seropositive partner had < 80% adherence at
      baseline. The sample was predominantly lower-income racial/ethnic minorities.
      INTERVENTION: Participants were randomly assigned to a four-session couple
      focused adherence intervention or usual care. The intervention consisted of
      education about treatment and adherence, identifying adherence barriers,
      developing communication and problem-solving strategies, optimizing partner
      support, and building confidence for optimal adherence. OUTCOME MEASURES:
      Medication adherence at week 8 (2 weeks after the intervention) compared with
      baseline, assessed with a Medication Event Monitoring System cap. RESULTS:
      Intervention participants showed higher mean medication adherence at post
      intervention when compared with controls whether adherence was defined as
      proportion of prescribed doses taken (76% versus 60%) or doses taken within
      specified time parameters (58% versus 35%). Also, participants in the
      intervention arm were significantly more likely to achieve high levels of
      adherence (> 80%, > 90%, or > 95%) when compared with controls. However, in most
      cases, effects diminished with time, as seen at follow-up at 3 and 6 months.
      CONCLUSION: The SMART Couples program significantly improved medication adherence
      over usual care, although the level of improved adherence, for many participants,
      was still suboptimal and the effect was attenuated over time.

PMID- 15867496
TI  - Declining risk of triple-class antiretroviral drug failure in Danish HIV-infected
      individuals.
AB  - OBJECTIVES: To analyse the incidence, prevalence, and predictors for development
      of triple-class antiretroviral drug failure (TCF) in individuals infected with
      HIV. DESIGN: Population-based observational cohort study from 1 January 1995 to
      31 December 2003, focusing on all 2722 recipients of highly active antiretroviral
      therapy (HAART) in Denmark. METHODS: We used person-years analysis, Kaplan-Meier
      survival curves and Cox regression analysis. TCF was defined as a minimum of 120
      days with viral load > 1000 copies/ml on treatment with each of the three major
      drug classes. RESULTS: We observed 177 TCFs, yielding a crude incidence rate (IR)
      of 1.8 per 100 person-years [95% confidence interval (CI), 1.6-2.1]. Seven years
      after initiation of HAART, 17.2% (95% CI, 14.5-20.5) of antiretroviral (ART)
      experienced patients, but only 7.0% (95% CI, 4.3-11.2) of ART-naive patients were
      estimated to have failed. After an initial rise, the IR from the third to the
      sixth year of HAART declined significantly for ART-experienced patients
      [incidence rate ratio (IRR), 0.80 per year (95% CI, 0.66-0.97); P = 0.022], and
      non-significantly for ART-naive patients [IRR, 0.79 per year (95% CI, 0.53-1.18);
      P = 0.255]. The IR for all patients being followed each year declined from 1997
      to 2003 [IRR, 0.88 (95% CI, 0.81-0.96); P = 0.002]. The prevalence of TCF
      remained stable at less than 7% after 2000. Predictors of TCF at commencement of
      HAART were a CD4 cell count below 200, a previous AIDS-defining event, previous
      antiretroviral exposure, earlier year of HAART initiation, and young age.
      CONCLUSIONS: The risk of TCF is declining in Denmark and the prevalence remains
      stable.

PMID- 15867497
TI  - Using prevalence data from the programme for the prevention of mother-to-child
      transmission for HIV-1 surveillance in North Uganda.
AB  - OBJECTIVES: To validate the use of data from a programme for the prevention of
      mother-to-child transmission (PMTCT) in estimating HIV-1 prevalence in North
      Uganda. METHODS: The study was conducted at St. Mary's Hospital Lacor. We
      compared the estimated prevalence for 3580 attendees at the antenatal clinic who
      were selected for anonymous surveillance to that for 6785 pregnant women who
      agreed to undergo voluntary counselling and testing (VCT) for enrolment in the
      PMTCT programme. Log-binomial regression models were used to identify the factors
      associated with both VCT uptake and HIV-1 infection, which could bias the
      prevalence estimates based on PMTCT data. RESULTS: In 2001-2003, the age
      standardized prevalence was similar (11.1% in the anonymous surveillance group
      and 10.9% in the VCT group). The estimates were also similar when compared for
      each year tested. Analogously, no important differences were observed in age
      specific prevalence. Of the factors associated with HIV-1 infection, only time of
      residence at current address [prevalence proportion ratio (PPR) = 1.05; 95%
      confidence interval (CI), 1.00-1.10], marital status (PPR = 1.05; 95% CI, 1.01
      1.10) and partner's occupation (PPR = 1.05; 95% CI, 1.01-1.10) were associated
      with VCT uptake, yet the associations were weak. CONCLUSIONS: The prevalence
      estimated based on the VCT data collected as part of the PMTCT programme could be
      used for HIV-1 surveillance in North Uganda. At the national level, however, it
      needs to be evaluated whether PMTCT data could replace, or instead be combined
      with, the data from sentinel surveillance.

PMID- 15867498
TI  - Evolution of resistance mutations pattern in HIV-1-infected patients during
      intensification therapy with a boosted protease inhibitor.
AB  - Intensification therapy adding a boosted protease inhibitor (PI) to a failing
      regimen has the potential to worsen the resistance profile. Sixty-six patients
      included in four different boosted PI intensification studies were assessed and
      resistance mutations in the reverse transcriptase and protease genes were
      evaluated at baseline and 4 weeks after the initiation of the intensification
      strategy. Only one of the 66 patients developed changes in their pattern of
      mutations able to generate or increase resistance to new drugs.

PMID- 15867499
TI  - Influence of the R22H variant of macrophage inflammatory protein 1beta/Lag-1 in
      HIV-1 survival.
AB  - The chemokine macrophage inflammatory protein 1beta/CCL4, ligand of the major HIV
      co-receptor CCR5, is encoded by two genes, Act-2 and Lag-1. Our work focused on
      R22H, a variant of Lag-1 located near the N-loop, in the 310 turn, a domain
      essential for interacting with CCR5. We observed that HIV-1-infected patients
      from the SEROCO cohort, bearing the R22H variant either at the homozygous or
      heterozygous state, exhibit a worse global survival compared with wild-type
      homozygous individuals.

PMID- 15867500
TI  - Reintroduction of the 2G12 epitope in an HIV-1 clade C gp120.
AB  - Many clade C isolates of HIV-1 do not react with monoclonal antibody (MAb) 2G12,
      a broad-ranging human neutralizing MAb that recognizes high mannose carbohydrate
      groups attached to glycoprotein gp120. We reintroduced a partial and complete
      2G12 epitope into a clade C background, HIV-1(CN54), and examined the antibody
      reactivity of the resulting recombinant molecules. Two glycosylation sites
      recovered 2G12 binding completely, but some binding was evident after the
      reintroduction of a single glycosylation site at Asn295.

PMID- 15867501
TI  - In vitro suppression of latent HIV-1 activation by vitamin E: potential clinical
      implications.
AB  - We evaluated the effect of vitamin E in controlling HIV-1 production upon
      activation of the patients' reservoir of resting CD4 lymphocytes in tissue
      culture experiments. The addition of vitamin E to patients' cultures resulted in
      significantly reduced levels of p24 virus production (P = 0.0015). These results
      suggest that vitamin E supplementation may interfere with the emergence of drug
      resistant HIV-1 variants archived in the resting cell reservoir and delay or
      limit virus rebound upon treatment interruptions.

PMID- 15867502
TI  - Impact of accessing methadone on the time to initiating HIV treatment among
      antiretroviral-naive HIV-infected injection drug users.
AB  - We examined the impact of methadone maintenance therapy (MMT) on subsequent
      antiretroviral therapy (ART) use in a prospective cohort of injection drug users.
      At 24 months after enrollment, the rate of ART use was 69.7% among those who were
      on MMT at baseline and 44.4% among those not on MMT (log-rank P = 0.001). In a
      Cox model, the use of MMT was independently associated with an elevated rate of
      ART use.

PMID- 15867503
TI  - Switching from protease inhibitors to a single-class regimen of
      abacavir/lamivudine/zidovudine plus tenofovir in patients with HIV load
      suppression.

PMID- 15867504
TI  - In vivo replication kinetics of a nef-deleted strain of HIV-1.

PMID- 15867505
TI  - Fanconi syndrome associated with didanosine therapy.

PMID- 15867506
TI  - Should cotrimoxazole prophylaxis be taken by all adults with HIV in Africa?

PMID- 15867507
TI  - The sage within: celebrate nurses week by talking with some wise nurses.

PMID- 15867508
TI  - Retaining the recruited: a shift in focus may make all the difference.

PMID- 15867510
TI  - Breastfeeding.

PMID- 15867511
TI  - Breastfeeding.

PMID- 15867514
TI  - Breastfeeding.

PMID- 15867528
TI  - Is there a doctor nurse in the house? A new vision for advanced practice nursing.

PMID- 15867529
TI  - Human rabies: unusual cases shine the spotlight on an old disease.

PMID- 15867530
TI  - Indwelling urinary catheters: common mechanical and pathogenic problems.

PMID- 15867531
TI  - My dad has Parkinson disease: and my mother has boundless love.

PMID- 15867532
TI  - Family presence: making room.

PMID- 15867534
TI  - Caring for patients on mechanical ventilation: what research indicates is best
      practice.

PMID- 15867536
TI  - An end to angels.

PMID- 15867537
TI  - The quality of care provided in nursing homes: nurses can help facilities do the
      right things.

PMID- 15867544
TI  - Bold new world: technology should ease nurses' jobs, not create a greater
      workload.

PMID- 15867545
TI  - Reducing pediatric medication errors: children are especially at risk for
      medication errors.

PMID- 15867547
TI  - Setting nurse-patient ratios: ANA bill calls for development of staffing systems
      in hospitals.

PMID- 15867549
TI  - Nurses Improving Care for Health System Elders (NICHE).

PMID- 15867550
TI  - Rising above: New Jersey ICU RNs work together to create art.

PMID- 15867551
TI  - Preparing for disasters: helping yourself as you help others.

PMID- 15867552
TI  - Intralesional corticosteroid injection versus extracorporeal shock wave therapy
      for plantar fasciopathy.
AB  - OBJECTIVE: To compare the efficacy of low-energy extracorporeal shock wave
      therapy (ESWT) and intralesional corticosteroid injection (CSI) for the treatment
      of plantar fasciopathy present for at least 6 weeks. DESIGN: A prospective,
      randomized, controlled, observer-blinded study over a period of 12 months.
      SETTING: Primary care and hospital setting. PATIENTS: A total of 132 patients
      were enrolled in the study, and 125 completed the study. Nineteen nonrandomized
      patients acted as a surrogate control group. INTERVENTIONS: All patients
      performed a standardized Achilles tendon and plantar fascia stretching program.
      The patients were randomly allocated to either treatment group A or B. Group A
      received a single CSI, while group B were referred for a course of low-dose ESWT
      comprising 3 treatments over a period of 3 weeks. Group C consisted of 19
      nonrandomized patients who performed the standardized stretching program only.
      MAIN OUTCOME MEASUREMENTS: The worst daily pain recorded on a visual analogue
      scale (VAS), and the tenderness at the plantar fascia insertion as determined by
      an algometer. These measures were recorded immediately prior to the commencement
      of treatment and 3 months and 12 months posttreatment. RESULTS: With regard to
      VAS pain scores, values for the CSI (1.48; 0-7) were significantly lower than
      both ESWT (3.69; 0-8), and controls (3.58; 2-5) at 3 months. At 12 months, VAS
      scores for CSI (0.84; 0-7) and ESWT (0.84; 0-4) were both significantly lower
      than controls (2.42; 1-4). The tenderness values at 3 months were significantly
      higher for CSI (9.42; 7-11) than both ESWT (6.72; 4-11) and controls (7.63; 6-9).
      P < 0.05 was used throughout. CONCLUSIONS: Corticosteroid injection is more
      efficacious and multiple times more cost-effective than ESWT in the treatment of
      plantar fasciopathy that has been symptomatic for more than 6 weeks.

PMID- 15867553
TI  - Growth status and estimated growth rate of youth football players: a community
      based study.
AB  - OBJECTIVE: To characterize the growth status of participants in community
      sponsored youth football programs and to estimate rates of growth in height and
      weight. DESIGN: Mixed-longitudinal over 2 seasons. SETTING: Two communities in
      central Michigan. PARTICIPANTS: Members of 33 youth football teams in 2 central
      Michigan communities in the 2000 and 2001 seasons (Mid-Michigan PONY Football
      League). METHODS: Height and weight of all participants were measured prior to
      each season, 327 in 2000 and 326 in 2001 (n = 653). The body mass index (kg/m)
      was calculated. Heights and weights did not differ from season to season and
      between the communities; the data were pooled and treated cross-sectionally.
      Increments of growth in height and weight were estimated for 166 boys with 2
      measurements approximately 1 year apart to provide an estimate of growth rate.
      MAIN OUTCOME MEASURE: Growth status (size-attained) of youth football players
      relative to reference data (CDC) for American boys and estimated growth rate
      relative to reference values from 2 longitudinal studies of American boys.
      RESULTS: Median heights of youth football players approximate the 75th
      percentiles, while median weights approximate the 75th percentiles through 11
      years and then drift toward the 90th percentiles of the reference. Median body
      mass indexes of youth football players fluctuate about the 85th percentiles of
      the reference. Estimated growth rates in height approximate the reference and may
      suggest earlier maturation, while estimated growth rates in weight exceed the
      reference. CONCLUSION: Youth football players are taller and especially heavier
      than reference values for American boys. Estimated rates of growth in height
      approximate medians for American boys and suggest earlier maturation. Estimated
      rates of growth in weight exceed those of the reference and may place many youth
      football players at risk for overweight/obesity, which in turn may be a risk
      factor for injury.

PMID- 15867554
TI  - Cumulative incidence of achilles tendon rupture and tendinopathy in male former
      elite athletes.
AB  - OBJECTIVE: To study the cumulative incidence of Achilles tendon rupture and
      tendinopathy among former top-level athletes. DESIGN: Historical cohort study.
      SETTING: Finland. PARTICIPANTS: Male former elite athlete cohort members (n =
      785; median age, 69 years when responding to the questionnaire; range, 54-97) and
      their matched controls (n = 416; median age, 68 years; range, 56-94). OUTCOME
      MEASUREMENTS: Questionnaire-reported Achilles tendinopathy and tendon rupture
      diagnosed by physicians before the age of 45 years and within the subjects'
      lifetimes. RESULTS: Cumulative incidence of Achilles tendinopathy before the age
      of 45 was high for middle and long-distance runners (adjusted odds ratio, 31.2
      compared with controls; P < 0.001), and cumulative incidence of Achilles tendon
      rupture was high for sprinters (odds ratio, 14.9; P < 0.001). CONCLUSIONS:
      Achilles tendon problems seem to constitute clinically significant and common
      problems in specific sports.

PMID- 15867555
TI  - Effects of ball sports on future risk of stress fracture in runners.
AB  - OBJECTIVE: To evaluate whether playing ball sports during childhood and
      adolescence is associated with the risk of stress fractures in runners later in
      life. DESIGN: Retrospective cohort study. SETTING: National track and field
      championships, held at Stanford University. PARTICIPANTS: One hundred fifty-six
      elite female and 118 elite male distance runners, age 18 to 44 years.
      INTERVENTIONS: A 1-page questionnaire was used to collect data regarding ages
      during which athletes played basketball and soccer, as well as other important
      covariates and outcomes. OUTCOME MEASUREMENTS: Athletes reported the ages when
      stress fractures occurred. Time to event was defined as the number of years from
      beginning competitive running to the first stress fracture or to current age, if
      no fracture had occurred. RESULTS: In both men and women, playing ball sports in
      youth correlated with reduced stress fracture incidence later in life by almost
      half, controlling for possible confounders. In men, each additional year of
      playing ball sports conferred a 13% decreased incidence of stress fracture
      (adjusted hazard ratio [HR] and 95% confidence interval, 0.87 [0.79-0.95]. Among
      women with regular menses, the HR for each additional year of playing ball sports
      was similar: 0.87 (0.75-1.00); however, there was no effect of length of time
      played among women with irregular menses (HR, 1.03 [0.92-1.16]). In men, younger
      ages of playing ball sports conferred more protection against stress fractures
      (HR for each 1-year-older age at first exposure, 1.29 [1.14, 1.45]). CONCLUSIONS:
      Runners who participate during childhood and adolescence in ball sports may
      develop bone with greater and more symmetrically distributed bone mass, and with
      enhanced protection from future stress fractures.

PMID- 15867556
TI  - Skatepark-related injuries in a southern California skatepark and their
      associated short-term disability and healthcare utilization.
AB  - OBJECTIVE: To assess the types of injuries, the extent of short-term disability,
      and the degree of healthcare utilization in skatepark-injured patients. DESIGN:
      The study design was a prospective case series with 1-year follow-up. SETTING:
      Level I trauma center and emergency department located in Orange, California.
      PARTICIPANTS: Subjects age 7 years or older who sustained an injury at a local
      skatepark and were treated in our emergency department were included in the
      study. Ninety-five subjects were enrolled with a total of 97 injury encounters.
      MAIN OUTCOME MEASUREMENTS: Types of injuries, extent of short-term disability,
      degree of healthcare utilization. RESULTS: Emergency department diagnoses
      included 57 fractures, 6 dislocations, 15 strains/sprains/contusions, 7
      lacerations, 2 dental fractures, 9 head injuries, and 1 intra-abdominal injury.
      Nine of the emergency department encounters terminated in admission to the
      hospital. The peak sum of time lost from school, work, parental time lost from
      work, and specialist visits were found to occur at 1 month postinjury. Similarly,
      the number of postinjury follow-up medical visits peaked at the 1-month interval.
      Subject disability was largely categorized as moderate initially, with a
      subsequent reduction to no disability by the 9th postinjury month. CONCLUSION:
      Skatepark-related injuries can yield substantial time lost from school and work,
      considerable short-term disability, and an increase in healthcare resource
      utilization.

PMID- 15867557
TI  - Women hydrate more than men during a marathon race: hyponatremia in the Houston
      marathon: a report on 60 cases.
AB  - OBJECTIVE: To examine the relationship between gender and the development of
      hyponatremia in marathon runners. DESIGN: A retrospective analysis of prerace and
      postrace data collected on 117 runners completing the Houston Marathon from 2000
      to 2003. SETTING: The Houston Marathon. PARTICIPANTS: A total of 117 marathon
      runners (63 male and 54 female) who consented to participate in hyponatremia
      research. MAIN OUTCOME MEASURES: Prerace and postrace body weight and serum
      sodium ([Na+]) concentrations were measured. Total fluid intake was self-reported
      immediately following the race. RESULTS: : Of the runners tested, 28% developed
      hyponatremia ([Na+] < or = 135 mmol/L). Hyponatremic runners (n = 33) drank
      significantly more fluid (31.70 versus 18.90 cups; P < 0.001), lost the least
      weight (-0.14 versus -1.61 kg; P < 0.001), and dropped serum [Na+] levels further
      (-7.48 versus -1.92; P < 0.001) compared with nonhyponatremic runners. Female
      runners (n = 54) were significantly lighter (62.46 versus 80.73 kg; P < 0.001),
      ran slower (303.02 versus 269.06 minutes; P < 0.001), lost the least weight (
      0.62 versus -1.68 kg; P < 0.001), dropped serum [Na+] levels further (-4.44
      versus -2.67; P < 0.01), and had lower postrace serum [Na+] values (136.87 versus
      138.50; P < 0.01) compared with male runners while consuming the same total
      amount of fluid during the race (22.87 versus 22.30 cups; P = 0.83, NS). There
      were significant inverse relationships between serum [Na+] change versus body
      weight change (r = -0.65; P < 0.001) and between postrace [Na+] versus body
      weight change (r = -0.60; P < 0.001), with significant sex differences noted only
      between nonhyponatremic female and male runners (-0.91 versus -0.2.05 kg; P <
      0.001) and between hyponatremic and nonhyponatremic male runners (-0.11 versus 
      2.05 kg; P < 0.001). CONCLUSIONS: Female marathon runners drink more fluid than
      male runners in proportion to body size. A loss of 3 kg body weight corresponds
      to a 0 change in serum [Na+] from prerace to postrace, suggesting that a loss of
      3 kg during a marathon represents euhydration and not dehydration. All cases of
      hyponatremia reported in this study are a result of overhydration based on this
      convention.

PMID- 15867558
TI  - Effect of noncustom bimolar mouthguards on peak ventilation in ice hockey
      players.
AB  - OBJECTIVE: To examine the effect of a noncustom bimolar mouthguard on ventilation
      in female varsity ice hockey players. DESIGN: Prospective crossover study. MAIN
      OUTCOME MEASURES: Expired ventilation (VE), oxygen uptake (VO2), and heart rate
      were measured in 12 university varsity female ice hockey players while these
      players were skating on a skating treadmill. Data were collected for each player
      with and without a mouthguard at both submaximal and maximal efforts to recreate
      the intensity of games. RESULTS: VE and VO2 were similar (P > 0.05) with and
      without a noncustom bimolar mouthguard at submaximal effort. The mean VE at
      maximal effort (VEmax) was significantly lower (P < 0.05) using the mouthguard
      (108.5 l/min) compared with without a mouthguard (114.1 l/min). VO2 at maximal
      effort (VO2max) was significantly lower (P < 0.05) using the mouthguard (48.8
      mL.kg.min) compared with without a mouthguard (52.4 mL.kg.min). Heart rates were
      similar for players with and without a mouthguard at both submaximal and maximal
      efforts. CONCLUSIONS: Noncustom bimolar mouthguards may reduce ventilation and
      oxygen uptake at maximal efforts by female ice hockey players.

PMID- 15867559
TI  - Effects of high-intensity exercises on 13C-nandrolone excretion in trained
      athletes.
AB  - OBJECTIVE: Nandrolone is an anabolic steroid widely used in several sports. The
      numerous nandrolone positive cases in the recent years (International Olympic
      Committee statistics) led to several studies in the antidoping field.
      Nevertheless, essential questions pertaining to nandrolone endogenous production,
      the effects of physical exercise on the excretion of nandrolone metabolites, and
      contamination from nutritional supplements must still be addressed. The purpose
      of this study was to evaluate the influence of exhaustive exercises on 19
      norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) urinary excretion rates
      after administration of labeled nandrolone. SETTING AND PARTICIPANTS: A total of
      34 healthy male Caucasian volunteers from the Institute of Sports Sciences and
      Physical Education (University of Lausanne) applied to participate in the study.
      All subjects were free from any physical drug addiction and were instructed
      strictly to avoid any nutritional supplement or steroid before and during the
      study. The participants were randomly dispatched in 2 groups in a double-blind
      way: a placebo group and a group treated with C-labeled nandrolone. MAIN OUTCOME
      MEASUREMENTS: The urinary concentrations of the 2 main nandrolone metabolites, 19
      NA and 19-NE, were measured using gas chromatography coupled with mass
      spectrometry. In addition, clinical parameters such as creatinine, total protein,
      and beta2-microglobuline levels were determined using immunologic assays.
      RESULTS: After an oral ingestion of a 25 mg 3,4-C2-nandrolone dose, followed by a
      second identical dose 24 hours later, 19-NA and 19-NE could be detected in the
      urine for a period of 6 days after the initial intake. Despite several
      interesting observations, the measurements were very scattered and did not appear
      to be significantly influenced by exercise sessions in the athlete population.
      CONCLUSIONS: The results of this study suggest that physical exercise cannot be
      considered as a reliable parameter that systematically affects nandrolone
      metabolite concentrations in the urine.

PMID- 15867560
TI  - Females recruit quadriceps faster than males at multiple knee flexion angles
      following a weight-bearing rotary perturbation.
AB  - OBJECTIVE: To compare the effect of knee angle on muscle response times and
      neuromuscular recruitment patterns between sexes following a perturbation in
      single leg stance at 10 degrees, 20 degrees, and 30 degrees. We hypothesized that
      response times would be faster at lesser knee flexion angles and that females
      would recruit their quadriceps faster than males at all angles. DESIGN: A
      repeated-measures design. SETTING: Motion analysis laboratory. PARTICIPANTS:
      Twenty (10 female; 10 male) healthy, recreationally active volunteers.
      INTERVENTIONS: A rotary perturbation in single leg stance. OUTCOME MEASUREMENTS:
      Response times of the medial and lateral quadriceps, hamstrings, and
      gastrocnemius. RESULTS: There was a trend toward faster response times for all
      muscles closer toward extension. A consistent neuromuscular recruitment pattern
      for both males and females was evident for each knee angle tested. Females,
      however, contracted their quadriceps faster than males at all knee flexion
      angles. CONCLUSIONS: Small changes in knee angle near extension do not alter
      muscle response times and hence neuromuscular recruitment patterns in males and
      females. Regardless of knee flexion angle, following a perturbation in single leg
      stance, females contract their quadriceps faster than males. CLINICAL RELEVANCE:
      Earlier contraction of the quadriceps in females may increase anterior tibial
      translation and hence anterior cruciate ligament strain, thereby heightening
      injury risk.

PMID- 15867561
TI  - Effect of environmental temperature on shock absorption properties of running
      shoes.
AB  - OBJECTIVE: To determine the effect of temperature changes on the shock
      attenuation of 4 running shoe shock absorption systems. DESIGN: Prospective.
      SETTING: Motion analysis laboratory. INTERVENTIONS: The shock attenuation of 4
      different running shoes representing common shock absorption systems (Nike Air
      Triax, Asics Gel Nimbus IV, Adidas a3 cushioning, Adidas Supernova cushion) was
      measured at ambient temperatures of -20 degrees C, -10 degrees C, 0 degrees C,
      +10 degrees C, +20 degrees C, +30 degrees C, +40 degrees C, and +50 degrees C.
      Repeated-measures analysis of variance was used to determine differences between
      shoes. OUTCOME MEASURES: Shock attenuation as indicated by peak deceleration (g)
      measured by a mechanical impactor following ASTM Standard F1614-99. RESULTS:
      Shock attenuation decreased significantly with reduced temperature for each shoe
      tested. The Adidas a3 shoe exhibited significantly higher peak decelerations
      (lower shock attenuation) at cold temperatures compared with the other shoes.
      CONCLUSIONS: Cold ambient temperatures significantly reduce the shock attenuation
      of commonly used running shoes. These findings have important clinical
      implications for individuals training in extreme weather environments,
      particularly those with a history of lower limb overuse injuries.

PMID- 15867562
TI  - A pilot study of clinical agreement in cardiovascular preparticipation
      examinations: how good is the standard of care?
AB  - OBJECTIVE: To evaluate the interobserver agreement between physicians regarding a
      abnormal cardiovascular assessment on athletic preparticipation examinations.
      DESIGN: Cross-sectional clinical survey. SETTING: Outpatient Clinic, United
      States Military Academy, West Point, NY. PARTICIPANTS: We randomly selected 101
      out of 539 cadet-athletes presenting for a preparticipation examination. Two
      primary care sports medicine fellows and a cardiologist examined the cadets.
      INTERVENTIONS: After obtaining informed consent from all participants, all 3
      physicians separately evaluated all 101 cadets. The physicians recorded their
      clinical findings and whether they thought further cardiovascular evaluation
      (echocardiography) was indicated. MAIN OUTCOME MEASURES: Rate of referral for
      further cardiovascular evaluation, clinical agreement between sports medicine
      fellows, and clinical agreement between sports medicine fellows and the
      cardiologist. RESULTS: Each fellow referred 6 of the 101 evaluated cadets (5.9%).
      The cardiologist referred none. Although each fellow referred 6 cadets, only 1
      cadet was referred by both. The kappa statistic for clinical agreement between
      fellows is 0.114 (95% CI, -0.182 to 0.411). There was no clinical agreement
      between the fellows and the cardiologist. CONCLUSIONS: This pilot study reveals a
      low level of agreement between physicians regarding which athletes with an
      abnormal examination deserved further testing. It challenges the standard of care
      and questions whether there is a need for improved technologies or improved
      training in cardiovascular clinical assessment.

PMID- 15867563
TI  - Hip strength following hamstring tendon anterior cruciate ligament
      reconstruction.
AB  - OBJECTIVE: The objective of this study was to determine whether there is
      alteration in resultant joint moment of the hip extensors and adductors after
      hamstring anterior cruciate ligament (ACL) reconstruction. DESIGN: Cross
      sectional outcome analysis. SETTING: University sport medicine center. SUBJECTS:
      Fifteen subjects more than 1 year after ACL reconstruction with semitendinosus
      and gracilis tendons were compared with 15 matched controls with no knee injury.
      INTERVENTIONS: Strength testing of the hip extensors and hip adductors of both
      limbs. MAIN OUTCOME MEASUREMENTS: Isokinetic (50 degrees /s and 150 degrees /s)
      hip extensor strength test and isometric (15 degrees and 30 degrees ) hip
      adductor strength test. RESULTS: Hip extensors increase in strength after
      hamstring ACL reconstruction, evening out normal side-to-side strength
      differences. Hip adductor strength deficits of up to 43% are demonstrated in the
      ACL reconstructed subjects compared with controls. CONCLUSIONS: The
      identification of hip adductor strength deficits after hamstring harvest for ACL
      reconstruction may have important implications for both graft harvest site
      selection as well as postoperative rehabilitation protocols. Given the known
      existence of knee strength deficits after ACL reconstruction, increases in
      isovelocity hip extensor strength may contribute to increased lower limb strength
      imbalances. This may have implications for the ability of the lower limb muscles
      to protect the ACL graft.

PMID- 15867564
TI  - Effects of physical activity on exercise capacity in twins with alpha-1
      antitrypsin deficiency.

PMID- 15867565
TI  - Base of fourth metatarsal stress fracture: tendency for prolonged healing.

PMID- 15867566
TI  - Distal ulnar neuropathy in a golf player.
AB  - A 51-year-old right-handed amateur golfer has developed fasciculations in the
      left first dorsal interosseous muscle for 3 weeks. He did not have any pain or
      motor or sensory deficit. The nerve conduction study and electromyography showed
      that he had mononeuropathy of the deep palmar branch of the ulnar nerve in his
      left palm. The forceful grasp of golf club handle in the left palm contributes to
      this rare focal neuropathy. He was advised to change his grip on the golf club,
      and the symptom resolved almost immediately.

PMID- 15867567
TI  - Bilateral recurrent dislocation of the ulnar nerve in semiprofessional swimmer: a
      case report.

PMID- 15867568
TI  - Agreement statement from the 1st international rodeo research and clinical care
      conference: calgary, alberta, Canada (july 7-9, 2004).

PMID- 15867570
TI  - Re: Efficacy of celecoxib, a COX-2-specific inhibitor, and naproxen in the
      management of acute ankle sprain: results of a double-blind, randomized
      controlled trial.

PMID- 15867571
TI  - Shock-wave treatment for chronic lateral epicondylitis in recreational tennis
      players.

PMID- 15867572
TI  - 5-year follow-up of open or closed kinetic chain exercises for patellofemoral
      pain.

PMID- 15867573
TI  - Obesity, physical activity, and the risk of decline in health and mobility.

PMID- 15867574
TI  - The elderly "weekend warrior" and risk of mortality.

PMID- 15867575
TI  - The emergence of definitive hematopoietic stem cells in the mammal.
AB  - PURPOSE OF REVIEW: Hematopoietic stem cells (HSC) are the basis for blood
      formation during adult life. The amazing potency of HSCs has been exploited for
      over 30 years in regenerative therapies for patients with blood-related genetic
      disease and leukemia. As clinically important cells and also as the most widely
      studied cell differentiation system, they have been the focus of intense
      fundamental research. Indeed, HSC research has established many paradigms in the
      more general field of stem cells. Recently, the study of the embryonic origins of
      HSCs and their genetic program is beginning to provide unique insights into how
      these stem cells are formed, maintained, and expanded, and how they contribute to
      the complex adult hematopoietic system. Although many short-lived hematopoietic
      progenitors are present in early stage mammalian embryos, this review will focus
      on the events leading to emergence of the most potent cells of the hematopoietic
      system, HSCs and on their developmental lineage relationships. RECENT FINDINGS:
      Developmental and genetic studies further our understanding of the fate
      determination events occurring in several embryonic tissues leading to the
      generation of potent HSCs--those cells with the ability to long-term, high-level
      repopulate all hematopoietic lineages of the adult. SUMMARY: Several mammalian
      embryonic tissues contribute to the growth and/or generation of potent HSCs that
      are the source of blood cells throughout the lifespan of the individual. Insight
      into how mammalian HSC fate is determined has been provided through functional,
      phenotypic, and genetic studies at early developmental stages.

PMID- 15867576
TI  - Genetic networks that regulate B lymphopoiesis.
AB  - PURPOSE OF REVIEW: The B cell developmental pathway represents a leading model
      within the hematopoietic system for the analysis of genetic networks, which
      orchestrate cell fate specification and commitment. Considerable progress is
      being achieved in the characterization of regulatory components that comprise
      such networks and examining their connectivity. These components include the
      cytokine receptors Flk2 and IL-7R as well as the transcription factors PU.1,
      Ikaros, Bcl11a, E2A, EBF, and Pax-5. Based on new experimental evidence, a
      comprehensive model is proposed that invokes sequentially acting and inter
      dependent regulatory modules that instruct the generation of B cell precursors
      from multipotential hematopoietic progenitors. RECENT FINDINGS: The transcription
      factor PU.1 regulates the generation of lymphoid progenitors that express Flk2
      and IL-7R. IL-7R receptor signaling appears to function in specification of the B
      cell fate. The transcription factor EBF can bypass the requirement for PU.1 and
      E2A in early B cell development. Pax-5 expression and function are contingent on
      EBF. SUMMARY: Assembly of gene regulatory networks involved in cell fate
      specification may facilitate the efficient and directed generation of lineage
      specific hematopoietic progenitors from embryonic stem cells for therapeutic
      purposes.

PMID- 15867577
TI  - Hox regulation of normal and leukemic hematopoietic stem cells.
AB  - PURPOSE OF REVIEW: Herein we focus on recent studies of knock out mice that
      demonstrate a function for the clustered homeobox (Hox) genes in normal
      hematopoiesis, on papers that point to their general involvement in human
      leukemia, and discuss the advances in the understanding of the mechanisms
      underlying their role in these processes. RECENT FINDINGS: Expression analysis
      and gain- or loss- of function studies have shown that Hox play an important role
      in the regulation of early stages of hematopoiesis, including the self-renewal of
      hematopoietic stem cells (HSCs)/early progenitors. In the area of leukemia,
      numerous models of murine leukemia have demonstrated a role for Hox in the
      pathobiology of the disease. Moreover, the identification of multiple Hox genes
      as partners of chromosomal translocations and the observed global deregulation of
      Hox genes and cofactors demonstrated by gene profiling of cells from leukemic
      patients, have unequivocally shown a major function for Hox genes and cofactors
      in a wide spectrum of human leukemia. SUMMARY: The identification of Hox genes as
      HSC regulators has been exploited to develop strategies to efficiently expand
      HSCs ex vivo, a key step to the success of therapies based on HSC transplantation
      and the understanding of mechanisms underlying HSC regulation. As leukemia is the
      result of deregulation of normal HSC development, the elucidation of the role of
      Hox in the pathobiology of the disease is helping to understand how HSCs self
      renew and differentiate, and moreover, should facilitate the development of
      strategies for the management of leukemia.

PMID- 15867578
TI  - The specification of early hematopoiesis in the mammal.
AB  - PURPOSE OF REVIEW: A number of interesting surprises has emerged during the past
      year in the field of early hematopoietic development. This review highlights
      recent studies that have challenged the prevailing view of embryonic and fetal
      hematopoiesis in mammals, with a focus on the mouse as a model system. The
      authors apologize to the many colleagues whose work could not be cited because of
      space limitations. RECENT FINDINGS: Advances in our understanding of the
      embryonic origins of hematopoiesis in mammals and in the regulation of primitive
      and definitive hematopoietic development are discussed. SUMMARY: The ontological
      relation between primitive (embryonic) and definitive (fetal and adult)
      hematopoiesis still holds some mysteries for the biologist. Both technical and
      conceptual breakthroughs have refined our view of how blood cells form at
      different stages of development. What we learn from the embryo is not only of
      fundamental interest but may have future applications in the clinic.

PMID- 15867579
TI  - Bibliography. Current world literature. Hematopoiesis.

PMID- 15867580
TI  - A new oral delivery system for 5-ASA: preliminary clinical findings for MMx.
AB  - BACKGROUND: Multi-matrix (MMx), a new delivery system for mesalazine, seems to
      release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This
      study had 2 objectives: (1) to evaluate the therapeutic response to MMx in
      patients with active left-sided disease and (2) to gain additional insights as to
      how the therapy would compare with topical 5-ASA. METHODS: Patients received
      either 1.2 g of 5-ASA MMx three times per day plus placebo enema or 4 g of 5-ASA
      enema plus placebo tablets for 8 weeks. The primary endpoint was clinical
      remission (clinical activity index < or =4) at 8 weeks. Secondary endpoints were
      endoscopic and histologic remissions. RESULTS: Seventy-nine patients were
      enrolled. Clinical remission rates at 4 and 8 weeks were 57.5% and 60.0% for
      patients treated with MMx and 68.4% and 50.0% for patients randomized to 5-ASA
      enemas, respectively (95% confidence interval for the difference at 8 weeks, -12
      to +32). Endoscopic remission was achieved by 45.0% of patients on 5-ASA MMx and
      by 36.8% of those on enema, whereas 15.0% and 8% of patients, respectively,
      showed histologic remission. Compliance was 97.0% for oral and 87.5% for topical
      therapy. In the enema group, compliance was 88.0% for the patients in remission
      and 65.5% for those with active disease. CONCLUSIONS: Preliminary studies suggest
      that similar rates for induction of remission can be expected from 5-ASA enemas
      and MMx for patients with left-sided ulcerative colitis.

PMID- 15867581
TI  - Endoscopic factors in the diagnosis of colorectal dysplasia in chronic
      inflammatory bowel disease.
AB  - BACKGROUND: Surveillance colonoscopy in inflammatory bowel diseases (IBDs) is
      advocated for early diagnosis of neoplasia but is imperfect because some patients
      develop cancer despite surveillance. We sought to determine if any endoscopic
      factors during surveillance colonoscopy were associated with the diagnosis of
      colorectal dysplasia before the development of cancer. METHODS: We reviewed the
      Mayo Clinic endoscopic database and medical records of patients with IBD who
      underwent surveillance colonoscopy between January 2002 and November 2003.
      Associations were sought between endoscopic factors and the diagnosis of
      dysplasia. Among 635 IBD patients, 24 (3.8%) had flat dysplasia and 12 (1.9%) had
      IBD-related polypoid dysplasia. In 28 patients (4.4%), sporadic tubular adenoma
      was identified. Colonoscopies in which flat dysplasia was identified varied in
      duration from 7 to 81 minutes (median, 24.5 min) compared with 3 to 70 minutes
      (median, 22 min) for those in which dysplasia was not found. RESULTS: Using
      logistic regression analysis, we found that every additional minute in total
      colonoscopy time increased the flat dysplasia diagnosis rate by 3.5% (P =
      0.0157). There was a significant correlation between median surveillance
      colonoscopy duration per endoscopist and flat dysplasia diagnosis rate (P =
      0.0066). The number of biopsies taken during the procedures with flat dysplasia
      ranged from 6 to 36 (median, 28) compared with 2 to 54 (median, 25) in those
      without flat dysplasia. There was no significant effect of biopsy number of
      dysplasia diagnosis. CONCLUSIONS: Our results show that the practice of
      surveillance colonoscopy varies greatly among endoscopists, and longer procedure
      duration is significantly associated with the likelihood of dysplasia diagnosis.

PMID- 15867582
TI  - Effect of recombinant growth hormone treatment on children with Crohn's disease
      and short stature: a pilot study.
AB  - BACKGROUND: Growth failure frequently complicates Crohn's disease in childhood.
      Abnormalities in the growth hormone (GH)/insulin-like growth factor-1 axis may
      occur. The effects of administered GH on growth have not been studied previously
      in a randomized trial. METHODS: Seven children (6 boys and 1 girl; age, 11.9-16
      yr) with Crohn's disease and growth failure were enrolled. In phase 1, patients
      were randomized to either GH (0.05 mg/kg per day) or placebo; in phase 2,
      patients who received placebo during the first year received GH for various time
      periods. Follow-up was every 3 months for up to 2 years. RESULTS: During placebo
      treatment (4 patients), mean height-for-age z score (haz) increased 0.23 in the
      first half year and 0.55 in the second half year. The mean improvement in haz
      during the first half year of GH treatment (7 patients) was 0.13; during the
      second half year (5 patients), haz decreased 0.01. Effects of GH varied among
      patients; 2 patients grew only when nutritional supplementation was added.
      Observed changes were not statistically significant; however, the number of
      patients studied was small, and statistical analyses could have been affected by
      sample size. Serum insulin-like growth factor-1 levels correlated with height
      velocity. Only 2 patients later reached expected adult height. CONCLUSIONS: In
      this pilot study, GH treatment at the dose given did not stimulate growth in
      children with Crohn's disease and short stature. Whether or not GH plus
      nutritional therapy would be effective in promoting sustained catch-up growth
      remains to be determined.

PMID- 15867583
TI  - Premedication and infusion reactions with infliximab: results from a pediatric
      inflammatory bowel disease consortium.
AB  - BACKGROUND: Infusion reactions (IRs) are the most common adverse events
      associated with the use of infliximab for inflammatory bowel disease (IBD).
      Antipyretics, antihistamines, and corticosteroids have been used to prevent the
      development of IRs, but their efficacy is not known. We studied the proportion of
      pediatric patients receiving infliximab for IBD that developed IRs and the
      potential effects of premedication on IR. METHODS: Uniformly collected data from
      a cohort of pediatric patients with IBD enrolled between January 2000 and May
      2003 at 6 pediatric centers were analyzed. Data were retrospectively reviewed and
      analyzed. RESULTS: A total of 1652 infusions given to 243 patients in 6 centers
      was analyzed. Overall, 60 IRs were recorded in 40 patients (3.6% of infusions,
      16.5% of patients). Thirty-three of 243 patients received premedication before
      the first IR (group 1). Two hundred ten patients did not receive premedication
      until the development of IRs, if at all (group 2). IRs were more common among
      patients in group 1 than in group 2 (12/33 versus 28/210, P < 0.01). Of the 28
      patients in group 2 with IRs, 10 began receiving premedication with each
      subsequent infusion, 12 continued without premedications, and 6 had no further
      infusions recorded. Two of 10 who began receiving premedication had a subsequent
      IR versus 6 of 12 who did not receive premedication (P = 0.15). CONCLUSIONS: IRs
      occur in a small proportion of infusions among pediatric patients receiving
      infliximab for IBD. Premedication does not seem to prevent the development of
      IRs; however, once an IR has occurred, premedication may be indicated to prevent
      subsequent IRs.

PMID- 15867584
TI  - Probiotic therapy in the prevention of pouchitis onset: decreased interleukin
      1beta, interleukin-8, and interferon-gamma gene expression.
AB  - BACKGROUND: Probiotic therapy has been shown to prevent the onset of pouchitis
      and to improve the quality of life in ulcerative colitis patients who required
      ileal pouch anal anastomosis. Pouchitis has been associated with elevated levels
      of proinflammatory cytokines and chemokines. METHODS: In this retrospective
      analysis of archived endoscopic samples from responding patients enrolled in the
      above-mentioned trial, we were interested in studying mucosal gene expression of
      the pleiotropic proinflammatory cytokines (interleukin-1beta, interleukin-6), TH1
      cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-12),
      regulatory cytokines (interleukin-10, transforming growth factor-beta), and the
      chemokine interleukin-8. In addition to assessment of cytokine gene expression,
      the presence of polymorphonuclear cells in the mucosal tissue was evaluated.
      RESULTS: Data show that patients who were treated with probiotics had significant
      lower mucosal mRNA expression levels of interleukin-1beta, interleukin-8, and
      interferon-gamma compared with placebo-treated patients. In addition, a lower
      number of polymorphonuclear cells was present in the tissue of patients within
      the probiotic group compared with the number of polymorphonuclear cells in the
      tissue of patients receiving placebo and patients having an episode of pouchitis.
      CONCLUSIONS: These data suggest that probiotic treatment regulates the mucosal
      immune response by reducing mucosal levels of neutrophil-chemoattractant IL-8 and
      tissue influx of polymorphonuclear cells, and may further act by inhibition of T
      cell activation, by reinforcement of barrier function and by a tight control of
      the potent pro-inflammatory cytokine IL-1beta.

PMID- 15867585
TI  - Nonpathogenic Escherichia coli strain Nissle1917 prevents murine acute and
      chronic colitis.
AB  - BACKGROUND: Nonpathogenic Escherichia coli strain Nissle1917 has been used as a
      probiotics in human inflammatory bowel disease; however, there are few reports
      examining its therapeutic effect on animal colitis models, and its therapeutic
      mechanisms remain unknown. The aim of this study was to elucidate the therapeutic
      effect and mechanism of Nissle1917 using murine acute and chronic colitis models.
      METHODS: Two models were used. (1) Acute model: colitis was induced by
      administration of 1.3% dextran sodium sulfate for 7 days. Nissle1917 or phosphate
      buffered saline were orally administered for 10 days. Mice were killed at day 10,
      and the colonic lesions were assessed macro- and microscopically. (2) Chronic
      model: IL-10 mice were treated with Nissle1917 or phosphate-buffered saline for 8
      weeks. After 8 weeks of treatment, mice were killed to assess the colonic lesions
      macro- and microscopically. In the acute dextran sodium sulfate colitis model,
      viable, heat-killed, or genomic DNA of Nissle1917 was orally administered for 10
      days, and the therapeutic effect was assessed. RESULTS: In the acute model,
      Nissle1917 ameliorated body weight loss, disease activity index, and macro- and
      microscopic damage. In the chronic model, it also suppressed the mucosal
      inflammatory findings and histologic damages. Moreover, heat-killed Nissle1917 or
      its genomic DNA alone also ameliorated the acute DSS colitis and viable bacteria
      macro- and microscopically. CONCLUSIONS: Nonpathogenic E. coli strain Nissle1917
      prevents both acute and chronic colitis, and its anti-inflammatory effect is
      exhibited not only by viable bacteria but also by heat-killed bacteria or its
      DNA.

PMID- 15867586
TI  - Increased transduction of human intestinal epithelial cells by adenoviral vectors
      in inflammatory bowel disease.
AB  - BACKGROUND: Delivery of genes encoding anti-inflammatory proteins has been
      proposed as a strategy for the treatment of inflammatory bowel disease (IBD). The
      goal of this study was to assess the ability of a standard adenoviral vector to
      transfect epithelial cells in intestinal explants from patients with IBD compared
      with controls. METHODS: Endoscopic colon biopsies obtained from patients with no
      history of IBD and endoscopically normal colon (n = 4), patients with a history
      of ulcerative colitis (UC; n = 5), and patients with a history of Crohn's disease
      (CD; n = 3) were placed in explant culture and exposed to an adenoviral vector
      carrying the nuclear targeted beta-galactosidase reporter gene. RESULTS: X-Gal
      staining showed that the total number of transduced cells per square millimeter
      was greater in UC explants than in controls (mean, 11.3 versus 0.9 blue
      nuclei/mm, respectively; P < 0.02) and that the frequency of epithelial cell
      transduction was greater in UC explants than in controls (86% versus 47% of
      explants, respectively; P = 0.01). Transduction of mature columnar surface
      epithelial cells occurred exclusively in UC and CD explants and was not seen in
      controls. Attenuated epithelial cells at sites of tissue damage or ulceration
      showed increased transduction compared with mature columnar epithelial cells (62%
      versus 19% of occurrences, respectively; P < 0.0001). CONCLUSIONS: We conclude
      that intestinal epithelial cells from IBD patients are more readily transfected
      by standard adenoviral vectors than are those from control patients. These
      results suggest that targeting genes to inflamed intestine through the luminal
      route may be possible.

PMID- 15867587
TI  - Biodiversity of the mucosa-associated microbiota is stable along the distal
      digestive tract in healthy individuals and patients with IBD.
AB  - BACKGROUND: The mucosa-associated microbiota, being very close to the
      inflammatory process associated with inflammatory bowel disease (IBD), may have a
      pathogenic role. We used a culture-independent method to analyze the mucosa
      associated microbiota in IBD patients at various points of the distal digestive
      tract. METHODS: Thirty-five patients (20 with Crohn's disease, 11 with ulcerative
      colitis, and 4 controls) underwent colonoscopy. Biopsies (n = 126) were taken
      from 4 sites: the ileum, right colon, left colon, and rectum. Fecal samples were
      also obtained from 7 individuals. Temporal temperature gradient gel
      electrophoresis (TTGE) of 16S rDNA was used to evaluate dominant species
      diversity. TTGE profiles were compared using software that measures the degree of
      similarity. RESULTS: In a given individual, the overall similarity percentage
      between the 4 segments of the distal digestive tract was 94.7 +/- 4.0%,
      regardless of clinical status. The average similarity of all profiles for a given
      segment was 59.3 +/- 18.3% in the overall population. Dendrogram analysis showed
      that TTGE profiles did not cluster with clinical status. Differences were
      observed between the dominant fecal microbiota and the mucosa-associated
      microbiota of all 4 sites, with similarity percentages less than 92%.
      CONCLUSIONS: These results confirm that the dominant species differ between the
      mucosa-associated and fecal microbiota. They also show that, in a given
      individual, the microbiota is relatively stable along the distal digestive tract,
      showing a slight evolution in dominant species diversity from the ileum to the
      rectum, in both healthy subjects and patients with IBD.

PMID- 15867588
TI  - Molecular characterization of rectal mucosa-associated bacterial flora in
      inflammatory bowel disease.
AB  - BACKGROUND: Colorectal bacteria may play a role in the pathogenesis of
      inflammatory bowel disease (IBD). To test the hypothesis that, in affected
      patients, the numbers of potentially protective mucosal bacteria might be reduced
      and pathogenic species increased, we compared rectal mucosa-associated flora in
      patients with IBD and normal controls. METHODS: Snap-frozen rectal biopsies taken
      at routine diagnostic colonoscopy from 33 patients with ulcerative colitis, 6
      patients with Crohn's disease, and 14 controls with normal colonoscopy were
      processed, and individual bacterial groups were counted using fluorescent in situ
      hybridization. RESULTS: Bacteria were mostly found apposed to the epithelial
      surface and within crypts. Epithelium-associated counts of bifidobacteria in
      active [median 15/mm of epithelial surface (range, 4-56), n = 14] and quiescent
      ulcerative colitis [26/mm (range, 11-140), n = 19] were lower than in controls
      [56/mm (range, 0-144), n = 14; P = 0.006 and P = 0.03, respectively]. Conversely,
      epithelium-associated Escherichia coli counts were higher in active [82/mm
      (range, 56-136)] than inactive ulcerative colitis [6/mm (range, 0-136), P =
      0.0001] or controls [0/mm (range, 0-16), P < 0.0001]. Epithelium-associated
      clostridia counts were also higher in active [3/mm (range, 0-9)] than inactive
      colitis [0/mm (range, 0-9), P = 0.03] or controls [0/mm (range, 0-1); P =
      0.0007]. Epithelium-associated E. coli counts were higher in Crohn's disease
      [42/mm (range, 3-90), n = 6] than controls (P = 0.0006). E. coli were also found
      as individual bacteria and in clusters in the lamina propria in ulcerative
      colitis and Crohn's disease but in none of the controls (P < 0.01). Numbers of
      Lactobacillus and Bacteroides showed no differences between patient groups.
      CONCLUSIONS: The reduction in mucosa-associated bifidobacteria and increase in E.
      coli and clostridia in patients with IBD supports the hypothesis that an
      imbalance between potentially beneficial and pathogenic bacteria may contribute
      to its pathogenesis.

PMID- 15867589
TI  - Impairment of health-related quality of life in patients with inflammatory bowel
      disease: a Spanish multicenter study.
AB  - BACKGROUND: Inflammatory bowel disease impairs patients' perception of health and
      has a negative impact on health-related quality of life (HRQOL). Most studies
      include patients from a single hospital. This may bias limit results through the
      use of small patient samples and/or samples within a restricted disease spectrum.
      METHODS: HRQOL was measured in patients with ulcerative colitis (UC) and Crohn's
      disease (CD) from 9 hospitals located in different geographical areas in Spain
      using 2 questionnaires: the Spanish version of the Inflammatory Bowel Disease
      Questionnaire (IBDQ) and the EuroQol. Results are expressed as medians. RESULTS:
      The study included 1156 patients (528 patients with UC and 628 with CD; median
      age, 35 yr; slight predominance of women, 617 versus 539). HRQOL worsened in
      parallel with disease severity to a similar extent in both UC (IBDQ scores of
      6.1, 4.7, and 4.0 for the 3 disease severity groups, respectively) and CD (IBDQ
      scores of 6.1, 5.0, and 4.1, respectively). A similar inverse relation between
      clinical activity and quality of life was observed when EuroQol preference values
      were used. All 5 dimensions of the IBDQ showed significantly lower scores in
      patients with active UC and CD than in patients in remission. The pattern of
      scores by IBDQ dimensions differed between patients in relapse (who scored worse
      on the digestive symptoms dimension) and patients in remission. Variables related
      with disease activity, time of evolution since diagnosis and female sex, were
      significantly associated with having a worse perception of HRQOL. The type of
      disease or geographical area of residence did not influence results on the IBDQ.
      CONCLUSIONS: UC and CD impair patients' HRQOL, and the degree of impairment
      depends on disease activity but is independent of the type of disease and place
      of residence.

PMID- 15867590
TI  - Immunogenicity of biological agents in inflammatory bowel disease.

PMID- 15867591
TI  - The time has come for NOD2/CARD15 testing for families with Crohn's disease: pro.

PMID- 15867592
TI  - NOD2, not yet: con.

PMID- 15867593
TI  - To test or "NOD-2" test: what are the questions? The balanced viewpoint.

PMID- 15867594
TI  - Preventing postoperative recurrence in Crohn's disease with 6-mercaptopurine and
      azathioprine: approaching the cutting edge.

PMID- 15867595
TI  - Progressive dysphagia caused by isolated esophageal involvement of Crohn's
      disease.

PMID- 15867596
TI  - Potential danger in the medical use of Trichuris suis for the treatment of
      inflammatory bowel disease.

PMID- 15867597
TI  - Why is fertility an issue for HIV-infected and at-risk women?

PMID- 15867599
TI  - Overview of why hormones may be an issue.

PMID- 15867600
TI  - The early work on hormonal contraceptive use and HIV acquisition.

PMID- 15867601
TI  - Hormonal upregulation of CCR5 expression on T lymphocytes as a possible mechanism
      for increased HIV-1 risk.

PMID- 15867602
TI  - Prospective clinical trials designed to assess the use of hormonal contraceptives
      and risk of HIV acquisition.

PMID- 15867603
TI  - Effect of contraceptive methods on natural history of HIV: studies from the
      Mombasa cohort.

PMID- 15867605
TI  - Issues regarding use of hormonal contraceptives in clinical trials of
      antiretroviral therapy.

PMID- 15867606
TI  - Basic pharmacological interactions and how they may impact on one another.

PMID- 15867607
TI  - Impact of pregnancy and menopause on CD4 cell counts.

PMID- 15867608
TI  - Data from the United States Food and Drug Administration.

PMID- 15867609
TI  - Data from clinical trials.

PMID- 15867610
TI  - Data from the French cohort studies and framing the French contraceptive
      guidelines.

PMID- 15867611
TI  - Review of what is being used: HIV-uninfected population national data from the
      National Survey of Family Growth.

PMID- 15867612
TI  - Review of available contraceptives.

PMID- 15867613
TI  - Overview on source of the virus, viral measurement and variability.

PMID- 15867614
TI  - Effect of the menstrual cycle on virological parameters.

PMID- 15867615
TI  - Effect of the menstrual cycle on immunological parameters in the human female
      reproductive tract.

PMID- 15867616
TI  - Effect of pregnancy.

PMID- 15867617
TI  - Effect of exogenous hormones.

PMID- 15867618
TI  - Roundtable discussion.

PMID- 15867623
TI  - Effect of estrogen receptors (reports from the FDA, NIH, ACOG, and NAMS) and the
      role of testosterone and bone density.

PMID- 15867625
TI  - Androgen deficiency and the role of testosterone administration in HIV-infected
      women.

PMID- 15867626
TI  - A review of the conference from the perspective of the HIV-infected, or at-risk
      woman, both nationally and internationally, at various points in the life cycle.

PMID- 15867627
TI  - Contraceptive use patterns in countries with different levels of HIV epidemic.

PMID- 15867629
TI  - Closing remarks: NIH research prospective.

PMID- 15867631
TI  - HIV-infected population national data.

PMID- 15867632
TI  - International data.

PMID- 15867633
TI  - Review of non-hormonal contraception (condoms, intrauterine devices, nonoxynol-9
      and combos) on HIV acquisition.

PMID- 15867634
TI  - Consortium of otolaryngology--head and neck surgery journals to collaborate in
      maintenance of high ethical standards.

PMID- 15867635
TI  - Botox, dysgeusia, and undiscovered public knowledge.

PMID- 15867636
TI  - Cytokine amplification by respiratory syncytial virus infection in human nasal
      epithelial cells.
AB  - OBJECTIVES: Respiratory syncytial virus (RSV) is an important cause of upper
      respiratory infections and is known to play a causal role in the pathogenesis of
      rhinitis, sinusitis, acute otitis media, and pneumonia. RSV appears to prime the
      respiratory tract to secondary inciting events, such as bacterial or antigen
      challenges. To study the proinflammatory priming effects of RSV infection,
      cytokine expression was measured in well-differentiated human nasal epithelial
      cells (WD-NE) after RSV infection alone or after subsequent tumor necrosis factor
      (TNF)-alpha stimulation. STUDY DESIGN: In vitro investigation. METHODS: Human
      nasal epithelial cells were obtained from surgical specimens and allowed to
      differentiate in air-liquid interface cultures until ciliation and mucus
      production were evident. Two experimental paradigms were used. First,
      accumulation of cytokines in the media was measured by real-time, quantitative
      reverse-transcriptase polymerase chain reaction (RT-PCR) and enzyme-linked
      immunosorbent assay after RSV infection alone. In the second set of experiments,
      cytokines were also measured after TNF-alpha stimulation in both RSV-infected and
      uninfected cultures. RESULTS: RSV infection of WD-NE resulted in significant
      accumulations of interleukin (IL)-6, IL-8, and RANTES when compared with findings
      in control samples. Real-time, quantitative RT-PCR demonstrated significant
      increases in IL-8 gene expression following RSV infection when compared to
      controls. Secondary TNF-alpha stimulation following well-established (i.e., 72 h)
      RSV infection induced marked increases in IL-6, IL-8, and RANTES when compared
      with both RSV infection alone and TNF-alpha stimulation alone. CONCLUSIONS: These
      findings suggest that RSV infection primes nasal epithelial cells to secondary
      proinflammatory challenge, resulting in a hyperimmune response. RSV-induced
      priming of a hyperimmune response may be important in the pathogenesis of
      sinusitis, acute otitis media, and pneumonia.

PMID- 15867637
TI  - Complications and the time to repair of mandible fractures.
AB  - OBJECTIVE: Treatment delays in the operative management of mandible fractures are
      often unavoidable. We were interested in determining whether delays increased the
      incidence of complications in these patients. STUDY DESIGN AND SETTING: A
      retrospective chart review was performed on all patients who presented to the San
      Francisco General Hospital with an operative mandible fracture in 2002. On the
      basis of the number of days from initial injury to surgery, the patients were
      divided into two groups: those repaired in 3 days or less and those repaired
      after 3 days. The incidence of infectious and technical complications was then
      compared between these groups. Substance abuse was also evaluated for its role in
      complication risk. RESULTS: Of the 84 patients in the study, 11 had infectious
      complications, and 10 had technical complications. Although treatment delay did
      not increase the risk of developing an infectious complication, substance abuse
      considerably increased this risk. The incidence of technical complications was
      remarkably higher in patients repaired after 3 days. CONCLUSION: Although
      patients with mandible fractures treated after 3 days do not have a higher risk
      of developing an infectious complication, this risk is elevated in patients who
      abuse substances regularly. The risk of technical complications increases with
      treatment delay, and therefore the surgical team must be even more vigilant when
      reducing these fractures.

PMID- 15867638
TI  - Impact of duty hour limits on resident training in otolaryngology.
AB  - HYPOTHESIS: Implementation of Accreditation Council for Graduate Medical
      Education (ACGME) duty hour standards has had limited effects on resident
      training in otolaryngology. STUDY DESIGN: Retrospective survey of residents and
      residency program directors (PDs). METHODS: Surveys were mailed to residents and
      PDs in otolaryngology asking about compliance with ACGME duty hour standards and
      perceptions of changes brought on by the new regulations. RESULTS: : Surveys were
      returned by 53.5% of PDs and 29.9% of residents. A majority of PDs described
      changes made to achieve compliance as "minor;" this consisted most commonly of
      altering call structure, although some programs hired new support staff or
      faculty. Mean estimated costs for changes were $14,211. Residents reported
      working a mean of 67.5 hours per week. Among PDs and residents, only 60% to 70%
      reported always being in compliance with the main components of the duty hour
      standards. Residents were largely divided in their opinions as to whether the
      duty hour limits had led to improvements in patient care, resident education,
      fatigue, or errors, although most felt that improvement in resident morale had
      occurred. PDs were more negative because almost half disagreed that improvement
      had occurred in any of these areas. CONCLUSIONS: Compliance with ACGME duty hour
      standards remains challenging in otolaryngology. Neither residents nor PDs agree
      that implementation of the duty hour standards has led to the intended
      improvements in patient care or resident education, although most agree that
      resident morale has improved. Further study of objective patient care and
      educational outcome measures is indicated to validate the need for this change in
      residency training.

PMID- 15867639
TI  - Robotic microlaryngeal surgery: a technical feasibility study using the daVinci
      surgical robot and an airway mannequin.
AB  - OBJECTIVES/HYPOTHESIS: The trend toward minimally invasive surgery has led to the
      development and mastery of endoscopic and laparoscopic surgical techniques. These
      minimally invasive approaches, which only two decades ago were either novel or
      experimental, are now mainstream. More recently, robot-assisted surgery has
      evolved as an adjunct to open and endoscopic techniques. Surgical robots are now
      approved by the United States Food and Drug Administration for a variety of
      thoracic and abdominal/pelvic surgical procedures. The purpose of this study is
      to demonstrate the technical feasibility of robot-assisted microlaryngeal
      surgery. STUDY DESIGN: Experimental surgical manipulation of the larynx in an
      airway mannequin with a surgical robot. METHODS: A variety of laryngoscopes and
      mouthgags, coupled with the daVinci Surgical Robot's (Intuitive Surgical,
      Sunnyvale, CA) 0-degree and 30-degree, two-dimensional and three-dimensional
      endoscopes, were utilized to optimize visualization of the larynx in an airway
      mannequin. Five millimeter and 8 mm microinstruments compatible with the daVinci
      robot were utilized to manipulate different elements of the larynx. Experiments
      were recorded with both still and video photography. RESULTS: The endoscope and
      robotic arms of the daVinci robot are well suited to airway surgery. CONCLUSIONS:
      Robot-assisted laryngeal surgery can be performed with currently available
      technology. The potential for fine manipulation of tissues, increased freedom of
      instrument movement, and endolaryngeal suturing may increase the precision of
      endoscopic laryngeal microsurgery and offers the potential to increase the
      variety of laryngeal procedures that can be performed endoscopically.

PMID- 15867640
TI  - Alcohol withdrawal prophylaxis in patients undergoing surgical treatment of head
      and neck squamous cell carcinoma.
AB  - OBJECTIVES: Alcohol abuse is common in patients with squamous cell cancer of the
      head and neck. Postoperative alcohol withdrawal is associated with increased
      morbidity and prolonged hospitalization and is commonly treated with
      benzodiazepines. We reviewed our experience with benzodiazepine prophylaxis in
      high-risk patients undergoing surgical treatment of head and neck cancer. We
      sought to determine whether benzodiazepine prophylaxis was successful in
      preventing complications from alcohol withdrawal. STUDY DESIGN: Nonrandomized,
      retrospective patient analysis. METHODS: The medical records of all patients
      diagnosed with squamous cell carcinoma of the head and neck from 1999 to 2004
      were retrospectively reviewed. Patients who underwent surgical resection and who
      were considered high risk for postoperative alcohol withdrawal received
      benzodiazepine prophylaxis following an established institutional protocol and
      comprised the study group. RESULTS: Of 96 patients who met study criteria, 13
      (13.5%) patients developed alcohol withdrawal symptoms, and 9 (9.4%) patients
      developed delirium tremens. Patients who manifested alcohol withdrawal remained
      in the hospital an average of 10.8 days longer (19.0 vs. 8.2) and had an overall
      complication rate of 50% (11 of 22) versus a 17.6% (13 of 74) complication rate
      in patients that did not develop withdrawal (P < .05). CONCLUSIONS: Alcohol
      withdrawal is associated with a significantly greater incidence of postoperative
      complications and duration of hospitalization. Benzodiazepine prophylaxis does
      not prevent postoperative alcohol withdrawal symptoms in all patients at risk.
      Alternate methods of prophylaxis should be explored.

PMID- 15867641
TI  - HIV-associated cervicodorsal lipodystrophy: etiology and management.
AB  - OBJECTIVES: To familiarize the otolaryngologist with the evaluation and
      management of cervicodorsal manifestations of lipodystrophy in patients who have
      been treated with HIV protease inhibitor medications. In addition, to share the
      benefits obtainable with ultrasonic tumescent liposuction treatment. STUDY
      DESIGN: Retrospective chart review of patients presenting to the senior author
      with symptomatic hypertrophic cervicodorsal fat pad attributable to HIV infection
      and HIV protease inhibitor use. RESULTS: Eight patients presented for evaluation
      of hypertrophic cervicodorsal fat pads between January 1, 2002 and December 31,
      2004. All patients had been on protease inhibitors in the past and had minimal
      resolution after discontinuing offending agent. Most common presenting problems
      include disfigurement, limited range of upper extremity and neck motion, neck and
      back discomfort, and difficulty with sleep including sleep-study-confirmed
      obstructive sleep apnea. Five of eight patients underwent ultrasonic tumescent
      liposuction. Three patients had satisfactory improvement of symptoms after the
      first surgery, whereas the other two required additional operative sessions. No
      complications of hematoma, seroma, infection, prolonged pain, or re-accumulation
      of fat pad were encountered. The primary obstacle in the three nonoperative
      patients was insurance denial on the basis of deemed lack of established
      necessity. CONCLUSIONS: Cervicodorsal lipodystrophy is a well-recognized outcome
      of prolonged HIV infection and side effect of certain HIV medications. Patients
      may present with both esthetic and functional issues related to the excess
      tissue. Although cessation of associated medications may halt further
      progression, this alone does resolve the symptoms. Ultrasonic tumescent
      liposuction is shown in this study to be a well-suited modality for reduction of
      this fibrous adipose tissue. Multiple sessions may be necessary to achieve
      satisfactory results because of the tenacity of the tissue. It is important for
      the otolaryngologist to be familiar with the head and neck issues relevant to
      this disorder and its treatment.

PMID- 15867642
TI  - Preservation of hearing in cochlear implant surgery: advantages of combined
      electrical and acoustical speech processing.
AB  - OBJECTIVES/HYPOTHESIS: This study documents the importance of preserving residual
      low-frequency acoustic hearing as those with more residual hearing are selected
      for cochlear implantation. Surgical strategies used for hearing preservation with
      a short hybrid cochlear implant are outlined. The benefits of preserved residual
      low-frequency hearing, improved word understanding in noise, and music
      appreciation are described. STUDY DESIGN: Multicenter, prospective, single
      subject design. METHODS: Records were reviewed of 21 individuals participating in
      an Food and Drug Administration (FDA) feasibility clinical trial who have
      received an Iowa/Nucleus 10 mm electrode. A second group of subjects receiving
      implants at the University of Iowa that have used the 10 mm device between 2
      years and 6 months were also reviewed. Outcome measures included standardized
      tests of monosyllabic word understanding, spondees in noise, and common melody
      recognition. RESULTS: Low-frequency hearing was maintained in all individuals
      immediately postoperative. One subject lost hearing at 2.5 months postoperative
      after a viral infection. The group has averaged a loss of -9 dB low-frequency
      acoustic hearing between 125 and 1,000 Hz. Monosyllabic word understanding scores
      at 6 months for a group being followed for an FDA clinical trial using the
      implant plus hearing aids was 69% correct. For the long-term group receiving
      implants at Iowa, monosyllabic word understanding in those who have used the
      device between 6 months and 2 years is 79%. Other important findings include
      improved recognition of speech in noise (9 dB improvement) as compared with
      standard cochlear implant recipients who were matched for speech recognition in
      quiet and near normal recognition of common melodies. CONCLUSION: The surgical
      strategies outlined have been successful in preservation of low-frequency hearing
      in 96% of individuals. Combined electrical and acoustical speech processing has
      enabled this group of volunteers to gain improved word understanding as compared
      with their preoperative hearing with bilateral hearing aids and a group of
      individuals receiving a standard cochlear implant with similar experience with
      their device. The improvement of speech in noise and melody recognition is
      attributed to the ability to distinguish fine pitch differences as the result of
      preserved residual low-frequency acoustic hearing. Preservation of low-frequency
      acoustic hearing is important for improving speech in noise and music
      appreciation for the hearing impaired, both of which are important in real-life
      situations.

PMID- 15867643
TI  - A blinded, randomized, controlled study on the effect of buffered 0.9% and 3%
      sodium chloride intranasal sprays on ciliary beat frequency.
AB  - BACKGROUND: There are conflicting reports regarding the effect of intranasal
      saline sprays on the various components of the mucociliary clearance system. This
      study evaluates the effect of normal saline and hypertonic saline on the ciliary
      beat frequency (CBF). METHODS: Eight healthy volunteers were randomized to
      receive 0.9% saline spray to one nostril and 3.0% saline spray to the other.
      Ciliated cells were collected, and the CBF was calculated using computerized
      microphotometry. RESULTS: Although neither solution significantly altered the CBF
      from baseline measurements, there was a significant difference between the CBFs
      of the two solutions at 5 minutes postadministration (9.1 Hz with 0.9% saline,
      10.1 Hz with 3.0% saline, P < .05). This was a transient effect and was not seen
      when cells were examined at 60 minutes postadministration. CONCLUSION: The
      administration of hypertonic saline results in a significantly faster CBF 5
      minutes after administration. This effect is not seen 60 minutes after
      administration.

PMID- 15867644
TI  - Prospective phase II trial of concomitant boost radiotherapy for stage II
      nasopharyngeal carcinoma: an evaluation of response and toxicity.
AB  - INTRODUCTION: Stage II nasopharyngeal carcinoma (NPC) treated with conventionally
      fractionated radiotherapy results in loco-regional control of around 80%. This
      report aims to document the outcome of Stage II NPC patients treated with
      external beam radiotherapy delivered using an accelerated concomitant boost (C
      Boost) schedule. METHODS AND MATERIALS: Twenty-five 1997 AJCC Stage II NPC
      patients were enrolled and analyzed in this preliminary report. The primary tumor
      and clinically involved nodes received a total dose of 72 Gy in 42 fractions. C
      Boost for gross disease consisted of 18 Gy in 12 fractions commencing on day 19
      and was delivered at least 6 hours after the first dose. Patients were assessed
      for response, survival, and toxicity. RESULTS: With a median follow-up of 24
      months, only one patient had pathologically confirmed local recurrence,
      necessitating IMRT. Two developed distant metastases for which they received
      chemotherapy. One died from systemic disease after refusing treatment for
      persistent neck lymphadenopathy. Two-year loco-regional control rates, overall
      survival and disease-free survival rates were 96%, 96%, and 88%, respectively.
      All patients experienced some degree of acute and/or late toxicity. However, the
      toxicity profile was comparable to that seen following standard fractionation.
      Acute or late toxicities directly attributable to C-Boost were not observed.
      CONCLUSION: This C-Boost radiotherapy regimen administers a substantially higher
      biologically effective dose compared with conventional radiation schedules.
      Preliminary locoregional control and survival rates are promising with no
      significant acute and/or late toxicities.

PMID- 15867645
TI  - Quantification of angiogenesis in otosclerosis.
AB  - OBJECTIVES/HYPOTHESIS: The determinants of clinical versus histologic
      otosclerosis are unknown, but angiogenesis is associated with active disease. We
      hypothesized that quantification of angiogenesis in otosclerotic human temporal
      bones could reveal significant differences between clinical and histologic cases.
      STUDY DESIGN: We reviewed all otosclerosis specimens meeting criteria from the
      temporal bone collection of the Massachusetts Eye and Ear Infirmary and 10 normal
      controls. METHODS: Digital images were taken at predilection sites, followed by
      computer-assisted analysis. Canalicular area (CA), the aggregate of vascular
      spaces within bone, microvessel density (MVD), area, and depth were the main
      measures. Evidence of a direct connection between local vessels and the
      vasculature of the otosclerotic focus was also recorded for each specimen.
      RESULTS: The average area (mm) and depth (number of sections containing
      otosclerosis) of clinical lesions was significantly greater than histologic
      lesions. Total microvessel counts were significantly greater in clinical versus
      histologic lesions, and both clinical and histologic lesions contained
      significantly greater numbers of microvessels than the normal otic capsule. CA
      was also significantly higher in clinical lesions. MVD was slightly but not
      significantly higher in clinical lesions. Importantly, a direct connection
      between named vessels and the otosclerotic vasculature was significantly more
      frequent in clinical lesions. CONCLUSIONS: Computer-assisted quantification
      revealed significantly greater measures of angiogenesis in clinical versus
      histologic otosclerosis. Direct connection to adjacent vessels may support
      angiogenesis in this disease. Sustained angiogenesis may be an important
      determinant of clinical otosclerosis.

PMID- 15867646
TI  - Conjunctival melanoma: the role of conservative surgery and radiotherapy in
      regional metastatic disease.
AB  - OBJECTIVE: To evaluate prognostic factors and determine the role of conservative
      surgery and radiotherapy in managing metastatic conjunctival malignant melanoma
      (MM) involving preauricular/submandibular lymph nodes. METHOD: A retrospective
      analysis (1990-2003) of clinical and histopathologic data from 12 patients
      presenting with regional metastases after failed local treatment for conjunctival
      MM. Patients received a common, multispecialty, conservative management approach:
      wide local excision, topical cryotherapy or radiotherapy to conjunctival MM
      (orbital exenteration for more advanced local disease), lumpectomy, and adjuvant
      "ring" radiotherapy of regional metastases, with chemotherapy for distant
      metastases. RESULTS: Median age at primary diagnosis was 51 (range 28-86) years
      with equal sex predilection. Six of the 12 patients had primary tumors of the
      bulbar conjunctiva; the remainder arose in the palpebral conjunctiva, the
      caruncle, or the fornix. Of 11 originating in primary acquired melanosis (PAM), 2
      were amelanotic. Epithelioid tumor cells were noted histologically in seven of
      eight specimens in which cell type could be determined. Eight tumors metastasised
      to preauricular nodes, three to submandibular and one to both, with a median
      interval of 23 (range 12-108) months after primary diagnosis. After conservative
      surgery and "ring irradiation," 7 of 12 patients remained free of regional nodal
      relapse at median interval of 16 (range 3-126) months. Five patients developed
      regional nodal recurrence at median interval of 11 (range 6-13) months, 3 of whom
      were within radiotherapy portals. Eight patients developed distant metastasis at
      median interval of 44 (range 22-138) months. Eleven patients had tumor-related
      death. The mean Kaplan-Meier adjusted survival time after primary diagnosis was
      76 months with death ensuing postregional metastasis within a median 18 (range 4
      127) months. The sole survivor's follow-up duration was 56 months. CONCLUSION:
      Locoregional metastasis after treatment for conjunctival MM is associated with a
      poor prognosis. Both epithelioid tumor cells and PAM are associated with
      disseminating disease and poorer outcome. Literature review has failed to
      demonstrate advantages of mutilating radical surgery over a conservative approach
      in this rare disease.

PMID- 15867647
TI  - Microbiology of acute and chronic maxillary sinusitis associated with an
      odontogenic origin.
AB  - OBJECTIVES: : To study the microbiology of sinusitis associated with odontogenic
      origin. METHODS: : Aspirates of 20 acutely and 28 chronically infected maxillary
      sinuses that were associated with odontogenic infection were processed for
      aerobic and anaerobic bacteria. RESULTS: : A total of 66 isolates were recovered
      from the 20 cases of acute sinusitis (3.3/specimen), 16 aerobic and facultatives,
      and 50 anaerobic. Aerobes alone were recovered in 2 (10%) specimens, anaerobes
      only in 10 (50%), and mixed aerobic and anaerobic bacteria in 8 (40%). The
      predominant aerobic were alpha-hemolytic streptococci (5), microaerophilic
      streptococci (4), and Staphylococcus aureus (2). The predominant anaerobes were
      anaerobic Gram-negative bacilli (22), Peptostreptococcus (12), and Fusobacterium
      spp. (9). A total of 98 isolates were recovered from the 28 cases of chronic
      sinusitis (3.5/patient): 21 aerobic and facultatives and 77 anaerobic. Aerobes
      were recovered in 3 (11%) instances, anaerobes only in 11 (39%), and mixed
      aerobic and anaerobic bacteria in 14 (50%). The predominant aerobes were alpha
      hemolytic streptococci (7), microaerophilic streptococci (4), and S. aureus (5).
      The predominant anaerobes were Gram-negative bacilli (41), Peptostreptococcus
      (16), and Fusobacterium spp. (12). Thirteen beta-lactamase-producing bacteria
      (BLPB) were recovered from 10 (50%) patients with acute sinusitis and 25 BLPB
      from 21 (75%) patients with chronic sinusitis. No correlation was found between
      the predisposing odontogenic conditions and the microbiological findings.
      CONCLUSIONS: : These data illustrate the similar microbiology of acute and
      chronic maxillary sinusitis associated with odontogenic infection where anaerobic
      bacteria predominate in both types of infections.

PMID- 15867648
TI  - Informed consent in sinus surgery: link between demographics and patient desires.
AB  - OBJECTIVE: To evaluate and understand differences in expectations according to
      patient demographics during the informed consent process for functional
      endoscopic sinus surgery (FESS). STUDY DESIGN: Multi-institutional, cross
      sectional survey design. METHODS: Anonymous surveys were administered to patients
      in two tertiary academic centers with a chief complaints relating to "allergy and
      sinus" problems. Patients completed and eight-item questionnaire that assessed
      demographics and the nature and level of risks that patients wished to be
      informed of before FESS. Univariate and multivariate analyses were performed to
      assess for differences in patient desires related to FESS risks according to
      demographics. RESULTS: Three hundred eighty-nine completed surveys were analyzed.
      Younger patients (P = .049), white patients (P = .0026), and more educated
      patients (P = .0033) wished to know about complications at the lowest risks
      levels (lowest incidence), regardless of severity. With regards to specific
      complications, black patients and patients with less formal education were less
      interested in being informed about the potential risks of orbital complications,
      cerebrospinal fluid leak, or possible need for revision surgery. Multivariate
      analysis confirmed that race, education, age were independently significant
      factors in determining response. CONCLUSION: Demographic-related differences
      exist in patient's desires and expectations in the informed consent process for a
      sinus procedure. Physicians should be aware of these differences when counseling
      patients about sinus surgery. More research is needed to elucidate the factors
      that underlie the observed differences.

PMID- 15867649
TI  - Association of serotonin transporter gene polymorphism with obstructive sleep
      apnea syndrome.
AB  - BACKGROUND AND OBJECTIVE: Obstructive sleep apnea syndrome (OSAS) is a common
      condition characterized by repetitive pharyngeal collapse during sleep and
      daytime sleepiness. There is genetic predisposition to sleep disorders. Serotonin
      is involved in the regulation of sleep. The synaptic 5-hydroxytryptamine (HT) is
      inactivated by presynaptic reuptake, which is mediated by the serotonin
      transporter. Blockage of the serotonin transporter leads to increased
      extracellular 5-HT. Polymorphism of the serotonin transporter gene (STG) leads to
      alterations in serotonin level and may be important in OSAS. In this study, we
      aimed to assess the role of STG polymorphism in OSAS. METHODS: Twenty-seven OSAS
      patients and 162 healthy volunteers were involved in the study. STG polymorphism
      was investigated using leukocytes obtained from peripheral blood. RESULTS: There
      was no difference between the genotypes and allele frequencies of the patients
      and controls regarding VNTR and HTTLPR polymorphisms (P > .05). The VNTR and
      HTTLPR variants and the frequencies of 12/12, 12/10, L, and S alleles were not
      significantly different between male and female control subjects (P > .05). The
      12/12 and SS genotypes were over-represented in the female patients, whereas
      12/10 and LL genotypes were over-represented in the male patients (P < .05). The
      genotypes 12 to 12 were over-represented in the male controls, whereas the
      genotypes 12 to 10 and L/S were over-represented in the male patients (P < .05).
      The alleles 10 and L were more frequent in the male patients than male controls
      (P < .05). The genotypes of female patients and female controls were not
      significantly different (P > .05). The allele 10 and L were less frequent in the
      female patients than female controls with Fisher's exact testing (P < .05). There
      was no relation between genotypes and clinical data of the patients (P > .05).
      CONCLUSION: STG polymorphism appears to be associated with the occurrence of
      OSAS, especially in male patients. Absence of association of between genetic
      variants and polysomnography findings may suggest that some mechanisms other than
      STG polymorphism are involved in OSAS pathophysiology. Our results need
      confirmation in a larger group of patients with OSAS.

PMID- 15867650
TI  - Acoustic rhinometry and paranasal sinuses: a systematic study in models, anatomic
      specimens, and in vivo.
AB  - OBJECTIVE/HYPOTHESIS: Acoustic rhinometry (AR) evaluates the cross-sectional
      areas (CSA) of the nasal cavity through acoustic reflections. The aim of this
      study was to test whether the paranasal sinuses are a cause for the measurement
      of increased CSA in the posterior cavum of the nose. STUDY DESIGN: : Experimental
      study to evaluate the influence of paranasal sinus volume on AR measurements in
      two anatomic nose models, an anatomic specimen, and seven individuals. METHODS:
      The paranasal sinus volume was systematically reduced by filling of the maxillary
      sinus with saline. The paranasal sinus ostia were enlarged in the models and the
      anatomic specimen by infundibulotomy and supraturbinal fenestration, with AR
      repeated thereafter. RESULTS: No modification of the posterior area-distance
      curve was found in the models, the specimen, and the individuals after changing
      the volume of the maxillary sinus with unmodified anatomy of the paranasal sinus
      ostia. The apparent CSA measured in the posterior cavum after infundibulotomy and
      supraturbinate fenestration in the models and the specimen increased with the
      volume of the paranasal sinuses. CONCLUSION: Regular anatomy provided, AR reveals
      reproducible measurements that correspond with the actual CSA up to the ostia of
      the paranasal sinuses. Untypical large openings to the paranasal sinuses (e.g.,
      after paranasal sinus surgery) appear to contribute to the inaccuracy of AR by
      overlapping paranasal sinus CSA with the posterior part of the area distance
      curve.

PMID- 15867651
TI  - Incidental finding of dysgeusia relieved by injections of botulinum toxin A.
AB  - OBJECTIVE: We report the unique finding of hemifacial spasm and associated
      dysgeusia that resolved after treatment with botulinum toxin A (BTX-A). STUDY
      DESIGN: Case report. METHODS: Three years after undergoing resection of an
      acoustic neuroma and subsequent resolution of postoperative left-sided facial
      nerve palsy, a 38-year-old woman presented with new onset of facial spasm and
      dysgeusia. RESULTS: After three courses of BTX-A injections during a 2-year
      period, symptoms of both facial spasm and dysgeusia resolved after treatments and
      returned between treatments. CONCLUSIONS: These findings, which have not been
      reported previously in the literature, indicate a potential role for BTX-A in the
      treatment of surgically associated dysgeusia.

PMID- 15867652
TI  - Validity of a new health-related quality of life instrument for patients with
      chronic sinusitis.
AB  - OBJECTIVE/HYPOTHESIS: To assess the validity and responsiveness of a new health
      related quality of life (HRQL) instrument for patients with chronic sinusitis.
      STUDY DESIGN: Prospective case series. METHODS: Patients with chronic sinusitis
      undergoing endoscopic sinus surgery were assessed in two otolaryngology practices
      affiliated with an academic hospital. Patient-reported HRQL was assessed using a
      new instrument (includes symptom frequency, bothersomeness, and impact scales),
      the Chronic Sinusitis Survey (CSS), and the generic SF-12 at baseline and 3
      months postsurgery. The psychometric properties of the new instrument were
      assessed including reliability, validity, responsiveness, and interpretability.
      RESULTS: Among 50 enrolled patients, 49 underwent surgery and 39 (80%) completed
      3-month follow-up. Internal consistency was high for the symptom impact scale.
      The symptom frequency and, especially, bothersomeness scales had lower internal
      consistency and were comparable with the CSS. Correlation analyses support the
      construct validity of the new measure compared with the CSS and SF-12. The
      responsiveness of the new instrument was excellent and similar to or better than
      the CSS. The mean score change was linearly related to the patient's global self
      assessment, although the CSS symptom and total score better discriminated
      patients with major or moderate degrees of improvement. CONCLUSIONS: This study
      demonstrates the validity and responsiveness of a new rhinosinusitis-specific
      HRQL instrument, the Rhinosinusitis Quality of Life survey, in patients with
      chronic sinusitis. The instrument's symptom frequency, bothersomeness, and impact
      scales compare favorably with a previously validated disease-specific and a
      generic HRQL measure. If validated in other patient populations, this disease
      specific instrument may be useful in assessing severity and outcomes of treatment
      for sinusitis.

PMID- 15867653
TI  - Clinical factors that influence the prognosis of facial nerve paralysis and the
      magnitudes of influence.
AB  - OBJECTIVE: To show the significance of various factors when predicting the
      outcome of facial nerve paralysis. DESIGN: Retrospective chart review. SETTING:
      Nihon University Itabashi Hospital in Tokyo. SUBJECTS: Four hundred sixty-seven
      patients with facial paralysis who visited the hospital within 14 days of disease
      onset. METHODS: The failure rate of complete recovery was studied for each of
      these nine factors: sex, age, varicella-zoster virus (VZV) infection as the cause
      of paralysis, initial severity of paralysis, number of days from onset of
      paralysis to the beginning of medical treatment, nerve excitability test (NET),
      stapedial reflex, lacrimal secretion, and severity of facial paralysis 1 month
      after onset. These factors were analyzed by logistic regression. RESULTS:
      Logistic regression clarified that age, VZV infection, NET response, loss of
      stapedial reflex, and the state of paralysis 1 month after the onset had
      statistical significance for the prognosis of facial paralysis. The poor recovery
      rate was greater than 50% in the patients who exhibited abnormal responses on NET
      or failed to attain recovery to grade III or better during the 1-month period
      after the onset of paralysis. These findings were therefore considered as high
      risk factors for the prognosis. The poor recovery rate was between 25% and 50% in
      patients who were 50 years or older or whose initial grading of paralysis was V
      or worse. These findings were classified as moderate risk factors. Patients with
      VZV-caused paralysis and loss of stapedial reflex had poor recovery rates of
      below 25%, and these were classified as low risk factors. CONCLUSION: It is
      possible to predict the prognosis of facial paralysis on the basis of several
      clinical findings. NET response, severe initial paralysis, age 50 years or older,
      and, as a second-stage factor, severity of facial paralysis 1 month after the
      onset were found to be especially important factors for predicting the prognosis
      of facial paralysis.

PMID- 15867654
TI  - Kaposi's sarcoma of an intraparotid lymph node leading to a diagnosis of HIV.
AB  - OBJECTIVE: Kaposi's sarcoma is a common malignancy in patients infected with HIV
      but is rarely seen in the major salivary glands. If a patient is known to be HIV
      positive, however, Kaposi's sarcoma must be considered in the differential
      diagnosis of salivary gland masses in addition to the benign and malignant
      neoplasms that occur in immunocompetent patients. We present a unique case in
      which an otherwise healthy patient was diagnosed with HIV after resection of his
      enlarged parotid gland revealed Kaposi's sarcoma. STUDY DESIGN: Case report.
      METHODS: A 58-year-old man presented with slowly enlarging bilateral parotid
      masses of approximately 3 years' duration. The patient's presentation, workup,
      and final diagnosis of Kaposi's sarcoma are discussed. RESULTS: A magnetic
      resonance imaging scan of the neck showed two right parotid lesions and one left
      parotid mass. The patient underwent a right superficial parotidectomy for a
      suspected diagnosis of Warthin's tumor, given the bilaterality of the lesions.
      Histologic evaluation of the surgical specimen revealed spindle-shaped cells with
      extravasated erythrocytes typical of Kaposi's sarcoma. After discussion of the
      results with the patient, HIV risk factors were elucidated, and subsequent
      testing revealed the patient to be HIV-positive. CONCLUSIONS: Although Kaposi's
      sarcoma is common in AIDS patients, there are few case reports of this malignancy
      arising in the salivary glands. Previously reported cases include salivary gland
      Kaposi's sarcoma in known HIV-positive patients and a handful of reports in
      patients without confirmed immunocompromise. The patient presented here is unique
      because the diagnosis of parotid gland Kaposi's sarcoma led to a new diagnosis of
      HIV. This interesting case reiterates the need for complete history taking and
      the inclusion of Kaposi's sarcoma in the differential diagnosis of salivary gland
      masses in the appropriate patient population.

PMID- 15867656
TI  - Surgery and adjuvant radiotherapy in patients with cutaneous head and neck
      squamous cell carcinoma metastatic to lymph nodes: combined treatment should be
      considered best practice.
AB  - OBJECTIVE: Patients with cutaneous squamous cell carcinoma (SCC) may develop
      metastatic SCC to nodes in the head and neck. Recent data support best outcome
      with the addition of adjuvant radiotherapy. This study aims to present further
      supportive evidence. STUDY DESIGN: Retrospective chart review. METHODS: Patients
      were identified with metastatic cutaneous SCC to nodes of the head and neck
      treated with surgery or surgery and adjuvant radiotherapy. Relapse and outcome
      were analyzed using Cox regression analysis. Disease-free survival and overall
      survival rates were calculated using Kaplan-Meier survival curves. RESULTS:
      Between 1980 to 2000, 167 patients were treated with curative intent at Westmead
      Hospital, Sydney. Median age was 67 years (range, 34-95) in 143 men and 24 women
      with a minimum follow-up of 24 months. Patients underwent surgery (21/167; 13%),
      or surgery and adjuvant radiotherapy (146/167; 87%). The majority (98/167; 59%)
      of metastatic nodes were located in the parotid and/or cervical nodes. The
      remaining 69 (41%) had metastatic cervical nodes (levels I-V). Forty-seven
      patients (28%) had recurrences, with the majority (35/47; 74%) as locoregional
      failures. On multivariate analysis, spread to multiple nodes and single-modality
      treatment significantly predicted worse survival. Patients undergoing combined
      treatment had a lower rate of locoregional recurrence (20% vs. 43%) and a
      significantly better 5-year disease-free survival rate (73% vs. 54%; P = .004)
      compared to surgery alone. CONCLUSIONS: In patients with metastatic cutaneous
      head and neck SCC, surgery and adjuvant radiotherapy provide the best chance of
      achieving locoregional control and should be considered best practice.

PMID- 15867655
TI  - Total pharyngolaryngectomy for squamous cell carcinoma of the hypopharynx: a
      review.
AB  - OBJECTIVES: To evaluate our experience with total pharyngolaryngectomy in the
      treatment of hypopharyngeal squamous cell carcinoma. STUDY DESIGN: Retrospective
      analysis of consecutively treated patients in an academic otolaryngology, head
      and neck department. METHODS: One hundred eighty patients who had total
      pharyngolaryngectomy performed for hypopharyngeal carcinoma were included in this
      study. Patients with a history of previous head and neck cancer were excluded.
      Clinicopathologic parameters were recorded and survival calculated using the
      Kaplan-Meier method. RESULTS: One hundred sixty-two (90%) of the patients were
      male, and the patients had a mean age of 62 years. The majority (91%) of patients
      had advanced overall clinical stage disease (stage 3,4). Thirty-one (17.8%) and
      43 (24%) patients developed locoregional and metastatic disease recurrence,
      respectively. The 2- and 5-year disease-specific survival rates were 72% and 52%,
      respectively. Advanced nodal stage, perineural invasion, lymphovascular invasion,
      and positive margins were predictors of poor survival on univariate analysis, and
      lymphovascular invasion was an independent prognostic factor on multivariate
      analysis. CONCLUSION: Surgery and postoperative radiotherapy remains the
      treatment against which other modalities should be compared for advanced stage
      hypopharyngeal squamous cell carcinoma.

PMID- 15867657
TI  - Giant fibrovascular polyp of the hypopharynx.

PMID- 15867658
TI  - Antiphospholipid inner ear syndrome.
AB  - OBJECTIVE: This study was initiated to clarify the possible association between
      antiphospholipid antibodies, mediators of microthrombus formation, and
      sensorineural hearing loss (SNHL) of unknown origin in a large cohort of
      patients. STUDY DESIGN: Prospective study. METHODS: The study cohort consists of
      168 adult patients (>/=18 yr) referred to the University of Pennsylvania's
      Division of Neurotology and Balance Center for diagnosis and treatment of
      progressive hearing loss with or without vertigo. A comprehensive screening panel
      of blood tests for autoimmune and infectious diseases was applied to all
      patients, including testing for anticardiolipin antibodies, anti-B2 glycoprotein,
      and lupus anticoagulant. RESULTS: Forty-two patients (25%) had at least one
      elevated antiphospholipid antibody marker. Twenty patients had two or more
      positive test results. Of the 42 patients, 64% (n = 27) met the diagnostic
      criteria for Meniere disease, and the remainder were diagnosed with idiopathic
      SNHL. Within this group of patients, 24 patients (57%) had unilateral hearing
      loss, and 18 (44%) had bilateral hearing loss. CONCLUSIONS: These data support
      the hypothesis that antiphospholipid antibodies are involved in the pathogenesis
      of some forms of inner ear dysfunction, presumably by causing microthrombus
      formation in the labyrinthine vasculature. Basic science studies are required to
      better understand the mechanisms by which antiphospholipid antibodies mediate
      inner ear dysfunction. Clinical studies to evaluate the efficacy of
      anticoagulation in this group of patients are also required.

PMID- 15867659
TI  - Measurement of upper eyelid implants curvature by ultrasound.
AB  - INTRODUCTION: The implantation of eyelid weights in the upper eyelid for
      treatment of the lagophthalmos in cases of facial paralysis was described for the
      first time in 1958 by Illig (lid loading). Whereas in the past, only rigid
      implants made of gold were used, flexible chains made of platinum are now being
      used frequently to optimize adaptation to the tarsal plate of the upper eyelid.
      The first step toward assessing the flexibility of the upper eyelid was to
      determine sonographically the various tarsal diameters of the upper eyelid in
      healthy eye subjects when the line of vision is changed. In a second step,
      patients who had received eyelid implants were examined sonographically both pre-
      and postoperatively to evaluate the curvature response of the upper eyelid after
      implantation. MATERIALS AND METHODS: The diameter of the upper eyelid tarsal
      plate in 50 healthy eye subjects was sonographically determined using a 7.5 MHz
      scanner in a noncontact mode with subjects looking straight ahead and in the
      abduction position. Rigid gold implants were implanted in 23 patients, and
      flexible platinum chains were implanted in 24 patients to treat lagophthalmos in
      facial palsy. The implant diameter was also determined by ultrasound using a 7.5
      MHz scanner in a noncontact mode with subjects looking straight ahead and in the
      abduction position. In addition, the respective upper eyelid tarsal diameters of
      the patients were sonographically determined preoperatively with subjects looking
      straight ahead and in the abduction position. RESULTS: The diameter of the upper
      eyelid tarsal plate in healthy eye subjects changes to a degree that is
      statistically significant (P < .001) when the line of vision is changed. The mean
      value of the diameter of the upper eyelid tarsal plate when looking straight
      ahead is 19.3 +/- 3.8 mm and in abduction position 30.1 +/- 6.3 mm. In the case
      of the rigid gold implants, the implant radius does not change postoperatively
      relative to the line of vision, in accordance with expectations. In contrast, in
      the case of the platinum chains, a statistically significant change (P < .001) in
      the implant diameter was found when the line of vision is changed, for a median
      postoperative follow-up period of 8 months. CONCLUSION: Changes in the upper
      eyelid tarsal plate diameter, which are dependent on the line of vision, and
      changes in the implant diameter after lid loading can be precisely represented
      using a 7.5 MHz scanner in the noncontact mode. The flexibility of the upper
      eyelid when the line of vision is changed also remains intact over an 8 month
      follow-up when using platinum chains as implant material and thus potentially
      serves to reduce postoperative complications as well.

PMID- 15867660
TI  - Measurement of absolute dimensions in endoscopic sinus surgery.
AB  - OBJECTIVE: To develop and evaluate a simple, noninvasive technique for the
      precise measurement of antrostomy dimensions using standard endoscopic views.
      METHODS: We produced an antrostomy probe and devised a method, on the basis of
      techniques of aerial planimetry, for measuring antrostomies using standardized
      endoscopic views. Ten shapes of known surface areas were measured independently
      by three experienced endoscopic sinus surgeons using 30 and 70 degree endoscopes.
      The accuracies of surgeon assessment and interobserver concordance were
      calculated. RESULTS: The three surgeons were able to calculate the surface areas
      with great precision (Pearson's coefficient of correlation > 0.85 in all cases)
      using both 30 and 70 degree endoscopes. An intraclass correlation coefficient of
      0.92 was obtained, indicating a high degree of concordance between the
      measurements obtained by different surgeons. CONCLUSION: This technique shows
      considerable promise as a tool for precise measurement of antrostomy dimensions
      in both clinical and research settings.

PMID- 15867661
TI  - Prognostic importance of paratracheal lymph node metastases.
AB  - OBJECTIVES: The aim of this retrospective study was to evaluate the prognostic
      significance of paratracheal lymph node (PTLN) metastases for tumor recurrence
      and survival for patients treated with total laryngectomy (TL) and PTLN
      dissection. STUDY DESIGN: Records from 85 patients who underwent TL combined with
      PTLN dissection for laryngeal or hypopharyngeal carcinomas were reviewed.
      RESULTS: In 20 of 85 (24%) patients, PTLN metastases were found, and in 7
      patients, extranodal spread (ENS) was present in these metastases. The incidence
      of PTLN metastases was high in patients with hypopharyngeal or cervical
      esophageal (35%) and laryngeal carcinoma with subglottic extension (27%).
      Multivariate analysis shows that the most important prognostic factor for overall
      survival is the presence of PTLN metastases with ENS (P < .0005). CONCLUSIONS:
      Because PTLN metastases with ENS is an important prognostic factor and can only
      be assessed by histopathologic examination, PTLN dissection in patients with a
      laryngeal or hypopharyngeal tumor is important for prognostication.

PMID- 15867662
TI  - Prospective, randomized, controlled clinical trial of a novel matrix hemostatic
      sealant in patients with acute anterior epistaxis.
AB  - OBJECTIVES: Floseal, a novel hemostatic sealant composed of collagen-derived
      particles and topical bovine-derived thrombin, is applied as a high-viscosity gel
      for hemostasis. This study is a prospective, randomized, controlled clinical
      trial of Floseal compared with nasal packing in patients with acute anterior
      epistaxis. STUDY DESIGN: Institutional review board-approved, prospective,
      randomized, controlled, nonblinded, crossover clinical trial. METHODS: Seventy
      consecutive patients presenting with acute anterior epistaxis were randomized to
      receive Floseal or nasal packing for control. Patients were crossed over to the
      other technique after two unsuccessful attempts of the first technique. Patients
      were seen in the clinic within 7 days for follow-up. Ten-point visual analogue
      scales were used to rank effectiveness (1 = ineffective, 10 = effective),
      physician technical ease (1 = difficult, 10 = easy), physician satisfaction (1 =
      unsatisfied, 10 = satisfied), patient discomfort during hemostasis (0 = none, 9 =
      unbearable), patient discomfort at follow-up office visit, and patient
      satisfaction. Additional data included need for subspecialist consultation to
      control bleeding, rebleeding rates within 7 days, and rebleeding at follow-up
      visit. RESULTS: Floseal (n = 35) was judged by physicians to be more effective
      than nasal packing (n = 35) at initial control of anterior epistaxis (9.9 vs.
      7.7, P < .001). Physicians found Floseal to be easier to use (9.4 vs. 3.2, P <
      .001) and were more satisfied with Floseal (9.6 vs. 3.5, P < .001). Patients
      experienced less discomfort with Floseal than with nasal packing both at initial
      control (1.4 vs. 8.9, P < .001) and at follow-up visit (0.0 vs. 8.5, P < .001),
      and Floseal patients were more satisfied overall (9.1 vs. 2.9, P < .001). Fewer
      in-person otolaryngology consultations were requested for Floseal patients (8.6%
      vs. 31.0%, P < .05). Floseal patients experienced fewer rebleeding rates within 7
      days (14% vs. 40%, P < .05). Rebleeding rates at follow-up visit were higher in
      the nasal packing than the Floseal group at time of packing removal (63% vs. 0%,
      P < .001). Eight (23%) patients were crossed over from the nasal packing group to
      the Floseal group when nasal packing was ineffective. One Floseal patient (3%, P
      < .05) was crossed over into the nasal packing group. There were no complications
      in either group. CONCLUSIONS: Floseal hemostatic sealant is a better tolerated,
      more effective, safe, and easy alternative to nasal packing in patients
      presenting with acute anterior epistaxis. Future studies may wish to evaluate
      Floseal's use in posterior epistaxis.

PMID- 15867663
TI  - A novel intranasal stent for functional rhinoplasty and nostril stenosis.
AB  - OBJECTIVES/HYPOTHESIS: The surgical correction of nostril stenosis and external
      nasal valve collapse typically involves the addition of tissue to widen and
      strengthen these areas. However, over the ensuing months, postoperative scar
      contracture may act to reverse the surgical modifications. This study aimed to
      determine the safety and efficacy of the use of nasal stents fashioned from a
      nasopharyngeal airway tube to prevent postoperative contracture at these sites.
      STUDY DESIGN: Retrospective review of six patients who underwent functional
      rhinoplasty with alar batten graft placement for nasal valve collapse and one
      patient who underwent composite graft repair of unilateral nostril stenosis.
      METHODS: Patients completed a survey inquiring about the ease of use, discomfort,
      presence of infection, and ability to breathe with these nasal stents. Patients
      also completed the NOSE (nasal obstruction symptom evaluation) instrument to
      compare their overall level of preoperative and postoperative nasal breathing.
      The functional rhinoplasty patients were examined for degree of dynamic airway
      nasal wall collapse and position of the lateral nasal wall on intranasal
      examination. RESULTS: Six of seven patients overall reported no to minimal
      discomfort, easy application, and no to minimal obstruction of nasal breathing
      with the use of the stents. One patient reported difficulty with application.
      Preoperative NOSE scores averaged 67.1 (SD 10.4), 18.6 (SD 14.6) at the time of
      splint removal, and 21.4 (SD 15.2) at 3 months after stent removal. Paired t test
      analysis showed significant differences between the NOSE scores preoperatively as
      compared with the time of splint removal (P = .0002) or 3 months after splint
      removal (P = .0003). All patients demonstrated a significant reduction of lateral
      nasal wall collapse with inspiration on physical examination. CONCLUSIONS: The
      use of nasal stents made from nasopharyngeal airway tubes is a safe, convenient,
      and economic treatment for the prevention of contracture after surgical
      correction of nostril stenosis or nasal valve insufficiency.

PMID- 15867664
TI  - Cochlear implant fixation using titanium screws.

PMID- 15867665
TI  - Novel techniques to guide the neodymium-doped yttrium aluminum garnet laser fiber
      for laser surgery of upper aerodigestive tract squamous cell carcinoma.

PMID- 15867666
TI  - Application of mitomycin C after transoral removal of submandibular stones and
      sialodochoplasty.

PMID- 15867667
TI  - A new suction device in endolaryngeal laser surgery for simultaneous manipulation
      and cleaning.

PMID- 15867668
TI  - Modified minimal access surgery for MedEl and Clarion cochlear implants.

PMID- 15867669
TI  - Endoscopic sural nerve harvesting for facial nerve reconstruction.

PMID- 15867671
TI  - De novo bacterial reinfections after endoscopic sinus surgery: can uncinate
      process preservation surgeries prevent it?

PMID- 15867672
TI  - Duplicate publications in otolaryngology.

PMID- 15867674
TI  - Hey, nineteen.

PMID- 15867675
TI  - Should medical-surgical nursing experience be required for new graduates before
      working in a specialty? Writing for the pro position.

PMID- 15867676
TI  - Should medical-surgical nursing experience be required for new graduates before
      working in a specialty? Writing for the con position.

PMID- 15867677
TI  - Journey to Anna and Marie.
AB  - International adoptions are occurring in ever-increasing numbers in the United
      States. Nurses are providing care for families who have experienced international
      adoption and therefore would benefit from learning what the process entails. This
      article describes the experiences of one nurse who adopted two children from
      China. Her experiences can enrich other nurses and help them understand what a
      mother goes through when traveling to a foreign country to adopt a child.

PMID- 15867678
TI  - Nurses' knowledge, attitudes, and practices: regarding children's pain.
AB  - PURPOSE: To describe nurses' knowledge and attitudes about relieving children's
      pain, perceived barriers to optimal pain management, and analgesics administered
      by nurses in relation to levels of children's pain. STUDY DESIGN AND METHODS:
      Data were collected from 67 nurses and 132 children in their care. Outcomes were
      measured with The Nurses' Knowledge and Attitudes Survey Regarding Pain, the
      Nurses' Perceived Barriers to Optimal Pain Management for Children Survey,
      calculations of the ordered analgesia administered by the nurse, and the Oucher
      scale for intensity of children's pain. RESULTS: Most nurses demonstrated
      knowledge and positive attitudes about relieving children's pain but lacked
      knowledge about the incidence of respiratory depression and thought that children
      overreport their pain. Inadequate or insufficient physician medication orders for
      pain were identified by 99% of nurses as the greatest barrier to optimal pain
      management. The children's mean pain level was 1.63 (scale of 0 to 5). Of the 117
      children who reported pain, 74% received analgesia. Nurses administered means of
      37.9% of available morphine and 22.8% of available total analgesia. CLINICAL
      IMPLICATIONS: Nurses in practice need to become more aware of the adequacy of
      their analgesic administration, the value of children's self-report of pain, and
      the limitations of relying on children's behavioral manifestations to judge pain
      intensity. This study also demonstrates the importance of examining attitudes
      about children's pain relief and learning more about respiratory depression in
      children receiving opioids.

PMID- 15867679
TI  - Global maternal mortality: contributing factors and strategies for change.
AB  - As the 2004 Fulbright Scholar to the Russian Federation, Dr. Callister was asked
      to give this address at the Meetings of the International Commission on the
      Status of Women, United Nations, March 8, 2004, New York City. MCN is proud to be
      able to share this with its readers.

PMID- 15867681
TI  - Feeling normal. Women's experiences of menopause after infertility.
AB  - PURPOSE: To explore women's experiences of menopause after infertility. DESIGN:
      Grounded theory METHOD: Nine menopausal women, ranging in age from 48 to 72, with
      previous infertility, at various stages of the menopausal transition, including
      postmenopause, were interviewed in-depth. Three women had conceived a child after
      infertility treatment, three had adopted children, and three did not have
      children. The interviews were audiotaped and transcribed verbatim for data
      analysis. Data were constantly compared against other data, including previous
      transcripts, to look for evidence of data saturation. RESULTS: A core concept was
      generated, referred to as "finally feeling normal." After feeling abnormal during
      infertility, these women viewed menopause as a normal transition. They were able
      to reconcile some aspects of their infertility and embrace a feeling of normalcy.
      CLINICAL IMPLICATIONS: Menopause can be positive for women after infertility.
      Infertility contributed to a unique way of making meaning of menopause that was
      almost paradoxical: the notion that they can feel normal at the end of their
      "reproductive" years when they have struggled so long to actually be
      reproductive. Healthcare providers need to be cognizant of this possible response
      to menopause, and not automatically "pathologize" these women.

PMID- 15867682
TI  - Herb use in pregnancy: what nurses should know.
AB  - During the last decade, there has been a dramatic rise in the availability and
      use of medicinal herbal preparations. Childbearing women are among those who are
      asking nurses about herbal use, and therefore nurses need to learn more about
      this topic. One of the most important points to understand is that in the United
      States herbs are classified as dietary supplements (not drugs), and manufacturers
      are therefore not required to provide proof of efficacy or safety before selling
      these substances. Few studies about effects of herbs have been conducted in the
      general population, and fewer still have been published about pregnancy use.
      Because the perinatal nurse has two patients to consider when caring for a
      pregnant woman, he or she has two equally important mandates: to help the mother
      without harming the fetus. This article provides an overview of key concepts
      underlying herbal use in general and also safety in pregnancy. Common herbs that
      can be safely be used in pregnancy are presented in detail to enable the nurse to
      better care for the pregnant woman who is considering herbal use.

PMID- 15867684
TI  - The perinatal: special care unit: expert care for high-risk patients.
AB  - Labor and delivery units are often used to provide care for nonlaboring patients
      requiring intensive medical and nursing care. The utilization of labor beds in
      this manner, however, can result in a shortage of beds for those patients who are
      truly in labor. Unfortunately, patient dissatisfaction, use of supplemental
      staffing, and ill-prepared, overworked nurses can then become the result of this
      practice. Clearly, an improved, innovative model of providing care for high-risk
      perinatal patients is needed. The purpose of this article is to describe how one
      hospital and its interdisciplinary team met the challenge of providing expert
      care for complex perinatal patients by creating a unique model of patient care
      delivery, the perinatal special care unit (PSCU). An advanced practice nursing
      role, the perinatal nurse practitioner (PNNP) was implemented to provide
      collaborative care for these patients. This article includes a discussion of
      positive and negative outcomes that occurred after the PSCU became a reality.
      Overall, housing patients on the PSCU has eliminated inappropriate use of labor
      and delivery beds and has led to a more satisfying childbearing experience for
      all involved.

PMID- 15867685
TI  - Fat-soluble vitamins E and K.

PMID- 15867686
TI  - Human patient simulators in maternal-child nursing.

PMID- 15867693
TI  - Emergency drills in obstetrics.

PMID- 15867694
TI  - The Braden Scale for Predicting Pressure Sore Risk: reflections on the
      perioperative period.

PMID- 15867696
TI  - Leadership: able, willing, and available.

PMID- 15867697
TI  - Preparing a grant proposal-part 2: reviewing the literature.

PMID- 15867698
TI  - What treatments are effective for the management of peristomal hernia?

PMID- 15867699
TI  - The ramifications of perspective: how theory focuses research, data, and
      practice.
AB  - BACKGROUND: Although theoretical perspectives may be traced from theory to
      everyday life, the reverse is also true. In this article, the author explores how
      subdisciplines within nursing perceive and approach the clinical problem of
      incontinence in elderly persons. OBJECTIVE: To examine the relationship among the
      perception of clinical problems, various theoretical perspectives considered
      pertinent to the research to resolve these problems, different approaches to the
      research, and different research 'products.' APPROACH: In everyday life, we may
      trace beliefs, opinions, and behaviors back to their theoretical perspectives.
      The author uses a fictitious everyday conversation among 3 nurse researchers and
      a clinician as they discuss a scenario from literature regarding incontinence in
      the homecare of the elderly and suggests various research alternatives to
      approach the problem. RESULTS: Although nursing subscribes to a holistic
      perspective of the person, the scope of a holistic perspective cannot be
      accommodated within a single research approach. Specialization in nursing results
      in various priorities for approaching the problem of incontinence, resulting in
      different research agendas, different goals, and different outcomes. DISCUSSION:
      These divergent perspectives-arising within a single discipline-compete for
      research funding, for political attention and for policy recommendations.

PMID- 15867700
TI  - Development, implementation, and evaluation of a continence education package in
      acute and subacute care settings.
AB  - OBJECTIVE: The objective of the study was to trial and evaluate the effect that a
      discharge Continence Education Package (CEP) had on patients' continence
      awareness and management preferences. DESIGN: An exploratory descriptive design
      was used. SETTINGS AND SUBJECTS: A total of 631 participants were included in the
      study: 352 females (55.8%) and 279 males (44.2%) from 4 rural and regional
      settings in Victoria, Australia. INSTRUMENTS AND METHODS: A specifically designed
      questionnaire was used to assess participants' knowledge of incontinence and its
      management and also to investigate their treatment preferences and intentions if
      they experienced this type of problem. Data were collected at 2 time periods.
      Specifically, patients were interviewed before discharge from acute and subacute
      settings identified as Time 1 (T1). Then the participants were given the CEP and
      asked to complete a similar questionnaire. RESULTS: The findings revealed that
      fewer than 25% of participants had received information on continence before the
      study being conducted, yet the majority had indicated that they had experienced
      continence symptoms. The majority of participants found the CEP easy to
      understand (98.2%) and helpful (95.3%). Most participants said it provided them
      with information about types of actions to take and/or treatment options for
      incontinence problems. It also raised their awareness of the signs and symptoms
      associated with incontinence and provided them with a useful self-administered
      gauge with which to assess their continence status. CONCLUSIONS: These findings
      suggest that the CEP may be a useful educational tool for use in the general
      population.

PMID- 15867701
TI  - Research comparing three heel ulcer-prevention devices.
AB  - OBJECTIVE: To compare 3 pressure-reduction devices for effectiveness in
      prevention of heel ulcers in moderate-risk to high-risk patients. DESIGN: A
      prospective quasi-experimental 3-group design was used. SETTING AND SUBJECTS: A
      sample of 338 "moderate-risk to high-risk" adult inpatients, ages 18 to 97, at 2
      medical centers in South Texas were studied. INSTRUMENTS: The Braden Scale for
      Pressure Ulcer Risk and investigator-developed history and skin assessment tools
      were used. METHODS: Subjects were randomly assigned to the High-Cushion Kodel
      Heel Protector (bunny boot), Egg Crate Heel Lift Positioner (egg crate), or EHOB
      Foot Waffle Air Cushion (foot waffle). Data are demographics, Braden scores,
      comorbidities, skin assessments, lengths of stay, and costs of devices. Analyses
      were Chi-square, analysis of variance, and regression. RESULTS: Of 240 subjects
      with complete data, 77 (32%) were assigned to the bunny boot group, 87 (36.3%) to
      the egg crate, and 76 (31.7%) to the foot waffle. Twelve ulcers developed in 240
      subjects (5% incidence). Six subjects had only 1 foot. Eleven ulcers were Stage I
      (nonblanchable erythema), and 1 was Stage II (partial thickness). Overall
      incidence was 3.9% for the bunny boot, 4.6% for the egg crate, and 6.6% for the
      foot waffle (not significantly different among groups). The bunny boot with
      pillows was most cost effective (F[3], N = 240) = 1.342, p <or= .001).
      CONCLUSIONS: In this study, the bunny boot was as effective as higher-tech
      devices. The results, however, were confounded by nurses adding pillows to the
      bunny boot group.

PMID- 15867702
TI  - Sexuality and the person with a stoma: implications for comprehensive WOC nursing
      practice.
AB  - Pelvic surgery for bladder, colon, prostate, and gynecologic cancers or disease
      amelioration can affect sexual health and functioning for the long-term or short
      term. A person with a permanent diversion is likely to experience longer term
      adjustment challenges and may suffer from serious sexual dysfunction. Wound,
      ostomy, and continence nurses caring for the whole person must consider this in
      their overall care plan. Being prepared with specific information and practical
      interventions can assist in this endeavor. This article targets sexuality issues
      for a person with an ostomy and provides suggestions for comprehensive nursing
      interventions.

PMID- 15867704
TI  - Addressing the challenge of providing nursing care for elderly men suffering from
      urethral erosion.
AB  - Urethral erosion in the male patient with a long-term indwelling catheter is a
      known but poorly documented sequelae of catheter injury. It is a difficult and
      challenging problem for staff, the patient, and his family. Urethral erosion
      affects not only the complexity of the patient's care but also the patient's
      quality of life. In recent months, 3 elderly gentlemen who were living in 3
      different long-term care facilities were referred to us for assistance with their
      wounds, which were a direct result of catheter-related urethral erosion. In an
      attempt to find a solution for these difficult-to-manage wounds, the authors
      conducted a review of the literature. It quickly became evident that although
      literature is available describing urethral erosion and its relationship to
      indwelling urethral catheters, there is no literature available that describes
      the treatment and management of wounds caused by urethral erosion. Realizing that
      a solution to the problem or treatment of urethral erosion could not be found in
      the literature, the authors developed a treatment option for the management of
      urethral erosion. This article describes the plan of care devised to treat these
      3 male patients with urethral erosion. Through the use of soft silicone foam and
      soft silicone tape, a treatment plan was devised that removed the pressure,
      decreased catheter movement, and provided a moist wound healing environment.

PMID- 15867705
TI  - The future of healthcare: home is where the health is.

PMID- 15867706
TI  - Is the Incontinence Impact Questionnaire short form (IIQ-7) a clinically useful
      tool for WOC nursing practice?

PMID- 15867707
TI  - The role of intermediaries: getting evidence into practice.

PMID- 15867708
TI  - Accuracy and quality in the nursing documentation of pressure ulcers: a
      comparison of record content and patient examination.
AB  - OBJECTIVE: To determine the accuracy and describe the quality of nursing
      documentation of pressure ulcers in a hospital care setting. DESIGN: A cross
      sectional survey was used comparing retrospective audits of nursing documentation
      of pressure ulcers to previous physical examinations of patients. SETTING AND
      SUBJECTS: All inpatient records (n = 413) from February 5, 2002, at the
      surgical/orthopedic (n = 144), medical (n = 182), and geriatric (n = 87)
      departments of one Swedish University hospital. INSTRUMENTS: The European
      Pressure Ulcer Advisory Panel data collection form and the Comprehensiveness In
      Nursing Documentation. METHODS: All 413 records were reviewed for presence of
      notes on pressure ulcers; the findings were compared with the previous
      examination of patients' skin condition. Records with notes on pressure ulcers (n
      = 59) were audited using the European Pressure Ulcer Advisory Panel and
      Comprehensiveness In Nursing Documentation instruments. RESULTS: The overall
      prevalence of pressure ulcers obtained by audit of patient records was 14.3%
      compared to 33.3% when the patients' skin was examined. The lack of accuracy was
      most evident in the documentation of grade 1 pressure ulcers. The quality of the
      nursing documentation of pressure ulcer (n = 59) was generally poor. CONCLUSIONS:
      Patient records did not present valid and reliable data about pressure ulcers.
      There is a need for guidelines to support the care planning process and
      facilitate the use of research-based knowledge in clinical practice. More
      attention must be focused on the quality of clinical data to make proper use of
      electronic patient records in the future.

PMID- 15867709
TI  - The challenge of obtaining continence in a child with a neurogenic bowel
      disorder.
AB  - Fecal incontinence in pediatrics can occur from an array of conditions. A
      challenging group of pediatric patients are those with a neurogenic bowel
      disorder who can face a lifelong struggle with attaining and maintaining
      continence. It is difficult to develop a "cookbook approach" to care,
      particularly because these children's unique physical needs change as they
      develop. In addition to addressing physical needs, children's emotional and
      developmental needs must also be incorporated into the plan of care. This article
      provides an overview of the common congenital conditions in children with a
      neurogenic bowel, reviews assessment, and addresses treatment options that should
      be considered when developing a bowel management program.

PMID- 15867710
TI  - Modern management of nonneurologic pediatric incontinence.
AB  - Incontinence affects 20%-30% of children. Historically, evaluation of voiding
      problems in children has involved complete urodynamic studies and treatment based
      primarily on bladder findings and anticholinergic medications. Unfortunately,
      success with this approach has been poor. This article describes new advances in
      our understanding of the causes of nonneurologic pediatric incontinence and its
      associated problems and provides new treatment strategies to manage these
      patients. A strategy incorporating an escalating approach to evaluation and
      treatment is the cornerstone of this approach. Minimizing the routine use of
      invasive studies and medication is the result.

PMID- 15867711
TI  - A pilot study to evaluate reusable absorbent body-worn products for adults with
      moderate/heavy urinary incontinence.
AB  - OBJECTIVE: The purpose of this pilot study was to evaluate the performance of
      reusable absorbent body-worn products for adults with moderate/heavy urinary
      incontinence, compare their performance with a group of equivalent disposable
      products, and establish the need for a larger statistically robust study. SETTING
      AND SUBJECTS: Ten men and 4 women living in the community were recruited from
      locations throughout the United Kingdom. METHODS: A randomized multiple crossover
      design was used in which all subjects were given the opportunity to test each
      product. All the products were available on the UK market in January 2001. The
      following tools were used in the evaluation: a product performance questionnaire
      and a pad leakage diary. Overall opinion was used as the primary outcome
      indicator. RESULTS: The reusable Paddy T was the best performing product overall,
      outperforming the disposable products. For low leakage and good absorbency (the
      most important product attributes identified by the subjects), the disposable all
      in-one product performed best during the day. However, the Paddy T performed best
      for night use. The remaining reusable products performed poorly overall.
      CONCLUSIONS: Reusable products for moderate/heavy incontinence remain unpopular
      for use in isolation. Surprisingly, a product manufactured from terry toweling, a
      traditional material, performed relatively well. Reusables may provide a useful
      alternative to disposable products in certain circumstances. The results from
      this study do not support a more comprehensive costly study.

PMID- 15867712
TI  - Behavioral therapies at the primary care level: the current state of knowledge.
AB  - Urinary incontinence, the complaint of any involuntary loss of urine, is a
      troubling symptom experienced by men and women of all ages. Options for treatment
      include a range of behavioral, pharmacologic, and surgical therapies. Behavioral
      therapies, such as dietary modification, pelvic floor muscle training, and
      bladder training, are noninvasive, with little risk of side effects, and experts
      agree they should represent the first line of treatment whenever possible. These
      therapies can be initiated and monitored at the primary care level, thereby
      enhancing the accessibility of care for those affected. The purpose of this
      article is to methodically review what is and is not known about behavioral
      therapies, with attention to research needs. Although there is clear evidence for
      pelvic floor muscle training in women with urinary incontinence and modest
      evidence in men for a short time after radical prostatectomy, less is known about
      bladder training, prompted voiding, habit retraining, and timed voiding.
      Additional research is required to enhance our understanding of the comparative
      efficacy of behavioral interventions in specific populations. This research must
      take an increasingly long-term focus, given the potentially chronic nature of
      urinary incontinence.

PMID- 15867714
TI  - WOC nurses as advocates for patients who are morbidly obese: a case study
      promoting the use of bariatric beds.
AB  - Wound, ostomy, and continence nurses and healthcare providers are encountering
      more than ever before patients who are morbidly obese. Patients who are immobile
      and morbidly obese are at increased risk for complications such as skin
      breakdown. Strategies to predict and prevent skin and wound complications should
      include properly sized bariatric beds. Bariatric beds greatly reduce the risk of
      pressure ulcers through pressure reduction. They also promote patient
      independence, improve clinical outcomes, decrease staff workload, and help
      control unnecessary healthcare costs. The purpose of this article is to increase
      wound, ostomy, and continence nurses' awareness about the benefits of bariatric
      beds and some important issues that surround their use.

PMID- 15867719
TI  - The value of a WOCN.

PMID- 15867722
TI  - What interventions are effective for managing peristomal pyoderma gangrenosum?

PMID- 15867723
TI  - Can decision support improve nurses'use of knowledge?

PMID- 15867724
TI  - Assessment and treatment of depression: a review in high-risk populations.

PMID- 15867727
TI  - Pain in chronic leg ulcers.
AB  - OBJECTIVES: Describe the characteristics of pain in patients with chronic leg
      ulcers, correlate these descriptions with the characteristics of the ulcers and
      with patients' sociodemographic data, and determine the measures used for pain
      management. DESIGN: Descriptive and cross-sectional study with quantitative
      approach. SETTING AND SUBJECTS: The convenience sample was composed of 90
      patients with chronic leg ulcers drawn from 4 outpatient departments in Sao Paulo
      and Curitiba. INSTRUMENTS: Intensity and quality of patients' pain were
      determined using a 0-10 numeric pain intensity rating scale and a short version
      of the McGill Pain Questionnaire. METHODS: After gaining ethics committee
      approval, patients were selected during their ambulatory visits and interviewed
      by researchers. Data obtained were analyzed using the Kolmogorov-Smirnov
      Normality test, Mann-Whitney test, Chi-Square test, and Spearman's Correlation
      coefficient. RESULTS: Seventy-three (81.11%) patients had venous ulcers. The mean
      pain intensity reported was 3.10 (SD = 3.15), the mean intensity of the "worst
      pain of the week" was 7.56 (SD = 2.96), and the mean intensity of the "best pain
      of the week" was 2.05 (SD = 2.37). The McGill Questionnaire showed that sensitive
      descriptors were most frequently used to describe the pain. Statistically
      significant correlations (P < .05) were observed. The most intense pain was
      reported in subjects from the lowest income bracket studied and female gender and
      was correlated with alterations in sleep, movement, walking, and mood.
      Nonsteroidal antiinflammatory drugs were most commonly used (70%) for pain
      management. CONCLUSIONS: This study indicates the need for more attention and
      understanding on the part of healthcare workers regarding leg ulcer pain and its
      characteristics and the need for specific and effective procedures designed to
      contribute to the improvement in quality of life of these individuals.

PMID- 15867728
TI  - Bladder exstrophy: neonatal care and surgical approaches.

PMID- 15867729
TI  - Bladder exstrophy: a challenge for nursing care.

PMID- 15867730
TI  - Removal of short-term indwelling urethral catheters: the evidence.
AB  - OBJECTIVE: The objective of this systematic review was to determine the effect of
      the timing of removal of indwelling urethral catheters (IUCs) on the duration to
      and volume of first void, length of hospitalization, number of patients
      developing urinary retention and requiring recatheterization, patient
      satisfaction, and the percentage of IUCs removed according to the scheduled time
      for removal. MATERIALS AND METHODS: Published and unpublished literature in
      English and other languages between January 1966 and June 2002, which compared
      the effects of the timing of removal of short-term indwelling urethral catheters
      on patient outcomes, was systematically reviewed using multiple electronic
      databases. To determine eligibility of the trials for inclusion in the review,
      assessment of methodologic quality and data extraction was undertaken
      independently by 2 reviewers and verified by a third reviewer. Odds ratio (OR)
      for dichotomous data and a weighted mean difference for continuous data were
      calculated with 95% confidence intervals (CI). Where synthesis was inappropriate,
      a narrative overview has been undertaken. RESULTS: Eight randomized controlled
      trials were eligible for this review. When IUCs were removed at midnight, the
      time to first void was significantly shorter (P = .012) after gynecologic surgery
      and significantly longer in patients after urologic surgery and procedures. Seven
      trials reported that the volume of the first void was greater in patients whose
      IUCs were removed late at night, and this was statistically significant in 4
      trials. Patients who had their IUC removed at midnight were discharged from the
      hospital significantly (P < .00001) earlier than those who had their IUC removed
      in the morning, a finding that could result in potential cost savings for
      hospitals. CONCLUSION: Based on the limited available evidence, this article
      suggests benefits in terms of patient outcomes and reduction in the length of
      hospitalization after midnight removal of the IUCs. Further trials should be
      undertaken in wider settings and on specific groups of patients to enhance
      generalizability.

PMID- 15867731
TI  - Incontinent ileovesicostomy: a case study.

PMID- 15867736
TI  - Time for reviewing.

PMID- 15867737
TI  - Is negative pressure wound therapy effective for the management of chronic
      wounds?

PMID- 15867738
TI  - Does the workplace influence nurses' use of research?

PMID- 15867739
TI  - The prevalence of pressure ulcers in a tertiary care pediatric and adult
      hospital.
AB  - OBJECTIVE: To describe the pressure ulcer prevalence, stage and body location,
      and demographic characteristics of patients with pressure ulcers at a tertiary
      care adult hospital and a tertiary care pediatric hospital. DESIGN: Prevalence
      survey. SETTING AND SUBJECTS: A total of 513 inpatients, including 416 adults
      admitted to a tertiary care hospital and 97 children admitted to a tertiary care
      pediatric hospital. Only inpatients with mental health-related diagnoses were
      excluded. INSTRUMENTS: The Kinetics Concepts International's Prevalence and
      Incidence Study Collection Form was used to assess variables, including
      demographic information; presence, location, and stage of pressure ulcers; and
      presence of special support surfaces. METHODS: All patients had head-to-toe skin
      assessments performed during an 8-hour period by teams of 3 multidisciplinary
      staff members. Kinetics Concepts International's Prevalence and Incidence Program
      software and Microsoft Excel were used for data entry and analysis. RESULTS:
      Combined pressure ulcer prevalence was 26.3%, with 29.2% in adult patients and
      13.1% in pediatric patients. The most common body locations for pressure ulcers
      were the sacrum (22.1%), heels (14.8%), ears (12.9%), elbows (10.6%), and the
      buttocks (6.8%). Forty-eight percent of the ulcers were stage I, 36% Stage II, 6%
      Stage III-IV, and 10% unable to stage. CONCLUSIONS: Overall combined pressure
      ulcer prevalence and common body locations were consistent with findings from
      comparable hospitals. Patients at the extreme ends of the age spectrum had an
      increased risk of pressure ulcers. Stage I and II ulcers occurred most
      frequently. Potential prevention and early management strategies may be effective
      in decreasing the prevalence of these ulcers.

PMID- 15867741
TI  - A pilot study assessing the effectiveness of a glycerin suppository in controlled
      colostomy emptying.
AB  - The focus of this research was to explore another way for the patient to manage
      their colostomy. It was hoped that by inserting a glycerin suppository into the
      colostomy one would be able to evacuate the lower large intestine more
      effectively and efficiently. OBJECTIVE: To determine if persons with a sigmoid
      colostomy could obtain fecal continence by instituting a daily self-administered
      bowel-stimulating suppository. DESIGN: Randomized crossover comparative study
      comparing usual ostomy emptying practice with emptying with a glycerine
      suppository to stimulate controlled emptying. SETTING AND SUBJECTS: Adult males
      and females with a sigmoid colostomy were studied in their homes. INSTRUMENTS:
      The instruments included a profile questionnaire, a take-home diary, crossover
      and end-of-study questionnaires, and an exit questionnaire. METHODS: Subjects
      were randomized to their usual pouching method or to the experimental suppository
      method for 14 days each. RESULTS: There was no difference in fecal output, fecal
      volume, or flatus between the 2 groups. The action of the suppository was
      affected by its failure to remain in the bowel for an adequate amount of time.
      CONCLUSION: Further research is needed to determine if an adjunct device/method
      to hold the suppository in place would produce successful results.

PMID- 15867742
TI  - Female pelvic floor health: a developmental review.
AB  - An often neglected but important area of women's health involves the pelvic
      floor. Pelvic floor health can be reviewed by examining phases of a woman's life.
      Because pelvic floor health is not readily discussed and few professionals are
      considered experts in this area, it is often overlooked in women's healthcare. In
      medicine, care of the pelvic area can become fragmented as it is divided among
      urologists, gynecologists, and colorectal surgeons. The specialty of
      urogynecology combines 2 of the areas, and some physical therapists and nurses
      choose to specialize in female pelvic floor health. The issues of pelvic floor
      health are often addressed only after symptoms have presented. However, healthy
      practices can enhance pelvic floor well-being and maintain quality of life as a
      woman ages. This article is a review of clinical, research, and editorial
      articles on female pelvic floor issues and a discussion of measures that can
      contribute to optimal pelvic floor health.

PMID- 15867743
TI  - Evaluation of an electronic monitoring device for urinary incontinence in elderly
      patients in an acute care setting.
AB  - AIM: The primary aim of this study was to determine whether the use of habit
      training with an electronic monitoring device is better than standard habit
      training in the assessment and management of urinary incontinence in elderly
      patients in acute care hospitals. The second aim was to describe nurses'
      perceptions of continence management in acute care settings. DESIGN: A randomized
      controlled trial was conducted for an 18-month period. SAMPLE AND SETTING: The
      sample consisted of 41 elderly incontinent patients who resided on the acute care
      rehabilitation wards of 2 western Australian hospitals. INSTRUMENTS: A continence
      assessment form was used to document self-reported or carer-reported frequency
      and severity of incontinence. A continence monitoring chart was used to record
      voiding patterns and continence outcomes. A semi-structured interview guide was
      developed to elicit nurses' perceptions of continence management. RESULTS:
      Findings revealed no significant improvements in the self-reported or carer
      reported frequency of incontinence from baseline to follow-up of in-patients and
      at 1 month after discharge, although there was a trend toward improvement in both
      the experimental and the control groups at the posttest time points. A
      significant reduction in self-reported or carer-reported severity of incontinence
      was demonstrated in the experimental group at 1 month follow-up (P =
      5.025).Nurses' perceptions of continence management of elderly patients in acute
      care settings ranged from positive to extremely negative. Even those with
      positive perceptions were challenged by problems with device malfunction,
      perceptions of lack of time, lack of support from other staff, and lack of
      knowledge about how best to meet the continence management needs of this complex
      group of patients. CONCLUSION: The potential value of an electronic monitoring
      device for reducing incontinence could not be adequately assessed because of the
      small sample size and problems with the device and with implementing the study
      protocol. Although it was possible to determine a pattern in voiding times using
      the electronic device, compliance with the toileting regimen was difficult to
      achieve.Researchers and clinicians planning future studies with this device
      should be aware of the practical limitations associated with habit-training
      regimens for elderly patients in the acute care setting.

PMID- 15867746
TI  - Anesthesia for resection of spinal meningioma during pregnancy.

PMID- 15867744
TI  - Abdominal wound with a fistula and large amount of drainage status after
      incarcerated hernia repair.

PMID- 15867747
TI  - Prosthodontic principles in the framework design of maxillary obturator
      prostheses. 1989.

PMID- 15867748
TI  - Use of an alternative pontic foundation technique for a fiber-reinforced
      composite fixed partial denture: a clinical report.
AB  - This article describes the treatment of a patient for whom a fiber-composite
      laminate dowel and core and polyethylene fiber were used as a conservative
      alternative to provide a dowel-and-core and fixed partial denture foundation. The
      treatment plan included removing the existing restoration on the maxillary right
      first molar, placing a fiber-reinforced resin dowel and core for retention and
      reinforcement of the maxillary first premolar, and fabricating a definitive
      restoration using polyethylene fiber to reinforce the fixed partial denture.

PMID- 15867749
TI  - Conversion of a removable partial denture to a transitional complete denture: a
      clinical report.
AB  - A procedure is described for conversion of an existing removable partial denture
      into a complete denture using autopolymerizing tooth-colored acrylic resin,
      acrylic resin denture repair material, and a clear matrix template. The shape,
      color, and position of the lost natural teeth may be duplicated in the
      transitional denture, minimizing the psychological concerns of the patient
      regarding esthetics and social impact. Because the patient is never without
      teeth, an appropriate healing time can occur before fabrication of the definitive
      prosthesis.

PMID- 15867750
TI  - Early prosthetic treatment of patients with ectodermal dysplasia: a clinical
      report.
AB  - Hypohidrotic ectodermal dysplasia is a hereditary disorder of ectodermal origin.
      The early orthodontic treatment of 2 young boys suffering from hypohidrotic
      ectodermal dysplasia with partial maxillary and complete mandibular anodontia of
      the primary dentition is described. Both were treated with removable maxillary
      partial and mandibular complete dentures with individualized occlusion and age
      appropriate artificial teeth. The results were significant improvements in
      speech, masticatory function, and facial esthetics, contributing to the
      development of normal dietary habits, and the improved and more rapid social
      integration of these children.

PMID- 15867751
TI  - Stress distribution in fiber-reinforced composite inlay fixed partial dentures.
AB  - STATEMENT OF PROBLEM: Fiber-reinforced composite inlay fixed partial dentures
      (FRCIFPDs) may be a reliable prosthetic solution. Clinical procedures involved in
      their fabrication have been defined, but little is known about their mechanical
      behavior. PURPOSE: This in vitro study used the finite element (FE) method to
      investigate 3-dimensional (3-D) stress and strain distribution produced in a 3
      unit FRCIFPD. MATERIAL AND METHODS: A 3-D FE model (227,768 3-D tetrahedral
      elements) of a 3-unit FRCIFPD cemented onto box-shaped prepared teeth was
      developed. Stress and strain distribution generated by a maximum load of 196 N
      applied vertically or laterally to the FRCIFPD centrally, on an area of 4 +/- 0.1
      mm 2 , was analyzed. The specimen used to acquire the geometry of the model was
      also used for mechanical compressive tests, with vertical and lateral loads, to
      validate the numerical model. RESULTS: The peak values of stress, calculated on
      the outer and inner surfaces of the FRCIFPD, were localized in the connector
      areas. When a vertical load was applied, stress on the prepared teeth was
      concentrated at the cervical margin of the abutment preparation. CONCLUSION:
      Within the limitations of this in vitro study, the results suggest that within
      the FRCIFPD, stress concentrates at the connector areas, and that in the prepared
      teeth, peak stress is at the cervical margin of the box of the preparation.

PMID- 15867752
TI  - Indirect latex glove contamination and its inhibitory effect on vinyl
      polysiloxane polymerization.
AB  - STATEMENT OF PROBLEM: The inhibitory effect of indirect latex contamination on
      the polymerization of vinyl polysiloxane (VPS) impression material has been
      previously reported. However, the transfer of specific elements that cause
      inhibition has not been confirmed, nor has the removal of such contaminants been
      reported. PURPOSE: This study examined the surfaces of materials commonly used in
      restorative procedures that were contaminated by indirect latex glove contact and
      then evaluated for inhibition of polymerization of VPS. The effect of selected
      cleansing procedures was then studied. MATERIAL AND METHODS: Four experimental
      groups (n = 8) were prepared: (1) clean vinyl gloves (control), (2) clean
      gingival retraction cords (control), (3) contaminated vinyl gloves, and (4)
      contaminated gingival retraction cord. Microscopic evaluation of the appearance
      and the characterization of surface particulate contamination were performed for
      each. Three cleansing protocols were then evaluated for efficacy in cleaning
      vinyl glove surfaces contaminated by latex contact (n = 10): (1) brushing with
      water, (2) brushing with soap/rinsing with water, (3) cleansing with rubbing
      alcohol. The subsequent degree of VPS polymerization inhibition was evaluated
      subjectively. A chi-square test was used for data analysis (alpha=.05). RESULTS:
      Particulate sulfur elements and sulfur-chloride compounds were present on the
      contaminated substrates. None of the 3 cleansing procedures eliminated
      polymerization inhibition (P =.33). Residual elemental sulfur remained on all
      tested surfaces. CONCLUSION: Particulate sulfur and sulfur-chloride compounds
      were identified as the particulate contamination that resulted in polymerization
      inhibition of the tested VPS dental impression material. Removal of these
      contaminants from the tested vinyl gloves and gingival retraction cord was not
      possible with the 3 cleansing protocols tested in this study.

PMID- 15867753
TI  - Effect of an adhesive resin luting agent on the dowel-head retention of three
      different core materials.
AB  - STATEMENT OF PROBLEM: A dowel-and-core restoration may fail due to failure at
      either the dowel-tooth or dowel head-core material interface. Long-term clinical
      success of a dowel-and-core restoration depends on retention of both the dowel to
      the tooth and the dowel head to the core material. Thus, strengthening of the
      dowel head-core interface is important. PURPOSE: This study evaluated the
      retention between a prefabricated dowel and 3 different core materials with or
      without a dual-polymerized adhesive resin luting agent. MATERIAL AND METHODS:
      Sixty prefabricated dowels (Gold Plated Anchorage Post) were divided into 3
      groups (n=20) consisting of 1 of 3 core materials, amalgam (Standalloy F), light
      polymerized resin composite (Clearfil Ray), or glass ionomer (Chelon-Silver).
      Each core group was divided into 2 subgroups (n=10), and a dual-polymerized
      adhesive resin luting agent (Panavia F) was applied to the dowel heads of 1 of
      these subgroups before application of the core material. The manufacturing
      procedure was standardized by using a plastic index (4.5-mm internal diameter and
      5-mm height) and a custom-made dowel holder, which held the dowel head. Prepared
      specimens were stored in water at room temperature for 3 months and then loaded
      to fracture in a universal testing machine with a crosshead speed of 0.05 mm/min
      until failure. Bond strengths were recorded (MPa). Data were analyzed with 2-way
      analysis of variance (ANOVA) in a 2 x 3 factorial randomized design (alpha=.05).
      Afterward, core material differences were computed with 1-way ANOVA for both of
      the bonded and nonbonded groups. Post hoc multiple comparisons were made with the
      Dunnett C multiple range test. RESULTS: Dowel-head retention values (MPa) of the
      tested core materials (mean +/- SD) from the highest to the lowest were as
      follows: bonded amalgam core, 296.1 +/- 108; bonded composite core, 284.3 +/-
      38.3; nonbonded composite core, 177.0 +/- 53.7; nonbonded amalgam core, 128.5 +/-
      35.0; bonded glass-ionomer core (GIC), 128.0 +/- 24.5; nonbonded GIC, 61.8 +/-
      13.3. Two-way ANOVA revealed significant differences between the core material
      groups and between the bonded and nonbonded groups (P <.001). The interaction
      between the core material and bond variables was also significant (P =.018). One
      way ANOVA revealed statistically significant differences between the bonded (P
      <.001) and also between the nonbonded core material groups (P <.001). Post hoc
      multiple comparisons showed that the dowel-head retention of the GIC was
      significantly weaker than the post-head retention for amalgam and resin
      composite, whether bonded or not. CONCLUSION: Within the limitations of this
      study, the adhesive resin luting agent tested appeared to have a significant
      strengthening effect on the dowel-head retention of the core materials.

PMID- 15867754
TI  - An in vitro comparison of cast metal dowel retention using various luting agents
      and tensile loading.
AB  - STATEMENT OF PROBLEM: No clear consensus exists regarding the choice of luting
      agents for the retention of cast metal dowels used as a treatment alternative for
      endodontically treated teeth with excessive loss of coronal tooth structure.
      PURPOSE: The purpose of this in vitro study was to investigate the retention of
      the dowel/luting agent/tooth complex while applying different luting agents to
      cast metal dowels under vertical tensile loading. MATERIAL AND METHODS: Sixty
      extracted, noncarious mandibular premolars with roots of approximately 15-mm
      length were selected. For each tooth, a tapered root canal preparation was
      completed to a maximum diameter of 1.60 mm and a length of 11 mm, a common
      clinical configuration to accommodate cast metal dowels. Sixty cast metal dowels
      were fabricated for the tooth specimens and cemented with 1 of 3 luting agents (n
      = 20): zinc-phosphate cement (ZPC) as a control, phosphate-methacrylate resin
      luting agent (PMRL, Panavia F), and phosphate-methacrylate resin luting agent
      with metal dowel surfaces modified with a silane coating technique (PMRLS,
      Panavia F + Siloc). Tensile bond strength (TBS) of the specimens was measured
      with a universal testing machine at a crosshead speed of 0.5 mm/min. Data (kg)
      were statistically analyzed using a 1-way analysis of variance and a Scheffe
      multiple range test (alpha=.05). The homogeneity of variances was analyzed using
      the Levene test. RESULTS: The TBS values of ZPC (34.2 +/- 10.54 kg) were
      significantly higher than PMRL (22 +/- 9.57 kg) and PMRLS (21.7 +/- 7.64 kg).
      There was no significant difference between the PMRL and PMRLS groups.
      CONCLUSION: Within the limitations of this study, the use of zinc-phosphate
      cement provided greater TBS for cast metal dowels than the resin luting agent
      with and without the silane coating technique. The TBS values with and without
      the silane coating technique were not statistically different.

PMID- 15867755
TI  - Effects of various finishing procedures on the staining of provisional
      restorative materials.
AB  - STATEMENT OF PROBLEM: The color stability of tooth-colored restorative materials
      for provisional restorations is of primary importance when provisional prostheses
      are worn long term. However, the effect of different polishing methods on the
      color difference of provisional restorative (PR) materials has not been
      completely clarified. PURPOSE: The purpose of this study was to investigate the
      effect of different polishing methods on color stability of 2- and 3-component
      autopolymerized bis-acrylic composites, a light polymerized composite, and a
      methyl methacrylate-based PR material upon exposure to a staining agent. Material
      and methods Sixty cylindrical specimens (15 x 2 mm) were prepared for each of bis
      acryl composites (Protemp II and Luxatemp), a light-polymerized composite
      (Revotek LC), and a methyl methacrylate-based (TemDent) PR material by using a
      brass mold. The specimens were divided into 6 groups (n=10), and different
      polishing procedures were used, including pumice (P), diamond polishing paste
      (Dpp), polishing discs (Pd), and combinations of these. Unpolished specimens
      served as the control. The specimens were stored for 48 hours at 37 degrees C in
      a coffee solution. The color of all specimens was measured with a colorimeter
      (Minolta CR-300) before and after exposure, and color changes (DeltaE) were
      calculated. The data were analyzed with a 2-way analysis of variance, and mean
      values were compared by the Tukey Honestly Significant Difference test
      (alpha=.05). RESULTS: The provisional materials, surface polishing procedures,
      and interaction were significant (P <.05). In the light-polymerized composite
      group, the lowest color difference (DeltaE) was observed in Group P-Dpp (4.9) and
      Group P (5.3), which were not significantly different from each other. In the
      autopolymerized bis-acryl composites and the methyl methacrylate-based
      provisional materials, the lowest color difference (DeltaE) was observed in Group
      P-Dpp. The largest color difference for the light-polymerized and autopolymerized
      composites was observed in Group Pd-Dpp and Group Pd, which were not
      significantly different from each other. In the methyl methacrylate-based
      material group, the largest color difference was observed in Group Pd. When
      comparing the 4 different PR materials, the methyl methacrylate-based material
      group demonstrated statistically significantly less color change than the other
      provisional material tested. CONCLUSION: The methyl methacrylate-based PR
      material (TemDent) was found to be more color stable than the autopolymerized
      (Protemp II and Luxatemp) and light-polymerized (Revotek LC) composites tested.
      The use of diamond polishing paste after polishing with pumice significantly
      decreased the staining of methyl metacrylate and bis-acryl composites tested. The
      highest color-change values were obtained in the groups polished with polishing
      discs, which were found to be significantly different compared to values obtained
      with other polishing techniques.

PMID- 15867756
TI  - The effect of a layer of resin luting agent on the biaxial flexure strength of
      two all-ceramic systems.
AB  - STATEMENT OF PROBLEM: The influence of a layer of resin luting agent on the
      longevity of glass-ceramic crowns has been demonstrated in some laboratory and
      clinical studies. The mechanisms of glass-ceramic crown failure and the influence
      of the resin luting agent layer are still not clearly understood. PURPOSE: The
      objectives of this study were to examine the difference in biaxial flexure
      strength between 2 glass-ceramic dental materials and to examine the influence of
      a layer of resin luting agent on the characteristic strength of these materials.
      MATERIAL AND METHODS: Thirty-seven disks, 15 mm x 1.5 mm, each of IPS Empress and
      IPS Empress2, were fabricated according to the manufacturer's recommendations.
      The surface of each disk underwent acid etching and silanation. The disks from
      each group were arbitrarily divided into 2 subgroups. One subgroup of each
      material type was selected to receive a thin (approximately 0.1 mm) layer of
      resin luting agent (Nexus 2), whereas the other subgroups remained unaltered.
      Each disk was loaded, with the treated surface down, using a ball-on-ring biaxial
      configuration in a universal testing machine. The failure loads (N) were
      recorded, and the biaxial flexure strength for each disk was calculated.
      Characteristic Weibull parameters and a +/-95% confidence interval were
      determined. A 2-way analysis of variance (alpha=.05) on transformed fracture
      strength data was used to determine significant differences between groups.
      RESULTS: The Weibull characteristic strength of IPS Empress2 (213 MPa) was 75%
      higher than IPS Empress (122 MPa). The results also show that the application of
      a thin layer of resin luting agent significantly increased (P <.001) the
      characteristic strength of both IPS Empress and IPS Empress2 by 45.6% and 47.6%,
      respectively. The higher strength of the resin-coated specimens cannot be
      explained in terms of standard fracture mechanics alone. CONCLUSION: Results
      suggested that IPS Empress had significantly lower characteristic strength than
      IPS Empress2. A relatively thin layer of resin luting agent bonded to both IPS
      Empress and IPS Empress2 significantly increased the characteristic strength of
      the ceramics.

PMID- 15867757
TI  - Mathematical derivation of the minimally acceptable all-porcelain margin angle.
AB  - There is limited research defining the minimally acceptable porcelain margin
      angle required to withstand the stresses incurred during seating a restoration. A
      mathematical model was derived to calculate this critical porcelain margin angle.
      The factors involved in margin fracture were determined to be the tensile
      strength of the porcelain, the axial reduction, the diameter of the tooth, the
      porcelain margin angle, and the seating force. As the seating force increases,
      the porcelain margin angle required to prevent failure also increases. Increasing
      either the axial reduction or the diameter of the tooth allowed the minimum
      porcelain margin angle to decrease.

PMID- 15867758
TI  - Comparative study of the surface characteristics, microstructure, and magnetic
      retentive forces of laser-welded dowel-keepers and cast dowel-keepers for use
      with magnetic attachments.
AB  - STATEMENT OF PROBLEM: Information regarding the merits and problems associated
      with connecting a keeper to a dowel and coping using a laser welding technique
      has not been explored extensively in the dental literature. PURPOSE: This in
      vitro study compared the surface characteristics, microstructure, and magnetic
      retentive forces for a dowel and coping-keeper mechanism fabricated using a laser
      welding process and a cast-to casting technique. MATERIAL AND METHODS: Five cast
      to and 6 laser-welded dowel and coping-keeper specimens were tested. Using 5
      freestanding keepers as the control group, the surface characteristics and
      microstructures of the specimens were examined by means of stereomicroscopy,
      metallographic microscopy, and scanning electron microscopy (SEM). Energy
      dispersive spectroscopic (EDS) microanalysis with SEM provided elemental
      concentration information for the test specimens. The vertical magnetic retentive
      forces (N) of the 3 groups were measured using a universal testing machine. The
      results were statistically compared using 1-way analysis of variance and the
      Newman-Keuls multiple range test (alpha =.05). RESULTS: The laser-welded dowel
      keeper generally maintained its original surface smoothness as well as the
      original microstructure. Elements diffused readily through the fusion zone. The
      surface of the cast dowel-keeper became rough with the formation of an oxide
      layer, the microstructure changed, and there was only limited elemental diffusion
      in the fusion zone. The average vertical magnetic retentive force of the laser
      welded group, the cast group, and the control group were 4.2 +/- 0.2 N, 3.8 +/-
      0.3 N, and 5.6 +/- 0.3 N, respectively. Statistically significant differences in
      vertical magnetic retentive force were found between the control group and both
      the laser-welded and cast groups (P <.01). Compared with the cast dowel-keepers,
      the average vertical magnetic retentive force of the laser-welded dowel-keepers
      was significantly higher (P <.05). CONCLUSION: The laser welding technique had
      less influence on the surface characteristics, the microstructure, and the
      magnetic retentive forces of keepers relative to techniques that incorporate a
      keeper at the time of cast dowel and coping fabrication.

PMID- 15867759
TI  - Shear bond strength of resin composite to magnetic Fe-Pt alloy.
AB  - STATEMENT OF PROBLEM: It is important to obtain strong adhesion between resin
      composite material and magnetic Fe-Pt alloy for fabrication of an indirect
      veneered crown. However, little is known about the bond strength between these
      materials. PURPOSE: This study evaluated the bond strength of resin composite to
      magnetic Fe-Pt alloy, using 4 adhesive metal primers. MATERIAL AND METHODS:
      Seventy disk-shaped patterns (7.5 mm in diameter, 2.0 mm thick) were cast from a
      custom-made Fe-Pt ingot using a high-frequency centrifugal casting machine. After
      the bonding surfaces were airborne-particle abraded with 50 microm Al2O3,
      specimens were divided into groups (n=7) and primed with either Metal Primer II
      (MP), Meta Fast Bonding Liner (BL), New Meta Color INFIS Opaque Primer (IN), or
      Epricord Opaque Primer (EP). Nonprimed specimens served as controls (n=7). A
      resin composite (New Meta Color INFIS) was then applied to all specimens and
      polymerized. After the specimens were immersed in 37 degrees C water for 24 hours
      or thermal cycled at 4 degrees C to 60 degrees C with a 1-minute dwell time of up
      to 10,000 cycles, the shear bond strengths (MPa) were measured using a universal
      testing machine at a crosshead speed of 0.5 mm/min. The data were statistically
      analyzed by a 2-way analysis of variance and the Scheffe test (alpha=.05).
      RESULTS: Although IN had the lowest strength, there were no significant
      differences in bond strengths of the other 3 primers (MP, BL, and EP) before
      thermal cycling. The bond strengths of MP and EP were slightly altered by thermal
      cycling (P >.05); however, BL and IN underwent a significant decrease (P <.05).
      CONCLUSION: The results of this in vitro study indicate that MP and EP provide
      superior long-term shear strength when bonding the resin composite evaluated to
      Fe-Pt alloy.

PMID- 15867760
TI  - Effect of microwave sterilization and water storage on the Vickers hardness of
      acrylic resin denture teeth.
AB  - STATEMENT OF PROBLEM: Acrylic resin denture teeth soften upon immersion in water,
      and the heating generated during microwave sterilization may enhance this
      process. PURPOSE: Six brands of acrylic resin denture teeth were investigated
      with respect to the effect of microwave sterilization and water immersion on
      Vickers hardness (VHN). MATERIAL AND METHODS: The acrylic resin denture teeth
      (Dentron [D], Vipi Dent Plus [V], Postaris [P], Biolux [B], Trilux [T], and
      Artiplus [A]) were embedded in heat-polymerized acrylic resin within
      polyvinylchloride tubes. For each brand, the occlusal surfaces of 32 identical
      acrylic resin denture posterior teeth were ground flat with 1500-grit silicon
      carbide paper and polished on a wet polishing wheel with a slurry of tin oxide.
      Hardness tests were performed after polishing (control group, C), after polishing
      followed by 2 cycles of microwave sterilization at 650 W for 6 minutes (MwS
      group), after polishing followed by 90-day immersion in water (90-day Wim group),
      and after polishing followed by 90-day storage in water and 2 cycles of microwave
      sterilization (90-day Wim + MwS group). For each specimen, 8 hardness
      measurements were made and the mean was calculated. Data were analyzed with a 2
      way analysis of variance followed by the Bonferroni procedure to determine any
      significance between pairs of mean values (alpha=.01). RESULTS: Microwave
      sterilization of specimens significantly decreased (P <.001) the hardness of the
      acrylic resin denture tooth specimens P (17.8 to 16.6 VHN), V (18.3 to 15.8 VHN),
      T (17.4 to 15.3 VHN), B (16.8 to 15.7 VHN), and A (17.3 to 15.7 VHN). For all
      acrylic resin denture teeth, no significant differences in hardness were found
      between the groups MwS, 90-day Wim, and 90-day Wim + MwS, with the exception of
      the 90-day Wim + MwS tooth A specimens (14.4 VHN), which demonstrated significant
      lower mean values (P <.001) than the 90-day Wim (15.8 VHN) and MwS (15.7 VHN)
      specimens. CONCLUSIONS: For specimens immersed in water for 90 days, 2 cycles of
      microwave sterilization had no effect on the hardness of most of the acrylic
      resin denture teeth.

PMID- 15867761
TI  - The use of three different matrices to ensure proper spatial dimension in
      fabricating definitive implant-supported prostheses.
AB  - Implant concepts continue to evolve not only in terms of materials, surfaces, and
      designs but also in clinical experience and technical management. This article
      presents a clinical and laboratory procedure describing how to plan, ensure, and
      achieve proper spatial dimension in fabricating definitive implant-supported
      prostheses with the use of 3 different matrices. This will in turn aid in
      restoring the patient with a predictable outcome from the outset of the
      treatment.

PMID- 15867762
TI  - Use of wax spacers for putty-wash impression of implant snap-on impression
      copings.

PMID- 15867763
TI  - A modified bur for improved access to the implant analogue on the solid stone
      cast.

PMID- 15867764
TI  - A device to aid insertion of an implant screw.

PMID- 15867765
TI  - A swinglock removable partial denture aid for physically impaired individuals.

PMID- 15867766
TI  - Prosthetic aortic valve replacement.

PMID- 15867767
TI  - Evolving role of cardiovascular pathology in clinical and surgical decision
      making.

PMID- 15867768
TI  - The clinical development of percutaneous heart valve technology.

PMID- 15867769
TI  - Phase II trial of postoperative adjuvant cisplatin and etoposide in patients with
      completely resected stage I-IIIa small cell lung cancer: the Japan Clinical
      Oncology Lung Cancer Study Group Trial (JCOG9101).
AB  - OBJECTIVE: Indications for surgical intervention for very limited small cell lung
      cancer have not yet been determined. The objective of this study is to determine
      whether resection followed by cisplatin and etoposide is feasible. METHODS: From
      September 1991 through December 1996, 62 patients with completely resected small
      cell lung cancer who were less than 76 years of age from 17 centers were entered
      in the trial. Of 62 patients, 61 were eligible, with a median follow-up of 65
      months. Chemotherapy consisted of 4 cycles of cisplatin (100 mg/m 2 , day 1) and
      etoposide (100 mg/m 2 , days 1-3). There were 49 (80%) male patients, 44 with
      clinical stage I disease, 10 with stage II disease, and 6 with stage IIIa
      disease. RESULTS: Forty-two (69%) patients received 4 cycles of cisplatin and
      etoposide. No treatment-associated mortality was noted. Median survival time was
      not reached in patients with pathologic stage I disease, was 449 days in patients
      with stage II disease, and was 712 days in patients with stage IIIa disease.
      Three-year survival was 61% overall, 68% in patients with clinical stage I
      disease, 56% in patients with stage II disease, and 13% in patients with stage
      IIIa disease ( P = .02). Recurrence was noted in 26 (43%) patients overall. Local
      failure was noted in 6 (10%) patients. Locoregional recurrence tends to be found
      more frequently in patients with stage IIIA disease. Distant failure was found in
      21 (34%) patients overall. Brain metastasis was found in 15% of the patients.
      CONCLUSION: Major lung resection followed by postoperative cisplatin and
      etoposide is feasible, with a favorable survival profile. Because nodal
      metastasis appears to be a major prognostic factor, preoperative evaluation of
      nodal status remains a major concern.

PMID- 15867770
TI  - Surgical lung biopsy for diffuse pulmonary disease: experience of 196 patients.
AB  - OBJECTIVE: Surgical lung biopsy is considered the final method of diagnostic
      modality in patients with undiagnosed diffuse pulmonary disease. Nevertheless,
      the effect of surgical lung biopsy on the diagnosis, treatment, and outcome of
      the patient still remains controversial. This study reviewed the experiences of
      surgical lung biopsies in 196 consecutive patients during the past 7 years.
      METHODS: Surgical lung biopsy was performed after achievement of general
      anesthesia through video-assisted thoracoscopic surgery or a 7-cm
      minithoracotomy. Biopsy specimens were swabbed for aerobic and anaerobic
      bacterial, fungal, and mycobacterial cultures. The sections of specimens were
      routinely stained with hematoxylin and eosin, and acid-fast, Gomori methenamine
      silver, Gram stain, or other special stains were added if necessary. RESULTS: The
      pathologic diagnosis after surgical lung biopsy included infection (30.6%),
      interstitial pneumonia or fibrosis (21.9%), diffuse alveolar damage (17.3%),
      neoplasm (13.3%), autoimmune diseases (8.2%), and others (8.2%). After surgical
      lung biopsy, 165 (84.2%) patients had changes in their therapy, 124 (63.3%)
      patients had clinical improvement of their conditions, and 119 (60.7%) patients
      survived to hospital discharge. Comparison between immunocompromised and
      immunocompetent patients showed that diagnosis of infection was significantly
      higher ( P < .01) in the former group (41.2% vs 20.2%). In addition, there was no
      significant difference in the distribution of diagnosis and rate of change in
      therapy between the respiratory failure and nonrespiratory failure groups.
      However, the rates of response to therapy and patient survival were significantly
      lower in the respiratory failure group (51.2% and 41.5%) than in the
      nonrespiratory failure group (71.9% and 78.1%, P < .05). There was no surgical
      mortality directly related to the procedure. The surgical morbidity rate was
      6.6%. CONCLUSION: Surgical lung biopsy is a safe and accurate diagnostic tool for
      diffuse pulmonary disease. For a large proportion of the patients, change of
      therapy and then clinical improvement can be achieved after surgical lung biopsy.
      Surgical lung biopsy should be considered earlier in patients with undiagnosed
      diffuse pulmonary disease, especially when the respiratory condition is
      deteriorating.

PMID- 15867771
TI  - Limited resection trial for pulmonary ground-glass opacity nodules: fifty-case
      experience.
AB  - OBJECTIVE: This study was undertaken to determine the recurrence rate after
      limited resection of small lung carcinoma and to evaluate intraoperative frozen
      section examination accuracy for Noguchi classification. METHODS: Enrollment
      requirements were as follows: pulmonary nodule 2 cm or smaller, diagnosed or
      suspected clinical T1 N0 M0 carcinoma in the lung periphery, and ground-glass
      opacity findings and lack of evident pleural indentations or vascular convergence
      on high-resolution computed tomographic scan. A wedge or segmental resection
      specimen, removed with custom stapler cartridges, was immediately reinflated and
      examined by frozen-section with hematoxylin-eosin and Victoria blue-van Gieson
      stains. If the tumor was confirmed as Noguchi type A or B with resection margins
      greater than 1 cm, the patient was closed and followed up on an outpatient basis.
      End points were 5-year disease-free survival and intraoperative classification
      accuracy. RESULTS: From August 1998 through October 2002, a total of 50 patients
      were enrolled (20 men and 30 women, ages 30-77 years). Tumor sizes ranged from 2
      to 21 mm (11 mm average). There were 2 Noguchi type A tumors, 23 Noguchi type B
      tumors, 15 Noguchi type C tumors, 5 atypical adenomatous hyperplasias, 4
      fibroses, and 1 granuloma. Frozen-section accuracy was approximately 98% (39/40).
      One intraoperative type B diagnosis was revised to type C after postoperative
      pathologic study. No morbidity, mortality, or recurrence has been seen with a
      median follow-up of 50 months. CONCLUSION: Noguchi type A and B tumors may well
      be in situ carcinomas, and frozen-section examination was highly accurate.
      Neither local recurrence nor distant metastases have been found to date. Limited
      resection initial results appear promising.

PMID- 15867772
TI  - Pharmacologic prophylaxis for postoperative atrial tachyarrhythmia in general
      thoracic surgery: evidence from randomized clinical trials.
AB  - BACKGROUND: Atrial tachyarrhythmia is the most common complication after general
      thoracic surgery and is associated with significant morbidity, longer hospital
      stay, and higher costs. We sought to determine whether the use of antiarrhythmic
      medications is associated with a reduced rate of postoperative atrial
      tachyarrhythmia. METHODS: MEDLINE, EMBASE, Cochrane Database of clinical trials
      (1980-2003), and reference lists of relevant articles were searched for
      randomized controlled trials with placebo control, general thoracic patients, and
      noncombined and prophylactic use of the medications. Search, data abstraction,
      and analyses were performed and confirmed by at least 2 authors. A fixed-effects
      model was used to perform meta-analyses. RESULTS: There were 11 unique trials
      (total n = 1294) that met the inclusion criteria. Calcium-channel blockers and
      beta-blockers reduced the risk of atrial tachyarrhythmia in 4 and 2 trials,
      respectively (relative risk of 0.50 and 95% confidence interval of 0.34-0.73;
      relative risk of 0.40 and 95% confidence interval of 0.17-0.95, respectively).
      However, beta-blockers tended to increase the risk of pulmonary edema (relative
      risk, 2.15; 95% confidence interval, 0.74-6.23). Magnesium tested in one
      unblinded trial also reduced the risk of atrial tachyarrhythmia (relative risk,
      0.4; 95% confidence interval, 0.21-0.78). On the other hand, digitalis
      preparations were found to be harmful because they increased the risk of atrial
      tachyarrhythmia in 3 trials (relative risk, 1.51; 95% confidence interval, 1.00
      2.28). Finally, 2 other medications, flecainide and amiodarone, were each tested
      in a single small trial, and their effects were associated with great
      uncertainty. CONCLUSIONS: Calcium-channel blockers and beta-blockers are
      effective in reducing postoperative atrial tachyarrhythmia. The use of these
      medications should be individualized, and possible adverse events of beta
      blockers should be taken into account. Randomized clinical trials do not support
      the use of digitalis in general thoracic surgery. The value of magnesium as a
      supplement to a main prophylactic regimen should be explored.

PMID- 15867773
TI  - Laryngotracheoplastic resection for primary tumors of the proximal airway.
AB  - BACKGROUND: Primary tumors of the airway with proximity to vocal cords and
      recurrent laryngeal nerves can be resected with sparing of the larynx. Long-term
      data on survival and local recurrence after laryngotracheal resection are scarce.
      METHODS: We conducted a retrospective study of laryngotracheal resection and
      reconstruction for primary tumors of the airway since 1972. RESULTS: Twenty-five
      patients aged 15 to 77 years presented with adenoid cystic carcinomas (n = 9),
      squamous cell carcinomas (n = 6), and other airway tumors (n = 10). Subglottic
      resection consisted of anterior cricoid in 5 patients; posterior cricoid mucosa
      in 9 patients, with resection of the posterior cricoid plate in 3 patients;
      lateral resection in 7 patients; and combined anterior and posterior elements in
      4 patients. Vascularized trachea was tailored to reconstruct the defect. Seven
      patients without hoarseness required resection of the recurrent laryngeal nerve,
      and 4 other patients with hoarseness did not. There were no operative deaths. Two
      (8.0%) patients who had received prior high-dose cervical radiation had
      anastomotic separation, one requiring laryngectomy. One patient needed permanent
      tracheostomy, and temporary (<2 months) airway tubes were used in 5 patients.
      Sixteen patients received postoperative radiation. Median follow-up was 101
      months. Four (16%) patients died of disease. Overall survival at 5 and 10 years
      was 79% and 64%, respectively. No patient underwent laryngectomy for recurrence.
      CONCLUSION: Laryngotracheal resection and immediate reconstruction for subglottic
      tumors is achieved with good preservation of voice, low morbidity, and no
      compromise of long-term survival.

PMID- 15867774
TI  - The selective epidermal growth factor receptor tyrosine kinase inhibitor PD153035
      suppresses expression of prometastasis phenotypes in malignant pleural
      mesothelioma cells in vitro.
AB  - OBJECTIVE: Malignant pleural mesothelioma is notoriously refractory to aggressive
      multimodality therapy. Epidermal growth factor receptor expression has been
      observed on malignant pleural mesothelioma cells. Epidermal growth factor
      receptor-mediated signaling promotes tumorigenesis and metastasis of cancer
      cells. The purpose of this study is to evaluate the ability of the epidermal
      growth factor receptor tyrosine kinase inhibitor PD153035 to abrogate the
      expression of prometastasis phenotypes in malignant pleural mesothelioma cells in
      vitro. METHODS: Epidermal growth factor receptor expression of malignant pleural
      mesothelioma cells and primary normal cells was quantitated by means of flow
      cytometry. PD153035-mediated growth inhibition was determined by means of 1-(4,5
      Dimethylthiazol-2-yl)-3,5-diphenylformazan and clonogenic assays. Cell motility
      and invasion of extracellular matrix was evaluated with in vitro wound-healing
      and Matrigel invasion assays, respectively. Vascular epidermal growth factor
      levels in conditioned media were measured by using enzyme-linked immunosorbent
      assay. RESULTS: Epidermal growth factor receptor expression was detected on all 6
      cultured malignant pleural mesothelioma cells, with 4 of 6 having normal receptor
      expression and 2 of 6 overexpressing the receptor. PD153035 suppressed cell
      motility and cell invasion through a Matrigel membrane, regardless of the
      baseline epidermal growth factor receptor expression. Decreased vascular
      epidermal growth factor production and significant inhibition of growth only
      occurred in malignant pleural mesothelioma cells that overexpress epidermal
      growth factor receptor. CONCLUSIONS: Epidermal growth factor receptor tyrosine
      kinase inhibitor PD153035 significantly inhibited motility and invasion in
      malignant pleural mesothelioma cells in vitro, regardless of their epidermal
      growth factor receptor expression levels. Inhibition of epidermal growth factor
      receptor-dependent signaling might be a useful strategy to diminish malignant
      pleural mesothelioma recurrence after aggressive cytoreductive surgery.

PMID- 15867775
TI  - Modern surgical treatment of massive pulmonary embolism: results in 47
      consecutive patients after rapid diagnosis and aggressive surgical approach.
AB  - OBJECTIVES: This study retrospectively reviews an aggressive multidisciplinary
      approach to the treatment of massive pulmonary embolism, centering on rapid
      diagnosis with contrast-enhanced computed tomography of the chest to define the
      location and degree of clot burden and transthoracic echocardiography to document
      right ventricular strain followed by immediate surgical intervention when
      appropriate. METHODS: Between October 1999 through February 2004, 47 patients (30
      men and 17 women; median age, 58 years; age range, 24-86 years) underwent
      emergency surgical embolectomy for massive central pulmonary embolism. The
      indications for surgical intervention were (1) contraindications to thrombolysis
      (21/47 [45%]), (2) failed medical treatment (5/47 [10%]), and (3) right
      ventricular dysfunction (15/47 [32%]). Preoperatively, 12 (26%) of 47 patients
      were in cardiogenic shock, and 6 (11%) of 47 were in cardiac arrest. RESULTS:
      There were 3 (6%) operative deaths, 2 with preoperative cardiac arrest; 2 of
      these 3 patients required a right ventricular assist device. In 38 (81%) patients
      a caval filter was placed intraoperatively. Median length of stay was 11 days
      (range, 3-75 days). Median follow-up was 27 months (range, 2-50 months); follow
      up was 100% complete in surviving patients. There were 6 (12%) late deaths, 5 of
      which were from metastatic cancer. Actuarial survival at 1 and 3 years' follow-up
      was 86% and 83%, respectively. CONCLUSION: An aggressive approach to large
      pulmonary embolus, including rapid diagnosis and prompt surgical intervention,
      has improved results with surgical embolectomy. We now perform surgical pulmonary
      embolectomy not only in patients with large central clot burden and hemodynamic
      compromise but also in hemodynamically stable patients with right ventricular
      dysfunction documented by means of echocardiography.

PMID- 15867776
TI  - Is early anticoagulation with warfarin necessary after bioprosthetic aortic valve
      replacement?
AB  - OBJECTIVES: Freedom from anticoagulation is the principal advantage of
      bioprosthesis; however, the American Heart Association/American College of
      Cardiology and the American College of Chest Physicians guidelines recommend
      early anticoagulation with heparin, followed by warfarin for 3 months after
      bioprosthetic aortic valve replacement. We examined neurologic events within 90
      days of bioprosthetic aortic valve replacement at our institution. METHODS:
      Between 1993 and 2000, 1151 patients underwent bioprosthetic aortic valve
      replacement with (641) or without (510) associated coronary artery bypass. By
      surgeon preference, 624 had early postoperative anticoagulation (AC+) and 527 did
      not (AC-). In the AC- group, 410 patients (78%) received antiplatelet therapy.
      Groups were similar with respect to gender (female, 36% AC+ vs 40% AC-, P = .21),
      hypertension (64% AC+ vs 61%, P = .27), and prior stroke (7.6% AC+ vs 8.5% AC-, P
      = .54). The AC+ group was slightly younger than the AC- group (median, 76 years
      vs 78 years, P = .006). RESULTS: Operative mortality was 4.1% with 43 (3.7%)
      cerebrovascular events within 90 days. Excluding 18 deficits apparent upon
      emergence from anesthesia, we found that postoperative cerebrovascular accident
      occurred in 2.4% of AC+ and 1.9% AC- patients. By multivariable analysis, the
      only predictor of operative mortality was hypertension ( P < .0001).
      Postoperative cerebrovascular accident was unrelated to warfarin use ( P = .32).
      The incidence of mediastinal bleeding requiring reexploration was similar (5.0%
      vs 7.4%), as were other bleeding complications in the first 90 days (1.1% vs
      0.8%). No variables were predictive of bleeding by multivariate analysis.
      CONCLUSIONS: Although these data do not address the role of antiplatelet agents,
      early anticoagulation with warfarin after bioprosthetic aortic valve replacement
      did not appear to protect against neurologic events.

PMID- 15867777
TI  - Impact of preoperative and postoperative atrial fibrillation on outcome after
      mitral valvuloplasty for nonischemic mitral regurgitation.
AB  - OBJECTIVE: We sought to determine the impact of preoperative or postoperative
      atrial fibrillation on survival, stroke, and cardiac function after mitral
      valvuloplasty for mitral regurgitation. METHODS: Between 1991 and 2003, 1026
      patients with nonischemic/noncardiomyopathy mitral valve regurgitation underwent
      mitral valve plasty in 3 centers; 663 patients remained in sinus rhythm (group
      A), and 363 patients had atrial fibrillation or flutter preoperatively (group B)
      with concomitant maze procedures (group BM, n = 163) or without maze procedures
      (group BN, n = 200). RESULTS: Eight-year freedom from cardiovascular-related
      death was better in group A (99.3%) than group B (BM: 96.9%, BN: 81.6%) ( P <
      .001) and also better in group BM than group BN ( P = .007). The adjusted hazard
      ratio of group B versus group A for preoperative differences was 5.1 (95%
      confidence interval: 1.8-14.8). Eight-year freedom from stroke was better in
      group A (99.2%) than group B (BM: 98.2%, BN: 82.6%) ( P < .001) and also better
      in group BM than group BN ( P < .001). Patients with preoperative atrial
      fibrillation had larger left atria and left ventricular systolic dimensions. The
      adjunct maze procedure improved left ventricular systolic dimensions over mitral
      repair alone (group A vs B: P = .359; group BM vs BN: P = .001). CONCLUSION:
      Preoperative permanent/persistent atrial fibrillation was associated with a
      dilated left atrium and reduced left ventricular function in patients with mitral
      regurgitation. Including the maze procedure with mitral repair improved survival,
      late cardiac function, and freedom from late stroke.

PMID- 15867778
TI  - Which biologic valve should we select for the 45- to 65-year-old age group
      requiring aortic valve replacement?
AB  - OBJECTIVE: The diversity of biologic valves available to replace the aortic valve
      renders selection difficult for the 45- to 65-year-old patient. To evaluate and
      compare the results of biologic valves in the 45- to 65-year-old patient, we
      reviewed our experience (1991-2004). METHODS: Three hundred thirty-two patients
      between 45 and 65 years old with isolated aortic valve disease had a biologic
      valve implanted: Freestyle valve in 140 patients, a homograft in 54 patients, a
      stented Mosaic or Perimount valve (stented xenograft) in 62 patients, and a Ross
      procedure in 76 patients. RESULTS: Perioperative mortality was comparable for all
      groups (Freestyle, 2.1%; homograft, 3.7%; stented xenograft, 3.2%; Ross
      procedure, 1.3%; P = .8). Echocardiographically determined valve performance at
      discharge was significantly enhanced in the Ross procedure and homograft groups
      (indexed effective orifice area: Freestyle, 0.9 +/- 0.3 cm 2 /m 2 ; homograft,
      1.3 +/- 0.3 cm 2 /m 2 ; stented xenograft, 0.8 +/- 0.2 cm 2 /m 2 ; Ross
      procedure, 1.4 +/- 0.4; P < .0001; mean gradient: Freestyle, 12.0 +/- 6.6 mm Hg;
      homograft, 7.4 +/- 4.0 mm Hg; stented xenograft, 15.4 +/- 5.4 mm Hg; Ross
      procedure, 4.6 +/- 3.2 mm Hg; P < .0001). For all yearly follow-up, freedom from
      New York Heart Association class III or IV was comparable and greater than 95%
      for all groups. At 7 years, cardiac survival (homograft, 96.3% +/- 3.7%; Ross
      procedure, 90.6% +/- 6.3%; stented xenograft, 86.0% +/- 10.3%; Freestyle, 89.2%
      +/- 10.8%; P = .7) and freedom from reoperation (Ross procedure, 98.5% +/- 1.4%;
      homograft, 90.6% +/- 5.7%; Freestyle, 88.0% +/- 4.9%; stented xenograft, 90.0% +/
      8.0%; P = .4) were comparable. Freedoms from significant bleeding events, valve
      related neurologic events, or endocarditis were comparable and greater than 95%
      for all groups. CONCLUSION: Type of aortic biologic valve for the 45- to 65-year
      old patient does not affect midterm survival or valve-related morbidity. Thus the
      choice of biologic valve for the 45- to 65-year-old patient should be dictated by
      patient-surgeon preference, ease of implantation, and reoperation until longer
      comparative studies are available.

PMID- 15867779
TI  - Acute traumatic aortic rupture: a comparison of surgical and stent-graft repair.
AB  - OBJECTIVE: The study's objective was to comparatively evaluate surgery and stent
      graft repair of acute or subacute traumatic aortic rupture. METHODS: A total of
      76 patients (14-76 years old; mean, 37 years; male/female ratio, 63/11) with a
      traumatic aortic injury were admitted to our hospital between 1981 and 2003. Six
      patients died within 1 to 9 days of another associated severe traumatic lesion.
      The 70 remaining patients were divided according to the type of rupture repair.
      In group 1, 35 patients were treated surgically: 28 with immediate repair and 7
      with delayed repair (average time interval 66 days, 5-257 days). In group 2, 29
      patients were treated with stent grafting of the aortic isthmus. In group 3, 6
      patients with minor aortic lesions were treated medically with a close follow-up.
      RESULTS: In the 28 patients treated surgically in the emergency department, the
      mortality and paraplegia rates were 21% and 7%, respectively. No death or
      paraplegia was observed in the group with delayed surgical repair. With stent
      grafting, complete exclusion of the pseudoaneurysmal sac was observed in all
      patients. Except for 1 iliac rupture treated during the same procedure, there was
      no major morbidity or mortality during the mean follow-up of 46 months (13-90
      months). No major complication was observed in group 3. CONCLUSIONS: In stable
      rupture of the aorta, initial conservative treatment is safe and allows
      management of the major associated lesions. Stent grafting of the aortic isthmus
      is a valuable therapeutic alternative to surgical repair, especially in patients
      considered high risk for conventional thoracotomy.

PMID- 15867780
TI  - Exercise hemodynamics of bovine versus porcine bioprostheses: a prospective
      randomized comparison of the mosaic and perimount aortic valves.
AB  - OBJECTIVE: This prospective randomized study compares a porcine with a bovine
      bioprosthesis in the aortic position with regard to hemodynamic performance
      during exercise. METHODS: Between August of 2000 and December of 2002, 136
      patients underwent aortic valve replacement with the porcine Medtronic Mosaic (n
      = 66) or the bovine Carpentier-Edwards Perimount (n = 70) bioprosthesis.
      Transthoracic echocardiography was performed to assess hemodynamic and
      dimensional data preoperatively and 10 months postoperatively; the latter follow
      up included stress echocardiography with treadmill exercise. RESULTS: At rest and
      during exercise (25 and 50 W), there was a significant difference in mean
      pressure gradient between the bovine and the porcine valves with labeled sizes 21
      and 23, with superiority of the Perimount prosthesis. There was no difference in
      effective orifice area and incidence of patient-prosthesis mismatch among all
      sizes. The left ventricular mass index decreased significantly within 10 months
      postoperatively in the size 23 bovine group and the size 25 porcine group.
      CONCLUSIONS: Our data show a significant superiority of pressure gradients for
      the bovine bioprosthesis, especially with small valve sizes, when compared with
      the porcine device, which is more distinctive during exercise.

PMID- 15867781
TI  - The tissue-engineered vascular graft using bone marrow without culture.
AB  - OBJECTIVE: To overcome the shortcomings of current vascular grafts, tissue
      engineering methods have been applied to cardiovascular regions. We previously
      reported the creation of a tissue-engineered vascular graft by using vascular
      mixed cells. However, the cost and manpower for harvesting and culturing the
      cells was too burdensome. To overcome these drawbacks, we have developed a new
      method for creating a tissue-engineered vascular graft by using bone marrow
      cells, which can be obtained easily and used immediately, without cell culture.
      METHODS: Biodegradable polymers seeded with different types of cells (group V,
      cultured venous cells; group B, bone marrow cells without culture; and group C,
      non-cell-seeded graft [as control]) were implanted into the inferior venae cavae
      of dogs. The grafts were explanted at 4 weeks and assessed histologically and
      biochemically. RESULTS: In the histologic examination, a regular layer of Masson
      staining collagen fiber and a layer of factor VII-stained endothelial and ant
      alpha-smooth muscle cell antigen-immunoreactive cells stained in groups V and B
      like native vascular tissue, whereas no such stained regular lining was detected
      in group C. A 4-hydroxyproline assay in group C showed significantly lower levels
      than in groups V and B or native tissue ( P < .05). The DNA content of the tissue
      engineered vascular graft tended to be higher in group C than in groups V and B
      or in native tissue. CONCLUSIONS: In the creation of tissue-engineered vascular
      grafts, the method of using bone marrow cells seems to be useful and superior to
      that of using vascular cells because bone marrow cells can be used directly,
      without culture.

PMID- 15867782
TI  - Improvement of myocardial contractility in a porcine model of chronic ischemia
      using a combined transmyocardial revascularization and gene therapy approach.
AB  - OBJECTIVES: The purpose of this study was to investigate whether a novel
      fibroblast growth factor-2 gene formulation, providing a localized and sustained
      availability of the adenoviral vector from a collagen-based matrix, in
      combination with CO 2 transmyocardial laser revascularization would lead to an
      enhanced angiogenic response and improved myocardial function. METHODS:
      Fibroblast growth factor-2 gene was delivered by means of an adenoviral vector
      (adenoviral fibroblast growth factor-2) formulated in a collagen-based matrix.
      The ischemic areas of 33 animals were then treated. Group 1 was treated with CO 2
      transmyocardial laser revascularization; group 2 was treated with intramyocardial
      injections of adenoviral fibroblast growth factor-2 in a collagen-based matrix;
      group 3 had a combination treatment of matrix adenoviral fibroblast growth factor
      2 and CO 2 transmyocardial laser revascularization; and group 4 received
      injections with saline-formulated adenoviral fibroblast growth factor-2. Baseline
      left ventricular function was assessed by echocardiography and cine magnetic
      resonance imaging. Studies were repeated 6 weeks after treatment. Vascular
      development was assessed using anti-alpha-actin immunohistochemistry. RESULTS:
      Matrix adenoviral fibroblast growth factor-2 + transmyocardial laser
      revascularization-treated areas had a 105% increase in arteriolar development
      versus either treatment alone ( P < .05) and a 390% increase compared with saline
      formulated adenoviral fibroblast growth factor-2 treatment alone ( P < .05).
      Contractility was significantly improved in matrix adenoviral fibroblast growth
      factor-2 + transmyocardial laser revascularization-treated areas as measured by
      myocardial wall thickening. This functional improvement was confirmed by cine
      magnetic resonance imaging, in which a 90% increase in the contractility of the
      treated segments was demonstrated after matrix adenoviral fibroblast growth
      factor-2 + transmyocardial laser revascularation. The other treatments provided
      significantly less restoration of myocardial function. CONCLUSIONS: The increase
      in angiogenesis as a result of matrix adenoviral fibroblast growth factor-2 gene
      therapy in combination with CO 2 transmyocardial laser revascularization is
      greater than that seen in either therapy alone. A concomitant improvement in
      myocardial function was seen as a result of this angiogenic response.

PMID- 15867783
TI  - Detection of construction errors in ex vivo coronary artery anastomoses by 13-MHz
      epicardial ultrasonography.
AB  - OBJECTIVE: Intraoperative detection of suboptimal coronary anastomoses allows
      revision before chest closure. We evaluated an epicardial 13-MHz ultrasound
      minitransducer as a means to detect three different coronary anastomosis
      construction errors. METHODS: In total, 120 internal thoracic artery-to-coronary
      artery anastomoses were constructed correctly (n = 60) or incorrectly (n = 60)
      with one technical error: suture crossover, purse-string or deep toe stitch (n =
      20 each). Anastomoses were performed on ex vivo pressure-perfused porcine (96
      anastomoses) and human hearts (24 anastomoses). Two blinded observers scanned and
      scored the anastomoses with epicardial ultrasonography. In 24 human and 24
      porcine anastomoses, angiograms were made of 24 correct and 24 incorrect
      anastomoses and scored by two other blinded observers. Angioscopy and cast
      injection served as a reference. RESULTS: Overall, 119 of 120 anastomoses were
      accurately scored as correct or incorrect within a median of 67 seconds (8-381
      seconds) by both observers (sensitivity 0.98, specificity 1.00, kappa 1.00 (1.00,
      1.00, and 1.00 in angiography subset, respectively). One deep toe stitch that
      induced outflow corner stenosis was spotted by both observers but regarded as
      insignificant and thus inaccurately scored as correct. In 5 anastomoses,
      unintended irregularities were detected. By angiography, anastomoses were
      accurately scored with a sensitivity of 0.75 and a specificity of 0.81 ( P < .001
      vs ultrasonography) and kappa of 0.54. Angioscopy and cast confirmed
      ultrasonographic findings and did not reveal irregularities other than detected
      by ultrasonography. CONCLUSION: Ex vivo epicardial 13-MHz ultrasonography allowed
      rapid and accurate evaluation of coronary anastomoses and detected technical
      construction errors with higher sensitivity and specificity than angiography.

PMID- 15867784
TI  - Cost-utility analysis of salvage cardiac extracorporeal membrane oxygenation in
      children.
AB  - BACKGROUND: Indications for extracorporeal membrane oxygenation therapy have
      expanded to include cardiopulmonary arrest and support after congenital heart
      surgery. Data from a national registry have reported that cardiac patients have
      the poorest survival of all extracorporeal membrane oxygenation recipients.
      Concerns have been raised about the appropriateness of such an aggressive
      strategy, especially in light of the high costs and potential for long-term
      neurologic disability. We reviewed our experience with salvage cardiac
      extracorporeal membrane oxygenation to determine the cost-utility, which accounts
      for both costs and quality of life. METHODS: Medical records of patients with
      congenital heart disease receiving salvage cardiac extracorporeal membrane
      oxygenation between January 2000 and May 2004 were reviewed. Charges for all
      medical care after the institution of extracorporeal membrane oxygenation were
      determined and converted to costs by published standards. The quality-of-life
      status of survivors was determined with the Health Utilities Index Mark II.
      RESULTS: Salvage cardiac extracorporeal membrane oxygenation was instituted in 32
      patients (18 for cardiopulmonary arrest and 14 for cardiac failure after heart
      surgery) at a median age of 2.0 months (range, 4 days to 5.1 years). Congenital
      heart disease was present in 27 (84%). The mean duration of extracorporeal
      membrane oxygenation support was 5.1 +/- 4.1 days. Survival to hospital discharge
      was 50%, including 1 patient bridged to heart transplantation. Survival to 1 year
      was 47%. The mean score of the Health Utilities Index for the survivors was 0.75
      +/- 0.19 (range, 0.41-1.0). The median cost for hospital stay after the
      institution of extracorporeal membrane oxygenation was USD 156,324 per patient.
      The calculated cost-utility for salvage extracorporeal membrane oxygenation in
      this population was USD 24,386 per quality-adjusted life-year saved, which would
      be considered within the range of accepted cost-efficacy (< USD 50,000 per
      quality-adjusted life-year saved). CONCLUSIONS: Salvage cardiac extracorporeal
      membrane oxygenation results in reasonable survival and is justified on a cost
      utility basis.

PMID- 15867785
TI  - Late neurodevelopmental outcome after repair of total anomalous pulmonary venous
      connection.
AB  - Objective We sought to define the neurodevelopmental status of school-aged
      survivors of total anomalous pulmonary venous connection repaired during infancy.
      Methods All school-aged survivors of total anomalous pulmonary venous connection
      repair performed at a single institution were eligible. Thirty children returned
      for neurologic examination and neurodevelopmental testing. Results The median age
      at total anomalous pulmonary venous connection repair was 16 days (range, 1-141
      days), and age at testing was 11 years (range, 6-19 years). Pulmonary venous
      return was supracardiac in 14 patients, infracardiac in 12 patients, cardiac in 3
      patients, and mixed in 1 patient. Preoperative obstructed total anomalous
      pulmonary venous connection was present in 6 patients. Circulatory arrest was
      used in all repairs, with a median duration of 35 minutes (range, 17-55 minutes).
      At follow-up, microcephaly (head circumference <5%) was present in 28%.
      Neuromuscular examination was suspect or abnormal in 27%. Mean Full-scale IQ
      (95.3 +/- 18.5) and Verbal IQ (98.6 +/- 20.2) were not different from population
      norms, but Performance IQ (92.3 +/- 16.9) was significantly lower than population
      norms ( P = .02). Fine motor skills and visual-motor coordination were
      significantly impaired ( P < .01 for Grooved Pegboard and Test of Visual-Motor
      Integration). Patients with total anomalous pulmonary venous connection also had
      difficulty with tests of attention (Test of Everyday Attention for Children, P <
      .01), but results of tests of memory function were not significantly different
      from population norms. Conclusions School-aged survivors of infant total
      anomalous pulmonary venous connection repair exhibit a significant incidence of
      neurodevelopmental difficulties. Fine motor function, visual-motor integration,
      and attention are the most commonly affected domains. Evaluation of these
      children is indicated to identify those who are at risk for learning disabilities
      and who could benefit from early intervention.

PMID- 15867786
TI  - Soluble alpha2-macroglobulin receptor is increased in endotracheal aspirates from
      infants and children after cardiopulmonary bypass.
AB  - OBJECTIVE: Cytokine dysregulation contributes to the systemic inflammatory
      response after cardiopulmonary bypass. Clearance of cytokine binding proteins may
      be important in the resolution of inflammation. Our aim was to determine whether
      the cytokine binding protein alpha 2 -macroglobulin and its soluble receptor were
      upregulated in endotracheal aspirates from infants and children undergoing
      cardiopulmonary bypass. METHODS: Seventy tracheal aspirates were collected before
      and after cardiopulmonary bypass from 35 infants and children undergoing surgical
      correction of congenital heart defects. alpha 2 -Macroglobulin and the soluble
      alpha 2 -macroglobulin receptor were identified by Western blot. With the use of
      multi-analyte cytokine profiling, pro-inflammatory and anti-inflammatory
      cytokines were quantified, normalized to total protein, and expressed as ratios.
      Paired t tests and Wilcoxon signed-rank tests were performed between prebypass
      and postbypass samples. Correlations were examined among alpha 2 -macroglobulin,
      soluble alpha 2 -macroglobulin receptor, cytokine ratios, and the clinical
      variables of cardiopulmonary bypass, aortic crossclamp, and circulatory arrest
      times. RESULTS: alpha 2 -Macroglobulin increased by 50% (mean densitometry
      increase 82,683 +/- 184,594, P = .012), and soluble alpha 2 -macroglobulin
      receptor increased by 17% (mean densitometry increase 506,148 +/- 687,037, P =
      .0001) after cardiopulmonary bypass. The ratio of interleukin-8/interleukin-4
      increased by 136% ( P = .0001), and interleukin-8/interleukin-10 increased by
      102% ( P = .001). The increase in soluble alpha 2 -macroglobulin receptor was
      positively correlated with the ratios of interleukin-8/interleukin-4 and
      interleukin-8/interleukin-10. There were no statistically significant positive
      correlations between the increase in alpha 2 -macroglobulin or soluble alpha 2 
      macroglobulin receptor and measured clinical variables. CONCLUSIONS: We report
      for the first time the upregulation of alpha 2 -macroglobulin and soluble alpha 2
      -macroglobulin receptor in tracheal aspirates after cardiopulmonary bypass in
      infants and children. Soluble alpha 2 -macroglobulin receptor correlates with
      increased alpha 2 -macroglobulin and a disproportionate increase in pro
      inflammatory to anti-inflammatory cytokine ratios.

PMID- 15867787
TI  - Dysfunction of atrial and B-type natriuretic peptides in congenital
      univentricular defects.
AB  - OBJECTIVE: To examine whether children with univentricular defects have intrinsic
      dysfunction in the natriuretic peptide system. METHODS: We compared plasma levels
      of the fluid-regulating hormone vasopressin (antidiuretic hormone), aldosterone,
      atrial natriuretic peptide, and brain natriuretic peptide in children with
      congenital univentricular and biventricular defects. We enrolled 27 patients with
      univentricular defects and 27 patients with biventricular cardiac defects.
      Children who underwent Fontan and Glenn procedures were considered as patients
      with univentricular cardiac defects; children who underwent repair of tetralogy
      of Fallot or subaortic stenosis were considered as controls with biventricular
      defects. RESULTS: Preoperative plasma atrial natriuretic peptide, brain
      natriuretic peptide, antidiuretic hormone, and aldosterone were comparable in
      both groups. Although plasma cyclic guanosine monophosphate levels were
      comparable between groups, there was a significant correlation between molar
      concentrations of plasma cyclic guanosine monophosphate and plasma atrial
      natriuretic peptide ( r = 0.42) and brain natriuretic peptide ( r = 0.44) in the
      biventricular group, but not in the univentricular group ( r = 0.19 for atrial
      natriuretic peptide; r = 0.13 for brain natriuretic peptide). All patients had a
      significant postoperative increase in plasma antidiuretic hormone. A significant
      postoperative increase in plasma brain natriuretic peptide was found in the
      patients with biventricular, but not univentricular, defects. In contrast, a
      significant increase in plasma aldosterone was observed only in the patients with
      univentricular defects. CONCLUSIONS: There were distinct differences between
      univentricular and biventricular groups in their perioperative plasma fluid
      regulating hormone responses. Specifically, patients with univentricular defects
      may have abnormal natriuretic peptide secretion and function. The natriuretic
      dysfunction may be on the basis of hypoplastic ventricular development.

PMID- 15867788
TI  - Preoperative and postoperative evaluation of airways compression in pediatric
      patients with 3-dimensional multislice computed tomographic scanning: effect on
      surgical management.
AB  - OBJECTIVES: Surgical management of airway compression of vascular origin requires
      an accurate analysis of anatomy and various mechanisms of compression. This study
      assessed the usefulness of 3-dimensional computed tomographic scanning in the
      preoperative and postoperative evaluation of airways compression in a pediatric
      population. METHODS: Thirty-seven consecutive patients (median age, 4 months)
      were examined with multislice 3-dimensional computed tomographic scanning: 18
      patients before surgical treatment of anomalies of vascular rings, 2 patients
      because of respiratory symptoms after repair of esophageal atresia, and 17
      patients because of persisting respiratory symptoms or prolonged mechanical
      ventilation after cardiac surgery for congenital heart disease. RESULTS: The
      procedure was successful, with high-quality diagnostic imaging obtained in all
      cases without any complications. The anatomy and relationship between the
      vascular arches and airways was analyzed in all referred patients with vascular
      arch anomalies confirmed on the basis of the surgical findings, and this helped
      the surgeon to plan the procedure and choose the best approach. After cardiac
      surgery, the airway and vascular structures involved and the mechanism of
      compression were specified in all but one case, and the 3-dimensional computed
      tomographic scan serves as an important tool for deciding whether to perform
      reoperation on patients requiring prolonged mechanical ventilation. CONCLUSION:
      Three-dimensional computed tomographic scanning is a safe, fast, and noninvasive
      method useful for accurately analyzing the mechanisms of airway compression of
      vascular origin and thus possible improving the surgical management of pediatric
      patients.

PMID- 15867789
TI  - Noncultured cell transplantation in an ovine model of right ventricular
      preparation.
AB  - OBJECTIVE: Beyond the first 2 months of life, pulmonary artery banding is
      warranted before two-stage arterial switch operation. The aim of this study was
      to explore whether myogenic cell transplantation could contribute to right
      ventricular function during pulmonary artery constriction in an ovine model.
      METHODS: Sixteen rams were assigned to one of the following groups: group 1,
      simple pulmonary artery banding (n = 5); group 2, pulmonary artery banding and
      cell implantation in the right ventricle (n = 7); and group 3, pulmonary artery
      banding and placebo injection in the right ventricle (n = 4). Hemodynamic
      assessment with pressure-volume loops was performed on days 0 and 60. The
      pulmonary artery banding and the injections were achieved through a left fourth
      intercostal thoracotomy. Autologous myogenic cell implantation was carried out
      with a noncultured cell preparation, as previously described by our group.
      Implanted sites were processed with monoclonal antibodies to a fast skeletal
      specific isoform of myosin heavy chain (MY32). RESULTS: Skeletal myosin heavy
      chain expression was detected at 2 months after noncultured cell implantation in
      all grafted animals. Right ventricular training resulted in statistically
      significant increased signs of contractility in all three groups. There was no
      observed difference, however, between the cell therapy group and the other two
      groups with respect to signs of cardiac function. CONCLUSION: Successful
      engraftment of noncultured cells into right ventricular myocardium did not
      translate into a functional benefit that we could demonstrate in our ovine model.
      Cellular therapy thus is probably not useful to strengthen a left ventricle being
      retrained through pulmonary artery banding before arterial switch operation.
      However, cell transplantation may affect the outcome of right ventricular failure
      long term after atrial switch operation. Although preliminary, this investigation
      paves the way for further research into cellular cardiomyoplasty, right
      ventricular failure, and congenital heart disease.

PMID- 15867790
TI  - Cardioprotective stress response in the human fetal heart.
AB  - OBJECTIVE: We propose that the fetal heart is highly resilient to hypoxic stress.
      Our objective was to elucidate the human fetal gene expression profile in
      response to simulated ischemia and reperfusion to identify molecular targets that
      account for the innate cardioprotection exhibited by the fetal phenotype.
      METHODS: Primary cultures of human fetal cardiac myocytes (gestational age, 15-20
      weeks) were exposed to simulated ischemia and reperfusion in vitro by using a
      simulated ischemic buffer under anoxic conditions. Total RNA from treated and
      baseline cells were isolated, reverse transcribed, and labeled with Cy3 or Cy5
      and hybridized to a human cDNA microarray for expression analysis. This analysis
      revealed a highly significant (false discovery rate, <3%) suppression of
      interleukin 6 transcript levels during the reperfusion phase confirmed by means
      of quantitative polymerase chain reaction (0.25 +/- 0.11-fold). Interleukin 6
      signaling during ischemia and reperfusion was assessed at the protein expression
      level by means of Western measurements of interleukin 6 receptor, the signaling
      subunit of the interleukin 6 receptor complex (gp130), and signal transducer of
      activated transcription 3. Posttranslational changes in the protein kinase B
      signaling pathway were determined on the basis of the phosphorylation status of
      protein kinase B, mitogen-activated protein kinase, and glycogen synthase kinase
      3beta. The effect of suppression of a prohypertrophic kinase, integrin-linked
      kinase, with short-interfering RNA was determined in an ischemia and reperfusion
      stressed neonatal rat cardiac myocyte model. Endogenous secretion of interleukin
      6 protein in culture supernatants was measured by enzyme-linked immunosorbent
      assay. RESULTS: Human fetal cardiac myocytes exhibited a significantly lower rate
      of apoptosis induction during ischemia and reperfusion and after exposure to
      staurosporine and recombinant interleukin 6 compared with that observed in
      neonatal rat cardiac myocytes ( P < .05 for all comparisons, analysis of
      variance). Exposure to exogenously added recombinant interleukin 6 increased the
      apoptotic rate in both rat and human fetal cardiac myocytes ( P < .05). Short
      interfering RNA-mediated suppression of integrin-linked kinase, a prohypertrophy
      upstream kinase regulating protein kinase B and glycogen synthase kinase 3beta
      phosphorylation, was cytoprotective against ischemia and reperfusion-induced
      apoptosis in neonatal rat cardiac myocytes ( P < .05). CONCLUSIONS: Human fetal
      cardiac myocytes exhibit a uniquely adaptive transcriptional response to ischemia
      and reperfusion that is associated with an apoptosis-resistant phenotype. The
      stress-inducible fetal cardiac myocyte gene repertoire is a useful platform for
      identification of targets relevant to the mitigation of cardiac ischemic injury
      and highlights a novel avenue involving interleukin 6 modulation for preventing
      the cardiac myocyte injury associated with ischemia and reperfusion.

PMID- 15867791
TI  - Adenosine A2A receptor activation reduces inflammation and preserves pulmonary
      function in an in vivo model of lung transplantation.
AB  - BACKGROUND: Reperfusion injury continues to significantly affect patients
      undergoing lung transplantation. Isolated lung models have demonstrated that
      adenosine A 2A receptor activation preserves function while decreasing
      inflammation. We hypothesized that adenosine A 2A receptor activation by ATL-146e
      during the initial reperfusion period preserves pulmonary function and attenuates
      inflammation in a porcine model of lung transplantation. METHODS: Mature pig
      lungs preserved with Viaspan (Barr Laboratories, Pomona, NY) underwent 6 hours of
      cold ischemia before transplantation and 4 hours of reperfusion. Animals were
      treated with (ATL group, n = 7) and without (IR group, n = 7) ATL-146e (0.05
      microg kg -1 . min -1 ATL-146e administered intravenously for 3 hours). With
      occlusion of the opposite pulmonary artery, the animal was maintained for the
      final 30 minutes on the allograft alone. Recipient lung physiology was monitored
      before tissue evaluation of pulmonary edema (wet-to-dry weight ratio),
      myeloperoxidase assay, and tissue tumor necrosis factor alpha by means of enzyme
      linked immunosorbent assay. RESULTS: When the ATL group was compared with the IR
      group, the ATL group had better partial pressure of carbon dioxide (43.8 +/- 4.1
      vs 68.9 +/- 6.3 mm Hg, P < .01) and partial pressure of oxygen (272.3 +/- 132.7
      vs 100.1 +/- 21.4 mm Hg, P < .01). ATL-146e-treated animals exhibited lower
      pulmonary artery pressures (33.6 +/- 2.1 vs 47.9 +/- 3.5 mm Hg, P < .01) and mean
      airway pressures (16.25 +/- 0.08 vs 16.64 +/- 0.15 mm Hg, P = .04). ATL-146e
      treated lungs had lower wet-to-dry ratios (5.9 +/- 0.39 vs 7.3 +/- 0.38, P <
      .02), lower myeloperoxidase levels (2.9 x 10 -5 +/- 1.2 x 10 -5 vs 1.3 x 10 -4 +/
      4.0 x 10 -5 DeltaOD mg -1 . min -1 , P = .03), and a trend toward decreased lung
      tumor necrosis factor alpha levels (57 +/- 12 vs 96 +/- 15 pg/mL, P = .06). The
      ATL group demonstrated significantly less inflammation on histology. CONCLUSION:
      Adenosine A 2A activation during early reperfusion attenuated lung inflammation
      and preserved pulmonary function in this model of lung transplantation. ATL-146e
      and similar compounds could play a significant role in improving outcomes of
      pulmonary transplantation.

PMID- 15867792
TI  - Bile acid aspiration and the development of bronchiolitis obliterans after lung
      transplantation.
AB  - BACKGROUND: Aspiration of gastroesophageal refluxate may contribute to lung
      transplant bronchiolitis obliterans syndrome (BOS). We investigated bile acids in
      bronchoalveolar lavage fluid (BALF) and studied its role in BOS. MATERIALS AND
      METHODS: Surveillance pulmonary function tests and BALF were evaluated in 120
      lung recipients. BOS-(0p-3) was diagnosed after 6 months' survival. BOS was
      defined as "early" if diagnosed within 12 months after a transplant. BALF was
      assayed for differential cell count, bile acids, and interleukins 8 and 15. Bile
      acids were considered elevated if greater than normal serum levels ( or =8
      micromol/L). RESULTS: Elevated BALF bile acids were measured in 20 (17%) of 120
      patients. BOS was diagnosed in 36 (34%) of 107 patients and judged "early" in 21
      (57%) of 36. Median BALF bile acid values were 1.6 micromol/L (range, 0-32
      micromol/L) in BOS patients and 0.3 micromol/L (range, 0-16 micromol/L) in non
      BOS patients ( P = .002); 2.6 micromol/L (range, 0-32 micromol/L) in early BOS
      patients and 0.8 micromol/L (range, 0-4.6 micromol/L) in late BOS patients, ( P =
      .02). Bile acids correlated with BALF IL-8 and alveolar neutrophilia (r = 0.3, P
      = .0004, and r = 0.3, P = .004, respectively), but not with IL-15. Freedom from
      BOS was significantly shortened in patients with elevated BALF bile acids (Cox
      Mantel test, P = .0001). CONCLUSIONS: Aspiration of duodenogastroesophageal
      refluxate is prevalent after lung transplantation and is associated with the
      development of BOS. Elevated BALF bile acids may promote early BOS development
      via an inflammatory process, possibly mediated by IL-8 and alveolar neutrophilia.

PMID- 15867793
TI  - Donor cause of death and medium-term survival after heart transplantation: a
      United Kingdom national study.
AB  - OBJECTIVE: Donor cause of death may be a risk factor for early mortality after
      heart transplantation, but its effect on medium-term survival is uncertain.
      METHODS: By means of a national prospective database, we investigated the
      influence of donor cause of death on survival to 3 years in 1254 adult recipients
      of cadaveric heart transplantation between July 1995 and June 2002. Donor cause
      of death was categorized a priori as vascular and tumor (group V, n = 739),
      trauma (group T, n = 407), hypoxic (group H, n = 82), and infective causes (group
      I, n = 26). Risk factors for early (30-day), late (30-day to 3-year), and overall
      mortality were identified with Cox regression. RESULTS: Group V donors were more
      likely to be older ( P < .001) and female ( P < .001). There were 297 deaths in
      the 3-year period, and the unadjusted 3-year survivals varied significantly
      (group V 73%, group T 79%, group H 85%, group I 80%, P = .01). Cox analysis
      identified donor age, organ ischemia time, recipient creatinine clearance,
      recipient diagnosis, peripheral vascular disease, ventilation, diabetes, and
      donor-recipient size mismatch as risk factors for early, late, or overall
      mortality ( P < .10). After adjustment for these factors, donor cause of death
      was no longer a significant predictor of recipient death (early death P = .36,
      late death P = .79, overall mortality P = .37). CONCLUSION: We confirmed that
      there is an apparent association between cause of donor death and
      posttransplantation survival, but this was not maintained after adjustment for
      confounding variables. Donor cause of death therefore should not influence donor
      organ acceptance or donor-recipient matching and does not identify marginal
      donors.

PMID- 15867794
TI  - Inhibition of heart transplant injury and graft coronary artery disease after
      prolonged organ ischemia by selective protein kinase C regulators.
AB  - OBJECTIVE: Transplanted hearts subjected to prolonged ischemia develop ischemia
      reperfusion injury and graft coronary artery disease. To determine the effect of
      delta-protein kinase C and -protein kinase C on ischemia-reperfusion injury and
      the resulting graft coronary artery disease induced by prolonged ischemia, we
      used a delta-protein kinase C-selective inhibitor peptide and an -protein kinase
      C-selective activator peptide after 30 or 120 minutes of ischemia. METHODS:
      Hearts of piebald viral glaxo (PVG) rats were heterotopically transplanted into
      allogeneic August Copenhagen Irish (ACI) rats. After cardioplegic arrest of the
      donor heart, -protein kinase C activator was injected antegrade into the coronary
      arteries. Hearts were procured and bathed in -protein kinase C activator, and
      before reperfusion, delta-protein kinase C inhibitor was injected into the
      recipient inferior vena cava. Controls were treated with saline. To analyze
      ischemia-reperfusion injury, grafts were procured at 4 hours after
      transplantation and analyzed for superoxide generation; myeloperoxidase activity;
      tumor necrosis factor alpha, interleukin 1beta, and monocyte/macrophage
      chemoattractant protein 1 production; and cardiomyocyte apoptosis by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling and caspase 2, 3, 8,
      and 9 activity. To analyze graft coronary artery disease, another set of animals
      underwent equal ischemic times and treatment strategies and then after 90 days
      were analyzed for graft coronary artery disease indexes. RESULTS: All measures of
      ischemia-reperfusion injury and graft coronary artery disease after 120 minutes
      of ischemia in the saline-treated group were significantly increased relative to
      those observed after 30 minutes of ischemia. It is important to note that all
      ischemia-reperfusion injury parameters and graft coronary artery disease indexes
      decreased significantly in the protein kinase C regulator-treated group in
      comparison to saline-treated controls; additionally, these values were equivalent
      to those in saline-treated controls with 30 minutes of ischemia. CONCLUSIONS:
      Combined treatment with -protein kinase C activator and delta-protein kinase C
      inhibitor reduces ischemia-reperfusion injury and decreases the resulting graft
      coronary artery disease induced by prolonged ischemia.

PMID- 15867795
TI  - Extramedullary plasmacytoma immunoglobulin D (lambda) in the chest wall and the
      subglottic region.

PMID- 15867796
TI  - Bilateral pulmonary artery aneurysm in Behcet syndrome: report of two operative
      cases.

PMID- 15867797
TI  - Long-term remission with surgery for recurrent localized Hodgkin lymphoma.

PMID- 15867798
TI  - Chordal cutting technique through aortotomy: a new approach to treat chronic
      ischemic mitral regurgitation.

PMID- 15867799
TI  - Submitral left ventricular aneurysm: the location of the circumflex coronary
      artery in relation to the aneurysm influences the surgical approach and outcome.

PMID- 15867800
TI  - Sternal resection and reconstruction after renal cell carcinoma metastatic to the
      sternum.

PMID- 15867801
TI  - Unusual impalement injury in a Jehovah's Witness.

PMID- 15867802
TI  - Reimplantation of a left internal thoracic artery during repeat coronary artery
      revascularization: early and midterm results.

PMID- 15867803
TI  - Open-window thoracostomy and microvascular muscle flap for severe intrathoracic
      infection around aortic prosthetic graft.

PMID- 15867804
TI  - Novel knot-tying technique for mitral valve repair.

PMID- 15867805
TI  - How to avoid traction to a pedicled internal thoracic artery graft.

PMID- 15867806
TI  - Closure of ventricular septal defects in the donor heart before transplantation:
      toward expanded acceptance criteria.

PMID- 15867807
TI  - Giant soft tissue liposarcoma of chest wall.

PMID- 15867808
TI  - Cerebral malperfusion in acute type A dissection: direct innominate artery
      cannulation.

PMID- 15867809
TI  - Is there any change in free flow of pedicled left internal thoracic artery
      conduit at varying degrees of clockwise twist up to 360 degrees ?

PMID- 15867810
TI  - Distinguishing solid from gaseous emboli during cardiac surgery.

PMID- 15867811
TI  - The answer is an intra-aortic balloon pump.

PMID- 15867812
TI  - Difficulty of early diagnosis in patients with solitary pulmonary nodule.

PMID- 15867813
TI  - Why clopidogrel failed to inhibit platelet function early after coronary artery
      bypass surgery: to load or not to load, and is it a question of resistance?

PMID- 15867814
TI  - Aortic dissection and ankylosing spondylitis in hypocystinemia.

PMID- 15867815
TI  - Catamenial pneumothorax: some commentaries.

PMID- 15867816
TI  - Randomized prospective trial for blood transfusion during adult cardiopulmonary
      bypass surgery.

PMID- 15867817
TI  - Hematocrit trial.

PMID- 15867818
TI  - Extrapleural pneumonectomy for malignant mesothelioma: should pericardium be
      resected routinely?

PMID- 15867819
TI  - Carbodissection of the internal thoracic artery.

PMID- 15867820
TI  - Technique for microsphere injection.

PMID- 15867821
TI  - Early ischemic preconditioning provides transient protection.

PMID- 15867822
TI  - Chemotherapy in non-small cell lung cancer: an update of an individual patient
      data-based meta-analysis.

PMID- 15867823
TI  - Single-stage repair of extensive thoracic aortic aneurysms.

PMID- 15867824
TI  - Total aortic arch replacement and limited circulatory arrest of the brain.

PMID- 15867825
TI  - Bioengineered airway tissue.

PMID- 15867826
TI  - I remember when a mouse had four legs.

PMID- 15867827
TI  - Charity begins at home.

PMID- 15867828
TI  - Bipolar disorders in children and adolescents.
AB  - In the past decade, 7 million children in the United States had a mental health
      problem, with higher rates of medication use, primary care visits, and specialty
      care visits than children without such problems. Children with bipolar disorders
      can present diagnostic and referral dilemmas for the primary care pediatric nurse
      practitioner, and frequently these children take multiple medications that
      interact with commonly used antibiotics, over-the-counter medications, and
      contraceptives. Diagnostic criteria for mania are controversial and coexisting
      attention deficit/hyperactivity disorder, conduct disorder, and anxiety disorders
      can complicate the diagnosis and treatment. The primary care pediatric nurse
      practitioner role includes referral, co-management, and advocacy for this
      vulnerable population.

PMID- 15867829
TI  - Are there universal parenting concepts among culturally diverse families in an
      inner-city pediatric clinic?
AB  - INTRODUCTION: Cultural competence is necessary in providing care to culturally
      diverse families. Numerous studies have emphasized similarities and differences
      between predetermined cultural groups, yet few have studied groups across
      cultures. This project aimed to investigate parenting concepts, which in this
      context pertains to philosophy of parenting and child care practices across
      cultures. METHOD: Using a grounded theory approach, ethnographic interviews of 46
      families representing 27 countries were taped, transcribed, and analyzed.
      RESULTS: Similarities in parenting concepts were found among families. Teaching
      values and respect and the need for strict discipline were important. A sense of
      community, family, and spirituality/religion was strong. Television was viewed as
      educational and parents anticipated opportunities for jobs and higher education
      for their children. Parents were more inclined to use medical treatments than
      home remedies for acute illnesses, which may have been linked to the finding that
      their providers had a strong influence. Parents feared children playing alone
      outdoors; distrusted nonfamily babysitters; and felt conflicted between a desire
      for cultural preservation versus assimilation. DISCUSSION: Universal concepts in
      parenting philosophies and practices exist among culturally diverse families.
      Providers may approach anticipatory guidance by addressing global parental
      concerns that transcend culture in order to relieve time constraints and the
      overwhelming task of being knowledgeable about all cultures.

PMID- 15867830
TI  - The readability of American Academy of Pediatrics patient education brochures.
AB  - INTRODUCTION: The purpose of this study was to evaluate the readability of
      American Academy of Pediatrics (AAP) patient education brochures. METHOD: Seventy
      four brochures were analyzed using two readability formulas. RESULTS: Mean
      readability for all 74 brochures was grade 7.94 using the Flesch-Kincaid formula,
      and grade 10.1 with SMOG formula (P = .001). Using the SMOG formula, no brochures
      were of acceptably low (< or =8th grade) readability levels (range 8.3 to 12.7).
      Using the Flesch-Kincaid formula, 41 of the 74 had acceptable readability levels
      (< or =8th grade). The SMOG formula routinely assessed brochures 2 to 3 grade
      levels higher than did the Flesch-Kincaid formula. DISCUSSION: Some AAP patient
      education brochures have acceptably low levels of readability, but at least half
      are written at higher than acceptable readability levels for the general public.
      This study also demonstrated statistically significant variability between the
      two different readability formulas; had only the SMOG formula been used, all of
      the brochures would have had unacceptably high readability levels. Readability is
      an essential concept for patient education materials. Professional associations
      that develop and market patient education materials should test for readability
      and publish those readability levels on each piece of patient education so health
      care providers will know if the materials are appropriate for their patients.

PMID- 15867831
TI  - Asthma in the pediatric sickle cell patient with acute chest syndrome.
AB  - INTRODUCTION: Acute chest syndrome (ACS) is a potential life-threatening
      complication of sickle cell disease (SCD). The purpose of this study was to
      identify the frequency of asthma in children with SCD who were diagnosed with
      ACS. The objective was to determine if an increased frequency of asthma exists in
      children with SCD and ACS. METHOD: A retrospective descriptive chart review
      covering the period from June 1997 to June 2002 was conducted on 60 children
      ranging in age from 1.5 years to 17 years who had SCD and ACS. Cross-tabs
      analysis and student t tests were used to determine the significance of the
      occurrence of asthma in children in whom ACS developed. RESULTS: Of the 60
      eligible children with SCD, 53% (32/60) had asthma and/or abnormal pulmonary
      function tests prior to the development of ACS. DISCUSSION: This is the first
      study to report a slight increase in the frequency of asthma prior to the initial
      ACS in children with SCD. The small convenience sample size from one center may
      have been a limitation in this study to detect significant differences between
      the variables.

PMID- 15867832
TI  - A practitioner-based asthma intervention program with African American inner-city
      school children.
AB  - INTRODUCTION: Asthma is the most prevalent chronic illness, affecting more than 7
      million children younger than 17 years. Asthma has become a leading public health
      concern because of the dramatic rise in the incidence of this disease during the
      past 15 years, particularly in minority populations. This study tested a two-part
      intervention on selected psychosocial and health outcomes of 8- to 13-year-old
      inner city minority students with asthma. METHOD: The intervention consisted of
      participation in an asthma education program (Open Airways) followed by 5 monthly
      visits with a nurse practitioner. The total sample of 52 children was composed of
      28 children in the treatment group who received the intervention and 24 children
      who served as a control group. RESULTS: Students in the treatment group scored
      significantly higher than the control group over time on measures of asthma
      knowledge, asthma self-efficacy, general self-care practices, and asthma self
      care practices. No significant differences were found between the two groups on
      health outcomes. DISCUSSION: A school-based intervention program can improve
      psychosocial outcomes for inner-city minority children with asthma.
      Recommendations for future research and clinical practice are discussed.

PMID- 15867833
TI  - Evaluation and management of hypertension in children and adolescents (part one):
      diagnosis.

PMID- 15867834
TI  - A wheezing toddler.

PMID- 15867835
TI  - Helping preschoolers become healthy eaters.

PMID- 15867836
TI  - Critiquing research for use in practice.

PMID- 15867837
TI  - Danger in the toy box.

PMID- 15867841
TI  - The epidemiology of obesity and asthma.
AB  - The prevalences of asthma and obesity have increased substantially in recent
      decades in many countries, leading to speculation that obese persons might be at
      increased risk of asthma development. In adults cross-sectional, case-control,
      prospective, and weight-loss studies are in the aggregate consistent with a role
      for obesity in the pathogenesis of asthma. In children 3 of 4 prospective studies
      also show a significant association between excess weight and asthma incidence.
      Because of the methodologic shortcomings of many studies, these findings are
      inconclusive, however. Population surveys do suggest that persons with asthma are
      disproportionately obese compared with persons who have never had asthma. Weight
      loss studies on the basis of behavioral change and bariatric studies have shown
      substantial improvements in the clinical status of many obese patients with
      asthma who lost weight. Clarifying the nature of the relationship between obesity
      and asthma incidence and the role of weight management among patients with asthma
      are both critical areas with important ramifications for the prevention and
      treatment of asthma.

PMID- 15867843
TI  - Adipose tissue, adipokines, and inflammation.
AB  - White adipose tissue is no longer considered an inert tissue mainly devoted to
      energy storage but is emerging as an active participant in regulating physiologic
      and pathologic processes, including immunity and inflammation. Macrophages are
      components of adipose tissue and actively participate in its activities.
      Furthermore, cross-talk between lymphocytes and adipocytes can lead to immune
      regulation. Adipose tissue produces and releases a variety of proinflammatory and
      anti-inflammatory factors, including the adipokines leptin, adiponectin,
      resistin, and visfatin, as well as cytokines and chemokines, such as TNF-alpha,
      IL-6, monocyte chemoattractant protein 1, and others. Proinflammatory molecules
      produced by adipose tissue have been implicated as active participants in the
      development of insulin resistance and the increased risk of cardiovascular
      disease associated with obesity. In contrast, reduced leptin levels might
      predispose to increased susceptibility to infection caused by reduced T-cell
      responses in malnourished individuals. Altered adipokine levels have been
      observed in a variety of inflammatory conditions, although their pathogenic role
      has not been completely clarified.

PMID- 15867845
TI  - Does obesity weigh heavily on the health of the human airway?

PMID- 15867846
TI  - Obesity, smooth muscle, and airway hyperresponsiveness.
AB  - Both asthma and obesity are large and growing public health issues. Mounting
      evidence now implicates obesity as a major risk factor for asthma, thus linking
      these 2 major epidemics. Moreover, both in human subjects and in mice, obesity
      appears to predispose toward airway hyperresponsiveness. This review describes
      potential mechanisms whereby obesity might modify airway smooth muscle function
      to explain these observations. These mechanisms include both static and dynamic
      mechanical factors attributable to decreases in functional residual capacity and
      decreases in tidal volume that are observed in the obese. They include also
      obesity-related changes in lung development, chronic systemic inflammation
      (including increased serum levels of inflammatory cytokines and chemokines), and
      adipocyte-derived factors, including leptin, adiponectin, and plasminogen
      activator inhibitor.

PMID- 15867847
TI  - Physical activity and exercise in asthma: relevance to etiology and treatment.
AB  - There is little doubt that the cause of the increased prevalence and severity of
      asthma is multifactorial. Although the factors of allergen exposure and hygiene
      are almost certainly necessary for its development, there is a growing body of
      literature that implicates lifestyle change, specifically decreased physical
      activity, as a contributor to the increase in asthma prevalence and severity.
      Several literature reviews of exercise conditioning in patients with asthma have
      been published. These reviews and recent controlled trials emphasize that
      although many of the studies of exercise conditioning in asthmatic patients
      involved different methods and outcome measures, the overwhelming majority of
      studies demonstrated the capacity for asthmatic subjects to exercise safely and
      significantly improve their cardiovascular fitness and quality of life. There are
      several proposed pathophysiologic mechanisms responsible for the effects of
      decreased activity on the lung function of patients with asthma. A prescription
      for exercise has been endorsed for all asthmatic subjects by the American College
      of Sports Medicine and the American Thoracic Society. The allergy community has
      placed emphasis on medical therapy and allergen avoidance; in addition, exercise
      [correction] has not been formally incorporated into the National Asthma
      Education and Prevention Program guidelines. It is our belief that an exercise
      prescription should be part of the treatment for all cases of asthma. The real
      question is whether prolonged physical activity and, in particular, outdoor play
      of children plays a role in prophylaxis against persistent wheezing. If so, the
      decrease in physical activity might have played a major role in recent increases
      in asthma prevalence and severity.

PMID- 15867848
TI  - Patterns of asthma control: a 3-year analysis of patient claims.
AB  - BACKGROUND: The goal of asthma therapy is to maintain consistent control.
      OBJECTIVE: We sought to examine the patterns of asthma control recorded over 3
      years using administrative claims and resource utilization definition. METHODS:
      We performed a retrospective observational study with a nationally representative
      patient-level database containing pharmacy and medical claims. Patients with
      asthma (International Classification of Diseases, Ninth Revision-Clinical
      Modification code 493.xx), patients undergoing treatment with at least 1 asthma
      medication, and patients with 36 months of continuous claims coverage during the
      calendar years 1996 through 2002 were identified. A total of 63,324 patients were
      included in the study. Patients were classified as having controlled asthma in
      year 1 if they had less than 4 claims for a short-acting beta 2 -agonist, no
      claims for an OCS, and no asthma-related emergency department visits or
      hospitalizations. Patients were then followed over the next 8 quarters (2 years)
      to observe whether control was maintained. Control during a quarter was defined
      with the same criteria, except the reliever threshold was adjusted to 2 or more
      claims per quarter. RESULTS: Thirty-nine thousand ninety-five (57%) patients were
      defined as having controlled asthma during year 1. During the 2-year follow-up
      period, a range of 10% to 14% of these patients with controlled asthma met the
      criteria of uncontrolled asthma during any given quarter. Overall, 46,227 (73%)
      patients identified met the criteria for uncontrolled asthma at least once during
      the 3-year period. CONCLUSIONS: This study demonstrates that almost 75% of
      asthmatic patients experience an uncontrolled asthma episode 1 or more times over
      a 3-year period. Furthermore, we found that significant fluctuations in asthma
      control exist, even in patients with prior controlled asthma.

PMID- 15867849
TI  - Short-term lower-leg growth rate and urine cortisol excretion in children treated
      with ciclesonide.
AB  - BACKGROUND: Measurement of short-term lower-leg growth rate in children by means
      of knemometry has become established as an integral part of the available
      measures of systemic activity of topical steroids in children. OBJECTIVE: We
      sought to determine the effects of clinically effective doses of the novel
      inhaled corticosteroid ciclesonide on lower-leg growth rate and hypothalamic
      pituitary-adrenal axis function in children with asthma. METHODS: In a double
      blind, placebo-controlled, 4-period crossover study, 24 children aged 6 to 12
      years sequentially received ciclesonide (40, 80, and 160 microg) in randomized
      order once daily in the evening. Each 2-week treatment period was followed by a 2
      week washout period. Knemometry was performed at the beginning and end of each
      treatment period. Cortisol levels in 12-hour overnight urine were measured at the
      end of each treatment period. RESULTS: No statistically significant differences
      were seen in lower-leg growth rates between any of the ciclesonide treatments and
      placebo. Lower-leg growth rates were 0.412 mm/wk for placebo, 0.425 mm/wk for 40
      microg of ciclesonide, 0.397 mm/wk for 80 microg of ciclesonide, and 0.370 mm/wk
      for 160 microg of ciclesonide. There was no statistically significant dose
      response effect. Likewise, no statistically significant differences or dose
      response effects were found for urinary cortisol adjusted for creatinine.
      CONCLUSION: Short-term lower-leg growth rate and hypothalamic-pituitary-adrenal
      axis function are not affected by treatment with ciclesonide in doses intended
      for clinical use in children.

PMID- 15867850
TI  - Allergen exposure in infancy and the development of sensitization, wheeze, and
      asthma at 4 years.
AB  - BACKGROUND: The relationship between mite and pet allergen exposure in infancy
      and the subsequent development of sensitization and asthma is complex. OBJECTIVE:
      We prospectively investigated the effect of allergen exposure at 3 months of age
      on the development of sensitization, wheeze, and physician-diagnosed asthma in
      the first 4 years of life in a birth cohort of children with and without an
      atopic mother. METHODS: Children participated in the Prevention and Incidence of
      Asthma and Mite Allergy study. Allergen exposure at 3 months of age was
      determined from mattress dust samples. Specific IgE to inhalant allergens was
      measured at 4 years of age, and information about wheeze and physician-diagnosed
      asthma was collected with yearly questionnaires. RESULTS: Mite and cat allergen
      exposure in infancy were associated with an increased risk of specific
      sensitization to house dust mite and cat, respectively, at 4 years of age. There
      were borderline significant associations between cat allergen exposure and
      persistent wheeze in the total study population and between dog allergen exposure
      and persistent wheeze in children with a nonatopic mother. In children with an
      atopic mother, there was some indication of a positive association between mite
      allergen exposure and physician-diagnosed asthma. CONCLUSION: Early house dust
      mite and cat allergen exposure might lead to sensitization and, in case of cat
      allergen exposure, to persistent wheeze. Early mite and dog allergen exposure
      might lead to asthma and persistent wheeze, respectively, but only in subgroups
      defined by maternal atopy.

PMID- 15867851
TI  - Allergy and asthma.
AB  - Initiation and regulation of allergic inflammation is influenced by many factors,
      including cell type, membrane receptors, and mediators generated. Furthermore,
      the altered response of targeted tissues (ie, airway smooth muscle) becomes
      important to the eventual expression of asthma. Finally, the genetic regulation
      and association of genetic polymorphisms has enhanced our understanding of host
      susceptibility. In this review key findings published in 2004 issues of the
      Journal of Allergy and Clinical Immunology are highlighted to demonstrate recent
      advances in these areas.

PMID- 15867852
TI  - Beta2-Adrenergic receptor polymorphism and asthma: true or false?

PMID- 15867853
TI  - Meta-analysis of the association of beta2-adrenergic receptor polymorphisms with
      asthma phenotypes.
AB  - BACKGROUND: Two common polymorphisms of the beta2-adrenergic receptor gene
      (Arg16Gly and Gln27Glu ) have been extensively studied for their possible
      association with asthma-related phenotypes, but the results of individual studies
      have been inconclusive. OBJECTIVE: We aimed to integrate quantitatively the
      available evidence on the association of the Arg16Gly and the Gln27Glu
      polymorphisms with asthma, nocturnal asthma, asthma severity, and bronchial
      hyperresponsiveness. METHODS: Meta-analysis of case-control and cohort studies
      using random effects models. RESULTS: A total of 28 studies were included in the
      meta-analysis. The summary estimates suggested that neither the Gly16 nor the
      Glu27 allele contributes to asthma susceptibility overall (odds ratio [OR], 1.01;
      95% CI, 0.90-1.13; and OR, 0.95; 95% CI, 0.83-1.09, respectively) or to bronchial
      hyperresponsiveness (OR, 0.90; 95% CI, 0.77-1.05; and OR, 1.07; 95% CI, 0.94
      1.22, respectively). There was a strong association of Gly16 with nocturnal
      asthma (OR, 2.20; 95% CI, 1.56-3.11) and a less strong association with severe or
      moderate rather than milder asthma (OR, 1.42; 95% CI, 1.04-1.94). No such effects
      were seen for the Glu27 allele (OR, 1.02; 95% CI, 0.74-1.40; and OR, 0.82; 95%
      CI, 0.59-1.14, respectively). Moreover, there was evidence that Gly16 homozygotes
      had a much higher risk for nocturnal asthma (OR, 5.15; 95% CI, 2.44-10.84) and
      asthma severity (OR, 2.84; 95% CI, 1.62-4.96) than the Arg16 homozygotes.
      CONCLUSION: The Gly16 allele of the beta2-adrenergic receptor gene predisposes to
      nocturnal asthma, and this may also explain the association with asthma severity.
      Neither polymorphism modulates the risk for bronchial hyperresponsiveness or mild
      asthma.

PMID- 15867854
TI  - IFN-gamma-enhanced allergen penetration across respiratory epithelium augments
      allergic inflammation.
AB  - BACKGROUND: Respiratory allergen contact is the critical event in the elicitation
      and boosting of allergen-specific immune responses, as well as in the induction
      of immediate and late inflammatory reactions. OBJECTIVE: We sought to investigate
      the influence of various factors of allergic inflammation on the integrity and
      barrier function of respiratory epithelium for allergens. METHODS: We cultured
      the human bronchial epithelial cell line 16HBE14o- in a transwell culture system
      as a surrogate of intact respiratory epithelium and used purified iodine 125
      labeled recombinant major birch pollen allergen (rBet v 1) to study the extent,
      kinetics, and factors influencing transepithelial allergen penetration. RESULTS:
      Culture supernatants from activated allergen-specific T H 1 clones decreased
      transepithelial resistance. A screening of various factors (histamine, IFN-gamma,
      IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-8, IL-12, and TNF-alpha) identified IFN
      gamma as a potent factor capable of reducing epithelial barrier properties and
      enhancing transepithelial allergen penetration. Increased submucosal allergen
      concentrations caused by IFN-gamma-mediated reduction of epithelial barrier
      function provoked a more than 7-fold augmentation of histamine release from
      sensitized basophils. CONCLUSION: These results demonstrate that the T H 1 cell
      derived cytokine IFN-gamma facilitates allergen penetration through the
      respiratory epithelium and thereby can aggravate allergic inflammation.

PMID- 15867855
TI  - Genetic variants of the T-cell immunoglobulin mucin 1 but not the T-cell
      immunoglobulin mucin 3 gene are associated with asthma in an African American
      population.
AB  - BACKGROUND: The T-cell immunoglobulin mucin ( TIM ) proteins and their genetic
      variants have been suggested to play a role in regulating allergic diseases.
      OBJECTIVE: Genetic association of the sequence variants for TIM-1 and TIM-3 genes
      with asthma in an African American population was investigated. METHODS: Both
      case-control and family-based association analyses were performed for a total of
      7 polymorphisms, including 3 single nucleotide polymorphism (SNPs) and 1
      insertion/deletion polymorphism in the TIM-1 and 3 SNPs in the TIM-3 genes. The
      exposure to hepatitis A virus as judged by seropositivity was also examined.
      RESULTS: In the case-control design, the frequencies of the TT genotype for SNP
      rs2277025 and the homozygous deletion variant (157delMTTTVP) in the fourth exon
      of the TIM-1 gene were higher among patients with patients with asthma compared
      with the controls (odds ratio [OR], 2.779, P = .016; and OR, 3.09, P = .022,
      respectively). This association was substantiated by haplotype analysis of these
      and 2 additional SNPs (OR, 2.48; P = .004), and also by family-based tests for
      the allele and haplotype carrying 157delMTTTVP (P = .009 and P = .048,
      respectively). Furthermore, this association seems to exist even in the hepatitis
      A virus-seronegative subjects in our data. None of the 3 variants in TIM-3 genes
      yielded significant association with either asthma or asthma-related phenotypes.
      CONCLUSION: Our findings suggest that the genetic variants of the TIM-1 but not
      the TIM-3 gene contribute to asthma susceptibility in this African-American
      population.

PMID- 15867856
TI  - Effects of ciclesonide and fluticasone propionate on allergen-induced airway
      inflammation and remodeling features.
AB  - BACKGROUND: Several topical corticosteroids are available as anti-inflammatory
      treatment for asthma. Their comparative effects on allergic inflammation and
      airway remodeling are unclear. OBJECTIVE: We compared the effects of ciclesonide
      with those of fluticasone propionate in a Brown Norway rat model of chronic
      allergic asthma. METHODS: Rats sensitized and exposed to ovalbumin (OVA) were
      treated with dry powder vehicle, ciclesonide, or fluticasone (0.01, 0.03, and 0.1
      mg/kg administered intratracheally) 24 hours and 1 hour before each of 6 OVA
      exposures. In a second protocol we administered 0.1 mg/kg ciclesonide or
      fluticasone only after the third OVA exposure. RESULTS: Ciclesonide at all doses
      inhibited the allergen-induced increase in airway eosinophils and T cells,
      reduced goblet cell hyperplasia, and decreased 5-bromo-2'-deoxyuridine
      immunoreactive airway smooth muscle (ASM) and epithelial cells. At 0.03 and 0.1
      mg/kg ciclesonide, bronchial hyperresponsiveness (BHR) was also inhibited.
      Fluticasone did not attenuate allergen-induced BHR, despite inhibiting airway
      eosinophils and T cells, goblet cell hyperplasia, and 5-bromo-2'-deoxyuridine
      immunoreactive ASM and epithelial cells. Fluticasone (0.1 mg/kg) caused a
      significant reduction in body weight (9%) compared with ciclesonide (0.1 mg/kg).
      Ciclesonide did not change plasma corticosterone levels, whereas fluticasone (0.1
      mg/kg) reduced them. In the second protocol both fluticasone and ciclesonide
      inhibited BHR, bronchial inflammation, goblet cell hyperplasia, and ASM
      proliferation. CONCLUSION: Ciclesonide potently inhibited chronic allergic
      inflammation, remodeling, and BHR without having an effect on body weight and the
      hypothalamic-pituitary-adrenal axis. Fluticasone prevented airway inflammation
      but not BHR, but both fluticasone and ciclesonide are effective at reversal of
      BHR, inflammation, and remodeling features.

PMID- 15867857
TI  - Gradual increase in priming of human eosinophils during extravasation from
      peripheral blood to the airways in response to allergen challenge.
AB  - BACKGROUND: Eosinophils isolated from the blood of patients with allergic asthma
      exhibit enhanced responsiveness to multiple stimuli compared with cells from
      normal controls, a phenomenon generally referred to as priming . This priming
      response is essential for optimal activation with augmented responses including
      chemotaxis, cytotoxicity, respiratory burst, and the release of proinflammatory
      lipid mediators. OBJECTIVE: To monitor the kinetics of priming of eosinophils in
      the peripheral blood and in the bronchoalveolar lavage fluid of patients with
      allergic asthma before and after allergen challenge. METHODS: Priming of blood
      eosinophils obtained from patients with allergy and donors without allergy was
      measured by labeling with monoclonal phage antibodies A17 and A27 recognizing
      priming-associated epitopes on phagocytes. In addition, blood and bronchoalveolar
      lavage fluid eosinophils from subjects with allergy after segmental and whole
      lung allergen challenge were similarly analyzed. RESULTS: A dose-dependent
      cytokine-induced upregulation of priming-associated epitopes on blood eosinophils
      was found. Patients with allergic asthma exhibited an in vivo partially primed
      eosinophil phenotype, which is further primed in vitro after cytokine or
      chemokine incubation. Priming was increased in peripheral blood 6 hours after
      whole lung challenge as well as after segmental allergen challenge.
      Interestingly, eosinophils obtained from the bronchoalveolar lavage fluid 48
      hours after segmental allergen challenge exhibited a higher primed phenotype.
      CONCLUSION: These data are consistent with a model in which local allergic
      inflammatory reactions induce partial systemic eosinophil priming in the
      peripheral blood. Eosinophils found in the airway are highly primed, consistent
      with the markedly upregulated inflammatory capacity observed in these cells.

PMID- 15867858
TI  - Different profiles of T-cell IFN-gamma and IL-12 in allergen-induced early and
      dual responders with asthma.
AB  - BACKGROUND: IFN-gamma and IL-12 are anti-inflammatory cytokines released from
      various cells, including T cells. Allergen inhalation by atopic subjects with
      asthma results in 2 bronchoconstrictor phenotypes, termed isolated early and dual
      responders . Persistence of allergen-induced airway response and inflammation is
      a distinctive feature of dual responders. OBJECTIVE: To evaluate the roles of IFN
      gamma and IL-12 in resolving allergen-induced airway inflammation by comparing T
      lymphocytes (CD4 + and CD8 + cells) producing these cytokines in isolated early
      and dual responders. METHODS: Twenty-four subjects with asthma (12 isolated early
      and 12 dual responders) were challenged with inhaled allergen. Peripheral blood
      and induced sputum were taken before and 1 day, 3 days, and 7 days after
      challenge. Frequency of IFN-gamma, IL-12, IL-4, and IL-13 producing CD4 + and CD8
      + cells was assessed by using flow cytometry. RESULTS: After allergen, both CD4 +
      and CD8 + IFN-gamma positive cells in peripheral blood significantly decreased in
      dual responders only, whereas CD4 + and CD8 + IFN-gamma positive cells in induced
      sputum significantly increased in isolated early responders only. By contrast, IL
      12 positive cells in peripheral blood significantly increased after allergen
      challenge only in isolated early responders. The ratio of CD4 + and CD8 + IL
      4/IFN-gamma positive cells in peripheral blood significantly decreased in
      isolated early responders by 3 days and had recovered by 7 days. CONCLUSION:
      These results suggest that contrasting profiles of IFN-gamma and IL-12 production
      may be responsible for different time courses of allergen-induced airway
      responses between isolated early and dual responders.

PMID- 15867859
TI  - A hybrid molecule resembling the epitope spectrum of grass pollen for allergy
      vaccination.
AB  - BACKGROUND: Allergy vaccines based on natural allergen extracts contain greatly
      varying amounts of individual allergens with different immunogenicity. OBJECTIVE:
      To develop a novel type of allergy vaccine for complex allergen sources that
      combines defined amounts of the major allergens in the form of single hybrid
      molecules. METHODS: A hybrid molecule was engineered by PCR-based mending and
      expression of the cDNAs coding for the 4 major grass pollen allergens and
      compared with its single components by circular dichroism analysis, T-cell
      proliferation, ELISA competition, and histamine release assays. Immune responses
      to the hybrid molecule were studied in BALB/c mice and rat basophil leukemia
      assays. RESULTS: The hybrid contained most of the B-cell epitopes of grass pollen
      and could be used to diagnose allergy in 98% (n = 652) of patients allergic to
      grass pollen. Immunization of mice and rabbits with the hybrid induced stronger
      and earlier IgG antibody responses than equimolar mixtures of the components,
      which can be explained by the induction of stronger T-cell responses by the
      hybrid versus the individual components. IgG antibodies induced by vaccination
      with the hybrid blocked immediate allergic reactions, as demonstrated by rat
      basophil degranulation assays in a murine model of grass pollen allergy.
      CONCLUSION: We demonstrate for grass pollen allergy that recombinant hybrid
      molecules covering the spectrum of the disease-eliciting epitopes of complex
      allergen sources can be engineered.

PMID- 15867860
TI  - Treatment of nasal polyposis and chronic rhinosinusitis with fluticasone
      propionate nasal drops reduces need for sinus surgery.
AB  - BACKGROUND: Steroid treatment is the mainstay of therapy for nasal polyps and
      rhinosinusitis. Oral steroids have considerable systemic side effects, and nasal
      sprays do not sufficiently reach the middle meatus, where polyps originate. Nasal
      drops might be a more useful formula to deliver steroids into the middle meatus.
      OBJECTIVE: We sought to investigate whether treatment with fluticasone propionate
      nasal drops (FPNDs) can reduce the need for surgery, as measured by signs and
      symptoms of nasal polyposis and chronic rhinosinusitis, in patients who are on
      the waiting list for functional endoscopic sinus surgery (FESS). METHODS: Fifty
      four patients (28 male) with severe nasal polyposis, chronic rhinosinusitis, or
      both indicated for FESS were included in a 12-week, double-blind, placebo
      controlled study. Use of intranasal steroid spray was stopped at least 4 weeks
      before randomization. Signs and symptoms were recorded before, during, and at the
      end of the study period. At the end of the study, a computed tomographic scan was
      performed, and the need for operation was reassessed by using a standardized
      scoring method. RESULTS: FESS was no longer required in 13 of 27 patients treated
      with FPNDs versus 6 of 27 in the placebo group (P < .05). Six patients from the
      placebo group dropped out versus 1 from the FPND group. Symptoms of nasal
      obstruction, rhinorrhea, postnasal drip, and loss of smell were reduced in the
      FPND group (P < .05). Peak nasal inspiratory flow scores increased significantly
      (P < .01). Polyp volume decreased in the FPND group (P < .05), and computed
      tomographic scores improved in both groups (P < .05). CONCLUSION: Treatment with
      FPNDs in patients indicated for FESS can reduce the need for surgery.

PMID- 15867861
TI  - The asthma and obesity epidemics: the role played by the built environment--a
      public health perspective.
AB  - Obesity and asthma have reached epidemic proportions in the United States. The
      reasons for these epidemics are complex, and the solutions to address them are
      many. This article explores the epidemics, their causes and consequences,
      associations and relationships, an expansion of the definition of the
      environment, and current national initiatives that address the components of the
      built and social environments that promote obesity and precipitate asthma.

PMID- 15867862
TI  - Quantitative measurement of IgE antibodies to purified allergens using
      streptavidin linked to a high-capacity solid phase.
AB  - BACKGROUND: Commercially available assays for IgE antibody provide results in
      international units per milliliter for many allergen extracts, but this is not
      easily achieved with purified or novel allergens. OBJECTIVE: To develop assays
      for IgE antibody suitable for purified or novel allergens by using a commercially
      available immunosorbent. METHODS: Streptavidin coupled to a high-capacity
      immunosorbent (CAP) was used to bind biotinylated purified allergens from mite
      (Der p 1 and Der p 2), cat (Fel d 1), and dog (Can f 1). Assays for IgE antibody
      to these allergens were performed on sera from children (asthma and control) as
      well as adults with atopic dermatitis. RESULTS: The results were validated by
      serial dilution of sera with high and low levels of IgE antibody and were
      quantitated in international units per milliliter by using a standard curve.
      Values for IgE antibody to Der p 1, Der p 2, and Fel d 1 correlated with values
      obtained with the allergen extracts (r2 = 0.80, 0.84, and 0.95, respectively; P <
      .001 in each case). Furthermore, the values for IgE antibody in sera from
      children with high exposure to mite and cat allergens demonstrated 10-fold higher
      levels of IgE antibody to Der p 1 and Der p 2 than to Fel d 1 (P < .001).
      CONCLUSION: The streptavidin immunosorbent technique provides a new method for
      quantifying IgE antibody to purified proteins. The results provide evidence about
      the high quantities of IgE antibody to purified inhalant allergens in patients
      with atopic dermatitis. In addition, the results demonstrate major differences in
      IgE antibodies specific for mite and cat allergens among children with high
      exposure to both allergens.

PMID- 15867863
TI  - Frequency of beryllium-specific, TH1-type cytokine-expressing CD4+ T cells in
      patients with beryllium-induced disease.
AB  - BACKGROUND: Beryllium sensitization is caused by exposure to beryllium in the
      workplace. A subset of beryllium-sensitized (BeS) subjects progress to chronic
      beryllium disease (CBD), a disorder characterized by a CD4+ T-cell alveolitis and
      granulomatous inflammation. Whether biomarkers are present in blood that would
      allow separation of CBD from beryllium sensitization without invasive pulmonary
      procedures is unknown. OBJECTIVE: The aim of this study was to determine whether
      the quantity of beryllium-specific T cells in blood of patients with CBD differs
      from that found in BeS subjects. METHODS: Beryllium-induced T-cell proliferation
      and T H 1-type cytokine secretion were determined in blood cells from 33 patients
      with CBD and 18 BeS subjects. RESULTS: We demonstrate here that patients with CBD
      have a significantly elevated number of IFN-gamma-producing and IL-2-producing
      beryllium-specific CD4+ T cells in blood compared with both BeS and normal
      control subjects. In contrast, no difference in beryllium-induced proliferation
      of blood T cells was seen between BeS patients and patients with CBD. Compared
      with the blood beryllium lymphocyte proliferation test, which detected beryllium
      induced proliferation in 65% of BeS patients and patients with CBD, ELISPOT
      analysis detected IFN-gamma secretion in 80% of these subjects. Higher numbers of
      beryllium-specific cells in blood were also associated with the extent of
      alveolar inflammation, as measured by both bronchoalveolar lavage white blood
      cell and lymphocyte counts. CONCLUSION: The frequency of beryllium-specific T
      cells in the blood of beryllium-exposed subjects may be a useful biomarker that
      helps discriminate between beryllium sensitization and progression to CBD.

PMID- 15867864
TI  - Fungal fragments and undocumented conidia function as new aeroallergen sources.
AB  - BACKGROUND: More than 100 genera of fungal conidia are currently recognized as
      sources of allergens. The contribution of other fungal genera plus airborne
      fungal hyphae and fragmented conidia to allergic diseases is poorly understood.
      OBJECTIVE: We sought to investigate the expression of allergens from airborne
      wild-type fungi using the Halogen immunoassay, which uses allergic serum IgE to
      immunostain immobilized allergens extracted from individual fungal particles.
      METHODS: Airborne fungi were collected onto mixed cellulose ester protein-binding
      membranes for 2.5 hours with volumetric air pumps. Collected fungi were incubated
      overnight in a humid chamber to promote the germination of conidia. The membranes
      were laminated with an adhesive cover slip and immunostained with an Alternaria
      species-sensitive serum IgE pool. The samples were examined by means of light
      microscopy, and positively immunostained fungal particles were classified and
      counted. RESULTS: All air samples contained fungal hyphae that expressed soluble
      allergens and were significantly higher in concentration than counts of conidia
      of individual well-characterized allergenic genera (P < .05). Resultant
      immunostaining of fungal hyphae was heterogeneous, and approximately 25% of all
      hyphae expressed detectable allergen compared with nonstained hyphae (P < .05).
      Fungal conidia of 10 genera that were previously uncharacterized as allergen
      sources were shown to demonstrate IgE binding to expressed antigens and accounted
      for 8% of the total airborne conidia count. CONCLUSIONS: Our analysis of wild
      type fungi collected indoors presents a new paradigm of natural fungal exposure,
      which, in addition to commonly recognized species, implicates airborne hyphae,
      fragmented conidia, and the conidia of a much more diverse range of genera as
      airborne allergens.

PMID- 15867865
TI  - Relationships among quality of life, severity, and control measures in asthma: an
      evaluation using factor analysis.
AB  - BACKGROUND: Validated psychometric tools measuring quality of life, asthma
      control, and asthma severity have been developed, but their relationships with
      each other and with other important patient-centered outcomes have not been
      rigorously assessed. OBJECTIVE: To use factor analysis to evaluate the
      relationships of these validated tools with each other and with other patient
      centered outcomes. METHODS: Surveys were completed by a random sample of 2854
      Health Maintenance Organization members age 18 to 56 years with persistent
      asthma. Surveys included demographic information; validated tools measuring
      generic (Short Form-12; SF-12) and asthma-specific (Juniper Mini Asthma Quality
      of Life Questionnaire; AQLQ) quality of life, asthma control (Asthma Therapy
      Assessment Questionnaire), and asthma symptom severity (Asthma Outcomes
      Monitoring System); self-described severity, control, and course over time; and
      history of acute exacerbations. RESULTS: Principal component analysis suggested a
      5-factor model that accounted for approximately 59% of the variability. The most
      prominent rotated factor reflected asthma symptom frequency (19.4% of
      variability), was measured by the symptom subscale of the AQLQ, and was the only
      factor significantly related to the Asthma Therapy Assessment Questionnaire,
      Asthma Outcomes Monitoring System, or the self-reported assessments of severity,
      control, or course. Other factors included symptom bother (12.1% of variability),
      reflected by the environment and emotion AQLQ subscales; activity limitation
      (13.9% of variability), reflected by the activity AQLQ subscale and the SF-12
      physical component scale; mental health (8.3% of variability), reflected by the
      SF-12 mental component scale; and acute exacerbations (5.0% of variability), not
      measured by any of the validated scales. CONCLUSION: Distinct components of
      patient-reported asthma health status can be identified by factor analysis.
      Distinct constructs of severity versus control cannot be identified by the use of
      these tools alone.

PMID- 15867866
TI  - Polymorphisms in the 5' region of the CD14 gene are associated with eczema in
      young children.
AB  - BACKGROUND: Variants in the CD14 gene (CD14) are hypothesized to be associated
      with atopic disorders. However, most studies have only investigated one
      polymorphism in this gene. OBJECTIVE: We sought to study the association of 5
      single nucleotide polymorphisms (SNPs) in the 5' flanking region of CD14 with
      eczema and serum IgE levels in young children. METHODS: We genotyped 5 SNPs in an
      approximately 6.5-kb region in the 5' region of CD14 in 344 2-year-old white
      children from 2 birth cohorts in the northeastern United States. We examined the
      relation of both single SNPs and haplotypes in CD14 with the atopic outcomes.
      RESULTS: Two SNPs were significantly associated with eczema. In dominant models
      adjusted for potential confounders, SNP rs2569193 was associated with
      significantly decreased risk for eczema (odds ratio [OR] for CT/TT vs CC, 0.5;
      95% CI, 0.3-0.8), whereas SNP rs2569190 (also reported as the C-159T) was
      associated with significantly increased risk for eczema (OR for CT/TT vs CC, 2.3;
      95% CI, 1.4-3.8). The CT/TT genotypes of SNP rs2569190 also had higher geometric
      means of serum IgE than the CC genotype (24.6 vs 15 IU/mL, P = .025). Haplotype
      analyses provided results similar to those of the single SNP analyses.
      CONCLUSIONS: Our results contradict previous reports that have found a protective
      effect of the T allele of SNP rs2569190 (C-159T) against atopic disorders.
      Nevertheless, these results confirm the importance of polymorphisms in CD14 in
      the development of atopy, and future studies of this gene region will need to
      account for linkage disequilibrium and environmental exposures unique to the
      study population.

PMID- 15867867
TI  - Increased expression of osteopontin is associated with long-term bee venom
      immunotherapy.
AB  - BACKGROUND: Venom allergen immunotherapy (VIT) is proven to be highly effective
      for insect allergy, but the mechanisms and the biomarkers associated with
      clinical efficacy remain elusive. OBJECTIVE: The aim of this study was to
      identify candidate biomarkers associated with successful VIT. METHODS: Gene chip
      array and clustering analyses of PBMCs from subjects with or without VIT were
      performed. RESULTS: From gene chip array and clustering analyses, an increased
      expression of osteopontin was found in patients who completed 5 to 6 years of VIT
      and discontinued therapy for 3 to 6 years (completed treatment group) compared
      with the untreated group. A significantly higher level of serum osteopontin was
      found in the completed treatment group compared with the untreated group (n = 16
      in each group; P < .001). CONCLUSION: The upregulation of osteopontin after VIT
      suggests a role of osteopontin as a candidate biomarker for VIT.

PMID- 15867868
TI  - IgE-mediated and T cell-mediated autoimmunity against manganese superoxide
      dismutase in atopic dermatitis.
AB  - BACKGROUND: Autoreactivity of patients with atopic dermatitis (AD) to human
      proteins has been postulated as a decisive pathogenetic factor for AD. OBJECTIVE:
      In this study, it was investigated whether the stress-inducible enzyme manganese
      superoxide dismutase (MnSOD) of human and fungal origin might act as an
      autoallergen in atopic dermatitis. METHODS: Patients with AD (n = 69; mean SCORAD
      [SCORing Atopic Dermatitis], 27) and other inflammatory skin diseases as well as
      with inhalant allergies were investigated. The presence of specific IgE against
      recombinant MnSOD of fungal and human origin and the fungal extracts of
      Aspergillus fumigatus and Malassezia sympodialis was measured by CAP, ELISA, skin
      prick test, and in subset of patients also by atopy patch tests (APTs) and PBMC
      proliferation assays. Cross-reactivity between allergens was determined by CAP
      inhibition. The presence of MnSOD in human skin in various inflammatory skin
      conditions was investigated by immunohistochemistry. RESULTS: Specific IgE
      antibodies against human MnSOD correlating with the disease activity were found
      in 29 out of 67 patients with AD. The human protein was able to induce in vitro T
      cell reactivity and eczematous reactions in APT in MnSOD-sensitized patients with
      AD. MnSOD was upregulated in various inflammatory skin reactions and APT skin
      specimens. Cosensitization to structurally related and cross-reacting fungal
      MnSOD and the skin-colonizing yeast M sympodialis was observed in all patients
      sensitized against human MnSOD. CONCLUSION: Human MnSOD may play a role as an
      autoallergen in a subset of patients with AD, including nonatopic eczema. By
      molecular mimicry leading to cross-reactivity such sensitization might be induced
      primarily by exposure to environmental fungal MnSOD of M sympodialis .

PMID- 15867869
TI  - Food allergen sensitization in inner-city children with asthma.
AB  - BACKGROUND: Asthma continues to be an increasing cause of morbidity in the
      pediatric population, and studies have shown an association between food
      sensitivity and asthma. OBJECTIVE: We investigated the degree of food allergen
      sensitization in inner-city patients with asthma. METHODS: Five hundred four
      random serum samples from the National Cooperative Inner City Asthma Study were
      evaluated for specific IgE (UniCap) to 6 common food allergens (egg, milk, soy,
      peanut, wheat, and fish). Statistical analyses were performed to determine food
      sensitization prevalence and its association with asthma morbidity. RESULTS:
      Forty-five percent of patients had evidence of sensitization (food-specific IgE >
      or = 0.35 kU/L) to at least 1 food. Nineteen percent had IgE levels at > or = 50%
      positive predictive value for clinical reactivity to at least 1 food, with 4% of
      patients having levels > 95% positive predictive value for food allergy. Children
      sensitized to foods had higher rates of asthma hospitalization (P < .01) and
      required more steroid medications (P = .025). Sensitization to foods also
      correlated with sensitization to more indoor and outdoor aeroallergens (P <
      .001). CONCLUSION: Food allergen sensitization is highly prevalent in the inner
      city population with asthma, and it is associated with increased asthma
      healthcare and medication use. Therefore, food allergen sensitivity may be a
      marker for increased asthma severity.

PMID- 15867870
TI  - Intracellular cytokines may model immunoregulation of abacavir hypersensitivity
      in HIV-infected subjects.
AB  - BACKGROUND: The clinical treatment of patients with HIV and adverse drug events
      may be enhanced by an understanding of the underlying mechanisms. About 4% of
      patients with HIV receiving the potent antiretroviral drug abacavir develop a
      hypersensitivity reaction. This idiosyncratic reaction appears to have an
      immunologic component that has yet to be defined. Given that the T-cell type 2
      cytokine IL-4 may be overproduced by patients with allergy or other immunologic
      dysregulation, an index cytokine profile could help elucidate the character of a
      drug-specific hypersensitivity reaction. OBJECTIVE: Quantitation of the
      production of the type 2 IL-4 and the counterregulatory type 1 cytokine IFN-gamma
      in patients with abacavir-related hypersensitivity. METHODS: Intracellular
      cytokines were enumerated in blood T cells by flow cytometry. Subjects were
      grouped for evaluation as patients with a hypersensitive response after abacavir
      treatment, patients initiating abacavir who also were evaluated again after 1
      month on abacavir, patients on abacavir for 6 months without hypersensitivity,
      and HIV-naive control individuals. RESULTS: There was a significant association
      between increased IL-4 production by CD4 and CD8 T lymphocytes and
      hypersensitivity reactions to abacavir. Lymphocytes from hypersensitive subjects
      expressed CD28 and the anti-HIV chemokine macrophage inflammatory protein 1beta
      with a frequency comparable with HIV-naive control cells, suggesting the
      possibility that the activated T cells from patients with hypersensitivity are
      functional. CONCLUSION: The expansion of type 0 and type 2 T cells phenotyped by
      IL-4 production may correlate with abacavir-associated hypersensitivity. The data
      suggest a cytokine bias that may facilitate B-cell differentiation and
      downregulate T-cell cytotoxic responses.

PMID- 15867871
TI  - Autoimmune chronic urticaria associated with type 1 diabetes and Graves' disease.

PMID- 15867872
TI  - COX-2-selective inhibitor valdecoxib induces severe allergic skin reactions.

PMID- 15867873
TI  - Eosinophilic esophagitis is frequently associated with IgE-mediated allergic
      airway diseases.

PMID- 15867874
TI  - Use of GM-CSF in the treatment of colitis associated with chronic granulomatous
      disease.

PMID- 15867875
TI  - Has the cost-effectiveness of Xolair (omalizumab) been underestimated?

PMID- 15867876
TI  - Cold temperature challenges for acquired cold urticaria.

PMID- 15867877
TI  - Mast cell degranulation after endobronchial adenosine challenge.

PMID- 15867878
TI  - Obesity and pulmonary function testing.

PMID- 15867879
TI  - Obesity, allergy and immunology.

PMID- 15867890
TI  - Improving health outcomes: future directions in the field.

PMID- 15867891
TI  - Beyond energy balance: there is more to obesity than kilocalories.
AB  - Using an epidemiologic model of the interactions between environmental agents and
      human hosts to explain obesity, we explored food, medications, physical
      inactivity, toxins, and viruses as environmental agents that interact with a
      genetically programmed host to disturb energy balance and cause obesity. Large
      portion sizes, high fat intakes, easy access to calorically sweetened beverages,
      and lack of any need to be physically active all play a role in the toxic
      environment that leads to obesity. The genetic and physiologic responses of a
      host determine whether or not this toxic environment will produce obesity.
      Reversing the current trends of obesity requires a new look at the limits of the
      energy balance concept, and a better understanding of how environmental factors
      acutely and chronically change the responses of susceptible hosts.

PMID- 15867892
TI  - Energetics of obesity and weight control: does diet composition matter?
AB  - Greater average weight losses (2.5 kg over 12 weeks) have been reported for low
      carbohydrate diets (<90 g/day) compared with traditional low-fat (<25% of
      energy), hypocaloric diets, implying a 233 kcal/day greater energy deficit. It
      has therefore been suggested that a low-carbohydrate diet may provide a metabolic
      advantage (an increase in energy expenditure), resulting in a positive effect on
      weight loss and maintenance. However, a review of studies in which 24-hour energy
      expenditure was measured did not provide evidence to support a metabolic
      advantage of low-carbohydrate diets and showed little evidence of a metabolic
      advantage of high-protein (>25% of energy) diets. Nonetheless, diets high in
      protein, but either low or modest in carbohydrate, have resulted in greater
      weight losses than traditional low-fat diets. We speculate that it is the
      protein, and not carbohydrate, content that is important in promoting short-term
      weight loss and that this effect is likely due to increased satiety caused by
      increased dietary protein. It has been suggested that the increased satiety might
      help persons to be more compliant with a hypocaloric diet and achieve greater
      weight loss. The current evidence, combined with the need to meet all nutrient
      requirements, suggests that hypocaloric weight-loss diets should be moderate in
      carbohydrate (35% to 50% of energy), moderate in fat (25% to 35% of energy), and
      protein should contribute 25% to 30% of energy intake. More studies of the
      efficacy of weight-loss and weight-maintenance diets that address protein content
      are needed. In addition, controlled studies of total energy expenditure or
      physical activity measured under free-living conditions that directly compare
      high-protein diets with those containing low and moderate carbohydrate content
      should also be performed.

PMID- 15867893
TI  - Gene-diet interactions on body weight changes.
AB  - Obesity is one of the most pressing problems in the industrialized world. The
      susceptibility to obesity is partly determined by genetic factors, but an
      "obesity-promoting environment" is typically necessary for its phenotypic
      expression. Such a genetically mediated susceptibility to environmental exposure
      is referred to as gene-environment interaction. This article reviews the effect
      of genotype-diet interactions on body weight and body composition changes. A few
      well-controlled studies with monozygotic twins have specifically addressed the
      genetic background of interindividual variation in response to overfeeding or
      energy restriction. Some individuals will gain or lose weight more easily than
      others, but subjects sharing the same genotype (monozygotic twins) will respond
      in a similar way, suggesting that the responsiveness to diet is mediated by their
      genotype. Further evidence for gene-environment interactions comes from candidate
      gene studies. Genes involved in pathways regulating energy expenditure and food
      intake may play a role in the predisposition to obesity. For example, DNA
      sequence variation in genes encoding the adrenergic receptors and uncoupling
      proteins are of particular relevance. This growing body of research may help in
      the development of antiobesity treatments and perhaps genetic tests to predict
      the risk for obesity.

PMID- 15867894
TI  - Behavioral interventions for obesity.
AB  - Because of the increased risk of comorbid conditions such as type 2 diabetes,
      hypertension, and osteoarthritis, and the high health care costs associated with
      obesity, researchers and clinicians continually search for low-cost and effective
      treatments for weight loss and weight maintenance. In this article we provide an
      overview of the principles of behavior modification as applied to the treatment
      of obesity, examine the benefits of augmenting behavioral interventions with
      pharmacotherapy, and review the use of less-traditional applications of behavior
      modification in the treatment of obesity, specifically Internet interventions,
      meal replacements, and telephone interventions. Based on our review, we conclude
      that these less-traditional approaches can be used effectively to apply the
      principles of behavior modification, specifically stimulus control and self
      monitoring, to obese patients. Future directions for research are outlined, which
      include examining the use of nontraditional behavioral interventions with
      children and the development of culturally sensitive interventions for racial and
      ethnic minority populations.

PMID- 15867895
TI  - Pediatric obesity epidemic: treatment options.
AB  - The increasing prevalence of overweight youth in the United States and the
      associated increase in medical comorbidities has created a growing need for
      effective weight-management interventions. The recommended treatment for an
      overweight child to achieve a more healthful weight uses four primary behavioral
      strategies: (a) reduce energy intake while maintaining optimal nutrient intake to
      protect growth and development, (b) increase energy expenditure by promoting more
      physical movement and less sedentary activity, (c) actively engage parents and
      primary caretakers as agents of change, and (d) facilitate a supportive family
      environment. Although this approach has the most empirical support, the impact on
      the pediatric obesity epidemic has been limited, particularly for adolescents
      with more severe obesity and for African-American, Native-American, and Hispanic
      children. This has prompted efforts to adapt strategies that have been effective
      in adult weight management for use in pediatric behavioral intervention programs.
      These include using motivational interviewing to increase readiness for health
      behavior changes, modifying the carbohydrate content of children's diets, using
      culturally appropriate messages and materials, improving cultural competency of
      health care providers, and using computer-based strategies. Randomized,
      controlled clinical trials are needed to test the safety and efficacy of these
      approaches before they can be recommended for clinical practice. Pharmacotherapy
      and bariatric surgery are more aggressive and historically adult interventions
      with greater risk that are being considered for severely obese adolescents who
      have serious obesity-related medical complications and who have failed other more
      conventional methods.

PMID- 15867897
TI  - Risk assessment of the overweight and obese patient.
AB  - Risk assessment of the overweight and obese patient is an important and necessary
      first step in the treatment process. Risk classification begins with
      determination of body mass index (BMI), waist circumference for those with a BMI
      of 35 or less, and presence of comorbid conditions. With the exception of
      measuring a fasting blood glucose and lipid panel on all patients, other
      diagnostic laboratory tests are selected based on the patient's risk factor
      status. Understanding the reasons leading to and sustaining the patient's
      overweight and obesity is the next major step and is paramount to designing
      individualized and targeted treatment. This information is ascertained by having
      the patient graph his or her weight pattern with associated life events and by
      assessing detailed dietary and physical activity histories. Calculating estimated
      energy balance has both benefits and limitations in clinical practice. Pediatric
      and geriatric patients represent special populations that require additional
      focus. Improvement in the assessment process will likely be achieved by using a
      team approach along with future developments in practical measurement of body
      composition and energy expenditure.

PMID- 15867898
TI  - Weight maintenance: what's missing?
AB  - Obesity has reached epidemic proportions in the United States, but there are few
      proven strategies for either preventing further weight gain or producing
      permanent weight loss. Our first priority should be to prevent the gradual weight
      gain experienced by much of the population. Although this will require less
      behavior change than producing and maintaining weight loss, helping Americans
      make and sustain the behavior changes needed to prevent gradual weight increases
      will be challenging. Because approximately 65% of Americans are already
      overweight or obese, we must also develop effective strategies to help achieve
      and maintain an amount of weight loss that improves their health and quality of
      life. Our real challenge is not in helping people lose weight but in helping them
      keep it off. Many programs have been shown to produce weight loss but few, if
      any, have been successful in maintenance of weight loss. Our challenge is in
      understanding how to help people keep off the weight they can lose in several
      ways.

PMID- 15867900
TI  - Family environment and pediatric overweight: what is a parent to do?
AB  - Although the causes of pediatric overweight are many and the levels of
      intervention required to prevent overweight in children extend from the child's
      immediate environment to the larger societal level, one critical intervention
      target is the parent. Scientific evidence points to specific dietary and physical
      activity/inactivity behaviors that families can adopt to encourage healthful
      weight status. Dietary recommendations include providing children with ample
      access to nutrient-dense foods and beverages and high-fiber foods, both at meals
      and snack times, reducing children's access to high-calorie, nutrient-poor
      beverages and foods both when eating at home and at restaurants, avoiding
      excessive food restriction or use of food as a reward, and encouraging children
      to eat breakfast on a daily basis. Physical activity recommendations include
      providing opportunities and encouragement for children to be physically active
      while reducing children's television and video game time. Parental modeling of
      healthful eating and physical activity practices is recommended to reinforce
      these patterns in youth. Dietetics professionals, physicians, and other health
      care professionals can assist parents in their efforts to prevent pediatric
      overweight by providing information and supporting these key behaviors, while
      working to create environments that support healthful lifestyle changes.

PMID- 15867901
TI  - ADA Evidence Analysis Library.

PMID- 15867902
TI  - Dietary supplements in weight reduction.
AB  - We summarize evidence on the role of dietary supplements in weight reduction,
      with particular attention to their safety and benefits. Dietary supplements are
      used for two purposes in weight reduction: (a) providing nutrients that may be
      inadequate in calorie-restricted diets and (b) for their potential benefits in
      stimulating weight loss. The goal in planning weight-reduction diets is that
      total intake from food and supplements should meet recommended dietary
      allowance/adequate intake levels without greatly exceeding them for all
      nutrients, except energy. If nutrient amounts from food sources in the reducing
      diet fall short, dietary supplements containing a single nutrient/element or a
      multivitamin-mineral combination may be helpful. On hypocaloric diets, the
      addition of dietary supplements providing nutrients at a level equal to or below
      recommended dietary allowance/adequate intake levels or 100% daily value, as
      stated in a supplement's facts box on the label, may help dieters to achieve
      nutrient adequacy and maintain electrolyte balance while avoiding the risk of
      excessive nutrient intakes. Many botanical and other types of dietary supplements
      are purported to be useful for stimulating or enhancing weight loss. Evidence of
      their efficacy in stimulating weight loss is inconclusive at present. Although
      there are few examples of safety concerns related to products that are legal and
      on the market for this purpose, there is also a paucity of evidence on safety for
      this intended use. Ephedra and ephedrine-containing supplements, with or without
      caffeine, have been singled out in recent alerts from the Food and Drug
      Administration because of safety concerns, and use of products containing these
      substances cannot be recommended. Dietitians should periodically check the Food
      and Drug Administration Web site ( www.cfsan.fda.gov ) for updates and warnings
      and alert patients/clients to safety concerns. Dietetics professionals should
      also consult authoritative sources for new data on efficacy as it becomes
      available ( ods.od.nih.gov ).

PMID- 15867903
TI  - Appetite: measurement and manipulation misgivings.
AB  - Humans appear to have a genotype that permits, or even encourages, an energy
      intake that is greater than energy expenditure when food is available. This was
      functional throughout most of human evolution but is less so in the current
      environment of inexpensive, palatable, and readily available foods. To achieve
      dietary goals of weight loss or maintenance, attempts have been made to influence
      appetitive sensations through the manipulation of the physical properties of
      foods, their composition, or their pattern of consumption. This has led to
      limited success, in part, because measurement of appetitive sensations is
      difficult but, more fundamentally, because the association between appetite and
      food choice or intake is not robust. This article critically reviews the most
      common methods for assessment of appetite and the effects of selected food
      constituents on appetitive sensations. Translation of current knowledge to
      dietetic practice must be made cautiously.

PMID- 15867904
TI  - Changing the energy density of the diet as a strategy for weight management.
AB  - A growing body of laboratory-based, clinical, and epidemiological data suggests
      that low-energy-dense diets are associated with better diet quality, lower energy
      intakes, and body weight. Dietary energy density can be lowered by adding water
      rich fruits, vegetables, cooked grains, and soups to the diet, and by reducing
      the diet's fat content. Low-energy-dense diets can be successfully incorporated
      into clinical dietetics since they help lower energy intake without reducing food
      volume and thus help individuals avoid feeling hungry and deprived. There are
      multiple steps that could be taken by nutrition professionals and food
      manufacturers to encourage the consumption of low-energy-dense diets. The goal is
      to develop reduced-calorie eating plans that meet personal food preferences and
      also provide satisfying food portions. Since using energy density to guide food
      choices leads to food patterns consistent with dietary guidelines, policy level
      initiatives should be devised to help ensure that low-energy-dense diets are
      affordable and accessible to all.

PMID- 15867905
TI  - Future and implications of reimbursement for obesity treatment.
AB  - Obesity has been defined as a distinct disease by the World Health Organization,
      National Institutes of Health, Centers for Disease Control and Prevention, and
      the American Dietetic Association. In the United States, a major reimbursement
      challenge is to promote acceptance of obesity as a chronic disease and acceptance
      of its treatment by health management organizations, private insurers, and the
      government. The United States health care system is focused on treating
      individual obesity-related diseases, but does not treat obesity as the underlying
      cause. Reimbursement of obesity treatments using "condition coverage" based on
      the presence of other diseases does not allow obesity to be treated independently
      as a disease in itself. It is necessary to make major investments in research to
      determine the best methods and to match the treatment with the individual, to
      prevent obesity in vulnerable populations, and to develop more effective drugs
      and treatments for those already overweight or obese. There should be a more
      detailed analysis of the cost of obesity, costs associated with obesity and
      obesity-related disease treatment, and costs of inaction. The obesity epidemic is
      too large to be ignored. Health care professionals have a duty to be informed
      about the disease and to advocate for patients who need help. Registered
      dietitians can be key players in delivering obesity treatment.

PMID- 15867906
TI  - Obesity and the built environment.
AB  - Biological, psychological, behavioral, and social factors are unable to fully
      explain or curtail the obesity epidemic. In this article we review research on
      the influence of the built environment on obesity. Studies were evaluated with
      regard to their methods of assessing the environment and obesity, as well as to
      their effects. Methods used to investigate the relationships between the built
      environment and obesity were found to be dissimilar across studies and varied
      from indirect to direct. Levels of assessment between and within studies varied
      from entire counties down to the individual level. Despite this, obesity was
      linked with area of residence, resources, television, walkability, land use,
      sprawl, and level of deprivation, showing promise for research utilizing more
      consistent assessment methods. Recommendations were made to use more direct
      methods of assessing the environment, which would include specific targeting of
      institutions thought to vary widely in relation to area characteristics and have
      a more influential effect on obesity-related behaviors. Interventions should be
      developed from the individual to the neighborhood level, specifically focusing on
      the effects of eliminating barriers and making neighborhood level improvements
      that would facilitate the elimination of obesogenic environments.

PMID- 15867907
TI  - Setting achievable goals for weight loss.

PMID- 15867908
TI  - Combined treatment for obesity and the metabolic syndrome.

PMID- 15867909
TI  - Expanding the limits of treatment--new strategic initiatives.
AB  - The perception that weight reduction is rarely successful is, in fact, a
      misperception. Between 1999-2000 and 2001-2002, there were no significant changes
      among adults in the prevalence of overweight, obesity, or extreme obesity, or
      among children aged 6 through 19 years in the prevalence of at risk for
      overweight. The National Heart, Lung, and Blood Institute defines successful long
      term weight loss as an intentional reduction of 10% from baseline maintained for
      1 year. Modest weight loss is not only beneficial but also achievable for persons
      with overweight and obesity. Of the Americans who have tried to lose weight,
      almost 50% have maintained their weight loss successfully for at least 1 year.
      The remaining half, those who seem unable to prevent or reverse their obesity,
      challenge dietetics professionals to mobilize resources, confront issues at the
      heart of the obesity epidemic, and develop new solutions. Work to date has paid
      off for millions of persons. We have stopped the epidemic of obesity. Now it is
      time to do more by joining health care practitioners with all other stakeholders
      in the effort to prevent and reverse it.

PMID- 15867910
TI  - Transient inhibition of BMP signaling by Noggin induces cardiomyocyte
      differentiation of mouse embryonic stem cells.
AB  - Embryonic stem (ES) cells are a promising source of cardiomyocytes, but clinical
      application of ES cells has been hindered by the lack of reliable selective
      differentiation methods. Differentiation into any lineage is partly dependent on
      the regulatory mechanisms of normal early development. Although several signals,
      including bone morphogenetic protein (BMP), Wnt and FGF, are involved in heart
      development, scarce evidence is available about the exact signals that mediate
      cardiomyocyte differentiation. While investigating the involvement of BMP
      signaling in early heart formation in the mouse, we found that the BMP antagonist
      Noggin is transiently but strongly expressed in the heart-forming region during
      gastrulation and acts at the level of induction of mesendoderm to establish
      conditions conducive to cardiogenesis. We applied this finding to develop an
      effective protocol for obtaining cardiomyocytes from mouse ES cells by inhibition
      of BMP signaling.

PMID- 15867911
TI  - Gene knockdown by large circular antisense for high-throughput functional
      genomics.
AB  - Single-stranded genomic DNA of recombinant M13 phages was tested as an antisense
      molecule and examined for its usefulness in high-throughput functional genomics.
      cDNA fragments of various genes (TNF-alpha, c-myc, c-myb, cdk2 and cdk4) were
      independently cloned into phagemid vectors. Using the life cycle of M13
      bacteriophages, large circular (LC)-molecules, antisense to their respective
      genes, were prepared from the culture supernatant of bacterial transformants. LC
      antisense molecules exhibited enhanced stability, target specificity and no need
      for target-site searches. High-throughput functional genomics was then attempted
      with an LC-antisense library, which was generated by using a phagemid vector that
      incorporated a unidirectional subtracted cDNA library derived from liver cancer
      tissue. We identified 56 genes involved in the growth of these cells. These
      results indicate that an antisense sequence as a part of single-stranded LC
      genomic DNA of recombinant M13 phages exhibits effective antisense activity, and
      may have potential for high-throughput functional genomics.

PMID- 15867912
TI  - A Chinese nano-society?

PMID- 15867914
TI  - Materials science in secondary education: clarification of funding sources for
      MRSEC initiatives.

PMID- 15867913
TI  - Materials science in secondary education: non-MRSEC initiatives.

PMID- 15867916
TI  - Dislocation dynamics: scars on a colloidal crystal ball.

PMID- 15867917
TI  - Ab initio modelling: genesis of crystal structures.

PMID- 15867919
TI  - Material witness: Fab DIY.

PMID- 15867918
TI  - Nanoparticle ensembles: nanocrystals come to order.

PMID- 15867921
TI  - EU basic research spending plans take shape.

PMID- 15867920
TI  - Nanostructured materials for advanced energy conversion and storage devices.
AB  - New materials hold the key to fundamental advances in energy conversion and
      storage, both of which are vital in order to meet the challenge of global warming
      and the finite nature of fossil fuels. Nanomaterials in particular offer unique
      properties or combinations of properties as electrodes and electrolytes in a
      range of energy devices. This review describes some recent developments in the
      discovery of nanoelectrolytes and nanoelectrodes for lithium batteries, fuel
      cells and supercapacitors. The advantages and disadvantages of the nanoscale in
      materials design for such devices are highlighted.

PMID- 15867922
TI  - Editor seeks strong-minded researchers for lively debate ...

PMID- 15867923
TI  - Phosphorylation-specific prolyl isomerization: is there an underlying theme?
AB  - The prolyl isomerase Pin1 is a conserved enzyme that is intimately involved in
      diverse biological processes and pathological conditions such as cancer and
      Alzheimer's disease. By catalysing cis-trans interconversion of certain motifs
      containing phosphorylated serine or threonine residues followed by a proline
      residue (pSer/Thr-Pro), Pin1 can have profound effects on phosphorylation
      signalling. The structural and functional differences that result from cis-trans
      isomerization of specific pSer/Thr-Pro motifs probably underlie most, if not all,
      Pin1-dependent actions. Phosphorylation-dependent prolyl isomerization by Pin1
      remains a unique mode for the modulation of signal transduction. Here, we provide
      an overview of the plethora of regulatory events that involve this unique enzyme,
      with a particular focus on oncogenic signalling and neurodegeneration.

PMID- 15867924
TI  - Talin's second persona.

PMID- 15867925
TI  - When domestiques rebel: kinesins, cadherins and neuronal proliferation.

PMID- 15867926
TI  - Extending the court for cortactin: from the cortex to the Golgi.

PMID- 15867927
TI  - Tea for three: control of fission yeast polarity.

PMID- 15867928
TI  - ATM: HIV-1's Achilles heel?

PMID- 15867929
TI  - Ephrin tempers two-faced synaptojanin 1.

PMID- 15867930
TI  - Dpp gets in shape.

PMID- 15867931
TI  - Ghost sparks.

PMID- 15867932
TI  - IRF-7 triggers the interferon alarm.

PMID- 15867937
TI  - Quantifying the passive extensibility of the flexor pollicis longus muscle in
      people with tetraplegia.
AB  - STUDY DESIGN: Repeat measures design. OBJECTIVE: The purpose of this study was
      firstly, to describe a simple clinical tool that can be used to measure the
      extensibility of the flexor pollicis longus (FPL) muscle; secondly, to test its
      reliability; and thirdly, to attain some 'normative' data of the extensibility of
      the FPL muscle in a representative sample of people with tetraplegia. SETTING: A
      spinal cord injury unit in Sydney. SUBJECTS: A total of 37 people (62 hands) with
      C4-C7 tetraplegia. MAIN OUTCOME MEASURES: Angle of the carpometacarpal (CMC)
      joint of the thumb was measured in all subjects with the application of a series
      of thumb extensor torques. A device specifically designed for this purpose was
      used to standardize the torque and objectively quantify the CMC joint angle. In
      addition, repeat measurements were taken 3-5 days later in one subgroup of 13
      subjects (one hand per subject) and 3 months later in another subgroup of 13
      subjects (one hand per subject). ANALYSIS: Intraclass correlation coefficients
      and percent close agreement scores were derived to quantify the 3-5 days and 3
      month reliability between repeat measurements. RESULTS: The median CMC angle of
      the thumb with the application of a 0.044 Nm torque was 63 degrees (range, 20-93
      degrees). The intraclass correlation coefficients with the application of a 0.044
      Nm torque were 0.88 (95% CI, 0.65-0.96) for measurements taken 3-5 days apart,
      and 0.90 (95% CI, 0.67-0.97) for measurements taken 3 months apart. CONCLUSION:
      This study describes a simple and reliable way of measuring the extensibility of
      the FPL muscle in people with tetraplegia. This assessment tool and the
      'normative' data provided in this study can be used to further investigate the
      contribution of the passive mechanical properties of the FPL muscle to hand
      function of people with C6 and C7 tetraplegia.

PMID- 15867938
TI  - Amino-bisphosphonates in heterotopic ossification: first experience in five
      consecutive cases.
AB  - STUDY DESIGN: Retrospective, observational study in five consecutive cases.
      OBJECTIVES: The management of heterotopic ossification (HO), a frequent
      complication after spinal cord injury (SCI) and after orthopaedic surgery, is a
      therapeutic challenge with high recurrence rates of over 50%. Conflicting data
      were reported for Etidronate. The use of the more potent new generation of amino
      bisphosphonates has been put forward in different inflammatory, dysmorphogenic
      bone disease. In order to try and halt the underlying dysfunctional bone
      metabolism we have studied the action of pamidronate in five consecutive high
      risk patients with established HO of different etiology undergoing surgical
      removal. SETTING: University Hospital of Basel, Switzerland, Division of
      Endocrinology, Diabetology and Clinical Nutrition and the Department of
      Orthopedic Surgery. METHODS: In all five patients, ranging from 47 to 68 years of
      age, we used continuous pamidronate infusions perioperatively at a dosage of 120
      mg in the first 12 h and subsequent reduction to 75-60-30-15 mg/12 h over a
      period of 10-14 days. RESULTS: None of these patients showed clinical,
      radiographical and laboratory signs of HO recurrence or new forming HO in the
      follow-up 5-54 month after surgery. Potential side effects of high-dose
      bisphosphonate therapy such as osteoporosis and osteomalacia were not reported in
      any case. CONCLUSION: We postulate that pamidronate might have pronounced
      beneficial effects in high-risk patients with established HO undergoing excision
      surgery. Since the therapeutic window of amino-bisphosphonates has not yet been
      defined and the minimal necessary doses for preventing new HO are unknown,
      further studies are encouraged to confirm our findings and to identify the
      necessary dosage and duration of treatment and to pinpoint, which patients will
      benefit most from this treatment.

PMID- 15867939
TI  - Burkholderia pickettii spondylitis.
AB  - STUDY DESIGN: Case report describing Burkholderia pickettii spondylitis in a
      healthy adult. OBJECTIVES: To describe this very rare form of spondylitis and to
      discuss some of the difficulties in the diagnosis of B. pickettii spondylitis.
      SETTING: Department of Orthopaedic Surgery, Nayoro City General Hospital, Japan.
      METHODS: A 48-year-old woman presented with a complaint of severe back pain
      radiating from the right side of her chest. Plain radiographs of the spine showed
      osteolytic destruction of the right side of the T10 vertebral body at T10 level,
      with an involvement of the pedicle. Magnetic resonance image of the spine showed
      a low signal intensity from the T10 vertebral body on a Tl-weighted image and an
      increased signal intensity on T2-weighted sequence image. These lesions were
      enhanced when a contrast medium was used. The patient underwent open biopsy and
      specimens were collected through the right pedicle. RESULTS: Diagnosis was
      established on the basis of direct identification of the microorganism.
      Histological findings were consistent with examination of B. pickettii
      spondylitis. Chemotherapy (intravenous cefepime and per os minocycline) resulted
      in complete cure. CONCLUSION: B. pickettii is widely distributed in aqueous
      sources in nature and has not previously been considered to be an aggressive
      pathogen towards humans. This case report will help to improve our understanding
      of the ecology and virulent pathogenicity of this organism. A biopsy is an
      essential and reliable method for the early etiologic diagnosis, which will lead
      to prevent the development of more severe complications such as spinal cord
      compression.

PMID- 15867940
TI  - The A2 milk case: a critical review.
AB  - This review outlines a hypothesis that A1 one of the common variants of beta
      casein, a major protein in cows milk could facilitate the immunological processes
      that lead to type I diabetes (DM-I). It was subsequently suggested that A1 beta
      casein may also be a risk factor for coronary heart disease (CHD), based on
      between-country correlations of CHD mortality with estimated national consumption
      of A1 beta-casein in a selected number of developed countries. A company, A2
      Corporation was set up in New Zealand in the late 1990s to test cows and market
      milk in several countries with only the A2 variant of beta-casein, which appeared
      not to have the disadvantages of A1 beta-casein. The second part of this review
      is a critique of the A1/A2 hypothesis. For both DM-I and CHD, the between-country
      correlation method is shown to be unreliable and negated by recalculation with
      more countries and by prospective studies in individuals. The animal experiments
      with diabetes-prone rodents that supported the hypothesis about diabetes were not
      confirmed by larger, better standardised multicentre experiments. The single
      animal experiment supporting an A1 beta-casein and CHD link was small, short, in
      an unsuitable animal model and had other design weaknesses. The A1/A2 milk
      hypothesis was ingenious. If the scientific evidence had worked out it would have
      required huge adjustments in the world's dairy industries. This review concludes,
      however, that there is no convincing or even probable evidence that the A1 beta
      casein of cow milk has any adverse effect in humans. This review has been
      independent of examination of evidence related to A1 and A2 milk by the
      Australian and New Zealand food standard and food safety authorities, which have
      not published the evidence they have examined and the analysis of it. They stated
      in 2003 that no relationship has been established between A1 or A2 milk and
      diabetes, CHD or other diseases.

PMID- 15867941
TI  - Total energy expenditure (H218O), physical activity level and milk output of
      lactating rural Bangladeshi tea workers and nontea workers.
AB  - OBJECTIVE: To assess the total daily energy expenditure (TDEE), milk output and
      physical activity level (PAL) of chronically malnourished lactating women using
      the doubly labelled water method (DLW). DESIGN: Prospective, longitudinal study
      designed to assess the extent of malnutrition and energetics of lactating tea
      workers and nontea workers. SETTING: North-east Bangladesh on women working and
      living in the same tea estates. SUBJECTS: Of an original cohort of 150 lactating
      women, 30 were selected to participate in this study when they were at about 12
      months postpartum. One mother subsequently dropped out. INTERVENTIONS: On day 1
      each women provided a urine sample, was administered a dose of DLW and 6 h later
      provided another sample. Further urine samples were collected for 21 subsequent
      days. In addition, every 5 days the mother provided a milk sample and at the same
      time her baby provided a urine sample. RESULTS: Mean (s.d.) BMI was 17.4 (1.63).
      Mean TDEE and PAL were significantly higher in workers than nonworkers (8.42
      (1.38) and 6.83 (2.09) MJ/day, P = 0.02 and 1.92 (0.34) and 1.59 (0.44), P =
      0.03, respectively). Mean milk output was similar in the two groups (672 (180) ml
      and 749 (189) ml in workers and nonworkers, respectively). CONCLUSIONS: Based on
      international BMI cutoffs, 79% of mothers were suffering from some degree of
      chronic energy deficiency. A total of 35% of workers and 17% of nonworkers were
      engaged in strenuous physical activity. The mean milk output of both workers and
      nonworkers was not different and was high especially as most of the mothers were
      about 12 months postpartum. No relationship was found between menses return and
      any of the variables studied. SPONSORSHIP: World Health Organization, Nestle
      Foundation, UNICEF.

PMID- 15867942
TI  - Use of variety/diversity scores for diet quality measurement: relation with
      nutritional status of women in a rural area in Burkina Faso.
AB  - OBJECTIVES: To develop scores for food variety and diversity to assess the
      overall dietary quality in an African rural area; and to study their relationship
      with the nutritional status of women of childbearing age. DESIGN: Cross
      sectional. SETTING: Sahelian rural area in the North-East Burkina Faso (West
      Africa). SUBJECTS: A total of 691 mothers with children below the age of 5 y,
      selected at random in 30 villages. METHODS: A qualitative recall of women's food
      consumption during the previous 24 h made it possible to calculate a food variety
      score (FVS = count of food items consumed) and a dietary diversity score (DDS =
      count of food groups, among 14 groups). These scores were then divided into
      terciles. Body mass index (BMI), mid-upper arm circumference (MUAC) and body fat
      percentage (BFP) were used to determine the women's nutritional status. RESULTS:
      The overall dietary quality was poor: mean FVS (s.d.) = 8.3 (2.9) food items;
      mean DDS = 5.1 (1.7) food groups. A clear relationship was shown between both FVS
      and DDS (in terciles) and most nutritional indices. Women with a FVS in the
      lowest tercile had a mean BMI of 20.1, while those in the highest tercile had a
      BMI of 20.9 (P = 0.009). Those in the lowest tercile of DDS had a 22.8%
      prevalence of underweight vs 9.8% in the highest tercile (P < 0.0001). The latter
      relationship remained significant even when the subjects' sociodemographic and
      economic characteristics were accounted for. CONCLUSION: Dietary scores measured
      at the individual level are good proxies for overall dietary quality of women
      living in a poor rural African area. These scores were also shown to be linked
      with the nutritional status of women. FINANCING: IRD financed the study with the
      assistance of UNICEF for the purchase of anthropometric equipment. The first
      author received a research allowance from the French Ministry of Research through
      the doctoral school 393 of Pierre and Marie Curie University (Paris VI).

PMID- 15867944
TI  - Pharmacological profile and therapeutic potential of BM-573, a combined
      thromboxane receptor antagonist and synthase inhibitor.
AB  - BM-573 (N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl]urea), a
      torsemide derivative, is a novel non-carboxylic dual TXA2 synthase inhibitor and
      receptor antagonist. The pharmacological profile of the drug is characterized by
      a higher affinity for the thromboxane receptor than that of SQ-29548, one of the
      most powerful antagonists described to date, by a complete prevention of human
      platelet aggregation induced by arachidonic acid at a lower dose than either
      torsemide or sulotroban, and by a significantly prolonged closure time measured
      by the platelet function analyser (PFA-100). Moreover, at the concentrations of 1
      and 10 microM, BM-573 completely prevented production of TXB2 by human platelets
      activated by 0.6 mM of arachidonic acid. BM-573 prevents rat fundus contraction
      induced by U-46619 but not by prostacyclin or other prostaglandins. Despite
      possessing a chemical structure very similar to that of a diuretic torsemide, BM
      573 has no diuretic activity. BM-573 does not prolong bleeding time and, unlike
      some of the other sulfonylureas, has no effect on blood glucose levels. In vivo,
      BM-573 appears to have antiplatelet and antithrombotic activities since it
      reduced thrombus weight and prolonged the time to abdominal aorta occlusion
      induced by ferric chloride. BM-573 also relaxed rat aorta and guinea pig trachea
      precontracted with U-46619. In pigs, BM-573 completely antagonized pulmonary
      hypertensive effects of U-46619 and reduced the early phase of pulmonary
      hypertension in models of endotoxic shock and pulmonary embolism. Finally, BM-573
      protected pigs from myocardial infarction induced by coronary thrombosis. These
      results suggest that BM-573 should be viewed as a promising therapeutic agent in
      the treatment of pulmonary hypertension and syndromes associated with platelet
      activation.

PMID- 15867945
TI  - Colesevelam: potential uses for the newest bile resin.
AB  - Colesevelam is the newest bile resin with a unique chemical structure. It binds
      to bile acids with higher affinity than traditional bile acid sequestrants and
      has fewer gastrointestinal side effects and drug interactions. Colesevelam is
      safe and efficacious alone or in combination with HMG-CoA reductase inhibitors
      (statins) in reducing low-density lipoprotein cholesterol (LDL-C) levels. Despite
      this, the role of colesevelam in the treatment of hyperlipidemia remains limited,
      particularly in the face of new lipid lowering agents. As guidelines for
      cholesterol control become more stringent, the need to maximize therapeutic
      benefit through combination therapy will become increasingly more important.
      Colesevelam has a dose-sparing effect on statin therapy, potentially decreasing
      the risk of unwanted side effects or drug-drug interactions associated with
      statin use. This makes colesevelam a viable option for addition to a statin
      regimen when goal LDL-C levels cannot be achieved with a statin alone.
      Additionally, anecdotal reports indicate that colesevelam may have potential
      benefits in certain patient populations that cannot tolerate other lipid lowering
      therapies, including organ transplant recipients, cholestatic liver disesase, and
      end-stage renal disease. By recognizing the potential utility of colesevelam,
      clinicians can better manage those patients who are not able to tolerate first
      line therapies.

PMID- 15867946
TI  - The preclinical pharmacology of BIBN4096BS, a CGRP antagonist.
AB  - CGRP is an important neuropeptide found throughout the cardiovascular system.
      However, until recently it has been difficult to define its pharmacology or
      physiological role because of the lack of suitable antagonists. BIBN4096BS is a
      high-affinity, nonpeptide antagonist that shows much greater selectivity for
      human CGRP1 receptors compared to any other drug. Its pharmacology has been
      defined with studies on transfected cells or cell lines endogenously expressing
      receptors of known composition. These have allowed confirmation that in many
      human blood vessels, CGRP is working via CGRP1 receptors. However, it also
      interacts with other CGRP-activated receptors, of unknown composition. In vivo,
      clinical studies have shown that BIBN4096BS is likely to be useful in the
      treatment of migraine. It has also been used to define the role of CGRP in
      phenomena such as plasma extravasation and cardioprotection following ischemia.

PMID- 15867947
TI  - Bunazosin, a selective alpha1-adrenoceptor antagonist, as an anti-glaucoma drug:
      effects on ocular circulation and retinal neuronal damage.
AB  - Bunazosin hydrochloride is a potent and selective alpha1-adrenoceptor antagonist
      that has been clinically used both as a systemic antihypertensive as well as an
      ocular hypotensive drug. In a number of studies, we have examined some effects of
      bunazosin hydrochloride that might indicate its potential as an anti-glaucoma
      drug. In normal rabbit eyes, topically instilled bunazosin hydrochloride reached
      the posterior retina by local penetration at concentrations sufficient to
      attenuate the phenylephrine- or endothelin-1 (ET-1)-induced constriction of
      retinal arteries. Furthermore, bunazosin hydrochloride improved the impairment of
      optic nerve head (ONH) blood flow, the prolongation of visual-evoked potentials
      (VEP) implicit time, the enlargement of the optic disk cup, and the decrease in
      the number of retinal ganglion cell layer cells induced by repeated injections of
      ET-1 in rabbits. Topically instilled bunazosin hydrochloride improved the
      reductions in ONH capillary blood flow and VEP amplitude induced in rabbit eyes
      by nitric oxide synthase inhibition. In rat primary retinal cultures, bunazosin
      hydrochloride reduced glutamate-induced neuronal cell death, presumably through a
      Na+ channel blocking effect. In healthy humans, topically instilled bunazosin
      hydrochloride reportedly increases blood velocity in the ONH, retina and choroid,
      without significantly altering either blood pressure or heart rate. These results
      indicate that bunazosin hydrochloride exerts both an improvement effect within
      the ocular circulation and a direct neuroprotective effect. Hence, bunazosin
      hydrochloride may be useful as a therapeutic drug against ischemic retinal
      diseases (such as glaucoma and retinal vascular occlusive diseases) that are
      associated with disturbances of the ocular circulation.

PMID- 15867948
TI  - Efficacy and safety of sitosterol in the management of blood cholesterol levels.
AB  - Elevated levels of plasma LDL cholesterol (LDL-C) represent a major risk factor
      for cardiovascular disease. Treatments aimed at reducing levels of circulating
      LDL are regarded, therefore, as cardioprotective. The cholesterol lowering
      properties of plant sterols have been known for some time and many clinical
      studies have confirmed the efficacy of sitosterol in lowering plasma LDL-C
      concentrations. Animal studies have also shown reductions in LDL by sitosterol.
      The use of animal models has been useful in facilitating the elucidation of
      specific mechanisms by which this sterol exerts its hypocholesterolemic action.
      It is well known that plant sterols compete with cholesterol for space within
      bile salt micelles in the intestinal lumen thereby reducing cholesterol
      absorption. The understanding of the function of plant sterols in impeding
      cholesterol absorption has been clarified with the discovery of the adenosine
      binding cassette transporters, ABCG5/8, involved in the regulation of sterol
      absorption and secretion into the enterocyte and hepatocyte. Compared to
      cholesterol and other sterols, sitosterol is preferentially pumped out to the
      intestinal lumen by the ABCG5/8 transporters. This selective binding of
      sitosterol to the transporters ultimately results in significant lowering of
      plasma cholesterol. However, some findings support the hypothesis that plant
      sterols might be an additional risk factor for coronary heart disease. From the
      review of these studies, it is apparent that sitosterol is a useful dietary
      supplement for the lowering of plasma cholesterol. Nevertheless, this plant
      sterol should be used with caution in certain individuals who have a higher
      absorption rate of sitosterol.

PMID- 15867949
TI  - Pharmacological mechanisms contributing to the clinical efficacy of levosimendan.
AB  - Acute decompensation of chronic heart failure is a direct life-threatening
      situation with short-term mortality approaching 30%. A number of maladaptive
      changes are amplified within the cardiovascular system during the progression of
      chronic heart failure that makes the decompensation phase difficult to handle.
      Levosimendan is a new Ca2+-sensitizer for the treatment of acutely decompensated
      heart failure that has proved to be effective during the decompensation of
      chronic heart failure and acute myocardial infarction. Levosimendan differs from
      other cardiotonic agents that are used for acute heart failure in that it
      utilizes a unique dual mechanism of action: Ca2+-sensitization through binding to
      troponin C in the myocardium, and the opening of ATP-sensitive K+ channels in
      vascular smooth muscle. In general, these mechanisms evoke positive inotropy and
      vasodilation. Clinical studies suggested long-term benefits on mortality
      following short-term administration. It may, therefore, be inferred that
      levosimendan has additional effects on the cardiovascular system that are
      responsible for the prolongation of survival. Results of preclinical and clinical
      investigations suggest that the combination of levosimendan-induced cardiac and
      vascular changes has favorable effects on the coronary, pulmonary and peripheral
      circulations. Redistribution of the circulating blood offers an improved
      hemodynamic context for the development of a positive inotropic effect through
      Ca2+-sensitization of the contractile filaments, without a proportionate increase
      in myocardial oxygen consumption or the development of arrhythmias. Activation of
      ATP-sensitive K+ channels, both on sarcolemma and mitochondria, may protect
      against myocardial ischemia, and decreased levels of cytokines may prevent the
      development of further myocardial remodeling. Collectively, these effects of
      levosimendan shift the disturbed cardiovascular parameters towards normalization,
      thereby halting the perpetuation of the vicious cycle of heart failure
      progression. This may contribute to stabilization of the circulation and improved
      life expectancy of patients with chronic heart failure.

PMID- 15867950
TI  - Retigabine: chemical synthesis to clinical application.
AB  - Retigabine [D23129; N-(2-amino-4-(4-fluorobenzylamino)-phenyl)carbamic acid ethyl
      ester] is an antiepileptic drug with a recently described novel mechanism of
      action that involves opening of neuronal K(V)7.2-7.5 (formerly KCNQ2-5) voltage
      activated K(+) channels. These channels (primarily K(V)7.2/7.3) enable generation
      of the M-current, a subthreshold K(+) current that serves to stabilize the
      membrane potential and control neuronal excitability. In this regard, retigabine
      has been shown to have a broad-spectrum of activity in animal models of
      electrically-induced (amygdala-kindling, maximal electroshock) and chemically
      induced (pentylenetetrazole, picrotoxin, NMDA) epileptic seizures. These
      encouraging results suggest that retigabine may also prove useful in the
      treatment of other diseases associated with neuronal hyperexcitability.
      Neuropathic pain conditions are characterized by pathological changes in sensory
      pathways, which favor action potential generation and enhanced pain transmission.
      Although sometimes difficult to treat with conventional analgesics,
      antiepileptics can relieve some symptoms of neuropathic pain. A number of recent
      studies have reported that retigabine can relieve pain-like behaviors
      (hyperalgesia and allodynia) in animal models of neuropathic pain. Neuronal
      activation within several key structures within the CNS can also be observed in
      various animal models of anxiety. Moreover, amygdala-kindled rats, which have a
      lowered threshold for neuronal activation, also display enhanced anxiety-like
      responses. Retigabine dose-dependently reduces unconditioned anxiety-like
      behaviors when assessed in the mouse marble burying test and zero maze. Early
      clinical studies have indicated that retigabine is rapidly absorbed and
      distributed, and is resistant to first pass metabolism. Tolerability is good in
      humans when titrated up to its therapeutic dose range (600-1200 mg/day). No
      tolerance, dependence or withdrawal potential has been reported, although adverse
      effects can include mild dizziness, headache, nausea and somnolence. Thus,
      retigabine may prove to be useful in the treatment of a diverse range of disease
      states in which neuronal hyperexcitability is a common underlying factor.

PMID- 15867951
TI  - The pharmacology of DMP696 and DMP904, non-peptidergic CRF1 receptor antagonists.
AB  - CRF(1) antagonists DMP696 and DMP904 were designed as drug development candidates
      for the treatment of anxiety and depression. Both compounds display nanomolar
      affinity for human CRF(1) receptors, and exhibit >1000-fold selectivity for
      CRF(1) over CRF(2) receptors and over a broad panel of other proteins. DMP696 and
      DMP904 block CRF-stimulated adenylyl cyclase activity in cortical homogenates and
      cell-lines expressing CRF(1) receptors. Both compounds inhibit CRF-stimulated
      ACTH release from rat pituitary corticotropes. Binding and functional studies
      indicate that DMP696 and DMP904 behave as noncompetitive full antagonists. DMP696
      and DMP904 exhibit anxiolytic-like efficacy in several rat anxiety models. In the
      defensive withdrawal test, both compounds reduce exit latency with lowest
      effective doses of 3 and 1 mg/kg, respectively. The anxiolytic-like effect is
      maintained over 14 days of repeated dosing. In the context of a novel environment
      used in this test, DMP696 and DMP904 reverse mild stress-induced increases in
      plasma CORT secretion but at doses 3-4-fold greater than those required for
      anxiolyticlike efficacy. DMP696 and DMP904 are ineffective in three depression
      models including the learned helplessness paradigm at doses up to 30 mg/kg. At
      lowest anxiolytic-like doses, DMP696 and DMP904 occupy >50% CRF(1) receptors in
      the brain. The in vivo IC(50) values (plasma concentrations required for
      occupying 50% CRF(1) receptors) estimated based upon free, but not total, plasma
      concentrations are an excellent correlation with the in vitro IC(50) values.
      Neither compound produces sedation, ataxia, chlordiazepoxide-like subjective
      effects or adverse effects on cognition at doses 10-fold higher than anxiolytic
      like doses. Neither compound produces physiologically significant changes in
      cardiovascular, respiratory, gastrointestinal or renal functions at anxiolytic
      like doses. DMP696 and DMP904 have favorable pharmacokinetic profiles with good
      oral bioavailabilities. The overall pharmacological properties suggest that both
      compounds may be effective anxiolytics with low behavioral side effect
      liabilities.

PMID- 15867952
TI  - An overview of SSR149415, a selective nonpeptide vasopressin V(1b) receptor
      antagonist for the treatment of stress-related disorders.
AB  - Vasopressin (AVP) and corticotropin-releasing factor (CRF) are key mediators in
      the organism's neuro-adaptive response to stress. Through pituitary and central
      vasopressin V(1b) receptors, AVP participates in the control of the hypothalamic
      pituitary-adrenal axis (HPA) and is involved in various emotional processes.
      SSR149415 is the first selective, orally active vasopressin V(1b) receptor
      antagonist yet described. It is a competitive antagonist with nanomolar affinity
      for animal and human V(1b) receptors and displays a highly selective profile with
      regard to a large number of receptors or enzymes. In vitro, SSR149415 potently
      antagonizes functional cellular events associated with V(1b) receptor activation
      by AVP, such as intracellular Ca(2+) increase or proliferation in various cell
      systems. Pharmacological studies, performed by measuring ACTH secretion induced
      by various stimulants such as hormones (AVP or AVP + CRF) or physical stress
      (restraint or forced swimming stress and dehydration) in conscious rats or mice,
      confirm the antagonist profile of SSR149415 and its efficacy in normalizing ACTH
      secretion in vivo. SSR149415 is active by the oral route, at doses from 3 mg/kg,
      it potentiates CRF effect and displays a long-lasting oral effect in the
      different models. At 10 mg/kg p.o. its duration of action is longer than 4 h.
      This molecule also decreases anxiety and exerts marked antidepressant-like
      activity in several predictive animal models. The anxiolytic effects of SSR149415
      have been demonstrated in various Generalized Anxiety Disorders (GAD) models
      (four-plate, punished drinking, elevated plus-maze, light dark, mouse defense
      test battery, fear-potentiated startle and social interaction tests). It is as
      effective as the benzodiazepine diazepam in the acute stress exposure test.
      SSR149415 has similar efficacy to the reference antidepressant drug, fluoxetine,
      in acute (forced-swimming) and chronic (chronic mild stress and subordination
      stress) situations in rodents. SSR149415 also reduces offensive aggression in the
      resident-intruder model in mice and hamsters. Depending on the model, the minimal
      effective doses are in the range of 1-10 mg/kg i.p. or 3-10 mg/kg p.o. SSR149415
      is devoid of adverse effects on motor activity, sedation, memory or cognitive
      functions and produces no tachyphylaxis when administered repeatedly. It is well
      tolerated in animals and humans and exhibits an adequate ADME profile. Thus,
      SSR149415 is a new dual anxiolytic/antidepressant compound, which appears to be
      free of the known side effects of classical anxiolytic/antidepressant drugs.
      Clinical trials are in progress, they will hopefully demonstrate its
      therapeutical potential for treating stress-related disorders.

PMID- 15867953
TI  - Clinical data on the CGRP antagonist BIBN4096BS for treatment of migraine
      attacks.
AB  - Basal studies have shown that calcitonin gene-related peptide (CGRP) is a major
      sensory neuronal messenger in the trigeminovascular system, the pathway conveying
      intracranial pain. In migraine and cluster headache attacks, CGRP is released in
      parallel with the pain and successful treatment of the attacks abort both the
      associated pain and the CGRP release. The search for a potent small molecule CGRP
      antagonist has been successful and such an agent has been tested in preclinical
      and clinical studies. The aim of the present study was to examine current
      knowledge on the clinical pharmacology of systemic BIBN4096BS, which has been
      shown in man to abort acute migraine attacks as well or better than oral
      sumatriptan. BIBN4096BS is a specific and potent CGRP receptor antagonist in
      humans. In safety and tolerability studies the substance is well tolerated with
      no or only mild side effects. In acute migraine attacks the overall response was
      66% with the drug and 27% with placebo. A difference as compared to placebo was
      seen at 30 min; the response was still rising at 4 h suggesting a long duration
      of action. At 24 h the pain-free rate was better than that with triptans,
      suggesting a lower grade of rebound and perhaps even a prophylactic possibility.

PMID- 15867954
TI  - LY503430: pharmacology, pharmacokinetics, and effects in rodent models of
      Parkinson's disease.
AB  - Glutamate is the major excitatory transmitter in the brain. Recent developments
      in the molecular biology and pharmacology of the alpha-amino-3-hydroxy-5
      methylisoxazole-4-propionic acid (AMPA)-subtype of glutamate receptors have led
      to the discovery of selective, potent and systemically active AMPA receptor
      potentiators. These molecules enhance synaptic transmission and play important
      roles in plasticity and cognitive processes. In the present studies we
      characterized a novel AMPA receptor potentiator, LY503430, on recombinant human
      GLU(A1-4) and native preparations in vitro, and then evaluated the potential
      neuroprotective effects of the molecule in rodent models of Parkinson's disease.
      Results indicated that at submicromolar concentrations LY503430 selectively
      enhanced glutamate-induced calcium influx into HEK293 cells transfected with
      human GLU(A1), GLU(A2), GLU(A3), or GLU(A4) AMPA receptors. The molecule also
      potentiated AMPA-mediated responses in native cortical, hippocampal and
      substantia nigra neurones. LY503430 had good oral bioavailability in both rats
      and dogs. We also report here that LY503430 provided dose-dependent functional
      and histological protection in animal models of Parkinson's disease. The
      neurotoxicity following unilateral infusion of 6-hyrdoxydopamine (6-OHDA) into
      either the substantia nigra or the striatum of rats and that following systemic 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice were reduced.
      Interestingly, LY503430 also had neurotrophic actions on functional and
      histological outcomes when treatment was delayed until well after (6 or 14 days)
      the lesion was established. LY503430 also produced some increase in brain derived
      neurotrophic factor (BDNF) in the substantia nigra and a dose-dependent increase
      in growth associated protein-43 (GAP-43) expression in the striatum. Therefore,
      we propose that AMPA receptor potentiators such as LY503430 offer the potential
      of a new disease modifying therapy for Parkinson's disease.

PMID- 15867955
TI  - Immune response in cervical dysplasia induced by human papillomavirus: the
      influence of human immunodeficiency virus-1 co-infection -- review.
AB  - Human immunodeficiency virus (HIV-1) has become an important risk factor for
      human papillomavirus (HPV) infection and the development of HPV associated
      lesions in the female genital tract. HIV-1 may also increase the oncogenicity of
      high risk HPV types and the activation of low risk types. The Center for Disease
      Control and Prevention declared invasive cervical cancer an acquired
      immunodeficiency virus (AIDS) defining illness in HIV positive women.
      Furthermore, cervical cancer happens to be the second most common female cancer
      worldwide. The host's local immune response plays a critical factor in
      controlling these conditions, as well as in changes in the number of professional
      antigen-presenting cells, cytokine, and MHC molecules expression. Also, the
      production of cytokines may determine which arm of the immune response will be
      stimulated and may influence the magnitude of immune protection. Although there
      are many studies describing the inflammatory response in HPV infection, few data
      are available to demonstrate the influence of the HIV infection and several
      questions regarding the cervical immune response are still unknown. In this
      review we present a brief account of the current understanding of HIV/HPV co
      infection, emphasizing cervical immune response.

PMID- 15867956
TI  - Prevalence of hepatitis-B surface antigen among blood donors and human
      immunodeficiency virus-infected patients in Jos, Nigeria.
AB  - Information is very scarce on the prevalence of hepatitis-B virus (HBV) infection
      among blood donors and patients with human immunodeficiency virus (HIV) infection
      in Nigeria. Hepatitis-B surface antigen (HBsAg) ELISA was used to determined the
      prevalence of HBsAg among 175 blood donors (aged 20-40 years) and 490 HIV
      infected patients (aged 17-60 years) in Jos, Nigeria. Twenty-five (14.3%) of the
      blood donors and 127 (25.9%) of the HIV-infected individuals were HBsAg
      seropositive, indicating a higher HBV infection among HIV-infected persons than
      among healthy blood donors. A slightly higher HBsAg seroprevalence was recorded
      in the males (14.6%) than females (12.9%) of the blood donors. Among the HIV
      infected patients, the males had considerably higher HBsAg seroprevalence than
      the females (31.8 vs 22.1%) with the highest prevalence of HBsAg occurring in the
      51-60 years age group (44%), followed by those of 31-40 years (28.2%). Results
      confirmed the high endemicity of HBV infection in Jos, Nigeria and the
      significantly greater prevalence of HBV infection among HIV-infected patients
      than among blood donors.

PMID- 15867957
TI  - First record of human trichinosis in Chile associated with consumption of wild
      boar (Sus scrofa).
AB  - The first South American case of human trichinosis, resulting from the
      consumption of roast wild boar (Sus scrofa) is reported in Chile. The patient
      presented fever, diarrhea, myalgias, facial edema, sub-conjunctival reddening,
      photophobia, eosinophilia, and elevated glutamic oxalacetic transaminase. The
      diagnosis was confirmed by two immunoenzymatic tests (ELISA) using somatic and
      excretion-secretion antigens.

PMID- 15867958
TI  - Biomphalaria tenagophila: dominant character of the resistance to Schistosoma
      mansoni in descendants of crossbreedings between resistant (Taim, RS) and
      susceptible (Joinville, SC) strains.
AB  - The aim of the present work was to study parasitological, molecular, and genetic
      aspects in descendants of crossbreedings between a totally resistant Biomphalaria
      tenagophila strain (Taim, RS) and another one highly susceptible (Joinville, SC)
      to Schistosoma mansoni. Descendants F1 and F2 were submitted to S. mansoni
      infection (LE strain). The susceptibility rates for individuals from Group F1
      were 0 to 0.6%, and from Group F2 was 7.2%. The susceptible individuals from
      Group F2 discharged a lower number of cercariae, when compared with the
      susceptible parental group, and in 2 out of 9 positive snails the cercarial
      elimination was discontinued. In order to identify genetic markers associated
      with resistance the genotype of parental snails and their offspring F1 and F2
      were analyzed by means of the randomly amplified polymorphic DNA method.
      Nevertheless, it was not possible to detect any marker associated to resistance,
      but the results showed that in the mentioned species the resistance character is
      determined by two dominant genes.

PMID- 15867959
TI  - Bat flies (Diptera: Streblidae, Nycteribiidae) parasitic on bats (Mammalia:
      Chiroptera) at Parque Estadual da Cantareira, Sao Paulo, Brazil: parasitism rates
      and host-parasite associations.
AB  - A total of 443 bat flies belonging to the families Nycteribiidae and Strelidae,
      were collected on 22 species of bats (Molossidae, Phyllostomidae, and
      Vespertilionidae) from Parque Estadual da Cantareira (Sao Paulo, Brazil), between
      January, 2000 and January, 2001. Eighteen new occurrences of bat flies were
      recorded on Anoura geoffroyi (Anastrebla caudiferae), Glossophaga soricina (A.
      caudiferae), Sturnira lilium (Trichobius phyllostomae, T. furmani, and
      Paraeuctenodes similis), Artibeus lituratus (A. caudiferae), A. fimbriatus
      (Megistopoda proxima), A. obscurus (Metelasmus pseudopterus), Myotis nigricans
      (M. proxima, M. aranea, Paratrichobius longicrus), M. ruber (Anatrichobius
      passosi, Joblingia sp.), M. levis (A. passosi), M. albescens (A. passosi, Basilia
      andersoni), and Histiotus velatus (M. aranea). Seven new occurrences were
      recorded for the state of Sao Paulo, increasing the range for T. tiptoni, T.
      furmani, M. proxima, Aspidoptera falcata, A. caudiferae, A. modestini and B.
      andersoni. The relationships between parasitism and host sex, reproductive stage,
      age hyperparasitism by fungi are discussed.

PMID- 15867960
TI  - Programmed cell death in Trypanosoma cruzi induced by Bothrops jararaca venom.
AB  - Cells die through a programmed process or accidental death, know as apoptosis or
      necrosis, respectively. Bothrops jararaca is a snake whose venom inhibits the
      growth of Trypanosoma cruzi epimastigote forms causing mitochondrion swelling and
      cell death. The aim of the present work was to determine the type of death
      induced in epimastigotes of T. cruzi by this venom. Parasite growth was inhibited
      after venom treatment, and 50% growth inhibition was obtained with 10 microg/ml.
      Ultrastructural observations confirmed mitochondrion swelling and kinetoplast
      disorganization. Furthermore, cytoplasmic condensation, loss of mitochondrion
      membrane potential, time-dependent increase in phosphatidylserine exposure at the
      outer leaflet plasma membrane followed by permeabilization, activation of caspase
      like protein and DNA fragmentation were observed in epimastigotes throughout a 24
      h period of venom treatment. Taken together, these results indicate that the
      stress induced in epimastigote by this venom, triggers a programmed cell death
      process, similar to metazoan apoptosis, which leads to parasite death.

PMID- 15867961
TI  - Moonlight and blood-feeding behaviour of Lutzomyia intermedia and Lutzomyia
      whitmani (Diptera:Psychodidae:Phlebotominae), vectors of American cutaneous
      leishmaniasis in Brazil.
AB  - Lutzomyia intermedia (Lutz & Neiva, 1912) and L. whitmani (Antunes & Coutinho,
      1939) (Diptera: Psychodidae: Phlebotominae), two important vectors of American
      cutaneous leishmaniasis in Brazil, occur in sympatry in the locality of Posse
      county, Petropolis municipality, state of Rio de Janeiro, Brazil. We investigated
      the influence of the lunar cycle on the frequency of specimens of the two species
      caught while attempting to bite the collectors and in CDC light traps. Analysis
      of the numbers of sand flies captured in different lunar phases for two
      consecutive years in the peridomestic site and forest shows that there is a
      significant positive correlation between moonlight intensity and the numbers of
      L. intermedia and L. whitmani females collected while blood-feeding, whereas the
      opposite was observed for the CDC traps.

PMID- 15867962
TI  - Multiplex-PCR for detection of natural Leishmania infection in Lutzomyia spp.
      captured in an endemic region for cutaneous leishmaniasis in state of Sucre,
      Venezuela.
AB  - We studied the natural infection of Lutzomyia (Lutzomyia) sp. with Leishmania in
      endemic foci of cutaneous leishmaniasis in the Paria peninsula, state of Sucre,
      Venezuela. Sand flies were collected between March 2001 and June 2003, using
      Shannon light-traps and human bait. Of the 1291 insects captured, only two
      species of phlebotomines were identified: L. ovallesi (82.75%) and L. gomezi
      (17.42%). A sample of the collected sand flies (51 pools of 2-12 individuals)
      were analyzed by using a multiplex-PCR assay for simultaneous detection of New
      Word Leishmaniaand Viannia subgenera. The results showed a total of 8 pools
      (15.68%) infected; of these, 7 were L. ovallesi naturally infected with L.
      braziliensis (2 pools) and L. mexicana (5 pools) and 1 pool of L. gomezi infected
      by L. braziliensis.

PMID- 15867964
TI  - A new Culicoides (Diptera:Ceratopogonidae) of the subgenus Diphaomyia from Peru.
AB  - A new species of Culicoides of the subgenus Diphaomyia, Culicoides jurbergi
      Felippe-Bauer, is described and illustrated based on female specimens collected
      biting man and with light traps in Peruvian Amazonia. The species is compared
      with its similar congener mirsae Ortiz.

PMID- 15867963
TI  - Genetic polymorphism of the serine rich antigen N-terminal region in Plasmodium
      falciparum field isolates from Brazil.
AB  - In this work we investigated the frequency of polymorphism in exon II of the gene
      encoding most of the amino-terminal region of the serine rich antigen (SERA) in
      Plasmodium falciparum field samples. The blood samples were collected from P.
      falciparum infected individuals in three areas of the Brazilian Amazon. Two
      fragments have been characterized by polymerase chain reaction: one of 175 bp
      corresponding to the repeat region with 5 octamer units and one other of 199 bp
      related to the 6 repeat octamer units of SERA protein. The 199 bp fragment was
      the predominant one in all the studied areas. The higher frequency of this
      fragment has not been described before and could be explained by an immunological
      selection of the plasmodial population in the infected individuals under study.
      Since repeat motifs in the amino-terminal region of SERA contain epitopes
      recognized by parasite-inhibitor antibodies, data reported here suggest that the
      analysis of the polymorphism of P. falciparum isolates in different geographical
      areas is a preliminary stage before the final drawing of an universal vaccine
      against malaria can be reached.

PMID- 15867965
TI  - Antifungal activity from Ocimum gratissimum L. towards Cryptococcus neoformans.
AB  - Cryptococcal infection had an increased incidence in last years due to the
      explosion of acquired immune deficiency syndrome epidemic and by using new and
      effective immunosuppressive agents. The currently antifungal therapies used such
      as amphotericin B, fluconazole, and itraconazole have certain limitations due to
      side effects and emergence of resistant strains. So, a permanent search to find
      new drugs for cryptococcosis treatment is essential. Ocimum gratissimum, plant
      known as alfavaca (Labiatae family), has been reported earlier with in vitro
      activity against some bacteria and dermatophytes. In our work, we study the in
      vitro activity of the ethanolic crude extract, ethyl acetate, hexane, and
      chloroformic fractions, essential oil, and eugenol of O. gratissimum using an
      agar dilution susceptibility method towards 25 isolates of Cryptococcus
      neoformans. All the extracts of O. gratissimum studied showed activity in vitro
      towards C. neoformans. Based on the minimal inhibitory concentration values the
      most significant results were obtained with chloroformic fraction and eugenol. It
      was observed that chloroformic fraction inhibited 23 isolates (92%) of C.
      neoformans at a concentration of 62.5 microg/ml and eugenol inhibited 4 isolates
      (16%) at a concentration of 0.9 microg/ml. This screening may be the basis for
      the study of O. gratissimum as a possible antifungal agent.

PMID- 15867966
TI  - Biological effect of 1-dodecanol in teneral and post-teneral Rhodnius prolixus
      and Triatoma infestans (Hemiptera: Reduviidae).
AB  - Topical application of 1-dodecanol was significantly more toxic against teneral
      first nymphs (1-3 h old) than post-teneral first nymphs (24 h old). The lethal
      dose ratios were 711,500 for Rhodnius prolixus and 3613 for Triatoma infestans.
      No significative difference between LD50 was found when 1-dodecanol was injected
      in recently hatched adult R. prolixus (1-4 h old) nor in older adults (24 h old).
      These values were similar to those calculated for deltamethrin (an effective
      triatomicide), showing that 1-dodecanol had no insecticidal properties when it
      was applied by injection. Topical application of high dose of 1-dodecanol (1
      microg/i) on teneral first nymphs of R. prolixus, produced an interruption of the
      darkening process of the cuticle, and probably in the development of its
      physiological properties.

PMID- 15867967
TI  - Report of the Fifth Brazilian Symposium on HIV/AIDS Research. Rio de Janeiro, RJ,
      Brazil. November 23-26, 2003.

PMID- 15867968
TI  - Human immunodeficiency virus type 1 (HIV-1) genotyping in Rio de Janeiro, Brazil:
      assessing subtype and drug-resistance associated mutations in HIV-1 infected
      individuals failing highly active antiretroviral therapy.
AB  - In order to assess the human immunodeficiency virus type 1 (HIV-1) drug
      resistance mutation profiles and evaluate the distribution of the genetic
      subtypes in the state of Rio de Janeiro, Brazil, blood samples from 547 HIV-1
      infected patients failing antiretroviral (ARV) therapy, were collected during the
      years 2002 and 2003 to perform the viral resistance genotyping at the Renageno
      Laboratory from Rio de Janeiro (Oswaldo Cruz Foundation). Viral resistance
      genotyping was performed using ViroSeq Genotyping System (Celera Diagnostic
      Abbott, US). The HIV-1 subtyping based on polymerase (pol) gene sequences
      (protease and reverse transcriptase-RT regions) was as follows: subtype B
      (91.2%), subtype F (4.9%), and B/F viral recombinant forms (3.3%). The subtype C
      was identified in two patients (0.4%) and the recombinant CRF_02/AG virus was
      found infecting one patient (0.2%). The HIV-1 genotyping profile associated to
      the reverse transcriptase inhibitors has shown a high frequency of the M184V
      mutation followed by the timidine-associated mutations. The K103N mutation was
      the most prevalent to the non-nucleoside RT inhibitor and the resistance
      associated to protease inhibitor showed the minor mutations L63P, L10F/R, and
      A71V as the more prevalent. A large proportion of subtype B was observed in HIV-1
      treated patients from Rio de Janeiro. In addition, we have identified the
      circulation of drug-resistant HIV-1 subtype C and are presenting the first report
      of the occurrence of an African recombinant CRF_02/AG virus in Rio de Janeiro,
      Brazil. A clear association between HIV-1 subtypes and protease resistance
      mutations was observed in this study. The maintenance of resistance genotyping
      programs for HIV-1 failing patients is important to the management of ARV
      therapies and to attempt and monitor the HIV-1 subtype prevalence in Brazil.

PMID- 15867969
TI  - The human immunodeficiency virus preventive vaccine research at the French
      National Agency for acquired immunodeficiency syndrome research.
AB  - The human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)
      epidemic is of unprecedented gravity and is spreading rapidly, notably in the
      most disadvantaged regions of the world. The search for a preventive vaccine is
      thus an absolute priority. For over 10 years the French National Agency for AIDS
      research (ANRS) has been committed to an original program combining basic science
      and clinical research. The HIV preventive vaccine research program run by the
      ANRS covers upstream research for the definition of immunogens, animal models,
      and clinical research to evaluate candidate vaccines. Most researchers in 2004
      believe that it should be possible to obtain partial vaccine protection through
      the induction of a strong and multiepitopic cellular response. Since 1992, the
      ANRS has set up 15 phases I and II clinical trials in order to evaluate the
      safety and the capacity of the candidate vaccines for inducing cellular immune
      responses. The tested candidate vaccines were increasingly complex recombinant
      canarypox viruses (Alvac) containing sequences coding for certain viral proteins,
      utilized alone or combined with other immunogens (whole or truncated envelope
      proteins). ANRS has also been developing an original strategy based on the
      utilization of lipopeptides. These comprise synthetic fragments of viral proteins
      associated with lipids that facilitate the induction of a cellular immune
      response. These approaches promptly allowed the assessment of a prime-boost
      strategy combining a viral vector and lipopeptides.

PMID- 15867970
TI  - Human immunodeficiency virus type 1 neutralization by plasma from B or F genotype
      infected individuals.
AB  - Anti-human immunodeficiency virus type 1 (HIV-1) "binding antibodies" (antibodies
      capable of binding to synthetic peptides or proteins) occur throughout HIV-1
      infection, are high-titered and highly cross-reactive, as confirmed in this study
      by analyzing plasma from B and F genotype HIV-1 infected individuals. Plasma from
      individuals infected with clade F HIV-1 displayed the most frequent cross
      reactivity, in high titers, while Bbr plasma showed much higher specificity.
      Similarly, neutralization of a reference HIV-1 isolate (HIV-1 MN) was more
      frequently observed by plasma from F than B genotype infected individuals. No
      significant difference was seen in neutralization susceptibility of primary B,
      Bbr or F clade HIV-1 by plasma from individuals infected with the classical B
      (GPGR) or F HIV-1, but Bbr (GWGR) plasma were less likely to neutralize the F
      genotype primary HIV-1 isolates. The data indicate that both B and F genotype
      derived vaccines would be equally effective against B and F HIV-1 infection, with
      a slightly more probable effectiveness for F than B genotype. Although the Bbr
      variant appears to induce a much more specific humoral immune response, the
      susceptibility in neutralizing the Brazilian HIV-1 B genotype Bbr variant is
      similar to that observed with the classical B genotype HIV-1.

PMID- 15867971
TI  - Is human immunodeficiency virus/acquired immunodeficiency syndrome decreasing
      among Brazilian injection drug users? Recent findings and how to interpret them.
AB  - We briefly review findings from Brazilian settings where the human
      immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic
      among injection drug users (IDUs) seems to be decreasing, highlighting recent
      findings from Rio de Janeiro and discussing methodological alternatives. Former
      analyses using serologic testing algorithm for recent HIV seroconversion have
      shown that HIV incidence has been low in IDUs recruited by two different surveys
      carried out in Rio, where low injection frequencies and infection rates have been
      found among new injectors. The proportion of AIDS cases among IDUs in Rio has
      been fairly modest, compared to Sao Paulo and especially to the southernmost
      states. Notwithstanding, the interpretation of findings from serial surveys
      constitutes a challenge, magnified in the assessment of HIV spread among IDUs due
      to the dynamic nature of the drug scenes and limitations of sampling strategies
      targeting hard-to-reach populations. Assessment of epidemic trends may profit
      from the triangulation of data, but cannot avert biases associated with sampling
      errors. Efforts should be made to triangulate data from different sources,
      besides exploring specific studies from different perspectives. In an attempt to
      further assess the observed trends, we carried out original analyses using data
      from Brazilian AIDS databank.

PMID- 15867972
TI  - Antiretroviral resistance mutations in human immunodeficiency virus type 1
      infected patients enrolled in genotype testing at the Central Public Health
      Laboratory, Sao Paulo, Brazil: preliminary results.
AB  - Antiretroviral resistance mutations (ARM) are one of the major obstacles for
      pharmacological human immunodeficiency virus (HIV) suppression. Plasma HIV-1 RNA
      from 306 patients on antiretroviral therapy with virological failure was
      analyzed, most of them (60%) exposed to three or more regimens, and 28% of them
      have started therapy before 1997. The most common regimens in use at the time of
      genotype testing were AZT/3TC/nelfinavir, 3TC/D4T/nelfinavir and
      AZT/3TC/efavirenz. The majority of ARM occurred at protease (PR) gene at residue
      L90 (41%) and V82 (25%); at reverse transcriptase (RT) gene, mutations at residue
      M184 (V/I) were observed in 64%. One or more thymidine analogue mutations were
      detected in 73%. The number of ARM at PR gene increased from a mean of four
      mutations per patient who showed virological failure at the first ARV regimens to
      six mutations per patient exposed to six or more regimens; similar trend in RT
      was also observed. No differences in ARM at principal codon to the three drug
      classes for HIV-1 clades B or F were observed, but some polymorphisms in
      secondary codons showed significant differences. Strategies to improve the cost
      effectiveness of drug therapy and to optimize the sequencing and the rescue
      therapy are the major health priorities.

PMID- 15867974
TI  - Effect of cannabis use in human brain activity.

PMID- 15867975
TI  - [Cannabis: what is the extent of its harmful effects?].

PMID- 15867976
TI  - Addiction's research in developing countries: adjusting abounding questions to
      limited resources.

PMID- 15867977
TI  - [Psychiatry residency in Brazil: a contribution to the debate].

PMID- 15867978
TI  - Secondary tics and tourettism.
AB  - Motor and phonic tics are most frequently due to Tourette syndrome, but there are
      many other causes of tics. We analyzed data on 155 patients with tics and co
      existent disorders (101M/54F; mean age 40.5 +/- 20.2 years). Fourteen (9.0%)
      patients had tics associated with an insult to the basal ganglia, such as head
      trauma (N = 4, 2.5%), stroke (N = 2, 1.2%), encephalitis (N = 3, 1.9%) and other
      causes. In addition, certain drugs, toxins, and post-infectious causes were
      associated with tics. Rarely, peripheral injury can cause movement disorders,
      including tics (N = 1, 0.6%). Pervasive developmental disorders, including
      Asperger's syndrome (N = 13, 8.3%), mental retardation (N = 4, 2.5%), autism (N =
      3, 1.9%), and Savant's syndrome (N = 1, 0.6%), also may be associated with tics,
      as noted in 21 of the 155 patients (13.5%). Genetic and chromosomal disorders,
      such as Down's syndrome 5 (3.2%), neuroacanthocytosis (N = 2, 1.2%), and
      Huntington's disease (N = 1, 0.6%), were associated with tics in 16 patients
      (10.3%). We have also examined the co-existence of tics and other movement
      disorders such as dystonia (N = 31, 20.0%) and essential tremor (N = 17, 10.9%).
      Sixteen (10.3%) patients presented psychogenic tics, and one (0.6%) psychogenic
      tics and dystonia; conversely, Tourette syndrome preceded the onset of
      psychogenic dystonia (N = 1, 0.6%), and psychogenic tremor (N = 1, 0.6%) in two
      patients. Finally, 12 (7.7%) patients had tics in association with non-movement
      related neurological disorders, such as static encephalopathy (N = 2, 1.2%) and
      seizures (N = 3, 1.9%). To understand the physiopathology of tics and Tourette
      syndrome, it is important to recognize that these may be caused or associated
      with other disorders.

PMID- 15867979
TI  - The efficacy of antidepressants for generalized anxiety disorder: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To investigate the efficacy and acceptability of antidepressants in
      the treatment of generalized anxiety disorder. METHODS: All randomized controlled
      trials assessing the use of antidepressants in generalized anxiety disorder up to
      may 2002 were included. Non randomized trials and those that included patients
      with both generalized anxiety disorder and another Axis I co-morbidity were
      excluded. Relative risks, weighted mean difference and number needed to treat
      were estimated. People who died or dropped out were regarded as having had no
      improvement. RESULTS: Antidepressants (imipramine, venlafaxine and paroxetine)
      were found to be superior to placebo in treating generalized anxiety disorder.
      The calculated number needed to treat for antidepressants in generalized anxiety
      disorder was 5.15. Dropout rates did not differ between antidepressants and
      placebo. CONCLUSION: The available evidence suggests that antidepressants would
      probably be a reasonable treatment for generalized anxiety disorder patients in
      the clinical context.

PMID- 15867980
TI  - The Eating Disorders Section of the Development and Well-Being Assessment
      (DAWBA): development and validation.
AB  - OBJECTIVE: Development and validation of the Eating Disorders Section of the
      Development and Well-Being Assessment (DAWBA). It is a package of questionnaires,
      interviews and evaluation techniques, designed to generate DSM-IV and ICD-10
      based diagnoses of anorexia, bulimia nervosa and the respective partial syndromes
      in epidemiological studies, in subjects who are 7 to 17 years old. The parents
      are interviewed in all cases, as are young people aged 11 or more. METHODS: 174
      girls, divided into three groups, were assessed with the Eating Disorders Section
      of the Development and Well-Being Assessment: 48 with eating disorders, 55
      clinical controls (with depression, obsessive-compulsive disorder or
      gastrointestinal disease) and 71 community controls. The sensitivity, specificity
      and predictive values of the assessment were investigated by comparing the
      Development and Well-Being Assessment diagnoses with independent psychiatric
      diagnoses. The test-retest reliability was investigated by reapplying the measure
      on 55 subjects after 2 or 3 weeks. RESULTS: For the detection of any DSM-IV and
      ICD-10 eating disorder, the final Development and Well-Being Assessment diagnosis
      had a sensitivity of 100%, specificity of 94%, positive predictive value of 88%,
      and a negative predictive value of 100%; there was 95% agreement between the
      initial and repeat diagnoses (a kappa of 0.81). CONCLUSION: The Eating Disorders
      Section of the Development and Well-Being Assessment has suitable psychometric
      properties for use in clinical and epidemiological studies.

PMID- 15867981
TI  - Early-onset social anxiety disorder in adults: clinical and therapeutic features.
AB  - OBJECTIVE: To investigate possible differences in clinical and treatment response
      in patients suffering from early-onset (< 18 years) and late-onset (> or =18
      years) social anxiety disorder. METHODS: Patients diagnosed with social anxiety
      disorder of early-onset (n = 47; 75.8%) were compared to those diagnosed with
      late-onset social anxiety disorder (n = 15; 24.2%) in terms of age, mode of
      onset, subtype, psychiatric comorbidities (according to the Structured Clinical
      Interview for DSM-IV), symptom severity and response (assessed according to the
      Clinical Global Impression scale) after at least ten weeks of drug treatment. The
      statistical analyses included chi2 tests with Yates correction or Fisher's exact
      test, as well as Student's t-test or Mann-Whitney test. The level of statistic
      significance adopted was 5%. RESULTS: Patients presenting early-onset phobic
      symptoms more frequently: were inactive (chi2 = 4.28; df = 1; p = 0.04); suffered
      from the generalized subtype of social phobia (chi2 = 6.53; df = 1; p = 0.01);
      and presented psychiatric comorbidity (chi2 = 6.71; df = 1; p = 0.01). No
      differences were observed between the groups in severity of symptoms and
      therapeutic response. CONCLUSION: The findings suggest the existence of a
      possible social anxiety disorder subtype characterized by early onset of
      symptoms, higher rates of absenteeism, a wider range of social phobia symptoms
      and psychiatric complications.

PMID- 15867982
TI  - Habits, attitudes and beliefs of smokers in four Brazilian capitals.
AB  - Tobacco consumption is a major cause of death and disease, and quitting smoking
      is the most important thing smokers can do to benefit their health. As of the
      last census, 32.5% of the Brazilian population smoked, but little is known about
      how many wish to quit and which factors can influence them to make such a
      decision. OBJECTIVE: To analyze the habits, attitudes and believes of smokers in
      four major Brazilian cities and compare the results with data from 17 European
      countries. METHODS: A total of 800 smokers were interviewed. The interviews were
      conducted in person and individually, using a semi-structured questionnaire.
      Smokers were defined as individuals who smoke at least one cigarette per week.
      They were recruited by intentional sampling (confronted on the street and invited
      to answer the questionnaire) according to pre-established quotas based on social
      class, gender, occupation and age. Therefore, the number of interviews in a
      certain population stratum within the sample was determined according to the
      proportion of smokers generally represented by that stratum. RESULTS: The
      majority of smokers interviewed presented a low to moderate degree of dependence
      and wanted to stop smoking. The greater was the motivation to quit, the higher
      was the number of quitting attempts, as well as the probability of having
      received medical advice. Only 21% of the smokers had been advised to stop smoking
      by their doctors. The factor cited by smokers as the one that would most
      influence their future efforts to stop was "concern about exposing children,
      relatives and friends to tobacco smoke". The population of Brazil, in contrast to
      those of European countries, seems to have a high degree of consciousness
      regarding the fight against tobacco.

PMID- 15867983
TI  - Suicidal behavior in the community: prevalence and factors associated with
      suicidal ideation.
AB  - OBJECTIVES: To estimate the life prevalence rates of suicidal ideation, suicidal
      plans and suicide attempts and verify factors associated to suicidal ideation.
      METHODS: 515 individuals > or = 14 years old were selected at random (cluster and
      stratified sample) and assessed by means of the WHO SUPRE-MISS interview, SRQ-20
      and AUDIT. Life prevalence rates were estimated. Uni and multivariate analyses
      were performed. Odds ratios, together with confidence intervals, were adjusted by
      gender and age. RESULTS: Life prevalence rates were 17.1% (95% CI: 12.9 - 21.2)
      for suicidal ideation, 4.8% (95% CI: 2.8 - 6.8) for plans and 2.8% (95% CI: 0.09 
      4.6) for suicide attempts. Only one-third of those who attempted suicide were
      later treated at a health facility. The 12-month prevalence rates were,
      respectively, 5.3% (95% CI: 3.5 - 7.2), 1.9% (95% CI: 1.0 - 2.8) and 0.4% (95%
      CI: -0.3 - 1.1). Suicidal ideation was more frequently reported by women (OR =
      1.7), young adults (20-29 years old: OR = 2.9; 30-39 years old: OR = 3.6,
      compared to the 14-19 year old group), those living alone (OR = 4.2) and those
      presenting mental disorders (OR between 2.8 and 3.8). CONCLUSION: The prevalence
      of suicidal behavior was similar to that found in most studies carried out in
      other countries. Suicidal ideation was consistently associated with factors
      related to mental disorders or psychological distress. This should be taken into
      account when developing strategies to prevent suicidal behavior.

PMID- 15867984
TI  - Validity of the CAGE questionnaire for screening alcohol-dependent inpatients on
      hospital wards.
AB  - OBJECTIVE: To verify the validity of the CAGE questionnaire in screening
      inpatients with alcohol dependence. METHODS: In a transversal study, 747 medical
      inpatients hospitalized on general medical wards in the Federal University of
      Santa Catarina University Hospital were evaluated. Sociodemographic and clinical
      data were collected and the following instruments were used: the CAGE
      questionnaire and the Mini International Neuropsychiatry Interview (MINI), the
      latter being a semi-structured interview used as the gold standard for diagnosing
      alcohol dependence (according to DSM-IV criteria). Validity indices (sensitivity
      and specificity) were assessed for the different possible CAGE cut-off points.
      The ROC curve was used to determine the best cut-off point. RESULTS: The sample
      was composed of 747 patients. Most were men (66%), white (85%) and married (61%).
      Mean age was 50 +/- 17 years, and mean level of education was 6 +/- 4 years.
      According to the MINI, 48 patients (6.6%) were diagnosed as having alcohol
      dependence. The CAGE questionnaire presented its highest sensitivity (93.8%) when
      the cut-off point of 0/1 (one or more "positive" responses indicating a positive
      test) was used. The specificity for this cut-off point was 85.5%. CONCLUSION:
      Using the 0/1 cut-off point, the CAGE questionnaire presented good sensitivity
      (93.8%) and specificity (85.5%) for use in general hospital ward patients. Since
      it is an easily applied, rapidly executed and inexpensive instrument, it could be
      useful in screening such patients for alcohol dependence.

PMID- 15867985
TI  - Accuracy of psychiatric diagnosis performed under indirect supervision.
AB  - This work aimed at comparing the accuracy of the psychiatric diagnoses made under
      indirect supervision to the diagnoses obtained through Structured Clinical
      Interview for DSM-III-R (SCID). The study was conducted in 3 university services
      (outpatient, inpatient and emergency). Data from the emergency service were
      collected 3 years later, after changes in the training process of the medical
      staff in psychiatric diagnosis. The sensitivity for Major Depression (outpatient
      10.0%; inpatients 60.0%, emergency 90.0%) and Schizophrenia (44.4%; 55.0%; 80.0%)
      improved over time. The reliability was poor in the outpatient service (Kw =
      0.18), and at admission to the inpatient service (Kw = 0.38). The diagnosis
      elaborated in the discharge of the inpatient service (Kw = 0.55) and in the
      emergency service (Kw = 0.63) was good. Systematic training of supervisors and
      residents in operational diagnostic criteria increased the accuracy of
      psychiatric diagnoses elaborated under indirect supervision, although excellent
      reliability was not achieved.

PMID- 15867986
TI  - The cross-cultural adaptation to Portuguese of the Trauma History Questionnaire
      to identify traumatic experiences.
AB  - BACKGROUND: Despite the high prevalence of exposure to traumatic events in
      Brazil, there are few studies on trauma and post-traumatic stress disorder. This
      paper presents the cross-cultural adaptation to Portuguese of the Trauma History
      Questionnaire. METHODS: Two translations and their respective back-translations
      were made, as well as the evaluation of the semantic equivalence, the preparation
      of the synthesis version, the pre-testing in the target population and the
      definition of the final version. DISCUSSION: Similar levels of referential
      meaning between the two back-translations and the original instrument were
      observed. Priority was given to the first translation in the decision process for
      the elaboration of the synthesis version. The pre-testing of this version in the
      target population confirmed the goal to achieve the semantic and the operational
      equivalence criteria. This work offers the first adaptation of a specific
      instrument to detect traumatic experiences in the Brazilian context.

PMID- 15867987
TI  - Quality of Life in siblings of autistic patients.
AB  - OBJECTIVE: To evaluate the Quality of Life (QoL) among siblings of autistic
      patients. METHODS: Casuistic: siblings of autistic patients (n = 31) and, as a
      control group, siblings of patients with speech disorder (n = 30). INCLUSION
      CRITERIA: age between 7 and 11 years old; absence of current mental disorder;
      regular attendance to school. EXCLUSION CRITERIA: antecedents of clinical or
      psychiatric diseases; disabilities (visual, auditive or motor); antecedents of
      cognitive and/or intelligence disabilities. Instruments included a questionnaire
      which evaluated the quality of life in a subjective way. RESULTS: it was observed
      worse QoL among siblings of autistic patients (p = 0.000). CONCLUSION: The
      hypothesis that the quality of life was compromised in children (aged 7 to 11) by
      the presence of an autistic sibling was confirmed, and was worse than that of
      siblings of children with speech disorders.

PMID- 15867988
TI  - [Brain effects of cannabis--neuroimaging findings].
AB  - Cannabis is the most widely used illicit drug. Despite this, only a small number
      of studies have investigated the long-term neurotoxic consequences of cannabis
      use. Structural and functional neuroimaging techniques are powerful research
      tools to investigate possible cannabis-induced pathophysiological changes. A
      computer literature review was conducted in the MEDLINE and PsycLIT databases
      between 1966 and November of 2004 with the search terms 'cannabis', 'marijuana',
      'neuroimaging', 'magnetic resonance', 'computed tomography', 'positron emission
      tomography', 'single photon emission computed tomography", 'SPET', 'MRI' and
      'CT'. Structural neuroimaging studies have yielded conflicting results. Most
      studies report no evidence of cerebral atrophy or regional changes in tissue
      volumes, and one study suggested that long-term users who started regular use on
      early adolescence have cerebral atrophy as well as reduction in gray matter.
      However, several methodological shortcomings limit the interpretation of these
      results. Functional neuroimaging studies have reported increases in neural
      activity in regions that may be related with cannabis intoxication or mood-change
      effects (orbital and mesial frontal lobes, insula, and anterior cingulate) and
      decreases in activity of regions related with cognitive functions impaired during
      acute intoxication. The important question whether residual neurotoxic effects
      occur after prolonged and regular use of cannabis remains unclear, with no study
      addressing this question directly. Better designed neuroimaging studies, combined
      with cognitive evaluation, may be elucidative on this issue.

PMID- 15867989
TI  - [Decline of cognitive capacity during aging].
AB  - Decline of cognitive capacity (DCC) is due to normal physiological aging
      processes or to pre-dementia stage. Epidemiological studies show that elderly
      with decline of cognitive capacity have higher risk to develop Alzheimer's
      disease (AD), especially those with episodic memory deficits. This review
      presents the most important diagnosis criteria, neuropathological and
      neuropsychological findings of decline of cognitive capacity during aging.

PMID- 15867990
TI  - [Early diagnosis of bipolar disorder].

PMID- 15867991
TI  - [Cardiovascular risk factors in Brazil: the next 50 years!].

PMID- 15867992
TI  - [Myocardial revascularization in patients with multivessel disease].

PMID- 15867993
TI  - [Risk factors associated with acute myocardial infarction in the Sao Paulo
      metropolitan region: a developed region in a developing country].
AB  - OBJECTIVE: To identify the risk factors associated with acute myocardial
      infarction (AMI) and their respective powers of association in the Sao Paulo
      metropolitan region. METHODS: The cases comprised patients diagnosed with first
      AMI with an ST segment elevation. The controls were individuals with no known
      cardiovascular disease. The study comprised 271 cases and 282 controls from 12
      hospitals. Risk factors were as follows: ethnic group; educational level; marital
      status; family income; family history of coronary artery disease; antecedents of
      arterial hypertension and of diabetes mellitus; hormonal replacement in women;
      smoking; physical activity; alcohol consumption; total cholesterol, LDL
      cholesterol, HDL-cholesterol, triglyceride, and glucose levels; body mass index;
      and waist-hip ratio (WHR). RESULTS: The following risk factors showed and
      independent association with AMI: smoking [odds ratio (OR) = 5.86; 95% confidence
      interval (CI) 3.25-10.57; P < 0.00001); waist-hip ratio (first vs. third tertile)
      (OR = 4.27; 95% CI 2.28-8.00; P < 0.00001); antecedents of arterial hypertension
      (OR = 3.26; 95% CI 1.95-5.46; P < 0.00001); waist-hip ratio (first vs second
      tertile) (OR = 3.07; 95% CI 1.66-5.66; P = 0.0003); LDL-cholesterol level (OR =
      2.75; 95% CI 1.45-5.19; P = 0.0018); antecedents of diabetes mellitus (OR = 2.51;
      95% CI 1.45-5.19; P = 0.023); family history of coronary artery disease (OR =
      2.33; 95% CI 1.44-3.75; P = 0.0005); and HDL-cholesterol level (OR = 0.53; 95% CI
      0.32-0.87; P = 0.011). CONCLUSION: Smoking, waist-hip ratio, antecedents of
      arterial hypertension and of diabetes mellitus, family history of coronary artery
      disease, and LDL-cholesterol and HDL-cholesterol levels showed to be
      independently associated with AMI within the Sao Paulo metropolitan region.

PMID- 15867994
TI  - [Comparative study of the results of coronary artery bypass grafting and
      angioplasty for myocardial revascularization in patients with equivalent
      multivessel disease].
AB  - OBJECTIVE: To investigate the relative efficacy of different therapeutic
      strategies in patients with symptomatic multivessel coronary artery disease with
      preserved ventricular function. The primary objectives were defined as a
      combination of death of cardiac origin, acute myocardial infarction (AMI), and
      refractory angina that required revascularization, and the secondary objectives
      were defined as anginal state and exercise-induced ischemia. METHODS: Of the
      20,769 patients assessed on cine coronary angiography at InCor, 210 were chosen
      for this study and were randomized either for coronary artery bypass grafting
      (CABG, n = 105) or transluminal coronary angioplasty (TCA, n = 105). RESULTS: A
      mean of 3.2 +/- 0.8 vessels received anastomoses and 2.1 +/- 0.8 were
      successfully dilated in the CABG and TCA groups, respectively. In a 5-year follow
      up, the rates of events in the CABG and TCA groups were, respectively: mortality,
      9.52% and 12.38%; acute myocardial infarction, 2.85% and 8.57% (P = 0.0668); and
      additional intervention, 2.85% and 24.76% (P < 0.001). The survival rate was
      88.39% for CABG and 84.93% for TCA; the respective AMI-free percentages were
      84.40% and 77.40%. In the CABG and TCA groups, 62% and 60% of the patients had no
      angina, respectively. The exercise tests were considered nonischemic in 62.5% and
      62.1% of the patients in the CABG and TCA groups, respectively. CONCLUSION: In
      multivessel patients, compared with angioplasty, coronary artery bypass grafting
      was associated with a lower incidence of long-term events and a reduced need for
      new interventions (P = 0.001).

PMID- 15867995
TI  - [Relation between left atrial dimension and exercise capacity in endomyocardial
      fibrosis].
AB  - OBJECTIVE: To assess whether exercise capacity is related to left atrial
      dimension (LAD) in patients with biventricular endomyocardial fibrosis. METHODS:
      This study comprised 38 patients in sinus rhythm, with a mean age of 37.5 +/-
      11.5 years (range, 11 to 59 years), 25 of whom were women. They were divided into
      2 groups according to the NYHA functional class on hospital admission as follows:
      group A (12 patients) and group B (26 patients). All patients underwent
      cardiopulmonary exercise testing to determine their maximum oxygen consumption
      (VO2 max), and their left atrial dimension was determined on echocardiography.
      RESULTS: The VO2max values for groups A and B were 21.8 +/- 4.8 mL.kg(-1).min(-1)
      and 13.7 +/- 3.5 mL.kg(-1).min(-1), respectively, and the left atrial dimensions
      were 3.7 +/- 0.7 cm and 4.4 +/- 0.7 cm for groups A and B, respectively. A
      significant and inverse correlation was found between VO2max and LAD in the
      groups studied. CONCLUSION: The increase in left atrial dimension is associated
      with impairment in exercise capacity in patients with endomyocardial fibrosis.
      Our findings support the use of left atrial dimension to estimate a more complex
      and difficult to assess index of functional capacity, such as VO2max.

PMID- 15867996
TI  - [Effects of the prolonged inhibition of the angiotensin-converting enzyme on the
      morphological and functional characteristics of left ventricular hypertrophy in
      rats with persistent pressure overload].
AB  - OBJECTIVE: To assess the effects of lisinopril (L) on mortality (M) rate and
      congestive heart failure (CHF), and the characteristics of geometrical myocardial
      remodeling and left ventricular function in rats with supravalvular aortic
      stenosis (SAS). METHODS: Some Wistar rats underwent SAS or the simulated surgery
      (CG, n=10). After 6 weeks, the animals were randomized to receive lisinopril (LG,
      n=30) or no treatment (SG, n=73) for 15 weeks. Cardiac remodeling was assessed in
      the sixth and 21st weeks after the surgical procedures through concomitant
      echocardiographic, hemodynamic, and morphological studies. RESULTS: The M were
      53.9% and 16.7% in SG and LG, respectively; the incidence of CHF was 44.8% and
      20%, in SG and LG, respectively, (P<0.05). At the end of the experiment, the
      values of LV systolic pressure in SG and LG were equivalent and significantly
      greater than those in CG; (P<0.05) and did not differ from those observed 6 weeks
      after the surgical procedures. The values of LV diastolic pressure in SG were
      greater than those in LG; (P<0.05), and both were greater than those in CG;
      (P<0.05). The same behavior was observed with the following variables: E/A ratio;
      mass index; sectional area of the myocytes; and LV hydroxyproline content. Left
      ventricular shortening percentage was similar in CG and LG; (P>0.05), and both
      were greater than those in SG; (P<0.05). Similar results were obtained with the
      values of the positive and negative first derivate of LV pressure. CONCLUSION: In
      rats with SAS, the treatment with L reduced M rate and ICC and had beneficial
      effects on geometrical myocardial remodeling and left ventricular function.

PMID- 15867997
TI  - [Initial analysis of the use of the L-D-Hydro (Eato L-D-Hydro) organic tubular
      graft for performing the modified Blalock-Taussig procedure in congenital heart
      diseases with decreased pulmonary blood flow].
AB  - OBJECTIVE: To analyze the initial results of the use of an organic tubular graft
      for systemic-pulmonary anastomoses. METHODS: From March 2002 to April 2003, 10
      patients underwent systemic-pulmonary shunt of the modified Blalock-Taussig type,
      using a new type of biological graft originating from the bovine mesenteric
      artery treated with polyglycol, the so-called L-D-Hydro. The patients' ages
      ranged from 3 days to 7 years, and 60% of them were of the male sex. The
      diagnoses of heart disease were determined on echocardiography. All patients had
      clinical signs of severe hypoxia (cyanosis). The heart diseases were as follows:
      tetralogy of Fallot (40%), tricuspid atresia (50%), and atrioventricular septal
      defect (10%). RESULTS: One patient died due to sepsis and 9 had an immediate
      improvement in O2 saturation on pulse oximetry and in the partial oxygen pressure
      on arterial blood gas analysis. The intensive care unit length of stay ranged
      from 2 to 6 days. No patient had obstruction of the shunt on the immediate
      postoperative period or any other complication. All patients had a patent shunt
      on the echocardiographic studies performed in the immediate postoperative period
      and later, in the third postoperative month. No bleeding occurred during surgery
      or in the postoperative period. CONCLUSION: The tubular L-D-Hydro graft proved to
      be promising for performing systemic-pulmonary shunt as an alternative for the
      inorganic products available in the market, however, we need a greater number of
      implantations and late follow-up for definitive assessment.

PMID- 15867998
TI  - [Anemia as a prognostic factor in a population hospitalized due to decompensated
      heart failure].
AB  - OBJECTIVE: To study the prevalence and prognostic value of anemia in a population
      hospitalized due to decompensated heart failure. METHOD: From July to September,
      2001, 204 patients were included in a multicenter hospital registry of heart
      failure (EPICA Study--Niteroi). This retrospective analysis comprised 142
      patients with data about hematocrit and hemoglobin levels collected on hospital
      admission. The mean age was 69.5+/-13.3 years, and 72 (50.7%) patients were men.
      Hemoglobin levels < 13.5 g/dL for men and < 12 g/dL for women were considered
      anemia. The relation between anemia and in-hospital mortality was assessed
      through univariate and multivariate analysis with logistic regression. RESULTS:
      Anemia was observed in 89 (62.6%) patients, 52 (58%) men and 37 (42%) women.
      Mortality in anemic patients was 16.8% and, in nonanemic, it was 8% (P=0.11). In
      both sexes, the mortality rates in anemic and nonanemic patients were,
      respectively, 19.2% vs 0% (P=0.034) and 13.5% vs 12.2% (P=0.86). Through
      multivariate analysis, the following variables were found to be independently
      related to in-hospital mortality: hyponatremia [RR=7.0; 95% confidence interval
      (95% CI)=6.1 to 8.7; P=0.0001], anemia (RR=3.1, 95% CI=2.4 to 4.3; P=0.024), and
      presence of NYHA functional class IV (RR=1.9; 95% CI=1.3 to 2.6; P=0.04).
      CONCLUSION: In the population studied with decompensated heart failure, the
      presence of anemia was an independent marker of in-hospital mortality. Mortality
      in the group with anemia was significantly high among men.

PMID- 15867999
TI  - [Quantitative assessment of left ventricular regional wall motion in
      endomyocardial fibrosis].
AB  - OBJECTIVE: To analyze left ventricular (LV) regional wall motion in patients with
      endomyocardial fibrosis (EMF). METHODS: The study comprised 88 patients, 59 of
      the female sex, with a mean age of 39+/-13 years (range, 9 to 65) and with
      echocardiographic and angiographic evidence of left ventricular EMF. The
      intensity of fibrous tissue buildup on contrast cineventriculography was
      classified as mild, moderate, or severe. The overall left ventricular ejection
      fraction (LVEF) was determined by using the area-length method on
      ventriculography. The motion was measured in 100 equidistant chords perpendicular
      to the centerline drawn in the middle of the final diastolic and systolic
      contours and normalized to cardiac size. Five left ventricular segments were
      analyzed: A--apical; AL--anterolateral; AB--anterobasal; IA--inferoapical; IB-
      inferobasal. Abnormality was expressed in units of standard deviation of the mean
      motion in a normal population of reference, comprised of 103 patients with normal
      LV according to clinical and electrocardiographic data, and angiographic
      standards. RESULTS: Mean LVEF was 0.47+/-0.12. Fibrous tissue buildup in the left
      ventricle was mild in 12 patients, moderate in 40, and severe in 36. The regions
      with the poorest ventricular wall motion were A (-1.4+/-1.6 standard
      deviation/chords) and IA (-1.6+/-1.8 standard deviation/chords) compared with
      that in AB (-0.3+/-1.9 standard deviation/chords), AL (-0.5+/-1.8 standard
      deviation/chords) and IB (-0.9+/-1.3 standard deviation/chords). No relation was
      observed between the intensity of fibrous tissue buildup and regional ventricular
      wall motion. CONCLUSION: A change in LV regional wall motion exists in EMF, and
      it is independent of the intensity of fibrous tissue buildup qualitatively
      assessed. Nonuniform involvement of the LV should be considered when planning
      surgery for this disease.

PMID- 15868000
TI  - [Echocardiographic monitoring of balloon atrial septostomy].
AB  - OBJECTIVE: To assess balloon atrial septostomy monitored with echocardiography.
      METHODS: From August 1997 to January 2004, 31 infants with congenital heart
      diseases indicated for balloon atrial septostomy underwent the procedure with
      exclusive echocardiographic monitoring. Success was defined as the obtainment of
      an atrial septal defect diameter > 4 mm and ample mobility of its margins.
      RESULTS: The male sex predominated (83.9%). The median age was 5 days (1-150),
      and the median weight was 3,300 g (1,800-7,500). Transposition of the great
      arteries occurred in 80.6% of the patients, tricuspid valve atresia in 12.9%,
      total anomalous pulmonary venous drainage in 3.2%, and pulmonary atresia with
      intact septum in 3.2%. The procedure was successful in all patients. The size of
      the atrial septal defect increased from 1.8 +/- 0.8 mm to 5.8 +/- 1.3 mm (P <
      0.0001) and oxygen arterial saturation from 64.5 +/- 18.9% to 85.1 +/- 9.2% (P <
      0.0001). The following complications occurred: 3 balloon ruptures, one lesion of
      the right femoral vein, one supraventricular tachycardia, and one atrial flutter.
      CONCLUSION: Balloon atrial septostomy monitored with echocardiography is a safe
      and effective procedure. It may be performed at bedside, avoiding transporting of
      the patient, identifies the catheter location, reduces the occurrence of severe
      complications, and assesses the immediate result of the procedure.

PMID- 15868001
TI  - [Amiodarone causes endothelium-dependent vasodilation in canine coronary
      arteries].
AB  - OBJECTIVE: To assess the vasodilating effects of amiodarone on canine coronary
      arteries by using solutions of amiodarone dissolved in polysorbate 80 or water.
      METHODS: Rings of coronary arteries, with or without intact endothelium, were
      immersed in Krebs solution and connected to a transducer for measuring the
      isometric force promoted by a vascular contraction. The arteries were exposed to
      increasing concentrations of polysorbate 80, amiodarone dissolved in water,
      amiodarone dissolved in polysorbate 80, and a commercial presentation of
      amiodarone (Cordarone). The experiments were conducted in the presence of the
      following enzymatic blockers: only indomethacin, Nomega-nitro-L-arginine
      associated with indomethacin, and only Nomega-nitro-L-arginine. RESULTS:
      Polysorbate 80 caused a small degree of nonendothelium-dependent relaxation.
      Cordarone, amiodarone dissolved in water, and amiodarone dissolved in polysorbate
      80 caused endothelium-dependent relaxation, which was greater for amiodarone
      dissolved in polysorbate and for Cordarone. Only the association of indomethacin
      and Nomega-nitro-L-arginine could eliminate the endothelium-dependent relaxation
      caused by amiodarone dissolved in polysorbate 80. CONCLUSION: The results
      obtained indicate that vasodilation promoted by amiodarone in canine coronary
      arteries is mainly caused by stimulation of the release of nitric oxide and
      cyclooxygenase-dependent relaxing endothelial factors.

PMID- 15868002
TI  - [Batimastat-eluting stent implantation for the treatment of coronary artery
      disease: results of the Brazilian pilot study].
AB  - OBJECTIVE: The excellent results obtained with sirolimus (rapamicin)-eluting
      stents for preventing restenosis have motivated the evaluation of other
      substances with that property. Batimastat is a highly effective metalloproteinase
      enzyme blocker, with the potential to reduce the degradation of extracellular
      matrix and to inhibit the migration of smooth muscle cells, with the consequent
      capacity to control coronary restenosis. METHODS: From October 2001 to April
      2002, 34 patients were prospectively selected with de novo lesions in a native
      coronary artery > 50% and < 100%, which could be treated with stents of 3 to 4 mm
      in diameter and 18 mm in length. The primary outcome of the study was to assess
      the occurrence of major cardiovascular events (death of cardiac origin, acute
      myocardial infarction, and the need for revascularizing the target vessel) by the
      30th day and fourth month; the secondary outcome of the study was to assess the
      rate of coronary restenosis 4 months after implantation and subacute thrombosis
      by the 30th day. RESULTS: The success rate of the procedure was 97.1%. The
      primary outcome occurred in 2.9% and 27.2% of the patients by the 30th day and
      fourth month, respectively. The binary restenosis rate on angiography was 39.3%.
      No episode of subacute thrombosis occurred. The comparative analysis between
      groups with and without restenosis showed no significant difference between both,
      except for late luminal loss, which was greater in G-I. CONCLUSION: Batimastat
      eluting stents had a good safety profile; however, they were not effective in
      controlling coronary restenosis.

PMID- 15868003
TI  - [Comparative analysis of the flows of left internal thoracic artery grafts
      dissected in the pedicled versus skeletonized manner for myocardial
      revascularization surgery].
AB  - OBJECTIVE: To compare the free blood flow, caliber, and length of the left
      internal thoracic artery (LITA), dissected in the pedicled (P) and skeletonized
      (S) manners, during surgery before and after topical vasodilator (TV)
      application. METHODS: A randomized, blind, clinical trial was carried out with 50
      patients undergoing elective myocardial revascularization to assess the use of
      the LITA in situ in its pedicled or skeletonized form. The 25 patients in the
      pedicled group (GP) had NYHA class II or III angina, ejection fraction (EF) of
      50.8+/-9.2%, and 16 were of the male sex. The patients in the skeletonized group
      (SG) had NYHA class II angina, EF of 46.8+/-9.3%, and 19 were of the male sex.
      The measurements were performed before extracorporeal circulation and divided
      into 2 phases: phase 1 (before topical papaverine application) and phase 2 (15
      min after topical application of papaverine, 2.5 mg/mL, at 37 degrees C). During
      the measurements, mean blood pressure, central venous pressure, and heart rate
      were monitored. RESULTS: The phase 1 and 2 results are as follows: 1) PG: blood
      flow, 46+/-16 and 77+/-28 mL/min; caliber, 1.4+/-0.1 and 1.7+/-0.1 mm,
      respectively; 2) SG: blood flow, 57+/-27 and 97+/-35 mL/min; and caliber, 1.4+/
      0.1 and 1.8+/-0.2 mm, respectively. No significant differences were observed in
      length. CONCLUSION: The LITA in SG had a significant increase in blood flow and
      caliber after the use of TV compared with blood flow and caliber in PG (P=0.03
      and P=0.01, respectively).

PMID- 15868004
TI  - [Pheochromocytoma in childhood].
AB  - Pheochromocytoma is a neoplasia of chromaffin cells that is very rare in
      children. Its signs and symptoms result from the release of catecholamines. We
      report the case of a child with pheochromocytoma of difficult clinical
      management, confirmed on the anatomicopathological study, and cured after
      surgical resection.

PMID- 15868005
TI  - [Large coronary-pulmonary artery fistulae: percutaneous embolization with
      microcoils and disposable balloons].
AB  - A 43-year-old symptomatic woman (dyspnea and palpitation) had multiple coronary
      pulmonary artery fistulae with high output; percutaneous embolization was
      successfully performed using controlled-release microcoils and disposable
      balloons.

PMID- 15868006
TI  - [Guidelines for certification of training centers and for obtaining the
      Certification in Hemodynamics and Interventional Cardiology].

PMID- 15868007
TI  - [Anomalous T waves in complete left bundle branch block in non-compaction
      cardiomyopathy of the left ventricle].

PMID- 15868008
TI  - [Multiple simultaneous embolisms of right and left coronary arteries].

PMID- 15868011
TI  - Uganda leads way in innovative HIV/AIDS treatment.

PMID- 15868012
TI  - Disabled often among the 'poorest of poor'.

PMID- 15868013
TI  - Fighting the 'silent epidemic'.

PMID- 15868015
TI  - Staff training and ambulatory tuberculosis treatment outcomes: a cluster
      randomized controlled trial in South Africa.
AB  - OBJECTIVE: To assess whether adding a training intervention for clinic staff to
      the usual DOTS strategy (the internationally recommended control strategy for
      tuberculosis (TB)) would affect the outcomes of TB treatment in primary care
      clinics with treatment success rates below 70%. METHODS: A cluster randomized
      controlled trial was conducted from July 1996 to July 2000 in nurse-managed
      ambulatory primary care clinics in Cape Town, South Africa. Clinics with
      successful TB treatment completion rates of less than 70% and annual adult
      pulmonary TB loads of more than 40 patients per year were randomly assigned to
      either the intervention (n = 12) or control (n = 12) groups. All clinics
      completed follow-up. Treatment outcomes were measured in cohorts of adult,
      pulmonary TB patients before the intervention (n = 1200) and 9 months following
      the training (n = 1177). The intervention comprised an 18-hour experiential,
      participatory in-service training programme for clinic staff delivered by nurse
      facilitators and focusing on patient centredness, critical reflection on
      practice, and quality improvement. The main outcome measure was successful
      treatment, defined as patients who were cured and those who had completed
      tuberculosis treatment. FINDINGS: The estimated effect of the intervention was an
      increase in successful treatment rates of 4.8% (95% confidence interval (CI): 
      5.5% to 15.2%) and in bacteriological cure rates of 10.4% (CI: -1.2% to 22%). A
      treatment effect of 10% was envisaged, based on the views of policy-makers on the
      minimum effect size for large-scale implementation. CONCLUSION: This is the first
      evidence from a randomized controlled trial on the effects of experiential,
      participatory training on TB outcomes in primary care facilities in a developing
      country. Such training did not appear to improve TB outcomes. However, the
      results were inconclusive and further studies are required.

PMID- 15868016
TI  - Quality of care for under-fives in first-level health facilities in one district
      of Bangladesh.
AB  - OBJECTIVE: The multi-country evaluation of Integrated Management of Childhood
      Illness (IMCI) effectiveness, cost and impact (MCE) is a global evaluation to
      determine the impact of IMCI on health outcomes and its cost-effectiveness. MCE
      studies are under way in Bangladesh, Brazil, Peru, Uganda and the United Republic
      of Tanzania. The objective of this analysis from the Bangladesh MCE study was to
      describe the quality of care delivered to sick children under 5 years old in
      first-level government health facilities, to inform government planning of child
      health programmes. METHODS: Generic MCE Health Facility Survey tools were
      adapted, translated and pre-tested. Medical doctors trained in IMCI and these
      tools conducted the survey in all 19 health facilities in the study areas. The
      data were collected using observations, exit interviews, inventories and
      interviews with facility providers. FINDINGS: Few of the sick children seeking
      care at these facilities were fully assessed or correctly treated, and almost
      none of their caregivers were advised on how to continue the care of the child at
      home. Over one-third of the sick children whose care was observed were managed by
      lower-level workers who were significantly more likely than higher-level workers
      to classify the sick child correctly and to provide correct information on home
      care to the caregiver. CONCLUSION: These results demonstrate an urgent need for
      interventions to improve the quality of care provided for sick children in first
      level facilities in Bangladesh, and suggest that including lower-level workers as
      targets for IMCI case-management training may be beneficial. The findings suggest
      that the IMCI strategy offers a promising set of interventions to address the
      child health service problems in Bangladesh.

PMID- 15868017
TI  - Polio eradication: mobilizing and managing the human resources.
AB  - Between 1988 and 2004, the Global Polio Eradication Initiative grew to become the
      largest international health effort in history, operating in every country of the
      world. An estimated 10 million health workers and volunteers have been engaged in
      implementing the necessary polio supplementary immunization activities (SIAs) on
      a recurring basis, and at least 35,000 well-trained workers have been conducting
      polio surveillance. A combination of task simplification, technological
      innovations and adaptation of strategies to fit local circumstances has allowed
      the Initiative to use a wide range of workers and volunteers, from both inside
      and outside the health sector, to deliver the polio vaccine during SIAs and to
      monitor progress in virtually every area of every country, regardless of the
      health infrastructure, conflict, geography and/or culture. This approach has
      required sustained political advocacy and mass community mobilization, together
      with strong management and supervisory processes. Non-monetary incentives,
      reimbursement of costs and substantial technical assistance have been essential.
      Given the unique features of eradication programmes in general, and polio
      eradication in particular, the implications of this approach for the broader
      health system must continue to be studied if it is to be replicated for the
      delivery and monitoring of other interventions.

PMID- 15868018
TI  - Private sector, human resources and health franchising in Africa.
AB  - In much of the developing world, private health care providers and pharmacies are
      the most important sources of medicine and medical care and yet these providers
      are frequently not considered in planning for public health. This paper presents
      the available evidence, by socioeconomic status, on which strata of society
      benefit from publicly provided care and which strata use private health care.
      Using data from The World Bank's Health Nutrition and Population Poverty Thematic
      Reports on 22 countries in Africa, an assessment was made of the use of public
      and private health services, by asset quintile groups, for treatment of diarrhoea
      and acute respiratory infections, proxies for publicly subsidized services. The
      evidence and theory on using franchise networks to supplement government
      programmes in the delivery of public health services was assessed. Examples from
      health franchises in Africa and Asia are provided to illustrate the potential for
      franchise systems to leverage private providers and so increase delivery-point
      availability for public-benefit services. We argue that based on the established
      demand for private medical services in Africa, these providers should be included
      in future planning on human resources for public health. Having explored the
      range of systems that have been tested for working with private providers, from
      contracting to vouchers to behavioural change and provider education, we conclude
      that franchising has the greatest potential for integration into large-scale
      programmes in Africa to address critical illnesses of public health importance.

PMID- 15868019
TI  - Ethical issues in health workforce development.
AB  - Increasing the numbers of health workers and improving their skills requires that
      countries confront a number of ethical dilemmas. The ethical considerations in
      answering five important questions on enabling health workers to deal
      appropriately with the circumstances in which they must work are described. These
      include the problems of the standards of training and practice required in
      countries with differing levels of socioeconomic development and different
      priority diseases; how a society can be assured that health practitioners are
      properly trained; how a health system can support its workers; diversion of
      health workers and training institutions; and the teaching of ethical principles
      to student health workers. The ethics of setting standards for the skills and
      care provided by traditional health-care practitioners are also discussed.

PMID- 15868020
TI  - Intervention complexity--a conceptual framework to inform priority-setting in
      health.
AB  - Health interventions vary substantially in the degree of effort required to
      implement them. To some extent this is apparent in their financial cost, but the
      nature and availability of non-financial resources is often of similar
      importance. In particular, human resource requirements are frequently a major
      constraint. We propose a conceptual framework for the analysis of interventions
      according to their degree of technical complexity; this complements the notion of
      institutional capacity in considering the feasibility of implementing an
      intervention. Interventions are categorized into four dimensions: characteristics
      of the basic intervention; characteristics of delivery; requirements on
      government capacity; and usage characteristics. The analysis of intervention
      complexity should lead to a better understanding of supply- and demand-side
      constraints to scaling up, indicate priorities for further research and
      development, and can point to potential areas for improvement of specific aspects
      of each intervention to close the gap between the complexity of an intervention
      and the capacity to implement it. The framework is illustrated using the examples
      of scaling up condom social marketing programmes, and the DOTS strategy for
      tuberculosis control in highly resource-constrained countries. The framework
      could be used as a tool for policy-makers, planners and programme managers when
      considering the expansion of existing projects or the introduction of new
      interventions. Intervention complexity thus complements the considerations of
      burden of disease, cost-effectiveness, affordability and political feasibility in
      health policy decision-making. Reducing the technical complexity of interventions
      will be crucial to meeting the health-related Millennium Development Goals.

PMID- 15868021
TI  - Human resources for the control of road traffic injury.
AB  - The definition of the ideal numbers and distribution of human resources required
      for control of road traffic injury (RTI) is not as advanced as for other health
      problems. We can nonetheless identify functions that need to be addressed across
      the spectrum of injury control: surveillance; road safety (including
      infrastructure, vehicle design, and behaviour); and trauma care. Many low-cost
      strategies to improve these functions in low- or middle-income countries can be
      identified. For all these strategies, there is need for adequate institutional
      capacity, including funding, legal authority, and human resources. Several
      categories of human resources need to be developed: epidemiologists who can
      handle injury data, design surveillance systems, and undertake research;
      engineers and planners versed in safety aspects of road design, traffic flow,
      urban planning, and vehicle design; police and lawyers who understand the health
      impact of traffic law; clinicians who can develop cost-effective improvements in
      the entire system of trauma treatment; media experts to undertake effective
      behaviour change and social marketing; and economists to assist with cost
      effectiveness evaluations. RTI control can be strengthened by enhancing such
      training in these disciplines, as well as encouraging retention of those who have
      the needed skills. Mechanisms to enhance collaboration between these different
      fields need to be promoted. Finally, the burden of RTI is borne
      disproportionately by the poor; in addition to technical issues, more profound
      equity issues must be addressed. This mandates that people from all professional
      backgrounds who work for RTI control should develop skills in advocacy and
      politics.

PMID- 15868022
TI  - Advance price or purchase commitments to create markets for treatments for
      diseases of poverty: lessons from three policies.
AB  - New drugs and vaccines are needed for tackling diseases of poverty in low- and
      middle-income countries. The lack of effective demand or market for these
      products translates into insufficient investment being made in research and
      development to meet the need for them. Many have advocated cost-reducing (push)
      and market-enhancing (pull) incentives to tackle this problem. Advance price or
      purchase commitments (APPCs) funded by international agencies and governments
      offer one way forward. This paper looks at design issues for APPCs for drugs and
      vaccines for diseases of poverty drawing on experience and lessons from three
      case studies: the introduction of the meningitis C vaccine in the United Kingdom;
      the Orphan Drug Act (ODA) in the United States of America (US); and the newly
      legislated US Project BioShield for bioterrorist interventions. Our key
      conclusion is that that APPCs have the potential to be a powerful tool and should
      be tried. The correct structure and design may only be determined through the
      process of taking action to set one up.

PMID- 15868024
TI  - Mass campaigns versus general health services: what have we learnt in 40 years
      about vertical versus horizontal approaches?

PMID- 15868023
TI  - Understanding dengue pathogenesis: implications for vaccine design.
AB  - In the second half of the twentieth century dengue spread throughout the tropics,
      threatening the health of a third of the world's population. Dengue viruses cause
      50-100 million cases of acute febrile disease every year, including more than
      500,000 reported cases of the severe forms of the disease--dengue haemorrhagic
      fever and dengue shock syndrome. Attempts to create conventional vaccines have
      been hampered by the lack of suitable experimental models, the need to provide
      protection against all four serotypes simultaneously and the possible involvement
      of virus-specific immune responses in severe disease. The current understanding
      of dengue pathogenesis is outlined in this review, with special emphasis on the
      role of the immune response. The suspected involvement of the immune system in
      increased disease severity and vascular damage has raised concerns about every
      vaccine design strategy proposed so far. Clearly more research is needed on
      understanding the correlates of protection and mechanisms of pathogenesis. There
      is, however, an urgent need to provide a solution to the escalating global public
      health problems caused by dengue infections. Better disease management, vector
      control and improved public health measures will help reduce the current disease
      burden, but a safe and effective vaccine is probably the only long-term solution.
      Although concerns have been raised about the possible safety and efficacy of both
      conventional and novel vaccine technologies, the situation is now so acute that
      it is not possible to wait for the perfect vaccine. Consequently the careful and
      thorough evaluation of several of the current candidate vaccines may be the best
      approach to halting the spread of disease.

PMID- 15868025
TI  - Public Health and tobacco control in Brazil.

PMID- 15868026
TI  - [Social stratification in epidemiological studies of dental caries and
      periodontal diseases: a profile of the scientific literature in the 1990s].
AB  - Several epidemiological studies have analyzed the association between oral health
      and social development. However, the use of different variables assessing
      socioeconomic status impairs the comparative analysis of their findings. The
      present study describes how recent dental studies have classified population
      segments according to categories of social stratification. We selected 86 papers
      on social determinants of dental caries or periodontal conditions, and published
      in MEDLINE-indexed journals from 1990 to 2001. The studies used different
      strategies to stratify populations, but occupation, schooling, and income were
      the most frequently assessed variables. Ethnic differentials, characteristics of
      households and schools, and access to material resources were also frequently
      appraised. We also observed a large portion of Brazilian studies focusing on
      socioeconomic differentials in the distribution of caries and periodontal
      disease. Knowledge of strategies for social stratification can improve the
      understanding of factors associated with dental diseases, fostering further
      studies and allowing the comparison of their results.

PMID- 15868027
TI  - [Brazilian public health research output related to the environment].
AB  - Although there are few scientific studies on the environment in the Brazilian
      public health literature, there are indications of recent growth in this theme in
      research and graduate programs in Brazil, thus tending to consolidate the
      scientific output in this area. The objective of this study was to contribute to
      the understanding and characterization of this theme in public health, offering
      backing for establishing research focused on sustainability of the environment
      and health. We identified and analyzed the research output on the environment in
      the most important Brazilian scientific journals in public health (1992-2002),
      using as the reference Chapter 35 of Agenda 21 (science for sustainability). The
      results showed: research output highly concentrated in the more affluent
      Southeast region of the country; predominance of the biological concept of health
      and the biophysical concept of environment; prevalence of diagnoses versus the
      search for solutions; and few studies involving stakeholders' participation.

PMID- 15868028
TI  - [Construct validity of the Medical Outcomes Study's social support scale adapted
      to Portuguese in the Pro-Saude Study].
AB  - This paper evaluates the construct validity of the Medical Outcomes Study's
      social support scale adapted to Portuguese, when utilized in a cohort study among
      non-faculty civil servants at a university in Rio de Janeiro, Brazil (Pro-Saude
      Study). Baseline data were obtained in 1999, when 4,030 participants (92.0% of
      those eligible) completed a multidimensional self-administered questionnaire at
      the workplace. From the original scale's five social support dimensions, factor
      analysis of the data extracted only three dimensions: positive social
      interaction/affective support; emotional/information support; and material
      support. We estimated associations between social support dimensions and socio
      demographic, health, and well being-related characteristics. We confirmed the
      hypotheses that less isolated individuals, those with better self-rated health,
      those who reported more participation in group activities, and those with no
      evidence of common mental disorders reported better perception of social support.
      In conclusion, we found good evidence for a high construct validity of this
      scale, supporting its use in future analyses in the Pro-Saude Study and in
      similar population groups.

PMID- 15868029
TI  - [Mothers' perspectives on infant death: an investigation beyond the statistics].
AB  - This qualitative study was conducted in Belo Horizonte, Minas Gerais, Brazil,
      focusing on infant death from the mothers' perspective. Sixteen mothers whose
      infants had died were interviewed. Mothers' narratives were analyzed by
      classifying such categories as perceptions of health-illness-death, the physician
      patient relationship, and quality of care. Discontinuity between prenatal and
      childbirth care, wandering from one hospital to another to receive care, and lack
      of communication with health care professionals were situations reported by the
      women. Feelings such as fear, solitude, abandonment, insecurity, and
      disempowerment were also evidenced. The inequity of rights was a dominant theme
      which permeated many narratives, revealing a process of exclusion for mothers and
      their children as users of the public health system.

PMID- 15868030
TI  - [Validation of food security and social support scales in an Afro-Colombian
      community: application on a prevalence study of nutritional status in children
      aged 6 to 18 months].
AB  - We conducted a cross-sectional study on 193 mothers of children 6 to 18 months of
      age in an African-Colombian community, with the objectives: (1) to adapt and
      validate the Community Childhood Hunger Identification Project scale, the DUKE
      UNC-11 social support scale, and the Quebec Longitudinal Study of Child
      Development (QLSCD) partner support scale, and (2) to identify any existent
      relationship between nutritional status in infancy and both food insecurity and
      social support. We determined construct validity using factor analysis and
      theoretical models-based non-parametric correlations. Length-for-age and weight
      for-length Z-results were calculated. Factor analyses reduced the hunger scale to
      one factor, the DUKE-UNC-11 scale to two factors, and the QLSCD scale to one
      factor. The Cronbach's alpha test ranged between 0.70 and 0.90. Both food
      insecurity and social support scales were correlated with mother's social
      conditions, and social support was positively associated with social networks and
      mother's self-perceived health status. Food insecurity, emotional-social support,
      and partner's negative support were associated with lower height-to-age and
      therefore a higher ratio of chronic malnutrition. The study supports the
      appropriateness of the instruments to measure the expressed concepts.

PMID- 15868031
TI  - [Work-related accidents, with biological materials, in health care workers in
      public hospitals in Brasilia, Brazil, 2002/2003].
AB  - This study evaluates the knowledge and acceptance of biosafety measures by health
      care professionals in light of the potential risk of occupational transmission of
      HIV. The survey assessed 570 health care workers from 6 hospitals, randomly
      selected from all hospitals in the Federal District (Brasilia), Brazil. The
      sample corresponds to 15.0% of the all health professionals in the selected
      hospitals. These professionals answered a semi-structured questionnaire on
      knowledge of biosafety and universal precautions, risk of occupational HIV
      transmission, work-related accidents, use of personal protective equipment (PPE),
      and acceptance of chemoprophylaxis and HIV testing. The overall accident
      coefficient was 39.1. Dentists, physicians, and laboratory technicians were those
      who most frequently suffered such accidents. The accident coefficient was
      inversely proportional to the hospital capacity. The professionals' knowledge of
      biosafety concepts and the fact that written norms were displayed in their
      workstations did not positively affect the work accident coefficient.

PMID- 15868032
TI  - [Confidentiality, genetic counseling, and public health: a case study on sickle
      cell trait].
AB  - Sickle cell anemia is the most prevalent genetic disease in Brazil. Screening for
      sickle cell trait in blood donation centers has been recommended by the Brazilian
      government since 1976. This screening mechanism is one of most common forms of
      genetic screening for sickle cell disease in the country. This article is based
      on an ethnographic survey of individuals undergoing genetic counseling in a large
      blood donation center. The article contends that confidentiality should be a
      prerequisite for the broad dissemination of genetic information in public health.
      The ethical principle of confidentiality needs to be seen as a human right and
      public health issue.

PMID- 15868033
TI  - [Breastfeeding practices and infant growth: a longitudinal study in Rio de
      Janeiro, Brazil, 1999/2001].
AB  - Various studies have shown significant differences in growth patterns between
      breastfed and formula-fed infants. This paper aims to evaluate the effect of
      predominant breastfeeding duration on anthropometric profile and to detect
      determinants associated with growth in Brazilian infants. Four hundred and
      seventy nine infants were studied in a health center in Rio de Janeiro through a
      longitudinal study with four follow-up waves at 0.5, 2, 6, and 9 months. The
      response variables were body weight and length, collected according to a
      standardized procedure. Data analysis was performed having longitudinal mixed
      effects model as the main statistical procedure. Gestational age, birth weight,
      and birth length were positively associated with weight and length gains. The
      positive effect showed that the longer breastfeeding lasts, the greater the
      weight gains. Infants born through vaginal delivery presented lower weight gains
      than those born by cesarean delivery. The results emphasize the need for health
      programs encouraging breastfeeding practices up to the sixth month of life.

PMID- 15868034
TI  - [Relationship between body mass index, waist circumference, and waist-to-hip
      ratio and mortality in elderly women: a 5-year follow-up study].
AB  - This study examines the association between body mass index (BMI), waist-to-hip
      ratio (WHR), and waist circumference (WC) and all-cause and cardiovascular
      mortality in elderly women in a 5-year longitudinal study of 575 female
      outpatients 60 years and over. The highest BMI, WHR, and WC quartiles and
      predefined BMI categories were analyzed as predictive variables. Death occurred
      in 88 (15.4%). Underweight (BMI < 18.5 kg/m2) was associated with all-cause
      mortality in uni- and multivariate analyses, regardless of age bracket. The
      survival curves and univariate analysis showed that the highest WHR quartile (>
      or = 0.97) was associated with all-cause mortality. However, after adjustment for
      age, smoking, and previous cardiovascular diseases, the increase in WHR was
      positively associated only in women from 60 to 80 years of age. None of the
      anthropometric measurements was associated with cardiovascular mortality. The
      results indicate that underweight and increased waist-to-hip ratio were
      predictors of all-cause mortality in elderly women, mainly among those under 80
      years.

PMID- 15868035
TI  - Evaluation of the impact of a nutritional program for undernourished children in
      Brazil.
AB  - To assess the effectiveness on child growth and body composition of a
      supplementary feeding program (Milk Supplement Program), a prospective,
      controlled study was conducted in Northeast Brazil. When entering the Program,
      children from 10 municipalities with the highest coverage rates in the Program
      (intervention group) were compared to non-beneficiary children from 10
      municipalities with the lowest coverage rates (control group). A total of 219
      children aged 6-18 months were enrolled. At entry, both groups were comparable in
      terms of age, sex, and nutritional status. There were frequent gaps in delivery
      of the supplement, no extra milk was provided to siblings less than 5 years of
      age, intra-household redistribution of milk was high, and maternal compliance
      with recommendations was low. Adjusted analyses by multilevel modelling showed
      average changes in weight, length, weight-age and length-age Z-scores, and % body
      water (deuterium method), at 6 months, of 1.53 kg, 6.34 cm, 0.33, 0.05, and 1.11%
      respectively among supplemented children as compared to 1.54 kg, 6.5 cm, 0.26,
      0.07, and 4.10% among controls, with no statistically significant difference
      between groups. Thus, the Program failed to compensate for nutritional
      deficiencies in undernourished children in Northeast Brazil.

PMID- 15868036
TI  - Similarity between neonatal profile and socioeconomic index: a spatial approach.
AB  - This study aims to compare neonatal characteristics and socioeconomic conditions
      in Rio de Janeiro city neighborhoods in order to identify priority areas for
      intervention. The study design was ecological. Two databases were used: the
      Brazilian Population Census and the Live Birth Information System, aggregated by
      neighborhoods. Spatial analysis, multivariate cluster classification, and Moran's
      I statistics for detection of spatial clustering were used. A similarity index
      was created to compare socioeconomic clusters with the neonatal profile in each
      neighborhood. The proportions of Apgar score above 8 and cesarean sections showed
      positive spatial correlation and high similarity with the socioeconomic index.
      The proportion of low birth weight infants showed a random spatial distribution,
      indicating that at this scale of analysis, birth weight is not sufficiently
      sensitive to discriminate subtler differences among population groups. The
      observed relationship between the neighborhoods' neonatal profile (particularly
      Apgar score and mode of delivery) and socioeconomic conditions shows evidence of
      a change in infant health profile, where the possibility for intervention shifts
      to medical services and the Apgar score assumes growing significance as a risk
      indicator.

PMID- 15868037
TI  - [Work-related accidents in traditional fishermen from the Medium Araguaia River
      region, Tocantins, Brazil].
AB  - This is a cross-sectional study of work-related accidents among traditional
      fishermen in the Medium Araguaia River region of Tocantins, Brazil. From June to
      August 2002, fishermen from the Municipality of Araguacema were interviewed about
      the organization of their work activities and work-related accidents during the
      previous six months. Of the 92 participating fishermen, 56 reported having
      suffered a work-related accident (annual incidence was 82.6%). Some 95.7% of
      those interviewed did not regularly pay social security insurance as self
      employed workers and were not aware of their social rights and duties. For
      fishermen reporting accidents, this proportion was 98.2%. Approximately 23.0% had
      another work activity, mainly as construction workers (47.6%) or sport-fishing
      guides (23.9%). Injuries inflicted by aquatic animals were the main form of
      accidents (about 86.0%). From these results, it is apparent that accidents from
      aquatic animals are an important health hazard, in some cases causing temporary
      work incapacity.

PMID- 15868038
TI  - [Pesticide poisoning in Dourados, Mato Grosso do Sul State, Brazil, 1992/2002].
AB  - Reports of poisoning and suicide attempts involving pesticides in the micro
      region of Dourados, Mato Grosso do Sul State, Brazil, from 1992 to 2002, were
      evaluated, using data from the Integrated Center for Toxicological Surveillance
      under the State Health Department. A total of 475 reports were made during the
      period, of which 261 were accidental or occupational poisonings, 203 suicide
      attempts, and 11 undetermined. Dourados county had the highest prevalence of
      pesticide poisoning and suicide attempts per 100,000 inhabitants, considering the
      rural population, and Fatima do Sul the second highest prevalence of suicides
      within the micro region. Significant correlations were found between poisoning
      and suicide (r = 0.60; p < 0.05) and between poisoning and temporary crop area as
      a percentage of the county's total area (r = 0.68; p < 0.05). Poisoning occurred
      predominantly in men (87.0%), but the percentage of suicide attempts by men and
      women were similar (53 and 47.0%, respectively). Poisonings occurred mostly from
      October to March and the organophosphate insecticides monocrotophos and
      methamidophos were the main pesticides involved.

PMID- 15868039
TI  - [Characteristics of traffic accidents and victims treated through a pre-hospital
      service in a city in southern Brazil, 1997/2000].
AB  - Traffic accidents and the resulting injury and trauma constitute an important
      social and public health problem. The objective of this study was to analyze the
      characteristics of such accidents and the victims treated by the only pre
      hospital service -- the Integrated Trauma and Emergency Aid Service (SIATE) -- in
      the city of Londrina, Parana State, southern Brazil, from 1997 to 2000. All
      victims (14,474) registered in the SIATE database were studied. The majority (>
      70.0%) were male and aged 10 to 39 years. Motorcyclists were the most frequent
      victims (> 40.0%), and accidents occurred most frequently in December, on
      weekends (especially Saturdays), and at night. These results are consistent with
      those of other studies showing the need to implement preventive measures
      targeting young males, especially motorcyclists.

PMID- 15868040
TI  - [Meningococcal disease: epidemiological profile in the Municipality of Manaus,
      Amazonas, Brazil, 1998/2002].
AB  - This epidemiological study focused on meningococcal meningitis in the
      Municipality of Manaus, Brazil from 1998 and 2002, considering the following
      aspects: incidence and case-fatality, age, sex, clinical manifestations,
      evolution, diagnostic criteria, and predominant meningococcal strains. The mean
      incidence rate for meningococcal meningitis in Manaus during the study period was
      7.8 cases per 100,000 inhabitants. The disease was more common in males. Infants
      (< 1 year age) were the most frequently affected age group. Mean case fatality
      was 14.0%. In 2002, serotype B meningococcus was the most prevalent (78.2%),
      while serotype C accounted for 7.2% of cases of meningococcal disease.

PMID- 15868041
TI  - Differences in self-rated health among older adults according to socioeconomic
      circumstances: the Bambui Health and Aging Study.
AB  - Self-rated health is influenced by socioeconomic circumstances, but related
      differences in its structure have received little attention. The objective of
      this study was to examine whether self-rated health structure differs according
      to socioeconomic circumstances in later life. The study included 1,505
      individuals (86.4%) residing in Bambui and aged 60 years or older. Correlates of
      self-rated health among lower-income older adults (monthly household income < USD
      240.00) and higher-income seniors were assessed. Social network stood out as a
      major factor in the structure of self-rated health among the poorest.
      Psychological distress was independently associated with worse self-rated health
      among the poorest, while perceptions by the wealthiest were broader, including
      psychological distress, insomnia, Trypanosoma cruzi infection, use of
      medications, and access to health services. Physician visits and hospitalizations
      were associated with self-rated health in both groups. Our results show important
      differences in the structure of self-rated health according to socioeconomic
      circumstances and reinforce the need for policies to reduce health inequalities
      in later life.

PMID- 15868042
TI  - [Homicides in Medellin, Colombia, from 1990 to 2002: victims, motives and
      circumstances].
AB  - In Medellin, Colombia, homicide has been the first cause of morbidity and
      mortality for 20 years. Medellin has the highest homicide rates of all major
      cities in Latin America. This study describes the victims, motives, and
      circumstances in homicides in Medellin from 1990 to 2002. The period included
      55,365 homicides, of which 1,394 were randomly studied. Of this sample, 93.6%
      (95%CI: 92.2%-94.8%) were males, 77.0% (95%CI: 75.0%-79.5%) less than 35 years of
      age, one-fourth had consumed alcohol, and nine out of ten were killed with
      firearms. The main motives were revenge and armed robbery. 37.0% (95%CI: 34.0%
      41.0%) of the victims lived in the lowest socioeconomic stratum of the city.
      Characteristics of homicides in Medellin have remained unchanged since the 1980s,
      when the most violent period in the city's history began. The most heavily
      affected groups are young males who live and die in poor neighborhoods, and the
      murders are individual acts that leave no wounded behind.

PMID- 15868043
TI  - [Hazardous alcohol use: screening and brief intervention as routine practice in
      primary care].
AB  - The variety of problems related to the so-called hazardous patterns of alcohol
      use make the latter a prominent public health concern. Screening instruments
      associated with brief interventions in primary care provide one of the frequently
      recommended secondary prevention strategies. The objective of this study was to
      assess the implementation of this strategy as a routine practice in primary
      health care services in the city of Juiz de Fora, Minas Gerais State, Brazil. A
      qualitative design was employed, including the application of semi-structured
      interviews for managers and health care professionals in the city's public health
      system, in addition to content analysis and participant observation. Results
      point to difficulties in the effective implementation of such routines both by
      managers and health care professionals. Health care professionals limit the
      approach to alcohol-dependent patients and demonstrate lack of motivation for
      preventive work. Health services managers experience difficulties in the
      organization and administration of such instruments, despite affirming their
      interest in the project.

PMID- 15868044
TI  - [Ethical conflicts in research with human subjects].
AB  - The Declaration of Helsinki (2000) helped trigger a major debate on many ethical
      aspects of research with human subjects. Topics under discussion include the use
      of placebos, the application of equipoise, the distinction between research
      ethics and clinical ethics, and the difference between therapeutic and non
      therapeutic trials. This article supports tenets that serve to protect patients
      involved in research, especially in those aspects concerning maintenance of best
      existing therapy, the rejection of using placebos, support of equipoise, the
      assurance that required medication shall be available beyond the termination of
      the research project, and that appropriate compensation will obtain to host
      communities inasmuch as they may have facilitated and supported the project. The
      current proposal of introducing a double ethical standard, aspirational for
      developed countries and pragmatic for poor nations, should be rejected, since it
      contravenes the universalizability of prescriptive ethics.

PMID- 15868045
TI  - [Prevalence and variables associated with leisure-time sedentary lifestyle in
      adults].
AB  - This study focused on the prevalence and determinants of leisure-time sedentary
      lifestyle in the city of Salvador, Bahia, Brazil. A cross-sectional design was
      used in a sample of 2,292 adults > or = 20 years of age, of whom 1,271 (55.0%)
      were females. Leisure-time sedentary lifestyle was defined by individuals who, in
      a live interview, stated that they performed no physical activity during their
      leisure time in a normal week. Initially, total prevalence of leisure-time
      sedentary lifestyle in the study population was calculated by variables
      associated and stratified by sex. Then, the prevalence ratio between leisure-time
      sedentary lifestyle, age, schooling, and marital status stratified by sex was
      calculated. A 95% confidence interval was used. Prevalence of leisure-time
      sedentary lifestyle was 72.5% and was more frequent in women 40-50 years of age
      and men over 60, individuals with limited schooling, and married, separated, and
      widowed individuals. The findings are relevant for public health, since they can
      be used both to identify high levels of leisure-time sedentary lifestyle in the
      Brazilian population as well as the determinants, thus allowing new intervention
      strategies to be implemented.

PMID- 15868046
TI  - [Entomological surveillance for Chagas disease in the mid-western region of Minas
      Gerais State, Brazil, from 2000 to 2003].
AB  - In Minas Gerais State, Brazil, after the elimination of Triatoma infestans by the
      Brazilian Chagas Disease Control Program, some triatomine species, such as
      Panstrongylus megistus, have merited the attention of entomological surveillance
      authorities. After the decentralization of the Brazilian health system, certain
      administrative and operational difficulties have been observed in some
      municipalities (counties). This study aims to evaluate entomological surveillance
      for Chagas disease in the 54 municipalities supervised by the Division of
      Decentralized Health Activities in Divinopolis, Minas Gerais, from 2000 to 2003.
      In 46 municipalities, 1,531 triatomines were captured, of which 94.1% were P.
      megistus. The infection rate for T. cruzi in the vectors was 1.3%. A total of 850
      reports were received and 835 site visits were conducted, showing that the
      program is active and efficient in the majority of the municipalities analyzed.
      The importance of the maintenance and improvement of entomological surveillance
      in the region was demonstrated, since triatomine bugs continue to invade (and can
      colonize) the domiciliary environment, although with low density.

PMID- 15868047
TI  - [The debate on lower back pain and its relationship to work: a retrospective
      study of workers on sick leave].
AB  - Lower back pain has a high prevalence among the Mexican working population, with
      extensive social and economic repercussions. Official figures show that lower
      back pain accounts for 10.0 to 15.0% of sick leave excuses. However, this fails
      to identify any relationship between lower back pain and job conditions, since
      such leave is only granted if it can be shown that the condition was not work
      related. The present study shows that such a relationship does in fact exist. A
      retrospective study examined all cases (n = 210) in which workers were granted
      sick leave for lower back pain in an IMSS (Mexican Government Health Insurance)
      hospital in Mexico City during a seven-year period. The results show the
      association and interactions between debilitating lower back pain and several
      work-related variables: job position, time-on-the-job, and physical effort and
      weight-carrying associated with the position. Causes of lower back pain and the
      difficulty in obtaining accurate, precise back pain diagnosis are discussed. A
      number of clinical, epidemiological, and legal strategies for the study and
      prevention of back pain are suggested.

PMID- 15868048
TI  - [Health surveillance and territory: theoretical and methodological
      possibilities].
AB  - Diagnoses of living conditions and health status, the constitutive elements for
      the reproduction of social life in various places, are listed and treated as
      contents disconnected from the territory. The recognition of social dynamics,
      habits, and customs is highly important for the determination of human health
      vulnerabilities, which originate in the interactions of social groups in given
      geographic spaces. The full use of the territory as a strategy for analyzing and
      intervening in health conditions presupposes the identification of geographic
      objects, their utilization by the population, and their importance for flows of
      persons and materials. It is thus necessary to develop methodologies for the
      recognition (both in the field and through secondary data) of objects and their
      forms, which are a condition for human action and existence. This article
      presents an approach to the incorporation of concepts from human geography in
      health practices, in light of two main authors: Milton Santos ("constitution of
      territory") and Anthony Giddens ("constitution of society").

PMID- 15868049
TI  - [Hip fracture incidence in an urban area in Northeast Brazil].
AB  - Hip fractures involve high morbidity and mortality and extensive treatment costs
      and are thus considered an important public health issue. Hip fracture incidence
      varies greatly between countries and even between cities in the same region. This
      study aimed to determine hip fracture incidence in Fortaleza, Ceara State,
      Brazil. Hip fracture cases were identified prospectively in patients aged 45 and
      over attending private and public hospitals in Fortaleza from July 2001 to June
      2002. The study identified 673 patients with hip fractures, 382 of whom from
      Fortaleza. Annual hip fracture incidence in Fortaleza for patients over 60 years
      was 21.7/10,000 inhabitants (13.0/10,000 for men and 27.7/10,000 for women). Hip
      fractures were more frequent among women and with advancing age. Hip fracture
      incidence in Fortaleza was very low compared to rates reported from other parts
      of the world.

PMID- 15868050
TI  - [Effects of violence and discrimination on the mental health of bisexuals,
      lesbians, and gays in Mexico City].
AB  - The objectives of this study were to estimate the prevalence of suicidal
      ideation, suicide attempts, mental disorders, and alcoholism in bisexuals,
      lesbians, and gays in Mexico City and analyze the possible relationship between
      violence, discrimination, and the mental health of these population groups. A
      questionnaire was administered to 506 bisexuals, lesbians, and gays attending
      support organizations and institutions. Eight forms of discrimination and
      fourteen forms of violence based on sexual orientation were researched. The study
      found the following prevalence rates: 39.0% suicidal ideation, 15.0% suicide
      attempts, 27.0% mental disorders, and 18.0% alcoholism. Prevalence of alcoholism
      was 21.0% among bisexual and lesbian women, which is higher than in other women.
      Discrimination was correlated with suicide attempts and mental disorders, whereas
      violence was a risk factor for suicidal ideation, suicide attempts, mental
      disorders, and alcoholism. Violence and to a lesser extent discrimination
      suffered by bisexuals, lesbians, and gays are associated with psychological
      distress, and policies are needed to counter this situation.

PMID- 15868051
TI  - Heterogeneous geographic distribution of human T-cell lymphotropic viruses I and
      II (HTLV-I/II): serological screening prevalence rates in blood donors from large
      urban areas in Brazil.
AB  - Brazil may have the highest absolute number of HTLV-I/II seropositive individuals
      in the world. Screening potential blood donors for HTLV-I/II is mandatory in
      Brazil. The public blood center network accounts for about 80.0% of all blood
      collected. We conducted a cross-sectional study to assess the geographic
      distribution of HTLV-I/II serological screening prevalence rates in blood donors
      from 27 large urban areas in the various States of Brazil, from 1995 to 2000.
      Enzyme immunoassay (EIA) was used to test for HTLV-I/II. The mean prevalence
      rates ranged from 0.4/1,000 in Florianopolis, capital of Santa Catarina State, in
      the South, to 10.0/1,000 in Sao Luiz, Maranhao State, in the Northeast. EIA
      prevalence rates are lower in the South and higher in the North and Northeast.
      The reasons for such heterogeneity may be multiple and need further studies.

PMID- 15868052
TI  - [Blood donation: a marketing perspective].
AB  - This paper emphasizes how marketing can make a difference in repeat donations by
      volunteer blood donors, since the greatest challenge for health institutions is
      to maintain and increase blood donation. In this context, understanding volunteer
      donors' motivations is highly important, and the studies reported here
      demonstrate that several variables are relevant to blood donation. The huge
      number of patients in need of blood transfusions and the lack of sufficient blood
      and blood products justify the interest in this study, considering both donors'
      and blood banks' perspectives. Moreover, recognition of the importance of actions
      and orientation for donors is fundamental for developing a marketing strategy. It
      is thus relevant for health institutions to identify donors' actual needs and
      wishes.

PMID- 15868054
TI  - What is urban in the contemporary world?
AB  - Central concepts of contemporary life such as politics, civilization, and
      citizenship derive from the city's form and social organization. The city
      expresses the socio-spatial division of labor, and Henri Lefebvre proposes to
      view its transformation within a continuum from the political city to the urban,
      whereby it completes its domination over the countryside. The city's
      transformation into the urban takes place when industry brings production (and
      the proletariat) into that space of power. The city, locus of surplus, power, and
      the fiesta, a privileged scenario for social reproduction, was subordinated to
      the industrial logic and underwent a dual process: its centrality imploded, and
      its outskirts exploded on surrounding areas through the urban fabric, bearing
      with it the seeds of the polis and civitas. The urban praxis, formerly restricted
      to the city, re-politicized social space as a whole. In Brazil, the urban has its
      origins in the military governments' centralizing and integrating policies,
      following Vargas's expansionism and Kubitschek's developmental interiorization
      (or occupation of the hinterlands). Today, urban-industrial processes impose
      themselves over virtually all social space, in contemporary extended
      urbanization.

PMID- 15868055
TI  - Perspectives on urban conditions and population health.
AB  - The majority of the world's population will live in cities in the next few years
      and the pace of urbanization worldwide will continue to accelerate over the
      coming decades. While the number of megacities is projected to increase, the
      largest population growth is expected to be in cities of less than one million
      people. Such a dramatic demographic shift can be expected to have an impact on
      population health. Although there has been historic interest in how city living
      affects health, a cogent framework that enables systematic study of urban health
      across time and place has yet to emerge. Four alternate but complementary
      approaches to the study of urban health today are presented (urban health
      penalty, urban health advantage, urban sprawl, and an integrative urban
      conditions model) followed by three key questions that may help guide the study
      and practice of urban health in coming decades.

PMID- 15868056
TI  - The urban environment from the health perspective: the case of Belo Horizonte,
      Minas Gerais, Brazil.
AB  - This study aims to determine spatial patterns of mortality and morbidity for five
      health problems in an urban environment: homicides, adolescent pregnancy, asthma
      hospitalization, and two vector-borne diseases, dengue and visceral
      leishmaniasis. All events were obtained through the city health database and
      geoprocessed using residential addresses and 80 planning units consisting of
      census tracts. We used thematic maps, proportionate mortality/morbidity ratios by
      planning unit, and the overlapped rank of the 20th worse planning unit rates for
      each event. A spatial pattern of high rates of homicides, proportion of young
      mothers, and hospitalization due to asthma overlapped in socially and
      economically disadvantaged areas. For the two vector-borne diseases, high rates
      with great dispersion were found in underprivileged areas, in contrast with very
      low rates among higher income areas. The results indicated the coexistence of
      heavier disease burden for residents of urban areas where poverty and lack of
      effective public health policies may be modulating social health problems. For
      the two vector-borne diseases, an environmental intervention in one mosquito
      borne disease might be playing a role in the other's incidence.

PMID- 15868057
TI  - [Determination of Entamoeba histolytica infection in patients from Greater
      Metropolitan Belem, Para, Brazil, by enzyme-linked immunosorbent assay (ELISA)
      for antigen detection].
AB  - The epidemiological status of amebiasis has been reevaluated since Entamoeba
      histolytica (pathogenic) was considered a distinct species from Entamoeba dispar
      (non-pathogenic). We investigated E. histolytica antigens in stool samples from
      residents of Belem, Para State, Brazil, with commercially available enzyme-linked
      immunosorbent assay (E. histolytica Test, TechLab Inc., Blacksburg, USA). A total
      of 845 samples were analyzed, of which 248 were positive (29.35%). E. histolytica
      infection was more frequent in the over-14-year age group (30.36%) than in the 0
      14-year group (28.28%), but the difference was not statistically significant (p <
      0.05). Of all the samples, 334 were also submitted to parasitological methods
      (direct, Hoffman, and Faust et al.). There were discordant results between ELISA
      and parasitological methods in 83 samples (24.85%), with more positive results
      using ELISA. Our results thus suggest that intestinal amebiasis is an important
      public health problem in Greater Metropolitan Belem.

PMID- 15868058
TI  - Risk factors for reinvasion of human dwellings by sylvatic triatomines in
      northern Bahia State, Brazil.
AB  - The aim of this study in Curaca, Bahia, Northeast Brazil was to explore possible
      factors associated with the infestation of human dwellings by Triatoma
      brasiliensis or Triatoma pseudomaculata, two sylvatic triatomine species. We use
      multiple logistic regression analysis to show how structural features of the
      peridomiciliary area combine with the number of animals and sociological factors
      to allow infestation of some dwellings. It is suggested that T. brasiliensis is
      associated with human activities, while T. pseudomaculata is associated with
      vegetation and animals. Peridomiciliary farm animals are a strong risk factor for
      triatomine infestation.

PMID- 15868059
TI  - [Social support scale: test-retest reliability in pregnant women and structures
      of agreement and disagreement].
AB  - There is a growing interest in research on the association between social support
      and health outcomes. The objective of this study was to evaluate the reliability
      and structure of agreement of a social support scale. Test-retest reliability was
      measured in a group of pregnant women (n = 65) in a public maternity ward.
      Intraclass correlation coefficient (ICC) and quadractically weighted kappa (kw2)
      were used as agreement measures. Log-linear statistical models were fitted to
      describe patterns of agreement. ICC for social support score was 0.90. The kw2
      ranged from 0.23 to 0.70. Log-linear models that provided the best fit to the
      data were diagonal agreement plus linear-by-linear association and quasi
      independence models. The scale was considered a reliable instrument to measure
      social support scale in low-income pregnant women.

PMID- 15868061
TI  - Evaluation of antioxidant properties of dermocosmetic creams by direct
      electrochemical measurements.
AB  - Cyclic voltammetry and linear sweep voltammetry were preliminarily used in order
      to evaluate the global antioxidant properties of dermocosmetic creams.
      Experiments were performed by introducing electrodes directly into the creams
      without any pretreatment of the samples. Current-potential curves showed
      significant anodic current depending on the antioxidant-containing cream studied.
      In comparison, little amperometric response was recorded with an antioxidant-free
      cream base. Aqueous solutions of the corresponding antioxidants showed analogous
      anodic waves and similar peak potentials. A correlation between the global anodic
      peak and the presence of the antioxidant species in the cream was made with
      eleven skin creams, attesting to the reliability of the method. Among the tested
      electrode materials, platinum gave the best results in terms of electrochemical
      kinetics and measurement precision (current peak standard deviation less than
      5%). Exposure of a depilatory cream to oxidizing agents (e.g., hydrogen peroxide,
      air, or light) caused a decrease in peak current as expected. This methodology
      enabled us to evaluate the evolution of the total antioxidant capacity under
      oxidative stress and gives encouragement to further development of a voltammetric
      method to quantify cream antioxidant power.

PMID- 15868062
TI  - Permeation study of five formulations of alpha-tocopherol acetate through human
      cadaver skin.
AB  - Alpha-tocopherol (AT) is the vitamin E homologue with the highest in vivo
      biological activity. AT protects against the carcinogenic and mutagenic activity
      of ionizing radiation and chemical agents, and possibly against UV-induced
      cutaneous damage. For stability consideration, alpha-tocopherol is usually used
      as its prodrug ester, alpha-tocopherol acetate (ATA), which once absorbed into
      the skin is hydrolyzed to alpha-tocopherol, the active form. The objective of
      this research was to characterize in vitro the permeation properties of ATA from
      various solutions and gel formulations. Permeation studies were conducted using
      modified Franz diffusion cells and human cadaver skin as the membrane.
      Specifically, 5% (w/w) alpha-tocopherol acetate was formulated in the following
      vehicles: ethanol, isopropyl myristate, light mineral oil, 1% Klucel gel in
      ethanol, and 3% Klucel gel in ethanol (w/w). The receiver temperature was 37
      degrees C. Samples from the receiver were collected at 2, 4, 6, 8, 12, 24, 30,
      36, and 48 hours and analyzed by HPLC for concentrations of alpha-tocopherol
      acetate and alpha-tocopherol. The permeabilities of ATA through human cadaver
      skin were 1.0x10(-4), 1.1x10(-2), 1.4x10(-4), 2.1x10(-4), and 4.7x10(-4) cm/h for
      the ethanol solution, isopropyl myristate solution, light mineral oil solution,
      1% Klucel gel, and 3% Klucel gel, respectively. The results show that the
      formulation had relatively minor effects on the permeability coefficients of ATA
      through cadaver skin in all cases except for the isopropyl myristate solution.

PMID- 15868063
TI  - Quantitative model of cellulite: three-dimensional skin surface topography,
      biophysical characterization, and relationship to human perception.
AB  - Gynoid lipodystrophy (cellulite) is the irregular, dimpled skin surface of the
      thighs, abdomen, and buttocks in 85% of post-adolescent women. The distinctive
      surface morphology is believed to result when subcutaneous adipose tissue
      protrudes into the lower reticular dermis, thereby creating irregularities at the
      surface. The biomechanical properties of epidermal and dermal tissue may also
      influence severity. Cellulite-affected thigh sites were measured in 51 females
      with varying degrees of cellulite, in 11 non-cellulite controls, and in 10 male
      controls. A non-contact high-resolution three-dimensional laser surface scanner
      was used to quantify the skin surface morphology and determine specific roughness
      values. The scans were evaluated by experts and naive judges (n=62). Body
      composition was evaluated via dual-energy x-ray absorptiometry; dermal thickness
      and the dermal-subcutaneous junction were evaluated via high-resolution 3D
      ultrasound and surface photography under compression. Biomechanical properties
      were also measured. The roughness parameters Svm (mean depth of the lowest
      valleys) and Sdr (ratio between the roughness surface area and the area of the xy
      plane) were highly correlated to the expert image grades and, therefore,
      designated as the quantitative measures of cellulite severity. The strength of
      the correlations among naive grades, expert grades, and roughness values
      confirmed that the data quantitatively evaluate the human perception of
      cellulite. Cellulite severity was correlated to BMI, thigh circumference, percent
      thigh fat, architecture of the dermal-subcutaneous border (ultrasound surface
      area, red-band SD from compressed images), compliance, and stiffness (negative
      correlation). Cellulite severity was predicted by the percent fat and the area of
      the dermal-subcutaneous border. The biomechanical properties did not
      significantly contribute to the prediction. Comparison of the parameters for
      females and males further suggest that percent thigh fat and surface area
      roughness deviation are the distinguishing features of cellulite.

PMID- 15868064
TI  - Reaction characteristics of a tooth-bleaching agent containing H2O2 and NaF: in
      vitro study of crystal structure change in treated hydroxyapatite and chemical
      states of incorporated fluorine.
AB  - This in vitro study was performed to elucidate the reaction mechanism of sodium
      fluoride (NaF), which is added to tooth-bleaching agents to lessen the adverse
      effect of hydrogen peroxide (H2O2) on teeth. Both hydroxyapatite (HAP) and
      dihydrated dicalcium phosphate (DCPD), model substances for dental hard tissues,
      dissolved easily in a simple H2O2 solution. In the H2O2/NaF solutions, however,
      fluorine compounds that could not be identified by X-ray diffraction (XRD) due to
      the smallness of the products were formed on the surface of the HAP. X-ray
      photoelectron spectroscopy (XPS) studies demonstrated that fluoridated
      hydroxyapatite (FHAP) was formed on HAP, and that calcium fluoride (CaF2)
      formation was accelerated by increasing the concentrations of fluorine and H2O2
      along with the partial dissolution of HAP. In H2O2/NaF solution, DCPD also
      transformed easily to FHAP and CaF2, which are favorable to the remineralization
      process on the tooth surface. Thus, the mechanism of NaF was elucidated, and its
      use together with H2O2 for tooth bleaching was proved to be effective.
      Methodologically, the XPS two-dimensional plot made it possible for the first
      time to directly estimate the ratio of FHAP and CaF2 in the reaction products, in
      contrast to the conventional wet-analytical method, which is simply based on the
      difference in solubility of the two components.

PMID- 15868065
TI  - Breast conservation after neoadjuvant chemotherapy.
AB  - BACKGROUND: Tumor downstaging by preoperative neoadjuvant chemotherapy in
      patients with locally advanced breast tumors allows breast conservation in women
      who were previously candidates for mastectomy. Nevertheless, lumpectomy success
      in such cases cannot be fully achieved. The aim of this study was to create a
      quantitative tool for preoperative evaluation of the success of breast
      conservation in such patients. METHODS: The study population included 100
      consecutive patients with stage II and III breast cancer who were designated for
      lumpectomy and 19 patients who were designated for mastectomy. All patients
      received neoadjuvant therapy. Breast-conserving surgery was offered in accordance
      with clinical and esthetic criteria. Demographic details and clinical, imaging,
      and pathologic information were collected from medical files. A decision protocol
      for classifying patients to lumpectomy or mastectomy was built by using the
      Classification and Regression Trees procedure based on preoperative
      characteristics. RESULTS: Three factors were found to be the main predictors for
      successful breast conservation: absence of diffuse microcalcifications as seen in
      the pretreatment mammogram, a postchemotherapy tumor size of < 25 mm, and the
      existence of a circumscribed lesion on mammography. CONCLUSIONS: The use of these
      criteria as a basis for decision on the type of surgery may decrease the
      performance of unnecessary procedures.

PMID- 15868066
TI  - Two types of classification for male opioid dependence: identification of an
      opioid addict with depressive features.
AB  - OBJECTIVE: There are similarities between alcoholics and opioid addicts and an
      overlap between both diagnostic groups. We tested the hypothesis that the type I
      and II classification, well established in male alcoholism, could also be
      relevant in a population of male opioid addicts. METHODS: A sample of 100
      hospitalized adult opioid dependent men were studied with the help of an extended
      semi-structured clinical interview, considering four classification criteria sets
      devised by Cloninger et al. (1981, 1982), von Knorring et al. (1985, 1987),
      Buydens-Branchey et al. (1989) and Babor et al. (1992). RESULTS: The two types of
      classification could be confirmed with all four criteria sets. In at least three
      of four analyses, 52 patients were allocated to the same larger cluster C1, and
      25 patients to a smaller cluster C2. These two groups were compared with each
      other with the help of the stepwise discriminant analysis. Seven variables were
      identified which excellently discriminate between the groups: The C2 patient is
      younger, has a history of therapy because of depression and a history of severe
      suicide attempts, also abuses benzodiazepines and becomes violent while
      intoxicated. His father suffers from alcoholism and received treatment because of
      depression. The C1 patient lacks these characteristics. CONCLUSIONS: The
      hypothesis was confirmed, showing that the two types of classification for male
      opioid addicts is feasible. A depressive type of male opioid dependent patient
      was identified. Early identification of patients of this type is clinically
      important.

PMID- 15868068
TI  - Non-adherence to aspirin or oral anticoagulants in secondary prevention after
      ischaemic stroke.
AB  - BACKGROUND: The effectiveness of medication is influenced by treatment adherence.
      After TIA or minor disabling stroke patients usually are advised to take
      antithrombotic medication. Stroke patients are an interesting group of patients
      with respect to adherence, since cardiovascular risk factors and stroke may
      (indirectly) negatively influence brain function, which can affect adherence. We
      investigated determinants of non-adherence in patients who used aspirin or oral
      anticoagulation after cerebral ischaemia of arterial origin. METHODS: Data of
      patients prospectively followed in two clinical trials (the Dutch TIA Trial and
      the Stroke Prevention In Reversible Ischaemia Trial) were analysed with Cox
      proportional hazards modelling. RESULTS: In the two trials 3796 patients were
      treated with aspirin. During a mean follow-up of 2.1 years, 689 patients (18%)
      prematurely stopped treatment, 305 (8 %) did so without a clear medical reason
      (non-adherence). Age >or= 65 years and the use of 300 instead of 30 mg of aspirin
      were independently associated with non-adherence. Diastolic blood pressure of
      >or= 90 mmHg and dizziness were associated with better adherence. Of 651 patients
      on oral anticoagulation, 143 patients (22 %) stopped after a mean follow-up of
      1.0 year, 66 (10 %) did so because of nonadherence. No statistically significant
      determinants for non-adherence were identified. CONCLUSION: As found in the
      literature on nonadherence in general, age of >or= 65 years and a higher dose of
      aspirin (300 mg versus 30 mg) were independently associated with non-adherence
      with aspirin treatment that was prescribed for secondary prevention after
      cerebral ischaemia of arterial origin. Older patients may require extra
      encouragement to continue antithrombotic treatment. Lower doses of aspirin may
      improve treatment adherence.

PMID- 15868067
TI  - Is dose escalation of antidepressants a rational strategy after a medium-dose
      treatment has failed? A systematic review.
AB  - BACKGROUND: Maximizing the dose of antidepressants is widely recommended in cases
      of non-response to medium-dose treatment. However, scientific evidence supporting
      high-dose treatment is scarce. Systematic studies comparing dose escalation with
      alternative strategies for refractory depression (i. e. augmentation or change of
      compound) are lacking. The aim of this publication is to review available direct
      and indirect evidence concerning dose increase of antidepressants after a medium
      dose trial has failed. METHOD: We performed a systematic literature search of
      Medline (1966-2003) and reviewed studies and publication references for available
      evidence. DATA SOURCES AND STUDY SELECTION: Studies of the following types were
      included: 1) dose increase studies in treatment refractory patients, 2)
      comparative dose studies, 3) therapeutic drug monitoring studies. RESULTS:
      Available data suggest differential efficacy of various pharmacological classes
      at more than medium-dosage. Direct evidence shows no increase of efficacy with
      high-dose selective serotonin reuptake inhibitor (SSRI) treatment; however,
      indirect evidence suggests enhanced therapeutic efficacy with high-dose tricyclic
      antidepressants. Few clinical data show ultra-high-dose treatment with the
      irreversible monoamine-oxidase-(MAO-) inhibitor tranylcypromine to be effective
      for refractory depression. Data concerning other selective compounds are
      insufficient to allow any definitive conclusion on the benefit of high-dose
      treatment. CONCLUSIONS: Based on available data highdose antidepressant treatment
      of patients refractory to medium-dose treatment is recommended for tricyclic
      compounds but not for SSRI. Some data suggest beneficial efficacy of ultra-high
      doses of the irreversible MAOI tranylcypromine. Research on other substance
      groups is limited and inconclusive. Prospective studies comparing dose escalation
      with alternative strategies for treatment of non-responding patients are needed.

PMID- 15868069
TI  - Metabolic characteristics of cortical malformations causing epilepsy.
AB  - PURPOSE: Cortical malformations (CMs) are increasingly recognized as the
      epileptogenic substrate in patients with medically refractory neocortical
      epilepsy (NE). The aim of this study was to test the hypotheses that: 1. CMs are
      metabolically heterogeneous. 2. The structurally normal appearing perilesional
      zone is characterized by similar metabolic abnormalities as the CM. METHODS:
      Magnetic resonance spectroscopic imaging (MRSI) in combination with tissue
      segmentation was performed on eight patients with NE and CMs and 19 age matched
      controls. In controls, NAA, Cr, Cho,NAA/Cr and NAA/Cho of all voxels of a given
      lobe were expressed as a function of white matter content and thresholds for
      pathological values determined by calculating the 95% prediction intervals. These
      thresholds were used to identify metabolically abnormal voxels within the CM and
      in the perilesional zone. RESULTS: 30% of all voxels in the CMs were abnormal,
      most frequently because of decreases of NAA or increases of Cho. Abnormal voxels
      tended to form metabolically heterogeneous clusters interspersed in metabolically
      normal regions. Furthermore, 15% of all voxels in the perilesional zone were
      abnormal, the most frequent being decreases of NAA and Cr. CONCLUSION: In CMs
      metabolically normal regions are interspersed with metabolically heterogeneous
      abnormal regions. Metabolic abnormalities in the perilesional zone share several
      characteristics of CMs and might therefore represent areas with microscopic
      malformations and/or intrinsic epileptogenicity.

PMID- 15868070
TI  - Remarks on quantitative ultrasound (QUS) and densitometric measurements.

PMID- 15868072
TI  - Response to novel housing in two groups of captive tufted capuchin monkeys (Cebus
      apella).
AB  - The influence of age, maternal status, and the presence of a group male on use of
      space was assessed in two groups of captive tufted capuchin monkeys that
      underwent a move from indoor housing to a larger outdoor facility. Both groups
      originally contained two adult males, but only one group retained a male after
      the move. Following the move, mothers spent less time on the ground when carrying
      their infants than they did when not carrying their infants. In the group with no
      male (1) individuals decreased time spent on the ground relative to pre-move
      levels, whereas no such difference was noted in the group with the male; (2)
      females spent more time carrying their infants than did females in the group with
      a male. In the group with the adult male, juveniles spent less time on the ground
      than did non-mother adult females, whereas no difference had existed prior to the
      move. Grooming rates dropped from pre-move to post-move, but the mean number of
      partners with which each animal was in contact increased. Measures of social
      behavior varied across post-move observation periods inversely to time spent on
      the ground. These results are consistent with the view that an individual's
      relative vulnerability influences behavioral conservatism in novel environments,
      and suggests a relatively profound role for males in promoting exploration of new
      space in this species.

PMID- 15868071
TI  - Identification of vertebral fractures: an update.
AB  - Osteoporotic vertebral fracture is associated with increased morbidity and
      mortality. As a powerful predictor of future fracture risk, the identification of
      vertebral fracture helps target individuals who will benefit from anti-fracture
      therapy. The identification of vertebral fractures is problematic because (1)
      "normal" radiological appearances in the spine vary greatly both among and within
      individuals; (2) "normal" vertebrae may exhibit misleading radiological
      appearances due to radiographic projection error; and (3) "abnormal" appearances
      due to non-fracture deformities and normal variants are common, but can be
      difficult to differentiate from true vertebral fracture. Various methods of
      vertebral fracture definition have been proposed, but there is no agreed gold
      standard. Quantitative methods of vertebral fracture definition are objective and
      reproducible, but the major limitation of these methods is their inability to
      differentiate between vertebral deformity and vertebral fracture. The qualitative
      visual approach draws on the expertise of the reader, but it is a subjective
      method with poor interobserver agreement. Semiquantitative assessment of
      vertebral fracture is a standardized visual method, which is commonly applied in
      research studies as a surrogate gold standard. This method is more objective and
      reproducible than a purely qualitative approach, but can be difficult to apply.
      The established methods focus primarily on the identification of "reduced" or
      short vertebral height as an indication of vertebral fracture, but this is also a
      feature of some non-fracture deformities and normal variants. A modified visual
      approach known as algorithm-based qualitative assessment of vertebral fracture
      (ABQ) has recently been introduced, and this focuses on radiological evidence of
      change at the vertebral endplate as the primary indicator of fracture.
      Preliminary testing of the ABQ method has produced promising results, but the
      method requires further evaluation. Vertebral imaging by means of dual energy X
      ray absorptiometry (DXA) scanner produces images of near-radiographic quality at
      a fraction of the radiation dose incurred by conventional radiography. There is
      growing interest in vertebral fracture assessment using this technique as a means
      of assessing a patient's fracture risk. Given the increasing availability of new
      technology and the importance of accurate diagnosis of vertebral fracture, there
      is an urgent need for better awareness of and training in the definition of
      vertebral fracture. Methods of vertebral fracture definition should be validated
      by testing the association with clinical outcomes of vertebral fracture, in
      particular the prediction of incident fractures.

PMID- 15868073
TI  - The selection of pancreatic reconstruction techniques gives rise to higher
      incidences of morbidity: results of the 30th Japan Pancreatic Surgery
      Questionnaire Survey on pancreatoduodenectomy in Japan.
AB  - BACKGROUND/PURPOSE: We aimed to determine the impact of the surgical strategy
      used for pancreatic reconstruction on morbidity after pancreatoduodenectomy (PD).
      METHODS: A questionnaire was sent to all surgeon members of the Japan Pancreatic
      Surgery Club in December 2002. RESULTS: We received 152 replies, and the data
      from all of them were used in the analysis. Thirty-six percent of the 152
      responders performed PD and selected from among two or more pancreatic
      reconstruction techniques (PRTs). PRT selection was used no more frequently in
      the high- and medium-hospital-volume institutions than in low-hospital-volume
      institutions (25% or 37% vs 35%). The incidence of both "all arterial hemorrhage"
      and "delayed arterial hemorrhage" after PD in the institutions that used multiple
      PRTs was significantly higher than that in the institutions where only a single
      PRT was used (4.2% vs 2.2%, and 3.3% vs 1.5%, respectively; P < 0.05). In the
      high- and medium-hospital-volume institutions, the incidence of all arterial
      hemorrhage after PD in the multiple-PRT institutions was significantly higher
      than that in the single-PRT institutions (4.0% vs 1.9%; P < 0.05). Furthermore,
      in the low-hospital-volume institutions, the incidence of delayed arterial
      hemorrhage, 7 or more days after PD, was clearly higher in the multiple-PRT
      institutions than in the single-PRT institutions (4.1% vs 1.4%; P = 0.056).
      Therefore, the hospital-case volumes of PD were distributed as practice-case
      volumes according to the PRT by the selection of PRTs, and PRT selection gave
      rise to higher incidences of morbidity as a result of pancreatic leakage after
      PD. CONCLUSIONS: The hospital-case-volume - better outcome relation for PD was
      attributable to expert pancreatic reconstruction skills that can be mastered only
      through frequent repetition.

PMID- 15868074
TI  - Gallstone pancreatitis: positive correlation between severe pancreatitis and
      passed stone.
AB  - BACKGROUND/PURPOSE: Little is known about whether the severity of pancreatitis
      depends upon persistent stone impaction or stone passage into the duodenum, and
      the role of endoscopic sphincterotomy (ES) has remained controversial. METHODS:
      This study reviewed our experience of 183 patients with gallstone pancreatitis,
      with special attention paid to the relationship between the severity of
      pancreatitis, the severity of coexisting biliary pathology, and the outcome.
      RESULTS: Sixteen patients (9%) had severe pancreatitis (SP) and the remaining 167
      (91%) had mild pancreatitis (MP). All of the SP patients had pancreatic necrosis,
      and 6 of them developed multiple organ failure (MOF). No SP patients had stones
      impacted at the papilla of Vater or persistent stones and purulent bile in the
      bile duct (severe cholangitis). Most SP patients (94%) had stones in the
      gallbladder alone, suggesting stone passage into the duodenum. Of the 167 MP
      patients, on the other hand, 58 (35%) had severe cholangitis. Four patients (25%)
      with SP died of MOF. There were four deaths in the MP group (2%) and all in
      patients with coexisting severe cholangitis, 2 of whom were in septic shock at
      the time of admission. CONCLUSIONS: None of the SP patients had severe
      cholangitis. The positive correlation between SP and passed stone suggests that
      early ES should not be advocated for SP patients. MP patients with coexisting
      severe cholangitis are likely to benefit from ES.

PMID- 15868075
TI  - Duodenum preservation in pancreatic head resection to maintain pancreatic
      exocrine function (determined by pancreatic function diagnostant test and
      cholecystokinin secretion).
AB  - BACKGROUND/PURPOSE: Organ-preserving surgery, such as pylorus-preserving
      pancreatoduodenectomy (PPPD), duodenum-preserving pancreatic head resection
      (DPPHR), or medial pancreatectomy (MP), is one of the recent advances in
      pancreatic surgery. There was a previous report that preservation of the duodenum
      maintained pancreatic function. However, concerning the resected pancreas,
      patients were divided into two groups; one group included pancreatic head
      resections such as Whipple, PPPD, and complete DPPHR, and the other group
      included MP that removed only the pancreatic neck and preserved the pancreatic
      head and distal pancreas. The present study was designed to clarify the
      significance of duodenum preservation, in comparison with duodenum removal, in
      patients with pancreatic head resection, in terms of pancreatic function,
      determined by a pancreatic function diagnostant (PFD) test and cholecystokinin
      (CCK) secretion. METHODS: The subjects were 61 patients (10 with Whipple, 41 with
      PPPD, and 10 with complete DPPHR). PFD tests and postprandial plasma CCK
      secretion were used for evaluation. RESULTS: There was a significant difference
      between pre- and postoperative PFD values in the patients who received Whipple or
      PPPD; however, there was no difference in those who had complete DPPHR.
      Concerning the postoperative PFD value, complete DPPHR was superior to Whipple
      and PPPD. Regarding postprandial CCK secretion, the pre- and postoperative values
      were significantly different in the patients with Whipple or PPPD, but there was
      no difference in those with complete DPPHR. Comparing the three kinds of
      operations, complete DPPHR was superior to the other two procedures in its
      maintenance of pancreatic function. There was the significant correlation between
      CCK and PFD in our patients in the Spearman Rank Correlation (P < 0.0029) and
      Fisher's r to z (P < 0.0058). CONCLUSIONS: When pre- and postoperative pancreatic
      exocrine function and postprandial CCK secretion were measured in patients with
      pancreatic head resection, it was found that preservation of the entire duodenum
      was an important factor for maintaining pancreatic function.

PMID- 15868076
TI  - Type IV-A choledochal cysts: a challenge.
AB  - BACKGROUND/PURPOSE: Type IV-A choledochal cysts are characterized by congenital
      cystic dilatation of the biliary tree extending to involve the intrahepatic
      biliary channels also. A single-center experience of the management of type IV-A
      choledochal cysts is presented. METHODS: Thirty-five out of 105 (33%) patients
      with choledochal cysts, who underwent surgery at a tertiary care center in
      northern India from January 1989 to December 2002, were found to have a type IV-A
      (Todani's classification) cyst. The mean age of the patients was 24 years (range,
      3 months to 60 years); 17 patients in the group were adults and 22 were females.
      Presenting features were abdominal pain, jaundice, cholangitis, and abdominal
      lump, in various combinations. RESULTS: Excision of the extrahepatic part of the
      cyst and a wide bilio-enteric anastomosis was achieved in 32 (91%) patients,
      while internal drainage of the cyst was necessitated in 3 patients, for technical
      reasons: collaterals due to portal hypertension (1 patient) and dense adhesions
      (2 patients). Six (17%) patients developed postoperative complications: 3 had
      bilio-enteric anastomosis leaks, with 2 requiring a percutaneous proximal biliary
      diversion; 2 had intraabdominal bleeds requiring re-exploration, and 1 had
      external pancreatic fistula that closed spontaneously. Follow-up information was
      available for 28 (80%) patients. Mean duration of follow up was 25 months
      (median, 12 months; range, 6 months to 9 years). Three patients required re
      operation, for anastomotic stricture (n = 2) and hepatolithiasis and recurrent
      cholangitis (n = 1) during follow up. CONCLUSIONS: Excision of the extrahepatic
      part of the cyst and drainage of the intrahepatic part by a wide hilar or
      subhilar anastomosis gave satisfactory results in the majority of patients with
      type IV-A choledochal cysts. Close long-term follow up of these patients is
      essential, because they are likely to present with complications related to the
      residual intrahepatic part of the disease.

PMID- 15868077
TI  - Right intrahepatic pseudocyst following acute pancreatitis: an unusual location
      after acute pancreatitis.
AB  - The location of a pseudocyst (PC) in the liver is an exceptional event, and
      intrahepatic PCs are mainly located in the left lobe. We report here a case of
      right intrahepatic PC following acute pancreatitis associated with cystic
      (aberrant pancreatic) dystrophy of the duodenal wall (CDDW) and chronic
      pancreatitis. Morphological assessment (ultrasound, computed tomography [CT]
      scan, and cholangio-magnetic resonance imaging [MRI]) revealed a 10-cm right
      intrahepatic collection and rupture of the main pancreatic duct. Percutaneous
      puncture permitted us to detect a high level of amylase in the collection,
      confirming the diagnosis of intrahepatic PC. Surgical drainage concomitant with
      pancreatico-duodenectomy for the treatment of CDDW resulted in disappearance of
      the collection. The mechanism involved in this patient was rupture of the
      pancreatic duct in the retroperitoneal cavity and erosion reaching the right
      hepatic parenchyma. Although intrahepatic PCs are rare, the diagnosis of
      intrahepatic PC complicating acute pancreatitis can be confirmed by a high level
      of amylase in the collection. Asymptomatic intrahepatic PCs can be treated
      conservatively, and symptomatic intrahepatic PCs can be managed either
      transcutaneously or surgically.

PMID- 15868078
TI  - Spontaneous rupture and hemorrhage of hepatic focal nodular hyperplasia in lobus
      caudatus.
AB  - In general, focal nodular hyperplasia lesions of the liver have a benign natural
      course; the majority of cases remain asymptomatic and complications are rare. We
      report a case of spontaneous rupture and hemorrhage of focal nodular hyperplasia,
      which is extremely rare in the literature. A 35-year-old woman was admitted with
      severe upper abdominal pain and unstable hemodynamic status. No major abdominal
      trauma was noted. Radiology findings suggested a diffuse hemoperitoneum. Emergent
      surgical exploration showed a hemoperitoneum due to the rupture of a hepatic mass
      lesion in segment I. Suture of the rupture was undertaken with success. After
      this lifesaving emergent surgery, further investigations, including ultrasound,
      contrast-enhanced computed tomography, and magnetic resonance imaging, were
      undertaken, and a 5.7 x 9.8 x 6.4-cm focal nodular hyperplasia lesion was
      identified in segment I. Two weeks after the first surgical hemostasis, surgical
      removal of segment I, including the mass, was performed. The postoperative course
      was uneventful. Pathological evaluation confirmed the nature of focal nodular
      hyperplasia. The patient remains asymptomatic without evidence of recurrence 3
      years and 6 months after surgery. To our knowledge, this is the firstcase of
      spontaneous rupture and hemorrhage of focal nodular hyperplasia that needed two
      consecutive surgical operations.

PMID- 15868079
TI  - Parapapillary choledochoduodenal fistula associated with cholangiocarcinoma.
AB  - Parapapillary choledochoduodenal fistula is a rare disorder. We herein report a
      case of parapapillary choledochoduodenal fistula associated with
      cholangiocarcinoma. A 61-year-old woman was admitted to our hospital for further
      examination of a liver tumor. She had no clinical symptoms, but computed
      tomography scans showed an irregularly contoured liver tumor which was
      histologically confirmed to be adenocarcinoma, by a needle biopsy examination.
      Duodenal fiberscopy revealed a fistula orifice 1.0 cm proximal to the orifice of
      the papilla of Vater, and endoscopic retrograde cholangiography through the
      fistula showed a communication to the common bile duct. Hypotonic duodenography
      demonstrated reflux of contrast material into the choledochoduodenal fistula. The
      bile sample collected from the common bile duct showed extremely high levels of
      pancreatic enzymes, including amylase, phospholipase-A2, and elastase-I.
      Furthermore, Helicobacter DNA was detected in bile by polymerase chain reaction
      (PCR) analysis. This experience suggests to us that parapapillary
      choledochoduodenal fistula may be a risk factor for biliary tract carcinoma, and
      surgical management is the treatment of choice for this rare condition, even when
      the patient has no significant clinical symptoms.

PMID- 15868080
TI  - Long-term survival of a patient with advanced adenosquamous carcinoma of the
      gallbladder after radical resection.
AB  - Patients with adenosquamous carcinoma of the gallbladder tend to present with a
      bulky tumor that frequently displays involvement with adjacent organs, and
      diagnosis is usually made at an advanced stage. This may contribute to the poor
      prognosis of patients with adenosquamous carcinoma of the gallbladder compared to
      patients with adenocarcinoma. We present herein a patient with advanced
      adenosquamous carcinoma of the gallbladder who is doing well with no evidence of
      recurrence more than 5 years after radical resection. A 72-year-old woman
      complaining of generalized fatigue and loss of appetite was referred to our
      hospital with suspected cholelithiasis, following ultrasonography done at another
      hospital. On admission, abdominal ultrasonography and computed tomography
      revealed an irregularly shaped solid mass extending from the fundus of the
      gallbladder, and invasion of the stomach was strongly suspected. Gallbladder
      carcinoma was diagnosed, and radical resection, including partial gastrectomy,
      was performed. Histopathologically, adenosquamous carcinoma was diagnosed, and it
      was graded as si, hinf0, binf0, pv0, a0, t4, n0, and stage IVa.

PMID- 15868081
TI  - Primary sclerosing cholangitis in which differential diagnosis from gallbladder
      carcinoma was difficult.
AB  - We report a case of localized primary sclerosing cholangitis (PSC) which was
      difficult to distinguish from gallbladder carcinoma. A 75-year-old woman with
      elevated serum bilirubin was hospitalized and underwent endoscopic nasobiliary
      drainage (ENBD). There was no history of diseases such as gallbladder stone,
      pancreatitis, or ulcerative colitis. Cholangiography through the ENBD tube showed
      localized stenosis of the common bile duct; the gallbladder could not be seen.
      Angiography showed no encasement of the hepatic artery. Ultrasonography showed a
      tumor in the cystic duct, and the tumor had invaded the gallbladder and common
      bile duct. We diagnosed gallbladder carcinoma on radioimaging, and performed an
      S4aS5 subsegmentectomy of the liver and resection of the extrahepatic biliary
      tree. Pathologically, no malignant cells were detected, and fibrosis around bile
      ducts and infiltration of inflammatory cells into hepatic tissue were found. It
      is well known that PSC is sometimes difficult to differentially diagnose from
      cholangiocarcinoma. Our case is of high interest because ultrasonography showed
      findings suggestive of gallbladder carcinoma. It is therefore necessary to keep
      the possibility of PSC in mind for the diagnosis and treatment of such localized
      biliary stenosis.

PMID- 15868082
TI  - Hepatic resection of giant metastatic tumor from clear cell carcinoma of the
      ovary.
AB  - All cancer patients, particularly those treated for colorectal cancer, should be
      monitored for the presence of liver metastases, but liver metastases from ovarian
      clear cell carcinoma are quite rare. We report a patient subjected to extended
      left hepatectomy due to a giant metastasis 5 years after surgical treatment for
      an ovarian neoplasm that was histopathologically diagnosed as clear cell
      carcinoma. A 58-year-old woman had undergone hysterectomy and bilateral salpingo
      oophorectomy due to ovarian cancer (stage Ic). Four years and 8 months after the
      operation, a computed tomography (CT) scan demonstrated a giant tumor in the left
      lobe of the liver. The tumor compressed the inferior vena cava (IVC), but it was
      not clear whether it invaded the vessel. She received chemotherapy for 4 months;
      however, the tumor did not decrease in size. She was subsequently referred to our
      institution and was submitted to operation after it was confirmed that there were
      no distant metastases. After being subjected to an extended left hepatectomy and
      cholecystectomy, the patient recovered from the surgery without any
      complications. She has been carefully followed for 17 months and has presented no
      evidence of recurrence.

PMID- 15868083
TI  - Mirizzi syndrome secondary to an adenoma of the cystic duct.
AB  - Bile duct adenomas are uncommon lesions that can cause obstructive jaundice. We
      report the unusual case of a 54-year-old man who developed Mirizzi syndrome
      secondary to a bile duct papillary adenoma located in the cystic duct remnant. A
      case report is presented, together with a review of extrahepatic bile duct
      adenomas published in the English-language literature, with special attention
      directed toward the clinical manifestations, locations, and prognosis of these
      tumors. Bile duct adenomas are very rare tumors. Although cholangiography can
      detect many of these lesions, few cases were correctly diagnosed preoperatively.
      Most lesions were located in the distal common bile duct or at the ampulla of
      Vater. Pathologic examination often revealed foci of carcinoma in situ,
      dysplasia, or atypia. Local resection was performed in most cases. There were no
      previous case reports of extrinsic common bile duct obstruction caused by tumors
      within the cystic duct. We describe here a very rare, acalculous variant of
      Mirizzi syndrome secondary to a solitary papillary adenoma of the cystic duct. In
      general, bile duct adenomas are uncommon lesions that are difficult to diagnoses
      preoperatively. These tumors usually present with jaundice secondary to
      intraluminal biliary obstruction. These lesions are premalignant and should be
      managed by complete surgical resection.

PMID- 15868084
TI  - Telerobotic-assisted laparoscopic cholecystectomy: our experience on 29 patients.
AB  - BACKGROUND/PURPOSE: The role of computer-assisted surgery (CAS) is still debated
      and not clearly defined. METHODS: The authors report their initial experience
      with CAS, comparing 29 patients submitted to cholecystectomy, using a Zeus remote
      controlled robot and an Aesop remote voice-activated endoscope robot, with 29
      patients submitted to standard laparoscopic cholecystectomy (LC). The surgical
      field and the arms of the robot were under the direct and real-time control of
      the surgeon, who stayed at the workstation and maneuvered the Zeus, using
      joysticks. The workstation was in the same room as the patient. RESULTS: Twenty
      nine patients underwent telerobotic-assisted cholecystectomy (TLAC); 1 procedure
      was converted to standard LC and 1 to open cholecystectomy. The conversions were
      due to choledocholithiasis and cholecystitis. During TLAC, the mean operating
      time and transition time (from the induction of anesthesia to incision of the
      skin) were, respectively, 75 min (range, 60-170 min) and 45 min (range, 25-60
      min). We did not observe any complications related to TLAC. The limitations of
      TLAC were the lack of tactile feedback, the increase in surgical time, and the
      expensive cost of the procedure to reach the same result as that of LC.
      CONCLUSIONS: After this initial experience, we believe that TLAC could be
      considered only for training in CAS, but that it is without advantages in terms
      of its higher cost compared with LC.

PMID- 15868085
TI  - Robotic-assisted laparoscopic Roux-en-Y choledochojejunostomy in pigs.
AB  - BACKGROUND/PURPOSE: We aimed to investigate the feasibility of robotic-assisted
      laparascopic reconstruction of the common bile duct (CBD) by way of Roux-en-Y
      choledochojejunostomy, given an operator with no prior robotic skills. METHODS:
      Ten pigs, of 75 kg median weight, were used for the experiments. Three of these
      animals were used to initialize and adjust the procedure, and seven were
      scheduled for postoperative survival of a week, and subsequent laparotomy for
      evaluation. The gallbladder was removed and a Roux-en-Y choledochojejunostomy was
      done. Blood samples were drawn prior to the first and the final operation. Under
      laparotomy, the animals were investigated for signs of cholascos and
      intraoperative cholangiography was performed. RESULTS: All pigs showed competent
      anastomoses upon evaluation, including two pigs, which died on the fourth and
      fifth postoperative days, respectively, due to incorrect suspension of the Roux
      en-Y sling, resulting in gastric retention. Standard liver parameters were not
      affected by surgery, and cholangiography showed no signs of extrahepatic stenosis
      or intrahepatic dilatation. CONCLUSIONS: Robotic-assisted Roux-en-Y choledocho
      jejunostomy is an easy procedure and accomplishes biliary drainage and intact
      intestinal flow. Decreasing operating times were experienced, approximating those
      of a skilled operator.

PMID- 15868086
TI  - Preservation of collateral pathways during pancreaticoduodenectomy in case of
      celiac axis occlusion.

PMID- 15868095
TI  - Identification of previously unknown antigenic epitopes on the S and N proteins
      of avian infectious bronchitis virus.
AB  - This paper describes mapping of antigenic and host-protective epitopes of
      infectious bronchitis virus proteins by assessing the ability of defined peptide
      regions within the S1, S2 and N proteins to elicit humoral, cell-mediated and
      protective immune responses. Peptides corresponding to six regions in the S1 (Sp1
      Sp6), one in the S2 (Sp7) and four in the N protein (Np1-Np4) were synthesized
      and coupled to either diphtheria toxoid (dt) or biotin (bt). Bt-peptides were
      used to assess if selected regions were antigenic and contained B- or T-cell
      epitopes and dt-peptides if regions induced an antibody response and protection
      against virulent challenge. All S1 and S2 peptides were antigenic, being
      recognised by IBV immune sera and also induced an antibody response following
      inoculation into chicks. Three S1-and one S2-bt peptides also induced a delayed
      type hypersensitivity response indicating the presence of T-cell epitopes. The S2
      peptide Sp7 (amino acid position 566-584) previously identified as an
      immundominant region, was the most antigenic of all peptides used in this study.
      Two S1 (Sp4 and Sp6) and one S2 peptide (Sp7), protected kidney tissue against
      virulent challenge. From four N peptides located in the amino-terminal part of
      the N protein, only one, Np2 (amino acid position 72-86), was antigenic and also
      induced a delayed type hypersensitivity response. None of the N peptides induced
      protection against virulent challenge. The results suggest that the S1
      glycoprotein carries additional antigenic regions to those previously identified
      and that two regions located in the S1 and one in the S2 at amino acid positions
      294-316 (Sp4), 532-537 (Sp6) and 566-584 (Sp7) may have a role in protection.

PMID- 15868096
TI  - Preparation of immunoblot test stripes from a Rubella virus-like particles dye
      crystal complex as antigen.
AB  - Stably transfected Chinese hamster ovary (CHO24S) cells were the source for
      Rubella virus-like particles (RVLP) containing all structural proteins (E1, E2, C
      and their dimers). RVLP are secreted from the CHO24S cells into the medium and
      the time-point for collecting the medium with the highest yield of >100 kDa
      proteins (with 17 mg protein from 10 ml cell culture supernatant) was after 2
      days of incubation. Different methods for RVLP isolation from the cell culture
      supernatants were assessed by SDS-PAGE and Western blotting (using sera positive
      or negative for Rubella virus (RV)-specific antibodies or an anti-E1 monoclonal
      antibody). A combination of membrane filtration with a rapid, novel gradient
      ultracentrifugation step (using Coomassie brilliant blue G crystals as adsorbens
      for RVLP that facilitated virus isolation) was the most suitable technique. 132
      RV-positive human sera (RV IgG > 20 IU/ml by commercial ELISA) were tested by our
      "self made" immunoblot test stripes (using RVLP adsorbed to dye crystals as
      antigen) for the presence or absence of antibodies specific for RV structural
      proteins. 57.6% of these sera had antibodies against E1, E2 and C, 31% against E1
      and C, and 1.5% against E1 only, whereas 3.8% had no RV specific antibodies and
      only 6.0% were equivocal which demonstrated that these "self made" test stripes
      can reliably differentiate RV antibody specificities.

PMID- 15868097
TI  - Effects of baculovirus transactivators IE-1 and IE-2 on the Drosophila heat shock
      70 promoter in two insect cell lines.
AB  - Baculovirus infection of permissive cells proceeds in a cascade fashion with the
      transcription of early, late and very late genes. The structure of a number of
      baculovirus early gene promoters has been dissected in detail and the viral
      factors necessary to stimulate their expression have been identified. Early
      baculovirus gene promoters in general have a resemblance to host promoters while
      late and very late gene promoters are different from early baculovirus promoters
      and are more defined. In this study we investigated whether two key Autographa
      californica M nucleopolyhedrovirus (AcMNPV) transactivators have the ability to
      regulate the commonly used cellular promoter from the Drosophila heat shock 70
      protein gene, during transient gene expression assays in two insect cell lines
      permissive for AcMNPV infection, SF-21 and TN-368, or during viral infection. The
      AcMNPV ie-1 transactivator gene stimulated gene expression of this cellular
      promoter in both cell lines when the promoter was cis-linked to an enhancer
      element, but stimulation in the absence of enhancer elements was either
      undetected or lower than in the presence of enhancer elements in SF-21 and TN-368
      cells, respectively. The transactivator ie-2 stimulated gene expression in the
      presence of cis-linked enhancer elements and ie-1 in SF-21 cells. During viral
      infection, the heat shock 70 promoter was maximally activated at 12 hours post
      infection. We discuss how these results affect the interpretation of transient
      gene expression assays performed in the presence of viral transcription factors.

PMID- 15868098
TI  - The use of virtual fluoroscopy in managing acute type II odontoid fracture with
      anterior single-screw fixation. A safe, effective, elegant and fast form of
      treatment.
AB  - BACKGROUND: The management of odontoid fractures represents both a clinical and a
      technical challenge due to the singular anatomy and biomechanics of the region.
      At present there is still much controversy as far as any form of management
      (surgical vs. conservative) is concerned and in any case there is not sufficient
      evidence to support a standardized form of treatment. This study was designed to
      further evaluate safety and efficacy of anterior odontoid single-screw fixation
      and to better determine the usefulness of Image Guided Surgery Virtual
      Fluoroscopy in treating such cases assessing also its advantages over traditional
      fluoroscopy and CT-guided frameless stereotaxy in the upper cervical spine
      surgery. METHODS: This was a retrospective review of ten patients presented
      during a short period of 18 months with acute traumatic Type II odontoid
      fractures. Nine underwent fixation within a mean of 3 days after injury, whereas
      a patient had to be operated upon on the 22nd day due to poor alignment with
      conservative treatment and ongoing instability. All patients postoperatively were
      fitted in a collar and then followed-up with serial clinical and radiographic
      examinations. FINDINGS: Radiological signs of fusion were seen in 10 cases (100%)
      (mean follow-up: 16 months). No complications occurred during the surgical
      procedure, nor were any instrumentation failures recorded; all patients remained
      neurologically intact. CONCLUSIONS: We believe that anterior odontoid screw
      fixation using Image Guided Surgery virtual fluoroscopy is a safe, effective,
      less time consuming and low x-ray exposure technique and we recommend this as the
      preferred treatment method for acute Type II odontoid fractures. Moreover, the
      use of image guided technology affords more precision, confidence and safety
      enabling the surgeon to approach the upper cervical spine in an easier and faster
      way.

PMID- 15868099
TI  - Actin polymerization machinery: the finish line of signaling networks, the
      starting point of cellular movement.
AB  - Dynamic assembly of actin filaments generates the forces supporting cell
      motility. Several recent biochemical and genetic studies have revealed a plethora
      of different actin binding proteins whose coordinated activity regulates the
      turnover of actin filaments, thus controlling a variety of actin-based processes,
      including cell migration. Additionally, emerging evidence is highlighting a
      scenario whereby the same basic set of actin regulatory proteins is also the
      convergent node of different signaling pathways emanating from extracellular
      stimuli, like those from receptor tyrosine kinases. Here, we will focus on the
      molecular mechanisms of how the machinery of actin polymerization functions and
      is regulated, in a signaling-dependent mode, to generate site-directed actin
      assembly leading to cell motility.

PMID- 15868100
TI  - Membrane translocation and oligomerization of hBok are triggered in response to
      apoptotic stimuli and Bnip3.
AB  - hBok is a human pro-apoptotic member of the Bcl-2 family. By fluorescence in situ
      hybridization and in silico analysis, hBok was found to be located on chromosome
      2q37.3. Its expression was detected in various organs and several hormonally
      regulated cancer cells. Expression of hBok was shown to be upregulated in
      estrogen-dependent breast cancer by estrogen deprivation and in myocardial cells
      during hypoxia. Confocal laser scanning microscopy examinations and subcellular
      fractionation studies showed that hBok was distributed in both the cytosol and
      intracellular membranes of healthy cells. Upon overexpression of hBok or
      stimulation of apoptosis, hBok became integrated into the membrane. Furthermore,
      apoptosis and oligomerization were promoted by BH3-only proteins, such as Bid,
      Bnip3 and p53, but prevented by BFL-1. hBok was found to interact with Bnip3. Our
      findings suggest that functional BH3-only proteins facilite the oligomerization
      and insertion of hBok into the membrane to activate it.

PMID- 15868101
TI  - Modeling the MHC class I pathway by combining predictions of proteasomal
      cleavage, TAP transport and MHC class I binding.
AB  - Epitopes presented by major histocompatibility complex (MHC) class I molecules
      are selected by a multi-step process. Here we present the first computational
      prediction of this process based on in vitro experiments characterizing
      proteasomal cleavage, transport by the transporter associated with antigen
      processing (TAP) and MHC class I binding. Our novel prediction method for
      proteasomal cleavages outperforms existing methods when tested on in vitro
      cleavage data. The analysis of our predictions for a new dataset consisting of
      390 endogenously processed MHC class I ligands from cells with known proteasome
      composition shows that the immunological advantage of switching from constitutive
      to immunoproteasomes is mainly to suppress the creation of peptides in the
      cytosol that TAP cannot transport. Furthermore, we show that proteasomes are
      unlikely to generate MHC class I ligands with a C-terminal lysine residue,
      suggesting processing of these ligands by a different protease that may be
      tripeptidyl-peptidase II (TPPII).

PMID- 15868103
TI  - Elucidation of the relationship between enzyme activity and internal motion using
      a lysozyme stabilized by cavity-filling mutations.
AB  - We investigated the activity and the internal motions of a stabilized mutant hen
      lysozyme (HEL) in which the residues M12 and L56 were mutated to L and F,
      respectively (LF mutant HEL). The result of the activity measurements against
      glycol chitin at various temperatures suggested that the temperature dependence
      of the activity of LF mutant HEL shifted to the high-temperature side compared
      with that of wild-type HEL. The detailed internal motions of LF mutant HEL in the
      absence and presence of a substrate analogue, (NAG)3, were examined by model-free
      analysis at 35 degrees C. The results showed that the internal motions of LF
      mutant HEL in the presence of (NAG)3 were drastically restricted compared with
      those in wild-type HEL. Our findings thus suggested that the mutation to the
      stabilized lysozyme restricted internal motions required for the enzymatic
      reaction.

PMID- 15868102
TI  - Structural organization and cellular localization of tuftelin-interacting protein
      11 (TFIP11).
AB  - Tuftelin-interacting protein (TFIP11) was first identified in a yeast two-hybrid
      screening as a protein interacting with tuftelin. The ubiquitous expression of
      TFIP11 suggested that it might have other functions in non-dental tissues. TFIP11
      contains a G-patch, a protein domain believed to be involved in RNA binding.
      Using a green fluorescence protein tag, TFIP11 was found to locate in a novel
      subnuclear structure that we refer to as the TFIP body. An in vivo splicing assay
      demonstrated that TFIP11 is a novel splicing factor. TFIP11 diffuses from the
      TFIP body following RNase A treatment, suggesting that the retention of TFIP11 is
      RNA dependent. RNA polymerase II inhibitor (-amanitin and actinomycin D)
      treatment causes enlargement in size and decrease in number of TFIP bodies,
      suggesting that TFIP bodies perform a storage function rather than an active
      splicing function. The TFIP body may therefore represent a new subnuclear storage
      compartment for splicing components.

PMID- 15868107
TI  - Long-term interactive group education for type 1 diabetic patients.
AB  - The aim of this study was to assess the feasibility and efficacy of an
      Interactive Educational and Support Group programme (IESG) for patients with type
      1 diabetes. A sample of 96 type 1 diabetic outpatients was studied measuring the
      effects of participation in IEGS on metabolic control and diabetes-related
      quality of life (QoL). Those refusing to participate (n = 48) and a sample of 37
      patients who were not invited to IESG (control) where studied for comparison.
      After one year, participants showed a significant (p < 0.05) improvement of
      HbA(1c) from 7.7+/-1.6 to 7.2+/-1.5%, whereas no variation of HbA(1c) was
      observed in non-participants and controls. No significant variation of QoL was
      observed in any of the three groups. At two-years follow-up, HbA(1c) of the
      patients attending IESG was not significantly different from that at one-year
      follow-up, and it was significantly lower than that observed at enrolment. QoL
      showed a significant improvement at 2 years with respect to baseline and one-year
      follow-up. In conclusion, this programme appears to be effective in the
      improvement of medium term metabolic control and QoL.

PMID- 15868108
TI  - Autonomic, endothelial function and the analysis of gait in patients with type 1
      and type 2 diabetes.
AB  - Ten control subjects and 20 subjects with type 1 and type 2 diabetes were
      examined to compare autonomic, endothelial function and gait characteristics
      while walking in a linear path and during turns. To measure deviations in gait,
      timing was recorded from foot sensors worn in the shoes and from accelerometers
      (2 axis) mounted on the head, shoulder, hips, knees and ankles, bilaterally. The
      results of the experiments showed that subjects with diabetes took additional
      steps when walking in a linear path and during turns. They also took
      significantly more time to walk a given distance (greater than 30%) than control
      subjects. Accelerometry data also revealed that there was an increase in
      flexion/extension and lateral movement at the major joints in the body. Joint
      movements at the hip, knee, ankle and shoulders showed a 50 and 100% increase in
      movement at the joints during gait for subjects with diabetes compared to control
      subjects. These findings suggest that individuals with type 1 and type 2 diabetes
      can have significant problems in both the timing and quality of gait. These
      impairments are likely secondary to dysfunction of the vestibular, somatosensory
      and autonomic system in diabetics. Data here showed at least a 50% impairment in
      local tissue blood flow and autonomic function in subjects in both type 1 and
      type 2 diabetes compared to control subjects.

PMID- 15868109
TI  - Effect of hyperglycaemic load on maternal-foetal transport of L-leucine in
      perfused human placental lobule: in vitro study.
AB  - The effect of hyperglycaemic loads on L-leucine transport in the maternal-foetal
      direction has been investigated in human placenta in vitro, using perfusion of
      isolated placental lobules. National Culture and Tissue Collection medium diluted
      with Earle's buffered salt solution was used as the perfusate. (14)C-labelled L
      leucine along with tritiated water as reference were injected as a 100-microl
      bolus into the maternal circulation and serial perfusate samples were collected
      over a 5-min study period. In 6 successful perfusions, the differential transport
      rate of leucine for 10, 25, 50, 75 and 90% of efflux in the foetal vein averaged
      1.26, 1.10, 1.19, 1.10 and 1.04 times respectively that of reference in the
      control euglycaemic phase. In the experimental hyperglycaemic phases of 27.8 and
      55.6 mM/l, leucine transport for the corresponding efflux periods averaged 1.37,
      1.33, 1.28, 1.22 and 1.26 times and 1.16, 0.97, 1.08, 1.08 and 1.08 times
      respectively that of the reference marker. Analysis of variance (ANOVA) test
      showed that the difference between the three groups was not statistically
      significant. In the control euglycaemic phase, leucine transport fraction (TF)
      averaged 40.90+/-3.51% of corresponding water TF while in experimental
      hyperglycaemic phases, TF of the amino acid averaged 37.80+/-4.82% and 35.61+/
      3.21% of water TF respectively. The difference between the control and
      hyperglycaemic perfusion phases was not statistically significant. Further, no
      statistical difference could be shown between the two hyperglycaemic perfusion
      series themselves. Similarly, kinetic parameters such as absorption rate,
      elimination rate and absorption rate:elimination rate ratio were not
      significantly different in the hyperglycaemic perfusion phases compared to
      control phase. Our studies seem to indicate that leucine transport kinetics in in
      vitro conditions are not altered significantly in placentas exposed to
      hyperglycaemic loads.

PMID- 15868110
TI  - Macrophage-derived cytokine and nitric oxide profiles in type I and type II
      diabetes mellitus: effect of thymoquinone.
AB  - Comparing macrophage-derived cytokine and nitric oxide (NO) profiles in type I
      and type II diabetes mellitus (DM); and determining whether thymoquinone (TQ) has
      any modulatory effect were the main objectives of the present study. Peritoneal
      macrophages have been collected from Otsuka Long-Evans Tokushima Fatty (OLETF) as
      a model for type II DM and its control Long-Evans Tokushima Otsuka (LETO) rats,
      as well as from streptozotocin (STZ)-injected LETO ones as a model for type I DM.
      The cells were cultured and incubated with or without TQ (10 microM) in the
      absence or presence of lipopolysaccharide (LPS; 1 microg/ml). The same parameters
      have been also assessed in sera of the used animals with or without TQ treatment
      (3 mg/kg) under both LPS-stimulated (10 mg/kg) and unstimulated conditions.
      Nitrite, IL-1beta and TNF-alpha were significantly higher in macrophage
      supernatants and sera of the acutely affected STZ-LETO rats either with or
      without LPS stimulation compared to corresponding controls. On the other hand,
      chronically diabetic OLETF rats' macrophage supernatants showed significant
      decreases of IL-1beta and TNF-alpha levels upon LPS stimulation or even without
      stimulation (IL-1beta); and insignificant increase in nitrite concentration,
      which turned significant upon LPS stimulation. Sera of these animals, however,
      showed significant increase in TNF-alpha level. TQ normalised the elevated
      nitrite and cytokine profiles both in vitro and in vivo, yet had no significant
      effect on the already decreased parameters in chronically affected OLETF rats.
      These data suggest that there is a tendency for macrophage inflammatory products
      to increase in acute type I and to decrease in chronic type II DM; and that TQ
      has the potential to normalise the elevated levels of these macrophage-derived
      inflammatory mediators.

PMID- 15868111
TI  - Lack of suppression of plasma glucagon levels in late pregnancy persists
      postpartum only in women with previous gestational diabetes mellitus.
AB  - The aim of the present study was to examine fasting (0') and postglucose glucagon
      levels in normal and gestational diabetes mellitus (GDM) pregnancy, as available
      data are somewhat conflicting. To this end we studied 18 women with GDM at 26-32
      weeks of pregnancy and compared these with 26 normal pregnant women matched for
      age and BMI. We also examined glucagon suppressibility postpartum (2-4 months) in
      the same ex-GDM women, in whom normal glucose tolerance was confirmed (WHO
      criteria) and compared these with 17 controls matched for age and BMI. Glucose,
      insulin and glucagon levels were measured during a 100 or 75 g oral glucose
      tolerance test (OGTT) respectively. In pregnant women, baseline and 3 h after
      glucose ingestion, plasma glucagon levels were significantly higher (p < 0.05) in
      women with GDM compared to normal women. Interestingly, in normal pregnancy a
      significant increase (p < 0.01) of postglucose plasma glucagon levels at 1 and 2
      h compared to baseline levels was observed, while there was no change in GDM
      pregnancy. In postpartum euglycaemic women, there was no difference in basal
      glucagon levels between the two groups. A differential glucagon response during
      OGTT was observed: in control women there was a significant glucagon suppression
      (p < 0.01) at 2 h, while there was a significant glucagon increase (p < 0.01) 1 h
      after glucose ingestion, in ex-GDM women. We conclude that (a) absence of the
      suppressibility of glucagon in ex-GDM women with normal OGTT may indicate insulin
      resistance and might be involved in the natural history towards glucose
      intolerance; and (b) nonsuppression of glucagon in normal late pregnancy as well
      as in pregnancy complicated by GDM may be due to "physiological" insulin
      resistance of the alpha cells during this period.

PMID- 15868112
TI  - Gender, body mass index and socio-demographic variables associated with knowledge
      about type 2 diabetes mellitus among 13,293 Mexican students.
AB  - The main aim of this study was to evaluate correlates of the knowledge Mexican
      young people have about type 2 diabetes mellitus (DM) risk and prevention. We
      developed a cross-sectional study in public schools in Morelos, in central Mexico
      during 1998-1999 in 13,293 students (11-24 years). We determined body mass index
      (BMI) with anthropometric measurements (height and weight). Using questionnaire
      data, we constructed a DM knowledge-based scale. Statistical analysis was done
      using an ordinal, logistic regression model. Only 1.6% of the students (95%CI =
      1.4-1.8) had high DM knowledge levels; 85.6% (95%CI = 84.9-86.1) had low levels.
      The factors with the strongest associations with high levels of knowledge about
      type 2 DM among the Mexican students in this study were: being in high school or
      at university (vs. junior high), urban residence, higher socio-economic level,
      and BMI indicating overweight or obesity. Other socio-demographic factors
      correlated with high levels of knowledge about the disease, but with slightly
      weaker associations, included female gender, higher age, higher academic
      achievement (grades) and higher education level of the student's mother. While
      young men who were overweight or obese were 2.6 and 3.4 times more likely to have
      high levels of knowledge about DM (95%CI = 1.9-3.6 and 2.1-5.5, respectively),
      young women who were overweight or obese were only 1.4 and 1.1 times more likely
      to have high knowledge about DM (95%CI = 1.0-1.9 and 0.6-1.8, respectively).
      Mexican young people have limited knowledge about DM, although this chronic
      disease is increasingly common in Mexico as in many other countries.

PMID- 15868113
TI  - Abstracts from the 24th Workshop of the Study Group on Artificial Insulin
      Delivery, Pancreas and Islet Transplantation (AIDPIT) of the European Association
      for the Study of Diabetes (EASD). Igls, Austria. January 23-25, 2005.

PMID- 15868114
TI  - Introduction.

PMID- 15868115
TI  - The association of hypertension and diabetes: prevalence, cardiovascular risk and
      protection by blood pressure reduction.
AB  - Diabetes and hypertension frequently coexist, and their combination provides
      additive increases in the risk of life-threatening cardiovascular events. Recent
      guidelines agree on the need for early, aggressive reduction of blood pressure,
      with a goal of <130/80 mmHg, in patients with diabetes. The mechanism that
      underpins the increased sensitivity of diabetic subjects to hypertension is not
      known, but may involve impaired autoregulation or attenuated nocturnal decrease
      of blood pressure. All classes of antihypertensive agents are effective in
      reducing blood pressure in diabetic subjects, and all show evidence of a
      concomitant reduction in cardiovascular risk. Although there is some evidence
      that agents that interrupt the renin-angiotensin system (RAS) provide greater
      protective effects, the data are not conclusive. However, most diabetic subjects
      will require combination therapy to reach goal blood pressure. Antihypertensive
      drugs can also significantly influence the probability that otherwise healthy
      individuals will develop metabolic syndrome or type 2 diabetes. While diuretics
      and betablockers have a prodiabetic effect, angiotensin-converting enzyme
      inhibitors and angiotensin II receptor blockers may prevent diabetes more
      effectively than the metabolically neutral calcium channel blockers. Given that
      diabetes is an important cardiovascular risk factor, there is the potential for
      reductions in risk due to reduced blood pressure to be offset by an increased
      risk due to the development of diabetes. Such concerns should be considered in
      the selection of antihypertensive therapy.

PMID- 15868116
TI  - Vascular protection in diabetes: a pharmacological view of angiotensin II type 1
      receptor blockers.
AB  - Vascular protection is key to reducing the morbidity associated with diabetes.
      Angiotensin II is known to exert a variety of deleterious effects on the
      vasculature, and this is likely to be a major explanation of the protective
      benefits observed with blockade of the renin-angiotensin-aldosterone system
      (RAAS). Intriguingly, RAAS blockade also appears to reduce the onset of new
      diabetes, which points to a fundamental effect on metabolism. Recent developments
      have thrown new light onto the mechanism of these effects. The importance of
      unopposed stimulation of the angiotensin II type 2 (AT(2)) receptor in vascular
      protection is recognised, and recent studies have revealed that some angiotensin
      II type 1 (AT(1)) receptor blockers (ARBs) show partial peroxisome proliferator
      activated receptor-gamma (PPARgamma) agonistic activity in vitro, an effect that
      is at least partly due to direct interaction with PPARgamma itself. There is a
      clear order of potency among the ARBs, with telmisartan the most potent and the
      only ARB to show an effect at physiologically achievable plasma concentrations.
      Adiponectin, an adipokine closely involved with glucose sensitisation, is also
      modulated by the relative activation of AT(1) and AT(2) receptors. Such effects
      would suggest that important benefits may result from the use of ARBs in clinical
      practice, although confirmation of the clinical relevance will depend upon the
      results of numerous ongoing studies.

PMID- 15868117
TI  - Obesity, hypertension and insulin resistance.
AB  - Being overweight or obese has become highly prevalent in Western countries and
      are rapidly reaching epidemic proportions in the developing world. Obesity
      related disorders, such as hypertension and diabetes, are also increasing at an
      alarming rate. The relationship between obesity, hypertension and insulin
      resistance is well recognised, but the molecular mechanisms involved remain
      relatively poorly understood. Adipose tissue plays a key role in the pathogenesis
      of the metabolic syndrome. It serves as an important source of pro-inflammatory
      molecules, including leptin, tumour necrosis factor alpha, angiotensin II and
      interleukin-6, as well as anti-inflammatory molecules, such as adiponectin.
      Knowledge of how these adipose tissue-derived factors influence metabolic and
      cardiovascular disease has recently expanded. Leptin is now considered to play a
      key role in the elevation of sympathetic activity commonly found in obese,
      hypertensive patients, and decreased secretion of adiponectin appears to be an
      important predictor of diabetes. The ectopic storage of excess fat in skeletal
      muscle, liver or pancreas, due to the decreased capacity of adipose tissue to
      scavenge excess calories, may also play a role in the development of insulin
      resistance and type 2 diabetes. Overall, continuing research into the
      relationship between adipose-tissue biology and metabolic abnormalities may lead
      to a better understanding of the molecular mechanisms underlying the relationship
      between obesity and cardiovascular disease, and ultimately provide alternative
      treatments for the control of potentially life-threatening conditions.

PMID- 15868118
TI  - Renin-angiotensin-aldosterone system blockade and renal protection: angiotensin
      converting enzyme inhibitors or angiotensin II receptor blockers?
AB  - Renal function is closely associated with cardiovascular risk, to the extent that
      even minor renal abnormalities, which are present in 10% of the general
      population, carry a greatly elevated risk of cardiovascular disease, target-organ
      damage and death. Reducing blood pressure by 20 mmHg or more in patients with
      severe hypertension (>160/100 mmHg) and advanced renal disease is sufficient to
      ensure a considerable reduction in proteinuria. In patients with less severe
      disease, however, blockade of the renin-angiotensin-aldosterone system (RAAS) is
      necessary to restore normal renal function. Clinical studies have shown that
      angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor
      blockers (ARBs), which both overcome the activity of angiotensin II, provide
      renoprotection in diabetics and non-diabetic populations. Which class of drugs is
      more effective remains a subject of debate, but the evidence favours ARBs for
      providing more effective renoprotection in patients at risk of diabetic
      nephropathy. The ARBs preserve renal haemodynamics and reduce progression to end
      stage renal disease by around 25% in patients with overt nephropathy and prevent
      progression to overt disease by up to 70% in patients with mild renal impairment.
      The combination of ARBs and ACE inhibitors is even more protective, halving the
      number of patients with progression of renal impairment compared with either
      monotherapy. Long-term clinical studies now under way will help to establish the
      relative efficacies of the ARBs and ACE inhibitors and provide greater insight
      into the benefits of combination therapy.

PMID- 15868119
TI  - Preventing renal complications in diabetic patients: the Diabetics Exposed to
      Telmisartan And enalaprIL (DETAIL) study.
AB  - Diabetic nephropathy is characterised by hypertension and persistent proteinuria.
      If ineffectively controlled, a progressive decline in renal function can result
      in end-stage renal disease. Patients with diabetic nephropathy are also at
      greatly increased risk of cardiovascular disease. Angiotensin-converting enzyme
      (ACE) inhibitors display additional renoprotective effects beyond systemic blood
      pressure lowering, perhaps due to reduction in intraglomerular pressure by
      inhibition of angiotensin II activity. In type 2 diabetics, ACE inhibitors have
      variable effects, with some studies showing a reduction in microalbuminuria,
      prevention of the progression to macroalbuminuria and maintenance of renal
      function. Randomised studies have demonstrated that angiotensin II receptor
      blockers (ARBs), as well as controlling systemic blood pressure, delay
      progression of proteinuria in patients with diabetic nephropathy. Telmisartan has
      a number of features that may make it particularly suitable for the treatment of
      diabetic nephropathy. In addition to its long duration of action and almost
      exclusive faecal excretion, its high lipophilicity should assist in tissue
      penetration. The Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) study
      was designed to compare the long-term renal outcome of treatment with telmisartan
      40.80 mg versus enalapril 10.20 mg (with titration to the higher dose after 4
      weeks) in patients with type 2 diabetes, mild-to-moderate hypertension and
      albuminuria. The primary endpoint is the change in glomerular filtration rate
      after 5 years' randomised treatment. Secondary endpoints are annual changes in
      glomerular filtration rate, serum creatinine and urinary albumin excretion, as
      well as incidences of end-stage renal disease, cardiovascular events, all-cause
      mortality and adverse events. The groundbreaking DETAIL study revealed that
      telmisartan conferred comparable renoprotection to enalapril and was associated
      with a low incidence of mortality.

PMID- 15868120
TI  - The ONTARGET/TRANSCEND Trial Programme: baseline data.
AB  - Cardiovascular risk is determined by multiple risk factors, all of which greatly
      increase the chance of morbidity and mortality. So-called "normal" levels of
      these factors are not biologically normal, so current strategy is based on
      estimations of a person's global cardiovascular risk, and then using appropriate
      combinations of treatments in higher-risk people. Angiotensin-converting enzyme
      (ACE) inhibitors and angiotensin II receptor blockers (ARBs) provide multiple
      actions against many of the risk factors for cardiovascular disease and also show
      some evidence of an effect that is independent of blood pressure reduction. The
      ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial
      (ONTARGET) is designed to clarify whether an ARB (telmisartan), an ACE inhibitor
      (ramipril) or a combination of both confers blood pressure-independent
      cardioprotection in high-risk patients whose blood pressure is well controlled.
      The Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with
      cardiovascular Disease (TRANSCEND) trial has the same endpoints, but will compare
      telmisartan with placebo in patients who are intolerant to an ACE inhibitor.
      Primary endpoints for both trials are the composite of cardiovascular death, non
      fatal myocardial infarction, non-fatal stroke or hospitalisation for heart
      failure. Recruitment is now complete, with 25 620 patients randomised in ONTARGET
      and 5926 in TRANSCEND. Baseline patient characteristics are similar to those in
      the Heart Outcomes Prevention Evaluation (HOPE) study, except that the current
      trials have greater ethnic diversity (including an important cohort from Asia).
      The subjects are slightly older and mean blood pressure at randomisation is again
      normal, but slightly lower than in HOPE. The use of beta-blockers and lipid
      lowering therapy, known to reduce mortality and morbidity, is also higher in
      ONTARGET/TRANSCEND. These trials are the largest comparisons to date of ARB and
      ACE-inhibitor therapy in high-risk patients with controlled blood pressure, and
      the results will contribute significantly to the future treatment of
      cardiovascular disease.

PMID- 15868121
TI  - Treating the metabolic syndrome: telmisartan as a peroxisome proliferator
      activated receptor-gamma activator.
AB  - Hypertension commonly occurs as part of a genetically complex disorder of
      carbohydrate and lipid metabolism known as the metabolic syndrome. Most current
      antihypertensive drugs appear ineffective against the metabolic syndrome, which
      is a strong predictor of cardiovascular disease and death in affected patients.
      Angiotensin II can influence the activity of certain genes and cellular and
      biochemical pathways that may contribute to the pathogenesis of the metabolic
      syndrome. However, as a class, angiotensin II receptor blockers (ARBs) have
      proven only minimally to modestly effective in ameliorating the disturbances in
      carbohydrate and lipid metabolism that characterise the metabolic syndrome.
      Recent preclinical studies indicate that the ARB telmisartan acts as a selective
      peroxisome proliferators-activated receptor-gamma (PPARgamma) modulator when
      tested at concentrations that might be achievable with oral doses recommended for
      treatment of hypertension; this property does not appear to be shared by other
      ARBs. PPARgamma is a nuclear receptor that influences the expression of multiple
      genes involved in carbohydrate and lipid metabolism and is an attractive
      therapeutic target for the prevention and control of insulin resistance, type 2
      diabetes and atherosclerosis. In cellular transactivation assays, telmisartan
      functioned as a partial agonist of PPARgamma and achieved 25-30% of maximal
      receptor activation attained with conventional PPARgamma ligands. Preclinical and
      clinical studies indicate that administration of telmisartan can improve
      carbohydrate and lipid metabolism without causing the side effects that accompany
      full PPARgamma activators. If the preliminary data are supported by the results
      of ongoing large-scale clinical studies, telmisartan could have a central role in
      the prevention and treatment of metabolic syndrome, diabetes and atherosclerosis.

PMID- 15868122
TI  - Detection of residual tumor after radiofrequency ablation of liver metastasis
      with dual-modality PET/CT: initial results.
AB  - The aim of this study was to determine the accuracy of dual-modality positron
      emission tomography(PET)/computed tomography (CT) in the detection of residual
      tumor after radiofrequency ablation (RFA) of liver metastasis of colorectal
      cancer. Eleven patients with 16 hepatic metastases (mean size 2.9 cm) from
      colorectal cancer were enrolled in this study, and 19 RFA procedures and 32
      PET/CT examinations were performed. The patients had PET/CT before and after RFA
      using [18F]-2-fluoro-2-deoxy-D: -glucose. CT images alone were read by two
      radiologists, PET images alone were evaluated by two nuclear physicians. Fused
      images were read by one physician of each speciality in consensus. The accuracy
      for detection of residual tumor by the different imaging modalities following RFA
      was assessed. Eleven patients with a mean age of 63 (range 55-71) years were
      evaluated. The mean follow-up period was 393 days. The overall procedure-based
      sensitivity for detection of residual tumor was 65% for PET and PET/CT and 44%
      for CT alone. The accuracies were 68% and 47%, respectively. Four patients had
      residual tumor after RFA, six patients total developed local recurrence. PET/CT
      therefore possibly proved superior to CT alone when assessing the liver for
      residual tumor after RFA.

PMID- 15868123
TI  - Giant-cell tumours of bone of the hand and wrist: a review of imaging findings
      and differential diagnoses.
AB  - Giant-cell tumour of bone (GCTOB) is a benign, locally aggressive, primary bone
      tumour. Involvement of the distal radius accounts for between 10 and 12% of cases
      of GCTOB, with the bones of the hand and wrist being rarely affected. GCTOB most
      commonly affects skeletally mature patients between the ages of 20 and 40 years,
      with the peak incidence being in the third decade. Women are affected slightly
      more commonly than men. GCTOB involving the bones of the hand most commonly
      occurs in a central location, which differs from the usual eccentric location
      seen in GCTOB at other sites. The radiographic features of GCTOB in the hand and
      wrist are presented. The role of bone scintigraphy, computed tomography and
      magnetic resonance imaging is discussed. Evaluation of the postoperative patient
      is also addressed, including the role of dynamic contrast-enhanced magnetic
      resonance imaging. A comprehensive review of the potential differential diagnoses
      that should be considered when GCTOB is suspected in the hand and wrist is also
      presented.

PMID- 15868124
TI  - Distribution of mesorectal lymph nodes in rectal cancer: in vivo MR imaging
      compared with histopathological examination. Initial observations.
AB  - The aim of this work was to determine the distribution of mesorectal lymph nodes
      using T2-weighted magnetic resonance (MR) imaging compared with histopathological
      findings in patients with rectal carcinoma. Sixteen patients with rectal
      carcinoma undergoing primary surgery without pre-operative neoadjuvant treatment
      were evaluated using 3-mm axial T2-weighted MR imaging. The position of each
      visible mesorectal node on imaging was localised by measuring its minimum
      distance from the mesorectal fascia (d(m)), its minimum distance from the rectal
      wall (d(r)) and its distance from the distal tumour margin (d(v)). Independent
      assessment of d(m), d(r) and d(v) was made at histopathological examination.
      Eighty-five mesorectal nodes on in vivo MR imaging were matched to
      histopathological findings. On imaging, 67/85 mesorectal nodes were found at the
      level of the tumour and 84/85 were identified at or within 5 cm proximal to the
      tumour. Only one out of 85 nodes was seen below the inferior tumour margin. The
      mean difference of d(m) and d(r) obtained on in vivo MR imaging and
      histopathological examination was 0.7 mm (95% confidence interval, CI, -0.12 to
      1.42 mm) and -1.1 mm (95% CI -2.29 to 0.14 mm), respectively. Almost all
      mesorectal nodes visible on MR imaging were found at the level of tumour or
      within 5 cm proximal to the tumour. This has implications for the planning of MR
      imaging and the level of mesorectal transection at surgery.

PMID- 15868125
TI  - Detection of liver metastases under 2 cm: comparison of different acquisition
      protocols in four row multidetector-CT (MDCT).
AB  - This study compared different acquisition protocols performance to detect small
      liver metastases (<2 cm). Thirty consecutive patients with histologically proven
      hepatic metastases were explored by MDCT at the liver equilibrium phase by four
      successive acquisitions. We compared the following protocols (1-4): 5/30/1.5
      (section thickness/table speed/pitch); 5/15/0.75; 5/11.25/0.75; and 2.5/15/1.5
      with the same X-ray dose. The gold standard was based on patient radiological
      follow-up. Evolutive lesions were considered as true positive (TP). The described
      lesions, not found on the follow-up exams despite tumoral progression, were
      considered as false positive (FP). Stable lesions could not be considered as
      metastasis and were eliminated. One hundred and seventy-six lesions were
      detected: 61 TP and 91 FP. Twenty-four lesions were eliminated. The mean kappa
      values for protocols 1, 2, 3 and 4 were, respectively, 0.43, 0.68, 0.73 and 0.51
      (0.61-0.80: substantial agreement) and the mean areas under the ROC curve were,
      respectively, 0.76, 0.87, 0.86 and 0.80. The results of protocols 2 and 3 were
      significantly superior to those of protocols 1 and 4. MDCT protocols using thin
      sections or an increased table speed are less efficient in detecting small
      metastases.

PMID- 15868126
TI  - Detecting chaotic structures in noisy pulse trains based on interspike interval
      reconstruction.
AB  - The nonlinear prediction method based on the interspike interval (ISI)
      reconstruction is applied to the ISI sequence of noisy pulse trains and the
      detection of the deterministic structure is performed. It is found that this
      method cannot discriminate between the noisy periodic pulse train and the noisy
      chaotic one when noise-induced pulses exist. When the noise-induced pulses are
      eliminated by the grouping of ISI sequence with the genetic algorithm, the
      chaotic structure of the chaotic firings becomes clear, and the noisy chaotic
      pulse train could be discriminated from the periodic one.

PMID- 15868127
TI  - Information coding by ensembles of resonant neurons.
AB  - In the present paper, we propose a novel neural procedure for signal processing
      and coding based on the subthreshold oscillations and resonance of the neural
      membrane potential that could be used by real neurons to perform frequency
      spectra analysis and information coding of incoming signals. Taking into account
      the biophysical properties of the neural membranes, we note that the subthreshold
      resonant behaviour they exhibit can be used to analyse incoming signals and
      represent them in the frequency domain. We study the reliability of the
      representation of signals depending on the biophysical parameters of the neurons,
      the fault-tolerance of this coding scheme and its robustness against noise and in
      the presence of spikes. The principal characteristics of our system are the use
      of the physical phenomenon of neural resonance (rarely considered in the
      literature for signal coding); it fits well with the biophysical parameters of
      most neurons that exhibit subthreshold oscillations; it is compatible with
      experimental data; and it can be easily integrated in a more general model of
      information processing and coding that includes communication between neurons
      based on spikes.

PMID- 15868128
TI  - [Magnetic drug targeting. New paths for the local concentration of drugs for head
      and neck cancer].

PMID- 15868129
TI  - [Sensorineural hearing loss in LEOPARD syndrome].
AB  - The rare multiple lentigines (LEOPARD) syndrome represents a complex of skin,
      cardiac, skeletal, inner ear and other malformations. There is marked variability
      in expression of the syndrome. We report on a 20 year old man, showing typical
      lentiginosis, a retardation of growth, tachycardiac conduction abnormality,
      ophthalmologic manifestations and a sensorineural hearing loss. Pathogenesis,
      clinical and differential diagnostic aspects are discussed in this case report.
      The early diagnosis of a senosorineural hearing loss is useful in order to
      provide appropriate rehabilitation. When lentiginosis is diagnosed, it is
      important to consider further abnormalities such as cardiomyopathy, which can be
      associated with a high mortality.

PMID- 15868130
TI  - [Susac's syndrome. A rare microangiopathy of cochlea, retina, and brain].
AB  - Susac's syndrome is a rare disease characterized by encephalopathy, retinal
      artery occlusion, and a sensorineural hearing loss. Diagnosis may be difficult
      since most specialists are not familiar with this angiopathy. However, the
      typical symptom complex can mimic different pathologies, therefore requiring the
      attention of radiologists, ENT specialists, and ophthalmologists. We present a
      rare case of Susac's syndrome unveiled by audiometry results, MR imaging of the
      brain, and the ophthalmological findings..

PMID- 15868131
TI  - [Does the subjective assessment of roughness correlate with a computer-aided
      measurement of irregularity index?].
AB  - For routine clinical purposes dysphonic voices are assessed using the GRBAS scale
      or analogues. An objective measurement often includes jitter measurements. Here
      we raised the question of whether roughness estimates correlate with a computer
      aided measurement of the vocal fold cycle irregularity in 78 patients who read a
      standard text ("Nordwind und Sonne"). The samples were evaluated by 19 speech and
      voice therapy students according to the degree of roughness. The irregularity
      index was calculated according to the procedures suggested by Fourcin. Data were
      subjected to correlation analysis. A significant correlation was found between
      the irregularity index and the subjective roughness scaling. These data indicate
      that objective measurements of vibratory cycle irregularity during text reading
      can be used for clinical purposes in addition to subjective roughness scaling.

PMID- 15868132
TI  - [Hard, expanding preauricular swelling in a 6-year-old child].

PMID- 15868133
TI  - [ Intramedullary nailing (ESIN) in clavicular pseudoarthroses. Results of a
      prospective clinical trial].
AB  - This prospective clinical trial was performed to assess healing, clinical outcome
      and complications after intramedullary nailing of midshaft clavicular nonunions.
      Over 2.5 years, 14 patients were included. Exclusion criteria were pathological
      fractures, bony defects, previous operative therapy, atrophic and infection
      pseudarthrosis and the patient's age: <18 years or >70 years. Results were
      evaluated after 3, 6, 12 and 18 months. Beginning 3 months after the operation,
      pain (VAS), subjective satisfaction, Constant score and DASH score were
      significantly better than preoperatively during the follow-up period (p<0.001).
      There were no infections, no implant displacements or refractures.Intramedullary
      fixation of midshaft clavicular nonunions with an elastic titanium nail is a
      safe, minimally invasive surgical technique, producing excellent functional and
      cosmetic results without additional bone grafting.

PMID- 15868134
TI  - Genome-wide linkage scans for prediabetes phenotypes in response to 20 weeks of
      endurance exercise training in non-diabetic whites and blacks: the HERITAGE
      Family Study.
AB  - AIMS/HYPOTHESIS: Impaired insulin secretion, insulin action, insulin-independent
      glucose effectiveness, glucose tolerance and the associated abnormalities in
      insulin and glucose metabolism phenotypes are precursors of type 2 diabetes.
      Genome-wide multipoint variance component linkage scans were carried out using
      654 markers to identify quantitative trait loci for insulin sensitivity, acute
      insulin response to glucose, disposition index and glucose effectiveness training
      responses in whites and blacks in the HERITAGE Family Study. METHODS: These
      phenotypes were obtained from an IVGTT with the minimal model. The distributions
      of insulin sensitivity, acute insulin response to glucose and disposition index
      training responses (post-training minus baseline) were approximately normalised
      using a square-root transformation. All phenotypes were adjusted for the effects
      of age, BMI and their respective baseline values within sex and generation by
      race prior to linkage scans. RESULTS: In blacks, a promising linkage with a
      maximum lod score of 3.1 on 19q (54-62 Mb) for glucose effectiveness training
      response was found. Six interesting linkages with lod scores of at least 1.0 were
      found for disposition index training response in whites. They included 1p (30
      Mb), 3q (152 Mb), 6p (23-42 Mb), 7q (95-96 Mb), 10p (15 Mb) and 12q (119-126 Mb).
      CONCLUSIONS/INTERPRETATION: Quantitative trait loci for 20 weeks of endurance
      exercise training responses in insulin action and glucose metabolism phenotypes
      were found on chromosome 19q as well as 6p and 7q, with nominal (6p, 7q) but
      consistent (6p) linkages across the races.

PMID- 15868135
TI  - Hyperinsulinaemia triggered by dietary conjugated linoleic acid is associated
      with a decrease in leptin and adiponectin plasma levels and pancreatic beta cell
      hyperplasia in the mouse.
AB  - AIMS/HYPOTHESIS: Dietary supplementation with conjugated linoleic acids (CLA) has
      a fat-reducing effect in various species, but induces severe hyperinsulinaemia
      and hepatic steatosis in the mouse. This study aimed to determine the causes of
      the deleterious effects of CLA on insulin homeostasis. METHODS: The chronology of
      adipose and liver weight, hepatic triglyceride accumulation and selected blood
      parameters, including lipids, insulin, leptin and adiponectin, was determined in
      C57BL/6J female mice fed a 1% isomeric mixture of CLA for various periods of time
      ranging from 2 to 28 days. Insulin secretion was measured in 1-h static
      incubations of pancreatic islets, and pancreas morphometric parameters were
      determined in mice fed CLA for 28 days. RESULTS: Plasma levels of leptin and
      adiponectin sharply decreased after 2 days of CLA feeding, although adipose
      tissue mass only decreased after day 6. Hyperinsulinaemia developed at day 6 and
      consistently worsened up to day 28, in parallel with increases in hepatic lipid
      content. Islets from CLA-fed mice displayed three- to four-fold increased rates
      of glucose-stimulated insulin secretion, both in the absence and presence of
      isobutyl methylxanthine or carbachol. The increased insulin-releasing capacity of
      islets from CLA-fed mice was explained by an increase in beta cell mass and
      number. CONCLUSIONS/INTERPRETATION: The data suggest that CLA supplementation
      induces a profound reduction of leptinaemia and adiponectinaemia, followed by
      hyperinsulinaemia due to the increased secretory capacity of pancreatic islets,
      leading, in turn, to liver steatosis. These observations cast doubt on the safety
      of dietary supplements containing CLA.

PMID- 15868136
TI  - Abnormal viscoelastic behaviour of passive ankle joint movement in diabetic
      patients: an early or a late complication?
AB  - AIMS/HYPOTHESIS: The goal of the present study was to compare the range of motion
      and both the viscous and elastic components of passive ankle joint movement in
      short- and long-term diabetic patients with that of a control population.
      METHODS: Thirty-four diabetic patients and 16 control subjects entered into the
      study. Patients with a history of over 15 years of diabetes were considered as a
      long-term diabetic group. In order to quantify the passive ankle joint movement,
      a device was designed to measure the dorsi- and plantar-flexion angle and the net
      moment at the ankle. Elastic behaviour was examined as the separate slope of
      regression lines (stiffness) of plantar and dorsal components in the loading
      moment-angle curve. It was also examined as the slope of the regression line in
      the final 10% of each component. Hysteresis, a characteristic of viscoelastic
      materials that indicates loss of energy during unloading, was corrected for range
      of motion and used to examine viscous behaviour of the ankle joint. RESULTS:
      Total and plantar ranges of motion were significantly lower in long-term diabetic
      patients than in short-term diabetic and control groups (p < 0.05). Plantar
      flexion stiffness was significantly lower in short-term diabetic patients than in
      control subjects and long-term diabetic groups (p < 0.05). Corrected hysteresis
      was significantly higher in long-term diabetic than in short-term diabetic and
      control (p < 0.05) groups in the dorsal range of motion.
      CONCLUSIONS/INTERPRETATION: This study shows that both decreased plantar and
      total ankle joint ranges of motion, and increased viscous component of passive
      ankle joint movement are among the late complications of diabetes.

PMID- 15868137
TI  - Enhanced soluble CD40 ligand contributes to endothelial cell dysfunction in vitro
      and monocyte activation in patients with diabetes mellitus: effect of improved
      metabolic control.
AB  - AIMS/HYPOTHESIS: Inflammation plays a pathogenic role in the development of
      accelerated atherosclerosis in diabetes. Soluble CD40 ligand (sCD40L) is enhanced
      in diabetes; however, the molecular mechanisms linking sCD40L to accelerated
      atherosclerosis in diabetes are still unclear. We tested the hypothesis that
      sCD40L may be involved in the vascular complications in diabetes and exerts its
      effect by triggering inflammatory reactions on mononuclear and endothelial cells
      (ECs). METHODS: We studied 70 patients, 40 with type 2 and 30 with type 1
      diabetes, with a history or physical examination negative for cardiovascular
      disease, and 40 non-diabetic and 30 healthy subjects, matched with the type 2 and
      type 1 diabetic patients, respectively. Plasma and serum sCD40L, and plasma
      soluble intercellular adhesion molecule-1, soluble vascular cell adhesion
      molecule-1, E-selectin and monocyte chemo-attractant protein-1 (MCP-1) were
      measured. Adhesion molecules and MCP-1 release, the ability to repair an injury
      in ECs, and O2- generation in monocytes were analysed in vitro after stimulation
      with serum from patients or controls. RESULTS: Type 2 and type 1 diabetic
      patients had significantly higher sCD40L levels than controls. Furthermore, high
      sCD40L was associated with in vitro adhesion molecules and MCP-1 release,
      impaired migration in ECs and enhanced O2- generation in monocytes. Improved
      metabolic control was associated with a reduction of plasma sCD40L by 37.5% in 12
      type 1 diabetic patients. Furthermore, elevated sCD40L in diabetic patients was
      significantly correlated with HbA1c levels. CONCLUSIONS/INTERPRETATION:
      Upregulation of sCD40L as a consequence of persistent hyperglycaemia in diabetic
      patients results in EC activation and monocyte recruitment to the arterial wall,
      possibly contributing to accelerated atherosclerosis development in diabetes.

PMID- 15868138
TI  - Hub qualitative blood culture is useful for diagnosis of catheter-related
      infections in critically ill patients.
AB  - OBJECTIVE: To assess clinical safety and accuracy of qualitative blood culture
      drawn through the hub for ruling out catheter-related infection (CRI). DESIGN AND
      SETTING: Prospective observational study in a surgical intensive care unit.
      PATIENTS: All patients with sepsis of unknown origin and possibly due to a CRI.
      INTERVENTIONS: Blood culture drawn through a central venous catheter (CVC) just
      before the catheter was cultured. MEASUREMENTS AND RESULTS: In 126 patients we
      investigated 135 cases of sepsis of unknown origin. Using a clinical and
      bacteriological approach as the reference, the performance of the CVC blood
      culture was evaluated by the calculation of sensitivity, specificity, and
      positive and negative predictive values. When CVC blood culture was positive, the
      time to positivity was considered. Using standard definitions, seven CRIs were
      diagnosed. CVC blood culture identified five CRIs including the three episodes of
      catheter-related bacteremia. The method missed two coagulase-negative
      staphylococcus CRIs without bacteremia. Thirteen false-positive results occurred,
      including seven bacteremias from a distant source. The CVC blood culture had a
      sensitivity of 71% (CI 30-95%), specificity of 90% (CI 83-94%), negative
      predictive value of 98% (CI 93-100%), and positive predictive value of 28% (CI 11
      54%). In cases of catheter-related bacteremia the time to positivity of CVC blood
      culture was 24 h or less. CONCLUSIONS: Negative CVC blood culture at 24 h seems
      useful for management of CVC in selected critically ill surgical patients
      developing a clinical sepsis. The subsequent risk of catheter-related bacteremia
      cannot be excluded advocating for an uninterrupted clinical and bacteriological
      survey.

PMID- 15868139
TI  - The cyclopentenone prostaglandin 15-deoxydelta(12,14)-prostaglandin J2 attenuates
      the development of zymosan-induced shock.
AB  - OBJECTIVE: Multiple-organ failure (MOF) is defined as the progressive
      deterioration in function which occurs in several organs or systems in patients
      with septic shock, multiple trauma, severe burns, or pancreatitis. This study
      investigated the effect of 15-deoxy-delta(12,14)-PGJ2 (15d-PGJ2), a PPAR-gamma
      ligand, in a model of zymosan-induced nonseptic shock in mice. MATERIALS AND
      METHODS: Mice were randomly assigned to one of four groups (n=10 each) and
      treated i.p. as follows: group 1, zymosan (500 mg/kg suspended in saline
      solution) and vehicle (10% DMSO); group 2, zymosan (500 mg/kg suspended in saline
      solution) plus 15d-PGJ2 (30 microg/kg, suspended in 10% DMSO) 1 h before and 6 h
      after zymosan administration; group 3, 15d-PGJ2 (30 microg/kg, suspended in 10%
      DMSO; group 4, vehicle for PGJ2 (10% DMSO) always 1 h before and 6 h after saline
      administration. After 18 h mice were killed and tissues and biological fluids
      used for biochemical, immunohistochemical, and histological analysis.
      MEASUREMENTS AND RESULTS: 15d-PGJ2 inhibited the inflammatory response and
      significantly reduced peritoneal mononuclear cell infiltration and histological
      injury in mice. A significant protection was demonstrated in kidney, liver, and
      pancreas injury by the reduction in amylase, lipase, creatinine, AST, ALT,
      bilirubin, and alkaline phosphatase levels. 15d-PGJ2 also reduced the appearance
      of nitrotyrosine in the inflamed intestinal tissues. Histological examination
      revealed a significant reduction in zymosan-induced intestinal damage in 15d-PGJ2
      treated mice. CONCLUSIONS: Our findings demonstrate that 15d-PGJ2 exerts potent
      anti-inflammatory effects on zymosan-induced shock.

PMID- 15868141
TI  - Automated generation and evaluation of specific MHC binding predictive tools: ARB
      matrix applications.
AB  - Prediction of which peptides can bind major histocompatibility complex (MHC)
      molecules is commonly used to assist in the identification of T cell epitopes.
      However, because of the large numbers of different MHC molecules of interest,
      each associated with different predictive tools, tool generation and evaluation
      can be a very resource intensive task. A methodology commonly used to predict MHC
      binding affinity is the matrix or linear coefficients method. Herein, we
      described Average Relative Binding (ARB) matrix methods that directly predict
      IC(50) values allowing combination of searches involving different peptide sizes
      and alleles into a single global prediction. A computer program was developed to
      automate the generation and evaluation of ARB predictive tools. Using an in-house
      MHC binding database, we generated a total of 85 and 13 MHC class I and class II
      matrices, respectively. Results from the automated evaluation of tool efficiency
      are presented. We anticipate that this automation framework will be generally
      applicable to the generation and evaluation of large numbers of MHC predictive
      methods and tools, and will be of value to centralize and rationalize the process
      of evaluation of MHC predictions. MHC binding predictions based on ARB matrices
      were made available at http://epitope.liai.org:8080/matrix web server.

PMID- 15868142
TI  - Genomic organization of the channel catfish CD45 functional gene and CD45
      pseudogenes.
AB  - CD45 is a transmembrane protein tyrosine phosphatase, which in mammals plays an
      important role in T and B cell receptor and cytokine signaling. Recently, a
      catfish cDNA was shown to contain all characteristic CD45 features: an
      alternatively spliced amino-terminus, a cysteine-rich region, three fibronectin
      domains, a transmembrane region, and two phosphotyrosine phosphatase domains.
      However, analyses of CD45 cDNAs from various catfish lymphoid cell lines
      demonstrated that catfish CD45 is unique in that it contains a large number of
      alternatively spliced exons. Sequence analyses of cDNAs derived from the catfish
      clonal B cell line 3B11 indicated that this cell line expresses up to 13
      alternatively spliced exons. Furthermore, sequence similarity among the
      alternatively spliced exons suggested duplication events. To establish the exact
      number and organization of alternatively spliced exons, a bacterial artificial
      chromosome library was screened, and the catfish functional CD45 gene plus six
      CD45 pseudogenes were sequenced. The catfish functional CD45 gene spans 37 kb and
      contains 49 exons. In comparison, the human and pufferfish CD45 genes consist of
      34 and 30 exons, respectively. This difference in the otherwise structurally
      conserved catfish gene is due to the presence of 18 alternatively spliced exons
      that were likely derived through several duplication events. In addition,
      duplication events were also likely involved in generating the six pseudogenes,
      truncated at the 3' ends. A similarly 3' truncated CD45 pseudogene is also
      present in the pufferfish genome, suggesting that this specific CD45 gene
      duplication occurred before catfish and pufferfish diverged (approximately 400
      million years ago).

PMID- 15868140
TI  - Cystic fibrosis lung disease: genetic influences, microbial interactions, and
      radiological assessment.
AB  - Cystic fibrosis (CF) is a multiorgan disease caused by mutation of the CF
      transmembrane conductance regulator (CFTR) gene. Obstructive lung disease is the
      predominant cause of morbidity and mortality; thus, most efforts to improve
      outcomes are directed toward slowing or halting lung-disease progression. Current
      therapies, such as mucolytics, airway clearance techniques, bronchodilators, and
      antibiotics, aim to suppress airway inflammation and the processes that stimulate
      it, namely, retention and infection of mucus plaques at the airway surface. New
      approaches to therapy that aim to ameliorate specific CFTR mutations or
      mutational classes by restoring normal expression or function are being
      investigated. Because of its sensitivity in detecting changes associated with
      early airway obstruction and regional lung disease, high-resolution CT (HRCT)
      complements pulmonary function testing in defining disease natural history and
      measuring response to both conventional and experimental therapies. In this
      review, perspectives on the genetics and microbiology of CF provide a context for
      understanding the increasing importance of HRCT and other imaging techniques in
      assessing CF therapies.

PMID- 15868144
TI  - Transportation mechanism for vanillin uptake through fungal plasma membrane.
AB  - Protoplasts of the basidiomycete, Fomitopsis palustris (formerly Tyromyces
      palustris), were utilized to study a function of the fungal plasma membrane.
      Fungal protoplasts exhibited metabolic activities as seen with intact mycelial
      cells. Furthermore, the uptake of certain compounds into the protoplast cells was
      quantitatively observed by using non-radioactive compounds. Vanillin was
      converted to vanillyl alcohol and vanillic acid as major products and to
      protocatechuic acid and 1,2,4-trihydroxybenzene as trace products by protoplasts
      prepared from F. palustris. Extracellular culture medium showed no activity
      responsible for the redox reactions of vanillin. Only vanillic acid was detected
      in the intracellular fraction of protoplasts. However, the addition of
      disulfiram, an aldehyde dehydrogenase inhibitor, caused an intracellular
      accumulation of vanillin, strongly suggesting that vanillin is taken up by the
      cell, followed by oxidation to vanillic acid. The addition of carbonylcyanide m
      chlorophenylhydrazone, which dissipates the pH gradient across the plasma
      membrane, inhibited the uptake of either vanillin or vanillic acid into the cell.
      Thus, the fungus seems to possess transporter devices for both vanillin and
      vanillic acid for their uptake. Since vanillyl alcohol was only observed
      extracellularly, the reduction of vanillin was thought to be catalyzed by a
      membrane system.

PMID- 15868143
TI  - Characterization of the T-cell receptor gamma locus and analysis of the variable
      gene segment expression in rabbit.
AB  - The genomic organization and expression of genes of the T-cell receptor gamma
      (TRG) locus are described for mice and humans, but not for species such as
      rabbits (Oryctolagus cuniculus), in which gammadelta T cells compose a sizeable
      proportion of T cells in the periphery. We cloned 200 kb of the rabbit TRG locus
      and determined the TRGV gene usage in adult and newborn rabbits by RT-PCR. We
      identified two TRGJ genes, one TRGC gene, and 22 TRGV genes, all of which encoded
      functional variable regions. One TRGV gene is the unique member of the TRGV2
      subgroup, whereas the other genes belong to the TRGV1 subgroup. Evolutionary
      analyses of TRGV1 genes identified three distinct groups that can be explained by
      separate duplication events in the rabbit genome. Evidence of gene conversion
      between TRGV1.1 and TRGV1.6 was observed. Both TRGV1 and TRGV2 subgroup genes
      were expressed in the spleen, intestine, and appendix of adult rabbits, and the
      repertoire of TRGV genes expressed in these tissues was similar. In these tissues
      from newborns, and in skin from adults, only the genes from the TRGV1 subgroup
      were expressed. Greater TRGV-J junctional diversity was found in tissues from
      adult compared to newborn rabbits. Our analyses indicate rabbits have a larger
      germ line encoded TRG repertoire compared with that of mice and humans. In
      addition, we found TRGV gene usage is alike in most tissues of rabbits similar to
      that found in humans but in contrast to that found in mice.

PMID- 15868145
TI  - Effects and interaction of 7-hydroxy methotrexate and methotrexate in leukaemic
      cells ex vivo measured by the thymidylate synthase inhibition assay.
AB  - In high dose therapy with methotrexate (MTX) the main metabolite 7-hydroxy
      methotrexate (7-OH MTX) exceeds the plasma concentration of MTX achieving about
      tenfold higher levels. To investigate the interaction between 7-OH MTX and MTX ex
      vivo, the thymidylate synthase inhibition assay was used to quantify antifolate
      effects in patient blast samples, measuring the inhibition of the key enzyme
      thymidylate synthase (TS). In 18 leukemic samples (7 ALL, 11 AML) no dose
      dependent TS inhibition was observed for 7-OH MTX. However, a statistically
      significant increase of TS inhibition (p<0.05) was observed for a 1:1 mixture of
      MTX and 7-OH MTX as compared to the effect of MTX alone. The half-maximal
      inhibitory concentrations in the short-exposure assay were 0.857 microM for MTX
      alone versus 0.088 microM for the 1:1 mixture with 7-OH MTX, respectively (p< or
      =0.05). This interaction was not observed with an excess of 7-OH MTX. Similar
      results were obtained in long exposure experiments. We conclude that there is a
      dose-dependent interaction between 7-OHMTX and MTX, despite the lack of TS
      inhibitory effects of the metabolite alone.

PMID- 15868146
TI  - Population pharmacokinetics of trastuzumab in patients with HER2+ metastatic
      breast cancer.
AB  - PURPOSE: To characterize the population pharmacokinetics of trastuzumab in
      patients with metastatic breast cancer. METHODS: A nonlinear mixed effect model
      was based on pharmacokinetic data from phase I, II, and III studies of 476
      patients. The phase I study enrolled patients with advanced solid tumors. The
      phase II and III studies enrolled patients with HER2-positive metastatic breast
      cancer. Patients in the pivotal phase II and III studies were treated with a 4
      mg/kg loading dose of trastuzumab followed by 2 mg/kg weekly for up to 840 days.
      The model adequately predicted observed trastuzumab concentrations. Model
      stability and performance were verified using bootstrap simulations. Percentiles,
      mean, and standard deviation of observed levels were compared with their
      distributions from 100 replicates of datasets simulated under the model. RESULTS:
      A two-compartment linear pharmacokinetic model best described the data and
      accounted for the long-term accumulation observed following weekly administration
      of trastuzumab. Population estimates from the base model for clearance (CL) and
      volume of distribution of the central compartment (V1) of trastuzumab were 0.225
      L/day, and 2.95 L, respectively. Estimated terminal halflife (t1/2) based on the
      population estimate was 28.5 days. Interpatient variabilities in clearance and
      volume were 43 and 29%, respectively. The number of metastatic sites, plasma
      level of extracellular domain of the HER2 receptor, and patient weight were
      significant baseline covariates for clearance, volume, or both (P<0.005).
      However, these covariate effects on trastuzumab exposure were modest and not
      clinically important in comparison with the large inter-patient variability of
      CL. Concomitant chemotherapy (anthracycline plus cyclophosphamide, or paclitaxel)
      did not appear to influence clearance. CONCLUSION: This population
      pharmacokinetic model can predict trastuzumab exposure in the long-term treatment
      of patients with metastatic breast cancer and provide comparison of alternative
      dosage regimens via simulation.

PMID- 15868147
TI  - Irinotecan combined with docetaxel in pre-treated metastatic breast cancer
      patients: a phase II study.
AB  - PURPOSE: This is a phase II study where a novel chemotherapy combination was
      tested in pre-treated breast cancer patients: docetaxel and irinotecan have
      already been established as agents for breast and colorectal cancer,
      respectively. METHODS: Forty-eight (median age 54 years, range 26-77 year)
      patients, all evaluable, were enrolled. All patients had been pre-treated with
      anthracycline-combined chemotherapy, 30 of whom were also treated with paclitaxel
      and 2 with docetaxel. World Health Organization (WHO) performance status was 0-2.
      The dominant metastasis was in the liver (54.17%), in the lungs (27.08%), in soft
      tissues (12.50%) and in the skeleton (6.25%). Treatment involved irinotecan
      infusion 200 mg/m(2) for 90 min and docetaxel infusion 80 mg/m(2) for 90 min,
      repeated once every 3 weeks. RESULTS: Twenty-five (52.08%, 95% confidence
      interval [CI] 37.95-66.21) patients showed responses: 3 complete (6.25%, 95% CI 0
      13.05) and 22 (45.83%, 95% CI 31.74-59.92) partial; the most responsive
      metastases were observed at the liver site (53.85%). Grade 3 and 4 neutropenia
      was observed in 18 patients (37.50%); 14 (29.17%) patients developed anaemia and
      three (6.25%), thrombocytopenia. Concerning non-haematologic toxicity, alopecia
      and fatigue were common; grade 3 diarrhea was observed in only one (2.08%)
      patient. CONCLUSION: The irinotecan-docetaxel combination produces quite a high
      response rate in pre-treated advanced breast cancer patients.

PMID- 15868148
TI  - Preclinical pharmacology of epothilone D, a novel tubulin-stabilizing antitumor
      agent.
AB  - PURPOSE: To determine, for various species, the pharmacological and biochemical
      properties of epothilone D (EpoD) that are relevant in establishing an
      appropriate animal model for further evaluation of this promising antitumor
      agent. METHODS: A method involving high-performance liquid chromatography (HPLC)
      was developed and used to assess the stability and protein binding of EpoD in
      plasma from various species, its metabolism by various S9 fractions, and its
      pharmacokinetics in mice. RESULTS: EpoD was stable in dog and human plasma. In
      plasma from other species, stability decreased in the order: hamster > mouse >
      guinea pig > rat. EpoD was highly bound to proteins in dog and human plasma. In
      an evaluation of S9 fractions from mouse, rat, guinea pig, dog, and human, mouse
      S9 was most efficient in metabolizing EpoD. Following administration to CD2F1
      mice, the initial half-lives for plasma elimination of EpoD were <5 min for an
      intravenous dose and <20 min for an intraperitoneal dose. CONCLUSIONS: The
      species differences in EpoD biostability and metabolism may have implications in
      assessing its antitumor activity and pharmacologic and toxicologic profiles in
      humans. Relative to humans, the mouse is not a good model for disposition of
      EpoD; the dog would be more appropriate.

PMID- 15868149
TI  - Heterogeneity of intron presence or absence in rDNA genes of the lichen species
      Physcia aipolia and P. stellaris.
AB  - Intron origin and evolution are of high interest, yet the rates of insertion and
      loss are unclear. To investigate their spread, we studied ribosomal (r)DNA
      introns from the closely related lichens Physcia aipolia and P. stellaris. Both
      taxa are replete with rDNA spliceosomal introns and autocatalytic group I
      introns, many of which show presence/absence polymorphism when screened with the
      PCR approach. This initially suggested that Physcia could be a model for studying
      intron retention and loss. However, during the course of a population-level
      analysis, we discovered widespread intron presence/absence heterogeneity within
      lichen thalli. To address this result, we sequenced multiple clones encoding
      nuclear rDNA and the single-copy elongation factor-1alpha (EF-1alpha) from
      individual thalli. These data showed extensive rDNA heterogeneity within
      individuals, rather than the presence of multiple fungi within a thallus. Our
      results suggest that considerable care must be taken when interpreting intron
      presence/absence in lichen rDNA, an observation that has general implications for
      the study of rDNA intron evolution.

PMID- 15868150
TI  - Agrobacterium-mediated gene transfer and enhanced green fluorescent protein
      visualization in the mycorrhizal ascomycete Tuber borchii: a first step towards
      truffle genetics.
AB  - Mycorrhizal ascomycetes are ecologically and commercially important fungi that
      have proved impervious to genetic transformation so far. We report here on the
      successful transient transformation of Tuber borchii, an ectomycorrhizal
      ascomycete that colonizes a variety of trees and produces highly prized hypogeous
      fruitbodies known as "truffles". A hypervirulent Agrobacterium tumefaciens strain
      bearing the binary plasmid pBGgHg was used for transformation. The genes for
      hygromycin resistance and the enhanced green fluorescent protein (EGFP), both
      under the control of vector-borne promoters, were employed as selection markers.
      Patches of dark and fluorescent hyphae were observed upon fluorescence
      microscopic examination of hygromycin-resistant mycelia. The presence of EGFP was
      confirmed by both confocal microscopy and PCR analysis. The lack in the
      transformed mycelia of the DNA coding for kanamicin resistance (a trait encoded
      by a vector-borne gene located outside of the T-DNA region) indicates that
      Agrobacterium-mediated gene transfer correctly occurred in T. borchii.

PMID- 15868151
TI  - Adenosine deaminase enzyme levels, their relation with disease activity, and the
      effect of colchicine on adenosine deaminase levels in patients with Behcet's
      disease.
AB  - Behcet's disease (BD) is a systemic vasculitis. Although its clinical
      characteristics are well defined, the etiology and immune pathogenesis are not
      clear yet. Neutrophilic vasculitis, which is a consequence of immunological
      events, is suggested as the underlying pathophysiological mechanism. Adenosine
      deaminase (ADA) is a non-specific marker of T-lymphocyte activation. A total of
      75 patients with BD (45 women and 30 men) and 25 age-matched and gender-matched
      healthy control volunteers (13 women and 12 men) were included in this study. BD
      patients were divided into three groups according to their clinical findings:
      inactive BD patients (group 1, n=25); active BD patients under colchicine
      treatment (group 2, n=25); and active BD patients without colchicine treatment
      (group 3, n=25). Plasma ADA (p-ADA) levels of all BD patients and the control
      group were measured and compared. The relationship between p-ADA levels and
      disease activity, erythrocyte sedimentation rate (ESR) and C-reactive protein
      (CRP) levels was evaluated and correlated. Patients with BD had significantly
      higher p-ADA levels (20.6+/-6.3 U/l) than control subjects (12.8+/-1.8 U/l;
      P<0.001). The p-ADA levels of patients with active BD were significantly (for
      each, P<0.05) higher than those of inactive BD patients or controls. On the other
      hand, the difference was not significant (P>0.05) between active patients with or
      without colchicine use. In addition, there were significantly positive
      correlations between p-ADA, ESR and CRP levels in patients with BD (for each,
      P<0.05). However, disease duration or haemoglobin levels were not relevant. ADA
      level may be a valuable and supportive indicator of disease activity and is not
      affected by colchicine therapy in BD.

PMID- 15868152
TI  - Domain-based homology modeling and mapping of the conformational epitopes of
      envelope glycoprotein of west nile virus.
AB  - Knowledge-based modeling has proved significantly accurate for generating the
      quality models for proteins whose sequence identity with the structurally known
      targets is greater than or equal to 40%. On the other hand, models obtained for
      low sequence identities are not reliable. Hence, a reliable and alternative
      strategy that uses knowledge of domains in the protein can be used to improve the
      quality of the model generated by the homology method. Here, we report a method
      for developing a 3D-model for the envelope glycoprotein (Egp) of west nile virus
      (WNV), using knowledge of structurally conserved functional domains amongst the
      target sequence (Egp of WNV) and its homologous templates belonging to the same
      protein family, flaviviridae. This strategy is found to be highly effective in
      reducing the root mean square deviation (RMSD) value at the Calpha positions of
      the target and its experimental homologues. The 3D structure of a protein is a
      prerequisite for structure-based drug design as well as for identifying the
      conformational epitopes that are essential for the designing vaccines. The
      conformational epitopes are mapped from the 3D structure of Egp of WNV modeled
      using the concept of an antigenic domain. A total of five such epitope
      regions/sites have been identified. They have been found distributed in the loop
      regions (surface) of the whole protein model composed of dimerization, central
      and immunological domains. These sites are proposed as the binding sites for HLA
      proteins/B-cell receptors. Binding is required to activate the immune response
      against WNV.

PMID- 15868153
TI  - Electrostatics of Cytochrome-c assemblies.
AB  - Electrostatic potentials along with computational mutagenesis are used to obtain
      atomic level insights into Cytochrome-c in order to design efficient
      bionanosensors. The electrostatic properties of wild type and mutant Cytochrome-c
      are examined in the context of their assembly, i.e. are examined in the absence
      and presence of neighboring molecules from the assembly. An intense increase in
      the positive potential ensues when the neighboring molecules are taken into
      account. This suggests that in the extrapolation of electric field effects upon
      the design of assemblies, considering the properties of only the central molecule
      may not be sufficient. Additionally, the influence of the uncharged residues
      becomes quite diminished when the molecule is considered in an assembly. This
      could pave the way for making mutants that might be more soluble in different
      media used in the construction of devices. [Figure: see text]. The electrostatic
      potential, calculated using the program DELPHI mapped on to the surface of
      Cytochrome-c when it is considered by itself (in the left column) and in the
      presence of the electrostatic field generated by the presence of the surrounding
      4 molecules on the right. The potentials range from -10kT in red to +10kT in
      blue. The central figure shows the regions that have been mutated to positively
      charged residues by placing a unit positive charge at the terminal atom of the
      respective side chain. The figures range from the wild type in the first row,
      followed by the Gln12, Asn70, Asp50, Glu90 and Ala83 mutants.

PMID- 15868154
TI  - A study on the influence of molecular properties in the psychoactivity of
      cannabinoid compounds.
AB  - Several molecular properties are calculated for a set of 26 cannabinoid compounds
      with the goal of connecting the psychoactivity of the compounds with an
      appropriate set of calculated properties. For this purpose we used quantum
      chemical (the AM1 semi-empirical method) and chemometric methods. The AM1 method
      was employed to calculate the set of quantum chemical molecular properties and
      the chemometric methods were employed with the aim of selecting the most relevant
      properties to be correlated with psychoactivity. The chemometric methods used
      were Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA) and
      the K-Nearest Neighbor (KNN) method. The chemometric analysis showed that an
      electronic property (energy of LUMO), a hydrophobic property (log P), a steric
      property (volume of the substituent at the C4 position) and a topological
      property (Lovasz-Pelikan index) were the most important variables for the
      separation between the psychoactive and psychoinactive compounds. In order to
      validate our PCA, HCA and KNN results, eight new cannabinoid compounds (with
      known psychoactivity) were used in a prediction study and were classified
      correctly by the methods used in this work, indicating that our PCA, HCA and KNN
      models are able to predict reliable psychoactivity of cannabinoid compounds.

PMID- 15868155
TI  - Isolation of Mycoplasma hominis from extragenital cultures.
AB  - In order to document the characteristics of extragenital Mycoplasma hominis
      infections, the clinical features of 36 cases in which M. hominis was isolated
      from extragenital sites of adult patients were reviewed. In most cases, the
      organism was detected in conventional bacterial cultures (from specimens obtained
      from surgical and immunosuppressed patients) that had been incubated for at least
      72 h. The results indicate that in cases in which M. hominis involvement is
      suspected, prolonged incubation or specialized microbiological techniques for
      detecting Mycoplasma spp. should be employed.

PMID- 15868156
TI  - An outbreak of Q fever in an urban area in Israel.
AB  - Reported here is an outbreak of 21 cases of Q fever that were diagnosed during 5
      months in the spring and summer of 2001 at Rambam Medical Center, Haifa, Israel.
      An epidemiological investigation and a case-control study were conducted to
      identify risk factors associated with acquisition of the disease in this
      outbreak. Patients were more likely than controls to live in Krayot (a large
      suburb of Haifa) (76.2% vs. 41.5%; p=0.005), to have more contact with animals
      (usually pets) (66.7% vs. 26.9%; p=0.007), and to consume more unpasteurized
      dairy products (23.8% vs. 0%; p=0.01). The Krayot suburb is an entirely urban
      area, but several livestock facilities are located in its close vicinity, and
      some of them have been reported to harbor Q fever. Although the patients did not
      recall having had direct contact with farm animals, the results suggest the
      presence of livestock facilities in such close proximity to a residential area
      may cause urban outbreaks of Q fever.

PMID- 15868157
TI  - Pseudomonas aeruginosa, Candida albicans, and device-related nosocomial
      infections: implications, trends, and potential approaches for control.
AB  - For many years, device-associated infections and particularly device-associated
      nosocomial infections have been of considerable concern. Recently, this concern
      was heightened as a result of increased antibiotic resistance among the common
      causal agents of nosocomial infections, the appearance of new strains which are
      intrinsically resistant to the antibiotics of choice, and the emerging
      understanding of the role biofilms may play in device-associated infections and
      the development of increased antibiotic resistance. Pseudomonas aeruginosa and
      Candida albicans are consistently identified as some of the more important agents
      of nosocomial infections. In light of the recent information regarding device
      associated nosocomial infections, understanding the nature of P. aeruginosa and
      C. albicans infections is increasingly important. These two microorganisms
      demonstrate: (1) an ability to form biofilms on the majority of devices employed
      currently, (2) increased resistance/tolerance to antibiotics when associated with
      biofilms, (3) documented infections noted for virtually all indwelling devices,
      (4) opportunistic pathogenicity, and (5) persistence in the hospital environment.
      To these five demonstrated characteristics, two additional areas of interest are
      emerging: (a) the as yet unclear relationship of these two microorganisms to
      those species of highly resistant Pseudomonas spp and Candida spp that are of
      increasing concern with device-related infections, and (b) the recent research
      showing the dynamic interaction of P. aeruginosa and C. albicans in patients with
      cystic fibrosis. An understanding of these two opportunistic pathogens in the
      context of their ecosystems/biofilms also has significant potential for the
      development of novel and effective approaches for the control and treatment of
      device-associated infections.

PMID- 15868159
TI  - Laboratory evaluation of oil spill bioremediation products in salt and freshwater
      systems.
AB  - Ten oil spill bioremediation products were tested in the laboratory for their
      ability to enhance biodegradation of weathered Alaskan North Slope crude oil in
      both freshwater and saltwater media. The products included nutrients to stimulate
      inoculated microorganisms, nutrients plus an oil-degrading inoculum, nutrients
      plus compounds intended to stimulate oil-degrading activity, or other compounds
      intended to enhance microbial activity. The product tests were undertaken to
      evaluate significant modifications in the existing official United States
      Environmental Protection Agency (EPA) protocol used for qualifying commercial
      bioremediation agents for use in oil spills. The EPA protocol was modified to
      include defined formulas for the exposure waters (freshwater, saltwater), a
      positive control using a known inoculum and nutrients, two negative controls (one
      sterile, the other inoculated but nutrient-limited), and simplified oil chemical
      analysis. Three analysts conducted the product test independently in each type of
      exposure water in round-robin fashion. Statistical tests were performed on
      analyst variability, reproducibility, and repeatability, and the performance of
      the various products was quantified in both exposure media. Analysis of variance
      showed that the analyst error at each time-point was highly significant (P values
      ranged from 0.0001 to 0.008, depending on water type and oil fraction). In the
      saltwater tests, six products demonstrated various degrees of biodegradative
      activity against the alkane fraction of the crude oil and three degraded the
      aromatic hydrocarbons by >10%. In the freshwater tests, eight products caused
      >20% loss of alkane hydrocarbons, of which five degraded the alkanes by >50%.
      Only four products were able to degrade polycyclic aromatic hydrocarbons (PAHs)
      by >20%, one of which caused 88% removal. However, when the variability of the
      analysts was taken into consideration, only one of the ten products was found to
      yield significant percent removals of the PAH fraction and only in freshwater.
      Viable microorganism population analysis (most-probable-number method) was also
      performed on every sample by each operator to measure the changes in aromatic and
      alkane hydrocarbon-degrading organism numbers. In general, little evidence of
      significant growth of either alkane- or PAH-degraders occurred among any of the
      ten products in either the saltwater or freshwater testing.

PMID- 15868160
TI  - Effects of carotenoid availability during laying on reproduction in the blue tit.
AB  - Carotenoids are antioxidant pigments involved in several physiological processes
      and signalling in animals that cannot synthesise them and therefore must acquire
      them from food. We experimentally investigated the effects of carotenoid
      availability in the diet during egg laying on antioxidant deposition in egg yolk
      and the related effects on nestling condition, female body condition and parental
      investment in the blue tit (Parus caeruleus). Carotenoid supplementation of egg
      laying females resulted in a significant increase in carotenoid concentration in
      egg yolk, but not in vitamin E or A concentration. There was no relationship
      between yellow plumage colour of adult females and carotenoid deposition in eggs,
      and no differential effect of feeding treatment depending on female colour.
      Nestlings from eggs laid by carotenoid supplemented females had longer tarsi, had
      faster development of the immune system as reflected by leukocyte concentration
      in blood, and grew brighter yellow feathers than nestlings from control females.
      However, nestlings from the two groups did not differ significantly in body mass,
      plasma antioxidants or plumage colour hue. At the time of chick rearing,
      carotenoid-fed females had increased plasma vitamin E levels compared to
      controls. However, females from the two treatment groups did not differ
      significantly in body condition or feeding rate. These results suggest that
      carotenoid availability is limiting during egg laying, and that females may have
      to balance the benefits of investing in egg quality against the potential costs
      of impairing their own future antioxidant protection. In addition, there may be
      considerable variation in carotenoid availability not only across seasons, but
      also among different stages of the breeding season.

PMID- 15868161
TI  - An experimental test of the evolution of increased competitive ability hypothesis
      in goldenrod, Solidago gigantea.
AB  - The mechanisms that allow introduced plants to become invasive are poorly
      understood. Here, we present a test of the evolution of increased competitive
      ability hypothesis, which holds that because specialized natural enemies may be
      absent from the introduced range, exotic plants may evolve to invest less in anti
      herbivore defenses and thereby gain a competitive advantage over native plants.
      We grew Solidago gigantea plants derived from both the native range (North
      America) and the invasive range (Europe) in a common garden in the native range
      for 2 years. Half the plants were treated with insecticide to protect them from
      insect herbivores and the other half were exposed to insects that colonized the
      garden from nearby fields. Insect herbivore biomass was significantly higher on
      European plants than US plants in the first year but not the second. European
      plants were more heavily attacked by pathogens in both years of the study. When
      exposed to insect herbivores, US plants produced more seed than European plants,
      but when plants were protected from herbivores, seed production was equivalent
      between US plants and European plants. The presence of insect herbivores
      suppressed seed production of European plants much more than that of US plants,
      even though the level of herbivory experienced by European and US plants was
      similar in the second year, suggesting that the ability to tolerate herbivory was
      diminished in European plants. These results partially support the EICA
      hypothesis: plants from the introduced range were more susceptible to some
      natural enemies and benefited more from insect removal than plants from the
      native range. The prediction that European plants would perform better than US
      plants in the absence of insect herbivores was not supported.

PMID- 15868162
TI  - Off-season uptake of nitrogen in temperate heath vegetation.
AB  - In this field study we show that temperate coastal heath vegetation has a
      significant off-season uptake potential for nitrogen, both in the form of
      ammonium and as glycine, throughout winter. We injected 15N-ammonium and 15N
      2x(13C)-glycine into the soil twice during winter and once at spring. The winter
      temperatures were similar to those of an average winter in the northern temperate
      region of Europe, with only few days of soil temperatures below zero or above 5
      degrees C. The vegetation, consisting of the evergreen dwarf shrub Calluna
      vulgaris, the deciduous dwarf shrub Salix arenaria, and the graminoids Carex
      arenaria and Deschampsia flexuosa, showed high root uptake of both forms of
      nitrogen, both 1 day after labelling and after a month, in species specific
      temporal patterns. Plant uptake of 13C was not significant, providing no further
      evidence of intact uptake of glycine. Translocation of the labelled nitrogen to
      shoots was generally evident after 1 month and increased as spring approached,
      with different translocation strategies in the three plant functional types.
      Furthermore, only the graminoids showed shoot growth during winter. Increasing
      plant nitrogen concentration from fall to spring at temperate heaths may, hence,
      be due to nitrogen uptake. Our results suggest that the potential for nitrogen
      uptake in plants at winter is of the same order of magnitude as at summer. Hence,
      winter nitrogen uptake in ecosystems in the temperate/boreal region should be
      considered when making annual nitrogen budgets of heath ecosystems, and the view
      of plant nutrient uptake as low in this climatic region during winter should be
      revised.

PMID- 15868163
TI  - Association between tree-ring and needle delta13C and leaf gas exchange in Pinus
      halepensis under semi-arid conditions.
AB  - Associations between delta13C values and leaf gas exchanges and tree-ring or
      needle growth, used in ecophysiological compositions, can be complex depending on
      the relative timing of CO2 uptake and subsequent redistribution and allocation of
      carbon to needle and stem components. For palaeoenvironmental and
      dendroecological studies it is often interpreted in terms of a simple model of
      delta13C fractionation in C3 plants. However, in spite of potential complicating
      factors, few studies have actually examined these relationships in mature trees
      over inter- and intra-annual time-scales. Here, we present results from a 4 years
      study that investigated the links between variations in leaf gas-exchange
      properties, growth, and dated delta13C values along the needles and across tree
      rings of Aleppo pine trees growing in a semi-arid region under natural conditions
      or with supplemental summer irrigation. Sub-sections of tissue across annual
      rings and along needles, for which time of formation was resolved from growth
      rate analyses, showed rapid growth and delta13C responses to changing
      environmental conditions. Seasonal cycles of growth and delta13C (up to
      approximately 4 per thousand) significantly correlated (P < 0.01) with
      photosynthetically active radiation, vapour pressure deficit, air temperature,
      and soil water content. The irrigation significantly increased leaf net
      assimilation, stomatal conductance and needle and tree-ring growth rate, and
      markedly decreased needle and tree-ring delta13C values and its sensitivity to
      environmental parameters. The delta13C estimates derived from gas-exchange
      parameters, and weighted by assimilation, compared closely with seasonal and
      inter-annual delta13C values of needle- and tree-ring tissue. Higher stomatal
      conductances of the irrigated trees (0.22 vs. 0.08 mol m(-2) s(-1) on average)
      corresponded with approximately 2.0 per thousand lower average delta13C values,
      both measured and derived. Derived and measured delta13C values also indicated
      that needle growth, which occurs throughout the stressful summer was supported by
      carbon from concurrent, low rate assimilation. For Aleppo pine under semi-arid
      and irrigated conditions, the delta13C of tree-ring and needle material proved,
      in general, to be a reasonable indicator of integrated leaf gas-exchange
      properties.

PMID- 15868164
TI  - Cross-fostering reveals an effect of spleen size and nest temperatures on immune
      responses in nestling European starlings.
AB  - Immunocompetence may be a good measure of offspring quality, however, factors
      affecting variation in immune responses are not clear. Research suggests that
      immune function can vary due to differences in genetics, development conditions
      and individual quality. Here, I examined factors affecting variation in immune
      response among nestling European starlings through a split-nest cross-fostering
      brood manipulation that included two important covariates: spleen size and nest
      temperatures. Immunocompetence was assessed via a cell-mediated immune response
      to phytohaemagglutinin (PHA). This paper provides the first direct evidence that
      individuals with large spleens also mount strong immune responses. Exposure to
      PHA did not cause splenomegaly, as there was no difference in spleen size between
      control birds and those injected with PHA. Offspring immune function was affected
      by common origin and by rearing environment, though rearing environment appeared
      to exert its influence only through nest temperatures. A comparison of the immune
      performance of siblings reared in their home nest versus those reared in other
      nests revealed a strong effect of maternal quality. As the difference in natal
      clutch size increased, the magnitude of the difference in immune performance
      between home-reared nestlings versus out-reared nestlings increased. Overall,
      nestling immune function appears to be determined by the combination of genetic,
      maternal and environmental effects.

PMID- 15868165
TI  - Modulation of relative growth rate and its components by water stress in
      Mediterranean species with different growth forms.
AB  - Effects of water availability on seedling growth were analysed in eight
      Mediterranean species naturally occurring in the Balearic Islands. Seedlings were
      grown outdoors during summer under two irrigation treatments: field capacity and
      35% of field capacity. The relative growth rate (RGR) strongly depended on the
      growth form, from highest values in herbs to lowest in woody perennials. The main
      component associated with interspecific variation in RGR was the specific leaf
      area (SLA), and a quantitative grouping of the different growth forms appeared
      along the regression line between both parameters. The slow-growing species, i.e.
      woody perennial shrubs, had the lowest SLA and the fast-growing perennial herbs,
      the highest, while woody semi-deciduous shrubs appeared intermediate. Decreases
      in RGR due to water stress were analysed in terms of the relative contribution of
      the leaf mass ratio (LMR), SLA and the net assimilation rate (NAR). Pooling all
      species, the decrease in RGR caused by water deficit was mainly explained by
      decreases in SLA. However, this general pattern was strongly dependent of growth
      form. Thus, in the woody perennial plants, the decrease in RGR was accompanied by
      a three-fold decrease in NAR which, however, increased in perennial herbs. SLA
      increased with decreasing water supply in woody perennial plants, and decreased
      in woody semi-deciduous shrubs and perennial herbs. Finally, decreases in LMR
      partly explained decreases in RGR in perennial herbs and woody perennial shrubs.
      This different response of the different growth forms may reflect differences in
      seedling adaptation and surviving strategies to drought periods.

PMID- 15868166
TI  - Combination therapy using the cyclooxygenase-2 inhibitor Parecoxib and
      radioimmunotherapy in nude mice with small peritoneal metastases of colonic
      origin.
AB  - BACKGROUND: Inhibition of the COX-2 enzyme has been shown to have a
      radiosensitizing effect in epithelial cancers. The aim of this study was to
      investigate whether the efficacy of radioimmunotherapy (RIT) using 131I-labeled
      anti-CEA monoclonal antibody MN-14 could be enhanced by co-administration of the
      selective COX-2 inhibitor Parecoxib in mice with small volume (1-3 mm) peritoneal
      carcinomatosis of colonic origin. METHODS: First, the efficacy of 14 daily
      injections of Parecoxib monotherapy (0-0.2-1.0-5.0-25.0 mg/kg) was determined in
      mice with intraperitoneal LS174T xenografts. Second, the influence of Parecoxib
      (1.0 or 5.0 mg/kg) on the biodistribution of 125I-MN-14 was assessed. Finally,
      the efficacy of RIT alone [125 microCi 131I-MN-14/mouse approximately 1/4 of the
      maximal tolerated dose (MTD)] was compared with that of Parecoxib monotherapy and
      RIT combined with daily injections of Parecoxib (1.0 or 5.0 mg/kg). RESULTS:
      Parecoxib had no measurable antitumor effect up to the highest dose level (25
      mg/kg). Parecoxib had no effect on the uptake of 125I-MN-14 in the
      intraperitoneal tumor xenografts or on normal tissue distribution. Median
      survival of the control mice and the mice treated with Parecoxib monotherapy (1.0
      or 5.0 mg/kg) was 48.5 days, 52 days and 52 days (P=0.47). RIT alone
      significantly delayed the growth of the intraperitoneal xenografts resulting in a
      median survival of 87 days (P<0.0001). Mice treated with RIT + Parecoxib at 1.0
      or 5.0 mg/kg had a median survival of 73.5 days and 76 days, respectively, which
      was not statistically different from survival after RIT alone (P=0.15).
      CONCLUSION: The COX-2 inhibitor Parecoxib does not enhance the therapeutic
      efficacy of RIT of experimental small volume peritoneal carcinomatosis of colonic
      origin.

PMID- 15868167
TI  - Regulatory T cells and tumor immunity.
AB  - Central deletion of "self-reactive" T cells has been the textbook paradigm for
      inducing "self-tolerance" in the periphery and the concept of a role of T cell
      mediated suppression in this process has long been controversial. A decisive
      shift in the opinion on suppressor T cells has lately occurred with the
      observations of Sakaguchi's group that linked a class of CD4+CD25+ T cells to the
      prevention of autoimmunity from neonatal thymectomy in mice. These CD4+CD25+ T
      cells have been named T regulatory (Treg) cells. They are believed to be selected
      in the thymus as an anti-self repertoire. Hence they were referred to as natural
      T regulatory (nTreg) cells. Presently, in addition to their role in autoimmunity,
      they are believed to exert regulatory function in infection, in transplantation
      immunity as well as in tumor immunity. In contrast to these nTreg cells, another
      class of CD4+ Treg cells also exercises regulatory function in the periphery.
      These Treg cells are also CD4+ T cells and after activation they also become
      phenotypically CD4+CD25+. They are, however induced in the periphery as Treg
      cells. Hence, they are termed as induced Treg (iTreg) cells. There are major
      differences in the biology of these two types of Treg cells. They differ in their
      requirements for activation and in their mode of action. Nonetheless, evidence
      indicates that both nTreg cells and iTreg cells are involved in the control of
      tumor immunity. The question of how to circumvent their regulatory constraints,
      therefore, has become a major challenge for tumor immunologists.

PMID- 15868168
TI  - Expression of complement protein C5a in a murine mammary cancer model: tumor
      regression by interference with the cell cycle.
AB  - The C5a anaphylatoxin protein plays a central role in inflammation associated
      with complement activation. This protein is commonly regarded as one of the most
      potent inducers of the inflammatory response and a C5a peptide agonist was used
      as a molecular adjuvant. However, the full length C5a protein has not been tested
      as a potential tumor therapy. In this report, we describe the creation of a mini
      gene construct that directs C5a expression to any cell of interest. Functional
      expression could be demonstrated in the murine mammary sarcoma, EMT6. When C5a
      expressing cells were injected into syngeneic mice, most C5a-expressing clones
      had significantly reduced tumor growth. Further characterization of a clone
      expressing low levels of C5a demonstrated that one-third of mice injected with
      this line had complete tumor regression. The mice whose tumors regressed were
      immune to subsequent challenge with unmodified EMT6 cells, suggesting that a
      component of the innate immune response can be used to augment adaptive immunity.
      Cellular analyses demonstrated that a significant difference in actual tumor cell
      number could be detected as early as day 10. A block in cell cycle progression
      was evident at all time points and high levels of apoptosis were observed early
      in the regression event. These data demonstrate that the complement protein C5a
      can play a significant protective role in tumor immunity.

PMID- 15868169
TI  - Congenital pouch colon with prune belly syndrome and megalourethra.
AB  - Congenital pouch colon (CPC), an unusual high anorectal malformation in which a
      varying length of colon is replaced by a dilated pouch, has appeared in a number
      of case reports and series published in the English literature. There is only one
      case report of its association with prune belly syndrome (also known as triad
      syndrome, Eagle-Barrett syndrome, and abdominal muscle deficiency syndrome). We
      report the description and management of this rare association in a male neonate
      with CPC, prune belly syndrome, and congenital megalourethra.

PMID- 15868170
TI  - Clival chordoma manifesting as nasal bleeding. A case report.
AB  - Chordoma is a rare cartilaginous tumor, for which bleeding presentation is
      unusual. We report a case of rare hemorrhaged clival chordoma, which was
      diagnosed correctly by magnetic resonance imaging. A 32-year-old man presented
      with nasal bleeding. The tumor was totally removed via a trans-sphenoidal
      approach, from which the surgical specimen confirmed chordoma. Epistaxis seemed
      to be caused by the spreading of the intratumoral hemorrhage into the sphenoid
      sinus. This case demonstrates the importance of an exact differential diagnostic
      evaluation, including chordoma, by use of modern imaging techniques for nasal
      bleeding.

PMID- 15868171
TI  - A contribution to the controversy over dimethyl sulfoxide toxicity: anesthesia
      monitoring results in patients treated with Onyx embolization for intracranial
      aneurysms.
AB  - Onyx injection is a new technique for embolization of cerebral aneurysms that is
      involved in a controversy about the 'toxicity' of its solvent, dimethyl sulfoxide
      (DMSO). We retrospectively studied 38 patients treated for aneurysms with the
      liquid polymer, Onyx. Induction was with propofol, fentanyl and vecuronium, and
      anesthesia was maintained with isoflurane in O2 and N2O. The patients were given
      500 ml of fluid after induction, and bradycardia was prevented in order to keep
      patients hyperdynamic. Electrocardiography (ECG), non-invasive blood pressure
      (NIBP), pulse oximetry, core temperatures, invasive blood pressure (BP), etCO2,
      and urine output were monitored throughout the intervention. Heart rate and BP
      changes in response to balloon inflation, DMSO injection, Onyx injection and
      balloon deflation were recorded. The patients were followed with serial
      neurological examinations, computerized tomography and/or magnetic resonance
      imaging postoperatively for evidence of any neurological injury. Cumulative DMSO
      doses were always well under previously implicated doses for systemic toxicity.
      No changes implicating toxic reactions were observed during DMSO and Onyx
      injections. Balloon-induced changes returned to baseline within 1 min of balloon
      deflation. Technique-related permanent morbidity occurred in two patients
      (worsening of cranial nerve palsies in one and monocular blindness in another)
      and intracranial hemorrhage with resulting death in one patient. All patients
      showed a tendency to oxygen desaturation, but this finding did not cause any
      clinical consequence. Anesthesiologists need to be vigilant in monitoring
      patients treated with techniques that are new or are being developed. We have
      seen no evidence of toxicity or any anesthetic complications in our group of
      patients, our only clinical concern being a tendency to oxygen desaturation,
      which may be explained by the inhalational elimination of DMSO.

PMID- 15868172
TI  - Unilateral agenesis and hypoplasia of the internal carotid artery: a report of
      three cases.
AB  - We report one patient with agenesis and two with hypoplasia of the internal
      carotid artery (ICA) from an angiographic series of 1275 consecutive patients. In
      all three patients, MRI and MR angiography were used to establish the anatomical
      situation; however, they may not clearly distinguish between hypoplasia and
      agenesis or acquired stenosis or occlusion of the ICA. In such cases, CT of the
      skull base may be obtained to clarify matters. In all patients, retrograde flow
      via a large posterior communicating artery was demonstrated. Single-photon
      emission computed tomography confirmed both the adequacy of cerebral perfusion
      and the preservation of vasomotor reactivity.

PMID- 15868173
TI  - Changes in head and neck position affect elbow joint position sense.
AB  - Changes in the position of the head and neck have been shown to introduce a
      systematic deviation in the end-point error of an upper limb pointing task.
      Although previous authors have attributed this to alteration of perceived target
      location, no studies have explored the effect of changes in head and neck
      position on the perception of limb position. This study investigated whether
      changes in head and neck position affect a specific component of movement
      performance, that is, the accuracy of joint position sense (JPS) at the elbow.
      Elbow JPS was tested with the neck in four positions: neutral, flexion, rotation
      and combined flexion/rotation. A target angle was presented passively with the
      neck in neutral, after a rest period; this angle was reproduced actively with the
      head and neck in one of the test positions. The potential effects of distraction
      from head movement were controlled for by performing a movement control in which
      the head and neck were in neutral for the presentation and reproduction of the
      target angle, but moved into flexion during the rest period. The absolute and
      variable joint position errors (JPE) were greater when the target angle was
      reproduced with the neck in the flexion, rotation, and combined flexion/rotation
      than when the head and neck were in neutral. This study suggests that the reduced
      accuracy previously seen in pointing tasks with changes in head position may be
      partly because of errors in the interpretation of arm position.

PMID- 15868174
TI  - Hitting moving targets: effects of target speed and dimensions on movement time.
AB  - To hit moving targets, one not only has to arrive at the right place but also at
      the right time. Moving quickly reduces spatial precision but increases temporal
      precision. This may explain why people usually move more quickly toward fast
      targets than toward slow ones, because arriving at the right time is more
      important when hitting fast targets. The temporal accuracy required depends not
      only on the target's speed but also on its length in the direction of motion; it
      decreases with increasing length. Here we investigate the effects of variations
      in the target's speed and dimensions on the subject's movement time. We asked
      subjects to hit targets that moved from left to right as quickly as possible with
      their index finger. The targets varied in length in the direction of motion
      (width: affecting both spatial and temporal demands), in length in the orthogonal
      direction (height: affecting spatial demand), and in speed (affecting temporal
      demand). Targets were presented in random order during one session and in blocks
      of trials with identical targets during another session. In the latter session
      subjects could optimize their strategy for each target separately. In the random
      condition subjects hit fast targets more quickly than slow ones. Their movement
      time was also affected by the target's size (the spatial demand), but not by the
      direction of the elongation. For the blocked condition, subjects did consider the
      direction of the elongation. We conclude that people do not consider an object's
      orientation to estimate the temporal demands of an interception task, but that
      they use the object's size and speed, and their experience from previous trials.

PMID- 15868175
TI  - Orientation-specific fast rTMS maximizes corticospinal inhibition and
      facilitation.
AB  - Specific stimulation of neuronal circuits may promote selective inhibition or
      facilitation of corticospinal tract excitability. Monophasic stimulation is more
      likely to achieve direction-specific neuronal excitation. In 10 healthy subjects,
      we compared four types of repetitive transcranial magnetic stimulation (rTMS),
      monophasic and biphasic stimuli with the initial current in the brain flowing
      antero-posteriorly ("posteriorly directed") or postero-anteriorly ("anteriorly
      directed"). We applied rTMS over the primary motor cortex contralateral to the
      dominant hand, using 80 stimuli at 5 Hz frequency at an intensity yielding
      baseline motor evoked potential (MEP) amplitudes of 1 mV. Monophasic stimulation
      was always more efficient than biphasic. Facilitation was induced by
      intracerebral anteriorly directed current flow and inhibition by posteriorly
      oriented current flow, although only initially for approximately 30 pulses. The
      early inhibition was absent when studied during a tonic muscle contraction.
      Several mechanisms could account for these findings. They include a more
      efficient excitation of inhibiting circuits by posteriorly oriented pulses, and a
      back-propagating D-wave inhibiting early I-waves and thus inducing early
      inhibition of MEP amplitude. In any case biphasic rTMS results can be explained
      by a mixture of monophasic opposite stimulations. We propose the use of
      monophasic pulses for maximizing effects during rTMS.

PMID- 15868176
TI  - Jaw movement alters the reaction of human jaw muscles to incisor stimulation.
AB  - The changes in the minimum time to consciously react (reaction time) and the
      order of jaw muscle recruitment to precisely controlled axial stimulation of the
      incisors during controlled jaw movements are not known. To this end, ten subjects
      were recruited to investigate the reaction time of bilateral temporalis and
      masseter muscles and bite force. Stimuli were delivered axially to the upper
      central incisors during active jaw closing and opening, and under static
      conditions. The results showed that the reaction time was increased an average of
      35% during both jaw opening and closing movements when compared with static jaw
      conditions. The left temporalis was recruited approximately 10 ms before the
      right temporalis, whereas no significant side differences were found between the
      masseter muscles. The masseter muscles were recruited an average of 20 ms before
      the temporalis muscles during jaw closing, but no difference existed during
      opening. Under static conditions the reaction time in the bite force was
      approximately 16 ms longer than the left temporalis, but was not significantly
      different from the reaction time of any of the other muscles, indicating that,
      under the static conditions tested, the left temporalis was more often
      responsible for initiation of the mechanical reactions in the jaw. Because of
      active compensation, no force measurements were made during jaw movement. This
      study is a prerequisite for investigations into the modulation of reflexes during
      jaw movement, because a response to a stimulus commencing after the minimum
      reaction time may not be entirely reflex in origin.

PMID- 15868177
TI  - [The Anaesthesiological Questionnaire for patients in cardiac anaesthesia.
      Results of a multicenter survey by the scientific working group for cardiac
      anaesthesia of the German Society for Anaesthesiology and Intensive Care
      Medicine].
AB  - OBJECTIVE: The Anaesthesiological Questionnaire (ANP) is a self-rating method for
      the assessment of postoperative complaints and patient satisfaction. The
      questionnaire was adapted for use in cardiac anaesthesia (ANP-KA). The study was
      conducted to show the value of ANP-KA as a practicable means of assessing the
      patient's state after cardiac anaesthesia and for its use in quality assurance.
      METHODS: A total of 1,688 patients from 19 clinics were included who had
      exclusively received heart valve surgery, CABG surgery or both operations. They
      completed the ANP-KA between days 1 and 8 postoperatively. RESULTS: The ANP-KA
      was completed by 79.1% of the patients without any assistance. The highest
      incidence rates were reported for a dry mouth/thirst (85.1%) and for pain in the
      area of surgery (60.2%). Plausible and significant differences in patients'
      symptoms between the grading for the immediate postoperative period and the
      current state at filling in the questionnaire were found. Women reported more
      postoperative complaints than men but no differences were found between male and
      female patients with regard to satisfaction with anaesthesiological care and
      convalescence. More complaints were reported after heart valve surgery than after
      CABG and satisfaction with convalescence was significantly lower after heart
      valve surgery. The clinics differed with respect to the reported somatic
      complaints and satisfaction scales. CONCLUSION: The results demonstrate the
      practicability and validity of the ANP-KA for the assessment of postoperative
      complaints and patient satisfaction after cardiac surgery.

PMID- 15868179
TI  - Formation and maturation of olfactory cilia monitored by odorant receptor
      specific antibodies.
AB  - The responsiveness of olfactory sensory neurons (OSNs) is based on odorant
      receptors (ORs) residing in the membrane of chemosensory cilia. It is still
      elusive as to when and how olfactory cilia are equipped with OR proteins
      rendering them responsive to odorants. To monitor the appearance of OR proteins
      in sensory compartments of OSNs, the olfactory epithelium of mice at various
      stages of prenatal development (lasting 19 days from conception) was investigated
      using immunohistochemical approaches and antibodies specific for different OR
      subtypes. These experiments uncovered that OR proteins accumulated in dendritic
      knobs of OSNs before the initiation of ciliogenesis (embryonic stage E12). As the
      first cilia were formed (E13), immunostaining in the knobs diminished. Cilia
      extended uprightly into the nasal cavity and were immunoreactive along the entire
      length, and particularly intense labeling was observed in expanded tips of cilia.
      During this phase of development (up to E18), the number of cilia per knob
      continuously increased. In the course of perinatal stages, longer cilia began to
      bend off and lie flat on the epithelial surface. The multiple cilia of a knob
      extended in length, and eventually the ciliary "meshwork" reached the
      characteristic complex pattern. In all stages, OR immunostaining was visible
      along the entire cilium. Thus, OR-specific antibodies allowed, for the first
      time, monitoring at the level of light microscopy the generation, outgrowth, and
      maturation of cilia in OSNs.

PMID- 15868180
TI  - Tissue distribution of the "N-end rule" ubiquitin-conjugating enzyme, HR6, in the
      rat.
AB  - The conjugation of multiple ubiquitin molecules is required for recognition and
      degradation of a protein by the proteasome. The ubiquitination pathway
      responsible for the bulk of constitutive protein degradation targets proteins
      carrying basic or large hydrophobic amino acids at the N-terminus. In mammalian
      cells, this "N-end rule" pathway requires the ubiquitin-conjugating enzyme HR6.
      Until now, it has not been known which mammalian tissues and cell types
      predominantly utilize this pathway for degradation. Therefore, the distribution
      and intracellular localization of HR6 was determined by indirect
      immunofluorescence techniques and protein blotting of adult rat tissues. Intense
      immunoreactivity against HR6 was detected in various epithelia, muscle, testis,
      peripheral neurons, chromaffin cells and macrophages, whereas lower HR6 protein
      levels were found in the gut or in the kidney. Autonomic and sensory neurons,
      glandular cells and spermatocytes revealed prominent nuclear HR6
      immunoreactivity. Plasma membrane labeling was observed in peripheral neurons,
      spermatocytes and skeletal muscle cells. Smooth muscle cells, macrophages,
      endothelial and epithelial cells exhibited primarily cytoplasmic staining. The
      clear differences in the regional and intracellular distribution of HR6 are
      suggestive for the involvement of N-end rule protein degradation in various
      physiological processes dependent on cell type and subcellular structure.

PMID- 15868181
TI  - Urothelial injuries and the early wound healing response: tight junctions and
      urothelial cytodifferentiation.
AB  - Using primary explant cultures of mouse bladder, the early response of the
      urothelium after superficial and full-thickness injuries was investigated. In
      such an in vitro wound healing model, explant surfaces with a mostly desquamated
      urothelial superficial layer represented superficial wounds, and the exposed
      lamina propria at the cut edges of the explants represented full-thickness
      wounds. The urothelial cell ultrastructure, the expression and subcellular
      distribution of the tight junctional protein occludin, and differentiation
      related proteins CK 20, uroplakins, and actin were followed. Since singular
      terminally differentiated superficial cells remained on the urothelium after
      superficial injury (i.e., original superficial cells), we sought to determine
      their role during the urothelial wound-healing process. Ultrastructural and
      immunocytochemical studies have revealed that restored tight junctions are the
      earliest cellular event during the urothelial superficial and full-thickness
      wound-healing process. Occludin-containing tight junctions are developed before
      the new superficial cells are terminally differentiated. New insights into the
      urothelium wound-healing process were provided by demonstrating that the original
      superficial cells contribute to the urothelium wound healing by developing tight
      junctions with de novo differentiated superficial cells and by stretching, thus
      providing a large urothelial surface with asymmetric unit membrane plaques.

PMID- 15868182
TI  - An under-recognised malposition of neonatal long lines.
AB  - We report two cases of malposition of percutaneous central venous catheters into
      the left ascending lumbar vein. The level of awareness amongst clinicians of this
      potentially fatal complication appears to be low. CONCLUSION: The recognition of
      unusual patterns of contrast medium dispersal is important in the diagnosis of
      catheter malposition.

PMID- 15868183
TI  - Reduction of ferricytochrome c by tyrosyltyrosylphenylalanine.
AB  - Cytochrome c (cyt c) was reduced by a tyrosine-containing peptide,
      tyrosyltyrosylphenylalanine (TyrTyrPhe), at pH 6.0-8.0, while tyrosinol or
      tyrosyltyrosine (TyrTyr) could not reduce cyt c effectively under the same
      condition. Cyt c was reduced at high peptide concentration, whereas the reaction
      did not occur effectively at low concentration. The reaction rate varied with
      time owing to a decrease in the TyrTyrPhe concentration and the production of
      tyrosine derivatives during the reaction. The initial rate constants were 2.4 x
      10(-4) and 8.1 x 10(-4) s(-1) at pH 7.0 and 8.0, respectively, for the reaction
      with 1.0 mM TyrTyrPhe in 10 mM phosphate buffer at 15 degrees C. The reciprocal
      initial rate constant (1/k(int)) increased linearly against the reciprocal
      peptide concentration and against the linear proton concentration, whereas
      logk(int) decreased linearly against the root of the ionic strength. These
      results show that deprotonated (TyrTyrPhe)(-), presumably deprotonated at a
      tyrosine site, reduces cyt c by formation of an electrostatic complex. No
      significant difference in the reaction rate was observed between the reaction
      under nitrogen and oxygen atmospheres. From the matrix-assisted laser desorption
      ionization time-of-flight mass spectra of the reaction products, formation of a
      quinone and other tyrosine derivatives of the peptide was supported. These
      products should have been produced from a tyrosyl radical. We interpret the
      results that a cyt c(ox)/(TyrTyrPhe)(-)right harpoon over left harpooncyt
      c(red)/(TyrTyrPhe)(*) equilibrium is formed, which is usually shifted to the
      left. This equilibrium may shift to the right by reaction of the produced tyrosyl
      radical with the tyrosine sites of unreacted TyrTyrPhe peptides.

PMID- 15868184
TI  - Idiopathic facial paralysis (Bell's palsy) in the immediate puerperium in a
      patient with mild preeclampsia: a case report.
AB  - INTRODUCTION: Idiopathic peripheral facial palsy is the most common and frequent
      unilateral cranial neurological disorder characterized by an isolated facial
      nerve paralysis. CASE REPORT: We report a case of an idiopathic facial paralysis
      (Bell's palsy) in the immediate puerperium in a patient with mild preeclampsia
      and diagnosed fetal IUGR. Additionally, the presence of Bell's palsy in the
      puerperium of the mother of our patient suggests a familiar tendency. DISCUSSION:
      Every gynaecologist and obstetrician should be aware of this quite uncommon
      complication during pregnancy and the puerperium. This case report illustrates
      that Bell's palsy can occur in the immediate post-partum after mild preeclamptic
      symptoms. For these women, a maternal surveillance can be recommended. A fast and
      accurate diagnosis with a subsequent immediate treatment might be very important
      in avoiding worsening of the symptoms and therefore improve the recovery
      prognosis.

PMID- 15868185
TI  - Is telomere length one of the determinants of reproductive life span?
AB  - The mechanism of final cessation of the reproductive life span has not been
      solved yet. It is generally assumed that the most important factor is ovarian
      follicular reserve. In ovaries at intrauterine period, a major factor that
      determines the number of the primordial follicle is the mitotic ability as well
      as the number of primordial germ cells, which migrate to gonadal ridge. The
      telomere length is one factor that determines the number of mitosis of the cell.
      The differences between the telomere lengths of same aged healthy women reflect
      the difference of the telomeres of the primordial germ cells at the intrauterine
      period. Women with long telomeres supposedly have had their primordial germ cells
      at the beginning of life with long telomeres. So, these cells should have had
      more mitotic division and more follicle numbers in the ovaries than the short
      ones. The aim of this study was to analyse the relation of the reproductive life
      span and telomere length. The telomere lengths of 37 women volunteers aged 50
      years were measured by fiber FISH technique. A positive correlation was found
      between reproductive life span and the telomere length.

PMID- 15868186
TI  - In vitro stimulation of penetration gland emptying by Trichobilharzia szidati and
      T. regenti (Schistosomatidae) cercariae. Quantitative collection and partial
      characterization of the products.
AB  - Induction of penetration gland emptying by cercariae of the bird schistosomes
      Trichobilharzia szidati and T. regenti employing linoleic acid, linolenic acid,
      praziquantel and calcium ionophore A23187 showed that both postacetabular and
      circumacetabular cells released their content at chosen stimulant concentrations.
      The gland secretions consisted of soluble and insoluble parts. The former one
      adhering to the ground seemed to have different saccharide composition from the
      glands of Schistosoma mansoni. It bound labelled saccharides, thus exhibiting
      lectin-like activity. Protein profiles of the latter one were identical after
      stimulation by all four stimulants in T. szidati. The soluble secretions
      contained several proteolytic enzymes; 31 kDa and 33 kDa cysteine proteases were
      identified in E/S products of T. szidati and T. regenti, respectively. The
      circumacetabular glands contained a significant amount of calcium.
      Immunohistochemistry revealed that the origin of E/S products after in vitro
      stimulation is in both penetration glands and tegumental structures. No
      crossreactivity was observed between the bird schistosomes and a serum raised
      against S. mansoni elastase.

PMID- 15868187
TI  - Identification of immune genes in grass carp Ctenopharyngodon idella in response
      to infection of the parasitic copepod Sinergasilus major.
AB  - The parasitic copepod Sinergasilus major is an important pathogen of grass carp
      Ctenopharyngodon idella. To understand the immune response of grass carp to the
      copepod infection, suppression subtractive hybridization method was employed to
      characterize genes up-regulation during the copepod infection in liver and gills
      of the fish. One hundred and twenty-two dot blot positive clones from infected
      subtracted library were sequenced. Searching available databases by using these
      nucleotide sequences revealed that 23 genes are immune-related, including known
      acute-phase reactants, and four novel genes encoding proteins such as source of
      immunodominant MHC-associated peptides (SIMP), TNF receptor-associated factor 2
      binding protein (T2BP), poliovirus receptor-related protein 1 precursor,
      glycoprotein A repetitions predominant (GARP). The differential expression of
      seven immune genes, i.e. GARP, alpha-2-macroglobulin, MHC class I, C3, SIMP,
      T2BP, transferrin, as a result of infection was further confirmed by RT-PCR, with
      the up-regulation of alpha-2-macroglobulin, MHC class I, C3, SIMP and T2BP in the
      liver of infected fish, and down-regulation of SIMP in the gills of infected
      fish. The present study provides foundation for understanding grass carp immune
      response and candidate genes for further analysis.

PMID- 15868188
TI  - Refractoriness to the treatment of sodium stibogluconate in Indian kala-azar
      field isolates persist in in vitro and in vivo experimental models.
AB  - Ever since their discovery about 60 years ago as therapeutic agent for visceral
      leishmaniasis (VL) or kala-azar, pentavalent antimonials (Sb(v)) have remained
      the first line treatment of choice all over the world including India. But
      recently, the number of kala-azar patients unresponsive to sodium stibogluconate
      (SSG) therapy, is steadily increasing in India. In this study, three clinical
      isolates, of which two were from SSG unresponsive and one from SSG responsive
      patients were evaluated for their infectivity and for their chemotherapeutic
      responses in vitro (macrophage-amastigote system) and in vivo (in hamsters).
      Persistence of SSG resistance was also checked by repeated passages in vitro as
      well as in vivo. The drug resistant strains (2039 and 2041) did not respond to
      SSG therapy both in vitro as well as in vivo but strains 2001 and Dd8 showed full
      sensitivity to SSG treatment. All the four strains responded well to amphotericin
      B and miltefosine treatment both in macrophages and in hamsters. The specific
      chemotherapeutic responses of all the strains to SSG were consistently persistent
      after repeated passages in cultures and in vivo, which indicates that these
      isolates are truly refractory to SSG treatment in field conditions. Two isolates
      were also transfected with green fluorescent protein (GFP) for the development of
      in vitro assay for studying antileishmanial activities of new and reference drugs
      in macrophages by flow cytometry.

PMID- 15868190
TI  - Growth induced curve dynamics for filamentary micro-organisms.
AB  - The growth of filamentary micro-organisms is described in terms of the geometry
      of evolving planar curves in which the dynamics is determined by an underlying
      growth process. Steadily propagating tip shapes in two and three dimensions are
      found that are consistent with experimentally observed growth sequences.

PMID- 15868191
TI  - The dynamical way to mutation-selection balance of an infinite population
      evolving on a truncated fitness landscape.
AB  - This paper presents the exact analytical solution, valid for all generations and
      initial conditions, for the frequency distribution of haploids with infinite
      sites genome carrying a given number of mutations in a population evolving
      deterministically on a truncated fitness landscape. This landscape is a
      generalization of the single sharp peak one, widely used in quasispecies theory,
      although here there are no reverse mutations.

PMID- 15868189
TI  - Cloning and characterization of SK2 channel from chicken short hair cells.
AB  - In the inner ear of birds, as in mammals, reptiles and amphibians, acetylcholine
      released from efferent neurons inhibits hair cells via activation of an apamin
      sensitive, calcium-dependent potassium current. The particular potassium channel
      involved in avian hair cell inhibition is unknown. In this study, we cloned a
      small-conductance, calcium-sensitive potassium channel (gSK2) from a chicken
      cochlear library. Using RT-PCR, we demonstrated the presence of gSK2 mRNA in
      cochlear hair cells. Electrophysiological studies on transfected HEK293 cells
      showed that gSK2 channels have a conductance of approximately 16 pS and a half
      maximal calcium activation concentration of 0.74+/-0.17 microM. The expressed
      channels were blocked by apamin (IC(50)=73.3+/-5.0 pM) and d-tubocurarine
      (IC(50)=7.6+/-1.0 microM), but were insensitive to charybdotoxin. These
      characteristics are consistent with those reported for acetylcholine-induced
      potassium currents of isolated chicken hair cells, suggesting that gSK2 is
      involved in efferent inhibition of chicken inner ear. These findings imply that
      the molecular mechanisms of inhibition are conserved in hair cells of all
      vertebrates.

PMID- 15868192
TI  - Periodic solutions in modelling lagoon ecological interactions.
AB  - In this paper we present and analyze a nutrient-oxygen-phytoplankton-zooplankton
      mathematical model simulating lagoon ecological interactions. We obtain
      sufficient conditions, based on principal eigenvalue criteria -- for the
      existence of periodic solutions. A decoupled model which arises in the high
      nutrient regime is then considered in further detail for gathering some explicit
      conditions on parameters and averages of exogenous inputs needed for coexistence.
      An application to Italian coastal lagoons is finally obtained by parameter
      estimation and comparison with real data. A biological interpretation of the
      mathematical results is also presented.

PMID- 15868193
TI  - Equilibrium state of molecular breeding.
AB  - We investigate the equilibrium state of the model of Peng, et al. for molecular
      breeding. In the model, a population of DNA sequences is successively culled by
      removing the sequences with the lowest binding affinity to a particular target
      sequence. The remaining sequences are then amplified to restore the original
      population size, undergoing some degree of point-substitution of nucleotides in
      the process. Working in the infinite population size limit, we derive an equation
      for the equilibrium distribution of binding affinity, here modeled by the number
      of matches to the target sequence. The equation is then solved approximately in
      the limit of large sequence length, in the three regimes of strong, intermediate
      and weak selection. The approximate solutions are verified via comparison to
      exact numerical results.

PMID- 15868194
TI  - A stochastic model for a progressive chronic disease.
AB  - For many progressive chronic diseases, there exist useful prognostic indicators
      for the course of the disease and the survival of the patient. The evolution of
      such an indicator is modelled as a monotone transformation of a pure birth
      process with killing. Explicit formulas are derived for the probability
      distribution of this process at an arbitrary time, the distribution of the first
      passage times, the joint distribution of the survival time and the maximum of the
      process, and the marginals of this joint distribution. In two examples, the
      general formulas are evaluated in closed form.

PMID- 15868195
TI  - Self-thinning and community persistence in a simple size-structured dynamical
      model of plant growth.
AB  - This paper presents a size-structured dynamical model of plant growth. The model
      takes the form of a partial differential-integral equation and includes the
      effects of self- shading by leaves. Closed form solutions are presented for the
      equilibrium size density distribution. Analytic conditions are derived for
      community persistence, and the self-thinning exponent is obtained as a function
      of species characteristics and environmental conditions.

PMID- 15868196
TI  - Stability analysis of pathogen-immune interaction dynamics.
AB  - The paper considers models of dynamics of infectious disease in vivo from the
      standpoint of the mathematical analysis of stability. The models describe the
      interaction of the target cells, the pathogens, and the humoral immune response.
      The paper mainly focuses on the interior equilibrium, whose components are all
      positive. If the model ignores the absorption of the pathogens due to infection,
      the interior equilibrium is always asymptotically stable. On the other hand, if
      the model does consider it, the interior equilibrium can be unstable and a simple
      Hopf bifurcation can occur. A sufficient condition that the interior equilibrium
      is asymptotically stable is obtained. The condition explains that the interior
      equilibrium is asymptotically stable when experimental parameter values are used
      for the model. Moreover, the paper considers the models in which uninfected cells
      are involved in the immune response to pathogens, and are removed by the immune
      complexes. The effect of the involvement strongly affects the stability of the
      interior equilibria. The results are shown with the aid of symbolic calculation
      software.

PMID- 15868198
TI  - An analysis of vegetation stripe formation in semi-arid landscapes.
AB  - Vegetation stripes ("tiger bush") are a characteristic feature of semi-arid
      environments. The stripes typically lie along the contours of gentle slopes, and
      some authors report a gradual uphill migration. A previous mathematical model
      (Klausmeier, Science, 284:1826, 1999) has shown that this phenomenon can be
      explained relatively simply by the downhill flow of rainwater coupled with the
      diffusive spread of the plant population. This paper presents a detailed analysis
      of pattern formation in the Klausmeier model. The author derives formulae for the
      wavelength and migration speed of the predicted patterns, and systematically
      investigates how these depend on model parameters. The results make new
      predictions and suggest possible approaches to testing the model.

PMID- 15868197
TI  - Strand separation in negatively supercoiled DNA.
AB  - We consider Benham's model for strand separation in negatively supercoiled
      circular DNA, and study denaturation as function of the linking difference
      density kappa<0. We propose a statistical version of this model, based on
      bayesian segmentation methods of current use in bioinformatics; this leads to new
      algorithms with priors adapted to supercoiled DNA, taking into account the random
      nature of the free energies needed to denature base pairs.

PMID- 15868199
TI  - Lattice-Boltzmann model for bacterial chemotaxis.
AB  - We present a new numerical approach for modeling bacterial chemotaxis and the
      fate and transport of a chemoattractant in bulk liquids. This Lattice-Boltzmann
      method represents the microorganisms and the chemoattractant by quasi-particles
      that move, collide, and react with each other on a two-dimensional numerical
      lattice. We use the model to simulate traveling bands of bacteria along self
      generated gradients in substrate concentration in bulk liquids. Particularly, we
      simulate Pseudomonas putida that respond chemotactically to naphthalene dissolved
      in water. We find that only a fraction of a bacterial slug injected into a domain
      containing the chemoattractant at constant concentration forms a traveling band
      as the slug length exceeds a critical value. An expanding bacterial ring forms as
      one injects a droplet of bacteria into a two-dimensional domain.

PMID- 15868200
TI  - Calculating spatial statistics for velocity jump processes with experimentally
      observed reorientation parameters.
AB  - Mathematical modelling of the directed movement of animals, microorganisms and
      cells is of great relevance in the fields of biology and medicine. Simple
      diffusive models of movement assume a random walk in the position, while more
      realistic models include the direction of movement by assuming a random walk in
      the velocity. These velocity jump processes, although more realistic, are much
      harder to analyse and an equation that describes the underlying spatial
      distribution only exists in one dimension. In this communication we set up a
      realistic reorientation model in two dimensions, where the mean turning angle is
      dependent on the previous direction of movement and bias is implicitly introduced
      in the probability distribution for the direction of movement. This model, and
      the associated reorientation parameters, is based on data from experiments on
      swimming microorganisms. Assuming a transport equation to describe the motion of
      a population of random walkers using a velocity jump process, together with this
      realistic reorientation model, we use a moment closure method to derive and solve
      a system of equations for the spatial statistics. These asymptotic equations are
      a very good match to simulated random walks for realistic parameter values.

PMID- 15868201
TI  - Bounding the number of hybridisation events for a consistent evolutionary
      history.
AB  - Evolutionary processes such as hybridisation, lateral gene transfer, and
      recombination are all key factors in shaping the structure of genes and genomes.
      However, since such processes are not always best represented by trees, there is
      now considerable interest in using more general networks instead. For example, in
      recent studies it has been shown that networks can be used to provide lower
      bounds on the number of recombination events and also for the number of lateral
      gene transfers that took place in the evolutionary history of a set of molecular
      sequences. In this paper we describe the theoretical performance of some related
      bounds that result when merging pairs of trees into networks.

PMID- 15868202
TI  - Analysis and visualization of growth-related and treatment-induced craniofacial
      changes.
AB  - An analysis and visualization of craniofacial shape changes due to growth or
      orthodontic treatment is presented. The suggested method is based on an adapted
      Karhunen-Loeve decomposition of time-discrete data based on landmarks in lateral
      X-rays of the skull. It allows for a reduction of the high-dimensional dynamic
      problem to a few spatial modes representing synchronous components of growth
      patterns with time-dependent mode coefficients. The growth-related shape changes
      as well as the orthodontic treatment effects are visualized by overdrawing the
      underlying shape changes. The results based on this technique give insight into
      the still controversially discussed question to which degree the craniofacial
      skeletal structures can be influenced by orthodontic appliances.

PMID- 15868203
TI  - Analysis of the periodically fragmented environment model: I--species
      persistence.
AB  - This paper is concerned with the study of the stationary solutions of the
      equation [Equation: see text] where the diffusion matrix A and the reaction term
      f are periodic in x. We prove existence and uniqueness results for the stationary
      equation and we then analyze the behaviour of the solutions of the evolution
      equation for large times. These results are expressed by a condition on the sign
      of the first eigenvalue of the associated linearized problem with periodicity
      condition. We explain the biological motivation and we also interpret the results
      in terms of species persistence in periodic environment. The effects of various
      aspects of heterogeneities, such as environmental fragmentation are also
      discussed.

PMID- 15868207
TI  - Does 2,3-butanedione monoxime inhibit nonmuscle myosin?
AB  - BDM (2,3-butanedione monoxime) has been used extensively to inhibit nonmuscle
      myosin. However, recent articles raise the question of what BDM actually does,
      because of experiments in which BDM did not affect the actin-activated ATPase of
      nonmuscle myosins. We describe results that indicate that BDM indeed inhibits
      motility due to nonmuscle myosins: in many different cells BDM has the same
      effects as anti-actin agents and/or as other anti-myosin agents, and BDM slows or
      stops the sliding between actin filaments and myosin in vitro. We discuss how the
      two sets of apparently contradictory results might be resolved, and we suggest
      possible experiments that might clarify the contradictory interpretations.

PMID- 15868204
TI  - Alternative splicing removes an Ets interaction domain from Lozenge during
      Drosophila eye development.
AB  - Physical and functional characteristics of the RUNX family of transcription
      factors are conserved between vertebrates and the Drosophila protein Lozenge. The
      runt-homology domain responsible for DNA binding and also the C-terminus are both
      nearly identical between the two proteins. The mammalian and fly proteins
      heterodimerize with a non-DNA binding partner protein to form a core binding
      factor essential for gene regulation during cell differentiation. The mammalian
      protein RUNX1 (AML1/PEBP2alphaB) interacts with the transcription factor Ets-1 to
      increase DNA binding and transactivation potential. Alternative splicing of the
      mammalian RUNX1 removes a domain required for this cooperative transactivation.
      In this work we determine the structure of the lozenge transcription unit and map
      21 mutations. We show that the lozenge transcript is alternatively spliced during
      eye development to remove an Ets interaction domain. Emphasis is placed on
      Pointed the Drosophila homolog of the vertebrate Ets-1 protein; both Lozenge and
      Pointed proteins are needed for the activation of prospero expression. We use
      site-directed mutagenesis and yeast two-hybrid analysis to show that conserved
      amino acids within the alternate Lozenge exon are important for interaction with
      Pointed. Furthermore, the ectopic expression of Lozenge is sufficient to rescue
      Prospero expression in the presence of the Pointed competitor, Yan(ACT). We show
      that both lozenge isoforms are expressed during eye development and that the
      relative ratio of the transcripts for the two isoforms is sensitive to changes in
      Ras activity. We suggest that during eye development, Lozenge isoforms function
      in divergent roles, either interacting with Pointed on downstream targets or by
      functioning independently to establish distinct cell fates.

PMID- 15868205
TI  - [Psychiatric epidemiology and public health medicine. Principles of health
      service research].
AB  - Psychiatric illnesses are among the most common diseases in the general
      population and contribute significantly to the global disease burden. Psychiatric
      epidemiology yields scientific estimations of the incidence and prevalence of
      psychiatric diseases and their associated risk factors. It has also been found
      that treatment needs are determined by several factors. Health service research
      analyses treatment needs and whether they are met. The analysis of direct and
      indirect health care costs and effectiveness are gaining importance in mental
      health service research.

PMID- 15868208
TI  - Paternal cytoplasmic transmission in Chinese pine (Pinus tabulaeformis).
AB  - In this paper, the stages of normal sexual reproduction between pollen tube
      penetration of the archegonium and early embryo formation in Pinus tabulaeformis
      are described, emphasizing the transmission of parental cytoplasm, especially the
      DNA-containing organelles--plastids and mitochondria. The pollen tube growing in
      the nucellus contained an irregular tube nucleus followed by a pair of sperm
      cells. The tube cytoplasm contained abundant organelles, including starch
      containing plastids and mitochondria. The two sperm cells differed in their
      volume of cytoplasm. The leading sperm, with more cytoplasm, contained abundant
      plastids and mitochondria, while the trailing one, with a thin layer of
      cytoplasm, had very few organelles. The mature egg cell contained a great number
      of mitochondria, whereas it lacked normal plastids. At fertilization, the pollen
      tube penetrated into the egg cell at the micropylar end and released all of its
      contents, including the two sperms. One of the sperm nuclei fused with the egg
      nucleus, whereas the other one was retained by the receptive vacuole. Very few
      plastids and mitochondria of male origin were observed around the fusing sperm
      and egg nuclei, while the retained sperm nucleus was surrounded by a large amount
      of male cytoplasm. The discharged tube cytoplasm occupied a large micropylar area
      in the egg cell. In the free nuclear proembryo, organelles of maternal and
      paternal origins intermingled in the neocytoplasm around the free nuclei. Most of
      the mitochondria had the same features as those of the egg cell, but some
      appeared to be from sperm cells and tube cytoplasm. Plastids were obviously of
      male origin, with an appearance similar to those of the sperm or tube cells.
      After cellularization of the proembryo, maternal mitochondria became more
      abundant than the paternal ones and the plastids enlarged and began to accumulate
      starch. The results reveal the cytological mechanism for paternal inheritance of
      plastids and biparental inheritance of mitochondria in Chinese pine.

PMID- 15868209
TI  - Immunocytochemistry of pectins in shoot apical meristems: consequences for
      intercellular adhesion.
AB  - The nature of pectins (acidic, methyl-, or acetyl-esterified) in the shoot
      meristem of Sinapis alba was assessed by immunocytochemistry with the 2F4
      monoclonal antibody in light and electron microscopy. This antibody is specific
      for "egg-boxes"--the polygalacturonic acid conformation induced by calcium as
      described in Liners et al. (Plant Physiol. 99: 1099-1104, 1992). Hardly any
      acidic pectin was detected in meristem walls; the pectins were largely methyl
      esterified and esterified by acetyl groups and/or other esters. After in situ
      chemical or enzymatic de-esterification, labeling was distributed over the
      primary wall and the middle lamella of meristematic cells. Acidic pectin and Ca2+
      cross-linked homogalacturonans were absent from the pit fields, where
      plasmodesmata traverse the middle lamella. The type and distribution of pectins
      are discussed in relation to cellular adhesion between active meristem cells.

PMID- 15868210
TI  - Live-cell imaging of tubulin in the filamentous fungus Magnaporthe grisea treated
      with anti-microtubule and anti-microfilament agents.
AB  - Microtubule dynamics were examined in live cells of the fungal plant pathogen
      Magnaporthe grisea transformed for constitutive expression of a fusion protein
      containing enhanced yellow-fluorescent protein and a Neurospora crassa benomyl
      resistant allele of beta-tubulin. Transformants retained their ability to
      differentiate appressoria and cause disease but remained sensitive to benomyl.
      Linear microtubule arrays and low-level cytoplasmic fluorescence were observed in
      vegetative hyphae, conidia, germ tubes, and developing appressoria. Fluorescence
      within nuclei was conspicuously absent during interphase but increased rapidly at
      the onset of mitosis. Treatment with either benomyl or griseofulvin resulted in
      the appearance of prominent brightly fluorescent aggregates, including a large
      aggregate near the apex, with the concomitant disappearance of most cytoplasmic
      microtubules. Electron microscope imaging of treated cells indicated that the
      aggregates lacked any obvious profiles of intact microtubules. During these
      treatments, hyphal tip cells continued to elongate in a nonlinear and aerial
      fashion at a much slower rate than untreated cells. With subsequent removal of
      griseofulvin, distal aggregates disappeared rapidly but the apical aggregates
      persisted longer. Treatment with latrunculin A caused hyphal tip swelling without
      apparent effect on linear microtubule arrays. Simultaneous treatment with
      griseofulvin and latrunculin A resulted in depolymerization of microtubules and a
      cessation of growth, but near-apical fluorescent aggregates were not observed.

PMID- 15868211
TI  - Plastid stromules: video microscopy of their outgrowth, retraction, tensioning,
      anchoring, branching, bridging, and tip-shedding.
AB  - Stromules are stroma-containing tubules which can grow from the surface of
      plastids, most commonly leucoplasts and chromoplasts, but also chloroplasts in
      some tissues. Their functions are obscure. Stills from video rate movies are
      presented here. They illustrate interaction of stromules with cytoskeletal
      strands and the anchoring of stromules to unidentified components at the cell
      surface. Anchoring leads to stretching and relaxation of stromules when forces
      arising from cytoplasmic streaming act on the attached, freely suspended plastid
      bodies. Data on stromule growth, retraction, and regrowth rates are provided.
      Formation and movement of stromular branches and bridges between plastids are
      described. The shedding of a tip region into the streaming cytoplasm is recorded
      in frame-by-frame detail, in accord with early observations.

PMID- 15868212
TI  - Accumulation of extracellular proteins bearing unique proline-rich motifs in
      intercellular spaces of the legume nodule parenchyma.
AB  - Nodulins encoding repetitive proline-rich cell wall proteins (PRPs) are induced
      during early interactions with rhizobia, suggesting a massive restructuring of
      the plant extracellular matrix during infection and nodulation. However, the
      proteins corresponding to these gene products have not been isolated or
      characterized, nor have cell wall localizations been confirmed. Posttranslational
      modifications, conformation, and interactions with other wall polymers are
      difficult to predict on the basis of only the deduced amino acid sequence of
      PRPs. PsENOD2 is expressed in nodule parenchyma tissue during nodule
      organogenesis and encodes a protein with distinctive PRP motifs that are rich in
      glutamate and basic amino acids. A database search for the ENOD2 signature motifs
      indicates that similar proteins may have a limited phylogenetic distribution, as
      they are presently only known from legumes. To determine the ultrastructural
      location of the proteins, antibodies were raised against unique motifs from the
      predicted ENOD2 sequence. The antibodies recognized nodule-specific proteins in
      pea (Pisum sativum), with a major band detected at 110 kDa, representing a subset
      of PRPs from nodules. The protein was detected specifically in organelles of the
      secretory pathway and intercellular spaces in the nodule parenchyma, but it was
      not abundant in primary walls. Similar proteins with an analogous distribution
      were detected in soybean (Glycine max). The use of polyclonal antibodies raised
      against signature motifs of extracellular matrix proteins thus appears to be an
      effective strategy to identify and isolate specific structural proteins for
      functional analysis.

PMID- 15868213
TI  - Chemical characterization and antifungal activity of essential oil of capitula
      from wild Indian Tagetes patula L.
AB  - The essential oil extracted by steam distillation from the capitula of Indian
      Tagetes patula, Asteraceae, was evaluated for its antifungal properties and
      analyzed by gas chromatography and gas chromatography-mass spectrometry. Thirty
      compounds were identified, representing 89.1% of the total detected. The main
      components were piperitone (24.74%), piperitenone (22.93%), terpinolene (7.8%),
      dihydro tagetone (4.91%), cis-tagetone (4.62%), limonene (4.52%), and allo
      ocimene (3.66%). The oil exerted a good antifungal activity against two
      phytopathogenic fungi, Botrytis cinerea and Penicillium digitatum, providing
      complete growth inhibition at 10 microl/ml and 1.25 microl/ml, respectively. The
      contribution of the two main compounds, piperitone and piperitenone, to the
      antifungal efficacy was also evaluated and ultrastructural modifications in
      mycelia were observed via electron microscopy, evidencing large alterations in
      hyphal morphology and a multisite mechanism of action.

PMID- 15868214
TI  - Development of a quantitative tool for measuring changes in the coefficient of
      conductivity of plasmodesmata induced by developmental, biotic, and abiotic
      signals.
AB  - The regulation of intercellular and interorgan communication is pivotal for cell
      fate decisions in plant development and probably plays a significant role in the
      systemic regulation of gene expression and in defense reactions against pathogens
      or other biotic and abiotic environmental factors. In plants, symplasmic cell-to
      cell communication is provided by plasmodesmata (Pd), coaxial membranous tunnels
      that span cell walls interconnecting adjacent cytoplasms. Macromolecules,
      proteins, and RNA may be transported through Pd by passive diffusion or by a
      facilitated mechanism. A quantitative tool was developed to measure the
      coefficient of conductivity, C(Pd), for diffusion-driven transport via Pd and to
      assess changes in the coefficient induced by developmental, biotic and abiotic
      signals. (GFP)C(Pd), the coefficient of conductivity for cell-to-cell spread of
      green-fluorescent protein (GFP), a protein with a Stokes radius of 2.82 nm, was
      determined in epidermal cells of sink and source leaves of wild-type and
      transgenic Nicotiana benthamiana plants expressing the movement protein of
      tobacco mosaic virus (MP(TMV)) incubated both in dark and light and at 16 and 25
      degrees C. Under all conditions, Pd in source leaves conducted macromolecules,
      with (GFP)C(Pd)sink>(GFP)C(Pd)source. Light down-regulated (GFP)C(Pd) (all
      conditions); down-regulation was stronger for sink cells. The effect of MP(TMV)
      on (GFP)C(Pd) between epidermal cells was dependent on temperature and leaf
      development; at 16 degrees C, MP(TMV) down-regulated (GFP)C(Pd) only in source
      leaves, while at 25 degrees C, MP(TMV) had no significant effect. This
      quantitative tool should be useful for investigating differences in Pd
      conductivity that are induced by mutations or silencing.

PMID- 15868215
TI  - An extraction method for tobacco mosaic virus movement protein localizing in
      plasmodesmata.
AB  - The intercellular communication by plasmodesmata (PD) is important for the growth
      and development of plants, and the transport of macromolecules through PD is
      likely to be regulated by developmental signals. While PD in the apical meristem
      transport macromolecules such as mRNAs, the branched PD in the mature leaf do not
      transport large macromolecules freely. The changes in PD during development might
      be important for sink-to-source changes in leaves, but the molecular mechanism is
      still unknown. Movement proteins (MPs) of the tobacco mosaic virus localize in
      the branched PD and increase the size exclusion limit, allowing transport of
      viral RNA. We developed a method for differential extraction of MP from isolated
      cell walls of transgenic tobacco leaves expressing MP or MP tagged with green
      fluorescent protein. Lithium chloride at a concentration of 8 M removed
      filamentous structures in branched PD, the possible attachment site of MP. As
      some endogenous proteins were coeluted with MP by the treatment, this extraction
      method might be a powerful tool for investigating MP-interacting proteins in
      branched PD.

PMID- 15868216
TI  - Spirostomum spp. (Ciliophora, Protista), a suitable system for endocytobiosis
      research.
AB  - Among ciliate genera, only Paramecium and Euplotes species have been studied
      extensively as host organisms of bacterial endocytobionts. In this article, we
      show that members of the genus Spirostomum may also serve as a suitable system
      for endocytobiosis research. Two strains of Spirostomum minus (Heterotrichea,
      Ciliophora) collected in Germany and Italy, respectively, were found to harbor
      different types of bacterial infections. Bacteria of various sizes and shapes
      were observed in the cytoplasm or in the nuclei of the ciliates. The bacteria in
      the cytoplasm were either surrounded by a peribacterial membrane or lay naked.
      One of the bacterial species was found in the vicinity of the contractile
      fibrillar system (myonemes) of the ciliates. In rare cases, another type of
      bacteria was observed associated with mitochondria. The macronuclei of both the
      Italian and the German strains were crowded with endocytobionts. The endonuclear
      bacteria in the two S. minus strains differed with respect to their cytoplasmic
      structures but they were of similar size and both were rod shaped. According to
      the results of in situ hybridization, the endonuclear bacteria of the Italian
      strain belong to the subgroup of alphaproteobacteria, whereas the bacteria
      associated with the fibrillar system appeared to be gram-positive bacteria with
      high G+C content. While both the German and the Italian strains were found to
      permanently maintain their endocytobionts, they were at least partly colonized by
      different bacteria. This is taken as an indication that geographically separated
      populations of ciliates may be stably infected by different endocytobionts,
      possibly due to different ecological conditions. For S. minus and S. ambiguum a
      total of 7 different bacterial endocytobionts have now been recorded. We
      recommend the members of the genus Spirostomum as a suitable system for
      endocytobiosis research.

PMID- 15868217
TI  - Calcium changes and the response to methyl jasmonate in rice lodicules during
      anthesis.
AB  - Potassium pyroantimonate precipitation was used to locate loosely bound calcium
      in rice (Oryza sativa L.) lodicules before and after anthesis, and flowering of
      panicles was accelerated by treatment with methyl jasmonate. From 1 day to 4 h
      before anthesis, the number of calcium precipitates in the cell walls and vacuole
      membranes decreased gradually, whereas they increased remarkably in the cytoplasm
      and nucleolus. At the beginning of anthesis, the number of calcium granules in
      lodicules reduced sharply, but there was a large accumulation of flocculent
      precipitates in the vacuoles. After anthesis, the flocculent precipitates
      decreased in number until they disappeared, whereas the granular precipitates
      started to accumulate once again. The rice florets treated with 2 mM methyl
      jasmonate were induced to open within 10-30 min and they then closed 0.5-1 h
      later. The nucleolus, cytoplasm, and vacuole membrane of the lodicule cells
      contained many calcium granules during flowering, although the cell walls lacked
      calcium. At 1 h after treatment, the number of calcium granules had decreased,
      while flocculent precipitates were regularly observed in the nondegenerated
      cells. At 6 h after treatment, calcium grains started to reappear in the cell
      walls. These changes in calcium precipitates before and after anthesis indicate
      that the opening and closing of florets correlates with the calcium level in
      lodicule cells. In addition, excised panicles, with florets judged to be nearing
      anthesis, were soaked in 2-200 mM EGTA solution for 2 min after treatment with 2
      mM methyl jasmonate. The results indicate that EGTA had an antagonistic effect on
      the methyl jasmonate-induced floret opening in rice.

PMID- 15868218
TI  - Localization of myosin II to chromosome arms and spindle fibers in PtK1 cells: a
      possible role for an actomyosin system in mitosis.
AB  - The enzymes of importance in moving chromosomes are called motor proteins and
      include dynein, kinesin, and possibly myosin II. These three molecules are all
      included in the category of ATPases, in that they have the ability to convert
      chemical energy into mechanical energy. Both dynein and kinesin have been
      documented as molecules that "walk" along microtubules in the mitotic spindle,
      carrying cargo such as chromosomes. Myosin II, analogous to the muscle
      contraction system, transiently interacts along actin filaments and associates
      with kinetochore microtubules. In this paper we present evidence that a third
      ATPase, myosin II, may act as a "thruster" to propel chromosomes during the
      mitotic process. Double-label immunocytochemistry to actin and myosin II shows
      that myosin II is localized on chromosome arms at the beginning of mitosis and
      remains localized to the chromosomes throughout mitosis. Specific staining of
      myosin II is relegated to the outside of chromosomes with the highest density of
      staining occurring between the spindle poles and the chromosomes. This specific
      localization could account for the movement of chromosomes during mitosis, since
      they segregate towards the spindle poles, along kinetochore microtubules
      containing actin filaments, after aligning at the equatorial region of the cell
      at metaphase. We conclude from this study that there is an actomyosin system
      present in the mitotic spindle and that myosin is attached to chromosome arms and
      may act as a thruster in moving chromosomes during the mitotic process.

PMID- 15868219
TI  - Localization of specific monosaccharides in cells of the brown alga Padina
      gymnospora and the relation to heavy-metal accumulation.
AB  - The brown alga Padina gymnospora has been studied due to their ecological
      significance and biochemical characteristics, including its high capability of
      heavy-metal accumulation. It has been suggested that the fucans are among the
      main polysaccharides related to metal binding and precipitation in cell walls.
      The main purpose of this work was to determine the localization of specific
      monosaccharides in P. gymnospora cells. In this way, the lectins Ulex europaeus
      agglutinin and Canavalia ensiformis concanavalin A with specificity to alpha-L
      fucose and to terminal residues of alpha-D-glucosyl and alpha-D-mannosyl,
      respectively, were applied in young individuals. These revealed a preferential
      distribution of alpha-L-fucose at cell walls near the external surface in
      cortical cells and near the plasmalemma in cortical and medullar cells. The
      distribution of alpha-L-fucose in cell walls indicates the distribution of
      sulfated polysaccharides (sulfated fucans) that colocalize with the heavy-metal
      granules (Zn and Cd) described in previous works. Therefore, our results suggest
      that alpha-L-fucose participates in the nucleation and immobilization of heavy
      metals in P. gymnospora cell walls. An intense labeling of U. europaeus
      agglutinin and a weak labeling of concanavalin A was also observed in physodes. X
      ray microanalysis revealed the presence of zinc, sulfur, and calcium in physodes
      of algae collected in a heavy-metal-contaminated area. Besides the affinity
      between polyphenolic compounds and heavy metals, it is suggested that the
      mechanism of metal binding by physodes could be related to the presence of
      sulfated fucans.

PMID- 15868220
TI  - Functional and anatomic outcome after transvaginal rectocele repair using
      collagen mesh: a prospective study.
AB  - PURPOSE: This study was designed to evaluate rectocele repair using collagen
      mesh. METHODS: 32 female patients underwent surgical repair using collagen mesh.
      Outcome was assessed in 29 patients and preoperative assessment included
      standardized questionnaire, clinical examination, and defecography. At the six
      month follow-up, patients answered a standardized questionnaire and underwent
      clinical examination. At the 12-month follow-up, patients answered a standardized
      questionnaire, underwent clinical examination, and defecography. RESULTS:
      Preoperatively, 26 patients had a Stage II and 3 patients had a Stage III
      rectocele. At the 6-month follow-up, five patients had rectocele > or = Stage II
      (P < 0.001) and at the 12-month follow-up, seven patients had rectocele > or =
      Stage II (P < 0.001) at clinical examination. At the preoperative defecography,
      all patients presented a rectocele. At the 12-month defecography, 14 patients had
      no rectocele (P < 0.001) and 15 had a rectocele. At the six-month follow-up,
      there was a significant decrease in rectal emptying difficulties, need of digital
      support of the posterior vaginal wall at defecation, and defecation frequency. At
      the 12-month follow-up, symptom improvement remained, but was less pronounced.
      CONCLUSIONS: Rectocele repair using collagen mesh improved anatomic support, but
      there is a substantial risk for recurrence with unsatisfactory anatomic and
      functional outcome one year after surgery. Rectocele repair using mesh was not
      associated with an increased risk of dyspareunia. Rectocele repair using
      biomaterial mesh reinforcement needs further evaluation before adopted into
      clinical practice.

PMID- 15868221
TI  - Use of CT colonography in low-risk populations.

PMID- 15868223
TI  - Stapled hemorrhoidopexy.

PMID- 15868224
TI  - The value of plasma cytokine measurement for the detection of strangulation in
      patients with bowel obstruction: a prospective, pilot study.
AB  - PURPOSE: The aim of this prospective blinded study was to examine whether
      measurement of plasma cytokines is a predictor of strangulation in patients with
      bowel obstruction. METHODS: Seventy-seven consecutive patients diagnosed with
      bowel obstruction were included. Blood samples were obtained at enrollment in all
      patients and at surgery (immediately before operation) if patients required
      surgery. RESULTS: Forty-three patients were managed conservatively (group 1) and
      34 patients required surgery, of whom 20 had no bowel strangulation (group 2) and
      14 had bowel strangulation (group 3). The mean plasma interleukin (IL)-6 levels
      at enrollment were significantly higher in group 3 (107.8 pg/ml) than in groups 1
      (11.3 pg/ml, P < 0.0001 vs. group 3) and 2 (23.6 pg/ml, P < 0.0001 vs. group 3).
      The sensitivity and specificity of plasma IL-6 level (> or = 40 pg/ml) in
      predicting strangulation were 86 percent (95 percent confidence interval, 60-97
      percent) and 86 percent (95 percent confidence interval, 80-88 percent),
      respectively. The plasma IL-6 levels at surgery significantly increased compared
      to those at enrollment (from 107.8 pg/ml to 205.8 pg/ml, P = 0.0003) in group 3,
      however, they did not increase significantly in group 2. Among other clinical and
      laboratory parameters, plasma lactic acid levels (> or = 15 mg/dl) at enrollment
      were significantly associated with strangulation. In the multivariate analysis,
      both plasma IL-6 (</> or = 40 pg/ml) and lactic acid (</> or =15 mg/dl) levels at
      enrollment were significant predictive factors for strangulation. IL-1beta and
      tumor necrosis factor-alpha were not detected in the plasma of most patients
      during the study. CONCLUSION: Plasma IL-6 measurement might be an additional
      diagnostic tool that can predict strangulation in patients with bowel
      obstruction.

PMID- 15868225
TI  - Anal stenosis after LigaSure hemorrhoidectomy.

PMID- 15868226
TI  - The role of arachidonic acid regulatory enzymes in colorectal disease.
AB  - PURPOSE: Nonsteroidal anti-inflammatory drugs have a wide ranging effect on
      diseases of the colon and rectum. Interestingly, nonsteroidal anti-inflammatory
      drugs seem to play a beneficial role in colorectal cancer chemoprevention and
      adenoma regression, but may have a deleterious effect in inflammatory bowel
      disease. Prostaglandin inhibition is central to both the beneficial and toxic
      effects of this class of drugs. Arachidonic acid metabolism is essential to
      prostaglandin synthesis. METHODS: A Medline search using "nonsteroidal anti
      inflammatory drugs," "colon cancer," "inflammatory bowel disease," "colitis,"
      "COX inhibitors," "arachidonic acid," and "chemoprevention" as key words was
      performed for English-language articles. Further references were obtained through
      cross-referencing the bibliography cited in each work. RESULTS: Based on numerous
      studies, nonsteroidal anti-inflammatory drugs have a beneficial role in colon
      cancer and colonic adenomas. However, they have been reported to have a
      deleterious effect on the colon in inflammatory bowel disease and have been shown
      to cause colitis. Nonsteroidal anti-inflammatory drugs work via multiple
      pathways, some well defined, and others unknown. CONCLUSIONS: In the new
      millennium, nonsteroidal anti-inflammatory drugs may be used for chemoprevention
      of colorectal and other cancers. In addition, they may be used in combination
      with surgery and chemotherapy to primarily treat colorectal carcinoma.
      Undoubtedly, the use of novel cyclooxygenase inhibitors with less of a toxicity
      profile will allow more widespread use of nonsteroidal anti-inflammatory drugs
      for a variety of diseases. The future of this class of drugs is promising.

PMID- 15868228
TI  - Serologic responses in indeterminate colitis patients before ileal pouch-anal
      anastomosis may determine those at risk for continuous pouch inflammation.
AB  - PURPOSE: Although acute pouchitis after ileal pouch-anal anastomosis is common
      and easily treated, continuous pouch inflammation seen clinically as chronic,
      antibiotic-dependent pouchitis, and/or Crohn's disease remains a difficult
      management problem. Compared with ulcerative colitis, indeterminate colitis
      patients undergoing ileal pouch-anal anastomosis have a higher incidence of
      continuous pouch inflammation, which may represent persistent immune reactivity
      to microbial antigens. Antibody responses to three microbial antigens
      (oligomannan anti-Saccharomyces cerevisiae, outer membrane porin C of Escherichia
      coli, and an antigen (I2) from Pseudomonas flourescens) are more commonly seen in
      Crohn's disease, whereas antibodies to a cross-reactive antigen (perinuclear
      antineutrophil cytoplasmic antibodies) is more suggestive of ulcerative colitis.
      We examined whether preoperative serologic responses to these antigens were
      associated with Crohn's disease in indeterminate colitis patients after ileal
      pouch-anal anastomosis. METHODS: Twenty-eight indeterminate colitis patients
      undergoing ileal pouch-anal anastomosis were prospectively assessed for the
      development of pouchitis or Crohn's disease. Serologic responses were determined
      by enzyme-linked immunosorbent assay and immunofluorescence. Patients were
      classified based on four predominant profiles of antibody expression. Antibody
      profiles were determined before knowledge of clinical outcome. RESULTS: Median
      follow-up was 38 (range, 3-75) months. Of 16 patients (61 percent) who developed
      pouch inflammation, 4 (25 percent) had acute pouchitis and 12 (75 percent) had
      continuous pouch inflammation (9 had chronic pouchitis, 3 had Crohn's disease).
      No preoperative clinical factor predicted the development of these pouch
      complications. Overall, 16 patients (57 percent) had a positive antibody
      reactivity profile. Serologic expression of any marker alone did not predict the
      development of continuous pouch inflammation. However, continuous pouch
      inflammation developed in 10 of 16 patients (63 percent) who had a positive
      antibody reactivity profile compared with only 2 of 12 patients (17 percent) who
      had a negative antibody reactivity profile (P = 0.015). CONCLUSIONS:
      Indeterminate colitis patients who have a positive antibody reactivity profile
      before ileal pouch-anal anastomosis have a significantly higher incidence of
      continuous pouch inflammation after surgery than those with a negative profile.

PMID- 15868230
TI  - Prevention of postoperative abdominal adhesions by a novel, glycerol/sodium
      hyaluronate/carboxymethylcellulose-based bioresorbable membrane: a prospective,
      randomized, evaluator-blinded multicenter study.
AB  - INTRODUCTION: Postoperative abdominal adhesions are associated with significant
      morbidity and mortality, placing a substantial burden on healthcare systems
      worldwide. Development of a bioresorbable membrane containing up to 23 percent
      glycerol and chemically modified sodium hyaluronate/carboxymethylcellulose offers
      ease of handling and has been shown to provide significant postoperative adhesion
      prevention in animals. This study was designed to assess the safety of glycerol
      hyaluronate/carboxymethylcellulose and to evaluate its efficacy in reducing the
      incidence, extent, and severity of postoperative adhesion development in surgical
      patients. METHODS: Twelve centers enrolled 120 patients with ulcerative colitis
      or familial polyposis who were scheduled for a restorative proctocolectomy and
      ileal pouch-anal anastomosis with diverting loop ileostomy. Before surgical
      closure, patients were randomized to no anti-adhesion treatment (control) or
      treatment with glycerol hyaluronate/carboxymethylcellulose membrane under the
      midline incision. At ileostomy closure, laparoscopy was used to evaluate the
      incidence, extent, and severity of adhesion formation to the midline incision.
      RESULTS: Data were analyzed using the intent-to-treat population. Treatment with
      glycerol hyaluronate/carboxymethylcellulose resulted in 19 of 58 patients (33
      percent) with no adhesions compared with 6 of 60 adhesion-free patients (10
      percent) in the no treatment control group (P = 0.002). The mean extent of
      postoperative adhesions to the midline incision was significantly lower among
      patients treated with glycerol hyaluronate/carboxymethylcellulose compared with
      patients in the control group (P < 0.001). The severity of postoperative
      adhesions to the midline incision was significantly less with glycerol
      hyaluronate/carboxymethylcellulose than with control (P < 0.001). Adverse events
      were similar between treatment and no treatment control groups with the exception
      of abscess and incisional wound complications were more frequently observed with
      glycerol hyaluronate/carboxymethylcellulose. CONCLUSIONS: Glycerol
      hyaluronate/carboxymethylcellulose was shown to effectively reduce adhesions to
      the midline incision and adhesions between the omentum and small bowel after
      abdominal surgery. Safety profiles for the treatment and no treatment control
      groups were similar with the exception of more infection complications associated
      with glycerol hyaluronate/carboxymethylcellulose use. Animal models did not
      predict these complications.

PMID- 15868232
TI  - The quality of podium presentations at the american society of colon and rectal
      surgeons: does a decade make a difference?
AB  - PURPOSE: The technology of the seven-minute scientific presentation has changed
      greatly with the universal acceptance of computerized slides and graphics. We
      performed this study to see whether the quality of delivery has improved pari
      passu with technical advances in presentation of data. METHODS: In 1993 and in
      2003 a sample of the podium presentations given at The American Society of Colon
      and Rectal Surgeons annual scientific meeting was analyzed. Number of slides,
      type of slides, time of presentation, and quality of presentation were recorded.
      Quality was scored by the presence of poor presentation techniques such as
      presenting too fast for the slide to be comprehended, presenting data that were
      different to what was on the slide, using fonts that were too small to be read,
      and reading the exact wording of the slide. One point was awarded for each
      transgression and for any talk lasting more than 7.9 minutes; the higher the
      score, the worse the presentation. RESULTS: Thirty-eight presentations were
      analyzed from the 1993 meeting in Orlando and 40 were analyzed from the 2003
      meeting in New Orleans. There was no difference in mean time of the presentation
      (1993, 7.5 minutes +/- 1.5 standard deviation vs. 2003, 7.2 minutes +/- 0.7
      standard deviation), in mean number of slides used per presentation (1993, 16.4
      +/- 3.3 standard deviation vs. 2003, 17.1 +/- 5.4 standard deviation), or in
      slides per minute (1993, 2.3 +/- 0.8 standard deviation vs. 2003, 2.5 +/- 1.0
      standard deviation). Presentation technique was much worse in 1993, however, with
      a mean quality score of 2.2 +/- 1.1 standard deviation vs. 0.8 +/- 0.9 standard
      deviation in 2003 (P < 0.001). The most common fault in both years was presenting
      a slide too rapidly, a fault more pervasive in 1993 than in 2003 (1993, 30/38
      presentations vs. 2003, 16/40). Only ten presentations went over the allotted
      time in 2003, by an average of one minute. In 1993, 18 presentations were too
      long, by an average of 1.8 minutes each. CONCLUSIONS: The basic structure of the
      seven-minute podium presentation has changed little over the last ten years,
      despite major advances in technology. The most notable improvements have been in
      the technique of delivering the talk.

PMID- 15868233
TI  - Management of peristomal pyoderma gangrenosum.
AB  - PURPOSE: This study was designed to evaluate the presentation, management, and
      outcome of peristomal pyoderma gangrenosum at a specialist colorectal unit and
      develop a strategy for therapy. METHODS: Patients with peristomal pyoderma
      gangrenosum were identified from a prospectively accrued Institutional Review
      Board-approved stoma database. Data were collected regarding demographics,
      disease status, history of illness, time to healing, and treatments used from the
      database and by chart review. RESULTS: Sixteen patients presented between 1997
      and 2002 with peristomal ulceration consistent with a diagnosis of peristomal
      pyoderma gangrenosum. Diagnosis was predominantly clinically based on a classic
      presentation of painful, undermined peristomal ulceration. The underlying
      diagnosis was Crohn's disease in 11 patients, ulcerative colitis in 3,
      indeterminate colitis in 1, and posterior urethral valves in 1. At the time of
      development of peristomal pyoderma gangrenosum, the underlying disease was active
      in 69 percent of patients. Stoma care, ulcer debridement with unroofing of
      undermined edges, and intralesional corticosteroid injection was associated with
      a 40 percent complete response rate and further 40 percent partial response rate.
      Of five patients who received infliximab, four (80 percent) responded to therapy.
      Complete response after all forms of therapy, including stoma relocation in seven
      patients, was 87 percent. CONCLUSIONS: Local wound management and enterostomal
      therapy are extremely important for patients with peristomal pyoderma
      gangrenosum. Infliximab may provide a useful option for those failing other forms
      of medical therapy. Relocation of the stoma is reserved for persistent ulceration
      failing other therapies, because peristomal pyoderma gangrenosum may recur at the
      new stoma site.

PMID- 15868234
TI  - Smoking impairs rectal mucosal bloodflow--a pilot study: possible implications
      for transanal advancement flap repair.
AB  - Transanal advancement flap repair has been advocated as the treatment of choice
      for trans-sphincteric perianal fistulas, because it enables the healing of almost
      all fistulas without sphincter damage and consequent continence disturbance.
      After initial promising reports, recently less favorable results have been
      reported. It remains unclear why there is such a large variety in the reported
      healing rates. Recently, it has been suggested that impaired wound healing caused
      by a diminished rectal mucosal perfusion in patients who smoke may lead to the
      breakdown of the advancement flap in patients undergoing flap repair for perianal
      fistulas. This study was designed to investigate the difference in blood flow in
      rectal mucosa between patients who smoke and those who do not smoke. Furthermore,
      we assessed the impact of the creation of a mucosa advancement flap and the
      difference in blood flow in the flap between smoking and nonsmoking patients.
      Between July 2001 and July 2002, 23 consecutive patients (19 males; median age,
      46 (range, 26-69) years) with a perianal fistula of cryptoglandular origin
      underwent surgery for a perianal fistula. Among them were 13 patients who smoked
      cigarettes. All patients underwent intraoperative laser Doppler flowmetry. Median
      blood flow before transanal advancement flap repair was 35 (range, 8-70) volts in
      patients who did not smoke. In patients who smoked the median blood flow before
      transanal advancement flap repair was 18 (range, 7-35) volts. Blood flow was
      significantly lower in patients who smoked (P = 0.018; Mann-Whitney). In
      conclusion, it seems likely that impaired wound healing caused by a diminished
      rectal mucosal perfusion is a contributing factor in the breakdown of advancement
      flaps in patients who smoke cigarettes.

PMID- 15868235
TI  - The development of a validated instrument to evaluate bowel function after
      sphincter-preserving surgery for rectal cancer.
AB  - PURPOSE: Sphincter-preserving surgery is technically feasible for many rectal
      cancers, but functional results are not well understood. Therefore, the purpose
      of this study was to develop an instrument to evaluate bowel function after
      sphincter-preserving surgery. METHODS: A 41-item bowel function survey was
      developed from a literature review, expert opinions, and 59 patient interviews.
      An additional 184 patients who underwent sphincter-preserving surgery between
      1997 and 2001 were asked to complete the survey and quality-of-life instruments
      (Fecal Incontinence Quality of Life, European Organization for Research and
      Treatment of Cancer QLQ 30/Colorectal Cancer 38). A factor analysis of variance
      was performed. Test-retest reliability was evaluated, with 20 patients completing
      two surveys within a mean of 11 days. Validity testing was done with clinical
      variables (gender, age, radiation, length of time from surgery), surgical
      variables (procedure: local excision, low anterior resection, coloanal
      anastomosis), reconstruction (J-pouch, straight), anastomosis (handsewn,
      stapled), and quality-of-life instruments. RESULTS: The survey response rate was
      70.1 percent (129/184). Among the 127 patients with usable data, 67 percent were
      male, the median age was 64 (range, 38-87) years, and the mean time for
      restoration of bowel continuity after sphincter-preserving surgery was 22.9
      months. Patients had a median of 3.5 stools/day (range, 0-30), and 37 percent
      were dissatisfied with their bowel function. Patients experienced a median of 22
      symptoms (range, 7-32), with 27 percent reported as severe, 37 percent as
      moderate, and 36 percent as mild. The five most common symptoms were incomplete
      evacuation (96.8 percent), clustering (94.4 percent), food affecting frequency
      (93.2 percent), unformed stool (92.8 percent), and gas incontinence (91.8
      percent). The factor analysis identified 14 items that collapsed into three
      subscales: FREQUENCY (alpha = 0.75), DIETARY (alpha = 0.78), and SOILAGE (alpha =
      0.79), with acceptable test-retest reliability for the three subscales and total
      score (0.62-0.87). The instrument detected differences between patients with
      preoperative radiation (n = 67) vs. postoperative radiation (n = 15) vs. no
      radiation (n = 45) (P = 0.02); local excision (n = 10) vs. low anterior resection
      (n = 55) vs. coloanal anastomosis (n = 62) (P = 0.002); and handsewn (n = 18) vs.
      stapled anastomosis (n = 99) (P = 0.006). The total score correlated with 4 of 4
      Fecal Incontinence Quality of Life (P < 0.01) and 9 of 17 European Organization
      for Research and Treatment of Cancer subscales (all P < 0.01). CONCLUSIONS:
      Patients undergoing sphincter-preserving surgery for rectal cancer have impaired
      bowel function, and those treated with radiation, coloanal anastomoses, or
      handsewn anastomoses have significantly worse function. This reliable and valid
      instrument should be used to prospectively evaluate bowel function after
      sphincter-preserving surgery in patients undergoing rectal cancer therapy.

PMID- 15868236
TI  - Neoadjuvant therapy for rectal cancer: improved tumor response, local recurrence,
      and overall survival in nonanemic patients.
AB  - INTRODUCTION: Preoperative, long-course chemoradiotherapy is recommended for
      rectal cancers involving or threatening the mesorectal resection margin, but
      tumor response is variable. Some highly radiosensitive cancers completely
      regress, leading to reduced local recurrence and improved survival. This study
      was designed to evaluate the influence of anemia during chemoradiotherapy on
      tumor response, local and distant recurrence, and overall survival. METHODS: Mean
      hemoglobins during chemoradiotherapy of consecutive patients with rectal cancer
      undergoing chemoradiotherapy and surgery were calculated and ranked. Anemia was
      defined as lowest quartile for males and females. Tumor response was
      histologically quantified using rectal cancer regression grade. RESULTS: Of 100
      patients, 5 females and 20 males were anemic. Nonanemic patients achieved better
      tumor response (54 percent regression Grade 1) than anemic patients (28 percent,
      P = 0.028). There were more locally advanced cancers in anemic (48 percent T4)
      compared with nonanemic patients (21 percent T4), but radiologic T stage did not
      influence tumor response (50 percent T3 vs. 43 percent T4 regression Grade 1, P =
      0.53) or overall survival. Mesorectal margin positivity was less in nonanemic (15
      percent) compared with anemic patients (36 percent, P = 0.021). At median follow
      up of 39 months, nonanemic patients (7 percent) suffered less local recurrence
      than anemic patients did (38 percent, P = 0.003). Overall survival at two years
      was improved in nonanemic (91 percent) compared with anemic patients (64 percent,
      P = 0.021), but was similar for T3 and T4 patients. CONCLUSIONS: Patients with
      normal hemoglobin during chemoradiotherapy achieved better tumor response, less
      local recurrence, and improved overall survival compared with anemic patients,
      independent of radiologic T stage. Correcting anemia before chemoradiotherapy
      might improve tumor response and oncologic outcomes.

PMID- 15868237
TI  - A 10-year outcomes evaluation of mucinous and signet-ring cell carcinoma of the
      colon and rectum.
AB  - PURPOSE: Most studies examining mucinous or signet-ring cell colorectal cancers
      are single institution reports. This study used a national cancer registry to
      analyze the epidemiology and survival outcomes of these two subtypes of
      colorectal cancer compared with adenocarcinoma tumors. METHODS: All patients
      diagnosed with mucinous (n = 16,991), signet-ring cell (n = 1,522), or
      adenocarcinoma (n = 146,115) colorectal cancer in the Surveillance, Epidemiology,
      and End Results database (1991-2000) were evaluated. Analyses were performed to
      obtain age-adjusted incidence rates, stage at presentation, tumor grade, and five
      year relative survival for each subtype. RESULTS: Mucinous were slightly more
      common in females (53.4 percent). Incidence rates per 100,000 persons were:
      mucinous, 5.5; signet-ring cell, 0.6; and adenocarcinoma 46.6. The annual percent
      change during ten years was stable for mucinous, increased for signet-ring cell
      (4.8 percent; P < 0.05), and decreased for adenocarcinoma (-1.1 percent; P <
      0.05). Fewer mucinous (18 percent) and signet-ring cell (21 percent) tumors were
      located in the rectum compared with adenocarcinoma (29 percent). Signet-ring cell
      presented at later stage (III/IV, 80.9 percent) more often than mucinous (52.8
      percent) and adenocarcinoma (49.5 percent), and also had worse tumor grade (high
      grade: signet-ring cell, 73.5 percent; mucinous, 20.9 percent; adenocarcinoma,
      17.5 percent). Relative five-year survival was worse for signet-ring cell than
      mucinous or adenocarcinoma. CONCLUSIONS: We present a large population-based
      review of colorectal cancer subtypes by analyzing national data from the past
      decade. Although the incidence of colorectal adenocarcinoma is decreasing in the
      United States, mucinous and signet-ring cell subtypes are stable and increasing,
      respectively. Importantly, it seems that the signet-ring cell subtype has worse
      outcomes, whereas survival rates for mucinous tumors are similar to
      adenocarcinomas.

PMID- 15868238
TI  - Endoscopic transanal rectal mucosal ablation in the surgical treatment of
      ulcerative colitis: preliminary results of a novel technique.
AB  - PURPOSE: We describe a new technique that endoscopically eradicates rectal stump
      mucosa after total colectomy for ulcerative colitis. METHODS: Seven patients (5
      males; median age, 56 (range, 36-72) years) underwent attempted endoscopic
      transanal rectal mucosal ablation using the 28-French-gauge urologic
      resectoscope, either at the time of total colectomy and ileostomy for failed
      medical therapy (5 patients) or as an alternative to completion proctectomy (2
      patients) with rectal stump discharge. All had declined restorative
      proctocolectomy. Clinical, endoscopic, and histologic follow-up was undertaken
      during a mean of 15 (range, 3-28) months. RESULTS: The operative technique
      evolved during these cases; mucosal ablation was successfully performed leaving a
      denuded muscular rectal tube in situ in six patients. Mean operative time was 45
      minutes. Postoperative endoscopic surveillance has not demonstrated any viable
      rectal mucosa in these six patients, with only granulation tissue detected
      histologically. Narrowing of the rectal tube has occurred in two patients.
      Although all patients report insignificant rectal discharge, urinary and sexual
      function have remained unchanged. CONCLUSIONS: Diathermy ablation of the rectal
      mucosa via endoscopic transanal rectal mucosal ablation avoids the complications
      of pelvic dissection and might offer an effective alternative to proctectomy for
      ulcerative colitis.

PMID- 15868239
TI  - Fibrin glue in the treatment of pilonidal sinus: results of a pilot study.
AB  - INTRODUCTION: Pilonidal sinus is a common condition of uncertain etiology. There
      is no agreed best surgical treatment. Treatment of fistula-in-ano has been
      described with some success with fibrin tissue glue. The use of fibrin glue is
      investigated in this pilot study. METHODS: Six patients with chronic pilonidal
      sinus were treated with injection of fibrin tissue glue after curettage of the
      pits. RESULTS: There were no complications. Postoperative discomfort was minimal
      and early return to normal activities was possible. There was no recurrence of
      disease in five of six patients at one year. CONCLUSIONS: Fibrin tissue glue may
      be a possible novel treatment for pilonidal disease.

PMID- 15868240
TI  - Endorectal ultrasound in the management of patients with malignant rectal polyps.
AB  - PURPOSE: This study was designed to determine the efficacy of endorectal
      ultrasound in the management of patients with malignant rectal polyps removed by
      snare excision during colonoscopy. METHODS: A retrospective review of the medical
      records and endorectal ultrasound images of 63 patients with endoscopically
      removed rectal polyps containing invasive adenocarcinoma subsequently staged by
      endorectal ultrasound. Patients underwent surgery or were followed at a single
      institution. The polyp characteristics and ultrasound images were compared with
      the presence of residual tumor in the surgical specimen in patients who underwent
      further surgery or with recurrence in patients who did not. RESULTS: The
      morphology of the polyps was described in 31 patients (49 percent); they were
      sessile in 26 (41 percent) and pedunculated in 6 (9 percent). The margins were
      positive in 22 patients (35 percent), negative in 19 (30 percent), and not
      specified in 22 (35 percent). Most tumors were well or moderately differentiated;
      only 3 (5 percent) were poorly differentiated. Thirty-three patients underwent
      further surgery (3 low anterior resection, and 30 transanal excision); 30 had no
      further surgery. The accuracy of endorectal ultrasound in assessing the presence
      of residual cancer in the rectal wall in patients who had surgery was 54 percent,
      with a 39 percent positive predictive value and 65 percent negative predictive
      value. Endorectal ultrasound accurately identified metastatic lymph nodes in two
      of three patients who had radical surgery. Endorectal ultrasound was more useful
      than polyp morphologic or histologic criteria to determine the presence of
      residual cancer in the rectal wall. CONCLUSIONS: Endorectal ultrasound does not
      definitely exclude the possibility of residual tumor in the rectal wall or
      mesenteric nodes of patients who had a malignant polyp snared endoscopically.
      Consequently, decisions regarding the definitive management of these patients
      cannot be based exclusively on the endorectal ultrasound images of the
      polypectomy site.

PMID- 15868241
TI  - Infrared coagulator: a useful tool for treating anal squamous intraepithelial
      lesions.
AB  - PURPOSE: The incidence of invasive anal squamous carcinoma in men who have sex
      with men is rising, particularly in those with human immunodeficiency virus. As
      in the cervix the high-grade squamous intraepithelial lesion is thought to be an
      invasive squamous cell carcinoma precursor. Cervical high-grade squamous
      intraepithelial lesions are treated by removing the squamocolumnar transition
      zone. This is not possible in the anus, where treatment is often surgical and is
      accompanied by significant pain and morbidity. Better office-based techniques to
      treat anal high-grade squamous intraepithelial lesions are needed. We employed
      the infrared coagulator in an office setting to ablate high-grade squamous
      intraepithelial lesions. METHODS: A retrospective review of medical records was
      performed on 68 human immunodeficiency virus-positive men who have sex with men
      who underwent infrared coagulator ablation of biopsy-proven high-grade dysplasia
      from the time we began using the procedure in 1999. All patients have had at
      least six months of follow-up. Procedures were performed with local anesthesia on
      patients with discrete high-grade squamous intraepithelial lesions. Follow-up
      consisted of anal cytology with high-resolution anoscopy and biopsy of suspicious
      areas every three to six months. New or recurrent high-grade dysplasia was
      retreated. Patients with circumferential or bulky disease were treated in the
      operating room and were excluded from the study. RESULTS: Altogether, 68 patients
      met the enrollment criteria. The median patient age was 41 years (range 29-62
      years). A total of 165 lesions were treated (mean 1.6 lesions, range 1-5) and
      only 46 (28 percent) persisted. However, 44 patients (65 percent) developed a new
      or persistent high-grade squamous intraepithelial lesion within a median time of
      217 days (range 27-566 days) after infrared coagulation. The remaining 24
      patients (35 percent) were free of high-grade dysplasia for a median of 413 days
      (range 162-1313 days) after infrared coagulation. When patients were treated a
      second or third time, the incidence of new or persistent high-grade dysplasia
      dropped to 58 percent and 40 percent, respectively. The probability of curing a
      retreated lesion was 72 percent. Using generalized estimating equations, the
      incidence of high-grade dysplasia decreased with repeated infrared coagulator
      treatments. No patient developed squamous-cell carcinoma, had a serious adverse
      event, or developed anal stenosis. CONCLUSIONS: The infrared coagulator is a
      safe, office-based modality for treating anal high-grade squamous intraepithelial
      lesion in human immunodeficiency virus-positive men who have sex with men.
      Successive treatments led to decreased recurrence rates.

PMID- 15868242
TI  - Long-term function after restorative proctocolectomy.
AB  - PURPOSE: Early functional outcome after restorative proctocolectomy and formation
      of an ileoanal pouch is known to be good, but there are minimal data on the long
      term function of the pouch. The aim of this study was to look at the long-term
      functional outcome in patients who had undergone restorative proctocolectomy and
      formation of an ileoanal pouch. METHODS: A total of 151 consecutive patients (96
      males, 55 females) who underwent ileoanal pouch surgery between April 1983 and
      May 1993 were identified. Functional outcomes from the previous 12 months were
      appraised by a standardized questionnaire. RESULTS: The median age at surgery was
      31 years (range, 6-63 years), with a median follow-up of 142 months (range, 100
      221 months). Eighteen patients have had their pouches excised, with another
      patient being defunctioned. Therefore 19 patients (13 percent) had suffered pouch
      failure. Altogether, 115 patients were available for follow-up, and 98 patients
      (85 percent) returned questionnaires. The median pouch-emptying frequency was
      five times (range, 1-17) during the day and one time (range, 0-6) at night. A
      total of 74 percent of patients had perfect continence during the day. Most of
      the patients had no life-style restrictions related to the pouch, and 98 percent
      of patients would recommend a pouch to others. CONCLUSIONS: Long-term functional
      outcome after ileoanal pouch surgery is good in most patients. For patients
      requiring proctocolectomy, ileoanal pouch surgery can now be recommended as an
      excellent long-term option.

PMID- 15868243
TI  - Pouch-vaginal fistula after ileal pouch-anal anastomosis: treatment and outcomes.
AB  - PURPOSE: Pouch-vaginal fistula is an uncommon but serious complication after
      ileal pouch anal anastomosis. The management of pouch-vaginal fistulas is
      challenging and a number of treatment options exist. The purpose of this study
      was to examine the outcomes after various procedures for pouch-vaginal fistula
      performed at our institution. METHODS: Patients who were treated for pouch
      vaginal fistula at Mount Sinai Hospital were identified from a prospectively
      maintained database. Demographic, disease history, treatment, and outcomes data
      were obtained. Treatment success was defined as no recurrence of the fistula with
      a functioning pouch and no ileostomy. RESULTS: Since November 1982, 24 of 619
      (3.9 percent) women who had primary ileal pouch-anal anastomosis performed at
      Mount Sinai Hospital developed a pouch-vaginal fistula. Five women had ileal
      pouch-anal anastomosis performed at another institution and were referred for
      management of their pouch-vaginal fistula. Local and/or combined abdominoperineal
      repairs were performed in 22 of 29 patients. Combined abdominoperineal repairs
      were associated with a higher success rate than that of local perineal repairs
      (52.9 vs. 7.9 percent, respectively, at 10 years after repair; p = 0.035).
      Overall, 50 percent (11/22) of patients who underwent surgical repair of a pouch
      vaginal fistula had a successful result with a functioning pouch and no
      recurrence of the fistula, and 21 percent (6/29) of patients required pouch
      excision. CONCLUSIONS: The management of pouch-vaginal fistula after ileal pouch
      anal anastomosis is associated with a high recurrence rate. Combined
      abdominoperineal repair appears to offer better results than those of local
      procedures.

PMID- 15868244
TI  - Patients' views of a colostomy for fecal incontinence.
AB  - INTRODUCTION: Formation of a permanent stoma often is seen as a last resort when
      all other interventions for fecal incontinence have failed. However, no previous
      study has examined patients' views of a colostomy to manage fecal incontinence.
      METHODS: People who had a colostomy to manage fecal incontinence were recruited
      via an advertisement in the magazine of the British Colostomy Association or from
      those operated at a specialist colorectal hospital. Four questionnaires were
      sent, asking about the stoma, previous incontinence, anxiety and depression, and
      quality of life. RESULTS: A total of 69 replies were received. Respondents were
      11 males and 58 females with a median age of 64 years and a median of 59 months
      since the operation. Rating their ability to live with their stoma now on a scale
      of 0 to 10, the median response was 8 (range, 0-10). The majority (83 percent)
      felt that the stoma restricted their life "a little" or "not at all" (a
      significant improvement from perceived restriction from former incontinence, P =
      0.008). Satisfaction with the stoma was a median of 9 on a scale of 0 to 10
      (range, 0-10). Eighty-four percent would "probably" or "definitely" choose to
      have the stoma again. Quality of life (SF-36) was poor, but neither depression
      nor anxiety was a prominent feature. CONCLUSIONS: The majority of previously
      incontinent people were positive about the stoma and the difference it had made
      to their life. However, a few had not adapted and disliked the stoma intensely.
      Health care professionals should discuss a stoma as an option with patients whose
      lives are restricted by fecal incontinence.

PMID- 15868245
TI  - Failure of conservative management after the passage of a distal colonic "cast":
      report of a case.
AB  - PURPOSE: The spontaneous passage per rectum of a full-thickness colon "cast" is a
      rare consequence of acute colonic ischemia. Previous cases have undergone surgery
      soon afterward because of intractable symptoms. We report a patient who was
      managed conservatively for 11 months but ultimately required definitive surgery.
      METHODS: The clinical, radiographic, pathologic, and endoscopic findings were
      obtained from the case notes and compared with previously reported cases.
      RESULTS: A 67-year-old obese patient underwent a Hartmann's procedure for a
      perforated diverticular abscess, which was reversed six months later. On the
      first postoperative night after the reversal, she had a brief hypotensive
      episode, and three weeks later passed a 21-cm, full-thickness infarcted piece of
      colon. She did not develop peritonitis and for 11 months experienced only mild
      symptoms. Under colonoscopic surveillance, the granulation tissue conduit
      connecting the remaining viable bowel became increasingly stenosed proximally and
      difficult to dilate. After three rapidly consecutive episodes of large-bowel
      obstruction, she required a laparotomy to resect the stricture and restore bowel
      continuity. From a literature review, this is the eighth case of its kind and the
      first in which such prolonged conservative management has been possible.
      CONCLUSIONS: When symptoms permit, it is feasible to manage patients
      conservatively in the short-term after this unusual event to allow recovery from
      the initial insult and planning of future surgery. However, definitive treatment
      is surgical and colonoscopic management should not delay this once the patient is
      fit for surgery.

PMID- 15868247
TI  - Impact of video colonoscopy on stage and outcome of patients with symptomatic
      colorectal cancer.

PMID- 15868248
TI  - Precoating of alloplastic materials with living human fibroblasts--a feasibility
      study.
AB  - BACKGROUND: The use of alloplastic materials such as polypropylene and polyester
      has reduced the recurrence of abdominal wall hernias. Concomitantly, new problems
      have arisen such as inflammatory response against the implanted material and the
      development of enteric fistulas in case of direct contact of the bowel to
      polypropylene and polyester. A precoating of the PP with collagen and other
      absorbable materials seems to reduce the incidence of adhesions and fistulas. The
      aim of this study was to show the technical feasibility of a precoating of
      polypropylene with living human fibroblasts and to investigate the growth
      properties of the cells under these conditions in vitro. METHODS: The textile
      structure of three different alloplastic materials is described (SurgiPro),
      TycoHealthcare; Parietene3 PP1510, Dallhausen; VIPRO II, Ethicon Endosurgery).
      Enhanced Green Fluorescence Protein (EGFP) transduced human foreskin fibroblasts
      (KiF5) were seeded onto these different alloplastic materials. Proliferation was
      analyzed by FACS analysis of Ki67 expression. The coating process of the whole
      mesh area was observed over time with UV-light microscopy, immunostaining, and
      scanning electron microscopy (SEM). The expression of collagen type I and III was
      investigated by immunostaining. RESULTS: The three alloplastic materials used
      were knitted fabrics with different textile structures. KiF5 colonized the entire
      alloplastic material within 4-6 weeks. Cells were proliferating, as detected by
      Ki67 expression. SEM showed surface ruffles and long cellular extensions,
      indicating an active cell metabolism. Light microscopy and SEM suggested that the
      cells modify the apolar surface by deposition of extracellular matrix components
      before colonization. CONCLUSION: Our study shows the feasibility of precoating of
      polypropylene meshes with living human fibroblasts and opens the possibility for
      clinical use in the future.

PMID- 15868249
TI  - Variant Creutzfeldt-Jakob disease: a cause for concern. Review of the evidence
      for risk of transmission through abdominal lymphoreticular tissue surgery.
AB  - BACKGROUND: Concern has long existed regarding the possible iatrogenic spread of
      variant Creutzfeldt-Jakob disease (v-CJD) through surgery. This had been fueled
      by recent reports of bovine spongiform encephalopathy in U.S. cattle and the
      first probable case of blood transmission of v-CJD in the UK. METHODS: Systematic
      review of experimental and nonexperimental studies. Studies identified from
      searches of Medline, Embase, Cochrane Library, Science Citation Index medical
      databases, searching bibliographies of retrieved papers, and personal
      communication with international experts in the field. RESULTS: Six articles
      satisfied our search criteria. Evidence stems from case reports, case series, and
      cross-sectional studies. There are no published cases of surgically transmitted v
      CJD. CONCLUSION: We found evidence of v-CJD prion agents in the spleen, appendix,
      rectum, and adrenal glands of affected patients and evidence of v-CJD prion in
      the appendix of patients in the preclinical stage of the disease. The risk of
      transmission of v-CJD prion during abdominal surgery is currently unquantifiable.

PMID- 15868250
TI  - Laparoscopic-assisted ileo-colectomy for tuberculosis.
AB  - BACKGROUND: Laparoscopic-assisted colon resection (LACR) for benign disease has
      gained acceptance and has a lower morbidity than open surgery. Reports in Western
      literature have outlined the use of LACR for diverticulosis, ulcerative colitis,
      and Crohn's disease. We evaluated the use of LACR in patients with ileo-cecal
      tuberculosis (IC-TB) and describe our technique and results. METHODS: Twenty-six
      patients (20 F) between 16 and 45 years of age underwent a LACR for IC-TB over a
      4-year period. Three access ports were used in 22 patients, four patients needed
      four ports. The cecum, ascending colon, proximal transverse colon, and terminal
      ileum were mobilized completely. The right colic vessels were divided
      intracorporeally. The specimen was delivered using a 5- to 6-cm incision. The
      ileo-colic pedicle and bowel were divided outside and an ileocolic anastomosis
      performed. After placing the bowel within the abdomen the pneumoperitoneum was
      recreated, saline irrigation done, and hemostasis achieved. RESULTS: No patient
      needed a formal laparotomy. Peristalsis returned within 48 h in 19 patients and
      after 72 h in the remaining seven. Oral liquids were started on all patients by
      the 3rd postoperative day (POD) and a soft diet by the 5th POD. Twenty patients
      had a bowel movement by the 4th POD and the rest by the 5th POD. Eighteen
      patients were discharged by the 5th day and the remaining by the 7th day. Three
      patients developed wound sepsis. Twenty-one patients could resume normal activity
      within 2 weeks, the rest within a month. CONCLUSION: Laparoscopic-assisted colon
      resection seems to be an ideal operation for patients with ileo-cecal
      tuberculosis. It has minimal morbidity and allows a quick return to normal
      activity.

PMID- 15868251
TI  - Technical skills errors in laparoscopic cholecystectomy by expert surgeons.
AB  - BACKGROUND: Performing laparoscopic surgery involves a complex cascade of
      cognitive skills, which may inherently have a constant technical error rate. We
      assess generic and specific minor and major error rates in laparoscopic
      cholecystectomies (LCs) performed by consultant surgeons. METHODS: Checklists of
      generic (11) and specific technical minor (six) and major events (eight) were
      devised for LCs. Two experienced surgeons assessed each full-length operation
      blindly and independently. RESULTS: A total of 37 LCs were performed by eight
      consultants. There were no major intraoperative or postoperative complications.
      Mean inter-rater reliability was kappa = 0.91 (range 0.80-0.98) for each of the
      error categories. Error rates were generic (27/407) 6.6%, minor (59/222) 26.6%,
      and major (8/296) 2.7%, respectively. There was a significant statistical
      difference between the minor error group and the other groups, p <or= 0.05.
      CONCLUSIONS: Performing laparoscopic surgery may always have a background
      technical error rate. Our present study demonstrates a migration of surgical
      technical errors in expert laparoscopic surgeons. The surgeons migrate
      technically when they execute a high rate of procedure-specific minor errors.
      However, when it comes to the major fundamental aspects of the operation, they
      dynamically adapt and migrate away from performing major technical errors. We aim
      to continue the study to increase cases, assess trainees as well, and also
      explore other factors that may affect the surgeon when executing surgical
      technical tasks.

PMID- 15868252
TI  - Does topical GTN on the sphincter of Oddi facilitate ERCP? A double-blind
      randomized control trial.
AB  - BACKGROUND: Endoscopic retrograde cholangio pancreatography (ERCP) is a
      technically challenging procedure. Glyceryl trinitrate (GTN) has been shown to
      reduce tone in the sphincter of Oddi (SO), cannulation of which is a rate
      limiting factor. A double-blind randomized control trial was performed to assess
      whether topical GTN on the SO would facilitate cholangiography and/or bile duct
      cannulation. METHODS: 104 patients requiring ERCP for biliary symptoms were
      randomized into two groups, 52 controls pretreated with 5 ml 0.9% normal saline
      (NS) and 52 pretreated with 5 ml GTN (concentration 1 mg/ml). RESULTS: There was
      no significant between the control group and the GTN group in primary cannulation
      rate (p = 0.76), time taken to cholangiography (p = 0.58), or time to cannulation
      (p = 0.43). CONCLUSION: Topically administered GTN to the SO does not aid in
      obtaining a cholangiogram or cannulation during an ERCP.

PMID- 15868253
TI  - Laparoscopic adrenalectomy for malignant neoplasm: our experience in 15 cases.
AB  - BACKGROUND: We report our experience with laparoscopic adrenalectomy (LA) for
      malignant pathologies that in some cases required a multiorgan resection.
      METHODS: In this study, we retrospectively reviewed a group of 15 patients (10
      men, and five women) who underwent an operation for primitive or metastatic
      adrenal malignant tumors. RESULTS: The sizes of the lesions ranged from 3.5 to
      8.5 cm (average 3.6). We performed 11 adrenalectomies (four right and seven
      left), two left adrenalectomies with distal spleno-pancreatectomy, one right
      adrenalectomy with nephrectomy, and one laparoscopic exploration that showed a
      peritoneal spreading. Six patients, with a follow-up ranging from 3 to 24 months
      (mean 13.6 months), are disease free; the others developed metastatic repetitions
      or local recurrences. CONCLUSIONS: LA could be performed always respecting the
      oncological principles of radical excisions. This approach in our patients has
      been associated with low morbidity, low intraoperative blood loss, short hospital
      stay, and fast functional recovery.

PMID- 15868254
TI  - Laparoscopic surgery for common surgical emergencies: a population-based study.
AB  - BACKGROUND: Despite being controversial in the past, many reports on the safe use
      of laparoscopic surgery in emergency settings have been published. The aim of
      this study was to investigate the diffusion of laparoscopic surgery in three
      common surgical emergency operations, namely, appendectomy, cholecystectomy, and
      simple repair of perforated peptic ulcer (PPU), in a stable population. METHODS:
      This was a retrospective analysis of the central database of the Hospital
      Authority (HA) in Hong Kong. Data for patients managed in 14 HA hospitals from
      1998 to 2002 were studied. The operation record and discharge record of each
      patient were also investigated to verify the data. RESULTS: A total of 12,708
      patients underwent appendectomy, 2631 patients underwent cholecystectomy, and
      2260 patients had simple repair of PPU performed. During the study period, 37.2%
      of appendectomies, 46.5% of cholecystectomies, and 23.1% of simple repairs of PPU
      were performed laparoscopically. More than a two-fold increase in the proportion
      of laparoscopic surgery was observed in each of these three operations. By the
      end of 2002, the percentage of laparoscopic surgery had increased to 53.5% for
      appendectomies, 61.3% for cholecystectomies, and 32.9% for simple repairs of PPU.
      Significantly lower hospital mortality rates and shorter postoperative hospital
      stay were consistenty observed in patients with laparoscopic surgery of the three
      emergencies. A wide variation in the use of laparoscopic surgery, ranging from
      3.7% to 73.1%, was observed among the 14 HA hospitals. However, there was no
      correlation in the use of laparoscopic surgery with the volume of operation
      performed in each hospital (p = 0.933). CONCLUSION: A high diffusion rate on the
      use of laparoscopic surgery for common surgical emergency was observed in Hong
      Kong. However, there was also a wide variation in the diffusion rate among the 14
      HA hospitals. Efforts to reduce hospital variation for the better dissemination
      of safe laparoscopic technique may be warranted.

PMID- 15868255
TI  - Temporary stenting of acquired benign tracheoesophageal fistulas in critically
      ill ventilated patients.
AB  - BACKGROUND: To evaluate the use of esophageal stents for temporary sealing of
      acquired benign tracheoesophageal fistulas developed in critically ill,
      ventilated patients. METHODS: This is a retrospective analysis (1992-2003) of the
      data of 12 mechanically ventilated patients - six of them after major or multiple
      trauma - being intubated for a median of 30 days before they develop an acquired
      benign tracheoesophageal fistula. Five of them were in sepsis. Two types of
      stents were used: the Wilson-Cook esophageal balloon plastic stent in the first
      four cases and the Ultraflex covered self-expandable stent in the remaining
      eight. The total procedure was performed at bedside in the intensive care unit,
      with no special need for supplementary anesthesia or fluoroscopic control.
      RESULTS: Stent implantation was technically successful in all patients and
      fistula occlusion was achieved in every case. There was no stent migration and
      fistulas remained sealed until death or upon decision for removal. Nine patients
      died between 5 days and 2 months after stent placement, as a result of their
      diseases. Three patients were referred for fistula surgical repair 33, 36, and 43
      days after stent placement. Before surgery the stents were easily removed under
      direct vision. CONCLUSION: Temporary closure of an acquired tracheoesophageal
      fistula developed in critically ill ventilated patients is an easy, bedside
      applicable, safe, and effective palliative procedure, with no complications or
      mortality.

PMID- 15868256
TI  - Laparoscopic resection for rectal cancer: outcomes in 194 patients and review of
      the literature.
AB  - BACKGROUND: There are few reports on laparoscopic rectum resection demonstrating
      its feasibility and efficacy in patients with rectal cancer. Most patient series
      are small, and results must be considered preliminary and medium-term. Our large
      prospective conducted study aimed to assess the effectiveness of a totally
      laparoscopic resection for rectum carcinoma with emphasis on perioperative and
      long-term oncological outcomes. METHODS: Between November 1992 and July 2003, 194
      unselected patients were resected laparoscopically for rectal carcinoma. Patients
      with locally advanced rectum carcinoma (uT3/uT4) and no evidence of distant
      metastases were candidates for neoadjuvant chemoradiation. Adjuvant treatment was
      administered to patients with UICC stage II/III disease. All patients were
      followed up prospectively to evaluate complications and late outcomes. Survival
      probability analysis was performed using the Kaplan-Meier method. Study selection
      was made by Medline search using the following key words: rectal cancer, rectal
      neoplasms, laparoscopy, and resection. Single case reports and abstracts were
      excluded. When surgical series were reported more than once, only the most recent
      reports were considered and listed. RESULTS: The most common procedures were low
      anterior resection with total mesorectum excision in 65.5% of patients and high
      anterior resection in 25.3%. Average operative time was 174 min. Average number
      of lymph nodes removed was 25.4 and length of specimen resected was 27.6 cm.
      Resection was curative in 145 patients and palliative in 49 cases. UICC tumor
      stages were as follows: stage I: 25.2%, stage II: 27.3%, stage III: 30.4%, and
      stage IV: 17%. Intraoperative complications were <1% for lesions of the ureter,
      urinary bladder, and deferent duct. Conversion to conventional surgery was
      necessary in two cases (1%). The most common postoperative complication was
      anastomotic leakage in 13.5% of patients. There was no postoperative mortality.
      Follow-up evaluation ranged from 1 to 128 months with a mean of 46.1 months. The
      most common late complication was incisional hernia in 3.6% of patients. Port
      site metastases occurred in one patient (0.5%). Tumor recurrence developed in 23
      of the 145 curative resected patients (11.7% distant metastases and 4.1% local
      recurrence). Overall local recurrence rate was 6.7% (4.1% after curative
      resection and 14.3% after palliative resection). Overall survival rate was 90.6%
      at 1 year, 74.5% at 3 years, and 66.3% at 5 years. Overall 5-year survival rate
      was 76.9% after curative resection and 31.8% after palliative resection. Cancer
      related survival rate was 94% at 1 year, 82.4% at 3 years, and 78.9% at 5 years.
      At 5 years it was 87.7% after curative resection and 48.5% after palliative
      resection. At 5 years, the survival rate was 100% for stage I, 94.4% for stage
      II, 66.6% for stage III, and 44.6% for stage IV. CONCLUSIONS: Our results and the
      literature review clearly demonstrate that laparoscopic resection for rectal
      cancer is not associated with higher morbidity and mortality. Established
      oncological and surgical principles are respected and long-term outcomes are at
      least as good as those after open surgery.

PMID- 15868257
TI  - Endoscopic resection of gastrointestinal submucosal tumors assisted by endoscopic
      ultrasonography.
AB  - BACKGROUND: The resection and histologic examination of the lesions is generally
      considered the treatment of choice in order to achieve diagnosis in
      gastrointestinal submucosal tumors. Moreover, the degree of malignancy of the
      tumor depends on certain features that can only be studied on the entire resected
      piece. METHODS: We revised the cases of patients who underwent endoscopic
      resection of gastrointestinal submucosal tumors in the period from 1997 through
      2002. RESULTS: Fifty submucosal lesions were resected in 45 patients (64.4% men).
      Patient mean age was 55.31 years. Of the lesions, 52% were gastric tumors and 88%
      were located in the second layer. Mean size was 12.34 mm, and 54% were smaller
      than 10 mm. Resection with submucosal injection of saline solution and diluted
      adrenaline was performed on 46% of the lesions, and standard resection using
      polypectomy snare on 48%. Ligation was used in three cases. Resection was
      successful in 98% and major complications were observed in 4% (two cases of
      bleeding, endoscopically resolved). CONCLUSIONS: The endoscopic resection of
      submucosal tumors is a safe and efficient technique: It has few associated
      complications and allows diagnosis in all the cases and cure of the lesion in the
      great majority of cases.

PMID- 15868258
TI  - Telerobotic-assisted laparoscopic hysterectomy for benign and oncologic
      pathologies: initial clinical experience with 30 patients.
AB  - BACKGROUND: Telerobotic-assisted laparoscopic attempts to provide technological
      solutions to the inherent limitations of traditional laparoscopic surgery. The
      aim of this study is to report the first experience of two teams concerning
      telerobotic-assisted laparoscopic hysterectomy for benign and malignant
      pathologies. METHODS: This study included 14 patients at the University Hospital
      Saint Pierre of Brussels (Belgium) and 16 patients at the Cancer Center of Nancy
      (France) from September 1999 to July 2003. RESULTS: The indications for surgery
      were uterine malignant diseases in 12 cases (stade I) (41%), and benign
      pathologies of the uterus in 18 cases (59%). Five postoperative complications
      (17%) occurred, none related to the robotic system. CONCLUSION: Robotic surgery
      can be safely performed in gynecologic and gynecologic-oncologic surgery with no
      increase in complication rates. A significant advance is represented by the
      surgeon's ergonomic improvement.

PMID- 15868259
TI  - Do patient or hospital demographics predict cholecystectomy outcomes? A
      nationwide study of 93,578 patients.
AB  - BACKGROUND: The purpose of this study was to examine the influence of patient and
      hospital demographics on cholecystectomy outcomes. METHODS: Year 2000 data from
      the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database
      was obtained for all patients undergoing inpatient cholecystectomy at 994
      nationwide hospitals. Differences (p < 0.05) were determined using standard
      statistical methods. RESULTS: Of 93,578 cholecystectomies performed, 73.4% were
      performed laparoscopically. Length of hospital stay (LOS), charges, morbidity,
      and mortality were significantly less for laparoscopic cholecystectomy (LC).
      Increasing patient age was associated with increased LOS, charges, morbidity,
      mortality, and a decreased LC rate. Charges, LOS, morbidity, and mortality were
      highest for males with a lower LC rate than for females Mortality and LOS were
      higher, whereas morbidity was lower for African Americans than for whites.
      Hispanics had the shortest LOS, as well as the lowest morbidity and mortality
      rates. Laparoscopic cholecystectomy was performed more commonly for Hispanics
      than for whites or African Americans, with lower charges for whites. Medicare
      insured patients incurred longer LOS as well as higher charges, morbidity, and
      mortality than Medicaid, private, and self-pay patients, and were the least
      likely to undergo LC. As median income decreases, LOS increases, and morbidity
      decreases with no mortality effect. Teaching hospitals had a longer LOS, higher
      charges, and mortality, and a lower LC rate, with no difference in morbidity,
      than nonteaching centers. As hospital size (number of beds) increased, LOS, and
      charges increased, with no difference in morbidity. Large hospitals had the
      highest mortality rates and the lowest incidence of LC. Urban hospitals had
      higher LOS and charges with a lower LC rate than rural hospitals. After control
      was used for all other covariates, increased age was a predictor of increased
      morbidity. Female gender, LC, and intraoperative cholangiogram all predicted
      decreased morbidity. Increased age, complications, and emergency surgery
      predicted increased mortality, with laparoscopy and intraoperative cholangiogram
      having protective effects. Patient income, insurance status, and race did not
      play a role in morbidity or mortality. Academic or teaching status of the
      hospital also did not influence patient outcomes. CONCLUSIONS: Patient and
      hospital demographics do affect the outcomes of patients undergoing inpatient
      cholecystectomy. Although male gender, African American race, Medicare-insured
      status, and large, urban hospitals are associated with less favorable
      cholecystectomy outcomes, only increased age predicts increased morbidity,
      whereas female gender, laparoscopy, and cholangiogram are protective. Increased
      age, complications, and emergency surgery predict mortality, with laparoscopy and
      intraoperative cholangiogram having protective effects.

PMID- 15868260
TI  - Transanal endoscopic versus total mesorectal laparoscopic resections of T2-N0 low
      rectal cancers after neoadjuvant treatment: a prospective randomized trial with a
      3-years minimum follow-up period.
AB  - BACKGROUND: This study aimed to compare the results and the oncologic outcomes of
      transanal endoscopic microsurgery (TEM) with neoadjuvant radiochemotherapy and
      laparoscopic resection (LR), also with neoadjuvant radiochemotherapy, in the
      treatment of T(2)-N(0) low rectal cancer. METHODS: The study enrolled 40 patients
      with T2-N(0) rectal cancer, randomizing 20 to TEM (arm A) and 20 to LR (arm B).
      RESULTS: After neoadjuvant radiochemotherapy, tumor downstaging was observed for
      13 patients (65%) in arm A (7 pT0 and 6 pT1) and in 11 patients (55%) in arm B (7
      pT0 and 4 pT1). More than a 50% reduction of the tumor diameter was observed in
      four arm A cases and in six arm B cases. At a median follow-up period of 56
      months (range, 44-67 months) in both arms, one local failure (5%) occurred after
      6 months in arm A and one (5%) after 48 months in arm B. Distant metastases
      occurred in one arm A patient (5%) after 26 months of follow-up evaluation and in
      one arm B patient (5%) at 31 months. The probability of local or distant failure
      was 10% for TEM and 12% for laparoscopic resection, whereas the probability of
      survival was 95% for TEM and 83% for laparoscopic resection. CONCLUSIONS: The
      findings show comparative results between the two study arms in terms of
      probability of failure and survival.

PMID- 15868261
TI  - Laparoscopic revisional bariatric surgery: myths and facts.
AB  - BACKGROUND: Bariatric surgery is growing worldwide. An increasing number of
      patients will require revisional procedures because of inadequate weight control,
      complications, or loss of quality of life. METHODS: From August 1999 to September
      2003, 62 patients were submitted to laparoscopic revisional surgery. RESULTS: The
      primary operations consisted of laparoscopic adjustable gastric banding in 39
      cases, banded and nonbanded Roux-en-Y gastric bypass (RYGB) in 17 cases, vertical
      banded gastroplasty in 4 cases, and biliopancreatic diversion in 2 cases.
      Although technically demanding, laparoscopic conversion to RYGB was possible in
      all cases. Mean operative time was 100 min. Mean hospital stay was 77 h. There
      were no intraoperative or postoperative complications. A good body mass index
      reduction after the revisional procedure was observed with a 24 month follow-up
      period. CONCLUSIONS: Laparoscopic revisional bariatric surgery is safe and
      effective. However, it should be performed only by experienced bariatric and
      laparoscopic surgeons.

PMID- 15868262
TI  - Leveling the learning curve for laparoscopic bariatric surgery.
AB  - BACKGROUND: The learning curve for laparoscopic bariatric surgery is associated
      with increased morbidity and mortality. METHODS: The study included the first 100
      patients undergoing laparoscopic Roux-en-Y gastric bypass (LGB) by a designated
      surgical team. Surgeon A operated as primary surgeon, with surgeon B assisting
      (Stage 1). Surgeon B learned LGB in stages: exposure and jejunojejunostomy (stage
      2), gastric pouch (stage 3), gastrojejunostomy (stage 4), and sequence all steps
      (stage 5). RESULTS: Surgeon A achieved confidence with LGB after 20 cases and
      surgeon B after 25 cases (stage 2), 18 cases (stage 3), 21 cases (stage 4), and
      16 cases (stage 5). Complications (8%) included small bowel obstruction (three);
      pulmonary embolus (two), and leak, stomal stenosis, and gastrogastric fistula
      (one each). There was a decreasing trend for operative duration, length of stay,
      and complications across the five stages (p < 0.05). CONCLUSIONS: By transferring
      skills in stages, a laparoscopic bariatric program can be established with
      minimal morbidity and mortality.

PMID- 15868263
TI  - Laparoscopic management for local recurrence of early gastric cancer after
      endoscopic mucosal resection.
AB  - Endoscopic mucosal resection (EMR) is a widely accepted technique for early
      gastric cancer because it is minimally invasive; however, incomplete resection
      with subsequent cancer recurrence in the remnant remains a difficult problem.
      Generally, the margins of the local recurrence lesions are unclear, and second
      EMR is difficult to perform because of scar formation after the first EMR. We
      performed a laparoscopic treatment on six patients with residual lesions after
      EMR and reviewed the safety and efficacy of this management. Laparoscopic
      management consisted of two techniques: laparoscopic wedge resection with a
      lesion-lifting method and laparoscopic-assisted distal gastrectomy with mini
      laparotomy. Cancerous lesions were completely resected with sufficient surgical
      margins circumferentially. Mean operative time was 171 min, mean estimated blood
      loss was 16.5 g, time to first walking was 1 day, duration of epidural analgesia
      was 2.2 days, and mean length of hospital stay was 13.5 days. There were no intra
      and postoperative complications, no conversion to open surgery, and no
      recurrence after surgery. No patients died of gastric cancer during a median
      follow-up of 60.3 months (range, 38-84). Laparoscopic management for residual
      lesions of early gastric cancer after EMR is a safe, effective, and minimally
      invasive procedure by which curative resection can be expected.

PMID- 15868264
TI  - Multimedia article. The keys to the new laparoscopic world Thumbs up! knot and
      Tornado knot.
AB  - Most laparoscopic surgeons feel some anxiety when performing intracorporeal
      knotting with conventional techniques [1, 2]. Two factors contribute to this
      anxiety. The first is the necessity of recognizing three dimensions on a two
      dimensional monitor. The conventional intracorporeal knotting techniques make
      loops by twisting the thread with a second pair of forceps. This necessitates
      cooperative movement of both hands, with the added difficulties of depth
      perception. Regular touch confirmations reduce problems with depth perception.
      However, touch confirmation is more complicated in laparoscopic surgery than in
      laparotomy. The second problem is that tied loops can come loose and escape the
      instruments, especially with hard thread. This is not only stressful but also
      increases operation time.

PMID- 15868265
TI  - Laparoscopic cholecystectomy for 58 end stage renal disease patients.
AB  - BACKGROUND: Since 1987, laparoscopic cholecystectomy (LC) has been widely used as
      the favored treatment for gallbladder lesions throughout the world. Because
      hemorrhage, infection, and delayed wound healing are the main causes of death
      after surgery for end-stage renal disease (ESRD), laparoscopic surgery is risky
      for ESRD patients. However, no information has been reported on such patients, so
      this study aimed to assess the safety of LC in ESRD patients. METHOD: From
      January 1994 to December 2003, the medical records of 58 ESRD patients under
      regular hemodialysis (HD) with gallbladder lesions undergoing LC were reviewed
      (ESRD-LC). The clinical features and outcomes of 6,182 patients with gallbladder
      lesions without ESRD undergoing LC were also summarized for comparison. RESULTS:
      Of 6,240 patients with gallbladder lesions undergoing LC, 58 (0.93%) had ESRD
      with regular HD. The ESRD-LC group clearly exhibited older age, higher frequency
      of associated disease, lower hemoglobin and platelet count, and elevated alkaline
      phosphatase, blood urea nitrogen, and creatinine values. However, only a higher
      frequency of high American Society of Anesthesiologists (ASA) grade and elevated
      creatinine value could differentiate ESRD-LC and LC patients by multivariate
      analysis. Similar blood loss, conversion rate, morbidity, mortality, and hospital
      stay were noted for the two groups. CONCLUSIONS: LC is safe for ESRD patients
      with gallbladder lesions. Only a higher frequency of high ASA grade and elevated
      creatinine value could differentiate ESRD-LC and LC patients. Similar blood loss,
      conversion rate, morbidity, mortality, and hospital stay were achieved by
      applying LC to treat ESRD patients. However, appropriate preoperative
      preparations and experienced operative techniques are still required to prevent
      mortality.

PMID- 15868266
TI  - The laparoscopic performance of novice surgical trainees: testing for
      acquisition, loss, and reacquisition of psychomotor skills.
AB  - BACKGROUND: It has been suggested that virtual reality (VR) might be useful for
      the selection of surgical trainees and the measurement of technical performance
      during preoperative training and retraining. This study was designed to determine
      whether it is possible to define and measure the acquisition, loss, and
      reacquisition of psychomotor skills in novice surgical trainees. METHODS: Novice
      surgical trainees (NSTs n = 10, junior surgical registrars with little or no
      prior experience with laparoscopic surgery) were tested and retested after 1
      month using the Minimally Invasive Surgical Trainer-Virtual Reality. Two tasks
      were used: the simple task [stretch diathermy (SD)] and the more complex task
      [manipulation diathermy (MD)]. The score was derived from the time taken to
      complete the task and the number of errors that occurred. Acquisition is the
      difference between the first and last score of the first training session, loss
      is the difference in score that occurs between the last score of the first
      training session and the first score of the second training session, and
      reacquisition is the difference in the first and last scores of the second
      training session. A performance criterion level was defined for each task by
      testing a group of experienced laparoscopic surgeons (n = 10). Groups were
      compared using the nonparametric Wilcoxon signed rank test, with p < 0.05
      considered to be significant. RESULTS: Acquisition of skill was found for five of
      10 NSTs with the SD task and 10/10 for the MD task. As a group the NSTs achieved
      the criterion level from the outset with the SD task and exceeded it by the
      eighth attempt for the MD task. The best score was achieved with fewer attempts
      during the second training session for the SD but not the MD task. The defined
      parameters are expressed as mean percentage score +/- SD for the 10 NSTs and for
      each task. There was a 36% (+/- 26) acquisition for the SD task compared with 50%
      (+/- 4) for the MD task (Wilcoxon p = 0.241). There was a 23% (+/- 19) loss for
      the SD task compared with 81% (+/- 16) for the MD task (p < 0.005). There was a
      20% (+/- 10) reacquisition for the SD task compared with 54% (+/- 7) for the MD
      task (p < 0.005). The mean scores were greater for the more complex task (MD),
      which was more useful in discriminating between the individual trainees and the
      two training sessions. CONCLUSIONS: It is possible to use VR to define the
      acquisition, loss, and reacquisition of psychomotor skills in individual NSTs and
      to compare them with a predefined performance criterion level. This study defines
      parameters that will be useful in repeated training sessions of NSTs in the
      preoperative phase of training and during retraining.

PMID- 15868267
TI  - Risk factors for conversion of laparoscopic cholecystectomy to open
      cholecystectomy.
AB  - BACKGROUND: Conversion to open cholecystectomy is still required in some
      patients. The aim of this study was to evaluate preoperative factors associated
      with conversion to open cholecystectomy in elective cholecystectomy and acute
      cholecystitis. METHODS: The records of 1,804 patients who underwent
      cholecystectomy from May 1992 to January 2004 were reviewed retrospectively. The
      demographics and preoperative data of patients who required conversion to
      laparotomy were compared to those with successful laparoscopic cholecystectomy.
      RESULTS: Conversion to open cholecystectomy was needed in 94 patients (5.2%),of
      which 44 (2.8%) had no inflammation and 50 (18.4%) had acute inflammation of the
      gallbladder. Male gender, age older than 60 years, previous upper abdominal
      surgery, diabetes, and severity of inflammation were all significantly correlated
      with an increased conversion rate to laparotomy. Also, the conversion from
      laparoscopic to open cholecystectomy in acute cholecystitis patients was
      associated with greater white blood cell count, fever, elevated total bilirubin,
      aspartate transaminase, and alanine transaminase levels, and the various types of
      inflammation. CONCLUSIONS: None of these risk factors were contraindications to
      laparoscopic cholecystectomy. This may help predict the difficulty of the
      procedure and permit the surgeon to better inform patients about the risk of
      conversion from laparoscopic to open cholecystectomy.

PMID- 15868268
TI  - Is laparoscopic appendectomy in children associated with an uncommon
      postoperative complication?
AB  - BACKGROUND: Laparoscopic appendectomy (LA) is controversial due to the high rate
      of intraabdominal abscess (IAA). We report a postlaparoscopic appendectomy
      complication (PLAC) observed in pediatric patients discharged after an uneventful
      postoperative period. METHODS: In this case series, a review of the medical
      records of children who underwent LA or open appendectomy (OA) during a 5-year
      period was performed. The diagnosis of PLAC was based on three well-defined
      criteria: time of appearance, clinical and laboratory findings, and
      ultrasonographic characteristic features. RESULTS: A total of 374 patients
      underwent appendectomy (LA, 129 patients; OA, 245 patients). One patient with
      conversion of LA to OA and 35 patients with gangrenous or perforated appendicitis
      (seven from the LA group and 28 from the OA group) were excluded from the study.
      After LA, nine children developed intraabdominal complications during their
      hospitalization (six infiltrate in the right lower quadrant and three IAA); these
      were also excluded. Discharge from the department was done when three conditions
      were fulfilled: normal body temperature, normal leukocyte count, and passage of a
      stool. Among the 112 LA patients, PLAC was observed in 15 (13.4%), aged 12.5 +/-
      2.9 years, who were discharged after LA in 2.7 +/- 0.9 days. Number of PLAC and
      time of its appearance were not significantly different in patients with normal
      or pathological appendix. Sonographic findings of PLAC at admission were fluid
      alone (n = 11), edematous mesenteric fat (n = 7), thickening of bowel wall (n =
      9), and more than one sign (n = 9). At repeated sonography, these signs were
      present in all patients, and IAA developed in one of them. All children were
      successfully treated with antibiotics for 10.1 +/- 3.9 days, one of whom
      underwent a CT-guided percutaneous drainage for IAA. CONCLUSIONS: PLAC may be the
      result of a slow development of local interstitial infection in the ileocecal
      area due to mesothelial damage caused by CO2 pneumoperitoneum and local thermal
      effect produced by energized systems. This may explain its delayed appearance and
      the efficacy of the antibiotic treatment.

PMID- 15868269
TI  - Intraabdominal adhesion formation of polypropylene mesh. Influence of coverage of
      omentum and polyglactin.
AB  - BACKGROUND: Adhesions after intraabdominal surgical procedures are related to
      high morbidity and mortality. Biomaterials, particularly those made of
      polypropylene, in the intraabdominal position have to be considered as
      pathophysiological cofactor in a multifactorial process of adhesion formation. To
      investigate the adhesive potential induced by the biomaterial, an animal model
      was performed. In addition, the influence of coverage by omentum or a polyglactin
      barrier was investigated. METHODS: In, 18 Chinchilla rabbits the biomaterial was
      placed laparoscopically using the intraperitoneal onlay mesh technique. Using
      this model, a polypropylene-polyglactin mesh compound (PPMC) was used with three
      different implantation techniques: group 1, PPMC implantation without coverage
      (PPMC): group 2, PPMC implantation with additional omentum coverage (PPMC-O): and
      group 3, PPMC implantation with coverage of an absorbable polyglactin mesh (PPMC
      V). The degree of adhesion formation was measured 90 days after implantation by
      computer-assisted planimetry. Morphometric examination followed the explantation
      analyzing the amount of foreign body response. RESULTS: We found a significant
      reduction of adhesion formation for the PPMC and PPMC-O groups compared to the
      PPMC-V group, in which dense adhesions were found. Morphometric investigations of
      the perifilamental granulomas of the pure (PPMC) group revealed a typical foreign
      body reaction with a mild to moderate fibrosis around all mesh fibers. However,
      tissue specimens of the PPMC-O and PPMC-V groups indicated a similar inflammatory
      reaction but significantly increased connective tissue formation around the
      polymer fibers compared to the pure PPMC group. CONCLUSION: The intraabdominal
      placement of a pure PPMC shows a neoperitonealization and perifilamental
      collagenous ingrowth with almost no adhesions. Coverage with omentum (PPMC-O) or
      polyglactin mesh (PPMC-V) resulted in a significant increase in inflammation and
      perifilamentary connective tissue formation.

PMID- 15868270
TI  - Mini-laparotomy and full laparotomy, but not laparoscopy, alter hepatic
      macrophage populations in a rat model.
AB  - BACKGROUND: Immune function is better preserved by laparoscopic versus
      conventional surgery. Numerous mediators of the systemic trauma response are
      synthesized and/or regulated by the liver. However, it has been stated that the
      advantages of laparoscopic surgery are no more obvious when conventional
      operations are performed via mini-laparotomy. We set out to compare the impact of
      laparoscopy and mini- and full laparotomy on the hepatic macrophage populations.
      METHODS: Male Lewis rats were subjected to anesthesia alone (control), mini
      laparotomy (1 cm), full laparotomy (7 cm), or laparoscopy for 60 min. Endpoints
      were the total protein in the peritoneal lavage fluid, hepatic ED-1 cells
      (recruited monocytes), hepatic ED-2 cells (Kupffer cells), the expression of OX-6
      in the liver, and C-reactive protein (CRP) in plasma. RESULTS: Protein in the
      peritoneal lavage fluid increased significantly after all interventions. Full
      laparotomy was accompanied by an enhancement in ED-1-positive monocytes in the
      liver parenchyma compared to all other groups (p < 0.001). Mini- and full
      laparotomy led to an increase in ED-2-positive Kupffer cells (p < 0.001).
      Laparoscopy did not affect the number of monocytes/macrophages. There was no
      significant alteration of OX-6 expression in either group. No change in the
      cellular composition in the periportal fields was observed. The CRP plasma levels
      did not significantly differ between groups. CONCLUSIONS: Laparoscopy completely
      prevents hepatic macrophage populations from expansion and normal cell
      disposition is preserved. Laparotomy, irrespective of incision size, increases
      the number of Kupffer cells. Moreover, full laparotomy, but not mini-laparotomy
      or laparoscopy, causes an increase in hepatic monocyte recruitment. The
      regulating pathways after surgery differ from other immunologic challenges, such
      as sepsis, in which immunocompetent cells accumulate and are stimulated in the
      periportal fields.

PMID- 15868271
TI  - Ergonomic testing of two different types of handles via virtual reality
      simulation.
AB  - BACKGROUND: Ergonomics in laparoscopic surgery is an unsolved problem.
      Deficiencies of the instrument handles are well-known and described in several
      reports and studies. Today, virtual training modules for laparoscopic surgery are
      available. The aim of this study was to evaluate the ability of a virtual reality
      (VR) simulator to determine the ergonomic properties of two different
      laparoscopic instrument handles. METHODS: Two different types of handles, a ring
      and an axial handle from Richard Wolf, were used to perform the short clip and
      cut task of the Xitact 500 LS simulator. The task was repeated every 2 days for a
      period of 5 weeks. After every trial the volunteers were asked structured
      questions about their preferences while using the two handles. RESULTS: The axial
      handle was superior or equal to the ring handle in all criteria. Learning curves
      over the entire time and day by day were similar. No differences were found for
      travel distances and error rates, but task times were different for both handles.
      The subjects preferred the axial handle at the end of the study. CONCLUSION: It
      is possible to determine differences in ergonomics of handle design with a VR
      trainer. In this study, the Richard Wolf axial handle was superior to the ring
      handle.

PMID- 15868272
TI  - Delivery of radiofrequency energy to the gastroesophageal junction (Stretta
      procedure) for the treatment of gastroesophageal reflux disease.
AB  - BACKGROUND: Radiofrequency (RF) energy treatment is increasingly offered before
      invasive surgical procedures for selected patients with gastroesophageal reflux
      disease (GERD). METHODS: Thirty-two patients undergoing the Stretta procedure
      were prospectively evaluated with upper endoscopy, manometry, 24-hour pH testing,
      SF-36 surveys, and GERD-specific questionnaires (GERD HRQL). RESULTS: Significant
      clinical improvement was observed in 91% of patients (29/32). Mean heartburn and
      GERD HRQL scores decreased (p = 0.001 and p = 0.003, respectively), and physical
      SF-36 increased (p = 0.05). At a minimum follow-up of 12 months, median
      esophageal acid exposure decreased (p = 0.79) and was normalized in eight
      patients. Median lower esophageal sphincter (LES) pressure was unchanged.
      Esophagitis healed in six of eight patients, but two patients with nonerosive
      disease developed asymptomatic grade A esophagitis during follow-up. At 12
      months, 56% of patients were off proton pump inhibits. Morbidity was minimal.
      CONCLUSIONS: RF delivery to LES is safe and significantly improves symptoms and
      quality of life in selected GERD patients.

PMID- 15868273
TI  - Fewer adhesions after laparoscopic surgery?

PMID- 15868274
TI  - Laparoscopic Roux-en-Y gastric bypass performed without staples.

PMID- 15868275
TI  - Outcome of laparoscopic redo fundoplication.

PMID- 15868276
TI  - Further modification of the dual-hemostat port closure technique.

PMID- 15868277
TI  - Low-grade B-cell MALT lymphoma of the stomach: a clinical challenge.

PMID- 15868278
TI  - Combined endoscopic treatment for cholelithiasis associated with
      choledocholithiasis.
AB  - BACKGROUND: The advent of endoscopic techniques changed surgery in many ways. For
      the management of cholelithiasis, laparoscopic cholecystectomy (LC) is the
      treatment of choice. This has created a dilemma in the management of
      choledocholithiasis. Today a number of option exist, including endoscopic
      sphinterotomy (ES) before LC in patients with suspected common bile duct (CBD)
      stones, laparoscopic bile duct exploration, open CBD exploration, and
      postoperative endoscopic retrograde cholangiopancreatography (ERCP). Also, the
      alternative technique of peroperative ES is emerging. METHODS: We report our
      experience of routine intraoperative cholangiography followed either by
      peroperative ERCP in one step or by transcystic drain and postoperative ERCP. In
      our technique, to facilitate Vater papilla cannulation we inserted a 450-cm
      transcystic guidewire that was caught by a duodenoscope. Papillotome was then
      inserted over the guidewire to ensure cannulation of the CBD. RESULTS: Twenty
      eight patients were treated successfully in one step and 24 in two steps. The
      mean operative time was 181 +/- 41 min for patients treated in one step and 131
      +/- 30 min for patients treated in two steps. The mean hospital stay was 4.8 +/-
      3.3 days for patients treated in one step and 9.6 +/- 4.0 days for patients
      treated in two steps. Five patients (18%) with positive intraoperative
      cholangiography for stones for whom peroperative ERCP was not available showed a
      normal postoperative transcystic cholangiogram and therefore ERCP was canceled.
      Fourteen of 25 patients treated in one step and none of 17 treated in two steps
      had raised serum amylase, which resolved spontaneously with no symptoms. No
      patient developed postoperative pancreatitis. Three (10%) ERCP complications were
      observed, consisting of mild bleeding of the papilla. All cases were managed by
      endoscopic adrenaline injection. There was no mortality. CONCLUSION: We believe
      peroperative ERCP with the technique described should be considered as the
      treatment of choice for choledocholithiasis associated with cholelithiasis. When
      single-stage treatment is not possible, a two-step rendezvous technique should be
      preferred.

PMID- 15868279
TI  - Towards standardization of dual X-ray absorptiometry (DXA) at the forearm: a
      common region of interest (ROI) improves the comparability among DXA devices.
AB  - Manufacturer-implemented regions of interest (ROIs) to determine the bone mineral
      density (BMD) at the forearm are currently not standardized across dual X-ray
      absorptiometry (DXA) devices. We hypothesized that their differences introduce
      considerable variation in measurement results for forearm BMD when taken on
      different devices, and that a ROIs common to all devices with standardized
      placement and size significantly improve device comparability. The common ROI was
      defined to have a fixed length of 2 cm and to extend proximally from the location
      where the ulna and radius bones superimpose on the DXA image. The effects of
      universal standardization of forearm BMD were combined with and compared to those
      of the common ROI. They were drawn on 91 female study participants (ages 20-80
      years, 10 per decade) who were scanned on Hologic QDR-4500, Aloka DCS-600EX, GE
      Lunar PIXI and Norland pDEXA DXA scanners. For all device combinations,
      manufacturer-implemented ROI root mean-square errors were significantly higher
      than for the common ROI, suggesting that implementing an ROI with common design
      on all scanners is a good way to reduce interdevice variability. When
      manufacturer-implemented ROIs were universally standardized root mean-square
      error (RMSE) values were less different from that of the nonstandardized Common
      ROI, suggesting that universal standardization can further improve interdevice
      comparability even when a common ROI such as the one implemented here is used.
      ROI standardization dramatically improves interdevice comparability.

PMID- 15868280
TI  - Plasma concentrations of 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D are
      related to the phenotype of Gc (vitamin D-binding protein): a cross-sectional
      study on 595 early postmenopausal women.
AB  - The major transporter of vitamin D metabolites in the circulation is the
      multifunctional plasma protein Gc, also known as group-specific component, Gc
      globulin, vitamin D-binding protein, or DBP. There are several phenotypes of Gc,
      and we examined the influence of Gc phenotype and Gc concentration on vitamin D
      status. By using isoelectric focusing we identified the Gc phenotype of 595
      caucasian recent postmenopausal women enrolled into the Danish Osteoporosis
      Prevention Study (DOPS). We measured plasma concentration of Gc by
      immunonephelometry (coefficient of variation [CV] < 5%), 25-hydroxy vitamin D
      (25OHD) by a competitive protein-binding assay (CV 10%), and 1,25-dihydroxy
      vitamin D (1,25(OH)(2)D) by a radioimmunoassay (CV 6--14%), and calculated index
      as the molar ratio of vitamin concentration divided by Gc concentration. Plasma
      levels of Gc, 25OHD, 25OHD index, and 1,25(OH)(2)D, but not 1,25(OH)(2)D index,
      differed significantly between women with different Gc phenotype, being highest
      in Gc1-1, intermediate in Gc1-2, and lowest in Gc2-2. In multiple regression
      analysis, Gc concentration was an independent predictor of 1,25(OH)(2)D, whereas
      Gc phenotype was a significant predictor of 25OHD concentration, even after
      adjustment for the effects of season, sunbathing habits, skin thickness, use of
      vitamin supplements, smoking, and body mass index (BMI). Plasma parathyroid
      hormone (PTH) level did not differ between Gc phenotypes. Despite the fact that
      more than 60% of the women with Gc phenotype Gc2-2 had plasma 25OHD levels of
      less than 50 nmol/L none of them had plasma PTH higher than reference limits.
      Bone mineral content (BMC), Bone mineral density (BMD), and bone markers did not
      differ between Gc phenotypes. In conclusion, plasma 1,25(OH)(2)D, 25OHD, and
      25OHD index are related to Gc phenotype, and we speculate that the thresholds for
      vitamin D sufficiency differ between Gc phenotypes.

PMID- 15868281
TI  - Localization of matrix metalloproteinases, (MMPs) their tissue inhibitors, and
      vascular endothelial growth factor (VEGF) in growth plates of children and
      adolescents indicates a role for MMPs in human postnatal growth and skeletal
      maturation.
AB  - Numerous studies have focused on the expression, regulation, and biological
      significance of matrix metalloproteinases (MMPs) in the growth plate. Findings in
      mouse knockout models and in vitro data from various species indicate that MMPs
      not only degrade extracellular matrix components but may regulate the activity of
      local growth factors. In this study we investigated the presence, distribution,
      and activity of various MMPs and inhibitors, tissue transglutaminase (tTG or TG2)
      and vascular endothelial growth factor (VEGF) in the human child and adolescent
      growth plates by means of immunohistochemistry and gelatin zymography. Tissue was
      derived during orthopedic surgery (epiphysiodesis) in two prepubertal and four
      pubertal patients.MMP-2 and MMP-14 were present in reserve cell chondrocytes. MMP
      14 was the most prominent MMP within all zones of the growth plate including
      proliferating chondrocytes. MMP-1 and MMP-13 (collagenases 1 and 3), MMP-9
      (gelatinases B), MMP-10, and MMP-11 (stromelysins) and VEGF were positive in
      hypertrophic chondrocytes and osteoblasts. MMP-2 showed the same expression
      pattern but was negative in osteoblasts. Osteoclasts stained positive for MMP-9,
      MMP-2, and TG2. Tissue inhibitor of MMP (TIMP)-1 was present in all zones of the
      growth plate, osteoblasts, and osteoclasts; TIMP-2 was found in hypertrophic
      chondrocytes and osteoblasts. In summary, the presence of MMPs, TIMPs, TG2, and
      VEGF in our study indicated that the MMPs are relevant in growth plate physiology
      during the postnatal period in humans. The specific location of MMP expression
      within the growth plate may be the basis for further studies on the role of MMPs
      in the local regulation of chondrocyte differentiation, proliferation, and
      ossification at the chondroosseus junction.

PMID- 15868283
TI  - Expression of PPARgamma and beta/delta in human primary osteoblastic cells:
      influence of polyunsaturated fatty acids.
AB  - As previously reported, the age-related association between bone loss and
      increased marrow adipose volume may involve inhibitory effects of polyunsaturated
      fatty acids (PUFAs) potentially released by medullary adipocytes on osteoblastic
      proliferation and cell cycle progression. Because PUFAs have been reported to
      activate peroxisome proliferator-activated receptors (PPARs), we investigated the
      expression of these nuclear receptors in human primary osteoblastic (hOB) cells
      and examined the effects of natural PPAR ligands on hOB cell proliferation. We
      demonstrated basic expressions of PPARgamma and PPARbeta/delta in hOB cells at
      the protein level. As already shown for PUFAs, a short-term treatment with
      15deoxy-Delta(12,14) -prostaglandin J2 (15dPGJ2) or prostacyclin (PGI2), which
      are specific ligands for PPARgamma and PPARbeta/delta, respectively, also
      significantly inhibited hOB cell proliferation. Given that the cell cycle
      withdrawal resulting from PPARgamma activation was often associated with the
      induction of cell differentiation, long-term effects of PUFAs and 15dPGJ2 were
      also assessed on the expression levels of transcription factors. PUFAs and
      15dPGJ2 enhanced the expression of PPARgamma in hOB cells. It is of interest to
      note that PPARgamma protein level was dose-dependently increased, whereas that of
      Cbfal was decreased by a fatty acid-rich serum. In conclusion, this study shows
      that PPARgamma and beta/delta are expressed by hOB cells. The results further
      suggest that the short-term antiproliferative effect of PUFAs may involve PPAR
      activation in hOB cells, resulting in a cell cycle withdrawal favorable for the
      long-term differentiating effects of fatty acids. Further studies are now
      required to confirm the functional role of PPARs in the antiproliferative effects
      of PUFAs in hOB cells.

PMID- 15868282
TI  - Quantification of trabecular bone structure using magnetic resonance imaging at 3
      Tesla--calibration studies using microcomputed tomography as a standard of
      reference.
AB  - The purpose of this study is to use high-resolution magnetic resonance (MR)
      imaging at 3 Tesla (3T) to quantify trabecular bone structure in vitro using
      femoral head specimens, and to correlate the calculated structure measures with
      those that were determined using microcomputed tomography (microCT), the standard
      of reference. Fifteen cylindrical cores were obtained from fresh femoral heads
      after total hip arthroplasty. MR images were obtained at 3T using a transmit
      receive wrist coil. High-resolution coronal images were acquired using a modified
      three-dimensional (3D) fast-gradient echo sequence. From these data sets two
      dimensional (2D) structural parameters analogous to bone histomorphometry were
      derived by using both mean intercept length (MIL) methods based on the plate
      model and the more recent model-assumption free 3D distance-transformation (DT)
      methods. The parameters measured by the 2D plate model-based MIL method and the
      DT method included apparent (App). BV/TV (bone volume/total volume), App. Tb.Th
      (trabecular thickness), App. Tb.Sp (trabecular separation), and App. Tb.N
      (trabecular number). Identical regions of interest were analyzed in the MR images
      and the microCT data sets, and similar structure measures were derived. The means
      and standard deviations of the parameters over all slices were calculated and MR
      derived measures were correlated with those derived from the microCT data sets
      using linear regression analyses. Structure measures were overestimated with MRI,
      for example, the mean App. BV/TV was 0.45 for MRI and 0.20 for microT, and the
      slope of the graph was 1.45. App. Tb.Th was overestimated by a factor of 1.9,
      whereas App. Tb.Sp was underestimated; Tb.N showed the smallest effect.
      Correlations between the individual parameters were excellent (App. BV/TV, r2 =
      0.82; App. Tb.Sp, r2 = 0.84; App. Tb.N, r2 = 0.81), except for App.Tb.Th (r2 =
      0.67). The results of this study show that trabecular bone structure measures may
      be obtained using 3T MR imaging. These measures, although higher than the
      standard of reference, show a highly significant correlation with true structure
      measures obtained by microCT.

PMID- 15868284
TI  - Impact of melanoma diagnosis on sun-awareness and protection: efficacy of
      education campaigns in a high-risk population.
AB  - BACKGROUND: Malignant melanoma is a significant cause of morbidity and mortality
      worldwide. Sun-awareness campaigns increase public knowledge but may not
      translate into behavioral changes in practice, which is particularly alarming
      when reported for individuals in high-risk groups. In particular, patients
      diagnosed with melanoma are at increased risk of developing subsequent primary
      melanomas compared with the general population. OBJECTIVES: The study was
      undertaken (1) to assess whether patients with known risk factors for developing
      melanoma had been exposed to preventative campaign messages prior to their
      diagnosis, (2) to quantify whether the diagnosis of melanoma changed sun-related
      attitudes and behavior, and (3) to assess the adequacy of sun-related advice
      given to patients with melanoma, as well as their compliance with the advice.
      METHODS: Using an anonymous questionnaire, 217 patients previously diagnosed with
      melanoma were interviewed on the source and frequency of received sun-related
      advice, as well as on their knowledge, attitudes, and behavior toward sun
      protection before and after the diagnosis. RESULTS: The number of patients who
      reported receiving sun-related advice after being diagnosed with melanoma
      increased by 36% (52% pre-vs. 88% postDiagnosis), with advice being given more
      frequently and more often by a physician (19% pre- vs. 49% postdiagnosis).
      Furthermore, sun-related attitudes and behavioral practices were positively
      altered. Yet, patients with known risk factors were not preferentially targeted
      for advice before their diagnosis. CONCLUSIONS: The diagnosis of melanoma leads
      to increased sun-awareness and protection. While dermatologists should continue
      their efforts to promote and reinforce sun-awareness in patients with melanoma,
      additional emphasis on preventative targeting of high-risk individuals would be
      of marked benefit in decreasing the overall incidence of melanoma. Non
      dermatologists, such as family physicians, can be key players in this
      preventative campaign, and can be educated to recognize and educate patients at
      risk, as well as direct them to be followed under dermatology care.

PMID- 15868310
TI  - Stephen Rothman's text on physiology and biochemistry of the skin.
AB  - BACKGROUND: Forty-nine years ago the first complete and authoritative English
      text on the physiology and biochemistry of the skin was published by Stephen
      Rothman, an early basic researcher in dermatology. OBJECTIVE: The purpose of the
      article is to learn more about Stephen Rothman and his 1954 text, to learn more
      about what was known and not known then, to learn more about what was considered
      significant, and to learn more about what was popular at that time. CONCLUSION:
      Considering the techniques available and the knowledge base, Rothman's 1954 text
      shows that basic dermatology research 50 years ago had developed to a reasonably
      sophisticated degree.

PMID- 15868311
TI  - Integrating biologic agents into management of moderate-to-severe psoriasis: a
      consensus of the Canadian Psoriasis Expert Panel. February 27, 2004.
AB  - BACKGROUND: Approximately 2% of people worldwide have psoriasis, with as many as
      1 million people with psoriasis in Canada alone.1,2 The severity of psoriasis
      ranges from mild to severe. It can lead to substantial morbidity and
      psychological stress and have a profound negative impact on patient quality of
      life.3,4 Although available therapies reduce therapies reduce the extent and
      severity of the disease and improve quality of life,3 reports have indicated a
      patient preference for more aggressive therapy and a dissatisfaction with the
      effectiveness of current treatment options.5 OBJECTIVE: A Canadian Expert Panel,
      comprising Canadian dermatologists, convened in Toronto on 27 February 2004 to
      reach a consensus on unmet needs of patients treated with current therapies and
      how to include the pending biologic agents in and improve the current treatment
      algorithm for moderate-to-severe psoriasis. Current treatment recommendations
      suggest a stepwise strategy starting with topical agents followed by phototherapy
      and then systemic agents.3,6,7 The Panel evaluated the appropriate positioning of
      the biologic agents, once approved by Health Canada, for the treatment of
      moderate-to-severe psoriasis. METHODS: The Panel reviewed available evidence and
      quality of these data on current therapies and from randomized, controlled
      clinical trials.8-14 Subsequently, consensus was achieved by small-group
      workshops followed by plenary discussion. RESULTS: The Panel determined that
      biologic agents are an important addition to therapies currently available for
      moderate-to-severe psoriasis and proposed an alternative treatment algorithm to
      the current step wise paradigm. CONCLUSION: The Panel recommended a new treatment
      algorithm for moderate-to-severe psoriasis whereby all appropriate treatment
      options, including biologic agents, are considered together and patients'
      specific characteristics and needs are taken into account when selecting the most
      appropriate treatment option.

PMID- 15868312
TI  - Patient satisfaction with psoriasis therapies: an update and introduction to
      biologic therapy.
AB  - BACKGROUND: Psoriasis is a chronic, immune-mediated skin condition that often
      requires lifelong treatment. Many patients report dissatisfaction with
      traditional nonbiologic therapies because they are ineffective for their
      psoriasis, are associated with side effects, or impact negatively on quality of
      life. OBJECTIVES: The aim of this article is to review the effect on patient
      quality of life of traditional nonbiologic psoriasis therapies and to discuss the
      impact of biologic psoriasis therapies on patient satisfaction. METHODS: A review
      of the literature is presented. RESULTS: Traditional nonbiologic psoriasis
      therapies can negatively impact quality of life due to a variety of factors
      including inconvenience and toxicity. Biologic agents have been developed that
      target the immunopathogenesis of psoriasis. Based on favorable efficacy and
      safety results in clinical trials, some of these agents are now approved for
      clinical use. Evidence suggests that patients receiving biologic therapies
      experience significant improvements in health-related quality of life.
      CONCLUSION: Biologic agents offer new hope for patients with psoriasis that their
      chronic condition can be controlled in a manner that improves their quality of
      life and may lead to high levels of satisfaction with their treatment.

PMID- 15868313
TI  - Segmental neurofibromatosis follows blaschko's lines or dermatomes depending on
      the cell line affected: case report and literature review.
AB  - BACKGROUND: Segmental neurofibromatosis type 1 (NF-1) has the characteristic
      features of generalized NF-1 but is isolated to a particular segment of the body.
      Segmental NF-1 results from a postzygotic mutation during embryogenesis in the NF
      1 gene on chromosome 17. The embryologic timing of the mutation and cell types
      affected predict the clinical phenotype. OBJECTIVE: We present a case of a 52
      year-old woman with segmental neurofibromas isolated to the right cheek and neck.
      We review the recent literature on the genetic and cellular differences between
      the various clinical manifestations of segmental NF-1. METHODS: A MEDLINE search
      for cases of segmental neurofibromatosis was conducted. RESULTS: In patients with
      segmental NF-1 presenting as neurofibromas-only, the distribution follows a
      neural distribution in dermatomes because the genetic mutation appears to be
      limited to Schwann cells. In patients with pigmentary changes only, the NF-1
      mutation has been shown to occur in fibroblasts and the distribution tends to
      follow the lines of Blaschko. CONCLUSION: Our patient's neurofibromas were
      secondary to a postzygotic mutation in the NF-1 gene of neural crest-derived
      cells. This mutation most likely occurred later in embryogenesis in cells that
      had already differentiated to Schwann cells and were committed to the dermatomal
      distribution of the right neck and cheek region (C2).

PMID- 15868314
TI  - Viral and nonviral uses of imiquimod: a review.
AB  - BACKGROUND: Imiquimod is a topical immunomodulator that is indicated for the
      treatment of external genital and perianal warts. This drug has been recently
      approved for the treatment of actinic keratoses and superficial basal cell
      carcinoma. There is a growing body of evidence for its effectiveness in treating
      a variety of other skin conditions. OBJECTIVE: This review examines the role of
      imiquimod 5% cream in the treatment of skin diseases such as actinic keratoses,
      basal cell carcinoma, Bowen's disease, lentigo maligna, and extramammary Paget's
      disease. METHODS: Published literature containing the words "Imiquimod" or
      "Aldara" was reviewed and summarized. RESULTS: This agent has demonstrated
      indirect antiviral and antitumor effects in animal models. Although the exact
      mechanism of action is unknown, imiquimod is an agonist for toll-like receptor
      (TLR) 7 and is thought to act by inducing cytokines, such as interferon alpha
      (IFN-alpha), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNF-alpha).
      These cytokines trigger the immune system to recognize the presence of a viral
      infection or tumor and the associated lesion is ultimately eradicated. Side
      effects are generally well tolerated with local skin reactions reported most
      frequently. CONCLUSION: Imiquimod has been shown to be a safe and effective
      treatment for a variety of skin conditions.

PMID- 15868315
TI  - Epidermodysplasia verruciformis in two half brothers with HIV infection.
AB  - BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare disorder characterized
      by widespread flat and common verrucae. From 25% to 50% of EV cases are
      inherited, usually with an autosomal recessive pattern. An X-linked inheritance
      has also been reported. Many EV patients have a cellular immunity defect. HIV
      associated lesions have been found to contain HPV-5, HPV-8, and HPV-20.
      OBJECTIVE: We describe two HIV-positive Hispanic maternal half brothers who
      presented with asymptomatic polyangular papules and plaques on the face, trunk,
      and extremities and which first appeared 4-5 years prior. The histopathology is
      consistent with EV. HPV-8 was detected by in situ hybridization. The patients
      were treated with topical imiquimod for two months without improvement.
      CONCLUSION: To our knowledge, this is the first reported case of
      epidermodysplasia verruciformis in HIV-positive pediatric patients.

PMID- 15868316
TI  - Ductal anatomy: a determinant of successful stenting in hypoplastic left heart
      syndrome.
AB  - Interventional palliation for hypoplastic left heart syndrome (HLHS) could reduce
      the current morbidity and mortality. Stenting of the arterial duct is the
      critical interventional step for HLHS. We reviewed our experience with 40
      consecutive patients with HLHS referred for stenting of the ductus arterious
      (DA). Thirty-nine of 40 (97%) infants had suitable anatomy and were successfully
      stented. The infants were grouped by orientation of the ductus in the frontal
      plane. Type 1 DA anatomy had a leftward loop at a mean orientation of 18 degrees
      from the vertical plane. Type 2 ductal anatomy was mesoverted, with a mean
      orientation of 7.1 degrees from the vertical plane. Type 3 ductal anatomy
      displayed a rightward axis, with a mean of -4 degrees rightward. Orientation of
      the DA was significantly related to length of the ductus, number of stents
      required for complete coverage, and technical and procedural complications. Type
      1 DA occurred in 65% of patients, and there was 100% technical success, no
      mortality, and only an 8% incidence of complications. Type 2 anatomy occurred in
      27% of patients and there was 100% success. However, the technical and procedural
      complications increased to approximately 50%. Type 3 ductal anatomy was seen in
      only 3 patients, 2 of whom were successfully stented. There was no procedural
      related mortality, and all stented patients were weaned from prostaglandin. There
      were only two late complications (coarctation). We conclude that ductal stenting
      using self-expanding nitinol stents is successful in more than 95% of infants
      with HLHS. Patients with HLHS and favorable ductal anatomy should be considered
      for primary ductal stenting.

PMID- 15868317
TI  - Interventions in Kawasaki disease.
AB  - During the past 10 years, the clinical experience of catheter interventional
      treatment in Kawasaki disease has gradually increased. These treatments include
      balloon angioplasty, stent implantation, rotational ablation, and transluminal
      coronary revascularization. Because coronary artery stenosis in Kawasaki disease
      commonly involves severe calcification, in contrast with adult atherosclerotic
      coronary artery lesions, the indication or technique of catheter intervention for
      adult patients cannot be directly determined. Satisfactory acute results for
      coronary balloon angioplasty were obtained in patients in a relatively short
      interval from the onset of disease, especially within 6 years. However, the
      incidence of restenosis after angioplasty was still high. Rotational ablation may
      be the most appropriate catheter intervention for Kawasaki disease. The advantage
      of rotational ablation is the high success rate, even in patients with calcified
      coronary artery stenosis. Stent implantation requires larger arterial access and
      is not possible in younger children. Care should be paid to the detection of new
      aneurysm formation because this was associated with the use of additional balloon
      angioplasty using high-pressure balloon inflation. Anticoagulation or
      antiplatelet regimens are essential for long-term management.

PMID- 15868318
TI  - Transcatheter aortic valve implantation and mitral valve repair: state of the
      art.
AB  - Surgical replacement of cardiac valves evolved significantly since its first use.
      Evolution of techniques and valves used was driven by the frequent complications
      encountered with surgically implanted valves. Transcatheter implantation of
      valves is a new technique which continues to be under investigation and promises
      to perform a task with less risk and potentially better outcome. In addition, new
      techniques are being developed to address minimizing mitral regurgitation.
      Progress in transcatheter valve implantation and catheter mitral annuloplasty is
      reviewed in this article.

PMID- 15868320
TI  - Is routine cardiac catheterization necessary in the management of patients with
      single ventricles across staged Fontan reconstruction? No!
AB  - With the advent of cardiac magnetic resonance imaging and high-resolution
      echocardiography, cardiac catheterization is unnecessary in clinical protocols in
      the "routine" single ventricle patient. Catheterization adds little to clinical
      care in these cases, and there are significant risks and costs associated with
      it. Catheterization should be reserved for cases in which noninvasive evaluations
      are equivocal, conflictory, demonstrate deterioration, or needed for
      intervention. This article delineates the role of noninvasive evaluations
      relative to cardiac catheterization in the routine single ventricle patient.

PMID- 15868319
TI  - Percutaneous interventions on severe coarctation of the aorta: a 21-year
      experience.
AB  - Different percutaneous interventions can be used to treat coarctation of the
      aorta. However, a great amount of information is still needed regarding the long
      term course. This article reviews our experience spanning 21 years in the
      percutaneous treatment of aortic coarctation. Four different conditions for
      treatment were considered. The first condition 1 (group 1) was balloon
      angioplasty in neonates and infants with untractable heart failure (n = 54; mean
      age, 1.2 +/- 1.4 months). After balloon angioplasty, most infants sustained
      significant clinical improvement. However, 9 patients died in the hospital (17%).
      As a result, we monitored the course of the 45 survivors during a mean period of
      10 +/- 6 years (range, 1-19). During this follow-up period, 17 patients needed a
      single additional intervention on coarctation (8 underwent surgery and 9 were
      treated percutaneously). After this second treatment, 11 patients needed one or
      more further interventions. The actuarial survival probability was 83% at 19
      years, with 43% of patients remaining surgery free and 23% reintervention free.
      The second condition (group 2) was balloon angioplasty in children and adults
      with coarctation of the aorta before the stenting era (n = 28; mean age, 13 +/- 8
      years). After treatment, serial hemodynamic and angiographic studies were
      performed. The long-term relief was higher in patients with a discrete type of
      coarctation. The rate of late aneurysm formation was 6%. The third condition
      (group 3) was stent palliation in infants and children younger than the age of 6
      years (n = 17; mean age, 2.1 +/- 1.7 years). The stent was implanted for
      nondilatable stenoses, as a nondefinitive procedure. Stent palliation provides
      complete initial relief in hypoplastic coarctations or life-threatening
      conditions. However, further stent expansion is required to ensure adequate stent
      diameter in the growing aortic wall. In addition, late intrastent proliferation
      may occur in small stent diameters (18%) and aneurysm formation in hypoplastic
      coarctations (18%). Both late complications can be managed percutaneously. The
      fourth condition (group 4) was stent repair of severe aortic coarctation in
      adults, adolescents, and children older than the age of 6 years (n = 73; mean
      age, 20 +/- 12 years). Significant relief was observed after treatment, which
      persisted at follow-up. One patient died at treatment (1.3%). After a mean follow
      up of 5 +/- 3 years, all 72 patients remained symptom free and no restenosis or
      late aneurysm were detected.

PMID- 15868321
TI  - Challenges encountered during closure of atrial septal defects.
AB  - Since the introduction of transcatheter interventional occlusion of atrial septal
      defects (ASDs) by King and coworkers, the device closure has become the standard
      treatment of selected atrial defects. Although it has become routine for standard
      clinical practice, increasing knowledge of intracardiac anatomy, modification of
      implantation techniques, and improvements in device designs are making this
      treatment modality increasingly applicable to a wider range of selected patients.
      This report summarizes the current trends in patient selection, focusing on the
      anatomical limits of applicability for ASD device closure, and discusses the
      future possibilities. Furthermore, typical complications are described with
      regard to the rare erosion of the atrial roof or the aortic root. Current
      practice is to oversize the device if the anterior rim toward the aorta tends to
      be diminutive, achieving a secure position of the device around the aortic root.
      This and the shape memory of the device may play a major role in this serious
      complication and should be reconsidered. Although most interventional occlusions
      of interatrial defects with a device have become clinically routine, some
      situations remain highly challenging.

PMID- 15868322
TI  - Echocardiographic guidance of catheter-based treatments of atrial septal defect:
      transesophageal echocardiography remains the gold standard.
AB  - The availability of echocardiographic imaging to the catheterization laboratory
      has been recognized as an essential component of every congenital heart program
      for almost 30 years. The imaging data that are uniquely available using this
      technique may be used to plan the catheterization procedure; to add insights
      regarding valve anatomy and chordal insertions and myocardial performance; to
      assist in the identification of pericardial effusions; and to provide additional
      guidance for the performance of pericardiocentesis.

PMID- 15868323
TI  - Multicenter experience with perventricular device closure of muscular ventricular
      septal defects.
AB  - Hybrid procedures are becoming increasingly important, especially in the
      management of congenital heart lesions for which there are no ideal surgical or
      interventional options. This report describes a multicenter experience with
      perventricular muscular venticular septal defect (VSD) device closure. Three
      groups of patients (n = 12) were identified: infants with isolated muscular VSDs
      (n = 2), neonates with aortic coarctation and muscular VSDs (n = 3) or patients
      with muscular VSDs and other complex cardiac lesions (n = 2), and patients with
      muscular VSDs and pulmonary artery bands (n = 5). Via a sternotomy or a
      subxyphoid approach, the right ventricle (RV) free wall was punctured under
      transesophageal echocardiography guidance. A guidewire was introduced across the
      largest defect. A short delivery sheath was positioned in the left ventricle
      cavity. An Amplatzer muscular VSD occluding device was deployed across the VSD.
      Cardiopulmonary bypass was needed only for repair of concomitant lesions, such as
      double-outlet right ventricle, aortic coarctation, or pulmonary artery band
      removal. No complications were encountered using this technique. Discharge
      echocardiograms showed either mild or no significant shunting across the
      ventricular septum. At a median follow-up of 12 months, all patients were
      asymptomatic and 2 patients had mild residual ventricular level shunts.
      Perventricular closure of muscular VSDs is safe and effective for a variety of
      patients with muscular VSDs.

PMID- 15868324
TI  - Cardiac catheterization is necessary before bidirectional Glenn and Fontan
      procedures in single ventricle physiology.
AB  - There are significant mortality and morbidity in bidirectional Glenn (stage II)
      and Fontan (stage III) procedures for congenital heart diseases with single
      ventricle physiology. In order to minimize the mortality and morbidity, the
      presence or absence of hemodynamic and anatomical abnormalities, such as poor
      ventricular function, coarctation of the aorta, pulmonary artery distortion, high
      pulmonary resistance, and abnormal collateral vessels, should be evaluated.
      Echocardiography and magnetic resonance imaging (MRI) can visualize ventricular
      size and coarctation of the aorta but may fail to visualize pulmonary artery
      distortion. Furthermore, cardiac catheterization is needed to measure pulmonary
      resistance. If the pulmonary resistance is > 3 Wood units/m2 before stage II, the
      risk for the bidirectional Glenn operation may be high. Abnormal aortopulmonary
      collateral vessels may develop after the stage II procedure and echocardiography
      and MRI may not visualize these vessels. Coil embolization may be required to
      treat these vessels. In conclusion, cardiac catheterization is required to
      evaluate abnormalities, which may be treated by interventional catheterization,
      and to reduce mortality and morbidity of stage II and III procedures.

PMID- 15868325
TI  - Vascular access and management of its complications.
AB  - Vascular access is needed to realize the potential of therapeutic cardiac
      catheterization and may consume up to 25% of the entire procedure time. Repeat
      interventions and multiple cardiac surgeries may result in incremental loss of
      access sites. The following article discusses general aspects of vascular access,
      imaging tools to facilitate access, the various access sites with technical
      approach, advantages, and specific complications. Strategies for vessel
      protection and management of acute bleeding and iatrogenic fistulas are
      presented. Also, strategies for vessel restoration after acute and chronic
      vascular occlusion are reviewed.

PMID- 15868326
TI  - Creation and enlargement of atrial defects in congenital heart disease.
AB  - Transcatheter creation and enlargement of interatrial defects (IAD) may improve
      hemodynamics; however, procedural outcomes have not been well defined. Hospital
      records were reviewed for children who underwent percutaneous procedures to
      create and enlarge an IAD and were grouped as follows: (1) right and (2) left
      heart obstructive lesions, (3) left atrial (LA) decompression during left heart
      assist, (4) failing Fontan circulation, and (5) miscellaneous. Forty-five
      children (mean age, 3.4 +/- 4.7 years; 30 (67%) male) were identified. In group 1
      (n = 6), all achieved endpoints of right atrial (RA) decompression (n = 2),
      improved left ventricular filling (n = 3), or improved arterial saturations (n =
      1). In group 2 (n = 18), mean LA pressure decreased (21 +/- 6 to 13 +/- 5 mmHg, p
      < 0.001) and arterial saturations increased (61 +/- 13% to 78 +/- 11%, p <
      0.001). All except 2 patients achieved definitive repair, further palliation (n =
      9), or heart transplantation (HTX) (n = 7). In group 3 (n = 5), the LA was
      decompressed (21 to 13 mmHg, p = 0.03) in all, and all except 1 patient survived
      to HTX (n = 2) or full recovery (n = 2). In group 4 (n = 11), of 7 patients with
      a low cardiac output syndrome after surgery, despite improved atrial shunting, 3
      died and 1 required a HTX. In group 5 (n = 5), RA decompression (n = 1) or
      improved arterial saturation (n = 4) was achieved in all. Overall, 5-year HTX
      free survival was 75%. Mechanical ventilation before the procedure (p < 0.001),
      the need for a blade septostomy (p = 0.002), and higher LA pressures after the
      procedure (p = 0.04) independently predicted mortality or the requirement for
      HTX. Transcatheter optimization of an atrial communication can help optimize
      treatment strategies and has a low procedural risk.

PMID- 15868327
TI  - Echocardiographic guidance of transcatheter closure of atrial septal defects: is
      intracardiac echocardiography better than transesophageal echocardiography?
AB  - Transcatheter closure of atrial septal defects is an established practice. The
      imaging method best suited for guidance of this procedure is under debate. This
      review highlights the areas of disagreement and presents available evidence
      supporting the contention that intracardiac echocardiography is at least as good,
      if not a superior imaging method to guide the procedure. Points of discussion
      include comparisons of imaging capability, complications or discomfort, and the
      relative costs of these procedures. It is concluded that intracardiac
      echocardiography is the superior imaging method.

PMID- 15868330
TI  - [Glucocorticoid therapy in the course of time].

PMID- 15868331
TI  - [Prescription of glucocorticoids by rheumatologists in patients with rheumatoid
      arthritis in Germany].
AB  - Systemic GCs are among the most important therapeutic options in modern
      rheumatology. Due to their fast clinical effects and their high anti-inflammatory
      potential, they are indispensable in a large number of cases. This applies
      despite the well-known spectrum of adverse events and despite limited evidence
      from randomized clinical trials. In this situation, the results of observational
      studies gain additional importance. They provide information on therapeutic
      decisions of rheumatologists concerning GC therapy and their combination with
      other drugs as well as concerning the prevention of adverse events such as GC
      induced osteoporosis. The data gathered in the national database of the German
      Collaborative Arthritis Centers show that at the time of documentation 60% of all
      RA patients were under therapy with GCs, 85% of these were treated with a dosage
      of up to 7.5 mg/d. GCs are especially frequently used in combination with new or
      highly potent DMARDs. This underlines that rheumatologists take activity and
      severity into account in deciding both about GCs and DMARDs. However, there is
      high practice variation regarding the frequency of GC use among the
      rheumatological facilities which demonstrates the lack of good
      evidence.Rheumatologists are aware of various patient risks when prescribing GCs
      and adapt their therapies to these risks. Two thirds of all patients under GCs
      were receiving therapy for the prevention or treatment of osteoporosis at
      documentation, high risk groups such as women over 50 even more frequently. The
      data emphasize the high importance of GCs in modern rheumatology.

PMID- 15868332
TI  - [Glucocorticoids: importance in the treatment of vasculitis].
AB  - Only the modification of natural steroids in the middle of the last century gave
      insights into the structural requirements for the biological activity of the
      glucocorticoids (GC). While the delta-4,3-keto-11-beta, 17-alpha,21-trihydroxyl
      configuration is needed for the GC-activity, an artificial additional double
      binding in position 1 and 2 lead to a four fold increase of the GC-activity. Of
      the artificial GC, prednisolone is the most frequently used compound and
      essential in the therapy of vasculitis today. Dosage, duration and way of
      application depend on the diagnosis, disease stage, -extend as well as -activity.
      Considering the use and side-effects of the GC, experiences from cohort-studies
      of the late 80-ties help at clinical decision making. For giant cell arteritis
      (GCA) it was shown, that doses of less then 60 mg/day are needed for the
      induction of remission. Concerning the visual loss in GCA, time of initiating GC
      therapy seems more important than the dosage. In the treatment of ANCA-associated
      vasculitis therapy with GC, later in combination with cyclophosphamide, lead to a
      significant reduction of mortality. Due to the fact of an increasing survival
      rate, therapy-related morbidity becomes a more and more important issue. There is
      a proven correlation between the dosage respectively duration of the GC-therapy
      and the risk of GC-associated side-effects, especially the incidence of severe
      infections. This article gives a short review of the present data of the role of
      GC in the treatment of vasculitis.

PMID- 15868333
TI  - [Glucocorticoid therapy in collagen diseases diseases].
AB  - Glucocorticoids are irreplaceable for the treatment of connective tissue diseases
      due to their strong and rapid anti-inflammatory and immuno-modulatory effects.
      Its use and their dosage depend on the activity of the disease and organ
      manifestations. There is no alternative to high doses, often even as intravenous
      pulse therapy, in life-threatening situations with imminent organ failure.
      Despite an additional immuno- suppressive medication, glucocorticosteroids are
      mandatory for long-term treatment in most cases. In special situations like high
      age, gravity or comorbidities like renal failure or hepatosis,
      glucocorticosteroids are the option with the least possible potential for
      complications. In the future, new corticosteroids and steroid sparing immuno
      suppressants like biologics will be able to reduce the spectrum and the severity
      of corticoid-induced side effects. Modern state-of-the-art therapeutic regimens
      for patients with connective tissue diseases should not only be able to
      sufficiently control the disease activity but also include the prophylaxis of
      associated comorbidities like arteriosclerosis, osteoporosis or infections.

PMID- 15868334
TI  - [Current insights into the development of new glucocorticoid receptor ligands].
AB  - Recent insights into the mechanisms of genomic and non-genomic glucocorticoid
      actions have stimulated the search for novel glucocorticoid receptor ligands.
      These efforts are driven by the need to improve the benefit-risk ratio of these
      important drugs. Glucocorticoids are very frequently and successfully used drugs
      which mediate important immunosuppressive and anti-inflammatory effects, but
      unfortunately they have pleiotropic effects causing a number of adverse reactions
      which limit their clinical use, especially at higher dosages and for longer
      periods. For this reason, novel glucocorticoid receptor ligands are being
      developed, among them selective glucocorticoid receptor agonists (SEGRAs). SEGRAs
      are drugs that predominantly induce transrepression effects (inhibition of
      protein synthesis), whereas the transactivation activity (induction of protein
      synthesis) is significantly reduced as compared with conventional glucocorticoid
      drugs. This makes sense since it became evident over the last few years that many
      adverse effects are predominantly caused by the transactivation mechanism,
      whereas anti-inflammatory effects are mostly mediated by transrepression
      mechanisms. Other interesting examples for exciting new developments are NO
      glucocorticoids and long-circulating liposomal glucocorticoids. It is, however,
      true of all these developments that further in vivo and in vitro investigations
      and clinical trials will have to define in more detail their safety-efficacy
      profile in order to answer the questions whether these drugs as "improved
      glucocorticoids" will enter clinical medicine in the near future.

PMID- 15868335
TI  - [Quality of life and psychosocial adaptation in children and adolescents with
      juvenile idiopathic arthritis and reactive arthritis].
AB  - OBJECTIVE: We sought to measure self-reported health related quality of life
      (HRQOL) and psychosocial adaptation in children and adolescents with juvenile
      idiopathic arthritis (JIA) and reactive arthritis and to determine factors
      associated with these outcomes. METHODS: We interviewed 72 children and
      adolescents with chronic arthritis, age 8-16, about HRQOL (KINDL-R-Questionnaire)
      and functional ability in activities of daily living (Childhood Health Assessment
      Questionnaire-CHAQ). Mothers reported behavior problems (Child Behavior Checklist
      CBCL). RESULTS: Children and adolescents with juvenile idiopathic arthritis and
      reactive arthritis reported lower HRQOL compared to normative data in several
      areas. Children reported lower QOL in the dimensions self-esteem; adolescents
      reported lower QOL in the dimensions physical well being and total QOL. Almost
      20% of the sample appeared to have serious behavior problems, mostly social
      isolation and depression/anxiety. Functional limitations affected HRQOL and
      behavior problems. Inpatient children and adolescents and those with shorter
      disease duration reported lower QOL than outpatient children and adolescents and
      those with longer disease duration. Best predictors for impaired HRQOL were
      functional limitations, social isolation and depression/anxiety. CONCLUSIONS:
      Self-reported HRQOL and behavior problems may be relevant outcome measures in
      children and adolescents with chronic arthritis and useful to monitor
      psychosocial support in this population.

PMID- 15868336
TI  - [Translation and psychometric testing of the Rotator Cuff Quality-of-Life Measure
      (RC-QOL) for use in German-speaking regions].
AB  - The evaluation of quality of life is an established criterion for evaluation of
      therapeutic measures. Starting from the English-speaking area a great number of
      different patient-based outcomes measures were developed to specifically question
      disorders of the musculoskeletal system and the results of treatment. Because of
      the lack of a German measurement tool for patients with rotator cuff disease the
      translation and the psychometric testing following international guidelines of
      the 34-item, multidimensional, English Rotator Cuff Quality-of-Life Measure (RC
      QOL) was undertaken. Reliability (test-retest reliability, internal consistency),
      validity, practicability and acceptance of the German version of the RC-QOL were
      tested by 102 patients with an impingement syndrome after translation and cross
      culture adaptation of the English original questionnaire. In addition, the SF-36,
      the Constant and UCLA scores were evaluated. Between the evaluations there was no
      significant difference; the Pearson correlation coefficient was 0.89 for the test
      retest reliability. The internal consistency showed a high homogeneity with a
      Cronbach Alpha-coefficient of 0.98. A Pearson correlation coefficient between
      0.67-0.76 registered a high correlation with the physical subscales of the SF-36,
      the Constant and the UCLA scores. The mean time required for completing the RC
      QOL was 12 minutes; mean time required for evaluation was 10 minutes. The
      questionnaire was incompletely answered by 16 patients (15.6%). A total of 120
      items (3.5%) were left unanswered. After successful translation and psychometric
      testing of the German version of the Rotator Cuff Quality-of-Life Measure (RC
      QOL) a multidimensional measurement tool for evaluating the quality of life of
      German-speaking patients with pathology of the rotator cuff is available.

PMID- 15868337
TI  - [A new training program--a status report: vasculitis].
AB  - Referring to the literature, it is known that structured standardized patient
      education represents an effective additional treatment in patients with chronic
      diseases. Programs are based on cognitive behavioral interventions. Within the
      last years an interdisciplinary approach for providing information on disease,
      therapies, side effects, coping strategies, nutrition and physiotherapy has been
      developed for patients with primary systemic vasculitides (PSV) in the vasculitis
      center Medical University of Luebeck/Bad Bramstedt. The contents of the seminars
      were revised and condensed into five modules. To evaluate the new program a
      documentation system consisting of patient and physician-administered
      questionnaires assessing socioeconomic, knowledge and disease-related outcome
      parameters has been designed. Patients completed the questionnaires at baseline,
      4 weeks, 6 and 12 months after training. First results show statistically
      significant improvement of knowledge and health-related quality of life.

PMID- 15868339
TI  - [Prof. Dr. Leo B. A. van de Putte].

PMID- 15868345
TI  - [Living and life with dementia].

PMID- 15868346
TI  - [A comparison of special and traditional inpatient care of people with dementia].
AB  - Recent studies reveal that approximately two thirds of the residents in German
      nursing homes suffer from some type of moderate to severe dementia. In addition
      to cognitive impairments, other psychiatric symptoms and behavior problems
      frequently impact the quality of life of the affected residents, their fellow
      residents and the nursing staff. Novel concepts of nursing care for dementia
      patients with behavior problems have been developed against this backdrop, e. g.
      within the framework of the program of special care for dementia patients in
      Hamburg. A comprehensive course study (follow-up period: approximately six
      months) of a sample population of nursing home residents and consecutive
      admissions focused upon:the degree to which the quality of life and care for
      dementia patients in Hamburg differs according to the type of care given, i. e.
      segregative (domus philosophy), or partially segregative (integration
      philosophy), and the differences between the special care of dementia patients as
      provided in Hamburg, as opposed to the traditionally integrative care of dementia
      patients as practiced in the city of Mannheim. In order to gain the most complete
      picture possible-also for persons with severe cognitive impairments-information
      was collected primarily on the basis of the assessments made by qualified nursing
      staff. In the city of Hamburg there were advantages and disadvantages,
      respectively, between segregative care (domus philosophy) and partially
      segregative care (integration philosophy): the activity rates were higher for
      care in integrative than in domus environments, and could be maintained better
      over time. Moreover, the number of visits from relatives and their involvement in
      the nursing and social care was also higher for the integrative, as opposed to
      the domus setting. Among the residents of domus-care homes, however,
      significantly more biographical information was collected, and the proportion of
      dementia patients receiving gerontopsychiatric care also was higher. Dementia
      patients in these homes also received more psychotropic medication, with
      antidementia drugs and antidepressants being prescribed significantly more
      frequently and antipsychotic drugs less frequently.The comparison of the special
      dementia care available in Hamburg with the traditional, integrative care
      available to dementia patients in Mannheim revealed a number of visible
      indicators for the quality of life that point in favor of the model program in
      Hamburg. This is apparent in the more frequent expression of positive feelings,
      the greater number of activities fostering competency, the significant
      involvement of relatives and volunteers, the greater number of social contacts
      with the staff, fewer use of physical restraint, and better gerontopsychiatric
      care. Contradictory to our expectation, however, dementia patients cared for in
      the traditional setting exhibited fewer behavior problems over time than did
      their counterparts cared for within the framework of the Hamburg model.

PMID- 15868347
TI  - [Study on the influence of group living environment on demented ill people in
      inpatient facilities].
AB  - Residential groups of twelve or fifteen persons with various levels of dementia
      have been established in three nursing homes in Nordrhein-Westfalen. A group
      comparing analysis was made three times every six months to research social
      behavior, frame of mind, progress of dementia and of physical independence. As a
      result, a considerable influence of the environmental residential groups was
      demonstrated upon social behavior and frame of mind of the habitants. On the
      other hand, the progressive course of dementia as well as the decrease of
      physical independence could not be stopped. However, within the residential
      groups all cognical and physical loss was more moderated compared to other
      studies.

PMID- 15868348
TI  - [Caregiver's burden of caring for patients with dementia in group living compared
      to to domestic and inpatient care].
AB  - The care of demented people by family caregivers is tied with severe burdens.
      Changing the providing from home care to nursing home residents or outpatient
      group living will not entirely reduce these burdens. The study is based on
      evaluated burdens of 314 nursing persons whose demented relations are cared at
      home, supported by outpatient care or day care, at geriatric care centers and at
      outpatient group living. All physically improved troubles of these three kinds of
      care do not differ considerably, compared to the self-judgements in the list of
      complaints of Giessener-Beschwerdebogen (The Giessen Subjective Complaints List)
      as well as further burden lists. Respecting further parameters in concern of
      psychic adjustment and improved burdens, the factors of serious burdens by home
      caregivers exceed considerably the nursing home residents and outpatient group
      living. However, in both providing forms, familiar caregivers come up to the
      level of burden of home care in some factors. Thus, some problems will continue
      to persist with respect to the burden symptoms when changing from home care to
      nursing home care or to a quasi inpatient care.

PMID- 15868350
TI  - [Conceptual and legal variations between the treatment of people with dementia
      receiving inpatient and ambulatory care].
AB  - In Germany, there clearly appears to be a gap between care carried out at home
      and in in-patient settings (residential nursing care). Numerous innovative
      projects of alternatively structured care, like for instance shared flats or
      group care units for people with dementia are placed in between the traditional,
      either home-based or institutionalised care patterns. It seems imperatively
      necessary to overcome the rigid separation between the inpatient sector and care
      carried out at home. In this article, backgrounds, necessities and perspectives
      of projects placed in between the traditional structures are discussed.

PMID- 15868349
TI  - [The Heidelberg instrument for the assessment of quality of life in dementia (H.
      I. L. DE.)--dimensions of quality of life and methods of organization].
AB  - The contribution is intended to describe the theoretical background and
      measurement approach of H.I.L.DE., a research project aimed to develop and
      validate a comprehensive assessment of quality of life in nursing home residents
      suffering from dementia. Proceeding from the assumption that emotions are felt
      even in advanced stages of dementia and can be interpreted on the basis of
      peoples' mimic expressions, three samples of participants were recruited from 11
      nursing homes of varying maintenance: 121 nursing home residents suffering from
      dementia, 97 professional caregivers and 101 relatives participated in the first
      wave of this study. Operational definition of quality of life in H.I.L.DE.
      proceeds from the differentiation of eight dimensions of quality of life:
      physical environment, social environment, quality of care, behavioral competence,
      medical and functional status, cognitive status, psychopathology and behavior
      disturbances, and subjective experiences of physical and social environment and
      emotional well-being. Measures of the eight dimensions involve data from medical
      examination, interviews with residents, professional caregivers and relatives,
      ecopsychological assessment of physical environment and analysis of care
      documents. First results from the H.I.L.DE.-study are used as an illustration of
      the potentials of such a comprehensive approach to the measurement of quality of
      life.

PMID- 15868351
TI  - [Development and perspectives of gerontological research: the sample case of
      housing research].
AB  - The present work addresses the historical development of environmental
      gerontology and housing research. Emphasis is placed on the development of
      ecological perspectives in gerontology as a research program, its scientific
      reception and acknowledgment in gerontology, the unfolding of housing-related
      theories and housing studies. Furthermore, the situation in Germany is juxtaposed
      against the situation in the US. As is found, between the 1930s and 1960 housing
      research gained substantial importance predominantly in the US as a consequence
      of the emergence of the field of social gerontology. There was however not much
      theoretical impetus from housing research on social and behavioral gerontology at
      large. In the time period between the 1960s and the mid 1980s many large-scale
      studies focused on housing in old age. At the same time, grand theories related
      to housing were introduced with the Ecological Theory of Aging (Lawton) as its
      flagship conception, able to have an impact on gerontology and its research
      guiding fundamental ideas (person-environment view of aging). Germany's social
      and behavioral gerontology saw during this time period the profound discussion
      of, as was frequently said, social-ecological approaches, while empirical studies
      tended to concentrate on institutions for the aged. Since the beginning of the
      1990s dementia-related themes have largely been taken over as a driving force of
      North American housing research. In some contrast, gerontological housing
      research in Germany has strongly addressed the diversity of aging in the private
      household situation. In conclusion, housing research was important for
      gerontology in terms of the promotion of a person-environment perspective of
      aging on the conceptual and empirical level. This function should continue into
      the future.

PMID- 15868352
TI  - [Development of a walking stage test (PWT) for the elderly].
AB  - The aim of the project promoted by the federal state of North-Rhine/Westphalia
      was the development of a field stage test focusing on endurance exercises of
      elderly people which withstand test-theoretical quality criteria, in particular
      that of economy. The main objectives were therefore the measurement of individual
      potential by measuring the heart rate, with simultaneous minimization of health
      risks and a close link to normal, everyday exercises. The test procedure was
      supposed to estimate the aerobic endurance of elderly people in order to enable
      us to give individual training recommendations on walking. In a three-phase
      procedure (laboratory and field ergometry, test development, and evaluation) with
      a total of 90 test persons, the individual heart rates and lactate levels were
      measured in 269 single tests. The findings show that an evaluation of the
      individual performance capability on the basis of heart rate is possible using a
      three-stage power walking test (PWT), without requiring maximum strain of the
      subjects. The PWT can therefore be seen as a diagnostic instrument available for
      the age group of the 60-80 year-olds, supplying a default for an individual
      strain dosage for walking. The test is accomplished independently of the
      respective age of the subjects and the result is an individual training plan for
      walking on the basis of an estimate of personal endurance. Developed as a staged
      test, the three levels requiring a 400 m walk on each level at different speeds,
      all the test requires is the measurement of the heart rate at the end of each
      level. The validity of the common guides for the planning of training by heart
      rate for systematic endurance training (walking) is thereby improved enabling a
      more individual training recommendation.

PMID- 15868356
TI  - Coronary aneurysms.

PMID- 15868357
TI  - [Non-atherosclerotic aneurysm of the left main coronary artery].

PMID- 15868358
TI  - Digitalis in heart failure! Still applicable?
AB  - In patients with heart failure and atrial fibrillation cardiac glycosides,
      generally in combination with beta-blockers, are indicated to control ventricular
      rate. In systolic heart failure and sinus rhythm, however, the use of digitalis
      continues to be debated. There are special concerns that cardiac glycosides might
      lead to an increased mortality rate in women. Retrospective analyses, however, do
      not indicate any sex-based differences in the effectiveness of cardiac
      glycosides. Beneficial effects of cardiac glycosides in heart failure seem to be
      related to the attenuation of sympathetic activation and neurohumoral
      alterations, which is already obtained at low digoxin serum concentrations, while
      high serum levels are associated with increased mortality. Therefore, in patients
      with sinus rhythm who remain symptomatic under an optimized therapy with ACE
      inhibitors, beta-blockers and diuretics in addition to digitalis should be
      considered regardless of the gender. However, target serum digoxin concentrations
      should be low in a range of 0.5 to 0.8 ng/ml.

PMID- 15868359
TI  - [Cardiac manifestations of muscular dystrophies].
AB  - Muscular dystrophies (MD) are a clinically and genetically heterogeneous disease
      group. In the last few years, remarkable progress has been made in understanding
      the close und various relations between skeletal muscle disease and heart muscle
      disease. Cardiac involvement has been documented in a number of primary MDs and
      is even the dominant feature in some of them. The myocardium can be affected in
      the form of a dilated cardiomyopathy while the conduction system can be affected
      resulting in arrhythmias and conduction defects. Many patients with MD die
      because of cardiac complications like sudden cardiac death or congestive heart
      failure. Detailed clinical data about cardiac involvement are available for
      Duchenne/Becker MD, Emery-Dreifuss MD, myotonic dystrophy, and the different limb
      girdle MDs. Cardiac manifestations were also found in congenital MD, central core
      disease, proximal myotonic myopathy, and nemaline myopathy. No data about cardiac
      abnormalities are available in oculopharyngeal MD and rippling muscle disease.
      The heart of patients with primary MD should be carefully investigated because of
      the life-threatening events caused by cardiac complications. There is a strong
      need for a close collaboration between neurologists and cardiologists in order to
      provide optimal disease management for the affected patients.

PMID- 15868360
TI  - The validation of fractional flow reserve in patients with coronary multivessel
      disease: a comparison with SPECT and contrast-enhanced dobutamine stress
      echocardiography.
AB  - Fractional flow reserve (FFR) is a new but well established parameter for the
      hemodynamic evaluation of coronary stenoses. A FFR below 0.75 was validated as
      functionally significant in coronary one or two vessel disease. This study was
      designed to prospectively define the best FFR cut off value (BCV) in patients
      with multivessel disease using two noninvasive tests, myocardial perfusion
      scintigraphy (SPECT) and contrast-enhanced dobutamine stress echocardiography
      (DSE) as reference methods. METHODS: 47 symptomatic patients (29 male, mean age
      64+/-10 yrs) with angiographically intermediate coronary lesions (50-75% diameter
      stenosis) entered the study. DSE (5-40 microg/min/kg dobutamine) was performed
      after intravenous injection of a second generation transpulmonary contrast agent.
      SPECT (Tc-99m-MIBI) was done at peak stress. All tests (DSE, SPECT and FFR) were
      performed within 4 weeks. RESULTS: SPECT yielded positive results in 15 and DSE
      in 16 patients, respectively. Mean FFR measured in the target lesion (RCA n=10;
      LAD n=22, RCX n=15) was 0.80+/-0.13. FFR was <0.75 in 15 patients. By performing
      a ROC analysis the BCV (highest sum of sensitivity and specificity) was found at
      0.75. At this cut off value using both non-invasive tests as reference method,
      sensitivity and specificity were 83 and 77%. CONCLUSION: In patients with
      multivessel disease, a FFR <0.75 identifies a hemodynamically relevant lesion as
      compared to DSE and SPECT. This study underlines that FFR criteria are also
      applicable in patients with complex coronary artery disease.

PMID- 15868361
TI  - Elevated serum markers for collagen synthesis in patients with hypertrophic
      cardiomyopathy and diastolic dysfunction.
AB  - OBJECTIVES: The hypothesis of impaired collagenolysis in patients with
      hypertrophic cardiomyopathy (HCM) was tested by measuring serum markers of type-I
      collagen metabolism. These markers were correlated with echocardiographic
      parameters of diastolic function. BACKGROUND: HCM is a common disease in the
      adult population with a wide range of clinical manifestations. Left ventricular
      hypertrophy and increased intramyocardial collagen content are known to cause
      diastolic dysfunction in patients with HCM. METHODS: In 26 patients with HCM and
      38 control subjects (aged: 57+/-3 and 54+/-2 years, p=n.s.) serum levels of
      collagenolytic matrixmetalloproteinase-1 (MMP-1) and its inhibitor TIMP-1, the
      markers for collagen type-I synthesis (PICP) and degradation (ICTP) were
      determined by ELISA and RIA. Diastolic function were determined by Doppler
      echocardiography. RESULTS: Free TIMP-1 was elevated in HCM compared to controls
      (216,78+/-9,89 vs 183.77+/-7.57 ng/ml ; p=0.006) as well as PICP (165.92+/-10.26
      vs 114.57+/-6.38 mug/l; p<0.001). Free MMP-1 was significantly lower in HCM
      (1.13+/-0.20 vs 2.33+/-0.34; p=0.01). ICTP did not differ. The MMP-1/TIMP-1 ratio
      was significantly lower in HCM (0.006+/-0.001 vs 0.012+/-0.001, p=0.003). PICP
      correlated positively with diastolic E/A ratio (r=0.389; p=0.05) and septal
      thickness (r=0.484; p=0.01). CONCLUSIONS: Serum marker of collagen synthesis
      (PICP) is increased in patients with HCM. Increased marker for inhibition of
      collagenolysis (TIMP-1) and a disturbed balance of collagen synthesis and
      degradation (ratio) with a predominance of inhibition of collagenolysis indicates
      collagen accumulation (fibrosis), which explains passive diastolic dysfunction in
      patients with HCM.

PMID- 15868363
TI  - Radiofrequency catheter ablation of two accessory pathways with different
      unidirectional conduction properties.
AB  - Simultaneous occurrence of narrow and broad QRS complex tachycardias in patients
      with WPW syndrome usually indicates a macroreentry in an orthodromic
      atrioventricular reentry-tachycardia using the AV node as antegrade and the
      accessory pathway as retrograde conduction and vice versa in an antidromic
      circuit. We report on a 32-year-old woman with WPW syndrome presenting with both
      a narrow and a broad QRS complex tachycardia using two accessory pathways with
      different unidirectional conduction properties in combination of an exclusively
      antegrade conducting AV node. This case report describes conventional mapping
      techniques and ablation of this unusual entity of a WPW syndrome.

PMID- 15868362
TI  - Influence of the angiotensin converting enzyme inhibitor ramipril on high
      sensitivity C-reactive protein (hs-CRP) in patients with documented
      atherosclerosis.
AB  - Some medications have been shown to produce reductions in hs-CRP levels after
      initiating therapy. Whereas the role of the renin-angiotensin system in the
      inflammatory process has been documented in more detail during the last few
      years, the impact of an ACE-inhibitor therapy on this process has not been fully
      understood so far. The aim of this study was to investigate the effect of a
      therapy with the angiotensin-converting enzyme (ACE) inhibitor ramipril on hs-CRP
      plasma concentrations in patients with atherosclerosis. METHODS AND RESULTS: A
      total of 24 patients were enrolled in this prospective, uncontrolled, open-label
      multicenter study. Inclusion criteria were documented atherosclerosis, baseline
      high-sensitivity C-reactive protein between 3 and 12 mg/l, LDL-Cholesterol < or
      =150 mg/dl and no previous treatment with ACE inhibitors or angiotensin receptor
      blockers. Ten patients, pretreated with statins, and 10 patients not previously
      treated with statins were eligible for statistical analysis. Baseline high
      sensitivity C-reactive protein was significantly decreased from 3.99+/-1.61 mg/l
      (mean+/-SD) to 2.72+/-1.19 mg/l (-32%) after 3 months treatment with 10 mg
      ramipril daily (p=0.0002). The decrease was more pronounced in patients who had
      not been treated with statins previously (-1.50 mg/l+/-1.44 mg/l) compared to
      those who were pretreated (-0.90 mg/l+/-0.93 mg/l). CONCLUSIONS: The ACE
      inhibitor ramipril administered in a daily dose of 10 mg to patients with
      atherosclerosis reduces the high-sensitivity C-reactive protein concentration.
      This effect may contribute to cardiovascular risk reduction mediated by ramipril
      aside from the blood pressure lowering effect.

PMID- 15868364
TI  - [Facioscapulohumeral muscle dystrophy and heart disease].
AB  - Cardiac involvement is well known in a number of skeletomuscular diseases but not
      in facio-scapulohumeral muscular dystrophy (FSHD). We report on a 71 year old
      woman with progressive cardiac insufficiency in FSHD, which was also confirmed by
      molecular analysis in one of the two daughters affected by the disease. Autopsy
      of the deceased patient showed the typical changes in skeletal muscles including
      focal inflammatory infiltrates in the diaphragm and, in addition, cardiac
      muscular involvement. The histological changes resembled those seen in primary
      cardiomyopathy despite the normal muscle mass volume. Both clinically and
      morphologically, the cardiac disease was the cause of death in this patient with
      FSHD.

PMID- 15868365
TI  - Combined open heart surgery and replacement of the brachiocephalic trunk. A safe
      method for simultaneous central revascularization.
AB  - OBJECTIVE: We investigated the feasibility of open heart surgery with combined
      central vascular surgery and present the results from 9 years of experience.
      PATIENTS AND METHODS: Of a total of nine patients, eight received coronary artery
      bypass grafting and one patient aortic valve replacement. Concerning vascular
      surgery a replacement of the brachiocephalic trunk using a Dacron prosthesis as
      an end-to-end anastomosis or as a bifurcations prosthesis was performed. Two
      patients underwent additional ipsilateral desobliteration of the internal carotid
      artery. RESULTS: The hospital stay was between 8 and 30 days (median 15). The
      duration of the whole operation was median 318 min (range: 294-345 min),
      perfusion time 67 min (range: 62-146 min), myocardial ischemic time 27 min
      (range: 11-83 min). There was no case of in-hospital death. Follow-up was
      available up to 7.5 years in 7 patients. Five patients show a satisfactory
      cardiac status. A sign for ischemic cerebral events or embolization was not
      observed. CONCLUSION: Due to the low complication rate, we conclude that
      concomitant open heart surgery with replacement of the brachiocephalic trunk can
      be performed with low risk; it allows-in contrast to direct endarterectomy
      complete central revascularization and hence should be preferred compared to
      surgical therapy in separate settings.

PMID- 15868366
TI  - [Cardiovascular medicine in the German diagnosis-related group--(G-DRG) system
      2005].
AB  - The German diagnosis-related Group (G-DRG) System has recently been published in
      its third version. From 2005 on, this system will be the definite measure for the
      budgets of nearly all german hospitals. The preliminary phase with no budget
      reduction or redistribution being made and in which an inappropriate
      classification system had no negative impact on reimbursement has, thus, come to
      an end. At present, many hospitals are struggling in an economic competition
      about the independence or maintenance of the hospital or several sub-departments.
      The changes in the classification system with regard to a marked increase in the
      number of G DRGs, a modified grouping-logic, more properly determined reductions
      and extra charges for low and high outlier as well as the introduction of further
      additional charges contribute thereby to a better covering of services and
      treatments of cardiovascular patients. However, while many of the known problems
      have been eliminated, there are still weaknesses in the G-DRG System even
      concerning cardiovascular medicine. The G-DRG System has to be adapted
      continuously with consultation of the clinical expertise of the respective
      medical societies. The most important new aspects and changes in the G-DRG System
      2005 and the accompanied execution regulations are explained with special view on
      cardiology.

PMID- 15868369
TI  - Metabolic aspects of hepatitis C viral infection: steatohepatitis resembling but
      distinct from NASH.
AB  - Although the target of hepatitis C virus (HCV) infection is the liver, it has
      become progressively more evident that HCV can induce diseases in numerous
      organs. Recently, much attention has been drawn to metabolic disorders in HCV
      infection. Initially, hepatic steatosis and disturbances in lipid metabolism were
      found to be characteristic of HCV infection, and, subsequently, a correlation was
      noted between HCV infection and diabetes. It is now evident that HCV, by itself,
      can induce insulin resistance by way of disturbing the intracellular signaling
      pathway of insulin by the function of HCV core protein. Insulin resistance,
      caused by HCV infection, evolves to type 2 diabetes when superimposed on a high
      fat diet and obesity. The fact that HCV infection induces insulin resistance by
      the virus itself may influence the progression of chronic hepatitis and open up
      novel therapeutic approaches. When hepatitis C is compared with nonalcoholic
      steatohepatitis (NASH), there are a number of similarities and several
      differences. From the metabolic aspect, hepatitis C resembles NASH in numerous
      features, such as the presence of steatosis, serum dyslipidemia, and oxidative
      stress in the liver, suggesting that hepatitis C is a steatohepatitis. In
      contrast, there are noticeable differences between hepatitis C and NASH, in that
      HCV modulates cellular gene expression and intracellular signal transduction,
      including the activation of mitogen-activated protein (MAP) kinase and
      transcription factor activator protein (AP)-1, while such details have not been
      noted for NASH. This difference may explain the markedly higher incidence of HCC
      development in chronic hepatitis C compared with that in NASH. HCV infection
      needs to be viewed not only as a liver disease but also as a metabolic disease,
      and this viewpoint could open up a novel way to the molecular understanding of
      the pathogenesis of hepatitis C, as a virus-associated steatohepatitis (VASH).

PMID- 15868370
TI  - SNPs in the promoter region of the osteopontin gene as a marker predicting the
      efficacy of interferon-based therapies in patients with chronic hepatitis C.
AB  - BACKGROUND: The T-helper (Th)1 immune reaction is essential for the eradication
      of hepatitis C virus (HCV) during interferon (IFN) therapy in patients with
      chronic hepatitis C. Osteopontin is a cytokine crucial for the initiation of the
      Th1 response. Recently, we identified four single-nucleotide polymorphisms (SNPs)
      in the promoter region of the osteopontin gene (OPN), at nucleotide (nt) -155, 
      443, -616, and -1748, and suggested that the SNP at nt -443 was a marker
      reflecting hepatitis activity in patients with HCV. Therefore, we examined the
      possibility that SNPs in OPN were also markers predicting the therapeutic
      efficacy of IFN in patients with chronic hepatitis C. METHODS: Blood was
      collected from 77 patients with chronic hepatitis C who had received either IFN
      monotherapy or IFN-ribavirin combination therapy (IFN-based therapies). SNPs in
      OPN, MxA, MBL, and LMP7 were analyzed by Invader assay. RESULTS: Promoter SNPs of
      OPN at nt -155, -616, and -1748 showed linkage disequilibrium at 100% to each
      other. Sustained virological response (SVR) was observed in 58% of all patients.
      The SVR rate was higher in patients with the G/G or G/A alleles in the OPN
      promoter SNP at nt -1748 than in those with A/A (85% vs 45%; P < 0.05). The SVR
      rate was also higher in patients with T/T at nt -443 than in those with C/C or
      C/T (86% vs 47%; P < 0.05). Such differences were particularly evident in
      patients with HCV genotype 1b who had a pretreatment viral load greater than 100
      KIU/ml. All the patients who had G/G or G/A at nt -1748 and T/T at nt -443
      obtained an SVR. On the other hand, there was no relationship between the
      efficacy of IFN-based therapies and SNPs in MxA, MBL, and LMP7, which had been
      shown to have association with the response to IFN monotherapies. CONCLUSIONS:
      SNPs in the promoter region of OPN may be useful as a marker to predict the
      efficacy of IFN-based therapies in patients with chronic hepatitis C, and further
      investigation regarding their real significance is warranted in a large series of
      patients.

PMID- 15868371
TI  - Clinical study of choledochocele: is it a risk factor for biliary malignancies?
AB  - BACKGROUND: We aimed to clarify the clinical characteristics of choledochocele
      and to evaluate the possibility of choledochocele as a risk factor for biliary
      malignancies. METHODS: The clinical feature, the configuration of the
      pancreatobiliary ductal system, coexistent pancreatobiliary lesions, and amylase
      level in bile in 21 patients with choledochocele were reviewed. The correlation
      between the configuration, comorbid diseases, and amylase level in the bile was
      investigated. RESULTS: There was a female predominance, and 57% of the patients
      showed abdominal pain. Quite a few patients showed elevation of the levels of
      hepatobiliary enzymes. The configuration of the pancreatobiliary ductal system
      and choledochocele was classified into two categories: type I, where the
      choledochocele and pancreatic duct were visualized independently or
      simultaneously (90.5%); and type II, where the pancreatic duct was visualized
      after filling of the choledochocele (9.5%). Among coexistent bilio-pancreatic
      diseases, biliary stone diseases were the most frequent. Biliary malignancy was
      seen in 3 patients (14.3%). The amylase level in the bile was high in 50% (4/8)
      of the patients examined. The rate of abnormal elevation of amylase level in the
      bile in the two types of pancreatobiliary ductal system and choledochocele was
      3/7 and 1/1, respectively. CONCLUSIONS: The prevalence of organic abnormal
      arrangement of the pancreatobiliary ductal system in which the choledochocele
      serves as a common channel is low. However, there are patients with suspected
      functional abnormal arrangement of the pancreatobiliary ductal system, who may
      possibly be a high-risk group for biliary malignancy.

PMID- 15868372
TI  - Osteopontin expression in ulcerative colitis is distinctly different from that in
      Crohn's disease and diverticulitis.
AB  - BACKGROUND: The aim of the present work was to assess osteopontin (OPN)
      expression in the colon tissues of ulcerative colitis (UC), Crohn's disease (CD),
      and diverticulitis (Div) patients. METHODS: This study included three groups: the
      UC group, CD group, and Div group. Immunohistochemical staining was performed,
      using an immunoperoxidase method. RESULTS: Regarding OPN expression in intestinal
      epithelial cells, no difference was noted among the three groups. However, in the
      submucosa of the UC group, the ratio of two types of large cells (oval and
      spindle-shaped) expressing OPN was 61.2 +/- 14.4% (mean +/- SD), which was
      significantly higher than that in the CD group (14.9 +/- 7.0%; P < 0.05) and that
      in the Div group (11.2 +/- 6.1%; P < 0.05). In addition, in the UC group, the
      ratio of these cells in the subserosa (50.1 +/- 15.0%; mean +/- SD) was
      significantly higher than that in the CD group (16.9 +/- 6.2%; P < 0.05) and that
      in the Div group (12.6 +/- 5.7%; P < 0.05). In a serial section study, the oval
      shaped cells were stained for anti-CD 68, while the spindle-shaped cells were
      stained for anti-vimentin. CONCLUSIONS: OPN in two types of large colon
      infiltrating cells is possibly related to one of the pathogenic factors of UC.

PMID- 15868373
TI  - Does Helicobacter pylori attack ghrelin-producing cells?

PMID- 15868374
TI  - Where is the primary site of action of CCK for initiating sphincter of Oddi
      relaxation?

PMID- 15868375
TI  - A mutated p53 status did not prevent the induction of apoptosis by sulforaphane,
      a promising anti-cancer drug.
AB  - We investigated apoptosis induction by sulforaphane on three cell lines
      characterized by a different p53 status. In particular, we used p53-knock-out
      fibroblasts from newborn mice transfected with the p53-Ser220 mutation, observed
      in Li-Fraumeni Syndrome patients, as a model of mutated p53 status. Moreover,
      immortalized fibroblasts from newborn mice expressing or lacking p53 (p53 +/+ and
      p53-/-, respectively) have been used to verify whether mutated p53 status could
      prevent sulforaphane-induced apoptotic events. Sulforaphane was able to induce
      apoptosis on all three cell lines. Indeed, the caspase-3 assays and poly(ADP
      ribose)polymerase (PARP) cleavage data indicated that sulforaphane stimulated
      caspase-3-like activity and degradation of PARP. However, cells with a wild-type
      or mutated p53 appeared to be more sensitive to the effects of sulforaphane than
      cells lacking p53. Taken together, our results suggest that sulforaphane could
      act by a p53-independent pathway. For this reason, sulforaphane can be viewed as
      a novel agent useful not only in the treatment of Li-Fraumeni-associated tumors
      but also drug resistant tumors where p53 dysregulation is a feature.

PMID- 15868376
TI  - Induction of apoptosis by flavopiridol unrelated to cell cycle arrest in germ
      cell tumour derived cell lines.
AB  - BACKGROUND: Germ cell tumours (GCTs) are highly sensitive to cisplatin-based
      chemotherapy. The inability to arrest the cell cycle at the G1/S-check-point due
      to a lack of retinoblastoma gene product RB has been suggested as one potential
      explanation for this feature. Flavopiridol (FP), an inhibitor of cyclin dependent
      kinases, causes cell cycle arrest or apoptosis depending on the relation of the
      transcription factor E2F1 and RB. METHODS: The effect of FP was evaluated in GCT
      derived cell lines NT2, 2102 EP and NCCIT in comparison to cell lines derived
      from ovarian cancer (SKOV), breast cancer (MCF7), and cervical cancer (HeLa)
      using the MTT-assay. Cell cycle progression and induction of apoptosis were
      assessed by flow cytometry and immunoblot analysis of PARP-cleavage. RESULTS: FP
      did not affect cell cycle progression and proliferation of GCT cell lines at
      sublethal doses. At higher concentrations, cell death occurred independent of
      cell cycle progression. The IC50 was approximately fivefold lower for the three
      GCT cell lines (60/60/70 nM) than for the other tumour cell lines tested
      (350/280/300 nM). Lethal doses in vitro were markedly lower than plasma
      concentrations of FP achieved in clinical studies. In vitro sensitivity to FP did
      not correlate with that to cisplatin. The cell lines NTera2 and NCCIT showed
      comparable responses to FP despite differing in their IC50 to cisplatin by factor
      4. Flow cytometry and immunoblot for PARP indicated apoptotic cell death induced
      by FP. Synergism between either cisplatin or paclitaxel and FP was not observed.
      However, at low concentrations, cytotoxicity of FP and cisplatin appeared to be
      additive. CONCLUSION: These prelinical investigations suggest a significant
      antitumour activity of FP in GCT. GCT derived cell lines were far more responsive
      to FP than cell lines derived from other solid tumours. In contrast to other
      models, FP did not induce cell cycle arrest in the GCT-derived cell lines tested,
      possibly due to the known lack of RB-expression in GCTs. However, apoptosis was
      induced unrelated to cell cycle progression already at low concentrations. No
      cross resistance between FP and cisplatin was observed. A clinical trial
      evaluating the activity of FP in patients with cisplatin-refractory GCTs appears
      to be warranted.

PMID- 15868377
TI  - Cryptophycins-309, 249 and other cryptophycin analogs: preclinical efficacy
      studies with mouse and human tumors.
AB  - Cryptophycins-1 and 52 (epoxides) were discovered to have in-vitro and in-vivo
      antitumor activity in the early 1990s. The chlorohydrins of these, Cryptophycins
      8 and 55 (also discovered in the early 1990s) were markedly more active, but
      could not be formulated as stable solutions. With no method to adequately
      stabilize the chlorohydrins at the time, Cryptophycin-52 (LY 355073) entered
      clinical trials, producing only marginal antitumor activity. Since that time,
      glycinate esters of the hydroxyl group of the chlorohydrins have been synthesized
      and found to provide stability. Three of the most active were compared herein.
      Cryptophycin-309 (C-309) is a glycinate ester of the chlorohydrin Cryptophycin
      296. The glycinate derivative provided both chemical stability and improved
      aqueous solubility. After the examination of 81 different Cryptophycin analogs in
      tumor bearing animals, C-309 has emerged as superior to all others. The following
      %T/C and Log Kill (LK) values were obtained from a single course of IV treatment
      (Q2d x 5) against early staged SC transplantable tumors of mouse and human
      origin: Mam 17/Adr [a pgp (+) MDR tumor]: 0%T/C, 3.2 LK; Mam 16/C/Adr [a pgp (-)
      MDR tumor]: 0%T/C, 3.3 LK; Mam 16/C: 0%T/C, 3.8 LK; Colon 26: 0%T/C, 2.2 LK;
      Colon 51: 0%T/C, 2.4 LK; Pancreatic Ductal Adenocarcinoma 02 (Panc 02): 0%T/C,
      2.4 LK; Human Colon HCT15 [a pgp (+) MDR tumor]: 0%T/C, 3.3 LK; Human Colon
      HCT116: 0%T/C, 4.1 LK. One additional analog, Cryptophycin-249 (C-249, the
      glycinate of Cryptophycin-8), also emerged with efficacy rivaling or superior to
      C-309. However, there was sufficient material for only a single C-249 trial in
      which a 4.0 LK was obtained against the multidrug resistant breast adenocarcinoma
      Mam-16/C/Adr. C-309 and C-249 are being considered as second-generation clinical
      candidates.

PMID- 15868378
TI  - Semi-physiological model describing the hematological toxicity of the anti-cancer
      agent indisulam.
AB  - Indisulam (N-(3-chloro-7-indolyl)-1,4-benzenedisulfonamide, GOAL, E7070) is a
      novel anti-cancer drug currently in phase II clinical development for the
      treatment of solid tumors. Phase I dose-escalation studies were conducted
      comparing four treatment schedules. Neutropenia and thrombocytopenia were dose
      limiting in all schedules. The aim of this study was to describe the extent and
      the time course of the hematological toxicity and its possible schedule
      dependency using a semi-physiological model. Data from 142 patients were analyzed
      using NONMEM. The semi-physiological model comprised a progenitor blood cell
      compartment, linked to the central circulation compartment, through 3 transition
      compartments representing the maturation chain in the bone marrow. Plasma
      concentrations of the drug were assumed to reduce the proliferation rate in the
      progenitor compartment according to a linear function. A feedback mechanism was
      included in the model representing the rebound effect of endogenous growth
      factors. The model was validated using a posterior predictive check. The model
      adequately described the extent and time course of neutropenia and
      thrombocytopenia. The mean transition time (MTT, i.e. maturation time in bone
      marrow) of neutrophils was increased by 47% in patients who received indisulam as
      a weekly dose administered for four out of every six weeks. For platelets, MTT
      was increased by 33% in patients who received this schedule and also in patients
      who received a continuous 120-h infusion. The validation procedure indicated that
      the model adequately predicts the nadir value of neutrophils and platelets and
      the time to reach this nadir. A semi-physiological model was successfully applied
      to describe the time course and extent of the neutropenia and thrombocytopenia
      after indisulam administration for four treatment schedules.

PMID- 15868379
TI  - Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy.
AB  - Based on the activity of menadione (M) in the human tumor stem cell assay, we
      conducted a phase I trial of M in patients with advanced cancer. Forty patients
      (19 men, 21 women) were treated with 90 courses of M; 82 treatment courses are
      evaluable for toxicity. The median patient age, Karnofsky performance status, and
      number of prior chemotherapy regimens were 61 years (range 32-74 years), 80%
      (range 50-100%), and two, respectively. M was given by a short (1-5 h)
      intravenous infusion every 3 weeks, starting at 40 mg/m2 and escalating by
      modified Fibonacci scheme to 1360 mg/m2. Toxicity was graded according to the
      Southwest Oncology Group toxicity scale with defined hypersensitivity reaction
      (HSR) scales. No grade > or =2 hematologic toxicity was observed. Non-hematologic
      toxicity consisted of a HSR syndrome of paresthesiae of the extremities, facial
      flushing, burning of the eyes and mucous membranes, chest pain and dyspnea. HSR
      was defined as Grade I toxicity by the presence of facial numbness, flushing,
      and/or a tingling sensation or burning of the eyes and mucous membranes. Grade II
      toxicity was defined as the presence of the same above symptoms plus chest
      tightness, paresthesiae of extremities and/or dyspnea and chest pain. These
      toxicities were grade 1 in 3 of 4 patients at a dose of 840 mg/m2. At 1360 mg/m2,
      2 of 13 patients suffered grade 1 HSR and 7 of 13 grade 2 HSR. No objective
      partial or complete responses were observed. Plasma menadione concentrations
      peaked at 1.9-7.4 microM during the infusion in 3 patients receiving 1360 mg/m2.
      Further phase 1 and 2 combination trials using longer infusion durations have
      resulted from this trial.

PMID- 15868380
TI  - A phase I trial of irinotecan (CPT-11) with amifostine in patients with
      metastatic colorectal cancer.

PMID- 15868382
TI  - Multi-centre Phase II trial of the polyamine synthesis inhibitor SAM486A
      (CGP48664) in patients with metastatic melanoma.
AB  - PURPOSE: To determine the activity and tolerability of SAM496A, an inhibitor of S
      adenosylmethionine decarboxylase (SAMDC), in patients with metastatic melanoma
      who had not received prior chemotherapy. Selected patients were offered
      participation in two sub-studies examining early changes in tumor metabolism with
      FDG-PET and changes in tumor polyamine content. PATIENTS AND METHODS: Fifteen
      patients with measurable metastatic melanoma, normal cardiac function, and no
      known CNS metastases were eligible and received SAM486A by 1-hour IV infusion
      daily for 5 days every 3 weeks. Response was assessed by SWOG criteria. RESULTS:
      No patient had a confirmed partial response. Fatigue/lethargy, myalgia and
      neutropenia were the main toxicities but no febrile neutropenia or grade 4 non
      hematological toxicity occurred. Five patients had PET scans pre-treatment and on
      days 8-12 of cycle 1. No patient had reduction of tumor metabolism. Serial biopsy
      in one patient showed alterations in polyamines consistent with SAMDC inhibition.
      CONCLUSIONS: Using the present dose and schedule of administration, SAM486A does
      not have significant therapeutic potential in patients with metastatic melanoma.

PMID- 15868381
TI  - Weekly irinotecan plus UFT and leucovorin as first-line chemotherapy of patients
      with advanced colorectal cancer.
AB  - We evaluated the antitumoral efficacy and safety of CPT-11 125 mg/m2 (weekly 90
      min i.v. infusion; days 1, 8 and 15) combined with UFT (oral combination of
      tegafur and uracil) 200 mg/m2/day plus leucovorin (LV) 45 mg/m2/day (both divided
      into three separate oral doses every 8 h, days 1-21) every 4 weeks as first-line
      chemotherapy of metastatic colorectal cancer (CRC). Fifty-three patients > or =18
      years old with histologically confirmed diagnosis of advanced CRC and
      bidimensionally measurable disease were enrolled. Three patients (6%) showed CR
      and 8 patients (15%) showed PR (ORR = 21% (95% CI, 10-32). Stable disease was
      reported in 19 patients (36%) [tumor control rate = 57% (95% CI, 43-70)]. The
      median time to progression and overall survival were 7.9 and 18.2 months,
      respectively (1-year rate = 74%; 2-years rate = 26%). CPT-11/UFT/LV treatment was
      well tolerated: the most reported grade 3/4 toxicities were neutropenia (11% of
      patients) and delayed diarrhea (28% of patients). No significant differences in
      response rate, survival or toxicity were found between younger (< or =65 years)
      and older patients (> 65 years). Weekly CPT-11 plus UFT/LV was found effective
      and safe as first-line chemotherapy for metastatic CRC. The addition of CPT-11 to
      UFT/LV doubled the response rate compared to the results previously reported with
      UFT/LV, while myelosuppression remained low.

PMID- 15868383
TI  - Phase II trial of dolastatin-10 in patients with advanced breast cancer.
AB  - PURPOSE: Phase II multicenter cooperative group study investigated the efficacy
      and toxicity of the novel anti-microtubule agent dolastatin-10 in patients with
      advanced breast cancer. PATIENT AND METHODS: Twenty-one patients with measurable
      metastatic breast cancer were treated with dolastatin-10 at a dose of 400 mcg/m2
      by intravenous bolus once every 3 weeks. Patients must have received a total of 1
      or 2 prior chemotherapy regimens and have an Eastern Cooperative Oncology Group
      performance status of 0-2. Patients received this treatment as either a first (n
      = 11) or second-line (n = 10) chemotherapy for metastatic disease. Eighteen
      patients (86%) had received a prior anthracycline. The National Cancer Institute
      provided the dolastatin-10. RESULTS: One out of 21 patients (5%; 95% CI: 0-24%)
      achieved a partial remission for a duration of 113 days. Four patients maintained
      stable disease for a median of 87 days. A total of 58 courses of dolastatin-10
      were administered. Patients received a median of two cycles of dolastatin-10.
      Hematologic toxicity was moderate, with 8 patients developing grade 4
      neutropenia, and 5 with grade 3 neutropenia; one grade 3 febrile neutropenia was
      observed. These episodes of grade 3 and 4 neutropenia were experienced on 36% of
      the treatment cycles. Non-hematologic toxicity was uncommon. CONCLUSION: While
      the toxicity profile of dolastatin-10 was acceptable, it had minimal activity in
      this advanced breast cancer study. We are not pursuing further clinical trials of
      this agent in the setting of advanced breast cancer.

PMID- 15868384
TI  - Randomized phase II evaluation of aprinocarsen in combination with gemcitabine
      and cisplatin for patients with advanced/metastatic non-small cell lung cancer.
AB  - Aprinocarsen is a specific antisense oligonucleotide inhibitor of protein kinase
      C-alpha. This study aimed to evaluate the response rate to combination therapy
      with aprinocarsen, gemcitabine and cisplatin, in chemonaive patients with
      advanced/metastatic NSCLC. Secondary objectives included comparison of response
      rate, time to event efficacy parameters, and toxicities on the 2 treatment arms.
      Patients with stage IV, or stage IIIB disease (N3 and/or pleural/pericardial
      effusion), were randomized to either control or experimental arm. Patients on
      both arms received gemcitabine 1250 mg/m2 on days 1 and 8, and cisplatin 80 mg/m2
      on day 1 of a 3-week cycle. Additionally, on the experimental arm, aprinocarsen
      was administered as 2 mg/kg continuous iv infusion on days 1-14, every 21 days. A
      total of 18 enrolled patients were randomized on the 2 arms. Further enrollment
      was terminated in March 2003 as a result of a phase III trial suggesting that
      aprinocarsen did not have an added survival benefit when combined with paclitaxel
      and carboplatin therapy in patients with NSCLC. Patients received a median of 4
      cycles on control arm and 2.5 cycles on experimental arm. The response rate was
      16.7% in the experimental arm and 44.4% in the control arm. Most frequent grade
      3/4 toxicities were hematologic, with a higher incidence of thrombocytopenia in
      the experimental arm (87.5% vs. 33.3%). Despite the 14-day continuous infusion
      schedule, infection rate was not increased in the experimental arm. The present
      study did not show any advantage, in response rate or secondary endpoints, with
      aprinocarsen; however, the toxicity was not unduly increased, and aprinocarsen
      regimen was safely administered.

PMID- 15868385
TI  - A new Mother-to-Infant Bonding Scale: links with early maternal mood.
AB  - Some mothers find it hard to relate to their new baby, and such failure may have
      long-term effects on the infant. This has been a neglected area of research. A
      new simple 8 item self-rating mother-to-infant bonding questionnaire has been
      designed to assess the feelings of a mother towards her new baby. A principal
      components and reliability analysis demonstrated an alpha score of 0.71. One
      hundred and sixty two women filled in the Kennerley Blues Scale, the Edinburgh
      Postnatal Depression Scale (EPDS) the Highs Scale and the new Mother to Infant
      Bonding Scale on day 3 postpartum. Twelve weeks later they were sent the EPDS and
      the Bonding scales again. One hundred and forty four returned all questionnaires.
      There was a strong correlation between the Bonding scores at 3 days and at 12
      weeks (r(s)=0.54 p<0.001). Multiple regression analysis showed that those with
      raised Blues scores had worse, and those with raised Highs scores had better
      bonding at 3 days. Those with raised EPDS scores at 3 days (13 and over) had
      worse bonding scores in the "first few weeks" (median 4 versus 1, p = 0.028), as
      recalled at 12 weeks. This simple questionnaire is acceptable for use with
      mothers and gives significant correlations with their early mood.

PMID- 15868386
TI  - Post-abortion psychosis.

PMID- 15868387
TI  - A screening study of antidepressant treatment rates and mood symptoms in
      pregnancy.
AB  - STUDY DESIGN: As part of a large screening study of perinatal depression,
      pregnant women were screened for demographic, depression and treatment variables
      in obstetrics clinics. Women taking antidepressant medication prior to conception
      were included in the sample as the study aimed to document rates of
      antidepressant medication use, and relationship to depressive symptomatology.
      RESULTS: Among women who reported using antidepressant medications within 2 years
      prior to screening (n = 390, or 11% of all women), 22% reported current use of
      these medications. Women who reported using antidepressant medications (52%) and
      those who discontinued them (49%) evidenced elevated depressive symptoms during
      pregnancy. CONCLUSIONS: Both women who discontinue and some who continue
      antidepressants during pregnancy demonstrate depressive symptoms, suggesting sub
      optimal management of both groups. Future studies should carefully assess the
      adequacy of treatments prescribed as well as the monitoring and adherence of
      recommended treatments. Full symptom remission should be the goal for antenatal
      and postnatal depression in order to minimize risk to mother and baby.

PMID- 15868388
TI  - Nefazodone for the treatment of postpartum depression.

PMID- 15868389
TI  - Lamotrigine in pregnancy and lactation.

PMID- 15868390
TI  - Prevalence of postpartum depression in a Moroccan sample.
AB  - The aim of the present study was to determine the prevalence and factors
      associated with post-partum depression among Moroccan mothers. The authors
      interviewed 144 mothers at 2 and 6 weeks, and at 6 and 9 months after delivery.
      They used the Mini International Neuropsychiatric Interview (M.I.N.I.) and the
      Arabic version of Edinburgh Postnatal Depression Scale (EPDS). Using the
      M.I.N.I., 18.7% met DSM-IV criteria for depressive disorder in the second week
      after childbirth. Using a cut-off score of 12, the EPDS indicated a sensitivity
      and specificity of 92% and 96% respectively. Depressive disorder was
      significantly associated with pregnancy complications, stressful life events
      during pregnancy, baby's health problems, and poor marital relationship. The
      subsequent point prevalences were 6.9%, 11.8% and 5.6% respectively at 6 weeks, 6
      and 9 months. Postnatal visits were effective in the identification of Moroccan
      depressed mothers.

PMID- 15868391
TI  - Contribution to the epidemiology of postnatal depression in Germany--implications
      for the utilization of treatment.
AB  - Using a longitudinal screening model, 772 mothers were screened for postnatal
      depression after delivery in Stuttgart (Germany). This model contained the
      Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Depression Scale
      (HAMD). The first screening was 6-8 weeks after delivery with the EPDS. Mothers
      with high scores in the first screening had a second screening 9-12 weeks after
      delivery with the EPDS at least three weeks after the first. Mothers with high
      scores in both screenings were investigated with the Hamilton Depression Scale
      (HAMD). Classification was performed with the DSM-IV. After observation until the
      third month after delivery, 3.6% (N = 28) of the 772 mothers were diagnosed with
      postnatal depression. Various methods of therapy were offered to those mothers.
      18% (N = 5) accepted one or more of these methods of treatment. The rest of the
      mothers with postnatal depression refused--mostly for attitudinal or practical
      reasons. 13.4% of the mothers showed high scores in the first screening but not
      in the second. For those mothers a longitudinal observation is currently being
      performed to distinguish between a depressive episode and a depression with
      oscillating symptoms.

PMID- 15868392
TI  - Infanticide: contrasting views.
AB  - BACKGROUND: The subject of infanticide is met with complex reactions.
      Paradoxically, the very same society that practices gender selection may also
      prosecute a mother for killing an infant. The author reviews historical,
      cultural, and political views on infanticide. OBJECTIVE: Using the case of Andrea
      Yates, the author illustrates the outcome of an infanticide case in American
      Judicial System in which a floridly psychotic mother serves a life in prison.
      This work explores contemporary worldwide experiences of infanticide and
      investigates culture specific attitudes towards causes, facilitation, and
      punishment of this tragic cause of infant mortality. The work illustrates the
      intricate relationship between a society's construction of parenthood and
      mothering, and its experience of infanticide. RESULTS: Infanticide is deeply
      embedded in, and responsive to the societies in which it occurs. Causes vary from
      poverty to stigma, dowry and insanity. The worldwide experience of infant murder
      reaches from facilitation of gender determination in China and Asia to lethal
      execution of mothers as perpetrators in the United States. CONCLUSION:
      Infanticide must be viewed against the political, cultural, social and legal
      backgrounds of societies that treat women with disregard. It is a reflection of
      social and cultural norms governing motherhood, a constant that links these
      seemingly disparate acts. The overall association of infanticide with crime,
      postpartum illness, population and sex selection speaks to unjust discrimination
      against women and children. We as a world society can do a far better job of
      protecting motherhood.

PMID- 15868393
TI  - Reproductive steroids in context.
AB  - The effects of reproductive steroids on the brain are highly context-dependent, a
      concept necessary to understand disorders of mood related to the reproductive
      endocrine system.

PMID- 15868394
TI  - Evidence-based pharmacological treatment of neuropathic pain syndromes.
AB  - Neuropathic pain, caused or initiated by a primary lesion in the peripheral or
      central nervous system, can result in a dramatic reduction in the patient's
      quality of life. The expression neuropathic pain covers a heterogeneous group of
      conditions, including peripheral neuropathy, complex regional pain syndrome,
      trigeminal neuralgia and central pain. Neuropathic pain poorly responds to
      conventional analgesics. However, with appropriate therapy, a significant
      proportion of patients experience a substantial pain reduction. We present here
      an evidence-based review of the options for the treatment of neuropathic pain
      syndromes. Consideration is given to the mechanisms of action, numbers needed to
      treat (NNT), the recommended doses and the most frequent side-effects of the
      drugs for which consistent support has been found for treatment of these pain
      conditions.

PMID- 15868395
TI  - Mass spectrometrical analysis of human serine racemase in foetal brain.
AB  - We analysed human serine racemase for the first time from human foetal brain by
      mass spectrometrical methods, MALDI MS and MS/MS. The detection of human serine
      racemase from a transient area of human foetal brain, the perireticular nucleus,
      that is suggested to be mainly involved in guidance of corticofugal and
      thalamocortical fibers, may be a clue for the important role of this enzyme in
      neuronal migration and brain development via regulation of NMDA receptor
      activity.

PMID- 15868396
TI  - The expanding universe of poly(ADP-ribosyl)ation.

PMID- 15868397
TI  - Introduction to poly(ADP-ribose) metabolism.
AB  - Poly(ADP-ribosyl)ation is a posttranslational modification of proteins in
      eukaryotic cells catalysed by a family of NAD+ ADP-ribosyl transferases, the
      poly(ADP-ribose) polymerases (PARPs). PARP-encoding genes now constitute a
      superfamily of at least 18 members encoding proteins that share homology with the
      catalytic domain of the founding member, PARP-1. Poly(ADP-ribose) metabolism is
      of central importance in a wide variety of biological processes including
      maintenance of genomic stability, DNA repair, transcriptional regulation,
      centromere function, modulation of telomere length, regulation of proteasomal
      protein degradation, regulation of endosomal vesicle trafficking and apoptosis.
      The life cycle of poly(ADP-ribose) is discussed in the following section. In
      addition, an overview of the genes and proteins involved in poly(ADP-ribose)
      metabolism and their possible cellular function is provided.

PMID- 15868398
TI  - Importance of poly(ADP-ribose) polymerases in the regulation of DNA-dependent
      processes.
AB  - Poly(ADP-ribosyl)ation of proteins is involved in the regulation of basal
      cellular processes and seems to be crucial for genomic integrity and cell
      survival. Several nuclear poly(ADP-ribose) polymerases (PARPs) are known which
      interact with various proteins involved in DNA metabolism. These proteins can be
      targets of poly(ADP-ribosyl)ation, which generally downregulates their
      activities. Accordingly, PARPs have been implicated in numerous processes
      involving chromosomal DNA, such as the regulation of chromatin structure, DNA
      repair, replication and transcription. PARP-1, the major cellular PARP, and PARP
      2 are activated by DNA strand breaks. These enzymes have been shown to
      participate in DNA repair. PARP-1 has also been associated with DNA replication
      and recombination. Another outstanding feature of PARP-1 is its impact on the
      activities of transcription factors and on gene expression. Two other nuclear
      PARP enzymes, tankyrase-1 and tankyrase-2, are important for telomere
      maintenance.

PMID- 15868399
TI  - Regulation of poly(ADP-ribose) metabolism by poly(ADP-ribose) glycohydrolase:
      where and when?
AB  - Poly(ADP-ribose) glycohydrolase (PARG) is a catabolic enzyme that cleaves ADP
      ribose polymers formed by members of the PARP family of enzymes. Despite its
      discovery and subsequent partial purification in the 1970s and the cloning of its
      single gene in the late 1990s, little is known about the role of PARG in cell
      function. Because of its low abundance within cells and its extreme sensitivity
      to proteases, PARG has been difficult to study. The existence of several PARG
      isoforms with different subcellular localizations is still debated today after
      more than 30 years of intensive research. In this article, we want to summarize
      and discuss the current knowledge related to PARG, its different forms and
      subcellular distribution. We also examine the possible biological roles of PARG
      in modulating chromatin structure, transcription, DNA repair and apoptosis.

PMID- 15868400
TI  - Pathophysiologic role of oxidative stress-induced poly(ADP-ribose) polymerase-1
      activation: focus on cell death and transcriptional regulation.
AB  - PARP-1 is a nuclear enzyme activated by DNA breaks. Activated PARP-1 cleaves NAD
      into nicotinamide and ADP-ribose and polymerizes the latter covalently coupled to
      nuclear acceptor proteins. Poly(ADP-ribosyl)ation has been implicated in the
      regulation of a diverse array of cellular processes ranging from DNA repair,
      chromatin organization, transcription, replication to protein degradation. On the
      'dark side' of poly(ADP-ribosyl)ation, PARP-1 activation has been shown to
      contribute to tissue injury in shock, diabetes, myocardial or cerebral ischemia
      reperfusion and various forms of inflammation, as proven by pharmacological
      studies as well as experiments utilizing PARP-1 knockout animals. To our current
      knowledge, two mechanisms are responsible for the beneficial effects of PARP
      inhibitors in inflammatory, neurodegenerative and ischemia-reperfusion-based
      diseases: (i) inhibition of cell death caused by over-activation of PARP-1; (ii)
      inhibition of inflammatory signal transduction and production of inflammatory
      mediators. Here we review the possible regulatory mechanisms (e.g. calcium
      signaling, metabolism, density-dependent signaling, kinase cascades) of the PARP
      1-mediated cell death pathway and discuss recent developments shedding new light
      on the complex role of PARP-1 in the regulation of the expression of inflammatory
      mediators.

PMID- 15868401
TI  - Poly(ADP-ribosyl)ation regulation of life and death in the nervous system.
AB  - Poly(ADP-ribosyl)ation is required by multicellular eukaryotes to ensure genomic
      integrity under conditions of mild to moderate genotoxic stress. However, severe
      stress following acute neuronal injury causes overactivation of poly(ADP-ribose)
      polymerase-1, which results in unregulated poly(ADP-ribose) (PAR) synthesis and
      widespread neuronal cell death. Once thought to be a necrotic cell death
      resulting from energy failure, PARP-1 activation is now known to induce the
      nuclear translocation of apoptosis-inducing factor, which results in caspase
      independent cell death. Conversely, poly(ADP-ribose) glycohydrolase, once thought
      to contribute to neuronal injury, now appears to have a protective role as
      demonstrated by recent studies utilizing gene disruption technology. Thus, the
      emerging mechanism dictating the fate of neurons appears to involve the
      regulation of PAR levels in neurons. Therefore, therapies targeting poly(ADP
      ribosyl)ation in the treatment of neurodegenerative conditions such as stroke and
      Parkinson's disease are required to inhibit PAR synthesis and/or facilitate its
      degradation.

PMID- 15868402
TI  - Poly(ADP-ribosyl)ation in relation to cancer and autoimmune disease.
AB  - Carcinogenesis involves multiple steps and pathways with functional alterations
      in a variety of genes. There is accumulating evidence that a deficiency of
      poly(ADP-ribose) polymerase (PARP)-1 leads to DNA repair defects, genomic
      instability, failure of induction of cell death and modulation of gene
      transcription. PARP-1 also supports the growth of tumor cells in certain
      situations. Genetic analyses of the PARP-1 gene have demonstrated alterations in
      neoplasms, and a mutation affecting the conserved amino acid E251 in germ cell
      tumors, as well as an association of a single-nucleotide polymorphism V762A with
      risk of prostate cancer. Recent development of a selective inhibitor of poly(ADP
      ribose) glycohydrolase (PARG), the enzyme primarily responsible for degradation
      of poly(ADP-ribose), and PARG-deficient animals should facilitate studies of the
      relationship of poly(ADP-ribose) with carcinogenesis. Inhibitors of PARP have
      also suggested roles in the pathogenesis of autoimmune disease, and a promoter
      haplotype of PARP-1 confers a higher risk of rheumatoid arthritis. Further
      analysis of PARP-1, PARG and other PARP family genes should extend our
      understanding of the pathogenesis of cancer and autoimmune diseases. Furthermore,
      there is potential for sensitization to chemo- and radiation therapy of cancers
      as well as the treatment of autoimmune disease with development of stronger PARP
      inhibitors.

PMID- 15868403
TI  - Host defense peptides as new weapons in cancer treatment.
AB  - In the last decade intensive research has been conducted to determine the role of
      innate immunity host defense peptides (also termed antimicrobial peptides) in the
      killing of prokaryotic and eukaryotic cells. Many antimicrobial peptides damage
      the cellular membrane as part of their killing mechanism. However, it is not
      clear what makes cancer cells more susceptible to some of these peptides, and
      what the molecular mechanisms underlying these activities are. Two general
      mechanisms were suggested: (i) plasma membrane disruption via micellization or
      pore formation, and (ii) induction of apoptosis via mitochondrial membrane
      disruption. To be clinically used, these peptides need to combine high and
      specific anticancer activity with stability in serum. Although so far very
      limited, new studies have paved the way for promising anticancer host defense
      peptides with a new mode of action and with a broad spectrum of anticancer
      activity.

PMID- 15868404
TI  - Mechanisms underlying celiac disease and its neurologic manifestations.
AB  - The extra-intestinal manifestations of celiac disease (CD), including ataxia and
      peripheral neuropathy, are increasingly being recognized as the presenting
      symptoms of this autoimmune disease. Although there is a greater understanding of
      the pathogenesis of the intestinal lesions in CD the mechanisms behind the
      neurologic manifestations of CD have not been elucidated. In this article, the
      authors review the cellular and molecular mechanisms behind the histopathologic
      changes in the intestine, discuss the presentation and characteristics of
      neurologic manifestations of CD, review the data on the mechanisms behind these
      manifestations, and discuss the diagnosis and treatment of CD. Molecular mimicry
      and intermolecular help may play a role in the development of neurologic
      complications.

PMID- 15868405
TI  - A genetic perspective on myopia.
AB  - Myopia is a refractive error of the eye that has a significant socioeconomic
      impact due to its increasing prevalence and the fact that it causes visual
      impairment. Its aetiology is complex and is likely to involve the interaction of
      environmental and genetic influences. Tight environmental influence is
      exemplified by defocus-induced myopia produced in animal models, while genetic
      factors predominate in familial occurrence of myopia with a Mendelian inheritance
      pattern. The involvement of numerous mediators, such as cytokines,
      neurotransmitters and transcription factors, in myopia development has been
      indicated through various lines of investigation, particular interest focussing
      on scleral extracellular matrix proteins and developmental genes of the eye. As
      high-throughput technology for large-scale genotyping and RNA expression analysis
      enters the field of myopia research, a productive avenue will open up for
      deciphering the aetiological heterogeneity of myopia and the biological pathways
      underlying its development.

PMID- 15868406
TI  - Congenital muscular dystrophy: molecular and cellular aspects.
AB  - The congenital muscular dystrophies are a clinically and genetically
      heterogeneous group of neuromuscular disorders. Each form has a characteristic
      phenotype, but there is overlap between some entities and their classification is
      based on a combination of clinical features and the primary or secondary protein
      defect. Recent studies have identified the genetic basis of a number of
      congenital muscular dystrophies (11 genes in total) and have recognised a novel
      pathological mechanism that highlights the importance of the correct
      posttranslational processing of proteins, in particular alpha-dystroglycan.
      Diagnosis of these conditions has been aided by the availability of specific
      antibodies for each protein and a better understanding of the protein changes
      that accompany each condition. In this review we present the major molecular,
      clinical and diagnostic aspects of each group of congenital muscular dystrophy
      with an emphasis in the more recent developments.

PMID- 15868407
TI  - Aspects of gene polymorphisms in cerebral infarction: inflammatory cytokines.
AB  - During the last decade, a growing corpus of evidence has indicated an important
      role of inflammatory cytokines in the pathogenesis of cerebral lesion following
      stroke. Recent data suggest that genetics may in turn contribute to modulating
      the effects of inflammatory cytokines on cerebral infarction (CI). This paper
      reviews the physiologic characteristics of major inflammatory cytokines and
      recent research developments related to cell biology and pathobiology in CI. In
      particular, this review focuses on the genetic aspects of inflammatory cytokines
      and their implications in CI.

PMID- 15868408
TI  - Thiyl radicals in biosystems: effects on lipid structures and metabolisms.
AB  - Thiyl radicals are intermediates of enzyme- and radical-driven biochemical
      processes, and their potential as reactive species in the biological environment
      has been somehow underestimated. From organic chemistry, however, it is known
      that thiyl radicals isomerize the double bonds of unsaturated fatty acids to a
      mixture with very dominating trans isomers. Recently, this reaction has been
      particularly studied for biosystems, focusing on the effect of thiyl radicals on
      the natural all-cis double bonds of unsaturated phospholipids, which undergo a
      conversion to the unnatural trans form. In this paper we report briefly the role
      of thiyl radicals in biosystems, describe the main features of the radical
      induced cis-trans isomerization process under both in vitro and in vivo
      conditions, and reflect on some consequences for membrane structures, lipid
      metabolism and enzymatic reactions.

PMID- 15868409
TI  - Mass spectrometry-based proteomics in the life sciences.
AB  - Over the last 20 years, mass spectrometry-based proteomics has become an
      indispensable tool in the cellular and molecular life sciences. This has been
      enabled by the 'soft ionisation' techniques of electrospray and matrix-assisted
      laser desorption-ionisation, which allow the gentle ionisation and vaporisation
      of large, thermally labile biomolecules. Innovative instrumentation designs and
      biochemical strategies have brought success in the large-scale identification and
      quantification of proteins, as well as the characterisation of their complexes
      and post-translational modifications. This review describes the instrumentation
      used for proteomics research. It presents an overview of the current applications
      of mass spectrometry-based proteomics to the cellular and molecular life
      sciences, and discusses challenges that exist for research in the future.

PMID- 15868410
TI  - Matrix metalloproteinase 19 processes the laminin 5 gamma 2 chain and induces
      epithelial cell migration.
AB  - In this study we analyzed the proteolytic activity of MMP-19 and its impact on
      keratinocyte migration. In the HaCaT keratinocyte cell line overexpressing wild
      type MMP-19 (HaCaT-WT), transmigration through fibrin and type IV collagen
      matrices was significantly increased compared to cells harboring a catalytically
      inactive mutant (HaCaT-EA). Studying the expression of MMP-19 in early stages of
      squamous cell cancer (SCC), we found co-localization of MMP-19 and laminin 5 at
      the invading tumor front but not in suprabasal epidermis of the tumor.
      Examination of laminin 5 processing revealed increased processing of the gamma2
      chain in the medium and matrix of HaCaT-WT cells and degradation by recombinant
      human MMP-19 to 105-kDa and 80-kDa fragments. Parental HaCaT grown on the matrix
      of HaCaT-WT and HaCaT-EA cells displayed differential tyrosine phosphorylation.
      Using integrin blocking and stimulating antibodies we could attribute these
      differences to a shift from beta4-integrin-dependent signaling on the HaCaT-EA
      matrix toward alpha3-integrin-dependent signaling on the HaCaT-WT matrix. As a
      consequence, parental HaCaT showed increased migration on the matrix of HaCaT-WT
      cells. These data suggest that the MMP-19-dependent processing of the gamma2
      chains leads to the integrin switch favoring epithelial migration and that MMP-19
      actively participates in the early stages of SCC invasion.

PMID- 15868411
TI  - Antitumor effect of beta-elemene in non-small-cell lung cancer cells is mediated
      via induction of cell cycle arrest and apoptotic cell death.
AB  - Beta-elemene is a novel anticancer drug, which was extracted from the ginger
      plant. However, the mechanism of action of beta-elemene in non-small-cell lung
      cancer (NSCLC) remains unknown. Here we show that beta-elemene had differential
      inhibitory effects on cell growth between NSCLC cell lines and lung fibroblast
      and bronchial epithelial cell lines. In addition, beta-elemene was found to
      arrest NSCLC cells at G2-M phase, the arrest being accompanied by decreases in
      the levels of cyclin B1 and phospho-Cdc2 (Thr-161) and increases in the levels of
      p27(kip1) and phospho-Cdc2 (Tyr-15). Moreover, beta-elemene reduced the
      expression of Cdc25C, which dephosphorylates/activates Cdc2, but enhanced the
      expression of the checkpoint kinase, Chk2, which phosphorylates/ inactivates
      Cdc25C. These findings suggest that the effect of beta-elemene on G2-M arrest in
      NSCLC cells is mediated partly by a Chk2-dependent mechanism. We also demonstrate
      that beta-elemene triggered apoptosis in NSCLC cells. Our results clearly show
      that beta-elemene induced caspase-3, -7 and -9 activities, decreased Bcl-2
      expression, caused cytochrome c release and increased the levels of cleaved
      caspase-9 and poly(ADP-ribose) polymerase in NSCLC cells. These data indicate
      that the effect of beta-elemene on lung cancer cell death may be through a
      mitochondrial release of the cytochrome c-mediated apoptotic pathway.

PMID- 15868412
TI  - Antiproliferative effect of beta-elemene in chemoresistant ovarian carcinoma
      cells is mediated through arrest of the cell cycle at the G2-M phase.
AB  - Elemene is a natural antitumor plant drug. However, the effect of elemene on cell
      growth in ovarian cancer is unknown. In this study, we show that beta-elemene
      inhibited the proliferation of cisplatin-resistant human ovarian cancer cells and
      their parental cells, but had only a marginal effect in human ovary cells,
      indicating differential inhibitory effects on cell growth between ovarian cancer
      cells and normal ovary cells. We also demonstrated for the first time that beta
      elemene markedly enhanced cisplatin-induced growth inhibition in resistant cells
      compared to sensitive cells. In addition, cell cycle analysis revealed a
      synergistic effect of beta-elemene and cisplatin on the induction of cell cycle
      G2-M arrest in our resistant ovarian carcinoma cells. Furthermore, we showed that
      treatment of these cells with both drugs downregulated cyclin B1 and Cdc2
      expression, but elevated the levels of p53, p21waf1/cip1, p27kip1 and Gadd45.
      Finally, the combination of beta-elemene and cisplatin was found to increase the
      phosphorylation of Cdc2 and Cdc25C, which leads to a reduction in Cdc2-cyclin B1
      activity. These novel findings suggest that beta-elemene sensitizes
      chemoresistant ovarian carcinoma cells to cisplatin-induced growth suppression
      partly through modulating the cell cycle G2 checkpoint and inducing cell cycle G2
      M arrest, which lead to blockade of cell cycle progression.

PMID- 15868413
TI  - Functional expression of mammalian opioid receptors in insect cells and high
      throughput screening platforms for receptor ligand mimetics.
AB  - Lepidopteran cell lines have been engineered to constitutively express high
      levels of mouse delta opioid receptors either alone or in combination with human
      Galpha16 protein. Biochemical and pharmacological studies demonstrate that these
      lines contain all the mediator G proteins and downstream effectors required for
      opioid receptor function, including phospholipase C, and that expression of
      exogenous Galpha16 does not contribute significantly to increased receptor
      responses upon activation. The activation of the phospholipase C pathway in the
      transformed cells upon stimulation with known receptor ligands results in easily
      and quantitatively measurable increases in free intracellular calcium, which can
      be monitored by automated fluorescent methods, while the addition of specific
      antagonists blocks the agonist-induced responses. Therefore, the transformed
      lepidopteran cell lines can be used as sensitive high-throughput screening
      platforms for fast detection of delta opioid receptor ligand mimetics (agonists
      and antagonists) in collections of natural products and synthetic compounds.

PMID- 15868417
TI  - Elucidating genetic diversity with oligonucleotide arrays.
AB  - DNA microarrays, initially designed to measure gene expression levels, also
      provide an ideal platform for determining genetic diversity. Oligonucleotide
      microarrays, predominantly high-density oligonucleotide arrays, have emerged as
      the principal platforms for performing genome-wide diversity analysis. They have
      wide-ranging potential applications including comparative genomics, polymorphism
      discovery and genotyping. The identification of inheritable genetic markers also
      permits the analysis of quantitative traits, population studies and linkage
      analysis. In this review, we will discuss the application of oligonucleotide
      arrays, in particular high-density oligonucleotide arrays for elucidating genetic
      diversity and highlight some of the directions that the field may take.

PMID- 15868418
TI  - Array CGH technologies and their applications to cancer genomes.
AB  - Cancer is a disease characterized by genomic instability. Comparative genomic
      hybridization (CGH) is a technique designed for detecting segmental genomic
      alterations. Recent advances in array-based CGH technology have enabled
      examination of chromosomal regions in unprecedented detail, revolutionizing our
      understanding of tumour genomes. A number of array-based technologies have been
      developed, aiming to improve the resolution of CGH, enabling researchers to
      refine and define regions in the genome that may be causal to cancer, and
      facilitating gene discovery at a rapid rate. This article reviews the various
      array CGH platforms and their use in the study of cancer genomes. In addition,
      the need for high-resolution analysis is discussed as well as the importance of
      studying early-stage disease to discover genetic alterations that may be causal
      to cancer progression and aetiology.

PMID- 15868419
TI  - Investigating chromosome organization with genomic microarrays.
AB  - DNA microarrays are increasingly being used to investigate the functional role of
      chromatin. These studies are enhanced by the development of high-resolution
      arrays covering either the whole genome or specific regions of selected
      chromosomes with large insert clones, PCR products or oligonucleotides of around
      100 bp or less. In combination with chromatin immunoprecipitation, this approach
      allows identification of protein binding for transcription factors, proteins
      involved in DNA replication and repair as well as sites of chromatin
      modification. Furthermore, by application of S phase fractions to genomic
      microarrays, replication timing can be estimated. Thus, microarrays can provide
      new information about chromosome structure and gene regulation.

PMID- 15868420
TI  - Applications of DNA tiling arrays to experimental genome annotation and
      regulatory pathway discovery.
AB  - Microarrays have become a popular and important technology for surveying global
      patterns in gene expression and regulation. A number of innovative experiments
      have extended microarray applications beyond the measurement of mRNA expression
      levels, in order to uncover aspects of large-scale chromosome function and
      dynamics. This has been made possible due to the recent development of tiling
      arrays, where all non-repetitive DNA comprising a chromosome or locus is
      represented at various sequence resolutions. Since tiling arrays are designed to
      contain the entire DNA sequence without prior consultation of existing gene
      annotation, they enable the discovery of novel transcribed sequences and
      regulatory elements through the unbiased interrogation of genomic loci. The
      implementation of such methods for the global analysis of large eukaryotic
      genomes presents significant technical challenges. Nonetheless, tiling arrays are
      expected to become instrumental for the genome-wide identification and
      characterization of functional elements. Combined with computational methods to
      relate these data and map the complex interactions of transcriptional regulators,
      tiling array experiments can provide insight toward a more comprehensive
      understanding of fundamental molecular and cellular processes.

PMID- 15868421
TI  - Devising transcriptional regulatory networks operating during the cell cycle and
      differentiation using ChIP-on-chip.
AB  - The study of global transcriptional regulatory networks in eukaryotes has
      advanced rapidly in the last five years with the advent of genomic microarrays
      that allow investigators to comprehensively scrutinize the structure and
      composition of transcriptomes and chromatin. Many facets of this field have
      benefited from an examination of the location of proteins associated with
      chromatin. We describe here how we have used genomic arrays to perform location
      analysis (or ChIP-on-chip analysis) of regulatory factors that control the
      complex process of cell cycle progression and differentiation, in order to
      identify key direct transcriptional targets. Combining this information with data
      obtained through expression profiling and computational analysis of transcription
      factor binding sites has also allowed us to devise transcriptional regulatory
      networks governing these processes.

PMID- 15868422
TI  - Whole-genome views of chromatin structure.
AB  - DNA in eukaryotes is packed into chromatin. The basic component of chromatin is
      the nucleosome consisting of DNA wrapped around a histone octamer. Inside the
      cell nucleus, chromatin is folded into higher-order structures through various
      mechanisms, including repositioning of nucleosomes along the DNA, packing of
      nucleosomes into more condensed 3-dimensional configurations, looping of
      chromatin fibres, and tethering of chromosomal regions to nuclear structures.
      Over the past few years, new microarray-based methods have been developed for the
      genome-wide mapping of various aspects of chromatin structure. These methods are
      beginning to provide insights into the different types of chromatin and the
      architectural principles that govern the 3-dimensional organisation of the genome
      inside the nucleus.

PMID- 15868423
TI  - Epigenomic mapping in Arabidopsis using tiling microarrays.
AB  - In addition to genetic information, chromosomes transmit epigenetic information
      from cell to cell during division, and sometimes from generation to generation.
      While genetic information is encoded directly in the DNA sequence, epigenetic
      information is not, although it is usually associated with specific chromosomal
      regions. Epigenetic modifications in plants include cytosine methylation as well
      as modification of histones and other chromosomal proteins. Small interfering RNA
      play major roles in targeting these modifications to specific regions. Genomic
      tiling microarrays are powerful tools for analysing epigenetic information, and
      we review their application in building epigenomic maps in the model plant,
      Arabidopsis.

PMID- 15868424
TI  - A genomic view of eukaryotic DNA replication.
AB  - Recent advances in DNA microarray technology have enabled eukaryotic replication
      to be studied at whole-chromosome and genome-wide levels. These studies have
      provided new insights into the mechanisms that influence origin selection and the
      temporally co-ordinated activation of replication initiation from these sites.
      Here we describe multiple microarray-based approaches that have been used to
      study DNA replication in both S. cerevisiae and higher eukaryotes. We have also
      compiled the data from the yeast microarray-based replication studies to generate
      a comprehensive list of origins that has been verified in three independent
      studies. The comprehensive nature of the microarray-based studies has revealed
      clear connections between chromosome organization and the pattern of replication.
      For example, in yeast, the centromeric proximal sequences are consistently early
      replicating and telomeric regions are consistently late replicating. The metazoan
      studies reveal a recurring theme of gene-dense transcriptionally active regions
      of the genome replicating before gene-sparse regions. In addition to the insights
      they have provided already, microarray-based replication assays combined with
      genetic analysis will provide a powerful new approach to define the mechanisms
      that regulate replication origin function.

PMID- 15868425
TI  - Post-transcriptional operons and regulons co-ordinating gene expression.
AB  - Experiments reported over the past several years, including genome-wide
      microarray approaches, have demonstrated that many eukaryotic RNA-binding
      proteins (RBPs) associate with multiple messenger RNAs (mRNAs) both in vitro and
      in vivo. This multi-targeted binding property of RBPs has led to a model of
      regulated gene expression in eukaryotes that we termed the post-transcriptional
      operon. This concept was established by an analogy between polycistronic mRNAs
      that are generated from bacterial operons, and the co-ordinated regulation of
      multiple monocistronic mRNAs by RBPs. Post-transcriptional operons represent a
      powerful mechanism to organize and express genetic information as functionally
      related combinations of monocistronic mRNAs. In fact, much of the diversification
      of individual proteomes may be determined by the combinatorial properties of post
      transcriptional operons. This review examines data supporting the role of post
      transcriptional operons and regulons in organizing genetic information and co
      ordinating expression of functionally related transcripts from their origins at
      transcription to their subsequent splicing, export and translation.

PMID- 15868426
TI  - Role of dynamic contrast enhanced MRI in monitoring early response of locally
      advanced breast cancer to neoadjuvant chemotherapy.
AB  - Neoadjuvant chemotherapy has become the standard treatment for patients with
      locally advanced breast cancer; however a technique that can accurately
      differentiate responders from non-responders at an early time point during
      treatment has still to be identified. The purpose of this work was to evaluate
      the ability of pharmacokinetically modelled dynamic contrast-enhanced MRI data to
      predict and monitor response of patients diagnosed with locally advanced breast
      cancer to neoadjuvant chemotherapy, at an early time point during treatment.
      Sixty-eight patients with histology proven breast cancer underwent MRI
      examination prior to treatment, early during treatment and following the final
      cycle of chemotherapy. A two compartment pharmacokinetic model provided the
      kinetic parameters transfer constant (Ktrans), rate constant (Kep) and
      extracellular extravascular space (Ve) for a region of interest encompassing the
      whole lesion (ROIwhole) and a 3x3 pixel 'hot-spot' showing the greatest mean
      maximum percentage enhancement from within that region (ROIhs). Following
      treatment 48 patients were classified as responders and 20 as non-responders
      based on total tumour volume reduction. Tumour volume changes between the pre
      treatment and early treatment time points demonstrated differences between
      responders and non-responders with percentage change revealing the most
      significant result (p<0.001). Analysis based on ROIhs provided more statistically
      significant differences between responders and non-responders then ROIwhole
      analysis. ROIhs analysis demonstrated differences between responders and non
      responders both prior to and early during treatment. A highly significant
      reduction in both Ktrans and Kep (p<0.001) was noted for responders between the
      pre-treatment and early treatment time points, while Ve significantly increased
      during the same time period for non-responders (p<0.001). Quantification of
      dynamic contrast enhancement parameters provides a potential means for
      differentiating responders from non-responders early during their treatment,
      thereby allowing a prompt change in treatment if necessary.

PMID- 15868427
TI  - Effect of axillary lymphadenectomy on breast carcinoma survival.
AB  - PURPOSE: To determine the effect of axillary lymphadenectomy on breast carcinoma
      survival, and to determine racial and age differences in the extent of axillary
      lymphadenectomy. METHODS: Cases were 257,157 women diagnosed with breast
      carcinoma in the Surveillance, Epidemiology and End Results program from 1988
      through 2000. Variables included number of lymph nodes removed, number of
      positive lymph nodes, ratio of positive nodes to number of nodes removed, use of
      radiation therapy, surgery (breast conserving surgery versus mastectomy), stage,
      age, race, and hormone receptor status. Correlation statistics were used to
      determine associations between survival and lymph node variables for all cases
      and when stratified by stage. Kaplan-Meier survival analyses were used to compare
      survival by lymph node categories overall and stratified by stage. Cox regression
      analyses were used to determine factors associated with survival. RESULTS: Older
      women were significantly less likely to have lymph nodes examined and lymph node
      involvement compared to younger women, and black women were significantly less
      likely to have lymph nodes examined, but were significantly more likely to have
      lymph node involvement compared to white women. Risk of death was significantly
      reduced for cases who had lymphadenectomy compared to those who did not. For
      cases diagnosed at stage IIA or higher, risk of death increased significantly
      with increased number of positive nodes and increased ratio of positive to total
      nodes removed. CONCLUSIONS: Improved survival in node negative cases of breast
      carcinoma may be due to removal of undetected micrometastases. Women diagnosed at
      more advanced stages as well as black women may also benefit from more extensive
      lymphadenectomy.

PMID- 15868428
TI  - Prevention of metastases with a Mage-b DNA vaccine in a mouse breast tumor model:
      potential for breast cancer therapy.
AB  - Anti-tumor vaccines are a relatively non-toxic alternative to conventional
      chemotherapeutic strategies to control breast cancer. Immunization with tumor
      associated antigens (TAAs) triggers anti-tumor cytotoxic T lymphocytes (CTL),
      which can limit tumor progression. Here we report on the development and
      effectiveness of a TAA-based DNA vaccine encoding Mage-b1/2, the mouse homologue
      of the human MAGE-B1/2. As model system, we used immune competent Balb/c mice
      with syngeneic non-metastatic (64pT) or metastatic (4TO7cg) breast tumors. First,
      the presence of Mage-btranscripts in the 64pT and 4TO7cg breast tumors and
      metastases was demonstrated by RT-PCR, Southern blotting, and DNA sequencing. A
      DNA-based vaccine was developed from transcripts of one of the 64pT tumors,
      encoding the complete Mage-b1/2 protein, and subsequently tested for its
      preventive efficacy in both breast tumor models. Mice were immunized two times
      intramuscularly with the vaccine (pcDNA3.1-Mage-b1/2-V5), the control vector
      (pcDNA3.1-V5), or saline. Two weeks after the last immunization, the syngeneic
      4TO7cg or 64pT tumor cell lines were injected in a mammary fat pad. Mice were
      monitored during the next 4 weeks for tumor formation, latency and size, and
      subsequently sacrificed for analysis. While the Mage-b1/2 vaccine had only a
      minor effect on the latency and growth of primary tumors, a significant and
      reproducible reduction in the number of 4TO7cg metastases was observed (vaccine
      versus control vector, p=0.0329; vaccine versus saline, p=0.0128). The observed
      protective efficacy of the Mage-b DNA vaccine correlated with high levels of
      vaccine-induced IFNgamma in spleen and lymph nodes upon re-stimulation in vitro.
      These results demonstrate the potential of TAA-based DNA vaccines in controlling
      metastatic disease in breast cancer patients.

PMID- 15868429
TI  - Effect of perductal paclitaxel exposure on the development of MNU-induced mammary
      carcinoma in female S-D rats.
AB  - BACKGROUND: Breast carcinoma and precancer are thought to start in the lining of
      the milk duct or lobule. METHODS: At 5weeks of age, rats received a
      intraperitoneal (ip) injection of MNU for carcinogenesis. After mammary tumors
      were identified macroscopically using fiberscope, the rats were treated with
      perductal (pd) or ip injection of paclitaxel tri-weekly. At 36 weeks after MNU
      injection, tumor burden (No. of >1cm palpable mammary tumors/rat), total number
      of mammary carcinoma, apoptosis (AI), and microvessel density (MVD) were
      measured. RESULTS: The administration of paclitaxel through the duct did not
      produce any toxic side effect. The tumor burden and total number of mammary
      carcinoma in the pd paclitaxel-treated group were significantly reduced compared
      to those seen in the ip paclitaxel-treated group. In addition, in the pd
      paclitaxel-treated group, AI was also increased and MVD was decreased, compared
      to those in the ip paclitaxel-treated group. CONCLUSION: Local administration of
      paclitaxel may be useful for treatment of breast cancer.

PMID- 15868430
TI  - Inositol hexaphosphate (IP6) blocks proliferation of human breast cancer cells
      through a PKCdelta-dependent increase in p27Kip1 and decrease in retinoblastoma
      protein (pRb) phosphorylation.
AB  - Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated
      carbohydrate with demonstrated anti-proliferative and anti-cancer activity in
      mammary cells. We hypothesized that IP6 modulates cell cycle proteins by action
      on cytoplasmic signaling molecules. The effects of both pharmacological (2 mM)
      and physiological (100 microM) doses of IP6 on major PKC isoforms (PKCalpha,
      delta, epsilon, beta and zeta), PI3-K/Akt and ras/Erk1/2 were evaluated.
      Treatment of MCF-7 human breast cancer cells with 2 mM IP6 for 24 h caused a 3.1
      fold increase in the expression of anti-proliferative PKCdelta. Similar results
      were observed with 100 microM IP6 at only 30-60 min post-treatment. IP6 also
      caused an increase in PKCdelta activity, shown by its translocation from cytosol
      to membrane. No changes in expression of PKC alpha, delta, epsilon, beta and zeta
      were detected. Additionally, IP6 caused a decrease of Erk1/2 and Akt activity.
      Among cell cycle control proteins, IP6 resulted in increased p27Kip1 protein
      levels and marked reduction of pRb phosphorylation. Specificity of the IP6
      effects on p27Kip1 and pRb in MCF-7 cells (hormone-dependent) were additionally
      confirmed in highly invasive hormone-independent MDA-MB 231 breast cancer cells.
      Use of specific pharmaclogical inhibitors of PKC delta, MEK/Erk, and PI3K/Akt
      pathways indicated that the IP6-mediated effects on PKC delta were responsible
      for up-regulation of p27Kip, and pRb hypo-phosphorylation. In addition, IP6
      induced apoptosis detected in MCF-7 cells appeared also to be PKC delta
      dependent. Our data suggest potential usefulness of IP6 as a novel therapeutic
      modulator of PKC delta and p27Kip1, an important prognostic factor in human
      breast cancers.

PMID- 15868431
TI  - Daily coordination of cancer growth and circadian clock gene expression.
AB  - BACKGROUND: Circadian coordination in mammals is accomplished, in part, by
      coordinate, rhythmic expression of a series of circadian clock genes in the
      central clock within the suprachiasmatic nuclei (SCN) of the hypothalamus. These
      same genes are also rhythmically expressed each day within each peripheral
      tissue. METHODS: We measured tumor size, tumor cell cyclin E protein, tumor cell
      mitotic index, and circadian clock gene expression in liver and tumor cells at
      six equispaced times of day in individual mice of a 12-h light, 12-h dark
      schedule. RESULTS: We demonstrate that C3HFeJ/HeB mice with transplanted
      syngeneic mammary tumor maintain largely normal circadian sleep/activity
      patterns, and that the rate of tumor growth is highly rhythmic during each day.
      Two daily 2.5-fold peaks in cancer cell cyclin E protein, a marker of DNA
      synthesis, are followed by two daily up-to-3-fold peaks in cancer cell mitosis
      (one minor, and one major peak). These peaks are, in turn, followed by two
      prominent daily peaks in tumor growth rate occurring during mid-sleep and the
      second, during mid-activity. These data indicate that all therapeutic targets
      relevant to tumor growth and tumor cell proliferation are ordered in tumor cells
      within each day. The daily expression patterns of the circadian clock genes
      Bmal1, mPer1, and mPer2, remain normally circadian coordinated in the livers of
      these tumor bearing mice. Bmal1 gene expression remains circadian rhythmic in
      cancer cells, although damped in amplitude, with a similar circadian pattern to
      that in normal hepatocytes. However, tumor cell mPer1 and mPer2 gene expression
      patterns fail to maintain statistically significant daily rhythms. CONCLUSION: We
      conclude that, if core circadian clock gene expression is essential to gate tumor
      cell proliferation within each day, then there may be substantial redundancy in
      this timing system. Alternatively, the daily ordering of tumor cell clock gene
      expression may not be essential to the daily gating of cancer cell DNA synthesis,
      mitosis and growth. This would indicate that host central SCN-mediated neuro
      humoro-behavioral controls and/or daily light-induced changes in melatonin or
      peripherally-induced rhythms such as those resulting from feeding, may be
      adequate for the daily coordination of cancer cell expression of proliferation
      related therapeutic targets.

PMID- 15868432
TI  - Combined flow cytometry determination of S-phase fraction and DNA ploidy is an
      independent prognostic factor in node-negative invasive breast carcinoma:
      analysis of a series of 271 patients with stage I and II breast cancer.
AB  - PURPOSE: To assess the significance of S-phase fraction (SPF) and DNA ploidy
      evaluated by DNA flow cytometry as prognostic markers in stage I or II breast
      cancer. PATIENTS AND METHODS: A series of 271 patients, treated by surgery,
      radiotherapy +/- systemic therapy was analyzed (median follow up: 64 months).
      Standardized flow cytometry cell preparation from frozen samples and consensus
      rules for data interpretation were followed. Three SPF classes were defined on
      the basis of tertiles after adjustment for ploidy. Four groups were defined based
      on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and
      low SPF (DL, n=37), DIP and medium or high SPF (DMH, n=76), ANEUP and low SPF
      (AL, n=24), ANEUP and medium or high SPF (AMH, n=68). Local control rate (LCR),
      disease-free survival (DFS), metastasis-free survival (MFS), and overall survival
      (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR
      grading, age, and hormonal status on univariate and multivariate analysis (Cox
      model). RESULTS: On univariate analysis, DFS and LCR were higher for DIP tumours.
      High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates
      were significantly different with an increasingly poorer prognosis from DL to
      AMH. On multivariate analysis, groups DL to AMH, histological node involvement
      and T stage were independently associated with MFS, and DFS. In N- patients, DL
      to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were
      significantly different in DL to AMH groups. These results strongly support the
      use of combined evaluation of DNA ploidy and SPF as independent parameters in
      clinical trials for N- stage I and II breast cancer.

PMID- 15868433
TI  - MTHFR genotypes and breast cancer survival after surgery and chemotherapy: a
      report from the Shanghai Breast Cancer Study.
AB  - Methylenetetrahydrofolate reductase (MTHFR) regulates the intracellular folates
      pool for DNA synthesis and methylation. Sequence variations in MTHFR (nucleotides
      677 (C-->T) and 1298 (A-->C)) result in allozymes with decreased activity. The
      677TT genotype is associated with increased toxicity of methotrexate and
      increased clinical response to 5-fluorouracil in treatment of cancers including
      breast cancer. We evaluated MTHFR genotypes and breast cancer survival in a
      cohort of 1067 Chinese women diagnosed with breast cancer between 1996 and 1998
      who received surgery and chemotherapy. Life table method was used to calculate 5
      year survival rates. Cox proportional hazards models were used to estimate hazard
      ratios (HR) and 95% confidence intervals (CI) after adjusting for potential
      confounding factors. Median follow-up time was 5.2 years; 5-year survival was
      84.6%. Sixty-six percent carried a 677T allele and 31% carried a 1298 C allele.
      We found that overall 5-year breast cancer survival did not differ significantly
      across all genotypes (85.3% for 677 CC and 83.8% for 677TT; 83.8% for 1298 AA and
      79.1% for 1298 CC). However, carrying the 677T allele was associated with non
      significant increased risk of death for subjects with late stage disease (stages
      III-IV) (HR=1.80, 95% CI: 0.79-4.14 for TT vs. CC, p for trend=0.15),
      particularly among those who had survived past the second year (HR=2.97, 95% CI:
      1.10-7.98, p for trend=0.04). The A1298C genotypes were not significantly
      associated with risk of death. This study suggests that the MTHFR C677T
      polymorphisms may affect long-term survival from advanced breast cancer.

PMID- 15868434
TI  - Association between HER-2/neu and the progesterone receptor in oestrogen
      dependent breast cancer is age-related.
AB  - In oestrogen receptor-positive (ER+) breast cancer, HER-2/neu and the
      progesterone receptor (PR) are inversely associated. This explains a lower
      response to anti-oestrogens if ER+ breast cancers are HER-2/neu positive. One
      randomized study however, showed that premenopausal women with an ER+ breast
      cancer respond to anti-oestrogens independent of HER-2/neu. We therefore
      hypothesized an age-related association between HER-2/neu and PR in ER+ breast
      cancers. Receptors for ER, PR and HER-2/neu were analysed by immunohistochemistry
      (IHC). A uni- and multivariate analyses was carried out to assess this
      relationship in 1104 women with an ER+ breast cancer. We observed an inverse
      association between HER-2/neu and PR only after age 45. There were 173 women of
      age<or=45 and 931 of age>45 years. In multivariate analysis, only tumour grade
      (p=0.005) but not PR status was associated with HER-2/neu in women age<or=45
      years. However, in age>45 years group, both PR status (p=0.001) and tumour grade
      (p=0.001) were independently associated with HER-2/neu. In ER+ breast cancers
      from women age>45, PR was positive in 76.9% if HER-2/neu negative but in 53.4% if
      HER-2/neu positive (p<0.001) and the median quantitative PR levels are 150 and 75
      respectively in HER-2/neu negative and HER-2/neu positive tumours (p=0.002). This
      age effect of HER-2/neu on the PR status was not seen in women age<or=45 years
      and the median quantitative PR levels are 200 and 220 respectively in HER-2/neu
      negative and HER-2/neu positive tumours (p=0.518). The study confirms an age
      related inverse relationship between HER-2/neu and PR only in women age>45 years
      but not in women age<or=45 years.

PMID- 15868435
TI  - Detection of genetic instability at HER-2/neu and p53 loci in breast cancer cells
      sing Comet-FISH.
AB  - A proportion of breast cancers acquire genetic alterations at 17q11.2-q12 (HER
      2/neu), 20q13.2 (ZNF217 gene) and 17p13.1 (p53). We describe a unique technique
      (Comet-FISH) in which we documented relative genetic instability at p53 and HER
      2/neu gene loci within a panel of malignant breast cancer cell lines (MCF-7; MDA
      MB-468 and CRL-2336). Furthermore, Comet-FISH data were consistent with
      preferential repair of the p53 locus following gentoxic insult and suggest that
      this assay may be quite useful for the study of genetic instability.

PMID- 15868436
TI  - Sex cycle modulates cancer growth.
AB  - HYPOTHESIS: Among premenopausal women, both post-resection metastatic potential
      and tumor growth rate are influenced by the menstrual cycle. There is strong
      support for the former in large retrospective studies of surgical resection
      timing within the menstrual cycle and the following experiments were conducted to
      critically evaluate the latter. METHODS: We studied a transplantable breast
      cancer of C3HeB/FeJ mice (3 studies), and a transplantable methylcholantherene A
      induced sarcoma of CD2F1 mice (2 studies). We concurrently measured local cancer
      size and estrous cycle stage up to twice and at least once each day. There is a
      natural individual variability in the average length of normal estrus (3-1/2 to 7
      days) cycle in mice. We assessed the effect of the cycle stage and cycle duration
      on tumor size. RESULTS: We found identical estrous cycle stage coordination of
      cancer size, and identical effects of cycling frequency across all studies in
      each of these two tumors, both of which express both estrogen receptor alpha and
      progesterone receptor. Little or no change in cancer size occurs during proestrus
      (preovulatory phase) and estrus (periovulatory phase); tumor size increases
      several fold during diestrus (post-ovulatory phase); and the tumor shrinks
      partially as the next proestrus phase is approached. Across both mouse strains
      and tumor types, mice whose average cycle length is briefer (faster cyclers),
      have slower average tumor growth rate than those with longer cycles (slower
      cyclers) who have faster tumor growth rates. CONCLUSION: The virtually identical
      modulation of tumor size and cancer growth rate, in each of two very different
      transplantable cancers (one, classically sex-hormone-dependent, and the other,
      never previously recognized as hormone dependent) growing in two unrelated inbred
      mouse strains, indicates that the fertility cycle related host factors affect
      cancer size and growth rate. These experimental findings suggest that cancer cell
      proliferation of both breast and non-breast cancers in premenopausal women may be
      meaningfully coordinated by the menstrual cycle. If this proves to be the case,
      then any therapeutic strategy targeting proliferating cancer cells should be most
      effective against cancer of cycling women when given during the follicular phase
      of their menstrual cycles.

PMID- 15868437
TI  - Frequent down-regulation of HIVEP2 in human breast cancer.
AB  - The HIVEP2 gene, located on 6q23-q24, belongs to a family of genes that encodes
      large zinc fingers containing transcription factor proteins. Although this gene
      has been implicated in the regulation of immune responses and cellular
      proliferation, its functions are largely unknown. In the present study, we
      investigated HIVEP2 gene abnormalities in microdissected breast cancer tissue.
      For real-time quantitational RT-PCR analysis of paired normal and tumor tissues,
      mRNA levels were down-regulated to a maximum of 96%. The overall median
      expression level in breast cancer (33 cases) was significantly lower than that in
      normal breast tissue (normalized median value of 4.49 versus 17.68; p < 0.0001).
      Through full-length 5'-RACE (rapid amplification of cDNA ends) analysis, we
      identified multiple exons in the 5'-untranslated regions with multiple
      transcriptional start sites, four of which were located in a large CpG island. No
      tissue- or cancer-specific usage patterns for the transcription start sites were
      identified by multiplex RT-PCR analysis. Only faint methylation was detected in
      the 5' region of the island in normal cells and breast cancer tissue, indicating
      physiological, aging and no tumor-specific methylation. Mutation screening showed
      only germline polymorphisms. Thus, down-regulation of the HIVEP2 genes frequently
      occurs and may be one of the genetic events responsible for breast cancer, and
      their transcription may be regulated by complex mechanisms involving interactions
      with other factors and/or by other genetic/epigenetic mechanisms.

PMID- 15868438
TI  - An axilla scoring system to predict non-sentinel lymph node status in breast
      cancer patients with sentinel lymph node involvement.
AB  - BACKGROUND: Axillary lymph node dissection (ALND) is the current standard of care
      for breast cancer patients with sentinel lymph node (SN) involvement. However,
      the SN is the only involved axillary node in a significant proportion of these
      patients. Here we examined factors predictive of non-SN involvement in patients
      with a metastatic SN, in order to develop a scoring system for predicting non-SN
      involvement. MATERIALS AND METHODS: This study was based on a prospective
      database of 337 patients who underwent SN biopsy for breast cancer, of whom 81
      (24%) were SN-positive; we examined factors predictive of non SN involvement in
      the 71 of these 81 women who underwent complementary ALND. All clinical and
      histological criteria were recorded and analysed according to non-SN status, by
      using Chi-2 analysis, Student's t-test, and multivariate logistic regression.
      RESULTS: Univariate analysis showed a significant association between non-SN
      involvement and histological primary tumor size (p=0.0001), SN macrometastasis
      (p=0.01), the method used to detect SN metastasis (H&E versus
      immunohistochemistry) (p=0.03), the number of positive SNs (p=0.049), the
      proportion of involved SNs among all identified SNs (p=0.0001) and lymphovascular
      invasion (p=0.006). Histological primary tumor size (p=0.006), SN macrometastasis
      (p=0.02) and the proportion of involved SNs among all identified SNs (p=0.03)
      remained significantly associated with non-SN status in multivariate analysis.
      Based on the multivariate analysis, we developed an axilla scoring system (range
      0-7) to predict the likelihood of non-SN metastasis in breast cancer patients
      with SN involvement. CONCLUSION: In patients with invasive breast cancer and a
      positive SN, histological primary tumor size, the size of SN metastases, and the
      proportion of involved SNs among all identified SNs were independently predictive
      of non-SN involvement.

PMID- 15868439
TI  - Estimating the number of rate limiting genomic changes for human breast cancer.
AB  - We used multistage models that incorporate the age dependent dynamics of normal
      breast tissue, clonal expansion of intermediate cells and mutational events to
      fit data for the age-specific incidence of breast cancers in the surveillance,
      epidemiology, and end results (SEER) registry. Our results suggest that two or
      three rate limiting events occurring at rates characteristic of point mutation
      rates for normal mammalian cells set in motion a sequence of other genomic
      changes that lead with high probability to breast carcinoma.

PMID- 15868440
TI  - Lymph vessel density correlates with nodal status, VEGF-C expression, and
      prognosis in breast cancer.
AB  - Metastasis to the regional lymph nodes through the lymphatic vessels is a common
      step in the progression of cancer and an important prognostic factor in many
      types of cancer. Recent evidence suggests that VEGF-C promotes lymphangiogenesis,
      and that tumor lymphangiogenesis in turn promotes lymphatic metastasis. We have
      studied the role of LVD in breast cancer, and examined whether LVD is associated
      with lymph node metastasis, VEGF-C expression, or prognosis. In addition, we
      examined whether VEGF-C mRNA transcript levels were associated with lymph node
      metastasis and LVD. We began by investigating the lymphatics in primary human
      breast carcinoma with long-term follow-up (113 cases of invasive ductal and other
      breast cancers) by quantitative immunohistochemical staining for podoplanin. We
      then analyzed the relationship between LVD and lymph node status as well as VEGF
      C immunoreactivity and other established clinicopathological parameters. The
      relationship between LVD and prognosis was also studied. VEGF-C mRNA transcript
      levels were examined by quantitative real-time RT-PCR, in 55 invasive ductal
      breast carcinomas. This was followed by an analysis of the relationship between
      VEGF-C mRNA transcript levels and lymph node metastasis as well as LVD. Mean LVD
      of 'hot spots' was 10.2 +/- 7.4/each case. LVD was significantly correlated with
      lymph node metastasis (p < 0.0001), VEGF-C immunoreactivity (p = 0.0084), and
      podoplanin positive lymphatic invasion (p < 0.0001). Survival curves determined
      by the Kaplan-Meier method and univariate analysis demonstrated that high LVD was
      associated with both worse disease free survival (p = 0.0033) and overall
      survival (p = 0.0391). VEGF-C mRNA transcript levels were also correlated with
      lymph node metastasis (p = 0.0074) and LVD (p = 0.0409). Increased LVD was
      correlated with lymph node metastasis and VEGF-C expression. High LVD may be a
      significant unfavorable prognostic factor for long-term survival in breast
      cancer.

PMID- 15868441
TI  - Characterization of a human breast cancer cell line, MCF-7/RU58R-1, resistant to
      the pure antiestrogen RU 58,668.
AB  - Breast cancer is the most common cancer disease in women in the western world.
      Tamoxifen has been the standard first line endocrine therapy for patients with
      estrogen receptor (ER) positive tumors. Unfortunately, almost all patients with
      advanced disease develop tamoxifen resistance. This has lead to a search for new
      potent antiestrogens. One of the new compounds under development is the pure
      antiestrogen RU 58,668. To study the mechanisms behind acquired resistance to RU
      58,668, the RU 58,668-resistant cell line MCF-7/RU58(R)-1 (RU58(R)-1) was
      developed. The RU58(R)-1 cell line was responsive to tamoxifen, but cross
      resistant to ICI 182,780 and the estrogen-sensitivity was reduced compared to the
      parental MCF-7 cell line. The protein levels of ERalpha, IGF-I Receptor (IGF-IR)
      and Bcl-2 were severely reduced, when RU58(R)-1 cells were cultured with RU
      58,668 and the expression of progesterone receptor (PR) was lost. The ERalpha
      level increased upon withdrawal of RU 58,668 and the ERalpha protein was
      destabilized by RU 58,668 in both cell lines. Regulation of most of the
      investigated estrogen-sensitive mRNAs was found to be normal in the resistant
      cells. The protein levels of IGF-IR, Bcl-2 and the IGF Binding Protein 2 (IGFBP2)
      reverted towards MCF-7 levels upon RU 58,668 withdrawal, but the resistant
      phenotype was maintained. Thus, it appears as acquired resistance to RU 58,668 is
      not a result of loss of the ERalpha expression or function and we suggest that in
      the presence of RU 58,668, the RU58(R)-1 cell line probably uses other mitogenic
      pathways than the ERalpha pathway for growth and survival.

PMID- 15868442
TI  - Role of cyclin D1 in ErbB2-positive breast cancer and tamoxifen resistance.
AB  - Cyclin D1 plays an important role in the regulation of the G1 phase in the cell
      cycle. In mammary epithelial cells the expression of cyclin D1 is regulated
      through the oestrogen receptor and via ErbB2 signalling. Here we investigated the
      prognostic significance of cyclin D1 among 230 breast cancer patients randomised
      for tamoxifen, CMF chemotherapy and radiotherapy. The importance of combined
      cyclin D1 and ErbB2 overexpression was also analysed. Immunohistochemical
      analysis of the cyclin D1 expression resulted in 69 (29.8%) weakly positive, 107
      (46.5%) moderately positive and 54 (23.7%) strongly positive cases. The
      prognostic importance of ErbB2 was significantly greater for patients whose
      tumours overexpressed cyclin D1 than for other patients (p = 0.026). In the
      former group, ErbB2 overexpression was strongly associated with increased risk of
      recurrence (RR = 4.7; 95% CI, 2.1-10.4) and breast cancer death (RR = 5.4; 95%
      CI, 2.3-12.6). This result is in accordance with experimental studies
      demonstrating a link between cyclin D1 and ErbB2 in oncogenesis. Among oestrogen
      receptor positive patients, those with moderate cyclin D1 expression
      significantly did benefit from tamoxifen treatment (RR = 0.42; 95% CI, 0.21-0.82)
      whereas those with weak or strong expression did not. Therefore cyclin D1 might
      be a predictive marker for tamoxifen resistance.

PMID- 15868443
TI  - Economic outcomes of breast cancer survivorship: CALGB study 79804.
AB  - BACKGROUND: Over 80% of women diagnosed with breast cancer will be survivors. We
      sought to determine the economic consequences of surviving breast cancer.
      METHODS: Disease-free survivors who had received adjuvant chemotherapy for stage
      II breast cancer on CALGB study 8541 participated in a study of long-term
      outcomes. Survey responses were used to determine the types and frequency of
      medical resources used in follow-up, annual direct medical costs, and survivor
      perceptions of the personal economic impact of breast cancer. RESULTS: 245 of 314
      (78%) invited breast cancer survivors (median follow-up 12.2 years, range 9.3
      16.4) completed the surveys. Eighty-seven percent reported having cancer
      specialist follow-up in the past year. The following percentages of survivors
      reported having had, for breast cancer follow-up, at least once in the past year:
      breast examination 92%, mammogram 88%, bone scan 18%, chest radiograph 59%, tumor
      marker studies 37%. When follow-up care included a medical oncologist, resources
      were more likely to be used at least according to published follow-up guidelines,
      or over-used. Median annual cost of follow-up per survivor was US 630 dollars
      (range US 0-10,817 dollars) with higher costs associated with medical oncology
      follow-up, lower income, and younger age. Few women reported a negative impact of
      breast cancer on employment, but 16% reported being denied life insurance.
      CONCLUSIONS: Among long-term breast cancer survivors, patient self-report data
      suggest that over-use of medical resources for follow-up appears common. When
      follow-up care included a medical oncologist, resources were more likely to be
      used appropriately, or over-used. Costs of follow-up are higher with medical
      oncology follow-up, lower income and among younger survivors. The annual cost of
      follow-up varies widely and may be driven by over-use of follow-up tests.

PMID- 15868444
TI  - Immune dysfunction and micrometastases in women with breast cancer.
AB  - Cytokines produced by T lymphocytes are critical to the efficacy of a given
      immune response and dysregulation of immune responses may play a role in cancer
      progression. We assessed the intracellular cytokine profiles of T cells in the
      peripheral blood of women with breast cancer and explored the relationship of
      these responses with the presence of cancer in lymph nodes and bone marrow.
      Peripheral blood lymphocytes from 84 patients and 26 healthy volunteers were
      analyzed by 4-color flow cytometry for surface markers and for intracellular
      cytokines. Bone marrow samples from some of these patients were also collected
      and analyzed for the presence of epithelial cells (micrometastases) by flow
      cytometry. The percentages of both CD4(+) and CD8(+) cells producing type1 (IL-2,
      IFN-gamma or TNF-alpha) and type 2 (IL-4) were significantly lower in patients
      with breast cancer compared to healthy controls. These results indicate a general
      immune dysfunction in these patients as opposed to a shift in the balance of
      type1 and type2 cells. These dysregulated T cell responses did not correlate with
      age, stage of disease, or nodal status. However, we did observe a correlation
      between number of micrometastases in the bone marrow and T cell responsiveness.

PMID- 15868445
TI  - Metaplastic breast carcinoma: clinical-pathologic characteristics and HER2/neu
      expression.
AB  - BACKGROUND: Metaplastic breast carcinomas (MBC) are rare primary breast
      malignancies characterized by the co-existence of carcinoma with non-epithelial
      cellular elements. They can be classified as monophasic spindle cell
      (sarcomatoid) carcinoma, biphasic carcinosarcoma, adenocarcinoma with divergent
      stromal differentiation (osseous, chondroid and rarely rhabdoid) as well as
      adenosquamous and pure squamous cell carcinomas. There is a paucity of
      information on clinically relevant pathologic features and clinical outcomes for
      these rare tumors. The aim of this study was to review the pathologic features
      and clinical outcomes of all cases of MBC seen at a single institution between
      1971 and 2000. METHODS: A computerized search of the Queen Elizabeth II Health
      Sciences Center (QEII HSC) surgical pathology files was performed for the years
      1971-2000. Tumor blocks from identified cases were reviewed and
      immunohistochemistry was performed for estrogen and progesterone receptors
      (ER/PR), HER2/neu protein overexpression and cytokeratin profile. Clinical
      outcome information was obtained from hospital files and telephone contact with
      treating physicians. RESULTS: Twenty-six (26) cases were retrieved with only one
      case identified before 1990. All tumors were high grade with a median tumor size
      of 3.7 cm (range 1.4-9.5 cm). Thirteen cases had lymph node dissections available
      for evaluation, with 4 demonstrating nodal metastases. Five of 26 cases were ER
      positive within the adenocarcinomatous component, only two of which also
      expressed PR. Associated ductal carcinoma in situ (DCIS) was present in 11 cases.
      HER2/neu over-expression was seen in only one (1/26) adenosquamous carcinoma (3 +
      membranous staining of the malignant glandular component). At 23 months median
      follow-up, disease free survival (DFS) for the entire group was 53%. CONCLUSIONS:
      Although a rare breast cancer subtype, MBC is of considerable interest due to its
      pathological heterogeneity and differences in clinical behavior compared to
      typical breast carcinomas. Increasing pathologic recognition of MBC as a discrete
      entity is suggested by the number of MBC diagnoses in the last decade compared to
      previous years. The poor DFS associated with MBC suggests that further research
      exploring mechanisms of carcinogenesis and identifying clinically relevant
      prognostic factors is needed to direct optimum clinical care. Importantly, MBC
      variants appear to rarely overexpress the HER2/neu oncoprotein.

PMID- 15868446
TI  - BRCA1 promoter methylation in sporadic breast tumors: relationship to gene
      expression profiles.
AB  - BRCA1 is a tumor suppressor gene that functions in DNA repair. Basal-like tumors
      are a distinctive subtype of breast cancer defined by gene expression profiles.
      Hereditary BRCA1 breast tumors and basal-like sporadic tumors have a similar
      phenotype and gene expression signature, suggesting involvement of BRCA1 in the
      pathogenesis of sporadic basal-like cancer. This study evaluates the role of
      BRCA1 in sporadic breast tumorigenesis. BRCA1 protein expression and promoter
      methylation are compared to tumor histopathology and gene expression profiles. We
      find BRCA1 protein expression correlates with tumor mitotic rate, consistent with
      normal cell-cycle regulation of the BRCA1 gene. Methylation is found in 21% of
      tumors and is associated with lower BRCA1 protein, but not with specific
      pathologic features. Basal-like tumors, defined by hierarchical clustering of
      gene expression, have infrequent BRCA1 methylation and high levels of BRCA1
      protein expression consistent with their high mitotic rate. Tumors with BRCA1
      promoter methylation are present in all expression clusters; however, a subgroup
      of ER-positive high-grade tumors has a significantly greater number of BRCA1
      methylated tumors. Absence of BRCA1 promoter methylation and high levels of BRCA1
      expression in basal-like sporadic tumors suggest alternate explanations for the
      phenotypic similarities of these tumors to hereditary BRCA1 tumors.

PMID- 15868447
TI  - Differential sensitivities of trastuzumab (Herceptin)-resistant human breast
      cancer cells to phosphoinositide-3 kinase (PI-3K) and epidermal growth factor
      receptor (EGFR) kinase inhibitors.
AB  - Her2 (erbB2/neu) is overexpressed in 25-30% of human breast cancers. Herceptin is
      a recombinant humanized Her2 antibody used to treat breast cancer patients with
      Her2 overexpression. Over a 5-month selection process, we isolated clones of
      BT474 (BT) human breast carcinoma cells (BT/Her(R)) that were resistant to
      Herceptin in vitro. In BT/Her(R) subclones, cell-surface, phosphorylated and
      total cellular Her2 protein remained high in the continuous presence of
      Herceptin. Likewise, the levels of cell-surface, phosphorylated, and total
      cellular Her3 and EGFR were either unchanged or only slightly elevated in
      BT/Her(R) subclones relative to BT cells. One BT/Her(R) subclone had
      substantially upregulated cell-surface EGFR, but this did not correlate with a
      higher relative resistance to Herceptin. In looking at the downstream PI-3K/Akt
      signaling pathway, phosphorylated and total Akt levels and Akt kinase activities
      were all sustained in BT/Her(R) subclones in the presence of Herceptin, but
      significantly downregulated in BT cells exposed to Herceptin. Whereas BT cells
      lost sensitivity to the PI-3K inhibitor LY294002 in the presence of Herceptin,
      BT/Her(R) subclones were equally sensitive to this agent in the presence and
      absence of Herceptin. This suggests that BT/Her(R) subclones acquired a Herceptin
      resistant mechanism of PI-3K signaling. BT/Her(R) subclones were also sensitive
      to the EGFR kinase inhibitor AG1478 in the presence of Herceptin, to the same
      extent as BT cells. The BT/Her(R) subclones provide new insights into mechanisms
      of Herceptin resistance and suggest new treatment strategies in combination with
      other inhibitors targeted to signal transduction pathways.

PMID- 15868448
TI  - A breast cancer patient from Italy with germline mutations in both the BRCA1 and
      BRCA2 genes.
AB  - We report the first case in Italy of a non-Ashkenazi double heterozygote for
      BRCA1 and BRCA2 genes. This finding is predictably rare, with a maximum frequency
      of 1/250,000. The proband and her mother were diagnosed with early-onset breast
      cancer. No other relatives with breast and/or ovarian cancer were observed. The
      implications of this case in regard to genetic testing and counseling are
      substantial.

PMID- 15868449
TI  - Interaction between environmental tobacco smoke and arsenic methylation ability
      on the risk of bladder cancer.
AB  - OBJECTIVE: Arsenic exposure and environmental tobacco smoke (ETS) have been
      suspected to be associated with bladder cancer risk. We hypothesize that
      interaction between ETS and the ability to methylate arsenic, a detoxification
      pathway, modifies the risk of bladder cancer. METHODS: From January 1996 to
      December 1999, we identified 41 newly diagnosed bladder cancer patients and 202
      fracture and cataract patients at the National Cheng-Kung University (NCKU)
      Medical Center. The levels of urinary arsenic species [As(III), As(V), MMA(V),
      and DMA(V)] were determined in all subjects. RESULTS: We found significant
      interaction between ETS and secondary methylation index (SMI) on the risk of
      bladder cancer (p=0.02). Among non-smokers with a high primary methylation index
      (PMI), the risk of bladder cancer was lower in subjects exposed to ETS (OR, 0.37;
      95% CI, 0.14-0.96) than in subjects without exposure to ETS. Among non-smokers
      without ETS, the risk of bladder cancer was 4.7 times higher in subjects with a
      low SMI (95% CI, 1.30-16.81) than in subjects with a high SMI. CONCLUSIONS:
      Ability to methylate arsenic plays an important role in reducing the risk of
      bladder cancer attributable to the continuation of arsenic exposure from drinking
      water and from ETS exposure.

PMID- 15868450
TI  - The epidemiology of vitamin D and cancer incidence and mortality: a review
      (United States).
AB  - In vitro and animal studies indicate that vitamin D may have anti-cancer
      benefits, including against progression and metastasis, against a wide spectrum
      of cancers. Supporting an anti-cancer effect of vitamin D is the ability of many
      cells to convert 25(OH)D, the primary circulating form of vitamin D, into
      1,25(OH)2D, the most active form of this vitamin. No epidemiologic studies have
      directly measured vitamin D concentrations or intakes on risk of total cancer
      incidence or mortality. However, higher rates of total cancer mortality in
      regions with less UV-B radiation, and among African-Americans and overweight and
      obese people, each associated with lower circulating vitamin D, are compatible
      with a benefit of vitamin D on mortality. In addition, poorer survival from
      cancer in individuals diagnosed in the months when vitamin D levels are lowest
      suggests a benefit of vitamin D against late stages of carcinogenesis. The only
      individual cancer sites that have been examined directly in relation to vitamin D
      status are colorectal, prostate and breast cancers. For breast cancer, some data
      are promising for a benefit from vitamin D but are far too sparse to support a
      conclusion. The evidence that higher 25(OH)D levels through increased sunlight
      exposure or dietary or supplement intake inhibit colorectal carcinogenesis is
      substantial. The biologic evidence for an anti-cancer role of 25(OH)D is also
      strong for prostate cancer, but the epidemiologic data have not been supportive.
      Although not entirely consistent, some studies suggest that higher circulating
      1,25(OH)2D may be more important than 25(OH)D for protection against aggressive,
      poorly-differentiated prostate cancer. A possible explanation for these divergent
      results is that unlike colorectal tumors, prostate cancers lose the ability to
      hydroxylate 25(OH)D to 1,25(OH)2D, and thus may rely on the circulation as the
      main source of 1,25(OH)2D. The suppression of circulating 1,25(OH)2D levels by
      calcium intake could explain why higher calcium and milk intakes appear to
      increase risk of advanced prostate cancer. Given the potential benefits from
      vitamin D, further research should be a priority.

PMID- 15868451
TI  - Testicular cancer, occupation and exposure to chemical agents among Finnish men
      in 1971-1995.
AB  - OBJECTIVE: To find associations between testicular cancer, occupation and
      chemical exposure. METHODS: A cohort of all economically active Finnish men born
      between 1906 and 1945 was followed-up for 19.7 million person-years during 1971
      1995. Incident cases of testicular cancer (n=387) were identified in a record
      linkage with the Finnish Cancer Registry. The Census occupations in 1970 were
      converted to chemical exposures with a job-exposure matrix (FINJEM). Cumulative
      exposure (CE) was calculated as the product of prevalence, level, and duration of
      the exposure. Standardised incidence ratio (SIR) was calculated for each of the
      393 occupations, and for CE categories of the 43 chemical agents, using average
      male population as reference. Relative risks (RR) comparing various CE-categories
      with unexposed ones were defined for selected agents by Poisson regression
      analysis. RESULTS: Elevated SIRs were observed among railway traffic supervisors
      (5.8, 95% CI 1.6-14.7), programmers (4.3, 1.4-9.9), university teachers (4.1, 1.3
      9.5) and electrical engineers (3.9, 1.1-10.1). A significant exposure-response
      trend (mainly contributed by seminoma) was observed for pesticides, textile dust,
      aliphatic and alicyclic hydrocarbons, and some other organic solvents.
      CONCLUSIONS: Risk of testicular cancer increased only in four occupations.
      Pesticides, textile dust, and some organic solvents may be related to an excess
      risk of seminoma.

PMID- 15868452
TI  - Cancer-specific beliefs and survival: a population-based study of African
      American and White breast cancer patients.
AB  - OBJECTIVE: Beliefs about cancer and its treatment have been shown to influence
      cancer stage at diagnosis and, thus, prognosis. The association between these
      beliefs and survival is understudied, especially among racially/ethnically
      diverse populations. We investigated the relationship between cancer-specific
      beliefs and survival in a cohort of African-American and White women with newly
      diagnosed breast cancer followed for up to 15 years. METHODS: We examined beliefs
      about cancer detection, treatment, and curability in a population-based cohort of
      145 African-American and 177 White women diagnosed with breast cancer in
      Connecticut, US, between 1987 and 1989. Cox proportional-hazards models were
      adjusted for stage at diagnosis, other biomedical variables, socio-demographic
      and lifestyle factors. RESULTS: In multivariate models, perceived cancer
      incurability was associated with a higher risk of death from any cause (hazards
      ratio (HR)=1.67, 95 confidence interval (CI)=1.11, 2.51). Further control for
      tumor characteristics, genetic alterations, access to care, and additional
      psychosocial factors did not alter these findings. Other cancer-specific beliefs
      examined here were not related to survival. CONCLUSIONS: Perceived cancer
      incurability is independently associated with survival among breast cancer
      patients in fully adjusted models. The identification of the underlying
      mechanisms of this association has potential for translation into intervention
      strategies for cancer patients.

PMID- 15868453
TI  - What do cancer survivors believe causes cancer? (United States).
AB  - OBJECTIVE: To describe cancer survivors' beliefs about the causes of prostate,
      colorectal or breast cancers. METHODS: A survey of beliefs about cancer causation
      was completed by 670 cancer survivors (416 with breast cancer, 165 with prostate
      cancer and 89 with colorectal cancer) enrolled in a population-based study in
      Colorado. Categorical analysis was used to describe associations between
      participant's beliefs about the cause of their cancer type, both in themselves
      and in others, and personal characteristics, including gender, age, and familial
      cancer risk. RESULTS: Cancer survivors most frequently reported genetic factors,
      smoking, environmental factors (e.g., pollutants or occupation), and psychosocial
      factors (e.g., stress) as causing their type of cancer. Respondents
      underestimated the importance of behavioral factors that are known to be
      associated with increased cancer risk, such as obesity and physical inactivity,
      while overestimating the importance of stress and environmental pollution.
      CONCLUSIONS: Cancer survivors' beliefs about what causes cancer are substantially
      different than those of experts. Because those affected by cancer should be well
      informed about the causes of cancer, educational efforts are needed, especially
      regarding the importance of factors that can be modified to reduce cancer risk.

PMID- 15868454
TI  - Towards a dietary prevention of hereditary breast cancer.
AB  - Inheritance of a deleterious mutation in BRCA1 or BRCA2 confers a high lifetime
      risk of developing breast cancer. Variation in penetrance between individuals
      suggests that factors other than the gene mutation itself may influence the risk
      of cancer in susceptible women. Several risk factors have been identified which
      implicate estrogen-induced growth stimulation as a probable contributor to breast
      cancer pre-disposition. The protein products of both of these genes appear to
      help preserve genomic integrity via their participation in the DNA damage
      response and repair pathways. To date, the evidence for a cancer-protective role
      of dietary nutrients, for the most part those with antioxidant properties, has
      been based on women without any known genetic pre-disposition and it is important
      to identify and evaluate dietary factors which may modify the risk of cancer in
      BRCA carriers. Here we propose that diet modification may modulate the risk of
      hereditary breast cancer by decreasing DNA damage (possibly linked to estrogen
      exposure) or by enhancing DNA repair. The prevention of hereditary breast cancer
      through diet is an attractive complement to current management strategies and
      deserves exploration.

PMID- 15868455
TI  - Regional variations in breast cancer incidence among California women, 1988-1997.
AB  - BACKGROUND: Internationally, California has some of the highest breast cancer
      rates; these rates also show substantial regional variations within the state.
      This study describes geographic breast cancer incidence patterns within
      California and evaluates the degree to which socioeconomic status (SES) and
      urbanization explain the regional variability. METHODS: Invasive breast cancer
      cases in women > or =20 year of age were identified from the California Cancer
      Registry, for 1988-1997, then assigned to one of three regions (San Francisco Bay
      Area, Southern Coastal Area and the rest of California), based on residence at
      diagnosis. Neighborhood SES and urbanization were derived from U.S. Census data.
      Rate ratios (RR) and 95% confidence intervals (CI) were computed using Poisson
      regression. Analyses were conducted for all invasive breast cancer cases
      (n=176,302) and by selected histologic subtypes: ductal (n=121,619); lobular
      (n=13,410); mixed ductal and lobular (n=9744). RESULTS: Compared to block groups
      with the lowest quartile of SES, rates were highest in block groups with high
      SES. Rates also were higher in suburban and city areas than in small town/rural
      areas. Compared to the rest of California, age- and race-adjusted rates for all
      breast cancer were approximately 20% higher in the San Francisco Bay Area and 10%
      higher in the Southern Coastal Area. After adjusting for SES and urbanization the
      rate ratios were reduced to near unity (RR=1.06, 95% CI: 1.03-1.09 for San
      Francisco Bay Area; RR=1.02, 95% CI: 0.99-1.04 for Southern Coastal Area). Rates
      ratios for ductal carcinomas mirrored those for all cases. For lobular cases,
      rate ratios remained elevated after adjustment for age, race/ethnicity,
      neighborhood SES and urbanization (RR=1.18, 95% CI: 1.11-1.27 for San Francisco
      Bay Area; RR=1.10, 95% CI: 1.04-1.17 for Southern Coastal Area). For the subset
      of cases with mixed ductal and lobular histologies, the rate ratio for the San
      Francisco Bay Area was no longer elevated after adjusting for age,
      race/ethnicity, SES and urbanization (RR=0.92, 95% CI: 0.84-1.01); the adjusted
      rate ratio for the Southern Coastal Area, however, remained elevated (RR=1.22,
      95% CI: 1.12-1.32). CONCLUSIONS: Regional differences in neighborhood SES and
      urbanization appear to largely explain regional rate differences in California
      for all breast cancers and ductal carcinomas but do not fully explain geographic
      patterns of breast cancer with a lobular component.

PMID- 15868456
TI  - A national framework for cancer surveillance in the United States.
AB  - Enhancements to cancer surveillance systems are needed for meeting increased
      demands for data and for developing effective program planning, evaluation, and
      research on cancer prevention and control. Representatives from the American
      Cancer Society, Centers for Disease Control and Prevention, National Cancer
      Institute, National Cancer Registrars Association, and North American Association
      of Central Cancer Registries have worked together on the National Coordinating
      Council for Cancer Surveillance to develop a national framework for cancer
      surveillance in the United States. The framework addresses a continuum of disease
      progression from a healthy state to the end of life and includes primary
      prevention (factors that increase or decrease cancer occurrence in healthy
      populations), secondary prevention (screening and diagnosis), and tertiary
      prevention (factors that affect treatment, survival, quality of life, and
      palliative care). The framework also addresses cross-cutting information needs,
      including better data to monitor disparities by measures of socioeconomic status,
      to assess economic costs and benefits of specific interventions for individuals
      and for society, and to study the relationship between disease and individual
      biologic factors, social policies, and the environment. Implementation of the
      framework will require long-term, extensive coordination and cooperation among
      these major cancer surveillance organizations.

PMID- 15868457
TI  - Colorectal cancer screening in average risk individuals.
AB  - Colorectal cancer is the third leading type of cancer, and the second leading
      cause of cancer-related death in the United States. Prevention of colorectal
      cancer should be achievable by screening programs that detect adenomas in
      asymptomatic patients and lead to their removal. In this manuscript, we review
      the major screening modalities, the advantages and disadvantages of each
      approach, the data supporting their use, and various issues affecting the
      implementation of each test. Screening guidelines will be reviewed, and future
      techniques for colorectal cancer screening examined.

PMID- 15868458
TI  - Lung cancer risk in the vinyl chloride industry.

PMID- 15868461
TI  - Gamma-hydroxybutyric aciduria: a biochemist's education from a heritable disorder
      of GABA metabolism.
AB  - In keeping with the theme of the 41st Annual Symposium (Metabolic
      Encephalopathies), the current report provides an overview of a quarter century
      of research investigating a rare inborn error of GABA metabolism, succinic
      semialdehyde dehydrogenase (SSADH) deficiency (also referred to as gamma
      hydroxybutyric aciduria). The clinical phenotype, treatment challenges,
      pathomechanistic concepts, as well as metabolic, enzymatic and molecular
      characteristics, of the disorder are summarized. In addition, important features
      of a recently developed murine model are presented, with discussion of how this
      model has broadened thinking about, and treatment approaches to, the clinical
      disease. In addition, a brief scientific history of the author is provided, and
      an account of how serendipitous circumstances brought him together with other
      colleagues to begin delineating the aetiological mechanisms in SSADH deficiency.
      The evolution of research on SSADH deficiency re-establishes the classical
      approach beginning at clinical characterization, evolving to enzyme and
      metabolite identification as well as molecular characterization, and eventually
      to model development and preclinical treatment approaches. This scientific
      evolution admirably supports the life and ideals of Dr George Komrower, in whose
      honour this lecture is named.

PMID- 15868462
TI  - Dominantly inherited hyperinsulinaemic hypoglycaemia.
AB  - Congenital hyperinsulinism (HI), the most important cause of hypoglycaemia in
      early infancy, is a heterogeneous disease with two types of histological lesions,
      focal and diffuse, with major consequences in terms of surgical approaches. In
      contrast to focal islet-cell hyperplasia, always sporadic to our knowledge,
      diffuse hyperinsulinism is a heterogeneous disorder involving several genes,
      various mechanisms of pathogenic mutations and different transmissions: (i)
      channelopathy involving the genes encoding the sulphonylurea receptor (SUR1) or
      the inward-rectifying potassium channel (Kir6.2) in recessively inherited HI or
      more rarely dominantly inherited HI; (ii) metabolic disorders implicating the
      short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) enzyme inrecessively
      inherited HI, the glucokinase gene (GK), the glutamate dehydrogenase gene (GLUD1)
      when hyperammonemia is associated, dominant exercise-induced HI with still
      unknown mechanism, and more recently the human insulin receptor gene in
      dominantly inherited hyperinsulinism. Thus, dominant HI disorders always
      correspond to diffuse HI, where most hypoglycaemia occur in infancy, and are
      sensitive to medical treatment. Channel causes could be due to dominant negative
      mutation with one abnormality in channels composed of four Kir6.2 subunits and
      four SUR1 subunits, leading to a complete destruction of the channel structure or
      function, or due to haploinsufficiency with only one functional allele, leading
      to 50% of functional protein, which is not sufficient to obtain enough opened
      channels to maintain the membrane depolarized. Metabolic causes are due to a gain
      of function of enzyme activity (deregulated enzymes), except for physical
      exercise-induced hyperinsulinaemic hypoglycaemia, of still-unknown cause.
      Congenital hyperinsulinism (HI) is the most important cause of hypoglycaemia in
      early infancy (Aynsley-Green et al 2000; Cornblath et al 1990; Pagliara et al
      1973; Thomas et al 1977). The inappropriate oversecretion of insulin is
      responsible for profound hypoglycaemia that requires aggressive treatment to
      prevent severe and irreversible brain damage (Volpe 1995). HI is a heterogeneous
      disease associated with several genes, various mechanisms of pathogenic mutations
      and different transmissions (Dunne et al 2004).

PMID- 15868463
TI  - Molecular mechanisms of dominant expression in porphyria.
AB  - Partial deficiency of enzymes in the haem synthetic pathway gives rise to a group
      of seven inherited metabolic disorders, the porphyrias. Each deficiency is
      associated with a characteristic increase in haem precursors that correlates with
      the symptoms associated with individual porphyrias and allows accurate diagnosis.
      Two types of clinical presentation occur separately or in combination; acute life
      threatening neurovisceral attacks and/or cutaneous symptoms. Five of the
      porphyrias are low-penetrance autosomal dominant conditions in which clinical
      expression results from additional factors that act by increasing demand for haem
      or by causing an additional decrease in enzyme activity or by a combination of
      these effects. These include both genetic and environmental factors. In familial
      porphyria cutanea tarda (PCTF), environmental factors that include alcohol,
      exogenous oestrogens and hepatotropic viruses result in inhibition of hepatic
      enzyme activity via a mechanism that involves excess iron accumulation. In
      erythropoietic protoporphyria (EPP), co-inheritance of a functional polymorphism
      in trans to a null ferrochelatase allele accounts for most clinically overt
      cases. In the autosomal dominant acute hepatic porphyrias (acute intermittent
      porphyria, variegate porphyria, hereditary coproporphyria), acute neurovisceral
      attacks occur in a minority of those who inherit one of these disorders. Although
      various exogenous (e.g. drugs, alcohol) and endogenous factors (e.g. hormones)
      have been identified as provoking acute attacks, these do not provide a full
      explanation for the low penetrance of these disorders. It seems probable that
      genetic background influences susceptibility to acute attacks, but the genes that
      are involved have not yet been identified.

PMID- 15868464
TI  - Dominance in mitochondrial disorders.
AB  - Dominant traits are rare in mitochondrial disorders but include important
      nosological entities such as alterations of organellar biogenesis and
      abnormalities in the structural integrity of the mitochondrial genome, determined
      by mutations in genes involved in its maintenance and propagation. Both haplo
      insufficiency and 'gain-of-function' mechanisms underlie the pathogenesis of
      these disorders. Impairment in energy supply, abnormal mitochondrial trafficking,
      increased toxic damage by oxygen radicals, and mitochondrially driven apoptosis
      have been documented in different dominant syndromes. In addition, maternally
      inherited mutations of mitochondrial DNA can sometimes simulate dominant traits,
      mainly because of reduced penetrance and complex interaction with genetic and
      environmental factors.

PMID- 15868465
TI  - Molecular mechanism of dominant expression in 3-methylcrotonyl-CoA carboxylase
      deficiency.
AB  - Most enzyme deficiencies in humans are inherited as autosomal recessive traits.
      The term dominant negative is applied to mutant alleles in which a mutant protein
      interferes in one way or another with the function of the normal protein being
      produced from the wild-type allele in a heterozygote. Such a dominant negative
      effect usually involves homomeric or heteromeric proteins. 3-Methylcrotonyl-CoA
      carboxylase (MCC) is a heteromeric mitochondrial enzyme comprised of biotin
      containing MCCalpha subunits and smaller MCCbeta subunits, encoded by the genes
      MCCA and MCCB, respectively. Mutations in these genes cause isolated MCC
      deficiency, an autosomal recessive disorder with a variable phenotype ranging
      from severe neonatal to asymptomatic adult forms. Patients with MCC deficiency
      have a characteristic organic aciduria with greatly increased excretion of 3
      hydroxyisovaleric acid (3-HIVA) and 3-methylcrotonyl-glycine (3-MCG). Here, two
      patients with elevated excretion of 3-MCG and 3-HIVA and partial deficiency of
      MCC are discussed, one of them with severe neurological symptoms. Both showed
      evidence of biotin responsiveness and were heterozygous for the missense mutation
      MCCA-R385S. Evidence is presented that MCCA-R385S is a dominant negative allele
      leading to biochemical abnormalities and clinical symptoms in heterozygous
      individuals and that it is responsive to pharmacological doses of biotin in vivo.

PMID- 15868466
TI  - Magnetic resonance techniques in the assessment of myelin and myelination.
AB  - Leukodystrophy is a common central nervous system manifestation of inborn errors
      of metabolism. Until magnetic resonance imaging (MRI) emerged as a clinical tool,
      the diagnosis of leukodystrophy was difficult and imprecise; MRI has allowed new
      understandings and classifications of leukodystrophies that have greatly enhanced
      both our diagnostic ability and our understanding of these complex disorders.
      However, optimal use of MRI in this setting requires a fundamental understanding
      of myelin structure, myelin development, and the changes seen on MRI with
      myelination and demyelination. The purpose of this review is to provide the
      reader with the necessary tools for the use of MRI to diagnose and follow
      patients with leukodystrophies.

PMID- 15868468
TI  - Oligodendrocytes and stem cell transplantation: their potential in the treatment
      of leukoencephalopathies.
AB  - Cell transplantation is being extensively explored as a means of treating many
      human degenerative diseases. The leukodystrophies are examples of neurological
      disorders where new therapeutic strategies, either cellular or molecular, will be
      required to repair the central nervous system (CNS) of affected patients. Much
      hope is being pinned on the use of human embryonic stem (ES) cells as the
      exogenous source of neurons and glia to replace dysfunctional or dying cells in
      the CNS. In the case of leukoencephalopathies, the goal is to generate
      oligodendrocytes or other myelinating cells such as Schwann cells from ES cells,
      to myelinate or remyelinate CNS axons on transplantation. Experimental data
      suggests that mouse ES cells have this capacity, but at present differentiation
      of oligodendrocytes in sufficient numbers from human ES cells is not possible. It
      may in fact be more feasible to isolate oligodendrocytes from human neural stem
      cells derived from the fetal brain, but the source of these is in short supply
      and, like that of ES cells, is ethically controversial. None the less, it appears
      certain that either of these two sources will eventually give rise to sufficient
      numbers of neural stem cells or oligodendrocyte progenitors that have greater
      capacity for repair than such cells derived from the adult brain. Once the
      primary technical issues concerning human ES cell differentiation have been
      overcome, the most likely first clinical target will be Pelizaeus-Merzbacher
      disease. However, widespread dissemination of cells throughout the CNS may be
      required for functional improvement; hence diseases such as adrenoleukodystrophy
      may also be considered as therapeutic targets.

PMID- 15868467
TI  - Disorders of intermediary metabolism: toxic leukoencephalopathies.
AB  - Myelination starts in the latter half of gestation. It is initiated by
      oligodendrocyte progenitor cells. Three sequential steps can be distinguished:
      (1) initial ensheathment of axons by premyelin sheaths generated by
      oligodendrocyte progenitor cells; (2) initial insertion of myelin basic protein
      (MBP) into transitional sheaths; and (3) generation of mature MBP-rich myelin.
      Different inborn errors of metabolism can interfere with different stages of
      these physiological processes, causing white-matter diseases, i.e. toxic
      leukoencephalopathies. Some inborn errors of metabolism disturb the formation of
      myelin by being toxic to oligodendrocytes or by interference with the
      biosynthesis of cholesterol and lipids, e.g. globoid cell leukodystrophy and
      phenylketonuria. Remethylation defects, e.g. methylenetetrahydrofolate reductase
      deficiency, cobalamin C, D, E, F and G defects, interfere with the expression,
      processing and insertion of MBP. The concept of excitotoxicity, which has been
      developed in neurons, has recently been modified and has been extended to the
      oligodendroglial lineage. Mitochondriopathies and cerebral organic acid disorders
      may cause secondary excitotoxicity resulting in toxic encephalopathies, which may
      affect both neurons and oligodendrocytes. This review aims to present relevant
      diseases, summarizing recent knowledge on mechanisms and formulating testable
      hypotheses of pathophysiology leading to new and improved treatment strategies.

PMID- 15868469
TI  - Peroxisome biogenesis disorders: the role of peroxisomes and metabolic
      dysfunction in developing brain.
AB  - Peroxisome biogenesis disorders, of which Zellweger syndrome is the most severe,
      result in severe neurological dysfunction associated with abnormal CNS neuronal
      migrations due to the lack of functional peroxisomes. The PEX2-/- mouse model for
      Zellweger syndrome has enabled us to evaluate the role of peroxisomes in the
      development and functioning of the nervous system. These studies have shown that,
      in addition to disturbances in neuronal migration in developing cerebral cortex
      and cerebellum, defects in neuronal differentiation, proliferation and survival
      may also contribute to the CNS malformations. However, owing to the multiorgan
      dysfunction in peroxisomal disorders, it has been difficult to clearly define an
      intrinsic role for the peroxisome in brain cells. The use of several in vitro
      cell culture assays to evaluate the migration and differentiation of cerebellar
      neurons demonstrates a persistence of defects in peroxisome-deficient neurons.
      The absence of potential systemically derived, extrinsic factors in these in
      vitro systems indicates that CNS intrinsic defects contribute to the pathogenesis
      of disease in these disorders. However, bile acid treatment also increases the
      survival and growth of PEX2-/- mice and improves some aspects of cerebellar
      development, indicating that extrinsic factors also affect the developing
      peroxisome-deficient brain. Therefore, the final phenotype of nervous system
      dysfunction in peroxisomal disorders will reflect a combination of both CNS
      intrinsic and extrinsic factors.

PMID- 15868470
TI  - Congenital brain anomalies in distal cholesterol biosynthesis defects.
AB  - Cholesterol is known to be a significant constituent of the central nervous
      system. It also plays an important role in developmental pathways to form the
      human brain, such as the Sonic Hedgehog pathway. Disturbances in the formation of
      cholesterol may therefore be expected to cause brain malformations and brain
      dysfunctions. Here a short review of the consequences of defects of the distal
      cholesterol pathways to brain formation and functioning is provided.

PMID- 15868471
TI  - Congenital brain malformations in mitochondrial disease.
AB  - The majority of patients with mitochondrial disease have some degree of
      neuropathology and this is usually degenerative in nature. However, in a subset
      of mitochondrial diseases there are additional specific and characteristic
      congenital malformations in the brain. These developmental abnormalities are not
      unique to mitochondrial diseases and their association with only some conditions
      suggests that they are not simply due to energy deprivation or accumulation of
      metabolites such as lactic acid. Pathogenic mechanisms are at present unknown,
      but interference with neurotransmitter homeostasis, in addition to altered energy
      metabolism, may be important. The postnatal evolution of the neuropathology in
      these conditions and the type and pattern of the malformations suggest secondary
      degeneration of specific brain structures during fetal life rather than primary
      interference with developmental pathways.

PMID- 15868472
TI  - Acute metabolic encephalopathy: an introduction.
AB  - Acute encephalopathy is a common and potentially serious problem in patients with
      inborn errors of metabolism. There are many causes and the diagnosis and
      treatment are both urgent. However, the pathogenesis is rarely well understood
      and, as a result, treatment of the complications is often problematic.

PMID- 15868473
TI  - Urea cycle defects: management and outcome.
AB  - This paper reviews the clinical presentation of 217 patients with urea cycle
      defects, including 121 patients with neonatal-onset forms and 96 patients with
      late-onset forms. Long-term outcome of these patients is also reported with the
      severity of the neonatal forms of these disorders, mostly for ornithine
      carbamoyltransferase-deficient males. Patients with late-onset forms may present
      at any age and carry a 28% mortality rate and a subsequent risk of subsequent
      disabilities.

PMID- 15868474
TI  - Methylmalonic and propionic acidaemias: management and outcome.
AB  - Organic acidurias comprise many various disorders. Methylmalonic aciduria (MMA)
      and propionic aciduria (PA) are the most frequent diseases and the two organic
      acidurias for which we have better knowledge of the long-term outcome. Comparing
      the outcome of patients born before and after 1990, it appears that better
      neonatal and long-term management have improved the survival rate. Less than 20%
      of the patients died in either the neonatal period or before the age of 10 years.
      However, most surviving patients showed poor nutritional status with growth
      retardation and about 40% present some kind of visceral or neurological
      impairment. The developmental outcome may have improved in MMA patients, with IQ
      higher than 75 in about 40% patients aged more than 4 years. Conversely, poor
      intellectual development is the rule in PA patterns, with 60% having an IQ less
      than 75 and requiring special education. Successful liver and/or renal
      transplantations, in a few patients, have resulted in better quality of life but
      have not necessarily prevented neurological and various visceral complications.
      These results emphasize the need for permanent metabolic follow-up whatever the
      therapeutic strategy.

PMID- 15868475
TI  - Movement disorders: classifications.
AB  - Movement disorders (ataxia, dystonic disorders, gait disorders, Huntington
      disease, myoclonus, parkinsonism, spasticity, tardive dyskinesia, tics and
      tremor) are clinically, pathologically and genetically heterogeneous and are
      characterized by impairment of the planning, control or execution of movement.
      Current classifications of these disorders have inherent shortcomings due to the
      complex nature of movement disorders and the lack of diagnostic tests for the
      majority. Undiscriminating terminology, as well as the clinical, pathological and
      genetic heterogeneity, further complicate the development of comprehensive
      categorizations. Modern classification schemes tend to focus on clinical,
      pathological or genetic/molecular criteria, but more recent attempts have been
      made to integrate across these levels. From a historical perspective, two 'golden
      ages' have shaped the current and evolving classification schemes: (1) the
      definition of clinical pathological entities in the early twentieth century and
      (2) the application of molecular neurogenetics in the past 10-15 years. However,
      the classification of movement disorders on clinical grounds (according to age at
      onset, distribution of symptoms, disease course, provoking factors and
      therapeutic response) remains one of the most useful modes of categorization.
      Postmortem criteria have been employed to distinguish between degenerative and
      nondegenerative disorders, and specific hallmarks may be required to establish or
      confirm a diagnosis. Genetic features used for classification purposes include
      mode of inheritance and molecular genetic data, such as linkage to a known gene
      locus or identification of a specific genetic defect. A final classification
      scheme is based on alterations in molecular mechanisms (e.g. trinucleotide
      expansions) or protein function (e.g. channelopathies). Despite recent advances,
      it may not be possible to develop the 'ultimate' classification of movement
      disorders, and different patterns of lumping and splitting may be useful for the
      clinician, the pathologist or the geneticist/molecular biologist. Furthermore,
      certain individual cases with unique features may not fit into any particular
      category. Continued research by both clinicians and basic scientists is necessary
      in order to refine and redefine classification schemes of movement disorders.

PMID- 15868476
TI  - Treatment strategies in movement disorders.
AB  - Strategies in treatment of movement disorders are discussed with the illustration
      of three patients with dystonia. Pharmacotherapy can be applied in two ways: (1)
      a precise directed therapy, or (2) a 'shotgun' approach. Botulinum toxin is
      successfully injected in focal and segmental forms of movement disorders.
      Stereotactic neurosurgery can be considered in pharmacotherapy-resistant
      dystonias, but also in other forms of movement disorders. Intrathecal baclophen
      treatment by continuous infusion is only indicated in severe forms of spasticity.

PMID- 15868477
TI  - Antigenotoxic potential of glucomannan on four model test systems.
AB  - Antimutagenic, anticlastogenic, and bioprotective effect of polysaccharide
      glucomannan (GM) isolated from Candida utilis was evaluated in four model test
      systems. The antimutagenic effect of GM against 9-aminoacridine (9-AA)- and
      sodium azide (NaN3)-induced mutagenicity was revealed in the Salmonella
      typhimurium strains TA97 and TA100, respectively. GM showed anticlastogenic
      effect against N-nitroso-N'-methylurea (NMU) induced chromosome aberrations in
      the Vicia sativa assay. The bioprotective effect of GM co-treated with methyl
      methane-sulphonate (MMS) was also established in Chlamydomonas reinhardtii repair
      deficient strains uvs10 and uvs14. The statistically significant antimutagenic
      potential of GM was not proved against 4-nitro-quinoline-1-oxide (4-NQO)-induced
      mutagenicity in Saccharomyces cerevisiae D7 assay. It may be due to
      bioprotectivity of alpha-mannan and beta-glucan, which are integral part of S.
      cerevisiae cell walls. Due to the good water solubility, low molecular weight (30
      kDa), antimutagenic/anticlastogenic, and bioprotective activity against chemical
      compounds differing in mode of action, GM appears to be a promising natural
      protective (antimutagenic) agent.

PMID- 15868478
TI  - Speculations on the role of the microtubule network in glucocorticoid receptor
      signaling.
AB  - The glucocorticoid receptor (GR) is an important player in the life of a cell.
      This is underlined by a cohort of protein and nucleic acid structures interacting
      with the GR. Among many issues surrounding GR activity that are under active
      investigation, the role of microtubules (MTs) is still unclear. This article aims
      to evaluate the ayes and noes in favor of microtubule importance and then form a
      hypothesis on their function in GR activity.

PMID- 15868479
TI  - TNF-alpha expression patterns as potential molecular biomarker for human skin
      cells exposed to vesicant chemical warfare agents: sulfur mustard (HD) and
      Lewisite (L).
AB  - Studies were conducted to examine the effect of two vesicant chemical warfare
      agents (VCWA), one of them an arsenical, on cytokine gene expression in normal
      human epidermal keratinocyte (NHEK) cells. We tested 2,2'-dichlorethylsulfide
      (sulfur mustard, military designation HD) and 2,chlorovinyldichloroarsine
      (Lewisite, military designation L), which have significant differences in their
      chemical, physical, and toxicological properties. Human tumor necrosis factor
      alpha (hTNF-alpha) cytokine was detected by using the enzyme-linked immunosorbent
      assay, a protein multiplex immunoassay, Luminex100, and reverse transcription
      polymerase chain reaction (RT-PCR). The messenger RNA expression of hTNF-alpha
      was determined to provide a semi-quantitative analysis. HD-stimulated NHEK
      induced secretion of hTNF-alpha in a dose-dependent manner. Dose response effect
      of Lewisite decreased hTNF-alpha levels. Time-response data indicated that the
      maximum response for HD occurred at 24 h with an associated cytotoxic
      concentration of 10(-4) mol/L. NHEK cells stimulated with 10(-4) mol/L HD for 24
      h at 37 degrees C increased detectable levels of hTNF-alpha from 5 to 28 ng/ml at
      an index of cell viability between 85 to 93% as detected by Luminex100. Our
      results indicated that the increased levels of hTNF-alpha by HD are dependent on
      the primary cultures, cell densities, and chemical properties of the stimulation.
      Lewisite under the same conditions as HD caused a reduction of hTNF-alpha from
      control levels of 1.5 ng/ml to 0.3 ng/ml after stimulation (10(-4) mol/L), with
      an index of cell viability of reverse similar 34%. We analyzed the
      transcriptional of hTNF-alpha gene and found that HD (10(-6) to 10(-4) mol/L)
      activates hTNF-alpha gene in cultured NHEK and that L at 10(-6) to 10(-4) mol/L
      markedly reduces hTNF-alpha gene. We conclude that the pro-inflammatory mediator,
      hTNF-alpha, could be a potential biomarker for differentiating between exposure
      of HD or L.

PMID- 15868480
TI  - Impact of ethanol and acetaldehyde on DNA and cell viability of cultured
      neurones.
AB  - Ethanol consumption has long been associated with brain damage. However, the
      mechanism underlying this deleterious effect remains unclear. Among different
      hypotheses, acetaldehyde is regarded by certain authors as playing a major role
      in the expression of ethanol toxicity, but there are still some uncertainties
      about the exact nature of its implication. We therefore tried to characterize the
      profile of the alterations of neuronal viability and DNA integrity obtained after
      either a direct exposure to ethanol or to acetaldehyde. Ethanol at concentrations
      within the range of blood alcohol levels in intoxicated humans (< or = 100
      mmol/L) induced DNA alterations without any apparent effect on cell viability.
      Acetaldehyde (< or = 1000 micromol/L) can also induce DNA alterations but with a
      different profile of the DNA cellular alterations. The comparison between the
      distributions of the comet tail DNA indicated that ethanol induced strong breaks
      (tail DNA > or = 60 a.u.) generation whereas acetaldehyde rather induced lower
      breaks (20 < or = tail DNA < or = 50 a.u.) formation but affecting a greater
      number of neurones. Acetaldehyde had thus a different genotoxic potential which
      may suggest a different mode of action or a different cellular target.
      Furthermore, when a single 100 mmol/L ethanol exposure did not lead to any loss
      of cell viability, the addition of an inhibitor of aldehyde dehydrogenase was
      followed by a significant loss in viability. In contrast, the inhibition of
      catalase, which suppresses acetaldehyde synthesis, led to no reduced viability in
      the same exposure conditions. ROS also reduced viability, but this was observed
      only after both cytochrome P450 stimulation and catalase inhibition. These
      combined results could suggest that acetaldehyde may play a significant role in
      the expression of ethanol toxicity in brain.

PMID- 15868481
TI  - Low-level arsenite activates the transcription of genes involved in adipose
      differentiation.
AB  - In this study we analyzed gene expression in 3T3-F442A pre-adipocyte cells that
      differentiate in the presence of micro-molar arsenate concentration. Two
      concentrations of arsenite (As2O3, 0.25 micromol/L and 0.5 micromol/L) were
      applied for three days with and without insulin (170 nmol/L) and gene expressions
      were evaluated by quantitative RT-PCR. The genes included genes of oxidative
      stress responses: heme-oxygenase-1 (HO1) and the hypoxia inducible factor 1a
      (HIF1alpha), genes of cell-cycle: c-jun and Kruppel like factor 5 (KLF5), and
      genes that play important roles in adipose determination: a peroxisome
      proliferator-activated receptor (PPARgamma) and a CCAAT/ enhancer binding protein
      (C/EBPalpha). Arsenite induced the expression of HO1, HIF1alpha, KLF5, PPARgamma
      and C/EBPalpha. These results suggest that under condition of oxidative stress
      arsenite induces genes that are required for adipose differentiation.

PMID- 15868485
TI  - The Caco-2 cell line as a model of the intestinal barrier: influence of cell and
      culture-related factors on Caco-2 cell functional characteristics.
AB  - The human intestinal Caco-2 cell line has been extensively used over the last
      twenty years as a model of the intestinal barrier. The parental cell line,
      originally obtained from a human colon adenocarcinoma, undergoes in culture a
      process of spontaneous differentiation that leads to the formation of a monolayer
      of cells, expressing several morphological and functional characteristics of the
      mature enterocyte. Culture-related conditions were shown to influence the
      expression of these characteristics, in part due to the intrinsic heterogeneity
      of the parental cell line, leading to selection of sub-populations of cells
      becoming prominent in the culture. In addition, several clonal cell lines have
      been isolated from the parental line, exhibiting in general a more homogeneous
      expression of differentiation traits, while not always expressing all
      characteristics of the parental line. Culture-related conditions, as well as the
      different Caco-2 cell lines utilized in different laboratories, often make it
      extremely difficult to compare results in the literature. This review is aimed at
      summarizing recent, or previously unreviewed, data from the literature on the
      effects of culture-related factors and the influence of line sub-types (parental
      vs. different clonal lines) on the expression of differentiation traits important
      for the use of Caco-2 cells as a model of the absorptive and defensive properties
      of the intestinal mucosa. Since the use of Caco-2 cells has grown exponentially
      in recent years, it is particularly important to highlight these methodological
      aspects in order to promote the standardization and optimisation of this
      intestinal model.

PMID- 15868486
TI  - Effect of water-soluble fraction of cigarette smoke on human aortic endothelial
      cells--a proteomic approach.
AB  - Proteomic analysis is an important investigative tool used to systematically
      explore cellular proteins that are responsive to adverse environmental
      challenges. Tobacco smoking is the second major cause of death in the world. In
      this study, we utilized two-dimensional electrophoresis (2-DE) and mass
      spectrometry (MS) technologies to explore protein changes in human aortic
      endothelial cells (HAECs) in response to cigarette smoke extracts (CSE). Among
      389 individual proteins resolved using 2-DE, 43 had a 2- to 3-fold change in
      levels as measured by spot intensity and 32 had more than a 3-fold change.
      Sixteen of the 32 spots with sufficient amount of proteins were excised for
      identification by performing matrix-assisted laser desorption/ionization (MALDI)
      MS analysis. Using a peptide mass fingerprinting (PMF) to search the nrNCBI
      database, we identified all these 16 proteins, which were either increased (n =
      9) or decreased (n = 7) after CSE treatment. All these proteins have known
      functions, however, none have been reported to be altered after CSE treatment.
      The findings from our study suggest that utilizing a systemic investigative tool,
      such as the proteomic approach using 2-DE, may play an important role in
      discovering novel molecular mechanisms for cigarette smoking-induced pathological
      changes. Further investigation following the systemic discoveries must be further
      examined as they may potentially lead to new therapeutic approaches to smoking
      induced diseases - a health issue affecting everyone in the world.

PMID- 15868487
TI  - Vanadium inhibits DNA-protein cross-links and ameliorates surface level changes
      of aberrant crypt foci during 1,2-dimethylhydrazine induced rat colon
      carcinogenesis.
AB  - The trace mineral vanadium inhibits cancer development in a variety of
      experimental animal models. The present study was to gain insight into a putative
      anticancer effect of vanadium in a rat model of colon carcinogenesis. The in vivo
      study was intended to clarify the effect of vanadium on DNA-protein cross-links
      (DPC), surface level changes of aberrant crypt foci (ACF) and biotransformation
      status during 1,2-dimethylhydrazine (1,2-DMH) induced preneoplastic rat colon
      carcinogenesis. The comet assay showed statistically higher mean base values of
      DNA-protein mass (p<0.01) and mean frequencies of tailed cells (p<0.001) in the
      carcinogen-induced group after treatment with proteinase K. Treatment with
      vanadium in the form of ammonium monovanadate supplemented ad libitum in drinking
      water for the entire experimental period caused a significant (p<0.02) reduction
      (40%) in DNA-protein cross-links in colon cells. Further, the biotransformation
      status of vanadium was ascertained measuring the drug metabolising enzymes,
      glutathione S-transferase (GST) and cytochrome P-450 (Cyt P-450). Significantly,
      there was an increase in glutathione S-transferase and cytochrome P-450 levels
      (p<0.01 and p<0.02, respectively) in rats supplemented with vanadium as compared
      to their carcinogen controls. As an endpoint marker, we also evaluated the effect
      of vanadium on surface level changes of aberrant crypt foci induced by 1,2-DMH by
      scanning electron microscopy. Animals induced with 1,2-DMH and supplemented with
      vanadium showed a marked improvement in colonic architecture with less number of
      aberrant crypt foci in contrast to the animals induced with 1,2-DMH alone,
      thereby exhibiting its anti-carcinogenicity by modulating the markers studied
      herein.

PMID- 15868488
TI  - Vitamin E protects against acetone-induced oxidative stress in rat red blood
      cells.
AB  - Acetone may induce oxidative stress leading to disturbance of the biochemical and
      physiological functions of red blood cells (RBCs) thereby affecting membrane
      integrity. Vitamin E (vit E) is believed to function as an antioxidant in vivo
      protecting membranes from lipid peroxidation. The aim of the present study was
      the evaluation of possible protective effects of vit E treatment against acetone
      induced oxidative stress in rat RBCs. Thirty healthy male Wistar albino rats,
      weighing 200-230 g and averaging 12 weeks old were randomly allotted into one of
      three experimental groups: Control (A), acetone-treated (B) and acetone + vit E
      treated groups (C), each containing ten animals. Group A received only drinking
      water. Acetone, 5% (v/v), was given with drinking water to B and C groups. In
      addition, C group received vit E dose of 200 mg/kg/day i.m. The experiment
      continued for 10 days. At the end of the 10th day, the blood samples were
      obtained for biochemical and morphological investigation. Acetone treatment
      resulted in RBC membrane destruction and hemolysis, increased thiobarbituric acid
      reactive substance (TBARS) levels in plasma and RBC, and decreased RBC vit E
      levels. Vit E treatment decreased elevated TBARS levels in plasma and RBC and
      also increased reduced RBC vit E levels, and prevented RBC membrane destruction
      and hemolysis. In conclusion, vit E treatment appears to be beneficial in
      preventing acetone-induced oxidative RBC damage, and therefore, it can improve
      RBC rheology.

PMID- 15868489
TI  - Influence of green tea on surface charge density and phospholipids composition of
      erythrocytes membrane in ethanol intoxicated rats.
AB  - Ethanol is oxidized to acetaldehyde and then to acetic acid and these processes
      are accompanied by free radical generation. This paper reports the effect of
      green tea on electric charge and phospholipids composition of erythrocytes
      membrane from rats intoxicated with ethanol. Electrophoresis technique and HPLC
      have been applied to above-mentioned studies. Ethanol administration caused
      increase in erythrocyte membrane surface charge density and phospholipid
      composition. Ingestion of green tea with ethanol partially prevented changes in
      structure and function of membrane caused by chronic ethanol intoxication.

PMID- 15868491
TI  - Good colorectal cancer surgery.
AB  - Adenocarcinoma of the colon and rectum is currently diagnosed in about 783,000
      new cases annually and 437,000 patients will die of the disease each year
      worldwide. Colorectal cancer presents as an emergency situation (obstruction,
      bleeding or perforation) in approximately 25% of cases and with more or less
      obvious chronic symptoms in the rest of cases. Rectal cancer patients, with a T1
      tumour can be offered local excision whereas patients with more advanced cancer
      must be offered a more radical abdominal procedure. In large bulky tumours (T3 or
      definitely T4), MRI should guide the choice of preoperative radiotherapy. Three
      major indications for radiotherapy are reduction of local recurrences in mobile
      rectal cancer in order to improve survival, down-staging of the tumour in primary
      irresectable tumours, and downsizing of low-lying tumours in an attempt to
      perform a sphincter-saving procedure. The surgical strategy is to remove the
      tumour-bearing bowel segment with, if possible, a locoregional curative
      procedure, to restorate bowel continuity, and to ensure an optimal quality of
      life. In most situations, it is possible to achieve local radical resection. In
      rectal cancer surgery, the main problem is to stick to the embryological planes
      during the whole procedure. The whole mesorectum is taken out as a packet down to
      the level of division. This TME procedure dramatically reduced the local
      recurrence rate to 3%-7%. Surgeon case volume may be an important factor in
      cancer surgery success. Laparoscopic surgery for colorectal cancer has stimulated
      a great deal of interest in recent years, but there are concerns regarding this
      type of surgery. In conclusion, modern surgery for colorectal cancer is a well
      defined technique where the anatomical planes have to be identified. Care must be
      taken to learn all the essential steps. Data from the literature strongly support
      that the surgeon is the most important factor for an excellent outcome.

PMID- 15868492
TI  - Stoma formation for fecal diversion: a plea for the laparoscopic approach.
AB  - BACKGROUND: The aim of this study was to assess the results of laparoscopic stoma
      creation for fecal diversion, specifically focussing on feasibility, safety, and
      efficacy, as well as indications and techniques. METHODS: Within a 10-year
      period, all patients requiring laparoscopic stoma creation were evaluated
      prospectively. Patients' profiles and indications, procedures and results of
      operation, conversion, morbidity, mortality and short-term complications (stoma
      related, laparoscopy-associated) were analyzed. RESULTS: A total of 80 patients
      (39 males, 41 females) with a mean age of 55.5 years (range, 17-91) underwent
      laparoscopic stoma creation. Most common indications were unresectable advanced
      colorectal cancer (n=20), pelvic malignant cancer (e. g. ovarian, cervix and
      prostate cancer, n=16), and perianal Crohn's disease with complex fistulas
      (n=16). Only in one female patient with pelvic malignant disease was the
      procedure converted to laparotomy due to obesity (conversion rate, 1.3%). 79
      patients underwent laparoscopic stoma creation (completion rate, 98.7%) including
      loop ileostomy (n=30), loop sigmoid colostomy (n=40) and end sigmoid colostomy
      (n=9). Postoperative complications were documented in 9 patients (overall
      morbidity rate, 11.4%), including 4 minor complications treated conservatively (2
      cases of prolonged atonia and 1 case each of pneumonia and urinary tract
      infection) and 5 major complications requiring reoperation (reoperation rate,
      6.3%): one parastomal abscess (drainage), one stoma retraction following rod
      dislocation (laparoscopic stoma recreation), small bowel obstruction in two
      patients (small bowel resection), one port-site hernia (fascial closure), and
      hemorrhage (managed by re-laparoscopy). Mean operation time was 74 min (range, 30
      245 min). Mean blood loss volume was 80 ml (range, 30-400 ml). Patients were
      discharged from hospital after a mean of 10.3 days (range, 3-47). Within a 1-year
      follow-up, no further stoma complications were documented. CONCLUSIONS: The
      advantages of laparoscopic stoma creation are low morbidity and reoperation
      rates, and no procedure-related mortality; our results suggest that laparoscopic
      stoma creation for fecal diversion is safe, feasible and effective. Therefore, at
      our institution, laparoscopic stoma creation is the method of choice for fecal
      diversion.

PMID- 15868493
TI  - Different role of the colonic pouch for low anterior resection and coloanal
      anastomosis.
AB  - BACKGROUND: Functional outcome after sphincter-saving operations can be improved
      by colonic pouch compared to the straight procedure. However, it is not clear
      whether the colonic pouch has a different behavior in patients treated by low
      anterior resection with colorectal (LAR) or coloanal anastomosis (CAA). METHODS:
      We evaluated the 1-year results of 75 patients who underwent a sphincter-saving
      operation for rectal carcinoma or villous tumor of the middle or lower third of
      the rectum: 18 patients underwent coloanal anastomosis (CAA), in 13 patients we
      performed a coloanal anastomosis with a colonic pouch (PCAA), 20 patients had low
      anterior resection (LAR) and 24 had LAR with pouch construction (PLAR). The two
      groups of patients were similar in terms of age and gender. Anorectal function
      was assessed 12 months after the initial operation by an interview and anorectal
      manometry. RESULTS: One year after surgery, the daily mean number of defecations
      was significantly higher in the LAR group than in the other groups (2.0+/-1.5 in
      CAA group, 2.2+/-1.0 in PCAA, 2.3+/-1.8 in PLAR, 4.1+/-0.7 in LAR; p<0.05).
      Frequent soiling was observed in all the groups except PLAR. A lower degree of
      incontinence and a lower frequency of urgency were found in PCAA than in CAA.
      There were no differences in anal resting pressure and squeeze pressure among the
      various groups. Greater distensibility and compliance of the neorectum were
      observed in CAA, PCAA and PLAR compared to LAR, respectively 8.5+/-7.0 ml
      air/mmHg for CAA, 8.7+/-5.0 ml air/mmHg for PCAA, 6.3+/-4.0 ml air/mmHg for PLAR
      and 3.1+/-2.7 ml air/mmHg for LAR. A significant inverse linear correlation was
      present between the mean daily number of defecations and compliance. No
      difference in sense of incomplete evacuation was observed among the groups of
      patients. CONCLUSIONS: Colonic J-pouch provides an advantage over straight
      anastomosis in sphincter-saving operations by reducing the daily number of
      defecations, and the frequencies of fecal soiling and urgency. The role of the
      pouch seems to be different in LAR compared to CAA. In fact, in LAR the pouch
      increases compliance and consequently decreases the daily number of defecations.
      In CAA, the pouch does not reduce the number of defecations or the compliance,
      but reduces the frequency of fecal soiling and urgency.

PMID- 15868494
TI  - Treatment of pilonidal sinus by phenol application and factors affecting the
      recurrence.
AB  - BACKGROUND: Phenol injection, a less invasive method, has become more popular for
      the treatment of sinus pilonidalis. Recurrence rates after the use of phenol have
      been reported to be less than those after other surgical methods. METHODS: In
      this study, we applied 80% phenol to 143 patients with sinus pilonidalis.
      Patients were reevaluated at 1, 3, 6, 12 and 24 months after the phenolization
      procedure to search for any recurrences. Age, sex, skin color, occupation, hair
      distribution, complaints, macroscopic characteristics of the lesion, pouch
      volume, microbiological yield, complications of phenol injection, healing time,
      and recurrences were determined. RESULTS: The mean follow-up period was 24 months
      and the recurrence rate was 8.3% (12 of 143 patients). Volume of the sinus tract
      and number of sinus orifices were determined to be the factors significantly
      affecting recurrences (p<0.05). CONCLUSIONS: Injection of 80% phenol is an ideal
      approach for the conservative treatment of sinus pilonidalis. This study confirms
      that this is an effective and costless method with low recurrence rates.

PMID- 15868495
TI  - New screening technique for sacral nerve stimulation under local anaesthesia.
AB  - BACKGROUND: The purpose of this study was to assess the influence of the type of
      anaesthesia (local vs. general) and of the electrode used (test electrode vs.
      tined lead) on a successful screening period. METHODS: Between May 2001 and
      January 2004, we performed 25 percutaneous nerve evaluation (PNE) tests in 20
      patients (11 women). The first 15 PNE tests were followed by introducing a
      conventional electrode, and since 2003 by a tined lead electrode. Success was
      defined as reduction of symptoms by more than 50%. RESULTS: A stimulator was
      implanted in 13 (68%) patients, including 4 of 14 screened with the conventional
      electrode and 9 of 10 screened with tined lead electrode (p=0.005). Eleven (44%)
      of the PNE tests were done under local anaesthesia, but the success rate was not
      influenced by the type of anaesthesia (local 46% vs. general 61%, p=0.682).
      CONCLUSIONS: PNE testing and implantation of the tined lead electrode can be
      easily performed at the same time under local anaesthesia. The use of the new
      tined lead electrode significantly increased the success rate for the screening
      phase.

PMID- 15868496
TI  - Comparison of cecal abrasion and multiple-abrasion models in generating intra
      abdominal adhesions for animal studies.
AB  - BACKGROUND: The formation of postoperative adhesions is a common problem in
      abdominal surgery that may lead to serious complications. Appropriate animal
      adhesion models are essential for the investigation of adhesiogenesis and the
      development of new anti-adhesive products. Although animal models have been
      developed to study the process of adhesion formation in the abdomen, they are not
      effective in generating adhesions located over small bowel where adhesions are
      most commonly observed in clinical practice. METHODS: Twenty-nine Sprague Dawley
      rats were subjected to standardized cecal abrasion (group 1; n=9), or two types
      of multiple abrasion, in which cecal and 3 or 5 abrasions were performed on small
      bowel (group 2, n=10; and group 3, n=10). An observer blinded to the
      randomization assessed the difficulty of adhesiolysis on a 6-point scale, and the
      locations of the adhesions were recorded 21 days after the initial surgery.
      RESULTS: Adhesiolysis was significantly more difficult in group 3 than in group 1
      (p=0.01). The number of animals that had adhesions between the small bowel
      segments and the total number of locations where small bowel adhered were
      significantly greater in group 2 and 3 than in group 1 (p<0.05 for all
      comparisons). CONCLUSIONS: Abrasions to the small bowel created consistent
      adhesions that have clinical characteristics of intra-abdominal adhesions as
      compared to the standard cecal abrasion model and that can be used in future
      animal studies on adhesions.

PMID- 15868497
TI  - Anterolateral rectopexy for correction of rectoceles leads to good anatomical but
      poor functional results.
AB  - BACKGROUND: Several different surgical repair procedures for symptomatic
      rectocele have been described with variable results. In our clinic, a modified
      anterolateral rectopexy is used. In this article we evaluate our results, with
      emphasis on patient satisfaction. METHODS: From 2001 until 2003, twenty patients
      with a symptomatic rectocele were treated by anterolateral rectopexy. The
      preoperative dynamic defecogram and anorectal complaints were analyzed and
      compared to postoperative outcome via a standardized questionnaire. RESULTS:
      After surgery, all rectoceles were restored as shown by postoperative defecogram.
      Anorectal symptoms (incomplete evacuation, continuous urge, prolapse, digital
      evacuation) were improved in 40%. As new-onset symptoms, dyspareunia (50%),
      digital support (55%) and incomplete evacuation (75%) were mentioned frequently.
      Most of the patients with larger rectoceles (>3.5 cm) had increased anorectal
      complaints after surgery. CONCLUSIONS: Anterolateral rectopexy for treatment of
      rectocele give limited improvement of anorectal complaints. Besides, many
      patients developed new complaints postoperatively and hence overall satisfaction
      was low.

PMID- 15868498
TI  - Failure of medical treatment in an adult cystic fibrosis patient with meconium
      ileus equivalent.
AB  - Meconium ileus equivalent is one of the lesser-known manifestations of cystic
      fibrosis. It manifests as distant small bowel obstruction caused by meconium-like
      stool plugs and occurs mostly in adult patients. With the improved overall
      survival of patients with cystic fibrosis, general surgeons may encounter this
      condition more often in the future. We treated a 19-year-old woman with cystic
      fibrosis who presented with complete distal small bowel obstruction. Medical
      therapy with Gastrografin and N-acetylcysteine failed to resolve the obstruction.
      At surgery, a meconium-like plug in the distal ileum was manually pushed into the
      colon with subsequent relief of symptoms. Meconium ileus equivalent should be
      considered and treated in cystic fibrosis patients presenting with small bowel
      obstruction.

PMID- 15868499
TI  - Anorectal atresia treated with non-continent pull through and artificial bowel
      sphincter: a case report.
AB  - Anorectal atresia, which is classified as a low anorectal malformation, is
      characterised by the absence of the anal verge and by variable rectal atresia. In
      some cases, which have been classified as rectal agenesis, the atresia is
      associated with the absence of the internal sphincter. The therapeutic options
      are definitely surgical, aiming to relieve the bowel occlusion and to restore
      faecal continence by lowering the cul-de-sac to the perineum. We present the case
      of an adult patient with congenital rectal agenesis, double fistula (cul-de-sac
      urethra and cul-de-sac-perineum) and caecostomy since birth. The patient was
      treated with a resection of sigmoid-rectum for the presence of a 20-cm faecaloma
      in the cul-de-sac, with a non-continent pull-through, and with implantation of an
      artificial bowel sphincter. Despite some difficulties in managing the device and
      a slight symptomatic mucosal prolapse, the results after 30 months have so far
      satisfied both the patient and the medical staff, especially in consideration of
      the limited number of alternative therapies.

PMID- 15868500
TI  - The utilization of intraluminal formalin for intractable rectal haemorrhage in
      advanced rectal cancer: a case report.
AB  - A patient with a metastatic fixed low rectal carcinoma presented severe rectal
      bleeding requiring massive transfusion over with a 36-hour period. Bleeding was
      controlled with the instillation of a 4% intrarectal formalin solution permitting
      the completion of a course of neoadjuvant chemoradiotherapy. This technique has
      been reserved for intractable transfusion-dependent radiation proctitis and is
      presented as a primary alternative in severe rectal bleeding from inoperable
      rectal cancer.

PMID- 15868501
TI  - A case of perforation and fistula formation resulting from metallic stent for
      sigmoid colon stricture in Crohn's disease.
AB  - A 52-year-old male was diagnosed with Crohn's disease at the age of 25 years.
      Thereafter, he underwent three operations for intestinal strictures or fistula. A
      self-expanding metallic stent was inserted into the sigmoid colon stricture
      endoscopically in November 1999. Thirty two months later, he presented left lower
      abdominal pain. Endoscopic and radiographic examinations demonstrated perforation
      of the stent and ileosigmoid fistula. Laparotomy revealed an inflammatory mass
      around the sigmoid colon, and the wire frame of the metallic stent had penetrated
      the colonic wall and had fistulized to the ileum. The affected sigmoid colon was
      resected and low anterior resection and ileostomy were performed. Metallic stent
      for intestinal stricture of Crohn's disease with active ulceration may postpone
      surgery temporarily but can be a potentially dangerous procedure.

PMID- 15868502
TI  - Haemorrhoidectomy as a one-day surgical procedure: modified Ferguson technique.
AB  - Modification of Ferguson haemorrhoidectomy had been started because it was easier
      to ligate the haemorrhoidal pedicle with a rubber band instead of using the
      stitch. There is no need to use a retractor for such a procedure as it would
      cause discomfort to the patient when only infiltrative anaesthesia for one or two
      haemorrhoidal complexes was given. In the period from 1994 to 1999, we performed
      398 haemorrhoidectomies as a one-day surgical procedure under local infiltrative
      anaesthesia. The examination follow-ups of the patients were performed and
      medical charts were reviewed. Early postoperative complications were rare:
      haemorrhage occurred in 1.8%, urine retention in 0.5%, high temperature in 1.3%
      and temporary incontinence in 0.3%. Overall, 28 patients (7%) had additional
      treatment for residual haemorrhoid problems 5-10 years after the primary
      haemorrhoidectomy was performed. We believe that our modified technique is a
      welcome alternative to the one-day surgical practice.

PMID- 15868503
TI  - Anal melanoma in the era of sentinel lymph node mapping: a diagnostic and
      therapeutic challenge.
AB  - Melanoma of the anal canal is a rare malignancy that often has an atypical
      presentation. Locoregional metastases, which are often present at the initial
      presentation, may occur in both groin and pelvic lymph nodes, but the utility of
      lymph node dissection remains unknown. We explored the possibility of applying
      the technique of sentinel lymph node (SLN) mapping to anal melanoma. SLN mapping
      was performed in 2 patients with anal melanoma. Radioactive tracer and blue dye
      were injected around the lesions. The SLN was identified pre-operatively by
      lymphoscintigraphy, and at surgery with a hand-held gamma detector and by
      visualization of the dye. The SLN was identified in both patients, only in the
      groin in one and only in the presacral region in the other. One patient had a
      wide local excision of the anal lesion with house flap anoplasty, while the other
      had abdominoperineal resection with total mesorectal excision. There were no SLN
      metastases in either patient. The technique of SLN mapping and biopsy is easily
      adapted to surgery for malignant melanoma of the anus. SLN mapping and biopsy
      could aid in planning surgical strategy, but definitive conclusions may only be
      reached after more experience has been acquired.

PMID- 15868504
TI  - Transanal repair of rectocele and full rectal mucosectomy with one circular
      stapler: a novel surgical technique.
AB  - We present a new surgical stapling technique for treatment of rectocele when
      associated with internal mucosal prolapse or haemorrhoids using only one circular
      mechanical stapler. Eight female patients, mean age 53 years (range, 42-70),
      complaining of obstructed defecation with vaginal digitation because of rectocele
      associated with internal mucosal prolapse underwent transanal repair of rectocele
      and rectal mucosectomy using one circular stapler between April and July 2004. A
      running horizontal mattress suture was placed through the base of the rectocele
      including mucosa, submucosa and the muscle layer of the whole anterior anorectal
      junction wall. The prolapsed mucosa and the muscular layer were then excised with
      an electrical scapel. A continuous pursestring rectal mucosa suture was placed
      0.5 cm before the previous anterior mucosa and muscle layers resected wound,
      including the anorectal junction wall which was kept separate from the posterior
      vaginal wall by a Babcock forceps. Posteriorly, the pursestring suture included
      only mucosal and submucosal layers. The stapled suture was positioned between
      normal anterior rectal wall and the anal canal, 0.5 cm above the pectinate line.
      The stapler was then closed, fired and withdrawn. One patient complained of a
      perianal hematoma on the seventh postoperative day, requiring surgical excision.
      Postoperative defecography showed correction of the rectocele and outlet
      obstruction disappeared in all patients. This novel combined manual-stapled
      technique for rectocele and rectal internal mucosal prolapse seems to be a safe
      procedure and the preliminary results are encouraging. Further investigations
      have to be performed to assess long-term outcome in a larger number of patients.

PMID- 15868505
TI  - Endoanal ultrasound-guided needle drainage of intersphincteric abscess.
AB  - Traditional management of intersphincteric abscess is by incision and drainage
      involving division of fibres of the internal sphincter. Here, a less invasive
      method is described. Three patients with intersphincteric abscess identified by
      endoanal sonography were treated by ultrasound-guided needle aspiration under
      anaesthesia. None of the patients had complications or required postoperative
      wound care. All patients remained asymptomatic at a mean follow-up of 15.7 months
      (range, 12-18 months). Endoanal ultrasound-guided aspiration is a simple and safe
      method for the treatment of intersphincteric abscess.

PMID- 15868506
TI  - Endosonographic pattern of solitary polypoid rectal ulcer.

PMID- 15868508
TI  - Invited comment. Long term outcome following loose-seton technique for external
      sphincter preservation in complex anal fistula.

PMID- 15868509
TI  - The last images. Pneumoretroperitoneum, pneumomediastinum and subcutaneous
      emphysema of the neck after stapled hemorrhoidopexy.

PMID- 15868510
TI  - The last images. Fecal incontinence after stapled transanal rectotomy managed
      with Durasphere injection.

PMID- 15868516
TI  - When is intraoperative transesophageal echocardiography indicated?

PMID- 15868517
TI  - Transesophageal echocardiography-related gastrointestinal complications in
      cardiac surgical patients.
AB  - OBJECTIVE: The aim of this audit was to determine the incidence of major
      gastrointestinal (GI) complications associated with intraoperative
      transesophageal echocardiography (TEE) in adult cardiac surgical patients in this
      institution. DESIGN: Retrospective database audit. SETTING: University-affiliated
      teaching hospital. PARTICIPANTS: Eight hundred fifty-nine consecutive cardiac
      surgical patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The
      records of all patients who developed a major upper GI complication within 30
      days of cardiac surgery between January 2001 and May 2003 were examined. The
      patients were identified by cross-referencing cardiac surgery and endoscopy
      databases. A major GI complication was defined as a perforation of the esophagus
      or stomach or upper GI bleeding requiring transfusion, endoscopic, or surgical
      intervention. Early presentation was defined as <24 hours; late presentation was
      defined as >24 hours. During the audit period, 859 patients underwent cardiac
      surgery. Five hundred sixteen patients had cardiac surgery with TEE (group 1),
      and 343 patients had cardiac surgery without TEE (group 2). Six patients were
      identified, 1.2% (95% confidence interval [CI], CI, 0.5%-2.5%) in group 1 who had
      a major upper GI complication consistent with TEE injury. Two patients, 0.38%
      (95% CI, 0.05%-1.40%), presented early, and 4 patients, 0.76% (95% CI, 0.21%
      1.98%), presented late. One patient in group 2 developed a major upper GI
      complication, 0.29% (95% CI, 0.01%-1.6%). CONCLUSION: The incidence of major GI
      complications attributed to TEE in this group of cardiac surgical patients was
      higher than previously reported. Late presentation was more common than early
      presentation. Previous studies that have not included late presentations may have
      underestimated the true incidence of major GI complications related to TEE.

PMID- 15868518
TI  - Analysis of the interatrial septum by transesophageal echocardiography in adult
      cardiac surgical patients: anatomic variants and correlation with patent foramen
      ovale.
AB  - OBJECTIVES: The purpose of this study was to document the perioperative
      prevalence of anatomic variants of the interatrial septum (IAS), to classify
      atrial septal aneurysm based on mobility pattern, and to correlate anatomic
      variants of IAS with patent foramen ovale (PFO). DESIGN: A prospective
      observational study. SETTING: University hospital (single institution).
      PARTICIPANTS: Patients presenting for cardiac surgery requiring transesophageal
      echocardiography. INTERVENTIONS: Multiplane TEE in 2 atrial views with color-flow
      Doppler and contrast echocardiography with a provocative respiratory maneuver.
      MEASUREMENTS AND MAIN RESULTS: The cohort size was 206. PFO prevalence was 30.1%.
      The prevalence of IAS lipomatous hypertrophy was 43.2%, atrial septal flap (ASF)
      43.2%, and atrial septal aneurysm (ASA) 28.6%. ASF and ASA were significantly ( p
      < 0.05) associated with PFO. Selected ASA subtypes are significantly associated
      with PFO ( p < 0.05). CONCLUSIONS: IAS anatomic variants are common in adult
      cardiac surgical patients undergoing multiplane TEE. The presence of ASF and ASA
      predicts enhanced PFO detection. ASA mobility patterns significantly correlate (
      p < 0.05) with the presence of PFO.

PMID- 15868519
TI  - National survey regarding the management of an intraoperatively diagnosed patent
      foramen ovale during coronary artery bypass graft surgery.
AB  - OBJECTIVE: With the increased use of intraoperative transesophageal
      echocardiography (TEE), patent foramen ovale (PFO) has become a common finding
      during routine coronary artery bypass graft (CABG) surgery. This survey was
      designed to study potential differences in the management of intraoperatively
      diagnosed PFO. DESIGN: A written survey. SETTING: US university and community
      hospitals. PARTICIPANTS: The authors randomly selected 50% of US cardiac surgeons
      listed in the Cardiothoracic Surgery Network Database (n = 734). INTERVENTIONS: A
      written survey was mailed to the participants. The survey questions included
      respondents' use of TEE during CABG surgery, examination for a PFO with TEE, and
      management of intraoperatively diagnosed PFO in the CABG surgery. MEASUREMENTS
      AND MAIN RESULTS: Overall, 64% of individuals (468/734) responded to the survey
      request. TEE is available in the primary institution of 98.6% of respondents and
      used to search for a PFO in approximately one third of all CABG surgeries. During
      planned on-pump CABG surgery, 27.9% of respondents always close an
      intraoperatively diagnosed PFO, whereas 10.2% of respondents never close an
      intraoperatively diagnosed PFO. During planned off-pump CABG surgery, 27.6% of
      surgeons never change their plan, and 11% of respondents always convert the
      procedure to on-pump CABG to close the PFO. The majority of respondents decide
      whether to close a PFO based on the size of the PFO, the right atrial pressure,
      and a history of possible paradoxical embolism. CONCLUSIONS: In the United
      States, TEE is used extensively during CABG surgery. There is significant
      variability in how intraoperatively diagnosed PFO is managed during CABG surgery.

PMID- 15868520
TI  - Feasibility and potential clinical utility of goal-directed transthoracic
      echocardiography performed by noncardiologist intensivists using a small hand
      carried device (SonoHeart) in critically ill patients.
AB  - OBJECTIVE: This study was designed to assess the clinical applicability of a
      small, handheld, portable transthoracic echocardiography device by
      noncardiologist intensivists. DESIGN: Prospective, observational study. After 10
      one-hour tutorials, intensivists performed a limited transthoracic
      echocardiography (TTE) (2-4 views, without Doppler or M-mode) examination with
      the 5.6-lb SonoHeart Echo System (SonoSite, Bethell, WA) on critically ill
      patients admitted to the surgical intensive care unit. After initial cardiac
      clinical assessment in 90 patients, a limited TTE was performed by an intensivist
      to assess left ventricular (LV) function and LV volume status. Each study was
      immediately reviewed and repeated by an echocardiographer to determine the
      technical quality of the TTE and the accuracy of the intensivist's
      interpretation. Data were analyzed and presented in proportions using descriptive
      statistics. SETTING: Surgical intensive care unit of an academic medical center.
      PARTICIPANTS: Ninety critically ill adult patients. INTERVENTIONS: After initial
      cardiac clinical assessment, a limited TTE was performed by an intensivist to
      assess LV size and function, to rule out significant pericardial effusions, and
      to estimate circulatory volume. RESULTS: Intensivists successfully performed a
      diagnostic limited TTE in 94% of patients and interpreted their studies correctly
      in 84%. Limited TTE provided new cardiac information and changed management in
      37% of patients. TTE added useful information in an additional 47% of patients
      but did not alter immediate management. The mean "goal-directed TTE" acquisition
      time was 10.5 +/- 4.2 minutes. CONCLUSION: After a brief formal training in using
      this handheld echocardiographic system in intensive care unit patients, surgical
      intensivists successfully performed and correctly interpreted a limited TTE in
      critically ill patients. Limited TTE provided new information and altered
      management in a significant number of patients. This study supports incorporating
      bedside goal-directed, limited TTE into intensivists' training programs.

PMID- 15868521
TI  - Cardiac output monitoring using a brachial arterial catheter during off-pump
      coronary artery bypass grafting.
AB  - OBJECTIVE: To investigate the accuracy of cardiac output measurements by
      transpulmonary thermodilution and pulse contour analysis using a brachial
      arterial catheter. STUDY DESIGN: Criterion standard study. SETTING: University
      hospital, single institution. POPULATION: Twenty-three adult patients undergoing
      off-pump coronary artery bypass grafting. MEASUREMENTS AND MAIN RESULTS: Cardiac
      output was measured with a thermistor-tipped brachial arterial catheter using
      pulse contour analysis (COpc) and transpulmonary thermodilution (COba), which
      serves to calibrate COpc in the system tested. Both methods were compared
      separately with standard pulmonary artery thermodilution (COpa). COba was closely
      correlated with COpa (r = 0.93, p < 0.001). Bland-Altman analysis showed a bias
      of 0.91 L/min with limits of agreement of +/-0.98 L/min. COpc was also closely
      correlated (r = 0.80, p < 0.001) with COpa and was found to have a bias of 1.08
      L/min with limits of agreement of +/-1.50 L/min. During the surgical procedure,
      changes in COpa from baseline were closely correlated with changes in COba (r =
      0.90, p < 0.01) and COpc (r = 0.81, p < 0.01). CONCLUSIONS: The brachial arterial
      access allows a reliable assessment of cardiac output by transpulmonary
      thermodilution and pulse contour analysis in patients undergoing off-pump
      coronary artery bypass grafting.

PMID- 15868522
TI  - Analysis of diastolic function in patients undergoing aortic aneurysm repair and
      impact on hemodynamic response to aortic cross-clamping.
AB  - OBJECTIVES: The purpose of this study was to analyze left ventricular diastolic
      function in patients undergoing aortic aneurysm repair and to investigate the
      effects of laparotomy and aortic cross-clamping on diastolic function. DESIGN:
      Prospective clinical study. SETTING: University hospital. PARTICIPANTS: Forty
      five consecutive patients undergoing open aortic aneurysm repair. INTERVENTIONS:
      Left ventricular diastolic function and hemodynamic variables were evaluated
      using transesophageal Doppler echocardiography and a pulmonary artery catheter at
      baseline, after laparotomy, and at 1 and 10 minutes after cross-clamping.
      Diastolic function was determined by Doppler derivatives of mitral inflow (E/A
      ratio, deceleration time of early inflow) and pulmonary venous flow (S/D ratio).
      MEASUREMENTS AND MAIN RESULTS: Twenty of 39 patients revealed signs of diastolic
      dysfunction at baseline. Of these 20 patients, 14 displayed delayed relaxation
      and 6 displayed a pseudonormal filling pattern. Patients with pseudonormal
      filling exhibited a lower stroke volume (p = 0.02) and cardiac index (p < 0.01)
      in comparison to patients with normal diastolic function. Laparotomy was
      associated with an improvement of diastolic function in 9 of 20 patients with
      preexisting diastolic dysfunction. Only 3 patients suffered impairment of
      diastolic function after cross-clamping. The hemodynamic response to cross
      clamping did not differ between patients with normal and abnormal diastolic
      function. CONCLUSIONS: About 50% of patients undergoing aortic aneurysm repair
      exhibit signs of diastolic dysfunction. The majority of these patients showed
      delayed relaxation. Patients with pseudonormal filling displayed a significantly
      lower cardiac index. Laparotomy resulted in an improvement in diastolic function
      in about half of patients with preexisting diastolic dysfunction. The effects of
      cross-clamping on diastolic function are minimal.

PMID- 15868523
TI  - Normobaric hyperoxia reduces cardiac index in patients after coronary artery
      bypass surgery.
AB  - OBJECTIVE: The purpose of this study was to assess the hemodynamic changes in
      response to normobaric hyperoxia in patients immediately after coronary artery
      bypass surgery. DESIGN: Observational study. SETTING: Single-center university
      hospital. PARTICIPANTS: Patients immediately after coronary artery bypass
      surgery. INTERVENTION: Change of fractional inspired oxygen concentration from
      baseline (< or =0.60) to 1.0 and return to baseline. MEASUREMENTS AND MAIN
      RESULTS: Cardiovascular changes were assessed with a lithium dilution technique.
      Cardiac index decreased from 2.82 to 2.52 L/min/m2 (10.6%). Heart rate decreased
      from 85.9 to 82.5 beats/min (4.0%), and the systemic vascular resistance index
      increased from 1,858 to 2,304 dyne/s/cm5/m2 (24.1%). Stroke index or mean
      arterial pressure did not change significantly. On reducing the FIO2 from 1.0 to
      the baseline FIO2 , there was significant reversal of the previous changes in
      heart rate and systemic vascular resistance. Heart rate increased from 82.5 to
      84.0 beats/min (1.8%), and the systemic vascular index decreased from 2304 to
      1932 dyne/s/cm5/m2 (16.1%). The cardiac output did not return to baseline, and
      the mean arterial pressure decreased from 69.6 to 64.4 mmHg (7.6%). CONCLUSIONS:
      Exposing patients after coronary artery surgery to hyperoxia induces significant
      hemodynamic changes.

PMID- 15868524
TI  - Immediate extubation after aortic valve surgery using high thoracic epidural
      analgesia or opioid-based analgesia.
AB  - OBJECTIVE: Fast-track anesthesia has gained widespread use in cardiac centers
      around the world. No study has been published focusing on immediate extubation
      after aortic valve surgery. This study examines the feasibility and hemodynamic
      stability of immediate extubation after simple or combined aortic valve surgery
      using either thoracic epidural analgesia or opioid-based analgesia. DESIGN:
      Prospective audit, pilot study. SETTING: Single-institution university medical
      center. PARTICIPANTS: Adult patients undergoing aortic valve replacement (N =
      45). INTERVENTIONS: Forty-five patients undergoing aortic valve surgery with an
      ejection fraction of more than 30% were included in this prospective audit.
      Induction of anesthesia was done using fentanyl, 2 to 4 mug/kg, propofol, 1 to 2
      mg/kg, and endotracheal intubation facilitated by rocuronium; anesthesia was
      maintained using sevoflurane titrated according to bispectral index (BIS [BIS
      target: 50]). Perioperative analgesia was provided by high thoracic epidural
      analgesia (TEA group, bupivacaine 0.125%, 6 to 14 mL/h) or fentanyl, up to 10
      microg/kg, followed by patient-controlled analgesia with morphine (OPIOID group).
      MEASUREMENTS AND MAIN RESULTS: Success of extubation within 30 minutes after
      surgery was recorded. Hemodynamic data during surgery were compared by using an
      analysis of variance test; p < 0.05 was considered as showing a significant
      difference. Data presented as median (25th-75th percentile). In the TEA group,
      patients underwent simple aortic valve replacement (N = 21) or combined aortic
      valve surgery (N = 14), with additional coronary artery bypass grafting (N = 10)
      and replacement of the ascending aorta (Bentall, N = 4). In the OPIOID group,
      patients underwent simple aortic valve replacement (N = 5) or combined aortic
      valve surgery (N = 5), with additional aortocoronary bypass grafting (N = 2),
      replacement of the ascending aorta (Bentall, N = 2), and reconstruction of the
      mitral valve (N = 1). All 45 patients were extubated within 15 minutes after
      surgery. There was no need for reintubation; pain scores were lower in the TEA
      group than in the OPIOID group immediately after surgery and at 6 hours, 24
      hours, and 48 hours after surgery. For the TEA group and OPIOID group, the pain
      scores were 0 (0-2), 0 (0-2), 0 (0-1.5), and 0 (0-0) and 5 (4-5.75), 4 (3-4.5), 4
      (3.25-4), and 1 (0-2.5), respectively. During and up to 6 hours after surgery,
      there was no significant hemodynamic difference between the TEA and OPIOID
      groups. Eighteen of 45 patients needed temporary pacemaker activation. There were
      no epidural hematoma or neurologic complications related to TEA. CONCLUSION:
      Immediate extubation is feasible after aortic valve surgery using either high
      thoracic epidural analgesia or opioid-based analgesia; both techniques maintain
      hemodynamic stability throughout surgery. TEA provides superior pain control.

PMID- 15868525
TI  - Atrial fibrillation in elderly patients after cardiac surgery: postoperative
      hemodynamics and low postoperative serum triiodothyronine.
AB  - OBJECTIVE: The purpose of this study was to evaluate serum triiodothyronine
      levels as a trigger of postoperative atrial fibrillation (AF) in elderly patients
      undergoing cardiac surgery and to study the possible association of serum
      triiodothyronine levels with preoperative and postoperative hemodynamics. DESIGN:
      Prospective study. SETTING: University hospital. PARTICIPANTS: Forty-six
      consecutive nonemergency patients 65 years or older undergoing cardiac surgery
      during 1999 to 2000 in Tampere University Hospital, Tampere, Finland.
      INTERVENTIONS: Free serum T3 concentration was used as a measure of serum
      triiodothyronine levels. Samples were taken preoperatively, on the fourth
      postoperative day, and at the 3-month follow-up. The hemodynamic state of the
      patients was estimated by whole-body impedance cardiography preoperatively,
      during the intensive care unit period, daily until the fourth postoperative day,
      and at the 3-month follow-up. MEASUREMENTS AND MAIN RESULTS: AF occurred in 43%
      of the patients. The patients in the AF group had significantly more grafts (3.9
      v 3.1, p = 0.02), and there was a small difference in age between the AF and non
      AF groups (73 years v 69 years, p = 0.06). The free T3 concentration on the
      fourth postoperative day was significantly lower in the AF group (3.5 nmol/L v
      4.6 nmol/L, p = 0.04). In logistic regression analysis, the independent
      predictors of AF were age, number of grafts, and serum free T3 concentration on
      the fourth postoperative day. In the group with low T3 concentration, the cardiac
      index was lower (1.4 v 1.8, p = 0.05) and the systemic vascular resistance index
      was higher (4,064 v 2,969, p = 0.04) but only immediately after the operation.
      Although the AF mostly appeared during the second to fourth postoperative days,
      there were no longer any differences in the hemodynamic state at that time.
      CONCLUSIONS: In a group of elderly patients undergoing cardiac surgery, there was
      a strong association between a postoperative decrease of serum triiodothyronine
      levels and atrial fibrillation. The decrease of serum triiodothyronine levels was
      related to the changes of hemodynamic parameters only in the immediate
      postoperative period.

PMID- 15868526
TI  - Pulmonary and renal function following cardiopulmonary bypass is associated with
      systemic capillary leak.
AB  - OBJECTIVE: The purpose of this study was to compare perioperative capillary
      permeability during cardiac surgery with subsequent pulmonary and renal function.
      DESIGN: An observational prospective comparison of capillary permeability
      (microalbuminuria) during and after cardiopulmonary bypass (CPB), with
      postoperative pulmonary and renal function. SETTING: A university teaching
      hospital. PARTICIPANTS: Forty patients, mean (range) age 67.8 (50-85) years,
      undergoing elective first-time coronary artery bypass grafting (CABG).
      INTERVENTIONS: Urine albumin concentration (AC) and albumin creatinine ratio
      (ACR) were compared with PO2 /FIO2 ratio, mechanical ventilation (intermittent
      positive-pressure ventilation [IPPV]) duration, and renal function. MEASUREMENTS
      AND MAIN RESULTS: Median (range) AC and ACR increased from 8.3 (1.6-184.2) mg/L
      and 0.65 (0.1-18.8) mg/mmol preoperatively to 13.6 (1.6-267.2) mg/L and 4.80 (0.3
      54.2) mg/mmol 10 minutes postbypass (p = 0.003 for ACR Wilcoxon rank test: not
      significant for AC). AC 2 hours postbypass was associated with mean PO2 /FIO2
      ratio 0 to 2 hours postbypass and AC 4 hours postbypass was associated with mean
      PO2 /FIO2 ratio 0 to 2 and 2 to 12 hours postbypass (p < 0.05 Spearman). ACR 2
      hours postbypass was associated with mean PO2 /FIO2 ratio 0 to 2 and 2 to 12
      hours postbypass (p < 0.05 Spearman). AC 10 minutes and 2 hours postbypass and
      ACR 2 hours postbypass were associated with the duration of IPPV (p < 0.03). Day
      1 serum creatinine was associated with pre- and 4 hours postbypass AC and ACR (p
      < 0.05). Day 2 serum creatinine was associated with 2 and 4 hours postbypass ACR
      (p < 0.05). CONCLUSIONS: The magnitude of increase in capillary permeability
      during CABG is associated with later pulmonary and renal function.

PMID- 15868527
TI  - Off-pump coronary artery bypass grafting reduces postoperative neurologic
      complications.
AB  - OBJECTIVE: Complications occurring after coronary artery bypass graft (CABG)
      surgery, particularly neurologic damage, have been mainly correlated with the use
      of cardiopulmonary bypass (CPB). The aim of this work was to compare
      postoperative outcomes of patients undergoing CABG surgery, with or without the
      use of CPB, focusing on neurologic events. DESIGN: Observational study. SETTING:
      University tertiary care hospital. PARTICIPANTS: Two thousand seven hundred and
      forty consecutive patients who underwent CABG surgery in the period January 1998
      to January 2003. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For 738
      patients, the operation was performed off-pump (OP group), and for 2002 patients
      CPB was used (CPB group). OP and CPB groups were compared with regard to
      preoperative status, anesthetic management, and postoperative outcomes, by means
      of univariate and multivariate analyses. Surgeons' propensity to operate off-pump
      was based on patients' age, renal conditions, and hemodynamics. Univariate and
      multivariate analyses showed that CPB was associated with a higher incidence of
      type I neurologic events compared with OP technique (2.1% versus 0.9%, odds ratio
      [OR]: 2.6, 95% confidence interval [CI], 1.2-5.9). A history of previous stroke
      (OR: 2.7, 95% CI, 1.2-5.9) and advanced age (OR: 1.06 per year, 95% CI, 1.02
      1.09) were additional independent predictors of postoperative type I neurologic
      events. CONCLUSIONS: In the authors' experience, off-pump CABG surgery offers
      some benefits compared with CPB in respect to major neurologic complications.

PMID- 15868528
TI  - The mechanisms of the direct vascular effects of fentanyl on isolated human
      saphenous veins in vitro.
AB  - OBJECTIVE: The purpose of this study was to determine the mechanism of the direct
      effects of fentanyl on human veins in vitro. DESIGN: In vitro, prospective with
      repeated measures. SETTING: University research laboratory. INTERVENTIONS: Dose
      response curves were obtained for cumulative doses of fentanyl (10(-9)-10(-5)
      mol/L) on saphenous vein strips precontracted with (10(-6) mol/L) 5
      hydroxytryptamine incubated with either naloxone (10(-4) mol/L), Nomega-nitroL
      arginine-methyl ester (L-NAME) (10(-4) mol/L), indomethacin (10(-5) mol/L),
      glibenclamide (10(-4) mol/L), tetraethylammonium (10(-4) mol/L), or ouabain (10(
      5) mol/L). Vein strips were also exposed to a Ca++-free solution and 0.1 mmol/L
      of ethylene glycol-bis-(b-aminoethylether) N,N'-tetraacetic acid; 5
      hydroxytryptamine (10(-6) mol/L) was added to the bath before cumulative Ca++
      (10(-4)-10(-2) mol/L). The same procedure was repeated in the presence of
      fentanyl (10(-6) , 3 x 10(-6) , or 10(-5) mol/L) (p < 0.05 = significant).
      MEASUREMENTS AND MAIN RESULTS: Preincubation of vein strips with naloxone, L
      NAME, or indomethacin did not influence the relaxant responses to fentanyl (p >
      0.05). Tetraethylammonium, glibenclamide, and ouabain reduced the relaxation
      response to fentanyl (p < 0.05). A stepwise increase in tension was recorded with
      cumulative doses of Ca++ (p < 0.05). CONCLUSIONS: The present results show that
      fentanyl causes vasodilatation via both endothelium- and opioid receptor
      independent mechanisms in the human saphenous vein. The relaxant effects of
      fentanyl are probably via activation of K+ channel and Na+K+-adenosine
      trisphosphatase and inhibition of Ca++ channel.

PMID- 15868530
TI  - Intraoperative esophageal dilation for TEE probe placement in a patient with an
      undiagnosed esophageal stricture.

PMID- 15868529
TI  - Intraoperative glucose control in diabetic and nondiabetic patients during
      cardiac surgery.
AB  - OBJECTIVE: The purpose of this study was to evaluate intraoperative glucose
      control. DESIGN: Prospective unblinded study. SETTING: Tertiary care center.
      PARTICIPANTS: Diabetic (n = 17) and nondiabetic (n = 23) patients undergoing
      elective cardiac surgery. INTERVENTIONS: Diabetics received a modified insulin
      regimen consisting of a fixed rate infusion of regular insulin, 10 U/m2/h, and a
      variable infusion of D10W, adjusted to maintain glucose between 101 to 140 mg/dL.
      MEASUREMENTS AND MAIN RESULTS: Baseline glucose was higher in diabetics versus
      nondiabetics (mean +/- standard error of the mean: 203 +/- 27 v 117 +/- 3 mg/dL,
      p < 0.005). After baseline, insulin levels were increased in diabetics to 410 to
      568 microU/mL. Corresponding insulin levels in nondiabetics were 12 to 40
      microU/mL. Compared with baseline, glucose was decreased by 10% +/- 29% in
      diabetics during hypothermic cardiopulmonary bypass and increased by 21% +/- 30%
      in nondiabetics (p < 0.005). After discontinuation of bypass, glucose was lower
      in diabetics (137 +/- 12 mg/dL) versus nondiabetics (162 +/- 8 mg/dL, p < 0.005).
      Nine diabetics had adequate intraoperative glycemic control during hypothermic
      bypass (glucose 123 +/- 8 mg/dL, insulin 550 +/- 68 microU/mL, glucose infusion
      rate 1.87 +/- 0.29 mg/kg/min), 6 approached adequate control near the end of
      surgery (glucose 147 +/- 8 mg/dL, insulin 483 +/- 86 microU/mL, glucose infusion
      rate 0.35 +/- 0.05 mg/kg/min), and 2 never achieved control. Diabetics with
      elevated initial glucose >300 mg/dL did not achieve adequate glycemic control.
      Four diabetics (3 with renal failure) required injection of 50% dextrose after
      bypass for hypoglycemia. CONCLUSION: Adequate glycemic control can be achieved in
      most diabetics during cardiac surgery using a modified insulin clamp technique
      provided initial glucose is <300 mg/dL.

PMID- 15868531
TI  - Anesthetic management of neonates with congenital complete atrioventricular heart
      block undergoing pacemaker implantation.

PMID- 15868532
TI  - Closed-eye visual hallucinations after coronary artery bypass grafting.

PMID- 15868533
TI  - Combined sciatic and femoral nerve blocks for infrainguinal arterial bypass
      surgery: a case series.

PMID- 15868534
TI  - Management of thrombectomy for acute thrombosis of aortic composite valve graft
      in pregnancy.

PMID- 15868535
TI  - Pulmonary vein thrombosis after sequential double-lung transplantation.

PMID- 15868536
TI  - Diastolic dysfunction in the older heart.

PMID- 15868537
TI  - Perioperative beta-blockade and late cardiac outcomes: a complementary
      hypothesis.

PMID- 15868538
TI  - Case 2-2005: evaluation of the lungs via transesophageal echocardiography.

PMID- 15868539
TI  - Pro: Steroids should be used for cardiopulmonary bypass.

PMID- 15868540
TI  - Con: Methylprednisolone is not indicated for patients during cardiopulmonary
      bypass.

PMID- 15868541
TI  - A rare complication of intra-aortic balloon pump placement.

PMID- 15868542
TI  - What is in the chest?

PMID- 15868545
TI  - Improved oxygenation during one-lung ventilation achieved with an embolectomy
      catheter acting as a selective lobar endobronchial blocker.

PMID- 15868546
TI  - Detachment of Arndt endobronchial balloon cuff into right mainstem bronchus.

PMID- 15868547
TI  - Combination of phenoxybenzamine and nitroglycerin: effective control of pulmonary
      artery pressures in children undergoing cardiac surgery.

PMID- 15868548
TI  - The use of bispectral index for diagnosis of aortic arch arterial occlusion.

PMID- 15868549
TI  - Managing severe mitral valve stenosis in pregnant patients--percutaneous balloon
      valvuloplasty, not surgery, is the treatment of choice.

PMID- 15868551
TI  - We've come a long way: it's finally time to get started!

PMID- 15868552
TI  - Tomorrow's surgeon--who cares for the patient? The impact of the European working
      time directive.

PMID- 15868553
TI  - Intratracheal pulmonary ventilation improves gas exchange during laparoscopy in a
      pediatric lung injury model.
AB  - BACKGROUND/PURPOSE: This study was aimed at determining whether intraoperative
      intratracheal pulmonary ventilation (ITPV) could prevent/treat respiratory
      complications of laparoscopy in a model of pediatric pulmonary insufficiency.
      METHODS: Severe lung injury was induced in 0- to 2-month-old lambs (n = 5) by
      endotracheal saline lavage. Animals then underwent establishment of CO2
      pneumoperitoneum. Intraperitoneal pressures were progressively raised from 0 to
      15 mm Hg, at intervals of 5 mm Hg. At each interval, blood gas and hemodynamic
      data were recorded, 20 minutes after initiation of both conventional ventilation
      and pure ITPV. All ventilatory parameters were constant and identical on both
      modes of ventilation. RESULTS: On conventional ventilation, severe respiratory
      acidosis and hypoxemia ensued at intraperitoneal pressures of 5 mm Hg and 10 mm
      Hg or more, respectively. Compared with conventional ventilation, ITPV led to
      statistically significant decreases in PCO2 at intraperitoneal pressures of 5 mm
      Hg (43.2 +/- 5.2 vs 56.1 +/- 6.6 mm Hg) and 10 mm Hg (45.1 +/- 3.2 vs 61 +/- 6.3
      mm Hg) and to significant increases in PO2 at 10 mm Hg (92 +/- 10.2 vs 61 +/- 8.1
      mm Hg), resolving the acidosis and hypoxemia at those pressure levels.
      CONCLUSIONS: Compared with conventional ventilation, ITPV improves both CO2
      removal and oxygenation during CO2 pneumoperitoneum in a pediatric lung injury
      model. Intratracheal pulmonary ventilation may be a safer intraoperative mode of
      ventilation for neonates and children with respiratory failure who require
      laparoscopy.

PMID- 15868554
TI  - Postnatal lung mechanics, lung composition, and surfactant synthesis after
      tracheal occlusion vs prenatal intrapulmonary instillation of perfluorocarbon in
      fetal rabbits.
AB  - BACKGROUND/PURPOSE: Fetal tracheal occlusion (TO) accelerates lung growth but
      decreases surfactant production. We have previously shown that instillation of
      perfluorooctylbromide (PFOB) into fetal rabbit lungs leads to lung growth similar
      to TO. This study compares neonatal lung mechanics and surfactant production
      after prenatal intrapulmonary PFOB instillation vs TO. METHODS: In each of 18
      pregnant rabbits on gestational day 27, sets of 4 fetuses underwent either (1)
      intrapulmonary instillation of 1 mL PFOB, (2) TO, (3) instillation of 1 mL 0.9%
      NaCl (saline), and (4) hysteroamniotomy without fetal manipulation (control).
      Fetuses were born by cesarean delivery after 48 hours. Fetuses of 12 rabbits were
      mechanically ventilated for 15 minutes to evaluate lung compliance and airway
      resistance. Pulmonary surfactant protein B (SP-B) was quantified by
      immunohistochemistry in fetuses of the remaining 6 rabbits. RESULTS: Compliance
      was decreased in the TO group after cesarean delivery (0.33 +/- 0.13 mL/cm H2O)
      compared with PFOB (0.59 +/- 0.12 mL/cm H2O), saline (0.50 +/- 0.12 mL/cm H2O),
      and control (0.52 +/- 0.10 mL/cm H2O) fetuses. Mean fetal lung to body weight
      ratio was higher in TO and PFOB fetuses compared with saline and control. Higher
      water content and lower numbers of surfactant protein B-positive cells were found
      in the TO-treated fetuses. CONCLUSIONS: Both prenatal intrapulmonary instillation
      of PFOB and TO accelerate lung growth, but TO is associated with decreased
      postnatal lung compliance, possibly influenced by decreased surfactant production
      and increased fluid retention. Conversely, instillation of PFOB preserved lung
      compliance and surfactant synthesis.

PMID- 15868555
TI  - The role of oxygen tension in the regulation of embryonic lung development.
AB  - BACKGROUND/PURPOSE: Oxygen tension is an important physiologic mediator of
      embryonic and fetal development. In vitro studies have demonstrated that the
      proper embryonic development is dependent upon low oxygen tension and even short
      exposure to normoxic environments (21%) can be detrimental to embryonic
      development. We hypothesized that low oxygen tension promotes lung growth in
      embryonic organ culture and therefore designed this study to investigate
      embryonic lung growth in normoxic and hypoxic conditions using simple closed
      chamber. METHODS: Fetal rat lungs were harvested on day 13.5 and placed in organ
      culture containing serum-free Dulbecco's modified Eagle's medium with
      antibiotics. The lung cultures were divided into normoxic group, with a 21%
      oxygen concentration (n = 15), and hypoxic group (n = 15). Hypoxic condition (6%
      oxygen) was achieved using Oxoid Campygen in a closed chamber. The lungs were
      placed in 5% carbon dioxide, 37 degrees C incubator for 48 hours. Media were not
      changed during the incubation period. The morphometric analysis was measured at 0
      hour and at 48 hours by counting total terminal buds and entire epithelial
      contour using Image J software. The fold increase in branching was calculated as
      the ratio of buds present at 48 hours minus the buds present at 0 hour divided by
      the number of buds at 0 hour. The increase in entire epithelial contour over 48
      hours was calculated in exactly the same way as described above. RESULTS: There
      was no significant difference in the increase in total terminal buds count in the
      hypoxic group (2.06 +/- 0.19) compared with the normoxic group (2.59 +/- 0.21),
      and no significant difference in the increase in entire epithelial contour in the
      hypoxic group (1.45 +/- 0.11) compared with the normoxic group (1.63 +/- 0.11).
      CONCLUSIONS: Although hypoxia has been reported to be an important regulator of
      murine vascular development, our data show that the embryonic lung growth in
      whole lung organ culture under hypoxic condition is not significantly different
      from that in normoxic condition.

PMID- 15868556
TI  - Survival of severe congenital diaphragmatic hernia has morbid consequences.
AB  - BACKGROUND/PURPOSE: Fetal tracheal occlusion (TO) was developed in an attempt to
      enhance prenatal lung growth and improve survival in fetuses with severe
      congenital diaphragmatic hernia (CDH). We conducted a randomized, controlled
      clinical trial in 24 fetuses with severe left CDH (liver herniated into the
      thorax and low lung-to-head ratio) to compare survival after endoscopic fetal TO
      vs standard perinatal care (control) and prospectively followed up the 16
      survivors (9 control, 7 TO) to compare neurodevelopmental, respiratory, surgical,
      growth, and nutritional outcomes. METHODS: At 1 and 2 years old, subjects
      underwent evaluation consisting of medical and neurological history and physical,
      developmental testing, nutritional assessment, oxygen saturation and pulmonary
      function testing, chest radiograph, and echocardiogram. Growth and developmental
      measures were corrected for prematurity. Data were analyzed by Mann-Whitney rank
      sum test, Fisher's Exact test, and logistic and linear regression. RESULTS:
      Infants with TO were significantly more premature at birth (control vs TO, 37.4
      +/- 1.0 vs 31.1 +/- 1.7 weeks; P < .01). Growth failure ( z score for weight <2
      SDs below mean) was severe in both groups at 1 year of age (control vs TO, 56% vs
      86%; P = .31). There was considerable catch-up growth by age 2 years (growth
      failure: control vs TO, 22% vs 33%; P = .19). There were no differences in other
      growth parameters. There were also no differences in neurodevelopmental outcome
      at 1 and 2 years. Supplemental oxygen at hospital discharge was a significant
      predictor of worse neurodevelopmental outcome at 1 and 2 years old (P = .05 and P
      = .02, respectively). Hearing loss requiring amplification has been diagnosed in
      44% of the group (control vs TO, 44% vs 43%; P = 1.0). CONCLUSIONS: In this group
      of infants with severe CDH, there were no differences in outcome at 2 years old
      despite significant prematurity in the TO group. Oxygen supplementation at
      hospital discharge identified the most vulnerable group with respect to
      neurodevelopmental outcome, but all infants had significant growth failure, and
      hearing impairment is a substantial problem in this population. Severe CDH
      carries significant risk of chronic morbidity.

PMID- 15868557
TI  - Differences in the outcome of surgically placed long-term central venous
      catheters in neonates: neck vs groin placement.
AB  - BACKGROUND/PURPOSE: Long-term tunneled central venous catheters (CVC) are
      frequently used in the neonatal intensive care unit (NICU) babies. They are
      placed either in the neck or groin based primarily upon the surgeon's preference.
      There is meager published information available about the relative risks of these
      lines. METHODS: This is a retrospective analysis of all the tunneled central
      venous catheters placed in NICU babies at a children's hospital over a nearly 5
      year period. Single lumen Broviac catheters were used in all cases. RESULTS: A
      total of 137 catheters were placed in 126 patients. There were 88 neck lines and
      49 groin lines. Age, gestational maturity, and body weight were significantly
      lower for babies who underwent groin line placement. There was no significant
      difference in the number of days the catheters were live between the 2 groups.
      Total complication rates and catheter infection rates were significantly higher
      with neck lines. The accidental removal rate was higher with neck lines but did
      not reach statistical significance. CONCLUSIONS: Broviac catheters placed in the
      groin of NICU babies are associated with significantly fewer complications
      compared with those placed in the neck.

PMID- 15868558
TI  - Assessment of cysteine synthesis in very low-birth weight neonates using a
      [13C6]glucose tracer.
AB  - BACKGROUND/PURPOSE: Cysteine is an amino acid necessary for the synthesis of all
      proteins, the antioxidant glutathione, and the neuromodulator taurine. Whether
      cysteine is an essential amino acid for premature neonates remains controversial.
      Using a [13C6]glucose precursor in very-low-birth weight (VLBW) premature
      neonates, we measured the 13C content of cysteine in hepatically derived
      apolipoprotein (apo) B-100 and in the plasma to determine whether cysteine
      synthesis occurs and to relate minimum synthetic capacity to neonatal maturity.
      METHODS: Twelve VLBW premature neonates (birth weight, 907 +/- 274 [SD] g;
      gestational age, 26.8 +/- 2.4 weeks) were studied on day of life 7.8 +/- 4.2
      while on total parenteral nutrition (TPN) for 5.6 +/- 4.5 days. A 4-hour
      intravenous infusion of [13C6]glucose was administered. Blood samples were
      obtained immediately before and at the end of the infusion. Isotopic enrichment
      of cysteine was determined by gas chromatography/mass spectrometry. Analysis of
      variance, Student's t test, and linear regression were used for comparisons.
      RESULTS: The 13C isotope ratio of apo B-100-derived cysteine after the
      [13C6]glucose infusion was significantly higher than baseline (18.57 +/- 0.38
      [SEM] vs 17.54 +/- 0.25 mol%, P < .05). The 13C isotope ratio of plasma cysteine
      was also significantly higher than baseline (17.36 +/- 0.25 vs 16.91 +/- 0.16
      mol%, P < .05). When expressed as a product/precursor ratio, the mole percent
      above baseline of [13C]apo B-100 cysteine/[13C6]glucose correlated with birth
      weight (r = 0.74, P < .01). CONCLUSIONS: Very low-birth weight neonates are
      capable of cysteine synthesis as evidenced by incorporation of 13C label into
      hepatically derived apo B-100 cysteine and plasma cysteine from a glucose
      precursor. The minimum capacity for intrahepatic cysteine synthesis appears to be
      directly proportional to the maturity of the neonate and may impact the
      capabilities of VLBW neonates to counteract oxidative stresses such as
      bronchopulmonary dysplasia and necrotizing enterocolitis.

PMID- 15868559
TI  - The impact of hospitalwide computerized physician order entry on medical errors
      in a pediatric hospital.
AB  - PURPOSE: Medication errors contribute significantly to the morbidity and costs of
      pediatric health care. The authors hypothesized that hospitalwide computerized
      physician order entry (CPOE) in a pediatric hospital would lead to a decrease in
      medication errors. METHODS: The authors retrospectively evaluated and
      prospectively analyzed inpatient discharge and usage and adverse drug event (ADE)
      rate data pre- and postintroduction of a hospitalwide implementation of CPOE in a
      tertiary care pediatric hospital. They compared pre- and postintervention ADEs
      (Student's t test) and computed the number needed to treat (NNT) analog. RESULTS:
      Over the 9-month study period, there were 45,615 in patient days and 8619
      discharges. Pre-CPOE verbal order regulatory compliance was 80%, whereas post
      CPOE increased to 95%. Transcription errors were eliminated. All ADEs pre-CPOE
      were 0.3 +/- 0.04 per 1000 doses, whereas post-CPOE ADEs were 0.37 +/- 0.05 per
      1000 doses (P = .3). Harmful ADEs pre-CPOE were 0.05 +/- 0.017 per 1000 doses,
      while post-CPOE ADEs were 0.03 +/- 0.003 per 1000 doses (P = .05). Our NNT data
      demonstrate that CPOE would prevent 1 ADE every 64 (95% CI 25-100) patient days.
      CONCLUSIONS: CPOE decreases harmful ADEs in a pediatric hospital, thus leading to
      increased patient safety. In addition, CPOE provides an automated system for
      monitoring and improving health care quality.

PMID- 15868560
TI  - The impact of the 80-hour workweek on pediatric surgical training: an Association
      of Pediatric Surgery Program Directors-sponsored study.
AB  - BACKGROUND/PURPOSE: The aim of this study was to determine the preliminary impact
      of work hour regulations on pediatric surgical training. METHODS: An anonymous
      survey was sent to all program directors (PDs) and fellows to identify changes in
      pediatric surgery fellowship programs. RESULTS: Ninety-three percent of programs
      and 87% of PDs responded. Thirty programs hired additional personnel, including
      nurse practitioners, physician assistants, and fellows outside the training
      program. Thirteen programs reported increased attending coverage. The daily
      composition of the surgical team has changed, with postcall fellows and residents
      leaving in the morning. Residents and fellows also take call less frequently.
      More than 50% of PDs felt that quality of care had declined and three quarters of
      respondents felt that continuity of care was worse. Half of the respondents
      feared missed educational opportunities. However, half of the fellows felt more
      rested, 61% reported more family time, and 22% reported increased social time. In
      contrast, no PDs perceived life-style improvements. CONCLUSIONS: The work hour
      regulations have resulted in fundamental changes in pediatric surgical training.
      Ongoing assessment is needed to prioritize quality of care, improve continuity of
      care, and track changes in operative, clinical, and didactic experiences of the
      trainees. The added impact of these changes on the time spent available for
      commitment to teaching by the faculty should be assessed.

PMID- 15868561
TI  - Cost considerations and applicant characteristics for the Pediatric Surgery
      Match.
AB  - BACKGROUND/PURPOSE: Formal training in pediatric surgery is highly competitive.
      The limited number of accredited positions has historically favored applicants
      with basic science experience, numerous publications, national presentations, and
      exposure to well-known pediatric surgeons. This review analyzes characteristics
      of successful applicants and cost associated with the Match. METHODS: A survey
      was e-mailed to 45 applicants after the 2003 Match. Geographic provenance,
      demographics, qualifications, costs, and valued program characteristics were
      assessed. Statistics were formulated by chi2 and Student's t test. RESULTS:
      Thirty-six applicants (80%) responded. Successful characteristics for matched vs
      unmatched included number of publications, 11.2 vs 5.7 (P < .01); first-author
      designation, 6.4 vs 3.1 (P = .02); basic science papers, 5.7 vs 1.7 (P < .01);
      national presentations, 5.8 vs 2.4 (P = .02); and presentations at pediatric
      surgical meetings, 2.0 vs 0.6 (P = .04). Ninety percent of matched applicants
      took time off to perform basic science research (P < .01). Average candidate
      expense was $6974, which represented 14% of pretax salary. Forty-one percent of
      applicants noted that cost limited the number of interviews taken. Fifty percent
      preferred a regional interview process to limit expense. Candidates ranked case
      diversity, volume, and mentor's advice as the most valued program
      characteristics. Successful applicants matched at their fifth rank on average.
      Eighty-six percent of unsuccessful applicants will reapply. CONCLUSIONS: Results
      of this study are important to those interested in the future of pediatric
      surgery. Successful applicants were shown to have several national presentations
      and multiple scientific publications, especially in basic sciences. Applicant
      costs are high, totaling more than $236,000 for survey respondents.

PMID- 15868562
TI  - Effect of subspecialty training and volume on outcome after pediatric inguinal
      hernia repair.
AB  - BACKGROUND/PURPOSE: Inguinal hernia repair is the most common operation performed
      in children. The aim of this study was to determine if there are any differences
      in outcome when this procedure is performed by subspecialist pediatric surgeons
      when compared with general surgeons. METHODS: All pediatric inguinal hernias
      repaired in the province of Ontario between 1993 and 2000 were reviewed using a
      population-based database. Children with complex medical conditions or
      prematurity were excluded. Cases done by general surgeons were compared with
      those done by pediatric surgeons. The chi2 test was used for nominal data and the
      Student's t test was used for continuous variables. Probabilities were calculated
      based on a logistic regression model. RESULTS: Of 20,545 eligible hernia repairs,
      50.3% were performed by pediatric surgeons and 49.7% were performed by general
      surgeons. Pediatric surgeons operated on 62.4% of children younger than 2 years,
      51.8% of children aged 26 years, and 37% of children older than 7 years. Duration
      of operation, length of hospital stay, and incidence of early postoperative
      complications were similar among pediatric and general surgeons. The rate of
      recurrent inguinal hernia was higher in the general surgeon group compared with
      pediatric surgeons (1.10% vs 0.45%, P < .001). Among pediatric surgeons, the
      estimated risk of hernia recurrence was independent of surgical volume. There was
      a significant inverse correlation between surgeon volume and recurrence risk
      among general surgeons, with the highest volume general surgeons achieving
      recurrence rates similar to pediatric surgeons. CONCLUSIONS: Pediatric surgeons
      have a lower rate of recurrence after inguinal hernia repair in children. General
      surgeons with high volumes have similar outcomes to pediatric surgeons.

PMID- 15868563
TI  - Development of a parathyroid hormone-controlled release system as a potential
      surgical treatment for hypoparathyroidism.
AB  - BACKGROUND/PURPOSE: The aim of this study was to develop a surgically implantable
      controlled release delivery system for parathyroid hormone (PTH) that will
      maintain calcium homeostasis without the adverse side effects of long-term
      calcium and vitamin D replacement and can be used for the treatment of
      hypoparathyroidism. METHODS: Biodegradable poly(lactide-co-glycolide) (PLGA)
      microspheres loaded with PTH were made using a modification of the double
      emulsion (water/oil/water) solvent evaporation technique. To simulate the release
      of PTH from microspheres after implantation in an animal, the in vitro release
      profile for the PTH microspheres was determined by incubating the PTH
      microspheres in phosphate-buffered saline, serially sampling the effluent, and
      determining the concentration of PTH in the effluent over time using an enzyme
      linked immunosorbent assay. RESULTS: (1) PTH was successfully incorporated into
      PLGA microspheres. (2) Controlled release of PTH was demonstrated in vitro over a
      3-week period. (3) Release of physiological significant concentrations of PTH was
      achieved using this methodology. CONCLUSIONS: Controlled release of physiological
      concentrations of PTH can be achieved using PLGA microsphere encapsulation.

PMID- 15868564
TI  - Laparoscopic adjustable gastric banding for the treatment of adolescent morbid
      obesity in the United States: a safe alternative to gastric bypass.
AB  - BACKGROUND: Morbid obesity (MO) has reached epidemic proportions and is a major
      health problem in developed nations. In the adolescent with MO, early
      intervention can minimize obesity-related comorbidities, avoid premature
      mortality, improve quality of life, and prevent obesity-related diseases as these
      patients mature into adulthood. The primary surgical treatment of adolescent
      patients meeting National Institutes of Health criteria for bariatric surgery has
      been the gastric bypass (GB). Although GB has led to weight loss and improvement
      of comorbid conditions, concerns remain over the high incidence of postoperative
      complications and life-style-altering long-term sequelae of gastrointestinal
      tract reconstruction. Based on the excellent results from international adult
      series as well as the authors' own experience of more than 300 adult patients,
      laparoscopic adjustable gastric banding (LAGB) as an alternative to GB to
      eligible adolescents was offered. METHODS: After medical, psychologic, and
      nutritional screening, 4 patients (ages 17-19 years) with a body mass index of 40
      or more (range, 40-61) who failed medical attempts at weight loss were selected
      for LAGB. RESULTS: The operative time was 40 to 90 minutes. All patients were
      discharged on the day of surgery. There were no early complications. One patient
      had cholecystitis 6 months after surgery requiring laparoscopic cholecystectomy.
      For the 4 patients, the amount of excess weight loss was 57% at 30 months, 34% at
      12 months, 87% at 7 months, and 15% at 4 months, respectively. CONCLUSIONS: In
      this preliminary series of the US experience in the use of LAGB for the
      management of adolescents with MO, the lack of operative morbidity, short
      operative time/hospital stay, and encouraging initial weight loss mirror the
      adult experience and illustrate that the LAGB is a safe and effective alternative
      to GB. These encouraging results support further evaluation of LAGB as a surgical
      option in a comprehensive adolescent weight loss program.

PMID- 15868565
TI  - Epidermal growth factor receptor signaling regulates goblet cell production after
      small bowel resection.
AB  - BACKGROUND/PURPOSE: Intestinal adaptation is a compensatory response to massive
      small bowel loss in which there are increased numbers of absorptive enterocytes.
      However, the generation of secretory epithelial cell subtypes in this process has
      not been investigated. The purpose of this study was to examine the adaptive
      changes of several small intestinal cell lineage changes in response to massive
      small bowel resection (SBR). METHODS: A 75% SBR or sham operation was performed
      on male Sprague-Dawley rats. On postoperative day 7, the remnant ileum was
      harvested and immunohistochemical staining for goblet, Paneth, and
      enteroendocrine cells was performed. Cell subtypes were evaluated as cells per
      micrometer of villus/crypt length and compared among operations. RESULTS: A
      significant increase in goblet cell density occurred after SBR. Intestinal
      resection did not alter the number of Paneth and enteroendocrine cells. In
      additional experiments, inhibition of epidermal growth factor receptor signaling
      was associated with a diminished goblet cell density. CONCLUSIONS: The adaptive
      response of the intestine to massive bowel loss results in an expansion of the
      goblet cell population in addition to greater numbers of absorptive enterocytes.
      Although the mechanism and purpose for selective expansion of these stem cell
      derived lineages are not presently known, epidermal growth factor receptor
      signaling appears to be a common pathway.

PMID- 15868566
TI  - Risk factors for blunt thoracic aortic injury in children.
AB  - BACKGROUND/PURPOSE: Because blunt thoracic aortic injury is rare in children, a
      high index of suspicion is needed to identify this injury. The purpose of this
      study was to use a large national trauma database to define the risk factors for
      blunt thoracic aortic injury in children. METHODS: Using the National Trauma
      Database, the authors compared patient demographics, mechanism of injury, and
      associated injuries between children sustaining blunt trauma with and without a
      thoracic aortic injury. Factors independently associated with this injury were
      identified using multivariate methods. RESULTS: Among 26,940 children with a
      blunt mechanism of injury, 34 (0.1%) children sustained a thoracic aortic injury,
      14 (41%) of whom died. Thoracic aortic injuries were independently associated
      with age, injury sustained as an occupant in a motor vehicle crash, and severe
      injuries (Abbreviated Injury Scale value of > or =3) involving the head, thorax
      (other than aorta), abdomen, and lower extremities. CONCLUSIONS: Older children
      involved in a motor vehicle crash with severe head, torso, and lower extremity
      injuries are a group at high risk for injury to the thoracic aorta. These easily
      identifiable risk factors may facilitate more rapid identification of this rare
      and potentially fatal injury.

PMID- 15868567
TI  - Pediatric trauma patients with isolated airway compromise or Glasgow Coma Scale
      less than 8: does immediate attending surgeon's presence upon arrival make a
      difference?
AB  - BACKGROUND/PURPOSE: Optimal trauma care requires an attending pediatric surgeon
      to head a trauma team for the most severely injured patients. Recently, the
      American College of Surgeons-Committee on Trauma has added "Glasgow Coma Scale
      (GCS) <8" and "airway compromise" to the existing anatomical and physiological
      criteria for immediate attending presence. This report analyzes the outcome of
      children who met these isolated criteria and were treated before the change in
      guidelines was made. METHODS: The trauma registry of this level I trauma center
      was queried for all pediatric patients with GCS <8 or airway compromise. Age,
      sex, initial GCS, Revised Trauma Score, Injury Severity Score, outcome, and
      probability of survival (TRISS methodology) were recorded. The subgroup of
      patients for whom an attending surgeon was not immediately present was further
      analyzed. RESULTS: Over a 5-year period, 2895 trauma patients (aged 0-16 years)
      were admitted. One hundred fifteen patients had a GCS <8 and/or airway
      compromise. In 61 cases, an attending surgeon was not present upon patient
      arrival. Of these patients, 24 died (group D), 15 were discharged to a
      rehabilitation facility (group R), and 22 were discharged home (group H). Ten
      patients with a probability of survival of lower than 0.5 survived. Only 4 of the
      24 patients who died had a probability of survival of >0.5 (mean, 0.697). All 4
      had an Injury Severity Score >25 and a GCS < or =4. All deaths were reviewed
      through a quality improvement program and were deemed nonpreventable by objective
      reviewers. Patient outcome was not affected by the presence or absence of an
      attending surgeon upon patient arrival. CONCLUSIONS: Outcome of severely injured
      children with GCS <8 or airway compromise met and, in some cases, exceeded
      expectations of survival according to the TRISS methodology. The lack of
      immediate attending surgeon's presence does not appear to have negatively
      influenced the outcome in these children. Based on this series, there is no
      evidence to justify mandatory immediate presence of an attending surgeon for
      these 2 criteria alone.

PMID- 15868568
TI  - Pediatric pelvic injury: functional outcome at 6-month follow-up.
AB  - BACKGROUND/PURPOSE: Data on functional outcomes after pediatric pelvic fractures
      are limited to those obtained at hospital discharge. This study assesses
      functional status at both hospital discharge and at 6 months after injury.
      METHODS: A national multicenter prospective study began in February 2002 and is
      ongoing. Patients completed WeeFIM functional assessments at hospital discharge
      and at 6-month follow-up as part of this study. This report summarizes
      preliminary functional assessment results from 20 patients. RESULTS: Patient data
      were accrued into 3 domains (self-care, mobility, and cognition), which
      constitute a total raw rating. Significant improvement at 6 months after injury
      was evident in self-care, mobility, and total raw ratings. This significance
      remained when total raw ratings were converted to age-adjusted functional
      quotients. CONCLUSIONS: This preliminary assessment shows that after pelvic
      fractures, children improve their functional status at 6 months, returning to
      near-normal status.

PMID- 15868569
TI  - The multi-institutional validation of the new screening index for physical child
      abuse.
AB  - BACKGROUND/PURPOSE: There is currently no evidence-based screening instrument to
      assist in the detection of physical child abuse patients. The screening index for
      physical child abuse (SIPCA) was previously developed as a potentially new tool
      for this need. It is a scale that assigns point values, on the basis of variable
      weights from logistic regression models, to age and patterns of injuries
      (including fracture of base or vault of skull, contusion of eye, rib fracture,
      intracranial bleeding, multiple burns), with higher scores indicating greater
      suspicion for abuse. The purpose of this study is to validate this new tool in
      another independent data set. METHODS: A cross-sectional hospital discharge
      database from 1961 hospitals in 17 states is used (n = 58558). Children aged 14
      years or younger with International Classification of Diseases, Ninth Revision,
      Clinical Modification codes 800 to 959 are included for analysis. Child abuse
      cases are identified by E codes and certain International Classification of
      Diseases, Ninth Revision, Clinical Modification codes in the 995.5x range.
      Screening index for physical child abuse performance is evaluated by
      discrimination (receiver operating characteristic) and goodness of fit (pseudo
      r2). RESULTS: A total of 447 abused patients (0.76%) was identified. The receiver
      operating characteristic of SIPCA in this data set is 0.89 as compared with 0.86
      in the development data set. The pseudo r 2 of SIPCA in this data set is 0.26 as
      compared with 0.28 in the development data set. A SIPCA score of 3 has a
      sensitivity of 86.6% and a specificity of 80.5% for detecting physical abuse;
      raising the threshold to a score of 4 improves the specificity to 93.1% but at a
      loss of sensitivity to 71.8%. CONCLUSIONS: The validity of the new SIPCA
      instrument is supported by its performance in an independently derived data set.
      A score of 3 on SIPCA represents a balanced trade off in the sensitivity and
      specificity of the instrument in detecting physical abuse and is an optimal
      threshold above which to begin considering abuse in differential diagnosis.
      Application of the instrument could assist clinicians in detecting physical child
      abuse cases among pediatric trauma patients.

PMID- 15868570
TI  - The risk of child abuse in infants and toddlers with lower extremity injuries.
AB  - PURPOSE: The aim of this study was to assess the risk of child abuse in children
      younger than 18 months admitted to a pediatric trauma service with lower
      extremity injuries. METHODS: An Institutional Review Board-approved retrospective
      case series of children admitted to a regional pediatric trauma center with lower
      extremity injuries from 1998 to 2002 (n = 5497) was performed. Factors analyzed
      included age, injuries, and injury mechanism. RESULTS: Among 5497 trauma
      patients, the incidence of abuse was 104 (2%) of 4942 children 18 months or older
      and 175(32%) of 555 children younger than 18 months (odds ratio [OR], 21.4 +/-
      2.9, P < .001). There were 1252 (23%) patients with lower extremity injuries in
      the entire sample, and 66 of these were younger than 18 months. In the extremity
      trauma group, for patients 18 months or older, 16 (1%) of 1186 were abused
      compared with 44 (67%) of 66 patients younger than 18 months (OR, 146 +/- 53, P <
      .001). Among all trauma patients younger than 18 months, 41 of 55 lower extremity
      fractures were linked to abuse, whereas 134 of 500 other injuries were caused by
      abuse (OR, 8.0 +/- 2.6, P < .001). Among the 41 abuse-related fractures, femur
      fracture was the most common (22), followed by tibia fracture (14). CONCLUSIONS:
      Among children 18 months or older, abuse is an uncommon cause of lower extremity
      trauma. In children younger than 18 months, lower extremity injuries,
      particularly fractures, are highly associated with child abuse. Clinicians must
      thoroughly investigate lower extremity injuries in this age group.

PMID- 15868571
TI  - Pulmonary embolism: which pediatric trauma patients are at risk?
AB  - BACKGROUND/PURPOSE: Deep vein thrombosis and pulmonary embolism (DVT/PE) are rare
      in pediatric trauma patients, and guidelines for prophylaxis are scarce. The
      authors sought to identify subgroups of patients who may be at higher risk of
      developing DVT/PE. METHODS: Case-control study of pediatric trauma patients with
      DVT/PE. Odds ratios (ORs) and confidence intervals (CIs) were calculated for
      known risk factors of PE using matched trauma controls (chi2 analysis). RESULTS:
      A total of 3637 pediatric trauma patients was admitted over the last 7 years.
      Three patients developed DVT/PE (overall incidence, 0.08%). There were 2 girls
      and 1 boy, aged 15, 15, and 9 years, respectively. All 3 had an Injury Severity
      Score (ISS) > or =25 and an initial Glasgow Coma Score (GCS) < or =8. None of the
      known and potential risk factors significantly increased the OR for developing
      DVT/PE: age 9 years or older (OR, 3.6; CI, 0.4-26), presence of head injury (OR,
      2.9; CI, 0.3-22), female sex (OR, 1.2; CI, 0.15-9.1), GCS < or =8 (OR, 9.2; CI,
      0.9-230), except ISS > or =25 (OR, 82; CI, 7.6-2058). The OR for a combination of
      age and GCS was 106, and the OR for the 3 risk factors (age, ISS, GCS) common to
      all 3 patients was 114 (CI, 10-5000; P < .001). CONCLUSIONS: The overall
      incidence of DVT/PE in pediatric trauma patients is <0.1% and routine prophylaxis
      is not recommended. Children aged 9 years or older with an initial GCS < or =8
      and patients with an estimated ISS > or =25 may constitute a high-risk group in
      which prophylaxis could be considered.

PMID- 15868572
TI  - Wound management with vacuum-assisted closure: experience in 51 pediatric
      patients.
AB  - BACKGROUND/PURPOSE: Soft tissue loss from infectious, vascular, and traumatic
      disorders often results in poor healing, painful wound care, and the need for
      repeated operations. This retrospective study evaluates a single-institutional
      experience with negative pressure therapy (NPT), using the vacuum-assisted
      closure (VAC) device in a group of children with diverse soft tissue problems.
      METHODS: The medical records of 51 patients treated with NPT from January 2000 to
      July 2003 were reviewed for demographics, diagnosis, duration of VAC therapy,
      wound closure, recurrent disease, and complications. RESULTS: Patients were
      classified by diagnosis: group 1: pilonidal disease (n = 21, primary = 6 and
      recurrent = 15); group 2: sacral and extremity ulcers (n = 9); group 3: traumatic
      soft tissue wounds (n = 9); and group 4: extensive tissue loss (n = 12) from the
      abdominal wall (n = 7), perineum (n = 2), thigh (n = 2), and axilla (n = 1).
      Group 1 had an average age of 16 years (range, 10-20 years), 67% were obese, and
      had an average length of follow-up of 13 months (range, 8-36 months). VAC was
      placed in the operating room in 95% with subsequent outpatient care that included
      dressing change 3 times weekly. Healing occurred in all patients with primary
      disease at an average of 37 days. For patients with recurrent disease, 12 healed
      at an average of 48 days and 3 developed recurrent sinuses. Group 2 was treated
      with VAC as a bridge to skin grafting or flap closure. All children in group 3
      achieved healing without skin grafting at an average of 10 days and with
      acceptable cosmesis. Negative pressure therapy in group 4 was the only wound
      treatment in 10 patients and adjunctive to operative closure in 2. Complications
      from VAC occurred in 5 patients: retained sponge in 2 and device malfunction in
      3. CONCLUSIONS: Negative pressure therapy offers a safe, cost-effective
      alternative to traditional complex wound care in children. Its advantages are
      less frequent dressing changes, outpatient management, resumption of daily
      activities including return to school, and a high degree of patient tolerance.

PMID- 15868573
TI  - The incidence of complete androgen insensitivity in girls with inguinal hernias
      and assessment of screening by vaginal length measurement.
AB  - BACKGROUND/PURPOSE: Complete androgen insensitivity syndrome (CAIS) is a rare
      disorder; however, surgeons have noted a higher rate in girls with inguinal
      hernias. A few retrospective studies have estimated the incidence of CAIS to be
      0.8% to 2.4% in girls with inguinal hernias. An inexpensive, quick screening
      method for this population has not been established. Because CAIS is associated
      with a short vagina, measuring vaginal length could serve this purpose if normal
      standards were known. The authors endeavored to (1) prospectively confirm the
      incidence of CAIS, (2) identify normal standards of vaginal length, and (3)
      assess the usefulness of measuring vaginal length to screen for CAIS in girls
      with inguinal hernias. METHODS: Vaginal lengths were measured in 270 girls with
      inguinal hernias at a university hospital from 1991 to 2003. A fallopian tube was
      identified to exclude CAIS. If CAIS was suspected, gonadal tissue was sampled and
      karyotyping was performed. Linear regression analysis was performed, and 95%
      confidence intervals were calculated for individual values. RESULTS: Normal
      vaginal length for age was established. Three patients were found to have
      significantly short vaginas: 2 were confirmed to have CAIS, 1 did not (false
      positive). One other infant was proved to have CAIS despite having a normal
      vaginal length (false-negative). The incidence of CAIS in our study was 1.1%
      (3/270). CONCLUSIONS: This is the largest prospective study of the incidence of
      CAIS in girls with hernias. The authors found that 1.1% of premenstrual girls
      with inguinal hernias have this syndrome. The authors also provide standards for
      normal vaginal length in the pediatric population. Vaginal length increases
      predictably with age, and some patients with CAIS have significantly shorter
      vaginas. Vaginal length is not a perfect predictor of this disorder, but can be a
      useful adjunctive screening tool.

PMID- 15868574
TI  - Foregut duplications: is there an advantage to thoracoscopic resection?
AB  - PURPOSE: Thoracoscopy has an expanding role in the treatment of FD cysts
      (bronchogenic cysts and esophageal duplications). We examined this trend in our
      patients and reviewed our overall experience. METHODS: All charts of children
      undergoing surgery for foregut duplications (FDs) in 2 pediatric hospitals
      between 1992 and 2003 were retrospectively reviewed. Data gathered included age,
      weight, symptoms, diagnostic tests, operative technique, postoperative course,
      complications, and outcome. RESULTS: There were 39 children, with FD resected by
      thoracotomy in 21 patients, thoracoscopy in 11 patients (no conversions to open),
      cervical incision in 6 patients, and laparotomy in 1 patient for an FD near the
      gastroesophageal junction. Diagnosis was made by antenatal ultrasound in 7 cases.
      Four of these neonates had tachypnea or cough, and the rest were asymptomatic.
      Seventy-five percent of patients diagnosed postnatally presented with respiratory
      symptoms. Excision of isolated FD (without lung resection) was compared between
      those who had a thoracotomy (n = 16) vs thoracoscopy (n = 11). The age, weight,
      operating time, and anesthesia time were not different between the 2 groups.
      However, the thoracoscopy group had significantly fewer chest tube days (1.6 vs
      3.3 days) and a shorter hospital stay (2.6 vs 6.6 days). Intraoperative
      complications consisted of tracheal injury in 3 patients (2 thoracotomy, 1
      thoracoscopy) and esophageal mucosal injury in 2 patients (both thoracotomy),
      which were all recognized and repaired. CONCLUSION: Foregut duplications may
      present in a variety of ways and locations. Thoracoscopy is advantageous for
      isolated intrathoracic FDs.

PMID- 15868575
TI  - The first decade's experience with laparoscopic Nissen fundoplication in infants
      and children.
AB  - BACKGROUND/PURPOSE: Fundoplication for gastroesophageal reflux disease is a
      common procedure performed in infants and children. This report describes over a
      10-year experience with more than 1000 consecutive laparoscopic Nissen
      fundoplications. METHODS: Ages ranged from 5 days to 18 years and weight from 1.2
      to 120 kg. The procedures were performed using a 5 trocar technique and with 5-
      or 3-mm instruments depending on the size of the patient. Of 1050
      fundoplications, 1048 were completed successfully through laparoscopy. RESULTS:
      Average operative time dropped dramatically from 109 minutes for the first 30
      cases compared with 38 minutes for the last 30. Intraoperative and postoperative
      complications were 0.26% and 4.0%, respectively. Average time to discharge post
      fundoplication was 1.1 days. The wrap failure rate is 4.0%. CONCLUSIONS: This
      study shows in a large operative experience for 10 years that laparoscopic
      fundoplication is safe and effective in the pediatric population. Clinical
      results are comparable to the traditional open fundoplication but with a
      significant decrease in morbidity and hospitalization.

PMID- 15868576
TI  - Stretta as the initial antireflux procedure in children.
AB  - BACKGROUND: The Stretta procedure is an endoluminal antireflux procedure using
      radio frequency to induce collagen tissue contraction, remodeling, and modulation
      of lower esophageal sphincter physiology in an effort to treat gastroesophageal
      reflux disease (GERD). Although Stretta has been widely reported in the adult
      GERD literature as a viable initial surgical option, similar use in children has
      not been reported. The authors present the first report of Stretta as the initial
      antireflux procedure in children with GERD, evaluating indications, safety, and
      efficacy. METHOD: The charts of 8 children (aged 11-16 years) who received
      Stretta between January 2003 and September 2003 were retrospectively reviewed
      under an Institutional Review Board protocol. All patients had documented GERD
      preoperatively. Three children required concomitant feeding tube placement
      (percutaneous gastrostomy tube, group A). Five children with isolated severe GERD
      refractory to aggressive medical therapy received Stretta only (group B).
      RESULTS: Stretta was successfully completed in all 8 children. In group A, 1
      child developed a postoperative aspiration, which was successfully treated. All 3
      children had resolution of their GERD symptoms (ie, feeding intolerance, emesis)
      and were able to tolerate full enteral nutrition post-Stretta. In group B, 3 of 5
      children are currently off medications and asymptomatic on short-term follow-up
      (6-15 months). Of the remaining 2, 1 experienced symptomatic relief immediately
      postprocedure, but symptoms recurred off medications. Stretta was deemed
      unsuccessful in the remaining patient, and Nissen fundoplication was subsequently
      performed without difficulty. CONCLUSIONS: Stretta can be safely and successfully
      used as the initial antireflux procedure for children with GERD. Concomitant
      Stretta with PEG is an attractive option in children with preexisting GERD who
      require long-term feeding access. Longer follow-up and a larger patient
      population are needed to better confirm the safety and efficacy of Stretta
      presented in this report.

PMID- 15868577
TI  - A prospective comparison of thoracoscopic vs open anterior instrumentation and
      spinal fusion for idiopathic thoracic scoliosis in children.
AB  - BACKGROUND/PURPOSE: The management of scoliosis in children has been evolving.
      Anterior release, diskectomy, and anterior instrumentation and spinal fusion
      (AISF) may be of benefit compared with a combined anterior and posterior or a
      posterior-only approach. Because thoracoscopic AISF (TAISF) has the potential
      benefit of muscle sparing, superior cosmesis, and less pain, the authors decided
      to prospectively compare this newer technique with open AISF (OAISF) to evaluate
      whether the 2 approaches were equivalent. METHODS: All children with idiopathic
      thoracic scoliosis undergoing AISF at a single center were prospectively
      examined. One hundred fifty-five children who had a minimum of 1-year follow-up
      were included in the study. Descriptive statistics are reported as means and SDs.
      Groups were compared using the independent-samples t test with Levene's test for
      equality of variances; a 2-tailed P value of .05 or less was considered
      significant. RESULTS: Open AISF was performed in 114 patients and TAISF was
      performed in 41; there were 126 girls and 29 boys. Mean age at surgery was
      similar (14 +/- 3 vs 14.3 +/- 1.5 years; P = .5), as was weight (54.2 +/- 19 vs
      54.6 +/- 23 kg; P = .9). There were no differences in preoperative thoracic
      curves (48.5 degrees +/- 14 degrees vs 49.8 degrees +/- 7 degrees; P = .6) or in
      the number of vertebral levels instrumented (7.7 +/- 1.3 vs 7.6 +/- 0.7; P = .7).
      Operative time was shorter with OAISF (383 +/- 65 vs 508 +/- 98 minutes; P <
      .01), and there was less estimated blood loss (924 +/- 724 vs 1218 +/- 747 mL; P
      = .03). The OAISF group took longer to extubate (1.4 +/- 1.2 vs 1 +/- 0.3 days; P
      = .03) and had slightly greater chest tube drainage (1710 +/- 730 vs 1639 +/- 515
      mL; P = .5). At the 1-year follow-up, the thoracic curves were similar (17.5
      degrees +/- 8 degrees vs 15.2 degrees +/- 7.5 degrees; P = .1) and percentage
      correction of thoracic curves was also similar (64% vs 69%). CONCLUSIONS:
      Thoracoscopic AISF is safe and effective in correcting idiopathic childhood
      scoliosis. Correction of deformity with TAISF is equivalent to OAISF, although it
      takes longer and has more blood loss. However, it spares cutting muscle, uses
      smaller skin incisions, and appears to have superior cosmesis.

PMID- 15868578
TI  - Management and long-term follow-up of patients with types III and IV
      laryngotracheoesophageal clefts.
AB  - BACKGROUND: Laryngotracheoesophageal cleft (LTEC) is a rare congenital anomaly
      that occurs when the trachea and esophagus fail to separate during fetal
      development. The 2 most severe forms of LTEC are type III, with extension of the
      cleft from the larynx to the carina, and type IV, with extension of the cleft
      into one or both mainstem bronchi. METHODS: Over the past 25 years, we have
      accumulated an experience caring for 9 patients with severe LTEC, including 4
      with type III and 5 with type IV. RESULTS: Morbidity and mortality from severe
      LTEC often result from aspiration and chronic lung disease. Patients with types
      III (1/4) and IV (5/5) LTEC have an extremely high incidence of microgastria with
      a shortened esophagus for which fundoplication is ineffective. Because gastric
      feeding often does not initially increase stomach volume and may cause severe
      aspiration, we suggest early gastric division with later reconstruction of
      intestinal continuity in patients with microgastria. Postoperative
      tracheoesophageal fistulas have occurred in 6 of 9 patients. CONCLUSIONS:
      Generous interposition of vascularized tissue with a multiple-layer closure has
      helped to prevent further recurrences. Postoperative tracheomalacia may be
      managed with continuous positive airway pressure and may require customized
      endotracheal tubes. Evaluation of respiratory and digestive function, school
      performance, and quality of life for the surviving patients is described.

PMID- 15868579
TI  - Primary vs delayed surgery for spontaneous pneumothorax in children: which is
      better?
AB  - BACKGROUND: Controversy exists regarding the timing of surgery for spontaneous
      pneumothorax (SP), which can be performed either after the first development of
      pneumothorax or after a recurrent spontaneous pneumothorax has occurred.
      Treatment after recurrence is often adopted because of the purported low
      recurrence of SP treated nonoperatively and the historical morbidity of open
      surgery. However, the effectiveness of VATS (to video-assisted bullectomy and
      pleurodesis) has raised the possibility of performing primary VATS (PV) in all
      patients. The authors therefore hypothesized that PV is safe and effective for SP
      and sought to perform a cost-benefit analysis of PV vs secondary VATS (SV).
      METHODS: After institutional review board approval, consecutive patients with SP
      (1991-2003) and no comorbidities were retrospectively divided into PV vs SV.
      Demographics, recurrent pneumothorax after VATS, length of stay, and costs were
      compared by Student's t test/chi2. The predicted incremental cost of PV was (cost
      of PV) - [cost of nonoperative treatment x (1 - recurrence rate)] + cost of SV x
      recurrence rate. Data are means +/- SEM. RESULTS: There were 54 spontaneous
      pneumothoraces in 43 patients (11 bilateral), of whom 3 were excluded because of
      open thoracotomy. Of 51 pneumothoraces, nonoperative treatment was attempted in
      37, of whom 20 recurred and thus required SV. Primary VATS was performed in 14.
      Both groups had similar age, sex, weight, height, admission heart rate, and room
      air oxygen saturation. Total treatment length of stay was significantly shorter
      for PV vs SV (7.1 +/- 0.96 vs 10.5 +/- 1.2, P = .04). However, morbidity from
      recurrent pneumothorax after VATS occurred more frequently after PV than SV (4/14
      vs 0/20 P < .05). Based on the observed recurrence rate of 54%, performing PV on
      all patients with SP would increase cost by $4010 per patient and require a
      recurrence rate of 72% or more to financially justify this approach. CONCLUSIONS:
      Contrary to the hypothesis, the increased morbidity and cost do not justify a
      strategy of PV blebectomy/pleurodesis in children with SP. Instead, secondary
      treatment is recommended.

PMID- 15868580
TI  - Further experience with the operative management of asphyxiating thoracic
      dystrophy after pectus repair.
AB  - BACKGROUND/PURPOSE: Asphyxiating thoracic dystrophy (ATD) can occur years after a
      Ravitch-type repair of pectus excavatum, resulting in debilitating alteration in
      pulmonary function (PFT). An operation was devised to attempt repair of this
      deformity. METHODS: After institutional review board approval, the records of 10
      children (ages 9-18 years) with ATD that developed 4 to 12 years postpectus
      operation who underwent attempted repair of ATD were reviewed. Data obtained
      before ATD operation and at 6, 12, and 24 months afterward included chest
      computed tomography, pulmonary functions (PFT), and a quality of life
      questionnaire. The operation consisted of sternal split with rib graft placement
      to permanently hold the sternum apart. RESULTS: All children survived and the
      bone grafts healed solidly. Computed tomography showed a change from a flat to a
      round chest contour on cross section, with increased anteroposterior dimension.
      Two patients had no change in PFT at 24 months whereas the other 8 had 21% to 30%
      improvement in PFT parameters. All patients reported improved exercise tolerance,
      and 3 began sports activities who were previously unable to do so. Two patients
      on oxygen, essentially bedridden, are now active, breathing only room air. Seven
      of 10 patients continue to have cosmetic concerns. CONCLUSIONS: A small
      population of patients who had postoperative pectus repair developed severe,
      debilitating ATD. The repair described improves most patients, some dramatically,
      but does not significantly improve cosmetic appearance. The operation is
      undergoing further refinement to address these issues.

PMID- 15868581
TI  - Impact of pectus excavatum on pulmonary function before and after repair with the
      Nuss procedure.
AB  - BACKGROUND/PURPOSE: Patient reports of preoperative exercise intolerance and
      improvement after surgical repair of pectus excavatum (Pex) have been documented
      but not substantiated in laboratory studies. This may be because no study has
      been large enough to determine if pulmonary function tests (PFTs) in the Pex
      population are significantly different from the normal population, and none has
      assessed improvement in pulmonary function after Nuss bar removal. METHODS: The
      authors studied PFT results in 408 Pex patients before repair and in a subset of
      45 patients after Nuss procedure and bar removal. Significance of differences in
      percent predicted (using Knudson's equations) was tested using t tests
      (parametric) or sign tests (nonparametric). Normal was defined as 100% of
      predicted for forced vital capacity (FVC), forced expired volume in 1 second
      (FEV1), and forced expiratory flow (FEF25%-75%). RESULTS: Preoperatively, FVC and
      FEV1 medians were lower than the normal by 13%, whereas the FEF 25-75 median was
      lower than normal by 20% (all P < .01). The postoperative group had statistically
      significant improvement after surgery for all parameters. Patients older than 11
      years at the time of surgery had lower preoperative values and larger mean post
      bar removal improvement than the younger patients. An older patient with a
      preoperative FEF25-75 score of 80% of normal would be predicted by these data to
      have a postoperative FEF25-75 of 97%, indicating almost complete normalization
      for this function. CONCLUSIONS: These results demonstrate that preoperatively Pex
      patients as a group have decreased lung function relative to normal patients.
      After Nuss procedure and bar removal, we show a small but significant improvement
      in pulmonary function. These results are consistent with patient reports of
      clinical improvement and indicate the need for more in-depth tests of
      cardiopulmonary function under exercise conditions to elucidate the mechanism.

PMID- 15868582
TI  - The minimally invasive Nuss technique for recurrent or failed pectus excavatum
      repair in 50 patients.
AB  - PURPOSE: The aim of this study was to demonstrate the efficacy of the minimally
      invasive technique for recurrent pectus excavatum. METHODS: Fifty patients with
      recurrent pectus excavatum underwent a secondary repair using the minimally
      invasive technique. Data were reviewed for preoperative symptomatology, surgical
      data, and postoperative results. RESULTS: Prior repairs included 27 open Ravitch
      procedures, 23 minimally invasive (Nuss) procedures, and 2 Leonard procedures.
      The prior Leonard patients were also prior Ravitches and are therefore counted
      only once in the analyses. The median age was 16.0 years (range, 3-25 years). The
      median computed tomography index was 5.3 (range, 2.9-20). Presenting symptoms
      included shortness of breath (80%), chest pain (70%), asthma or asthma symptoms
      (26%), and frequent upper respiratory tract infections (14%). Both computed
      tomography scan and physical exam confirmed cardiac compression and cardiac
      displacement. Cardiology evaluations confirmed cardiac compression (62%), cardiac
      displacement (72%), mitral valve prolapse (22%), murmurs (24%), and other cardiac
      abnormalities (30%). Preoperative pulmonary function tests demonstrated values
      below 80% normal in more than 50% of patients. Pectus repair was done using a
      single pectus bar (66%), 2 bars (32%), or 3 bars (2%). Stabilizers were used in
      88% of the patients. Median length of surgical time did not significantly differ
      from that of primary surgeries. Complications were slightly higher than those in
      primary repairs and included pneumothorax requiring chest tube (14%), hemothorax
      (8%), pleural effusion requiring drainage (8%), pericarditis (4%), pneumonia
      (4%), and wound infection (2%). There were no deaths or cardiac perforations.
      Initial postoperative results were excellent in 70%, good in 28%, and fair in 2%.
      Late complications of bar shift requiring revision occurred in 8%. Seventeen
      patients have had bar removals with 9 patients being more than 1 year
      postremoval. For the 17 patients who are postremoval, excellent results have been
      maintained in 8 (47%), good in 7 (41%), fair in 1 (6%), and failed in 1 (6%).
      There have been no recurrences postremoval. CONCLUSIONS: Although failed or
      recurrent pectus excavatum repairs are technically more challenging, reoperative
      correction by the Nuss procedure has met with excellent success.

PMID- 15868583
TI  - Surgical management of perineal masses in patients with anorectal malformations.
AB  - BACKGROUND: The aim of this study was to review the outcome of surgical
      management of various types of perineal masses encountered in patients with
      anorectal malformations (ARM). METHODS: Retrospective review from 2 large
      pediatric anorectal referral centers. RESULTS: Twenty-two patients with a
      perineal mass were identified in more than 2000 patients treated for an ARM over
      a 15-year period. The 22 patients (4 men) represented all levels of severity of
      ARMs. The lesions were of 3 types: lipomas (n = 10), vascular anomalies (n = 4),
      and hamartomas/choristomas (n = 8). The lipomas were carefully removed from
      between the muscle fibers during the posterior sagittal anorectoplasty. The
      vascular anomalies (3 of 4 were hemangiomas) underwent magnetic resonance imaging
      preoperatively, but none were found to invade deeply and all were excised at the
      time of the posterior sagittal anorectoplasty. The hamartomas/choristomas all
      occurred in women, and 50% arose as a pedunculated mass from the vulva. The
      lesions contained tissues such as glia, osteoid, nephrogenic rests, and
      endocervical-type mucosa. One was initially misinterpreted as a teratoma,
      prompting a wider excision. This and all subsequent patients have been correctly
      diagnosed pathologically as having either hamartomas or choristomas, which were
      not widely excised. Follow-up ranges from 5 months to 12 years. Six of the 10
      lipoma patients are continent. One vascular anomaly was re-excised and there was
      minor wound separation in another. None of the hamartoma/choristoma lesions
      recurred. CONCLUSION: The presence of unusual perineal masses can add to the
      complexity of ARMs; however, most of these lesions can be carefully excised with
      preservation of the muscle complex and ultimate continence. Hamartomatous lesions
      can be mistaken for teratomas but do not require aggressive excision with clear
      margins.

PMID- 15868584
TI  - Rectal prolapse following posterior sagittal anorectoplasty for anorectal
      malformations.
AB  - PURPOSE: Rectal prolapse is a known postoperative problem in children with
      anorectal malformations. The aims of this study were to determine the incidence
      of significant rectal prolapse (>5 mm), to objectively quantify its predisposing
      factors, and to offer recommendations as to its prevention and surgical
      treatment. METHODS: The authors reviewed their series of 1619 patients with
      anorectal malformations; 1169 underwent primary posterior sagittal anorectoplasty
      (PSARP) at their institution between 1980 and 2002, and complete records were
      available for 833. The series was analyzed for incidence of prolapse, type of
      anorectal malformation, status of the sacrum, muscle quality, associated
      vertebral and spinal anomalies, and postoperative constipation. A specific
      technique for prolapse repair was used. RESULTS: Of 833 patients, 45 developed
      significant rectal prolapse (3.8%). The mean age at the time of PSARP was 0.73
      years (range, 0.19-5 years). The average time to recognition of prolapse
      following PSARP was 13.1 months. Of these 45 patients, 32 required surgical
      repair and of those, 3 required a second surgical repair. The incidence of
      prolapse varied by complexity of anorectal defect: cloaca (6.2%), rectobladder
      neck fistula (6.8%), rectourethral fistula (5.4%), rectovestibular fistula
      (1.2%), rectal atresia (0%), and rectoperineal fistula (0%). There was a
      significantly increased incidence of prolapse in patients with a low muscle
      quality score and in patients with vertebral anomalies (20% vs 3.2%). The
      presence of a tethered cord and an abnormal sacral ratio did not correlate with
      an increased incidence of prolapse. Twenty-two patients developed prolapse
      following colostomy closure, and of these, 12 (55%) suffered from constipation.
      CONCLUSIONS: The overall incidence of significant rectal prolapse following PSARP
      is low. Prevention of prolapse with the PSARP technique may be because of key
      technical steps. Patients with higher anorectal malformations, poorer muscle
      quality, and vertebral anomalies had a greater risk of developing postoperative
      rectal prolapse. The presence of tethered cord and quality of the sacrum were not
      predictive of postoperative prolapse. Constipation seems to be a factor in the
      development of prolapse.

PMID- 15868585
TI  - Hirschsprung's disease in Japan: analysis of 3852 patients based on a nationwide
      survey in 30 years.
AB  - BACKGROUND/PURPOSE: The introduction of laparoscope and transanal endorectal pull
      through has caused a revolution in the operative procedures for Hirschsprung's
      disease. To study the changing profile of Hirschsprung's disease in Japan, the
      authors carried out a national survey. METHOD: Patient data were collected in 3
      phases: group 1, 1628 patients between 1978 and 1982; group 2, 1121 patients
      between 1988 and 1992; and group 3, 1103 patients between 1998 and 2002,
      respectively. RESULTS: The incidence was 1:4697, 1:5544, and 1:5343 and the
      male/female ratio was 3.0:1, 3.4:1, and 3.0:1 in each group, respectively.
      Patients weighing less than 2500 g at birth increased to 10.4% in group 3,
      whereas they were 6.5% in group 2 and 5.5% in group 1. The patients with a family
      history also increased to 6.0% in group 3, in comparison with 2.8% in group 2 and
      3.0% in group 1. The incidence of associated anomalies increased over time, 11.1%
      in group 1, 16.3% in group 2, and 21.2% in group 3. Mutations of genes were found
      in 4 of the 23 patients examined. The extent of aganglionosis was almost the same
      in each group. Regarding the definitive operation, the procedures without
      laparotomy, including transanal endorectal pull-through, increased up to 42.6% in
      group 3 but 0% in groups 1 and 2. The frequency that a primary operation without
      stoma was performed also increased. The age at definitive operation decreased in
      group 3. The incidence of preoperative and postoperative enterocolitis also
      decreased over time. The mortality was decreased over time, 7.1%, 4.9%, and 3.0%
      for groups 1, 2, and 3, respectively. CONCLUSIONS: The authors analyzed 3852
      Japanese patients over 3 decades. The ratio of patients with a low birth weight,
      associated anomalies, or a family history was increased in the last 10 years. A
      primary operation without laparotomy has thus become the procedure of choice for
      a definitive operation.

PMID- 15868586
TI  - Total colonic Hirschsprung's disease: a 28-year experience.
AB  - PURPOSE: The aim of this study was to review outcomes after surgical treatment of
      total colonic Hirschsprung's disease (TCH). METHODS: Twenty-five records of
      patients with TCH treated between 1974 and 2002 were reviewed. Follow-up data
      were collected using a standardized questionnaire. Objective functional outcome
      was assessed using a scoring system. RESULTS: Twenty patients had aganglionosis
      of the colon and distal ileum, 5 of whom had a more extensive condition. One of
      these 5 patients underwent an endorectal pull-through (ERPT), 1 underwent
      intestinal transplantation, and 3 died. Four of the remaining 20 patients
      underwent a primary ERPT, 16 received a stoma as neonates followed by ERPT in 12,
      and a Martin-Duhamel procedure or Swenson's operation in 3 (median age, 10.5
      months); 1 remains with an ostomy. Postoperative complications included
      enterocolitis (55%), anal stricture (25%), and perineal excoriation (20%). Mean
      follow-up were 17.5 years (+/-11.1 years). Eighty-nine percent were free of
      recurrent enterocolitis. Frequency of bowel movements is 1 to 5 per day in 82% of
      the patients, 18% have 6 or more bowel movements per day. Occasional soiling is
      noted in 40% (one third of those requiring nighttime diapers). Overall functional
      outcome was good in 83%. Those patients with the longest follow-up periods had
      the best stooling scores (P = .04). CONCLUSIONS: Surgical treatment of TCH is
      associated with a number of complications including recurrent enterocolitis and
      anal strictures. Long-term outcome is quite favorable.

PMID- 15868587
TI  - Quality assessment for Wilms' tumor: a report from the National Wilms' Tumor
      Study-5.
AB  - BACKGROUND/PURPOSE: Surgical technique impacts both local tumor stage and risk of
      local recurrence in Wilms' tumor. A surgical quality assurance program was part
      of National Wilms' Tumor Study-5 to assess protocol compliance. METHODS: Surgical
      checklists, operative, and pathology reports were reviewed concurrently to arrive
      at the final local tumor stage. If a protocol violation occurred, a letter was
      sent to the responsible surgeon. Tumor laterality, extent, type of resection,
      contralateral exploration, node involvement, spills, and local recurrence were
      reviewed. Relative risk and logistic regression analyses were performed. RESULTS:
      There were 1305 nephrectomies. Lymph node sampling was not performed in 117 (9%)
      patients: stage I, 41 (11.5%), stage II, 57 (12%), and stage III, 19 (4%). Of
      importance, 41% (187/457) of stage III cases were designated stage III solely on
      the basis of positive lymph nodes. Tumor spill occurred in 19.3% (253/1305) of
      children. Fifty-four local spills were in stage II tumors and 97 in stage III.
      Diffuse spill occurred in 102 patients with stage III tumors. Seventeen
      preoperative and 13 intraoperative biopsies were performed. Intraoperative tumor
      rupture was the most common cause of tumor spill accounting for 139 (55%) spills.
      Nineteen (7.5%) children were upstaged, receiving more intensive therapy because
      of spill. Included in the group were 3 of 17 preoperative biopsies and 5 of 13
      intraoperative biopsies. Spills (13/253) were determined to be avoidable. Eight
      were biopsies, 5 because tumor was transected in the renal vein (4) or ureter
      (1). In stage II patients where lymph nodes were not sampled, there is an
      increase in local relapse rate that did not achieve statistical significance
      because of the small number of events. CONCLUSIONS: Although most surgeons
      complied with the surgical guidelines, numerous deviations were identified
      including failure to sample lymph nodes (117 cases) and unnecessary biopsies
      leading to tumor spill (30 cases). Protocol violations have an adverse impact on
      tumor staging, potentially increasing the risk for local tumor recurrence or
      intensity and toxicity of therapy.

PMID- 15868588
TI  - Partial splenectomy before a hematopoietic stem cell transplantation in children.
AB  - Hematopoietic stem cell (HSC) engraftment is delayed in children with
      hypersplenism, and splenectomy may improve HSC engraftment. However, the use of
      total splenectomy in children is limited because of concerns for postsplenectomy
      sepsis. In this study, the authors sought to assess the role of partial
      splenectomy for children with hypersplenism undergoing HSC transplantation.
      METHODS: Five children with a variety of conditions and associated hypersplenism
      underwent partial splenectomy before an HSC transplantation at the authors'
      institution between 2000 and 2003. Primary outcome measures were rates of
      neutrophil and platelet engraftment. Secondary outcome measures included
      perioperative complications, splenic regrowth, graft-versus-host disease, and
      infection rate. All outcomes were compared with recipients of an HSC transplant
      from both age-matched nonsplenectomized children (n = 497) and hypersplenic
      children who underwent total splenectomy (n = 10). Outcomes were compared using
      Wilcoxon's rank sum test. RESULTS: The rate of both neutrophil and platelet
      engraftment was faster in children who underwent either partial or total
      splenectomy as compared with nonsplenectomized children (mean rates of neutrophil
      engraftment were 26, 19, and 19 days for the nonsplenectomy, total splenectomy,
      and partial splenectomy groups, respectively; mean rates of platelet engraftment
      were 97, 37, and 45 days for the nonsplenectomy, total splenectomy, and partial
      splenectomy groups, respectively). Graft-versus-host disease rates were similar
      between the 3 groups. The mean percentage of splenic regrowth after partial
      splenectomy was 39%. There were no perioperative complications. CONCLUSIONS:
      Partial splenectomy may be safely performed before HSC transplantation and,
      similar to total splenectomy, may improve the rate of HSC engraftment. Although
      this series has a limited number of patients, the use of partial splenectomy
      appears to be safe and may allow for splenic salvage to minimize the risk of
      postsplenectomy sepsis.

PMID- 15868589
TI  - Management of fetal mediastinal teratoma.
AB  - BACKGROUND/PURPOSE: Mediastinal teratomas are rare congenital germ cell tumors
      that prenatally can compress mediastinal structures and cause hydrops. Two
      possible presentations of massive fetal mediastinal teratoma include hydrops
      leading to fetal demise, or fetal esophageal and airway compression causing late
      gestation polyhydramnios and preterm labor. The authors present 2 cases of fetal
      mediastinal teratoma that illustrate successful strategies for either of these
      presentations. METHODS: A 37-year-old woman carrying a fetus with a mediastinal
      mass and secondary hydrops at 23 weeks of gestation underwent in utero resection
      of the mass. Delivery was by cesarean delivery at 25 weeks because of preterm
      labor. A 24-year-old mother carrying a fetus with a mediastinal mass and severe
      polyhydramnios at 36 weeks of gestation underwent an ex utero intrapartum therapy
      procedure for establishment of an airway and tumor resection on uteroplacental
      support. RESULTS: These strategies resulted in physiologic improvement in the
      first case and controlled resection and resuscitation in the second. The first
      patient had significant sequelae of prematurity including bronchopulmonary
      dysplasia but is currently well at 9 months of age. The second patient is well at
      1 year of age. CONCLUSIONS: Massive fetal mediastinal teratoma can result in
      fetal or neonatal mortality by a variety of mechanisms. Optimal prenatal and
      perinatal management is required to salvage fetuses compromised by this lesion.

PMID- 15868590
TI  - Sentinel lymph node biopsy for melanoma and other melanocytic tumors in
      adolescents.
AB  - BACKGROUND/PURPOSE: Melanoma is rare, accounting for only 1% of all pediatric
      malignancies. The management of pediatric melanoma is controversial but largely
      parallels that of an adult occurrence. Sentinel lymph node biopsy (SLNBX) has
      become a standard of care for adults with melanoma, but the role of this
      procedure in the staging of pediatric patients remains to be established. The
      goal of this study was to determine outcomes and complications of children and
      adolescent patients undergoing SLNBX at the authors' institution. METHODS: A
      retrospective review of patients younger than 21 years (N = 20) undergoing SLNBX
      for melanoma or other melanocytic skin lesions at the University of Colorado
      Health Science Center between 1996 and 2003 was conducted. RESULTS: Sentinel
      lymph node biopsy was successful in all 20 patients, and 8 patients (40%) were
      found to have metastases within the sentinel node. As in adults, the sentinel
      node status correlates with primary tumor depth. No complications occurred in
      patients undergoing SLNBX, but 4 clinically significant complications (57%)
      occurred in the 7 patients undergoing a completion lymph node dissection. At 33
      months median follow-up, all patients were disease free. CONCLUSIONS: Sentinel
      lymph node biopsy can be successfully and safely performed in pediatric patients
      for melanoma and atypical nevi. However, the prognostic information and
      therapeutic implications of SLNBX results for children and adolescents remain
      unclear. Completion lymph node dissection for microscopic disease is a morbid
      procedure with uncertain benefit to pediatric or adult patients with a positive
      SLNBX result. Long-term follow-up data are needed before SLNBX can become a
      standard of care in pediatric melanoma or as a diagnostic tool to distinguish the
      atypical Spitz nevus from melanoma.

PMID- 15868591
TI  - Adeno-associated virus vector-mediated delivery of pigment epithelium-derived
      factor restricts neuroblastoma angiogenesis and growth.
AB  - PURPOSE: The purpose of this study was to evaluate the ability of adeno
      associated virus (AAV) vector-mediated delivery of pigment epithelium-derived
      factor (PEDF) to inhibit neuroblastoma (NB) xenograft growth. Pigment epithelium
      derived factor was chosen for this study because, in addition to being a potent
      inhibitor of angiogenesis, it is capable of inducing neuronal differentiation.
      METHODS: Cohorts of mice received either recombinant AAV encoding human PEDF
      (rAAV-hPEDF) at a range of doses or control vector via tail vein. Subsequent
      hPEDF expression was measured by enzyme-linked immunoassay. After 6 weeks, the
      mice were given human NB cells by retroperitoneal injection and then killed 5
      weeks later. Tumor weight, microvessel density, tumor differentiation, apoptosis,
      and levels of intratumoral vascular endothelial growth factor (VEGF) expression
      were determined at that time. In subsequent cohorts of mice, AAV-mediated murine
      PEDF expression was tested against both human NB xenografts and murine tumors.
      RESULTS: In a series of in vitro studies, PEDF was shown to inhibit endothelial
      cell activation and to stimulate differentiation of NB cell lines. After tail
      vein injection of rAAV-hPEDF, stable transgene expression was generated and
      correlated with levels of vector administration. Human NB xenograft growth was
      restricted by hPEDF in a dose-dependent fashion. Intratumoral VEGF expression and
      microvessel density were decreased, and tumor cell apoptosis was increased in
      PEDF-treated mice. CONCLUSIONS: Treatment with PEDF had a significant impact on
      NB growth in mice when delivered continuously using a gene therapy-mediated
      approach. The activity of PEDF appears to be mediated in part by inhibition of
      tumor-induced angiogenesis through down-regulation of tumor-elaborated VEGF, with
      subsequent intratumoral apoptosis. Furthermore, hPEDF was able to induce NB
      differentiation in vitro and in vivo. In addition, antitumor efficacy was seen
      when mouse PEDF was used to treat syngeneic murine tumors. In our murine models,
      gene therapy-mediated delivery of PEDF appears promising for the treatment of
      neuroblastoma.

PMID- 15868592
TI  - Neuroblastoma-induced inhibition of dendritic cell IL-12 production via
      abrogation of CD40 expression.
AB  - BACKGROUND/PURPOSE: CD40 expression by dendritic cells (DCs) critically regulates
      their maturation/antitumor activity. CD40-CD40 ligand (CD40L) signaling
      stimulates DC-mediated IL-12 production/cytotoxicity. Recent studies suggest that
      neuroblastoma (NB)-derived gangliosides impair DC maturation, IL-12 secretion,
      and NK/T-cell activity. Neuroblastoma ganglioside-mediated abrogation of CD40
      expression by DC and tumor-induced tolerance has not been studied. The purpose of
      this study is to determine if NB inhibits DC IL-12 production via CD40. The
      contributory role of the NB-derived ganglioside GM3 in this process is also
      examined. METHODS: Dendritic cells were generated from bone marrow of mice
      injected with saline (control) or murine NB. Control DCs were matured with or
      without GM3. Dendritic cells were cocultured with NB cells treated with or
      without a ganglioside synthesis inhibitor. Dendritic cell groups were analyzed
      for maturation/costimulatory markers. Control and tumor-derived DC were
      stimulated with CD40L or Staphylococcus aureus and studied for IL-12 expression.
      RESULTS: CD40 expression on DC generated from NB bearing mice decreased by 64% (P
      < .001). GM3 down-regulated DC maturation and CD40 expression. Only CD40
      dependent IL-12 production was abrogated (60%, P < .01) in DC derived from NB
      bearing mice. Dendritic cell capacity to synthesize IL-12 remained intact.
      CONCLUSIONS: Neuroblastoma-induced inhibition of DC function may result from
      ganglioside-mediated CD40 signaling deficiency. Strategies to bypass/augment CD40
      CD40L signaling may improve current NB immunotherapies.

PMID- 15868593
TI  - Results of multimodal treatment for desmoplastic small round cell tumors.
AB  - PURPOSE: Desmoplastic small round cell tumors (DSRCTs) are rare aggressive
      neoplasms that frequently present with large symptomatic intraabdominal masses.
      We examined the effects of multimodal therapy including induction chemotherapy,
      aggressive surgical debulking, and external beam radiotherapy on patients with
      DSRCT. METHODS: Institutional Review Board permission was obtained. Sixty-six
      patients were diagnosed by histology, immunohistochemistry, and or cytogenetics
      as having DSRCT at our institution from July 1, 1972, to July 1, 2003. Data were
      collected on patient demographics, presenting symptoms, tumor location and
      extent, treatment regimen, and overall survival. RESULTS: A majority of patients
      were male (91%), Caucasian (85%), and with a median age of 19 (7-58) years old at
      diagnosis. The most common presenting complaint was an intraabdominal mass (64%).
      In 63 patients (96%), the primary tumor was located in the abdomen or pelvis.
      Thirty-three (50%) had positive lymph nodes and 27 (41%) had distant parenchymal
      metastases at diagnosis. Overall, 3- and 5-year survivals were 44% and 15%,
      respectively. Twenty-nine of these patients (44%) underwent induction
      chemotherapy (P6), surgical debulking, and radiotherapy. Three-year survival was
      55% in those receiving chemotherapy, surgery, and radiotherapy vs 27% when all 3
      modalities were not used (P < .02). Gross tumor resection was highly significant
      in prolonging overall survival; 3-year survival was 58% in patients treated with
      gross tumor resection compared to no survivors past 3 years in the nonresection
      cohort (P < .00001). Ten patients (15%) have no evidence of disease with a median
      follow-up of 2.4 years (range, 0.4-11.2 years). CONCLUSIONS: Multimodal therapy
      results in improved survival in patients with DSRCT. Aggressive surgical
      resection of these extensive intraabdominal neoplasms correlates with improved
      patient outcome.

PMID- 15868594
TI  - Characteristics and outcomes of rhabdomyosarcoma patients with isolated lung
      metastases from IRS-IV.
AB  - PURPOSE: To better understand outcomes in children with rhabdomyosarcoma (RMS)
      and lung-only metastatic disease, the authors reviewed the experience from
      Intergroup Rhabdomyosarcoma Studies IV Pilot and IV. METHODS: Patients with lung
      only (n = 46) vs other sites of metastatic disease (n = 234) were reviewed using
      patient charts and the database of Children's Oncology Group (COG). RESULTS:
      Sixteen percent of patients with RMS and metastatic disease had isolated lung
      metastases. Thirty-one (67%) had more than 5 metastatic lung lesions. These were
      bilateral in 34 (74%). Only 6 patients were biopsied at diagnosis. Sixteen
      children (35%) did not receive any lung radiotherapy. Patients that received lung
      radiotherapy had fewer lung recurrences ( P = .04), although this has no
      significant impact on overall survival (OAS, 47% radiotherapy vs 31% no
      radiotherapy). Compared with patients with other sites of metastatic disease,
      patients with lung-only metastases have a greater proportion of favorable
      histology (67% vs 39%, P = .0017), negative nodal involvement (67% vs 32%, P =
      .0013), and parameningeal primaries (39% vs 12%) and a smaller proportion of
      extremity primaries (20% vs 33%, P = .0005 for site of primary tumor). Overall
      survival at 4 years for lung-only metastases was not significantly different from
      other single-site metastasis (42% vs 34%). Survival was not improved for
      unilateral disease or fewer than 5 metastatic lesions. Factors associated with
      diminished OAS include unfavorable histology (P = .0001) and age >10 years (P =
      .015). CONCLUSIONS: Children with RMS and lung-only metastases usually present
      with extensive bilateral disease that is frequently not biopsied nor given
      protocol-recommended radiotherapy (XRT). However, outcome is comparable, although
      slightly better, than patients with other single-site metastasis.

PMID- 15868595
TI  - Failure of cholecystokinin-octapeptide to prevent TPN-associated gallstone
      disease.
AB  - PURPOSE: Gallstone formation is a common problem in neonates on prolonged courses
      of total parenteral nutrition (TPN). The authors hypothesized that the use of
      cholecystokinin-octapeptide (CCK), given at the time of TPN administration, would
      prevent gallstone formation in a high-risk group of patients with TPN. METHODS: A
      prospective, randomized, blinded, controlled trial of neonates who were on a
      prolonged course of TPN for prematurity (25 infants), necrotizing enterocolitis
      (NEC, 8 infants), or abdominal surgery (5 infants) were selected randomly to
      receive CCK vs placebo. Patients remained on the study until taking more than 50%
      of energy enterally. Children were recalled between 2 and 4 years after
      completing TPN for ultrasonographic examination of their hepatobiliary tree.
      RESULTS: Neonates (38 studied) required a mean (+/-SD) of 33 +/- 16 days of TPN.
      Cholelithiasis was detected in 4 (10%) infants. Cholecystokinin-octapeptide was
      not effective in preventing the formation of gallstones (3 stones in infants
      receiving CCK, P = .51). Diagnosis (P = .56), birth weight (P = .54), gestational
      age (P = .18), and duration of TPN (P = .53) did not correlate with gallstone
      formation. To address the management of these stones, all 4 were placed on a
      prolonged course of ursodeoxycholic acid (mean duration, 11.6 +/- 5.4 months).
      Two additional infants (not in the original study) with TPN-associated gallstone
      disease were also given a trial of ursodeoxycholic acid. Serial ultrasounds were
      performed every 6 months. No patient achieved any degree of stone dissolution.
      One patient underwent cholecystectomy for symptomatology. CONCLUSIONS: Total
      parenteral nutrition-associated gallstones were detected in 10% of children, and
      most are nonsymptomatic. Cholecystokinin-octapeptide prophylaxis was not
      effective in preventing TPN-associated gallstones. In addition, the use of
      ursodeoxycholic acid did not dissolve gallstones, once identified. Future methods
      will be needed to address the prevention and treatment of these stones.

PMID- 15868596
TI  - Liver transplantation in children younger than 1 year--the Cincinnati experience.
AB  - BACKGROUND/PURPOSE: The success of pediatric orthotopic liver transplantation
      (OLTxp) has improved greatly since its widespread application in the 1980s. No
      group has benefited more from this than infants younger than 1 year. The authors
      reviewed their experience in the management and outcome of children who underwent
      OLTxp when they were younger than 1 year. METHODS: A retrospective review of the
      medical records of patients who at the time of OLTxp were younger than 1 year was
      performed. Patients were stratified according to the period when transplanted.
      RESULTS: Eighty-one infants younger than 1 year underwent OLTxp. End-stage liver
      disease secondary to biliary atresia was the most common indication for
      transplantation. The overall survival was 77%. One-year patient and graft
      survival improved from 58% and 50% in the period 1986-1989, respectively, to 88%
      and 81% in the period 2000-2003, respectively. Technical complications such as
      hepatic artery thrombosis (n = 5) and portal vein thrombosis (n = 8) occurred,
      and although 4 patients required retransplantation, all but one survived.
      Complications associated with immunosuppression, sepsis/multisystem organ failure
      (MSOF) (n = 11), and posttransplant lymphoproliferative disease (PTLD) (n = 1)
      were the most common cause of poor outcome. CONCLUSIONS: Successful OLTxp in
      infants is possible with improved posttransplant survival during the study
      period. Technical complications (hepatic artery thrombosis/portal vein
      thrombosis) may require retransplantation but were uncommon causes of patient
      loss. Multisystem organ failure was the most significant adverse complication.
      The consequences of immunosuppression (MSOF/PTLD) were the most common cause of
      patient loss. Further improvement in overall survival will require better
      immunosuppressive strategies.

PMID- 15868597
TI  - Evolutionary experience with immunosuppression in pediatric intestinal
      transplantation.
AB  - BACKGROUND/PURPOSE: Intestinal transplantation has developed to become the
      standard of care for patients with irreversible intestinal failure who are not
      responding to total parenteral nutrition. Once considered experimental, it has
      taken time and much effort for the procedure to become a clinical reality, with
      final acceptance primarily because of the vastly improved outcomes. Advances and
      novel modifications in immunosuppression have been at the forefront of these
      improvements. The authors review their evolutionary experience with intestinal
      transplantation, particularly relating changes in immunosuppression protocols to
      improved outcomes. METHODS: From July 1990 to December 2003, 122 children
      received 129 intestinal containing allografts (70 liver/intestine, 42 isolated
      intestine, 17 multivisceral). Mean age was 5.3 +/- 5.2 years, and 55% were boys.
      Indications for transplantation were mostly short gut syndrome. The allografts
      were cadaveric, ABO identical (except one), with no immunomodulation. Bone marrow
      augmentation was used in 29% of the recipients since 1995. T-cell
      lymphoctytotoxic crossmatch was positive in 24% cases. Immunosuppression
      protocols can be divided into 3 categories: (i) maintenance tacrolimus and
      steroids (n = 52, 1990-1995, 1997-1998); (ii) addition of induction therapy with
      cyclophosphamide (n = 16, 1995-1997) then daclizumab (n = 24, 1998-2001). A third
      immunosuppressive agent was added in either group where increased
      immunosuppression was indicated; (iii) pretreatment/induction with antilymphocyte
      conditioning and steroid-free posttransplantation tacrolimus monotherapy (n = 37,
      2002-2003). In this later group, if clinically stable at 60 to 90 days
      posttransplantation, and no recent rejection, the tacrolimus was weaned by
      decreasing frequency of dosing. RESULTS: The overall Kaplan-Meier patient/graft
      survival was 81%/76% at 1 year, 62%/60% at 3 years, and 61%/51% at 5 years.
      Survival continues to improve, with 1-year patient/graft survival being 71%/62%,
      77%/75%, and 100%/100% for groups (i), (ii), and (iii), respectively. Acute
      intestinal allograft rejection has decreased markedly in group (iii). The rate of
      infectious diseases, such as cytomegalovirus and Epstein-Barr virus, is lowest in
      group (iii). Graft-versus-host disease has not significantly increased with the
      latest protocol. Most importantly, the overall level of immunosuppression
      requirements has decreased markedly, with most patients in group (iii) being on
      monotherapy. Of these, most had their monotherapy weaned down to spaced doses,
      something never systematically attempted or achieved in pediatric intestinal
      transplantation. CONCLUSIONS: Intestinal transplantation has progressed markedly
      over the last 13 years. Although there have been modifications in all aspects of
      the procedure, the story of intestinal transplantation has been the evolution of
      successful immunosuppression regimens. Our latest pretreatment/induction
      conditioning and posttransplantation monotherapy strategy improves graft
      acceptance and lowers subsequent immunosuppression dosing requirements. It is
      expected this will overcome many of the complications related to the previously
      high immunosuppression requirements. Minimization of immunosuppression with
      avoidance of steroid therapy offers profound long-term benefits, especially in
      the pediatric population. The patients still remain challenging and complex in
      every aspect; however, these advances offer significant hope to both patients and
      caregivers alike.

PMID- 15868598
TI  - Laparoscopic vs open surgical approach for intussusception requiring operative
      intervention.
AB  - PURPOSE: Laparoscopy has recently been used to treat intussusception that cannot
      be reduced radiologically. The effectiveness and practical nature of this
      approach has been questioned. METHODS: This study retrospectively analyzed the
      authors' experience with this laparoscopic approach and compared this to the
      conventional open laparotomy procedure. RESULTS: Sixteen patients were treated
      via laparoscopy, with 2 of these requiring conversions to an open procedure
      (12.5%). Twenty-five patients underwent an open reduction. Operative time was not
      significantly different (P = .698) between the laparoscopic (49.56 +/- 26.40
      minutes) and open groups (45.00 +/- 24.74). Length of stay, however, was
      significantly reduced (P = .005) in the laparoscopic group (3.00 +/- 1.31 days)
      compared to the open group (4.52 +/- 1.98). Total hospital charges were lower in
      the laparoscopic group ($8171 +/- 2595) compared to the open group ($11,672 +/-
      5466); this difference was not significant (P = .088). There were no significant
      differences in intra- or postoperative complication rates (P = .637) between the
      2 approaches. CONCLUSIONS: Although there remains a group who will require a
      conversion to an open procedure, the laparoscopic approach should be considered a
      safe and effective option for all children who do not respond to a radiological
      reduction.

PMID- 15868599
TI  - Surgical treatment of malrotation after infancy: a population-based study.
AB  - PURPOSE: Because malrotation most commonly presents in infants, treatment
      recommendations for older children (>1 year) have been based on data obtained
      from small case series. The purpose of this study was to use a large national
      database to determine the clinical significance of older children presenting with
      malrotation to develop treatment recommendations for this group. METHODS: Records
      of children undergoing a Ladd's procedure were identified in the Kids' Inpatient
      Database, an administrative database that contains all pediatric discharges from
      27 states during 2000. Patient characteristics, associated diagnoses, operations
      performed, and mortality were evaluated. Discharge weighting was used to obtain a
      national estimate of the number of children older than 1 year treated for
      malrotation. RESULTS: Two hundred nineteen older children (>1 and <18 years)
      undergoing a Ladd's procedure were identified in the database. One hundred sixty
      four (75%) of these patients were admitted for treatment of malrotation, whereas
      most of the remaining 55 patients (25%) were admitted for another diagnosis and
      underwent a Ladd's procedure incidental to another abdominal operation. Seventy
      five patients underwent a Ladd's procedure during an emergency admission. Thirty
      one patients had volvulus or intestinal ischemia, 7 underwent intestinal
      resection, and 1 patient died. Based on case weightings, it was estimated that
      362 older children underwent a Ladd's procedure for symptoms related to
      malrotation in 2000 in the United States (5.3 cases per million population).
      CONCLUSIONS: These findings provide support for performing a Ladd's procedure in
      older children with incidentally found malrotation to prevent the rare but
      potentially devastating complications of this anomaly.

PMID- 15868600
TI  - The effect of phenol on ingrown toenail excision in children.
AB  - PURPOSE: Ingrown toenails in children are a common problem with a high recurrence
      rate. The objective of this retrospective data review was to compare simple
      excision of the nail matrix with excision plus phenol (EPP) application in the
      treatment of ingrown toenails. METHODS: The charts of 69 children who underwent
      surgical treatment of one or more ingrown toenails from 1994 to 2000 were
      reviewed. The primary procedure was noted (excision alone [EA] vs EPP) and dates
      of recurrences and reoperations were recorded. Parents were then surveyed by
      phone regarding complications, cosmetic outcome, and overall satisfaction with
      the procedure. Five scale categories, ranging from "strongly agree" to "strongly
      disagree", were used, with responses of "strongly agree" and "agree" considered
      as a good outcome. Either Student's t test or the chi2 test (P < .05 considered
      significant) was used for analysis. RESULTS: Thirty-one patients (45%) were in
      the EPP group whereas the remaining 38 had EA. Mean length of follow-up was 4.3
      years for the EA group and 2.1 years for the EPP group. There was no difference
      in age at operation or length of follow-up between the 2 groups. Boys were
      predominant in both groups. The survey response rate was 50/69 (73%). The
      recurrence rate of ingrown toenails in the EA group was 42% vs 4% in the EPP
      group (P = .003). There were no significant differences in parental response with
      regard to operative experience (P = .31) and the cosmetic result (P = .13), with
      most of the respondents (78%) indicating a good outcome for both questions.
      CONCLUSIONS: The addition of phenol to the surgical excision of ingrown toenail
      significantly reduced the incidence of recurrence, with similar patient
      satisfaction and an equivalent cosmetic result.

PMID- 15868601
TI  - Effect of ethnicity on disease activity in systemic lupus erythematosus.

PMID- 15868602
TI  - Altitude and giant cell arteritis.

PMID- 15868605
TI  - Response of systemic onset juvenile rheumatoid arthritis to etanercept: is the
      glass half full or half empty?

PMID- 15868606
TI  - Reliability of scoring methods to measure radiographic change in patients with
      rheumatoid arthritis.

PMID- 15868607
TI  - Localized vasculitis and the peripheral nervous system.

PMID- 15868608
TI  - Gout: excess calories, purines, and alcohol intake and beyond. Response to a
      urate-lowering diet.

PMID- 15868609
TI  - Reproducibility and sensitivity to change of 5 methods for scoring hand
      radiographic damage in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To compare intrarater and interrater reproducibility and sensitivity
      to change of 5 scoring methods for radiographic damage on hand radiographs in
      patients with rheumatoid arthritis (RA). METHODS: Radiographs of 22 patients from
      Norway and France with average 2 years' disease duration at baseline and mean 30
      months' followup were assessed by 2 readers according to Larsen, Larsen/Rau,
      Sharp, Sharp/van der Heijde, and Simple Erosion Narrowing Score (SENS) methods.
      Reproducibility at baseline and on progression was assessed using intraclass
      correlation coefficients (ICC) and Bland-Altman graphs. Sensitivity to change was
      compared across methods by computing the country-adjusted standardized response
      means (SRM) ratio. RESULTS: Intrarater reproducibility varied with the reader
      (ICC ranging from 0.90 to 0.97), with Larsen and Larsen/Rau ranking highest.
      Interrater reproducibility was highest with Sharp and Sharp/van der Heijde (ICC
      0.76 to 0.93). Bland-Altman graphs showed a decrease of concordance in cases of
      more severe damage. Sensitivity to change was higher with Sharp and Sharp/van der
      Heijde modified for erosions (SRM ratio 1.44 and 1.70), than with Larsen/Rau and
      SENS. The differences between Sharp, Sharp/van der Heijde, and Larsen were less
      for joint space narrowing. There was a significant reader effect (p < 0.05) in
      all but the Sharp method. Expressed as percentage of the maximum score, the
      smallest detectable difference varied between 3.5% (Sharp/van der Heijde) and
      14.2% (SENS erosion). CONCLUSION: All methods have high intraobserver and
      interobserver reliability. The interrater reproducibility decreases with disease
      severity. Recent modified methods perform best to detect changes, but the
      advantages of SENS seemed to be lost when applied on hand radiographs alone.
      Training the readers appears to be essential.

PMID- 15868610
TI  - Methotrexate suppresses inflammatory agonist induced interleukin 6 synthesis in
      osteoblasts.
AB  - OBJECTIVE: Interleukin 6 (IL-6) is a pleiotropic cytokine that plays a crucial
      role in the pathogenesis of rheumatoid arthritis (RA). In bone metabolism, it is
      known that IL-6 is produced and secreted by osteoblasts, and that IL-6 induces
      osteoclast formation and stimulates bone resorption. Various bone inflammatory
      agonists such as tumor necrosis factor-alpha (TNF-alpha), IL-1alpha,
      prostaglandin D2 (PGD2), PGE2, and PGF2alpha, which play important roles in the
      pathogenesis of RA, induce IL-6 synthesis in osteoblast-like MC3T3-E1 cells. Low
      dose methotrexate (MTX) is currently used for treatment of patients with RA. We
      investigated the effect of MTX on IL-6 synthesis induced by these agents in MC3T3
      E1 cells. METHODS: Cultured cells were pretreated with various doses of MTX, and
      then stimulated by these inflammatory agonists. The IL-6 in the conditioned
      medium was measured by IL-6 enzyme immunoassay. RESULTS: MTX significantly
      suppressed IL-6 synthesis stimulated by these agonists in a dose-dependent
      manner, although MTX alone had no effect on the levels of IL-6. In addition, MTX
      significantly inhibited the enhancement by IL-17 of TNF-alpha-stimulated IL-6
      synthesis. MTX reduced the levels of IL-6 induced by 12-O-tetradecanoylphorbol 13
      acetate, a direct activator of protein kinase C (PKC), suggesting that MTX
      inhibits PKC signals for IL-6 synthesis. CONCLUSION: MTX suppresses IL-6
      synthesis stimulated by various inflammatory agonists in osteoblasts.

PMID- 15868611
TI  - Frequency of remissions in early rheumatoid arthritis defined by 3 sets of
      criteria. a 5-year followup study.
AB  - OBJECTIVE: To study the frequency of remission using 3 sets of criteria in
      patients with rheumatoid arthritis (RA) at 5 years after the diagnosis. METHODS:
      All adult patients with recent onset inflammatory arthritis who did not meet
      criteria or show clinical signs of other specific arthritides were included in
      the RA1997 inception cohort at Jyvaskyla Central Hospital, Finland, and were
      assessed for remission at 5-year control examination. Remission was defined as
      (1) American College of Rheumatology (ACR) remission (fatigue excluded), (2)
      clinical remission with no tender and no swollen joints and normal erythrocyte
      sedimentation rate, and (3) radiographic remission with no worsening of erosions
      and no new erosions from baseline to 5 years. RESULTS: The study included 127
      patients with early RA (mean age 56 yrs, 61% female, 54% with positive rheumatoid
      factor, and 25% with erosions). At 5 years, 111 patients were examined, 17% (95%
      CI 11%-25%) of whom met ACR remission criteria, 37% (95% CI 28%-47%) met clinical
      remission criteria, and 55% (95% CI 49%-68%) met radiographic remission criteria.
      Only 13 (12%) patients met all 3 sets of remission criteria. The rate of
      remission was statistically significantly different (p < 0.001) using the 3 sets.
      CONCLUSION: The rate of remission in RA depends on the criteria used. No gold
      standard exists for defining remission in RA. A set of criteria including no sign
      of inflammatory activity and no radiographic progression might be a basis for
      development of clinically relevant remission criteria for RA.

PMID- 15868612
TI  - Radiological cervical spine involvement in patients with rheumatoid arthritis: a
      cross sectional study.
AB  - OBJECTIVE: To investigate the frequency and the severity of radiological cervical
      spine involvement in patients with rheumatoid arthritis (RA). METHODS: We
      investigated 165 consecutive unselected patients with RA who fulfilled the
      revised American College of Rheumatology criteria for RA. All patients had a
      complete physical and laboratory evaluation. Patients had a radiological
      evaluation that included hand and wrist radiographs, as well as cervical spine
      radiographs in anteroposterior, lateral, and lateral in full flexion views. Hand
      radiographs were evaluated according to the Larsen criteria, while cervical
      radiographs were evaluated according to Winfield classification. RESULTS: There
      were 143 women and 22 men, with a mean age of 59.6 +/- 12.5 and disease duration
      12.3 +/- 13.9 years. Positive rheumatoid factor was found in 63.6% of patients.
      One hundred forty-six patients presented radiological findings related to
      cervical spine involvement: atlantoaxial subluxations were found in 20.6% and
      erosions of the odontoid process in 2.4%; none presented vertical subluxation.
      Subaxial subluxations were found in 43.6%, disc space narrowing at C2-C3, C3-C4,
      C4-C5 levels in 66.1%, and vertebral plate sclerosis and erosions in 43.6%.
      CONCLUSION: Cervical spine radiological involvement is a frequent finding in our
      patients with RA, but the severity of the disease is rather mild, possibly
      related to the ethnic background.

PMID- 15868613
TI  - Survey nonresponse is associated with increased mortality in patients with
      rheumatoid arthritis and in a community population.
AB  - OBJECTIVE: To determine whether nonresponse to a mailed health survey predicts
      mortality in patients with rheumatoid arthritis (RA) and in a community sample in
      Finland. METHODS: A 5-page health questionnaire was administered in 2000. Two
      years later the vital status of the subjects was ascertained from the Population
      Registry. RESULTS: A total of 1095 (73%) patients with RA and 1530 (77%)
      community control subjects returned a completed questionnaire. Over the 2-year
      period, the number of deaths was 57 (5.2%) in RA responders and 37 (9.3%) in RA
      nonresponders (p = 0.004). The corresponding figures in community controls were
      34 (2.2%) and 23 (4.9%) (p = 0.002). In a Cox regression model adjusted for age
      and sex, RA patient and community control nonresponders were respectively 1.65
      (95% CI 1.07 to 2.55) and 2.89 (95% CI 1.69 to 4.94) times more likely to die
      over the 2 years compared to the responders. CONCLUSION: Nonresponders to a
      mailed health survey were more likely to die over 2 years compared to responders.
      The possible nonresponse bias should be kept in mind in the interpretation of the
      results of studies that are based on mail questionnaires only.

PMID- 15868614
TI  - Validation of the Functional Assessment of Chronic Illness Therapy Fatigue Scale
      relative to other instrumentation in patients with rheumatoid arthritis.
AB  - OBJECTIVE: This study validated a brief measure of fatigue in rheumatoid
      arthritis (RA), the Functional Assessment of Chronic Illness Therapy (FACIT)
      Fatigue Scale. METHODS: The FACIT Fatigue was tested along with measures
      previously validated in RA: the Multidimensional Assessment of Fatigue (MAF) and
      Medical Outcomes Study Short-Form 36 (SF-36) Vitality. The sample included 636
      patients with RA enrolled in a 24 week double blind, randomized clinical trial
      (RCT) of adalimumab versus placebo. RESULTS: The FACIT Fatigue showed good
      internal consistency (alpha = 0.86 to 0.87), strong association with SF-36
      Vitality (r = 0.73 to 0.84) and MAF (r = -0.84 to -0.88), and the ability to
      differentiate patients according to clinical change using the American College of
      Rheumatology (ACR) response criteria (ACR 20/50/70). Psychometric performance of
      the FACIT Fatigue scale was comparable to that of the other 2 fatigue measures. A
      minimally important difference in FACIT Fatigue change score of 3-4 points was
      confirmed in a separate sample of 271 patients with RA enrolled in a second
      double blind RCT of adalimumab versus placebo. CONCLUSION: The FACIT Fatigue is a
      brief, valid measure for monitoring this important symptom and its effects on
      patients with RA.

PMID- 15868615
TI  - A comparison of prospective and retrospective evaluations of the Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology Damage Index
      for systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate the comparability of prospective and retrospective
      evaluations of the Systemic Lupus International Collaborating Clinics/American
      College of Rheumatology Damage Index (SLICC/ACR DI). METHODS: Consecutive
      patients meeting ACR criteria for SLE were enrolled prospectively in our cohort.
      Prospective SLICC/ACR DI scores were collected on the 134 cohort members who were
      observed in the cohort between 1993-1999. The last available prospective
      SLICC/ACR DI scores were compared to scores that were retrospectively assigned
      (for the corresponding time point) from chart review by a research nurse blinded
      to the prospective values. Intra- and inter-observer agreement was assessed.
      Kappa coefficients with 95% confidence intervals (CI) were determined. RESULTS:
      The kappa correlation coefficient for agreement between prospective versus
      retrospective total damage scores was 0.68 (95% CI 0.54-0.81). Moderate to very
      good agreement was also observed with respect to the 12 individual organ systems
      itemized in this damage index. Substantial agreement was found between
      assessments done by different research nurses and for repeat assessments done by
      the same research nurse. CONCLUSION: These data suggest good agreement between
      prospective and retrospective evaluations of the SLICC/ACR DI scores.

PMID- 15868616
TI  - Adjusted mean Systemic Lupus Erythematosus Disease Activity Index-2K is a
      predictor of outcome in SLE.
AB  - OBJECTIVE: To test the predictability of the adjusted mean Systemic Lupus
      Erythematosus Disease Activity Index-2K (AMS) for main outcomes in systemic lupus
      erythematosus (SLE), namely presence of damage, coronary artery disease (CAD),
      and avascular necrosis (AVN). METHODS: Included in this study are patients with
      regular followup from the University of Toronto Lupus Clinic. This was defined as
      a minimum of 3 visits and no absence exceeding 18 consecutive months. For each
      visit, AMS was evaluated. The ability of the AMS to predict each of the main
      outcomes was evaluated through time-dependent covariate survival analysis.
      Adjustments to the regression models were made to include other risk factors such
      as sex, age at diagnosis (AGE), SLEDAI-2K at presentation (SLEDAI), disease
      duration (DD), and use of corticosteroids, immunosuppressives (IM), or
      antimalarials (AM). RESULTS: Five hundred and seventy-five patients were included
      covering the period from 1970 to 2002. A total of 325 developed damage, 55 had
      CAD, and 68 had AVN. Presence of damage was not associated with sex, SLEDAI, or
      AM but was significantly associated with AMS, AGE, DD, and use of steroids or IM
      (all p < 0.001). CAD was not associated with SLEDAI or use of steroids or AM but
      with all other variables AMS (p = 0.046), sex (p = 0.009), AGE (p < 0.0001), DD
      (p < 0.0001), and IM (p = 0.035). Predictors of AVN were DD (p = 0.032) and IM (p
      < 0.0001) but not sex, AGE, use of steroids, AM, SLEDAI, or AMS. CONCLUSION: AMS
      is associated with the presence of damage and CAD. It is not associated with AVN.

PMID- 15868617
TI  - Can the urine dipstick test reduce the need for microscopy for assessment of
      systemic lupus erythematosus disease activity?
AB  - OBJECTIVE: Urine microscopic examination is an important component of the
      Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). We investigated
      whether the urine dipstick test can reduce the need for microscopy for the
      assessment of SLEDAI. METHODS: We studied 269 urine samples from 259 SLE patients
      with Albustix and Hemastix reagent strips. The results were compared to
      concomitant microscopic examination of urinary sediment. RESULTS: When trace red
      blood cell was defined as the cutoff, the sensitivity, specificity, and negative
      predictive value (NPV) of the Hemastix urine test were 0.98, 0.53, and 0.99,
      respectively, for hematuria; 0.82, 0.47, and 0.90, respectively, for the presence
      of pyuria; and 0.91, 0.44, and 0.98, respectively, for the presence of casts by
      microscopic examination. When proteinuria of 1+ was defined as the cutoff, the
      sensitivity, specificity, and NPV of the Albustix test were 1.00, 0.46, and 0.99,
      respectively, for urinary casts; and 0.82, 0.49, and 0.90, respectively, for the
      presence of pyuria. When both Albustix and Hemastix were applied as screening
      test, urine microscopy could be reduced by 27%; however, 8% of cases with normal
      Albustix and Hemastix tests had at least one abnormality on urine microscopy
      examination. CONCLUSION: In patients with SLE, a combination of Albustix and
      Hemastix urine tests showed reasonable sensitivity to detect abnormalities in
      urine sediment. Based on these results, routine urine microscopy can be limited
      to SLE patients with abnormal Albustix or Hemastix tests. Rarer causes of
      abnormal renal function in lupus, such as tubulointerstitial nephritis or drug
      induced interstitial nephritis, would be manifested by pyuria and therefore would
      not necessarily be detected by changes in the blood and protein detectors on the
      urine dipstick.

PMID- 15868618
TI  - Responsiveness of the SF-36 and the Health Assessment Questionnaire Disability
      Index in a systemic sclerosis clinical trial.
AB  - OBJECTIVE: This study compares the responsiveness to change of the Medical
      Outcomes Study Short Form Health Survey (SF-36), a measure of health related
      quality of life (HRQOL), and the Health Assessment Questionnaire Disability Index
      (HAQ-DI), a function instrument, in a randomized clinical trial for treatment of
      systemic sclerosis (SSc). METHODS: A phase 2/3, multicenter, prospective, placebo
      controlled trial was conducted to evaluate human recombinant relaxin treatment in
      patients with diffuse SSc over 24 weeks. At baseline, subjects had stable,
      moderately severe, diffuse SSc of disease duration < or = 5 years, modified
      Rodnan skin score > or = 20, serum creatinine < 2.0 mg/dl, percentage forced
      vital capacity (% FVC) predicted > or = 50%, and % DLCO predicted > or = 40% and
      were not receiving concomitant disease modifying therapies. Internal consistency
      reliability of multi-item scales was estimated using Cronbach's alpha.
      Responsiveness to change of the SF-36 and HAQ-DI was computed between Weeks 0 and
      24. Subjects were classified as unchanged or having a meaningful change in 4
      different external measures: Change in (1) skin score > or = 30%; (2) % FVC
      predicted of > or = 15%; (3) self-reported patient global assessment by visual
      analog scale (VAS) > or = 20%; and (4) physician global assessment by VAS of > or
      = 20%. Responsiveness indices were computed and Cohen's effect size criteria were
      used to assess the magnitude of change. RESULTS: A total of 239 patients
      participated in this trial, with 196 completing the 24 week trial. Cronbach's
      alpha for the SF-36 scales ranged from 0.76 to 0.93 and for the HAQ-DI ranged
      from 0.69 to 0.91 (good to excellent). The SF-36 had a larger magnitude of
      responsiveness in overall disease (patient and physician global assessment)
      compared to the HAQ-DI, while the HAQ-DI had a larger magnitude of responsiveness
      in clinical measures (i.e., change in skin score and % FVC predicted) than the SF
      36. CONCLUSION: These data support inclusion of both the SF-36 and HAQ-DI as
      outcome measures in future clinical trials of diffuse SSc.

PMID- 15868619
TI  - Computerized nailfold video capillaroscopy--a new tool for assessment of
      Raynaud's phenomenon.
AB  - OBJECTIVE: To develop a computer based nailfold video capillaroscopy system with
      enhanced image quality and to assess its disease-subgroup resolving power in
      patients with primary and secondary Raynaud's phenomenon (RP). METHODS: Using
      frame registration software, digitized video images from the microscope were
      combined to form a panoramic mosaic of the nailfold. Capillary dimensions (apex,
      arterial, venous, and total width) and density were measured onscreen.
      Significantly, the new system could guarantee analysis of the same set of
      capillaries by 2 observers. Forty-eight healthy control subjects, 21 patients
      with primary RP, 40 patients with limited cutaneous systemic sclerosis (lcSSc),
      and 11 patients with diffuse cutaneous SSc (dcSSc) were studied. Intra- and
      interobserver variability were calculated in a subset of 30 subjects. RESULTS:
      The number of loops/mm was significantly lower, and all 4 capillary dimensions
      significantly greater, in SSc patients versus controls plus primary RP patients
      (p < 0.001 for all measures). When comparing control (+ primary RP) patients with
      SSc patients (lcSSc + dcSSc) the most powerful discriminator was found to be the
      number of loops/mm. Results for intra- and interobserver reproducibility showed
      that the limits of agreement were closer when both observers measured the same
      capillaries. CONCLUSION: The key feature of the newly developed system is that it
      improves reproducibility of nailfold capillary measurements by allowing
      reidentification of the same capillaries by different observers. By allowing
      access to previous measurements, the new system should improve reliability in
      longitudinal studies, and therefore has the potential of being a valuable outcome
      measure of microvessel disease/involvement in clinical trials of scleroderma
      spectrum disorders.

PMID- 15868620
TI  - Neutrophil CD64 expression in Behcet's disease.
AB  - OBJECTIVE: Hyperfunction of neutrophils is a characteristic finding in Behcet's
      disease (BD). Microbial agents have been proposed as causative agents in the
      disease flares. Fc gamma receptor 1 (CD64) is not normally expressed by
      neutrophils of healthy individuals, but is upregulated by these cells in response
      to microbial wall components and proinflammatory cytokines. The degree of
      polymorphonuclear leukocyte (PMN) CD64 expression is different in autoimmune
      diseases and systemic infectious diseases. We investigated PMN CD64 expression in
      patients with BD. METHODS: Thirty-seven patients with active BD (M/F: 18/19, mean
      age: 34.4 +/- 9.7 yrs), 35 patients with inactive BD (M/F: 11/24, mean age: 35.9
      +/- 11.6 yrs), 27 patients with culture proven infections (M/F: 19/8, mean age:
      54.4 +/- 15.2 yrs), 31 healthy controls (M/F: 14/17, mean age: 37.7 +/- 8.7 yrs),
      and 42 patients with active inflammatory disease (M/F: 13/29, mean age: 39.3 +/-
      14.9 yrs) were enrolled in this study. Flow cytometry was used to assess the
      prevalence of CD64-bearing PMN in whole blood samples. RESULTS: The prevalence of
      CD64-bearing PMN was significantly higher in patients with infectious disease
      (77.1 +/- 18.4), inflammatory disease (37.1 +/- 27.5), and active BD (48.9 +/-
      22.5) than in healthy controls (9.5 +/- 7.8) or patients with inactive BD (12.9
      +/- 9.5). CD64 expression was similar in controls and patients with inactive BD.
      In the infectious disease group, expression of CD64 was significantly higher than
      in the active BD and active inflammatory disease groups, while there was no
      significant difference between the groups of patients with active BD and
      inflammatory disorders. CONCLUSION: Neutrophil CD64 expression increases during
      exacerbation of BD. This increase appears to be a non-specific inflammatory
      response and does not reflect PMN activation triggered by a living microorganism.

PMID- 15868621
TI  - Nonsystemic vasculitic neuropathy: a clinicopathological study of 22 cases.
AB  - OBJECTIVE: The involvement of the peripheral nervous system in patients with
      systemic vasculitis has been reported, but nonsystemic peripheral nervous system
      vasculitis is not so well known. We investigated the clinical,
      electrophysiological, and pathological features of nonsystemic vasculitic
      neuropathy (NSVN) in order to establish the clinical and histological
      manifestations and to promote the earlier diagnosis of the syndrome. METHODS:
      Biopsies were selected from over 700 sural nerve biopsies performed at the
      Section of Neuropathology, Neurological Clinic of Athens University Hospital. The
      diagnosis of vasculitis was based on established clinicopathological criteria.
      Other causes of peripheral neuropathy were excluded. Complete laboratory,
      clinical, electrophysiological, and pathological studies were performed in all
      cases. RESULTS: Nerve biopsies of 22 patients were diagnosed as NSVN. The
      pathological features were vasculitis and predominant axonal degeneration with a
      varying pattern of myelinated fiber loss. The vasculitic changes were found
      mainly in small epineural blood vessels. Mononeuritis multiplex and distal
      symmetrical sensorimotor neuropathy were equally frequent. CONCLUSION: NSVN
      should be suspected in a case of unexplained polyneuropathy without evidence of
      systemic involvement. Clinical and neurophysiological studies are essential for
      the detection of nerve involvement, but the specific diagnosis of NSVN may be
      missed unless a biopsy is performed.

PMID- 15868622
TI  - Arthritis as the sole episodic manifestation of familial Mediterranean fever.
AB  - OBJECTIVE: To clinically and genetically characterize patients with familial
      Mediterranean fever (FMF) in whom arthritis constitutes the only manifestation,
      and to establish the most important features distinguishing FMF arthritis in such
      a setting from other forms of mono/oligo arthritides. METHODS: The study
      population comprised 14 patients with episodes of arthritis as the only
      manifestation of FMF who nevertheless fulfilled the diagnostic criteria for FMF.
      The control group consisted of 28 patients with episodic mono/oligo arthritis of
      different disease entities (palindromic, reactive, inflammatory bowel disease,
      Reiter's, seronegative spondyloarthropathy, chronic juvenile, Behcet's, and gouty
      arthritis) who presented to the rheumatology clinic during the study period.
      Patients in both groups underwent clinical evaluation and donated blood for FMF
      gene analysis. RESULTS: The study and control groups shared similar age and sex
      distribution and experienced the monoarthritic attacks at similar sites, usually
      the knee and ankle joint. The 2 groups differed significantly in features of
      arthritis (which were febrile and of short duration in FMF), family history of
      FMF, mutation analysis, and response to colchicine. These differences allowed the
      defining of a rule, which readily distinguishes FMF arthritis from other forms of
      episodic mono/oligo arthritis. CONCLUSION: The clinical, ethnic, and genetic
      features of recurrent monoarthritis of FMF are specific and may separate FMF from
      other entities with mono/oligo arthritis.

PMID- 15868623
TI  - Vertebral fracture and bone mineral density in women receiving high dose
      glucocorticoids for treatment of autoimmune diseases.
AB  - OBJECTIVE: To evaluate the factors influencing the occurrence of vertebral
      fracture in patients receiving high dose glucocorticoids (GC). METHODS: A cross
      sectional study was performed on women who had received at least 0.5 mg/kg of
      oral glucocorticoid for the treatment of autoimmune diseases for more than 1
      month between 1998 and 2003. Logistic regression analysis and chi-square test
      were used to examine the effects of glucocorticoid dose and other factors on
      vertebral fractures. Receiver-operating characteristics curve (ROC) analysis was
      used to determine the bone mineral density (BMD) cutoff value for the risk of
      vertebral fracture. RESULTS: The study population comprised 160 women, including
      35 with vertebral fractures. In ROC analysis, the BMD threshold of the risk of
      fracture for postmenopausal women (0.787 g/cm2 , T score -2.1) was lower than
      that for premenopausal women (0.843 g/cm2 , T score -1.7). Among patients with
      fractures, 7 of 16 premenopausal patients had normal BMD values (T score > -1),
      whereas only one of 19 postmenopausal patients showed a comparable level of BMD.
      Additionally, vertebral fracture was more frequent for patients with high total
      cholesterol values (> 280 mg/dl) than for those with normal total cholesterol
      values (< 220 mg/dl). Moreover, patients with high total cholesterol values had
      lower BMD values than those with normal total cholesterol values. CONCLUSION: The
      fact that vertebral fracture frequently occurred in premenopausal patients with
      normal BMD and evidence that hyperlipidemia correlated with fracture suggest the
      pathology of vertebral fracture secondary to high dose glucocorticoid therapy is
      multifactorial and possibly involves lipid metabolism.

PMID- 15868624
TI  - Racial disparities in the receipt of osteoporosis related healthcare among
      community-dwelling older women with arthritis and previous fracture.
AB  - OBJECTIVE: To examine potential racial/ethnic disparities in osteoporosis care
      among community-dwelling older women with self-reported arthritis and previous
      fracture. METHODS: We conducted a computer assisted telephone interview using a
      population based random sample drawn from 6 counties in Alabama, USA. Eligible
      respondents had self-reported arthritis and were over 50 years of age; 1424
      people responded to the survey. Logistic regression was used to examine the
      association of race/ethnicity with the receipt of dual energy x-ray
      absorptiometry (DEXA) and prescription osteoporosis treatments (including
      bisphosphonates, calcitonin, hormone replacement, or selective estrogen receptor
      modulators) among older women with a history of fracture. RESULTS: Of eligible
      African American and Caucasian female respondents, 251 (25%) reported a history
      of fracture after 45 years of age. Women with a history of self-reported fracture
      were predominantly Caucasian (n = 178, 71%) and had a mean age of 68 +/- 11
      years. After multivariable adjustment, African American women with a fracture
      history were less likely than Caucasian women with a history of fracture to
      receive a DEXA (OR 0.39, 95% CI 0.19-0.81) or prescription osteoporosis medicines
      (OR 0.17, 95% CI 0.08-0.37). CONCLUSION: In this population of community-dwelling
      older women, African American respondents at high risk for fracture were far less
      likely than Caucasians to receive osteoporosis related healthcare.

PMID- 15868625
TI  - Increased type II collagen degradation and very early focal cartilage
      degeneration is associated with upregulation of chondrocyte differentiation
      related genes in early human articular cartilage lesions.
AB  - OBJECTIVE: Articular cartilage degeneration in osteoarthritis (OA) involves
      excessive degradation of extracellular matrix (ECM) and chondrocyte
      differentiation (hypertrophy). We determined the interrelationship between the
      extent of collagen cleavage by collagenase, cartilage degeneration, and
      differentiation related gene expression in patella-femoral condylar cartilages of
      patients bearing very early focal OA-like articular cartilage lesions. METHODS:
      Articular cartilage specimens with very early focal lesions and adjacent normal
      cartilage from 3 donors were removed at autopsy as full-depth slices cut from the
      femoral condyle surface that articulates with patella. Slices were divided into
      sections and used for Mankin grading, examination of collagenase cleavage of type
      II collagen by ELISA, and gene expression by RT-PCR. RESULTS: Early focal
      cartilage degeneration was associated with increased collagenase cleavage of type
      II collagen. The collagenases metalloproteinase-1 (MMP-1), MMP-14 (MT1-MMP), and
      aggrecanase ADAMTS-5 (a disintegrin and metalloprotease with thrombospondin
      motifs) (but not ADAMTS-4); cytokines interleukin 1alpha/beta and tumor necrosis
      factor-alpha (TNF-alpha); chondrocyte terminal differentiation-related genes
      COL10A1, MMP-13, MMP-9, Indian hedgehog; and caspase 3 were often upregulated in
      the vicinity of the lesion. Growth factors associated with growth plate
      chondrocyte proliferation, namely fibroblast growth factor-2, parathyroid hormone
      related protein, transforming growth factor (TGF)-beta1/2, as well as the matrix
      molecules COL2A1 and aggrecan were expressed adjacent to and remote from the
      lesion. Of all genes only caspase 3 and ADAMTS-5 expression was exclusively seen
      in association with these early lesions. Elevation of collagenase activity was
      associated with a frequent elevation of expression of COL10A1, caspase 3, IL
      1alpha/beta, MMP-1, and ADAMTS-5, and a decreased expression of Sox-9 (SRY-type
      high-mobility-group box transcription factor-9), TGF-beta1, TGF-beta2, TNF-alpha,
      and aggrecan. Other genes showed no observable difference with changes in
      collagenase activity. CONCLUSION: Very early focal degeneration in knee articular
      cartilage is accompanied by upregulation of collagenase activity and expression
      of genes associated with chondrocyte terminal differentiation and matrix
      degradation. Thus chondrocyte differentiation may be closely related to the very
      early development of cartilage degeneration such as occurs in OA.

PMID- 15868626
TI  - Expression and regulation of microsomal prostaglandin E synthase-1 in human
      osteoarthritic cartilage and chondrocytes.
AB  - OBJECTIVE: Elevated production of prostaglandin E2 (PGE2) plays an important role
      in the pathogenesis of arthritis. Recently, an inducible microsomal prostaglandin
      E synthase-1 (mPGES-1) was identified. This enzyme is functionally coupled with
      cyclooxygenase-2 (COX-2) and converts the COX product PGH2 to PGE2. We analyzed
      expression of mPGES-1 in human normal and osteoarthritic (OA) cartilage and
      determined the effect of different inflammatory agonists on the expression of
      mPGES-1 in OA chondrocytes. METHODS: Expression of mPGES-1 mRNA and protein in
      cartilage was determined by quantitative real-time reverse transcriptase
      polymerase chain reaction and immunohistochemistry, respectively. OA chondrocytes
      were treated with different inflammatory agents, and mPGES-1 protein expression
      was evaluated by Western blot. Activation of the mPGES-1 promoter was assessed in
      transient transfection experiments. RESULTS: Levels of mPGES-1 mRNA and protein
      were markedly elevated in OA versus normal cartilage. Treatment of chondrocytes
      with interleukin 1beta (IL-1beta) induced expression of mPGES-1 protein in a dose
      and time-dependent manner. This appears to occur at the transcriptional level,
      as IL-1beta induced expression of mPGES-1 mRNA and the activity of this gene
      promoter. Tumor necrosis factor-alpha (TNF-alpha) and IL-17 also upregulated
      expression of mPGES-1 protein and displayed a synergistic effect with IL-1beta.
      Peroxisome proliferator-activated receptor-gamma ligands, 15-deoxy-delta(12,14)
      prostaglandin J2 and troglitazone, inhibited IL-1beta-induced mPGES-1 protein
      expression, an effect that was reversed by exogenous PGE2. CONCLUSION: Our study
      shows that mPGES-1 expression is upregulated in OA versus normal cartilage and
      that proinflammatory cytokines increased mPGES-1 expression in chondrocytes.
      These data suggest that mPGES-1 may prove to be an interesting therapeutic target
      for controlling PGE2 synthesis.

PMID- 15868627
TI  - Glucosamine sulfate and cartilage type II collagen degradation in patients with
      knee osteoarthritis: randomized discontinuation trial results employing
      biomarkers.
AB  - OBJECTIVE: To determine whether glucosamine sulfate has an effect on cartilage
      type II collagen degradation in patients with knee osteoarthritis (OA). METHODS:
      A randomized, double blind, placebo controlled glucosamine discontinuation trial
      was conducted in 137 subjects with knee OA, who had had at least moderate relief
      of knee pain after starting glucosamine. Subjects were randomized to glucosamine
      at prestudy dose or placebo at an equivalent dose. Treatment was continued to
      Week 24 or disease flare, whichever occurred first. Serum and urine samples were
      collected at Weeks 0, 4, 12, and 24 or flare visit. Samples were analyzed in
      triplicate for 2 type II collagen degradation biomarkers: C2C epitope (COL2
      3/4C(long)) and C1,2C epitope (COL2-3/4C(short)). The primary outcome was the
      mean change in serum and urine C1,2C/C2C ratio in the glucosamine and placebo
      groups from baseline to final (flare or Week 24) visit. Linear regression
      analyses were conducted to adjust for potential confounders. Due to non-normal
      distributions, the data were log-transformed (lnC1,2C/C2C). Secondary outcomes
      included comparison of mean change scores at final visit compared to baseline for
      serum and urine C1,2C and C2C in the 2 treatment groups and in Flare versus No
      Flare groups. RESULTS: Baseline and final visit samples were available in 130
      subjects for serum analysis and 126 subjects for urinalysis. No significant
      difference was seen between placebo and glucosamine groups in the serum C1,2C/C2C
      ratio, with a mean (SD) change from baseline to final visit of 0.8 (27.8) and 
      0.1 (1.8), respectively (mean difference 0.9; 95% CI -6.0, 7.7, p = 0.80).
      Similarly, no differences between treatment groups were seen for mean change in
      urine C1,2C/C2C (p = 0.82), or for mean change in C2C or C1,2C. In linear
      regression analysis, after adjustment for sex, radiographic severity, baseline
      lnC1,2C/C2C ratio, WOMAC function, and flare status, treatment was not a
      significant predictor of final serum or urine lnC1,2C/C2C ratio. When those who
      experienced flare were contrasted with those without flare, there was a
      nonsignificant trend toward a difference in mean baseline to final visit change
      score for serum C1,2C/C2C ratio (p = 0.12). In addition, in the multivariable
      linear regression analysis, flare status showed a borderline association with
      final visit serum lnC1,2C/C2C ratio (p = 0.16). CONCLUSION: No statistically
      significant effect of glucosamine sulfate on type II collagen fragment levels in
      serum or urine was observed for knee OA over 6 months. Further research is
      necessary to elucidate which biopathologic systems, if any, are affected by
      glucosamine treatment. While collagen degradation products may be of value in
      predicting progression, at least as defined by clinical flare, a larger dataset
      would be needed to prove this.

PMID- 15868628
TI  - Response to a urate-lowering diet according to polymorphisms in the
      apolipoprotein AI-CIII-AIV cluster.
AB  - OBJECTIVE: The apolipoprotein AI-CIII-AIV cluster has been associated with the
      response to a urate-lowering diet, and polymorphisms in the apolipoprotein CIII
      gene have been associated with hyperuricemia and hypertriglyceridemia. We
      assessed the influence of polymorphisms in the apolipoprotein AI-CIII-AIV cluster
      on the response to a urate-lowering diet in patients with hyperuricemia. METHODS:
      A urate-lowering diet was followed for 2 weeks by 64 men with hyperuricemia.
      Plasma concentrations of triglycerides, cholesterol, glucose, and uric acid, and
      the uric acid clearance and 24-hour uric acid urinary excretory fraction were
      measured before and after the diet. The data were analyzed in association with
      the polymorphisms of the apolipoprotein AI-CIII-AIV gene cluster. RESULTS: After
      the urate-lowering diet, the plasma levels of triglycerides, cholesterol,
      glucose, and uric acid and 24-hour uric acid excretion all fell significantly.
      Paired sample ANOVA showed that the decrease was mainly due to the diet, except
      for the plasma triglycerides, which were influenced by allele X2 of the XmnI
      polymorphism of the apolipoprotein AI gene. CONCLUSION: The response of the
      biological variables to a urate-lowering diet was mainly influenced by diet.
      Changes in triglycerides were also influenced by the apolipoprotein AI XmnI
      polymorphism (p = 0.04), suggesting a gene-diet interaction (p = 0.03).

PMID- 15868629
TI  - Serum uric acid concentration as a risk factor for cardiovascular mortality: a
      longterm cohort study of atomic bomb survivors.
AB  - OBJECTIVE: To elucidate the association of serum uric acid concentration with
      cardiovascular mortality risk. METHODS: Serum uric acid level measured from 1966
      through 1970 in 10,615 Japanese individuals from a cohort of atomic bomb
      survivors was analyzed for association with subsequent cardiovascular and all
      cause mortality until 1999 using the Cox proportional hazard model. RESULTS:
      During an average followup of 24.9 years, 5225 deaths occurred, of which 1984
      were ascribed to cardiovascular disease. In men, after adjustment for age,
      elevated serum uric acid level was associated with both cardiovascular and all
      cause mortality. After additional adjustment for potential cardiovascular disease
      risk factors including body mass index, smoking status, alcohol consumption,
      systolic blood pressure, cholesterol level, and histories of hypertension,
      diabetes and cardiovascular disease, elevated serum uric acid level in men was
      associated with all-cause mortality but not with cardiovascular mortality. In
      women, even after these adjustments, elevated serum uric acid level was
      significantly associated with cardiovascular and all-cause mortality. CONCLUSION:
      Increased serum uric acid level is a significant and independent risk factor for
      cardiovascular mortality in women and for all-cause mortality in both men and
      women.

PMID- 15868630
TI  - Determinants of treatment adherence in ethnically diverse, economically
      disadvantaged patients with rheumatic disease.
AB  - OBJECTIVE: To explore the determinants of adherence to medical recommendations,
      including drug therapy and appointment-keeping, among ethnically diverse and
      economically disadvantaged patients with rheumatoid arthritis (RA) and systemic
      lupus erythematosus (SLE). METHODS: Patients with RA and SLE were identified
      through chart review and were invited to participate in focus groups to examine
      their attitudes and beliefs regarding adherence to treatment and medical
      appointments. Eight focus groups (4 RA, 4 SLE) were conducted, with a total of 40
      participants (22 SLE patients and 18 RA patients). Transcripts were analyzed
      using grounded theory techniques and qualitative analysis software to facilitate
      coding interpretation. RESULTS: The majority of participants reported
      experiencing difficulty in adhering to their treatment at least occasionally.
      Both SLE and RA patients reported similar barriers to treatment adherence: fear
      of side effects, financial problems, difficulty in navigating the public health
      system, and perceived treatment inefficacy. RA and SLE patients also revealed
      barriers to appointment keeping, including difficulties in scheduling, financial
      costs, transportation, and functional impairment limiting their ability to attend
      the clinic. CONCLUSION: Patients' perceptions of and experiences with the health
      system, physicians, medication effectiveness, and side effects influence their
      adherence to treatment and other medical recommendations. Strategies to improve
      adherence could include the following: attempting to modify patients' beliefs and
      perceptions regarding medication effectiveness, promoting realistic expectations
      about risk/benefit ratios, and improving access to health care by reducing
      barriers that limit the interaction between patients and the health system.

PMID- 15868631
TI  - Risk factors associated with rheumatic complaints: a WHO-ILAR COPCORD study in
      Shantou, Southeast China.
AB  - OBJECTIVE: To validate the differences of the prevalence of rheumatic symptoms
      between the north and south part of China and to investigate the associated risk
      factors for rheumatic complaints in Shantou, China. METHODS: Four samples
      together comprising 10,638 people > or = 16 years of age were surveyed in 1987,
      1992, 1995, and 1999. The protocol of the ILAR-China Collaborative Study or the
      WHO-ILAR COPCORD Core Questionnaire was implemented. Data on rheumatic symptoms
      that were part of these surveys were collected and analyzed. RESULTS: The
      prevalence rate of rheumatic complaints was increasing in the Shantou area during
      the recent decade (in 1987 11.6%, 1992 12.5%, 1995 16.0%, and 1999 19.8%).
      However, it was still lower than the rate in Beijing, China, in 1987 (40.0%).
      Rheumatic symptoms were more prevalent in women than in men, and were more
      frequently seen in the elderly than in young people. The most frequently involved
      site was the low back followed by the knee and neck. Lumbar pain was more
      frequent among rural residents, while neck pain was more prevalent in the urban
      school-age population group. The prevalence of knee pain was significantly higher
      in people living in multi-story buildings without elevators compared with those
      living in single-story houses. The peak value of bone mineral density (BMD) in
      the Shantou population was 0.839 +/- 0.085 g/cm2 in men, and 0.723 +/- 0.064
      g/cm2 in women, significantly higher than that reported in 13 other provinces and
      cities of China including Beijing. The sense of seeking a physician's care was
      higher in the population with a higher prevalence of rheumatic symptoms than that
      in the group with a lower prevalence of complaints. However, no significant
      difference was found in the rate of disability among the different population
      samples. CONCLUSION: The prevalence rate of rheumatic complaints was lower in
      Shantou than in Beijing. Socioeconomic status, environmental differences (e.g.,
      Shantou in the southern and Beijing in the northern part of China), sex, age,
      occupation, ergonomics, BMD, and awareness of seeking medical care might all be
      risk factors associated with the prevalence of rheumatic complaints.

PMID- 15868632
TI  - Longterm outcomes in patients with giant aneurysms secondary to Kawasaki disease.
AB  - OBJECTIVE: Kawasaki disease (KD) has potentially serious cardiac complications
      including coronary artery aneurysms. Children who develop giant aneurysms (GA)
      are at increased risk of thrombosis and ischemia, and although longterm oral
      anticoagulation with warfarin is recommended, its efficacy has not been studied.
      We examined the longterm outcome of patients with GA secondary to KD, to
      determine if anticoagulation with warfarin aids in the prevention of myocardial
      ischemia. METHODS: We studied patients with KD followed between May 1990 and
      April 2000. RESULTS: Thirty-nine GA occurred in 2.2% of patients with KD (22/997
      patients), and 33 non-GA were also identified in these patients. Patients were
      divided into 2 groups, those taking warfarin and no warfarin. Most patients in
      both groups were also taking antiplatelet agents. The demographics of the 2
      groups were statistically similar, except the median duration of followup was
      significantly longer for patients in the no-warfarin group (6.9 vs 13.3 yrs; p =
      0.008). Four early ischemic events (< 1 year after KD diagnosis) occurred (3
      myocardial infarctions and one stroke). Screening for late ischemic events by
      stress nuclear medicine myocardial perfusion imaging revealed only one patient,
      in the no-warfarin group, with reversible perfusion defects. No patient had
      clinical signs or symptoms of late myocardial ischemia. Echocardiographic
      regression of aneurysms was observed in both groups. In the warfarin vs no
      warfarin group, the diameters of the GA regressed a median 22% vs 32% (p = 0.27),
      and non-GA regressed a median of 30% vs 25% (p = 0.61). Compliance with
      anticoagulation was good, and no major bleeding complication of anticoagulation
      occurred. CONCLUSION: Regression of GA occurred in most of our patients, and
      minimal late ischemia was observed. Further studies are required to evaluate the
      use of oral anticoagulation in patients with GA secondary to KD.

PMID- 15868633
TI  - Etanercept treatment in patients with refractory systemic onset juvenile
      rheumatoid arthritis.
AB  - OBJECTIVE: . To assess the efficacy and safety of etanercept in a large cohort of
      children with refractory systemic onset juvenile rheumatoid arthritis (SOJRA).
      METHODS: Standardized questionnaires were sent to US pediatric rheumatologists
      about patients with SOJRA treated with etanercept. Data were collected at
      baseline and at the last visit on etanercept. Response to treatment was assessed
      and compared to baseline as the mean percentage reduction in the following: acute
      phase reactants, prednisone dose, active joint count, and physician global
      assessment of disease activity. Response was defined as poor if the mean
      reduction was < 30%, fair if 30% to < 50%, good if 50% to < 70%, and excellent if
      > 70%. RESULTS: We analyzed data obtained by survey of 82 SOJRA patients treated
      with etanercept for a mean of 25 months. Poor response to treatment was observed
      in 45% of the children, fair response in 9%, good in 13%, and excellent in 33%.
      Baseline steroid therapy could be discontinued in 27/59 (46%) patients. One or
      more disease flares occurred in 45% of all patients. Twenty-nine patients (35%)
      discontinued therapy, mostly due to lack of response or flare. There were 32
      adverse event reports, most not considered serious, except for 2 cases of
      macrophage activation syndrome. CONCLUSION: In this cohort of children with
      SOJRA, 46% had a good or excellent response, and most were able to reduce
      concomitant corticosteroid doses. The response to etanercept was fair or poor in
      more than half our study population, and disease flares were common. Due to the
      unique cytokine profile of SOJRA, tumor necrosis factor blockade may not be the
      optimal therapeutic approach for children with treatment-resistant SOJRA.

PMID- 15868634
TI  - Efficacy of custom foot orthotics in improving pain and functional status in
      children with juvenile idiopathic arthritis: a randomized trial.
AB  - OBJECTIVE: . To compare the clinical efficacy of custom foot orthotics,
      prefabricated "off-the-shelf" shoe inserts, and supportive athletic shoes worn
      alone, on reducing pain and improving function for children with juvenile
      idiopathic arthritis (JIA). METHODS: Children with JIA and foot pain (n = 40)
      were randomized to one of 3 groups receiving: (1) custom-made semirigid foot
      orthotics with shock absorbing posts (n = 15), (2) off-the-shelf flat neoprene
      shoe inserts (n = 12), or (3) supportive athletic shoes with a medial
      longitudinal arch support and shock absorbing soles worn alone (n = 13). Foot
      pain and functional limitations were measured using the Pediatric Pain
      Questionnaire-visual analog scale (VAS), Timed Walking, Foot Function Index
      (FFI), and the Physical Functioning Subscale of the Pediatric Quality of Life
      Inventory (PedsQL). Measures were administered by personnel blinded to group
      status at baseline (before wearing the assigned intervention) and at 3 months'
      followup. RESULTS: Children in the orthotics group showed significantly greater
      improvements in overall pain (p = 0.009), speed of ambulation (p = 0.013),
      activity limitations (p = 0.002), foot pain (p = 0.019), and level of disability
      (p = 0.024) when compared with the other 2 groups. Both children and parents in
      the orthotics group reported clinically meaningful improvement in child health
      related quality of life, although the group by time interaction did not show
      statistical significance. Except for a reduction in pain for supportive athletic
      shoes (paired t test, p = 0.011), neither the off-the-shelf shoe inserts nor the
      supportive athletic shoes worn alone showed significant effect on any of the
      evaluation measures. CONCLUSION: In children with JIA, custom-made semirigid foot
      orthotics with shock-absorbing posts significantly improve pain, speed of
      ambulation, and self-rated activity and functional ability levels compared with
      prefabricated off-the-shelf shoe inserts or supportive athletic shoes worn alone.

PMID- 15868635
TI  - Rosai-Dorfman disease in a patient with systemic lupus erythematosus.
AB  - Rosai-Dorfman disease (RDD), also known as sinus histocytosis with massive
      lymphadenopathy, is a clinically benign, frequently chronic, painless
      lymphadenopathy. It can also involve extranodal sites. We describe a 37-year-old
      man with a recent diagnosis of systemic lupus erythematosus and antiphospholipid
      antibody syndrome who had lacrimal gland and orbital involvement and nodal and
      extranodal sites with RDD.

PMID- 15868636
TI  - Relapsing polychondritis with aortitis without valvular involvement.
AB  - Relapsing polychondritis is a multisystemic disease of unknown etiology that
      mainly involves the cartilaginous portions of the ear, nose, and trachea.
      Occasionally, there is involvement of the cardiovascular system, which usually
      results in severe morbidity and mortality. The most common manifestation of
      cardiovascular involvement is aortic root dilation resulting in aortic
      regurgitation. We describe the first case in Korea, a 51-year-old woman with
      relapsing polychondritis with aortitis, but without aortic valve involvement. She
      presented only with complaints of abdominal pain, and was successfully treated
      with corticosteroids and methotrexate.

PMID- 15868637
TI  - Retroperitoneal fibrosis secondary to spondylodiscitis after infection with
      Prevotella.
AB  - We report a case of severe retroperitoneal fibrosis (RPF) secondary to lumbar
      spondylodiscitis caused by infection with Prevotella resolving after antibiotic
      therapy. Infection is an unusual cause of RPF, and infection in such cases with
      this anaerobic bacterium has never been described.

PMID- 15868638
TI  - Unusual imaging manifestations of intraosseous tophaceous gout of the patella.

PMID- 15868639
TI  - New drug released for alcohol dependency.

PMID- 15868640
TI  - Ten gotta-have foods. Eating for good health.

PMID- 15868641
TI  - Role of radiotherapy in primary CD30+ and plemorphic small/medium-sized T-cell
      lymphomas.

PMID- 15868642
TI  - Once-weekly fluconazole in children with tinea capitis due to Microsporum canis.

PMID- 15868643
TI  - Dermatofibroma-like atypical granular cell tumour.

PMID- 15868644
TI  - Melasma on the nape of the neck in a man.

PMID- 15868645
TI  - Disturbance in the well-being of a patient with acne: suggestions for
      anticipation and detection.

PMID- 15868646
TI  - Successful rituximab treatment of severe pemphigus vulgaris resistant to multiple
      immunosuppressants.

PMID- 15868647
TI  - Demodicidosis of the nipple.

PMID- 15868648
TI  - Detection of human papillomavirus type 16 in Bowen's disease of the web-space of
      the foot.

PMID- 15868649
TI  - A case of idiopathic calcinosis universalis.

PMID- 15868650
TI  - Abstracts of the 46th Annual Meeting of the Japanese Society of Plant
      Physiologists. March 24-26, 2005, Niigata, Japan.

PMID- 15868651
TI  - Abstracts of the American College of Obstetricians and Gynecologists 53rd Annual
      Clinical Meeting. May 7-11, 2005, San Francisco, California, USA.

PMID- 15868652
TI  - Coffee consumption reduces the risk of hepatocellular carcinoma independently of
      its aetiology: a case-control study.
AB  - BACKGROUND/AIMS: The role of coffee in the development of hepatocellular
      carcinoma (HCC) is debated. The aim of this study was to investigate the role of
      coffee in HCC, taking the main risk factors into account. METHODS: A hospital
      based case-control study was conducted in an area of northern Italy. We recruited
      250 HCC cases and 500 controls hospitalized for any reasons other than neoplasms,
      and liver and alcohol-related diseases. Subjects were interviewed on their
      lifetime history of coffee consumption using a standardized questionnaire.
      RESULTS: Coffee consumption in the decade before the interview was associated
      with a decreasing risk of HCC with a clear dose-effect relation. With respect to
      non-drinking subjects, the odds ratios (ORs) were: 0.8, (95% CI 0.4-1.3) for 1-2
      cups/day, 0.4 (95% CI 0.2-0.8) for 3-4 cups/day and 0.3 (95% CI 0.1-0.7) for 5 or
      more cups/day. The ORs for HCC decreased for drinking >2, compared to 0-2
      cups/day of coffee, for an alcohol intake >80 g/day (OR from 5.7 to 3.3), for
      presence of hepatitis B virus infection (OR from 16.4 to 7.3) or hepatitis C
      virus infection (OR from 38.2 to 9.0). CONCLUSIONS: Coffee drinking was inversely
      associated with HCC regardless of its aetiology.

PMID- 15868653
TI  - Treatment of hepatocellular carcinoma in compensated cirrhosis with radio
      frequency thermal ablation (RFTA): a prospective study.
AB  - BACKGROUND/AIMS: To assess the effectiveness and the safety of radio-frequency
      thermal ablation (RFTA) in patients with hepatocellular carcinoma (HCC) < or = 5
      cm in compensated cirrhosis. METHODS: A cohort of 202 consecutive patients (165
      Child-Pugh class A and 37 class B) was prospectively assessed. A single lesion
      was observed in 160/202 (79.2%), two lesions in 29/202 (14.3%), and three lesions
      in 13/202 (6.4%) of patients. RESULTS: Sixty-seven patients died. Survival rates
      were 80% at 12 months, 67% at 24 months and 57% at 30 months (Child-Pugh A 59%
      and Child-Pugh B 48%). By Cox regression analysis, survival was independently
      predicted by serum albumin levels > or = 35 g/L, platelet count > or =
      100.000/mmc, tumor size < or = 3 cm, complete response at 1 month and Barcelona
      Clinic Liver Cancer (BCLC) staging classification. Overall recurrence rates were
      22, 38, and 44% at 12, 24, and 30 months, respectively. One procedure-related
      death occurred. The proportion of major complications after treatment was 3.9%.
      CONCLUSIONS: A complete response after RFTA significantly increases survival. The
      longest survival is obtained in the presence of HCC < or = 3 cm and of higher
      baseline albumin levels and platelet counts. BCLC staging classification is able
      to discriminate patients with good or poor prognosis.

PMID- 15868654
TI  - Georgeanna Seegar Jones.

PMID- 15868655
TI  - Effects of D-003, a mixture of very long chain fatty acids purified from sugar
      cane wax, at 5 and 10 mg/day on platelet aggregation in healthy volunteers.
AB  - D-003 is a mixture of high molecular weight aliphatic primary acids purified from
      sugar cane wax with antiplatelet and cholesterol-lowering effects. Previous
      studies showed that D-003 (10-20 mg/day) administered for a short time inhibits
      platelet aggregation, 14 days being the longest duration investigated. This study
      was conducted to investigate the effects of D-003 (5 and 10 mg/day) for 30 days
      on platelet aggregation in normocholesterolemic subjects. This report shows the
      effects of D-003 on platelet aggregation to arachidonic acid (AA) (1.5 mM),
      collagen (2 microg/ml) and adenosine 5'-diphosphate ADP (2 microM) assessed at
      baseline and at treatment completion. Fifty-four subjects were randomized to
      placebo or D-003 (5 or 10 mg/day) for 30 days. Platelet aggregation to AA,
      collagen and ADP were assessed. D-003 at the lowest dose (5 mg/day) significantly
      but modestly inhibited (p < 0.01) platelet aggregation to AA (5.0%) and (p <
      0.01) to collagen (7.5%). D-003 at 10 mg/day inhibited (p < 0.001) platelet
      aggregation to AA and collagen (p < 0.01) by 20.3% and 14.7%, respectively. ADP
      induced aggregation, however, was unchanged. D-003 at 10 mg/day, but not at 5
      mg/day, lowered (p < 0.01) plasma fibrinogen. D-003 (5 and 10 mg/day) reduced low
      density lipoprotein cholesterol (LDL-C) by 17.7% and 26.4%, respectively, and
      total cholesterol (TC) by 14.5% and 18.5%, while at 10 mg/day, but not at 5
      mg/day, it increased high-density lipoprotein cholesterol (HDL-C) by 9.6%.
      Triglycerides, however, were unchanged with D-003. No disturbances in safety
      indicators were induced with D-003. One subject (D-003 5 mg/day) discontinued the
      study and four patients (three taking D-003 and one taking placebo) reported
      adverse effects (AE) (headache in two patients taking D-003 and one patient
      taking placebo, and polyphagia in one patient taking D-003). In conclusion, D-003
      (5-10 mg/day) for 30 days inhibited platelet aggregation to AA and collagen but
      not to ADP Therefore, the antiplatelet effect was present with the longer
      treatment, even at a dose of 5 mg/day. The cholesterol-lowering effects of D-003
      were consistent with those expected for such a short treatment. In addition, D
      003 at 10 mg/day significantly lowered plasma fibrinogen. The treatment was well
      tolerated.

PMID- 15868657
TI  - Abstracts of the Nutrition Society meetings of 19-20 April 2004 and 5-8 July
      2004, United Kingdom.

PMID- 15868656
TI  - Extracellular signal-regulated kinases (ERK) 1, 2 are required for luteinizing
      hormone (LH)-induced steroidogenesis in primary Leydig cells and control
      steroidogenic acute regulatory (StAR) expression.
AB  - The luteinizing hormone (LH) plays a critical role in steroidogenesis, by
      stimulating cAMP-dependent protein kinase A (PKA) and phospholipase A2 activity,
      and by mobilizing calcium and chloride ions. In contrast, whether the ERK 1, 2
      mitogen-activated protein (MAP) kinases are involved in LH-induced
      steroidogenesis is less obvious. Here, we sought to clarify this point in rat
      primary Leydig cells, naturally bearing the LH receptor (LH-R) in male, and in
      the mouse tumoral Leydig cell line (MLTC 1). Pre-incubation of both cell types
      with the mitogen-activated protein kinase kinase (MEK) inhibitors U0126 and
      PD98059 reduced LH-induced steroidogenesis, and tonically enhanced the expression
      of the StAR protein. Furthermore, ERK1, 2 were inducibly phosphorylated following
      LH exposure of MLTC 1 cells. Altogether, our results indicate that in primary as
      well as in tumoral Leydig cells, inhibiting MEK dampened LH-induced
      steroidogenesis but enhanced basal as well as LH-induced StAR expression,
      suggesting that ERK1,2 could be involved in these responses.

PMID- 15868659
TI  - Abstracts of the 60th Annual Meeting of the Society of Biological Psychiatry. May
      19-21, 2005, Atlanta, Georgia, USA.

PMID- 15868658
TI  - Abstracts of the 45th Annual Scientific Meeting of the British Society for
      Haematology, 11-13 April 2005, Manchester, United Kingdom.

PMID- 15868660
TI  - The role of a lawyer's morals and religion when counseling clients in bioethics.

PMID- 15868661
TI  - Religious contributions to the bioethics debate: utilizing legal rights while
      avoiding scientific temptations.

PMID- 15868662
TI  - Assisted reproductive technologies and the Constitution.

PMID- 15868663
TI  - Assisted reproduction in Jewish law.

PMID- 15868664
TI  - Catholic teaching and the law concerning the new reproductive technologies.

PMID- 15868665
TI  - Protestant perspectives on the uses of the new reproductive technologies.

PMID- 15868666
TI  - The Islamic viewpoint on new assisted reproductive technologies.

PMID- 15868667
TI  - A goodness-of-fit ethic for informed consent.

PMID- 15868668
TI  - The psychology of competence and informed consent: understanding decision-making
      with regard to clinical practice.

PMID- 15868669
TI  - Protestant perspectives on informed consent (particularly in research involving
      human participants).

PMID- 15868670
TI  - Informed consent without autonomy.

PMID- 15868671
TI  - The physician's conscience, conscience clauses, and religious belief: a Catholic
      perspective.

PMID- 15868672
TI  - The physician as a conscientious objector.

PMID- 15868673
TI  - Religious teachings and reflections on advance directive--religious values and
      legal dilemmas in bioethics: an Islamic perspective.

PMID- 15868674
TI  - What is an embryo?

PMID- 15868675
TI  - What is an embryo?: a comment.

PMID- 15868676
TI  - Causative vs. beneficial complicity in the embryonic stem cell debate.

PMID- 15868677
TI  - On classifying the developing organism.

PMID- 15868678
TI  - A postmodernist take on the human embryo research debate.

PMID- 15868679
TI  - The politics of embryonic discourse.

PMID- 15868680
TI  - Developmental potential as a criterion for understanding and defining embryos.

PMID- 15868681
TI  - "What is an embryo?": a legal perspective.

PMID- 15868682
TI  - School vaccination requirements: historical, social, and legal perspectives.

PMID- 15868684
TI  - "The trouble is they're growing, the trouble is they're grown": therapeutic
      jurisprudence and adolescents' participation in mental health care decisions.

PMID- 15868685
TI  - The transinstitutionalization of the mentally ill.

PMID- 15868686
TI  - State and community collaboration: lessons from the Communities in Charge program
      and other local initiatives.

PMID- 15868687
TI  - Priority of epilepsy research in Asia.
AB  - Epilepsy is the most common serious disorder of the brain, characterized by
      recurrent unprovoked seizures. It is estimated that there are approximately 50
      million people with epilepsy worldwide, the majority of which today are living in
      the developing countries. Many countries in the Asian Oceanian regions have large
      populations and limited resources. Most such countries do have a vast health-care
      network with few centres of excellence that are comparable to the best in the
      world. The peculiar sociocultural milieu of this region provides a large
      population with epilepsy that can be used as a unique tool to conduct research
      into the basic processes, clinical aspects and psychosocial consequences of
      epilepsy. The Asian Oceanian region offers tremendous opportunities for research
      despite its limited resources. The clinicians and scientists need to be aware of
      the basic realities of the region and take full advantage of the stimulation to
      work for the benefit of humanity.

PMID- 15868688
TI  - Carotid artery stenting.

PMID- 15868689
TI  - Coronary artery stenting.

PMID- 15868690
TI  - Peripheral vessel stenting.

PMID- 15868691
TI  - Palliative medicine.

PMID- 15868692
TI  - Behavioral economics and health policy: understanding Medicaid's failure.
AB  - This Article employs a behavioral economic analysis to understand why Medicaid
      has failed to improve the health outcomes of its beneficiaries. It begins with a
      formal economic model of health care consumption and then systematically
      incorporates a survey of psychosocial variables to formulate explanations for
      persistent health disparities. This methodology suggests that consulting the
      literature in health psychology and intertemporal decision theory--empirical
      sources generally excluded from orthodox economic analysis--provides valuable
      material to explain certain findings in health econometrics. More significantly,
      the lessons from this behavioral economic approach generate useful policy
      considerations for Medicaid policymakers, who largely have neglected psychosocial
      variables in implementing a health insurance program that rests chiefly on
      orthodox economic assumptions. The Article's chief contributions include an
      expansion of the behavioral economic approach to include a host of variables in
      health psychology, a behavioral refinement of empirical health economics, a
      behavioral critique of Medicaid policy, and a menu of suggested Medicaid reforms.

PMID- 15868693
TI  - General bias and Administrative Law Judges: is there a remedy for Social Security
      disability claimants?

PMID- 15868694
TI  - [Arteriosclerosis remains the most common cause of disease and death. Prevention
      saves life and money].

PMID- 15868695
TI  - Discussion: Targeting is making trade-offs.
AB  - The previous articles presented different aspects of targeting: the implicit
      political implications, the trade-offs in giving power to different stakeholders
      to decide and to implement targeting, perceptions of frontline workers in
      implementing a program, and a technical article about selecting a scale for
      targeting, which we review in greater detail. It is well recognized that
      targeting results in a trade-off between not serving those who should be served
      and including those who should not be served. Less well recognized are the trade
      offs that are the consequences of deciding between using indicators of risk vs.
      using indicators that predict benefit.

PMID- 15868696
TI  - A cross-sectional analysis demonstrated the healthy volunteer effect in smokers.
AB  - OBJECTIVE: This cross-sectional descriptive analysis sought to determine if a
      healthy volunteer effect can be demonstrated among smokers selected to
      participate in a dietary intervention trial. STUDY DESIGN AND SETTING: Body mass
      index (BMI), body fat, physical activity, dietary intake, and plasma
      concentration of antioxidant nutrients and carotenoids were assessed cross
      sectionally, at the time of enrollment into a dietary intervention trial, among
      136 adult smokers. RESULTS: Mean BMI was below national age- and gender-specific
      averages as was prevalence of overweight and obesity. Physical activity was
      reported to average 15.4 h/wk. Compared with other sample populations of smokers,
      our smokers reported lower total fat and cholesterol intakes, higher vitamin C
      and beta-carotene intakes, and generally equal vitamin E intakes. Plasma ascorbic
      acid, alpha-tocopherol, alpha- and beta-carotene, and beta-cryptoxanthin
      concentrations were higher than those of smokers surveyed by NHANES III.
      CONCLUSION: These findings suggest that a "healthy volunteer effect" can be
      described among adult smokers. Future dietary intervention trials among smokers
      should cautiously estimate sample size because smokers electing to participate
      may report healthier dietary patterns than other smokers. Screening criteria
      regarding baseline micronutrient status of smokers should be evaluated given that
      intervention effects may be dependent on overall health status.

PMID- 15868698
TI  - Ethics for astronauts.

PMID- 15868697
TI  - Mail surveys resulted in more reports of substance use than telephone surveys.
AB  - OBJECTIVE: To determine to what extent the substance-use information obtained in
      surveys is affected by method of data collection. STUDY DESIGN AND SETTING:
      Questions on the use of alcohol and drugs were administered to samples of
      Minnesota adults assigned to one of two conditions to test the effect of mode of
      administration (mail and telephone); 816 persons completed the survey, roughly
      one half by mail and one half by telephone. RESULTS: Those interviewed by
      telephone revealed more heavy use of alcohol, but the mail sample includes
      disproportionate numbers of respondents from demographic groups that exhibit less
      use. Controlling for these differences across modes, as well as the differential
      use of listed telephone numbers and addresses, reduces the effect of mode on one
      measure of heavy alcohol use to nonsignificance but yields significant effects of
      mode on others. Specifically, those in the mail condition reported higher levels
      of illicit drug use in the last year, alcohol use in the last month, and heavy
      alcohol use in the last 2 weeks. CONCLUSIONS: The greater, and arguably more
      accurate, reporting of substance use, coupled with potential cost savings,
      suggests that researchers should consider using mail surveys for investigating
      substance use.

PMID- 15868699
TI  - Ask the ethicist: can an HIV-positive woman be forced to take medicine to protect
      her fetus?

PMID- 15868700
TI  - Dialogue: bioethics in culturally diverse societies.

PMID- 15868701
TI  - Uninsured stats continue to climb.

PMID- 15868702
TI  - Chest X-ray quiz. Pulmonary atelectasis.

PMID- 15868703
TI  - Osteoblastoma arising from the ethmoidal sinus.

PMID- 15868704
TI  - Madelung's neck: cross-sectional imaging observations.

PMID- 15868705
TI  - Using color Doppler sonography-guided reduction of intussusception to
      differentiate edematous ileocecal valve and residual intussusception.

PMID- 15868706
TI  - Successful implantation of a hepatic arterial infusion catheter through the false
      lumen in a patient with aortic dissection.

PMID- 15868707
TI  - MRI of a Morel-Lavellee lesion.

PMID- 15868708
TI  - [Electrophysiological action of carvediol on the sinus node and atrioventricular
      node cells].

PMID- 15868709
TI  - [Detection of soluble transferrin receptor-HFE complex protein in the human
      serum].

PMID- 15868710
TI  - [Dynamics of CL-P1 in ischemia/reperfusion].

PMID- 15868711
TI  - [Study on the diagnosis of prostatic cancer by detecting methylated GSTP1
      promotor region from the urinary samples].

PMID- 15868712
TI  - Lessons of the Schiavo battle.

PMID- 15868713
TI  - When does the brain go blank?

PMID- 15868714
TI  - What if it happens in your family?

PMID- 15868715
TI  - Choosing their time. The next contentious end-of-life issue: assisted suicide:
      how Oregon offers a way out.

PMID- 15868716
TI  - Secrets of the shy: why so bashful? Science finds something complex-and-cunning
      behind the curtain.

PMID- 15868717
TI  - Comparison of CFD and MRI flow and velocities in an in vitro large artery bypass
      graft model.
AB  - Bypass graft failures have been attributed to various hemodynamic factors,
      including flow stasis and low shear stress. Ideally, surgeries would minimize the
      occurrence of these detrimental flow conditions, but surgeons cannot currently
      assess this. Numerical simulation techniques have been proposed as one method for
      predicting changes in flow distributions and patterns from surgical bypass
      procedures, but comparisons against experimental results are needed to assess
      their usefulness. Previous in vitro studies compared simulated results against
      experimentally obtained measurements, but they focused on peripheral arteries,
      which have lower Reynolds numbers than those found in the larger arteries. In
      this study, we compared simulation results against measurements obtained using
      magnetic resonance imaging (MRI) techniques for a phantom model of a stenotic
      vessel with a bypass graft under conditions suitable for surgical planning
      purposes and with inlet Reynolds numbers closer to those found inthe larger
      arteries. Comparisons of flow rate and velocity profiles were performed at
      maximum and minimum flows at four locations and used simulation results that were
      temporally and spatially averaged, key postprocessing when comparing against
      phase contrast MRI measurements. The maximum error in the computed volumetric
      flow rates was 6% of the measured values, and excellent qualitative agreement was
      obtained for the through-plane velocity profiles in both magnitude and shape. The
      in-plane velocities also agreed reasonably well at most locations.

PMID- 15868718
TI  - Numerical simulation of magnetic resonance angiographies of an anatomically
      realistic stenotic carotid bifurcation.
AB  - Magnetic Resonance Angiography (MRA) has become a routine imaging modality for
      the clinical evaluation of obstructive vascular disease. However, complex
      circulatory flow patterns, which redistribute the Magnetic Resonance (MR) signal
      in a complicated way, may generate flow artifacts and impair image quality.
      Numerical simulation of MRAs is a useful tool to study the mechanisms of
      artifactual signal production. The present study proposes a new approach to
      perform such simulations, applicable to complex anatomically realistic vascular
      geometries. Both the Navier-Stokes and the Bloch equations are solved on the same
      mesh to obtain the distribution of modulus and phase of the magnetization. The
      simulated angiography is subsequently constructed by a simple geometric procedure
      mapping the physical plane into the MRA image plane. Steady bidimensional
      numerical simulations of MRAs of an anatomically realistic severely stenotic
      carotid artery bifurcation are presented, for both time-of-flight and contrast
      enhanced imaging modalities. These simulations are validated by qualitative
      comparison with flow phantom experiments performed under comparable conditions.

PMID- 15868719
TI  - Physics-driven CFD modeling of complex anatomical cardiovascular flows-a TCPC
      case study.
AB  - Recent developments in medical image acquisition combined with the latest
      advancements in numerical methods for solving the Navier-Stokes equations have
      created unprecedented opportunities for developing simple and reliable
      computational fluid dynamics (CFD) tools for meeting patient-specific surgical
      planning objectives. However, for CFD to reach its full potential and gain the
      trust and confidence of medical practitioners, physics-driven numerical modeling
      is required. This study reports on the experience gained from an ongoing
      integrated CFD modeling effort aimed at developing an advanced numerical
      simulation tool capable of accurately predicting flow characteristics in an
      anatomically correct total cavopulmonary connection (TCPC). An anatomical intra
      atrial TCPC model is reconstructed from a stack of magnetic resonance (MR) images
      acquired in vivo. An exact replica of the computational geometry was built using
      transparent rapid prototyping. Following the same approach as in earlier studies
      on idealized models, flow structures, pressure drops, and energy losses were
      assessed both numerically and experimentally, then compared. Numerical studies
      were performed with both a first-order accurate commercial software and a
      recently developed, second-order accurate, in-house flow solver. The commercial
      CFD model could, with reasonable accuracy, capture global flow quantities of
      interest such as control volume power losses and pressure drops and time-averaged
      flow patterns. However, for steady inflow conditions, both flow visualization
      experiments and particle image velocimetry (PIV) measurements revealed unsteady,
      complex, and highly 3D flow structures, which could not be captured by this
      numerical model with the available computational resources and additional
      modeling efforts that are described. Preliminary time-accurate computations with
      the in-house flow solver were shown to capture for the first time these complex
      flow features and yielded solutions in good agreement with the experimental
      observations. Flow fields obtained were similar for the studied total cardiac
      output range (1-3 1/min); however hydrodynamic power loss increased dramatically
      with increasing cardiac output, suggesting significant energy demand at exercise
      conditions. The simulation of cardiovascular flows poses a formidable challenge
      to even the most advanced CFD tools currently available. A successful prediction
      requires a two-pronged, physics-based approach, which integrates high-resolution
      CFD tools and high-resolution laboratory measurements.

PMID- 15868720
TI  - Human saphenous vein coronary artery bypass graft morphology, geometry and
      hemodynamics.
AB  - Coronary artery bypass graft (CABG) failure has been linked to graft
      hemodynamics, in particular wall shear stress. This study characterizes the
      morphology, geometry and wall shear stress patterns in human CABGs. The intimal
      thickness (IT) in 49 human saphenous vein CABGs was measured by digital light
      microscopy. The geometry of six saphenous vein CABGs was replicated by post
      mortem infusion of Batson's #17 anatomical corrosion casting compound. Graft
      hemodynamics were evaluated in two flow models, fabricated from the casts, under
      steady (Re = 110) and pulsatile flow (Re = 110, alpha = 2) conditions. Saphenous
      vein CABGs in situ for more than 2 months had, on average, the greatest IT on the
      hood and suture sites of the distal anastomosis. Floor thickening was highly
      variable and significantly less than IT at the hood, suture site and graft body.
      All casts showed an indentation along the floor and 5/6 casts displayed a sharp
      local curvature on the hood. In both flow models, a large increase in wall shear
      rate occurred on the hood, just proximal to the toe. The local geometry of the
      hood created this large spatial gradient in wall shear stress which is a likely
      factor in hood intimal hyperplasia.

PMID- 15868721
TI  - On reducing abnormal hemodynamics in the femoral end-to-side anastomosis: the
      influence of mechanical factors.
AB  - This study was concerned with investigating the influence of mechanical factors
      on the hemodynamics of the end-to-side anastomosis in an attempt to identify
      critical factors and establish if it is possible to re-engineer existing, patient
      specific, by-pass grafts with a view to increasing their patency. The study chose
      the femoral artery as the principal subject of interest. Wall shear stresses
      (WSS) and wall shear stress gradients (WSSG) were taken as the primary quantities
      of interest. Angle, graft calibre, interposition cuffs, proximal outflow and
      inlet waveform were studied. The study found that the use of cuffs and patches
      can significantly reduce abnormal WSS and WSSG by up to 70% when compared to a
      benchmark 45 degrees conventional anastomosis. The Taylor patch was found to be
      more robust in reducing peak WSS magnitudes and gradients than the Miller cuff,
      where design variables proved to be more critical. On the addition of a Taylor
      patch to a realistic end-to-side femoral anastomosis, the peak WSS and WSSG were
      found to be reduced by 27% and 57%, respectively. In conclusion, it is possible
      to use idealised models to identify critical disease influencing factors and to
      use these findings to reduce the effects of abnormal hemodynamics in realistic,
      patient-dependant models.

PMID- 15868722
TI  - Optical transillumination tomography for imaging of tissue-engineered blood
      vessels.
AB  - Recent progress in tissue engineering led to the development of completely
      biological human vessels grown from the patient's own cells. Those tissue
      engineered blood vessels (TEBV) are grown on an individual basis at high costs
      per item, and therefore require close growth monitoring and quality control. We
      designed and tested an optical transillumination tomography system using red
      laser light to image weakly scattering specimens, such as TEBV. Fixated TEBV were
      imaged and the results compared to optical coherence tomography. This preliminary
      scanner prototype had an in-plane resolution of 50 microm and allowedto see small
      inhomogeneities and defects in the samples. Tissue attenuation was found to be 70
      cm(-1). Main advantages of the transillumination tomography scanner over optical
      coherence tomography were the inexpensive instrumentation and the potential to
      rapidly acquire complete 3D sections with a CCD camera. The prototype presented
      in this study provides a basis to further improve image quality and acquisition
      speed.

PMID- 15868723
TI  - Non-uniform flow behavior in a parallel plate flow chamber : alters endothelial
      cell responses.
AB  - Arterial flow characteristics determine vessel health by modulating vascular
      endothelial cells. One system used to study these interactions is the parallel
      plate flow chamber. The present in vitro study quantified the uniformity of fluid
      flow across a parallel plate flow chamber and characterized plate-location
      dependent endothelial cell gene expression. More specifically, shear stress
      varied by as much as 11% across the chamber area, which caused non-uniform ecNOS
      (p < 0.05) and COX-2 (p < 0.05) mRNA expression across the plate area. Results
      herein suggest that chamber variations may result during construction or
      assembly, which ultimately affect flow-sensitive cell responses (including mRNA
      expression). Therefore, these limitations should be considered when reporting
      endothelial cell responses to fluid flow using parallel plate flow chambers.

PMID- 15868724
TI  - Controlling cell responses to cyclic mechanical stretching.
AB  - In most cell culture studies, cells are grown on smooth culture surfaces. Using
      microfabrication technology, we have developed microgrooved silicone surfaces to
      grow cells and subject them to repetitive mechanical stretching. When human
      patellar tendon fibroblasts were plated on these microgrooved surfaces, the cells
      had an elongated shape and underwent cyclic uniaxial stretching parallel to their
      long axes, all of which closely mimic conditions of tendon fibroblasts in vivo.
      Also, when fibroblasts were grown on microgrooves oriented at 45 and 90 degrees
      with respect to stretching direction, they did not change alignment or shape
      under cyclic mechanical stretching. Furthermore, compared to nonstretched cells,
      8% cyclic stretching of tendon fibroblasts oriented at 0 (i.e., parallel to
      stretching direction), 45, and 90 degrees was found to increase alpha-SMA protein
      expression level by 46, 31, and 14%, respectively. In addition, 8% cyclic
      stretching tendon fibroblasts for 4 and 8 h oriented parallel to stretching
      direction increased alpha-SMA protein expression level by 25 and 57%,
      respectively. Thus, the results of this study showed that alpha-SMA protein
      expression levels of tendon fibroblasts depend on cell orientation with respect
      to stretching direction and stretching duration. We suggest that microgrooved
      silicone substrates can be used to study biological responses of tendon or
      ligament fibroblasts to repetitive mechanical stretching conditions in a more
      controlled manner.

PMID- 15868725
TI  - Estimating in vitro mitochondrial oxygen consumption during muscle contraction
      and recovery: a novel approach that accounts for diffusion.
AB  - A deconvolution algorithm, based on a Bayesian statistical framework and
      smoothing spline technique, is applied to reconstructing input functions from
      noisy measurements in biological systems. Deconvolution is usually ill-posed.
      However, placing a Bayesian prior distribution on the input function can make the
      problem well-posed. Using this algorithm and a computational model of diffusional
      oxygen transport in an approximately cylindrical muscle (about 0.5-mm diameter
      and 10-mm long mouse leg muscle), the time course of muscle oxygen uptake and
      mitochondrial oxygen consumption, both during isometric twitch contractions (at
      various frequencies) and the recovery period, is estimated from polarographic
      measurements of oxygen concentration on the muscle surface. An important feature
      of our experimental protocol is the availability of data for the apparatus
      characteristics. From these time courses, the actual mitochondrial consumption
      rates during resting and exercise states can be estimated. Mitochondrial oxygen
      consumption rate increased during stimulation to a maximum steady state value
      approximately five times of the resting value of 0.63 nmol/s/g wet weight for the
      stimulation conditions studied. Diffusion slowed the kinetic responses to the
      contraction but not the steady state fluxes during the stimulation interval.

PMID- 15868726
TI  - Driving gastric electrical activity with electrical stimulation.
AB  - Gastric electrical stimulation (GES) therapy is generating a lot of interest, but
      it is still investigational. Its efficacy in driving gastric electrical activity
      and improving motility, and the ideal frequency for bringing this about are still
      controversial. In this study, a rule-based computer model of tissue electrical
      response to stimulation was developed to examine the interaction between tissue
      electrical refractoriness and the onset of tissue activation. The results were
      compared to response to GES in 8 dogs implanted with electrodes and strain gauges
      and stimulated at frequencies ranging from 3 to 30 cycles/min. Simulated
      electrical control activity at an intrinsic frequency of 5/min was entrained from
      2.0 cycles/min to 7.92 cycles/min. The regularity of the ECA elicited by
      stimulation depended on the number of pulses injected. Electrical stimulation in
      canine stomach entrained the native electrical control activity from a baseline
      average of 5.14 +/- 0.32 cycles/min up to 9.2 cycles/min. Contractile response to
      stimulation at 20-30 cycles/min were significantly higher (p < 0.05). Computer
      simulation of GES may be a useful tool to complement and reduce some of the costs
      associated with empirical studies of gastric electrical stimulation in
      establishing its possible use in treating drug refractory gastroparesis.

PMID- 15868727
TI  - Asymmetric and axisymmetric constant curvature liquid-gas interfaces in pulmonary
      airways.
AB  - Airway closure and gas trapping can occur during lung deflation and inflation
      when fluid menisci form across the lumina of respiratory passageways. Previous
      analyses of the behavior of liquid in airways have assumed that the airway is
      completely wetted or that the contact angle of the liquid-gas interface with the
      airway wall is 0 degrees, and thus that the airway fluid forms an axisymmetric
      surface. However, some investigators have suggested that liquid in the airways is
      discontinuous and that contact angles can be as high as 67 degrees. In this study
      we consider the characteristics of constant curvature surfaces that could form a
      stable liquid-gas interface in a cylindrical airway. Our analysis suggests that,
      for small liquid volumes, asymmetric droplets are more likely to form than
      axisymmetric toroids. In addition, if the fluid contact angle is greater than 13
      degrees, asymmetric droplets can sustain larger liquid volumes than axisymmetric
      toroids before collapsing to form menisci. These results suggest that (1) fluid
      formations other than axisymmetric toroids could occur in the airways; and (2)
      the analysis of the behavior of fluids and the development of liquid menisci
      within the lungs should include the potential role of asymmetric droplets.

PMID- 15868728
TI  - Substrate curvature influences the direction of nerve outgrowth.
AB  - Nerve outgrowth in the developing nervous system utilizes a variety of attractive
      and repulsive molecules found in the extracellular environment. In addition,
      physical cues may play an important regulatory role in determining directional
      outgrowth of nervous tissue. Here, by culturing nerve cells on filamentous
      surfaces and measuring directional growth, we tested the hypothesis that
      substrate curvature is sufficient to influence the directional outgrowth of nerve
      cells. We found that the mean direction of neurite outgrowth aligned with the
      direction of minimum principle curvature, and the spatial variance in outgrowth
      direction was directly related to the maximum principle curvature. As substrate
      size approached the size of an axon, adherent neurons extended processes that
      followed the direction of the long axis of the substrate similar to what occurs
      during development along pioneering axons and radial glial fibers. A simple
      Boltzmann model describing the interplay between adhesion and bending stiffness
      of the nerve process was found to be in close agreement with the data suggesting
      that cell stiffness and substrate curvature can act together in a manner that is
      sufficient to direct nerve outgrowth in the absence of contrasting molecular
      cues. The study highlights the potential importance of cellular level geometry as
      a fidelity-enhancing cue in the developing and regenerating nervous system.

PMID- 15868729
TI  - Evaluation of three growth factors for TMJ disc tissue engineering.
AB  - Arguably one of the most complex joints in the body, the temporomandibular joint
      (TMJ) presents one of the most difficult problems in modem medicine. Tissue
      engineering, for the TMJ disc in particular, has been proposed as a potential
      breakthrough treatment strategy for TMJ disorders. Central to tissue engineering
      is understanding growth factor effects on TMJ disc cells, and to the best of our
      knowledge, this is the first 3D growth factor study for these cells. The purpose
      was to examine the effects of high and low concentrations of basic fibroblast
      growth factor (bFGF), insulin-like growth factor-I (IGF), and transforming growth
      factor-beta1 (TGF-beta) on porcine TMJ disc cells. Cells were seeded onto non
      woven PGA scaffolds (95% porosity) in spinner flasks, then cultured with a growth
      factor for 6 weeks. Constructs were analyzed for mechanical and structural
      integrity, cell number, and matrix biosynthesis. All growth factors improved
      mechanical and structural integrity compared to the control. IGF and TGF-beta
      were most effective at promoting collagen synthesis, although there were no
      significant differences in glycosaminoglycan synthesis or cell number between any
      groups. After considering the economic advantage of IGF over TGF-beta, the
      conclusion of this study is to use IGF in future TMJ disc tissue engineering
      experiments.

PMID- 15868730
TI  - Human lumbar spine creep during cyclic and static flexion: creep rate,
      biomechanics, and facet joint capsule strain.
AB  - There is a high incidence of low back pain (LBP) associated with occupations
      requiring sustained and/or repetitive lumbar flexion (SLF and RLF, respectively),
      which cause creep of the viscoelastic tissues. The purpose of this study was to
      determine the effect of creep on lumbar biomechanics and facet joint capsule
      (FJC) strain. Specimens were flexed for 10 cycles, to a maximum 10 Nm moment at
      L5-S1, before, immediately after, and 20 min after a 20-min sustained flexion at
      the same moment magnitude. The creep rates of SLF and RLF were also measured
      during each phase and compared to the creep rate predicted by the moment
      relaxation rate function of the lumbar spine. Both SLF and RLF resulted in
      significantly increased intervertebral motion, as well as significantly increased
      FJC strains at the L3-4 to L5-S1 joint levels. These parameters remained
      increased after the 20-min recovery. Creep during SLF occurred significantly
      faster than creep during RLF. The moment relaxation rate function was able to
      accurately predict the creep rate of the lumbar spine at the single moment
      tested. The data suggest that SLF and RLF result in immediate and residual laxity
      of the joint and stretch of the FJC, which could increase the potential for LBP.

PMID- 15868731
TI  - Derivation of centers and axes of rotation for wrist and fingers in a hand
      kinematic model: methods and reliability results.
AB  - In the field of 3D reconstruction of human motion from video, model-based
      techniques have been proposed to increase the estimation accuracy and the degree
      of automation. The feasibility of this approach is strictly connected with the
      adopted biomechanical model. Particularly, the representation of the kinematic
      chain and the assessment of the corresponding parameters play a relevant role for
      the success of the motion assessment. In this paper, the focus is on the
      determination of the kinematic parameters of a general hand skeleton model using
      surface measurements. A novel method that integrates nonrigid sphere fitting and
      evolutionary optimization is proposed to estimate the centers and the functional
      axes of rotation of the skeletal joints. The reliability of the technique is
      tested using real movement data and simulated motions with known ground truth 3D
      measurement noise and different ranges of motion (RoM). With respect to standard
      nonrigid sphere fitting techniques, the proposed method performs 10-50% better in
      the best condition (very low noise and wide RoM) and over 100% better with
      physiological artifacts and RoM. Repeatability in the range of a couple of
      millimeters, on the localization of the centers of rotation, and in the range of
      one degree, on the axis directions is obtained from real data experiments.

PMID- 15868732
TI  - Faith in our future?

PMID- 15868733
TI  - Healthy? Think again.

PMID- 15868734
TI  - Rethinking abnormal behavior.

PMID- 15868735
TI  - Granulysin induces cell death with nuclear accumulation.
AB  - Exogenously added granulysin was reported to kill mammalian target cells. The
      sites of actions and molecular mechanisms of granulysin in target cell killing,
      however, are presently unclear. We here examine the effects of granulysin with
      the target HeLa cells transiently expressed with GFP-fused 9 kDa granulysin.
      Endogenously expressed GFP-fused granulysin was preferentially localized in the
      nucleus and induced apoptotic cell death accompanying with phosphatidylserine
      translocation and nuclear condensation in a caspase-independent manner. These
      results suggest that granulysin enters the nucleus of target cells and induces
      apoptosis.

PMID- 15868736
TI  - Effect of various grit burs on marginal integrity of resin composite
      restorations.
AB  - The purpose of this study was to evaluate the generation of enamel cracks and
      gaps at the cavosurface margin of resin composite restorations using various
      burs. Saucer-shaped cavities with a bevel were prepared on mid-coronal buccal or
      lingual surfaces of extracted human molars using a regular-grit round diamond
      bur, a fine-grit diamond bur, a superfine-grit diamond bur or a six-bladed
      tungsten carbide bur with an air turbine handpiece. The enamel margin of the
      cavity in each group was observed by a light microscope. Cavities were restored
      with a self-etching adhesive and a light-cured composite resin. After
      thermocycling, enamel cracks and gaps at the cavosurface margins were observed
      and scored. Specimens were sectioned longitudinally in two halves, and the resin
      cavity interface was observed by means of a light microscope. In cavity
      preparation, the regular-grid diamond bur and the tungsten carbide bur caused
      more cracks in the marginal enamel than other groups. From the surface and
      sectioned surface observation of restored teeth, the superfine-grit diamond bur
      generated fewer cracks and gaps than the other burs.

PMID- 15868737
TI  - Coverage by Japanese newspapers of oral health messages on the prevention of
      dental caries.
AB  - The purpose of this study was to estimate the coverage and quality of information
      on dental caries prevention in Japanese newspapers. Newspaper articles were
      searched using database during 10 years from 1993 to 2002. From five major
      newspapers, 440 articles concerning dental caries prevention were selected and
      used for analysis. The number of caries prevention articles was related to
      National Oral Health Week, which was held in June of each year, and the
      introduction of new policy or government statements on oral health issues. Major
      sources of articles came from manufacturing companies (29.3%), staff of
      universities (27.7%), and other dental specialists (20.2%). Caries prevention
      articles appeared frequently in the health columns (35.7%) followed by news
      articles (20.0%) and business columns (17.7%). Dietary control (47.5%) was the
      most frequently described preventive method. Plaque control was referred to in
      40.9% of articles, and information about improvement of host factors was provided
      in 40.0%. Among them, fluoride information was included in 30.0%. Clearly wrong
      information against evidence based were found in 24 articles. It is important
      that newspapers provide accurate information with a supportive evidence base.
      Dental professionals in Japan should be aware of the importance of media advocacy
      in order to provide appropriate oral health information to the public.

PMID- 15868738
TI  - Correlation of in vivo bone formation capability and in vitro differentiation of
      human bone marrow stromal cells.
AB  - Although human bone marrow stromal cells (MSCs) have been used for clinical bone
      reconstruction, how the physiological status of patients and culture conditions
      of MSCs affect the result of bone reconstruction must be clarified to use MSCs in
      a clinical stage. If in vitro parameters of the status of MSCs may be correlate
      with in vivo bone formation capability, the better cells for clinical bone
      reconstruction can be defined by the parameters. In order to explore the
      parameters and define the optimum cells for clinical use, the proliferation and
      differentiation capabilities in vitro and the in vivo bone formation capability
      of MSCs were analyzed. An age-related proliferation capability was found. The in
      vitro alkaline phosphatase activity of bone formation finding groups was higher
      than that of the no bone formation group. This may be provide a parameter to
      obtain the optimum cells for clinical use to benefit improving the cure
      efficiency. In this study, it is preferable that MSCs of passage 1 have stronger
      osteogenic potential than those of passage 2 and 3 in vitro, and might be
      suitable for clinical application to bone tissue engineering.

PMID- 15868739
TI  - Masticatory function after unilateral distal extension removable partial denture
      treatment: intra-individual comparison with opposite dentulous side.
AB  - Due to large individual differences of masticatory function, an inter-individual
      comparison between denture patients and complete dentate people would be
      insufficient. This cross-sectional study aimed to evaluate patients' masticatory
      performance (determined by Mixing Ability Index, MAI) and bite force (determined
      by maximum bite force, MBF) after removable partial denture (RPD) treatment by
      comparing those of the RPD replaced side with those of their own opposite
      dentulous side, and to evaluate influence of bite force on masticatory
      performance in different dentitions. Subjects included patients with unilateral
      distal extension RPDs (n=28). Apart from the RPD replaced area on one-side, all
      subjects had intact dentitions. Both masticatory parameters were evaluated
      separately on each chewing side. MAls and MBFs obtained from the RPD replaced
      side (0.65 +/- 0.50 and 220 +/- 155 N, mean +/- SD) were significantly lower than
      those from the dentulous side (1.06 +/- 0.64 and 450 +/- 268 N; Wilcoxon signed
      ranks, P < 0.001). MBF significantly influenced MAI in both RPD replaced
      (Univariate linear regression; R2 = 0.17, P < -0.001) and dentulous sides (R2 =
      0.51, P < 0.001). After RPD treatment, masticatory performance and bite force of
      RPD replaced side were lower than those of their own dentulous side. The
      influence of the bite force on masticatory performance in RPD replaced side was
      less significant than that in the dentulous side.

PMID- 15868740
TI  - Reverse 'see-saw' relationship between Graves' disease and myasthenia gravis;
      clinical and immunological studies.
AB  - Although the association of two distinct autoimmune diseases, Graves' disease
      (GD) and myasthenia gravis (MG), is rare, the relationships of clinical and
      immunological activities between the two diseases remain unknown. In the present
      study, we investigated whether there exist any relationships between clinical and
      immunological activities of GD and MG as well as any common characteristics of
      their HLA antigens in five patients with concomitant association with GD and MG.
      The present study clearly showed positive relationships between the clinical
      activities of GD and MG in all five cases. Except for two cases, one with
      undetectable acetylcholine receptor antibody and another with few sample number,
      there were positive relationships between two circulating auto-antibodies against
      TSH receptor and acetylcholine receptor as well as their immunological and
      clinical activities in the remaining three cases. Furthermore, the present
      serological HLA typing study revealed that all five cases had common HLA-DQ3.
      Therefore, our study clearly demonstrates a reverse 'see-saw' relationship
      between GD and MG based on their clinical and immunological features, and
      suggests that HLA-DQ3 may play a potential pathogenic role in the concomitant
      development of the two diseases.

PMID- 15868741
TI  - Beta-tricalcium phosphate (beta-TCP) graft combined with bone marrow stromal
      cells (MSCs) for posterolateral spine fusion.
AB  - Macaque lumber posterolateral spine fusion (PLF) was performed by using beta-TCP
      graft combined with bone marrow derived stromal cells (MSCs), to evaluate whether
      a beta-TCP/MSCs hybrid can be used for PLF instead of autogenous bone graft. Nine
      crab-eating macaque underwent bilateral PLF at L4-L5. The implants were divided
      into three groups: 1) beta-TCP/MSCs hybrid, 2) autogenous bone, and 3) beta-TCP.
      Six monkeys were sacrified at 12 weeks and three monkeys were sacrificed at 24
      weeks after implantation. Manual palpation, radiography, micro computed
      tomography, peripheral quantitative computed tomography (pQCT), and histology
      were used to assess bone formation. Manual palpation and X-ray showed that 83.3%
      of hybrid groups and 66.7% of autogenous groups achieved solid spine fusion,
      whereas none of other groups fused. Histological analysis showed that all of the
      hybrid groups achieved massive bone formation. Bone mineral density (BMD)
      evaluated with pQCT in the hybrid groups increased by additional new bone. Beta
      TCP/MSCs hybrid can be used for PLF instead of autogenous bone graft. Thus it can
      be hypothesized that the monkey PLF can simulate human PLF.

PMID- 15868742
TI  - Occlusal forces promote periodontal healing of transplanted teeth with enhanced
      nitric oxide synthesis.
AB  - It has been reported that occlusal forces promote periodontal healing of
      transplanted teeth and prevent dentoalveolar ankylosis, although its mechanism is
      still unclear. Nitric oxide (NO) produced by NO synthase (NOS) is considered to
      be an important factor which is involved in wound healing, and it increases with
      mechanical stimuli. The objective of this study was to examine the relationship
      among occlusal stimuli, inducible NOS (iNOS) and PDL healing of transplanted
      teeth. Five-week-old Sprague-Dawley male rats were used for this study. The right
      maxillary first molars of rats were replanted and animals were divided into
      occluded and non-occluded groups. Histologic observations were carried out after
      one and two weeks. After two weeks, the non-occluded group had clearly detectable
      ankylosis and obvious PDL stricture. On the other hand, the occluded group showed
      an enlarged and thickened PDL without ankylosis. The number of iNOS positive
      cells in the occluded group, samples significantly increased in comparison to
      that of the non-occluded group. These results suggest that occlusal stimuli
      enhanced the production of NO in the PDL healing process of transplanted teeth
      and a favorable result could be obtained.

PMID- 15868743
TI  - An evaluation of self-reported oral health and health-related quality of life.
AB  - The purpose of this study was to investigate the general and oral health status
      of patients at a dental hospital in Tokyo and examine the correlations between
      general health and oral health items. One hundred and seventy-four (174) new
      patients at the Dental Hospital of Tokyo Medical and Dental University
      participated in this study. The Visual Analog Scale (VAS) was employed to
      investigate dental demands and symptoms, as well as satisfaction with oral and
      general health conditions, while SF-36 served an indicator for health-related
      quality of life (HRQOL). The results were statistically analyzed at a
      significance level of p = 0.05. The results of VAS were further examined using
      factor analysis. Several VAS items showed significant correlations with SF-36
      subscales (p<0.05). The factor analysis of VAS items suggested a structure
      involving three factors: self-cognition of oral status, related function and
      pain, and dental fear and discomfort. The dental fear and discomfort factor
      showed no significant correlations with SF-36 subscales (p>0.05). Emotional
      elements and esthetic demands on dental status, as well as physical symptoms,
      influence HRQOL. Dental discomfort proved to be independent of general health
      status and was considered a dental-specific item that needs to be measured
      separately from general health status.

PMID- 15868744
TI  - Relationship between oral sensory thresholds and depressive moods.
AB  - AIMS: The aims were to compare the sensory thresholds on the tip of the tongue
      with on the dorsum of the hand, and to investigate the relationship between the
      sensory threshold and depressive mood with volunteers whose psychological
      conditions were normal. METHODS: Fifty-five subjects (28 women, 27 men) took
      psychiatric structured diagnostic interview and Self-rating Depression Scale
      (SDS). In the next step, the quantitative sensory tests (light touch sensation
      and thermal sensory test) were carried out on the tongue and the hand. Then we
      investigated the relationship between depressive moods and sensory thresholds on
      the tongue and the hand using logistic regression model. RESULT: The sensory
      thresholds on the tip of the tongues were significantly different from those on
      the dorsum of the hands. Only on tongue tip, increment of SDS had relation to the
      thresholds of innoxious thermal stimulation (OR=0.152, 95% CI. 0.049-0.478) and
      noxious heat stimulation (OR=0.352, 95% CI. 0.169-0.734). CONCLUSION: This
      finding might support for the idea that depressive mood had closer association
      with the tongue of the orofacial areas than the dorsum of the hand.

PMID- 15868745
TI  - Current practices and problems in the reuse of single-use devices in Japan.
AB  - Along with the popularization of endoscopic surgeries, the reuse of disposable
      single-use devices (SUDs), which may cause various risks, has become a
      considerable issue globally. We conducted the survey by questionnaires for the
      operating room (OR) head nurses to obtain hospital-based answer. First survey was
      done for three months in 2000 by sending the questionnaires to 2,224 hospitals.
      The second survey was done in 2003. In addition, for trocars and endoscopic
      clips, we carried out laboratory functional tests for the reuse of these
      reprocessed devices. As a total, 94.4% of hospitals reused SUDs routinely. The
      second survey showed significant decrease in the frequency of reuse to 86.2% as a
      whole. In the sample study, gross inspection showed the existence of
      contamination with debris. In-vitro sample study on in-hospital reprocessed
      instruments also demonstrated damaged endoscopic clips with impaired holding
      power. This study has demonstrated a still high frequency of reuse of SUDs in
      endoscopic surgeries in Japan. Although financial background may be the main
      reason, what is necessary to promote the single use of SUDs are multidisciplinary
      and composite approaches including an effort to lower the product price in
      parallel with the establishment of regulation and education programs.

PMID- 15868746
TI  - Subcutaneous injections of a TNF-alpha antagonistic peptide inhibit both
      inflammation and bone resorption in collagen-induced murine arthritis.
AB  - The cyclic peptide WP9QY (YCWSQYLCY), which was designed to mimic the most
      critical tumor necrosis factor (TNF) alpha recognition loop on type1 TNF
      receptor, antagonizes the effects of TNFalpha. In this study, we investigated the
      effects of WP9QY peptide on collagen-induced arthritis (CIA) mice to evaluate its
      effects on inflammatory bone destruction. DBA/1J mice were injected intradermally
      at the base of the tail with bovine type II collagen, emulsified in complete
      Freund's adjuvant on day 0 and 21. The three sets of WP9QY peptide injections (24
      mg/kg x 8 times per day) were performed before the onset of paw swelling. Mice
      were sacrificed at day 38 and thereafter, the arthritis scores as well as
      radiographical and histological outcomes were assessed. WP9QY peptide inhibited
      CIA-induced increase in the arthritis score. Furthermore, histomorphometric
      analysis of the tibial epiphysis region revealed that WP9QY peptide inhibited the
      increase of synovial pannus infiltration and the decrease of bone volume, which
      were induced by the CIA. The WP9QY treatment prevented the inflammation as well
      as bone destruction of the joints in the CIA mice, suggesting that the
      administration of WP9QY peptide might be useful for developing a drug to prevent
      inflammatory bone destruction.

PMID- 15868748
TI  - Drug interaction screens are pharmacists' responsibility.

PMID- 15868747
TI  - Systems-based approach to risk management.

PMID- 15868749
TI  - International Journal of Pharmacy Practice: another avenue for publication.

PMID- 15868750
TI  - Approaches and attitudes: assessing the mindset of pharmacy.

PMID- 15868751
TI  - More research needed to better understand what contributes to job satisfaction.

PMID- 15868752
TI  - Attitudes vary, but students united by common bond.

PMID- 15868753
TI  - Measuring adherence in community pharmacies: opportunities and challenges.

PMID- 15868754
TI  - Patient self-management program for diabetes: first-year clinical, humanistic,
      and economic outcomes.
AB  - OBJECTIVE: To assess the outcomes for the first year following the initiation of
      a multisite community pharmacy care services (PCS) program for patients with
      diabetes. DESIGN: Quasi-experimental, pre-post cohort study. SETTING: 80
      community pharmacy providers with diabetes certificate program training who were
      reimbursed for PCS by employers in Greensboro, N.C., Wilson, N.C., Dublin, Ga.,
      Manitowoc County, Wis., and Columbus, Ohio. PATIENTS: 256 patients with diabetes
      covered by self-insured employers' health plans. INTERVENTIONS: Community
      pharmacist patient care services using scheduled consultations, clinical goal
      setting, monitoring, and collaborative drug therapy management with physicians
      and referrals to diabetes educators. MAIN OUTCOME MEASURES: Changes in
      glycosylated hemoglobin (AIC), low-density lipoprotein cholesterol (LDL-C), blood
      pressure, influenza vaccinations, foot examinations, eye examinations, patient
      goals for nutrition, exercise, and weight, patient satisfaction, and changes
      medical and medication utilization and costs. RESULTS: Over the initial year of
      the program, participants' mean A1C decreased from 7.9% at initial visit to 7.1%,
      mean LDL-C decreased from 113.4 mg/dL to 104.5 mg/dL, and mean systolic blood
      pressured decreased from 136.2 mm Hg to 131.4 mm Hg. During this time, influenza
      vaccination rate increased from 52% to 77%, the eye examination rate increased
      from 46% to 82%, and the foot examination rate increased from 38% to 80%. Patient
      satisfaction with overall diabetes care improved from 57% of responses in the
      highest range at baseline to 87% at this level after 6 months, and 95.7% of
      patients reported being very satisfied or satisfied with the diabetes care
      provided by their pharmacists. Total mean health care costs per patient were $918
      lower than projections for the initial year of enrollment. CONCLUSION: Patients
      who participated in the program had significant improvement in clinical
      indicators of diabetes management, higher rates of self-management goal setting
      and achievement, and increased satisfaction with diabetes care, and employers
      experienced a decline in mean projected total direct medical costs.

PMID- 15868755
TI  - Impact of community pharmacy automation on workflow, workload, and patient
      interaction.
AB  - OBJECTIVE: To compare workload productivity, workflow efficiency, and pharmacist
      patient interaction in automated and nonautomated community pharmacies. DESIGN:
      Observational study. SETTING: Four community pharmacy sites within a regional
      pharmacy chain. STUDY PARTICIPANTS: 173 patients and 11 pharmacists.
      INTERVENTIONS: Patient surveys, pharmacist surveys, and direct observation. MAIN
      OUTCOME MEASURES: Patient satisfaction, frequency of pharmacist-patient
      interactions, and prescription dispensing productivity and efficiency. RESULTS:
      Results from the three nonautomated pharmacies were averaged and compared with
      results from the automated pharmacy. Patient satisfaction was generally favorable
      for both automated and nonautomated pharmacies, but scores for the automated site
      were significantly better on items measuring one domain, technical competence of
      pharmacy staff. No association was found between patient counseling and
      prescription workload in automated or nonautomated sites. Personnel at the
      automated site made significantly more offers to counsel patients, but the number
      of patients who received counseling did not differ significantly. Automation was
      associated with a higher number of prescriptions dispensed per full-time
      equivalent pharmacist and fewer technical dispensing tasks performed by
      pharmacists. CONCLUSION: Patient satisfaction was not related to the presence of
      an automated dispensing system. Automation was associated with higher
      prescription productivity, but actual counseling rates were no different from
      those observed in nonautomated pharmacies. The likelihood that a patient would
      receive counseling was not related to staffing levels, automation, or workload.
      Whether counseling occurred appeared to depend on factors other than automation.

PMID- 15868756
TI  - Assessment of workflow redesign in community pharmacy.
AB  - OBJECTIVE: To assess the effect that workflow enhancements have on dispensing
      responsibilities and pharmacist-patient interaction in the community pharmacy
      setting. DESIGN: Pre-post comparison. Pre-assessment data were obtained from a
      multisite observational study. SETTING: Pharmacy within a regional pharmacy
      chain. STUDY PARTICIPANTS: 3 pharmacists and 110 patients. INTERVENTION: The
      pharmacy was physically remodeled to enable workflow changes, including defining
      dispensing responsibilities with an emphasis on patient counseling, providing an
      additional 6 feet of counter space, upgrading technology, installing a third
      computer, implementing tools to augment the filling process, and requesting that
      cashiers rephrase the offer to counsel to encourage patient acceptance. Patients
      and pharmacists were surveyed about the experiences and beliefs, and pharmacy
      activities were observed directly. MAIN OUTCOME MEASURES: Patient counseling and
      prescription dispensing. activities. RESULTS: The number of pharmacists who
      perceived that they had adequate time to counsel patients increased as a result
      of the intervention (0 of 3 responding pharmacists before the intervention,
      compared with 2 of 2 afterward). Patient satisfaction scores both before and
      after the intervention were predominantly favorable and did not differ
      significantly. The most relevant change in dispensing activities was pharmacist
      involvement with data entry into the computer, which decreased from 61% to 10%.
      Oral counseling offers to patients increased significantly, from 5% to 85%, but
      counseling rates remained low throughout the study and were not measurably
      affected by workload. CONCLUSION: Workflow redesign has positively affected the
      dispensing activities at the study site. Technicians took more responsibility for
      dispensing tasks. Given the drastic increase in counseling offers but lack of
      effect on counseling rates, patient behavior and expectations with regard to
      counseling likely need to change to further improve dynamics in the community
      pharmacy.

PMID- 15868757
TI  - Concordance among three self-reported measures of medication adherence and
      pharmacy refill records.
AB  - OBJECTIVE: To evaluate the level of agreement among three previously validated
      self-reported medication adherence measures and pharmacy refill records (RRs).
      DESIGN: Cross-sectional study. SETTING: Five primary care physician office sites
      in rural northeast Georgia. PARTICIPANTS: 139 adult patients with one or more of
      these chronic diseases: hypertension, diabetes mellitus, hypercholesterolemia,
      hypothyroidism, or a condition requiring hormone replacement therapy.
      INTERVENTIONS: Study participants completed the Brief Medication Questionnaire
      (BMQ), the Medication Adherence Survey (MAS), and the Medical Outcomes Study
      (MOS) instruments; pharmacy RRs for the medication or medications being used to
      treat the target disease were obtained from pharmacies used by the study
      participants. MAIN OUTCOME MEASURES: Adherence to medication therapy for target
      disease. RESULTS: Participants were nearly all white (98.6%), consistent with the
      Appalachian area in which the study was conducted, and mostly women (71.9%).
      While 91.4% of study participants reported taking their study medication most or
      all of the time, RRs showed mean adherence rates of 82.6%, 82.1%, 79.1%, 74.6%,
      and 69.8% for diabetes mellitus, hypertension, hypothyroidism,
      hypercholesterolemia, and hormone replacement therapy, respectively. Moderate
      correlations of .234, .261, and .213 were found between RRs and the MAS, MOS, and
      BMQ belief screen, respectively. Spearman correlations ranged from .091 between
      RRs and the BMQ regimen subscale to .313 between MOS and MAS. Pearson chi-square
      tests showed that only the BMQ belief subscale was significant in this study.
      CONCLUSION: Because of the weak to moderate concordance found among validated
      measures of adherence, the selection of a useful adherence measure in pharmacy
      practice is difficult. These findings underscore the difficulty in both assessing
      patients' medication-taking behavior and assessing and comparing the results of
      adherence research. The development of valid and reliable measures for easily
      assessing medication adherence behavior in community pharmacies is needed.

PMID- 15868758
TI  - Drug therapy concerns questionnaire: initial development and refinement.
AB  - OBJECTIVE: To develop a scale, designed for self-administration, to assess
      patient perceptions of drug therapy problems (DTPs). DESIGN: Cross-sectional
      survey. SETTING: California Central Valley. PARTICIPANTS: 200 community-dwelling
      adults taking at least one prescription medication. MAIN OUTCOME MEASURE: 78
      items assessing patient perceptions of DTPs. INTERVENTIONS: Self-administered
      questionnaire completed by study participants. RESULTS: Based on a Medication
      Evaluation and Response Model proposed in this article, items were developed to
      assess patient perceptions about potential or actual DTPs. Scales for five of the
      seven problem domains specified a priori were reliable based on participant
      responses: Perceived Efficacy, Overmedication Concerns, Adverse Drug Reaction
      Concerns, Adherence Issues, and Knowledge. Barriers and Intrusiveness were
      eliminated from, the questionnaire because of weak factor loadings. After making
      changes in domain assignment and eliminating redundant and weak items, five items
      remained in each of the five reliable scales, with Cronbach's alpha values
      ranging from 0.76 to 0.82. Each of the five scales was significantly associated
      with patient satisfaction with their medications. Individuals who reported fewer
      DTPs expressed greater overall satisfaction with their medications. In a forward
      stepwise regression analysis, four of the five scales exhibited independent
      associations with medication satisfaction, explaining 58.0% of the total variance
      in satisfaction [F(4,178) = 61.48, P < .0001]. Only the Knowledge scale failed to
      exhibit an independent association with satisfaction. CONCLUSION: The findings
      from this initial stage of scale development are encouraging. The association
      between the scales and medication satisfaction suggests that the scales may be
      useful in learning more about those factors that influence how patients evaluate
      their medications.

PMID- 15868759
TI  - Evaluation of pharmacist-managed nonprescription drug benefit for Canadian
      military personnel.
AB  - OBJECTIVES: To determine whether (1) desirable health outcomes (e.g., symptom
      resolution) would be achieved with a new national drug-management program
      implemented by the Canadian Forces (CF); (2) CF members would be satisfied with
      the services offered by the civilian pharmacists; and (3) cost implications of
      the new program would be favorable. DESIGN: Open, nonrandomized, longitudinal
      program evaluation and cost analysis study. SETTING: Canada. PARTICIPANTS: 583 CF
      members who did not have access to a military pharmacy in selected geographic
      areas of Canada and 65 community pharmacy providers. INTERVENTION: A new drug
      management program, which allowed members to obtain nonprescription medications
      from civilian pharmacies without first obtaining a prescription from a physician
      at no additional cost, was evaluated in a pilot study. MAIN OUTCOME MEASURES: A
      cost-analysis model conducted from the CF Health Services and Department of
      National Defense perspectives and telephone survey assessing health outcomes and
      members' satisfaction with the program. RESULTS: Based on 563 transactions that
      occurred during the pilot study period, 96% of the CF members reported being very
      to somewhat satisfied with the service received under the new drug-management
      program, and a majority stated that desirable health outcomes were achieved. The
      one area of concern cited about the new program was the low percentage of members
      who recalled being instructed by civilian pharmacists to see a physician if their
      symptoms did not abate. The cost analysis showed the new program was more
      economical than previous physician-based system. CONCLUSION: The provision of
      nonprescription medications by civilian pharmacists to members who had no access
      to a base pharmacy was both cost-efficient and associated with a high level of
      satisfaction. Future evaluations should include prospective monitoring of drug
      use patterns as well as assessments of the quality of care.

PMID- 15868760
TI  - Community pharmacists' awareness of and involvement with medications intended for
      use in primary and secondary schools.
AB  - OBJECTIVE: To observe the degree to which community pharmacists are aware of and
      involved in issues related to the use of medications in primary and secondary
      schools and to identify the interventions they use to deal with these issues.
      DESIGN: Cross-sectional survey. SETTING: Illinois. PARTICIPANTS: 569 licensed
      pharmacists with community pharmacy experience. INTERVENTIONS: A survey
      comprising questions about the experiences, attitudes, and behaviors of community
      pharmacists with regard to medication use in schools was mailed in June 2003.
      MAIN OUTCOME MEASURES: Descriptive and bivariate statistical analysis of survey
      items. RESULTS: Almost all respondents reported that they had dispensed
      medications for use in school; two thirds thought that taking medications at
      school creates the potential for special problems (e.g., missed dose, social
      stigma). Of nine interventions that could help minimize these problems, the
      respondents used a mean of 3.34 interventions. Providing additional labeled
      containers for use at school was the most common intervention reported.
      Respondents who thought that medication use in schools caused special problems
      provided significantly more interventions than those that did not share this
      concern. CONCLUSION: Pharmacists are aware of and involved in the issues and
      potential problems created by medication use in schools. While they make use of
      interventions that are available to all community pharmacists, they could do more
      to help resolve issues. Additional effort to raise pharmacist awareness about
      medication use in schools is warranted.

PMID- 15868761
TI  - New drugs of 2004.
AB  - OBJECTIVES: To provide information regarding the most important properties of the
      new therapeutic agents marketed in 2004. DATA SOURCES: Product labeling
      supplemented selectively with published studies and drug information reference
      sources. STUDY SELECTION: By the author. DATA EXTRACTION: By the author. DATA
      SYNTHESIS: The 22 new therapeutic agents marketed in the United States during
      2004 are reviewed in this article. Indications and information on dosage and
      administration for these agents are reviewed, as are the most important
      pharmacokinetic properties, adverse events, drug interactions, and other
      precautions. Practical considerations for the use of the new agents are also
      discussed. When possible, the properties of the new drugs are compared with those
      of older drugs marketed for the same indications. CONCLUSION: A number of the new
      therapeutic agents marketed in 2004 have important advantages over older
      medications. An understanding of the properties of these agents is important for
      the pharmacist to effectively counsel patients about their use and to serve as a
      valuable source of information for other health professionals regarding these
      drugs.

PMID- 15868762
TI  - Carl Thomas Durham (1892-1974): pharmacy's representative.

PMID- 15868763
TI  - Not too early to prepare for upcoming influenza season.

PMID- 15868764
TI  - New drugs: palifermin, eszopiclone, and darifenacin hydrobromide.

PMID- 15868765
TI  - OTC product: metamucil plus calcium for regularity and calcium supplementation.

PMID- 15868766
TI  - Managing cardiovascular risk in minority patients.
AB  - In the United States, large and growing minority populations, including African
      Americans, Hispanic Americans and South Asians, are highly susceptible to the
      development of cardiovascular disease. Compared with Americans of other
      ancestries, these populations exhibit a higher prevalence of a number of risk
      factors, such as dyslipidemia, hypertension, obesity and diabetes mellitus. The
      clustering of risk factors in these groups is also greater than in white
      populations. Despite the considerable burden imposed by cardiovascular disease,
      African Americans, Hispanic Americans and South Asians remain inadequately
      targeted for risk-reduction strategies, including screening and treatment for
      dyslipidemia. In addition, these groups have traditionally been underrepresented
      in trials of lipid-modifying therapy. Large, ongoing epidemiologic and clinical
      trials will add to our knowledge of cardiovascular risk in these minority
      populations and contribute to recommendations to improve risk management.

PMID- 15868767
TI  - Workplace discrimination: experiences of practicing physicians.
AB  - BACKGROUND: In response to a growing concern regarding physician discrimination
      in the workplace, this study was developed to: (1) describe the types of
      discrimination that exist for the practicing physician and (2) determine which
      groups of physicians are more likely to experience the various forms of
      discrimination. METHODS: Surveys were mailed to 1930 practicing physicians in
      Massachusetts. Participants were asked if they had encountered discrimination,
      how significant the discrimination was against a specific group, the frequency of
      personal discrimination, and the type of discrimination. Factor analysis
      identified four types of discrimination: career advancement, punitive behaviors,
      practice barriers and hiring barriers. RESULTS: A total of 445 responses were
      received (a 24% response rate). Sixty-three percent of responding physicians had
      experienced some form of discrimination. Respondents were women (46%),
      racial/ethnic minorities (42%) and international medical graduates (IMGs) (40%).
      In addition, 26% of those classified as white were also IMGs. Over 60% of
      respondents believed discrimination against IMGs was very or somewhat
      significant. Almost 27% of males acknowledged that gender bias against females
      was very or somewhat significant. IMGs were more likely to indicate that
      discrimination against IMGs was significant in their current organization. Of
      U.S. medical graduates (USMGs) 44% reported that discrimination against IMGs in
      their current organization was significant. Nonwhites were more likely to report
      that discrimination based on race/ethnicity was significant. Nearly 29% of white
      respondents also believed that such discrimination was very or somewhat
      significant. CONCLUSIONS: Physicians practicing in academic, research, and
      private practice sectors experience discrimination based on gender,
      ethnic/racial, and IMG status.

PMID- 15868768
TI  - Mental health, family function and obesity in African-American women.
AB  - CONTEXT: African-American women are disproportionately affected by obesity and
      its related diseases. How psychological and psychosocial factors that affect this
      population differ across weight categories remains poorly understood. PURPOSE: To
      determine whether poor mental health and family functioning are associated with
      obesity in African-American women. METHODS: African-American women patients aged
      21-65 years were interviewed at three primary care centers. Four well-established
      assessment tools were used to measure general mental and physical health status,
      family functioning, depressive symptoms and anxiety levels. Demographics, health
      behaviors and family and personal histories of overweight were assessed. RESULTS:
      Among 113 patients, after controlling for age and parity, obese women had
      significantly higher anxiety levels, poorer perception of their physical health,
      more often were overweight as a child, had overweight parents or siblings and
      experienced more psychosocial problems in their family growing up, compared to
      overweight and normal weight women. CONCLUSIONS: The observed findings of poor
      mental health, perception of physical health and family function in obese African
      American women support a need for clinical attention and further study.

PMID- 15868769
TI  - Medicaid managed care: disparities in the use of thiazolidinediones compared with
      metformin.
AB  - OBJECTIVE: To identify patient characteristics that are associated with the
      incidence of thiadolidinediones (TZDs) or metformin prescnbing in Medicaid
      managed care plans. RESEARCH DESIGN AND METHODS: We utilized a retrospective
      cohort study design. Two-and-one-half years of prescription claims of Medicaid
      managed care organizations (MCOs) patients who were new utilizers of metformin or
      TZDs were analyzed using univariate, bivariate and multivariate models.
      Multivariate logistic regression models were built to assess the combined effect
      of all variables on the likelihood of incident use of TZDs or metformin. RESULTS:
      Claims for 3,041 patients were analyzed for the period between January 15, 2000
      and June 15, 2002. African Americans and urban residents were less likely to be
      started on TZDs (OR = 0.678, 95% C1 = 0.830-1.206; OR = 0.579, 95% CI = 0.479
      0.699, respectively). Advanced age, preexisting comorbidities and diabetes
      complications, and prior use of other oral diabetes drugs or insulin were
      predictors of increased likelihood of TZD initiation. CONCLUSIONS: Race, age,
      residential setting, preexisting comorbidities and diabetes complications, other
      oral diabetes drug use, and insulin use are statistically significant predictors
      of initial prescribing of TZD or metformin in a Medicaid MCO population. Findings
      can potentially inform the management of diabetes in managed care so as to
      improve outcomes.

PMID- 15868770
TI  - Racial and ethnic variations in office-based medical care for work-related
      injuries and illnesses.
AB  - OBJECTIVES: This exploratory study uses nationally representative data to
      evaluate the extent to which ambulatory care for work-related conditions varies
      by patients' race and ethnicity. METHODS: Using the National Ambulatory Medical
      Care Survey (NAMCS) for 1997 and 1998, we describe medical care for work-related
      conditions, stratifying by whether the patient self-identified as African
      American, white, Hispanic and/or non-Hispanic. Multivariate regression analyses
      were conducted to evaluate the impact of patient race and ethnicity on care,
      controlling for age, gender, geographical region and MSA (urban/rural) status.
      RESULTS: Compared to white patients, African-American patients were more likely
      to receive mental health counseling and physical therapy and less likely to see a
      nurse, after controlling for age, gender, geographical region and MSA status.
      Hispanic patients were more likely to receive x-rays and need insurer
      authorization for care and less likely to receive a prescription drug or to see a
      physician, compared to non-Hispanics. CONCLUSIONS: This is the nation's first
      study to describe socially based differences in medical care provided for
      patients with work-related injuries and illnesses. Identifying areas in which
      these variations in care exist is a critical first step in ensuring that
      equitable care is afforded to all injured workers.

PMID- 15868771
TI  - Helicobacter pylori eradication has no effect on metabolic and inflammatory
      parameters.
AB  - BACKGROUND: An increased risk in coronary heart disease associated with
      Helicobacter pylori (H. pylon) appears to be partially mediated by modifications
      of the atherogenic lipoprotein and inflammatory parameters. We conducted a
      controlled trial aimed at evaluating the changes of metabolic and inflammatory
      parameters after H. pylon eradication. METHODS: We included in the study 169
      patients with H. pylori infection and conducted a retrospective longitudinal
      survey of 87 subjects (76 men, 11 women) who received treatment for H. pylon
      eradication and 82 control subjects (63 men, 19 women) who did not receive
      treatment. We compared pre- and posteradication (one year after) the metabolic
      and inflammatory parameters, such as blood sugar, lipid profiles, insulin
      resistance, white blood cell count and C-reactive protein. RESULTS: No
      significant changes from the baseline in metabolic and inflammatory parameters
      within each group were observed. Changes in the serum levels of metabolic and
      inflammatory parameters were similar between the two groups. CONCLUSIONS:
      Metabolic and inflammatory parameters, including blood sugar, lipid profiles,
      insulin resistance, white blood cell count and C-reactive protein, were not
      changed after H. pylori eradication treatment. H. pylori eradication has no
      effect on metabolic and inflammatory parameters.

PMID- 15868772
TI  - The utility of the environmental scan for public health practice: lessons from an
      urban program to increase cancer screening.
AB  - The environmental scan is a tool that can be utilized to collect data to design
      health programs uniquely tailored to the needs of communities. However, it
      remains relatively undefined, unevaluated and underutilized in the field of
      public health. While individual studies indicate the utility of the environmental
      scan for public health, it is difficult to find a theoretical framework or
      guidelines on how to design, implement or evaluate the process within public
      health practice. The purpose of this study was to elicit lessons learned to
      maximize the utility of the environmental scan as a tool for public health. This
      process occurred through the development and implementation of an environmental
      scan as part of the needs-assessment phase of a project to increase cancer
      screening among African Americans in Baltimore, MD. Data collection methods for
      the environmental scan included a review of community stakeholders, cancer
      incidence and community assets and liabilities in target communities, focus-group
      sessions and key informant interviews with service providers. The environmental
      scan was conducted in 2003 and allowed for rapid acquisition and use of
      information about events, trends and relationships in the neighborhoods targeted
      for our project and enabled researchers to move forward with implementing the
      cancer-screening project. The researchers conclude that the environmental scan
      has considerable potential to be a creative, responsive, cost-effective and
      mobilizing tool for public health practice. However, further application and
      critical review are necessary to make it a more effective public health tool and
      an established research methodology.

PMID- 15868773
TI  - Use of complementary and alternative medical therapies among racial and ethnic
      minority adults: results from the 2002 National Health Interview Survey.
AB  - PURPOSE: Complementary and alternative medicine (CAM) use among ethnic minority
      populations is poorly understood. We sought to examine CAM use in Hispanics, non
      Hispanic blacks and non-Hispanic whites. METHODS: We analyzed data from the
      Alternative Health Supplement to the 2002 National Health Interview Survey
      (NHIS), including information on 19 different CAM therapies used in the past 12
      months. RESULTS: An estimated 34% of Hispanic, non-Hispanic black and non
      Hispanic white adults in the United States used at least one CAM therapy
      (excluding prayer) during the prior 12 months (2002). CAM use was highest for non
      Hispanic whites (36%), followed by Hispanics (27%) and non-Hispanic blacks (26%).
      Non-Hispanic whites were more likely to use herbal medicine, relaxation
      techniques and chiropractic more frequently than Hispanics and non-Hispanic
      blacks. After controlling for other sociodemographic factors, Hispanic and non
      Hispanic black races/ethnicities were associated with less CAM use, with adjusted
      odds ratios (95% confidence intervals) of 0.78 (0.70, 0.87) and 0.71 (0.65,
      0.78), respectively. Hispanics cited using CAM because conventional medical
      treatments were too expensive more frequently than non-Hispanic blacks or whites.
      Hispanics had the highest provider nondisclosure rates (68.5%), followed by non
      Hispanic blacks (65.1%) and non-Hispanic whites (58.1%). CONCLUSIONS: Excluding
      prayer, Hispanics and non-Hispanic blacks used CAM less frequently than non
      Hispanic whites and were less likely to disclose their use to their healthcare
      provider. Further research is needed to improve our understanding of the
      disparities in CAM use.

PMID- 15868774
TI  - Differences in posttraumatic stress disorder symptoms between elderly non
      Hispanic Whites and African Americans.
AB  - This study was a secondary analysis of two similar data sets to examine potential
      differences in PTSD symptoms between elderly whites and African Americans (n=90).
      Without regard to trauma type, there were no differences between the races in the
      distribution of PTSD diagnosis or specific symptom constellations (e.g., re
      experiencing, avoidance, or arousal). No significant differences were yielded for
      individuals who experienced a physical trauma. However, in cases of nonphysical
      trauma, elderly whites were significantly more likely than elderly African
      Americans to report hyperarousal symptoms. These results suggest the need to
      better understand coping strategies used by whites and African Americans in the
      face of trauma.

PMID- 15868775
TI  - A further examination of the "epidemiologic paradox": birth outcomes among
      Latinas.
AB  - PURPOSE: Low rates of low birthweight (LBW) among foreign-born Latinas of low
      socioeconomic status have been called the "epidemiologic paradox." This study
      examined the extent to which the paradox can be explained by differential
      distribution of risk factors. PROCEDURES: The data source was the 1996-1997 New
      York City Birth File with 78,364 singleton births to Latinas. Ancestries included
      Colombians, Dominicans, Ecuadorians, Mexicans, Puerto Ricans and other Hispanics.
      First, a logistic regression was used to predict a LBW birth with ancestry and
      birthplace as the only independent variables. Demographic, medical and behavioral
      risks were added in subsequent regression models. FINDINGS: The LBW rate for the
      sample was 6.8%, with significant differences between birthplace subgroups and
      among ancestries. Puerto Ricans had the highest LBW rates, 9.1% for the mainland
      born and 9.2% for the island-born. In separate regressions for six ancestry
      groups, birthplace was a significant predictor of LBW only among Mexicans and
      other Hispanics. CONCLUSION: In this population-based study of Latina women in
      New York City, the positive birth outcomes of foreign-born women are largely due
      to their more favorable distribution of behavioral risk factors. The
      "epidemiologic paradox" does not account for the LBW rates among Puerto Ricans in
      New York City, a high percentage of whom are mainland-born (73.4%). Compared to
      other Latinas, Puerto Rican women are likely to have experienced far more years
      of acculturation, which can result in negative health behaviors.

PMID- 15868776
TI  - Demographic and clinical correlates of metabolic syndrome in Native African type
      2 diabetic patients.
AB  - OBJECTIVES: To describe the metabolic syndrome and its demographic and clinical
      correlates in native African type-2 diabetic patients. METHODS: Cross-sectional
      analysis of 254 type-2 diabetic indigenous Nigerians consecutively recruited in a
      teaching hospital. The main outcome measure was metabolic syndrome. Variables of
      interest included family history/duration of diabetes mellitus and hypertension,
      gender, socioeconomic class, occupation and place of domicile (urban or rural).
      Intergroup comparisons were made with Chi-squared tests or t-tests. RESULTS:
      Patients were aged 35-80 years (mean: 52.0 +/- 11.7 years) and made of 154
      (60.6%) males and 100 (39.4%) females. Full-blown metabolic syndrome was noted in
      52 patients (20.5%). Metabolic syndrome, as defined by the WHO, was noted in 150
      patients (59.1%). About 72.4% of patients were dyslipidemic, 54.3% were
      hypertensive, 42.5% were obese, 44.9% were microalbuminuric and 32.3% were
      hyperuricemic. Ischemic heart disease (myocardial infarction) occurred in only
      2.4% of patients. Concurrent hypertension and dyslipidemia; obesity and
      dyslipidemia; and hypertension and obesity occurred in 44.4%, 42.5% and 33.1% of
      type-2 diabetics, respectively. Compared to the diabetics without metabolic
      syndrome, those with the syndrome had a significantly higher proportion of
      patients with a family history of hypertension and diabetes (44% versus 25%; p =
      0.003); among the upper/middle socioeconomic class: 52.0% versus 30.8% (p =
      0.001); and among the urban dwelling: 68.0% versus 49.0% (p = 0.004). Metabolic
      syndrome was inversely proportional to the physical activity of an individual
      (chi2 = 21.69, df = 5, p = 0.001). Blood pressure was significantly higher among
      patients with metabolic syndrome than those without it (140.6 +/- 22.9/85.2 +/-
      12.9 mmHg versus 126.9 +/- 15.4 mmHg; P < 0.01). CONCLUSIONS: The development of
      metabolic syndrome in African type-2 diabetic patients is influenced by
      demographic and clinical factors. Vigilant dietary habit and physical exercise
      may reduce the chance of metabolic syndrome in urban Nigerian type-2 diabetics.

PMID- 15868777
TI  - Misrepresentations of the Tuskegee Study of Untreated Syphilis.
AB  - The Tuskegee Study of Untreated Syphilis (TSUS) is the subject of medical
      research, healthcare, ethics, race relations and fictitious media portrayals
      (e.g., movie, play). Unraveling misrepresentations about the TSUS is important
      because prevailing views continue to contribute to alleged mistrust of the
      medical system by the black community and compromised doctor-patient and
      researcher-participant relationships. A comparative analysis of standard TSUS
      information was conducted and included evidenced-based alternative information in
      an effort to: (a) contextualize the TSUS with accurate medical, public health and
      historical information and (b) balance claims of racism, nontreatment and denial
      of treatment. An article in the Winter 2003 Radcliffe Quarterly misrepresented
      the images of two historical African-American health institutions, the John A.
      Andrew Memorial Hospital and the Tuskegee Veterans Administration Hospital. A
      critical analysis challenges these pictorial misrepresentations and documents, in
      part, a continuing and prevailing pattern of biased misrepresentations in
      discussions about the TSUS. The National Medical Association (NMA) and the
      Journal of the National Medical Association have a history of advocacy for
      African-American health, a record of combating racial discrimination and a quest
      for truth about the status of the black community. As past NMA historical
      notables have performed through their advancement, service and leadership, health
      professionals now have the opportunity, obligation and information to educate the
      American community about the TSUS with evidenced-based information.

PMID- 15868778
TI  - Dairy report one-sided: dairy products contribute to cancer risks.

PMID- 15868779
TI  - Ventricular diastolic function study has shortcomings.

PMID- 15868780
TI  - Neurobiology of managing perceived stress.

PMID- 15868781
TI  - Approaching health equity.

PMID- 15868782
TI  - Effect of microcomputed tomography voxel size on the finite element model
      accuracy for human cancellous bone.
AB  - The level of structural detail that can be acquired and incorporated in a finite
      element (FE) analysis might greatly influence the results of microcomputed
      tomography (microCT)-based FE simulations, especially when relatively large
      bones, such as whole vertebrae, are of concern. We evaluated the effect of
      scanning and reconstruction voxel size on the microCT-based FE analyses of human
      cancellous tissue samples for fixed- and free-end boundary conditions using
      different combinations of scan/reconstruction voxel size. We found that the bone
      volume fraction (BV/TV) did not differ considerably between images scanned at 21
      and 50 microm and reconstructed at 21, 50, or 110 microm (-0.5% to 7.8% change
      from the 21/21 microm case). For the images scanned and reconstructed at 110
      microm, however, there was a large increase in BV/TV compared to the 21/21 microm
      case (58.7%). Fixed-end boundary conditions resulted in 1.8% [coefficient of
      variation (COV)] to 14.6% (E) difference from the free-end case. Dependence of
      model output parameters on scanning and reconstruction voxel size was similar
      between free- and fixed-end simulations. Up to 26%, 30%, 17.8%, and 32.3%
      difference in modulus (E), and average (VMExp), standard deviation (VMSD) and
      coefficient of variation (COV) of von Mises stresses, respectively, was observed
      between the 21/21 microm case and other scan/reconstruction combinations within
      the same (free or fixed) simulation group. Observed differences were largely
      attributable to scanning resolution, although reconstruction resolution also
      contributed significantly at the largest voxel sizes. All 21/21 microm results
      (taken as the gold standard) could be predicted from the 21/50 (r2adj= 0.91
      0.99;p<0.001), 21/110 (r2adj =0.58-0.99;p<0.02) and 50/50 results (r2adj=0.61
      0.97;p<0.02). While BV/TV, VMSD, and VMExp/sigma(z) from the 21/21 could be
      predicted by those from the 50/110 (r2adj =0.63-0.93;p<0.02) and 110/110 (r2adj
      =0.41-0.77;p<0.05) simulations as well, prediction of E, VMExp, and COV became
      marginally significant (0.04<p<0.13) at 50/110 and nonsignificant at 110/110
      (0.21<p<0.70). In conclusion, calculation of cancellous bone modulus, mean
      trabecular stress, and other parameters are subject to large errors at 110/110
      microm voxel size. However, enough microstructural details for studying bone
      volume fraction, trabecular shear stress scatter, and trabecular shear stress
      amplification (VMExp/sigma(z)) can be resolved using a 21/110 microm, 50/110
      microm, and 110/110 microm voxels for both free- and fixed-end constraints.

PMID- 15868783
TI  - Finite element prediction of proximal femoral fracture patterns under different
      loads.
AB  - The main purpose of this work is to discuss the ability of finite element
      analyses, together with an appropriate anisotropic fracture criterion, to predict
      the ultimate load and type of fracture in bones and more specifically in the
      proximal femur. We show here that the use of a three-dimensional anisotropic
      criterion provides better results than other well-known isotropic criteria. The
      criterion parameters and the anisotropic elastic properties were defined in terms
      of the bone tissue microstructure, quantified by the apparent density and the so
      called "fabric tensor", whose spatial distributions were obtained by means of an
      anisotropic remodeling model able to capture the main features of the internal
      structure of long bones. In order to check the validity of the results obtained,
      they have been compared with those of an experimental work that analyzes
      different types of fractures induced in the proximal femur by a static overload.

PMID- 15868784
TI  - Material properties of the human lumbar facet joint capsule.
AB  - The human facet joint capsule is one of the structures in the lumbar spine that
      constrains motions of vertebrae during global spine loading (e.g., physiological
      flexion). Computational models of the spine have not been able to include
      accurate nonlinear and viscoelastic material properties, as they have not
      previously been measured. Capsules were tested using a uniaxial ramp-hold
      protocol or a haversine displacement protocol using a commercially available
      materials testing device. Plane strain was measured optically. Capsules were
      tested both parallel and perpendicular to the dominant orientation of the
      collagen fibers in the capsules. Viscoelastic material properties were
      determined. Parallel to the dominant orientation of the collagen fibers, the
      complex modulus of elasticity was E*=1.63MPa, with a storage modulus of
      E'=1.25MPa and a loss modulus of: E" =0.39MPa. The mean stress relaxation rates
      for static and dynamic loading were best fit with first-order polynomials:
      B(epsilon) = 0.1110epsilon-0.0733 and B(epsilon)= -0.1249epsilon + 0.0190,
      respectively. Perpendicular to the collagen fiber orientation, the viscous and
      elastic secant moduli were 1.81 and 1.00 MPa, respectively. The mean stress
      relaxation rate for static loading was best fit with a first-order polynomial: B
      (epsilon) = -0.04epsilon - 0.06. Capsule strength parallel and perpendicular to
      collagen fiber orientation was 1.90 and 0.95 MPa, respectively, and extensibility
      was 0.65 and 0.60, respectively. Poisson's ratio parallel and perpendicular to
      fiber orientation was 0.299 and 0.488, respectively. The elasticity moduli were
      nonlinear and anisotropic, and capsule strength was larger aligned parallel to
      the collagen fibers. The phase lag between stress and strain increased with
      haversine frequency, but the storage modulus remained large relative to the
      complex modulus. The stress relaxation rate was strain dependent parallel to the
      collagen fibers, but was strain independent perpendicularly.

PMID- 15868785
TI  - Mechanical properties of laser cut poly(L-lactide) micro-specimens: implications
      for stent design, manufacture, and sterilization.
AB  - BACKGROUND: The development of endoluminal stents from polymeric materials
      requires an understanding of the basic mechanical properties of the polymer and
      the effects of manufacturing and sterilization on those properties. METHODS: Pure
      poly(L-lactide) (PLLA) and PLLA containing varying amounts of triethylcitrate
      (TEC) as a plasticizer (5-10-15%) were studied. The specimens were solution-cast
      and CO2 laser-cut. Specimen dimensions were adapted to the strut size of
      polymeric vascular stents. The properties of the PLLA micro-specimens were
      assessed before and after sterilization (EtO cold gas, H2O2-plasma, beta- and
      gamma-irradiation). Tensile tests, and creep and recovery tests were carried out
      at 37 degrees C. Additionally the thermal and thermo-mechanical characteristics
      were investigated using dynamic-mechanical analysis (DMA) and differential
      scanning calorimetry (DSC). RESULTS: The results showed the dramatic influence of
      the plasticizer content and sterilization procedure on the mechanical properties
      of the material. Laser cutting had a lesser effect. Hence the effects of
      processing and sterilization must not be overlooked in the material selection and
      design phases of the development process leading to clinical use. Altogether, the
      results of these studies provide a clearer understanding of the complex
      interaction between the laser machining process and terminal sterilization on the
      primary mechanical properties of PLLA and PLLA plasticized with TEC.

PMID- 15868786
TI  - Study of SARS transmission via liquid droplets in air.
AB  - Microscale liquid droplets could act as the SARS carriers in air when released
      from an infected person through breathing, coughing, or sneezing. In this study,
      a dynamic model has been built to quantitatively investigate the effect of the
      relative humidity on the transport of liquid-droplets in air using coupled mass
      transfer and momentum equations. Under higher relative humidity, the exhaled
      liquid droplets evaporate slowly. Larger droplets fall faster, which could reduce
      the probability of the droplets inhalation. This may be one of the most important
      factors that influence the SARS transmission in air.

PMID- 15868787
TI  - The flow field downstream of an oscillating collapsed tube.
AB  - A two-component laser Doppler anemometer was used to determine the velocity of
      aqueous flow in the region from 0.25 to 2.5 diameters downstream of a collapsible
      tube while the tube was executing vigorous repetitive flow-induced oscillations.
      The Reynolds number for the time-averaged flow was 10,750. A simultaneous
      measurement of the pressure at the downstream end of the tube was used to align
      all the results in time at sixty locations in each of the two principal planes
      defined by the axes of collapse of the flexible tube upstream. The raw data of
      seed-particle velocity were used to create a periodic waveform for each measured
      velocity component at each location by least-squares fitting of a Fourier series.
      The results are presented as both velocity vectors and interpolated contours, for
      each of ten salient instants during the cycle of oscillation. In the plane of the
      collapse major axis, the dominant feature is the jet which emerges from each of
      the two tube lobes when it collapses, but transient retrograde flow is observed
      on both the central and lateral edges of this jet. In the orthogonal, minor-axis
      plane, the dominant feature is the retrograde flow, which during part of the
      cycle extends over the whole plane. All these features are essentially confined
      to the first 1.5 diameters of the rigid pipe downstream of the flexible tube.
      These data map the temporal and spatial extent of the highly three-dimensional
      reversing flow just downstream of an oscillating collapsed tube.

PMID- 15868788
TI  - A mathematical model of alveolar gas exchange in partial liquid ventilation.
AB  - In partial liquid ventilation (PLV), perfluorocarbon (PFC) acts as a diffusion
      barrier to gas transport in the alveolar space since the diffusivities of oxygen
      and carbon dioxide in this medium are four orders of magnitude lower than in air.
      Therefore convection in the PFC layer resulting from the oscillatory motions of
      the alveolar sac during ventilation can significantly affect gas transport. For
      example, a typical value of the Peclet number in air ventilation is Pe
      approximately 0.01, whereas in PLV it is Pe approximately 20. To study the
      importance of convection, a single terminal alveolar sac is modeled as an
      oscillating spherical shell with gas, PFC, tissue and capillary blood
      compartments. Differential equations describing mass conservation within each
      compartment are derived and solved to obtain time periodic partial pressures.
      Significant partial pressure gradients in the PFC layer and partial pressure
      differences between the capillary and gas compartments (P(C)-Pg) are found to
      exist. Because Pe>> 1, temporal phase differences are found to exist between P(C)
      Pg and the ventilatory cycle that cannot be adequately described by existing non
      convective models of gas exchange in PLV The mass transfer rate is nearly
      constant throughout the breath when Pe>>1, but when Pe<<1 nearly 100% of the
      transport occurs during inspiration. A range of respiratory rates (RR), including
      those relevant to high frequency oscillation (HFO) +PLV, tidal volumes (V(T)) and
      perfusion rates are studied to determine the effect of heterogeneous
      distributions of ventilation and perfusion on gas exchange. The largest changes
      in P(C)O2 and P(C)CO2 occur at normal and low perfusion rates respectively as RR
      and V(T) are varied. At a given ventilation rate, a low RR-high V(T) combination
      results in higher P(C)O2, lower P(C)CO2 and lower (P(C)-Pg) than a high RR-low
      V(T) one.

PMID- 15868789
TI  - Mathematical model for pressure losses in the hemodialysis graft vascular
      circuit.
AB  - Stenosis-induced thrombosis and abandonment of the hemodialysis synthetic graft
      is an important cause of morbidity and mortality. The graft vascular circuit is a
      unique low-resistance shunt that has not yet been systematically evaluated. In
      this study, we developed a mathematical model of this circuit. Pressure losses
      (deltaPs) were measured in an in vitro experimental apparatus and compared with
      losses predicted by equations from the engineering literature. We considered the
      inflow artery, arterial and venous anastomoses, graft, stenosis, and outflow
      vein. We found significant differences between equations and experimental
      results, and attributed these differences to the transitional nature of the flow.
      Adjustment of the equations led to good agreement with experimental data. The
      resulting mathematical model predicts relations between stenosis, blood flow,
      intragraft pressure, and important clinical variables such as mean arterial blood
      pressure and hematocrit. Application of the model should improve understanding of
      the hemodynamics of the stenotic graft vascular circuit.

PMID- 15868790
TI  - Bioheat and mass transfer as viewed through a microscope.

PMID- 15868791
TI  - Thermal damage prediction for collagenous tissues part I: a clinically relevant
      numerical simulation incorporating heating rate dependent denaturation.
AB  - Subablative thermotherapy is frequently used for the treatment of joint
      instability related diseases. In this therapy, mechanically deformed collagenous
      tissues are thermally shrunk and the stability of the tissue is re-established.
      In this research, the thermal damage fields generated by three different clinical
      heating modalities (monopolar and bipolar radio frequency and Ho:YAG laser) are
      compared numerically using finite element analysis. The heating rate dependent
      denaturation characteristics of collagenous tissues are incorporated into the
      model using experimental data from in vitro experimentation with rabbit patellar
      tendons. It is shown that there are significant differences among the thermal
      damage profiles created by these modalities, explaining the main reason for the
      discrepancies reported in the literature in terms of the efficacy and safety of
      each modality. In the complementary paper, the accuracy of the model presented
      here is verified by in vitro experimentation with a model collagenous tissue and
      by quantifying the denaturation-induced birefringence change using Optical
      Coherence Tomography and Magnetic Resonance Imaging.

PMID- 15868792
TI  - Determining dual Euler angles of the ankle complex in vivo using "flock of birds"
      electromagnetic tracking device.
AB  - The dual Euler angles method has been proposed as an alternative approach to
      describe the general spatial human joint motion. In this study, the dual Euler
      angles method was applied to study the three-dimensional motion of the ankle
      complex. The methodology for obtaining dual Euler angles of the ankle complex was
      developed by using a "Flock of Birds" electromagnetic tracking device. The
      repeatability of the methodology was studied based on the intertester and
      intratester variability analysis. Finally kinematic coupling characteristics of
      the ankle complex during dorsiflexion-plantarflexion, eversion-inversion, and
      abduction-adduction were analyzed according to the parameters of the dual Euler
      angles.

PMID- 15868793
TI  - Sudden loading during a dynamic lifting task: a simulation study.
AB  - It is believed that nurses risk the development of back pain as a consequence of
      sudden loadings during tasks in which they are handling patients. Forward
      dynamics simulations of sudden loads (applied to the arms) during dynamic lifting
      tasks were performed on a two-dimensional whole-body model. Loads were in the
      range of -80 kg to 80 kg, with the initial load being 20 kg. Loading the arm
      downwards with less than that which equals a mass of 20 kg did not change the
      compressive forces on the spine when compared to a normal lifting motion with a
      20 kg mass in the hands. However when larger loads (40 kg to 80 kg extra in the
      hands) were simulated, the compressive forces exceeded 13,000 N (above 3400 N is
      generally considered a risk factor). Loading upwards led to a decrease in the
      compressive forces but to a larger backwards velocity at the end of the movement.
      In the present study, it was possible to simulate a fast lifting motion. The
      results showed that when loading the arms downwards with a force that equals 40
      kg or more, the spine was severely compressed. When loading in the opposite
      direction (unloading), the spine was not compressed more than during a normal
      lifting motion. In practical terms, this indicates that if a nursing aide tries
      to catch a patient who is falling, large compressive forces are applied to the
      spine.

PMID- 15868794
TI  - Virtual slope control of a forward dynamic bipedal walker.
AB  - Active joint torques are the primary source of power and control in dynamic
      walking motion. However the amplitude, rate, timing and phasic behavior of the
      joint torques necessary to achieve a natural and stable performance are difficult
      to establish. The goal of this study was to demonstrate the feasibility and
      stable behavior of an actively controlled bipedal walking simulation wherein the
      natural system dynamics were preserved by an active, nonlinear, state-feedback
      controller patterned after passive downhill walking. A two degree-of-freedom,
      forward-dynamic simulation was implemented with active joint torques applied at
      the hip joints and stance leg ankle. Kinematic trajectories produced by the
      active walker were similar to passive dynamic walking with active joint torques
      influenced by prescribed walking velocity. The control resulted in stable steady
      state gait patterns, i.e. eigenvalue magnitudes of the stride function were less
      than one. The controller coefficient analogous to the virtual slope was modified
      to successfully control average walking velocity. Furture developments are
      necessary to expand the range of walking velocities.

PMID- 15868795
TI  - Simulating dynamic activities using a five-axis knee simulator.
AB  - This work describes the design and capabilities of the Purdue Knee Simulator:
      Mark II and a sagittal-plane model of the machine. This five-axis simulator was
      designed and constructed to simulate dynamic loading activities on either
      cadaveric knee specimens or total knee prostheses mounted on fixtures. The
      purpose of the machine was to provide a consistent, realistic loading of the knee
      joint, allowing the kinematics and specific loading of the structures of the knee
      to be determined based on condition, articular geometry, and simulated activity.
      The sagittal-plane model of the knee simulator was developed both to predict the
      loading at the knee from arbitrary inputs and to generate the necessary inputs
      required to duplicate specified joint loading. Measured tibio-femoral compressive
      force and quadriceps tension were shown to be in good agreement with the
      predicted loads from the model. A controlled moment about the ankle-flexion axis
      was also shown to change the loading on the quadriceps.

PMID- 15868796
TI  - The relationship of normal and abnormal microstructural proliferation to the
      mitral valve closure sound.
AB  - BACKGROUND: Many diseases that affect the mitral valve are accompanied by the
      proliferation or degradation of tissue microstructure. The early acoustic
      detection of these changes may lead to the better management of mitral valve
      disease. In this study, we examine the nonstationary acoustic effects of
      perturbing material parameters that characterize mitral valve tissue in terms of
      its microstructural components. Specifically, we examine the influence of the
      volume fraction, stiffness and splay of collagen fibers as well as the stiffness
      of the nonlinear matrix in which they are embedded. METHODS AND RESULTS: To model
      the transient vibrations of the mitral valve apparatus bathed in a blood medium,
      we have constructed a dynamic nonlinear fluid-coupled finite element model of the
      valve leaflets and chordae tendinae. The material behavior for the leaflets is
      based on an experimentally derived structural constitutive equation. The gross
      movement and small-scale acoustic vibrations of the valvular structures result
      from the application of physiologic pressure loads. Material changes that
      preserved the anisotropy of the valve leaflets were found to preserve valvular
      function. By contrast, material changes that altered the anisotropy of the valve
      were found to profoundly alter valvular function. These changes were manifest in
      the acoustic signatures of the valve closure sounds. Abnormally, stiffened valves
      closed more slowly and were accompanied by lower peak frequencies. CONCLUSION:
      The relationship between stiffness and frequency, though never documented in a
      native mitral valve, has been an axiom of heart sounds research. We find that the
      relationship is more subtle and that increases in stiffness may lead to either
      increases or decreases in peak frequency depending on their relationship to
      valvular function.

PMID- 15868797
TI  - Method and apparatus for soft tissue material parameter estimation using tissue
      tagged Magnetic Resonance Imaging.
AB  - We describe an experimental method and apparatus for the estimation of
      constitutive parameters of soft tissue using Magnetic Resonance Imaging (MRI), in
      particular for the estimation of passive myocardial material properties. MRI
      tissue tagged images were acquired with simultaneous pressure recordings, while
      the tissue was cyclically deformed using a custom built reciprocating pump
      actuator A continuous three-dimensional (3D) displacement field was reconstructed
      from the imaged tag motion. Cavity volume changes and local tissue microstructure
      were determined from phase contrast velocity and diffusion tensor MR images,
      respectively. The Finite Element Method (FEM) was used to solve the finite
      elasticity problem and obtain the displacement field that satisfied the applied
      boundary conditions and a given set of material parameters. The material
      parameters which best fit the FEM predicted displacements to the displacements
      reconstructed from the tagged images were found by nonlinear optimization. The
      equipment and method were validated using inflation of a deformable silicon gel
      phantom in the shape of a cylindrical annulus. The silicon gel was well described
      by a neo-Hookian material law with a single material parameter C1=8.71+/-0.06kPa,
      estimated independently using a rotational shear apparatus. The MRI derived
      parameter was allowed to vary regionally and was estimated as C1 =8.80+/-0.86kPa
      across the model. Preliminary results from the passive inflation of an isolated
      arrested pig heart are also presented, demonstrating the feasibility of the
      apparatus and method for isolated heart preparations. FEM based models can
      therefore estimate constitutive parameters accurately and reliably from MRI
      tagging data.

PMID- 15868798
TI  - A comparison between mechano-electrochemical and biphasic swelling theories for
      soft hydrated tissues.
AB  - Biological tissues like intervertebral discs and articular cartilage primarily
      consist of interstitial fluid, collagen fibrils and negatively charged
      proteoglycans. Due to the fixed charges of the proteoglycans, the total ion
      concentration inside the tissue is higher than in the surrounding synovial fluid
      (cation concentration is higher and the anion concentration is lower). This
      excess of ion particles leads to an osmotic pressure difference, which causes
      swelling of the tissue. In the last decade several mechano-electrochemical
      models, which include this mechanism, have been developed. As these models are
      complex and computationally expensive, it is only possible to analyze
      geometrically relatively small problems. Furthermore, there is still no
      commercial finite element tool that includes such a mechano-electrochemical
      theory. Lanir (Biorheology, 24, pp. 173-187, 1987) hypothesized that electrolyte
      flux in articular cartilage can be neglected in mechanical studies. Lanir's
      hypothesis implies that the swelling behavior of cartilage is only determined by
      deformation of the solid and by fluid flow. Hence, the response could be
      described by adding a deformation-dependent pressure term to the standard
      biphasic equations. Based on this theory we developed a biphasic swelling model.
      The goal of the study was to test Lanir's hypothesis for a range of material
      properties. We compared the deformation behavior predicted by the biphasic
      swelling model and a full mechano-electrochemical model for confined compression
      and 1D swelling. It was shown that, depending on the material properties, the
      biphasic swelling model behaves largely the same as the mechano-electrochemical
      model, with regard to stresses and strains in the tissue following either
      mechanical or chemical perturbations. Hence, the biphasic swelling model could be
      an alternative for the more complex mechano-electrochemical model, in those cases
      where the ion flux itself is not the subject of the study. We propose thumbrules
      to estimate the correlation between the two models for specific problems.

PMID- 15868799
TI  - Changes in the mechanical environment of stenotic arteries during interaction
      with stents: computational assessment of parametric stent designs.
AB  - Clinical studies have identified factors such as the stent design and the
      deployment technique that are one cause for the success or failure of angioplasty
      treatments. In addition, the success rate may also depend on the stenosis type.
      Hence, for a particular stenotic artery, the optimal intervention can only be
      identified by studying the influence of factors such as stent type, strut
      thickness, geometry of the stent cell, and stent-artery radial mismatch with the
      wall. We propose a methodology that allows a set of stent parameters to be
      varied, with the aim of evaluating the difference in the mechanical environment
      within the wall before and after angioplasty with stenting. Novel scalar
      quantities attempt to characterize the wall changes inform of the contact
      pressure caused by the stent struts, and the stresses within the individual
      components of the wall caused by the stent. These quantities are derived
      numerically and serve as indicators, which allow the determination of the correct
      size and type of the stent for each individual stenosis. In addition, the luminal
      change due to angioplasty may be computed as well. The methodology is
      demonstrated by using a full three-dimensional geometrical model of a postmortem
      specimen of a human iliac artery with a stenosis using imaging data. To describe
      the material behavior of the artery, we considered mechanical data of eight
      different vascular tissues, which formed the stenosis. The constitutive models
      for the tissue components capture the typical anisotropic, nonlinear and
      dissipative characteristics under supra-physiological loading conditions. Three
      dimensional stent models were parametrized in such a way as to enable new designs
      to be generated simply with regard to variations in their geometric structure.
      For the three-dimensional stent-artery interaction we use a contact algorithm
      based on smooth contact surfaces of at least C-continuity, which prevents
      numerical problems known from standard facet-based contact algorithm. The
      proposed methodology has the potential to provide a scientific basis for
      optimizing treatment procedures and stent geometries and materials, to help stent
      designers examine new stent designs "virtually," and to assist clinicians in
      choosing the most suitable stent for a particular stenosis.

PMID- 15868800
TI  - Influence of decorin and biglycan on mechanical properties of multiple tendons in
      knockout mice.
AB  - Evaluations of tendon mechanical behavior based on biochemical and structural
      arrangement have implications for designing tendon specific treatment modalities
      or replacement strategies. In addition to the well studied type I collagen, other
      important constituents of tendon are the small proteoglycans (PGs). PGs have been
      shown to vary in concentration within differently loaded areas of tendon,
      implicating them in specific tendon function. This study measured the mechanical
      properties of multiple tendon tissues from normal mice and from mice with knock
      outs of the PGs decorin or biglycan. Tail tendon fascicles, patellar tendons
      (PT), and flexor digitorum longus tendons (FDL), three tissues representing
      different in vivo loading environments, were characterized from the three groups
      of mice. It was hypothesized that the absence of decorin or biglycan would have
      individual effects on each type of tendon tissue. Surprisingly, no change in
      mechanical properties was observed for the tail tendon fascicles due to the PG
      knockouts. The loss of decorin affected the PT causing an increase in modulus and
      stress relaxation, but had little effect on the FDL. Conversely, the loss of
      biglycan did not significantly affect the PT, but caused a reduction in both the
      maximum stress and modulus of the FDL. These results give mechanical support to
      previous biochemical data that tendons likely are uniquely tailored to their
      specific location and function. Variances such as those presented here need to be
      further characterized and taken into account when designing therapies or
      replacements for any one particular tendon.

PMID- 15868801
TI  - Influence of cervical disc degeneration after posterior surgical techniques in
      combined flexion-extension--a nonlinear analytical study.
AB  - Laminectomy and facetectomy are surgical techniques used for decompression of the
      cervical spinal stenosis. Recent in vitro and finite element studies have shown
      significant cervical spinal instability after performing these surgical
      techniques. However, the influence of degenerated cervical disk on the
      biomechanical responses of the cervical spine after these surgical techniques
      remains unknown. Therefore, a three-dimensional nonlinear finite element model of
      the human cervical spine (C2-C7) was created. Two types of disk degeneration
      grades were simulated. For each grade of disk degeneration, the intact as well as
      the two surgically altered models simulating C5 laminectomy with or without C5-C6
      total facetectomies were exercised under flexion and extension. Intersegmental
      rotational motions, internal disk annulus, cancellous and cortical bone stresses
      were obtained and compared to the normal intact model. Results showed that the
      cervical rotational motion decreases with progressive disk degeneration.
      Decreases in the rotational motion due to disk degeneration were accompanied by
      higher cancellous and cortical bone stress. The surgically altered model showed
      significant increases in the rotational motions after laminectomies and
      facetectomies when compared to the intact model. However, the percentage
      increases in the rotational motions after various surgical techniques were
      reduced with progressive disk degeneration.

PMID- 15868802
TI  - Simultaneous measurement of three-dimensional joint kinematics and ligament
      strains with optical methods.
AB  - The objective of this study was to assess the precision and accuracy of a
      nonproprietary, optical three-dimensional (3D) motion analysis system for the
      simultaneous measurement of soft tissue strains and joint kinematics. The system
      consisted of two high-resolution digital cameras and software for calculating the
      3D coordinates of contrast markers. System precision was assessed by examining
      the variation in the coordinates of static markers over time. Three-dimensional
      strain measurement accuracy was assessed by moving contrast markers fixed
      distances in the field of view and calculating the error in predicted strain.
      Three-dimensional accuracy for kinematic measurements was assessed by simulating
      the measurements that are required for recording knee kinematics. The field of
      view (190 mm) was chosen to allow simultaneous recording of markers for soft
      tissue strain measurement and knee joint kinematics. Average system precision was
      between +/-0.004 mm and +/-0.035 mm, depending on marker size and camera angle.
      Absolute error in strain measurement varied from a minimum of +/-0.025% to a
      maximum of +/-0.142%, depending on the angle between cameras and the direction of
      strain with respect to the camera axes. Kinematic accuracy for translations was
      between +/-0.008 mm and +/-0.034 mm, while rotational accuracy was +/-0.082 deg
      to +/-0.160 deg. These results demonstrate that simultaneous optical measurement
      of 3D soft tissue strain and 3D joint kinematics can be performed while achieving
      excellent accuracy for both sets of measurements.

PMID- 15868803
TI  - Trabecular bone contributes to strength of the proximal femur under mediolateral
      impact in the avian.
AB  - BACKGROUND: Osteoporosis in long bones involves loss of cortical thickness and of
      the trabecular microarchitecture. Deterioration and weakening of trabecular bone
      tissue during osteoporosis imposes greater physiological loads on the cortical
      shell. However, it is unclear whether trabecular bone significantly contributes
      to the strength of whole bones under non-physiological impact loads. METHOD OF
      APPROACH: We hypothesize that trabecular tissue in epiphyses of long bones
      contributes to resisting and distributing impact loads. To test this hypothesis,
      we caused artificial trabecular bone loss in proximal femora of adult hens but
      did not alter the bone cortex. Subsequently, we compared the energy required to
      fracture the proximal part of femora with missing trabecular tissue with the
      energy required to fracture control femora, by means of a Charpy test. RESULTS:
      Extensive loss of trabecular bone in hens (over 0.50 grams or approximately 71%
      weight fraction) significantly reduced the energy required to fracture the whole
      proximal femur in mediolateral impacts (from approximately 0.37 joule in controls
      to approximately 0.20 joule after extraction of core trabecular tissue).
      CONCLUSIONS: These findings indicate that trabecular bone in the proximal femur
      is important for distributing impact loads applied to the cortex, and support the
      concept that in treating osteoporosis to prevent hip fractures, it is just as
      important to prevent trabecular bone loss as it is important to prevent loss of
      cortical thickness.

PMID- 15868804
TI  - Single-step stereolithography of complex anatomical models for optical flow
      measurements.
AB  - Transparent stereolithographic rapid prototyping (RP) technology has already
      demonstrated in literature to be a practical model construction tool for optical
      flow measurements such as digital particle image velocimetry (DPIV), laser
      doppler velocimetry (LDV), and flow visualization. Here, we employ recently
      available transparent RP resins and eliminate time-consuming casting and chemical
      curing steps from the traditional approach. This note details our methodology
      with relevant material properties and highlights its advantages.
      Stereolithographic model printing with our procedure is now a direct single-step
      process, enabling faster geometric replication of complex computational fluid
      dynamics (CFD) models for exact experimental validation studies. This methodology
      is specifically applied to the in vitro flow modeling of patient-specific total
      cavopulmonary connection (TCPC) morphologies. The effect of RP machining grooves,
      surface quality, and hydrodynamic performance measurements as compared with the
      smooth glass models are also quantified.

PMID- 15868805
TI  - Deep neck space infection: still a challenge to pediatricians.

PMID- 15868806
TI  - Cholelithiasis and pseudocholelithiasis in childhood.

PMID- 15868807
TI  - Deep neck infection in children.
AB  - OBJECTIVES: Deep neck infection is a potentially life-threatening disease and
      rarely seen in children. Because of the obscure complaints and symptoms, the
      diagnosis of deep neck infection may be delayed, which may result in
      inappropriate treatment. This retrospective study was aimed at analyzing the
      occurrence of complications, diagnostic methods and proper managements of deep
      neck infection in children. METHODS: A retrospective study was performed on 30
      children with deep neck infection treated from October 1999 through October 2003.
      The etiology, clinical symptoms, laboratory examination, radiological
      examination, bacteriology, and treatments were retrospectively analyzed. RESULTS:
      The most common predisposing factors were tonsillitis and upper respiratory tract
      infection. The most common symptoms were fever (93.3%) and painful swelling of
      the neck (70.0%). Both peritonsillar (24.3%) and parapharyngeal space infections
      (24.3%) were the most common, followed by submandibular space infections (18.9%).
      The most common pathogens isolated were Staphylococcus aureus (27.3%) and
      viridans streptococci (22.7%). The mean duration of hospitalization was 7.9 days,
      with a range from 2 to 18 days. Complications occurred in 2 patients, including
      recurrence and pulmonary edema. CONCLUSIONS: Deep neck infection should be
      suspected in a child who presents with fever and painful swelling of the neck.
      Staphylococcus aureus and viridans streptococci were the most common pathogens.
      Computed tomography scan should be performed in time and infections in
      peritonsillar and ,parapharyngeal spaces were the most common.

PMID- 15868808
TI  - Cholelithiasis in Down syndrome.
AB  - Cholelithiasis in infants, children and adolescents is rare, with a prevalence
      rate of less than 0.5%. The aim of this study was to determine the association
      between Down syndrome (DS) and cholelithiasis. We conducted a prospective,
      controlled study on 51 subjects (age range 11-20 years old) to assess the risk
      factors of cholelithiasis in children and adolescents with Down syndrome. The
      subjects recruited in the study consisted of 51 children with Down syndrome and
      253 children in the control group. There was no statistical difference in gender
      and age between the DS and control groups. Gallstone disease was detected in 2
      females, aged 17 and 19 years old, respectively. None had cholelithiasis in the
      control group. The result showed that children with DS had significantly higher
      prevalence of cholelithiasis (3.92%) compared with controls (0%) (p < 0.01). The
      overall prevalence of overweight and obesity in DS group was 83%, which was
      significantly higher than 20% in the control group (p < 0.01). Chromosome anomaly
      and overweight were two significant risk factors for cholelithiasis. Clinicians
      should be aware of increased risk of cholelithiasis in children with DS.

PMID- 15868810
TI  - Outcome of vocal cord paralysis in infants.
AB  - Although laryngomalacia is the leading cause of stridor in infancy, vocal cord
      paralysis, despite its low incidence, is still the second most common cause.
      However, the etiology of infant vocal cord paralysis is different from that of
      adults, and the management protocol is controversial. Therefore, we conducted
      this study to better characterize the cause and outcome of vocal cord paralysis
      in infants. From January 1997 to December 2003, we treated thirteen infants
      younger than one year for vocal cord paralysis. Seven infants were idiopathic
      (idiopathic group), two might be caused by prior surgery (iatrogenic group), two
      might be caused by central neuropathy (neurological group), and two were born
      after difficult delivery (obstetrical group). In the idiopathic group, six
      infants spontaneously recovered and one infant had right-side recovery, but the
      left side was still paralytic. All infants in the iatrogenic and obstetrical
      groups spontaneously recovered. However, no infant in the neurological group
      recovered. Spontaneous recovery occurred in 76.9% of affected infants. More than
      half (70%) of these spontaneous recoveries occurred within 6 months. In our
      experience, direct flexible laryngoscopy is mandatory for all infants younger
      than one year of age presenting with stridor. Except for extreme infants (e. g.
      bilateral vocal cord paralysis with severe respiratory distress and central
      neuropathy) who require a temporary tracheotomy to relieve the airway
      obstruction, we recommend waiting for at least 6 months before proceeding to
      invasive surgical interventions.

PMID- 15868809
TI  - Adrenoleukodystrophy: clinical analysis of 9 Taiwanese children.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder and identified in
      many races without apparent predilection for any race. This study was designed to
      investigate the clinical and therapeutic aspects of X-ALD in Taiwanese children
      with this disorder. We retrospectively reviewed all children admitted to NTUH
      from Nov. 1993 to Aug. 2002 with the diagnosis of ALD, defined by increased very
      long chain fatty acid (VLCFA). The mean age at diagnosis of the patients was 7.4
      years (range, 2.8 to 13 years). Seven out of 9 patients had abnormal brain
      magnetic resonance image (MRI) studies. Three patients received bone marrow
      transplantation. Of these, two died of severe graft-versus-host disease and the
      other remained stable. Of the remaining 6 patients, two patients were in
      vegetative status and the other two patients were neurologically normal. X-ALD in
      Taiwanese children had similar clinical manifestations as reviewed in western
      countries. Symmetrical demyelination in parieto-occipital region and the
      accumulation of contrast material at the edge of the lesion are the typical MRI
      findings. Proton MR spectroscopy (MRS) can be used to evaluate either the
      asymptomatic patient or patient with normal brain image. Performance of T-cell
      depletion bone marrow transplantation or cord blood transplantation is suggested
      for X-ALD with early cerebral involvement.

PMID- 15868811
TI  - Cat-scratch disease in children at a medical center.
AB  - BACKGROUND: Cat-scratch disease (CSD) is a well-recognized, benign, self-limited
      regional lymphadenopathy occurring in immunocompetent patients. Several
      retrospective studies have demonstrated that CSD occurs at all ages, however, the
      disease appears to be more common in children. We conducted a retrospective case
      study of CSD in children presenting at our hospital, and reviewed the relevant
      literature. METHODS: The medical records for eight children (age range 4-13
      years) diagnosed with cat-scratch disease at the Tri-service General Hospital in
      Taipei from September 1, 1986 to September 1, 2002 were retrospectively reviewed.
      Clinical manifestations, diagnostic methods, and treatment types were assessed.
      RESULTS: The male gender predominated (75%); the median age was 8.6 years. The
      latency period ranged from 7 days to 1 month, with a median diagnostic interval
      of 8.5 days. There were no deaths. All patients had lymphadenopathy, and the
      axillary node was the most prevalent site (62.5%). The most common locations for
      the scratch or inoculation lesions were the hands and/or fingers (62.5%). Three
      patients were diagnosed from clinical symptoms and history (37.5%), three from
      serological study (37.5 %), and two using biopsy or aspiration (25%). All
      patients were given antibiotic treatment. The most commonly used antibiotic was
      gentamicin (75%), with the average duration of treatment 8.7 days. The average
      hospital stay was 8 days, with the lymph-node size reduced relative to
      pretreatment baseline in all except one case. CONCLUSION: In our experience, the
      long-term prognosis for children with typical CSD is favorable, and gentamicin
      may be a good antibiotic option.

PMID- 15868812
TI  - An early diagnosis leads to a good prognosis: a patient with maple syrup urine
      disease--screened by tandem mass spectrometry.
AB  - Maple syrup urine disease (MSUD), or branched-chain ketoaciduria, is an autosomal
      recessive disorder of branched-chain amino acid metabolism. The classic MSUD is
      the most severe form. The prognosis is usually guarded. The acute metabolic
      decompensation and neurological deterioration attribute to severe sequelae. The
      age of diagnosis and subsequent metabolic control are the most important
      determinants of long-term prognosis. We report one classic MSUD case with good
      outcome. The early diagnosis was achieved by tandem mass spectrometry screening.
      Since most MSUD patients in Taiwan are native Taiwanese, we strongly suggest
      routine tandem mass screening of MSUD is necessary, especially in the high-risk
      groups, to minimize morbidity and mortality.

PMID- 15868813
TI  - Ceftriaxone-associated gallbladder pseudolithiasis: report of one case.
AB  - Ceftriaxone is known to induce reversible precipitates in the gallbladders of
      adults and children. However, ceftriaxone-associated gallbladder pseudolithiasis
      in children is rarely reported in Taiwan. We report a case of 5-year-old boy with
      Salmonella gastroenteritis, who was treated with ceftriaxone due to multidrug
      resistance and severe course. Cholelithiasis developed five days after initiation
      of ceftriaxone therapy and completely resolved one month after the end of
      treatment. Pediatricians and radiologists must be aware of this complication to
      prevent anxiety and unnecessary cholecystectomy.

PMID- 15868814
TI  - Mycoplasma pneumoniae infection associated with hemolytic anemia--report of one
      case.
AB  - Immune hemolytic anemia is a rare condition in childhood. Cold agglutinins have
      been implicated in the etiology of the hemolysis. However, cold agglutinins may
      occur in various infections, such as mycoplasma pneumoniae and infectious
      mononucleosis. In children, especially of preschool age, mycoplasma pneumoniae
      very commonly cause respiratory tract infection, but inducing an immune hemolytic
      anemia is exceptional. We present here a case of cold agglutinin-related severe
      hemolytic anemia (Hb = 3.8 gm/dl) secondary to mycoplasma pneumoniae infection
      who recovered completely after blood transfusion, intravenous immunoglobulin
      (IVIG) and medical treatment with erythromycin. It is suggested that even though
      very rare, mycoplasma pneumoniae may induce the occurrence of cold agglutinins
      and cause immune hemolytic anemia.

PMID- 15868815
TI  - Cerebral infarction associated with possible enteroviral infection in an infant.
AB  - Enterovirus infection has been rarely reported to cause cerebral infarction in
      infants. We describe a 2-month-old boy with right focal seizure and right
      hemiparesis associated with enterovirus infection during an epidemic of
      enterovirus 71 infection in Taiwan in 1998. Magnetic resonance imaging and
      angiography showed vasculitis in the left anterior cerebral artery with cerebral
      infarction. In the unclarified pathogenesis of cerebral disease in enterovirus
      infection, this case suggests focal vasculitis with subsequent cerebral
      infarction. Enterovirus-related vasculitis of the central nervous system is thus
      another consideration when facing a child with focal seizure, acute hemiplegia
      and cerebral infarction.

PMID- 15868816
TI  - An overlooked association of brachial plexus palsy: diaphragmatic paralysis.
AB  - Diaphragmatic paralysis in newborns is related to brachial plexus palsy. It can
      be overlooked if thorough examination isn't done. We present a two-weeks-old baby
      with a birth weight of 3800 grams who had a left-sided brachial plexus palsy and
      torticollis with an undiagnosed left diaphragmatic paralysis even though he was
      examined by different physicians several times. The role of physical examination,
      the chest x-rays of patients with brachial paralysis and the treatment modalities
      of diaphragmatic paralysis due to obstetrical factors are discussed.

PMID- 15868817
TI  - Facility profile. Addition overcomes construction obstacles.

PMID- 15868818
TI  - Data-driven design. Infrastructure challenges of the IT revolution.

PMID- 15868819
TI  - Risk + reward. Decision analysis for health facility managers.

PMID- 15868820
TI  - Security, stat! ED safety requires cooperation between departments.

PMID- 15868821
TI  - The ED challenge: designing for excellence.

PMID- 15868822
TI  - Goal tending: patient safety and the environment of care.

PMID- 15868823
TI  - Hard facts: maintaining concrete floors in health care facilities.

PMID- 15868824
TI  - Signed distance computation using the angle weighted pseudonormal.
AB  - The normals of closed, smooth surfaces have long been used to determine whether a
      point is inside or outside such a surface. It is tempting to also use this method
      for polyhedra represented as triangle meshes. Unfortunately, this is not possible
      since, at the vertices and edges of a triangle mesh, the surface is not C1
      continuous, hence, the normal is undefined at these loci. In this paper, we
      undertake to show that the angle weighted pseudonormal (originally proposed by
      Thurmer and Wuthrich and independently by Sequin) has the important property that
      it allows us to discriminate between points that are inside and points that are
      outside a mesh, regardless of whether a mesh vertex, edge, or face is the closest
      feature. This inside-outside information is usually represented as the sign in
      the signed distance to the mesh. In effect, our result shows that this sign can
      be computed as an integral part of the distance computation. Moreover, it
      provides an additional argument in favor of the angle weighted pseudonormals
      being the natural extension of the face normals. Apart from the theoretical
      results, we also propose a simple and efficient algorithm for computing the
      signed distance to a closed C0 mesh. Experiments indicate that the sign
      computation overhead when running this algorithm is almost negligible.

PMID- 15868825
TI  - Registration based on projective reconstruction technique for augmented reality
      systems.
AB  - In AR systems, registration is one of the most difficult problems currently
      limiting their application. In this paper, we propose a simple registration
      method using projective reconstruction. This method consists of two steps:
      embedding and tracking. Embedding involves specifying four points to build the
      world coordinate system on which a virtual object will be superimposed. In
      tracking, a projective reconstruction technique is used to track these four
      specified points to compute the model view transformation for augmentation. This
      method is simple, as only four points need to be specified at the embedding stage
      and the virtual object can then be easily augmented onto a real scene from a
      video sequence. In addition, it can be extended to a scenario using the
      projective matrix that has been obtained from previous registration results using
      the same AR system. The proposed method has three advantages: 1) It is fast
      because the linear least square method can be used to estimate the related matrix
      in the algorithm and it is not necessary to calculate the fundamental matrix in
      the extended case. 2) A virtual object can still be superimposed on a related
      area even if some parts of the specified area are occluded during the whole
      process. 3) This method is robust because it remains effective even when not all
      the reference points are detected during the whole process, as long as at least
      six pairs of related reference points correspondences can be found. Some
      experiments have been conducted to validate the performance of the proposed
      method.

PMID- 15868826
TI  - A method to generate soft shadows using a layered depth image and warping.
AB  - We present an image-based method for propagating area light illumination through
      a Layered Depth Image (LDI) to generate soft shadows from opaque and
      nonrefractive transparent objects. In our approach, using the depth peeling
      technique, we render an LDI from a reference light sample on a planar light
      source. Light illumination of all pixels in an LDI is then determined for all the
      other sample points via warping, an image-based rendering technique, which
      approximates ray tracing in our method. We use an image-warping equation and
      McMillan's warp ordering algorithm to find the intersections between rays and
      polygons and to find the order of intersections. Experiments for opaque and
      nonrefractive transparent objects are presented. Results indicate our approach
      generates soft shadows fast and effectively. Advantages and disadvantages of the
      proposed method are also discussed.

PMID- 15868827
TI  - An intelligent system approach to higher-dimensional classification of volume
      data.
AB  - In volume data visualization, the classification step is used to determine voxel
      visibility and is usually carried out through the interactive editing of a
      transfer function that defines a mapping between voxel value and color/opacity.
      This approach is limited by the difficulties in working effectively in the
      transfer function space beyond two dimensions. We present a new approach to the
      volume classification problem which couples machine learning and a painting
      metaphor to allow more sophisticated classification in an intuitive manner. The
      user works in the volume data space by directly painting on sample slices of the
      volume and the painted voxels are used in an iterative training process. The
      trained system can then classify the entire volume. Both classification and
      rendering can be hardware accelerated, providing immediate visual feedback as
      painting progresses. Such an intelligent system approach enables the user to
      perform classification in a much higher dimensional space without explicitly
      specifying the mapping for every dimension used. Furthermore, the trained system
      for one data set may be reused to classify other data sets with similar
      characteristics.

PMID- 15868828
TI  - Hardware-assisted visibility sorting for unstructured volume rendering.
AB  - Harvesting the power of modern graphics hardware to solve the complex problem of
      real-time rendering of large unstructured meshes is a major research goal in the
      volume visualization community. While, for regular grids, texture-based
      techniques are well-suited for current GPUs, the steps necessary for rendering
      unstructured meshes are not so easily mapped to current hardware. We propose a
      novel volume rendering technique that simplifies the CPU-based processing and
      shifts much of the sorting burden to the GPU, where it can be performed more
      efficiently. Our hardware-assisted visibility sorting algorithm is a hybrid
      technique that operates in both object-space and image-space. In object-space,
      the algorithm performs a partial sort of the 3D primitives in preparation for
      rasterization. The goal of the partial sort is to create a list of primitives
      that generate fragments in nearly sorted order. In image-space, the fragment
      stream is incrementally sorted using a fixed-depth sorting network. In our
      algorithm, the object-space work is performed by the CPU and the fragment-level
      sorting is done completely on the GPU. A prototype implementation of the
      algorithm demonstrates that the fragment-level sorting achieves rendering rates
      of between one and six million tetrahedral cells per second on an ATI Radeon
      9800.

PMID- 15868829
TI  - Reflectance from images: a model-based approach for human faces.
AB  - In this paper, we present an image-based framework that acquires the reflectance
      properties of a human face. A range scan of the face is not required. Based on a
      morphable face model, the system estimates the 3D shape and establishes point-to
      point correspondence across images taken from different viewpoints and across
      different individuals' faces. This provides a common parameterization of all
      reconstructed surfaces that can be used to compare and transfer BRDF data between
      different faces. Shape estimation from images compensates deformations of the
      face during the measurement process, such as facial expressions. In the common
      parameterization, regions of homogeneous materials on the face surface can be
      defined a priori. We apply analytical BRDF models to express the reflectance
      properties of each region and we estimate their parameters in a least-squares fit
      from the image data. For each of the surface points, the diffuse component of the
      BRDF is locally refined, which provides high detail. We present results for
      multiple analytical BRDF models, rendered at novel orientations and lighting
      conditions.

PMID- 15868830
TI  - Uniform remeshing with an adaptive domain: a new scheme for view-dependent level
      of-detail rendering of meshes.
AB  - We present a new algorithm for view-dependent level-of-detail rendering of
      meshes. Not only can it effectively resolve complex geometry features similar to
      edge collapse-based schemes, but it also produces meshes that modern graphics
      hardware can render efficiently. This is accomplished through a novel hybrid
      approach: For each frame, we view-dependently refine the progressive mesh (PM)
      representation of the original mesh and use the output as the base domain of
      uniform regular refinements. The algorithm exploits frame-to-frame coherence and
      only updates portions of the output mesh corresponding to modified domain
      triangles. The PM representation is built using a custom volume preservation
      based error function. A simple k-d tree enhanced jump-and-walk scheme is used to
      quickly map from the dynamic base domain to the original mesh during regular
      refinements. In practice, the PM refinement provides a view-optimized base domain
      for later regular refinements. The regular refinements ensure almost-everywhere
      regularity of output meshes, allowing optimization for vertex cache coherence and
      caching of geometry data in high-performance graphics memory. Combined, they also
      have the effect of allowing our algorithm to operate on uniform clusters of
      triangles instead of individual ones, reducing CPU workload.

PMID- 15868831
TI  - Creating and simulating skeletal muscle from the visible human data set.
AB  - Simulation of the musculoskeletal system has important applications in
      biomechanics, biomedical engineering, surgery simulation, and computer graphics.
      The accuracy of the muscle, bone, and tendon geometry as well as the accuracy of
      muscle and tendon dynamic deformation are of paramount importance in all these
      applications. We present a framework for extracting and simulating high
      resolution musculoskeletal geometry from the segmented visible human data set. We
      simulate 30 contact/collision coupled muscles in the upper limb and describe a
      computationally tractable implementation using an embedded mesh framework. Muscle
      geometry is embedded in a nonmanifold, connectivity preserving simulation mesh
      molded out of a lower resolution BCC lattice containing identical, well-shaped
      elements, leading to a relaxed time step restriction for stability and, thus,
      reduced computational cost. The muscles are endowed with a transversely
      isotropic, quasi-incompressible constitutive model that incorporates muscle fiber
      fields as well as passive and active components. The simulation takes advantage
      of a new robust finite element technique that handles both degenerate and
      inverted tetrahedra.

PMID- 15868832
TI  - Dynamic interaction between deformable surfaces and nonsmooth objects.
AB  - In this paper, we introduce new techniques that enhance the computational
      performance for the interactions between sharp objects and deformable surfaces.
      The new formulation is based on a time-domain predictor-corrector model. For this
      purpose, we define a new kind of (pi, beta, I)-surface. The partitioning of a
      deformable surface into a finite set of (pi, beta, I)-surfaces allows us to prune
      a large number of noncolliding feature pairs. This leads to a significant
      performance improvement in the collision detection process. The intrinsic
      collision detection is performed in the time domain. Although it is more
      expensive compared to the static interference test, it avoids portions of the
      surfaces passing through each other in a single time step. In order to resolve
      all the possible collision events at a given time, a penetration-free motion
      space is constructed for each colliding particle. By keeping the velocity of each
      particle inside the motion space, we guarantee that the current colliding feature
      pairs will not penetrate each other in the subsequent motion. A static analysis
      approach is adopted to handle friction by considering the forces acting on the
      particles and their velocities. In our formulation, we further reduce the
      computational complexity by eliminating the need to compute repulsive forces.

PMID- 15868833
TI  - Creating speech-synchronized animation.
AB  - We present a facial model designed primarily to support animated speech. Our
      facial model takes facial geometry as input and transforms it into a parametric
      deformable model. The facial model uses a muscle-based parameterization, allowing
      for easier integration between speech synchrony and facial expressions. Our
      facial model has a highly deformable lip model that is grafted onto the input
      facial geometry to provide the necessary geometric complexity needed for creating
      lip shapes and high-quality renderings. Our facial model also includes a highly
      deformable tongue model that can represent the shapes the tongue undergoes during
      speech. We add teeth, gums, and upper palate geometry to complete the inner
      mouth. To decrease the processing time, we hierarchically deform the facial
      surface. We also present a method to animate the facial model over time to create
      animated speech using a model of coarticulation that blends visemes together
      using dominance functions. We treat visemes as a dynamic shaping of the vocal
      tract by describing visemes as curves instead of keyframes. We show the utility
      of the techniques described in this paper by implementing them in a text-to
      audiovisual-speech system that creates animation of speech from unrestricted
      text. The facial and coarticulation models must first be interactively
      initialized. The system then automatically creates accurate real-time animated
      speech from the input text. It is capable of cheaply producing tremendous amounts
      of animated speech with very low resource requirements.

PMID- 15868834
TI  - Disrupting normalcy: lesbian, gay, queer issues and mental health. An
      introduction.

PMID- 15868835
TI  - Internalized homophobia: a factor in depression, anxiety, and suicide in the gay
      and lesbian population.
AB  - Two-hundred and twenty participants recruited through multiple sampling
      strategies completed a self-report questionnaire examining: (a) whether
      internalized homophobia predicts depressive and anxious symptoms, suicide, and
      substance abuse; and (b) the periods of gay-identity development which were
      particularly risky for suicide. Results indicate that internalized homophobia,
      particularly negative feelings towards one's own homosexuality (as measured by
      the Self subscale of the Nungesser Homosexual Attitudes Inventory), accounts for
      18% of the variance in depressive scores and 13% of anxiety scores (using the
      Beck inventories). Internalized homophobia did not predict suicide independently
      from depression. The period of greatest risk for both suicidal ideation and
      suicide attempts was the period of disclosure of one's homosexuality to one's
      immediate family.

PMID- 15868836
TI  - Lesbian survivors of childhood sexual abuse: community, identity, and resilience.
AB  - Adult lesbian survivers of childood sexual abuse were interviewed using grounded
      and structured methods to explore the interaction between being, or coming out
      as, a lesbian and healing from childhood sexual abuse (CSA). A history of CSA was
      found to render coming out as a lesbian more complicated and often more
      difficult. Having or developing a lesbian identity caused significant changes in
      respondents' social support networks and spiritual beliefs and communities,
      afforded many opportunities for greater healing, and in the balance seemed to
      facilitate the healing process. Implications for program planning and service
      delivery are briefly discussed.

PMID- 15868838
TI  - Addressing the needs of lesbian, gay, bisexual, transgendered, queer, and
      questioning clients within university psychiatric services: reflections and
      recommendations.
AB  - Concerns still exist among lesbian-, gay-, bisexual-, transgendered-, and queer
      identified individuals (LGBTQ individuals) about their reception and treatment by
      psychiatric service providers. The Psychiatric Service at the University of
      Toronto and the Office of LGBTQ Resources and Programs convened a committee to
      address expanding the capacities of the Service related to the needs of LGBTQ and
      questioning students. In this paper, we describe the committee's role,
      initiatives, and successes and discuss challenges encountered in the process. The
      model of community development drawn from in this work can be adapted for use in
      other community health settings.

PMID- 15868837
TI  - Questioning and sexual minority adolescents: high school experiences of bullying,
      sexual harassment and physical abuse.
AB  - Using a subset of youth from a sample of 3,636 Canadian adolescents, the present
      study examined sexual orientation and victimization experiences in high school. A
      total of 130 adolescents indicated they were gay, lesbian, bisexual, or
      questioning their sexual orientation. Significantly more adolescents identified
      as bisexual (N = 50) or questioning (N = 68) than as gay or lesbian (N = 12).
      Sexual-minority and questioning youth were more likely than heterosexual youth to
      be victims of bullying, peer sexual harassment, and peer or dating-partner
      physical abuse. Implications of victimization on questioning and sexual-minority
      adolescents' mental health are discussed.

PMID- 15868839
TI  - Transforming schools of social work into spaces of social action: a critical
      exploration of Project Interaction, The Gay, Lesbian, Bisexual and Two-Spirit
      Initiative of McGill University's School of Social Work.
AB  - This article examines the question of how universities can be encouraged to
      address the mental health concerns of GLBT-SQ people and communities from a
      perspective of solidarity. In so doing, the authors take a case study approach,
      using Project Interaction: The Gay, Lesbian, Bisexual and Two-Spirit Initiative
      of McGill University's School of Social Work, to critically reflect upon the
      challenges arising from the development of an alternative organization within
      academia. The purpose of this reflection is to highlight how normal operations at
      work on university campuses, and within health and allied health curriculum, can
      be disrupted with the goal of providing momentum for the creation of affirmative
      space, the advancement of educational initiatives, and the building of
      opportunities for social change.

PMID- 15868840
TI  - [Elderly women, invisible lesbians].
AB  - The social invisibility of aging lesbians is a major obstacle to the adaptation
      of residential services to their needs. After looking at the difficulties
      associated with aging among lesbians, this article examines social mechanisms
      that reproduce their invisibility. Findings are based on a qualitative analysis
      of two series of interviews, 10 with service providers in private residences for
      older people and 10 with aging lesbians. On one side, there is openness at the
      level of personal attitudes, but proactive commitment in residence management and
      knowledge about older lesbians' psychosocial needs are lacking. On the other
      side, aging lesbians perceive residences as an environment where they would not
      feel secure enough to be open about their sexual orientation.

PMID- 15868841
TI  - Lesbian health and the assumption of heterosexuality: an organizational
      perspective.
AB  - This study used a qualitative research design to explore hospital policies and
      practices and the assumption of female heterosexuality. The assumption of
      heterosexuality is a product of discursive practices that normalize
      heterosexuality and individualize lesbian sexual identities. Literature indicates
      that the assumption of female heterosexuality is implicated in both the
      invisibility and marked visibility of lesbians as service users. This research
      adds to existing literature by shifting the focus of study from individual to
      organizational practices and, in so doing, seeks to uncover hidden truths,
      explore the functional power of language, and allow for the discovery of what we
      know and--equally as important--how we know.

PMID- 15868842
TI  - [Domestic violence in lesbians: the experience of a community group in Quebec].
AB  - Intervention and research in same-sex relationship domestic violence is a newly
      emerging field. The Groupe d'intervention en violence conjugale chez les
      lesbiennes (GIVCL) is the first francophone community organization in Quebec to
      provide support for lesbians who are victims of domestic violence. Realizing that
      there were very few resources and services adapted to the specific needs of
      lesbians, the GIVCL provides support groups for victims, offers training
      sessions, and participates in research in this area. The GIVCL seeks to share its
      experience and concerns with other groups. This article outlines the GIVCL's
      program, discusses the growth and limitations of the program, and suggests
      approaches that can lead to the development of services that are better adapted
      to the needs of the lesbian community.

PMID- 15868843
TI  - Pretty, witty and white: disrupting hetero-normalcy and reinventing privilege on
      Queer as Folk.

PMID- 15868844
TI  - Urinary tract infection in children: incidence of vesicoureteral reflux, imaging
      studies, and antimicrobial resistance among E. coli.

PMID- 15868845
TI  - No association of urokinase gene 3'-UTR polymorphism with bronchopulmonary
      dysplasia for ventilated preterm infants.
AB  - Pathological findings pertaining to bronchopulmonary dysplasia (BPD) are
      consistent with a process of prolonged lung inflammation and impaired healing.
      The balance of the competing activities of coagulation and fibrinolysis may
      contribute to the premature lung's response to acute injury. We investigated the
      association of the urokinase gene polymorphism with BPD in ventilated preterm
      infants whose gestational age was below 30 weeks. BPD is defined as infants
      remaining dependent upon active respiratory support and/or oxygen supplementation
      and featuring characteristic radiographic changes in the lung fields on the 28th
      postnatal day (BPD-28d) and at a corrected age of 36 weeks of gestation (BPD
      36w). Two hundred and four ventilated preterm infants were enrolled in the study.
      The typing of each specific genotype polymorphism was performed by polymerase
      chain reaction (PCR) and restriction analysis. Perinatal risk factors for BPD,
      genotype distribution, and allelic frequencies were compared between infants
      suffering from BPD (28-d), BPD (36-w) and their respective ventilated preterm
      infants who did not develop BPD infants. The genotype proportions of the
      urokinase 3'-UTR polymorphism for BPD (28-d), BPD (36-w) and their respective
      ventilated preterm infants who did not develop BPD did not differ significantly.
      There was no difference in allelic frequency for the urokinase 3'-UTR
      polymorphism between BPD (28-d), BPD (36-w) and their respective ventilated
      preterm infants who did not develop BPD infants. We concluded that urokinase gene
      3'-UTR C/T polymorphism is not a suitable marker for predicting susceptibility
      and severity to BPD for preterm infants of Taiwanese.

PMID- 15868846
TI  - Phenylalanine hydroxylase deficiency: intelligence of patients after early
      dietary treatment.
AB  - Neonatal screening for hyperphenylalaninemia (HPA) has been performed in Taiwan
      for more than 20 years. In this paper, we studied 21 cases of HPA caused by
      phenylalanine hydroxylase (PAH) deficiency. These patients were detected by a
      single newborn screening center over ten-years, and the incidence was one in
      63,690. According to the initial plasma phenylalanine levels, four of the 21
      patients belonged to classical phenylketonuria (PKU), seven were mild PKU, and
      ten were mild HPA. They commenced diet control at the age of 47 +/- 22 (17-106)
      days. Fourteen patients completed IQ tests, three of the 14 patients having
      classical PKU, five having mild PKU, and six having mild HPA. Their average IQ
      scores were within normal ranges (full-scale IQ 98 +/- 14, verbal IQ 92 +/- 8,
      and performance IQ 104 +/- 19), but patients with classical PKU tended to have
      lower IQ scores than other patients. Since classical PKU is rare in Taiwan,
      further studies including detailed neuropsychological tests will be required to
      evaluate the effect of treatment in this group of patients.

PMID- 15868847
TI  - Subclavian central venous catheterization in infants with body weight less than
      10 kg.
AB  - Central venous access is an important aspect of medical treatment in intensive
      care units. We frequently require central venous catheterization (CVC) for total
      parenteral nutrition (TPN), intravenous antibiotics, multiple transfusions, and
      chemotherapy. The primary aim of this study is to demonstrate that percutaneous
      central venous catheterization in patients with body weight (BW) less than 10 kg
      can be conducted by the subclavian vein rather than the traditional femoral vein.
      Between January 1998 and December 2003, we performed 70 subclavian vein
      catheterizations (SVCs) in 46 patients with BW less than 10 kg in the pediatric
      intensive care unit (PICU) of a tertiary medical center. We divided patients
      according to their body weight into two groups, BW less than 5 kg and BW between
      5 and 10 kg. We found SVC had a high total success rate, 92.9% (65/70), for the
      whole group. Success rate was 83.3% (15/18) for the BW less than 5 kg group and
      96.2% (50/52) for the BW 5-10 kg group. In this study we found percutaneous
      subclavian venous catheterization in children with BW below 10 kg to be a
      relatively safe procedure with low risk of complication and no risk of mortality.

PMID- 15868848
TI  - Childhood urinary tract infection: a clinical analysis of 597 cases.
AB  - OBJECTIVES OF STUDY: To gain new insights into the epidemiology, genitourinary
      (GU) tract anomalies, etiologies, susceptibility of urinary pathogens to
      antibiotics in children with urinary tract infection (UTI) during the past decade
      in Taiwan. MATERIALS AND METHODS: By reviewing medical charts for patients
      admitted to Kaohsiung Veterans General Hospital between January 1995 and December
      2003, we identified and enrolled patients 14 years of age or less admitted due to
      UTI that was confirmed by positive urine culture. RESULTS: A total of 597
      patients made up our sample. Sixty-eight percent of patients were 1 year old or
      younger. Boys predominated infant cohort (68.1%). Twenty-seven point one percent
      of the patients were found in urinalysis to have 5 white blood cells or fewer per
      high power field and 17.6% had positive nitrite reaction. The pathogens were
      Escherichia coli, the most common (74.7%), followed by Proteus spp. (6.7%), and
      Klebsiella spp. (6.4%). E. coli was resistant to ampicillin in 82.0% of the
      cases, followed by sulfamethoxazole/trimethoprim (55.2%), gentamicin (24.9%), and
      cefazolin (24%). Resistance to ampicillin and sulfamethoxazole/trimethoprim
      tended to increase year by year. Forty point seven percent (164/408) of patients
      had GU tract anomalies, the most common being vesicoureteral reflux (VUR)
      (87/164, 53.0%). Thirty-three point two percent of the patients with acute
      pyelonephritis, confirmed by 99mTc dimercaptosuccinic acid (DMSA) renal scan, had
      VUR. CONCLUSION: Our cohort was predominated by boys, especially in those less
      than a year old. E. coli, the most common pathogen, had a higher rate of
      resistance to ampicillin and sulfamethoxazole/ trimethoprim. The pathogens that
      cause UTI were found to be becoming increasingly resistant to the common
      antimicrobial agents used in this study. The most common GU tract anomaly was
      VUR, yet the incidence was lower than that of other reports. A positive DMSA
      renal scan finding was a good indicator for prediction the possibility of VUR in
      UTI patients.

PMID- 15868849
TI  - Hyper-IgM syndrome: report of one case.
AB  - The hyper-IgM syndrome (HIM) is a rare primary immunodeficiency disorder caused
      by defects in the CD40 ligand (CD40L)/CD40-signaling pathway. It is characterized
      by recurrent infections with markedly decreased IgG, IgA and IgE levels but
      normal or elevated serum IgM levels. A 5-month-old boy presented with rapidly
      progressive pneumonia which responded poorly to antibiotics. High levels of IgM
      and very low levels of IgG, IgE and IgA were noted in his plasma specimen (IgM,
      128 mg/dl; IgG, 18 mg/dl; IgE, 1 IU/ml; IgA, 4 mg/dl). The relative proportions
      of immune cells were CD3 24.6%, CD4 10.3%, CD8 2.2%, CD19 30.2%, CD57 1.0% and
      active T cells 1.1%. After IVIG treatment, the pneumonia improved. Repeat
      assessment at the age of 15 months showed IgM decreased to the normal range (32
      mg/dl). Whole blood flow cytometry assay for CD40L expression confirmed the
      diagnosis of hyper-lgM syndrome when he was 21 months old. Only a small
      percentage (0.48%) of the patient's in vitro activated CD4+ T cells expressed
      CD40L, compared with 33.54% from a healthy control. The patient's father, mother
      and sister all had a normal CD40L expression activation patterns (43.52%, 40.78%,
      34.11%, respectively). On a regimen of monthly IVIG infusion and oral
      trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia (PCP)
      prophylaxis, the patient has had no recurrent infections.

PMID- 15868850
TI  - Imperforate hymen presenting with chronic constipation and lumbago: report of one
      case.
AB  - A history of unexplained low back pain associated with chronic constipation in an
      adolescent girl of menarchal age or in an obviously postmenarchal girl should
      make one consider an imperforate hymen with hematocolpos. This is a particular
      important differential diagnosis in the work-up of an adolescent who denies ever
      having had menses or sexual activity. The case of a girl with an imperforate
      hymen presenting with a six-month history of chronic constipation and
      intermittent low back pain is described.

PMID- 15868851
TI  - Traumatic intramural hematoma of the duodenum: report of one case.
AB  - Traumatic intramural hematoma of the duodenum is a rare entity in children. A
      high clinical index of suspicion is necessary for early and accurate diagnosis.
      We report a 10-year-old girl presenting with a sudden onset of epigastralgia
      after impact on the epigastrium by the edge of a wooden bed while playing on it.
      Symptoms of high gastrointestinal obstruction were severe, with bilious and large
      amounts of nasogastric effluent. Image studies revealed a large hematoma
      extending from the second to the third portion of the duodenum. Her condition was
      managed successfully by conservative treatments with nasogastric decompression
      and total parenteral nutrition. Her hospital course was uneventful. This report
      serves as a reminder to clinicians to consider intramural hematoma of the
      duodenum in the differential diagnosis of blunt abdominal trauma.

PMID- 15868852
TI  - Oculoauriculovertebral spectrum in an infant of diabetic mother.
AB  - This report concerns a neonatal case of oculoauriculovertebral spectrum born to a
      thirty-five years old preexisting diabetic mother. The clinical presentation
      included left atretic external auditory canal with pre-auricular skin tag,
      asymmetric hypoplastic left face, bilateral additional 13th ribs, left
      torticollis, micrognathia, and low hair line. The possible association of
      oculoauriculovertebral spectrum and maternal diabetes is discussed, and the
      literature is reviewed.

PMID- 15868853
TI  - Inflammatory pseudotumor of the bladder: a rare cause of hematuria with impending
      shock in a child.
AB  - Hematuria is one of the most common disorders in children. Bladder tumors are
      rare in children, and inflammatory pseudotumor (IP) is especially rare. We report
      a case of inflammatory pseudotumor of the bladder in a 13-year-old girl
      manifested as acute onset of non-traumatic and painless gross hematuria with
      impending hypovolemic shock. A huge intravesicular mass (6.5 x 3.8 cm) was noted
      on renal-bladder ultrasound, cystoscopy, and computed tomography. Partial
      cystectomy was performed to remove the mass. Pathology led to a diagnosis of
      leiomyoma and subsequent confirmation as an IP. To our knowledge, our case is the
      first presentation of bladder IP in Taiwan among the reported pediatric cases.

PMID- 15868854
TI  - Homing in on the home page. A look at some dynamic hospital home pages and their
      strategies for branding, informing, and marketing.

PMID- 15868855
TI  - Insurance company Web strategies evolve: A look at the trends, and three case
      examples of companies with more-advanced strategies.

PMID- 15868856
TI  - Auto-compensation of nonlinear influence of environmental parameters on the
      sensor characteristics using neural networks.
AB  - Usually the environmental parameters influence the sensor characteristics in a
      nonlinear manner. Therefore obtaining correct readout from a sensor under varying
      environmental conditions is a complex problem. In this paper we propose a neural
      network (NN)-based interface framework to automatically compensate for the
      nonlinear influence of the environmental temperature and the nonlinear-response
      characteristics of a capacitive pressure sensor (CPS) to provide correct readout.
      With extensive simulation studies we have shown that the NN-based inverse model
      of the CPS can estimate the applied pressure with a maximum error of +/- 1.0% for
      a wide temperature variation from 0 to 250 degrees C. A microcontroller unit
      based implementation scheme is also proposed.

PMID- 15868857
TI  - Characterization of a novel two-finger variable reluctance gripper.
AB  - Variable reluctance (VR) actuator has a simple and robust structure. Without any
      permanent magnet, it is low cost; easy to manufacture, highly reliable, and can
      operate in hostile temperatures. However, it is inherently nonlinear, and is
      difficult to control and operate as a proportional device. With the advancement
      of digital signal processors and power electronic drives in recent years, advance
      modeling techniques and control solutions can be realized onto VR actuators
      applications. For these reasons, VR actuators have redrawn research interests.
      The paper describes the investigation and development of a novel two-finger
      gripper using VR technology. A novel two-finger VR gripper has been proposed and
      fabricated. Characterization measurements of the VR gripper were carried out.
      Measurement results show that the proposed actuator exhibits general
      characteristics as VR actuators and becomes more efficient through making use of
      mutual coupling.

PMID- 15868858
TI  - A simplified predictive control algorithm for disturbance rejection.
AB  - Model predictive control (MPC) offers several advantages for control of chemical
      processes. However, the standard MPC may do a poor job in suppressing the effects
      of certain disturbances. This shortcoming is mainly due to the assumption that
      disturbances remain constant over the prediction horizon. In this paper, a simple
      disturbance predictor (SDP) is developed to provide predictions of the unmodeled
      deterministic disturbances for a simplified MPC algorithm. The prediction is
      developed by curve fitting of the past information. A tuning parameter is
      employed to handle a variety of disturbance dynamics and a procedure is presented
      to find an optimum value of the tuning parameter online. A comparison is made
      with the commonly used disturbance prediction on three example problems. The
      results show that an improved regulatory performance and zero offset can be
      achieved under both regular and ramp output disturbances by using the proposed
      disturbance predictor.

PMID- 15868859
TI  - Model predictive control of discrete-time hybrid systems with discrete inputs.
AB  - This paper proposes and discusses a model predictive control approach to hybrid
      systems with discrete inputs only. The algorithm, which takes into account a
      model of a hybrid system, described as a mixed logical dynamical system, is based
      on a performance-driven reachability analysis. The algorithm abstracts the
      behavior of the hybrid system by building a "tree of evolution." The nodes of the
      tree represent the reachable states of a process, and the branches connect two
      nodes if a transition exists between the corresponding states. A cost-function
      value is associated with each node, and based on this value the exploration of
      the tree is driven. As soon as the exploration of the tree is finished, the
      corresponding input is applied to the system and the procedure is repeated.

PMID- 15868860
TI  - Computation of stabilizing PI and PID controllers for processes with time delay.
AB  - In this paper, a new method for the computation of all stabilizing PI controllers
      for processes with time delay is given. The proposed method is based on plotting
      the stability boundary locus in the (kp, ki) plane and then computing the
      stabilizing values of the parameters of a PI controller for a given time delay
      system. The technique presented does not need to use Pade approximation and does
      not require sweeping over the parameters and also does not use linear programming
      to solve a set of inequalities. Thus it offers several important advantages over
      existing results obtained in this direction. Beyond stabilization, the method is
      used to compute stabilizing PI controllers which achieve user specified gain and
      phase margins. The proposed method is also used to design PID controllers for
      control systems with time delay. The limiting values of a PID controller which
      stabilize a given system with time delay are obtained in the (kp, ki) plane, (kp,
      kd) plane, and (ki, kd) plane. Examples are given to show the benefits of the
      method presented.

PMID- 15868861
TI  - Improving immunization of programmable logic controllers using weighted median
      filters.
AB  - This paper addresses the problem of improving immunization of programmable logic
      controllers (PLC's) to electromagnetic interference with impulsive
      characteristics. A filtering structure, based on weighted median filters, that
      does not require additional hardware and can be implemented in legacy PLC's is
      proposed. The filtering operation is implemented in the binary domain and removes
      the impulsive noise presented in the discrete input adding thus robustness to
      PLC's. By modifying the sampling clock structure, two variants of the filter are
      obtained. Both structures exploit the cyclic nature of the PLC to form an N
      sample observation window of the discrete input, hence a status change on it is
      determined by the filter output taking into account all the N samples avoiding
      thus that a single impulse affects the PLC functionality. A comparative study,
      based on a statistical analysis, of the different filters' performances is
      presented.

PMID- 15868862
TI  - Synthesis of nonlinear discrete control systems via time-delay affine Takagi
      Sugeno fuzzy models.
AB  - The affine Takagi-Sugeno (TS) fuzzy model played a more important role in
      nonlinear control because it can be used to approximate the nonlinear systems
      more than the homogeneous TS fuzzy models. Besides, it is known that the time
      delays exist in physical systems and the previous works did not consider the time
      delay effects in the analysis of affine TS fuzzy models. Hence a parallel
      distributed compensation based fuzzy controller design issue for discrete time
      delay affine TS fuzzy models is considered in this paper. The time-delay effect
      is considered in the discrete affine TS fuzzy models and the stabilization issue
      is developed for the nonlinear time-delay systems. Finally, a numerical
      simulation for a time-delayed nonlinear truck-trailer system is given to show the
      applications of the present approach.

PMID- 15868863
TI  - Nonlinear model-based control algorithm for a distillation column using software
      sensor.
AB  - This paper presents the design of model-based globally linearizing control (GLC)
      structure for a distillation process within the differential geometric framework.
      The model of a nonideal binary distillation column, whose characteristics were
      highly nonlinear and strongly interactive, is used as a real process. The
      classical GLC law is comprised of a transformer (input-output linearizing state
      feedback), a nonlinear state observer, and an external PI controller. The tray
      temperature based short-cut observer (TTBSCO) has been used as a state estimator
      within the control structure, in which all tray temperatures were considered to
      be measured. Accordingly, the liquid phase composition of each tray was
      calculated online using the derived temperature-composition correlation. In the
      simulation experiment, the proposed GLC coupled with TTBSCO (GLC-TTBSCO)
      outperformed a conventional PI controller based on servo performances with and
      without measurement noise as well as on regulatory behaviors. In the subsequent
      part, the GLC law has been synthesized in conjunction with tray temperature based
      reduced-order observer (GLC-TTBROO) where the distillate and bottom compositions
      of the distillation process have been inferred from top and bottom product
      temperatures respectively, which were measured online. Finally, the comparative
      performance of the GLC-TTBSCO and the GLC-TTBROO has been addressed under
      parametric uncertainty and the GLC-TTBSCO algorithm provided slightly better
      performance than the GLC-TTBROO. The resulting control laws are rather general
      and can be easily adopted for other binary distillation columns.

PMID- 15868864
TI  - Simplified modeling and generalized predictive position control of an ultrasonic
      motor.
AB  - Ultrasonic motors (USM's) possess heavy nonlinear and load dependent
      characteristics such as dead-zone and saturation reverse effects, which vary with
      driving conditions. In this paper, behavior of an ultrasonic motor is modeled
      using Hammerstein model structure and experimental measurements. Also, model
      predictive controllers are designed to obtain precise USM position control.
      Simulation results indicate improved performance of the motor for both set point
      tracking and disturbance rejection.

PMID- 15868865
TI  - Experimental evaluation of adaptive three-tank level control.
AB  - Liquid level control through regulation of mass flow rates is an important
      application in various areas of the power industry. Very often a PID controller
      is used for these applications. This paper compares a nonconventional PID
      controller and three different types of adaptive controller, a direct model
      reference adaptive controller (MRAC), an indirect MRAC with Lyapunov estimation,
      and an indirect MRAC with recursive least-squares (RLS) updating estimation, for
      liquid level control. By implementing all four controllers on a three-tank
      system, the performances of each are compared. All controllers track a sinusoidal
      input very well and overall exhibit somewhat varying performance. The direct MRAC
      and the indirect MRAC with RLS estimation give the best performance. With
      Lyapunov estimation and RLS estimation, all the system parameter estimates
      converge to the reference model values. However, RLS estimation has a much faster
      convergence. It is concluded that adaptive liquid level control is an improvement
      over traditional liquid level control when precise level control in three coupled
      tanks is desired.

PMID- 15868866
TI  - Nonintrusive frequency analysis for variable pairing on a distillation column.
AB  - This paper describes a nonintrusive plant analysis technique for variable pairing
      that relies on power spectrum frequency analysis. The development of the method
      is described and guidelines for the implementation of the method are presented.
      Information gathered from the frequency analysis is used in variable pairing to
      ensure minimal impacts from unmeasured disturbances. Specifically, the nested
      epsilon decomposition method for variable pairing is used. This nonintrusive
      analysis method is implemented on a pilot plant distillation column. The results
      of the pilot plant test are used in the decoupling of a multiloop control system.

PMID- 15868867
TI  - Online optimization of fuzzy-PID control of a thermal process.
AB  - A constrained optimization of a simple fuzzy-PID (PID-proportional integral
      derivative) system is designed for the online improvement of PID control
      performance during productive control runs. The cost function design yields a
      desirable balance between rise time, setpoint overshoot, and settling time to the
      setpoint. The constraints determined by simulation yield control performance no
      worse than the existing control performance during online optimization. The
      optimized fuzzy-PID system is compared to a similarly optimized PID controller
      and a benchmark model predictive controller.

PMID- 15868868
TI  - Multiple objective evolutionary algorithm for temporal linguistic rule
      extraction.
AB  - Autonomous temporal linguistic rule extraction is an application of growing
      interest for its relevance to both decision support systems and fuzzy
      controllers. In the presented work, rules are evaluated using three qualitative
      metrics based on their representation on the truth space diagram. Performance
      metrics are then treated as competing objectives and the multiple objective
      evolutionary algorithm is used to search for an optimal set of nondominant rules.
      Novel techniques for data pre-processing and rule set post-processing are
      designed that deal directly with the delays involved in dynamic systems. Data
      collected from a simulated hot and cold water mixer are used to validate the
      proposed procedure.

PMID- 15868869
TI  - Is GDMO a myth?

PMID- 15868870
TI  - Overweight, hypertension and ECG changes in menopausal women in West Bengal.
AB  - The prevalence of overweight with related changes in ECG and blood pressure (BP)
      were studied in thirty menopausal women from different districts of West Bengal
      to assess the effects of menopause on weight, BP and on heart in them with review
      of the literature. Both hypertension and ischaemia were increased to 77% and 43%
      in the study group compared to control group values of 50% and 30% respectively.
      All the 3 persons in the control group showing ischaemic change were hypertensive
      while among 13 persons in the study group who showed ischaemia; 3 had normal BP
      and 10 were hypertensive. In the menopausal (study) group, 30% showed
      irregularities of heart rate compared to 10% women in the premenopausal (control)
      group. The dramatic effect of exercise in reducing the ECG changes seen in the
      control group were not seen in the study group.

PMID- 15868871
TI  - Prepubertal testicular tumours in Kashmir--a histopathological report of 15
      cases.
AB  - A total of 15 cases of prepubertal testicular tumours were reported by the
      department of pathology, Government Medical College, Srinagar, Kashmir over a
      period of 15 years, from January 1984 to December 1998. The cases included yolk
      sac tumour (10 cases; 67%), teratoma [(mature) 2 cases (13%)], rhabdomyosarcoma
      [(paratesticular) 2 cases (13%)] and NHL-Burkitt's lymphoma [one case (7%)]. The
      youngest patient was 10 months old and the oldest was of 14 years age. Ten cases
      (67%) occurred at or below the age of 4 years. The youngest patient had yolk sac
      tumour and oldest had rhabdomyosarcoma. In 2 cases both the testes were involved
      with one of these two cases having bilateral undescended testes.

PMID- 15868872
TI  - Management of different types of wound by cyanoacrylate glue fixation: a random
      study of 213 patients.
AB  - A random study for management of wound by cyanoacrylate glue in 213 patients,
      irrespective of age and sex with different types of wounds was carried out over a
      period of 4 years (1996-2000). In this series both dean surgical wounds and
      infected accidental wounds were included. Most of the patients recovered
      uneventfully, except 5, who showed wound gap. Reapplication of glue was done on
      them and 3 had similar wound union but 2 patients (0.94%) required surgical
      suture.

PMID- 15868873
TI  - Status report on DOTS expansion and implementation during the 2nd quarter 2004
      (April-June 2004).
AB  - DGHS, MoHFW gives a status report on DOTS expansion and implementation during the
      2nd quarter 2004 inviting co-operation from all sectors to reach the target of
      covering the entire country under DOTS by 2005.

PMID- 15868874
TI  - Factors influencing refusal by relatives of brain-dead patients to give consent
      for organ donation: experience at a transplant centre.
AB  - To analyse the reasons for family refusal for donating the organs of their
      deceased relatives, 33 families were approached and interviewed as a part of the
      consent process. Thirty of these refused and their reasons for refusal were
      documented. In 83%, the principle reason for refusal to give consent was the non
      acceptance of brain death. Superstitions relating to being reborn with a missing
      organ (that had been donated) in 40% or that tampering with the body would not
      free their dead relatives from the cycle of life-death-rebirth in 26% were next
      most frequently voiced. A delay in funeral (23%), lack of consensus within family
      members (17%), fear of social criticism (10%), dissatisfaction with the hospital
      staff (10%) and being unaware of their deceased relatives' wishes (6%) were the
      other reasons cited.

PMID- 15868876
TI  - Isolated omental hydatid cyst--a case report.
AB  - Isolated omental hydatid cyst is a very rare clinical entity. Here, such a case
      has been presented where abdominal cystic mass came out as isolated hydatid cyst
      in the greater omentum.

PMID- 15868875
TI  - Central nervous system fungal infection--a report of three cases.
AB  - Fungal infections of the central nervous system in three apparently
      immunocompetent patients are being reported. Two cases of cerebral aspergillosis
      presenting as intracranial granulomas such as rhinocerebral and intracranial
      forms, and one of cryptococcal meningitis could be successfully diagnosed by
      newer diagnostic modality such as antigen detection techniques. The case with
      cryptococcal infection had typical neuroimaging feature which helped to suspect
      the underlying diagnosis. Aspergillus galactomannan detection in the
      cerebrospinal fluid helped in the early diagnosis and appropriate therapy of one
      patient.

PMID- 15868877
TI  - Kocher Debre Semelaigne syndrome--a case report and review of literature.
AB  - A case of muscular hypertrophy in a hypothyroid 12-year-old male child, known as
      Kocher Debre Semelaigne syndrome, is reported with review of the relevant
      literature. The patient responded well to l-thyroxine therapy.

PMID- 15868878
TI  - A case of opsoclonus-myoclonus-ataxia with neuroblastoma.
AB  - A 2 year old boy presented with features of opsoclonus, myoclonus and ataxia.
      Routine investigations of blood, urine, x-ray chest, bone scan, EEG and MRI of
      brain, were normal. Urine for VMA was negative. A right suprarenal mass was
      detected at MRI of abdomen. The mass was resected completely and was found
      histologically to be of differentiating type of neuroblastoma. The child was
      treated initially with prednisolone for 6 weeks along with sodium valproate. He
      is still on sodium valproate for his neurological symptoms. His symptoms still
      persist though they have decreased in intensity.

PMID- 15868879
TI  - Pseudomyxoma peritonei presenting as sub-acute large bowel obstruction.
AB  - A case of pseudomyxoma peritonei, a rare mucin-secreting tumour in the
      peritoneum, in a 30-year-old male and presenting as sub-acute large bowel
      obstruction, is reported here with review of the literature.

PMID- 15868880
TI  - Rethinking public relation strategies of hospitals.

PMID- 15868881
TI  - Interstitial lung disease and vasculitis in a case of rheumatoid arthritis.

PMID- 15868882
TI  - Making Revised National Tuberculosis Control Programme (RNTCP) more child
      friendly.

PMID- 15868883
TI  - Diarrhoea developing in hospital patients.

PMID- 15868884
TI  - Comparison of diets high in monounsaturated versus polyunsaturated fatty acid on
      postprandial lipoproteins in diabetes.
AB  - BACKGROUND: Postprandial hypertriglyceridaemia is common in diabetes. Fatty acids
      are regulators of gene expression and may play an important role in regulatingthe
      postprandial lipoprotein cascade. AIM: To examine postprandial lipoprotein
      differences between diabetic and control subjects on polyunsaturated (linoleic)
      and monounsaturated (oleic) fat diets. METHODS: A randomised, crossover study.
      RESULTS: LDL was greater and HDL less (p < 0.05) in diabetic patients compared to
      controls on the linoleic acid diet. Apo E per particle was significantly lower in
      the diabetic patients compared to control subjects on both linoleic (p < 0.05)
      and oleic acid diets (p < 0.01). HDL apo E was also significantly lower in the
      diabetic patients compared to controls on the linoleic acid diet (p < 0.02).
      CONCLUSION: A change from linoleic to oleic acid diet resulted in an improvement
      in LDL and HDL in the diabetic patients. We suggest that the reduced apo
      E/particle in the diabetic patients may be an explanation for the delayed
      lipoprotein clearance.

PMID- 15868885
TI  - The importance of microbiological investigations, medications and artificial
      feeding in diarrhoea evaluation.
AB  - BACKGROUND: Diarrhoea in hospitalised patients is usually attributed to
      medications especially antibiotics, enteral tube feeding or enteropathogenic
      bacteria particularly Clostridium difficile. AIMS: The aim of this study was to
      evaluate the investigations performed on patients who developed diarrhoea during
      their stay in an acute general hospital. METHOD: Over 18 working days, an
      unselected group of adult inpatients who developed diarrhoea following their
      admission to hospital were reviewed. Symptoms, medications, nutritional support
      and any investigations performed were assessed. RESULTS: Eighty-one patients
      developed diarrhoea. Forty-nine (60%) were receiving antibiotics prior to the
      development of symptoms, 30 (37%) were being enterally tube fed, 14 (17%) had
      positive stool for Clostridium difficile A and B toxin and 3 (4%) had salmonella
      species positive stool. CONCLUSION: The majority of cases of diarrhoea were
      related to medications and enteral tube feeding. A small but significant number
      did develop bacterial infections. In contrast to some suggested guidelines, when
      investigating hospital acquired diarrhoea, it is considered worthwhile to perform
      microbiological stool examinations.

PMID- 15868886
TI  - Perceived efficacy and risks of infection following intra-articular injections: a
      survey of orthopaedic surgeons.
AB  - BACKGROUND: Efficacy of intra-articular injections is controversial and published
      studies on efficacy and risks are few. AIMS: We sought the opinion of practicing
      orthopaedic consultants in order to establish the perceived benefits and risks of
      infection following intra-articular steroids. METHODS: A questionnaire was sent
      to all the orthopaedic consultants in the UK and Ireland on the use of intra
      articular steroids. RESULTS: A total of 853 completed questionnaires (response
      rate 57.4%) were analysed. The perceived risk of infection was 1:1000 in almost
      half of the surgeons polled and 1:10,000 in one third. The 759 consultants who
      administer intra-articular steroids recalled sixty-eight cases of infection; 85.2
      % of the surgeons rated efficacy 5 or above on a visual analog score of 1-10.
      CONCLUSIONS: Correct patient selection, proper indications for use, and a limited
      number of appropriately spaced injections were all perceived to be important to
      achieve maximum benefit without serious side-effects.

PMID- 15868887
TI  - Solitary plasmacytoma: experiences from Central Anatolia.
AB  - BACKGROUND: Solitary plasmacytoma localised to bone or soft tissue without
      myeloma. AIM: Clinical features and survival was analysed in patients from
      Central Anatolia. METHODS: Twenty-three solitary plasmacytoma (18 male, 5 female)
      were evaluated retrospectively. Median age was 58 years (46-72). The major
      localisation was vertebral column. RESULTS: All patients but one (larynx) had
      surgical resection and 21 patients received radiotherapy postoperatively.
      Multiple myeloma developed in eight patients (35%) and local relapse was detected
      in one patient. Eight patients died, causes of death were multiple myeloma
      progression in six patients, local relapse of intracranial plasmacytoma in one
      patient and cranial trauma in one patient who was in complete remission. Three
      and 5 years progression free survival were 45.6% and 22.8% respectively and
      overall survivals were 54.4% and 27.2% respectively. CONCLUSION: Solitary
      plasmacytoma cases should be followed carefully regarding local relapse and
      progression to myeloma.

PMID- 15868889
TI  - Outcomes of adult cadaveric renal transplantation in ireland 1986 to 2001.
AB  - BACKGROUND: Since the introduction of renal transplantation in the Republic of
      Ireland in 1964, the number of transplants performed annually has increased from
      single figures in the 1960s to the current rate of approximately 130 renal
      transplants per year. Improvements in graft and patient outcomes have been
      associated with the introduction of the immunosuppressive agent Cyclosporin (CSA)
      in the mid 1980s. AIMS: The aim of this study was to examine trends in outcomes
      and factors that influence outcomes for adult kidney transplantation from 1986 to
      2001. METHODS: All adult cadaveric kidney transplantations carried out between
      1986 and 2001 were included. We separated the transplanted grafts and patients
      into four time periods; 1986-1989, 1990-1993, 1994-1997, 1998-2001. Graft and
      patient survival outcomes were compared for the different periods. RESULTS: The
      one-year kidney graft survival rate increased from 82% during 1986-1989 to 86%
      during 1998-2001. Patient survival over the four time periods studied has
      remained stable at approximately 95% at one year. CONCLUSION: We report a
      significant improvement in kidney graft outcomes over the past 16 years. Patient
      survival has remained relatively stable during this period.

PMID- 15868888
TI  - Hepatitis C viral clearance in an intravenous drug-using cohort in the Dublin
      area.
AB  - BACKGROUND: The rate of spontaneous HCV viral clearance is reported as 20-25% but
      recent data indicate a higher frequency in some cohorts. The rate of spontaneous
      clearance in intravenous drug users has not been reported in an Irish setting.
      AIMS: To determine the rate of spontaneous hepatitis C viral clearance and
      genotype in an Irish intravenous drug-using cohort. METHODS: Drug users attending
      five drug treatment clinics in the Dublin were investigated. Data were
      prospectively recorded from January 1997 to June 2001 and follow-up testing
      completed in 2003. There were 496 HCV antibody positive patients identified and
      assessed for HCV RNA clearance. All were HIV and hepatitis B negative, 68.8% were
      male. RESULTS: HCV RNA negativity (viral clearance) was documented in 38% of
      patients. Viral clearance was 47.4% in females and 34.5% in males (p = 000.6).
      Clearance was independent of age or duration of intravenous drug use. Viral
      clearance as defined as two negative consecutive HCV RNA tests, a minimum of one
      year apart, was sustained in 82.2% at two-year follow-up, giving an overall viral
      clearance of 31.1%. HCV genotype 1 and 3 were most commonly identified at 48.8%
      and 48.5% respectively in those with chronic infection. CONCLUSIONS: Spontaneous
      HCV viral clearance occurs at a higher frequency than previously reported.
      Genotype 1 and 3 are commonest in the patient cohort.

PMID- 15868890
TI  - Compliance of external hip protector use amongst elderly day hospital attenders.
AB  - BACKGROUND: When worn external Hip Protectors (EHP) reduce hip fracture but poor
      compliance results in reduced efficacy. AIMS: We determined the compliance with
      EHP therapy among a group of elderly people attending a day hospital. METHODS:
      Forty-five patients or their care-givers were interviewed a mean (sd) 334 (150)
      days after they had been given EHP. RESULTS: There were 12 men and 33 women with
      mean age of 80 (7) years. Only ten (22%) were still wearing EHP properly. Those
      who were compliant were given their EHP more recently than those who were not
      (277 (118) days vs 403 (159), p = 0.0062) and were more likely to feel safer when
      wearing them (p = 00.017, chi2= 5.68). Reasons for non-compliance included
      exclusive outdoor wear, discomfort and inconvenience. CONCLUSIONS: Hip protector
      compliance was poor in this small study of elderly individuals attending a day
      hospital. Better patient education may improve compliance though this needs to be
      determined.

PMID- 15868891
TI  - Fractured penis: a clinical misnomer!
AB  - BACKGROUND: A 'fracture' of the penis refers to a tear in the deep layer of the
      tunica albuginea (Buck's fascia) and may be associated with a urethral injury.
      AIM: To describe a classical case of a 'fractured' penis and discuss the
      management options. METHOD: A case report of a 30-year-old man presented with a
      'fractured' penis and who underwent surgical intervention. CONCLUSION: This rare
      occurrence represents a urological emergency and necessitates imaging and repair
      of the cavernosal defect in order to prevent poor functional outcome.

PMID- 15868892
TI  - Advanced Merkel cell cancer and the elderly.
AB  - BACKGROUND: Merkel cell cancer (MCC) is an uncommon neuroendocrine skin cancer
      occurring predominantly in elderly Caucasians. It tends to metastasize to
      regional lymph nodes and viscera and is sensitive to chemotherapy but recurs
      rapidly. AIM: To report one such case, its response to chemotherapy and briefly
      review the literature. METHODS: A 73-year-old male with a fungating primary
      lesion on his left knee and ulcerated inguinal lymph nodes was diagnosed with MCC
      and treated with chemotherapy. The two largest case series and reviews of case
      reports were summarised. RESULTS: His ulcer healed after two cycles of
      carboplatin and etoposide with improvement in quality of life. Overall response
      rates of nearly 60% to chemotherapy are reported but median survival is only nine
      months with metastatic disease. CONCLUSIONS: Chemotherapy should be considered
      for fit elderly patients with MCC who have recurrent or advanced disease.

PMID- 15868893
TI  - Cannonball metastases with favourable prognosis.
AB  - BACKGROUND: Secondary 'cannonball' metastases to the lung are frequent and
      usually associated with disseminated malignancy and poor prognosis. AIM: To
      report the case of a patient with metastatic pulmonary endometrial stromal
      sarcoma who had a previous hysterectomy for benign uterine fibroids and no past
      history of malignancy. RESULT: A 70-year-old female presented with cannonball
      metastases in her lung. Four years previously she had a hysterectomy for
      'fibroids'. Review of the original histology revealed endometrial stromal
      sarcoma, similar to the lung metastasis. She currently has a good prognosis.
      CONCLUSION: A patient with 'cannonball' metastases can have a favourable
      prognosis. A female patient with a previous hysterectomy for uterine fibroids,
      should be considered to have metastatic sarcoma until proven otherwise.

PMID- 15868894
TI  - An unusual case of appendicitis.
AB  - BACKGROUND: Acute appendicitis in elderly patients often presents late and
      atypically. Presentation as an incarcerated femoral hernia is rare. AIM: To
      describe the management of an elderly patient presenting with acute appendicitis
      in an incarcerated femoral hernia. METHODS: The femoral canal was explored and
      the hernia repaired. Formal appendicectomy was performed via a midline laparotomy
      incision. RESULTS: Histological examination confirmed the diagnosis of acute
      appendicitis. CONCLUSION: Unusual clinical presentations of acute appendicitis
      represent an interesting diagnostic challenge.

PMID- 15868895
TI  - Ureteral endometriosis and ovarian mucinous cystadenoma presenting with acute
      pyonephrosis.
AB  - BACKGROUND: Endometriosis is a common disease, but ureteral involvement is rare.
      Nonspecific clinical presentations of ureteral endometriosis may result in
      diagnostic difficulty. AIM: To discuss the diagnosis and management of such a
      case. METHODS: To report a case of ureteral involvement with endometriosis and
      review the literature. RESULTS: The case presented with right lower quadrant pain
      giving rise to initial diagnostic possibility of acute appendicitis. Subsequent
      evaluation revealed the diagnosis of right pyonephrosis due to midureteral
      endometriosis with right ovarian mucinous cystadenoma. CONCLUSION: The diagnosis
      of ureteral endometriosis requires a high index of clinical suspicion. The
      importance of ultrasound in the evaluation of acute abdomen in women can not be
      overemphasised.

PMID- 15868896
TI  - George Eliot and the doctors.

PMID- 15868897
TI  - Immunophenotypic and molecular cytogenetic features of the cell line UP-LN1
      established from a lymph node metastasis of a poorly-differentiated carcinoma.
AB  - A lymph node metastatic cell line (UP-LN1) was established in vitro from a poorly
      differentiated epithelial tumor, and characterized for immunobiological and
      molecular cytogenetic profiles. The morphology of UP-LN1 cells when grown as
      monolayers was unique in that, apart from typical colonies of adherent epithelial
      cells, many loosely attached round cell colonies emerged on and around the
      patches of epithelial cells. By means of immunofluorescence/flow cytometric
      analysis, UP-LN1 cells showed selective expression of cytokeratin markers AE1 and
      CK20, but expressed AE3 and CK7 poorly. The expression of CEA and CK20 but not
      CK7 in UP-LN1 cells was also exhibited in the tumor biopsy by
      immunohistochemistry, suggesting a gastrointestinal origin of this tumor. Down
      regulation of HLA-class I and other surface molecules including ICAM-1, CD44s,
      CD44v5, CD44v6 and E-cadherin were observed, which all pointed to a
      progressive/invasive phenotype of the tumor. Spectral karyotyping revealed a
      hypertriploid (approximately 3n) chromosome content with 73-76 chromosomes,
      including numerical alterations and translocated derivative chromosomes. Seven
      different translocation chromosomes were observed, four of which involved
      chromosome 19. Numerical imbalances were also assessed by comparative genomic
      hybridization. This cell line should be useful for further studies of tumor
      invasion and metastatic processes because of the unusual in vitro and in vivo
      immunobiological and genetic characteristics observed.

PMID- 15868898
TI  - The role of macrophages in angiogenesis. Comparison between HIV+ and HIV-
      populations with anal dysplasia and anal cancer.
AB  - BACKGROUND: While macrophages (CD68+) have been associated with angiogenesis in
      some inflammatory and neoplastic processes by increasing the release of vascular
      endothelial growth factor (VEGF), their role in anal intraepithelial neoplasia
      (AIN) and anal squamous cell carcinoma has not been established. This study
      records macrophage infiltration in anal pre-invasive and invasive lesions in HIV+
      and HIV- populations, and determines their relationship with angiogenesis.
      MATERIALS AND METHODS: Sixty patients (31 HIV+) with AIN and anal SCC were
      studied. Paraffin sections were stained for CD68, VEGF and von Willebrand factor.
      The density of CD68 cells, the expression of VEGF and angiogenesis were
      quantified, and compared amongst groups and between HIV+ and HIV- populations.
      RESULTS: All three parameters increased linearly as the lesions became more
      dysplastic, in HIV+ and HIV- groups. The CD68 count was statistically lower in
      HIV+ (p<0.005) compared with HIV- groups, while the differences in VEGF
      expression and in angiogenesis were not significant between HIV+ and HIV-
      populations. CONCLUSION: There was a significant decrease of macrophage
      infiltrate in the HIV+ group. The relative increase in VEGF expression and
      angiogenesis in the face of lower macrophage infiltration in HIV+ patients may be
      explained either by a greater release of angiogenic factors by macrophages, or by
      VEGF expression not being solely dependent on macrophage activation.

PMID- 15868899
TI  - A potential role for vascular endothelial growth factor-D as an autocrine growth
      factor for human breast carcinoma cells.
AB  - BACKGROUND: Vascular endothelial growth factor-D (VEGF-D) binds and activates
      vascular endothelial growth factor receptor-2 (VEGFR-2), which signals for
      angiogenesis, and VEGFR-3, which signals for lymphangiogenesis. Besides
      endothelial cells, VEGFR-2 has been detected on malignant cells, including human
      breast carcinoma cells. MATERIALS AND METHODS: It was examined if ectopic
      expression of human VEGF-D affected growth of breast carcinoma cell lines in
      vitro and in vivo. RESULTS: VEGF-D overexpressing clonal MCF-7 and MDA-MB-231
      cell lines displayed increased proliferative activities and upregulation of
      cyclins A, D1 and D3, compared to the vector control. Following subcutaneous
      inoculation of the MDA-MB-231 cells into nude mice, growth of the VEGF-D
      overexpressing cells was greatly accelerated. The tumor weight gain was
      accompanied by increased proliferative activity, cyclin A expression and
      microvascular density. CONCLUSIONS: These findings suggest that VEGF-D functions
      both as an autocrine growth factor and a stimulator of angiogenesis in breast
      cancer.

PMID- 15868900
TI  - Involvement of proinflammatory cytokines IL-1beta and IL-6 in progression of
      human gastric carcinoma.
AB  - Gastric carcinoma occurs in response to chronic inflammation of gastric mucosa
      infected with Helicobacter pylori. It is not known how cytokines affect the
      growth and progression of gastric carcinoma. MATERIALS AND METHODS: We measured
      tissue concentrations of the proinflammatory cytokines interleukin (IL)-1beta and
      IL-6 in gastric carcinoma and investigated the correlation between the levels of
      these cytokines and clinicopathological features. Biopsy specimens of tumors or
      adjacent normal mucosa were obtained from 42 Japanese patients with gastric
      carcinoma. Tissue levels of IL-1beta and IL-6 were measured by enzyme-linked
      immunosorbent assay. RESULTS: IL-1beta levels were significantly higher in the
      neoplasm than in the corresponding normal mucosa. The IL-6 levels in the neoplasm
      correlated significantly with the depth of invasion and lymphatic invasion. High
      levels of IL-1beta and IL-6 were characteristic of non-scirrhous type gastric
      carcinoma. CONCLUSION: These results suggest that IL-1beta and IL-6 are involved
      in the growth and progression of human gastric carcinoma.

PMID- 15868901
TI  - Stimulation of human T cells by an influenza A vector expressing a CTL epitope
      from the HER-2/neu protooncogene results in higher numbers of antigen-specific
      TCRhi cells than stimulation with peptide. Divergent roles of IL-2 and IL-15.
AB  - Development of cancer vaccines requires approaches to induce expansion and
      functional differentiation of tumor antigen-specific effector and memory cells.
      The later are particularly relevant for prevention of disease relapse. Efficient
      induction of memory cells is hindered by the lack of information about the
      relationship between TCR stimulation and the cytokines required for Ag-specific
      memory CD8+ cells and proliferation and survival. Since viruses are known to
      induce memory T cells, an attenuated influenza A/PR8/34 virus with a truncated
      nonstructural (NS1) gene was generated containing the HER-2 CTL E75 epitope in
      its neuraminidase protein (KIF-NS virus). Stimulation of PBMC from healthy donors
      and of tumor-associated lymphocytes (TAL) from ovarian cancer patients with
      dendritic cells (DC) infected with KIF-NS (KIF-NS-DC), induced higher numbers of
      immediate memory effector CD8+ CD44hi CD122hi cells, expressing TCR specific for
      E75 (E75-TCR) than stimulation with peptide E75. Survival of CD44hi CD122hi cells
      was dependent on the levels of TCR; cells expressing lower levels of E75-TCR
      (MFI: 10(2)-10(3)) survived better in IL-2 while cells expressing high levels of
      TCR (MFI: 10(3)-10(4)) survived better in IL-15. This is the first report
      demonstrating induction of human Ag-specific memory CD8+ cells against a human
      tumor-antigen using a live attenuated recombinant influenza virus vector. Such
      vectors may provide a novel approach for preventive immunity in human cancer
      vaccine development.

PMID- 15868902
TI  - Carboxyamido-triazole (CAI) reverses the balance between proliferation and
      apoptosis in a rat bladder cancer model.
AB  - Carboxyamido-triazole (CAI) is an orally bioavailable calcium influx and signal
      transduction inhibitor that has been shown to be anti-invasive, anti-angiogenic
      and anti-metastatic in different human tumors including transitional cell
      carcinoma. This study was undertaken to further evaluate the activity of CAI in a
      rat bladder cancer model. A transitional cell carcinoma (TCC) was chemically
      induced by intravesical installation of methyl-nitrosurea (MNU) in the bladder of
      female Fischer 344 rats. First, a toxicity study was performed which revealed no
      side-effects of CAI in the animals up to a dose of 250 mg/kg CAI. For treatment,
      a dose of 100 mg/kg CAI dissolved in PEG-400 vehicle was chosen. Oral
      administration of CAI continuously daily for 4 weeks (group A), 3 days/week over
      6 weeks (group B), or intravesically twice a week for 6 weeks (group C) caused a
      reduction of spontaneous development of TCC. Lower stage and grade of tumors were
      seen in all CAI-treated animals. Under CAI treatment, the apoptotic rate in
      tumors increased, whereas the proliferation rate decreased, as shown by TUNEL
      assay and KI-67-immunhistochemistry, respectively. The highest efficacy was seen
      in group B, with 5 out of 10 animals tumor-free. Intravesical application (group
      C) resulted in 3 out of 10 animals tumor-free. Normal urothelium was not affected
      by CAI. This animal model confirms the anti-tumor effect of CAI and shows
      induction of apoptosis and growth inhibition in bladder cancer by the drug.

PMID- 15868903
TI  - WNT5A expression in human breast cancer.
AB  - The Wnt family encodes secreted signaling molecules involved in cell adhesion
      and, by implication, cell growth. Wnt5a has been shown to behave as a putative
      oncogene and also as a tumour suppressor gene. This is a reflection of its role
      within a multi-step pathway and in the variety of ways in which its production
      can be stimulated or switched off. Wnt genes can be functionally separated into
      two classes; those that activate the canonical Wnt/beta-catenin pathway and those
      that activate the Wnt/Ca++ pathway. Wnt5a signals through frizzled receptors and,
      depending upon which frizzled receptor is present, may activate either pathway.
      Therefore the observed function of Wnt5a is entirely dependent upon its context,
      hence the confusion over its role in tumorigenesis. This study examines Wnt5a
      mRNA expression using RT-PCR in human breast cancer. MATERIALS AND METHODS: One
      hundred and twenty malignant breast tumours and 33 normal breast tissues were
      analysed. The levels of transcription of Wnt5a were determined using real-time
      quantitative PCR. Levels of expression were analysed against staging, nodal
      involvement, grade, distant metastasis and survival over a 6-year follow-up
      period. RESULTS: Levels of Wnt5a mRNA were lower in tumours than in normal tissue
      (mean values: 107 vs. 62.7). They fell further with increasing stage using the
      Nottingham Prognostic Index. This became statistically significant when NPI3 was
      compared to normal tissue (p=0.043, t-test). There was a trend towards lower
      levels of Wnt5a in those with progressive disease, however, this did not reach
      statistical significance. In patients with ER-negative disease, lower levels of
      Wnt5a were significantly associated with a worse clinical outcome (p=0.016).
      CONCLUSION: There is a trend for mRNA levels to be lower in cancerous tissue and
      lower still in those showing more aggressive behaviour. This is consistent with
      the hypothesis that Wnt5a is a tumour suppressor gene with potential clinical
      applications.

PMID- 15868904
TI  - Paclitaxel inhibits natural killer cell binding to target cells by down
      regulating adhesion molecule expression.
AB  - BACKGROUND: Chemotherapy with paclitaxel is associated with impaired natural
      killer (NK) cell function. The purpose of this study was to determine the effect
      of paclitaxel treatment on NK cell adherence to target cells. MATERIALS AND
      METHODS: Human NK-like YT cells or NK-sensitive K562 cells were exposed to
      submaximal cytotoxic concentrations (EC10 and EC30) of paclitaxel. The ability of
      surviving YT or K562 cells to adhere to untreated K562 cells or YT cells,
      respectively, was assessed in a conjugation assay. The effect of paclitaxel on
      adhesion molecule expression was determined by flow cytometry. RESULTS:
      Paclitaxel treatment resulted in decreased conjugate formation, as well as
      decreased alpha4, alphaL, and beta7 integrin expression by YT cells and decreased
      ICAM-1 expression by K562 cells. CONCLUSIONS: Paclitaxel inhibition of adhesion
      molecule expression resulted in impaired NK cell binding to target cells, which
      may have a negative impact on immune surveillance.

PMID- 15868905
TI  - Effect of low-dose tumor necrosis factor-alpha in combination with STEALTH
      liposomal cisplatin (SPI-077) on soft-tissue- and osteosarcoma-bearing rats.
AB  - Cisplatin is a widely used agent for treatment of solid tumors, but its clinical
      utility is limited by toxicity. Preclinical studies have shown less acute
      toxicity when STEALTH liposomal cisplatin (SPI-077) is used, with antitumor
      effects equivalent to those of intravenously administered free cisplatin. We
      previously reported that systemic treatment with low-dose tumor necrosis factor
      alpha (TNF) augments the activity of STEALTH liposomal doxorubicin (Doxil). In
      this study, we examined the effect of repeated systemic applications of low-dose
      TNF on the antitumor activity of SPI-077 in rats with soft-tissue sarcoma or
      osteosarcoma. Addition of TNF to SPI-077 treatment showed an improved tumor
      growth delay of the soft-tissue sarcoma. The combined SPI-077/TNF treatment
      resulted in a more prolonged antitumor activity, whereas free cisplatin showed a
      better tumor response, however with a rapid outgrowth a few days after the end of
      therapy. In the osteosarcoma, free cisplatin did not have an antitumor effect,
      but addition of TNF caused a clear tumor growth delay. SPI-077 alone resulted in
      a tumor growth delay, but combination with TNF had no additive effect. SPI-077
      yielded less systemic toxicity than cisplatin. Depending on the type of tumor,
      the addition of TNF to SPI-077 results in a better tumor growth delay with a
      prolonged antitumor effect and, in combination with the reduced toxicity of SPI
      077, this combination may be preferable to cisplatin.

PMID- 15868906
TI  - The expression of integrin alpha(v)beta6 promotes the epithelial cell morphology
      and suppresses invasive behavior in transformed oral keratinocytes.
AB  - The expression of the integrin alpha(v)beta6 has been correlated with oral SCC
      invasion. We evaluated its expression in three 4NQO transformed murine oral
      keratinocyte cell lines (B7E3, B7E11 and B4B8). The B7E3 cells were negative for
      beta6, whereas the B7E11 and the B4B8 cells were both positive. The beta6
      negative B7E3 cells were fibroblast-like in appearance, whereas the B7E11 cells
      were more epithelial-like. The B4B8 cells were a mixture of the two cell types.
      Using immunofluorescent microscopy, we found that vimentin was highly expressed
      in the B7E3 cells, whereas the B7E11 cells keratin positive. The B4B8 cells
      expressed both filaments. The B7E3 cells formed large tumors when injected into
      nude mice, whereas the B4B8 cells formed small tumors and the B7E11 cells formed
      none. These results suggest that the expression of the alpha(v)beta6 integrin
      suppresses tumor formation and may promote the epithelial phenotype in 4NQO
      transformed murine oral keratinocytes.

PMID- 15868907
TI  - Thrombospondin-1 (TSP-1) and TSP-1-derived heparin-binding peptides induce
      promyelocytic leukemia cell differentiation and apoptosis.
AB  - Thrombospondin-1 (TSP-1) is a multifunctional adhesive glycoprotein that is
      synthesized by several cell types and modulates cell growth and differentiation.
      In this study, we showed that the amount of TSP-1 secreted by two human leukemia
      cell lines, HL-60 and NB4, increased markedly during differentiation of these
      cells by all-trans retinoic acid (ATRA) (10(-7) M), reaching about 100 ng/10(6)
      cells after 3 days. Addition of purified TSP-1 alone (10(-9)-5 x 10(-8) M) to HL
      60 or NB4 cell cultures dose-dependently inhibited cell growth and
      differentiation. Differently to ATRA, TSP-1-induced differentiation of HL-60 and
      NB4 cells occurred independently of Bcl-2 regulation, as shown by
      immunofluorescence and Western immunoblotting. At day 5, TSP-1 also induced
      promyelocytic leukemia cell apoptosis. The percentage of apoptotic cells in NB4
      cultures was higher with TSP-1 (5 x 10(-8) M) than with ATRA (10(-7) M) (46+/-3%
      versus 19+/-7%, p<0.001), whereas similar levels of apoptosis (37+/-7% and 38+/
      6%) were reached with both agents in HL-60 cultures. Studies performed with
      synthetic peptides derived from the TSP-1 sequence indicated that two heparin
      binding peptides, Hep-I and GGWSHW, located within the NH2-terminal and type 1
      repeats respectively, were strong inducers of apoptosis of HL-60 and NB4 cells,
      suggesting that cell surface heparan sulfate molecules might be involved in the
      apoptotic effect of TSP-1 on promyelocytic cells.

PMID- 15868908
TI  - Activity and therapeutic potential of ORI-1001 antisense oligonucleotide on human
      papillomavirus replication utilizing a model of dysplastic human epithelium.
AB  - Human Papillomaviruses (HPVs) are small double-stranded DNA viruses that infect
      the cutaneous or mucosal epithelium. The high-risk genital HPVs are associated
      with squamous intraepithelial lesions of the anogenital region that can progress
      to cancer. Cervical cancer is the third leading cause of cancer death in women
      worldwide, yet there are no specific therapeutic treatments for HPV-associated
      malignancies. Development of specific antisense oligonucleotides as antiviral
      agents is an alternative therapeutic strategy. We utilized the organotypic raft
      culture system which recapitulates the entire HPV life cycle, including the
      production of infectious virions. We studied the effect of the ORI-1001 antisense
      phosphorothioate oligonucleotide designed against the E1 mRNA translation start
      site of low-risk HPV6 and HPV11, and tested it against high-risk HPV31b and HPV16
      vegetative replication and oncogene promoter activity. ORI-1001 significantly
      inhibited HPV31b genome amplification. In contrast, HPV16 genome amplification
      was unaffected. In addition, ORI-1001 significantly downregulated transcriptional
      activity from a HPV31b p99 early promoter luciferase reporter construct, and
      inhibited E1 and E6E7 transcript expression from the wild-type genome. Our
      results support the idea that the antisense activity of OR-1001 can target HPV31b
      functional activities in the differentiation dependent life cycle of this virus.
      Our results predict that binding stability between antisense oligonucleotides
      with partial homology to HPV genes may mediate targeting of multiple HPV types.
      Our studies also highlight the utility of the raft culture system in defining the
      parameters for testing antisense oligonucleotides against HPV.

PMID- 15868909
TI  - Apoptotic anticancer effect of alvaradoin E isolated from Alvaradoa haitiensis.
AB  - Two anthracenone C-glycosides, alvaradoins E and F, isolated from the leaves of
      Alvaradoa haitiensis Urb. (Simaroubaceae), were found to have potent inhibitory
      activities with cultured cancer cells. Using the in vivo hollow fiber model,
      these compounds demonstrated significant growth inhibition at the i.p. site when
      tested with KB, LNCaP, and Col2 cells. To determine if these anthracenone C
      glycosides mediated anticancer activity through an apoptotic pathway, a series of
      assays were performed with the 10S isomeric compound, alvaradoin E. With a DAPI
      assay, treatment of LNCaP cells with alvaradoin E at concentrations of 0.4, 2,
      10, or 50 microM for 24 or 48 h showed chromatin condensation, a morphological
      characteristic of apoptosis. Mitochondrial membrane potential, analyzed with a
      DiOC6 uptake assay, showed that treatment of LNCaP cells with 0.07, 0.14, 0.28,
      0.56, 0.86, and 1.12 microM alvaradoin E for 12 h caused dose-dependent membrane
      depolarization, another indication of early apoptosis. Also, with an annexin V
      FITC assay system, treatment of HL-60 cells with 0.07 microM alvaradoin E for 24
      h increased annexin V-FITC binding from 3 to 25.9% (8.6-fold). Finally, with the
      TUNEL assay system, treatment of HL-60 cells with 1.12 microM alvaradoin E for 32
      h increased FITC-dUTP binding from 1.2 to 12.1% (10-fold). These data suggest
      alvaradoin E is an effective anticancer agent that induces apoptosis. Additional
      studies to establish clinical utility should be of interest.

PMID- 15868910
TI  - Inhibition of mTOR suppresses experimental liver tumours.
AB  - Sirolimus, and its antiproliferative capacity, was studied in vivo in three
      different syngenic rat tumours in the liver. Sirolimus is an inhibitor of the
      cytosolic mTOR-kinase, associated with the phosphoinositide-3-kinase/Akt pathway.
      After one week of daily sirolimus treatment, initiated on the day of tumour-cell
      inoculation, a dose-response relationship was shown at doses between 0.01
      mg/kg/day and 1 mg/kg/day, decreasing tumour weight from 0.5+/-0.1 g in control
      rats (n=9) to 0.09+/-0.04 g for sirolimus 1 mg/kg (n=9). Treating established
      liver adenocarcinoma (n=15), sirolimus halved the tumour weight (1.4+/-0.2 g vs
      0.7+/-0.1 g, p=0.005). Trough concentration in blood was 6.4+/-0.2 ng/ml after
      five days of daily treatment with 1 mg/kg sirolimus intraperitoneally. At this
      dose, there was no decrease in food consumption or rat weight, but decrease in
      weight of spleen, and increase in weight of liver (p<0.01). The three tumours
      studied, an nitrosoguanidin-induced adenocarcinoma, a Leydig cell sarcoma and a
      hepatoma, all responded, establishing sirolimus as a promising anticancer drug.

PMID- 15868911
TI  - Pre-clinical evaluation of the activity of irinotecan as a basis for regional
      chemotherapy.
AB  - BACKGROUND: Irinotecan alone and in combination with 5-fluorouracil (5-FU)
      displays potent activity in advanced colorectal cancer. The aim of this study was
      to estimate the potential efficacy of irinotecan for hepatic arterial infusion
      (HAI) chemotherapy. MATERIALS AND METHODS: We investigated the anti-proliferative
      effects of irinotecan alone and in combination with 5-FU in HT29 and NMG64/84
      colon and COLO-357, MIA PaCa-2 and PANC-1 pancreatic cancer cell lines and in
      fresh tumors from patients with primary colon cancer (n=2) and colorectal liver
      metastases (n=11) in vitro, using the MTT growth assay and the human tumor colony
      forming assay (HTCA), mimicking conditions which are achievable during HAI.
      RESULTS: Irinotecan displayed concentration- and time-dependent cytotoxic effects
      in all tested cell lines. Treatment of cell lines with irinotecan followed by 5
      FU did not result in synergistic anti-proliferative effects. In the HTCA, the
      sensitivity of each cell line varied depending on the incubation times (30, 90,
      180 and 1440 min). Independent of the individual sensitivity, the IC50
      concentration and time products were lowest when incubating with irinotecan for
      30 min for all cell lines. The IC50 of irinotecan in HT29, NMG64/84, COLO-357,
      MIA PaCa-2 and PANC-1 cells at 30 min were 200, 160, 100, 400 and 150 microg/ml,
      respectively, in the HTCA. All isolated tumor samples displayed concentration
      dependent inhibition of colony formation after exposure to irinotecan for 30 min.
      The IC50 of irinotecan of 5 of the 11 liver metastases was <100 microg/ml.
      CONCLUSION: Irinotecan seems to be suitable for HAI therapy phase II studies. Due
      to the observation that several liver metastases had IC50 values that may be
      clinically achievable by HAI, patients with such tumors may benefit in the future
      from HAI using irinotecan.

PMID- 15868912
TI  - Antiproliferative and antimigratory effects of doxorubicin in human osteosarcoma
      cells exposed to extracellular matrix.
AB  - Osteosarcoma cells are involved in the remodeling of the extracellular matrix
      (ECM) that affects their growth, invasive and metastatic activities. The tumour
      ECM provided effective protection against chemotherapy agents in several
      previously studied malignancies. The current study examined the effects of
      doxorubicin on cells that were migrated into a 3-dimensional extracellular matrix
      gel (ECM-gel) in comparison with its effects on cells remaining in the monolayer
      compartment. A human osteosarcoma cell line (OSCORT) was treated with doxorubicin
      in monolayer culture for 4 or 24 hours, and then overlaid by ECM-gel for 24
      hours. Tumour cells remaining in the monolayer were separated from the cells
      migrated into ECM-gel, and both of them were characterized. OSCORT cells migrated
      into ECM-gel showed elevated levels and activity of topoisomerase II, increased
      protein expression of beta1 integrin and matrix metalloproteinase-9 activity.
      Doxorubicin treatment for 4 hours resulted in increased cytotoxicity in the
      monolayer compartment relative to the cells migrated into ECM-gel, whereas 24
      hour treatment at a low concentration (0.01 microg/ml) showed an antimigratory
      effect. Different antiproliferative and antimigratory effects of doxorubicin
      treatment schedules warrant short-term, high-dose treatment for targeting the
      tumour growth, and long-term, low-dose treatment for targeting the invasion of
      osteosarcoma.

PMID- 15868913
TI  - Urinary trypsin inhibitor suppresses surgical stress-facilitated lung metastasis
      of murine colon 26-L5 carcinoma cells.
AB  - Recently, we have reported that surgical stress promoted the metastasis of murine
      colon carcinoma cells to the lung by inducing the expression of proteases such as
      matrix metalloprotease-9 (MMP-9) in lung tissue. Urinary trypsin inhibitor (UTI)
      is a serine protease inhibitor frequently used to treat pancreatitis and to
      improve the microcirculatory environment. The purpose of this study was to
      investigate the anti-metastatic properties of UTI in an animal model of surgical
      stress-induced cancer metastasis. The intraperitoneal administration of UTI after
      the intravenous injection of colon 26-L5 carcinoma (colon 26-L5) cells into mice
      subjected to surgical stress suppressed the enhancement of lung metastasis
      (p<0.05). Furthermore, we investigated the effect of UTI on tumor growth,
      adhesion to fibronectin, migration, invasion and enzymatic degradation in colon
      26-L5. UTI reduced the invasive ability and the degradation by MMP-9 of gelatin
      substrate in colon 26-L5 cells. UTI may improve therapeutic efficacy in cancer
      patients after major surgery.

PMID- 15868914
TI  - Experimental study on fluorescent microspheres as a tracer for sentinel node
      detection.
AB  - BACKGROUND: Common tracers for sentinel node navigation surgery are blue dye and
      technetium-99m-labelled colloids. However, in most esophageal or lung cancer
      patients, it is impossible to detect the sentinel node among mediastinal nodes by
      blue dye because of the anthracotic pigmentation of mediastinal nodes. The use of
      technetium-99m-labelled colloids requires a special facility, while a large hot
      spot at the injection site prevents detection of the sentinel node around the
      primary lesion. To overcome these problems, we investigated the use of
      fluorescent microspheres (0.1-20 microm in diameter) as tracers in animals and
      detected fluorescence-positive nodes by a simple ultraviolet light irradiation
      method. MATERIALS AND METHODS: Two milliliters of fluorescent microspheres 0.1-20
      microm in diameter diluted to 2.5% weight per volume was injected via the tail
      vein of 30 rats; systemic side-effects were examined. One milliliter of 1.0
      microm-diameter microspheres dilution was injected on the backs of 30 rats; local
      side-effects were examined. A microsphere dilution (0.2 ml, 1.0 microm-diameter
      microspheres) was injected into the footpad of 18 rats; the lymphatic pathway and
      drainage were examined. Five milliliters of 1.0 microm-diameter fluorescent
      microspheres was injected endoscopically into the submucosa of the esophagus,
      stomach and small and large bowels of 6 domestic pigs, and 5 ml was injected into
      the subadventitia of the esophagus or subserosa of the stomach, and small and
      large bowels. Fluorescence-positive lymph ducts or nodes were carefully observed
      under ultraviolet light irradiation. RESULTS: No systemic side-effects were
      observed in rats. Only mild edema and a mild inflammatory reaction were observed
      on the backs of rats. Fluorescent microspheres 0.1, 0.5 and 1.0 microm in
      diameter were detected in lymph ducts or nodes of pigs within 1 hour after
      injection. CONCLUSION: Sentinel node navigation surgery with the use of
      fluorescent microspheres might be feasible and advantageous for patients with
      esophageal or lung cancer, especially in the mediastinum.

PMID- 15868915
TI  - HER2-specific cytotoxic activity of lymphokine-activated killer cells in the
      presence of trastuzumab.
AB  - We investigated whether trastuzumab, a humanized anti-HER2 monoclonal antibody,
      could induce HER2-specific cytotoxic activity on lymphokine-activated killer
      (LAK) cells. Trastuzumab alone was not toxic to the HER2-positive breast cancer
      cell lines MDA-MB453 and ZR75-1, nor to the HER2-negative breast cancer cell
      lines MDA-MB468 and MCF-7. LAK cells, which were activated with 1000 U/ml IL-2
      for 4 days (4-day LAK), showed cytotoxic activity against the MDA-MB453, ZR75-1
      and MCF-7 cells, but not against MDA-MB468 cells. LAK cell cytotoxic activity
      against the HER2-positive breast cancer cell lines MDA-MB453 and ZR75-1 was
      significantly augmented in the presence of 10 nM trastuzumab, but that against
      the HER2-negative breast cancer cell lines MDA-MB468 and MCF-7 was not. The
      cytotoxic activity of LAK cells plus trastuzumab against the MDA-MB453 cells was
      significantly inhibited by the addition of cold MDA-MB453 cells or cold ZR75-1
      cells, but not by addition of cold MDA-MB468 cells. Twenty-nine percent of the 4
      day LAK cells were CD16+, and the cytotoxicity of LAK cells plus trastuzumab was
      abrogated with the anti-CD16 antibody treatment of the LAK cells in the
      cytotoxicity assay. Only 7% of the 10-day LAK cells were CD16+, and the 10-day
      LAK cells failed to exhibit cytotoxicity even with trastuzumab. These results
      suggest that HER2-specific cytotoxic activity, which is mediated by an antibody
      dependent cellular cytotoxicity (ADCC) mechanism, can be induced on LAK cells by
      the addition of trastuzumab.

PMID- 15868916
TI  - Expression of p8 protein in breast carcinoma; an inverse relationship with
      apoptosis.
AB  - BACKGROUND: P8 is a transcription factor and its expression is elevated in
      response to apoptotic stimuli. However, p8 in human carcinoma tissue has not been
      investigated in depth. In this study, we investigated p8 expression in breast
      carcinoma. MATERIALS AND METHODS: We immunohistochemically investigated p8
      expression in 50 cases of breast carcinoma, including 7 non-invasive ductal
      carcinomas. RESULTS: High expression of p8 was observed in 60% of cases, which
      was inversely related to tumor size and UICC stage. All non-invasive ductal
      carcinomas diffusely expressed p8. Furthermore, in tumors of 2 cm or larger, the
      p8 expression was inversely linked to the apoptotic index. CONCLUSION: These
      results suggest that p8 plays a role in the early phase of breast carcinoma
      progression and especially in tumors of larger size, acting as an inhibitor of
      apoptosis of breast carcinoma cells.

PMID- 15868917
TI  - Effective treatment of perianal tumors in dogs with electrochemotherapy.
AB  - BACKGROUND: Electrochemotherapy is an antitumor therapy that utilizes locally
      delivered, short intense direct current electric pulse to the tumor nodule plus
      chemotherapy. The aim of the present study was to evaluate the
      electrochemotherapy treatment of perianal tumors of different sizes in dogs.
      MATERIALS AND METHODS: In 12 dogs, 26 tumor nodules of perianal tumors of
      different size, and clinically expected to be of different histological type,
      were treated with electrochemotherapy. Electrochemotherapy consisted of
      intratumoral injection of cisplatin (1 mg/cm3) or bleomycin (3 mg/cm3), followed
      by application of electric pulses (8 electric pulses; amplitude, 910 V, duration,
      100 micros, frequency, 1 Hz) to the tumor nodule. RESULTS: Responses to treatment
      were assessed 4 weeks after the therapy; 82% of all tumors treated with
      electrochemotherapy responded with objective response (OR) (complete response
      (CR)=41%, partial response (PR)=41%), 16% responded with no change (NC) and 1
      tumor (2%) went to progressive disease (PD). At the end of the observation period
      for each tumor, ranging from 1 to 34 months, 92% OR (CR=65%, PR=27%), 8% NC and
      no PD were obtained. No major local or general side-effects were noted.
      CONCLUSION: Electrochemotherapy with cisplatin or bleomycin is an effective
      treatment of perianal tumors in dogs. The advantages of this therapy are its
      simplicity, short duration of treatment sessions, low chemotherapeutic doses and
      insignificant side-effects, as well as the fact that the subject does not have to
      stay in hospital.

PMID- 15868918
TI  - Platelet factor 4 gene transfection into tumor cells inhibits angiogenesis, tumor
      growth and metastasis.
AB  - Tumor growth and metastasis depend on angiogenesis, which is triggered by a
      chemical signal from the tumor cells to resting endothelial cells which then
      enter into a phase of rapid growth. Platelet Factor 4 (PF4) inhibits endothelial
      proliferation in vitro and angiogenesis in vivo. PF4 also inhibits tumor growth,
      however, as with other angiogenesis inhibitors, sustained tumor growth inhibition
      requires prolonged exposure to the recombinant protein. In this study, Lewis lung
      carcinoma (LLH) cells were transfected with the human PF4 via mammalian
      expression vectors and the ability of the transfected cells to form tumors and
      metastasis in vivo was evaluated. To evaluate the tumor growth rate of PF4
      transfected (LLH/PF4) or control (LLH/neo) cells in vivo, we injected LLH/PF4 or
      LLH/neo cells subcutaneously (s.c.) or intravenously (i.v.). In the s.c. assay,
      LLH/PF4 had no significant effect on tumor growth. Conversely, in the i.v. assay,
      PF4 significantly reduced the number of lung metastasis (p=0.019) and weight
      (p=0.056). The inhibition of lung metastasis suggests that PF4 may inhibit tumor
      associated neovascularization, and may prevent the affinity of tumor cells for
      the normal lung tissue.

PMID- 15868919
TI  - Neuroendocrine differentiation in primary Merkel cell carcinoma--possible
      prognostic significance.
AB  - BACKGROUND: The aim of this study was to examine the level of neuroendocrine
      differentiation to determine its association with clinicopathological parameters.
      PATIENTS AND METHODS: Twenty-five primary MCC samples were evaluated for
      neuroendocrine differentiation profiles by immunohistochemistry using antibodies
      to chromogranin-A, microtubule associated protein-2 and synaptophysin. The data
      were compared with clinical parameters to find out whether their expression
      correlates with prognosis. RESULTS: In general, MCC shows a high degree of
      neuroendocrine differentiation. A higher expression of chromogranin-A and
      synaptophysin associated with benign behaviour. Chromogranin-A appeared to be the
      most important one in predicting the course of disease. CONCLUSION: Low levels of
      neuroendocrine differentiation in MCC associates with poor prognosis.
      Chromogranin-A could be used to identify patients who might benefit from
      oncological treatments.

PMID- 15868920
TI  - Modified arabinoxylan rice bran (MGN-3/Biobran) enhances yeast-induced apoptosis
      in human breast cancer cells in vitro.
AB  - We have recently reported that phagocytosis of killed Saccharomyces cerevisiae,
      baker's yeast, induced apoptosis in human breast cancer cell lines MCF-7, ZR-75-1
      and HCC70. In this study we have evaluated the effect of treatment with MGN-3, a
      modified arabinoxylan from rice bran, on phagocytosis and yeast-induced apoptosis
      in breast cancer cells. Cancer cells were cultured with yeast at a ratio of 1:10
      in the absence or presence of MGN-3, and the percentages of phagocytic and
      apoptotic cancer cells were examined by flow cytometry and by cytospin
      preparations. Cancer cells treated with MGN-3 exhibited increased percentages of
      attachment (200%) and uptake of yeast (313%) by MCF-7 cells at 0.5 hr, as
      compared with cells without MGN-3. In addition, treatment with MGN-3 resulted in
      a 2 fold increase in the percentage of apoptotic MCF-7 cells, 2.5 fold for ZR-75
      cells and 1.8 fold for HCC70 cells. MGN-3 effect was dose-dependent and
      associated with increased activation of caspases 8 and 9 in MCF-7 cells, and
      caspases 8, 9 and 3 in HCC70 cells. This data demonstrates that MGN-3 accelerates
      phagocytosis-induced apoptosis of cancer cells, which may represent a novel
      therapeutic strategy for the treatment of breast cancer.

PMID- 15868921
TI  - Decreased MCF-7 breast cancer cell proliferation by serum from a selected line of
      beef cattle.
AB  - One way to combat or treat breast cancer, the most common cancer among women, is
      to decrease or prevent proliferation of cancerous cells. Many animal species of
      agricultural importance have been selected for various growth traits, typically
      through altered proliferative capacity of some cell types. Previous studies in
      two lines of cattle divergently selected for serum IGF-I concentration have shown
      that low IGF-I cattle had increased growth rates and high IGF-I cattle had
      decreased growth rates. Serum from either the high or low IGF-I lines of cattle
      were administered to MCF-7 breast cancer cell lines and doubling times were
      determined. The MCF-7 cells treated with serum from cattle with high serum IGF-I
      concentrations took 26% longer to double than MCF-7 cells treated with serum from
      cattle with low serum IGF-I concentrations. In conclusion, model systems
      employing agricultural animals may provide novel insight into mechanisms of cell
      proliferation.

PMID- 15868922
TI  - Biological effect of irradiation on adhesion molecules in human colon cancer
      cells in vitro.
AB  - BACKGROUND: Carbohydrate antigens, such as sialyl Lewis(a) antigen (s-Le(a)) and
      sialyl Lewis(x) antigen (s-Le(x)), play an important role in cancer metastasis in
      vitro and in vivo. Currently, preoperative radiotherapy is used to prevent local
      recurrence of rectal cancer. We investigated the effects of X-ray irradiation on
      the carbohydrate antigens s-Le(a) and s-Le(x) in vitro. MATERIALS AND METHODS:
      The cell surface expressions of s-Le(a) and s-Le(x) were determined by flow
      cytometric analysis at 24 hours after X-ray irradiation of 4 human cancer cell
      lines. s-Le(a) and s-Le(x) functions were quantitated using a monolayer cell
      adhesion assay with human umbilical vein endothelial cells (HUVECs). RESULTS: The
      cell surface expressions of s-Le(a) and s-Le(x) decreased at 24 hours after
      irradiation. s-Le(a) adhesion to HUVECs monolayers similarly decreased at 24
      hours after irradiation. CONCLUSION: These results may indicate a role for X-ray
      irradiation in the reduction of liver metastasis in patients with colon cancer.

PMID- 15868923
TI  - A potential for tissue restrictive gene therapy in renal cell carcinoma using
      MN/CA IX promoter.
AB  - BACKGROUND: The expression of the MN/carbonic anhydrase IX (CA IX) protein is
      detected in renal cell carcinoma (RCC). A tumor-specific MN promoter was designed
      and evaluated. MATERIALS AND METHODS: Western blot, reverse transcription-PCR and
      Northern blot for MN expression were performed on Hela cells, LNCaP and four
      human RCC cell lines. The MN promoter (554 bp) was cloned into pGL3 luciferase
      reporter vectors and their activities were tested. RESULTS: Hela cells, SKRC-31
      and SKRC-38 expressed high levels of MN RNA and MN protein. The MN promoter has 5
      to 10-fold higher activity in MN-positive cell lines than in MN-negative cell
      lines. It could enhance the activity of the basic SV40 early promoter (6 to 25
      fold) in MN-positive cells but not in MN-negative cells. CONCLUSION: MN
      expression in RCC may derive from altered expression of transcriptional
      factor(s), which binds to the MN enhancer element, and can be used for tumor
      specific toxic gene therapy for RCC.

PMID- 15868924
TI  - Induction of tumor-specific cytotoxicity and apoptosis by doxorubicin.
AB  - Doxorubicin (adriamycin), an anthracycline antibiotic, showed higher cytotoxic
      activity against human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC
      3, submandibular gland carcinoma HSG, promyelocytic leukemia HL-60) than against
      normal human cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament
      fibroblast HPLF). Doxorubicin activated caspases 3, 8 and 9 in both HSC-2 and HL
      60 cells, but induced internucleosomal DNA fragmentation only in HL-60 cells.
      Western blot analysis showed that doxorubicin did not significantly change the
      intracellular concentration of Bcl-2, Bax and Bad in HL-60 cells. Real-time PCR
      analysis showed that HPC cells expressed the highest amount of mdr1 mRNA,
      followed by HSC-2 > HGF > HSC-3 > HPLF > HSG > HL-60. ESR spectroscopy showed
      that doxorubicin produced no discernible radical under alkaline conditions (pH
      7.4 to 10.5) except at pH 12.5, and it did not scavenge O2-, NO and DPPH
      radicals. The present study demonstrates that doxorubicin induces the tumor
      specific cytotoxicity and some, but not all, apoptosis markers possibly by a
      radical-independent mechanism, and that mdr1 expression in the tumor cells is not
      related to the tumor specificity of doxorubicin.

PMID- 15868925
TI  - Dextran sulfate suppresses cell adhesion and cell cycle progression of melanoma
      cells.
AB  - We have reported that dextran sulfate is a possible candidate for an
      antimetastatic drug because it inhibits cell adhesion. It has been demonstrated
      that dextran sulfate can detach cancer cells adhering to the bottom of plastic
      flasks, and that the detached cells do not readhere or proliferate. In this
      study, we investigated the effects of dextran sulfate on cancer cells, focusing
      on cell cycle regulators as well as cell adhesion molecules. The effects of
      dextran sulfate on the cell cycle were examined by flow cytometry, and changes in
      gene expression caused by dextran sulfate were analyzed by cDNA microarray to
      identify changes in adhesion and cell cycle genes. By flow cytometry, treatment
      with dextran sulfate increased the percentage of cells in the G1/G0-phase, and
      decreased those in the S- and G2/M-phases. Analysis by cDNA microarray revealed
      decreased expression of several genes essential for progression of the G1- and S
      phases. The expression of the adhesion factors involved in metastases was also
      suppressed. Furthermore, we confirmed these changes in the gene expression by
      Northern and Western blotting. Our results indicate that dextran sulfate
      suppresses cell adhesion and cell cycle progression, both of which are essential
      for metastasis, suggesting that dextran sulfate could be used as an
      antimetastatic agent.

PMID- 15868926
TI  - Gastric hamartomatous tumours in a transgenic mouse model expressing an activated
      dioxin/Ah receptor.
AB  - BACKGROUND: The dioxin/Aryl hydrocarbon (Ah) receptor is a ligand-activated
      transcription factor known to mediate the toxic effects of the environmental
      pollutants dioxins. MATERIALS AND METHODS: Transgenic mice expressing a
      constitutively active Ah receptor were found to develop gastric tumours. RESULTS:
      Segments of the normal gastric glands of the corpus region (lined by foveolar,
      parietal and cardio-pyloral cells) developed cystic tumours. Tumours in the
      submucosa and muscularis propria consisted of large cysts surrounded by organized
      lymphocytic, connective, squamous and adipose tissues and vessels. Those tumours
      were obviously hamartomatous in nature. Despite the fact that the tumours had an
      inward growth and penetrated all stomach layers, no metastases developed.
      CONCLUSION: The model here described may open new vistas into the investigation
      of the role of environmental pollutants in the development of gastric hamartomas.

PMID- 15868927
TI  - Allelic imbalance on distal 7q (7q36.1-q36.3) in gastric cardia and oesophageal
      (Barrett's) adenocarcinoma.
AB  - BACKGROUND: Oesophageal (Barrett's) and gastric cardia adenocarcinomas are
      cancers arising at and around the gastro-oesophageal junction. The prognosis is
      poor, since detection is usually at a late stage and metastatic spread occurs
      early. MATERIALS AND METHODS: We investigated the 7q region with a set of 5
      polymorphic markers spanning 7q36.1-q36.3 in 33 Barrett-related carcinomas. In
      addition, 40 gastric cardia cancers were investigated to compare the pattern of
      imbalance at these loci. RESULTS: Overall, the number of allelic loss was higher
      in Barrett's cancers than in gastric cardia carcinomas (p=0.04). In Barrett's
      adenocarcinomas, imbalance varied from 28% to 45% (of informative cases) with the
      highest prevalence at marker D7S483. In gastric cardia cancers, loss ranged from
      12% to 27% (of informative cases), being most frequent at marker D7S3037. The
      difference between oesophageal and gastric adenocarcinomas was highest for
      polymorphic marker D7S483 (p=0.05). CONCLUSION: Marker D7S483 can aid in
      discriminating oesophageal (Barrett's) and gastric cardia carcinomas. Further,
      this region possibly harbours cancer gene(s) involved in Barrett-related
      adenocarcinomas.

PMID- 15868928
TI  - 5-FU uptake in peritoneal metastases after pretreatment with radioimmunotherapy
      or vasoconstriction: an autoradiographic study in the rat.
AB  - This study was conducted to test if tumour drug uptake could be increased in
      experimental colorectal cancer peritoneal metastases, by using pretreatment with
      peritoneal vasoconstriction or radioimmunotherapy. A total of 29 nude rats with
      peritoneal metastases were injected intraperitoneally (i.p.) with 14C-labelled 5
      FU. The animals were randomly allocated to 5 groups. Six days prior to 5-FU,
      group I (control) received i.p. NaCl, group II was subjected to i.p.
      radioimmunotherapy (RIT) 131I-labelled anti-CEA monoclonal antibody (150 MBq) and
      group III received i.p. Norbormide 10 minutes before 5-FU. Two days prior to 5-FU
      group IV and V received i.p. NaCl (control) and RIT, respectively. 5-FU uptake
      was visualised with autoradiography and quantified by computer-based image
      analysis. Tumours in group III showed a higher uptake (mean+/-SD, 21.4+/-17) than
      in group I (11.8+/-10, p=0.04). This was also true when the analysis was
      restricted to larger tumours (> or = median 627 pixels) group III (23.2+/-19) vs.
      group I (11.8+/-7, p=0.002). Peritoneal tumours in group II were of smaller size
      (median area 308 pixels) than in group I (619 pixels), in group III (901 pixels),
      in group IV (769 pixels) and in group V (808 pixels). RIT decreased the tumour
      size whereas it did not affect 5-FU uptake. The uptake of 5-FU was potentiated by
      pretreating the animals with Norbormide. These results demonstrate that 5-FU
      uptake in experimental peritoneal metastases is increased when the peritoneal
      absorption of the drug is blocked using pretreatment with a vasoconstrictive
      agent. This principle may also be relevant when treating patients with colorectal
      cancer peritoneal metastases.

PMID- 15868929
TI  - Thymidylate synthase and dihydropyrimidine dehydrogenase in non-small cell lung
      cancer: relationship between mRNA expression and activity.
AB  - BACKGROUND: UFT (Tegafur + Uracil) has been reported to be effective for
      postoperative adjuvant chemotherapy of non-small cell lung cancer (NSCLC) in a
      randomized prospective study. Recently, many clinical studies have demonstrated
      that UFT is effective for cancer with a low activity of thymidylate synthase (TS)
      and dihydropyrimidine dehydrogenase (DPD). In the present study, we investigated
      TS and DPD activity in resected tumors and corresponding normal lungs and the
      relationship between the activity and the mRNA expression of TS and DPD in NSCLC.
      MATERIALS AND METHODS: Seventy-seven patients underwent complete surgical
      resection and lymph node dissection for NSCLC. The activity of TS was determined
      by the FdUMP binding assay combined with gel filtration. The activity of DPD was
      determined by radio-enzymatic assay. Tumor tissues and their paired non-cancerous
      tissues were assayed. Furthermore, the mRNA expressions of TS and DPD were
      examined by real-time RT-PCR. RESULTS: The mean TS and DPD activities in NSCLC
      were approximately 2.4-fold and 5-fold of those in normal lungs. The mean TS and
      DPD activities of NSCLC were 0.099 pmol/mg and 407 pmol/mg/min, respectively.
      Although both TS and DPD activities showed a tendency to be high for
      adenocarcinoma, there was no significant difference between TS and/or DPD
      activities and any clinical findings (age, gender, stage and histological type).
      The mRNA expression of DPD was correlated with DPD activity (rs=0.846, p<0.001).
      The mRNA expression of TS was weakly correlated with TS activity (rs=0.757,
      p<0.001). CONCLUSION: TS and DPD activities in NSCLC were higher than those in
      normal lungs. Assay of DPD mRNA and TS mRNA by real-time RT-PCR can be used as an
      indicator for the use of UFT.

PMID- 15868930
TI  - Evaluation of chemosensitivity testing with highly purified tumor cells in 435
      patients with gastric carcinoma using an MTT assay.
AB  - BACKGROUND: We evaluated the results of chemosensitivity testing for gastric
      cancer using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
      (MTT) assay in terms of the correlation of chemosensitivity and
      clinicopathological findings. PATIENTS AND METHODS: We analyzed 435 consecutive
      patients with gastric cancer treated between January 1991 and January 2002.
      Highly purified fresh human gastric cancer cells were obtained from 485 lesions
      including 415 primary tumors and 70 metastatic tumors. RESULTS: CDDP and 5-FU
      were more potent drugs than MMC, ADR and VP-16. The chemosensitivity of
      metastatic tumors was lower than that in primary tumors. The chemosensitivity in
      differentiated cancer was equivalent to that in undifferentiated cancer. The
      manner of tumor invasion and clinical stage affected chemosensitivity for some
      drugs. CONCLUSION: Our results suggest that individual chemosensitivity testing
      is essential to individualize chemotherapy for gastric cancer.

PMID- 15868931
TI  - Evaluation of HER2 gene status in breast cancer by chromogenic in situ
      hybridization: comparison with immunohistochemistry.
AB  - BACKGROUND: The purpose of this study was to evaluate HER2 gene status in
      relation to chromosome 17 polysomy with the chromogenic in situ hybridization
      (CISH) technique and to compare the results with those of immunohistochemistry
      (IHC). METHODS AND RESULTS: Sixty six cases of breast carcinoma with an
      immunohistochemical HER2 protein score of 1+, 2+ 3+ (HercepTest) were
      investigated. HER2 gene status was evaluated on paraffin sections with the CISH
      technique using a digoxigenin-labeled DNA probe. In HER2 positive cases with low
      level amplification (LLA), the copy number of chromosome 17 was determined.
      Thirty four tumors (51.5%) were negative and 32 (48.5%) were positive for HER2
      gene amplification. Of these 10 tumors (15%) showed LLA and 22 tumors (33.5%)
      high level amplification (HLA). Nine of ten tumors with LLA had an equal or
      greater than two ratio of HER2 to chromosome 17 signals. The correlation of the
      results obtained by CISH and IHC showed that the concordance of the two methods
      was highest in the 3+ group (100%) and lower in 1+ group (89%), whereas a high
      degree of discordance was found in the 2+ group (69%). CONCLUSIONS: CISH is an
      accurate and practical technique for the evaluation of both HER2 gene and
      chromosome 17 status and its application is considered necessary especially for
      the clarification of the 2+ results of IHC.

PMID- 15868932
TI  - Osteogenic progenitor cell potency after high-dose chemotherapy (COSS-96).
AB  - BACKGROUND: Since the first trial of chemotherapy in patients with osteosarcoma
      the survival rate has gradually improved. For more than two decades, most
      osteosarcoma patients from Germany, Austria and Switzerland have been treated
      according to the protocols of the Cooperative Osteosarcoma Study Group (COSS).
      The uniform treatment concept of a high-dose polychemotherapy pre- and
      postoperatively improved the survival rate of these patients significantly. One
      severe side-effect of COSS chemotherapy is multiple osteonecrosis. PATIENTS AND
      METHODS: In this study the osteogenic stem cell potency of three different tissue
      types was elucidated after COSS-96 chemotherapy (high-risk arm). Mononuclear
      cells were obtained from the periosteum, cartilage and bone marrow of a 17-year
      old female with a chondroblastic osteosarcoma. The cells were cultivated for 4
      weeks in standard medium and stimulated for osteogenic differentiation after the
      second passage with dexamethasone, glycerolphosphate and ascorbine acid. Two
      weeks later, the cell cultures were analysed with respect to cell morphology and
      immunochemical stainings. RESULTS: All cells cultures showed an osteoblastic
      regeneration potential measured by osteocalcin (OC), osteopontin (OP) and
      alkaline phosphatase (ALP) expression. Compared to other donor tissues and
      localizations, the fibula periosteum showed significantly higher osteoblast rates
      in vitro, whereas collagen II, CD34 and CD45 were not expressed in any culture.
      CONCLUSION: The results of this study demonstrate the survival of mesenchymal
      progenitor cells in bone marrow during COSS-96 polychemotherapy, which allows for
      an osteogenic regeneration in vitro and potentially in vivo.

PMID- 15868933
TI  - Differential expression of VEGF isoforms and VEGF receptors in cartilaginous
      tumors.
AB  - Vascular endothelial growth factor (VEGF), which is known to have at least five
      isoforms and four receptors, is integral to tumor-induced neovascularization. In
      order to determine whether VEGF signaling is modulated in the development of
      cartilaginous tumors, we analyzed osteochondrogenic tumors for the expression of
      VEGF isoforms and VEGF receptors using the reverse transcription-polymerase chain
      reaction method. Although mRNA for VEGF121, VEGF165, VEGFR-1 and NRP-2 was widely
      expressed, mRNA expression for VEGF189, VEGFR-2 and NRP-1 was linked to a
      malignant phenotype such as local invasion. These results indicated that VEGF
      signaling was fine-tuned by the differential expression of the VEGF isoforms and
      VEGF receptors.

PMID- 15868934
TI  - Baicalein induced cell cycle arrest and apoptosis in human lung squamous
      carcinoma CH27 cells.
AB  - Baicalein, a flavonoid compound, is one of the active constituents of the root of
      Scutellariae Radix. Baicalein inhibited the growth of human lung squamous
      carcinoma CH27 cells in a dose-dependent manner. Cell cycle analysis revealed an
      increase in the S-phase cell population following 24-h exposure to 50 microM
      baicalein. During the S-phase arrest, analysis of cell cycle regulatory molecules
      demonstrated that baicalein decreased the levels of cdk 4, cyclin B1 and cyclin
      D1. Furthermore, baicalein (50 microM) significantly induced cell apoptosis after
      3 days of treatment. Baicalein induced apoptosis, as confirmed by condensed
      nuclei and DNA fragmentation, in CH27 cells. Baicalein-induced apoptosis was also
      accompanied by a decrease in Bcl-2 and caspase-3 proform levels. These results
      suggest that baicalein inhibits the proliferation of CH27 cells via S-phase
      arrest and apoptosis.

PMID- 15868935
TI  - Kinetic evaluation of polyamines as radical scavengers.
AB  - To clarify whether polyamines scavenge alkyl (carbon-centered) and peroxy (oxygen
      centered) radicals, we analyzed their effects on the kinetics of polymerization
      of methyl methacrylate (MMA) induced by 2,2'-azobisisobutyronitrile (AIBN, a R*
      radical) and benzoyl peroxide (BPO, a PhCOO* radical) under nearly anaerobic
      conditions. Stoichiometric factors (n; number of free radicals trapped by one
      mole of antioxidant moiety) were determined by the induction period method. The n
      value for polyamines (putrescine, spermidine and spermine) was 0.1-0.7, whereas
      that for conventional synthetic antioxidants, BHA and BHT, was about 2. These n
      values were not different between the AIBN and BPO systems. The n value for
      polyamines declined in the order spermine > spermidine > putrescine. The
      K(inh)/K(p) value for polyamines (20-115) was greater than that (4-7) for BHT or
      BHA. Radical-scavenging activity largely depends on the stoichiometric factor of
      antioxidants rather than their effects on initial rate of polymerization, a rate
      of propagation. Polyamines may scavenge alkyl or peroxy radicals derived from
      polyunsaturated fatty acids in biological systems.

PMID- 15868936
TI  - Ellagic acid induced p53/p21 expression, G1 arrest and apoptosis in human bladder
      cancer T24 cells.
AB  - It is well known that dietary phenolic compounds can elicit vital cellular
      responses such as cytotoxicity, cell cycle arrest and apoptosis by activating a
      cascade of molecular events. Ellagic acid is one of these phenolic compounds, but
      the exact mechanism of its action is still unclear. The objective of this study
      was to investigate ellagic acid-induced cell cycle arrest and apoptosis in T24
      human bladder cancer cells in vitro. Assays were performed to determine cell
      viability, cell cycle arrest, apoptosis, caspases-3 activity and gene expression,
      measured by flow cytometric assay, polymerase chain reaction (PCR) and
      determination of caspase-3 activity. Ellagic acid significantly reduced the
      viable cells, induced G0/G1-phase arrest of the cell cycle and apoptosis. Ellagic
      acid also increased p53 and p21 and decreased CDK2 gene expression, that may lead
      to the G0/G1 arrest of T24 cells. Ellagic acid also promoted caspase-3 activity
      after exposure for 1, 3, 6, 12 and 24 h, which led to induction of apoptosis.
      Furthermore, the ellagic acid-induced apoptosis on T24 cells was blocked by the
      broad-spectrum caspase inhibitor (z-VAD-fmk).

PMID- 15868937
TI  - Human squamous cell carcinoma of the tongue and colon undergoes apoptosis upon
      phagocytosis of Saccharomyces cerevisiae, the baker's yeast, in vitro.
AB  - The present study was carried out to evaluate the effect of phagocytosis of
      killed yeast on the induction of apoptosis in two human solid tumors of the
      gastrointestinal (GI): the squamous cell carcinomas of the tongue (SCCA) are (SCC
      4 and SCC-9) and the adenocarcinomas of the colon (ADENOCA) are (Caco-2 and DLD
      1). Cancer cells were cultured with heat killed Saccharomyces cerevisiae, baker's
      and brewer's yeast, at ratio of yeast to cancer cells = 10:1. The percentage of
      tumor cells that had attached/phagocytosed yeast and oxidative burst was
      determined by using oxidative sensitive dye (DCFH-DA) and flow cytometry. SCC-4
      and colon Caco-2 cells demonstrated initial high levels of phagocytosis that
      peaked (35.8-52.8%) at 2 hr. The oral SCC-9 and colon DLD-1 cells demonstrated
      low phagocytic activity (7-12%). Phagocytosis was not associated with oxidative
      burst. Upon phagocytosis of yeast, cancer cells underwent apoptosis that was
      maximized at 4 hr. Yeast-induced apoptosis was significant in SCC-4 (45%), as
      compared with SCC-9 cells (17%), and Caco-2 (76%), as compared with DLD cells
      (12%). Apoptosis in cancer cells was inhibited by caspase inhibitor, Z-VAD-FMK;
      this suggests that caspases may be involved in apoptosis of the GI cancers. This
      data may have clinical implications for the treatment of solid tumors.

PMID- 15868938
TI  - Arsenic trioxide circumvents multidrug resistance based on different mechanisms
      in human leukemia cell lines.
AB  - To determine the antitumor effect of arsenic trioxide (As2O3) on multidrug
      resistant cells, we applied 3 human leukemia cell lines: daunorubicin (DNR)
      resistant cell line K562/D1-9, which overexpresses p-glycoprotein (Pgp); DNR and
      1-beta-D-arabinofuranosylcytosine (Ara-C) double-resistant cell line HL60/AD,
      which overexpresses multidrug resistance-associated protein (MRP1); and Bcl-2
      transfected pre-B lineage leukemia cell line 697/Bcl-2. Interestingly, K562/D1-9
      showed collateral sensitivity. Only HL60/AD showed small cross resistance, but
      697/Bcl-2 had no resistance to As2O3. An intracellular content of glutathione
      (GSH) played a critical role in sensitivity to As2O3. Buthionine-sulfoximine
      (BSO), which reduces the GSH content, not only increased the As2O3 sensitivity
      but also conquered the MRP1-related cross resistance in HL60/AD. In conclusion,
      As2O3 was effective in all 3 cell lines, suggesting that As2O3 may be a promising
      agent for the treatment of multidrug-resistant leukemia.

PMID- 15868939
TI  - Involvement of Bax, Bcl-2 and caspase 3 in hydroxyurea- or etoposide-induced
      apoptosis of mouse interleukin-3-dependent lymphoma cells.
AB  - BACKGROUND: The apoptosis action induced by hydroxyurea or etoposide in
      interleukin 3-dependent lymphoma cells (DA-1) was studied. MATERIALS AND METHODS:
      The conditions to study apoptosis of these cells were 17 hours of cell treatment
      with concentrations of 1.25 mM hydroxyurea or 100 microM etoposide using flow
      cytometry, fluorometry and immunoblots techniques. RESULTS: Time-dependent
      reductions of cell viability after these treatments were observed. Caspase 3
      activity was highly activated in both cases. Chemical treatments or interleukin 3
      withdrawal rendered level changes in Bax and Bcl-2 expression. CONCLUSION: These
      results support the implication of these factors in DA-1 cell apoptosis induced
      by these chemical treatments or interleukin 3 depletion.

PMID- 15868940
TI  - Transmission electron microscopy study of the effects produced by wide-band low
      power millimeter waves on MCF-7 human breast cancer cells in culture.
AB  - Our previous work showed that low-power wide-band millimeter waves (MMW) inhibit
      the growth of the MCF-7 human breast carcinoma cell line, also causing a marked
      reduction of the density of microvilli at the apical membrane of the MCF-7 cells,
      as revealed by scanning electron microscopy. The aim of the present work was to
      investigate the ultrastructural changes induced by such electromagnetic
      radiations on this cell line. A transmission electron microscopy study was
      performed on MCF-7 cells irradiated under the same experimental conditions
      previously adopted. Transmission electron microscopy analysis revealed several
      ultrastructural features of the MMW-irradiated cells pertinent to cells subjected
      to sublethal injury. The antiproliferative effect of the millimeter radiation was
      confirmed. MMW, in the 52-78 GHz frequency range, act as stress factor on the
      cells that survive in a non-steady low-mitogenetic metabolic state.

PMID- 15868941
TI  - Interleukin-12 has no effect on vascular density, perfusion, hypoxia and
      proliferation of an implanted human squamous cell carcinoma xenograft tumour
      despite up-regulation of ICAM-1.
AB  - BACKGROUND: Interleukin-12 is an anti-angiogenic and antitumor agent in many
      transplanted murine tumour models. In a previous clinical study in head and neck
      squamous cell carcinoma patients treated with rhIL-12 the tumour turned pale,
      after an initial reddening. The aim of this study was to investigate the effects
      of rmIL-12 on the vasculature, blood perfusion, hypoxia and proliferation of
      tumour cells in an implanted human head and neck squamous cell carcinoma
      xenograft tumour, with a relatively large diameter, in Balb/c nu/nu mice over
      time. MATERIALS AND METHODS: Established human squamous cell carcinoma xenograft
      tumours were intratumorally injected for 3 days with either 200 ng rmIL-12 or
      PBA. Mice were sacrificed at 4 different time points (between 8 hours and 8 days
      after the last injection), after administration of Pimonidazole, BrdUrd and
      Hoechst 33342. The tumour sections were quantitatively analysed with a semi
      automatic method based on a computerised digital image analysis system, after
      immunohistochemical staining. RESULTS: Despite a faster and higher up-regulation
      of anti-mouse ICAM-1 in the IL-12-treated tumours, no significant differences in
      vascular density, perfusion fraction, hypoxic fraction and BrdUrd labelling index
      were detected between IL-12-treated tumour and control tumours. CONCLUSION: We
      suggest that the main reason why the observation made in humans could not be
      confirmed in this mice study is the combination of a lack of an intact immune
      system in the Balb/c nu/nu mice and a relatively large tumour with probably a lot
      of mature vessels.

PMID- 15868942
TI  - Frequency and irradiation time-dependant antiproliferative effect of low-power
      millimeter waves on RPMI 7932 human melanoma cell line.
AB  - The biological effects produced by low power millimeter waves (MMW) were studied
      on the RPMI 7932 human melanoma cell line. Three different frequency-type
      irradiation modes were used: the 53.57-78.33 GHz wide-band frequency range, the
      51.05 GHz and the 65.00 GHz monochromatic frequencies. In all three irradiation
      conditions, the radiation energy was low enough not to increase the temperature
      of the cellular samples. Three hours of radiation treatment, applied every day to
      the melanoma cell samples, were performed at each frequency exposure condition.
      The wide-band irradiation treatment effectively inhibited cell growth, while both
      the monochromatic irradiation treatments did not affect the growth trend of RPMI
      7932 cells. A light microscopy analysis revealed that the low-intensity wide-band
      millimeter radiation induced significant morphological alterations on these
      cells. Furthermore, a histochemical study revealed the low proliferative state of
      the irradiated cells. This work provides further evidence of the
      antiproliferative effects on tumor cells induced by low power MMW in the 50-80
      GHz frequency range of the electromagnetic spectrum.

PMID- 15868943
TI  - Diagnostic evaluation of carbon tetrachloride-induced rat hepatic cirrhosis
      model.
AB  - BACKGROUND: To find a non-invasive method of diagnosing hepatic fibrosis and
      cirrhosis, we evaluated the relationship of the hepatic cirrhosis grade between
      histopathology and mean grey level (MGL) in B-mode ultrasonography in CCl4
      induced liver cirrhosis. MATERIALS AND METHODS: Three groups of rats were treated
      with olive oil, CCl4, and CCl4 + silymarin. Rats were sacrificed at weeks 4, 8
      and 12, after B-mode ultrasonography examination, and then analyzed
      histopathologically for fatty change and fibrosis. RESULTS: On the grade of
      fibrosis, the CCl4 group showed higher value at 8 and 12 weeks than the silymarin
      group. However, the fatty change was enhanced in the silymarin group, compared
      with the CCl4 group. The B-mode histogram values were the highest in the
      silymarin group, but the collagen rate was highest in the CCl4-treated group, at
      week 12. These results suggest that the B-mode histogram can be more affected by
      infiltration of lipid than by intact accumulation of collagen fibers. CONCLUSION:
      In the histogram of 8 and 12 weeks, there were significant differences between
      the CCl4-treated group and silymarin group in mean grey levels of B-mode
      ultrasonography. The histogram of B-mode mean grey level has a close correlation
      with fatty change and is useful for the diagnosis of liver fibrosis by
      histopathological analysis.

PMID- 15868944
TI  - Comparison of different protocols for telomere length estimation by combination
      of quantitative fluorescence in situ hybridization (Q-FISH) and flow cytometry in
      human cancer cell lines.
AB  - BACKGROUND: The end of eukaryotic chromosomes terminates with nucleoprotein
      structures called telomeres. They insure several functions including capping the
      end of the chromosomes, ensuring their stability and protecting them from end-to
      end fusion and preventing the activation of the DNA damage checkpoints. MATERIALS
      AND METHODS: A flow-FISH methodology, i.e. quantitative fluorescence in situ
      hybridization (Q-FISH) in combination with flow cytometry, has been developed in
      our laboratory in order to estimate telomere length in three human cancer cell
      lines: K-562 (chronic myelogenous leukaemia), IM-9 (multiple myeloma) and 1301 (T
      cell lymphoblastic leukaemia). Telomeres were visualised after hybridisation with
      FITC-labelled PNA (Peptide Nucleic Acid) probes. We evaluated the most critical
      steps of the flow-FISH protocol to ensure reproducibility. Different
      methodological set ups were compared. Three fixation procedures (ethanol 80%,
      methanol 80% and formaldehyde 4%) were tested besides different fixation times
      (15 min and 60 min) as well as hybridization times (2 h and overnight). For each
      of these protocols the following parameters were compared: forward scatter
      (related to the cell size), side scatter (related to the cell granularity), DNA
      (FL3 and FL4 fluorescence) and PNA content (FL1 fluorescence) using an EPICS XL
      flow cytometer. RESULTS: Regarding the fixation procedures, methanol proved to be
      the best, followed by ethanol and formaldehyde, with respect to the efficiency to
      measure the different parameters cited above. Indeed, fixation using methanol
      gave the optimal PNA signal compared to using ethanol and formaldehyde in two of
      the studied cell lines (K-562 and 1301); the difference observed was highly
      significant in the 1301 cell line. The duration of fixation did not show
      significant interference in the reproducibility of the results for the three cell
      lines studied. An overnight hybridization appeared to be more effective when
      compared to the 2-h hybridization in the case of the K-562 cell line. CONCLUSION:
      The most important steps of the flow-FISH technique, namely the fixative
      procedure, as well as the hybridization and the fixation times, were
      investigated. Considering the latter, suitable protocols were set up for routine
      and fast telomere length estimation in the cancer cell lines.

PMID- 15868945
TI  - Origin of cells cultured in vitro from human breast carcinomas traced by cyclin
      D1 and HER2/neu FISH signal numbers.
AB  - BACKGROUND: We have developed and optimized a feeder layer method for cultivation
      of normal human mammary luminal cells and found it suitable for establishing more
      than 150 primary cultures from individual human breast carcinomas. Here, we
      investigated if the malignant cells that are in situ additionally characterized
      by increased numbers of proto-oncogenes can be traced by the FISH method in the
      ex vivo-derived cultures. MATERIALS AND METHODS: Paraffin sections from 9 tumors
      with derived cell cultures kept frozen in our cell bank were screened by FISH for
      cyclin D1 (CCND1) and c-erb-B2 (HER2/neu) proto-oncogene signal numbers. RESULTS:
      In 6 tumors (5 primary tumors, 1 cutaneous metastasis), increased numbers of FISH
      signals were found in 55-99% of cells. Then, the relevant cell cultures were FISH
      screened; in cell populations maintained for up to 2-6 passages in vitro the
      incidence of cells with increased FISH signals was found to be low (2-16%).
      Moreover, the cells with multiplied signals that survived more than one passage
      in vitro were evidently unable to divide further. However, in all 6 tumors at
      least a small fraction of cells displaying only two signals of CCND1 or HER2/neu
      genes was identified directly in invasive tumor structures in the vicinity of
      cells with multiple signals. CONCLUSION: Our findings suggest that these invasive
      tumor cells displaying only two proto-oncogene signals were most probably
      involved in the initiation and propagation of ex vivo tumor-derived primary cell
      cultures.

PMID- 15868946
TI  - Irradiation dose-response effects on angiogenesis and involvement of nitric
      oxide.
AB  - BACKGROUND: Recent results implicate nitric oxide (NO) in the irradiation-induced
      perturbation of angiogenic mechanisms. We have previously shown, using the chick
      embryo chorioallantoic membrane (CAM) and a dose of 10 Gy, that the NO pathway is
      involved in X-ray-induced anti-angiogenicity. In the current study, we
      investigated the implication of NO in the effects of various doses (2-15 Gy) of
      irradiation on angiogenesis. MATERIALS AND METHODS: X-irradiation, NO synthase
      inhibitors, NO releasing agent and the in vivo CAM angiogenesis model (disc and
      ring method) were used. The CAM areas were irradiated on the 9th or the 14th day
      of embryo development and the vascular density was determined morphologically.
      RESULTS: Doses up to 5 Gy resulted in dose-dependent reduction of vascular
      density, whereas the NO synthase inhibitors, added immediately post-irradiation,
      protected the 9-day CAM from the above anti-angiogenic effects of irradiation. NO
      donor, under certain circumstances potentiated the effects of X-rays when applied
      to the 9-day CAM using the ring method. CONCLUSION: These results confirm the
      implication of NO in the anti-angiogenic mechanism of X-rays and describe the
      dose-response pattern of NO involvement in this action.

PMID- 15868947
TI  - New model for the induction of osteoblastic bone metastases in rat.
AB  - BACKGROUND: We have investigated different models for osteoblastic lesions.
      Currently, there are two models using MatLyLu R-3327prostate cancer cells: tumor
      cell application in the left heart ventricle and intravenous application with
      concomitant transient surgical clamping of the lower caval vein. MATERIALS AND
      METHODS: Thirty male Copenhagen rats (age 9+/-2 months, mean weight 323+/-21 g)
      were each injected with 200,000 R-3327 prostate cancer cells. In 10 rats the left
      ventricle route was used (group 1), in an other 10 rats the intravenous route
      (group 2), while in the third group of 10 rats a new model of a direct intra
      osseous route was applied (group 3). Additionally, a control group of 5 rats
      underwent the same procedure as in group 3, but only saline without tumor cells
      was administered. A 99mTc-HMDP bone scan and histological examination of bone and
      lung were performed for follow-up. RESULTS: In the bone scan, bone lesions could
      be not visualized in groups 1 and 2, but in group 3 osteoblastic lesions were
      observed in both femora in 9 out of 10 rats. Upon histological examination, there
      were lung metastases in animals from groups 1 and 2, but not in group 3. Clinical
      signs for bone metastases in the lumbar spine (motor disablement of the hind
      legs) were found in groups 1 and 2. CONCLUSION: The intra-osseous administration
      of MatLyLu R-3327 prostate cancer cells represents a useful and effective model
      for osteoblastic bone lesion, and allows further autoradiographic evaluation of
      bone uptake using bone-seeking radiopharmaceuticals.

PMID- 15868948
TI  - The JNK interacting protein JIP-1 and insulin like growth factor II genes are co
      expressed in human embryonic tumours.
AB  - JNK interacting protein 1 (JIP-1) is a pivotal scaffolding protein in the JNK
      signalling pathway. It is believed to play a role in the mediation of mitogenic
      messages from the plasma membrane to the cell interior. Recent evidence suggests
      that the JIP-1 gene is co-regulated with the insulin like growth factor II (IGF
      II) gene, thereby contributing to the growth-promoting effects of this potent
      growth factor. In this study, fourteen embryonic tumours were examined for the
      expression of JIP-1 and IGF II. It was found that, irrespective of histological
      type and expression level, the two genes showed a high degree of co-variation in
      the sense that high IGF II expression was followed by high expression of JIP-1.
      This finding further supports the notion that JIP-1 and IGF II act in concert to
      enhance cell proliferation.

PMID- 15868949
TI  - Presence and incidence of DNA sequences of human polyomaviruses BKV and JCV in
      colorectal tumor tissues.
AB  - The human polyomaviruses JCV and BKV are widespread within population, as shown
      by serological studies. However, exposure to these viruses does not seem to have
      pathological consequences in immunocompetent individuals, while in
      immunocompromised or immunosuppressed patients, polyomaviruses can be activated,
      giving rise to serious pathologies. Viral DNA sequences were also found in cells
      from a number of human tumors of mesothelial origin, suggesting that activation
      of BKV and JCV, taking place in genetically predisposed and/or in immunodepressed
      individuals, might be involved in the mechanisms of tumor transformation. In this
      study, samples obtained from 18 patients with colon rectal carcinoma were probed
      for the presence of JCV and BKV by three different techniques: Southern blot, PCR
      and in situ hybridization. Our results demonstrate that viral DNA sequences were
      present in 16 out of the 18 cases considered (88.9%). In the large majority of
      cases, viruses were detected both in the tumor mass and in the surrounding
      healthy tissues. Lymphocytes in the investigated areas were also found to be
      infected by polyomaviruses. These data indicate, for the first time, a possible
      involvement of polyomaviruses in the pathogenesis of tumors of endothelial
      origin, like the human colon rectal carcinoma.

PMID- 15868950
TI  - Tumour therapy with genes encoding apoptin and E4orf4.
AB  - The aim of our study was to investigate whether apoptin and e4orf4 pro-apoptotic
      genes, transferred by means of electroporation, were suitable for gene therapy of
      tumours. The two genes were chosen for our study because the proteins they encode
      induce apoptosis in transformed cells only. The apoptin gene was synthesised
      based on a published nucleotide sequence. MTT and TUNEL tests confirmed that both
      the synthesised apoptin gene and the e4orf4 gene indeed induced apoptosis in COS
      7, Renca and B16(F10) cell lines. Therapeutic DNA was then administered via
      electroporation directly into murine B16(F10) tumours. Distinct tumour growth
      inhibition was seen only during the treatment. The cessation of therapy caused
      tumour re-growth. Obviously, the efficiency of gene transfer using
      electroporation is low and did not induce a permanent therapeutic effect.

PMID- 15868951
TI  - Efficacy of two commercial preparations of interferon-alpha on human
      papillomavirus replication.
AB  - Previous studies on the effectiveness of interferon (IFN) therapy in the
      treatment of cervical carcinoma have produced highly inconsistent results and the
      conclusion regarding the efficacy of IFNs has been quite controversial. As the
      organotypic raft culture system mimics the differentiation-dependent life cycle
      of human papillomavirus (HPV), the causative agent of cervical cancer, we
      utilized the raft culture system to study the effects of interferon-alpha (IFN
      alpha) on the vegetative replication of HPV. The effect of different
      concentrations of Interferon-alpha-n3 (Alferon N) and Interferon-alpha-2b (Intron
      A) on HPV16, HPV18 and HPV31b vegetative replication was studied in cell lines
      harboring episomal copies of these high risk HPV types. Our studies indicate that
      Alferon N and Intron A varied in a concentration-dependent manner in their
      ability to affect the viral load of different HPV types. Treatment with an
      increasing concentration of IFN-alpha preparations did not always correlate with
      a stepwise inhibition of HPV replication.

PMID- 15868952
TI  - Anatomical distribution of small cell lung cancer: effects of lobe and gender on
      brain metastasis and survival.
AB  - BACKGROUND: Primary small cell lung cancer (SCLC) has a predilection for the
      right rather than the left lung. The aim of this study was to examine the
      association between gender and pulmonary location and to examine the effects of
      these variables on the incidence of brain metastasis and the survival rate of
      patients with SCLC. MATERIALS AND METHODS: We conducted a retrospective review of
      medical charts of patients diagnosed with SCLC between January 1989 and December
      2002 at MeritCare Hospital in Fargo, ND, USA. The effects of the anatomical site
      of SCLC, age, gender, body mass index, stage of SCLC and treatment of SCLC on the
      incidence of brain metastasis and survival were examined using univariate and
      multivariable Cox proportional-hazards regression models. RESULTS: Two-hundred
      and thirty patients were identified with SCLC. One hundred and forty-eight (64%)
      were male and 82 (36%) were female. SCLC was significantly more common in the
      right upper lobe for females (51%) than for males (32%) (p-value=0.005) and in
      the left upper lobe for males (28%) compared to females (11%) (p-value=0.003).
      Survival was significantly longer in both younger patients (48 weeks vs. 26
      weeks; log-rank p-value=0.03) and female patients (50 weeks vs. 36 weeks; log
      rank p-value=0.01). The multivariable Cox model showed an adjusted HR of 1.52
      (95% confidence interval 1.01-2.3) for the right lung relative to the left lung.
      We found no impact of anatomical distribution or pulmonary location on the
      incidence of brain metastasis. CONCLUSION: In these data, SCLC is more common in
      the right upper lobe for females. Right lung and male gender are associated with
      a worse prognosis, which may suggest that more aggressive therapy is needed in
      these patients.

PMID- 15868954
TI  - Adhesion molecule CD44 as a prognostic factor in laryngeal cancer.
AB  - BACKGROUND: Loss of expression of CD44 has been shown to be a factor of poor
      prognosis in some types of tumors. The purpose of this study was to analyze this
      event in relation to the survival of patients with laryngeal cancer. PATIENTS AND
      METHODS: The expression of adhesion molecule CD44 was studied in 137 patients
      with laryngeal cancer. Data were gathered on clinical (primary tumor location,
      pyriform sinus involvement and tongue base damage) and pathologic (T, N,
      differentiation, inflammatory response, tumor thickness, surgical margin
      involvement, and CD44 expression) parameters. Immunohistochemical studies were
      carried out using DF1485 anti-CD44 monoclonal antibody. RESULTS: In 29 tumors
      (21.1%) < 25%, in 18 (13.1%) 25%-49%, in 42 (30.6%) 50%-74%, and in 48 (35.0%) >
      or = 75% of the neoplastic cells expressed CD44. A Cox proportional risks
      multivariate analysis identified CD44 expression and surgical margin involvement
      as the parameters most associated with survival (p<0.001). CONCLUSION: The
      reduced expression of CD44 behaves as a marker of a poor laryngeal cancer
      prognosis.

PMID- 15868953
TI  - Inhibition of angiogenic activity of renal carcinoma by an antisense
      oligonucleotide targeting fibroblast growth factor-2.
AB  - BACKGROUND: Fibroblast growth factor-2 (FGF-2) induces angiogenesis, critical for
      the growth and metastatic spread of tumors. MATERIALS AND METHODS: The effect of
      blocking FGF-2 synthesis by an antisense phosphorothioate oligodeoxynucleotide
      (PS-ODN2) was evaluated on the angiogenic activity of Caki-1 and of a cell line
      isolated from a renal carcinoma bone metastasis (CRBM-1990). After the
      transfection with PS-ODN2, FGF-2 mRNA, protein expression and angiogenic activity
      were evaluated. RESULTS: In Caki-1, a not significant decrease in the released
      FGF-2 was observed after 72 hours. In CRBM-1990, a not significant decrease in
      intracellular FGF-2 protein was observed after 72 hours. Endothelial cell
      migration induced by the conditioned media from Caki-1 treated with PS-ODN2 for
      72 hours was significantly reduced. CONCLUSION: PS-ODN2 treatment of the
      established line Caki-1 induced minimal variations in FGF-2 expression, but
      inhibited endothelial cell migration. In CRBM-1990 cells, PS-ODN2 determined a
      decrease in intracellular protein without reducing the ability to induce
      endothelial cell migration and proliferation.

PMID- 15868955
TI  - The expression of p21/WAF-1 and cyclin B1 mediate mitotic delay in x-irradiated
      fibroblasts.
AB  - BACKGROUND: To better understand the relationship between mitotic delay and the
      disruption of cyclin B1 and p21 in x-irradiated fibroblasts, studies were carried
      out to establish correlations between the downregulation of cyclin B1 by the
      cyclin kinase inhibitor (CKI) p21 and the induction of mitotic delay in the
      NIH3T3 fibroblast. MATERIALS AND METHODS: Cell cycle kinetics were used to
      analyze mitotic delay in irradiated NIH3T3 cells and immunocytochemistry
      incorporated to assess the expression of cyclin B1 and p21, following 2 or 4 Gy x
      irradiation. RESULTS AND DISCUSSION: Results indicate a dose dependent increase
      in mitotic delay accompanied by a downregulation of cyclin B1 and corresponding
      upregulation of the CKI p21 in exponentially growing cultures. Data indicates
      that the induction of radiation-induced division delay appears to be dependent on
      the p21 inhibition of cyclin B1 and, furthermore, p21 and cyclin B1 expression
      are highly dependent on cell density.

PMID- 15868956
TI  - MCI-186 inhibits tumor growth through suppression of EGFR phosphorylation and
      cell cycle arrest.
AB  - BACKGROUND: It has been suggested that radicals stimulate tumor cell growth. We
      examined if the hydroxyl radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one
      (MCI-186), affects tumor growth in vitro. MATERIALS AND METHODS: Human
      hepatocarcinoma HepG2, mesothelioma MSTO-211H, gastric carcinoma TMK-1 and breast
      carcinoma MCF-7 were used for cell proliferation assay. Cell cycle analysis was
      performed using propidium iodide for fluorescence activated cell sorter. By
      Western blotting, EGF receptor (EGFR) phosphorylation and EGFR expression were
      analyzed. RESULTS: Growth inhibition was observed from 10 microM to 300 microM of
      MCI-186 in a dose-dependent manner. Cell cycle analysis revealed that MCI-186
      arrested the cell cycle at the G0/G1-phase. MCI-186 inhibited EGF-stimulated cell
      growth. The phosphorylation level of EGFR was decreased by MCI-186, but the EGFR
      level was unchanged. CONCLUSION: From the data obtained, we suggest that tumor
      inhibition by MCI-186 was due, at least in part, to the modulation of EGFR
      signaling and cell cycle arrest.

PMID- 15868957
TI  - Structure-activity relationships of a new class of aromatic bisphosphonates that
      inhibit tumor cell proliferation in vitro.
AB  - We previously reported a simple and efficient one-pot procedure for synthesis of
      1-hydroxymethylene-1,1-bisphosphonic acids (HMBP). According to this method, we
      synthesized a series of new aromatic HMBP and investigated structure-activity
      relationships by evaluating their anti-proliferative activity against A431 human
      tumor cell line. Our results showed that the introduction of an extra methylene
      group in a pyridyl-containing R2 side chain increased 100-fold the anti
      proliferative activity of the HMBP. In contrast, this chemical modification did
      not modify the anti-proliferative activity of compounds substituted with a phenyl
      containing R2 side chain. Para-substitution of the phenyl ring with various
      groups markedly influenced the HMBP activity, the order of potency (bromine >
      chlorine > fluorine = none) closely matching the atomic volume of the substituted
      group. Moreover, changes in the substitution position of the bromine group also
      affected the anti-proliferative activity, the more potent activity being obtained
      with para-substitution of the phenyl ring. In conclusion, this structure-activity
      study led us to identify the new aromatic HMBP [(4-Bromo-phenyl)-hydroxy
      phosphono-methyl]-phosphonic acid as a potent in vitro anti-proliferative
      molecule against tumor cell lines (IC50 value of 9.5 x 10(-5) M). Interestingly,
      this compound can be further easily esterified on its phosphonic acid functions
      according to our chemical method and, thus, represents a potential candidate for
      the development of new esterified HMBP with enhanced pharmacokinetics.

PMID- 15868958
TI  - Resistance mechanisms following cisplatin and oxaliplatin treatment of the human
      teratocarcinoma cell line 2102EP.
AB  - BACKGROUND: Oxaliplatin and cisplatin are widely used in cancer chemotherapy,
      however, their clinical efficiency is often limited by the development of
      resistance. MATERIALS AND METHODS: We examined different mechanisms of resistance
      in the human teratocarcinoma cell line 2102EP following exposure to cisplatin or
      oxaliplatin. Cells were exposed ten times with IC90-doses of 30 microM cisplatin
      and 50 microM oxaliplatin, respectively. Different cell clones were tested for
      expression of resistance using the SRB-assay. Moreover, resistance mechanisms in
      terms of drug uptake, platinum-adduct formation, GSH metabolism, DNA mismatch
      repair and p53 protein function were investigated. RESULTS: Three cisplatin cell
      clones with significant resistance factors of 2.0 to 2.6 were found. Two
      oxaliplatin cell clones showed only weak resistance, with resistance factors of
      1.6 and 1.7, respectively. In all three cisplatin-exposed cell clones a decreased
      cellular uptake of cisplatin was found. Furthermore, mechanisms of DNA damage
      tolerance may also play a role in the development of cisplatin-resistance in
      these cells. However, only two cell clones showed a decreased level of platinum
      DNA-adducts. An increased DNA-repair of platinum-DNA adducts was not seen. In
      addition, no differences in expression of mismatch-repair proteins MSH2 and MLH1,
      tumor suppressor protein p53, or glutathione metabolism were found. However,
      significant resistance mechanisms for the observed oxaliplatin resistance could
      not be identified, although in one oxaliplatin-exposed cell clone, there was some
      evidence that a decreased cellular uptake of oxaliplatin may contribute to the
      observed low level resistance. CONCLUSIONS: The data add weight to the hypothesis
      that resistance mechanisms following oxaliplatin exposure may be similar to
      cisplatin. The precise mechanisms of resistance in the oxaliplatin-resistant cell
      clones are still not fully understood and current studies are underway to further
      eluciate this finding.

PMID- 15868959
TI  - Proenzyme therapy of cancer.
AB  - Proteases and their inhibitors have long been investigated in numerous tumor
      systems, and at the tumor growing front, their balance has been universally found
      to be shifted towards higher proteolytic activities. However, out of many
      promising serine and metalloproteinase inhibitors, none are included in cancer
      treatment regimens at present. The current search for active antiproteolytic
      compounds is in contrast to the classical approach developed by John Beard, who
      suggested treating advanced cancer by fresh pancreatic extracts whose antitumor
      activity was based on their proteolytic potential. We followed John Beard's
      recommendations by using purified pancreatic proenzymes/enzymes,
      trypsinogen/trypsin (TG/TR), chymotrypsinogen/chymotrypsin (CG/CH) and amylase
      (AM). The mixture of these enzymatic activities produces potent antimetastatic
      and antitumor effects in cellular, animal and human systems. The treatment of
      cultured tumor cells with TR and CH at nanomolar [corrected] concentrations,
      comparable to those achieved in the blood of the patients, causes complete arrest
      of the directional movement of metastatic cells. Conversely, the same treatment
      of normal cells results in enhanced motility and an accelerated closure of the
      gap created in cell monolayers. Further, treatment of cells with serine proteases
      results in the formation of cellular 3-dimensional structures such as lamellae,
      cell streams and aggregates. In some cell types, the aggregates are compacted via
      cadherin-based cell-cell communication systems and form compact spheroids. In the
      highly metastatic cells with lower cadherin expression, the ability to form
      spheroids also diminishes. Tumor cells unable to form spheroids when treated with
      proteases are subject to elimination by apoptosis. In contrast, a large
      proportion of cells that form spheroids remain viable, although they are
      metabolically suppressed. Protease-treated tumor cells contain a disrupted actin
      cytoskeleton and exhibit a loss of front-to-back polarity. We hypothesize that
      the provision of zymogens, rather than the enzymes, was of crucial importance to
      the clinical effectiveness in the human trials conducted by Beard and his co
      workers. The precursor nature of the active enzymes may offer protection against
      numerous serpins present in the tissues and blood. Experimental evidence supports
      the assertion that the conversion from proenzyme to enzyme occurs selectively on
      the surface of the tumor cells, but not on normal cells. We believe that this
      selectivity of activation is responsible for the antitumor/antimetastatic effect
      of proenzyme therapy and low toxicity to normal cells or tumor host. Elevated
      levels of endostatin and angiostatin appear in the blood of TG/CG/AM-treated
      tumor-bearing mice, but not in tumor mice treated with the vehicle alone or in
      proenzyme-treated tumor-free mice. These findings support the conclusion that
      proteolysis is the active mechanism of the proenzyme treatment. Future studies
      will focus on the molecular mechanisms of the proenzyme therapy including the
      identification of molecular target(s) on the tumor cells. In conclusion, we have
      discovered that proenzyme therapy, mandated first by John Beard nearly one
      hundred years ago, shows remarkable selective effects that result in growth
      inhibition of tumor cells with metastatic potential.

PMID- 15868960
TI  - Mono- or di-fluorinated analogues of flavone-8-acetic acid: synthesis and in
      vitro biological activity.
AB  - BACKGROUND: Previously, the antitumour activity of some flavone-8-acetic acid
      (FAA) derivatives substituted with an acid function in position 2 of the benzene
      ring was evaluated. The most active compound resulted the one bearing a fluorine
      atom in position 7 of the flavone nucleus. In this paper, we evaluated new mono-
      or di-fluorinated FAA derivatives. MATERIALS AND METHODS: The cytotoxicity
      towards two human ovarian adenocarcinoma cell lines, the capability to stimulate
      human mononuclear cells and murine macrophages' lytic properties were evaluated
      by MTT. Moreover, the potentiation of lipopolysaccharide (LPS) activity was
      studied by ELISA analysis of TNF-alpha release. RESULTS: The analogues showed a
      direct cytotoxicity comparable to that of 5,6-dimethyl-xanthen-9-one-4-acetic
      acid (DMXAA), at present in clinical trials. None of the tested compounds was
      able to stimulate human mononuclear cells' lytic properties after either 4- or 24
      h treatment, while after 4-h treatment, the derivative 5a was more able to
      stimulate murine macrophages with respect to DMXAA. Moreover, a significant
      increase of 5c and 5d activation was obtained with LPS association, reflected by
      TNF-alpha production as well. CONCLUSION: Like FAA, the new fluorinated
      derivatives 5a, 5c and 5d showed remarkable activity in murine cells, but this
      was not confirmed in human models.

PMID- 15868961
TI  - Quantitative and functional assay of MDR1/P170-mediated MDR in ascites cells of
      patients with ovarian cancer.
AB  - BACKGROUND: MDR1-associated P-glycoprotein-dependent multidrug resistance is a
      common cause of chemotherapy failure in patients with advanced ovarian cancer.
      Here, we describe a clinical method for simultaneously assessing the expression
      and function of the MDR1/Pgp in tumour cells from ascites of patients with
      malignant ovarian carcinoma. MATERIALS AND METHODS: Cells from ascites from 35
      patients were collected. The expression and function of Pgp were detected by flow
      cytometry. For functional study, rhodamine 123 was used. RESULTS: Using the Pgp
      specific UIC2 and MM6.15 antibodies, we demonstrated the presence of Pgp in 10
      79% (38.9+/-20, 7; n=35) of the CA 125-positive cell subpopulations. The results
      of the functional assay showed strong correlation with the level of Pgp
      expression (r=0.976; p=3.2x10(-5)). CONCLUSION: Direct detection of the
      expression level and function of MDR1/Pgp in the ascites provide useful
      information for the more efficient treatment of malignant diseases by proper
      adjustment of the chemotherapeutic protocol.

PMID- 15868962
TI  - Perinatal mortality in Kenya: time for action.

PMID- 15868963
TI  - Perinatal mortality in the Special Care Nursery of Moi Teaching and Referral
      Hospital, Eldoret, Kenya.
AB  - OBJECTIVES: To determine the mortality rate and causes of death of all infants
      admitted to the Special Care Nursery (SCN) of a tertiary referral hospital in
      rural Kenya. DESIGN: Prospective and Cross-sectional study SETTING: Special Care
      Nursery, Moi Teaching and Referral Hospital, Eldoret, Kenya. SUBJECTS: All
      infants admitted to the Special Care Nursing (SCN). MAIN OUTCOME MEASURES:
      Survival status at seven postnatal days; major causes of mortality and morbidity.
      RESULTS: Three hundred and thirty five babies were studied between February and
      September 1999. Out of these 167 (49.9%) were male. There were 50 (15%) preterm
      and 124 (37.3%) low birth weight babies. There were 198 (76.2%) appropriate for
      gestational age (AGA), 46 (17.7%) small for gestational age and 16 (6.2%) large
      for gestational age babies. The seven day mortality rate of infants admitted to
      the Special Care Nursery was 66 (19.7%). Birth asphyxia and respiratory distress
      accounted for most deaths. Infants who were admitted primarily because the mother
      remained under general anesthesia generally did well. Logistic factors, including
      inadequate training for neonatal resuscitation in ward cadre of staff,
      unavailability of trained paediatricians and obstetricians, and inadequate
      operating theatre supplies were all found to delay treatment and likely to
      increase mortality. CONCLUSION: Morbidity and mortality of infants born at the
      MTRH remain high. The most common cause of mortality remains birth asphyxia. Some
      causative factors, such as lack of resources or personnel, are logistic and could
      be rectified. Antenatal care had a significant positive impact on both morbidity
      and mortality.

PMID- 15868964
TI  - Stool viruses among paediatric patients from a Nairobi clinic, Kenya.
AB  - OBJECTIVE: To document the clinical presentation and prevalence of stool viruses
      among children presenting with symptoms of acute gastroenteritis (AGE) at
      Gertrude's Garden Children's Hospital, Nairobi, Kenya. DESIGN: Retrospective case
      control study. SETTING: A private paediatric clinic in Nairobi. RESULTS: Viral
      antigen was detectable in the stool samples of 21 (rotavirus alone in ten cases,
      adenovirus alone in seven cases, and both viruses in four cases). Diarrhoea was
      almost universally present (20/21 cases) and was reported more frequently than in
      a control group of ten children with clinical acute gastroenteritis whose stools
      tested negative for viruses. Fever, an elevated total leukocyte count, and
      neutrophilia were commonly observed in patients with viral gastroenteritis. Eight
      children with viral AGE were treated with antibiotics and eight children were
      admitted to hospital. CONCLUSION: A viral etiology can frequently be identified
      among children in Nairobi with AGE. Fever, an elevated leukocyte count, and
      neutrophilia were not helpful in differentiating viral from non-viral AGE in this
      series. Supportive management consisting of outpatient oral rehydration therapy
      without antibiotic treatment should be considered in the non-toxic child with
      AGE.

PMID- 15868965
TI  - Anaesthesia for neonatal surgical emergencies in a semi-urban hospital, Nigeria.
AB  - OBJECTIVE: To establish the techniques of anaesthesia for neonatal surgical
      emergencies in a semi-urban hospital in Nigeria, assess their adequacy and make
      recommendations to improve our practice. DESIGN: Retrospective study. SETTING:
      Obafemi Awolowo University Teaching Hospital, Ile-lfe, Nigeria, from January 1990
      to December 2000. SUBJECTS: One hundred neonates aged one to twenty eighty days.
      RESULTS: One hundred neonatal surgical emergencies were operated but only 76 case
      notes were available for review. Three hundred and fifty eight elective neonatal
      surgeries were done during the same period. The ASA classification were: ASA
      IE=10, 2E=25, 3E=28, 4E =12 and 5E=1. The mean weight was 2.66+/ 0.52 kg. Over
      95% of the cases were done under general anaesthesia. Anorectal malformations and
      intestinal obstruction were the most common indications for surgery (64.5%).
      Nurse anaesthetists gave over 50% of the anaesthetics. Peri-operative adverse
      events such as tachycardia, respiratory distress, aspiration and hypothermia were
      recorded in 11.8% of the cases. Mortality was 39.2%. CONCLUSION: General
      anaesthesia is still the main technique of anaesthesia and mortality following
      surgery is still high. Efforts should be made to train appropriate personnel to
      provide improved care and thereby reduce morbidity and mortality.

PMID- 15868966
TI  - Occurrence of contralateral inguinal hernia in children following unilateral
      inguinal herniotomy.
AB  - OBJECTIVE: To review the occurrence of contralateral inguinal hernia in infants
      and children who presented with unilateral inguinal hernia and underwent
      herniotomy in order to establish whether simultaneous contralateral exploration
      is a necessity in our environment. DESIGN: A retrospective study. SETTING:
      Muhimbili National Hospital Paediatric surgical ward. SUBJECTS: Seven hundred and
      thirty two children. RESULTS: Twenty five infants and children developed an
      inguinal hernia on the contralateral side 2-76 months after herniotomy. Follow-up
      period was one to thirteen years. Six hundred and seventy one were boys and sixty
      one girls (M:F = 11:1). Right side presentation was seen in two-thirds of the
      children. Subsequent contralateral hernia occurrence was more common in girls
      (4.9%) and slightly higher in children above 12 months of age (3.5%) but these
      comparisons were not significant (p values were 0.45 and 0.89 and R.R. values
      were 0.97 and 0.67 respectively). Subsequent development of contra lateral hernia
      in children with left-sided hernia was high (6.7%) and this was statistically
      significant (p = 0.002, R.R. = 3.38). CONCLUSION: The risk of occurrence of
      contra-lateral inguinal hernia following unilateral inguinal herniotomy is not
      significantly excessive when compared by age or sex implying that routine
      exploration on the contralateral side in infants and children clinically
      presenting with unilateral inguinal hernia is not justified and we recommend
      herniotomy only when there is adequate clinical evidence of an inguinal hernia.
      Despite the significant risk of developing a contralateral hernia in children
      with left-sided hernia, the authors do not recommend routine right-sided
      exploration as the frequency is not high.

PMID- 15868967
TI  - Socio-demographic characteristics and clinical features among patients attending
      a private paediatric dental clinic in Nairobi, Kenya.
AB  - OBJECTIVES: To evaluate the socio-demographic characteristics, chief complaints
      and clinical presentation of children attending a private dental clinic in
      Nairobi, Kenya. DESIGN: A retrospective survey of dental clinic records. SETTING:
      A private dental clinic in Nairobi, Kenya. SUBJECTS: All patients aged 0-18 years
      who were first-time attenders at the dental clinic during a three year period.
      RESULTS: The records of 800 patients were examined, comprising 395 males and 405
      female children. The average age was 7.2 years (95%CI, 6.9-7.4). Referral to the
      clinic for treatment was mostly by self (81.4%). Most patients (57.9%) were self
      sponsored for their dental treatment. Majority of the patients attending (86.8%)
      did not clinically have any underlying medical conditions. The major complaints
      for most patients were dental decay (27.4%) and dental pain (21.6%). Very few
      children (7.6%) attended for dental check-up. Five hundred and forty nine (68.6%)
      of the children suffered from dental decay while 294 (36.8%) suffered from
      gingivitis. The average number of teeth decayed was 4.02, SD +/- 2.4 (95% CI 3.8
      4.2). Most carious lesions occurred in the younger children. There was a
      significant increase in the occurrence of decay over the three year period of the
      study. Significantly higher levels of gingivitis was observed in the prepubertal
      and pubertal age group. Attendance for traumatic injuries was relatively low with
      only 46 (5.8%) children reporting traumatic injuries to their dentitions. Most
      traumatic injuries involved the anterior teeth as a result of falls. Treatment
      given at the first visit was mainly restorative (28.6%) followed by dental
      extractions (25.4%). CONCLUSION: The average are of patients attending the clinic
      was 7.2 years. Interdisciplinary referral was low since most patients were self
      referred and self sponsored for treatment. Dental caries was prevalent,
      necessitating a high demand for restorative treatment. Although gingivitis was
      less prevalent, it was significant among children in the prepubertal years.

PMID- 15868968
TI  - Malaria and intestinal helminthiasis in school children of Kumba Urban Area,
      Cameroon.
AB  - BACKGROUND: Malaria and intestinal helminthiasis are parasitic diseases causing
      high morbidity and mortality in most tropical parts of the world, where climatic
      conditions and sanitation practices favour their prevalence. These infections do
      co-exist and have different effects on infected individuals. OBJECTIVES: To
      assess the level of endemicity of malaria and helminth infections in school
      children of the Kumba Urban Area of Cameroon, and to determine how these
      infections relate to each other. DESIGN: Cross sectional study. SETTING: Four
      primary schools in the Kumba urban area. SUBJECTS: Two hundred and forty three
      randomly selected pupils aged four and fifteen years of both sexes. RESULTS: All
      two hundred and forty three pupils had malaria parasites in their blood. The
      geometric mean parasite load was 1282 parasites per microl of blood. Only 17
      pupils were anaemic (PCV<30%), The helminth infections showed a 38.3% prevalence,
      with a geometric mean parasite load of 687 eggs per gram of faeces. Co-infections
      were recorded in 38.3% of the pupils. There was no significant correlation
      between the helminth and malaria parasite densities (r=0.04, P=0.7337).
      CONCLUSION: Both malaria and helminth parasites do co-exist without clinical
      symptoms of infection in school children of the Kumbi Urban Area.

PMID- 15868969
TI  - Congenital syphilis in a Nairobi maternity hospital.
AB  - OBJECTIVE: To assess adverse pregnancy outcome associated with maternal syphilis
      and congenital syphilis rate based on FTA-ABS-19s-IgM. DESIGN: Descriptive cross
      sectional study. SETTING: Pumwani Maternity Hospital (PMH), the largest maternity
      unit in Nairobi, Kenya. SUBJECTS: Rapid Plasma Reagin reactive women and their
      live born infants. MAIN OUTCOME MEASURES: Syphilis serology in pregnant women,
      FTA-ABS-19s-IgM in cord blood and pregnancy outcome. RESULTS: Three hundred and
      seventy seven out of 12,414 women (3%) were RPR+. 4.0% of RPR+ and 1.4% of RPR-
      women delivered a stillbirth (OR 3.0, p<0.001). 19% of RPR+ and 10% of RPR- had
      low birth weight deliveries (OR 2.1, p<0.001). Mothers untreated for syphilis
      during pregnancy had significantly more preterm births (18.5% vs 9.2%, OR 2.3,
      p=0.026), and more stillbirths (5.4% vs 1.0%, OR 6.3, p=0.044). Of the 200
      randomly selected cord bloods of RPR+ women, 142 (72%) were TPHA+. Nine (6.3%) of
      the 142 TPHA+ cords were FTA-ABS-19s-IgM+. CONCLUSIONS: Stillbirth and low birth
      weight rates were high in RPR+ untreated pregnant women and treatment
      significantly improved pregnancy outcome. Based on very stringent laboratory
      criteria (FTA-ABS-19s-IgM), 6.3% of live born infants with TPHA+ cord blood were
      considered syphilis infected.

PMID- 15868970
TI  - Alcohol abuse among patients with and without HIV infection attending public
      clinics in western Kenya.
AB  - OBJECTIVE: To evaluate the prevalence of hazardous drinking among persons with
      and without HIV/AIDS attending both urban/hospital-based and rural clinics in
      western Kenya. DESIGN: Cross sectional survey. SETTING: The Moi Teaching and
      Referral Hospital and the Mosoriot rural health care Centre. SUBJECTS: Two
      hundred and ninety nine adults with and without HIV/AIDS at a teaching and
      referral hospital and rural health centre. MAIN OUTCOME MEASURES: Results of the
      World Health Organization's Alcohol Use Disorders Identification Test (AUDIT)
      where a score of > 8 is indicative of hazardous alcohol consumption. Independent
      correlates of hazardous drinking were identified using logistic regression
      analysis including adjustment for common covariables. RESULTS: Study participants
      were relatively young (38 +/- 9 years) with 55% being male and 54% completing the
      AUDIT in Kiswahili. Home-made alcohol was more commonly drunk by patients
      attending the rural health centre while commercial beer was more commonly drunk
      by patients attending the teaching and referral hospital clinics. Approximately
      half (54%) of participants reported hazardous drinking behaviour (AUDIT score=9.9
      +/- 9.4). Hazardous drinking was most prevalent among men attending the rural
      health centre (83% hazardous drinkers, AUDIT score=16.0 +/- 9.1). In
      multivariable analyses adjusting for age, sex and site of care, men remained more
      than nine times (odds ratio=9.3, 95% C.I.=5.1-16.9) likely to report hazardous
      drinking behaviour compared to women. CONCLUSIONS: Hazardous drinking is common
      among patients with and without HIV/ AIDS in western Kenya and is dramatically
      more common among rural men than women. Effective interventions for HIV/AIDS in
      this setting must include a concetrated effort to reduce hazardous drinking.

PMID- 15868971
TI  - Simulation model for dental arch shapes.
AB  - OBJECTIVE: To develop a simulation model for dental arch shapes. DESIGN: Analysis
      of measurements of dental casts to determine a general second degree equation for
      the dental arches. SETTING: Department of Human Anatomy and School of Computing
      and Informatics, University of Nairobi. SUBJECTS: The measurement of dental
      casts, 30 (15M and 15F) each from three Kenyan ethnic groups (Maasai, Kalenjin,
      Kikuyu), aged 12 years. RESULTS: The arches change their shapes from a parabola
      to an ellipse, governed by the boundary conditions at the position of the canine
      tooth, based on the general second degree equation for the conic sections.
      CONCLUSION: The simulation model graphically confirms the change from parabolic
      to elliptic shapes of dental arches with boundary conditions at the canine. This
      could be used to show the changes in dental arches for other ethnic groups.

PMID- 15868972
TI  - Use of educational workshop to promote mobility during childbirth.
AB  - OBJECTIVE: To evaluate the impact of an educational intervention to introduce the
      principles of evidence based obstetric care and encourage mobility during labour
      in government hospitals in Dar es Salaam. DESIGN: An observational study.
      SETTING: Four government hospitals; two in Dar es Salaam and two in coastal
      region of Tanzania. RESULTS: Following implementation of the workshops, practice
      changed significantly for mobility during labour at the district and regional
      hospitals; midwives at these hospitals appeared to be aware of the benefits and
      were willing to encourage women to be mobile during labour. Practice changed
      little at the referral hospital. Most women delivering at the referral hospital
      had been transferred from regional or district hospitals with complications.
      CONCLUSION: This small study demonstrates the potential of using educational
      workshops to change childbirth practice at the district and regional level in
      Tanzania. Institutionalisation of practice changes involves influencing policy
      makers, engaging opinion leaders to disseminate evidence and advocacy for change
      among their peers, as well as developing mechanisms to overcome barriers to
      practice change at the hospital level. Results from this study will feed in to a
      project to develop evidence-based guidelines for childbirth care, involving
      policy makers, practitioners and hospital managers.

PMID- 15868973
TI  - Psychological manifestations and heart disease.

PMID- 15868974
TI  - Coronary artery disease and symptoms of depression in a Kenyan population.
AB  - BACKGROUND: Depression and heart disease are replacing the traditional enemies of
      Africa such as infectious diseases and malnutrition as the increasing causes of
      disability and premature death. Little is known about the co-morbidity of heart
      disease and depression in Africa. OBJECTIVE: To describe the prevalence of
      depression in Black Africans with and without Coronary Artery Disease as
      documented on coronary angiography at the Nairobi Hospital. DESIGN: Prospective
      comparative study. SETTING: A private not for Profit 210 bed hospital, catering
      for fee paying middles class clintele. RESULTS: Of the eighteen patients with an
      abnormal angiogram, the highest score on the BDI was 9 while the average was
      2.11. Of the seven with normal angiograms, the highest BDI was 5, and the average
      was 1.71. There was no statistical significance in these differences. CONCLUSION:
      While African scientists must continue to concentrate on the urgent medical
      priorities of today (AIDS, malaria, measles, etc), cognisance has to be made of
      the other emerging epidemic, of the co-morbidity of coronary artery disease and
      depression. That no significant difference in depression score between the two
      groups was found could be due to a number of reasons including the small sample
      size achieved in this first study of its kind in Kenya.

PMID- 15868975
TI  - Postpartum depression in a maternity hospital in Nigeria.
AB  - OBJECTIVE: To explore the recognition and management of postpartum depression
      (PPD) by the obstetric team in a maternity hospital concomitantly, was to find
      the rate of PPD in the centre. DESIGN: A descriptive cross-sectional study.
      SETTING: Island Maternity Hospital, Lagos, Nigeria; a moderately large obstetric
      facility with 68 beds and 42 paediatric cots. SUBJECTS: The medical staff
      including doctors and nurse midwives in the study centre. Concomitantly, a sample
      of women that delivered in the hospital during the study period. RESULTS: Seventy
      two (65.5%) of the total 110 obstetric staff in the hospital consented to the
      study; made up of 10 doctors and 62 midwives of varying cadres. 43.1% of them
      admitted their difficulty to recognise PPD with X2 of 25.8, while 19.4% expressed
      doubt in the obstetric team's ability to manage PPD. 86.1% would rather refer PPD
      cases to the psychiatrists, but saw stigma as a militating factor. Hence 77.8%
      with X2 of 65.3 would want consultation-liaison psychiatric services established
      in the centre. Concomitantly, of the 252 women assessed with EPDS, 23% were
      depressed with scores >12. CONCLUSION: It is concluded that there is need to
      update the obstetric team's knowledge on the management of PPD through Continuous
      Medical Education (CME) to which 97.2% of them agreed.

PMID- 15868976
TI  - A prospective analysis of in-patient consultation-liaison psychiatry in a
      Nigerian teaching hospital.
AB  - OBJECTIVES: To determine the pattern of psychiatric referrals over a six-month
      period categorise the psychiatric referrals into clinical syndromes and describe
      the nature of psychiatric intervention and outcome of such intervention on
      discharge and within the first three months after discharge. DESIGN: A
      descriptive prospective study. SETTING: University of Ilorin Teaching Hospital
      (UITH), Ilorin Nigeria. SUBJECTS: Forty seven inpatients (26 females and 21
      males) referred to the psychiatric department from other specialist units of the
      hospital between May and October 2001. RESULTS: The mean (+/-SD) of patients was
      33.9+/-18 years. The highest rate of referral came from the internal medicine
      department. The most common psychiatric disorders referred were acute organic
      brain syndrome (32%) and neurological disorders (15%). Psychiatric interventions
      included medication in about two-thirds of the patients and counselling in about
      a quarter. Half of the discharged patients out rightly defaulted on their first
      outpatient clinic department appointment. CONCLUSION: The study indicate the need
      for greater inter-departmental liaison learning and training activities, the need
      to emphasize training in organic psychiatry, as well as the need to establish
      community-based outreach services as a means of ensuring continuity of care for
      discharged patients.

PMID- 15868977
TI  - HBV, HIV co-infection at Kisumu District Hospital, Kenya.
AB  - BACKGROUND: Patients with dual infection of HBV and HIV are increasingly being
      recognised. The two viruses, HBV and HIV share the same route of transmission and
      HBV is more efficiently transmitted than HIV. There is evidence that HBV will
      contribute significantly to continuing morbidity and mortality within the HIV
      infected population over the coming years. This is due to the widespread
      use/accessibility of the highly active anti-retroviral (HAART) drugs hence
      patients live longer. There are few published data in the tropical region on
      these patients especially in regions where HBV and HIV are endemic. OBJECTIVES:
      To determine the prevalence of HBV, HIV co-infection in patients who presented
      with jaundice and the pattern of CD4 cell counts in these patients. DESIGN: A
      prospective, cross-sectional, descriptive study of all consecutive patients
      included in the study. SETTING: Medical wards, medical outpatient clinic and
      liver clinic, Kisumu District Hospital, Western Kenya. SUBJECTS: Five hundred and
      nineteen (261 females and 258 males) patients who had jaundice were screened for
      the study. One hundred and eighty five (110 males and 75 females) patients were
      excluded. Three hundred and thirty four patients 151 (45.2%) males and 183
      (54.8%) females were included and completed the study between August 2002 and
      October 2003. MAIN OUTCOME MEASURES: Socio-demographic data, HBsAg positive, HIV
      serology (positive or negative), CD4 cell counts, ALT and AST, IgG anti-HBc and
      IgM anti-HBc. RESULTS: The age range was 7-76 years with a mean of 36 (+/-13)
      years. The mean age for males and females was 37 (+/-13) years and 35 (+/-12)
      years respectively. One hundred and seventy seven (53%) had co-infection and 157
      (47%) had HBV mono-infection. IgG anti-HBc and IgM anti-HBc were detected in 17
      (5%) and 317 (95%) patients respectively. Of the 317 patients with IgM anti-HBc,
      177 (55.8%) had co-infection while 140 (44.2%) had HBV mono-infection (p=0.05).
      The overall mean CD4 cell count for the whole population was 391 (+/-314)
      cells/mm3. The mean CD4 cell count for patients with co-infection was lower, (120
      (+/-112) cells/mm3) than for patients with HBV mono-infection, 694 (+/-140)
      cells/mm3. The transaminases were uniformly elevated in both groups with mean AST
      of 207 (+/-147) U/L and ALT of 356 (+/-177) U/L. In the co-infection and mono
      infection groups, AST was 286 (+/-117) U/L and 306 (+/-175) U/L (p=0.23) and is
      not statistically significant, and the ALT was 338 (+/-135) U/L and 375 (+/-213)
      U/L respectively p=0.05 and the difference is statistically significant.
      CONCLUSION: HBV and HIV co-infection is recognised in this region, which is
      endemic for both viral infections. The patients with dual infection had very low
      CD4 cell counts. This will influence the choice of highly active anti-retroviral
      therapy (HAART) in favour of Lamivudine containing combinations to cover the HBV
      infection.

PMID- 15868978
TI  - Thyroid disease in a rural Kenyan hospital.
AB  - OBJECTIVES: To review the spectrum of thyroid pathology diagnoses likely to be
      encountered by surgeons working in East African hospitals. DESIGN: A
      retrospective review of all thyroidectomies performed over a three year period.
      SETTING: A rural church based hospital in Kenya. SUBJECTS: Two hundred and twenty
      two patients who underwent thyroidectomy over a three year period at Kijabe
      hospital. INTERVENTIONS: A simple protocol was used to manage thyroid disease
      involving history, clinical examination, measurement of TSH and needle aspiration
      of lesions where appropriate, and excision when clinically indicated. MAIN
      OUTCOME MEASURES: Clinical diagnosis, tribe, operation performed, pathology, and
      complications of surgery. RESULTS: Two hundred and twenty thyroidectomies were
      performed. Overall there was a malignancy rate of 11.7% (15 papillary, 11
      follicular). The commonest pathological diagnosis was multinodular goitre (47%).
      Graves' disease was a relatively common diagnosis in this series (13%). The
      mortality rate was 0.5% and the morbidity rate was 3.6%. CONCLUSION: Graves'
      disease is not as uncommon in rural Africa as previously thought. Malignancy is
      relatively common and there appears to be a change in the papillary to follicular
      cancer ratio perhaps reflecting widespread iodinisation of salt in Kenya.

PMID- 15868979
TI  - Evaluation of risk factors for mortality in perforated peptic ulcer in Ankara
      Numune Teaching Hospital, Ankara, Turkey.
AB  - OBJECTIVE: To assess the risk factor that influence mortality from perforated
      peptic ulcer. DESIGN: Retrospective study. SETTING: Ankara Numune Teaching and
      Research Hospital, Ankara, Turkey. SUBJECTS: A total of 342 patients with
      perforated peptic ulcer disease were identified from April 1997 to January 2004.
      Data for the patients were extracted from the hospital records, operative notes
      and clinic charts. MAIN OUTCOME MEASURES: Age, sex, coexisting medical illness,
      use of non-steroidal anti-inflammatory drugs (NSAID) or steroids, preoperative
      shock, delay in treatment location of ulcer size, type of operation time, albumin
      concentration postoperative complications, postoperative hospitals stay and
      mortality results for all patients were obtained. RESULTS: Patients were aged
      from 17 to 80 years (mean 63 years, median 68 years) there were 210 males and 132
      females. The mortality rate was 8.8% (30/342), and 62 patients had postoperative
      complications. Multivariate analysis showed that co-existing medical illness,
      preoperative shock, delay in treatment and low albumin concentrations were
      independent risk factors that significantly contributed to mortality. CONCLUSION:
      This study confirms co-existing medical illness, preoperative shock, delay in
      treatment and low albumin concentration as significant risk factors that increase
      mortality in patients with perforated peptic ulcers. These factors could serve as
      a guide to opine the risk and to improve the outcome in patients with perforated
      peptic ulcer. Mortality could be reduced by preventing delay in diagnosis and
      treatment for any co-existing medical illness and providing appropriate nutrition
      support.

PMID- 15868980
TI  - Clinical and radiological prevalence of skeletal fluorosis among retired
      employees of Wonji-Shoa sugar estate in Ethiopia.
AB  - OBJECTIVE: To study the clinical and radiological prevalence of skeletal
      fluorosis among the retired employees of Wonji-Shoa sugar estate. DESIGN:
      Retrospective and cross-sectional study. SETTING: Wonji-Shoa sugar estate, an
      agro-industrial estate located in the Ethiopian Rift Valley. SUBJECTS: Two
      hundred and sixty three employees of the estate who retired between 1995 and
      1996. MAIN OUTCOME MEASURES: Clinical evidence of impaired squatting, neck and
      lumbar mobility, kyphosis, and X-ray evidence of fluorosis. RESULTS: Skeletal
      fluorosis was more evident among the males (p<0.05), and the prevalence was
      higher among the factory and the agricultural workers than among the
      administrative workers (p<0.05). Clinical prevalence was 20% versus the
      radiological prevalence of 70.3%, indicating that many cases were asymptomatic.
      Impaired neck and lumbar mobility and impaired squatting significantly agreed
      with the radiological diagnosis (p<0.05) while kyphosis was not. CONCLUSION:
      Further clinical and epidemiological studies are suggested and strengthening of
      the existing defluoridation programmes within the area is recommended.

PMID- 15868981
TI  - Gender and willingness to pay for insecticides treated bed nets in a poor rural
      area in Tanzania.
AB  - OBJECTIVE: To examine socio-economic and malaria related differences between
      males and females that may cause gender differences in willingness to pay (WTP)
      for insecticide treated bed nets in a poor rural area. DESIGN: A two-week
      interval (test re-test) cross-sectional study. SETTING: Kisarawe District in
      coastal Tanzania. SUBJECTS: Two hundred and fifty one males and two hundred
      dollars females were interviewed. RESULTS: Females had about 50% of the males'
      income. The monthly average income was about US dollars 10.50 for females and US
      dollars 20.20 for males. The proportion of respondents willing to pay for an ITN,
      for both males and females, declined as the ITN prices increased (P<0.05). The
      mean maximum WTP difference between men and women, between both rounds were not
      statistically significant (p>0.05). Male respondents reported a higher mean
      number of own underfives living in the household compared to women, the
      difference was not statistically significant (P>0.8). Willingness to pay for ITN
      was found to be independent of having an under five child with recent history of
      malaria. Among both males and females, there was an association between a recent
      experience with malaria episode and WTP, p=0.05 and p=0.02 respectively. Among
      females, the proportion of those willing to pay for another person, at the lowest
      ITN price, was significantly higher in those with under five children in their
      households than in those with no underfives. This was not the case among the male
      respondents as the association was not statistically significant. CONCLUSION:
      Contrary to expectations were was no statistically significant difference in WTP
      for an ITN between females and males. Further studies that link willingness and
      ability to pay are required in rural poor population, such studies may be
      valuable inputs to government policy on and planning of ITN interventions in the
      public and private sector.

PMID- 15868982
TI  - Plasmodium falciparum parasite prevalence in East Africa: a review.
AB  - OBJECTIVES: Empirical data on malaria endemicity are rarely available for public
      domain use to guide effective malaria control. This paper describes the work
      carried in East Africa since 1997 as part of a pan-African collaboration to map
      the risk of malaria, Mapping Malaria Risk in Africa (MARA) aimed at redressing
      deficiency. DATA EXTRACTION: Studies of cross-sectional community estimates of
      Plasmodium falciparum prevalence among children aged 0-15 years were identified
      from a variety of sources including electronic searches of published material,
      manual review of pre-electronic peer reviewed journals and searches of libraries
      and archives in Kenya, Tanzania and Uganda. Each survey source, infection
      prevalence, date, longitude and latitude and survey characteristics were
      recorded. DATA SYNTHESIS: All data were subjected to a number of selection
      criteria including minimum sample sizes, samples randomly selected, community
      based surveys, age ranges of sampled communities within 0-15 years, and surveys
      that were spatially unique. Of the 2,003 survey data points identified since 1907
      in East Africa, only 503 were eligible for inclusion in the analysis dating from
      1927 to 2003. The spatial plots of the data demonstrate the paucity of
      information on malaria prevalence from a number of densely populated areas and
      highlight the concentration of empirical data in concert with research centres in
      the sub-region. CONCLUSIONS: Models are required to define malaria risk in areas
      of East Africa where no empirical data are available so that limited resources
      can be better targeted to those in greatest need.

PMID- 15868983
TI  - Stroke in sickle cell disease in Africa: case report.
AB  - Stroke, including asymptomatic cerebrovascular events, is a significant cause of
      morbidity and mortality in sickle cell disease, occurring with an incidence of 10
      to 25%. Extensive research has established that cerebral stenosis, involving the
      circle of Willis, is the most common mechanism in children. We report a child
      with sickle cell disease who presented with cortical blindness and right-sided
      hemiplegia. Computerised tomography of the brain revealed an infarct involving
      the left parietal region and extending to the occipital region. Stroke in SCD is
      multifactorial, but high-risk individuals can be identified by simple well
      established strategies such as transcranial doppler ultrasonography. There are
      approaches for both primary and secondary interventions, which have been shown to
      be effective and need to be incorporated into management guidelines for SCD
      patients. Before schemes are recommended into health care policies, research in
      the appropriate setting is required.

PMID- 15868984
TI  - Which way ahead?: I want my doctor to.... The mechanics of market research for
      medics in the millenium: special communication.
AB  - A brief description is given of the changing politico-social structure today
      involving medicine and especially the cosy personal doctor-patient relationship
      of the past which has now become triangular involving Managed Health Care
      Organisations in many cases. The Medical Practitioners' and Dentists' Board (the
      Board) appointed the Ethics Conference Committee largely composed of non-Board
      members to collect and collate information of what doctors, paramedics and the
      lay public expected from their doctors today. It is planned that the Committee's
      Report summarising this information would form the basis of the new guidelines to
      modern ethics to be published by the Board later. In this paper the mechanics,
      funding and production of the report are described but not the contents of the
      report which is still being considered by the new Board.

PMID- 15868985
TI  - [A patient with heart failure and a new murmur: not always a valvular problem].
AB  - A 78-year-old man presented with dyspnoea and a 57-year-old with chest pain. Both
      had a history of coronary atherosclerosis and were now found to have a cardiac
      murmur. They proved to have a ventricular septal rupture (VSR) that had not been
      recognized as such. In the older man, the myocardial infarction that caused the
      VSR had initially not been recognized and in both men the clinical course was
      erroneously attributed to heart failure caused by myocardial infarction alone.
      Both underwent surgical correction of the VSR; the older man died due to
      postoperative intestinal necrosis, the younger man recovered. Patients with a
      high cardiac-risk profile, atypical chest pain, symptoms ofdyspnoea and a new
      specific murmur should be suspected of having a VSR. Early recognition and
      treatment of VSR may reduce mortality significantly.

PMID- 15868986
TI  - [The Dutch Health Council report on screening for Chlamydia: too reserved].
AB  - The prevalence of sexually transmitted diseases (STDs) increased in the
      Netherlands in the years 2000-2003. A recent population-based study showed that
      Chlamydia infections were a problem in urbanised areas; prevalence in rural areas
      was low. In 2004, the Dutch Health Council advised against a national screening
      programme for Chlamydia. However, the newest figures on the distribution of
      Chlamydia infections suggest that screening in large cities might be cost
      effective. Much can be learned from the screening programme in the United
      Kingdom.

PMID- 15868987
TI  - [Primary prevention of cardiovascular disease with acetylsalicylic acid: in high
      risk patients].
AB  - In the recently published placebo-controlled 'Women's health study', use of
      acetylsalicylic acid 100 mg daily in healthy women older than 45 years protected
      against having a stroke. In men, higher doses of acetylsalicylic acid protects
      against myocardial infarction. However, risk reduction using acetylsalicylic acid
      is only clinically relevant if the absolute risk of cardiovascular disease is
      high. Countering vascular-risk factors reduces the chance of cardiovascular
      complications much more than the use of acetylsalicylic acid and therefore should
      be pursued without any reservation.

PMID- 15868988
TI  - [Metabolic syndrome: limited significance for clinical practice].
AB  - The risk factors for diabetes and cardiovascular disease are clustered in the
      'metabolic syndrome'. The introduction of working definitions of this syndrome,
      all including dyslipidaemia (high triglycerides and low HDL cholesterol level),
      hypertension, hyperglycaemia and a measure of fat distribution or obesity, has
      enabled descriptive studies. Prospective population studies report an
      approximately two-fold increased risk of cardiovascular disease in subjects with
      the metabolic syndrome, with a linear increase in risk with increasing number of
      risk factors. So far, there is no solid evidence that insulin resistance is the
      main cause of the syndrome. A number of alternative or contributing mechanisms
      have been proposed, including cortisol metabolism and microvascular dysfunction.
      The concept of the metabolic syndrome has improved public awareness. Its utility
      in clinical practice, however, is under debate. Reduction of obesity by life
      style changes and treatment of individual risk factors is still the best line of
      action.

PMID- 15868989
TI  - [The metabolic syndrome: a cluster of vascular risk factors].
AB  - The metabolic syndrome is a cluster of several vascular risk factors (impaired
      glucose metabolism, dyslipidaemia, hypertension and central adiposity). The
      prevalence of the metabolic syndrome is high, varying between 10 and 40%
      depending on age and sex. This prevalence will increase in the years to come due
      to the increased prevalence of overweight/obesity. To identify the metabolic
      syndrome, there is a readily applicable definition for daily clinical practice,
      i.e. the presence of three or more of the following characteristics:
      hyperglycaemia, hypertension, low plasma HDL cholesterol level, high plasma
      triglyceride level and central adiposity. The underlying pathophysiology is not
      fully clarified, but insulin resistance plays an important role in this syndrome.
      The metabolic syndrome is associated with increased cardiovascular morbidity and
      mortality and an increased risk for the development of diabetes mellitus type 2.
      In subjects with one or two components of the metabolic syndrome and in patients
      with manifest vascular disease, it seems advisable to be alert to the presence of
      the other components in order to either diagnose or exclude the metabolic
      syndrome. Although clinical evidence is lacking, from a pathophysiological point
      of view it seems reasonable to focus the treatment on reducing insulin
      resistance, which can be achieved by weight reduction and an increase in physical
      activity. Treatment of the individual risk factors may also be considered,
      depending on the degree of vascular risk.

PMID- 15868990
TI  - [Microvascular dysfunction as an explanation for the metabolic syndrome].
AB  - The metabolic syndrome is a cluster of mutually related risk factors that confers
      an increased risk for both type 2 diabetes mellitus and cardiovascular disease.
      Although the metabolic syndrome seems to have multiple aetiological factors,
      microvascular dysfunction is a potential explanation for the above-mentioned
      cluster of multiple metabolic risk factors such as hypertension, insulin
      resistance and glucose intolerance. Microvascular dysfunction leads not only to
      increased peripheral vascular resistance and blood pressure, but may also
      decrease the insulin-mediated glucose uptake in muscles. The different effect on
      the microcirculation may explain why some antihypertensive drugs (beta-blockers)
      lead to an increased incidence of type 2 diabetes, whereas others (angiotensin
      converting enzyme (ACE) inhibitors) are associated with a decrease of that risk.

PMID- 15868991
TI  - [Tissue-specific changes in cortisol metabolism and their potential role in the
      metabolic syndrome].
AB  - The intracellular enzyme IIbeta-hydroxysteroid dehydrogenase (IIbetaHSD)
      catalyses the interconversion between the biologically-active cortisol and
      inactive cortisone. There are two distinct isozymes: IIbetaHSD type I behaves
      predominantly as a reductase in vivo and activates cortisone into cortisol,
      whereas IIbetaHSD type 2 functions as a dehydrogenase and inactivates cortisol
      into cortisone. At tissue level, IIbetaHSD type I amplifies the effect
      ofglucocorticoids, whereby free cortisol is generated from the relative excess of
      circulating free cortisone. Both animal and human studies have demonstrated that
      alterations in IIbetaHSD type I activity in adipose tissue and liver are
      associated with the metabolic syndrome, thus possibly reflecting a tissue
      specific (omental) Cushing's syndrome. Pharmacological inhibition of IIbettaHSD
      type I activity provides an interesting mechanism for the development of novel
      therapeutic agents for type-2 diabetes mellitus.

PMID- 15868992
TI  - [Diagnostic image (236). A woman with acute unilateral swelling of the face].
AB  - An 88-year-old woman developed right-sided facial swelling due to acute
      sialoadenitis of the parotid and submandibular glands.

PMID- 15868993
TI  - [The risk of pelvic inflammatory disease associated with urogenital infection
      with Chlamydia trachomatis; literature review].
AB  - OBJECTIVE: To determine the rate of PID in women with genital Chlamydia
      trachomatis infection. DESIGN: Systematic literature review. METHOD: MEDLINE and
      EMBASE were searched over the years 1975-2003 using the keywords 'Chlamydia
      trachomatis', 'complication', 'pelvic (inflammatory disease)', 'PID',
      'endometritis', 'adnexitis', and 'salpingitis'. The reference lists ofthe
      articles retrieved were checked for other relevant publications. The PID
      complication rate was determined, as were the characteristics of the study
      populations and the validity of the diagnostic methods and outcome measures used.
      RESULTS: 9 prospective studies were identified. The rate of PID in women with a
      genital C. trachomatis infection varied between o and 72%. Asymptomatic women who
      were diagnosed with C. trachomatis infection in general screening had the lowest
      rate of PID: 0-4%. PID occurred in 12-30% of symptomatic women or women with a
      higher risk of having an STD (e.g. visitor of an STD clinic, double-infection
      with gonorrhoea, high risk assessed by questionnaire, having a partner with
      symptomatic C. trachomatis infection). Women who underwent legal abortion had the
      highest rate of PID (27-72%). CONCLUSION: The PID rate in women with C.
      trachomatis varied considerably. Risk depended on whether the infection was
      symptomatic and the prior probability of having an STD.

PMID- 15868994
TI  - [Anaemia in two infants due to fetomaternal transfusion].
AB  - In two neonates, a boy suffering from persistent pulmonary hypertension of the
      newborn and a girl with fetal distress, massive fetomaternal haemorrhage was
      diagnosed (290 ml). In both cases fetal monitoring showed a sinusoidal heart rate
      pattern and the Kleihauer-Betke test was positive. Both children were intubated
      and ventilated and were given an erythrocyte transfusion. They both recovered.
      Differentiation between acute and chronic fetomaternal haemorrhage is essential
      when deciding on treatment: blood transfusion in acute fetomaternal haemorrhage
      and exchange transfusion in chronic fetomaternal haemorrhage with normoor
      hypervolemia. Differentiation is difficult. Little is known about the prognosis
      of fetomaternal haemorrhage. Because of the nature of perinatal problems and the
      possibility of neurological damage, long-term follow-up is recommended.

PMID- 15868995
TI  - [Serotonin syndrome as a result of concomitant use of paroxetine and
      sumatriptan].
AB  - A 65-year-old woman was referred with confusion, strange behaviour, sinus
      tachycardia, hypertension and hyperthermia. She had been taking sumatriptan and
      paroxetine and recovered completely after discontinuation of these agents. The
      diagnosis was 'serotonin syndrome', a result of overstimulation of 5-HT(1A)
      receptors in the raphe nuclei of the brainstem. It is a complication of the use
      of serotonergic agents and is associated with the rapid onset of mental,
      autonomic and neurological symptoms. Treatment consists of discontinuation of the
      suspected medication and, in severe cases, providing symptomatic relief. Given
      the frequent prescription of (combinations of) serotonergic agents, one should be
      aware of this complication.

PMID- 15868996
TI  - [Severe insuffiency of the aortic and tricuspidal valves associated with
      pergolide use].
AB  - A 58-year-old woman with Parkinson's disease was treated with high-dose pergolide
      for 10 years. After the addition of citalopram, a selective serotonin reuptake
      inhibitor, to treat an anxiety disorder, she developed cardiac decompensation
      that was most likely related to typical pergolide-related fibroproliferative
      abnormalities of the tricuspidal, aortic and mitral valves, without
      cardiomyopathy or coronary heart disease. The aortic and tricuspidal valves were
      replaced with prosthetics and pergolide was switched to ropinirol. At a control
      visit after one year, patient's heart function was stable. Pergolide is an ergot
      derived dopamine agonist used in the treatment of Parkinson's disease and
      restless-legs syndrome. In 2002, it was first associated with heart-valve
      defects. Patients treated with pergolide should be monitored for clinical signs
      of heart-valve failure. If there is no evidence of heart-valve defects, then
      regular monitoring of cardiac function is indicated. In case of indications of
      heart-valve failure pergolide should be discontinued. In some cases the heart
      valve abnormalitites are reversible.

PMID- 15868997
TI  - [Non-incarcerated inguinal hernia in children: operation within 7 days not
      necessary].

PMID- 15868998
TI  - The optimal injection time of alfentanil for blunting circulatory responses to
      tracheal intubation.
AB  - BACKGROUND: The aim of this study is to investigate the optimal injection time of
      alfentanil during induction of anesthesia to blunt the circulatory responses
      induced by laryngoscopy and tracheal intubation. METHODS: Seventy-five patients
      of ASA class I or II were randomly assigned to five groups. Group I was the
      placebo group in which the patients received normal saline 2 ml just before
      induction. Patients in groups II, III, IV and V received alfentanil 10 microg/kg
      at 5, 3, 1 and 0.5 min before intubation respectively. Anesthesia was maintained
      with 1.5% isoflurane and nitrous oxide in 50% oxygen (2:2 L/min). The patients'
      heart rate and blood pressure before and after intubation were documented and
      compared. The occurrence of adverse effects was also recorded. RESULTS: Patients'
      demographic data, baseline hemodynamic profile and the laryngoscopic time did not
      differ among the five groups. The patients in groups II, III and IV showed
      decreased heart rate compared with group I within 3 min after intubation. The
      patients in group V like those in group I did not show a reduction in heart rate
      1 min after intubation. The patients in groups II, III, IV and V all showed
      reduced systolic blood pressure and rate-pressure product (RPP) 2 min after
      intubation. The occurrence of hypotension and bradycardia was not different among
      the five groups; hypertension and high RPP were less in groups II, III and IV as
      compared with group I. Ninety-three percent patients in group II and group III
      suffered from dizziness after alfentanil administration. One patient in group II
      had nausea and another one patient displayed hypoxemia after alfentanil
      administration. CONCLUSIONS: Considering equal effectiveness and fewer side
      effects, one minute before intubation is the optimal injection time of alfentanil
      to blunt the circulatory responses induced by laryngoscopy and tracheal
      intubation.

PMID- 15868999
TI  - A novel long-acting analgesic: buprenorphine palmitate in rats.
AB  - BACKGROUND: A long-acting analgesic may be particularly desirable in patients
      with long-lasting pain. In order to provide a long-acting analgesic effect, a
      novel buprenorphine ester, buprenorphine palmitate, was synthesized in our
      laboratory. The aim of the study was to evaluate whether the ester had a long
      lasting effect. METHODS: The antinociceptive effects (dose-range studies) of
      buprenorphine HCl and buprenorphine palmitate were evaluated using the plantar
      test in Sprague-Dawley rats. RESULTS: We found that intramuscular injection of
      buprenorphine HCl 0.05, 0.1 and 1 micromol/kg in rats produced dose-related
      antinociceptive effects of 2, 3, and 4 h, respectively. Intramuscular injection
      of buprenorphine palmitate 1, 5, and 10 micromol/kg also produced dose-related
      antinociceptive effects of 72, 76 and 78 h, respectively. On an equimolar basis
      of 1 micromol/kg, the durations of action of intramuscular buprenorphine HCl and
      buprenorphine palmitate were 4 and 72 h, respectively. CONCLUSIONS: Intramuscular
      injection of buprenorphine palmitate in rats produced a long-lasting
      antinociceptive effect which was much longer (18-fold) than did intramuscular
      buprenorphine HCl.

PMID- 15869000
TI  - The antinociceptive and anti-inflammatory effects of a long-acting depot
      formulated ketorolac in rats.
AB  - BACKGROUND: Currently, no long-acting nonsteroidal anti-inflammatory drug is
      available clinically for the treatment of long-lasting pain. The aim of the study
      was to evaluate the antinociceptive and anti-inflammatory effects and duration of
      action of a novel depot formulation of ketorolac benzyl ester in sesame oil.
      METHODS: Two studies in Sprague-Dawley rats were carried out. In study 1, the
      antinociceptive and anti-inflammatory effects of intramuscular ketorolac
      tromethamine were evaluated. In study 2, the antinociceptive and anti
      inflammatory effects of intramuscular ketorolac benzyl ester were evaluated. The
      antinociceptive effect was evaluated using the paw pressure test, whereas the
      anti-inflammatory effect was evaluated by the paw edema test. RESULTS:
      Intramuscular ketorolac tromethamine at 24, 80, and 240 micromol/kg (in saline)
      produced significant antinociceptive and anti-inflammatory effects with duration
      of action around 6 to 8 h. Ketorolac benzyl ester at a dose of 240 micromol/kg
      (in oil) produced significant long-acting antinociceptive and anti-inflammatory
      effects with duration of action of 56 h. CONCLUSIONS: Intramuscular injection of
      ketorolac benzyl ester (in sesame oil) in rats produced antinociceptive and anti
      inflammatory effects which were 7-fold longer in duration of action than
      ketorolac tromethamine (in saline).

PMID- 15869001
TI  - NF-kappaB inhibitors significantly attenuate the transcription of high affinity
      type-2 cationic amino acid transporter in LPS-stimulated rat kidney.
AB  - BACKGROUND: Sepsis-induced renal failure is closely related to inducible nitric
      oxide synthase (iNOS) upregulation and nitric oxide (NO) overproduction. Trans
      membrane L-arginine transportation mediated by type-2 cationic amino acid
      transporter (CAT-2) isozymes, including CAT-2, CAT-2A, and CAT-2B, is one of the
      crucial mechanisms that regulate NO biosynthesis by iNOS. We previously had shown
      that endotoxemia significantly upregulated renal CAT-2 and CAT-2B but not CAT-2A
      expression. This study was, thus, conducted to further explore the role of
      nuclear factor-kappaB (NF-kappaB) in regulating the expression of CAT-2 isozymes
      in lipopolysaccharide (LPS)-treated rat kidney. METHODS: Adult male Sprague
      Dawley rats were randomly given intra-peritoneal injections of normal saline
      (N/S), LPS, LPS plus NF-kappaB inhibitor pre-treatment (PDTC, dexamethasone, or
      salicylate), or an NF-kappaB inhibitor alone. The rats were sacrificed at 6 hours
      after LPS injection and enzyme expression and renal injury were examined.
      RESULTS: Renal iNOS, CAT-2, and CAT-2B were significantly upregulated in LPS
      stimulated rat kidney. NF-kappa B inhibitors significantly attenuated this
      upregulation induced by LPS and resultantly attenuated renal NO biosynthesis and
      renal injury induced by LPS. In contrast, renal CAT-2A expression was not
      affected by either LPS or NF-kappaB inhibitors. CONCLUSIONS: LPS co-induces iNOS,
      CAT-2 and CAT-2B expression in LPS-stimulated rat kidney. Furthermore, inhibition
      of NF-kappaB significantly attenuates NO biosynthesis through inhibition of iNOS,
      CAT-2, and CAT-2B, and, in turn, significantly reduces endotoxemia-induced renal
      injury.

PMID- 15869002
TI  - Conscious sedation in gastrointestinal endoscopy.
AB  - In recent years, the incidences of stomach and colon cancers have ranked within
      the top fives of all malignancies in Taiwan. To say healthwise, regular
      gastrointestinal (GI) endoscopic examinations are recommended, as they are the
      best way for early detection. However, unpleasantness of and terrible experience
      from the examination greatly discourage the acceptance of many people even of the
      suspected groups. Now, the administration of sedative or analgesic to achieve the
      so called "conscious sedation" during GI endoscopy which brings about better
      tolerability and improves general acceptance offers a more satisfactory service.
      In this article, the related issues about preprocedure evaluation, preparation,
      medications and complications of conscious sedation in GI endoscopy are discussed
      after review.

PMID- 15869003
TI  - Acute cardiovascular collapse after pericardial drainage in a patient with aortic
      dissection.
AB  - Proximal aortic dissection is frequently associated with cardiac tamponade. The
      treatment sometimes is difficult. We present a 69-year-old female patient who
      after repeated episodes of syncope received an open drainage of pericardial
      effusion that ended in a fatal outcome. She was also known to have mural thrombi
      in the aorta. However, preanesthetic trransesophageal echocardiography revealed
      besides pericardial effusion, also dilatation of aortic root which compressed
      both atria. She developed sudden cardiovascular collapse following drainage of
      pericardial effusion to which she succumbed in spite of vigorous resuscitation.
      We suggest that the patients with cardiac tamponade complicated by aortic
      dissection must receive direct aortic repair together with intraoperative
      pericardial drainage. Selective or single pericardiocentesis should better be
      avoided.

PMID- 15869004
TI  - Sudden hearing loss after general anesthesia--a case report.
AB  - Hearing impairment following many types of neuraxial anesthetic techniques has
      alreadly been reported previously. However, postoperative sudden hearing loss
      after general anesthesia (excluding cardiopulmonary bypass cases) for nonotologic
      surgery is rarely reported. We present a 42-year-old female patient, who
      underwent ophthalmologic surgery under general anesthesia because of diabetic
      retinopathy and developed postoperative hearing loss of the left ear.
      Sensorineural hearing loss was diagnosed and it has persisted without improvement
      for 2 years following surgery.

PMID- 15869005
TI  - Delayed recovery of radial nerve function after axillary block in a patient
      receiving ipsilateral ulnar nerve transposition surgery.
AB  - A 68-year-old female who underwent right ulnar nerve transposition surgery under
      axillary block (AB) by dual-technique (paresthesia and axillary artery
      penetration techniques) developed postoperative wristdrop. Physical examination
      showed local hematoma formation with ecchymosis at her right axillary region.
      Both ultrasonography and nerve conduction studies on her brachial plexus revealed
      neither direct hematoma compression, intraneural hematoma, nor peripheral
      neuropathy. Fortunately, she was completely restored to her right hand function
      20 h after anesthesia, and was discharged without sequelae 17 days later. In this
      case, delayed recovery of radial nerve function after AB was suspected and the
      mechanism which led to this unusualness is discussed.

PMID- 15869006
TI  - Anesthetic approach to the Dyke-Davidoff-Masson syndrome--a case report.
AB  - The so-called Dyke-Davidoff-Masson syndrome (DDMS) is a rare disorder of cerebral
      hemiatrophy. The clinical presentation may consist of facial asymmetry,
      contralateral atrophy (including the trunk, and the extremities) and hemiparesis,
      speech difficulties, mental retardation, and epilepsy. Because it involves
      multiple systems, especially problem of the airway, occult myopathy, and seizure
      disorder, anesthesia for such a patient is a challenge to any anesthesiologist.
      However, there are no clinical reports which concern the anesthetic management of
      such patients in the literature. We herein report a 5-year-old girl, a sufferer
      of DDMS, scheduled for burr trephination. The successful anesthetic management is
      brought forward with highlights of inference from the experience.

PMID- 15869007
TI  - Airway obstruction caused by endotracheal tube cuff herniation during creation of
      tracheal stoma.
AB  - We report an unusual case of airway obstruction caused by herniation of
      endotracheal tube (ETT) cuff in a 62-year-old male who underwent surgery for
      hypopharyngeal carcinoma. During the procedure of creating a tracheal stoma, a
      new oral ETT was inserted by the surgical team to the lower portion of the
      trachea through the cut opening to replace the old for ventilation and prevention
      of soiling of the airway. Upon resumption of surgical manipulation, right
      endobronchial intubation was disclosed. The ETT cuff was therefore repositioned
      and reinflated, but airway obstruction persisted in spite of tube obstruction
      being ruled out by successfully passing a suction catheter through the ETT. After
      deflating the cuff the obstruction was resolved, and ventilation was eased. Thus
      the ETT was replaced with another new one and careful scrutiny made after the
      event revealed a herniating cuff due to manufacturing defect. It was conceivable
      that endobronchial intubation with over-inflation of the tube cuff may cause cuff
      herniation, particularly when surgical manipulation was active at the adjacency,
      in spite of the use of a modern tube with low-pressure high-volume cuff.
      Performing the "cuff deflation test" is the simple way to diagnose cuff
      herniation. Awareness of this condition, especially when anesthesiologists lose
      direct control of the airway during such procedures is important because
      undesirable complications can be prevented through quick decision and action.

PMID- 15869008
TI  - Cardiovascular effects of aldosterone.
AB  - Aldosterone plays an important role in the pathophysiology of sodium/potassium
      and water homeostasis of the body. It is nowadays clear that aldosterone
      contributes also to the development of cardio-vascular diseases, such as
      hypertension, left ventricular hypertrophy, heart failare, renal failare and
      others, by direct effets on vesels and the heart. The global view on
      pathophysiology, on harmful effects of aldosterone and on aldosterone in
      hypertension and heart failare is presented.

PMID- 15869009
TI  - Carvedilol--a beta-blocker with considerable antiaggregatory effect on human
      blood platelets.
AB  - BACKGROUND: Activated blood platelets play a key role in the genesis of many
      pathological states. Several studies have documented that beta-blockers can
      influence platelet aggregation. Carvedilol, a third generation non-selective
      agent with vasodilatory properties, is successfully used in pathological states
      accompanied with platelet hyperreactivity, however information on its
      antiplatelet activity is lacking. OBJECTIVES: The aim of this study was to
      analyse the in vitro effect of carvedilol on aggregation of human blood
      platelets, to compare this effect with the effect of propranolol and atenolol,
      and to determine whether its suggested antiaggregatory effect was accompanied
      with reduced thromboxane B2 formation. Moreover, some physico-chemical parameters
      of the drugs tested were calculated and compared. METHODS: Platelets were
      isolated by differential centrifugation and platelet aggregation was measured by
      the turbidimetric method. The amount of thromboxane B2 was measured by the
      radioimmunoassay method. Physico-chemical parameters of the drugs tested were
      calculated using the computer programme Hyperchem. RESULTS: Carvedilol and
      propranolol inhibited platelet aggregation in the rank order of stimuli: PMA >
      thrombin > A23187 > epinephrine. The reduction was accompanied by inhibition of
      thromboxane B2 formation. In comparison to propranolol, carvedilol was more
      effective, with the exception for aggregation stimulated with ADP. Atenolol did
      not affect any platelet function tested. From the drugs studied, the molecule of
      carvedilol was found to possess the highest partition coefficient, the highest
      index of molar refractivity, and the lowest dipole moment. CONCLUSION: Our study
      found carvedilol to be more potent than propranolol and atenolol in inhibiting
      platelet aggregation and thromboxane B2 production. This may be due to the
      different structure and more convenient physico-chemical parameters of the
      carvedilol molecule.

PMID- 15869010
TI  - Complications of central venous catheterization in hemodialysis patients.
AB  - When an acute hemodialysis in a patient with no arterio-venous shunt is needed,
      placement of a central venous catheter (CVC) is the ultimate solution. Otherwise
      a simple procedure may present with numerous complications. The authors describe
      their experiences with early and late complications of CVC in 106 patients.
      Complications occured in 20 patients out of 106, a trend comparable or better
      than previously published by various authors. The most frequent (16 cases)
      complication was a catheter-related sepsis. All patients recovered, however in
      two patients a replacement of CVC was necessary due to the failure of antibiotic
      treatment. The authors describe the possibility of maintaining the CVC in situ
      longer than the recommended 1--2 weeks period without more frequent
      complications. This finding may result from an excellent service provided by the
      dialysis nurses and from patient education.

PMID- 15869011
TI  - A study of the symptomatology of hypertrophied anal papillae and fibrous anal
      polyps.
AB  - BACKGROUND: The presence of Hypertrophied anal papillae and fibrous anal polyps
      are often ignored in proctology practice. But the experience is that they tend to
      produce minor but disturbing symptoms. This study is aimed to assay the impact
      and utility of attending these two conditions concurrently while dealing with
      cases of fissure in ano. PATIENTS AND METHODS: The study was carried out in 136
      patients with chronic anal fissure having concomitant hypertrophied anal papillae
      or fibrous anal polyps. After relieving sphincter spasm by sphincterotomy, the
      polyps or papillae were destroyed using the radio frequency device. A comparison
      was made for the associated complaints like pruritus, pricking sensation,
      wetness, crawling sensation in the anus etc. before and after the removal of
      papillae or polyps by an independent observer blinded to the procedure. RESULTS:
      After one month of the procedure, the associated symptoms were reduced to a
      significant extent along with a nearly total decline in the primary complaints of
      pain and bleeding. There was significant reduction in pruritus (p=0.0003),
      discharge per anus (p=0.0006), crawling sensation in the anus (p=0.0004) and that
      of incomplete evacuation (p=0.001) At the follow up after 18 months, only 9 % of
      patients had recurrence of either anal fissure or symptoms like pruritus.
      CONCLUSION: This study establishes that removal of hypertrophied anal papillae
      and fibrous polyps should be carried on a routine basis during surgical treatment
      of anal fissure. This would add to the effectiveness and completeness of the
      procedure.

PMID- 15869012
TI  - Variations of nerve roots of the brachial plexus.
AB  - OUTCOME: Aberrations observed during surgical treatments inspired us to initiate
      the investigation of variations in the formation of brachial plexus. MATERIAL AND
      METHODS: 100 brachial plexuses in 50 cadavers were examined for the incidence of
      neural variations. We examined the involvement of the C4 root and eventually of
      that of Th2 root, as well as various deviations in the exit of individual roots
      and their branches from the backbone. We have focused also on their paths,
      anastomoses, on their thickness or on their eventual absence. In addition to the
      anatomical complexity and variability, the specifics of motor innervation related
      to diagnostics are also emphasized. The attention is paid to the mechanisms and
      morphological reasons of the occurrence of specific types of injuries. RESULTS:
      Prefixed type was present in 24 cases (48 %), postfixed type was present just in
      one case. Aberrations have been observed in 14 cases (28 %). They occurred more
      frequently on the left side (9 cases) followed by two-sided aberrations (4
      cases). CONCLUSION: This study enabled to identify and describe exceptional and
      hitherto undescribed anatomical variations in the formation of nerve roots of
      brachial plexus.

PMID- 15869013
TI  - Selected hormones levels in individuals with endothelial dysfunction and insulin
      resistance.
AB  - AIM: To determine possible differences in selected serum hormones levels related
      to endothelial function and insulin sensitivity. METHODS: Ghrelin, insulin,
      serotonin, growth hormone, IGF-1, leptin and adiponectin serum levels were
      determined in a group of 83 adults (40 women, 43 men) with a mean age 49.4+/-4.6
      years. Total ghrelin, insulin and serotonin levels were measured using RIA,
      growth hormone and leptin using IRMA and human adiponectin was measured using
      ELISA. Results were associated with BMI, calculated as kg/ m2, endothelial
      function, determined by ultrasound measured flow mediated vasodilatation of
      brachial artery, and with insulin resistance, calculated by IR HOMA index.
      RESULTS: We found no difference in age comparing subjects with (ED+) and without
      (ED-) endothelial dysfunction, neither comparing subject with (IR+) and without
      (IR-) insulin resistance. In individuals ED+ and IR+ a higher BMI, serum leptin
      and insulin levels and lower ghrelin, growth hormone and adiponectin levels were
      found. Subject with ED presented with a higher serum serotonin level compared to
      subjects without ED. This difference was not found in individuals with and
      without IR. CONCLUSION: Lower ghrelin, growth hormone and adiponectin levels
      along with higher insulin and leptin levels may contribute to the progression of
      endothelial dysfunction and insulin resistance.

PMID- 15869014
TI  - [Failing students in nursing--a new rubric is being offered].

PMID- 15869015
TI  - [Demands on professional nursing staff in institutions for dialysis from the view
      of male and female patients--the results of a survey by means of Critical
      Incident Technique].
AB  - Contemporary models of competence in nursing are usually based on the questioning
      of nursing staff and therefore reflect their professional self-image. Our
      research focuses on the views of male and female patients on the relevant
      competencies of professional nursing staff. The "Critical Incident Techniqu"
      (CIT) (Flanagan, 1954) was applied to reveal relevant demands according to the
      patients' point of view. This technique has proven to be a suitable method for
      the reflection of nursing practice in this field of research and has provided
      realistic descriptions of staff behaviour. Nursing in the field of dialysis was
      chosen because of the specialized qualifications on staff needed and the high
      expectations assumed in this care. The CIT-interviews of one female and five male
      patients were transcribed and the content was analysed. Two main fields of
      demands were identified: "soft skills" and "hard skills". The patients especially
      stressed the demands on communicative and empathic competence ("soft skills").
      Further research may be useful to validate the results with a larger sample.

PMID- 15869016
TI  - [Continuity of care--the perspective of nurses responsible for
      Pflegeuberleitung].
AB  - Until a few years ago, continuity of care in connection with a client's
      transition from one care setting to another was not considered part of the
      primary objectives of the health system, due to a strict division of intramural
      and extra-mural care systems. Nowadays, epidemiological as well as sociographic
      developments have changed the situation fundamentally. As their common main
      objective, the different approaches towards Pflegeuberleitung focus on the
      management of interfaces by reducing breaks in co-ordination, thereby improving
      the quality of the service. As part of an extensive research project in three
      hospitals from March 2000 to February 2002 on securing continuity of care through
      Pflegeuberleitung, specific attention was rendered to the views of nurses
      involved in it. One of the main findings emerging from the self-assessment
      focuses on the uncertainty of the nurses involved in Pflegeuberleitung about
      their own work within the hospital context. This reflects the still insufficient
      integration of Pflegeuberleitung in the hospital system. Here, organization is
      still centered on "discharge" as the main work aim rather than the patients'
      interests reaching beyond system borders.

PMID- 15869017
TI  - [Continuity of care--the perspective of patients and their relatives].
AB  - As part of an extensive research project on securing continuity of care through
      Pflegeuberleitung, data on experiences of patients and their relatives regarding
      discharge from hospital were collected and analysed by means of a qualitative
      study. Ten focused interviews were conducted and analysed with five patients and
      five relatives, respectively. From the results of the patient interviews, the
      subjective experience of being ill was identified as a main issue, constituting a
      dimension which pervades all other categories of the results. Patients judge
      nursing measures regarding the discharge planning in the light of this dimension.
      The results of the interviews with relatives indicate the lack of
      interdisciplinary cooperation and coordination. Relatives complain about the
      missing attempts to come to agreements and about their perspective not being
      considered regarding care needs as well as the date of discharge. There is a need
      for the development of new approaches to care and treatment in the hospital which
      allow for the patient's and the relatives' participation and co-shaping, thereby
      recognizing an altered understanding of the respective roles. In order to achieve
      systematic integration of the clients' perspectives, thus securing individual
      continuity of care, programmes for professional consultancy play an important
      part of these new approaches.

PMID- 15869018
TI  - [Continuity of care by Pflegeuberleitung? Results of participant observation].
AB  - Continuity of care between health care institutions is of increasing importance.
      In a two-year research project on this topic extensive participant observation
      was carried out for data gathering in three hospitals in Dusseldorf (Germany). In
      each institution four patients were observed until their discharge and all
      interactions between them and health care professionals were documented using a
      semi-structured data-gathering instrument. Furthermore, the researchers
      questioned the involved professionals after each situation. Altogether a total of
      980 situations were documented during 100 shifts, thus professional activities
      aiming at continuity of care can be regarded as extensively covered. The results
      show that care professionals (nurses, physicians, social workers etc.) in the
      three participating hospitals only incompletely assess individual needs or even
      fail to do so at all. In addition, there is no regular interprofessional
      collaboration and the professionals' horizon is essentially limited to their own
      institution. Patients and their relatives are not systematically involved and
      their views rarely considered. Two cases are used as examples to illustrate these
      aspects. A third example shows that also successful processes were observed. In
      most cases, however, the implicit logic of the hospital system dominates over
      individual needs and therefore a successful continuity of care processes cannot
      be assumed. Finally, the necessity for a fundamental change of this
      counterproductive systems logic is briefly discussed.

PMID- 15869019
TI  - [Selected results of an evaluation study on a Viennese model project: discharge
      management in hospitals by home care nurses--the view of patients and their
      families].
AB  - In recent years, demographic developments, changes in the financing of hospitals
      as well as demands for integrated care approaches by health and social policy
      makers have brought the issue of an improved hospital discharge management to the
      forefront. The article discusses results of an evaluation study of a Viennese
      model project on indirect discharge management at the Kaiser-Franz-Josef-Hospital
      in Vienna. The service coordinated at hospital level is provided by ambulant
      nurses for specific wards of the hospital. The data of the study show that the
      target group consists primarily of old patients with multiple illnesses requiring
      home care services as well as patients being transferred to nursing homes. The
      evaluation proves that patients and their families are highly satisfied with the
      service. Dedicated contact persons really provide crucial support to patients and
      relatives in this emotionally distressed transitional period, seeing their
      clients through difficult decisions. Discharge managers and clients jointly find
      out actual needs of the patient and discuss possible solutions considering
      available resources of the respective lay system and ways to strengthen it. The
      outcome is a tailor-made care package, coordinated across professional services,
      matching the patients' needs and resources. Moreover the study illustrates that
      concepts of transitional nursing care require extraordinary skills and
      competences on the part of the discharge manager, currently not covered by the
      Austrian curriculum for nurses.

PMID- 15869020
TI  - The role of psychopharmacotherapy in improving the long-term outcome of
      schizophrenia.
AB  - Drs. Alam and Janicak briefly review the current indications and problems
      associated with the use of atypical antipsychotics in schizophrenia treatment.
      When called for, they may be augmented by mood stabilizers, such as lithium;
      antidepressants; benzodiazepines (for rapid tranquillization during agitated
      psychotic episodes); and stimulants, even nicotine, to improve cognition. Even
      though extrapyramidal side effects are less frequent and less intense that those
      seen with traditional antipsychotics, they do occur; the authors spell out the
      attributes of those patients who are most vulnerable. Clinicians should also look
      for weight gain and the risk of activating or aggravating type 2 diabetes in
      patients, as well as cardiac risk involving prolongation of the QTc interval.
      Because, despite of modern approaches to treatment, 80% of patients end up
      rehospitalized and only 1 in 3 can be said to have a good level of socialization,
      active measures must be taken to ensure continuity of care, monitoring for
      prodromal symptoms, early intervention, and psychosocial rehabilitation.

PMID- 15869021
TI  - Dehydroepiandrosterone (DHEA) augmentation in the management of schizophrenia
      symptomatology.
AB  - Neurosteroids, such as dehydroepiandrosterone (DHEA) and DHEA-sulfate (the most
      abundant steroid in the body), regulate neuronal functions by influencing
      neuronal excitability. Prominent effects are exerted on the gamma-aminobutyric
      (GABA) receptors. DHEA has demonstrated efficacy in improvement of mood in
      humans, especially in middle-aged and elderly individuals. In the author's study,
      administering DHEA to patients with schizophrenia who had moderate to severe
      negative symptoms and who were maintained on antipsychotic medications induced
      significant improvement, more so in women and corresponding to increased plasma
      levels of DHEA and DHEA-S. Possible mechanisms of action include enhanced
      dopamine release, enhanced responsiveness at the N-methyl D-aspartate (NMDA)
      receptor, facilitation of sigma receptor activity, selective potentiation of
      dopaminergic neurotransmission, and a general anxiolytic action. Side effects are
      reviewed, and the currently experimental status of DHEA augmentation is
      emphasized.

PMID- 15869022
TI  - Atypical antipsychotic therapy and hyperlipidemia: a review.
AB  - Ziprasidone (Geodon), risperidone (Risperdal), and aripiprazole (Abilify) appear
      to be associated with a relatively low risk for hyperlipidemia, whereas
      quetiapine (Seroquel), olanzapine (Zyprexa), and clozapine (Clozaril) are
      associated with a relatively high risk for hyperlipidemia. Possible underlying
      causes of lipid dysregulation include weight gain, dietary changes, and glucose
      intolerance. Given the multiple cardiovascular risk factors reported for patients
      with schizophrenia, great care must be exercised to minimize the additional risk
      for hyperlipidemia when choosing antipsychotic therapy. It is recommended that a
      lipid panel be obtained at baseline for all patients with schizophrenia and
      annually thereafter for patients taking relatively low-risk agents or quarterly
      thereafter for patients taking relatively high-risk agents. Patients with
      persistent dyslipidemia should be referred for lipid-lowering therapy or switched
      to a less lipid-enhancing antipsychotic agent.

PMID- 15869023
TI  - Non-nicotine pharmacotherapies for nicotine dependence.
AB  - The smoking rate for patients with schizophrenia reaches as high as 90% in
      clinical samples, 70% for patients with bipolar disorder, and 40% to 50% for
      patients with major depression and anxiety disorders. Because it is a significant
      health hazard, smoking should be aggressively discouraged, and, in this group of
      patients, a combination of behavioral therapy and pharmacotherapy currently
      offers the best option. Nicotine provides a number of benefits, including anxiety
      relief, increased alertness, and improved cognitive functioning. It alters a wide
      range of central nervous system neurotransmitters. Unfortunately, nicotine
      readily establishes physiological dependence. In cessation efforts, transdermal
      nicotine patches and nicotine gum are helpful adjuncts. The primary FDA approved
      non-nicotine pharmacotherapy agent is bupropion (Zyban). Studies summarizing the
      effectiveness (or lack thereof) of other (off-label) agents, such as tricyclic
      antidepressants, MAO-Inhibitors, SSRIs, and clonidine, are cited.

PMID- 15869024
TI  - Recognizing and dealing with depression with psychosis.

PMID- 15869025
TI  - ["Preventing obesity is to encourage good health practices". Interview by Claire
      Almeras].

PMID- 15869026
TI  - [Warning about overconsumption of psychotropic drugs in adolescents].

PMID- 15869027
TI  - [Alternating residence, what challenges?].

PMID- 15869028
TI  - [The child with vision disorders. Multidisciplinary management].

PMID- 15869029
TI  - [Principal causes of vision disorders in children].

PMID- 15869030
TI  - [Integration of the visually handicapped child and legislation].

PMID- 15869031
TI  - [Orthoptic management of the visually impaired child].

PMID- 15869032
TI  - [Psychological mechanisms in the visually handicapped child].

PMID- 15869033
TI  - [Mainstreaming the visually handicapped child into daycare].

PMID- 15869034
TI  - [The missions of the Family Support Service and Early Education].

PMID- 15869035
TI  - [History and modernization of the Braille system].

PMID- 15869036
TI  - [Ethics in pediatric nursing, respect for decision making].

PMID- 15869037
TI  - Forcible medication and personal autonomy: the case of Charles Thomas Sell.

PMID- 15869038
TI  - Liquorice and hypertension.
AB  - Glycyrrhetinic acid, the active constituent of liquorice, inhibits renal IIbeta
      hydroxysteroid dehydrogenase. This allows cortisol to stimulate mineralocorticoid
      receptors, which can result in hypertension and hypokalaemia. Treatment options
      are based on pathophysiological understanding.

PMID- 15869039
TI  - Anti-IgE and other new immunomodulation-based therapies for allergic asthma.
AB  - Understanding of the cellular and molecular mechanisms in asthma has lead to the
      recognition of a number of potential therapeutic targets, a few of which have
      been evaluated in clinical studies. Parenteral administrations of both anti-IL-5
      and IL-12 inhibit eosinophil recruitment to the airways, but display a lack of
      clinical efficacy. Interrupting the IL-4 pathway thus far has also shown
      disappointing results in clinical studies. Omalizumab is the first anti-IgE
      monoclonal antibody developed for the treatment of moderate to severe asthmatics
      to receive FDA approval. In a number of clinical trials treatment with omalizumab
      was associated with moderate improvements in a number of relevant endpoints,
      including the rate of occurrence of disease exacerbations. Newer DNA-based
      therapeutic strategies including DNA vaccination and the antisense
      oligonucleotides show promise but thus far have only been tested in animal
      models.

PMID- 15869040
TI  - Is chronic HIV infection associated with venous thrombotic disease? A systematic
      review.
AB  - Infection with the human immunodeficiency virus (HIV) is still a major health
      problem world-wide. HIV infection has changed into a chronic infection with the
      chance of developing long-term complications. Vascular complications are
      frequently reported in the current literature. HIV and treatment by highly active
      antiretroviral therapy (HAART) are associated with many cardiovascular risk
      factors. An increased risk of arterial cardiovascular complications was found in
      a number of studies. However, data about the risk of venous thrombotic disease
      (VTE), including potentially fatal conditions as pulmonary embolism, were
      limited. In a systematic review of the literature, ten relevant epidemiological
      studies were identified that investigated the risk of venous thrombotic disease
      in HIV-infected patients. The incidence was increased two- to tenfold in
      comparison with a healthy population of the same age. However, these studies were
      mainly retrospective cohort studies that were prone to selection bias,
      confounding factors were not always mentioned and in all but three control
      populations were missing. An increased risk of venous thrombotic disease in HIV
      infected patients could be explained by the presence of a hypercoagulable state,
      characterised by an increase in procoagulant factors, such as endothelial TF
      expression and thrombogenic properties of microparticles, and a decrease in
      anticoagulant factors, including AT III, HC II and the protein C pathway.
      Furthermore, the risk of VTE was associated with an increased risk of infections
      and autoimmune haemolytic anaemia, and was weakly associated with HAART. All
      together, quite some evidence pointed towards a relationship between HIV
      infection and venous thrombotic disease, but the association still needs to be
      established in properly designed epidemiological studies.

PMID- 15869041
TI  - Microscopic colitis: prevalence and distribution throughout the colon in patients
      with chronic diarrhoea.
AB  - BACKGROUND: Microscopic colitis presents with chronic diarrhoea with or without
      abdominal pain. Microscopic colitis is an important cause of chronic diarrhoea.
      It can be distributed throughout the colon, as well as limited to the right
      colon. Microscopic colitis is associated with coeliac disease. We studied the
      prevalence and distribution of microscopic colitis in patients with diarrhoea and
      normal colonoscopy and we studied the association with coeliac disease. METHODS:
      Colonoscopy was performed. Biopsies were taken from every segment of the colon.
      Lymphocytic colitis was defined as the presence of more than 20 lymphocytes per
      100 epithelial cells and collagenous colitis was defined as thickening of the
      basal membrane of more than 10 microm. Upper endoscopy was performed if upper
      intestinal symptoms were present. If this was the case, small bowel biopsies were
      taken. RESULTS: Microscopic colitis was found in 13 out of 103 patients. The
      distribution was diffuse throughout the colon in ten and restricted to the right
      colon in three patients. In seven patients, upper endoscopy was performed. Marsh
      I/II lesions were found in six out of seven patients. CONCLUSION: Microscopic
      colitis was limited to the right colon in 23% of patients. Biopsies of
      macroscopically normal colonic mucosa in patients with diarrhoea is mandatory.

PMID- 15869042
TI  - The importance of corpus biopsies for the determination of Helicobacter pylori
      infection.
AB  - BACKGROUND: The aim of this study was to determine whether an antral biopsy alone
      represents an adequate tissue sample to diagnose the presence of Helicobacter
      pylori on the mucosa. Furthermore, we explored the conditions associated with the
      presence of H. pylori in the corpus. METHODS: Consecutive patients who underwent
      an upper gastrointestinal endoscopy at a single centre between January 1995 and
      May 1997 were studied. Biopsies were taken at each endoscopy to assess the
      presence of H. pylori: two antral and two corpus biopsies for histological
      examination and one antral and one corpus biopsy for the CLO test. RESULTS: A
      total of 620 patients underwent an upper gastrointestinal endoscopy, 307 (50%)
      were H. pylori infected. In 80% of the endoscopies there was total agreement
      between the performed biopsy tests. The addition of corpus biopsies increases the
      diagnostic yield by 10% in H. pylori-positive patients. Patients with only corpus
      infection more often showed atrophy and intestinal metaplasia compared with
      patients with both antral and corpus infection, 37 vs 20%, respectively (OR 2.2,
      95% CI 1.1-4.4). CONCLUSION: One biopsy from the antrum or corpus seems to be
      inadequate to diagnose the presence of H. pylori on the mucosa. Patients with an
      infection exclusively in the corpus more often had worse mucosa pathology.

PMID- 15869043
TI  - Severe hypokalaemic paralysis and rhabdomyolysis due to ingestion of liquorice.
AB  - Chronic ingestion of liquorice induces a syndrome with findings similar to those
      in primary hyperaldosteronism. We describe a patient who, with a plasma K+ of 1.8
      mmol/l, showed a paralysis and severe rhabdomyolysis after the habitual
      consumption of natural liquorice. Liquorice has become widely available as a
      flavouring agent in foods and drugs. It is important for physicians to keep
      liquorice consumption in mind as a cause for hypokalaemic paralysis and
      rhabdomyolysis.

PMID- 15869044
TI  - The old lady who liked liquorice: hypertension due to chronic intoxication in a
      memory-impaired patient.
AB  - The authors report an 85-year-old patient admitted because of cognitive
      impairment. During examination hypertension and hypokalaemia were found. After
      some time it was discovered that the patient was eating too much liquorice. The
      case demonstrates that liquorice intoxication should be considered as a cause of
      hypertension in old age. Furthermore the case demonstrates that missing an
      intoxication is a pitfall for medical history taking of patients with cognitive
      impairment.

PMID- 15869045
TI  - A diagnosis not to be missed. Small intestinal ischaemia.

PMID- 15869046
TI  - Pneumococcal polysaccharide vaccines.

PMID- 15869047
TI  - Is aspirin resistance a risk factor?

PMID- 15869048
TI  - Carvedilol's antiarrhythmic properties: therapeutic implications in patients with
      left ventricular dysfunction.
AB  - Carvedilol is a beta- and alpha-adrenergic-blocking drug with clinically
      important antiarrhythmic properties. It possesses anti-ischemic and antioxidant
      activity and inhibits a number of cationic channels in the cardiomyocyte,
      including the HERG-associated potassium channel, the L-type calcium channel, and
      the rapid-depolarizing sodium channel. The electrophysiologic properties of
      carvedilol include moderate prolongation of action potential duration and
      effective refractory period; slowing of atrioventricular conduction; and reducing
      the dispersion of refractoriness. Experimentally, carvedilol reduces complex and
      repetitive ventricular ectopy induced by ischemia and reperfusion. In patients,
      carvedilol is effective in controlling the ventricular rate response in atrial
      fibrillation (AF), with and without digitalis, and is useful in maintaining sinus
      rhythm after cardioversion, with and without amiodarone. In patients with AF and
      heart failure (HF), carvedilol reduces mortality risk and improves left
      ventricular (LV) function. Large-scale clinical trials have demonstrated that
      combined carvedilol and angiotensin-converting enzyme inhibitor therapy
      significantly reduces sudden cardiac death, mortality, and ventricular arrhythmia
      in patients with LV dysfunction (LVD) due to chronic HF or following myocardial
      infarction (MI). Despite intensive neurohormonal blockade, mortality rates remain
      relatively high in patients with post-MI and nonischemic LVD. Recent trials of
      implantable cardioverter-defibrillators added to pharmacologic therapy,
      especially beta blockers, have shown a further reduction in arrhythmic deaths in
      these patients.

PMID- 15869049
TI  - Thoughts about the ventricular gradient and its current clinical use (Part I of
      II).
AB  - The concept of the ventricular gradient was conceived in the mind of Frank Wilson
      in the early 1930s. Wilson, a mathematical genius, believed that the calculation
      of the ventricular gradient yielded information that was not otherwise
      obtainable. The method of analysis was not utilized by clinicians at large
      because the concept was not easy to understand and because the method used to
      compute the direction of the ventricular gradient was so time consuming that
      clinicians could not use it. Grant utilized the concept to create vector
      electrocardiography, but he believed that if his method of analysis was used, it
      was not often necessary to compute the direction of the ventricular gradient. He
      did, however, describe an easy way to compute the direction of the ventricular
      gradient. The current major clinical use of the ventricular gradient is to
      identify primary and secondary T-wave abnormalities in an electrocardiogram
      showing left or right ventricular hypertrophy or left or right ventricular
      conduction abnormalities. In addition, the author uses the term ventricular time
      gradient instead of ventricular gradient in an effort to clarify the concept.
      Finally, the author discusses the possible clinical significance of a normally
      directed but shorter than normal ventricular time gradient, an attribute that has
      not been emphasized previously.

PMID- 15869050
TI  - Peripheral levels of matrix metalloproteinase-9, interleukin-6, and C-reactive
      protein are elevated in patients with acute coronary syndromes: correlations with
      serum troponin I.
AB  - BACKGROUND: Acute coronary syndromes (ACS) are characterized by activation of
      systemic and local inflammatory mediators. The interrelation between these
      soluble inflammatory markers and their association with markers of myocardial
      necrosis have not been extensively studied. HYPOTHESIS: The study was undertaken
      to evaluate the association of the systemic levels of matrix metalloproteinase-9
      (MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), with C-reactive
      protein (CRP), interleukin-6 (IL-6), and serum troponin-I in patients admitted
      with ACS. METHODS: Analysis of serum concentrations of the above inflammatory
      markers was performed in 53 patients with unstable angina (UA) and in 15 with non
      ST-segment elevation myocardial infarction (NSTEMI) within 48 h of admission, and
      34 patients with stable coronary artery disease. RESULTS: Compared with patients
      with stable angina, those with ACS had elevated admission levels of MMP-9 (p =
      0.04), CRP (p < 0.001), and IL-6 (p = 0.001), but not TIMP-1 (p = 0.55). Compared
      with patients with UA, those with NSTEMI also had higher levels of IL-6 (p <
      0.001), CRP (p = 0.002), and MMP-9 (p = 0.05). CONCLUSIONS: In patients with ACS,
      the admission levels of inflammatory mediators, including MMP-9, CRP, and IL-6
      are significantly elevated, specifically in association with serum troponin I.
      Systemic and local markers of inflammatory activity may be directly associated
      with myocardial injury.

PMID- 15869051
TI  - Images in cardiology: Giant left atrial aneurysm secondary to mitral stenosis.

PMID- 15869052
TI  - Images in cardiology: Hypereosinophilic syndrome and effect of imatinib mesylate.

PMID- 15869053
TI  - Continuous 12-lead electrocardiographic ST monitoring adds prognostic information
      to the thrombolysis in myocardial infarction risk score in patients with non-ST
      elevation acute coronary syndromes.
AB  - BACKGROUND: Continuous 12-lead electrocardiographic (ECG) ST monitoring and the
      Thrombolysis In Myocardial Infarction Risk Score (TIMI-RS), both have been shown
      to be useful for early risk stratification in patients with non-ST elevation
      acute coronary syndromes (NSTACS). HYPOTHESIS: Transient ST ischemic events,
      detected by continuous 12-lead ECG ST monitoring, early in the course of NSTACS,
      may add prognostic information to the TIMI-RS. METHODS: In all, 567 consecutive
      patients with a NSTACS underwent 24-h continuous 12-lead ECG ST monitoring. An ST
      ischemic event was defined as a transient ST shift in any lead of > or = 0.10 mV
      compared with the reference ECG, lasting for > or = 1 min. RESULTS: The incidence
      of the composite of death, nonfatal myocardial infarction (or reinfarction) and
      recurrent ischemia by Day 14 was 22.2%. By Day 30, the incidence of the composite
      of death and nonfatal myocardial infarction (or reinfarction) was 14.7%. There
      was a significantly increased risk of 14-day (p value for trend < 0.001) or 30
      day (p value for trend <0.001) composite endpoint with increasing of TIMI-RS.
      Moreover, the occurrence of > or = 1 ST shifts during ST monitoring was
      associated with a significantly increased risk of 14- (p value < 0.001) or 30-day
      (p value < 0.001) composite endpoint, and this was true throughout the groups of
      TIMI-RS. CONCLUSIONS: The present study suggests that continuous 12-lead ECG ST
      monitoring, early in the course of NSTACS, may serve as an affordable tool to add
      prognostic information to the TIMI-RS.

PMID- 15869054
TI  - Interleukin-1 receptor antagonist levels correlate with extent of myocardial loss
      in patients with acute myocardial infarction.
AB  - BACKGROUND: Interleukin-1 receptor antagonist (IL-1Ra) levels are elevated early
      in patients with acute myocardial infarction (MI) and often precede release of
      markers of necrosis; however, IL-1Ra levels did not correlate previously with
      infarct size and prognosis in such patients. HYPOTHESIS: The goal of our study
      was to evaluate prospectively the correlation between IL-1Ra levels upon
      emergency department (ED) presentation and the extent of myocardial necrosis and
      prognosis in patients with ST-segment elevation MI. METHODS: Levels of IL-1Ra
      were measured upon ED presentation in 44 consecutive patients (40 men, aged 55 +/
      10 years). Peak values of creatine kinase (CK) and CK-MB were determined during
      hospitalization, and left ventricular ejection fraction (LVEF) was evaluated by
      echocardiography before discharge. All patients were followed prospectively and
      underwent clinical and echocardiographic assessment at 42 +/- 3 months after the
      infarction. RESULTS: Levels of IL-1Ra upon ED presentation correlated directly
      with CK (p = 0.002) and CK-MB (p = 0.01) peak levels and correlated inversely
      with LVEF before discharge (p = 0.009). Patients with in-hospital adverse events
      had significantly higher IL-1Ra levels upon ED admission (n = 10,2620 +/- 4706
      pg/ml) than those without events (n = 34,598 +/- 457 pg/ml) (p = 0.015).
      CONCLUSIONS: In patients with MI, levels of IL-1Ra upon ED presentation
      correlated significantly with the extent of myocardial necrosis, as measured by
      cardiac enzymes peak and reduction of LVEF, and are predictive of in-hospital
      events. Results of this study may influence early therapeutic approach in
      patients with acute MI.

PMID- 15869055
TI  - Study on changes of heme oxygenase-1 expression in patients with coronary heart
      disease.
AB  - BACKGROUND: Heme oxygenase (HO) is a rate-limiting enzyme of endogenetic carbon
      monoxide (CO) that degrades heme into carbon monoxide, bilirubin, and iron. These
      products have important physiologic effects: bilirubin is a potent antioxidant
      that can act against ischemia/reperfusion injury; there is a negative correlation
      between the content of HO-1 and the incidence of coronary heart disease (CHD).
      HYPOTHESIS: This study was undertaken to investigate the changes of HO-1 in
      patients with CHD. METHODS: Thirty-five patients with acute myocardial infarction
      (AMI), 40 patients with unstable angina pectoris (UAP, diagnosed by coronary
      angiography), and 30 patients with stable angina pectoris (AP, diagnosed by
      coronary angiography) were selected for the study; another 30 patients with
      normal coronary artery (diagnosed by coronary angiography) were selected as
      controls. The levels of HO-1 protein expression in monocyte and lymphocyte in the
      subjects were tested by immunohistochemistry and western blot. Computer picture
      analyzing systems were also used to measure the levels of HO-1 protein
      expression. RESULTS: Heme oxygenase-1 protein is located in cell plasma. The
      levels of HO-1 protein expression in patients with CHD were significantly higher
      than in those without CHD (p < 0.01). There were significant differences of HO-1
      expression among the three groups of patients with CHD. The group with AMI was
      the highest, followed by the group with UAP and finally by the group with AP.
      CONCLUSIONS: There is a higher expression of HO-1 in patients with CHD. The
      levels of HO-1 protein are associated with the severity of CHD.

PMID- 15869056
TI  - Images in cardiology: Right ventricular rupture.

PMID- 15869057
TI  - Long-term efficacy and stability of atrial sensing in VDD pacing.
AB  - BACKGROUND: The efficacy and stability of atrial electrode sensing function is
      essential in maintaining atrioventricular (AV) synchrony and activity response in
      VDD pacing. Studies to evaluate the relationship between atrial sensing efficacy,
      stability, and implantation strategy are few. HYPOTHESIS: This study sought to
      determine the possible predictors, among the recipients' underlying clinical
      conditions and the implantation strategies used, of achieving the most stable and
      effective atrial sensing. METHODS: Eighty consecutive adults implanted with VDD
      pacemakers were studied retrospectively. Atrial electrodes were positioned where
      the optimal atrial potentials (APs) were measured during implantation.
      Interrogation parameters, including AV-synchrony ratio, were acquired immediately
      post implantation, at 1 year, and at 2 years after pacemaker implantation.
      Appropriate atrial sensing efficacy was defined as AV-synchrony ratio > or = 90%.
      The stability of atrial sensing was evaluated by the variation ranges of measured
      APs. RESULTS: The measured APs showed no statistical difference when age, gender,
      or comorbidity was considered. However, with pacing-lead bending angles < or = 90
      degrees, patients may have presented with larger APs and narrower AP variation
      than patients with obtuse angles. There were no clinical parameters in our study
      that could have predicted the proper atrial sensing efficacy with an AV-synchrony
      ratio > or = 90%. CONCLUSIONS: The long-term sensing efficacy and stability of
      VDD pacing is reliable. More sophisticated implantation strategies may further
      improve the atrial sensing stability and efficacy in VDD pacing.

PMID- 15869058
TI  - Charles P. Bailey.

PMID- 15869059
TI  - Is it time to introduce varicella vaccination?

PMID- 15869060
TI  - The role of calprotectin in the diagnosis of neonatal necrotising enterocolitis.

PMID- 15869061
TI  - Unplanned out of hospital births--who delivers the babies?
AB  - We report on 14 cases of unplanned out of hospital deliveries which occurring
      over a three year period. The incidence was 0.31%. All th women were booked and
      multi-parous. 11 (79%) of 14 deliveries occurred between the hours of 20.00 and
      0800, suggesting some difficulty in getting to the hospital or a reluctance to
      attend the hospital during these hours. Family members were responsible for the
      deliveries in 7 (50%) of cases, and there was no maternal or fetal mortality.
      Morbidity in the babies was mainly hypothermia which occurred in 7 (50%) of the
      babies, 2 of whom (14%) required admission to the special care baby unit while 2
      (14%) of the mothers suffered second degree tears. We conclude that women and
      their partners should be educated about contingency planning regarding how to
      respond in situations of unplanned out of hospital deliveries, to minimize
      maternal and neonatal morbidity.

PMID- 15869062
TI  - Experience of hepatitis C among current or former heroin users attending general
      practice.
AB  - The majority of injecting drug users in Ireland are infected with hepatitis C
      (HCV) and many attend general practice for methadone maintenance treatment. To
      describe awareness and experience of HCV infection, related investigations and
      treatment, a semi-qualitative interview study of current or former heroin users
      attending a general practice was carried out. Twenty-five patients (69% of total)
      were interviewed, of whom 23 were on methadone maintenance therapy at the time of
      the interview and 22 were HCV positive. While awareness of harm reduction
      measures and health implications of the infection was good, continued high-risk
      activity was common. Negative experiences at diagnosis, of subsequent
      investigations and treatments received were common. Only one person had been
      treated for HCV. We conclude there are a number of barriers to effective HCV
      management among heroin users and further research is needed to improve our
      understanding of this issue.

PMID- 15869063
TI  - Pubovaginal sling for urodynamic stress incontinence: effect on patient quality
      of life.
AB  - To report the medium term effects of the pubovaginal sling (PVS) on patient
      quality of life (QOL). Patients and Methods Over a two year period, 72 females
      aged between 17 and 63 years (mean 46.1 years) underwent PVS for urodynamic
      stress incontinence (USI). All data were accrued prospectively. Preoperative
      assessment consisted of a full history (including King's Health and SF-36
      questionnaires), physical examination, urinalysis and urodynamics.
      Postoperatively all patients were assessed at 6 weeks and 6 months. At these
      intervals each patient was questioned regarding persistence or recurrence of USI,
      presence of urge/urge incontinence (UI) and QOL. Preoperatively, 60 patients
      (83.3%) demonstrated type II USI and 12 (16.7%) had type III USI. Detrusor
      overactivity (DO) was also present in 3 patients. At 6 weeks 100% of patients
      remained completely dry, 8 (11%) patients complained of urgency but none
      complained of UI. At 6 months 95% of the subjects remained dry, 3 complained of
      recurrent USI, 7 complained of urgency and 1 of UI. The incidence of de novo
      urgency was 5.5%. There were significant improvements in 4 of the 8 domains of
      the SF-36, and in 8 of the 9 domains of the King's Health questionnaire, at both
      6 weeks and 6 months follow-up. PVS is effective in the treatment of all types of
      USI, with early success rates of up to 95%. The procedure is associated with
      minimal morbidity and has a positive impact on patient QOL.

PMID- 15869064
TI  - Cost effective prescribing of proton pump inhibitors (PPI's) in the GMS Scheme.
AB  - Total expenditure under the Community Drugs Schemes in Ireland on the proton pump
      inhibitors (PPI's) used for the management of patients with dyspepsia was
      approximately 64 million Euro in 2002, an 8-fold increase since 1995. As PPI
      maintenance therapy accounts for the majority of this expenditure we determined
      potential cost savings to the GMS scheme should the prescribing of these drugs
      for maintenance therapy follow published clinical and cost effectiveness
      guidelines. Substitution, in accordance with therapeutic indication, of the PPI
      with the greatest individual cost i.e. omeprazole (Losec Mups) with any of the
      alternative agents particularly the generic omeprazole preparations Ulcid &
      Lopraz, rabeprazole (Pariet) and pantoprazole (Protium) would be expected to
      produce cost savings in excess of 5 million Euro per annum. These savings may be
      further enhanced by increasing the step down from healing to maintenance doses of
      these drugs.

PMID- 15869065
TI  - The implementation of a nurse-provided, ward-based bilevel non-invasive
      ventilation service.
AB  - Bilevel non-invasive ventilation (NIV) is now standard of care for patients with
      acute hypercapnic respiratory failure (AHRF), and has an increasing role to play
      in patients with stable chronic hypercapnic respiratory failure (CHRF). The
      institution of an NIV service in a hospital setting requires major
      infrastructural and multidisciplinary input to be effective. This paper describes
      our experiences in setting up a 24-hour, nurse-provided, ward-based NIV service
      in a new acute teaching hospital in Dublin over a 39-month period. In addition,
      we provide audit data on 78 patients with AHRF treated with NIV by this service
      over this time period. The majority of patients (65) had their respiratory
      acidosis corrected and were discharged home; 11 patients failed NIV and were
      intubated and mechanically ventilated in the ITU; 13 patients died, 8 from
      respiratory causes and 5 from non-respiratory causes, indicating the critical
      nature of this condition.

PMID- 15869066
TI  - Play-wrestlers and their injuries.
AB  - Television (TV) broadcast wrestling series have become very popular amongst Irish
      children in recent years. Over a four-month study period, 2.3% of injuries seen
      at a busy paediatric fracture clinic were attributable to play-wrestling. The
      mean age was 9.5 years (range 4-15 years). All of the children had been role
      playing wrestlers and imitating wrestling "moves" seen on TV. None had formal
      training in wrestling or martial arts. The commonest injury was fracture of the
      distal radius (7/13). One child required general anaesthetic for manipulation of
      a dorsally displaced fracture of radius. All other injuries were treated
      conservatively and resolved without sequelae.

PMID- 15869067
TI  - Percutaneous stenting of the superior vena cava syndrome in a patient with cystic
      fibrosis.
AB  - Superior vena cava (SVC) obstruction commonly occurs in the setting of
      malignancy. Cases of benign SVC obstruction are being seen more frequently with
      the use of long-term central venous lines. This is the case particularly in
      Cystic Fibrosis (CF). We describe in this report the successful use of
      intravascular stenting to treat this distressing condition in the setting of
      thrombotic occlusion of the SVC in a patient with CF.

PMID- 15869068
TI  - Universal neonatal hearing screening.

PMID- 15869069
TI  - Eisenmenger's syndrome in a 27 week pregnancy--management with bosentan and
      sildenafil.

PMID- 15869070
TI  - An unusual cause of abdominal pain.

PMID- 15869071
TI  - Early intervention with spinal cord stimulation in the management of a chronic
      regional pain syndrome.

PMID- 15869072
TI  - Spotlight on teenage pregnancy.

PMID- 15869073
TI  - Smoking among young people in the MWHB Region in 1997 and 2002.

PMID- 15869074
TI  - Saturday night cornea.

PMID- 15869075
TI  - Developing our emergency mental health research capacity: taming the chaos in a
      multidisciplinary field.

PMID- 15869076
TI  - Understanding terror networks.

PMID- 15869078
TI  - Cultural diversity in the integration of disaster mental health and public
      health: a case study in response to bioterrorism.
AB  - Disaster leads to severe disruptions of the coping capacities of the community.
      Terrorism, and in particular bioterrorism, has tremendous impact on the community
      that is affected Cultural groups present unique issues that need to be
      appreciated for the effective integration of disaster mental health services with
      public health. The following paper identifies unique issues and challenges of
      cultural groups in disaster. It highlights issues such as language, cultural
      interpretation and expression of grief, and help-seeking behavior, as well as
      inherent cultural resources that can promote resilience. The implications of
      these cultural issues are illustrated in a potential bioterrorist event,
      addressing the areas of surge capacity, mass quarantine, and risk communication.
      Next steps are identified in promoting greater cultural competency in the
      integration of disaster mental health and public health, thus building greater
      community resilience.

PMID- 15869079
TI  - Emergency response service personnel and the critical incident stress debriefing
      debate.
AB  - Previous research has demonstrated the potential for work-related stress
      associated with employment in the emergency service field. However, little
      research has considered effective interventions that may be used to mediate the
      effects of this work-related stress. Critical Incident Stress Debriefing (CISD)
      is one intervention that is currently employed with emergency service workers.
      However, the efficacy of this intervention is currently the source of much
      debate. The present discussion reviews the available literature regarding the
      effectiveness of CISD for use with emergency service workers and concludes that
      at this time, for this population, the call for the removal of current programs
      using CISD is unwarranted.

PMID- 15869077
TI  - A prospective cohort study of the effectiveness of employer-sponsored crisis
      interventions after a major disaster.
AB  - Postdisaster crisis interventions have been viewed by many as the appropriate and
      immediate approach to enhance psychological well-being among persons affected by
      large-scale traumatic events. Yet, studies and systematic reviews have challenged
      the effectiveness of these efforts. This article provides the first rigorous
      scientific evidence to suggest that postdisaster crisis interventions in the
      workplace significantly reduced mental health disorders and symptoms up to 2
      years after the initial interventions. Until now, studies have neither focused on
      the effectiveness and safety of brief mental health services following disasters,
      or traumatic events generally, nor examined the long-term impact of these
      interventions across a spectrum of outcomes using a rigorous research design. The
      focus of this study was to examine the impact of brief mental health crisis
      interventions received at the worksite following the World Trade Center disaster
      (WTCD) among a random sample of New York adults. The data for the present study
      come from a prospective cohort study of 1,681 adults interviewed by telephone at
      1 year and 2 years after this event. Results indicate that worksite crisis
      interventions offered by employers following the WTCD had a beneficial impact
      across a spectrum of outcomes, including reduced risks for binge drinking,
      alcohol dependence, PTSD symptoms, major depression, somatization, anxiety, and
      global impairment, compared with individuals who did not receive these
      interventions. In addition, it appeared that 2-3 brief sessions achieved the
      maximum benefit for most outcomes examined. Implications for postdisaster crisis
      interventions efforts are discussed.

PMID- 15869080
TI  - Critical incident stress management for persons residing in institutions.
AB  - Critical Incident Stress Management (CISM) approaches have proven themselves to
      be effective in mitigating the stress and anxiety that are often found in at-risk
      populations in the aftermath of traumatic incidents. A frequently overlooked
      group of persons at risk are those individuals who reside in a variety of
      institutions. Extensive research spanning a half century has shown these
      individuals to have heightened sensitivity to anxiety in general and traumatic
      events in particular. CISM approaches would appear to hold promise in assisting
      with these residents' needs. This paper outlines a basic CISM approach that could
      be adopted and adapted by a variety of institutional settings for the special
      needs of their residents. Preincident, acute care, and postincident response
      initiatives are presented, and the implications for such program development are
      discussed.

PMID- 15869081
TI  - The impact of an exercise program on posttraumatic stress disorder, anxiety, and
      depression.
AB  - This preliminary study assessed the impact of a 12-session aerobic exercise
      program on symptoms of Posttraumatic Stress Disorder (PTSD), anxiety, and
      depression. Overall results show no symptom reduction during baseline phases but
      significant reductions in PTSD, anxiety, and depression following the exercise
      intervention. Reductions were maintained during a 1 month follow-up. Results
      suggest that exercise programs may be valuable resources for managing treatment
      resistant participants with PTSD and may also have a beneficial effect on anxiety
      and depression.

PMID- 15869082
TI  - Adding a doctor? Ask these questions.

PMID- 15869083
TI  - Who sent me Mrs. Mottira?

PMID- 15869084
TI  - How I connect with patients.

PMID- 15869085
TI  - Where does drug importation stand now?

PMID- 15869086
TI  - What are these doctors doing right?

PMID- 15869087
TI  - Updating patient information.

PMID- 15869088
TI  - When patients complain.

PMID- 15869089
TI  - Why I'm a plaintiffs' expert.

PMID- 15869090
TI  - Our voice.

PMID- 15869091
TI  - Dr. Gershen's writing continues to inspire.

PMID- 15869092
TI  - Dr. Gershen's writing continues to inspire.

PMID- 15869093
TI  - Dr. Gershen's writing continues to inspire.

PMID- 15869094
TI  - Kudos for a wonderful fall issue.

PMID- 15869095
TI  - Kudos for a wonderful fall issue.

PMID- 15869096
TI  - Medicine's Balancing Act.

PMID- 15869097
TI  - Members speak out on House Bill 2.

PMID- 15869099
TI  - Members speak out on House Bill 2.

PMID- 15869098
TI  - Members speak out on House Bill 2.

PMID- 15869100
TI  - Gene therapy and stem cell research.

PMID- 15869101
TI  - A short primer on stem cells.

PMID- 15869102
TI  - The politics of vaccine production.

PMID- 15869103
TI  - Wyeth Pharmaceutical's perspective on vaccine production.

PMID- 15869104
TI  - Influence and drug marketing.

PMID- 15869105
TI  - Orphan drugs provide needed treatment options.

PMID- 15869107
TI  - Goats, satyrs, and fauns.

PMID- 15869106
TI  - Human infections with avian influenza viruses.
AB  - Avian influenza A viruses are zoonotic agents that can cause outbreaks of acute
      respiratory disease in animals and man. The unprecedented re-emergence of highly
      pathogenic H5N1 influenza viruses in the human population has resulted in the
      deaths of 42 people and slaughter of millions of birds in Asia. The most striking
      features of this virus are its ability to infect and cause disease in a wide
      range of animals and to spread from person to person. There are also instances of
      infections with H7 and H9 subtypes in humans that are not discussed in this
      article. Therefore it is crucial to develop virologic surveillance programs for
      animal and human influenza, to limit the spread of the virus from infected
      poultry, and to develop efficacious vaccines by exploiting novel technologies
      such as reverse genetics.

PMID- 15869108
TI  - 2004 - 05 influenza vaccine shortage.

PMID- 15869109
TI  - House Bill 2 is first step toward additional tort reform.

PMID- 15869110
TI  - The career of the mentally ill: an integration of psychiatric, labeling/social
      construction, and lay perspectives.
AB  - This paper provides a new way of conceptualizing the career of the mentally ill.
      Most persons who experience an episode of a serious mental disturbance lead a
      normal life, while a few persons lead lifetimes that revolve around their mental
      disorders. The processes leading to either result can only be understood by
      integrating the traditional labeling and psychiatric perspectives with lay
      understandings of the concepts of "mental illness" and "nervous breakdowns." A
      selection of key concepts from these perspectives leads to a better understanding
      of the different paths persons take as they move through the pre-patient,
      inpatient, and post-patient phases of the "career of the mentally ill." This
      perspective makes understandable a number of counterintuitive relationships. For
      example, it explains why most hospitalized mental patients (1) have a negative
      stereotype of the "mentally ill," (2) do not perceive themselves as "mentally
      ill, yet (3) perceive themselves as benefiting from treatment, and (4) do not
      progress into a career of secondary deviance.

PMID- 15869111
TI  - Is it really worse to have public health insurance than to have no insurance at
      all? Health insurance and adult health in the United States.
AB  - Using prospective cohort data from the 1979 National Longitudinal Survey of
      Youth, this study examines the extent to which health insurance coverage and the
      source of that coverage affect adult health. While previous research has shown
      that privately insured nonelderly individuals enjoy better health outcomes than
      their uninsured counterparts, the same relationship does not hold for those
      publicly insured through programs such as Medicaid. Because it is unclear whether
      this finding reflects a true causal relationship or is in fact due to selection
      bias on socioeconomic status and health, previous estimates of the contribution
      of health insurance to inequities in health may have been biased. This study
      attempts to disentangle these competing hypotheses of causation or selection bias
      by using fixed effects models with sibling clusters to corroborate--or contradict
      -the results of a conventional OLS regression. By controlling for unobserved
      factors shared by siblings, such as parental genetic influences, sibling models
      estimate health insurance effects that are less affected by selection bias.
      Findings suggest that, among the US. birth cohorts of 1957 to 1961, the negative
      relationship between public health insurance and health is not causal, but rather
      due to prior health and socioeconomic status. Conversely, the lack of health
      insurance coverage has a strong cumulative negative impact on adult health.

PMID- 15869112
TI  - Body mass index, academic achievement, and school context: examining the
      educational experiences of adolescents at risk of obesity.
AB  - Reflected self-appraisal suggests that individual functioning is related to the
      fit between individual characteristics and the norms of their primary contexts.
      To apply this social psychological concept to the study of obesity, we
      hypothesized that adolescents at risk of obesity would have lower academic
      achievement overall than other students, especially in schools in which their
      weight status was most likely to elicit negative evaluations. Multi-level
      modeling of nationally representative data revealed that the negative
      longitudinal association between risk of obesity and achievement was stronger in
      schools with higher rates of romantic activity and lower average body size among
      students, two school contexts in which obesity was likely to be stigmatized, but
      weaker in schools with higher rates of athletic participation, a school context
      in which such stigmatization was also likely. Additional analyses suggested that
      this last, unexpected finding reflected a process of niche-picking.

PMID- 15869113
TI  - School and county characteristics as predictors of school rates of drug, alcohol,
      and tobacco offenses.
AB  - Despite evidence that school factors are associated with differences in various
      types of student behavior, little research has explored the predictive utility of
      school factors for school-level substance offense rates. Using data from the
      State of Florida Department of Education and the Census, we explore the
      associations between school climate and school substance offense rates,
      controlling for county level characteristics. Results from a multilevel analysis
      show that school culture, school organization, and social milieu predict
      variation in school substance incident rate. We interpret the findings as
      consistent with research utilizing the "school culture/school effectiveness"
      model.

PMID- 15869114
TI  - When caregiving ends: the course of depressive symptoms after bereavement.
AB  - This study describes depressive symptoms among caregivers following bereavement
      and connects these trajectories to earlier features of caregiving using life
      course and stress process theory. Data are from a six-wave longitudinal survey
      (five years) of spouses and adult children caring for someone with Alzheimer's
      Disease. The analytic subsample (N = 291) is defined by death of the care
      recipient after the baseline interview. A latent class mixture model is used to
      identify distinctive clusters of depressive symptoms over time. Of the four
      trajectories identified, three represent stable symptom levels over time, with
      two-thirds being repeatedly symptomatic (medium symptom levels), compared to two
      smaller groups of repeatedly asymptomatic (effectively absent of symptoms) and
      repeatedly distressed (severe symptoms). In contrast, about one in five
      caregivers experiences improved emotional well-being over time, the temporarily
      distressed, who progress from severe to moderate symptom levels. Caregivers with
      few symptoms before bereavement tend to maintain these states afterwards, but
      emotionally distressed caregivers tend to become more distressed. Role overload
      before bereavement substantially increases the odds of following an unfavorable
      trajectory afterwards, whereas self-esteem and socioemotional support play
      protective roles. These results demonstrate that caregivers are not uniform in
      their emotional responses to bereavement, but follow several distinct
      trajectories. These trajectories are linked to their previous experiences as
      caregivers, in particular exposure to stressors and access to resources. These
      findings suggest that intervention during caregiving may facilitate adaptation
      following death of a loved one.

PMID- 15869115
TI  - Self-rated health and mortality: does the relationship extend to a low income
      setting?
AB  - Although a relationship between poor self-reported health status and excess
      mortality risk has been well-established for industrialized countries, almost no
      research considers developing countries. We use data from Indonesia to show that
      in a low-income setting, as in more advantaged parts of the world, individuals
      who perceive their health to be poor are significantly more likely to die in
      subsequent follow-up periods than their counterparts who view their health as
      good. This result characterizes both men and women, holds for multiple time
      periods, and remains after inclusion of measures of nutritional status, physical
      functioning, symptoms of poor physical health and depression, and hypertension.
      We also consider the correlates of self-rated health. Symptoms and physical
      functioning are strong predictors of reporting poor rather than good health, but
      neither these indicators nor other covariates we consider distinguish between
      reports of excellent rather than good health.

PMID- 15869116
TI  - Disability identity and attitudes toward cure in a sample of disabled activists.
AB  - This study investigates the assumption that disabled people want improvements in
      their functional abilities, or complete cures. Contrary to this assumption, many
      disabled activists are found to have attitudes in which they refuse treatment
      that promises a cure. In order to explain this attitude, different sources of
      disability identity are isolated as potential predictor variables. A multivariate
      model reveals that self-identity related to a personal affirmation of disability
      is a significant predictor of refusal of treatment, as is the age of onset of
      disability. Implications for interactions with medical professionals and utility
      based modeling of medical treatment seeking are discussed.

PMID- 15869117
TI  - The shifting engines of medicalization.
AB  - Social scientists and other analysts have written about medicalization since at
      least the 1970s. Most of these studies depict the medical profession,
      interprofessional or organizational contests, or social movements and interest
      groups as the prime movers toward medicalization. This article contends that
      changes in medicine in the past two decades are altering the medicalization
      process. Using several case examples, I argue that three major changes in medical
      knowledge and organization have engendered an important shift in the engines that
      drive medicalization: biotechnology (especially the pharmaceutical industry and
      genetics), consumers, and managed care. Doctors are still gatekeepers for medical
      treatment, but their role has become more subordinate in the expansion or
      contraction of medicalization. Medicalization is now more driven by commercial
      and market interests than by professional claims-makers. The definitional center
      of medicalization remains constant, but the availability of new pharmaceutical
      and potential genetic treatments are increasingly drivers for new medical
      categories. This requires a shift in the sociological focus examining
      medicalization for the twenty-first century.

PMID- 15869118
TI  - Neighborhood socioeconomic disadvantage and access to health care.
AB  - Most research on access to health care focuses on individual-level determinants
      such as income and insurance coverage. The role of community-level factors in
      helping or hindering individuals in obtaining needed care, however, has not
      received much attention. We address this gap in the literature by examining how
      neighborhood socioeconomic disadvantage is associated with access to health care.
      We find that living in disadvantaged neighborhoods reduces the likelihood of
      having a usual source of care and of obtaining recommended preventive services,
      while it increases the likelihood of having unmet medical need. These
      associations are not explained by the supply of health care providers.
      Furthermore, though controlling for individual-level characteristics reduces the
      association between neighborhood disadvantage and access to health care, a
      significant association remains. This suggests that when individuals who are
      disadvantaged are concentrated into specific areas, disadvantage becomes an
      "emergent characteristic " of those areas that predicts the ability of residents
      to obtain health care.

PMID- 15869119
TI  - Age at first birth, health, and mortality.
AB  - The biodevelopmental view sees the readiness and soundness of the organism at the
      time of first birth as its prime link to health and survival years and decades
      later. It suggests an optimum age at first birth shortly after puberty. The
      biosocial view emphasizes social correlates and consequences of age at first
      birth that may influence health and survival many years later. It suggests that
      better health and survival come from delaying motherhood as long as possible,
      perhaps indefinitely. Analyses consistently find patterns more in keeping with
      the biosocial view in a U.S. national sample of women ages 25 through 95. The
      fitted curves show high levels of current health problems among women who first
      gave birth in or shortly after puberty. Problems drop steadily the longer that
      first birth was delayed, up to about age 34, then rise increasingly steeply,
      particularly after about age 40. For women currently of the same age, the ratio
      of health problems expected given first birth under age 18 versus around age 34
      equals that from currently being 14 years older. Health problems rise steeply
      with length of having delayed beyond age 40. Mortality hazard also declines with
      having delayed first birth well beyond the end of puberty. The ratio of mortality
      hazard between mothers with teenage versus late first births equals that from a
      10-year difference in current age. Comparison to nonmothers of similar age and
      race/ethnicity shows that the correlation of motherhood with health problems and
      mortality hazard switches from detrimental to beneficial with delay beyond about
      age 22.

PMID- 15869120
TI  - Health lifestyle theory and the convergence of agency and structure.
AB  - This article utilizes the agency-structure debate as a framework for constructing
      a health lifestyle theory. No such theory currently exists, yet the need for one
      is underscored by the fact that many daily lifestyle practices involve
      considerations of health outcomes. An individualist paradigm has influenced
      concepts of health lifestyles in several disciplines, but this approach neglects
      the structural dimensions of such lifestyles and has limited applicability to the
      empirical world. The direction of this article is to present a theory of health
      lifestyles that includes considerations of both agency and structure, with an
      emphasis upon restoring structure to its appropriate position. The article begins
      by defining agency and structure, followed by presentation of a health lifestyle
      model and the theoretical and empirical studies that support it.

PMID- 15869121
TI  - Volunteering and depression in later life: social benefit or selection processes?
AB  - Does volunteer participation reduce depressive symptoms among older people? Does
      depression influence whether older people will volunteer? Might nonrandom
      attrition in a longitudinal study bias the relationship between volunteering and
      depression? This research addresses these questions with three-wave data from
      theAmericans' Changing Lives study. Multigroup structural equation models for
      complete and incomplete data are used to estimate the joint causal relationship
      between volunteer work and depression. The results reveal a beneficial effect of
      formal volunteering on depression, but not for informal helping. Depression was
      shown to be associated with a subsequent increase in formal volunteering,
      suggesting voluntarism as a means of compensation. Functional health problems,
      not depression, emerged as the important barrier to volunteering. In addition, a
      sample selection effect--depressed persons and nonvolunteers were less likely to
      complete the panel study--was detected and accounted for in the analysis. The
      results are discussed in light of the legitimacy of formal social integration.

PMID- 15869122
TI  - Anger in black and white: race, alienation, and anger.
AB  - Using data from the 1996 General Social Survey and the 1973 Chicago Crowding
      Study, we test the hypotheses that African Americans feel and express more anger
      than whites, that sense of control (versus powerlessness) lessens anger and
      mistrust increases anger, and that these indicators of alienation affect anger
      differently for African Americans and whites. We find that when age and gender
      are controlled, African Americans neither feel nor express more anger than
      whites, despite having a lower average sense of control and higher mistrust. This
      is partly because the effects of sense of control and mistrust on anger differ by
      race. Sense of control reduces feelings of anger and anger expression more for
      African Americans than whites. Mistrust increases feelings of anger for whites,
      but not African Americans. The results provide further evidence that, in the
      stress process, social structural location may moderate the effects of
      "detriments" and "resources" on emotional upset.

PMID- 15869123
TI  - Differential labeling of mental illness by social status: a new look at an old
      problem.
AB  - Whether the higher rates of mental hospitalization and involuntary treatment for
      marginal social groups are due to differential labeling or simply to the
      occurrence of higher rates of disorder in these groups remains unresolved. I
      reexamine this issue with data from the National Comorbidity Survey (N = 5,877)
      that allow comparisons between disturbed individuals living in the community
      untreated and disturbed persons who have been hospitalized or seen a professional
      for their mental health problems under pressure or voluntarily. Contrary to
      labeling theory, members of lower status groups are not consistently
      overrepresented among those who have been hospitalized or seen a professional
      against their will. Consistent with self-labeling theory, persons with greater
      education and those not in poverty are disproportionately present among
      individuals who sought treatment by choice. Additional analyses show that factors
      that predict service utilization are important determinants of mental health
      service use but do not account systematically for status disparities in hospital
      or outpatient treatment, especially disparities by poverty status. Although I do
      not confirm a central tenet of labeling theory here, the negative consequences of
      labeling and stigma continue to be well-supported in the literature.

PMID- 15869124
TI  - The validity and reliability of maternal recall of breastfeeding practice.
AB  - In large epidemiologic studies, information on breastfeeding practice is often
      collected from maternal recall through interviews, but there is concern about the
      accuracy of the data, especially when mothers are asked to recall their practices
      from many years earlier. This review examines the validity and reliability of
      maternal recall of breastfeeding history using 11 studies published between 1966
      and 2003 in English with a sample of 10 or more. Validity is the degree to which
      recall compares with a validation standard or reference, and reliability refers
      to the degree to which the breastfeeding practices obtained by recall are
      repeatable over time. The existing studies suggest that maternal recall is a
      valid and reliable estimate of breastfeeding initiation and duration, especially
      when the duration of breastfeeding is recalled after a short period (< or = 3
      years). Validity and reliability of maternal recall for the age at introduction
      of food and fluids other than breast milk are less satisfactory. Further and more
      extensive studies on maternal recall of breastfeeding history and ways to improve
      such recall are warranted.

PMID- 15869125
TI  - Vitamin K and sphingolipid metabolism: evidence to date.
AB  - The brain is enriched with sphingolipids, which are important membrane
      constituents and major lipid signaling molecules that have a role in motor and
      cognitive behavior. Vitamin K has been implicated in brain sphingolipid
      metabolism for more than 30 years. The in vitro and in vivo studies to date
      suggest a role of vitamin K in the regulation of multiple enzymes involved in
      sphingolipid metabolism within the myelin-rich regions in the brain. However, the
      precise mechanisms of action are not well understood. Further, the physiological
      consequences of the observed effects of vitamin K on sphingolipid metabolism have
      not been systematically studied.

PMID- 15869126
TI  - Zinc supplementation: neuroprotective or neurotoxic?
AB  - While zinc is essential for normal brain function and repair, recent work has
      implicated this trace element in the neuronal damage and death that follow
      traumatic brain injury, stroke, and seizure. Therefore, the development of new
      zinc-based therapeutic strategies will need to consider the emerging roles of
      zinc in the central nervous system.

PMID- 15869127
TI  - Role of diet in blood glucose response and related health outcomes: summary of a
      meeting.
AB  - Consumption of foods that elicit a marked glycemic response have been proposed as
      risk factors for obesity and insulin resistance. A group of experts from around
      the world participated in a discussion of scientific issues about the role of
      diet in blood glucose response and related health outcomes. The goal was to
      determine how diet can best be used to prevent rather than to treat disease. This
      was an informed discussion rather than a formal, evidence-based review. To
      resolve debate on this topic, well-controlled research with healthy individuals
      is needed.

PMID- 15869128
TI  - The economic impact of early enteral feeding in gastrointestinal surgery: a
      prospective survey of 51 consecutive patients.
AB  - Early postoperative oral feeding has been demonstrated to be safe and not
      increase postoperative morbidity. There are conflicting reports about its effect
      on postoperative length of stay. Some patients will fail attempts at early
      postoperative feeding and may be relegated to a longer postoperative course. Few
      studies to date have attempted to identify cost savings associated with early
      oral support, and those identified address nasoenteric support only. Fifty-one
      consecutive patients were randomized into either a traditional postoperative
      feeding group or an early postoperative feeding group after their
      gastrointestinal surgery. Length of hospital stay, hospital costs (excluding
      operating room costs), morbidity, and time to tolerance of a diet were compared.
      There was a tendency toward increased nasogastric tube use in the early feeding
      arm, but the morbidity rates were similar. Length of hospital stay and costs were
      similar in both arms. Early postoperative enteral support does not reduce
      hospital stay, nursing workload, or costs. It may come at a cost of higher
      nasogastric tube use, however, without an increase in postoperative morbidity.

PMID- 15869129
TI  - Myofibrosarcoma of the adrenal gland.
AB  - Adrenal masses have varying presentations. Most commonly, adrenal masses are
      discovered incidentally on CT or MRI during an evaluation for an unrelated
      complaint. Although the majority of these are nonfunctional cortical adenomas,
      hormonally active tumors and adrenocortical carcinoma must also be considered in
      the differential diagnosis. Rarely, retroperitoneal tumors may mimic an adrenal
      mass. We report a case of a 49-year-old man with anemia and weight loss who was
      found to have a large retroperitoneal mass arising from the adrenal gland.
      Surgical treatment involved en bloc resection of the right kidney, adrenal gland,
      segments 7 and 8 of the liver, and a portion of the right hemidiaphragm. Final
      pathology revealed a low-grade myofibrosarcoma. We believe that this is the first
      case report of a myofibrosarcoma of the adrenal gland. Myofibrosarcomas are rare
      malignant tumors composed of myofibroblasts that arise from the deep soft
      tissues. These tumors have a predilection for the head and neck, trunk, or
      extremities. Myofibrosarcomas can be differentiated from other sarcomas by
      immunohistochemical staining and pathologic features. We will briefly discuss the
      workup of an adrenal mass and focus on the diagnosis of myofibrosarcoma.

PMID- 15869130
TI  - In the wake of Hurricane Isabel: a prospective study of postevent trauma and
      injury control strategies.
AB  - Preventing hurricane-related injuries (HRI) has historically centered on the pre
      event and event phases of the disaster. To date, no study has focused on injuries
      occurring during the postevent phase. We examined HRI that occurred after
      Hurricane Isabel struck a U.S. urban city. HRI presenting 1 week prior to the
      hurricane were collected from emergency department electronic records. HRI that
      presented to our level 1 trauma center were prospectively collected for 1 week
      after the hurricane. Nine hundred seventy-eight patients with possible HRI were
      identified. Fifty-one patients with trauma directly attributed to the hurricane
      were used for analysis. The number of HRI occurring before, during, and after the
      hurricane were 7 (14%), 3 (6%), and 41 (80%), respectively. The majority of HRI
      (37%) occurred on posthurricane day 1. Head, chest, upper and lower extremities
      accounted for 9 (18%), 8 (16%), 13 (26%), and 14 (28%) of HRI. More than one
      third of HRI patients were admitted to the hospital, and 12 (24%) underwent an
      operation. The average hospital length of stay was 4.7 days. Of our trauma
      alerts, 75 per cent had an Injury Severity Score (ISS) >8, and 20 per cent had an
      ISS >15. Tree-related injuries (TRI) accounted for 59 per cent of HRI. Males,
      ages 50-60, had the highest incidence of injury (63%). Significant injuries occur
      in the wake of a hurricane. Optimization of disaster preparation must include
      prevention strategies targeted to the postevent recovery phase of disasters.

PMID- 15869131
TI  - Treatment and outcomes of melanoma with a Breslow's depth greater than or equal
      to one millimeter in a regional teaching hospital.
AB  - Local control and regional lymph node evaluation are the primary treatment goals
      for cutaneous primary melanoma. Historically, primary lesions were excised with
      large 3- to 5-cm radial margins. Recent clinical trials have suggested that
      similar survival and recurrence rates can be achieved with smaller margins of
      excision. In addition to excision of the primary lesion, the presence or absence
      of nodal metastasis is the single most powerful predictor of survival in patients
      with melanoma. Based on the available trials, the standard of care for a melanoma
      1 mm or greater in depth is a wide local excision with a 2-cm margin and a
      sentinel lymph node biopsy (SLNB). The application of this standard in regional
      teaching hospitals is unknown. We performed a retrospective review of a cancer
      registry at a teaching hospital in South Carolina. This analysis included all
      patients who underwent surgery for melanoma at our institution between July 1997
      and March 2003. Our single inclusion criterion was that the primary melanoma had
      to be 1 mm or greater in depth. Only 42 per cent of the patients underwent
      excision with a radial margin >2 cm, and only 60 per cent of the patients
      underwent SLNB. As time progressed, the use of SLNB at our institution increased;
      but, even as late as 2003, some patients did not receive SLNB. Adherence to
      standards did not appear to have an effect on overall survival. In conclusion,
      the current standard for the treatment of invasive melanoma greater than or equal
      to 1 mm in thickness is a 2-cm margin of excision and a SLNB. In this regional
      teaching hospital, surgical treatment and staging of melanoma did not strictly
      adhere to the standard.

PMID- 15869132
TI  - A proposed algorithm for managing the open abdomen.
AB  - Delayed abdominal closure has gained acceptance in managing a variety of surgical
      conditions. Multiple techniques were devised to promote safe, uncomplicated,
      expeditious fascial closure. We retrospectively reviewed patient records between
      September 22, 2001 and June 30, 2004. Of the 20 patients with open abdomen, two
      patients died within 24 hours and one was transferred. The remaining 17 were
      managed using an algorithm including a combination of delayed primary closure
      (DPC), vacuum-assisted fascial closure (VAFC), Wittmann Patch (WP) (Star
      Surgical, Inc., Burlington, WI), and planned ventral hernia via absorbable mesh
      with split thickness skin grafting (PVH). The mean Simplified Acute Physiology
      Scores (SAPS II) was 31 (predicted mortality 73%). All patients initially
      underwent VAFC and re-exploration 12-48 hours later. Indications for continued
      VAFC included 1) gross contamination, 2) massive bowel edema, 3) continued
      bleeding at re-exploration. If these conditions were absent, DPC was attempted or
      a WP was employed until fascial closure. Twenty-eight day mortality was 5.9 per
      cent (1/17 patients). Enterocutaneous fistulae occurred in two patients (11.7%).
      Fascial closure was achieved in 6 patients (35.3%). Eleven patients were managed
      with PVH. Using an algorithm with a combination of several techniques, open
      abdomen can be managed with minimal morbidity and acceptable closure rates.

PMID- 15869133
TI  - Diverticular abscess presenting as an incarcerated inguinal hernia.
AB  - Acute diverticulitis may present with an abscess that is usually pericolonic or
      pelvic and can be treated with urgent surgery or percutaneous drainage. We
      present a case of a diverticular abscess presenting as a left inguinal hernia.
      This is analogous to an Amyand's hernia in which an inflamed appendix is found in
      a right inguinal hernia. The patient presented was managed with open drainage of
      the hernia and subsequent laparoscopic sigmoid resection in the same
      hospitalization.

PMID- 15869134
TI  - A burn mass casualty event due to boiler room explosion on a cruise ship:
      preparedness and outcomes.
AB  - The purpose of this study was to review our experience with a mass casualty
      incident resulting from a boiler room steam explosion aboard a cruise ship.
      Experience with major, moderate, and minor burns, steam inhalation, mass casualty
      response systems, and psychological sequelae will be discussed. Fifteen cruise
      ship employees were brought to the burn center after a boiler room explosion on a
      cruise ship. Eleven were triaged to the trauma resuscitation area and four to the
      surgical emergency room. Seven patients were intubated for respiratory distress
      or airway protection. Six patients had >80 per cent burns with steam inhalation,
      and all of these died. One of the 6 patients had 99 per cent burns with steam
      inhalation and died after withdrawal of support within the first several hours.
      All patients with major burns required escharotomy on arrival to trauma
      resuscitation. One patient died in the operating room, despite decompression by
      laparotomy for abdominal compartment syndrome and pericardiotomy via thoracotomy
      for cardiac tamponade. Four patients required crystalloid, 20,000 mls/m2-27,000
      ml/m2 body surface area (BSA) in the first 48 hours to maintain blood pressure
      and urine output. Three of these four patients subsequently developed abdominal
      compartment syndrome and died in the first few days. The fourth patient of this
      group died after 26 days due to sepsis. Five patients had 13-20 per cent bums and
      four patients had less than 10 per cent burns. Two of the patients with 20 per
      cent burns developed edema of the vocal cords with mild hoarseness. They improved
      and recovered without intubation. The facility was prepared for the mass casualty
      event; having just completed a mass casualty drill several days earlier. Twenty
      six beds were made available in 50 minutes for anticipated casualties. Fifteen
      physicians reported immediately to the trauma resuscitation area to assist in
      initial stabilization. The event occurred at shift change; thus, adequate support
      personnel were instantaneously to hand. Our mass casualty preparation proved
      useful in managing this event. Most of the patients who survived showed signs of
      post-traumatic stress syndrome, which was diagnosed and treated by the burn
      center psychology team. Despite our efforts at treating large burns (>80%) with
      steam inhalation, mortality was 100 per cent. Fluid requirements far exceeded
      those predicted by the Parkland (Baxter) formula. Abdominal compartment syndrome
      proved to be a significant complication of this fluid resuscitation. A
      coordinated effort by the facility and preparation for mass casualty events are
      needed to respond to such events.

PMID- 15869135
TI  - Percutaneous endoscopic transgastric jejunostomy: a new approach.
AB  - A percutaneous transgastric jejunostomy allows long-term simultaneous gastric
      decompression and jejunal feedings. We have developed a safe and effective
      bedside technique for placement of a large-bore (22 French) feeding tube while
      providing gastric drainage with no mortalities and minimal morbidities. We have
      modified the push technique used for percutaneous gastrostomies and introduced a
      cut-away sheath that is placed using a modified Seldinger technique. The entire
      procedure is performed under endoscopic visualization. Our experience with more
      than 100 successful tube placements has made this method common practice at our
      institute. This technique is ideal for patients with poor gastric emptying of any
      etiology. We feel that this technique will have an expanding and important role
      in the future management of this patient population's nutritional problems.

PMID- 15869136
TI  - Surgical complications and causes of death in trauma patients that require
      temporary abdominal closure.
AB  - Temporary abdominal closure (TAC) has increasingly been employed in the
      management of severely injured patients to avoid abdominal compartment syndrome
      (ACS) and as part of damage control surgery (DCS). Although the use of TAC has
      received great interest, few data exist describing the morbidity and mortality
      associated with its use in trauma victims. The main goal of this study is to
      describe the incidence of surgical complications following the use of TAC as well
      as to define the mortality associated with this procedure. A retrospective review
      of patients admitted to a state-designated level 1 trauma center from April 2000
      to February 2003 was performed. Inclusion criteria were age >18 years, traumatic
      injury, and need for exploratory laparotomy and use of TAC. A total of 120
      patients were included in the study. The overall mortality of trauma patients
      requiring TAC was 59.2 per cent. The most common causes of death were acute
      inflammatory process (50.7%), followed by hypovolemic shock (43.7%). The
      incidence of surgical complications was 26.6 per cent. Intra-abdominal abscesses
      were the most frequent surgical complication (10%). After multiple logistic
      regression analysis, increasing age and a numerically greater initial base
      deficit were found to be independent predictors of mortality in trauma patients
      that require TAC.

PMID- 15869137
TI  - Importance of identifying the course of the recurrent laryngeal nerve in total
      and near-total thyroid lobectomies.
AB  - In our clinic, near-total thyroidectomy is the principal surgical procedure
      performed for benign thyroid diseases. We conducted a single-institution study on
      176 consecutive patients who underwent near-total thyroidectomy due to various
      thyroid diseases. We compared the incidence of recurrent laryngeal nerve injury
      between total and near-total thyroid lobectomy sides in each patient. Our
      hypothesis was that the incidence of recurrent laryngeal nerve injury after total
      thyroid lobectomy would be similar to that of near-total thyroid lobectomy when
      the course of the recurrent laryngeal nerve was identified during surgery. The
      temporary recurrent laryngeal nerve palsy rates on the total and near-total
      thyroid lobectomy sides were 3.9 per cent (7 of 176 nerves) and 2.2 per cent (4
      of 176 nerves), respectively. The difference was not statistically significant.
      Permanent recurrent laryngeal nerve palsy did not occur in any of our patients.
      In conclusion, the incidence of recurrent laryngeal nerve injury in total versus
      near-total thyroid lobectomy is not different when the course of the recurrent
      laryngeal nerve is identified during surgery.

PMID- 15869138
TI  - A fatal case of necrotizing fasciitis caused by Serratia marcescens.
AB  - A patient with a history of type II diabetes mellitus (DM), end stage renal
      disease (ESRD), and congestive heart failure (CHF) developed necrotizing
      fasciitis caused by Serratia marcescens after scraping his leg on rocks in a
      river while fishing. Aggressive management with surgical debridement,
      antibiotics, and pressure support was unsuccessful.

PMID- 15869139
TI  - Small bowel ischemia after Roux-en-Y gastric bypass complicated by pregnancy: a
      case report.
AB  - Small bowel obstruction is an unusual complication of pregnancy. Its occurrence
      after Roux-en-Y gastric bypass (RYGB) for morbid obesity complicated by pregnancy
      is rare. Morbid obesity describes body weight at least 100 lb over the ideal
      weight, or a body mass index (BMI) > or = 40. Surgery offers the only viable
      treatment option with long-term weight loss and maintenance. This case report
      involves a 23-year-old female at 25 weeks gestation with a 1-day history of
      diffuse abdominal pain and vomiting. She had a RYGB with a 15 cc micropouch 6
      months prior to the commencement of this pregnancy. All radiologic investigations
      were normal. Esophagogastroscopy was performed revealing an ischemic Roux limb of
      the gastric bypass. At laparotomy, an internal hernia involving the afferent limb
      was identified at the site of the Roux anastomosis compromising portions of both
      the afferent and Roux limbs. Nonviable portions of both the afferent and Roux
      limbs were resected. Gastrointestinal continuity was achieved by fashioning a
      gastro-gastrostomy and a jejuno-jejunostomy, thus reversing the original gastric
      bypass procedure. The immediate postoperative period was complicated by fetal
      demise. With the increase in bariatric surgery, small bowel ischemia after Roux
      en-Y gastric bypass will most likely become more prevalent, particularly in women
      of childbearing age.

PMID- 15869140
TI  - Significance of the effective remnant liver volume in major hepatectomies.
AB  - The aim of this study is to identify the minimum safe amount of effective remnant
      liver volume (ERLV) in patients undergoing a major hepatectomy. Thirty-eight
      consecutive major hepatectomies (resection of > or = 3 Couinaud segments)
      performed between July 1999 and March 2004 in which a frozen section liver biopsy
      was obtained were included. No patient had chronic viral hepatitis, cirrhosis, or
      cholestasis. The total liver volume (TLV) was calculated using the Vauthey
      formula, and the postsurgical liver volume (PSLV) was derived by subtracting the
      estimated volume of liver resected from the TLV. The PSLV minus the percentage of
      macrovesicular steatosis as nonfunctional liver was defined as the effective
      remnant liver volume (ERLV). Three groups of ERLV/TLV ratios (<30%, between 30%
      and 60%, and >60%) were correlated with liver resection type, mortality,
      complications, intraoperative blood transfusions, operative time, length of
      hospitalization, and mean value of liver function tests in the first 5
      postoperative days. Comparisons between clinical parameters were performed by
      Pearson chi2 test. There was significant correlation between ERLV/TLV ratios and
      surgical resection type (P < 0.001), early postoperative mortality (P < 0.01),
      and complications (P < 0.003). The ERLV/TLV ratio may be a useful predictor of
      surgical outcome after major hepatectomy.

PMID- 15869141
TI  - Complete androgen insensitivity syndrome: the role of the endocrine surgeon.
AB  - Androgen insensitivity syndrome (AIS) is an X-linked recessive disorder
      characterized by varying degrees of feminization secondary to androgen receptor
      insensitivity. We report a case of a 34-year-old female with complete androgen
      insensitivity who presented with a history of primary amenorrhea and two intra
      abdominal gonads found on CT scan. The patient underwent successful laparoscopic
      bilateral gonadectomy without complications. AIS is present in 1:20,000 to 64,000
      males; complete androgen insensitivity is seen in 2-5:100,000 phenotypic females
      and should therefore be considered in any otherwise healthy female with abnormal
      pubertal development and infertility. Although controversial, most
      endocrinologists agree that gonadectomy may be performed after puberty with
      minimal risk of testicular neoplasm.

PMID- 15869142
TI  - Role of repeat computerized tomography in nonoperative management of solid organ
      trauma.
AB  - Nonoperative management (NOM) of blunt spleen and liver trauma is currently well
      accepted. CT imaging is helpful in selecting treatment options and to evaluate
      resolution of solid organ trauma. This 8-year study was undertaken to assess the
      role of repeat CT scans in NOM by analyzing indications of surgery in NOM
      failures. NOM was undertaken in 221 patients with spleen/liver trauma. After
      initial CT scans, 82 (37%) scans were repeated in 65 patients. There was failure
      of NOM (NOMF) in 11 patients. Follow-up imaging was done prior to delayed surgery
      in 4 (36%) patients, 4.9 per cent of repeat scans. Two of these patients had
      hemodynamic instability and, in the other two, there were clinical signs of
      peritonitis. The remaining seven patients had delayed surgery due to hemodynamic
      instability. There is a limited role of repeat CT scans in NOM of spleen and
      liver trauma. Repeat CT should be done more liberally in patients with suspected
      intestinal and mesenteric trauma, unexplained blood loss, complex hepato-biliary
      trauma, and in patients with neurological or pharmacological paralysis.

PMID- 15869143
TI  - Delayed rupture of a left ventricular aneurysm after blunt trauma.
AB  - We report a case where a 17-year-old male involved in a motor vehicle crash was
      admitted after seemingly minor blunt chest trauma. The patient was discharged the
      following day without complications. He was subsequently found dead 45 days later
      from a ruptured traumatic left ventricular aneurysm. We review briefly the
      epidemiology of patients with this complication and also suggest that the optimal
      method and timing of following and identifying discharged patients at risk for
      this rare but devastating complication is still unclear based on current
      literature.

PMID- 15869145
TI  - Chilaiditi's syndrome: what should every surgeon know?
AB  - Demetrius Chilaiditi first described an incidental radiological finding of
      hepatodiaphragmatic interposition of bowel in 1910. The condition could be
      mistaken for pneumoperitoneum. This radiographic entity, known as Chilaiditi's
      sign, is found in asymptomatic patients and must be distinguished from
      Chilaiditi's syndrome, which produces symptomatology associated with the bowel
      interposition. A review of the literature yielded 27 published cases of
      Chilaiditi's syndrome. These cases were compiled to evaluate various aspects of
      this rare but important entity.

PMID- 15869144
TI  - Splanchnic hypoperfusion-directed therapies in trauma: a prospective, randomized
      trial.
AB  - Splanchnic hypoperfusion as reflected by gastric intramucosal acidosis has been
      recognized as an important determinant of outcome in shock. A comprehensive
      splanchnic hypoperfusion-ischemia reperfusion (IRP) protocol was evaluated
      against conventional shock management protocols in critical trauma patients. The
      study was a prospective randomized trial comparing three therapeutic approaches
      to hypoperfusion after severe trauma in 151 trauma patients admitted to the
      intensive care unit. Group 1 patients received hemodynamic support based on
      conventional indicators of hypoperfusion. In group 2, resuscitation was further
      guided by gastric tonometry-derived estimates of splanchnic hypoperfusion and
      included more invasive hemodynamic monitoring and additional administration of
      colloid or crystalloid solutions, or inotropic support. Group 3 patients
      additionally received therapies specifically aimed at. optimizing splanchnic
      perfusion and minimizing oxidant-mediated damage from reperfusion. The three
      groups were similar based on age, Injury Severity Score, and Acute Physiology and
      Chronic Health Evaluation II Scores. There were no statistically significant
      differences in mortality rates, organ dysfunction, ventilator days, or length of
      stay between any of the interventions. Techniques of optimization of splanchnic
      perfusion and minimization of oxidant-mediated reperfusion injury evaluated in
      this study were not advantageous relative to standard resuscitation measures
      guided by conventional or tonometric measures of hypoperfusion in the therapy of
      occult and clinical shock in trauma patients.

PMID- 15869146
TI  - Occult fifth gland intrathyroid parathyroid adenoma identified by gamma probe.
AB  - We report the case of a 54-year-old woman undergoing radioguided
      parathyroidectomy in whom four normal glands were identified on cervical
      exploration. The gamma probe was instrumental in guiding us to the adenoma in a
      fifth gland that was not visible and was localized to the parenchyma of the left
      lobe of the thyroid gland. Many surgeons do not advocate use of the gamma probe
      in minimally invasive parathyroidectomy and rely solely on focused exploration on
      the basis of a preoperative sestamibi scan and intraoperative rapid parathyroid
      hormone assays. This case, however, illustrates the utility of the gamma probe in
      parathyroid adenoma localization.

PMID- 15869147
TI  - Novel technique for placement of hemodialysis catheters using a combined open
      procedure with the Seldinger micropuncture technique.
AB  - Percutaneous placement of large-diameter dialysis catheters via the Seldinger
      technique can be technically challenging in patients with coagulopathy, difficult
      anatomy, or several previous central line insertions. We describe a method for
      achieving safer access by combining an open approach to delineate the venous
      anatomy of the chest wall, with a micropuncture device and smaller diameter
      guidewire to gain intravascular access to the cephalic vein or its major
      tributaries. Serial dilation of otherwise unusable vessels can then permit
      successful and safer hemodialysis catheter insertion in these difficult cases.

PMID- 15869148
TI  - Benign anatomical mistakes: "ampulla of Vater" and "papilla of Vater".
AB  - The anatomy of the ampullary termination of the bile and pancreatic ducts is
      complex; appropriate terminology for this area is confusing and inaccurate. We
      examine the terms "ampulla of Vater" and "papilla of Vater" for anatomical and
      historical correctness. The term "ampulla" refers to a dilated part of a duct or
      other channel. Thus, this word is topographically correct to describe the
      dilatation at the confluence of the bile and main pancreatic ducts; historically,
      however, there is considerable reason to believe that its first description was
      by Santorini rather than Vater. The eponymous term "papilla of Vater" is also
      incorrect historically. The use of eponyms is firmly entrenched in the medical
      literature, but some are so problematic that they should be discarded. The
      eponymous terms for both the ampulla and the papilla should be replaced with the
      terms "hepatopancreatic ampulla" (or "biliaropancreatic ampulla") and "major [or
      "greater"] duodenal papilla," respectively.

PMID- 15869149
TI  - "Most brilliant in judgment": Alexander the Great and Aristotle.
AB  - From historical sources, it is evident that Alexander the Great was indebted to
      one of his teachers, Aristotle of Stagira. It was the teaching of Aristotle that
      evoked all the nascent talents of young Alexander and turned him into a great
      man. Alexander was extremely interested in the secrets of medicine and considered
      it an art. The medical knowledge he acquired from Aristotle may have saved his
      life and the lives of his troops on many occasions. If Alexander did not possess
      medical knowledge and if his everyday life had not been so greatly influenced by
      medicine, he might never have been able to create his empire.

PMID- 15869150
TI  - Magnetic resonance imaging findings in spinal cord infarction in three small
      breed dogs.
AB  - Fibrocartilaginous embolization (FCE) of the spinal cord is a common disease in
      large breed dogs. There are only a few reports about this entity in small breed
      dogs and it has never been reported in chondrodystrophic breed. For definitive
      diagnosis histopathologic examination is necessary. Magnetic resonance imaging
      (MRI) as a potential diagnostic tool for intravitam diagnosis of FCE has been
      mentioned before, but results have not been reported so far. This report
      describes the neurological findings and MRI results in three small breed dogs,
      including a Pekingese dog, with FCE of the spinal cord. The disease was suspected
      in two animals based upon clinical and MRI-appearance and confirmed in the third
      by histopathological examination. In all three cases, similar focal
      intramedullary lesions, consisting of hyperintensive signals on T2-weighted
      images, were detected. Based on these findings, high-field MRI may be used as an
      antemortem tool for the diagnosis of FCE. It is also shown that FCE can occur in
      chondrodystrophic dogs.

PMID- 15869151
TI  - Endoscopic retrograde cholangio-pancreatography in healthy Beagles.
AB  - Endoscopic retrograde cholangiography and pancreatography was performed in seven
      healthy Beagles to assess the common bile duct and the accessory pancreatic duct
      after retrograde filling with an iodine contrast medium. All dogs had a major and
      a minor duodenal papilla. One Beagle had additionally an accessory papilla. The
      diameter of the contrast filled ducts was measured at three defined measure
      points (MP1-3) in ventrodorsal radiographs and left lateral radiographs. In
      ventrodorsal radiographs of endoscopic retrograde cholangiography the common bile
      duct had a straight craniomedial course. The mean duct diameter was from proximal
      to distal 3.04 +/- 1.89mm at MP1, 2.38 +/- 1.23 mm at MP2, and 2.11 +/- 0.84 mm
      at MP3. In ventrodorsal radiographs of endoscopic retrograde pancreatography, the
      left and right branch of the accessory pancreatic duct united in the pancreatic
      body. The mean diameter of the right branch was 0.88 +/- 0.14 mm at MP1, 0.72 +/-
      0.2 mm at MP2 and 0.61 +/- 0.11 mm at MP3. The left branch had a diameter of 0.93
      +/- 0.28 mm at MP1, 0.86 +/- 0.21 at MP2, and 0.6 +/- 0.07 mm at MP3. The mean
      length was 81.6 +/- 14.3 mm for the right and 107.0 +/- 24.9mm for the left
      branch. In left lateral radiographs of endoscopic retrograde pancreatography, it
      was not possible to differentiate the left from the right branch. Both branches
      ran nearly parallel and showed similar diameters but slight differences in
      length. The study proves that endosopic retrograde cholangio-pancreatography is
      possible in dogs. Radiographs taken from dogs in dorsal recumbency allow an
      objective assessment of the common bile duct and the accessory pancreatic duct.

PMID- 15869152
TI  - Variation in the lumbar spine of the mature ewe: a descriptive study.
AB  - The purpose of this descriptive study was to characterize the variation in the
      lumbar spine of the mature ewe. Ventrodorsal and lateral radiographs of the
      lumbar spine from 216 mature (4-7-year-old) Rambouillet-Columbia cross ewes were
      examined. Criteria evaluated included the number and orientation of lumbar
      vertebrae and transverse processes. Observations for fusion of the last lumbar
      vertebrae with the sacrum and any visible variability seen in transverse
      processes and ribs were also included. Forty-one percent of the mature ewes had
      six and 59% had seven lumbar vertebrae. In addition, 7% had abnormal formations
      at either the first or last lumbar vertebra. Variations seen were the first
      lumbar vertebra having one rib and one transverse process (7/216, 3%), apparent
      fusion of the last lumbar vertebra to the sacrum (5/216, 2%) or apparent fusion
      of one or both of the transverse processes of the last lumbar vertebra to the
      pelvis (2/216, 1%).

PMID- 15869153
TI  - A new type of radiographic bone remodeling in the distal radial and ulnar
      metaphysis in 54 Newfoundland dogs.
AB  - In this longitudinal observational study, 118 growing Newfoundland dogs were
      followed with sequential radiographic examination of the right front limb, which
      were scheduled at ages 3, 4, 6, 12, 18, and 24 months to record evidence of
      skeletal changes. All affected dogs had evidence of changes at 6 months and dogs
      included in this study had radiographic examination at 6 months and at least two
      other scheduled examinations that included either 4 or 12 months. The dogs were
      privately owned and had individualized nutrition and environment with no
      maintenance protocol required by the project leaders. Irregularities in bone
      remodeling in the distal radius and ulna were seen in radiographs of 54 of 118
      (45.8%) dogs. These irregularities differ from changes previously described in
      the Newfoundland dog. The reported irregularities were seen as islands of reduced
      opacity outlined by thickened, radiopaque osseous trabeculae, which were aligned
      with the axis of stress. All the 54 dogs with irregularities during some phase of
      development consistently had changes at 6 months of age. Reorganization of the
      changes in the bone was slow, and residual changes were visible at 18-24 months
      of age in many cases. The significance of these findings may lie in their
      potential for misinterpretation if they had been discovered in the presence of
      clinical signs such as any lameness or growth arrest. Radiographic appearance
      indicates disturbances in the bone maturation. The etiopathogenesis is unclear.
      Nutritional, environmental and genetic factors have to be studied.

PMID- 15869154
TI  - Use of radiography in combination with computed tomography for the assessment of
      noncardiac thoracic disease in the dog and cat.
AB  - Computed tomography (CT) of the thorax was performed in 28 dogs and five cats and
      findings were compared with previous thoracic radiographs. The sample population
      included all animals that had thoracic radiographs and a CT study within 5 days
      of each other, where the complete imaging studies were available for review.
      Thoracic radiographs were considered indeterminate in 31 patients and CT
      examinations were done to acquire additional information. The presence of
      additional information from CT relating to presence of pathology, location of
      pathology, extent of pathology, and involvement of mediastinal structures was
      recorded. Whether there was a change in diagnosis based on the CT findings was
      also recorded. In only 4/33 animals (all dogs) did CT fail to provide any new
      information for the parameters evaluated when compared with survey thoracic
      radiographs. Additional information about the pathology that was present was
      gained by CT in 5/5 cats and 21/ 28 dogs. New information on compartmental
      location of pathology was seen in 4/5 cats and 19/28 dogs. New information on
      pathology extent was noted in 5/5 cats and 20/28 dogs. Additional information
      regarding involvement of mediastinal structures was obtained in 2/5 cats and
      10/28 dogs. A change in diagnosis was made in 3/5 cats and 13/28 dogs. In
      conclusion, CT is a valuable tool for evaluating intrathoracic disease. CT
      provides additional cross-sectional anatomic information that can aid in anatomic
      localization and evaluation of the extent of the pathology in question.

PMID- 15869155
TI  - Interobserver variability of vertebral heart size measurements in dogs with
      normal and enlarged hearts.
AB  - The vertebral heart size (VHS) method by Buchanan is based on anatomic landmarks.
      A potential source of variation among observers is differences in the selection
      of measurement points. The objective was to test variability between observers
      with different levels of training in thoracic radiology and small animal clinical
      practice. Fifty sets of thoracic radiographs of cavalier King Charles spaniels,
      were divided into five groups; (Normal) normal cardiopulmonary structures, (I)
      slight cardiomegaly, (II) moderate cardiomegaly, (II +) moderate cardiomegaly
      with congestive heart failure, and (III +) severe cardiomegaly with congestive
      heart failure. Cardiomegaly was confirmed by echocardiography to be caused by
      mitral regurgitation because of myxomatous mitral valve disease. Sixteen
      observers representing four levels of experience (four observers/level) evaluated
      the radiographs; (1) European Diplomates in Veterinary Diagnostic Imaging, (2)
      Experienced small animal clinicians, (3) Trainees in small animal clinical
      practice (4) Veterinary students. Almost identical mean VHS values were found
      among the four experience levels for each of the five groups of radiographs with
      a low coefficient of variation, range 1.5-3.2%. Mean difference among the 16
      observers was 1.05 +/- 0.32 vertebrae (v). Mean difference among individuals in
      each observer group was approximately 0.5 v for all but the groups of trainees
      were the difference was 0.6-0.9 v. The conclusion is that VHS method for heart
      size is independent of observer experience but dependent of individual observers
      selection of reference points and transformation of long and short axis
      dimensions into VHS units.

PMID- 15869156
TI  - Comparison of echocardiography-guided and fluoroscopy-guided endomyocardial
      biopsy techniques.
AB  - The accuracy of bioptome placement for endomyocardial biopsy was evaluated using
      standard fluoroscopic guidance and compared simultaneously with two-dimensional
      echocardiography in six healthy subadult grizzly bears (Ursus arctos horribilis).
      Despite perceived adequate positioning of the bioptome toward the septum when
      judged using fluoroscopy, only one out of the six placements were actually
      positioned in the right ventricular apex toward the septum when evaluated using
      two-dimensional echocardiography. The bioptome was readily relocated to the right
      ventricular apex/septal location by echocardiography. The forceps were easily
      visualized at all times and the open cups were readily directed into the desired
      location for biopsy. Based on a subjective score for tissue quantity from 1 to 4
      (poor to excellent), biopsies collected by echocardiographic-guided technique had
      a mean score of 3.4, while biopsies collected by fluoroscopic-guided technique
      had a mean score of 1.8. In summary, this study suggests that endomyocardial
      biopsy locations can be accurately positioned using two-dimensional
      echocardiography with the advantages of less radiation, lower procedural costs,
      and direct visualization of the sampling site. Clear definition of endocardial
      surface as afforded by echocardiography may enhance tissue sample quality and
      lower potential complications from this procedure.

PMID- 15869157
TI  - A urinary bladder fibrosarcoma in a young dog.
AB  - A 14-month-old female dog, Gos d'Atura Catala was presented for a 7-month-history
      of reoccurring urinary tract infection. Using sonography, a focal multilobulated
      thickening of the urinary bladder wall was discovered. The solid mass was arising
      from the area of the ureteral papllDae and bulging into the lumen of the bladder
      neck. The wall of the urethra was uniformly thickened. These findings were not
      considered typical for a generalized urinary tract infection but more indicative
      of local severe inflammation, neoplasia or hyperplasia in the area of the
      ureteral openings. The thickening of the urethra was suggestive of urethritis or
      neoplastic infiltration. Signs of metastasis were not detected on the thoracic
      radiographs or in the remainder of the abdominal ultrasound examination. A
      surgical excision of the multilobulated mass was performed and histologic
      examination was conducted. A fibrosarcoma in the lamina propria of the urinary
      bladder wall was diagnosed. Because of reoccurence of hematuria and
      unresponsiveness to therapy the dog was euthanized. Postmortem examination
      confirmed the diagnosis of fiborsarcoma in the urinary bladder. Additionally,
      neoplastic infiltration of the urethral wall and metastasis in the lungs and
      liver were detected histopathologically.

PMID- 15869158
TI  - Intra- and interobserver variability of ultrasonographic measurements of the
      thyroid gland in healthy Beagles.
AB  - The repeatability of ultrasonographic measurements of the canine thyroid gland
      was evaluated. The variability of three different parameters (the maximal length,
      width, and height) within observer, between observer and between dogs was
      assessed based on three different measurements made by each of three observers
      infive healthy beagle dogs. From the three parameters, the volume of the gland
      was estimated using a formula of a rotation ellipse. The height and the volume
      had the lowest intra- and interobserver variability, while measurements of the
      length had the biggest intra- and interobserver variability. The mean values,
      with their 90% confidence interval were: height = 0.53cm [0.33-0.73], length =
      2.45cm [2.04-2.85], width = 0.62cm [0.46- 0.78], volume = 0.38 cm3 [0.20-0.55].

PMID- 15869159
TI  - Comparison of clinical, ultrasonographic, and postoperative macroscopic findings
      in cows with bursitis.
AB  - Clinical, ultrasonographic, and macroscopic findings of bursitis in cows were
      compared to assess the contribution of diagnosis and therapy planning. Sixteen
      dairy cows with swelling at the carpal (n = 12) or tarsal (n = 4) region were
      examined clinically and ultrasonographically and the findings were compared. In
      10 patients the bursae were removed in toto. According to the duration of the
      disease (history) and clinical findings nine and seven patients had acute and
      chronic bursitis, respectively. Six had fluctuation and in 10 the bursa was firm.
      Contents were serous (n = 3), serofibrinous (n = 4), serohemorrhagic (n = 2), or
      purulent (n = 1). Sonographically there was fluid in all bursa except one.
      Capsule echogenicity varied between hypoechoic and hyperechoic and mean capsule
      thickness was 9.2 +/- 4.1 mm. Fourteen of the bursae contained free-floating
      particles. The hyperechoic capsules represented fibrous tissue, and the
      echogenic/hyperechoic free-floating particles were erythrocytes, purulent
      exudate, or fibrin masses. Capsule thickness and large free-floating particles
      could not be detected by clinical examination/centesis alone. However, capsule
      thickness, bursa contents, and the extent of inflammation could be determined
      ultrasonographically and this made the decision for different invasive/ operative
      procedures easier.

PMID- 15869160
TI  - Trans-splenic portal scintigraphy in normal dogs.
AB  - The purpose of this study was to (1) establish a technique for ultrasound-guided
      trans-splenic portal scintigraphy (TSPS) using 99mTcO4(-), (2) evaluate portal
      vein morphology, (3) compare the radiation exposures for TSPS vs. per-rectal
      portal scintigraphy (PRPS), and (4) compare the quality of numerical data from
      the TSPS vs. PRPS. Eight juvenile dogs underwent PRPS and TSPS (minimum of 48h
      between studies) after initial screening tests. PRPS was done according to
      established protocol using 425 +/- 36MBq (mean +/- SD) of 99mTcO4(-). TSPS was
      done with the dogs in right lateral recumbency over the gamma camera. 99mTcO4(-)
      (57 +/- 13.9 MBq) was injected into the spleen 1-2s following initiation of the
      dynamic acquisition. The frame rate was 4 frames/s for 5 min. There was
      significantly lower radioactivity of 99mTcO4(-) given and significantly higher
      total counts recorded in the liver and heart during the TSPS compared with PRPS.
      The total counts for the TSPS and PRPS were 7120 +/- 4386 and 830 +/- 523,
      respectively. Percent absorption from the spleen was 52.5 +/- 19.1% compared with
      9.2 +/- 5.7% for the colon. Calculated transit time for the TSPS studies was 7 +/
      2.3s. In TSPS studies, the splenic and portal veins were clearly identified.
      Radiation exposure levels of the dogs were significantly lower following TSPS
      than after PRPS. TSPS appears superior to PRPS as a method to image the portal
      venous system representing a valid alternative diagnostic test for animals with
      suspected portosystemic shunts.

PMID- 15869161
TI  - Use of 99mTCO4(-) trans-splenic portal scintigraphy for diagnosis of
      portosystemic shunts in 28 dogs.
AB  - Ultrasound-guided percutaneous trans-splenic portal scintigraphy (TSPS) using
      99mTcO4(-) has been used to image the portal venous system in normal dogs.
      Compared with per-rectal portal scintigraphy, it provides higher count density,
      consistent nuclear venograms of the splenic and portal vein, and significantly
      decreased radiation exposures. This paper describes the use of TSPS for the
      diagnosis of portosystemic shunts in 28 dogs. TSPS was performed injecting 70 +/-
      28 MBq of 99mTcO4(-) (mean +/- SD) into the splenic parenchyma with ultrasound
      guidance. A dynamic acquisition at a frame rate of four frames/s for 5 min was
      initiated after placement of the needle and approximately 2s prior to injection.
      All dogs had diagnoses confirmed via exploratory laparotomy or ultrasonographic
      identification of the shunting vessel(s). Three studies (10.7%) were
      nondiagnostic because of intraperitoneal rather than intrasplenic injection of
      the radionuclide. Three pathways were recognized on the scintigraphic images: (1)
      portoazygos shunts--the 99mTcO4(-) bolus traveled dorsally, running parallel to
      the spine and entering the heart craniodorsally; (2) single portocaval or
      splenocaval shunts--the 99mTcO4(-) bolus ran from the area of the portal
      vein/splenic vein junction in a linear fashion toward the caudal vena cava
      entering the heart caudally; (3) internal thoracic shunt-the 99mTcO4 bolus
      traveled ventrally along the thorax and abdomen entering the cranial aspect of
      the heart. Single and multiple shunts were easily distinguished. There were no
      distinguishing features between single intra and extrahepatic portocaval shunts.

PMID- 15869162
TI  - A review of small animal imaging planar and pinhole spect Gamma camera imaging.
AB  - Scintigraphy (positron emission tomography (PET) or single photon emission
      computed tomography (SPECT) techniques) allows qualitative and quantitative
      measurement of physiologic processes as well as alterations secondary to various
      disease states. With the use of specific radioligands, molecular pathways and
      pharmaco-kinetic processes can be investigated. Radioligand delivery can be
      (semi)quantified in the region of interest in cross-sectional and longitudinal
      examinations, which can be performed under the same conditions or after
      physiologic or pharmacologic interventions. Most preclinical pharmacokinetic
      studies on physiological and experimentally altered physiological processes are
      performed in laboratory animals using high-resolution imaging systems. Single
      photon emission imaging has the disadvantage of decreased spatial and temporal
      resolution compared with PET. The advantage of SPECT is that equipment is
      generally more accessible and commonly used radionuclides have a longer physical
      half-life allowing for investigations over a longer time interval. This review
      will focus on single photon emission scintigraphy. An overview of contemporary
      techniques to measure biodistribution and kinetics of radiopharmaceuticals in
      small animal in vivo is presented. Theoretical as well as practical aspects of
      planar gamma camera and SPECT pinhole (PH) imaging are discussed. Current
      research is focusing on refining PH SPECT methodology, so specific regarding
      technical aspects and applications of PH SPECT will be reviewed.

PMID- 15869163
TI  - Scintigraphic evaluation of the distal tarsal region in horses with distal tarsal
      pain.
AB  - Distal tarsal pain is a common reason for hind limb lameness, but diagnosis
      cannot always be made on radiographic examination. Scintigraphy may allow
      detection of subtle changes undetected by other diagnostic methods. We
      hypothesized that (1) distal tarsal pain would be associated with a loss of the
      expected pattern of radiopharmaceutical uptake (RU) detected in normal horses,
      (2) distal tarsal RU would be greater in limbs with tarsal pain than without
      pain, (3) RU in painful tarsi with radiographic evidence of osteoarthritis (OA)
      would be greater than in distal tarsal pain with no radiographic evidence of OA.
      The study aimed to describe radiopharmaceutical distribution in the distal tarsal
      region of horses with distal tarsal pain, and to compare this with the
      contralateral limb and results from horses without tarsal pain. Retrospective
      evaluation of scintigraphic images of the distal tarsal region was performed for
      52 horses with distal tarsal pain: 15 with no radiographic evidence of OA (Group
      1) and 37 with radiographic evidence (Group 2). The images were assessed using
      vertical and horizontal profile analysis across the distal tarsal region and
      regions of interest comparisons between the distal tarsal region and tibia within
      each horse (RU ratio). Painful limbs in unilaterally lame horses from Groups 1
      and 2 had a significantly greater RU ratio than the respective contralateral
      limbs, and were significantly greater than the RU ratio in normal horses. On
      plantar images, mean region of interest counts were greater in the lame than the
      contralateral limb in Group 2 but not in Group 1. Although there was a positive
      correlation between lame and contralateral limb RU ratio in group 1, this was
      lost in group 2 horses. In lame limbs, the normal vertical activity profile was
      lost in 85% of group 1 and all of group 2, and the normal horizontal activity
      profile was lost in all of group 1 and 96% of group 2. There was a significant
      effect of lameness, but not of group on sites of peak activity on all profiles.
      The results of this study indicate that distal tarsal pain is associated with
      loss of the expected pattern of RU detected in normal horses. The findings also
      suggest that distal tarsal RU in lame limbs is greater than in limbs without
      pain, and that painful limbs with radiographic evidence of OA have a greater RU
      than painful limbs without radiographic evidence of OA.

PMID- 15869164
TI  - Play-Doh and water-soaked gauze sponges as alternative bolus material for cobalt
      60 teletherapy.
AB  - A study was performed to determine if carefully made boluses of either Play-Doh,
      or water-soaked cotton gauze sponges differed from the commercial bolus material,
      Superflab, in producing maximum radiation dose when irradiated with cobalt-60
      photons. The radiation doses were measured with thermoluminescent dosimeters
      calibrated to be accurate for cobalt-60 photon energies at doses less than 10.0
      cGy. The resulting radiation doses were similar when using Play-Doh, water-soaked
      sponges, or Superlab. Doses resulting from Play-Doh boluses more consistently
      approximated those of Superflab. The results of this study suggest that either
      Play-Doh or water-soaked cotton gauze sponges can suffice as material for
      carefully made bolus for cobalt-60 teletherapy.

PMID- 15869165
TI  - [Legionellosis in Apulia (Italy): an underevaluated disease].
AB  - The frequent occurrence of Legionnaires' disease outbreaks in many countries,
      including Italy, highlights the importance of epidemiological investigations on
      this disease. For this purpose, an active surveillance programme of pneumonia
      patients was carried out in a large hospital in Apulia (Italy) from March 2001 to
      December 2003. A total of 612 patients were tested for Legionella pneumophila
      infection by urinary antigen detection and evaluation of antibodies titre.
      Culture of respiratory specimens was performed on 117 patients. Thirty-seven
      patients (6%) tested positive for legionellosis: 10 resulted nosocomial cases and
      27 as community-acquired. Only 9 cases di Legionella pneumophila infection were
      reported from Apulia to the routine surveillance system between 1996 and 2000.
      The results of our study denote the level of underestimation of this disease in
      Apulia.

PMID- 15869166
TI  - [Epidemiologic multicenter study of the prevalence of hepatitis in hospitalised
      immigrants in Italy in the year 2002].
AB  - AIM: To retrospectively evaluate the prevalence of hepatitis in immigrant
      patients hospitalised in 48 Italian Operative Unit of Infectious Diseases during
      2002. METHODS AND PATIENTS: in our study we included the clinical data of 2255
      immigrated patients hospitalised, during the period between 01/01/2002
      31/12/2002, in ordinary admission or in Day Hospital in Infectious Diseases O.U.
      and we have evaluated the prevalence of hepatitis in this population. RESULTS:
      282 patients affected by hepatitis has been evidenced (12.5% of total
      hospitalised patients). The prevalent form was HBV-related (41.6% in chronic
      forms and 48.4% in acute), while the rate for HCV were less (37.5% in chronic and
      3% in acute). The most part of patient were men (59.6%), with a mean age of 34.2
      years and come from east-European countries (34.39%). CONCLUSION: Viral hepatitis
      are the third infectious diseases evidenced in immigrated population. HBV-chronic
      hepatitis is the prevalent form in immigrated patients, as expression of absence
      of vaccine prophylaxis in many countries. HCV-form was less frequent and it is
      particularly presents in east-European patients, probably as expression of
      endogenous drug abuse.

PMID- 15869167
TI  - [Survival of men with upper aerodigestive cancer in Umbria, Italy. 1978-82 and
      1994-98].
AB  - The aim of this study is to analyze the upper aerodigestive cancer survival in
      Umbria, a central Italian region, in the periods 1978-82 and 1994-98. The cases'
      data diagnosed in the period 1978-82 were derived from an ad hoc survey carried
      out in Umbria and for the years 1994-98 from Umbria Population-based Registry
      (RTUP). In the period 1994-98 the relative survival has lightly improved compared
      with the previous one. Comparison among five year relative standardized survival
      for head and neck, oesophagus and larynx, in Umbria region and in the other
      Italian registries, shows a quite high survival that could be further improved
      with an early diagnosis and, consequently, less destroying treatments.

PMID- 15869168
TI  - Iron deficiency anemia and feeding practices in Albanian children.
AB  - Iron deficiency is the most prevalent nutritional problem of humans. In northern
      Albania, nutritional deficiencies are widespread among children but there is a
      lack of biochemical data. The aim of this study was to assess the prevalence rate
      of the iron deficiency anemia in a sample of northern Albanian children. A group
      of 112 children aged 6-60 months, recruited during the routine vaccinations, was
      enrolled in a cross-sectional health examination survey that included venou blood
      measurements of iron status. The survey was conducted during 2000 in Lezha
      District. The mean age was 17.1 +/- 10 months, the majority of the children were
      living in rural areas (61%), 47.8% were female. The mean level of hemoglobin was
      lower than the reference value (10.3 +/- 1.1). Iron deficiency Anemia occurred in
      47 children (47%) and more likely during the first year of the life (51%). Fifty
      seven children were fed with whole cow's milk, among them 44 were IDA. The risk
      value to be anemic or iron deficient for infants aged 6 to 12 months that were
      fed with whole cow's milk before the fourth months of life was high (OR = 6.2
      (C.L.1.0-38)). In conclusion, the high prevalence of IDA and the relationship
      with early feeding of whole cow's milk suggest to consider iron deficiency in
      infancy and childhood in Albania as an important nutritional public health
      problem and to implement strategies for his detection, treatment and prevention.

PMID- 15869169
TI  - [Mini Nutritional Assessment (MNA) and nutritional risk in elderly. A proposal of
      nutritional surveillance system for the Department of Public Health].
AB  - Objective of the study is to present an intervention model to evaluate
      nutritional risk of institutionalised elderly, suitably with the aims and
      resources of the Hygiene of Nutrition Services, and to individuate predictive
      variables of nutritional vulnerability. 237 subjects from the residential homes
      of ASL RMB were involved in the study; to each subject was administered: a) the
      Mini Nutritional Assessment (MNA); b) a questionnaire for the analysis of the
      risk factors. Multivariate logistic regression analysis was performed to evaluate
      the influence of the risk factors on nutritional status. On the basis of BMI the
      prevalence of malnutrition is 6.5% and the prevalence of overweight and obesity
      is respectively 41.6% and 22.9%; on the basis of MNA, 5.1% of the subjects is
      malnourished and 60.3% at risk for malnutrition. The absence of chewing
      difficulties (OR 2.94; I.C. 1.46-5.91) and the habit to eat all foods served at
      meals (OR 2.83; I.C. 1.46-5.91) are associated with a good nutritional status.
      The age > or = 90 years is a risk factor for malnutrition at the limit of
      statistical significance (OR 0.44; I.C. 0.14-1.00). Carrying out the MNA resulted
      easy and quick, confirming the hypothesis for feasibility of this protocol in the
      Hygiene of Nutrition Services. The results highlight an high nutritional risk of
      the elderly nursing home residents and the importance of planning programs of
      nutritional surveillance with particular attention on masticatory function
      impairments, meal intake and on the oldest subjects among the elderly as a group
      greatly vulnerable. We believe that these areas are very important in defining
      public health intervention programs.

PMID- 15869170
TI  - Drinking habits and performance in an attention test in young people frequenting
      discotheques.
AB  - Throughout July and August 2002, at the same time as a campaign on driving
      safety, questionnaire and breath alcohol tests was submitted to young people
      outside the best-frequented discotheques of the Apulia area (Italy), to describe
      the role of alcohol intake in the evening-time amusement and assess its influence
      on their attention level. 217 young people, aged between 18-30 years, accepted to
      fill in a questionnaire, and undergo a 'breathalizer' test and attention test,
      before and after having spent time in the discotheque. The score difference
      between entry and exit on the attention test was -1.48 points and alcohol blood
      level increase up to 0.14 g/l. Established the lower reference limit for the
      attention test to be 21 points, it was found that 9.7% had an attention score
      lower than the reference limit, and 61.9% of this group had a blood alcohol level
      higher than 0.5 g/l. A linear regression model between the difference of blood
      alcohol level before and after the time spent in the discotheque and attention
      score on exiting from it, turned out to be statistically significant. It's
      necessary to go on with continuous police checks and informative awareness
      campaigns regarding alcohol use, driving and night amusement.

PMID- 15869171
TI  - [Association between drug, alcohol and tobacco use in adolescents and socio
      familiar factors].
AB  - Substance abuse is the result of interaction between constitutional,
      environmental and socio-demographic factors. Several studies have been
      demonstrated that the adolescent substance abuse is a serious and growing
      problem. The aim of our study is to investigate the association between
      substance, alcohol and tobacco abuse and socio-familiar factors, to evaluate a
      substance abuse prevention program which decreases substance use in adolescents.
      A cross-sectional survey was developed and carried out by involving a group of
      adolescents, randomly selected from the secondary school of Teramo province. Data
      were collected by a self-administered questionnaire. The associations between
      substance use and the determinants taken into account was evaluated by the chi
      square test of Fisher exact test or trend test when appropriated. Our data show
      that the alcohol abuse is more frequent in males (41.1%, p = 0.000), while the
      nicotine abuse is more frequent in females (46.1%, p = 0.005). However, our
      results show that the abuse of alcohol, nicotine, heroine, cocaine and ecstasy is
      associated to lack of stability in the family, respectively: 61.5% (p = 0.001);
      61.5% (p = 0.022); 7.7% (p = 0.018); 7.7% (p = 0.010): 7.7% (p = 0.004). The
      nicotine abuse is higher in adolescents living with a smoker: 50.3% (p = 0.000).
      Finally, the substance abuse is higher in adolescents having friends that are
      drug-addicts, in particular: alcohol 49.6% (p = 0.000), nicotine 43.0% (p =
      0.000), cannabis 27.9% (p = 0.000). This survey suggests that the knowledge of
      factors influencing the initiation, combination and cessation of the use of
      substance is crucial for the prevention of drug use among adolescents.

PMID- 15869172
TI  - [Retrospective survey on epidemiologic monitoring of accidents due to
      professional exposure to biological agents in A.O.U. "G. Martino" of Messina,
      Italy)].
AB  - The management of healthcare professionals exposed to biological material which
      may potentially be contaminated with HIV HBVand HCV viruses, is of vital
      importance in acquiring precise epidemiological data regarding the type and means
      of exposure, and the efficacy or failure to apply recommended preventive
      measures. This will make it possible to assess over time which measures need to
      be implemented or improved. For these reasons we decided to analyze cases of
      occupational exposure to biological risk occurring in the University Hospital in
      Messina between 1998 and 2002. Our study highlighted in particular that the most
      frequently affected category was that of professional nurses (46.74%) and that
      only 31.72% of the healthcare workers who tested negative for HBsAb were
      administered vaccine prophylaxis also after the accident. Moreover, it emerged
      that there is the need to increase the amount and quality of information made
      available, by changing report forms, with the aim of identifying problems and
      risky behavior and procedures, and thus make ways to ensure the continued
      improvement of the accident prevention and management programmes. In fact, in the
      accident reporting procedure used, it was not possible to specify the precise way
      in which the accidents happened.

PMID- 15869173
TI  - [Evaluation of dairy production in the alpine regions of Valcamonica and Sondrio,
      and the adherence to hygienic practice guidelines].
AB  - The Regional Veterinary Service of Lombardy (northern Italian region) developed
      guideline on good hygienic practices to improve the safety of milk production and
      transformation in the mountain pastures and to grant the European acknowledgment
      (EU seal). Therefore we carried out 26 inspections in Valcamonica (Province of
      Brescia) and 30 in the Sondrio's province (26% and 16% respectively) in mountain
      pastures that had required the acknowledgment. The data analysis has shown that
      in Valcamonica 26.9% of the mountains pastures was conform to the regulations, in
      Sondrio's province instead 6.6% was conform; the frequency of acceptable
      conformity level increases respectively to 46% and to 33%, if we also consider
      the mountains pastures in restructuring phase and with very low level of non
      conformity. Our study emphasizes the need of structural adjustments of these
      traditional setting and of education of workers in order to improve the food
      safety and operator's life quality, and also to promote the maintenance of
      mountain pastures in the Alpine region.

PMID- 15869174
TI  - Seasonal evaluation and spatial variability of suspended particulate matter in
      the vicinity of a large coal-fired power station in India--a case study.
AB  - Coal combustion in the power sector gives rise to the emission of primary and
      secondary particulate pollutants. Since the emission of pollutants depends on
      coal quality and combustion technology, and given that transport, transformation
      and deposition of contaminants depend on regional climatic conditions, specific
      studies for the power stations is needed to evaluate their environmental impacts.
      Monitoring of ambient respirable suspended particulate matter (RSPM) and
      suspended particulate matter (SPM) levels around a large coal-fired power station
      in India was carried out. The specific objectives were the determination of
      spatial and seasonal variability in RSPM and SPM levels, and their relationship
      with meteorological parameters such as wind velocity and relative humidity. The
      results have shown a marked seasonal trend and spatial variability in RSPM and
      SPM levels in the study area. Higher concentrations of ambient RSPM and SPM were
      found in downwind monitoring stations compared to upwind direction. Ratios of
      RSPM to SPM and correlation coefficient values between RSPM and SPM along with
      meteorological parameters were also worked out. Relative humidity and wind
      velocity have shown an inverse relation with particulate deposition pattern.

PMID- 15869175
TI  - Assessment of elemental contaminants in water and fish samples from Aba river.
AB  - The elemental contaminants in water and fish samples from Aba river were studied.
      The elements studied were Zn, Ni, As, Hg, Co and Mn. Three water samples and
      three samples of different fish species were collected from different locations
      in the river. The water and fish samples were analysed for elemental contaminants
      using Atomic Absorption Spectrophotometer (AAS). The elemental toxicants Zn and
      Mn were identified in appreciable amounts in fresh fish species namely, Lates
      niloticus and Oriochronis niloticus, of mean values 8.012 ppm and 0.861 ppm,
      respectively. The analysis also shows arsenic concentration of mean value 0.01
      ppm in Lates niloticus. The analysis of frozen fish samples purchased from the
      Waterside market located near the river shows Ni and Hg levels of mean values
      0.83 ppm and 0.02 ppm, respectively. The levels of elemental contaminants As, Zn,
      Hg and Mn from the water samples have mean values 0.082 ppm, 11.284 ppm, 0.201
      ppm and 1.024 ppm, respectively. There are five industries that discharge waste
      products into Aba river. In view of this, there is a need to determine the level
      of pollution of the river, since the inhabitants depend on the river for their
      drinking water, fishing and other domestic uses. This study is aimed at
      determining the level of heavy metal toxicants in fish and water samples from the
      river. The effect of these elemental contaminants and the associated health
      hazards were examined.

PMID- 15869176
TI  - Three-year monitoring results of nitrate and ammonium wet deposition in Thailand.
AB  - Wet deposition is one of the important sources of nitrogen input into the
      ecosystem. It also contributes to rain acidity in some environments. In this
      study we reported the annual as well as seasonal trends of nitrogen wet
      deposition at three locations in Thailand: Bangkok, Chiang Mai and Nan.
      Comparison of nitrogen wet deposition between in rural and in the urban areas was
      also made. Daily rainfall was measured and monthly rainwater was collected for
      nitrogen analysis during 1999-2002. The average NO3- concentration in rainwater
      collected from the rural sites (60 km from urban area) was around 0.2-0.3 mg L(
      1), while that from the urban areas of Chiang Mai and Nan cities it was 0.4-0.5
      mg L(-1). NH4+ concentration in rainwater showed the similar ranges to that of
      NO3-, except at Nan where concentration was not significantly different between
      the urban and rural sites. On the other hand, the average concentrations of NO3-
      were higher at Bangkok site than other sites, while concentration of NH4+ was
      almost the same between Chiang Mai and Bangkok. Wet deposition of NO3- at the
      rural sites of Chiang Mai and Nan ranged from 2.1 to 3.2 kg N ha(-1) yr(-1),
      while at the urban sites this ranged from about 6 kg N ha(-1) yr(-1) in Chiang
      Mai and Nan Cities to 8.6 kg N ha(-1) yr(-1) in Bangkok. Wet deposition of NH4+
      at the rural sites of Chiang Mai and Nan was about 2.4 to 3.6 kg N ha(-1) yr(-1)
      and at the urban sites of Chiang Mai, Nan and Bangkok this was 7.7, 4.9 and 8.1
      kg N ha(-1) yr(-1), respectively. Thus, it was concluded that wet deposition of
      both nitrogen species was significantly higher at the urban sites than at the
      rural sites.

PMID- 15869177
TI  - Environmentally stratified sampling design for the development of Great Lakes
      environmental indicators.
AB  - Understanding the relationship between human disturbance and ecological response
      is essential to the process of indicator development. For large-scale
      observational studies, sites should be selected across gradients of anthropogenic
      stress, but such gradients are often unknown for apopulation of sites prior to
      site selection. Stress data available from public sources can be used in a
      geographic information system (GIS) to partially characterize environmental
      conditions for large geographic areas without visiting the sites. We divided the
      U.S. Great Lakes coastal region into 762 units consisting of a shoreline reach
      and drainage-shed and then summarized over 200 environmental variables in seven
      categories for the units using a GIS. Redundancy within the categories of
      environmental variables was reduced using principal components analysis.
      Environmental strata were generated from cluster analysis using principal
      component scores as input. To protect against site selection bias, sites were
      selected in random order from clusters. The site selection process allowed us to
      exclude sites that were inaccessible and was shown to successfully distribute
      sites across the range of environmental variation in our GIS data. This design
      has broad applicability when the goal is to develop ecological indicators using
      observational data from large-scale surveys.

PMID- 15869178
TI  - Heavy metals in ryegrass species versus metal concentrations in atmospheric
      particulate measured in an industrial area of Southern Italy.
AB  - The aim of this paper is to evaluate the reliability of ryegrass species as
      active biomonitors by assessing atmospheric metal concentrations. We show a
      procedure for measuring atmospheric concentrations of heavy metals by means of
      biomonitors and present the data collected between July 1997 and October 2000 in
      the industrial area of Tito Scalo (Basilicata region, Southern Italy). In
      particular, we discuss the reproducibility of the biomonitoring measures, the
      influence of plant age and the correlation between metal concentrations in plants
      and in atmospheric particulate. Statistical analysis of measured data suggests us
      that in the investigated site, Cd, Cr and Ni are suitable to be monitored by
      means of ryegrass species. For the other metals, their emission patterns in
      atmosphere make it difficult to identify the correlation structure between plants
      and particulate, and as a result the interpretation of the biomonitoring data is
      complex. On the basis of the results, we believe that for correct application of
      active biomonitoring procedure, a careful preliminary analysis of the monitoring
      site and integration of the biomonitoring and chemical-physical observation is
      necessary.

PMID- 15869179
TI  - Size distribution in ultraphytoplankton: a comparative analysis of counting
      methods.
AB  - Water samples taken at three depth layers from the offshore oligotrophic Cretan
      Sea were analyzed for ultraphytoplankton size fractionation using different
      methods: (a) sequential filtration on filters of pore size 5, 1 and 0.2 microm,
      (b) separate filtration using filters 5 and 0.2 microm as well as 1 and 0.2
      microm and (c) direct filtration on 0.2 microm filters after staining of the
      samples with DAPI. Total abundance of photosynthetic organisms as well as the
      abundance of different groups such as flagellates and cyanobacteria measured by
      means of sizing after DAPI staining were significantly higher than those obtained
      by the other methods. This indicates that although there were no significant
      differences between the estimates provided by the separate and sequential
      filtration, both these methods underestimated total abundance by at least 25-50%.
      The estimates for the size fractions were also found to range from relatively
      imprecise to completely unreliable depending on the group and the size range.
      Although size fractionation through direct observation after staining largely
      depends on the expertise of the observer, this study suggests that it may provide
      more informative estimates than the other two methods. Although it is difficult
      to generalize the results of this study in a global context, the paper provides
      strong indications on the limitations of the sequential and separate methods for
      size fractionation of photosynthetic organisms and implies that their results are
      likely to be less accurate than is presently believed.

PMID- 15869180
TI  - Phosphorus losses from arable fields in Sweden--effects of field-specific factors
      and long-term trends.
AB  - Accelerated eutrophication of surface water is often caused by high phosphorus
      (P) losses from agricultural fields. Long-term measurements of P concentrations
      from arable fields are therefore important for understanding of processes and key
      factors behind losses. Unfortunately, long-time series are difficult to compare
      due to high variablity, non-normal distribution, precipitation variability and
      flow relatedness. The objective was to use locally weighted scatterplot smoothing
      (LOWESS) and Seasonal Kendall Test to account for discharge effects on
      concentrations of P forms and suspended soil material, and to identify trends for
      seven agricultural fields included in a Swedish water quality monitoring program.
      Soil P content and sorption capacity governed concentrations and losses of
      dissolved reactive phosphorus (DRP). Other factors, such as preferential flow may
      influence the importance of these factors. Suspended soil material and unreactive
      phosphorus (UP) concentrations in water discharge depended on soil texture, slope
      of the field and total soil P content. Statistically significant trends in
      concentrations of different P forms were found for two fields. These trends are
      probably a consequence of changes in P additions and soils P saturation levels.

PMID- 15869181
TI  - Characterisation of particulate matter for toxic metals in ambient air of Kochi
      city, India.
AB  - Measurement of respirable suspended particulate matter (RSPM) and analysis of
      toxic metals in air of Kochi city was carried out for a period of one year, 1997.
      Seasonal variations of RSPM and toxic metals are analysed to identify the
      influence of meteorological parameters. The air pollution problem with respect to
      RSPM and lead is moderately significant especially in winter season. The profile
      of other toxic metals in RSPM is not much significant. Domestic fuel used mainly
      coal/wood and petrol/diesel fueled motor vehicles are the major contributors to
      the RSPM and toxic metals. Various control strategies are delineated for
      reduction of ambient RSPM and toxic metals in air of Kochi city.

PMID- 15869182
TI  - Monitoring E. coli and total coliforms in natural spring water as related to
      recreational mountain areas.
AB  - Natural spring water has unique properties, as it is rich in minerals that are
      considered to be beneficial to human health. A survey of the microbiological
      quality of natural spring water was conducted to assess possible risks from the
      consumption of the water by visitors in recreational mountain areas located in
      Seoul, South Korea. The densities of total coliforms and Escherichia coli were
      measured during the spring and the summer of 2002 to investigate the presence of
      coliform bacteria in the drinking spring waters. Total coliforms were detected in
      all samples and the mean density of total coliforms was up to a maximum of 228
      CFU/mL. Detectable E. coli was found in 78% of all samples and the mean densities
      of E. coli varied from a minimum of 0 CFU/mL to a maximum of 15 CFU/mL in all
      samples. Malfunctioning septic systems and wildlife population appear to be the
      main source of E. coli contamination. Presence of E. coli in natural spring water
      indicates potential adverse health effects for individuals or populations exposed
      to this water. The fecal contaminated spring water may present an unacceptable
      risk to humans if it is used as raw drinking water.

PMID- 15869183
TI  - Phase I of the Kissimmee River restoration project, Florida, USA: impacts of
      construction on water quality.
AB  - Phase I of the Kissimmee River restoration project included backfilling of 12 km
      of canal and restoring flow through 24 km of continuous river channel. We
      quantified the effects of construction activities on four water quality
      parameters (turbidity, total phosphorus flow-weighted concentration, total
      phosphorus load and dissolved oxygen concentration). Data were collected at
      stations upstream and downstream of the construction and at four stations within
      the construction zone to determine if canal backfilling and construction of 2.4
      km of new river channel would negatively impact local and downstream water
      quality. Turbidity levels at the downstream station were elevated for
      approximately 2 weeks during the one and a half year construction period, but
      never exceeded the Florida Department of Environmental Protection construction
      permit criteria. Turbidity levels at stations within the construction zone were
      high at certain times. Flow-weighted concentration of total phosphorus at the
      downstream station was slightly higher than the upstream station during
      construction, but low discharge limited downstream transport of phosphorus. Total
      phosphorus loads at the upstream and downstream stations were similar and loading
      to Lake Okeechobee was not significantly affected by construction. Mean water
      column dissolved oxygen concentrations at all sampling stations were similar
      during construction.

PMID- 15869184
TI  - Bioindicator organisms: heavy metal pollution evaluation in the Ionian Sea
      (Mediterranean Sea--Italy).
AB  - Trace metal concentrations of mercury, cadmium, lead and chromium in Patella
      caerulea, and Mullus barbatus were investigated to provide information on
      pollution of Ionian Sea, since these metals have the highest toxic potential.
      High chromium levels (0.47-0.97 microg g(-1) ww) were registered in limpet
      samples collected from two station near the Gulf of Taranto, while elevated
      concentration of mercury (0.31-1.50 microg g(-1) ww) were found in mullet
      specimens from Sicily. The metal concentrations recorded at the clean stations
      may be considered as useful background levels to which to refer for comparison
      within the Mediterranean area. On the contrary, the high levels of chromium and
      mercury found respectively in the areas near the Gulf of Taranto and at Capo
      Passero being of concern in terms of environmental health need frequent
      monitoring.

PMID- 15869185
TI  - Using slides to test for changes in crown defoliation assessment methods Part II:
      Application of the image analysis system CROCO.
AB  - We tested whether the semi-automatic program CROCO can replace visual assessments
      of slides to detect changes in defoliation assessment methods. We randomly
      selected a series of slides of 24 Norway spruce trees with 220 field assessments
      made between 1986 and 1995. The slides had been randomly arranged and assessed by
      three experts without knowledge of the tree number or the year when the slide was
      taken. Defoliation scores were computed with CROCO. Each tree had thus three
      different defoliation scores, field assessments, photo assessments and CROCO
      scores. CROCO scores were less correlated with the field assessments (Spearman's
      rank correlation: 0.67) than were the slide assessments with the field
      assessments (0.79-0.83). However, CROCO was not biased against the field scores,
      while slide assessments systematically underestimated defoliation. In a multi
      variate mixed effect model none of the variables tree overlap, tree visibility
      and light conditions was significant in explaining differences between slide
      assessors and CROCO scores. The same model applied for the differences from the
      field scores yielded significant effects for poor light conditions (CROCO and all
      assessors), for crown overlap (CROCO and one assessor) and for visibility (one
      assessor). We conclude, therefore, that CROCO can be used to detect past and
      future changes in assessment methods without bias if poor quality photographs are
      avoided.

PMID- 15869186
TI  - Statistical analyses of coastal water quality for a port and harbour region in
      India.
AB  - A long-term study of temperature, pH, turbidity, suspended solid, salinity,
      dissolved oxygen, biochemical oxygen demand and ammonia nitrogen has been
      performed in a port and harbour region in India for four years from December 1996
      to November 2000. Marine water quality results showed no regular trend. The mean
      monthly values of temperature, pH, turbidity, suspended solid, salinity,
      dissolved oxygen, biochemical oxygen demand and ammonia nitrogen were in the
      range of 22.64 +/- 0.4 to 29.05 +/- 1.37 degrees C; 7.65 +/- 0.04 to 7.81 +/-
      0.13; 28.8 +/- 14.7 to 64.2 +/- 32.0 NTU; 283.5 +/- 81.8 to 356.0 +/- 159.7 mg/L;
      29.78 +/- 7.18 to 29.78 +/- 1.04 ppt; 4.67 +/- 0.50 to 6.01 +/- 1.02 mg/L; 5.41
      +/- 1.92 to 7.56 +/- 2.1 mg/L; and 0.25 +/- 0.07 to 0.63 +/- 0.49 mg/L,
      respectively. The results of correlation analysis showed that biochemical oxygen
      demand (BOD) was inversely correlated dissolved oxygen (DO) and poorly correlated
      with all other parameters. Turbidity and suspended solid were moderately
      correlated with each other while salinity was moderately correlated with other
      water quality parameters. In factor analysis, four factors were drawn out of the
      eight variables, which represented 74% of the variance of the original data.
      Factor I was related to suspended solid and turbidity. Factor II represented
      mainly temperature and DO showing inverse relation between these two. Factor III
      implied the degree of pollution at any monitoring station. Factor IV included pH
      and salinity. It could be concluded that the factor model represented almost all
      the variables.

PMID- 15869187
TI  - Effects of meteorological conditions on PM10 concentrations--a study in Macau.
AB  - Review on the annual PM10 concentrations over a 10-year period shows that Macau
      is subjected to severe fine particulate pollution. Investigations of its
      variation in monthly and daily time scales with the local meteorological records
      reveal further details. It is found that a distinct feature of the Asian monsoon
      climates, the changes of wind direction, mainly controls the general trend of
      PM10 concentration in a year. The monsoon driven winter north-easterly winds
      bring upon Macau dry and particle enriched air masses leading to a higher
      concentration in that period while the summer south-westerly winds transport
      humid and cleaner air to the region leading to a lower PM10 value. This distinct
      seasonal feature is further enhanced by the lower rainfall volume and frequency
      as well as mixing height in winter and their higher counterparts in summer. It is
      also found that the development of tropical cyclones near Macau could also impose
      episode like PM10 concentration spikes due to the pre-typhoon induced stagnant
      air motion followed by the swing of wind direction to the northerly.

PMID- 15869188
TI  - Nitrate leaching in agriculture to upper groundwater in the sandy regions of the
      Netherlands during the 1992-1995 period.
AB  - The Dutch National Monitoring Programme for Effectiveness of the Minerals Policy
      (LMM) was initiated to allow detection of a statutory reduction in nitrate
      leaching caused by a decreasing N load. The starting point, or baseline, was
      taken as the nitrate concentration of the upper metre of groundwater sampled on
      99 farms in the 1992-1995 period in the sandy areas of the Netherlands, where
      predominantly grass and maize grow. We found here that a reduction in nitrate
      leaching of more than 20% in future would almost certainly be detected with the
      LMM. Detecting downward trends due to decreasing N load will require nitrate
      concentrations to also be related to soil drainage, precipitation excess leading
      to groundwater recharge and to location. Furthermore, we found that about 16% of
      the N load in the Dutch sandy regions was being leached to the upper metre of
      groundwater in the 1992-1995 period. The critical N load in approximately 1990
      for exceeding the EC limit value for nitrate, NO3, (50 mg L(-1)) in the upper
      metre of groundwater for the mean situation for grassland, maize and arable land
      in the sandy area was found to be 210 kg ha(-1) a(-1). Because manure management
      has been altered, the critical load found will be lower than the current critical
      load.

PMID- 15869189
TI  - Comparison of macroinvertebrate sampling methods for nonwadeable streams.
AB  - Bioassessment of nonwadeable streams in the United States is increasing, but
      methods for these systems are not as well-developed as for wadeable streams. In
      this study, we compared six macroinvertebrate field sampling methods for
      nonwadeable streams adapted from those used by three major programs: the U.S.
      Environmental Protection Agency's Environmental Monitoring and Assessment Program
      Surface Waters, the U.S. Geological Survey's National Water Quality Assessment
      Program, and the Ohio Environmental Protection Agency, Division of Surface Water
      Biocriteria Program. We performed all six methods at 60 sites across four rivers
      and measured water chemistry and physical habitat at each site to assess abiotic
      conditon. Sites were divided into two groups: those influenced by navigational
      lock and dam structures (restricted flow, or RF) and those free-flowing or with
      lowhead dams (run-of-the-river, or ROR). Metrics based on passive Hester-Dendy
      artificial substrate samplers differed greatly from active sampling methods
      (i.e., using nets) but represented abiotic conditions well in both ROR and RF
      sites. Although metric values were similar across certain sampling methods, the
      metrics significantly correlated with abiotic variables varied among methods and
      between ROR and RF sites. These results emphasize that methods are not
      interchangeable, and the ability to detect certain stressors depends on sampling
      method.

PMID- 15869190
TI  - Electrofishing in boatable rivers: does sampling design affect bioassessment
      metrics?
AB  - Data were collected from 60 boatable sites using an electrofishing design that
      permitted comparisons of the effects of designs and distances on fish assemblage
      metrics. Sites were classified a priori as Run-of-the-River (ROR) or Restricted
      Flow (RF). Data representing four different design options (i.e., 1000 and 2000 m
      for both single and paired banks) were extracted from the dataset and analyzed.
      Friedman tests comparing metric values among the designs detected significant
      differences for all richness metrics at both types of sites and for catch per
      unit effort and percent tolerant species at ROR sites. Richness metrics were
      generally higher for the two 2000-m designs than for the two 1000-m designs. When
      plotted against cumulative electrofishing distance, the percent change in metrics
      declined sharply within approximately 1000 m, after which metrics usually varied
      by less than 10%. These data demonstrate that designs electrofishing 1000 m of
      shoreline are sufficient for bioassessments on boatable rivers similar to those
      in this study, regardless of whether the shoreline is along a single bank or
      distributed equally among paired banks. However, at sites with depths greater
      than 4 m, it may be advisable to employ nighttime electrofishing or increase day
      electrofishing designs to 2000 m.

PMID- 15869191
TI  - Floristics, performance and prognosis of historical trees in the urban forest of
      Guangzhou city (China).
AB  - Outstanding historical trees embedded in cities constitute pertinent
      environmental assets, yet they are widely threatened in third-world cities.
      Inadequate understanding of this valuable natural-cum-cultural heritage hinders
      proper conservation. A case study of Guangzhou in south China evaluated floristic
      composition, age profile and biomass structure of historical trees, assessed
      their performance in major habitats (institutional, park and roadside), and
      established a prognosis for future growth and management. The 348 historical
      trees examined belonged to only 25 species, vis-a-vis 254 trees in the entire
      urban forest, dominated by five species and native members. Roadside had more
      trees, followed by institutional and park, with merely the most common four
      species shared by all habitats. The limited commonality reflected tree
      performance differentiation by habitats exerting selection pressure on species.
      The institutional growth-regime was more conducive to nurturing high-caliber
      specimens, whereas park is less capable. Individual species achievement by
      habitats, derived from tree-count ranking and relative-abundance indices, could
      inform species choice and tree conservation. Few trees exceeded 300 years of age
      in the millennium-old city, echoing a history of intense tree-city conflicts.
      Potential life-span, trunk and crown diameters indicated ample opportunities for
      further expansion of biomass and landscape impacts, which would be straitjacketed
      by the tightening urban fabric.

PMID- 15869192
TI  - Artemia salina as test organism for assessment of acute toxicity of leachate
      water from landfills.
AB  - Artemia salina has, for the first time, been used as test organism for acute
      toxicity of leachate water from three landfills (the municipal landfills at
      Kristianstad, Sweden and Siauliai, Lithuania, and an industrial landfill at Stena
      fragmenting AB, Halmstad, as well as for leachate from Kristianstad treated in
      different ways in a pilot plan). Artemia can tolerate the high concentrations of
      chloride ions found in such waters. Large differences in toxicities were found,
      the leachate from Siauliai being the most toxic one. To increase the selectivity
      in the measurements, a fractionation was done by using ion exchange to separate
      ammonium/ammonia and metal ions from the leachate, and activated carbon
      adsorbents for organic pollutants. The influence of some metals and phenol
      compounds on the toxicity was investigated separately. It was found that most of
      the toxicity emanated from the ammonium/ammonia components in the leachate.
      However, there was also a significant contribution n from organic pollutants,
      other than phenol compounds, since separate experiments had in this latter case
      indicated negligible impact. The concentrations of metals were at a level, shown
      by separate experiments, where only small contribution to the toxicity could be
      expected.

PMID- 15869193
TI  - Developing a suitability index for land uses and agricultural land covers: a case
      study in Turkey.
AB  - This study was aimed at determining the land-use and land-cover (LULC) potentials
      of a southeastern Mediterranean area (Antakya, Turkey) of 36 816 ha for a total
      of 23 different LULC types: nine horticultural crops, nine field crops and five
      non-agricultural lands. Land evaluation was carried out by using a combination of
      SENOL Land Evaluation System and ILSEN computer program adapted to Turkey from
      FAO land evaluation principles. Our assessment resulted in the identification of
      nine physiographical units, 27 different soil series, and 110 land mapping units.
      Nearly 49% of the study area was determined as suitable for agricultural land
      cover types, and 35% for non-agricultural land use types. A map showing potential
      suitability of LULC was derived for the study area. The quantification of LULC
      suitability assists decision makers in ensuring that lands are used according to
      their capacities to satisfy human needs for present and future generations, thus
      sustaining ecological and economic productivity of natural resources.

PMID- 15869194
TI  - Monitoring perchlorate exposure and thyroid hormone status among raccoons
      inhabiting a perchlorate-contaminated site.
AB  - Perchlorate is a water soluble anion that is readily accumulated in vegetation.
      It inhibits uptake of iodide into thyroid gland tissue, thereby reducing
      production of thyroid hormones. Potential raccoon food items including berries,
      fish, and vegetation collected at a contaminated site contained quantifiable
      concentrations of perchlorate as determined by ion chromatography. Therefore, we
      monitored resident raccoons for exposure to perchlorate by examining plasma
      perchlorate and thyroid hormone concentrations. Resulting analytical data failed
      to demonstrate perchlorate exposure among raccoons that likely consumed food
      items collected along perchlorate-contaminated water bodies. There were no
      correlations between triiodothyronine or thyroxine and thyroid stimulating
      hormone concentrations, but triiodothyronine concentrations in raccoon plasma
      were significantly higher in 2000 than in 2001 (p = 0.0081). These data suggest
      that natural attenuation and remedial efforts initiated in January of 2001 may
      have reduced perchlorate exposure among raccoons inhabiting this site from 2000
      to 2001. Temporal, spatial, and analytical factors limited our ability to
      quantify exposure among raccoons, however, our data do not indicate that raccoons
      currently inhabiting this site are at risk for significant exposure to
      perchlorate and subsequent effects.

PMID- 15869195
TI  - Inorganic chemical composition of native trees of the Atlantic Forest.
AB  - The Atlantic Forest with its exuberant vegetation of high level of biodiversity
      is classified as one hotspot of the world. Chemical composition of leaves from
      native trees and underlying soils was evaluated by INAA. The predominant species
      Euterpe edulis, Bathysa meridionalis, Hyeronima alchorneoides, Marlierea
      tomentosa, Gomidesia flagellaris, and Gomidesia spectabilis belonging to the
      diverse plant families were studied. Euterpe edulis, the most abundant understory
      specie, presented the lowest element concentrations except for Zn. Some variation
      in chemical composition was noted, however, the chemical specificity of tree
      species can be more predominant than the soil variability for the obtained leaf
      concentrations. Factor values obtained through the Monte-Carlo assisted factor
      analysis were used for species discrimination, The results indicate that chemical
      investigation of native trees is a quite promising tool for biodiversity studies
      in the Atlantic Forest.

PMID- 15869196
TI  - Factors affecting N and P losses from small catchments (Lithuania).
AB  - Most of the important factors causing differences in nutrient losses and their
      interaction were analysed in three small catchments that are located in partially
      different geographic and climatic conditions in Lithuania. The investigation
      revealed that climatic factors change the amount and pattern of water discharge
      over year (larger water discharge during winter in the catchment located closer
      to the sea), but nutrient leaching is more dependent on land use. Agricultural
      factors, such as larger cultivated area and excessive fertilisation in one
      catchment cause larger nitrogen losses (15 kg N ha(-1) year(-1)). Large area of
      non-intensively used grassland leads to very small nitrogen losses (5.7 kg N ha(
      1) year(-1)) in another catchment. However, larger water discharge combined with
      loamy sandy soils leads to comparatively high nitrogen losses (12 kg N ha(-1)
      year(-1)). The highest P losses (0.318 kg P ha(-1) year(-1)) occurred in the
      catchment with hilly relief and clay soil texture. In summary, extensive
      agriculture in the post-Soviet countries has reduced the importance of
      agricultural activity for the extent of nutrient losses and agricultural factors
      (cultivation, fertilisation and livestock density) are 'responsible' for the
      losses only in the region of sufficient agricultural activity (N input--71.5 kg N
      ha(-1), livestock density--0.87 LU ha(-1)).

PMID- 15869197
TI  - How many samples are required? Evaluating a model for verification of carbon
      sequestration in a hybrid poplar buffer strip.
AB  - A model is developed to predict annual and total above-ground carbon storage
      within a hybrid poplar stream buffer. The regression model predicts tree wet
      weight based upon circumference at breast-height (137 cm) with an r-square value
      of 0.9922. Carbon storage in above-ground biomass is estimated to be 3.57 to 3.71
      metric tons per hectare, with a measured annual increment of 0.92 to 1.37 metric
      ton per hectare per year. The variability of carbon storage within this
      biological system, including soil organic matter, is explored, and the number of
      samples required to achieve a desired level of statistical certainty are
      predicted. As has been investigated previously for other biological systems
      (Garten and Wullschleger, 1999), the study shows that a prohibitively large
      number of samples must be taken in order to achieve high degrees of certainty
      about mean carbon storage values. The study also shows, however, that mean values
      with somewhat greater uncertainties can easily be achieved with much smaller
      sample sizes. Thus carbon sequestration verification might be accomplished cost
      effectively if the degree of certainty required is not unrealistically high for
      highly variable natural systems.

PMID- 15869198
TI  - Synchronous variation in water chemistry for 80 lakes in southern Sweden.
AB  - Variation in water chemistry was studied in 80 lakes in southern Sweden. The
      lakes had forest dominated catchments. The length of the time series was 14
      years. Synchrony was calculated as Pearson's product moment correlation
      coefficients for all combinations of lakes, i.e. 3160 lake-pairs. The chemical
      variables studied were non-marine sulphate (SO4*), non-marine calcium (Ca*),
      absorbance and acid neutralising capacity (ANC). Statistically significant
      synchrony occurred in 93% of all lake-pairs for SO4*, and between 58 and 67% for
      absorbance, Ca* and ANC. In 70% of all lake-pairs, the synchrony was >0.71 for
      SO4*, which means that more than half of the variation in one lake could be
      explained by the variation in the other lake. For absorbance, Ca* and ANC, about
      25% of the lake-pairs had a synchrony >0.71. The relatively high synchrony for
      SO4* occurred during an overall downward trend in SO4* concentration. The degree
      of synchrony in our study was at a level comparable to other studies in northern
      America and England. However, our study included lakes in a much larger area,
      with distances of up to 500 km between the lakes, while earlier studies were made
      on small lake districts with lakes located within approximately 50 km. In
      contrast to these earlier studies, there was no correlation between synchrony and
      distance, lake characteristics or catchment characteristics. However, when a
      small subset of 15 lakes in the southeast of Sweden was selected, such relations
      were found.

PMID- 15869199
TI  - Multivariate analysis of heavy metal contents in soils, sediments and water in
      the region of Meknes (central Morocco).
AB  - Concentrations of Al, Fe, Cr, Cu, Ni, Pb and Zn in soils, sediments and water
      samples collected along the Oued Boufekrane river (Meknes, central Morocco) were
      determined. In soils, a homogeneous distribution of metal concentrations was
      observed throughout the study area except for Pb, which presents high enrichment
      at sites located at the vicinity of a main highway. In sediments, high
      enrichment, with respect to upstream sites, were observed downstream of the city
      of Meknes for Al, Cr, Fe and Ni and inside the city for Cu, Zn and Pb. In water
      samples, the metal contents showed to correlate with their homologues in
      sediments suggesting that the metal contents in water and sediments have
      identical origins. Descriptive statistics and multivariate analysis (principal
      factor method, PFM) were used to assist the interpretation of elemental data.
      This allowed the determination of the correlations between the metals and the
      identification of three main factor loadings controlling the metal variability in
      soils and sediments.

PMID- 15869200
TI  - Distribution of heavy metals in sediment and water of river Gomti.
AB  - Gomti river receives industrial as well as domestic wastes from various drains of
      Lucknow city. In the process the water and sediment of the river Gomti get
      contaminated with heavy metals and other pollutants. In the present study,
      impacts of domestic/industrial wastes on the water and sediment chemistry of
      river Gomti with special reference to heavy metals have been investigated in
      different seasons (summer, winter and rainy). For this, seven sampling sites:
      Gaughat, Mohan Meakin, Martyr's Memorial, Hanuman Setu, Nishatganj bridge,
      Pipraghat and Malhaur, in the river Gomti in Lucknow region were identified and
      samples of water and sediments were collected in all the three seasons. In the
      collected water and sediment samples, six metals (Cd, Cr, Cu, Ni, Pb, and Zn)
      were analyzed on ICP-AES (Inductively coupled plasma emission spectroscopy)
      Labtam Plasmalab 8440. High concentrations of all the metals were noticed in
      water and sediment in rainy season compared to summer and winter. Because in
      rainy season runoff from open contaminated sites, agricultural field and
      industries, directly comes into the river without any treatment. In both the
      cases, the concentration of zinc was maximum (0.091 microg/ml in water and 182.13
      microg/g in sediment) and the concentration of cadmium (0.001 microg/ml in water
      and 17.26 microg/g in sediment) was minimum. Higher concentration of metal in
      water and sediment during rainy season could be due to the
      industrial/agricultural/domestic runoff coming into the river.

PMID- 15869201
TI  - Application of a systemic approach to the study of pollution of the Tinto and
      Odiel rivers (Spain).
AB  - The province of Huelva in the SW of Spain presents high environmental contrasts:
      together with the great abundance of natural spaces, it shows the impacts of
      historical natural resources exploitation processes. In the Ria of Huelva, the
      effluents of the chemical industries must be added to the contaminating inputs of
      the Tinto and Odiel rivers, coming from the acid drainage of the mines located in
      the Iberian Pyrite Belt. This forced the Environmental Agency (AMA) to elaborate
      in 1987 an Effluent Remediation Plan in order to negate unacceptable
      environmental impacts. The application of a "grey box" systemic analysis to the
      AMD pollution, undergone by the Tinto and Odiel rivers has allowed to set a
      conclusive explanation of the sampling results observed for a period of 11 years,
      thus making available an overall view of the polluting process and, above all, an
      explanation of its partial aspects.

PMID- 15869203
TI  - Enterprise information systems and project organization type: a mixed-bag
      approach for success.

PMID- 15869202
TI  - Fly-ash-induced oxidative stress and tolerance in Prosopis juliflora L. grown on
      different amended substrates.
AB  - Field experiments were conducted to study the impact of metal accumulation on
      malondialdehyde (MDA), cysteine and non-protein thiol (NPSH) contents in the
      plants of Prosopis juliflora grown on the fly ash (FA) amended with soil, blue
      green algae (BGA) biofertilizer, farm yard manure, press mud and Rhizobium
      inoculation. The analysis of data revealed that the level of MDA, cysteine and
      NPSH was higher in the roots of the plant than leaves, which was found positively
      correlated with metal accumulation. An increase of 361.14, 64.25 and 305.62% in
      MDA, cysteine and NPSH contents, respectively was observed after 45 days in the
      roots of the plants grown in 100% FA as compared to 100% garden soil (GS). The
      level of MDA, cysteine and NPSH was found less in the plants grown on various
      amendments of FA showing ameliorating effect on the toxicity induced due to the
      accumulation of metals. The decrease in MDA, cysteine and NPSH contents was
      higher in Rhizobium-inoculated plants as compared to uninoculated plants grown on
      100% FA. The results showed a high tolerance potential of the plant, which is
      further increased by inoculating the plant with FA-tolerant Rhizobium showing
      feasibility of using P. julifilora in environmental monitoring of FA landfills.

PMID- 15869204
TI  - Avoiding the train wreck in healthcare: integrating information in the clinic and
      the back office.

PMID- 15869205
TI  - Clinical decision support and the parable of the stick shaker.

PMID- 15869206
TI  - Strengthening the links in the supply chain--some preventive medicine.
AB  - There are many links in the supply chain that can lead to a "break" in an
      organization's supply process. These breaks can waste professional and clinical
      time and take staff away from patient care activities. By paying attention to
      some key areas, designing efficient workflows, and monitoring supply usage, an
      organization can avoid the headaches of a supply process that doesn't optimize
      scarce labor resources. It also can lead to significant savings that go directly
      to the organization's bottom line. As with all hospital processes, some
      consistent and focused preventive medicine makes sense for its supply chain.

PMID- 15869207
TI  - EAI reaches outside the healthcare organization.

PMID- 15869208
TI  - Minimize large-scale IT project risks through effective contracting strategies.

PMID- 15869209
TI  - Commercial clinical data warehouses: from wave of the past to the state of the
      art.
AB  - This article provides an overview of clinical data warehousing and its historical
      perspective from the early 1990s to present. It uses a survey of five Houston
      area healthcare leaders to answer questions such as why commercially available
      solutions may be more suitable as their enterprise information systems vs.
      developing them in-house. Which products and vendors are servicing these
      organizations? What are these organizations looking for when making such
      strategic purchases? In general, this work is intended as a guideline for
      healthcare entities to further investigate the commercial clinical data
      warehousing market and get a feel for industry trends.

PMID- 15869210
TI  - The evolving role of supply chain management technology in healthcare.
AB  - The healthcare supply chain is a vast, disintegrated network of products and
      players, loosely held together by manual and people-intensive processes. Managing
      the flow of information, supplies, equipment, and services from manufacturers to
      distributors to providers of care is especially difficult in clinical supply
      chains, compared with more technology-intense industries like consumer goods or
      industrial manufacturing. As supplies move downstream towards hospitals and
      clinics, the quality and robustness of accompanying management and information
      systems used to manage these products deteriorates significantly. Technology that
      provides advanced planning, synchronization, and collaboration upstream at the
      large supply manufacturers and distributors rarely is used at even the world's
      larger and more sophisticated hospitals. This article outlines the current state
      of healthcare supply chain management technologies, addresses potential reasons
      for the lack of adoption of technologies and provides a roadmap for the evolution
      of technology for the future. This piece is based on both quantitative and
      qualitative research assessments of the healthcare supply chain conducted during
      the last two years.

PMID- 15869211
TI  - Rapid implementation of an electronic health record in an academic setting.
AB  - One of the sources of resistance to the implementation of electronic health
      records is that it often takes years to roll out a fully functional system. The
      George Washington University Medical Faculty Associates (MFA) has set a new
      standard for rapid EHR implementation by bringing 99 physicians and 130 residents
      and interns live in less than 30 days in a complex academic setting. MFA
      leveraged a rapid implementation process based on study of previous successful
      implementations. The rollout plan incorporated aggressive hands-on education, in
      person and virtual training modules for self-review, and a leadership triad of
      physicians, administrators, and information technology experts.

PMID- 15869212
TI  - National Provider Identifier (NPI) planning and implementation fundamentals for
      providers and payers.
AB  - Federal HIPAA legislation mandates that the National Provider Identifier (NPI) be
      fully implemented across all healthcare entities between May 2005 and May 2007,
      or 2008 for small payers. Starting May 2005, healthcare providers will be
      eligible to obtain an NPI and use these numbers to submit claims or conduct other
      transactions specified by HIPAA. By 2007, the NPI must be used in connection with
      the electronic transactions identified in HIPAA. Today, individual payers assign
      unique identification numbers to healthcare providers, and, in most cases, payers
      assign multiple identification numbers to healthcare providers and their
      "subparts." As a result, providers have multiple payer-specific identification
      numbers. The NPI is a unique, 10-digit federal healthcare provider identification
      number that will be used by all healthcare providers and payers and other
      healthcare entities involved in administrative and financial transactions
      associated with health service events and related activities. This article will
      use software and data experts' knowledge as well as the authors' NPI
      implementation readiness assessment work to review the impact to both payers and
      providers, including hospitals, clinics, and other service entities. The authors
      will suggest planning, budgeting, architecting, and data management solutions for
      payers and providers to achieve the optimal administrative simplification goals
      intended by the NPI, without compromising data integrity and interoperability
      objectives across the service spectrum of the healthcare enterprise.

PMID- 15869213
TI  - Making sausage--effective management of enterprise-wide clinical IT projects.
AB  - Unlike most other industries in which company employees are, well, company
      employees, U.S. hospitals are typically run by both employees (nurses,
      technicians, and administrative staff) and independent entrepreneurs (physicians
      and nurse practitioners). Therefore, major enterprise-wide clinical IT projects
      can never simply be implemented by mandate. Project management processes in these
      environments must rely on methods that influence adoption rather than presume
      adoption will occur. "Build it and they will come" does not work in a hospital
      setting. This paper outlines a large academic medical center's experiences in
      managing an enterprise-wide project to replace its core clinical systems
      functionality. Best practices include developing a cogent optimal future-state
      vision, communications planning and execution, vendor validation against the
      optimal future-state vision, and benefits realization assessment.

PMID- 15869214
TI  - Web-based communication to enhance outcomes: a case study in patient relations.
AB  - As the volume of available resources on the Internet continues to expand, more
      people turn to the Web first when researching healthcare topics and conditions.
      In fact, nearly three quarters--73 percent--of 12,000 Internet users in a recent
      survey conducted by Gomez Advisors Inc., a Lincoln, Mass.-based research and
      consulting company, reported that they had researched a health condition on the
      Web. Conducting research on a particular health condition on the Internet often
      yields vast amounts of information, much of it not relevant, specific, or even
      accurate. Therefore, it is important to tailor a search to elicit results that
      will be the most precise to a specific situation. Web sites that use "push
      technology," such as targeted e-mail, rather than a passive site that must be
      visited and surfed through, offer a more effective way of obtaining "just-in
      time" information. Such sites are able to reach people with pertinent information
      that will spark their interest, assist them in formulating questions when
      speaking to their physicians, and, above all, improve their own well-being. This
      article discusses a particular push technology strategy, how outcomes information
      was obtained to validate the strategy, and the results for a particular
      healthcare diagnosis.

PMID- 15869215
TI  - Data mining applications in healthcare.
AB  - Data mining has been used intensively and extensively by many organizations. In
      healthcare, data mining is becoming increasingly popular, if not increasingly
      essential. Data mining applications can greatly benefit all parties involved in
      the healthcare industry. For example, data mining can help healthcare insurers
      detect fraud and abuse, healthcare organizations make customer relationship
      management decisions, physicians identify effective treatments and best
      practices, and patients receive better and more affordable healthcare services.
      The huge amounts of data generated by healthcare transactions are too complex and
      voluminous to be processed and analyzed by traditional methods. Data mining
      provides the methodology and technology to transform these mounds of data into
      useful information for decision making. This article explores data mining
      applications in healthcare. In particular, it discusses data mining and its
      applications within healthcare in major areas such as the evaluation of treatment
      effectiveness, management of healthcare, customer relationship management, and
      the detection of fraud and abuse. It also gives an illustrative example of a
      healthcare data mining application involving the identification of risk factors
      associated with the onset of diabetes. Finally, the article highlights the
      limitations of data mining and discusses some future directions.

PMID- 15869216
TI  - CIOs' views of HIPAA Security Rule implementation--an application of Q
      methodology.
AB  - The purpose of this study is to uncover the attitudes held by chief information
      officers (CIOs) regarding the implementation of HIPAA's Security Rule. In March
      and April of 2004, five Chicago area CIOs were surveyed and asked to rank 26
      opinion statements that presented possible implementation barriers to the
      Security Rule. Q-methodology, which is a powerful tool in subjective study, was
      employed to identify and categorize the viewpoints of CIOs toward the barriers.
      Two factors (opinion types) that represented two different views--socially
      motivated CIOs and resources-motivated CIOs--regarding the implementation
      barriers were extracted. The study sheds light on the attitudes and perceptions
      of CIOs as they begin rule implementation. Current CIOs can use this information
      as a way to begin to examine what the prevailing attitude may be at their
      institution and, therefore, how to begin building a successful implementation
      strategy.

PMID- 15869217
TI  - The impact of patient-physician Web messaging on provider productivity.
AB  - Patients increasingly want electronic access to providers, but physicians have
      been slow to offer e-access, fearing they will be overwhelmed by unreimbursed
      patient messages. This article reports on efforts to measure how patient-provider
      Web messaging affects physician productivity. To measure productivity,
      researchers analyzed the work of a group of physicians using a secure Web
      messaging system, compared with a control group that did not use the system.
      Results showed that physicians using the electronic media to communicate had
      about a 10 percent increase in productivity. Secure Web messaging's benefits also
      outweigh those of e-mail in increasing productivity and allaying concerns of
      physicians.

PMID- 15869223
TI  - [Marie-Francoise Colliere, an engaged nurse author].

PMID- 15869224
TI  - [First line nursing interviews in psychiatry].

PMID- 15869225
TI  - [Improving the infusion chain].

PMID- 15869226
TI  - [Eating disorders].

PMID- 15869227
TI  - [To young professionals who choose to work with anorexic patients].

PMID- 15869228
TI  - [Risk factors and possible prevention of eating disorders].

PMID- 15869229
TI  - [Nutritional recommendations and dietetic approach to eating disorders].

PMID- 15869230
TI  - [Mental characteristics of patients with eating disorders].

PMID- 15869231
TI  - [For or against therapeutic isolation?].

PMID- 15869232
TI  - [Therapeutic, ambulatory and hospital management of eating disorders].

PMID- 15869233
TI  - [Nutrition support in the anorexic adolescent].

PMID- 15869234
TI  - [Dramatic expression, a proven therapeutic method].

PMID- 15869235
TI  - [Can we prevent eating disorders?].

PMID- 15869236
TI  - [Bibliography elements. Eating disorders].

PMID- 15869237
TI  - [Cardiovascular drugs. 11/12. Oral anticoagulants].

PMID- 15869238
TI  - [Traffic safety and health professionals. 3/6 An always attentive driver].

PMID- 15869239
TI  - [Neonatal diabetes].

PMID- 15869240
TI  - [Discovering diabetes in the child, and then?].

PMID- 15869241
TI  - [Also know how to listen...the parents].

PMID- 15869242
TI  - [Adolescence and diabetes].

PMID- 15869243
TI  - [The dietician encounters difficulties with a newly-diagnosed diabetic].

PMID- 15869244
TI  - [Acceptance of diabetes in the adult: what is the truth?].

PMID- 15869245
TI  - [What is the role of the podiatrist in the discovery of diabetes?].

PMID- 15869247
TI  - [Diabetes in the aged].

PMID- 15869246
TI  - [The diabetic diet, what a story!].

PMID- 15869248
TI  - [What additional ailments for the aged diabetic?].

PMID- 15869249
TI  - Direct introduction of single protein channels and pores into lipid bilayers.
AB  - We have developed a mechanical method for inserting single pores and channels
      into lipid bilayers. A hand-operated hydrogel probe, coated with a layer of
      proteins, is mechanically engaged with the lipid bilayer. The two major classes
      of membrane proteins (beta barrels and alpha-helix bundles) that can be inserted,
      thereby demonstrating the wide applicability of the approach. Recordings from the
      proteins show that they retain electrical properties that are the same as those
      of proteins inserted from solution. Protein-loaded probes can be used repeatedly,
      allowing individual pores to be rapidly screened one at a time. The method has
      implications for fundamental studies of cell membranes, array fabrication, and
      chemical screening.

PMID- 15869250
TI  - Remote asymmetric induction in an intramolecular ionic Diels-Alder reaction:
      application to the total synthesis of (+)-dihydrocompactin.
AB  - The total synthesis of (+)-dihydrocompactin via an intramolecular ionic Diels
      Alder reaction that proceeds with remote stereocontrol is described. This
      reaction proceeds by an intermediate vinyl-oxocarbenium ion (6), the
      conformational constraints of which lead to the observed asymmetric induction.
      The sense of asymmetric induction appears contrasteric and is explained by the
      proposed reactive conformation shown in Figure 1.

PMID- 15869251
TI  - Hydrogen storage in the dehydrated prussian blue analogues M3[Co(CN)6]2 (M = Mn,
      Fe, Co, Ni, Cu, Zn).
AB  - The porosity and hydrogen storage properties for the dehydrated Prussian blue
      analogues M3[Co(CN)6]2 (M = Mn, Fe, Co, Ni, Cu, Zn) are reported. Argon sorption
      isotherms measured at 87 K afford BET surface areas ranging from 560 m2/g for
      Ni3[Co(CN)6]2 to 870 m2/g for Mn3[Co(CN)6]2; the latter value is comparable to
      the highest surface area reported for any known zeolite. All six compounds show
      significant hydrogen sorption at 77 K and 890 Torr, varying from 1.4 wt % and
      0.018 kg H2/L for Zn3[Co(CN)6]2 to 1.8 wt % and 0.025 kg H2/L for Cu3[Co(CN)6]2.
      Fits to the sorption data employing the Langmuir-Freundlich equation give maximum
      uptake quantities, resulting in a predicted storage capacity of 2.1 wt % and
      0.029 kg H2/L for Cu3[Co(CN)6]2 at saturation. Enthalpies of adsorption for the
      frameworks were calculated from hydrogen isotherms measured at 77 and 87 K and
      found to increase with M varying in the order Mn < Zn < Fe < Co < Cu < Ni. In all
      cases, the binding enthalpies, which lie in the range of 5.3-7.4 kJ/mol, are
      higher than the 4.7-5.2 kJ/mol measured for Zn4O(1,4-benzenedicarboxylate)3.

PMID- 15869252
TI  - Streptavidin as a macroinitiator for polymerization: in situ protein-polymer
      conjugate formation.
AB  - This communication reports the first example of polymerization initiated from
      specific domains on proteins. Streptavidin was coupled with a biotinylated
      initiator for atom transfer radical polymerization (ATRP) and exposed to an
      aqueous solution of CuBr/2,2'-bipyridine and monomer. N-Isopropylacrylamide
      (NIPAAm) and poly(ethylene glycol) methyl ether methacrylate (PEGMA) were readily
      initiated by the modified streptavidin and polymerized from the protein at room
      temperature. Formation of streptavidin-polymer conjugates was confirmed by size
      exclusion chromatography (SEC) and gel electrophoresis. Polymer identity and
      biotinylation was verified using 1H NMR spectroscopy, gel permeation
      chromatography (GPC), and surface plasmon resonance (SPR) after dissociation of
      the biotin-streptavidin complex. This general approach is likely to be extended
      to other proteins and monomers and promises to enable easy synthesis and
      purification of a variety of polymer-protein conjugates.

PMID- 15869253
TI  - Square nets of tellurium: rare-earth dependent variation in the charge-density
      wave of RETe3 (RE = rare-earth element).
AB  - The distortions in the square tellurium nets long known to exist in the
      structures of the charge-density wave materials, RETe3, have been elucidated. The
      (Te2)1- nets contain polytelluride oligomers which propagate in a fashion
      incommensurate from the adjacent (RETe)+ sublattice. The new information sets the
      stage for a much deeper understanding of these systems.

PMID- 15869254
TI  - Polymorphs with varying platinum(II)-thallium(I) interactions.
AB  - TlI[(C4H9N4)PtII(CN)2] forms a red, crystalline polymorph in which the ions are
      arranged to form an extended ...Pt...Tl...Pt...Tl... chain (Pt...Tl distance,
      3.0978(2) A; Pt-Tl-Pt and Tl-Pt-Tl angles, (171.37(2) degrees ) and a yellow
      polymorph in which dimers are connected by pairs of Pt...Tl interactions with a
      Pt...Tl distance of 3.0256(5) A.

PMID- 15869256
TI  - Selective detection of cysteine and glutathione using gold nanorods.
AB  - A unique strategy for the selective detection of micromolar concentrations of
      cysteine/glutathione in the presence of various other alpha-amino acids through
      the plasmon coupling of Au nanorods is reported.

PMID- 15869255
TI  - Fluorescent sensing and selective Pb(II) extraction by a dansylamide ion
      exchanger.
AB  - The (bis)dansylated sulfonamide 1,2-C6H4(NHSO2C10H6-5-N(CH3)2)2 (1) extracted
      Pb(II) selectively from water into 1,2-dichloroethane via an ion-exchange
      mechanism and showed fluorescence quenching upon Pb(II) extraction. The
      distribution ratios for metal extraction (determined by ICP-MS) for Pb(II) were
      133-1410 times higher than those for other metal cations [Co(II), Ni(II), Cu(II),
      Zn(II), and Cd(II)] under identical conditions. Fluorescence quenching was
      observed upon Pb(II) extraction, which was dependent on Pb(II) concentration. The
      monodansylated control, C6H5NHSO2C10H6-5-N(CH3)2 (2), showed neither extraction
      nor quenching, indicating that the fluorescence effects are a direct result of Pb
      coordination to 1. The observed selectivity for Pb(II) is ascribed to the
      formation of a low-coordinate binary Pb(II)-Sulfonamido complex in the organic
      phase.

PMID- 15869257
TI  - Influence of N-methylation on a cation-pi interaction produces a remarkably
      stable beta-hairpin peptide.
AB  - The methylation of lysine in histone tails is a common posttranslational
      modification that functions in histone-regulated chromatin condensation, with
      binding of methylated lysine occurring in aromatic pockets on chromodomain
      proteins. We have synthesized a highly stable 12-residue beta-hairpin peptide
      that exploits the histone-related cation-pi interaction between a methylated
      lysine residue and a tryptophan residue. Thermodynamic analysis reveals
      significant entropic stabilization of the peptide due to methylation of the
      lysine residue. Chemical denaturation of the peptide demonstrates two-state
      behavior. In comparison to other reported, highly stable designed beta-hairpins,
      this peptide is the most thermally stable beta-hairpin reported to date. This
      study provides insight into the role of Lys methylation in histone proteins and
      more generally in mediating protein-protein interactions.

PMID- 15869258
TI  - A highly stable quadruply hydrogen-bonded heterocomplex useful for supramolecular
      polymer blends.
AB  - The butyl urea of guanosine (UG) presents an ADDA hydrogen-bonding array that is
      complementary to the DAAD array of 2,7-diamido-1,8-naphthyridine (DAN). The
      stability of the DAN.UG complex was measured by fluorimetry using the
      fluorescence resonance energy transfer (FRET) from the naphthyridine ring to a
      coumarin 343 moiety linked covalently to the UG unit. The quadruply hydrogen
      bonded complex is extremely stable with a measured association constant, Kassoc,
      of 3 x 108 M-1. Unlike related hydrogen-bonding modules, the guanosine urea, UG,
      contains a relatively fixed tautomeric form and only weakly self-associates
      (Kdimer = ca. 200 M-1). The DAN unit was linked to a styrene-based monomer and
      copolymerized with styrene to form a polymer (PS-DAN) containing a controlled
      number of the DAAD recognition units. Likewise, a methacrylate monomer containing
      the UG unit was copolymerized with butyl methacrylate to form a polymer (PBMA
      UG). Blends formed from PS-DAN and PBMA-UG were characterized by DSC, SEC, and
      viscometry. The importance of selective heterocomplexation and weak self
      association in forming the blended networks was demonstrated by using a
      ureidopyrimidinone (UPy) unit, which also forms strong heterocomplexes with DAN
      but is able to strongly self-associate.

PMID- 15869259
TI  - Fluorescence detection of DNA by the catalytic activation of an aptamer/thrombin
      complex.
AB  - A conjugate consisting of a thrombin aptamer tethered to the thrombin, Th, with a
      sensing nucleic acid (1) is used for the optical detection of DNA. The
      thrombin/aptamer complex blocks the biocatalytic functions of Th. Hybridization
      of the analyte DNA (2) to the sensing nucleic acid 1 yields a rigid duplex that
      detaches the aptamer from Th, a process that activates the protein toward the
      hydrolysis of bis(p-tosyl-Gly-Pro-Arg)-R110 (3) to the rhodamine 110 fluorophore
      (4). The system allows the DNA sensing with a sensitivity limit of 1 x 10-8 M.
      The aptamer/Th conjugate is also immobilized on glass slides for the optical
      detection of DNA. The dissociation of the aptamer/Th complex upon hybridization
      and the subsequent dehybridization of the duplex and the regeneration of the
      catalytically inactive Th/aptamer complex duplicate machinery functions.

PMID- 15869260
TI  - Effect of microstructure on molecular oxygen permeation through condensed
      phospholipid monolayers.
AB  - A method is presented that allows novel measurement of the effect of
      microstructure on the oxygen permeability of highly condensed, polycrystalline
      phospholipid monolayers. Oxygen permeability of the polycrystalline shell coating
      a stationary microbubble is measured directly using an apposing microelectrode in
      the induced transfer mode and modeling oxygen flux through the shell and
      intervening aqueous medium. Varying cooling rate through the phospholipid main
      phase transition permits control of shell microstructure by manipulation of
      crystalline domain size and shape. Domain boundary density, defined as the ratio
      of the mean domain perimeter to the mean domain area, of the microbubble shell is
      determined by fluorescence microscopy. Oxygen permeability was shown to increase
      linearly with domain boundary density at a constant phospholipid acyl chain
      length and, accordingly, was shown to decrease exponentially with increasing
      chain length at a constant domain boundary density. Modification of the energy
      barrier theory to account for microstructural effects, in terms of the domain
      boundary density, provides a general equation to model passive transport through
      polycrystalline monolayer films. Results from this method show promise in
      determining the gas transport kinetics of medical microbubbles and the gas
      exchange characteristics of biological monolayers.

PMID- 15869261
TI  - Dilution-induced spheres-to-vesicles morphological transition in micelles from
      block copolymer/surfactant complexes.
AB  - Metastable spherical micelles have been obtained by mixing in chloroform
      poly(styrene)-block-poly(4-vinylpyridine) diblock copolymers with perfluorinated
      surfactants bearing a carboxylic acid head. Dilution of these initial micelles
      triggers a morphological reorganization resulting in the formation of more stable
      vesicles. This transition can be advantageously used to encapsulate molecules of
      interest.

PMID- 15869262
TI  - Synthetic ion channels with rigid-rod pi-stack architecture that open in response
      to charge-transfer complex formation.
AB  - We describe the design, synthesis, and evaluation of synthetic ion channels with
      a new rigid-rod pi-stack architecture that open in response to guest binding by
      aromatic electron donor-acceptor interactions. Highly cooperative and highly
      selective ligand gating is shown to yield anion selective, small ion channels
      that have the characteristic plum color of the charge-transfer complexes formed
      between the dialkoxynaphthalene ligands and the stacked naphthalenediimide
      acceptors of the channel.

PMID- 15869263
TI  - Transition metal-catalyzed intermolecular [5+2] and [5+2+1] cycloadditions of
      allenes and vinylcyclopropanes.
AB  - Initial examples of the intermolecular Rh(I)-catalyzed [5+2] cycloaddition
      reaction of bifunctional allenes and vinylcyclopropanes are described. The
      reactions proceed with facility and in yields of up to 99% with a variety of
      alkyne-, ester-, styrene-, or cyano-substituents on the allene to afford the
      corresponding cycloadducts. In the presence of CO, the reaction proceeds to an
      eight-membered ring cycloadduct and its transannularly closed product, providing
      the first example of a three-component [5+2+1] cycloaddition with allenes.

PMID- 15869264
TI  - Toward understanding how the lactone moiety of discodermolide affects activity.
AB  - A series of simplified discodermolide analogues have been designed and
      synthesized in an attempt to understand the role of the lactone ring. These
      synthetic efforts have led to an unsubstituted butyrolactone 9 being generated,
      which shows improved activity over the natural product.

PMID- 15869265
TI  - Controllable fabrication of carbon nanotube and nanobelt with a polyoxometalate
      assisted mild hydrothermal process.
AB  - Carbon nanotubes, carbon nanobelts, and carbon nanoparticles can be prepared
      directly from active carbon powders by a polyoxometalates (POMs)-assisted mild
      hydrothermal process. After the hydrothermal reaction the POMs are changed into
      heteropoly blues, which can be converted into the POMs by a small amount of H2O2
      solution.

PMID- 15869266
TI  - Unexpected subtilisin-catalyzed hydrolysis of a sulfinamide bond in preference to
      a carboxamide bond in N-acyl sulfinamides.
AB  - Subtilisin Carlsberg-catalyzed hydrolysis of N-chloroacetyl p-toluenesulfinamide
      favored cleavage of the sulfinamide (S(O)-N) bond with a minor amount (
      approximately 25%) of the expected carboxamide (C(O)-N) bond. The sulfinamide
      hydrolysis was enantioselective (E approximately 17) and yielded remaining
      starting material enriched in the R-enantiomer and achiral product, sulfinic acid
      and chloroacetamide, as confirmed by mass spectra and NMR. In contrast, the
      related subtilisin BPN' and E favored the carboxamide hydrolysis. Hydrolysis of
      the pseudo-symmetrical N-p-toluoyl p-toluenesulfinamide, which contains a
      sulfinamide and a carboxamide in similar steric and electronic environments, gave
      only sulfinamide cleavage (>10:1) for subtilisin Carlsberg, showing that
      sulfinamide cleavage is the preferred path even when a similar carboxamide is
      available.

PMID- 15869267
TI  - Thermally gated liposomes.
AB  - The combined use of a pore-forming amphiphile, 1 (derived from lysine, cholic
      acid, and spermine), and thermally sensitive liposomes (made from 1,2-dipalmitoyl
      sn-glycero-3-phosphocholine, DPPC) to create "thermally gated liposomes" (TGLs)
      has been demonstrated. Thus, at temperatures that lie above the gel to liquid
      crystalline phase transition temperature of DPPC (i.e., 41 degrees C), 1 creates
      pores within DPPC membranes through which entrapped aqueous solutes, such as
      carboxyfluorescein, can readily pass. Below this temperature, efflux rates are
      greatly reduced. The potential of TGLs as devices for the targeted delivery of
      therapeutic agents is briefly discussed.

PMID- 15869268
TI  - Direct electrochemical regeneration of monooxygenase subunits for biocatalytic
      asymmetric epoxidation.
AB  - We report the first example of direct electrochemical regeneration of a flavin
      dependent monooxygenase for asymmetric epoxidation catalysis. It is shown that
      electrochemical regeneration of the oxygenase subunit of the multicomponent
      styrene monooxygenase is sufficient to perform enantiospecific S-epoxidation of
      various styrene derivatives. Kinetic bottlenecks of the novel electroenzymatic
      reaction are identified. This work opens up new alternatives for asymmetric
      oxyfunctionalization catalysis.

PMID- 15869269
TI  - Evidence for lower critical solution behavior in ionic liquid solutions.
AB  - Lower critical solution temperatures (LCST)-type of phase diagrams, including the
      presence of closed loops, have been encountered for the first time in binary and
      quasi-binary liquid solutions of ionic liquids. Furthermore, the results
      constitute the first experimental support for the existence of a theoretically
      postulated, but never encountered, special kind of type VII phase diagram. Two
      distinct mechanisms are involved in the appearance of demixing upon temperature
      increase. These findings underlie the presence of specific, oriented interactions
      between the ionic liquid, 1-alkyl-3-methylimidazolium
      bis{(trifluoromethyl)sulfonyl}amide, [Cnmim][NTf2], and trichloromethane, as well
      as aggregation phenomena.

PMID- 15869270
TI  - Can decarbonylation of acyl radicals be overcome in radical addition reactions?
      En route to a solution employing N-acyl oxazolidinones and SmI2/H2O.
AB  - The application of acyl radicals in radical addition reactions in the absence of
      a CO atmosphere is generally limited to aryl or alpha-unsubstituted alkyl acyl
      radicals due to competing decarbonylations where the rate constant for this
      degradation process surpasses 104 s-1. In this work, a potential solution to
      avoid the problem of decarbonylations is presented employing N-acyl
      oxazolidinones which are reduced to acyl radical equivalents in the presence of
      samarium diiodide and water. In the company of an acrylamide, acrylate, or
      acrylonitrile, the product from a formal acyl radical addition is obtained in
      yields up to 87%. Examples are given where the decarbonylation rate constants
      even exceed 108 s-1. It is proposed that the reaction proceeds via a ketyl-like
      intermediate.

PMID- 15869271
TI  - Enzymatic lithography of phospholipid bilayer films by stereoselective
      hydrolysis.
AB  - The stereoselective phospholipase A2-catalyzed hydrolysis of patterned
      phospholipid bilayers consisting of the l- and d-isomers of alpha
      dilauroylphosphatidylcholine (DLPC) and alpha-dipalmitoylphosphatidylcholine
      (DPPC) is reported. The stereochemically directed enzyme lithography demonstrated
      herein allows the parallel modification of large surface areas and constitutes a
      potentially useful method to structure biomimetic films, given the stereospecific
      action of many enzymes.

PMID- 15869272
TI  - Metal-peroxo versus metal-oxo oxidants in non-heme iron-catalyzed olefin
      oxidations: computational and experimental studies on the effect of water.
AB  - Computational and experimental studies show that Fe(BPMEN)-catalyzed olefin
      oxidation has two (FeIII-OOH and FeV=O) oxidant species, which act with
      comparable activation barriers. The presence of water favors formation of an HO
      FeV=O oxidant via water-assisted O-OH bond cleavage and leads to both epoxide and
      cis-diol products. In the absence of water, the oxidant is the FeIII-OOH [or
      (MeCN)FeIII-OOH], and oxidation mainly leads to epoxide. This conclusion differs
      from that derived from DFT investigations of iron-porphyrin-catalyzed olefin
      epoxidation, where the FeIII-OOH pathway is deemed too high in energy to be
      plausible. The difference between these two systems may lie in the more flexible
      coordination environment of the non-heme iron complex, which has an available
      adjacent coordination site that contributes to the activation of the peroxide in
      both wa and nwa pathways.

PMID- 15869273
TI  - Thiolate ligands for synthesis of water-soluble gold clusters.
AB  - Water-soluble monolayer-protected gold clusters (MPCs) have been an object of
      investigation by many research groups since their first syntheses were reported
      in 1998 and 1999. The basic requirements for a ligand to form a monolayer
      protecting a gold cluster were established some time ago for alkanethiolate MPCs,
      but there has been no such information published for water-soluble MPCs. We
      identify 6 new ligands capable of forming water-soluble MPCs, as well as 22 water
      soluble ligands that fail to form MPCs. Our findings contribute not only to the
      definition of the requirements for MPC formation but also to the variety of MPCs
      available for applications in chemistry and biology.

PMID- 15869274
TI  - Fluorination and electrical conductivity of BN nanotubes.
AB  - Fluorination of BN nanotubes has been performed using a catalytic growth method,
      which leads to the appearance of markedly curved fluorine-doped BN sheets and
      converts originally insulating BN nanotubes to semiconductors, as confirmed by
      the comparative electron transport four-probe measurements on doped and undoped
      individual BN nanotubes.

PMID- 15869275
TI  - Effects of rotational symmetry order on the solid state dynamics of phenylene and
      diamantane rotators.
AB  - The rotational dynamics of phenylene and diamantane rotators in crystals of 1,9
      bis(4-[3,3,3-triphenylpropynyl]phenyl)diamantane were analyzed independently
      within the same crystal structure. The dynamics of phenylene rotation were
      established by dynamic line shape analysis using 13C CPMAS NMR. The phenylene
      signals were selectively highlighted by deuteration of the aromatic trityls and
      the use of short contact times for cross polarization. The dynamics of the
      diamantane group were established by 1H spin-lattice relaxation under conditions
      where dipolar relaxation was shown to be the dominant mechanism between 250 and
      425 K. A factor of 20 000 between the rates of rotation of the faster diamantane
      and the slower phenylene at 300 K supports expectations that higher symmetry
      rotors should have significantly faster dynamics.

PMID- 15869276
TI  - Coordinated design of cofactor and active site structures in development of new
      protein catalysts.
AB  - New methods for the synthesis of artificial metalloenzymes are important for the
      construction of novel biocatalysts and biomaterials. Recently, we reported new
      methodology for the synthesis of artificial metalloenzymes by reconstituting apo
      myoglobin with metal complexes (Ohashi, M. et al., Angew Chem., Int. Ed. 2003,
      42, 1005-1008). However, it has been difficult to improve their reactivity, since
      their crystal structures were not available. In this article, we report the
      crystal structures of M(III)(Schiff base).apo-A71GMbs (M = Cr and Mn). The
      structures suggest that the position of the metal complex in apo-Mb is regulated
      by (i) noncovalent interaction between the ligand and surrounding peptides and
      (ii) the ligation of the metal ion to proximal histidine (His93). In addition, it
      is proposed that specific interactions of Ile107 with 3- and 3'-substituent
      groups on the salen ligand control the location of the Schiff base ligand in the
      active site. On the basis of these results, we have successfully controlled the
      enantioselectivity in the sulfoxidation of thioanisole by changing the size of
      substituents at the 3 and 3' positions. This is the first example of an
      enantioselective enzymatic reaction regulated by the design of metal complex in
      the protein active site.

PMID- 15869277
TI  - Structural mimicry of two cytochrome b(562) interhelical loops using macrocycles
      constrained by oxazoles and thiazoles.
AB  - A major chemical challenge is the structural mimicry of discontinuous protein
      surfaces brought into close proximity through polypeptide folding. We report the
      design, synthesis, and solution structure of a highly functionalized saddle
      shaped macrocyclic scaffold, constrained by oxazoles and thiazoles, supporting
      two short peptide loops projecting orthogonally from the same face of the
      scaffold. This structural mimetic of two interhelical loops of cytochrome b(562)
      illustrates a promising approach to structurally mimicking discontinuous loops of
      proteins.

PMID- 15869278
TI  - Laser flash photolysis generation and kinetic studies of porphyrin-manganese-oxo
      intermediates. Rate constants for oxidations effected by porphyrin-Mn(V)-oxo
      species and apparent disproportionation equilibrium constants for porphyrin
      Mn(IV)-oxo species.
AB  - Porphyrin-manganese(V)-oxo and porphyrin-manganese(IV)-oxo species were produced
      in organic solvents by laser flash photolysis (LFP) of the corresponding
      porphyrin-manganese(III) perchlorate and chlorate complexes, respectively,
      permitting direct kinetic studies. The porphyrin systems studied were 5,10,15,20
      tetraphenylporphyrin (TPP), 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin
      (TPFPP), and 5,10,15,20-tetrakis(4-methylpyridinium)porphyrin (TMPyP). The order
      of reactivity for (porphyrin)Mn(V)(O) derivatives in self-decay reactions in
      acetonitrile and in oxidations of substrates was (TPFPP) > (TMPyP) > (TPP).
      Representative rate constants for reaction of (TPFPP)Mn(V)(O) in acetonitrile are
      k = 6.1 x 10(5) M(-1) s(-1) for cis-stilbene and k = 1.4 x 10(5) M(-1) s(-1) for
      diphenylmethane, and the kinetic isotope effect in oxidation of ethylbenzene and
      ethylbenzene-d(10) is k(H)/k(D) = 2.3. Competitive oxidation reactions conducted
      under catalytic conditions display approximately the same relative rate constants
      as were found in the LFP studies of (porphyrin)Mn(V)(O) derivatives. The apparent
      rate constants for reactions of (porphyrin)Mn(IV)(O) species show inverted
      reactivity order with (TPFPP) < (TMPyP) < (TPP) in reactions with cis-stilbene,
      triphenylamine, and triphenylphosphine. The inverted reactivity results because
      (porphyrin)Mn(IV)(O) disproportionates to (porphyrin)Mn(III)X and
      (porphyrin)Mn(V)(O), which is the primary oxidant, and the equilibrium constants
      for disproportionation of (porphyrin)Mn(IV)(O) are in the order (TPFPP) < (TMPyP)
      < (TPP). The fast comproportionation reaction of (TPFPP)Mn(V)(O) with
      (TPFPP)Mn(III)Cl to give (TPFPP)Mn(IV)(O) (k = 5 x 10(8) M(-1) s(-1)) and
      disproportionation reaction of (TPP)Mn(IV)(O) to give (TPP)Mn(V)(O) and
      (TPP)Mn(III)X (k approximately 2.5 x 10(9) M(-1) s(-1)) were observed. The
      relative populations of (porphyrin)Mn(V)(O) and (porphyrin)Mn(IV)(O) were
      determined from the ratios of observed rate constants for self-decay reactions in
      acetonitrile and oxidation reactions of cis-stilbene by the two oxo derivatives,
      and apparent disproportionation equilibrium constants for the three systems in
      acetonitrile were estimated. A model for oxidations under catalytic conditions is
      presented.

PMID- 15869279
TI  - Pairwise decomposition of residue interaction energies using semiempirical
      quantum mechanical methods in studies of protein-ligand interaction.
AB  - Pairwise decomposition of the interaction energy between molecules is shown to be
      a powerful tool that can increase our understanding of macromolecular recognition
      processes. Herein we calculate the pairwise decomposition of the interaction
      energy between the protein human carbonic anhydrase II (HCAII) and the fluorine
      substituted ligand N-(4-sulfamylbenzoyl)benzylamine (SBB) using semiempirical
      quantum mechanics based methods. We dissect the interaction between the ligand
      and the protein by dividing the ligand and the protein into subsystems to
      understand the structure-activity relationships as a result of fluorine
      substitution. In particular, the off-diagonal elements of the Fock matrix that is
      composed of the interaction between the ionic core and the valence electrons and
      the exchange energy between the subsystems or atoms of interest is examined in
      detail. Our analysis reveals that the fluorine-substituted benzylamine group of
      SBB does not directly affect the binding energy. Rather, we find that the
      strength of the interaction between Thr199 of HCAII and the sulfamylbenzoyl group
      of SBB affects the binding affinity between the protein and the ligand. These
      observations underline the importance of the sulfonamide group in binding
      affinity as shown by previous experiments (Maren, T. H.; Wiley: C. E. J. Med.
      Chem. 1968, 11, 228-232). Moreover, our calculations qualitatively agree with the
      structural aspects of these protein-ligand complexes as determined by X-ray
      crystallography.

PMID- 15869280
TI  - The mechanism of activation of a [NiFe]-hydrogenase by electrons, hydrogen, and
      carbon monoxide.
AB  - Activation of the oxidized inactive state (termed Unready or Ni(u)) of the [NiFe]
      hydrogenase from Allochromatium vinosum requires removal of an unidentified
      oxidizing entity [O], produced by partial reduction of O(2). Dynamic
      electrochemical kinetic studies, subjecting enzyme molecules on an electrode to
      sequences of potential steps and gas injections, establish the order of events in
      an otherwise complex sequence of reactions that involves more than one
      intermediate retaining [O] or its redox equivalent; fast and reversible electron
      transfer precedes the rate-determining step which is followed by a reaction with
      H(2), or the inhibitor CO, that renders the reductive activation process
      irreversible.

PMID- 15869281
TI  - Direct ESR detection of pentadienyl radicals and peroxyl radicals in lipid
      peroxidation: mechanistic insight into regioselective oxygenation in
      lipoxygenases.
AB  - Well-resolved ESR spectra of free pentadienyl radicals have been observed under
      photoirradiation of di-tert-butylperoxide (Bu(t)OOBu(t)) and polyunsaturated
      fatty acids in the absence of O(2), allowing us to determine the hfc values. The
      hfc values of linoleyl radical indicate that the spin density is the largest at
      the C-11 position. The linoleyl radical is readily trapped by O(2) to produce the
      peroxyl radical (11-HPO.) in which O(2) is added mainly at the C-11 position of
      the pentadienyl radical as indicated by the comparison of the ESR spectra of
      peroxyl radicals derived from linoleic acid and [11,11-(2)H(2)]linoleic acid. The
      peroxyl radical (13-HPO.), which is initially formed by the hydrogen abstraction
      from 13-(S)-hydroperoxy-9(Z),11(E)-octadecadienoic acid (13-HPOD) by Bu(t)O., is
      found to isomerize to 11-HPO. via removal of O(2) from 13-HPO. and addition of
      O(2) to linoleyl radical to produce 11-HPO. . This finding supports an idea of
      O(2) entering via a specific protein channel, which determines the stereo- and
      regiochemistry of the biradical combination between O(2) and linoleyl radical in
      lipoxygenases.

PMID- 15869282
TI  - Molecular insight into the electrostatic membrane surface potential by 14n/31p
      MAS NMR spectroscopy: nociceptin-lipid association.
AB  - Exploiting naturally abundant (14)N and (31)P nuclei by high-resolution MAS NMR
      (magic angle spinning nuclear magnetic resonance) provides a molecular view of
      the electrostatic potential present at the surface of biological model membranes,
      the electrostatic charge distribution across the membrane interface, and changes
      that occur upon peptide association. The spectral resolution in (31)P and (14)N
      MAS NMR spectra is sufficient to probe directly the negatively charged phosphate
      and positively charged choline segment of the electrostatic P(-)-O-CH(2)-CH(2)
      N(+)(CH(3))(3) headgroup dipole of zwitterionic DMPC
      (dimyristoylphosphatidylcholine) in mixed-lipid systems. The isotropic shifts
      report on the size of the potential existing at the phosphate and ammonium group
      within the lipid headgroup while the chemical shielding anisotropy ((31)P) and
      anisotropic quadrupolar interaction ((14)N) characterize changes in headgroup
      orientation in response to surface potential. The (31)P/(14)N isotropic chemical
      shifts for DMPC show opposing systematic changes in response to changing membrane
      potential, reflecting the size of the electrostatic potential at opposing ends of
      the P(-)-N(+) dipole. The orientational response of the DMPC lipid headgroup to
      electrostatic surface variations is visible in the anisotropic features of (14)N
      and (31)P NMR spectra. These features are analyzed in terms of a modified
      "molecular voltmeter" model, with changes in dynamic averaging reflecting the
      tilt of the C(beta)-N(+)(CH)(3) choline and PO(4)(-) segment. These properties
      have been exploited to characterize the changes in surface potential upon the
      binding of nociceptin to negatively charged membranes, a process assumed to
      proceed its agonistic binding to its opoid G-protein coupled receptor.

PMID- 15869283
TI  - Dynamic behavior of chiral sulfonimidoyl-substituted allyl and alkyl
      (dimethylamino)titanium(IV) complexes: metallotropic shift, reversible beta
      hydride elimination/reinsertion, and ab initio calculations of allyl and alkyl
      aminosulfoxonium ylides.
AB  - Variable-temperature (1)H and (13)C NMR spectroscopy of the sulfonimidoyl
      substituted allyltitanium(IV) complexes E-1a-c and Z-1a-c, which carry
      diethylamino groups at the Ti atom, revealed a fast 1,3-C,N-shift of the Ti atom,
      leading to an equilibrium between the epimeric Calpha-titanium allyl complexes A
      and C and the N-titanium allyl aminosulfoxonium ylide B. Based on these findings
      a model for the reactions of E-1a-c and Z-1a-c with aldehydes is proposed, which
      features regio- and diastereoselective reactions of the N-titanium ylide B at the
      alpha-position and the Calpha-titanium complex A at the gamma-position. Model ab
      initio calculations of the methylene and allyl (dimethylamino)sulfoxonium ylides
      10 and 14, respectively, revealed short Calpha-S bonds, a stabilization by both
      electrostatic interaction and negative hyperconjugation, and a low Calpha-S
      rotational barrier. The ylides preferentially adopt Calpha-S and Calpha-N
      conformations in which the lone pair orbital at the Calpha atom is periplanar to
      the S=O bond and that at the N atom periplanar to the Calpha-Ph bond. Variable
      temperature NMR spectroscopy of the sulfonimidoyl-substituted alkyltitanium(IV)
      complex 16, which carries diethylamino groups at the Ti atom, revealed a dynamic
      behavior leading to a complete topomerization of all four methylene hydrogens of
      the Calpha-ethyl groups. Two fast processes are held responsible for the
      topomerization of the hydrogens of 16. The first one is a reversible
      intramolecular beta-hydride elimination/alkene-Ti-H insertion with the
      intermediate formation of a complex between (Et(2)N)TiH and a 1-alkenyl
      sulfoximine, and the second one consists of a reversible 1,3-C,N-shift of the Ti
      atom in combination with a Calpha-S bond rotation. Interestingly, the room
      temperature NMR spectra of the corresponding sulfonimidoyl-substituted
      alkyltitanium(IV) complex 17, which carries isopropoxy groups at the Ti atom,
      give no indication of a similar dynamic behavior of this complex.

PMID- 15869284
TI  - Heterogeneously catalyzed aerobic oxidative biaryl coupling of 2-naphthols and
      substituted phenols in water.
AB  - The oxidative coupling reaction can efficiently be promoted by supported
      ruthenium catalyst Ru(OH)x/Al2O3. A variety of 2-naphthols and substituted
      phenols can be converted to the corresponding biaryl compounds in moderate to
      excellent yields using molecular oxygen as a sole oxidant in water without any
      additives. The catalysis is truly heterogeneous in nature, and Ru(OH)x/Al2O3 can
      easily be recovered after the reaction. The catalyst can be recycled seven times
      with the maintenance of the catalytic performance, and the total turnover number
      reaches up to 160. The results of competitive coupling reactions suggest that the
      present oxidative biaryl coupling reaction proceeds via the homolytic coupling of
      two radical species and the Ru(OH)x/Al2O3 catalyst acts as an one-electron
      oxidant. Two radical species are coupled to give the corresponding biaryl
      product, and the one-electron reduced catalyst is reoxidized by molecular oxygen.
      The amounts of O(2) uptake and H(2)O formation were almost one-quarter and one
      half the amount of substrate consumed, respectively, supporting the reaction
      mechanism. The kinetic data and kinetic isotope effect show that the reoxidation
      of the reduced catalyst is the rate-limiting step for the coupling reaction.

PMID- 15869285
TI  - Mechanochromism of piroxicam accompanied by intermolecular proton transfer probed
      by spectroscopic methods and solid-phase changes.
AB  - Structural and solid-state changes of piroxicam in its crystalline form under
      mechanical stress were investigated using cryogenic grinding, powder X-ray
      diffractometry, diffuse-reflectance solid-state ultraviolet-visible spectroscopy,
      variable-temperature solid-state (13)C nuclear magnetic resonance spectroscopy,
      and solid-state diffuse-reflectance infrared Fourier transform spectroscopy.
      Crystalline piroxicam anhydrate exists as colorless single crystals irrespective
      of the polymorphic form and contains neutral piroxicam molecules. Under
      mechanical stress, these crystals become yellow amorphous piroxicam, which has a
      strong propensity to recrystallize to a colorless crystalline phase. The yellow
      color of amorphous piroxicam is attributed to charged piroxicam molecules.
      Variable-temperature solid-state (13)C NMR spectroscopy indicates that most of
      the amorphous piroxicam consists of neutral piroxicam molecules; the charged
      species comprise only about 8% of the amorphous phase. This ability to quantify
      the fractions of charged and neutral molecules of piroxicam in the amorphous
      phase highlights the unique capability of solid-state NMR to quantify mixtures in
      the absence of standards. Other compounds of piroxicam, which are yellow, are
      known to contain zwitterionic piroxicam molecules. The present work describes a
      system in which proton transfer accompanies both solid-state disorder and a
      change in color induced by mechanical stress, a phenomenon which may be termed
      mechanochromism of piroxicam.

PMID- 15869286
TI  - Mechanistic studies on the cyclization of (Z)-1,2,4-heptatrien-6-yne in methanol:
      a possible nonadiabatic thermal reaction.
AB  - Myers et al. pyrolyzed (Z)-1,2,4-heptatrien-6-yne (1) in methanol at 100 degrees
      C and observed benzylmethyl ether (2) as a major product and 2-phenylethanol (3)
      as a minor product. If a biradical intermediate, such as the open-shell singlet
      state of alpha,3-didehydrotoluene (4), was the only intermediate generated by the
      cyclization, then reaction with methanol might be expected to afford 2
      phenylethanol as the principal product. The question that has been of interest
      since its first discovery is the origin of the principal product of the title
      reaction, benzylmethyl ether. This report considers three mechanisms for
      formation of the benzylmethyl ether: direct methanol participation in the
      cyclization of the reactant, partial ether formation from the biradical 4, or
      involvement of the closed-shell zwitterionic state of alpha,3-didehydrotoluene
      (5). A fourth mechanism, involving a cyclic allene intermediate, has been ruled
      out by earlier studies. In the present work, the first two mechanisms are ruled
      out by experiment and/or calculation. The remaining one, involving the
      zwitterion, is shown to be consistent with experimental and computational data
      only if a component of the reaction follows a nonadiabatic course.

PMID- 15869287
TI  - Potent and selective structure-based dibenzofuran inhibitors of transthyretin
      amyloidogenesis: kinetic stabilization of the native state.
AB  - Transthyretin (TTR) amyloidogenesis requires rate-limiting tetramer dissociation
      and partial monomer denaturation to produce a misassembly competent species. This
      process has been followed by turbidity to identify transthyretin amyloidogenesis
      inhibitors including dibenzofuran-4,6-dicarboxylic acid (1). An X-ray cocrystal
      structure of TTR.1(2) reveals that it only utilizes the outer portion of the two
      thyroxine binding pockets to bind to and inhibit TTR amyloidogenesis. Herein,
      structure-based design was employed to append aryl substituents at C1 of the
      dibenzofuran ring to complement the unused inner portion of the thyroxine binding
      pockets. Twenty-eight amyloidogenesis inhibitors of increased potency and
      dramatically increased plasma TTR binding selectivity resulted. These function by
      imposing kinetic stabilization on the native tetrameric structure of TTR,
      creating a barrier that is insurmountable under physiological conditions. Since
      kinetic stabilization of the TTR native state by interallelic trans suppression
      is known to ameliorate disease, there is reason to be optimistic that the
      dibenzofuran-based inhibitors will do the same. Preventing the onset of
      amyloidogenesis is the most conservative strategy to intervene clinically, as it
      remains unclear which of the TTR misassembly intermediates results in toxicity.
      The exceptional binding selectivity enables these inhibitors to occupy the
      thyroxine binding site(s) in a complex biological fluid such as blood plasma,
      required for inhibition of amyloidogenesis in humans. It is now established that
      the dibenzofuran-based amyloidogenesis inhibitors have high selectivity,
      affinity, and efficacy and are thus excellent candidates for further
      pharmacologic evaluation.

PMID- 15869288
TI  - Neutron vibrational spectroscopy gives new insights into the structure of poly(p
      phenylene terephthalamide).
AB  - The vibrational spectra of benzanilide and poly(p-phenylene terephthalamide) have
      been measured using inelastic neutron scattering. These compounds have similar
      hydrogen-bond networks, which, for poly(p-phenylene terephthalamide), lead to two
      dimensional hydrogen-bonded sheets in the crystal. Experimental spectra are
      compared with solid-state, quantum chemical calculations based on density
      functional theory (DFT). Such "parameter-free" calculations allow the structure
      dynamics relation in this type of compound to be quantified, which is
      demonstrated here for benzanilide. In the case of poly(p-phenylene
      terephthalamide), vibrational spectroscopy and DFT calculations help resolve long
      standing questions about the packing of hydrogen-bonded sheets in the solid
      state.

PMID- 15869289
TI  - Isotope effects and the nature of enantioselectivity in the shi epoxidation. The
      importance of asynchronicity.
AB  - The epoxidation of beta-methylstyrene catalyzed by the Shi fructose-derived
      ketone is studied using experimental kinetic isotope effects and DFT
      calculations. The observation of a large beta olefinic (13)C isotope effect and
      small alpha carbon isotope effect is indicative of an asynchronous transition
      state with more advanced formation of the C-O bond to the beta olefinic carbon.
      By varying the catalyst conformation and alkene orientation, diverse transition
      structure geometries were located calculationally, and the lowest-energy
      structure leads to an accurate prediction of the isotope effects. Given this
      support for the accuracy of the calculations employed, the nature of
      enantioselectivity in this and related epoxidations is considered. The lowest
      energy transition structures are generally those in which the differential
      formation of the incipient C-O bonds, the "asynchronicity," resembles that of an
      unhindered model, and the imposition of greater or less asynchronicity leads to
      higher barriers. In reactions of cis-disubstituted and terminal alkenes using
      Shi's oxazolidinone catalyst, the asynchronicity of the epoxidation transition
      state leads to increased steric interaction with the oxazolidinone when a pi
      conjugating substituent is distal to the oxazolidinone but decreased steric
      interaction when the pi-conjugating substituent is proximal to the oxazolidinone.
      Overall, the asynchronicity of the transition state must be considered carefully
      to understand the enantioselectivity.

PMID- 15869290
TI  - In situ selection of lead compounds by click chemistry: target-guided
      optimization of acetylcholinesterase inhibitors.
AB  - The target-guided, in situ click chemistry approach to lead discovery has been
      successfully employed for discovering acetylcholinesterase (AChE) inhibitors by
      incubating a selected enzyme/tacrine azide combination with a variety of
      acetylene reagents that were not previously known to interact with the enzyme's
      peripheral binding site. The triazole products, formed by the enzyme, were
      identified by HPLC-mass spectrometry analysis of the crude reaction mixtures. The
      target-guided lead discovery search was also successful when performed with
      reagent mixtures containing up to 10 components. From 23 acetylene reagents, the
      enzyme selected two phenyltetrahydroisoquinoline (PIQ) building blocks that
      combined with the tacrine azide within the active center gorge to form
      multivalent inhibitors that simultaneously associate with the active and
      peripheral binding sites. These new inhibitors are up to 3 times as potent as our
      previous phenylphenanthridinium-derived compounds, and with dissociation
      constants as low as 33 femtomolar, they are the most potent noncovalent AChE
      inhibitors known. In addition, the new compounds lack a permanent positive charge
      and aniline groups and possess fewer fused aromatic rings. Remarkably, despite
      the high binding affinity, the enzyme displayed a surprisingly low preference for
      one PIQ enantiomer over the other.

PMID- 15869291
TI  - A theoretical study of the iminoxyl/oxime self-exchange reaction. A five-center,
      cyclic proton-coupled electron transfer.
AB  - In solution, the self-exchange reactions for oxygen-centered pi-radicals, e.g.,
      PhO. + PhOH <==>PhOH + PhO., are known to occur with low activation enthalpies
      (E(a) approximately equal to 2 kcal/mol). For the PhO./PhOH couple and, we
      conclude, for other O-centered pi-radicals, exchange occurs by proton-coupled
      electron transfer (PCET) with the proton transferred between oxygen electron
      pairs while the electron migrates between oxygen orbitals orthogonal to the -O- -
      -H- - -O- transition state plane (Mayer et al. J. Am. Chem. Soc. 2002, 123,
      11142). Iminoxyls, R(2)C=NO., are sigma-radicals with substantial spin density on
      the nitrogen. The R(2)C=NO./R(2)C=NOH self-exchange has a significant E(a)
      (Mendenhall et al. J. Am. Chem. Soc. 1973, 95, 627). For this exchange, DFT
      calculations have revealed a counterintuitive cisoid transition state in which
      the seven atoms, >C=NO- - -H- - -ON=C<, lie in a plane (R = H, Me) or, for steric
      reasons, two planes twisted at 45.2 degrees (R = Me(3)C). The planar transition
      state has the two N-O dipoles close to each other and pointing in the same
      direction and an O- - -H- - -O angle of 165.4 degrees . A transoid transition
      state for R = H lies 3.4 kcal/mol higher in energy than the cisoid despite a more
      favorable arrangement of the dipoles and a near linear O- - -H- - -O. It is
      concluded that iminoxyl/oxime self-exchange reactions occur by a five-center,
      cyclic PCET mechanism with the proton being transferred between electron pairs on
      the oxygens and the electron migrating between in-plane orbitals on the two
      nitrogens (R(N-N) = 2.65 A). The calculated E(a) values (8.8-9.9 kcal/mol) are in
      satisfactory agreement with the limited experimental data.

PMID- 15869292
TI  - Determination of molecular structure in solution using vibrational circular
      dichroism spectroscopy: the supramolecular tetramer of S-2,2'-dimethyl-biphenyl
      6,6'-dicarboxylic acid.
AB  - The infrared (IR) and vibrational circular dichroism (VCD) spectra of S-2,2'
      dimethyl-biphenyl-6,6'-dicarboxylic acid, S-1, in CDCl(3) solution are
      concentration-dependent, showing that oligomerization occurs with increasing
      concentration. DFT calculations support the conclusion that the oligomer formed
      is the cyclic tetramer (S-1)(4), in which S-1 monomers are linked by hydrogen(H)
      bonded (COOH)(2) moieties. Due to the existence of two inequivalent tautomeric
      conformations of each (COOH)(2) moiety, six inequivalent conformations of (S
      1)(4) are possible. B3LYP/6-31G* DFT calculations predict that the conformation
      "aaab", possessing three equivalent (COOH)(2) conformations, a, and one
      tautomeric conformation, b, has the lowest free energy. B3LYP/6-31G* IR and VCD
      spectra vary substantially with conformation. The B3LYP/6-31G* IR and VCD spectra
      of the C=O stretch modes of "aaab" are in excellent agreement with the
      experimental spectra, while those of all other conformations exhibit poor
      agreement, confirming the prediction that the "aaab" conformation is the
      predominant conformation. Comparison of the calculated IR and VCD spectra of the
      six conformations to the experimental spectra in the range 1100-1600 cm(-1)
      further supports this conclusion. The study is the first to use VCD spectroscopy
      to determine the structure of a supramolecular species.

PMID- 15869293
TI  - Thermal and catalyzed [3,3]-phosphorimidate rearrangements.
AB  - [3,3]-Sigmatropic rearrangements have been widely utilized for the synthesis of
      structurally complex organic molecules because of the ease with which carbon
      carbon bonds are formed in a regio- and stereocontrolled manner. However, there
      are far fewer [3,3]-rearrangements available for the selective formation of
      carbon-nitrogen bonds despite the enormous potential of such reactions for the
      preparation of stereodefined allylic amines. We describe here the scope and
      mechanism of a [3,3]-rearrangement of allylic phosphorimidates that provides
      access to stereodefined allylic amines of diverse structure. The reactive
      intermediate in the reaction, an allylic phosphorimidate, is produced in situ
      through the combination of readily available starting materials (allylic
      alcohols, chlorophosphites, and organic azides), rendering the reaction an
      efficient three-component process. Analogous to other [3,3]-rearrangements, the
      stereochemistry in an allylic alcohol starting material is transferred with
      fidelity to the allylic amine product and, further, allylic amines are produced
      as single olefin isomers. In addition, a crossover experiment indicates that the
      rearrangement is an intramolecular process. Finally, activation of the allylic
      moiety either through incorporation of electron-deficient functional groups or
      through the use of a transition-metal catalyst significantly facilitates the
      reaction and consequently the preparation of a wider range of substitution
      patterns.

PMID- 15869294
TI  - Ultrafast energy-electron transfer cascade in a multichromophoric light
      harvesting molecular square.
AB  - A molecular square with dimensions of about 4 nm, incorporating sixteen pyrene
      chromophores attached to four ditopic bay-functionalized perylene bisimide
      chromophores, has been synthesized by coordination to four Pt(II) phosphine
      corner units and fully characterized via NMR spectroscopy and ESI-FTICR mass
      spectrometry. Steady-state and time-resolved emission as well as femtosecond
      transient absorption studies reveal the presence of a highly efficient (>90%) and
      fast photoinduced energy transfer (k(en) approximately equal to 5.0 x 10(9) s(
      1)) from the pyrene to the perylene bisimide chromophores and a very fast and
      efficient electron transfer (>94%, k(et) approximately equal to 5 x 10(11) up to
      43 x 10(11) s(-1)). Spectrotemporal parametrization indicates upper excited-state
      electron-transfer processes, various energy and electron-transfer pathways, and
      chromophoric heterogeneity. Temperature-dependent time-resolved emission
      spectroscopy has shown that the acceptor emission lifetime increases with
      decreasing temperature from which an electron-transfer barrier is obtained. The
      extremely fast electron-transfer processes (substantially faster and more
      efficient than in the free ligand) that are normally only observed in solid
      materials, together with the closely packed structure of 20 chromophoric units,
      indicate that we can consider the molecular square as a monodisperse
      nanoaggregate: a molecularly defined ensemble of chromophores that partly behaves
      like a solid material.

PMID- 15869295
TI  - Phase transition between nanostructures of titanate and titanium dioxides via
      simple wet-chemical reactions.
AB  - Titanate nanofibers of various sizes and layered structure were prepared from
      inorganic titanium compounds by hydrothermal reactions. These fibers are
      different from "refractory" mineral substances because of their dimension,
      morphology, and significant large ratio of surface to volume, and, surprisingly,
      they are highly reactive. We found, for the first time, that phase transitions
      from the titanate nanostructures to TiO(2) polymorphs take place readily in
      simple wet-chemical processes at temperatures close to ambient temperature. In
      acidic aqueous dispersions, the fibers transform to anatase and rutile
      nanoparticles, respectively, but via different mechanisms. The titanate fibers
      prepared at lower hydrothermal temperatures transform to TiO(2) polymorphs at
      correspondingly lower temperatures because they are thinner, possess a larger
      surface area and more defects, and possess a less rigid crystal structure,
      resulting in lower stability. The transformations are reversible: in this case,
      the obtained TiO(2) nanocrystals reacted with concentrate NaOH solution, yielding
      hollow titanate nanotubes. Consequently, there are reversible transformation
      pathways for transitions between the titanates and the titanium dioxide
      polymorphs, via wet-chemical reactions at moderate temperatures. The significance
      of these findings arises because such transitions can be engineered to produce
      numerous delicate nanostructures under moderate conditions. To demonstrate the
      commercial application potential of these processes, we also report titanate and
      TiO(2) nanostructures synthesized directly from rutile minerals and industrial
      grade rutiles by a new scheme of hydrometallurgical reactions.

PMID- 15869296
TI  - The remarkable axial lability of iron(III) corrole complexes.
AB  - Flash photolysis of nitrosyl tris(aryl)corrolate complexes of iron(III),
      Fe(Ar(3)C)(NO) (Ar(3)C(3-) = 5,10,15-tris(4-nitro-phenyl)corrolate (TNPC(3-)),
      5,10,15-tris(phenyl)corrolate (TPC(3-)) or 5,10,15-tris(4-tolyl)corrolate
      (H(3)TTC(3-))) leads to NO labilization. This is followed by the rapid reaction
      of NO with Fe(III)(C) to regenerate the starting complex. The second-order rate
      constants for the back reactions (k(NO)) were determined to be many orders of
      magnitude faster than the corresponding reactions of ferric porphyrin complexes
      and indeed are reminiscent of the very large values seen for those of the
      corresponding ferrous porphyrin analogues. These data are interpreted in terms of
      the strongly electron-donating character of the trianionic corrolate ligand and
      the likely triplet electronic configuration of the iron(III) complex. These
      reduce the affinity of the metal centers to Lewis bases to the extent that axial
      ligands bind very weakly or not at all. This property is illustrated by the
      nearly identical k(NO) values ( approximately 10(9) M(-1) s(-1) at 295 K)
      recorded for the back reaction of Fe(III)(TNPC) with NO after flash photolysis of
      Fe(TNPC)(NO) in toluene solution and in THF solution. Softer Lewis bases have a
      somewhat greater effect; for example, studies in 1:9 (v:v) acetonitrile:toluene
      and 1:9 pyridine:toluene gave k(NO) values decreased approximately 33% and
      approximately 85%, respectively, but these both remain >10(8) M(-1) s(-1). The
      potential roles of Lewis bases in controlling the dynamics of NO addition to
      Fe(TNPC) in toluene was investigated in greater detail by determining the rates
      as a function of pyridine concentration over a wide range (10(-4) to 2.5 M).
      These data suggest that, while a monopyridine complex, presumably Fe(TNPC)(py),
      is readily formed (K approximately 10(4) M), this species is about one-sixth as
      reactive as Fe(TNPC) itself. It appears that a much less reactive bis(pyridine)
      complex also is formed at high [py] but the equilibrium constant is quite small
      (<1 M(-1)).

PMID- 15869297
TI  - A hybrid quantum dot-antibody fragment fluorescence resonance energy transfer
      based TNT sensor.
AB  - We demonstrate the use of luminescent QDs conjugated to antibody fragments to
      develop solution-phase nanoscale sensing assemblies, based on fluorescence
      resonance energy transfer (FRET) for the specific detection of the explosive
      2,4,6-trinitrotoluene (TNT) in aqueous environments. The hybrid sensor consists
      of anti-TNT specific antibody fragments attached to a hydrophilic QD via metal
      affinity coordination. A dye-labeled TNT analogue prebound in the antibody
      binding site quenches the QD photoluminescence via proximity-induced FRET.
      Analysis of the data collected at increasing dye-labeled analogue to QD ratios
      provided an insight into understanding how the antibody fragments self-assemble
      on the QD. Addition of soluble TNT displaces the dye-labeled analogue,
      eliminating FRET and resulting in a concentration-dependent recovery of QD
      photoluminescence. Sensor performance and specificity were evaluated.

PMID- 15869298
TI  - Phospholipid morphologies on photochemically patterned silane monolayers.
AB  - We have studied the spreading of phospholipid vesicles on photochemically
      patterned n-octadecylsiloxane monolayers using epifluorescence and imaging
      ellipsometry measurements. Self-assembled monolayers of n-octadecylsiloxanes were
      patterned using short-wavelength ultraviolet radiation and a photomask to produce
      periodic arrays of patterned hydrophilic domains separated from hydrophobic
      surroundings. Exposing these patterned surfaces to a solution of small
      unilamellar vesicles of phospholipids and their mixtures resulted in a complex
      lipid layer morphology epitaxially reflecting the underlying pattern of
      hydrophilicity. The hydrophilic square regions of the photopatterned OTS
      monolayer reflected lipid bilayer formation, and the hydrophobic OTS residues
      supported lipid monolayers. We further observed the existence of a boundary
      region composed of a nonfluid lipid phase and a lipid-free moat at the interface
      between the lipid monolayer and bilayer morphologies spontaneously corralling the
      fluid bilayers. The outer-edge of the boundary region was found to be accessible
      for subsequent adsorption by proteins (e.g., streptavidin and BSA), but the inner
      edge closer to the bilayer remained resistant to adsorption by protein or
      vesicles. Mechanistic implications of our results in terms of the effects of
      substrate topochemical character are discussed. Furthermore, our results provide
      a basis for the construction of complex biomembrane models, which exhibit
      fluidity barriers and differentiate membrane properties based on correspondence
      between lipid leaflets. We also envisage the use of this construct where two
      dimensionally fluid, low-defect lipid layers serve as sacrificial resists for the
      deposition of protein and other material patterns.

PMID- 15869299
TI  - A charge-transfer-induced spin transition in a discrete complex: the role of
      extrinsic factors in stabilizing three electronic isomeric forms of a cyanide
      bridged co/fe cluster.
AB  - A series of bimetallic, trigonal bipyramidal clusters of type {[Co(N
      N)(2)](3)[Fe(CN)(6)](2)} are reported. The reaction of {Co(tmphen)(2)}(2+) with
      [Fe(CN)(6)](3)(-) in MeCN affords {[Co(tmphen)(2)](3)[Fe(CN)(6)](2)} (1). The
      cluster can exist in three different solid-state phases: a red crystalline phase,
      a blue solid phase obtained by exposure of the red crystals to moisture, and a
      red solid phase obtained by desolvation of the blue solid phase in vacuo. The
      properties of cluster 1 are extremely sensitive to both temperature and solvent
      content in each of these phases. Variable-temperature X-ray crystallography;
      (57)Fe Mossbauer, vibrational, and optical spectroscopies; and magnetochemical
      studies were used to study the three phases of 1 and related compounds,
      Na{[Co(tmphen)(2)](3)[Fe(CN)(6)](2)}(ClO(4))(2) (2),
      {[Co(bpy)(2)](3)[Fe(CN)(6)](2)}[Fe(CN)(6)](1/3) (3), and
      {[Ni(tmphen)(2)](3)[Fe(CN)(6)](2)} (4). The combined structural and spectroscopic
      investigation of 1-4 leads to the unambiguous conclusion that 1 can exist in
      different electronic isomeric forms, {Co(III)(2)Co(II)Fe(II)(2)} (1A),
      {Co(III)Co(II)(2)Fe(III)Fe(II)} (1B), and {Co(II)(3)Fe(III)(2)} (1C), and that it
      can undergo a charge-transfer-induced spin transition (CTIST). This is the first
      time that such a phenomenon has been observed for a Co/Fe molecule.

PMID- 15869300
TI  - Three-dimensional low symmetry mesoporous silica structures templated from tetra
      headgroup rigid bolaform quaternary ammonium surfactant.
AB  - Two kinds of highly ordered mesoporous silica materials (FDU-11, FDU-13) with
      novel three-dimensional (3-D) tetragonal and orthorhombic structures were
      synthesized by using tetra-headgroup rigid bolaform quaternary ammonium
      surfactant
      [(CH(3))(3)NCH(2)CH(2)CH(2)N(CH(3))(2)CH(2)(CH(2))(11)OC(6)H(4)C(6)H(4)O(CH(2))(1
      )CH(2)N(CH(3))(2)CH(2)CH(2)CH(2)N(CH(3))(3).4Br] (C(3-12-12)(-)(3)) as a template
      under alkaline conditions. High-resolution transmission electron microscopy
      (HRTEM), small-angle X-ray scattering (SAXS), and X-ray diffraction (XRD) show
      that mesoporous silica FDU-11 has primitive tetragonal P4/mmm structure with cell
      parameters a = b = 8.46 nm, c = 5.22 nm, and c/a ratio = 0.617. N(2) sorption
      isotherms show that calcined FDU-11 has a high BET surface area of approximately
      1490 m(2)/g, a uniform pore size of approximately 2.72 nm, and a pore volume of
      approximately 1.88 cm(3)/g. Mesoporous silica FDU-13 has primitive orthorhombic
      Pmmm structure. The cell parameters are a = 9.81, b = 5.67, and c = 3.66 nm. N(2)
      sorption isotherms show that calcined FDU-13 has a high BET surface area of 1210
      m(2)/g, a uniform mesopore size of approximately 1.76 nm, and a large pore volume
      of approximately 1.83 cm(3)/g. Such low symmetries for 3-D mesostructures
      (tetragonal and orthorhombic system) have not been observed before even in
      amphiphilic liquid crystals, which maybe resulted from an oblate aggregation of
      the bolaform surfactant and its strong electrostatic interaction with inorganic
      precursor. A probable mechanism has been proposed for the formation of such a 3-D
      low symmetrical mesostructure. These results will further extend the synthesis of
      mesoporous materials and may open up new opportunities for their new applications
      in catalysis, separation, and nanoscience.

PMID- 15869301
TI  - Efficient preparation of functionalized hybrid organic/inorganic Wells-Dawson
      type polyoxotungstates.
AB  - Hybrid organic/inorganic Wells-Dawson polyoxotungstates have been prepared
      through addition of functionalized tricholorostannanes to lacunary alpha(2)- and
      alpha(1)-[P(2)W(17)O(61)](10-). Coupling of amines and alcohols to
      polyoxotungstate platforms led to new structures in good yields. Coupling of
      chiral amines to the previously unknown organotin-substituted alpha(1)
      derivatives allowed the isolation of diastereomers, which feature in some cases
      split (1)H, (13)C, and (31)P NMR spectra. This is the first example of NMR
      observation of a single pair of diastereomers in the alpha(1)-Wells-Dawson
      series. It opens the way to potential resolution of those chiral
      polyoxotungstates.

PMID- 15869302
TI  - 57Fe-labeled octamethylferrocenium tetrafluoroborate. X-ray crystal structures of
      conformational isomers, hyperfine interactions, and spin-lattice relaxation by
      Moessbauer spectroscopy.
AB  - X-ray structure determinations of two different single crystals of
      octamethylferrocenium tetrafluoroborate (OMFc(+)BF(4)(-)) revealed conformational
      polymorphism with ligand twist angles of 180 degrees and 108 degrees ,
      respectively. Their concomitant occurrence could be explained by the small
      lattice energy difference of 3.2 kJ mol(-1). Temperature-dependent Moessbauer
      spectroscopy of (57)Fe-labeled OMFc(+)BF(4)(-) over the range 90 < T < 370 K did
      not show the anomalous sudden increase in the motion of the metal atom as
      observed in neutral OMFc. Broadened absorption curves characteristic of
      relaxation spectra were obtained with an isomer shift of 0.466(6) mm s(-1) at 90
      K. The temperature dependence of the isomer shift corresponded to an effective
      vibrating mass of 79 +/- 10 Da and, in conjunction with the temperature
      dependence of the recoil-free fraction, to a Moessbauer lattice temperature of 89
      K. The spin relaxation rate could be better described by an Orbach rather than a
      Raman process. At 400 K, a reversible solid-solid transition to a plastic
      crystalline mesophase was noted.

PMID- 15869303
TI  - Electric field induced switching behaviors of monolayer-modified silicon
      surfaces: surface designs and molecular dynamics simulations.
AB  - Electric field induced switching behaviors of a series of low-density omega
      carboxyalkyl modified H-Si(111) and the mixed omega-carboxyalkyl/alkyl covered H
      Si(111) have been simulated by using molecular dynamics (MD) simulation
      techniques. The external electric fields may drive surface-confined molecules to
      reversibly change conformations between the all-trans (switching "on") and the
      mixed trans-gauche (switching "off") states. Such surfaces switch wettabilities
      between the hydrophilic state and the moderately hydrophobic state. It has been
      found in broad ranges of intensities of applied electric fields, -2.0 x 10(9) V/m
      < or = E(down) < or = 0 and 1.8 x 10(9) V/m < or = E(up) < or = 7.3 x 10(9) V/m,
      both the low-density (11.1%-33.3%) omega-carboxyalkyl and the mixed omega
      carboxyalkyl/alkyl (in mole fraction of 0.4 < or = N(carboxyalkyl) : N(alkyl) <
      or = 3.0) monolayers covering H-Si(111) exhibit conformational switching in the
      aqueous medium. The critical intensity of the electric field, E(up) = 1.8 x 10(9)
      V/m, which is required to trigger the switches is observed by our MD simulations
      and further rationalized by a thermodynamical model. Some important factors in
      the control of switching performances, such as the steric hindrances, the
      formation of the electric double layer at the monolayer/electrolyte solution
      interface, the hydration effects of carboxylate anions, the components of
      surrounding electrolyte solutions, as well as the rigidity of surface-confined
      chains are elucidated. The lower ionic strength and additions of acetonitrile
      molecules in the surrounding aqueous solution can reduce the value of critical
      intensity of the electric field and hence facilitate the realization of
      switching. Some practical considerations in construction and optimum design of
      switching surfaces are also suggested.

PMID- 15869304
TI  - Ultra-sensitive imaging and interfacial analysis of patterned hydrophilic SAM
      surfaces using energy dissipation chemical force microscopy.
AB  - Energy dissipation chemical force microscopy has been used to analyze the
      dissipative properties of chemically similar regions of hydroxyl- and carboxyl
      terminated SAMs on gold with a hydroxyl-terminated tip. Energy dissipation
      imaging quantitatively isolates dissipative interfacial interactions from
      topography, producing a significantly more informative image than phase imaging.
      Also, energy dissipation force curves probed the rheological properties of the
      tip-sample interaction. Viscosity of the confined water increased slightly over
      that of the bulk, and SAM deformation was found to have a longer retardation time
      than restructuring of interfacial ions and solvent during tip-sample contact.

PMID- 15869305
TI  - The effect of the particle size on the kinetics of CO electrooxidation on high
      surface area Pt catalysts.
AB  - Using high-resolution transmission electron microscopy (TEM), infrared reflection
      absorption spectroscopy (IRAS), and electrochemical (EC) measurements, platinum
      nanoparticles ranging in size from 1 to 30 nm are characterized and their
      catalytic activity for CO electrooxidation is evaluated. TEM analysis reveals
      that Pt crystallites are not perfect cubooctahedrons, and that large particles
      have "rougher" surfaces than small particles, which have some fairly smooth (111)
      facets. The importance of "defect" sites for the catalytic properties of
      nanoparticles is probed in IRAS experiments by monitoring how the vibrational
      frequencies of atop CO (nu(CO)) as well as the concomitant development of
      dissolved CO(2) are affected by the number of defects on the Pt nanoparticles. It
      is found that defects play a significant role in CO "clustering"on nanoparticles,
      causing CO to decrease/increase in local coverage, which yields to anomalous
      redshift/blueshift nu(CO) frequency deviations from the normal Stark-tuning
      behavior. The observed deviations are accompanied by CO(2) production, which
      increases by increasing the number of defects on the nanoparticles, that is, 1 <
      or = 2 < 5 << 30 nm. We suggest that the catalytic activity for CO adlayer
      oxidation is predominantly influenced by the ability of the surface to dissociate
      water and to form OH(ad) on defect sites rather than by CO energetics. These
      results are complemented by chronoamperometric and rotating disk electrode (RDE)
      data. In contrast to CO stripping experiments, we found that in the backsweep of
      CO bulk oxidation, the activity increases with decreasing particle size, that is,
      with increasing oxophilicity of the particles.

PMID- 15869306
TI  - Water at a hydrophilic solid surface probed by ab initio molecular dynamics:
      inhomogeneous thin layers of dense fluid.
AB  - We present a microscopic model of the interface between liquid water and a
      hydrophilic, solid surface, as obtained from ab initio molecular dynamics
      simulations. In particular, we focused on the (100) surface of cubic SiC, a
      leading semiconductor candidate for biocompatible devices. Our results show that
      in the liquid in contact with the clean substrate, molecular dissociation occurs
      in a manner unexpectedly similar to that observed in the gas phase. After full
      hydroxylation takes place, the formation of a thin (approximately 3 A)
      interfacial layer is observed, which has higher density than bulk water and forms
      stable hydrogen bonds with the substrate. The presence of this thin layer points
      at rather weak effects on the structural properties of water induced by a one
      dimensional confinement between approximately 1.3 nm hydrophilic substrates. In
      addition, our results show that the liquid does not uniformly wet the surface,
      but molecules preferably bind along directions parallel to the Si dimer rows.

PMID- 15869307
TI  - Electrostatic recognition and induced fit in the kappa-PVIIA toxin binding to
      Shaker potassium channel.
AB  - Brownian dynamics (BD) and molecular dynamics (MD) simulations and electrostatic
      calculations were performed to study the binding process of kappa-PVIIA to the
      Shaker potassium channel and the structure of the resulting complex. BD
      simulations, guided by electrostatic interactions, led to an initial alignment
      between the toxin and the channel protein. MD simulations were then carried out
      to allow for rearrangements from this initial structure. After approximately 4
      ns, a critical "induced fit" process was observed to last for approximately 2 ns.
      In this process, the interface was reorganized, and side chains were moved so
      that favorable atomic contacts were formed or strengthened, while unfavorable
      contacts were eliminated. The final complex structure was stabilized through
      electrostatic interactions with the positively charged side chain of Lys7 of
      kappa-PVIIA deeply inserted into the channel pore and other hydrogen bonds and by
      hydrophobic interactions involving Phe9 and Phe23 of the toxin. The validity of
      the predicted structure for the complex was assessed by calculating the effects
      of mutating charged and polar residues of both the toxin and the channel protein,
      with the calculated effects correlating reasonably well with experimental data.
      The present study suggests a general binding mechanism, whereby proteins are pre
      aligned in their diffusional encounter by long-range electrostatic attraction,
      and nanosecond-scale rearrangements within the initial complex then lead to a
      specifically bound complex.

PMID- 15869308
TI  - Charge separation and efficient light energy conversion in sensitized mesoscopic
      solar cells based on binary ionic liquids.
AB  - A 7.4% power conversion efficiency at air mass (AM) 1.5 full sunlight was reached
      with a mesoscopic solar cell employing a new binary ionic liquid electrolyte
      composed of 1-propyl-3-methylimidazolium iodide and 1-ethyl-3-methylimidazolium
      tricyanomethanide in conjunction with the amphiphilic ruthenium complex NaRu(4
      carboxylic acid-4'-carboxylate)(4,4'-dinonyl-2,2'-bipyridine)(NCS)(2), coded as Z
      907Na. Ultramicroelectrode voltammetric, nanosecond laser transient absorbance,
      and photovoltaic measurements show that a high iodide concentration is required
      for dye regeneration to compete efficiently with charge recombination. A
      surprisingly fast reductive quenching process is turned on in pure iodide melts.
      This channel is unproductive, explaining the lower photocurrents observed under
      these conditions.

PMID- 15869309
TI  - Ultrafast dynamics of 2E state formation in Cr(acac)3.
AB  - Femtosecond time-resolved absorption spectroscopy has been used to elucidate the
      excited-state dynamics associated with formation of the (2)E excited state in a
      Cr(III) transition metal complex. Cr(acac)(3) (where acac is the deprotonated
      monoanion of acetylacetone) exhibits monophasic decay kinetics with tau = 1.1 +/-
      0.1 ps following excitation into the lowest-energy ligand-field absorption band;
      the time constant is found to be independent of both excitation and probe
      wavelength across the entire (4)A(2) --> (4)T(2) absorption envelope. The lack of
      a significant shift in the excited-state absorption spectrum combined with the
      observed spectral narrowing is consistent with an assignment of this process as
      vibrational cooling (k(vib)) in the (2)E state. The data on Cr(acac)(3) indicate
      that intersystem crossing associated with the (4)T(2) --> (2)E conversion occurs
      at a rate k(ISC) > 10(13) s(-)(1) and furthermore competes effectively with
      vibrational relaxation in the initially formed (4)T(2) state. Excitation into the
      higher energy (4)LMCT state (lambda(ex) = 336 nm) gives rise to biphasic kinetics
      with tau( 1) = 50 +/- 20 fs and tau( 2) = 1.2 +/- 0.2 ps. The slower component is
      again assigned to vibrational cooling in the (2)E state, whereas the
      subpicosecond process is attributed to conversion from the charge-transfer to the
      ligand-field manifold. In addition to detailing a process central to the
      photophysics of Cr(III), these results reinforce the notion that the conventional
      picture of excited-state dynamics in which k(vib) > k(IC) > k(ISC) does not
      generally apply when describing excited-state formation in transition metal
      complexes.

PMID- 15869310
TI  - Free energy landscape of A-DNA to B-DNA conversion in aqueous solution.
AB  - The interconversion between the well-characterized A- and B-forms of DNA is a
      structural transition for which the intermediate states and the free energy
      difference between the two endpoints are not known precisely. In the present
      study, the difference between the Root Mean Square Distance (RMSD) from canonical
      A-form and B-form DNA is used as an order parameter to characterize this free
      energy difference using umbrella sampling molecular dynamics (MD) simulations
      with explicit solvent. The constraint imposed along this order parameter allows
      relatively unrestricted evolution of the intermediate structures away from both
      canonical A- and B-forms. The free energy difference between the A- and B-forms
      for the hexamer DNA sequence CTCGAG in aqueous solution is conservatively
      estimated to be at least 2.8 kcal/mol. A continuum of intermediate structures
      with no well-defined local minima links the two forms. The absence of any major
      barriers in the free energy surface is consistent with spontaneous conversion of
      the A-form DNA to B-form DNA in unconstrained simulations. The extensive sampling
      in the MD simulations (>0.1 mus) also allowed quantitative energetic
      characterization of local backbone conformational variables such as sugar
      pseudorotation angles and BI/BII state equilibria and their dependence on base
      identity. The absolute minimum in the calculated free energy profile corresponds
      closely to the crystal structure of the hexamer sequence, indicating that the
      present method has the potential to identify the most stable state for an
      arbitrary DNA sequence in water.

PMID- 15869311
TI  - A readily available chiral Ag-based N-heterocyclic carbene complex for use in
      efficient and highly enantioselective Ru-catalyzed olefin metathesis and Cu
      catalyzed allylic alkylation reactions.
AB  - A new chiral bidentate N-heterocyclic carbene (NHC) ligand has been designed and
      synthesized. The NHC ligand bears a chiral diamine backbone and an achiral
      biphenol group; upon metal complexation (derived from Ag(I), Ru(II), or Cu(II)),
      the diamine moiety induces >98% diastereoselectivity such that the biaryl unit
      coordinates to the metal center to afford the desired complex as a single
      atropisomer. Because the ligand does not require optically pure biaryl amino
      alcohols, its synthesis is significantly shorter and simpler than the related
      first generation ligands bearing a chiral binaphthyl-based amino alcohol. The
      chiral NHC ligand can be used in the preparation of highly effective Ru- and Cu
      based complexes (prepared and used in situ from the Ag(I) carbene) that promote
      enantioselective olefin metathesis and allylic alkylations with scope that is
      improved from previously reported protocols. In many cases, transformations
      promoted by the chiral NHC-based complexes proceed with higher enantioselectivity
      and reactivity than was observed with previously reported complexes.

PMID- 15869312
TI  - Photochemistry of an azido-functionalized cryptand: controlling the reactivity of
      an extremely long-lived singlet aryl nitrene by complexation to alkali cations.
AB  - Photolysis of the cryptand 1, bearing an intraannular azido substituent, results
      in a complex photochemistry. Low-temperature photolysis yields the triplet
      nitrene (3)2, which has been characterized by EPR spectroscopy. Small differences
      in ZFS parameters are detected between the uncomplexed nitrene-functionalized
      ligand (in EtOH: D' = 0.93 cm(-1)) and its sodium (NaBr@(3)2 in EtOH: D' = 0.88
      cm(-1)) and potassium (KBr@(3)2 in MTHF: D' = 0.89 cm(-1)) complexes. If the
      photolysis of the free ligand is conducted at ambient temperature, a derivative
      of o-aminobenzaldehyde 4 is found to be the main product, which is formed by
      reaction of the o-iminoquinone methide 9 with water. The latter can be detected
      by UV/vis spectroscopy. Its lifetime is tau = 254 s in acetonitrile solution at
      ambient temperature. In the presence of diethylamine, the methyleneazepine
      derivative 5 is formed, which is indicative of didehydroazepine formation (7).
      Room-temperature photolysis of acetonitrile solutions of the sodium or potassium
      complexes also results in formation of the o-aminobenzaldehyde derivative. In the
      presence of diethylamine, however, no methyleneazepine 5 is found. Formation of
      the aniline derivative 8 instead points to free radical processes. Laser flash
      photolysis (LFP) of acetonitrile solutions of 1 leads to the detection of a short
      lived (tau = 1.4 mus, lambda(max) = 445 nm plus weak absorption at lambda > 500
      nm) intermediate A, which decays to transient B (tau = 8 ms, lambda(max) = 295
      and ca. 350-400 nm). LFP of acetonitrile solutions of complexes NaBr@1 and KBr@1
      gives similar transient spectra. In the presence of sodium and potassium cations,
      the lifetime of the short-lived transient A is reduced (Na(+): A', tau = 200 ns;
      K(+): A", tau = 160 ns). Transients A' and A" decay to long-lived transients B' +
      C' (B" + C"). Based on the results of our product studies, a comparison with the
      low-temperature results, and quantum mechanical calculations, the transients A,
      A', and A" are identified as singlet nitrenes (1)2, NaBr@(1)2, and KBr@(1)2,
      while the long-lived transients B, B', and B" are assigned to didehydroazepines
      7, NaBr@7, and KBr@7. Transients C' and C" can be assigned to aminyl radicals
      NaBr@16 and KBr@16.

PMID- 15869313
TI  - A suite of 2H NMR spin relaxation experiments for the measurement of RNA
      dynamics.
AB  - A suite of (2)H-based spin relaxation NMR experiments is presented for the
      measurement of molecular dynamics in a site-specific manner in uniformly (13)C,
      randomly fractionally deuterated ( approximately 50%) RNA molecules. The
      experiments quantify (2)H R(1) and R(2) relaxation rates that can subsequently be
      analyzed to obtain information about dynamics on a pico- to nanosecond time
      scale. Sensitivity permitting, the consistency of the data can be evaluated by
      measuring all five rates that are accessible for a spin 1 particle and
      establishing that the rates obey relations that are predicted from theory. The
      utility of the methodology is demonstrated with studies of the dynamics of a 14
      mer RNA containing the UUCG tetraloop at temperatures of 25 and 5 degrees C. The
      high quality of the data, even at 5 degrees C, suggests that the experiments will
      be of use for the study of RNA molecules that are as large as 30 nucleotides.

PMID- 15869314
TI  - Theoretical study of the suicide inhibition mechanism of the enzyme pyruvate
      formate lyase by methacrylate.
AB  - The determination of pyruvate formate lyase crystallographic structure brought
      new insights to its mechanism of reaction and presented the possibility of a
      direct attack to the substrate from cysteine 418 as opposed to the previously
      expected cysteine 419. An inhibition study performed by Knappe and co-workers,
      using substrate-analogue methacrylate, confirms that cysteine 418 is most likely
      to add directly to pyruvate, since an inhibition product has been found as a
      substituent in this residue. The work presented here consists of a study of the
      inhibition mechanism of pyruvate formate lyase by methacrylate, using density
      functional theory with the hybrid B3LYP functional. We were able to determine all
      pertinent structures, confirm the proposed experimental mechanism, and add
      important detail to the energy profile associated with the mechanism of
      inhibition. Additionally, the obtained results provide the energy values for both
      the chemical reaction and the stereochemical reorganization necessary in order
      for the thiol-methacrylate adduct to come within reactional reach of Cys419.

PMID- 15869316
TI  - Pharmacokinetic profile and clinical efficacy of long-acting risperidone:
      potential benefits of combining an atypical antipsychotic and a new delivery
      system.
AB  - Continuous long-term antipsychotic therapy is required for patients with
      schizophrenia to optimise treatment benefits. The use of long-acting
      antipsychotic preparations can help to ensure compliance with therapy and has
      been shown to improve efficacy in relapse prevention when compared with oral
      agents. How- ever, the use of long-acting agents has been limited, since this
      approach to patient care has only been available with conventional drugs. The
      atypical antipsychotic agents have provided a new option for the treatment of
      schizophrenia. However, entwined with health system limitations, partial or non
      compliance remains a problem with oral atypical antipsychotic agents. Combining
      the attributes of the atypical antipsychotic class with the pharmacokinetic
      profile and compliance advantages of a long-acting formulation could potentially
      be an important advance in the management of patients requiring continuous anti-
      psychotic therapy. This review considers the available clinical data supporting
      possible advantages for the only long-acting atypical agent currently available,
      long-acting risperidone, as a microsphere formulation. The drug-delivery
      technology employed provides a sustained therapeutic plasma level, with
      administration once every 2 weeks, and this is translated into improved symptom
      control and improved quality of life, even in patients already deemed clinically
      stable on an oral agent or on a conventional depot antipsychotic.

PMID- 15869317
TI  - Distribution of zolmitriptan into the CNS in healthy volunteers: a positron
      emission tomography study.
AB  - OBJECTIVE: Triptans are highly effective in the treatment of migraine. Both
      central and peripheral mechanisms of action have been suggested. Until now, firm
      data about the passage of triptans into the CNS in humans have been lacking. The
      aim of the current study was to evaluate, using positron emission tomography
      (PET), the uptake and distribution of zolmitriptan into the CNS after intranasal
      administration. SUBJECTS AND METHODS: Eight healthy volunteers, five males and
      three females (mean ages 23 and 26 years, respectively), were included.
      Radioactive [carbonyl-11C]zolmitriptan was infused intravenously for 5 minutes on
      two occasions: once alone, and once 30-40 minutes after intranasal administration
      of unlabelled zolmitriptan 5 mg. PET was used to measure the concentration of
      labelled zolmitriptan in the brain, from the start of the tracer infusion for 90
      minutes. Regional cerebral blood volume was determined with [15O]carbon monoxide.
      In addition, an MRI scan was performed to obtain anatomical information. The PET
      images were analysed quantitatively for different areas of the brain, generating
      [11C]zolmitriptan time-activity data corrected for circulating tracer activity.
      The rate of uptake of intranasal zolmitriptan into the CNS was estimated by
      kinetic modelling using the PET data. RESULTS: PET data from this study
      demonstrate a rapid dose-proportional uptake of [11C]zolmitriptan into the brain.
      Significant concentrations of [11C]zolmitriptan were found in all brain regions
      studied. Calculated CNS concentrations after intranasal zolmitriptan
      administration showed a gradual increase, reaching about 2 nM (0.5 microg/L) 30
      minutes after administration and 3.5 nM (1.0 microg/L), or one-fifth of the
      plasma concentration, 1 hour after administration. Five minutes after
      zolmitriptan administration, the mean CNS concentration had already reached 0.5
      nM, which is higher than in vitro values for initiation of the agonistic action
      on 5-HT(1B/1D) receptors. CONCLUSION: This study demonstrates by direct
      measurements that zolmitriptan enters the brain parenchyma in humans, achieving
      an uptake rate and concentration compatible with a central mode of action.

PMID- 15869318
TI  - Economic and epidemiological modelling of full-length antihaemophilic factor
      (recombinant), plasma/albumin-free method, in previously treated patients with
      haemophilia A : comparison with B-domain deleted rFVIII, and value of potential
      viral transmission reduction due to plasma/albumin-free status.
AB  - OBJECTIVES: To the extent that current recombinant clotting factor concentrates
      contain even trace amounts of human or animal protein, there is continuing
      potential for transmission of nonenveloped viruses, including hepatitis A, and
      parvovirus, and the theoretical potential for transmission of relatively unknown
      agents, such as prions (Creutzfeldt-Jakob disease, or its variant). Full-length
      antihaemophilic factor (recombinant), plasma/albumin-free method (rAHF-PFM;
      Advate), represents a novel pharmacotherapeutic option for the management of
      haemophilia A. This investigation was designed to discern: (i) the efficacy-based
      use pattern (International Units [IUs]) of rAHF-PFM versus B-domain deleted
      rFVIII (BDDrFVIII; ReFacto) required to resolve a bleeding episode (event) among
      previously treated patients with haemophilia A employing on-demand treatment;
      (ii) the health service expenditure pattern (percentage differential; payor's
      perspective) associated with use of rAHF-PFM versus BDDrFVIII among previously
      treated patients with haemophilia A employing on-demand treatment; and (iii) the
      fiscal utility attributable to the plasma/albumin-free status of rAHF-PFM under
      the assumed emergence of a novel and infectious blood (plasma)-borne virus.
      MATERIALS AND METHODS: Data stemming from phase II/phase III clinical trials of
      rAHF-PFM, together with published literature on BDDrFVIII, afforded calculation
      of the probability of occurrence for specific endpoints of interest (e.g. non
      response to first infusion). Monte Carlo simulation, a decision-analytical
      framework parameterised with stochastic (random) and deterministic (fixed)
      components (10 000 iterations per month [or year] of age examined [3, 6, 9
      months; years 1 through 19; and years 20, 30, 40, 50, 60, 70 and 80]) was used to
      compare: (i) the efficacy-based use pattern by treatment option; and (ii) the
      health service utilisation-based expenditure pattern by treatment option,
      accounting for the need for subsequent infusion(s), and potential complications
      (use of services) stemming from failure of the initial infusion (five scenarios).
      Theoretical and direct modelling methods for assessing the fiscal utility
      attributable to the plasma/albumin-free status of rAHF-PFM under the assumed
      emergence of a novel and infectious blood (plasma)-borne virus were developed.
      Assumptions included: (i) a low population infection rate (<5%); (ii) annual
      health service expenditures equivalent to 5% of that observed with HIV/AIDS; and
      (iii) the number of bleeding events experienced per year were 6, 9 or 12.
      RESULTS: Monte Carlo simulation-replicated simulations per year of age examined
      revealed: (i) use of rAHF-PFM resulted in a 12.20% median reduction in the number
      of IUs required to resolve a bleeding episode (event) relative to BDDrFVIII (p <
      0.05); and (ii) a health service utilisation-based savings [primary care;
      hospital] (p < 0.05; range 13.74-39.34% [dependent on intensity (sequencing) of
      care required]) with rAHF-PFM relative to BDDrFVIII. The overall scenario
      weighted health service utilisation-based savings was 16.94% (p < 0.05). Under
      the assumption of the emergence of a novel and infectious blood (plasma)-borne
      virus, deterministic models for persons weighing 20 kg, 50 kg and 80 kg all
      revealed a savings potential ($US per IU) with use of rAHF-PFM relative to use of
      a non-plasma/albumin-free product. CONCLUSION: Use of rAHF-PFM in on-demand
      management of haemophilia A offers enhanced patient safety and represents a
      fiscally prudent therapeutic strategy.

PMID- 15869319
TI  - Effects of antioxidant vitamins on glutathione depletion and lipid peroxidation
      induced by restraint stress in the rat liver.
AB  - BACKGROUND AND AIM: Stress as a cofactor has been reported to affect the
      progression and severity of several diseases. The influence of stress on the
      liver is of interest from the clinical point of view because stress plays a
      potential role in aggravating liver diseases in general and hepatic inflammation
      in particular, probably through generation of reactive oxygen species. The
      present study was undertaken to investigate the potential of the antioxidant
      vitamins A (retinol), E (tocopherol) and C (ascorbic acid) individually and in
      combination (vitamin E + C) to modulate restraint stress-induced oxidative
      changes. These effects were determined by measuring changes in hepatic levels of
      free radical scavenging enzymes such as superoxide dismutase (SOD), glutathione-S
      transferase (GST) and catalase, as well as levels of total glutathione (GSH),
      malondialdehyde (MDA), aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT). METHODS: Immobilisation was achieved by placing the
      animals in wire mesh cages of their size. The rats were orally administered
      vitamins A, E and C individually and in combination (E + C) prior to and after 6
      hours of immobilisation stress exposure. The hepatic levels of SOD, GST,
      catalase, GSH and MDA were determined by spectrophotometric methods. Liver SOD
      activity was assayed by monitoring the amount of enzyme required to inhibit
      autoxidation of pyrogallol by 50%. Hepatic GST was monitored by following the
      increase in absorbance at 340 nm of CDNB-GSH conjugate generated due to GST
      catalysis between GSH and CDNB. Catalase activity in liver tissues was determined
      using peroxidase as the substrate. Lipid peroxidation was measured by determining
      the level of thiobarbituric acid reactive substances. ALT and AST were determined
      by commercial kits. RESULTS: Six hours of immobilisation stress caused a decrease
      in liver levels of SOD (p = 0.001), catalase (p = 0.031), GST (p = 0.021) and GSH
      (0.013), while levels of MDA (p = 0.0015), AST (p = 0.05) and ALT (p = 0.046)
      were increased compared with non-stressed control rats. Both pre-vitamin stress
      and post-vitamin stress treatments either alone or in combination were associated
      with increased normalisation of these parameters towards control values, with
      post-vitamin treatment being the more effective of the two. Vitamins E and C
      individually were found to be more effective in restoring the endogenous
      antioxidant system than vitamin A. The combined vitamin (E + C) post-stress
      treatment was found to be effective but not additive in combating hepatic
      oxidative stress. The beneficial effects of these vitamin treatments were also
      reflected in reversions of altered AST and ALT levels towards their control
      values. CONCLUSION: Vitamins E or C alone or in combination can be given as
      prophylactic/therapeutic supplements for combating scavenging free radicals
      generated in liver tissue. This approach may reduce oxidative stress caused by
      diseases such as cirrhosis.

PMID- 15869320
TI  - Cilansetron: KC 9946.
AB  - Cilansetron [KC 9946] is a serotonin-3 receptor (5-HT(3)) antagonist under
      development with Solvay Pharmaceuticals for the treatment of irritable bowel
      syndrome with diarrhoea predominance (IBS-D), in both men and women.5-HT(3)
      antagonists inhibit the 5-HT(3) receptors, resulting in decreased GI motility,
      secretion and sensation, thereby improving symptoms of IBS-D. Current 5-HT(3)
      therapy indicated for IBS-D is approved for women only.IBS is one of the most
      common functional gastrointestinal disorders, affecting an estimated 10-20% of
      the population in developed countries. Approximately twice as many women as men
      are diagnosed with IBS; however, this discrepancy may be due to more women
      seeking medical care. IBS is a chronic and bothersome disorder, and its symptoms,
      although not life-threatening, have a negative impact on quality of life (QOL),
      interfering with social activities, relationships and work. The degree to which
      IBS reduces quality of life appears to be directly related to symptom severity
      and intensity. In July 2001, Solvay signed an agreement with Quintiles (CRO) in
      order to optimise clinical research for cilansetron. In April 2004, Solvay
      Pharmaceuticals submitted a new drug application (NDA) for cilansetron in the UK
      (for the European Union) for the treatment of irritable bowel syndrome with
      diarrhoea predominance, in both men and women. In April 2005, Solvay
      Pharmaceuticals received a 'not-approvable' action letter from the US FDA on its
      NDA for cilansetron for the treatment of irritable bowel syndrome with diarrhoea
      predominance (IBS-D), in both men and women. The letter requested additional
      clinical trials, and Solvay is currently examining its options and will discuss
      future steps with the FDA. Solvay submitted the NDA for cilansetron in the US in
      June 2004 and included an extensive Appropriate Use Plan as part of its
      submission. The NDA submission was based on efficacy and safety studies in around
      4000 patients worldwide with IBS-D. The FDA accepted for filing and granted
      priority review status for this NDA application in September 2004. According to
      Solvay's first half 2004 results, cilansetron is due to begin phase II clinical
      trials in Japan for the treatment of irritable bowel syndrome with diarrhoea
      predominance.

PMID- 15869321
TI  - Dextromethorphan/quinidine: AVP 923, dextromethorphan/cytochrome P450-2D6
      inhibitor, quinidine/dextromethorphan.
AB  - Avanir Pharmaceuticals in the US is developing a fixed-dose combination of
      dextromethorphan (30 mg), a weak NMDA antagonist/sigma 1 agonist, and quinidine
      (30 mg), a cytochrome P450-2D6 (CYP2D6) enzyme inhibitor [AVP 923, Neurodextrade
      mark]. Quinidine sustains therapeutic levels of dextromethorphan over a 12-hour
      dosing schedule by inhibiting oxidative first-pass metabolism of the drug, and is
      used in the combination product at 2.5-5.0% of its normal daily therapeutic dose.
      A rolling NDA for the treatment of emotional lability has been initiated, and
      phase II trials with dextromethorphan/quinidine for the treatment of neuropathic
      pain have been completed. Avanir is exploring partnering opportunities for
      dextromethorphan/quinidine in Europe and Japan. Prospective partners would carry
      out development and commercialisation in the licensed territory. Additionally, a
      co-promotion partner for the US is sought. Avanir Pharmaceuticals sublicensed
      this formulation of dextromethorphan from IriSys Research and Development. Avanir
      has exclusive rights to develop, manufacture and market
      dextromethorphan/quinidine for four potential indications: emotional lability,
      neuropathic pain, chronic cough and weaning drug-dependent patients from
      narcotics and antidepressants. Avanir will make milestone payments to Irisys upon
      US FDA acceptance of filing, marketing approval, and royalties based on product
      sales. Medison Pharma (Israel) has obtained development, marketing and
      distribution rights to the dextromethorphan/quinidine combination for the
      treatment of emotional lability in patients with multiple sclerosis in Israel.
      Avanir will fund all clinical development of the dextromethorphan/quinidine
      combination for the treatment of emotional lability. The phase II clinical trials
      with dextromethorphan/quinidine for the treatment of neuropathic pain have been
      completed. Results indicated that the combination significantly improved pain
      scores in patients with diabetic neuropathy. Phase III trials in this indication
      are expected to begin in 2005. Avanir has been issued with six patents in the US
      regarding dextromethorphan/quinidine and has a total of 14 pending applications,
      12 of which are in Europe.

PMID- 15869322
TI  - Efaproxiral: GSJ 61, JP 4, KDD 86, RS 4, RSR 13.
AB  - Efaproxiral [RSR 13, GSJ 61, JP 4, KDD 86, RS 4] is a synthetic, small-molecule,
      radiation-sensitising agent being developed by Allos Therapeutics primarily for
      the treatment of cancer. It works by binding and allosterically stabilising
      deoxyhaemoglobin in hypoxic regions of tumour tissue. This increases oxygen
      uptake of the tumour tissue and restores its sensitivity to radiation therapy,
      making therapy potentially more successful. This first-of-its-class compound is
      particularly applicable for the treatment of certain tumour types that lack
      oxygen, such as brain metastases. In contrast to conventional chemotherapeutic
      agents or radiation sensitisers, there is no requirement for efaproxiral to be
      administered directly into tumours or to cross the blood-brain barrier for it to
      display efficacy. Efaproxiral is under review for approval in the US and EU as an
      adjunct to whole-brain radiation therapy (WBRT) for the treatment of brain
      metastases originating from breast cancer. It is also under clinical evaluation
      for a variety of other cancers, including glioblastoma, non-small cell lung
      cancer (NSCLC) and cervical cancer. Allos is seeking partnership opportunities
      for efaproxiral's development and marketing. The company has indicated that the
      development of efaproxiral would be in cooperation with a corporate partner,
      according to its 2003 Annual Report. In 1994, Allos Therapeutics acquired
      exclusive worldwide rights to intellectual property relating to efaproxiral from
      the Center for Innovative Technology (CIT). Allos has entered into arrangements
      with two contract manufacturers for the supply of efaproxiral, and a third
      manufacturer for the supply of the formulated drug product. Hovione FarmaCiencia
      is the primary supplier of efaproxiral, and is contracted to manufacture
      sufficient quantities on a commercial scale. In addition, a second manufacturer,
      Raylo Chemicals, is also producing quantities of efaproxiral. In December 2003,
      Allos entered into a long-term development and supply agreement with Baxter
      Healthcare who will formulate the efaproxiral into an injection. Allos is also
      seeking to establish an alternate supplier of efaproxiral injection. Allos
      submitted a rolling NDA to the US FDA consisting of three data components.
      Submission began in the third quarter of 2003 and was completed by the fourth
      quarter of 2003. The first part of the application containing non-clinical
      information was submitted on 5 August 2003. The second part of the NDA containing
      information about efaproxiral's chemistry, manufacture and controls (CMC) was
      submitted in October 2003. Allos submitted its final component of the rolling NDA
      in December 2003. In February 2004, Allos announced that the FDA had accepted the
      company's NDA under priority review status. The FDA granted efaproxiral orphan
      drug status in August 2004 as an adjunct to WBRT for the treatment of brain
      metastases among breast cancer patients. Efaproxiral also received fast-track
      status in November 2000 for the same indication in the US. In February 2004,
      Allos initiated a phase III trial, called ENRICH (Enhancing Whole Brain Radiation
      Therapy In Patients with Breast Cancer and Hypoxic Brain Metastases) to
      investigate efaproxiral as an adjunct to WBRT for the treatment of brain
      metastases. Median survival time is the primary endpoint of the study. The
      National Breast Cancer Coalition (NBCC) is collaborating with the company to
      support trial enrolment and to gain additional insight about ways to improve
      radiation treatment in this patient population. The ENRICH trial protocol was
      approved by the FDA under a Special Protocol Assessment process; as part of the
      protocol, two interim analyses for safety and efficacy will be performed.This
      multicentre, randomised, open-label study has a target enrolment of approximately
      360 patients at >100 medical centres across the US, Canada, Europe and South
      America. Allos announced in September 2004 that recruitment of clinical sites for
      the trial is ongoing across the US and Canada. Completion of trial enrolment in
      North America is anticipated in December 2005. Subsequently, Allos announced in
      January 2005 that recruitment into the ENRICH trial has commenced and is ongoing
      in Europe; enrolment at European sites is expected to conclude by the third
      quarter of 2006. Allos Therapeutics announced in June 2004 that it had filed an
      MAA with the EMEA for marketing of exaproxiral as an adjunct to WBRT for
      treatment of patients with brain metastases originating from breast cancer. The
      application is based on positive data from a pivotal phase III (REACH, RT-009)
      trial in this indication. The completed REACH trial investigated efaproxiral
      among patients with brain metastases undergoing WBRT. The trial was conducted at
      multiple sites in 11 countries, including the US, Canada, Europe and Australia.
      In August 2002 Allos completed the enrolment of 538 patients in the study.
      Initially only 408 patients were to be enrolled, but the company increased the
      size of the trial to conduct an appropriately powered subgroup analysis in
      patients with brain metastases from breast and NSCLC. The study was designed to
      demonstrate a 35% increase in median survival in the subgroup of patients
      compared with standard WBRT alone. The primary endpoint was survival. Allos began
      screening US patients for a phase III trial in NSCLC in early 2003. However, in
      May 2003, the company announced that as part of its revised operating plan it had
      suspended the screening of patients for this trial. The trial, which was known as
      ELITE (Enhanced Lung cancer treatment with Induction chemotherapy and Thoracic
      radiation and Efaproxiral), was comparing induction chemotherapy followed by
      thoracic radiation therapy with supplemental oxygen, with or without efaproxiral.
      The trial was enrolling patients with locally advanced, unresectable NSCLC. ELITE
      was planned to enrol up to 600 patients across North America and Western and
      Eastern Europe. Phase II trials in patients with inoperable NSCLC have been
      conducted in the US and Canada. Patient enrolment in one of these studies was
      completed in August 2000, with a total of 52 patients enrolled. This was an open
      label, multicentre study of induction therapy with paclitaxel plus carboplatin
      followed by chest irradiation and efaproxiral in patients with locally advanced
      NSCLC. Positive results from this study were reported at the annual meeting of
      the European Society for Therapeutics Radiology and Oncology in September 2002.
      Efaproxiral has completed phase I trials as a treatment of surgical hypoxia in
      elective surgery patients receiving general anaesthesia. However, no recent
      development has been reported for these indications. In 1994, Allos signed an
      agreement with CIT for the exclusive worldwide rights to 17 US patents, a
      European patent covering the UK, France, Italy and Germany plus two pending
      patents in these territories, two issued patents in Japan, and a pending patent
      in Canada. These patents cover methods of allosterically modifying haemoglobin
      with efaproxiral and other compounds, the binding site of efaproxiral and therapy
      in certain indications including cancer, ischaemia and hypoxia. In addition to
      the licensed patents from CIT, Allos exclusively owns two patent families with
      pending applications directed to a formulation of efaproxiral and to methods of
      its use in BLOD MRI (blood oxygenation level-dependent magnetic resonance
      imaging) applications. These patents are pending in the US, Canada and Europe,
      and include an international patent application. In a May 2002 interview with the
      Wall Street Transcript, the CEO of Allos estimated the overall market for
      radiation therapy to be approximately 750 000 patients/year. Of this, brain
      metastases, NSCLC and glioblastoma therapy accounts for about 170 000, 140 000
      and 6000 patients, respectively. Allos intend to use a speciality sales force to
      market efaproxiral directly to radiation therapists in North America. To
      penetrate the non-oncology market in the US, the company will seek partnership
      with one or more pharmaceutical companies with direct sales forces and with
      established distribution systems. Allos is also hoping to secure an oncology
      marketing partner for non-North American territories. At the time, the company
      had been issued 21 patents in the US, Canada, Europe and Japan.

PMID- 15869323
TI  - Ramelteon: TAK 375.
AB  - Ramelteon [TAK 375] is a melatonin (MT1/MT2) receptor agonist that is being
      developed by Takeda as a treatment for sleep disorders. It is undergoing
      regulatory review in the US, phase III trials in Europe, and phase II trials in
      Japan for the treatment of insomnia. Phase II trials are also being conducted in
      the US for the treatment of circadian rhythm sleep disordersIn September 2004,
      Takeda submitted an NDA to the US FDA for ramelteon for the treatment of
      insomnia. In May 2003, data presented at the 156th Annual Meeting of the American
      Psychiatric Association report that ramelteon is highly selective for the MT1
      receptor, and has greater affinity, selectivity and potency than melatonin.

PMID- 15869324
TI  - Directed migration of positively selected thymocytes visualized in real time.
AB  - Development of many vertebrate tissues involves long-range cell migrations. In
      most cases, these migrations have been inferred from analysis of single time
      points and the migration process has not been directly observed and quantitated
      in real time. In the mammalian adult thymus, immature CD4+ CD8+ double-positive
      (DP) thymocytes are found in the outer cortex, whereas after T cell antigen
      receptor (TCR) repertoire selection, CD4+ CD8- and CD4- CD8+ single-positive (SP)
      thymocytes are found in the central medulla. Here we have used two-photon laser
      scanning microscopy and quantitative analysis of four-dimensional cell migration
      data to investigate the movement of thymocytes through the cortex in real time
      within intact thymic lobes. We show that prior to positive selection, cortical
      thymocytes exhibit random walk migration. In contrast, positive selection is
      correlated with the appearance of a thymocyte population displaying rapid,
      directed migration toward the medulla. These studies provide our first glimpse
      into the dynamics of developmentally programmed, long-range cell migration in the
      mammalian thymus.

PMID- 15869325
TI  - A scan for positively selected genes in the genomes of humans and chimpanzees.
AB  - Since the divergence of humans and chimpanzees about 5 million years ago, these
      species have undergone a remarkable evolution with drastic divergence in anatomy
      and cognitive abilities. At the molecular level, despite the small overall
      magnitude of DNA sequence divergence, we might expect such evolutionary changes
      to leave a noticeable signature throughout the genome. We here compare 13,731
      annotated genes from humans to their chimpanzee orthologs to identify genes that
      show evidence of positive selection. Many of the genes that present a signature
      of positive selection tend to be involved in sensory perception or immune
      defenses. However, the group of genes that show the strongest evidence for
      positive selection also includes a surprising number of genes involved in tumor
      suppression and apoptosis, and of genes involved in spermatogenesis. We
      hypothesize that positive selection in some of these genes may be driven by
      genomic conflict due to apoptosis during spermatogenesis. Genes with maximal
      expression in the brain show little or no evidence for positive selection, while
      genes with maximal expression in the testis tend to be enriched with positively
      selected genes. Genes on the X chromosome also tend to show an elevated tendency
      for positive selection. We also present polymorphism data from 20 Caucasian
      Americans and 19 African Americans for the 50 annotated genes showing the
      strongest evidence for positive selection. The polymorphism analysis further
      supports the presence of positive selection in these genes by showing an excess
      of high-frequency derived nonsynonymous mutations.

PMID- 15869326
TI  - Control of DNA hybridization with photocleavable adducts.
AB  - Previous reports have shown that 1-(4,5-dimethoxy-2-nitrophenyl)ethyl ester
      (DMNPE) adducts coupled to DNA plasmids block transcription in vitro and in vivo
      until removed with light. In this report, we explore the use of DMNPE to control
      DNA hybridization. We found that DMNPE-caged oligonucleotides have changed
      spectrophotometric and electrophoretic properties that can be restored with light
      exposure. Caged oligonucleotides have slower electrophoretic mobility than
      noncaged oligonucleotides and caged oligonucleotides exposed to light. Effects of
      caging on hybridization were assessed in a fluorescence-based assay using a 20mer
      caged DNA oligonucleotide complementary to a 30mer molecular beacon. Fluorescence
      results indicate that hybridization is reduced and subsequently restored by
      light. Subsequent gel shift assays confirmed these results. Hybridization
      activity of caged oligonucleotides with an average of 14-16 DMNPE adducts per
      oligonucleotide was 14% of noncaged control oligonucleotides and after 365 nm
      photolysis, increased to nearly 80% of controls. Spectrophotometric
      characterization of caged oligonucleotides exposed to light and then filtered to
      remove the released DMNPE adducts indicates two to four attached cage groups
      remaining following photoactivation. These results suggest that this light-based
      technology can be used as a tool for the spatial and temporal regulation of
      hybridization-based DNA bioactivity.

PMID- 15869327
TI  - Raman spectroscopy in combination with background near-infrared autofluorescence
      enhances the in vivo assessment of malignant tissues.
AB  - The diagnostic ability of optical spectroscopy techniques, including near
      infrared (NIR) Raman spectroscopy, NIR autofluorescence spectroscopy and the
      composite Raman and NIR autofluorescence spectroscopy, for in vivo detection of
      malignant tumors was evaluated in this study. A murine tumor model, in which
      BALB/c mice were implanted with Meth-A fibrosarcoma cells into the subcutaneous
      region of the lower back, was used for this purpose. A rapid-acquisition
      dispersive-type NIR Raman system was employed for tissue Raman and NIR
      autofluorescence spectroscopic measurements at 785-nm laser excitation. High
      quality in vivo NIR Raman spectra associated with an autofluorescence background
      from mouse skin and tumor tissue were acquired in 5 s. Multivariate statistical
      techniques, including principal component analysis (PCA) and linear discriminant
      analysis (LDA), were used to develop diagnostic algorithms for differentiating
      tumors from normal tissue based on their spectral features. Spectral
      classification of tumor tissue was tested using a leave-one-out, cross-validation
      method, and the receiver operating characteristic (ROC) curves were used to
      further evaluate the performance of diagnostic algorithms derived. Thirty-two in
      vivo Raman, NIR fluorescence and composite Raman and NIR fluorescence spectra
      were analyzed (16 normal, 16 tumors). Classification results obtained from cross
      validation of the LDA model based on the three spectral data sets showed
      diagnostic sensitivities of 81.3%, 93.8% and 93.8%; specificities of 100%, 87.5%
      and 100%; and overall diagnostic accuracies of 90.6%, 90.6% and 96.9%
      respectively, for tumor identification. ROC curves showed that the most effective
      diagnostic algorithms were from the composite Raman and NIR autofluorescence
      techniques.

PMID- 15869328
TI  - Photoreaction between benzoylthiophenes and N-BOC-tryptophan methyl ester.
AB  - Drug-induced photoallergy requires as the first step formation of covalent drug
      protein photoadducts. One of the key amino acids involved in this process is
      tryptophan (Trp). In this context, several diaryl ketones, including 2
      benzoylthiophene (BT), [2-(5-benzoyl-5-thienyl)]-2-methylpropanoic methyl ester
      (TPA methyl ester) and 4-(2-thienylcarbonyl)phenyl]-2-methylpropanoic methyl
      ester (SUP methyl ester) have been irradiated in the presence of N-BOC-(L)
      tryptophan methyl ester. Laser flash photolysis has allowed to detect three
      neutral radicals (ketyl, indolyl and skatolyl radicals) resulting from formal
      hydrogen-atom abstraction. This correlates well with the isolation of homodimers,
      as well as with cross-coupling products, in the preparative irradiation. The main
      cross-coupling products were in all cases lactones arising from the reaction of
      the Trp-derived skatolyl radicals with the corresponding ketyl radicals. These
      lactones were obtained as the (4R) stereoisomers with remarkable
      diasteroselectivity. No coupling products through the phenyl p-position of BT or
      TPA methyl ester were found. By contrast, ketone homodimers and cross-coupling
      products arising from reaction through the thienyl 5-position were obtained when
      using BT and SUP methyl ester; this is very interesting, because stable LAT
      derived products are difficult to isolate.

PMID- 15869329
TI  - Inhibition of mutation and combating the evolution of antibiotic resistance.
AB  - The emergence of drug-resistant bacteria poses a serious threat to human health.
      In the case of several antibiotics, including those of the quinolone and
      rifamycin classes, bacteria rapidly acquire resistance through mutation of
      chromosomal genes during therapy. In this work, we show that preventing induction
      of the SOS response by interfering with the activity of the protease LexA renders
      pathogenic Escherichia coli unable to evolve resistance in vivo to ciprofloxacin
      or rifampicin, important quinolone and rifamycin antibiotics. We show in vitro
      that LexA cleavage is induced during RecBC-mediated repair of ciprofloxacin
      mediated DNA damage and that this results in the derepression of the SOS
      regulated polymerases Pol II, Pol IV and Pol V, which collaborate to induce
      resistance-conferring mutations. Our findings indicate that the inhibition of
      mutation could serve as a novel therapeutic strategy to combat the evolution of
      antibiotic resistance.

PMID- 15869330
TI  - Determination of stromal signatures in breast carcinoma.
AB  - Many soft tissue tumors recapitulate features of normal connective tissue. We
      hypothesize that different types of fibroblastic tumors are representative of
      different populations of fibroblastic cells or different activation states of
      these cells. We examined two tumors with fibroblastic features, solitary fibrous
      tumor (SFT) and desmoid-type fibromatosis (DTF), by DNA microarray analysis and
      found that they have very different expression profiles, including significant
      differences in their patterns of expression of extracellular matrix genes and
      growth factors. Using immunohistochemistry and in situ hybridization on a tissue
      microarray, we found that genes specific for these two tumors have mutually
      specific expression in the stroma of nonneoplastic tissues. We defined a set of
      786 gene spots whose pattern of expression distinguishes SFT from DTF. In an
      analysis of DNA microarray gene expression data from 295 previously published
      breast carcinomas, we found that expression of this gene set defined two groups
      of breast carcinomas with significant differences in overall survival. One of the
      groups had a favorable outcome and was defined by the expression of DTF genes.
      The other group of tumors had a poor prognosis and showed variable expression of
      genes enriched for SFT type. Our findings suggest that the host stromal response
      varies significantly among carcinomas and that gene expression patterns
      characteristic of soft tissue tumors can be used to discover new markers for
      normal connective tissue cells.

PMID- 15869331
TI  - Order information in working memory: an integrative review of evidence from brain
      and behavior.
AB  - Evidence about memory for order information comes from a number of different
      methodologies: human cognition, patient studies, neuroimaging studies, and animal
      lesion and behavioral studies. The present article discusses (a) evidence that
      order and item memory are separable; (b) proposed mechanisms for order memory
      (interitem associations, direct codes, hierarchical codes, feature codes, and
      magnitude codes) and evidence for each; (c) evidence for the neural substrates of
      order memory from patient, neuroimaging, and animal lesion and single-cell
      recording studies; (d) barriers to integration between the disciplines; and (e)
      suggestions for better coordination of efforts between the different disciplines.

PMID- 15869332
TI  - Epigenetic inheritance and the intergenerational transfer of experience.
AB  - Currently, behavioral development is thought to result from the interplay among
      genetic inheritance, congenital characteristics, cultural contexts, and parental
      practices as they directly impact the individual. Evolutionary ecology points to
      another contributor, epigenetic inheritance, the transmission to offspring of
      parental phenotypic responses to environmental challenges-even when the young do
      not experience the challenges themselves. Genetic inheritance is not altered,
      gene expression is. Organismic pathways for such transmission exist. Maternal
      stress during the latter half of a daughter's gestation may affect not only the
      daughter's but also grand-offspring's physical growth. The author argues that
      temperamental variation may be influenced in the same way. Implications for
      theory and research design are presented along with testable predictions.

PMID- 15869333
TI  - Assessment of adult psychopathology: meta-analyses and implications of cross
      informant correlations.
AB  - Assessment of adult psychopathology relies heavily on self-reports. To determine
      how well self-reports agree with reports by "informants" who know the person
      being assessed, the authors examined 51,000 articles published over 10 years in
      52 peer-reviewed journals for correlations between self-reports and "informants"
      reports. Qualifying correlations were found in 108 (0.2%) of the articles. When
      self-reports and informant reports were obtained with parallel instruments, mean
      cross-informant correlations were .681 for substance use, .428 for internalizing,
      and .438 for externalizing problems. When based on different instruments, the
      mean cross-informant correlation was .304. The moderate sizes of the correlations
      argue for systematically obtaining multi-informant data. National survey findings
      were used to illustrate practical ways to obtain and use such data.

PMID- 15869334
TI  - Memory and aging in context.
AB  - Much research has indicated that aging is accompanied by decrements in memory
      performance across a wide variety of tasks and situations. A dominant perspective
      is that these age differences reflect normative changes in the integrity and
      efficiency of the information-processing system. Contextual perspectives of
      development, however, argue for consideration of a broader constellation of
      factors as determinants of both intraindividual change and interindividual
      variation in memory functioning. The validity of the contextual perspective in
      characterizing the relationship between aging and memory is examined through a
      review of studies exploring a variety of alternative mechanisms associated with
      age differences in performance. It is concluded that a more multidimensional
      approach to the study of aging and memory is warranted.

PMID- 15869335
TI  - Do psychosocial and study skill factors predict college outcomes? Comment on
      Robbins et al. (2004).
AB  - Evidence is cited in support of the claim that the results of the meta-analyses
      conducted by S. B. Robbins et al. (2004) are not generalizable to either
      baccalaureate-granting commuter institutions or certain demographically
      identified subgroups of students.

PMID- 15869337
TI  - Empirically supported psychotherapies: comment on Westen, Novotny, and Thompson
      Brenner (2004).
AB  - D. Westen, C. M. Novotny, and H. Thompson-Brenner (2004; see record 2004-15935
      005) suggested that efforts to identify empirically supported treatments are
      misguided because they are based on assumptions that are not appropriate for some
      types of treatment and patients. The authors of this comment argue that Westen
      and colleagues are simply incorrect when they assert that empirically supported
      treatments require that psychopathology must be highly malleable, that treatments
      must be brief, or that the samples studied are unrepresentative of the kinds of
      patients typically encountered in clinical practice--comorbidity is common in
      many clinical trials. Randomized controlled trials remain the most powerful way
      to test notions of causal agency.

PMID- 15869338
TI  - Jousting with straw men: comment on Westen, Novotny, and Thompson-Brenner (2004).
AB  - Empirically supported treatments (ESTs) do not cure every patient, and the
      randomized trial is not a flawless methodology. Upon these often-noted and widely
      accepted points, D. Westen, C. M. Novotny, and H. Thompson-Brenner (2004a; see
      record 2004-15935-005) built a critique of ESTs and EST research. However,
      important work developing effective, clinically relevant treatments for serious
      problems was omitted from the Westen et al. (2004a) review. Little documentation
      was offered for the purported "assumptions" of EST methodology that Westen et al.
      (2004a) criticized; and different review standards were applied to studies
      supporting versus those disagreeing with Westen et al.'s (2004a) views. Finally,
      the correlational research designs proposed as a remedy by Westen et al. (2004a)
      have far more serious weaknesses than randomized trials, thoughtfully applied to
      real-world clinical care.

PMID- 15869340
TI  - Preparation for speeded action as a psychophysiological concept.
AB  - Mental preparation aids performance and induces multiple physiological changes
      that should inform concepts of preparation. To date, however, these changes have
      been interpreted as being due to a global preparatory process (e.g., attention or
      alertness). The authors review psychophysiological and performance investigations
      of preparation. Concepts of the central regulation of action offer an integrative
      framework for understanding the psychophysiology of preparation. If people
      process multiple streams of information concurrently, then preparatory processing
      requires a form of supervisory attention- central regulation to maintain unity of
      action. This concept is consistent with existing psychophysiological results and
      links them to current views of information processing. Conversely,
      psychophysiological measures may provide indices to test concepts within theories
      of the central regulation of action.

PMID- 15869341
TI  - The case for motor involvement in perceiving conspecifics.
AB  - Perceiving other people's behaviors activates imitative motor plans in the
      perceiver, but there is disagreement as to the function of this activation. In
      contrast to other recent proposals (e.g., that it subserves overt imitation,
      identification and understanding of actions, or working memory), here it is
      argued that imitative motor activation feeds back into the perceptual processing
      of conspecifics' behaviors, generating top-down expectations and predictions of
      the unfolding action. Furthermore, this account incorporates recent ideas about
      emulators in the brain-mental simulations that run in parallel to the external
      events they simulate-to provide a mechanism by which motoric involvement could
      contribute to perception. Evidence from a variety of literatures is brought to
      bear to support this account of perceiving human body movement.

PMID- 15869342
TI  - Aging, subjective experience, and cognitive control: dramatic false remembering
      by older adults.
AB  - Recent research suggests that older adults are more susceptible to interference
      effects than are young adults; however, that research has failed to equate
      differences in original learning. In 4 experiments, the authors show that older
      adults are more susceptible to interference effects produced by a misleading
      prime. Even when original learning was equated, older adults were 10 times as
      likely to falsely remember misleading information and were much less likely to
      increase their accuracy by opting not to answer under conditions of free
      responding. The results are well described by a multinomial model that postulates
      multiple modes of cognitive control. According to that model, older adults are
      likely to be captured by misleading information, a form of goal neglect or
      deficit in inhibitory functions.

PMID- 15869343
TI  - Recognition by humans and pigeons of novel views of 3-D objects and their
      photographs.
AB  - Humans and pigeons were trained to discriminate between 2 views of actual 3-D
      objects or their photographs. They were tested on novel views that were either
      within the closest rotational distance between the training views (interpolated)
      or outside of that range (extrapolated). When training views were 60 degrees
      apart, pigeons, but not humans, recognized novel views of actual objects better
      than their pictures. Further, both species recognized interpolated views of both
      stimulus types better than extrapolated views, but a single distinctive geon
      enhanced recognition of novel views only for humans. When training views were 90
      degrees apart, pigeons recognized interpolated views better than extrapolated
      views with actual objects but not with photographs. Thus, pigeons may represent
      actual objects differently than their pictures.

PMID- 15869344
TI  - A mechanism for error detection in speeded response time tasks.
AB  - The concept of error detection plays a central role in theories of executive
      control. In this article, the authors present a mechanism that can rapidly detect
      errors in speeded response time tasks. This error monitor assigns values to the
      output of cognitive processes involved in stimulus categorization and response
      generation and detects errors by identifying states of the system associated with
      negative value. The mechanism is formalized in a computational model based on a
      recent theoretical framework for understanding error processing in humans (C. B.
      Holroyd & M. G. H. Coles, 2002). The model is used to simulate behavioral and
      event-related brain potential data in a speeded response time task, and the
      results of the simulation are compared with empirical data.

PMID- 15869345
TI  - Resolving visual interference during covert spatial orienting: online attentional
      control through static records of prior visual experience.
AB  - Models of attentional control usually describe online shifts in control settings
      that accommodate changing task demands. The current studies suggest that online
      control over distractor exclusion--a core component of visual selection--can be
      accomplished without online shifts in top-down settings. Measurements of target
      discrimination accuracy suggested that the degree of distractor exclusion was
      guided by retinotopic maps of the prior probability of distractor interference at
      the attended locations. These probability maps can be retrieved via object-based
      cues, and they interact with shifts of attention to elicit increased levels of
      distractor exclusion when it is most needed. Thus, static probability maps can
      provide an internal template that guides the resolution of visual interference as
      spatial attention traverses the visual field.

PMID- 15869346
TI  - Competition between endogenous and exogenous orienting of visual attention.
AB  - The relation between reflexive and voluntary orienting of visual attention was
      investigated with 4 experiments: a simple detection task, a localization task, a
      saccade toward the target task, and a target identification task in which
      discrimination difficulty was manipulated. Endogenous and exogenous orienting
      cues were presented in each trial and their validity was manipulated orthogonally
      to examine whether attention mechanisms are mediated by separate systems and
      whether they have additive and independent effects on visual detection and
      discrimination. The results showed that each orienting mechanism developed its
      typical and independent effect in every case except for the difficult
      identification task. A theoretical framework for understanding the relationship
      between endogenous and exogenous orienting of attention is proposed, tested, and
      confirmed.

PMID- 15869347
TI  - Lexical information drives perceptual learning of distorted speech: evidence from
      the comprehension of noise-vocoded sentences.
AB  - Speech comprehension is resistant to acoustic distortion in the input, reflecting
      listeners' ability to adjust perceptual processes to match the speech input. For
      noise-vocoded sentences, a manipulation that removes spectral detail from speech,
      listeners' reporting improved from near 0% to 70% correct over 30 sentences
      (Experiment 1). Learning was enhanced if listeners heard distorted sentences
      while they knew the identity of the undistorted target (Experiments 2 and 3).
      Learning was absent when listeners were trained with nonword sentences
      (Experiments 4 and 5), although the meaning of the training sentences did not
      affect learning (Experiment 5). Perceptual learning of noise-vocoded speech
      depends on higher level information, consistent with top-down, lexically driven
      learning. Similar processes may facilitate comprehension of speech in an
      unfamiliar accent or following cochlear implantation.

PMID- 15869348
TI  - Personal memories for remote historical events: accuracy and clarity of flashbulb
      memories related to World War II.
AB  - One hundred forty-five Danes between 72 and 89 years of age were asked for their
      memories of their reception of the news of the Danish occupation (April 1940) and
      liberation (May 1945) and for their most negative and most positive personal
      memories from World War II. Almost all reported memories for the invasion and
      liberation. Their answers to factual questions (e.g., the weather) were
      corroborated against objective records and compared with answers from a younger
      control group. The older participants were far more accurate than what could be
      predicted on the basis of results from test-retest studies using short delays.
      The "permastore" metaphor (Bahrick, 1984) provides a possible interpretation of
      this discrepancy. Participants with reported ties to the resistance movement had
      more vivid, detailed, and accurate memories than did participants without such
      ties. Ratings of surprise and consequentiality were unrelated to the accuracy and
      clarity of the memories.

PMID- 15869349
TI  - Affective influences on the attentional dynamics supporting awareness.
AB  - Identification of a 1st target stimulus in a rapid serial visual presentation
      sequence leads to transient impairment in report for a 2nd target; this is known
      as the attentional blink (AB). This AB impairment was substantially alleviated
      for emotionally significant target words. AB sparing was not attributable to a
      variety of nonaffective stimulus factors that could result in augmented
      distinctiveness. Arousal value, not the valence of stimulus events, was found to
      be responsible for AB sparing. These results suggest that arousal is associated
      with decreased attentional prerequisites for awareness, enabling emotional
      significance to shape perceptual experience.

PMID- 15869350
TI  - Reduced electrodermal activity in psychopathy-prone adolescents.
AB  - This study tests the hypothesis that psychopathy-prone adolescents show reduced
      anticipatory skin conductance responding. Electrodermal activity was recorded
      while participants anticipated and responded to a 105 dB signaled or unsignaled
      white-noise burst. Using an extreme groups design, the authors used Child
      Psychopathy Scale (D. R. Lynam, 1997) scores from a community sample of 335 male
      adolescents (age 16) to form control (n = 65) and psychopathy-prone (n = 65)
      groups. Significantly more psychopathy-prone participants were nonresponders in
      the signaled anticipatory (p = .014), signaled responsivity (p = .037), and
      unsignaled responsivity (p = .003) conditions compared with controls.
      Anticipatory hyporesponsivity of psychopathy-prone adolescents similar to the
      electrodermal hyporesponsivity found in psychopathic adults suggests that this
      autonomic impairment is present by adolescence and may predispose individuals to
      adult psychopathy.

PMID- 15869351
TI  - Delta plots in the study of individual differences: new tools reveal response
      inhibition deficits in AD/Hd that are eliminated by methylphenidate treatment.
AB  - The authors highlight the utility of distribution-analytical techniques in the
      study of individual differences and clinical disorders. Cognitive deficits
      associated with attention-deficit/hyperactivity disorder (AD/HD) were examined by
      using delta-plot analyses of performance data (reaction time and accuracy)
      obtained through the use of a prototypical conflict task, the Eriksen flanker
      task. In 20 children with AD/HD (compared with matched control participants),
      overall performance measures indicated a marginal performance deficit. Delta-plot
      analyses indicated that performance deficits associated with AD/HD involve
      response inhibition but not automatic response activation. In a within-subjects
      titration study, the response inhibition deficit was eliminated by
      methylphenidate treatment, but these effects were highly dose specific. The
      beneficial effect of methylphenidate was clarified further after correcting for
      inter-individual variation in sensitivity to medicine dosage.

PMID- 15869352
TI  - A meta-analytic review of stopping performance in attention-deficit/hyperactivity
      disorder: deficient inhibitory motor control?
AB  - This review discusses whether deficient inhibitory motor control is the core
      deficit of attention-deficit/hyperactivity disorder (ADHD). Inhibitory motor
      control is commonly assessed using the stop-signal paradigm. Since the last meta
      analysis that was performed, 33 new studies have appeared. The current meta
      analysis revealed a significant difference between ADHD patients and matched
      controls in stop latency (stop-signal reaction time) in both children and adults.
      Basic reaction time was significantly longer in children with ADHD, but not in
      adults, and there was a significant interaction between the elongation of the
      latency to stop and to respond in adults, but not in children. Deficient
      inhibitory motor control may be less crucial in children than in adults with
      ADHD.

PMID- 15869353
TI  - Hangover frequency and risk for alcohol use disorders: evidence from a
      longitudinal high-risk study.
AB  - Data from a prospective high-risk study (N=489; 51% with a family history of
      alcoholism) were used to test whether family history is associated with greater
      hangover proneness and whether hangover is a risk factor for alcohol use
      disorders. Hangover was more frequent in family-history-positive participants
      during the college years. Persons with an alcohol diagnosis showed excess
      hangover before earning a diagnosis. Year 1 hangover predicted alcohol use
      disorders at Years 7 and 11, even when family history, sex, Year 1 diagnoses, and
      Year 1 drinking were statistically controlled. Several nonhangover drinking
      symptoms failed to predict later diagnoses. Taken together, the findings suggest
      a need for further research and theory on the role of hangover in the etiology of
      drinking problems.

PMID- 15869354
TI  - Speeded detection and increased distraction in fear of spiders: evidence from eye
      movements.
AB  - Anxiety patients exhibit attentional biases toward threat, which have often been
      demonstrated as increased distractibility by threatening stimuli. In contrast,
      speeded detection of threat has rarely been shown. Therefore, the authors studied
      both phenomena in 3 versions of a visual search task while eye movements were
      recorded continuously. Spider-fearful individuals and nonanxious control
      participants participated in a target search task, an odd-one-out search task,
      and a category search task. Evidence for disorder-specific increased distraction
      by threat was found in all tasks, whereas speeded threat detection did not occur
      in the target search task. The implications of these findings for cognitive
      theories of anxiety are discussed, particularly in relation to the concept of
      disengagement from threat.

PMID- 15869355
TI  - Sleep-related attentional bias in good, moderate, and poor (primary insomnia)
      sleepers.
AB  - Evidence was sought of an attentional bias toward a highly representative object
      of the bedroom environment in good, moderate, and poor (primary insomnia)
      sleepers. Using a flicker paradigm for inducing change blindness, the authors
      briefly presented a single scene comprising a group of bedroom environment and
      neutral objects to participants and then briefly replaced this scene with an
      identical scene containing a change made to either a bedroom environment or a
      neutral object. In a 3 x 2 entirely between-participants design, change-detection
      latencies revealed a sleep-related attentional bias in poor sleepers but not in
      good sleepers. A possible bias in moderate sleepers was also revealed. It is
      suggested that attentional bias has a role in the perpetuation and possibly
      precipitation of primary insomnia.

PMID- 15869356
TI  - Posttraumatic stress disorder symptomatology among partners of men in treatment
      for relationship abuse.
AB  - This longitudinal study examined posttraumatic stress disorder (PTSD) symptoms
      among current and former female partners (N = 96) of men participating in a group
      treatment program for partner abuse perpetrators. Female partner probable PTSD
      rates, obtained during time points corresponding with pretreatment,
      posttreatment, and 6-month follow-up for the male clients, were 52%, 34%, and
      29%, respectively. Psychological abuse exposure was more strongly and uniquely
      associated with PTSD symptoms than was physical abuse exposure. Among
      psychological abuse ratings, denigration, restrictive engulfment, and
      dominance/intimidation behaviors evidenced the strongest associations with PTSD
      symptoms. Findings from this study suggest the association between psychological
      abuse and PTSD is complex and multidetermined.

PMID- 15869357
TI  - Cognitive impairments and disordered speech in schizophrenia: thought disorder,
      disorganization, and communication failure perspectives.
AB  - This article posits that basic cognitive impairments in schizophrenia are more
      highly related to speech disorder measured as communication failures than speech
      disorder measured as thought disorder or disorganization. The author tested 47
      schizophrenia patients and 36 control participants for sustained attention,
      sequencing, and conceptual sequencing ability. Their speech was also rated for
      communication failures, thought disorder, and conceptual disorganization.
      Attention and sequencing impairments, examined hierarchically, explained a
      substantial 38% of the variance in the communication measure of speech disorder
      but little of the variance in formal thought disorder or conceptual
      disorganization. The author concludes that (a) impairments in attention and
      sequencing abilities contribute substantially to schizophrenic communication
      failures, and (b) it is important to consider lower level cognitive "3rd
      variables" when examining higher level cognitive associates of speech disorder.

PMID- 15869358
TI  - Working memory consolidation is abnormally slow in schizophrenia.
AB  - This study reports evidence that patients with schizophrenia demonstrate a
      slowing of working memory (WM) consolidation, which is the process of
      transforming transient perceptual representations into durable WM
      representations. Sixteen schizophrenia patients and 16 healthy control
      participants performed a task measuring the visual WM consolidation rate in a
      change-detection paradigm. A target display containing 3 colored squares was
      followed by a variable delay of 17-483 ms, a pattern mask, and then a test
      stimulus. This pattern mask does not interfere with perception but disrupts WM
      consolidation. Control participants reached no-mask performance by 250 ms,
      indicating completed WM consolidation, whereas patients failed to reach no-mask
      performance by 483 ms. Slowed consolidation may play an important and largely
      unrecognized role in schizophrenia.

PMID- 15869359
TI  - Four studies on how past and current suicidality relate even when "everything but
      the kitchen sink" is covaried.
AB  - T. E. Joiner's (2004, in press) theory of suicidal behavior suggests that past
      suicidal behavior plays an important role in future suicidality. However, the
      mechanism by which this risk is transferred and the causal implications have not
      been well studied. The current study provides evaluation of the nature and limits
      of this relationship across 4 populations, with varying degrees of suicidal
      behavior. Across settings, age groups, and impairment levels, the association
      between past suicidal behavior and current suicidal symptoms held, even when
      controlling for strong covariates like hopelessness and symptoms of various Axis
      I and II syndromes. Results provide additional support for the importance of past
      suicidality as a substantive risk factor for later suicidal behavior.

PMID- 15869360
TI  - An implicit test of the associations between children and sex in pedophiles.
AB  - Pedophiles are motivated to disguise their thoughts and feelings about their
      sexual beliefs and attraction toward children. New developments using implicit
      measures of associations have been successful in accessing socially stigmatic
      beliefs, even in cases in which the participant is resistant to this disclosure.
      Using an implicit measure, the authors show that pedophiles have an association
      between children and sex, whereas nonpedophilic offenders have an association
      between adults and sex. The task can therefore identify a core cognitive
      abnormality that may underpin some pedophilic deviant sexual behavior.

PMID- 15869361
TI  - Information-processing biases in young adults from bereaved and divorced
      families.
AB  - Parental loss or divorce is associated with increased risk for affective
      disorders, potentially because of dysfunctional information processing. This
      study evaluated attentional biases to threat or loss-related cues in young adults
      from divorced, parental-loss, or intact families. Participants from intact
      families showed avoidance of supraliminal threat and loss cues, whereas those
      from divorced families showed vigilance toward loss cues. Those from bereaved
      families showed no pattern of bias. Abuse and poor family relationships were
      associated independently with vigilance toward negative cues. After controlling
      for abuse, group differences in threat bias were no longer apparent. Results
      suggest that parental death or divorce may increase risk of affective disorder
      owing to the loss of a "protective bias" away from negative stimuli.

PMID- 15869362
TI  - Attentional biases to internal and external sources of potential threat in social
      anxiety.
AB  - D. M. Clark and A. Wells (1995) proposed that a shift of attention inward toward
      interoceptive information is a central feature of social phobia. However, few
      studies have examined attentional biases toward internal physiological cues in
      social phobia. The current experiment assessed whether socially anxious
      individuals exhibit an attentional bias (a) toward cues for an internal source of
      potential threat (heart-rate information), (b) toward cues for an external source
      of potential threat (threatening faces) or (c) both. Ninety-one participants who
      were selected to form extreme groups based on a social anxiety screening measure
      performed a dot-probe task to assess location of attention. Results showed that
      socially anxious participants exhibited an attentional bias toward cues of
      internal, but not external, sources of potential threat.

PMID- 15869363
TI  - Validating a distinction between primary and secondary psychopathy with measures
      of Gray's BIS and BAS constructs.
AB  - Investigators commonly distinguish between primary and secondary psychopathy (H.
      Cleckley, 1976; D.T. Lykken, 1995), though there is a lack of consensus regarding
      the best means to achieve this distinction. To address the validity of using R.
      D. Hare's (2003) Psychopathy Checklist and the G. Welsh (1956) Anxiety Scale for
      this purpose, the authors used 2 measures of J. A. Gray's (1987) behavioral
      inhibition system/behavioral activation system (BIS/BAS). Following D. T. Lykken
      (1995) and D. C. Fowles (1980), the authors hypothesized that primary psychopathy
      would be associated with a weak BIS and a normal BAS, whereas secondary
      psychopathy would be associated with a strong BAS and a normal BIS. Results for
      primary psychopathy were as predicted. Results for secondary psychopathy clearly
      supported the strong BAS prediction but provided mixed support for the normal BIS
      prediction.

PMID- 15869364
TI  - Use it or lose it: is de-skilling evidence-based?
AB  - 'De-skilling' is a buzzword applied to the alleged attrition of skills through
      their infrequent practice. However, the belief that continuing competence in
      procedural medicine requires the consistent practice of a minimum number of
      procedures is based on anecdotal evidence. This not withstanding, accreditation
      or continuing practice requirements are imposed, often specifying a number of
      procedures that must be performed each year in order to retain the right to
      perform them. The following is a review of the literature into the evaluation of
      procedural skill competence as is related to use.

PMID- 15869365
TI  - Hypothetical model of the financial impact of student attachments on rural
      general practices.
AB  - BACKGROUND: Is teaching a medical student always a financial burden on rural
      general practice? If so, is the current trend towards increasing placement of
      students in rural practice sustainable? Retrospective studies of short-term
      attachments to rural general practice have repeatedly shown a financial cost to
      the practice. Might the results be different for extended attachments? This paper
      presents the results of a small prospective study of the financial impact of
      undergraduate medical students undertaking the Parallel Rural Community
      Curriculum, a 12 month clinical attachment to rural general practice in the
      Riverland region of South Australia. METHODS: Students and doctors involved in
      the program kept separate logs of patient contact time. These data were
      triangulated with third-party direct observation of consultations and an exit
      questionnaire on patient satisfaction. RESULTS: In this study, where students had
      already been actively involved in all aspects of the practice for at least 5
      months, it was found that students had a positive effect on general practitioner
      productivity, without any loss in patient satisfaction. DISCUSSION: To account
      for these findings, a hypothetical model has been developed of the financial
      impact of a student on a rural general practice over time. With the current trend
      in medical schools to undertake increasing amounts of teaching in rural general
      practice, it is suggested that it may be more economically sustainable if
      curricula are adapted to allow extended attachments, likely to be at least 5-6
      months, rather than traditional shorter rotations.

PMID- 15869366
TI  - The impact of health system reform on remote health in Cambodia and the
      Philippines.
AB  - Remoteness is commonly conceived of in the Western health context in terms of
      geographical or social isolation. These features of remoteness also apply to the
      developing nation context. However, the international context has additional
      dimensions of remoteness that impact significantly on health outcomes. These are
      the economic, social and political realities of poverty and insecurity in remote
      populations. Based on the experiences of implementation of health development
      projects in Cambodia and The Philippines in the 1990's, this paper describes the
      character of poverty and insecurity and it's impact on health outcomes. It also
      describes recent health sector reforms of decentralisation and devolution, and
      discusses the degree to which these reforms have responded to the health needs of
      remote populations. CONCLUSION: Poverty and insecurity are dominant factors in
      reducing access to essential health services and hence impact negatively on
      health outcomes, particularly for women and children. Recent health sector
      reforms have not as yet demonstrated tangible benefits for the health of remote
      populations.

PMID- 15869367
TI  - Rural intern training.
AB  - In recent times, legislative initiatives in Australia have changed the method by
      which doctors enter general practice. One result of this tightening has been to
      restrict the access of junior doctors to medical experiences outside the hospital
      environment, and force a closer examination of the 'generalist training' provided
      to junior doctors. The Australian Medical Training Review Panel, created as part
      of these legislative changes, developed a series of recommendations about general
      training in 1996, one of which was to provide for rural and community experiences
      for junior doctors. This article describes the experience of a 'rural intern'
      rotation from Flinders Medical Centre to the rural community of Jamestown, in
      South Australia.

PMID- 15869368
TI  - Report of a medical mission to Somaliland, 2001.
AB  - Somaliland is a self-declared state, not recognized by the nations of the world.
      Sixty percent of the population are herders or small scale farmers. Gross
      national product and other data are not available, but it is evident, according
      to surveys conducted by the United Nations, that most of the population has a low
      income. The health-care system consists of a public sector, which covers primary
      care, hospital care, immunizations, and tuberculosis care. The major clinical
      problems are tuberculosis, malaria and childhood diarrhea. Lack of trained
      personnel is a major difficulty in the health care system. This paper describes
      visits to health care facilities in Somaliland, and suggests some improvements
      for the system.

PMID- 15869369
TI  - Factors influencing student nurses in their choice of a rural clinical placement
      site.
AB  - INTRODUCTION: Rural health and government bodies have identified the need for
      greater numbers of health professionals in rural and remote health care settings.
      Providing students with the opportunity to experience a rural clinical placement
      has been suggested as one strategy for future health professionals to gain
      familiarity with the rural workplace and an awareness of the employment
      opportunities available in these areas. Although substantial numbers of student
      nurses have participated in a rural undergraduate clinical placement program at
      Queensland University of Technology, Australia, since 1996, available places
      remain unfilled. This study aimed to investigate the factors influencing student
      nurses in their choice of a rural or metropolitan clinical placement. METHODS:
      This study utilised a descriptive survey design. In the 24-item questionnaire,
      questions related to demographics, previous experience of a rural lifestyle,
      previous work experience and issues of importance regarding the clinical
      placement experience. All final-year Bachelor of Nursing students in the year
      2000 (n = 212) were included in the sample, with a 65% response rate for the pre
      test (n = 137). Frequency distributions, chi2 analysis (for nominal data) and
      ANOVA (for interval data) were used to describe differences between the
      characteristics of students choosing a rural or remote placement and students
      choosing a metropolitan placement. RESULTS: Findings demonstrated that possession
      of a rural background, previous work experience in a rural community and family,
      financial and/or employment commitments all influenced students' choice of
      undertaking a rural clinical placement. CONCLUSION: Students who have previously
      lived and/or worked in a rural area are more likely to choose a rural setting for
      clinical placements or postgraduate employment. However, the value of rural
      clinical placements as a method of increasing awareness of employment
      opportunities in the rural setting is considerable. Family, financial and
      employment commitments should be considered in the development of recruitment and
      retention strategies for health professionals to rural areas.

PMID- 15869370
TI  - Ambulatory diagnoses-cluster statistics of patient visits at a clinic in the
      Amazon Region of Ecuador.
AB  - INTRODUCTION: Mondana Clinic is a small rural clinic located in the Napo river
      region of the Amazon basin in Ecuador. Since its opening in 1997 the clinic has
      grown to be the primary health care facility for approximately 3000 individuals.
      METHODS: A retrospective study was performed tabulating the ambulatory diagnosis,
      age, sex, and domicile of patients over a 9 month period in 1999. RESULTS: During
      the study period there were 765 patient visits that resulted in at least one
      diagnosis. Of the patient visits, 175 (22.8%) resulted in multiple diagnoses.
      Women accounted for 58% of the patient visits, which is similar to the 60% of
      ambulatory patient visits made in the USA by women. The age distribution showed
      66% of patients were under 25 years of age. When comparing diagnoses of males
      with females, several differences were noted. As expected, urinary tract
      infections were approximately four-fold more common in females than in males.
      Gastritis and headaches were also more common reasons for patient visits in the
      female population than in the male. Conversely, lacerations, abrasions, and
      contusions ranked higher in the male than in the female population for patient
      visits. CONCLUSION: This study is the first to provide public health information
      for this region that will prove useful to the health professionals and funding
      agencies working in the region. Furthermore, it provides a baseline for
      comparison with other regions in Ecuador and South America in general, as well as
      comparisons with data-rich countries such as the USA.

PMID- 15869371
TI  - Rural nursing and health care reforms: building a social model of health.
AB  - This article explores recent shifts in health-care policy and the implications
      for rural nursing in Australia. Health-care reforms have resulted in the
      implementation of a 'market forces' ideology, creating tensions between economic
      imperatives and the need for equity and greater access in rural service delivery.
      New models of health-service delivery have been developed that have significant
      implications for the way rural health care is defined, practised and received.
      The issues surrounding the context of rural nursing practice and service delivery
      are discussed.

PMID- 15869373
TI  - Evidence-based rural general practice: still the evidence is largely absent.

PMID- 15869372
TI  - Towards evidence-based general practice in rural and remote Australia: an
      overview of key issues and a model for practice.
AB  - There is an extensive global move towards evidence-based practice intended to
      increase the quality and effectiveness of health care. However there are barriers
      and issues when rural general practitioners attempt to incorporate evidence-based
      medicine in their practice. Key issues affecting the uptake of evidence-based
      medicine by rural general practitioners include the gaps in the scientific
      evidence relevant to general practice, time limitations, and the cost of Internet
      access, geographical isolation from centres of evidence-based practice and
      limited training opportunities. General practitioner consultations may involve
      multiple, ill-defined problems and the patients' views about their treatment may
      conflict with an evidence-based treatment approach. Rural general practitioners
      may require additional supports to access information from research through
      Internet-based resources, accessible summaries of evidence or clinical practice
      guidelines. In addition a model to assist rural general practitioners use
      evidence-based medicine is suggested. This model may enable the clinical decision
      making process to integrate clinical experience, patient preferences and an
      understanding of the rural context of practice with the best available evidence,
      to in turn produce best practice.

PMID- 15869374
TI  - Impact of medical students on rural preceptors--it's time for better evidence.

PMID- 15869375
TI  - More nurses--better health.

PMID- 15869376
TI  - Modeling water, the hydrophobic effect, and ion solvation.
AB  - Water plays a central role in the structures and properties of biomolecules-
      proteins, nucleic acids, and membranes--and in their interactions with ligands
      and drugs. Over the past half century, our understanding of water has been
      advanced significantly owing to theoretical and computational modeling. However,
      like the blind men and the elephant, different models describe different aspects
      of water's behavior. The trend in water modeling has been toward finer-scale
      properties and increasing structural detail, at increasing computational expense.
      Recently, our labs and others have moved in the opposite direction, toward
      simpler physical models, focusing on more global properties-water's
      thermodynamics, phase diagram, and solvation properties, for example-and toward
      less computational expense. Simplified models can guide a better understanding of
      water in ways that complement what we learn from more complex models. One
      ultimate goal is more tractable models for computer simulations of biomolecules.
      This review gives a perspective from simple models on how the physical properties
      of water-as a pure liquid and as a solvent-derive from the geometric and hydrogen
      bonding properties of water.

PMID- 15869377
TI  - A dual group processes model of individual differences in prejudice.
AB  - The study of right-wing authoritarianism (RWA) and Social Dominance Orientation
      (SDO) as predictors of prejudice has represented an attempt to explain group
      dynamics in terms of individual traits. In contrast, I argue that the individual
      tendencies that predict prejudice are actually a product of group dynamics. This
      article critiques personality approaches, focusing primarily on authoritarianism
      and secondarily on social dominance, and defends a model that explains the 2
      variables in terms of discrete group processes. According to the Dual Group
      Processes model, SDO reflects category differentiation, which involves the
      evaluation of individuals on the basis of their category membership. RWA reflects
      normative differentiation, which involves the evaluation of ingroup members on
      the basis of their prototypicality. Authoritarian aggression-whether against
      ethnic minorities or other targets-is conceptualized as an intragroup phenomenon,
      involving the rejection of perceived antinorm deviants who threaten the longevity
      or legitimacy of social norms.

PMID- 15869378
TI  - Rethinking the link between categorization and prejudice within the social
      cognition perspective.
AB  - For the past 40 years, social psychological research on stereotyping and
      prejudice in the United States has been dominated by the social cognition
      perspective, which has emphasized the important role of basic categorization
      processes in intergroup dynamics. An inadvertent consequence of this approach has
      been a disproportionate focus on social categorization as a causal factor in
      intergroup animosity and, accordingly, an emphasis on approaches that minimize
      category distinctions as the solution to intergroup conflict. Though recognizing
      the crucial function of categorization, we question existing support for the
      hypothesis that the perception of strong group differences necessarily results in
      greater intergroup bias. Given that it is neither feasible nor ultimately
      desirable to imagine that social categories can be eliminated, we suggest that a
      more useful approach is one that promotes intergroup harmony even while
      recognizing and valuing the distinctions that define our social world.

PMID- 15869379
TI  - Teacher expectations and self-fulfilling prophecies: knowns and unknowns,
      resolved and unresolved controversies.
AB  - This article shows that 35 years of empirical research on teacher expectations
      justifies the following conclusions: (a) Self-fulfilling prophecies in the
      classroom do occur, but these effects are typically small, they do not accumulate
      greatly across perceivers or over time, and they may be more likely to dissipate
      than accumulate; (b) powerful self-fulfilling prophecies may selectively occur
      among students from stigmatized social groups; (c) whether self-fulfilling
      prophecies affect intelligence, and whether they in general do more harm than
      good, remains unclear, and (d) teacher expectations may predict student outcomes
      more because these expectations are accurate than because they are self
      fulfilling. Implications for future research, the role of self-fulfilling
      prophecies in social problems, and perspectives emphasizing the power of
      erroneous beliefs to create social reality are discussed.

PMID- 15869380
TI  - Promoting the "social" in the examination of social stigmas.
AB  - This review highlights the value of empirical investigations examining actual
      interactions that occur between stigmatizers and targets, and is intended to
      stimulate and help guide research of this type. We identify trends in the
      literature demonstrating that research studying ongoing interactions between
      stigmatizers and targets is relatively less common than in the past. Interactive
      studies are challenging, complex, and have variables that are sometimes more
      difficult to control; yet, they offer unique insights and significant
      contributions to understanding stigma-related phenomena that may not be offered
      in other (e.g., self-report) paradigms. This article presents a conceptual and
      empirical overview of stigma research, delineates the unique contributions that
      have been made by conducting interactive studies, and proposes what can be
      further learned by conducting more of such research.

PMID- 15869381
TI  - A quiet life with proteins.

PMID- 15869382
TI  - Communication between noncontacting macromolecules.
AB  - Molecular interactions are the language that molecules use to communicate
      recognition, binding, and regulation, events central to biological control
      mechanisms. Traditionally, such interactions involve direct, atom-to-atom,
      noncovalent contacts, or indirect contacts bridged by relatively fixed solvent
      molecules. Here we discuss a third class of molecular communication that, to
      date, has received less experimental attention, namely solvent-mediated
      communication between noncontacting macromolecules. This form of communication
      can be understood in terms of fundamental, well-established principles (coupled
      equilibria and linkage thermodynamics) that govern interactions between
      individual polymers and their solutions. In contrast to simple solutions used in
      laboratory studies, biological systems contain a multitude of nominally
      noninteracting biopolymers within the same solution environment. The exquisite
      control of biological function requires some form of communication between many
      of these solution components, even in the absence of direct and/or indirect
      contacts. Such communication must be considered when describing potential
      mechanisms of biological regulation.

PMID- 15869383
TI  - How well can simulation predict protein folding kinetics and thermodynamics?
AB  - Simulation of protein folding has come a long way in five years. Notably, new
      quantitative comparisons with experiments for small, rapidly folding proteins
      have become possible. As the only way to validate simulation methodology, this
      achievement marks a significant advance. Here, we detail these recent
      achievements and ask whether simulations have indeed rendered quantitative
      predictions in several areas, including protein folding kinetics, thermodynamics,
      and physics-based methods for structure prediction. We conclude by looking to the
      future of such comparisons between simulations and experiments.

PMID- 15869384
TI  - Use of EPR power saturation to analyze the membrane-docking geometries of
      peripheral proteins: applications to C2 domains.
AB  - Despite the central importance of peripheral membrane proteins to cellular
      signaling and metabolic pathways, the structures of protein-membrane interfaces
      remain largely inaccessible to high-resolution structural methods. In recent
      years a number of laboratories have contributed to the development of an electron
      paramagnetic resonance (EPR) power saturation approach that utilizes site
      directed spin labeling to determine the key geometric parameters of membrane
      docked proteins, including their penetration depths and angular orientations
      relative to the membrane surface. Representative applications to Ca(2+)
      activated, membrane-docking C2 domains are described.

PMID- 15869386
TI  - Membrane-protein interactions in cell signaling and membrane trafficking.
AB  - Research in the past decade has revealed that many cytosolic proteins are
      recruited to different cellular membranes to form protein-protein and lipid
      protein interactions during cell signaling and membrane trafficking. Membrane
      recruitment of these peripheral proteins is mediated by a growing number of
      modular membrane-targeting domains, including C1, C2, PH, FYVE, PX, ENTH, ANTH,
      BAR, FERM, and tubby domains, that recognize specific lipid molecules in the
      membranes. Structural studies of these membrane-targeting domains demonstrate how
      they specifically recognize their cognate lipid ligands. However, the mechanisms
      by which these domains and their host proteins are recruited to and interact with
      various cell membranes are only beginning to unravel with recent computational
      studies, in vitro membrane binding studies using model membranes, and cellular
      translocation studies using fluorescent protein-tagged proteins. This review
      summarizes the recent progress in our understanding of how the kinetics and
      energetics of membrane-protein interactions are regulated during the cellular
      membrane targeting and activation of peripheral proteins.

PMID- 15869387
TI  - Ion conduction and selectivity in K(+) channels.
AB  - Potassium (K(+)) channels are tetrameric membrane-spanning proteins that provide
      a selective pore for the conductance of K(+) across the cell membranes. These
      channels are most remarkable in their ability to discriminate K(+) from Na(+) by
      more than a thousandfold and conduct at a throughput rate near diffusion limit.
      The recent progress in the structural characterization of K(+) channel provides
      us with a unique opportunity to understand their function at the atomic level.
      With their ability to go beyond static structures, molecular dynamics simulations
      based on atomic models can play an important role in shaping our view of how ion
      channels carry out their function. The purpose of this review is to summarize the
      most important findings from experiments and computations and to highlight a
      number of fundamental mechanistic questions about ion conduction and selectivity
      that will require further work.

PMID- 15869385
TI  - Chemical synthesis of proteins.
AB  - Proteins have become accessible targets for chemical synthesis. The basic
      strategy is to use native chemical ligation, Staudinger ligation, or other
      orthogonal chemical reactions to couple synthetic peptides. The ligation
      reactions are compatible with a variety of solvents and proceed in solution or on
      a solid support. Chemical synthesis enables a level of control on protein
      composition that greatly exceeds that attainable with ribosome-mediated
      biosynthesis. Accordingly, the chemical synthesis of proteins is providing
      previously unattainable insight into the structure and function of proteins.

PMID- 15869388
TI  - Tracking topoisomerase activity at the single-molecule level.
AB  - The recent development of new techniques to manipulate single DNA molecules has
      opened new opportunities for the study of the enzymes that control DNA topology:
      the type I and II topoisomerases. These single-molecule assays provide a unique
      way to study the uncoiling of single supercoiled DNA molecules and the unlinking
      of two intertwined DNAs. They allow for a detailed characterization of the
      activity of topoisomerases, including the processivity, the chiral
      discrimination, and the dependence of their enzymatic rate on ATP concentration,
      degree of supercoiling, and the tension in the molecule. These results shed new
      light on the mechanism of these enzymes and their function in vivo.

PMID- 15869389
TI  - Ions and RNA folding.
AB  - The problem of how ions influence the folding of RNA into specific tertiary
      structures is being addressed from both thermodynamic (by how much do different
      salts affect the free energy change of folding) and structural (how are ions
      arranged on or near an RNA and what kinds of environments do they occupy) points
      of view. The challenge is to link these different approaches in a theoretical
      framework that relates the energetics of ion-RNA interactions to the spatial
      distribution of ions. This review distinguishes three different kinds of ion
      environments that differ in the extent of direct ion-RNA contacts and the degree
      to which the ion hydration is perturbed, and summarizes the current understanding
      of the way each environment relates to the overall energetics of RNA folding.

PMID- 15869390
TI  - Ligand-target interactions: what can we learn from NMR?
AB  - The conformation of the ligand in complex with a macromolecular target can be
      studied by nuclear magnetic resonance (NMR) in solution for both tightly and
      weakly forming complexes. In the weak binding regime (k(off) > 10(4) Hz), the
      structure of the bound ligand is accessible also for very large complexes (>100
      kDa), which are not amenable to NMR studies in the tight binding regime. Here I
      review the state-of-the-art NMR methodology used for screening ligands and for
      the structural investigation of bound ligand conformations, in both tight and
      weak binding regimes. The advantages and disadvantages of each approach are
      critically described. The NMR methodology used to investigate transiently forming
      complexes has expanded considerably in the past few years, opening new
      possibilities for a detailed description of ligand-target interactions. Novel
      methods for the determination of the bound ligand conformation, in particular
      transferred cross-correlated relaxation, are thoroughly reviewed, and their
      advantages with respect to established methodology are discussed, using the
      epothilone-tubulin complex as a primary example.

PMID- 15869392
TI  - Toroidal DNA condensates: unraveling the fine structure and the role of
      nucleation in determining size.
AB  - Toroidal DNA condensates have attracted the attention of biophysicists,
      biochemists, and polymer physicists for more than thirty years. In the biological
      community, the quest to understand DNA toroid formation has been motivated by its
      relevance to gene packing in certain viruses and by the potential use of DNA
      toroids in artificial gene delivery (e.g., gene therapy). In the physical
      sciences, DNA toroids are appreciated as a superb model system for studying
      particle formation by the collapse of a semiflexible, polyelectrolyte polymer.
      This review focuses on experimental studies from the past few years that have
      significantly increased our understanding of DNA toroid structure and the
      mechanism of their formation. Highlights include structural studies that show the
      DNA strands within toroids to be packed in an ideal hexagonal lattice, and also
      in regions with a nonhexagonal lattice that are required by the topological
      constraints associated with winding DNA into a toroid. Recent studies of DNA
      toroid formation have also revealed that toroid size limits result from a complex
      interplay between kinetic and thermodynamic factors that govern both toroid
      nucleation and growth. The work discussed in this review indicates that it will
      ultimately be possible to obtain substantial control over DNA toroid dimensions.

PMID- 15869391
TI  - Structural and sequence motifs of protein (histone) methylation enzymes.
AB  - With genome sequencing nearing completion for the model organisms used in
      biomedical research, there is a rapidly growing appreciation that proteomics, the
      study of covalent modification to proteins, and transcriptional regulation will
      likely dominate the research headlines in the next decade. Protein methylation
      plays a central role in both of these fields, as several different residues (Arg,
      Lys, Gln) are methylated in cells and methylation plays a central role in the
      "histone code" that regulates chromatin structure and impacts transcription. In
      some cases, a single lysine can be mono-, di-, or trimethylated, with different
      functional consequences for each of the three forms. This review describes
      structural aspects of methylation of histone lysine residues by two enzyme
      families with entirely different structural scaffolding (the SET proteins and
      Dot1p) and methylation of protein arginine residues by PRMTs.

PMID- 15869394
TI  - Paradigm shift of the plasma membrane concept from the two-dimensional continuum
      fluid to the partitioned fluid: high-speed single-molecule tracking of membrane
      molecules.
AB  - Recent advancements in single-molecule tracking methods with nanometer-level
      precision now allow researchers to observe the movement, recruitment, and
      activation of single molecules in the plasma membrane in living cells. In
      particular, on the basis of the observations by high-speed single-particle
      tracking at a frame rate of 40,000 frames s(1), the partitioning of the fluid
      plasma membrane into submicron compartments throughout the cell membrane and the
      hop diffusion of virtually all the molecules have been proposed. This could
      explain why the diffusion coefficients in the plasma membrane are considerably
      smaller than those in artificial membranes, and why the diffusion coefficient is
      reduced upon molecular complex formation (oligomerization-induced trapping). In
      this review, we first describe the high-speed single-molecule tracking methods,
      and then we critically review a new model of a partitioned fluid plasma membrane
      and the involvement of the actin-based membrane-skeleton "fences" and anchored
      transmembrane protein "pickets" in the formation of compartment boundaries.

PMID- 15869395
TI  - Protein-DNA recognition patterns and predictions.
AB  - Structural data on protein-DNA complexes provide clues for understanding the
      mechanism of protein-DNA recognition. Although the structures of a large number
      of protein-DNA complexes are known, the mechanisms underlying their specific
      binding are still only poorly understood. Analysis of these structures has shown
      that there is no simple one-to-one correspondence between bases and amino acids
      within protein-DNA complexes; nevertheless, the observed patterns of interaction
      carry important information on the mechanisms of protein-DNA recognition. In this
      review, we show how the patterns of interaction, either observed in known
      structures or derived from computer simulations, confer recognition specificity,
      and how they can be used to examine the relationship between structure and
      specificity and to predict target DNA sequences used by regulatory proteins.

PMID- 15869396
TI  - Single-molecule RNA science.
AB  - The development of single-molecule detection and manipulation has allowed us to
      monitor the behavior of individual biological molecules and molecular complexes
      in real time. This approach significantly expands our capability to characterize
      complex dynamics of biological processes, allowing transient intermediate states
      and parallel kinetic pathways to be directly observed. Exploring this capability
      to elucidate complex dynamics, recent single-molecule experiments on RNA folding
      and catalysis have improved our understanding of the folding energy landscape of
      RNA and allowed us to better dissect complex RNA catalytic reactions, including
      translation by the ribosome.

PMID- 15869397
TI  - The structure-function dilemma of the hammerhead ribozyme.
AB  - A powerful approach to understanding protein enzyme catalysis is to examine the
      structural context of essential amino acid side chains whose deletion or
      modification negatively impacts catalysis. In principle, this approach can be
      even more powerful for RNA enzymes, given the wide variety and subtlety of
      functionally modified nucleotides now available. Numerous recent success stories
      confirm the utility of this approach to understanding ribozyme function. An
      anomaly, however, is the hammerhead ribozyme, for which the structural and
      functional data do not agree well, preventing a unifying view of its catalytic
      mechanism from emerging. To delineate the hammerhead structure-function
      comparison, we have evaluated and distilled the large body of biochemical data
      into a consensus set of functional groups unambiguously required for hammerhead
      catalysis. By examining the context of these functional groups within available
      structures, we have established a concise set of disagreements between the
      structural and functional data. The number and relative distribution of these
      inconsistencies throughout the hammerhead reaffirms that an extensive
      conformational rearrangement from the fold observed in the crystal structure must
      be necessary for cleavage to occur. The nature and energetic driving force of
      this conformational isomerization are discussed.

PMID- 15869406
TI  - Effects of multiple copies of CpG on DNA vaccination.
AB  - It has previously been demonstrated that a dose-dependent enhancement of immune
      response is derived from immunization with several copies of the CpG motif.
      Following that lead, we sought to incorporate a higher copy number of CpG motifs
      into an expression construct to evaluate the augmentation of immune responses. By
      multiple insertions, 30 copies of the CpG motif were cloned into the backbone of
      an expression construct encoding the foot-and-mouth disease virus (FMDV) capsid
      protein VP1. After intramuscular immunization, an augmented immune response with
      significantly increased levels of the specific antibody, T-cell proliferation,
      and IFN-gamma in Balb/c mice was observed. Compared to chemically synthesized CpG
      ODN, application of such a multicopy of CpG sequences within the expression
      backbone for DNA vaccination strategy is feasible and warranted.

PMID- 15869404
TI  - Receptor-targeted cancer therapy.
AB  - Insight into the molecular mechanisms of malignant transformation is changing the
      way cancer is being treated. Conventional treatment strategies target the DNA of
      all dividing cells, resulting in a significantly increased risk of collateral
      toxicity. In addition, the accumulation of multiple mutations leads to drug
      resistance in many cancer cells. Targeted strategies have now been developed that
      specifically disrupt oncogenically active cell surface receptors and endogenous
      signaling molecules. These agents have a much greater selectivity for tumor
      tissue and decreased risk of side effects. Increased signaling through ErbB
      receptors via gene amplification, overexpression, and mutation has been
      implicated in many human cancers and associated with poor prognosis. Interruption
      of this process has been shown to cause antitumor effects. Downregulation of the
      ErbB receptors, HER-2/neu, and later EGFR, with monoclonal antibodies was the
      first demonstration of targeted therapy. Subsequently, the ErbB tyrosine kinase
      domain has been successfully targeted with small molecule inhibitors. The
      development of novel ErbB-directed entities is ongoing, with particular promise
      being shown by strategies targeting receptor interaction in oligomeric complexes.

PMID- 15869393
TI  - Toward predictive models of mammalian cells.
AB  - Progress in experimental and theoretical biology is likely to provide us with the
      opportunity to assemble detailed predictive models of mammalian cells. Using a
      functional format to describe the organization of mammalian cells, we describe
      current approaches for developing qualitative and quantitative models using data
      from a variety of experimental sources. Recent developments and applications of
      graph theory to biological networks are reviewed. The use of these qualitative
      models to identify the topology of regulatory motifs and functional modules is
      discussed. Cellular homeostasis and plasticity are interpreted within the
      framework of balance between regulatory motifs and interactions between modules.
      From this analysis we identify the need for detailed quantitative models on the
      basis of the representation of the chemistry underlying the cellular process. The
      use of deterministic, stochastic, and hybrid models to represent cellular
      processes is reviewed, and an initial integrated approach for the development of
      large-scale predictive models of a mammalian cell is presented.

PMID- 15869405
TI  - Nanosecond pulsed electric fields (nsPEF) induce direct electric field effects
      and biological effects on human colon carcinoma cells.
AB  - Nanosecond pulsed electric fields (nsPEFs) are ultrashort pulses with high
      electric field intensity (kV/cm) and high power (megawatts), but low energy
      density (mJ/cc). To determine roles for p53 in response to nsPEFs, HCT116 cells
      (p53+/+ and p53-/-) were exposed to nsPEF and analyzed for membrane integrity,
      phosphatidylserine externalization, caspase activation, and cell survival.
      Decreasing plasma membrane effects were observed in both HCT116p53+/+ and p53-/-
      cells with decreasing pulse durations and/or decreasing electric fields. However,
      addition of ethidium homodimer-1 and Annexin-V-FITC post-pulse demonstrated
      greater fluorescence in p53-/- versus p53+/+ cells, suggesting a postpulse p53
      dependent biological effect at the plasma membrane. Caspase activity was
      significantly higher than nonpulsed cells only in the p53-/- cells. HCT116 cells
      exhibited greater survival in response to nsPEFs than HL-60 and Jurkat cells, but
      survival was more evident for HCT116p53+/+ cells than for HCT116p53-/- cells.
      These results indicate that nsPEF effects on HCT116 cells include (1) apparent
      direct electric field effects, (2) biological effects that are p53-dependent and
      p53-independent, (3) actions on mechanisms that originate at the plasma membranes
      and at intracellular structures, and (4) an apparent p53 protective effect. NsPEF
      applications provide a means to explore intracellular structures and functions
      that can reveal mechanisms in health and disease.

PMID- 15869407
TI  - Different roles of Sp family members in HIV-1 Tat-mediated manganese superoxide
      dismutase suppression in hepatocellular carcinoma cells.
AB  - The expression of manganese superoxide dismutase (MnSOD) is regulated by agents
      associated with cancer development. It has been shown that infection with the
      human immunodeficiency virus type 1 (HIV-1) is associated with the development of
      liver cancer and that the transactivating transcriptional factor (Tat) of human
      HIV-1 reduces the expression of MnSOD in several cell types. However, the role of
      Tat in the expression of MnSOD in hepatocellular carcinoma is unknown.
      Furthermore, the precise mechanisms whereby Tat suppresses MnSOD expression in
      hepatocellular carcinoma cells remain unclear. In this report, we build on our
      original observations that Tat changes the distribution of Sp family members on
      the MnSOD promoter, which accounts for Tat-dependent changes in basal expression.
      In hepatic cells, Tat expression upregulates Sp1/Sp3, which play different roles
      in regulating MnSOD transcription. While overexpression of Sp1 stimulates,
      overexpression of Sp3 represses transcriptional activity. The transcription
      repression effect of Sp3 is not due to Sp3 competing for the binding site with
      Sp1 because only the full-length Sp3 but not the truncated Sp3 suppresses MnSOD
      promoter activity. These findings suggest a novel mechanism by which Tat
      modulates the repression of the MnSOD gene and establish a link between HIV
      infection and liver cancer.

PMID- 15869408
TI  - Expression of c-Fes protein isoforms correlates with differentiation in myeloid
      leukemias.
AB  - The cellular fes gene encodes a 93-kilodalton protein-tyrosine kinase (p93) that
      is expressed in both normal and neoplastic myeloid cells. Increased c-Fes
      expression is associated with differentiation in normal myeloid cells and cell
      lines. Our hypothesis was that primary leukemia cells would show a similar
      pattern of increased expression in more differentiated cells. Therefore, we
      compared c-Fes expression in cells with an undifferentiated, blast phenotype
      (acute myelogenous leukemia--AML) to cells with a differentiated phenotype
      (chronic myelogenous leukemia--CML). Instead of differences in p93 expression
      levels, we found complex patterns of c-Fes immunoreactive proteins that
      corresponded with differentiation in normal and leukemic myeloid cells. The
      "blast" pattern consisted of c-Fes immunoreactive proteins p93, p74, and p70; the
      "differentiated" pattern showed two additional c-Fes immunoreactive proteins, p67
      and p62. Using mRNA from mouse and human cell lines, we found deletion of one or
      more exons in the c-fes mRNA. Those deletions predicted truncation of conserved
      domains (CDC15/FCH and SH2) involved in protein-protein interactions. No
      deletions were found, however, within the kinase domain. We infer that
      alternative splicing generates a family of c-Fes proteins. This may be a
      mechanism to direct the c-Fes kinase domain to different subcellular locations
      and/or substrates at specific stages of myeloid cell differentiation.

PMID- 15869409
TI  - Induction of antigen-specific immune responses against malignant brain tumors by
      intramuscular injection of sindbis DNA encoding gp100 and IL-18.
AB  - We constructed pSin-SV40-HDV-SV40pA, an improved Sindbis DNA expression vector,
      and evaluated the potential of this vector system for brain tumor therapy. We
      investigated whether immunizing mice with xenogeneic DNA encoding human gp100 and
      mouse IL-18 would enhance the antitumor responses. To study the immune mechanisms
      involved in tumor regression, we examined tumor growth in B16-gp100-implanted
      brain tumor models using T-cell subset-depleted and IFN-gamma-neutralized mice.
      Hugp100/mIL-18 vaccination was also investigated for its antitumor effects
      against the wild-type murine B16 tumor, which expresses the murine gp100
      molecule. Genetic immunization using plasmid pSin 9001 DNA codelivery of human
      gp100 and mouse IL-18 resulted in enhanced protective and therapeutic effects on
      the malignant brain tumors. The antitumor and protective effects were mediated by
      both CD4(+)/CD8(+) T cells and IFN-gamma. Vaccination with hugp100/mIL-18
      conferred a significant survival merit to wild-type B16 tumor-harboring mice.
      Immunogene therapy with the improved Sindbis virus vector expressing xenogeneic
      gp100 and syngeneic IL-18 may be an excellent approach for developing a new
      treatment protocol. Thus, the Sindbis DNA system may represent a novel approach
      for the treatment of malignant brain tumors.

PMID- 15869414
TI  - California's Proposition 71.

PMID- 15869411
TI  - Skeletrophin, a novel RING molecule controlled by the chromatin remodeling
      complex, is downregulated in malignant melanoma.
AB  - Recent experiments have revealed that aberrant functionality of the chromatin
      remodeling complex is related to tumorigenicity in various malignant tumors.
      Skeletrophin is an actin-binding cytoskeleton-related molecule, which is induced
      by the overexpression of truncated human SWI1 (SMARCF1). Human SWI1 is a sub-unit
      of the chromatin remodeling complex and binds chromatin through its ARID (AT-rich
      interactive domain). Truncated SWI1 lacks one of the two glucocorticoid-receptor
      binding domains and inhibits the intact human SWI1 in a dominant negative manner.
      Skeletrophin, was therefore identified as a candidate molecule for the indication
      of change to a malignant phenotype due to the aberrant function of the chromatin
      remodeling complex. Surprisingly, the skeletrophin gene is located in 1p36.32,
      where the putative tumor suppressor gene of cutaneous malignant melanoma has long
      been postulated to be on. Cutaneous malignant melanoma is a highly aggressive
      tumor. To overcome the clinical problem of malignant melanoma and highly invasive
      and metastatic activity, it is important to unravel the molecular mechanism
      responsible for melanoma progression. Recent studies including those from our
      laboratories have elucidated that skeletrophin is a novel RING-HC type ubiquitin
      ligase and that the ubiquitin ligase pathway mediated by skeletrophin acts to
      oppose melanoma cell invasion. Here, we summarize the characterization of
      skeletrophin, with emphasis on its biological activity, the disruption of which
      is linked with melanoma progression.

PMID- 15869415
TI  - In vitro, in vivo, in silico: computational systems in tissue engineering and
      regenerative medicine.
AB  - The emergence of computational systems in tissue engineering and regenerative
      medicine is paralleling the rapid rise of new technology. Developments in
      software and hardware have allowed access to the huge data streams that are now
      available. The Human Genome Project led the way and opened many avenues for other
      branches of science and biology with extensive but contained databanks. The
      availability of vast amounts of data means nothing without the ability to
      integrate the information into a useful form. Tissue engineering has always been
      a practical science in which function and utility are key objectives. This review
      delineates key areas of this rapidly ascending branch of science and illustrates
      examples central to the successful integration of computational methods.

PMID- 15869410
TI  - The human AKNA gene expresses multiple transcripts and protein isoforms as a
      result of alternative promoter usage, splicing, and polyadenylation.
AB  - We previously showed that the human AKNA gene encodes an AT-hook transcription
      factor that regulates the expression of costimulatory cell surface molecules on
      lymphocytes. However, AKNA cDNA probes hybridize with multiple transcripts,
      suggesting either the existence of other homologous genes or a complex regulation
      operating on a single gene. Here we report evidence for the latter, as we find
      that AKNA is encoded by a single gene that spans a 61-kb locus of 24 exons on the
      fragile FRA9E region of human chromosome 9q32. This gene gives rise to at least
      nine distinct transcripts, most of which are expressed in a tissue-specific
      manner in lymphoid organs. Many of the AKNA transcripts originate from
      alternative splicing; others appear to derive from differential polyadenylation
      and promoter usage. The alternative AKNA transcripts are predicted to encode
      overlapping protein isoforms, some of which (p70 and p100) are readily detectable
      using a polyclonal anti-AKNA antisera that we generated. We also find that AKNA
      PEST-dependent cleavage into p50 polypeptides is targeted to mature B cells and
      appears to be required for CD40 upregulation. The unusual capacity of the AKNA
      gene to generate multiple transcripts and proteins may reflect its functional
      diversity, and it may also provide a fail-safe mechanism that preserves AKNA
      expression.

PMID- 15869417
TI  - In vivo generation of cartilage from periosteum.
AB  - Periosteum has chondrogenic and osteogenic potential and plays an important role
      in fracture healing. The purpose of this study was to evaluate the reactive
      tissue formed after damaging the periosteum. Damaging the periosteum may be a way
      to generate ectopic cartilage or bone, which may be useful for the repair of
      articular cartilage and bone defects. Periosteum was bilaterally dissected from
      the proximal medial tibia of New Zealand White rabbits. Reactive periosteal
      tissue was harvested 10, 20, and 40 days postsurgery and analyzed for expression
      of collagen types I, II, and X, aggrecan, osteopontin, and osteonectin (by
      reverse transcription-polymerase chain reaction) and collagen types I and II (by
      immunohistochemistry). Reactive tissue was present in 93% of cases.
      Histologically, this tissue consisted of hyaline cartilage at follow-up days 10
      and 20. Expression of collagen type II and aggrecan was present at 10 and 20 days
      postsurgery. Highest expression was at 10 days. Expression of collagen type X
      increased up to 20 days. No significant changes in the mRNA expression of
      osteopontin or osteonectin were observed. Immunohistochemistry confirmed the
      presence of cartilage, which was positive for collagen types I and II at 10 days
      and only for collagen type II at 20 days. At 20 days postsurgery the onset of
      bone formation was also observed. At 40 days postsurgery, the reactive tissue had
      almost completely turned into bone. The quality and amount of cartilage formed 10
      days postsurgery make this technique potentially useful to fill large cartilage
      and bone defects. Also, periosteal callus formation, providing possible useful
      information for tissue engineering techniques, can be studied with this model.

PMID- 15869416
TI  - Differentiation ability of rat postnatal dental pulp cells in vitro.
AB  - The current rapid progression in stem cell research has enhanced our knowledge of
      dental tissue regeneration. In this study, rat dental pulp cells were isolated
      and their differentiation ability was evaluated. First, dental pulp cells were
      obtained from maxillary incisors of male Wistar rats. Immunochemistry by stem
      cell marker STRO-1 proved the existence of stem cells or progenitors in the
      isolated cell population. The dissociated cells were then cultured both on smooth
      surfaces and on three-dimensional (3-D) scaffold materials in medium supplemented
      with beta-glycerophosphate, dexamethasone, and L-ascorbic acid. Cultures were
      analyzed by light and scanning electron microscopy and, on proliferation,
      alkaline phosphatase activity and calcium content were determined and the
      polymerase chain reaction was performed for dentin sialophosphoprotein,
      osteocalcin, and collagen type I. These cells showed the ability to differentiate
      into odontoblast-like cells and produced calcified nodules, which had components
      similar to dentin. In addition, we found that the "odontogenic" properties of the
      isolated cells were supported by three-dimensional calcium phosphate and titanium
      scaffolds equally well.

PMID- 15869418
TI  - Molecular biological evaluation of bioactive glass microspheres and adjunct bone
      morphogenetic protein 2 gene transfer in the enhancement of new bone formation.
AB  - Bioactive glass is a promising osteoconductive silica-based biomaterial for
      guidance of new bone growth. On the basis of several in vitro studies, the
      material appears able to promote osteoblast functions. In our in vivo study, the
      osteopromotive effect of bioactive glass microspheres seemed to surpass the
      osteoinductive action of direct adenovirus-mediated human bone morphogenetic
      protein 2 (BMP-2) gene transfer in a noncritical size bone defect model. The
      current study was initiated to elucidate the molecular mechanism behind bioactive
      glass action with or without adjunct BMP-2 gene transfer. A standardized bone
      defect of the rat tibia was filled with bioactive glass microspheres and injected
      with adenovirus carrying the human BMP-2 gene (RAdBMP-2). Control defects were
      left empty or filled with bioactive glass microspheres with injection of
      adenovirus carrying the lacZ reporter gene or saline. Quantitative polymerase
      chain reaction confirmed the expression of the transferred human BMP-2 gene at
      the defect area at 4 days, but not in intact reference tissues. Bone matrix
      components (collagens I, II, and III, osteocalcin, osteonectin, and osteopontin)
      and resorption markers (cathepsin K and MMP-9), determined by Northern analysis,
      showed a completely different pattern of gene expression in defects filled with
      bioactive glass compared with control defects left to heal without filling.
      Bioactive glass induced a long-lasting production of bone matrix with concurrent
      upregulation of osteoclastic markers, a sign of high bone turnover. Combining
      RAdBMP-2 gene transfer with bioactive glass decelerated the high turnover, but
      did not influence the balance of synthesis and resorption. This molecular
      analysis confirmed not only the highly osteopromotive effect of bioactive glass
      microspheres, but also the accelerated rate of new bone resorption on its
      surface. At least in noncritical size defects this impact of bioactive glass
      seems to saturate new bone formation on its surface and thereby overshadow the
      effect of BMP-2 gene transfer.

PMID- 15869420
TI  - Dexamethasone effects on rat hepatocyte spheroid formation and function.
AB  - Hepatocytes cultured on moderately adhesive surfaces or in spinner flasks
      spontaneously self-assemble into spherical tissue-like aggregates (spheroids).
      These spheroids have smooth surfaces and tissue-like polarized cell morphology,
      including bile canalicular-like channels, and maintain high viability and liver
      specific functions for extended culture periods. Dexamethasone (DEX), a synthetic
      glucocorticoid, is known to elicit various responses in gene expression, and is
      often added to hepatocyte culture medium. The morphology and liver-specific
      protein production of hepatocyte spheroids were assessed under DEX concentrations
      ranging from 50 nM to 10 microM. DEX altered the kinetics of spheroid formation
      in a concentration-dependent fashion, with increasing concentrations inhibiting
      aggregation and promoting aggregate disassembly on culture dishes. DEX addition
      to spinner cultures resulted in smaller, more irregularly shaped spheroids and a
      higher incidence of aggregate clumping. Albumin and urea production were also
      higher in DEX cultures, but this effect was not as sensitive to concentration and
      occurred irrespective of the state of aggregation. RTPCR was utilized to assess
      the mRNA levels of extracellular matrix proteins, E-cadherin, and cytochrome P
      450 enzymes. Results indicated a slight increase in fibronectin and collagen III
      mRNA early in the cultures, possibly contributing to the changes in morphology
      observed.

PMID- 15869421
TI  - Sustaining a bioartificial liver under hypothermic conditions.
AB  - Bioartificial liver (BAL) devices employing xenogeneic hepatocytes are being
      developed as a temporary support of liver failure. For clinical applications,
      transporting such a device from the manufacturing site to the hospital is
      necessary. We investigated the effect of hypothermic treatment on the performance
      of the collagen-entrapment BAL device developed at the University of Minnesota. A
      number of chemical protectants were examined for their effectiveness in
      minimizing damage to hepatocytes. Preincubation with protectant
      (tauroursodeoxycholic acid, TUDCA) before hypothermic treatment improved
      posttreatment BAL performance. Oxygen consumption and albumin and urea synthesis
      all resumed at levels comparable to pretreatment levels. The method described
      will facilitate the application of BAL in the treatment of liver failure.

PMID- 15869419
TI  - Noninvasive measurement of viable cell number in tissue-engineered constructs in
      vitro, using 1H nuclear magnetic resonance spectroscopy.
AB  - Noninvasive monitoring of tissue-engineered constructs is of critical importance
      for accurate characterization of constructs and their remodeling in vitro and in
      vivo. This study investigated the utility of (1)H NMR spectroscopy to
      noninvasively quantify viable cell number in tissue-engineered substitutes in
      vitro. Agarose disk-shaped constructs containing betaTC3 cells were employed as
      the model tissue-engineered system. Two construct prototypes containing different
      initial cell numbers were monitored by localized, water-suppressed 1H NMR
      spectroscopy over the course of 13 days. (1)H NMR measurements of the total
      choline resonance at 3.2 ppm were compared with results from the traditional cell
      viability assay MTT and with insulin secretion rates. Results show a strong
      linear correlation between total choline and MTT (R (2) = 0.86), and between
      total choline and insulin secretion rate (R (2) = 0.90). Overall, this study
      found noninvasive measurement of total choline to be an accurate and
      nondestructive assay for monitoring viable betaTC3 cell numbers in tissue
      engineered constructs. The applicability of this method to in vivo monitoring is
      also discussed.

PMID- 15869422
TI  - Poly(lactic-co-glycolic acid) microspheres as an injectable scaffold for
      cartilage tissue engineering.
AB  - Injectable scaffold has raised great interest for tissue regeneration in vivo,
      because it allows easy filling of irregularly shaped defects and the implantation
      of cells through minimally invasive surgical procedures. In this study, we
      evaluated poly(lactic-co-glycolic acid) (PLGA) microsphere as an injectable
      scaffold for in vivo cartilage tissue engineering. PLGA microspheres (30-80
      microm in diameter) were injectable through various gauges of needles, as the
      microspheres did not obstruct the needles and microsphere size exclusion was not
      observed at injection. The culture of chondrocytes on PLGA microspheres in vitro
      showed that the microspheres were permissive for chondrocyte adhesion to the
      microsphere surface. Rabbit chondrocytes were mixed with PLGA microspheres and
      injected immediately into athymic mouse subcutaneous sites. Chondrocyte
      transplantation without PLGA microspheres and PLGA microsphere implantation
      without chondrocytes served as controls. Four and 9 weeks after implantation,
      chondrocytes implanted with PLGA microspheres formed solid, white cartilaginous
      tissues, whereas no gross evidence of cartilage tissue formation was noted in the
      control groups. Histological analysis of the implants by hematoxylin and eosin
      staining showed mature and well-formed cartilage. Alcian blue/safranin O staining
      and Masson's trichrome staining indicated the presence of highly sulfated
      glycosaminoglycans and collagen, respectively, both of which are the major
      extracellular matrices of cartilage. Immunohistochemical analysis showed that the
      collagen was mainly type II, the major collagen type in cartilage. This study
      demonstrates the feasibility of using PLGA microspheres as an injectable scaffold
      for in vivo cartilage tissue engineering. This scaffold may be useful to
      regenerate cartilaginous tissues through minimally invasive surgical procedures
      in orthopedic, maxillofacial, and urologic applications.

PMID- 15869423
TI  - Effects of cell-to-collagen ratio in mesenchymal stem cell-seeded implants on
      tendon repair biomechanics and histology.
AB  - Autogenous tissue-engineered constructs were fabricated at four cell-to-collagen
      ratios (0.08, 0.04, 0.8, and 0.4 M/mg) by seeding mesenchymal stem cells (MSCs)
      from 16 adult rabbits at one of two seeding densities (0.1 x 10(6) and 1 x 10(6)
      cells/mL) in one of two collagen concentrations (1.3 and 2.6 mg/mL). The highest
      two ratios (0.4 and 0.8 M/mg) were damaged by excessive cell contraction and
      could not be used in subsequent in vivo studies. The remaining two sets of
      constructs were implanted into bilateral full-thickness, full-length defects
      created in the central third of the patellar tendon (PT). At 12 weeks after
      surgery, repair tissues were assigned for biomechanical (n = 13) and histological
      (n = 3) analyses. A second group of rabbits (n = 6) received bilateral acellular
      implants with the same two collagen concentrations. At 12 weeks, repair tissues
      were also assigned for biomechanical (n = 4) and histological (n = 2) analyses.
      No significant differences were observed in any structural or material properties
      or in histological appearance among the two cell-seeded and two acellular repair
      groups. Average maximum force and maximum stress of the repairs were
      approximately 30% of corresponding values for the central one-third of normal PT
      and higher than peak in vivo forces measured in rabbit PT from one of our
      previous publications. However, average repair stiffness and modulus were only 30
      and 20% of normal PT values, respectively. Current repairs achieved higher
      maximum forces than in previous studies and without ectopic bone, but will need
      to achieve sufficient stiffness as well to be effective in the in vivo range of
      loading.

PMID- 15869424
TI  - Adipose tissue model using three-dimensional cultivation of preadipocytes seeded
      onto fibrous polymer scaffolds.
AB  - A better understanding of the mechanism of adipose tissue differentiation is of
      paramount importance in the development of therapeutic strategies for the
      treatment and prevention of obesity and type 2 diabetes mellitus. Optimal results
      using tissue culture models can be expected only when the in vitro adipocyte
      resembles adipose tissue in vivo as closely as possible. In this study, we used
      tissue-engineering principles to develop a three-dimensional (3-D) culture system
      to mimic the geometry of adipose tissue in vivo. Mouse preadipocyte 3T3-L1 cells
      were seeded onto nonbiodegradable fibrous polyethylene terephthalate scaffolds
      and differentiated with a hormone cocktail consisting of insulin, dexamethasone,
      isobutylmethylxanthine, and fetal calf serum. Cell morphology, growth,
      differentiation, and function were studied by immunocytochemistry, reverse
      transcriptase-polymerase chain reaction (RT-PCR), Western blotting, enzyme-linked
      immunosorbent assay, and oil red O staining. Cells grown on 3-D fibrous scaffolds
      were differentiated in situ by hormone induction with high efficiency
      (approximately 90%) as shown by scanning electron microscopy.
      Immunocytochemistry, immunoblot analysis, and RT-PCR revealed that the 3-D
      constructs expressed adipocyte-specific genes, including peroxisome proliferator
      activated receptor gamma, leptin, adipsin, aP2, adiponectin, GLUT4, and resistin.
      Adipocytes matured on 3-D constructs secreted leptin at levels even greater than
      that of fully differentiated adipocytes in 2-D conventional cell cultures.
      Finally, adipocyte-specific phenotypic function was demonstrated by accumulation
      of neutral lipids in larger fat droplets. In conclusion, preadipocytes grown on 3
      D matrices acquire morphology and biological features of mature adipocytes. This
      new culture model should have significant utility for in vitro studies of
      adipocyte cell biology and development.

PMID- 15869425
TI  - Human periodontal ligament cell sheets can regenerate periodontal ligament tissue
      in an athymic rat model.
AB  - Conventional periodontal regeneration methods remain insufficient to attain
      complete and reliable clinical regeneration of periodontal tissues. We have
      developed a new method of cell transplantation using cell sheet engineering and
      have applied it to this problem. The purpose of this study was to investigate the
      characteristics of human periodontal ligament (HPDL) cell sheets retrieved from
      culture on unique temperature-responsive culture dishes, and to examine whether
      these cell sheets can regenerate periodontal tissues. The HPDL cell sheets were
      examined histologically and biochemically, and also were transplanted into a
      mesial dehiscence model in athymic rats. HPDL cells were harvested from culture
      dishes as a contiguous cell sheet with abundant extracellular matrix and retained
      intact integrins that are susceptible to trypsin-EDTA treatment. In the animal
      study, periodontal ligament-like tissues that include an acellular cementum-like
      layer and fibrils anchoring into this layer were identified in all the athymic
      rats transplanted with HPDL cell sheets. This fibril anchoring highly resembles
      native periodontal ligament fibers; such regeneration was not observed in
      nontransplanted controls. These results suggest that this technique, based on the
      concept of cell sheet engineering, can be useful for periodontal tissue
      regeneration.

PMID- 15869426
TI  - Enhanced derivation of osteogenic cells from murine embryonic stem cells after
      treatment with ionic dissolution products of 58S bioactive sol-gel glass.
AB  - Embryonic stem (ES) cells represent a potentially useful cell source for tissue
      regeneration. Previously, using factors known to enhance differentiation and
      mineralization of primary osteoblasts, we were able to generate cell populations
      enriched with osteoblasts from a murine ES cell source. Dexamethasone was a
      potent inducer of osteoblast differentiation and the timing of stimulation
      markedly increased the proportion of osteoblast lineage cells. This study
      examined whether inorganic stimuli derived from bioactive glasses could affect
      the differentiation of osteoblasts in an ES-cell based system. Previous work has
      demonstrated the ability of soluble ions released from bioactive glasses
      undergoing dissolution in vitro to stimulate gene expression characteristic of a
      mature phenotype in primary osteoblasts. We report here on the potential of
      soluble extracts prepared from 58S sol-gel bioactive glass to further enhance
      lineage-specific differentiation in murine ES cells. Differentiation of ES cells
      into osteogenic cells was characterized by the formation of multilayered,
      mineralized nodules. These nodules contained cells expressing the transcription
      factor runx2/cbfa-1, and deposition of osteocalcin in the extracellular matrix
      was detected by immunostaining. When differentiating cells were placed in an
      osteoblast maintenance medium supplemented with soluble extracts prepared from
      bioactive glass powders, we observed increased formation of mineralized nodules
      (98 +/- 6%, mean +/- SEM) and alkaline phosphatase activity (56 +/- 14%, mean +/-
      SEM) in a pattern characteristic of osteoblast differentiation. This effect of
      the glass extracts exhibited dose dependency, with alkaline phosphatase activity
      and nodule formation increasing with extract concentrations. Compared with medium
      supplemented with dexamethasone, which had previously been used to enhance
      osteoblast lineage derivation, the glass extracts were as effective at inducing
      formation of mineralized nodules by murine ES cells. When glass extracts were
      used in combination with dexamethasone, a further increase in the number of
      nodules was observed (110 +/- 16%; cf. 83 +/- 7% for dexamethasone alone). This
      study demonstrates the capacity of an entirely inorganic material to stimulate
      differentiation of ES cells toward a lineage with therapeutic potential in tissue
      engineering applications.

PMID- 15869427
TI  - Construction and delivery of tissue-engineered human retinal pigment epithelial
      cell sheets, using magnetite nanoparticles and magnetic force.
AB  - Choroidal neovascularization (CNV) is the most severe form of age-related macular
      degeneration (AMD), which causes rapid visual loss. Transplantation of cultured
      retinal pigment epithelium (RPE) cell sheet by tissue engineering is a possible
      approach to the treatment of CNV. In the present study, we investigated the
      possibility of using magnetite nanoparticles and magnetic force to construct and
      deliver RPE cell sheets in vitro. When magnetite cationic liposomes (MCLs),
      having a positive charge at the surface, were added to ARPE-19 human RPE cells at
      a concentration of 25 or 50 pg of magnetite per cell, the cells took up 40 to 55%
      of the MCLs. The magnetically labeled ARPE-19 cells (8 x 10(3) cells/mm(2), which
      corresponds to 10-fold the confluent concentration against the culture area [4
      mm(2)]) were seeded into an ultra-low-attachment plate and a magnet (4000 G) was
      placed under the well. The magnetically labeled ARPE-19 cells formed an
      approximately 15-layered cell sheet after a 24 h of culture. When the magnet was
      removed, the sheets were detached from the bottom of the plate and then harvested
      and transferred to a tissue culture dish, using a magnet. Subsequently, the cell
      sheets were attached onto the dish, and the cells growing on the sheets were
      observed. This novel methodology, termed "magnetic force-based tissue
      engineering" (Mag-TE), is a possible approach for CNV treatment.

PMID- 15869428
TI  - Use of embryonic stem cell-derived endothelial cells as a cell source to generate
      vessel structures in vitro.
AB  - Embryonic stem (ES) cells could potentially serve as an excellent cell source for
      various applications in regenerative medicine and tissue engineering. Our
      laboratory is particularly interested in generating a reproducible endothelial
      cell source for the development of prevascularized materials for tissue/organ
      reconstruction. After developing methods to isolate highly purified (>96%)
      proliferating populations of endothelial cells from mouse embryonic stem cells,
      we tested their ability to form three-dimensional (3-D) vascular structures in
      vitro. The ES cell-derived endothelial cells were embedded in 3-D collagen gel
      constructs with rat tail collagen type I (2 mg/mL) at a concentration of 10(6)
      cells/mL of gel. The gels were observed daily with a phase-contrast microscope to
      analyze the time course for endothelial cell assembly. The first vessels were
      observed between days 3 and 5 after gel construct formation. The number and
      complexity of structures steadily increased, reaching a maximum before beginning
      to regress. By 2 weeks, all vessel-like structures had regressed back to single
      cells. Histology and fluorescent images of the vessel-like structures verified
      that tube structures were multicellular and could develop patent lumens. We have
      shown that endothelial cells derived, purified and expanded in vitro from ES
      cells sustain an important endothelial cell function, the ability to undergo
      vasculogenesis in collagen gels, indicating that endothelial products derived in
      vitro from stem cells could be useful in regenerative medicine applications.

PMID- 15869429
TI  - Neurotrophin-induced differentiation of human embryonic stem cells on three
      dimensional polymeric scaffolds.
AB  - Human embryonic stem (hES) cells have the potential to form various cell types,
      including neural cells for the treatment of diseases such as Parkinson's, spinal
      cord injury, and glaucoma. Here, we have investigated the neuronal
      differentiation of hES cells on three-dimensional scaffolds fabricated from
      degradable poly(alpha-hydroxy esters) including poly(lactic-co-glycolic acid) and
      poly(L-lactic acid). When cultured in vitro, neural rosette-like structures
      developed throughout the scaffolds with differentiation dependent on factors in
      the medium (e.g., retinoic acid [RA], nerve growth factor [NGF], and neurotrophin
      3 [NT-3]) and the differentiation stage of the cells. Specifically, enhanced
      numbers of neural structures and staining of nestin (a marker of neural
      precursors) and beta(III)-tubulin (indicative of neural differentiation) were
      observed with hES cell-seeded polymer scaffolds when cultured with both NGF and
      NT-3 when compared with control medium. In addition, vascular structures were
      found throughout the engineered tissues when cultured with the neurotrophins, but
      not in the presence of RA.

PMID- 15869430
TI  - Hyaluronic acid-poly-D-lysine-based three-dimensional hydrogel for traumatic
      brain injury.
AB  - Brain tissue engineering in the postinjury brain represents a promising option
      for cellular replacement and rescue, providing a cell scaffold for either
      transplanted or resident cells. In this article, a hyaluronic acid (HA)-poly-D
      lysine (PDL) copolymer hydrogel with an open porous structure and viscoelastic
      properties similar to neural tissue has been developed for brain tissue
      engineering. The chemicophysical properties of the hydrogel with HA:PDL ratios of
      10:1, 5:1, and 4:1 were investigated by scanning electron microscopy (SEM) and X
      ray photoelectron spectrometry. Neural cells cultured in the hydrogel were
      studied by phase-contrast microscope and SEM. The incorporation of PDL peptides
      into the HA-PDL hydrogel allowed for the modulation of neuronal cell adhesion and
      neural network formation. Macrophages and multinucleated foreign body giant cells
      found at the site of implantation of the hydrogel in the rat brain within the
      first weeks postimplantation decreased in numbers after 6 weeks, consistent with
      the host response to inert implants in numerous tissues. Of importance was the
      infiltration of the hydrogel by glial fibrillary acidic protein-positive cells
      reactive astrocytes-by immunohistochemistry and the contiguity between the
      hydrogel and the surrounding tissue demonstrated by SEM. These findings indicated
      the compatibility of this hydrogel with brain tissue. Collectively, the results
      demonstrate the promise of an HA-PDL hydrogel as a scaffold material for the
      repair of defects in the brain.

PMID- 15869431
TI  - Proliferation and phenotypic preservation of rat parotid acinar cells.
AB  - The purpose of this study is to develop an initial step in salivary gland tissue
      engineering through proliferation and phenotypic preservation of rat parotid
      acinar cells in vitro. By using the explant outgrowth technique and M199 medium
      with the addition of sialic acid, acinar cells not only survived for more than 30
      days in the absence of basement membrane substrates but also proliferated to
      yield cells with acinar phenotypic expression. Furthermore, we tested whether
      chitosan can be used as a synthetic extracellular matrix to culture salivary
      acinar cells. Chitosan is a deacetylated product of chitin, which is a plentiful
      polysaccharide found in nature and is safe for the human body, but little is
      known about the utility of chitosan in culturing salivary acinar cells. It was
      found that coating fibronectin on chitosan membrane improved the attachment of
      acinar cells in the initial stage. However, the poor attachment of acinar cells
      on pure chitosan membrane did not affect cell growth after longer culture times,
      indicating that chitosan is potentially useful as a tissue-engineering scaffold
      of the salivary gland. These in vitro results are encouraging because such a
      culture system may serve as an artificial salivary gland for future use in the
      treatment of patients with salivary hypofunction.

PMID- 15869432
TI  - Bioreactor design for successive culture of anchorage-dependent cells operated in
      an automated manner.
AB  - A novel bioreactor system was designed to perform a series of batchwise cultures
      of anchorage-dependent cells by means of automated operations of medium change
      and passage for cell transfer. The experimental data on contamination frequency
      ensured the biological cleanliness in the bioreactor system, which facilitated
      the operations in a closed environment, as compared with that in flask culture
      system with manual handlings. In addition, the tools for growth prediction (based
      on growth kinetics) and real-time growth monitoring by measurement of medium
      components (based on small-volume analyzing machinery) were installed into the
      bioreactor system to schedule the operations of medium change and passage and to
      confirm that culture proceeds as scheduled, respectively. The successive culture
      of anchorage-dependent cells was conducted with the bioreactor running in an
      automated way. The automated bioreactor gave a successful culture performance
      with fair accordance to preset scheduling based on the information in the latest
      subculture, realizing 79- fold cell expansion for 169 h. In addition, the
      correlation factor between experimental data and scheduled values through the
      bioreactor performance was 0.998. It was concluded that the proposed bioreactor
      with the integration of the prediction and monitoring tools could offer a
      feasible system for the manufacturing process of cultured tissue products.

PMID- 15869433
TI  - Sustained in vivo gene delivery from agarose hydrogel prolongs nonviral gene
      expression in skin.
AB  - Prolonging gene expression in skin using safe, nonviral gene delivery techniques
      could impact skin regeneration and wound healing, decrease infection, and
      potentially improve the success of tissue-engineered skin. To this end, an
      injectable, agarose-based delivery system was tested and shown to prolong
      nonviral gene expression in the skin. DNA was compacted with polylysine to
      improve DNA stability in the presence of nucleases. Up to 25 microg of compacted
      luciferase plasmid with or without agarose hydrogel was injected intradermally in
      rodents. Bioluminescence imaging was used for longitudinal, noninvasive
      monitoring of gene expression in vivo for 35 days. Injections of DNA in solution
      produced gene expression for only 5-7 days, whereas the sustained release of
      compacted DNA from the agarose system prolonged expression, with more than 500 pg
      (20% of day 1 levels) of luciferase per site for at least 35 days. Southern
      blotting confirmed that the agarose system extended DNA retention, with
      significant plasmid present through day 7, as compared with DNA in solution,
      which had detectable DNA only on day 1. Histology revealed that agarose invoked a
      wound-healing response through day 14. Tissue-engineering and wound-healing
      applications may benefit from the agarose gene delivery system.

PMID- 15869434
TI  - Engineered adipose tissue from human mesenchymal stem cells maintains predefined
      shape and dimension: implications in soft tissue augmentation and reconstruction.
AB  - Soft tissue augmentation is a widespread practice in plastic and reconstructive
      surgery. The objective of the present study was to engineer adipose tissue
      constructs with predefined shape and dimensions, potentially utilizable in soft
      tissue augmentation and reconstruction, by encapsulating adult stem cell-derived
      adipogenic cells in a biocompatible hydrogel system. Bone marrow-derived adult
      human mesenchymal stem cells (hMSCs) were preconditioned by 1 week of exposure to
      adipogenic- inducing supplement followed by photoencapsulation in poly(ethylene
      glycol) diacrylate (PEGDA) hydrogel in predefined shape and dimensions. In two
      parallel experiments, the resulting hMSC-derived adipogenic cell-polymer
      constructs were either incubated in vitro in adipogenic medium or implanted in
      vivo in the dorsum of immunodeficient mice for 4 weeks. Tissue-engineered
      adipogenic constructs demonstrated positive reaction to oil red O staining both
      in vitro and in vivo, and expressed PPAR-gamma2 adipogenic gene marker in vivo.
      By contrast, control PEGDA hydrogel constructs encapsulating undifferentiated
      hMSCs failed to demonstrate the adipogenic gene marker and were negative for oil
      red O staining. Recovered in vitro and in vivo constructs maintained their
      predefined physical shape and dimensions. These data demonstrate that adipose
      tissue engineered from human mesenchymal stem cells can retain predefined shape
      and dimensions for soft tissue augmentation and reconstruction.

PMID- 15869435
TI  - Therapeutic neovascularization: contributions from bioengineering.
AB  - A number of pathological entities and surgical interventions could benefit from
      therapeutic stimulation of new blood vessel formation. Although strategies
      designed for promoting neovascularization have shown promise in preclinical
      models, translation to human application has met with limited success when
      angiogenesis is used as the single therapeutic mechanism. While clinical
      protocols continue to be optimized, a number of exciting new approaches are being
      developed. Bioengineering has played an important role in the progress of many of
      these innovative new strategies. In this review, we present a general outline of
      therapeutic neovascularization, with an emphasis on investigations using
      engineering principles to address this vexing clinical problem. In addition, we
      identify some limitations and suggest areas for future research.

PMID- 15869436
TI  - Subculture of chondrocytes on a collagen type I-coated substrate with suppressed
      cellular dedifferentiation.
AB  - To evaluate the degree of cellular dedifferentiation, subculture of chondrocytes
      was conducted on a surface coated with collagen type I at a density of 1.05
      mg/cm(2). In the primary culture, most of the cells were round in shape on the
      collagen (CL) substrate, whereas fibroblastic and partially extended cells were
      dominant on the polystyrene plastic (PS) substrate. Stereoscopic observation
      revealed that the round-shaped cells on the CL substrate were hemispherical with
      nebulous and punctuated F-actin filaments, whereas the fibroblastic cells on the
      PS substrate were flattened with fully developed stress fibers. This suggested
      that cell polarization was suppressed during culture on the former substrate.
      Although serial passages of chondrocytes through subcultures on the CL and PS
      substrates caused a decrease in the number of round-shaped cells, the
      morphological change was appreciably suppressed on the CL substrate, as compared
      with that on the PS substrate. It was found that only round-shaped cells formed
      collagen type II, which supports the view that cellular dedifferentiation can be
      suppressed to some extent on the CL substrate. Three-dimensional cultures in
      collagen gel were performed with cells isolated freshly and passaged on the CL or
      PS substrate. Cell density at 21 days in the culture of cells passaged on the CL
      substrate was comparable to that in the culture of freshly isolated cells, in
      spite of a significant reduction in cell density observed in the culture of cells
      passaged on the PS substrate. In addition, histological analysis revealed that
      the expression of glycosaminoglycans and collagen type II was of significance in
      the collagen gel with cells passaged on the CL substrate, and likewise in the gel
      with freshly isolated cells. This indicated that the CL substrate could offer a
      monolayer culture system for expanding chondrocyte cells.

PMID- 15869437
TI  - In vitro bone formation induced by immunosuppressive agent tacrolimus hydrate
      (FK506).
AB  - When rat bone marrow cells were cultured with an immunosuppressive agent,
      tacrolimus hydrate (FK506), as well as with beta-glycerophosphate and vitamin C,
      numerous cell clusters became positive for alkaline phosphatase activity.
      Scanning electron microscopy revealed mineralized bone matrix in the cell
      clusters, which was identical to that of living bone. High levels of alkaline
      phosphatase (ALP), indicating osteoblastic activity, and high levels of
      osteocalcin (Oc) and calcium were found in the mature bone matrix of the
      cultures. There was significantly increased expression of mRNAs for ALP and Oc.
      These results indicate that the cultures contained both bone matrix and high
      osteoblastic activity, suggesting that FK506 induces ossification.

PMID- 15869438
TI  - Mesothelial cell sheets cultured on fibrin gel prevent adhesion formation in an
      intestinal hernia model.
AB  - In the present study, we examined a novel technique to prevent adhesion formation
      in a rat intestinal hernia model with mesothelial cell sheets cultured on fibrin
      gel. Mesothelial cells were obtained from isologous rats by enzymatic
      disaggregation of mesentery and cultured on fibrin gel. Electron microscopy
      revealed that these cultured cells form contiguous monolayer cell sheets with
      well-developed microvilli. These tissue-engineered constructs were grafted in
      vivo to an intestinal hernia model that results in regular surgical adhesions
      without treatment. Five days postgrafting, rats were sacrificed. Adhesion
      formation was not observed in rats grafted with the constructs, whereas severe
      adhesions were observed in all control rats. Constructs seeded with mesothelial
      cells isolated from EGFP-transgenic rats clearly revealed that grafted
      mesothelial cells remained at the host tissue site even after fibrin scaffold
      degradation. These cells developed more abundant microvilli in vivo than those in
      vitro. These results show that cultured mesothelial cell sheets are effective in
      preventing adhesion formation and should reduce postoperative complications
      caused by adhesion formation.

PMID- 15869439
TI  - Hepatic organoid formation in collagen sponge of cells isolated from human liver
      tissues.
AB  - We examined whether small hepatocytes (SHs), which are hepatic progenitor cells,
      could be isolated from a normal human liver and whether human hepatic cells could
      form hepatic organoids in a collagen sponge. Normal liver tissues were obtained
      from resected specimens from nine patients who underwent hepatic resection.
      Isolated hepatic cells were plated on dishes and a collagen sponge. More than 1
      month later, SH-like cells appeared and proliferated on the dishes, whereas cell
      aggregates were formed in the sponge and showed characteristic tissue
      architecture: columnar and/or cuboidal epithelial cells lined the surface of the
      sponge. Clusters of epithelial cells with a large cytoplasm and ductular
      structures were observed under the lining cells. The lining and ductular cells
      were positive for cytokeratins 7 and 19, which indicated they were biliary
      epithelial cells (BECs), and the epithelial cells forming clusters were positive
      for the anti-human hepatocyte antibody, identifying them as hepatocytes. Some
      lining cells were positive for both the hepatic marker and the BEC markers. The
      cells in the collagen sponge actively proliferated and the hepatocytes excreted
      albumin into the medium. Thus, hepatic organoids could be reconstructed in a
      collagen sponge by normal human liver cells.

PMID- 15869440
TI  - Bone marrow cells from normal and ovariectomized rats respond differently to
      basic fibroblast growth factor and bone morphogenetic protein 2 treatment in
      vitro.
AB  - The protein growth factors basic fibroblast growth factor (bFGF) and bone
      morphogenetic protein 2 (BMP-2) are being actively pursued for bone tissue
      engineering. Although both proteins are capable of stimulating osteogenic
      activity of bone marrow cells (BMCs), no studies have addressed the effect of
      estrogen deficiency on the growth factor responsiveness of BMCs. This study
      investigated the osteogenic response of BMCs from normal and ovariectomized (OVX)
      rats to bFGF and BMP- 2. In the absence of growth factors, a higher number of
      total colony-forming units (t-CFU) and alkaline phosphatase-expressing CFU (ALP
      CFU) were obtained with BMCs derived from OVX rats. The percentage of ALP-CFU,
      however, was not significantly different between BMCs from the two groups of
      rats. Whereas BMP-2 did not influence the t-CFU and percentage of ALP-CFU, bFGF
      decreased t-CFU in BMCs derived from OVX rats and reduced the percentage of ALP
      CFU in BMCs from both types of rats. Consistent with the higher t-CFU, the number
      of mineralized colonies (min-CFU) was also higher for BMCs derived from OVX rats.
      The number of min-CFU was not influenced by BMP-2 treatment, but was reduced with
      bFGF treatment. Comparison of the growth factor effects on a per-cell (DNA) basis
      confirmed the expected stimulatory effect of BMP-2 on ALP activity and
      mineralization in BMCs from normal rats, but these two parameters were not
      unequivocally stimulated in BMCs from OVX rats. We conclude that BMCs derived
      from normal and OVX rats exhibited significant differences in their osteogenic
      response to bFGF and BMP-2 treatment.

PMID- 15869441
TI  - Bone morphogenetic protein 2 and retinoic acid accelerate in vivo bone formation,
      osteoclast recruitment, and bone turnover.
AB  - Reconstruction of craniofacial defects presents a substantial biomedical burden,
      and requires complex surgery. Interestingly, children after age 2 years and
      adults are unable to heal large skull defects. This nonhealing paradigm provides
      an excellent model system for craniofacial skeletal tissueengineering strategies.
      Previous studies have documented the in vivo osteogenic potential of adipose
      derived stromal (ADS) cells and bone marrow-derived stromal (BMS) cells. This
      study investigates the ability to accelerate in vivo osteogenesis on ex vivo
      recombinant human bone morphogenetic protein 2 (BMP-2) and retinoic acid
      stimulation. Mouse osteoblasts, ADS cells, and BMS cells were seeded onto apatite
      coated PLGA scaffolds, stimulated with rhBMP-2 and retinoic acid ex vivo for 4
      weeks, and subsequently implanted into critically sized (4 mm) calvarial defects.
      Samples were harvested after 2, 4, 8, and 12 weeks. Areas of complete bony
      bridging were noted as early as 2 weeks in vivo; however, osteoclasts were
      attracted to the scaffold as identified by calcitonin receptor staining and
      tartrate-resistant acid phosphatase activity staining. Although the optimal
      method of in vitro osteogenic priming for mesenchymal cells remains unknown,
      these results provide evidence that BMP-2 and retinoic acid stimulation of
      multipotent cells ex vivo can subsequently induce significant quantities of bone
      formation within a short time period in vivo.

PMID- 15869444
TI  - Clinically useful marrow dosimetry for targeted radionuclide therapy.

PMID- 15869445
TI  - Host immunity ignored in clinical oncology: a medical opinion.

PMID- 15869446
TI  - Establishing a clinically meaningful predictive model of hematologic toxicity in
      nonmyeloablative targeted radiotherapy: practical aspects and limitations of red
      marrow dosimetry.
AB  - In either heavily pretreated or previously untreated patient populations,
      dosimetry holds the promise of playing an integral role in the physician's
      ability to adjust therapeutic activity prescriptions to limit excessive
      hematologic toxicity in individual patients. However, red marrow absorbed doses
      have not been highly predictive of hematopoietic toxicity. Although the accuracy
      of red marrow dose estimates is expected to improve as more patient-specific
      models are implemented, these model-calculated absorbed doses more than likely
      will have to be adjusted by parameters that adequately characterize bone marrow
      tolerance in the heavily pretreated patients most likely to receive
      nonmyeloablative radiolabeled antibody therapy. Models need to be established
      that consider not only absorbed dose but also parameters that are indicative of
      pretherapy bone marrow reserve and radiosensitivity so that a clinically
      meaningful predictive model of hematologic toxicity can be established.

PMID- 15869447
TI  - Calcium phosphate nanoparticles as a novel nonviral vector for efficient
      transfection of DNA in cancer gene therapy.
AB  - To explore an efficient gene vector in cancer gene therapy, a novel nonviral
      vector calcium phosphate nanoparticle (CPNP) was developed. Transmission
      electromicroscopy and Zeta potential demonstrated that CPNP was 23.5-34.5 nm
      diameters and had +16.8 mV positive surface charges. The analysis of the CPNPDNA
      complex showed CPNP could transfer foreign DNA into targeted cells with high
      transfection efficiency, as well as its DNA-binding property and protection of
      DNA from degradation. Furthermore, the CPNP-DNA complex had no obvious
      cytotoxicity for CNE-2 cells, while the liposome-DNA complex had certain
      cytotoxicity. When the CPNP combined with suicide genes yCDglyTK for
      nasopharyngeal carcinoma (NPC) therapy in vitro, just 24.76% of cells survived
      when the wild-type CNE-2 cells were treated with the CPNP-yCDglyTK complex plus
      the prodrug, 5-FC (200 mg/mL). Otherwise, the expression of yCDglyTK was detected
      in implanted CNE-2 tumors by reverse transcription-polymerase chain reaction (RT
      PCR) analysis when the CNE-2 tumor was treated with an intratumoral injection of
      the CPNPyCDglyTK complex. Our results showed that the CPNP might be a potential
      vector for gene therapy.

PMID- 15869448
TI  - Correlation between development of pulmonary edema and response of pulmonary
      metastases of metastatic melanoma and kidney cancer to high-dose continuous
      infusion interleukin-2.
AB  - The administration of high-dose continuous intravenous infusion interleukin-2 (IL
      2) is able to induce the presence of lymphokine-activated killer (LAK) cells. LAK
      are able to nonspecifically lyse tumor cells. They are also able to lyse
      endothelial cells, which accounts for, at least in part, the capillary leak
      syndrome seen as one of the toxicities with this therapy. A pulmonary
      manifestation of capillary leak syndrome is the presence of pulmonary edema. We
      postulated that capillary leak may also be a mechanism by which LAK could
      conceivably reach pulmonary metastases or could be a reflection of damage of
      endothelial cells in vasculature supplying metastases and that capillary leak
      syndrome may actually correlate with the response of pulmonary metastases. We
      examined our database of patients with lung metastases treated with high-dose
      continuous infusion IL-2 (18 MIU/m(2)/day for 3 days) regimens. Eighteen patients
      had the following characteristics: melanoma (11), renal cancer (7), median age of
      67 years (range, 28-79 years), and males (15). All patients were treated by
      oncology nurses on either the stem cell transplant unit or oncology ward.
      Pulmonary edema was defined as the presence of pleural fluid on a chest X-ray,
      computed tomography (CT) scan, and/or as noted on a physical examination by at
      least 2 observers. No patients required endotracheal intubation, mechanical
      ventilation, or an intensive care unit transfer. The median number of cycles
      received was 6 (range, 1-13). All 8 responding patients (6 patients with
      melanoma, 2 patients with kidney cancer) manifested pulmonary edema during
      interleukin-2 therapy. Four patients with pulmonary edema were nonresponders. The
      presence of pulmonary edema correlated with the response to therapy (p = 0.01).
      The median duration of response of pulmonary nodules was 5 months (range, 1-16
      months). There is a correlation between the development of pulmonary edema and
      the response of pulmonary metastases in patients with melanoma and kidney cancer
      treated with high-dose continuous infusion interleukin-2.

PMID- 15869449
TI  - Therapeutic effects of Lycium barbarum polysaccharide (LBP) on irradiation or
      chemotherapy-induced myelosuppressive mice.
AB  - AIM: The aim of this study was to investigate the effects of Lycium barbarum
      polysaccharide (LBP) on irradiation- or chemotherapy-induced myelosuppressive
      mice and cultured peripheral blood mononuclear cells (PBMCs). METHODS: In an in
      vivo experiment, mice were irradiated with a sublethal dose of 550 cGy X-ray or
      intraperitoneally (i.p.) injected with carboplatin (CB) 125 mg/kg to produce
      severe myelosuppression. Four to 6 hours after the irradiation or injection, mice
      were subcutaneously (s.c.) injected with LBP (50, 100, and 200 mg/kg) daily from
      day 0 to day 6. Blood samples were collected from the tail veins of mice at
      different time points, and peripheral white blood cells (WBC), red blood cells
      (RBC), and platelet (PLT) counts were monitored. In an in vitro experiment, human
      PBMCs were incubated with LBP at different concentrations in combination with
      phytohemagglutinin (PHA), and the production of granulocyte colony-stimulating
      factor (G-CSF) was tested. RESULTS: Compared to the control, 50 mg/kg LBP (LBP-L)
      significantly ameliorated the decrease of peripheral WBC of irradiated
      myelosuppressive mice on day 13, and 100 mg/kg LBP (LBP-M) did the same on days
      17 and 21. All dosages of LBP significantly ameliorated the decrease of
      peripheral RBC of irradiated myelosuppressive mice on days 17 and 25. Two-hundred
      mg/kg LBP (LBP-H) and LBP-M significantly enhanced peripheral PLT counts of
      irradiated myelosuppressive mice on days 10, 13, 17, and 21, as did LBP-L on days
      13 and 17. All dosages of LBP increased peripheral WBC counts of chemotherapy
      induced myelosuppressive mice to some extent, but there was no statistic
      difference when compared to the control. LBP-H significantly ameliorated the
      decrease of peripheral RBC of chemotherapy-induced myelosuppressive mice on days
      13, 15, 17, and 20, and LBP-M and LBP-L did the same on days 15 and 17. All
      dosages of LBP significantly enhanced peripheral PLT counts of chemotherapy
      induced myelosuppressive mice on days 7 and 10, as did LBP-H on days 13, 15, and
      17, and LBP-M on days 13 and 15. Also, LBP could obviously stimulate human PBMCs
      to produce G-CSF. CONCLUSIONS: LBP promoted the peripheral blood recovery of
      irradiation or chemotherapy-induced myelosuppressive mice, and the effects may be
      the result of the stimulation of PBMCs to produce G-CSF.

PMID- 15869450
TI  - Molecular nuclear imaging: the radiopharmaceuticals (review).
AB  - Application of the nuclear approach for the detection of inherited diseases is an
      important goal for nuclear medicine and will likely result in an important
      breakthrough, which will, hopefully, lead to improved diagnoses of genetic
      defects and objective evaluations of the efficacy of therapeutic strategies.
      Although still largely in the research realm, molecular imaging is in the process
      of emerging as a vital component of the diagnosis of disease and monitoring of
      the therapy. The clinical research in nuclear medicine has made major
      advancements in the direction of molecular medicine and targeted therapy. In the
      past few years, exponential achievements have been accomplished in the
      development of molecular nuclear imaging agents, as described below.

PMID- 15869451
TI  - Studies on inducing apoptosis effects and mechanism of CIK cells for MGC-803
      gastric cancer cell lines.
AB  - The induction of apoptosis and antiproliferation effect of cytokine-induced
      killer cells (CIK cells) on MGC- 803 cells and its mechanisms were studied by
      using a tetrazolium dye-based (MTT) assay. Morphological changes were observed by
      using inverted microscope, haematoxylin/eosin (HE) staining, scanning electron
      microscope, and transmission electron microscope. The TdT-mediated dUTP nick and
      labeling (TUNEL) method was used to detect the apoptosis-induced by CIK cells.
      The expression rate of p53, p16, C-myc, Bcl-2, and Bax proteins were studied by
      using immunohistochemical staining. There were significant differences according
      to varied effector-target ratios at the same working time (p < 0.01) and the same
      effector-target ratios at different working times (p < 0.01). Inverted microscope
      and HE staining observation showed that CIK cells were closer to the target cells
      and formed a typical "rose" shape. The scanning electron microscope showed that
      most target cells had undergone apoptosis and many "apoptotic bodies," and that
      transmission electron microscopy showed condensed chromatin, disintegration of
      the nucleolus, vacuoles in the cytoplasm, and apoptotic bodies appearing in most
      target cells. TUNEL analysis showed that apoptotic cells contract and turn navy
      blue in nuclei or perinuclei in the experimental group. The apoptotic rate was
      upmodulated between 5 and 14 hours and downregulated between 14 and 24 hours in
      the "CIK" experimental group. The expression of p53, p16, C-myc, and Bcl-2 were
      significantly downregulated (p < 0.01), and the expression of Bax was upregulated
      over the time of coculture in the "CIK" experimental group, compared to the
      control group. Our studies suggested that CIK cells induce apoptosis and have an
      antiproliferative effect on human MGC-803 gastric cancer cells. The CIK cells
      kill MGC-803 gastric cancer cells by inducing apoptosis in the early stage and by
      inducing necrosis in the late stage through the downregulating expression of p53,
      C-myc, and Bcl-2 and the upregulating expression of Bax.

PMID- 15869453
TI  - Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) induces long-term durable
      responses in patients with relapsed or refractory B-Cell non-Hodgkin's lymphoma.
AB  - AIM: Yttrium-90 ((90)Y) ibritumomab tiuxetan (Zevalin) radioimmunotherapy is an
      effective treatment for relapsed or refractory B-cell non-Hodgkin's lymphoma
      (NHL), with overall response rates ranging from 74% to 82%. This retrospective
      analysis was conducted to determine the number of patients achieving long-term
      durable responses with (90)Y ibritumomab tiuxetan treatment. MATERIALS AND
      METHODS: The medical records of patients (n = 211) with relapsed, refractory, or
      transformed indolent CD20+ B-cell NHL who were treated with 90Y ibritumomab
      tiuxetan were reviewed. Time to progression (TTP) of > or =12 months was noted in
      78 patients (37%), who were identified as long-term responders and were further
      characterized. RESULTS: Median age of the long-term responders was 58 years
      (range, 24-80 years) with 44% over 60 years, and 55% were male. Notably, 59% of
      patients had received > or =2 prior regimens, 33% had received > or =3 prior
      regimens, and 37% had failed to respond to immediate prior therapy. Median
      response duration was 28.1 months (range, 10.5-80.3+ months). Median TTP was 29.3
      months (range, 12.1-81.5+ months). In patients with ongoing response, median TTP
      was 53.9 months (range, 49-82+ months). CONCLUSIONS: (90)Y ibritumomab tiuxetan
      produces durable long-term responses in patients with relapsed/refractory B-cell
      NHL. Failure to respond to prior therapy does not preclude achieving a long-term
      response with 90Y ibritumomab tiuxetan.

PMID- 15869454
TI  - The potential use of 99mTc-MDP bone scans to plan high-activity 186Re-HEDP
      targeted therapy of bony metastases from prostate cancer.
AB  - Patients with skeletal metastases from hormone-refractory prostate cancer have
      shown variable responses to high-activity therapy with (186)Re-HEDP and
      peripheral stem cell support. In this paper, we report on the use of a novel
      technique to compare sequential planar images acquired post-(186)Re-HEDP therapy
      administration with pretherapy diagnostic (99m)Tc-MDP scans, to evaluate the
      turnover of the radiopharmaceutical in normal and abnormal bone. It was found
      that the activity in normal (i.e., disease-free) segments of the spine
      demonstrates a faster effective decay than that of the metastases, with the
      latter showing only physical decay. This study showed, for the first time, a
      detailed correlation in the behavior of the (99m)Tc-MDP and (186)Re-HEDP images,
      encouraging the possibility of using the pretherapy 99mTc-MDP scan for
      estimations of absorbed doses to be delivered by prescribed activities of (186)Re
      HEDP.

PMID- 15869455
TI  - Feasibility of dosimetry-based high-dose 131I-meta-iodobenzylguanidine with
      topotecan as a radiosensitizer in children with metastatic neuroblastoma.
AB  - INTRODUCTION: (131)I-meta iodobenzylguanidine ((131)I-mIBG) therapy is
      established palliation for relapsed neuroblastoma. The topoisomerase-1 inhibitor,
      topotecan, has direct activity against neuroblastoma and acts as a radiation
      sensitiser. These 2 treatments are synergistic in laboratory studies.
      Theoretically, the benefit of (131)I-mIBG treatment could be enhanced by dose
      escalation and combination with topotecan. Haematological support would be
      necessary to overcome the myelosuppression, which is the dose-limiting toxicity.
      AIMS: Firstly, one aim of this study was to establish whether in vivo dosimetry
      could be used to guide the delivery of a precise total whole-body radiation
      absorbed dose of 4 Gy accurately from 2 (131)I-mIBG treatments. Secondly, the
      other aim of this study was to determine whether it is feasible to combine this
      treatment with the topotecan in children with metastatic neuroblastoma. MATERIAL
      AND METHODS: An activity of (131)I-mIBG (12 mCi/kg, 444 MBq/kg), estimated to
      give a whole-body absorbed-radiation dose of approximately 2 Gy, was administered
      on day 1, with topotecan 0.7 mg/m(2) administered daily from days 1-5. In vivo
      dosimetry was used to calculate a 2nd activity of (131)I-mIBG, to be given on day
      15 which would give a total whole-body dose of 4 Gy. A further 5 doses of
      topotecan were given from days 15-19. The myeloablative effect of this regimen
      was circumvented by peripheral blood stem cell or bone marrow support. RESULTS:
      Eight children with relapsed stage IV neuroblastoma were treated. The treatment
      was delivered according to protocol in all patients. There were no unanticipated
      side-effects. Satisfactory haematological reconstitution occurred in all
      patients. The measured total whole-body radiation-absorbed dose ranged from 3.7
      Gy to 4.7 Gy (mean, 4.2 Gy). CONCLUSIONS: In vivo dosimetry allows for a
      specified total whole-body radiation dose to be delivered accurately. This
      schedule of intensification of (131)I-mIBG therapy by dose escalation and
      radiosensitization with topotecan with a haemopoietic autograft is safe and
      practicable. This approach should now be tested for efficacy in a phase II
      clinical trial.

PMID- 15869456
TI  - Selective internal radiation therapy with SIR-Spheres in patients with
      nonresectable liver tumors.
AB  - AIM: Transarterial embolization of branches of the hepatic artery with
      biocompatible 90Y-labeled microspheres (SIR-Spheres) is a local treatment
      modality for patients with liver tumors, which, most recently, has become
      available in Europe. The aim of this study was to evaluate the feasibility and
      efficacy of this selective internal radiation therapy (SIRT). METHODS: Twenty
      three patients with nonresectable hepatic metastases or hepatocellular carcinoma
      nonresponding to polychemotherapy and/or other local treatment were treated with
      SIRT. SIR-Spheres (mean activity, 2270 MBq) were administered by gentle intra
      arterial infusion in the hepatic artery. A follow-up was documented by
      fluorodeoxyglucose-positron emission tomography (FDG-PET), course of tumor
      markers, and computed tomography (CT). RESULTS: Common minor side-effects were
      abdominal pain, nausea, and fever. Mild pancreatitis and peptic ulceration were
      observed once each. Currently, all patients are still alive, with survival times
      ranging from 11 to 518 days from SIRT up to the present. Three-month follow-up
      investigations are available in 13 of 23 patients, which, so far, are showing a
      marked decrease of FDG uptake, a drop of tumor markers, and unchanged or slightly
      decreasing lesion size (CT) in 10 of 13 patients. Two patients showed stable
      findings, while another patient showed progressive disease. Long-term follow-up
      investigations are available in 2 of 23 patients, showing hepatic and
      extrahepatic progression 6 and 9 months after SIRT. CONCLUSIONS: Our initial
      experience confirms that SIRT is a promising local therapeutic approach in
      patients with nonresectable liver tumors which is feasible and has an acceptable
      toxicity profile. Prospective data on comparing this treatment alone or in
      combination with other modalities are needed to answer whether long-term survival
      in this unfavorable stage of disease can be markedly improved.

PMID- 15869457
TI  - Radiolabeled lipiodol therapy for hepatocellular carcinoma in patients awaiting
      liver transplantation: pathology of the explant livers and clinical outcome.
AB  - BACKGROUND: Liver transplantation has become an important curative treatment
      option for hepatocellular carcinoma (HCC). Criteria for transplantation are
      strict and, therefore, it is crucial that patients awaiting transplantation do
      not suffer disease progression. One of the therapeutic options to achieve disease
      stabilization is neoadjuvant radiolabeled lipiodol treatment. This study aimed to
      document the dropout rate on the waiting list, the pathological findings on the
      explant livers, and the long-term outcome of patients treated with radionuclide
      therapy while awaiting transplantation. METHODS: Patients eligible for
      transplantation were treated with 2.1 GBq (131)I-lipiodol or 4.1 GBq (188)Re
      HDD/lipiodol by transfemoral catheterization of the hepatic arteries. Tumor
      necrosis was assessed in the explant livers and follow-up data, such as dropout
      from the waiting list, recurrence, and survival following transplantation were
      retrospectively documented. RESULTS: In 5 of 22 explants, necrosis exceeded 90%.
      Two patients died while on the waiting list (10%) and 4 of 20 transplanted
      patients (20%) suffered recurrent disease. The overall recurrence-free survival
      was 19.7 months (range, 1.75-56), with a mean follow-up of 20.1 months.
      CONCLUSION: Our data support the evaluation on larger patient numbers to confirm
      the benefit of radiolabeled lipiodol in candidates for liver transplantation who
      are suffering from HCC.

PMID- 15869458
TI  - Evaluation of the therapeutic response to In-111-DTPA octreotide-based targeted
      therapy in liver metastatic neuroendocrine tumors according to CT/MRI/US
      findings.
AB  - Thirteen (13) patients with liver neuroendocrine carcinomas metastases, positive
      for somatostatin receptors, confirmed by scintigraphy were infused with 4070-7030
      MBq per session of In-111-octreotide after selective hepatic catheterization,
      exploiting the catastrophic activity of Indium Auger and Internal Conversion
      electron emission on cell DNA. Evaluation of the treatment was assessed by
      ultrasonography (US) as well as by computed tomography and/or magnetic resonance
      imaging scans. US appears to be the imaging procedure of choice because the
      examination is sensitive for evaluating lesions' edema and cystic components,
      provides precise measurement of tumor size, and is inexpensive. Degeneration US
      signs were classified in stage I (an echolucent rim in the periphery of the
      lesion), stage IIa (lesion with large cystic spaces), stage IIb (tiny cystic
      spaces) and stage III (absorption of the cystic component or stable cystic
      remnants).

PMID- 15869459
TI  - Comparison of different thyroid committed doses in radioiodine therapy for
      Graves' hyperthyroidism.
AB  - Despite vast worldwide experience in the use of 131I for treating Graves' disease
      (GD), no consensus of opinion exists concerning the optimal method of dose
      calculation. In one of the most popular equations, the administered (131)I dose
      is directly proportional to the estimated thyroid gland volume and inversely
      proportional to the measured 24-hour radioiodine uptake. In this study, we
      compared the efficiency of different tissue-absorbed doses to induce euthyroidism
      or hypothyroidism within 1 year after radioiodine therapy in GD patients. The
      study was carried out in 134 GD patients (age, 53 +/- 14 year; range, 16-82 year;
      thyroid volume, 28 +/- 18 mL; range, 6-95 mL; average 24-hour thyroid uptake,
      72%) treated with (131)I therapy. The average radioiodine activity administered
      to patients was 518 +/- 226 MBq (range, 111-1110). The corresponding average
      thyroid absorbed dose, calculated by a modified Medical Internal Radiation Dose
      (MIRD) equation was 376 +/- 258 Gy (range, 99-1683). One year after treatment, 58
      patients (43%) were hypothyroid, 57 patients (43%) were euthyroid, and 19
      patients (14%) remained hyperthyroid. The patients were divided into 3 groups:
      150 Gy (n = 32), 300 Gy (n = 58) and >300 Gy (n = 44). No significant difference
      in the rate of recurrent hyperthyroidism was found among the 3 groups (150 Gy:
      15%; 300 Gy: 14%; and > or =300 Gy: 14%; chi-square test, p = 0.72). Whereas, the
      rate of hypothyroidism in the 3 groups was significantly correlated with the dose
      (150 Gy: 30%; 300 Gy: 46%; >300 Gy: 71%; chi-square test, p = 0.0003). The
      results obtained in this study show no correlation between dose and outcome of
      radioiodine therapy (in terms of persistent hyperthyroidism) for thyroid absorbed
      doses > or =150 Gy, while confirming the relation between the thyroid absorbed
      dose and the incidence of hypothyroidism in GD patients.

PMID- 15869460
TI  - Internal microdosimetry for single cells in radioimmunotherapy of B-cell
      lymphoma.
AB  - Patients with B-cell lymphoma may have disease manifestations ranging in size
      from more than a 1000 cm3 down to the volume of a single cell. If targeted
      radionuclide therapy is to become a curative treatment, all individual tumor
      cells must also be eliminated. Given the vast differences in particle energy of
      different electron- emitting radionuclides, one questions whether the mean
      absorbed dose is a relevant parameter for use in single-cell dosimetry and
      whether it would not be more accurate to adopt a stochastic approach to
      dosimetry. Monte Carlo simulations were performed of energy deposition from 1000,
      300, 100, or 10 electrons uniformly distributed in a sphere with a radius of 7.7
      microm. The simulated electrons were monoenergetic (18 keV, 28 keV, 141 keV, or
      935 keV). The absorbed dose per emitted electron, the absorbed fraction, the
      fraction of the cellular volume in which energy is deposited, and the dose-volume
      histograms were calculated. Absorbed fractions varied between 0.60 (18 keV) and
      0.001 (935 keV), and the absorbed dose to the cell per electron emitted varied by
      a factor of 10, from 0.898 mGy (18 keV) to 0.096 mGy (935 keV). The specific
      energy varied between 0 and 46 mGy for the case showing the best uniformity (1000
      18-keV electrons). The nonuniformity of the absorbed dose to a cell increases
      with increasing electron energy and decreases with the number of decays inside
      the studied volume. The wide distribution of energy deposition should be taken
      into account when analyzing and designing trials for targeted radionuclide
      therapy.

PMID- 15869461
TI  - Differences in biodistribution between 99mTc-depreotide, 111In-DTPA-octreotide,
      and 177Lu-DOTA-Tyr3-octreotate in a small cell lung cancer animal model.
AB  - AIM: (177)Lu-DOTA-Tyr(3)-octreotate is a candidate radiopharmaceutical for the
      therapy of somatostatin receptor (sstr)-positive small cell lung cancer (SCLC).
      Scintigraphy of lung tumors is made with 2 alternative somatostatin analogs,
      (111)In-DTPA-octreotide or (99m)Tc-depreotide. The aim of this study was to
      compare the biodistribution of these 3 radiopharmaceuticals in SCLC xenografted
      to nude mice. METHODS: Nude mice, bearing tumors from the human SCLC cell line
      NCI-H69, were intravenously injected with 10 MBq (2.4 microg) (99m)Tc-depreotide
      and 2 MBq (0.5 microg) (111)In-DTPA-octreotide simultaneously. The activity
      concentration (%IA/g) was measured in tumor and normal tissue at 2, 4, and 24
      hours postinjection (hpi). The results were compared with earlier published
      biodistribution data of 3 MBq (0.7 microg) (177)Lu-DOTA-Tyr(3)-octreotate in the
      same animal model. RESULTS: The activity concentration of (111)In-DTPAoctreotide
      in tumor was higher than the activity concentration of (99m)Tc-depreotide at 2-24
      hpi, p < 0.05. The highest tumor uptake at 24 hpi was, however, found for (177)Lu
      DOTA-Tyr(3)-octreotate. The activity concentration of (99m)Tc-depreotide was
      significantly higher in the heart, lungs, liver, the salivary glands, spleen, and
      bone marrow than for (111)In-DTPA-octreotide at 2-24 hpi. Saturation of the
      somatostatin receptors may have influenced the uptake in tumor and sstr-positive
      normal tissues. CONCLUSION: The low tumor-to-lung and tumor-to-liver activity
      concentration ratios for (99m)Tc-depreotide could result in a lower detection
      rate of SCLC with this compound versus (111)In-DTPA-octreotide. (177)Lu-DOTA
      Tyr(3)-octreotate gave the highest tumor-activity concentration, and has, thus,
      the best properties for therapy.

PMID- 15869463
TI  - Activation of hepatocyte growth factor by urokinase-type plasminogen activator is
      ionic strength-dependent.
AB  - The hepatocyte growth factor (HGF) is a multifunctional cytokine that is produced
      as latent scHGF (single chain HGF). Various proteases reportedly cleave scHGF to
      generate the active two-chain form (HGF), including u-PA (urokinase-type
      plasminogen activator), t-PA (tissue-type plasminogen activator), kallikrein,
      Factor XIa, Factor XIIa, HGF activator and matriptase. Considerable evidence
      indicates that, in vivo, u-PA activates scHGF in the liver; however, the in vivo
      results have not been uniformly supported by in vitro experiments. We now report
      that cleavage of scHGF by high-molecular-mass u-PA (abbreviated u-PA throughout)
      is sensitive to ionic strength. scHGF cleavage by u-PA was accelerated as the
      ionic strength was decreased. This result was equivalent irrespective of whether
      the predominant anion was chloride or acetate. Lmw-u-PA (low-molecular-mass u-PA)
      was ineffective at cleaving scHGF, regardless of ionic strength. Although scHGF
      shares homology with plasminogen, EACA (-amino-caproic acid) did not regulate u
      PA-mediated scHGF cleavage. Soluble HGF receptor (MET) and soluble u-PAR (u-PA
      receptor) inhibited the scHGF cleavage. These results support a model in which
      the ability of u-PA to activate scHGF in vivo may be highly dependent on local
      conditions within the extracellular space.

PMID- 15869464
TI  - Post-translationally modified residues of native human osteopontin are located in
      clusters: identification of 36 phosphorylation and five O-glycosylation sites and
      their biological implications.
AB  - OPN (osteopontin) is an integrin-binding highly phosphorylated glycoprotein,
      recognized as a key molecule in a multitude of biological processes such as bone
      mineralization, cancer metastasis, cell-mediated immune response, inflammation
      and cell survival. A significant regulation of OPN function is mediated through
      PTM (post-translational modification). Using a combination of Edman degradation
      and MS analyses, we have characterized the complete phosphorylation and
      glycosylation pattern of native human OPN. A total of 36 phosphoresidues have
      been localized in the sequence of OPN. There are 29 phosphorylations (Ser8,
      Ser10, Ser11, Ser46, Ser47, Thr50, Ser60, Ser62, Ser65, Ser83, Ser86, Ser89,
      Ser92, Ser104, Ser110, Ser113, Thr169, Ser179, Ser208, Ser218, Ser238, Ser247,
      Ser254, Ser259, Ser264, Ser275, Ser287, Ser292 and Ser294) located in the target
      sequence of MGCK (mammary gland casein kinase) also known as the Golgi kinase
      (S/T-X-E/S(P)/D). Six phosphorylations (Ser101, Ser107, Ser175, Ser199, Ser212
      and Ser251) are located in the target sequence of CKII (casein kinase II) [S-X-X
      E/S(P)/D] and a single phosphorylation, Ser203, is not positioned in the motif of
      either MGCK or CKII. The 36 phosphoresidues represent the maximal degree of
      modification since variability at many sites was seen. Five threonine residues
      are O-glycosylated (Thr118, Thr122, Thr127, Thr131 and Thr136) and two potential
      sites for N-glycosylation (Asn63 and Asn90) are not occupied in human milk OPN.
      The phosphorylations are arranged in clusters of three to five phosphoresidues
      and the regions containing the glycosylations and the RGD (Arg-Gly-Asp) integrin
      binding sequence are devoid of phosphorylations. Knowledge about the positions
      and nature of PTMs in OPN will allow a rational experimental design of functional
      studies aimed at understanding the structural and functional interdependences in
      diverse biological processes in which OPN is a key molecule.

PMID- 15869465
TI  - Investigation of the catalytic triad of arylamine N-acetyltransferases: essential
      residues required for acetyl transfer to arylamines.
AB  - The NATs (arylamine N-acetyltransferases) are a well documented family of enzymes
      found in both prokaryotes and eukaryotes. NATs are responsible for the
      acetylation of a range of arylamine, arylhydrazine and hydrazine compounds. We
      present here an investigation into the catalytic triad of residues (Cys-His-Asp)
      and other structural features of NATs using a variety of methods, including site
      directed mutagenesis, X-ray crystallography and bioinformatics analysis, in order
      to investigate whether each of the residues of the catalytic triad is essential
      for catalytic activity. The catalytic triad of residues, Cys-His-Asp, is a well
      defined motif present in several families of enzymes. We mutated each of the
      catalytic residues in turn to investigate the role they play in catalysis. We
      also mutated a key residue, Gly126, implicated in acetyl-CoA binding, to examine
      the effects on acetylation activity. In addition, we have solved the structure of
      a C70Q mutant of Mycobacterium smegmatis NAT to a resolution of 1.45 A (where 1
      A=0.1 nm). This structure confirms that the mutated protein is correctly folded,
      and provides a structural model for an acetylated NAT intermediate. Our
      bioinformatics investigation analysed the extent of sequence conservation between
      all eukaryotic and prokaryotic NAT enzymes for which sequence data are available.
      This revealed several new sequences, not yet reported, of NAT paralogues.
      Together, these studies have provided insight into the fundamental core of NAT
      enzymes, and the regions where sequence differences account for the functional
      diversity of this family. We have confirmed that each of the three residues of
      the triad is essential for acetylation activity.

PMID- 15869466
TI  - The semi-phosphorylative Entner-Doudoroff pathway in hyperthermophilic archaea: a
      re-evaluation.
AB  - Biochemical studies have suggested that, in hyperthermophilic archaea, the
      metabolic conversion of glucose via the ED (Entner-Doudoroff) pathway generally
      proceeds via a non-phosphorylative variant. A key enzyme of the non
      phosphorylating ED pathway of Sulfolobus solfataricus, KDG (2-keto-3
      deoxygluconate) aldolase, has been cloned and characterized previously. In the
      present study, a comparative genomics analysis is described that reveals
      conserved ED gene clusters in both Thermoproteus tenax and S. solfataricus. The
      corresponding ED proteins from both archaea have been expressed in Escherichia
      coli and their specificity has been identified, revealing: (i) a novel type of
      gluconate dehydratase (gad gene), (ii) a bifunctional 2-keto-3-deoxy-(6-phospho)
      gluconate aldolase (kdgA gene), (iii) a 2-keto-3-deoxygluconate kinase (kdgK
      gene) and, in S. solfataricus, (iv) a GAPN (non-phosphorylating glyceraldehyde-3
      phosphate dehydrogenase; gapN gene). Extensive in vivo and in vitro enzymatic
      analyses indicate the operation of both the semi-phosphorylative and the non
      phosphorylative ED pathway in T. tenax and S. solfataricus. The existence of this
      branched ED pathway is yet another example of the versatility and flexibility of
      the central carbohydrate metabolic pathways in the archaeal domain.

PMID- 15869467
TI  - Oxygenation by COX-2 (cyclo-oxygenase-2) of 3-HETE (3-hydroxyeicosatetraenoic
      acid), a fungal mimetic of arachidonic acid, produces a cascade of novel
      bioactive 3-hydroxyeicosanoids.
AB  - Cyclo-oxygenases-1/2 (COX-1/2) catalyse the oxygenation of AA (arachidonic acid)
      and related polyunsaturated fatty acids to endoperoxide precursors of
      prostanoids. COX-1 is referred to as a constitutive enzyme involved in
      haemostasis, whereas COX-2 is an inducible enzyme expressed in inflammatory
      diseases and cancer. The fungus Dipodascopsis uninucleata has been shown by us to
      convert exogenous AA into 3(R)-HETE [3(R)-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic
      acid]. 3R-HETE is stereochemically identical with AA, except that a hydroxy group
      is attached at its C-3 position. Molecular modelling studies with 3-HETE and COX
      1/2 revealed a similar enzyme-substrate structure as reported for AA and COX-1/2.
      Here, we report that 3-HETE is an appropriate substrate for COX-1 and -2, albeit
      with a lower activity of oxygenation than AA. Oxygenation of 3-HETE by COX-2
      produced a novel cascade of 3-hydroxyeicosanoids, as identified with EI (electron
      impact)-GC-MS, LC-MS-ES (electrospray) and LC-MS-API (atmospheric pressure
      ionization) methods. Evidence for in vitro production of 3-hydroxy-PGE2 (3
      hydroxy-prostaglandin E2) was obtained upon infection of HeLa cells with Candida
      albicans at an MOI (multiplicity of infection) of 100. Analogous to interaction
      of AA and aspirin-treated COX-2, 3-HETE was transformed by acetylated COX-2 to
      3,15-di-HETE (3,15-dihydroxy-HETE), whereby C-15 showed the (R)-stereochemistry.
      3-Hydroxy-PGs are potent biologically active compounds. Thus 3-hydroxy-PGE2
      induced interleukin-6 gene expression via the EP3 receptor (PGE2 receptor 3) in
      A549 cells, and raised cAMP levels via the EP4 receptor in Jurkat cells.
      Moreover, 3R,15S-di-HETE triggered the opening of the K+ channel in HTM (human
      trabecular meshwork) cells, as measured by the patch-clamp technique. Since many
      fatty acid disorders are associated with an 'escape' of 3-hydroxy fatty acids
      from the b-oxidation cycle, the production of 3-hydroxyeicosanoids may be
      critical in modulation of effects of endogenously produced eicosanoids.

PMID- 15869468
TI  - Importance of N-glycosylation positioning for cell-surface expression, targeting,
      affinity and quality control of the human AT1 receptor.
AB  - GPCRs (G-protein-coupled receptors) are preferentially N-glycosylated on ECL2
      (extracellular loop 2). We previously showed that N-glycosylation of ECL2 was
      crucial for cell-surface expression of the hAT1 receptor (human angiotensin II
      receptor subtype 1). Here, we ask whether positioning of the N-glycosylation
      sites within the various ECLs of the receptor is a vital determinant in the
      functional expression of hAT(1) receptor at the cell surface. Artificial N
      glycosylation sequons (Asn-Xaa-Ser/Thr) were engineered into ECL1, ECL2 and ECL3.
      N-glycosylation of ECL1 caused a very significant decrease in affinity and cell
      surface expression of the resulting receptor. Shifting the position of the ECL2
      glycosylation site by two residues led to the synthesis of a misfolded receptor
      which, nevertheless, was trafficked to the cell surface. The misfolded nature of
      this receptor is supported by an increased interaction with the chaperone HSP70
      (heat-shock protein 70). Introduction of N-glycosylation motifs into ECL3 yielded
      mutant receptors with normal affinity, but low levels of cell surface expression
      caused by proteasomal degradation. This behaviour differed from that observed for
      the aglycosylated receptor, which accumulated in the endoplasmic reticulum. These
      results show how positioning of the N-glycosylation sites altered many properties
      of the AT1 receptor, such as targeting, folding, affinity, cell surface
      expression and quality control.

PMID- 15869469
TI  - Bacillus subtilis 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase revisited:
      resolution of two long-standing enigmas.
AB  - The mono/bifunctional and metallo/non-metallo properties of Bacillus subtilis
      DAHPS (3-deoxy-D-arabino-heptulosonate 7-phosphate synthase) have been
      controversial for several decades. The present study investigated the DAHPSs from
      both the B. subtilis parent Marburg strain and the derivative strain 168 in
      detail and clarified the above two long-standing questions. The DAHPSs from the
      parent and the derivative 168 strains have identical sequence and are both
      bifunctional enzymes with a CM (chorismate mutase) activity and a DAHPS activity.
      The parent strain expresses a second independent monofunctional CM, encoded by
      aroH, that is highly active, while the 168 strain expresses an aroH containing a
      single residue mutation (A112V) that is significantly less active thus leading to
      previous confusion regarding the mono/bifunctionality of DAHPS. Metal analysis
      showed that B. subtilis DAHPS as isolated contained iron and zinc and is
      inactivated by dipicolinic acid; the inactive apoenzyme can be reactivated by
      bivalent metal ions, indicating that the enzyme is a metalloenzyme. The enzyme
      bound metal is insensitive to EDTA treatment, leading to the previous conclusion
      that this DAHPS does not require a metal. The enzyme displays a homotetrameric
      structure in solution and appears to follow Michaelis-Menten kinetics with
      K(m)(PEP)=139+/-11.4 microM for phosphoenolpyruvate, K(m)(E4P)=1760+/-110 microM
      for D-erythrose 4-phosphate, kcat=4.6+/-0.1 s(-1) for DAHPS activity and
      K(m)(chorismate)=850+/-97 microM, kcat=0.41+/-0.01 s(-1) for CM activity. B.
      subtilis DAHPS is inhibited by the Shikimate pathway intermediates prephenate and
      chorismate.

PMID- 15869470
TI  - Crystal structure of levansucrase from the Gram-negative bacterium
      Gluconacetobacter diazotrophicus.
AB  - The endophytic Gram-negative bacterium Gluconacetobacter diazotrophicus SRT4
      secretes a constitutively expressed levansucrase (LsdA, EC 2.4.1.10), which
      converts sucrose into fructooligosaccharides and levan. The enzyme is included in
      GH (glycoside hydrolase) family 68 of the sequence-based classification of
      glycosidases. The three-dimensional structure of LsdA has been determined by X
      ray crystallography at a resolution of 2.5 A (1 A=0.1 nm). The structure was
      solved by molecular replacement using the homologous Bacillus subtilis (Bs)
      levansucrase (Protein Data Bank accession code 1OYG) as a search model. LsdA
      displays a five-bladed beta-propeller architecture, where the catalytic residues
      that are responsible for sucrose hydrolysis are perfectly superimposable with the
      equivalent residues of the Bs homologue. The comparison of both structures, the
      mutagenesis data and the analysis of GH68 family multiple sequences alignment
      show a strong conservation of the sucrose hydrolytic machinery among
      levansucrases and also a structural equivalence of the Bs levansucrase Ca2+
      binding site to the LsdA Cys339-Cys395 disulphide bridge, suggesting similar fold
      stabilizing roles. Despite the strong conservation of the sucrose-recognition
      site observed in LsdA, Bs levansucrase and GH32 family Thermotoga maritima
      invertase, structural differences appear around residues involved in the
      transfructosylation reaction.

PMID- 15869471
TI  - Abstracts from the American Society for Reproductive Immunology (ASRI) 25th
      Anniversary Meeting. Providence, Rhode Island, USA, June 16-18, 2005.

PMID- 15869472
TI  - A semaphorin code defines subpopulations of spinal motor neurons during mouse
      development.
AB  - Abstract In the spinal cord, motor neurons (MNs) with similar muscle targets and
      sensory inputs are grouped together into motor pools. To date, relatively little
      is known about the molecular mechanisms that control the establishment of pool
      specific circuitry. Semaphorins, a large family of secreted and cell surface
      proteins, are important mediators of developmental processes such as axon
      guidance and cell migration. Here, we used mRNA in situ hybridization to study
      the expression patterns of semaphorins and their receptors, neuropilins and
      plexins, in the embryonic mouse spinal cord. Our data show that semaphorins and
      their receptors are differentially expressed in MNs that lie in distinct
      locations within the spinal cord. Furthermore, we report a combinatorial
      expression of class 3 (secreted) semaphorins and their receptors that
      characterizes distinct motor pools within the brachial and lumbar spinal cord.
      Finally, we found that a secreted semaphorin, Sema3A, elicits differential
      collapse responses in topologically distinct subpopulations of spinal MNs. These
      findings lead us to propose that semaphorins and their receptors might play
      important roles in the sorting of motor pools and the patterning of their
      afferent and efferent projections.

PMID- 15869473
TI  - Spontaneous electrical activity and dendritic spine size in mature cerebellar
      Purkinje cells.
AB  - Previous experiments have shown that in the mature cerebellum both blocking of
      spontaneous electrical activity and destruction of the climbing fibres by a
      lesion of the inferior olive have a similar profound effect on the spine
      distribution on the proximal dendrites of the Purkinje cells. Many new spines
      develop that are largely innervated by parallel fibers. Here we show that
      blocking electrical activity leads to a significant decrease in size of the
      spines on the branchlets. We have also compared the size of the spines of the
      proximal dendritic domain that appear during activity block and after an inferior
      olive lesion. In this region also, the spines in the absence of activity are
      significantly smaller. In the proximal dendritic domain, the new spines that
      develop in the absence of activity are innervated by parallel fibers and are not
      significantly different in size from those of the branchlets, although they are
      shorter. Thus, the spontaneous activity of the cerebellar cortex is necessary not
      only to maintain the physiological spine distribution profile in the Purkinje
      cell dendritic tree, but also acts as a signal that prevents spines from
      shrinking.

PMID- 15869475
TI  - Cortical origin of functional recovery in the somatosensory cortex of the adult
      mouse after thalamic lesion.
AB  - To study the degree and time course of the functional recovery in the
      somatosensory cortex (SI) after an excitotoxic lesion in the adult mouse
      thalamus, metabolic activity was determined in SI at various times points post
      lesion. Immediately after the lesion, metabolic activity in the thalamically
      deafferented part of SI was at its lowest value but increased progressively at
      subsequent time points. This was seen in all cortical layers; however, layers I
      and Vb recovered more rapidly than layers II, III, IV, Va and VI. Removal of the
      mystacial whiskers corresponding to the deafferented area, 5 weeks after cortical
      recovery, produced a subsequent 32% drop in metabolic activity, demonstrating
      peripheral sensory activation of this part of the cortex. Tracing experiments
      revealed that the deafferented cortex did not receive a novel thalamic input but
      that cortico-cortical and contralateral barrel cortex projections to this area
      were reinforced. We conclude that the cortical functional recovery after a
      thalamic lesion is, at least partially, due to modified cortico-cortical and
      callosal projections to the deafferented cortical area.

PMID- 15869474
TI  - Activity-dependent phosphorylation of Akt/PKB in adult DRG neurons.
AB  - The serine/threonine kinase Akt/PKB has been implicated in cell survival
      signalling in many cell types, including the dorsal root ganglion (DRG). However,
      little is known about its role in physiological and pathophysiological conditions
      in the adult sensory and nociceptive system. In this study, we show that in naive
      animals almost all cells express Akt but only a subset of small-diameter neurons
      expresses a high level of phospho-Akt (p-Akt Ser 473). Activation of peripheral
      nociceptors in vivo using intraplantar injections of capsaicin in anaesthetized
      rats induced a rapid onset and time-dependent increase in p-Akt Ser 473 in small-
      and medium-sized DRG, predominantly TRPV1-positive neurons. In addition,
      electrical stimulation of 'A and C' fibres in the sciatic nerve induced an
      increase in the cytoplasmic staining of p-Akt Ser 473 in small- and medium-size
      DRG neurons. Blocking neuronal activity in the sciatic nerve using tetrodotoxin
      reduced the basal level of p-Akt Ser 473. Cultured DRG neurons confirmed that
      phosphorylation of Akt in different cellular compartments is triggered by
      depolarization or receptor activation, and suggested that this effect is mediated
      in part by phosphatidylinositol 3-kinase. Our results show that p-Akt Ser 473 is
      a marker of nociceptor activation and suggest a novel role for Akt in the
      transduction of intracellular signals in adult DRG neurons.

PMID- 15869476
TI  - Selective cholinergic immunolesioning affects synaptic plasticity in developing
      visual cortex.
AB  - Cholinergic neurotransmission is known to affect activity-dependent plasticity in
      various areas, including the visual cortex. However, relatively little is known
      about the exact role of subcortical cholinergic inputs in the regulation of
      plastic events in this region during early postnatal development. In the present
      study, synaptic transmission and plasticity in the developing visual cortex were
      studied following selective immunotoxic removal of the basal forebrain
      cholinergic afferents in 4-day-old rat pups. The lesion produced dramatic
      cholinergic neuronal and terminal fibre loss associated with decreased mRNA
      levels for the M1 and M2 muscarinic receptors, as well as clear-cut impairments
      of long-term potentiation (LTP) in visual cortex slices. Indeed, after theta
      burst stimulation of layer IV a long-term depression (LTD) instead of an LTP was
      induced in immunolesioned slices. This functional change appears to be due to the
      lack of cholinergic input as exogenous application of acetylcholine prevented the
      shift from LTP to LTD. In addition, lesioned rats showed an increased sensitivity
      to acetylcholine (ACh). While application of 20 microm ACh produced a depression
      of the field potential in immunolesioned rat slices, in order to observe the same
      effect in control slices we had to increase ACh concentration to up to 200
      microm. Taken together, our results indicate that deprivation of cholinergic
      input affects synaptic transmission and plasticity in developing visual cortex,
      suggesting that the cholinergic system could play an active role in the
      refinement of the cortical circuitry during maturation.

PMID- 15869477
TI  - Striatal expression of GDNF and differential vulnerability of midbrain
      dopaminergic cells.
AB  - Glial cell line-derived neurotrophic factor (GDNF) is a member of the
      transforming growth factor-beta superfamily that when exogenously administrated
      exerts a potent trophic action on dopaminergic (DA) cells. Although we know a lot
      about its signalling mechanisms and pharmacological effects, physiological
      actions of GDNF on the adult brain remain unclear. Here, we have used
      morphological and molecular techniques, and an experimental model of Parkinson's
      disease in rats, to investigate whether GDNF constitutively expressed in the
      adult mesostriatal system plays a neuroprotective role on midbrain DA cells. We
      found that although all midbrain DA cells express both receptor components of
      GDNF (GFRalpha1 and Ret), those in the ventral tegmental area (VTA) and
      rostromedial substantia nigra (SNrm) also contain GDNF but not GDNFmRNA. The
      levels of GDNFmRNA are significantly higher in the ventral striatum (vSt), the
      target region of VTA and SNrm cells, than in the dorsal striatum (dSt), the
      target region of DA cells in the caudoventral substantia nigra (SNcv). After
      fluoro-gold injection in striatum, VTA and SNrm DA cells show triple labelling
      for tyrosine hydroxylase, GDNF and fluoro-gold, and after colchicine injection in
      the lateral ventricle, they become GDNF-immunonegative, suggesting that GDNF in
      DA somata comes from their striatal target. As DA cells in VTA and SNrm are more
      resistant than those in SNcv to intracerebroventricular injection of 6-OHDA, as
      occurs in Parkinson's disease, we can suggest that the fact that they project to
      vSt, where GDNF expression is significantly higher than in the dSt, is a
      neuroprotective factor involved in the differential vulnerability of midbrain DA
      neurons.

PMID- 15869478
TI  - A pentylenetetrazole-induced generalized seizure in early life enhances the
      efficacy of muscarinic receptor coupling to G-protein in hippocampus and
      neocortex of adult rat.
AB  - We have previously shown that exposure to the anti-cholinesterase eserine
      provokes interictal-like discharges in the CA3 area of hippocampal slices from
      adult rats in which a generalized seizure has been induced by pentylenetetrazole
      (PTZ) when immature (at 20 days). Such increased responsiveness to acetylcholine
      (ACh) was not associated with any change in hippocampal acetylcholine or gamma
      aminobutyric acid (GABA) content, GABAergic inhibition or density of ACh
      innervation, but was blocked by the muscarinic receptor antagonist atropine. We
      therefore turned to quantitative radioligand binding autoradiography, in situ
      hybridization and the [35S]GTPgammaS method to assess the properties of
      hippocampal and neocortical muscarinic receptors in adult rats having experienced
      a PTZ seizure at P20. The densities of M1 and M2 receptor binding sites,
      respectively labeled with [3H]pirenzepine and [3H]AFDX-384, as well as the amount
      of m1, m2 and m3 receptor mRNAs, did not differ from control in the hippocampus
      and neocortex of these rats. In contrast, in PTZ rats, both brain regions
      displayed a marked increase in [35S]GTPgammaS incorporation stimulated by ACh,
      bethanechol and particularly oxotremorine. This finding indicates that a
      generalized seizure in immature rat can entail a long-term and presumably
      permanent increase in the efficacy of G-protein coupling to muscarinic receptors
      in the hippocampus and neocortex of the adult. By analogy, such a mechanism could
      account for the susceptibility to epilepsy of human adults having suffered from
      prolonged convulsions in early life.

PMID- 15869479
TI  - Midbrain muscarinic receptor mechanisms underlying regulation of mesoaccumbens
      and nigrostriatal dopaminergic transmission in the rat.
AB  - Laterodorsal (LDT) and pedunculopontine (PPT) tegmental nuclei in the mesopontine
      project cholinergic inputs to the midbrain ventral tegmental area (VTA) and
      substantia nigra pars compacta (SNc), respectively, to directly and indirectly
      influence the activity of dopamine neuronal cells via actions on muscarinic and
      nicotinic receptors. The present study investigated the role of midbrain
      muscarinic receptors in the functional modulation of VTA and SNc dopamine cell
      activity as reflected by alterations in, respectively, nucleus accumbens (NAc)
      and striataldopamine efflux. In vivo chronoamperometry was used to measure
      changes in basal dopamine efflux via stearate-graphite paste electrodes implanted
      unilaterally in the NAc or striatum of urethane-anaesthetized rats, following
      blockade or activation of, respectively, VTA or SNc muscarinic receptors. Intra
      VTA or -SNc infusion of the muscarinic antagonist scopolamine (200 microg/microL)
      reduced, respectively, NAc and striatal dopamine efflux while infusion of the
      muscarinic and nicotinic agonist carbachol (0.5 microg/microL) or the
      prototypical muscarinic agonist muscarine (0.5 microg/microL) increased NAc and
      striatal dopamine efflux. Transient decreases in dopamine efflux preceded these
      increases selectively in the striatum, suggesting a reduction in excitatory or
      increase in inhibitory drive to the SNc by preferential activation of M3
      muscarinic receptors on GABA interneurons and glutamatergic inputs. This was
      confirmed by showing that selective blockade of M3 receptors with p-F-HHSiD (0.5
      microg/microL) increased striatal, but not NAc, dopamine efflux. Together, these
      findings suggest that midbrain muscarinic receptors, probably M5 subtypes on VTA
      and SNc dopamine neurons, contribute to the tonic excitatory regulation of
      forebrain basal dopamine transmission whereas presynaptic M3 receptors serve to
      counter excessive excitation of nigral dopamine cell activity.

PMID- 15869480
TI  - Multiple defects in the formation of rat cortical axonal pathways following
      prenatal X-ray irradiation.
AB  - Prenatal X-ray irradiation is known to result in severe defects of neuronal
      migration and laminar formation in the cerebral cortex. We examined the formation
      of cortical afferent and efferent pathways in rats that had been exposed to X-ray
      irradiation (1.0 Gy) at embryonic day 14 (E14), by birthdating with
      bromodeoxyuridine (BrdU) and axonal labeling with 1-1'-dioctodecyl-3,3,3',3'-
      tetramethyl-indocarbocyanine perchlorate (DiI), in addition to
      immunohistochemical staining for various axonal markers including neurofilament,
      and cell adhesion molecules L1 and TAG-1. The results obtained were as follows.
      (i) The neuroepithelium formed germinal rosettes and concavities in the cortical
      anlage from 2 days after irradiation. Neurons generated in the neuroepithelium
      accumulated to form subcortical heterotopia and obstructed pathway formation in
      the intermediate zone, resulting in an aberrant trajectory of TAG-1
      immunoreactive cortical efferent axons. (ii) In rats exposed to X-ray irradiation
      at E14, cystic cavities were formed in the cortex-striatum boundary region
      between E15 and E17, probably because of delayed cell death of neurons generated
      at E14. These cavities transiently interrupted both cortical afferent (L1
      positive) and efferent (TAG-1-positive) axons. (iii) X-ray irradiation at E14
      partially destroyed subplate neurons (transient targets of thalamic afferent
      axons) and disturbed the arrangement of the subplate layer. This resulted in a
      misrouting of neurofilament- and L1-immunoreactive thalamocortical axons that
      obliquely traversed the cortical plate to run up to the superficial layer. The
      present study demonstrates for the first time that X-ray irradiation during
      initial cortical development causes multiple defects in the formation of cortical
      afferent and efferent pathways.

PMID- 15869482
TI  - Neurochemical characterization of the cerebellar-recipient motor thalamic
      territory in the macaque monkey.
AB  - Abstract The immunoarchitectonics of the macaque motor thalamus was analysed to
      look for a possible neurochemical characterization of thalamic territories, which
      were not definable cytoarchitectonically, associated with different functional
      pathways. Thalamic sections from 15 macaque monkeys were processed for
      visualization of calbindin (CB), parvalbumin (PV), calretinin (CR) and SMI-32
      immunoreactivity (ir). PV-, CR- and SMI-32ir distributions did not show any clear
      correlation with known functional subdivisions. In contrast, CBir distribution
      reliably defined two markedly distinct motor thalamic territories, one
      characterized by high cell and neuropil CBir (CB-positive territory), the other
      by very low cell and neuropil CBir (CB-negative territory). These two
      neurochemically distinct compartments, the CB-negative and the CB-positive
      territories, appear to correspond to the cerebellar- and basal ganglia-recipient
      territories, respectively. To verify the possible correspondence of the CB
      negative territory with the cerebellar-recipient sector of the motor thalamus, we
      compared the distribution of cerebello-thalamic projections with the distribution
      of CBir in two monkeys. The distribution of cerebellar afferent terminals was
      similar to that reported from previous reports and in line with the notion that
      in the motor thalamus the cerebellar-recipient territory does not respect
      cytoarchitectonic boundaries. Comparison with CB immunoarchitecture showed very
      close correspondence in the motor thalamus between the distribution of the
      anterograde labeling and the CB-negative territory, suggesting that the CB
      negative territory represents the architectonic counterpart of the cerebellar
      recipient territory. CB immunostaining may therefore represent a helpful tool for
      describing the association between thalamocortical projections and the basal
      ganglia or the cerebellar loops and for establishing possible homologies between
      the motor thalamus of non-human primates and humans.

PMID- 15869481
TI  - Connexin26 is responsible for anionic molecule permeability in the cochlea for
      intercellular signalling and metabolic communications.
AB  - Abstract A gap junction is composed of two hemichannels and possesses a
      relatively large pore size ( approximately 10-15 A), allowing passage of ions and
      molecules up to 1 kDa. Here, we report that connexin hemichannels and gap
      junctions in the guinea pig cochlea had significant charge selectivity among
      permeating molecules. In coincubation with anionic and cationic fluorescent dyes,
      hemichannel permeability in isolated cochlear supporting cells showed significant
      charge selectivity; 31% of cells had only cationic dye influx and 6% of cells had
      only anionic dye influx. Charge-selective influx contrary to dye size was also
      found, indicating charge as a dominant determinant in permeability. The cell-cell
      gap junctional permeability was consistent with hemichannel permeability and also
      showed strong charge selectivity; the permeation of anionic dyes was slower than
      that of cationic probes in the cochlear sensory epithelium. With a combination of
      immunofluorescent staining for connexin26 (Cx26) and Cx30, which are the
      predominant connexin isoforms in the cochlea, Cx26 was demonstrated to correlate
      with anionic permeability. The data indicated that cochlear gap junctions have
      strong charge selectivity in molecular permeability and metabolic communication.
      Cx26 mutation may induce specific, irreparable impairment in intercellular
      signalling and energy and nutrient supplies in the cochlea, causing cell
      degeneration and hearing loss, given that many important cell-signalling and
      nutrient and energy molecules (e.g. IP3, ATP, cAMP and cGMP) are anions.

PMID- 15869483
TI  - Forebrain projections to the hypothalamus are topographically organized in
      anurans: conservative traits as compared with amniotes.
AB  - The organization of the forebrain in amphibians (anamniotes) is currently being
      re-evaluated in terms of evolution and several evidences have corroborated
      numerous traits shared by amphibians and amniotes, such as the organization of
      the basal ganglia and the amygdaloid complex. In the present study we have
      analysed the organization of forebrain afferent systems to the hypothalamus of
      the frog Rana perezi. In vivo and in vitro tract-tracing techniques with dextran
      amines and immunohistochemistry for localizing nitric oxide synthase (NOS) in a
      series of single or combined experiments were used as NOS labelling reveals
      hypothalamic afferents arising from the lateral amygdala and the combination
      allowed analysis of the relationship between fibers of different origins in the
      same section. The results showed a large segregation of afferents in the
      hypothalamic region depending on their site of origin in the forebrain. Four
      highly topographically organized prosencephalic tracts reaching the anuran
      hypothalamus were observed: (i) the medial forebrain bundle, from the medial
      pallium and septal complex; (ii) the caudal branch of the stria terminalis formed
      by fibers arising in the lateral and medial amygdala; (iii) part of the lateral
      forebrain bundle with fibers from the central amygdala and (iv) the dorsal
      thalamo-hypothalamic tract. Fibers coursing in each tract reach the hypothalamus
      and terminate in distinct fields. The resemblance in pattern of forebrain
      hypothalamic organization between amphibians and amniotes suggests that this
      feature represents an important trait conserved in the evolution of all tetrapods
      and therefore essential for the hypothalamic function.

PMID- 15869484
TI  - Increased osteopontin expression following intranigral lipopolysaccharide
      injection in the rat.
AB  - Nigral cell death in Parkinson's disease is characterized by glial cell
      activation leading to inflammatory changes. Osteopontin (OPN) is a glycosylated
      phosphoprotein that is induced by inflammatory mediators and which we have
      previously shown to be present in the substantia nigra. However, the role of OPN
      in the nigral inflammation is not known. We now report on the effects of
      lipopolysaccharide (LPS)-induced glial cell activation in the substantia nigra of
      rats on OPN expression. LPS administration induced dopaminergic cell death as
      shown by reduced nigral tyrosine hydroxylase immunoreactivity. There was a
      corresponding time-dependent increase in both OPN mRNA, which was maximal at 48
      h, and protein levels, which peaked at 72 h before returning to control levels by
      120 h. This increase was accompanied by marked reactive gliosis as shown by
      increased OX-42, glial fibrillary acidic protein (GFAP) and ED1 immunoreactivity.
      OX-42-positive cells increased in a time-dependent manner, peaking at 72 h before
      returning to control levels at 120 h. Similarly, ED1-positive cells were present
      in their greatest numbers at 24 h but then gradually declined. These changes
      mirrored the alterations occurring in OPN protein and OPN mRNA, respectively. In
      contrast, GFAP-positive cells only started to increase in number at 120 h.
      Colocalization studies showed that OPN was present in both ED1- and OX-42
      positive cells but not in GFAP-positive cells. These data confirm that
      intranigral injection of LPS induces a rapid and marked gliosis that accompanies
      the loss of tyrosine hydroxylase-positive neurones and suggest that, after glial
      cell activation, enhanced expression of OPN occurs linked to increased numbers of
      microglia and/or macrophages. This suggests that OPN may be functionally
      important in the control of inflammatory changes.

PMID- 15869485
TI  - Central nucleus of amygdala projections to rostral ventrolateral medulla neurones
      activated by decreased blood pressure.
AB  - The central nucleus of amygdala (CeA) participates in cardiovascular regulation
      during emotional behaviour but it has not been established whether any of these
      effects are mediated through its direct connections to blood pressure-regulating
      neurones in the rostral ventrolateral medulla (RVLM). The RVLM contains
      barosensitive neurones that maintain resting blood pressure via their projections
      to sympathetic preganglionic neurones in the thoracic spinal cord. In this study
      on rats, we used combined anterograde neuronal tracing of CeA projections with
      confocal and electron microscopic immunohistochemical detection of
      phenylethanolamine-N-methyltransferase, the adrenaline-synthesizing enzyme
      present in C1 catecholamine neurones of the RVLM, and Fos, the protein product of
      the c-fos proto-oncogene. Fos expression in barosensitive neurones was stimulated
      by an intravenous infusion of the hypotensive agent sodium nitroprusside.
      Injection of the tracer biotin dextran amine (10-kDa form) into the CeA resulted
      in anterograde labelling of axons and varicosities throughout the RVLM without
      retrograde labelling of somata in any brain area. With confocal microscopy,
      presumptive CeA terminals were found in close apposition to adrenergic
      (phenylethanolamine-N-methyltransferase-immunoreactive) and non-adrenergic
      neurones that displayed Fos-immunoreactive nuclei in response to decreased blood
      pressure. Electron microscopic analysis confirmed that some labelled terminals of
      CeA axons made synaptic contact with c-fos-activated adrenergic neurones. The
      results provide evidence that cardiovascular influences elicited from the CeA
      during stressful events may be mediated, at least in part, via monosynaptic
      neural projections to barosensitive sympathetic blood pressure-regulating
      neurones in the RVLM.

PMID- 15869486
TI  - Arousal and differential Fos expression in histaminergic neurons of the ascending
      arousal system during a feeding-related motivated behaviour.
AB  - Arousal depends on the concerted activity of the ascending arousal system (AAS)
      but specific stimuli may primarily activate some nuclei of this system. Motivated
      behaviours are characterized by behavioural arousal, although it is not known
      which AAS nuclei are active during a motivated behaviour. To address this issue,
      rats were rendered motivated for food by fasting them for 1 day and then were
      enticed with food that they could not obtain for varying periods of time. We
      studied the level of arousal by polysomnography or radiotelemetry, and Fos-ir in
      the AAS, during food enticing. We found a strong arousal and an early increase in
      Fos-ir in the histaminergic neurons from the tuberomammillary nucleus, after 30
      min of enticing, followed by increased Fos-ir in the whole AAS if food enticing
      was prolonged to 1 or 2 hours. In contrast, food presentation to non-motivated
      rats did not increase arousal or Fos-ir in the tuberomammillary nucleus. As
      opposed to the active arousal of the motivated rats, passive arousal induced by
      sensory stimulation was associated with increased Fos-ir in the locus coeruleus
      and the orexin neurons, but not with increased Fos-ir in the tuberomammillary
      nucleus or in the other nuclei of the AAS. We conclude that the arousal during
      feeding-related motivated behaviour is associated primarily with the activation
      of the tuberomammillary nucleus, while the other arousal-related nuclei become
      active later on.

PMID- 15869487
TI  - Opposite effects of tetanic stimulation of the auditory thalamus or auditory
      cortex on the acoustic startle reflex in awake rats.
AB  - The amygdala mediates both emotional learning and fear potentiation of startle.
      The lateral amygdala nucleus (LA) receives auditory inputs from both the auditory
      thalamus (medial geniculate nucleus; MGN) and auditory association cortex (AAC),
      and is critical for auditory fear conditioning. The central amygdala nucleus,
      which has intra-amygdaloid connections with LA, enhances startle magnitude via
      midbrain connections to the startle circuits. Tetanic stimulation of either MGN
      or AAC in vitro or in vivo can induce long-term potentiation in LA. In the
      present study, behavioural consequences of tetanization of these auditory
      afferents were investigated in awake rats. The acoustic startle reflex of rats
      was enhanced by tetanic stimulation of MGN, but suppressed by that of AAC. All
      the tetanization-induced changes of startle diminished within 24 h. Blockade of
      GABAB receptors in the LA area reversed the suppressive effect of tetanic
      stimulation of AAC on startle but did not change the enhancing effect of tetanic
      stimulation of MGN. Moreover, transient electrical stimulation of MGN enhanced
      the acoustic startle reflex when it lagged behind acoustic stimulation, but
      inhibited the acoustic startle reflex when it preceded acoustic stimulation. The
      results of the present study indicate that MGN and AAC afferents to LA play
      different roles in emotional modulation of startle, and AAC afferents are more
      influenced by inhibitory GABAB transmission in LA.

PMID- 15869488
TI  - The dependence of the auditory evoked N1m decrement on the bandwidth of preceding
      notch-filtered noise.
AB  - The auditory evoked response is known to be changed by a preceding sound. In this
      study we investigated by means of magnetoencephalography how a preceding notch
      filtered noise (NFN) with different bandwidths influences the human auditory
      evoked response elicited by the following test stimulus. We prepared white noise
      (WN) and four NFNs which were derived from WN by suppressing frequency regions
      around 1 kHz with 1/8-, 1/4-, 1/2- and 1-octave bandwidths. Stimulation for 3 s
      with this set of noises resulted in differences in responsiveness to a 1-kHz test
      tone presented 500 ms after the offset of the noises. The N1m response to the 1
      kHz test tone stimulus was at a minimum when the preceding NFN had 1/4-octave
      stop-band frequencies as compared with 1/8-, 1/2- and 1-octave NFN and WN. This
      N1m decrement is explained by the imbalanced neural activities caused by
      habituation and lateral inhibition in the auditory system. The results contribute
      to understanding of the inhibitory system in the human auditory cortex.

PMID- 15869489
TI  - A role for norepinephrine in the regulation of context-dependent ZENK expression
      in male zebra finches (Taeniopygia guttata).
AB  - Singing drives expression of the immediate-early gene ZENK in a context-dependent
      manner in certain nuclei within the avian song circuit of male zebra finches
      (Taeniopygia guttata). ZENK mRNA expression is low when males are engaged in
      female- or male-directed song, but high during solo song. Neurotransmitter
      systems like catecholamines with diffuse projections to forebrain regions are
      good candidates for regulation of such context-dependent brain activity. We
      investigated whether the noradrenergic system regulates the dramatic switch in
      ZENK expression across contexts in male zebra finches. We systemically injected a
      noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine
      hydrochloride (DSP-4) and found a marked increase in the resultant ZENK
      expression in area X of the medial striatum in male zebra finches singing
      directed song. ZENK protein expression in saline-treated males across different
      contexts mirrored the pattern of previously reported ZENK mRNA expression. We
      corroborated DSP-4 specificity via immunohistochemical procedures for tyrosine
      hydroxylase and dopamine-beta hydroxylase, which revealed decreases in
      norepinephrine synthesizing nuclei and certain song control nuclei. Based on
      these results we propose a mechanism by which the noradrenergic system usually
      downregulates ZENK expression in area X during directed song. By depleting this
      system we induced a disruption of this regulation and reversion back to the
      default situation characterized by an increase in motor-driven ZENK expression in
      the song circuit. These data demonstrate that the noradrenergic system (probably
      in concert with other modulatory neurotransmitters) plays an important role in
      the response of the brain to salient events that occur in the context of a
      natural behavior--singing.

PMID- 15869490
TI  - Selective effects of partial striatal 6-OHDA lesions on information processing in
      the rat.
AB  - The present study was aimed at characterizing the cognitive deficits caused by
      the degeneration of nigrostriatal dopamine (DA) pathways by using the additive
      factor logic [Sternberg, S. (1969) Acta Psychol., 30, 276-315], a powerful
      reaction time (RT) method developed in humans and recently introduced in the rat
      [Courtiere, A., Hardouin, J., Hasbroucq, T., Possamai, C.-A. & Vidal, F. (2000)
      Behav. Process., 50, 113-121]. Long-Evans rats were trained to respond to left or
      right (lateral) visual cues in a choice RT task. Two task factors, signal
      intensity and force requirement, were manipulated. Partial bilateral 6-OHDA
      lesions of DA nerve terminals in the striatum were then performed and their
      effects tested for up to 7 weeks following surgery. Reaction time was lengthened
      from the 2nd to the 4th week postlesion. This alteration was independent of force
      requirement, thereby suggesting that the related motor processes were not
      influenced by the DA depletion. During the 2nd week postlesion, the RT increase
      was accompanied by a disappearance of the effect of signal intensity, showing
      that the lesion altered stimulus-related processes. From the 3rd week the signal
      intensity effect was re-established although RT was still increased, indicating
      that the stimulus-related processes had recovered while other central processes
      were still impaired. From the 5th week after surgery, the lesioned animals had
      completely recovered from the RT deficits induced by the lesion. These results
      point at the involvement of striatal DA in sensory and central information
      processes.

PMID- 15869491
TI  - Cocaine dependence and attention switching within and between verbal and
      visuospatial working memory.
AB  - Many studies have shown the negative effects of cocaine on neuropsychological and
      cognitive performance in drug-dependent individuals, but little is known about
      the underlying neuroanatomy of these dysfunctions. The present study addressed
      attention switching between items held in working memory (WM) with a task in
      which subjects were required to store and update two items held in verbal or
      visuospatial WM. Attention-switching frequency varied between trials, thereby
      allowing us to isolate the switching component of task performance. Behavioural
      data revealed that cocaine addicts performed worse than healthy controls in all
      tasks. On the visuospatial task addicts performed at chance levels revealing
      particular impairment in visuospatial WM. On the verbal task, in which controls
      and users could be matched for performance, we identified attenuated responses in
      prefrontal and cingulate cortices and in striatal regions, while other areas such
      as dorsolateral prefrontal cortex did not differ between healthy controls and
      users. The results reveal that addiction may be accompanied by specific rather
      than ubiquitous hypoactivation in prefrontal and subcortical areas and suggest a
      compromised ability in users to control their attention to their thoughts as
      might be particularly relevant when required to switch away from drug-related
      thoughts, and thus the dysfunction in attention switching may contribute to the
      maintenance of addiction.

PMID- 15869492
TI  - Recapitulating emotional context: activity of amygdala, hippocampus and fusiform
      cortex during recollection and familiarity.
AB  - The amygdala is thought to enhance long-term memory for emotionally arousing
      events by modulating memory formation and storage in the hippocampus and in
      neocortical areas. Recent animal studies have raised the possibility that
      cooperativity between amygdala and hippocampus contributes to the retrieval of
      fear memories. The functional contributions of the amygdala to the retrieval of
      emotional memories in humans are less well known. Here, in a functional magnetic
      resonance imaging experiment, 20 healthy subjects studied neutral words in the
      context of a fearful or a neutral human face. In a subsequent test, they made
      'remember' (conscious recollection of the study context), 'know' (familiarity in
      the absence of conscious recollection) and 'new' judgements on the studied and
      newly presented neutral words, in the absence of face stimuli. At test, bilateral
      amygdala, hippocampus and fusiform face area (FFA) were more strongly activated
      during recollection than during familiarity. Higher activity for fearful than for
      neutral study context was found in bilateral FFA during recollection but not
      during familiarity. This difference recapitulated higher activity for fearful
      than for neutral context in the FFA during study. These data suggest that the
      amygdalae and hippocampi contribute to the retrieval of emotion-laden context
      memories by coordinating the reactivation of stored representations in
      neocortical areas, such as the FFA. However, there also was a recapitulation of
      emotional study context in the right amygdala during familiarity only, which
      might therefore be related to affective implicit memory.

PMID- 15869493
TI  - Right-hemisphere motor facilitation by self-descriptive personality-trait words.
AB  - The emergent picture from the literature on the processing of self-related
      information suggests that in addition to the neural mechanisms involved in
      recognizing one's own face, there may also be neural representations of the self
      that are modality independent and favour the right hemisphere. We used focal,
      single-pulse transcranial magnetic stimulation in human subjects to assess
      cortical excitability during covert reading of self-descriptive personality-trait
      words. We hypothesized that the right hemisphere would show a greater overall
      facilitation to personality-trait words than the left hemisphere. Overall,
      personality-trait words led to significantly greater motor facilitation in the
      right hemisphere than in the left hemisphere. In addition, words rated as 'never'
      self-characteristic yielded significant right hemisphere facilitation, and words
      rated as 'always' self-characteristic showed a similar trend. The results are
      discussed in terms of the notion that the right hemisphere plays a dominant role
      in both self-relevant processing and the processing of affective stimuli.

PMID- 15869494
TI  - Rapid categorization of achromatic natural scenes: how robust at very low
      contrasts?
AB  - The human visual system is remarkably good at categorizing objects even in
      challenging visual conditions. Here we specifically assessed the robustness of
      the visual system in the face of large contrast variations in a high-level
      categorization task using natural images. Human subjects performed a go/no-go
      animal/nonanimal categorization task with briefly flashed grey level images.
      Performance was analysed for a large range of contrast conditions randomly
      presented to the subjects and varying from normal to 3% of initial contrast.
      Accuracy was very robust and subjects were performing well above chance level
      (approximately 70% correct) with only 10-12% of initial contrast. Accuracy
      decreased with contrast reduction but reached chance level only in the most
      extreme condition (3% of initial contrast). Conversely, the maximal increase in
      mean reaction time was approximately 60 ms (at 8% of initial contrast); it then
      remained stable with further contrast reductions. Associated ERPs recorded on
      correct target and distractor trials showed a clear differential effect whose
      amplitude and peak latency were correlated respectively with task accuracy and
      mean reaction times. These data show the strong robustness of the visual system
      in object categorization at very low contrast. They suggest that magnocellular
      information could play a role in ventral stream visual functions such as object
      recognition. Performance may rely on early object representations which lack the
      details provided subsequently by the parvocellular system but contain enough
      information to reach decision in the categorization task.

PMID- 15869495
TI  - Development of pontine noradrenergic A5 neurons requires brain-derived
      neurotrophic factor.
AB  - Pontine noradrenergic A5 neurons play a pivotal role in maturation and regulation
      of the brainstem respiratory rhythm-generating network. Analysis of newborn brain
      derived neurotrophic factor (BDNF)-null mice revealed a marked loss of tyrosine
      hydroxylase-positive A5 neurons compared to wildtype controls that was rescued by
      null mutation of the proapoptotic gene Bax. In cultures of the A5 region from
      E12.5 rat embryos, BDNF significantly increased the number and branching of
      tyrosine hydroxylase-positive neurons. Immunoneutralization of endogenous glial
      cell line-derived neurotrophic factor partially inhibited the BDNF-dependent
      increase in the number of tyrosine hydroxylase-positive cells without affecting
      neurite number. The A5 nucleus is the first brainstem cell group identified at
      which BDNF is required in vivo for development of neurons critical for
      cardiorespiratory control.

PMID- 15869496
TI  - Adult motor neurons show increased susceptibility to axotomy-induced death in
      mice lacking clusterin.
AB  - Clusterin is a highly conserved, amphiphatic glycoprotein present in most
      tissues. It has been shown to be involved in the regulation of lipid
      transportation, clearance of cellular debris from the extracellular space and
      intracellular signal transduction. Clusterin is markedly up-regulated after
      neural injury but the functional significance of this response is unclear. Here,
      we show that clusterin up-regulation is substantially greater in hypoglossal
      motor neurons after hypoglossal nerve avulsion compared with nerve transection.
      Quantitative analyses of motor neuron numbers after the same lesions in
      clusterin(-/-) and clusterin(+/+) mice showed significantly larger numbers of
      surviving motor neurons in clusterin(+/+) mice. These results suggest that
      clusterin has a neuroprotective role after axotomy.

PMID- 15869497
TI  - Lens injury stimulates adult mouse retinal ganglion cell axon regeneration via
      both macrophage- and lens-derived factors.
AB  - In the present study the effects of lens injury on retinal ganglion cell
      axon/neurite re-growth were investigated in adult mice. In vivo, lens injury
      promoted successful regeneration of retinal ganglion cell axons past the optic
      nerve lesion site, concomitant with the invasion of macrophages into the eye and
      the presence of activated retinal astrocytes/Muller cells. In vitro, retinal
      ganglion cells from lens-lesioned mice grew significantly longer neurites than
      those from intact mice, which correlated with the presence of enhanced numbers of
      activated retinal astrocytes/Muller cells. Co-culture of retinal ganglion cells
      from intact mice with macrophage-rich lesioned lens/vitreous body led to
      increased neurite lengths compared with co-culture with macrophage-free intact
      lens/vitreous body, pointing to a neurotrophic effect of macrophages.
      Furthermore, retinal ganglion cells from mice that had no lens injury but had
      received intravitreal Zymosan injections to stimulate macrophage invasion into
      the eye grew significantly longer neurites compared with controls, as did retinal
      ganglion cells from intact mice co-cultured with macrophage-rich vitreous body
      from Zymosan-treated mice. The intact lens, but not the intact vitreous body,
      exerted a neurotrophic effect on retinal ganglion cell neurite outgrowth,
      suggesting that lens-derived neurotrophic factor(s) conspire with those derived
      from macrophages in lens injury-stimulated axon regeneration. Together, these
      results show that lens injury promotes retinal ganglion cell axon
      regeneration/neurite outgrowth in adult mice, an observation with important
      implications for axon regeneration studies in transgenic mouse models.

PMID- 15869498
TI  - Effects of cocaine-induced behavioural sensitization on GABA transmission within
      rat medial prefrontal cortex.
AB  - Studies support the involvement of mPFC dopaminergic and glutamatergic systems in
      the development of cocaine sensitization. GABA is known to modulate dopamine and
      glutamatergic systems in the mPFC. In addition, recent reports have suggested
      that cocaine sensitization might be associated with a decrease in GABAB receptor
      responsiveness in the mPFC. Hence, in vivo microdialysis of the mPFC was
      performed to examine the effects on extracellular GABA levels within the mPFC of
      a cocaine challenge subsequent to repeated cocaine administration. Male Sprague
      Dawley rats were given four daily injections of saline (1.0 mL/kg, i.p.) or
      cocaine (15 mg/kg, i.p.) and challenged with the same dose of saline or cocaine
      1, 7 or 28 days later. Acute cocaine produced a motor-stimulant response that was
      significantly augmented in repeated cocaine animals at all withdrawal time
      points. Moreover, sensitized animals exhibited a significant increase in
      extracellular GABA levels after 1 and 7 days but not 28 days following repeated
      cocaine exposure. These data suggest that cocaine-induced sensitization is
      associated with a transient increase in mPFC GABA transmission.

PMID- 15869499
TI  - Binding of motion and colour is early and automatic.
AB  - At what stages of the human visual hierarchy different features are bound
      together, and whether this binding requires attention, is still highly debated.
      We used a colour-contingent motion after-effect (CCMAE) to study the binding of
      colour and motion signals. The logic of our approach was as follows: if CCMAEs
      can be evoked by targeted adaptation of early motion processing stages, without
      allowing for feedback from higher motion integration stages, then this would
      support our hypothesis that colour and motion are bound automatically on the
      basis of spatiotemporally local information. Our results show for the first time
      that CCMAE's can be evoked by adaptation to a locally paired opposite-motion dot
      display, a stimulus that, importantly, is known to trigger direction-specific
      responses in the primary visual cortex yet results in strong inhibition of the
      directional responses in area MT of macaques as well as in area MT+ in humans
      and, indeed, is perceived only as motionless flicker. The magnitude of the CCMAE
      in the locally paired condition was not significantly different from control
      conditions where the different directions were spatiotemporally separated (i.e.
      not locally paired) and therefore perceived as two moving fields. These findings
      provide evidence that adaptation at an early, local motion stage, and only
      adaptation at this stage, underlies this CCMAE, which in turn implies that
      spatiotemporally coincident colour and motion signals are bound automatically,
      most probably as early as cortical area V1, even when the association between
      colour and motion is perceptually inaccessible.

PMID- 15869500
TI  - Long-term potentiation of human visual evoked responses.
AB  - Long-term potentiation (LTP) is a candidate synaptic mechanism underlying
      learning and memory that has been studied extensively at the cellular and
      molecular level in laboratory animals. To date, LTP has only been directly
      demonstrated in humans in isolated cortical tissue obtained from patients
      undergoing surgery, where it displays properties identical to those seen in non
      human preparations. Inquiry into the functional significance of LTP has been
      hindered by the absence of a human model. Here we give the first demonstration
      that the rapid repetitive presentation of a visual checkerboard (a photic
      'tetanus') leads to a persistent enhancement of one of the early components of
      the visual evoked potential in normal humans. The potentiated response is largest
      in the hemisphere contralateral to the tetanized visual hemifield and is limited
      to one component of the visual evoked response (the N1b). The selective
      potentiation of only the N1b component makes overall brain excitability changes
      unlikely and suggests that the effect is due instead to an LTP process. While LTP
      is known to exist in the human brain, the ability to elicit LTP from non-surgical
      patients will provide a human model system allowing the detailed examination of
      synaptic plasticity in normal subjects and may have future clinical applications
      in the assessment of cognitive disorders.

PMID- 15869501
TI  - The ability of axons to regenerate their growth cones depends on axonal type and
      age, and is regulated by calcium, cAMP and ERK.
AB  - The processes activated at the time of axotomy and leading to the formation of a
      new growth cone are the first step in regeneration, but are still poorly
      characterized. We investigated this event in an in vitro model of axotomy
      performed on dorsal root ganglia and retinal explants. We observed that the
      dorsal root ganglion axons and retinal ganglion cell axons, which had grown out
      on a poly d-lysine/laminin substrate at the time of culture preparation greatly
      differed in their regenerative response after a subsequent in vitro lesion made
      far from the cell body. The majority of axons of adult dorsal root ganglia but
      only a small percentage of axons of adult retinal ganglion cells regenerated new
      growth cones within four hours after in vitro axotomy, though both kinds of axons
      were growing before the lesion. The depletion of extracellular calcium and the
      inhibition of extracellular-signal regulated kinase 1,2 (ERK) and protein kinase
      A (PKA) at the time of injury significantly impaired the capacity of dorsal root
      ganglia axons to re-initiate growth cones without affecting growth cone motility.
      Pharmacological treatments directed at increasing the level of cAMP promoted
      growth cone regeneration in adult retinal ganglion cell axons in spite of the low
      regenerative potential exhibited in normal conditions. Understanding the cellular
      mechanisms activated at the time of lesion and leading to the formation of a new
      growth cone is necessary for devising treatments aimed at enhancing the
      regenerative response of injured axons.

PMID- 15869502
TI  - The scrapie prion protein is present in flotillin-1-positive vesicles in central-
      but not peripheral-derived neuronal cell lines.
AB  - Abstract Transmissible prion diseases are fatal neurodegenerative diseases
      associated with the conversion of the normal host prion protein (PrP c) into an
      abnormal isoform (PrP Sc) that accumulates in brain. This pathology affects
      neurons of the central nervous system whereas no clear toxic effect has been
      reported for peripheral neurons. We examined the subcellular distribution of PrP
      c and PrP Sc in the scrapie-infected mouse neuronal cell lines GT1-7 and N2a,
      derived, respectively, from the central and peripheral nervous system. We
      observed that in both cell types, PrP c is present in the endocytic compartment,
      mainly in LAMP-1-positive late endosomes, but excluded from LYAAT-1-lysosomes. In
      contrast, PrP Sc was distributed differently in the two cell lines. In infected
      N2a, PrP Sc and PrP c had comparable distribution patterns. In infected GT1-7,
      PrP Sc is present in an additional vesicular compartment which is flotillin-1
      positive. The level of expression of flotillin-1 is higher in GT1-7 than in N2a
      cells, but no difference is observed between infected and noninfected cells. In
      Alzheimer's disease patients, it has been reported that flotillin-1 is abundant
      in brain areas containing the beta-amyloid protein, which accumulates in
      endosomal vesicles in primary neurons. We propose that the flotillin compartment
      could store aggregated proteins and play a role in these neurodegenerative
      pathologies.

PMID- 15869503
TI  - Preferential localization of the hyperpolarization-activated cyclic nucleotide
      gated cation channel subunit HCN1 in basket cell terminals of the rat cerebellum.
AB  - Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels are
      involved in the control of neuronal excitability and plasticity. In this study,
      we used immunoblotting and immunohistochemical techniques to reveal the
      developmental expression and subcellular distribution of the HCN1 subunit in the
      cerebellar cortex. During postnatal development, the spatio-temporal expression
      of HCN1 correlated well with the morphological events occurring during the
      ontogenesis of cerebellar interneurons. Using immunoblotting techniques, HCN1 was
      weakly detected during the first postnatal week and continued to increase
      throughout postnatal development, peaking at postnatal day (P)15. At the light
      microscopic level, HCN1 immunoreactivity was very weak until P7 whereas from P10
      12 to adulthood it was strongly detected in the lower third of the molecular
      layer and in the Purkinje cell layer. HCN1 was present in axons running through
      the molecular layer and in the pericellular basket around Purkinje cells at P12,
      but in the periaxonal plexus (the pinceau) surrounding their initial segment only
      after P15. Using immunofluorescence, HCN1 colocalized with GAD65 and
      synaptophysin, demonstrating that the subunit was present in inhibitory axons and
      axon terminals. At the electron-microscopic level, in adulthood, HCN1
      immunoparticles were detected at postsynaptic sites in basket and Purkinje cells
      but most immunoparticles were found at presynaptic sites in basket cell axons and
      in terminals. In the axon terminals, the distribution of HCN1 was relatively
      uniform along the extrasynaptic plasma membrane; this was confirmed using
      quantitative techniques. The present findings suggest that HCN1 channels may
      provide a significant route for modulating co-ordinated cerebellar synaptic
      transmission through basket cells.

PMID- 15869504
TI  - Rapid non-genomic effect of glucocorticoid metabolites and neurosteroids on the
      gamma-aminobutyric acid-A receptor.
AB  - Glucocorticoids and neurosteroids, such as allopregnanolone and
      tetrahydrodeoxycorticosterone, are released during stress. A non-genomic effect
      of glucocorticoids has been established but is not yet fully understood. We have
      studied the effect of glucocorticoid metabolites on the gamma-aminobutyric acid
      (GABA) system. In these experiments we studied the effects of the glucocorticoid
      metabolites allotetrahydrocortisol, tetrahydrocortisol, allotetrahydrocortisone
      and tetrahydrocortisone in rat cortical microsacs. Our results showed that both
      these cortisol and cortisone metabolites reduce GABA-mediated chloride ion
      uptake. This reduction was not observed in the presence of allopregnanolone but
      allotetrahydrocortisol interacts with allopregnanolone, enhancing the
      allopregnanolone-stimulated potentiation of GABA-mediated chloride ion uptake.
      This enhanced effect was completely blocked by the addition of 30 microm of the
      3beta-isomer of allopregnanolone, isoallopregnanolone. Our findings show that
      steroids released during stress interact with each other and GABA in the GABA
      system.

PMID- 15869505
TI  - Estrogen induces a rapid increase in galanin levels in female rat hippocampal
      formation--possibly a nongenomic/indirect effect.
AB  - Administration of 17beta-estradiol to ovariectomized rats increased the
      concentrations of galanin-like immunoreactivity (LI) in the hippocampal formation
      by 215% (P < 0.001) within 1 h. An increase of 125% (P < 0.05) was observed in
      the same brain region in the proestrous phase of a normal estrous cycle.
      Tamoxifen did not block the 17beta-estradiol-induced increase in the
      concentration of galanin-LI but resulted in a 62% decrease in the hypothalamus
      within 1 h. In vivo microdialysis in the dorsal hippocampal formation showed a
      decrease of extracellular galanin-LI (P < 0.001) 1-2 h after treatment with
      17beta-estradiol, indicating a decreased release of galanin. For comparison, we
      studied the concentrations of neuropeptide Y, which were not influenced
      significantly in any of the regions studied. Taken together our results suggest
      that 17beta-estradiol inhibits galanin release, presumably from noradrenergic
      nerve terminals, and primarily via a nongenomic/indirect action, not necessarily
      involving the classical nuclear receptors ER-alpha or ER-beta. These rapid
      estrogen-induced changes in galanin release could influence transmitter
      signalling and plasticity in the hippocampal formation.

PMID- 15869506
TI  - Neurotrophin-3 null mutant mice display a postnatal motor neuropathy.
AB  - This paper examines early postnatal development of the neuromuscular system in
      mice with a null mutation in the gene for neurotrophin-3. We report that alpha
      motoneurons at first develop substantially normally, despite a known 15% deficit
      in their somal size [Woolley et al. (1999)Neurosci. Lett., 272, 107-110.] and the
      absence of proprioceptive input [Ernfors et al. (1994)Cell, 77, 503-512]. At
      birth, motor axons have extended into the muscle, forming normal-looking
      neuromuscular junctions with focal accumulations of acetylcholine receptors.
      Detailed ultrastructural analysis does however, reveal subtle abnormalities at
      this time, particularly a decrease in the extent of occupancy of the postsynaptic
      site by nerve terminals, and a small but significant deficit in myofibre number.
      After the relative normality of this early neuromuscular development, there then
      occurs a catastrophic postnatal loss of motor nerve terminals, resulting in
      complete denervation of hindlimb muscles by P7. In systematic semi-serial samples
      through the entire muscle endplate zones, no neuromuscular junctions can be
      found. Intramuscular axons are fragmented, as shown by both electron microscopic
      observations and neurofilament immunohistochemistry, and alpha-bungarotoxin
      detection of acetylcholine receptors indicates dispersal of the junctional
      accumulation. At earlier times (postnatal days three and four) the terminal
      Schwann cells show ultrastructural abnormalities, and preliminary observations
      suggest marked disturbance of myelination. Based on comparison with other
      literature, the peripheral nerve degeneration seems unlikely to have arisen as a
      secondary effect of de-afferentation. We discuss whether the neural degeneration
      is secondary to the disturbance of Schwann cell function, or due directly to a
      loss of neurotrophin-3 based support of the motoneuron.

PMID- 15869507
TI  - Glutamatergic innervation of neuropeptide Y and pro-opiomelanocortin-containing
      neurons in the hypothalamic arcuate nucleus of the rat.
AB  - Abstract The hypothalamic arcuate nucleus contains a number of neurochemically
      different cell populations, among others neuropeptide Y (NPY)- and pro
      opiomelanocortin (POMC)-derived peptide-expressing neurons; both are involved in
      the regulation of feeding and energy homeostasis, NPY neurons also in the release
      of hypophysiotropic hormones, sexual behaviour and thermogenesis. Recent
      observations indicate that there is a dense plexus of glutamatergic fibres in the
      arcuate nucleus. The aim of the present studies was to examine the relationship
      of these fibres to the NPY and POMC neurons in the arcuate nucleus. Double-label
      immunoelectron microscopy was used. Glutamatergic elements were identified by the
      presence of vesicular glutamate transporter 1 (VGluT1) or 2 (VGluT2) (selective
      markers of glutamatergic elements) immunoreactivity. A significant number of
      VGluT2-immunoreactive terminals was observed to make asymmetric type of synapses
      with NPY and with beta-endorphin (a marker of POMC neurons)-immunostained nerve
      cells of the arcuate nucleus. About 15% of VGluT2 synapsing terminals established
      asymmetric synapses with NPY-positive cells and more than 40% of VGlut2-positive
      terminals formed synapse on beta-endorphin-positive neurons. VGluT2-positive
      perikarya were also observed, part of them also contained beta-endorphin. Nerve
      terminals containing both VGluT2 and beta-endorphin were demonstrated in the cell
      group. Only very few VGluT1 fibres were detected. Our observations provide the
      first direct neuromorphological evidence for the existence of glutamatergic
      innervation of NPY and POMC neurons of the arcuate nucleus.

PMID- 15869508
TI  - Presence of vesicular glutamate transporter-2 in hypophysiotropic somatostatin
      but not growth hormone-releasing hormone neurons of the male rat.
AB  - Recent evidence indicates that hypophysiotropic gonadotropin-releasing hormone
      (GnRH), corticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone
      (TRH) neurons of the adult male rat express mRNA and immunoreactivity for type-2
      vesicular glutamate transporter (VGLUT2), a marker for glutamatergic neuronal
      phenotype. In the present study, we investigated the issue of whether these
      glutamatergic features are shared by growth hormone-releasing hormone (GHRH)
      neurons of the hypothalamic arcuate nucleus (ARH) and somatostatin (SS) neurons
      of the anterior periventricular nucleus (PVa), the two parvicellular
      neurosecretory systems that regulate anterior pituitary somatotrophs. Dual-label
      in situ hybridization studies revealed relatively few cells that expressed VGLUT2
      mRNA in the ARH; the GHRH neurons were devoid of VGLUT2 hybridization signal. In
      contrast, VGLUT2 mRNA was expressed abundantly in the PVa; virtually all (97.5 +/
      0.4%) SS neurons showed labelling for VGLUT2 mRNA. In accordance with these
      hybridization results, dual-label immunofluorescent studies followed by confocal
      laser microscopic analysis of the median eminence established the absence of
      VGLUT2 immunoreactivity in GHRH terminals and its presence in many neurosecretory
      SS terminals. The GHRH terminals, in turn, were immunoreactive for the vesicular
      gamma-aminobutyric acid (GABA) transporter, used in these studies as a marker for
      GABA-ergic neuronal phenotype. Together, these results suggest the paradoxic
      cosecretion of the excitatory amino acid neurotransmitter glutamate with the
      inhibitory peptide SS and the cosecretion of the inhibitory amino acid
      neurotransmitter GABA with the stimulatory peptide GHRH. The mechanisms of action
      of intrinsic amino acids in hypophysiotropic neurosecretory systems require
      clarification.

PMID- 15869509
TI  - Pathological implications of iNOS expression in central white matter: an ex vivo
      study of optic nerves from rats with experimental allergic encephalomyelitis.
AB  - Excessive nitric oxide (NO) production from the inducible isoform of nitric oxide
      synthase (iNOS) has been invoked as a causative factor in many neurodegenerative
      disorders, including multiple sclerosis. This hypothesis has been supported by in
      vitro studies showing that glial iNOS expression results in toxic NO
      concentrations (near 1 microm). To investigate the relevance of such findings,
      experiments were carried out ex vivo on optic nerves from rats with exacerbated
      experimental allergic encephalomyelitis, a model of multiple sclerosis. The
      nerves displayed characteristic immunopathology and expression of iNOS in
      macrophages and/or microglia and there was overt axonal damage in localized
      regions of the optic chiasm. The resulting NO levels in the optic nerve were
      sufficient to cause activation of guanylyl cyclase-coupled NO receptors,
      resulting in marked cGMP accumulation in axons throughout the nerve.
      Nevertheless, calibration of cGMP levels against those evoked by exogenous NO
      indicated that the nerves were not compromised metabolically and that their
      ambient NO concentration was only approximately 1 nm. Consistent with this
      observation, electrophysiological tests indicated that there was no ongoing
      malfunctioning of the type that can be elicited by high exogenous NO
      concentrations. It is concluded that, with iNOS expressed in physiological
      locations and levels, the tissue levels of NO remain at concentrations far lower
      than those shown to have toxic effects, despite continuous NO synthesis. The fact
      that NO can rise to much higher levels in dispersed cultures in vitro may be
      attributable to a deficiency in NO inactivation in such preparations.

PMID- 15869510
TI  - Controlling pathological pain by adenovirally driven spinal production of the
      anti-inflammatory cytokine, interleukin-10.
AB  - Gene therapy for the control of pain has, to date, targeted neurons. However,
      recent evidence supports that spinal cord glia are critical to the creation and
      maintenance of pain facilitation through the release of proinflammatory
      cytokines. Because of the ability of interleukin-10 (IL-10) to suppress
      proinflammatory cytokines, we tested whether an adenoviral vector encoding human
      IL-10 (AD-h-IL10) would block and reverse pain facilitation. Three pain models
      were examined, all of which are mediated by spinal pro-inflammatory cytokines.
      Acute intrathecal administration of rat IL-10 protein itself briefly reversed
      chronic constriction injury-induced mechanical allodynia and thermal
      hyperalgesia. The transient reversal caused by IL-10 protein paralleled the half
      life of human IL-10 protein in the intrathecal space (t(1/2) approximately 2 h).
      IL-10 gene therapy both prevented and reversed thermal hyperalgesia and
      mechanical allodynia, without affecting basal responses to thermal or mechanical
      stimuli. Extra-territorial, as well as territorial, pain changes were reversed by
      this treatment. Intrathecal AD-h-IL10 injected over lumbosacral spinal cord led
      to elevated lumbosacral cerebrospinal fluid (CSF) levels of human IL-10, with far
      less human IL-10 observed in cervical CSF. In keeping with IL-10's known anti
      inflammatory actions, AD-h-IL10 lowered CSF levels of IL-1, relative to control
      AD. These studies support that this gene therapy approach provides an alternative
      to neuronally focused drug and gene therapies for clinical pain control.

PMID- 15869511
TI  - Short-term synaptic plasticity during development of rat mossy fibre to granule
      cell synapses.
AB  - Changes occur during the postnatal development of the rat glutamatergic mossy
      fibre to granule cell synapse: to the morphology of synapses, glutamate
      transporter expression, AMPA receptor expression and the kinetics of AMPA
      receptor-mediated synaptic transmission. For example, both the rise and decay
      times of AMPA receptor-mediated excitatory postsynaptic currents significantly
      shorten. To further define the development of mossy fibre to granule cell
      synaptic transmission, the properties and mechanisms of short-term plasticity
      have been described. The characterization of short-term plasticity will aid our
      understanding of the mechanisms that define the parameters of synaptic
      transmission during development and furthermore short-term plasticity may play an
      important role in determining information transfer between mossy fibres and
      granule cells. In response to pairs of stimuli (2-100-ms interval), depression
      (second excitatory postsynaptic current amplitude smaller than the first) was
      observed at both mature (older than 40 postnatal days) and immature (between 8
      and 12 postnatal days) synapses. The degree of depression was similar at both
      stages of development, although recovery from depression was slower at mature
      synapses (tau 22 vs 12.5 ms). Several experimental approaches (coefficient of
      variation, low-affinity antagonists and cyclothiazide) suggest that depression at
      immature synapses results from multiple mechanisms. At mature synapses,
      postsynaptic receptor desensitization appears to be the major cause of
      depression.

PMID- 15869512
TI  - Neurons in the lateral sacral cord of the cat project to periaqueductal grey, but
      not to thalamus.
AB  - Previous work of our laboratory has shown that neurons in the lateral sacral cord
      in cat project heavily to the periaqueductal grey (PAG), in all likelihood
      conveying information from bladder and genital organs. In humans this information
      usually does not reach consciousness, which raises the question of whether the
      lateral sacral cell group projects to the thalamus. After wheatgerm agglutinin
      horseradish peroxidase (WGA-HRP) injections into the sacral cord, anterogradely
      labelled fibers were found in the thalamus, specifically in the ventral anterior
      and ventral lateral nuclei, the medial and intralaminar nuclei, the lateral
      ventrobasal complex/ventroposterior lateral nucleus, and the nucleus centre
      median, lateral to the fasciculus retroflexus. Much denser projections were found
      to the central parts of the PAG, mainly to its dorsolateral and ventrolateral
      parts at caudal levels and lateral parts at intermediate levels. In a subsequent
      retrograde tracing study, injections were made in those parts of the thalamus
      that received sacral fibers, as found in the anterograde study. Labelled neurons
      were observed in the sacral cord, but not in the lateral sacral cell group. In
      contrast, a small control injection in the caudal PAG resulted in many labelled
      neurons in the lateral sacral cord. These results suggest that afferent
      information regarding micturition and sexual behaviour is relayed to the PAG,
      rather than to the thalamus.

PMID- 15869513
TI  - Candidate pheromone receptors of the silkmoth Bombyx mori.
AB  - Communication via specific chemical signals is vitally important for the
      reproductive behaviour of many species. The first identified sex-attractant
      pheromone was bombykol from the silkmoth Bombyx mori. This female-released
      signalling compound is perceived by the male moth with extreme sensitivity and
      specificity. Antennal sensory cells supposedly respond to individual bombykol
      molecules and can efficiently distinguish bombykol from highly related structural
      analogues like bombykal, a second female-released pheromone component. In the
      four decades since the discovery of bombykol, the Bombyx mori system has
      continued to serve as an invaluable model system for unraveling the intricacies
      of chemical communication. The molecular basis for this extraordinary specific
      recognition of an extraneous compound is still elusive but probably based on
      specific receptors of the pheromone-responsive cells. In this study, molecular
      and bioinformatic approaches were employed to search for candidate pheromone
      receptors of Bombyx mori. A few receptor types were identified that are related
      to Heliothis candidate pheromone receptors. They were found to be almost
      exclusively expressed in male antennae, and double in situ hybridization
      experiments disclosed a characteristic topographic expression pattern that was
      reminiscent of pheromone-responsive cells. Furthermore, the receptor-expressing
      cells were closely associated with cells expressing the pheromone-binding
      protein. Together, the data support the view that the identified receptor types
      of Bombyx mori are candidate receptors for pheromone components.

PMID- 15869514
TI  - G-protein coupled activation of potassium channels by endogenous neuropeptides in
      snail neurons.
AB  - Members of the mytilus inhibitory peptide (MIP) family play an important role in
      the modulation of many physiological processes in molluscs. The signal
      transduction pathways affected by the MIP effect have not, however, been
      elucidated. Application of guanosine 5'-[gamma-thio]triphosphate tetralithium
      salt (GTPgammaS), guanosine 5'-[beta-thio]diphosphate trilithium salt (GDPbetaS),
      the G-protein inhibitor suramin and pertussis toxin (PTX) demonstrated the
      involvement of the PTX-insensitive G-protein in the signal transduction pathway
      mediating MIP effects. Both G-protein alpha(i) and betagamma subunits were
      identified in D-neurons of Helix pomatia by immunoblotting. Their role in signal
      transduction was shown in electrophysiological experiments, which supported the
      notion that, in addition to the Galpha subunit, the betagamma dimer also
      participates in the neuropeptide-induced activation of K-channels in snail
      neurons. Finally, neuropeptide-activated responses were inhibited by the
      activation of adenylyl cyclase and by blockers of the phospholipase pathway. We
      suggest that bifurcation of the signal transduction takes place at the level of G
      protein subunits. The alpha subunit may have a direct effect on adenylyl cyclase,
      while the betagamma subunit may have a direct effect on phospholipase enzymes.

PMID- 15869515
TI  - Attraction to sexual pheromones and associated odorants in female mice involves
      activation of the reward system and basolateral amygdala.
AB  - Adult female mice are innately attracted to non-volatile pheromones contained in
      male-soiled bedding. In contrast, male-derived volatiles become attractive if
      associated with non-volatile attractive pheromones, which act as unconditioned
      stimulus in a case of Pavlovian associative learning. In this work, we study the
      chemoinvestigatory behaviour of female mice towards volatile and non-volatile
      chemicals contained in male-soiled bedding, in combination with the analysis of c
      fos expression induced by such a behaviour to clarify: (i) which chemosensory
      systems are involved in the detection of the primary attractive non-volatile
      pheromone and of the secondarily attractive volatiles; (ii) where in the brain
      male-derived non-volatile and volatile stimuli are associated to induce
      conditioned attraction for the latter; and (iii) whether investigation of these
      stimuli activates the cerebral reward system (mesocorticolimbic system including
      the prefrontal cortex and amygdala), which would support the view that sexual
      pheromones are reinforcing. The results indicate that non-volatile pheromones
      stimulate the vomeronasal system, whereas air-borne volatiles activate only the
      olfactory system. Thus, the acquired preference for male-derived volatiles
      reveals an olfactory-vomeronasal associative learning. Moreover, the reward
      system is differentially activated by the primary pheromones and secondarily
      attractive odorants. Exploring the primary attractive pheromone activates the
      basolateral amygdala and the shell of nucleus accumbens but neither the ventral
      tegmental area nor the orbitofrontal cortex. In contrast, exploring the
      secondarily attractive male-derived odorants involves activation of a circuit
      that includes the basolateral amygdala, prefrontal cortex and ventral tegmental
      area. Therefore, the basolateral amygdala stands out as the key centre for
      vomeronasal-olfactory associative learning.

PMID- 15869516
TI  - Nitric oxide release is induced by dopamine during illumination of the carp
      retina: serial neurochemical control of light adaptation.
AB  - Several lines of indirect evidence have suggested that nitric oxide may play an
      important role during light adaptation of the vertebrate retina. We aimed to
      verify directly the effect of light on nitric oxide release in the isolated carp
      retina and to investigate the relationship between nitric oxide and dopamine, an
      established neuromodulator of retinal light adaptation. Using a biochemical
      nitric oxide assay, we found that steady or flicker light stimulation enhanced
      retinal nitric oxide production from a basal level. The metabotropic glutamate
      receptor agonist L-amino-4-phosphonobutyric acid, inhibited the light adaptation
      induced nitric oxide production suggesting that the underlying cellular pathway
      involved centre-depolarizing bipolar cell activity. Application of exogenous
      dopamine to retinas in the dark significantly enhanced the basal production of
      nitric oxide and importantly, inhibition of endogenous dopaminergic activity
      completely suppressed the light-evoked nitric oxide release. The effect of
      dopamine was mediated through the D1 receptor subtype. Imaging of the nitric
      oxide-sensitive fluorescent indicator 4,5-diaminofluorescein di-acetate in
      retinal slices revealed that activation of D1 receptors resulted in nitric oxide
      production from two main spatial sources corresponding to the photoreceptor inner
      segment region and the inner nuclear layer. The results taken together would
      suggest that during the progression of retinal light adaptation there is a switch
      from dopaminergic to nitrergic control, probably to induce further
      neuromodulatory effects at higher levels of illumination and to enable more
      efficient spreading of the light adaptive signal.

PMID- 15869517
TI  - Daily number and lengths of activity bursts in rabbit jaw muscles.
AB  - Muscle activity has predominantly been studied for specific motor tasks not
      necessarily representative of normal daily behaviour. The few studies that have
      examined daily muscle use have quantified this by duty time, merging all levels
      of muscle activity. Muscle activity can also be characterized by the number,
      duration and level of bursts. The purpose of this study was to characterize, for
      various levels of muscle activity, the daily masseter and digastric actions in
      the rabbit. Characterization was realized by quantification of duty time (summed
      length of all bursts as a percentage of total time), number of bursts and
      distribution of burst lengths. A telemetric device was implanted in the two
      muscles of six rabbits, ensuring the recording of their jaw muscle activities
      while they moved freely. The continuously transmitted signals over 1 day were
      analysed. The results showed that (i) more than 100,000 bursts per day exceeded
      the 2% level of the maximum muscle activity in both muscles, whereas fewer than
      100 bursts per day exceeded the 90% level; and (ii) the digastric muscle
      exhibited a significantly higher duty time than the masseter (respectively, 23%
      and 14% for activities exceeding the 2% level), which was mainly caused by the on
      average longer burst lengths at the lowest levels. The characterization of muscle
      activity in daily burst number and distribution of burst lengths exceeding
      various activity levels provides valuable information on motor control and
      enables further investigation of the adaptive capacity of muscles.

PMID- 15869518
TI  - Olfactory learning-induced morphological modifications in single dendritic spines
      of young rats.
AB  - Learning-related morphological modifications in single dendritic spines were
      studied quantitatively in the brains of young Sprague-Dawley rats. We have
      previously shown that olfactory discrimination rule-learning results in transient
      physiological and morphological modifications in piriform cortex pyramidal
      neurons. In particular, spine density along the apical dendrites of neurons from
      trained rats is increased after learning. The aim of the present study was to
      identify and describe olfactory learning-induced modifications in the morphology
      of single spines along apical dendrites of the same type of neurons. By using
      laser-scanning confocal microscopy, we show that 3 days after training completion
      spines on neurons from olfactory discrimination trained rats are shorter as
      compared to spines on neurons from control rats. Further analysis revealed that
      spine shortening attributed to olfactory discrimination learning derives from
      shortening of spine head and not from shortening of spine neck. In addition,
      detailed analysis of spine head volume suggests that spines with large heads are
      absent after learning. As spine head size may be related to the efficacy of the
      synapse it bears, we suggest that modifications in spine head dimensions
      following olfactory rule-learning enhance the cortical network ability to enter
      into a 'learning mode', in which memories of new odours can be acquired rapidly
      and efficiently.

PMID- 15869519
TI  - Reduced basal activity and increased functional homogeneity in sensorimotor and
      striatum of a Parkinson's disease rat model: a functional MRI study.
AB  - Functional neuro-imaging studies of Parkinson's disease (PD) patients and animal
      models show inconsistent cortical responses to sensory stimulation: some present
      increased sensorimotor cortex activation contradicting classical basal ganglia
      cortex circuitry models, whereas others show decreased activation. As functional
      neuro-imaging activation is defined as the signal difference between stimulation
      ON and stimulation OFF, reduced 'activation' can point to either increased
      neuronal activity during stimulation ON or to decreased basal neuronal activity
      during stimulation OFF. A unique non-invasive method that uses the temporal and
      the spatial variances of functional magnetic resonance imaging signal is employed
      here to compare basal neuronal activity levels and 'functional homogeneity'
      between groups. Based on the assumption that the temporal variance reflects
      average neuronal activity, the variance of activity within a predefined region is
      defined as the region's 'functional homogeneity', which is assumed to estimate
      neuronal synchronization. Comparison of temporal and spatial variances of the
      sensorimotor cortex and the striatum in the 6-hydroxydopamine (6-OHDA) PD rat
      model and a control rat group show bilaterally decreased temporal and spatial
      variances in the 6-OHDA rat group, suggesting bilateral reduction of basal
      neuronal activity levels together with an increase in local neuronal
      synchronization in line with classical basal ganglia-cortex circuit models.

PMID- 15869520
TI  - Blockade of melanocortin transmission inhibits cocaine reward.
AB  - Melanocortins and the melanocortin-4 receptor (MC4-R) are enriched in the nucleus
      accumbens, a brain region that has been implicated in the rewarding action of
      cocaine and other drugs of abuse. In the present study we use a number of rat
      behavioral models to show that infusion of a melanocortin peptide antagonist into
      the nucleus accumbens blocks the reinforcing, incentive motivational, and
      locomotor sensitizing effects of cocaine. We also show that locomotor responses
      to repeated cocaine exposure are completely blocked in MC4-R null mutant mice and
      reduced in Agouti mice that overexpress an endogenous inhibitor of melanocortins
      in the brain. The results also demonstrate that cocaine administration increases
      the expression of MC4-R in the nucleus accumbens and striatum, and that MC4-R is
      co-localized with prodynorphin in medium spiny neurons in the nucleus accumbens.
      Together, these findings indicate that the behavioral actions of cocaine are
      dependent on activation of MC4-R, and suggest that upregulation of this receptor
      by drug exposure may contribute to sensitization of these behavioral responses.
      Modulation of cocaine reward is a novel action of the melanocortin-MC4-R system
      and could be targeted for the development of new medications for cocaine
      addiction.

PMID- 15869522
TI  - 'Compulsive' lever pressing in rats is enhanced following lesions to the orbital
      cortex, but not to the basolateral nucleus of the amygdala or to the dorsal
      medial prefrontal cortex.
AB  - In a new rat model of obsessive-compulsive disorder (OCD), 'compulsive' behaviour
      is induced by attenuating a signal indicating that a lever-press response was
      effective in producing food. We have recently found that compulsive lever
      pressing is increased following lesions to the rat orbital cortex, in accordance
      with several lines of evidence implicating the orbitofrontal cortex in the
      pathophysiology of OCD. In view of the functional similarities between the
      orbital cortex, the basolateral nucleus of the amygdala and the medial prefrontal
      cortex, the present study compared the effects of lesions to these three regions.
      The present study replicated the finding that lesions to the rat orbital cortex
      enhance compulsive lever pressing. In contrast, lesions to the dorsal medial
      prefrontal cortex and to the basolateral amygdala did not affect compulsive lever
      pressing. A comparison of these findings to current knowledge regarding
      similarities and differences in the functioning of the three regions sheds light
      on the mechanism by which signal attenuation induces compulsive lever pressing
      and on the role played by the orbital cortex in compulsive behaviour.

PMID- 15869521
TI  - Cannabinoid CB1 receptor antagonism reduces conditioned reinstatement of ethanol
      seeking behavior in rats.
AB  - The endocannabinoid system is involved in a variety of effects of drugs of
      misuse, and blockade of the cannabinoid CB1 receptor by selective antagonists
      elicits marked reductions in opioid and alcohol self-administration. The present
      study was designed to extend our knowledge of the role of the cannabinoid CB1
      receptor in the modulation of alcohol misuse vulnerability in rats. Accordingly,
      using nonselected Wistar rats and genetically selected Marchigian Sardinian
      alcohol-preferring (msP) rats, we investigated the effect of the CB1 antagonist
      SR141716A on operant alcohol self-administration and on reinstatement of alcohol
      seeking behavior by environmental conditioning factors. In addition, in situ
      hybridization studies in both strains were performed to measure cannabinoid CB1
      receptor mRNA in different brain areas of these animals. Results showed that
      intraperitoneal administration of SR141716A (0.03, 1.0 and 3.0 mg/kg) markedly
      inhibits ethanol self-administration and conditioned reinstatement of ethanol
      seeking behavior in both strains of rats. ED50 analysis showed significantly
      higher sensitivity (P < 0.05) to the effect of SR141716A in msP rats than in
      heterogeneous Wistar rats. In situ hybridization studies revealed that, compared
      with Wistar rats, msP animals have consistently greater cannabinoid CB1 receptor
      mRNA expression in a number of brain areas, including the frontoparietal cortex,
      caudate-putamen and hippocampus (CA1 and dentate gyrus areas). In conclusion, we
      provide clear evidence that blockade of CB1 receptors reduces both ethanol self
      administration and conditioned reinstatement of alcohol-seeking behavior in rats.
      In addition, current pharmacological and neuroanatomical data suggest that an
      altered function of the CB1 receptor system exists between genetically selected
      alcohol-preferring msP rats and a heterogeneous animal population.

PMID- 15869523
TI  - Removal of cholinergic input to perirhinal cortex disrupts object recognition but
      not spatial working memory in the rat.
AB  - The perirhinal cortex of the temporal lobe has a crucial role in object
      recognition memory. Cholinergic transmission within perirhinal cortex also seems
      to be important for this function, as the muscarinic receptor antagonist
      scopolamine disrupts object recognition performance when administered
      systemically or directly into perirhinal cortex. In the present study, we
      directly assessed the contribution of cholinergic basal forebrain input to
      perirhinal cortex in object recognition. Selective bilateral removal of the
      cholinergic basal forebrain inputs to perirhinal cortex was accomplished by
      injecting the immunotoxin 192 IgG-saporin directly into perirhinal cortex in
      rats. These animals were significantly impaired relative to vehicle-injected
      controls in a spontaneous object recognition task despite intact spatial
      alternation performance. These results are consistent with recent reports of
      object recognition impairment following acute cholinergic receptor blockade and
      extend these findings by demonstrating that chronic removal of cholinergic basal
      forebrain input to an otherwise intact perirhinal cortex causes a severe object
      recognition deficit similar to that associated with more extensive cell body
      lesions of perirhinal cortex.

PMID- 15869524
TI  - Electrophysiological evidence for cortical plasticity with movement repetition.
AB  - The role of movement repetition and practice has been extensively studied as an
      aspect of motor skill learning but has rarely been investigated in its own right.
      As practice is considered a prerequisite for motor learning we expected that even
      the repetitive execution of a simple movement would rapidly induce changes in
      neural activations without changing performance. We used 64-channel event-related
      potential mapping to investigate these effects of movement repetition on
      corresponding brain activity in humans. Ten healthy right-handed young adults
      performed a power grip task under visual force control to ensure constant
      behaviour during the experimental session. The session consisted of two parts
      intersected by a break. For analysis each part was subdivided into two runs to
      control for potential attention or fatigue effects, which would be expected to
      disappear during the break. Microstate analysis revealed that distinct
      topographies and source configurations during movement preparation, movement
      execution and feedback integration are responsive to repetition. The observed
      patterns of changes differed for the three microstates, suggesting that
      different, repetition-sensitive neural mechanisms are involved. Moreover, this
      study clearly confirms that movement repetition, in the absence of skill
      learning, is capable of inducing changes in neural networks.

PMID- 15869525
TI  - Lasting accelerative effects of 1 Hz and 20 Hz electrical stimulation on cortical
      spreading depression: relevance for clinical applications of brain stimulation.
AB  - Clinical applications of brain stimulation have been increasing during the last
      decade; however, the mechanisms of action remain unknown. One proposed mechanism
      of action is that repetitive stimulation modulates cortical excitability. Herein,
      we explore the question of whether repetitive electric stimulation increases
      cortical excitability as indexed by the cortical spreading depression. Twenty
      four Wistar rats were divided into three groups according to the treatment: sham,
      1-Hz and 20-Hz stimulation. Stimulation was applied to the left frontal cortex
      through a pair of epidurally implanted silver-wire electrodes. The cortical
      spreading depression-features were analysed at three time points (one day before,
      one day after and 2 weeks after treatment) in both the stimulated and
      unstimulated hemisphere. A 3 x 2 x 3 factorial anova with repeated measures
      showed significant differences in the main effect of time (P < 0.0001),
      hemisphere (P = 0.0002) and stimulation group (P = 0.008). The interaction
      between time vs. hemisphere vs. stimulation group was also significant (P <
      0.0001). Posthoc analysis demonstrated that 1-Hz and 20-Hz repetitive electrical
      stimulation significantly increased the velocity of cortical spreading depression
      in the stimulated hemisphere. Furthermore, 20-Hz stimulation showed a greater
      effect on cortical spreading depression compared to 1-Hz stimulation. The results
      show that 1-Hz and 20-Hz repetitive electrical stimulation results in an increase
      in cortical spreading depression velocity that is associated with the frequency
      and the hemisphere of stimulation. Furthermore, the effects are found to be long
      lasting. We believe that these findings have strong relevance to support the
      clinical application of therapies involving electrical stimulation for diseases
      of reduced cortical excitability.

PMID- 15869526
TI  - Speed limits in the cerebellum: constraints from myelinated and unmyelinated
      parallel fibers.
AB  - Cerebellar parallel fibers are among the thinnest known vertebrate axons and
      represent an extreme anatomical adaptation. Until now a systematic examination of
      their properties across species has not been carried out. We used transmission
      electron microscopy and light microscopy to compare parallel fibers in mammals of
      different brain sizes. From mouse to macaque, the average unmyelinated parallel
      fiber diameter was 0.2-0.3 microm, consistent with the idea that they are
      evolutionarily selected for compactness. Average unmyelinated parallel fiber
      diameter scaled up slightly with brain size, and across species the estimated
      total conduction time is 5-10 ms. However, these conduction times can vary by
      milliseconds, and unmyelinated PFs consume large amounts of energy per action
      potential. These functional disadvantages are overcome in myelinated parallel
      fibers, which we found in the deep regions nearest the Purkinje cell layer in
      marmoset, cat and macaque. These axons were 0.4-1.1 microm wide, have expected
      conduction times of 0.5-1.0 ms, and may convey fast feedforward inhibition via
      basket cells to Purkinje cells.

PMID- 15869527
TI  - Over-expression of the human EAAT2 glutamate transporter within neurons of mouse
      organotypic hippocampal slice cultures leads to increased vulnerability of CA1
      pyramidal cells.
AB  - Excitatory amino acid transporters (EAATs) maintain the balance between
      pathological and physiological conditions by limiting the extracellular
      concentration of glutamate within the CNS and thus preventing excitotoxic injury.
      The loss of EAAT2 has been associated with the development of neurological
      diseases such as amyotrophic lateral sclerosis. It has therefore been suggested
      that the over-expression of specific EAATs may provide some degree of
      neuroprotection. However, the inability to isolate and study the function of the
      different EAAT isoforms in a cell type-specific manner has made it difficult to
      determine the exact contribution of individual EAATs toward neuroprotection or
      neurodegeneration in the context of excitotoxic injury. To address this question,
      we transduced hippocampal slice cultures from 1-week-old C57B/6 mice with
      recombinant adeno-associated virus carrying an EAAT2 gene expression cassette.
      EAAT2 gene expression was driven in neurons with the neuron-specific enolase
      promoter. Using this model system, we were able to induce a significant increase
      in the expression of functional EAAT2. Consequently, a significant increase in
      CA1 neuronal damage was observed in slices over-expressing EAAT2 in neurons
      following an acute exposure to exogenous glutamate. These data suggest that the
      increased expression of EAAT2 within neurons may contribute to neurodegeneration.

PMID- 15869528
TI  - The photoperiod entrains the molecular clock of the rat pineal.
AB  - The suprachiasmatic nucleus-pineal system acts as a neuroendocrine transducer of
      seasonal changes in the photoperiod by regulating melatonin formation. In the
      present study, we have investigated the extent to which the photoperiod entrains
      the nonself-cycling oscillator in the Sprague-Dawley rat pineal. For this
      purpose, the 24-h expression of nine clock genes (bmal1, clock, per1, per2, per3,
      cry1, cry2, dec1 and dec2) and the aa-nat gene was monitored under light-dark 8 :
      16 and light-dark 16 : 8 in the rat pineal by using real-time RT-PCR. The 24-h
      pattern of the expression of only per1, dec2 and aa-nat genes was affected by
      photoperiod. In comparison with the short photoperiod, the duration of elevated
      expression under the long photoperiod was elongated for per1 and shortened for
      dec2 and aa-nat. For each of the genes, photoperiod-dependent variations partly
      persisted under constant darkness. Therefore, the pineal clockwork appears to
      memorize the photoperiod of prior entrained cycles. The findings of the present
      study indicate that the nonself-cycling oscillator of the rat pineal is entrained
      by photoperiodic information and therefore that it participates in seasonal
      timekeeping.

PMID- 15869529
TI  - Unilateral optic nerve crush induces bilateral retinal glial cell proliferation.
AB  - The post-injury responses of retinal ganglion cells elicit a number of glial
      reactions which have not been completely understood. The bilateral pattern of non
      neuronal retinal cell proliferation was examined in association with the
      differential fates of unilaterally injured adult retinal ganglion cells by means
      of bromodeoxyuridine (BrdU) immunocytochemistry. Lateralization of the
      glioproliferative events was studied by analysing both the experimental and the
      uninjured contralateral as well as matched retinas of sham-operated animals.
      Control adult rat retina included very few BrdU-positive cells within the nerve
      fibre and ganglion cell layers; however, experimental retinas of degenerating
      groups exhibited statistically significantly higher densities of newborn cells in
      most layers. Clusters of labelled cells were found in the inner plexiform layer
      related to OX-42 staining, indicating their microglial nature. Indeed, double
      labelling experiments, after short-term unilateral optic nerve crushing,
      identified proliferating retinal glial cells in vivo. Both types of glia,
      astroglial and microglial cells, exhibited BrdU-positive labelling in injured as
      well as uninjured experimental rat retinas. Moreover, microglial proliferating
      cells were also identified in explanted retinal pieces after 2 days in culture.
      Affected and contralateral retinas responded similarly to the unilateral
      experimental manipulations applied with respect to BrdU labelling. The acute
      glial responses observed suggest that bilateral glial proliferation might
      represent a common response related to degeneration events in both retinas, i.e.
      ipsi- and contralateral to the experimental injury.

PMID- 15869531
TI  - UVB phototherapy and skin cancer risk: a review of the literature.
AB  - BACKGROUND: UVB phototherapy is a common treatment modality for psoriasis and
      other skin diseases. Although UVB has been in use for many decades, many
      clinicians are hesitant to use this type of phototherapy because of concern over
      increasing the skin cancer risk. Over the past 20 years, numerous studies have
      been published examining this issue, but a consensus or analysis of the skin
      cancer risk is required for the dermatologist to make an educated risk-benefit
      analysis. OBJECTIVE: To assess the risk of skin cancer associated with UVB
      phototherapy. METHODS: All prospective or retrospective studies were identified
      in MEDLINE from 1966 to June 2002. Bibliographies were searched to identify any
      additional studies examining this issue. All studies that attempted to quantify
      or qualify any additional skin cancer risk from UVB phototherapy were included.
      Study selection was performed by two independent reviewers. RESULTS: Eleven
      studies (10 of which concerned psoriasis patients), involving approximately 3400
      participants, were included. Of note, three of the studies involved the same
      cohort: members of the 16-center US Psoralen plus UVA (PUVA) Follow-up Study:
      Other than the most recent Finnish study, all studies eventually showed no
      increased skin cancer risk with UVB phototherapy. One of the PUVA cohort studies
      examined genital skin cancers, and found an increased rate of genital tumors
      associated with UVB phototherapy, although this study has not been duplicated.
      CONCLUSION: The evidence suggests that UVB phototherapy remains a very safe
      treatment modality.

PMID- 15869532
TI  - Basaloid follicular hamartoma.
AB  - Basaloid follicular hamartoma (BFH) is a unique benign follicular hamartoma
      characterized by variable clinical presentations, identical histologic features
      and possible associations with numerous disorders. Basaloid follicular hamartoma
      may be hereditary or acquired. Hereditary cases may be either generalized or
      unilateral nevoid. Although the generalized forms are usually associated with
      systemic manifestations, such as myasthenia gravis,(2) it may occasionally
      present without internal disorders. On the other hand, the acquired forms of BFH
      may present in the form of localized or solitary forms. Herein we present four
      cases of BFH, one of them (first case) represents a unique form of the
      generalized variant of BFH, showing no associated internal disorders.

PMID- 15869533
TI  - Paraneoplastic pemphigus with clinical features of lichen planus associated with
      low-grade B cell lymphoma.
AB  - BACKGROUND: Neoplasia-induced lichen planus is described as a cell-mediated
      reaction to unknown epithelial antigens. Paraneoplastic pemphigus (PNP),
      characterized by the presence of a specific array of autoantibodies, probably
      represents a different form of presentation of the same autoimmune syndrome where
      the mucocutaneous expression depends on the dominant pathologic mechanism.
      METHODS: The authors report a case of PNP with predominant lichen planus-like
      lesions and review the relevant literature. We observed a 74-year-old female with
      vesico-bullous, erosive, target-shaped and flat papular lichenoid lesions on the
      lower legs, palms and soles, evolving for 3 weeks. Histopathology revealed a
      lichenoid dermatitis. Direct immunofluorescence showed C3 deposition around
      keratinocytes and epidermal IgG intranuclear deposition. Indirect
      immunofluorescence revealed circulating IgG with intercellular staining on rat
      bladder substrate. Immunoblotting demonstrated bands of 130, 190, 210 and 250 kDa
      antigens. A pararenal B cell lymphoma was found. RESULTS: Oral corticotherapy
      with 40 mg prednisolone daily was initiated with a good cutaneous response. Four
      months later, cyclophosphamide (50 mg/day) was introduced because of a discrete
      enlargement of the pararenal mass. The patient died on the seventh month of
      follow up as a result of respiratory insufficiency. CONCLUSION: PNP has different
      forms of presentation and the lack of a consensus about diagnostic criteria may
      contribute to underdiagnosed cases. Advances on the knowledge of the sensitivity
      and specificity of diagnostic criteria have allowed a better accuracy of
      diagnosis.

PMID- 15869534
TI  - Effect on quality of life in patients with pityriasis rosea: is it associated
      with rash severity?
AB  - BACKGROUND: It is unknown how the quality of life (QOL) is affected in patients
      with pityriasis rosea (PR), and whether it is related to rash severity. METHODS:
      We constructed a valid and reliable Cantonese version of the Dermatology Life
      Quality Index (DLQI). We recruited patients with PR, with atopic dermatitis and
      with acne vulgaris, and controls of the same sex and comparable age. We applied
      the DLQI and the Pityriasis Rosea Severity Score (PRSS) to the patients with PR,
      the DLQI and the SCORing Atopic Dermatitis Index (SCORAD) to the controls with
      atopic dermatitis, and the DLQI and the Leeds Acne Grading System (LAGS) to the
      controls with acne vulgaris. RESULTS: Total DLQI scores of the 22 patients with
      PR (mean: 6.36, SD: 5.79) were significantly lower than those of the 22 controls
      with atopic dermatitis (mean: 12.00, SD: 5.38) (P = 0.021), but were
      insignificantly different from those of the 22 controls with acne vulgaris (mean:
      6.86, SD: 4.53) (P = 0.57). Correlation between the total DLQI and PRSS scores
      was weak (gamma(s) = +0.19) and insignificant (P = 0.40). All six DLQI parameters
      were insignificantly correlated with the PRSS scores. In contrast, the total DLQI
      scores and most of the DLQI parameters were strongly correlated with the rash
      severity scores for the control subjects. Significantly more patients with PR
      have concerns regarding disease etiology and infectivity. CONCLUSIONS: The QOL of
      the patients with PR was significantly less affected than that for the patients
      with atopic dermatitis, but was insignificantly different from the patients with
      acne vulgaris. Unlike atopic dermatitis and acne vulgaris, the effects on the QOL
      in PR are insignificantly correlated with rash severity. These results bear
      important implications on clinical management.

PMID- 15869535
TI  - Lifestyle of Nordic people with psoriasis.
AB  - AIM: The Nordic Quality of Life Study was undertaken to assess the relationship
      between psoriasis and the quality of life in Nordic countries. The intention was
      also to determine whether there was a relationship between drinking, smoking, and
      the use of psychotherapeutic agents on the one hand, and psoriasis severity and
      quality of life on the other. MATERIALS AND METHODS: A questionnaire was mailed
      to 11,300 members of the Nordic Psoriasis Associations. Additional psoriasis
      patients were recruited by dermatologists (387) or admitted to dermatologic wards
      (385). These patients also underwent a physical examination, and their Psoriasis
      Area and Severity Index (PASI) was determined. The questionnaire included the
      Psoriasis Disability Index (PDI), Psoriasis Life Stress Inventory (PLSI), and
      additional questions on disease severity, treatment, and psoriasis arthritis. It
      also included questions regarding lifestyle issues, such as smoking, alcohol use,
      and the use of tranquilizers, antidepressants, and sleeping medications. RESULTS:
      The response rate for members was 50.2%. Included in the evaluation were 6497
      patients. Men drank significantly more beer and liquor than women. The number of
      beers per day had a weak correlation with the PDI. Wine consumption, however,
      showed a weak, but significant, negative correlation with both PDI and PLSI.
      Patients admitted to dermatologic wards smoked more cigarettes and drank less
      wine than the other two groups. Significant differences were found between
      countries with regard to total alcohol consumption and cigarette smoking. The
      number of cigarettes and the use of tranquilizers, sleeping medications, and
      antidepressants showed small, but significant, positive correlations with
      psoriasis quality of life measures. CONCLUSIONS: Cigarette smoking and the use of
      tranquilizers, sleeping medications, and antidepressants are statistically
      correlated with impaired psoriasis-related quality of life.

PMID- 15869536
TI  - Skin diseases highlighting essential global public health priorities.
AB  - Which are the essential global public health activities that should be carried
      out in order to attain the largest impact on poverty reduction and health
      improvement in the world? Since its foundation in 2001 the Human Mobile
      Population Committee (HMPC) has continued to devote its efforts to finding
      answers to this question, with a particular focus on the skin diseases of the
      Human Mobile Population (HMP) and other groups of disadvantaged people. In this
      article we present the model of socio-sanitary activity in the field of
      Migration, Poverty and Health of the Department of Preventive Medicine of
      Migration, Tourism and Tropical Dermatology (Dept.) at San Gallicano Institute-
      Research Institute for Hospitalization and Treatment (IRCCS)--in Rome (Italy).
      The activities of this dermatological centre are in the spirit of the HMPC's aims
      and we are of the opinion that this model is not only ethically valid, but also
      practically and economically convenient, and that there is evidence that our
      experience is worth repeating, in as many situations as possible, in the interest
      of public health.

PMID- 15869537
TI  - Genital ulcer disease and human immunodeficiency virus: a focus.

PMID- 15869538
TI  - Acrokeratoelastoidosis.
AB  - A 45-year-old white woman presented with several years' history of firm, shiny
      papules on the lateral hands with slight extension to the dorsal fingers. The
      lesions first appeared between the index fingers and thumbs on both hands. They
      gradually increased in number, coalescing into plaques and affecting the junction
      between the palmar and dorsal skin. The patient did not have involvement of her
      feet. She had been diagnosed previously with chronic eczema that had failed to
      respond to multiple topical medications. In addition, the patient's sister had
      similar lesions on both hands. The patient denied any symptoms of hyperhidrosis,
      excessive sun exposure, or trauma. The plaques were asymptomatic, but were
      cosmetically unappealing to the patient. On physical examination, small, firm,
      skin-colored, hyperkeratotic papules, coalescing into plaques, were located on
      the junction between the palmar and dorsal skin on both lateral margins of the
      thumb and on the radial side of the index finger (Fig. 1). There were no lesions
      on the feet. A biopsy taken from a papule on the patient's left hand was
      consistent histologically with acrokeratoelastoidosis. The biopsy showed marked
      degeneration of collagen in the dermis with solar elastosis and some smudging of
      the papillary dermal collagen (Fig. 2). She was treated with clobetasone cream to
      the affected areas on the hands. After 6 weeks of treatment, she reported no
      significant improvement.

PMID- 15869539
TI  - Lipoid proteinosis: report of a possible localized form on both hands and wrists.
AB  - A 28-year-old woman was seen for pruritic lesions on both hands and wrists which
      had been present since the age of 10 years. Both palms showed symmetric, diffuse
      hyperkeratosis extending over both wrists and the dorsal aspects of both hands
      with well-demarcated, erythematous, lichenified plaques (Figs 1 and 2). The
      borders of the plaques were pigmented and studded with papules (Fig. 2). The skin
      lesions were not related to sun exposure. No similar lesions were found elsewhere
      on the body. The hair, nails, and dental development were normal. A skin biopsy
      was taken for histopathologic and ultrastructural studies under the clinical
      impression of pityriasis rubra pilaris. Microscopically, homogeneous perivascular
      deposits of hyaline-like material were seen in the papillary and reticular
      dermis, accompanied by mononuclear cells (Figs 3 and 4). The overlying epidermis
      was acanthotic with hyperkeratosis (Fig. 3). The hyaline deposits were positive
      for periodic acid-Schiff (PAS) and oil-red O stains (Figs 5 and 6). Congo red
      stain was negative. Electron microscopic examination showed abundant amorphous
      material intermingled with short collagen fibrils in the dermis and around the
      blood vessels (Figs 7 and 8). Further examination revealed that the patient could
      protrude her tongue freely. The oral mucosa and vocal cords were smooth. There
      was no sign of systemic amyloidosis. The patient's complete blood cell count,
      biochemical tests, and protein electrophoresis were all within normal limits.
      Antinuclear antibody was negative. Results of porphyrin screening tests were
      negative for uroporphyrins and coproporphyrins in the urine and feces. The
      possibility of porphyria was therefore excluded. Both neurologic and ophthalmic
      examinations were negative. No intracranial calcification was found on a skull X
      ray examination. The patient was treated with topical steroid and urea. She was
      lost to follow-up.

PMID- 15869540
TI  - Scar sarcoidosis after hyaluronic acid injection.
AB  - A 54-year-old woman presented with a 5-month history of tender nodules in both
      nasolabial folds that had developed 4 months after the injection of hyaluronic
      acid (HA) (Restylane) for wrinkles. The patient was treated with 1.5 mg/day
      betamethasone for 6 days and her lesions disappeared within 1 week. About 8 days
      after stopping therapy, however, new nodules developed at the same site, on
      previously healthy buttocks, and on old scars. On examination, nodules of about
      0.5-1 cm in size were palpable at the nasolabial folds, and red nodules were
      present on the buttocks (Fig. 1) and on two old scars. Laboratory tests disclosed
      an increased protein C reaction (7.9 mg/L; normal value, < 5 mg/L) and acetyl
      converting enzyme test (14.5 U/L; normal value, < 9 U/L). A chest X-ray was
      normal. Lung function tests showed a decreased lung CO diffusion, and chest axial
      tomography disclosed fibrosis, increased parenchyma density, and calcifications,
      findings suggestive of a diagnosis of lung sarcoidosis. An X-ray of the hands
      showed some bone cysts. Interestingly, two granulomatous lesions were observed at
      the sites of venipuncture. Histology of a gluteal lesion biopsy showed a deep
      granuloma with epithelioid and Langhans cells in the absence of necrobiosis.
      Sarcoidosis was diagnosed and the patient was given 50 mg/day prednisone with
      clear clinical improvement of cutaneous lesions in about 6 months. Decreased
      parenchyma density was also observed by chest axial tomography.

PMID- 15869541
TI  - Tinea capitis mimicking dissecting cellulitis: a distinct variant.
AB  - BACKGROUND: Tinea capitis is a common scalp dermatosis with several clinical
      patterns. Only two patients with a presentation of tinea capitis mimicking
      dissecting cellulitis have been described in the English literature. OBSERVATION:
      We report a patient with tinea capitis mimicking dissecting cellulitis who did
      not respond to griseofulvin therapy at 16 mg/kg/day but eventually cleared after
      a protracted course of higher dose griseofulvin. CONCLUSION: recognition of a
      dissecting cellulitis-like pattern of tinea capitis will increase clinical
      suspicion and avoid inappropriate management of a recalcitrant "dissecting
      cellulitis" in favor of prompt antifungal therapy of appropriate dosage and
      duration for patients with this unusual variant of tinea capitis.

PMID- 15869542
TI  - Trichoepitheliomas and eccrine spiradenomas with spiradenoma/cylindroma overlap.

PMID- 15869543
TI  - Pilot study of the safety and efficacy of Myobloc (botulinum toxin type B) for
      treatment of axillary hyperhidrosis.
AB  - BACKGROUND: Botulinum toxin type B (BTX-B, Myobloc, San Francisco, CA, USA) was
      FDA-approved for the treatment of cervical dystonia in December 2000. It has
      since been used off-label for the treatment of axillary hyperhidrosis. However,
      there are sparse data in the medical literature evaluating the safety and
      efficacy of Myobloc (botulinum toxin type B) for this indication. OBJECTIVE: To
      assess the safety, efficacy and duration of action of Myobloc (botulinum toxin
      type B) in the treatment of bilateral axillary hyperhidrosis. METHODS: This study
      was a double-blinded, randomized, pilot study conducted in an outpatient office
      setting at a private academic medical center beginning in November 2001. Twenty
      three male and female volunteers between the ages of 18 and 80 were screened for
      participation; 20 participants with primary axillary hyperhidrosis were enrolled.
      Participants were injected subcutaneously with either Myobloc (botulinum toxin
      type B) (2500 U, or 0.5 ml, per axilla) or 0.5 ml vehicle (100 mM NaCl, 10 mM
      succinate, and 0.5 mg/ml human albumin) into bilateral axillae. Participants who
      received placebo were rolled over and received Myobloc (botulinum toxin type B)
      at subsequent visits. All participants were followed until sweating returned to
      baseline levels. This trial was initially conceived as a placebo-controlled
      study; however, owing to the insufficient size of the placebo group, the placebo
      arm of this trial was dropped during data analysis. The main outcome measures
      were safety, efficacy, and duration of effect. RESULTS: According to participant
      assessment of axillary hyperhidrosis improvement (A-HI) and quality of life (A
      HQOL) scores and the physician assessment scores, a significant difference was
      observed in treatment response at Day 30 in the participants receiving Myobloc
      (botulinum toxin type B) injections. Duration of action ranged from 2.2 to 8.1
      months (mean 5.0 months). The adverse event profile included bruising, flu-like
      symptoms, and dry eyes. CONCLUSION: Myobloc (botulinum toxin type B) proved to be
      safe and efficacious for the treatment of bilateral axillary hyperhidrosis. More
      studies are needed to assess the duration of response using different doses of
      Myobloc (botulinum toxin type B).

PMID- 15869544
TI  - Effect of topical corticosteroid application frequency on histamine-induced
      wheals.
AB  - BACKGROUND: Very few studies have been conducted to assess the effect of
      corticosteroid application frequency to attain maximum benefit with minimum side
      effects. OBJECTIVES: Compare the efficacy of twice-daily, once-daily and
      alternate-day applications of clobetasol propionate (0.05%) and compare whether
      an initial once-daily application followed by a subsequent alternate-day
      application is as effective as a once-daily application. METHODS: The ability of
      corticosteroids to suppress histamine-induced wheals on human skin was used as a
      human bioassay model. Of the 26 subjects included, 21 completed the 1st phase. In
      the 2nd phase, 11 subjects were included and all completed the study. Four sites
      were chosen on the left forearm. Clobetasol propionate (0.05%) was applied twice
      daily, once daily, and on alternate days, and on the control site a color,
      texture and odour-matched vehicle was applied. Prick test with histamine was
      carried out after 10 days. In the 2nd phase, clobetasol propionate (0.05%) was
      applied once daily for 14 days and compared with the initial once daily for 7
      days and the subsequent alternate-day application for 7 days. Prick test was
      carried out after 14 days. RESULTS: The once-daily application of clobetasol
      propionate (0.05%) was as effective as the twice-daily application, but the
      alternate-day application was less effective than the once-daily application (P <
      0.01). Also, the initial-daily and subsequent alternate-day applications were not
      as effective as the continuous once-daily application (P < 0.05). CONCLUSION: A
      once-daily application of clobetasol propionate (0.05%) is likely to provide the
      required therapeutic effect.

PMID- 15869545
TI  - Successful treatment of malignant melanoma in situ with topical 5% imiquimod
      cream.
AB  - BACKGROUND: Current treatment recommendations for malignant melanoma in situ
      include surgical excision with at least 0.5 cm margins. On the head or neck,
      obtaining adequate surgical margins for melanoma can be challenging and often
      disfiguring. In addition, some elderly patients may not be good surgical
      candidates and may request less aggressive interventions. METHODS: We report
      herein three cases of malignant melanoma in situ on the face treated with topical
      imiquimod cream. RESULTS: Complete regression of malignant melanoma in situ was
      observed on treatment with 5% topical imiquimod cream. The varied treatment
      regimens, rationale for using imiquimod rather than performing surgery, and the
      possible mechanisms of action are discussed. CONCLUSIONS: Topical imiquimod can
      be used successfully for the treatment of malignant melanoma in situ on the face.

PMID- 15869547
TI  - Lichen planus-type drug eruption resulting from ticlopidine.

PMID- 15869549
TI  - Alopecia areata: a specific personality?

PMID- 15869551
TI  - Measures of surgical quality: what will patients know by 2005?
AB  - RATIONALE, AIMS AND OBJECTIVES: Many objective measures rating quality of
      doctors, hospitals, and medical groups are publicly reported. Surgical patients
      may have more opportunity to use quality measures than other types of patients to
      guide their choice of provider. If surgical patients are able to choose higher
      quality providers, overall surgical quality might increase. OBJECTIVE: To
      determine what procedure-specific measures of surgical quality are available to
      consumers facing surgery in California and what new measures will be available by
      2005. METHODS: We searched for and surveyed organizations publicly reporting data
      on health care quality in California. We asked about current quality measures and
      new measures set for public release by 2005. Included measures had to be
      procedure-specific and results separated by hospital. The main outcome measures
      were the number of quality measures; conceptual aspect of quality measured; and
      type of risk-adjustment used. RESULTS: Eighteen organizations publicly report any
      health care quality measures in California. These organizations report 333
      measures, of which 32 (10%) are procedure-specific measures of surgical quality.
      There is at least one quality measure for 21 different procedures; these
      procedures account for 14% of all major operations. Three new measures will be
      released by 2005. CONCLUSIONS: Californians facing surgery have limited
      information regarding quality of their care; few new measures are planned. Eighty
      six per cent of patients would find no quality measures related to planned
      procedures. Public release of performance data is unlikely to improve the quality
      of health care unless the number and comprehensiveness of measures increase
      dramatically.

PMID- 15869552
TI  - Evaluation of the personal dental services (wave 1) for Lambeth, Southwark and
      Lewisham primary care trusts--Part 1: Retrospective analyses of registration data
      and access issues.
AB  - AIM/OBJECTIVE: The purpose of the study was to undertake analyses of registration
      data for the personal dental services (PDS) of Lambeth, Southwark and Lewisham
      primary care trusts and relate the analyses to the PDS goal of increasing uptake
      of dental services. METHOD: Secondary analyses of registration statistics
      provided by the Dental Practice Board were undertaken for both 1 years pre-PDS
      (October 1997 to September 1998) and post-PDS (October 1998 to March 2003)
      periods. Three sets of analyses were undertaken to consider different aspects of
      changing registrations: (1) Absolute numbers of patients registered at each time
      interval; (2) Rates of change in numbers of patients registered for the entire
      period after the introduction of PDS; and (3) Rates of change in numbers of
      patients registered for the most recent 3 years of available data. RESULTS: There
      was a significant increase in the numbers of children registered under
      capitation, post-PDS as compared to the pre-PDS level (all ages and both genders
      combined). Post-PDS, the rate of increase for the children was approximately one
      additional child per practice per month (0.96, 95% CI 0.41-1.52). Similarly there
      was a significant trend for increasing adults registrations over time of about
      two and a half adults per practice per month (2.42, 95% CI 0.90-3.95). There was
      no evidence of a change in registrations for children or adults in total over the
      most recent period of 3 years. CONCLUSIONS: The analysis of the absolute numbers
      of registered patients each month indicated that the PDS practices had more
      children registered than before the implementation of the PDS scheme, but not
      adults. Overall post-implementation there was a trend for increasing
      registrations in both children and adults, but the most recent data indicated a
      plateau effect. Further consideration of facilitators to achieve PDS goals of
      improved uptake of services is required, particularly as they relate to local
      contexts.

PMID- 15869553
TI  - Evaluation of the personal dental services (wave 1) for Lambeth, Southwark and
      Lewisham primary care trusts--Part 2: Retrospective analyses of treatment and
      other dental record data.
AB  - AIM/OBJECTIVE: The purpose of the study was to undertake analyses of treatment
      data for the Personal Dental Services (PDS) of Lambeth, Southwark and Lewisham
      Primary Care Trusts and relate the analyses to the PDS goals of supporting
      practitioners deliver appropriate quality dental care and ensuring that
      appropriate quality safety net services are available for all residents. METHOD:
      Analyses of treatment data provided by the Dental Practice Board were undertaken
      for the post-PDS period (February 1999-March 2003, based on data availability).
      Analyses of the clinic notes for 1500 patients were also undertaken for the 1
      year pre-PDS period (October 1997-September 1998) and post-introduction of the
      PDS (October 1998-June 2003). Two sets of analyses were undertaken to evaluate
      trends in treatment claims for the Dental Practice Board data, absolute numbers
      of each type of treatment claimed each month and change in numbers of types of
      treatments claimed over time. The clinic notes were used to undertake post-PDS,
      pre-PDS comparisons of the number of treatment items and grouped treatment item
      categories undertaken and the number of courses and percentages of private
      treatment items provided. The following sociodemographic characteristics of the
      patients were also analysed, age, gender, exemption status and attendance status.
      RESULTS: Overall it was identified that the percentage reduction in the number of
      treatment items undertaken was 13% (95% CI -19%, -7%), post- as compared to the
      pre-PDS introduction period. On an annual basis it was identified that the
      percentage reduction in the number of treatment items undertaken per year per
      patient post-PDS was 4% (95% CI -6%, -2%). There were significant variations in
      the impact of the PDS on the number of treatment items undertaken for different
      types of patients. A limited number of treatment types changed significantly post
      as compared to pre-PDS. The proportion of exempt patients treated did not
      increase post-PDS. CONCLUSIONS: It is possible that a less invasive style of
      dental treatment was provided during the course of the PDS, however, there was
      only limited evidence to indicate that dentists practice style changed based on
      types of treatment categories provided. The PDS provided a limited safety net
      service for local residents. In setting program goals the nature of quality
      dental practice requires definition and evaluation should be undertaken on a
      prospective basis.

PMID- 15869554
TI  - Measuring men's preferences for involvement in medical care: getting the question
      right.
AB  - RATIONALE, AIMS AND OBJECTIVES: Now that active involvement by patients in their
      health care is widely endorsed, valid and reliable methods for determining
      preferences for involvement in treatment decision making are essential.
      Relatively little methodological work has been conducted to compare and contrast
      their reliability and validity. Available single-item measures exist to determine
      preferences, ranging from 'menu-based' questions to simpler Likert-type scales.
      METHODS: Within a larger community survey of 514 men aged 50-70 years in Sydney,
      Australia, we compared two measures to assess their preferences for involvement
      in medical decision making. Using the 'menu-based' Control Preference Scale
      (CPS), men were classified as preferring to be either 'passive' or 'active'
      during decision making or to share ('shared') with their doctors on an equal
      basis. Men also were classified as preferring to be either 'passive' or 'active'
      according to a Likert-scale measure. RESULTS: Agreement between the two measures
      was 'poor' (kappa=0.19). While 24.9% of participants were classified as
      preferring a 'passive' role in treatment decision making according to the CPS,
      almost half (47.9%) were so classified according to Arora and McHorney's measure.
      In the absence of a 'shared' response option on the Arora and McHorney measure,
      45.3% of men classified as preferring a 'shared role' on the CPS were instead
      categorized as 'passive' using Arora and McHorney's measure. Predictors of
      preferring a 'passive' role also differed, depending on the measure employed.
      Only occupational skill level predicted men's preferences for a 'passive' role
      when measured by the CPS [odds ratio (OR)=1.67; 95% CI 1.09-2.55] (P=0.02). For
      the Arora and McHorney's measure of preferences for involvement, men were
      significantly more likely to prefer a 'passive' role if they were older [adjusted
      odds ratio (AOR)=1.06, 95% CI 1.02-1.09] (P=0.001), currently smoking (AOR=1.86,
      95% CI 1.09-3.17) (P=0.02) and had higher chance health locus of control scores
      (AOR=1.26; 95% CI 1.01-1.56) (P=0.04). Having been employed or previously
      employed in an occupation of a lower skill level was also significantly and
      independently predictive of a passive role (AOR=2.35, 95% CI 1.57-3.50)
      (P<0.001). CONCLUSIONS: Single-item measures of decisional preferences have poor
      convergent validity. Characteristics associated with preference classifications
      also differ, depending upon the measures used. These results suggest that
      research efforts should be directed towards developing psychometrically robust
      measures to determine decisional preferences.

PMID- 15869555
TI  - Impact of a community pharmacist-directed clinic in improving screening and
      awareness of osteoporosis.
AB  - RATIONALE, AIMS AND OBJECTIVES: There is a need to increase screening and
      awareness of osteoporosis risk in order to prevent fractures and related
      morbidity. Although one in two women are at risk of developing the condition,
      only one in five receives bone mineral density screening. The purpose of the
      current study was to investigate the effectiveness of an osteoporosis screening
      and awareness programme directed by a pharmacist in the community setting.
      METHODS: The study design to test for improved awareness was a prospective, pre
      post trial with no control group. The level of awareness of risk was assessed
      both before the screening and following an educational intervention on
      osteoporosis provided in the pharmacy. Based on assessed risk level, a
      recommendation was made for follow-up with a doctor for a dual-energy X-ray
      absorptiometry (DEXA) scan and/or pharmacotherapy. Patients at medium or high
      risk were also surveyed as to their intention to follow-up with lifestyle
      modification recommendations. RESULTS: There was a significant improvement in
      tested awareness from pre- to post-intervention at 26%; as well in self-rated
      awareness. There was also a significant correlation between self-rated and tested
      awareness. Participants indicated satisfaction with the pharmacist interaction
      and with their role in improving awareness. A large percentage of participants
      indicated that they intended to follow-up with the pharmacist's recommendation
      for calcium intake, exercise and/or consulting with their doctor. CONCLUSION: The
      results indicate that the community pharmacist can successfully screen
      individuals for risk of osteoporosis and improve their awareness about steps to
      prevent or delay fractures.

PMID- 15869556
TI  - Strengthening the HIV/AIDS service delivery system in Liberia: an international
      research capacity-building strategy.
AB  - Liberia's prolonged post-conflict transition has negatively impacted its health
      infrastructure, including the functioning of its health care delivery system.
      Considering the current national health crises, a study was conducted to identify
      research gaps and the need to propose changes for improving the health care
      delivery system in the country. The study results clearly demonstrated a lack of
      HIV/AIDS research infrastructure including organizational structure, linkages,
      leadership, champions, expertise, resources, and policies and procedures.
      Alignment of research needs and practice, and research use to support HIV/AIDS
      service delivery programmes in the country was also limited. An international
      research capacity-building partnership is proposed as an effective planned change
      strategy to strengthen HIV/AIDS-related research infrastructure and to inform
      management and practice within the Liberian HIV/AIDS service delivery system. A
      proposed capacity-building planning model can also strengthen research
      infrastructure and the production and use of research to positively impact the
      HIV/AIDS epidemic in Liberia and other developing countries.

PMID- 15869557
TI  - Changes in mortalities and hospital admissions associated with holidays and
      respiratory illness: implications for medical services.
AB  - RATIONALE AND OBJECTIVES: To see whether net mortalities increase during and
      after reductions in medical services, either at average weekends, or at Christmas
      when pressure from illness is unusually high. METHODS: (1) Paired t-tests to
      compare mean daily deaths and hospital admissions during and after weekends
      (Saturday-Tuesday) with means for the week, in south-east England; (2) Linear
      regressions to see whether trends of daily deaths change when admissions are
      reduced at Christmas. RESULTS: Neither mean daily all-cause, respiratory or
      ischaemic heart deaths exceeded weekly averages during weekends, or during
      Saturday-Monday or Saturday-Tuesday, despite falls in daily elective and daily
      emergency hospital admissions at weekends that averaged 61-72% and 14-22%,
      respectively. During 19-24 December, daily deaths were above annual means,
      respiratory deaths by 49% (29, 1-58), but elective admissions fell and although
      emergency admissions tended to rise, total admissions rose only for respiratory
      disease, and only by 33% (376, -47 to 799). On Christmas Day (25 December), even
      emergency admissions fell sharply below previous trends, respiratory emergency
      admissions by 18% (P<0.01). Respiratory deaths alone then immediately increased
      (P<0.01) above trend, by 5.9% (5.8 deaths/day) on 26 December and by 12.9% (12.9)
      on 27 December. CONCLUSIONS: No adverse effect on mortality was apparent within 2
      days from reduction in medical services at weekends. However, respiratory deaths
      accelerated sharply after reduction in elective and emergency admissions at
      Christmas, when rates of infection and mortality from respiratory disease were
      high. Implications for medical services during respiratory epidemics are
      discussed.

PMID- 15869558
TI  - Costs and effectiveness of pre- and post-operative home physiotherapy for total
      knee replacement: randomized controlled trial.
AB  - AIMS AND OBJECTIVES: To assess the effectiveness of pre- and post-operative
      physiotherapy at home for unilateral total knee replacement (TKR). METHODS: In
      this pragmatic randomized controlled trial set in participants' homes (four
      primary care trust areas) and physiotherapy outpatients in a South Yorkshire
      teaching hospital trust, 160 osteoarthritis patients waiting for unilateral TKR
      were randomly allocated to intervention (home) group (n=80) or control (hospital
      outpatient) group (n=80). The intervention group had pre- and post-operative home
      visits for assessment and treatment by a community physiotherapist. Outcome
      measures were health-related quality of life (HRQoL), measured by the Western
      Ontario McMaster Osteoarthritis index (WOMAC) and the Short Form 36 health survey
      (SF-36) pre-operatively and at 12 weeks post-TKR operation; patient satisfaction;
      and NHS resource use. RESULTS: No significant differences were observed between
      the two treatment groups in the primary outcome measure, the WOMAC pain score, or
      any other HRQoL score. The home group had a significantly greater mean number of
      physiotherapy sessions than the hospital group [mean difference 5.2 sessions, 95%
      confidence interval (CI)=-6.3 to -4.1; P=0.001]. There was no significant
      difference in the total NHS costs per patient between groups. However, home
      physiotherapy for TKR was significantly more expensive (mean difference
      pound136.5, 95% CI=- pound160 to-pound113; P=0.001). Patients were equally
      satisfied with physiotherapy at home or in hospital; however, more of the home
      group would choose their location for physiotherapy again. CONCLUSIONS: Although
      home physiotherapy was as effective and as acceptable to patients as hospital
      outpatient physiotherapy for unilateral TKR, it was more expensive. Additional
      pre-operative home physiotherapy did not improve patient-perceived health
      outcomes.

PMID- 15869559
TI  - Cost and benefits of a multidisciplinary intensive diabetes education programme.
AB  - OBJECTIVES: To determine the cost and benefits of an intensive diabetes education
      programme for patients with prolonged self-management problems and to determine
      the inclusion criteria for optimal outcomes. METHODS: Sixty-one participants of a
      multidisciplinary intensive diabetes education programme (MIDEP) were measured
      before they started the intervention (T0), and at 1-year follow-up (T1). Data on
      glycaemic control (HbA1c), diabetes-related distress (PAID) and costs were
      obtained. Changes over time were analysed and means at T0 and T1 were compared to
      a reference group of 230 non-referred consecutive outpatients. The number needed
      to treat (NNT), that is, the number of patients to be treated to achieve one
      successful case, was calculated for different baseline values of HbA1c and PAID
      to determine optimal inclusion criteria. RESULTS: Diabetes-related costs
      decreased significantly and participants improved significantly in HbA1c and
      diabetes-related distress following MIDEP. HbA1c and distress reached the levels
      of the reference group. The T1 costs remained higher than in the reference group,
      but the reduction in costs outweighed the intervention costs. Including patients
      with baseline HbA1c>or=8.0% and/or PAID scores>or=40 would improve the NNT to
      achieve clinically relevant outcomes, while 76% of the patients matched these
      inclusion criteria. CONCLUSIONS: MIDEP is effective in improving glycaemic
      control and diabetes-related distress for patients with prolonged self-management
      difficulties. Besides the immediate reduction in costs found in the present
      study, improved glycaemic control may reduce future costs of diabetic
      complications. Stricter inclusion criteria with respect to HbA1c and PAID scores
      may further improve the programme's efficiency.

PMID- 15869560
TI  - Characterization of gonadotrophin-releasing hormone precursor cDNA in the Old
      World mole-rat Cryptomys hottentotus pretoriae: high degree of identity with the
      New World guinea pig sequence.
AB  - Regulation of pituitary gonadotrophins by the decapeptide gonadotrophin-releasing
      hormone 1 (GnRH1) is crucial for the development and maintenance of reproductive
      functions. A common amino acid sequence for this decapeptide, designated as
      'mammalian' GnRH, has been identified in all mammals thus far investigated with
      the exception of the guinea pig, in which there are two amino acid substitutions.
      Among hystricognath rodents, the members of the family Bathyergidae regulate
      reproduction in response to diverse cues. Thus, highveld mole-rats (Cryptomys
      hottentotus pretoriae) are social bathyergids in which breeding is restricted to
      a particular season in the dominant female, but continuously suppressed in
      subordinate colony members. Elucidation of reproductive control in these animals
      will be facilitated by characterization of their GnRH1 gene. A partial sequence
      of GnRH1 precursor cDNA was isolated and characterized. Comparative analysis
      revealed the highest degree of identity (86%) to guinea pig GnRH1 precursor mRNA.
      Nevertheless, the deduced amino acid sequence of the mole-rat decapeptide is
      identical to the 'mammalian' sequence rather than that of guinea pigs. Successful
      detection of GnRH1-synthesizing neurones using either a guinea pig GnRH1
      riboprobe or an antibody against the 'mammalian' decapeptide is consistent with
      the guinea pig-like sequence for the precursor and the classic 'mammalian' form
      for the decapeptide. The high degree of identity in the GnRH1 precursor sequence
      between this Old World mole-rat and the New World guinea pig is consistent with
      the theory that caviomorphs and phiomorphs originated from a common ancestral
      line in the Palaeocene to mid Eocene, some 63-45 million years ago.

PMID- 15869561
TI  - GABAergic modulation of the expression of genes involved in GABA synaptic
      transmission and stress in the hypothalamus and telencephalon of the female
      goldfish (Carassius auratus).
AB  - GABA is one of the most abundant neurotransmitters in the vertebrate central
      nervous system and is involved in neuroendocrine processes such as development,
      reproduction, feeding and stress. To examine the effect of GABA on gene
      expression in the brain, we used a cDNA macroarray containing 26 genes involved
      in GABA synaptic transmission (GABA receptor subunits, GABA transporters),
      reproduction (gonadotrophin-releasing hormone isoforms and oestrogen receptor
      alpha), feeding (neuropeptide Y and cholecystokinin), and stress [corticotrophin
      releasing factor (CRF)]. To elevate GABA levels in the brain, we injected female
      goldfish with gamma-vinyl GABA (300 microg/g of body weight) (24 h), an
      irreversible inhibitor of the enzyme GABA transaminase (GABA-T). We found that
      increased levels of GABA in the hypothalamus resulted in a 2.2-fold down
      regulation of GABA(A) receptor beta4 subunit mRNA. In the telencephalon, we found
      that increased GABA levels resulted in a 1.5-fold increase of CRF mRNA and a 1.8
      fold decrease of GABA(A) receptor beta2 subunit mRNA. Increasing GABA in the
      hypothalamus and telencephalon of the goldfish did not significantly affect the
      mRNA abundance of genes involved in GABA synthesis (glutamic acid decarboxylase
      isoforms) and degradation (GABA-T), feeding, or reproduction. Our preliminary
      study suggests that the regulation of GABA receptor subunit mRNA expression by
      GABA may be a conserved evolutionary mechanism in vertebrates to modulate
      GABAergic synaptic transmission.

PMID- 15869562
TI  - Involvement of 5-HT receptors in the regulation of food intake in Siberian
      hamsters.
AB  - The Siberian hamster provides a physiological model for understanding the
      hypothalamic control of energy metabolism as it undergoes annual photoperiod
      regulated cycles of body weight (i.e. fattening in summer, and catabolism of fat
      stores in winter). As a first step to investigate whether enhanced serotonergic
      (5-HT) tone might underlie the catabolic processes in short days, we investigated
      whether serotonergic stimulation can produce catabolic actions in fat hamsters
      housed in long days. Acute treatment with the serotonin reuptake inhibitor (+/-)
      fenfluramine (8 mg/kg, i.p.) produced a prolonged, dose-dependent reduction in
      food intake in both photoperiods. Behavioural observations and radiotelemetry
      analyses revealed that this anorectic effect of fenfluramine was associated with
      short-term increases in locomotor activity and in core body temperature. In a
      subsequent series of studies, hamsters were pretreated with the 5-HT2C receptor
      antagonist SB242084 (4 mg/kg, i.p.). This 5-HT2C receptor antagonist completely
      blocked the anorectic actions of fenfluramine, but did not decrease the
      hyperthermia or hyperlocomotion induced by fenfluramine; thus, the anorectic
      actions of fenfluramine probably reflect actions via the 5-HT2C receptor.
      Consistent with these observations, treatment of hamsters with the 5-HT2C
      receptor agonist VER 3323 (10 mg/kg, i.p.) or the 5-HT1B/2C receptor agonist mCPP
      (3 mg/kg, i.p.) reduced food intake. The response to manipulation of serotonergic
      pathways was not affected by the ambient photoperiod in any of these studies. We
      conclude that the anorectic actions of fenfluramine are not an indirect
      consequence of serotonergic actions on arousal pathways, and that its actions on
      feeding in the Siberian hamster are most likely to be mediated by the 5-HT2C
      receptor.

PMID- 15869563
TI  - Expression of functional ciliary neurotrophic factor receptors in immortalized
      gonadotrophin-releasing hormone-secreting neurones.
AB  - Ciliary neurotrophic factor (CNTF), a cytokine of the interleukin-6 superfamily,
      is known to exert pleiotropic actions, including regulation of food intake and
      permissive effects on reproduction, by facilitating the release of gonadotrophin
      releasing hormone (GnRH) and gonadotrophins. CNTF activates membrane receptors
      (CNTF-Rs) composed of one ligand-specific binding subunit, defined CNTFR alpha,
      and two signal transducing subunits, termed leukaemia inhibitory factor receptor
      (LIFR) and gp130. However, it is not clear whether the effects of CNTF on GnRH
      release result from either a direct or an indirect action on GnRH-secreting
      hypothalamic neurones, or from a combination of these events. The hypothesis of a
      direct effect of CNTF was thus tested using the GT1-7 GnRH-secreting cell line.
      CNTF-R expression and CNTF-induced modulation of the Janus kinase (JAK2)-signal
      transducer and activator of transcription 3 (STAT3) pathway and of GnRH release
      were evaluated. GT1-7 cells were found to express CNTFR alpha, LIFR and gp130
      genes, as shown by reverse transcription-polymerase chain reaction analysis, and
      the corresponding proteins, analysed by immunofluorescence and western blot.
      CNTFR alpha, LIFR and gp130 immunoreactive bands had an approximate size of 50,
      190 and 130 kDa, respectively. Treatment of GT1-7 cells with 10(-12) M CNTF for
      15-60 min resulted in a marked and transient increase of STAT3 phosphorylation
      via activation of JAK2. A 30-min exposure of GT1-7 cells to different CNTF
      concentrations increased the accumulation of GnRH into the culture medium, with a
      maximal effect at 10(-11) M. In conclusion, the present results provide new
      information about the regulation of the reproductive axis by CNTF, and suggest
      that it might operate at the hypothalamic level by directly influencing the
      activity of GnRH-secreting neurones, in addition to the possible indirect effects
      via interneurones proposed by previous studies.

PMID- 15869564
TI  - Regulation of peroxisome proliferator activated receptor-gamma in rat pituitary.
AB  - Peroxisome proliferator activated-receptor gamma (PPARgamma) is a member of the
      nuclear receptor superfamily and, in addition to its relation with obesity and
      insulin sensitivity, it has recently been localized in human and mice pituitary,
      indicating a functional significance of PPARgamma in adenopituitary tumours. In
      the present study, we localized the PPARgamma mRNA and protein in different cell
      types of rat pituitary. Moreover, using the real-time polymerase chain reaction,
      we assessed the mRNA expression of PPARgamma in different physiological and
      pathological settings known to be associated with alterations in anterior
      pituitary cell proliferation and/or function. Our experiments have shown that
      PPARgamma mRNA levels were repressed by oestrogen through an oestrogen receptor
      alpha effect. However, PPARgamma protein levels were only modified in males but
      not in females. On the other hand, PPARgamma mRNA expression was increased in
      dwarf rats in comparison with Lewis rats. Finally, nutritional, thyroid status or
      pregnancy did not change PPARgamma expression. Taken together, we provide new
      data regarding the regulation of pituitary PPARgamma mRNA by hormonal and
      metabolic status.

PMID- 15869565
TI  - Expression of pituitary adenylate cyclase activating polypeptide type 1 receptor
      (PAC1R) in the ewe hypothalamus: distribution and colocalization with tyrosine
      hydroxylase-immunoreactive neurones.
AB  - We have examined the distribution of the pituitary adenylate cyclase activating
      polypeptide type I receptor (PAC1R) in the ewe hypothalamus by reverse
      transcription-polymerase chain reaction, in situ hybridization and
      immunohistochemistry. PAC1R mRNA was highly expressed in the mediobasal
      hypothalamus of the ewe, particularly in the arcuate nucleus and ventromedial
      hypothalamus, compared to other hypothalamic regions. Similar results were
      obtained from immunohistochemistry using a specific PAC1R antibody. Intense
      immunolabelling was observed in the arcuate nucleus, external zone of the median
      eminence and ventromedial hypothalamus. Only relatively weak immunolabelling was
      observed in other hypothalamic regions, including the paraventricular nucleus and
      supraoptic nucleus. In the ewe, PACAP acts via the arcuate nucleus to suppress
      prolactin secretion. Therefore we examined whether PAC1R was present on the
      tuberoinfundibular dopamine (TIDA) neurones in this nucleus. Dual
      immunofluorescence labelling for PAC1R and tyrosine hydroxylase revealed that
      21.2 +/- 1.7% of dopaminergic neurones in the arcuate nucleus (A12 cell group)
      also stained for PAC1R. By contrast, other hypothalamic dopaminergic cell groups
      (A11, A13, A14 and A15) exhibited little (< 3%) or no colocalization. Overall,
      our results indicate that, in the ewe hypothalamus, PAC1R is most concentrated in
      the arcuate nucleus, where it is localized on a substantial proportion of
      dopaminergic neurones. These observations, together with previous in vivo
      studies, suggest that PACAP could act directly on TIDA neurones via PAC1R to
      increase dopamine release and consequently inhibit prolactin secretion in the
      sheep.

PMID- 15869566
TI  - Effect of prolyl endopeptidase inhibition on arginine-vasopressin and
      thyrotrophin-releasing hormone catabolism in the rat brain.
AB  - Compound S 17092 is a potent and selective inhibitor of prolyl endopeptidase (EC
      3.4.21.26, PEP) that may be of therapeutic value for the treatment of memory
      impairment associated with neurodegenerative diseases. In the present study, we
      investigated the effects of S 17092 on the catabolism of the promnesic
      neuropeptides thyrotrophin-releasing hormone (TRH) and arginine-vasopressin (AVP)
      in the rat brain. In vitro, bacterial PEP hydrolysed both TRH and AVP, and the
      breakdown of the two peptides was almost completely prevented by 10(-5) M S
      17092. In vivo, a single oral administration of S 17092 provoked a significant
      increase in TRH-like immunoreactivity (TRH-LI) in the cerebral cortex (+63% for a
      10 mg/kg dose and +72% for a 30 mg/kg dose), as well as AVP-LI in the hippocampus
      (+54% for a 30 mg/kg dose), but did not affect TRH-LI in the amygdala nor AVP-LI
      in the cerebral cortex. Chronic administration of S 17092 (10 or 30 mg/kg daily)
      lead to a significant increase in THR-LI in the cerebral cortex (+55% and +56%,
      respectively), but did not modify AVP-LI in the hippocampus, nor in the cerebral
      cortex. These results show that the selective PEP inhibitor S 17092 increases TRH
      and AVP content in discrete regions of the rat brain. The present data suggest
      that the promnesic and antiamnesic effects of S 17092 can be accounted for, at
      least in part, by blockage of AVP and TRH degradation by PEP.

PMID- 15869568
TI  - Thymic transcription of neurohypophysial and insulin-related genes: impact upon T
      cell differentiation and self-tolerance.
AB  - The thymus is the unique lymphoid organ responsible for the generation of a
      diverse repertoire of T lymphocytes that are competent against non self-antigens
      while being tolerant to self-antigens. A vast repertoire of neuroendocrine
      related genes is transcribed in the nonlymphoid cellular compartment of the
      thymus (thymic epithelial cells, dendritic cells and macrophages). The precursors
      encoded by these genes engage two types of interactions with developing T cells
      (thymocytes). First, they are not processed in a classical neuroendocrine way but
      as the source of self-antigens that are presented to pre-T cells by the major
      histocompatibility complex proteins of the thymus. This presentation could be
      responsible for the establishment of central T-cell self-tolerance to
      neuroendocrine functions. Second, they also deliver signal ligands that are able
      to bind to neuroendocrine-type receptors expressed by thymocytes. This
      interaction activates several types of intracellular signalling pathways
      implicated in the developmental process of T lymphocytes. Several experimental
      arguments support a role for thymic dysfunction as a crucial factor in the
      development of organ-specific autoimmune endocrinopathies, such as 'idiopathic'
      central diabetes insipidus and type 1 diabetes mellitus. The rational use of
      tolerogenic neuroendocrine self-antigens for the prevention/treatment of
      autoimmune endocrinopathies is currently under investigation.

PMID- 15869567
TI  - Functional development of the zebrafish pineal gland: light-induced expression of
      period2 is required for onset of the circadian clock.
AB  - In zebrafish, the pineal gland is a photoreceptive organ that contains an
      intrinsic circadian oscillator and exhibits rhythmic arylalkylamine-N
      acetyltransferase (zfaanat2) mRNA expression. In the present study, we
      investigated the role of light and of a clock gene, zperiod2 (zper2), in the
      development of this rhythm. Analysis of zfaanat2 mRNA expression in the pineal
      gland of 3-day-old zebrafish embryos after exposure to different photoperiodic
      regimes indicated that light is required for proper development of the circadian
      clock-controlled rhythmic expression of zfaanat2, and that a 1-h light pulse is
      sufficient to initiate this rhythm. Analysis of zper2 mRNA expression in
      zebrafish embryos exposed to different photoperiodic regimes indicated that zper2
      expression is transiently up-regulated by light but is not regulated by the
      circadian oscillator. To establish the association between light-induced zper2
      expression and light-induced clock-controlled zfaanat2 rhythm, zPer2 knock-down
      experiments were performed. The zfaanat2 mRNA rhythm, induced by a 1-h light
      pulse, was abolished in zPer2 knock-down embryos. These experiments indicated
      that light-induced zper2 expression is crucial for establishment of the clock
      controlled zfaanat2 rhythm in the zebrafish pineal gland.

PMID- 15869569
TI  - Lupus anticoagulants and anticardiolipin antibodies: personal reminiscences, a
      little history, and some random thoughts.

PMID- 15869570
TI  - First isolation of actomyosin from a non-muscle cell: first isolated platelet
      protein.

PMID- 15869571
TI  - Moderate dose oral anticoagulant therapy in patients with the antiphospholipid
      syndrome? Yes.

PMID- 15869572
TI  - Moderate dose oral anticoagulant therapy in patients with the antiphospholipid
      syndrome? No.

PMID- 15869573
TI  - Moderate dose oral anticoagulant therapy in patients with the antiphospholipid
      syndrome? No.

PMID- 15869574
TI  - Oral anticoagulation for the antiphospholipid antibody syndrome: can we now say
      less is more?

PMID- 15869575
TI  - A randomized clinical trial of high-intensity warfarin vs. conventional
      antithrombotic therapy for the prevention of recurrent thrombosis in patients
      with the antiphospholipid syndrome (WAPS).
AB  - BACKGROUND: The optimal intensity of oral anticoagulation for the prevention of
      recurrent thrombosis in patients with antiphospholipid antibody syndrome is
      uncertain. Retrospective studies show that only high-intensity oral
      anticoagulation [target international normalized ratio (INR) >3.0] is effective
      but a recent randomized clinical trial comparing high (INR range 3.0-4.0) vs.
      moderate (INR 2.0-3.0) intensities of anticoagulation failed to confirm this
      assumption. METHODS: We conducted a randomized trial in which 109 patients with
      antiphospholipid syndrome (APS) and previous thrombosis were given either high
      intensity warfarin (INR range 3.0-4.5, 54 patients) or standard antithrombotic
      therapy (warfarin, INR range 2.0-3.0 in 52 patients or aspirin alone, 100 mg day(
      1) in three patients) to determine whether intensive anticoagulation is superior
      to standard treatment in preventing symptomatic thromboembolism without
      increasing the bleeding risk. RESULTS: The 109 patients enrolled in the trial
      were followed up for a median time of 3.6 years. Mean INR during follow-up was
      3.2 (SD 0.6) in the high-intensity warfarin group and 2.5 (SD 0.3) (P < 0.0001)
      in the conventional treatment patients given warfarin. Recurrent thrombosis was
      observed in six of 54 patients (11.1%) assigned to receive high-intensity
      warfarin and in three of 55 patients (5.5%) assigned to receive conventional
      treatment [hazard ratio for the high intensity group, 1.97; 95% confidence
      interval (CI) 0.49-7.89]. Major and minor bleeding occurred in 15 patients (two
      major) (27.8%) assigned to receive high-intensity warfarin and eight (three
      major) (14.6%) assigned to receive conventional treatment (hazard ratio 2.18; 95%
      CI 0.92-5.15). CONCLUSIONS: High-intensity warfarin was not superior to standard
      treatment in preventing recurrent thrombosis in patients with APS and was
      associated with an increased rate of minor hemorrhagic complications.

PMID- 15869576
TI  - The skinny on treatment of venous thromboembolism in obesity.

PMID- 15869577
TI  - The influence of extreme body weight on clinical outcome of patients with venous
      thromboembolism: findings from a prospective registry (RIETE).
AB  - BACKGROUND: Data evaluating the safety of using weight-based dosing of low
      molecular-weight heparin (LMWH) in either underweight or obese patients with
      venous thromboembolism (VTE) are limited. Thus, recommendations based on evidence
      from clinical trials might not be suitable for patients with extreme body weight.
      PATIENTS AND METHODS: Patients with objectively confirmed, symptomatic acute VTE
      are consecutively enrolled into the Registro Informatizado de la Enfermedad
      TromboEmbolica (RIETE) registry. For this analysis, data from patients in the
      following ranges of body weight were examined: <50, 50-100, and >100 kg. Patient
      characteristics, underlying conditions, treatment schedules and clinical outcomes
      during the first 15 days of treatment were compared. RESULTS: As of August 2004,
      8845 patients with acute VTE were enrolled from 94 participating centers. Of
      these, 169 (1.9%) weighed <50 kg, 8382 (95%) weighed 50-100 kg and 294 (3.3%)
      weighed >100 kg. Patients weighing <50 kg were more commonly females, were taking
      non-steriodal antiinflammatory drugs (NSAIDs), and had severe underlying diseases
      more often than patients weighing 50-100 kg. Their incidence of overall bleeding
      complications was significantly higher than in patients weighing 50-100 kg (odds
      ratio 2.2; 95% CI: 1.2-4.0). Patients weighing >100 kg were younger, most
      commonly males, and had cancer less often than those weighing 50-100 kg.
      Incidences of recurrent VTE, fatal pulmonary embolism or major bleeding
      complications were similar in both groups. CONCLUSIONS: Patients with VTE
      weighing <50 kg have a significantly higher rate of bleeding complications. The
      clinical outcome of patients weighing over 100 kg was not significantly different
      from that in patients weighing 50-100 kg.

PMID- 15869578
TI  - Life without histidine-rich glycoprotein: modulation of the hemostatic balance
      revisited.

PMID- 15869579
TI  - Enhanced blood coagulation and fibrinolysis in mice lacking histidine-rich
      glycoprotein (HRG).
AB  - Histidine-rich glycoprotein (HRG) is a serum protein belonging to the cystatin
      superfamily. HRG may play a regulatory role in hemostasis and innate immunity.
      However, this role is uncertain because of a lack of rigorous testing in an
      animal model. We generated mice lacking the translation start point of exon 1 of
      the Hrg gene, effectively resulting in a null mutation (Hrg-/-). The mice were
      viable and fertile but had no HRG in their blood. Antithrombin activity in the
      plasma of Hrg-/- mice was higher than in the plasma of heterozygous Hrg+/- or
      wild-type Hrg+/+ mice. The prothrombin time was shorter in Hrg-/- mice than in
      Hrg+/- and Hrg+/+ mice. Bleeding time after tail tip amputation in Hrg-/- mice
      was shorter than in Hrg+/+ mice. The spontaneous fibrinolytic activity in clotted
      blood of Hrg-/- mice was higher than in Hrg+/+ mice. These findings suggest that
      HRG plays a role as both an anticoagulant and an antifibrinolytic modifier, and
      may regulate platelet function in vivo.

PMID- 15869580
TI  - Vitronectin: back into the spotlight.

PMID- 15869581
TI  - Cell-derived microparticles: 'Miniature envoys with many faces'.

PMID- 15869582
TI  - Cell-derived microparticles contain caspase 3 in vitro and in vivo.
AB  - BACKGROUND: Microparticles (MP) from endothelial cells (endothelial
      microparticles; EMP) circulate in disease states, but the processes such as
      apoptosis or cell activation underlying their release are unclear. OBJECTIVES: We
      investigated whether adherent (viable) or detached (apoptotic) endothelial cells
      are the possible source of EMP in vitro, i.e. under control and interleukin (IL)
      1alpha activation conditions, and in vivo. METHODS: Adherent and detached
      endothelial cells, and EMP, were isolated from human umbilical vein endothelial
      cell cultures (n = 6), treated without or with IL-1alpha (5 ng mL(-1); 24 h).
      Cell fractions were analyzed by flow cytometry for annexin V binding, propidium
      iodide (PI) and caspase 3 staining (n = 3). Caspase 3 in EMP was studied using
      Western blot (n = 6) and flow cytometry (n = 6). Plasma from healthy subjects and
      systemic lupus erythematosus patients (both n = 3) were analyzed for caspase 3
      containing (E)MP. RESULTS: Detached but not adherent cells double-stained for
      annexin V and PI, confirming the apoptotic conditions of the detached cells and
      the viable nature of the adherent cells. Caspase 3 was solely present in the
      detached cells and procaspase 3 in the adherent cells. Caspase 3 was present in
      EMP from both control and IL-1alpha-treated cultures. Counts of EMP and detached
      cells, but not adherent cells, highly correlated (r = 0.959, P < 0.0001). In vivo
      circulating MP from nucleated (endothelial cells, monocytes) and anucleated cells
      (platelets, erythrocytes) contained caspase 3. CONCLUSIONS: EMP contain caspase 3
      and may be mainly derived from detached (apoptotic) endothelial cells in vitro.
      The presence of caspase 3 in MP from anucleated cell types, however, suggests
      that its presence may not necessarily be related to apoptosis in vivo but may be
      associated with caspase 3 activation unrelated to apoptosis.

PMID- 15869583
TI  - Negative impact of depression on outcomes in patients with coronary artery
      disease: mechanisms, treatment considerations, and future directions.
AB  - Depressive symptoms are common in coronary artery disease (CAD) patients, and are
      associated with increased cardiac risk. Although an important relation exists
      between depression and CAD prognosis, the underlying pathophysiological
      mechanisms are poorly understood. Additionally, evidence including the recently
      published ENRICHD (Enhancing Recovery in Coronary Heart Disease Patients) trial
      suggests that depression treatments do not lower recurrent cardiac risk. The
      reason for the observed lack of benefit with depression treatment in CAD patients
      is unclear. In this review, we discuss the impact of depression in CAD patients,
      the possible mechanisms involved, the studies that have examined the effects of
      psychological and antidepressant therapies on recurrent cardiac events, and the
      direction that future research should take.

PMID- 15869584
TI  - A model-based algorithm for the monitoring of long-term anticoagulation therapy.
AB  - It has been shown that computerized algorithms for the prescription of coumarin
      derivates can improve the quality of long-term anticoagulation treatment. These
      algorithms are usually based on an empiric relationship between dosage and
      International Normalized Ratio and do not quantify the delaying effect of the
      drug's pharmacokinetics or the effect of alternating doses that are used to
      approximate a certain average dosage. Our objective was to develop a mathematical
      model that takes into account these effects and to develop a new algorithm based
      on this model that can be used to further optimize the quality of long-term
      anticoagulation treatment. We simplified a general model structure that was
      proposed by Holford in 1986 so that the parameters can be estimated using data
      that are available during long-term anticoagulation treatment. The constant
      parameters in the model were estimated separately for phenprocoumon and
      acenocoumarol using data from 1279 treatment courses from three different
      anticoagulation clinics in the Netherlands. The only variable parameter in the
      model is the sensitivity of the patient, which is estimated during the course of
      each treatment. A total of 194 dosage and appointment intervals that were
      proposed by the new algorithm were scored as 'good', 'acceptable', or 'bad' by
      two dosing experts. One hundred and seventy-eight (91.8%) proposals were
      considered good by at least one expert and bad by none. In 39 cases the experts
      disagreed. We believe that this algorithm will allow further improvement of
      anticoagulation treatments.

PMID- 15869585
TI  - Safety, pharmacokinetics, and immunogenicity of single-dose rFXIII administration
      to healthy volunteers.
AB  - BACKGROUND: Factor XIII (FXIII) is a transglutaminase that cross-links fibrin and
      other proteins to improve clot strength and resistance to fibrinolysis. Both
      congenital and acquired FXIII deficiency may result in a bleeding diathesis, and
      plasma-derived FXIII has been used to treat many of these clinical conditions.
      OBJECTIVES: A clinical study was designed and performed to evaluate the safety,
      pharmacokinetics, and immunogenicity of recombinant FXIII (rFXIII) administration
      to healthy adult volunteers. PATIENTS AND METHOD: Fifty healthy adult volunteers
      were enrolled in this randomized, double-blinded, placebo-controlled study. A
      single dose of rFXIII, ranging from 2 U kg(-1) to 50 U kg(-1), or placebo was
      administered. Safety was evaluated by capturing adverse events, clinical safety
      laboratory studies, and clinical score for deep venous thrombosis. Blood samples
      were taken for pharmacokinetic and immunogenicity analysis throughout the 28-day
      follow-up period. RESULTS: Recombinant FXIII was well tolerated, with no serious
      adverse events or dose-related toxicities. Following a single i.v. injection of
      50 U kg(-1) rFXIII, the estimated terminal half-life was 270-320 h, the volume of
      distribution ranged from 40 to 75 mL kg(-1), and FXIII activity increased 1.77%
      per 1 U kg(-1) rFXIII administered. Increase in circulating A2B2 and decrease in
      free FXIII-B subunit indicate in vivo formation of FXIII heterotetramer. An
      immunogenic response to rFXIII or yeast, the production host, was not observed.
      CONCLUSIONS: Recombinant FXIII was well tolerated at doses of up to 50 U kg(-1)
      in healthy adult volunteers. The safety, pharmacological and immunological
      profile of rFXIII suggests it should be studied in patients with congenital FXIII
      deficiency as well as evaluated as a systemic hemostat in patients with acquired
      FXIII deficiency or hemorrhage.

PMID- 15869586
TI  - Cardiovascular and thrombophilic risk factors for idiopathic sudden sensorineural
      hearing loss.
AB  - BACKGROUND: In recent years there has been a significant increase in the
      diagnosis of sudden sensorineural hearing loss (SSHL) in western, countries with
      an incidence of 20 of 100,000 people affected every year. No clear causes for
      this disease have been found thus far, but cochlear ischemia has been
      hypothesized in patients in whom an infectious episode or acoustic neurinoma have
      been excluded. OBJECTIVES: The aim of this case-control study was to investigate
      a number of acquired and inherited thrombophilic risk factors [antithrombin,
      protein C and S; factor V (FV) Leiden, FII polymorphism; lupus anticoagulant
      (LA); anticardiolipin (aCL) antibodies; fasting homocysteine (Hcy);
      lipoprotein(a) (Lp(a)); plasminogen activator inhibitor-1 (PAI-1)] in addition to
      cardiovascular risk factors in patients with idiopathic SSHL (ISSHL). PATIENTS
      AND METHODS: We investigated 155 patients (67 male/88 female; age: 55 (range 19
      79 years) with a diagnosis of ISSHL within 30 days from the onset of symptoms,
      and 155 controls (67 male/88 female; age 54 (range 19-78 years). Fasting Hcy
      levels were significantly higher in patients than in controls [11.6 (6.7-60)
      micromol/L vs. 8.7 (5.0-24) micromol/L] as well as PAI-1 levels [19 (2-95) mg/dL
      vs. 14.5 (4.0-87) mg/dL]. Lupus anticoagulant was present in 13 of 155 (8.4%)
      patients; 20 patients (12.9%) had positivity of aCL (four IgM and 16 IgG). In no
      patient was a deficiency of physiological clotting inhibitors antithrombin,
      protein C and protein S found. No significant differences between patients and
      controls were observed for Lp(a) plasma levels [111 (1-1146) mg/L vs. 103 (11
      695) mg/L] and for the presence of FV Leiden (4.5% vs. 4.5%) and FII variant
      G20210A (3.8% vs. 3.2%). RESULTS AND CONCLUSIONS: Independent risk factors for
      ISSHL at the multivariate analysis (adjusted for age, sex and the traditional
      cardiovascular risk factors) were the positivity of aCL: OR 5.6 (95% CI 2.0
      15.3); cholesterol levels within the second and third tertiles (with respect to
      the first tertile): T2 = OR 4.8 (95% CI 1.9-12.6)/T3 = OR 19 (95% CI 7-50.1); PAI
      1 and Hcy levels within the third tertile (with respect to the first tertile): OR
      20 (95% CI 7.8-78) and OR 4.0 (95% CI 2.0-8.1), respectively. These preliminary
      data suggest that hypercholesterolemia, hyperhomocysteinemia, elevated PAI-1
      levels and anticardiolipin antibodies are associated with ISSHL, so indirectly
      supporting the hypothesis of a vascular occlusion in the pathogenesis of the
      disease.

PMID- 15869587
TI  - Decreased plasma sensitivity to activated protein C by oral contraceptives is
      associated with decreases in plasma glucosylceramide.
AB  - Oral contraceptive (OC) use increases venous thrombosis (VTE) risk and causes
      activated protein C (APC) resistance. Plasma glucosylceramide (GlcCer) deficiency
      is associated with VTE and GlcCer functions as an APC anticoagulant cofactor.
      Because estradiol decreases GlcCer in cultured cells, we hypothesized OC use
      would decrease plasma GlcCer and contribute to APC resistance. In a pilot study,
      seven female adults alternatively took second and third generation OCs and plasma
      samples were analyzed for GlcCer using high performance liquid chromatography and
      for APC sensitivity using modified prothrombin time assays. Second and third
      generation OC usage decreased the APC sensitivity ratio by 8.1% +/- 4.7% (P =
      0.004) and 11.7% +/- 8.2% (P = 0.013) and plasma GlcCer levels by 10.1% +/- 6.8%
      (P = 0.008) and 11.0% +/- 5.1% (P = 0.002), respectively. The plasma GlcCer level
      correlated with the sensitivity of plasma to APC (P = 0.017, r = 0.51, n = 21
      plasma samples). Thus, both second and third generation OC usage decreased plasma
      GlcCer which could cause a reduction in the plasma sensitivity to APC/protein S,
      thereby potentially increasing VTE risk.

PMID- 15869588
TI  - Relation between quality of anticoagulant treatment and the development of the
      postthrombotic syndrome.
AB  - BACKGROUND: About 30% of patients with an episode of adequately treated deep
      venous thrombosis (DVT) develop the postthrombotic syndrome (PTS) within 2 years.
      During treatment with vitamin K antagonists (VKA) patients spend only 60% of time
      between an International Normalized Ratio (INR) of 2.0 and 3.0. We hypothesized
      that patients who spend a large amount of their time beneath this range will have
      an increased risk of the PTS. OBJECTIVE: To investigate the relation between the
      quality of anticoagulant therapy with VKA and the risk of the development of the
      PTS. METHODS: The time spent beneath the therapeutic range was calculated for
      patients with a first episode of DVT, who were treated with VKA for at least 3
      months. At follow-up assessments for a maximum of 5 years, presence and severity
      of signs and symptoms of PTS were recorded. RESULTS: A total of 244 patients,
      with a median duration of follow-up of 4.9 years were included for analysis. Of
      these, 81 patients (33%) developed the PTS. The multivariate model showed that
      patients who spend more than 50% of their time beneath an INR level of 2.0 are at
      higher risk for PTS [odds ratio (OR): 2.71, 95% CI: 1.44-5.10]. CONCLUSIONS: Low
      quality treatment with VKA, which is a common condition, is related to the
      occurrence of the PTS in patients with DVT. Strategies aimed at improving the
      quality of long-term anticoagulation might have the potential to reduce the
      incidence of this complication.

PMID- 15869589
TI  - Does the type of hormone replacement therapy influence the risk of deep vein
      thrombosis? A prospective case-control study.
AB  - BACKGROUND: Although hormone replacement therapy (HRT) is associated with an
      increased risk of deep vein thrombosis (DVT), it is not clear if the risk differs
      in users of combined estrogen-progestin HRT and estrogen-only HRT. METHODS: We
      prospectively studied postmenopausal women with suspected DVT in whom HRT use
      status was ascertained and who subsequently had objective diagnostic testing to
      confirm or exclude DVT. Cases were patients with idiopathic DVT, in whom there
      were no DVT risk factors, and controls were patients without DVT, in whom there
      were also no DVT risk factors. The risk of DVT was determined in users of
      estrogen-progestin HRT and estrogen-only HRT by comparing the prevalence of
      current HRT use in cases with idiopathic DVT and controls without DVT (reference
      group). Multivariable regression analysis was done to adjust for factors that
      might confound an association between HRT use and the risk of DVT. RESULTS: One
      thousand one hundred and sixty-eight postmenopausal women with suspected DVT were
      assessed, from whom 95 cases of idiopathic DVT and 610 controls without DVT and
      no DVT risk factors were identified. Estrogen-only HRT was associated with an
      increased risk for DVT that was not statistically significant [odds ratio (OR) =
      1.22; 95% confidence interval (CI) 0.57, 2.61]. Estrogen-progestin HRT was
      associated with a greater than 2-fold increased risk for DVT (OR = 2.70; 95% CI
      1.44, 5.07). CONCLUSION: The risk of developing DVT may be higher in users of
      combined estrogen-progestin HRT than in users of estrogen-only HRT.

PMID- 15869590
TI  - Risk of pregnancy-associated recurrent venous thromboembolism in women with a
      history of venous thrombosis.
AB  - BACKGROUND: Limited data exist on the risk of pregnancy-associated venous
      thromboembolism (VTE) in women with a history of VTE. OBJECTIVE: To evaluate the
      risk of recurrent pregnancy-associated thrombosis in women with previous VTE in a
      large retrospective cohort study. PATIENTS AND METHODS: One hundred and fifty
      nine women with at least one pregnancy (293 pregnancies in total) after a VTE
      were included into the study. The patients underwent a standardized interview on
      their history of thrombosis and pregnancy-associated complications. RESULTS:
      Eight recurrent events occurred during 197 pregnancies without thrombosis
      prophylaxis. The probability of VTE during pregnancy without thrombosis
      prophylaxis was 6.2% (95% confidence interval 1.6-10.9%). The risk was constant
      over the whole period of pregnancy. Of the eight women with VTE during pregnancy
      four had heterozygous FV:R506Q, two in combination with hyperhomocysteinemia. No
      VTE occurred during 87 pregnancies with thrombosis prophylaxis. In the postpartum
      period 15 VTEs occurred, two of 83 (2.4%) after pregnancy termination, one of 53
      (1.9%) after miscarriage, three of 10 (30%) after stillbirth and nine of 138
      (6.5%) after live birth. CONCLUSIONS: Without thrombosis prophylaxis the risk for
      recurrent symptomatic VTE is substantial during the whole period of pregnancy in
      women with previous VTE. The majority of events occurred after delivery,
      reflecting the very high risk during the postpartum period. Prospective and
      comparative trials to ascertain efficacy and safety of prophylactic heparin are
      urgently needed.

PMID- 15869591
TI  - Poor anticoagulation quality in the first 3 months after unprovoked venous
      thromboembolism is a risk factor for long-term recurrence.
AB  - BACKGROUND AND AIM: Several factors are associated with an increased risk of
      recurrent venous thromboembolism (VTE). The aim of the study was to investigate
      whether the quality of oral anticoagulation therapy (OAT) is a long-term risk
      factor for recurrence of VTE after OAT interruption. METHODS AND RESULTS: A total
      of 297 patients (170 males) with a recent acute unprovoked VTE episode were
      prospectively monitored during OAT in our anticoagulation clinic and followed up
      for 21 months after OAT interruption. Recurrent events were recorded in 42
      subjects for 493 years of follow-up [14.1% of patients; 8.5% patient-years (pt
      y)] after OAT withdrawal. The rate of recurrence was not correlated to OAT
      duration. Subjects experiencing recurrence after OAT interruption had spent
      significantly more time at markedly subtherapeutic international normalized ratio
      (INR) levels (<1.5) and less time within the therapeutic range (2.0-3.0 INR)
      during OAT. Relative risk (RR) of recurrence was significantly higher [2.77 (95%
      confidence interval (CI) 1.49-5.18; P = 0.001) and 2.70 (95% CI 1.39-5.25; P =
      0.003) at univariate and multivariate analysis, respectively] in those who spent
      more time (upper quintile) at INR values <1.5, being especially evident in the
      first 90 days of OAT. RR was significantly higher at univariate [2.05 (95% CI
      1.07-3.96; P = 0.031)] but not at multivariate [1.98 (95% CI 0.98-4.0; P =
      0.056)] analysis when the entire OAT period was considered. Subjects in the upper
      quintile of time spent at INR values <1.5 had significantly higher D-dimer values
      when OAT was stopped and after 3 months. CONCLUSIONS: The amount of time that
      subjects with an acute unprovoked VTE event spend at near-normal INR values
      (<1.5) during the first 3 months of treatment is associated with higher D-dimer
      values measured during OAT and after its interruption and is a significant risk
      factor for late VTE recurrence.

PMID- 15869592
TI  - Dose-response study of recombinant human soluble thrombomodulin (ART-123) in the
      prevention of venous thromboembolism after total hip replacement.
AB  - BACKGROUND: Recombinant human soluble thrombomodulin (ART-123) is composed of the
      active, extracellular, domain of thrombomodulin. ART-123 binds to thrombin and
      this complex converts protein C into the natural anticoagulant activated protein
      C. This study was performed to identify an effective and safe dose of ART-123 for
      prevention of venous thromboembolism after elective, unilateral total hip
      replacement. METHODS AND RESULTS: An open-label, sequential, dose-ranging study
      was performed in which 312 patients received either 0.3 mg kg(-1) or 0.45 mg kg(
      1) of ART-123, subcutaneously, 2-4 h after surgery (day 1). Those who received
      0.3 mg kg(-1) were given a second dose of 0.3 mg kg(-1) on day 6, and the first
      29 of these patients also used intermittent pneumatic compression devices. Those
      who received 0.45 mg kg(-1) were not given a second dose. Primary efficacy
      outcome was all deep vein thrombosis on mandatory bilateral venography performed
      on day 9 +/- 2 and symptomatic venous thromboembolism up to day 11. Primary
      safety outcome was major bleeding up to day 11. Among patients who did not use
      intermittent pneumatic compression, venous thromboembolism occurred in 3.4% of
      116 evaluable patients in the 0.3 mg kg(-1) group and 0.9% of 111 patients in the
      0.45 mg kg(-1) group. Major bleeding occurred in 1.4% of 139 patients in the 0.3
      mg kg(-1) group and 6.3% of 144 patients in the 0.45 mg kg(-1) group. CONCLUSION:
      ART-123 is a highly effective antithrombotic agent that should be directly
      compared with current methods of prophylaxis in patients who have major
      orthopedic surgery.

PMID- 15869593
TI  - The antigenic binding site(s) of antibodies to factor XII associated with the
      antiphospholipid syndrome.
AB  - Phospholipid binding proteins, including factor XII (FXII), are known to be
      targeted by antiphospholipid antibodies (aPA). Factor XII antibodies (FXIIab)
      have been described in some patients with the antiphospholipid syndrome (APS) and
      have been shown to lead to reduced levels of FXII. The antigenic binding site(s)
      and the pathophysiological effects of FXIIab are unknown. In an attempt to
      elucidate the binding site of these antibodies, immobilized plasma kallikrein was
      used to cleave FXII into its 52-kDa heavy-chain (HCFXII) and 28-kDa light-chain
      (LCFXII) components. Plasma samples from 12 female patients with definite APS and
      FXIIab were investigated for the presence of antibodies to FXII, HCFXII and
      LCFXII. All but one patient's plasma reacted to FXII, HCFXII and LCFXII in a
      similar manner. One patient gave markedly reduced positivity to HCFXII and
      LCFXII, suggesting that the FXIIab in this patient had a higher affinity for the
      intact FXII molecule. To further investigate the antigenic binding site(s) of
      FXII, 150 biotinylated peptides of the known FXII sequence were synthesized using
      a Multipin(TM) peptide synthesis procedure. The IgG and IgM fractions of the 12
      patients' plasma were purified by affinity chromatography. The synthesized
      peptides were captured on streptavidin plates and individual patients' purified
      FXIIab assayed against the peptides in a modified enzyme-linked immunosorbent
      assay (ELISA). Two regions were identified as possible antigenic binding site(s)
      for FXIIab: one in the growth factor domain and the other in the catalytic
      domain.

PMID- 15869594
TI  - Soluble thrombomodulin activity and soluble thrombomodulin antigen in plasma.
AB  - Endothelial cell membrane-bound thrombomodulin (TM) plays a critical role as a
      cofactor in the protein C pathway, important in regulating coagulation as well as
      inflammation. Heterogeneous soluble TM fragments circulate in the plasma and are
      found at increased levels in various diseases such as cardiovascular disease and
      diabetes, and in ischemic and/or inflammatory endothelial injuries. The
      anticoagulant function of these soluble fragments has not been measured in
      healthy individuals or in patients. Using an immobilized monoclonal antibody
      against TM and a microtiter plate format, an assay was designed to capture the
      soluble TM fragments in plasma and measure their cofactor activity in the
      thrombin-mediated activation of protein C. In addition, soluble TM antigen levels
      were measured by enzyme-linked immunosorbent assay. Both assays were used to
      investigate a group of healthy blood donors. TM fragments released into plasma
      were shown to retain significant cofactor activity, and reference intervals for
      healthy men and women were established. Furthermore, a statistically significant
      correlation was observed between soluble TM antigen levels and soluble TM
      cofactor activity. This notwithstanding, soluble TM activity only accounted for a
      minor part of all variation in soluble TM antigen levels (R2 = 22% in men and R2
      = 16% in women).

PMID- 15869595
TI  - Functional analysis of recombinant Bbeta15C and Bbeta15A fibrinogens demonstrates
      that Bbeta15G residue plays important roles in FPB release and in lateral
      aggregation of protofibrils.
AB  - BACKGROUND AND OBJECTIVES: Analysis of dysfibrinogens has improved our
      understanding of molecular defects and their effects on the function of intact
      fibrinogen. To eliminate the influence of plasma heterozygous molecules, we
      synthesized and analyzed recombinant-variant fibrinogens. METHODS: We synthesized
      two recombinant-variant fibrinogens with a single amino acid substitution at the
      15Gly residue in the Bbeta-chain: namely, Bbeta15Cys and Bbeta15Ala. RESULTS:
      Western blotting analysis of purified fibrinogen revealed the existence of a
      small amount of a dimeric form only for Bbeta15Cys fibrinogen. For Bbeta15Cys
      fibrinogen, functional analysis indicated (a) no thrombin-catalyzed
      fibrinopeptide B (FPB) release and (b) markedly impaired lateral aggregation in
      thrombin- and reptilase-catalyzed fibrin polymerizations. For Bbeta15Ala
      fibrinogen, such analysis indicated slight impairments of both thrombin-catalyzed
      FPB release and lateral aggregation in thrombin-catalyzed fibrin polymerization,
      but nearly normal lateral aggregation in reptilase-catalyzed fibrin
      polymerization. These impaired lateral aggregations were accompanied by thinner
      fibrin fiber diameters (determined by scanning electron microscopy of the
      corresponding fibrin clots). CONCLUSION: We conclude that a region adjacent to
      Bbeta15Gly plays important roles in lateral aggregation not only in desA fibrin
      polymerization, but also in desAB fibrin polymerization, and we speculate that
      the marked functional differences between Bbeta15A and Bbeta15C fibrinogens in
      FPB release and fibrin polymerization might not only be due to the presence of a
      substituted cysteine residue in Bbeta15C fibrinogen, but also to the existence of
      disulfide-bonded forms. Finally, our data indicate that the Bbeta15Gly residue
      plays important roles in FPB release and lateral aggregation of protofibrils.

PMID- 15869596
TI  - Identification and removal of a promiscuous CD4+ T cell epitope from the C1
      domain of factor VIII.
AB  - BACKGROUND: The development of inhibitors in hemophiliacs is a severe
      complication of factor VIII (FVIII) replacement therapy and is a process driven
      by FVIII specific T helper cells. OBJECTIVES: To finely map T cell epitopes
      within the whole FVIII protein in order to investigate the possibility of
      engineering FVIII variants with reduced propensity for inhibitor development.
      PATIENTS AND METHODS: T cell lines were generated from five patients with severe
      hemophilia who had developed inhibitors, and were screened for T cell
      proliferation against pools of overlapping peptides spanning the entire B domain
      deleted (BDD) FVIII sequence. Positive peptide pools were decoded by screening
      individual peptides against the T cell lines. Positive peptides, and mutants
      thereof, were tested for their ability to bind major histocompatibility complex
      (MHC) Class II and stimulate T cell proliferation in a panel of healthy donors.
      The activities of the corresponding mutant proteins were assessed via chromogenic
      assay. RESULTS: One peptide, spanning FVIII amino acids 2098-2112, elicited a
      vigorous response from one hemophiliac donor, induced strong T cell responses in
      the panel of healthy donors and bound to a number of HLA-DR alleles. Mutations
      were made in this peptide that removed its ability to stimulate T cells of
      healthy donors and to bind to MHC Class II while retaining full activity when
      incorporated into a mutant BDD-FVIII protein. CONCLUSIONS: Fine T cell epitope
      mapping of the entire FVIII protein is feasible, although challenging, and this
      knowledge may be used to create FVIII variants which potentially have reduced
      immunogenicity.

PMID- 15869597
TI  - Post-transcriptional regulation of plasminogen activator inhibitor-1 by
      intracellular iron in cultured human lung fibroblasts--interaction of an 81-kDa
      nuclear protein with the 3'-UTR.
AB  - The proteinase inhibitor, type-1 plasminogen activator inhibitor (PAI-1), is a
      major regulator of the plasminogen activator system involved in plasmin formation
      and fibrinolysis. The present study explores the effects of intracellular iron on
      the expression of PAI-1 and associated cell-surface plasmin activity in human
      lung fibroblasts; and reports the presence of a novel iron-responsive protein.
      ELISA revealed a dose-dependent increase in PAI-1 antigen levels expressed in the
      conditioned medium of cells treated with deferoxamine, in the three cell lines
      studied. A concomitant increase in mRNA levels was also observed by Northern
      analyses. Presaturation with ferric citrate quenched the effect of deferoxamine.
      Experiments with transcription and translation inhibitors on TIG 3-20 cells
      demonstrated that intracellular iron modulated PAI-1 expression at the post
      transcriptional level with the requirement of de-novo protein synthesis.
      Electrophoretic mobility shift assay and UV crosslinking assays revealed the
      presence of an approximately 81-kDa nuclear protein that interacted with the 3'
      UTR of PAI-1 mRNA in an iron-sensitive manner. Finally, we demonstrated that the
      increased PAI-1 is functional in suppressing cell-surface plasmin activity, a
      process that can affect wound healing and tissue remodeling.

PMID- 15869598
TI  - In vivo and in vitro analysis of the human tissue-type plasminogen activator gene
      promoter in neuroblastomal cell lines: evidence for a functional upstream kappaB
      element.
AB  - Besides its well-established role in wound healing and fibrinolysis, tissue-type
      plasminogen activator (t-PA) has been shown to contribute to cognitive processes
      and memory formation within the central nervous system, and to promote glutamate
      receptor-mediated excitotoxicity. The t-PA gene is expressed and regulated in
      neuronal cells but the regulatory transcriptional processes directing this
      expression are still poorly characterized. We have used DNase I-hypersensitivity
      mapping and in vivo foot printing to identify putative regulatory elements and
      transcription factor binding sites in two human neuroblastomal (KELLY and SK-N
      SH) and one human glioblastomal (SNB-19) cell lines. Hypersensitive sites were
      found in the proximal promoter region of all cell lines, and within the first
      exon for KELLY and SNB-19 cells. Mapping of methylation-protected residues in
      vivo detected a cluster of protected residues corresponding to a cAMP response
      element (CRE) and Sp1 sites in the proximal promoter previously shown to be
      essential for basal expression in other cell types. Protected residues were also
      found at other sites, notably a kappaB element at position bp -3081 to -3072 that
      was partly protected in KELLY and SNB-19 cells. Analysis of transfected reporter
      constructs in KELLY and SNB-19 cells confirmed that this particular element is
      functionally significant in the transactivation of the t-PA promoter in both cell
      types. This study defines, by in vivo and in vitro methods, a previously
      undescribed kappaB site in the t-PA gene promoter that influences t-PA expression
      in neuronal cells.

PMID- 15869599
TI  - The role of plasminogen activator inhibitor type 1 in the inflammatory response
      to local tissue injury.
AB  - BACKGROUND: The plasma levels of the plasminogen activator-inhibitor type 1 (PAI
      1) are consistently elevated in patients with sterile tissue injury, often
      accompanied by a systemic acute phase protein response. It remains unknown,
      however, whether and to what extent PAI-1 affects the host response to trauma.
      METHODS AND RESULTS: By using the well-established murine model of turpentine
      induced tissue injury we compared local and systemic inflammatory responses in
      PAI-1 gene-deficient (PAI-1-/-) and normal wild-type (Wt) mice. Subcutaneous
      turpentine injection elicited strong increases in PAI-1 protein concentration in
      plasma and at the site of injury, but not in liver. PAI-1 mRNA was locally
      increased and expressed mainly by macrophages and endothelial cells. PAI-1
      deficiency greatly enhanced the early influx of neutrophils to the site of
      inflammation, which was associated with increased edema and necrosis at 8 h after
      injection. Furthermore, PAI-1-/- mice showed a reduced early interleukin (IL)-6
      induction with subsequently lower acute phase protein levels and a much slower
      recovery of body weight loss. CONCLUSION: These findings suggest that PAI-1 is
      not merely a marker of tissue injury but plays a functional role in the local and
      systemic host response to trauma.

PMID- 15869600
TI  - Altered cytoskeleton organization in platelets from patients with MYH9-related
      disease.
AB  - MYH9-related disease (MYH9-RD) is an autosomal dominant disorder deriving from
      mutations in the MYH9 gene encoding for the heavy chain of non-muscle myosin IIA,
      and characterized by thrombocytopenia and giant platelets. Isoform IIA of myosin
      is the only one expressed in platelets, but the possibility that MYH9 mutations
      affect the organization of contractile structures in these blood elements has
      never been investigated. In this work we have analyzed the composition and the
      agonist-induced reorganization of the platelet cytoskeleton from seven MYH9-RD
      patients belonging to four different families. We found that an increased amount
      of myosin was constitutively associated with actin in the cytoskeleton of resting
      MYH9-RD platelets. Upon platelet stimulation, an impaired increase in the total
      cytoskeletal proteins was observed. Moreover, selected membrane glycoproteins,
      tyrosine kinases, and small GTPases failed to interact with the cytoskeleton in
      agonist-stimulated MYH9-RD platelets. These results demonstrate for the first
      time that mutations of MYH9 result in an alteration of the composition and
      agonist-induced reorganization of the platelet cytoskeleton. We suggest that
      these abnormalities may represent the biochemical basis for the previously
      reported functional alterations of MYH9-RD platelets, and for the abnormal
      platelet formation from megakaryocytes, resulting in thrombocytopenia and giant
      platelets.

PMID- 15869601
TI  - Lipid rafts are required in Galpha(i) signaling downstream of the P2Y12 receptor
      during ADP-mediated platelet activation.
AB  - ADP is important in propagating hemostasis upon its secretion from activated
      platelets in response to other agonists. Lipid rafts are microdomains within the
      plasma membrane that are rich in cholesterol and sphingolipids, and have been
      implicated in the stimulatory mechanisms of platelet agonists. We sought to
      determine the importance of lipid rafts in ADP-mediated platelet activation via
      the G protein-coupled P2Y1 and P2Y12 receptors using lipid raft disruption by
      cholesterol depletion with methyl-beta-cyclodextrin. Stimulation of cholesterol
      depleted platelets with ADP resulted in a reduction in the extent of aggregation
      but no difference in the extent of shape change or intracellular calcium release.
      Furthermore, repletion of cholesterol to previously depleted membranes restored
      ADP-mediated platelet aggregation. In addition, P2Y12-mediated inhibition of cAMP
      formation was significantly decreased upon cholesterol depletion from platelets.
      Stimulation of cholesterol-depleted platelets with agonists that depend upon
      Galpha(i) activation for full activation displayed significant loss of
      aggregation and secretion, but showed restoration when simultaneously stimulated
      with the Galpha(z)-coupled agonist epinephrine. Finally, Galpha(i) preferentially
      localizes to lipid rafts as determined by sucrose density centrifugation. We
      conclude that Galpha(i) signaling downstream of P2Y12 activation, but not
      Galpha(q) or Galpha(z) signaling downstream of P2Y1 or alpha2A activation,
      respectively, has a requirement for lipid rafts that is necessary for its
      function in ADP-mediated platelet activation.

PMID- 15869602
TI  - The leptin receptor system of human platelets.
AB  - Obesity is associated with elevated levels of leptin in the blood. Elevated
      leptin is a risk factor for thrombosis in humans, and leptin administration
      promotes platelet activation and thrombosis in the mouse. The current study
      examines the effect of leptin on human platelets, and provides initial insights
      into the nature of the leptin receptor on these platelets. Leptin potentiated the
      aggregation of human platelets induced by low concentrations of ADP, collagen and
      epinephrine. However, the response varied significantly between donors, with
      platelets from some donors (approximately 40%) consistently responding to leptin
      (responders) and those from other donors (approximately 60%) never responding
      (non-responders). Western blotting and reverse transcriptase-polymerase chain
      reaction (RT-PCR) experiments showed that platelets from both groups only express
      the signaling form of the leptin receptor, and that responder platelets express
      higher levels of this receptor than non-responders. Ligand-binding assays
      demonstrate specific, saturable binding of leptin to platelets from both groups
      with apparent K(d) values of 76 +/- 20 nM for responders and 158 +/- 46 nM for
      non-responders. Thus, the decreased sensitivity of non-responder platelets to
      leptin does not result from the absence of the signaling form of this receptor,
      but may reflect differences in its level of expression and/or affinity for
      leptin. These preliminary studies demonstrate that platelets are a major source
      of leptin receptor in the circulation, and suggest that leptin-responsive
      individuals may have a higher risk for obesity-associated thrombosis than non
      responsive individuals.

PMID- 15869603
TI  - Selective inducible nitric oxide synthase inhibition attenuates organ dysfunction
      and elevated endothelin levels in LPS-induced DIC model rats.
AB  - We examined the role of nitric oxide (NO) produced by an inducible isoform of NO
      synthase (iNOS) using N[6]-(iminoethyl)-lysine (L-NIL), a selective iNOS
      inhibitor, in the rat model of lipopolysaccharide (LPS)-induced disseminated
      intravascular coagulation (DIC) and investigated changes in organ function,
      plasma levels of NOX (metabolites of NO) and endothelin. We induced experimental
      DIC by the sustained infusion of 30 mg kg(-1) LPS for 4 h via the tail vein. We
      then investigated the effect of L-NIL (6 mg kg(-1), from - 0.5 to 4 h) on LPS
      induced DIC. Blood was withdrawn at 4 and 8 h, and all four groups (LPS with or
      without L-NIL at 4 and 8 h) consisted of eight rats. Three of the animals in the
      8-h LPS group died, and we examined blood samples from five rats in this group.
      None of the other rats died. The LPS-induced elevation of creatinine, alanine
      aminotransferase, glomerular fibrin deposition and plasminogen activator
      inhibitor was significantly suppressed by L-NIL coadministration, although L-NIL
      did not affect the platelet count, fibrinogen concentration or the level of
      thrombin-antithrombin complex. Moreover, plasma levels of the D-dimer that
      reflect the lysis of cross-linked fibrin were significantly increased by L-NIL
      coadministration in the LPS-induced DIC model. Plasma levels of NOX and
      endothelin were obviously increased by LPS infusion. However, both levels were
      significantly suppressed in the LPS + L-NIL group, when compared with the LPS
      group. Although mean arterial pressure (MAP) was significantly decreased between
      2 and 8 h compared with the control in the LPS group, this depression was
      significantly attenuated in the LPS + L-NIL group. Our results suggest that NO
      induced by iNOS contributes to hypotension (depressed MAP), the progression of
      hepatic and renal dysfunction, microthrombus deposition and elevated endothelin
      levels in the rat model of LPS-induced DIC.

PMID- 15869604
TI  - Tissue factor enhances protease-activated receptor-2-mediated factor VIIa cell
      proliferative properties.
AB  - In addition to its hemostatic functions, factor (F)VIIa exhibits cell
      proliferative properties as seen in angiogenesis and tumor growth. A role for
      tissue factor (TF) and protease-activated receptors (PAR)-1 and -2 in cell
      proliferation remain to be clarified. We tested the hypothesis that FVIIa induces
      cell proliferation by a mechanism involving TF and PAR-2. Human recombinant FVIIa
      induced cell proliferation of human BOSC23 cells transfected with plasmid
      containing human TF DNA sequence. Because DNA primase 1 (PRIM1) plays an
      essential role in cell proliferation, we used the cloned PRIM1 promoter upstream
      of the reporter gene chloramphenicol acetyl transferase (CAT) to elucidate the
      mode of action of FVIIa. FVIIa evoked a dose-dependent increase in cell
      proliferation and PRIM1 induction, which were markedly potentiated (4-5-fold) by
      the presence of TF and abrogated by TF antisense oligonucleotide. PRIM1 induction
      by FVIIa was also abolished by PAR-2 but not by PAR-1 antisense. In contrast,
      thrombin induced a small increase in CAT activity which was unaffected by TF, but
      was prevented only by PAR-1 antisense as well as the thrombin inhibitor hirudin.
      Proliferative properties of FVIIa were associated with a TF-dependent increase in
      intracellular calcium and were mediated by a concordant phosphorylation of p44/42
      MAP kinase. In conclusion, data reveal that FVIIa induces PRIM1 and ensuing
      cellular proliferation via a TF- and of the PARs entirely PAR-2-dependent
      pathway, in distinction to that of thrombin which is PAR-1-dependent and TF
      independent. We speculate that FVIIa-TF-PAR-2 inhibitors may be effective in
      suppressing cell proliferation.

PMID- 15869605
TI  - Cloning, expression and functional characterization of the full-length murine
      ADAMTS13.
AB  - Functional deficiency or absence of the human von Willebrand factor (VWF)
      cleaving protease (VWF-cp), recently termed ADAMTS13, has been shown to cause
      acquired and congenital thrombotic thrombocytopenic purpura (TTP), respectively.
      As a first step towards developing a small animal model of TTP, we have cloned
      the complete (non-truncated) murine Adamts13 gene from BALB/c mice liver poly A+
      mRNA. Murine ADAMTS13 is a 1426-amino-acid protein with a high homology and
      similar structural organization to the human ortholog. Transient expression of
      the murine Adamts13 cDNA in HEK 293 cells yielded a protein with a molecular
      weight of approximately 180 kDa which degraded recombinant murine VWF (rVWF) in a
      dose-dependent manner. The cleavage products of murine rVWF had the expected size
      of 140 and 170 kDa. Murine ADAMTS13 was inhibited by EDTA and the plasma from a
      TTP patient.

PMID- 15869606
TI  - Hemostatic abnormalities associated with obesity and the metabolic syndrome.

PMID- 15869613
TI  - Increased plasminogen activator inhibitor-1 levels in android obesity:
      correlation with oxidative stress.

PMID- 15869614
TI  - Temporary relief of symptomatic Von Willebrand disease by multiple myeloma.

PMID- 15869615
TI  - HMR 3339, a novel selective estrogen receptor modulator, reduces concentrations
      of procarboxypeptidase U, an inhibitor of fibrinolysis. A randomized, placebo
      controlled study in postmenopausal women.

PMID- 15869616
TI  - The poor quality of streptokinase products in use in developing countries.

PMID- 15869617
TI  - High prevalence of abnormal preoperative coagulation tests in patients with
      adolescent idiopathic scoliosis.

PMID- 15869618
TI  - Temporary inferior vena caval filter use in pregnancy.

PMID- 15869619
TI  - A monoclonal antibody that inhibits mouse tissue factor function.

PMID- 15869620
TI  - Is contrast venography a valid surrogate outcome measure in venous
      thromboembolism prevention studies?

PMID- 15869621
TI  - The protective effect of the factor XIII Val34Leu mutation on the risk of deep
      venous thrombosis is dependent on the fibrinogen level.

PMID- 15869622
TI  - Ximelagatran and melagatran vs. low-molecular-weight heparin in major orthopedic
      surgery: relationship between efficacy and safety and timing of initial
      administration.

PMID- 15869623
TI  - A further face of the partial thromboplastin time APTT.

PMID- 15869624
TI  - Is citrate deficiency universal?

PMID- 15869625
TI  - Delayed tirofiban-induced thrombocytopenia: two case reports.

PMID- 15869626
TI  - Budd-Chiari syndrome in a paroxysmal nocturnal hemoglobinuria patient with
      coexistence of factor II and MTHFR mutations.

PMID- 15869627
TI  - More on: fluvastatin inhibits up-regulation of tissue factor expression by
      antiphospholipid antibodies on endothelial cells.

PMID- 15869628
TI  - More on: tissue factor in neutrophils.

PMID- 15869629
TI  - More on: a survey of thrombosis prophylaxis use in patients undergoing
      arthroscopic surgery.

PMID- 15869630
TI  - More on: the early discoveries of collagen-platelet interaction and studies on
      its role in hemostatic plug formation.

PMID- 15869632
TI  - Functional-structural plant modelling.

PMID- 15869633
TI  - Fructans and freezing tolerance.

PMID- 15869634
TI  - Leaf-level light compensation points in shade-tolerant woody seedlings.

PMID- 15869635
TI  - Advances in forest tree genomics. Forest Trees Workshop, Plant and Animal Genome
      XIII Conference, San Diego, CA, USA, January 2005.

PMID- 15869636
TI  - Cell walls: the boundaries of plant development. The role of the extracellular
      matrix in the control of plant development: the 13th New Phytologist Symposium,
      London, UK, January 2005.

PMID- 15869637
TI  - Forest fragmentation effects on patch occupancy and population viability of
      herbaceous plant species.
AB  - Habitat fragmentation is one of the major threats to species diversity. In this
      review, we discuss how the genetic and demographic structure of fragmented
      populations of herbaceous forest plant species is affected by increased genetic
      drift and inbreeding, reduced mate availability, altered interactions with
      pollinators, and changed environmental conditions through edge effects. Reported
      changes in population genetic and demographic structure of fragmented plant
      populations have, however, not resulted in large-scale extinction of forest
      plants. The main reason for this is very likely the long-term persistence of
      small and isolated forest plant populations due to prolonged clonal growth and
      long generation times. Consequently, the persistence of small forest plant
      populations in a changing landscape may have resulted in an extinction debt, that
      is, in a distribution of forest plant species reflecting the historical landscape
      configuration rather than the present one. In some cases, fragmentation appears
      to affect ecosystem integrity rather than short-term population viability due to
      the opposition of different fragmentation-induced ecological effects. We finally
      discuss extinction and colonization dynamics of forest plant species at the
      regional scale and suggest that the use of the metapopulation concept, both
      because of its heuristic power and conservation applications, may be fruitful.

PMID- 15869638
TI  - Impacts of parasitic plants on natural communities.
AB  - Parasitic plants have profound effects on the ecosystems in which they occur.
      They are represented by some 4000 species and can be found in most major biomes.
      They acquire some or all of their water, carbon and nutrients via the vascular
      tissue of the host's roots or shoots. Parasitism has major impacts on host
      growth, allometry and reproduction, which lead to changes in competitive balances
      between host and nonhost species and therefore affect community structure,
      vegetation zonation and population dynamics. Impacts on hosts may further affect
      herbivores, pollinators and seed vectors, and the behaviour and diversity of
      these is often closely linked to the presence and abundance of parasitic plants.
      Parasitic plants can therefore be considered as keystone species. Community
      impacts are mediated by the host range of the parasite (the diversity of species
      that can potentially act as hosts) and by their preference and selection of
      particular host species. Parasitic plants can also alter the physical environment
      around them--including soil water and nutrients, atmospheric CO2 and temperature-
      and so may also be considered as ecosystem engineers. Such impacts can have
      further consequences in altering the resource supply to and behaviour of other
      organisms within parasitic plant communities.

PMID- 15869639
TI  - Plant immunophilins: functional versatility beyond protein maturation.
AB  - Originally identified as the cellular targets of immunosuppressant drugs, the
      immunophilins encompass two ubiquitous protein families: the FK-506 binding
      proteins or FKBPs, and the cyclosporin-binding proteins or cyclophilins. Present
      in organisms ranging from bacteria to animals and plants, these proteins are
      characterized by their enzymatic activity; the peptidyl-prolyl cis-trans
      isomerization of polypeptides. Whilst this function is important for protein
      folding, it has formed the functional basis for more complex interactions between
      immunophilins and their target proteins. Beginning with a brief historical
      overview of the immunophilin family, and a representative illustration of the
      current state of knowledge that has accumulated for these proteins in diverse
      organisms, a detailed description is presented of the recent advances in the
      elucidation of the role of this ubiquitous protein family in plant biology.
      Though still in its infancy, investigation into the function of plant
      immunophilins has so far yielded interesting results--as a significant component
      of the chloroplast proteome, the abundance of immunophilins located in the
      thylakoid lumen suggests that these proteins may play important roles in this
      relatively uncharacterized subcellular compartment. Moreover, the importance of
      the complex multidomain immunophilins in functions pertaining to development is
      underscored by the strong phenotypes displayed by their corresponding mutants.

PMID- 15869640
TI  - New understanding on phloem physiology and possible consequences for modelling
      long-distance carbon transport.
AB  - Most current models of assimilate carbohydrate partitioning are based on growth
      patterns observed under a range of experimental conditions, from which a set of
      empirical rules are derived to simulate partitioning. As a result, they are not
      good at extrapolating to other conditions; this requires a mechanistic approach,
      which only transport-resistance (TR) models currently provide. We examine an
      approach to incorporating recent progress in phloem physiology into the TR
      approach, which leads to a 'minimalist' Munch model of a branched system with
      competing sinks. In vivo whole-plant measurements have demonstrated that C-flow
      rates are dependent not only on the properties of the sink, but also on the
      properties of the whole transport system, and the detailed dynamics of this
      behaviour is mimicked by the proposed model. This model provides a sound
      theoretical framework for an unambiguous definition of sink and source strengths,
      with sink priority being an emergent property of the model. Further developments
      are proposed, some of which have already had limited application, to cope with
      the complexity of plants; the emphasis is on a modular approach, together with
      the importance of choosing the appropriate scale level for both structure and
      function. Whole-plant experiments with in vivo measurement of the phloem dynamics
      will be needed to help with this choice.

PMID- 15869641
TI  - Phylloclimate or the climate perceived by individual plant organs: what is it?
      How to model it? What for?
AB  - This review introduces the emergence of a new research topic, phylloclimate,
      located at the crossroads between ecophysiology and canopy microclimate research.
      Phylloclimate corresponds to the physical environment actually perceived by each
      individual aerial organ of a plant population, and is described by physical
      variables such as spectral irradiance, temperature, on-leaf water and features of
      around-organ air (wind speed, temperature, humidity, etc.). Knowing the actual
      climate in which plant organs grow may enable advances in the understanding of
      plant-environment interactions, as knowing surface temperature instead of air
      temperature enabled advances in the study of canopy development. Characterizing
      phylloclimate variables, using experimental work or modeling, raises many
      questions such as the choice of suitable space- and time-scale as well as the
      ability to individualize plant organs within a canopy. This is of particular
      importance when aiming to link phylloclimate and function-structure plant models.
      Finally, recent trends and challenging questions in phylloclimate research are
      discussed, as well as the possible applications of phylloclimate results.

PMID- 15869642
TI  - Crown architecture in sun and shade environments: assessing function and trade
      offs with a three-dimensional simulation model.
AB  - Sun and shade environments place markedly different constraints on the
      photosynthetic performance of plants. Leaf-level photosynthetic responses to sun
      and shade have been extensively investigated, whereas there has been much less
      research on the functional role of crown architecture in these environments. This
      paper focuses on the role of architecture in maximizing light capture and
      photosynthesis in shaded understories and in minimizing exposure to excess
      radiation in open high light environments. Understanding these contrasting roles
      of architecture is facilitated by application of a three-dimensional structural
      functional model, Y-plant. Surveys of understory plants reveal a diversity of
      architectures but a strong convergence at only modest light-capture efficiencies
      because of significant self-shading. Simulations with Psychotria species revealed
      that increasing internode lengths would increase light-capture efficiencies and
      whole plant carbon gain. However, the costs of the additional required
      biomechanical support was high, which, in terms of relative growth rates, would
      override the advantage provided by higher light-capture efficiencies. In high
      light environments, leaf angles and self-shading provide structural
      photoprotection, minimizing potential damage from photoinhbition. Simulations
      reveal that without these structural protections photoinhibition of
      photosynthesis is likely to be much greater with daily carbon gain significantly
      reduced.

PMID- 15869643
TI  - Towards a generic architectural model of tillering in Gramineae, as exemplified
      by spring wheat (Triticum aestivum).
AB  - This paper presents an architectural model of wheat (Triticum aestivum), designed
      to explain effects of light conditions at the individual leaf level on tillering
      kinetics. Various model variables, including blade length and curvature, were
      parameterized for spring wheat, and compared with winter wheat and other
      Gramineae species. The architectural model enables simulation of plant properties
      at the level of individual organs. Parameterization was based on data derived
      from an outdoor experiment with spring wheat cv. Minaret. Final organ dimensions
      of tillers could be modelled using the concept of relative phytomer numbers.
      Various variables in spring wheat showed marked similarities to winter wheat and
      other species, suggesting possibilities for a general Gramineae architectural
      model. Our descriptive model is suitable for our objective: investigating light
      effects on tiller behaviour. However, we plan to replace the descriptive
      modelling solutions by physiological, mechanistic solutions, starting with the
      localized production and partitioning of assimilates as affected by abiotic
      growth factors.

PMID- 15869644
TI  - Analysis of the plant architecture via tree-structured statistical models: the
      hidden Markov tree models.
AB  - Plant architecture is the result of repetitions that occur through growth and
      branching processes. During plant ontogeny, changes in the morphological
      characteristics of plant entities are interpreted as the indirect translation of
      different physiological states of the meristems. Thus connected entities can
      exhibit either similar or very contrasted characteristics. We propose a
      statistical model to reveal and characterize homogeneous zones and transitions
      between zones within tree-structured data: the hidden Markov tree (HMT) model.
      This model leads to a clustering of the entities into classes sharing the same
      'hidden state'. The application of the HMT model to two plant sets (apple trees
      and bush willows), measured at annual shoot scale, highlights ordered states
      defined by different morphological characteristics. The model provides a
      synthetic overview of state locations, pointing out homogeneous zones or
      ruptures. It also illustrates where within branching structures, and when during
      plant ontogeny, morphological changes occur. However, the labelling exhibits some
      patterns that cannot be described by the model parameters. Some of these
      limitations are addressed by two alternative HMT families.

PMID- 15869645
TI  - Performance of trees in forest canopies: explorations with a bottom-up functional
      structural plant growth model.
AB  - Here we present a functional-structural plant model that integrates the growth of
      metamers into a growing, three-dimensional tree structure, and study the effects
      of different constraints and strategies on tree performance in different
      canopies. The tree is a three-dimensional system of connected metamers, and
      growth is defined by the flush probability of metamers. Tree growth was simulated
      for different canopy light environments. The result suggest that: the constraints
      result in an exponential, logistic and decay phase; a mono-layered-leaf crown
      results from self-shading in a closed canopy; a strong apical control results in
      slender trees like tall stature species; the interaction between weak apical
      control and light response results in a crown architecture and performance known
      from short stature species in closed forest; correlated leaf traits explain
      interspecific differences in growth, survival and adult stature. The model
      successfully unravels the interaction effects of different constraints and
      strategies on tree growth in different canopy light environments.

PMID- 15869646
TI  - Using the canonical modelling approach to simplify the simulation of function in
      functional-structural plant models.
AB  - Functional-structural plant models that include detailed mechanistic
      representation of underlying physiological processes can be expensive to
      construct and the resulting models can also be extremely complicated. On the
      other hand, purely empirical models are not able to simulate plant adaptability
      and response to different conditions. In this paper, we present an intermediate
      approach to modelling plant function that can simulate plant response without
      requiring detailed knowledge of underlying physiology. Plant function is modelled
      using a 'canonical' modelling approach, which uses compartment models with flux
      functions of a standard mathematical form, while plant structure is modelled
      using L-systems. Two modelling examples are used to demonstrate that canonical
      modelling can be used in conjunction with L-systems to create functional
      structural plant models where function is represented either in an accurate and
      descriptive way, or in a more mechanistic and explanatory way. We conclude that
      canonical modelling provides a useful, flexible and relatively simple approach to
      modelling plant function at an intermediate level of abstraction.

PMID- 15869647
TI  - Barley morphology, genetics and hormonal regulation of internode elongation
      modelled by a relational growth grammar.
AB  - A multiscaled ecophysiological model of barley (Hordeum vulgare) development is
      presented here. The model is based on the new formalism of relational growth
      grammars (RGG), an extension of L-systems, and implemented using the new
      modelling language XL. It is executable in the interactive modelling platform
      GroIMP. The model consists of a set of morphogenetic rules, combined with a
      metabolic regulatory network, which simulates the biosynthesis of gibberellic
      acid (GA1). GA1 and two of its metabolic precursors are transported along the
      developing simulated structure. Local concentrations of GA1 determine internode
      elongation. Furthermore, virtual barley individuals are chosen interactively from
      a population, based on genotype, and (sexual or asexual) reproduction is
      simulated. Genotype and phenotype of the population are visualized. Seven
      Mendelian genes have been implemented in the model so far; some of these directly
      influence the GA-regulation network. The model exemplifies and validates the new
      formalism and modelling language. RGG have the capability to represent genetic,
      metabolic and morphological aspects of plant development and reproduction, all
      within the same framework.

PMID- 15869648
TI  - Using L-systems for modeling source-sink interactions, architecture and
      physiology of growing trees: the L-PEACH model.
AB  - Functional-structural plant models simulate the development of plant structure,
      taking into account plant physiology and environmental factors. The L-PEACH model
      is based on the development of peach trees. It demonstrates the usefulness of L
      systems in constructing functional-structural models. L-PEACH uses L-systems both
      to simulate the development of tree structure and to solve differential equations
      for carbohydrate flow and allocation. New L-system-based algorithms are devised
      for simulating the behavior of dynamically changing structures made of hundreds
      of interacting, time-varying, nonlinear components. L-PEACH incorporates a carbon
      allocation model driven by source-sink interactions between tree components.
      Storage and mobilization of carbohydrates during the annual life cycle of a tree
      are taken into account. Carbohydrate production in the leaves is simulated based
      on the availability of water and light. Apices, internodes, leaves and fruit grow
      according to the resulting local carbohydrate supply. L-PEACH outputs an animated
      three-dimensional visual representation of the growing tree and user-specified
      statistics that characterize selected stages of plant development. The model is
      applied to simulate a tree's response to fruit thinning and changes in water
      stress. L-PEACH may be used to assist in horticultural decision-making processes
      after being calibrated to specific trees.

PMID- 15869649
TI  - A functional-structural model of elongation of the grass leaf and its
      relationships with the phyllochron.
AB  - The emergence of a regular phyllochron from the dynamic processes of leaf
      initiation, leaf elongation and whorl construction suggests causal relationships
      between leaf elongation and leaf emergence. This paper presents a hypothesis as
      to how the ontogeny of the growth zone of leaves is triggered by emergence
      events, and implements it in a dynamic model of leaf elongation. Two different
      experiments, presenting two contrasted cases of relationships between leaf
      emergence and kinetics of leaf elongation, were analysed and interpreted with the
      model in terms of the functioning of the growth zone. Analysis of elongation
      kinetics revealed that the hypothesis allows for several contrasted elongation
      patterns that were observed, and for a regular phyllochron emerging from the
      variable dynamic of elongation. The model was able to simulate these patterns,
      and helped to identify the mechanisms underlying the key points of the analysis.
      The hypothesis is not demonstrated, but its coherence and robustness are
      established, which should inform a renewal of the modelling of leaf elongation in
      architectural models.

PMID- 15869650
TI  - Jasmonates and Na-orthovanadate promote resveratrol production in Vitis vinifera
      cv. Barbera cell cultures.
AB  - Here the effect of jasmonic acid, methyljasmonate and Na-orthovanadate on the
      production of resveratrol was studied in Vitis vinifera cv. Barbera cell
      suspension cultures. Na-orthovanadate at 0.1 mm and 1 mm concentration was
      efficient in promoting the production and/or accumulation and release in the
      culture medium of cis-resveratrol while trans-resveratrol levels were not
      affected by this treatment. Methyljasmonate was highly effective in stimulating
      both trans- and cis-resveratrol endogenous accumulation, as well as their release
      into the culture medium. Cis-resveratrol was absent or detected in very low
      amounts in the controls. Jasmonic acid was less efficient than methyljasmonate in
      promoting endogenous resveratrol accumulation, but it stimulated the release in
      the culture medium especially of cis-resveratrol. Gel analysis was performed on
      control and 10 microm MeJA treated cell suspensions. Results showed an up
      regulation of the stilbene synthase demonstrating that MeJA stimulated the
      synthesis ex-novo of this protein.

PMID- 15869651
TI  - Three loblolly pine CesA genes expressed in developing xylem are orthologous to
      secondary cell wall CesA genes of angiosperms.
AB  - Specific plant cellulose synthases (CesA), encoded by a multigene family, are
      necessary for secondary wall synthesis in vascular tissues and are critical to
      wood production. We obtained full-length clones for the three CesAs that are
      highly expressed in developing xylem and examined their phylogenetic
      relationships and expression patterns in loblolly pine tissues. Full-length CesA
      clones were isolated from cDNA of developing loblolly pine (Pinus taeda) xylem
      and phylogenetic inferences made from plant CesA protein sequences. Expression of
      the three genes was examined by Northern blot analysis and semiquantitative RT
      PCR. Each of three PtCesA genes is orthologous to one of the three angiosperm
      secondary cell wall CesAs. The PtCesAs are coexpressed in tissues of loblolly
      pine with tissues undergoing secondary cell wall biosynthesis showing the highest
      levels of expression. Phylogenetic and expression analyses suggest that
      functional roles for these loblolly pine CesAs are analogous to those of
      orthologs in angiosperm taxa. Based upon evidence from this and other studies, we
      suggest division of seed plant CesA genes into six major paralogous groups, each
      containing orthologs from various taxa. Available evidence suggests that
      paralogous CesA genes and their distinct functional roles evolved before the
      divergence of gymnosperm and angiosperm lineages.

PMID- 15869652
TI  - Cloning, characterization and functional analysis of novel 6-kestose
      exohydrolases (6-KEHs) from wheat (Triticum aestivum).
AB  - Cereals accumulate graminan-type fructans which are subject to stress-related
      degradation by fructan 1-exohydrolases (1-FEHs) and fructan 6-exohydrolases (6
      FEHs). To find new FEH genes related to freezing tolerance, a cold-hardened wheat
      crown cDNA library was screened. Here we report the cloning, purification and
      characterization of two novel 6-kestosidase (6-KEH) isoenzymes from wheat crowns
      (Triticum aestivum). Functional characterization in Pichia pastoris confirmed the
      extreme substrate selectivity for the fructan trisaccharide 6-kestose. Northern
      blotting showed that 6-KEH transcripts were constantly detected at the same level
      from autumn to winter in crown but not in leaf tissues. Apoplastic fluid
      isolations and activity measurements strongly suggest that 6-KEH is localized in
      the apoplast. It is proposed that 6-KEHs, together with other FEHs, might be
      involved in the breakdown of apoplastic fructans which may fulfil a role as
      membrane protectors under stress. Alternatively, a role in signalling processes,
      or in the degradation of exogenous 6-kestose from bacterial origin, cannot be
      excluded.

PMID- 15869653
TI  - Supply pre-emption, not concentration reduction, is the mechanism of competition
      for nutrients.
AB  - Concentration reduction theory is the leading theory regarding the mechanism of
      competition for nutrients in soils among plants, yet it has not been rigorously
      tested. Here we used a spatially explicit, fine-scale grid-based model that
      simulated diffusion and plant uptake of nutrients by plants in soil to test
      whether concentration reduction theory was appropriate for terrestrial plant
      competition for nutrients. In the absence of competition, increasing the rate of
      diffusion allows a plant to maintain positive growth rates below the lowest
      average concentration to which it can reduce nutrients in soil solution (R*). As
      such, differences among plants in the reduction of soil moisture, which here
      primarily affects nutrient diffusion, can cause R* to predict competitive success
      incorrectly. The stronger competitor for nutrients captures the largest
      proportion of the nutrient supply by ensuring nutrients contact its roots before
      those of a competitor. Although the metric derived from concentration reduction
      theory, R*, might have predictive power for competitive outcomes in terrestrial
      ecosystems, this evidence suggests that plants outcompete other plants for
      nutrients by pre-empting the supply, not reducing the average concentration.

PMID- 15869654
TI  - Ozone foliar symptoms in woody plant species assessed with ultrastructural and
      fluorescence analysis.
AB  - This paper compares the responses to ozone in five woody species: Fagus sylvatica
      (FS), Acer pseudoplatanus (AP), Fraxinus excelsior (FE), Viburnum lantana (VL)
      and Ailanthus altissima (AA). The hypothesis being tested was that the strategies
      that plants adopt to resist oxidative pressure are species-specific. The study
      was carried out on field grown plants in an area in Northern Italy characterized
      by elevated levels of ozone pollution. The observations were made both at
      ultrastructural (using light and electronic microscopy) and physiological (using
      chlorophyll a transient fluorescence and microspectral fluorometry) level. Common
      responses were: the hypersensitive response (i.e. the death of palisade mesophyll
      cells) and the formation of callose layers separating injured from healthy cells.
      FS and AP were capable of thickening the palisade mesophyll cell walls. This
      thickening process involved changes in cell wall chemical structure, evidenced by
      the accumulation of yellow autofluorescence compounds. Species-specific
      behaviours were observed with the fluorescence analysis, with special reference
      to the photochemical de-excitation constant (Kp). This value increased in FE and
      AP, and decreased in AA. The observed responses are interpreted as adaptative
      strategies against the ozone stress. The increase of Kp indicates that the
      reaction centres were working as more effective quenchers.

PMID- 15869655
TI  - Is UV-B radiation affecting charophycean algae in shallow freshwater systems?
AB  - The objective of this study was to determine the effects of UV-B radiation on
      charophycean algae under natural conditions, since charophytes enhance water
      transparency in freshwater systems and levels of UV-B radiation have increased by
      ozone depletion. Potential and actual UV-B effects were studied by combining a
      glasshouse experiment in which plants were exposed to various levels of UV-B
      radiation and field measurements in two freshwater systems dominated by
      charophytes in the Netherlands. The glasshouse experiment showed that charophytes
      were sensitive to UV-B radiation. UV-B radiation negatively affected growth,
      while it increased levels of DNA damage in Chara aspera. Moreover, the
      charophytes did not seem to develop UV-B screens to protect against UV-B
      radiation since no increase in UV-B absorbing compounds was found. At field
      conditions, both spectroradiometrical measurements and DNA dosimeters showed that
      UV-B radiation was attenuated quickly in both freshwater systems, indicating that
      UV-B does not reach the submerged charophyte vegetation. However, specific
      conditions, like fluctuating water tables, may result in UV-B exposure to
      charophytes for certain periods annually.

PMID- 15869656
TI  - Conventional detection methodology is limiting our ability to understand the
      roles and functions of fine roots.
AB  - We lack a thorough conceptual and functional understanding of fine roots. Studies
      that have focused on estimating the quantity of fine roots provide evidence that
      they dominate overall plant root length. We need a standard procedure to quantify
      root length/biomass that takes proper account of fine roots. Here we investigated
      the extent to which root length/biomass may be underestimated using conventional
      methodology, and examined the technical reasons that could explain such
      underestimation. Our discussion is based on original X-ray-based measurements and
      on a literature review spanning more than six decades. We present evidence that
      root-length recovery depends strongly on the observation scale/spatial resolution
      at which measurements are carried out; and that observation scales/resolutions
      adequate for fine root detection have an adverse impact on the processing times
      required to obtain precise estimates. We conclude that fine roots are the major
      component of root systems of most (if not all) annual and perennial plants. Hence
      plant root systems could be much longer, and probably include more biomass, than
      is widely accepted.

PMID- 15869657
TI  - Nitrogen supply affects arbuscular mycorrhizal colonization of Artemisia vulgaris
      in a phosphate-polluted field site.
AB  - Root colonization by arbuscular mycorrhizal fungi (AMF) was investigated in
      industrially polluted grassland characterized by exceptionally high phosphorus
      levels (up to 120 g kg(-1) soil). Along a pollution-induced nitrogen gradient,
      soil and tissue element concentrations of Artemisia vulgaris plants and their
      mycorrhizal status were determined. Additionally, we compared mycorrhization
      rates and above-ground biomass of A. vulgaris at N-fertilized and control plots
      in the N-poor area. Despite high soil and tissue P concentrations, plants from N
      deficient plots, which were characterized by low tissue N concentrations and N :
      P ratios, were strongly colonized by AMF, whereas at a plot with comparable P
      levels, but higher soil and plant N concentrations and N : P ratios,
      mycorrhization rates were significantly lower. Correlation analyses revealed a
      negative relationship between percentage root colonization of A. vulgaris by AMF
      and both tissue N concentration and N : P ratio. Accordingly, in the
      fertilization experiment, control plants had higher mycorrhization rates than N
      fertilized plants, whereas the species attained higher biomass at N-fertilized
      plots. The results suggest that N deficiency stimulates root colonization by AMF
      in this extraordinarily P-rich field site.

PMID- 15869658
TI  - Does proximity to mature trees influence ectomycorrhizal fungus communities of
      Douglas-fir seedlings?
AB  - The influence of mature trees on colonization of Douglas-fir (Pseudotsuga
      menziesii) seedlings by ectomycorrhizal fungi (EMF) is not well understood. Here,
      the EMF communities of seedlings planted near and far from trees are compared
      with each other, with EMF of seedlings potted in field soils and with EMF of
      mature trees. Seedlings were planted within 6 m, or beyond 16 m, from residual
      Douglas-fir trees in recently harvested green-tree retention units in Washington
      State, USA, or potted in soils gathered from near each residual tree. Mature tree
      roots were sampled by partly excavating the root system. The EMF communities were
      assessed by polymerase chain reaction-restriction fragment length polymorphism
      and sequence analysis of ribosomal RNA genes. Seedlings near trees had higher
      species richness and diversity of EMF communities compared with seedlings far
      from trees. The EMF communities of seedlings near trees were more similar to
      those of mature trees, while seedlings far from trees were more similar to
      glasshouse seedlings. By enhancing the EMF diversity of seedlings, residual trees
      may maintain or accelerate the re-establishment of mycorrhizal communities
      associated with mature forests.

PMID- 15869659
TI  - Diversity and specificity of ectomycorrhizal fungi retrieved from an old-growth
      Mediterranean forest dominated by Quercus ilex.
AB  - We analysed the ectomycorrhizal (ECM) fungal diversity in a Mediterranean old
      growth Quercus ilex forest stand from Corsica (France), where Arbutus unedo was
      the only other ECM host. On a 6400 m2 stand, we investigated whether oak age and
      host species shaped below-ground ECM diversity. Ectomycorrhizas were collected
      under Q. ilex individuals of various ages (1 yr seedlings; 3-10 yr saplings; old
      trees) and A. unedo. They were typed by ITS-RFLP analysis and identified by match
      to RFLP patterns of fruitbodies, or by sequencing. A diversity of 140 taxa was
      found among 558 ectomycorrhizas, with many rare taxa. Cenococcum geophilum
      dominated (35% of ECMs), as well as Russulaceae, Cortinariaceae and
      Thelephoraceae. Fungal species richness was comparable above and below ground,
      but the two levels exhibited < 20% overlap in fungal species composition. Quercus
      ilex age did not strongly shape ECM diversity. The two ECM hosts, A. unedo and Q.
      ilex, tended to share few ECM species (< 15% of the ECM diversity). Implications
      for oak forest dynamics are discussed.

PMID- 15869660
TI  - Seasonal changes in wood formation of Ulmus pumila and U. minor and its relation
      with Dutch elm disease.
AB  - Elms containing narrow and scattered vessels have been reported to be more
      resistant to Ophiostoma novo-ulmi (Dutch elm disease pathogen) than elms with
      large and contiguous vessels. However, recent measurements in Ulmus pumila and U.
      minor showed a contrary trend. The pin method was applied to 4-yr-old branches of
      eight clones planted in Madrid. During 2002, radial growth increments and vessel
      diameters were measured monthly, and beetle trapping was undertaken weekly. U.
      minor formed larger vessels at the beginning of the season, coinciding with a
      peak of captured beetles, but, up to June 15, vessels were larger for U. pumila.
      The number of vessels per group, the transversal area per vessel group, and the
      mean theoretical hydraulic conductances were significantly higher for U. minor on
      most dates. Researchers should take into consideration the seasonal changes in
      vessel size. The results highlight that seasonal variation of vessel diameters
      and hydraulic parameters, in combination with beetle abundance, are the main
      factors that could explain the different susceptibility of both elm species to O.
      novo-ulmi.

PMID- 15869661
TI  - The Vh8 locus of a new gene-for-gene interaction between Venturia inaequalis and
      the wild apple Malus sieversii is closely linked to the Vh2 locus in Malus pumila
      R12740-7A.
AB  - The wild apple (Malus sieversii) is a large-fruited species from Central Asia,
      which is used as a source of scab resistance in cultivar breeding.
      Phytopathological tests with races of Venturia inaequalis were performed to
      differentiate scab-resistance genes in Malus as well as an avirulence gene in the
      pathogen. A novel gene-for-gene interaction between V. inaequalis and Malus was
      identified. The locus of the scab-resistance gene Vh8 is linked with, or possibly
      allelic to, that of the Vh2 gene in Malus pumila Russian apple R12740-7A, at the
      lower end of linkage group 2 of Malus. Race 8 isolate NZ188B.2 is compatible with
      Vh8, suggesting the loss or modification of the complementary AvrVh8 gene, while
      isolate 1639 overcomes both Vh2 and Vh8, but is incompatible with at least one
      other gene not detected by any of the other race isolates tested. Our research is
      the first to differentiate scab-resistance genes in a putative gene cluster in
      apple with the aid of races of V. inaequalis.

PMID- 15869662
TI  - The origin of a novel form of Senecio (Asteraceae) restricted to sand dunes in
      southern Sicily.
AB  - The taxonomy of diploid Mediterranean Senecio sect. Senecio (Asteraceae) is
      complex, owing to a recent species radiation, high morphological plasticity and
      occasional interspecific hybridization. A study was conducted to resolve the
      origin of a novel form of Senecio restricted to sand dunes in southern Sicily,
      Italy. This has been described previously as morphologically intermediate to
      Senecio gallicus and Senecio glaucus ssp. coronopifolius, indicating a possible
      hybrid origin, or as a variant of Senecio leucanthemifolius. Plants of this form
      grown in a glasshouse were morphologically intermediate to S. glaucus and S.
      leucanthemifolius, but were also similar to some cultivated individuals of S.
      gallicus. No evidence for a hybrid origin was obtained from a survey of random
      amplified polymorphic DNA variation; instead the plants surveyed were most
      closely allied to Tunisian S. glaucus. They were also polymorphic for the same
      set of cpDNA haplotypes present in Tunisian S. glaucus. We conclude that the
      Sicilian Senecio is a variant form of North African S. glaucus ssp.
      coronopifolius, which most probably dispersed to sand dunes in southern Sicily in
      the relatively recent past. The presence of several cpDNA haplotypes in this
      material indicates that there have been multiple introductions of the species to
      Sicily.

PMID- 15869663
TI  - UNITE: a database providing web-based methods for the molecular identification of
      ectomycorrhizal fungi.
AB  - Identification of ectomycorrhizal (ECM) fungi is often achieved through
      comparisons of ribosomal DNA internal transcribed spacer (ITS) sequences with
      accessioned sequences deposited in public databases. A major problem encountered
      is that annotation of the sequences in these databases is not always complete or
      trustworthy. In order to overcome this deficiency, we report on UNITE, an open
      access database. UNITE comprises well annotated fungal ITS sequences from well
      defined herbarium specimens that include full herbarium reference identification
      data, collector/source and ecological data. At present UNITE contains 758 ITS
      sequences from 455 species and 67 genera of ECM fungi. UNITE can be searched by
      taxon name, via sequence similarity using blastn, and via phylogenetic sequence
      identification using galaxie. Following implementation, galaxie performs a
      phylogenetic analysis of the query sequence after alignment either to pre
      existing generic alignments, or to matches retrieved from a blast search on the
      UNITE data. It should be noted that the current version of UNITE is dedicated to
      the reliable identification of ECM fungi. The UNITE database is accessible
      through the URL http://unite.zbi.ee

PMID- 15869664
TI  - Pacemaker-induced mitral regurgitation.

PMID- 15869665
TI  - Prevalence of venous obstruction in permanent endovenous pacing in newborns and
      infants: follow-up study.
AB  - OBJECTIVE: We examined the prevalence of venous obstruction in 12 newborns and
      infants with permanent endovenous ventricular pacing, clinically, and by
      ultrasonographic assessment of hemodynamics (spontaneity, phasicity, velocity,
      and turbulence of flow) and morphologic parameters (compressibility, wall
      thickness, and thrombus presence). MATERIAL AND METHODS: All implantations of
      single ventricular unipolar endovenous steroid leads, were performed via cephalic
      vein, and pacemakers were placed in subcutaneous pocket in right prepectoral
      region. After the vascular surgeon has carefully examined all children for
      presence of venous collaterals in the chest wall, morphologic and hemodynamic
      parameters of the subclavian, axillary, and internal jugular veins, were assessed
      by linear-array color Doppler. Lead capacity (LC) was calculated for each
      patient. RESULTS: Mean age of patients at implant was 6.2 months (range 1 day-12
      months), mean weight 6.5 kg (range 2.25-10 kg), and mean height 60.9 cm (range 48
      78 cm). Mean LC was 1.99 (range 1.14-3.07). Total follow-up was 1023 and mean
      follow-up 85.2 pacing months (range 3-156). No clinical signs of venous
      obstruction were observed. Mild stenosis (20%) of subclavian vein was found by
      color Doppler in 2/12 patients. Both had adequate lead diameter for body surface.
      CONCLUSION: Permanent endovenous pacing is a feasible procedure, even in children
      of body weight less than 10 kg, with quite acceptable impact on venous system
      patency.

PMID- 15869666
TI  - Predictive value of early atrial tachyarrhythmias recurrence after
      circumferential anatomical pulmonary vein ablation.
AB  - OBJECTIVE: Radiofrequency (RF) ablation at the ostia of the pulmonary veins (PVs)
      to cure atrial fibrillation (AF) is often followed by early AF recurrence. The
      aims of this study were to determine the rate of early atrial tachyarrhythmia as
      recurrence after circumferential anatomical PV ablation; to evaluate whether the
      early recurrence of atrial tachyarrhythmias correlates with the long-term outcome
      of ablation; and to identify the predictors of early atrial tachyarrhythmias
      relapse. METHODS: We studied 143 consecutive patients who underwent
      circumferential anatomical PV ablation. We defined early atrial tachyarrhythmias
      relapse as the recurrence of atrial tachyarrhythmias during the first 3 months
      after RF ablation. RESULTS: After a mean follow-up of 18.7 +/- 7.2 months,
      102/143 patients (71%) were deemed responders to ablation. Atrial
      tachyarrhythmias relapsed during the first 3 months of follow-up in 65/143 (46%)
      patients. Patients without early atrial tachyarrhythmias relapse had a higher
      probability of long-term clinical success than patients with early atrial
      tachyarrhythmias relapse (95% vs 43%, P < 0.0001). However, patients who relapsed
      within the first month had 45.5% probability of long-term clinical success. On
      multivariate analysis, the presence of structural heart disease and the lack of a
      successful anatomical ablation of all targeted PV were significantly and
      independently correlated with early atrial tachyarrhythmias relapse. CONCLUSION:
      A delayed cure may be expected in almost 50% of patients in whom atrial
      tachyarrhythmias relapses within the first month after circumferential anatomical
      PV ablation. The presence of structural heart disease and the lack of a
      successful anatomical ablation of all targeted PV predict early atrial
      tachyarrhythmias recurrence.

PMID- 15869667
TI  - Variable electrocardiographic effects of short-term quinidine sulfate
      administration in Brugada syndrome.
AB  - Quinidine, a class I antiarrhythmic agent with blocking property of transient
      outward current, is a possible candidate for the suppression of ventricular
      fibrillation in patients with Brugada syndrome; although there is a concern that
      its ability to these effects may be proarrhythmic. Therefore, we evaluated the
      effect of quinidine sulfate on ST-segment elevation in Brugada syndrome. In 8
      patients with Brugada syndrome, the magnitude of ST-elevation at the J-point
      (ST(J)), and the ST-segment configuration in leads V1-V3, were compared before
      and on day 2 after the initiation of quinidine administration. In 3 patients,
      quinidine attenuated ST(J) by > or = 0.1 mV. Of these 3 patients, ST-segment
      elevation was normalized in 2 patients, while the ST-segment configuration was
      unchanged in another. In another 3 patients, quinidine augmented ST(J) by > or =
      0.1 mV without any change of ST-segment configuration, and the augmentation was
      returned to baseline after the discontinuation of quinidine. Quinidine exhibited
      no effect on the ST-segment in the remaining 2 patients. The favorable effects of
      quinidine on the ST-segment tended to be more pronounced in patients with
      prominent ST-elevation at baseline. In 1 patient, quinidine was effective in
      eliminating both ST-segment elevation and repetitive tachyarrhythmia episodes. In
      conclusion, the effects of quinidine on ST-segment elevation were variable.
      Quinidine may potentially augment the ST-segment elevation in some patients with
      Brugada syndrome.

PMID- 15869668
TI  - Optimal maximum tracking rate of dual-chamber pacemakers required by children and
      young adults for a maximal cardiorespiratory performance.
AB  - INTRODUCTION: Children and young adults require a higher maximum tracking rate
      (MTR) for physical activity. The objective of the present study was to observe
      whether higher MTR of 170 or 190 beats per minute (bpm) have a positive impact on
      the maximal cardiorespiratory capacity of children and young adults in comparison
      with a lower MTR of 140 bpm. METHODS: Fifteen patients with atrioventricular
      block and normal sinus-node chronotropic function (age 7-24 years) with DDD- (14)
      or VDD-pacemakers (PM) (1) were enrolled. First, the MTR was adjusted to 140 bpm
      for 6 weeks and elevated in a second step to 170 or 190 bpm. At the end of each
      period two cardiopulmonary exercise tests, a 24-hour ECG and a PM test were
      performed. RESULTS: All patients increased their maximal heart rate (139.0 +/-
      1.0 vs 177.0 +/- 10.0 bpm, P < 0.001), peak cardiorespiratory capacity (2.4 +/-
      0.6 vs 2.8 +/- 0.7 W/kg, P < 0.001), peak oxygen uptake (28.3 +/- 7.0 vs 35.7 +/-
      9.5 mL/kg/min, P < 0.005), and oxygen uptake (23.7 +/- 7.4 vs 29.3 +/- 8.4
      mL/kg/min, P < 0.02) at the anaerobic threshold. There were no evident heart
      rhythm disturbances with elevated MTR. Patients with a Wenckebach behavior of the
      PM had an attenuated increase of maximal cardiorespiratory performance.
      CONCLUSION: Children and young adults with DDD-/VDD-PM benefit from an elevated
      MTR by an increased cardiorespiratory capacity, without having more heart rhythm
      disturbances. A Wenckebach behavior of the PM should be avoided.

PMID- 15869669
TI  - Optimal side of implant for single-lead VDD pacing: right-sided versus left-sided
      implantation.
AB  - BACKGROUND: Atrial undersensing occurs in a considerable number of patients with
      single-lead VDD pacing. This study tried to determine the role of implant side in
      maintenance of the VDD mode in patients with isolated atrioventricular (AV)
      block. METHODS: Eighty-two patients with isolated AV block (46 females; mean age,
      58 +/- 17 years) received a single-lead VDD pacemaker (Medtronic Kappa, n = 70
      and St. Jude Medical Affinity, n = 12). The patients were randomly assigned to
      one of two implantation groups (group I: right-sided VDD and group II: left-sided
      VDD). In each group, the P-wave amplitudes were determined at implantation,
      predischarge, 2-month, and 6-month follow-up. At each follow-up visit, stored
      event histograms of pacemaker were also retrieved. The atrial sensing
      measurements were compared between two groups. RESULTS: Implantation was easier
      from right side (1.7 +/- 1.0 vs 2.8 +/- 1.7 attempts, P = 0.001). Implant P-wave
      was higher in group I compared to group II (4.2 +/- 1.7 vs 2.7 +/- 1.0 mV, P <
      0.0001). During follow-up, higher P-wave amplitudes were obtained in group I both
      at predischarge (2.6 +/- 1.3 vs 1.4 +/- 1.1 mV, P < 0.0001), 2-month (2.8 +/- 1.8
      vs 1.3 +/- 1.0 mV, P < 0.0001), and 6-month (2.9 +/- 1.7 vs 1.3 +/- 0.9 mV, P <
      0.0001) evaluations but remained stable throughout the 6 months in both groups.
      After implantation, VDD function was better maintained in group I than group II
      (100% vs 90%, P = 0.026). Incidence of atrial undersensing was lower in group I
      than group II (P = 0.026) in last follow-up visit. CONCLUSIONS: Implant side has
      a significant influence on atrial sensing performance in single-lead VDD pacing.
      Thus, right-side implantation should be the preferred approach for the
      implantation of VDD single-lead systems.

PMID- 15869670
TI  - Effect of IKr blocker nifekalant on atrial action potential duration after
      successful internal cardioversion of chronic atrial fibrillation.
AB  - BACKGROUND: Chronic atrial fibrillation (AF) is characterized by a marked
      decrease in the atrial effective refractory period (ERP) and in the ERP
      adaptation to rate as well as a decrease in the atrial conduction velocity.
      Little information is available about the ionic mechanisms underlying AF in
      humans. MATERIALS AND METHODS: We studied the effect of IKr blocker nifekalant on
      the rate-dependent changes in atrial action potential duration in 11 patients
      after successful internal cardioversion of chronic AF of >2 months duration and
      in 7 patients without AF. In AF patients, right atrial (RA) monophasic action
      potential (MAP) was recorded at pacing cycle lengths (CLs) of 800-250 ms before
      and after administration of nifekalant. In control patients, RAMAP was recorded
      at CLs of 600 and 350 ms before and after administration of nifekalant. RESULTS:
      Nifekalant significantly increased RAMAPD at 90% repolarization (RAMAPD90) at CLs
      of 800-300 ms in the AF patients. The increase in RAMAPD90 by nifekalant became
      significantly smaller at shorter CLs (42.5 +/- 12.4 ms at a CL of 600 ms vs 32.8
      +/- 14.5 ms at a CL of 350 ms, P < 0.05). Effect of nifekalant on RAPMAPD was
      attenuated at CL of 600 ms in AF patients in comparison to control patients
      (increase in RAMAPD in control; 73.0 +/- 36.6 ms vs increase in RAMAPD in AF;
      42.5 +/- 12.4 ms, P < 0.05); however, it was similar at a CL of 350 ms between
      control and AF patients. CONCLUSIONS: Electrophysiological effects of nifekalant
      are significantly attenuated in the chronically remodeled human atrium at slower
      heart rates, but the beneficial effect of RAMAPD prolongation by IKr blocker was
      well-preserved even at shorter CLs after chronic AF.

PMID- 15869671
TI  - New simplified technique for 3D mapping and ablation of right ventricular outflow
      tract tachycardia.
AB  - OBJECTIVE: To evaluate the safety and efficacy of using a circular multielectrode
      catheter for mapping and ablation of ventricular tachycardia (VT) or premature
      ventricular complexes (PVCs) from the right ventricular outflow tract (RVOT).
      BACKGROUND: Three-dimensional (3D) mapping systems are commonly used for mapping
      and ablation of RVOT VT and PVCs. Newer catheters that are circular with multiple
      electrodes, such as the Lasso catheter, are capable of simultaneously recording
      from multiple points within a circumferential plane. Given the tubular structure
      of the RVOT, these catheters could be used for mapping tachycardias from the
      RVOT. METHODS: A retrospective cohort study of patients undergoing radiofrequency
      (RF) ablation of RVOT VT or PVCs was performed. In group 1 (n = 7), mapping was
      performed with a single ablation catheter and fluoroscopy. In group 2 (n = 10),
      3D mapping using ESI (n = 9) or CARTO (n = 1) was performed. In group 3 (n = 12),
      mapping was performed with a circular multielectrode catheter (n = 12). All
      ablations were performed with 4-mm tip catheters using RF energy. RESULTS:
      Catheter ablation for RVOT VT (n = 15) or PVCs (n = 14) was performed on 29 cases
      in 26 patients, 9 males. Mean age was 35.9 years. In groups 1, 2, and 3, the mean
      number of lesions was 17.7 +/- 7.7, 13.6 +/- 7.7, and 18.2 +/- 22.7 and the
      median number of lesions was 20, 13, and 5, respectively. There were no
      significant differences in the number of lesions, RF time, fluoroscopy time,
      procedure time, and acute success rate among the three techniques. There were
      three complications in group 2 and one in group 3. CONCLUSION: The use of a
      circular multielectrode catheter is as effective as the other standard available
      3D mapping techniques, both in terms of procedural success and procedural
      characteristics. Additionally, because of the lower cost associated with using
      the circular multielectrode catheter approach, further evaluation should be
      performed to determine whether this is the most cost-effective approach to 3D
      mapping and ablation of RVOT tachycardias.

PMID- 15869672
TI  - Feasibility of using an implantable system to measure thoracic congestion in an
      ambulatory chronic heart failure canine model.
AB  - BACKGROUND: Noninvasive measures of impedance reflect alterations in thoracic
      fluid and pulmonary edema in acute animal and human studies. MATERIALS AND
      METHODS: We evaluated the feasibility of using an implantable impedance measuring
      device and cardiac lead system to monitor intrathoracic congestion in a pacing
      induced heart failure canine model. Three devices were implanted in each of five
      dogs: a modified pacemaker to measure impedance from a defibrillation lead
      implanted in the right ventricle; an implantable hemodynamic monitoring device to
      measure left ventricular end diastolic pressure (LVEDP) and a second pacemaker to
      deliver rapid (240 pulses per minute) ventricular pacing to induce heart failure.
      RESULTS: All five dogs developed severe heart failure after 3-4 weeks of rapid
      pacing and recovered following pacing termination. The LVEDP increased and
      impedance decreased during pacing-induced heart failure and recovered after
      pacing cessation. At the end of pacing, there was a mean impedance reduction of
      10.6 +/- 8.3% and a mean LVEDP increase of 18.1 +/- 4.5 mmHg compared to
      baseline. The impedance and LVEDP were inversely correlated (r =-0.41 to -0.85,
      all P < 0.05). CONCLUSIONS: In the canine model, measurement of chronic
      intrathoracic impedance with an implantable system effectively revealed changes
      in thoracic congestion due to heart failure reflected by LVEDP. These data
      suggest that implantable device-based impedance measurement merits further
      investigation as a tool to monitor the fluid status of heart failure patients.

PMID- 15869673
TI  - Mechanism of atrial flutter occurring late after orthotopic heart transplantation
      with atrio-atrial anastomosis.
AB  - OBJECTIVE: We sought to better define the electrophysiologic mechanism of atrial
      flutter in patients after heart transplantation. BACKGROUND: Atrial flutter is a
      recognized problem in the post-cardiac transplant population. The
      electrophysiologic basis of atrial flutter in this patient population is not
      completely understood. METHODS: Six patients with cardiac allografts and symptoms
      related to recurrent atrial flutter underwent diagnostic electrophysiologic study
      with electroanatomic mapping and radiofrequency catheter ablation. Comparison was
      made with a control non-transplant population of 11 patients with typical
      counterclockwise right atrial flutter. RESULTS: In each case, mapping showed
      typical counterclockwise activation of the donor-derived portion of the right
      atrium, with concealed entrainment shown upon pacing in the cavotricuspid isthmus
      (CTI). The anastomotic suture line of the atrio-atrial anastomosis formed the
      posterior barrier of the reentrant circuit. Ablation of the electrically active,
      donor-derived portion of the CTI was sufficient to terminate atrial flutter and
      render it noninducible. Comparison with the control population showed that the
      electrically active portion of the CTI was significantly shorter in patients with
      transplant-associated flutter and that ablation was accomplished with the same or
      fewer radiofrequency lesions. CONCLUSIONS: Atrial flutter in cardiac transplant
      recipients is a form of typical counterclockwise, isthmus-dependent flutter in
      which the atrio-atrial anastomotic suture line forms the posterior barrier of the
      reentrant circuit. Ablation in the donor-derived portion of the CTI is sufficient
      to create bidirectional conduction block and eliminate this arrhythmia. Ablation
      or surgical division of the donor CTI at the time of transplantation could
      prevent this arrhythmia.

PMID- 15869674
TI  - Successful pulmonary vein isolation using transvenous catheter cryoablation
      improves quality-of-life in patients with atrial fibrillation.
AB  - BACKGROUND: Recent studies have demonstrated that transvenous catheter
      cryoablation is a safe and effective technique for creating pulmonary veins (PVs)
      electrical isolation for the treatment of atrial fibrillation (AF). However, the
      impacts of this procedure on quality-of-life (QoL) have not been evaluated.
      METHODS AND RESULTS: We studied the effects of PV isolation using transvenous
      catheter cryoablation on QoL in 46 patients (34 men, mean age: 50 +/- 12 years)
      with drug-refractory AF. QoL was assessed by Medical Outcomes Study Short Form-36
      (SF-36) and Symptom Checklist at baseline and 3-month after cryoablation, and
      compared with those in a sex-age matched normal control. At 3-month follow-up, 24
      of 46 patients (52%) had no recurrence of AF, including 11 patients who were not
      taking antiarrhythmic drugs. At baseline, patients with AF had significantly
      lower QoL scores in overall and in 5/8 subscales of SF-36 than the sex-age
      matched control group (P < 0.05). In patients with successful outcome after
      cryoablation showed a significant improvement in overall and in 5/8 subscales of
      SF-36 QoL scores have significantly increased as compared with the baseline (P <
      0.05). Furthermore, their QoL scores in overall and in 6/8 subscales of SF-36
      were similar to the sex-age matched control group (P > 0.05). The Symptom
      Checklist also showed significant reduction in both the symptoms frequency scores
      and symptoms severity scores at 3-month follow-up as compared with baseline (P <
      0.05). CONCLUSIONS: Successful PV isolation using transvenous catheter
      cryoablation is associated with significant reduction in the frequency and
      severity of AF symptoms and improvement in the general QoL, reaching the levels
      of normal controls.

PMID- 15869675
TI  - Prevalence of venous anatomic variants and occlusion among patients undergoing
      implantation of transvenous leads.
AB  - BACKGROUND: The implantation of transvenous leads may be prohibited by venous
      occlusion or anatomical variants. The prevalence of these conditions among
      patients undergoing transvenous pacing or implantable cardioverter defibrillator
      (ICD) leads implantation has not been systematically studied. This study examined
      the prevalence of venous anatomic variants and/or venous occlusion, and related
      risk factors, prior to lead implantation. METHOD: The study included 273
      consecutive patients scheduled for implantation of transvenous pacing or ICD
      leads. Before the procedure, the venous network of arms, neck, and thorax was
      evaluated by bilateral intravenous digital subtraction angiography (DSA).
      RESULTS: Complete venous occlusion associated with developed collateral
      circulation was observed in 12 patients (4.4%); at the site of the left
      innominate vein in 9, left subclavian vein in 2, and right subclavian vein in 1
      patient. Of 12 patients with venous occlusion, 7 patients had a history of prior
      surgical procedure. A persistent left superior vena cava was observed in 1
      patient (0.4%). The presence of abnormal findings on DSA was significantly higher
      on the left than the right side (P < 0.001). The cardio-thoracic ratio (CTR) was
      significantly greater in patients with venous occlusions than patients with
      normal circulation (P = 0.012). CONCLUSIONS: Asymptomatic venous abnormalities
      are not rare among patients requiring transvenous pacing lead implantation.
      Careful attention should be paid when implanting pacing or ICD leads from the
      left side, especially in patients with an increased CTR or history of prior
      insertion for central venous catheter.

PMID- 15869676
TI  - Multiple reentrant tachycardias in a patient with WPW syndrome.

PMID- 15869677
TI  - Ventricular asystole during atrial antitachycardia pacing by implanted
      cardioverter-defibrillator.

PMID- 15869678
TI  - Alternative energy sources for the ablation of arrhythmias.

PMID- 15869679
TI  - The surgeon's dilemma--retirement.

PMID- 15869680
TI  - Reconstruction of Hyman's second pacemaker.
AB  - Though journal articles and newspaper reports suggest that three Hyman pacemakers
      existed or were intended; a patent, descriptive photographs and a written
      description of an earlier model and only a photograph of a later model exist. A
      replica of the earlier has been made based on the patent and description, and a
      new replica of the second based on a critical deconstruction and analysis of the
      photograph of the second with a modern circuit duplicating the function of the
      earlier circuit. Both replicas were "operational" in that stimuli were mimicked
      though not delivered and neither could under any circumstances actually
      resuscitate the heart. The design and construction of the second Hyman pacemaker
      are presented.

PMID- 15869681
TI  - Kearns-Sayre syndrome: a case report and review of cardiovascular complications.
AB  - Kearns-Sayre syndrome (KSS) is a rare genetic abnormality. Classified as a
      mitochondrial cytopathy, the primary pathology of this syndrome is a disturbance
      of mitochondrial DNA, which codes for the proteins required for the respiratory
      chain reaction. Onset occurs before age 20, and is manifest as chronic
      progressive external ophthalmoplegia and retinal degeneration. Management issues
      of KSS include prophylactic cardiac pacing for conduction defects, which has been
      shown to improve survival. Other clinical considerations relate to dietary
      supplements to attempt to control the progressive effects of the disease.

PMID- 15869682
TI  - Situational syncope induced by belching.
AB  - We describe a case of situational syncope induced by belching. The patient showed
      severe syncope with a high-degree atrioventricular block just after belching, but
      has not experienced syncope or dizziness over a 3-month follow-up after permanent
      pacemaker implantation.

PMID- 15869683
TI  - Utility of echocardiographic tissue synchronization imaging to redirect left
      ventricular lead placement for improved cardiac resynchronization therapy.
AB  - An 80-year-old woman with severe symptomatic heart failure (ejection fraction of
      13%), and left bundle branch block (QRS duration of 160 ms) underwent cardiac
      resynchronization therapy (CRT). She had significant baseline dyssynchrony with a
      septal to posterior wall delay of 160 ms by echocardiographic tissue
      synchronization imaging (TSI). Despite exhaustive efforts, a stable posterior
      lateral coronary vein lead position could not be achieved with the standard
      percutaneous approach, resulting in anterior coronary vein lead placement. This
      resulted in no improvement in the patient's symptoms or ventricular function.
      Follow-up TSI revealed earlier activation of the anteroseptal site and worsened
      dyssynchrony with septal to posterior wall delay of now 290 ms. This information
      prompted surgical revision of the left ventricular (LV) lead position via limited
      thoracotomy and posterior-lateral epicardial lead implantation. Pacing at the new
      lead site resulted in a 30% increase in stroke volume and symptomatic
      improvement. TSI in this case redirected lead position in a clinical
      nonresponder, resulting in a favorable response to CRT.

PMID- 15869684
TI  - Pneumopericardium and pneumothorax after permanent pacemaker implantation.
AB  - We present a patient with chronic obstructive pulmonary disease who developed
      discomfort 2 days after dual-chamber pacemaker implantation via the left cephalic
      vein approach. The pacer was placed with active-fixation leads without obvious
      complications. A computed tomography (CT) scan taken in the emergency room showed
      right pneumothorax and associated pneumopericardium without pneumomediastinum. A
      three-dimensional reconstruction of CT images confirmed the atrial lead
      protruding into the pleural space. This lead likely ruptured a bulla causing a
      pneumothorax followed by pneumopericardium through a pleuro-pericardial
      communication. Chest tube placement relieved both pneumothorax and
      pneumopericardium without the need for atrial lead extraction.

PMID- 15869685
TI  - Accidental transarterial implantation of dual chamber pacemaker leads in the left
      ventricle and the right coronary artery.
AB  - Implantation of permanent pacemaker systems is associated with a low rate of
      complications. The case of a 72-year-old woman is described who suffered from a
      cluster of complications related to permanent pacemaker implantation. Besides
      major bleeding, requiring transfusion and pneumothorax, malposition of both
      pacemaker leads in the arterial system occurred, with the atrial lead screwed
      into the right coronary artery, with subsequent occlusion of the vessel and the
      ventricle lead placed in the left ventricle.

PMID- 15869686
TI  - QT interval prolongation and torsades de pointes due to a coadministration of
      metronidazole and amiodarone.
AB  - This report documents the occurrence of torsades de pointes (TdP) caused by
      marked QT interval prolongation in the case of a 71-year-old woman receiving both
      metronidazole and amiodarone for the treatment of pseudomembranous colitis and
      paroxysmal atrial fibrillation. The case highlights a previously unknown drug
      interaction. The role of inhibition of cytochrome P-450 CYP3A4 is discussed.

PMID- 15869687
TI  - A 'Reveal'ing diagnosis.
AB  - The present case report describes a 54-year-old woman with recurrent syncope of
      undetermined etiology. Despite several cardiological and neurological
      investigations, no firm diagnosis was established until an insertable loop
      recorder (REVEAL Plus Model 9526, Medtronic Inc., Minneapolis, MN, USA) revealed
      muscle twitch artifact secondary to a seizure disorder.

PMID- 15869688
TI  - Right ventricular outflow tract endocardial pacing complicated by intercostal
      muscle twitching.
AB  - A recipient of a dual-chamber pacing system, with a bipolar endocardial lead
      screwed into the right ventricular outflow tract (RVOT), developed intercostal
      muscle twitching. No lead perforation was identified. This observation suggests
      that meticulous attention should be paid to this potential complication when
      choosing the RVOT as a site of permanent endocardial pacing.

PMID- 15869691
TI  - An alternative to null-hypothesis significance tests.
AB  - The statistic p(rep) estimates the probability of replicating an effect. It
      captures traditional publication criteria for signal-to-noise ratio, while
      avoiding parametric inference and the resulting Bayesian dilemma. In concert with
      effect size and replication intervals, p(rep) provides all of the information now
      used in evaluating research, while avoiding many of the pitfalls of traditional
      statistical inference.

PMID- 15869692
TI  - Deciding to defect: the effects of video-game violence on cooperative behavior.
AB  - This experiment examined the effect of video-game violence on cooperative
      decision making. Participants (N= 48) were randomly assigned to play either a
      violent or a nonviolent version of the video game Doom in dyads. Following the
      video-game task, participants were separated and given an opportunity to choose
      to cooperate with their partner for mutual gain, withdraw from the interaction,
      or exploit their partner for their own benefit. Participants in the violent
      condition were significantly more likely to choose to exploit their partners than
      participants in the nonviolent condition. These findings suggest that playing
      violent video games may undermine prosocial motivation and promote exploitive
      behavior in social interactions.

PMID- 15869693
TI  - Distinctive processing underlies skilled memory.
AB  - Research on skilled memory has focused on organizational processes to the
      exclusion of item-specific processes, although theories of skilled memory do
      acknowledge the importance of both kinds of processes. Using the isolation
      methodology, we presented lists of American football team names to participants
      who had either a high or a low level of knowledge about American football. An
      isolation effect (greater recall of the target in the isolate list than in a
      homogeneous control list) was observed only with high-knowledge participants.
      When standard lists were used, an isolation effect was observed with both groups.
      These findings empirically validate the importance of both organizational and
      item-specific processing as the basis of distinctive processing underlying
      skilled memory performance.

PMID- 15869694
TI  - Do speakers avoid ambiguities during dialogue?
AB  - What affects speakers' production of ambiguous utterances in dialogue? They might
      consider ease of production for themselves, or ease of comprehension for their
      addressees. Previous research has demonstrated that ease of production plays a
      role in speakers' syntactic choices, but that ease of comprehension does not.
      However, such studies have not employed dialogues that involve role swapping on a
      turn-by-turn basis. In our experiment, participants alternated in giving and
      following instructions to move objects around on a grid. They tended to repeat
      the syntactic form just used by their interlocutor, reflecting sensitivity to
      ease of production. More interestingly, they were more likely to disambiguate
      their utterances when the visual context was potentially ambiguous than when it
      was not, reflecting sensitivity to ease of comprehension. We conclude that
      speakers pay attention to their beliefs about their addressees' ease of
      comprehension, in addition to considering ease of production for themselves.

PMID- 15869695
TI  - Gesture paves the way for language development.
AB  - In development, children often use gesture to communicate before they use words.
      The question is whether these gestures merely precede language development or are
      fundamentally tied to it. We examined 10 children making the transition from
      single words to two-word combinations and found that gesture had a tight relation
      to the children's lexical and syntactic development. First, a great many of the
      lexical items that each child produced initially in gesture later moved to that
      child's verbal lexicon. Second, children who were first to produce gesture-plus
      word combinations conveying two elements in a proposition (point at bird and say
      "nap") were also first to produce two-word combinations ("bird nap"). Changes in
      gesture thus not only predate but also predict changes in language, suggesting
      that early gesture may be paving the way for future developments in language.

PMID- 15869696
TI  - Labeling guides object individuation in 12-month-old infants.
AB  - A new manual search method was used to investigate the impact of naming on object
      individuation in 12-month-old infants. In Experiment 1, on a two-word trial, an
      experimenter looked into a box while the infant was watching and provided two
      labels (e.g., "Look, a fep!" and "Look, a wug!"). On a one-word trial, the
      experimenter instead repeated the same label (e.g., "Look, a zav!"). After the
      infant retrieved one object from the box, subsequent search behavior was
      recorded. Infants searched more persistently (i.e., for a longer duration) after
      hearing two labels than one, suggesting that hearing two labels led the infants
      to expect two objects inside the box. In Experiment 2, infants' search behavior
      did not differ depending on whether they heard one or two emotional expressions,
      suggesting that the facilitation effect observed in Experiment 1 may be specific
      to linguistic expressions. Thus, we provide the first evidence that infants as
      young as 12 months are able to use intentional and referential cues to guide
      their object representations. These findings also suggest that a rudimentary
      version of the mutual-exclusivity constraint may be functional by the end of the
      first year.

PMID- 15869697
TI  - Synchrony in the onset of mental-state reasoning: evidence from five cultures.
AB  - Over the past 20 years, developmental psychologists have shown considerable
      interest in the onset of a theory of mind, typically marked by children's ability
      to pass false-belief tasks. In Western cultures, children pass such tasks around
      the age of 5 years, with variations of the tasks producing small changes in the
      age at which they are passed. Knowing whether this age of transition is common
      across diverse cultures is important to understanding what causes this
      development. Cross-cultural studies have produced mixed findings, possibly
      because of varying methods used in different cultures. The present study used a
      single procedure to measure false-belief understanding in five cultures: Canada,
      India, Peru, Samoa, and Thailand. With a standardized procedure, we found
      synchrony in the onset of mentalistic reasoning, with children crossing the false
      belief milestone at approximately 5 years of age in every culture studied. The
      meaning of this synchrony for the origins of mental-state understanding is
      discussed.

PMID- 15869698
TI  - The development of cynicism.
AB  - Two experiments explored the development of cynicism by examining how children
      evaluate other people who make claims consistent or inconsistent with their self
      interests. In Experiment 1, kindergartners, second graders, and fourth graders
      heard stories with ambiguous conclusions in which characters made statements that
      were aligned either with or against self-interest. Older children took into
      account the self-interests of characters in determining how much to believe them:
      They discounted statements aligned with self-interest, whereas they accepted
      statements going against self-interest. Experiment 2 examined children's
      endorsement of three different explanations for potentially self-interested
      statements: lies, biases, and mistakes. Like adults, sixth graders endorsed lies
      and bias as plausible explanations for wrong statements aligned with self
      interest; younger children did not endorse bias. Implications for the development
      of cynicism and children's understanding of bias are discussed.

PMID- 15869699
TI  - You can't always get what you want: effortful control and children's responses to
      undesirable gifts.
AB  - This study examined individual differences in children's regulation of emotional
      expression after receiving desirable and undesirable gifts. Effortful control,
      the ability to suppress a dominant response in favor of a subdominant one, was
      measured using a battery of behavioral tasks. Reactions to the gifts were
      videotaped, and emotional expression was coded. Age predicted effortful control,
      but not emotional displays. Effortful control predicted similarity of children's
      displays of positive affect after receiving the two gifts. Specifically, children
      high in effortful control showed similar amounts of positive affect after
      receiving the desirable and undesirable gifts, whereas children low in effortful
      control showed less positive affect after receiving the undesirable gift than
      after receiving the desirable gift. Results are discussed in terms of temperament
      and the development of socially appropriate expressive behavior.

PMID- 15869700
TI  - Ironic effects of racial bias during interracial interactions.
AB  - Previous research has suggested that Blacks like White interaction partners who
      make an effort to appear unbiased more than those who do not. We tested the
      hypothesis that, ironically, Blacks perceive White interaction partners who are
      more racially biased more positively than less biased White partners, primarily
      because the former group must make more of an effort to control racial bias than
      the latter. White participants in this study completed the Implicit Association
      Test (IAT) as a measure of racial bias and then discussed race relations with
      either a White or a Black partner. Whites' IAT scores predicted how positively
      they were perceived by Black (but not White) interaction partners, and this
      relationship was mediated by Blacks' perceptions of how engaged the White
      participants were during the interaction. We discuss implications of the finding
      that Blacks may, ironically, prefer to interact with highly racially biased
      Whites, at least in short interactions.

PMID- 15869701
TI  - Deciphering the enigmatic face: the importance of facial dynamics in interpreting
      subtle facial expressions.
AB  - Most studies investigating the recognition of facial expressions have focused on
      static displays of intense expressions. Consequently, researchers may have
      underestimated the importance of motion in deciphering the subtle expressions
      that permeate real-life situations. In two experiments, we examined the effect of
      motion on perception of subtle facial expressions and tested the hypotheses that
      motion improves affect judgment by (a) providing denser sampling of expressions,
      (b) providing dynamic information, (c) facilitating configural processing, and
      (d) enhancing the perception of change. Participants viewed faces depicting
      subtle facial expressions in four modes (single-static, multi-static, dynamic,
      and first-last). Experiment 1 demonstrated a robust effect of motion and
      suggested that this effect was due to the dynamic property of the expression.
      Experiment 2 showed that the beneficial effect of motion may be due more
      specifically to its role in perception of change. Together, these experiments
      demonstrated the importance of motion in identifying subtle facial expressions.

PMID- 15869702
TI  - Consuming now or later? The interactive effect of timing and attribute
      alignability.
AB  - Decisions are often temporally separated from their outcomes. Using theories of
      structural alignment and temporal construal, we examined how temporal distance
      and the associated shift in decision processes moderate susceptibility to context
      effects. Specifically, in two experiments (one hypothetical, one with real
      outcomes), we demonstrated that people attend more to nonalignable differences
      when the outcome of the decision is in the distant future than when it is in the
      near future. This shift in decision processes was found in preference and choice
      data, as well as coded written protocols. We further show that this temporal
      shift cannot be explained by differential involvement with the decision or by the
      feasibility and desirability of the attributes. Our findings establish temporal
      distance as an important moderator of structural alignment effects and also
      extend the implications of temporal construal theory beyond the nature of the
      attributes to the structural relationships among attributes.

PMID- 15869704
TI  - Perceived barriers for treatment of chronic heart failure in general practice;
      are they affecting performance?
AB  - BACKGROUND: The aim of this study is to determine to what extent barriers
      perceived by general practitioners (GPs) for prescribing angiotensin-converting
      enzyme inhibitors (ACE-I) in chronic heart failure (CHF) patients are related to
      underuse and underdosing of these drugs in actual practice. METHODS: Barriers
      were assessed with a semi-structured questionnaire. Prescribing data were
      extracted from GPs' computerised medical records for a random sample of their CHF
      patients. Relations between barriers and prescribing behaviour were assessed by
      means of Spearman rank correlation and multivariate regression modelling.
      RESULTS: GPs prescribed ACE-I to 45% of their patients and had previously
      initiated such treatment in an additional 3.5%, in an average standardised dose
      of 13.5 mg. They perceived a median of four barriers in prescribing ACE-I or
      optimising ACE-I dose. Many GPs found it difficult to change treatment initiated
      by a cardiologist. Furthermore, initiating ACE-I in patients already using a
      diuretic or stable on their current medication was perceived as barrier.
      Titrating the ACE-I dose was seen as difficult by more than half of the GPs. No
      significant relationships could be found between the barriers perceived and
      actual ACE-I prescribing. Regarding ACE-I dosing, the few GPs who did not agree
      that the ACE-I should be as high as possible prescribed higher ACE-I doses.
      CONCLUSION: Variation between GPs in prescribing ACE-I for CHF cannot be
      explained by differences in the barriers they perceive. Tailor-made interventions
      targeting only those doctors that perceive a specific barrier will therefore not
      be an efficient approach to improve quality of care.

PMID- 15869705
TI  - Lepidium meyenii (Maca) increases litter size in normal adult female mice.
AB  - BACKGROUND: Lepidium meyenii, known as Maca, grows exclusively in the Peruvian
      Andes over 4000 m altitude. It has been used traditionally to increase fertility.
      Previous scientific studies have demonstrated that Maca increases spermatogenesis
      and epididymal sperm count. The present study was aimed to investigate the
      effects of Maca on several fertility parameters of female mice at reproductive
      age. METHODS: Adult female Balb/C mice were divided at random into three main
      groups: i) Reproductive indexes group, ii) Implantation sites group and iii)
      Assessment of uterine weight in ovariectomized mice. Animals received an aqueous
      extract of lyophilized Yellow Maca (1 g/Kg BW) or vehicle orally as treatment. In
      the fertility indexes study, animals received the treatment before, during and
      after gestation. The fertility index, gestation index, post-natal viability
      index, weaning viability index and sex ratio were calculated. Sexual maturation
      was evaluated in the female pups by the vaginal opening (VO) day. In the
      implantation study, females were checked for implantation sites at gestation day
      7 and the embryos were counted. In ovariectomized mice, the uterine weight was
      recorded at the end of treatment. RESULTS: Implantation sites were similar in
      mice treated with Maca and in controls. All reproductive indexes were similar in
      both groups of treatment. The number of pups per dam at birth and at postnatal
      day 4 was significantly higher in the group treated with Maca. VO day occurred
      earlier as litter size was smaller. Maca did not affect VO day. In ovariectomized
      mice, the treatment with Maca increased significantly the uterine weights in
      comparison to their respective control group. CONCLUSION: Administration of
      aqueous extract of Yellow Maca to adult female mice increases the litter size.
      Moreover, this treatment increases the uterine weight in ovariectomized animals.
      Our study confirms for the first time some of the traditional uses of Maca to
      enhance female fertility.

PMID- 15869706
TI  - Clinical and biological characteristics of cervical neoplasias with FGFR3
      mutation.
AB  - BACKGROUND: We have previously reported activating mutations of the gene coding
      for the fibroblast growth factor receptor 3 (FGFR3) in invasive cervical
      carcinoma. To further analyze the role of FGFR3 in cervical tumor progression, we
      extended our study to screen a total of 75 invasive tumors and 80 cervical
      intraepithelial neoplasias (40 low-grade and 40 high-grade lesions). RESULTS:
      Using single strand conformation polymorphism (SSCP) followed by DNA sequencing,
      we found FGFR3 mutation (S249C in all cases) in 5% of invasive cervical
      carcinomas and no mutation in intraepithelial lesions. These results suggest
      that, unlike in bladder carcinoma, FGFR3 mutation does not or rarely occur in non
      invasive lesions. Compared to patients with wildtype FGFR3 tumor, patients with
      S249C FGFR3 mutated tumors were older (mean age 64 vs. 49.4 years, P = 0.02), and
      were more likely to be associated with a non-16/18 HPV type in their tumor. Gene
      expression analysis demonstrated that FGFR3 mutated tumors were associated with
      higher FGFR3b mRNA expression levels compared to wildtype FGFR3 tumors.
      Supervised analysis of Affymetrix expression data identified a significant number
      of genes specifically differentially expressed in tumors with respect to FGFR3
      mutation status. CONCLUSION: This study suggest that tumors with FGFR3 mutation
      appear to have distinctive clinical and biological characteristics that may help
      in defining a population of patients for FGFR3 mutation screening.

PMID- 15869703
TI  - Mechanisms of lipid malabsorption in Cystic Fibrosis: the impact of essential
      fatty acids deficiency.
AB  - Transport mechanisms, whereby alimentary lipids are digested and packaged into
      small emulsion particles that enter intestinal cells to be translocated to the
      plasma in the form of chylomicrons, are impaired in cystic fibrosis. The purpose
      of this paper is to focus on defects that are related to intraluminal and
      intracellular events in this life-limiting genetic disorder. Specific evidence is
      presented to highlight the relationship between fat malabsorption and essential
      fatty acid deficiency commonly found in patients with cystic fibrosis that are
      often related to the genotype. Given the interdependency of pulmonary disease,
      pancreatic insufficiency and nutritional status, greater attention should be paid
      to the optimal correction of fat malabsorption and essential fatty acid
      deficiency in order to improve the quality of life and extend the life span of
      patients with cystic fibrosis.

PMID- 15869707
TI  - The effects of amisulpride on five dimensions of psychopathology in patients with
      schizophrenia: a prospective open-label study.
AB  - BACKGROUND: The efficacy of antipsychotics can be evaluated using the dimensional
      models of schizophrenic symptoms. The D2/D3-selective antagonist amisulpride has
      shown similar efficacy and tolerability to other atypical antipsychotics. The aim
      of the present study was to determine the efficacy of amisulpride on the
      dimensional model of schizophrenic symptoms and tolerability in latin
      schizophrenic patients. METHOD: Eighty schizophrenic patients were enrolled and
      70 completed a prospective open-label 3-month study with amisulpride. The
      schizophrenic symptoms, psychosocial functioning and side-effects were evaluated
      with standardized scales. RESULTS: The patients showed significant improvement in
      the five dimensions evaluated. Amisulpride (median final dose 357.1 mg/d) was
      well-tolerated without treatment-emergent extrapyramidal side-effects.
      CONCLUSION: Amisulpride showed efficacy on different psychopathological
      dimensions and was well tolerated, leading to consider this drug a first line
      choice for the treatment of schizophrenia.

PMID- 15869708
TI  - Refined repetitive sequence searches utilizing a fast hash function and cross
      species information retrievals.
AB  - BACKGROUND: Searching for small tandem/disperse repetitive DNA sequences
      streamlines many biomedical research processes. For instance, whole genomic array
      analysis in yeast has revealed 22 PHO-regulated genes. The promoter regions of
      all but one of them contain at least one of the two core Pho4p binding sites,
      CACGTG and CACGTT. In humans, microsatellites play a role in a number of rare
      neurodegenerative diseases such as spinocerebellar ataxia type 1 (SCA1). SCA1 is
      a hereditary neurodegenerative disease caused by an expanded CAG repeat in the
      coding sequence of the gene. In bacterial pathogens, microsatellites are proposed
      to regulate expression of some virulence factors. For example, bacteria commonly
      generate intra-strain diversity through phase variation which is strongly
      associated with virulence determinants. A recent analysis of the complete
      sequences of the Helicobacter pylori strains 26695 and J99 has identified 46
      putative phase-variable genes among the two genomes through their association
      with homopolymeric tracts and dinucleotide repeats. Life scientists are
      increasingly interested in studying the function of small sequences of DNA.
      However, current search algorithms often generate thousands of matches -- most of
      which are irrelevant to the researcher. RESULTS: We present our hash function as
      well as our search algorithm to locate small sequences of DNA within multiple
      genomes. Our system applies information retrieval algorithms to discover
      knowledge of cross-species conservation of repeat sequences. We discuss our
      incorporation of the Gene Ontology (GO) database into these algorithms. We
      conduct an exhaustive time analysis of our system for various repetitive sequence
      lengths. For instance, a search for eight bases of sequence within 3.224 GBases
      on 49 different chromosomes takes 1.147 seconds on average. To illustrate the
      relevance of the search results, we conduct a search with and without added
      annotation terms for the yeast Pho4p binding sites, CACGTG and CACGTT. Also, a
      cross-species search is presented to illustrate how potential hidden correlations
      in genomic data can be quickly discerned. The findings in one species are used as
      a catalyst to discover something new in another species. These experiments also
      demonstrate that our system performs well while searching multiple genomes --
      without the main memory constraints present in other systems. CONCLUSION: We
      present a time-efficient algorithm to locate small segments of DNA and
      concurrently to search the annotation data accompanying the sequence. Genome-wide
      searches for short sequences often return hundreds of hits. Our experiments show
      that subsequently searching the annotation data can refine and focus the results
      for the user. Our algorithms are also space-efficient in terms of main memory
      requirements. Source code is available upon request.

PMID- 15869710
TI  - PathwayVoyager: pathway mapping using the Kyoto Encyclopedia of Genes and Genomes
      (KEGG) database.
AB  - BACKGROUND: Equally important and challenging as genome annotation, is the
      subsequent classification of predicted genes into their respective pathways. The
      Kyoto Encyclopedia of Genes and Genomes (KEGG) represents a database consisting
      of known genes and their respective biochemical functionalities. Although
      accessible online, analyses of multiple genes are time consuming and are not
      suitable for analyzing data sets that are proprietary. RESULTS: Presented here is
      a new software solution that utilizes the KEGG online database for pathway
      mapping of partial and whole prokaryotic genomes. PathwayVoyager retrieves user
      defined subsets of the KEGG database and stores the data as local, blast
      formatted databases. Previously selected datasets can be re-used, reducing run
      time significantly. Whole or partial genomes can be automatically analyzed using
      NCBI's BlastP algorithm and ORFs with similarities below the user-defined
      threshold will be marked on pathway maps. Multiple gene hits are sorted by
      similarity. Since no sequence information is transmitted over the Internet,
      PathwayVoyager is an ideal solution for pathway mapping and reconstruction of
      confidential DNA sequence data. CONCLUSION: PathwayVoyager represents an
      alternative approach to many already existing, more complex pathway
      reconstructions software solutions. This software does not require any dedicated
      hardware or software and is flexible and straightforward to use. It is ideally
      suited for environments where analyses on variable datasets are desired.

PMID- 15869709
TI  - Parallel organization of contralateral and ipsilateral prefrontal cortical
      projections in the rhesus monkey.
AB  - BACKGROUND: The neocortical commissures have a fundamental role in functional
      integration across the cerebral hemispheres. We investigated whether commissural
      projections in prefrontal cortices are organized according to the same or
      different rules as those within the same hemisphere, by quantitatively comparing
      density, topography, and laminar origin of contralateral and ipsilateral
      projections, labeled after unilateral injection of retrograde tracers in
      prefrontal areas. RESULTS: Commissural projection neurons constituted less than
      one third of the ipsilateral. Nevertheless, projections from the two hemispheres
      were strongly correlated in topography and relative density. We investigated to
      what extent the distribution of contralateral projections depended on: (a)
      geographic proximity of projection areas to the area homotopic to the injection
      site; (b) the structural type of the linked areas, based on the number and
      neuronal density of their layers. Although both measures were good predictors,
      structural type was a comparatively stronger determinant of the relative
      distribution and density of projections. Ipsilateral projection neurons were
      distributed in the superficial (II-III) and deep (V-VI) layers, in proportions
      that varied across areas. In contrast, contralateral projection neurons were
      found mostly in the superficial layers, but still showed a gradient in their
      distribution within cortical layers that correlated significantly with cortical
      type, but not with geographic proximity to the homotopic area. CONCLUSION: The
      organization of ipsilateral and contralateral prefrontal projections is similar
      in topography and relative density, differing only by higher overall density and
      more widespread laminar origin of ipsilateral than contralateral projections. The
      projections on both sides are highly correlated with the structural architecture
      of the linked areas, and their remarkable organization is likely established by
      punctuated development of distinct cortical types. The preponderance of
      contralateral projections from layer III may be traced to the late development of
      the callosal system, whose function may be compromised in diseases that have
      their root late in ontogeny.

PMID- 15869711
TI  - Correction: Perivascular epithelioid cell tumor (PEComa) of the uterine cervix
      associated with intraabdominal "PEComatosis": A clinicopathological study with
      comparative genomic hybridization analysis.

PMID- 15869713
TI  - N-acetyl-L-cysteine ameliorates the inflammatory disease process in experimental
      autoimmune encephalomyelitis in Lewis rats.
AB  - We report that N-acetyl-L-cysteine (NAC) treatment blocked induction of TNF
      alpha, IL-1beta, IFN-gamma and iNOS in the CNS and attenuated clinical disease in
      the myelin basic protein induced model of experimental allergic encephalomyelitis
      (EAE) in Lewis rats. Infiltration of mononuclear cells into the CNS and induction
      of inflammatory cytokines and iNOS in multiple sclerosis (MS) and EAE have been
      implicated in subsequent disease progression and pathogenesis. To understand the
      mechanism of efficacy of NAC against EAE, we examined its effect on the
      production of cytokines and the infiltration of inflammatory cells into the CNS.
      NAC treatment attenuated the transmigration of mononuclear cells thereby
      lessening the neuroinflammatory disease. Splenocytes from NAC-treated EAE animals
      showed reduced IFN-gamma production, a Th1 cytokine and increased IL-10
      production, an anti-inflammatory cytokine. Further, splenocytes from NAC-treated
      EAE animals also showed decreased nitrite production when stimulated in vitro by
      LPS. These observations indicate that NAC treatment may be of therapeutic value
      in MS against the inflammatory disease process associated with the infiltration
      of activated mononuclear cells into the CNS.

PMID- 15869714
TI  - Evolution of temporal order in living organisms.
AB  - Circadian clocks are believed to have evolved in parallel with the geological
      history of the earth, and have since been fine-tuned under selection pressures
      imposed by cyclic factors in the environment. These clocks regulate a wide
      variety of behavioral and metabolic processes in many life forms. They enhance
      the fitness of organisms by improving their ability to efficiently anticipate
      periodic events in their external environments, especially periodic changes in
      light, temperature and humidity. Circadian clocks provide fitness advantage even
      to organisms living under constant conditions, such as those prevailing in the
      depth of oceans or in subterranean caves, perhaps by coordinating several
      metabolic processes in the internal milieu. Although the issue of adaptive
      significance of circadian rhythms has always remained central to circadian
      biology research, it has never been subjected to systematic and rigorous
      empirical validation. A few studies carried out on free-living animals under
      field conditions and simulated periodic and aperiodic conditions of the
      laboratory suggest that circadian rhythms are of adaptive value to their owners.
      However, most of these studies suffer from a number of drawbacks such as lack of
      population-level replication, lack of true controls and lack of adequate control
      on the genetic composition of the populations, which in many ways limits the
      potential insights gained from the studies. The present review is an effort to
      critically discuss studies that directly or indirectly touch upon the issue of
      adaptive significance of circadian rhythms and highlight some shortcomings that
      should be avoided while designing future experiments.

PMID- 15869715
TI  - Guanylic nucleotide starvation affects Saccharomyces cerevisiae mother-daughter
      separation and may be a signal for entry into quiescence.
AB  - BACKGROUND: Guanylic nucleotides are both macromolecules constituents and crucial
      regulators for a variety of cellular processes. Therefore, their intracellular
      concentration must be strictly controlled. Consistently both yeast and mammalian
      cells tightly correlate the transcription of genes encoding enzymes critical for
      guanylic nucleotides biosynthesis with the proliferation state of the cell
      population. RESULTS: To gain insight into the molecular relationships connecting
      intracellular guanylic nucleotide levels and cellular proliferation, we have
      studied the consequences of guanylic nucleotide limitation on Saccharomyces
      cerevisiae cell cycle progression. We first utilized mycophenolic acid, an
      immunosuppressive drug that specifically inhibits inosine monophosphate
      dehydrogenase, the enzyme catalyzing the first committed step in de novo GMP
      biosynthesis. To approach this system physiologically, we next developed yeast
      mutants for which the intracellular guanylic nucleotide pools can be modulated
      through changes of growth conditions. In both the pharmacological and genetic
      approaches, we found that guanylic nucleotide limitation generated a mother
      daughter separation defect, characterized by cells with two unseparated
      daughters. We then showed that this separation defect resulted from cell wall
      perturbations but not from impaired cytokinesis. Importantly, cells with similar
      separation defects were found in a wild type untreated yeast population entering
      quiescence upon nutrient limitation. CONCLUSION: Our results demonstrate that
      guanylic nucleotide limitation slows budding yeast cell cycle progression, with a
      severe pause in telophase. At the cellular level, guanylic nucleotide limitation
      causes the emergence of cells with two unseparated daughters. By fluorescence and
      electron microscopy, we demonstrate that this phenotype arises from defects in
      cell wall partition between mother and daughter cells. Because cells with two
      unseparated daughters are also observed in a wild type population entering
      quiescence, our results reinforce the hypothesis that guanylic nucleotide
      intracellular pools contribute to a signal regulating both cell proliferation and
      entry into quiescence.

PMID- 15869716
TI  - Interferon-gamma promotes abortion due to Brucella infection in pregnant mice.
AB  - BACKGROUND: The mechanisms of abortion induced by bacterial infection are largely
      unknown. In the present study, we investigated abortion induced by Brucella
      abortus, a causative agent of brucellosis and facultative intracellular pathogen,
      in a mouse model. RESULTS: High rates of abortion were observed for bacterial
      infection on day 4.5 of gestation, but not for other days. Regardless of whether
      fetuses were aborted or stayed alive, the transmission of bacteria into the fetus
      and bacterial replication in the placenta were observed. There was a higher
      degree of bacterial colonization in the placenta than in other organs and many
      bacteria were detected in trophoblast giant cells in the placenta. Intracellular
      growth-defective virB4 mutant and attenuated vaccine strain S19 did not induce
      abortion. In the case of abortion, around day 7.5 of gestation (period of
      placental development), transient induction of IFN-gamma production was observed
      for infection by the wild type strain, but not by the virB4 mutant and S19.
      Neutralization of IFN-gamma, whose production was induced by infection with B.
      abortus, served to prevent abortion. CONCLUSION: These results indicate that
      abortion induced by B. abortus infection is a result of transient IFN-gamma
      production during the period of placental development.

PMID- 15869717
TI  - Brief cognitive assessment in a UK population sample -- distributional properties
      and the relationship between the MMSE and an extended mental state examination.
AB  - BACKGROUND: Despite the MMSE's known flaws, it is still used extensively as both
      a screening instrument for dementia and a population measure of cognitive
      ability. The aim of this paper is to provide data on the distribution of MMSE
      scores in a representative sample from the UK population and to compare it with
      an extended cognitive assessment (EMSE) which covers a wider range of cognitive
      domains and provides a wider range of difficulty levels. METHODS: The MMSE and
      the EMSE were administered to over 12,000 participants at the screening stage of
      the MRC Cognitive Function and Ageing Study (MRC CFAS). MRC CFAS is a multi
      centre population-based study in England and Wales with respondents aged 65 years
      and older. RESULTS: Normative values on the MMSE and EMSE are presented by age
      group, sex and level of education. There are very large differences between age
      groups, with smaller differences seen between the sexes and by level of
      education. The EMSE extends the scores at the high end of the ability range, but
      is no better than the MMSE at differentiating between dementia and non-dementia.
      CONCLUSION: Population-derived norms are valuable for comparing an individual's
      score to the score that would be expected among the general population, given the
      individual's specific demographic characteristics.

PMID- 15869718
TI  - Practical guide to the management of osteoporosis in men with prostate cancer
      receiving androgen-deprivation therapy.

PMID- 15869719
TI  - Targeting osseous metastases: rationale and development of radio-immunotherapy
      for prostate cancer.
AB  - For patients with metastatic prostate cancer, bone is the primary site of tumor
      localization and the major cause of disease-related morbidity and mortality.
      Hormonal therapy and chemotherapy alone cannot eradicate disease harbored in
      bone. The delivery of radiotherapy to the reservoir of disease is an approach
      previously only achievable using bone-seeking radiopharmaceuticals. Now, however,
      with the identification of tumor-specific targets, antibodies are being used to
      deliver radiotherapy to these sites. In this article, we review the rationale
      behind this approach, the targets being explored, the radiation sources
      available, and the antibodies currently under clinical development.

PMID- 15869720
TI  - Biomarkers for the detection and prognosis of prostate cancer.
AB  - Recent studies have cast doubt on the reliability of serum total prostate
      specific antigen as a biomarker for the detection and prognosis of prostate
      cancer. Biomarkers that can identify those men at risk for clinically significant
      prostate cancer are desperately needed. The search for biomarkers that may
      improve the detection of biologically consequential prostate cancer is one of the
      most active areas under current investigation. In this review, we highlight some
      of these ongoing efforts. Proper validation of newly discovered biomarkers is of
      paramount importance.

PMID- 15869721
TI  - What's new in the field of prostate cancer chemoprevention?
AB  - Chemoprevention trials for several malignancies are completed, planned, or
      underway. Prostate cancer is one of the most common forms of cancer and
      understandably has received considerable recent attention as a potential target
      for chemoprevention. This article examines chemoprevention trials for prostate
      cancer, including the Prostate Cancer Prevention Trial, Selenium and Vitamin E
      Cancer Prevention Trial, and cyclooxygenase inhibitors in the prevention of
      prostate cancer.

PMID- 15869722
TI  - Local and systemic therapy for patients with metastatic prostate cancer: should
      the primary tumor be treated?
AB  - Data from well-designed, prospective clinical trials are lacking to support
      treatment of primary tumor in men diagnosed with metastatic prostate cancer.
      However, a growing body of evidence suggests that treatment of the primary tumor
      may enhance cancer control and survival in some men. This evidence is examined
      and recommendations are made for identifying patients with metastatic prostate
      cancer who may benefit from definitive treatment of the prostate tumor.

PMID- 15869723
TI  - Critical review of the efficacy and safety of cryotherapy of the prostate.
AB  - Modern cryoablation of the prostate is a procedure that has evolved since the
      early 1990s into a safer and more successful treatment of adenocarcinoma of the
      prostate. The improvement of this technique has taken place secondary to
      advancement in engineering, procedure refinement, temperature monitoring, and a
      better understanding of physiologic events during the freezing process. Long-term
      results are available that demonstrate durable efficacy equivalent to other
      therapies in low-risk groups. In moderate to high risk groups, results point
      toward equal to superior results than other standard therapies. New ideas on
      potency preservation using vacuum erection devices have improved men's return to
      function over the course of the postoperative year. Early morbidity issues, such
      as fistula formation and incontinence, have become much less problematic, with
      results between 0% and 1% in some series. Cryoablation of the prostate now offers
      significantly improved outcomes with a parallel decrease in morbidity.

PMID- 15869725
TI  - Complications of androgen-deprivation therapy in men with prostate cancer.
AB  - Androgen-deprivation therapy (ADT) is indicated for the treatment of metastatic
      prostate cancer and locally advanced disease. In addition to sexual side effects,
      long-term ADT results in several other changes, including hot flashes;
      gynecomastia; changes in body composition, metabolism, and the cardiovascular
      system; osteoporosis; anemia; psychiatric and cognitive problems; and fatigue and
      diminished quality of life. This review discusses these complications of ADT and
      treatments aimed at reducing them. It is important for clinicians to anticipate
      these effects and to initiate measures to prevent or minimize them in order to
      maintain quality of life in prostate cancer survivors.

PMID- 15869724
TI  - The efficacy of conventional external beam, three-dimensional conformal,
      intensity-modulated, particle beam radiation, and brachytherapy for localized
      prostate cancer.
AB  - Technologic advances in radiation treatment planning and delivery have generated
      popular interest in the different radiation therapy techniques used in treating
      patients with localized prostate cancer. Throughout the past decade, high-energy
      (> 4 MV) linear accelerators have largely replaced Cobalt machines in external
      beam radiation therapy (EBRT) delivery. Conventional EBRT has been used to treat
      prostate cancer successfully since the 1950s. By switching to computed tomography
      based planning, three-dimensional conformal radiation therapy provides better
      relative conformality of dose than does conventional EBRT. Intensity-modulated
      radiation therapy (IMRT) has further refined dose conformality by spreading the
      low-dose region to a larger volume. However, the potential long-term risks of
      larger volumes of normal tissues receiving low doses of radiation in IMRT are
      unknown. Particle-beam radiation therapy offers unique dose distributions and
      characteristics with higher relative biologic effect and linear energy transfer.
      Transperineal prostate brachytherapy offers the shortest treatment time with
      equivalent efficacy without significant risk of radiation exposure. The addition
      of hormonal therapy to radiation therapy has been shown to improve the outcome of
      radiation therapy.

PMID- 15869727
TI  - Chemotherapy agents and timing of chemotherapy in prostate cancer management.
AB  - In 2005, it is estimated that more than 30,000 men will die from metastatic
      hormone-refractory prostate cancer. For decades, no chemotherapeutic agent
      demonstrated a survival benefit in these patients, although two randomized
      clinical trials demonstrated a clear palliative benefit using mitoxantrone
      combined with a corticosteroid. However, beginning in 1999, a series of phase-2
      trials were performed using docetaxel, either as a single agent or in combination
      with estramustine. Preliminary data implied a survival improvement, with median
      survivals reported to be 14 to 23 months. Prostate-specific antigen levels
      dropped by more than 50% in 38% to 48% of patients treated with docetaxel. These
      findings were confirmed in two phase-3 randomized trials in which docetaxel with
      and without estramustine have demonstrated a survival benefit using chemotherapy
      in the treatment of hormone-refractory prostate cancer.

PMID- 15869726
TI  - Preventing and treating the complications of hormone therapy.
AB  - Hormonal manipulation in the form of androgen-deprivation therapy for prostate
      cancer was introduced by Huggins and Hodges in 1941 and resulted in a Nobel Prize
      in 1966. Hormonal therapy initially had been used in metastatic prostate cancer,
      but the indications have been expanded including failed local therapy, locally
      advanced prostate cancer, and neoadjuvant or adjuvant therapy in high-risk
      localized prostate cancer. In view of the magnitude of the problem of prostate
      cancer and relatively frequent use of hormonal manipulation, it is important for
      clinicians to be aware of common side effects, prevention, and treatment to
      improve quality of life and reduce morbidity and mortality in patients with
      prostate cancer. This review focuses on the common side effects of hormonal
      treatment such as osteoporosis, anemia, hot flashes, erectile dysfunction, muscle
      wasting, gynecomastia, decline in cognitive function, depression, increase in
      body fat and metabolic changes, and their prevention and treatment.

PMID- 15869728
TI  - Multidisciplinary management of prostate malignancy.
AB  - Most urologic malignancies are diagnosed initially and managed by urologists.
      However, better outcomes may be attained by integrating the surgical, medical,
      and radiologic disciplines. The primary care physician remains an important
      cornerstone whose talents should not be underestimated in the overall patient
      management scheme. Additional services such as endocrinology, physical therapy,
      pain control, hospice, nutrition, biofeedback, and hyperbarics, among others,
      should be considered in the overall health care team. The organization of the
      team, including definition of the duties of key personnel and even the physical
      framework of the clinic, contribute to its success in treating patients with
      prostate cancer. Pitfalls of the process also are discussed in this article.

PMID- 15869729
TI  - Dendritic cells in melanoma immunotherapy.
AB  - No consensus exists regarding optimal systemic treatment for melanoma in the
      adjuvant or metastatic disease setting. Dendritic cell vaccine therapy, though
      investigational at present, offers very promising preliminary data that warrant
      exploration, and patients with existing disease and those seeking adjuvant
      treatment should evaluate open protocols using this strategy.

PMID- 15869730
TI  - Treatment of metastatic malignant melanoma.
AB  - The rapid increase in incidence of malignant melanoma has not been associated
      with better therapeutic options over the years. Single-agent chemotherapy or
      immunotherapy remain the treatments of choice when systemic therapy is offered.
      Dacarbazine (DTIC) is the chemotherapy of choice with a response rate of 16%.
      Other chemotherapies, including cisplatinum, paclitaxel, docetaxel and the DTIC
      analogue temozolomide, have shown activity in this disease. Based on their single
      agent activity, several combination chemotherapies have been investigated with
      preliminary results that appeared promising. However, in randomized phase III
      trials the two most active chemotherapy combination regimens, cisplatin,
      vinblastine, and DTIC (CVD) and the Dartmouth regimen (DTIC, cisplatin,
      bischloroethylnitrosourea , and tamoxifen), did not prove to be superior to
      single-agent DTIC for overall survival. Immunotherapy with either interleukin
      (IL)-2 or interferon (IFN) has demonstrated response rates of 10% to 15% in
      appropriately selected patients. In patients who achieve a complete response,
      responses can be of greater durability than those with chemotherapy. However, IL
      2 and IFN administration are associated with multiple side effects, and only
      physicians experienced in the management of such therapies should administer
      them. The potential benefit of combining chemotherapy with immunotherapy has led
      to multiple phase II trials of biochemotherapy that appeared to be associated
      with higher response rates and longer median survivals. However, several phase
      III trials have been completed that have not consistently demonstrated an
      improvement in either response rates or overall survival, and these approaches to
      therapy cannot be routinely recommended outside the context of a clinical trial.
      The surgical resection of isolated metastatic disease has demonstrated an
      important palliative benefit in those patients who present with solitary single
      organ disease with the exception of the liver. Radiation has an important role in
      the palliative management of brain metastasis and symptomatic bony metastasis.
      Both stereotactic radiosurgery and whole brain radiotherapy have been used alone
      and in combination to benefit patients in this troubling clinical circumstance.
      Isolated limb perfusion and a newer technique, isolated limb infusion have
      demonstrated high response rates for those uncommon patients who develop
      recurrent disease isolated to a limb. In our opinion, if complete metastasectomy
      is not feasible and in the absence of brain metastases, single-agent IL-2 is a
      good initial treatment choice in appropriately selected patients. Single-agent
      chemotherapy with DTIC is the treatment of choice for patients who are not
      candidates for IL-2. Adoptive immunotherapy combining nonmyeloablative
      chemotherapy with high-dose IL-2 is a potentially promising therapeutic strategy
      under investigation. Targeted therapy is also an area of promising development as
      single agents, in combination, and combined with chemotherapy. The latter will be
      the focus of at least one upcoming cooperative group phase III trial.

PMID- 15869731
TI  - Prolymphocytic leukemia.
AB  - Prolymphocytic leukemia is a rare chronic lymphoproliferative disorder that
      includes two subtypes, B cell and T cell, each with its own distinct clinical,
      laboratory and pathological features. T-cell prolymphocytic leukemia has an
      aggressive course with short median survival and poor response to chemotherapy.
      With the use of the purine analogue pentostatin more than half of patients will
      have a major response and a minority will have a complete remission, usually
      lasting months. With the introduction of alemtuzumab, most patients who
      progressed despite treatment with pentostatin had a major response with a
      complete remission rate higher than that obtained with pentostatin when used as a
      first line. Unfortunately, progression still follows shortly. We recommend
      alemtuzumab as initial therapy and offer stem cell transplant (SCT) to selected
      young, healthy patients who respond. Although B-cell prolymphocytic leukemia is
      also a progressive disease, some patients can achieve a prolonged progression
      free-survival with fludarabine. Patients presenting with massive splenomegaly may
      be effectively palliated with splenic irradiation or splenectomy. Rituximab is a
      promising agent and further investigations are warranted to better define its
      role in treatment of this disorder.

PMID- 15869732
TI  - Pediatric myelodysplastic syndromes.
AB  - A new classification of myelodysplastic and myeloproliferative diseases in
      childhood has greatly facilitated the diagnosis of these uncommon disorders.
      Because hematopoietic stem cell transplantation (HSCT) can cure more than half of
      the affected children, palliative treatment strategies often applied in adult
      myelodysplastic syndrome (MDS) are of little importance in pediatric MDS.
      Unraveling some of the underlying genetic factors predisposing to MDS at a young
      age may give important insights into leukemogenesis in the elderly.

PMID- 15869733
TI  - Genetics and molecular biology of chronic lymphocytic leukemia.
AB  - B cell chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease
      characterized by accumulation of malignant CD5+ B cells. Multiple molecular
      events likely contribute to malignant transformation; no single genetic
      abnormality or event has been shown to be responsible for development of the
      disease. Significant advances have recently been made towards understanding the
      genetic and molecular basis for the etiology and clinical course of CLL. Our
      current understanding is only now bringing us to the point where we can use this
      information in management and in developing new therapies for patients with CLL.
      Familial clustering of CLL cases is not uncommon and implicates a genetic basis
      for the development of the disease in some individuals. Potential interventions
      in this instance could employ strategies of gene transfer or gene therapy to
      correct genetic defects or strategies of chemoprevention, none of which is
      currently under investigation. Greater potential for therapeutic intervention
      rests with targeting molecular aberrations and altered gene expression in
      leukemia cells, for example, over expression of the anti-apoptotic proteins of
      the Bcl-2 family. CLL follows a variable clinical course, with some patients not
      needing treatment for many years and responding to therapy completely and
      repeatedly. Other patients have rapidly progressive disease that is refractory to
      currently available agents and they quickly succumb to their disease. One major
      recent advance has been the identification of molecular and genetic prognostic
      factors that can be used in early-stage patients to identify those likely to
      rapidly progress. This affords the opportunity to tailor management for patients
      based on the predictable aggressiveness of their disease. Molecular and genetic
      findings are increasingly influencing management decisions in CLL. Bone marrow
      transplantation may be considered for a patient with unfavorable prognostic
      features earlier than for a patient with favorable features and same clinical
      stage of disease. It is likely that these genetic and molecular-based factors
      will be targets of new treatment modalities that fundamentally change the
      management of this disease. In this review we detail the current understanding of
      the genetics and molecular biology of CLL and introduce potentials for
      therapeutic intervention.

PMID- 15869734
TI  - Current status of stem cell transplantation for multiple myeloma.
AB  - Stem cell transplantation for myeloma has become a standard of care for newly
      diagnosed patients. Current evidence favors tandem transplants for those patients
      not achieving a complete or very good partial response (<90%) after the first
      transplant. Transplantation is safe and has been shown to prolong survival even
      in patients 65 to 70 years of age. Whether the new agents thalidomide,
      lenalidomide, and bortezomib will have an impact on the survival advantage of
      stem cell transplantation is unknown.

PMID- 15869735
TI  - Treatment of myeloma in patients not eligible for transplantation.
AB  - Multiple myeloma (MM) remains an incurable disease for most patients, with a
      median survival of 4 to 5 years. High-dose chemotherapy followed by
      transplantation has resulted in improvement in response rates and survival
      compared with conventional therapy, but relapse is nearly universal and not all
      patients are candidates for this option of aggressive treatment. Standard
      therapeutic strategies for newly diagnosed patients not eligible for
      transplantation include pulsed high-dose dexamethasone, melphalan with
      prednisone, and vincristine in combination with doxorubicin and dexamethasone, as
      well as other combinations of alkylating agents. Emerging therapies under
      clinical investigation for first-line therapy include thalidomide, the
      thalidomide analog lenalidomide, and the proteasome inhibitor bortezomib alone
      and in combination with other agents, particularly dexamethasone. At an interim
      analysis, thalidomide combined with melphalan and prednisone was shown to induce
      a complete or near complete remission (CR) rate of 28% and overall
      (complete+partial) response rate of 77% in elderly patients generally not
      eligible for transplantation. These results are comparable to those obtained with
      high-dose therapy and may obviate transplantation in these patients. Induction
      therapy with bortezomib-based combinations induces complete and near complete
      remissions in a similar proportion of patients. These regimens include bortezomib
      and dexamethasone alone and in combination with doxorubicin, thalidomide, or
      melphalan. Use of thalidomide or bortezomib does not preclude stem cell harvest.
      Survival benefits need to be firmly established before these novel regimens
      emerge as the new standard of care for newly diagnosed disease. However, front
      line treatment with combinations involving these agents is a promising strategy
      that may improve the standard of care for patients both eligible and ineligible
      for stem cell transplantation.

PMID- 15869736
TI  - Treatment of Castleman's disease.
AB  - Castleman's disease (CD) was first described in 1954 and further defined in 1956
      by Castleman. Since then much has been learned about the heterogeneity of this
      condition. Subsequently, three pathologic classifications have been developed
      (hyaline vascular variant, plasma cell variant, and mixed variant) and two
      clinical classifications (unicentric [unifocal or localized] and multicentric
      [multifocal or generalized]). The pathology found with the unicentric
      presentation is most commonly that of the HV variant. It responds well to
      surgical resection and is associated with a benign course. The multicentric
      presentation is rarely composed of lymph nodes with HV pathology, but rather with
      the plasma cell or mixed pathology. This presentation requires systemic therapy
      and prognosis is guarded. Associated systemic symptoms are common. There is an
      increased incidence of CD in patients with HIV. The human herpes virus-8 is
      associated with nearly all of the HIV-associated CD cases and nearly 50% of non
      HIV cases. Interleukin (IL)-6 has also been shown to play a significant role in
      the pathogenesis of the disease. Paraneoplastic and autoimmune entities are not
      uncommon in the disorder. Variable benefit has been achieved with single agent
      chemotherapy, combination chemotherapy, interferon (IFN)-alpha, rituximab, anti
      IL-6 receptor antibodies, and thalidomide. Patients with CD are at increased risk
      for developing frank malignant lymphoma.

PMID- 15869737
TI  - Comprehensive analysis of vehicle-pedestrian crashes at intersections in Florida.
AB  - This study analyzes vehicle-pedestrian crashes at intersections in Florida over 4
      years, 1999-2002. The study identifies the group of drivers and pedestrians, and
      traffic and environmental characteristics that are correlated with high
      pedestrian crashes using log-linear models. The study also estimates the
      likelihood of pedestrian injury severity when pedestrians are involved in crashes
      using an ordered probit model. To better reflect pedestrian crash risk, a logical
      measure of exposure is developed using the information on individual walking
      trips in the household travel survey. Lastly, the impact of average traffic
      volume on pedestrian crashes is examined. As a result of the analysis, it was
      found that pedestrian and driver demographic factors, and road geometric, traffic
      and environment conditions are closely related to the frequency and injury
      severity of pedestrian crashes. Higher average traffic volume at intersections
      increases the number of pedestrian crashes; however, the rate of increase is
      steeper at lower values of average traffic volume. Based on the findings in the
      analysis, some countermeasures are recommended to improve pedestrian safety.

PMID- 15869738
TI  - In intact leaves, the maximum fluorescence level (F(M)) is independent of the
      redox state of the plastoquinone pool: a DCMU-inhibition study.
AB  - The effects of DCMU (3-(3',4'-dichlorophenyl)-1,1-dimethylurea) on the
      fluorescence induction transient (OJIP) in higher plants were re-investigated. We
      found that the initial (F(0)) and maximum (F(M)) fluorescence levels of DCMU
      treated leaves do not change relative to controls when the treatment is done in
      complete darkness and DCMU is allowed to diffuse slowly into the leaves either by
      submersion or by application via the stem. Simultaneous 820 nm transmission
      measurements (a measure of electron flow through Photosystem I) showed that in
      the DCMU-treated samples, the plastoquinone pool remained oxidized during the
      light pulses whereas in uninhibited leaves, the F(M) level coincided with a fully
      reduced electron transport chain. The identical F(M) values with and without DCMU
      indicate that in intact leaves, the F(M) value is independent of the redox state
      of the plastoquinone pool. We also show that (i) the generally observed F(0)
      increase is probably due to the presence of (even very weak) light during the
      DCMU treatment, (ii) vacuum infiltration of leaf discs leads to a drastic
      decrease of the fluorescence yield, and in DCMU-treated samples, the F(M)
      decreases to the I-level of their control (leaves vacuum infiltrated with 1%
      ethanol), (iii) and in thylakoid membranes, the addition of DCMU lowers the F(M)
      relative to that of a control sample.

PMID- 15869739
TI  - A four-subunit cytochrome bc(1) complex complements the respiratory chain of
      Thermus thermophilus.
AB  - Several components of the respiratory chain of the eubacterium Thermus
      thermophilus have previously been characterized to various extent, while no
      conclusive evidence for a cytochrome bc(1) complex has been obtained. Here, we
      show that four consecutive genes encoding cytochrome bc(1) subunits are organized
      in an operon-like structure termed fbcCXFB. The four gene products are identified
      as genuine subunits of a cytochrome bc(1) complex isolated from membranes of T.
      thermophilus. While both the cytochrome b and the FeS subunit show typical
      features of canonical subunits of this respiratory complex, a further membrane
      integral component (FbcX) of so far unknown function copurifies as a subunit of
      this complex. The cytochrome c(1) carries an extensive N-terminal hydrophilic
      domain, followed by a hydrophobic, presumably membrane-embedded helical region
      and a typical heme c binding domain. This latter sequence has been expressed in
      Escherichia coli, and in vitro shown to be a kinetically competent electron donor
      to cytochrome c(552), mediating electron transfer to the ba(3) oxidase.
      Identification of this cytochrome bc(1) complex bridges the gap between the
      previously reported NADH oxidation activities and terminal oxidases, thus,
      defining all components of a minimal, mitochondrial-type electron transfer chain
      in this evolutionary ancient thermophile.

PMID- 15869740
TI  - Detergent-like properties of magainin antibiotic peptides: a 31P solid-state NMR
      spectroscopy study.
AB  - (31)P solid-state NMR spectroscopy has been used to investigate the macroscopic
      phase behavior of phospholipid bilayers in the presence of increasing amounts of
      magainin antibiotic peptides. Addition of >1 mol% magainin 2 to gel-phase DMPC or
      liquid crystalline POPC membranes respectively, results in (31)P NMR spectra that
      are characterized by the coexistence of isotropic signals and line shapes typical
      for phospholipid bilayers. The isotropic signal intensity is a function of
      temperature and peptide concentration. At peptide concentrations >4 mol% of the
      resulting phospholipid (31)P NMR spectra are characteristic of magnetically
      oriented POPC bilayers suggesting the formation of small disk-like micelles or
      perforated sheets. In contrast, addition of magainin to acidic phospholipids
      results in homogenous bilayer-type (31)P NMR spectra with reduced chemical shift
      anisotropies. The results presented are in good agreement with the interfacial
      insertion of magainin helices with an alignment parallel to the surface of the
      phospholipid bilayers. The resulting curvature strain results in detergent-like
      properties of the amphipathic helical peptides.

PMID- 15869741
TI  - Effect of deuterium oxide on the thermodynamic quantities associated with phase
      transitions of phosphatidylcholine bilayer membranes.
AB  - The bilayer phase transitions of three kinds of phospholipids,
      dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC) and
      dihexadecylphosphatidylcholine (DHPC), in deuterium oxide (D(2)O) and hydrogen
      oxide (H(2)O) were observed by differential scanning calorimetry (DSC) under
      ambient pressure and light-transmittance measurements under high pressure. The
      DSC measurements showed that the substitution of H(2)O by D(2)O affected the
      pretransition temperatures and the main-transition enthalpies of all PC bilayers.
      The temperature-pressure phase diagrams for these PC bilayer membranes in both
      solvents were constructed by use of the data of light-transmittance measurements.
      Regarding the main transition of all PC bilayer membranes, there was no
      appreciable difference between the transition temperatures in D(2)O and H(2)O
      under high pressure. On the other hand, the phase transitions among the gel
      phases including the pretransition were significantly affected by the solvent
      substitution. The thermodynamic quantities of phase transitions for the PC
      bilayer membranes were evaluated and the differences in thermodynamic properties
      by the water substitution were considered from the difference of interfacial-free
      energy per molecule in the bilayer in both solvents. It was proved that the
      substitution of H(2)O by D(2)O causes shrinkage of the molecular area of
      phospholipid at bilayer interface due to the difference in bond strength between
      deuterium and hydrogen bonds and produces the great influence on the bilayer
      phase with the smaller area. Further, the induction of bilayer interdigitation in
      D(2)O turned out to need higher pressures than in H(2)O.

PMID- 15869742
TI  - Biological and polymeric self-assembled hybrid systems: structure and properties
      of thylakoid/polyelectrolyte complexes.
AB  - A novel hybrid system composed of biological components and synthetic polymer,
      thylakoid/polycation complex, has been formed and studied. Effects of complex
      formation on the structure, electrostatics and functioning of thylakoid membranes
      have been examined. Thylakoids from bean leaves were used to form complexes with
      polycation polyallylamine hydrochloride (PAAH) in two systems: (i)
      thylakoid/polycation complexes formed in an aqueous bulk phase, and (ii)
      immobilized thylakoid/polycation planar complexes. Immobilized on a solid
      substrate surface, thylakoid/polycation complexes were prepared using layer-by
      layer stepwise alternate adsorption technique, i.e., via the sequential alternate
      adsorption of thylakoids and polycation molecules. The morphology of built up
      structures was investigated by scanning electron microscopy. Light-induced
      electron transport in chloroplasts was studied by the electron paramagnetic
      resonance (EPR) method. Spin probe technique was employed to study the structural
      and electrostatic characteristics of thylakoid membranes. We have found that
      efficiency of light-induced electron transport in thylakoid membranes and
      membrane structure were not changed noticeably by PAAH binding to thylakoids in a
      wide range of PAAH concentrations. The data obtained indicate the physiologically
      soft character of polycation interactions with thylakoid membranes and
      demonstrate effectiveness of interfacial self-assembly approach to fabrication of
      complex planar functional nanostructures from biological components and synthetic
      polymers.

PMID- 15869743
TI  - AFM characterization of solid-supported lipid multilayers prepared by spin
      coating.
AB  - Lipids are the principal components of biologically relevant structures as
      cellular membranes. They have been the subject of many studies due to their
      biological relevance and their potential applications. Different techniques, such
      as Langmuir-Blodgett and vesicle-fusion deposition, are available to deposit
      ordered lipid films on etched surfaces. Recently, a new technique of lipid film
      deposition has been proposed in which stacks of a small and well-controlled
      number of bilayers are prepared on a suitable substrate using a spin-coater. We
      studied the morphological properties of multi-layers made of cationic and neutral
      lipids (DOTAP and DOPC) and mixtures of them using dynamic mode atomic force
      microscopy (AFM). After adapting and optimizing, the spin-coating technique to
      deposit lipids on a chemically etched Silicon (1,0,0) substrate, a morphological
      nanometer-scale characterization of the aforementioned samples has been provided.
      The AFM study showed that an initial layer of ordered vesicles is formed and,
      afterward, depending on details of the spin-coating preparation protocol and to
      the dimension of the silicon substrate, vesicle fusion and structural
      rearrangements of the lipid layers may occur. The present data disclose the
      possibility to control the lipid's structures by acting on spin-coating
      parameters with promising perspectives for novel applications of lipid films.

PMID- 15869744
TI  - Chrysin induces G1 phase cell cycle arrest in C6 glioma cells through inducing
      p21Waf1/Cip1 expression: involvement of p38 mitogen-activated protein kinase.
AB  - Flavonoids are a broadly distributed class of plant pigments, universally present
      in plants. They are strong anti-oxidants that can inhibit carcinogenesis in
      rodents. Chrysin (5,7-dihydroxyflavone) is a natural and biologically active
      compound extracted from many plants, honey, and propolis. It possesses potent
      anti-inflammatory, anti-oxidant properties, promotes cell death, and perturbing
      cell cycle progression. However, the mechanism by which chrysin inhibits cancer
      cell growth remains poorly understood. Therefore, we developed an interest in the
      relationship between MAPK signaling pathways and cell growth inhibition after
      chrysin treatment in rat C6 glioma cells. Cell viability assay and flow
      cytometric analysis suggested that chrysin exhibited a dose-dependent and time
      dependent ability to block rat C6 glioma cell line cell cycle progression at the
      G1 phase. Western blotting analysis showed that the levels of Rb phosphorylation
      in C6 glioma cells exposed to 30 microM chrysin for 24h decreased significantly.
      We demonstrated the expression of cyclin-dependent kinase inhibitor,
      p21(Waf1/Cip1), to be significantly increased, but the p53 protein level did not
      change in chrysin-treated cells. Both cyclin-dependent kinase 2 (CDK2) and 4
      (CDK4) kinase activities were reduced by chrysin in a dose-dependent manner.
      Furthermore, chrysin also inhibited proteasome activity. We further showed that
      chrysin induced p38-MAPK activation, and using a specific p38-MAPK inhibitor,
      SB203580, attenuated chrysin-induced p21(Waf1/Cip1) expression. These results
      suggest that chrysin exerts its growth-inhibitory effects either through
      activating p38-MAPK leading to the accumulation of p21(Waf1/Cip1) protein or
      mediating the inhibition of proteasome activity.

PMID- 15869746
TI  - Dynamic changes in baroreceptor-sympathetic coupling during the respiratory
      cycle.
AB  - In urethane-anesthetized, paralyzed, and artificially ventilated cats, we
      observed an unusual form of "phase walk" of the cardiac-related burst of inferior
      cardiac postganglionic sympathetic nerve discharge (SND) relative to the systolic
      phase of the arterial pulse (AP) and thus pulse-synchronous baroreceptor nerve
      activity. Unlike classic phase walk ascribable to weakened coupling
      (desynchronization) of two oscillators, AP-SND phase walk was characterized by
      epochs of progressive, bidirectional changes in the angle of strong coupling (AP
      SND coherence values, >0.9) of these signals that recurred on the time scale of
      the respiratory cycle and whose range was approximately one third of the period
      of the heart beat. AP-SND phase walk was linked to two respiratory variables
      (central respiratory drive and vagal lung inflation afferent activity) as
      demonstrated by the following observations. First, in five normocapnic cats (end
      tidal CO(2), 4.3 +/- 0.2%) with intact vagus nerves and three vagotomized cats,
      AP-SND phase walk was characterized by a progressive heart-beat-to-heart-beat
      decrease in the lag of SND relative to the AP during the inspiratory phase of
      phrenic nerve activity and an increase in the lag during the expiratory phase.
      Second, in three cats with intact vagus nerves that were hyperventilated (end
      tidal CO(2), 1.6 +/- 0.4%) to phrenic nerve quiescence, the lag of the cardiac
      related burst of SND relative to the AP increased during lung inflation and
      decreased during lung deflation. Additional experimentation revealed that AP-SND
      phase walk is attributable to respiratory-induced changes in the frequency of the
      centrally generated sympathetic nerve rhythm rather than heart rate. Moreover,
      the data demonstrate that the frequency and amplitude of the sympathetic
      oscillation are independently controlled by the above mentioned respiratory
      parameters.

PMID- 15869745
TI  - Involvement of Ras/extracellular signal-regulated kinase, but not Akt pathway in
      risedronate-induced apoptosis of U937 cells and its suppression by cytochalasin
      B.
AB  - Although risedronate, a nitrogen containing bisphosphonate (BPs), strongly
      inhibits bone resorption by enhanced apoptosis of osteoclasts, its mechanism
      remained unclear. In this study, we investigated the molecular mechanism of
      risedronate-induced apoptosis of U937 cells, with a focus on extracellular signal
      regulated kinase 1/2 (ERK 1/2) and protein kinase B (Akt) pathways, mitochondria
      mediated apoptosis, and the effect of disruption of the actin cytoskeleton.
      Risedronate facilitated the relocation of Ras from membrane to cytosol through
      inhibited isoprenylation. Accordingly, risedronate suppressed the phosphorylation
      of ERK 1/2, a downstream survival signaling kinase of Ras, affected the
      intracellular distribution of Bcl-xL, and induced the mitochondrial membrane
      depolarization, cytochrome c release, activated caspase cascade and DNA
      fragmentation. The risedronate-induced apoptosis was effectively suppressed with
      cyclosporine A plus trifluoperazine, potent inhibitors of mitochondrial membrane
      permeability transition (MPT). The risedronate-induced apoptosis was independent
      of Akt, another cAMP-dependent survival signaling kinase. Risedronate facilitated
      dephosphorylation of Bad at Ser112, an ERK phosphorylation site, but not at
      Ser136, an Akt phosphorylation site. All of these apoptosis-related changes
      induced by risedronate were strongly suppressed by cytochalasin B, an inhibitor
      of actin filament polymerization. These results indicate that risedronate-induced
      apoptosis in U937 cells involves Ras/ERK, but not Akt signaling pathway, and is
      dependent on MPT, and that disruption of the actin cytoskeleton inhibits the
      risedronate-induced apoptosis at its early step.

PMID- 15869747
TI  - Brain angiotensin and anxiety-related behavior: the transgenic rat
      TGR(ASrAOGEN)680.
AB  - The transgenic rat TGR(ASrAOGEN)680, characterized by a transgene-producing
      antisense RNA against angiotensinogen in the brain, provides an opportunity to
      study the behavioral effects of angiotensin. While exposed to the elevated plus
      maze (EPM) and the light/dark box, TGR(ASrAOGEN)680 rats showed more signs of
      anxiety compared to parental Sprague-Dawley (SD) rats. In the EPM, they made
      fewer entries into the open arms, spent less time there and more time on the
      closed arms. Head dips were reduced and U-turns were increased. In the light/dark
      box, the latency to the first re-entry into the light compartment was higher in
      TGR(ASrAOGEN)680. They displayed more SAP out from the dark and a reduced number
      of transitions between the two compartments. In the social interaction test,
      active social contacts were reduced, further suggesting an anxious phenotype.
      Although there was no transgenic effect on distance traveled in the open field,
      the more anxious TGR(ASrAOGEN)680 spent less time in the inner zone. Self
      grooming was increased in TGR(ASrAOGEN)680 during exposure to the EPM and the
      open field, but was decreased in the social interaction test. In
      TGR(ASrAOGEN)680, tissue content of 5-HT and its metabolite 5-HIAA was lower in
      the hippocampus, frontal, and parietal cortex. HIAA and 5-HIAA/5-HT ratios were
      reduced in the hypothalamus, striatum, and septum. In the open field, the
      anxiogenic effect of the 5-HT2C/1B receptor agonist mCPP (0.5-1 mg/kg IP) was
      more pronounced in TGR(ASrAOGEN)680. The data suggest an anxious phenotype in
      rats with low brain angiotensinogen, possibly related to secondary dysfunctions
      of the brain serotonergic system.

PMID- 15869748
TI  - Subchronic treatment with imipramine ameliorates the decreased number in
      neuropeptide Y-positive cells in the hippocampus of learned helplessness rats.
AB  - Learned helplessness, but not immobilization stress, decreased the numbers of
      neuropeptide Y (NPY)-positive cells (interneuron), but not calcitonin gene
      related peptide (CGRP)-positive cells (mossy cell), in the hilus of the
      hippocampus. Subchronic treatment of learned helplessness rats, but not naive
      rats, with imipramine ameliorated the decrease in the number of NPY-positive
      cells. Therefore, NPY-positive cells in the hippocampus may contribute to
      depression.

PMID- 15869749
TI  - 5-hydroxytryptamine 1A (5-HT1A) but not 5-HT3 receptor is involved in mediating
      the nucleus submedius 5-HT-evoked antinociception in the rat.
AB  - Our previous studies have indicated that the thalamic nucleus submedius (Sm) is
      involved in modulation of nociception as part of an ascending component of an
      endogenous analgesic system consisting of spinal cord-Sm-ventrolateral orbital
      cortex (VLO)-periaqueductal gray (PAG)-spinal cord loop. Microinjection of 5
      hydroxytryptamine (5-HT) into Sm produces antinociception and this effect is
      blocked by 5-HT(2) receptor antagonist. The aim of the present study was to
      examine whether the 5-HT(1) and 5-HT(3) receptors were also involved in the Sm 5
      HT-evoked antinociception. Nociception was assessed in lightly anesthetized rats
      with radiant-heat-evoked tail flick (TF). 5-HT(1A) and 5-HT(3) receptor
      antagonists were microinjected into the Sm alone or in combination with a
      microinjection of 5-HT into the same Sm site. 5-HT(1A) receptor antagonist p-MPPI
      (0.87 nmol) facilitated the TF reflex; a lower dose (0.43 nmol) of p-MPPI
      significantly attenuated the Sm 5-HT-evoked inhibition of TF reflex.
      Microinjection of the 5-HT(3) receptor antagonist LY-278,584 (12 nmol) had no
      effect either on the TF reflex or on the Sm 5-HT-evoked inhibition. These results
      suggest that 5-HT(1A) receptor but not 5-HT(3) receptor is involved in mediating
      the 5-HT-evoked antinociception. Possible mechanisms of Sm 5-HT-induced
      descending antinociception are discussed.

PMID- 15869750
TI  - Alteration of kappa-opioid receptor system expression in distinct brain regions
      of a genetic model of enhanced ethanol withdrawal severity.
AB  - Abrupt withdrawal from chronic alcohol exposure can produce convulsions that are
      likely due to ethanol (EtOH) neuroadaptations. While significant efforts have
      focused on elucidating dependence mechanisms, the alterations contributing to
      EtOH withdrawal severity are less well characterized. The present studies
      examined the kappa-opioid receptor (KOP-R) system in Withdrawal Seizure-Prone
      (WSP) and Withdrawal Seizure-Resistant (WSR) mice, selected lines that display
      severe and mild convulsions upon removal from chronic EtOH exposure. Previous
      data demonstrated significant increases in whole brain prodynorphin (Pdyn) mRNA
      in WSP mice only during EtOH withdrawal. No significant effects of EtOH exposure
      or withdrawal were observed in WSR mice. The present study characterized Pdyn
      mRNA and the KOP-R in WSP and WSR mice during EtOH withdrawal using in situ
      hybridization (ISH) and KOP-R autoradiography. Analyses were performed in brain
      regions that express Pdyn mRNA and/or KOP-R and that might participate in seizure
      circuitry: the piriform cortex, olfactory tubercle, nucleus accumbens, caudate
      putamen, claustrum, dorsal endopiriform nucleus, and cingulate cortex. ISH
      analyses confirmed previous findings; EtOH withdrawal increased Pdyn mRNA in
      multiple brain regions of WSP mice, but not WSR. Basal KOP-R binding was higher
      in WSR mice than in WSP mice, suggesting an anti-convulsant role for receptor
      activation. Finally, increased KOP-R density was present during EtOH withdrawal
      in WSP mice. These data suggest that differences in the KOP-R system among the
      lines might contribute to their selected difference in EtOH withdrawal severity.

PMID- 15869751
TI  - Differential lipid packing abilities and dynamics in giant unilamellar vesicles
      composed of short-chain saturated glycerol-phospholipids, sphingomyelin and
      cholesterol.
AB  - The ability of membrane components to arrange themselves heterogeneously within
      the bilayer induces the formation of microdomains. Much work has been devoted to
      mimicking domain-assembly in artificial bilayers and characterizing their physico
      chemical properties. Ternary lipid mixtures composed of unsaturated
      phospholipids, sphingomyelin and cholesterol give rise to large, round domains.
      Here, we replaced the unsaturated phospholipid in the ternary mixture with
      sphingomyelin and cholesterol by saturated glycero-phospholipids of different
      chain length and characterized the critical role of cholesterol in sorting these
      lipids by confocal imaging and fluorescence correlation spectroscopy (FCS). More
      cholesterol is needed to obtain phase segregation in ternary mixtures, in which
      the unsaturated phospholipid is replaced by a saturated one. Finally, lipid
      dynamics in distinct phases is very low and astonishingly similar, thereby
      suggesting the poor ability of cholesterol in sorting short-chain saturated
      glycero-phospholipids and sphingomyelin.

PMID- 15869752
TI  - Elimination of high amounts of extracellular homocysteine in human cell lines.
AB  - BACKGROUND: Many clinical and epidemiological studies show that mild
      hyperhomocysteinemia is associated with premature vascular disease. Information
      about the metabolism of homocysteine is therefore essential for an understanding
      of its role in atherogenesis, thereby enabling a modulation of that risk.
      METHODS: In the present study factors influencing the elimination of exogenously
      added homocysteine in HeLa and hepatoma cell cultures have been investigated with
      and without inhibition of the transmethylation pathway by adenosine-dialdehyde.
      RESULTS: Agents with antioxidative effect (copper chelator and thiols) increased
      the metabolic removal of extracellular homocysteine in HeLa cell cultures,
      whereas in hepatoma cell cultures only the thiol N-acetylcysteine increased the
      elimination. The oxidative agent (copper ions) and cyst(e)ine transport
      inhibitors decreased the removal in both HeLa and hepatoma cell cultures. The
      inhibition of the transmethylation pathway by adenosine-dialdehyde increased the
      removal of exogenously added homocysteine and the addition of the different redox
      agents and cyst(e)ine transport inhibitors did not specifically influence this
      increase. CONCLUSION: The elevated removal of exogenously added homocysteine in
      the presence of adenosine-dialdehyde might be attributed to limited availability
      of intracellular homocysteine, which leads to a larger amount of extracellular
      homocysteine being internalized.

PMID- 15869753
TI  - Combined effect of probucol and insulin on cataracts of diabetic rats fed a high
      cholesterol diet.
AB  - We investigated the effects of long-term treatment with probucol, a hypolipidemic
      agent with antioxidative action, insulin, or their combination on cataracts of
      streptozotocin-induced diabetic rats fed a high cholesterol diet. Each rat was
      checked for cataracts at 0, 1, 2, 4, 8, 12 and 15 weeks after streptozotocin
      injection. Cataracts were observed from 8 weeks in untreated hypercholesterolemic
      and diabetic rats and the incidence of catarats increased to 100% by 15 weeks.
      The incidence of cataracts in rats treated with probucol, insulin and their
      combination was first seen at 12, 12 and 15 weeks, respectively, and was 86%, 63%
      and 33%, respectively, at 15 weeks. The preventive effects of both agents alone
      and their combination on the cataracts were confirmed by histopathological
      evaluation of eyeballs. The combined treatment with both agents markedly improved
      hyperglycemia, hyperlipidemia and increased serum lipid peroxide levels. These
      results indicate that the combined treatment with probucol and insulin is useful
      in preventing the development and progression of diabetic cataracts.

PMID- 15869754
TI  - Altered posttranslational processing of glycoproteins in cerulein-induced
      pancreatitis.
AB  - Acute pancreatitis is an auto-digestive disease resulting in inflammation. At the
      cellular level, acute pancreatitis disrupts posttranslational protein processing
      and traffic in the secretory pathway, and zymogens become activated in the acinar
      cell. To better understand the disruption of the secretory pathway in
      pancreatitis, pulse-chase [(35)S]met/cys analysis was used to study the effects
      of supramaximal cerulein stimulation on posttranslational modification in the
      secretory pathway of the major sulfated glycoprotein of the mouse pancreas, pro
      Muclin, and the lysosomal membrane protein LAMP1. Maximal cerulein or high
      concentration bombesin stimulation had little effect on glycoprotein processing.
      By contrast, supramaximal cerulein stimulation strongly inhibited pro-Muclin
      processing as measured by the failure of Muclin to attain its normal mature size
      of 300 kDa and to become highly sulfated and decreased proteolytic cleavage of
      pro-Muclin to produce apactin. Digestion of immunoprecipitated [35S]met/cys
      labeled Muclin and LAMP1 with endoglycosidase H demonstrated that the
      supramaximal cerulein-induced block in processing occurred before the medial
      Golgi compartment. With supramaximal cerulein stimulation, vacuoles formed which
      contained Muclin, amylase, and LAMP1. Earlier autoradiographic studies showed
      that newly synthesized proteins end up in pancreatitis-associated vacuoles, so it
      is likely that glycoproteins with incomplete posttranslational processing are
      also present in vacuoles. Because glycoproteins are believed to protect the
      membranes of lysosomes and zymogen granules, when they are not correctly
      processed, their defensive mechanisms may be impaired, and this could contribute
      to vacuole fragility in pancreatitis.

PMID- 15869755
TI  - Entamoeba histolytica: molecular characterization of an aldose 1-epimerase
      (mutarotase).
AB  - In cells, the alpha-anomers of aldoses are the preferred metabolizable
      substrates, while beta-anomers of aldoses play their role in glycan structure. In
      the cytoplasm, alpha- and beta-anomers of aldoses interconvert through the enzyme
      termed aldose 1-epimerase or mutarotase (EC 5.1.3.3). We have identified a
      mutarotase gene in Entamoeba histolytica, the causative agent of non-bacterial
      dysentery in humans. Cloning and characterization of this gene in two strains of
      the parasite (HM-1:IMSS and Rahman) that differ in their pathogenicity, revealed
      that the sequence is identical in both strains. A recombinant E. histolytica
      mutarotase was produced as well as specific antibodies that recognized a 38 kDa
      protein in trophozoite lysates of both strains. Mutarotase activity was observed
      with the recombinant protein as well as in lysates of both HM-1:IMSS and Rahman,
      the former exhibiting a slightly higher mutarotase activity. Finally, we have
      shown by complementation that overexpression of the E. histolytica mutarotase in
      a mutarotase defective Escherichia coli strain restores the ability of these
      bacteria to grow in minimal medium with phenyl-beta-galactopyranoside as the sole
      carbon source.

PMID- 15869756
TI  - Babesia caballi and Babesia equi: implications of host sialic acids in
      erythrocyte infection.
AB  - The present study investigated the involvement of host sialic acids in the
      erythrocyte infection by two equine Babesia parasites, Babesia equi and Babesia
      caballi. We observed that the in vitro growth of both parasites is influenced by
      the removal of sialic acids from the surface of equine erythrocytes (RBC). When
      the parasites were cultured with neuraminidase (Nm, EC 3.2.1.18)-treated RBC, in
      which alpha2-3-linked sialic acid residues were removed from four membrane
      proteins of the RBC, B. caballi showed a significant inhibition of the
      erythrocyte invasion, while the intracellular development of B. equi seemed to be
      significantly affected. The possible involvement of host sialic acid in the
      erythrocyte invasion by B. caballi was also supported by a significant reduction
      in the parasite growth accompanied by an increased number of extracellular
      merozoites after the addition of exogenous 3'-sialyllactose (Neu5Acalpha(2
      3)Galbeta(1-4)Glc) into the culture. These results suggest that the alpha2-3
      linked sialic acid residues on host RBC play important roles in the erythrocyte
      infections by B. caballi and B. equi.

PMID- 15869757
TI  - Reactive molecules and microorganisms and copper intrauterine devices.

PMID- 15869758
TI  - Metabolic syndrome in aboriginal Canadians: prevalence and genetic associations.
AB  - OBJECTIVES: The prevalence rates of type 2 diabetes (T2DM) and coronary heart
      disease (CHD) in Ontario Oji-Cree are among the world's highest. Since metabolic
      syndrome (MetS) increases risk of T2DM and CHD, we characterized prevalence and
      putative genetic determinants of MetS in Oji-Cree. METHODS AND RESULTS: In 515
      adult (> or = 18 years old) and 115 adolescent (< 18 years old) Oji-Cree
      subjects, using the National Cholesterol Education Program Adult Treatment Panel
      III (NCEP ATP III) criteria, we determined that 29.9% of Oji-Cree adults, and
      43.4% of adults > or = 35 years of age, had MetS. Furthermore, 33.9 and 8.7% of
      female Oji-Cree adults and adolescents, respectively, had MetS. Increased waist
      girth and depressed HDL cholesterol were the most prevalent individual MetS
      components, while increased blood pressure was least prevalent. AGT T174M, GNB3
      825C>T, and APOC3 -455T>C genotypes were significantly associated with MetS (P =
      0.018, 0.0056, and 0.029, respectively) for female adults, whereas FABP2 A54T
      genotype was associated with MetS (P = 0.040) for female adolescents.
      CONCLUSIONS: The high MetS prevalence in Oji-Cree adults, especially women, is
      consistent with their high risk of T2DM and CHD. Functional polymorphisms in
      three candidate genes for plasma lipoproteins and blood pressure were associated
      with MetS in adult Oji-Cree. Furthermore, several female adolescents met the
      adult MetS criteria, suggesting that the genesis of MetS begins in youth,
      especially among aboriginal females.

PMID- 15869759
TI  - Vibration training: benefits and risks.
AB  - The main results of our recent several studies, i.e. the measurements of
      vibration training results for single case and group studies as well as the
      cardiovascular parameter measurements during vibrations and the corresponding
      hydrodynamic analysis, are summarized. Our studies and previous work all confirm
      that vibration training is an effective training method in order to improve
      maximal strength and flexibility as well as various other factors if the training
      is properly designed. Some recommendations regarding the proper ranges of
      frequencies, amplitudes and exposure duration of vibration training are made
      based on the existing vibration training practice and mechanism analysis,
      although much work remains to be carried out in order to set up clear rules for
      various groups of people so that maximal training results could be expected and
      in the meantime potential dangerous effects could be avoided. Cardiovascular
      parameter measurements confirm that total peripheral resistance (TPR) to the
      blood flow is increased during body vibration. Hydrodynamic analysis offers the
      mechanism for the increase of TPR through the deformation of vessels. As a
      reaction of compensation, more capillaries are probably opened in order to keep a
      necessary level of cardiac output needed for the body, resulting in more
      efficient gas and material metabolism between the blood and muscle fibres. This
      might be one of the reasons for the various potential beneficial effects of
      vibration training.

PMID- 15869760
TI  - A secret agent? How infants learn about the identity of objects in a causal
      scene.
AB  - Four experiments examined the role of correlations between dynamic and static
      parts on 12- to 16-month-olds' ability to learn the identity of agents and
      recipients in a simple causal event. Infants were habituated to events in which
      objects with a dynamic or static part acted as an agent or a recipient and then
      were tested with an event in which the part-causal role relations were switched.
      Experiment 1 revealed that 16-month-olds, but not 12-month-olds, associate a
      dynamic part with the role of agent and a static part with the role of recipient.
      Experiment 2 showed that 12- and 16-month-olds do not associate a static part
      with the role of agent or a dynamic part with the role of recipient. Experiment 3
      demonstrated that 14-month-olds will learn the relations presented in Experiment
      1 and Experiment 2. Experiment 4 revealed that 12-month-olds were able to
      discriminate the two geometric figures in the events. The results are discussed
      with respect to infants' developing ability to attend to correlations between
      dynamic and static cues and the mechanism underlying early object concept
      acquisition.

PMID- 15869761
TI  - Molecular characterization and expression of prothoracicotropic hormone during
      development and pupal diapause in the cotton bollworm, Helicoverpa armigera.
AB  - Using a strategy of rapid amplification of cDNA ends, the cDNA encoding
      prothoracicotropic hormone (PTTH) was cloned from the brain of Helicoverpa
      armigera (Hearm). The Hearm-PTTH cDNA contains an open reading frame encoding a
      226-amino acid preprohormone, which shows high identity with the closely related
      noctuid moths, Helicoverpa zea (98%) and Heliothis virescens (94%), and low
      identity with five species of Bombycoidea: Bombyx mori (57%), Manduca sexta
      (55%), Hyalophora cecropia (52%), Samia cynthia ricini (49%) and Antheraea peryni
      (48%). Hearm-PTTH cDNA shares important structural characterization known from
      other PTTHs, such as seven cysteine residues, proteolytic cleavage site,
      glycosylation site, and hydrophobic regions within the mature peptides. Northern
      blot analysis indicated a 0.9kb transcript present only in the brain. Using the
      more sensitive technique of RT-PCR, PTTH mRNA was also detected in the
      subesophageal ganglion, thoracic ganglion, abdominal ganglion, midgut and fat
      body. During the pupal stage, PTTH mRNA in the brain remained at a constant high
      level in nondiapausing individuals, was low in diapausing pupae, but increased
      again at diapause termination. The PTTH protein was detected only in the brain by
      Western blot analysis. Immunocytochemical results revealed that Hearm-PTTH is
      localized in two pairs of dorsolateral neurosecretory cells within the brain.
      Recombinant Hearm-PTTH was successfully expressed in E. coli, and purified
      recombinant-PTTH was effective in breaking pupal diapause. The results are
      consistent with a role for PTTH in the regulation of diapause in this species.

PMID- 15869762
TI  - The effect of an angiotensin converting enzyme inhibitor on intestinal wound
      healing.
AB  - BACKGROUND: Dehiscence of intestinal anastomosis is associated with high
      mortality and morbidity rates. Angiotensin II is a potent agent in the
      acceleration of wound repair. Angiotensin converting enzyme (ACE) inhibitors have
      antifibrogenic effects. AIM: This study was performed to investigate the effect
      of ACE inhibitors on healing of intestinal anastomosis. MATERIALS AND METHODS:
      Forty-five male Wistar albino rats were divided into three groups. Ileum was
      divided above 10 cm from ileocecal valve after laparotomy and a single-layer
      ileoileal anastomosis was performed. While no treatment was given to rats in
      group 1, Lisinopril (an ACE inhibitor) was given to rats in group 2 and group 3
      for post-operative 7 days in drinking water at 50 and 5 mg/l concentrations,
      respectively. Estimated amounts of supplied lisinopril were 6.5 and 0.65
      mg/kg/day in groups. On post-operative 8th day, relaparotomy was performed and
      anastomosis-bursting pressures were measured. Then blood and tissue samples were
      taken for serum transforming growth factor beta-1 and tissue hydroxyproline
      measurements and histopathological examinations. RESULTS: High dose of lisinopril
      impaired the all parameters of anastomotic wound healing including bursting
      pressure, tissue hydoxyproline level, collagen deposition and epithelization (P <
      0.001, group 2 versus groups 1 and 3). But low dose of lisinopril had no effect
      on those parameters (P > 0.05, group 1 versus group 3). CONCLUSION: It was
      concluded that lisinopril has impaired intestinal wound healing in a dose
      dependent manner and low doses of lisinopril can be safely used on patients with
      intestinal anastomosis.

PMID- 15869763
TI  - Plasmin induces smooth muscle cell proliferation.
AB  - BACKGROUND: Plasminogen activators are routinely used for thrombolysis. They lead
      to the generation of the protease, plasmin, which can induce smooth muscle cell
      proliferation and may thus promote further intimal hyperplasia in the
      thrombolysed vessel. The signaling pathways used by plasmin are not understood.
      METHODS: Murine aortic smooth muscle cells were cultured in vitro. Assays of DNA
      synthesis, cell proliferation, MAPKK and MAPK activation were examined in
      response to plasmin alone and in the presence of plasmin inhibitors (epsilon
      aminocaproic acid and aprotinin), pertussis toxin (Galphai inhibitor, PTx), GP-2A
      (Galphaq inhibitor), wortmannin (PI3-K inhibitor, Wn), LY294002, (PI3-K
      inhibitor, LY), PD98059 (MEK inhibitor, PD), and SB203580 (p38MAPK inhibitor,
      SB). RESULTS: Plasmin produced concentration dependent smooth muscle cells DNA
      synthesis and proliferation and induced ERK1/2 and p38MAPK phosphorylation.
      Inhibition of the proteolytic activity of plasmin prevented these responses. The
      ERK1/2 inhibitor, PD, but not the p38MAPK inhibitors, SB, blocked cell
      proliferation. The activation of the MEK1/2 and ERK1/2 pathway was both Galphai
      dependent (PTx-sensitive) and Galphaq dependent (GP-2A-sensitive). It was blocked
      by the PI3-K inhibitors, Wn and LY. PI3-K activation as measured by akt
      phosphorylation was dependent on Galphai, but was independent of Galphaq.
      CONCLUSION: Plasmin induces smooth muscle cell proliferation. Plasmin induced
      ERK1/2 phosphorylation occurs through two pathways: one which is Galphai
      mediated/PI3-K dependent and a second which is Galphaq mediated/PI3K independent.
      p38MAPK appears not to be involved in plasmin-mediated cell proliferation. This
      pattern of activation is distinct from that seen with urokinase plasminogen
      activator.

PMID- 15869764
TI  - Angiotensin converting enzyme-independent angiotensin ii production by chymase is
      up-regulated in the ischemic kidney in renovascular hypertension.
AB  - BACKGROUND: Tissue angiotensin II (ANG II) levels are elevated in both kidneys in
      renovascular hypertension (RVH). It has been demonstrated previously that
      intrarenal ANG II is augmented by an angiotensin converting enzyme (ACE)
      dependent mechanism in the non-ischemic kidney, but the role of ACE-independent
      production of ANG II in the kidney by the enzyme chymase is unknown. This study
      tested the hypothesis that intrarenal chymase activity is up-regulated in RVH.
      METHODS: A two-kidney, one-clip (2K1C) rat model was used to induce RVH (n = 6
      rats/group). Regulation of intrarenal chymase activity by plasma ANG II was
      investigated using an ANG II-infusion model. At sacrifice 14 days post
      operatively, steady-state ANG II levels in plasma and kidney were quantified by
      radioimmunoassay. ANG II production was quantified in kidney homogenates by
      incubating at 37 degrees C for 60 min with enzyme substrate (200 microm ANG I)
      alone or substrate containing the chymase inhibitor chymostatin. ANG II was
      separated and quantitated by HPLC. Chymase activity was defined as the fraction
      of ANG II production inhibited by Chymostatin. RESULTS: 2K1C and ANG II-infused
      rats developed significant hypertension, compared to control rats (P = 0.0001 and
      P = 0.001, respectively). Chymase-dependent ANG II production was increased in
      the ischemic kidney, but not the non-ischemic kidney, of 2K1C rats compared to
      control animals (*P < 0.05). Intrarenal chymase activity was unchanged by ANG II
      infusion (P = NS). CONCLUSIONS: Chymase activity is up-regulated in the ischemic
      kidney of 2K1C rats. Plasma ANG II does not appear to regulate intrarenal chymase
      activity, suggesting that ischemia per se up-regulates chymase activity in the
      kidney. ACE-independent ANG II production by chymase may provide a mechanism for
      augmenting intrarenal ANG II in the ischemic kidney in RVH.

PMID- 15869765
TI  - Secretion of brain-derived neurotrophic factor by glatiramer acetate-reactive T
      helper cell lines: Implications for multiple sclerosis therapy.
AB  - Treatment with glatiramer acetate (GA) is thought to induce an in vivo change of
      the cytokine secretion pattern and the effector function of GA-reactive T helper
      (TH) cells (TH1-TH2-shift). Current theories propose that GA-reactive TH2 cells
      can penetrate the CNS, since they are activated by daily immunization. Inside the
      CNS, GA-reactive T cells may cross-react with products of the local myelin
      turnover presented by local antigen-presenting cells (APCs). Thus, some of the GA
      specific TH2 cells may be stimulated to release anti-inflammatory cytokines
      inhibiting neighbouring inflammatory cells by a mechanism called bystander
      suppression. We demonstrate that both GA-specific TH2 and TH1 cells produce the
      neurotrophin brain-derived neurotrophic factor (BDNF). To demonstrate that GA
      reactive T cells produce BDNF, we analyzed GA-specific, long-term T-cell lines
      (TCLs) and used a combination of reverse-transcription PCR and two specially
      designed techniques for BDNF protein detection: one was based on ELISA of
      supernatants from co-cultures of GA-specific TCLs plus GA-pulsed antigen
      presenting cells, and the other, on the direct intracellular staining of BDNF in
      individual T cells and flow-cytometric analysis. The different assays and
      different TCLs yielded similar, consistent results. All GA-specific TH1, TH2 and
      TH0 lines could be stimulated to produce BDNF.

PMID- 15869766
TI  - Auditory perceptual consolidation in early-onset blindness.
AB  - Early-onset blindness (EB) produces measurable advantages in auditory perception,
      attention, memory and language. Neville and Bavelier [Neville, H. J., & Bavelier,
      D. (2001) Variability of developmental plasticity. In J. L. McClelland, R. S.
      Siegler (Eds.) Mechanisms of cognitive development: Behavioral andellon symposia
      on cognition (pp. 271-301)] hypothesized that faster temporal processing
      underlies many auditory compensatory effects in the blind. We tested this
      hypothesis by comparing early-onset blind individuals and sighted counterparts
      (SC) by assessing their rates of perceptual consolidation, the accurate
      perceptual representation of auditory stimuli. Firstly, we first tested both
      groups on a temporal-order judgment task (TOJ). EB subjects had significantly
      lower TOJ thresholds than the SC subjects. Secondly, we assessed perceptual
      consolidation speed using auditory backward masking tasks, taking into account
      individual TOJ thresholds. Discrimination performance was unaffected at all mask
      delays in the EB group while the SC subjects needed a mask delay of 160 ms to
      perform comparably. A backward masking task using single tone stimuli found no
      differences between the EB and SC groups any mask delay. A simultaneous masking
      task demonstrated that the mask effectively impaired discrimination in EB
      subjects at sensory stages. These results suggest that advantages in perceptual
      consolidation may reflect a mechanism responsible for the short response times
      and better performance reported in early blind individuals across a number of
      complex auditory tasks.

PMID- 15869767
TI  - Rainbow trout can discriminate between feeds with different oil sources.
AB  - The purpose of present two-choice trials was to examine the capacity of groups of
      juvenile rainbow trout to differentiate between two isolipidic diets containing
      distinct oils and to detect an eventual preference. The choice was offered by
      means of two self-feeders per tank. One feeder distributed a standard diet with
      fish oil (FO), the other a diet containing vegetable oil, either rich in
      linolenic acid (linseed oil, LO), linoleic acid (sunflower oil, SO), or oleic
      acid (rapeseed oil, RO). Each 15-day preference test was preceded by a 15-day
      adaptation period during which both feeders distributed the same diet. The tests
      were followed by a 10- to 15-day validation period in order to confirm that
      feeder solicitations were steered by the characteristics of the diets.
      Preferences were expressed as relative changes in feed demands for a specific
      feeder. Averaged over all groups, the preference tests demonstrated the capacity
      of rainbow trout to discriminate between a diet with FO and a diet containing
      vegetable oil, and indicated a general preference for the diet with FO over the
      other diets irrespective of whether they received the diet with fish oil
      (Experiment 1) or with vegetable oil (Experiment 2) prior to the preference test.
      The tests also indicated a difference in the extent of relative avoidance of each
      of the three vegetable oil diets. Diet LO was the most avoided, as indicated by
      the 37-39% decrease in demands for the feeder with diet LO (P<0.05). Diet RO was
      the best accepted, causing a decrease in feed demands of only 15-17% (P>0.05).
      The avoidance of diet SO at the end of the preference test was 30% (P>0.05) after
      an initially higher avoidance of 43% (P<0.05). It is believed that the metabolic
      consequences of the excess of linolenic or linoleic acid negatively affected the
      feed acceptances of diets LO and SO. Further work is needed to elucidate a
      possible interference of differences in palatability. In all groups, the lower
      demands for the vegetable oil diets were compensated by increased demands for
      diet FO. Hence, changes in diet selection had no effect on total feed or energy
      intakes, measured as the sum of both selections.

PMID- 15869769
TI  - Sex-specific effects of corticosterone on hippocampally mediated learning in
      young rats.
AB  - Glucocorticoids administered during development can have lasting consequences on
      learning performance and brain development. Whereas most studies administer
      glucocorticoids to the young rat during the so-called stress-hyporesponsiveness
      period (SHRP), we examined the effects of corticosterone pellets implanted at the
      conclusion of the SHRP on two forms of eye blink conditioning (EBC). Analysis of
      blood samples indicated that pellets implanted on Day 15 released the bulk of the
      corticosterone before Day 21. In tests of EBC beginning on Day 28, corticosterone
      treated males, but not females, showed impaired performance in the hippocampally
      mediated "trace" version of the EBC paradigm. There were no effects of
      corticosterone on the "delay" version of the task. These results are consistent
      with earlier findings that the hippocampus is particularly sensitive to elevated
      glucocorticoid levels. Moreover, the findings suggest that glucocorticoids
      administered after the SHRP may produce subtle effects on learning performance
      akin to those that have been reported in children.

PMID- 15869768
TI  - Serotonin alterations in anorexia and bulimia nervosa: new insights from imaging
      studies.
AB  - Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders with
      relatively homogenous presentations such as age of onset and gender distribution.
      In addition, they share symptoms, such as extremes of food consumption, body
      image distortion, anxiety and obsessions, and ego-syntonic neglect, raises the
      possibility that these symptoms reflect disturbed brain function that contributes
      to the pathophysiology of this illness. Recent brain imaging studies have
      identified altered activity in frontal, cingulate, temporal, and parietal
      cortical regions in AN and BN. Importantly, such disturbances are present when
      subjects are ill and persist after recovery, suggesting that these may be traits
      that are independent of the state of the illness. Emerging data point to a
      dysregulation of serotonin pathways in cortical and limbic structures that may be
      related to anxiety, behavioral inhibition, and body image distortions. In
      specific, recent studies using PET with serotonin specific radioligands implicate
      alterations of 5-HT1A and 5-HT2A receptors and the 5-HT transporter. Alterations
      of these circuits may affect mood and impulse control as well as the motivating
      and hedonic aspects of feeding behavior. Such imaging studies may offer insights
      into new pharmacology and psychotherapy approaches.

PMID- 15869770
TI  - Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and
      efficacy of the artesunate plus sulfadoxine-pyrimethamine and artesunate plus
      amodiaquine combinations.
AB  - Both northern and southern Sudan are deploying artemisinin-based combinations
      against uncomplicated Plasmodium falciparum malaria (artesunate+sulfadoxine
      pyrimethamine [AS+SP] in the north, artesunate+amodiaquine [AS+AQ] in the south).
      In 2003, we tested the efficacy of 3 day AS+SP and AS+AQ regimens in vivo in the
      isolated, seasonally endemic Nuba Mountains region (the first study of AS
      combinations in southern Sudan). We also analysed pre-treatment blood samples for
      mutations at the P. falciparum chloroquine transporter (Pfcrt) gene (associated
      with CQ resistance), and at the dihydrofolate reductase (Dhfr) gene (associated
      with pyrimethamine resistance). Among 161 randomized children under 5 years, PCR
      corrected cure rates after 28 days were 91.2% (52/57, 95% CI 80.7-97.1) for AS+SP
      and 92.7% (51/55, 95% CI 82.4-98.0) for AS+AQ, with equally rapid parasite and
      fever clearance. The Pfcrt K76T mutation occurred in 90.0% (144/160) of
      infections, suggesting CQ would work poorly in this region. Overall, 82.5%
      (132/160) carried mutations at Dhfr (N51I, C59R or S108N, but not I164L), but
      triple mutants (more predictive of in vivo SP failure) were rare (3.1%). CQ use
      should be rapidly discontinued in this region. SP resistance may propagate
      rapidly, and AS+AQ is likely to be a better long-term option, provided AQ use is
      limited to the combination.

PMID- 15869771
TI  - The effect of eight half-yearly single-dose treatments with DEC on Wuchereria
      bancrofti circulating antigenaemia.
AB  - The effect of eight half-yearly treatment rounds with diethylcarbamazine (DEC;
      6mg/kg bodyweight) on Wuchereria bancrofti-specific circulating filarial antigen
      (CFA), a marker of adult worm infection, was followed in 79 individuals who were
      CFA-positive before start of treatment. Half of these were also microfilariae
      (mf)-positive. Microfilaraemia decreased rapidly after onset of treatment and
      became undetectable after four treatments. Circulating antigenaemia also
      decreased progressively, but at a much slower rate. After two, four and eight
      treatment rounds, the mean CFA intensity was reduced by 81, 94 and 98%, and the
      prevalence of CFA positivity was 85, 66 and 57%, compared with pre-treatment,
      respectively. CFA clearance rates were negatively related to pre-treatment CFA
      intensities, and were higher among pre-treatment mf-negative individuals than
      among pre-treatment mf-positive individuals. Even among patients who had pre
      treatment CFA intensities above the upper measuring level (32000antigen units),
      and who continued to have intensities above this level after treatment, a
      decrease in post-treatment CFA intensities was obvious from a continuous decrease
      in ELISA optical density values. Repeated DEC therapy thus appears to have a slow
      but profound and persistent macrofilaricidal effect, which in the long run may be
      beneficial to populations undergoing DEC-based control interventions by reducing
      the probability of future morbidity development.

PMID- 15869772
TI  - Identification of three members of the Anopheles funestus (Diptera: Culicidae)
      group and their role in malaria transmission in two ecological zones in Nigeria.
AB  - The role of the Anopheles funestus group in malaria transmission was investigated
      in two ecological zones in Nigeria. Sampling was carried out at four sites each
      around Ibadan (forest) and Ilorin (savanna). Human landing catches were
      supplemented with indoor and outdoor resting collections. PCR was used to
      identify 1848 A. funestus group mosquitoes to species level (749 in the savanna,
      1099 in the forest) and three species were identified. In the forest, A. funestus
      s.s. predominated (55.4%), followed by A. rivulorum (27.6%) and A. leesoni
      (17.0%). Anopheles funestus was found mostly indoors. Anopheles rivulorum and A.
      leesoni predominated in outdoor collections (P<0.001). Only Anopheles funestus
      s.s. was found in the savanna. ELISA analysis of 803 blood meal-positive
      specimens showed that over half of the blood meals were taken from humans in both
      ecotypes. The human blood index in A. funestus from the two study areas was
      similar. Anopheles funestus s.s. was the only species found positive for
      Plasmodium falciparum using ELISA, with overall infection rates of 2.3% and 1.0%
      in the forest and savanna respectively. The presence of three A. funestus species
      in Nigeria emphasizes the desirability of correct species identification within a
      malaria vector control programme.

PMID- 15869773
TI  - Risk factors for infection by the Entamoeba histolytica/E. dispar complex: an
      epidemiological study conducted in outpatient clinics in the city of Manaus,
      Amazon Region, Brazil.
AB  - An epidemiological study was conducted on a population attending outpatient
      clinics in Manaus, Amazon, Brazil to determine the prevalences of infection by
      the Entamoeba histolytica/E. dispar complex and by E. histolytica alone, as well
      as to identify the risk factors involved in transmission. The study was conducted
      in two phases: survey and case-control. Face-to-face interviews were carried out
      and faecal samples collected from 1578 individuals. Faeces were examined by
      optical microscopy and tested for the pathogenic E. histolytica specific antigen.
      Positivity to E. histolytica/E. dispar was 21.5% (340 cases). Cases were compared
      with 340 control samples, negative for the E. histolytica/E. dispar complex based
      on examination by optical microscopy. The analysis was conducted by logistic
      regression. The risk factors identified were: place of residence, age, ingestion
      of raw vegetables, quality of water consumed, number of rooms and bedrooms per
      house, and having other protozoan infections. Specific antigen detection tests
      identified 22 participants infected by E. histolytica (6.8%) among those positive
      for E. histolytica/E. dispar. There was a higher proportion of males among
      participants infected by E. histolytica than among those with E. dispar
      infections. The study population was asymptomatic or presented non-specific
      symptoms that could be attributed to amoebiasis.

PMID- 15869774
TI  - Chagas disease control: deltamethrin-treated collars reduce Triatoma infestans
      feeding success on dogs.
AB  - Dogs are domestic reservoir hosts of Trypanosoma cruzi, the aetiological agent of
      Chagas disease. Using an experimental set-up mimicking rural mud-and-thatch
      houses, we evaluated the effect of deltamethrin-treated dog collars on the
      feeding success and survival of Triatoma infestans, the main T. cruzi vector in
      Latin America. Seven collared and three uncollared control dogs were exposed to
      colonized T. infestans at day 0 (i.e. before attachment of collars), at 15 days,
      and then monthly for 3 months post collar attachment. Following overnight
      exposure to uncollared dogs, 96% (1473/1538) of bugs fed, of which 51% (746/1473)
      fully engorged. Feeding rates were significantly reduced on collared dogs for up
      to 1 month post collar attachment with the lowest rates of 91% (551/604) observed
      at day 30 (P<0.05). Amongst those bugs that fed, engorgement rates were
      significantly reduced on collared dogs throughout the trial, during which average
      rates were 31% (543/1768) (P<0.001). No collar effect on individual bug survival
      was observed. Although observed effects on feeding and engorgement were limited,
      the strong association between blood-feeding, blood meal size and T. cruzi
      transmission suggests that deltamethrin-treated dog collars could help to control
      canine (and possibly human) T. cruzi infection.

PMID- 15869775
TI  - Anthroponotic cutaneous leishmaniasis in Tunisia: presence of Leishmania killicki
      outside its original focus of Tataouine.
AB  - The first three documented cases of anthroponotic cutaneous leishmaniasis due to
      Leishmania killicki are reported from locations outside the original focus of
      Tataouine in southeast Tunisia. Three strains were isolated from three patients
      from Gafsa, Sidi Bouzid and Seliana indicating an extension of this parasite's
      range towards the centre and the north of Tunisia.

PMID- 15869776
TI  - Positive control wells: a potential answer to remote-area quality assurance of
      malaria rapid diagnostic tests.
AB  - Malaria rapid diagnostic tests (RDTs) are a potential breakthrough in the
      provision of accurate diagnosis in remote areas, but widescale use is hampered by
      uncertainty over accuracy under field conditions. Positive control wells, which
      contain recombinant malaria parasite antigen, are a novel method for addressing
      this need for quality assurance. The potential of a commercially available
      positive control well, reconstituted with blood, was assessed for use in routine
      monitoring of RDT sensitivity in a remote malaria-endemic region. When maintained
      at 4 degrees C, the wells produced a consistent level of parasite lactate
      dehydrogenase (pLDH) antigen activity, as detected by pLDH-detecting RDTs, but
      activity reduced after cumulative exposure to temperatures likely to be
      encountered over a few months in a malaria-endemic area. This limitation was
      successfully overcome in the field through centralized, controlled storage.
      Monitoring of RDT sensitivity was successfully incorporated into routine
      supervisory visits to remote clinics. However, improved temperature stability of
      the wells would enhance their potential. The threshold at which the wells' signal
      reduced RDT sensitivity requires further investigation. The wells show potential
      to overcome an important obstacle to the wide implementation of accurate parasite
      based diagnosis and appropriate treatment. Further assessment of their place in
      malaria management is warranted.

PMID- 15869777
TI  - An exotic sinusitis.
AB  - We report a case of sinusitis caused by mixed free-living amoebae, Acanthamoeba
      and Naegleria, in an immunocompetent host; this has not been documented before.
      Free-living amoebae should be considered in the differential diagnosis of
      pathogens that cause sinusitis with or without central nervous system
      involvement, especially when bacteria or fungi are not found by smear, biopsy or
      culture.

PMID- 15869778
TI  - Pipeline materials modify the effectiveness of disinfectants in drinking water
      distribution systems.
AB  - We studied how pipe material can modify the effectiveness of UV- and chlorine
      disinfection in drinking water and biofilms. This study was done with two pipe
      materials: copper and composite plastic (polyethylene, PE) in a pilot scale water
      distribution network. UV-disinfection decreased viable bacterial numbers in the
      pilot waterworks and outlet water of pipes on average by 79%, but in biofilms its
      disinfecting effect was minor. Chlorine decreased effectively the microbial
      numbers in water and biofilms of PE pipes. In outlet water from copper pipes, the
      effect of chlorination was weaker; microbial numbers increased back to the level
      before chlorination within a few days. In the biofilms present in the copper
      pipes, chlorine decreased microbial numbers only in front of the pipeline. One
      reason for weaker efficiency of chlorine in copper pipes was that its
      concentration declined more rapidly in the copper pipes than in the PE pipes.
      These results means that copper pipes may require a higher chlorine dosage than
      plastic pipes to achieve effective disinfection of the pipes.

PMID- 15869779
TI  - Riverbank filtration for control of microorganisms: results from field
      monitoring.
AB  - Microbial monitoring was conducted over a period of more than 1 year at three
      full-scale riverbank filtration (RBF) facilities, located in the United States
      along the Ohio, Missouri, and Wabash Rivers. Results of this study demonstrated
      the potential for RBF to provide substantial reductions in microorganism
      concentrations relative to the raw water sources. Cryptosporidium and Giardia
      were detected occasionally in the river waters but never in any of the well
      waters. Average concentrations and log reductions of Cryptosporidium and Giardia
      could not be accurately determined due to the low and variable concentrations in
      the river waters and the lack of detectable concentrations in the well waters.
      Average concentrations of aerobic and anaerobic spore-forming bacteria, which
      have both been proposed as potential surrogates for the protozoans, were reduced
      at the three facilities by 0.8 to > 3.1 logs and 0.4 to > 4.9 logs, respectively.
      Average concentrations of male-specific and somatic bacteriophage were reduced by
      > 2.1 logs and 3.2 logs, respectively. Total coliforms were rarely detected in
      the well waters, with 5.5 and 6.1 log reductions in average concentrations at the
      two wells at one of the sites relative to the river water. Average turbidity
      reductions upon RBF at the three sites were between 2.2 and 3.3 logs. Turbidity
      and microbial concentrations in the river waters generally tracked the river
      discharge; a similar relationship between the well water concentrations and river
      discharge was not observed, due to the low, relatively constant well water
      turbidities and lack of a significant number of detections of microorganisms in
      the well waters. Further research is needed to better understand the
      relationships among transport of pathogens (e.g., Cryptosporidium, Giardia,
      viruses) and potential surrogate parameters (including bacterial spores and
      bacteriophage) during RBF and the effects of water and sediment characteristics
      on removal efficiency.

PMID- 15869780
TI  - Impact of meteorology and energy structure on solvent extractable organic
      compounds of PM2.5 in Beijing, China.
AB  - Twenty-eight PM2.5 samples collected in Summer (July 2002) and Winter (November
      2002) at two sites in Beijing, China were analyzed using GC/MS to investigate the
      impact of meteorology and coal burning on the solvent extractable organic
      compounds (SEOC). The characteristics and abundance of the n-alkanes, polycyclic
      aromatic hydrocarbons (PAHs), n-fatty acids and n-alkanols were determined.
      Source identification was made using organic species as molecular markers. Semi
      volatile compounds of alkanes and PAHs had much higher concentrations in winter
      than summer because of the large difference in the temperature between the
      seasons. Plant wax emission was a major contributor to n-alkanes in summer, but
      fossil fuel residue was a major source (>80%) in winter. The seasonal differences
      in the distribution of pentacyclic triterpanes clearly shows the impact of coal
      burning for space heating in winter. The yield of PAHs in winter (148 ng m(-3) at
      the urban site and 277 ng m(-3) at the suburban site) was six to eight times
      higher than that in summer and was found to be mainly from coal burning. Higher
      pollutant concentrations were measured at the suburban site than the urban site
      in winter due to the rapid expansion of the city limit and the relocation of
      factories from urban to suburban areas over the last two decades.

PMID- 15869781
TI  - Removal of congo red from aqueous solution by bagasse fly ash and activated
      carbon: kinetic study and equilibrium isotherm analyses.
AB  - Present investigation deals with the utilisation of bagasse fly ash (BFA)
      (generated as a waste material from bagasse fired boilers) and the use of
      activated carbons-commercial grade (ACC) and laboratory grade (ACL), as
      adsorbents for the removal of congo red (CR) from aqueous solutions. Batch
      studies were conducted to evaluate the adsorption capacity of BFA, ACC and ACL
      and the effects of initial pH (pH(0)), contact time and initial dye concentration
      on adsorption. The pH(0) of the dye solution strongly affected the chemistry of
      both the dye molecules and BFA in an aqueous solution. The effective pH(0) was
      7.0 for adsorption on BFA. Kinetic studies showed that the adsorption of CR on
      all the adsorbents was a gradual process. Equilibrium reached in about 4h contact
      time. Optimum BFA, ACC and ACL dosages were found to be 1, 20 and 2 g l(-1),
      respectively. CR uptake by the adsorbents followed pseudo-second-order kinetics.
      Equilibrium isotherms for the adsorption of CR on BFA, ACC and ACL were analysed
      by the Freundlich, Langmuir, Redlich-Peterson, and Temkin isotherm equations.
      Error analysis showed that the R-P isotherm best-fits the CR adsorption isotherm
      data on all adsorbents. The Freundlich isotherm also shows comparable fit.
      Thermodynamics showed that the adsorption of CR on BFA was most favourable in
      comparison to activated carbons.

PMID- 15869782
TI  - Isolation and characterization of a diverse group of phenylacetic acid degrading
      microorganisms from pristine soil.
AB  - A diverse range of microorganisms capable of growth on phenylacetic acid as the
      sole source of carbon and energy were isolated from soil. Sixty six different
      isolates were identified and grouped according to 16S rRNA gene RFLP analysis.
      Subsequent sequencing of 16S rDNA from selected strains allowed further
      characterization of the phenylacetic acid degrading population isolated from
      soil. Nearly half (30) of the isolates are Bacillus species while the rest of the
      isolates are strains from a variety of genera namely, Arthrobacter, Pseudomonas,
      Rhodococcus, Acinetobacter, Enterobacter, Flavobacterium, and Paenibacillus.
      Sixty-one of the sixty-six strains reproducibly grew in defined minimal liquid
      culture medium (E2). All strains isolated grew when at least one hydroxylated
      derivative of phenylacetic acid was supplied as the carbon source, while 59 out
      of the 61 strains tested, accumulated ortho-hydroxyphenylacetic acid in the assay
      buffer; when pulsed with phenylacetic acid. Oxygen consumption experiments failed
      to indicate a clear link between phenylacetic acid and hydroxy-substituted
      phenylacetic acid in isolates from a broad range of genera.

PMID- 15869783
TI  - Isotopic evidence for diet and subsistence pattern of the Saint-Cesaire I
      Neanderthal: review and use of a multi-source mixing model.
AB  - The carbon and nitrogen isotopic abundances of the collagen extracted from the
      Saint-Cesaire I Neanderthal have been used to infer the dietary behaviour of this
      specimen. A review of previously published Neanderthal collagen isotopic
      signatures with the addition of 3 new collagen isotopic signatures from specimens
      from Les Pradelles allows us to compare the dietary habits of 5 Neanderthal
      specimens from OIS 3 and one specimen from OIS 5c. This comparison points to a
      trophic position as top predator in an open environment, with little variation
      through time and space. In addition, a comparison of the Saint-Cesaire I
      Neanderthal with contemporaneous hyaenas has been performed using a multi-source
      mixing model, modified from Phillips and Gregg (2003, Oecologia 127, 171). It
      appears that the isotopic differences between the Neanderthal specimen and
      hyaenas can be accounted for by much lower amounts of reindeer and much higher
      amounts of woolly rhinoceros and woolly mammoth in the dietary input of the
      Neanderthal specimen than in that of hyaenas, with relatively similar
      contributions of bovinae, large deer and horse for both predators, a conclusion
      consistent with the zooarchaeological data. The high proportion of very large
      herbivores, such as woolly rhinoceros and woolly mammoth, in Neanderthal's diet
      compare to that of the scavenging hyaenas suggests that Neanderthals could not
      acquire these prey through scavenging. They probably had to hunt for
      proboscideans and rhinoceros. Such a prey selection could result from a long
      lasting dietary tradition in Europe.

PMID- 15869784
TI  - Deletion polymorphism in the gene for angiotensin-converting enzyme is associated
      with essential hypertension in men born during the Pacific War.
AB  - Age is a strong risk factor for hypertension in relation to vascular aging.
      Additional etiological factors include: lifestyle, genetic factors, and their
      interactions. The aim of this study is to examine whether an insertion/deletion
      (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene is associated
      with essential hypertension in Korean born during the Pacific War. A total of
      13,914 healthy subjects (8261 men, 5653 women) aged 20-79 years were examined.
      Subjects with abnormal renal, thyroid dysfunction, or electrolyte levels were
      excluded. Logistic regression analysis showed increased risk (OR=1.15; 95% CI,
      1.01-1.31) in men, but not in women (OR, 1.06; 95% CI, 0.89-1.26). However, after
      adjustment for age, obesity, cholesterol, alcohol consumption, and diabetes
      mellitus, increased risk in men was not significant (OR, 1.13; 95% CI, 0.98
      1.42). Analyzed according to birth-year, DD genotype showed increased risk for
      hypertension in only a subgroup of men (adjusted OR, 1.56; 95% CI, 1.16-2.09; p =
      0.001), born during the Pacific War (1941-1945 year). Findings suggest that the
      ACE DD genotype plays a role in the pathogenesis of essential hypertension, in
      conjunction with adverse environmental conditions in early life, with sex-related
      difference.

PMID- 15869785
TI  - The effect of LMWH (tinzaparin) on coagulation and fibrinolytic activation in
      pregnant women at risk of thrombosis.

PMID- 15869786
TI  - Investigating serpin-enzyme complex formation and stability via single and
      multiple residue reactive centre loop substitutions in heparin cofactor II.
AB  - INTRODUCTION: Following thrombin cleavage of the reactive centre (P1-P1'; L444
      S445) of the serpin heparin cofactor II (HCII), HCII traps thrombin (IIa) in a
      stable inhibitory complex. To compare HCII to other serpins we substituted: the
      P13-P5' residues of HCII with those of alpha(1)-proteinase inhibitor (alpha(1)
      PI), alpha(1)-PI (M358R), or antithrombin (AT); the P4-P1, P3-P1, and P2-P1
      residues of HCII with those of AT; and made L444A/H/K/M or R point mutations. We
      also combined L444R with changes in the glycosaminoglycan binding domain
      collectively termed MutD. MATERIALS AND METHODS: Variants were made by site
      directed mutagenesis, expressed in bacteria, purified and characterized
      electrophoretically and kinetically. RESULTS AND CONCLUSIONS: Of the P13-P5'
      mutants, only the alpha(1)-PI-loop variant retained anti-IIa activity, but less
      than the corresponding L444M. Heparin-catalyzed rate constants for IIa inhibition
      were reduced vs. wild-type (WT) by at most three-fold for all P1 mutants save
      L444A (reduced 20-fold). L444R and L444K inhibited IIa>50- and >6-fold more
      rapidly than WT in heparin-free reactions, but stoichiometries of inhibition were
      increased for all variants. HCII-IIa complexes of all P1 variants were stable in
      the absence of heparin, but those of the L444K and L444R variants released active
      IIa over time with heparin. Limited proteolysis of these two groups of HCII-IIa
      complexes produced different fragmentation patterns consistent with
      conformational differences. The combination of either substituted AT residues at
      P2, P3, and P4, or the MutD mutations with L444R resulted in complex instability
      with or without heparin. This is the first description of HCII-IIa complexes of
      transient stability forming in the absence of heparin, and may explain the extent
      to which the reactive centre loop of HCII differs from that of AT.

PMID- 15869787
TI  - A combination of a thrombin inhibitor and dexamethasone prevents the development
      of experimental disseminated intravascular coagulation in rats.
AB  - INTRODUCTION: Disseminated intravascular coagulation (DIC) is a serious and
      potentially lethal complication of severe sepsis. DIC is characterised primarily
      by widespread platelet aggregation and fibrin deposition, followed by consumption
      of platelets, coagulation factors, and inhibitors. The aim of the study was to
      evaluate the efficacy of the active-site thrombin inhibitor melagatran, the
      active form of the oral direct thrombin inhibitor ximelagatran, in reducing
      fibrinogen and platelet consumption in blood and fibrin deposition in organs, in
      an experimental endotoxinaemia rat model. MATERIALS AND METHODS: In this model,
      DIC was induced by an intravenous injection of endotoxin (1 mg/kg). Melagatran
      was compared with unfractionated heparin and the synthetic glucocorticoid
      analogue dexamethasone. Animals were divided into 16 treatment groups in which
      high and low doses of each agent were tested alone and in combination with
      melagatran. RESULTS: Fibrinogen consumption was reduced by melagatran,
      dexamethasone, and heparin, and was completely prevented by melagatran in
      combination with dexamethasone. Platelet consumption was partially reduced by
      melagatran, unfractionated heparin, and dexamethasone, but complete protection
      was observed only with melagatran in combination with dexamethasone. Melagatran
      in combination with dexamethasone or heparin protected the liver and spleen from
      fibrin deposition. CONCLUSION: In this experimental DIC rat model, the direct
      thrombin inhibitor melagatran given together with dexamethasone protected against
      the consequences of activated haemostasis.

PMID- 15869788
TI  - LPS induced tissue factor expression in the THP-1 monocyte cell line is
      attenuated by conjugated linoleic acid.

PMID- 15869789
TI  - Cholinergic modulation of the urethro genital reflex in spinal cord-transected
      rats.
AB  - The aim of this study was to determine which of the muscarinic receptor subtypes
      are involved in the modulation of the urethrogenital reflex (UGR) in male, spinal
      cord-transected rats. The electromyographic (EMG) responses of the
      bulbospongiosus muscle (BS) to the topical spinal application of muscarine and
      the combination of muscarine and the selective muscarine receptor antagonists
      methoctramine (M2), AFDX (M2), 4DAMP (M3) and tropicamide (M4) were determined
      before and after the elicitation of UGR by way of the mechanical stimulation of
      the urethra. When 50- and 100-mug doses of muscarine were applied without
      urethral stimulation, a rhythmic activity of the BS was observed, similar to the
      one found when UGR was evoked. The M3 and M4 - but not the M2 - antagonists
      prevented BS response to muscarine when urethral stimulation was not performed.
      When UGR was elicited following urethral stimulation muscarine produced an
      increase in burst duration and a decrease in burst frequency. The M2 antagonist
      reverted the effects of muscarine on the UGR, while the M3 and M4 antagonists
      produced a significant increase in the frequency and in the bursts number, when
      compared to the control muscarine response. The differences observed in BS
      responses to muscarine and muscarine antagonists before and after UGR elicitation
      were probably linked to the intrinsic effects of the endogenous acethylcholine
      (Ach) released after urethral stimulation. The present results suggest a
      cholinergic modulation of UGR in spinal cord-transected rats mediated by the M2,
      M3 and M4 muscarinic receptor subtypes.

PMID- 15869790
TI  - Masked priming is abstract in the left and right visual fields.
AB  - Two experiments assessed masked priming for words presented to the left and right
      visual fields in a lexical decision task. In both Experiments, the same magnitude
      and pattern of priming was obtained for visually similar (kiss-KISS) and
      dissimilar (read-READ) prime-target pairs. These findings provide no support for
      the hypothesis that word identification is mediated by separate and lateralized
      abstract and specific visual form systems. Strikingly, equivalent priming was
      observed when primes and targets were presented to the same or opposite visual
      fields, suggesting that priming occurs after visual information from the two
      hemispheres is integrated.

PMID- 15869791
TI  - Promotion of bone formation by simvastatin in polyethylene particle-induced
      osteolysis.
AB  - The effects of statins on bone formation in periprosthetic osteolysis have not
      been determined to date. We investigated the effect of the HMG-CoA reductase
      inhibitor simvastatin on osteoblastic bone formation under conditions of ultra
      high molecular weight polyethylene (UHMWPE) particle-induced osteolysis. The
      murine calvarial osteolysis model was utilized in 21 C57BL/J6 mice randomized to
      three groups. Group I underwent sham surgery only, group II received UHMWPE
      particles, and group III, particles and simvastatin treatment. After 2 weeks,
      calvaria were processed for histomorphometry and stained with Giemsa dye. New
      bone formation was measured as osteoid tissue area within the midline suture.
      Bone thickness was quantified as indicator of net bone growth. Statistical
      analysis was performed using one-way ANOVA and a Student's t-test. New bone
      formation and bone thickness were significantly enhanced following simvastatin
      treatment. New bone formation was 0.008+/-0.008 mm2 in sham controls (group I),
      0.015+/-0.012 mm2 after particle implantation without further intervention (group
      II), compared to 0.083+/-0.021 mm2 with particle implantation and simvastatin
      treatment (group III) (p=0.003). The bone thickness was 0.213+/-0.007 mm in group
      I, 0.183+/-0.005 mm in group II, and 0.238+/-0.009 mm in group III (p=0.00008).
      In conclusion, simvastatin treatment markedly promoted bone formation and net
      bone growth in UHMWPE particle-induced osteolysis in a murine calvarial model.
      These new findings indicate that simvastatin may have favorable osteoanabolic
      effects on wear debris-mediated osteolysis after total joint arthroplasty,
      involving local stimulation of osteoblastic bone formation.

PMID- 15869792
TI  - A virus-neutralising antibody is not cytotoxic in vitro.
AB  - Hybridoma cell lines are characterized by a preferential loss of the heavy chain
      gene. This observation has led to the theory that the immunoglobulin heavy chain
      possesses an intrinsic cytotoxic activity in some cell types. We have generated
      transgenic mice expressing the heavy and light chain genes of the virus
      neutralising antibody A1 carrying constant domains of the human gamma1 and kappa
      isotype. Heavy chain and light chain transgenes were under trancriptional control
      of identical promoter regions derived from the mammary gland specific ovine beta
      lactoglobulin gene. The copy number of the heavy chain transgene was consistently
      lower than the copy number of the light chain gene in all lines of transgenic
      mice. Moreover, the light chain gene was expressed in significant excess of the
      heavy chain gene in the lactating mammary gland in all transgenic lines. In
      several transgenic lines, the differences in antibody expression were greater
      than could be explained by the differences in transgene copy number. One
      potential cause of this phenotype could be a cytotoxic effect of free heavy chain
      protein in embryonic cells (resulting in differences in copy number) or mammary
      epithelial cells (resulting in differences in transgene expression). We therefore
      directly assessed the effect of the expression of free A1 heavy chain protein in
      epithelial cell lines and in murine embryonic stem cells. However, full-length A1
      heavy chain mRNA and protein could be expressed transiently and stably in both
      epithelial and embryonic stem cells and had no detectable effect on cell
      viability. Taken together, these findings argue against an inherent cytotoxicity
      of the free A1 heavy chain protein in epithelial or embryonic cells.

PMID- 15869793
TI  - Genomic structure, promoter analysis and expression of the porcine (Sus scrofa)
      TLR4 gene.
AB  - Toll-like receptor 4 (TLR4) is essential for initiating the innate response to
      lipopolysaccharide (LPS) from Gram-negative bacteria by acting as a signal
      transducing receptor. As the pig industry faces a unique array of related
      pathogens, it is anticipated that the genotype of swine TLR4 could be of crucial
      importance in future strategies aimed at improving genetic resistance to
      infectious diseases. In order to help in investigating TLR4 as a candidate
      disease-resistance gene in pigs, we established its genomic structure and
      produced sufficient flanking intronic sequences to enable simple PCR
      amplification of the coding portions of the gene. Expression in different porcine
      tissues was studied and showed splicing variations in mRNA sequences. The cDNA
      sequence for poTLR4 contains an open reading frame of 2526bp that codes for 841
      aa, 98 and 568bp in the 5'- and 3'-UTRs, respectively. Overall, the general
      organization of porcine, human, murine, and avian TLR4 genes is quite similar:
      three exons with the third one very long. A high level of conservation of the
      size and the sequence, especially for the two last exons and particularly in the
      sequence corresponding to the LRRs and TIR domain, is observed between species.
      The important antimicrobial properties of these proteins may account for a
      conservative selection pressure on these TLR4 coding sequences. Several putative
      binding sites described in the human and murine promoter of TLR4 genes have been
      identified in the 5'-flanking region of poTLR4. Conversely, this region lacks a
      TATA box, consensus initiator sequences, or GC-rich regions. The basic sequence
      data gathered will allow the establishment of an inventory of naturally occurring
      variation in porcine TLR4, so that alleles can be tested for disease association
      studies.

PMID- 15869794
TI  - Lipopolysaccharide-induced c-Src expression plays a role in nitric oxide and
      TNFalpha secretion in macrophages.
AB  - As tyrosine kinases are indispensable in lipopolysaccharide (LPS)-induced
      macrophage activation, the myeloid-specific Src members (i.e. Lyn, Fgr and Hck)
      are speculated to play important roles in this process. However, the normal LPS
      responsiveness in lyn(-/-)fgr(-/-)hck(-/-) macrophages implicates the presence of
      an elusive, compensating tyrosine kinase(s). In this study, we demonstrate the
      upregulation of c-Src in Raw264.7 and peritoneal macrophages (PEMs) by LPS, which
      is inhibited by PP2 (an inhibitor for Src family kinases),
      pyrrolidinedithiocarbamate (PDTC; NF-kappaB inhibitor) and LY294002 (PI3K
      inhibitor). And this LPS-mediated c-Src induction is also observed in macrophages
      recovered from LPS-challenged rats. Intriguingly, PP2 attenuates the ability of
      PEMs to elicit COX-2 expression and nitric oxide production in response to LPS.
      Similar results are also observed when macrophages recovered from rats receiving
      either LPS alone or LPS and PP2 both are compared. Furthermore, administration of
      PP2 in Raw264.7 and animal models of sepsis greatly suppresses TNFalpha secretion
      and serum TNFalpha level, respectively. Therefore, we conclude that c-Src, with
      its LPS induction, has an unperceived role in transmitting LPS signaling in
      macrophages.

PMID- 15869795
TI  - Mitochondrial mediated thimerosal-induced apoptosis in a human neuroblastoma cell
      line (SK-N-SH).
AB  - Environmental exposure to mercurials continues to be a public health issue due to
      their deleterious effects on immune, renal and neurological function. Recently
      the safety of thimerosal, an ethyl mercury-containing preservative used in
      vaccines, has been questioned due to exposure of infants during immunization.
      Mercurials have been reported to cause apoptosis in cultured neurons; however,
      the signaling pathways resulting in cell death have not been well characterized.
      Therefore, the objective of this study was to identify the mode of cell death in
      an in vitro model of thimerosal-induced neurotoxicity, and more specifically, to
      elucidate signaling pathways which might serve as pharmacological targets. Within
      2 h of thimerosal exposure (5 microM) to the human neuroblastoma cell line, SK-N
      SH, morphological changes, including membrane alterations and cell shrinkage,
      were observed. Cell viability, assessed by measurement of lactate dehydrogenase
      (LDH) activity in the medium, as well as the 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) assay, showed a time- and concentration
      dependent decrease in cell survival upon thimerosal exposure. In cells treated
      for 24 h with thimerosal, fluorescence microscopy indicated cells undergoing both
      apoptosis and oncosis/necrosis. To identify the apoptotic pathway associated with
      thimerosal-mediated cell death, we first evaluated the mitochondrial cascade, as
      both inorganic and organic mercurials have been reported to accumulate in the
      organelle. Cytochrome c was shown to leak from the mitochondria, followed by
      caspase 9 cleavage within 8 h of treatment. In addition, poly(ADP-ribose)
      polymerase (PARP) was cleaved to form a 85 kDa fragment following maximal caspase
      3 activation at 24 h. Taken together these findings suggest deleterious effects
      on the cytoarchitecture by thimerosal and initiation of mitochondrial-mediated
      apoptosis.

PMID- 15869796
TI  - Effects of Tris and Hepes buffers on the interaction of palladium-diaminopropane
      complexes with DNA.
AB  - The Pd(II) complexes, [PdCl(2)(1,2-pn)] and [PdCl(2)(1,3-pn)] (pn is
      diaminopropane), were synthesized and characterized by analytical and
      spectroscopic (FT-IR, (1)H NMR and (13)C NMR) techniques. UV difference spectral
      study performed on Pd-pn/DNA systems, indicate a pronounced interaction of
      palladium complexes with DNA in cell-free media; comparison of lambda(max),
      Abs(max) and %H values observed for the two compounds might be attributed to
      structural differences of the chelated ligand rings. Results obtained from
      electrophoretic analysis of Pd complexes in presence of pBR322 plasmid DNA show a
      clear decreasing of the supercoiled (SC) DNA form mobility, that could be
      attributed to unwinding of the double helix; a parallel increasing of the open
      circular (OC) DNA form mobility is also noted, this fact implying that the
      binding of complexes either shortens or condenses the DNA helix. Interaction
      studies of Pd complexes with plasmid DNA in different buffer systems indicate
      that DNA binding efficiency capable of modifying the tertiary structure of pBR322
      decreased from NaClO(4) to Hepes 2, Hepes 1 [Hepes=4-(2-hydroxyethyl)-1
      piperazineethanesulfonic acid], and Tris [(hydroxymethyl)aminomethane] buffers,
      in this order. Moreover, the level of DNA modifications produced by palladium
      complexes in 10 mM NaClO(4) remains unchanged after transferring the samples into
      the medium required for subsequent biophysical or biochemical analyses.

PMID- 15869797
TI  - Probing the potential of platinum(II) complexes for the inhibition of thiol
      dependent enzymatic activity.
AB  - The synthesis and biological evaluation of platinum(II) amine complexes designed
      to act as inhibitors of the human cysteine protease cathepsin B, a thiol
      dependent enzyme, is described. The complexes, composed of a cathepsin targeting
      ligand and a platinum(II) moiety with varying degrees of reactivity towards
      nucleophiles were characterized by physical-analytical methods and a proof of
      principle was illustrated in a model reaction. In biological tests for inhibitory
      activity against cathepsin B the presented compounds did not show significant
      inhibitory activity.

PMID- 15869798
TI  - Examination of the molecular nature of low-molecular-mass chromium(III) ions in
      isolated osteoarthritic knee-joint synovial fluid.
AB  - High field (1)H NMR spectroscopy demonstrated that equilibration of added Cr(III)
      ions in osteoarthritic knee-joint synovial fluid (SF) resulted in its
      complexation by a range of biomolecules, the relative efficacies of these
      complexants/chelators being threonine approximately
      alanine>glycine>glutamine>citrate>histidine approximately phenylalanine
      approximately tyrosine>valine approximately isoleucine approximately
      leucine>glutamate>lactate approximately acetate approximately formate
      approximately pyruvate, this order reflecting the ability of these ligands to
      compete for the available Cr(III) in terms of (1) thermodynamic equilibrium
      constants for the formation of their complexes and (2) their SF concentrations.
      The significance of these observations with regard to the in vivo corrosion of
      chromium-containing metal alloy joint prostheses (e.g., CoCr alloys) is
      discussed.

PMID- 15869799
TI  - Structural study of ribonucleotide reductase inhibitor hydrazones. Synthesis and
      X-ray diffraction analysis of a copper(II)-benzoylpyridine-2-quinolinyl hydrazone
      complex.
AB  - Single crystals as yellow needles of N-(4,8-dimethyl-quinolin-2-yl)-N'-(1-pyridin
      2-yl-ethylidene)-hydrazine, HL(1), 1, and N-(4-methyl-quinolin-2-yl)-N'-(phenyl
      pyridin-2-yl-methylene)-hydrazine, HL(2), 2, were obtained from methanol (MeOH)
      and analyzed via X-ray diffraction (XRD). HL(2) reacted with copper(II) acetate
      to produce a dark red powder that gave single crystals of
      [Cu(L(2))(OOCCH(3))].0.9C(6)H(5)CH(3), 3.0.9C(6)H(5)CH(3) when recrystallized
      from toluene. The conformation of the N(quinolinyl,q)-C(q)-N(H)-N(imine,i)-C
      C(pyridine,p)-N(p) grouping is trans,trans,trans,trans or tttt, and ttcc for 1
      and 2, respectively, at the solid state, as revealed via single crystal X-ray
      diffraction. Thus, the structure of 1 has the methyl (hydrazone) group syn to the
      N-H bond and syn to the N(q) and N(p) atom. On the other side, the structure of 2
      is stabilized by a strong intra-molecular N-H...N hydrogen bond which involves
      the pyridyl nitrogen atom. The molecule 1 is almost planar, the torsion angles do
      not deviate more than 4 degrees from the idealized values of 0 degrees and 180
      degrees . In the structure of 2 the pyridyl ring is almost coplanar with the N(q)
      C(q)-NH-N(i)-C system, whereas the phenyl (Ph) ring is twisted by ca. 55 degrees
      . The structure of 3 has the L(2) ligand as deprotonated at the N-N function and
      in a cttc conformation as opposite to the ttcc one found for pure 2. The metal
      center is coordinated through N(q), N(i), N(p) and through an oxygen atom from a
      carboxylate anion. The molecular modeling analysis of 1 and 2 (semi-empirical
      molecular orbital at Zerner's intermediate neglect of differential overlap
      (ZINDO/1) level and density functional theory (DFT) methods) gave good agreement
      with the X-ray structures. Semi-empirical quantum mechanics analysis of 3 allowed
      to assign the UV-Vis spectrum that is characterized by strong absorptions in the
      visible, UVA and UVB regions. Owing to the ribonucleotide reductase inhibitory
      activity of the ligand, to the ascertained anticancer activity shown previously
      by related copper(II)-hydrazone complexes, and to the oxygen radical scavenger
      activity of several copper(II)-complexes, 3 is potentially anticancer and anti
      inflammatory.

PMID- 15869800
TI  - Synthesis, characterization and DNA-binding properties of a new cobalt(II)
      complex: Co(bbt)2Cl2.
AB  - A new bis(N-benzyl-benzotriazole)dichloro Co(II) complex (Co(bbt)(2)Cl(2)) was
      synthesized and the structure was characterized by X-ray crystallography, IR
      spectrum and elemental analysis. The electrochemical characterization of
      Co(bbt)(2)Cl(2) was measured in detail, and the interaction of this Co(II)
      complex with fish sperm DNA was studied by electrochemical techniques and
      ultraviolet-visible (UV-Vis) spectrophotometry. The cyclic voltammetry (CV)
      showed that Co(bbt)(2)Cl(2) had two reduction peaks and one oxidation peak on
      gold electrode. It was found that the currents of both the reduction peaks and
      the oxidation peak decreased significantly in the presence of DNA compared with
      those in the absence of DNA, which indicated that Co(bbt)(2)Cl(2) could interact
      with DNA. The binding of DNA with the complex was not only electrostatic binding
      but also intercalation.

PMID- 15869801
TI  - Functional analysis of a single nucleotide polymorphism in a potential binding
      site for GATA transcription factors in the ovine interleukin 2 gene.
AB  - The transcription factor GATA-3 is one regulator of Th1/Th2 differentiation. In
      sheep, we recently discovered a putative GATA-binding site (WGATAR) in the second
      intron of the Th1-cytokine gene interleukin 2 (IL2), showing a single nucleotide
      polymorphism (G/C). As genetic variations in cytokine genes are thought to
      regulate cytokine production, we studied the significance of this polymorphism
      for IL2 transcription. Sheep with different IL2 genotypes were identified by
      single-strand conformation polymorphism (SSCP)-analysis and IL2 transcription
      levels in peripheral blood mononuclear cells (PBMC) isolated from these animals
      were compared. For this purpose, transcription of IL2 mRNA was quantified by real
      time polymerase chain reaction in unstimulated PBMC and in PBMC incubated for 4h
      in the presence of concanavalin A (ConA) or phorbol 12-myristate 13-acetate plus
      ionomycin (PMA/I). Compared to unstimulated cells, stimulation with ConA and
      PMA/I increased the IL2 mRNA transcription in average by 300- and 20-fold,
      respectively. Nevertheless, no significant differences in IL2 transcription
      between the genotypes could be detected. These findings were confirmed by band
      shift studies using different oligonucleotides containing variations of the
      potential binding motif, which showed no differences in the gel mobility after
      incubation with nuclear extract containing GATA-3. The obtained results argue
      against an impact of this polymorphism on the IL2 transcription and the genetic
      disease resistance in sheep.

PMID- 15869802
TI  - Mannosylated niosomes as adjuvant-carrier system for oral genetic immunization
      against hepatitis B.
AB  - Aim of the present study was to develop mannosylated niosomes as oral DNA vaccine
      carriers for the induction of humoral, cellular and mucosal immunity. Niosomes
      composed of span 60, cholesterol and stearylamine as constitutive lipids were
      prepared by reverse phase evaporation method and were coated with a modified
      polysaccharide o-palmitoyl mannan (OPM) in order to protect them from bile salt
      caused dissolution and enzymatic degradation in the gastrointestinal tract and to
      enhance their affinity towards the antigen presenting cells of Peyer's patches.
      Prepared niosomes were characterized in vitro for their size, shape, entrapment
      efficiency, ligand binding specificity and stability in simulated gastric fluid
      and simulated intestinal fluid. OPM coated niosomes were found to better stable
      in simulated GIT conditions. The immune stimulating activity was studied by
      measuring serum anti-HBsAg titer, secretory IgA level in intestinal and salivary
      secretions and cyokines level (IL-2 and IFN-gamma) in spleen homogenates
      following oral administration of niosomal formulations in Balb/c mice and
      compared with naked DNA as well as pure recombinant HBsAg injected
      intramuscularly. The serum anti-HBsAg titer obtained after oral administration of
      OPM coated niosomal formulations was although less as compared to that elicited
      by naked DNA and pure HBsAg administered intramuscularly, but the mice were
      seroprotective within 2 weeks and antibody level far above the clinically
      protective limit for humans was achieved. Intramuscular naked DNA and recombinant
      HBsAg did not elicited sIgA titer in mucosal secretions that was induced by oral
      administration of OPM coated niosomes. Similarly, cellular response (cytokines
      level) was absent in pure HBsAg treated animals. OPM coated niosomes produced
      humoral (both systemic and mucosal) and cellular immune response upon oral
      administration. The study signifies the potential of OPM coated niosomes as DNA
      vaccine carrier and adjuvant for effective oral immunization.

PMID- 15869803
TI  - Susceptibility of corneal allografts and xenografts to antibody-mediated
      rejection.
AB  - The effects of passive transfer of antisera containing cytotoxic antibodies to
      allo- and xenoantigens on survival of corneal allografts and xenografts were
      evaluated in experimental models. Corneas from allogeneic B10 or xenogeneic rat
      Lewis donors were grafted orthotopically into BALB/c mice. Recipient mice were
      treated with donor-specific antisera administered at the period of grafting or at
      2 weeks after transplantation. Rejection was determined by the severity of
      corneal opacity using a standard scoring system. Treatment of graft recipients
      with donor-specific antisera accelerated the onset of graft rejection and
      significantly shortened survival times of both corneal allografts and xenografts.
      Corneal xenografts, which had been accepted after treatment with anti-CD4
      monoclonal antibody, were acutely rejected by the passive transfer of antiserum
      against xenoantigens. The results suggest that corneal grafts are vulnerable to
      antibody-dependent immunity and that cytotoxic antibodies against graft donor
      antigens can mediate rejection of both corneal allografts and xenografts.

PMID- 15869804
TI  - Origin and anti-tumor effects of anti-dsDNA autoantibodies in cancer patients and
      tumor-bearing mice.
AB  - In the present investigation, we detected anti-dsDNA autoantibodies in cancer
      patients and modeled the production of anti-dsDNA autoantibodies by inoculating
      tumors in BALB/c mice. Moreover, induction of anti-dsDNA autoantibodies by
      immunization with inactivated tumor cells and their DNA indicated that DNA of
      tumor cells was probably the primary antigen, which was supported by the
      significantly increasing levels of sera free DNA in cancer patients and tumor
      bearing mice. cELISA and indirect immunofluorescence assay showed that the anti
      dsDNA autoantibodies could bind to the surface components of tumor cells. In
      vitro assay showed that immunosera at week 6 from immunized mice displayed
      significant cytotoxicity to tumor cells compared to that of negative control, but
      no cytotoxicity mediated by immunosera at week 22 was observed. In addition, by
      flow cytometry and electrophoresis of fragmented DNA, the cytotoxicity might
      probably be mediated by apoptosis. Our data also showed that the ability of the
      anti-dsDNA autoantibodies to induce apoptosis of SP2/0 and Wehi 164 cells was
      significantly correlated (r = 0.990, p < 0.01 and r = 0.901, p < 0.05) with their
      functional affinity. In vivo, the growth of solid tumors was significantly
      inhibited in the immunized mice inoculated directly with SP2/0 and Wehi 164
      cells, or in the naive mice which were inoculated with SP2/0 cells preincubated
      with immunosera containing anti-dsDNA autoantibodies. In conclusion, we
      demonstrated the origin of anti-dsDNA autoantibodies in cancer patients and tumor
      bearing mice. And our data also showed that these autoantibodies revealed anti
      tumor effect by inducing apoptosis.

PMID- 15869805
TI  - Neuroinflammatory responses from microglia recovered from HIV-1-infected and
      seronegative subjects.
AB  - Microglial and macrophage infection and immune activation underlie the
      pathogenesis of HIV-1-associated dementia (HAD). To assess microglial function in
      HAD, we isolated cells from brain tissues recovered from an HIV-1-infected
      patient within 4 h of death. Brain tissue from seronegative patients served as
      controls. Regional neuropathology was correlated to microglial function. HIV-1
      patient microglia formed multinucleated giant cells and produced progeny virions.
      These microglia secreted reduced basal and LPS-stimulated TNF-alpha levels
      compared to controls. Monocytes from seronegative donors paralleled these
      diminished immune responses following repeated LPS-activation. These results
      demonstrate changes in innate microglial function following viral infection or
      chronic immune activation.

PMID- 15869806
TI  - The effects of estradiol and progesterone on the synthesis of collagen in
      tracheal surgery.
AB  - OBJECTIVE: Estrogen and progesterone have the decreasing effect on massive
      collagen synthesis in wound healing. Here, it is aimed to determine their
      decreasing effect on collagen accumulation and fibroblast proliferation in
      trachea histologically and to understand if they would be protective for tracheal
      stenosis. METHODS: Thirteen male Winstar rats were divided randomly into two
      groups: estrogen-progesterone group (group 1, eight rats) and control group
      (group 2, five rats). Under general anesthesia, tracheas were incised vertically
      extending from second to fifth tracheal ring. Incision was closed with absorbable
      sutures. Estrodiol benzoat and progesterone was given intramuscularly to estrogen
      progesterone group, saline solution to control group. After 4 weeks they were
      sacrificed and tracheas were excised. Horizontal cross section of the narrowest
      part of the incised trachea was examined histologically. Epithelial regeneration,
      inflammatory cell infiltration, angiogenesis, fibroblast proliferation and
      collagen deposition were evaluated by histological grading. RESULTS:
      Statistically significant difference was found between the groups in collagen
      deposition and fibroblast proliferation (p=0.011, <0.05). For epithelial
      regeneration, inflammatory cell infiltration, and angiogenesis there was no
      difference. CONCLUSION: As a result, it was proved that sex hormones inhibit
      massive collagen deposition and fibroblast proliferation in wound healing of
      tracheal surgery. Hence, they may prevent tracheal stenosis.

PMID- 15869807
TI  - Congenital stridor secondary to an upper airway cyst in a patient with Ellis-van
      Creveld syndrome.
AB  - We report the occurrence of a pyriform sinus cyst in a patient with Ellis-van
      Crevald syndrome. The patient presented with congenital stridor. The cyst was
      drained but recurred. MRI scanning revealed extensive involvement in the neck.
      Marsupialization and CO2 laser ablation of the lesion was successful, and the
      patient remained free of symptoms. Although oral lesions have been described in
      association with this syndrome, to our knowledge this is the first case report of
      an upper airway cyst in a patient with the Ellis-van Crevald syndrome.

PMID- 15869808
TI  - Methicillin-resistant Staphylococcus aureus as a pathogen in deep neck abscesses:
      a pediatric case series.
AB  - OBJECTIVES: Pediatric deep neck space abscesses are frequently treated by the
      otolaryngologist. We report four children with deep neck abscesses caused by
      methicillin-resistant Staphylococcus aureus (MRSA), including the first described
      case of descending mediastinitis caused by MRSA in a child. METHODS: Records from
      March 2001 to April 2002 were reviewed. RESULTS: Four patients presented with
      neck swelling, and three of these also had leukocytosis. All abscess cultures
      were positive for MRSA. Abscess drainage with antibiotic therapy successfully
      treated three cases without complication. The fourth case developed descending
      mediastinitis but survived after additional surgical treatment and prolonged
      antibiotic therapy. CONCLUSIONS: MRSA should be considered as a potential
      pathogen in deep neck space abscesses. A high index of suspicion is needed as
      well as aggressive treatment including incision and drainage along with culture
      directed medical therapy. Surgical drainage may be the most important aspect of
      therapy.

PMID- 15869809
TI  - Comparisons of steroid, acyclovir, lipoprostoglandin E1 and steroid + acyclovir
      treatments in facial paralysis: a rat study.
AB  - OBJECTIVE: To induce experimental peripheral facial paralysis by inoculation of
      HSV1 and to compare the effects of steroid, acyclovir, lipoprostoglandin E2 and
      steroid + acyclovir treatments in terms of clinical recovery,
      electrophysiologically and histopathologically. MATERIALS AND METHODS: A total of
      132 adult female rats were used in this study. HSV type 1 strain was inoculated
      at the back of the left ear by using 27 gauge needle. Of all animals, 70 (53%)
      rats which developed facial paralysis were divided into five groups (n = 14 for
      each group) as control, steroid + acyclovir, lipoprostaglandin E1, steroid only
      and acyclovir only. At the end of the 21 days period, the rats were clinically
      examined and electrophysiological tests were performed, then decapitated and the
      nerve specimens were obtained. RESULTS: A modified electroneurography (ENoG) test
      was performed and the latencies and the amplitudes were compared. The findings of
      the intact side were better, but with no significant difference.
      Histopathologicaly edema was significantly smaller in all groups compared to the
      controls (p < 0.05). Similarly, no difference was seen in terms of vacuolar
      degeneration and Schwann cell hyperchromatisation among the groups and no
      significant difference in recovery period and rate of facial paralysis when all
      groups were compared. CONCLUSION: Facial paralysis induced by HSV1 recovered
      spontaneously within a week. In the treatment of facial paralysis, steroid alone,
      acyclovir alone, steroid + acyclovir, or lipoprostaglandin E1 all reduced edema
      in the infected facial nerve but there was no statistical difference in of the
      rate or degree of recovery.

PMID- 15869810
TI  - Susceptibility of bovine mesenchymal stem cells to bovine herpesvirus 4.
AB  - Bovine herpesvirus 4 (BoHV-4) is a gamma herpesvirus with no clear disease
      association. Previous studies have demonstrated that macrophages can harbour
      persistent BoHV-4. Since mesenchymal stem cells in bone marrow regulate the
      differentiation and proliferation of adjacent haematopoietic precursors, such as
      macrophages, the interaction between BoHV-4 and mesenchymal stem cells was
      investigated. Primary bovine mesenchymal stem cells were highly permissive to
      support full replication of BoHV-4. This finding could be considered a new
      important step in studies on the potential pathogenesis related to BoHV-4.

PMID- 15869811
TI  - The olive leaf extract exhibits antiviral activity against viral haemorrhagic
      septicaemia rhabdovirus (VHSV).
AB  - A commercial plant extract derived from olive tree leaf (Olea europaea) (LExt)
      and its major compound, oleuropein (Ole), inhibited the in vitro infectivity of
      the viral haemorrhagic septicaemia virus (VHSV), a salmonid rhabdovirus.
      Incubation of virus with LExt or Ole before infection reduced the viral
      infectivity to 10 and 30%, respectively. Furthermore, LExt drastically decreased
      VHSV titers and viral protein accumulation (virucidal effect) in a dose dependent
      manner when added to cell monolayers 36 h post-infection. On the other hand, both
      the LExt and Ole were able to inhibit cell-to-cell membrane fusion induced by
      VHSV in uninfected cells, suggesting interactions with viral envelope. Therefore,
      we propose that O. europaea could be used as a potential source of promising
      natural antivirals, which have demonstrated to lack impact on health and
      environment. In addition, Ole could be used to design other related antiviral
      agents.

PMID- 15869812
TI  - TBT toxicity on a natural planktonic assemblage exposed to enhanced ultraviolet-B
      radiation.
AB  - A microcosm approach was designed to study the combined effects of tributyltin
      (TBT) from antifouling paints and ultraviolet-B radiation (UVBR: 280-320 nm), on
      a natural planktonic assemblage (<150 microm) isolated from the St. Lawrence
      Estuary at the end of the springtime. Microcosms (9l, cylindrical Teflon bags, 75
      cm heightx25 cm width) were immersed in the water column of mesocosms (1800 l,
      polyethylene bags, 2.3 m depth) and exposed to two different UVBR regimes:
      natural ambient UVBR (NUVBR), and enhanced level of UVBR (HUVBR). During
      consecutive 5 days, effects of TBT (120 ng l -1) and enhanced UVBR (giving a
      biologically weighted UVBR 2.15-fold higher than natural light condition) were
      monitored in the samples coming from following treatments: (i) NUVBR light
      condition without TBT (NUVBR), (ii) NUVBR light condition with TBT-added
      (NUVBR+TBT), (iii) HUVBR light condition without TBT (HUVBR) and (iv) HUVBR light
      condition with TBT-added (HUVBR+TBT). Each treatment was conducted in triplicate
      microcosms. Different parameters were then measured during 5 days, including TBT
      analysis, bacterial abundance and productivity, phytoplankton abundance, cellular
      characteristics and growth rates, as well as in vivo chlorophyll a (Chl a)
      fluorescence. Following TBT addition (NUVBR+TBT treatment), Chl a concentrations
      never exceeded 1 microg l-1 whereas final values as high as 54 microg l-1 were
      observed in TBT-free treatments (NUVBR and HUVBR). TBT addition resulted also in
      the lost of fluorescence signal of the maximum efficiency of the photosystem II
      in phytoplankton assemblage. TBT toxicity caused on phytoplankton <20 microm an
      increase of mean cell size and changes in shape reflected a drastic disturbance
      of the cell cycle leading to an inhibition of the apparent growth rate. These
      negative effects of TBT resulted in a final abundance of phytoplankton <20 microm
      of 591+/-35 cells ml-1 in NUVBR+TBT relative to NUVBR treatment (i.e., 31,846+/
      312 cells ml-1). Moreover, when cells were submitted to TBT under enhanced UVBR
      (HUVBR+TBT treatment), final abundance of phytoplankton <20 microm was only 182+/
      90 cells ml-1, with a significant interaction between TBT and UVBR during the
      last 2 days of the experiment. The same type of interaction was also observed for
      bacterial abundance in NUVBR+TBT and HUVBR+TBT with stimulation of 226 and of
      403%, respectively due to TBT addition relative to NUVBR treatment. When
      considering bacterial productivity, TBT addition resulted in an inhibition of
      32%, and this inhibition was significantly more pronounced under dual stresses
      (i.e., 77% in HUVBR+TBT). These results clearly demonstrate that the combination
      of TBT and UVBR stresses have synergistic effects affecting the first trophic
      levels of the marine food web.

PMID- 15869813
TI  - Carbonylation and glutathionylation of proteins in the blue mussel Mytilus edulis
      detected by proteomic analysis and Western blotting: Actin as a target for
      oxidative stress.
AB  - Protein expression profiles (PEPs) were generated by two-dimensional
      electrophoresis (2-D SDS-PAGE) for gill and digestive glands of Mytilus edulis
      sampled from a polluted and reference site in Cork Harbour, Ireland. Similar
      patterns and expression levels were found for both sites in silver stained gels.
      However, Western blotting for carbonylated proteins demonstrated higher levels of
      specific carbonylation of proteins in tissues from animals in the polluted site.
      Animals from the reference site were acclimated in holding tanks, exposed to 1 mM
      H2O2 for 24 h, dissected and analysed by 2-D SDS-PAGE. Again, generally similar
      PEPs were found in control and exposed animals for gill and digestive gland but
      carbonylation was more pronounced in polluted and exposed animals. Western
      blotting of extracts after one-dimensional electrophoresis with antibodies to
      glutathione and actin revealed that gill proteins are glutathionylated more
      strongly than digestive gland and that this process is more pronounced in
      polluted animals than in controls. We conclude that carbonylation and
      glutathionylation can occur in gill and digestive gland in response to oxidative
      stress in M. edulis. Actin is a major target for both glutathionylation and
      carbonylation under oxidative stress conditions.

PMID- 15869814
TI  - Parasitic nematodes have two distinct chitin synthases.

PMID- 15869815
TI  - Identification, expression, localization and serological characterization of a
      tryptophan-rich antigen from the human malaria parasite Plasmodium vivax.
AB  - Plasmodium vivax is most common but non-cultivable human malaria parasite which
      is poorly characterized at the molecular level. Here, we describe the
      identification and characterization of a P. vivax Tryptophan-Rich Antigen
      (PvTRAg) which contains unusually high (8.28%) tryptophan residues and is
      expressed by all blood stages of the parasite. The pvtrag gene comprises a 978bp
      open reading frame interrupted by two introns. The first intron is located in the
      5'-untranslated region while the second one is positioned 174bp downstream to the
      ATG codon. The encoded approximately 40kDa protein contains a transmembrane
      domain near the N-terminus followed by a tryptophan-rich domain with
      significantly high surface probability and antigenic index. It is localized in
      the parasite cytoplasm as well as in the cytoplasm of the parasitized
      erythrocyte. The purified E. coli expressed recombinant PvTRAg protein showed a
      very high seropositivity rate for the presence of antibodies amongst the P. vivax
      patients, indicating that the antigen generates significant humoral immune
      response during the natural course of P. vivax infection. Analysis of various
      field isolates revealed that the tryptophan-rich domain is highly conserved
      except for three-point mutations. The PvTRAg could be a potential vaccine
      candidate since similar tryptophan-rich antigens of P. yoelii have shown
      protection against malaria in murine model.

PMID- 15869817
TI  - Synthesis and conformational properties of phosphopeptides related to the human
      tau protein.
AB  - In the brains of Alzheimer's disease patients, the tau protein dissociates from
      the axonal microtubule and abnormally aggregates to form a paired helical
      filament (PHF). One of the priorities in Alzheimer research is to determine the
      effects of abnormal phosphorylation on the local structure. A series of peptides
      corresponding to isolated regions of tau protein have been successfully
      synthesized using Fmoc-based chemistry and their conformations were determined by
      1H NMR spectroscopy and circular dichroism (CD) spectroscopy. Immunodominant
      peptides corresponding to tau-(256-273), tau-(350-367) and two phosphorylated
      derivatives in which a single Ser was phosphorylated at positions 262 and 356,
      respectively, were the main focus of the study. A direct alteration of the local
      structure after phosphorylation constitutes a new strategy through which control
      of biological activity can be enforced. In our study on Ser262 in R1 peptide and
      Ser356 in R4 peptide, phosphorylation modifies both the negative charge and the
      local conformation nearby the phosphorylation sites. Together, these structural
      changes indicate that phosphorylation may act as a conformational switch in the
      binding domain of tau protein to alter specificity and affinity of binding to
      microtubule, particularly in response to the abnormal phosphorylation events
      associated with Alzheimer's disease.

PMID- 15869819
TI  - Emergence of Rsv-resistance breaking Soybean mosaic virus isolates from Korean
      soybean cultivars.
AB  - Twelve Rsv resistance-breaking (RB) isolates of Soybean mosaic virus (SMV) were
      obtained from field-grown soybean plants showing mosaic symptoms and subsequently
      examined biologically and molecularly. All of these RB isolates were identified
      as SMV based on serological and infectivity assays, and the amplification of P1
      gene products by reverse transcription-polymerase chain reaction (RT-PCR).
      Differential soybean cultivars, lines or accessions Lee 68 (rsv), PI 96983, York,
      Marshall, Ogden, Kwanggyo, Suweon 97 (Rsv1 alleles), L29 (Rsv3), and V94-5152
      (Rsv4), following inoculation with each RB isolate, showed similar systemic
      symptoms suggesting that these RB isolates can overcome Rsv resistance at three
      loci. To differentiate the 12 RB isolates molecularly, the P1 coding region for
      each isolate was amplified, cloned, sequenced and compared to known SMV strains.
      The P1 region from the RB isolates shared 86-90% and 90-99% similarities in amino
      acid (aa) and nucleotide sequence, respectively, with known SMV strains.
      Comparison of aa sequences indicated that these RB isolates are newly emerging
      isolates capable of breaking Rsv resistance. Phylogenetic analysis further
      suggested that the RB isolates can be classified as three major types. However,
      recombination was not observed within the coding region of P1 protein among the
      types. This is the first report on the emergence of SMV isolates capable of
      overcoming all of the known resistance alleles at the Rsv1 locus, as well as
      distinct resistance genes at Rsv3 and Rsv4.

PMID- 15869818
TI  - Inhibitory influence of chromogranin A N-terminal fragment (vasostatin-1) on the
      spontaneous contractions of rat proximal colon.
AB  - Very little is known about the role played by CGA and its fragments in the
      gastrointestinal physiology. We have studied the role of CGA N-terminal fragments
      in the regulation of intestinal smooth muscle contractility by measuring the
      influence of recombinant CGA 1-78 (VS-1) and synthetic CGA 7-57 peptides on the
      spontaneous mechanical activity of rat proximal colon in vitro. The mechanical
      activity was recorded as changes in the intraluminal pressure. VS-1 (0.1-30 nM)
      and CGA 7-57 (10-300 nM) produced concentration-dependent inhibitory effects,
      characterized by a progressive decrease in the mean amplitude of circular muscle
      spontaneous contractions, without affecting the resting tone. The response to VS
      1 was antagonised by anti-CGA monoclonal antibodies (mAb5A8, B4E11, 7D1 or 4D5)
      but not by an irrelevant antibody, indicating that the effect was specific. The
      inhibitory responses to VS-1 and to CGA 7-57 were significantly reduced by pre
      treatment of the preparations with N(omega)-nitro-l-arginine methyl ester (l
      NAME) (300 microM), 1H-(1,2,4) oxadiazolo-(4,3-a) quinoxalin-1-one (ODQ) (10
      microM), apamin (0.1 microM) or tetrodotoxin (TTX) (1 microM). The results
      suggest that VS-1 plays an inhibitory modulatory role on spontaneous contractions
      rat colon circular muscle, through mechanisms involving in part neural release of
      nitric oxide.

PMID- 15869821
TI  - Impoverishment and patients' "willingness" and "ability" to pay for improving the
      quality of health care in Palestine: an assessment using the contingent valuation
      method.
AB  - This paper examines the impact of impoverishment on patients' preferences with
      respect to improving the quality of health care, by focusing on the sudden
      impoverishment experience that affected the Occupied Palestinian Territory (OPT)
      since the beginning of the second Palestinian Uprising of September 2000. Two
      random samples of patients (352 and 353 individuals, respectively) were
      interviewed about their willingness to pay for improving a set of quality
      attributes in delivery of primary health care, prior and after the occurrence of
      this crisis situation, using a contingent valuation questionnaire. Impoverishment
      did not seem to affect the structure of patients' preferences vis-a-vis some
      essential quality attributes such as "doctor-patient relationship" and "drug
      availability". However, preferences toward "luxury" quality attributes, e.g.,
      "geographical proximity" and "waiting time", suffered from both income-dependent
      and income-independent negative impoverishment effects. We conclude that
      impoverishment might not only affect individuals' availability of resources but
      also the ability of certain groups of patients, notably women, villagers and the
      elderly, to adequately express their preferences toward improving the quality of
      health care delivery. The issue of how willingness to pay results should be
      interpreted in the light of our study for policy implications was discussed. The
      study raises strong doubts about the current policy of introducing patients' cost
      recovery schemes for funding primary health care in the current crisis situation
      of the OPT.

PMID- 15869816
TI  - Expressed sequence tags from the plant trypanosomatid Phytomonas serpens.
AB  - We have generated 2190 expressed sequence tags (ESTs) from a cDNA library of the
      plant trypanosomatid Phytomonas serpens. Upon processing and clustering the set
      of 1893 accepted sequences was reduced to 697 clusters consisting of 452
      singletons and 245 contigs. Functional categories were assigned based on BLAST
      searches against a database of the eukaryotic orthologous groups of proteins
      (KOG). Thirty six percent of the generated sequences showed no hits against the
      KOG database and 39.6% presented similarity to the KOG classes corresponding to
      translation, ribosomal structure and biogenesis. The most populated cluster
      contained 45 ESTs homologous to members of the glucose transporter family. This
      fact can be immediately correlated to the reported Phytomonas dependence on
      anaerobic glycolytic ATP production due to the lack of cytochrome-mediated
      respiratory chain. In this context, not only a number of enzymes of the
      glycolytic pathway were identified but also of the Krebs cycle as well as
      specific components of the respiratory chain. The data here reported, including a
      few hundred unique sequences and the description of tandemly repeated motifs and
      putative transcript stability motifs at untranslated mRNA ends, represent an
      initial approach to overcome the lack of information on the molecular biology of
      this organism.

PMID- 15869820
TI  - Reconstitution of erythroid, megakaryocyte and myeloid hematopoietic support
      function with neutralizing antibodies against IL-4 and TGFbeta1 in long-term bone
      marrow cultures infected with LP-BM5 murine leukemia virus.
AB  - Murine acquired immunodeficiency syndrome (MAIDS) induced by a defective LP-BM5
      murine leukemia virus (MuLV) produces hematopoietic cytopenias similar to HIV in
      patients with AIDS. The pathogenesis of MAIDS induced cytopenias remains obscure;
      however, direct retroviral infection of bone marrow stroma has been implicated to
      play a role. To evaluate the consequential effect of viral infection, primary
      stromal cell cultures were transiently incubated in vitro with LP-BM5 MuLV viral
      supernatant. Reverse transcription polymerase chain reaction (RT-PCR) and
      Southern blot hybridization revealed that defective LP-BM5 MuLV infection
      resulted in elevated levels of IL-4 and TGFbeta1 transcript expression in
      infected stromal cells. The increased expression of both IL-4 and TGFbeta1
      transcripts was associated with enhanced production of corresponding proteins as
      determined by quantitative western blot analyses. Hematopoietic reconstitution
      assays revealed that the hematopoietic support function of stromal cells was
      significantly reduced following transient exposure to LP-BM5 MuLV. The production
      of nonadherent mononuclear cells and the growth of myeloid, megakaryocyte and
      erythroid lineages were all suppressed in infected cultures. Culture supernatant
      conditioned by infected stromal cells demonstrated growth-inhibitory activity for
      hematopoietic progenitor colony formation. This growth-inhibitory activity could
      be significantly abolished by addition of anti-IL-4 and/or anti-TGFbeta1
      neutralizing antibodies to the culture supernatant or directly to the stromal
      cell cultures. This study demonstrates LP-BM5 MuLV increases two known cytokines
      to suppress hematopoiesis implicating viral infection can directly suppress
      hematopoiesis mediated by inhibitors released from marrow stroma.

PMID- 15869822
TI  - Expression and localization of NK(1)R, substance P and CGRP are altered in dorsal
      root ganglia neurons of spontaneously hypertensive rats (SHR).
AB  - The kidneys play a pivotal role in the pathogenesis of essential hypertension
      because of a primary defect in renal hemodynamics and/or tubule hydro-saline
      handling that results in the retention of fluid and electrolytes. Previous
      studies have shown that increasing the renal pelvic pressure increased
      ipsilateral afferent renal nerve activity (ARNA), the ipsilateral renal pelvic
      release of substance P (SP) and the contralateral urinary sodium excretion in
      Wistar--Kyoto rats (WKy). However, spontaneously hypertensive rats (SHR) present
      an impaired renorenal reflex activity associated, partly, with a peripheral
      defect at the level of the sensory receptors in the renal pelvis. Furthermore,
      the renal pelvic administration of SP failed to increase ARNA in most of SHR at
      concentrations that produced marked increases in WKy. Since we have assessed the
      expression and localization of NK(1) receptor (NK(1)R), SP and calcitonin gene
      related peptide (CGRP) in different dorsal root ganglia (DRG) cell subtypes and
      renal pelvis of 7- and 14-week-old SHR. The results of this study show increased
      SP and CGRP expression in the dorsal ganglia root cells of SHR compared to WKy
      rats. Additionally, there was a progressive, significant, age-dependent, decrease
      in NK(1)R expression on the membrane surface in SHR DRG cells and in the renal
      pelvis. In conclusion, the results of the present study suggest that the impaired
      activation of renal sensory neurons in SHR may be related to changes in the
      expression of neuropeptides and/or to a decreased presence of NK(1)R in DRG
      cells. Such abnormalities could contribute to the enhanced sodium retention and
      elevation of blood pressure seen in SHR.

PMID- 15869823
TI  - Nuclear localization of Munc18-1 (p67) in the adult rat brain and PC12 cells.
AB  - Munc18-1, also referred to as p67, co-purifies with Cdk5 and has an important
      role in neurotransmitter release. The role of Munc18-1 for functional
      connectivity of the nervous system was demonstrated by gene knockout experiments
      in mice, wherein accumulation of neurotransmitter and silencing of synaptic
      activity was observed. Our earlier studies have shown that both Munc18-1 and Cdk5
      co-purify and co-localize with cytoskeletal components, implying that apart from
      having a regulatory role in vesicle docking and fusion, Munc18-1 could also
      affect the dynamics of neuronal cytoskeleton. In the present study we have shown
      the presence of Munc18-1 in nuclear rich fraction from rat brain and confirmed
      the nuclear localization of this protein in PC12 cells and adult rat brain
      neurons by immunofluorescence and immunoelectron microscopy. We also demonstrate
      the binding of Munc18-1 to double stranded (ds) DNA. The ability of Munc18-1 to
      bind dsDNA, albeit the lack of DNA binding domains, suggests that the binding may
      be mediated through protein-protein interaction through some other DNA-binding
      proteins. The presence of both nuclear import and export signals in Munc18-1
      primary structure corroborates its nuclear localization and makes it a putative
      shuttle protein between nuclear and cytoplasmic compartments, the precise
      physiological relevance of which needs to be elucidated.

PMID- 15869824
TI  - Blueberry supplemented diet reverses age-related decline in hippocampal HSP70
      neuroprotection.
AB  - Dietary supplementation with antioxidant rich foods can decrease the level of
      oxidative stress in brain regions and can ameliorate age-related deficits in
      neuronal and behavioral functions. We examined whether short-term supplementation
      with blueberries might enhance the brain's ability to generate a heat shock
      protein 70 (HSP70) mediated neuroprotective response to stress. Hippocampal (HC)
      regions from young and old rats fed either a control or a supplemented diet for
      10 weeks were subjected to an in vitro inflammatory challenge (LPS) and then
      examined for levels of HSP70 at various times post LPS (30, 90 and 240 min).
      While baseline levels of HSP70 did not differ among the various groups compared
      to young control diet rats, increases in HSP70 protein levels in response to an
      in vitro LPS challenge were significantly less in old as compared to young
      control diet rats at the 30, 90 and 240 min time points. However, it appeared
      that the blueberry diet completely restored the HSP70 response to LPS in the old
      rats at the 90 and 240 min times. This suggests that a short-term blueberry (BB)
      intervention may result in improved HSP70-mediated protection against a number of
      neurodegenerative processes in the brain. Results are discussed in terms of the
      multiplicity of the effects of the BB supplementation which appear to range from
      antioxidant/anti-inflammatory activity to signaling.

PMID- 15869825
TI  - [Role of referral and practical evaluation in medical decisions].

PMID- 15869826
TI  - [Investigation in the medical faculty: what is the role of the apprentice
      internist in medical decisions regarding the future of medicine?].

PMID- 15869827
TI  - [Neurological manifestations in Sjogren syndrome].
AB  - PURPOSE: To describe clinical and physiopathological aspects of neurological
      involvement in neurological Sjogren syndrome (SS) and to overview biological
      markers and therapeutical aspects. CURRENT KNOWLEDGE AND KEY POINTS: Neurological
      complications during SS may occur between 8.5 and 70%. Peripheral nervous system
      (PNS) involvement is well none but data concerning central nervous system (CNS)
      symptoms have been rarely described. In the present study we detail more
      precisely the heterogeneity of the neurological manifestation in SS. Recently new
      biological of SS such as alpha-fodrin antibodies have been described but there
      interest remain controversial. Furthermore, therapeutical data are scarce and
      there is to date no consensual guidelines for the therapeutical approach.
      PERSPECTIVE: Recent data concerning neurological involvement in SS confirm the
      heterogeneity of clinical presentations that may mimic stroke or multiple
      sclerosis. They underline the need for new biological markers. Furthermore,
      multicentric, randomized trials should be assessed in order to give us some
      therapeutical guidelines.

PMID- 15869828
TI  - Cardioprotective effects of Ilex paraguariensis extract: evidence for a nitric
      oxide-dependent mechanism.
AB  - AIM: To examine the effects of an Ilex paraguariensis (Ip) extract on
      postischemic alterations derived from 20 min of global ischemia and 30 min of
      reperfusion. METHODS: Isolated rat hearts were treated 10 min before ischemia and
      the first 10 min of reperfusion with Ip 30 microg/ml. In other hearts,
      chelerythrine (1 microM), a protein kinase C blocker, or l(G)-nitro l-arginine
      methyl ester (l-NAME), a nitric oxide synthase inhibitor, were administered prior
      to Ip infusion. Left ventricular developed pressure (LVDP), +dP/dt(max), 
      dP/dt(max), and left ventricular end diastolic pressure (LVEDP) were used to
      assess myocardial function. Thiobarbituric acid reactive substances (TBARS) were
      measured. RESULTS: Ip treatment produced an improvement of postichemic recovery
      (LVDP=96+/-8%; +dP/dt(max)=95+/-10%; -dP/dt(max)=90+/-12% vs. 57+/-6%, 53+/-6%
      and 57+/-8%, respectively, in untreated hearts) and an attenuation of the
      increase of LVEDP and TBARS content. Chelerythrine did not modify and l-NAME
      abolished the protection induced by Ip. CONCLUSIONS: These data are the first
      demonstration that Ip extract attenuates the myocardial dysfunction provoked by
      ischemia and reperfusion and that this cardioprotection involves a diminution of
      oxidative damage through a nitric oxide-dependent mechanism.

PMID- 15869829
TI  - A prognostic estimation of the area contaminated with alpha-emitting transuranium
      isotopes in Belarus following the Chernobyl accident.
AB  - As a result of the Chernobyl accident, some regions of Belarus have been
      contaminated with the plutonium isotopes (238,239,240,241)Pu. Considering the
      importance of the environmental impact of the alpha-emitting radionuclides we
      have carried out a prognostic estimation of the area contaminated with
      (238,239,240)Pu and (241)Am (the latter being a decay product of (241)Pu) in
      Belarus. The calculations were made using measurements of (238,239,240)Pu
      activity concentrations in soil samples from about 600 settlements in the
      affected region, together with the estimated activity ratio
      A((241)Am)/A((238,239,240)Pu). The area contaminated with alpha-emitting
      transuranium isotopes predicted for the year 2006 has been compared with that
      estimated for 1986. The results show that by 2006, the area of inhabited
      districts where contamination with (238,239,240)Pu and (241)Am exceeds the
      threshold level of 740 Bq/m(2), will be 3.7 times larger, reaching approximately
      3.5 x10(3)km(2). Of this, almost 20% will have a contamination level of 1850-
      3700 Bq/m(2).

PMID- 15869830
TI  - Impacts of lawn-care pesticides on aquatic ecosystems in relation to property
      value.
AB  - To determine the potential impacts of lawn-care pesticides on aquatic ecosystems,
      the macroinvertebrate communities of six streams were assessed using a
      multimetric approach. Four streams flowed through residential neighborhoods of
      Peachtree City, GA, USA, with differing mean property values and two reference
      streams were outside the city limits. A series of correlation analyses were
      conducted comparing stream rank from water quality and physical stream
      parameters, habitat assessments, benthic macroinvertebrate metric, pesticide
      toxicity and metal toxicity data to determine relationships among these
      parameters. Significant correlations were detected between individual analyses of
      stream rank for pesticide toxicity, specific conductance, turbidity, temperature
      and dissolved oxygen with benthic macroinvertebrate metrics.

PMID- 15869831
TI  - Analyses of neurobehavioral screening data: benchmark dose estimation.
AB  - Zhu et al. (Zhu, Y., Wessel, M., Liu, T., Moser, V.C., 2005. Analyses of
      neurobehavioral screening data: dose-time-response modeling of continuous
      outcomes. Regul. Toxicol. Pharmacol. 41, 240-255) have recently applied dose-time
      response models to longitudinal or time-course neurotoxicity data, and have
      illustrated the modeling process using continuous data from a functional
      observational battery (FOB). Following the work of these authors, the purpose of
      this paper is to show that the benchmark dose (BMD) method for single time point
      dose-response data can be generalized and applied to longitudinal data such as
      those generated in neurotoxicity studies. We propose a statistical procedure
      called bootstrap method for computing the lower confidence limits for the BMD. We
      demonstrate the method using three previously published FOB datasets of
      triethyltin (Moser, V.C., Becking, G.C., Cuomo, V., Frantik, E., Kulig, B.,
      MacPhail, R.C., Tilson, H.A., Winneke, G., Brightwell, W.S., DeSalvia, M.A.,
      Gill, M.W., Haggerty, G.C., Hornychova, M., Lammers, J., Larsson, J., McDaniel,
      K.L., Nelson, B.K., Ostergaard, G., 1997a. The IPCS study on neurobehavioral
      screening methods: results of chemical testing. Neurotoxicology 18, 969-1056.)
      and the models of Zhu et al. (Zhu, Y., Wessel, M., Liu, T., Moser, V.C., 2005.
      Analyses of neurobehavioral screening data: dose-time-response modeling of
      continuous outcomes. Regul. Toxicol. Pharmacol. 41, 240-255).

PMID- 15869832
TI  - Health effects classification and its role in the derivation of minimal risk
      levels: hepatic effects.
AB  - The Agency for Toxic Substances and Disease Registry (ATSDR) derives health based
      guidance values called minimal risk levels (MRLs) to assist with assessment of
      risks posed by exposures to hazardous chemicals. Current MRLs are posted on
      ATSDR's web site (www.atsdr.cdc.gov). From the total 326 MRLs currently posted,
      79 MRLs are based on hepatic endpoints. The paper reports on endpoints used for
      the derivation of these MRLs and the use of uncertainty factors. It also
      describes the ranking of effects into less serious and serious categories as
      described in ATSDR's Guidance for Developing Toxicological Profiles.

PMID- 15869833
TI  - Gender, religious involvement, and HIV/AIDS prevention in Mozambique.
AB  - Using survey and semi-structured interview data collected in various religious
      congregations in urban and rural areas of Mozambique, this study analyzes how
      gender differences in perceptions of HIV/AIDS and preventive behavior are
      mediated by religious involvement. Logistic regression is employed to examine the
      effects of gender and of the interactions between gender and type of denomination
      -"mainline" (Catholic and Presbyterian) or "healing" (Assembly of God, Zionist,
      and Apostolic)--on female and male members' exposure to HIV/AIDS-related
      prevention messages, knowledge and perception of risks, and practice of
      prevention. The analysis detects women's disadvantage on several measures of
      knowledge and prevention but also suggests that gender differences are less
      pronounced among members of "mainline" churches. The semi-structured interview
      data further highlight how gender differences are shaped in different religious
      environments. Although the potential of faith-based institutions in combating the
      HIV/AIDS pandemic is undeniable, policy-makers need to heed important differences
      among these institutions when devising ways to harness this potential.

PMID- 15869834
TI  - Alcohol dependence and depression among heavy drinkers in Canada.
AB  - This article describes the prevalence of heavy drinking among the Canadian
      population and the prevalence of alcohol dependence among heavy drinkers aged 18
      or older. It also examines the association of depression to alcohol dependence
      among the latter group and the correlates of depression and alcohol dependence
      comorbidity. The data are from a national representative sample of the Canadian
      population in 2000/01. One in five current drinkers aged 18 or older was
      classified as a regular heavy drinker. This constituted a significant increase of
      approximately 2% in the prevalence of heavy drinking from 1996/97 to 2000/01 in
      Canada (p<0.001). Although men were more likely to be regular heavy drinkers
      (29.0%) than women (11.1%), male and female heavy drinkers were about equally as
      likely to be classified as alcohol dependent (11.6% and 11.1%, respectively).
      While the prevalence of alcohol dependence among men has remained stable, it has
      decreased by almost 4% among women (p<0.05). Among persons who have experienced a
      depressive episode in the year prior to their 2000/01 interview, the prevalence
      of alcohol dependence was estimated at 32.3% while it was 9.5% for persons
      without depression. When several indicators believed to be risk factors for
      alcohol dependence including personal characteristics, psychosocial factors,
      lifestyle behaviours and physical health were included in the logistic regression
      models, the marked difference in alcohol dependence among depressed and non
      depressed heavy drinkers remained. The former had 3.6 times the odds of being
      classified as alcohol dependent compared to the latter (CI=2.9, 4.3). When the
      same personal, psychosocial, lifestyle and physical health measures were used to
      explain comorbidity of depression and alcohol dependence, perceived stress was
      the only factor that was consistently associated with comorbidity among both men
      and women.

PMID- 15869835
TI  - Economic valuation of informal care: the conjoint measurement method applied to
      informal caregiving.
AB  - This paper reports the results of the application of the conjoint measurement
      method (CM) to determine a monetary value of informal care. Compared to the
      normally recommended valuation methods, like the opportunity cost method and
      proxy good method, CM is probably better able to capture the heterogeneity of
      informal care. We developed a survey in which informal caregivers were asked to
      rate four different hypothetical informal caregiving situations, which differed
      with respect to care hours, care tasks and monetary compensation. Data were
      obtained from postal surveys. A total of 135 pairs of informal caregivers and
      care recipients with rheumatoid arthritis (RA) from the Netherlands returned a
      completed survey and were used in the analysis. Informal caregivers require an
      extra compensation of 1.00 euro per hour for providing one additional hour of the
      same informal care task (meaning that from the seventh to the eighth hour, they
      require 8 euro). For providing two extra hours of care, they require 2.00 euro
      compensation per hour. The relative valuation of informal care tasks is very
      diverse. Respondents require a compensation of 13.43 euro per hour for switching
      from providing light housework to personal care and 0.56 euro per hour for
      switching from providing personal care to heavy housework. Though CM is sometimes
      regarded as cognitively complex, 70% of the respondents were able and willing to
      evaluate the hypothetical caregiving scenarios. Elderly respondents especially
      had more difficulty with the method. In sum, CM is seen as a promising
      alternative for existing methods to determine a monetary value of informal care.
      The presented valuations of informal care can be incorporated in the numerator of
      a cost-effectiveness ratio in economic evaluations of health care.

PMID- 15869836
TI  - Alcoholic myopathy: lack of effect of zinc supplementation.
AB  - A chronic form of myopathy has been described in alcoholics, characterized by
      atrophy of type II fibers, due both to reduced protein synthesis and increased
      protein breakdown. Increased production of reactive oxygen species could probably
      play a role in increased protein breakdown. In addition, treatment with zinc
      might be beneficial, since it acts as a cofactor of several enzymes involved in
      the synthesis of proteins and antioxidants as copper-zinc-superoxidedismutase
      (SOD) and selenium dependent glutathione peroxidase (GPX). Based on these facts,
      we analyze the relative and combined effects of ethanol, protein malnutrition and
      treatment with zinc, 227 mg/l in form of zinc sulphate, on muscle changes in 8
      groups of adult Sprague-Dawley rats fed following the Lieber-de Carli model
      during 5 weeks. We also study the association between muscle histological changes
      and the activity of GPX, SOD and lipid peroxidation products (MDA), with hormones
      such as IGF-1, and with trace elements involved in antioxidant systems and/or in
      lipid peroxidation, such as selenium, copper, zinc, and iron. We found type IIa
      and IIb fiber atrophy in the alcoholic animals, especially in the low-protein fed
      ones. This effect was mainly due to protein deficiency. Zinc played no role at
      all. Muscle iron increased in ethanol, low protein fed rats, either with or
      without zinc, and was directly related with muscle MDA levels, which in turn were
      related with muscle atrophy, as was also found for serum IGF-1 levels. Ethanol
      was the main responsible for all these changes, although protein undernutrition
      also played an independent role in MDA levels. A positive interaction between
      ethanol and protein deficiency on serum IGF-1 was also detected. These results
      suggest that both protein deficiency and ethanol contribute to muscle atrophy
      observed in alcoholized rats; this atrophy is associated with increased lipid
      peroxidation and muscle iron overload. Treatment with zinc sulphate confers no
      benefit.

PMID- 15869838
TI  - Acute and short-term insulin-induced molecular adaptations of GLUT2 gene
      expression in the renal cortex of diabetic rats.
AB  - Increased GLUT2 gene expression in the renal proximal tubule of diabetic rats is
      an adaptive condition, which may be important in the diabetic nephropathy
      development. We investigated the effects of insulin treatment upon the renal
      GLUT2 overexpression of diabetic rats. Acute treatment, surprisingly, induced a
      rapid further increase in GLUT2 mRNA content. Twelve hours after insulin
      injection, GLUT2 mRNA was twice the value of saline-injected rats (P<0.001), when
      GLUT2 protein remained unchanged. In response to short-term treatment, both GLUT2
      mRNA and protein were increased in 1-day treated rats (P<0.05 versus saline
      injected), decreasing after that, and reaching, within 6 days, values close to
      those of non-diabetic rats. Concluding, insulin treatment induced: initially, an
      additional upregulation of GLUT2 gene expression, involving posttranscriptional
      modulation; thereafter, downregulation of GLUT2 expression, which returns to non
      diabetic levels. The former may be related to increased insulin concentration,
      the latter may be due to glycemic control.

PMID- 15869837
TI  - Lipopolysaccharide treatment downregulates the expression of the pregnane X
      receptor, cyp3a11 and mdr1a genes in mouse placenta.
AB  - The cytochrome P450 3A (CYP3A) is a member of the cytochrome P450 monooxygenase
      superfamily. The multidrug resistance 1 (MDR1) gene belongs to the ATP-binding
      cassette (ABC) family. Pregnane X receptor (PXR) is a nuclear receptor that
      regulates its target gene transcription in a ligand-dependent manner.
      Lipopolysaccharide (LPS)-induced downregulation of PXR, CYP3A and MDR1 in liver
      has been demonstrated in a series of studies. However, it is not clear whether
      LPS represses the expression of PXR, CYP3A and MDR1 in placenta. In the present
      study, we investigated the effects of LPS on the expression of PXR, cyp3a11 and
      mdr1a in mouse placenta. Pregnant ICR mice were injected intraperitoneally with
      different doses of LPS (0.1-0.5 mg/kg) on gestational day (gd) 17. Placental PXR,
      cyp3a11 and mdr1a mRNA levels were determined at 12 h after LPS treatment using
      RT-PCR. Results showed that LPS significantly downregulated PXR, cyp3a11 and
      mdr1a mRNA levels in a dose-dependent manner. LPS-induced downregulation of PXR,
      cyp3a11 and mdr1a mRNA in placenta was significantly attenuated after pregnant
      mice were pre- and post-treated with alpha-phenyl-N-t-butylnitrone (PBN), a free
      radical spin trapping agent. Additional experiments revealed that LPS increased
      lipid peroxidation and proinflammatory cytokine expressions in mouse placenta,
      all of which were also attenuated by PBN. Furthermore, LPS-induced downregulation
      of PXR, cyp3a11 and mdr1a mRNA in mouse placenta was prevented by N
      acetylcysteine (NAC). NAC also inhibited LPS-initiated lipid peroxidation, GSH
      depletion and proinflammatory cytokine expressions in mouse placenta. These
      results indicated that LPS downregulates placental PXR, cyp3a11 and mdr1a mRNA
      expressions. Reactive oxygen species (ROS) may be involved in LPS-induced
      downregulation of PXR, cyp3a11 and mdr1a in mouse placenta.

PMID- 15869839
TI  - Ovariectomy increases Na+, K+-ATPase, acetylcholinesterase and catalase in rat
      hippocampus.
AB  - In the present work we investigated the effect of ovariectomy on Na+, K+-ATPase
      and acetylcholinesterase (AChE) activities in rat hippocampus. We also studied
      some parameters of oxidative stress, namely total radical-trapping antioxidant
      potential (TRAP), thiobarbituric acid-reactive substances (TBA-RS), as well as
      the antioxidant enzyme activities superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GSH-Px) activities. Our hypothesis is that ovariectomy
      might cause alterations in essential enzyme activities necessary to brain normal
      functioning and that these chances could be caused by oxidative stress. Female
      adult Wistar rats were divided into three groups: (1) naive (control); (2) sham
      operated; and (3) ovariectomized. Thirty days after ovariectomy rats were
      sacrificed. Results showed that rats subjected to ovariectomy presented a
      significant increase in Na+, K+-ATPase, AChE and CAT activities, but did not
      change the oxidative stress parameters studied when compared to sham or naive
      rats. Since ovariectomy mimics postmenopausal changes, our findings showing
      alteration in the activities of brain Na+, K+-ATPase, AChE and CAT may be related
      to problems in postmenopausal women.

PMID- 15869840
TI  - Is there a difference in risk factors for single and multiple symptomatic lesions
      in small vessel disease? What is the difference between one and plenty-
      experience from 201 Serbian patients.
AB  - OBJECTIVES/PURPOSES: Small vessel disease (SVD) is associated with traditional
      vascular risk factors (RF). The aim of our study was to determine whether
      different SVD types, single lacunar infarction (LI) and multiple LI (MLI) with or
      without white matter lesions (WML), have different RF profiles. PATIENTS AND
      METHODS: Forty RF parameters were analysed in 201 consecutive patients with
      magnetic resonance imaging finding of SVD. RESULTS: History of arterial
      hypertension, higher systolic and mean blood pressure (BP) but also hypotension,
      and higher plasma homocysteine levels were more frequent in MLI compared to
      single LI patients (p<0.05). Patients with one LI were younger, more frequently
      had clinically evident stroke and family history of cardiovascular disease (CVD)
      (p<0.05). Significant difference between groups was found only in these RF,
      indicating that similar pathological processes led to both types of SVD.
      CONCLUSION: Positive correlation with age and family history of CVD necessitates
      further analyses of other factors, predominantly genetic, as the key to the
      answer why patients develop different lesions in SVD.

PMID- 15869841
TI  - Kinetics of gas-liquid reaction between NO and Co(NH3)6(2+).
AB  - Wet ammonia desulphurization process can be retrofitted for combined removal of
      SO2 and NO from the flue gas by adding soluble cobalt(II) salts into the aqueous
      ammonia solutions. The Co(NH3)6(2+) formed by ammonia binding with Co2+ is the
      active constituent of scrubbing NO from the flue gas streams. A stirred vessel
      with a plane gas-liquid interface was used to measure the chemical absorption
      rates of nitric oxide into the Co(NH3)6(2+) solution under anaerobic and aerobic
      conditions separately. The experiments manifest that the nitric oxide absorption
      reaction can be regarded as instantaneous when nitric oxide concentration levels
      are parts per million ranges. The gas-liquid reaction becomes gas film
      controlling as Co(NH3)6(2+) concentration exceeds 0.02 mol/l. The NO absorption
      rate is proportional to the nitric oxide inlet concentration. Oxygen in the gas
      phase is favorable to the absorption of nitric oxide. But it is of little
      significance to increase the oxygen concentration above 5.2%. The NO absorption
      rate decreases with temperature. The kinetic equation of NO absorption into the
      Co(NH3)6(2+) solution under aerobic condition can be written as.

PMID- 15869842
TI  - Experimental alveolar echinococcosis in pigs, lesion development and serological
      follow up.
AB  - Liver lesions were found in 6/6 pigs 7 months after oral inoculation with 5000 or
      35,000 Echinococcus multilocularis eggs. However, lesion morphology differed
      considerably among the animals. The largest lesions (3-8mm in diameter) were
      found in a single pig and smaller lesions (1.5-3mm) in three pigs. These lesions
      were clearly circumscribed and had pronounced central necroses and dystrophic
      calcifications. In contrast, most of the smallest (usually <1.5mm in diameter)
      found in two other pigs, had small compact fibrotic areas and blurred borders
      with obvious fibrous infiltrations into the interlobular tissues. E.
      multilocularis specific DNA was detected by PCR in all lesion types, but
      metacestode viability, as assessed by in vivo intraperitoneal inoculations in
      jirds, could not be demonstrated. Within 1 month post inoculation, all pigs
      developed specific IgG antibody responses against a battery of different antigens
      (metacestode, cyst fluid, and protoscoleces-derived native E. multilocularis and
      E. granulosus antigens, affinity purified Em2G11 antigen, antigen B, recombinant
      Em II/3-10 antigen). Two different reaction patterns were recorded. In the two
      pigs with the small lesions, pronounced reactions against all crude antigens with
      peaks 3-5 months p.i. and clearly elevated levels until the end of the experiment
      were noted. In all other pigs, antibody reactions remained low in all cases. In
      conclusion, we demonstrated two types of E. multilocularis metacestode
      development in pigs with distinct immunological response patterns.

PMID- 15869843
TI  - Purification of a lectin from the marine red alga Gracilaria ornata and its
      effect on the development of the cowpea weevil Callosobruchus maculatus
      (Coleoptera: Bruchidae).
AB  - A lectin from the marine red alga Gracilaria ornata (Gracilariaceae, Rodophyta)
      was purified and characterized. The purification procedure consisted of
      extracting soluble proteins in 0.025 M Tris-HCl buffer, pH 7.5, followed by
      ammonium sulfate precipitation (70% saturation), ion exchange chromatography on
      DEAE-cellulose and affinity chromatography on mucin-Sepharose 4B. The purified G.
      ornata lectin (GOL) showed a single protein band with an apparent molecular mass
      of 17 kDa when submitted to SDS-polyacrylamide gel electrophoresis under reducing
      conditions. The native molecular mass of GOL determined by gel filtration on a
      Sephadex G-100 column was 17.4 kDa and its carbohydrate content was estimated to
      be 2.9%. Therefore, GOL is a monomeric glycoprotein. The purified lectin
      agglutinated trypsin-treated erythrocytes from rabbit and chicken but not from
      human. Its activity was not inhibited by any of the mono- and disaccharides
      tested but by the complex glycoproteins porcine stomach mucin, lactotransferrin,
      asialofetuin and bovine and porcine thyroglobulins. Isoelectric focusing showed
      that GOL is an acidic protein with a pI of 5.4 with analysis of its amino acid
      composition revealing high contents of Asx, Glx, Ser, Glu, Ala and Cys. When
      incorporated in artificial seeds, GOL significantly affected the development of
      Callosobruchus maculatus larvae, indicating the possibility of using this lectin
      in a biotechnological strategy for insect management of stored cowpea seeds.

PMID- 15869844
TI  - Cigarette smoking topography in smokers with schizophrenia and matched non
      psychiatric controls.
AB  - Smoking is highly prevalent among people with schizophrenia, and little is known
      about factors that affect smoking in these patients. One basic question is
      whether smoking behavior differs for smokers with schizophrenia compared to
      equally nicotine-dependent smokers who do not have a major mental illness. In
      this study, 20 smokers with schizophrenia or schizoaffective disorder (SCZ) and
      20 non-psychiatric smokers (CON) underwent smoking topography assessments. The
      groups were matched on age, gender, daily smoking rate, years of regular smoking
      and nicotine dependence rating. Results indicate that, compared to the CON
      participants, the SCZ participants smoked significantly more total puffs (SCZ:
      58.5 +/- 48.3; CON: 21.3 +/- 9.4) and puffs per cigarette (SCZ: 12.3 +/- 6.0;
      CON: 8.9 +/- 2.3) and had shorter inter-puff intervals (SCZ: 21.9 +/- 9.7 s; CON:
      42.0 +/- 21.5 s), larger total cigarette puff volumes (SCZ: 583 +/- 169 ml; CON:
      429 +/- 159 ml) and higher carbon monoxide boosts (SCZ: 3.8+/-5.4 ppm; CON: 1.0
      +/- 2.5 ppm). Test-retest reliabilities were good to excellent for most smoking
      measures in both groups. These findings suggest that smokers with schizophrenia
      smoke more intensely than matched non-psychiatric smokers and that their smoking
      behavior is reliable when assessed under laboratory conditions.

PMID- 15869845
TI  - Development and validation of a brief instrument for routine outcome monitoring
      in opioid maintenance pharmacotherapy services: the brief treatment outcome
      measure (BTOM).
AB  - AIM: To develop a brief, multi-dimensional instrument for routine, on-going
      treatment outcome monitoring in alcohol and other drug (AOD) services in
      Australia and examine the underlying psychometric properties. This study focuses
      on opioid maintenance pharmacotherapy (OMP) services. DESIGN: Researcher
      administered test-retest interviews and clinician administered interviews.
      SETTING: The test-retest interviews took place in two private and two public OMP
      clinics in Sydney, Australia. The clinician-administered interviews took place in
      37 metropolitan, rural and prison OMP services in New South Wales, Australia.
      PARTICIPANTS: One hundred and sixty current OMP clients for the test-retest
      interviews and 2004 clients commencing OMP treatment for the clinician
      administered interviews. MEASURES: Thirty-two items across the domains of
      dependence, blood-borne virus exposure risk, drug use, health/psychological
      functioning and social functioning. FINDINGS: The internal reliability of the
      brief treatment outcome measure (BTOM) is satisfactory. Retest reliabilities for
      the scales and drug use scores are good to excellent indicating their consistency
      with multiple measurements across time and different interviewers and concurrent
      validation of BTOM scales with analogous scales from similar instruments yielded
      acceptable agreement. Average completion times of the BTOM were 14.5 min, when
      administered in a research context and 21 min in a clinical context. CONCLUSIONS:
      A brief, valid and reliable questionnaire has been developed for monitoring
      treatment outcome over the range of OMP services. The BTOM contains a core set of
      outcome measures, which can be easily adapted for integration into routine
      clinical practice across the range of AOD services.

PMID- 15869846
TI  - Patient perspectives on methadone maintenance treatment in the Valencia Region:
      dose adjustment, participation in dosage regulation, and satisfaction with
      treatment.
AB  - Desired adjustment of methadone dose, perceived participation in dosage
      regulation, and satisfaction with methadone treatment centres were assessed in a
      sample of opioid-dependent patients from the Valencia Region (eastern Spain). An
      independent interviewer asked 278 consecutively arriving patients to answer the
      survey, and 165 (59.4%) completed it. Adjustment of methadone dose was assessed
      with a -10 to +10 visual analogue scale (VAS-MD); participation in methadone dose
      regulation, with specific questions; and patient satisfaction, with the Verona
      Service Satisfaction Scale for methadone treatment (VSSS-MT). The methadone dose
      (mg/d) prescribed by physicians was (mean+/-S.D.) 68.0+/-30.4. Participants
      scored -1.0+/-4.7 on the VAS-MD, indicating a significant downward desired
      adjustment of methadone dose (95% CI of -1.73 to -0.30). Of the patients
      surveyed, approximately one-third were, overall, content with their participation
      in methadone dose regulation. Overall, participants felt slightly satisfied (VSSS
      MT=3.5+/-0.6) with the centres. Patients treated with a methadone dose of < 60
      mg/d felt more satisfied than those treated with 60-100 mg/d. Information about
      dose changes was the only continuous methadone dose variable related with
      satisfaction that was found in a multiple regression analysis, which accounted
      for only 2.0% of the variance in VSSS-MT overall scores. In conclusion, patients'
      opinions on methadone dose and patient satisfaction are only very weakly related
      when methadone treatment is implemented as in the Valencia Region.

PMID- 15869847
TI  - Isolation and characterization of a plasmid DNA from periodontopathogenic
      bacterium, Eikenella corrodens 1073, which affects pilus formation and colony
      morphology.
AB  - Eikenella corrodens (Ec) is one of a group of periodontopathogenic bacteria. A
      plasmid DNA (8.7 kb) isolated from Ec 1073 was designated pMU1. Agarose gel
      electrophoresis and Southern analysis suggested that pMU1-like plasmids were
      carried in 2 Ec strains, including 1073, with higher hemagglutination (HA)
      activity than other strains. We determined the nucleotide sequence of this
      plasmid and identified 7 ORFs. A homology search revealed that 4 ORFs of pMU1
      were homologous to ORFs in pJTPS1, found in a spontaneous avirulent mutant of the
      phytopathogenic bacterium, Ralstonia solanacearum. pJTPS1 is a putative
      hypovirulent plasmid, which is thought to control the virulence of R.
      solanacearum. We also found the ORF to be homologous to the recombinase specific
      to the type IV pilin gene. We introduced a part of pMU1 into the Ec 23834 strain,
      which has a pilus structure on its cell surface and forms corroding colonies on
      solid medium. No pilus structure was observed on the surface of transformants,
      most of which formed non-corroding colonies. When such transformants (or Ec 1073)
      were cured of pMU1 with acridine orange, they remained non-foliated and non
      corroding. The results suggest that pMU1 might irreversibly affect pilus
      formation and colony morphology, and might be involved in the pathogenicity and
      virulence of Ec.

PMID- 15869848
TI  - Management of hypotension and circulatory assessment on NICU.

PMID- 15869849
TI  - Fertility and hatchability of eggs laid in the pullet-to-breeder transition
      period and in the initial production period.
AB  - The initial eggs produced by broiler breeder hens are relatively small compared
      with later in the production cycle. An evaluation of indices related to
      hatchability is required when these eggs are to be used for the production of
      broiler chicks. Two experiments were conducted to evaluate characteristics
      related to the hatchability of eggs from pullet-to-breeder transition phase, at
      25 and 27 weeks of age, and from the peak of production period and five weeks
      later, at 32 and 37 weeks of age. Eggs from birds 25 weeks had a lesser fertility
      in Experiment 1. Mortality occurred unevenly in early (1-5 days), middle (6-17
      days) and late (18-21 days) incubation, and greater mortality was observed after
      the internal membrane was ruptured. The younger the hen, the lighter the egg,
      chick, and shell, and the longer the time required to complete the hatching
      process. In Experiment 2, greater mortalities were observed at the early period
      (1-5 days) and after "pipping" of the internal and external membranes. Embryos
      from heavy eggs of breeder hens 37 weeks of age took less time to complete the
      hatching process. Results indicated the larger the egg, the heavier the chick and
      shell, and the lesser the shell percentage. As breeder age advanced,
      characteristics related to egg fertility and hatchability improved.

PMID- 15869850
TI  - Effect of small doses of naloxone on sexual exhaustion in White New Zealand male
      rabbits.
AB  - The objective of the present study was to determine the effect of small doses of
      naloxone on sexual exhaustion in White New Zealand male rabbits. Twelve young and
      12 adult male rabbits 6-12 months old and 14-20 months of age, respectively, were
      selected from a commercial farm. Each male rabbit was housed individually in
      galvanized cages (90 cm x 60 cm x 40 cm). The rabbits were housed in an open shed
      exposed to natural photoperiod (12 L 12 D, 19 degrees N). Daily temperature
      fluctuated through the year from 28 to 16 degrees C. Humidity was 45+/-5%. Water
      and food (rabbit chow PMI) was supplied ad libitum. After sexual behaviour for
      each studied group was established, the males were given a 6-day rest, and 3 days
      before next trial, six males of each group (treated) received a subcutaneous
      implant of 8 mg of naloxone in a crystalline nitrocellulose pellet formulated to
      be completely absorbed in 15 days. The remaining six males were sham-treated
      (control). At the end of the resting period as previously described, the sexual
      behavior of each group was studied and compared using a Mann-Whitney statistical
      U-test. The effect of naloxone on sexual behavior was analyzed with a Wilcoxon
      test for correlated samples. With regard to sexual activity between young and
      adult rabbits, it was observed that there was a significant difference between
      groups (P=0.00275, Z=2.8823, adjusted Z=2.99.43) showing that younger rabbits
      mounted/ejaculated from 9 to 10 females compared with 6 to 8 mounted/ejaculated
      by older rabbits. When naloxone was administered to both groups, there was a
      significant difference when comparing sexual behavior before and after
      administration of naloxone (table first and second trial). Young rabbits treated
      with naloxone mounted/ejaculated 11-12 females while older rabbits mounted nine
      females before reaching sexual exhaustion. A significant difference was observed
      when comparing the number of estrous females that were mounted/ejaculated between
      groups. Environmental photoperiod and temperature changes were not considered. It
      was concluded that endogenous opioids are important modulators of behavioral and
      hormonal interactions related to sexual behavior.

PMID- 15869851
TI  - In vitro and in vivo methotrexate disposition in alveolar macrophages: comparison
      of pharmacokinetic parameters of two formulations.
AB  - MTX-liposomes, prepared with a polymerised core (LSP), were administered in
      anaesthetised rats by pulmonary instillation versus free drug. No toxicological
      effects were macroscopically observed. After each time point: 15, 30, 60 and 90
      min, animals were humanely killed and analyses of radio-signal were done. This
      approach allowed recovery of MTX or breakdown products within biological samples.
      Previously, kinetics of MTX cellular uptake was performed to identify the
      cytotoxic concentration of drug formulation for human macrophage. Flow cytometry
      was set-up to characterise liposomal uptake by ex vivo pulmonary macrophage.
      Cells were isolated by bronchioloalveolar washes from animals. Results have shown
      clear different pharmacokinetic parameters between free MTX and the liposomal
      form of MTX. Unlike classical liposomes, which are mainly taken up by the
      reticulo-endothelial system, LSP-MTX was not targeted to spleen or kidney. The
      route of administration could be an explanation of this phenomenon. In addition,
      LSP-MTX was more retained by the lung tissue. Moreover, free form of the drug
      reaches easily lymph node. This latest result should be taken into consideration
      for neoplasic disease and more specifically when lymph nodes are a way for
      pulmonary metastasis. Finally, LSP-MTX should be tested in physio-pathological
      model of lung cancer to evaluate the influence of the variation of liposomal
      formulation pharmacokinetic parameters on the drug efficacy.

PMID- 15869852
TI  - A method for screening for various sedative-hypnotics in serum by liquid
      chromatography/single quadrupole mass spectrometry.
AB  - A screening method for the detection of sedative-hypnotics in serum is described.
      The target drugs, which include practically all the sedative-hypnotics
      distributed in Japan, consisted of 5 barbiturates, 30 benzodiazepine-related
      drugs and 11 other sedative-hypnotics (i.e., apronalide, bromisovalum, chloral
      hydrate, triclofos, chlorpromazine, promethazine, diphenhydramine, hydroxyzine,
      zopiclone, zolpidem and tandospirone). Thirty-nine analytes, selected in terms of
      the pharmacokinetics of the target drugs, in human serum were screened using a
      combination of mixed-mode solid-phase extraction and liquid
      chromatography/electrospray-ionization single-quadrupole mass spectrometry. The
      detection limits (non-basic analytes, 1-50 ng/ml; basic analytes, 0.1-5 ng/ml)
      were sufficient to permit the screening of a single therapeutic administration of
      a target drug.

PMID- 15869853
TI  - Oncocytic carcinoma in the submandibular gland: report of a case based on anti
      mitochondrial immunohistochemical observations.
AB  - Oncocytic carcinoma arising in the submandibular gland is a very rare tumor that
      has only previously been reported in nine cases. This paper describes an
      additional case of oncocytic carcinoma in the right submandibular gland. The
      patient was a 55-year-old Japanese male who was presented with a 3 cm right
      submandibular mass. Both radical resection of the tumor and right supraomohyoid
      neck dissection were performed. Histologically, the tumor cells exhibited an
      abundant eosinophilic cytoplasm, which appeared to be finely granular, and
      invaded the surrounding tissues. In addition, perineural invasion was also
      observed. Electron microscopy demonstrated the presence of an abundance
      mitochondria in the cytoplasm of the tumor cells. However, since the fine
      structure of cytoplasm was destroyed by fixation and embedding of the tissue for
      the light microscopy, the cytoplasm of the tumor could not be observed clearly.
      Immunohistochemically, anti-mitochondrial antibody positivity was evident in the
      cytoplasm of the tumor cells. Consequently, we diagnosed the mass as oncocytic
      carcinoma. Usually, electron microscopy is necessary to diagnose oncocytic
      lesions, but the paraffin-embedded tissue was not suitable for electron
      microscopy. Immunohistochemistry using an anti-mitochondrial antibody was found
      to be useful and helpful for the diagnosis of oncocytic lesions.

PMID- 15869854
TI  - Treatment of scattered glass foreign bodies in both the superficial and deep
      neck: a case report.
AB  - There have not been any reports about scattered glass foreign bodies in the neck,
      while injuries of the head and neck region as a result of traffic accidents have
      been frequently reported. We report the case of a 17-year-old male injured in a
      traffic accident, with scattered glass foreign bodies in both the superficial and
      deep neck. A CT scan indicated the existence of numerous glass foreign bodies in
      the various layers of the neck. Most of the foreign bodies were very fine or sand
      like. The wounded skin was keloidal and expected to lead to remarkable facial
      edema of the left side. The foreign bodies and cervical keloidal lesions with
      small pieces of glass were carefully removed, and then reconstruction was
      conducted in stages using tissue expanders. The facial edema was reversed and the
      aesthetic reconstruction satisfied the patient.

PMID- 15869855
TI  - Superior turbinate osteoma: a case report.
AB  - Turbinate osteoma is very rare and only three middle turbinate cases have been
      previously reported in the literature. A case of superior turbinate osteoma has
      never been reported before. This is a report of a 61-year-old female presenting
      superior turbinate osteoma with headaches. The osteoma was resected by endoscopic
      sinus surgery (ESS) and the patient was relieved of headaches.

PMID- 15869856
TI  - Rapid, small-scale determination of organic solvent solubility using a
      thermogravimetric analyzer.
AB  - A rapid gravimetric method for determining drug candidate solubility in organic
      solvents has been developed. The scale, speed, precision, and accuracy of the
      method make it ideal for solubility screening of pharmaceutical compounds during
      early development. The method utilizes a thermogravimetric analyzer to automate
      drying and weighing. Results for model compounds compare favorably with
      literature values.

PMID- 15869857
TI  - Quantitative determination of polymorphic composition in intact compacts by
      parallel-beam X-ray powder diffractometry II. Data correction for analysis of
      phase transformations as a function of pressure.
AB  - An analytical, non-destructive method using parallel-beam transmission powder X
      ray diffractometry (PXRD) is presented for in situ whole compact detection and
      quantification of solid-state phase transformations in powder compacts. Accurate
      quantification of analyte in intact compacts using PXRD requires a mathematical
      correction prior to interpolation of calibration data to account for sample
      differences that result as a function of pressure; namely, compact thickness and
      solid fraction. Chlorpropamide is examined as a model system, selected because of
      its susceptibility to polymorphic transformations when consolidated using
      moderately low pressures. The results indicate that quantification of the
      transformed phase of chlorpropamide without corrections for solid fraction and
      thickness, underestimates the extent of transformation by 2.4%. Although the
      magnitude of the correction for this particular system of polymorphs is small,
      more significant values are expected for other compounds, particularly those with
      sufficient compactibility to allow the formation of low solid fraction
      calibration samples.

PMID- 15869858
TI  - Quantification of bambuterol hydrochloride in a formulated product using solid
      state NMR.
AB  - Carbon-13 NMR spectra of the stable polymorphs of solid bambuterol hydrochloride
      (BHC) and terbutaline sulfate (TBS) are reported and the resonances assigned with
      the aid of solution-state spectra. A protocol is presented for quantification of
      BHC in a formulation in lactose, together with TBS, relative to a reference peak
      from magnesium stearate. This protocol compares the intensity of an aromatic
      signal of BHC with that of the main-chain methylene carbons of the stearate. It
      is shown that the limit of detection (LOD) of BHC in this system under the
      conditions described is 0.5% with an effective limit of quantification (LOQ) of
      1.0%. A calibration plot for the quantification is presented and the various
      factors affecting the accuracy of the measurements are described. No discernible
      differences are found in the spectra of physical mixtures of the components,
      whole tablets, and crushed or ground tablets.

PMID- 15869859
TI  - Ontogenetic development, sexual differentiation, and effects of Aroclor 1254
      exposure on expression of the arylhydrocarbon receptor and of the arylhydrocarbon
      receptor nuclear translocator in the rat hypothalamus.
AB  - Interaction of polychlorinated biphenyls (PCBs) with the aryl hydrocarbon
      receptor (AhR)/nuclear translocator (ARNT) system might interfere with the
      mechanisms controlling the sexual differentiation of the developing hypothalamus.
      The aim of this study was to evaluate the presence of AhR/ARNT in brain cells and
      the developmental profile of their expression in the hypothalamus of male and
      female rats during the perinatal period. Brain accumulation of the main PCB
      congeners after prenatal exposure to Aroclor 1254 and its influence on
      hypothalamic expression of AhR/ARNT was also assessed. The results show that: (a)
      AhR and ARNT are expressed both in neurons and in glia; (b) AhR expression
      progressively increases in the developing hypothalamus particularly in males,
      while ARNT is relatively constant in both sexes; (c) the prenatal administration
      of Aroclor to dams produces a differential accumulation of PCBs, depending on the
      chlorine atom number, and stimulates AhR expression only in the male
      hypothalamus. In conclusion, the developing male hypothalamus might be more
      sensitive to disrupting potential of PCBs.

PMID- 15869860
TI  - Examination of meningocele induced by the antitumor agent DE-310 in rat fetuses.
AB  - The antitumor drug, DE-310, is the slow release form of the camptothecin
      derivative DX-8951. We investigated a toxicological profile of meningoceles in SD
      rat fetuses, whose mothers received intravenous DE-310 at several doses, and the
      time course changes of histology. DE-310 induced a meningocele in the posterior
      fontanelle of live fetuses by the four-time administration of 0.3 mg/(kgday) or
      more during the organogenetic period, or by a single administration of 1.0 mg/kg,
      particularly, between days 7 and 13 of gestation with an incidence of 100%. The
      meningocele was caused by the principal ingredient DX-8951. The earliest
      histological change was focal congestion between the skin and cerebrum, followed
      by the formation of a space covered by thinned epidermis with necrosed basal
      cells, hemorrhage in the surrounding connective tissues, cerebrum and ventricles,
      cavitation of the cerebrum, and incomplete formation of the skull bones and
      subarachnoid space. DE-310 was characterized as preferentially inducing
      meningocele (meningoencephalocele in severe cases) in rat fetuses.

PMID- 15869861
TI  - Prenatal marijuana exposure: effect on child depressive symptoms at ten years of
      age.
AB  - Studies of the consequences of prenatal marijuana use have reported effects
      predominantly on the behavioral and cognitive development of the children.
      Research on other aspects of child neurobehavioral development, such as
      psychiatric symptomatology, has been limited. This study examines the relations
      between prenatal marijuana exposure (PME) and child depressive symptoms at 10
      years of age. Data are from the 10-year follow-up of 633 mother-child dyads who
      participated in the Maternal Health Practices and Child Development Project.
      Maternal prenatal and current substance use, measures of the home environment,
      demographic status, and psychosocial characteristics were ascertained at prenatal
      months four and seven, at delivery, and at age 10. At age 10, the children also
      completed the Children's Depression Inventory (CDI) [M. Kovacs. The Children's
      Depression Inventory, Multi-Health Systems, Inc., North Tonawanda, NY, (1992).],
      a self-report measure of current depressive symptoms. Multivariate regressions
      were used to test trimester-specific effects of marijuana and their associations
      with the CDI total score, while controlling for significant prenatal predictors
      and significant current covariates of childhood depression. PME in the first and
      third trimesters predicted significantly increased levels of depressive symptoms.
      This finding remained significant after controlling for all identified covariates
      from both the prenatal period and the current phase at age 10. These findings
      reflect an association with the level of depressive symptoms rather than a
      diagnosis of a major depressive disorder. Other significant correlates of
      depressive symptoms in the children included maternal education, maternal tobacco
      use (prenatal or current), and the child's composite IQ score. These findings are
      consistent with recent reports that identify specific areas of the brain and
      specific brain functions that are associated with PME.

PMID- 15869862
TI  - Genetic factors in pemphigus.
AB  - Epidemiological studies performed in different ethnic populations and family
      studies, notably based on a partial phenotype of the autoimmune process, indicate
      that genetic factors are involved in the occurrence of pemphigus. However, the
      precise heritability remains uncertain in the absence of twin concordance rate
      studies. Among the different strategies available to identify genetic factors
      participating in autoimmune disease susceptibility, only population studies based
      on case-control design have been performed in pemphigus. These studies
      consistently showed that MHC locus, in particular HLA class II alleles, are
      associated with pemphigus vulgaris and pemphigus foliaceus. Other genes of the
      MHC locus may also participate in disease susceptibility as shown by studies
      using microsatellite markers across different regions of the MHC. It is likely
      that other non-MHC genes are involved in the pathogenesis of pemphigus. In
      particular, involvement of a polymorphic variant of desmoglein 1 gene was shown
      to be associated with pemphigus foliaceus and to interact in an epistatic manner
      with MHC class II genes to contribute to the autoimmune process. Other candidate
      genes to which a role can be assigned in the disease pathogenesis should be
      considered to design case-control or family-based association studies. Genome
      scan studies which require a large number of multiplex families to reach
      statistical power, should also be considered in the endemic form of pemphigus
      foliaceus because of the high number of familial cases.

PMID- 15869863
TI  - Isolation and characterisation of a human monoclonal autoantibody to the islet
      cell autoantigen IA-2.
AB  - A hybridoma secreting a human monoclonal autoantibody to the islet cell
      autoantigen IA-2 was prepared from peripheral lymphocytes of a patient with type
      1 diabetes and Graves' disease using EBV infection followed by fusion with a
      mouse/human hybrid cell line. The monoclonal antibody (M13) is an IgG1/kappa and
      in an immunofluorescence test M13 at 1 microg/mL showed islet cell antibody
      reactivity equivalent to 40 JDF units. M13 IgG bound (35)S-labelled IA-2 (26% at
      100 microg/mL) and (125)I-labelled IA-2 (34% at 100 microg/mL) in an
      immunoprecipitation assay and reacted well with IA-2 in western blotting
      analysis. Amino acids 777-808 in the PTP domain of IA-2 were found to be
      important for M13 binding in an analysis using modified (35)S-labelled IA-2
      proteins. M13 V region genes were from VH1-3, D3-22, JH4b, VKI DPK8/Vd+ and JK3
      genes and showed a high replacement/silent mutation ratio for both the heavy
      (11.0) and the light (6.0) chain genes. Mouse monoclonal antibodies (mMAbs)
      reactive with at least three different epitopes within IA-2 aa 604-686
      corresponding to the juxtamembrane domain were also obtained. F(ab')(2) or Fab
      from the mMAbs inhibited serum IA-2 autoantibody binding to IA-2 in 20/22
      diabetic sera whereas M13 F(ab')(2) caused inhibition in only 6/22 sera. M13 is
      representative of some patient serum IA-2 autoantibodies and as such provides a
      useful tool to study autoimmune responses to IA-2.

PMID- 15869864
TI  - Expression of the NK-1 receptor on islet cells and invading immune cells in the
      non-obese diabetic mouse.
AB  - The underlying mechanistic causes of immune cell infiltration in the islets of
      Langerhans and beta cell failure in the non-obese diabetic (NOD) mouse is still
      to be completely revealed. Substance P (SP) is a substance known to have pro
      inflammatory, endocrine, neuromodulatory and trophic effects, and its preferred
      receptor, the neurokinin receptor 1 (NK-1 R), is reported to be involved in
      extravasation of granulocytes and in inflammation and tissue derangement.
      Therefore, we have investigated the expression of NK-1 R during development of
      insulitis in the NOD mouse. We show that the magnitude of immunoreactivity
      scoring NK-1 R expression in the islets was increased in the 12-week-old NOD
      mouse. Expression of NK-1 R co-localized with expression of glucagon. In line
      with this expression pattern, we did not detect any effect of SP on glucose
      induced insulin release. NK-1 R expression was particularly observed in islet
      cells in association with the clusters of immune cells. Expression of NK-1 R was
      also demonstrated in a fraction of the infiltrating B and T lymphocytes, as well
      as on infiltrating macrophages and dendritic cells. The observations show that
      the level of NK-1 R expression is increased in 12-week-old NOD mice, being
      correlated with the occurrence of islet mononuclear infiltration. Our data
      suggest that SP may act as a chemoattractant, contributing to the pathogenic
      mononuclear infiltration process in the NOD mouse. On the whole, the observations
      suggest that SP and the NK-1 R to certain extents are involved in the changes
      that occur during the development of insulitis in the NOD mouse.

PMID- 15869865
TI  - Midline versus paramidline mandibulotomy: a radiological study.
AB  - Mandibulotomy allows for wide exposure of deep oral cavity and oropharyngeal
      tumors and may be performed medial or lateral to the mental foramen. Medial
      mandibulotomy is divided into midline and paramidline. Midline mandibulotomy
      requires detachment of muscles which may lead to masticatory and swallowing
      problems and could potentially jeopardize the central incisors. Our study
      provides a basis for placement of bone cuts in mandibulotomy. The angles between
      the long axis of the two central incisors, the lateral incisor and canine
      bilaterally were measured in panoramic radiographs of 100 healthy patients. The
      distances between the roots were measured. The angle between the lateral incisor
      and the canine ranged from 1 degrees to 8 degrees compared to 1 degrees -4
      degrees (P<0.001) between the central incisors. The distances between the lateral
      incisor and the canine were 1-6.2mm while the distances between the two central
      incisors ranged from 0.5 to 4.7mm (P<0.05). Although the measurements were taken
      from a younger group of patients compared to the usual age of presentation of
      oropharyngeal cancer, it shows that the paramidline mandibulotomy in which bony
      cuts are performed through a wider gap is the preferred approach.

PMID- 15869866
TI  - Severity of oral mucositis correlates with the response of oral cancer to
      preoperative radiochemotherapy.
AB  - Oral mucositis is a dose-limiting toxic effect of radiotherapy and chemotherapy
      on oral cancer. The purpose of the present study is to assess the relationship
      between tumor response and oral mucositis in preoperative radiochemotherapy for
      oral cancer retrospectively. Fifty-four cases of oral squamous cell carcinoma
      were treated with concurrent radiochemotherapy prior to surgery. When oral
      mucositis was evaluated with the WHO scale, severe oral mucositis (Grades 3 and
      4) developed in 22 cases (41%). A more than 50% reduction in tumor size was
      clinically observed in 38 cases (70%). From histopathological analysis of the
      surgical specimens all tumor cells observed appeared to be non-viable in 16 cases
      (29%). The cases with Grade 1, Grade 2, Grade 3 and Grade 4 oral mucositis
      included 33%, 62%, 85% and 89% of clinical good-response cases and 0%, 24%, 31%
      and 55% of histopathological good-response cases, respectively. This
      retrospective study suggests that severe oral mucositis promises a good response
      of oral squamous cell carcinoma to radiochemotherapy.

PMID- 15869867
TI  - Zonisamide: physician and patient experiences.
AB  - This study evaluates information regarding physician and patient experiences with
      zonisamide obtained from the early access and support for epilepsy (EASE)
      program. Both physicians and patients completed initiation questionnaires
      regarding seizure history and antiepileptic drug (AED) use. Physicians were
      advised to initiate zonisamide at 100 mg/day and titrate either to a clinical
      response or a maximum dosage of 600 mg/day. After > or = 2 months of zonisamide
      therapy, physicians and patients were asked to complete follow-up questionnaires
      that included questions regarding seizure frequency, seizure severity, and
      quality of life. Initiation questionnaires and follow-up questionnaires were
      submitted by 80 physicians for 163 patients. According to these data, seizure
      control, functional status, and other symptoms of epilepsy were improved in 57.4%
      (93/162), 37.1% (59/159), and 30.6% (48/157) of patients, respectively.
      Physicians intended to continue zonisamide therapy in 77.4% (123/159) of
      patients. Ninety-six patients submitted both initiation and follow-up
      questionnaires. Seizure control, seizure severity, and quality of life were
      improved in 53.6% (45/84), 58.8% (50/85), and 62.1% (54/87) of patients,
      respectively. These patients, most of whom were refractory to other AEDs,
      generally had positive experiences with zonisamide.

PMID- 15869869
TI  - Gene expression profiling of pulpal tissue reveals the molecular complexity of
      dental caries.
AB  - High-throughput characterisation of the molecular response of pulpal tissue under
      carious lesions may contribute to improved future diagnosis and treatment. To
      identify genes associated with this process, oligonucleotide microarrays
      containing approximately 15,000 human sequences were screened using pooled total
      RNA isolated from pulpal tissue from both healthy and carious teeth. Data
      analysis identified 445 genes with 2-fold or greater difference in expression
      level, with 85 more abundant in health and 360 more abundant in disease.
      Subsequent gene ontological grouping identified a variety of processes and
      functions potentially activated or down-modulated during caries. Validation of
      microarray results was obtained by a combination of real-time and semi
      quantitative PCR for selected genes, confirming down-regulation of Dentin Matrix
      Protein-1 (DMP-1), SLIT 2, Period-2 (PER 2), Period-3 (PER 3), osteoadherin,
      Glypican-3, Midkine, activin receptor interacting protein-1 (AIP 1), osteoadherin
      and growth hormone receptor (GHR), and up-regulation of Adrenomedullin (ADM),
      Interleukin-11 (IL-11), Bone sialoprotein (BSP), matrix Gla protein (MGP),
      endothelial cell growth factor-1 (ECGF 1), inhibin beta A and orosomucoid-1 (ORM
      1), in diseased pulp. Real-time PCR analyses of ADM and DMP-1 in a panel of
      healthy and carious pulpal tissue and also in immune system cells highlighted the
      heterogeneity of caries and indicated increased expression of ADM in neutrophils
      activated by bacterial products. In contrast, DMP-1 was predominantly expressed
      by cells native to healthy pulpal tissue. This study has greatly extended our
      molecular knowledge of dental tissue disease and identified involvement of genes
      previously unassociated with this process.

PMID- 15869868
TI  - An antibacterial and antiviral peptide produced by Enterococcus mundtii ST4V
      isolated from soya beans.
AB  - Enterococcus mundtii ST4V, isolated from soya beans, produces a 3950Da
      antibacterial peptide active against Gram-positive and Gram-negative bacteria,
      including Enterococcus faecalis, Streptococcus spp., Pseudomonas aeruginosa,
      Klebsiella pneumoniae, Streptococcus pneumoniae and Staphylococcus aureus. The
      peptide also inactivated the herpes simplex viruses HSV-1 (strain F) and HSV-2
      (strain G), a polio virus (PV3, strain Sabin) and a measles virus (strain
      MV/BRAZIL/001/91, an attenuated strain of MV). MV, HSV-1 and HSV-2 were 95.5%
      99.9% inactivated by peptide ST4V at 400 microg/ml. Monkey kidney Vero cells were
      not inactivated, even at four times the level peptide ST4V displayed antiviral
      activity, indicating that the effect was not due to cytotoxicity. Complete
      inactivation or significant reduction in antimicrobial activity was observed
      after treatment of peptide ST4V with Proteinase K, pronase, pepsin and trypsin.
      No change in antimicrobial activity was recorded after treatment with alpha
      amylase, suggesting that peptide ST4V was not glycosylated. This is the first
      description of an antibacterial and antiviral peptide with such broad-spectrum of
      activity, produced by a lactic acid bacterium.

PMID- 15869870
TI  - KIT overexpression and amplification in gastrointestinal stromal tumors (GISTs).
AB  - The tyrosine kinase receptor KIT plays a major role in gastrointestinal stromal
      tumors (GISTs) oncogenesis. Indeed, 95% of GISTs express KIT protein, and about
      70% exhibit activating mutations of the KIT gene. However, little is known about
      KIT overexpression mechanisms in these tumors, and the correlation with KIT
      mutations. GISTs with mutations within exon 11 (n=12) or 9 (n=1) of KIT were
      compared with GISTs without KIT mutations in exons 9, 11, 13, and 17 (n=10), two
      of them had PDGFRA mutations. KIT amplification was studied by real-time PCR of
      KIT and beta-ACTIN genes, and by fluorescence in situ hybridization (FISH) using
      KIT and chromosome 4 centromere specific probes. KIT transcripts and protein
      expression were quantified by reverse transcription real-time PCR and Western
      blot respectively. Genomic analysis revealed a single mutated GIST with KIT
      amplification. KIT protein and RNA levels were highly variable in GISTs but
      closely correlated (r=0.82, P<1.10(-5)), and were higher in GISTs with KIT
      mutations (P=0.07 and P=0.03 respectively). In conclusion, contrasting with the
      regulation of other tyrosine kinase receptors, KIT overexpression in GISTs is
      rarely related to a gene amplification, which suggests a deregulation of KIT gene
      transcription.

PMID- 15869871
TI  - Ascorbic acid decreases morphine self-administration and withdrawal symptoms in
      rats.
AB  - Recent studies have indicated that the glutamatergic system is involved in the
      motivational aspects during the initiation of drug self-administration. Ascorbic
      acid (AA), an antioxidant vitamin, is released from glutamatergic neurons, and it
      modulates the synaptic action of dopamine and glutamate. In this study the AA
      effects on the self-administration of morphine and on the morphine withdrawal
      syndrome have been investigated. Wistar rats were allowed to self-administer
      morphine (1 mg/infusion) during 10 consecutive days for 2 h/session. The number
      of lever pressings was recorded. An intrapritoneal AA injection (500 mg/kg,
      i.p.), 30 min before morphine self-administration produced a significant decrease
      in the initiation of morphine self administration during all sessions. After the
      last test session morphine withdrawal symptom signs (MWS) were recorded after
      naloxone precipitation. Most of MWS (but not all) were decreased by AA
      application. In conclusion, AA may change the motivational processes underlying
      the morphine self-administration.

PMID- 15869872
TI  - Mechanisms of hyperbaric oxygen and neuroprotection in stroke.
AB  - Cerebral vascular diseases, such as neonatal encephalopathy and focal or global
      cerebral ischemia, all result in reduction of blood flow to the affected regions,
      and cause hypoxia-ischemia, disorder of energy metabolism, activation of
      pathogenic cascades, and eventual cell death. Due to a narrow therapeutic window
      for neuroprotection, few effective therapies are available, and prognosis for
      patients with these neurological injuries remains poor. Hyperbaric oxygen (HBO)
      has been used as a primary or adjunctive therapy over the last 50 years with
      controversial results, both in experimental and clinical studies. In addition,
      the mechanisms of HBO on neuroprotection remain elusive. Early applications of
      HBO within a therapeutic window of 3-6h or delayed but repeated administration of
      HBO can either salvage injured neuronal tissues or promote neurobehavioral
      functional recovery. This review explores the discrepancies between experimental
      and clinical observations of HBO, focusing on its therapeutic window in brain
      injuries, and discusses the potential mechanisms of HBO neuroprotection.

PMID- 15869873
TI  - Immunophenotypic cell lineage and in vitro cellular drug resistance in childhood
      relapsed acute lymphoblastic leukaemia.
AB  - At relapse, T-cell acute lymphoblastic leukaemia (ALL) has a worse patient
      outcome than B-cell precursor (BCP-) ALL. To investigate this further, we
      compared in vitro cellular drug resistance profiles of T-cell and BCP-ALL samples
      obtained at relapse. We investigated 237 paediatric relapsed ALL cases, including
      151 samples taken at first relapse, of which 30 were T-cell ALL. In vitro drug
      resistance was measured using the 4-day methyl-thiazol-tetrazolium (MTT) assay
      and cellular immunophenotype was determined at central reference laboratories.
      Similar results were found for first relapsed ALL samples and for the total
      group: T-cell ALL samples were more resistant to 4-HOO-ifosfamide (1.4-fold, P =
      0.019) and cisplatin (3.7-fold, P = 0.005). The samples were more sensitive to
      thiopurines such as mercaptopurine (2.1-fold, P = 0.007) and thioguanine (1.7
      fold, P = 0.003). Resistance/sensitivity to 16 other drugs did not differ
      significantly. These results do not explain the relatively poor prognosis of T
      cell ALL at relapse, but do suggest that the more intensive use of thiopurines in
      relapsed T-cell ALL may be beneficial.

PMID- 15869874
TI  - Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is a very common neoplastic disease in countries where
      hepatitis viruses B and/or C are prevalent. Small hepatocellular carcinoma
      lesions detected by ultrasonography at an early stage are often hyperechoic
      because they are composed of well-differentiated cancer cells that are rich in
      triglyceride droplets. The triglyceride content of hepatocytes depends in part on
      the rate of lipogenesis. Key lipogenic enzymes, such as fatty acid synthase, are
      co-ordinately regulated at the transcriptional level. We therefore examined the
      mRNA expression of lipogenic enzymes in human hepatocellular carcinoma samples
      from 10 patients who had undergone surgical resection. All of the samples
      exhibited marked elevation of expression of mRNA for lipogenic enzymes, such as
      fatty acid synthase, acetyl-CoA carboxylase and ATP citrate lyase, compared with
      surrounding non-cancerous liver tissue. In contrast, the changes in mRNA
      expression of SREBP-1, a transcription factor that regulates a battery of
      lipogenic enzymes, did not show a consistent trend. In some cases where SREBP-1
      was elevated, the main contributing isoform was SREBP-1c rather than SREBP-1a.
      Thus, lipogenic enzymes are markedly induced in hepatocellular carcinomas, and in
      some cases SREBP-1c is involved in this activation.

PMID- 15869875
TI  - Survival of adults treated for medulloblastoma using paediatric protocols.
AB  - We retrospectively studied 26 consecutive adults treated for medulloblastoma
      using paediatric protocols. Between 1987 and 2003, patients 18 years old were
      given adjuvant chemotherapy consisting of one of two 'paediatric' regimens
      (depending on the time of presentation) and craniospinal local-boost
      radiotherapy: regimen A (n = 12), vincristine (VCR), intrathecal and/or
      intravenous methotrexate and conventional radiotherapy; or regimen B (n = 11)
      sequencing intensive doses of multiple agents followed by hyperfractionated
      accelerated radiotherapy (HART). A VCR-lomustine-based maintenance followed both
      regimens. Three additional patients received a tailored treatment due to their
      impaired neurological status after surgery. The median age at diagnosis was 26
      years (range 18-41 years). With a median follow-up of 46 months, 5-year disease
      free and overall survival rates were 65+/-11% and 73+/-10%, respectively, for the
      series as a whole. All patients who received regimen B (5 of whom had metastatic
      Chang M2-M3 disease) are alive with no evidence of disease at 39 months. Although
      the number of patients is limited, our data suggest that the sandwich sequential,
      moderately intensive chemotherapy in combination with HART is an effective
      treatment for medulloblastoma in adults, and this approach seems to overcome
      previously-recognised risk factors.

PMID- 15869876
TI  - Formation of DNA interstrand cross-links as a marker of Mitomycin C bioreductive
      activation and chemosensitivity.
AB  - Tumour response to Mitomycin C (MMC) is heterogenous and past attempts to predict
      clinical response based on enzyme activities have proven unsatisfactory. Using in
      vitro techniques, the aim of this study was to determine if the induction of DNA
      interstrand cross-links correlated with cellular response and to assess if DNA
      repair and induction of apoptosis influenced MMC chemosensitivity. Poor
      correlations were found between sensitivity and both DNA repair and induction of
      apoptosis suggesting that these processes do not play a major role in determining
      cellular response to MMC. In contrast, there was good correlation between the
      induction of DNA interstrand cross-links as determined by the alkaline comet
      assay and cellular response, suggesting that the biochemical events leading to
      DNA damage are the key factors that determine cellular response in vitro. Further
      studies are required to assess whether this approach as a mean of prediction has
      practical applications in vivo.

PMID- 15869877
TI  - Synthesis and in vitro pharmacological evaluation of salvinorin A analogues
      modified at C(2).
AB  - Salvinorin A is the only known non-nitrogenous and specific kappa-opioid agonist.
      A series of salvinorin A derivatives were prepared and tested for in vitro
      activity at the kappa-opioid receptor. Unsubstituted carbamate 9 was a potent
      kappa-agonist (EC(50) = 6.2 nM) and should be more stable than salvinorin A
      toward metabolic transformations. Compound 10, containing an N-methyl carbamate
      at C(2), showed partial agonist activity with 81% efficacy when compared with the
      full agonist U50,488H. No antagonist ligands were observed.

PMID- 15869878
TI  - Biaryl isoxazolinone antibacterial agents.
AB  - In an era of increasing resistance to classical antibacterial agents, the
      synthetic oxazolidinone series of antibiotics has attracted much interest.
      Zyvoxtrade mark was the first oxazolidinone to be approved for clinical use
      against infections caused by multi-drug resistant Gram-positive bacteria. In the
      course of studies directed toward the discovery of novel antibacterial agents, a
      new series of synthetic phenyl-isoxazolinone agents that displayed potent
      activity against Gram-positive bacterial strains was recently discovered at
      Bristol-Myers Squibb. Extensive investigation of various substitutions on the
      phenyl ring was then undertaken. We report here, the synthesis and antibacterial
      activity of a series of biaryl isoxazolinone compounds.

PMID- 15869879
TI  - Solution conformations of amphidinolide H.
AB  - Solution conformations of amphidinolide H (1), a 26-membered macrolide exhibiting
      potent cytotoxic and antitumor activity, in CDCl3 and DMSO-d6 were investigated
      on the basis of NMR data, distance geometry calculation, and restrained energy
      minimization. Three-dimensional conformations in CDCl3 were suggested to be close
      to the X-ray structure of 1, while those in DMSO-d6 were indicated to be
      different from both those in CDCl3 and the X-ray structure.

PMID- 15869881
TI  - Combinatorial approach to identification of tyrphostin inhibitors of cytokine
      signaling.
AB  - Aberrant or deregulated activity of certain cellular kinases has been shown to
      cause certain malignancies and other disorders. The tyrphostin molecule AG490
      inhibits the action of the janus kinases JAK2 and JAK3. JAK2 is an indispensable
      molecule for transducing the signals conveyed by a large number of cytokines
      including IL-3 while JAK3 is essential for signaling by a smaller number of
      cytokines including IL-7. A synthetic combinatorial chemical library containing
      599 compounds was created and screened for the ability to inhibit proliferation
      of IL3- and IL7-dependent cell lines to focus on molecules that interrupt those
      signaling pathways. This screen identified a meta-trifluoromethyl derivative of
      AG490, 5H4, that is approximately twice as potent as AG490 in cell-based assays.
      5H4 blocked the factor-dependent proliferation of both of these cell lines,
      actively promoted cell death, and diminished the JAK kinase activity.
      Administration of 5H4 to lymphoma-prone IL-7 transgenic mice reduced their
      spontaneous lymphadenopathy. The improved characteristics of this novel compound
      bring this class of molecules closer to therapeutic utility.

PMID- 15869880
TI  - Design, synthesis and evaluation of carbazole derivatives as PPAR alpha/gamma
      dual agonists and antioxidants.
AB  - A series of hydroxycarbazole derivatives were synthesized and evaluated for PPAR
      alpha/gamma dual agonist as well as antioxidant activities. While most compounds
      showed good antioxidant activity, some compounds were identified as potential
      PPAR alpha/gamma dual agonists as well. Compounds 10a and 16 were found to be
      active in animal studies.

PMID- 15869883
TI  - Interleukin-12 p40 promoter activity is regulated by the reversible acetylation
      mediated by HDAC1 and p300.
AB  - Interleukin-12 (IL-12) is a heterodimeric cytokine produced by macrophages in
      response to intracellular pathogens. The importance of IL-12 in generation of Th1
      response against human pathogens has been characterized. The coactivator p300 is
      an important histone acetyltransferase (HAT) and has been implicated in the
      regulation of many genes. Histone deacetylases (HDACs) regulate gene
      transcription through deacetylation of histones. Whether the reversible histone
      acetylation/deacetylation modification participates in the regulation of IL-12
      p40 transcription expression has not been investigated before. In this study, we
      analyzed the roles of HDAC1 and p300 in the regulation of human IL-12 p40. Co
      transfection studies showed that HDAC1 had a repressing effect on the activity of
      IL-12 p40 promoter. Contrarily, p300 was able to reinforce the C/EBPbeta-mediated
      activation of IL-12 p40 and it counteracted the HDAC1-mediated repression of the
      IL-12 promoter. Chromatin immunoprecipitation tests (ChIP) revealed that p300 had
      a stimulating effect on the acetylation of the histone H3 at IL-12 p40 promoter.
      In addition, we showed that p300 had a physical interaction with C/EBPbeta and
      can enhance acetylation of C/EBPbeta. Data presented in this paper indicate that
      the reversible histone acetylation/deacetylation modification plays an important
      role in the transcriptional regulation of IL-12.

PMID- 15869882
TI  - Gene expression alterations of human peripheral blood monocytes induced by medium
      term treatment with the TH2-cytokines interleukin-4 and -13.
AB  - The TH2-cytokines interleukins-4 and -13 severely alter gene expression of
      monocytic cells. We quantified the impact of interleukins-4 and -13 on the gene
      expression pattern of human peripheral blood monocytes applying a strategy that
      involved microarray hybridization, RT-PCR, immunohistochemistry and activity
      assays. After 3 days of continuous cytokine exposure the six most strongly
      upregulated gene products (15-lipoxygenase-1, fibronectin, monoamine oxidase-A,
      CD1c, CD23A, coagulation factor XIII) included four proteins with potential anti
      inflammatory properties: (i) 15-lipoxygenase-1 (290-fold upregulation), (ii)
      fibronectin (180-fold upregulation), (iii) monoamine oxidase-A (56-fold
      upregulation) and (iv) coagulation factor XIII (35-fold upregulation). In
      addition, a number of other gene products, the expression of which is consistent
      with inflammatory resolution (annexin 1, collagen 1alpha2, laminin alpha5, TIMP3,
      heme oxygenase-1, CCL22, heat shock protein A8), were upregulated to a lower
      extent. In contrast, expression of classical pro-inflammatory gene products, such
      as tumor necrosis factor alpha, monocyte chemotactic protein-1, interleukins-1, 
      6, -8, -18, cyclooxygenase-2, as well as enzymes and receptors of the leukotriene
      cascade (5-lipoxygenase, 5-lipoxygenase activating protein, leukotriene B(4)
      receptor, cysteinyl leukotriene receptor 2) were significantly downregulated.
      These data suggest that medium-term treatment of human peripheral blood monocytes
      with interleukins-4/13 alters the gene expression pattern so that the cells might
      adopt a resolving phenotype.

PMID- 15869884
TI  - Expression of a bioactive recombinant human interleukin-11 in chicken HD11 cell
      line.
AB  - To direct the synthesis and secretion of recombinant human interleukin-11 (rhIL
      11) in chicken HD11 cells, a plasmid targeting the c-lysozyme gene has been
      constructed which contains the mature cytokine cDNA in frame with the lysozyme
      leader sequence. The upregulation of rhIL-11 mediated by LPS proves the knock-in
      of hIL-11 cDNA in the lysozyme gene. The bioactivity of the expressed protein is
      demonstrated and quantified with the hIL-11 dependent 7TD1 and B9 cell lines. The
      electrophoretic mobility, receptor binding properties and growth promoting effect
      of the chicken-derived cytokine are identical to those of a rhIL-11 expressed in
      Escherichia coli. These results describe the secretion of a biologically active
      rhIL-11 expressed by an avian cellular machinery.

PMID- 15869885
TI  - Molecular phylogeny of North American long-eared bats (Vespertilionidae:
      Corynorhinus); inter- and intraspecific relationships inferred from mitochondrial
      and nuclear DNA sequences.
AB  - The taxonomy of the North American big-eared bats, genus Corynorhinus, was
      revised by Handley [Handley, C.O., 1959. A revision of the American bats of the
      genera Euderma and Plecotus. Proc. U.S. Nat. Mus. 110, 95-246] using a
      morphological systematics approach. Handley employed 17 morphological characters
      and identified only four characters that reliably differentiated the three
      species he recognized, C. townsendii, C. rafinesquii, and C. mexicanus. All three
      species have been shown to lead relatively sedentary lives and have a wing
      morphology that limits long-distance dispersal. Further, populations of two
      species, C. townsendii and C. rafinesquii, are considered to be declining.
      Handley [Handley, C.O., 1959. A revision of the American bats of the genera
      Euderma and Plecotus. Proc. U.S. Nat. Mus. 110, 95-246] recognized five
      subspecies of C. townsendii (C. t. australis, C. t. ingens, C. t. pallescens, C.
      t. townsendii, and C. t. virginianus) and two of C. rafinesquii (C. r.
      rafinesquii and C. r. macrotis). Two C. townsendii subspecies, C. t. ingens and
      C. t. virginianus, are listed as endangered under the Endangered Species Act.
      These facts and the lack of a thorough molecular systematic examination of this
      genus were the impetus for this study. Using mitochondrial and nuclear intron DNA
      sequences, a molecular phylogeny was inferred. The combined DNA phylogeny
      supports Handley's [Handley, C.O., 1959. A revision of the American bats of the
      genera Euderma and Plecotus. Proc. U. S. Nat. Mus. 110, 95-246] designation of
      three species. Further the endangered subspecies, C. t. ingens and C. t.
      virginianus are corroborated, as were the monophyly of the other subspecies.
      However, the geographical ranges of two of these subspecies, C. t. pallescens and
      C. t. townsendii, are revised based on biogeographic distributions as understood
      from our results. Estimates of timing of divergences indicate that the three
      species, C. townsendii, C. rafinesquii, and C. mexicanus may have diverged before
      Pleistocene climatic oscillations began, and therefore their cladogenesis was not
      the result of those processes. However, subspecific divergences within C.
      townsendii appear to have occurred during and been driven largely by the climatic
      processes of the Pleistocene Epoch. We propose new hypotheses of dispersal
      scenarios that may have led to the current biogeography of these lineages.

PMID- 15869886
TI  - Phylogeographic analysis of the Bufo gargarizans species complex: a revisit.
AB  - Using mtDNA sequencing and allozyme electrophoresis data, we tested the
      "vicariance followed by dispersal" hypothesis of the Bufo gargarizans species
      group and re-evaluated the species status in the general lineages species
      concept. A phylogenetic analysis suggested that dispersal, instead of vicariance,
      dominated the history of the species group. There was a general trend of west to
      east dispersal, while some lineages from the east subsequently returned to the
      west. The secondary admixture of those previously allopatric lineages produced
      substantial levels of sympatric genetic diversity, often as high as 7.0% pairwise
      difference within populations. The phylogenetic hypothesis does not support the
      current two species designation. Neither B. andrewsi nor B. gargarizans
      represents an independent evolutionary lineage, and monophyletic groups did not
      correspond to geographically discrete groups. Allozyme data also failed to reveal
      any fixed allelic difference among the populations. Therefore, we recommend
      regarding the complex as a single species, Bufo gargarizans, without subspecies
      division.

PMID- 15869887
TI  - A phylogenetic analysis of woodpeckers and their allies using 12S, Cyt b, and COI
      nucleotide sequences (class Aves; order Piciformes).
AB  - Although the woodpeckers have long been recognized as a natural, monophyletic
      taxon, morphological analyses of their intra- and intergeneric relationships have
      produced conflicting results. To clarify this issue, and as part of a larger
      study of piciform relationships, nucleotide sequences for the 12S ribosomal RNA
      (12S; 1123 bp), cytochrome b (Cyt b; 1022 bp), and cytochrome oxidase c subunit 1
      (COI; 1512 bp) mitochondrial genes were obtained from 34 piciform species that
      included 16 of the 23 currently recognized woodpecker genera (subfamily Picinae),
      three piculets (subfamily Picumninae), a wryneck (subfamily Jynginae), a
      honeyguide (family Indicatoridae), and three barbets (infraorder Ramphastides).
      Analyses were conducted on the individual and combined 12S, Cyt b, and COI
      sequences with maximum parsimony, neighbor-joining, maximum likelihood, and
      Bayesian algorithms. Based on the strong, congruent support among the different
      data partitions and models of sequence evolution, a highly resolved consensus of
      the relationships among woodpeckers and their allies could be formed. The
      monophyly of Indicatoridae + Picidae (infraorder Picides), Picidae, Picinae +
      Picumninae, and Picinae was strongly supported in all analyses. However, the
      tribes Colaptini, Picini, Campephilini, and Campetherini were shown to be
      paraphyletic as were the genera of Colaptes and Piculus. A revision of the tribal
      level classification of woodpeckers is proposed and the importance of plumage
      convergence among woodpeckers is discussed.

PMID- 15869888
TI  - Genetic control of an epigenetic cell degeneration syndrome in Podospora
      anserina.
AB  - Filamentous fungi frequently present degenerative processes, whose molecular
      basis is very often unknown. Here, we present three mutant screens that result in
      the identification of 29 genes that directly or indirectly control Crippled
      Growth (CG), an epigenetic cell degeneration of the filamentous ascomycete
      Podospora anserina. Two of these genes were previously shown to encode a MAP
      kinase kinase kinase and an NADPH oxidase involved in a signal transduction
      cascade that participates in stationary phase differentiations, fruiting body
      development and defence against fungal competitors. The numerous genes identified
      can be incorporated in a model in which CG results from the sustained activation
      of the MAP kinase cascade. Our data also emphasize the complex regulatory network
      underlying three interconnected processes in P. anserina: sexual reproduction,
      defence against competitors, and cell degeneration.

PMID- 15869889
TI  - Drifter, a novel, low copy hAT-like transposon in Fusarium oxysporum is activated
      during starvation.
AB  - The facultative pathogenic fungus Fusarium oxysporum is known to harbour many
      different transposable and/or repetitive elements. We have identified Drifter, a
      novel DNA transposon of the hAT family in F. oxysporum. It was found adjoining
      SIX1-H, a truncated homolog of the SIX1 avirulence gene in F. oxysporum f. sp.
      lycopersici. Absence of a target site duplication as well as the 5' part of SIX1
      H suggests that transposition of Drifter into the ancestor of SIX1-H was followed
      by loss of a chromosomal segment through recombination between Drifters. F.
      oxysporum isolates belonging to various formae speciales harbour between 0 and 5
      full-length copies of Drifter and/or one or more copies with an internal
      deletion. Transcription of Drifter is activated during starvation for carbon or
      nitrogen.

PMID- 15869890
TI  - On concomitant gradients in low-field MRI.
AB  - Growing interest in magnetic resonance imaging (MRI) at ultra-low magnetic fields
      (ULF, approximately muT fields) has been motivated by several advantages over its
      counterparts at higher magnetic fields. These include narrow line widths, the
      possibility of novel imaging schemes, reduced imaging artifacts from
      susceptibility variations within a sample, and reduced system cost and
      complexity. In addition, ULF NMR/MRI with superconducting quantum interference
      devices is compatible with simultaneous measurements of biomagnetic signals, a
      capability conventional systems cannot offer. Acquisition of MRI at ULF must,
      however, account for concomitant gradients that would otherwise result in severe
      image distortions. In this paper, we introduce the general theoretical framework
      that describes concomitant gradients, explain why such gradients are more
      problematic at low field, and present possible approaches to correct for these
      unavoidable gradients in the context of a non-slice-selective MRI protocol.

PMID- 15869891
TI  - Determination of orientation distribution function of anisotropic paramagnetic
      species by analysis of ESR spectra angular dependence.
AB  - A method has been developed to determine orientation distribution function (ODF)
      of anisotropic paramagnetic species by analysis of the angular dependence of the
      ESR spectra. The method is based on computational spectra simulation. The ODF is
      represented as an expansion in terms of orthonormal functions. The expansion
      coefficients are determined through minimization of discrepancies between
      simulated spectra and experimental ones. By means of the suggested method we have
      determined the orientation distribution functions for radical probe 2,2,6,6
      tetramethyl-4-ol-piperidinooxyl in 4-n-amyl-4'-cyanobiphenyl aligned by magnetic
      field and 2-septadecyl-2,3,4,5,5-pentamethylimidazolidine in polyethylene
      stretched films. In each case, thermal evolution of the ODF has been
      investigated.

PMID- 15869892
TI  - Computing the B1 field of the toroidal MRI coil.
AB  - We present an analytic solution for the B1 field produced in a gapped toroidal
      cavity resonator designed as a probe for high field MRI. This resonator supports
      standing TEM waves, so its electric and magnetic fields are identical to those
      produced by a stationary planar current source with the same (constant) cross
      section multiplied by a complex exponential propagation factor. An explicit
      expression for the field may therefore be found by solving Laplace's equation for
      the static potential, which is accomplished with a two-dimensional logarithmic
      conformal transformation algorithm. The equipotential curves are also the
      contours of the field strength B, and the B (vector) field at any point is
      directed along the contour passing through that point. With this information, we
      construct the solution by computing the angle made by the equipotential curve
      with the horizontal axis at each point, using this angle to analyze the B field
      into its x and y components, and adding the contributions from the current
      sources to obtain the magnitude and direction of B at each point in the region of
      interest. Some proposed extensions of this algorithm are also discussed.

PMID- 15869893
TI  - A study of the spin-echo spin-locking effect in multi-pulse sequences in 14N
      nuclear quadrupole resonance.
AB  - Experimental evidence of observing a rather unusual spin-locking spin echo (SLSE)
      effect in the fields of two multi-pulse sequences (varphi(0))(x)-(tau-varphi(x)
      2tau-varphi(x)-2tau-varphi(-x)-2tau-varphi(-x)-tau)(n) and (varphi(0))(x)-(tau
      varphi(x)-2tau-varphi(y)-tau)(n) in (14)N nuclear quadrupole resonance is
      presented. It was demonstrated that the SLSE effect is observed only in the even
      pulse intervals of both sequences. All experiments were carried out at room
      temperature on a powder sample of NaNO2. A theoretical description of the effect
      is given.

PMID- 15869894
TI  - Physiological modelling of agitation-sedation dynamics.
AB  - Agitation-sedation cycling in critically ill patients, characterized by
      oscillations between states of agitation and over-sedation, damages patient
      health and increases length of stay and cost. A model that captures the essential
      dynamics of the agitation-sedation system and is physiologically representative
      is developed, and validated using data from 37 critical care patients. It is more
      physiologically representative than a previously published agitation-sedation
      model, and captures more realistic and complex dynamics. The median time in the
      90% probability band is 90%, and the total drug dose, relative to recorded drug
      dose data, is a near ideal 101%. These statistical model validation metrics are 5
      13% better than a previously validated model. Hence, this research provides a
      platform to develop and test semi-automated sedation management controllers that
      offer the significant clinical potential of improved agitation management and
      reduced length of stay in critical care.

PMID- 15869895
TI  - Modelling the passive and nerve activated response of the rectus femoris muscle
      to a flexion loading: a finite element framework.
AB  - A muscle modelling framework is presented which relates the mechanical response
      of the rectus femoris muscle (at the organ level) to tissue level properties,
      with the capability of linking to the cellular level as part of the IUPS Physiome
      Project. This paper will outline our current approach to muscle modelling
      incorporating micro-structural passive and active properties including fibre
      orientations and nerve innervation. The technique is based on finite deformation
      (using FE analysis) coupled to electrical nerve initiated muscle activation, and
      we present the influence of active tension through an eccentric contraction at
      specific flexion angles. Finally we discuss the future goals of incorporating
      cell mechanics and validating at the organ level to provide a complete diagnostic
      tool with the ability to relate mechanisms of failure across spatial scales.

PMID- 15869896
TI  - On the use of PRD and CR parameters for ECG compression.
AB  - The quality measurement of the reconstructed signal in an electrocardiogram (ECG)
      compression scheme must be obtained by objective means being the percentage root
      mean-square difference (PRD) the most widely used. However, this parameter is
      dependent on the dc level so that confusion can be stated in the evaluation of
      ECG compressors. In this communication, it will be shown that if the performance
      of an ECG coder is evaluated only in terms of quality, considering exclusively
      the PRD parameter, incorrect conclusions can be inferred. The objective of this
      work is to propose the joint use of several parameters, as simulations will show,
      effectiveness and performance of the ECG coder are evaluated with more precision,
      and the way of inferring conclusions from the obtained results is more reliable.

PMID- 15869897
TI  - Retinoic acid determines life span of leukemic cells by inducing antagonistic
      apoptosis-regulatory programs.
AB  - As a single signal, retinoids induce terminal differentiation. This implies that
      they activate differentiation and apoptosis in a temporally defined order to
      allow expression of the differentiated phenotype well before death. We report
      that two apparently contradictory retinoid-induced programs have the capacity to
      define cellular life span. Anti-apoptotic factors are activated concomitantly
      with differentiation, while retinoids induce at the same time also pro-apoptotic
      signaling. We have assessed the roles of two key factors, Bcl2A1 and TRAIL, in
      the temporal programming of cell death and differentiation. We demonstrate that
      PLB985 are type II cells in which TRAIL induces apoptosis through the extrinsic
      and--via Bid activation--also the intrinsic death pathways. Bcl2A1, ectopically
      over-expressed, or endogenously induced by retinoic acid receptor agonists,
      protected cells from apoptosis triggered by TRAIL, whose induction required the
      activation of both the retinoic acid and retinoid X receptors. Bcl2A1 prevented
      loss of mitochondrial membrane potential and caspase-9, but not caspase-8,
      activation. The expression of anti-sense Bcl2A1 sensitized PLB985 cells to TRAIL.
      Co-culture experiments revealed protection from fraternicide if sister cells were
      pre-exposed to retinoic acid. Collectively, our data support a model in which
      retinoids orchestrate a life span-regulatory program comprising Bcl2A1 induction
      to temporally protect against concomitantly induced TRAIL death signaling.
      Termination of this life span in presence of Bcl2A1 is most likely a consequence
      of the Bid-independent TRAIL action. Thus, depending on the retinoic acid and
      retinoid X receptor activation potential of a ligand and the relative efficacies
      of the intrinsic and extrinsic death pathways in a given cell, a single retinoid
      triggers the life span of a differentiated phenotype.

PMID- 15869898
TI  - The role of bone morphogenetic proteins in endochondral bone formation.
AB  - Bone morphogenetic proteins (BMPs) were originally identified as proteins capable
      of inducing endochondral bone formation when implanted at extraskeletal sites.
      BMPs have diverse biological activities during early embryogenesis and various
      aspects of organogenesis. BMPs bind to BMP receptors on the cell surface, and
      these signals are transduced intracellularly by Smad proteins. BMP signal
      pathways can be inhibited by both extra- and intracellular mechanisms. As for
      skeletal development, genetic studies suggest that BMPs are skeletal mesoderm
      inducers. Recent studies of tissue-specific activation and inactivation of BMP
      signals have revealed that BMP signals control proliferation and differentiation
      of chondrocytes, differentiation of osteoblasts and bone quality. These findings
      may contribute not only to understanding of bone biology and pathology, but also
      to improvement of the clinical efficacy of BMPs.

PMID- 15869899
TI  - MicroRNAs: Small regulators with a big impact.
AB  - MicroRNAs (miRNA) are non-coding small (approximately 22nt) RNAs that regulate
      diverse physiological and developmental processes. In animals, they regulate
      target genes by binding imperfectly to 3'UTR sequences in mRNAs and attenuate
      translation. There are hundreds of miRNA genes in animals, and current studies
      show they constitute a minimum of 1% of known genes. We are just beginning to
      understand the diverse roles they play in cellular processes, which include
      signaling pathways, developmental pathways, and possibly various types of
      cancers.

PMID- 15869900
TI  - SOST/sclerostin, an osteocyte-derived negative regulator of bone formation.
AB  - Sclerosteosis and Van Buchem disease are two closely related bone disorders
      characterized by progressive bone thickening due to increased bone formation.
      Sclerosteosis is associated with mutations in the SOST gene and Van Buchem
      disease with a 52 kb deletion downstream of the SOST gene that probably affects
      transcription of the gene. Expression of the gene product sclerostin in bone is
      restricted to osteocytes and it is a negative regulator of bone formation. It
      inhibits BMP-stimulated bone formation, but cannot antagonize all BMP responses.
      The exclusive bone phenotype of good quality of patients with sclerosteosis and
      Van Buchem disease and the specific localization of sclerostin make it an
      attractive target for the development of bone forming therapeutics.

PMID- 15869901
TI  - Resistance to tyrosine kinase inhibitors: calling on extra forces.
AB  - Over the past 5 years, small molecule tyrosine kinase inhibitors have been
      successfully introduced as new cancer therapeutics. The pioneering work with the
      ABL inhibitor imatinib (Glivec, Gleevec) was rapidly extended to other types of
      leukemias as well as solid tumors, which stimulated the development of a variety
      of new tyrosine kinase inhibitors. Unfortunately, oncogenic tyrosine kinases seem
      to have little problem to develop resistance to these inhibitors, and there is
      good evidence that this is not limited to imatinib, but also occurs with other
      inhibitors, such as FLT3 and EGFR inhibitors. Based on studies with imatinib,
      mutation and amplification of the target kinase seem to be the most important
      mechanisms for the development of resistance, but these mechanisms alone cannot
      explain all cases of resistance. A better understanding of the resistance
      mechanisms will be required to design improved treatment strategies in the
      future. In this review, we summarize the current insights in the different
      mechanisms of resistance to small molecule tyrosine kinase inhibitors, and
      discuss future improvements that might limit or even overcome resistance.

PMID- 15869902
TI  - Non-thermal DNA breakage by mobile-phone radiation (1800 MHz) in human
      fibroblasts and in transformed GFSH-R17 rat granulosa cells in vitro.
AB  - Cultured human diploid fibroblasts and cultured rat granulosa cells were exposed
      to intermittent and continuous radiofrequency electromagnetic fields (RF-EMF)
      used in mobile phones, with different specific absorption rates (SAR) and
      different mobile-phone modulations. DNA strand breaks were determined by means of
      the alkaline and neutral comet assay. RF-EMF exposure (1800 MHz; SAR 1.2 or 2
      W/kg; different modulations; during 4, 16 and 24h; intermittent 5 min on/10 min
      off or continuous wave) induced DNA single- and double-strand breaks. Effects
      occurred after 16 h exposure in both cell types and after different mobile-phone
      modulations. The intermittent exposure showed a stronger effect in the comet
      assay than continuous exposure. Therefore we conclude that the induced DNA damage
      cannot be based on thermal effects.

PMID- 15869903
TI  - Does genotype of hepatitis A virus relate to clinical characteristics of
      hepatitis A?

PMID- 15869904
TI  - Survival benefits of intra-arterial infusion chemotherapy in patients with
      advanced hepatocellular carcinoma with portal vein tumor thrombosis.
AB  - PURPOSE: : Advanced hepatocellular carcinoma (HCC) with portal vein thrombosis
      has a poor prognosis. This study was undertaken to evaluate the therapeutic
      effects of intra-arterial infusion chemotherapy in advanced HCC, and tried to
      identify prognostic factors that could affect survival. METHODS AND MATERIALS: :
      Between January 1995 and January 2001, a total of 102 patients with advanced HCC
      with portal vein thrombosis were enrolled and divided into three groups: group 1
      (n=24) was managed with only supportive care, group 2 (n=25) received systemic
      combination chemotherapy and group 3 (n=52) received intra-arterial infusion
      chemotherapy with 5-fluorouracil+cisplatin via implanted chemoport. RESULTS: :
      One-year survival rates were 0, 4, 21% and median survivals were 2, 4, 6 months
      in groups 1, 2, 3, respectively (p=0.003). When we divide group 3 patients into
      long-term (more than 8 months) or short-term survivors, long-term survivor had
      significantly low level of serum AST (p=0.032) and alkaline phosphatase
      (p=0.033). Especially, all female patients (n=9) survived more than 8 months
      (p=0.000). Other favorable prognostic factors for survival were cirrhosis of
      Child-Pugh class A (p=0.003), only one major branch involvement of the portal
      vein by tumor (p=0.005), presence of enhancement of tumor portion in arterial
      phase of CT scan (p=0.044), presence of enhancement of non-tumor portion in
      portal phase of CT scan (p=0.029). CONCLUSIONS: : Intra-arterial infusion
      chemotherapy achieved favorable results in advanced HCC with portal vein
      thrombosis and showed better survival in selected patients.

PMID- 15869905
TI  - Haematoma after coronary angiography and percutaneous coronary intervention via
      the femoral artery frequency and risk factors.
AB  - BACKGROUND: The most common complication after coronary angiography (CA) and
      percutaneous coronary intervention (PCI) is the development of haematoma. Several
      changes in procedures regarding CA and PCI have been made in our department in
      recent years. The aim of this audit is to establish how many patients develop
      haematoma after CA/PCI via the femoral artery and subsequently to find predictors
      that increase the risk of developing haematoma. METHODS: We initially included
      474 consecutive patients-322 patients undergoing CA and 141 patients undergoing
      PCI. Eleven patients were later excluded due to the absence of complete data.
      Thirty-three variables were registered in order to find predictors, which might
      increase the haematoma frequency. A univariate as well as a multivariate logistic
      regression analysis was performed. RESULTS: Of the 463 patients, 6 patients
      developed a haematoma >10 cm (1.3%) and 41 patients developed a haematoma >5 cm
      (8.9%). The following factors were found to be associated with the generation of
      haematoma: Women, systolic blood pressure >160 mm Hg, artery puncture >1, sheath
      time >16 min, ACT > or = 175 s, Glycoprotein (GP) IIB/IIIa inhibitors, Low
      Molecular Weight Heparin before procedure, personnel change during compression,
      and anti-coagulant-treatment before procedure. CONCLUSIONS: The frequency of
      haematoma was 1.3% (>10 cm) and 8.9% (>5 cm), which corresponds with reports from
      similar studies and departments. The factors found to increase the risk of
      haematoma development can provide background for procedural changes and increase
      the focus on patients at increased risk in order to minimize the development of
      haematomas.

PMID- 15869906
TI  - Pulsed tissue Doppler and strain imaging discloses early signs of infiltrative
      cardiac disease: a study on patients with familial amyloidotic polyneuropathy.
AB  - BACKGROUND: Familial amyloidotic polyneuropathy (FAP) is a hereditary systemic
      amyloidosis with cardiac involvement. As early identification of the cardiac
      involvement is of major clinical interest we performed this study to test the
      hypothesis that tissue Doppler imaging (TDI) and strain imaging (SI) might
      disclose cardiac involvement in patients with early stages of FAP. METHODS:
      Twenty-two patients with FAP and 36 healthy controls were studied. Standard M
      mode and Doppler echocardiography were performed. TDI and SI were used to assess
      the regional longitudinal left ventricular (LV) lateral and septal and right
      ventricular (RV) wall functions. All time intervals were corrected for heart rate
      by dividing with R-R interval and presented as percentage. RESULTS: We found that
      patients in comparison with controls had increased LV and RV wall thickness and
      by using TDI a prolonged isovolumic relaxation time (IVRt) at the septal segment
      (15.0+/-7.0 vs 10.7+/-4.1%, p<0.05) and prolonged isovolumic contraction time
      (IVCt) at LV lateral (12.8+/-4.3 vs 10.1+/-3.3%, p<0.05), septal (12.5+/-3.5 vs
      8.9+/-1.9%, p<0.001) and RV free wall segments (12.0+/-3.6 vs 8.3+/-2.1%,
      p<0.001). Strain was reduced at LV lateral basal segment (-4.6+/-14.0 vs 
      20.2+9.1, p<0.001), RV free wall mid segment (-16.2+/-12.8 vs -29.4+/-15.2) as
      well as both septal segments (-4.1+/-11.7 vs -16.2+/-9.0%, p<0.001, -8.8+/-11.5
      vs -19.4+/-8.4%, p<0.001 for septal basal and mid-segment). Even in the absence
      of septal hypertrophy the septal strain was reduced and the regional IVCt was
      prolonged. CONCLUSIONS: This is the first clinical study using TDI and strain in
      patients with FAP showing functional abnormalities before any morphological
      echocardiographic abnormalities were present. Both the left and right heart
      functions are involved and the disease should therefore be regarded as
      biventricular.

PMID- 15869907
TI  - Impact of epilepsy in adolescence: a UK controlled study.
AB  - PURPOSE: The goals of the work described here were to investigate the
      psychological and social impact of epilepsy on adolescents and to identify to
      what degree clinical and demographic variables and knowledge of epilepsy could
      influence psychosocial functioning. METHODS: Seventy adolescents with epilepsy
      were compared with healthy controls (matched for age, sex, and reading ability)
      on measures of self-esteem, social adjustment, depression, and obsession. Within
      the epilepsy group, the impact of seizure frequency, seizure severity, and
      knowledge of epilepsy on the above measures was also determined. RESULTS:
      Adolescents with epilepsy showed significantly higher levels of depression,
      anhedonia, and social anxiety and significantly higher numbers of obsessive
      symptoms than the adolescents without epilepsy. Among the adolescents with
      epilepsy, high seizure frequency was significantly associated with low self
      esteem, and tonic-clonic seizures were specifically associated with higher levels
      of depression. Finally, low levels of epilepsy knowledge were significantly
      associated with higher levels of depression, lower levels of self-esteem, and
      higher levels of social anxiety. CONCLUSIONS: Epilepsy has a significant
      psychosocial impact on adolescents at this difficult time of life. Social support
      and access to appropriate information about epilepsy could be of help.

PMID- 15869908
TI  - Response to The UCSD Statin Study: a randomized controlled trial assessing the
      impact of statins on selected noncardiac outcomes".

PMID- 15869909
TI  - The effect of ventilation on spectral analysis of heart rate variability during
      exercise.

PMID- 15869910
TI  - Simultaneous determination of histamine and polyamines by capillary zone
      electrophoresis with 4-fluor-7-nitro-2,1,3-benzoxadiazole derivatization and
      fluorescence detection.
AB  - Capillary zone electrophoresis (CZE) with fluorescence detection was applied to
      the simultaneous determination of histamine and polyamines including spermine,
      spermidine, diaminopropane, putrescine, cadaverine, diaminohexane with 4-fluor-7
      nitro-2,1,3-benzoxadiazole (NBD-F) as the fluorescent derivatization reagent. The
      seven NBD-F labeled amines was separated within 200 s using 85 mM phosphate
      running buffer at pH 3.0. The concentration limits of these amines ranged from
      5.1 x 10(-8) M for spermine to 2.1 x 10(-8) M for histamine. The relative
      standard deviations for migration time and peak height were less than 1.5% and
      6.0%, respectively. The method was successfully applied to the analysis of
      biogenic amines in the lysate of tobacco mesophyll protoplasts, and spermidine
      and putrescine were detected in the lysate with satisfying recovery.

PMID- 15869911
TI  - Boom, bust, and the human body: further evidence on the relationship between
      height and business cycles.
AB  - Historical time series for average human height exhibit short- and medium-term
      cycles that can be associated with business cycles in the 19th and 20th century.
      Using spectral analysis, we calculate the proportion of cyclical fluctuations in
      height series attributable to economic cycles. We also analyze the extent to
      which these cyclical phenomena change over time. In the U.S., the association
      between height cycles and business cycles was weaker among richer segments of the
      society, and weaker among men than among women. Additionally, the relationship
      diminished over time, probably with the rich preceding the population at large.

PMID- 15869912
TI  - Psychological status and depression in patients with liver cirrhosis.
AB  - BACKGROUND: Previous studies reported an impairment of both the physical and
      mental dimensions of quality of life in patients with cirrhosis. Very few data
      are available on the psychological impact of the disease and its relation to
      liver function. AIM: To measure the psychological status of patients with
      cirrhosis in relation to the severity of the liver impairment. PATIENTS AND
      METHODS: One hundred and fifty-six patients with cirrhosis were studied. Two
      questionnaires (the Beck Depression Inventory and the Psychological General Well
      Being Index) were self-administered in random order. Clinical and laboratory data
      were collected using standardised forms. RESULTS: The global score of
      Psychological General Well-Being Index was severely reduced compared to Italian
      population norm. Among individual domains, the more severely affected was General
      Health, the less compromised was Positive Well-Being. A negative relation was
      found between Child-Pugh score (a comprehensive measure of disease severity) and
      global Psychological General Well-Being Index and several individual subscales.
      The Beck Depression Inventory scores were indicative of a depressed mood in over
      50% of patients, in relation to the presence of clinical symptoms. CONCLUSIONS:
      Patients with cirrhosis have signs of psychological distress and depression, as
      assessed by Beck Depression Inventory and Psychological General Well-Being Index,
      in relation to the severity of liver disease. Accordingly, a non-negligible
      number of patients warrant treatment.

PMID- 15869913
TI  - Expression of matrix metalloproteinases-2 and -9 in intestinal tissue of patients
      with inflammatory bowel diseases.
AB  - BACKGROUND/AIMS: Matrix metalloproteinases are major contributors in the
      breakdown and reconstitution of basement membranes and extracellular matrix in
      pathophysiological processes. We assessed the expression of matrix
      metalloproteinases-2 and -9 in intestinal tissue of patients with inflammatory
      bowel disease. PATIENTS/METHODS: Resected tissue specimens from patients with
      Crohn's disease or ulcerative colitis and control tissue from patients with a
      colorectal carcinoma were used for enzyme-linked immunosorbent assay, zymography,
      activity assay, reverse transcription polymerase chain reaction and
      immunohistochemistry to evaluate the expression of these matrix
      metalloproteinases. RESULTS: Matrix metalloproteinase-2 and more strongly matrix
      metalloproteinase-9 protein and mRNA were markedly increased in inflammatory
      bowel disease tissues, with the highest levels in severely inflamed tissues.
      Immunohistochemistry showed that matrix metalloproteinase-2 was present in the
      extracellular matrix of the submucosa, with a lower but more generalised
      expression in the severely inflamed regions. Matrix metalloproteinase-9 was most
      prominent in polymorphonuclear leukocytes and was increased, also in activity, in
      all inflammatory bowel disease tissues. An increased matrix metalloproteinase-9
      expression in the extracellular matrix was observed in relation to the severity
      of inflammation. CONCLUSIONS: Matrix metalloproteinases-2 and -9 are enhanced in
      the intestinal tissue and seem to be actively involved in the inflammatory and
      remodelling processes in inflammatory bowel disease, without major differences
      between CD and UC.

PMID- 15869914
TI  - Nitric oxide-nitric oxide synthase regulates key maturational events during
      chondrocyte terminal differentiation.
AB  - The goal of this investigation was to explore the mechanism by which NOS and NO
      serve to regulate events linked to chondrocyte terminal differentiation. NOS
      isoform expression and NO adducts in chick growth cartilage were detected by
      immunohistochemistry and Western blot analysis. All NOS isoforms were expressed
      in chick growth plate chondrocytes with the highest levels present in the
      hypertrophic region. The enzymes were active since nitrosocysteine and
      nitrotyrosine residues were detected in regions of the epiphysis with the highest
      levels of NOS expression. Maturing chick sternal chondrocytes evidenced an
      increase in NO release and a rise in NOS protein levels. When treated with NOS
      inhibitors, there was a decrease in the alkaline phosphatase activity of the
      hypertrophic cells. On the other hand, NO donors caused a small but significant
      elevation in alkaline phosphatase activity. Transient transfections of
      chondrocytes with an endothelial NOS isoform caused an increase in collagen type
      X promoter activity. Induction of both collagen type X expression and alkaline
      phosphatase activity was blocked by inhibitors of the cGMP pathway. These
      findings indicate that NO is generated by three NOS isoforms in terminally
      differentiated chondrocytes. The expression of NOS and the generation of NO
      enhanced maturation by upregulating alkaline phosphatase and collagen type X
      expression. Since expression of these two determinants was blocked by inhibitors
      of the cGMP pathway, it is concluded that NO metabolism is required for
      development of the mature chondrocyte phenotype.

PMID- 15869915
TI  - Ectopic bone formation by microporous calcium phosphate ceramic particles in
      sheep muscles.
AB  - Calcium phosphate ceramics are widely used in bone reconstructive surgery because
      of their osteconductive properties. However, these materials generally lack
      osteoinductive properties required to support bone healing in large defects. In
      this article, we study the osteoinductive potential of calcium phosphate ceramic
      particles implanted for 6 months into the dorsal muscles of eight adult female
      sheep. Microporous biphasic calcium phosphate (MBCP) granules of 1-2 mm composed
      of hydroxyapatite and beta-tricalcium phosphate (60/40) had macropores of 450
      microm, micropores of 0.43 microm, and a specific surface area of 1.8 m(2)/g.
      After 6 months in the back muscles of sheep, the explants composed of MBCP
      granules were hard and encapsulated by normal muscle tissue. Ectopic bone
      formation with Haversian structures was observed in close contact with the MBCP
      granules in histological sections. Back-scattered electron microscopy and micro
      computed tomography indicated that approximately 10% of well-mineralized bone
      with mature osteocytes had formed between or upon the granules. The ectopic bone
      showed trabeculae bridging the MBCP granules. Both the number and thickness of
      the trabeculae formed between the MBCP particles were comparable to those
      measured in spongious bone. The overall results therefore confirmed the presence
      of mature bone after intramuscular implantation of MBCP granules. The different
      hypotheses explaining ectopic bone formation induced by MBCP granules are
      discussed. Synthetic bone substitutes with osteoinductive properties could be
      used in bone reconstructive surgery.

PMID- 15869917
TI  - In vivo short-term precision of hip structure analysis variables in comparison
      with bone mineral density using paired dual-energy X-ray absorptiometry scans
      from multi-center clinical trials.
AB  - Hip structural analysis (HSA) is a technique for extracting strength-related
      structural dimensions of bone cross-sections from two-dimensional hip scan images
      acquired by dual energy X-ray absorptiometry (DXA) scanners. Heretofore the
      precision of the method has not been thoroughly tested in the clinical setting.
      Using paired scans from two large clinical trials involving a range of different
      DXA machines, this study reports the first precision analysis of HSA variables,
      in comparison with that of conventional bone mineral density (BMD) on the same
      scans. A key HSA variable, section modulus (Z), biomechanically indicative of
      bone strength during bending, had a short-term precision percentage coefficient
      of variation (CV%) in the femoral neck of 3.4-10.1%, depending on the
      manufacturer or model of the DXA equipment. Cross-sectional area (CSA), a
      determinant of bone strength during axial loading and closely aligned with
      conventional DXA bone mineral content, had a range of CV% from 2.8% to 7.9%.
      Poorer precision was associated with inadequate inclusion of the femoral shaft or
      femoral head in the DXA-scanned hip region. Precision of HSA-derived BMD varied
      between 2.4% and 6.4%. Precision of DXA manufacturer-derived BMD varied between
      1.9% and 3.4%, arising from the larger analysis region of interest (ROI). The
      precision of HSA variables was not generally dependent on magnitude, subject
      height, weight, or conventional femoral neck densitometric variables. The
      generally poorer precision of key HSA variables in comparison with conventional
      DXA-derived BMD highlights the critical roles played by correct limb
      repositioning and choice of an adequate and appropriately positioned ROI.

PMID- 15869916
TI  - Fluid flow stimulates expression of osteopontin and bone sialoprotein by bone
      marrow stromal cells in a temporally dependent manner.
AB  - Bone marrow stromal cells (BMSCs) are multipotent progenitor cells with a
      capacity to form bone tissue in vivo, and to differentiate into the osteoblastic
      lineage in vitro. Drawing on evidence that bone is mechanosensitive and
      mechanical stimuli are anabolic, we postulate that proliferation and osteoblastic
      differentiation of BMSCs may be stimulated by mechanical forces. In this study,
      BMSCs cultured in the presence of osteogenic factors (dexamethasone, beta
      glycerophosphate, and ascorbate) were stimulated repeatedly (every second day)
      with shearing flow (1.6 dyn/cm(2)) for 5, 30, or 120 min, and assayed for
      systematic changes in cell number and phenotypic markers of osteoblastic
      differentiation. Cells exposed to fluid flow on days 2 and 4 after the addition
      of osteogenic factors and assayed at day 6 exhibited a modest decrease in cell
      number and increase in normalized alkaline phosphatase activity, suggesting the
      detachment of a non-osteogenic subpopulation. Cells exposed to fluid flow on days
      6, 8, 10, and 12 and assayed at day 20 demonstrated maximal expression of
      osteopontin and bone sialoprotein mRNA with 30 min duration of flow.
      Concurrently, at day 20 expression of the adipogenic marker, lipoprotein lipase,
      was minimal with a 120-min duration of flow. These results indicate that repeated
      application of shear stress stimulates late phenotypic markers of osteoblastic
      differentiation of BMSCs in a manner that depends on the duration of stimulus.
      Finally, accumulation of prostaglandin E(2) in culture medium in response to
      shearing flow systematically decreased with repeated exposure to 30 and 120 min
      of shear stress (from day 6 to day 12), suggesting an adaptation of the cells to
      fluid flow.

PMID- 15869918
TI  - Complementary antagonistic actions between C-type natriuretic peptide and the
      MAPK pathway through FGFR-3 in ATDC5 cells.
AB  - We previously reported that C-type natriuretic peptide (CNP) stimulates
      endochondral ossification and corrects the reduction in body length of
      achondroplasia model mouse with constitutive active fibroblast growth factor
      receptor 3 (FGFR-3). In order to examine the interaction between CNP and FGFR-3,
      we studied intracellular signaling by using ATDC5 cells, a mouse chondrogenic
      cell line, and found that FGF2 and FGF18 markedly reduced CNP-dependent
      intracellular cGMP production, and that these effects were attenuated by MAPK
      inhibitors. Western blot analysis demonstrated that the level of GC-B, a
      particulate guanylyl cyclase specific for CNP, was not changed by treatment with
      FGFs. Conversely, CNP and 8-bromo-cGMP strongly and dose-dependently inhibited
      the induction of ERK phosphorylation by FGF2 and FGF18 without changing the level
      of FGFR-3, although they did not affect the phosphorylation of STAT-1. In the
      organ-cultured fetal mouse tibias, CNP and FGF18 counteracted on the longitudinal
      bone growth, and both the size and number of hypertrophic chondrocytes. The
      FGF/FGFR-3 pathway is known as the negative regulator of endochondral
      ossification. We found that FGFs inhibited CNP-stimulated cGMP production by
      disrupting the signaling pathway through GC-B while CNP antagonized the
      activation of the MAPK cascade by FGFs. These results suggest that the CNP/GC-B
      pathway plays an important role in growth plate chondrocytes and constitutes the
      negative cross talk between FGFs and the activity of MAPK. Our results may
      explain one of the molecular mechanisms of the growth stimulating action of CNP
      and suggest that activation of the CNP/GC-B pathway may be effective as a novel
      therapeutic strategy for achondroplasia.

PMID- 15869919
TI  - Varying contributions of growth and ageing to racial and sex differences in
      femoral neck structure and strength in old age.
AB  - The structural basis of racial and sex differences in femoral neck (FN) fragility
      in old age was assessed in a cross-sectional study of 829 healthy Chinese and
      1181 healthy Caucasian subjects aged 18 to 93 years in Melbourne, Australia. We
      measured FN bone mineral density (BMD), periosteal diameter, and estimated
      endocortical diameter, cortical thickness, volumetric BMD (vBMD), section
      modulus, and buckling ratio using dual X-ray absorptiometry. Racial and sex
      differences in structural and strength indices were adjusted for age, bone length
      and body weight and were expressed in standard deviation (SD) unit. In young
      adulthood, Chinese women had a 0.85 SD narrower FN, a 0.47 SD thinner cortex and
      a 0.79 SD shorter FN axis length (FNAL) than Caucasian women. Across age, Chinese
      and Caucasian women had similar increments in endocortical and periosteal
      diameters and similar decrements in cortical thickness and vBMD (both
      approximately 20%). In young adult males, FN periosteal diameter did not differ
      by race, but cortical thickness was 0.35 SD lower in Chinese than Caucasians.
      Across age, increments in periosteal and endocortical diameters were less in
      Chinese than Caucasian men so cortical thickness and vBMD diminished less in
      Chinese than in Caucasian men. In both races, young adult women had narrower FN
      than men. As Chinese women had a greater increment in periosteal diameter than
      Chinese men across age, the sex difference in FN periosteal diameter established
      in young adulthood diminished in old age. As Caucasian men had a greater
      increment in periosteal diameter than Caucasian women, the sex difference in FN
      periosteal diameter established in young adulthood increased with age. In old
      age, for both sexes, Chinese had a higher fracture risk in bending than
      Caucasians, but a lower fracture risk by buckling. For both races, women had a
      higher fracture risk in bending than men. Racial and sexual dimorphism in the
      absolute and relative behavior of the periosteal and endocortical surfaces
      throughout life produce race- and sex-specific differences in FN size, cortical
      thickness, and indices of bone strength in old age.

PMID- 15869920
TI  - Combined treatment with PTH (1-34) and OPG increases bone volume and uniformity
      of mineralization in aged ovariectomized rats.
AB  - The combination of PTH with OPG has been proposed as a potential therapy in
      patients with severe osteoporosis. In the present study, we examined the bone
      material of aged ovariectomized (OVX) rats treated either with PTH (1-34) or OPG
      alone or in combination of both. The micro- and nanostructural characteristics of
      the mineralized bone were evaluated using quantitative backscattered electron
      imaging (qBEI) and small-angle X-ray scattering (SAXS). Rats (n=68) were either
      sham-operated or ovariectomized (OVX) at the age of 3 months, and 15 months
      later, OVX animals were treated either with vehicle, OPG (10 mg/kg), PTH (80
      microg/kg) or a combination of both during 5.5 months. All treatments were by
      subcutaneous injection, 3 days per week. Secondary metaphyseal spongiosa from
      distal femora was assessed for mineralized bone volume (BV/TV), for the mean Ca
      concentration (Camean), the width of the bone mineralization density distribution
      (Cawidth), as well as the average mineral particle thickness parameter (T) and
      the degree of alignment of the mineral particles (rho). A remarkable increase of
      BV/TV up to 139% (P<0.001) was observed in the PTH-treated groups independently
      of OPG. Camean was slightly increased (+1.7%, P<0.05) in the OPG-treated group.
      Cawidth was reduced (-6.4%, P<0.01, and -8.9%, P<0.001) in animals treated with
      OPG and PTH+OPG, respectively. In contrast, Cawidth in sham-operated rats was
      16.0% (P<0.001) higher than in OVX. The T parameter was not altered in the
      trabecular bone within the group of treated and untreated OVX rats. However, the
      non-ovariectomized animals exhibited a significantly lower T value (-7.1%,
      P<0.01) with respect to OVX. In conclusion, qBEI and SAXS data of OVX rats
      suggest that PTH alone was responsible for increase of bone volume, whereas OPG
      positively influenced the homogeneity and density of mineralization without
      affecting the nanostructure of the bone material.

PMID- 15869921
TI  - Quantification of metaphyseal modeling in children treated with bisphosphonates.
AB  - There has been recent concern in the literature that the treatment with
      bisphosphonates in children can have an adverse effect on metaphyseal modeling
      leading to "drug-induced osteopetrosis". We created a normal database called
      metaphyseal index in the distal femur so that we could quantify the inwasting
      modeling process in children on bisphosphonates. Radiographs of the distal femur
      of 468 normal children who had presented to our institution for orthopedic trauma
      were examined. A measurement of the distal femoral growth plate width (GPW) was
      recorded. The femoral width at an interval of 0.5 GPW proximal to the distal
      femoral growth plate was also recorded (0.5 W). The metaphyseal index was defined
      as a ratio of 0.5 W/GPW. A graph of the means, one and two standard deviations
      from the mean, was constructed using the data obtained from this cohort. We found
      this ratio to be constant with minimal variability regardless of the age or sex
      of the child. We plotted 20 patients at our institution given bisphosphonates for
      localized orthopedic complaints. Z scores for girls averaged 0.68 and boys 0.13.
      Three patients had Z scores >2.0, with values of 2.2, 2.9, and 3.2. Metaphyseal
      modeling in the distal femur is constant, with slight variation between sexes,
      resulting in a similar shape of the distal femur throughout childhood. Clinically
      relevant doses of bisphosphonates given for appropriate indications do not
      necessarily disturb this process, while the beneficial clinical effect is
      maintained.

PMID- 15869922
TI  - Local application of rhTGF-beta2 enhances peri-implant bone volume and bone
      implant contact in a rat model.
AB  - Orthopedic and dental implant fixation depends upon bone regeneration. Growth
      factors such as transforming growth factor-beta (TGF-beta) have been shown to
      enhance bone repair and strengthen the mechanical connection between implant and
      host skeleton in canine models. To provide a platform for studying molecular
      mechanisms of growth factor stimulated bone regeneration and implant fixation,
      the present study examined peri-implant bone volume as a response to TGF-beta
      treatment in a rodent model. The rat femoral ablation model in which an implant
      is placed in the medullary cavity of the femur was used to examine the dose
      response to TGF-beta2 applied to the implant (0, 0.1, 1.0, or 10 microg). The
      study included a total of 40 rats (10 per dose) examined at 28 days. Peri-implant
      bone volume and bone-implant contact were assessed through microcomputed
      tomography and implant fixation strength was determined by a mechanical pullout
      test. Treatment of the implant with 10 microg TGF-beta2 led to a 2-fold increase
      in bone volume (P<0.001) and a 1.5-fold increase in bone-implant contact (P<0.01)
      with a trend of increasing fixation strength (non-significant increase of 1.4
      fold). TGF-beta2 treatment with 10 microg led to uniform peri-implant bone volume
      and bone-implant contact along the length of the implant, whereas the other
      groups had less bone at the mid-point compared to the proximal and distal aspects
      of the implant. About 50% of the variance in implant fixation strength was
      explained by a regression model involving both bone-implant contact and peri
      implant bone volume.

PMID- 15869923
TI  - Structural and biomechanical basis of racial and sex differences in vertebral
      fragility in Chinese and Caucasians.
AB  - We conducted a cross-sectional study in 1868 healthy Chinese and Caucasian women
      and men aged 18 to 93 years to define the structural and biomechanical basis for
      racial and sex differences in vertebral body (VB) fragility. VB bone mineral
      content (BMC), cross-sectional area (CSA), and volumetric bone mineral density
      (vBMD) of the third lumbar vertebrae were measured using dual-energy X-ray
      absorptiometry. Using engineering principles, we calculated the load per unit CSA
      (stress), VB strength estimated from vBMD and the ratio of stress to strength
      (fracture risk index, FRI). Young adult Chinese women and men had a smaller VB
      with a higher vBMD than their Caucasian counterparts. In each race, women had a
      smaller VB than men but similar vBMD. From young adulthood ( approximately 30
      years) to old age ( approximately 70 years), VB CSA increased more in Chinese
      than Caucasian women (8.6% vs. 5.8%) and increased less in Chinese than Caucasian
      men (8.7% vs. 11.8%). Estimated periosteal bone deposited was similar in Chinese
      and Caucasian women (2.64 vs. 2.63 g, 46% vs. 40% of peak BMC). Estimated
      endosteal bone lost was similar (3.94 vs. 4.05 g or 68% vs. 62% of peak BMC). As
      endosteal bone loss exceeded periosteal bone gain, net bone was lost from the VB,
      but this was similar in Chinese and Caucasian women (1.30 vs. 1.42 g or both lost
      22% of peak BMC). For men, Chinese gained less periosteal bone than Caucasians
      (2.73 vs. 5.05 g or 34% vs. 56% of peak BMC) and lost less endosteal bone (3.07
      vs. 5.49 g or 38% vs. 61% of peak BMC), so net bone loss was similar in Chinese
      and Caucasian men (0.34 vs. 0.44 g, both lost 5% of peak BMC). Comparing sexes,
      in Chinese, net bone loss was greater in women than in men because of greater
      endosteal bone loss in women (68% of peak BMC) than men (38% of peak BMC);
      periosteal bone gain was similar in women and men. In Caucasians, net bone loss
      was greater in women than men because periosteal bone gain was less in women
      (40%) than men (56%), endosteal bone loss was similar. The age-related increase
      in VB CSA reduced VB stress but vBMD decreased so the FRI increased;
      approximately 25% of elderly Chinese and Caucasian women and approximately 5% of
      elderly Chinese and Caucasian men had an FRI above unity. The structural basis of
      bone fragility differs by race and sex. Periosteal apposition plays a pivotal
      role in determining racial and sex differences in net bone loss, geometry, and
      strength.

PMID- 15869924
TI  - A generalized skeletal hyperostosis in two siblings caused by a novel mutation in
      the SOST gene.
AB  - In this study, a brother and sister of German origin are described with a
      possible diagnosis of van Buchem disease, a rare autosomal recessive sclerosing
      bone dysplasia characterized by a generalized hyperostosis of the skeleton mainly
      affecting the cranial bones. Clinically, patients suffer from cranial nerve
      entrapment potentially resulting in facial paresis, hearing disturbances, and
      visual loss. The radiological picture of van Buchem disease closely resembles
      sclerosteosis, although in the latter patients, syndactyly, tall stature, and
      raised intracranial pressure are frequently observed, allowing a differential
      diagnosis with van Buchem disease. Previous molecular studies demonstrated
      homozygous loss-of-function mutations in the SOST gene in sclerosteosis patients
      while a chromosomal rearrangement creating a 52-kb deletion downstream of this
      gene was found in Dutch patients with van Buchem disease. This deletion most
      likely suppresses SOST expression. Sclerostin, the SOST gene product, has been
      shown to play a role in bone metabolism. The two siblings reported here were
      evaluated at the molecular level by carrying out a mutation analysis of the SOST
      gene. This resulted in the identification of a novel putative disease-causing
      splice site mutation (IVS1 + 1 G-->C) homozygously present in both siblings.

PMID- 15869925
TI  - Bone calcium changes during diabetic ketoacidosis: a comparison with lactic
      acidosis due to volume depletion.
AB  - In this study, we aimed to compare bone calcium system changes from children with
      diabetic ketoacidosis or acute metabolic acidosis due to dehydration to find out
      the relative contribution of metabolic acidosis and diabetes-related factors on
      expected negative calcium balance. We studied a set of non-invasive parameters of
      bone remodeling in 16 children with diabetic ketoacidosis due to new onset type 1
      diabetes and 25 children with acute metabolic acidosis due to dehydration
      complicating acute gastroenteritis before and after the correction of acidosis.
      The two groups of subjects were matched for age, sex, pubertal status, and degree
      of metabolic acidosis and dehydration. A group of 18 age and sex-matched healthy
      children served as the control group. Plasma ionized calcium levels were
      increased in both groups, significantly more so in diabetic ketoacidosis. While
      osteoblastic markers, osteocalcin and alkaline phosphatase, were depressed to a
      comparable degree in both groups, urinary calcium/creatinine ratio and
      hydroxyproline excretion were significantly greater in diabetic ketoacidosis. No
      significant changes in calcitrophic hormone (intact PTH, calcitonin, 25-hydroxy
      vitamin D3) levels were observed. All study parameters except for serum phosphate
      levels behaved in parallel in both clinical conditions, and abnormalities
      disappeared with the correction of acidosis except for IGF-1, which remained low
      in diabetic subjects. In conclusion, our results suggest that, in diabetic
      ketoacidosis, the observed severe negative calcium balance occurred through
      diminished bone formation mediated by metabolic acidosis per se and increased
      bone mineral dissolution and bone resorption because of severe insulin deficiency
      and secondarily via metabolic acidosis. Observed changes appear to be independent
      of calcitrophic hormones.

PMID- 15869926
TI  - Genetic dissection of phosphate- and vitamin D-mediated regulation of circulating
      Fgf23 concentrations.
AB  - Fibroblast growth factor-23 (FGF23) is a circulating factor that plays critical
      roles in phosphate and vitamin D metabolism. The goal of our studies was to
      dissect the pathways directing the vitamin D-phosphate-FGF23 homeostatic axis. To
      test the role of diet in the regulation of Fgf23, wild-type (WT) mice were fed
      either a standard (0.44% phosphorus) or a low-phosphate (0.02%) diet. WT mice on
      standard diet had a serum phosphate of 9.5 +/- 0.3 mg/dl and an Fgf23
      concentration of 99.0 +/- 10.6 pg/ml; mice on the low-phosphate diet had a
      phosphate of 5.0 +/- 0.2 mg/dl (P < 0.01) and an Fgf23 of 10.6 +/- 3.7 pg/ml (P <
      0.01). To genetically separate the effects of phosphate and vitamin D on Fgf23,
      we examined vitamin D receptor null (VDR(-/-)) mice, which are hypocalcemic and
      hypophosphatemic secondary to hyperparathyroidism. On standard diets, WT and
      VDR(+/-) mice had Fgf23 levels of 106.0 +/- 30.7 and 90.6 +/- 17.3 pg/ml,
      respectively, whereas Fgf23 was undetectable in the VDR(-/-). Animals were then
      placed on a diet that normalizes serum calcium and phosphorus. This 'rescue'
      increased Fgf23 in WT to 192.3 +/- 32.5 pg/ml and in VDR(+/-) to 388.2 +/-
      89.6pg/ml, and importantly, in VDR(-/-) to 476.9 +/- 60.1 pg/ml (P < 0.01 vs.
      WT). In addition, renal vitamin D 1-alpha hydroxylase (1alpha-OHase) mRNA levels
      were corrected to WT levels in the VDR(-/-) mice. In summary, Fgf23 is suppressed
      in diet-induced hypophosphatemia and in hypophosphatemia associated with
      secondary hyperparathyroidism. Normalization of serum phosphate by diet in VDR(-/
      ) mice increases Fgf23. Thus, our results demonstrate that Fgf23 is independently
      regulated by phosphate and by vitamin D.

PMID- 15869927
TI  - Muscle strength is a determinant of bone mineral content in the hemiparetic upper
      extremity: implications for stroke rehabilitation.
AB  - Individuals with stroke have a high incidence of bone fractures and approximately
      30% of these fractures occur in the upper extremity. The high risk of falls and
      the decline in bone and muscle health make the chronic stroke population
      particularly prone to upper extremity fractures. This was the first study to
      investigate the bone mineral content (BMC), bone mineral density (BMD), and soft
      tissue composition of the upper extremities and their relationship to stroke
      related impairments in ambulatory individuals with chronic stroke (onset >1
      year). Dual-energy X-ray absorptiometry (DXA) was used to acquire total body
      scans on 56 (22 women) community-dwelling individuals (>or=50 years of age) with
      chronic stroke. BMC (g) and BMD (g/cm2), lean mass (g), and fat mass (g) for each
      arm were derived from the total body scans. The paretic upper extremity was
      evaluated for muscle strength (hand-held dynamometry), impairment of motor
      function (Fugl-Meyer motor assessment), spasticity (Modified Ashworth Scale), and
      amount of use of the paretic arm in daily activities (Motor Activity Log).
      Results showed that the paretic arm had significantly lower BMC (13.8%, P<0.001),
      BMD (4.5%, P<0.001), and lean mass (9.0%, P<0.001) but higher fat mass (6.3%,
      P=0.028) than the non-paretic arm. Multiple regression analysis showed that lean
      mass in the paretic arm, height, and muscle strength were significant predictors
      (R2=0.810, P<0.001) of the paretic arm BMC. Height, muscle strength, and gender
      were significant predictors (R2=0.822, P<0.001) of lean mass in the paretic arm.
      These results highlight the potential of muscle strengthening to promote bone
      health of the paretic arm in individuals with chronic stroke.

PMID- 15869928
TI  - The effect of bone loss on rod-like and plate-like trabeculae in the cancellous
      bone of the mandibular condyle.
AB  - Bone loss may affect the structure of cancellous bone. But its effect on
      trabeculae with different characteristics, like rods and plates, is not
      accurately known. This study analyzes the effect of bone loss on individual rod
      like and plate-like trabeculae. 94 specimens were obtained from mandibular
      condyles from both dentate and edentate humans and scanned with a micro-CT
      scanner. The bone volume fraction (BV/TV) of these specimens ranged from 7% to
      30%. Next, the rod-like and plate-like trabeculae were identified with an
      especially developed algorithm. Plate volume fraction (PV/TV), rod volume
      fraction (RV/TV), plate thickness, rod thickness, number of plates, and number of
      rods were determined. In individual specimens, the thickness of the rods ranged
      from 40 mum to 180 mum, while the thickness of the plates ranged from 40 mum to
      300 mum. In every specimen, the thickness of the plates was larger than the
      thickness of the rods. Statistical analysis revealed that PV/TV was proportional
      (r = 0.98, P < 0.001) and RV/TV inversely proportional (r = -0.45, P < 0.001) to
      BV/TV. Also the thickness of the plates correlated with BV/TV (r = 0.62, P <
      0.001), while the thickness of the rods (mean = 90 mum, SD = 7 mum) remained
      constant (r = -0.09, P = 0.378). A four-fold reduction of the bone volume
      fraction was accompanied by a three-fold reduction of the number of plates and a
      40% reduction of their thickness, but also by a three-fold increase in the number
      of rods and RV/TV. It was concluded that the effect of bone loss on plate-like
      trabeculae was opposite to its effect on rod-like trabeculae. Remarkably, the
      thickness of the rods (90 mum) was independent of the bone volume fraction. This
      suggests that there is a minimal thickness for trabeculae.

PMID- 15869929
TI  - Osteopenia and impaired fracture healing in aged EP4 receptor knockout mice.
AB  - The EP4 receptor, one of the subtypes of the prostaglandin E2 (PGE2) receptor,
      plays a critical role in the anabolic effects of PGE2 on bone. However, its role
      in the maintenance of bone mass in aged animals and its role in fracture healing
      is not well known. Our studies addressed these issues by characterizing the
      skeletal phenotype of aged, EP4 receptor knockout (KO) mice, and by comparing
      fracture healing in aged KO mice versus wild type (WT) mice. There was no
      significant difference in body weight and femoral length between KO and WT mice
      at 15 to 16 months of age. Lower bone mass was seen radiographically in both
      axial and long bones of KO mice relative to WT mice. Micro-CT images of the
      distal femurs showed thinner cortices, fewer trabeculae, and a deteriorated
      trabecular network in KO mice. Total bone content, trabecular content, and
      cortical content, as assessed by pQCT in the distal femur, were lower in KO mice
      than WT controls. Histomorphometric measurements showed that trabecular bone
      volume and bone formation rate were significantly decreased whereas osteoclast
      number on trabecular surface and eroded surface on endocortical surface were
      significantly increased in KO mice. These data indicated that deleting the EP4
      receptor resulted in an imbalance in bone resorption over formation, leading to a
      negative bone balance. The lower bone formation rate in EP4 KO mice was primarily
      due to decreased mineralizing surface, suggesting that the defect in overall bone
      formation was mainly due to the defect in osteoblastogenesis. Fracture healing
      was examined in KO and WT mice subjected to a transverse femoral fracture. Callus
      formation was significantly delayed as evidenced both radiographically and
      histologically in the fractured femurs of KO mice compared with those of WT mice.
      KO mice had significant decreases in total callus area, cartilaginous callus
      area, and bony callus area 2 weeks after fracture. By 4 weeks, complete bony
      bridging was seen in WT mice but not in KO mice. These data demonstrate that the
      absence of the EP4 receptor decreases bone mass and impairs fracture healing in
      aged male mice. Our findings indicate that the EP4 receptor is a positive
      regulator in the maintenance of bone mass and fracture healing.

PMID- 15869930
TI  - Directing stem cells and progenitor cells on the stage of spinal cord injury.

PMID- 15869931
TI  - Can bone marrow-derived stem cells differentiate into functional neurons?

PMID- 15869932
TI  - Oxidative stress and inflammation in Parkinson's disease: is there a causal link?
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by a
      dramatic loss of dopaminergic neurons in the substantia nigra (SN). Among the
      many pathogenic mechanisms thought to contribute to the demise of these cells,
      dopamine-dependent oxidative stress has classically taken center stage due to
      extensive experimental evidence showing that dopamine-derived reactive oxygen
      species and oxidized dopamine metabolites are toxic to nigral neurons. In recent
      years, however, the involvement of neuro-inflammatory processes in nigral
      degeneration has gained increasing attention. Not only have activated microglia
      and increased levels of inflammatory mediators been detected in the striatum of
      deceased PD patients, but a large body of animal studies points to a contributory
      role of inflammation in dopaminergic cell loss. Recently, postmortem examination
      of human subjects exposed to the parkinsonism-inducing toxin, 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP), revealed the presence of activated microglia
      decades after drug exposure, suggesting that even a brief pathogenic insult can
      induce an ongoing inflammatory response. Perhaps not surprisingly, non-steroidal
      anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of developing
      PD. In the past few years, various pathways have come to light that could link
      dopamine-dependent oxidative stress and microglial activation, finally ascribing
      a pathogenic trigger to the chronic inflammatory response characteristic of PD.

PMID- 15869933
TI  - Growth-associated gene expression after stroke: evidence for a growth-promoting
      region in peri-infarct cortex.
AB  - Stroke induces axonal sprouting in peri-infarct cortex. A set of growth
      associated genes important in axonal sprouting in peripheral nervous system
      regeneration and cortical development has recently been defined. The expression
      profiles of these growth-associated genes were defined during the post-stroke
      axonal sprouting response using a model of stroke in barrel field cortex. Stroke
      induces sequential waves of neuronal growth-promoting genes during the sprouting
      response: an early expression peak (SPRR1), a mid expression peak (p21, Ta1
      tubulin, L1, MARCKS), a late peak (SCG10, SCLIP), and an early/sustained pattern
      (GAP43, CAP23, c-jun). These expression peaks correspond to specific time points
      in the sprouting response. The expression of the growth-inhibiting chondroitin
      sulfate proteoglycans aggrecan, brevican, versican, and phosphacan are induced
      late in the sprouting process; except neurocan, which is increased during the
      peak of the growth-promoting gene expression. The developmentally associated
      growth inhibitors ephrin-A5, ephB1, semaphorin IIIa, and neuropilin 1 are also
      induced in the early phases of the sprouting response. At the cellular level,
      chondroitin sulfate proteoglycans, in the form of peri-neuronal nets, are reduced
      in the region of axonal sprouting, during the peak of growth-promoting gene
      expression. These results identify a unique profile of growth-promoting gene
      expression in adult cortex after stroke, the inhibitory molecules that are
      present during the sprouting response, and a region in which growth-promoting
      genes are increased, growth-inhibitory proteins are diminished and axonal
      sprouting occurs. This region may be a growth-promoting zone after stroke.

PMID- 15869934
TI  - Neuro-glial differentiation of human bone marrow stem cells in vitro.
AB  - Bone marrow (BM) is a rich source of stem cells and may represent a valid
      alternative to neural or embryonic cells in replacing autologous damaged tissues
      for neurodegenerative diseases. The purpose of the present study is to identify
      human adult BM progenitor cells capable of neuro-glial differentiation and to
      develop effective protocols of trans-differentiation to surmount the
      hematopoietic commitment in vitro. Heterogeneous cell populations such as whole
      BM, low-density mononuclear and mesenchymal stem (MSCs), and several
      immunomagnetically separated cell populations were investigated. Among them, MSCs
      and CD90+ cells were demonstrated to express neuro-glial transcripts before any
      treatment. Several culture conditions with the addition of stem cell or
      astroblast conditioned media, different concentrations of serum, growth factors,
      and supplements, used alone or in combinations, were demonstrated to alter the
      cellular morphology in some cell subpopulations. In particular, MSCs and CD90+
      cells acquired astrocytic and neuron-like morphologies in specific culture
      conditions. They expressed several neuro-glial specific markers by RT-PCR and
      glial fibrillary acid protein by immunocytochemistry after co-culture with
      astroblasts, both in the absence or presence of cell contact. In addition,
      floating neurosphere-like clones have been observed when CD90+ cells were grown
      in neural specific media. In conclusion, among the large variety of human adult
      BM cell populations analyzed, we demonstrated the in vitro neuro-glial potential
      of both the MSC and CD90+ subset of cells. Moreover, unidentified soluble factors
      provided by the conditioned media and cellular contacts in co-culture systems
      were effective in inducing the neuro-glial phenotype, further supporting the
      adult BM neural differentiative capability.

PMID- 15869935
TI  - Xenografted fetal dorsal root ganglion, embryonic stem cell and adult neural stem
      cell survival following implantation into the adult vestibulocochlear nerve.
AB  - Sensorineural hearing loss is a disabling condition. In the post-embryonic and
      adult mammalian inner ear, the regeneration of auditory hair cells, spiral
      ganglion neurons or their axons does not occur naturally. This decrease in
      excitable neurons limits the success of auditory rehabilitation. Allografts and
      xenografts have shown promise in the treatment of a variety of neurological
      diseases. Fetal dorsal root ganglion (DRG) neurons can extend functional
      connections in the rat spinal cord. Embryonic stem cells (ES cells) and adult
      neural stem cells (ANSC) have the potential to differentiate into neurons. We
      have implanted embryonic days (E) 13-16 fetal mouse DRGs from transgenic mouse
      lines that express Enhanced Green Fluorescent Protein (EGFP) or lacZ reporter
      genes, EGFP-expressing ES cells or lacZ-expressing ANSC into the injured
      vestibulocochlear nerve of adult rats and guinea pigs. Survival of the implants
      was assessed 2 to 4 weeks postoperatively. For further evaluation of the
      differentiation of the implanted ES-cells, we double labeled with the mouse
      specific neuronal antibody Thy 1.2. The rats implanted with EGFP- or lacZ
      expressing DRGs showed labeled DRGs after sacrifice. In addition, EGFP-positive
      nerve fibers were seen growing within the proximal nerve. The results from the
      EGFP ES cells and lacZ ANSC revealed reporter-expressing cells at the site of
      injection in the vestibulocochlear nerve of the host rats and guinea pigs but
      also within the brain stem. Thy 1.2 profiles were seen among the EGFP ES cells
      within the 8th cranial nerve. The findings of this study indicate that the
      vestibulocochlear nerve of adult rats and guinea pigs will support
      xenotransplants of embryonic DRG, ES cells and ANSC. This may have future
      clinical applicability in recreating a neuronal conduit following neuronal injury
      between the inner ear and the central nervous system (CNS).

PMID- 15869936
TI  - Structural and functional alterations of spinal cord axons in adult Long Evans
      Shaker (LES) dysmyelinated rats.
AB  - Abnormal formation or loss of myelin is a distinguishing feature of many
      neurological disorders and contributes to the pathobiology of neurotrauma. In
      this study we characterize the functional and molecular changes in CNS white
      matter in Long Evans Shaker (LES) rats. These rats have a spontaneous mutation of
      the gene encoding myelin basic protein which results in severe dysmyelination of
      the central nervous system (CNS), providing a unique model for
      demyelinating/dysmyelinating disorders. To date, the functional and molecular
      changes in CNS white matter in this model are not well understood. We have used
      in vivo somatosensory evoked potential (SSEP), in vitro compound action potential
      (CAP) recording in isolated dorsal columns, confocal immunohistochemistry,
      Western blotting and real-time PCR to examine the electrophysiological, molecular
      and cellular changes in spinal cord white matter in LES rats. We observed that
      dysmyelination is associated with dispersed labeling of Kv1.1 and Kv1.2 K+
      channel subunits, as well as Caspr, a protein normally confined to paranodes,
      along the LES rat spinal cord axons. Abnormal electrophysiological properties
      including attenuation of CAP amplitude and conduction velocity, high frequency
      conduction failure and enhanced sensitivity to K+ channel blockers 4
      aminopyridine and dendrotoxin-I were observed in spinal cord axons from LES rats.
      Our results in LES rats clarify some of the key molecular, cellular and
      functional consequences of dysmyelination and myelin-axon interactions. Further
      understanding of these issues in this model could provide critical insights for
      neurological disorders characterized by demyelination.

PMID- 15869937
TI  - The p53-independent nuclear translocation of cyclin G1 in degenerating neurons by
      ischemic and traumatic insults.
AB  - Cyclin G1 (CG1) was identified as a p53-transactivated target gene, and yet its
      physiological and pathological roles have been unclear. Here, we demonstrate that
      CG1 is translocated from cytoplasm to the nuclei of neurons in response to
      variety of injuries. In the normal matured rodent brain, CG1 immunoreactivity was
      hardly observed; however, some brain injuries exhibited intense CG1
      immunoreactivity in the nuclei of the damaged neurons. Transient common carotid
      artery occlusion (CCAO) in the gerbil showed strong CG1-like immunoreactivity in
      the hippocampal CA1 neurons, and permanent middle cerebral artery occlusion
      (MCAO) in the mouse showed strong CG1-like immunoreactivity in the nuclei of
      neurons located in the ischemic brain regions. TUNEL staining did not exactly
      overlap with the CG1-positive cells, but overlapped highly with Fluoro-Jade B
      staining, a degeneration marker. Brain trauma caused by knife cut, cold injury,
      and kinate injection also showed CG1 accumulation in the neuronal nuclei located
      near the injury site. These observations were obtained in p53-deficient mice as
      well, suggesting that the accumulation of CG1 in the injured neurons is p53
      independent. A similar nuclear translocation of endogenous CG1 was confirmed in a
      primary culture of cortical neurons when a toxic level of N-methyl-D-aspartate
      (NMDA) was applied. These results demonstrate that nuclear translocation of CG1
      from cytoplasmic region occurs in damaged and degenerating neurons in a p53
      independent manner, and the CG1 nuclear staining could be a good marker for the
      neurons received fatal damages.

PMID- 15869938
TI  - Post-ischemic modest hypothermia (35 degrees C) combined with intravenous
      magnesium is more effective at reducing CA1 neuronal death than either treatment
      used alone following global cerebral ischemia in rats.
AB  - In this study, we investigated the efficacy of pre- and 2 h post-ischemic
      magnesium treatment with different durations of modest hypothermia (35 degrees C)
      induced immediately or 2 h following global cerebral ischemia in rats. In
      experimental group 1, rats received an intravenous loading dose (LD) of 360
      micromol/kg MgSO4 immediately before ischemia followed by a 48 h intravenous
      infusion (IVI) at 120 micromol/kg/h. Immediately post-ischemia, body temperature
      was lowered to 35 degrees C for 6 h or maintained at 37 degrees C. In
      experimental group 2, 2 h after ischemia, rats received the MgSO4 LD/IVI and/or
      had their body temperature lowered to 35 degrees C for 6, 12 or 24 h. In
      experimental group 1, ischemic rats receiving 6 h of modest hypothermia
      demonstrated 9.4% CA1 neuronal survival, whereas rats treated with magnesium
      alone or magnesium and 6 h of modest hypothermia demonstrated 5.1% and 37.9%
      neuronal survival, respectively. In experimental group 2, ischemic rats receiving
      6, 12 or 24 h of modest hypothermia demonstrated 6.1, 5 and 43% CA1 neuronal
      survival, respectively. Rats treated with magnesium and 6, 12 or 24 h of modest
      hypothermia demonstrated 8.1, 9 and 76% neuronal survival, respectively. Our
      findings demonstrate that post-ischemic treatment with a 24 h duration of modest
      hypothermia and magnesium is more effective than either treatment used alone.

PMID- 15869939
TI  - Evolution of early perihemorrhagic changes--ischemia vs. edema: an MRI study in
      rats.
AB  - OBJECTIVES: Cerebral ischemia has been proposed as a contributing mechanism to
      secondary neuronal injury after intracranial hemorrhage (ICH). The search for
      surrogate parameters that allow treatment stratification for spontaneous ICH
      continues. We aimed to examine perihemorrhagic ischemic changes with an animal
      experimental MRI study. METHODS: A high field MRI compatible setup for male
      Wistar rats was established using a double injection model. ICH was
      stereotactically placed into the right basal ganglia of 29 Wistar rats. Coronal
      T2-WI, T2*-WI and DWI were generated with a 2.35 T animal MRI scanner 15 min, 60
      min and 210 min after ICH. Clot signal characteristics, clot volumes and
      normalized ADC values were analyzed in four hematoma regions (core, periphery,
      outer rim, healthy ipsilateral tissue) in all sequences. RESULTS: T2*-WI and DWI
      reliably demonstrated ICH in 100% with only small deviation from the applied
      volume (-20% to +26%) whereas T2-WI failed to conspicuously show ICH. There were
      no perihemorrhagic ADC decreases consistent with ischemic cytotoxic edema but a
      mild vasogenic edema surrounding the ICH could be observed. CONCLUSION: T2*-WI
      and DWI are accurate for the diagnosis of hyperacute ICH. According to serial and
      crossectional ADC analysis, there is no hint towards the existence of a
      perihemorrhagic ischemic area that might be saved by early intervention. Future
      studies should focus on perfusion and metabolic/neurotoxic studies of this
      particular area and neurotoxic properties of the surrounding edema.

PMID- 15869940
TI  - Glutamate promotes NF-kappaB pathway in primary astrocytes: protective effects of
      IRFI 016, a synthetic vitamin E analogue.
AB  - Oxidative stress has been implicated in several neurodegenerative diseases
      affecting both neuronal and glial cells. The aim of this study was to investigate
      the involvement of reactive oxygen species in glutamate-evoked activation of NF
      kappaB in primary astrocytes. A prolonged exposure to glutamate (24 h) caused a
      depletion of intracellular glutathione that, in astroglial cells, has been
      considered a biochemical change typical of early astrocyte dysfunction, leading
      to cell alterations occurring in the gliosis. These effects were initiated by
      AMPA/KA receptor activation and almost completely blocked by anti-oxidants.
      Indeed, we provide evidence that the incubation of primary astrocytes with a
      hydrophilic derivative of tocopherol, such as IRFI 016, was useful to reduce
      glutamate-induced oxidative effects. This agent also reduced in a dose-dependent
      manner the nuclear translocation of both p50 and p65 subunits of NF-kappaB.
      Altogether, these data confirm that GSH content plays a pivotal role to determine
      oxidative response to glutamate injury in primary astrocyte cultures and that NF
      kappaB pathway is involved in this response. Furthermore, the positive effects
      obtained by IRFI 016 to prevent nuclear translocation of NF-kappaB may suggest
      new pharmacological strategies for antioxidant therapy and neuroprotection.

PMID- 15869941
TI  - Tumor necrosis-factor-alpha (TNF-alpha) induces rapid insertion of Ca2+-permeable
      alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)/kainate (Ca-A/K)
      channels in a subset of hippocampal pyramidal neurons.
AB  - The presence of cell surface Ca2+ permeable alpha-amino-3-hydroxyl-5-methyl-4
      isoxazole-propionate (AMPA)/kainate (Ca-A/K) channels on subsets of central
      neurons influences both normal physiological function and vulnerability to
      excitotoxicity. Factors that regulate the formation and membrane insertion of Ca
      A/K channels, however, are poorly understood. Recently, the cytokine tumor
      necrosis factor-alpha (TNF-alpha) was shown to increase the cell surface
      expression of an AMPA receptor (AMPAR) subunit (GluR1) and to potentiate
      vulnerability to AMPAR-mediated injury. In this study, we examined the
      possibility that TNF-alpha might also increase numbers of functional Ca-A/K
      channels. In acute hippocampal slice preparations, TNF-alpha appeared to increase
      Ca-A/K channel numbers in pyramidal neurons (HPNs), as assessed using a
      histochemical stain based on kainate-induced uptake of Co2+ ions (Co2+ labeling).
      In dissociated hippocampal neuronal cultures, TNF-alpha exposure (6 nM, 15 min)
      induced a rapid increase in cell surface levels not only of GluR1, but also of
      the AMPAR subunit GluR2, on most neurons, without evident new protein synthesis.
      Furthermore, consistent with the slice studies, fluorescence Ca2+ imaging
      techniques revealed an increase in numbers of Ca-A/K channels on what appeared to
      be a subset of HPNs. These observations are the first to provide evidence for the
      rapid upregulation of neuronal Ca-A/K channels in response to a cytokine or any
      other soluble factor, and provide a novel mechanism through which TNF-alpha may
      modulate both synaptic function and neuronal vulnerability.

PMID- 15869942
TI  - Embryonic radial glia bridge spinal cord lesions and promote functional recovery
      following spinal cord injury.
AB  - Radial glial cells are neural stem cells (NSC) that are transiently found in the
      developing CNS. To study radial glia, we isolated clones following
      immortalization of E13.5 GFP rat neurospheres with v-myc. Clone RG3.6 exhibits
      polarized morphology and expresses the radial glial markers nestin and brain
      lipid binding protein. Both NSC and RG3.6 cells migrated extensively in the adult
      spinal cord. However, RG3.6 cells differentiated into astroglia slower than NSC,
      suggesting that immortalization can delay differentiation of radial glia.
      Following spinal cord contusion, implanted RG3.6 cells migrated widely in the
      contusion site and into spared white matter where they exhibited a highly
      polarized morphology. When injected immediately after injury, RG3.6 cells formed
      cellular bridges surrounding spinal cord lesion sites and extending into spared
      white matter regions in contrast to GFP fibroblasts that remained in the lesion
      site. Behavioral analysis indicated higher BBB scores in rats injected with RG3.6
      cells than rats injected with fibroblasts or medium as early as 1 week after
      injury. Spinal cords transplanted with RG3.6 cells or dermal fibroblasts
      exhibited little accumulation of chondroitin sulfate proteoglycans (CSPG)
      including NG2 proteoglycans that are known to inhibit axonal growth. Reduced
      levels of CSPG were accompanied by little accumulation in the injury site of
      activated macrophages, which are a major source of CSPG. However, increased
      staining and organization of neurofilaments were found in injured rats
      transplanted with RG3.6 cells suggesting neuroprotection or regrowth. The
      combined results indicate that acutely transplanted radial glia can migrate to
      form bridges across spinal cord lesions in vivo and promote functional recovery
      following spinal cord injury by protecting against macrophages and secondary
      damage.

PMID- 15869943
TI  - Exercise restores levels of neurotrophins and synaptic plasticity following
      spinal cord injury.
AB  - We have conducted studies to determine the potential of exercise to benefit the
      injured spinal cord using neurotrophins. Adult rats were randomly assigned to one
      of three groups: (1) intact control (Con); (2) sedentary, hemisected at a mid
      thoracic level (Sed-Hx), or (3) exercised, hemisected (Ex-Hx). One week after
      surgery, the Ex-Hx rats were exposed to voluntary running wheels for 3, 7, or 28
      days. BDNF mRNA levels on the lesioned side of the spinal cord lumbar region of
      Sed-Hx rats were approximately 80% of Con values at all time points and BDNF
      protein levels were approximately 40% of Con at 28 days. Exercise compensated for
      the reductions in BDNF after hemisection, such that BDNF mRNA levels in the Ex-Hx
      rats were similar to Con after 3 days and higher than Con after 7 (17%) and 28
      (27%) days of exercise. After 28 days of exercise, BDNF protein levels were 33%
      higher in Ex-Hx than Con rats and were highly correlated (r=0.86) to running
      distance. The levels of the downstream effectors for the action of BDNF on
      synaptic plasticity synapsin I and CREB were lower in Sed-Hx than Con rats at all
      time points. Synapsin I mRNA and protein levels were higher in Ex-Hx rats than
      Sed-Hx rats and similar to Con rats at 28 days. CREB mRNA values were higher in
      Ex-Hx than Sed-Hx rats at all time points. Hemisection had no significant effects
      on the levels of NT-3 mRNA or protein; however, voluntary exercise resulted in an
      increase in NT-3 mRNA levels after 28 days (145%). These results are consistent
      with the concept that synaptic pathways under the regulatory role of BDNF induced
      by exercise can play a role in facilitating recovery of locomotion following
      spinal cord injury.

PMID- 15869944
TI  - Effect of AdGDNF on dopaminergic neurotransmission in the striatum of 6-OHDA
      treated rats.
AB  - We have previously observed that the delivery of an adenoviral vector encoding
      for glial cell line-derived neurotrophic factor (AdGDNF) into the substantia
      nigra (SN) 7 days after intrastriatal administration of 6-hydroxydopamine (6
      OHDA) protects dopamine (DA)-dependent behaviors, tyrosine hydroxylase
      immunoreactive (TH+) cells in SN, and amphetamine-induced c-fos induction in
      striatum. In the present study, we sought to determine if the behavioral
      protection observed in 6-OHDA-treated rats receiving AdGDNF was associated with
      an increase in DA availability in the striatum as measured by microdialysis. Rats
      received intrastriatal 6-OHDA (16 microg/2.8 microl) or vehicle followed 7 days
      later by intranigral AdGDNF (3.2x10(7) pfu/2 microl), AdLacZ (3.2 x 10(7) pfu/2
      microl), or phosphate buffered saline (PBS). Three weeks later, microdialysis
      samples were collected from the same striatal region under basal conditions,
      following KCl (100 mM) or amphetamine (250 microM) administered via the striatal
      microdialysis probe, or amphetamine administered systemically (6.8 mg/kg i.p).
      Animals given 6-OHDA followed by either PBS or AdLacZ showed a decrease in basal
      extracellular striatal DA levels to 24% of control. In contrast, basal
      extracellular DA in 6-OHDA-lesioned rats with a nigral injection of AdGDNF was
      almost 3-fold higher than 6-OHDA-vehicle treated animals, 65% of control DA
      levels. Moreover, although KCl and amphetamine produced no increase in striatal
      DA release in 6-OHDA-treated rats that subsequently were given either PBS or
      AdLacZ, these manipulations increased DA levels significantly in 6-OHDA-treated
      rats later given AdGDNF. Thus, DA neurotransmission within the striatum of 6-OHDA
      treated rats appears to be enhanced by increased expression of GDNF in the nigra.

PMID- 15869945
TI  - The beneficial effects of subthalamic nucleus stimulation on manipulative finger
      force control in Parkinson's disease.
AB  - We investigated the differential effects of levodopa medication and STN
      stimulation on finger force control in Parkinson subjects grasping to lift an
      object and performing vertical point-to-point movements of a hand-held object.
      The experiments were conducted in four treatment conditions: off-drug/off
      stimulation, off-drug/on-stimulation, on-drug/off-stimulation and on-drug/on
      stimulation. We found that the bradykinesia in Parkinsonian subjects improved by
      both levodopa medication and STN stimulation. As compared to healthy subjects,
      excessive grip force was observed in all Parkinson subjects, regardless of the
      treatment condition. This force excess was most pronounced in the on-drug
      condition and ameliorated by STN stimulation. We observed reliable correlations
      between the amount of force overflow and the severity of levodopa-induced
      dyskinesias in the on-drug condition. Despite some similarities regarding
      therapeutic effects on bradykinesia, our findings contrast with earlier
      observations with respect to the differential effects of levodopa and STN
      stimulation on the scaling of fingertip forces in Parkinson's disease. While
      levodopa causes an overshoot of fingertip forces, STN stimulation appears to be
      sufficient to alleviate, but not normalise the force excess. STN stimulation
      enables Parkinson subjects to scale grip force more accurately to the loads
      arising from voluntary manipulation of hand-held objects.

PMID- 15869946
TI  - Abnormal excitability in capsaicin-responsive DRG neurons from cats with feline
      interstitial cystitis.
AB  - Interstitial cystitis (IC) is a painful disorder which affects urinary bladder
      function in cats and humans. We used patch clamp techniques to measure firing
      properties and K+ currents of dorsal root ganglion (DRG) neurons (L4-S3) from
      normal cats and cats with feline interstitial cystitis (FIC) to examine the
      possibility that the properties of primary afferent neurons are changed in cats
      with FIC. We found that capsaicin (CAPS)-responsive neurons from FIC cats were
      increased in size, had increased firing in response to depolarizing current
      pulses and expressed more rapidly inactivating K+ currents. CAPS-sensitive
      neurons from FIC cats were 28% larger than those from normal cats but were
      otherwise similar with respect to membrane potential and action potential (AP)
      threshold. CAPS-responsive neurons from normal cats fired 1.5 APs in response to
      a 600 ms depolarizing current pulse, 60-200 pA in intensity. The number of APs
      was increased 4.5 fold in FIC neurons. Neurons from FIC cats also exhibited after
      hyperpolarization potentials which were on the average 2x slower than those in
      normal cat neurons. In addition, there was a lack of K+ currents in the critical
      voltage range of action potential generation (between -50 to -30 mV). These
      changes were not detected in CAPS-unresponsive neurons from normal and FIC cats.
      Our data suggest that FIC afferent neurons exhibit abnormal firing which may be
      due to changes in the behavior of K+ currents and show that these changes are
      restricted to a subpopulation of CAPS-responsive neurons.

PMID- 15869947
TI  - Effect of intrastriatal 6-OHDA lesion on dopaminergic innervation of the rat
      cortex and globus pallidus.
AB  - The present study examined in the rat the effect of a partial lesion of the
      nigrostriatal dopaminergic pathway induced by intrastriatal injection of 6
      hydroxydopamine (6-OHDA), on the dopaminergic innervation of the cortex and the
      globus pallidus as revealed using tyrosine hydroxylase (TH) immunoreactivity.
      Twenty-eight days after unilateral injection of 6-OHDA into the dorsal part of
      the striatum, TH-positive fiber density was reduced by 41% in the dorsal and
      central part of the structure, and was accompanied by a retrograde loss of 33% of
      TH-positive neurons in the substantia nigra (SN), while the ventral tegmental
      area was completely spared. In the SN, TH-positive cell loss was most severe in
      the ventral part of the structure (-55%). In the same animals, a substantial loss
      of TH-positive fibers was evident in the dorsal part of the globus pallidus, and
      involved both thick fibers of passage and thin varicose terminal axonal branches.
      In the cortex, a loss of TH-positive fibers was prominent in the cingulate area,
      moderate in the motor area and less affected in the insular area, while the
      noradrenergic innervation revealed using dopamine-beta-hydroxylase
      immunoreactivity was preserved in all of these cortical subregions. These results
      demonstrate that the intrastriatal 6-OHDA lesion model in rats produces a
      significant loss of dopaminergic axons in extrastriatal structures including the
      pallidum and cortex, which may contribute to functional sequelae in this animal
      model of Parkinson's disease.

PMID- 15869948
TI  - Chemokine- and neurotrophic factor-induced changes in E2F1 localization and
      phosphorylation of the retinoblastoma susceptibility gene product (pRb) occur by
      distinct mechanisms in murine cortical cultures.
AB  - The retinoblastoma susceptibility gene product (pRb) and E2F1 have been found to
      exhibit altered localization and increased staining in several neurodegenerative
      diseases. We have observed similar localization in primary murine cortical
      cultures treated with neurotrophic factors (NTF) or chemokines. In untreated
      cultures, E2F1 exhibited minimal immunostaining using the KH95 antibody, which
      recognizes the pRb interaction domain. In primary E16 murine cortical cultures,
      NTF- or chemokine-treated neurons, KH95 E2F1 staining was increased in the
      cytoplasm. However, an antibody recognizing the amino-terminus of E2F1 (KH20)
      stained the cytoplasm of both untreated and treated neurons. Taken together these
      results suggest that the change seen in E2F1 using the KH95 antibody is due to
      antigen unmasking of a carboxy-terminal epitope in response to NTF and
      chemokines. When we assessed staining for the hyperphosphorylated, inactive form
      of pRb (ppRb) in untreated cultures, ppRb was predominantly cytoplasmic. In
      response to NTF or chemokine treatment, staining for ppRb was observed
      predominantly in nuclei of neurons indicating a change in subcellular
      distribution. Immunoblot analysis demonstrated increased levels of ppRb in
      response to NTF and chemokines. Inhibitors of translation, nuclear export, and
      phoshpatidylinositol-3-kinase blocked NTF- and chemokine-induced nuclear ppRb
      localization while having no effect on E2F1 staining. Instead increased
      cytoplasmic KH95 E2F1 staining was dependent on cytoskeletal destabilization
      which did not influence ppRb localization. These findings demonstrate that
      alterations in ppRb distribution and E2F1 antigen availability by NTF and
      chemokines occur by distinct mechanisms suggesting that E2F1 function may be
      independent of pRb regulation in post-mitotic neurons.

PMID- 15869949
TI  - Abnormal APP, cholinergic and cognitive function in Ts65Dn Down's model mice.
AB  - We evaluated Ts65Dn Down's syndrome mice and their littermates (LM) at 1-2, 4,
      and 12 months of age to determine amyloid precursor protein (APP)-related
      cellular and biochemical changes associated with cognitive deficits. Ts65Dn mice
      showed cognitive deficits in the Morris water maze compared to LM mice at 4 and
      12 months of age. Ts65Dn, but not LM mice, developed a septohippocampal
      cholinergic neuronal degeneration of choline acetyltransferase (ChAT)-positive
      neurons at 12 months of age. These cellular changes were compensated by increases
      in ChAT enzyme activity of remaining cholinergic terminals in the hippocampus. By
      12 months of age, Ts65Dn mice had elevations of APP protein levels in the
      hippocampus compared to their LM. At this age, both Ts65Dn mice and their LM
      abnormally responded to cholinergic muscarinic M1 agonist treatment in terms of
      hippocampal APP, nerve growth factor (NGF), and brain-derived neurotrophic factor
      (BDNF) levels compared to young adult C57BL/6 mice. In summary, the Ts65Dn mice
      show developmental and progressive age-related behavioral deficits, hippocampal
      APP, and cholinergic pathology. The relatively better cognitive spatial
      performance in LM compared to Ts65Dn mice suggests that high APP levels combined
      with progressive degeneration of the cholinergic system are critical to the
      pathology and cognitive deficits seen in Ts65Dn mice.

PMID- 15869950
TI  - Glutamate induces rapid loss of axonal neurofilament proteins from cortical
      neurons in vitro.
AB  - One of the primary hallmarks of glutamate excitotoxicity is degradation of the
      neuronal cytoskeleton. Using a tissue culture approach, we have investigated the
      relationship between excitotoxicity and cytoskeletal degradation within axons,
      with particular reference to the axon specific neurofilament proteins.
      Neurofilaments were rapidly lost from axons over a 24-h period in response to
      excitotoxic insult (as observed by immunocytochemistry and western blotting),
      while other axonal cytoskeletal markers (such as betaIII-tubulin) remained
      intact. Treatment with kainic acid and NMDA, or complementary experiments using
      the pharmacological glutamate receptors blockers CNQX (kainate/AMPA receptor
      antagonist) and MK-801 (NMDA receptor antagonist), demonstrated that
      neurofilament degeneration was mediated primarily by NMDA receptor activity. This
      work suggests that excitotoxicity triggers a progressive pathway of cytoskeletal
      degeneration within axons, initially characterised by the loss of neurofilament
      proteins.

PMID- 15869951
TI  - New light on an old paradox: site-dependent effects of carbachol on circadian
      rhythms.
AB  - Acetylcholine (ACh) was the first neurotransmitter identified as a regulator of
      mammalian circadian rhythms. When injected in vivo, cholinergics induced biphasic
      clock resetting at night, similar to nocturnal light exposure. However, the
      retinohypothalamic tract connecting the eye to the suprachiasmatic nucleus (SCN)
      uses glutamate (GLU) to transmit light signals. We here resolve this long
      standing paradox. Whereas injection of the cholinergic agonist, carbachol, into
      the mouse ventricular system in vivo induced light-like effects, direct
      application to the SCN in vitro or in vivo induced a distinct response pattern:
      phase advance of circadian rhythms throughout the nighttime. These results
      indicate that a new regulatory pathway, involving an extra-SCN cholinergic
      synapse accessible via ventricular injection, mediates the light-like cholinergic
      clock resetting reported previously.

PMID- 15869952
TI  - Sulthiame but not levetiracetam exerts neurotoxic effect in the developing rat
      brain.
AB  - Antiepileptic drugs (AEDs) used to treat seizures in pregnant women, infants, and
      young children can cause cognitive impairment. One mechanism implicated in the
      development of neurocognitive deficits is a pathologic enhancement of
      physiologically occurring apoptotic neuronal death in the developing brain. We
      investigated whether the newer antiepileptic drug levetiracetam (LEV) and the
      older antiepileptic drug sulthiame (SUL) have neurotoxic properties in the
      developing rat brain. SUL significantly enhanced neuronal death in the brains of
      rat pups ages 0 to 7 days at doses of 100 mg/kg and above, whereas LEV did not
      show this neurotoxic effect. Dosages of both drugs used in the context of this
      study comply with an effective anticonvulsant dose range applied in rodent
      seizure models. Thus, LEV is an AED which lacks neurotoxicity in the developing
      rat brain and should be considered in the treatment of epilepsy in pregnant
      women, infants, and toddlers once general safety issues have been properly
      addressed.

PMID- 15869953
TI  - Direction-specific postural instability in subjects with Parkinson's disease.
AB  - The purpose of this study was to determine whether and why subjects with
      Parkinson's disease (PD) have greater instability in response to specific
      directions of perturbations than do age-matched control subjects and how
      instability is affected by stance width. This study compared postural responses
      to 8 directions of surface translations in PD subjects and age-matched control
      subjects while standing in a narrow and wide stance. PD subjects were tested in
      their practical OFF state. A postural stability margin was quantified as the
      difference between peak center of pressure (CoP) and peak center of mass (CoM)
      displacement in response to surface translations. The control subjects maintained
      a consistent stability margin across directions of translations and for both
      narrow and wide stance by modifying rate of rise of CoP responses. PD subjects
      had smaller than normal postural stability margins in all directions, but,
      especially for backwards sway in both stance widths and for lateral sway in
      narrow stance width. The reduced stability margin in PD subjects was due to a
      slower rise and smaller peak of CoP in the PD subjects than in control subjects.
      Lateral postural stability was compromised in PD subjects by lack of trunk
      flexibility and backwards postural stability was compromised by lack of knee
      flexion, resulting in excessive displacements of the body CoM. Stability margins
      in PD subjects were related to their response on the pull test in the Unified
      Parkinson's Disease Rating Scale. Thus, PD patients have directionally specific
      postural instability due to an ineffective stiffening response and inability to
      modify their postural responses for changing postural demands related to
      direction of perturbation and initial stance posture. These results suggest that
      the basal ganglia, in addition to regulating muscle tone and energizing postural
      muscle activation, also are critical for adapting postural response patterns for
      specific biomechanical conditions.

PMID- 15869954
TI  - Progesterone suppresses the inflammatory response and nitric oxide synthase-2
      expression following cerebral ischemia.
AB  - Gender differences in outcome following cerebral ischemia have frequently been
      observed and attributed to the actions of steroid hormones. Progesterone has been
      shown to possess neuroprotective properties following transient ischemia, with
      respect to decreasing lesion volume and improving functional recovery. The
      present study was designed to determine the mechanisms of progesterone
      neuroprotection, and whether these relate to the inflammatory response. Male mice
      underwent either 60 min or permanent middle cerebral artery occlusion (MCAO) and
      received progesterone (8 mg/kg ip) or vehicle 1 h, 6 h and 24 h post-MCAO. Forty
      eight hours following transient MCAO, structural magnetic resonance imaging
      revealed a significant decrease in the amount of edematous tissue present in
      progesterone-treated mice as compared with vehicle. Using real-time PCR we found
      that progesterone treatment significantly suppressed the injury-induced
      upregulation of interleukin (IL)-1beta, transforming growth factor (TGF)beta2,
      and nitric oxide synthase (NOS)-2 mRNAs in the ipsilateral hemisphere while
      having no effect on tumor necrosis factor (TNF)-alpha mRNA expression.
      Progesterone treatment following permanent MCAO also resulted in a significant
      decrease in lesion volume. This was not apparent in mice lacking a functional NOS
      2 gene. Thus, progesterone is neuroprotective in both permanent and transient
      ischemia, and this effect is related to the suppression of specific aspects of
      the inflammatory response.

PMID- 15869955
TI  - Overexpression of csc1-1. A plausible strategy to obtain wine yeast strains
      undergoing accelerated autolysis.
AB  - The potential of several alternative genetic engineering based strategies in
      order to accelerate Saccharomyces cerevisiae autolysis for wine production has
      been studied. Both constitutively autophagic and defective in autophagy strains
      have been studied. Although both alternatives lead to impaired survival under
      starvation conditions, only constitutively autophagic strains, carrying a
      multicopy plasmid with the csc1-1 allele under the control of the TDH3 promoter,
      undergo accelerated autolysis in the experimental conditions tested. Fermentation
      performance is impaired in the autolytic strains, but industrial strains carrying
      the above-mentioned construction are still able to complete second fermentation
      of a model base wine. We suggest the construction of industrial yeasts showing a
      constitutive autophagic phenotype as a way to obtain second fermentation yeast
      strains undergoing accelerated autolysis.

PMID- 15869956
TI  - Evaluation of 16S rDNA- and gyrB-DGGE for typing members of the genus Aeromonas.
AB  - The DNA sequence of the gyrB gene is a suitable phylogenetic marker for bacterial
      systematics. In this study, the diversity of Aeromonas spp. present in
      environmental samples was assessed by a PCR combined with DGGE approach. PCR
      primers targeting the gyrB gene of aeromonads were designed and the resulting
      amplicons were analyzed by DGGE. The gyrB-DGGE analysis was evaluated with
      Aeromonas isolates and reference strains allowing discrimination of the majority
      of strains. The gyrB-DGGE analysis is a powerful tool to monitor the presence and
      evaluate the diversity of aeromonads in complex samples, as is the case of water
      from a wastewater treatment plant.

PMID- 15869957
TI  - Characteristics of novel lignin peroxidases produced by white-rot fungus
      Phanerochaete sordida YK-624.
AB  - We characterized a lignin peroxidase (YK-LiP2) isolated from shaking culture
      inoculated with the white-rot fungus Phanerochaete sordida YK-624. The YK-LiP2
      enzyme was identified and purified to homogeneity by anion-exchange
      chromatography and gel permeation chromatography. The molecular weight of YK-LiP2
      was approximately 45 kDa, and its absorption spectrum was almost the same as that
      of the LiP (Pc-LiP) from P. chrysosporium. Steady-state kinetics of veratryl
      alcohol (VA) oxidation by YK-LiP2 revealed an ordered bi-bi ping-pong mechanism,
      although the Pc-LiP oxidation of ferrocytochrome c obeys peroxidase ping-pong
      kinetics rather than ordered bi-bi ping-pong kinetics. Degradation of dimeric
      lignin model compounds by YK-LiP2 was more effective than that by Pc-LiP.
      Moreover, YK-LiP2 and YK-LiP1, which was previously isolated from static culture
      inoculated with P. sordida YK-624, oxidized VA under a higher concentration of
      hydrogen peroxide (>2.5 mM) although Pc-LiP could not oxidize VA in the presence
      of 2.5 mM hydrogen peroxide.

PMID- 15869958
TI  - Malate:quinone oxidoreductase (MqoB) is required for growth on acetate and linear
      terpenes in Pseudomonas citronellolis.
AB  - Mini-transposon-induced mutants with defects in utilization of linear terpenes
      such as citronellol and citronellic acid were isolated from Pseudomonas
      citronellolis. Mutants with strongly reduced growth on citronellol and
      citronellic acid (class I) were obtained together with mutants growing normally
      on citronellic acid but with impairment in growth on citronellol (class II) and
      auxotroph mutants (class III). The transposon carrying DNA fragments of two class
      I mutants were cloned and malate:quinone oxidoreductase gene (mqoB) was
      identified as the transposon insertion site in both mutants. The mqoB genes of P.
      aeruginosa and of P. citronellolis wild types were cloned. Conjugative transfer
      of the mqoB genes to the two P. citronellolis mutants increased the strongly
      reduced levels of MqoB activity in cell extracts of the mutants to the level of
      the wild type and restored the ability of the mutants to grow on citronellol and
      citronellic acid. Physiological analysis of the wild type and of mutants showed
      that MqoB is part of the glyoxylate cycle in P. citronellolis and is necessary
      for growth on C(2)-compounds and linear terpenes such as citronellol or
      citronellic acid.

PMID- 15869959
TI  - Contamination of diverse nifH and nifH-like DNA into commercial PCR primers.
AB  - False-positive results due to DNA contamination in PCR reagents have become a big
      problem in the amplification of small amounts of DNA. Recently, it was revealed
      that PCR reagents were contaminated with the nifH (dinitrogenase reductase) gene.
      We found that the PCR primers supplied by some manufacturers contained nifH gene
      and nifH-like DNA. This contamination resulted in false-positive results when
      searching for nifH genes in environmental samples. The sequences of the
      contaminating DNA appeared to be widely varied in the phylogenetic analysis of
      nifH. For this reason, great care should be taken when analyzing trace amounts of
      nucleotides.

PMID- 15869960
TI  - Efficacy of species-specific recA PCR tests in the identification of Burkholderia
      cepacia complex environmental isolates.
AB  - In this study, we evaluated if recA species-specific PCR assays could be
      successfully applied to identify environmental isolates of the widespread
      Burkholderia cepacia complex (Bcc) species. A total of 729 Bcc rhizosphere
      isolates collected in different samplings were assigned to the species B. cepacia
      genomovar I (61), B. cenocepacia recA lineage IIIB (514), B. ambifaria (124) and
      B. pyrrocinia (30), by means of recA (RFLP) analysis, and PCR tests were
      performed to assess sensitivity and specificity of recA species-specific primers
      pairs. B. cepacia genomovar I specific primers produced the expected amplicon
      with all isolates of the corresponding species (sensitivity, 100%), and cross
      reacted with all B. pyrrocinia isolates. On the contrary, B. cenocepacia IIIB
      primers did not give the expected amplicon in 164 B. cenocepacia IIIB isolates
      (sensitivity, 68.1%), and isolates of distinct populations showed different
      sensitivity. B. ambifaria primers failed to amplify a recA-specific fragment only
      in a few isolates of this species (sensitivity, 93.5%). The absence of specific
      amplification in a high number of B. cenocepacia rhizosphere isolates indicates
      that recA specific PCR assays can lead to an underestimation of environmental
      microorganisms belonging to this bacterial species.

PMID- 15869961
TI  - Insights into the oxidative stress response in Francisella tularensis LVS and its
      mutant DeltaiglC1+2 by proteomics analysis.
AB  - Francisella tularensis is a facultative intracellular pathogen. Its capacity to
      induce disease depends on the ability to invade and multiply within a wide range
      of eukaryotic cells, such as professional phagocytes. The comparative disinterest
      in tularemia in the past relative to other human bacterial pathogens is reflected
      in the paucity of information concerning the mechanisms of pathogenesis. Only a
      few genes and gene products associated with Francisella virulence are known to
      date. The aim of this study was to find and identify proteins of F. tularensis
      live vaccine strain induced in the presence of hydrogen peroxide, and to
      investigate the role of the IglC protein in the regulation of genes expressed
      upon peroxide stress. The [(35)S]-radiolabelled protein patterns were examined
      for both the wild live vaccine strain and its DeltaiglC1+2 mutant defective in
      synthesis of the IglC protein that was found to be strongly up-regulated during
      intracellular growth in murine macrophages in vitro and upon exposure to hydrogen
      peroxide. Globally, we found 21 protein spots whose levels were significantly
      altered in the presence of hydrogen peroxide in both the wild-type and mutant
      strains.

PMID- 15869962
TI  - Characterization of Shiga toxin-producing Escherichia coli isolated from aquatic
      environments.
AB  - This study reports the phenotypic and genotypic characterization of 144 Shiga
      toxin-producing Escherichia coli (STEC) strains isolated from urban sewage and
      animal wastewaters using a Shiga toxin 2 gene variant (stx(2))-specific DNA
      colony hybridization method. All the strains were classified as E. coli and
      belonged to 34 different serotypes, some of which had not been previously
      reported to carry the stx(2) genes (O8:H31, O89:H19, O166:H21 and O181:H20). Five
      stx(2) subtypes (stx(2), stx(2c), stx(2d), stx(2e) and stx(2g)) were detected.
      The stx(2), stx(2c), stx(2d) and stx(2e) subtypes were present in urban sewage
      and stx(2e) was the only stx(2) subtype found in pig wastewater samples. The
      stx(2c) and stx(2g) were more associated with cattle wastewater. One strain was
      positive for the intimin gene (eae) and five strains of serotypes were positive
      for the adhesin encoded by the saa gene. A total of 41 different seropathotypes
      were found. On the basis of occurrence of virulence genes, most non-O157 STEC
      strains are assumed to be low-virulence serotypes.

PMID- 15869963
TI  - Secretory production of biologically active rat interleukin-2 by Clostridium
      acetobutylicum DSM792 as a tool for anti-tumor treatment.
AB  - The search for effective means of selectively delivering high therapeutic doses
      of anti-cancer agents to tumors has explored a variety of systems in the last
      decade. The ability of intravenously injected clostridial spores to infiltrate
      and thence selectively germinate in the hypoxic regions of solid tumors is
      exquisitely specific, making this system an interesting addition to the anti
      cancer therapy arsenal. To increase the number of therapeutic proteins
      potentially useful for cancer treatment we have tested the possibility of
      Clostridium acetobutylicum to secrete rat interleukin-2 (rIL2). Therefore, rIL2
      cDNA was placed under the control of the endo-beta-1,4-glucanase promoter and
      signal sequence of C. saccharobutylicum. Recombinant C. acetobutylicum containing
      the relevant construct secreted up to 800 microgl(-1) biologically active rIL2.
      The obtained yield should be sufficient to provoke in vivo effects.

PMID- 15869964
TI  - Complex pattern formation of marine gradient bacteria explained by a simple
      computer model.
AB  - We report on the formation of conspicuous patterns by the sulfide-oxidizing
      bacterium Thiovulum majus and a recently described vibrioid bacterium. These
      microaerophilic bacteria form mucus veils on top of sulfidic marine sediment
      exhibiting regular spaced bacterial patterns (honeycombs, interwoven bands, or
      inverse honeycombs). A simple qualitative computer model, based on chemotaxis
      towards oxygen and the ability of the bacteria to induce water advection when
      attached, can explain the formation of the observed patterns. Our study shows
      that complex bacterial patterns in nature can be explained in terms of chemotaxis
      and resource optimisation without involvement of cell-cell signalling or social
      behavior amongst bacteria.

PMID- 15869965
TI  - Prevalence of cna, fnbA and fnbB adhesin genes among Staphylococcus aureus
      isolates from orthopedic infections associated to different types of implant.
AB  - Here are reported data on virulence determinants of Staphylococcus aureus from
      orthopedic surgical infections, emphasizing on the genes encoding fibronectin
      (fnbA, fnbB) and collagen (cna) adhesins. 191 S. aureus strains from orthopedic
      infections (53 from internal fixation devices, 29 external fixation devices, 15
      knee arthroprostheses, 30 hip arthroprostheses, 45 surgical reconstruction and 19
      non-associated to medical devices) were investigated for the presence of the
      genes of the collagen-binding protein Cna and of the two fibronectin-binding
      proteins, FnbA and FnbB. 87 (46%) strains were found to be cna+ without
      significant variations across the different surgical categories considered.
      Conversely, the fnbA and the fnbB genes were almost always present in all
      surgical categories. The finding that, among the investigated adhesins,
      fibronectin-adhesins are present in the majority of the implant associated S.
      aureus clinical isolates encourages the development of strategies to specifically
      block the interaction of bacteria with matrix fibronectin by antagonist ligands.

PMID- 15869966
TI  - Identification of a novel domain--DIM, which defines a new family composed mainly
      of bacterial membrane proteins.
AB  - We report here the identification of a novel domain - DIM (N-terminal domain in
      bacterial membrane proteins and other proteins) present exclusively in bacterial
      species including mycobacteria, revealed by PSI-BLAST iterative searches. DIM
      comprises about 53 amino acids in length with conserved Leu, Ile and Gly
      residues. Secondary structure prediction indicated that this domain contains two
      alpha-helices. DIM occurs at the N-terminus of proteins, and was found
      particularly but not exclusively in proteins with a transmembrane domain, and
      also in proteins with a FHA domain or RPT repeats. DIM-containing proteins have
      been reported to be involved in pathogenicity, signal transduction or small
      solute transport.

PMID- 15869967
TI  - Marker-free chromosomal integration of the manganese superoxide dismutase gene
      (sodA) from Streptococcus thermophilus into Lactobacillus gasseri.
AB  - A strategy for functional gene replacement in the chromosome of Lactobacillus
      gasseri is described. The phospho-beta-galactosidase II gene (lacII) was
      functionally replaced by the manganese superoxide dismutase (MnSOD) gene (sodA)
      from Streptococcus thermophilus, by adapting the insertional inactivation method
      described for lactobacilli [Russell, W.M. and Klaenhammer, T.R. 2001 Efficient
      system for directed integration into the Lactobacillus acidophilus and
      Lactobacillus gasseri chromosomes via homologous recombination. Appl. Environ.
      Microbiol. 67, 4361-4364]. L. gasseri carrying the heterologous sodA gene grew on
      lactose as efficiently as the wild-type parent. An active MnSOD was expressed in
      the transgenic strain, and the enzyme migrated on PAGE-SOD activity gels to the
      same position as that of MnSOD from S. thermophilus. The expression of MnSOD from
      a single copy of sodA integrated in the chromosome of L. gasseri provided
      enhanced tolerance to hydrogen peroxide, and extended the viability of
      carbon/energy starved cultures stored at 25 degrees C. This is the first report
      showing the successful utilization of the pORI plasmids system to generate marker
      free gene integration in L. gasseri strains.

PMID- 15869968
TI  - C-terminus mutations of Acremonium chrysogenum deacetoxy/deacetylcephalosporin C
      synthase with improved activity toward penicillin analogs.
AB  - Deacetoxy/deacetylcephalosporin C synthase (acDAOC/DACS) from Acremonium
      chrysogenum is a bifunctional enzyme that catalyzes both the ring-expansion of
      penicillin N to deacetoxycephalosporin C (DAOC) and the hydroxylation of the
      latter to deacetylcephalosporin C (DAC). Three residues N305, R307 and R308
      located in close proximity to the C-terminus of acDAOC/DACS were each mutated to
      leucine. The N305L and R308L mutant acDAOC/DACSs showed significant improvement
      in their ability to convert penicillin analogs. R308 was identified for the first
      time as a critical residue for DAOC/DACS activity. Kinetic analyses of purified
      R308L enzyme indicated its improved catalytic efficiency is due to combined
      improvements of K(m) and k(cat). Comparative modeling of acDAOC/DACS supports the
      involvement of R308 in the formation of substrate-binding pocket.

PMID- 15869969
TI  - Population dynamics of Oenococcus oeni strains in a new winery and the effect of
      SO2 and yeast strain.
AB  - The effects of different yeast starters and SO(2) addition on malolactic
      fermentation in a new winery were evaluated by a molecular approach in three
      vintages. Alcoholic fermentations with 40 and 100mgl(-1) SO(2) were carried out,
      followed by uninoculated malolactic fermentations. Isolated colonies of
      Oenococcus oeni obtained from samples throughout the vinification were identified
      and typified by multiplex RAPD-PCR. This made it possible to monitor the
      population dynamics and follow the proportion of as many as 29 different
      indigenous strains. In one of the vintages, O. oeni strains were more inhibited
      when a specific yeast starter was used.

PMID- 15869971
TI  - Growth and indole-3-acetic acid biosynthesis of Azospirillum brasilense Sp245 is
      environmentally controlled.
AB  - Batch and fed batch cultures of Azospirillum brasilense Sp245 were conducted in a
      bioreactor. Growth response, IAA biosynthesis and the expression of the ipdC gene
      were monitored in relation to the environmental conditions (temperature,
      availability of a carbon source and aeration). A. brasilense can grow and produce
      IAA in batch cultures between 20 and 38 degrees C in a standard minimal medium
      (MMAB) containing 2.5 gl(-1)l-malate and 50 microgml(-1) tryptophan. IAA
      synthesis requires depletion of the carbon source from the growth medium in batch
      culture, causing growth arrest. No significant amount of IAA can be detected in a
      fed batch culture. Varying the concentration of tryptophan in batch experiments
      has an effect on both growth and IAA synthesis. Finally we confirmed that aerobic
      growth inhibits IAA synthesis. The obtained profile for IAA synthesis coincides
      with the expression of the indole-3-pyruvate decarboxylase gene (ipdC), encoding
      a key enzyme in the IAA biosynthesis of A. brasilense.

PMID- 15869970
TI  - Co-cultivation of antifungal Lactobacillus plantarum MiLAB 393 and Aspergillus
      nidulans, evaluation of effects on fungal growth and protein expression.
AB  - The fungal inhibitory effects of strain Lactobacillus plantarum MiLAB 393,
      producing broad-spectrum antifungal compounds, were evaluated. A co-cultivation
      method was set up to monitor effects on fungal growth and protein expression of
      growing Aspergillus nidulans with L. plantarum MiLAB 393. The effects of
      inhibitory metabolites produced by L. plantarum MiLAB 393, cyclo(l-Phe-l-Pro),
      lactic acid and 3-phenyllactic acid, were also investigated by addition of pure
      compounds to the growth medium of A. nidulans. The co-cultivation strongly
      affected the morphology of the fungal mycelium and decreased the biomass to 36%
      of control. Co-cultivation with Lactobacillus coryniformis MiLAB 123 gave only
      marginal morphological changes and minor biomass reduction, suggesting specific
      effects of L. plantarum MiLAB 393. The amount of several A. nidulans-proteins was
      increased during co-cultivation and by all of the inhibiting substances. This
      study shows that the growth of A. nidulans is inhibited during co-cultivation
      with L. plantarum MiLAB 393 and that the expression of fungal proteins is
      altered.

PMID- 15869972
TI  - Oligonucleotide microarray for identification of Enterococcus species.
AB  - For detection of most members of the Enterococcaceae, the specificity of a novel
      oligonucleotide microarray (ECC-PhyloChip) consisting of 41 hierarchically nested
      16S or 23S rRNA gene-targeted probes was evaluated with 23 pure cultures
      (including 19 Enterococcus species). Target nucleic acids were prepared by PCR
      amplification of a 4.5-kb DNA fragment containing large parts of the 16S and 23S
      rRNA genes and were subsequently labeled fluorescently by random priming. Each
      tested member of the Enterococcaceae was correctly identified on the basis of its
      unique microarray hybridization pattern. The evaluated ECC-PhyloChip was
      successfully applied for identification of Enterococcus faecium and Enterococcus
      faecalis in artificially contaminated milk samples demonstrating the utility of
      the ECC-PhyloChip for parallel identification and differentiation of Enterococcus
      species in food samples.

PMID- 15869974
TI  - 1st UK conference and exhibition on biodegradable and residual waste management.

PMID- 15869973
TI  - Microbial community dynamics in bioaugmented sequencing batch reactors for
      bromoamine acid removal.
AB  - Sphingomonas xenophaga QYY with the ability to degrade bromoamine acid (BAA) was
      previously isolated from sludge samples. The enhancement of BAA removal by strain
      QYY in sequencing batch reactors (SBRs) was investigated in this study. The
      results showed that augmented SBRs exhibited stronger abilities to degrade BAA
      than the non-augmented control one. In order to estimate the relationship between
      community dynamics and function of augmented SBRs, a combined method based on
      fingerprints (ribosomal intergenic spacer analysis, RISA) and 16S rRNA gene
      sequencing was used. The results indicated that the microbial community dynamics
      were substantially changed, and the introduced strain QYY was persistent in the
      augmented systems. This study suggests that it is feasible and potentially useful
      to enhance BAA removal using BAA-degrading bacteria, such as S. xenophaga QYY.

PMID- 15869975
TI  - Influence of mechanical-biological waste pre-treatment methods on the gas
      formation in landfills.
AB  - In order to minimise emissions and environmental impacts, only pre-treated waste
      should be disposed of. For the last six years, a series of continuous experiments
      has been conducted at the Institute WAR, TU Darmstadt, in order to determine the
      emissions from pre-treated waste. Different kinds of pre-treated waste were
      incubated in several reactors and various data, including production and
      composition of the gas and the leachate, were collected. In this paper, the
      interim results of gas production and the gas composition from different types of
      waste after a running time of six years are presented and discussed.

PMID- 15869976
TI  - CH4 and N2O from mechanically turned windrow and vermicomposting systems
      following in-vessel pre-treatment.
AB  - Methane (CH4) and nitrous oxide (N2O) are included in the six greenhouse gases
      listed in the Kyoto protocol that require emission reduction. To meet reduced
      emission targets, governments need to first quantify their contribution to global
      warming. Composting has been identified as an important source of CH4 and N2O.
      With increasing divergence of biodegradable waste from landfill into the
      composting sector, it is important to quantify emissions of CH4 and N2O from all
      forms of composting and from all stages. This study focuses on the final phase of
      a two stage composting process and compares the generation and emission of CH4
      and N2O associated with two differing composting methods: mechanically turned
      windrow and vermicomposting. The first stage was in-vessel pre-treatment. Source
      segregated household waste was first pre-composted for seven days using an in
      vessel system. The second stage of composting involved forming half of the pre
      composted material into a windrow and applying half to vermicomposting beds. The
      duration of this stage was 85 days and CH4 and N2O emissions were monitored
      throughout for both systems. Waste samples were regularly subjected to
      respirometry analysis and both processes were found to be equally effective at
      stabilising the organic matter content. The mechanically turned windrow system
      was characterised by emissions of CH4 and to a much lesser extent N2O. However,
      the vermicomposting system emitted significant fluxes of N2O and only trace
      amounts of CH4. In-vessel pre-treatment removed considerable amounts of available
      C and N prior to the second stage of composting. This had the effect of reducing
      emissions of CH4 and N2O from the second stage compared to emissions from fresh
      waste found in other studies. The characteristics of each of the two composting
      processes are discussed in detail. Very different mechanisms for emission of CH4
      and N2O are proposed for each system. For the windrow system, development of
      anaerobic zones were thought to be responsible for CH4 release. High N2O emission
      rates from vermicomposting were ascribed to strongly nitrifying conditions in the
      processing beds combined with the presence of de-nitrifying bacteria within the
      worm gut.

PMID- 15869977
TI  - Pollutant release and pollutant reduction--impact of the aeration of landfills.
AB  - The in situ stabilization of old deposits aims for a lasting and controlled
      reduction of pollutant emissions from the deposited waste in order to diminish
      expenditure and the duration of landfill aftercare measures. The stabilization
      operation so far, observed over a period of 1-2 years at three landfills in
      Germany, shows that leachate contamination is permanently reduced, biodegradation
      processes are significantly accelerated and main settlements take place within a
      short period of time.

PMID- 15869978
TI  - Modelling of nitrogen release from MBT waste.
AB  - The "LaNDy" model (landfill nitrogen dynamics model) is a new mathematical tool
      for the evaluation of the long-term behaviour of nitrogen in mechanical
      biologically pretreated (MBP) waste. LaNDy combines a hydraulic model based on
      RICHARD's equation with one-dimensional heat flow in landfills, kinetics of
      biological degradation, gas diffusion, nitrification and denitrification. A
      suitable temperature-dependent N mineralisation sub-model was based on numerous
      data from the literature and own LSR-experiments. With the "nitrification modus"
      of the LaNDy model, kinetic data of nitrification, thermodynamic data of
      denitrification and diffusion characteristics of gaseous components (especially
      of oxygen and methane) are used as an additional input for the preliminary
      calculation of the long-time impact of nitrification and denitrification.
      Examples of predicted temperature distribution and leachate ammonium
      concentrations, using different landfill size, age of the landfill (10 to
      approximately 100 a) and hydraulic conductivity of the MBP waste, are presented
      in this paper.

PMID- 15869979
TI  - Methane oxidation in a landfill cover with capillary barrier.
AB  - The methane oxidation potential of a landfill cover with capillary barrier was
      investigated in an experimental plant (4.8 m x 0.8 m x 2.1m). The cover soil
      consisted of two layers, a mixture of compost plus sand (0.3 m) over a layer of
      loamy sand (0.9 m). Four different climatic conditions (summer, winter, spring
      and fall) were simulated. In and outgoing fluxes were measured. Gas composition,
      temperature, humidity, matrix potential and gas pressure were monitored in two
      profiles. CH4 oxidation rate within the investigated top cover ranged from 98% to
      57%. The minimum was observed for a short time after irrigation. Temperature
      distribution, gas concentration profiles and lab-scaled batch experiments
      indicate that before irrigation the highest oxidising activity took place in a
      depth of about 30 cm. After irrigation the oxidising horizon seemed to migrate
      upwards since methanotrophic bacteria develop better there due to an adequate
      supply with oxygen. It can be assumed that the absence of oxygen is one of the
      most important limiting factors for the CH4 oxidation process. Abrupt cross-overs
      between horizons of different soil material may lead to zones of increased water
      saturation and decreased soil respiration.

PMID- 15869980
TI  - Increase of the purification efficiency of biofilters by the use of a
      complementary ionisation step.
AB  - The biofilter and the ionisation system are two oxidative treatment techniques
      for purification of waste gas streams with low concentrations of volatile organic
      compounds. In this paper, the authors present the investigations of an ionisation
      technique aimed at increasing the efficiency of the reduction of the odorant
      concentration in waste gas streams from biological waste treatment plants. The
      objective is to enable advanced odour emission reduction and to adjust the
      existing biofilters to stricter requirements. In a first step, the odorous
      substances which are major contributors to the overall odorant concentration are
      identified on basis of various emission data sets with the help of a method of
      life cycle impact assessment. Thereby limonene, alpha-pinene, ethyl butyrate and
      dimethyl disulphide were identified as crucial indicators. In a second step,
      experimental investigations using limonene as a model compound were conducted to
      gain an understanding of the ionisation process itself and at last for the
      evaluation of the system.

PMID- 15869981
TI  - Leachate quality from landfilled MBT waste.
AB  - A research project recently completed on behalf of the UK Environment Agency, has
      collected data and sampled leachates from EU landfills that have received imports
      of MSOR and MBT wastes. Results are presented for sanitary analyses, heavy
      metals, and an extensive range of trace organic substances, from sites containing
      MBT wastes that have received different degrees of composting pre-treatment.
      Leachates produced from MSOR wastes have a very high polluting potential, but
      biological pre-treatment of these wastes can avoid the peak acetogenic phase of
      decomposition, and produce leachates similar to, or weaker than, those from
      conventional methanogenic landfills. Effective MBT processes can also
      significantly reduce concentrations of trace organics, and of ammoniacal-N in
      leachates. However, further research is needed to examine the relative importance
      of nitrification/denitrification processes, generation of stable, organically
      based nitrogen forms, and other routes during MBT processing, in order that
      appropriate reactions to remove nitrogen can be encouraged and optimised.

PMID- 15869982
TI  - Feasibility study for co-digestion of sewage sludge with OFMSW on two wastewater
      treatment plants in Germany.
AB  - In the past years, wastewater treatment plants (WWTP) in Germany have often been
      enlarged or expanded. However, it has become evident that the prognosticated
      increase in wastewater amount has not become a reality and thus free capacities,
      particularly in the sewage sludge digesters, are available. A possibility for the
      use of these available capacities is the fermentation of sewage sludge together
      with organic waste. A feasibility study for two different wastewater treatment
      plants in Germany was done in order to estimate if fermentation of the organic
      fraction of municipal solid waste (OFMSW) affects the wastewater treatment plant
      operation. In this study, the technical, economic and ecological aspects of co
      digestion were investigated for the plants selected.

PMID- 15869983
TI  - Open windrow composting of polymers: an investigation into the operational issues
      of composting polyethylene (PE).
AB  - This paper investigates the operational issues surrounding the open windrow
      composting of degradable polyethylene sacks. Areas for consideration were the
      impact of degradable polyethylene sacks on the composting process, the quality of
      the finished compost product, and how the use of sacks influenced the on-site
      processing. These factors were investigated through determining the amount of
      polymer residue and chemical contaminants in the finished compost product and the
      daily monitoring of windrow temperature profiles. Site and practical handling
      considerations of accepting an organic waste contained within PE sacks are also
      discussed. Statistical analysis of the windrow temperature profiles has led to
      the development of a model that can help to predict the expected trends in the
      temperature profiles of open compost windrows where the organic waste is kerbside
      collected using a degradable PE sack.

PMID- 15869984
TI  - Behaviour of biodegradable plastics in composting facilities.
AB  - Composting is a preferred treatment strategy for biodegradable plastics (BDPs).
      In this sense, the collection of BDPs together with organic household wastes is a
      highly discussed possibility. Under the aspect of the behaviour of BDPs in
      composting facilities, a telephone survey was carried out with selected
      composting facility operators. They were interviewed with respect to treated
      wastes, content of impurities, processes for impurity separation, experiences
      with biodegradable plastics and assumptions to the behaviour of biodegradable
      plastics in their facility. Forty percent of the facilities had some experiences
      with BDPs due to test runs, and also since the occurrence of BDPs in their waste
      was known. The majority of the operators expressed apprehension regarding an
      increase of impurities resulting from a combined collection of biowaste and BDPs.
      In the facilities, measures for the impurity separation from the biowaste were
      used in common practice - in 33% of the cases, separation of disturbing plastics
      was done before composting, in 33% after composting, and in 13% before and after
      composting. The most important separation processes for conventional plastics
      were sieving and manual sorting. In two cases air classification was also used.
      When asked about the separation possibility of the conventional but not of the
      biodegradable plastics in their facilities, the majority of operators were not in
      a position to comment or they replied that it was not an option. No problems were
      seen in most cases if the impurity separation follows composting. If impurity
      separation takes place before composting it was often assumed that the BDPs are
      mainly separated by sieving. In conclusion, in more than half of the cases, BDPs
      would not be composted if delivered to a composting facility. Under the actual
      conditions regarding the collection and the treatment/disposal possibilities, an
      application of BDPs seems to only be reasonable for clean (i.e., source separated
      on their own) fractions of BDPs.

PMID- 15869985
TI  - Factors controlling pathogen destruction during anaerobic digestion of biowastes.
AB  - Anaerobic digestion is the principal method of stabilising biosolids from urban
      wastewater treatment in the UK, and it also has application for the treatment of
      other types of biowaste. Increasing awareness of the potential risks to human and
      animal health from environmental sources of pathogens has focused attention on
      the efficacy of waste treatment processes at destroying pathogenic microorganisms
      in biowastes recycled to agricultural land. The degree of disinfection achieved
      by a particular anaerobic digester is influenced by a variety of interacting
      operational variables and conditions, which can often deviate from the ideal.
      Experimental investigations demonstrate that Escherichia coli and Salmonella spp.
      are not damaged by mesophilic temperatures, whereas rapid inactivation occurs by
      thermophilic digestion. A hydraulic, biokinetic and thermodynamic model of
      pathogen inactivation during anaerobic digestion showed that a 2 log10 reduction
      in E. coli (the minimum removal required for agricultural use of conventionally
      treated biosolids) is likely to challenge most conventional mesophilic digesters,
      unless strict maintenance and management practices are adopted to minimise dead
      zones and by-pass flow. Efficient mixing and organic matter stabilisation are the
      main factors controlling the rate of inactivation under mesophilic conditions and
      not a direct effect of temperature per se on pathogenic organisms.

PMID- 15869986
TI  - Occupational hygiene in a Finnish drum composting plant.
AB  - Bioaerosols (microbes, dust and endotoxins) and volatile organic compounds (VOCs)
      were determined in the working air of a drum composting plant treating source
      separated catering waste. Different composting activities at the Oulu drum
      composting plant take place in their own units separated by modular design and
      constructions. Important implication of this is that the control room is a
      relatively clean working environment and the risk of exposure to harmful factors
      is low. However, the number of viable airborne microbes was high both in the
      biowaste receiving hall and in the drum composting hall. The concentration
      (geometric average) of total microbes was 21.8 million pcs/m3 in the biowaste
      receiving hall, 13.9 million pcs/m3 in the drum composting hall, and just 1.4
      million pcs/m3 in the control room. Endotoxin concentrations were high in the
      biowaste receiving hall and in the drum composting hall. The average (arithmetic)
      endotoxin concentration was over the threshold value of 200 EU/m3 in both
      measurement locations. In all working areas, the average (arithmetic) dust
      concentrations were in a low range of 0.6-0.7 mg/m3, being below the Finnish
      threshold value of 5 mg/m3. In the receiving hall and drum composting hall, the
      concentrations of airborne microbes and endotoxins may rise to levels hazardous
      to health during prolonged exposure. It is advisable to use a respirator mask
      (class P3) in these areas. Detected volatile organic compounds were typical
      compounds of composting plants: carboxylic acids and their esters, alcohols,
      ketones, aldehydes, and terpenes. Concentrations of VOCs were much lower than the
      Finnish threshold limit values (Finnish TLVs), many of the quantified compounds
      exceeded their threshold odour concentrations (TOCs). Primary health effects due
      VOCs were not presumable at these concentrations but unpleasant odours may cause
      secondary symptoms such as nausea and hypersensitivity reactions. This situation
      is typical of composting plants where the workers are exposed to dozens of VOCs
      simultaneously. The odour units (OU/m3) were measured using olfactometer. The
      numbers were 23,000 OU/m3 at the output end of the composting drum and 6300 OU/m3
      in the exhaust pipe. Inside the composting hall, the number of odour units was
      500 and 560 OU/m3.

PMID- 15869987
TI  - Indicator methods to evaluate the hygienic performance of industrial scale
      operating Biowaste Composting Plants.
AB  - The hygienic performance of biowaste composting plants to ensure the quality of
      compost is of high importance. Existing compost quality assurance systems reflect
      this importance through intensive testing of hygienic parameters. In many
      countries, compost quality assurance systems are under construction and it is
      necessary to check and to optimize the methods to state the hygienic performance
      of composting plants. A set of indicator methods to evaluate the hygienic
      performance of normal operating biowaste composting plants was developed. The
      indicator methods were developed by investigating temperature measurements from
      indirect process tests from 23 composting plants belonging to 11 design types of
      the Hygiene Design Type Testing System of the German Compost Quality Association
      (BGK e.V.). The presented indicator methods are the grade of hygienization, the
      basic curve shape, and the hygienic risk area. The temperature courses of single
      plants are not distributed normally, but they were grouped by cluster analysis in
      normal distributed subgroups. That was a precondition to develop the mentioned
      indicator methods. For each plant the grade of hygienization was calculated
      through transformation into the standard normal distribution. It shows the part
      in percent of the entire data set which meet the legal temperature requirements.
      The hygienization grade differs widely within the design types and falls below
      50% for about one fourth of the plants. The subgroups are divided visually into
      basic curve shapes which stand for different process courses. For each plant the
      composition of the entire data set out of the various basic curve shapes can be
      used as an indicator for the basic process conditions. Some basic curve shapes
      indicate abnormal process courses which can be emended through process
      optimization. A hygienic risk area concept using the 90% range of variation of
      the normal temperature courses was introduced. Comparing the design type range of
      variation with the legal temperature defaults showed hygienic risk areas over the
      temperature courses which could be minimized through process optimization. The
      hygienic risk area of four design types shows a suboptimal hygienic performance.

PMID- 15869988
TI  - Estimating fugitive bioaerosol releases from static compost windrows: feasibility
      of a portable wind tunnel approach.
AB  - An assessment of the fugitive release of bioaerosols from static compost piles
      was conducted at a green waste composting facility in South East England; this
      representing the initial stage of a programme of research into the influence of
      process parameters on bioaerosol emission flux. Wind tunnel experiments conducted
      on the surface of static windrows generated specific bioaerosol emission rates
      (SBER2s) at ground level of between 13 and 22 x 10(3) cfu/m2/s for mesophilic
      actinomycetes and between 8 and 11 x 10(3)cfu/m2/s for Aspergillus fumigatus. Air
      dispersion modelling of these emissions using the SCREEN3 air dispersion model in
      area source term mode was used to generate source depletion curves downwind of
      the facility for comparative purposes.

PMID- 15869989
TI  - Why energy from waste incineration is an essential component of environmentally
      responsible waste management.
AB  - This paper outlines the key factors involved in adopting energy from waste
      incineration (EfWI) as part of a waste management strategy. Incineration means
      all forms of controlled direct combustion of waste. 'Emerging' technologies, such
      as gasification, are, in the author's view, 5 to 10 years from proven commercial
      application. The strict combustion regimen employed and the emissions therefrom
      are detailed. It is shown that EfWI merits consideration as an integral part of
      an environmentally responsible and sustainable waste management strategy, where
      suitable quantities of waste are available.

PMID- 15869990
TI  - The effects of stage divergence on survival after radical cystectomy for
      urothelial cancer.
AB  - INTRODUCTION: Discrepancies between clinical and pathologic staging, herein
      referred to as stage divergence, are common after radical cystectomy. The
      implications of stage divergence on survival are ill defined in the context of
      those treated by surgery alone and would facilitate patient counseling and
      enhance prognostication. METHODS: There were 78 consecutive radical cystectomy
      patients with clinical stage T2 or less urothelial carcinoma who comprised our
      study population. Kaplan-Meier plots were constructed to determine the effects of
      stage divergence on survival and the log-rank test employed to assess the
      significance. Regression models were developed to determine predictors of overall
      and cancer-specific survival. RESULTS: Stage divergence was common after radical
      cystectomy with downstaging and upstaging occurring in 27% and 49% of patients,
      respectively. Downstaged patients had better overall (P = 0.003) and bladder
      cancer-specific (P = 0.0004) survivals. None of the downstaged patient died from
      bladder cancer (median follow-up 35.9 months). Upstaged patients were five times
      as likely to succumb from bladder cancer or other illness compared to downstaged
      patients. This effect was not isolated to patients with lower clinical stages but
      also demonstrated in patients with clinical stage T2 bladder cancer. CONCLUSIONS:
      Stage divergence is common after radical cystectomy occurring in 76% of patients
      in this study. The implications of stage divergence are equally relevant for
      those who are upstaged or downstaged in terms of survival, and such data is
      useful when counseling patients postoperatively. Downstaging at the time of
      radical cystectomy is associated with better overall and cancer-specific
      survival.

PMID- 15869991
TI  - Phase II trial of GM-CSF + thalidomide in patients with androgen-independent
      metastatic prostate cancer.
AB  - BACKGROUND: Androgen-independent metastatic prostate cancer is a major
      therapeutic dilemma. Granulocyte-macrophage colony stimulating factor (GM-CSF)
      and thalidomide have some biologic activity as single agents in this disease
      subset. We performed a Phase II trial of this combination to assess its toxicity
      and potential utility as an immunomodulatory approach to management of advanced
      prostate cancer. METHODS: Twenty-two patients were treated with GM-CSF 250 microg
      administered SC on Monday, Wednesday and Friday of each week. Thalidomide was
      escalated to reach the study dose of 200 mg/day. Patients were assessed every 4
      weeks with therapy continuing to a maximum of 6 months. RESULTS: All 22 patients
      had a decrement in PSA at 2 weeks postinitiation of therapy. Five patients had a
      > or =50% decline (56, 64,66,66, and 94%, respectively) from baseline verified at
      4 weeks post best response. This corresponds to an observed response rate of 23%
      (95% confidence interval 8-45%). Therapy was well tolerated with the majority of
      patients experiencing only one event. CONCLUSIONS: The combination of GM-CSF +
      thalidomide is relatively well tolerated and has the potential to produce
      antitumor activity in a population of patients with metastatic, androgen
      independent prostate cancer. This nonchemotherapy combination should be explored
      in a subset of patients with less advanced disease.

PMID- 15869992
TI  - High frequency of allelic losses in high-grade prostate cancer is associated with
      biochemical progression after radical prostatectomy.
AB  - Loss of heterozygosity (LOH) is the most consistent genetic change in prostate
      cancer (CaP). We aimed, to correlate specific LOH and the overall LOH frequency,
      to disease progression after radical prostatectomy (RP) in high-grade CaP.
      Between January 1990 through December 1998, 126 patients who underwent RP (cT1
      T2), Gleason 8-10, were pT3, or pN1, or SM(+) (surgical margins). Nine were lost
      of follow-up, 39/117 (33%) had no biochemical progression (mean follow-up: 45
      months). After exclusion for preoperative PSA >50 ng/mL, a case-control study was
      designed by matching 26 of these cases with 26 similar patients without
      biochemical progression (criteria: pT, pN, year of surgery). Using microsatellite
      markers, LOH were assessed on six chromosomal regions (7q31, 8p22, 12p13, 13q14,
      16q23.2, 18q21). No prognostic value was associated with LOH at any one specific
      locus. However, the overall LOH frequency (five classes, cutoff of 60%), was
      significantly higher if progression (P = 0.02; P = 0.03) in SM(+) patients, and
      was near statistical significance (P = 0.08; P = 0.07) for the overall case
      control population. In multivariate analysis (overall population), the overall
      LOH rate > or =60% was independently associated with progression [P = 0.035; Odds
      Ratio (OR) = 5.54]. An overall LOH rate > or =60% predicted poor outcome in 85%
      of SM(+) patients and 69% of the whole population. Our results suggest that the
      overall rate of LOH at chromosomal "hot spots" is more likely to be predictive of
      recurrence than the presence of LOH at any one particular locus. Moreover, the
      identification of a threshold of LOH could help in predicting patients with poor
      outcome who may be candidates for local or systemic adjuvant therapies.

PMID- 15869993
TI  - Combination chemotherapy with docetaxel, estramustine and suramin for hormone
      refractory prostate cancer.
AB  - PURPOSE: To investigate more effective chemotherapy against hormone refractory
      prostate cancer (HRPC) with the combination of estramustine (EM), docetaxel, and
      suramin. PATIENTS AND METHODS: A total of 42 patients with symptomatic,
      progressive HRPC were included in this study. We evaluated the activity of the
      following schedule: EM 10 mg/kg orally daily on Days 1 to 21 every 28 days,
      docetaxel 70 mg/m(2) IV on Day 2 every 28 days and a total doses of 2150 mg of
      suramin in every cycle. Treatment was continued until disease progression or
      excessive toxicity. RESULTS: Median follow-up was 23.4 months. A median of 8.8
      consecutive cycles was administered per patient. In the 25 patients with
      lymphadenopathy, there were three (12%) complete and 18 (72%) partial responses
      for a measurable disease response rate of 84%. Levels of prostatic specific
      antigen (PSA) decreased by greater than 50% in 100% of patients and by greater
      than 90% in 76.2%. The median time to progression was 57 weeks and median overall
      survival was 132 weeks. A decline in PSA of > or =50% lasting > or =30 days was
      significantly associated with a prolonged median time to progression and median
      overall survival. Tumor volume reduction and/or antitumor treatment effects were
      observed in 88% of patients. A significant decrease in mean pain score from 7.8
      (range, 6-10) to 2.2 (range, 0-4) (P < 0.001) was achieved in 78%. Of patients
      with bone metastasis, 30.5% demonstrated a partial response. The mean Eastern
      Cooperative Oncology Group (ECOG) performance score improved from 2.8 to 1.5 at
      the end of treatment period. There was no therapy-related death. The predominant
      toxicities were Grade 3 or 4 leukopenia in 33.3%, anemia in 21%, thrombocytopenia
      in 21.4%, cardiac ischemia in 4.7%, and rash in 4.7%. CONCLUSION: The combination
      of docetaxel, EM, and suramin is a highly effective regimen for HRPC. Although
      hematologic and gastrointestinal toxicities were modest, these were easily
      managed medically.

PMID- 15869994
TI  - Use of polymerase chain reaction analysis of urinary DNA to detect bladder
      carcinoma.
AB  - A cohort of 113 patients underwent prospective evaluation with a panel of seven
      microsatellites, on chromosomes 9, 13 and 17. Thirty-seven patients had
      histologically confirmed bladder tumors, 53 patients had a history of previous
      transitional cell carcinoma of the bladder (TCC) but normal cystoscopies (control
      Group 1), and 23 patients had no previous history of TCC and normal cystoscopies
      (control Group 2). Urinary DNA was considered to show a deletion if an allele was
      reduced by more than 50%, and this was considered diagnostic of bladder
      carcinoma. The sensitivity of the method was 50%, positive predictive value was
      80%, and specificity was 93%. Reducing the threshold for defining allelic loss
      increases sensitivity, but reduces specificity. The concentration of urinary DNA
      in the sample did not influence detection rate. The grade and stage of the
      bladder tumor did not influence the likelihood of detection. This method detects
      bladder carcinoma with high specificity, and increasing the number of
      microsatellites used should increase sensitivity.

PMID- 15869995
TI  - A prospective clinical trial of green tea for hormone refractory prostate cancer:
      an evaluation of the complementary/alternative therapy approach.
AB  - PURPOSE: To evaluate the efficacy and toxicity of green tea, prescribed as an
      alternative complementary (CAM) formulation on hormone refractory prostate cancer
      (HRPC). METHODS: Patients with HRCP were prescribed green tea extract capsules at
      a dose level of 250 mg twice daily. Efficacy and toxicity were evaluated during
      monthly visits. The primary endpoint was prostate-specific antigen (PSA) or
      measurable disease progression after a minimum of 2 months of therapy. RESULTS:
      Nineteen patients were enrolled into the study. The treatment was generally well
      tolerated. Twelve patients reported at least one side effect; only two of these
      were of moderate or severe grade. Primary toxicity was related to
      gastrointestinal irritation or caffeine intake. Four patients did not complete
      the minimum 2 months of therapy because of: intolerance (two patients), physician
      stoppage (one patient), death from cerebrovascular accident (one patient).
      Fifteen patients completed at least 2 months of therapy. Nine of these patients
      had progressive disease within 2 months of starting therapy. Six patients
      developed progressive disease after additional 1 to 4 months of therapy.
      CONCLUSION: Green tea, as CAM therapy, was found to have minimal clinical
      activity against hormone refractory prostate cancer.

PMID- 15869996
TI  - Endoscopic treatment of upper tract transitional cell carcinoma.
AB  - PURPOSE: To review the current literature and data describing primary endoscopic
      treatment of upper tract transitional cell carcinoma (TCC). MATERIALS AND
      METHODS: Published, peer-reviewed articles on ureteroscopic, percutaneous, and
      laparoscopic treatment of upper tract TCC were identified using the MEDLINE
      database. RESULTS: Nephroureterectomy has been considered the "gold standard" for
      upper tract TCC. Minimally invasive approaches, initially advocated for patients
      requiring a nephron sparing approach (i.e., solitary kidney or renal
      insufficiency) or those with significant comorbidities precluding definitive
      surgery, have been increasingly used with the further refinement of ureteroscopy,
      percutaneous renal surgery, and laparoscopy. Ureteroscopy has been used
      successfully, resulting in recurrence rates ranging from 31% to 65% and disease
      free rates of 35% to 86%. Progression and metastatic rates are low and correlate
      with tumor grade. Likewise, percutaneous approaches show disease specific
      survival and recurrence rates correlating with tumor grade. Patients with low
      grade tumors (Grades 1-2) do well with this approach with recurrence rates and
      disease specific survival rates of 26% to 28% and 96% to 100%, respectively. For
      those patients requiring complete extirpation of the kidney and ureter,
      laparoscopic nephroureterectomy results in decreased postoperative pain, shorter
      hospital stay, and more rapid convalescence without compromising cancer control.
      CONCLUSIONS: Nephron sparing approaches in well-selected patients with low stage
      and low-grade disease can be treated endoscopically with ureteroscopy and
      percutaneous renal surgery. Laparoscopic nephroureterectomy offers a safe,
      minimally invasive alternative to traditional open surgical techniques for
      patients with TCC of the upper urinary tract.

PMID- 15869997
TI  - Influence of p53 and bcl-2 on chemosensitivity in benign and malignant prostatic
      cell lines.
AB  - The administration of cancer chemotherapeutic agents results in an increase in
      the apoptotic cells in the tumor: therefore, it has been assumed that anticancer
      drugs exhibit their cytotoxic effects via apoptotic signaling pathways.
      Characteristics that confer sensitivity to drug-induced apoptosis are, a
      functional p53 protein and expression of the apoptosis-promoting protein, bax.
      The role of p53 and bax/bcl-2 in drug-induced apoptosis was assessed in six
      prostate cell lines, 1532T, 1535T, 1542T, 1542N, BPH-1 and LNCaP using TD(50)
      concentrations of etoposide, vinblastine and estramustine. Cell death was
      monitored morphologically by fluorescent microscopy, and by flow cytometry
      (Annexin-V assay). Apoptotic morphology was rather low and ranged from 0.1% to
      12.1%, 3.0% to 6.0% and 0.1% to 8.5% for etoposide, estramustine and vinblastine,
      respectively. Annexin-V binding and flow cytometry indicated apoptotic
      propensities of 0% to 4%, 0% to 3% and 0% to 5%, respectively. The percentage of
      cells responding to drug-induced apoptosis was, on average, higher in the tumor
      cell lines than in the normal cell lines, but showed no correlation with p53
      status. The percentage of cells showing necrosis, assessed by Annexin binding and
      Propidium Iodide permeability in aqueous medium, tended to be much higher, and
      was found to be at the level of 5% to 30%. Immunoblotting demonstrated that bax
      and bcl-2 proteins were expressed at a basal level in all cell lines, but did not
      increase after exposure to TD(50) doses of the three drugs. The ratio of bax and
      bcl-2, measured by laser scanning densitometry, was not altered by the drug
      induced DNA damage. The results suggest that apoptosis is not a major mechanism
      of drug-induced cell death in prostate cell lines and appears to be independent
      of p53 status and bax/bcl-2 expression.

PMID- 15869998
TI  - Metastatic penile cancer in a young Caucasian male: impact of delayed diagnosis.
AB  - Penile cancer is an uncommon malignancy in the developed world, with only 1200
      estimated cases per year in the United States. This is usually a cancer of older
      men and often the diagnosis is delayed because of lack of suspicion on the part
      of the patient or primary care provider. We report a case of penile cancer in a
      young Caucasian male in whom a delay in diagnosis had a deleterious impact on
      outcome. We describe and illustrate how, to palliate his symptoms, the patient
      required a hemipelvectomy plus a total pelvic exenteration. We present this case
      to alert physicians of the possibility of penile cancer in young Caucasian males
      as well as to demonstrate the significant morbidity and mortality that can ensue
      from a delay in diagnosis.

PMID- 15869999
TI  - Paratesticular desmoplastic small round cell tumor: case report.
AB  - BACKGROUND: The desmoplastic small round cell tumor has recently been separated
      from other small round cell tumors because of its characteristic pathological and
      clinical features. They are usually intra-abdominal tumors affecting young people
      and have classically been associated with a bad prognosis. However, in recent
      years there have reports on desmoplastic small round cell tumors affecting other
      body regions, including the paratesticular area. CASE PRESENTATION: We report the
      case of a 23-year-old male, that consulted on a progressive enlargement of the
      right hemiscrotum in the last year and a half. He referred no previous urological
      symptoms and had no systemic symptomatology. Physical examination revealed a
      round elastic firm 2 to 3 cm mass distal to the tail of the epididymis, which was
      excised with a preoperative diagnosis of adenomatoid tumor. However, histological
      and immunohistochemical diagnosis confirmed a desmoplastic small round cell
      tumor. The extension study included a computed tomography scan and a plain chest
      radiograph, that showed no metastasis. The patient received chemoradiation
      therapy with methotrexate, dacarbacin, cyclophosphamide, actinomycin D and
      vincristin, but had to be changed to a vincristin, actinomycin D,
      cyclophosphamide and adriamicin scheme on severe toxicity. He completed five
      cycles of the chemotherapy with moderate toxicity. Today, 6 years after diagnosis
      the patient remains well and free of disease. CONCLUSIONS: Recent reviews on
      desmoplastic small round cell tumor affecting the paratesticular area have shown
      a better prognosis for tumors of this origin compared to abdominal ones. We
      should include this lesion among the differential diagnosis of paratesticular
      tumors, mainly in children and adolescents.

PMID- 15870014
TI  - In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell
      proliferation.
AB  - Regulatory T cells (Tregs) have been shown to be critical in the balance between
      autoimmunity and tolerance and have been implicated in several human autoimmune
      diseases. However, the small number of Tregs in peripheral blood limits their
      therapeutic potential. Therefore, we developed a protocol that would allow for
      the expansion of Tregs while retaining their suppressive activity. We isolated
      CD4+CD25 hi cells from human peripheral blood and expanded them in vitro in the
      presence of anti-CD3 and anti-CD28 magnetic Xcyte Dynabeads and high
      concentrations of exogenous Interleukin (IL)-2. Tregs were effectively expanded
      up to 200-fold while maintaining surface expression of CD25 and other markers of
      Tregs: CD62L, HLA-DR, CCR6, and FOXP3. The expanded Tregs suppressed
      proliferation and cytokine secretion of responder PBMCs in co-cultures stimulated
      with anti-CD3 or alloantigen. Treg expansion is a critical first step before
      consideration of Tregs as a therapeutic intervention in patients with autoimmune
      or graft-versus-host disease.

PMID- 15870015
TI  - Functional analysis of highly defined, FACS-isolated populations of human
      regulatory CD4+ CD25+ T cells.
AB  - The importance of CD4+ CD25+ regulatory T cells (Treg) in maintaining immune
      homeostasis has been directly demonstrated in vivo by their manipulation in a
      number of autoimmune disease models in the mouse. In the study of human
      regulatory cells, we have found that the cells that consistently demonstrate the
      in vitro regulatory activity most similar to that described for murine cells in
      vitro are best identified by restricting the isolation of CD25+ CD4 T cells to
      those cells expressing only the highest levels of CD25, representing
      approximately 2-3% of total CD4 T cells. Thus, it is the CD4+ CD25high subset
      that exhibits the in vitro characteristics that are identical to the CD4+ CD25+
      regulatory cells initially characterized in mice. Furthermore, the cells
      expressing medium to low levels of CD25 not only do not exhibit suppressive
      activity directly ex vivo, but also actually contain a significant proportion of
      CD62L- CD4 T cells which are believed to be in vivo activated T cells. Due to the
      inherent difficulties in using CD25 as a marker for the purification of Treg
      cells, the finding that selection of the CD25high subset of CD4+ CD25+ T cells
      minimizes the co-isolation of contaminating activated CD4 T cells is important
      for future studies of these Treg cells in human disease. In order to perform
      these studies, we first had to establish a highly reproducible 'micro in vitro co
      culture' assay system to enable the functional analysis of high-purity, but low
      yield regulatory populations derived from FACS sorting. With this system in
      place, we are poised to dissect the potential heterogeneity of mechanisms
      employed by highly specific subpopulations of CD4+ CD25+ cells.

PMID- 15870016
TI  - Regulation of immune and autoimmune responses by ICOS-B7h interaction.
AB  - Proper T cell activation and function are regulated by the innate immune system,
      importantly through positive and negative costimulatory molecules of the B7
      superfamily. Inducible costimulator (ICOS) is expressed on T cells after T cell
      activation. A ligand for ICOS, B7h (also known as B7RP-1), is expressed on B
      cells and induced in nonlymphoid tissues by TNF-alpha. The wide distribution of
      B7h may play essential roles in different phases and types of immune function. In
      this review, we summarize the latest data about inducible costimulator and its
      receptor and their roles in regulation of immune and autoimmune responses.

PMID- 15870017
TI  - Suppression of HIV-1 infection in primary CD4 T cells transduced with a self
      inactivating lentiviral vector encoding a membrane expressed gp41-derived fusion
      inhibitor.
AB  - Peptidomimetics of HIV-1 gp41 sequences required for membrane fusion are potent
      inhibitors of HIV-1 entry. We hypothesize that expression of a membrane-bound
      gp41-derived fusion inhibitor will confer HIV-1 resistance to primary CD4 T
      cells. Efficient gene delivery and stable expression of a membrane-bound gp41
      derived fusion inhibitor to primary CD4 T cells was accomplished using a self
      inactivating lentiviral vector. A potent antiviral effect was observed when
      transduced CD4 T cells were challenged with a highly virulent CXCR4-tropic strain
      of HIV-1. Production of soluble p24 in the supernatant was inhibited 100-fold,
      and cytopathic effects were evident early in non-transduced cells and absent in
      transduced cells. Expression of the gp41 sequences was not detrimental to CD4
      cells as transduced CD4 T cells exhibited a population doubling time that was
      equivalent to T cells transduced with a control vector. Results from this study
      support the rationale to use this lentiviral vector targeted at HIV entry as a
      potential gene therapy for HIV infection.

PMID- 15870018
TI  - The CATERPILLER family: an ancient family of immune/apoptotic proteins.
AB  - Ancient immune pathways in other species have provided clues for the discovery of
      important molecules in the mammalian immune system. A notable example is the
      discovery of Toll-like receptors based on the Toll receptors in Drosophila. In
      plants, a subclass of the disease resistance (R) genes is crucial for immune
      defense against a host of insults. This R gene subclass encodes a combined
      nucleotide-binding domain/leucine rich region (NBD/LRR) motif. Intriguingly,
      proteins with such a motif are found in mammalians, and several are also shown to
      be important in inflammatory and immune responses. This family, which we
      designated as the CATERPILLER (CARD, Transcription Enhancer, R (purine)-binding,
      Pyrin, Lots of Leucine Repeats) gene family while others have designated it as
      the NOD family, has over 20 members. They are crucial in the control of
      cytokines, inflammatory responses, NF-kappaB activation, and likely cell death
      and survival. Several prominent members including CIITA, CIAS1, and NOD2 are
      linked to immunologic genetic disorders that are hereditary. This indicates that
      these genes are ancient and important regulators of the immune system.

PMID- 15870019
TI  - Toll-like receptors in giant cell arteritis.
AB  - Giant cell arteritis, a primary vasculitis of medium-sized and large arteries,
      causes vessel occlusion through fast and concentric intimal hyperplasia.
      Contextual parameters, especially the topography of the arterial wall, have
      emerged as critical pathogenic elements. Experimental data support the concept
      that the disease is initiated in the most outer layer of the arterial wall, the
      adventitia. CD4 T cells are recruited to the adventitia, undergo local activation
      and subsequently orchestrate macrophage differentiation. T cells and macrophages
      infiltrate into all wall layers and acquire different effector functions
      dependent on cues in their immediate microenvironment. The end result is
      myofibroblastic proliferation, luminal stenosis, and tissue ischemia. Adaptive
      immune responses in the adventitia are triggered by a population of indigenous
      dendritic cells (DC) placed at the adventitia-media junction. These arterial DCs
      have a unique surface receptor profile, including a series of Toll-like receptors
      (TLR). Responsiveness of such arterial DCs to blood-borne stimuli has been
      studied in human arteries engrafted into immunodeficient mice. Ligands of TLR4
      are able to start maturation of adventitial DCs which fail to leave the
      peripheral tissue site. Instead, these adventitial DCs produce chemokines,
      recruit T cells, and support their local activation. These data identify tissue
      residing DCs as gatekeepers in vasculitis and support the model that TLR ligands
      function as instigators of vessel wall inflammation.

PMID- 15870020
TI  - Granulation tissue formation by nonspecific inflammatory agent occurs
      independently of macrophage galactose-type C-type lectin-1.
AB  - The role of a macrophage galactose-type calcium-type lectin-1 (MGL1) in antigen
      independent granulation tissue formation was investigated. Granulation tissue was
      induced by injection of carrageenan in an air pouch and distribution of
      macrophages expressing MGL1/2 was histologically examined. MGL1/2-positive cells
      were not observed in the granulation tissue induced by carrageenan though these
      cells were present in dermis. This was distinct from the fact that MGL1/2
      positive cells were abundant in granulation tissue induced by antigenic
      stimulation. CD11b-positive cells were in dermis and carrageenan-induced
      granulation tissue. Because antigen-induced granulation tissue formation was
      previously shown to decrease in MGL1-deficient mice or after treatment with anti
      MGL1 antibody, we investigated the effects of MGL1-deficient status on
      carrageenan-induced granulation tissue formation. The thickness of granulation
      tissue was almost identical between wild-type and MGL1-deficient mice. It is
      highly likely that MGL1-positive cells are not involved in tissue remodeling when
      inflammation is driven by nonspecific stimuli.

PMID- 15870021
TI  - Anti-IL-5 and hypereosinophilic syndromes.
AB  - Hypereosinophilic syndromes represent a heterogeneous group of disorders
      characterized by peripheral eosinophilia and end-organ damage associated with
      eosinophil infiltrations. In many instances, the eosinophilia is refractory to
      standard therapies and clinicians rely on potentially toxic alternatives. This
      group of disorders has recently gained attention with the description of patients
      that harbor a genetic rearrangement that produces a constitutively active
      tyrosine kinase, often responsive to anti-tyrosine kinase therapy. In addition,
      the recent expansion in our understanding of the mechanisms by which eosinophils
      develop and become activated, involving the cytokine interleukin-5 (IL-5), has
      led to advances in therapeutic options. A new therapy currently in clinical
      trials is the humanized monoclonal antibody against IL-5. This review will
      discuss the etiology, classification, and treatment options for the
      hypereosinophilic syndromes, with particular emphasis on anti-interleukin-5
      therapy.

PMID- 15870022
TI  - Rapid emergence of escape mutants following infection with murine cytomegalovirus
      in immunodeficient mice.
AB  - Natural killer (NK) cells play a crucial role in the initial host defense against
      pathogens such as murine cytomegalovirus (MCMV). They respond rapidly and
      effectively control pathogen replication while the adaptive immune system is
      being activated. However, in the absence of an adaptive immune system, an
      effective initial NK cell response is not sufficient for long-term pathogen
      control as demonstrated by the late recrudescence of disease and mortality in
      immunodeficient mice infected with MCMV. In this setting, NK cells suppress the
      initial infection but exert enough selective pressure to drive the outgrowth of
      MCMV mutants that escape recognition by NK cells. Herein, we characterize the
      rapid emergence of escape mutants following infection with a plaque-purified MCMV
      isolate and demonstrate that these mutant viruses are no longer effectively
      controlled by NK cells. These findings suggest that late recrudescence of viral
      infections in certain clinical settings may also be due to viral escape from NK
      cells or other components of innate immunity.

PMID- 15870023
TI  - Evolution of a T-B- SCID into an Omenn syndrome phenotype following parainfluenza
      3 virus infection.
AB  - Mutations in both of the recombination activating genes (RAG)1 and RAG2 can lead
      to either T-B-severe combined immune deficiency (SCID) or Omenn syndrome (OS),
      two diseases presenting with totally different clinical and laboratory
      manifestations. The fact that the same mutations can cause either T-B- SCID or
      OS, even within the same family, lends credibility to the hypothesis that an
      additional factor (autoantigen or exoantigen) is required in certain
      circumstances for the development of OS phenotype. We investigated three patients
      from the same extended family who presented as T-B- SCID due to a homozygous
      mutation (G1305T) in the RAG2 gene. Our data support the notion that mutated RAG
      proteins may not always be sufficient to cause OS phenotype, and show evolution
      from a T-B- SCID into a typical OS phenotype subsequent to parainfluenza 3 virus
      infection.

PMID- 15870024
TI  - IL-18 binding protein fusion construct delays the development of diabetes in
      adoptive transfer and cyclophosphamide-induced diabetes in NOD mouse.
AB  - IL-18 is a type 1 pro-inflammatory cytokine with structural similarities to IL-1
      and in synergy with IL-12 stimulates IFN-gamma production from T lymphocytes and
      polarizes development and function of Th1 cells. Because IL-1, IFN-gamma, and up
      regulated Th1-mediated events are involved in the pathogenesis of both human and
      rodent type 1 diabetes mellitus, we have evaluated the effects of a specific
      inhibitor of IL-18 (the IL-18bp:FcIg) on the development of accelerated forms of
      autoimmune diabetes in NOD mice. The data show that prolonged prophylactic
      treatment with IL-18bp:FcIg significantly reduced the cumulative incidence of
      diabetes induced in NOD mice either by adoptive transfer of diabetogenic cells or
      by injection with large doses of cyclophosphamide. These data provide the first
      in vivo evidence for the diabetogenic role of IL-18 in immuno-inflammatory
      diabetogenic pathways in NOD mice.

PMID- 15870025
TI  - C3 is central to the interstitial component of experimental immune complex
      glomerulonephritis.
AB  - We have suggested that renal tubular synthesis of C3 and its activation in the
      cortical interstitium is a mechanism for the progression of glomerulonephritis to
      interstitial injury. To test this hypothesis, immune complex glomerulonephritis
      was induced in C57BL/6 mice by intraperitoneal injections of horse spleen
      apoferritin and lipopolysaccharide (HSA/LPS). When compared to wild-type (WT)
      animals, C3 knockout (C3KO) mice had glomerular changes that were identical.
      Morphometric analysis of the cortical interstitium, however, showed marked
      differences. WT mice had more interstitial inflammation, edema, and tubular
      atrophy, when compared to C3KO mice. At the end of the experiment, WT animals
      also had significantly more proteinuria than did C3KOs. These experiments provide
      further evidence of a role of locally synthesized complement in the progression
      of glomerular disease.

PMID- 15870026
TI  - Prostaglandin E1-initiated immune regulation during human mixed lymphocyte
      reaction.
AB  - Prostaglandin E1 (PGE1) has therapeutic value for transplantations due to its
      microvascular activity. Interleukin (IL)-18, which is elevated in plasma during
      the acute rejection after organ transplantation, elicits the expression of
      intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand
      (CD40L) on monocytes as well as the production of interferon (IFN)-gamma and IL
      12 and proliferation of T-cells during the human mixed lymphocyte reaction (MLR)
      in an in vitro model of acute rejection. In contrast, PGE1 inhibits all the
      adhesion molecule expression, cytokine production and T-cell proliferation in the
      presence of IL-18. The effects of PGE1 depend on stimulation of the IP/EP2/EP4
      receptor, and thus, PGE1 might have therapeutic potential for treating acute
      rejection due to its immune regulatory effect.

PMID- 15870027
TI  - Angiopoietin-like-4 is a potential angiogenic mediator in arthritis.
AB  - Our previous studies of gene expression profiling during collagen-induced
      arthritis (CIA) indicated that the putative angiogenic factor Angptl4 was one of
      the most highly expressed mRNAs early in disease. To investigate the potential
      involvement of Angptl4 in CIA pathogenesis, Angptl4 protein levels were assessed
      at early stages of disease and its cellular sources were determined. In addition,
      the functional effects of mouse Angptl4 on endothelial cells were assessed.
      Angptl4 protein levels were higher in arthritic joints as compared to normal
      joints. In situ hybridization localized Angptl4 mRNA to stromal fibroblast-like
      cells within the inflamed synovium. Temporal expression of Angptl4 mRNA during
      CIA was similar to that of key angiogenic factors, including structurally related
      angiopoietin 1. Recombinant mouse Angptl4 promoted endothelial cell survival and
      formation of tubule-like structures. These functional effects of Angptl4,
      combined with very high expression at early stages of CIA, suggest a role for
      Angptl4 in angiogenesis in arthritis.

PMID- 15870028
TI  - Islet-cell antigen-reactive T cells show different expansion rates and Th1/Th2
      differentiation in type 1 diabetic patients and healthy controls.
AB  - The low frequency of islet-cell antigen-reactive T cells in type 1 diabetes makes
      their direct measurement difficult. Commonly used in vitro expansion could alter
      in vivo frequencies and Th1/Th2 differentiation states. Using IFN-gamma/IL-4
      double color ELISPOT, we tested longitudinally the reactivity of PBMC from HLA
      matched diabetic patients and healthy controls to GAD65, IA-2, and proinsulin
      peptides ex vivo and after in vitro culture. The peptide-reactive T cells showed
      IFN-gamma bias in the patients' PBMC in the primary assay. During in vitro
      culture, both IFN-gamma- and IL-4-producing cells were induced in controls,
      suggesting that the precursor cells were uncommitted naive T cells in vivo. In
      contrast, in diabetic patients, the ex vivo IFN-gamma response was conserved
      during culture, suggesting their Th1 commitment. Using CFSE-dye-dilution, we
      demonstrate that naive T cells expand in vitro at a faster rate than memory
      cells, which might account for the differences in expansion rates between
      diabetic patients and controls.

PMID- 15870029
TI  - Environmental influences during development and their later consequences for
      health and disease: implications for the interpretation of empirical studies.
AB  - Early experience has a particularly great effect on most organisms. Normal
      development may be disrupted by early environmental influences; individuals that
      survive have to cope with the damaging consequences. Additionally, the responses
      required to cope with environmental challenges in early life may have long-term
      effects on the adult organism. A further set of processes, those of developmental
      plasticity, may induce a phenotype that is adapted to the adult environment
      predicted by the conditions of early life. A mismatch between prediction and
      subsequent reality can cause severe health problems in those human societies
      where economic circumstances and nutrition are rapidly improving. Understanding
      the underlying mechanisms of plasticity is, therefore, clinically important.
      However, to conduct research in this area, developmental plasticity must be
      disentangled from disruption and the adverse long-term effects of coping. The
      paper reviews these concepts and explores ways in which such distinctions may be
      made in practice.

PMID- 15870031
TI  - Transmission dynamics of parasitic sea lice from farm to wild salmon.
AB  - Marine salmon farming has been correlated with parasitic sea lice infestations
      and concurrent declines of wild salmonids. Here, we report a quantitative
      analysis of how a single salmon farm altered the natural transmission dynamics of
      sea lice to juvenile Pacific salmon. We studied infections of sea lice
      (Lepeophtheirus salmonis and Caligus clemensi) on juvenile pink salmon
      (Oncorhynchus gorbuscha) and chum salmon (Oncorhynchus keta) as they passed an
      isolated salmon farm during their seaward migration down two long and narrow
      corridors. Our calculations suggest the infection pressure imposed by the farm
      was four orders of magnitude greater than ambient levels, resulting in a maximum
      infection pressure near the farm that was 73 times greater than ambient levels
      and exceeded ambient levels for 30 km along the two wild salmon migration
      corridors. The farm-produced cohort of lice parasitizing the wild juvenile hosts
      reached reproductive maturity and produced a second generation of lice that re
      infected the juvenile salmon. This raises the infection pressure from the farm by
      an additional order of magnitude, with a composite infection pressure that
      exceeds ambient levels for 75 km of the two migration routes. Amplified sea lice
      infestations due to salmon farms are a potential limiting factor to wild salmonid
      conservation.

PMID- 15870030
TI  - The effect of the Neolithic expansion on European molecular diversity.
AB  - We performed extensive and realistic simulations of the colonization process of
      Europe by Neolithic farmers, as well as their potential admixture and competition
      with local Palaeolithic hunter-gatherers. We find that minute amounts of gene
      flow between Palaeolithic and Neolithic populations should lead to a massive
      Palaeolithic contribution to the current gene pool of Europeans. This large
      Palaeolithic contribution is not expected under the demic diffusion (DD) model,
      which postulates that agriculture diffused over Europe by a massive migration of
      individuals from the Near East. However, genetic evidence in favour of this model
      mainly consisted in the observation of allele frequency clines over Europe, which
      are shown here to be equally probable under a pure DD or a pure acculturation
      model. The examination of the consequence of range expansions on single
      nucleotide polymorphism (SNP) diversity reveals that an ascertainment bias
      consisting of selecting SNPs with high frequencies will promote the observation
      of genetic clines (which are not expected for random SNPs) and will lead to
      multimodal mismatch distributions. We conclude that the different patterns of
      molecular diversity observed for Y chromosome and mitochondrial DNA can be at
      least partly owing to an ascertainment bias when selecting Y chromosome SNPs for
      studying European populations.

PMID- 15870032
TI  - Evidence for recombination in scorpion mitochondrial DNA (Scorpiones: Buthidae).
AB  - There has been very little undisputed evidence for recombination in animal
      mitochondrial DNA (mtDNA) provided so far. Previous unpublished results
      suggestive of mtDNA recombination in the scorpion family Buthidae, together with
      cytological evidence for a unique mechanism of mitochondrial fusion in that
      family, prompted us to investigate this group in more details. First, we
      sequenced the complete mtDNA genome of Mesobuthus gibbosus, and chose two genes
      opposing each other (16S and coxI). We then sequenced 150 individuals from the
      natural populations of four species of Buthidae (Old World genera Buthus and
      Mesobuthus). We observed strong evidence for widespread recombination through
      highly significant negative correlations between linkage disequilibrium and
      physical distance in three out of four species. The evidence is further confirmed
      when using five other tests for recombination and by the presence of a high
      amount of homoplasy in phylogenetic trees.

PMID- 15870033
TI  - Amplification of individual preferences in a social context: the case of wall
      following in ants.
AB  - Amplification processes are an essential component of the collective phenomena
      observed in social and gregarious species. In this paper, we tested the
      hypothesis that a weak individual wall-following tendency in ants can be
      amplified by communication through chemical trails, leading to a response to the
      spatial heterogeneities at the collective level. In our experiments, ants had to
      cross a diamond-shaped bridge along either of two branches of equal length to get
      from their nest to a food source. Two types of bridge were used: control bridges
      without a wall, and experimental bridges equipped with a wall along the inner
      edge of one of their branches. On the control bridges, ants collectively chose
      either branch of the bridge in most experiments, whereas on the experimental
      bridges, the branch with the wall was selected almost systematically. A
      mathematical model is proposed to assess, in various conditions, the importance
      of the amplification effect of the chemical trail on the wall-following tendency
      observed at the individual level. The model highlights the fact that the
      amplification process can lead to an overestimation of individual capabilities
      and, thus, that the results of experiments investigating individual preferences
      at group level in animals must be interpreted with caution.

PMID- 15870034
TI  - Flexibility of spatial averaging in visual perception.
AB  - The classical receptive field (RF) concept-the idea that a visual neuron responds
      to fixed parts and properties of a stimulus-has been challenged by a series of
      recent physiological results. Here, we extend these findings to human vision,
      demonstrating that the extent of spatial averaging in contrast perception is also
      flexible, depending strongly on stimulus contrast and uniformity. At low
      contrast, spatial averaging is greatest (about 11 min of arc) within uniform
      regions such as edges, as expected if the relevant neurons have orientation
      selective RFs. At high contrast, spatial averaging is minimal. These results can
      be understood if the visual system is balancing a trade-off between noise
      reduction, which favours large areas of averaging, and detail preservation, which
      favours minimal averaging. Two distinct populations of neurons with hard-wired
      RFs could account for our results, as could the more intriguing possibility of
      dynamic, contrast-dependent RFs.

PMID- 15870035
TI  - Winter availability of cereal stubbles attracts declining farmland birds and
      positively influences breeding population trends.
AB  - Many studies have demonstrated the selection of stubble fields by farmland birds
      in winter, but none have shown whether provisioning of this key habitat
      positively influences national population trends for widespread farmland birds.
      We use two complementary extensive bird surveys undertaken at the same localities
      in summer and winter and show that the area of stubble in winter attracts
      increased numbers of several bird species of conservation concern. Moreover, for
      several farmland specialists, the availability of stubble fields in winter
      positively influenced the 10 year breeding population trend (1994-2003) whereas
      hedgerow bird species were less affected. For skylarks and yellowhammers,
      initially negative trends showed recovery with 10-20 ha of stubble per 1 km
      square. Thus, agri-environment schemes that promote retention of over-winter
      stubbles will attract birds locally and are capable of reversing current
      population declines if stubbles are available in sufficient quantity.

PMID- 15870036
TI  - Directionality theory: a computational study of an entropic principle in
      evolutionary processes.
AB  - Analytical studies of evolutionary processes based on the demographic parameter
      entropy-a measure of the uncertainty in the age of the mother of a randomly
      chosen newborn-show that evolutionary changes in entropy are contingent on
      environmental constraints and can be characterized in terms of three tenets: (i)
      a unidirectional increase in entropy for populations subject to bounded growth
      constraints; (ii) a unidirectional decrease in entropy for large populations
      subject to unbounded growth constraints; (iii) random, non-directional change in
      entropy for small populations subject to unbounded growth constraints. This
      article aims to assess the robustness of these analytical tenets by computer
      simulation. The results of the computational study are shown to be consistent
      with the analytical predictions. Computational analysis, together with
      complementary empirical studies of evolutionary changes in entropy underscore the
      universality of the entropic principle as a model of the evolutionary process.

PMID- 15870037
TI  - The dynamics of genetic and morphological variation on volcanic islands.
AB  - Oceanic archipelagos of volcanic origin have been important in the study of
      evolution because they provide repeated natural experiments allowing rigorous
      tests of evolutionary hypotheses. Ongoing volcanism on these islands may,
      however, affect the evolutionary diversification of species. Analysis of
      population structure and phylogeographic patterns in island populations can
      provide insight into evolutionary dynamics on volcanic islands. We analysed
      genetic and morphological variation in the gecko Tarentola boettgeri on the
      island of Gran Canaria and compared it with Tarentola delalandii on Tenerife, a
      neighbouring volcanic island of similar age but distinctly different geological
      past. Intraspecific divergence of mitochondrial haplotypes indicates long-term
      persistence of Tarentola on each island, with a phylogeographic signal left by
      older volcanic events. More recent volcanic eruptions (approximately 0.2 million
      years ago on Tenerife, approximately 2.2 million years ago on Gran Canaria) have
      left a signature of population expansion in the population genetic structure, the
      strength of which depends on the time since the last major volcanic eruption on
      each island. While these stochastic events have left traces in morphological
      variation in Tenerife, in Gran Canaria geographical variation was solely
      associated with environmental variables. This suggests that historically caused
      patterns in morphology may be overwritten by natural selection within 2 million
      years.

PMID- 15870038
TI  - MHC-based patterns of social and extra-pair mate choice in the Seychelles
      warbler.
AB  - The existence and nature of indirect genetic benefits to mate choice remain
      contentious. Major histocompatibility complex (MHC) genes, which play a vital
      role in determining pathogen resistance in vertebrates, may be the link between
      mate choice and the genetic inheritance of vigour in offspring. Studies have
      shown that MHC-dependent mate choice can occur in mammal and fish species, but
      little work has focused on the role of the MHC in birds. We tested for MHC
      dependent mating patterns in the Seychelles warbler (Acrocephalus sechellensis).
      There was no influence of MHC class I exon 3 variation on the choice of social
      mate. However, females were more likely to obtain extra-pair paternity (EPP) when
      their social mate had low MHC diversity, and the MHC diversity of the extra-pair
      male was significantly higher than that of the cuckolded male. There was no
      evidence that females were mating disassortatively, or that they preferred males
      with an intermediate number of MHC bands. Overall, the results are consistent
      with the 'good genes' rather than the 'genetic compatibility' hypothesis. As
      female choice will result in offspring of higher MHC diversity, MHC-dependent EPP
      may provide indirect benefits in the Seychelles warbler if survival is positively
      linked to MHC diversity.

PMID- 15870039
TI  - Life-history variation of a neotropical thrush challenges food limitation theory.
AB  - Since David Lack first proposed that birds rear as many young as they can
      nourish, food limitation has been accepted as the primary explanation for
      variation in clutch size and other life-history traits in birds. The importance
      of food limitation in life-history variation, however, was recently questioned on
      theoretical grounds. Here, we show that clutch size differences between two
      populations of a neotropical thrush were contrary to expectations under Lack's
      food limitation hypothesis. Larger clutch sizes were found in a population with
      higher nestling starvation rate (i.e. greater food limitation). We experimentally
      equalized clutches between populations to verify this difference in food
      limitation. Our experiment confirmed greater food limitation in the population
      with larger mean clutch size. In addition, incubation bout length and nestling
      growth rate were also contrary to predictions of food limitation theory. Our
      results demonstrate the inability of food limitation to explain differences in
      several life-history traits: clutch size, incubation behaviour, parental feeding
      rate and nestling growth rate. These life-history traits were better explained by
      inter-population differences in nest predation rates. Food limitation may be less
      important to life history evolution in birds than suggested by traditional
      theory.

PMID- 15870040
TI  - Coronary endarterectomy with beating heart in patients with diffuse atheromatous
      coronary artery disease and poor ventricular function: early and midterm results.
AB  - BACKGROUND: In this study, we retrospectively reviewed our experience with off
      pump coronary artery bypass grafting and coronary artery endarterectomy in
      patients with severely reduced left ventricular function and diffuse atheromatous
      coronary artery disease to evaluate the early and midterm results. METHODS:
      Between July 1998 and March 2004, 42 patients underwent off-pump myocardial
      revascularization with coronary artery endarterectomy. The mean age (+/-SD) for
      the 28 male and 14 female patients was 59 +/- 10.2 years. Twenty-seven patients
      (64.2%) had experienced a previous myocardial infarction, and 11 (26.2%) had
      undergone an operation on an emergency basis. All patients had an ejection
      fraction of less than 30%. The left anterior descending coronary artery was the
      most endarterectomized vessel (75% of patients). RESULTS: There were 5 early
      deaths (11%). Twenty-five (67.6%) of the surviving patients were symptom free,
      and 8 were in Canadian Cardiovascular Society classes II to IV. The ejection
      fraction improved after the operation in the 30 patients (71.42%) who underwent
      echocardiographic control and coronary angiography. The 28.4-month patency rate
      of the endarterectomized coronary arteries was 89%. The patency rates were 93.3%
      for the left internal thoracic artery-left anterior descending coronary artery
      and 88.8% for the right coronary artery. CONCLUSION: The results of this study
      show increased operative mortality and morbidity in patients requiring coronary
      artery endarterectomy. However, the early results and particularly the midterm
      survival rates, clinical status, and continued graft patency justify off-pump
      coronary artery endarterectomy in patients with severely depressed left
      ventricular function and diffuse coronary artery disease. Many of these patients
      have disease that would otherwise be inoperable.

PMID- 15870041
TI  - Simplified placement of multiple artificial mitral valve chords.
AB  - BACKGROUND: The use of artificial chords for the replacement of diseased mitral
      valve chordae and the correction of anterior and posterior leaflet prolapse is
      well described, although it is infrequently applied because of technical
      challenges. METHODS: A simplified approach to attaching the new chords to a
      single papillary muscle base within the left ventricle has been reported, and we
      present a series of 13 patients with moderate-severe mitral regurgitation (MR)
      who underwent chordal replacement using this improved technique. RESULTS: The MR
      grade by echocardiogram improved from 3.7 +/- 0.4 preoperatively to 1.0 +/- 0.8
      postoperatively. All patients were doing well at a mean follow-up interval of 285
      +/- 62 days. CONCLUSION: Chordal replacement for both anterior and posterior
      leaflet prolapse is an effective treatment for MR when combined with standard
      mitral valve repair techniques. The authors' technique of determining proper
      chordal height and placing multiple chordae is also discussed.

PMID- 15870042
TI  - A new PRECiSe (priming reduced extracorporeal circulation setup) minimizes the
      need for blood transfusions: first clinical results in coronary artery bypass
      grafting.
AB  - Hemodilution by the crystalloid priming volume of standard heart-lung machines in
      cardiac surgery is associated with impaired organ function and increased blood
      transfusion requirements. The aim of this study was to evaluate the effect of the
      use of the newly developed priming reduced extracorporeal circulation setup
      (PRECiSe) on perioperative hemodilution and transfusion requirements. In a
      matched prospective study, 40 patients who underwent operations with the PRECiSe
      in elective primary coronary artery bypass surgery were compared with 40 patients
      who underwent operations with the standard heart-lung machine. A significant
      reduction in final priming volume resulted in a significantly reduced degree of
      hemodilution and transfusion requirements during and after extracorporeal
      circulation. In the PRECiSe group, only 10% of the patients needed transfusions
      during their hospital stay, whereas 35% of the patients in the control group
      required any transfusion (P < .05). The average transfusion per patient was 0.16
      units in the PRECiSe group and 1.25 units in the control group (P < .05). The
      PRECiSe was demonstrated to be safe and effective in coronary artery bypass
      surgery with respect to transfusion requirements and hemodilution, as well as
      with regard to patient safety, as represented by perioperative myocardial
      performance.

PMID- 15870043
TI  - Left ventricular outflow tract false aneurysm late after aortic valve
      replacement.
AB  - We describe an unusual case of left ventricular outflow tract (LVOT)
      pseudoaneurysm late after aortic valve replacement. A 77-year-old man, who had
      undergone aortic valve replacement with mechanical prosthesis 7 years ago,
      presented, asymptomatic, with a transesophageal echocardiography (TTE) diagnosis
      of a large cavitary mass arising behind the aortic wall. The orifice of the
      pseudoaneurysm was successfully surgically closed and the aortic root
      reconstructed with cryopreserved homograft.

PMID- 15870044
TI  - Surgical coronary revascularization with or without mitral valve repair of severe
      ischemic dilated cardiomyopathy.
AB  - BACKGROUND: Because patients with dilated cardiomyopathy tend to have a poor
      prognosis with medical therapy, surgery with coronary bypass alone or associated
      with mitral valve repair should be a promising feasible therapeutic option. We
      evaluated the early effects of surgical coronary revascularization with or
      without mitral valve repair in patients with severe dilated ischemic
      cardiomyopathy. METHODS: The study group consisted of 38 patients aged 65 +/- 8
      years with severe dilated ischemic cardiomyopathy, chest pain, and heart failure.
      Twenty-four patients were in a New York Heart Association (NYHA) class > or =3,
      and 14 patients were in class 2. Twenty patients had a degree of mitral
      regurgitation defined as an effective regurgitant orifice > or =20 mm2. The mean
      values (+/-SD) of the EuroSCORE, which evaluates operative risk, were 5 +/- 2.2.
      Clinical and echocardiographic reevaluation followed at 6 months. RESULTS: All
      patients underwent coronary artery bypass surgery with a mean of 2.3 +/- 0.8
      grafts, and mitral valve repair with annuloplasty and Cosgrove ring insertion
      were performed in 20 patients. No deaths occurred during the operative period.
      Ten patients could not be reevaluated at 6 months, and 3 patients died (7.9%
      mortality). At 6 months, the end-systolic volumes in 15 patients who underwent
      coronary bypass plus mitral valve repair (group A) and in 13 patients who
      underwent coronary bypass alone (group B) decreased, respectively, from 139 +/-
      56 mL to 121 +/- 94 mL and from 122 +/- 48 mL to 96 +/- 36 mL (P < .05). The wall
      motion score index also decreased from 1.9 +/- 0.3 to 1.4 +/- 0.4 and from 2.1 +/
      0.3 to 1.8 +/- 0.2, respectively. The mean values of the ejection fraction, the
      peak early mitral inflow velocity, and the ratio of the peak early mitral inflow
      velocity to the peak late mitral inflow velocity increased significantly in both
      groups (P < .001, P < .01, and P < .05, respectively). The mean NYHA functional
      class significantly improved in both groups (P < .0001). CONCLUSIONS: In patients
      with severe ischemic dilated cardiomyopathy, surgical coronary revascularization
      can be safely carried out during the operative and early postoperative periods
      with low mortality rates. This procedure decreased left ventricular end-systolic
      volume, consistently increased contractility, and subsequently ameliorated the
      ejection fraction to produce improvements in clinical condition according to the
      NYHA functional class. Similar results have been obtained in patients who have
      undergone coronary bypass surgery and mitral valve repair, despite a higher
      operative risk and longer cardiopulmonary bypass circulation and aortic cross
      clamping times.

PMID- 15870045
TI  - Surgical treatment of lone atrial fibrillation in an awake patient.
AB  - Surgical treatment of atrial fibrillation recently gained new popularity since
      the introduction of different energy sources and the development of minimally
      invasive techniques as an alternative to the original "cut-and-sew" technique.
      However, closed-chest ablation procedures are not feasible in presence of
      pericardial or pleural adhesions. To our knowledge, this is the first report of
      surgical treatment of atrial fibrillation in a conscious patient by means of a
      high epidural anesthesia. Since evidence of fibrothorax was found, a conscious
      patient suffering from lone atrial fibrillation underwent a beating-heart
      pulmonary veins isolation with a microwave device through a standard sternotomic
      approach. At 6 months follow-up, the patient is in stable sinus rhythm, without
      any palpitation nor electrocardiographic evidence (Holter monitoring) of
      recurrent atrial fibrillation.

PMID- 15870046
TI  - The incidence of emboli during cardiac surgery: a histopathologic analysis of
      2297 patients.
AB  - OBJECTIVE: Manipulation of the atherosclerotic aorta during cardiac surgery is
      assumed to cause embolization, which can contribute to adverse outcomes.
      Recently, as a result of worldwide trials deploying the Embol-X intraaortic
      filter during cardiac surgery, such emboli were captured and processed for
      histopathologic analysis. METHODS: Filters with a pore size of 120 microns were
      placed in 2297 patients who underwent the following operations: coronary artery
      bypass grafting (CABG) (70%), valve (17%), combination CABG/valve (11%), and
      other (2%). RESULTS: The filters captured at least one embolus in 98% of the
      patients. An average of 8.3 particles was captured per filter (range of 0-74).
      The surface area of the emboli was on an average 5.8 mm2 (range of 0-188 mm2).
      Histologic analysis of the captured particles indicated that in 79% of the
      filters fibrous atheromata were noted, in 44% there were platelets and fibrin, 8%
      had red blood cell thrombus, 3% had fibro-fatty/adventitial tissue, 2% had other
      material including cartilage, myocardium, lung, suture, and a teflon pledget. Of
      the patients enrolled, 1569 were high-risk. The average number of particles
      captured in the high-risk patients was 8.5 versus 5.8 for the low- to moderate
      risk patients (P < .0001). Concomitantly,there was an increase in the embolic
      burden between the higher- and lower-risk patients (surface area 6.6 vs. 4.0 mm2,
      P < .0001). CONCLUSION: These data show the ubiquitous incidence of emboli during
      cardiac procedures. Intraaortic filtration should reduce adverse outcomes as was
      demonstrated for the high-risk patients in this study. Aortic manipulation during
      cardiac surgery can cause embolization and increase morbidity. The use of an
      intraaortic filter can decrease the embolic burden. We now report the
      histopathologic analysis of these emboli.

PMID- 15870047
TI  - Bridging process-based and empirical approaches to modeling tree growth.
AB  - The gulf between process-based and empirical approaches to modeling tree growth
      may be bridged, in part, by the use of a common model. To this end, we have
      formulated a process-based model of tree growth that can be fitted and applied in
      an empirical mode. The growth model is grounded in pipe model theory and an
      optimal control model of crown development. Together, the pipe model and the
      optimal control model provide a framework for expressing the components of tree
      biomass in terms of three standard inventory variables: tree height, crown height
      and stem cross-sectional area. Growth rates of the inventory variables and the
      components of biomass are formulated from a carbon balance. Fundamentally, the
      parameters of the model comprise physiological rates and morphological ratios. In
      principle, the values of these parameters may be estimated by lower-level process
      models. Alternatively, the physiological and morphological parameters combine,
      under reasonable assumptions, into a set of aggregate parameters, whose values
      can be estimated from inventory data with a statistical fitting procedure.

PMID- 15870049
TI  - Growth of advance regeneration of Norway spruce after clear-cutting.
AB  - We developed a basal area growth model for recovery of advance growth of Norway
      spruce trees after clear-cutting. Stem diameter growth at ground level and needle
      mass characteristics were measured on permanent sample plots in Estonia. Both
      tree ring analysis (destructive sampling on one sample plot) and yearly repeated
      measurement data (two plots) were used to quantify advance growth. Basal area
      growth of small trees was estimated by multiple regression analysis. Previous
      year basal area of the tree and basal area growth explained tree performance the
      next year. Tree needle-mass variables characterizing the acclimation status of
      the tree were included in the model as explanatory factors. Needle samples (one
      shoot from the upper third of each tree crown) were collected each year after the
      growth period from all sample trees. Needle masses of shoots from consecutive
      years were correlated and this variable was used as a predictor in the simulation
      model. Accelerating growth was observed in trees that exceeded the growth
      threshold in the year after release: the greater the needle mass per shoot, the
      greater the acceleration in growth. Competition among advance regeneration trees
      was included in the model: small trees under taller neighbors exhibited reduced
      growth. We found that trees released from a long period of heavy shade can
      survive, but the time needed for acclimation and resumption of competitive growth
      rates is considerably longer than for trees released from light shade. Such trees
      can be used for forest regeneration, but competition control (particularly
      reducing the proportion of fast-growing hardwoods) is required.

PMID- 15870048
TI  - Analysis of biomass accumulation and stem size distributions over long periods in
      managed stands of Pinus sylvestris in Finland using the 3-PG model.
AB  - We tested the performance of a process-based model (PBM) in relation to long-term
      mensuration data from two sites in Finland where the stands were up to 90 years
      old and had been thinned at approximately 5-year intervals over the last 50
      years. The PBM used was based on the 3-PG (Physiological Principles to Predict
      Growth) model developed by Landsberg and Waring (1997), with modifications in the
      biomass allocation routine, for which we used data and calculations by Vanninen
      (2003) to estimate the allocation coefficients and turnover rates. Site fertility
      was estimated in terms of known site-type characteristics. The model was
      evaluated in terms of stand development and its ability to simulate responses to
      thinning; stem numbers after thinning were specified at the dates when the
      thinning took place. Stand development in terms of basal area, volume and mean
      diameter at breast height, closely followed the measured characteristics of all
      stands. Foliage mass predictions were close to estimates obtained by an empirical
      method. The analysis shows that, under normal thinning regimes, a range of
      different thinning intensities can be adequately described using a simple
      multiplicative model relating the proportion of volume and foliage mass removed
      to the corresponding proportion of stem numbers. This model, together with stem
      allometry data, described the "growth" in mean diameter after thinning, which
      simply reflected the removal of the smaller trees. These results indicate that,
      with a single set of parameter values, 3-PG can provide good descriptions of the
      growth patterns of trees-in this case Pinus sylvestris L.-over long periods,
      including growth after repeated thinning. One of the outputs from the 3-PG model
      is mean stem diameter (B): we show that it is feasible to estimate stem size
      distributions, which changed considerably over the life of these stands, from B
      using the Weibull function. This shows that, given information about the Weibull
      parameters for particular species and cultural systems, it should be possible to
      use stem numbers and the B obtained from the 3-PG model to produce information
      about stem size distributions from simulated data.

PMID- 15870050
TI  - Estimating foliage biomass in Scots pine (Pinus sylvestris) and Norway spruce
      (Picea abies) plots.
AB  - Dynamic decomposition models are needed to estimate changes in the carbon stock
      of boreal soil because these changes are difficult to measure directly. An
      important aboveground carbon flux to the soil is foliage litterfall. To estimate
      this flux, both the amount and the turnover rate of the foliage biomass component
      must be known. Several methods for estimating foliage biomass of Scots pine
      (Pinus sylvestris L.) and Norway spruce (Picea abies (L.) Karst.), including
      biomass equations and biomass expansion factors (BEFs), were compared with
      predicted foliage biomass based on forest inventory plot-level measurements.
      Measured foliage biomass was up-scaled from the branch-level to the plot-level by
      combining forest inventory variables (diameter, height, height at the crown base
      and crown base diameter) based on the assumptions of pipe model theory. Combining
      the foliage biomass: cross-sectional area ratio with the forest inventory
      variables provided accurate estimates of foliage biomass at the plot-level for
      plots in southern Finland. The results emphasize the need to test biomass
      equations with independent data, especially when the equations applied are based
      on neighboring regions.

PMID- 15870051
TI  - Modeling climate change effects on the potential production of French plains
      forests at the sub-regional level.
AB  - We modeled the effects of climate change and two forest management scenarios on
      wood production and forest carbon balance in French forests using process-based
      models of forest growth. We combined data from the national forest inventory and
      soil network survey, which were aggregated over a 50 x 50-km grid, i.e., the
      spatial resolution of the climate scenario data. We predicted and analyzed the
      climate impact on potential forest production over the period 1960-2100. All
      models predicted a slight increase in potential forest yield until 2030-2050,
      followed by a plateau or a decline around 2070-2100, with overall, a greater
      increase in yield in northern France than in the south. Gross and net primary
      productivities were more negatively affected by soil water and atmospheric water
      vapor saturation deficits in western France because of a more pronounced shift in
      seasonal rainfall from summer to winter. The rotation-averaged values of carbon
      flux and production for different forest management options were estimated during
      four years (1980, 2015, 2045 and 2080). Predictions were made using a two
      dimensional matrix covering the range of local soil and climate conditions. The
      changes in ecosystem fluxes and forest production were explained by the
      counterbalancing effect of rising CO2 concentration and increasing water deficit.
      The effect of climate change decreased with rotation length from short rotations
      with high production rates and low standing biomasses to long rotations with low
      productivities and greater standing biomasses. Climate effects on productivity,
      both negative and positive, were greatest on high fertility sites. Forest
      productivity in northern France was enhanced by climate change, increasingly from
      west to east, whereas in the southwestern Atlantic region, productivity was
      reduced by climate change to an increasing degree from west to east.

PMID- 15870052
TI  - Using ergodic theory to assess the performance of ecosystem models.
AB  - Ecosystem simulation models are designed to assess the flux of energy, water,
      carbon and nitrogen according to a given vegetation type. The reliability of the
      modeled results is determined by model validations. Model validations are
      typically done using classical statistical methods like regression analysis of
      predicted versus observed values, paired t statistics and error assessment
      procedures to characterize the quality of current and future model predictions.
      All these validation efforts concentrate on static aspects of the model but fail
      to describe the model dynamics. In this paper, we introduce methods from ergodic
      theory to analyze the dynamic behavior of ecosystem models. We describe (1) how
      the attractor representation of model behavior can be reconstructed from a time
      series of model outputs, and (2) what we can learn from the attractor to assess
      the model dynamics. As an application example, we provide simulation results for
      two important pine forest ecosystems in Austria, i.e., 23 Cembran pine and 16
      Scots pine stands. These stands were simulated with three model
      parameterizations: one representing a generic, evergreen needle-leaf forest, and
      two species- specific parameter sets, one for Cembran pine and one for Scots
      pine. First, we applied standard validation methods to get static measures of
      model accuracy and precision. Next, we used ergodic theory to assess model
      dynamics. A comparison of both analyses reveals important issues related to model
      dynamics, such as the finding that the occurrence of instabilities in model
      behavior may not be detected by standard validation methods. Using ergodic
      theory, we were able to reconstruct the attractors of model behavior. In the
      attractor describing model dynamics for Cembran pine, simulated with the generic,
      evergreen needle-leaf forest parameter set, we detected instability in model
      behavior. We identified this instability as a riddled basin configuration, which
      is a strong indicator for the occurrence of a chaotic model behavior that may
      result in random predictions. Our results suggest that ergodic theory is a useful
      tool for assessing inconsistencies in the dynamics of ecosystem model simulations
      that have not been detected by standard statistical validation methods.

PMID- 15870053
TI  - On the validation of models of forest CO2 exchange using eddy covariance data:
      some perils and pitfalls.
AB  - With the widespread application of eddy covariance technology, long-term records
      of hourly ecosystem mass and energy exchange are becoming available for forests
      around the world. These data sets hold great promise for testing and validation
      of models of forest function. However, model validation is not a straightforward
      task. The goals of this paper were to: (1) review some of the problems inherent
      in model validation; and (2) survey the tools available to modelers to improve
      validation procedures, with particular reference to eddy covariance data. A
      simple set of models applied to a data set of ecosystem CO2 exchange is used to
      illustrate our points. The major problems discussed are equifinality,
      insensitivity and uncertainty. Equifinality is the problem that different models,
      or different parameterizations of the same model, may yield similar results,
      making it difficult to distinguish which is correct. Insensitivity arises because
      the major sources of variation in eddy covariance data are the annual and diurnal
      cycles, which are represented by even the most basic models, and the size of the
      response to these cycles can mask effects of other driving variables. Uncertainty
      arises from three main sources: parameters, model structure and data, each of
      which is discussed in turn. Uncertainty is a particular issue with eddy
      covariance data because of the lack of replicated measurements and the potential
      for unquantified systematic errors such as flux loss due to advection. We
      surveyed several tools that improve model validation, including sensitivity
      analysis, uncertainty analysis, residual analysis and model comparison.
      Illustrative examples are used to demonstrate the use of each tool. We show that
      simplistic comparisons of model outputs with eddy covariance data are
      problematic, but use of these tools can greatly improve our confidence in model
      predictions.

PMID- 15870054
TI  - Modeling annual production and carbon fluxes of a large managed temperate forest
      using forest inventories, satellite data and field measurements.
AB  - We evaluated annual productivity and carbon fluxes over the Fontainebleau forest,
      a large heterogeneous forest region of 17,000 ha, in terms of species
      composition, canopy structure, stand age, soil type and water and mineral
      resources. The model is a physiological process-based forest ecosystem model
      coupled with an allocation model and a soil model. The simulations were done
      stand by stand, i.e., 2992 forest management units of simulation. Some input
      parameters that are spatially variable and to which the model is sensitive were
      calculated for each stand from forest inventory attributes, a network of 8800
      soil pits, satellite data and field measurements. These parameters are: (1)
      vegetation attributes: species, age, height, maximal leaf area index of the year,
      aboveground biomass and foliar nitrogen content; and (2) soil attributes:
      available soil water capacity, soil depth and soil carbon content. Main outputs
      of the simulations are wood production and carbon fluxes on a daily to yearly
      basis. Results showed that the forest is a carbon sink, with a net ecosystem
      exchange of 371 g C m(-2) year(-1). Net primary productivity is estimated at 630
      g C m(-2) year(-1) over the entire forest. Reasonably good agreement was found
      between simulated trunk relative growth rate (2.74%) and regional production
      estimated from the National Forest Inventory (IFN) (2.52%), as well as between
      simulated and measured annual wood production at the forest scale (about 71,000
      and 68,000 m(3) year(-1), respectively). Results are discussed species by
      species.

PMID- 15870055
TI  - Uncertainty in eddy covariance measurements and its application to physiological
      models.
AB  - Flux data are noisy, and this uncertainty is largely due to random measurement
      error. Knowledge of uncertainty is essential for the statistical evaluation of
      modeled and measured fluxes, for comparison of parameters derived by fitting
      models to measured fluxes and in formal data-assimilation efforts. We used the
      difference between simultaneous measurements from two towers located less than 1
      km apart to quantify the distributional characteristics of the measurement error
      in fluxes of carbon dioxide (CO2) and sensible and latent heat (H and LE,
      respectively). Flux measurement error more closely follows a double exponential
      than a normal distribution. The CO2 flux uncertainty is negatively correlated
      with mean wind speed, whereas uncertainty in H and LE is positively correlated
      with net radiation flux. Measurements from a single tower made 24 h apart under
      similar environmental conditions can also be used to characterize flux
      uncertainty. Uncertainty calculated by this method is somewhat higher than that
      derived from the two-tower approach. We demonstrate the use of flux uncertainty
      in maximum likelihood parameter estimates for simple physiological models of
      daytime net carbon exchange. We show that inferred model parameters are highly
      correlated, and that hypothesis testing is therefore possible only when the joint
      distribution of the model parameters is taken into account.

PMID- 15870056
TI  - Variability in net ecosystem exchange from hourly to inter-annual time scales at
      adjacent pine and hardwood forests: a wavelet analysis.
AB  - Orthonormal wavelet transformation (OWT) is a computationally efficient technique
      for quantifying underlying frequencies in nonstationary and gap-infested time
      series, such as eddy-covariance-measured net ecosystem exchange of CO2 (NEE). We
      employed OWT to analyze the frequency characteristics of synchronously measured
      and modeled NEE at adjacent pine (PP) and hardwood (HW) ecosystems. Wavelet
      cospectral analysis showed that NEE at PP was more correlated to light and vapor
      pressure deficit at the daily time scale, and NEE at HW was more correlated to
      leaf area index (LAI) and temperature, especially soil temperature, at seasonal
      time scales. Models were required to disentangle the impacts of environmental
      drivers on the components of NEE, ecosystem carbon assimilation (Ac) and
      ecosystem respiration (RE). Sensitivity analyses revealed that using air
      temperature rather than soil temperature in RE models improved the modeled
      wavelet spectral frequency response on time scales longer than 1 day at both
      ecosystems. Including LAI improved RE model fit on seasonal time scales at HW,
      and incorporating parameter variability improved the RE model response at annual
      time scales at both ecosystems. Resolving variability in canopy conductance,
      rather than leaf-internal CO2, was more important for modeling Ac at both
      ecosystems. The PP ecosystem was more sensitive to hydrologic variables that
      regulate canopy conductance: vapor pressure deficit on weekly time scales and
      soil moisture on seasonal to interannual time scales. The HW ecosystem was
      sensitive to water limitation on weekly time scales. A combination of intrinsic
      drought sensitivity and non-conservative water use at PP was the basis for this
      response. At both ecosystems, incorporating variability in LAI was required for
      an accurate spectral representation of modeled NEE. However, nonlinearities
      imposed by canopy light attenuation were of little importance to spectral fit.
      The OWT revealed similarities and differences in the scale-wise control of NEE by
      vegetation with implications for model simplification and improvement.

PMID- 15870057
TI  - A regression-based equivalence test for model validation: shifting the burden of
      proof.
AB  - Model validation is often realized as a test of how well model predictions match
      a set of independent observations. One would think that the burden of proof
      should rest with the model, to force it to show that it can make accurate
      predictions. Further, one would think that increasing the sample size ought to
      increase the model's ability to demonstrate its utility. Traditional statistical
      tools are inappropriate for this because they default to the case that the model
      and the data are no different, and their ability to detect differences increases
      with the sample size. These traditional tools are optimized to detect
      differences, rather than similarities. We present an alternative strategy for
      model validation that is based on regression and statistical tests of
      equivalence. Equivalence tests reverse the usual null hypothesis: they posit that
      the populations being compared are different and use the data to prove otherwise.
      In this sense, equivalence tests are lumping tests, whereas the traditional
      statistical tests are splitting tests. To date, model validation with equivalence
      tests has focused on comparisons of means. Our proposed test checks not only for
      similarity of means, but also for similarity between individual predictions and
      observations. The strategy is demonstrated using three case studies that differ
      in their modeling objectives, and for varied sample sizes. The proposed strategy
      provides a formal means of model validation that is superior to traditional
      statistical tests in each case.

PMID- 15870058
TI  - Bayesian calibration of process-based forest models: bridging the gap between
      models and data.
AB  - Process-based forest models generally have many parameters, multiple outputs of
      interest and a small underlying empirical database. These characteristics hamper
      parameterization. Bayesian calibration offers a solution to the calibration
      problem because it applies to models of any type or size. It provides parameter
      estimates, with measures of uncertainty and correlation among the parameters. The
      procedure begins by quantifying the uncertainty about parameter values in the
      form of a prior probability distribution. Then data on the output variables are
      used to update the parameter distribution by means of Bayes' Theorem. This yields
      a posterior calibrated distribution for the parameters, which can be summarized
      in the form of a mean vector and variance matrix. The predictive uncertainty of
      the model can be quantified by running it with different parameter settings,
      sampled from the posterior distribution. In a further step, one may evaluate the
      posterior probability of the model itself (rather than that of the parameters)
      and compare that against the probability of other models, to aid in model
      selection or improvement. Bayesian calibration of process-based models cannot be
      performed analytically, so the posterior parameter distribution must be
      approximated in the form of a representative sample of parameter values. This can
      be achieved by means of Markov Chain Monte Carlo simulation, which is suitable
      for process-based models because of its simplicity and because it does not
      require advance knowledge of the shape of the posterior distribution. Despite the
      suitability of Bayesian calibration, the technique has rarely been used in
      forestry research. We introduce the method, using the example of a typical forest
      model. Further, we show that reductions in parameter uncertainty, and thus in
      output uncertainty, can be effected by increasing the variety of data, increasing
      the accuracy of measurements and increasing the length of time series.

PMID- 15870059
TI  - A case study of forest management planning using a new heuristic algorithm.
AB  - We present an approach to generate and evaluate different silvicultural
      development paths and to optimize the development of a Norway spruce stand, using
      a long-term planning horizon. To generate a silvicultural path, the maximum stand
      density was applied. At each thinning event, three possible thinning intensities
      (10, 20, 30% of the stem number per ha) were randomly chosen. A search algorithm
      known as modified Accelerated Simulated Annealing (mASA) was used to estimate the
      optimum combination of stand paths for a given forest as a whole. Production and
      economic management objectives were considered and then compared. The economic
      criterion was the Expected Stand Value (ESV) with a 4% discount rate. The
      generated data set of 38 Norway spruce stands (comprising a total of 123.8 ha)
      was used in the case study. The result with the best combination of paths was
      presented in a digitized forest map. Forest management simulation was performed
      using a specially developed computer program, for a planning horizon of 20 years.
      The mASA proved to be an effective search method for identifying optimum paths.

PMID- 15870060
TI  - Evaluating the accuracy and generality of a hybrid patch model.
AB  - Forest patch models have been used extensively to simulate vegetation development
      under current and changing environmental conditions. However, their physiological
      foundation is subject to criticism and recent validation experiments against long
      term growth and yield data have shown major deficiencies in reproducing observed
      growth patterns of mixed-species forests. Here we describe the modified forest
      patch model PICUS Version 1.3, a model variant that couples the structurally
      detailed three-dimensional patch model PICUS Version 1.2 and the physiologically
      based stand-level production module of the 3-PG (Physiological Principles in
      Predicting Growth) model. The approach attempts to combine the ability of PICUS
      v1.2 to simulate forest dynamics on time scales relevant to forest succession
      with a simplified but successful production model based on the concept of
      radiation-use efficiency. We evaluated the hybrid model in a series of simulation
      experiments. Results indicated a realistic response to a climate sensitivity
      experiment: the response to environmental gradients was well captured both in
      terms of productivity on time scales of a rotation length and of forest
      succession over several hundreds of years. Testing against independent long- term
      growth and yield data revealed good correspondence between observed and predicted
      values of volume production and stand structure. Further model development should
      include a dynamic soil component to consider effects of nutrient cycling.

PMID- 15870061
TI  - A modeling analysis of the interaction between forest age and forest
      responsiveness to increasing CO2 concentration.
AB  - Typically, forests have rotations of 10-200 years. On that time scale,
      anthropogenic increases in atmospheric carbon dioxide concentration ([CO2]) and
      the associated changes in climate are expected to be substantial. These changes
      will, therefore, almost certainly affect the growth of presently established
      forest stands. Most studies on the effects of increasing [CO2] on tree growth
      have been made with young plants. However, the growth of trees within a forest
      stand varies with age. As a consequence, it is difficult to infer from the
      available experimental data how rising [CO2] will affect forest productivity over
      a full rotation. In this study, various mechanisms that may account for the
      slowing of forest growth with age were introduced into the forest growth model
      CenW, to assess how these processes affect the modeled growth response to
      increasing [CO2]. Inclusion of allocation shifts with tree height, individual
      tree mortality, changing respiration load and nutrient dynamics or age-based
      reductions in photosynthetic capacity had only small effects on the response to
      increasing [CO2]. However, when photosynthesis of mature trees was decreased as a
      function of size, then the growth response to increasing [CO2] was reduced
      because, at the same age, trees were larger in elevated than in ambient [CO2]. No
      simple and generally valid interactions between increasing [CO2] and forest age
      were identified because of the large number of interacting processes, all of
      which are incompletely understood. Important age x climate change interactions on
      productivity must occur in real forests and need to be considered to understand
      likely future trends. However, these interactions are complex and difficult to
      test. It is therefore not yet possible to predict with confidence the
      modification of the CO2 response by forest age.

PMID- 15870062
TI  - Effect of glaucoma on the retinal glutamate/glutamine cycle activity.
AB  - Glutamate-induced excitotoxicity has been proposed to mediate the death of
      retinal ganglion cells in glaucoma. The metabolic dependence of glutamatergic
      neurons upon glia via the glutamate/glutamine cycle to provide the precursor for
      neurotransmitter glutamate is well established. Thus, the aim of the present work
      was to study the retinal glutamate/glutamine activity in eyes with hypertension
      induced by intracameral injections of hyaluronic acid (HA). For this purpose,
      weekly injections of HA were performed unilaterally in the rat anterior chamber,
      whereas the contralateral eye was injected with saline solution. At 3 or 10 weeks
      of treatment, glutamate and glutamine uptake and release were assessed using [3H]
      glutamate and [3H]-glutamine as radioligands, respectively. In addition,
      glutamine synthetase activity was assessed by a spectrophotometric assay, whereas
      glutaminase activity was measured through the conversion of [3H]-glutamine to
      [3H]-glutamate. At 3 weeks of treatment with HA, a significant decrease (P<0.01)
      in glutamate uptake and glutamine synthetase activity was observed. Glutamine
      uptake and release, as well as glutaminase activity, were significantly increased
      (P<0.01) in eyes injected with HA for 3 weeks compared with vehicle-injected
      eyes, whereas [3H]-glutamate release did not change in hypertensive eyes. Only
      the changes in glutamine synthetase activity persisted at 10 weeks of treatment
      with HA. These results indicate a significant alteration in the retinal
      glutamate/glutamine cycle activity in hypertensive eyes. Since these changes
      preceded both functional and histological alterations induced by ocular
      hypertension, these results support the involvement of glutamate in glaucomatous
      neuropathy.

PMID- 15870063
TI  - Identification and structural determination of the M(3) muscarinic acetylcholine
      receptor basolateral sorting signal.
AB  - Muscarinic acetylcholine receptors comprise a family of G-protein-coupled
      receptors that display differential localization in polarized epithelial cells.
      We identify a seven-residue sequence, Ala(275)-Val(281), in the third
      intracellular loop of the M(3) muscarinic receptor that mediates dominant,
      position-independent basolateral targeting in Madin-Darby canine kidney cells.
      Mutational analyses identify Glu(276), Phe(280), and Val(281) as critical
      residues within this sorting motif. Phe(280) and Val(281) comprise a novel
      dihydrophobic sorting signal as mutations of either residue singly or together
      with leucine do not disrupt basolateral targeting. Conversely, Glu(276) is
      required and cannot be substituted with alanine or aspartic acid. A 19-amino acid
      peptide representing the M(3) sorting signal and surrounding sequence was
      analyzed via two-dimensional nuclear magnetic resonance spectroscopy. Solution
      structures show that Glu(276) resides in a type IV beta-turn and the
      dihydrophobic sequence Phe(280)Val(281) adopts either a type I or IV beta-turn.

PMID- 15870064
TI  - Pronounced conformational changes following agonist activation of the M(3)
      muscarinic acetylcholine receptor.
AB  - The conformational changes that convert G protein-coupled receptors (GPCRs)
      activated by diffusible ligands from their resting into their active states are
      not well understood at present. To address this issue, we used the M(3)
      muscarinic acetylcholine receptor, a prototypical class A GPCR, as a model
      system, employing a recently developed disulfide cross-linking strategy that
      allows the formation of disulfide bonds using Cys-substituted mutant M(3)
      muscarinic receptors present in their native membrane environment. In the present
      study, we generated and analyzed 30 double Cys mutant M(3) receptors, all of
      which contained one Cys substitution within the C-terminal portion of
      transmembrane domain (TM) VII (Val-541 to Ser-546) and another one within the C
      terminal segment of TM I (Val-88 to Phe-92). Following their transient expression
      in COS-7 cells, all mutant receptors were initially characterized in radioligand
      binding and second messenger assays (carbachol-induced stimulation of
      phosphatidylinositol hydrolysis). This analysis showed that all 30 double Cys
      mutant M(3) receptors were able to bind muscarinic ligands with high affinity and
      retained the ability to stimulate G proteins with high efficacy. In situ
      disulfide cross-linking experiments revealed that the muscarinic agonist,
      carbachol, promoted the formation of cross-links between specific Cys pairs. The
      observed pattern of disulfide cross-links, together with receptor modeling
      studies, strongly suggested that M(3) receptor activation induces a major
      rotational movement of the C-terminal portion of TM VII and increases the
      proximity of the cytoplasmic ends of TM I and VII. These findings should be of
      relevance for other family A GPCRs.

PMID- 15870065
TI  - Cellular quality control screening to identify amino acid pairs for substituting
      the disulfide bonds in immunoglobulin fold domains.
AB  - We are interested in determining which amino acid pairs can be substituted for
      the disulfide (S-S) bonds in proteins without disrupting their native structures
      under physiological conditions. In this study, we focused on the intradomain S-S
      bonds in Ig fold domains and aimed to determine a simple rule for replacement of
      their S-S bonds. The cysteines of four different Ig fold domains were mutated
      randomly, and the amino acid pairs substituted for the S-S bonds were screened by
      the method utilizing a cellular quality control system. Among the 36 selected
      mutants, 31 were natively folded without S-S bonds, as judged from the
      cooperativity of thermal unfolding. In addition, the selected mutant llama heavy
      chain antibodies retained antigen-binding affinity. At least two of the pairs
      Ala:Ala, Ala:Val, Val: Ala, and Val:Val were found in the selected mutants for
      all four different Ig fold domains, and they were stably folded at 30 degrees C.
      This suggests that examination of these four pairs could be enough to obtain
      natively folded Ig fold domains without S-S bonds.

PMID- 15870066
TI  - Cellular retinol-binding protein type III is needed for retinoid incorporation
      into milk.
AB  - The physiologic role(s) of cellular retinol-binding protein (CRBP)-III, an
      intracellular retinol-binding protein that is expressed solely in heart, muscle,
      adipose, and mammary tissue, remains to be elucidated. To address this, we have
      generated and characterized CRBP-III-deficient (CRBP-III(-/-)) mice. Mice that
      lack CRBP-III were viable and healthy but displayed a marked impairment in
      retinoid incorporation into milk. Milk obtained from CRBP-III(-/-) dams contains
      significantly less retinyl ester, especially retinyl palmitate, than milk
      obtained from wild type dams. We demonstrated that retinol bound to CRBP-III is
      an excellent substrate for lecithin-retinol acyltransferase, the enzyme
      responsible for catalyzing retinyl ester formation from retinol. Our data
      indicated that the diminished milk retinyl ester levels arise from impaired
      utilization of retinol by lecithin-retinol acyltransferase in CRBP-III(-/-) mice.
      Interestingly, CRBP-I and CRBP-III each appeared to compensate for the absence of
      the other, specifically in mammary tissue, adipose tissue, muscle, and heart. For
      CRBP-III(-/-) mice, CRBP-I protein levels were markedly elevated in adipose
      tissue and mammary gland. In addition, in CRBP-I(-/-) mice, CRBP-III protein
      levels were elevated in tissues that normally express CRBP-III but were not
      elevated in other tissues that do not normally express CRBP-III. Our data
      suggested that CRBP-I and CRBP-III share some physiologic actions within tissues
      and that each can compensate for the absence of the other to help maintain normal
      retinoid homeostasis. However, under conditions of high demand for retinoid, such
      as those experienced during lactation, this compensation was incomplete.

PMID- 15870067
TI  - Yin Yang 1 cooperates with activator protein 2 to stimulate ERBB2 gene expression
      in mammary cancer cells.
AB  - Overexpression of the ERBB2 oncogene is observed in about 30% of breast cancers
      and is generally correlated with a poor prognosis. Previous results from our and
      other laboratories indicated that elevated transcriptional activity contributes
      significantly to the overexpression of ERBB2 mRNA in mammary adenocarcinoma cell
      lines. Activator protein 2 (AP-2) transcription factors account for this
      overexpression through two recognition sequences located 215 and 500 bp upstream
      from the transcription start site. Furthermore, AP-2 transcription factors are
      highly expressed in cancer cell lines overexpressing ERBB2. In this report, we
      examined the cooperative effect of Yin Yang 1 (YY1) on AP-2-induced activation of
      ERBB2 promoter activity. We detected high levels of YY1 transcription factor in
      mammary cancer cell lines. Notably, we showed that YY1 enhances AP-2alpha
      transcriptional activation of the ERBB2 promoter through an AP-2 site both in
      HepG2 and in HCT116 cells, whereas a carboxyl-terminal-truncated form of YY1
      cannot. Moreover, we demonstrated the interaction between endogenous AP-2 and YY1
      factors in the BT-474 mammary adenocarcinoma cell line. In addition, inhibition
      of endogenous YY1 protein by an antisense decreased the transcription of an AP-2
      responsive ERBB2 reporter plasmid in BT-474 breast cancer cells. Finally, we
      detected in vivo AP-2 and YY1 occupancy of the ERBB2 proximal promoter in
      chromatin immunoprecipitation assays. Our data thus provide evidence that YY1
      cooperates with AP-2 to stimulate ERBB2 promoter activity through the AP-2
      binding sites.

PMID- 15870068
TI  - Characterization of the interaction between interleukin-13 and interleukin-13
      receptors.
AB  - Interleukin-13 (IL-13) possesses two types of receptor: the heterodimer, composed
      of the IL-13Ralpha1 chain (IL-13Ralpha1) and the IL-4Ralpha chain (IL-4Ralpha),
      transducing the IL-13 signals; and the IL-13Ralpha2 chain (IL-13Ralpha2), acting
      as a nonsignaling "decoy" receptor. Extracellular portions of both IL-13Ralpha1
      and IL-13Ralpha2 are composed of three fibronectin type III domains, D1, D2, and
      D3, of which the last two comprise the cytokine receptor homology modules (CRHs),
      a common structure of the class I cytokine receptor superfamily. Thus far, there
      has been no information about the critical amino acids of the CRHs or the role of
      the D1 domains of IL-13Ralpha1 and IL-13Ralpha2 in binding to IL-13. In this
      study, we first built the homology modeling of the IL-13.hIL-13 receptor
      complexes and then predicted the amino acids involved in binding to IL-13. By
      incorporating mutations into these amino acids, we identified Tyr-207, Asp-271,
      Tyr-315, and Asp-318 in the CRH of human IL-13Ralpha2, and Leu-319 and Tyr-321 in
      the CRH of human IL-13Ralpha1, as critical residues for binding to IL-13. Tyr-315
      in IL-13Ralpha2 and Leu-319 in IL-13Ralpha1 are positionally conserved
      hydrophobic amino acid residues. Furthermore, by using D1 domain-deleted mutants,
      we found that the D1 domain is needed for the expression of IL-13Ralpha2, but not
      IL-13Ralpha1, and that the D1 domain of IL-13Ralpha1 is important for binding to
      IL-13, but not to IL-4. These results provide the basis for a precise
      understanding of the interaction between IL-13 and its receptors.

PMID- 15870069
TI  - High resolution reaction intermediates of rabbit muscle fructose-1,6-bisphosphate
      aldolase: substrate cleavage and induced fit.
AB  - Crystal structures were determined to 1.8 A resolution of the glycolytic enzyme
      fructose-1,6-bis(phosphate) aldolase trapped in complex with its substrate and a
      competitive inhibitor, mannitol-1,6-bis(phosphate). The enzyme substrate complex
      corresponded to the postulated Schiff base intermediate and has reaction geometry
      consistent with incipient C3-C4 bond cleavage catalyzed Glu-187, which is
      adjacent by to the Schiff base forming Lys-229. Atom arrangement about the
      cleaved bond in the reaction intermediate mimics a pericyclic transition state
      occurring in nonenzymatic aldol condensations. Lys-146 hydrogen-bonds the
      substrate C4 hydroxyl and assists substrate cleavage by stabilizing the
      developing negative charge on the C4 hydroxyl during proton abstraction. Mannitol
      1,6-bis(phosphate) forms a noncovalent complex in the active site whose binding
      geometry mimics the covalent carbinolamine precursor. Glu-187 hydrogen-bonds the
      C2 hydroxyl of the inhibitor in the enzyme complex, substantiating a proton
      transfer role by Glu-187 in catalyzing the conversion of the carbinolamine
      intermediate to Schiff base. Modeling of the acyclic substrate configuration into
      the active site shows Glu-187, in acid form, hydrogen-bonding both substrate C2
      carbonyl and C4 hydroxyl, thereby aligning the substrate ketose for nucleophilic
      attack by Lys-229. The multifunctional role of Glu-187 epitomizes a canonical
      mechanistic feature conserved in Schiff base-forming aldolases catalyzing
      carbohydrate metabolism. Trapping of tagatose-1,6-bis(phosphate), a
      diastereoisomer of fructose 1,6-bis(phosphate), displayed stereospecific
      discrimination and reduced ketohexose binding specificity. Each ligand induces
      homologous conformational changes in two adjacent alpha-helical regions that
      promote phosphate binding in the active site.

PMID- 15870070
TI  - The expression of endothelial nitric-oxide synthase is controlled by a cell
      specific histone code.
AB  - Expression of endothelial nitric-oxide synthase (eNOS) mRNA is highly restricted
      to the endothelial cell layer of medium to large sized arterial blood vessels.
      Here we assessed the chromatin environment of the eNOS gene in expressing and
      nonexpressing cell types. Within endothelial cells, but not a variety of
      nonendothelial cells, the nucleosomes that encompassed the eNOS core promoter and
      proximal downstream coding regions were highly enriched in acetylated histones H3
      and H4 and methylated lysine 4 of histone H3. This differentially modified
      chromatin domain was selectively associated with functionally competent RNA
      polymerase II complexes. Endothelial cells were particularly enriched in
      acetylated histone H3 lysine 9, histone H4 lysine 12, and di- and tri-methylated
      lysine 4 of histone H3 at the core promoter. Histone modifications at this
      region, which we have previously demonstrated to exhibit cell-specific DNA
      methylation, were functionally relevant to eNOS expression. Inhibition of histone
      deacetylase activity by trichostatin A increased acetylation of histones H3 and
      H4 at the eNOS proximal promoter in nonexpressing cell types and led to increased
      steady-state eNOS mRNA transcript levels. H3 lysine 4 methylation was also
      essential for eNOS expression, since treatment of endothelial cells with
      methylthioadenosine, a known lysine 4 methylation inhibitor, decreased eNOS RNA
      levels, H3 lysine 4 methylation, and RNA polymerase II loading at the eNOS
      proximal promoter. Importantly, methylthioadenosine also prevented the
      trichostatin A-mediated increase in eNOS mRNA transcript levels in nonendothelial
      cells. Taken together, these findings provide strong evidence that the
      endothelial cell-specific expression of eNOS is controlled by cell-specific
      histone modifications.

PMID- 15870071
TI  - Fibroblast growth factor-1 induces heme oxygenase-1 via nuclear factor erythroid
      2-related factor 2 (Nrf2) in spinal cord astrocytes: consequences for motor
      neuron survival.
AB  - Fibroblast growth factor-1 (FGF-1) is highly expressed in motor neurons and can
      be released in response to sublethal cell injury. Because FGF-1 potently
      activates astroglia and exerts a direct neuroprotection after spinal cord injury
      or axotomy, we examined whether it regulated the expression of inducible and
      cytoprotective heme oxygenase-1 (HO-1) enzyme in astrocytes. FGF-1 induced the
      expression of HO-1 in cultured rat spinal cord astrocytes, which was dependent on
      FGF receptor activation and prevented by cycloheximide. FGF-1 also induced Nrf2
      mRNA and protein levels and prompted its nuclear translocation. HO-1 induction
      was abolished by transfection of astrocytes with a dominant-negative mutant Nrf2,
      indicating that FGF-1 regulates HO-1 expression through Nrf2. FGF-1 also modified
      the expression of other antioxidant genes regulated by Nrf2. Both Nrf2 and HO-1
      levels were increased and co-localized with reactive astrocytes in the
      degenerating lumbar spinal cord of rats expressing the amyotrophic lateral
      sclerosis-linked SOD1 G93A mutation. Overexpression of Nrf2 in astrocytes
      increased survival of co-cultured embryonic motor neurons and prevented motor
      neuron apoptosis mediated by nerve growth factor through p75 neurotrophin
      receptor. Taken together, these results emphasize the key role of astrocytes in
      determining motor neuron fate in amyotrophic lateral sclerosis.

PMID- 15870072
TI  - A peptide triggers allostery in tet repressor by binding to a unique site.
AB  - Regulatory proteins often communicate with each other to manage various cellular
      processes. Such interactions mostly rely on the recognition of small peptide
      motifs. The activity of other regulatory proteins depends on small molecular
      weight effectors and allostery. We demonstrate the in vivo regulation of the
      tetracycline-dependent Tet repressor by an oligopeptide fused to the N or C
      terminus of thioredoxin A. The binding site of the peptide overlaps but is not
      identical with the tetracycline binding site. Several TetR mutants that are non
      inducible by tetracycline also respond to the peptide. This demonstrates for the
      first time the conversion of a small molecular weight effector-dependent
      regulator to a protein-protein contact-dependent potential member of designed
      signaling chains.

PMID- 15870073
TI  - Phosphorylation-independent regulation of metabotropic glutamate receptor 1
      signaling requires g protein-coupled receptor kinase 2 binding to the second
      intracellular loop.
AB  - Metabotropic glutamate receptors (mGluRs) are members of a unique class of G
      protein-coupled receptors (class III) that include the calcium-sensing and gamma
      aminobutyric acid type B receptors. The activity of mGluRs is regulated by second
      messenger-dependent protein kinases and G protein-coupled receptor kinases
      (GRKs). The attenuation of both mGluR1a and mGluR1b signaling by GRK2 is
      phosphorylation- and beta-arrestin-independent and requires the concomitant
      association of GRK2 with both the receptor and Galpha(q/11). G protein
      interactions are mediated, in part, by the mGluR1 intracellular second loop, but
      the domains required for GRK2 binding are unknown. In the present study, we
      showed that GRK2 binds to the second intracellular loop of mGluR1a and mGluR1b
      and also to the mGluR1a carboxyl-terminal tail. Alanine scanning mutagenesis
      revealed a discrete domain within loop 2 that contributes to GRK2 binding, and
      the mutation of either lysine 691 or 692 to an alanine within this domain
      resulted in a loss of GRK2 binding to both mGluR1a and mGluR1b. Mutation of
      either Lys(691) or Lys(692) prevented GRK2-mediated attenuation of mGluR1b
      signaling, whereas the mutation of only Lys(692) prevented GRK2-mediated
      inhibition of mGluR1a signaling. Thus, the mGluR1a carboxyl-terminal tail may
      also be involved in regulating the signaling of the mGluR1a splice variant. Taken
      together, our findings indicated that kinase binding to an mGluR1 domain involved
      in G protein-coupling is essential for the phosphorylation-independent
      attenuation of signaling by GRK2.

PMID- 15870074
TI  - Pituitary adenylyl cyclase-activating polypeptide 38 reduces astroglial
      proliferation by inhibiting the GTPase RhoA.
AB  - Pituitary adenylyl cyclase-activating polypeptide 38 (PACAP38) plays an important
      role in the proliferation and differentiation of neural cells. In the present
      study, we have investigated how PACAP38 inhibits the proliferation of cultured
      neocortical astroglial cells. When applied to synchronized cells during the G(1)
      phase of the cell cycle, PACAP38 diminished the subsequent nuclear uptake of
      bromodeoxyuridine. When applied for 2 days, it reduced the cell number. PACAP38
      did not exert its antiproliferative effect by activating protein kinase A. It
      also did not reduce the activity of mitogen-activated protein kinases essential
      for G(1) phase progression. Instead, PACAP38 acted on a member of the Rho family
      of small GTPases. It reduced the activity of RhoA as was shown with a Rhotekin
      pull-down assay. The decrease in endogenous RhoA activity induced by treatment of
      the cells with C3 exotoxin or by expression of dominant negative RhoA also
      reduced the nuclear uptake of bromodeoxyuridine. In contrast, expression of
      constitutively active RhoA prevented the effect of PACAP38. Our data show a novel
      signal transduction pathway by which the neuropeptide influences cell
      proliferation.

PMID- 15870076
TI  - Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear
      factor-4{alpha}.
AB  - Hepatocyte nuclear factor-4alpha (HNF-4alpha) activity is modulated by natural
      and xenobiotic fatty acid and fatty acyl-CoA ligands as a function of their chain
      length, unsaturation, and substitutions. The acyl-CoA site of HNF-4alpha is
      reported here to consist of the E-F domain, to bind long-chain acyl-CoAs but not
      the respective free acids, and to catalyze the hydrolysis of bound fatty acyl
      CoAs. The free acid pocket, previously reported in the x-ray structure of HNF
      4alpha E-domain, entraps fatty acids but excludes acyl-CoAs. The acyl-CoA and
      free acid sites are distinctive and noncongruent. Free fatty acid products of HNF
      4alpha thioesterase may exchange with free acids entrapped in the fatty acid
      pocket of HNF-4alpha. Cross-talk between the acyl-CoA and free fatty acid binding
      sites is abrogated by high affinity, nonhydrolyzable acyl-CoA ligands of HNF
      4alpha that inhibit its thioesterase activity. Hence, HNF-4alpha transcriptional
      activity is controlled by its two interrelated acyl ligands and two binding sites
      interphased in tandem by the thioesterase activity. The acyl-CoA/free-acid and
      receptor/enzyme duality of HNF-4alpha extends the paradigm of nuclear receptors.

PMID- 15870075
TI  - Sertoli-germ cell anchoring junction dynamics in the testis are regulated by an
      interplay of lipid and protein kinases.
AB  - When Sertoli and germ cells were co-cultured in vitro in serum-free chemically
      defined medium, functional anchoring junctions such as cell-cell intermediate
      filament-based desmosome-like junctions and cell-cell actin-based adherens
      junctions (e.g. ectoplasmic specialization (ES)) were formed within 1-2 days.
      This event was marked by the induction of several protein kinases such as
      phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (PKB; also
      known as Akt), p21-activated kinase-2 (PAK-2), and their downstream effector
      (ERK) as well as an increase in PKB intrinsic activity. PI3K, phospho (p)-PKB,
      and PAK were co-localized to the site of apical ES in the seminiferous epithelium
      of the rat testis in immunohistochemistry studies. Furthermore, PI3K also co
      localized with p-PKB to the same site in the epithelium as determined by
      fluorescence microscopy, consistent with their localization at the ES. These
      kinases were shown to associate with ES-associated proteins such as beta1
      integrin, phosphorylated focal adhesion kinase, and c-Src by co
      immunoprecipitation, suggesting that the integrin.laminin protein complex at the
      apical ES likely utilizes these protein kinases as regulatory proteins to
      modulate Sertoli-germ cell adherens junction dynamics via the ERK signaling
      pathway. To validate this hypothesis further, an in vivo model using AF-2364 (1
      (2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide) to perturb Sertoli-germ cell
      anchoring junction function, inducing germ cell loss from the epithelium in adult
      rats, was used in conjunction with specific inhibitors. Interestingly, the event
      of germ cell loss induced by AF-2364 in vivo was also associated with induction
      of PI3K, p-PKB, PAK-2, and p-ERK as well as a surge in intrinsic PKB activity.
      Perhaps the most important of all, pretreatment of rats with wortmannin (a PI3K
      inhibitor) or anti-beta1-integrin antibody via intratesticular injection indeed
      delayed AF-2364-induced spermatid loss from the epithelium. In summary, these
      results illustrate that Sertoli-germ cell anchoring junction dynamics in the
      testis are regulated, at least in part, via the beta1-integrin/PI3K/PKB/ERK
      signaling pathway.

PMID- 15870078
TI  - The broadly selective human Na+/nucleoside cotransporter (hCNT3) exhibits novel
      cation-coupled nucleoside transport characteristics.
AB  - The concentrative nucleoside transporter (CNT) protein family in humans is
      represented by three members, hCNT1, hCNT2, and hCNT3. hCNT3, a Na+/nucleoside
      symporter, transports a broad range of physiological purine and pyrimidine
      nucleosides as well as anticancer and antiviral nucleoside drugs, and belongs to
      a different CNT subfamily than hCNT1/2. H+-dependent Escherichia coli NupC and
      Candida albicans CaCNT are also CNT family members. The present study utilized
      heterologous expression in Xenopus oocytes to investigate the specificity,
      mechanism, energetics, and structural basis of hCNT3 cation coupling. hCNT3
      exhibited uniquely broad cation interactions with Na+, H+, and Li+ not shared by
      Na+-coupled hCNT1/2 or H+-coupled NupC/CaCNT. Na+ and H+ activated hCNT3 through
      mechanisms to increase nucleoside apparent binding affinity. Direct and indirect
      methods demonstrated cation/nucleoside coupling stoichiometries of 2:1 in the
      presence of Na+ and both Na+ plus H+, but only 1:1 in the presence of H+ alone,
      suggesting that hCNT3 possesses two Na+-binding sites, only one of which is
      shared by H+. The H+-coupled hCNT3 did not transport guanosine or 3'-azido-3'
      deoxythymidine and 2',3'-dideoxycytidine, demonstrating that Na+- and H+-bound
      versions of hCNT3 have significantly different conformations of the nucleoside
      binding pocket and/or translocation channel. Chimeric studies between hCNT1 and
      hCNT3 located hCNT3-specific cation interactions to the C-terminal half of hCNT3,
      setting the stage for site-directed mutagenesis experiments to identify the
      residues involved.

PMID- 15870077
TI  - Jumonji regulates cardiomyocyte proliferation via interaction with retinoblastoma
      protein.
AB  - Jumonji (JMJ) can function as a transcriptional repressor and plays critical
      roles in embryonic development including heart development in mice. Although JMJ
      has been suggested to play a role in cell growth, the molecular mechanisms have
      not been resolved. The present data demonstrate that JMJ interacts with the
      retinoblastoma protein (Rb), one of the master regulatory genes of cell cycle.
      JMJ potentiates the repression function of Rb on E2F activities, leading to
      reduced cell cycle progression. The transcriptional repression domain of JMJ is
      critical for the interaction with Rb as well as repression of cell cycle. The
      physiological relevance of the association between Rb and JMJ was assessed in
      cardiomyocytes. Primary cardiomyocytes cultured from homozygous jmj knock-out
      mouse embryos (jmj mutants) show increased cell mitosis in a cardiomyocyte
      specific manner. Reporter gene analyses demonstrate that promoter activities of
      cyclin D1, cyclin D2, and Cdc2 are up-regulated in jmj mutant cardiomyocytes.
      These data suggest that JMJ down-regulates the cell growth via interaction with
      Rb, which would provide important insights into the cardiac defects observed in
      jmj mutant mice.

PMID- 15870079
TI  - A vertebrate-type ferredoxin domain in the Na+-translocating NADH dehydrogenase
      from Vibrio cholerae.
AB  - The Na(+)-translocating NADH:quinone oxidoreductase from Vibrio cholerae contains
      a single Fe-S cluster localized in subunit NqrF. Here we study the electronic
      properties of the Fe-S center in a truncated version of the NqrF subunit
      comprising only its ferredoxin-like Fe-S domain. Mossbauer spectroscopy of the Fe
      S domain in the oxidized state is consistent with a binuclear Fe-S cluster with
      tetrahedral sulfur coordination by the cysteine residues Cys(70), Cys(76),
      Cys(79), and Cys(111). Important sequence motifs surrounding these cysteines are
      conserved in the Fe-S domain and in vertebrate-type ferredoxins. The magnetic
      circular dichroism spectra of the photochemically reduced Fe-S domain exhibit a
      striking similarity to the magnetic circular dichroism spectra of vertebrate-type
      ferredoxins required for the in vivo assembly of iron-sulfur clusters. This study
      reveals a novel function for vertebrate-type [2Fe-2S] clusters as redox cofactors
      in respiratory dehydrogenases.

PMID- 15870080
TI  - Cleavage site selection within a folded substrate by the ATP-dependent lon
      protease.
AB  - Mechanistic studies of ATP-dependent proteolysis demonstrate that substrate
      unfolding is a prerequisite for processive peptide bond hydrolysis. We show that
      mitochondrial Lon also degrades folded proteins and initiates substrate cleavage
      non-processively. Two mitochondrial substrates with known or homology-derived
      three-dimensional structures were used: the mitochondrial processing peptidase
      alpha-subunit (MPPalpha) and the steroidogenic acute regulatory protein (StAR).
      Peptides generated during a time course of Lon-mediated proteolysis were
      identified and mapped within the primary, secondary, and tertiary structure of
      the substrate. Initiating cleavages occurred preferentially between hydrophobic
      amino acids located within highly charged environments at the surface of the
      folded protein. Subsequent cleavages proceeded sequentially along the primary
      polypeptide sequence. We propose that Lon recognizes specific surface
      determinants or folds, initiates proteolysis at solvent-accessible sites, and
      generates unfolded polypeptides that are then processively degraded.

PMID- 15870081
TI  - Diacylglycerol kinase alpha regulates the secretion of lethal exosomes bearing
      Fas ligand during activation-induced cell death of T lymphocytes.
AB  - Fas ligand (FasL) mediates both apoptotic and inflammatory responses in the
      immune system. FasL function critically depends on the different forms of FasL;
      soluble Fas ligand lacking the transmembrane and cytoplasmic domains is a poor
      mediator of apoptosis, whereas full-length, membrane-associated FasL (mFasL) is
      pro-apoptotic. mFasL can be released from T lymphocytes, via the secretion of
      mFasL-bearing exosomes. mFasL in exosomes retains its activity in triggering Fas
      dependent apoptosis, providing an alternative mechanism of cell death that does
      not necessarily imply cell-to-cell contact. Diacylglycerol kinase alpha
      (DGKalpha), a diacylglycerol (DAG)-consuming enzyme, is involved in the
      attenuation of DAG-derived responses initiated at the plasma membrane that lead
      to T lymphocyte activation. Here we studied the role of DGKalpha on activation
      induced cell death on a T cell line and primary T lymphoblasts. The inhibition of
      DGKalpha increases the secretion of lethal exosomes bearing mFas ligand and
      subsequent apoptosis. On the contrary, the overactivation of the DGKalpha pathway
      inhibits exosome secretion and subsequent apoptosis. DGKalpha was found
      associated with the trans-Golgi network and late endosomal compartments. Our
      results support the hypothesis that the DGKalpha effect on apoptosis occurs via
      the regulation of the release of lethal exosomes by the exocytic pathway, and
      point out that the spatial orchestration of the different pools of DAG (plasma
      membrane and Golgi membranes) by DGKalpha is crucial for the control of cell
      activation and also for the regulation of the secretion of lethal exosomes, which
      in turn controls cell death.

PMID- 15870082
TI  - Relevance of EGFR expression in colorectal cancer.

PMID- 15870083
TI  - Cyclooxygenase inhibitors may be more effective in hormone-dependent endometrial
      cancers: interaction between cyclooxygenase and aromatase.

PMID- 15870084
TI  - Neoadjuvant treatment of unresectable colorectal liver metastases: correlation
      between tumour response and resection rates.
AB  - BACKGROUND: Long-term survival is reported in patients with liver metastases of
      colorectal cancer. Recently, an increased number of reports on liver resection
      following neoadjuvant chemotherapy in patients with initially unresectable liver
      metastases has been published. METHODS: We analysed all published or presented
      trials and retrospective studies that report the rate of objective response and
      the rate of resection of initially unresectable metastases to correlate objective
      response and the rate of resection of metastases. RESULTS: In studies that
      enrolled patients with metastases confined to the liver, 24-54% of patients were
      resected following chemotherapy, compared to 1-26% of patients in trials that
      included non-selected patients with metastatic colorectal cancer. A strong
      correlation was found between response rates and the resection rate in studies
      with patients with isolated liver metastases (r = 0.96, P=0.002). Likewise, in
      studies with non-selected patients, the resection rate of metastases also was
      associated with the objective response rate (r = 0.74, P <0.001). CONCLUSIONS:
      Patient selection and efficacy of pre-operative chemotherapy are both strong
      predictors for resectability of liver metastases. Resectability is a novel
      endpoint focusing on the curative potential of treatment compared with classical
      endpoints of response or progression-free survival that are important if
      palliation is the aim. Therefore, patients with potentially resectable liver
      metastases should be investigated in special trials and interdisciplinary teams.

PMID- 15870085
TI  - Chemotherapy-induced amenorrhea: influence on disease-free survival and overall
      survival in receptor-positive premenopausal early breast cancer patients.
AB  - BACKGROUND: The aim of this study was to evaluate the influence of early
      chemotherapy-induced amenorrhea (CIA) on disease-free survival and overall
      survival in premenopausal patients with receptor-positive early breast cancer
      treated with adjuvant chemotherapy without any hormonotherapy. PATIENTS AND
      METHODS: Retrospectively, we reviewed data from 130 premenopausal patients with
      localized hormone-sensitive breast cancer. These patients were treated between
      1985 and 1995 at the same institution. They all underwent a loco-regional
      treatment and adjuvant chemotherapy. Early CIA was defined as an amenorrhea
      arising during the first year following the beginning of chemotherapy. Predictors
      of early CIA were examined. The survival analyses were done using the Kaplan
      Meier method and Cox analysis. RESULTS: Median follow-up was 9 years. Mean age
      was 42.9 +/- 5 years. Ninety-two per cent of patients had histologically-proven
      positive axillary nodes. Adjuvant chemotherapy contained no anthracycline in 63%.
      Early CIA occurred during or after adjuvant chemotherapy in 57% of the patients.
      It was definitive in 91%. In our study, age was the only CIA predictor in
      univariate analysis. Women who experienced early CIA tend to have a longer
      disease-free survival, but the difference was not significant. This trend was
      lost in multivariate analysis, most probably due to the small sample size. The
      overall survival was not different. CONCLUSION: Although not statistically
      significant, our results on a very selected population of patients suggest that a
      chemotherapy-induced amenorrhea might have its own therapeutic effect besides the
      cytotoxic action of chemotherapy.

PMID- 15870086
TI  - Antitumoral actions of the anti-obesity drug orlistat (XenicalTM) in breast
      cancer cells: blockade of cell cycle progression, promotion of apoptotic cell
      death and PEA3-mediated transcriptional repression of Her2/neu (erbB-2) oncogene.
AB  - BACKGROUND: Orlistat (Xenicaltrade mark), a US Food and Drug Administration (FDA)
      approved drug for bodyweight loss, has recently been demonstrated to exhibit
      antitumor properties towards prostate cancer cells by virtue of its ability to
      block the lipogenic activity of fatty acid synthase (FAS). FAS (oncogenic antigen
      519) is up-regulated in about 50% of breast cancers, is an indicator of poor
      prognosis, and has recently been functionally associated with the Her2/neu (erbB
      2) oncogene. MATERIALS AND METHODS: We assessed the antitumoral effects of
      orlistat against the human breast cancer cell line SK-Br3, an in vitro paradigm
      of FAS and Her2/neu overexpression in breast cancer. RESULTS: Cell cycle analyses
      revealed that micromolar concentrations of orlistat induced, in a time- and dose
      dependent manner, significant changes in the distribution of cell populations
      including a complete loss of G2-M phase, S-phase accumulation and a concomitant
      increase in the emerging sub-G1 (apoptotic) cells. Poly (ADP-ribose) polymerase
      (PARP) cleavage, an early event required for cells committed to apoptosis, was
      more predominant in orlistat-treated G1 phase cells. When we characterized
      signaling molecules participating in the cellular events following orlistat
      induced inhibition of FAS activity and preceded inhibition of breast cancer cell
      proliferation, a dramatic down-regulation of Her2/neu-coded p185(Her2/neu)
      oncoprotein was found in orlistat-treated SK-Br3 cells (>90% reduction).
      Interestingly, a significant accumulation of the DNA-binding protein PEA3, a
      member of the Ets transcription factor family that specifically targets a PEA3
      binding motif present on the Her2/neu gene promoter and down-regulates its
      activity, was observed in orlistat-treated SK-Br3 cells. When a Luciferase
      reporter gene driven by the Her2/neu promoter was transiently transfected in SK
      Br3 cells, orlistat exposure was found to dramatically repress the promoter
      activity of Her2/neu gene, whereas a Her2/neu promoter bearing a mutated binding
      DNA sequence was not subject to negative regulation by orlistat, thus
      demonstrating that the intact PEA3 binding site on the Her2/neu promoter is
      required for the orlistat-induced transcriptional repression of Her2/neu
      overexpression. RNA interference (RNAi)-mediated silencing of FAS gene expression
      similarly repressed Her2/neu gene expression in a PEA3-dependent manner, thus
      ruling out a role for non-FAS orlistat-mediated effects. When the combination of
      orlistat and the anti-Her2/neu antibody trastuzumab (Herceptintrade mark) in
      either concurrent (orlistat + trastuzumab) or sequential (orlistat -->
      trastuzumab; trastuzumab --> orlistat) schedules was tested for synergism,
      addition or antagonism using the combination index (CI) method of Chou-Talalay,
      co-exposure of orlistat and trastuzumab demonstrated strong synergistic effects
      (CI10-90 = 0.110-0.847), whereas sequential exposure to orlistat followed by
      trastuzumab (CI10-90 = 0.380-1.210) and trastuzumab followed by orlistat (CI10-90
      = 0.605-1.278) mainly showed additive or antagonistic interactions. Indeed,
      orlistat-induced FAS inhibition synergistically promoted apoptotic cell death
      when concurrently combined with trastuzumab as determined by an ELISA for histone
      associated DNA fragments. Importantly, the degree of FAS expression in a panel of
      human breast cancer cell lines was predictive of sensitivity to orlistat-induced
      anti-proliferative effects as determined by a MTT-based characterization of
      metabolically viable breast cancer cells. Moreover, hypersensitivity to orlistat
      induced cytotoxicity was observed in MCF-7 breast cancer cells engineered to
      overexpress Her2/neu (MCF-7/Her2-18 cells), which exhibit a significant up
      regulation of FAS expression and activity. CONCLUSIONS: These findings reveal
      that the development of more potent and/or bioavailable orlistat's variants
      targeting the lipogenic activity of FAS may open a novel therapeutic avenue for
      treating Her2/neu-overexpressing breast carcinomas.

PMID- 15870087
TI  - Reply to the Letter to the Editor on "Third generation aromatase inhibitors may
      prevent endometrial growth and reverse tamoxifen-induced uterine changes in
      postmenopausal breast cancer patients", by I. Cohen Ann Oncol 2005; 16: 1399.

PMID- 15870088
TI  - Clinical impact of whole-body FDG-PET for evaluation of response and therapeutic
      decision-making of primary lymphoma of bone.

PMID- 15870089
TI  - Comment on 'Cancer genetic counselling' by P. Mandich et al. (Ann Oncol 2005; 16:
      171).

PMID- 15870090
TI  - Neoadjuvant phase II multicentre study of new agents in patients with malignant
      glioma after minimal surgery. Report of a cohort of 187 patients treated with
      temozolomide.
AB  - BACKGROUND: The aim of this study was to assess the efficacy of new agents in
      patients with malignant glioma in a neoadjuvant setting not confounded by
      surgery. The first study of neoadjuvant temozolomide aimed to provide a benchmark
      for future evaluation of new treatments. PATIENTS AND METHODS: This was a
      multicentre phase II study of chemotherapy in patients with histologically
      verified glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA) who had
      undergone biopsy alone. Patients were planned to receive two cycles of
      temozolomide at 200 mg/m(2) orally daily for 5 days at a 28-day interval prior to
      radiotherapy. Response was assessed by two central observers on pre- and post
      chemotherapy enhanced scans using bi-dimensional criteria and as progression-free
      survival (PFS) at the time of second assessment prior to radiotherapy. Withdrawal
      from the study due to worsening clinical condition was, in the absence of second
      imaging, assessed as progressive disease. Survival and quality of life (QOL) were
      secondary endpoints. RESULTS: Between August 1999 and June 2002, 188 patients
      from 15 UK and two Italian centres were entered into the study and 187 were
      analysed. Overall, 162 patients were assessable for response; seven had partial
      and 25 had minimal response. The objective response rate was 20% [95% confidence
      interval (CI) 14-26%] and PFS prior to commencing radiotherapy was 64% (95% CI 57
      72%). The median survival was 10 months, and 1-year survival 41%. The median
      survival of responders was 16 months compared to 3 months in patients with
      progressive disease (P <0.001 on multivariate analysis). CONCLUSION: The phase II
      study design of primary chemotherapy in patients with malignant glioma following
      biopsy alone is feasible and provides as objective a method of assessment of
      efficacy as is currently available. The baseline data on temozolomide provide a
      benchmark for assessment of efficacy of other agents and combinations.

PMID- 15870091
TI  - Alcohol intake and the pattern of trauma in young adults and working aged people
      admitted after trauma.
AB  - AIMS: To investigate the relationship of different patterns of alcohol intake to
      various types of trauma. METHODS: We examined the associations of alcohol
      consumption in a series of 385 consecutive trauma admissions (278 men, 107 women,
      age range 16-49 years). Patients underwent clinical examinations, structured
      interviews on the amount and pattern of alcohol intake, and measurements of blood
      alcohol concentration (BAC). RESULTS: On admission, 51% of the patients had
      alcohol in their blood. Binge drinking was the predominant (78%) drinking pattern
      of alcohol intake. Assaults, falls and biking accidents were the most frequent
      causes of trauma. Dependent alcohol drinking and binge drinking were found to be
      significantly more common among patients with head trauma than in those with
      other types of trauma (77% vs 59%, OR=2.38; 95% CI 1.50 to 3.77). The OR for
      sustaining head injury increased sharply with increasing BAC: 1-99 mg/dl (1.24;
      95% CI 0.55-2.01), 100-149 mg/dl 1.64; 95% CI 0.71-3.77), 150-199 mg/dl (3.20;
      95% CI 1.57-6.53) and >199 mg/dl (9.23; 95% CI 4.79-17.79). CONCLUSIONS: Binge
      drinking is a major risk factor for head trauma among trauma patients. Assaults,
      falls and biking accidents are the commonest causes for such injuries. The
      relative risk for head injury markedly increases with increasing blood alcohol
      levels. Alcohol control measures should feature in policies aiming at the
      prevention of trauma-related morbidity and mortality.

PMID- 15870092
TI  - Effect of community nurse follow-up when treating alcohol dependence with
      acamprosate.
AB  - AIMS: To measure the effect of community nurse follow-up on abstinence and
      retention rates in the outpatient treatment of alcohol-dependent patients treated
      with acamprosate. METHODS: Recently detoxified alcohol-dependent patients were
      prescribed acamprosate for 26 weeks and randomized to either physician-only
      follow-up, or physician plus regular visits from a community nurse. Drinking
      behaviour in the next 26 weeks was assessed at monthly visits to non-blind
      clinicians. RESULTS: The cumulative abstinence duration proportion (CADP) was
      significantly longer in (P=0.03) the subjects who had received community nurse
      support (0.57) than in those who had not (0.39). This might, in part, be an
      artefact of the higher retention rate among those followed up by the nurse, in
      that, the method of calculating CADP allocates 100% days of drinking for the
      month before a failed attendance. Differences favouring nurse in the follow-up
      were seen for time to first drink, and clinical global impression. CONCLUSIONS:
      For recently detoxified alcohol-dependent patients treated with acamprosate,
      follow-up by a community nurse improves patient retention and probably also
      improves the 6-month drinking outcome.

PMID- 15870093
TI  - Effect of Hypericum perforatum CO2 extract on the motivational properties of
      ethanol in alcohol-preferring rats.
AB  - AIMS: Extracts of Hypericum perforatum (HPE) attenuate voluntary ethanol intake
      in different lines of alcohol-preferring rats. The present study evaluated the
      effect of the intragastric (IG) administration of a CO(2) Hypericum perforatum
      extract (HPCO(2)) on operant ethanol self-administration, as well as on voluntary
      ethanol intake, after a period of ethanol deprivation in genetically selected
      Marchigian Sardinian alcohol-preferring rats. METHODS: HPCO2 was administered by
      means of an indwelling IG catheter, 1 h before the tests. For the self
      administration experiments, the rats were trained to self-administer 10% (v/v)
      ethanol in 30-min daily sessions under a fixed ratio 1 schedule of reinforcement.
      HPCO2 was also tested on 0.2% w/v saccharin self-administration. For the ethanol
      deprivation experiments, rats that had a previous experience with voluntary
      ethanol drinking were deprived of ethanol for 9 days, whereas water and food were
      freely available; HPCO2 was given by IG injection 1 h before the ethanol re
      presentation. RESULTS: HPCO2 in doses of 31 or 125 mg/kg but not 7 mg/kg,
      significantly reduced ethanol self-administration, while it did not modify
      saccharin self-administration. The same doses of the extract abolished the
      increased ethanol intake following ethanol deprivation. CONCLUSIONS: These
      findings provide evidence that HPCO2 markedly reduces the reinforcing properties
      of ethanol in the self-administration paradigm, as well as the increase of
      ethanol intake following ethanol deprivation. These findings further support the
      view that the use of HPE may represent an interesting pharmacological approach in
      the treatment of alcohol abuse and alcoholism.

PMID- 15870094
TI  - Clarification of cinnamoyl co-enzyme A reductase catalysis in monolignol
      biosynthesis of Aspen.
AB  - Cinnamoyl co-enzyme A reductase (CCR), one of the key enzymes involved in the
      biosynthesis of monolignols, has been thought to catalyze the conversion of
      several cinnamoyl-CoA esters to their respective cinnamaldehydes. However, it is
      unclear which cinnamoyl-CoA ester is metabolized for monolignol biosynthesis. A
      xylem-specific CCR cDNA was cloned from aspen (Populus tremuloides) developing
      xylem tissue. The recombinant CCR protein was produced through an Escherichia
      coli expression system and purified to electrophoretic homogeneity. The
      biochemical properties of CCR were characterized through direct structural
      corroboration and quantitative analysis of the reaction products using a liquid
      chromatography-mass spectrometry system. The enzyme kinetics demonstrated that
      CCR selectively catalyzed the reduction of feruloyl-CoA from a mixture of five
      cinnamoyl CoA esters. Furthermore, feruloyl-CoA showed a strong competitive
      inhibition of the CCR catalysis of other cinnamoyl CoA esters. Importantly, when
      CCR was coupled with caffeoyl-CoA O-methyltransferase (CCoAOMT) to catalyze the
      substrate caffeoyl-CoA ester, coniferaldehyde was formed, suggesting that CCoAOMT
      and CCR are neighboring enzymes. However, the in vitro results also revealed that
      the reactions mediated by these two neighboring enzymes require different pH
      environments, indicating that compartmentalization is probably needed for CCR and
      CCoAOMT to function properly in vivo. Eight CCR homologous genes were identified
      in the P. trichocarpa genome and their expression profiling suggests that they
      may function differentially.

PMID- 15870095
TI  - Caffeine inhibits callose deposition in the cell plate and the depolymerization
      of microtubules in the central region of the phragmoplast.
AB  - Treatment of tobacco BY-2 cells with 10 mM caffeine that was started after the
      cells had entered the mitotic phase did not completely inhibit the deposition of
      callose in the cell plate and allowed the centrifugal redistribution of
      phragmoplast microtubules. On the other hand, when treatment with caffeine was
      started before the cells entered the mitotic phase, the deposition of callose was
      completely inhibited and the redistribution of phragmoplast microtubules was also
      inhibited. As the inhibition of redistribution of phragmoplast microtubules seems
      to be caused by the inhibition of depolymerization of microtubules at the central
      region of the phragmoplast, these results strongly suggest that the deposition of
      callose in the cell plate is tightly linked with the depolymerization of
      phragmoplast microtubules. Callose deposition was observed in phragmoplasts
      isolated from caffeine-treated cells as well as in those isolated from non
      caffeine-treated cells, and caffeine did not inhibit callose synthesis in
      isolated phragmoplast, indicating that caffeine neither inhibits the accumulation
      of callose synthase at the equatorial regions of the phragmoplast nor arrests
      callose synthase itself.

PMID- 15870096
TI  - ALBINO AND PALE GREEN 10 encodes BBMII isomerase involved in histidine
      biosynthesis in Arabidopsis thaliana.
AB  - We isolated an Arabidopsis albino and pale green 10 (apg10) mutant which exhibits
      pale green cotyledons and true leaves at the juvenile stage. We identified a
      valine to leucine change in BBMII (N'-[(5'-phosphoribosyl)-formimino]-5
      aminoimidazole-4-carboxamide ribonucleotide) isomerase involved in histidine
      biosynthesis. The morphological abnormality of apg10 was recovered by histidine
      supplementation. The histidine limitation induced by apg10 mutation causes
      dynamic changes of the free amino acid profile, suggesting the existence of a
      cross-pathway regulatory mechanism of amino acid biosynthesis in plants. We also
      revealed that the APG10 knockout mutant exhibited embryo lethality, indicating
      the essential role of the Arabidopsis BBMII isomerase for plant growth.

PMID- 15870097
TI  - Salicylic acid accumulation under O3 exposure is regulated by ethylene in tobacco
      plants.
AB  - Ozone (O3), a major photochemical oxidant, induces leaf injury concomitant with
      salicylic acid (SA) synthesis. In pathogen-infected leaves, SA is synthesized via
      two pathways, involving phenylalanine or isochorismate. SA biosynthesis under O3
      fumigation is not well understood. When we applied 14C-labeled benzoic acid (a
      precursor of SA in the pathway via phenylalanine) to O3-exposed tobacco leaves,
      it was effectively metabolized to SA. However, the activity and mRNA level of
      isochorismate synthase (ICS) were not increased. In contrast, ICS activity was
      increased in O3-exposed Arabidopsis thaliana L. These results suggest that SA is
      synthesized via benzoic acid from phenylalanine in O3-exposed tobacco leaves but
      via isochorismate in Arabidopsis. Ethylene is a plant hormone that promotes leaf
      damage in O3-exposed plants. During O3 exposure, transgenic plants with a
      phenotype of reduced O3-induced ethylene production accumulated less SA than did
      wild-type plants. O3 increased the activity of phenylalanine ammonia-lyase (PAL)
      and the transcript levels of the chorismate mutase (CM) and PAL genes in wild
      type tobacco, but their induction was suppressed in the transgenic plants. These
      results indicate that ethylene promotes SA accumulation by regulating the
      expression of the CM and PAL genes in O3-exposed tobacco.

PMID- 15870098
TI  - Use of community pharmacies: a population-based survey.
AB  - BACKGROUND: Community pharmacies are widely used in the UK, but the services they
      provide are changing, with pharmacists expected to take on wider roles and
      responsibilities. The impact of such changes will partly depend on who uses
      pharmacies and their illnesses. METHODS: This was a cross-sectional survey of a
      stratified random sample of 10,000 adults aged 35 years plus. RESULTS: In the
      previous month, 59 per cent of respondents had collected a prescription medicine
      and 40 per cent had purchased an over-the-counter (OTC) medicine from a pharmacy,
      whereas only 12 per cent had asked for advice. Women were more likely to have
      obtained medicine or asked for advice (76 per cent), but nearly two-thirds of men
      had done so (63 per cent). Poor self-rated health was the key factor in obtaining
      medicine, both on prescription and OTC. Purchasers of OTC medicine were more
      likely to be younger and from higher socio-economic classes, whereas those who
      collected prescription medicine were more likely to be older, feel at risk of
      vascular health problems and non-smokers. Medicines to treat cold and flu
      symptoms were the most frequently reported purchase type. Only a small number of
      respondents who asked for advice had not also obtained medicine. Respondents who
      asked for advice were more likely to have asked about a specific medicine or
      illness than to have asked for general health advice. CONCLUSION: Whilst those
      with poorer health are more likely to visit, a wide range of ages and social
      classes visit pharmacies each month. This provides an opportunity for public
      health initiatives to be delivered in pharmacies.

PMID- 15870099
TI  - Mode of questionnaire administration can have serious effects on data quality.
AB  - BACKGROUND: One of the main primary data collection instruments in social, health
      and epidemiological research is the survey questionnaire. Modes of data
      collection by questionnaire differ in several ways, including the method of
      contacting respondents, the medium of delivering the questionnaire to
      respondents, and the administration of the questions. These are likely to have
      different effects on the quality of the data collected. METHODS: This paper is
      based on a narrative review of systematic and non-systematic searches of the
      literature on the effects of mode of questionnaire administration on data
      quality. RESULTS: Within different modes of questionnaire administration, there
      were many documented potential, biasing influences on the responses obtained.
      These were greatest between different types of mode (e.g. self-administered
      versus interview modes), rather than within modes. It can be difficult to
      separate out the effects of the different influences, at different levels.
      CONCLUSIONS: The biasing effects of mode of questionnaire administration has
      important implications for research methodology, the validity of the results of
      research, and for the soundness of public policy developed from evidence using
      questionnaire-based research. All users of questionnaires need to be aware of
      these potential effects on their data.

PMID- 15870100
TI  - Impact of UK Colorectal Cancer Screening Pilot on hospital diagnostic services.
AB  - OBJECTIVE: To determine the impact of the UK Colorectal Cancer Screening Pilot on
      hospital services involved in the diagnosis of colorectal cancer (predominantly
      colonoscopy, double contrast barium enema and pathology). METHODS: Routine data
      from seven hospitals at two sites within Scotland and England participating in
      the Pilot were collected on activity levels and waiting times for key hospital
      services (GI medicine, surgery and radiology), plus questionnaire survey data
      from hospital consultants. RESULTS: Hospital colonoscopy activity increased by 31
      per cent in Scotland and 21 per cent in England due to the investigation of
      faecal occult blood testing (FOBt) positive subjects. The demand for symptomatic
      (non-screening) colonoscopy also increased. Pilot-generated activity was less
      than predicted for barium enema services (maximum 3 per cent increase in service
      volume) but greater than expected for pathology, with approximately 200
      specimens/month generated. Out-patient review of Pilot colonoscopy patients and
      associated administrative duties added substantially to overall GI service
      workload, but quantification was limited by the quality of routinely available
      data. There was a wide discrepancy in colonoscopy waiting times between screened
      and symptomatic patients, with predominantly longer waits for symptomatic
      patients: otherwise the quality of colonoscopy services appeared to improve. In
      any future national screening programme, follow-up of patients with adenomas will
      result in a further increase of 28 per cent in the number of colonoscopies
      generated (over and above colonoscopy for FOBt-positive subjects), adding
      substantially to overall workload. CONCLUSIONS: During the planning of any
      successful national colorectal cancer screening programme, careful consideration
      must be given to the wider aspects of workload associated with screening, as well
      as to the implementation of appropriate hospital data collection systems.

PMID- 15870101
TI  - Neuronal deletion of Lepr elicits diabesity in mice without affecting cold
      tolerance or fertility.
AB  - Leptin signaling in the brain regulates energy intake and expenditure. To test
      the degree of functional neuronal leptin signaling required for the maintenance
      of body composition, fertility, and cold tolerance, transgenic mice expressing
      Cre in neurons (CaMKIIalpha-Cre) were crossed to mice carrying a floxed leptin
      receptor (Lepr) allele to generate mice with neuron-specific deletion of Lepr in
      approximately 50% (C F/F mice) and approximately 75% (C Delta17/F mice) of
      hypothalamic neurons. Leptin receptor (LEPR)-deficient mice (Delta17/Delta17)
      with heat-shock-Cre-mediated global Lepr deletion served as obese controls. At 16
      wk, male C F/F, C Delta17/F, and Delta17/Delta17 mice were 13.2 (P < 0.05), 45.0,
      and 55.9% (P < 0.001) heavier, respectively, than lean controls, whereas females
      showed 31.6, 68.8, and 160.7% increases in body mass (P < 0.001). Significant
      increases in total fat mass (C F/F: P < 0.01; C Delta17/F and Delta17/Delta17:P <
      0.001 vs. sex-matched, lean controls), and serum leptin concentrations (P < 0.001
      vs. controls) were present in proportion to Lepr deletion. Male C Delta17/F mice
      had significant elevations in basal serum insulin concentrations (P < 0.001 vs.
      controls) and were glucose intolerant, as measured by glucose tolerance test (AUC
      P < 0.01 vs. controls). In contrast with previous observations in mice null for
      LEPR signaling, C F/F and C Delta17/F mice were fertile and cold tolerant. These
      findings support the hypothesis that body weight, adiposity, serum leptin
      concentrations, and glucose intolerance are proportional to hypothalamic LEPR
      deficiency. However, fertility and cold tolerance remain intact unless
      hypothalamic LEPR deficiency is complete.

PMID- 15870102
TI  - Increases in glycogenin and glycogenin mRNA accompany glycogen resynthesis in
      human skeletal muscle.
AB  - Glycogenin is the self-glycosylating protein primer that initiates glycogen
      granule formation. To examine the role of this protein during glycogen
      resynthesis, eight male subjects exercised to exhaustion on a cycle ergometer at
      75% Vo2 max followed by five 30-s sprints at maximal capacity to further deplete
      glycogen stores. During recovery, carbohydrate (75 g/h) was supplied to promote
      rapid glycogen repletion, and muscle biopsies were obtained from the vastus
      lateralis at 0, 30, 120, and 300 min postexercise. At time 0, no free
      (deglycosylated) glycogenin was detected in muscle, indicating that all
      glycogenin was complexed to carbohydrate. Glycogenin activity, a measure of the
      glycosylating ability of the protein, increased at 30 min and remained elevated
      for the remainder of the study. Quantitative RT-PCR showed elevated glycogenin
      mRNA at 120 min followed by increases in protein levels at 300 min. Glycogenin
      specific activity (glycogenin activity/relative protein content) was also
      elevated at 120 min. Proglycogen increased at all time points, with the highest
      rate of resynthesis occurring between 0 and 30 min. In comparison, macroglycogen
      levels did not significantly increase until 300 min postexercise. Together, these
      results show that, during recovery from prolonged exhaustive exercise, glycogenin
      mRNA and protein content and activity increase in muscle. This may facilitate
      rapid glycogen resynthesis by providing the glycogenin backbone of proglycogen,
      the major component of glycogen synthesized in early recovery.

PMID- 15870103
TI  - Intraperitoneal infusion of proinflammatory cytokines does not cause activation
      of the rat uterus during late gestation.
AB  - Increased concentrations of IL-1beta and TNF-alpha have been associated with
      parturition. However, the role of these cytokines is unknown. Before parturition,
      the uterus undergoes a process of activation, during which there are significant
      changes in expression of genes associated with increased uterine contractility,
      including the receptors for oxytocin (OT) and prostaglandin (PG)F(2alpha) (FP),
      PGH(2) synthase isoform 2 (PGHS2), the gap junction protein connexin-43 (Cx-43),
      and the inducible isoform of nitric oxide synthase (iNOS). To determine whether
      IL-1beta or TNF-alpha was part of the causal mechanism for increased uterine
      contractions, we placed osmotic pumps infusing IL-1beta or TNF-alpha into the
      peritoneal cavity of late pregnant rats (gestation day 19) and measured the
      effects on uterine contractility and on the uterine concentrations of mRNA for
      the contraction-associated genes 24 h later. Maternal serum concentrations of IL
      1beta and TNF-alpha were increased significantly. By day 21, the control animals
      had significant increases (P < or = 0.05) in mRNA for OT, FP, PGHS2, and Cx-43, a
      decrease (P < or = 0.05) in iNOS, and an increase (P < or = 0.05) in uterine
      sensitivity and responsiveness to OT. Infusion of IL-1beta or TNF-alpha had no
      effect on uterine contractility or on expression of the activation-associated
      genes. We conclude that intraperitoneal infusion of IL-1beta or TNF-alpha
      resulting in significantly increased maternal serum cytokine levels does not
      cause uterine activation. The role of proinflammatory cytokines in the mechanism
      of parturition remains unclear.

PMID- 15870104
TI  - Three weeks of caloric restriction alters protein metabolism in normal-weight,
      young men.
AB  - The effects of prolonged caloric restriction (CR) on protein kinetics in lean
      subjects has not been investigated previously. The purpose of this study was to
      test the hypotheses that 21 days of CR in lean subjects would 1) result in
      significant losses of lean mass despite a suppression in leucine turnover and
      oxidation and 2) negatively impact exercise performance. Nine young, normal
      weight men [23 +/- 5 y, 78.6 +/- 5.7 kg, peak oxygen consumption (Vo2 peak) 45.2
      +/- 7.3 ml.kg(-1).min(-1), mean +/- SD] were underfed by 40% of the calories
      required to maintain body weight for 21 days and lost 3.8 +/- 0.3 kg body wt and
      2.0 +/- 0.4 kg lean mass. Protein intake was kept at 1.2 g.kg(-1).day(-1).
      Leucine kinetics were measured using alpha-ketoisocaproic acid reciprocal pool
      model in the postabsorptive state during rest and 50 min of exercise (EX) at 50%
      of Vo2 peak). Body composition, basal metabolic rate (BMR), and exercise
      performance were measured throughout the intervention. At rest, leucine flux
      (approximately 131 micromol.kg(-1).h(-1)) and oxidation (R(ox); approximately 19
      micromol.kg(-1).h(-1)) did not differ pre- and post-CR. During EX, leucine flux
      (129 +/- 6 vs. 121 +/- 6) and R(ox) (54 +/- 6 vs. 46 +/- 8) were lower after CR
      than they were pre-CR. Nitrogen balance was negative throughout the intervention
      ( approximately 3.0 g N/day), and BMR declined from 1,898 +/- 262 to 1,670 +/-
      203 kcal/day. Aerobic performance (Vo2 peak, endurance cycling) was not impacted
      by CR, but arm flexion endurance decreased by 20%. In conclusion, 3 wk of caloric
      restriction reduced leucine flux and R(ox) during exercise in normal-weight young
      men. However, despite negative nitrogen balance and loss of lean mass, whole body
      exercise performance was well maintained in response to CR.

PMID- 15870105
TI  - MAP kinase-mediated phosphorylation of distinct pools of histone H3 at S10 or S28
      via mitogen- and stress-activated kinase 1/2.
AB  - ERK and p38 MAP kinases, acting through the downstream mitogen- and stress
      activated kinase 1/2 (MSK1/2), elicit histone H3 phosphorylation on a subfraction
      of nucleosomes--including those at Fos and Jun--concomitant with gene induction.
      S10 and S28 on the H3 tail have both been shown to be phospho-acceptors in vivo.
      Both phospho-epitopes appear with similar time-courses and both occur on H3 tails
      that are highly sensitive to TSA-induced hyperacetylation, similarities which
      might suggest that MSK1/2 phosphorylates both sites on the same H3 tails. Indeed,
      on recombinant histone octamers in vitro, MSK1 efficiently phosphorylates both
      sites on the same H3 tail. However, sequential immunoprecipitation studies show
      that antibodies against phosphorylated S10-H3 recover virtually all this epitope
      without depletion of phosphorylated S28-H3, and vice versa, indicating that the
      two phospho-epitopes are not located on the same H3 tail in vivo. Confocal
      immunocytochemistry confirms the clear physical separation of the two phospho
      epitopes in the intact mouse nucleus. Finally, we used transfection-based
      experiments to test models that might explain such differential targeting.
      Overexpression and delocalisation of MSK1 does not result in the breakdown of
      targeting in vivo despite the fact that the ectopic kinase is fully activated by
      external stimuli. These studies reveal a remarkable level of targeting of S10 and
      S28 phosphorylation to distinct H3 tails within chromatin in the interphase mouse
      nucleus. Possible models for such exquisite targeting are discussed.

PMID- 15870106
TI  - SYCP2 and SYCP3 are required for cohesin core integrity at diplotene but not for
      centromere cohesion at the first meiotic division.
AB  - Much of the organization of the meiotic prophase-I chromosome axis is attributed
      to two groups of proteins: the axial element proteins, SYCP2 and SYCP3; and the
      cohesin-complex proteins. Although the cohesin-complex proteins ensure that
      sister chromatids remain paired during meiosis, the role of SYCP2 and SYCP3 is
      not clear. Interestingly, it has been shown that SYCP3 and SYCP2 associate with
      the centromere regions of male, but not female, metaphase-I chromosomes,
      suggesting a sex-specific function for the two proteins. We have analysed the
      spatial distribution of cohesin-complex proteins associated with meiotic
      chromosomes in germ cells derived from Sycp3-deficient female and male mice. We
      show that, in the absence of SYCP3, the cohesin cores associated with the female
      meiotic chromosomes disassemble prematurely at the diplotene stage of meiosis. We
      also show that SYCP3 and SYCP2 are not required for centromere cohesion at the
      metaphase-I stage in male germ cells. We conclude that SYCP3 has a temporally
      restricted role in maintaining, but not establishing, cohesin-core organization
      during prophase I. This finding supports a model in which the removal of bulk
      cohesin from paired sister chromatids at late prophase in both meiotic and
      mitotic cells ensures proper chromosome compaction and segregation.

PMID- 15870107
TI  - MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular
      network collapse and regression in 3D collagen matrices.
AB  - Previous work has shown that endothelial cell (EC)-derived matrix
      metalloproteinases (MMPs) regulate regression of capillary tubes in vitro in a
      plasmin- and MMP-1 dependent manner. Here we report that a number of serine
      proteases can activate MMP-1 and cause capillary tube regression; namely plasma
      kallikrein, trypsin, neutrophil elastase, cathepsin G, tryptase and chymase.
      Plasma prekallikrein failed to induce regression without coactivators such as
      high molecular weight kininogen (HMWK) or coagulation Factor XII. The addition of
      trypsin, the neutrophil serine proteases (neutrophil elastase and cathepsin G)
      and the mast cell serine proteases (tryptase and chymase) each caused MMP-1
      activation and collagen type I proteolysis, capillary tubular network collapse,
      regression and EC apoptosis. Capillary tube collapse is accompanied by collagen
      gel contraction, which is strongly related to the wound contraction that occurs
      during regression of granulation tissue in vivo. We also report that proMMP-10
      protein expression is markedly induced in ECs undergoing capillary tube
      morphogenesis. Addition of each of the serine proteases described above led to
      activation of proMMP-10, which also correlated with MMP-1 activation and
      capillary tube regression. Treatment of ECs with MMP-1 or MMP-10 siRNA markedly
      delayed capillary tube regression, whereas gelatinase A (MMP-2), gelatinase B
      (MMP-9) and stromelysin-1 (MMP-3) siRNA-treated cells behaved in a similar manner
      to controls and regressed normally. Increased expression of MMP-1 or MMP-10 in
      ECs using recombinant adenoviral delivery markedly accelerated serine protease
      induced capillary tube regression. ECs expressing increased levels of MMP-10
      activated MMP-1 to a greater degree than control ECs. Thus, MMP-10-induced
      activation of MMP-1 correlated with tube regression and gel contraction. In
      summary, our work demonstrates that MMP-1 zymogen activation is mediated by
      multiple serine proteases and MMP-10, and that these events are central to EC
      mediated collagen degradation and capillary tube regression in 3D collagen
      matrices.

PMID- 15870108
TI  - tGolgin-1 (p230, golgin-245) modulates Shiga-toxin transport to the Golgi and
      Golgi motility towards the microtubule-organizing centre.
AB  - tGolgin-1 (trans-Golgi p230, golgin-245) is a member of a family of large
      peripheral membrane proteins that associate with the trans-Golgi network (TGN)
      via a C-terminal GRIP domain. Some GRIP-domain proteins have been implicated in
      endosome-to-TGN transport but no function for tGolgin-1 has been described. Here,
      we show that tGolgin-1 production is required for efficient retrograde
      distribution of Shiga toxin from endosomes to the Golgi. Surprisingly, we also
      found an indirect requirement for tGolgin-1 in Golgi positioning. In HeLa cells
      depleted of tGolgin-1, the normally centralized Golgi and TGN membranes were
      displaced to the periphery, forming 'mini stacks'. These stacks resembled those
      in cells with disrupted microtubules or dynein-dynactin motor, in that they
      localized to endoplasmic-reticulum exit sites, maintained their secretory
      capacity and cis-trans polarity, and were relatively immobile by video
      microscopy. The mini stacks formed concomitant with a failure of pre-Golgi
      elements to migrate along microtubules towards the microtubule-organizing centre.
      The requirement for tGolgin-1 in Golgi positioning did not appear to reflect
      direct binding of tGolgin-1 to motile pre-Golgi membranes, because distinct Golgi
      and tGolgin-1-containing TGN elements that formed after recovery of HeLa cells
      from brefeldin-A treatment moved independently toward the microtubule-organizing
      centre. These data demonstrate that tGolgin-1 functions in Golgi positioning
      indirectly, probably by regulating retrograde movement of cargo required for
      recruitment or activation of dynein-dynactin complexes on newly formed Golgi
      elements.

PMID- 15870109
TI  - Expression of truncated latent TGF-beta-binding protein modulates TGF-beta
      signaling.
AB  - Transforming growth factor-beta is released from most cells as an inactive
      complex consisting of transforming growth factor-beta, the transforming growth
      factor-beta propeptide and the latent transforming growth factor-beta-binding
      protein. We studied the role of latent transforming growth factor-beta-binding
      protein in modulating transforming growth factor-beta availability by generating
      transgenic mice that express a truncated form of latent transforming growth
      factor-beta-binding protein-1 that binds to transforming growth factor-beta but
      is missing the known N- and C-terminal matrix-binding sequences. As transforming
      growth factor-beta is an inhibitor of keratinocyte proliferation and is involved
      in the control of hair cycling, we over-expressed the mutated form of latent
      transforming growth factor-beta-binding protein under the control of the keratin
      14-promoter. Transgenic animals displayed a hair phenotype due to a reduction in
      keratinocyte proliferation, an abbreviated growth phase and an early initiation
      of the involution (catagen) phase of the hair cycle. This phenotype appears to
      result from excess active transforming growth factor-beta, as enhanced numbers of
      pSmad2/3-positive nuclei are observed in transgenic animal skin. These data
      suggest that the truncated form of latent transforming growth factor-beta-binding
      protein-1 competes with wild-type latent transforming growth factor-beta-binding
      protein for binding to latent transforming growth factor-beta, resulting in
      latent transforming growth factor-beta complexes that fail to be targeted
      correctly in the extracellular matrix. The mis-localization of the transforming
      growth factor-beta results in inappropriate activation and premature initiation
      of catagen, thereby illustrating the significance of latent transforming growth
      factor-beta-binding protein interaction with transforming growth factor-beta in
      the targeting and activation of latent transforming growth factor-beta in
      addition to previously reported effects on small latent complex secretion.

PMID- 15870110
TI  - Two separate motifs cooperate to target stathmin-related proteins to the Golgi
      complex.
AB  - The appropriate targeting of membrane-associated proteins involves a diversity of
      motifs including post-translational modifications and specific protein sequences.
      Phosphoproteins of the stathmin family are important regulators of microtubule
      dynamics, in particular in the developing and mature nervous system. Whereas
      stathmin is cytosolic, SCG10, SCLIP and the splice variants RB3/RB3'/RB3'' are
      associated with Golgi and vesicular membranes, through their palmitoylated N
      terminal A domains. In order to identify essential motifs involved in this
      specific targeting, we examined the subcellular distribution of various
      subdomains derived from domain A of SCG10 fused with GFP. We show that the Golgi
      localization of SCG10 results from the cooperation of two motifs: a membrane
      anchoring palmitoylation motif and a newly identified Golgi-specifying sequence.
      The latter displayed no targeting activity by itself, but retained a Golgi
      specifying activity when associated with another membrane-anchoring
      palmitoylation motif derived from the protein GAP-43. We further identified
      critical residues for the specific Golgi targeting of domain A. Altogether, our
      results give new insight into the regulation of the subcellular localization of
      stathmin family proteins, an important feature of their physiological functions
      in differentiating and mature neural cells. More generally we provide new
      information on essential mechanisms of functional protein subcellular targeting.

PMID- 15870111
TI  - Association of hnRNP S1 proteins with vimentin intermediate filaments in
      migrating cells.
AB  - S1 proteins C2 and D2 are multifunctional hnRNP proteins acting as
      transcriptional regulators in the nucleus. Immunofluorescence staining of various
      cells in culture revealed that S1 proteins also occur in the cytoplasm, often in
      association with vimentin intermediate filaments (VFs). Here, we verified the
      association of S1 proteins with vimentin using vimentin-deficient cells,
      crosslinking and immunoprecipitation, and further investigated the biological
      significance of this association. S1 proteins on VFs, referred to here as S1
      fibers, were lost in highly confluent cells, where cell proliferation and
      cellular metabolic activity greatly decreased owing to cell density-dependent
      arrest. However, the disappearance of S1 fibers was not related to these reduced
      activities, but to inhibited cell migration. Although undetected in cells of non
      migratory tissues as well as in confluent cultured cells, S1 fibers were found in
      all migratory cells examined, such as cultured cells in scratch/wound
      experiments, blood neutrophils and monocytes, and fibroblasts engaging in tissue
      healing. In addition, S1 fibers reappeared even in confluent cells when VFs were
      induced to reorganize with okadaic acid. We propose that S1 proteins occur in
      association with VFs in migratory cells. Possible participation of S1 proteins in
      the formation/reorganization of VFs is discussed.

PMID- 15870112
TI  - Ryanodine receptor subtype 2 encodes Ca2+ oscillations activated by acetylcholine
      via the M2 muscarinic receptor/cADP-ribose signalling pathway in duodenum
      myocytes.
AB  - In this study, we characterized the signalling pathway activated by acetylcholine
      that encodes Ca2+ oscillations in rat duodenum myocytes. These oscillations were
      observed in intact myocytes after removal of external Ca2+, in permeabilized
      cells after abolition of the membrane potential and in the presence of heparin
      (an inhibitor of inositol 1,4,5-trisphosphate receptors) but were inhibited by
      ryanodine, indicating that they are dependent on Ca2+ release from intracellular
      stores through ryanodine receptors. Ca2+ oscillations were selectively inhibited
      by methoctramine (a M2 muscarinic receptor antagonist). The M2 muscarinic
      receptor-activated Ca2+ oscillations were inhibited by 8-bromo cyclic adenosine
      diphosphoribose and inhibitors of adenosine diphosphoribosyl cyclase (ZnCl2 and
      anti-CD38 antibody). Stimulation of ADP-ribosyl cyclase activity by acetylcholine
      was evaluated in permeabilized cells by measuring the production of cyclic
      guanosine diphosphoribose (a fluorescent compound), which resulted from the
      cyclization of nicotinamide guanine dinucleotide. As duodenum myocytes expressed
      the three subtypes of ryanodine receptors, an antisense strategy revealed that
      the ryanodine receptor subtype 2 alone was required to initiate the Ca2+
      oscillations induced by acetylcholine and also by cyclic adenosine
      diphosphoribose and rapamycin (a compound that induced uncoupling between 12/12.6
      kDa FK506-binding proteins and ryanodine receptors). Inhibition of cyclic
      adenosine diphosphoribose-induced Ca2+ oscillations, after rapamycin treatment,
      confirmed that both compounds interacted with the ryanodine receptor subtype 2.
      Our findings show for the first time that the M2 muscarinic receptor activation
      triggered Ca2+ oscillations in duodenum myocytes by activation of the cyclic
      adenosine diphosphoribose/FK506-binding protein/ryanodine receptor subtype 2
      signalling pathway.

PMID- 15870113
TI  - Regulation of skeletal muscle fiber type and slow myosin heavy chain 2 gene
      expression by inositol trisphosphate receptor 1.
AB  - Innervation-dependent signaling cascades that control activation of downstream
      transcription factors regulate expression of skeletal muscle fiber type-specific
      genes. Many of the innervation-regulated signaling cascades in skeletal muscle
      are dependent on intracellular calcium and the mechanisms by which calcium is
      released from the sarcoplasmic reticulum (SR). We report that the inositol
      trisphosphate receptor 1 (IP3R1), responsible for calcium release from the SR as
      a slow wave, was more abundant in fast contracting compared to slow contracting
      avian muscle fibers. Furthermore, inhibition of IP3R1 activity by 2
      aminoethoxydiphenylborate (2-APB) and xestospongin D induced a fiber type
      transition and expression of the slow myosin heavy chain 2 (slow MyHC2) gene in
      innervated fast muscle fibers. Activation of the slow MyHC2 promoter by IP3R1
      inhibition was accompanied by a reduction in protein kinase C activity. In
      addition, inhibition of IP3R1 activity resulted in a reduction of nuclear factor
      of activated T cells (NFAT)-dependent transcription and nuclear localization,
      indicating that IP3R1 activity regulated NFAT transcription factor activity in
      skeletal muscle fibers. Myocyte enhancer factor 2 (MEF2)-dependent
      transcriptional activity was increased by innervation, but unaffected by IP3R1
      activity. The results indicate that IP3R1 activity regulates muscle fiber type
      specific gene expression in innervated muscle fibers.

PMID- 15870114
TI  - Complexin II facilitates exocytotic release in mast cells by enhancing Ca2+
      sensitivity of the fusion process.
AB  - Recent studies have shown that soluble N-ethyl maleimide-sensitive factor
      attachment protein receptor (SNARE) proteins are involved in exocytotic release
      in mast cells as in neurotransmitter release. However, the roles of the proteins
      that regulate the structure and activity of SNARE proteins are poorly understood.
      Complexin is one such regulatory protein and is involved in neurotransmitter
      release, although ideas about its role are still controversial. In this study, we
      investigated the expression and role of complexin in the regulation of exocytotic
      release (degranulation) in mast cells. We found that complexin II, but not
      complexin I, is expressed in mast cells. We obtained RBL-2H3 cells that expressed
      a low level of complexin II and found that antigen-induced degranulation was
      suppressed in these cells. No significant changes in the Ca2+ response or
      expression levels of syntaxins and synaptotagmin were observed in knockdown
      cells. An immunocytochemical study revealed that complexin II was distributed
      throughout the cytoplasm before antigen stimulation. However, the distribution of
      complexin II changed dramatically with stimulation and it became localized on the
      plasma membrane. This change in the intracellular distribution was observed even
      in the absence of extracellular Ca2+, while exocytotic release was inhibited
      almost completely under this condition. The degranulation induced by phorbol 12
      myristate 13-acetate and A23187 depended on the extracellular Ca2+ concentration,
      and its sensitivity to Ca2+ was decreased in knockdown cells. These results
      suggest that complexin II regulates exocytosis positively by translocating to the
      plasma membrane and enhancing the Ca2+ sensitivity of fusion machinery, although
      this translocation to the plasma membrane is not sufficient to trigger exocytotic
      membrane fusion.

PMID- 15870115
TI  - Millionaires and mental health: Proposition 63 in California.
AB  - In November 2004 California passed Proposition 63, a landmark piece of mental
      health and fiscal legislation. This initiative places a 1 percent tax on adjusted
      gross income over dollar 1 million, affecting about 30,000 taxpayers and raising
      dollar 1.8 billion (a 31 percent increase) in new revenues over the first three
      years to support county-operated mental health systems. Our analysis suggests
      that Proposition 63 passed with strong support from Democrats, urban dwellers,
      and social workers and in counties with high rates of homelessness. Proposition
      63 faces challenges in implementation and provides unprecedented opportunities
      for transformation and change.

PMID- 15870116
TI  - Requirement of nuclear factor-kappaB in angiotensin II- and isoproterenol-induced
      cardiac hypertrophy in vivo.
AB  - BACKGROUND: In vitro experiments have proposed a role of nuclear factor-kappaB
      (NF-kappaB), a transcription factor, in cardiomyocyte hypertrophy and protection
      against apoptosis. Currently, the net effect on cardiac remodeling in vivo under
      common stress stimuli is unclear. METHODS AND RESULTS: We have generated mice
      with cardiomyocyte-restricted expression of the NF-kappaB super-repressor
      IkappaBalphaDeltaN (DeltaN(MHC)) using the Cre/lox technique. DeltaN(MHC) mice
      displayed an attenuated hypertrophic response compared with control mice on
      infusion of angiotensin II (Ang II) or isoproterenol by micro-osmotic pumps, as
      determined by echocardiography (left ventricular wall dimensions: control plus
      Ang II, x1.5+/-0.1 versus sham; DeltaN(MHC) plus Ang II, x1.1+/-0.1 versus sham;
      P<0.05; n> or =9), heart weight, and histological analysis. Real-time reverse
      transcriptase polymerase chain reaction showed significantly reduced expression
      of hypertrophy markers beta-myosin heavy chain and atrial natriuretic peptide in
      Ang II-treated DeltaN(MHC) mice (P<0.05 versus control plus Ang II; n=4). Neither
      cardiomyocyte apoptosis nor left ventricular dilatation was observed. In cultured
      adult rat cardiomyocytes, NF-kappaB DNA binding activity was increased by both
      Ang II- and interleukin-6-related cytokines. The latter are known to be released
      by cardiac fibroblasts on Ang II stimulation and thus could locally increase the
      NF-kappaB response of cardiomyocytes. Finally, results from in vitro and in vivo
      experiments suggest a role for NF-kappaB in the regulation of prohypertrophic
      interleukin-6 receptor gp130 on mRNA levels. CONCLUSIONS: These results indicate
      that targeted inhibition of NF-kappaB in cardiomyocytes in vivo is sufficient to
      impair Ang II- and isoproterenol-induced hypertrophy without increasing the
      susceptibility to apoptosis.

PMID- 15870117
TI  - Evidence-based vs. 'impressionist' medicine: how best to implement guidelines.
AB  - Implementing clinical practice guidelines improves outcomes. This has been shown
      by several large scale registries. However, in spite of this, guidelines are
      poorly implemented in clinical practice for a wide variety of reasons. We examine
      the reasons behind the low uptake of guidelines into routine medical practice.
      Many physicians are simply not aware that guidelines exist; or they do not
      believe in them; or they simply do not care to implement them. Economic and
      social factors may also influence uptake of guidelines. It is the role of
      professional societies to disseminate best scientific knowledge, and ensure
      optimum implementation of guidelines. This can be achieved through educational
      activities and CME credit. Close collaboration between the profession, health
      authorities, and maybe even the industry could improve uptake of clinical
      practice guidelines, and thereby improve patient outcome.

PMID- 15870118
TI  - Chronic fatigue in developing countries: population based survey of women in
      India.
AB  - OBJECTIVES: To describe the prevalence of and risk factors for chronic fatigue in
      a developing country; in particular, to determine the association of anaemia,
      mental health, and gender disadvantage factors with chronic fatigue. DESIGN:
      Community survey. SETTING: Primary health centre catchment area in Goa, India.
      PARTICIPANTS: 3000 randomly sampled women aged 18 to 50 years. MAIN OUTCOME
      MEASURES: Data on the primary outcome (reporting of fatigue for at least six
      months) and psychosocial exposures elicited by structured interview; presence of
      anaemia determined from a blood sample. RESULTS: 2494 (83%) women consented to
      participate; 12.1% (95% confidence interval 10.8 to 13.4%) complained of chronic
      fatigue. In multivariate analyses, older women (P = 0.03) and those experiencing
      socioeconomic deprivation-less education (P < 0.001), families in debt (P =
      0.09), or hunger in the past three months (P = 0.03)-were more likely to report
      chronic fatigue. After adjustment for these factors, factors indicating gender
      disadvantage (notably sexual violence by the husband; P < 0.001) and poor mental
      health (P < 0.001) were strongly associated with chronic fatigue. Although women
      with a high body mass index had a reduced risk, suggesting an influence of poor
      nutrition, no association was found between chronic fatigue and haemoglobin
      concentrations. CONCLUSIONS: Chronic fatigue was commonly reported by women in
      this community study from India. The strongest associations with chronic fatigue
      were for psychosocial factors indicative of poor mental health and gender
      disadvantage.

PMID- 15870119
TI  - Autosomal dominant resistance to thyrotropin as a distinct entity in five
      multigenerational kindreds: clinical characterization and exclusion of candidate
      loci.
AB  - CONTEXT: Resistance to TSH (RTSH) is an inherited disorder of variable
      hyposensitivity to TSH. The metabolic consequences can range from euthyroid
      hyperthyrotropinemia to severe congenital hypothyroidism with thyroid hypoplasia.
      Although subclinical and mild hypothyroidism fitting the RTSH phenotype is common
      in the population, the role of genetic factors is far from being understood. Only
      in rare cases has RTSH been attributed to TSHR or PAX8 gene mutations. OBJECTIVE,
      SETTING, AND PARTICIPANTS: Toward the identification of novel RTSH genes, we
      studied five large, unrelated families comprising 102 individuals, 56 of whom
      were affected. RESULTS: Inheritance of RTSH in these families followed an
      autosomal dominant pattern without evidence for incomplete penetrance, yet
      expressivity was variable. Considering only fully phenotyped generations, 64% of
      the progeny was affected, with a 1:1.4 male-to-female ratio. Of 18 affected
      individuals tested in the neonatal period, two were undetected because of
      borderline results. The thyroid phenotype was indistinguishable from that
      observed with PAX8 and TSHR defects. In four families, untreated affected
      subjects of all ages had elevated serum thyroglobulin levels, consistent with a
      defect in the thyroid follicle cells. Linkage of RTSH to TSHR and PAX8 was
      excluded in all five families. For the largest families, we likewise excluded a
      contribution of genes previously only associated with syndromic forms of RTSH,
      namely TITF1, GNAS, and FOXE1. CONCLUSIONS: These kindreds represent a distinct
      etiological entity of autosomal dominant RTSH. According to the clinical
      presentation of these families, genetic causes of mild hyperthyrotropinemia in
      the general population may be more common than currently appreciated.

PMID- 15870120
TI  - Transgenerational effects of posttraumatic stress disorder in babies of mothers
      exposed to the World Trade Center attacks during pregnancy.
AB  - CONTEXT: Reduced cortisol levels have been linked with vulnerability to
      posttraumatic stress disorder (PTSD) and the risk factor of parental PTSD in
      adult offspring of Holocaust survivors. OBJECTIVE: The purpose of this study was
      to report on the relationship between maternal PTSD symptoms and salivary
      cortisol levels in infants of mothers directly exposed to the World Trade Center
      collapse on September 11, 2001 during pregnancy. DESIGN: Mothers (n = 38)
      collected salivary cortisol samples from themselves and their 1-yr-old babies at
      awakening and at bedtime. RESULTS: Lower cortisol levels were observed in both
      mothers (F = 5.15, df = 1, 34; P = 0.030) and babies of mothers (F = 8.0, df = 1,
      29; P = 0.008) who developed PTSD in response to September 11 compared with
      mothers who did not develop PTSD and their babies. Lower cortisol levels were
      most apparent in babies born to mothers with PTSD exposed in their third
      trimesters. CONCLUSIONS: The data suggest that effects of maternal PTSD related
      to cortisol can be observed very early in the life of the offspring and
      underscore the relevance of in utero contributors to putative biological risk for
      PTSD.

PMID- 15870121
TI  - Regulation of neuroendocrine differentiation in gastrointestinal carcinoid tumor
      cells by notch signaling.
AB  - CONTEXT: Gastrointestinal (GI) carcinoid tumors elaborate serotonin and other
      vasoactive substances, causing the carcinoid syndrome. Based on developmental
      biology data, we hypothesized that basic helix-loop-helix transcription factors,
      including achaete-scute complex homolog-like 1 (Ascl1)/hASH1, and the Notch
      signaling pathway might regulate the neuroendocrine phenotype in GI carcinoids.
      OBJECTIVE: The aim of this study was to evaluate expression of developmental
      transcription factors and Notch signaling components in GI carcinoids and model
      their interaction in a relevant GI carcinoid cell line. DESIGN: Fourteen GI
      carcinoid tumor specimens, five paired adjacent normal tissues, fetal tissues,
      and tumor cell lines were analyzed by RT-PCR and immunoblot. BON carcinoid cells
      were further analyzed after Notch overexpression for neuroendocrine marker
      expression, serotonin production, and growth. SETTING: The study was conducted in
      an academic referral center. PATIENTS OR OTHER PARTICIPANTS: Deidentified
      archival pathology specimens were examined. RESULTS: Among a panel of six
      developmental transcription factors tested, only Ascl1 mRNA was overexpressed
      compared with surrounding normal tissue (seven of 10 GI carcinoid tumors and in
      BON cells, none of five normal tissues). Ascl1 protein was also expressed in four
      of four carcinoid tumors and BON cells). Notch pathway ligands, receptors, and
      downstream effectors were widely expressed in tumor and normal specimens.
      Overexpression of activated Notch1 in BON cells led to induction of the Notch
      effector hairy and enhancer of split 1 (Hes1), loss of Ascl1, reductions in
      neuron-specific enolase, synaptophysin, and chromogranin A, and most
      significantly, an 89% decrease in serotonin concentration and equivalent
      reductions in serotonin-reactive cells and repression of tryptophan hydroxylase 1
      mRNA. CONCLUSIONS: The Notch signaling pathway is a significant regulator of
      neuroendocrine differentiation and serotonin production in GI carcinoid tumors.

PMID- 15870122
TI  - Hypospadias in a cohort of 1072 Danish newborn boys: prevalence and relationship
      to placental weight, anthropometrical measurements at birth, and reproductive
      hormone levels at three months of age.
AB  - CONTEXT: Hypospadias is one of the most frequent male congenital malformations
      and may be part of the testicular dysgenesis syndrome. OBJECTIVE: The aim of the
      study was to investigate the prevalence of hypospadias in Denmark and evaluate
      the relationship to anthropometrical measurements at birth and reproductive
      hormone levels at 3 months of age. DESIGN: A prospective cohort study was
      conducted with 3-yr follow-up (1997-2004). SETTING: The population-based study
      was conducted at the University Hospital of Copenhagen. PARTICIPANTS: A total of
      1072 Danish boys were consecutively recruited antenatally, with 74.4% completing
      the study. MAIN OUTCOME MEASURES: The study examined the position of the urethral
      meatus, anthropometrical measurements, placental weight, and reproductive hormone
      levels. RESULTS: The Danish birth prevalence of hypospadias was significantly
      higher than in a concomitant Finnish study (1.03 vs. 0.27%; P = 0.012). At 3 yr,
      the true prevalence was found to be 4.64% because additional mild cases were
      detected when physiological phimosis dissolved. Weight for gestational age
      (percentage deviation from expected mean) (-5.00 vs. -0.59%; P = 0.030) and
      placental weight (567 vs. 658 g; P = 0.023) were significantly lower, and FSH was
      significantly higher (1.48 vs. 1.15 IU/liter; P = 0.007) in boys with
      hypospadias, compared with healthy boys. CONCLUSIONS: We found a surprisingly
      high total rate of hypospadias of 4.6% in this large prospective cohort study.
      Seventy-two percent of the cases were apparent only after the prepuce could be
      retracted. Hypospadias were associated with elevated serum FSH levels at 3
      months. We also confirmed an association between fetal growth impairment and
      hypospadias; however, it is yet unknown whether this indicates a causal
      relationship or a shared pathogenic factor.

PMID- 15870123
TI  - Endothelial function, carotid artery intima-media thickness, epicardial adipose
      tissue, and left ventricular mass and function in growth hormone-deficient
      adolescents: apparent effects of growth hormone treatment on these parameters.
AB  - OBJECTIVE: The purpose of this study was to determine whether GH-deficient (GHD)
      adolescents have abnormalities of cardiac and vascular function detectable during
      the teenage years. DESIGN/METHODS: Ten GHD children on GH treatment with a
      chronological age (CA) of 14.6 +/- 1.7 yr and 12 untreated GHD adolescents with a
      CA of 15.0 +/- 3.0 yr were studied. Cardiac mass and function, carotid artery
      intima-media thickness, flow-mediated endothelium-dependent vasodilation (percent
      change from baseline diameter during hyperemia), and hyperemia-induced blood flow
      increase of the brachial artery (percent change from baseline) and epicardial
      adipose tissue were evaluated by echocardiography. Fourteen healthy adolescents
      served as controls. RESULTS: Untreated GHD adolescents present with a reduced
      left ventricular mass when compared with controls (P < 0.05) and a lower flow
      mediated endothelium-dependent increase in the diameter of the brachial artery
      during hyperemia than both controls and treated GHD subjects (P < 0.02), whereas
      their epicardial adipose tissue is significantly higher than that of healthy
      controls (P < 0.02). Interventricular septum thickness, posterior wall thickness,
      left ventricular ejection fraction, and carotid artery intima-media thickness
      were similar in all three groups. Hyperemia-induced blood flow increase was
      greater in treated GHD adolescents than both untreated subjects and controls (P <
      0.001). Body mass index correlated positively with epicardial adipose tissue in
      all three groups and with carotid intima-media thickness in treated and untreated
      GHD adolescents. CONCLUSIONS: GHD adolescents have a reduced left ventricular
      mass and vascular abnormalities manifested by lower flow-mediated endothelium
      dependent vasodilation. These findings together with an increase in epicardial
      adipose tissue, a good indicator of abdominal/visceral fat, may contribute to an
      increased cardiovascular risk in the long term. An improvement in endothelial
      function and a reduction in arterial stiffness appear to occur after GH
      replacement.

PMID- 15870124
TI  - Nicotine inhibits pulsatile luteinizing hormone secretion in human males but not
      in human females, and tolerance to this nicotine effect is lost within one week
      of quitting smoking.
AB  - CONTEXT AND OBJECTIVE: Despite having increased knowledge of the adverse
      reproductive effects of smoking, it is unclear whether nicotine affects the
      pulsatile LH secretion in humans. We addressed this issue in male and female
      smokers and nonsmokers. SUBJECTS AND METHODS: Twenty-nine male and 16 female
      nonsmokers and smokers were recruited as volunteers. In male smokers, nicotine
      effect was also studied before and after quitting smoking. In females, cyclic
      ovulatory function was assessed by measuring basal body temperature, and sampling
      studies were performed during the follicular phase. In the morning of the
      sampling day, an iv catheter was inserted into an anterobrachial vein, and blood
      samples (1.0-1.5 ml each) were taken at 10-min intervals for 480 min, during
      which, at 240 min, nicotine was administered via a transdermal patch (Nicotinell
      transdermal therapeutic system) containing 17.5 mg nicotine. Plasma LH was
      measured by immunoradiometric assay kits. RESULTS: Nicotine significantly
      lengthened the interpulse interval of pulsatile LH secretion in male nonsmokers
      but not in female nonsmokers. In male smokers, nicotine did not lengthen the
      interpulse interval, and in female smokers it was also ineffective. After
      quitting cigarette smoking in male smokers, the refractory to nicotine effect
      disappeared within 1 wk. CONCLUSIONS: We conclude that nicotine inhibits
      pulsatile LH secretion only in males, and the tolerance developed to the nicotine
      effect disappears within 1 wk of quitting cigarette smoking. However, we cannot
      deny the possibility that nicotine effect would have been detected in females if
      more subjects had been studied.

PMID- 15870126
TI  - Effects of aging on cytochrome b5 expression in the human adrenal gland.
AB  - CONTEXT: Aging in humans is characterized by a selective decline in circulating
      levels of adrenal androgens. The results of in vivo studies are suggestive of
      reduced adrenal 17,20-lyase activity in aging men and women. OBJECTIVE: We sought
      to determine whether there are changes in the distribution and/or expression of
      cytochrome B5 (CytB5), an accessory protein important in the regulation of 17,20
      lyase activity, in the adrenals of aging humans. DESIGN: Comparison between
      younger and older adrenal glands. SETTING: The study was conducted in a
      University Center. PATIENTS OR OTHER PARTICIPANTS: Adrenal glands obtained at
      autopsy after sudden death as a result of trauma from 46 young (age 20-40 yr) and
      26 older (age 50-91 yr) humans were obtained and fixed within 24 h postmortem.
      INTERVENTIONS: Paraffin sections were stained with hematoxylin and eosin and also
      were subjected to immunohistochemical staining for CytB5. All sections were
      quantitatively evaluated using an image capture and analysis program and
      qualitatively evaluated with respect to staining intensity. MAIN OUTCOME
      MEASURES: To determine whether there are any changes in CytB5 distribution in the
      adult human adrenal cortex during the aging process using qualitative and
      quantitative analysis with respect to age, gender, race, and postmortem interval.
      RESULTS: CytB5 immunoreactivity was found in cells that corresponded to those of
      the zona reticularis. The percentage of the adrenal cortex immunoreactive for
      CytB5 decreased with aging (38.6 +/- 7.6% for young and 30.1 +/- 5.9% for older,
      mean +/- sd; P < 0.0001) as did the percentage of adrenocortical tissue
      comprising the zona reticularis (36.8 +/- 10.8% for young and 27.2 +/- 5.9% for
      older; P < 0.001). However, there was no apparent change in the staining
      intensity of CytB5 among those cells that were immunopositive for this factor
      with aging. CONCLUSIONS: There appears to be a reduction in the proportion of the
      adrenal cortex that expresses CytB5 with aging, and this likely corresponds to a
      shrinkage of the zona reticularis. The mechanism and cause for this cortical
      regression are unknown.

PMID- 15870125
TI  - The relationships of adiponectin with insulin and lipids are strengthened with
      increasing adiposity.
AB  - CONTEXT: Adipose tissue inflammation has been implicated in the pathogenesis of
      obesity-related comorbidities. Adiponectin, an antiinflammatory protein, improves
      insulin sensitivity and lipid levels systemically. Because adiponectin is
      secreted by adipocytes, it may also act locally to counteract insulin resistance
      and dyslipidemia worsened by inflammation. OBJECTIVE: The aim of this study was
      to determine whether associations between adiponectin and insulin sensitivity and
      lipids are stronger with increasing adiposity. DESIGN: This cross-sectional study
      involved participants in The Princeton School District Study. SETTING: The study
      was conducted in the Princeton City schools (Cincinnati, OH) during the 2001-2002
      school year. PARTICIPANTS: A total of 1196 non-Hispanic White and Black students
      in grades 5-12 participated. MAIN OUTCOME MEASURE: The relationships between
      adiponectin and high-density lipoprotein, triglycerides, and insulin were
      measured. To test our hypothesis, we: 1) compared correlation and regression
      coefficients of lean and nonlean individuals, and 2) incorporated an adiponectin
      by adiposity interaction in regression models. RESULTS: For high-density
      lipoprotein and triglycerides, the relationship with adiponectin, although
      present among lean adolescents, strengthened with increasing adiposity. However,
      with insulin, a relationship with adiponectin was only present among nonlean
      adolescents. CONCLUSIONS: These analyses suggest that adiponectin's relationship
      with insulin and lipids strengthens with increasing adiposity, such that heavier
      adolescents have a greater benefit from high levels of adiponectin than their
      lean counterparts.

PMID- 15870127
TI  - Voice abnormality in adults with congenital and adult-acquired growth hormone
      deficiency.
AB  - CONTEXT: Adult males with congenital, untreated, severe GH deficiency (GHD) due
      to genetic GHRH receptor deficiency exhibit distinctive, high-pitched, and raspy
      voice characteristics. OBJECTIVE/DESIGN: To determine the physical underpinning
      of this phenomenon, we performed voice recordings, translarynx impedance
      measurements, spectral analysis, and estimates of spectral complexity
      [approximate entropy (ApEn)] in four affected men. Results were compared with
      those obtained in four men with untreated adult-onset GHD and a normal male
      population. RESULTS: Congenital GHD subjects had a high-pitched voice with a
      fundamental frequency typical of normal females (174-266 Hz). Their frequency
      spectra were characterized by abnormal harmonics, with reversal/interruption of
      the normal amplitude decay among higher-order harmonics, findings consistent with
      a creaky quality of the voice. Patients with adult-onset GHD, acquired at ages
      31, 38, and 40 yr, had a normal male pitch (fundamental frequency, 117-154 Hz)
      but pathologically low ApEn values, corresponding to a breathy quality of the
      voice and suggesting abnormal vocal fold function. A fourth patient who acquired
      GHD at age 22 yr had a pitch intermediate between male and female, high ApEn, and
      a spectral pattern similar to the congenital GHD patients. CONCLUSIONS: This
      study demonstrates an effect of GH on laryngeal size and vocal fold compliance
      that results in a high pitch and disordered spectral quality. The time of onset
      of GHD determines which type of abnormality predominates.

PMID- 15870128
TI  - Small differences in thyroid function may be important for body mass index and
      the occurrence of obesity in the population.
AB  - CONTEXT: Increasing prevalence of overweight in the population is a major concern
      globally; and in the United States, nearly one third of adults were classified as
      obese at the end of the 20th century. Few data have been presented regarding an
      association between variations in thyroid function seen in the general population
      and body weight. OBJECTIVE: The aim of this study was to investigate the
      association between thyroid function and body mass index (BMI) or obesity in a
      normal population. DESIGN: A cross-sectional population study (The DanThyr Study)
      was conducted. PARTICIPANTS: In all, 4649 participants were investigated, and
      4082 were eligible for these analyses after exclusion of subjects with previous
      or present overt thyroid dysfunction. MAIN OUTCOME MEASURES: The study examined
      the association between category of serum TSH or serum thyroid hormones and BMI
      or obesity in multivariate models, adjusting for possible confounding. RESULTS:
      We found a positive association between BMI and category of serum TSH (P < 0.001)
      and a negative association between BMI and category of serum free T(4) (P <
      0.001). No association was found between BMI and serum free T(3) levels. The
      difference in BMI between the groups with the highest and lowest serum TSH levels
      was 1.9 kg/m(2), corresponding to a difference in body weight of 5.5 kg among
      women. Similarly, the category of serum TSH correlated positively with weight
      gain during 5 yr (P = 0.04), but no statistically significant association was
      found with weight gain during 6 months (P = 0.17). There was an association
      between obesity (BMI > 30 kg/m(2)) and serum TSH levels (P = 0.001). CONCLUSIONS:
      Our results suggest that thyroid function (also within the normal range) could be
      one of several factors acting in concert to determine body weight in a
      population. Even slightly elevated serum TSH levels are associated with an
      increase in the occurrence of obesity.

PMID- 15870129
TI  - A prospective, randomized, double-blind study to compare two doses of recombinant
      human chorionic gonadotropin in inducing final oocyte maturity and the hormonal
      profile during the luteal phase.
AB  - CONTEXT: Different doses of human chorionic gonadotropin (hCG) have been used in
      various in vitro fertilization (IVF) treatment protocols to achieve final oocyte
      maturation. There is as yet no agreement on the optimum dose required.
      OBJECTIVES: The objective of this study was to compare the effectiveness of 250
      and 500 microg recombinant hCG (r-hCG), which represented the lower and upper
      limits of the dose range, in inducing final oocyte maturation during IVF and
      intracytoplasmic sperm injection cycles. DESIGN: This was a prospective,
      randomized, double-blind study. SETTING: This study was performed at an IVF
      clinic in a teaching hospital. PATIENTS: Sixty patients with an indication for
      intracytoplasmic sperm injection were studied. INTERVENTION: The treatment dose
      used was 250 or 500 microg r-hCG. MAIN OUTCOME MEASURES: The percentage of
      metaphase II oocytes retrieved per patient, as an indicator of oocyte maturation,
      and the hormone profiles of the treatment cycle starting from the day of hCG up
      to hCG+10 d were the main outcome measures. RESULTS: The percentage of metaphase
      II oocytes was similar in the two groups (89.3% vs. 86.0%; P = 0.326) despite
      higher serum and follicular fluid hCG levels on hCG+2 and hCG+4 d, as was the
      follicular fluid to serum hCG ratio in the 500-microg r-hCG group. Serum
      estradiol and progesterone levels were comparable initially, but became
      significantly higher in the 500-microg r-hCG group on hCG+10 d. CONCLUSION: The
      two doses of r-hCG were equally effective in inducing final oocyte maturation. It
      remains unclear whether the higher midluteal estradiol and progesterone levels in
      the 500-microg r-hCG group confer any benefit.

PMID- 15870130
TI  - Differential effects of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on
      prostate cancer cell signaling and death.
AB  - CONTEXT: GnRH is known to directly regulate prostate cancer cell proliferation,
      but the precise mechanism of action of the peptide is still under investigation.
      OBJECTIVE: This study demonstrates differential effects of GnRH-I and GnRH-II on
      androgen-independent human prostate cancer cells. RESULTS: Both GnRH-I and GnRH
      II increased the intracellular Ca(2+) concentration ([Ca(2+)](i)) either through
      Ca(2+) influx from external Ca(2+) source or via mobilization of Ca(2+) from
      internal Ca(2+) stores. Interestingly, the [Ca(2+)](i) increase was mediated by
      activation of the ryanodine receptor but not the inositol trisphosphate receptor.
      Trptorelix-1, a novel GnRH-II antagonist but not cetrorelix, a classical GnRH-I
      antagonist, completely inhibited the GnRH-II-induced [Ca(2+)](i) increase.
      Concurrently at high concentrations, trptorelix-1 and cetrorelix inhibited GnRH-I
      induced [Ca(2+)](i) increase, whereas at low concentrations they exerted an
      agonistic action, inducing Ca(2+) influx. High concentrations of trptorelix-1 but
      not cetrorelix-induced prostate cancer cell death, probably through an apoptotic
      process. Using photoaffinity labeling with (125)I-[azidobenzoyl-D-Lys(6)]GnRH-II,
      we observed that an 80-kDa protein specifically bound to GnRH-II. CONCLUSIONS:
      This study suggests the existence of a novel GnRH-II binding protein, in addition
      to a conventional GnRH-I receptor, in prostate cancer cells. These data may
      facilitate the development of innovatory therapeutic drugs for the treatment of
      prostate cancer.

PMID- 15870131
TI  - Coincidence of multiple endocrine neoplasia types 1 and 2: mutations in the RET
      protooncogene and MEN1 tumor suppressor gene in a family presenting with
      recurrent primary hyperparathyroidism.
AB  - CONTEXT: Primary hyperparathyroidism (HPT) presents as a part of inherited
      syndromes such as multiple endocrine neoplasia (MEN) types 1 and 2. In patients
      with MEN1, parathyroid hyperplasia or multiple adenomas occur in approximately 90
      95%. MEN2A-related HPT is characterized by a mild hypercalcemia, which is mostly
      asymptomatic. OBJECTIVE: Here we present a family with coexistence of MEN1 gene
      mutation and RET mutation. RESULTS: Six family members carrying MEN1 gene
      mutation IVS5 + 1G>A only, one family member with RET mutation Y791F, and three
      family members with both MEN1 gene and RET mutation were studied. The key to
      diagnosis was recurrent HPT in a young male carrying RET mutation Y791F, a
      mutation not likely to give rise to recurrent HPT. CONCLUSION: MEN1 gene mutation
      and RET codon 791 mutation in the same patient did not affect the typical
      phenotype of MEN1 or MEN2, and also the course of diseases seems to be unchanged.
      The reason may be that both mutations, although contributing to tumor
      pathogenesis, do not interact and induce a worsening of the cancer syndromes.

PMID- 15870132
TI  - Vascular dysfunction and metabolic parameters in polycystic ovary syndrome.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is associated with insulin resistance
      (IR) and the metabolic syndrome; however, the cardiovascular (CV) manifestations
      of PCOS remain unclear. OBJECTIVE: The objective of this study was to examine the
      relationships between IR, metabolic parameters, androgens, and markers of early
      CV disease in PCOS. DESIGN: We conducted an observational study examining
      noninvasive markers of early CV disease in women with PCOS including structural
      [carotid intimal media thickness (IMT)] and functional measures (arterial
      function with pulse wave velocity and endothelial function with brachial arterial
      flow-mediated vasodilation). Metabolic parameters included insulin and glucose
      during an oral glucose tolerance test and lipid and androgen levels. SETTING:
      Participants were recruited from the general community. PATIENTS: Eighty
      overweight women with PCOS who were nonsmokers and not on oral contraceptives or
      other medications known to affect IR participated in the study. RESULTS: Stepwise
      regression analysis showed that after adjustment for age and body mass index, IMT
      was significantly correlated with blood pressure (BP) load (P = 0.03) and
      inversely with dehydroepiandrosterone sulfate (DHEAS) (P = 0.01). After
      correction for androgen status, IMT was correlated with fasting glucose and area
      under curve (AUC) insulin. Flow-mediated vasodilation was inversely related to
      lipids (P = 0.02), whereas pulse wave velocity was related to BP (P < 0.001), AUC
      insulin (P = 0.04), and AUC glucose (P = 0.035). CONCLUSION: In overweight women
      with PCOS, insulin resistance and BP interacted negatively with arterial
      structural and functional measures. DHEAS correlated inversely with arterial
      structure, suggesting possible cardioprotective effects of endogenous DHEAS in
      women with PCOS. Additional research is needed to clarify these findings.

PMID- 15870133
TI  - Influence of human body composition on serum peak thyrotropin (TSH) after
      recombinant human TSH administration in patients with differentiated thyroid
      carcinoma.
AB  - OBJECTIVES: In this study, we evaluated the influence of height, weight, body
      mass index (BMI), body surface area, and body composition [total lean body mass
      (LBM) and fat body mass] on serum peak TSH levels obtained after recombinant
      human (rh)TSH. Furthermore, to verify whether the serum peak TSH influenced the
      efficacy of radioiodine ((131)I), we compared the rate of thyroid remnant
      ablation according to the patients' BMI. PATIENTS: We studied 105 patients with
      differentiated thyroid carcinoma who underwent rhTSH stimulation test. Serum TSH
      measurements were performed before and 24, 48, and 72 h after rhTSH
      administration. We also compared the rate of thyroid remnant ablation among 70
      differentiated thyroid carcinoma patients with different BMI. RESULTS: The serum
      peak TSH after rhTSH was significantly lower in overweight and obese subjects
      compared with normal-weight subjects (92.1 +/- 41.8, 82.4 +/- 24.2, and 112.7 +/-
      46.3 microU/ml, respectively; P = 0.01) and in males compared with females (74.6
      +/- 22.3 and 105.0 +/- 43.0 microU/ml, respectively; P = 0.0002). By univariate
      analysis, serum peak TSH was negatively related to weight, height, body surface
      area, BMI, LBM, and fat body mass, but only LBM was independently associated with
      serum peak TSH levels. Although it was confirmed that overweight and obese
      patients had a lower serum peak TSH, the rate of ablation did not differ among
      normal-weight, overweight, and obese patients. CONCLUSIONS: With this study we
      demonstrated that LBM is the only parameter independently associated with serum
      peak TSH after rhTSH administration. However, the serum peak TSH does not
      influence the rate of (131)I remnant ablation.

PMID- 15870135
TI  - Pure red cell aplasia associated with dapsone therapy.

PMID- 15870134
TI  - Increased serum resistin in adults with prader-willi syndrome is related to
      obesity and not to insulin resistance.
AB  - CONTEXT: Determinants of insulin resistance in Prader-Willi syndrome (PWS) are
      not completely understood. The discovery of several adipokines with relevant
      effects on insulin resistance and cardiovascular complications of metabolic
      syndrome offered new tools of investigation of insulin resistance in PWS.
      OBJECTIVE: The purpose of this study was to measure serum resistin and mRNA in
      adipose tissue of patients with PWS, those with simple obesity, and healthy
      controls and correlate resistin levels with anthropometric and biochemical
      features. DESIGN: Twenty-eight adult PWS patients, 29 obese patients, and 25
      healthy controls were studied. Anthropometric variables were measured and fasting
      serum and plasma were collected for measurement of resistin, adiponectin, leptin,
      lipid profile, glucose, and insulin. RESULTS: Serum resistin and resistin mRNA
      expression in adipose tissue was significantly higher in PWS patients, compared
      with both healthy lean controls and obese patients. Moreover, on regression
      analysis resistin was significantly correlated with body mass index, whereas no
      significant association was found between resistin and homeostasis model
      assessment index. A weak association between resistin and adiponectin was found
      in the PWS group only. However, on multivariate analysis only the correlation
      between resistin and body mass index remained significant. CONCLUSIONS: These
      results support a link between circulating resistin and obesity in humans but do
      not support a role for resistin in human insulin resistance.

PMID- 15870136
TI  - Acceleration of left-ventricular diastolic dysfunction and pulmonary hypertension
      after TNF-alpha blocker.

PMID- 15870137
TI  - Atomoxetine ingestions in children: a report from poison centers.
AB  - BACKGROUND: Atomoxetine uses a novel non-stimulant approach to the treatment of
      attention deficit hyperactivity disorder. There is limited information on
      overdose of atomoxetine in children or adults. OBJECTIVE: To provide information
      on atomoxetine in overdose. METHODS: Case series were conducted at 3 regional
      poison centers for atomoxetine ingestion in children (age < or = 17 y). Exclusion
      criteria were polypharmacy or lack of follow-up. RESULTS: Forty patients were
      included (25 boys; 63%) in the study. The mean +/- SD age was 6.1 +/- 4.9 years
      (range 9 mo-17 y). Twenty-five patients were managed at home, 14 in hospital
      emergency departments (3 children were admitted), and 1 patient was managed in a
      physician's office. Symptoms reported were tachycardia, drowsiness, nausea,
      hypertension, and vomiting. A seizure was reported in one child who had recently
      started atomoxetine therapy. No arrhythmias beyond sinus tachycardia were
      reported. Mean maximum heart rate in patients with tachycardia was 131 +/- 14
      beats/min. The mean dose ingested, categorized by medical outcome, was: no effect
      (n = 22), 40 +/- 32 mg; minor effect (n = 14), 167 +/- 221 mg; and moderate
      effect (n = 4), 249 +/- 326 mg. There were no major outcomes or fatalities. The
      lowest dose ingested that resulted in hypertension was 480 mg, in a 14-year-old
      girl (BP 136/95 mm Hg). CONCLUSIONS: In this case series, clinically significant
      cardiovascular effects requiring direct intervention did not occur. Activated
      charcoal and/or observation appear to be sufficient for accidental ingestion.
      Further investigation may be needed to indicate whether seizures occur from
      atomoxetine ingestion.

PMID- 15870138
TI  - Use of gabapentin for rest pain in chronic critical limb ischemia.

PMID- 15870139
TI  - Tramadol exposures reported to statewide poison control system.
AB  - BACKGROUND: Tramadol is a unique analgesic that has been associated with seizures
      on overdose. OBJECTIVE: To determine the toxic effects associated with tramadol
      exposure. METHODS: A retrospective chart review of tramadol exposures reported to
      a multisite, state-wide poison control system over a 2.5-year period was
      performed. RESULTS: A total of 602 cases were retrieved; 190 had sufficient data
      for study evaluation. Cases with coingestants or unknown outcomes were
      eliminated. Of the 190 remaining cases, 55% were females. Acute ingestions
      represented 90.0%, chronic ingestions 7.9%, and acute on chronic 2.1% of the
      overdoses. Ages of the patients ranged from 9 months to 80 years. Suicide
      attempts represented the largest group of exposures. Main symptoms included
      central nervous system (CNS) depression (27.4%), nausea and vomiting (21.1%),
      tachycardia (17.4%), and seizures (13.7%). Dosage ranged from a taste amount to
      5000 mg. The smallest amount of tramadol associated with seizure was 200 mg, and
      84.6% of seizures occurred within 6 hours of time of ingestion. Logistic
      regression analysis showed an association between seizures and tramadol use in
      males, chronic use, suicide attempts, intentional abuse or misuse, and
      tachycardia (HR >100 beats/min). No effect was seen in 36.3% of patients, minor
      effects in 43.7%, moderate effects in 19.5%, and major effects in 0.5%. Symptoms
      resolved within 24 hours in 96.7% of the 121 patients who had symptoms. Naloxone
      improved CNS depression in 7 of 8 patients in whom a response was documented.
      CONCLUSIONS: Tramadol overdoses frequently cause CNS depression, nausea/vomiting,
      tachycardia, and seizures. Symptoms generally resolve within 24 hours. Accidental
      ingestions in children were well tolerated, primarily causing sedation.

PMID- 15870140
TI  - Impact of nonsteroidal antiinflammatory drugs on the cardioprotective effects of
      aspirin.
AB  - OBJECTIVE: To examine the evidence of a pharmacodynamic interaction between
      aspirin and nonsteroidal antiinflammatory drugs (NSAIDs); specifically, to
      determine whether a deleterious relationship exists with respect to the
      cardioprotective effects of aspirin. DATA SOURCES: Primary articles were
      identified by a MEDLINE search (1966-May 2004). Search terms included aspirin,
      nonsteroidal antiinflammatory drug, drug interaction, mortality, myocardial
      infarction, and stroke. STUDY SELECTION AND DATA EXTRACTION: All prospective and
      retrospective studies conducted in human subjects and investigating the potential
      interaction between aspirin and NSAIDs were included. DATA SYNTHESIS: Several
      controlled pharmacodynamic studies indicate that the sustained inhibition of
      cyclooxygenase activity by aspirin is blunted in the presence of some NSAIDs.
      While these data are fairly consistent, they are limited in that they rely on
      surrogate markers and not clinical outcomes. Observational studies have shown
      conflicting results regarding the effect of combination NSAID and aspirin therapy
      on mortality risk and incidence of myocardial infarction. CONCLUSIONS:
      Pharmacodynamic data indicating an interaction between aspirin and NSAIDs have
      not translated to a consistent clinical effect in observational studies. In the
      absence of a randomized, controlled, clinical outcomes study, there is
      insufficient evidence to dictate a change in therapy.

PMID- 15870141
TI  - Nelarabine: a nucleoside analog with efficacy in T-cell and other leukemias.
AB  - OBJECTIVE: To present the pharmacology and pharmacokinetics of nelarabine, 9-beta
      D-arabinofuranosylguanine (ara-G) and intraleukemic cellular pharmacokinetics of
      9-beta-D-arabinofuranosylguanine triphosphate (ara-GTP) generated from the
      administration of nelarabine, and clinical and safety information relative to
      nelarabine use in the treatment of hematologic malignancies. DATA SOURCES:
      MEDLINE (1966-December 2004) was searched using the English-language key terms 2
      amino-6-methoxypurine arabinoside, 506U78, and nelarabine. Data were also
      obtained from published abstracts. STUDY SELECTION AND DATA EXTRACTION: Clinical
      studies evaluating the pharmacokinetics of nelarabine, ara-G, and cellular ara
      GTP and use of nelarabine, alone or in combination with other agents for the
      treatment of hematologic malignancies, were included in this review. DATA
      SYNTHESIS: Nelarabine is the water-soluble, 6-methoxy analog of 9-beta-D-ara-G.
      Nelarabine is readily converted to ara-G by endogenous adenosine deaminase. The
      half-life of nelarabine is approximately 15 minutes compared with 2-4 hours for
      ara-G. The clearance of ara-G is higher in children than in adults (0.312 vs
      0.213 L x h(-1) x kg(-1)). Intracellular ara-GTP elimination is slow relative to
      nelarabine and ara-G. In pediatric and adult patients, neurologic toxicity is
      dose limiting. Severe myelosuppression was not consistently observed. Major
      responses were seen in patients with T-cell malignancies. Patients who responded
      had significantly higher intracellular ara-GTP concentrations compared with those
      who did not respond. CONCLUSIONS: Nelarabine is an effective ara-G prodrug.
      Nelarabine has significant activity against malignant T-cells and appears to be
      an important addition to treatments of various leukemias.

PMID- 15870143
TI  - Timing of DAS28 in infliximab therapy.

PMID- 15870144
TI  - Fatal streptococcal toxic shock syndrome in a patient with rheumatoid arthritis
      treated with etanercept.

PMID- 15870145
TI  - Suboptimal physician adherence to quality indicators for the management of gout
      and asymptomatic hyperuricaemia: results from the UK General Practice Research
      Database (GPRD).
AB  - OBJECTIVES: : To examine adherence to validated quality indicators assessing the
      quality of allopurinol use in the treatment of gout and asymptomatic
      hyperuricaemia. METHODS: We determined physician adherence in the UK General
      Practice Research Database (GPRD) to three validated quality indicators developed
      to assess the quality of allopurinol prescribing practices. These indicators were
      developed to assess: (i) dosing in renal impairment; (ii) concomitant use with
      azathioprine or 6-mercaptopurine; and (iii) use in the treatment of asymptomatic
      hyperuricaemia. We also examined the association of patient-level factors
      (sociodemographics, comorbidity, follow-up duration and concomitant medicine use)
      with the treatment of asymptomatic hyperuricaemia using multivariable logistic
      regression. RESULTS: Of the 63 105 gout patients, 185 (0.3%) were eligible for
      Quality Indicator 1 and 52 (0.1%) were eligible for Quality Indicator 2. There
      were an additional 471 patients with asymptomatic hyperuricaemia eligible for
      Quality Indicator 3. Rates of practice deviation for the three individual quality
      indicators ranged from 25 to 57%. Male sex, older age, a history of chronic renal
      failure, and a greater number of concomitant medications were significantly
      associated with increased odds of inappropriate treatment for asymptomatic
      hyperuricaemia. Hypertension and diuretic use were associated with lower odds of
      this practice. CONCLUSIONS: One-quarter to one-half of all patients eligible for
      at least one of the validated quality of care indicators were subject to possible
      allopurinol prescribing error, suggesting that inappropriate prescribing
      practices are widespread with this agent. Future interventions aimed at reducing
      inappropriate allopurinol use are needed and should be targeted towards high-risk
      groups, including older men and those receiving multiple concomitant medications.

PMID- 15870147
TI  - Adalimumab-induced asthma.

PMID- 15870148
TI  - Association of apolipoprotein E polymorphism with bone mineral density in
      postmenopausal women with rheumatoid arthritis.

PMID- 15870149
TI  - Outcomes of total knee replacement: a qualitative study.
AB  - OBJECTIVE: To investigate patients' experiences of outcome from a total knee
      replacement (TKR). METHODS: In-depth interviews were conducted with 25 patients 3
      months before TKR, with 10 interviewed again 6 months after surgery. Patients
      were purposively sampled to include a range of demographic characteristics.
      Interviews were audiotaped and transcribed. Methods of constant comparison were
      used to analyse the data. RESULTS: Individuals struggled to make sense of their
      outcome and often described it in contradictory terms. When asked directly, most
      reported a good outcome, but further discussion revealed concern and discomfort
      with continuing pain and mobility difficulties. These apparently contradictory
      accounts were consistent with the presentation of public and private views, were
      dependent on the context of patients' lives, and represented an adaptation to
      their changed health state. CONCLUSION: Individuals reported their outcome from
      TKR as good despite the continued experience of pain and immobility. Although TKR
      has been shown to be a highly effective procedure using quantitative methods,
      they may need to be qualified by these qualitative findings.

PMID- 15870150
TI  - Adalimumab in clinical practice. Outcome in 70 rheumatoid arthritis patients,
      including comparison of patients with and without previous anti-TNF exposure.
AB  - OBJECTIVE: To assess the efficacy and safety of the fully human recombinant
      monoclonal anti-TNF antibody adalimumab in routine clinical practice, including
      comparison of patients with and without previous anti-TNF exposure. METHODS: We
      prospectively studied the outcome of 70 rheumatoid arthritis patients treated
      with adalimumab in normal clinical practice. The primary outcome measures were
      Disease Activity Score 28 (DAS28), EULAR (European League Against Rheumatism)
      response and Health Assessment Questionaire (HAQ). RESULTS: Seventy-seven per
      cent achieved a EULAR response (26% good, 51% moderate) and 19% were in
      remission. The mean decrease in DAS28 was 2.1 (6.3-4.2; P<0.001). The mean
      decrease in HAQ score was 0.34 (2.07-1.73; P<0.001), 66% achieving a clinically
      significant decrease of greater than 0.22. Twenty-three per cent stopped
      treatment because of side-effects (7%) or failure to respond (16%). Of the 26
      patients who had previously tried 29 biologicals, 65% responded to adalimumab.
      There was no significant difference in the change in mean DAS (P = 0.69) or HAQ
      (P = 0.88) between groups with and without previous anti-TNF exposure. Of the 13
      patients with previous secondary failure to infliximab, 77% responded to
      adalimumab. Patients with previous secondary failure had significantly better
      improvement in DAS (P = 0.023) than patients with previous primary failure.
      CONCLUSION: Our clinical experience confirms that adalimumab is effective and
      safe in the treatment of RA. It also shows adalimumab is effective in patients
      with previous biological failures, particularly patients with secondary failure
      to infliximab.

PMID- 15870151
TI  - Classification of systemic sclerosis. Visions and reality.
AB  - Systemic sclerosis, scleroderma (SSc) is a disabling condition that shortens life
      expectancy. Disease heterogeneity and difficulties separating SSc from SSc-like
      conditions make classification an important issue. Limited cutaneous and diffuse
      cutaneous SSc, with different severity and survival, have been recognized for
      several years as distinct subsets. Some authors have suggested an intermediate
      cutaneous form with intermediate survival. This issue remains unsettled, however.
      The technique of capillaroscopy is helpful as an adjunct diagnostic tool to
      separate idiopathic Raynaud's phenomenon from SSc. Digitized video-capillaroscopy
      is developing as a powerful new method to assess individual capillaries over
      time. Using the simpler techniques of video-capillaroscopy, different patterns
      have been described and named 'early', 'active', 'late' and 'slow'. The value of
      nailfold video-capillaroscopy to distinguish different subsets or provide
      prognostic information for use in daily practice remains to be assessed. The
      features of CREST (calcinosis, Raynaud's, oesophagus dysmotility, sclerodactyly,
      telangiectasias) are not confined to single subsets of SSc. There is no
      convincing evidence of any advantage for distinguishing the limited, intermediate
      and diffuse forms of SSc rather than only the limited and diffuse forms.

PMID- 15870152
TI  - Rheumatic fever--a vignette.

PMID- 15870153
TI  - Aberrant production of soluble costimulatory molecules CTLA-4, CD28, CD80 and
      CD86 in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: The costimulatory interactions of the B7 family molecules CD80 and
      CD86 on antigen-presenting cells with their T-cell counter-receptors CD28 and
      CTLA-4 modulate T lymphocyte-mediated immune responses in a reciprocal manner. We
      investigated the possible aberrant production of soluble (s) forms of the T-cell
      costimulatory molecules CD80, CD86, CD28 and CTLA-4 in plasma of patients with
      systemic lupus erythematosus (SLE), an autoimmune disease arising from T
      lymphocyte dysregulation. METHODS: Plasma concentration and ex vivo production of
      soluble costimulatory molecules of 79 SLE patients with or without active disease
      and 40 sex- and age-matched healthy subjects were measured by enzyme-linked
      immunosorbent assay. RESULTS: Plasma sCTLA-4, sCD28, sCD80 and sCD86
      concentrations of all SLE patients were significantly higher than concentrations
      in control subjects (all P<0.01). These increases were observed even in patients
      with inactive disease [SLE Disease Activity Index (SLEDAI) <3]. Plasma sCTLA-4
      concentration in all SLE patients correlated significantly with SLEDAI score (r =
      0.228, P = 0.043). Upon mitogen treatment of peripheral blood mononuclear cells,
      the percentage increases in ex vivo production of sCD28 and sCD80 and the
      percentage decrease in sCTLA-4 release were all significantly smaller in SLE
      patients with active disease than in healthy subjects (P<0.01, P<0.05 and
      P<0.0001, respectively). CONCLUSION: The aberrant production of soluble T-cell
      costimulatory molecules is important in the immunopathogenesis of SLE, which
      occurs by the dysregulation of T-lymphocyte costimulation. Plasma sCTLA
      concentration could potentially serve as a surrogate marker of SLE disease
      activity.

PMID- 15870154
TI  - Cytochrome P-450 1A1 gene polymorphisms and risk of breast cancer: a HuGE review.
AB  - Cytochrome P-450 (CYP) 1A1 plays a key role in phase I metabolism of polycyclic
      aromatic hydrocarbons and in estrogen metabolism. It is expressed predominantly
      in extrahepatic tissues, including the breast. Four CYP1A1 gene polymorphisms
      (3801T --> C, Ile462Val, 3205T --> C, and Thr461Asp) have been studied in
      relation to breast cancer. The 3801C variant is more common than the Val variant.
      Both variants occur more frequently in Asians than in White populations. The
      3205T --> C polymorphism has been observed in African Americans only. Little data
      are available on the geographic/ethnic distribution of the Thr461Asp
      polymorphism. The functional significance of the polymorphisms is unclear. In 17
      studies, no consistent association between breast cancer and CYP1A1 genotype was
      found. Meta-analysis found no significant risk for the genotypes 1) 3801C/C
      (relative risk (RR) = 0.97, 95% confidence interval (CI): 0.52, 1.80) or 3801T/C
      (RR = 0.91, 95% CI: 0.70, 1.19) versus 3801T/T, 2) Val/Val (RR = 1.04, 95% CI:
      0.63, 1.74) or Ile/Val (RR = 0.92, 95% CI: 0.76, 1.10) versus Ile/Ile, or 3)
      Asp/Asp (RR = 0.95, 95% CI: 0.20, 4.49) or Thr/Asp (RR = 1.12, 95% CI: 0.87,
      1.43) versus Thr/Thr. Future studies should explore possible interactions between
      CYP1A1 and sources of polycyclic aromatic hydrocarbons, markers of estrogen
      exposure, other lifestyle factors influencing hormonal levels, and other genes
      involved in polycyclic aromatic hydrocarbon metabolism or hormonal biosynthesis.

PMID- 15870155
TI  - Risk factors for autism: perinatal factors, parental psychiatric history, and
      socioeconomic status.
AB  - Research suggests that heredity and early fetal development play a causal role in
      autism. This case-control study explored the association between perinatal
      factors, parental psychiatric history, socioeconomic status, and risk of autism.
      The study was nested within a cohort of all children born in Denmark after 1972
      and at risk of being diagnosed with autism until December 1999. Prospectively
      recorded data were obtained from nationwide registries in Denmark. Cases totaled
      698 children with a diagnosis of autism; each case was individually matched by
      gender, birth year, and age to 25 controls. Analyses by conditional logistic
      regression produced risk ratios and 95% confidence intervals. Adjusted analyses
      showed that the risk of autism was associated with breech presentation (risk
      ratio (RR) = 1.63, 95% confidence interval (CI): 1.18, 2.26), low Apgar score at
      5 minutes (RR = 1.89, 95% CI: 1.10, 3.27), gestational age at birth <35 weeks (RR
      = 2.45, 95% CI: 1.55, 3.86), and parental psychiatric history (schizophrenia-like
      psychosis: RR = 3.44, 95% CI: 1.48, 7.95; affective disorder: RR = 2.91, 95% CI:
      1.65, 5.14). Analyses showed no statistically significant association between
      risk of autism and weight for gestational age, parity, number of antenatal
      visits, parental age, or socioeconomic status. Results suggest that prenatal
      environmental factors and parental psychopathology are associated with the risk
      of autism. These factors seem to act independently.

PMID- 15870157
TI  - History of chickenpox and shingles and prevalence of antibodies to varicella
      zoster virus and three other herpesviruses among adults with glioma and controls.
AB  - Whether viruses or immunologic factors might cause or prevent human brain cancer
      is of interest. Statistically significant inverse associations of adult glioma
      with history of chickenpox and immunoglobulin G antibodies to varicella-zoster
      virus have been reported. The authors evaluate associations of immunoglobulin G
      antibodies to varicella-zoster virus and three other herpesviruses among 229
      adults with glioma and 289 controls in the San Francisco Bay Area Adult Glioma
      Study (1997-2000). Cases were less likely than controls to report a history of
      chickenpox (for self-reported cases vs. controls: the age-, gender-, and
      ethnicity-adjusted odds ratio = 0.59, 95% confidence interval: 0.40, 0.86), and
      they also had lower levels of immunoglobulin G to varicella-zoster virus (for
      being in the highest quartile vs. the lowest quartile: the age-, gender-, and
      ethnicity-adjusted odds ratio = 0.41, 95% confidence interval: 0.24, 0.70). The
      inverse association with anti-varicella-zoster virus immunoglobulin G was most
      marked for glioblastoma multiforme cases versus controls and was only somewhat
      attenuated by excluding subjects taking high-dose steroids and other medications.
      Cases and controls did not differ notably for positivity to three other
      herpesviruses, Epstein-Barr virus, cytomegalovirus, and herpes simplex virus.
      Cohort studies may help to clarify the nature of the association between immunity
      to and/or clinical manifestations of varicella-zoster virus and glioblastoma.

PMID- 15870158
TI  - Effect of adiposity and fat distribution on endometrial cancer risk in Shanghai
      women.
AB  - The authors conducted a population-based case-control study of 832 endometrial
      cancer cases and 846 frequency-matched controls in Shanghai, China (1997-2001),
      to examine the association of overall adiposity and body fat distribution with
      disease risk. Overall adiposity was estimated using weight and body mass index
      (BMI); upper body fat distribution was evaluated using waist circumference and
      waist:hip ratio. Overall and upper-body obesity were both associated with an
      elevated risk of endometrial cancer. Adjusted odds ratios and 95% confidence
      intervals for highest-versus-lowest quartile comparisons were 2.6 (95% confidence
      interval (CI): 2.0, 3.5) for weight, 2.9 (95% CI: 2.2, 3.9) for BMI, 4.7 (95% CI:
      3.4, 6.4) for waist circumference, and 3.5 (95% CI: 2.6, 4.8) for waist:hip
      ratio. The positive associations with weight and BMI vanished after results were
      controlled for waist circumference, while associations with waist circumference
      and waist:hip ratio persisted after adjustment for BMI. The positive association
      with upper-body obesity was more pronounced among younger women, women who had
      never used oral contraceptives, and women with a history of diabetes mellitus (p
      for multiplicative interaction < 0.05). Upper-body obesity was related to
      increased risk among women with low BMI. These results suggest that obesity,
      particularly upper-body fat deposition, is associated with an increased risk of
      endometrial cancer.

PMID- 15870159
TI  - Prospective study of dietary fat and risk of cataract extraction among US women.
AB  - The authors examined prospectively the association between dietary fat intake and
      cataract extraction in adult women from the Nurses' Health Study. A total of
      71,083 women were followed prospectively for up to 16 years between 1984 and
      2000. Dietary fat was assessed by repeated food frequency questionnaires.
      Incident cases of cataract extraction were determined by a biennial
      questionnaire. The multivariate-adjusted relative risk for the highest compared
      with the lowest quintile of total fat intake was 1.10 (95% confidence interval
      (CI): 0.99, 1.22; p(trend) = 0.01). Women in the highest quintile of long-chain
      omega-3 fatty acid had a 12% lower risk of cataract extraction compared with
      those in the lowest quintile (relative risk = 0.88, 95% CI: 0.79, 0.98; p(trend)
      = 0.02). Total fish intake was inversely associated with cataract (for intake of
      > or = 3/week vs. <1/month: relative risk = 0.89, 95% CI: 0.81, 0.98; p(trend) =
      0.01). The authors' findings suggest that higher intake of long-chain omega-3
      fatty acid (eicosapentaenoic acid and docosahexaenoic acid) and consumption of
      fish may modestly reduce the risk of cataract.

PMID- 15870160
TI  - Social network diversity and risks of ischemic heart disease and total mortality:
      findings from the Copenhagen City Heart Study.
AB  - Measures of various types of social contacts were used as predictors of ischemic
      heart disease events and total mortality in an age-stratified random sample of
      9,573 adults enrolled in the Copenhagen City Heart Study (Copenhagen, Denmark).
      Baseline examinations were conducted in 1991-1994, and participants were followed
      until the end of 1997. Contacts with parents, children, family members, and
      friends were associated with better health. The presence of a spouse or partner
      was protective for men. Contacts with neighbors showed a trend toward a reversed
      pattern, and the effects of contacts with work colleagues and children differed
      by gender. Most types of contacts that occurred at least monthly were just as
      protective as those occurring more frequently. An index of intimate social
      contact diversity with family and friends had graded relations with both
      outcomes. Comparisons of persons reporting three or more types of contacts with
      those reporting fewer types yielded age- and gender-adjusted hazard ratios of
      0.73 (95% confidence interval (CI): 0.64, 0.82) for mortality and 0.75 (95% CI:
      0.61, 0.91) for ischemic heart disease. Comparable fully adjusted hazard ratios
      were 0.83 (95% CI: 0.73, 0.95) and 0.82 (95% CI: 0.67, 1.00). These data suggest
      that health benefits are derived from the diversity of social roles, especially
      those involving intimate relationships.

PMID- 15870161
TI  - Relation between blood lead levels and childhood anemia in India.
AB  - Lead pollution is a substantial problem in developing countries such as India.
      The US Centers for Disease Control and Prevention has defined an elevated blood
      lead level in children as > or = 10 microg/dl, on the basis of neurologic
      toxicity. The US Environmental Protection Agency suggests a threshold lead level
      of 20-40 microg/dl for risk of childhood anemia, but there is little information
      relating lead levels <40 microg/dl to anemia. Therefore, the authors examined the
      association between lead levels as low as 10 mug/dl and anemia in Indian children
      under 3 years of age. Anemia was divided into categories of mild (hemoglobin
      level 10-10.9 g/dl), moderate (hemoglobin level 8-9.9 g/dl), and severe
      (hemoglobin level <8 g/dl). Lead levels <10 mug/dl were detected in 568 children
      (53%), whereas 413 (38%) had lead levels > or = 10-19.9 microg/dl and 97 (9%) had
      levels > or = 20 microg/dl. After adjustment for child's age, duration of
      breastfeeding, standard of living, parent's education, father's occupation,
      maternal anemia, and number of children in the immediate family, children with
      lead levels > or = 10 microg/dl were 1.3 (95% confidence interval: 1.0, 1.7)
      times as likely to have moderate anemia as children with lead levels <10
      microg/dl. Similarly, the odds ratio for severe anemia was 1.7 (95% confidence
      interval: 1.1, 2.6). Health agencies in India should note the association of
      elevated blood lead levels with anemia and make further efforts to curb lead
      pollution and childhood anemia.

PMID- 15870162
TI  - Interrater reliability: completing the methods description in medical records
      review studies.
AB  - In medical records review studies, information on the interrater reliability
      (IRR) of the data is seldom reported. This study assesses the IRR of data
      collected for a complex medical records review study. Elements selected for
      determining IRR included "demographic" data that require copying explicit
      information (e.g., gender, birth date), "free-text" data that require identifying
      and copying (e.g., chief complaints and diagnoses), and data that require
      abstractor judgment in determining what to record (e.g., whether heart disease
      was considered). Rates of agreement were assessed by the greatest number of
      answers (one to all n) that were the same. The IRR scores improved over time. At
      1 month, the reliability for demographic data elements was very good, for free
      text data elements was good, but for data elements requiring abstractor judgment
      was unacceptable (only 3.4 of six answers agreed, on average). All assessments
      after 6 months showed very good to excellent IRR. This study demonstrates that
      IRR can be evaluated and summarized, providing important information to the study
      investigators and to the consumer for assessing the reliability of the data and
      therefore the validity of the study results and conclusions. IRR information
      should be required for all large medical records studies.

PMID- 15870163
TI  - Validity of self-reported causes of subfertility.
AB  - The authors assessed the accuracy of cause(s) of subfertility as reported by
      women in a self-administered questionnaire in comparison with medical record
      information, in a nationwide cohort study of women receiving in vitro
      fertilization treatment in the Netherlands (n = 9,164) between 1983 and 1995.
      Validity was expressed as sensitivity and specificity, and reliability was
      expressed by the kappa statistic and overall agreement between self-reports and
      medical records for various subfertility categories. The sensitivity for
      subfertility attributed to tubal, male, hormonal, cervical, uterine, and
      idiopathic factors and for endometriosis was 84%, 78%, 65%, 40%, 46%, 59%, and
      83%, respectively. The corresponding kappas were 0.79, 0.71, 0.38, 0.34, 0.13,
      0.50, and 0.52, respectively. For 54% of all women who reported two or more
      causes of subfertility, the medical record revealed only one major factor.
      Conversely, for 43% of all women whose subfertility was attributed to two or more
      major factors in the record, only one factor was reported by the women. Older age
      at the time of filling out the questionnaire, low educational level, long
      duration of subfertility, and pre-in vitro fertilization treatment were
      associated with less accurate reporting. The results indicate that the validity
      of self-reports for tubal and male subfertility is satisfactory. For unexplained
      subfertility, the validity is moderate; for other causes of subfertility and when
      two causes of subfertility play a role, the validity is low.

PMID- 15870164
TI  - Measurement of fruit and vegetable consumption with diet questionnaires and
      implications for analyses and interpretation.
AB  - Measurement error can have an important impact on the estimation of the true
      relation between diet and disease. The authors examined the performance of models
      regressing plasma vitamin C level on fruit and vegetable consumption and the
      effect of categorization of fruit and vegetable consumption on the association
      with plasma vitamin C. They used diet information reported by 4,487 participants
      in the Norfolk, United Kingdom, portion of the European Prospective Investigation
      into Cancer and Nutrition by means of a 7-day diet diary and a food frequency
      questionnaire (FFQ) (1993-1998). The authors found substantial differences in
      mean fruit and vegetable consumption assessed by the two diet instruments.
      Consumption estimated with the FFQ was about twice as high as that obtained with
      the 7-day diary, and the ranking of individuals according to estimates of fruit
      and vegetable consumption from the 7-day diary and the FFQ differed
      substantially. When fruit and vegetable consumption were categorized into
      quintiles, the two questionnaires produced similar associations of relative
      intake with plasma vitamin C, but estimation of the association of absolute
      intake with plasma vitamin C differed.

PMID- 15870165
TI  - Re: "Carbohydrate intake, glycemic index, glycemic load, and dietary fiber in
      relation to risk of stroke in women".

PMID- 15870166
TI  - INTERALIGN: interactive alignment editor for distantly related protein sequences.
AB  - SUMMARY: Improving and ascertaining the quality of a multiple sequence alignment
      is a very challenging step in protein sequence analysis. This is particularly the
      case when dealing with sequences in the 'twilight zone', i.e. sharing < 30%
      identity. Here we describe INTERALIGN, a dedicated user-friendly alignment editor
      including a view of secondary structures and a synchronized display of carbon
      alpha traces of corresponding protein structures. Profile alignment, using
      CLUSTALW, is implemented to improve the alignment of a sequence of unknown
      structure with the visually optimized structural alignment as compared with a
      standard multiple sequence alignment. Tree-based ordering further helps in
      identifying the structure closest to a given sequence.

PMID- 15870167
TI  - DIG--a system for gene annotation and functional discovery.
AB  - SUMMARY: We describe a database and information discovery system named DIG (Duke
      Integrated Genomics) designed to facilitate the process of gene annotation and
      the discovery of functional context. The DIG system collects and organizes gene
      annotation and functional information, and includes tools that support an
      understanding of genes in a functional context by providing a framework for
      integrating and visualizing gene expression, protein interaction and literature
      based interaction networks.

PMID- 15870168
TI  - Enhanced statistics for local alignment of multiple alignments improves
      prediction of protein function and structure.
AB  - MOTIVATION: Improved comparisons of multiple sequence alignments (profiles) with
      other profiles can identify subtle relationships between protein families and
      motifs significantly beyond the resolution of sequence-based comparisons.
      RESULTS: The local alignment of multiple alignments (LAMA) method was modified to
      estimate alignment score significance by applying a new measure based on Fisher's
      combining method. To verify the new procedure, we used known protein structures,
      sequence annotations and cyclical relations consistency analysis (CYRCA) sets of
      consistently aligned blocks. Using the new significance measure improved the
      sensitivity of LAMA without altering its selectivity. The program performed
      better than other profile-to-profile methods (COMPASS and Prof_sim) and a
      sequence-to-profile method (PSI-BLAST). The testing was large scale and used
      several parameters, including pseudo-counts profile calculations and local
      ungapped blocks or more extended gapped profiles. This comparison provides
      guidelines to the relative advantages of each method for different cases. We
      demonstrate and discuss the unique advantages of using block multiple alignments
      of protein motifs.

PMID- 15870169
TI  - The serotonin transporter (SLC6A4) is present in B-cell clones of diverse
      malignant origin: probing a potential anti-tumor target for psychotropics.
AB  - Following our previous description of the serotonin transporter (SERT) acting as
      a conduit to 5-hydroxytryptamine (5-HT)-mediated apoptosis, specifically in
      Burkitt's lymphoma, we now detail its expression among a broad spectrum of B cell
      malignancy, while exploring additional SERT substrates for potential therapeutic
      activity. SERT was readily detected in derived B cell lines with origins as
      diverse as B cell precursor acute lymphoblastic leukemia, mantle cell lymphoma,
      diffuse large B cell lymphoma, and multiple myeloma. Concentration and timecourse
      kinetics for the antiproliferative and proapoptotic activities of the amphetamine
      derivatives fenfluramine (an appetite suppressant) and 3,4
      methylenedioxymethamphetamine (MDMA; "Ecstasy") revealed them as being similar to
      the endogenous indoleamine. A tricyclic antidepressant, clomipramine, instead
      mirrored the behavior of the selective serotonin reuptake inhibitor fluoxetine,
      both being effective in the low micromolar range. A majority of neoplastic clones
      were sensitive to one or more of the serotonergic compounds. Dysregulated bcl-2
      expression, either by t(14;18)(q32;q21) translocation or its introduction as a
      constitutively active transgene, provided protection from proapoptotic but not
      antiproliferative outcomes. These data indicate a potential for SERT as a novel
      anti-tumor target for amphetamine analogs, while evidence is presented that the
      seemingly more promising antidepressants are likely impacting malignant B cells
      independently of the transporter itself.

PMID- 15870170
TI  - Nitric oxide synthase distribution and expression with ischemic preconditioning
      of the rat liver.
AB  - This study was undertaken to identify nitric oxide synthase (NOS) isoforms
      responsible for the generation of cytoprotective NO during liver ischemic
      preconditioning (IPC). Sprague-Dawley rats were subjected to 45 min lobar
      ischemia followed by 2 h reperfusion. L-arginine or Nomega-nitro-L-arginine
      methyl ester (L-NAME) was administered to stimulate or block NO synthesis. Study
      groups (n=6) had 1) sham laparotomy, 2) ischemia reperfusion (IR), 3) IPC with 5
      min ischemia and 10 min reperfusion before IR, 4) L-arginine before IR, or 5) L
      NAME + IPC before IR. Liver function tests, nitrite + nitrate (NOx) and plasma
      amino acids were analyzed. The endothelial cell and inducible isoforms of NOS
      (eNOS and iNOS) were identified using immunohistochemistry and Western blotting.
      Both IPC and L-arginine treatment increased NOx (P<0.05) and improved serum liver
      enzymes (P<0.05) when compared with IR. These effects were prevented by L-NAME.
      Hepatic vein NOx was significantly higher than circulating NOx. iNOS expression
      was absent within the groups. The preconditioned livers were associated with up
      regulation of eNOS expression and also increased L-arginine levels. The effects
      of L-arginine administration were similar to those evident following IPC. Thus,
      cytoprotective NO generation during IPC of the liver was a result of increased
      eNOS expression and increased L-arginine substrate availability.

PMID- 15870172
TI  - Nucleophosmin mutations in childhood acute myelogenous leukemia with normal
      karyotype.
AB  - Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein involved in leukemia
      associated chromosomal translocations, and it regulates the alternate reading
      frame (ARF)-p53 tumor-suppressor pathway. Recently, it has been demonstrated that
      mutations of the NPM1 gene alter the protein at its C-terminal, causing its
      cytoplasmic localization. Cytoplasmic NPM was detected in 35% of adult patients
      with primary non-French-American-British (FAB) classification M3 acute myeloid
      leukemia (AML), associated mainly with normal karyotype. We evaluated the
      prevalence of the NPM1 gene mutation in non-M3 childhood AML patients enrolled in
      the ongoing Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP
      AML02) protocol in Italy. NPM1 mutations were found in 7 (6.5%) of 107
      successfully analyzed patients. NPM1-mutated patients carried a normal karyotype
      (7/26, 27.1%) and were older in age. Thus, the NPM1 mutation is a frequent
      abnormality in AML patients without known genetic marker; the mutation may
      represent a new target to monitor minimal residual disease in AML and a potential
      candidate for alternative and targeted treatments.

PMID- 15870171
TI  - A novel stem-cell population in adult liver with potent hematopoietic
      reconstitution activity.
AB  - A number of recent reports have documented that cells possessing hematopoietic
      reconstitution ability can be identified and isolated from a variety of solid
      organs in the adult animal. In all studies to date, however, purified organ
      derived stem cells demonstrate a diminished repopulating capacity relative to
      that of purified bone marrow-derived hematopoietic stem cells (BM HSCs). It has
      therefore been unclear whether organ-derived HSCs possess functional properties
      distinct from those of BM HSCs, or simply have not been purified to a comparable
      extent. Here we report the identification of a rare subset of cells in adult
      murine liver that possess potent blood-repopulating potential, approaching that
      of BM HSCs. The cells, isolated on the basis of dye-efflux activity and CD45
      expression (termed CD45(+) liver side population [SP] tip cells), exhibit a
      surface phenotype similar to that of freshly isolated BM HSCs derived from normal
      adult animals, but are phenotypically distinct in that they do not express the
      stem-cell marker c-kit. Single-cell transplantation studies indicate that CD45(+)
      liver SP tip cells can be generated from BM HSCs, suggesting a relationship
      between stem-cell populations in the liver and bone marrow compartments. Overall,
      these studies have important implications for understanding extramedullary
      hematopoiesis, and may be relevant to current strategies aimed at inducing
      tolerance to transplanted organs.

PMID- 15870173
TI  - Life-threatening nonspherocytic hemolytic anemia in a patient with a null
      mutation in the PKLR gene and no compensatory PKM gene expression.
AB  - Human erythrocyte R-type pyruvate kinase (RPK) deficiency is an autosomal
      recessive disorder produced by mutations in the PKLR gene, causing chronic
      nonspherocytic hemolytic anemia. Survival of patients with severe RPK deficiency
      has been associated with compensatory expression in red blood cells (RBCs) of
      M2PK, an isoenzyme showing wide tissue distribution. We describe a novel
      homozygous null mutation of the PKLR gene found in a girl with a prenatal
      diagnosis of PK deficiency. The mutant PK gene revealed an 11-nucleotide (nt)
      duplication at exon 8, causing frameshift of the PKLR transcript, predicting a
      truncated protein inferred to have no catalytic activity. Western blot analysis
      and quantitative reverse transcription-polymerase chain reaction (qRT-PCR)
      detected no M2PK expression in the peripheral blood red cell fraction. The
      expression of mutant RPK mRNA in the RBCs was almost 6 times higher than that
      detected in a control patient with hereditary spherocytosis. This molecular
      phenotypic analysis of the null mutation in the PKLR gene provides evidence for a
      lack of M2PK in the mature RBCs of this patient and suggests that normal red cell
      functions and survival are achieved through a population of young erythroid cells
      released into the circulation in response to anemia.

PMID- 15870174
TI  - 2B4 (CD244)-CD48 interactions provide a novel MHC class I-independent system for
      NK-cell self-tolerance in mice.
AB  - Natural killer (NK) cells must be able to eliminate infected and transformed
      cells while remaining tolerant of normal cells. NK-cell self-tolerance is thought
      to be maintained by self-major histocompatibility complex (MHC) class I
      recognition; however, there are examples where NK cells are not regulated by MHC
      class I and yet remain self-tolerant. Here, we show that 2B4 (CD244) and CD48
      represent a second system for murine NK-cell self-recognition. 2B4 and MHC class
      I receptors act nonredundantly to inhibit NK lysis of syngeneic tumor cells. NK
      cells from beta2 microglobulin (beta2m)-deficient mice and NK cells that lack
      expression of self-MHC-binding inhibitory receptors are inhibited by 2B4.
      Moreover, we provide the first in vivo evidence for MHC-independent NK self
      recognition in a bone marrow rejection assay. These data suggest that NK-cell
      self-tolerance can be mediated by molecules other than MHC.

PMID- 15870175
TI  - Honokiol overcomes conventional drug resistance in human multiple myeloma by
      induction of caspase-dependent and -independent apoptosis.
AB  - Honokiol (HNK) is an active component purified from magnolia, a plant used in
      traditional Chinese and Japanese medicine. Here we show that HNK significantly
      induces cytotoxicity in human multiple myeloma (MM) cell lines and tumor cells
      from patients with relapsed refractory MM. Neither coculture with bone marrow
      stromal cells nor cytokines (interleukin-6 and insulin-like growth factor-1)
      protect against HNK-induced cytotoxicity. Although activation of caspases 3, 7,
      8, and 9 is triggered by HNK, the pan-caspase inhibitor z-VAD-fmk does not
      abrogate HNK-induced apoptosis. Importantly, release of an executioner of caspase
      independent apoptosis, apoptosis-inducing factor (AIF), from mitochondria is
      induced by HNK treatment. HNK induces apoptosis in the SU-DHL4 cell line, which
      has low levels of caspase 3 and 8 associated with resistance to both conventional
      and novel drugs. These results suggest that HNK induces apoptosis via both
      caspase-dependent and -independent pathways. Furthermore, HNK enhances MM cell
      cytotoxicity and apoptosis induced by bortezomib. In addition to its direct
      cytotoxicity to MM cells, HNK also represses tube formation by endothelial cells,
      suggesting that HNK inhibits neovascurization in the bone marrow
      microenvironment. Taken together, our results provide the preclinical rationale
      for clinical protocols of HNK to improve patient outcome in MM.

PMID- 15870176
TI  - Critical variables in the conversion of marrow cells to skeletal muscle.
AB  - We have studied conversion of marrow cells to skeletal muscle in cardiotoxin
      injured anterior tibialis muscle in a green fluorescent protein (GFP) to C57BL/6
      transplantation model and ascertained that total body irradiation (TBI) with
      establishment of chimerism is a critical factor. Local irradiation has little
      effect in lower doses and was detrimental at higher doses. Whole body (1000 cGy)
      with shielding of the leg or a combination of 500 cGy TBI and 500 cGy local
      radiations was found to give the best results. In non-obese diabetic-severe
      combined immunodeficient (NOD-SCID) recipients, we were able to show that
      conversion could occur without radiation, albeit at relatively lower levels.
      Within 3 days of cardiotoxin injury, GFP-positive mononuclear cells were seen in
      the muscle, and within 2 weeks GFP-positive muscle fibers were identified.
      Conversion rates were increased by increasing donor-cell dose. Timing of the
      cardiotoxin injury relative to the transplantation was critical. These studies
      show that variables in transplantation and injury are critical features of marrow
      to-muscle conversions. Irradiation primarily effects conversion by promoting
      chimerism. These data may explain the differences in the literature for the
      frequency of marrow-to-skeletal muscle conversion and can set a platform for
      future models and perhaps clinical protocols.

PMID- 15870177
TI  - NFkappaB activity, function, and target-gene signatures in primary mediastinal
      large B-cell lymphoma and diffuse large B-cell lymphoma subtypes.
AB  - Primary mediastinal large B-cell lymphoma (MLBCL) shares important clinical and
      molecular features with classic Hodgkin lymphoma, including nuclear localization
      of the nuclear factor kappaB (NFkappaB) subunit c-REL (reticuloendotheliosis
      viral oncogene homolog) in a pilot series. Herein, we analyzed c-REL subcellular
      localization in additional primary MLBCLs and characterized NFkappaB activity and
      function in a MLBCL cell line. The new primary MLBCLs had prominent c-REL nuclear
      staining, and the MLBCL cell line exhibited high levels of NFkappaB binding
      activity. MLBCL cells expressing a superrepressor form of inhibitor of kappa B
      alpha signaling (IkappaB alpha) had a markedly higher rate of apoptosis,
      implicating constitutive NFkappaB activity in MLBCL cell survival. The
      transcriptional profiles of newly diagnosed primary MLBCLs and diffuse large B
      cell lymphomas (DLBCLs) were then used to characterize the NFkappaB target gene
      signatures of MLBCL and specific DLBCL subtypes. MLBCLs expressed increased
      levels of NFkappaB targets that promote cell survival and favor antiapoptotic
      tumor necrosis factor alpha (TNFalpha) signaling. In contrast, activated B cell
      (ABC)-like DLBCLs had a more restricted, potentially developmentally regulated,
      NFkappaB target gene signature. Of interest, the newly characterized host
      response DLBCL subtype had a robust NFkappaB target gene signature that partially
      overlapped that of primary MLBCL. In this large series of primary MLBCLs and
      DLBCLs, NFkappaB activation was not associated with amplification of the cREL
      locus, suggesting alternative pathogenetic mechanisms.

PMID- 15870178
TI  - Genetic influences on peripheral blood cell counts: a study in baboons.
AB  - Interperson differences in peripheral blood cell counts in healthy individuals
      result from genetic and environmental influences. We used multivariate genetic
      analyses to assess the relative impact of genes and environment on baseline blood
      cell counts and indices using a pedigreed colony of baboons, an animal with well
      documented analogies to human blood physiology. After accounting for age, sex,
      and weight, we found that genetic influences explain a significant proportion of
      the remaining variability, ranging from a low of 13.7% for mean corpuscular
      hemoglobin concentration (MCHC) to a high of 72.4% for red blood cell (RBC)
      number. Genes influence 38.5% of the variation in baseline white blood cell (WBC)
      count, a characteristic that correlates with mortality in both the general human
      population and clinically defined subgroups such as individuals with sickle-cell
      disease. We examined the interaction between pairs of traits and identified those
      that share common genetic influences (pleiotropy). We unexpectedly observed that
      the same gene or group of genes influences both WBC count and mean platelet
      volume (MPV). We anticipate that this approach will ultimately lead to discovery
      of novel insights into the biology of related traits, and ultimately identify
      important genes that affect hematopoiesis.

PMID- 15870179
TI  - The influence of high-altitude living on body iron.
AB  - The quantitative assessment of body iron based on measurements of the serum
      ferritin and transferrin receptor was used to examine iron status in 800 Bolivian
      mothers and one of their children younger than 5 years. The survey included
      populations living at altitudes between 156 to 3750 m. Body iron stores in the
      mothers averaged 3.88 +/- 4.31 mg/kg (mean +/- 1 SD) and 1.72 +/- 4.53 mg/kg in
      children. No consistent effect of altitude on body iron was detected in children
      but body iron stores of 2.77 +/- 0.70 mg/kg (mean +/- 2 standard error [SE]) in
      women living above 3000 m was reduced by one-third compared with women living at
      lower altitudes (P < .001). One half of the children younger than 2 years were
      iron deficient, but iron stores then increased linearly to approach values in
      their mothers by 4 years of age. When body iron in mothers was compared with that
      of their children, a striking correlation was observed over the entire spectrum
      of maternal iron status (r = 0.61, P < .001). This finding could provide the
      strongest evidence to date of the importance of dietary iron as a determinant of
      iron status in vulnerable segments of a population.

PMID- 15870180
TI  - High-dose chemotherapy and autologous stem cell transplantation for primary
      refractory or relapsed Hodgkin lymphoma: long-term outcome in the first 100
      patients treated in Vancouver.
AB  - Beginning in 1985, patients in British Columbia with Hodgkin lymphoma (HL) that
      was not controlled by conventional chemotherapy routinely underwent high-dose
      chemotherapy and autologous stem cell transplantation (HD-ASCT). Long-term
      complications of HD-ASCT have become apparent as more patients survive without
      recurrence of HL. Data were obtained retrospectively on the first 100 patients
      that underwent HD-ASCT for HL in Vancouver, focusing on relapse, treatment
      related complications, and the occurrence of late events. Fifty-three patients
      remain alive (median follow-up, 11.4 years [range, 10.0-17.4 years]) with an
      overall survival (OAS) of 54% at 15 years. OAS was significantly better in
      patients in first relapse (67%) than in patients with primary refractory
      induction failure (39%) and advanced disease (29%) (P = .002). The major cause of
      death was progression of HL (32% at 15 years). Treatment-related mortality,
      including death from second malignancy, was 17% at 15 years. Cumulative risk of a
      second malignancy was 9% at 15 years. Karnofsky performance status was at least
      90% in 47 patients although hypogonadism (20 patients), hypothyroidism (12
      patients), unusual infections (10 patients), anxiety or depression (7 patients),
      and cardiac disease (5 patients) were not uncommon in survivors. HD-ASCT can lead
      to durable remissions in relapsed or refractory HL with acceptable but definite
      late toxicity. The occurrence of late events necessitates lifelong medical
      surveillance.

PMID- 15870181
TI  - Haploinsufficiency, rather than the effect of an excessive production of soluble
      CD95 (CD95{Delta}TM), is the basis for ALPS Ia in a family with duplicated 3'
      splice site AG in CD95 intron 5 on one allele.
AB  - Autoimmune lymphoproliferative syndrome type Ia (ALPS Ia) is caused by mutations
      in the CD95/APO1/FAS (TN-FRSF6) gene, which lead to a defective CD95 ligand
      (CD95L)-induced apoptosis. Soluble CD95 (sCD95) has been suggested to play an
      important role in the pathogenesis of diverse autoimmune and malignant diseases
      by antagonizing CD95L. Here we evaluate a family with 4 of its 5 members
      harboring an ex-6-3C-->G mutation that affects the splice cis regulatory region
      (cctacag/ex-6-->cctagag/ex-6) of the CD95 gene. The mutation causes skipping of
      exon-6, which encodes the transmembrane region of CD95, and thereby leads to an
      excessive production of sCD95 in all 4 affected individuals. The mutation is
      associated with a low penetrance of disease phenotype and caused mild and
      transient ALPS in one male patient whereas all other family members are
      completely healthy. In all family members with the mutation we found that the
      cell surface expression of CD95 was low and the activated T cells were resistant
      to CD95-induced apoptosis. Unexpectedly, excessive production or addition of
      sCD95 had no effect on the CD95-induced apoptosis in diverse cells. In contrast,
      increasing the surface expression of CD95 was able to correct the defect in
      apoptosis. Thus we conclude that the ALPS in the one male patient was caused by
      haploinsufficiency of membrane CD95 expression. Our data challenge the hypothesis
      that sCD95 causes autoimmunity.

PMID- 15870182
TI  - Antiphospholipid syndrome in patients with systemic lupus erythematosus treated
      by autologous hematopoietic stem cell transplantation.
AB  - Systemic lupus erythematosus (SLE) is the most common disease associated with
      antiphospholipid syndrome (APS). We, therefore, evaluated 46 patients with
      refractory SLE treated by autologous hematopoietic stem cell transplantation
      (HSCT) for a history of APS prior to transplantation. The prevalence of SLE
      related APS in our patient population was 61% (28 of 46 patients with refractory
      SLE). Nineteen of 28 patients with APS had lupus anticoagulant (LA) or high
      titers of anticardiolipin antibodies (ACLAs), either immunoglobulin (Ig)G or IgM,
      when evaluated at study entry. Six of 8 evaluable LA+ patients became and
      remained LA-; 5 of 7 initially ACLA IgG+ patients and 9 of 11 ACLA IgM+ patients
      demonstrated normalization of ACLA titers when followed after HSCT. Eighteen of
      22 patients refractory to chronic anticoagulation discontinued anticoagulation
      therapy a median of 4 months after transplantation; 78% of them remained free of
      thrombotic events and in complete SLE remission for up to 78 months (median, 15
      months) after HSCT. There was no treatment-related mortality. Autologous HSCT may
      be performed safely in patients with APS and appears to be effective therapy for
      eliminating ALPAs and preventing thrombotic complications in patients with SLE.

PMID- 15870183
TI  - Drug therapy for acute myeloid leukemia.
AB  - Although improvement in outcomes has occurred in younger adults with acute
      myeloid leukemia (AML) during the past 4 decades, progress in older adults has
      been much less conspicuous, if at all. Approximately 50% to 75% of adults with
      AML achieve complete remission (CR) with cytarabine and an anthracycline such as
      daunorubicin or idarubicin or the anthracenedione mitoxantrone. However, only
      approximately 20% to 30% of the patients enjoy long-term disease survival.
      Various postremission strategies have been explored to eliminate minimal residual
      disease. The optimal dose, schedule, and number of cycles of postremission
      chemotherapy for most patients are not known. A variety of prognostic factors can
      predict outcome and include the karyotype of the leukemic cells and the presence
      of transmembrane transporter proteins, which extrude certain chemotherapy agents
      from the cell and confer multidrug resistance and mutations in or over
      expressions of specific genes such as WT1, CEBPA, BAX and the ratio of BCL2 to
      BAX, BAALC, EVI1, KIT, and FLT3. Most recently, insights into the molecular
      pathogenesis of AML have led to the development of more specific targeted agents
      and have ushered in an exciting new era of antileukemia therapy. Such agents
      include the immunoconjugate gemtuzumab ozogamicin, multidrug resistance
      inhibitors, farnesyl transferase inhibitors, histone deacetylase and proteosome
      inhibitors, antiangiogenesis agents, Fms-like tyrosine kinase 3 (FLT3)
      inhibitors, and apoptosis inhibitors.

PMID- 15870184
TI  - The S1P-analog FTY720 differentially modulates T-cell homing via HEV: T-cell
      expressed S1P1 amplifies integrin activation in peripheral lymph nodes but not in
      Peyer patches.
AB  - Sphingosine-1-phosphate (S1P) and its receptor S1P1 control T-cell egress from
      thymus and secondary lymphoid organs (SLOs). To further define the role of S1P1
      in lymphocyte trafficking, we performed adoptive transfer experiments and
      intravital microscopy (IVM) using both S1P1-/- lymphocytes and recipient wild
      type (WT) mice treated with FTY720, an immunosuppressant that downmodulates S1P
      receptors. S1P1 deficiency and FTY720 caused rapid disappearance of T cells from
      blood, prolonged retention in SLOs, and accumulation in bone marrow, but did not
      alter interstitial T-cell motility in peripheral lymph nodes (PLNs) as assessed
      by multiphoton IVM. However, S1P1-/- lymphocytes displayed reduced short-term
      homing to PLNs due to attenuated integrin-mediated firm arrest in high
      endothelial venules (HEVs). By contrast, S1P1-/- T cells homed normally to Peyer
      patches (PPs), whereas S1P1-/- B cells had a marked defect in homing to PPs and
      arrested poorly in PP HEVs. Therefore, S1P1 not only controls lymphocyte egress
      from SLOs, but also facilitates in a tissue- and subset-specific fashion integrin
      activation during homing. Interestingly, FTY720 treatment enhanced accumulation
      of both S1P1 sufficient and S1P1-/- T cells in PPs by enhancing integrin-mediated
      arrest in HEVs. Thus, FTY720 exerts unique effects on T-cell traffic in PPs that
      are independent of T-cell-expressed S1P1.

PMID- 15870186
TI  - Polyclonality of familial murine adenomas: analyses of mouse chimeras with low
      tumor multiplicity suggest short-range interactions.
AB  - In previous studies demonstrating the polyclonal structure of familial intestinal
      adenomas, high tumor multiplicity made it difficult to eliminate the possibility
      that polyclonality arose by the random collision of distinct initiated clones as
      opposed to some form of clonal interaction. We sought to test further the random
      collision hypothesis. Chimeric mice carrying the multiple intestinal neoplasia
      (Min) mutation of the adenomatous polyposis coli gene (Apc) and homozygous for
      the tumor resistance allele of the Mom1 locus were established. These chimeras
      also display a strong propensity for tumors of polyclonal structure, despite
      their markedly reduced tumor multiplicity. Considering tumor sizes and
      multiplicities, the observed fraction of overtly polyclonal heterotypic adenomas
      was significantly higher than predicted by the random collision hypothesis. This
      finding supports models of polyclonality involving interaction among multiple
      initiated clones. The extent of clonal interaction was assessed by statistical
      analyses that relate the observed frequency of overtly polyclonal heterotypic
      tumors to the geometry of the chimeric patches and the pattern of underlying
      crypts. These statistical calculations indicate that the familial adenomas of the
      Apc(Min/+) mouse may commonly form through interactions between clones as close
      as 1-2 crypt diameters apart.

PMID- 15870187
TI  - Selective anxiolysis produced by ocinaplon, a GABA(A) receptor modulator.
AB  - Benzodiazepines remain widely used for the treatment of anxiety disorders despite
      prominent, often limiting side effects including sedation, muscle relaxation, and
      ataxia. A compound producing a robust anxiolytic action comparable to
      benzodiazepines, but lacking these limiting side effects at therapeutic doses (an
      anxioselective agent), would represent an important advance in the treatment of
      generalized anxiety disorder, and perhaps other anxiety disorders. Here we report
      that the pyrazolo[1,5-a]-pyrimidine, ocinaplon, exhibits an anxioselective
      profile in both preclinical procedures and in patients with generalized anxiety
      disorder, the most common of the anxiety disorders. In rats, ocinaplon produces
      significant muscle relaxation, ataxia, and sedation only at doses >25-fold higher
      than the minimum effective dose (3.1 mg/kg) in the Vogel "conflict" test. This
      anticonflict effect is blocked by flumazenil (Ro 15-1788), indicating that like
      benzodiazepines, ocinaplon produces an anxiolytic action through allosteric
      modulation of GABA(A) receptors. Nonetheless, in eight recombinant GABA(A)
      receptor isoforms expressed in Xenopus oocytes, the potency and efficacy of
      ocinaplon to potentiate GABA responses varied with subunit composition not only
      in an absolute sense, but also relative to the prototypical benzodiazepine,
      diazepam. In a double blind, placebo controlled clinical trial, a 2-week regimen
      of ocinaplon (total daily dose of 180-240 mg) produced statistically significant
      reductions in the Hamilton rating scale for anxiety scores. In this study, the
      incidence of benzodiazepine-like side effects (e.g., sedation, dizziness) in
      ocinaplon-treated patients did not differ from placebo. These findings indicate
      that ocinaplon represents a unique approach both for the treatment and
      understanding of anxiety disorders.

PMID- 15870188
TI  - Balance of actively generated contractile and resistive forces controls
      cytokinesis dynamics.
AB  - Cytokinesis, the fission of a mother cell into two daughter cells, is a simple
      and dramatic cell shape change. Here, we examine the dynamics of cytokinesis by
      using a combination of microscopy, dynamic measurements, and genetic analysis. We
      find that cytokinesis proceeds through a single sequence of shape changes, but
      the kinetics of the transformation from one shape to another differs dramatically
      between strains. We interpret the measurements in a simple and quantitative
      manner by using a previously uncharacterized analytic model. From the analysis,
      wild-type cytokinesis appears to proceed through an active, extremely regulated
      process in which globally distributed proteins generate resistive forces that
      slow the rate of furrow ingression. Finally, we propose that, in addition to
      myosin II, a Laplace pressure, resulting from material properties and the
      geometry of the dividing cell, generates force to help drive furrow ingression
      late in cytokinesis.

PMID- 15870190
TI  - Remarkable diversity of mammalian pheromone receptor repertoires.

PMID- 15870189
TI  - Background gamma rhythmicity and attention in cortical local circuits: a
      computational study.
AB  - We describe a simple computational model, based on generic features of cortical
      local circuits, that links cholinergic neuromodulation, gamma rhythmicity, and
      attentional selection. We propose that cholinergic modulation, by reducing
      adaptation currents in principal cells, induces a transition from asynchronous
      spontaneous activity to a "background" gamma rhythm (resembling the persistent
      gamma rhythms evoked in vitro by cholinergic agonists) in which individual
      principal cells participate infrequently and irregularly. We suggest that such
      rhythms accompany states of preparatory attention or vigilance and report
      simulations demonstrating that their presence can amplify stimulus-specific
      responses and enhance stimulus competition within a local circuit.

PMID- 15870191
TI  - Genomewide production of multipurpose alleles for the functional analysis of the
      mouse genome.
AB  - A type of retroviral gene trap vectors has been developed that can induce
      conditional mutations in most genes expressed in mouse embryonic stem (ES) cells.
      The vectors rely on directional site-specific recombination systems that can
      repair and re-induce gene trap mutations when activated in succession. After the
      gene traps are inserted into the mouse genome, genetic mutations can be produced
      at a particular time and place in somatic cells. In addition to their conditional
      features, the vectors create multipurpose alleles amenable to a wide range of
      post-insertional modifications. Here we have used these directional recombination
      vectors to assemble the largest library of ES cell lines with conditional
      mutations in single genes yet assembled, presently totaling 1,000 unique genes.
      The trapped ES cell lines, which can be ordered from the German Gene Trap
      Consortium, are freely available to the scientific community.

PMID- 15870192
TI  - Identification and analysis of vnd/NK-2 homeodomain binding sites in genomic DNA.
AB  - Vnd/NK-2 homeodomain affinity column chromatography was used to purify Drosophila
      DNA fragments bound by the vnd/NK-2 homeodomain. Sequencing the selected genomic
      DNA fragments led to the identification of 77 Drosophila DNA fragments that were
      grouped into 42 vnd/NK-2 homeodomain-binding loci. Most loci were within upstream
      or intronic regions, especially first introns. Nineteen of the Drosophila DNA
      fragments cloned correspond to one locus, termed Clone A, which is 312 bp in
      length and contains five vnd/NK-2 homeodomain core consensus binding sites, 5'
      AAGTG, and is part of the first intron of the Beadex gene. We further analyzed
      the interactions between Clone A and vnd/NK-2 homeodomain protein by mobility
      shift assay, DNase I footprinting, methylation interference, and ethylation
      interference. The DNase I footprinting analysis of Clone A with vnd/NK-2
      homeodomain protein revealed three strong binding sites and one weak binding site
      between 15 and 130 bp of Clone A. We also analyzed binding of the vnd/NK-2
      homeodomain to the 5'-flanking sequence of vnd/NK-2 genomic DNA. The DNase I
      footprinting result showed that there are two strong binding sites and five weak
      binding sites in the fragment between -385 and -675 bp from the transcription
      start site of the vnd/NK-2 gene.

PMID- 15870193
TI  - Phylogeography of Barbary macaques (Macaca sylvanus) and the origin of the
      Gibraltar colony.
AB  - The Barbary macaque (Macaca sylvanus) is the earliest offshoot of the genus
      Macaca and the only extant African representative, all other species being
      Asiatic. Once distributed throughout North Africa, M. sylvanus is now restricted
      to isolated forest fragments in Algeria and Morocco. The species is threatened;
      the maximum total wild population size is estimated at 10,000 individuals.
      Relationships among surviving wild subpopulations in Algeria (96 samples) and
      Morocco (116 samples) were examined by using 468-bp sequences from hypervariable
      region I of the mitochondrial DNA control region. Twenty-four different
      haplotypes were identified, differing by 1-26 mutational steps (0.2-5.6%) and 1
      insertion. With one exception (attributable to secondary introduction in coastal
      Morocco), Algerian and Moroccan haplotypes are clearly distinct. However, whereas
      Moroccan subpopulations show little divergence in hypervariable region I
      sequences and little correspondence with geographical distribution, there is a
      deep division between two main subpopulations in Algeria and one marked secondary
      division, with haplotypes generally matching geographical distribution. Accepting
      an origin of the genus Macaca of 5.5 million years ago, the Moroccan population
      and the two main Algerian subpopulations diverged approximately 1.6 million years
      ago. Distinction between Moroccan and Algerian haplotypes permitted analysis of
      the origin of the Gibraltar colony of Barbary macaques (68 samples; 30% of the
      population). It is generally held that the present Gibraltar population descended
      from a dozen individuals imported during World War II. However, the Gibraltar
      sample was found to include Algerian and Moroccan haplotypes separated by at
      least 16 mutational steps, revealing a dual origin of the founding females.

PMID- 15870194
TI  - Human biliverdin reductase: a member of the insulin receptor substrate family
      with serine/threonine/tyrosine kinase activity.
AB  - We describe here the tyrosine kinase activity of human biliverdin reductase (BVR)
      and its potential role in the insulin-signaling pathway. BVR is both a substrate
      for insulin receptor (IR) tyrosine kinase (IRK) activity and a kinase for serine
      phosphorylation of IR substrate 1 (IRS-1). Our previous studies have revealed
      serine/threonine kinase activity of BVR. Y198, in the YMKM motif found in the C
      terminal domain of BVR, is shown to be a substrate for insulin-activated IRK.
      This motif in IRS proteins provides a docking site for proteins that contain a
      Src homology 2 domain. Additionally, Y228 in the YLSF sequence and Y291 are IRK
      substrates; the former sequence provides optimum recognition motif in the
      tyrosine phosphatase, SHP-1, and for SHC (Src homology 2 domain containing
      transfroming protein 1). BVR autophosphorylates N-terminal tyrosines Y72 and Y83.
      Serine residues in IRS-1 are targets for BVR phosphorylation, and point mutation
      of serine residues in the kinase domain of the reductase inhibits
      phosphotransferase activity. Because tyrosine phosphorylation of IRS-1 activates
      the insulin signaling pathway and serine phosphorylation of IRS-1 blocks insulin
      action, our findings that insulin increases BVR tyrosine phosphorylation and that
      there is an increase in glucose uptake in response to insulin when expression of
      BVR is "knocked down" by small interfering RNA suggest a potential role for BVR
      in the insulin signaling pathway.

PMID- 15870195
TI  - Point mutation in AML1 disrupts subnuclear targeting, prevents myeloid
      differentiation, and effects a transformation-like phenotype.
AB  - The multifunctional C terminus of the hematopoietic AML1 transcription factor
      interacts with coregulatory proteins, supports the convergence and integration of
      physiological signals, and contains the nuclear matrix targeting signal, the
      protein motif that is necessary and sufficient to target AML1 to subnuclear
      sites. The (8;21) chromosomal translocation, which replaces the C terminus of
      AML1 with the ETO protein, modifies subnuclear targeting of AML1 in acute myeloid
      leukemia (AML) and results in defective myelopoiesis. We therefore addressed the
      relevance of AML1 subnuclear targeting and associated functions that reside in
      the C terminus to myeloid differentiation. A single amino acid substitution that
      abrogates intranuclear localization was introduced in the AML1 subnuclear
      targeting signal. Expression of the mutant AML1 protein blocks differentiation of
      myeloid progenitors to granulocytes in the presence of endogenous AML1 protein,
      as also occurs in the (8;21) chromosomal translocation, where only one allele of
      the AML1 gene is affected. The cells expressing the mutant AML1 protein continue
      to proliferate, maintain an immature blast-like morphology, and exhibit
      transformed properties that are hallmarks of leukemogenesis. These findings
      functionally link AML1 subnuclear targeting with competency for myeloid
      differentiation and expression of the transformed/leukemia phenotype.

PMID- 15870196
TI  - Controlled fabrication of hierarchically branched nanopores, nanotubes, and
      nanowires.
AB  - Here, we report a generic synthetic approach to rationally design multiply
      connected and hierarchically branched nanopores inside anodic aluminum oxide
      templates. By using these nanochannels, we controllably fabricate a large variety
      of branched nanostructures, far more complex than what exists today. These
      nanostructures include carbon nanotubes and metallic nanowires having several
      hierarchical levels of multiple branching. The number and frequency of branching,
      dimensions, and the overall architecture are controlled precisely through pore
      design and templated assembly. The technique provides a powerful approach to
      produce nanostructures of greater morphological complexity, which could have far
      reaching implications in the design of future nanoscale systems.

PMID- 15870197
TI  - Bone morphogenetic protein 9 induces the transcriptome of basal forebrain
      cholinergic neurons.
AB  - Basal forebrain cholinergic neurons (BFCN) participate in processes of learning,
      memory, and attention. Little is known about the genes expressed by BFCN and the
      extracellular signals that control their expression. Previous studies showed that
      bone morphogenetic protein (BMP) 9 induces and maintains the cholinergic
      phenotype of embryonic BFCN. We measured gene expression patterns in septal
      cultures of embryonic day 14 mice and rats grown in the presence or absence of
      BMP9 by using species-specific microarrays and validated the RNA expression data
      of selected genes by immunoblot and immunocytochemistry analysis of their protein
      products. BMP9 enhanced the expression of multiple genes in a time-dependent and,
      in most cases, reversible manner. The set of BMP9-responsive genes was concordant
      between mouse and rat and included genes encoding cell-cycle/growth control
      proteins, transcription factors, signal transduction molecules, extracellular
      matrix, and adhesion molecules, enzymes, transporters, and chaperonins. BMP9
      induced the p75 neurotrophin receptor (NGFR), a marker of BFCN, and Cntf and
      Serpinf1, two trophic factors for cholinergic neurons, suggesting that BMP9
      creates a trophic environment for BFCN. To determine whether the genes induced by
      BMP9 in culture were constituents of the BFCN transcriptome, we purified BFCN
      from embryonic day 18 mouse septum by using fluorescence-activated cell sorting
      of NGFR(+) cells and profiled mRNA expression of these and NGFR(-) cells.
      Approximately 30% of genes induced by BMP9 in vitro were overexpressed in
      purified BFCN, indicating that they belong to the BFCN transcriptome in situ and
      suggesting that BMP signaling contributes to maturation of BFCN in vivo.

PMID- 15870198
TI  - STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1
      tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes.
AB  - Expression of SHP-1 phosphatase, a key negative regulator of cell signaling, is
      lost in T cell lymphomas and other malignancies due to DNA methylation of the SHP
      1 promoter by a currently undefined mechanism. We demonstrate that malignant T
      cells express DNA methyltransferase (DNMT) 1 and that constantly activated signal
      transducer and activator of transcription (STAT) 3 is capable of binding in vitro
      to DNA oligonucleotides corresponding to four STAT3 SIE/GAS binding sites
      identified in the SHP-1 promoter. STAT3, DNMT1, and histone deacetylase 1 form
      complexes and bind to the SHP-1 promoter in vivo. Treatment with pharmacologic
      grade DNMT1 anti-sense oligonucleotides and STAT3 small-interfering RNA induces
      in the malignant T cells DNA demethylation and expression of SHP-1 gene. These
      data indicate that STAT3 may, in part, transform cells by inducing epigenetic
      silencing of SHP-1 in cooperation with DNMT1 and, apparently, histone deacetylase
      1. Reversal of such gene silencing represents an attractive aim for novel
      anticancer therapies.

PMID- 15870199
TI  - A common haplotype in the complement regulatory gene factor H (HF1/CFH)
      predisposes individuals to age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the most frequent cause of irreversible
      blindness in the elderly in developed countries. Our previous studies implicated
      activation of complement in the formation of drusen, the hallmark lesion of AMD.
      Here, we show that factor H (HF1), the major inhibitor of the alternative
      complement pathway, accumulates within drusen and is synthesized by the retinal
      pigmented epithelium. Because previous linkage analyses identified chromosome
      1q25-32, which harbors the factor H gene (HF1/CFH), as an AMD susceptibility
      locus, we analyzed HF1 for genetic variation in two independent cohorts comprised
      of approximately 900 AMD cases and 400 matched controls. We found association of
      eight common HF1 SNPs with AMD; two common missense variants exhibit highly
      significant associations (I62V, chi2 = 26.1 and P = 3.2 x 10(-7) and Y402H, chi2
      = 54.4 and P = 1.6 x 10(-13)). Haplotype analysis reveals that multiple HF1
      variants confer elevated or reduced risk of AMD. One common at-risk haplotype is
      present at a frequency of 50% in AMD cases and 29% in controls [odds ratio (OR) =
      2.46, 95% confidence interval (1.95-3.11)]. Homozygotes for this haplotype
      account for 24% of cases and 8% of controls [OR = 3.51, 95% confidence interval
      (2.13-5.78)]. Several protective haplotypes are also identified (OR = 0.44-0.55),
      further implicating HF1 function in the pathogenetic mechanisms underlying AMD.
      We propose that genetic variation in a regulator of the alternative complement
      pathway, when combined with a triggering event, such as infection, underlie a
      major proportion of AMD in the human population.

PMID- 15870200
TI  - Isolation and characterization of a retinal pigment epithelial cell fluorophore:
      an all-trans-retinal dimer conjugate.
AB  - Several lines of investigation suggest that the nondegradable fluorophores that
      accumulate as lipofuscin in retinal pigment epithelium (RPE) cells contribute to
      the etiology of macular degeneration. Despite evidence that much of this
      fluorescent material may originate as inadvertent products of the retinoid cycle,
      the enzymatic pathway by which the 11-cis-retinal chromophore of rhodopsin is
      generated, the only fluorophores of the RPE to be characterized as yet have been
      A2E and its isomers. Here, we report the isolation and structural
      characterization of an additional RPE lipofuscin fluorophore that originates as a
      condensation product of two molecules of all-trans-retinal (ATR) dimer and forms
      a protonated Schiff base conjugate with phosphatidylethanolamine (PE), the latter
      conjugate (ATR dimer-PE) having UV-visible absorbance maxima at 285 and 506 nm.
      ATR dimer was found to form natively in bleached rod outer segments in vitro and
      when rod outer segments were incubated with ATR. HPLC analysis of eye-cups that
      included RPE and isolated neural retina from Abcr-/- mice and RPE isolated from
      human donor eyes revealed the presence of a pigment with the same UV-visible
      absorbance and retention time as synthetic ATR dimer-PE conjugate. Evidence that
      ATR dimer undergoes a photooxidation process involving the addition of oxygens at
      double bonds as well as an aromatic demethylation also may indicate a role for
      this molecule, or its derivatives, in the photoreactivity of RPE lipofuscin.

PMID- 15870201
TI  - Molecular dynamics studies of heterogeneous dynamics and dynamic crossover in
      supercooled atomic liquids.
AB  - Supercooled liquids near the glass transition exhibit the phenomenon of
      heterogeneous relaxation; at any specific time, a nominally homogeneous
      equilibrium fluid undergoes dynamic fluctuations in its structure on a molecular
      distance scale with rates that are very different in different regions of the
      sample. Several theoretical and simulation studies have suggested a change in the
      nature of the dynamics of fluids as they are supercooled, leading to the concept
      of a dynamic crossover that is often associated with mode coupling theory. Here,
      we will review the use of molecular dynamics computer simulation methods to
      investigate heterogeneous dynamics and dynamic crossovers in models of atomic
      liquids.

PMID- 15870202
TI  - Exogenous nitric oxide reduces glucose transporters translocation and lactate
      production in ischemic myocardium in vivo.
AB  - Nitric oxide (NO) inhibits myocardial glucose transport and metabolism, although
      the underlying mechanism(s) and functional consequences of this effect are not
      clearly understood. We tested the hypothesis that NO inhibits the activation of
      AMP-activated protein kinase (AMPK) and translocation of cardiac glucose
      transporters (GLUTs; GLUT-4) and reduces lactate production. Ischemia was induced
      in open-chest dogs by a 66% flow reduction in the left anterior descending
      coronary artery (LAD). During ischemia, dogs were untreated (control) or treated
      by direct LAD infusion of (i) nitroglycerin (NTG) (0.5 microg.kg(-1).min(-1));
      (ii) 8-Br-cGMP (50 microg.kg(-1).min(-1)); or (iii) NO synthase inhibitor L-nitro
      argininemethylester (40 microg.kg(-1).min(-1); n = 9 per group). Cardiac
      substrate oxidation was measured with isotopic tracers. There were no differences
      in myocardial blood flow or oxygen delivery among groups; however, at 45 min of
      ischemia, the activation of AMPK was significantly less in NTG (77 +/- 12% vs.
      nonischemic myocardium) and 8-Br-cGMP (104 +/- 13%), compared with control (167
      +/- 17%). Similarly, GLUT-4 translocation was significantly reduced in NTG (74 +/
      7%) and 8-Br-cGMP (120 +/- 11%), compared with control (165 +/- 17%). Glucose
      uptake and lactate output were 30% and 60% lower in NTG compared with control.
      Inhibition of NO synthesis stimulated glucose oxidation (67% increase compared
      with control) but did not affect AMPK phosphorylation, GLUT-4 translocation and
      glucose uptake. Contractile function in the ischemic region was significantly
      improved by NTG and L-nitro-argininemethylester. In conclusion, in ischemic
      myocardium an NO donor inhibits glucose uptake and lactate production via a
      reduction in AMPK stimulation of GLUT-4 translocation, revealing a mechanism of
      metabolic modulation and myocardial protection activated by NO donors.

PMID- 15870203
TI  - Specific correlation between the wobble modification deficiency in mutant tRNAs
      and the clinical features of a human mitochondrial disease.
AB  - Mutations in mtDNA are responsible for a variety of mitochondrial diseases, where
      the mitochondrial tRNA(Leu(UUR)) gene has especially hot spots for pathogenic
      mutations. Clinical features often depend on the tRNA species and/or positions of
      the mutations; however, molecular pathogenesis elucidating the relation between
      the location of the mutations and their leading phenotype are not fully
      understood. We report here that mitochondrial tRNAs(Leu(UUR)) harboring one of
      five mutations found in tissues from patients with symptoms of mitochondrial
      myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)
      (A3243G, G3244A, T3258C, T3271C, and T3291C) lacked the normal taurine-containing
      modification (5-taurinomethyluridine) at the anticodon wobble position. In
      contrast, mitochondrial tRNAs(Leu(UUR)) with different mutations found in
      patients that have mitochondrial diseases but do not show the MELAS symptoms
      (G3242A, T3250C, C3254T, and A3280G) had the normal 5-taurinomethyluridine
      modifications. These observations were made by using a modified primer extension
      technique that can detect the modification deficiency in the extremely limited
      quantities of mutant tRNAs obtainable from patient tissues. These results
      strongly suggest deficient wobble modification could be a key molecular factor
      responsible for the phenotypic features of MELAS, which can explain why the
      different MELAS-associated mutations result in indistinguishable clinical
      features.

PMID- 15870204
TI  - Ab initio molecular dynamics: concepts, recent developments, and future trends.
AB  - The methodology of ab initio molecular dynamics, wherein finite-temperature
      dynamical trajectories are generated by using forces computed "on the fly" from
      electronic structure calculations, has had a profound influence in modern
      theoretical research. Ab initio molecular dynamics allows chemical processes in
      condensed phases to be studied in an accurate and unbiased manner, leading to new
      paradigms in the elucidation of microscopic mechanisms, rationalization of
      experimental data, and testable predictions of new phenomena. The purpose of this
      work is to give a brief introduction to the technique and to review several
      important recent developments in the field. Several illustrative examples showing
      the power of the technique have been chosen. Perspectives on future directions in
      the field also will be given.

PMID- 15870205
TI  - Recombinant granulocyte colony-stimulating factor-transferrin fusion protein as
      an oral myelopoietic agent.
AB  - An expression construct harboring granulocyte colony-stimulating factor (G-CSF)
      transferrin (Tf) fusion protein (G-CSF-Tf) was engineered by fusing human cDNAs
      encoding G-CSF and Tf to explore the feasibility of using Tf as a carrier moiety
      for oral delivery of therapeutic proteins. The recombinant protein, G-CSF-Tf, was
      harvested from protein-free, conditioned medium of transfected HEK293 cells. The
      in vitro studies demonstrated that the purified G-CSF-Tf fusion protein possesses
      the activity of both Tf receptor (TfR) binding in Caco-2 cells and G-CSF
      dependent stimulation of NFS-60 cell proliferation. Subcutaneous administration
      of G-CSF-Tf fusion protein to BDF1 mice demonstrated a pharmacological effect
      comparable to the commercial G-CSF on the increase of absolute neutrophil counts
      (ANC). However, the fusion protein elicited a significant increase in ANC upon
      oral administration to BDF1 mice, whereas G-CSF had no effect. This study also
      showed that orally administered G-CSF-Tf elicits a sustained myelopoietic effect
      up to 3 days, whereas the s.c. administered G-CSF or G-CSF-Tf lasts only 1 day.
      Furthermore, coadministration of free Tf abolished the increase of ANC by orally
      delivered G-CSF-Tf, suggesting that the recombinant protein is absorbed via a TfR
      mediated process in the gastrointestinal tract. Taken together, we conclude that
      the Tf-based recombinant fusion protein technology represents a promising
      approach for future development of orally effective peptide and protein drugs.

PMID- 15870206
TI  - How sequence defines structure: a crystallographic map of DNA structure and
      conformation.
AB  - The fundamental question of how sequence defines conformation is explicitly
      answered if the structures of all possible sequences of a macromolecule are
      determined. We present here a crystallographic screen of all permutations of the
      inverted repeat DNA sequence d(CCnnnN6N7N8GG), where N6, N7, and N8 are any of
      the four naturally occurring nucleotides. At this point, 63 of the 64 possible
      permutations have been crystallized from a defined set of solutions. When
      combined with previous work, we have assembled a data set of 37 single-crystal
      structures from 29 of the sequences in this motif, representing three structural
      classes of DNA (B-DNA, A-DNA, and four-stranded Holliday junctions). This data
      set includes a unique set of amphimorphic sequence, those that crystallize in two
      different conformations and serve to bridge the three structural phases. We have
      thus constructed a map of DNA structures that can be walked through in single
      nucleotide steps. Finally, the resulting data set allows us to dissect in detail
      the stabilization of and conformational variations within structural classes and
      identify significant conformational deviations within a particular structural
      class that result from sequence rather than crystal or crystallization effects.

PMID- 15870207
TI  - Visualizing reaction pathways in photoactive yellow protein from nanoseconds to
      seconds.
AB  - Determining 3D intermediate structures during the biological action of proteins
      in real time under ambient conditions is essential for understanding how proteins
      function. Here we use time-resolved Laue crystallography to extract short-lived
      intermediate structures and thereby unveil signal transduction in the blue light
      photoreceptor photoactive yellow protein (PYP) from Halorhodospira halophila. By
      analyzing a comprehensive set of Laue data during the PYP photocycle (forty-seven
      time points from one nanosecond to one second), we track all atoms in PYP during
      its photocycle and directly observe how absorption of a blue light photon by its
      p-coumaric acid chromophore triggers a reversible photocycle. We identify a
      complex chemical mechanism characterized by five distinct structural
      intermediates. Structural changes at the chromophore in the early, red-shifted
      intermediates are transduced to the exterior of the protein in the late, blue
      shifted intermediates through an initial "volume-conserving" isomerization of the
      chromophore and the progressive disruption of hydrogen bonds between the
      chromophore and its surrounding binding pocket. These results yield a
      comprehensive view of the PYP photocycle when seen in the light of previous
      biophysical studies on the system.

PMID- 15870208
TI  - Molecular dynamics and protein function.
AB  - A fundamental appreciation for how biological macromolecules work requires
      knowledge of structure and dynamics. Molecular dynamics simulations provide
      powerful tools for the exploration of the conformational energy landscape
      accessible to these molecules, and the rapid increase in computational power
      coupled with improvements in methodology makes this an exciting time for the
      application of simulation to structural biology. In this Perspective we survey
      two areas, protein folding and enzymatic catalysis, in which simulations have
      contributed to a general understanding of mechanism. We also describe results for
      the F(1) ATPase molecular motor and the Src family of signaling proteins as
      examples of applications of simulations to specific biological systems.

PMID- 15870209
TI  - Quantum dynamics of complex molecular systems.
AB  - This Perspective presents a broad overview of the present status of theoretical
      capabilities for describing quantum dynamics in molecular systems with many
      degrees of freedom, e.g., chemical reactions in solution, clusters, solids, or
      biomolecular environments.

PMID- 15870210
TI  - Materials by numbers: computations as tools of discovery.
AB  - Current issues pertaining to theoretical simulations of materials, with a focus
      on systems of nanometer-scale dimensions, are discussed. The use of atomistic
      simulations as high-resolution numerical experiments, enabling and guiding
      formulation and testing of analytic theoretical descriptions, is demonstrated
      through studies of the generation and breakup of nanojets, which have led to the
      derivation of a stochastic hydrodynamic description. Subsequently, I illustrate
      the use of computations and simulations as tools of discovery, with examples that
      include the self-organized formation of nanowires, the surprising nanocatalytic
      activity of small aggregates of gold that, in the bulk form, is notorious for
      being chemically inert, and the emergence of rotating electron molecules in two
      dimensional quantum dots. I conclude with a brief discussion of some key
      challenges in nanomaterials simulations.

PMID- 15870211
TI  - Potential energy functions for atomic-level simulations of water and organic and
      biomolecular systems.
AB  - An overview is provided on the development and status of potential energy
      functions that are used in atomic-level statistical mechanics and molecular
      dynamics simulations of water and of organic and biomolecular systems. Some
      topics that are considered are the form of force fields, their parameterization
      and performance, simulations of organic liquids, computation of free energies of
      hydration, universal extension for organic molecules, and choice of atomic
      charges. The discussion of water models covers some history, performance issues,
      and special topics such as nuclear quantum effects.

PMID- 15870212
TI  - Ab initio quantum chemistry: methodology and applications.
AB  - This Perspective provides an overview of state-of-the-art ab initio quantum
      chemical methodology and applications. The methods that are discussed include
      coupled cluster theory, localized second-order Moller-Plesset perturbation
      theory, multireference perturbation approaches, and density functional theory.
      The accuracy of each approach for key chemical properties is summarized, and the
      computational performance is analyzed, emphasizing significant advances in
      algorithms and implementation over the past decade. Incorporation of a condensed
      phase environment by means of mixed quantum mechanical/molecular mechanics or
      self-consistent reaction field techniques, is presented. A wide range of
      illustrative applications, focusing on materials science and biology, are
      discussed briefly.

PMID- 15870213
TI  - Release of oxidized plastocyanin from photosystem I limits electron transfer
      between photosystem I and cytochrome b6f complex in vivo.
AB  - We used fast absorbance spectroscopy to investigate in vivo binding dynamics and
      electron transfer between plastocyanin (pc) and photosystem I (PSI), and
      cytochrome (cyt) f oxidation kinetics in Chlamydomonas reinhardtii mutants in
      which either the binding or the release of pc from PSI was diminished. Under
      single flash-excitation conditions, electron flow between PSI and the cyt complex
      was not affected by a 5-fold lowering of the binding affinity of pc to PSI, as
      induced by a mutation replacing the tryptophan-651 of the PsaA subunit by a
      serine residue (PsaA-W651S). On the other hand, electron flow from PSI to the cyt
      b(6)f complex was very sensitive to a 2- to 3-fold decrease in the rate of pc
      release from PSI, obtained by replacing the glutamic acid residue 613 of the PsaB
      subunit with glutamine (PsaB-E613N). Thus, our data indicate that under these
      experimental conditions the release of oxidized pc limits electron transfer
      between cyt b(6)f complex and PSI in vivo.

PMID- 15870214
TI  - Functional expression cloning reveals a central role for the receptor for
      activated protein kinase C 1 (RACK1) in T cell apoptosis.
AB  - Mammalian cDNA expression cloning was used to identify novel genes that regulate
      apoptosis. Using a functional screen, we identified a partial cDNA for the
      receptor for activated protein kinase C 1 (RACK1) through selection for
      resistance to phytohemagglutinin and gamma-irradiation. Expression of this
      partial cDNA in T cell lines using a mammalian expression vector produced an
      increase in RACK1 expression and resulted in resistance to dexamethasone- and
      ultraviolet-induced apoptosis. Down-regulation of RACK1 using RNA interference
      abolished the resistance of the transfected cells to apoptosis. Overexpression of
      full-length RACK1 also resulted in the suppression of apoptosis mediated by
      several apoptotic stimuli, and this effect was quantitatively consistent with the
      effects of the original cDNA isolated on endogenous RACK1 levels. Together, these
      findings suggest that RACK1 plays an important role in the intracellular
      signaling pathways that lead to apoptosis in T cells.

PMID- 15870215
TI  - Long-term follow-up of atherosclerotic renovascular disease. Beneficial effect of
      ACE inhibition.
AB  - BACKGROUND: Patients with atherosclerotic renovascular disease (ARVD) are almost
      invariably treated by revascularization. However, the long-term outcomes of this
      approach on survival and progression to renal failure have not been investigated
      and have not been compared with that of a purely medical treatment. The aim of
      this observational study was to investigate factors affecting long-term (over 5
      years) outcome, survival and renal function of patients with ARVD treated
      invasively or medically. METHODS: ARVD was demonstrated angiographically in 195
      patients who were consecutively enrolled into a follow-up study. Patient age was
      65.6+/-11.2 years, serum creatinine was 1.74+/-1.22 mg/dl and renal artery lumen
      narrowing was 73.5+/-17.5%. A revascularization was performed in 136 patients,
      whereas 54 subjects having comparable characteristics were maintained on a
      medical treatment throughout the study; five patients were lost during follow-up.
      RESULTS: The main follow-up was 54.4+/-40.4 months. The assessment of
      cardiovascular survival and renal survival at the end of follow-up revealed 46
      cardiovascular deaths, 20 patients with end-stage renal disease (ESRD) and 41
      patients with an increase in serum creatinine of over one-third. The multivariate
      analysis showed that renal revascularization did not affect mortality or renal
      survival compared with medical treatment. Revascularization produced slightly
      lower increases in serum creatinine and a better control of blood pressure. A
      longer survival was associated with the use of angiotensin-converting enzyme
      inhibitors (ACEIs) (P = 0.002) in both revascularized and medically treated
      patients. The only significant predictor of ESRD was an abnormal baseline serum
      creatinine. CONCLUSIONS: On long-term follow-up, ARVD was associated with a poor
      prognosis due to a high cardiovascular mortality and a high rate of ESRD. In our
      non-randomized study, revascularization was not a major advantage over medical
      treatment in terms of mortality or renal survival. The use of ACEIs was
      associated with improved survival.

PMID- 15870216
TI  - Timing of first cannulation of arteriovenous fistula: time matters, but there is
      also something else.

PMID- 15870217
TI  - Effect of alcohol consumption on estimated glomerular filtration rate and
      creatinine clearance rate.
AB  - BACKGROUND: Moderate alcohol consumption is widely recognized as beneficial in
      the prevention of cardiovascular disease, yet the renal effects of alcohol intake
      are still controversial. The present study is designed to investigate the
      influence of alcohol consumption on calculated creatinine clearance rate (CCr)
      and glomerular filtration rate (GFR) in a Southern Taiwan Pai-Wan aboriginal
      community with a high prevalence of alcohol consumption. METHODS: This is a cross
      sectional community-based study. The 1466 aboriginal subjects, 40-95 years of
      age, are a stratified random subpopulation identified during an integrative
      health care programme. They were sampled for drinking patterns. The main outcome
      measurements were serum creatinine, estimated CCr and GFR. RESULTS: Subjects with
      alcohol consumption had significantly higher levels of serum triglycerides, high
      density lipoprotein cholesterol, uric acid, estimated CCr and GFR values than non
      drinkers. Their blood pressure was also significantly higher. They had lower
      total cholesterol and low-density lipoprotein cholesterol concentrations.
      Increasing alcohol consumption was independently and significantly associated
      with a higher level of estimated CCr and GFR when analysed as both a categorical
      and continuous variable. CONCLUSIONS: The present study shows that chronic
      alcohol consumption has a negative effect on blood pressure and lipid profile and
      stimulates the estimated GFR.

PMID- 15870219
TI  - Did syphilis truly strike the kidneys this time?

PMID- 15870218
TI  - Rapid resolution of calciphylaxis with intravenous sodium thiosulfate and
      continuous venovenous haemofiltration using low calcium replacement fluid: case
      report.

PMID- 15870220
TI  - Glomerular hyperfiltration and hypertrophy in the rat hypoplastic kidney as a
      model of oligomeganephronic disease.
AB  - BACKGROUND: Rat male hypogonadisim (hgn/hgn) is accompanied by bilateral
      hypoplastic kidney (HPK). The HPK contains a reduced number of nephrons that
      progress to chronic renal failure. In this study, we describe the renal
      pathophysiology in adult HPK rats as a potential model of oligomeganephronic
      disease. METHODS: Urine and blood samples were collected from adult male HPK rats
      and phenotypically normal littermates at 70 days of age for measurements of urea
      nitrogen and creatinine clearances (Cun and Ccr). Glomerular number (GN) and
      glomerular projective area were determined using the maceration method. Blood
      pressure was measured. Urinary protein and renal histology were examined. Urinary
      albumin concentration was determined at early postnatal ages. RESULTS: Renal
      weight was significantly smaller in adult HPK males than in normal males.
      Polyuria and polydipsia were observed in HPK rats. Ccr and Cun were low in HPK
      rats compared with those in normal rats. The HPK contained only 20% of the
      nephrons present in normal kidneys. The Cun and Ccr divided by GN (average values
      of single nephron Cun and Ccr) of HPK rats were about two and four times greater
      than normal levels, respectively. This hyperfiltration was not accompanied by
      systemic hypertension, but was associated with marked glomerular hypertrophy and
      glomerulosclerosis, which were observed mainly in the inner cortex. A
      considerable heterogeneity of glomerular size was found in HPK and most glomeruli
      of surface nephrons retained normal size and histology. A remarkable leakage of
      albumin into urine was found at 35 and 70 days of age. CONCLUSIONS: The HPK rat
      is a useful model for studying the pathophysiology of oligomeganephronic disease
      as well as glomerular hyperfiltration and hypertrophy induced by severe
      congenital reduction of nephrons.

PMID- 15870221
TI  - Nicotinamide prevents the development of hyperphosphataemia by suppressing
      intestinal sodium-dependent phosphate transporter in rats with adenine-induced
      renal failure.
AB  - BACKGROUND: Nicotinamide has been shown to inhibit intestinal sodium-dependent
      phosphate transport activity in normal rats. It was reported recently that type
      IIb sodium-dependent phosphate co-transporter (NaPi-2b) is a carrier of
      intestinal phosphate absorption, and that its expression level is regulated by
      serum 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and Pi levels in normal rats.
      However, in chronic renal failure (CRF), serum 1,25(OH)(2)D and Pi levels are
      often abnormal. In a rat model of CRF, we investigated whether short-term
      nicotinamide administration was effective in reducing intestinal phosphate
      absorption and, if so, whether the effect was mediated by intestinal NaPi-2b.
      METHODS: Adenine-induced CRF rats were given a single daily intrapenitoneal
      administration of nicotinamide or vehicle solution for 6 days, and time course
      changes in serum Pi, Ca, blood urea nitrogen (BUN) and creatinine levels were
      monitored. Intestinal phosphate absorption was examined by oral administration of
      radiolabelled phosphate on the final day. In addition, NaPi-2b protein content in
      jejunum brush border membranes was determined. RESULTS: Nicotinamide prevented
      the progressive increase in serum Pi associated with renal failure and
      significantly inhibited intestinal Pi absorption as assessed by the influx of
      orally administered radiolabelled phosphate into the circulation. This effect was
      accompanied by a decrease in NaPi-2b expression in jejunum brush border
      membranes. In addition, nicotinamide treatment was also associated with less
      marked elevations in BUN and serum creatinine and a higher creatinine clearance.
      CONCLUSIONS: Nicotinamide inhibited intestinal Pi absorption in a rat model of
      CRF, at least in part by inhibiting the expression of NaPi-2b, and appeared to
      protect against the deterioration of renal function.

PMID- 15870222
TI  - Hypothalamic release of nitric oxide and interaction with amino acid
      neurotransmitters in chronically uraemic rats.
AB  - BACKGROUND: The activity of the hypothalamic gonadotrophin-releasing hormone
      (GnRH) pulse generator is diminished in uraemia. Since GnRH release is influenced
      by nitric oxide (NO) neurotransmission, we examined the integrity of hypothalamic
      NO neurotransmission in the chronically uraemic rat model. METHODS: Adult male
      castrated rats were rendered uraemic by two-stage 5/6 nephrectomy. Basal, N
      methyl-D-aspartate (NMDA)-stimulated and DL-2-amino-5-phosphonovaleric acid (AP
      5)-inhibited NO outflow was measured in uraemic and sham-nephrectomized control
      animals via a microdialysis probe in the medial preoptic area (MPOA). The
      influence of the noradrenergic system was evaluated by blocking noradrenergic
      neurons with N-(2-chloroethyl)-N-ethyl 2-bromobenzylamine (DSP-4). The activity
      of different NO synthase (NOS) isoforms was investigated by administration of the
      isoform-specific NOS inhibitors S-methyl-L-thiocitrulline (SMLT) and L-N6-(1
      iminoethyl)-lysine (L-NIL). Moreover, hypothalamic mRNA expression of the
      individual NOS isoforms was quantitated by real-time reverse transcriptase
      polymerase chain reaction. Effects of NO on amino acid outflow were assessed by
      addition of the NO donor S-nitroso-N-acetyl-penicillamine (SNAP). RESULTS: The
      expression of different NOS species and basal NO outflow did not differ between
      uraemic and control animals. Administration of the NO donor SNAP increased local
      NO production and amino acid outflow similarly in both groups. SMLT but not L
      NIL, an inhibitor of the inducible NOS isoform, reduced NO outflow in both
      groups. AP-5 equally decreased, and noradrenergic blockade increased NMDA
      stimulated NO outflow in both groups. CONCLUSIONS: NO is produced locally and may
      interfere with amino acid neurotransmission in the rat MPOA. Uraemia did not
      interfere with NO neurotransmission in our study.

PMID- 15870223
TI  - Length of interdialytic interval influences serum calcium and phosphorus
      concentrations.
AB  - BACKGROUND: Higher levels of serum phosphorus and calcium are associated with
      increased haemodialysis (HD) patient mortality. Both of these factors act
      synergistically to promote vascular smooth muscle differentiation to an
      osteoblast-like phenotype and subsequent vascular calcification. The aim of this
      study was to investigate the influence of interdialytic interval on serum levels,
      as well as the influence of oral calcium-based phosphate binder load on the
      magnitude of the observed differences. METHODS: We studied 100 patients
      undergoing HD three times per week, over a 2 week period. Haemoglobin, albumin,
      calcium and phosphate were measured pre-dialysis before each HD session. Oral
      phosphate binder usage was recorded. All patients were treated with dialysate
      containing 1.25 mEq/l calcium. RESULTS: Both mean serum phosphate and calcium
      were higher after the long interdialytic interval (1.59+/-0.05 vs 1.45+/-0.04
      mmol/l, P = 0.0005, and 2.46+/-0.03 vs 2.4+/-0.02 mmol/l, P = 0.001, for serum
      phosphate and uncorrected calcium, respectively). There were no significant
      differences in haemoglobin or serum albumin, indicating that variable dilution
      from an increased hydration status in the long interdialytic interval was
      unlikely to contribute to these observed differences. A total of 74 patients were
      treated with calcium-containing binders and 26 patients with sevelamer. Patients
      on sevelamer did not exhibit the observed cyclical increase in serum calcium seen
      in patients on calcium-containing binders (mean difference in serum calcium
      0.09+/-0.01 mmol/l in the calcium-treated group vs 0.01+/-0.01 mmol/l in the
      sevelamer-treated patients, P = 0.0004). The increase in serum calcium after the
      long interval as compared with the short interval was proportional to the daily
      amount of the oral calcium-containing binder load ingested (r = 0.63, P<0.0001).
      CONCLUSION: Cyclical differences in interdialytic interval and overall exposure
      to both dietary phosphate and oral calcium load influence serum levels. This may
      have consequences for registry reporting, therapy modulation and potentially the
      pathogenesis of accelerated vascular calcification seen in HD patients.

PMID- 15870224
TI  - Salt-sensitive blood pressure--an intermediate phenotype predisposing to diabetic
      nephropathy?
AB  - BACKGROUND: Family studies point to important genetic determinants of diabetic
      nephropathy (DN). Blood pressure (BP) is higher in offspring of patients with
      type 2 diabetes and DN, but the pathomechanisms involved have not been
      elucidated. METHODS: We examined the salt sensitivity of BP after 5 days
      equilibration on a low (20 mmol/day) vs high salt diet (220 mmol/day) in three
      matched groups of 15 subjects each: (i) control individuals; (ii) offspring of
      type 2 diabetic parents without DN (DN-); and (iii) offspring of type 2 diabetic
      parents with DN (DN+). Ambulatory BP and hormones involved in sodium homeostasis
      [plasma renin activity (PRA), aldosterone and atrial natriuretic peptide (ANP)]
      as well as the tetrahydrocortisol + 5-allotetrahydrocortisol/tetrahydrocortisone
      (THF + 5alphaTHF)/THE) ratio in the urine as an index of 11beta-hydroxysteroid
      dehydrogenase type 2 (11betaHSD2) activity were analysed. RESULTS: In offspring
      of DN+ patients on a high salt diet, systolic and diastolic BP was 137/82+/-10/8
      mmHg vs 125/77+/-12/8 mmHg in offspring of DN- patients (P<0.01 for systolic BP).
      The salt-induced difference in mean BP between high and low salt diet was 5.2+/
      3.3 mmHg in offspring of DN+ patients vs 0.7+/-4.7 mmHg in offspring of DN-
      patients (P<0.002). The proportion of 'salt-sensitive' individuals was 67% in
      offspring of DN+ patients vs 20% in offspring of DN- patients (P<0.05). In all
      groups, a high salt diet caused a comparable decrease of PRA and p-aldosterone
      accompanied by an increase in ANP. The urinary (THF + 5alphaTHF)/THE ratio was
      1.23+/-0.36 in salt-sensitive individuals and 0.99+/-0.33 (P<0.03) in salt
      resistant subjects, consistent with increased activity of 11betaHSD2.
      CONCLUSIONS: BP is more salt sensitive in offspring of type 2 diabetic patients
      with diabetic nephropathy. The salt sensitivity of BP may be an intermediate
      phenotype in individuals with a high risk of future diabetic nephropathy.

PMID- 15870225
TI  - Role of atrophic changes in proximal tubular cells in the peritubular deposition
      of type IV collagen in a rat renal ablation model.
AB  - BACKGROUND: Tubular atrophy, dilation and interstitial fibrosis are common in
      tubulointerstitial lesions, but the precise roles and inter-relationships of
      these components in the development of interstitial lesions have not been
      determined. This study focused on the origin and roles of atrophic tubules in the
      peritubular deposition of type IV collagen in a rat renal ablation model.
      METHODS: Male Wistar rats underwent 5/6 nephrectomy or sham operation, and then
      were sacrificed at 4, 8 or 12 weeks, their remaining kidneys removed for
      histological and immuno-histochemical studies as well as in situ hybridization
      for type IV collagen mRNA. RESULTS: Immuno-histochemistry demonstrated the
      positive staining of atrophic tubules to vimentin, platelet-derived growth factor
      B chain (PDGF) and heat shock protein 47 (HSP47). Cells positive to one or more
      of PDGF receptor beta, alpha-smooth muscle actin (alpha-SMA), and HSP47
      accumulated around atrophic tubules. Type IV collagen was also increased in the
      proximity of the atrophic tubules. These intimate relationships were more clearly
      demonstrated in 'mosaic tubules', which are composed of both intact and atrophic
      proximal tubular epithelial cells, and which had a mixed pattern of staining with
      vimentin, PDGF and HSP47. The interstitial cells positive to alpha-SMA or HSP47,
      or both, were in close contact with atrophic but not with intact epithelial
      cells. Type IV collagen was exclusively deposited between atrophic tubules and
      HSP47-positive interstitial cells. In situ hybridization of type IV collagen mRNA
      demonstrated predominant expression in atrophic tubular epithelial cells, but not
      in surrounding interstitial cells. CONCLUSIONS: These findings suggest that
      atrophic proximal tubular cells are active in the development of collagen
      deposition in the peritubular space, i.e. in this model type IV collagen in the
      interstitial fibrotic area may be produced mainly by atrophic proximal tubules.

PMID- 15870226
TI  - Using geographical information systems to plan dialysis facility provision.

PMID- 15870227
TI  - Severe early acute humoral rejection resulting in allograft loss in a renal
      transplant recipient with Campath-1H induction therapy.

PMID- 15870228
TI  - Transjugular renal biopsy. Update on hepato-renal needlework.

PMID- 15870229
TI  - A mouse model of ethanol dependent pancreatic fibrosis.
AB  - BACKGROUND AND AIMS: The majority of patients with chronic pancreatitis are
      alcoholics. Our goal was to develop a mouse model of alcohol dependent chronic
      pancreatitis. METHODS: Mice were fed either the non-alcohol containing Lieber
      DeCarli diet or the Lieber-DeCarli diet containing 24% of calories as ethanol.
      After eight weeks and while on their respective diets, mice were subjected to
      repeated episodes of acute pancreatitis elicited by administration of caerulein.
      They were sacrificed 1, 3, and 5 weeks after the last dose of caerulein.
      Pancreatic morphology and collagen deposition were evaluated in samples stained
      with haematoxylin-eosin and Sirius red. Collagen content was quantitated by
      measuring OH-proline. Gene expression was determined by quantitative polymerase
      chain reaction. RESULTS: Both groups of mice gained weight at the same rate.
      Those receiving the alcohol containing diet had serum alcohol levels of
      approximately 100 mM. No histological or gene expression differences were found
      in mice that were not subjected to acute pancreatitis, regardless of their diet.
      Necrosis, Sirius red staining, OH-proline content, and expression of alpha-1
      collagen I, alpha-smooth muscle actin, transforming growth factor beta1, and
      tissue inhibitor of metalloproteinase 1 were all increased in mice fed the
      alcohol containing diet and given caerulein compared with those fed the control
      diet and given caerulein. Matrix metalloproteinase 9 expression was transiently
      decreased in mice fed ethanol and given caerulein compared with the group given
      caerulein but not fed ethanol. CONCLUSION: We have developed a mouse model of
      alcohol dependent chronic pancreatic fibrosis. This mouse model may be useful in
      studies examining the effects of genetic manipulation on chronic pancreatitis.

PMID- 15870230
TI  - Methylation of the oestrogen receptor gene in non-neoplastic epithelium as a
      marker of colorectal neoplasia risk in longstanding and extensive ulcerative
      colitis.
AB  - BACKGROUND: Surveillance colonoscopy is widely recommended in patients with
      longstanding and extensive ulcerative colitis (UC) in order to detect colorectal
      neoplasia at an early stage. However, it still remains questionable whether
      surveillance colonoscopy effectively enables early detection of UC associated
      neoplasia. There is a great need for sensitive markers to identify individuals at
      increased risk of neoplasia. The oestrogen receptor (OR) gene shows age related
      methylation in the colorectal epithelium and is methylated frequently in sporadic
      colorectal neoplasia, suggesting that OR methylation may predispose to colorectal
      neoplasia. AIM: To clarify whether analysis of methylation of the OR gene in non
      neoplastic epithelium can contribute to prediction of increased neoplasia risk in
      UC patients. MATERIALS AND METHODS: A total of 165 non-neoplastic colorectal
      epithelia from 30 patients with longstanding and extensive UC, including 13 UC
      patients with neoplasia and 17 patients without, were evaluated. Methylation
      specific polymerase chain reaction was performed to determine the methylation
      status of the OR gene. RESULTS: Methylation of the OR gene was detected in 54 of
      70 (77.1%) non-neoplastic colorectal epithelia in UC with neoplasia but in only
      23 of 95 (24.2%) without neoplasia. Methylation of the OR gene was significantly
      more frequent in non-neoplastic epithelium from UC with neoplasia than in chronic
      colitic epithelium from UC without neoplasia. Furthermore, in UC with neoplasia,
      the OR gene was extensively methylated in non-neoplastic epithelia throughout the
      colorectum compared with those in UC without neoplasia. CONCLUSION: These results
      suggest that analysis of OR gene methylation may have potential as a useful
      marker for identifying individuals at increased risk of neoplasia among those
      with longstanding and extensive UC.

PMID- 15870232
TI  - The Japanese Academy of Nursing Science.

PMID- 15870231
TI  - Anti-inflammatory effects of pancreatitis associated protein in inflammatory
      bowel disease.
AB  - BACKGROUND AND AIMS: Increased pancreatitis associated protein (PAP) mRNA has
      been reported in active inflammatory bowel disease (IBD). The aims of the current
      study were to characterise PAP production in IBD and the effects of PAP on
      inflammation. PATIENTS AND METHODS: Serum PAP levels were determined in healthy
      controls (n = 29), inflammatory controls (n = 14), and IBD patients (n = 171). Ex
      vivo PAP secretion in intestinal tissue was measured in 56 IBD patients and 13
      healthy controls. Cellular origin of PAP was determined by immunohistochemistry.
      The effects of exogenous PAP on nuclear factor kappaB (NFkappaB) activation,
      proinflammatory cytokine production, and endothelial adhesion molecule expression
      were also analysed ex vivo. RESULTS: Patients with active IBD had increased serum
      PAP levels compared with controls, and these levels correlated with clinical and
      endoscopic disease severity. Ex vivo intestinal PAP synthesis was increased in
      active IBD and correlated with endoscopic and histological severity of
      inflammatory lesions. PAP localised to colonic Paneth cells. Incubation of mucosa
      from active Crohn's disease with PAP dose dependently reduced proinflammatory
      cytokines secretion. PAP prevented TNF-alpha induced NFkappaB activation in
      monocytic, epithelial, and endothelial cells and reduced proinflammatory cytokine
      mRNA levels and adhesion molecule expression. CONCLUSIONS: PAP is synthesised by
      Paneth cells and is overexpressed in colonic tissue of active IBD. PAP inhibits
      NFkappaB activation and downregulates cytokine production and adhesion molecule
      expression in inflamed tissue. It may represent an anti-inflammatory mechanism
      and new therapeutic strategy in IBD.

PMID- 15870233
TI  - Mitral valve prolapse syndrome health concerns, symptoms, and treatments.
AB  - Individuals with mitral valve prolapse syndrome (MVPS) symptoms seek help in
      emergency rooms, urgent care centers, and primary care offices. Little is known
      about the profile and effects of these symptoms on individuals' role status and
      use of health care services. A descriptive cross-sectional design was used to
      develop a profile of health concerns, symptoms, and treatments and to examine the
      relationships of symptoms to functional and role status and use of health care
      services for MVPS patients. A sample of 837 persons completed an MVPS symptom
      checklist and survey, Mishel Uncertainty Illness Scale, Short Form Health Survey,
      State-Trait Anxiety Inventory, Medical Outcomes Study Social Support, and Food
      Frequency Questionnaire. Descriptive statistics, multiple-regression analysis,
      and structural equation modeling were used to answer the research questions.
      Findings suggest that older age, lack of social support, higher anxiety, and lack
      of regular exercise predict MVPS symptoms. There was limited support for the
      overall theoretical model.

PMID- 15870236
TI  - Smoking cessation strategy use among pregnant ex-smokers.
AB  - There is strong evidence for the beneficial health effects associated with
      smoking cessation during pregnancy. Although many pregnant women spontaneously
      quit smoking during pregnancy, postpartum relapse is high. Evidence suggests that
      pregnant women do not use smoking cessation strategies as identified by the 40
      item Processes of Change Scale as frequently as others who quit smoking. The
      purpose of this study is to identify factors associated with pregnant exsmokers'
      use of experiential and behavioral smoking cessation strategies. A cross
      sectional survey design is used for the study. From a sample of 201 primarily low
      income pregnant women recruited to participate in a larger study, 58 were
      biologically confirmed ex-smokers. Multiple regression analysis reveals that
      motivation to quit smoking is the only significant factor explaining the use of
      experiential and behavioral smoking cessation strategies, accounting for 44% of
      the variance in experiential processes and 31% of the variance in behavioral
      processes.

PMID- 15870240
TI  - Developing a cultural model of caregiving obligations for elderly Chinese wives.
AB  - This article addresses the dilemmas of elderly Chinese women as spousal
      caregivers in Hong Kong in the 1990s. An in-depth ethnographic approach was used
      to draw on a convenience sample of 20 elderly wives who were caregivers from Hong
      Kong. At the conceptual level, the discussion highlights how caregiving is rooted
      in complex, culturally-based models of contemporary practices, sociohistoric
      patterns, and gender-specific obligations. The key themes identified were marital
      duty-bound roles and responsibilities, reciprocity and burden, public guidelines
      and upholding reputations as Chinese wives, monetary restrictions, affection as
      an emotional force to sustain caregiving, effects of the caregiving role, and the
      creation of self-identity through caregiving. The model proposed for interpreting
      elderly Chinese wives' caregiving obligations highlights the tension-filled links
      between Confucianism and government guidelines, early and ongoing socializing
      experiences, and self-identity.

PMID- 15870244
TI  - Access to health services by Canadians who are chronically ill.
AB  - Access to health care services in Canada has been identified as an urgent
      priority, and chronic disease has been suggested as the most pressing health
      concern facing Canadians. Access to services for Canadians living with chronic
      disease, however, has received little emphasis in the research literature or in
      health policy reform documents. A systematic review of research into factors
      impeding or facilitating access to formal health services for people in Canada
      living with chronic illness is presented. The review includes 31 studies of
      Canadian populations published between 1990 and 2002; main results were analyzed
      for facilitators and barriers to access for people experiencing chronic disease.
      An underlying organizing construct of symmetry between consumers, providers, and
      the larger Canadian system is suggested as a relevant lens from which to view the
      findings. Finally, a discussion of the relationship between identified factors
      and the principles of primary health care is offered.

PMID- 15870245
TI  - Ethical issues faced by nursing editors.
AB  - This study reports on ethical issues faced by editors of nursing journals, a
      topic which has not appeared in the nursing literature. A survey of nursing
      editors (n = 88)was conducted via e-mail; this article is the content analysis of
      survey questions about ethics. Eight categories of ethical issues emerged:
      problems with society/association/publisher; decisions about inflammatory
      submissions; informed consent or IRB issues; conflicts of interest; advertising
      pressures; duplicate publications and/or plagiarism; difficult interactions with
      authors; and authorship. Some issues were similar to those published about
      medical editors; however, others were unique. This study can assist authors to
      better understand some of the ethical issues in publishing, can help editors to
      view their issues in the context of what others experience, and can assist
      societies and publishers to work toward avoiding these ethical issues in the
      future. Professional discussions about ethics in nursing publications should be
      the subject of ongoing research and scientific inquiry.

PMID- 15870246
TI  - Modeling ADHD child and family relationships.
AB  - Little information is available on how to help families manage common negative
      sequelae of attention deficit/hyperactivity disorder (ADHD). This article is a
      report of the extent to which a theoretical formulation of child behavior,
      maternal distress, and family conflict was explained by data obtained from a
      community sample of families with children and adolescents with ADHD. Structural
      equation modeling was used to test the theoretical model. The primary variables
      of interest were (a) child behavior problems, (b) maternal distress, and (c)
      family conflict. The results suggest that maternal distress may mediate the
      relationship between child behavior problems and family conflict, indicating the
      critical importance of mothers in ADHD families and the need to provide them with
      additional support.

PMID- 15870247
TI  - Use of the D-dimer assay for diagnosing thromboembolic disease in the dog.
AB  - Although the exact incidence of pulmonary thromboembolism (PTE) in small animals
      is unknown, it is thought that PTE is a substantial, under-diagnosed
      complication. The difficulty in diagnosing PTE in small animals is confounded by
      its subtle symptomatic presentation and a lack of clinical suspicion, coexisting
      disease states, and lack of noninvasive tests that are sensitive and specific for
      the diagnosis of PTE. Although numerous laboratory markers of coagulation have
      been studied, only the D-dimer assay has shown clinical utility in detecting
      early embolism in humans. This paper examines the use of D-dimer assays and other
      clinical modalities in the diagnostic approach to thromboembolic disease in small
      animals.

PMID- 15870248
TI  - Methicillin-resistant Staphylococcus aureus: an emerging pathogen in small
      animals.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial
      pathogen in humans and is increasingly implicated in community-associated
      infections in people. In household pets, MRSA infections are uncommon but are on
      the rise, possibly because of the increased prevalence of human MRSA in the
      community. Clinical MRSA infections in some animals can be life threatening and
      difficult to treat; however, other animals may develop mild disease or only
      become colonized. Veterinarians should be aware of the concerns regarding MRSA
      and should develop an understanding of appropriate disease surveillance,
      diagnostic testing, and infection control in order to lessen the impact of MRSA
      on small animals.

PMID- 15870249
TI  - Spontaneous chronic corneal epithelial defects in dogs: a review.
AB  - Spontaneous chronic corneal epithelial defects (SCCEDs) in dogs are typically
      found in middle-aged dogs of all breeds. These epithelial defects may be present
      for weeks to months, particularly if left untreated or if treated
      inappropriately. Typical histopathological findings include loss of the corneal
      epithelial basement membrane and formation of a superficial, acellular,
      hyalinized zone in the stroma. Together, these histological abnormalities lead to
      delayed wound healing and poor epithelial adhesion. Epithelial debridement,
      anterior stromal puncture, grid keratotomy, and superficial keratectomy are the
      most common treatment options applied to the defects. Procedures that address the
      stromal changes present generally have a higher success rate than epithelial
      debridement alone.

PMID- 15870250
TI  - Simultaneous bilateral femoral head and neck ostectomy for the treatment of
      canine hip dysplasia.
AB  - Simultaneous bilateral femoral head and neck ostectomy (FHO) was performed on 15
      dogs for severe bilateral hip dysplasia. A follow-up survey was performed 6 to 48
      months after surgery to assess the postoperative recovery and activity levels of
      the operated dogs. All dogs had normal activity levels and were pain free
      according to their owners. Owner satisfaction regarding the outcome of the
      surgery was high. Simultaneous bilateral FHO was a viable surgical option for the
      treatment of painful bilateral hip disease in dogs, especially when other
      surgical options were not indicated or were cost prohibitive.

PMID- 15870251
TI  - Clinical utility of pneumogastrography in dogs.
AB  - Pneumogastrography utilizes negative contrast media such as air or carbonated
      beverages to improve visualization of luminal contents and mucosal surfaces
      within the stomach. Pneumogastrography as a diagnostic technique in cases of
      gastric disease has not been widely described in the veterinary literature and is
      a procedure that may yield additional information not obtained from survey
      radiographs. This technique is useful in the diagnosis of luminal and mucosal
      gastric diseases. In this article, the pneumogastrography technique and relevant
      literature are reviewed. Six case examples are included that demonstrate the
      utility of pneumogastrography in dogs with gastric disease.

PMID- 15870252
TI  - Clinical features of epistaxis in dogs: a retrospective study of 35 cases (1999
      2002).
AB  - Epistaxis was retrospectively evaluated in 35 dogs. Systemic disease was
      diagnosed in seven dogs and intranasal disease in 29. Nineteen dogs with
      intranasal disease had neoplasia. Dogs with neoplasia were older (mean 10.0
      years) than dogs with nonneoplastic intranasal disease (mean 5.6 years). Signs
      persisting for >1 month occurred more often in dogs with intranasal than systemic
      disease. Unilateral epistaxis did not distinguish intranasal from systemic
      disease. Only dogs with intranasal disease had facial deformity, decreased
      airflow, or regional sub-mandibular lymphadenopathy. Dogs with systemic disease
      had a lower packed cell volume (mean 31.8%) than dogs with intranasal disease
      (mean 42.7%).

PMID- 15870253
TI  - Clinical evaluation of caudal superficial epigastric axial pattern flap
      reconstruction of skin defects in 10 dogs (1989-2001).
AB  - Ten dogs with caudal superficial epigastric axial pattern flap reconstruction of
      extensive skin defects were reviewed. Nine dogs had complete survival of the
      flap. In one dog, a small area of necrosis occurred near the flap tip. Other
      complications included seroma formation (n=3), partial incisional dehiscence
      (n=3), flap edema (n=9), and bruising (n=7). Use of the caudal superficial
      epigastric axial pattern flap provided full-thickness skin coverage of extensive
      skin defects of the rear limb and inguinal region, with relatively minor
      complications that were amenable to conservative management.

PMID- 15870254
TI  - Suspected iatrogenic paradoxical embolization in a cat.
AB  - A cat was evaluated for a 5-year history of progressive, episodic, exercise
      induced cyanosis and panting. Diagnostic testing demonstrated tetralogy of Fallot
      with predominant right-to-left shunting and right-sided heart failure. Following
      diagnostic catheterization, the cat developed clinical signs consistent with
      systemic arterial thromboembolization and was euthanized. Necropsy findings
      included multiple thrombi within the right atrium and ventricle, and
      thromboemboli within the terminal aorta and right common carotid artery, a
      condition most consistent with iatrogenic paradoxical embolization secondary to
      diagnostic catheterization. Paradoxical embolization and thromboembolic
      complications of diagnostic catheterization are discussed.

PMID- 15870255
TI  - Cutaneous manifestations of disseminated toxoplasmosis in an immunosuppressed
      dog.
AB  - A 3.5-year-old, castrated male, giant schnauzer was presented with alopecic
      pustular dermatitis. Immune-mediated hemolytic anemia had been diagnosed 45 days
      previously. At the time of presentation, the dog was receiving prednisone,
      azathioprine, and cyclosporine. Cutaneous protozoosis was diagnosed, and
      postmortem examination revealed protozoa within cutaneous, cardiac, pancreatic,
      and pulmonary tissues. The protozoa divided by endodyogeny, had the morphology of
      Toxoplasma gondii (T. gondii) tachyzoites, and stained positively with T. gondii
      polyclonal antibodies but not with antibodies to Neospora caninum or Sarcocystis
      neurona. Immunosuppression may have predisposed this dog to disseminated
      toxoplasmosis.

PMID- 15870256
TI  - Use of a new investigational interlocking nail supplement in the repair of
      comminuted diaphyseal tibia fractures in two dogs.
AB  - Two dogs were diagnosed with highly comminuted diaphyseal tibial fractures
      following traumatic incidents. Investigational hybrid interlocking nail (ILN)
      bolt/external skeletal fixator (ESF) pins were used to repair both fractures. The
      surgery was successful, and fractures healed without complications by 6 weeks
      (case no. 1) and 17 weeks (case no. 2) after surgery. This article describes the
      application and the advantages of a new, investigational ILN supplement that was
      specifically designed to accomplish initial rigid stability and allow progressive
      destabilization to the fracture repair. The authors are continuing to study the
      biomechanical properties of this procedure in order to accurately establish clear
      recommendations for its use in certain fracture situations.

PMID- 15870257
TI  - PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints.
AB  - The ATM (ataxia-telangiectasia mutated) and ATR (ataxia-telangiectasia and Rad3
      related) kinases respond to DNA damage by phosphorylating cellular target
      proteins that activate DNA repair pathways and cell cycle checkpoints in order to
      maintain genomic integrity. Here we show that the oncogenic p53-induced
      serine/threonine phosphatase, PPM1D (or Wip1), dephosphorylates two ATM/ATR
      targets, Chk1 and p53. PPM1D binds Chk1 and dephosphorylates the ATR-targeted
      phospho-Ser 345, leading to decreased Chk1 kinase activity. PPM1D also
      dephosphorylates p53 at phospho-Ser 15. PPM1D dephosphorylations are correlated
      with reduced cellular intra-S and G2/M checkpoint activity in response to DNA
      damage induced by ultraviolet and ionizing radiation. Thus, a primary function of
      PPM1D may be to reverse the p53 and Chk1-induced DNA damage and cell cycle
      checkpoint responses and return the cell to a homeostatic state following
      completion of DNA repair. These homeostatic functions may be partially
      responsible for the oncogenic effects of PPM1D when it is amplified and
      overexpressed in human tumors.

PMID- 15870258
TI  - p38 MAP kinase inhibition enables proliferation of adult mammalian
      cardiomyocytes.
AB  - Adult mammalian cardiomyocytes are considered terminally differentiated and
      incapable of proliferation. Consequently, acutely injured mammalian hearts do not
      regenerate, they scar. Here, we show that adult mammalian cardiomyocytes can
      divide. One important mechanism used by mammalian cardiomyocytes to control cell
      cycle is p38 MAP kinase activity. p38 regulates expression of genes required for
      mitosis in cardiomyocytes, including cyclin A and cyclin B. p38 activity is
      inversely correlated with cardiac growth during development, and its
      overexpression blocks fetal cardiomyocyte proliferation. Activation of p38 in
      vivo by MKK3bE reduces BrdU incorporation in fetal cardiomyocytes by 17.6%. In
      contrast, cardiac-specific p38alpha knockout mice show a 92.3% increase in
      neonatal cardiomyocyte mitoses. Furthermore, inhibition of p38 in adult
      cardiomyocytes promotes cytokinesis. Finally, mitosis in adult cardiomyocytes is
      associated with transient dedifferentiation of the contractile apparatus. Our
      findings establish p38 as a key negative regulator of cardiomyocyte proliferation
      and indicate that adult cardiomyocytes can divide.

PMID- 15870259
TI  - RNA-guided RNA modification: functional organization of the archaeal H/ACA RNP.
AB  - In eukaryotes and archaea, uridines in various RNAs are converted to
      pseudouridines by RNA-guided RNA modification complexes termed H/ACA RNPs. Guide
      RNAs within the complexes base-pair with target RNAs to direct modification of
      specific ribonucleotides. Cbf5, a protein component of the complex, likely
      catalyzes the modification. However, little is known about the organization of
      H/ACA RNPs and the roles of the multiple proteins thought to comprise the
      complexes. We have reconstituted functional archaeal H/ACA RNPs from recombinant
      components, defined the components necessary and sufficient for function, and
      determined the direct RNA-protein and protein-protein interactions that occur
      between the components. The results provide substantial insight into the
      functional organization of this RNP. The functional complex requires a guide RNA
      and each of four proteins: Cbf5, Gar1, L7Ae, and Nop10. Two proteins interact
      directly with the guide RNA: L7Ae and Cbf5. L7Ae does not interact with other
      H/ACA RNP proteins in the absence of the RNA. We have defined two novel functions
      for Cbf5. Cbf5 is the protein that specifically recognizes and binds H/ACA guide
      RNAs. In addition, Cbf5 recruits the two other essential proteins, Gar1 and
      Nop10, to the pseudouridylation guide complex.

PMID- 15870260
TI  - Functional characterization of a novel Ku70/80 pause site at the H19/Igf2
      imprinting control region.
AB  - The imprinted expression of the H19 and Igf2 genes in the mouse is controlled by
      an imprinting control center (ICR) whose activity is regulated by parent-of
      origin differences in methylation. The only protein that has been implicated in
      ICR function is the zinc-finger protein CTCF, which binds at multiple sites
      within the maternally inherited ICR and is required to form a chromatin boundary
      that inhibits Igf2 expression. To identify other proteins that play a role in
      imprinting, we employed electrophoresis mobility shift assays to identify two
      novel binding sites within the ICR. The DNA binding activity was identified as
      the heterodimer Ku70/80, which binds nonspecifically to free DNA ends. The sites
      within the ICR bind Ku70/80 in a sequence-specific manner and with higher
      affinity than previously reported binding sites. The binding required the
      presence of Mg(2+), implying that the sequence is a pause site for Ku70/80
      translocation from a free end. Chromatin immunoprecipitation assays were unable
      to confirm that Ku70/80 binds to the ICR in vivo. In addition, mutation of these
      binding sites in the mouse did not result in any imprinting defects. A genome
      scan revealed that the binding site is found in LINE-1 retrotransposons,
      suggesting a possible role for Ku70/80 in transposition.

PMID- 15870261
TI  - The human beta-globin locus control region can silence as well as activate gene
      expression.
AB  - Using recombinase-mediated cassette exchange to test multiple transgenes at the
      same site of integration, we demonstrate a novel chromatin context-dependent
      silencer activity of the beta-globin locus control region (LCR). This silencer
      activity requires DNase I hypersensitive sites HS2 and HS3 but not HS4. After
      silencing, the silenced cassettes adopt a typical closed chromatin conformation
      (histone H3 and H4 deacetylation, histone H3-K4 methylation, DNA methylation, and
      replication in late S phase). In the absence of the LCR at the same site of
      integration, the chromatin remains decondensed. We demonstrate that the LCR is
      necessary but not sufficient to trigger these chromatin changes. We also provide
      evidence that this novel silencing activity is caused by transcriptional
      interference triggered by activation of transcription in the flanking sequences
      by the LCR.

PMID- 15870262
TI  - The F-box protein Met30 is required for multiple steps in the budding yeast cell
      cycle.
AB  - The Saccharomyces cerevisiae ubiquitin ligase SCF(Met30) is essential for cell
      cycle progression. To identify and characterize SCF(Met30)-dependent cell cycle
      steps, we used temperature-sensitive met30 mutants in cell cycle synchrony
      experiments. These experiments revealed a requirement for Met30 during both
      G(1)/S transition and M phase, while progression through S phase was unaffected
      by loss of Met30 function. Expression of the G(1)-specific transcripts CLN1,
      CLN2, and CLB5 was very low in met30 mutants, whereas expression of CLN3 was
      unaffected. However, overexpression of Cln2 could not overcome the G(1) arrest.
      Interestingly, overexpression of Clb5 could induce DNA replication in met30
      mutants, albeit very inefficiently. Increased levels of Clb5 could not, however,
      suppress the cell proliferation defect of met30 mutants. Consistent with the DNA
      replication defects, chromatin immunoprecipitation experiments revealed
      significantly lower levels of the replication factors Mcm4, Mcm7, and Cdc45 at
      replication origins in met30 mutants than in wild-type cells. These data suggest
      that Met30 regulates several aspects of the cell cycle, including G(1)-specific
      transcription, initiation of DNA replication, and progression through M phase.

PMID- 15870263
TI  - Regulation of the deubiquitinating enzyme CYLD by IkappaB kinase gamma-dependent
      phosphorylation.
AB  - Tumor suppressor CYLD is a deubiquitinating enzyme (DUB) that inhibits the
      ubiquitination of key signaling molecules, including tumor necrosis factor (TNF)
      receptor-associated factor 2 (TRAF2). However, how the function of CYLD is
      regulated remains unknown. Here we provide evidence that inducible
      phosphorylation of CYLD is an important mechanism of its regulation. Under normal
      conditions, CYLD dominantly suppresses the ubiquitination of TRAF2. In response
      to cellular stimuli, CYLD undergoes rapid and transient phosphorylation, which is
      required for signal-induced TRAF2 ubiquitination and activation of downstream
      signaling events. Interestingly, the CYLD phosphorylation requires IkappaB kinase
      gamma (IKKgamma) and can be induced by IKK catalytic subunits. These findings
      suggest that CYLD serves as a novel target of IKK and that the site-specific
      phosphorylation of CYLD regulates its signaling function.

PMID- 15870264
TI  - Efficiency of RNA interference in the mouse hematopoietic system varies between
      cell types and developmental stages.
AB  - RNA interference (RNAi) is a naturally occurring posttranscriptional gene
      silencing mechanism that has been adapted as a genetic tool for loss-of-function
      studies of a variety of organisms. It is more widely applicable than classical
      gene targeting and allows for the simultaneous inactivation of several homologous
      genes with a single transgene. Recently, RNAi has been used for conditional and
      conventional gene inactivation in mice. Unlike gene targeting, RNAi is a dynamic
      process, and its efficiency may vary both between cell types and throughout
      development. Here we demonstrate that RNAi can be used to target three separately
      encoded isoforms of the bcl-2 family gene bfl-1/A1 in a conditional manner in
      mice. The extent of gene inactivation varies between different cell types and is
      least efficient in mature lymphocytes. Our data suggest that RNAi is affected by
      factors beyond small interfering RNA-mRNA stoichiometry.

PMID- 15870265
TI  - Phosphorylation by Cak1 regulates the C-terminal domain kinase Ctk1 in
      Saccharomyces cerevisiae.
AB  - Ctk1 is a Saccharomyces cerevisiae cyclin-dependent protein kinase (CDK) that
      assembles with Ctk2 and Ctk3 to form an active protein kinase complex, CTDK-I.
      CTDK-I phosphorylates Ser2 within the RNA polymerase II C-terminal domain, an
      activity that is required for efficient transcriptional elongation and 3' RNA
      processing. Ctk1 contains a conserved T loop, which undergoes activating
      phosphorylation in other CDKs. We show that Ctk1 is phosphorylated on Thr-338
      within the T loop. Mutation of this residue abolished Ctk1 kinase activity in
      vitro and resulted in a cold-sensitive phenotype. As with other yeast CDKs
      undergoing T-loop phosphorylation, Ctk1 phosphorylation on Thr-338 was dependent
      on the Cak1 protein kinase. Ctk1 isolated from cak1Delta cells was
      unphosphorylated and exhibited low protein kinase activity. Moreover, Cak1
      directly phosphorylated Ctk1 in vitro. Unlike wild-type cells, cells expressing
      Ctk1(T338A) delayed growth at early stationary phase, did not show the increase
      in Ser2 phosphorylation that normally accompanies the transition from rapid
      growth to stationary phase, and had compromised transcriptional activation of two
      stationary-phase genes, CTT1 and SPI1. Therefore, Ctk1 phosphorylation on Thr-338
      is carried out by Cak1 and is required for normal gene transcription during the
      transition into stationary phase.

PMID- 15870266
TI  - The H1 phosphorylation state regulates expression of CDC2 and other genes in
      response to starvation in Tetrahymena thermophila.
AB  - In Tetrahymena thermophila, highly phosphorylated histone H1 of growing cells
      becomes partially dephosphorylated when cells are starved in preparation for
      conjugation. To determine the effects of H1 phosphorylation on gene expression,
      PCR-based subtractive hybridization was used to clone cDNAs that were
      differentially expressed during starvation in two otherwise-isogenic strains
      differing only in their H1s. H1 in A5 mutant cells lacked phosphorylation, and H1
      in E5 cells mimicked constitutive H1 phosphorylation. Sequences enriched in A5
      cells included genes encoding proteases. Sequences enriched in E5 cells included
      genes encoding cdc2 kinase and a Ser/Thr kinase. These results indicate that H1
      phosphorylation plays an important role in regulating the pattern of gene
      expression during the starvation response and that its role in transcription
      regulation can be either positive or negative. Treatment of starved cells with a
      phosphatase inhibitor caused CDC2 gene overexpression. Expression of the E5
      version of H1 in starved cells containing endogenous, wild-type H1 caused the
      wild-type H1 to remain highly phosphorylated. These results argue that Cdc2p is
      the kinase that phosphorylates Tetrahymena H1, establish a positive feedback
      mechanism between H1 phosphorylation and CDC2 expression, and indicate that CDC2
      gene expression is regulated by an H1 phosphatase.

PMID- 15870267
TI  - Chromatin inactivation precedes de novo DNA methylation during the progressive
      epigenetic silencing of the RASSF1A promoter.
AB  - Epigenetic inactivation of the RASSF1A tumor suppressor by CpG island methylation
      was frequently detected in cancer. However, the mechanisms of this aberrant DNA
      methylation are unknown. In the RASSF1A promoter, we characterized four Sp1
      sites, which are frequently methylated in cancer. We examined the functional
      relationship between DNA methylation, histone modification, Sp1 binding, and
      RASSF1A expression in proliferating human mammary epithelial cells. With
      increasing passages, the transcription of RASSF1A was dramatically silenced. This
      inactivation was associated with deacetylation and lysine 9 trimethylation of
      histone H3 and an impaired binding of Sp1 at the RASSF1A promoter. In mammary
      epithelial cells that had overcome a stress-associated senescence barrier, a
      spreading of DNA methylation in the CpG island promoter was observed. When the
      RASSF1A-silenced cells were treated with inhibitors of DNA methyltransferase and
      histone deacetylase, binding of Sp1 and expression of RASSF1A reoccurred. In
      summary, we observed that histone H3 deacetylation and H3 lysine 9 trimethylation
      occur in the same time window as gene inactivation and precede DNA methylation.
      Our data suggest that in epithelial cells, histone inactivation may trigger de
      novo DNA methylation of the RASSF1A promoter and this system may serve as a model
      for CpG island inactivation of tumor suppressor genes.

PMID- 15870269
TI  - Response of fission yeast to toxic cations involves cooperative action of the
      stress-activated protein kinase Spc1/Sty1 and the Hal4 protein kinase.
AB  - Stress-activated protein kinases (SAPKs), members of a mitogen-activated protein
      kinase (MAPK) subfamily, are highly conserved among eukaryotes. Studies of yeasts
      demonstrated that SAPKs play pivotal roles in survival responses to high
      osmolarity, oxidative stress, and heat shock. Here we report a novel
      physiological role of the fission yeast Spc1 SAPK in cellular resistance to
      certain cations, such as Na(+), Li(+), and Ca(2+). Strains lacking Spc1 or its
      activator, Wis1 MAPK kinase, are hypersensitive to these cations. Spc1 positively
      regulates expression of sod2(+) encoding a Na(+)/H(+) antiporter through Atf1 and
      other transcription factors. In addition, we have identified a novel Spc1
      interacting protein, Hal4, which is highly homologous to the budding yeast
      Sat4/Hal4 protein kinase. Like its budding yeast counterpart, the fission yeast
      Hal4 kinase is essential for cellular resistance to Na(+), Li(+), and Ca(2+). The
      hal4-null phenotype is complemented by overexpression of the Trk1 potassium
      transporter or increased K(+) in the growth medium, suggesting that Hal4 promotes
      K(+) uptake, which consequently increases cellular resistance to other cations.
      Interestingly, the Spc1-Hal4 interaction appears to be required for cellular
      resistance to Ca(2+) but not Na(+) and Li(+). We propose that Spc1 SAPK and Hal4
      kinase cooperatively function to protect cells from the toxic cations.

PMID- 15870268
TI  - The yeast chromatin remodeler RSC complex facilitates end joining repair of DNA
      double-strand breaks.
AB  - Repair of chromosome double-strand breaks (DSBs) is central to cell survival and
      genome integrity. Nonhomologous end joining (NHEJ) is the major cellular repair
      pathway that eliminates chromosome DSBs. Here we report our genetic screen that
      identified Rsc8 and Rsc30, subunits of the Saccharomyces cerevisiae chromatin
      remodeling complex RSC, as novel NHEJ factors. Deletion of RSC30 gene or the C
      terminal truncation of RSC8 impairs NHEJ of a chromosome DSB created by HO
      endonuclease in vivo. rsc30Delta maintains a robust level of homologous
      recombination and the damage-induced cell cycle checkpoints. By chromatin
      immunoprecipitation, we show recruitment of RSC to a chromosome DSB with kinetics
      congruent with its involvement in NHEJ. Recruitment of RSC to a DSB depends on
      Mre11, Rsc30, and yKu70 proteins. Rsc1p and Rsc2p, two other RSC subunits,
      physically interact with yKu80p and Mre11p. The interaction of Rsc1p with Mre11p
      appears to be vital for survival from genotoxic stress. These results suggest
      that chromatin remodeling by RSC is important for NHEJ.

PMID- 15870270
TI  - The LIM protein Ajuba regulates phosphatidylinositol 4,5-bisphosphate levels in
      migrating cells through an interaction with and activation of PIPKI alpha.
AB  - The phosphoinositide phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] regulates
      the activity of many actin-binding proteins and as such is an important modulator
      of cytoskeleton organization during cell migration, for example. In migrating
      cells actin remodeling is tightly regulated and localized; therefore, how the
      PI(4,5)P2 level is spatially and temporally regulated is crucial to understanding
      how it controls cell migration. Here we show that the LIM protein Ajuba
      contributes to the cellular regulation of PI(4,5)P2 levels by interacting with
      and activating the enzymatic activity of the PI(4)P 5-kinase (PIPKIalpha), the
      predominant enzyme in the synthesis of PI(4,5)P2, in a migration stimulus
      regulated manner. In migrating primary mouse embryonic fibroblasts (MEFs) from
      Ajuba(-/-) mice the level of PI(4,5)P2 was decreased with a corresponding
      increase in the level of the substrate PI(4)P. Reintroduction of Ajuba into these
      cells normalized PI(4,5)P2 levels. Localization of PI(4,5)P2 synthesis and
      PIPKIalpha in the leading lamellipodia and membrane ruffles, respectively, of
      migrating Ajuba(-/-) MEFs was impaired. In vitro, Ajuba dramatically activated
      the enzymatic activity of PIPKIalpha while inhibiting the activity of PIPKIIbeta.
      Thus, in addition to its effects upon Rac activity Ajuba can also influence cell
      migration through regulation of PI(4,5)P2 synthesis through direct activation of
      PIPKIalpha enzyme activity.

PMID- 15870271
TI  - CENP-A is required for accurate chromosome segregation and sustained kinetochore
      association of BubR1.
AB  - CENP-A is an evolutionarily conserved, centromere-specific variant of histone H3
      that is thought to play a central role in directing kinetochore assembly and in
      centromere function. Here, we have analyzed the consequences of disrupting the
      CENP-A gene in the chicken DT40 cell line. In CENP-A-depleted cells, kinetochore
      protein assembly is impaired, as indicated by mislocalization of the inner
      kinetochore proteins CENP-I, CENP-H, and CENP-C as well as the outer components
      Nuf2/Hec1, Mad2, and CENP-E. However, BubR1 and the inner centromere protein
      INCENP are efficiently recruited to kinetochores. Following CENP-A depletion,
      chromosomes are deficient in proper congression on the mitotic spindle and there
      is a transient delay in prometaphase. CENP-A-depleted cells further proceed
      through anaphase and cytokinesis with unequal chromosome segregation, suggesting
      that some kinetochore function remains following substantial depletion of CENP-A.
      We furthermore demonstrate that CENP-A-depleted cells exhibit a specific defect
      in maintaining kinetochore localization of the checkpoint protein BubR1 under
      conditions of checkpoint activation. Our data thus point to a specific role for
      CENP-A in assembly of kinetochores competent in the maintenance of mitotic
      checkpoint signaling.

PMID- 15870272
TI  - Negative feedback regulation of Met-dependent invasive growth by Notch.
AB  - The hepatocyte growth factor (HGF) receptor encoded by the Met oncogene controls
      a genetic program-known as "invasive growth"-responsible for several
      developmental processes and involved in cancer invasion and metastasis. This
      program functions through several regulatory gene products, as yet largely
      unknown, both upstream and downstream of Met. Here we show that activation of the
      Notch receptor results in transcriptional down-regulation of Met, suppression of
      HGF-dependent Ras signaling, and impairment of HGF-dependent cellular responses.
      In turn, Met activation leads to transcriptional induction of the Notch ligand
      Delta and the Notch effector HES-1, indicating that Met is able to self-tune its
      own protein levels and the ensuing biochemical and biological outputs through
      stimulation of the Notch pathway. By using branching morphogenesis of the
      tracheal system in Drosophila as a readout of invasive growth, we also show that
      exogenous expression of a constitutively active form of human Met induces
      enhanced sprouting of the tracheal tree, a phenotype that is further increased in
      embryos lacking Notch function. These results unravel an in-built mechanism of
      negative feedback regulation in which Met activation leads to transcriptional
      induction of Notch function, which in turn limits HGF activity through repression
      of the Met oncogene.

PMID- 15870273
TI  - MyoD targets chromatin remodeling complexes to the myogenin locus prior to
      forming a stable DNA-bound complex.
AB  - The activation of muscle-specific gene expression requires the coordinated action
      of muscle regulatory proteins and chromatin-remodeling enzymes. Microarray
      analysis performed in the presence or absence of a dominant-negative BRG1 ATPase
      demonstrated that approximately one-third of MyoD-induced genes were highly
      dependent on SWI/SNF enzymes. To understand the mechanism of activation, we
      performed chromatin immunoprecipitations analyzing the myogenin promoter. We
      found that H4 hyperacetylation preceded Brg1 binding in a MyoD-dependent manner
      but that MyoD binding occurred subsequent to H4 modification and Brg1
      interaction. In the absence of functional SWI/SNF enzymes, muscle regulatory
      proteins did not bind to the myogenin promoter, thereby providing evidence for
      SWI/SNF-dependent activator binding. We observed that the homeodomain factor
      Pbx1, which cooperates with MyoD to stimulate myogenin expression, is
      constitutively bound to the myogenin promoter in a SWI/SNF-independent manner,
      suggesting a two-step mechanism in which MyoD initially interacts indirectly with
      the myogenin promoter and attracts chromatin-remodeling enzymes, which then
      facilitate direct binding by MyoD and other regulatory proteins.

PMID- 15870274
TI  - The LIM protein Ajuba influences interleukin-1-induced NF-kappaB activation by
      affecting the assembly and activity of the protein kinase Czeta/p62/TRAF6
      signaling complex.
AB  - The Zyxin/Ajuba family of cytosolic LIM domain-containing proteins has the
      potential to shuttle from sites of cell adhesion into the nucleus and thus can be
      candidate transducers of environmental signals. To understand Ajuba's role in
      signal transduction pathways, we performed a yeast two-hybrid screen with the LIM
      domain region of Ajuba. We identified the atypical protein kinase C (aPKC)
      scaffold protein p62 as an Ajuba binding partner. A prominent function of p62 is
      the regulation of NF-kappaB activation in response to interleukin-1 (IL-1) and
      tumor necrosis factor signaling through the formation of an aPKC/p62/TRAF6
      multiprotein signaling complex. In addition to p62, we found that Ajuba also
      interacted with tumor necrosis factor receptor-associated factor 6 (TRAF6) and
      PKCzeta. Ajuba recruits TRAF6 to p62 and in vitro activates PKCzeta activity and
      is a substrate of PKCzeta. Ajuba null mouse embryonic fibroblasts (MEFs) and
      lungs were defective in NF-kappaB activation following IL-1 stimulation, and in
      lung IKK activity was inhibited. Overexpression of Ajuba in primary MEFs enhances
      NF-kappaB activity following IL-1 stimulation. We propose that Ajuba is a new
      cytosolic component of the IL-1 signaling pathway modulating IL-1-induced NF
      kappaB activation by influencing the assembly and activity of the aPKC/p62/TRAF6
      multiprotein signaling complex.

PMID- 15870275
TI  - Human hHpr1/p84/Thoc1 regulates transcriptional elongation and physically links
      RNA polymerase II and RNA processing factors.
AB  - Cotranscriptional loading of RNA processing factors onto nascent RNA facilitates
      efficient gene expression. Mechanisms responsible for coupling transcription and
      RNA processing are not well defined, but the Saccharomyces cerevisiae TREX
      complex provides an example. TREX is composed of the subcomplex THO that
      associates with RNA polymerase II and is required for normal transcriptional
      elongation. THO associates with proteins involved in RNA splicing and export to
      form the larger TREX complex. Hence, assembly of TREX physically couples
      transcriptional elongation with RNA processing factors. Whether metazoan species
      with long, intron-containing genes utilize a similar mechanism has not been
      established. Here we show that human hHpr1/p84/Thoc1 associates with elongating
      RNA polymerase II and the RNA splicing and export factor UAP56 in intact cells.
      Depletion of hHpr1/p84/Thoc1 causes transcriptional elongation defects and
      associated cellular phenotypes similar to those observed in THO-deficient yeast.
      We conclude that hHpr1/p84/Thoc1 regulates transcriptional elongation and may
      participate in a protein complex functionally analogous to yeast TREX, physically
      linking elongating RNA polymerase II with RNA processing factors.

PMID- 15870276
TI  - Restoration of functional gap junctions through internal ribosome entry site
      dependent synthesis of endogenous connexins in density-inhibited cancer cells.
AB  - Gap junctions are composed of connexins and are critical for the maintenance of
      the differentiated state. Consistently, connexin expression is impaired in most
      cancer cells, and forced expression of connexins following cDNA transfection
      reverses the tumor phenotype. We have found that the restoration of density
      inhibition of human pancreatic cancer cells by the antiproliferative somatostatin
      receptor 2 (sst2) is due to overexpression of endogenous connexins Cx26 and Cx43
      and consequent formation of functional gap junctions. Immunoblotting along with
      protein metabolic labeling and mRNA monitoring revealed that connexin expression
      is enhanced at the level of translation but is not sensitive to the inhibition of
      cap-dependent translation initiation. Furthermore, we identified a new internal
      ribosome entry site (IRES) in the Cx26 mRNA. The activity of Cx26 IRES and that
      of the previously described Cx43 IRES are enhanced in density-inhibited cells.
      These data indicate that the restoration of functional gap junctions is likely a
      critical event in the antiproliferative action of the sst2 receptor. We further
      suggest that the existence of IRESes in connexin mRNAs permits connexin
      expression in density-inhibited or differentiated cells, where cap-dependent
      translation is generally reduced.

PMID- 15870277
TI  - Transcriptional control of BubR1 by p53 and suppression of centrosome
      amplification by BubR1.
AB  - Elimination of the regulatory mechanism underlying numeral homeostasis of
      centrosomes, as seen in cells lacking p53, results in abnormal amplification of
      centrosomes, which increases the frequency of chromosome segregation errors, and
      thus contributes to the chromosome instability frequently observed in cancer
      cells. We have previously reported that p53(-/-) mouse cells in prolonged culture
      undergo genomic convergence similar to that observed during tumor progression;
      early-passage p53(-/-) cells are karyotypically heterogeneous due to extensive
      chromosome instability associated with centrosome amplification, while late
      passage p53(-/-) cells are aneuploid yet karyotypically homogeneous and
      chromosomally stable. Moreover, they contain numerically normal centrosomes.
      Through the microarray analysis of early- and late-passage p53(-/-) cells, we
      identified the BubR1 spindle checkpoint protein, which plays a critical role in
      suppression of centrosome amplification and stabilization of chromosomes in late
      passage p53(-/-) cells. Up-regulation of BubR1 augments the checkpoint function,
      which effectively senses the spindle/chromosome aberrations associated with
      centrosome amplification. We further found that BubR1 transcription is largely
      controlled by p53. In early-passage p53(-/-) cells, BubR1 expression is low and
      the checkpoint function in response to microtubule toxin is considerably
      compromised. In late-passage cells, however, regaining of BubR1 expression
      restores the checkpoint function to mitotic aberrations caused by microtubule
      toxin. Our studies demonstrate the molecular aspect of genomic convergence in
      cultured cells, providing critical information for understanding the stepwise
      progression of tumors.

PMID- 15870278
TI  - Silencing mitosin induces misaligned chromosomes, premature chromosome
      decondensation before anaphase onset, and mitotic cell death.
AB  - Mitosin (also named CENP-F) is a large human nuclear protein transiently
      associated with the outer kinetochore plate in M phase. Using RNA interference
      and fluorescence microscopy, we showed that mitosin depletion attenuated
      chromosome congression and led to metaphase arrest with misaligned polar
      chromosomes whose kinetochores showed few cold-stable microtubules. Kinetochores
      of fully aligned chromosomes often failed to show orientation in the direction of
      the spindle long axis. Moreover, tension across their sister kinetochores was
      decreased by 53% on average. These phenotypes collectively imply defects in motor
      functions in mitosin-depleted cells and are similar to those of CENP-E depletion.
      Consistently, the intensities of CENP-E and cytoplasmic dynein and dynactin,
      which are motors controlling microtubule attachment and chromosome movement, were
      reduced at the kinetochore in a microtubule-dependent manner. In addition, after
      being arrested in pseudometaphase for approximately 2 h, mitosin-depleted cells
      died before anaphase initiation through apoptosis. The dying cells exhibited
      progressive chromosome arm decondensation, while the centromeres were still
      associated with spindles. Mitosin is therefore essential for full chromosome
      alignment, possibly by promoting proper kinetochore attachments through
      modulating CENP-E and dynein functions. Its depletion also prematurely triggers
      chromosome decondensation, a process that normally occurs from telophase for the
      nucleus reassembly, thus resulting in apoptosis.

PMID- 15870279
TI  - Dynamical remodeling of the transcriptome during short-term anaerobiosis in
      Saccharomyces cerevisiae: differential response and role of Msn2 and/or Msn4 and
      other factors in galactose and glucose media.
AB  - In contrast to previous steady-state analyses of the O(2)-responsive
      transcriptome, here we examined the dynamics of the response to short-term
      anaerobiosis (2 generations) in both catabolite-repressed (glucose) and
      derepressed (galactose) cells, assessed the specific role that Msn2 and Msn4 play
      in mediating the response, and identified gene networks using a novel clustering
      approach. Upon shifting cells to anaerobic conditions in galactose medium, there
      was an acute ( approximately 10 min) yet transient (<45 min) induction of Msn2-
      and/or Msn4-regulated genes associated with the remodeling of reserve energy and
      catabolic pathways during the switch from mixed respiro-fermentative to strictly
      fermentative growth. Concomitantly, MCB- and SCB-regulated networks associated
      with the G(1)/S transition of the cell cycle were transiently down-regulated
      along with rRNA processing genes containing PAC and RRPE motifs. Remarkably, none
      of these gene networks were differentially expressed when cells were shifted in
      glucose, suggesting that a metabolically derived signal arising from the abrupt
      cessation of respiration, rather than O(2) deprivation per se, elicits this
      "stress response." By approximately 0.2 generation of anaerobiosis in both media,
      more chronic, heme-dependent effects were observed, including the down-regulation
      of Hap1-regulated networks, derepression of Rox1-regulated networks, and
      activation of Upc2-regulated ones. Changes in these networks result in the
      functional remodeling of the cell wall, sterol and sphingolipid metabolism, and
      dissimilatory pathways required for long-term anaerobiosis. Overall, this study
      reveals that the acute withdrawal of oxygen can invoke a metabolic state
      dependent "stress response" but that acclimatization to oxygen deprivation is a
      relatively slow process involving complex changes primarily in heme-regulated
      gene networks.

PMID- 15870280
TI  - The nuclear import of TAF10 is regulated by one of its three histone fold domain
      containing interaction partners.
AB  - TFIID, comprising the TATA box binding protein (TBP) and 13 TBP-associated
      factors (TAFs), plays a role in nucleation in the assembly of the RNA polymerase
      II preinitiation complexes on protein-encoding genes. TAFs are shared among other
      transcription regulatory complexes (e.g., SAGA, TBP-free TAF-containing complex
      [TFTC], STAGA, and PCAF/GCN5). Human TAF10, a subunit of both TFIID and TFTC, has
      three histone fold-containing interaction partners: TAF3, TAF8, and SPT7Like
      (SPT7L). In human cells, exogenously expressed TAF10 remains rather cytoplasmic
      and leptomycin B does not affect this localization. By using fluorescent fusion
      proteins, we show that TAF10 does not have an intrinsic nuclear localization
      signal (NLS) and needs one of its three interaction partners to be transported
      into the nucleus. When the NLS sequences of either TAF8 or SPT7L are mutated,
      TAF10 remains cytoplasmic, but a heterologous NLS can drive TAF10 into the
      nucleus. Experiments using fluorescence recovery after photobleaching show that
      TAF10 does not associate with any cytoplasmic partner but that once transported
      into the nucleus it binds to nuclear structures. TAF10 binding to importin beta
      in vitro is dependent on the coexpression of either TAF8 or TAF3, but not SPT7L.
      The cytoplasmic-nuclear transport of TAF10 is naturally observed during the
      differentiation of adult male germ cells. Thus, here we describe a novel role of
      the three mammalian interacting partners in the nuclear localization of TAF10,
      and our data suggest that a complex network of regulated cytoplasmic associations
      may exist among these factors and that this network is important for the
      composition of different TFIID and TFTC-type complexes in the nucleus.

PMID- 15870281
TI  - The docking protein FRS2alpha is an essential component of multiple fibroblast
      growth factor responses during early mouse development.
AB  - The docking protein FRS2alpha is a major mediator of fibroblast growth factor
      (FGF) signaling. However, the physiological role of FRS2alpha in vivo remains
      unknown. In this report, we show that Frs2alpha-null mouse embryos have a defect
      in anterior-posterior (A-P) axis formation and are developmentally retarded,
      resulting in embryonic lethality by embryonic day 8. We demonstrate that
      FRS2alpha is essential for the maintenance of self-renewing trophoblast stem (TS)
      cells in response to FGF4 in the extraembryonic ectoderm (ExE) that gives rise to
      tissues of the placenta. By analyzing chimeric embryos, we found that FRS2alpha
      also plays a role in cell movement through the primitive streak during
      gastrulation. In addition, experiments are presented demonstrating that Bmp4
      expression in TS cells is controlled by mitogen-activated protein kinase
      dependent FGF4 stimulation. Moreover, both the expression of Bmp4 in ExE and
      activation of Smad1/5 in epiblasts are reduced in Frs2alpha-null embryos. These
      experiments underscore the critical role of FRS2alpha in mediating multiple
      processes during embryonic development and reveal a potential new link between
      FGF and Bmp4 signaling pathways in early embryogenesis.

PMID- 15870282
TI  - Regulation of the small GTPase Rap1 and extracellular signal-regulated kinases by
      the costimulatory molecule CTLA-4.
AB  - The mitogen-activated protein kinase extracellular signal-regulated kinase (ERK)
      is activated following engagement of the T-cell receptor and is required for
      interleukin 2 (IL-2) production and T-cell proliferation. This activation is
      enhanced by stimulation of the coreceptor CD28 and inhibited by the coreceptor
      CTLA-4. We show that the small G protein Rap1 is regulated in the opposite
      manner; it is inhibited by CD28 and activated by CTLA-4. Together, CD3 and CTLA-4
      activate Rap1 in a sustained manner. To delineate T-cell function in the absence
      of Rap1 activity, we generated transgenic mice expressing Rap1GAP1, a Rap1
      specific GTPase-activating protein. Transgenic mice showed lymphadenopathy, and
      transgenic T cells displayed increased ERK activation, proliferation, and IL-2
      production. More significantly, the inhibitory effect of CTLA-4 on T-cell
      function in Rap1GAP1-transgenic T cells was reduced. We demonstrate that CTLA-4
      activates Rap1, and we propose that intracellular signals from CTLA-4 antagonize
      CD28, at least in part, at the level of Rap1.

PMID- 15870283
TI  - The ciliary rootlet maintains long-term stability of sensory cilia.
AB  - The striated ciliary rootlet is a prominent cytoskeleton originating from basal
      bodies of ciliated cells. Although a familiar structure in cell biology, its
      function has remained unresolved. In this study, we carried out targeted
      disruption in mice of the gene for rootletin, a component of the rootlet. In the
      mutant, ciliated cells are devoid of rootlets. Phototransduction and ciliary
      beating in sensory and motile cilia initially exhibit no apparent functional
      deficits. However, photoreceptors degenerate over time, and mutant lungs appear
      prone to pathological changes consistent with insufficient mucociliary clearance.
      Further analyses revealed a striking fragility at the ciliary base in
      photoreceptors lacking rootlets. In vitro assays suggest that the rootlet is
      among the least dynamic of all cytoskeletons and interacts with actin filaments.
      Thus, a primary function of the rootlet is to provide structural support for the
      cilium. Inasmuch as photoreceptors elaborate an exceptionally enlarged sensory
      cilium, they are especially dependent on the rootlet for structural integrity and
      long-term survival.

PMID- 15870284
TI  - ABCA5 resides in lysosomes, and ABCA5 knockout mice develop lysosomal disease
      like symptoms.
AB  - ABCA5 is a member of the ABC transporter A subfamily, and a mouse orthologue
      (mABCA5) in newborn mouse brain and neural cells was identified by reverse
      transcription-PCR. Full-length cDNA cloning revealed that mABCA5 consists of
      1,642 amino acid residues and that its putative structure is that of a full-type
      ABC transporter having two sets of six transmembrane segments and a nucleotide
      binding domain. Immunohistochemical studies revealed that mABCA5 is expressed in
      brain, lung, heart, and thyroid gland. A subcellular localization analysis showed
      that mABCA5 is a resident of lysosomes and late endosomes. Abca5(-)(/)(-) mice
      exhibited symptoms similar to those of several lysosomal diseases in heart,
      although no prominent abnormalities were found in brain or lung. They developed a
      dilated cardiomyopathy-like heart after reaching adulthood and died due to
      depression of the cardiovascular system. In addition, Abca5(-)(/)(-) mice also
      exhibited exophthalmos and collapse of the thyroid gland. Therefore, ABCA5 is a
      protein related to a lysosomal disease and plays important roles, especially in
      cardiomyocytes and follicular cells.

PMID- 15870285
TI  - Glucocorticoid receptor (GR)-associated SMRT binding to C/EBPbeta TAD and Nrf2
      Neh4/5: role of SMRT recruited to GR in GSTA2 gene repression.
AB  - The expression of the glutathione S-transferase gene (GST), whose induction
      accounts for cancer chemoprevention, is regulated by activation of CCAAT/enhancer
      binding protein beta (C/EBPbeta) and NF-E2-related factor 2 (Nrf2). The present
      study investigated the repressing effects of activating glucocorticoid receptor
      (GR) on C/EBPbeta- and Nrf2-mediated GSTA2 gene induction and the mechanism.
      Dexamethasone that activates GR inhibited constitutive and oltipraz- or tert
      butylhydroquinone (t-BHQ)-inducible GSTA2 expression in H4IIE cells. Also,
      dexamethasone repressed GSTA2 promoter-luciferase gene activity. Dexamethasone-GR
      activation did not inhibit nuclear translocation of C/EBPbeta or Nrf2 nor their
      DNA binding activities induced by oltipraz or t-BHQ. Deletion of the
      glucocorticoid response element (GRE) in the GSTA2 promoter abolished
      dexamethasone inhibition of the gene induction. Immunoprecipitation
      immunoblotting, chromatin immunoprecipitation, and GST pull-down assays revealed
      that silencing mediator for retinoid and thyroid hormone receptors (SMRT), a
      corepressor recruited to steroid-GR complex for histone deacetylation, bound to
      TAD domain of C/EBPbeta and Neh4/5 domain of Nrf2. The GSTA2 promoter-luciferase
      activities were decreased by SMRT but not by truncated SMRTs. The small
      interference RNA (siRNA) against SMRT abolished SMRT repression of the gene
      induction by C/EBPbeta or Nrf2. The plasmid transfection and siRNA experiments
      directly evidenced the functional role of SMRT in GSTA2 repression. In
      conclusion, dexamethasone antagonizes C/EBPbeta- and Nrf2-mediated GSTA2 gene
      induction via ligand-GR binding to the GRE, and steroid-mediated GSTA2 repression
      involves inactivation of C/EBPbeta and Nrf2 by SMRT recruited to steroid-GR
      complex.

PMID- 15870286
TI  - Neuronal leucine-rich repeat protein 4 functions in hippocampus-dependent long
      lasting memory.
AB  - Neuronal leucine-rich repeat proteins (NLRRs) are type I transmembrane proteins
      and expressed in neuronal tissues, but their function remains unknown. Here, we
      describe the identification and characterization of a new member of the NLRR
      family, NLRR4, and its potential role in long-lasting memory. We generated NLRR4
      deficient (NLRR4(-/-)) mice and found that they showed impaired memory retention.
      In hippocampus-dependent learning tasks, NLRR4(-/-) mice were able to learn and
      maintain the memories for one day but unable to retain the memories for four days
      after learning. In contrast, in a hippocampus-independent task, NLRR4(-/-) mice
      were able to retain the memory normally for at least seven days. These results
      suggest that NLRR4 plays a key role in hippocampus-dependent long-lasting memory.

PMID- 15870287
TI  - Role of epidermal growth factor receptor signaling in RAS-driven melanoma.
AB  - The identification of essential genetic elements in pathways governing the
      maintenance of fully established tumors is critical to the development of
      effective antioncologic agents. Previous studies revealed an essential role for H
      RAS(V12G) in melanoma maintenance in an inducible transgenic model. Here, we
      sought to define the molecular basis for RAS-dependent tumor maintenance through
      determination of the H-RAS(V12G)-directed transcriptional program and subsequent
      functional validation of potential signaling surrogates. The extinction of H
      RAS(V12G) expression in established tumors was associated with alterations in the
      expression of proliferative, antiapoptotic, and angiogenic genes, a profile
      consistent with the observed phenotype of tumor cell proliferative arrest and
      death and endothelial cell apoptosis during tumor regression. In particular,
      these melanomas displayed a prominent RAS-dependent regulation of the epidermal
      growth factor (EGF) family, leading to establishment of an EGF receptor signaling
      loop. Genetic complementation and interference studies demonstrated that this
      signaling loop is essential to H-RAS(V12G)-directed tumorigenesis. Thus, this
      inducible tumor model system permits the identification and validation of
      alternative points of therapeutic intervention without neutralization of the
      primary genetic lesion.

PMID- 15870288
TI  - Energy homeostasis and gastrointestinal endocrine differentiation do not require
      the anorectic hormone peptide YY.
AB  - The gastrointestinal hormone peptide YY is a potent inhibitor of food intake and
      is expressed early during differentiation of intestinal and pancreatic endocrine
      cells. In order to better understand the role of peptide YY in energy homeostasis
      and development, we created mice with a targeted deletion of the peptide YY gene.
      All intestinal and pancreatic endocrine cells developed normally in the absence
      of peptide YY with the exception of pancreatic polypeptide (PP) cells, indicating
      that peptide YY expression was not required for terminal differentiation. We used
      recombination-based cell lineage trace to determine if peptide YY cells were
      progenitors for gastrointestinal endocrine cells. Peptide YY(+) cells gave rise
      to all L-type enteroendocrine cells and to islet partial differential and PP
      cells. In the pancreas, approximately 40% of pancreatic alpha and rare beta cells
      arose from peptide YY(+) cells, suggesting that most beta cells and surprisingly
      the majority of alpha cells are not descendants of peptide YY(+)/glucagon
      positive/insulin-positive cells that appear during early pancreagenesis. Despite
      the anorectic effects of exogenous peptide YY(3-36) following intraperitoneal
      administration, mice lacking peptide YY showed normal growth, food intake, energy
      expenditure, and responsiveness to peptide YY(3-36). These observations suggest
      that targeted disruption of the peptide YY gene does not perturb terminal
      endocrine cell differentiation or the control of food intake and energy
      homeostasis.

PMID- 15870289
TI  - Expression, regulation, and requirement of the toll transmembrane protein during
      dorsal vessel formation in Drosophila melanogaster.
AB  - Early heart development in Drosophila and vertebrates involves the specification
      of cardiac precursor cells within paired progenitor fields, followed by their
      movement into a linear heart tube structure. The latter process requires
      coordinated cell interactions, migration, and differentiation as the primitive
      heart develops toward status as a functional organ. In the Drosophila embryo,
      cardioblasts emerge from bilateral dorsal mesoderm primordia, followed by
      alignment as rows of cells that meet at the midline and morph into a dorsal
      vessel. Genes that function in coordinating cardioblast organization, migration,
      and assembly are integral to heart development, and their encoded proteins need
      to be understood as to their roles in this vital morphogenetic process. Here we
      prove the Toll transmembrane protein is expressed in a secondary phase of heart
      formation, at lateral cardioblast surfaces as they align, migrate to the midline,
      and form the linear tube. The Toll dorsal vessel enhancer has been characterized,
      with its activity controlled by Dorsocross and Tinman transcription factors.
      Consistent with the observed protein expression pattern, phenotype analyses
      demonstrate Toll function is essential for normal dorsal vessel formation. Such
      findings implicate Toll as a critical cell adhesion molecule in the alignment and
      migration of cardioblasts during dorsal vessel morphogenesis.

PMID- 15870291
TI  - Generation and characterization of Rgs4 mutant mice.
AB  - RGS proteins are negative regulators of signaling through heterotrimeric G
      protein-coupled receptors and, as such, are in a position to regulate a plethora
      of biological phenomena. However, those have just begun to be explored in vivo.
      Here, we describe a mouse line deficient for Rgs4, a gene normally expressed
      early on in discrete populations of differentiating neurons and later on at
      multiple sites of the central nervous system, the cortex in particular, where it
      is one of the most highly transcribed Rgs genes. Rgs4(lacZ/lacZ) mice had normal
      neural development and were viable and fertile. Behavioral testing on mutant
      adults revealed subtle sensorimotor deficits but, so far, supported neither the
      proposed status of Rgs4 as a schizophrenia susceptibility gene (by showing intact
      prepulse inhibition in the mutants) nor (unlike another member of the Rgs family,
      Rgs9) a role of Rgs4 in the acute or chronic response to opioids.

PMID- 15870290
TI  - Vav activation and function as a rac guanine nucleotide exchange factor in
      macrophage colony-stimulating factor-induced macrophage chemotaxis.
AB  - Signal transduction mediated by phosphatidylinositol 3-kinase (PI 3-kinase) is
      regulated by hydrolysis of its products, a function performed by the 145-kDa SH2
      domain-containing inositol phosphatase (SHIP). Here, we show that bone marrow
      macrophages of SHIP(-/-) animals have elevated levels of phosphatidylinositol
      3,4,5-trisphosphate [PI (3,4,5)P(3)] and displayed higher and more prolonged
      chemotactic responses to macrophage colony-stimulating factor (M-CSF) and
      elevated levels of F-actin relative to wild-type macrophages. We also found that
      the small GTPase Rac was constitutively active and its upstream activator Vav was
      constitutively phosphorylated in SHIP(-/-) macrophages. Furthermore, we show that
      Vav in wild-type macrophages is recruited to the membrane in a PI 3-kinase
      dependent manner through the Vav pleckstrin homology domain upon M-CSF
      stimulation. Dominant inhibitory mutants of both Rac and Vav blocked chemotaxis.
      We conclude that Vav acts as a PI 3-kinase-dependent activator for Rac activation
      in macrophages stimulated with M-CSF and that SHIP regulates macrophage M-CSF
      triggered chemotaxis by hydrolysis of PI (3,4,5)P(3).

PMID- 15870292
TI  - Targeted disruption of the Mn1 oncogene results in severe defects in development
      of membranous bones of the cranial skeleton.
AB  - Fusion of the MN1 gene to TEL (ETV6) results in myeloid leukemia. The fusion
      protein combines the transcription activating domain of MN1 and the DNA binding
      domain of TEL and is thought to act as a deranged transcription factor. In
      addition, disruption of the large first exon of the MN1 gene is thought to
      inactivate MN1 function in a meningioma. To further investigate the role of MN1
      in cancer, we generated Mn1 knockout mice. Mn1(+/-) animals were followed for 30
      months, but they had no higher incidence of tumor formation than wild-type
      littermates. Mn1 null mice, however, were found to die at birth or shortly
      thereafter as the result of a cleft palate. Investigation of newborn or embryonic
      day 15.5 (E15.5) to E17.5 null mice revealed that the development of several
      bones in the skull was abnormal. The affected bones are almost exclusively formed
      by intramembranous ossification. They are either completely agenic at birth
      (alisphenoid and squamosal bones and vomer), hypoplastic, deformed (basisphenoid,
      pterygoid, and presphenoid), or substantially thinner (frontal, parietal, and
      interparietal bones). In heterozygous mice hypoplastic membranous bones and
      incomplete penetrance of the cleft palate were observed. We conclude that Mn1 is
      an important factor in development of membranous bones.

PMID- 15870293
TI  - The S1P2 receptor negatively regulates platelet-derived growth factor-induced
      motility and proliferation.
AB  - Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is the ligand
      for five specific G protein-coupled receptors, named S1P(1) to S1P(5). In this
      study, we found that cross-communication between platelet-derived growth factor
      receptor and S1P(2) serves as a negative damper of PDGF functions. Deletion of
      the S1P(2) receptor dramatically increased migration of mouse embryonic
      fibroblasts toward S1P, serum, and PDGF but not fibronectin. This enhanced
      migration was dependent on expression of S1P(1) and sphingosine kinase 1 (SphK1),
      the enzyme that produces S1P, as revealed by downregulation of their expression
      with antisense RNA and small interfering RNA, respectively. Although S1P(2)
      deletion had no significant effect on tyrosine phosphorylation of the PDGF
      receptors or activation of extracellular signal-regulated kinase 1/2 or Akt
      induced by PDGF, it reduced sustained PDGF-dependent p38 phosphorylation and
      markedly enhanced Rac activation. Surprisingly, S1P(2)-null cells not only
      exhibited enhanced proliferation but also markedly increased SphK1 expression and
      activity. Conversely, reintroduction of S1P(2) reduced DNA synthesis and
      expression of SphK1. Thus, S1P(2) serves as a negative regulator of PDGF-induced
      migration and proliferation as well as SphK1 expression. Our results suggest that
      a complex interplay between PDGFR and S1P receptors determines their functions.

PMID- 15870294
TI  - Identification and characterization of SSTK, a serine/threonine protein kinase
      essential for male fertility.
AB  - Here we describe and characterize a small serine/threonine kinase (SSTK) which
      consists solely of the N- and C-lobes of a protein kinase catalytic domain. SSTK
      protein is highly conserved among mammals, and no close homologues were found in
      the genomes of nonmammalian organisms. SSTK specifically interacts with HSP90
      1beta, HSC70, and HSP70 proteins, and this association appears to be required for
      SSTK kinase activity. The SSTK transcript was most abundant in human and mouse
      testes but was also detected in all human tissues tested. In the mouse testis,
      SSTK protein was localized to the heads of elongating spermatids. Targeted
      deletion of the SSTK gene in mice resulted in male sterility due to profound
      impairment in motility and morphology of spermatozoa. A defect in DNA
      condensation in SSTK null mutants occurred in elongating spermatids at a step in
      spermiogenesis coincident with chromatin displacement of histones by transition
      proteins. SSTK phosphorylated histones H1, H2A, H2AX, and H3 but not H2B or H4 or
      transition protein 1 in vitro. These results demonstrate that SSTK is required
      for proper postmeiotic chromatin remodeling and male fertility. Abnormal sperm
      chromatin condensation is common in sterile men, and our results may provide
      insight into the molecular mechanisms underlying certain human infertility
      disorders.

PMID- 15870295
TI  - Hes1 directly controls cell proliferation through the transcriptional repression
      of p27Kip1.
AB  - A transcriptional regulator, Hes1, plays crucial roles in the control of
      differentiation and proliferation of neuronal, endocrine, and T-lymphocyte
      progenitors during development. Mechanisms for the regulation of cell
      proliferation by Hes1, however, remain to be verified. In embryonic carcinoma
      cells, endogenous Hes1 expression was repressed by retinoic acid in concord with
      enhanced p27(Kip1) expression and cell cycle arrest. Conversely, conditional
      expression of a moderate but not maximal level of Hes1 in HeLa cells by a
      tetracycline-inducible system resulted in reduced p27(Kip1) expression, which was
      attributed to decreased basal transcript rather than enhanced proteasomal
      degradation, with concomitant increases in the growth rate and saturation
      density. Hes1 induction repressed the promoter activity of a 5' flanking basal
      enhancer region of p27(Kip1) gene in a manner dependent on Hes1 expression
      levels, and this was mediated by its binding to class C sites in the promoter
      region. Finally, hypoplastic fetal thymi, as well as livers and brains of Hes1
      deficient mice, showed significantly increased p27(Kip1) transcripts compared
      with those of control littermates. These results have suggested that Hes1
      directly contributes to the promotion of progenitor cell proliferation through
      transcriptional repression of a cyclin-dependent kinase inhibitor, p27(Kip1).

PMID- 15870296
TI  - A small conserved surface in SUMO is the critical structural determinant of its
      transcriptional inhibitory properties.
AB  - Small ubiquitin-like modifier (SUMO) modification of sequence-specific
      transcription factors has profound regulatory consequences. By providing an
      intrinsic inhibitory function, SUMO isoforms can suppress transcriptional
      activation, particularly at promoters harboring multiple response elements.
      Through a comprehensive structure-function analysis, we have identified a single
      critical sector along the second beta sheet and the following alpha helix of
      SUMO2. This distinct surface is defined by four basic residues (K33, K35, K42,
      R50) that surround a shallow pocket lined by aliphatic (V30, I34) and polar (T38)
      residues. Substitutions within this area specifically and dramatically affected
      the ability of both SUMO2 and SUMO1 to inhibit transcription and revealed that
      the positively charged nature of the key basic residues is the main feature
      responsible for their functional role. This highly conserved surface accounts for
      the inhibitory properties of SUMO on multiple transcription factors and promoter
      contexts and likely defines the interaction surface for the corepressors that
      mediate the inhibitory properties of SUMO.

PMID- 15870297
TI  - A novel role for the mitotic spindle during DNA segregation in yeast: promoting 2
      microm plasmid-cohesin association.
AB  - The 2 microm circle plasmid in Saccharomyces cerevisiae is a model for a stable,
      high-copy-number, extrachromosomal "selfish" DNA element. By combining a
      partitioning system and an amplification system, the plasmid ensures its stable
      propagation and copy number maintenance, even though it does not provide any
      selective advantage to its host. Recent evidence suggests that the partitioning
      system couples plasmid segregation to chromosome segregation. We now demonstrate
      an unexpected and unconventional role for the mitotic spindle in the plasmid
      partitioning pathway. The spindle specifies the nuclear address of the 2 microm
      circle and promotes recruitment of the cohesin complex to the plasmid
      partitioning locus STB. Only the nuclear microtubules, and not the cytoplasmic
      ones, are required for loading cohesin at STB. In cells recovering from
      nocodazole-induced spindle depolymerization and G(2)/M arrest, cohesin-STB
      association can be established coincident with spindle restoration. This
      postreplication recruitment of cohesin is not functional in equipartitioning.
      However, normally acquired cohesin can be inactivated after replication without
      causing plasmid missegregation. In the mtw1-1 mutant yeast strain, the plasmid
      cosegregates with the spindle and the spindle-associated chromosomes; by
      contrast, a substantial number of the chromosomes are not associated with the
      spindle. These results are consistent with a model in which the spindle promotes
      plasmid segregation in a chromosome-linked fashion.

PMID- 15870298
TI  - The 2 microm plasmid causes cell death in Saccharomyces cerevisiae with a
      mutation in Ulp1 protease.
AB  - The 2 microm circle plasmid confers no phenotype in wild-type Saccharomyces
      cerevisiae but in a nib1 mutant, an elevated plasmid copy number is associated
      with cell death. Complementation was used to identify nib1 as a mutant allele of
      the ULP1 gene that encodes a protease required for removal of a ubiquitin-like
      protein, Smt3/SUMO, from protein substrates. The nib1 mutation replaces conserved
      tryptophan 490 with leucine in the protease domain of Ulp1. Complete deletion of
      ULP1 is lethal, even in a strain that lacks the 2 microm circle. Partial deletion
      of ULP1, like the nib1 mutation, results in clonal variations in plasmid copy
      number. In addition, a subset of these mutant cells produces lineages in which
      all cells have reduced proliferative capacity, and this phenotype is dependent
      upon the presence of the 2 microm circle. Segregation of the 2 microm circle
      requires two plasmid-encoded proteins, Rep1 and Rep2, which were found to
      colocalize with Ulp1 protein in the nucleus and interact with Smt3 in a two
      hybrid assay. These associations and the observation of missegregation of a
      fluorescently tagged 2 microm circle reporter plasmid in a subset of ulp1 mutant
      cells suggest that Smt3 modification plays a role in both plasmid copy number
      control and segregation.

PMID- 15870299
TI  - Misregulation of 2 microm circle copy number in a SUMO pathway mutant.
AB  - Attachment of the ubiquitin-like protein SUMO to other proteins is an essential
      process in Saccharomyces cerevisiae. However, yeast mutants lacking the SUMO
      ligases Siz1 and Siz2/Nfi1 are viable, even though they show dramatically reduced
      levels of SUMO conjugation. This siz1Delta siz2Delta double mutant is cold
      sensitive and has an unusual phenotype in that it forms irregularly shaped
      colonies that contain sectors of wild-type-appearing cells as well as sectors of
      enlarged cells that are arrested in G(2)/M. We have found that these phenotypes
      result from misregulation of the copy number of the endogenous yeast plasmid, the
      2 microm circle. siz1Delta siz2Delta mutants have up to 40-fold-higher levels of
      2 microm than do wild-type strains. Furthermore, 2 microm is responsible for the
      siz1Delta siz2Delta mutant's obvious growth defects, as siz1Delta siz2Delta
      [cir(0)] strains, which lack 2 microm, are no longer heterogeneous and show
      growth characteristics similar to those of the wild type. Possible mechanisms for
      SUMO's effect on 2 microm are suggested by the finding that both Flp1 recombinase
      and Rep2, two of the four proteins encoded by 2 microm, are covalently modified
      by SUMO. Our data suggest that SUMO attachment negatively regulates Flp1 levels,
      which may partially account for the increased 2 microm copy number in the
      siz1Delta siz2Delta strain.

PMID- 15870301
TI  - Toward a system of microbial forensics: from sample collection to interpretation
      of evidence.

PMID- 15870300
TI  - TAF1 histone acetyltransferase activity in Sp1 activation of the cyclin D1
      promoter.
AB  - A missense mutation within the histone acetyltransferase (HAT) domain of the TATA
      binding protein-associated factor TAF1 induces ts13 cells to undergo a late G(1)
      arrest and decreases cyclin D1 transcription. We have found that TAF1 mutants
      (Delta844-850 and Delta848-850, from which amino acids 844 through 850 and 848
      through 850 have been deleted, respectively) deficient in HAT activity are unable
      to complement the ts13 defect in cell proliferation and cyclin D1 transcription.
      Chromatin immunoprecipitation assays revealed that histone H3 acetylation was
      reduced at the cyclin D1 promoter but not the c-fos promoter upon inactivation of
      TAF1 in ts13 cells. The hypoacetylation of H3 at the cyclin D1 promoter was
      reversed by treatment with trichostatin A (TSA), a histone deacetylase inhibitor,
      or by expression of TAF1 proteins that retain HAT activity. Transcription of a
      chimeric promoter containing the Sp1 sites of cyclin D1 and c-fos core remained
      TAF1 dependent in ts13 cells. Treatment with TSA restored full activity to the
      cyclin D1-c-fos chimera at 39.5 degrees C. In vivo genomic footprinting
      experiments indicate that protein-DNA interactions at the Sp1 sites of the cyclin
      D1 promoter were compromised at 39.5 degrees C in ts13 cells. These data have led
      us to hypothesize that TAF1-dependent histone acetylation facilitates
      transcription factor binding to the Sp1 sites, thereby activating cyclin D1
      transcription and ultimately G(1)-to-S-phase progression.

PMID- 15870302
TI  - Substrate specificity and colorimetric assay for recombinant TrzN derived from
      Arthrobacter aurescens TC1.
AB  - The TrzN protein, which is involved in s-triazine herbicide catabolism by
      Arthrobacter aurescens TC1, was cloned and expressed in Escherichia coli as a His
      tagged protein. The recombinant protein was purified via nickel column
      chromatography. The purified TrzN protein was tested with 31 s-triazine and
      pyrimidine ring compounds; 22 of the tested compounds were substrates. TrzN
      showed high activity with sulfur-substituted s-triazines and the highest activity
      with ametryn sulfoxide. Hydrolysis of ametryn sulfoxide by TrzN, both in vitro
      and in vivo, yielded a product(s) that reacted with 7-chloro-4-nitrobenz-2-oxa
      1,3-diazole (NBD-Cl) to generate a diagnostic blue product. Atrazine
      chlorohydrolase, AtzA, did not hydrolyze ametryn sulfoxide, and no color was
      formed by amending those enzyme incubations with NBD-Cl. TrzN and AtzA could also
      be distinguished by reaction with ametryn. TrzN, but not AtzA, hydrolyzed ametryn
      to methylmercaptan. Methylmercaptan reacted with NBD-Cl to produce a diagnostic
      yellow product having an absorption maximum at 420 nm. The yellow color with
      ametryn was shown to selectively demonstrate the presence of TrzN, but not AtzA
      or other enzymes, in whole microbial cells. The present study was the first to
      purify an active TrzN protein in recombinant form and develop a colorimetric test
      for determining TrzN activity, and it significantly extends the known substrate
      range for TrzN.

PMID- 15870303
TI  - Potential uptake of Escherichia coli O157:H7 from organic manure into crisphead
      lettuce.
AB  - To investigate the potential transfer of Escherichia coli O157:H7 from
      contaminated manure to fresh produce, lettuce seedlings were transplanted into
      soil fertilized with bovine manure which had been inoculated with approximately
      10(4) CFU g(-1) E. coli O157:H7. The lettuce was grown for approximately 50 days
      in beds in climate-controlled rooms in a greenhouse. As the bacterium was not
      detected in the edible parts of the lettuce, the outer leaves of the lettuce, or
      the lettuce roots at harvest it was concluded that transmission of E. coli
      O157:H7 from contaminated soil to lettuce did not occur. The pathogen persisted
      in the soil for at least 8 weeks after fertilizing but was not detected after 12
      weeks. Indigenous E. coli was detected only sporadically on the lettuce at
      harvest, and enterococci were not detected at all. The numbers of enterococci
      declined more rapidly than those of E. coli in the soil. Pseudomonas fluorescens,
      which inhibited growth of E. coli O157:H7 in vitro, was isolated from the
      rhizosphere.

PMID- 15870304
TI  - Induction of oxidative stress by high hydrostatic pressure in Escherichia coli.
AB  - Using leaderless alkaline phosphatase as a probe, it was demonstrated that
      pressure treatment induces endogenous intracellular oxidative stress in
      Escherichia coli MG1655. In stationary-phase cells, this oxidative stress
      increased with the applied pressure at least up to 400 MPa, which is well beyond
      the pressure at which the cells started to become inactivated (200 MPa). In
      exponential-phase cells, in contrast, oxidative stress increased with pressure
      treatment up to 150 MPa and then decreased again, together with the cell counts.
      Anaerobic incubation after pressure treatment significantly supported the
      recovery of MG1655, while mutants with increased intrinsic sensitivity toward
      oxidative stress (katE, katF, oxyR, sodAB, and soxS) were found to be more
      pressure sensitive than wild-type MG1655. Furthermore, mild pressure treatment
      strongly sensitized E. coli toward t-butylhydroperoxide and the superoxide
      generator plumbagin. Finally, previously described pressure-resistant mutants of
      E. coli MG1655 displayed enhanced resistance toward plumbagin. In one of these
      mutants, the induction of endogenous oxidative stress upon high hydrostatic
      pressure treatment was also investigated and found to be much lower than in
      MG1655. These results suggest that, at least under some conditions, the
      inactivation of E. coli by high hydrostatic pressure treatment is the consequence
      of a suicide mechanism involving the induction of an endogenous oxidative burst.

PMID- 15870305
TI  - Identification of unique type II polyketide synthase genes in soil.
AB  - Many bacteria, particularly actinomycetes, are known to produce secondary
      metabolites synthesized by polyketide synthases (PKS). Bacterial polyketides are
      a particularly rich source of bioactive molecules, many of which are of potential
      pharmaceutical relevance. To directly access PKS gene diversity from soil, we
      developed degenerate PCR primers for actinomycete type II KS(alpha)
      (ketosynthase) genes. Twenty-one soil samples were collected from diverse sources
      in New Jersey, and their bacterial communities were compared by terminal
      restriction fragment length polymorphism (TRFLP) analysis of PCR products
      generated using bacterial 16S rRNA gene primers (27F and 1525R) as well as an
      actinomycete-specific forward primer. The distribution of actinomycetes was
      highly variable but correlated with the overall bacterial species composition as
      determined by TRFLP. Two samples were identified to contain a particularly rich
      and unique actinomycete community based on their TRFLP patterns. The same samples
      also contained the greatest diversity of KS(alpha) genes as determined by TRFLP
      analysis of KS(alpha) PCR products. KS(alpha) PCR products from these and three
      additional samples with interesting TRFLP pattern were cloned, and seven novel
      clades of KS(alpha) genes were identified. Greatest sequence diversity was
      observed in a sample containing a moderate number of peaks in its KS(alpha)
      TRFLP. The nucleotide sequences were between 74 and 81% identical to known
      sequences in GenBank. One cluster of sequences was most similar to the KS(alpha)
      involved in ardacin (glycopeptide antibiotic) production by Kibdelosporangium
      aridum. The remaining sequences showed greatest similarity to the KS(alpha) genes
      in pathways producing the angucycline-derived antibiotics simocyclinone,
      pradimicin, and jasomycin.

PMID- 15870306
TI  - Relationship between pH and medium dissolved solids in terms of growth and
      metabolism of lactobacilli and Saccharomyces cerevisiae during ethanol
      production.
AB  - The specific growth rates of four species of lactobacilli decreased linearly with
      increases in the concentration of dissolved solids (sugars) in liquid growth
      medium. This was most likely due to the osmotic stress exerted by the sugars on
      the bacteria. The reduction in growth rates corresponded to decreased lactic acid
      production. Medium pH was another factor studied. As the medium pH decreased from
      5.5 to 4.0, there was a reduction in the specific growth rate of lactobacilli and
      a corresponding decrease in the lactic acid produced. In contrast, medium pH did
      not have any significant effect on the specific growth rate of yeast at any
      particular concentration of dissolved solids in the medium. However, medium pH
      had a significant (P < 0.001) effect on ethanol production. A medium pH of 5.5
      resulted in maximal ethanol production in all media with different concentrations
      of dissolved solids. When the data were analyzed as a 4 (pH levels) by 4
      (concentrations of dissolved solids) factorial experiment, there was no
      synergistic effect (P > 0.2923) observed between pH of the medium and
      concentration of dissolved solids of the medium in reducing bacterial growth and
      metabolism. The data suggest that reduction of initial medium pH to 4.0 for the
      control of lactobacilli during ethanol production is not a good practice as there
      is a reduction (P < 0.001) in the ethanol produced by the yeast at pH 4.0.
      Setting the mash (medium) with > or =30% (wt/vol) dissolved solids at a pH of 5.0
      to 5.5 will minimize the effects of bacterial contamination and maximize ethanol
      production by yeast.

PMID- 15870307
TI  - Balamuthia mandrillaris, free-living ameba and opportunistic agent of
      encephalitis, is a potential host for Legionella pneumophila bacteria.
AB  - Balamuthia mandrillaris is a free-living ameba and an opportunistic agent of
      granulomatous encephalitis in humans and other mammalian species. Other free
      living amebas, such as Acanthamoeba and Hartmannella, can provide a niche for
      intracellular survival of bacteria, including the causative agent of
      Legionnaires' disease, Legionella pneumophila. Infection of amebas by L.
      pneumophila enhances the bacterial infectivity for mammalian cells and lung
      tissues. Likewise, the pathogenicity of amebas may be enhanced when they host
      bacteria. So far, the colonization of B. mandrillaris by bacteria has not been
      convincingly shown. In this study, we investigated whether this ameba could host
      L. pneumophila bacteria. Our experiments showed that L. pneumophila could
      initiate uptake by B. mandrillaris and could replicate within the ameba about 4
      to 5 log cycles from 24 to 72 h after infection. On the other hand, a dotA
      mutant, known to be unable to propagate in Acanthamoeba castellanii, also did not
      replicate within B. mandrillaris. Approaching completion of the intracellular
      cycle, L. pneumophila wild-type bacteria were able to destroy their ameboid
      hosts. Observations by light microscopy paralleled our quantitative data and
      revealed the rounding, collapse, clumping, and complete destruction of the
      infected amebas. Electron microscopic studies unveiled the replication of the
      bacteria in a compartment surrounded by a structure resembling rough endoplasmic
      reticulum. The course of intracellular infection, the degree of bacterial
      multiplication, and the ultrastructural features of a L. pneumophila-infected B.
      mandrillaris ameba resembled those described for other amebas hosting Legionella
      bacteria. We hence speculate that B. mandrillaris might serve as a host for
      bacteria in its natural environment.

PMID- 15870308
TI  - Quantification of enterococci and human adenoviruses in environmental samples by
      real-time PCR.
AB  - Pathogenic bacteria and enteric viruses can be introduced into the environment
      via human waste discharge. Methods for rapid detection and quantification of
      human viruses and fecal indicator bacteria in water are urgently needed to
      prevent human exposure to pathogens through drinking and recreational waters.
      Here we describe the development of two real-time PCR methods to detect and
      quantify human adenoviruses and enterococci in environmental waters. For real
      time quantification of enterococci, a set of primers and a probe targeting the
      23S rRNA gene were used. The standard curve generated using Enterococcus faecalis
      genomic DNA was linear over a 7-log-dilution series. Serial dilutions of E.
      faecalis suspensions resulted in a lower limit of detection (LLD) of 5
      CFU/reaction. To develop real-time PCR for adenoviruses, degenerate primers and a
      Taqman probe targeting a 163-bp region of the adenovirus hexon gene were designed
      to specifically amplify 14 different serotypes of human adenoviruses, including
      enteric adenovirus serotype 40 and 41. The standard curve generated was linear
      over a 5-log-dilution series, and the LLD was 100 PFU/reaction using serial
      dilutions of purified adenoviral particles of serotype 40. Both methods were
      optimized to be applicable to environmental samples. The real-time PCR methods
      showed a greater sensitivity in detection of adenoviruses in sewage samples than
      the viral plaque assay and in detection of enterococci in coastal waters than the
      bacterial culture method. However, enterococcus real-time PCR overestimated the
      number of bacteria in chlorinated sewage in comparison with the bacterial culture
      method. Overall, the ability via real-time PCR to detect enterococci and
      adenoviruses rapidly and quantitatively in the various environmental samples
      represents a considerable advancement and a great potential for environmental
      applications.

PMID- 15870309
TI  - Deuterium-resistant algal cell line for D labeling of heterotrophs expresses
      enhanced level of Hsp60 in D2O medium.
AB  - Fully deuterated components from autotrophic cell lysate are useful materials for
      labeling of heterotrophs with deuterium. To facilitate the faster production of
      deuterated algal lysate, we selected a mutant Chlorella strain that grows faster
      in heavy water than the wild type. The mutant DR-17 was found to have a higher
      level of Hsp60 and an elevated level of protein synthesis. We previously isolated
      a deuterium-resistant yeast cell line that was also found to express elevated
      level of Hsp70 (K. Unno, T. Kishido, M. Morioka, S. Okada, and N. Oku, Biol.
      Pharm. Bull. 26:799-802, 2003). This suggests that the overexpression of heat
      shock proteins is required to compensate for the deuterium isotope effect.

PMID- 15870310
TI  - Relationship between bacterioplankton richness, respiration, and production in
      the Southern North Sea.
AB  - We investigated the relationship between bacterioplankton production (BP),
      respiration (BR), and community composition measured by terminal restriction
      fragment length polymorphism in the southern North Sea over a seasonal cycle.
      Major changes in bacterioplankton richness were apparent from April to December.
      While cell-specific BP decreased highly significantly with increasing
      bacterioplankton richness, cell-specific BR was found to be variable along the
      richness gradient, suggesting that bacterioplankton respiration is rather
      independent from shifts in the bacterial community composition. As a consequence,
      the bacterial growth efficiency [BGE = BP/(BP + BR)] was negatively related to
      bacterioplankton richness, explaining approximately 43% of the variation in BGE.
      Our results indicate that despite the observed shifts in the community
      composition, the main function of the bacterioplankton, the remineralization of
      dissolved organic carbon to CO(2), is rather stable.

PMID- 15870311
TI  - Influence of dietary zinc oxide and copper sulfate on the gastrointestinal
      ecosystem in newly weaned piglets.
AB  - Dietary doses of 2,500 ppm ZnO-Zn reduced bacterial activity (ATP accumulation)
      in digesta from the gastrointestinal tracts of newly weaned piglets compared to
      that in animals receiving 100 ppm ZnO-Zn. The amounts of lactic acid bacteria
      (MRS counts) and lactobacilli (Rogosa counts) were reduced, whereas coliforms
      (MacConkey counts) and enterococci (Slanetz counts, red colonies) were more
      numerous in animals receiving the high ZnO dose. Based on 16S rRNA gene
      sequencing, the colonies on MRS were dominated by three phylotypes, tentatively
      identified as Lactobacillus amylovorus (OTU171), Lactobacillus reuteri (OTU173),
      and Streptococcus alactolyticus (OTU180). The colonies on Rogosa plates were
      dominated by the two Lactobacillus phylotypes only. Terminal restriction fragment
      length polymorphism analysis supported the observations of three phylotypes of
      lactic acid bacteria dominating in piglets receiving the low ZnO dose and of
      coliforms and enterococci dominating in piglets receiving the high ZnO dose.
      Dietary doses of 175 ppm CuSO(4)-Cu also reduced MRS and Rogosa counts of stomach
      contents, but for these animals, the numbers of coliforms were reduced in the
      cecum and the colon. The influence of ZnO on the gastrointestinal microbiota
      resembles the working mechanism suggested for some growth-promoting antibiotics,
      namely, the suppression of gram-positive commensals rather than potentially
      pathogenic gram-negative organisms. Reduced fermentation of digestible nutrients
      in the proximal part of the gastrointestinal tract may render more energy
      available for the host animal and contribute to the growth-promoting effect of
      high dietary ZnO doses. Dietary CuSO(4) inhibited the coliforms and thus
      potential pathogens as well, but overall the observed effect of CuSO(4) was
      limited compared to that of ZnO.

PMID- 15870312
TI  - Seasonal response of stream biofilm communities to dissolved organic matter and
      nutrient enrichments.
AB  - Dissolved organic matter (DOM) and inorganic nutrients may affect microbial
      communities in streams, but little is known about the impact of these factors on
      specific taxa within bacterial assemblages in biofilms. In this study, nutrient
      diffusing artificial substrates were used to examine bacterial responses to DOM
      (i.e., glucose, leaf leachate, and algal exudates) and inorganic nutrients
      (nitrate and phosphate singly and in combination). Artificial substrates were
      deployed for five seasons, from summer 2002 to summer 2003, in a northeastern
      Ohio stream. Differences were observed in the responses of bacterial taxa
      examined to various DOM and inorganic nutrient treatments, and the response
      patterns varied seasonally, indicating that resources that limit the bacterial
      communities change over time. Overall, the greatest responses were to labile, low
      molecular-weight DOM (i.e., glucose) at times when chlorophyll a concentrations
      were low due to scouring during significant storm events. Different types of DOM
      and inorganic nutrients induced various responses among bacterial taxa in the
      biofilms examined, and these responses would not have been apparent if they were
      examined at the community level or if seasonal changes were not taken into
      account.

PMID- 15870313
TI  - Production of rhamnolipids by Pseudomonas chlororaphis, a nonpathogenic
      bacterium.
AB  - Rhamnolipids, naturally occurring biosurfactants constructed of rhamnose sugar
      molecules and beta-hydroxyalkanoic acids, have a wide range of potential
      commercial applications. In the course of a survey of 33 different bacterial
      isolates, we have identified, using a phenotypic assay for rhamnolipid
      production, a strain of the nonpathogenic bacterial species Pseudomonas
      chlororaphis that is capable of producing rhamnolipids. Rhamnolipid production by
      P. chlororaphis was achieved by growth at room temperature in static cultures of
      a mineral salts medium containing 2% glucose. We obtained yields of roughly 1
      g/liter of rhamnolipids, an amount comparable to the production levels reported
      in Pseudomonas aeruginosa grown with glucose as the carbon source. The
      rhamnolipids produced by P. chlororaphis appear to be exclusively the mono
      rhamnolipid form. The most prevalent molecular species had one monounsaturated
      hydroxy fatty acid of 12 carbons and one saturated hydroxy fatty acid of 10
      carbons. P. chlororaphis, a nonpathogenic saprophyte of the soil, is currently
      employed as a biocontrol agent against certain types of plant fungal diseases.
      The pathogenic nature of all bacteria previously known to produce rhamnolipids
      has been a major obstacle to commercial production of rhamnolipids. The use of P.
      chlororaphis therefore greatly simplifies this matter by removing the need for
      containment systems and stringent separation processes in the production of
      rhamnolipids.

PMID- 15870314
TI  - Metabolic network analysis of Streptomyces tenebrarius, a Streptomyces species
      with an active entner-doudoroff pathway.
AB  - Streptomyces tenebrarius is an industrially important microorganism, producing an
      antibiotic complex that mainly consists of the aminoglycosides apramycin,
      tobramycin carbamate, and kanamycin B carbamate. When S. tenebrarius is used for
      industrial tobramycin production, kanamycin B carbamate is an unwanted by
      product. The two compounds differ only by one hydroxyl group, which is present in
      kanamycin carbamate but is reduced during biosynthesis of tobramycin. (13)C
      metabolic flux analysis was used for elucidating connections between the primary
      carbon metabolism and the composition of the antibiotic complex. Metabolic flux
      maps were constructed for the cells grown on minimal medium with glucose or with
      a glucose-glycerol mixture as the carbon source. The addition of glycerol, which
      is more reduced than glucose, led to a three-times-greater reduction of the
      kanamycin portion of the antibiotic complex. The labeling indicated an active
      Entner-Doudoroff (ED) pathway, which was previously considered to be
      nonfunctional in Streptomyces. The activity of the pentose phosphate (PP) pathway
      was low (10 to 20% of the glucose uptake rate). The fluxes through Embden
      Meyerhof-Parnas (EMP) and ED pathways were almost evenly distributed during the
      exponential growth on glucose. During the transition from growth phase to
      production phase, a metabolic shift was observed, characterized by a decreased
      flux through the ED pathway and increased fluxes through the EMP and PP pathways.
      Higher specific NADH and NADPH production rates were calculated in the
      cultivation on glucose-glycerol, which was associated with a lower percentage of
      nonreduced antibiotic kanamycin B carbamate.

PMID- 15870315
TI  - Contribution of Archaea to total prokaryotic production in the deep Atlantic
      Ocean.
AB  - Fluorescence in situ hybridization (FISH) in combination with polynucleotide
      probes revealed that the two major groups of planktonic Archaea (Crenarchaeota
      and Euryarchaeota) exhibit a different distribution pattern in the water column
      of the Pacific subtropical gyre and in the Antarctic Circumpolar Current system.
      While Euryarchaeota were found to be more dominant in nearsurface waters,
      Crenarchaeota were relatively more abundant in the mesopelagic and bathypelagic
      waters. We determined the abundance of archaea in the mesopelagic and
      bathypelagic North Atlantic along a south-north transect of more than 4,000 km.
      Using an improved catalyzed reporter deposition-FISH (CARD-FISH) method and
      specific oligonucleotide probes, we found that archaea were consistently more
      abundant than bacteria below a 100-m depth. Combining microautoradiography with
      CARD-FISH revealed a high fraction of metabolically active cells in the deep
      ocean. Even at a 3,000-m depth, about 16% of the bacteria were taking up leucine.
      The percentage of Euryarchaeota and Crenarchaeaota taking up leucine did not
      follow a specific trend, with depths ranging from 6 to 35% and 3 to 18%,
      respectively. The fraction of Crenarchaeota taking up inorganic carbon increased
      with depth, while Euryarchaeota taking up inorganic carbon decreased from 200 m
      to 3,000 m in depth. The ability of archaea to take up inorganic carbon was used
      as a proxy to estimate archaeal cell production and to compare this archaeal
      production with total prokaryotic production measured via leucine incorporation.
      We estimate that archaeal production in the mesopelagic and bathypelagic North
      Atlantic contributes between 13 to 27% to the total prokaryotic production in the
      oxygen minimum layer and 41 to 84% in the Labrador Sea Water, declining to 10 to
      20% in the North Atlantic Deep Water. Thus, planktonic archaea are actively
      growing in the dark ocean although at lower growth rates than bacteria and might
      play a significant role in the oceanic carbon cycle.

PMID- 15870316
TI  - Reduced proteolysis of secreted gelatin and Yps1-mediated alpha-factor leader
      processing in a Pichia pastoris kex2 disruptant.
AB  - Heterologous proteins secreted by yeast and fungal expression hosts are
      occasionally degraded at basic amino acids. We cloned Pichia pastoris homologs of
      the Saccharomyces cerevisiae basic residue-specific endoproteases Kex2 and Yps1
      to evaluate their involvement in the degradation of a secreted mammalian gelatin.
      Disruption of the P. pastoris KEX2 gene prevented proteolysis of the foreign
      protein at specific monoarginylic sites. The S. cerevisiae alpha-factor
      preproleader used to direct high-level gelatin secretion was correctly processed
      at its dibasic site in the absence of the prototypical proprotein convertase
      Kex2. Disruption of the YPS1 gene had no effect on gelatin degradation or
      processing of the alpha-factor propeptide. When both the KEX2 and YPS1 genes were
      disrupted, correct precursor maturation no longer occurred. The different
      substrate specificities of both proteases and their mutual redundancy for
      propeptide processing indicate that P. pastoris kex2 and yps1 single-gene
      disruptants can be used for the alpha-factor leader-directed secretion of
      heterologous proteins otherwise degraded at basic residues.

PMID- 15870317
TI  - Quantitative real-time PCR assays to identify and quantify fecal Bifidobacterium
      species in infants receiving a prebiotic infant formula.
AB  - A healthy intestinal microbiota is considered to be important for priming of the
      infants' mucosal and systemic immunity. Breast-fed infants typically have an
      intestinal microbiota dominated by different Bifidobacterium species. It has been
      described that allergic infants have different levels of specific Bifidobacterium
      species than healthy infants. For the accurate quantification of Bifidobacterium
      adolescentis, Bifidobacterium angulatum, Bifidobacterium bifidum, Bifidobacterium
      breve, Bifidobacterium catenulatum, Bifidobacterium dentium, Bifidobacterium
      infantis, and Bifidobacterium longum in fecal samples, duplex 5' nuclease assays
      were developed. The assays, targeting rRNA gene intergenic spacer regions, were
      validated and compared with conventional PCR and fluorescent in situ
      hybridization methods. The 5' nuclease assays were subsequently used to determine
      the relative amounts of different Bifidobacterium species in fecal samples from
      infants receiving a standard formula or a standard formula supplemented with
      galacto- and fructo-oligosaccharides (OSF). A breast-fed group was studied in
      parallel as a reference. The results showed a significant increase in the total
      amount of fecal bifidobacteria (54.8% +/- 9.8% to 73.4% +/- 4.0%) in infants
      receiving the prebiotic formula (OSF), with a diversity of Bifidobacterium
      species similar to breast-fed infants. The intestinal microbiota of infants who
      received a standard formula seems to resemble a more adult-like distribution of
      bifidobacteria and contains relatively more B. catenulatum and B. adolescentis
      (2.71% +/- 1.92% and 8.11% +/- 4.12%, respectively, versus 0.15% +/- 0.11% and
      1.38% +/- 0.98% for the OSF group). In conclusion, the specific prebiotic infant
      formula used induces a fecal microbiota that closely resembles the microbiota of
      breast-fed infants also at the level of the different Bifidobacterium species.

PMID- 15870318
TI  - Nested PCR-denaturing gradient gel electrophoresis approach to determine the
      diversity of sulfate-reducing bacteria in complex microbial communities.
AB  - Here, we describe a three-step nested-PCR-denaturing gradient gel electrophoresis
      (DGGE) strategy to detect sulfate-reducing bacteria (SRB) in complex microbial
      communities from industrial bioreactors. In the first step, the nearly complete
      16S rRNA gene was amplified using bacterial primers. Subsequently, this product
      was used as a template in a second PCR with group-specific SRB primers. A third
      round of amplification was conducted to obtain fragments suitable for DGGE. The
      largest number of bands was observed in DGGE patterns of products obtained with
      primers specific for the Desulfovibrio-Desulfomicrobium group, indicating a large
      diversity of these SRBs. In addition, members of other phylogenetic SRB groups,
      i.e., Desulfotomaculum, Desulfobulbus, and Desulfococcus-Desulfonema
      Desulfosarcina, were detected. Bands corresponding to Desulfobacterium and
      Desulfobacter were not detected in the bioreactor samples. Comparative sequence
      analysis of excised DGGE bands revealed the identity of the community members.
      The developed three-step PCR-DGGE strategy is a welcome tool for studying the
      diversity of sulfate-reducing bacteria.

PMID- 15870319
TI  - Chemical forms of selenium in the metal-resistant bacterium Ralstonia
      metallidurans CH34 exposed to selenite and selenate.
AB  - Ralstonia metallidurans CH34, a soil bacterium resistant to a variety of metals,
      is known to reduce selenite to intracellular granules of elemental selenium
      (Se(0)). We have studied the kinetics of selenite (Se(IV)) and selenate (Se(VI))
      accumulation and used X-ray absorption spectroscopy to identify the accumulated
      form of selenate, as well as possible chemical intermediates during the
      transformation of these two oxyanions. When introduced during the lag phase, the
      presence of selenite increased the duration of this phase, as previously
      observed. Selenite introduction was followed by a period of slow uptake, during
      which the bacteria contained Se(0) and alkyl selenide in equivalent proportions.
      This suggests that two reactions with similar kinetics take place: an
      assimilatory pathway leading to alkyl selenide and a slow detoxification pathway
      leading to Se(0). Subsequently, selenite uptake strongly increased (up to 340 mg
      Se per g of proteins) and Se(0) was the predominant transformation product,
      suggesting an activation of selenite transport and reduction systems after
      several hours of contact. Exposure to selenate did not induce an increase in the
      lag phase duration, and the bacteria accumulated approximately 25-fold less Se
      than when exposed to selenite. Se(IV) was detected as a transient species in the
      first 12 h after selenate introduction, Se(0) also occurred as a minor species,
      and the major accumulated form was alkyl selenide. Thus, in the present
      experimental conditions, selenate mostly follows an assimilatory pathway and the
      reduction pathway is not activated upon selenate exposure. These results show
      that R. metallidurans CH34 may be suitable for the remediation of selenite-, but
      not selenate-, contaminated environments.

PMID- 15870320
TI  - Construction of a ColD cda promoter-based SOS-green fluorescent protein whole
      cell biosensor with higher sensitivity toward genotoxic compounds than constructs
      based on recA, umuDC, or sulA promoters.
AB  - Four different green fluorescent protein (GFP)-based whole-cell biosensors were
      created based on the DNA damage inducible SOS response of Escherichia coli in
      order to evaluate the sensitivity of individual SOS promoters toward genotoxic
      substances. Treatment with the known carcinogen N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) revealed that the promoter for the ColD plasmid-borne cda
      gene had responses 12, 5, and 3 times greater than the recA, sulA, and umuDC
      promoters, respectively, and also considerably higher sensitivity. Furthermore,
      we showed that when the SOS-GFP construct was introduced into an E. coli host
      deficient in the tolC gene, the minimal detection limits toward mitomycin C,
      MNNG, nalidixic acid, and formaldehyde were lowered to 9.1 nM, 0.16 microM, 1.1
      microM, and 141 microM, respectively, which were two to six times lower than
      those in the wild-type strain. This study thus presents a new SOS-GFP whole-cell
      biosensor which is not only able to detect minute levels of genotoxins but, due
      to its use of the green fluorescent protein, also a reporter system which should
      be applicable in high-throughput screening assays as well as a wide variety of in
      situ detection studies.

PMID- 15870321
TI  - Construction, analysis, and beta-glucanase screening of a bacterial artificial
      chromosome library from the large-bowel microbiota of mice.
AB  - A metagenomic (community genomic) library consisting of 5,760 bacterial
      artificial chromosome clones was prepared in Escherichia coli DH10B from DNA
      extracted from the large-bowel microbiota of BALB/c mice. DNA inserts detected in
      61 randomly chosen clones averaged 55 kbp (range, 8 to 150 kbp) in size. A
      functional screen of the library for beta-glucanase activity was conducted using
      lichenin agar plates and Congo red solution. Three clones with beta-glucanase
      activity were detected. The inserts of these three clones were sequenced and
      annotated. Open reading frames (ORF) that encoded putative proteins with identity
      to glucanolytic enzymes (lichenases and laminarinases) were detected by reference
      to databases. Other putative genes were detected, some of which might have a role
      in environmental sensing, nutrient acquisition, or coaggregation. The insert DNA
      from two clones probably originated from uncultivated bacteria because the ORF
      had low sequence identity with database entries, but the genes associated with
      the remaining clone resembled sequences reported in Bacteroides species.

PMID- 15870322
TI  - Use of stochastic models to assess the effect of environmental factors on
      microbial growth.
AB  - We present a novel application of a stochastic ecological model to the study and
      analysis of microbial growth dynamics as influenced by environmental conditions
      in an extensive experimental data set. The model proved to be useful in bridging
      the gap between theoretical ideas in ecology and an applied problem in
      microbiology. The data consisted of recorded growth curves of Escherichia coli
      grown in triplicate in a base medium with all 32 possible combinations of five
      supplements: glucose, NH(4)Cl, HCl, EDTA, and NaCl. The potential complexity of
      2(5) experimental treatments and their effects was reduced to 2(2) as just the
      metal chelator EDTA, the presumed osmotic pressure imposed by NaCl, and the
      interaction between these two factors were enough to explain the variability seen
      in the data. The statistical analysis showed that the positive and negative
      effects of the five chemical supplements and their combinations were directly
      translated into an increase or decrease in time required to attain stationary
      phase and the population size at which the stationary phase started. The
      stochastic ecological model proved to be useful, as it effectively explained and
      summarized the uncertainty seen in the recorded growth curves. Our findings have
      broad implications for both basic and applied research and illustrate how
      stochastic mathematical modeling coupled with rigorous statistical methods can be
      of great assistance in understanding basic processes in microbial ecology.

PMID- 15870323
TI  - Utilization of the plant hormone indole-3-acetic acid for growth by Pseudomonas
      putida strain 1290.
AB  - We have isolated from plant surfaces several bacteria with the ability to
      catabolize indole-3-acetic acid (IAA). One of them, isolate 1290, was able to
      utilize IAA as a sole source of carbon, nitrogen, and energy. The strain was
      identified by its 16S rRNA sequence as Pseudomonas putida. Activity of the enzyme
      catechol 1,2-dioxygenase was induced during growth on IAA, suggesting that
      catechol is an intermediate of the IAA catabolic pathway. This was in agreement
      with the observation that the oxygen uptake by IAA-grown P. putida 1290 cells was
      elevated in response to the addition of catechol. The inability of a catR mutant
      of P. putida 1290 to grow at the expense of IAA also suggests a central role for
      catechol as an intermediate in IAA metabolism. Besides being able to destroy IAA,
      strain 1290 was also capable of producing IAA in media supplemented with
      tryptophan. In root elongation assays, P. putida strain 1290 completely abolished
      the inhibitory effect of exogenous IAA on the elongation of radish roots. In
      fact, coinoculation of roots with P. putida 1290 and 1 mM concentration of IAA
      had a positive effect on root development. In coinoculation experiments on radish
      roots, strain 1290 was only partially able to alleviate the inhibitory effect of
      bacteria that in culture overproduce IAA. Our findings imply a biological role
      for strain 1290 as a sink or recycler of IAA in its association with plants and
      plant-associated bacteria.

PMID- 15870324
TI  - LuxS-based signaling affects Streptococcus mutans biofilm formation.
AB  - Streptococcus mutans is implicated as a major etiological agent in human dental
      caries, and one of the important virulence properties of this organism is its
      ability to form biofilms (dental plaque) on tooth surfaces. We examined the role
      of autoinducer-2 (AI-2) on S. mutans biofilm formation by constructing a GS-5
      luxS-null mutant. Biofilm formation by the luxS mutant in 0.5% sucrose defined
      medium was found to be markedly attenuated compared to the wild type. Scanning
      electron microscopy also revealed that biofilms of the luxS mutant formed larger
      clumps in sucrose medium compared to the parental strain. Therefore, the
      expression of glucosyltransferase genes was examined and the gtfB and gtfC genes,
      but not the gtfD gene, in the luxS mutant were upregulated in the mid-log growth
      phase. Furthermore, we developed a novel two-compartment system to monitor AI-2
      production by oral streptococci and periodontopathic bacteria. The biofilm defect
      of the luxS mutant was complemented by strains of S. gordonii, S. sobrinus, and
      S. anginosus; however, it was not complemented by S. oralis, S. salivarius, or S.
      sanguinis. Biofilm formation by the luxS mutant was also complemented by
      Porphyromonas gingivalis 381 and Actinobacillus actinomycetemcomitans Y4 but not
      by a P. gingivalis luxS mutant. These results suggest that the regulation of the
      glucosyltransferase genes required for sucrose-dependent biofilm formation is
      regulated by AI-2. Furthermore, these results provide further confirmation of
      previous proposals that quorum sensing via AI-2 may play a significant role in
      oral biofilm formation.

PMID- 15870325
TI  - Influence of top-down and bottom-up manipulations on the R-BT065 subcluster of
      beta-proteobacteria, an abundant group in bacterioplankton of a freshwater
      reservoir.
AB  - We studied the effects of nutrient availability and protistan grazing on
      bacterial dynamics and community composition (BCC) in different parts of the
      canyon-shaped Rimov reservoir (Czech Republic). The effects of protistan grazing
      on BCC were examined using a size fractionation approach. Water from the dam area
      with only bacteria (<0.8 microm), bacteria and heterotrophic nanoflagellates (<5
      microm), or whole water were incubated in situ inside dialysis bags. Top-down or
      predator manipulations (size fractionation) were also combined with bottom-up or
      resource manipulations, i.e., transplantation of samples to the middle and upper
      inflow parts of the reservoir with increased phosphorus availability. Significant
      genotypic shifts in BCC occurred with transplantation as indicated by denaturing
      gradient gel electrophoresis. Using different probes for fluorescence in situ
      hybridization, we found that 10 to 50% of total bacteria were members of the
      phylogenetically small cluster of beta-proteobacteria (targeted with the probe R
      BT065). These rod-shaped cells of very uniform size were vulnerable to predation
      but very fast growing and responded markedly to the different experimental
      manipulations. In all the grazer-free treatments, the members of the R-BT065
      cluster showed the highest net growth rates of all studied bacterial groups.
      Moreover, their relative abundance was highly correlated with bacterial bulk
      parameters and proportions of bacteria with high nucleic acid (HNA) content. In
      contrast, increasing protistan bacterivory yielded lower proportions of R-BT065
      positive and HNA bacteria substituted by increasing proportions of the class
      Actinobacteria, which profited from the enhanced protistan bacterivory.

PMID- 15870326
TI  - Adaptation of Corynebacterium glutamicum to ammonium limitation: a global
      analysis using transcriptome and proteome techniques.
AB  - Theresponse of Corynebacterium glutamicum to ammonium limitation was studied by
      transcriptional and proteome profiling of cells grown in a chemostat. Our results
      show that ammonium-limited growth of C. glutamicum results in a rearrangement of
      the cellular transport capacity, changes in metabolic pathways for nitrogen
      assimilation, amino acid biosynthesis, and carbon metabolism, as well as a
      decreased cell division. Since transcription at different growth rates was
      studied, it was possible to distinguish specific responses to ammonium limitation
      and more general, growth rate-dependent alterations in gene expression. The
      latter include a number of genes encoding ribosomal proteins and genes for
      F(o)F(1)-ATP synthase subunits.

PMID- 15870327
TI  - Application of cation-coated filter method to detection of noroviruses,
      enteroviruses, adenoviruses, and torque teno viruses in the Tamagawa River in
      Japan.
AB  - The occurrence of human enteric viruses in surface water in the Tamagawa River,
      Japan, was surveyed for 1 year, from April 2003 to March 2004. Sixty-four samples
      were collected from six sites along the river, and 500 ml of the sample was
      concentrated using the cation-coated filter method, which was developed in our
      previous study. This method showed recovery yields of 56% +/- 32% (n = 37) for
      surface water samples inoculated with polioviruses. More than one kind of tested
      virus was detected in 43 (67%) of 64 samples by TaqMan PCR. Noroviruses and
      adenoviruses were detected in a high positive ratio; 34 (53%), 28 (44%), and 29
      (45%) of 64 samples were positive for norovirus genotype 1 and genotype 2 and
      adenoviruses, respectively. The mean concentrations of norovirus genotype 1 or
      genotype 2 determined by real-time PCR were 0.087 and 0.61 genome/ml,
      respectively, showing much higher values in winter (0.21 genome/ml for genotype 1
      and 2.3 genomes/ml for genotype 2). Enteroviruses were detected by both direct
      PCR (6 of 64 samples; 9%) and cell culture PCR (2 of 64 samples; 3%). Torque teno
      viruses, emerging hepatitis viruses, were also isolated in three samples (5%).
      The concentration of total coliforms and the presence of F-specific phages showed
      a high correlation with the presence of viruses, which suggested that the
      simultaneous use of total coliforms and F-specific phages as indicators of
      surface water may work to monitor viral contamination.

PMID- 15870328
TI  - Processive endoglucanase active in crystalline cellulose hydrolysis by the brown
      rot basidiomycete Gloeophyllum trabeum.
AB  - Brown rot basidiomycetes have long been thought to lack the processive cellulases
      that release soluble sugars from crystalline cellulose. On the other hand, these
      fungi remove all of the cellulose, both crystalline and amorphous, from wood when
      they degrade it. To resolve this discrepancy, we grew Gloeophyllum trabeum on
      microcrystalline cellulose (Avicel) and purified the major glycosylhydrolases it
      produced. The most abundant extracellular enzymes in these cultures were a 42-kDa
      endoglucanase (Cel5A), a 39-kDa xylanase (Xyn10A), and a 28-kDa endoglucanase
      (Cel12A). Cel5A had significant Avicelase activity--4.5 nmol glucose equivalents
      released/min/mg protein. It is a processive endoglucanase, because it hydrolyzed
      Avicel to cellobiose as the major product while introducing only a small
      proportion of reducing sugars into the remaining, insoluble substrate. Therefore,
      since G. trabeum is already known to produce a beta-glucosidase, it is now clear
      that this brown rot fungus produces enzymes capable of yielding assimilable
      glucose from crystalline cellulose.

PMID- 15870329
TI  - Reduced genetic variation occurs among genes of the highly clonal plant pathogen
      Xanthomonas axonopodis pv. vesicatoria, including the effector gene avrBs2.
AB  - The bacterial plant pathogen Xanthomonas axonopodis pv. vesicatoria, also known
      as Xanthomonas campestris pv. vesicatoria group A, is the causal agent of
      bacterial spot in pepper and tomato. In order to test different models that may
      explain the coevolution of avrBs2 with its host plants, we sequenced avrBs2 and
      six chromosomal loci (total of 5.5 kb per strain) from a global sample of 55 X.
      axonopodis pv. vesicatoria strains collected from diseased peppers. We found an
      extreme lack of genetic variation among all X. axonopodis pv. vesicatoria genomic
      loci (average nucleotide diversity, pi = 9.1 x 10(-5)), including avrBs2. This
      lack of diversity is consistent with X. axonopodis pv. vesicatoria having
      undergone a recent population bottleneck and/or selective sweep followed by
      population expansion. Coalescent analysis determined that approximately 1.4 x
      10(4) to 7.16 x 10(4) bacterial generations have passed since the most recent
      common ancestor (MRCA) of the current X. axonopodis pv. vesicatoria population.
      Assuming a range of 50 to 500 bacterial generations per year, only 28 to 1,432
      years have passed since the MRCA. This time frame coincides with human
      intervention with the pathogen's host plants, from domestication to modern
      agricultural practices. Examination of 19 mutated (loss-of-function) avrBs2
      alleles detected nine classes of mutations. All mutations affected protein
      coding, while no synonymous changes were found. The nature of at least one of the
      avrBs2 mutations suggests that it may be possible to observe one stage of an
      evolutionary arms race as X. axonopodis pv. vesicatoria responds to selection
      pressure to alter avrBs2 to escape host plant resistance.

PMID- 15870330
TI  - Potential role of Diploscapter sp. strain LKC25, a bacterivorous nematode from
      soil, as a vector of food-borne pathogenic bacteria to preharvest fruits and
      vegetables.
AB  - Diploscapter, a thermotolerant, free-living soil bacterial-feeding nematode
      commonly found in compost, sewage, and agricultural soil in the United States,
      was studied to determine its potential role as a vehicle of Salmonella enterica
      serotype Poona, enterohemorrhagic Escherichia coli O157:H7, and Listeria
      monocytogenes in contaminating preharvest fruits and vegetables. The ability of
      Diploscapter sp. strain LKC25 to survive on agar media, in cow manure, and in
      composted turkey manure and to be attracted to, ingest, and disperse food-borne
      pathogens inoculated into soil or a mixture of soil and composted turkey manure
      was investigated. Diploscapter sp. strain LKC25 survived and reproduced in lawns
      of S. enterica serotype Poona, E. coli O157:H7, and L. monocytogenes on agar
      media and in cow manure and composted turkey manure. Attraction of Diploscapter
      sp. strain LKC25 to colonies of pathogenic bacteria on tryptic soy agar within
      10, 20, 30, and 60 min and 24 h was determined. At least 85% of the worms
      initially placed 0.5 to 1 cm away from bacterial colonies migrated to the
      colonies within 1 h. Within 24 h, > or =90% of the worms were embedded in
      colonies. The potential of Diploscapter sp. strain LKC25 to shed pathogenic
      bacteria after exposure to bacteria inoculated into soil or a mixture of soil and
      composted turkey manure was investigated. Results indicate that Diploscapter sp.
      strain LKC25 can shed pathogenic bacteria after exposure to pathogens in these
      milieus. They also demonstrate its potential to serve as a vector of food-borne
      pathogenic bacteria in soil, with or without amendment with compost, to the
      surface of preharvest fruits and vegetables in contact with soil.

PMID- 15870331
TI  - Antimicrobial resistance profiles of Campylobacter jejuni isolates from wild
      birds in Sweden.
AB  - In order to determine the occurrence and frequency of resistant strains of the
      bacterium Campylobacter jejuni and to establish baseline MICs in isolates from an
      environmental reservoir, the resistance profiles of 10 antimicrobial substances
      were determined for 137 C. jejuni isolates from wild birds in Sweden. Observed
      MICs were generally low, with only low to moderate incidence of resistance to the
      tested compounds. One isolate, however, was resistant to nalidixic acid and
      ciprofloxacin, indicating that quinolone-resistant genotypes of C. jejuni have
      the potential to spread to wild bird hosts.

PMID- 15870332
TI  - Identification and phenotypic characterization of Sphingomonas wittichii strain
      RW1 by peptide mass fingerprinting using matrix-assisted laser desorption
      ionization-time of flight mass spectrometry.
AB  - Mass spectrometry is a potentially attractive means of monitoring the survival
      and efficacy of bioaugmentation agents, such as the dioxin-mineralizing bacterium
      Sphingomonas wittichii strain RW1. The biotransformation activity of RW1
      phenotypes is determined primarily by the presence and concentration of the
      dioxin dioxygenase, an enzyme initiating the degradation of both dibenzo-p-dioxin
      and dibenzofuran (DF). We explored the possibility of identifying and
      characterizing putative cultures of RW1 by peptide mass fingerprinting (PMF)
      targeting this characteristic phenotypic biomarker. The proteome from cells of
      RW1--grown on various media in the presence and absence of DF--was partially
      purified, tryptically digested, and analyzed using matrix-assisted laser
      desorption ionization-time of flight mass spectrometry. Mascot online database
      queries allowed statistically significant identification of RW1 in disrupted,
      digested cells (P < 0.01 to 0.05) and in digested whole-cell extracts (P <
      0.00001 to 0.05) containing hundreds of proteins, as determined by two
      dimensional gel electrophoresis. Up to 14 peptide ions of the alpha subunit of
      the dioxin dioxygenase (43% protein coverage) were detected in individual
      samples. A minimum of 10(7) DF-grown cells was required to identify dioxin
      degradation-enabled phenotypes. The technique hinges on the detection of multiple
      characteristic peptides of a biomarker that can reveal at once the identity and
      phenotypic properties of the microbial host expressing the protein. The results
      demonstrate the power of PMF of minimally processed microbial cultures as a
      sensitive and specific technique for the positive identification and phenotypic
      characterization of certain microorganisms used in biotechnology and
      bioremediation.

PMID- 15870333
TI  - Heterologous expression of novobiocin and clorobiocin biosynthetic gene clusters.
AB  - A method was developed for the heterologous expression of biosynthetic gene
      clusters in different Streptomyces strains and for the modification of these
      clusters by single or multiple gene replacements or gene deletions with
      unprecedented speed and versatility. Lambda-Red-mediated homologous recombination
      was used for genetic modification of the gene clusters, and the attachment site
      and integrase of phage phiC31 were employed for the integration of these clusters
      into the heterologous hosts. This method was used to express the gene clusters of
      the aminocoumarin antibiotics novobiocin and clorobiocin in the well-studied
      strains Streptomyces coelicolor and Streptomyces lividans, which, in contrast to
      the natural producers, can be easily genetically manipulated. S. coelicolor M512
      derivatives produced the respective antibiotic in yields comparable to those of
      natural producer strains, whereas S. lividans TK24 derivatives were at least five
      times less productive. This method could also be used to carry out functional
      investigations. Shortening of the cosmids' inserts showed which genes are
      essential for antibiotic production.

PMID- 15870334
TI  - Distribution of genes for synthesis of trehalose and Mannosylglycerate in Thermus
      spp. and direct correlation of these genes with halotolerance.
AB  - In this study we correlate the presence of genes leading to the synthesis of
      trehalose and mannosylglycerate (MG) in 17 strains of the genus Thermus with the
      ability of the strains to grow and accumulate these compatible solutes in a
      defined medium containing NaCl. The two sets of genes, namely, otsA/otsB for the
      synthesis of trehalose and mpgS/mpgP for the synthesis of MG, were necessary for
      the growth of Thermus thermophilus in a defined medium containing up to 6% NaCl.
      Strains lacking a complete otsA gene did not grow in defined medium containing
      >2% NaCl. One strain of T. thermophilus lacking the genes for the synthesis of MG
      did not grow in a medium with >1% NaCl. We did not identify any of these genes in
      the type strains of the other seven species of Thermus, and none of those strains
      grew in defined medium with 1% NaCl. The results strongly indicate that the
      combined accumulation of trehalose and MG is required for optimal osmotic
      adjustment.

PMID- 15870335
TI  - Phenotypic and genotypic selection of microbiota surviving under dental
      restorations.
AB  - The effects of sealing infected carious dentine below dental restorations on the
      phenotypic and genotypic diversity of the surviving microbiota was investigated.
      It was hypothesized that the microbiota would be subject to nutrient limitation
      or nutrient simplification, as it would no longer have access to dietary
      components or salivary secretion for growth. The available nutrients would be
      limited primarily to serum proteins passing from the pulp through the patent
      dentinal tubules to the infected dentine. Ten lesions were treated, and infected
      dentine was sealed below dental restorations for approximately 5 months.
      Duplicate standardized samples of infected dentine were taken at baseline and
      after the removal of the restorations. The baseline microbiota were composed
      primarily of Lactobacillus spp., Streptococcus mutans, Streptococcus
      parasanguinis, Actinomyces israelii, and Actinomyces gerencseriae. None of these
      taxa were isolated among the microbiota of the dentine samples taken after 5
      months, which consisted of only Actinomyces naeslundii, Streptococcus oralis,
      Streptococcus intermedius, and Streptococcus mitis. The microbiota of the final
      sample exhibited a significantly (P < 0.001) increased ability to produce
      glycosidic enzymes (sialidase, beta-N-acetylglucosaminidase, and beta
      galactosidase), which liberate sugars from glycoproteins. The genotypic diversity
      of S. oralis and A. naeslundii was significantly (P = 0.002 and P = 0.001,
      respectively) reduced in the final samples. There was significantly (P < 0.001)
      greater genotypic diversity within these taxa between the pairs of dentine
      samples taken at baseline than was found in the 5-month samples, indicating that
      the dentine was more homogenous than it was at baseline. We propose that during
      the interval between placement of the restorations and their removal, the
      available nutrient, primarily serum proteins, or the relative simplicity and
      homogeneity of the nutrient supply significantly affected the surviving
      microbiota. The surviving microbiota was less complex, based on compositional,
      phenotypic, and genotypic analyses, than that isolated from carious lesions which
      were also exposed to salivary secretions and pH perturbations.

PMID- 15870336
TI  - Heme-dependent rubber oxygenase RoxA of Xanthomonas sp. cleaves the carbon
      backbone of poly(cis-1,4-Isoprene) by a dioxygenase mechanism.
AB  - Oxidative cleavage of poly(cis-1,4-isoprene) by rubber oxygenase RoxA purified
      from Xanthomonas sp. was investigated in the presence of different combinations
      of (16)O(2), (18)O(2), H(2)(16)O, and H(2)(18)O. 12-oxo-4,8-dimethyl-trideca-4,8
      diene-1-al (ODTD; m/z 236) was the main cleavage product in the absence of (18)O
      compounds. Incorporation of one (18)O atom in ODTD was found if the cleavage
      reaction was performed in the presence of (18)O(2) and H(2)(16)O. Incubation of
      poly(cis-1,4-isoprene) (with RoxA) or of isolated unlabeled ODTD (without RoxA)
      with H(2)(18)O in the presence of (16)O(2) indicated that the carbonyl oxygen
      atoms of ODTD significantly exchanged with oxygen atoms derived from water. The
      isotope exchange was avoided by simultaneous enzymatic reduction of both carbonyl
      functions of ODTD to the corresponding dialcohol (12-hydroxy-4,8-dimethyl-trideca
      4,8-diene-1-ol (HDTD; m/z 240) during RoxA-mediated in vitro cleavage of poly(cis
      1,4-isoprene). In the presence of (18)O(2), H(2)(16)O, and alcohol
      dehydrogenase/NADH, incorporation of two atoms of (18)O into the reduced
      metabolite HDTD was found (m/z 244), revealing that RoxA cleaves rubber by a
      dioxygenase mechanism. Based on the labeling results and the presence of two
      hemes in RoxA, a model of the enzymatic cleavage mechanism of poly(cis-1,4
      isoprene) is proposed.

PMID- 15870337
TI  - Efficacy of two peroxygen-based disinfectants for inactivation of Cryptosporidium
      parvum oocysts.
AB  - Two commercial peroxygen-based disinfectants containing hydrogen peroxide plus
      either peracetic acid (Ox-Virin) or silver nitrate (Ox-Agua) were tested for
      their ability to inactivate Cryptosporidium parvum oocysts. Oocysts were obtained
      from naturally infected goat kids and exposed to concentrations of 2, 5, and 10%
      Ox-Virin or 1, 3, and 5% Ox-Agua for 30, 60, and 120 min. In vitro excystation,
      vital dyes (4',6'-diamidino-2-phenylindole and propidium iodide), and infectivity
      in neonatal BALB/c mice were used to assess the viability and infectivity of
      control and disinfectant-treated oocysts. Both disinfectants had a deleterious
      effect on the survival of C. parvum oocysts, since disinfection significantly
      reduced and in some cases eliminated their viability and infectivity. When in
      vitro assays were compared with an infectivity assay as indicators of oocyst
      inactivation, the excystation assay showed 98.6% inactivation after treatment
      with 10% Ox-Virin for 60 min, while the vital-dye assay showed 95.2% inactivation
      and the infectivity assay revealed 100% inactivation. Treatment with 3% Ox-Agua
      for 30 min completely eliminated oocyst infectivity for mice, although we were
      able to observe only 74.7% inactivation as measured by excystation assays and
      24.3% with vital dyes (which proved to be the least reliable method for
      predicting C. parvum oocyst viability). These findings indicate the potential
      efficacy of both disinfectants for C. parvum oocysts in agricultural settings
      where soil, housing, or tools might be contaminated and support the argument that
      in comparison to the animal infectivity assay, vital-dye and excystation methods
      overestimate the viability of oocysts following chemical disinfection.

PMID- 15870338
TI  - Shifts in rhizoplane communities of aquatic plants after cadmium exposure.
AB  - In this study we present the comparative molecular analysis of bacterial
      communities of the aquatic plant Lemna minor from a contaminated site (RCP) and
      from a laboratory culture (EPA), as well as each of these with the addition of
      cadmium. Plants were identified as L. minor by analysis of the rpl16 chloroplast
      region. Comparative bacterial community studies were based on the analyses of 16S
      rRNA clone libraries, each containing about 100 clones from the root surfaces of
      plants. Bacterial communities were compared at three phylogenetic levels of
      resolution. At the level of bacterial divisions, differences in diversity index
      scores between treatments, with and without cadmium within the same plant type
      (EPA or RCP), were small, indicating that cadmium had little effect. When we
      compared genera within the most dominant group, the beta-proteobacteria,
      differences between unamended and cadmium-amended libraries were much larger.
      Bacterial diversity increased upon cadmium addition for both EPA and RCP
      libraries. Analyses of diversity at the phylotype level showed parallel shifts to
      more even communities upon cadmium addition; that is, percentage changes in
      diversity indices due to cadmium addition were the same for either plant type,
      indicating that contamination history might be independent of disturbance-induced
      diversity shifts. At finer phylogenetic levels of resolution, the effects of
      cadmium addition on bacterial communities were very noticeable. This study is a
      first step in understanding the role of aquatic plant-associated microbial
      communities in phytoremediation of heavy metals.

PMID- 15870339
TI  - Variation in acid resistance among shiga toxin-producing clones of pathogenic
      Escherichia coli.
AB  - Pathogenic strains of Escherichia coli, such as E. coli O157:H7, have a low
      infectious dose and an ability to survive in acidic foods. These bacteria have
      evolved at least three distinct mechanisms of acid resistance (AR), including two
      amino acid decarboxylase-dependent systems (arginine and glutamate) and a glucose
      catabolite-repressed system. We quantified the survival rates for each AR
      mechanism separately in clinical isolates representing three groups of Shiga
      toxin-producing E. coli (STEC) clones (O157:H7, O26:H11/O111:H8, and O121:H19)
      and six commensal strains from ECOR group A. Members of the STEC clones were not
      significantly more acid resistant than the commensal strains when analyzed using
      any individual AR mechanism. The glutamate system provided the best protection in
      a highly acidic environment for all groups of isolates (<0.1 log reduction in
      CFU/ml per hour at pH 2.0). Under these conditions, there was notable variation
      in survival rates among the 30 O157:H7 strains, which depended in part on Mg(2+)
      concentration. The arginine system provided better protection at pH 2.5, with a
      range of 0.03 to 0.41 log reduction per hour, compared to the oxidative system,
      with a range of 0.13 to 0.64 log reduction per hour. The average survival rate
      for the O157:H7 clonal group was significantly less than that of the other STEC
      clones in the glutamate and arginine systems and significantly less than that of
      the O26/O111 clone in the oxidative system, indicating that this clonal group is
      not exceptionally acid resistant with these specific mechanisms.

PMID- 15870340
TI  - Application of a pH-sensitive fluoroprobe (C-SNARF-4) for pH microenvironment
      analysis in Pseudomonas aeruginosa biofilms.
AB  - An important feature of microbial biofilms is the development of four-dimensional
      physical and chemical gradients in space and time. There is need for novel
      approaches to probe these so-called microenvironments to determine their effect
      on biofilm-specific processes. In this study, we describe the use of
      seminaphthorhodafluor-4F 5-(and-6) carboxylic acid (C-SNARF-4) for pH
      microenvironment analysis in Pseudomonas aeruginosa biofilms. C-SNARF-4 is a
      fluorescent ratiometric probe that allows pH quantification independent of probe
      concentration and/or laser intensity. By confocal scanning laser microscopy, C
      SNARF-4 revealed pH heterogeneity throughout the biofilm in both the x,y and x,z
      planes, with values ranging from pH 5.6 (within the biofilm) to pH 7.0 (bulk
      fluid). pH values were typically remarkably different than those just a few
      micrometers away. Although this probe has been successfully used in a number of
      eukaryotic systems, problems have been reported which describe spectral emission
      changes as a result of macromolecular interactions with the fluorophore. To
      assess how the biofilm environment may influence fluorescent properties of the
      dye, fluorescence of C-SNARF-4 was quantified via spectrofluorometry while the
      probe was suspended in various concentrations of representative biofilm matrix
      components (i.e., proteins, polysaccharides, and bacterial cells) and growth
      medium. Surprisingly, our data demonstrate that few changes in emission spectra
      occur as a result of matrix interactions below pH 7. These studies suggest that C
      SNARF-4 can be used as a reliable indicator of pH microenvironments, which may
      help elucidate their influence on the medical and geobiological roles of natural
      biofilms.

PMID- 15870341
TI  - tir- and stx-positive Escherichia coli in stream waters in a metropolitan area.
AB  - Diarrheagenic Escherichia coli, which may include the enteropathogenic E. coli
      and the enterohemorrhagic E. coli, are a significant cause of diarrheal disease
      among infants and children in both developing and developed areas. Disease
      outbreaks related to freshwater exposure have been documented, but the presence
      of these organisms in the urban aquatic environment is not well characterized.
      From April 2002 through April 2004 we conducted weekly surveys of streams in the
      metropolitan Baltimore, Md., area for the prevalence of potentially pathogenic E.
      coli by using PCR assays targeting the tir and stx(1) and stx(2) genes. Coliforms
      testing positive for the presence of the tir gene were cultured from 653 of 1,218
      samples (53%), with a greater prevalence associated with urban, polluted streams
      than in suburban and forested watershed streams. Polluted urban streams were also
      more likely to test positive for the presence of one of the stx genes. Sequence
      analysis of the tir amplicon, as well as the entire tir gene from three isolates,
      indicated that the pathogenic E. coli present in the stream waters has a high
      degree of sequence homology with the E. coli O157:H7 serotype. Our data indicate
      that pathogenic E. coli are continually deposited into a variety of stream
      habitats and suggest that this organism may be a permanent member of the
      gastrointestinal microflora of humans and animals in the metropolitan Baltimore
      area.

PMID- 15870342
TI  - Succession of internal sulfur cycles and sulfur-oxidizing bacterial communities
      in microaerophilic wastewater biofilms.
AB  - The succession of sulfur-oxidizing bacterial (SOB) community structure and the
      complex internal sulfur cycle occurring in wastewater biofilms growing under
      microaerophilic conditions was analyzed by using a polyphasic approach that
      employed 16S rRNA gene-cloning analysis combined with fluorescence in situ
      hybridization, microelectrode measurements, and standard batch and reactor
      experiments. A complete sulfur cycle was established via S(0) accumulation within
      80 days in the biofilms in replicate. This development was generally split into
      two phases, (i) a sulfur-accumulating phase and (ii) a sulfate-producing phase.
      In the first phase (until about 40 days), since the sulfide production rate
      (sulfate-reducing activity) exceeded the maximum sulfide-oxidizing capacity of
      SOB in the biofilms, H(2)S was only partially oxidized to S(0) by mainly
      Thiomicrospira denitirificans with NO(3)(-) as an electron acceptor, leading to
      significant accumulation of S(0) in the biofilms. In the second phase, the SOB
      populations developed further and diversified with time. In particular, S(0)
      accumulation promoted the growth of a novel strain, strain SO07, which
      predominantly carried out the oxidation of S(0) to SO(4)(2-) under oxic
      conditions, and Thiothrix sp. strain CT3. In situ hybridization analysis revealed
      that the dense populations of Thiothrix (ca. 10(9) cells cm(-3)) and strain SO07
      (ca. 10(8) cells cm(-3)) were found at the sulfur-rich surface (100 microm),
      while the population of Thiomicrospira denitirificans was distributed throughout
      the biofilms with a density of ca. 10(7) to 10(8) cells cm(-3). Microelectrode
      measurements revealed that active sulfide-oxidizing zones overlapped the spatial
      distributions of different phylogenetic SOB groups in the biofilms. As a
      consequence, the sulfide-oxidizing capacities of the biofilms became high enough
      to completely oxidize all H(2)S produced by SRB to SO(4)(2-) in the second phase,
      indicating establishment of the complete sulfur cycle in the biofilms.

PMID- 15870343
TI  - DNA microarray analysis of nitrogen fixation and Fe(III) reduction in Geobacter
      sulfurreducens.
AB  - A DNA microarray representing the genome of Geobacter sulfurreducens was
      constructed for use in global gene expression profiling of cells under steady
      state conditions with acetate as the electron donor and Fe(III) or fumarate as
      the electron acceptor. Reproducible differences in transcript levels were also
      observed in comparisons between cells grown with ammonia and those fixing
      atmospheric nitrogen. There was a high correlation between changes in transcript
      levels determined with microarray analyses and an evaluation of a subset of the
      genome with quantitative PCR. As expected, cells required to fix nitrogen had
      higher levels of transcripts of genes associated with nitrogen fixation, further
      demonstrating that the microarray approach could reliably detect important
      physiological changes. Cells grown with Fe(III) as the electron acceptor had
      higher levels of transcripts for omcB, a gene coding for an outer membrane c-type
      cytochrome that is essential for Fe(III) reduction. Several other c-type
      cytochrome genes also appeared to be up-regulated. An unexpected result was
      significantly higher levels of transcripts for genes which have a role in metal
      efflux, potentially suggesting the importance of maintaining metal homeostasis
      during release of soluble metals when reducing Fe(III). A substantial proportion
      (30%) of significantly expressed genes during Fe(III) reduction were genes of
      unknown function or hypothetical proteins, suggesting differences in Fe(III)
      reduction physiology among microorganisms which perform this metabolic process.

PMID- 15870344
TI  - Production of the potent antibacterial polyketide erythromycin C in Escherichia
      coli.
AB  - An Escherichia coli strain capable of producing the potent antibiotic
      erythromycin C (Ery C) was developed by expressing 17 new heterologous genes in a
      6-deoxyerythronolide B (6dEB) producer strain. The megalomicin gene cluster was
      used as the source for the construction of two artificial operons that contained
      the genes encoding the deoxysugar biosynthetic and tailoring enzymes necessary to
      convert 6dEB to Ery C. The reconstructed mycarose operon contained the seven
      genes coding for the enzymes that convert glucose-1-phosphate (G-1-P) to TDP-L
      mycarose, a 6dEB mycarosyl transferase, and a 6dEB 6-hydroxylase. The activity of
      the pathway was confirmed by demonstrating conversion of exogenous 6dEB to 3-O
      alpha-mycarosylerythronolide B (MEB). The reconstructed desosamine operon
      contained the six genes necessary to convert TDP-4-keto-6-deoxyglucose, an
      intermediate formed in the mycarose pathway, to TDP-D-desosamine, a desosamine
      transferase, a 6dEB 12-hydroxylase, and the rRNA methyltransferase ErmE; the last
      was required to confer resistance to the host cell upon production of mature
      macrolide antibiotics. The activity of this pathway was demonstrated by
      conversion of MEB to Ery C. When the mycarose and desosamine operons were
      expressed in an E. coli strain engineered to synthesize 6dEB, Ery C and Ery D
      were produced. The successful production of Ery C in E. coli shows the
      potentiality of this model microorganism to synthesize novel 6-deoxysugars and to
      produce bioactive glycosylated compounds and also establishes the basis for the
      future use of E. coli both in the production of new glycosylated polyketides and
      for the generation of novel bioactive compounds through combinatorial
      biosynthesis.

PMID- 15870345
TI  - Uptake of CdSe and CdSe/ZnS quantum dots into bacteria via purine-dependent
      mechanisms.
AB  - Quantum dots (QDs) rendered water soluble for biological applications are usually
      passivated by several inorganic and/or organic layers in order to increase
      fluorescence yield. However, these coatings greatly increase the size of the
      particle, making uptake by microorganisms impossible. We find that adenine- and
      AMP-conjugated QDs are able to label bacteria only if the particles are <5 nm in
      diameter. Labeling is dependent upon purine-processing mechanisms, as mutants
      lacking single enzymes demonstrate a qualitatively different signal than do wild
      type strains. This is shown for two example species, one gram negative and one
      gram positive. Wild-type Bacillus subtilis incubated with QDs conjugated to
      adenine are strongly fluorescent; very weak signal is seen in mutant cells
      lacking either adenine deaminase or adenosine phosphoribosyltransferase.
      Conversely, QD-AMP conjugates label mutant strains more efficiently than the wild
      type. In Escherichia coli, QD conjugates are taken up most strongly by adenine
      auxotrophs and are extruded from the cells over a time course of hours. No
      fluorescent labeling is seen in killed bacteria or in the presence of EDTA or an
      excess of unlabeled adenine, AMP, or hypoxanthine. Spectroscopy and electron
      microscopy suggest that QDs of <5 nm can enter the cells whole, probably by means
      of oxidative damage to the cell membrane which is aided by light.

PMID- 15870346
TI  - New resistance mechanism in Helicoverpa armigera threatens transgenic crops
      expressing Bacillus thuringiensis Cry1Ac toxin.
AB  - In Australia, the cotton bollworm, Helicoverpa armigera, has a long history of
      resistance to conventional insecticides. Transgenic cotton (expressing the
      Bacillus thuringiensis toxin Cry1Ac) has been grown for H. armigera control since
      1996. It is demonstrated here that a population of Australian H. armigera has
      developed resistance to Cry1Ac toxin (275-fold). Some 70% of resistant H.
      armigera larvae were able to survive on Cry1Ac transgenic cotton (Ingard) The
      resistance phenotype is inherited as an autosomal semidominant trait. Resistance
      was associated with elevated esterase levels, which cosegregated with resistance.
      In vitro studies employing surface plasmon resonance technology and other
      biochemical techniques demonstrated that resistant strain esterase could bind to
      Cry1Ac protoxin and activated toxin. In vivo studies showed that Cry1Ac-resistant
      larvae fed Cy1Ac transgenic cotton or Cry1Ac-treated artificial diet had lower
      esterase activity than non-Cry1Ac-fed larvae. A resistance mechanism in which
      esterase sequesters Cry1Ac is proposed.

PMID- 15870347
TI  - Suppressive subtractive hybridization of and differences in gene expression
      content of calcifying and noncalcifying cultures of Emiliania huxleyi strain
      1516.
AB  - The marine coccolithophorid Emiliania huxleyi is a cosmopolitan alga intensely
      studied in relation to global carbon cycling, biogeochemistry, marine ecology,
      and biomineralization processes. The biomineralization capabilities of
      coccolithophorids have attracted the attention of scientists interested in
      exploiting this ability for the development of materials science and biomedical
      and biotechnological applications. Although it has been well documented that
      biomineralization in E. huxleyi is promoted by growth under phosphate-limited
      conditions, the genes and proteins that govern the processes of calcification and
      coccolithogenesis remain unknown. Suppressive subtractive hybridization (SSH)
      libraries were constructed from cultures grown in phosphate-limited and phosphate
      replete media as tester and driver populations for reciprocal SSH procedures.
      Positive clones from each of the two libraries were randomly selected, and dot
      blotting was performed for the analysis of expression patterns. A total of 513
      clones from the phosphate-replete library and 423 clones from the phosphate
      limited library were sequenced, assembled, and compared to sequences in GenBank
      using BLASTX. Of the 103 differentially expressed gene fragments from the
      phosphate-replete library, 34% showed significant homology to other known
      proteins, while only 23% of the 65 differentially expressed gene fragments from
      the phosphate-limited library showed homology to other proteins. To further
      assess mRNA expression, real-time RT-PCR analysis was employed and expression
      profiles were generated over a 14-day time course for three clones from the
      phosphate-replete library and five clones from the phosphate-limited library. The
      fragments isolated provide the basis for future cloning of full-length genes and
      functional analysis.

PMID- 15870348
TI  - Quantitative analysis of group II intron expression and splicing in Lactococcus
      lactis.
AB  - The group II intron Ll.ltrB is found within the ltrB relaxase gene of the
      conjugative element pRS01 in Lactococcus lactis. Precise splicing of the intron
      is essential for pRS01 transfer. The transcription regulation and in vivo
      splicing activity of Ll.ltrB have not been investigated thoroughly in L. lactis
      in the natural pRS01 context. We developed absolute quantitative real-time
      reverse transcription-PCR assays to quantify RNA levels of the 5' exon (ltrBE1)
      and the spliced relaxase (ltrB) and intron-encoded protein (ltrA) genes, as well
      as Ll.ltrB splicing activity under different physiological conditions. The mRNA
      levels for the ATP-binding protein OppD were assayed for comparison to the ltrB
      transcripts. The oppD mRNA ranged from 10- to 10,000-fold higher than ltrB region
      genes. ltrBE1 expression was growth-phase dependent. The mRNA level of ltrA was
      almost constant during all growth phases and in all media tested. Ll.ltrB in vivo
      splicing activity ranged from (6.5 +/- 2.1)% to (22.1 +/- 8.0)%. Acid challenge
      significantly decreased both ltrB region mRNA levels and intron splicing
      activity. The presence of recipient cells, different mating environments, and
      temperature stress had no significant effects on expression and splicing. Western
      blotting showed that the level of LtrB protein expressed from an intronless ltrB
      gene was much higher (about 20-fold) than the level of protein expressed from an
      intron-containing construct. Interestingly, LtrB protein showed a tendency to
      function in cis on its oriT target. The low level of ltrB transcript and
      relatively inefficient splicing of the intron may limit Ll.ltrB mobility and
      dissemination in nature.

PMID- 15870349
TI  - Clonal expansion may account for high levels of quinolone resistance in
      Salmonella enterica serovar enteritidis.
AB  - We have observed a high incidence of isolated nalidixic acid resistance in
      Salmonella enterica serovar Enteritidis isolates in Ireland, particularly
      isolates of phage type 1 (PT1). A group of nalidixic acid-resistant (n = 22) and
      nalidixic acid-susceptible (n = 28) isolates of serovar Enteritidis from multiple
      sites in Ireland were selected. Isolates were typed by pulsed-field gel
      electrophoresis (PFGE) with XbaI, and the MICs for nalidixic acid and
      ciprofloxacin were determined. Mutations associated with nalidixic acid
      resistance in clinical isolates and laboratory mutants of serovar Enteritidis and
      32 nalidixic acid-resistant isolates of 15 other salmonella serovars were
      identified. PFGE had limited discriminatory power. A specific point mutation
      (G246T) associated with amino acid substitution Asp87Tyr in the quinolone
      resistance determining region of the gyrA gene accounted for 95% of all mutations
      in serovar Enteritidis and for all mutations in PT1 isolates. Greater diversity
      of mutations was observed among all non-Enteritidis salmonella serovars studied.
      Rates of nalidixic acid resistance in serovar Enteritidis may predominantly
      reflect clonal expansion after infrequent mutation or selection events.

PMID- 15870350
TI  - 13C incorporation into signature fatty acids as an assay for carbon allocation in
      arbuscular mycorrhiza.
AB  - The ubiquitous arbuscular mycorrhizal fungi consume significant amounts of plant
      assimilated C, but this C flow has been difficult to quantify. The neutral lipid
      fatty acid 16:1omega5 is a quantitative signature for most arbuscular mycorrhizal
      fungi in roots and soil. We measured carbon transfer from four plant species to
      the arbuscular mycorrhizal fungus Glomus intraradices by estimating (13)C
      enrichment of 16:1omega5 and compared it with (13)C enrichment of total root and
      mycelial C. Carbon allocation to mycelia was detected within 1 day in monoxenic
      arbuscular mycorrhizal root cultures labeled with [(13)C]glucose. The (13)C
      enrichment of neutral lipid fatty acid 16:1omega5 extracted from roots increased
      from 0.14% 1 day after labeling to 2.2% 7 days after labeling. The colonized
      roots usually were more enriched for (13)C in the arbuscular mycorrhizal fungal
      neutral lipid fatty acid 16:1omega5 than for the root specific neutral lipid
      fatty acid 18:2omega6,9. We labeled plant assimilates by using (13)CO(2) in whole
      plant experiments. The extraradical mycelium often was more enriched for (13)C
      than was the intraradical mycelium, suggesting rapid translocation of carbon to
      and more active growth by the extraradical mycelium. Since there was a good
      correlation between (13)C enrichment in neutral lipid fatty acid 16:1omega5 and
      total (13)C in extraradical mycelia in different systems (r(2) = 0.94), we
      propose that the total amount of labeled C in intraradical and extraradical
      mycelium can be calculated from the (13)C enrichment of 16:1omega5. The method
      described enables evaluation of C flow from plants to arbuscular mycorrhizal
      fungi to be made without extraction, purification and identification of fungal
      mycelia.

PMID- 15870351
TI  - Degradation of azo dyes by laccase and ultrasound treatment.
AB  - The goal of this work was to investigate the decomposition of azo dyes by
      oxidative methods, such as laccase and ultrasound treatments. Each of these
      methods has strong and feeble sides. The laccase treatment showed high
      decolorization rates but cannot degrade all investigated dyes (reactive dyes),
      and high anionic strength led to enzyme deactivation. Ultrasound treatment can
      decolorize all tested dyes after 3 h at a high energy input, and prolonged
      sonication leads to nontoxic ionic species, which was demonstrated by ion
      chromatography and toxicity assays. For the first time, it was shown that a
      combination of laccase and ultrasound treatments can have synergistic effects,
      which was shown by higher degradation rates. Bulk light absorption and ion
      pairing high-performance liquid chromatography (IP-HPLC) were used for process
      monitoring, while with reversed-phase HPLC, a lower number of intermediates than
      expected by IP-HPLC was found. Liquid chromatography-mass spectrometry indicated
      that both acid orange dyes lead to a common end product due to laccase treatment.
      Acid Orange 52 is demethylated by laccase and ultrasound treatment. Further
      results confirmed that the main effect of ultrasound is based on *OH attack on
      the dye molecules.

PMID- 15870352
TI  - Construction of a cloning system for the mass production of a virus-binding
      protein specific for poliovirus type 1.
AB  - In our previous study, virus-binding proteins (VBPs) demonstrating the ability to
      strongly bind poliovirus type 1 (PV1) were recovered from a bacterial culture
      derived from activated sludge. The isolated VBPs would be useful as viral
      adsorbents for water and wastewater treatments. The VBP gene of activated sludge
      bacteria was isolated, and the cloning system of the VBP was established. The
      isolation of the VBP gene from DNA libraries for activated sludge bacteria was
      achieved with the colony hybridization technique. The sequence of the VBP gene
      consisted of 807 nucleotides encoding 268 amino acids. Fifteen amino acid
      sequences were retrieved from 2,137,877 sequences by a homology search using the
      BLAST server at the National Center for Biotechnology Information. The protein
      encoded in the isolated genome was considered to be a newly discovered protein
      from activated sludge culture, because any sequences in protein databases were
      not perfectly matched with the sequence of the VBP. It was confirmed that
      Escherichia coli BL21 transformed by pRSET carrying the isolated VBP gene could
      extensively produce the VBP clones. Enzyme-linked immunosorbent assay (ELISA)
      revealed that the VBP clone exhibited the binding ability with intact particles
      of PV1. The equilibrium binding constant between PV1 and VBP in the ELISA well
      was estimated to be 2.1 x 10(7) (M(-1)), which also indicated that the VBP clones
      have a high affinity with the PV1 particle. The VBP cloning system developed in
      this study would make it possible to produce a mass volume of VBPs and to utilize
      them as a new material of the specific adsorbent in several technologies,
      including virus removal, concentration, and detection.

PMID- 15870353
TI  - Molecular identification and analysis of Borrelia burgdorferi sensu lato in
      lizards in the southeastern United States.
AB  - Lyme borreliosis (LB) group spirochetes, collectively known as Borrelia
      burgdorferi sensu lato, are distributed worldwide. Wild rodents are acknowledged
      as the most important reservoir hosts. Ixodes scapularis is the primary vector of
      B. burgdorferi sensu lato in the eastern United States, and in the southeastern
      United States, the larvae and nymphs mostly parasitize certain species of
      lizards. The primary aim of the present study was to determine whether wild
      lizards in the southeastern United States are naturally infected with Lyme
      borreliae. Blood samples obtained from lizards in Florida and South Carolina were
      tested for the presence of LB spirochetes primarily by using B. burgdorferi sensu
      lato-specific PCR assays that amplify portions of the flagellin (flaB), outer
      surface protein A (ospA), and 66-kDa protein (p66) genes. Attempts to isolate
      spirochetes from a small number of PCR-positive lizards failed. However, PCR
      amplification and sequence analysis of partial flaB, ospA, and p66 gene fragments
      confirmed numerous strains of B. burgdorferi sensu lato, including Borrelia
      andersonii, Borrelia bissettii, and B. burgdorferi sensu stricto, in blood from
      lizards from both states. B. burgdorferi sensu lato DNA was identified in 86 of
      160 (54%) lizards representing nine species and six genera. The high infection
      prevalence and broad distribution of infection among different lizard species at
      different sites and at different times of the year suggest that LB spirochetes
      are established in lizards in the southeastern United States.

PMID- 15870354
TI  - Rapid biosensor for detection of antibiotic-selective growth of Escherichia coli.
AB  - A rapid biosensor for the detection of bacterial growth was developed using
      micromechanical oscillators coated in common nutritive layers. The change in
      resonance frequency as a function of the increasing mass on a cantilever array
      forms the basis of the detection scheme. The calculated mass sensitivity
      according to the mechanical properties of the cantilever sensor is approximately
      50 pg/Hz; this mass corresponds to an approximate sensitivity of approximately
      100 Escherichia coli cells. The sensor is able to detect active growth of E. coli
      cells within 1 h. The starting number of E. coli cells initially attached to the
      sensor cantilever was, on average, approximately 1,000 cells. Furthermore, this
      method allows the detection of selective growth of E. coli within only 2 h by
      adding antibiotics to the nutritive layers. The growth of E. coli was confirmed
      by scanning electron microscopy. This new sensing method for the detection of
      selective bacterial growth allows future applications in, e.g., rapid antibiotic
      susceptibility testing.

PMID- 15870355
TI  - Identification of extracellular N-acylhomoserine lactone acylase from a
      Streptomyces sp. and its application to quorum quenching.
AB  - N-acylhomoserine lactones (AHLs) play an important role in regulating virulence
      factors in pathogenic bacteria. Recently, the enzymatic inactivation of AHLs,
      which can be used as antibacterial targets, has been identified in several soil
      bacteria. In this study, strain M664, identified as a Streptomyces sp., was found
      to secrete an AHL-degrading enzyme into a culture medium. The ahlM gene for AHL
      degradation from Streptomyces sp. strain M664 was cloned, expressed
      heterologously in Streptomyces lividans, and purified. The enzyme was found to be
      a heterodimeric protein with subunits of approximately 60 kDa and 23 kDa. A
      comparison of AhlM with known AHL-acylases, Ralstonia strain XJ12B AiiD and
      Pseudomonas aeruginosa PAO1 PvdQ, revealed 35% and 32% identities in the deduced
      amino acid sequences, respectively. However, AhlM was most similar to the cyclic
      lipopeptide acylase from Streptomyces sp. strain FERM BP-5809, exhibiting 93%
      identity. A mass spectrometry analysis demonstrated that AhlM hydrolyzed the
      amide bond of AHL, releasing homoserine lactone. AhlM exhibited a higher
      deacylation activity toward AHLs with long acyl chains rather than short acyl
      chains. Interestingly, AhlM was also found to be capable of degrading penicillin
      G by deacylation, showing that AhlM has a broad substrate specificity. The
      addition of AhlM to the growth medium reduced the accumulation of AHLs and
      decreased the production of virulence factors, including elastase, total
      protease, and LasA, in P. aeruginosa. Accordingly, these results suggest that AHL
      acylase, AhlM could be effectively applied to the control of AHL-mediated
      pathogenicity.

PMID- 15870356
TI  - Methane-oxidizing bacteria in a California upland grassland soil: diversity and
      response to simulated global change.
AB  - We investigated the diversity of methane-oxidizing bacteria (i.e., methanotrophs)
      in an annual upland grassland in northern California, using comparative sequence
      analysis of the pmoA gene. In addition to identifying type II methanotrophs
      commonly found in soils, we discovered three novel pmoA lineages for which no
      cultivated members have been previously reported. These novel pmoA clades
      clustered together either with clone sequences related to "RA 14" or "WB5FH-A,"
      which both represent clusters of environmentally retrieved sequences of putative
      atmospheric methane oxidizers. Conservation of amino acid residues and rates of
      nonsynonymous versus synonymous nucleotide substitution in these novel lineages
      suggests that the pmoA genes in these clades code for functionally active methane
      monooxygenases. The novel clades responded to simulated global changes
      differently than the type II methanotrophs. We observed that the relative
      abundance of type II methanotrophs declined in response to increased
      precipitation and increased atmospheric temperature, with a significant
      antagonistic interaction between these factors such that the effect of both
      together was less than that expected from their individual effects. Two of the
      novel clades were not observed to respond significantly to these environmental
      changes, while one of the novel clades had an opposite response, increasing in
      relative abundance in response to increased precipitation and atmospheric
      temperature, with a significant antagonistic interaction between these factors.

PMID- 15870357
TI  - Production of autoinducer 2 in Salmonella enterica serovar Thompson contributes
      to its fitness in chickens but not on cilantro leaf surfaces.
AB  - Food-borne illness caused by Salmonella enterica has been linked traditionally to
      poultry products but is associated increasingly with fresh fruits and vegetables.
      We have investigated the role of the production of autoinducer 2 (AI-2) in the
      ability of S. enterica serovar Thompson to colonize the chicken intestine and the
      cilantro phyllosphere. A mutant of S. enterica serovar Thompson that is defective
      in AI-2 production was constructed by insertional mutagenesis of luxS. The
      population size of the S. enterica serovar Thompson parental strain was
      significantly higher than that of its LuxS(-) mutant in the intestine, spleen,
      and droppings of chicks 12 days after their oral inoculation with the strains in
      a ratio of 1:1. In contrast, no significant difference in the population dynamics
      of the parental and LuxS(-) strain was observed after their inoculation singly or
      in mixtures onto cilantro plants. Digital image analysis revealed that 54% of S.
      enterica serovar Thompson cells were present in large aggregates on cilantro
      leaves but that the frequency distributions of the size of aggregates formed by
      the parental strain and the LuxS(-) mutant were not significantly different.
      Carbon utilization profiles indicated that the AI-2-producing strain utilized a
      variety of amino and organic acids more efficiently than its LuxS(-) mutant but
      that most sugars were utilized similarly in both strains. Thus, inherent
      differences in the nutrients available to S. enterica in the phyllosphere and in
      the chicken intestine may underlie the differential contribution of AI-2
      synthesis to the fitness of S. enterica in these environments.

PMID- 15870358
TI  - Differential gene expression profiling of Staphylococcus aureus cultivated under
      biofilm and planktonic conditions.
AB  - It is well known that biofilm formation by pathogenic staphylococci on implanted
      medical devices leads to "chronic polymer-associated infections." Bacteria in
      these biofilms are more resistant to antibiotics and the immune defense system
      than their planktonic counterparts, which suggests that the cells in a biofilm
      have altered metabolic activity. To determine which genes are up-regulated in
      Staphylococcus aureus biofilm cells, we carried out a comparative transcriptome
      analysis. Biofilm growth was simulated on dialysis membranes laid on agar plates.
      Staphylococci were cultivated planktonically in Erlenmeyer flasks with shaking.
      mRNA was isolated at five time points from cells grown under both conditions and
      used for hybridization with DNA microarrays. The gene expression patterns of
      several gene groups differed under the two growth conditions. In biofilm cells,
      the cell envelope appeared to be a very active compartment since genes encoding
      binding proteins, proteins involved in the synthesis of murein and
      glucosaminoglycan polysaccharide intercellular adhesin, and other enzymes
      involved in cell envelope synthesis and function were significantly up-regulated.
      In addition, evidence was obtained that formate fermentation, urease activity,
      the response to oxidative stress, and, as a consequence thereof, acid and
      ammonium production are up-regulated in a biofilm. These factors might contribute
      to survival, persistence, and growth in a biofilm environment. Interestingly,
      toxins and proteases were up-regulated under planktonic growth conditions.
      Physiological and biochemical tests for the up-regulation of urease, formate
      dehydrogenase, proteases, and the synthesis of staphyloxanthin confirmed the
      microarray data.

PMID- 15870359
TI  - Architecture of a nascent Sphingomonas sp. biofilm under varied hydrodynamic
      conditions.
AB  - The architecture of a Sphingomonas biofilm was studied during early phases of its
      formation, using strain L138, a gfp-tagged derivative of Sphingomonas sp. strain
      LB126, as a model organism and flow cells and confocal laser scanning microscopy
      as experimental tools. Spatial and temporal distribution of cells and exopolymer
      secretions (EPS) within the biofilm, development of microcolonies under flow
      conditions representing varied Reynolds numbers, and changes in diffusion length
      with reference to EPS production were studied by sequential sacrificing of
      biofilms grown in multichannel flow cells and by time-lapse confocal imaging. The
      area of biofilm in terms of microscopic images required to ensure representative
      sampling varied by an order of magnitude when area of cell coverage (2 x 10(5)
      microm(2)) or microcolony size (1 x 10(6) microm(2)) was the biofilm parameter
      under investigation. Hence, it is necessary to establish the inherent variability
      of any biofilm metric one is attempting to quantify. Sphingomonas sp. strain L138
      biofilm architecture consisted of microcolonies and extensive water channels.
      Biomass and EPS distribution were maximal at 8 to 9 mum above the substratum,
      with a high void fraction near the substratum. Time-lapse confocal imaging and
      digital image analysis showed that growth of the microcolonies was not uniform:
      adjacently located colonies registered significant growth or no growth at all.
      Microcolonies in the biofilm had the ability to move across the attachment
      surface as a unit, irrespective of fluid flow direction, indicating that movement
      of microcolonies is an inherent property of the biofilm. Width of water channels
      decreased as EPS production increased, resulting in increased diffusion distances
      in the biofilm. Changing hydrodynamic conditions (Reynolds numbers of 0.07, 52,
      and 87) had no discernible influence on the characteristics of microcolonies
      (size, shape, or orientation with respect to flow) during the first 24 h of
      biofilm development. Inherent factors appear to have overriding influence, vis-a
      vis environmental factors, on early stages of microcolony development under these
      laminar flow conditions.

PMID- 15870360
TI  - Polychlorinated biphenyl rhizoremediation by Pseudomonas fluorescens F113
      derivatives, using a Sinorhizobium meliloti nod system to drive bph gene
      expression.
AB  - Rhizoremediation of organic chemicals requires high-level expression of
      biodegradation genes in bacterial strains that are excellent rhizosphere
      colonizers. Pseudomonas fluorescens F113 is a biocontrol strain that was shown to
      be an excellent colonizer of numerous plant rhizospheres, including alfalfa.
      Although a derivative of F113 expressing polychlorinated biphenyl (PCB)
      biodegradation genes (F113pcb) has been reported previously, this strain shows a
      low level of bph gene expression, limiting its rhizoremediation potential. Here,
      a high-level expression system was designed from rhizobial nod gene regulatory
      relays. Nod promoters were tested in strain F113 by using beta-galactosidase
      transcriptional fusions. This analysis showed that nodbox 4 from Sinorhizobium
      meliloti has a high level of expression in F113 that is dependent on an intact
      nodD1 gene. A transcriptional fusion of a nodbox cassette containing the nodD1
      gene and nodbox 4 fused to a gfp gene was expressed in the alfalfa rhizosphere.
      The bph operon from Burkholderia sp. strain LB400 was cloned under the control of
      the nodbox cassette and was inserted as a single copy into the genome of F113,
      generating strain F113L::1180. This new genetically modified strain has a high
      level of BphC activity and grows on biphenyl as a sole carbon and energy source
      at a growth rate that is more than three times higher than that of F113pcb.
      Degradation of PCBs 3, 4, 5, 17, and 25 was also much faster in F113L::1180 than
      in F113pcb. Finally, the modified strain cometabolized PCB congeners present in
      Delor103 better than strain LB400, the donor of the bph genes used.

PMID- 15870361
TI  - Distribution and stability of sulfate-reducing prokaryotic and hydrogenotrophic
      methanogenic assemblages in nutrient-impacted regions of the Florida Everglades.
AB  - Although the influence of phosphorus loading on the Everglades ecosystem has
      received a great deal of attention, most research has targeted macro indicators,
      such as those based on vegetation or fauna, or chemical and physical parameters
      involved in biogeochemical cycles. Fewer studies have addressed the role of
      microorganisms, and these have mainly targeted gross informative parameters such
      as microbial biomass, enzymatic activities, and microbial enumerations. The
      objectives of this study were to characterize the dynamics of sulfate-reducing
      and methanogenic assemblages using terminal restriction fragment length
      polymorphism (T-RFLP) targeting the dissimilatory sulfite reductase (dsrA) and
      methyl coenzyme M reductase (mcrA) genes, respectively, and assess the impact of
      nutrient enrichment on microbial assemblages in the northern Everglades. T-RFLP
      combined with principal component analysis was a powerful technique to
      discriminate between soils from sites with eutrophic, transitional, and
      oligotrophic nutrient concentrations. dsrA T-RFLP provided a higher level of
      discrimination between the three sites. mcrA was a relatively weaker system to
      distinguish between sites, since it could not categorically discriminate between
      eutrophic and transition soil samples, but may be useful as an early indicator of
      phosphorus loading which is altering hydrogenotrophic methanogenic community in
      the transition zones, making them more similar to eutrophic zones. Clearly,
      targeting a combination of different microbial communities provides greater
      insight into the functioning of this ecosystem and provides useful information
      for understanding the relationship between eutrophication effects and microbial
      assemblages.

PMID- 15870362
TI  - Use of a quartz crystal microbalance to investigate the antiadhesive potential of
      N-acetyl-L-cysteine.
AB  - The reduction of bacterial biofilm formation on stainless steel surfaces by N
      acetyl-L-cysteine (NAC) is attributed to effects on bacterial growth and
      polysaccharide production, as well as an increase in the wettability of steel
      surfaces. In this report, we show that NAC-coated stainless steel and polystyrene
      surfaces affect both the initial adhesion of Bacillus cereus and Bacillus
      subtilis and the viscoelastic properties of the interaction between the adhered
      bacteria and the surface. A quartz crystal microbalance with dissipation was
      shown to be a powerful and sensitive technique for investigating changes in the
      applied NAC coating for initial cell surface interactions of bacteria. The
      kinetics of frequency and dissipation shifts were dependent on the bacteria, the
      life cycle stage of the bacteria, and the surface. We found that exponentially
      grown cells gave rise to a positive frequency shift as long as their cell surface
      hydrophobicity was zero. Furthermore, when the characteristics of binding between
      the cell and the surface for different growth phases were compared, the rigidity
      increased from exponentially grown cells to starved cells. There was a trend in
      which an increase in the viscoelastic properties of the interaction, caused by
      the NAC coating on stainless steel, resulted in a reduction in irreversibly
      adhered cells. Interestingly, for B. cereus that adhered to polystyrene, the
      viscoelastic properties decreased, while there was a reduction in adhered cells,
      regardless of the life cycle stage. Altogether, NAC coating on surfaces was often
      effective and could both decrease the initial adhesion and increase the
      detachment of adhered cells and spores. The most effective reduction was found
      for B. cereus spores, for which the decrease was caused by a combination of these
      two parameters.

PMID- 15870363
TI  - Changes in nitrogen-fixing and ammonia-oxidizing bacterial communities in soil of
      a mixed conifer forest after wildfire.
AB  - This study was undertaken to examine the effects of forest fire on two important
      groups of N-cycling bacteria in soil, the nitrogen-fixing and ammonia-oxidizing
      bacteria. Sequence and terminal restriction fragment length polymorphism (T-RFLP)
      analysis of nifH and amoA PCR amplicons was performed on DNA samples from
      unburned, moderately burned, and severely burned soils of a mixed conifer forest.
      PCR results indicated that the soil biomass and proportion of nitrogen-fixing and
      ammonia-oxidizing species was less in soil from the fire-impacted sites than from
      the unburned sites. The number of dominant nifH sequence types was greater in
      fire-impacted soils, and nifH sequences that were most closely related to those
      from the spore-forming taxa Clostridium and Paenibacillus were more abundant in
      the burned soils. In T-RFLP patterns of the ammonia-oxidizing community, terminal
      restriction fragments (TRFs) representing amoA cluster 1, 2, or 4 Nitrosospira
      spp. were dominant (80 to 90%) in unburned soils, while TRFs representing amoA
      cluster 3A Nitrosospira spp. dominated (65 to 95%) in fire-impacted soils. The
      dominance of amoA cluster 3A Nitrosospira spp. sequence types was positively
      correlated with soil pH (5.6 to 7.5) and NH(3)-N levels (0.002 to 0.976 ppm),
      both of which were higher in burned soils. The decreased microbial biomass and
      shift in nitrogen-fixing and ammonia-oxidizing communities were still evident in
      fire-impacted soils collected 14 months after the fire.

PMID- 15870364
TI  - Combined approach for characterization of uncultivated magnetotactic bacteria
      from various aquatic environments.
AB  - Both magnetic collection and "race track" purification techniques were highly
      effective for selective enrichment of magnetotactic bacteria (MTB) from complex
      communities, as suggested by amplified ribosomal DNA restriction analysis and
      denaturing gradient gel electrophoresis combined with sequence analysis of 16S
      rRNA genes. Using these purification methods, the occurrence and diversity of MTB
      in microcosms from various marine and freshwater environments were assayed by
      using a combined microscopic, molecular, and cultivation approach. Most
      microcosms were dominated by magnetotactic cocci. Consistently, the majority of
      retrieved 16S RNA sequences were affiliated with a distinct cluster in the
      Alphaproteobacteria. Within this lineage the levels of sequence divergence were
      <1 to 11%, indicating genus-level diversity between magnetotactic cocci from
      various microcosms, as well as between MTB from different stages of succession of
      the same microcosms. The community composition in microscosms underwent drastic
      succession during incubation, and significant heterogeneities were observed
      between microcosms from the same environmental sources. A novel magnetotactic rod
      (MHB-1) was detected in a sediment sample from a lake in northern Germany by
      fluorescence in situ hybridization. MHB-1 falls into the Nitrospira phylum,
      displaying 91% 16S rRNA sequence similarity to "Magnetobacterium bavaricum." In
      extensive cultivation attempts, we failed to isolate MHB-1, as well as most other
      MTB present in our samples. However, although magnetotactic spirilla were not
      frequently observed in the enrichments, 10 novel isolates of the genus
      Magnetospirillum which had not routinely been isolated in pure culture before
      were obtained.

PMID- 15870365
TI  - Sensitivity of planktonic and biofilm-associated Salmonella spp. to ionizing
      radiation.
AB  - Salmonella enterica forms biofilms that are relatively resistant to chemical
      sanitizing treatments. Ionizing radiation has been used to inactivate Salmonella
      on a variety of foods and contact surfaces, but the relative efficacy of the
      process against biofilm-associated cells versus free-living planktonic cells is
      not well documented. The radiation sensitivity of planktonic or biofilm
      associated cells was determined for three food-borne-illness-associated isolates
      of Salmonella. Biofilms were formed on sterile glass slides in a coincubation
      apparatus, using inoculated tryptic soy broth, incubated at 37 degrees C for 48
      h. Resulting biofilms were 18 to 24 microm in height as determined by confocal
      scanning laser microscopy. The planktonic and biofilm cultures were gamma
      irradiated to doses of 0.0 (control), 0.5, 1.0, 1.5, 2.0 and 2.5 kGy. The D(10)
      value (the dose of radiation required to reduce a population by 1 log(10), or
      90%) was calculated for each isolate-culture based on surviving populations at
      each radiation dose. The D(10) values of S. enterica serovar Anatum were not
      significantly (P < 0.05) different for biofilm-associated (0.645 kGy) and
      planktonic (0.677 kGy) cells. In contrast, the biofilm-associated cells of S.
      enterica serovar Stanley were significantly more sensitive to ionizing radiation
      than the respective planktonic cells, with D(10) values of 0.531 and 0.591 kGy,
      respectively. D(10) values of S. enterica serovar Enteritidis were similarly
      reduced for biofilm-associated (0.436 kGy) versus planktonic (0.535 kGy) cells.
      The antimicrobial efficacy of ionizing radiation is therefore preserved or
      enhanced in treatment of biofilm-associated bacteria.

PMID- 15870366
TI  - Transcriptome analysis of recombinant protein secretion by Aspergillus nidulans
      and the unfolded-protein response in vivo.
AB  - Filamentous fungi have a high capacity for producing large amounts of secreted
      proteins, a property that has been exploited for commercial production of
      recombinant proteins. However, the secretory pathway, which is key to the
      production of extracellular proteins, is rather poorly characterized in
      filamentous fungi compared to yeast. We report the effects of recombinant protein
      secretion on gene expression levels in Aspergillus nidulans by directly comparing
      a bovine chymosin-producing strain with its parental wild-type strain in
      continuous culture by using expressed sequence tag microarrays. This approach
      demonstrated more subtle and specific changes in gene expression than those
      observed when mimicking the effects of protein overproduction by using a
      secretion blocker. The impact of overexpressing a secreted recombinant protein
      more closely resembles the unfolded-protein response in vivo.

PMID- 15870367
TI  - Enumeration of respiring Pseudomonas spp. in milk within 6 hours by fluorescence
      in situ hybridization following formazan reduction.
AB  - Respiring Pseudomonas spp. in milk were quantified within 6 h by fluorescence in
      situ hybridization (FISH) with vital staining. FISH with an oligonucleotide probe
      based on 16S rRNA sequences was used for the specific detection of Pseudomonas
      spp. at the single cell level. 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) was
      used to estimate bacterial respiratory activity. The numbers of respiring
      Pseudomonas cells as determined by FISH with CTC staining (CTC-FISH) were almost
      the same or higher than the numbers of CFU as determined by the conventional
      culture method.

PMID- 15870368
TI  - Dose determination for acute Salmonella infection in pigs.
AB  - Pigs were exposed to various levels of Salmonella enterica subsp. enterica
      serovar Typhimurium by either intranasal inoculation or by subjecting them to a
      contaminated environment. More than 10(3) salmonellae were required to induce
      acute Salmonella infection. These results indicate that intervention against
      acute Salmonella infection in lairage may be more readily achieved than
      previously thought.

PMID- 15870369
TI  - Persistence of Enterococcus faecalis in aquatic environments via surface
      interactions with copepods.
AB  - Several human pathogens and fecal-pollution indicators may persist as viable
      organisms in natural environments, owing to their ability to activate different
      types of survival strategies. These strategies include adhesion on both abiotic
      and biotic surfaces and the entrance to the so-called viable but nonculturable
      (VBNC) state. In an 18-month survey for the detection of enterococci in both lake
      water and seawater, C. Signoretto et al. (Appl. Environ. Microbiol. 70:6892-6896,
      2004) have shown that Enterococcus faecalis was detected mostly bound to plankton
      and in the VBNC state. In the present study, we show that in vitro adhesion of E.
      faecalis to copepods accelerated the entry of cells into the VBNC state relative
      to that of planktonic bacteria. VBNC E. faecalis cells maintained their adhesive
      properties to copepods and chitin (the main component of the copepod carapace),
      though to a reduced extent in comparison with growing cells. Sugar competition
      experiments showed interference with adhesion to both copepods and chitin by
      GlcNAc and only to copepods by D-mannose. Four enterococcal cell wall proteins
      present in both growing and VBNC cells and lipoteichoic acid were shown to be
      capable of binding chitin. The results indicate that copepods may represent an
      additional environmental reservoir of enterococci, thus suggesting the
      advisability of redesigning the protocols currently used for microbial detection
      during the evaluation of the microbiological quality of environmental samples.

PMID- 15870370
TI  - The gene yggE functions in restoring physiological defects of Escherichia coli
      cultivated under oxidative stress conditions.
AB  - DNA microarray analysis showed that yfiD, yggB, and yggE genes were up-regulated
      when superoxide dismutase (SOD)-deficient Escherichia coli IM303 (I4) was
      cultivated under the oxidative stress generated by photoexcited TiO(2), and pYFD,
      pYGB, and pYGE were constructed by inserting the respective genes into a pUC 19
      vector. The content of reactive oxygen species (ROS) in IM303 (I4) cells carrying
      pYGE was reduced to 31% of ROS content in the control cells with pUC 19. In the
      culture of wild-type strain, E. coli MM294, in the medium with paraquat (10
      micromol/l), maximum specific growth rate of the cells with pYGE was about five
      times higher than that of the control cells, with a decreased ROS content in the
      former cells. The introduction of pYGE also suppressed the occurrence of the
      cells with altered amino acid requirement in the culture of MM294 cells with
      paraquat.

PMID- 15870371
TI  - Molecular analysis of human, porcine, and poultry Enterococcus faecium isolates
      and their erm(B) genes.
AB  - Fifty-nine erm(B)-positive Enterococcus faecium strains isolated from pigs,
      broilers, and humans were typed using multilocus sequence typing (MLST), and the
      coding sequence of the erm(B) gene was determined. Identical erm(B) gene
      sequences were detected in genetically unrelated isolates. Furthermore,
      genetically indistinguishable strains were found to contain different erm(B)
      alleles. This may suggest that horizontal exchange of the erm(B) gene between
      animal and human E. faecium strains or the existence of a common reservoir of
      erm(B) genes might be more important than direct transmission of resistant
      strains.

PMID- 15870372
TI  - Investigation of the microbial ecology of intertidal hot springs by using
      diversity analysis of 16S rRNA and chitinase genes.
AB  - The microbial diversity of intertidal hot springs on the seashore of northwest
      Iceland was examined by combining directed in situ enrichments, artificial
      support colonization, and mat sampling. Analysis of 16S rRNA genes revealed the
      presence of clones related to both marine and terrestrial, thermophilic,
      mesophilic, and psychrophilic microorganisms scattered among 11 bacterial
      divisions. No archaea were found. The species composition of the enrichments was
      affected by the length of the hot periods experienced at low tide and was very
      different from those found in the biomass. A total of 36 chitinase genes were
      detected by molecular screening of the samples with degenerate primers for
      glycoside hydrolase family 18. The chitinase gene diversity was at least twofold
      higher in the enrichment samples than in the controls, indicating that a much
      higher diversity of hydrolytic genes can be accessed with this approach.

PMID- 15870373
TI  - Homologous and heterologous overexpression in Clostridium acetobutylicum and
      characterization of purified clostridial and algal Fe-only hydrogenases with high
      specific activities.
AB  - Clostridium acetobutylicum ATCC 824 was selected for the homologous
      overexpression of its Fe-only hydrogenase and for the heterologous expressions of
      the Chlamydomonas reinhardtii and Scenedesmus obliquus HydA1 Fe-only
      hydrogenases. The three Strep tag II-tagged Fe-only hydrogenases were isolated
      with high specific activities by two-step column chromatography. The purified
      algal hydrogenases evolve hydrogen with rates of around 700 micromol H(2) min(-1)
      mg(-1), while HydA from C. acetobutylicum (HydA(Ca)) shows the highest activity
      (5,522 micromol H(2) min(-1) mg(-1)) in the direction of hydrogen uptake.
      Further, kinetic parameters and substrate specificity were reported. An electron
      paramagnetic resonance (EPR) analysis of the thionin-oxidized HydA(Ca) protein
      indicates a characteristic rhombic EPR signal that is typical for the oxidized H
      cluster of Fe-only hydrogenases.

PMID- 15870374
TI  - Lactococcus lactis SpOx spontaneous mutants: a family of oxidative-stress
      resistant dairy strains.
AB  - Numerous industrial bacteria generate hydrogen peroxide (H(2)O(2)), which may
      inhibit the growth of other bacteria in mixed ecosystems. We isolated spontaneous
      oxidative-stress-resistant (SpOx) Lactococcus lactis mutants by using a natural
      selection method with milk-adapted strains on dairy culture medium containing
      H(2)O(2). Three SpOx mutants displayed greater H(2)O(2) resistance. One of them,
      SpOx3, demonstrated better behavior in different oxidative-stress situations: (i)
      higher long-term survival upon aeration in LM17 and milk and (ii) the ability to
      grow with H(2)O(2)-producing Lactobacillus delbrueckii subsp. delbrueckii
      strains. Furthermore, the transit kinetics of the SpOx3 mutant in the digestive
      tract of a human flora-associated mouse model was not affected.

PMID- 15870375
TI  - Genetically engineered wine yeast produces a high concentration of L-lactic acid
      of extremely high optical purity.
AB  - For mass production of lactic acid, we newly constructed a transgenic wine yeast
      strain that included six copies of the bovine L-lactate dehydrogenase gene on the
      genome. On fermentation in inexpensive cane juice-based medium, L-lactate
      production of this recombinant reached 122 g/liter and the optical purity was
      99.9% or higher.

PMID- 15870376
TI  - Mass outbreak of food poisoning disease caused by small amounts of staphylococcal
      enterotoxins A and H.
AB  - It was believed that food poisoning in Osaka in 2000 was due to small amounts of
      staphylococcal enterotoxin A (SEA) in reconstituted milk. Results of this study
      clearly indicate that SEH was also present in the raw material of reconstituted
      milk, indicating that the food poisoning was caused by multiple staphylococcal
      enterotoxins.

PMID- 15870377
TI  - Combined antimicrobial resistance in Enterococcus faecium isolated from chickens.
AB  - Nineteen E. faecium strains isolated from chicken caecum samples, collected in
      slaughterhouses and highly resistant to vancomycin or gentamicin, were
      coresistant to erythromycin, and/or tetracyclines, and/or streptogramins, and/or
      avilamycin. Multiple antibiotic resistance was related to the presence in various
      combinations of aac(6')-aph(2"), erm(B), emtA, mef(A), tet(L), tet(M), and vanA
      genes.

PMID- 15870378
TI  - UV inactivation of Cryptosporidium hominis as measured in cell culture.
AB  - The Cryptosporidium spp. UV disinfection studies conducted to date have used
      Cryptosporidium parvum oocysts. However, Cryptosporidium hominis predominates in
      human cryptosporidiosis infections, so there is a critical need to assess the
      efficacy of UV disinfection of C. hominis. This study utilized cell culture-based
      methods to demonstrate that C. hominis oocysts displayed similar levels of
      infectivity and had the same sensitivity to UV light as C. parvum. Therefore, the
      water industry can be confident about extrapolating C. parvum UV disinfection
      data to C. hominis oocysts.

PMID- 15870379
TI  - Role of cytochrome B5 in modulating peroxide-supported cyp3a4 activity: evidence
      for a conformational transition and cytochrome P450 heterogeneity.
AB  - The role of cytochrome b(5) (b(5)) in the alpha-naphthoflavone (alpha-NF)
      mediated inhibition of H(2)O(2)-supported 7-benzyloxyquinoline (7-BQ)
      debenzylation by heterologously expressed and purified cytochrome P450 3A4
      (CYP3A4) was studied. Although alpha-NF showed negligible effect in an NADPH
      dependent reconstituted system, inhibition of 7-BQ oxidation was observed in the
      H(2)O(2) system. Analysis of the effect of various constituents of a standard
      reconstituted system on H(2)O(2)-supported activity showed that b(5) alone
      resulted in a 2.5-fold increase in the k(cat) value and reversed the inhibitory
      effect of alpha-NF. In addition, titration with b(5) suggested that only 65% of
      the CYP3A4 participated in the interaction with b(5), consistent with cytochrome
      P450 (P450) heterogeneity. Study of the influence of b(5) on the kinetics of
      H(2)O(2)-dependent destruction of the P450 heme moiety suggested two distinct
      conformers of CYP3A4 with different sensitivity to heme loss. In the absence of
      b(5), 66% of the wild-type enzyme was bleached in the fast phase, whereas the
      addition of b(5) decreased the fraction of the fast phase to 16%. Finally, to
      locate amino acid residues that might influence b(5) action, several active site
      mutants were tested. Substitution of Ser-119, Ile-301, Ala-305, Ile-369, or Ala
      370 with the larger Phe or Trp decreased or even abolished the activation by
      b(5). Ser-119 is in the B'-C loop, a predicted b(5)-P450 interaction site, and
      Ile-301 and Ala-305 are closest to the heme. In conclusion, the interaction of
      b(5) with P450 apparently leads to a conformational transition, which results in
      redistribution of the CYP3A4 pool.

PMID- 15870380
TI  - The dietary polyphenol ellagic acid is a potent inhibitor of hOAT1.
AB  - Ellagic acid (EA), a polyphenol present in berries, has been demonstrated to be
      preventive of esophageal and colon cancer in animals. Here, we have studied the
      ability of organic anion transporters (OATs) and organic anion-transporting
      polypeptides (OATPs) to transport EA. The accumulation of radiolabeled (14)C]EA,
      [(3)H]p-aminohippuric acid (PAH), [(14)C]glutarate, [(3)H]estrone sulfate,
      [(3)H]ochratoxin A, and [(3)H]taurocholic acid +/- inhibitor(s) was tested in OAT
      and OATP-expressing oocytes. Oocytes expressing human (h)OAT1, rat (r)Oat1, and
      hOAT4 accumulated 6.5-, 7.1-, and 8.9-fold more EA, respectively, than did water
      injected oocytes. This accumulation was prevented by the prototype OAT inhibitors
      bromosulfophthalein and probenecid. rOatp1, mouse (m)Oat2, hOAT3, and mOat5
      showed no EA transport. The uptake of the prototype OAT substrate PAH in hOAT1
      expressing oocytes was dose dependently and potently inhibited by EA with an
      IC(50)of 207 nM. In conclusion, we have demonstrated that the OAT family members
      hOAT1, rOat1, and hOAT4 mediate transport of EA, with a very high affinity for
      hOAT1.

PMID- 15870381
TI  - AT1 receptor-mediated enhancement of collecting duct renin in angiotensin II
      dependent hypertensive rats.
AB  - Angiotensin II (ANG II)-infused rats exhibit increases in distal nephron renin
      expressed in principal cells of connecting tubules and collecting ducts. This
      study was performed to determine whether the augmentation of distal nephron renin
      involves ANG II type 1 (AT1) receptor activation. Male Sprague-Dawley rats (200
      220 g) were divided into three groups: 1) sham operated (n = 8); 2) ANG II
      infused (80 ng/min, 13 days, n = 8); and 3) ANG II infused plus AT1 receptor
      blocker (ARB), olmesartan (5 mg/days, n = 8). ANG II infusion increased systolic
      blood pressure (BP; 178 +/- 4 vs. 122 +/- 1 mmHg; P < 0.001) and suppressed
      plasma renin activity (PRA; 0.08 +/- 0.1 vs. 5.3 +/- 0.8 ng ANG I x ml(-1) x h(
      1)). ARB treatment prevented the increase in BP (113 +/- 6 mmHg) and led to
      increases in PRA (15.8 +/- 1.5 ng ANG I x ml(-1) x h(-1)). Renin protein levels
      measured in the kidney medulla, to avoid contribution from juxtaglomerular
      apparatus cells, were higher in ANG II-infused rats [1.64 +/- 0.3 vs. 1.00 +/-
      0.1 densitometric units (DU) compared with sham-operated rats; P < 0.05], and ARB
      treatment prevented this increase (1.01 +/- 0.1). Similarly, renin
      immunoreactivity increased in medullary collecting ducts of ANG II-infused
      compared with sham-operated rats (2.5 +/- 0.3 vs. 1.0 +/- 0.2 DU; P < 0.001),
      which was also prevented by ARB (1.01 +/- 0.06). Renin qRTPCR in ANG II-infused
      rats showed higher mRNA levels in the kidney medulla compared with sham-operated
      rats (5.5 +/- 2.3 vs. 0.04 +/- 0.02 ratio to GAPDH mRNA levels; P < 0.001);
      however, renin transcript levels were normalized in the ARB-treated rats. These
      data demonstrate that the augmentation of distal nephron renin in ANG II-infused
      hypertensive rats is AT1 receptor mediated. The augmented distal tubular renin
      may contribute to increased intratubular ANG II levels and distal nephron sodium
      reabsorption in ANG II-dependent hypertension.

PMID- 15870382
TI  - Development of age-dependent glomerular lesions in galectin-3/AGE-receptor-3
      knockout mice.
AB  - Aging is characterized by renal functional and structural abnormalities
      resembling those observed in diabetes. These changes have been related to the
      progressive accumulation of advanced glycation end-products (AGEs) and cumulative
      oxidative stress occurring in both conditions. We previously reported that
      galectin-3 ablation is associated with increased susceptibility to diabetes- and
      AGE-induced glomerulopathy, thus indicating a protective role of galectin-3 as an
      AGE receptor. To investigate the role of the AGE/AGE receptor pathway in the
      pathogenesis of age-related renal disease, we evaluated the development of
      glomerular lesions in aging galectin-3 knockout (KO) vs. wild-type (WT) mice and
      their relation to the increased AGE levels and oxidative stress characterizing
      the aging process. KO mice showed significantly more pronounced age-dependent
      increases in proteinuria, albuminuria, glomerular sclerosis, and glomerular and
      mesangial areas, starting at 18 mo, as well as renal extracellular matrix mRNA
      and protein expression, starting at 12 mo vs. age-matched WT mice. Circulating
      and renal AGEs, plasma isoprostane 8-epi-PGF2alpha levels, glomerular content of
      the glycoxidation and lipoxidation products N(epsilon)-carboxymethyllysine and 4
      hydroxy-2-nonenal, and renal nuclear factor-kappaB activity also increased more
      markedly with age in KO than WT mice. AGE levels correlated significantly with
      renal functional and structural parameters. These data indicate that aging
      galectin-3 KO mice develop more pronounced changes in renal function and
      structure than coeval WT mice, in parallel with a more marked degree of AGE
      accumulation, oxidative stress, and associated low-grade inflammation, thus
      supporting the concept that the AGE/AGE receptor pathway is implicated in age
      related renal disease.

PMID- 15870383
TI  - Expression of polycystin-1 enhances endoplasmic reticulum calcium uptake and
      decreases capacitative calcium entry in ATP-stimulated MDCK cells.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) types 1 and 2 arise as a
      consequence of mutations in the PKD1 or PKD2 genes, encoding polycystins-1 and 
      2. Because loss of function of either of the polycystins leads to a very similar
      phenotype and the two proteins are known to interact, polycystins-1 and -2 are
      probably active in the same pathway. The way in which loss of either polycystin
      leads to the development of ADPKD remains to be established, but disturbances of
      cell calcium regulation are likely to play an important role. Here, we
      demonstrate that polycystin-1, heterologously expressed in Madin-Darby canine
      kidney cells, had a pronounced effect on intracellular calcium homeostasis. ATP
      induced calcium responses in transfection control cells exhibited a double peak
      and relatively gradual return to baseline. By contrast, cells expressing
      heterologous polycystin-1 showed a brief, uniphasic peak and an accelerated rate
      of decay. Heterologously expressed polycystin-1 accelerated endoplasmic reticulum
      (ER) calcium reuptake and inhibited capacitative calcium entry; we found no
      effect of the protein on mitochondrial calcium buffering or plasma membrane
      calcium extrusion. We therefore propose that polycystin-1 accelerated the decay
      of the cell calcium response to ATP by upregulation of ER calcium reuptake and
      consequent minimization of the stimulus for capacitative calcium entry. It is
      possible that cellular dedifferentiation, fluid secretion, and proliferation
      might therefore arise in ADPKD as a consequence of disturbances in cytoplasmic
      and ER calcium homeostasis and aberrant capacitative calcium entry.

PMID- 15870384
TI  - Mutually dependent localization of megalin and Dab2 in the renal proximal tubule.
AB  - Disabled-2 (Dab2) is a cytoplasmic adaptor protein that binds to the cytoplasmic
      tail of the multiligand endocytic receptor megalin, abundantly expressed in renal
      proximal tubules. Deletion of Dab2 induces a urinary increase in specific plasma
      proteins such as vitamin D binding protein and retinol binding protein (Morris
      SM, Tallquist MD, Rock CO, and Cooper JA. EMBO J 21: 1555-1564, 2002). However,
      the subcellular localization of Dab2 in the renal proximal tubule and its
      function have not been fully elucidated yet. Here, we report the characterization
      of Dab2 in the renal proximal tubule. Immunohistocytochemistry revealed
      colocalization with megalin in coated pits and vesicles but not in dense apical
      tubules and the brush border. Kidney-specific megalin knockout almost abolished
      Dab2 staining, indicating that Dab2 subcellular localization requires megalin in
      the proximal tubule. Reciprocally, knockout of Dab2 led to a redistribution of
      megalin from endosomes to microvilli. In addition, there was an overall decrease
      in levels of megalin protein observed by immunoblotting but no decrease in
      clathrin or alpha-adaptin protein levels or in megalin mRNA. In rat yolk sac
      epithelial BN16 cells, Dab2 was present apically and colocalized with megalin.
      Introduction of anti-Dab2 antibody into BN16 cells decreased the internalization
      of 125I-labeled receptor-associated protein, substantiating the role of Dab2 in
      megalin-mediated endocytosis. The present study shows that Dab2 is localized in
      the apical endocytic apparatus of the renal proximal tubule and that this
      localization requires megalin. Furthermore, the study suggests that the urinary
      loss of megalin ligands observed in Dab2 knockout mice is caused by suboptimal
      trafficking of megalin, leading to decreased megalin levels.

PMID- 15870385
TI  - In situ oligonucleotide synthesis on poly(dimethylsiloxane): a flexible substrate
      for microarray fabrication.
AB  - In this paper, we demonstrate in situ synthesis of oligonucleotide probes on
      poly(dimethylsiloxane) (PDMS) microchannels through use of conventional
      phosphoramidite chemistry. PDMS polymer was moulded into a series of
      microchannels using standard soft lithography (micro-moulding), with dimensions
      <100 microm. The surface of the PDMS was derivatized by exposure to
      ultraviolet/ozone followed by vapour phase deposition of
      glycidoxypropyltrimethoxysilane and reaction with poly(ethylene glycol) spacer,
      resulting in a reactive surface for oligonucleotide coupling. High, reproducible
      yields were achieved for both 6mer and 21mer probes as assessed by hybridization
      to fluorescent oligonucleotides. Oligonucleotide surface density was comparable
      with that obtained on glass substrates. These results suggest PDMS as a stable
      and flexible alternative to glass as a suitable substrate in the fabrication and
      synthesis of DNA microarrays.

PMID- 15870386
TI  - How many clones need to be sequenced from a single forensic or ancient DNA sample
      in order to determine a reliable consensus sequence?
AB  - Forensic and ancient DNA (aDNA) extracts are mixtures of endogenous aDNA,
      existing in more or less damaged state, and contaminant DNA. To obtain the true
      aDNA sequence, it is not sufficient to generate a single direct sequence of the
      mixture, even where the authentic aDNA is the most abundant (e.g. 25% or more) in
      the component mixture. Only bacterial cloning can elucidate the components of
      this mixture. We calculate the number of clones that need to be sampled (for
      various mixture ratios) in order to be confident (at various levels of
      confidence) to have identified the major component. We demonstrate that to be
      >95% confident of identifying the most abundant sequence present at 70% in the
      ancient sample, 20 clones must be sampled. We make recommendations and offer a
      free-access web-based program, which constructs the most reliable consensus
      sequence from the user's input clone sequences and analyses the confidence limits
      for each nucleotide position and for the whole consensus sequence. Accepted
      authentication methods must be employed in order to assess the authenticity and
      endogeneity of the resulting consensus sequences (e.g. quantification and
      replication by another laboratory, blind testing, amelogenin sex versus
      morphological sex, the effective use of controls, etc.) and determine whether
      they are indeed aDNA.

PMID- 15870387
TI  - The catalytic mechanism of hairpin ribozyme studied by hydrostatic pressure.
AB  - The discovery of ribozymes strengthened the RNA world hypothesis, which assumes
      that these precursors of modern life both stored information and acted as
      catalysts. For the first time among extensive studies on ribozymes, we have
      investigated the influence of hydrostatic pressure on the hairpin ribozyme
      catalytic activity. High pressures are of interest when studying life under
      extreme conditions and may help to understand the behavior of macromolecules at
      the origins of life. Kinetic studies of the hairpin ribozyme self-cleavage were
      performed under high hydrostatic pressure. The activation volume of the reaction
      (34 +/- 5 ml/mol) calculated from these experiments is of the same order of
      magnitude as those of common protein enzymes, and reflects an important
      compaction of the RNA molecule during catalysis, associated to a water release.
      Kinetic studies were also carried out under osmotic pressure and confirmed this
      interpretation and the involvement of water movements (78 +/- 4 water molecules
      per RNA molecule). Taken together, these results are consistent with structural
      studies indicating that loops A and B of the ribozyme come into close contact
      during the formation of the transition state. While validating baro-biochemistry
      as an efficient tool for investigating dynamics at work during RNA catalysis,
      these results provide a complementary view of ribozyme catalytic mechanisms.

PMID- 15870388
TI  - Angiopoietin-2 causes inflammation in vivo by promoting vascular leakage.
AB  - Angiopoietins (Angs) are endothelium-selective ligands that exert most of their
      actions through the Tie-2 receptor. It is widely accepted that Ang-1 promotes the
      structural integrity of blood vessels and exhibits anti-inflammatory properties.
      In contrast, the role of Ang-2 remains less clear because it has been shown to
      behave as a Tie-2 agonist or antagonist under different experimental conditions.
      To define the role of Ang-2 in acute inflammation, we studied the effects of
      recombinant Ang-2 administration in vivo. We show herein that Ang-2, but not Ang
      1, induces edema formation in the mouse paw in a dose-dependent manner; the edema
      seems to be fast-peaking (maximum at 30 min) and resolves within 4 h. The effect
      of Ang-2 is blocked by the coadministration with a soluble form of the Tie-2
      receptor or Ang-1. NO and prostaglandin E(2) levels in mouse paw following the
      injection of Ang-2 remained unaltered, suggesting that the action of Ang-2 does
      not involve these mediators. In addition, Ang-2 exerted a weak stimulatory effect
      on leukocyte migration in the mouse paw. Similarly, Ang-2 injected into the mouse
      air pouch produced only a modest effect on cell extravasation that peaked at 30
      min. However, when cell migration was elicited using zymosan, Ang-2 significantly
      inhibited leukocyte migration. We conclude that Ang-2 by itself stimulates the
      extravasation of cell-poor fluid, but in the presence of ongoing inflammation it
      reduces cellular infiltration in tissues.

PMID- 15870389
TI  - A novel celecoxib derivative potently induces apoptosis of human synovial
      fibroblasts.
AB  - We have already demonstrated that celecoxib, a selective cyclooxygenase (COX)-2
      inhibitor, has a proapoptotic effect on synovial fibroblasts obtained from
      patients with rheumatoid arthritis (RA). Here we report on the development of two
      novel derivatives of celecoxib, N-(2-aminoethyl)-4-[5-(4-tolyl)-3
      (trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (TT101) and 4-[5-(4
      aminophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (TT201),
      including whether these compounds have a proapoptotic effect on synovial
      fibroblasts. Synovial fibroblasts were harvested from the synovial tissues of
      patients with RA or osteoarthritis (OA). Cell proliferation and cell viability
      were assessed by the incorporation of 5-bromo-2'-deoxyuridine and by the 2-(4
      iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium
      salt assay, respectively. Apoptosis was detected by the identification of DNA
      fragmentation, and activation of caspase-3 was detected by the addition of a
      caspase-3 substrate to cell lysates. Production of prostaglandin E(2) by RA
      synovial fibroblasts was analyzed by enzyme-linked immunosorbent assay. TT101
      inhibited the proliferation of RA and OA synovial fibroblasts in a concentration
      dependent manner. It caused a marked decrease of cell viability and induced DNA
      fragmentation more potently than either celecoxib or SC-236 (4-[5-(4
      chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide). TT101 also
      increased caspase-3 activity. The order of potency of the COX-2 inhibitory
      activity of these drugs in RA synovial fibroblasts was celecoxib = SC-236 >
      rofecoxib > TT201 > TT101. In conclusion, we developed TT101 with about a 5- to
      10-fold stronger proapoptotic effect on RA and OA synovial fibroblasts compared
      with that of celecoxib. Although the mechanism of action of TT101 remains
      unclear, it may have potential as a novel antirheumatic agent.

PMID- 15870390
TI  - Role of N-terminal amino acids in the absorption-enhancing effects of the c
      terminal fragment of Clostridium perfringens enterotoxin.
AB  - We recently found that a polypeptide, the C-terminal of Clostridium perfringens
      enterotoxin (C-CPE), was a novel type of drug absorption enhancer. The C-terminal
      of C-CPE is thought to play a role in the binding of C-CPE to its receptor,
      claudin-4; however, the function of the N-terminal of C-CPE is unclear. In the
      present study, we evaluated the role of the N-terminal domain of C-CPE in jejunal
      absorption and claudin-4 binding. The treatment of rat jejunum with C-CPE
      resulted in enhanced absorption of dextran, with a molecular weight of 4000 Da.
      However, treatment with C-CPE220, which lacks the 36 N-terminal amino acids of C
      CPE, did not enhance jejunal absorption. C-CPE had affinity for claudin-4 in rat
      jejunum lysates and Caco-2 lysates, but C-CPE220 did not. Interaction of C-CPE
      with the recombinant extracellular domain 2 of human claudin-4 (EC2hCld-4), which
      is the putative binding site for C-CPE, was observed, but C-CPE220 had no
      affinity for EC2hCld-4. To investigate the effect of C-CPE220 on the barrier
      function of tight junctions, we measured transepithelial electric resistance
      (TER) in C-CPE- or C-CPE220-treated Caco-2 monolayer cells. Although C-CPE
      decreased TER in Caco-2 monolayer cells, C-CPE220 did not disrupt the barrier
      function of tight junctions. Together, these results indicate that the 36 N
      terminal amino acids of C-CPE may be necessary for the enhanced absorption
      mediated by C-CPE and play a partial role in binding to claudin-4.

PMID- 15870391
TI  - Barakol extracted from Cassia siamea stimulates chloride secretion in rat colon.
AB  - Barakol is a purified extract of Cassia siamea, a plant that has been used as a
      laxative in traditional medicine. In this study, the effect of barakol on anion
      transport across the rat colon epithelium was investigated. Colonic epithelium
      was mounted in Ussing chambers and bathed with Ringer's solution. Addition of 1
      mM barakol to the basolateral solution produced a slow increase in short-circuit
      current (Isc) in proximal colon and distal colon by 24.5 +/- 2.2 and 24.2 +/- 1.4
      microA/cm(2), respectively. Barakol increased Isc in a concentration-dependent
      manner with an EC(50) value of 0.4 mM. The barakol-stimulated increase in Isc was
      inhibited by subsequent treatment with 500 microM diphenylamine-2-carboxylic acid
      or 400 microM glibenclamide added to the apical solution and 200 microM
      bumetanide added to the basolateral solution. Pretreatment of the tissues with
      200 microM bumetanide, but not 10 microM amiloride, completely abolished the
      barakol-increased Isc. Ion substitution experiments showed an inhibition of
      barakol-stimulated Isc in chloride-free solution but not in bicarbonate-free
      solution. In addition, pretreatment of tissues with 10 microM tetrodotoxin or 10
      microM indomethacin, but not 1 microM atropine or 10 microM hexamethonium,
      partially inhibited the Isc response by barakol. The present results demonstrated
      the stimulatory effect of barakol on the bumetanide-sensitive chloride secretion
      in rat colon. The effect of barakol was partly mediated by the stimulation of
      submucosal nerves and through the release of cyclooxygenase metabolites. These
      findings thus provide an explanation for the underlying mechanism of barakol as a
      secretagogue in mammalian colon.

PMID- 15870392
TI  - Identification of indole derivatives exclusively interfering with a G protein
      independent signaling pathway of the prostaglandin D2 receptor CRTH2.
AB  - The anti-inflammatory drugs indomethacin and ramatroban, the latter showing
      clinical efficacy in treating allergic asthma, have been shown to act as a
      classic agonist and antagonist, respectively, of the G protein-coupled
      chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2
      receptor). Here, we report the identification of two indole derivatives 1-(4
      ethoxyphenyl)-5-methoxy-2-methylindole-3-carboxylic acid and N(alpha)
      tosyltryptophan (hereafter referred to as 1 and 2, respectively), which are
      structurally related to indomethacin and ramatroban but which selectively
      interfere with a specific G protein-independent signaling pathway of CRTH2. In
      whole-cell saturation-binding assays, 1 and 2 both increase the number of
      [(3)H]prostaglandin D2 (PGD2)-recognizing CRTH2 sites and the affinity of PGD2
      for CRTH2. Enzyme-linked immunosorbent assays show that they do not alter the
      total number of CRTH2 receptors on the cell surface. Analysis of their binding
      mode indicates that unlike indomethacin or ramatroban, 1 and 2 can occupy CRTH2
      simultaneously with PGD2. On a functional level, however, 1 and 2 do not
      interfere with PGD2-mediated activation of heterotrimeric G proteins by CRTH2. In
      contrast, both compounds inhibit PGD2-mediated arrestin translocation via a G
      protein-independent mechanism. In human eosinophils endogenously expressing
      CRTH2, 1 selectively decreases the efficacy but not the potency of PGD2-induced
      shape change, unlike ramatroban, which displays competitive antagonistic
      behavior. These data show for the first time that "antagonists" can cause
      markedly dissimilar degrees of inhibition for different effector pathways and
      suggest that it may be possible to develop novel classes of specific signal
      inhibiting drugs distinct from conventional antagonists.

PMID- 15870393
TI  - Genetic modifiers interact with Cpe(fat) to affect body weight, adiposity, and
      hyperglycemia.
AB  - Obesity and Type II diabetes are complex diseases in the human population. The
      existence of a large number of contributing loci and gene-gene as well as gene
      environment interactions make it difficult to identify the disease genes
      underlying these complex traits. In mouse models of obesity and Type II diabetes
      such as the murine fat mutation, genetic crosses can be used to dissect the
      genetic complexity influencing the observed phenotypes. The underlying defect in
      the fat mutant is a Ser202Pro change in carboxypeptidase E (CPE), an enzyme
      responsible for the final proteolytic processing step of prohormone
      intermediates. On the HRS/J (HRS) inbred strain background, mice homozygous for
      the fat mutation exhibit early onset hyperinsulinemia followed by postpubertal
      moderate obesity without hyperglycemia. In contrast, on the C57BLKS/J (BKS)
      genetic background, fat/fat mice become severely obese, hyperinsulinemic, and
      hyperglycemic. Therefore, in the Cpe(fat) genetic model, the fat mutation is
      necessary but not sufficient for the development of obesity, Type II diabetes,
      and related metabolic disorders. To dissect the susceptibility loci responsible
      for modifying obesity- and diabetes-associated traits, we characterized, both
      genetically and phenotypically, fat/fat male progeny from a large intercross
      between BKS. HRS-fat/fat and HRS-+/+ mice. Four major loci were mapped, including
      a locus for body weight (body weight 1) on chromosome 14; a locus for
      hyperglycemia (fat-induced diabetes 1) on chromosome 19; a locus for
      hyperglycemia, hyperinsulinemia, and hypercholesterolemia (fat-induced diabetes
      2) on chromosome 5; and a locus for adiposity and body weight (fat-induced
      adiposity 1) on chromosome 11. The identification of these interacting genetic
      determinants for obesity and Type II diabetes may allow better definition of the
      obesity/diabetes-related hormone signaling pathways and ultimately may provide
      new insights into the pathogenesis of these complex diseases.

PMID- 15870394
TI  - Type 2 diabetes mouse model TallyHo carries an obesity gene on chromosome 6 that
      exaggerates dietary obesity.
AB  - The TallyHo (TH) mouse strain is a polygenic model for Type 2 diabetes with
      obesity. Genetic analysis in backcross progeny from a cross between F1 [C57BL/6J
      (B6) x TH] and TH mice mapped a quantitative trait locus (QTL) named TH
      associated body weight 2 (tabw2) to chromosome 6. The TH-derived allele is
      associated with increased body weight. As a first step to identify the molecular
      basis of this obesity QTL, we constructed a congenic line of mice on the B6
      genetic background that carries a genomic region from TH mice containing tabw2.
      Congenic mice homozygous for tabw2 (B6.TH-tabw2/tabw2) fed a chow diet exhibited
      slightly, but significantly, higher body weight and body fat and plasma leptin
      levels compared with controls (B6.TH-+/+). This difference was exacerbated when
      the animals were maintained on a high-fat and high-sucrose (HFS) diet. The diet
      induced obesity in tabw2 congenic mice is accompanied by hyperleptinemia, mild
      hyperinsulinemia, impaired glucose tolerance, and reduced glucose uptake in
      adipose tissue in response to insulin administration. Using F2 progeny fed a HFS
      diet from an intercross of B6.TH-tabw2/+ mice, we were able to refine the map
      position of the tabw2 obesity susceptibility locus to a 15-cM region (95%
      confidence interval) extending distally from the marker D6Mit102. In summary,
      tabw2 congenic mice are a new animal model for diet-induced obesity that will be
      valuable for the study of gene-diet interactions.

PMID- 15870395
TI  - Genome-wide analysis of gene transcription in the hypothalamus.
AB  - As the genomic regions containing loci predisposing to obesity-related traits are
      mapped in human population screens and mouse genetic studies, identification of
      susceptibility genes will increasingly be facilitated by bioinformatic methods.
      We hypothesized that candidate genes can be prioritized by their expression
      levels in tissues of central importance in obesity. Our objective was to develop
      a combined bioinformatics and molecular paradigm to identify novel genes as
      candidates for murine or human obesity genetic modifiers based on their
      differential expression patterns in the hypothalamus compared with other murine
      tissues. We used bioinformatics tools to search publicly available gene
      expression databases using criteria designed to identify novel genes
      differentially expressed in the hypothalamus. We used RNA methods to determine
      their expression sites and levels of expression in the hypothalamus of the murine
      brain. We identified the chromosomal location of the novel genes in mice and in
      humans and compared these locations with those of genetic loci predisposing to
      obesity-related traits. We developed a search strategy that correctly identified
      a set of genes known to be important in hypothalamic function as well as a
      candidate gene for Prader-Willi syndrome that was not previously identified as
      differentially expressed in the hypothalamus. Using this same strategy, we
      identified and characterized a set of 11 genes not previously known to be
      differentially expressed in the murine hypothalamus. Our results demonstrate the
      feasibility of combined bioinformatics and molecular approaches to the
      identification of genes that are candidates for obesity-related disorders in
      humans and mice.

PMID- 15870396
TI  - Linkage and association analyses of the UCP3 gene with obesity phenotypes in
      Caucasian families.
AB  - Uncoupling protein 3 (UCP3) uncouples ATP production from mitochondrial
      respiration, thereby dissipating energy as heat and affecting the efficiency of
      energy metabolism. Genetic variations in the UCP3 gene have been conceived to
      affect body weight in the general population. In this study, using the
      quantitative transmission disequilibrium test (QTDT), we assessed linkage and
      association between the UCP3 gene and obesity phenotypes in a large sample of
      1,873 subjects from 405 United States Caucasian nuclear families. Obesity
      phenotypes tested include body mass index (BMI), fat mass, percent fat mass
      (PFM), and lean mass, with the latter three measured by dual-energy X-ray
      absorptiometry. We first selected five single nucleotide polymorphisms (SNPs) and
      then analyzed three highly polymorphic ones, namely, -55 C/T (promoter), Tyr99Tyr
      (exon 3), and Tyr210Tyr (exon 5), in the total sample. Significant linkage
      disequilibria (0.392 <or= D' <or= 0.940, P < 0.0001) were observed between pairs
      of SNPs. In single-locus analyses, we found statistically significant association
      (P = 0.034) and linkage (P = 0.031) between -55 C/T and BMI. This polymorphism
      explains 2.29% of BMI variation, and subjects carrying the T allele had an
      average of 3.5% lower BMI than those without it (P = 0.003). In haplotype
      analyses, we also observed evidence of linkage (P = 0.002) and association (P =
      0.035) with BMI. In summary, our results suggest that UCP3 gene polymorphisms may
      contribute to BMI variation in this Caucasian population.

PMID- 15870397
TI  - Profiling of differentially expressed genes in wound margin biopsies of horses
      using suppression subtractive hybridization.
AB  - Disturbed gene expression may disrupt the normal process of repair and lead to
      pathological situations resulting in excessive scarring. To prevent and treat
      impaired healing, it is necessary to first define baseline gene expression during
      normal repair. The objective of this study was to compare gene expression in
      normal intact skin (IS) and wound margin (WM) biopsies using suppression
      subtractive hybridization (SSH) to identify genes differentially expressed during
      wound repair in horses. Tissue samples included both normal IS and biopsies from
      7-day-old wounds. IS cDNAs were subtracted from WM cDNAs to establish a
      subtracted (WM-IS) cDNA library; 226 nonredundant cDNAs were identified.
      Detection of genes previously shown to be expressed 7 days after trauma,
      including the pro-alpha(2)-chain of type 1 pro-collagen (COL1A2), annexin A(2),
      the pro-alpha(3)-chain of type 6 pro-collagen, beta-actin, fibroblast growth
      factor 7, laminin receptor 1, matrix metalloproteinase 1 (MMP1), secreted protein
      acidic cystein rich, and tissue inhibitor of metalloproteinase 2, supported the
      validity of the experimental design. A RT-PCR assay confirmed an increase or
      induction of the cDNAs of specific genes (COL1A2, MMP1, dermatan sulfate
      proteoglycan 2, cluster differentiation 68, cluster differentiation 163, and
      disintegrin and metalloproteinase domain 9) within wound biopsies. Among these,
      COL1A2 and MMP1 had previously been documented in horses; 68.8% of the cDNAs had
      not previously been attributed a role during wound repair, of which
      spermidine/spermine-N-acetyltransferase, serin proteinase inhibitor B10, and
      sorting nexin 9 were highly expressed and whose known functions in other
      processes made them potential candidates in regulating the proliferative response
      to wounding. In conclusion, we identified novel genes that are differentially
      expressed in equine wound biopsies and that may modulate repair. Future
      experiments must correlate changes in mRNA levels for precise molecules with
      spatiotemporal protein expression within tissues.

PMID- 15870399
TI  - The cover. The family.

PMID- 15870398
TI  - Signature patterns of gene expression in mouse atherosclerosis and their
      correlation to human coronary disease.
AB  - The propensity for developing atherosclerosis is dependent on underlying genetic
      risk and varies as a function of age and exposure to environmental risk factors.
      Employing three mouse models with different disease susceptibility, two diets,
      and a longitudinal experimental design, it was possible to manipulate each of
      these factors to focus analysis on genes most likely to have a specific disease
      related function. To identify differences in longitudinal gene expression
      patterns of atherosclerosis, we have developed and employed a statistical
      algorithm that relies on generalized regression and permutation analysis.
      Comprehensive annotation of the array with ontology and pathway terms has allowed
      rigorous identification of molecular and biological processes that underlie
      disease pathophysiology. The repertoire of atherosclerosis-related
      immunomodulatory genes has been extended, and additional fundamental pathways
      have been identified. This highly disease-specific group of mouse genes was
      combined with an extensive human coronary artery data set to identify a shared
      group of genes differentially regulated among atherosclerotic tissues from
      different species and different vascular beds. A small core subset of these
      differentially regulated genes was sufficient to accurately classify various
      stages of the disease in mouse. The same gene subset was also found to accurately
      classify human coronary lesion severity. In addition, this classifier gene set
      was able to distinguish with high accuracy atherectomy specimens from native
      coronary artery disease vs. those collected from in-stent restenosis lesions,
      thus identifying molecular differences between these two processes. These studies
      significantly focus efforts aimed at identifying central gene regulatory pathways
      that mediate atherosclerotic disease, and the identification of classification
      gene sets offers unique insights into potential diagnostic and therapeutic
      strategies in atherosclerotic disease.

PMID- 15870400
TI  - New home for nation's research hospital: NIH opens Mark O. Hatfield Clinical
      Research Center.

PMID- 15870401
TI  - Reducing HIV vertical transmission scrutinized.

PMID- 15870402
TI  - Heart risk rises with long-term HIV drugs.

PMID- 15870403
TI  - New Howard Hughes investigators named.

PMID- 15870404
TI  - Breaking barriers in transdermal drug delivery.

PMID- 15870407
TI  - Exposure to infant siblings during early life and risk of multiple sclerosis.

PMID- 15870408
TI  - Quality of cardiopulmonary resuscitation.

PMID- 15870409
TI  - Virtual reality training for carotid stenting.

PMID- 15870410
TI  - Use of niacin during non-ST-segment elevation acute coronary syndromes.

PMID- 15870411
TI  - Economic behavior and informed consent.

PMID- 15870412
TI  - 20-year outcomes following conservative management of clinically localized
      prostate cancer.
AB  - CONTEXT: The appropriate therapy for men with clinically localized prostate
      cancer is uncertain. A recent study suggested an increasing prostate cancer
      mortality rate for men who are alive more than 15 years following diagnosis.
      OBJECTIVE: To estimate 20-year survival based on a competing risk analysis of men
      who were diagnosed with clinically localized prostate cancer and treated with
      observation or androgen withdrawal therapy alone, stratified by age at diagnosis
      and histological findings. DESIGN, SETTING, AND PATIENTS: A retrospective
      population-based cohort study using Connecticut Tumor Registry data supplemented
      by hospital record and histology review of 767 men aged 55 to 74 years with
      clinically localized prostate cancer diagnosed between January 1, 1971, and
      December 31, 1984. Patients were treated with either observation or immediate or
      delayed androgen withdrawal therapy, with a median observation of 24 years. MAIN
      OUTCOME MEASURES: Probability of mortality from prostate cancer or other
      competing medical conditions, given a patient's age at diagnosis and tumor grade.
      RESULTS: The prostate cancer mortality rate was 33 per 1000 person-years during
      the first 15 years of follow-up (95% confidence interval [CI], 28-38) and 18 per
      1000 person-years after 15 years of follow-up (95% CI, 10-29). The mortality
      rates for these 2 follow-up periods were not statistically different, after
      adjusting for differences in tumor histology (rate ratio, 1.1; 95% CI, 0.6-1.9).
      Men with low-grade prostate cancers have a minimal risk of dying from prostate
      cancer during 20 years of follow-up (Gleason score of 2-4, 6 deaths per 1000
      person-years; 95% CI, 2-11). Men with high-grade prostate cancers have a high
      probability of dying from prostate cancer within 10 years of diagnosis (Gleason
      score of 8-10, 121 deaths per 1000 person-years; 95% CI, 90-156). Men with
      Gleason score of 5 or 6 tumors have an intermediate risk of prostate cancer
      death. CONCLUSION: The annual mortality rate from prostate cancer appears to
      remain stable after 15 years from diagnosis, which does not support aggressive
      treatment for localized low-grade prostate cancer.

PMID- 15870413
TI  - Bone mineral density and the risk of incident nonspinal fractures in black and
      white women.
AB  - CONTEXT: Black women have a lower rate of fracture than white women, but whether
      bone mineral density (BMD) predicts fracture risk as well in black women as it
      does in white women is not established. OBJECTIVE: To examine the association
      between BMD and incident nonspinal fractures in older black and white women.
      DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of baseline data
      collected from 1986 through 1990 (7334 white women aged 67-99 years) and from
      1996 through 1998 (636 black women aged 65-94 years) at 4 US clinical centers in
      the Study of Osteoporotic Fractures; mean (SD) follow-up of 6.1 (1.5) years until
      October 1, 2004. MAIN OUTCOME MEASURES: Incident nonspinal fractures were
      confirmed by radiograpic report. Total hip and femoral neck BMD and bone mineral
      content were measured by dual energy x-ray absorptiometry. RESULTS: A total of 58
      black women had a combined total of 61 fractures and 1606 white women had a
      combined total of 1712 fractures. In age-adjusted proportional hazard models, a 1
      SD decrease in femoral neck BMD was associated with a 37% increased risk of
      fracture in black women (relative risk [RR], 1.37; 95% confidence interval [CI],
      1.08-1.74) and a 49% increase in fracture in white women (RR, 1.49; 95% CI, 1.40
      1.58). Adjustment for body weight and other risk factors for fracture weakened
      the association between BMD and fracture, especially among black women
      (multivariable adjusted RR per 1-SD decrease in femoral neck BMD for black vs
      white women: RR, 1.20 [95% CI, 0.93-1.55] vs RR, 1.42 [95% CI, 1.32-1.52]). The
      absolute incidence of fracture across the pooled BMD distribution was 30% to 40%
      lower among black women at every BMD tertile. The lower risk of fracture among
      black compared with white women was independent of BMD and other risk factors
      (RR, 0.48; 95% CI, 0.36-0.64). CONCLUSIONS: Decreased total hip and femoral neck
      BMD is associated with an increased risk of fracture in both older black and
      white women, but this relationship was largely explained by other risk factors in
      black women. Black women have a lower fracture risk than white women at every
      level of BMD. Race-specific normative databases may be appropriate for the
      densitometric definition of osteoporosis.

PMID- 15870414
TI  - Tirofiban and sirolimus-eluting stent vs abciximab and bare-metal stent for acute
      myocardial infarction: a randomized trial.
AB  - CONTEXT: Bare-metal stenting with abciximab pretreatment is currently considered
      a reasonable reperfusion strategy for acute ST-segment elevation myocardial
      infarction (STEMI). Sirolimus-eluting stents significantly reduce the need for
      target-vessel revascularization (TVR) vs bare-metal stents but substantially
      increase procedural costs. At current European list prices, the use of tirofiban
      instead of abciximab would absorb the difference in cost between stenting with
      sirolimus-eluting vs bare-metal stents. OBJECTIVE: To evaluate the clinical and
      angiographic impact of single high-dose bolus tirofiban plus sirolimus-eluting
      stenting vs abciximab plus bare-metal stenting in patients with STEMI. DESIGN,
      SETTING, AND PATIENTS: Prospective, single-blind, randomized controlled study
      (Single High Dose Bolus Tirofiban and Sirolimus Eluting Stent vs Abciximab and
      Bare Metal Stent in Myocardial Infarction [STRATEGY]) of 175 patients (median
      age, 63 [interquartile range, 55-72] years) presenting to a single referral
      center in Italy with STEMI or presumed new left bundle-branch block and
      randomized between March 6, 2003, and April 23, 2004. INTERVENTION: Single high
      dose bolus tirofiban regimen plus sirolimus-eluting stenting (n = 87) vs standard
      dose abciximab plus bare-metal stenting (n = 88). MAIN OUTCOME MEASURES: The
      primary end point was a composite of death, nonfatal myocardial infarction,
      stroke, or binary restenosis at 8 months. Secondary outcomes included freedom, at
      day 30 and month 8, from major cardiac or cerebrovascular adverse events
      (composite of death, reinfarction, stroke, and repeat TVR). RESULTS:
      Cumulatively, 14 of 74 patients (19%; 95% confidence interval [CI], 10%-28%) in
      the tirofiban plus sirolimus-eluting stent group and 37 of 74 patients (50%; 95%
      CI, 44%-56%) in the abciximab plus bare-metal stent group reached the primary end
      point (hazard ratio, 0.33; 95% CI, 0.18-0.60; P<.001 [P<.001 by Fischer exact
      test]). The cumulative incidence of death, reinfarction, stroke, or TVR was
      significantly lower in the tirofiban plus sirolimus-eluting stent group (18%) vs
      the abciximab plus bare-metal stent group (32%) (hazard ratio, 0.53; 95% CI, 0.28
      0.92; P = .04), predominantly reflecting a reduction in the need for TVR. Binary
      restenosis was present in 6 of 67 (9%; 95% CI, 2%-16%) and 24 of 66 (36%; 95% CI,
      26%-46%) patients in the tirofiban plus sirolimus-eluting stent and abciximab
      plus bare-metal stent groups, respectively (P = .002). CONCLUSION: Tirofiban
      supported sirolimus-eluting stenting of infarcted arteries holds promise for
      improving outcomes while limiting health care expenditure in patients with
      myocardial infarction undergoing primary intervention.

PMID- 15870415
TI  - Acupuncture for patients with migraine: a randomized controlled trial.
AB  - CONTEXT: Acupuncture is widely used to prevent migraine attacks, but the
      available evidence of its benefit is scarce. OBJECTIVE: To investigate the
      effectiveness of acupuncture compared with sham acupuncture and with no
      acupuncture in patients with migraine. DESIGN, SETTING, AND PATIENTS: Three
      group, randomized, controlled trial (April 2002-January 2003) involving 302
      patients (88% women), mean (SD) age of 43 (11) years, with migraine headaches,
      based on International Headache Society criteria. Patients were treated at 18
      outpatient centers in Germany. INTERVENTIONS: Acupuncture, sham acupuncture, or
      waiting list control. Acupuncture and sham acupuncture were administered by
      specialized physicians and consisted of 12 sessions per patient over 8 weeks.
      Patients completed headache diaries from 4 weeks before to 12 weeks after
      randomization and from week 21 to 24 after randomization. MAIN OUTCOME MEASURES:
      Difference in headache days of moderate or severe intensity between the 4 weeks
      before and weeks 9 to 12 after randomization. RESULTS: Between baseline and weeks
      9 to 12, the mean (SD) number of days with headache of moderate or severe
      intensity decreased by 2.2 (2.7) days from a baseline of 5.2 (2.5) days in the
      acupuncture group compared with a decrease to 2.2 (2.7) days from a baseline of
      5.0 (2.4) days in the sham acupuncture group, and by 0.8 (2.0) days from a
      baseline if 5.4 (3.0) days in the waiting list group. No difference was detected
      between the acupuncture and the sham acupuncture groups (0.0 days, 95% confidence
      interval, -0.7 to 0.7 days; P = .96) while there was a difference between the
      acupuncture group compared with the waiting list group (1.4 days; 95% confidence
      interval; 0.8-2.1 days; P<.001). The proportion of responders (reduction in
      headache days by at least 50%) was 51% in the acupuncture group, 53% in the sham
      acupuncture group, and 15% in the waiting list group. CONCLUSION: Acupuncture was
      no more effective than sham acupuncture in reducing migraine headaches although
      both interventions were more effective than a waiting list control.

PMID- 15870416
TI  - Incidence, predictors, and outcome of thrombosis after successful implantation of
      drug-eluting stents.
AB  - CONTEXT: Traditionally, stent thrombosis has been regarded as a complication of
      percutaneous coronary interventions during the first 30 postprocedural days.
      However, delayed endothelialization associated with the implantation of drug
      eluting stents may extend the risk of thrombosis beyond 30 days. Data are limited
      regarding the risks and the impact of this phenomenon outside clinical trials.
      OBJECTIVE: To evaluate the incidence, predictors, and clinical outcome of stent
      thrombosis after implantation of sirolimus-eluting and paclitaxel-eluting stents
      in routine clinical practice. DESIGN, SETTING, AND PATIENTS: Prospective
      observational cohort study conducted at 1 academic hospital and 2 community
      hospitals in Germany and Italy. A total of 2229 consecutive patients underwent
      successful implantation of sirolimus-eluting (1062 patients, 1996 lesions, 2272
      stents) or paclitaxel-eluting (1167 patients, 1801 lesions, 2223 stents) stents
      between April 2002 and January 2004. INTERVENTIONS: Implantation of a drug
      eluting stent (sirolimus or paclitaxel). All patients were pretreated with
      ticlopidine or clopidogrel and aspirin. Aspirin was continued indefinitely and
      clopidogrel or ticlopidine for at least 3 months after sirolimus-eluting and for
      at least 6 months after paclitaxel-eluting stent implantation. MAIN OUTCOME
      MEASURES: Subacute thrombosis (from procedure end through 30 days), late
      thrombosis (>30 days), and cumulative stent thrombosis. RESULTS: At 9-month
      follow-up, 29 patients (1.3%) had stent thrombosis (9 [0.8%] with sirolimus and
      20 [1.7%] with paclitaxel; P = .09). Fourteen patients had subacute thrombosis
      (0.6%) and 15 patients had late thrombosis (0.7%). Among these 29 patients, 13
      died (case fatality rate, 45%). Independent predictors of stent thrombosis were
      premature antiplatelet therapy discontinuation (hazard ratio [HR], 89.78; 95% CI,
      29.90-269.60; P<.001), renal failure (HR, 6.49; 95% CI, 2.60-16.15; P<.001),
      bifurcation lesions (HR, 6.42; 95% CI, 2.93-14.07; P<.001), diabetes (HR, 3.71;
      95% CI, 1.74-7.89; P = .001), and a lower ejection fraction (HR, 1.09; 95% CI,
      1.05-1.36; P<.001 for each 10% decrease). CONCLUSIONS: The cumulative incidence
      of stent thrombosis 9 months after successful drug-eluting stent implantation in
      consecutive "real-world" patients was substantially higher than the rate reported
      in clinical trials. Premature antiplatelet therapy discontinuation, renal
      failure, bifurcation lesions, diabetes, and low ejection fraction were identified
      as predictors of thrombotic events.

PMID- 15870417
TI  - The Research on Adverse Drug Events and Reports (RADAR) project.
AB  - CONTEXT: In 1998, a multidisciplinary team of investigators initiated RADAR
      (Research on Adverse Drug events And Reports), a clinically based postmarketing
      surveillance program that systematically investigates and disseminates
      information describing serious and previously unrecognized adverse drug and
      device reactions (ADRs). OBJECTIVE: To describe the structure, operations, and
      preliminary findings from the RADAR project and related dissemination efforts by
      pharmaceutical suppliers and the US Food and Drug Administration (FDA). DESIGN:
      After identifying a serious and unexpected clinical event suitable for further
      investigation, RADAR collaborators postulated clinical hypotheses and derived
      case series and incidence estimates from physician queries, published and
      unpublished clinical trials, published case reports, FDA databases, and
      manufacturer sales figures. RESULTS: RADAR investigators identified 16 types of
      serious ADRs among 1699 patients, of whom 169 (10%) died as a result of the
      reaction. Initial cases were identified by 7 RADAR investigators, 4 collaborating
      physicians, 2 attorneys, and by reviewing 3 published reports. Additional sources
      included queries of occupational health programs and medical directors of
      interventional cardiology laboratories (3 types of ADRs), published manuscripts
      and clinical trials (11 types of ADRs), review of medical records at a RADAR site
      (2 types of ADRs), unpublished clinical trial reports (3 types of ADRs), and
      reports from attorneys, family members, or patients (4 types of ADRs). Incidence
      estimates, ranging from 0.4% to 33%, were derived from 5 clinical trial reports,
      2 physician queries, and 2 observational databases. Laboratory support for
      hypotheses included identification of 3 neutralizing antibodies and 3
      histopathological findings. ADR reports were disseminated as 8 revised package
      inserts, 7 "dear doctor" letters, and 9 peer-reviewed articles. CONCLUSION: A
      new, clinically based, hypothesis-driven approach to postmarketing surveillance
      may supplement existing regulatory surveillance systems and improve patient
      safety.

PMID- 15870418
TI  - Outcomes of routine episiotomy: a systematic review.
AB  - CONTEXT: Episiotomy at the time of vaginal birth is common. Practice patterns
      vary widely, as do professional opinions about maternal risks and benefits
      associated with routine use. OBJECTIVE: To systematically review the best
      evidence available about maternal outcomes of routine vs restrictive use of
      episiotomy. EVIDENCE ACQUISITION: We searched MEDLINE, Cumulative Index to
      Nursing and Allied Health Literature, and Cochrane Collaboration resources and
      performed a hand search for English-language articles from 1950 to 2004. We
      included randomized controlled trials of routine episiotomy or type of episiotomy
      that assessed outcomes in the first 3 postpartum months, along with trials and
      prospective studies that assessed longer-term outcomes. Twenty-six of 986
      screened articles provided relevant data. We entered data into abstraction forms
      and conducted a second review for accuracy. Each article was also scored for
      research quality. EVIDENCE SYNTHESIS: Fair to good evidence from clinical trials
      suggests that immediate maternal outcomes of routine episiotomy, including
      severity of perineal laceration, pain, and pain medication use, are not better
      than those with restrictive use. Evidence is insufficient to provide guidance on
      choice of midline vs mediolateral episiotomy. Evidence regarding long-term
      sequelae is fair to poor. Incontinence and pelvic floor outcomes have not been
      followed up into the age range in which women are most likely to have sequelae.
      With this caveat, relevant studies are consistent in demonstrating no benefit
      from episiotomy for prevention of fecal and urinary incontinence or pelvic floor
      relaxation. Likewise, no evidence suggests that episiotomy reduces impaired
      sexual function--pain with intercourse was more common among women with
      episiotomy. CONCLUSIONS: Evidence does not support maternal benefits
      traditionally ascribed to routine episiotomy. In fact, outcomes with episiotomy
      can be considered worse since some proportion of women who would have had lesser
      injury instead had a surgical incision.

PMID- 15870419
TI  - The natural history of clinically localized prostate cancer.

PMID- 15870420
TI  - Bone density and the risk of fractures: should treatment thresholds vary by race?

PMID- 15870421
TI  - Drug-eluting stents in acute myocardial infarction: is science catching up with
      practice?

PMID- 15870422
TI  - JAMA patient page. Childbirth.

PMID- 15870423
TI  - Membrane resealing: synaptotagmin VII keeps running the show.
AB  - Ca2+ influx, an immediate consequence of plasma membrane disruption, triggers a
      resealing mechanism involving exocytosis. Although this has been known for about
      a decade, a better understanding of the organelles involved and of the molecular
      machinery controlling membrane repair has been slower to emerge. Recent studies
      have changed this picture, by identifying lysosomes as exocytotic vesicles
      involved in membrane resealing and the Ca2+-binding protein synaptotagmin VII as
      a regulator of this process. New evidence reinforces the role of the C2A and C2B
      domains of synaptotagmin VII in plasma membrane repair, highlighting the
      importance of this molecule as a powerful tool for future studies.

PMID- 15870424
TI  - Sensing your surroundings: how transcription-regulatory networks of the cell
      discern environmental signals.
AB  - Accumulating evidence indicates that cells differentially regulate parts of their
      biochemical networks in various environmental conditions. Two recent studies,
      focused on the yeast transcription-regulatory network, have identified the
      characteristics and some of the regulatory logic that defines such conditional
      regulation on a system level. But what is the underlying basis of such
      environment-dependent dynamic network utilization? We propose that with
      simultaneous changes in many environmental variables, cells detect and process
      the incoming pieces of information individually with the use of receptors and
      sensor transcription factors specialized to a given type of signal. In turn,
      transcriptional subnetworks affected by the activity of these proteins reassemble
      the processed signals deeper inside the network, ultimately resulting in the
      development of an integrated cellular response.

PMID- 15870425
TI  - Teaching resources. TRP channels.
AB  - This Teaching Resource provides lecture notes and slides for a class covering TRP
      channels and is part of the course "Cell Signaling Systems: A Course for Graduate
      Students." The lecture begins with an overview of calcium signaling and then
      proceeds to describe the function, regulation, and activation of different TRP
      channel families.

PMID- 15870426
TI  - Medroxyprogesterone acetate and metastases: of mice and (wo)men.

PMID- 15870427
TI  - A curious link between epidermal growth factor receptor amplification and
      survival: effect of "allele dilution" on gefitinib sensitivity?

PMID- 15870428
TI  - When will the U.S. flinch at cancer drug prices?

PMID- 15870429
TI  - Blocking cancer with RNA interference moves toward the clinic.

PMID- 15870430
TI  - RNA-based nanoparticle treatment shows promise in Ewing's sarcoma model.

PMID- 15870431
TI  - For EGFR research, new targeted drugs mean new questions.

PMID- 15870432
TI  - Stat bite: Incidence of cervical cancer by ethnicity, 1992-2001.

PMID- 15870433
TI  - Vaccinating men for HPV: new strategy for preventing cervical cancer in women?

PMID- 15870434
TI  - Medroxyprogesterone acetate elevation of Nm23-H1 metastasis suppressor expression
      in hormone receptor-negative breast cancer.
AB  - BACKGROUND: Reestablishment of metastasis suppressor gene expression may
      constitute a therapeutic strategy for high-risk breast cancer patients. We
      previously showed that medroxyprogesterone acetate (MPA), a progestin that has
      been tested as treatment for advanced breast cancer, elevates expression of the
      Nm23-H1 metastasis suppressor gene in hormone receptor-negative metastatic human
      breast carcinoma cell lines in vitro via a glucocorticoid receptor-based
      mechanism. Here, we tested whether MPA treatment inhibits metastatic colonization
      of a hormone receptor-negative breast cancer cell line in vivo. METHODS: We
      tested the soft-agar colony-forming efficiency of untransfected MDA-MB-231T human
      breast carcinoma cells and MDA-MB-231T cells transfected with antisense Nm23-H1
      in the presence and absence of MPA. Pharmacokinetic studies were used to
      establish dose and injection schedules that led to MPA serum levels in mice
      similar to those achievable in humans. For in vivo studies, nude mice were
      injected intravenously with MDA-MB-231T cells. After 4 weeks, mice were
      randomized to control or MPA arms. Endpoints included incidence, number, and size
      of gross pulmonary metastases; Nm23-H1 protein expression in gross metastases;
      and side effects. All statistical tests were two-sided. RESULTS: MPA reduced
      colony formation of MDA-MB-231T cells by 40%-50% but had no effect on colony
      formation of Nm23-H1 antisense transfectants. Metastases developed in 100% (95%
      confidence interval [CI] = 78% to 100% and 77% to 100%, respectively) of control
      mice injected with MDA-MB-231T cells. In two independent experiments, only 73%
      (95% CI = 45% to 92%) and 64% (95% CI = 35% to 87%) of mice injected with 2 mg of
      MPA developed metastases. Mice injected with 2 mg of MPA showed reductions in the
      mean numbers, per mouse, of all metastases and of large (>3 mm) metastases (P =
      .04 and .013, respectively). Nm23-H1 was expressed at high levels in 43% of
      pulmonary metastases in MPA-treated mice but only 13% of metastases in untreated
      mice. Mice receiving at least 1-mg doses of MPA gained more weight than control
      treated mice but exhibited no bone density alterations or abnormal mammary fat
      pad histology. CONCLUSION: Our preclinical results show that MPA appears to
      elevate Nm23-H1 metastasis suppressor gene expression, thereby reducing
      metastatic colonization. The data suggest a new use for an old agent in a
      molecularly defined subset of breast cancer patients.

PMID- 15870435
TI  - Epidermal growth factor receptor gene and protein and gefitinib sensitivity in
      non-small-cell lung cancer.
AB  - BACKGROUND: Gefitinib is a selective inhibitor of the epidermal growth factor
      (EGFR) tyrosine kinase, which is overexpressed in many cancers, including non
      small-cell lung cancer (NSCLC). We carried out a clinical study to compare the
      relationship between EGFR gene copy number, EGFR protein expression, EGFR
      mutations, and Akt activation status as predictive markers for gefitinib therapy
      in advanced NSCLC. METHODS: Tumors from 102 NSCLC patients treated daily with 250
      mg of gefitinib were evaluated for EGFR status by fluorescence in situ
      hybridization (FISH), DNA sequencing, and immunohistochemistry and for Akt
      activation status (phospho-Akt [P-Akt]) by immunohistochemistry. Time to
      progression, overall survival, and 95% confidence intervals (CIs) were calculated
      and evaluated by the Kaplan-Meier method; groups were compared using the log-rank
      test. Risk factors associated with survival were evaluated using Cox proportional
      hazards regression modeling and multivariable analysis. All statistical tests
      were two-sided. RESULTS: Amplification or high polysomy of the EGFR gene (seen in
      33 of 102 patients) and high protein expression (seen in 58 of 98 patients) were
      statistically significantly associated with better response (36% versus 3%, mean
      difference = 34%, 95% CI = 16.6 to 50.3; P<.001), disease control rate (67%
      versus 26%, mean difference = 40.6%, 95% CI = 21.5 to 59.7; P<.001), time to
      progression (9.0 versus 2.5 months, mean difference = 6.5 months, 95% CI = 2.8 to
      10.3; P<.001), and survival (18.7 versus 7.0 months, mean difference = 11.7
      months, 95% CI = 2.1 to 21.4; P = .03). EGFR mutations (seen in 15 of 89
      patients) were also statistically significantly related to response and time to
      progression, but the association with survival was not statistically significant,
      and 40% of the patients with mutation had progressive disease. In multivariable
      analysis, only high EGFR gene copy number remained statistically significantly
      associated with better survival (hazard ratio = 0.44, 95% CI = 0.23 to 0.82).
      Independent of EGFR assessment method, EGFR+/P-Akt+ patients had a statistically
      significantly better outcome than EGFR-, P-Akt-, or EGFR+/P-Akt- patients.
      CONCLUSIONS: High EGFR gene copy number identified by FISH may be an effective
      molecular predictor for gefitinib efficacy in advanced NSCLC.

PMID- 15870436
TI  - Constitutively active K-cyclin/cdk6 kinase in Kaposi sarcoma-associated
      herpesvirus-infected cells.
AB  - BACKGROUND: Kaposi sarcoma-associated human herpesvirus (KSHV) encodes K-cyclin,
      a homologue of D-type cellular cyclins, which binds cyclin-dependent kinases to
      phosphorylate various substrates. K-cyclin/cdk phosphorylates a subset of
      substrates normally targeted by cyclins D, E, and A. We used cells naturally
      infected with KSHV to further characterize the biochemical features of K-cyclin.
      METHODS: We used immunoprecipitation with K-cyclin antibodies to examine the
      association of K-cyclin with cdk2, cdk6, p21Cip1, and p27Kip1 proteins in BC3
      cells. We separated populations of BC3 cells enriched in cells in G1, S, or G2/M
      phases by elutriation and measured K-cyclin protein and the kinase activity of K
      cyclin/cdk6 complexes. The half-life of K-cyclin and cyclin D2 proteins was
      determined by blocking protein synthesis with cycloheximide and measuring
      proteins in cell lysates by western blot analysis. We fused the entire K-cyclin
      sequence to the carboxyl-terminal sequence of cellular cyclin D that contains the
      PEST degradation sequence to produce K-cyclin/D2 and transfected K-cyclin/D2 into
      K-cyclin-negative cells to investigate the effect of the PEST sequence on K
      cyclin's stability. RESULTS: Viral K-cyclin interacted with cyclin-dependent
      kinases cdk2, cdk4, and cdk6 and with the cyclin/cdk inhibitory proteins p21Cip1
      and p27Kip1 in BC3 cell lysates. Unlike D-type cyclins, whose expression is cell
      cycle dependent, the level of K-cyclin was stable throughout the cell cycle, and
      the kinase associated with the K-cyclin/cdk6 complex was constitutively active.
      The half-life of K-cyclin (6.9 hours) was much longer than that of cellular
      cyclin D2 (0.6 hour) and that of K-cyclin/D2 (0.5 hour), probably because K
      cyclin lacks the PEST degradation sequence present in D-type cyclins. CONCLUSION:
      The constitutive activation of K-cyclin/cdk complexes in KSHV-infected cells
      appears to result from the extended half-life of K-cyclin and may explain its
      role in Kaposi sarcoma.

PMID- 15870437
TI  - Randomized phase III trial of dose-dense chemotherapy supported by whole-blood
      hematopoietic progenitors in better-prognosis small-cell lung cancer.
AB  - BACKGROUND: Recent dose-intensity studies of small-cell lung cancer (SCLC) have
      yielded conflicting results. We carried out a phase III randomized trial in
      patients with better-prognosis SCLC (i.e., prognostic score of 0-1) to
      investigate whether doubling the dose density of ifosfamide, carboplatin, and
      etoposide (ICE) chemotherapy with filgrastim and blood-progenitor-cell support
      improves survival, compared with standard ICE chemotherapy. METHODS: We studied
      318 patients with pathologically proven SCLC who were randomly assigned to
      receive six cycles of ICE chemotherapy with a 4-week (standard arm) or 2-week
      (dose-dense arm) interval between cycles. Patients in the dose-dense arm received
      filgrastim subcutaneously daily on days 4 through 14 and had autologous blood
      collected before cycles 2 through 6, which was returned 24 hours after treatment.
      Toxicities, including hematologic toxicity and incidence of neutropenic sepsis,
      were monitored. Survival was calculated by the Kaplan-Meier method. All
      statistical tests were two-sided. RESULTS: The delivered median dose intensity
      was 99% (interquartile range = 96%-100%) for the standard arm and 182%
      (interquartile range = 163%-196%) for the dose-dense arm. After a median follow
      up of 14 months, overall response to treatment was observed in 118 (80%) of the
      148 evaluable patients in the standard arm and in 129 (88%) of the 147 evaluable
      patients in the dose-dense arm, a statistically non-significant difference.
      Median overall survival was 13.9 months (95% confidence interval [CI] = 12.9 to
      15.8 months) in the standard arm and 14.4 months (95% CI = 12.7 to 16.0) in the
      dose-dense arm, and the 2-year survival was 22% (95% CI = 16% to 29%) and 19%
      (95% CI = 14% to 27%), respectively--neither difference being statistically
      significant. The median treatment free time was 286 days (95% CI = 229 to 343
      days) for the standard arm and 367 days (95% CI = 321 to 413 days) for the dose
      dense arm (difference = 81 days; P = .109). Statistically significantly more
      hematologic toxicity was reported in the dose-dense arm than in the standard arm,
      but the number of cycles complicated by neutropenic sepsis was statistically
      significantly higher in the standard arm than in the dose-dense arm (15.3% versus
      11.6%, respectively; difference = 3.7%, 95% CI = -4.1% to 11.5%; P = .03).
      CONCLUSIONS: Dose-dense ICE chemotherapy for SCLC led to shorter treatment
      duration and less neutropenic sepsis than did standard ICE but did not improve
      overall survival.

PMID- 15870438
TI  - Cervical cancer in women with comprehensive health care access: attributable
      factors in the screening process.
AB  - BACKGROUND: Invasive cervical cancer is highly preventable, yet it continues to
      occur, even among women who have access to cancer screening and treatment
      services. To reduce cervical cancer among such women, reasons for its occurrence
      must be better understood. We examined factors associated with the diagnosis of
      cervical cancer among women enrolled in health plans. METHODS: We identified all
      cases of invasive cervical cancer (n = 833) diagnosed from January 1, 1995,
      through December 31, 2000, among women who were long-term members of seven
      prepaid comprehensive health plans and reviewed each woman's medical records for
      the 3 years prior to her cancer diagnosis. Women were classified into one of
      three categories based on Pap test histories 4-36 months before diagnosis:
      failure to screen with a Pap test, failure in detection by a Pap test, or failure
      in follow-up of an abnormal test result. RESULTS: The majority of cases (n = 464;
      56%) were in women who had no Pap tests during the period 4-36 months prior to
      diagnosis. Of the remaining cases, 263 (32%) were attributed to Pap test
      detection failure and 106 (13%) to follow-up failure. Being older (odds ratio
      [OR] = 6.48, 95% confidence interval [CI] = 3.89 to 10.79) or living in an area
      of higher poverty (OR = 1.72, 95% CI = 1.11 to 2.67) or having a lower education
      level (OR= 1.52; 95% CI = 1.07 to 2.16) was associated with the likelihood of
      being assigned to the failure to screen category versus either of the other two
      categories. A total of 375 (81%) of the 464 patients who had not had Pap
      screening had had at least one outpatient visit 4-36 months prior to cancer
      diagnosis. The cancer diagnostic process was triggered by a routine screening
      examination in 44% of patients, whereas 53% of the patients presented with
      symptoms consistent with cervical cancer; the remaining 3% were identified
      fortuitously during the course of receiving noncervical care. CONCLUSIONS: To
      reduce the incidence of invasive cervical cancer among women with access to
      screening and treatment, Pap screening adherence should be increased. In
      addition, strategies to improve the accuracy of Pap screening could afford
      earlier detection of cervical cancer.

PMID- 15870439
TI  - Plasma vitamin B6 and the risk of colorectal cancer and adenoma in women.
AB  - BACKGROUND: Vitamin B6, whose main circulating form is pyridoxal 5'-phosphate
      (PLP), is important in one-carbon metabolism, which is critical for DNA synthesis
      and DNA methylation, both of which are potentially involved in colorectal
      carcinogenesis. However, no previous epidemiologic studies have directly
      evaluated the association of plasma PLP with risk for colorectal neoplasia.
      METHODS: We conducted a prospective nested case-control study of 32,826 female
      participants of the Nurses' Health Study who provided blood specimens in 1989
      1990. From 1989-1990 to 2000 (1998 for adenoma), a total of 194 incident
      colorectal cancer cases and 410 incident colorectal adenoma cases were identified
      from medical records. Multivariable-adjusted relative risks (RRs) and 95%
      confidence intervals (CIs) were calculated using logistic regression. All
      statistical tests were two-sided. RESULTS: A suggestive inverse association was
      observed between plasma PLP concentration and risk for colorectal cancer when
      comparing the highest quartile versus the lowest (RR = 0.56, 95% CI = 0.31 to
      1.01; P(trend) = .07); the association of PLP concentration with colon cancer was
      statistically significant (RR = 0.42, 95% CI = 0.21 to 0.85; P(trend) = .02).
      Both associations were statistically significant and stronger after controlling
      for intakes of folate, of multivitamins, and of methionine (for colorectal
      cancer, RR = 0.48, 95% CI = 0.25 to 0.92; P(trend) = .03; for colon cancer, RR =
      0.38, 95% CI = 0.18 to 0.80; P(trend) = .01). Total vitamin B(6) intake was also
      statistically significantly inversely associated with colon cancer risk (RR =
      0.51, 95% CI = 0.27 to 0.97; P(trend) = .007). There was a suggestive inverse
      association between plasma PLP concentration and advanced distal colorectal
      adenoma (RR = 0.65, 95% CI = 0.37 to 1.11; P(trend) = .08), but the association
      with early-stage adenoma was weaker (RR = 0.85, 95% CI = 0.52 to 1.38; P(trend) =
      .52). CONCLUSIONS: Our results suggest that vitamin B6 may be inversely
      associated with risk of colorectal neoplasia.

PMID- 15870440
TI  - Celebrity endorsements of cancer screening.
AB  - Celebrities often promote cancer screening by relating personal anecdotes about
      their own diagnosis or that of a loved one. We used data obtained from a random
      digit dialing survey conducted in the United States from December 2001 through
      July 2002 to examine the extent to which adults of screening age without a
      history of cancer had seen or heard or been influenced by celebrity endorsements
      of screening mammography, prostate-specific antigen (PSA) testing, or
      sigmoidoscopy or colonoscopy. The survey response rate was 72% among those known
      to be eligible and 51% among potentially eligible people accounting for those who
      could not be contacted. A total of 360 women aged 40 years or older and 140 men
      aged 50 years or older participated in the survey. Most respondents reported they
      "had seen or heard a celebrity talk about" mammography (73% of women aged 40
      years or older), PSA testing (63% of men aged 50 years or older), or
      sigmoidoscopy or colonoscopy (52% of adults aged 50 years or older). At least one
      fourth of respondents who had seen or heard a celebrity endorsement said that the
      endorsement made them more likely to undergo mammography (25%), PSA testing
      (31%), or sigmoidoscopy or colonoscopy (37%).

PMID- 15870441
TI  - Rotterdam randomized pilot studies of screening for prostate cancer--an overview
      after 10 years.

PMID- 15870442
TI  - Pseudomonas aeruginosa lectin LecB is located in the outer membrane and is
      involved in biofilm formation.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen which causes a variety of
      diseases, including respiratory tract infections in patients suffering from
      cystic fibrosis. Therapeutic treatment of P. aeruginosa infections is still very
      difficult because the bacteria exhibit high intrinsic resistance against a
      variety of different antibiotics and, in addition, form stable biofilms, e.g. in
      the human lung. Several virulence factors are produced by P. aeruginosa, among
      them the two lectins LecA and LecB, which exert different cytotoxic effects on
      respiratory epithelial cells and presumably facilitate bacterial adhesion to the
      airway mucosa. Here, the physiology has been studied of the lectin LecB, which
      binds specifically to L-fucose. A LecB-deficient P. aeruginosa mutant was shown
      to be impaired in biofilm formation when compared with the wild-type strain,
      suggesting an important role for LecB in this process. This result prompted an
      investigation of the subcellular localization of LecB by cell fractionation and
      subsequent immunoblotting. The results show that LecB is abundantly present in
      the bacterial outer-membrane fraction. It is further demonstrated that LecB could
      be released specifically by treatment of the outer-membrane fraction with p
      nitrophenyl alpha-L-fucose, whereas treatment with D-galactose had no effect. In
      contrast, a LecB protein carrying the mutation D104A, which results in a
      defective sugar-binding site, was no longer detectable in the membrane fraction,
      suggesting that LecB binds to specific carbohydrate ligands located at the
      bacterial cell surface. Staining of biofilm cells using fluorescently labelled
      LecB confirmed the presence of these ligands.

PMID- 15870444
TI  - Evidence of a charge-density threshold for optimum efficiency of biocidal
      cationic surfaces.
AB  - The deposition of organic monolayers containing quaternary ammonium groups has
      been shown by many authors to confer biocidal properties on a large variety of
      solid surfaces. In a search for the controlling factors, the authors have grafted
      quaternized poly(vinylpyridine) chains on glass surfaces by two different methods
      and varied the charge density within the organic layer between 10(12) and 10(16)
      positive charges per cm2. The measurements show that this parameter has a large
      influence on the killing efficiency. Bacterial death occurs in less than 10 min
      in the quiescent state above a threshold value. The value is smaller for bacteria
      in the growth state. It also depends on the bacterial type. An electrostatic
      mechanism based on the exchange of counterions between the functionalized
      cationic surface and the bacterial membrane is proposed and appears consistent
      with the results.

PMID- 15870443
TI  - Identity and effects of quorum-sensing inhibitors produced by Penicillium
      species.
AB  - Quorum sensing (QS) communication systems are thought to afford bacteria with a
      mechanism to strategically cause disease. One example is Pseudomonas aeruginosa,
      which infects immunocompromised individuals such as cystic fibrosis patients. The
      authors have previously documented that blockage of the QS systems not only
      attenuates Ps. aeruginosa but also renders biofilms highly susceptible to
      treatment with conventional antibiotics. Filamentous fungi produce a battery of
      secondary metabolites, some of which are already in clinical use as antimicrobial
      drugs. Fungi coexist with bacteria but lack active immune systems, so instead
      rely on chemical defence mechanisms. It was speculated that some of these
      secondary metabolites could interfere with bacterial QS communication. During a
      screening of 100 extracts from 50 Penicillium species, 33 were found to produce
      QS inhibitory (QSI) compounds. In two cases, patulin and penicillic acid were
      identified as being biologically active QSI compounds. Their effect on QS
      controlled gene expression in Ps. aeruginosa was verified by DNA microarray
      transcriptomics. Similar to previously investigated QSI compounds, patulin was
      found to enhance biofilm susceptibility to tobramycin treatment. Ps. aeruginosa
      has developed QS-dependent mechanisms that block development of the oxidative
      burst in PMN neutrophils. Accordingly, when the bacteria were treated with either
      patulin or penicillic acid, the neutrophils became activated. In a mouse
      pulmonary infection model, Ps. aeruginosa was more rapidly cleared from the mice
      that were treated with patulin compared with the placebo group.

PMID- 15870445
TI  - Characterization of the ERK homologue CpMK2 from the chestnut blight fungus
      Cryphonectria parasitica.
AB  - The Cryphonectria parasitica gene cpmk2, which encodes a mitogen-activated
      protein kinase belonging to the yeast extracellular signalling-regulated kinase
      (YERK1) subfamily, was isolated and its biological function was examined.
      Disruption of cpmk2 resulted in impaired pigmentation and abolished conidiation.
      Growth defects were observed in the cpmk2 mutant grown on solid plates, but
      growth of the mutant appeared normal in liquid media, including EP complete and
      PD broth, suggesting that the cpmk2 gene is involved in sensing and responding to
      growth conditions. The mutant's production of laccase, as measured by the size of
      the coloured area produced on tannic-acid-supplemented plates, was significantly
      reduced compared with the wild-type, but the intensity of the coloured area was
      unchanged, suggesting that the reduced laccase activity was owing to reduced
      growth on solid media rather than transcriptional downregulation. A dramatic
      reduction observed in the canker area produced by the cpmk2 mutant compared with
      the wild-type, even more severe than that of a hypovirulent strain, can also be
      ascribed to defective growth on solid surfaces rather than to impairments in a
      virulence factor(s). Downregulation of the pheromone gene Mf2/1 was also observed
      in the mutant, indicating a possible explanation for the regulation of the
      pheromone precursor gene in filamentous fungi and suggesting the presence of the
      yeast-like pheromone-responsive pathway in C. parasitica. Immunoblot analyses
      revealed that the phosphorylation level of CpMK2 increased in both virus-free and
      virus-containing strains in liquid cultures of up to 5 days old and decreased in
      older cultures. Moreover, the CpMK2 phosphorylation level increased in both
      strains after transfer from liquid to solid medium. However, levels of
      phosphorylated CpMK2 were similar in the two strains, suggesting that CpMK2,
      unlike CpMK1, is not under the direct control of a hypovirus.

PMID- 15870446
TI  - Ethambutol, a cell wall inhibitor of Mycobacterium tuberculosis, elicits L
      glutamate efflux of Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum is used for the large-scale production of L-glutamate,
      but the efflux of this amino acid is poorly understood. This study shows that
      addition of ethambutol (EMB) to growing cultures of C. glutamicum causes L
      glutamate efflux at rates of up to 15 nmol min(-1) (mg dry wt)(-1), whereas in
      the absence of EMB, no efflux occurs. EMB is used for the treatment of
      Mycobacterium tuberculosis, and at a molecular level it targets a series of
      arabinosyltransferases (EmbCAB). The single arabinosyltransferase-encoding emb
      gene of C. glutamicum was placed under the control of a Tet repressor (TetR).
      Experiments with this strain, as well as with an emb-overexpressing strain,
      coupled with biochemical analyses showed that: (i) emb expression was correlated
      with L-glutamate efflux, (ii) emb overexpression increased EMB resistance, (iii)
      EMB caused less arabinan deposition in cell wall arabinogalactan, and (iv) EMB
      caused a reduced content of cell-wall-bound mycolic acids. Thus EMB addition
      resulted in a marked disordering of the cell envelope, which was also discernible
      by examining cellular morphology. In order to further characterize the cellular
      response to EMB addition, genome-wide expression profiling was performed using
      DNA microarrays. This identified 76 differentially expressed genes, with 18 of
      them upregulated more than eightfold. Among these were the cell-wall-related
      genes ftsE and mepA (encoding a secreted metalloprotease); however, genes of
      central metabolism were largely absent. Given that an altered lipid composition
      of the plasma membrane of C. glutamicum can result in L-glutamate efflux, we
      speculate that major structural alterations of the cell envelope are transmitted
      to the membrane, which in turn activates an export system, perhaps via increased
      membrane tension.

PMID- 15870447
TI  - CAMP factor homologues in Propionibacterium acnes: a new protein family
      differentially expressed by types I and II.
AB  - Analysis of the draft genome sequence of the opportunistic pathogen
      Propionibacterium acnes type strain NCTC 737 (=ATCC 6919) revealed five genes
      with sequence identity to the co-haemolytic Christie-Atkins-Munch-Peterson (CAMP)
      factor of Streptococcus agalactiae. The predicted molecular masses for the
      expressed proteins ranged from 28 to 30 kDa. The genes were present in each of
      the three recently identified recA-based phylogenetic groupings of P. acnes (IA,
      IB and II), as assessed by PCR amplification. Conserved differences in CAMP
      factor gene sequences between these three groups were also consistent with their
      previous phylogenetic designations. All type IA, IB and II isolates were positive
      for the co-haemolytic reaction on sheep blood agar. Immunoblotting and silver
      staining of SDS-PAGE gels, however, revealed differential protein expression of
      CAMP factors amongst the different groups. Type IB and II isolates produced an
      abundance of CAMP factor 1, detectable by specific antibody labelling and silver
      staining of SDS-PAGE gels. In contrast, abundant CAMP factor production was
      lacking in type IA isolates, although larger amounts of CAMP factor 2 were
      detectable by immunoblotting compared with type II isolates. While the potential
      role of the abundant CAMP factor 1 in host colonization or virulence remains to
      be determined, it should be noted that the type strain of P. acnes used in much
      of the published literature is a type IA isolate and is, therefore, lacking in
      this attribute.

PMID- 15870448
TI  - Enterococcus faecalis divIVA: an essential gene involved in cell division, cell
      growth and chromosome segregation.
AB  - Enterococcus faecalis divIVA (divIVAEf) is an essential gene implicated in cell
      division and chromosome segregation. This gene was disrupted by insertional
      inactivation creating E. faecalis JHSR1, which was viable only when a wild-type
      copy of divIVAEf was expressed in trans, confirming the essentiality of the gene.
      The absence of DivIVAEf in E. faecalis JHSR1 inhibited proper cell division,
      which resulted in abnormal cell clusters possessing enlarged cells of altered
      shape instead of the characteristic diplococcal morphology of enterococci. The
      lower viability of the divIVAEf mutant is caused by improper nucleoid segregation
      and impaired septation within the numerous cells generated in each cluster.
      Overexpression of DivIVAEf in Escherichia coli KJB24 resulted in enlarged cells
      with disrupted cell division, suggesting that this round E. coli mutant strain
      could be used as an indicator for functionality of DivIVAEf. A Bacillus subtilis
      divIVA mutant was not complemented by DivIVAEf, indicating that this protein does
      not recognize DivIVA-specific target sites in B. subtilis, or that it does not
      interact with other proteins of the cell division machinery of this micro
      organism. DivIVAEf also failed to complement a Streptococcus pneumoniae divIVA
      mutant, supporting the phylogenetic distance between Enterococcus and
      Streptococcus. Our results indicate that DivIVA is a species-specific
      multifunctional protein implicated in cell division and chromosome segregation in
      E. faecalis.

PMID- 15870449
TI  - Mechanism of internalization of the cytolethal distending toxin of Actinobacillus
      actinomycetemcomitans.
AB  - Cytolethal distending toxin (CDT), which is encoded by three genes, cdtA, cdtB
      and cdtC, is now recognized to have a growing list of biological actions,
      including inhibition of cell cycle progression, promotion of apoptosis and
      stimulation of cytokine secretion. It appears that internalization of CDT is
      essential, at least for cell cycle blockade. Using purified recombinant CDT
      proteins from the periodontopathic bacterium Actinobacillus
      actinomycetemcomitans, the authors investigated which combination of toxin
      proteins produce cell cycle inhibition and which bound and/or entered into host
      cells. No evidence was found that CdtB bound to HEp-2 human epithelial cells. In
      contrast, both CdtA and CdtC bound to these cells. Induction of cell cycle arrest
      required that cells be exposed to both CdtB and CdtC. Pre-exposure of cells to
      CdtC for as little as 10 min, followed by removal of the free CdtC and addition
      of exogenous CdtB, resulted in the inhibition of cell cycle progression,
      suggesting that CdtB could bind to cell-surface-located CdtC. Using various
      methods to follow internalization of the CDT proteins it was concluded that CdtC
      acts to bind CdtB at the cell surface and transports it into the cell as a
      complex via an endosomal pathway blockable by monensin and brefeldin A.

PMID- 15870450
TI  - Role of RpoS and MutS in phase variation of Pseudomonas sp. PCL1171.
AB  - Pseudomonas sp. strain PCL1171 undergoes reversible colony phase variation
      between opaque phase I and translucent phase II colonies, which is dependent on
      spontaneous mutations in the regulatory genes gacA and gacS. Mutation of the mutS
      gene and constitutive expression of rpoS increases the frequency at which gac
      mutants appear 1000- and 10-fold, respectively. Experiments were designed to
      study the relationship between gacS, rpoS and mutS. These studies showed that (i)
      a functional gac system is required for the expression of rpoS, (ii) RpoS
      suppresses the expression of mutS and therefore increases the frequency of gac
      mutants, and (iii) upon mutation of rpoS and gacS, the expression of mutS is
      increased. Mutation of gacS abolishes suppression of mutS expression in
      stationary growth, suggesting that additional gac-dependent factors are involved
      in this suppression. In conclusion, inefficient mutation repair via MutS, of
      which the expression is influenced by gacA/S itself and by rpoS in combination
      with other factors, contributes to the high frequency of mutations accumulating
      in gacA/S. The role of RpoS in the growth advantage of a gac mutant was analysed,
      and mutation of rpoS only reduced the length of the lag phase, but did not affect
      the growth rate, suggesting a role for both RpoS and a reduction of metabolic
      load in the growth advantage of a gac mutant.

PMID- 15870451
TI  - Allosteric NADP-glutamate dehydrogenase from aspergilli: purification,
      characterization and implications for metabolic regulation at the carbon-nitrogen
      interface.
AB  - NADP-dependent glutamate dehydrogenase (NADP-GDH) mediates fungal ammonium
      assimilation through reductive synthesis of glutamate from 2-oxoglutarate. By
      virtue of its position at the interface of carbon and nitrogen metabolism,
      biosynthetic NADP-GDH is a potential candidate for metabolic control. In order to
      facilitate characterization, a new and effective dye-affinity method was devised
      to purify NADP-GDH from two aspergilli, Aspergillus niger and Aspergillus
      nidulans. The A. niger NADP-GDH was characterized at length and its kinetic
      interaction constants with glutamate (Km 34.7 mM) and ammonium (Km 1.05 mM; Ki
      0.4 mM) were consistent with an anabolic role. Isophthalate, 2-methyleneglutarate
      and 2,4-pyridinedicarboxylate were significant inhibitors, with respective Ki
      values of 6.9, 9.2 and 202.0 microM. The A. niger enzyme showed allosteric
      properties and a sigmoid response (nH=2.5) towards 2-oxoglutarate saturation. The
      co-operative behaviour was a feature common to NADP-GDH from Aspergillus awamori,
      A. nidulans and Aspergillus oryzae. NADP-GDH may therefore be a crucial
      determinant in adjusting 2-oxoglutarate flux between the tricarboxylic acid cycle
      and glutamate biosynthesis in aspergilli.

PMID- 15870452
TI  - The HiPIP from the acidophilic Acidithiobacillus ferrooxidans is correctly
      processed and translocated in Escherichia coli, in spite of the periplasm pH
      difference between these two micro-organisms.
AB  - The gene encoding a putative high-potential iron-sulfur protein (HiPIP) from the
      strictly acidophilic and chemolithoautotrophic Acidithiobacillus ferrooxidans
      ATCC 33020 has been cloned and sequenced. This potential HiPIP was overproduced
      in the periplasm of the neutrophile and heterotroph Escherichia coli. As shown by
      optical and EPR spectra and by electrochemical studies, the recombinant protein
      has all the biochemical properties of a HiPIP, indicating that the iron-sulfur
      cluster was correctly inserted. Translocation of this protein in the periplasm of
      E. coli was not detected in a DeltatatC mutant, indicating that it is dependent
      on the Tat system. The genetic organization of the iro locus in strains ATCC
      23270 and ATCC 33020 is different from that found in strains Fe-1 and BRGM.
      Indeed, in A. ferrooxidans ATCC 33020 and ATCC 23270 (the type strain), iro was
      not located downstream from purA but was instead downstream from petC2, encoding
      cytochrome c1 from the second A. ferrooxidans cytochrome bc1 complex. These
      findings underline the genotypic heterogeneity within the A. ferrooxidans
      species. The results suggest that Iro transfers electrons from a cytochrome bc1
      complex to a terminal oxidase, as proposed for the HiPIP in photosynthetic
      bacteria.

PMID- 15870454
TI  - Direct molecular mass determination of trehalose monomycolate from 11 species of
      mycobacteria by MALDI-TOF mass spectrometry.
AB  - Direct estimation of the molecular mass of single molecular species of trehalose
      6-monomycolate (TMM), a ubiquitous cell-wall component of mycobacteria, was
      performed by matrix-assisted laser desorption/ionization time-of-flight (MALDI
      TOF) mass spectrometry. When less than 1 microg TMM was analysed by MALDI-TOF
      mass spectrometry, quasimolecular ions [M+Na]+ of each molecular species were
      demonstrated and the numbers of carbons and double bonds (or cyclopropane rings)
      were determined. Since the introduction of oxygen atoms such as carbonyl, methoxy
      and ester groups yielded the appropriate shift of mass ions, the major subclasses
      of mycolic acid (alpha, methoxy, keto and wax ester) were identified without
      resorting to hydrolytic procedures. The results showed a marked difference in the
      molecular species composition of TMM among mycobacterial species. Unexpectedly,
      differing from other mycoloyl glycolipids, TMM from Mycobacterium tuberculosis
      showed a distinctive mass pattern, with abundant odd-carbon-numbered
      monocyclopropanoic (or monoenoic) alpha-mycolates besides dicyclopropanoic
      mycolate, ranging from C75 to C85, odd- and even-carbon-numbered methoxymycolates
      ranging from C83 to C94 and even- and odd-carbon-numbered ketomycolates ranging
      from C83 to C90. In contrast, TMM from Mycobacterium bovis (wild strain and BCG
      substrains) possessed even-carbon-numbered dicyclopropanoic alpha-mycolates. BCG
      Connaught strain lacked methoxymycolates almost completely. These results were
      confirmed by MALDI-TOF mass analysis of mycolic acid methyl esters liberated by
      alkaline hydrolysis and methylation of the original TMM. Wax ester-mycoloyl TMM
      molecular species were demonstrated for the first time as an intact form in the
      Mycobacterium avium-intracellulare group, M. phlei and M. flavescens. The M.
      avium-intracellulare group possessed predominantly C85 and C87 wax ester-mycoloyl
      TMM, while M. phlei and the rapid growers tested contained C80, C81, C82 and C83
      wax ester-mycoloyl TMM. This technique has marked advantages in the rapid
      analysis of not only intact glycolipid TMM, but also the mycolic acid composition
      of each mycobacterial species, since it does not require any degradation process.

PMID- 15870453
TI  - Biochemical and molecular characterization of an azoreductase from Staphylococcus
      aureus, a tetrameric NADPH-dependent flavoprotein.
AB  - Azo dyes are a predominant class of colourants used in tattooing, cosmetics,
      foods and consumer products. A gene encoding NADPH-flavin azoreductase (Azo1)
      from the skin bacterium Staphylococcus aureus ATCC 25923 was identified and
      overexpressed in Escherichia coli. RT-PCR results demonstrated that the azo1 gene
      was constitutively expressed at the mRNA level in S. aureus. Azo1 was found to be
      a tetramer with a native molecular mass of 85 kDa containing four non-covalently
      bound FMN. Azo1 requires NADPH, but not NADH, as an electron donor for its
      activity. The enzyme was resolved to dimeric apoprotein by removing the flavin
      prosthetic groups using hydrophobic-interaction chromatography. The dimeric
      apoprotein was reconstituted on-column and in free stage with FMN, resulting in
      the formation of a fully functional native-like tetrameric enzyme. The enzyme
      cleaved the model azo dye 2-[4-(dimethylamino)phenylazo]benzoic acid (Methyl Red)
      into N,N-dimethyl-p-phenylenediamine and 2-aminobenzoic acid. The apparent Km
      values for NADPH and Methyl Red substrates were 0.074 and 0.057 mM, respectively.
      The apparent Vmax was 0.4 microM min(-1) (mg protein)(-1). Azo1 was also able to
      metabolize Orange II, Amaranth, Ponceau BS and Ponceau S azo dyes. Azo1
      represents the first azoreductase to be identified and characterized from human
      skin microflora.

PMID- 15870455
TI  - Identification and preliminary characterization of cell-wall-anchored proteins of
      Staphylococcus epidermidis.
AB  - Staphylococcus epidermidis is a ubiquitous human skin commensal that has emerged
      as a major cause of foreign-body infections. Eleven genes encoding putative cell
      wall-anchored proteins were identified by computer analysis of the publicly
      available S. epidermidis unfinished genomic sequence. Four genes encode
      previously described proteins (Aap, Bhp, SdrF and SdrG), while the remaining
      seven have not been characterized. Analysis of primary sequences of the
      Staphylococcus epidermidis surface (Ses) proteins indicates that they have a
      structural organization similar to the previously described cell-wall-anchored
      proteins from S. aureus and other Gram-positive cocci. However, not all of the
      Ses proteins are direct homologues of the S. aureus proteins. Secondary and
      tertiary structure predictions suggest that most of the Ses proteins are composed
      of several contiguous subdomains, and that the majority of these predicted
      subdomains are folded into beta-rich structures. PCR analysis indicates that
      certain genes may be found more frequently in disease isolates compared to
      strains isolated from healthy skin. Patients recovering from S. epidermidis
      infections had higher antibody titres against some Ses proteins, implying that
      these proteins are expressed during human infection. Western blot analyses of
      early-logarithmic and late-stationary in vitro cultures suggest that different
      regulatory mechanisms control the expression of the Ses proteins.

PMID- 15870456
TI  - The dimorphic yeast Yarrowia lipolytica possesses an atypical
      phosphofructokinase: characterization of the enzyme and its encoding gene.
AB  - The phosphofructokinase from the non-conventional yeast Yarrowia lipolytica
      (YlPfk) was purified to homogeneity, and its encoding gene isolated. YlPfk is an
      octamer of 869 kDa composed of a single type of subunit, and shows atypical
      kinetic characteristics. It did not exhibit cooperative kinetics for fructose 6
      phosphate (Hill coefficient, h 1.1; S0.5 52 microM), it was inhibited moderately
      by MgATP (Ki 3.5 mM), and it was strongly inhibited by phosphoenolpyruvate (Ki 61
      microM). Fructose 2,6-bisphosphate did not activate the enzyme, and AMP and ADP
      were also without effect. The gene YlPFK1 has no introns, and encodes a putative
      protein of 953 aa, with a molecular mass consistent with the subunit size found
      after purification. Disruption of the gene abolished growth in glucose and Pfk
      activity, while reintroduction of the gene restored both properties. This
      indicates that Y. lipolytica has only one gene encoding Pfk, and supports the
      finding that the enzyme consists of identical subunits. Glucose did not interfere
      with growth of the Ylpfk1 disruptant in permissive carbon sources. The unusual
      kinetic characteristics of YlPfk, and the intracellular concentrations of
      glycolytic intermediates during growth in glucose, suggest that YlPfk may play an
      important role in the regulation of glucose metabolism in Y. lipolytica,
      different from the role played by the enzyme in Saccharomyces cerevisiae.

PMID- 15870457
TI  - Characterization of the interaction between subunits of the botulinum toxin
      complex produced by serotype D through tryptic susceptibility of the isolated
      components and complex forms.
AB  - The 650 kDa large toxin complex (L-TC) produced by Clostridium botulinum serotype
      D strain 4947 (D-4947) has a subunit structure composed of unnicked components,
      i.e. neurotoxin (NT), non-toxic non-haemagglutinin (NTNHA) and three
      haemagglutinin subcomponents (HA-70, HA-33 and HA-17). In this study, subunit
      interactions were investigated through the susceptibilities of the toxin
      components to limited trypsin proteolysis. Additionally, complex forms were
      reconstituted in vitro by various combinations of individual components. Trypsin
      treatment of intact D-4947 L-TC led to the formation of mature L-TC with nicks at
      specific sites of each component, which is usually observed in other strains of
      serotype D. NT, NTNHA and HA-17 were cleaved at their specific sites in either
      the single or complex forms, but HA-33 showed no sign of proteolysis. Unlike the
      other components, HA-70 was digested into random fragments as a single form, but
      it was cleaved into two fragments in the complex form. Based on the relative
      position of exposed or hidden regions of the individual components in the complex
      derived from their tryptic susceptibilities, an assembly model is proposed for
      the arrangement of individual subunits in the botulinum L-TC.

PMID- 15870458
TI  - Genetic analysis of Bacillus anthracis Sap S-layer protein crystallization
      domain.
AB  - Bacillus anthracis, the aetiological agent of anthrax, synthesizes two surface
      layer (S-layer) proteins. S-layers are two-dimensional crystalline arrays that
      completely cover bacteria. In rich medium, the B. anthracis S-layer consists of
      Sap during the exponential growth phase. Sap is a modular protein composed of an
      SLH (S-layer homology)-anchoring domain followed by a putative crystallization
      domain (Sap c). A projection map of the two-dimensional Sap array has been
      established on deflated bacteria. In this work, the authors used two approaches
      to investigate whether Sap c is the crystallization domain. The purified Sap c
      polypeptide (604 aa) was sufficient to form a crystalline structure, as
      illustrated by electron microscopy. Consistent with this result, the entire Sap c
      domain promoted auto-interaction in a bacterial two-hybrid screen developed for
      the present study. The screen was derived from a system that takes advantage of
      the Bordetella pertussis cyclase subdomain structure to enable one to identify
      peptides that interact. A screening strategy was then employed to study Sap c
      subdomains that mediate interaction. A random library, derived from the Sap c
      domain, was constructed and screened. The selected polypeptides interacting with
      the complete Sap c were all larger (155 aa and above) than the mean size of the
      randomly cloned peptides (approx. 60 residues). This result suggests that, in
      contrast with observations for other interactions studied with this two-hybrid
      system, large fragments were required to ensure efficient interaction. It was
      noteworthy that only one polypeptide, which spanned aa 148-358, was able to
      interact with less than the complete Sap c, in fact, with itself.

PMID- 15870459
TI  - Effect of carbon source on the cellulosomal subpopulations of Clostridium
      cellulovorans.
AB  - Clostridium cellulovorans produces a cellulase enzyme complex called the
      cellulosome. When cells were grown on different carbon substrates such as Avicel,
      pectin, xylan, or a mixture of all three, the subunit composition of the
      cellulosomal subpopulations and their enzymic activities varied significantly.
      Fractionation of the cellulosomes (7-11 fractions) indicated that the cellulosome
      population was heterogeneous, although the composition of the scaffolding protein
      CbpA, endoglucanase EngE and cellobiohydrolase ExgS was relatively constant. One
      of the cellulosomal fractions with the greatest endoglucanase activity also
      showed the highest or second highest cellulase activity under all growth
      conditions tested. The cellulosomal fractions produced from cells grown on a
      mixture of carbon substrates showed the greatest cellulase activity and contained
      CbpA, EngE/EngK, ExgS/EngH and EngL. High xylanase activity in cellulose, pectin
      and mixed carbon-grown cells was detected with a specific cellulosomal fraction
      which had relatively larger amounts of XynB, XynA and unknown proteins (35-45
      kDa). These results in toto indicate that the assembly of cellulosomes occurs in
      a non-random fashion.

PMID- 15870460
TI  - Overproduction, purification and characterization of FgaPT2, a
      dimethylallyltryptophan synthase from Aspergillus fumigatus.
AB  - A putative dimethylallyltryptophan synthase gene, fgaPT2, was identified in the
      genome sequence of Aspergillus fumigatus. fgaPT2 was cloned and overexpressed in
      Saccharomyces cerevisiae. The protein FgaPT2 was purified to near homogeneity and
      characterized biochemically. This enzyme was found to convert L-tryptophan to 4
      dimethylallyltryptophan, a reaction known to be the first step in ergot alkaloid
      biosynthesis. FgaPT2 is a soluble, dimeric protein with a subunit size of 52 kDa,
      and contains no putative prenyl diphosphate binding site (N/D)DXXD. Km values for
      L-tryptophan and dimethylallyl diphosphate (DMAPP) were determined as 8 and 4
      microM, respectively. Metal ions, such as Mg2+ and Ca2+, enhance the reaction
      velocity, but are not essential for the enzymic reaction. FgaPT2 showed a
      relatively strict substrate specificity for both tryptophan and DMAPP. FgaPT2 is
      the first enzyme in the biosynthesis of ergot alkaloids to be purified and
      characterized in homogeneous form after heterologous overproduction.

PMID- 15870461
TI  - Daptomycin biosynthesis in Streptomyces roseosporus: cloning and analysis of the
      gene cluster and revision of peptide stereochemistry.
AB  - Daptomycin is a 13 amino acid, cyclic lipopeptide produced by a non-ribosomal
      peptide synthetase (NRPS) mechanism in Streptomyces roseosporus. A 128 kb region
      of S. roseosporus DNA was cloned and verified by heterologous expression in
      Streptomyces lividans to contain the daptomycin biosynthetic gene cluster (dpt).
      The cloned region was completely sequenced and three genes (dptA, dptBC, dptD)
      encoding the three subunits of an NRPS were identified. The catalytic domains in
      the subunits, predicted to couple five, six or two amino acids, respectively,
      included a novel activation domain and amino-acid-binding pocket for
      incorporating the unusual amino acid l-kynurenine (Kyn), three types of
      condensation domains and an extra epimerase domain (E-domain) in the second
      module. Novel genes (dptE, dptF) whose products likely work in conjunction with a
      unique condensation domain to acylate the first amino acid, as well as other
      genes (dptI, dptJ) probably involved in supply of the non-proteinogenic amino
      acids l-3-methylglutamic acid and Kyn, were located next to the NRPS genes. The
      unexpected E-domain suggested that daptomycin would have d-Asn, rather than l
      Asn, as originally assigned, and this was confirmed by comparing stereospecific
      synthetic peptides and the natural product both chemically and microbiologically.

PMID- 15870462
TI  - Genetic identification of microcystin ecotypes in toxic cyanobacteria of the
      genus Planktothrix.
AB  - Microcystins (MCs) are toxic heptapeptides which are synthesized by the
      filamentous cyanobacterium Planktothrix and other genera via non-ribosomal
      peptide synthesis. MCs share the common structure cyclo(-D-ala1-L-X2-D-erythro
      beta-iso-aspartic acid3-L-Z4-adda5-D-Glu6-N-methyl-dehydroalanine7) [Adda; (2S,
      3S, 8S, 9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid], in
      which numerous MC variants have been reported. In general, the variation in
      structure is due to different amino acid residues in positions 7, 2 and 4 within
      the MC molecule, which are thought to be activated by the adenylation domains
      mcyAAd1, mcyBAd1 and mcyCAd, respectively. It was the aim of the study (i) to
      identify MC ecotypes that differed in the production of specific MC variants and
      (ii) to correlate the genetic variation within adenylation domains with the
      observed MC variants among 17 Planktothrix strains. Comparison of the sequences
      of mcyAAd1 revealed two distinctive Ad-genotypes differing in base pair
      composition and the insertion of an N-methyl transferase (NMT) domain. The
      mcyAAd1 genotype with NMT (2854 bp) correlated with N-methyl-dehydroalanine and
      the mcyAAd1 genotype without NMT (1692 bp) correlated with dehydrobutyrine in
      position 7. Within mcyBAd1, a lower genetic variation (0-4 %) and an exclusive
      correlation between one Ad-genotype and homotyrosine as well as another Ad
      genotype and arginine in position 2 was found. The sequences of mcyCAd were found
      to be highly similar (0-1 % dissimilarity) and all strains contained arginine in
      position 4. The results on adenylation domain polymorphism do provide insights
      into the evolutionary origin of adenylation domains in Planktothrix and may be
      combined with ecological research in order to provide clues about the abundance
      of genetically defined MC ecotypes in nature.

PMID- 15870463
TI  - Analysing protein-protein interactions of the Myxococcus xanthus Dif signalling
      pathway using the yeast two-hybrid system.
AB  - The dif operon is essential for fruiting body formation, fibril
      (exopolysaccharide) production and social motility of Myxococcus xanthus. The dif
      locus contains a gene cluster homologous to chemotaxis genes such as mcp (difA),
      cheW (difC), cheY (difD), cheA (difE) and cheC (difF), as well as an unknown ORF
      called difB. This study used yeast two-hybrid analysis to investigate possible
      interactions between Dif proteins, and determined that DifA, C, D and E interact
      in a similar fashion to chemotaxis proteins of Escherichia coli and Bacillus
      subtilis. It also showed that DifF interacted with DifD, and that the novel
      protein DifB did not interact with Dif proteins. Furthermore, DifA-F proteins
      were used to determine other possible protein-protein interactions in the M.
      xanthus genomic library. The authors not only confirmed the specific interactions
      among known Dif proteins, but also discovered two novel interactions between DifE
      and Nla19, and DifB and YidC, providing some new information about the Dif
      signalling pathway. Based on these findings, a model for the Dif signalling
      pathway is proposed.

PMID- 15870464
TI  - The dynamic behaviour of microtubules and their contributions to hyphal tip
      growth in Aspergillus nidulans.
AB  - Creating and maintaining cell polarity are complex processes that are not fully
      understood. Fungal hyphal tip growth is a highly polarized and dynamic process
      involving both F-actin and microtubules (MTs), but the behaviour and roles of the
      latter are unclear. To address this issue, MT dynamics and subunit distribution
      were analysed in a strain of Aspergillus nidulans expressing GFP-alpha-tubulin.
      Apical MTs are the most dynamic, the bulk of which move tipwards from multiple
      subapical spindle pole bodies, the only clear region of microtubule nucleation
      detected. MTs populate the apex predominantly by elongation at rates about three
      times faster than tip extension. This polymerization was facilitated by the
      tipward migration of MT subunits, which generated a tip-high gradient. Subapical
      regions of apical cells showed variable tubulin subunit distributions, without
      tipward flow, while subapical cells showed even tubulin subunit distribution and
      low MT dynamics. Short MTs, of a similar size to those reported in axons, also
      occasionally slid into the apex. During mitosis in apical cells, MT populations
      at the tip varied. Cells with less distance between the tip and the first nucleus
      were more likely to loose normal MT populations and dynamics. Reduced MTs in the
      tip, during mitosis or after exposure to the MT inhibitor carbendazim (MBC),
      generally correlated with reduced, but continuing growth and near-normal tip
      morphology. In contrast, the actin-disrupting agent latrunculin B reduced growth
      rates much more severely and dramatically distorted tip morphology. These results
      suggest substantial independence between MTs and hyphal tip growth and a more
      essential role for F-actin. Among MT-dependent processes possibly contributing to
      tip growth is the transportation of vesicles. However, preliminary
      ultrastructural data indicated a lack of direct MT-organelle interactions. It is
      suggested that the population of dynamic apical MTs enhance migration of the
      'cytomatrix', thus ensuring that organelles and proteins maintain proximity to
      the constantly elongating tip.

PMID- 15870465
TI  - The rapid assignment of ruminal fungi to presumptive genera using ITS1 and ITS2
      RNA secondary structures to produce group-specific fingerprints.
AB  - Identification of microbial community members in complex environmental samples is
      time consuming and repetitive. Here, ribosomal sequences and hidden Markov models
      are used in a novel approach to rapidly assign fungi to their presumptive genera.
      The ITS1 and ITS2 fragments from a range of axenic, anaerobic gut fungal
      cultures, including several type strains, were isolated and the RNA secondary
      structures predicted for these sequences were used to generate a fingerprinting
      program. The methodology was then tested and the algorithms improved using a
      collection of environmentally derived sequences, providing a rapid indicator of
      the fungal diversity and numbers of novel sequence groups within the
      environmental sample from which they were derived. While the methodology was
      developed to assist in investigations involving the rumen ecosystem, it has
      potential generic application in studying diversity and population dynamics in
      other microbial ecosystems.

PMID- 15870466
TI  - Phenotypic differentiation and seeding dispersal in non-mucoid and mucoid
      Pseudomonas aeruginosa biofilms.
AB  - There is growing evidence that Pseudomonas aeruginosa biofilms exhibit a
      multicellular developmental life cycle analogous to that of the myxobacteria. In
      non-mucoid PAO1 biofilms cultured in glass flow cells the phenotypic
      differentiation of microcolonies into a motile phenotype in the interior of the
      microcolony and a non-motile surrounding 'wall phenotype' are described. After
      differentiation the interior cells coordinately evacuated the microcolony from
      local break out points and spread over the wall of the flow cell, suggesting that
      the specialized microcolonies were analogous to crude fruiting bodies. A
      microcolony diameter of approximately 80 microm was required for differentiation,
      suggesting that regulation was related to cell density and mass transfer
      conditions. This phenomenon was termed 'seeding dispersal' to differentiate it
      from 'erosion' which is the passive removal of single cells by fluid shear. Using
      the flow cell culturing method, in which reproducible seeding phenotype in PAO1
      wild-type was demonstrated, the effects of quorum sensing (QS) and rhamnolipid
      production (factors previously identified as important in determining biofilm
      structure) on seeding dispersal using knockout mutants isogenic with PAO1 was
      investigated. Rhamnolipid (rhlA) was not required for seeding dispersal but
      las/rhl QS (PAO1-JP2) was, in our system. To assess the clinical relevance of
      these data, mucoid P. aeruginosa cystic fibrosis isolate FRD1 was also
      investigated and was seeding-dispersal-negative.

PMID- 15870467
TI  - Cationic antimicrobial peptides elicit a complex stress response in Bacillus
      subtilis that involves ECF-type sigma factors and two-component signal
      transduction systems.
AB  - Stress responses of Bacillus subtilis to membrane-active cationic antimicrobial
      peptides were studied. Global analysis of gene expression by DNA macroarray
      showed that peptides at a subinhibitory concentration activated numerous genes. A
      prominent pattern was the activation of two extracytoplasmic function sigma
      factor regulons, SigW and SigM. Two natural antimicrobial peptides, LL-37 and PG
      1, were weak activators of SigW regulon genes, whereas their synthetic analogue
      poly-L-lysine was clearly a stronger activator of SigW. It was demonstrated for
      the first time that LL-37 is a strong and specific activator of the YxdJK two
      component systems, one of the three highly homologous two-component systems
      sensing antimicrobial compounds. YxdJK regulates the expression of the YxdLM ABC
      transporter. The LiaRS (YvqCE) TCS was also strongly activated by LL-37, but its
      activation is not LL-37 specific, as was demonstrated by its activation with PG-1
      and Triton X-100. Other strongly LL-37-induced genes included yrhH and yhcGHI.
      Taken together, the responses to cationic antimicrobial peptides revealed highly
      complex regulatory patterns and induction of several signal transduction
      pathways. The results suggest significant overlap between different stress
      regulons and interdependence of signal transduction pathways mediating stress
      responses.

PMID- 15870468
TI  - The Ess1 prolyl isomerase is dispensable for growth but required for virulence in
      Cryptococcus neoformans.
AB  - Cryptococcus neoformans is an important human fungal pathogen that also serves as
      a model for studies of fungal pathogenesis. C. neoformans contains several genes
      encoding peptidyl-prolyl cis/trans isomerases (PPIases), enzymes that catalyse
      changes in the folding and conformation of target proteins. Three distinct
      classes of PPIases have been identified: cyclophilins, FK506-binding proteins
      (FKBPs) and parvulins. This paper reports the cloning and characterization of
      ESS1, which is believed to be the first (and probably only) parvulin-class PPIase
      in C. neoformans. It is shown that ESS1 from C. neoformans is structurally and
      functionally homologous to ESS1 from Saccharomyces cerevisiae, which encodes an
      essential PPIase that interacts with RNA polymerase II and plays a role in
      transcription. In C. neoformans, ESS1 was found to be dispensable for growth,
      haploid fruiting and capsule formation. However, ESS1 was required for virulence
      in a murine model of cryptococcosis. Loss of virulence might have been due to the
      defects in melanin and urease production observed in ess1 mutants, or to defects
      in transcription of as-yet-unidentified virulence genes. The fact that Ess1 is
      not essential in C. neoformans suggests that, in this organism, some of its
      functions might be subsumed by other prolyl isomerases, in particular,
      cyclophilins Cpa1 or Cpa2. This is supported by the finding that ess1 mutants
      were hypersensitive to cyclosporin A. C. neoformans might therefore be a useful
      organism in which to investigate crosstalk among different families of prolyl
      isomerases.

PMID- 15870469
TI  - Roles of Brucella abortus SpoT in morphological differentiation and
      intramacrophagic replication.
AB  - The essential mechanisms and virulence factors enabling Brucella species to
      survive and replicate inside host macrophages are not fully understood. The
      authors previously reported that a putative guanosine 5'-diphosphate 3'
      diphosphate (ppGpp) mutant (spoT mutant) of Brucella abortus failed to replicate
      in HeLa cells. The present study showed that the pattern of surface proteins and
      morphological change of the spoT mutant were different from B. abortus wild-type.
      B. abortus wild-type changed its morphology upon treatment with ppGpp synthetase
      I activation inhibitor. In various tests under stress conditions, including
      nutrient starvation, nitric oxide resistance, acid resistance and antibiotic
      resistance, the spoT mutant had a lower stress resistance than B. abortus wild
      type. Although the spoT mutant has the same smooth phenotype and LPS profile as
      B. abortus wild-type, it had a higher rate of adherence to macrophages but lower
      internalization and intracellular replication within macrophages. The spoT mutant
      did not co-localize with either late endosomes or lysosomes and was almost
      cleared from the spleens of mice after 10 days, without splenomegaly. RT-PCR was
      used to detect spoT mRNA from around 10(6) cells incubated in low-pH enriched
      medium; it showed that the expression of spoT increased after 30 min incubation.
      The data suggest that SpoT does not contribute to intracellular trafficking of B.
      abortus, but contributes to the maintenance of bacterial morphology and the
      physiological adaptation required for intracellular replication.

PMID- 15870470
TI  - Analysis of the Candida albicans Als2p and Als4p adhesins suggests the potential
      for compensatory function within the Als family.
AB  - The ALS (agglutinin-like sequence) gene family encodes eight large cell-surface
      glycoproteins. The work presented here focuses on Als2p and Als4p, and is part of
      a larger effort to deduce the function of each Als protein. Both ALS4 alleles
      were deleted from the Candida albicans genome and the phenotype of the mutant
      strain (als4Delta/als4Delta; named 2034) studied. Loss of Als4p slowed germ tube
      formation of cells grown in RPMI 1640 medium and resulted in decreased adhesion
      of C. albicans to vascular endothelial cells. Loss of Als4p did not affect
      adhesion to buccal epithelial cells, biofilm formation in a catheter model, or
      adhesion to or destruction of oral reconstituted human epithelium (RHE). Although
      deletion of one ALS2 allele was achieved readily, a strain lacking the second
      allele was not identified despite screening thousands of transformants. The
      remaining ALS2 allele was placed under control of the C. albicans MAL2 promoter
      to create an als2Delta/PMAL2-ALS2 strain (named 2342). Real-time RT-PCR analysis
      of strain 2342 grown in glucose-containing medium (non-inducing conditions)
      showed that although ALS2 transcript levels were greatly reduced compared to wild
      type cells, some ALS2 transcript remained. The decreased ALS2 expression levels
      were sufficient to slow germ tube formation in RPMI 1640 and Lee medium, reduce
      adhesion to vascular endothelial cells and to RHE, decrease RHE destruction, and
      impair biofilm formation. Growth of strain 2342 in maltose-containing medium
      (inducing conditions) restored the wild-type phenotype in all assays. Real-time
      RT-PCR analysis demonstrated that in maltose-containing medium, strain 2342
      overexpressed ALS2 compared to wild-type cells; however no overexpression
      phenotype was apparent. Microarray analysis revealed little transcriptional
      response to ALS4 deletion, but showed twofold up-regulation of orf19.4765 in the
      glucose-medium-grown als2Delta/PMAL2-ALS2 strain. orf19.4765 encodes a protein
      with features of a glycosylated cell wall protein with similarity to
      Saccharomyces cerevisiae Ccw12p, although initial analysis suggested functional
      differences between the two proteins. Real-time RT-PCR measurement of ALS2 and
      ALS4 transcript copy number showed a 2.8-fold increase in ALS2 expression in the
      als4Delta/als4Delta strain and a 3.2-fold increase in ALS4 expression in the
      als2Delta/PMAL2-ALS2 strain, suggesting the potential for compensatory function
      between these related proteins.

PMID- 15870471
TI  - Yeast wall protein 1 of Candida albicans.
AB  - Yeast wall protein 1 (Ywp1, also called Pga24) of Candida albicans is predicted
      to be a 533 aa polypeptide with an N-terminal secretion signal, a C-terminal
      glycosylphosphatidylinositol anchor signal and a central region rich in serine
      and threonine. In yeast cultures, Ywp1p appeared to be linked covalently to
      glucans of the wall matrix, but, as cultures approached stationary phase, Ywp1p
      accumulated in the medium and was extractable from cells with disulfide-reducing
      agents. An 11 kDa propeptide of Ywp1p was also present in these soluble
      fractions; it possessed the sole N-glycan of Ywp1p and served as a useful marker
      for Ywp1p. DNA vaccines encoding all or part of Ywp1p generated analytically
      useful antisera in mice, but did not increase survival times for disseminated
      candidiasis. Replacement of the coding sequence of YWP1 with the fluorescent
      reporter GFP revealed that expression of YWP1 is greatest during yeast
      exponential-phase growth, but downregulated in stationary phase and upon
      filamentation. Expression was upregulated when the extracellular phosphate
      concentration was low. Disruption by homologous recombination of both YWP1
      alleles resulted in no obvious change in growth, morphology or virulence, but the
      Ywp1p-deficient blastoconidia exhibited increased adhesiveness and biofilm
      formation, suggesting that Ywp1p may promote dispersal of yeast forms of C.
      albicans.

PMID- 15870472
TI  - The putative vacuolar ATPase subunit Vma7p of Candida albicans is involved in
      vacuole acidification, hyphal development and virulence.
AB  - The vacuolar H+-ATPase (V-ATPase) component Vma7p of the human-pathogenic yeast
      Candida albicans regulates hyphal growth induced by serum and Spider medium and
      is essential for virulence. In order to characterize the functions of the
      putative V-ATPase subunit Vma7p of C. albicans, null mutants were generated. The
      resulting mutants showed reduced vacuole acidification, which correlated with
      defective growth at alkaline pH. In addition, defects in degradation of
      intravacuolar putative endosomal structures were observed. vma7 null mutants were
      sensitive towards the presence of metal ions. It is concluded that the
      sequestration of toxic ions in the vacuole via a H+ gradient generated by the V
      ATPase is affected. The vma7 null mutant strains were avirulent in a mouse model
      of systemic candidiasis. In addition, C. albicans vma7 null mutants and the null
      mutant strain of the Vma7p-interacting phosphatidylinositol 3-kinase Vps34p
      showed similar phenotypes. In summary, the V-ATPase subunit Vma7p is involved in
      vacuolar ion transport and this transport is required for hyphal growth and
      virulence of C. albicans.

PMID- 15870473
TI  - Prolonged selection in aerobic, glucose-limited chemostat cultures of
      Saccharomyces cerevisiae causes a partial loss of glycolytic capacity.
AB  - Prolonged cultivation of Saccharomyces cerevisiae in aerobic, glucose-limited
      chemostat cultures (dilution rate, 0.10 h(-1)) resulted in a progressive decrease
      of the residual glucose concentration (from 20 to 8 mg l(-1) after 200
      generations). This increase in the affinity for glucose was accompanied by a
      fivefold decrease of fermentative capacity, and changes in cellular morphology.
      These phenotypic changes were retained when single-cell isolates from prolonged
      cultures were used to inoculate fresh chemostat cultures, indicating that genetic
      changes were involved. Kinetic analysis of glucose transport in an 'evolved'
      strain revealed a decreased Km, while Vmax was slightly increased relative to the
      parental strain. Apparently, fermentative capacity in the evolved strain was not
      controlled by glucose uptake. Instead, enzyme assays in cell extracts of the
      evolved strain revealed strongly decreased capacities of enzymes in the lower
      part of glycolysis. This decrease was corroborated by genome-wide transcriptome
      analysis using DNA microarrays. In aerobic batch cultures on 20 g glucose l(-1),
      the specific growth rate of the evolved strain was lower than that of the
      parental strain (0.28 and 0.37 h(-1), respectively). Instead of the
      characteristic instantaneous production of ethanol that is observed when aerobic,
      glucose-limited cultures of wild-type S. cerevisiae are exposed to excess
      glucose, the evolved strain exhibited a delay of approximately 90 min before
      aerobic ethanol formation set in. This study demonstrates that the effects of
      selection in glucose-limited chemostat cultures extend beyond glucose-transport
      kinetics. Although extensive physiological analysis offered insight into the
      underlying cellular processes, the evolutionary 'driving force' for several of
      the observed changes remains to be elucidated.

PMID- 15870474
TI  - mrpA, a gene with roles in resistance to Na+ and adaptation to alkaline pH in the
      cyanobacterium Anabaena sp. PCC7120.
AB  - Transposon mutagenesis of Anabaena sp. PCC7120 led to the isolation of a mutant
      strain, PHB11, which grew poorly at pH values above 10. The mutant strain
      exhibited pronounced Na+ sensitivity; this sensitivity was higher under basic
      conditions. Mutant PHB11 also showed an inhibition of photosynthesis that was
      much more pronounced at alkaline pH. Reconstruction of the transposon mutation of
      PHB11 in the wild-type strain reproduced the phenotype of the original mutant.
      The wild-type version of the mutated gene was cloned and the mutation
      complemented. In mutant strain PHB11, the transposon had inserted within an ORF
      that is part of a seven-ORF operon with significant sequence similarity to a
      family of bacterial operons that are believed to code for a novel multiprotein
      cation/proton antiporter primarily involved in resistance to salt stress and
      adaptation to alkaline pH. The Anabaena operon was denoted mrp (multiple
      resistance and pH adaptation) following the nomenclature of the Bacillus subtilis
      operon; the ORF mutated in PHB11 corresponded to mrpA. Computer analysis
      suggested that all seven predicted Anabaena Mrp proteins were highly hydrophobic
      with several transmembrane domains; in fact, the predicted protein sequences
      encoded by mrpA, mrpB and mrpC showed significant similarity to hydrophobic
      subunits of the proton pumping NADH : ubiquinone oxidoreductase. In vivo
      expression studies indicated that mrpA is induced with increasing external Na+
      concentrations and alkaline pH; mrpA is also upregulated under inorganic carbon
      (Ci) limitation. The biological significance of a putative cyanobacterial Mrp
      complex is discussed.

PMID- 15870475
TI  - Deletion of the yiaMNO transporter genes affects the growth characteristics of
      Escherichia coli K-12.
AB  - Binding-protein-dependent secondary transporters make up a unique transport
      protein family. They use a solute-binding protein in proton-motive-force-driven
      transport. Only a few systems have been functionally analysed. The yiaMNO genes
      of Escherichia coli K-12 encode one family member that transports the rare
      pentose l-xylulose. Its physiological role is unknown, since wild-type E. coli K
      12 does not utilize l-xylulose as sole carbon source. Deletion of the yiaMNO
      genes in E. coli K-12 strain MC4100 resulted in remarkable changes in the
      transition from exponential growth to the stationary phase, high-salt survival
      and biofilm formation.

PMID- 15870476
TI  - Secondary metabolites from endophytic Streptomyces aureofaciens CMUAc130 and
      their antifungal activity.
AB  - Streptomyces aureofaciens CMUAc130 was isolated from the root tissue of Zingiber
      officinale Rosc. (Zingiberaceae). It was an antagonist of Colletotrichum musae
      and Fusarium oxysporum, the causative agents of anthracnose of banana and wilt of
      wheat, respectively. Evidence for the in vitro antibiosis of S. aureofaciens
      CMUAc130 was demonstrated by the zone of fungal-growth inhibition. Microscopic
      observations showed thickness and bulbous structures at the edges of the
      inhibited fungal hyphae. The culture filtrate and crude extract from this strain
      were all inhibitory to tested phytopathogenic fungi. The major active ingredients
      from the culture filtrate of S. aureofaciens CMUAc130 were purified by silica gel
      column chromatography and identified to be (i) 5,7-dimethoxy-4-p
      methoxylphenylcoumarin and (ii) 5,7-dimethoxy-4-phenylcoumarin by NMR and mass
      spectral data, respectively. Bioassay studies showed that compounds (i) and (ii)
      had antifungal activities against tested fungi, and their MICs were found to be
      120 and 150 microg ml(-1), respectively. This is the first report of compounds
      (i) and (ii) from micro-organisms as active ingredients for the control of
      phytopathogenic fungi.

PMID- 15870477
TI  - Hydrogen concentrations in methane-forming cells probed by the ratios of reduced
      and oxidized coenzyme F420.
AB  - Coenzyme F420 is the central low-redox-potential electron carrier in methanogenic
      metabolism. The coenzyme is reduced under hydrogen by the action of F420
      dependent hydrogenase. The standard free-energy change at pH 7 of F420 reduction
      was determined to be -15 kJ mol(-1), irrespective of the temperature (25-65
      degrees C). Experiments performed with methane-forming cell suspensions of
      Methanothermobacter thermautotrophicus incubated under various conditions
      demonstrated that the ratios of reduced and oxidized F420 were in thermodynamic
      equilibrium with the gas-phase hydrogen partial pressures. During growth in a fed
      batch fermenter, ratios changed in connection with the decrease in dissolved
      hydrogen. For most of the time, the changes were as expected for thermodynamic
      equilibrium between the oxidation state of F420 inside the cells and
      extracellular hydrogen. Also, methanol-metabolizing, but not acetate-converting,
      cells of Methanosarcina barkeri maintained the ratios of reduced and oxidized
      coenzyme F420 in thermodynamic equilibrium with external hydrogen. The results of
      the study demonstrate that F420 is a useful probe to assess in situ hydrogen
      concentrations in H2-metabolizing methanogens.

PMID- 15870478
TI  - SoxRS-mediated regulation of chemotrophic sulfur oxidation in Paracoccus
      pantotrophus.
AB  - Paracoccus pantotrophus GB17 requires thiosulfate for induction of the sulfur
      oxidizing (Sox) enzyme system. The soxRS genes are divergently oriented to the
      soxVWXYZA-H genes. soxR predicts a transcriptional regulator of the ArsR family
      and soxS a periplasmic thioredoxin. The homogenate mutant GBOmegaS carrying a
      disruption of soxS by the Omega-kanamycin-resistance-encoding interposon
      expressed a low thiosulfate-oxidizing activity under heterotrophic and
      mixotrophic growth conditions. This activity was repressed by complementation
      with soxR, suggesting that SoxR acts as a repressor and SoxS is essential for
      full expression. Sequence analysis uncovered operator characteristics in the
      intergenic regions soxS-soxV and soxW-soxX. In each region a transcription start
      site was identified by primer extension analysis. Both regions were cloned into
      the vector pRI1 and transferred to P. pantotrophus. Strains harbouring pRI1 with
      soxS-soxV or soxW-soxX expressed the sox genes under heterotrophic conditions at
      a low rate, indicating repressor titration. Sequence analysis of SoxR suggested a
      helix-turn-helix (HTH) motif at position 87-108 and uncovered an invariant Cys-80
      and a cysteine residue at the C-terminus. SoxR was overproduced in Escherichia
      coli with an N-terminal His6-tag and purified to near homogeneity.
      Electrophoretic gel mobility shift assays with SoxR retarded the soxS-soxV region
      as a single band while the soxW-soxX region revealed at least two protein-DNA
      complexes. These data demonstrated binding of SoxR to the relevant DNA. This is
      believed to be the first report of regulation of chemotrophic sulfur oxidation at
      the molecular level.

PMID- 15870479
TI  - Pleiotropic effect of the SCO2127 gene on the glucose uptake, glucose kinase
      activity and carbon catabolite repression in Streptomyces peucetius var. caesius.
AB  - SCO2127 and SCO2126 (glkA) are adjacent regions located in Streptomyces
      coelicolor DNA. glkA encodes glucose kinase (Glk), which has been implicated in
      carbon catabolite repression (CCR) in the genus Streptomyces. In this work, the
      glkA and SCO2127 genes from S. coelicolor were used, either individually or
      together, to transform three mutants of Streptomyces peucetius var. caesius
      resistant to CCR. These mutants present decreased levels of Glk, and deficiency
      in glucose transport. When the mutants were transformed with a plasmid containing
      the SCO2127 sequence, glucose uptake and Glk activity values were increased to
      levels similar to or higher than those of the original strain, and each strain
      regained sensitivity to CCR. This result was surprising considering that the
      putative SCO2127 amino acid sequence does not seem to encode a glucose permease
      or a Glk. In agreement with these results, an increase in glkA mRNA levels was
      observed in a CCR-resistant mutant transformed with SCO2127 compared with those
      of the original strain and the CCR-resistant mutant itself. As expected,
      recombinants containing the glkA sequence reverted Glk to normal activity values,
      but glucose uptake remained deficient. The data suggest that the SCO2127 gene
      product enhances transcription of both genes, and support the first specific role
      for this region in Streptomyces species. The physiological consequence of this
      effect is an increase in the glucose catabolites that may be involved in
      eliciting CCR in this genus.

PMID- 15870481
TI  - Variation in outpatient mental health service utilization under capitation.
AB  - BACKGROUND: To improve the financing of Colorado's public mental health system,
      the state designed, implemented, and evaluated a pilot program that consisted of
      three reimbursement models for the provision of outpatient services. Community
      mental health centers (CMHCs), the primary providers of comprehensive mental
      health services to Medicaid recipients in Colorado, had to search for innovative
      ways to provide cost-effective services. STUDY AIMS: This study assessed
      outpatient service delivery to Medicaid-eligible consumers under this program.
      This paper is among the first to study variations in the delivery of specific
      types of outpatient mental health services under capitated financing systems.
      METHODS: This study uses claims data (1994-1997) from Colorado's Medicaid and
      Mental Health Services Agency. The fee-for-service (FFS) model served as the
      comparison model. Two capitated models under evaluation are: (i) direct
      capitation (DC), where the state contracts with a non-profit entity to provide
      both the services and administers the capitated financing, and (ii) managed
      behavioral health organization (MBHO), which is a joint venture between a for
      profit company who manages the capitated financing and a number of non-profit
      entities who deliver the services. A sample of severely mentally ill patients who
      reported at least one inpatient visit was included in the analysis. Types of
      outpatient services of interest are: day-treatment visits, group therapy,
      individual therapy, medication monitoring, case management, testing, and all
      other services. Comparisons were set up to examine differences in service
      utilization and cost between FFS and each of the two capitated models, using a
      two-part model across three time periods. RESULTS: Results showed differences in
      service delivery among reimbursement models over time. Capitated providers had
      higher initial utilization in most outpatient service categories than their FFS
      counterparts and as a result of capitation, outpatient services delivered under
      these providers decreased to converge to the FFS pattern. Findings also suggest
      substitution between group therapy and individual psychotherapy. Overall, more
      service integration was observed and less complex service packages were provided
      post capitation. IMPLICATION FOR HEALTH CARE PROVISION AND POLICIES: Financing
      models and organizational arrangements have an impact on mental health service
      delivery. Changes in utilization and costs of specific types of outpatient
      services reflect the effects of capitation. Understanding the mechanism for these
      changes may lead to more streamlined service delivery allowing extra funding for
      expanding the range of cost-effective treatment alternatives. These changes pose
      implications for improving the financing of public mental health systems,
      coordination of mental health services with other healthcare and human services,
      and provision of services through a more efficient financing system.

PMID- 15870482
TI  - Variation in patient routine costliness in U.S. psychiatric facilities.
AB  - BACKGROUND: The Balanced Budget Refinement Act of 1999 included a Congressional
      mandate to develop a patient-level case mix prospective payment system (PPS) for
      all Medicare beneficiaries treated in PPS-exempt psychiatric facilities. Payment
      levels by case mix category have been proposed by the government based on claims
      and facility cost reports. Because of claims data limitations, these levels do
      not account for patient-specific staffing costs within a facility's routine
      units, nor are certain key patient characteristics considered for higher payment.
      AIMS OF THE STUDY: This study uses novel primary data to quantify heretofore
      unmeasured differences in daily staffing intensity on routine units among
      Medicare patients. The data are used to test for compression (or narrowing) in
      case mix payment weights that would result from using only Medicare claims and
      facility cost reports to quantify daily routine costliness. METHODS: Primary data
      on patient and staff times in over 20 activities were collected from 40
      psychiatric facilities and 66 psychiatric units, nation-wide. Patient times were
      reported on all inpatients on each shift over a 7-day study period. A resource
      intensity measure (in Registered Nurse (RN)-equivalent minutes) was constructed
      on a daily basis for 4,149 Medicare and 4,667 non-Medicare patient days. The
      routine measure is converted into daily cost using cost report per diems and
      ancillary costs added using submitted claims. Descriptive tables isolate key cost
      drivers for Medicare patients. Classification and Regression Trees (CART)
      clustering identifies 16 potential case mix groups. Multivariate regression is
      used to compare case mix, day-of-stay, and facility effects using 4 alternative
      measures of daily routine and ancillary costs. RESULTS: Patient daily routine
      intensity of care is found to vary by a factor of 3 or more between the top and
      bottom 10% of days. Medicare patient days were 12.5% more staff intensive than
      non-Medicare days, which may have been due to age and other differences. Older
      dementia and "residual diagnosis" patients are more intensive while schizophrenia
      and substance-related patients are less intensive. Age, psychiatric and medical
      severity, deficits in Activities in Daily Living (ADLs), dangerous behaviors, and
      electroconvulsive therapy (ECT) also contribute substantially to higher staffing
      intensity. Other patient characteristics were insignificant within broad
      diagnostic groups. Routine costs based on a single facility per diem produced
      narrower case mix cost differences--often by a factor of 2 or more--for 10 of 12
      groups with significantly higher costs. Adding patient-specific ancillary to
      uniform per diem costs only marginally decompressed costs. Day of-stay costs were
      similarly compressed when using only cost reports. DISCUSSION: Claims-based
      costing using Medicare cost reports unduly compresses (narrows) estimates of
      inter-group case mix cost differences. Also, by not capturing ADL deficits and
      dangerous behaviors, administrative data sets fail to identify small, but very
      resource intensive, patient groups. ECT treatment regimens, although rare,
      significantly increase costs on a daily basis. IMPLICATIONS FOR HEALTH POLICIES:
      Medicare's recently proposed prospective payment system for psychiatric
      inpatients uses claims-based costing methods based on widely available
      administrative data. Consequently, fewer high cost groups are identified due to
      non-reported patient characteristics such as ADL deficits. Moreover, inter-group
      relative cost differences are likely understated. It is also possible that any
      standardized dollar amount applied to group relative weights is understated
      because Medicare patients appear more intensive per day on routine units.
      IMPLICATIONS FOR FUTURE RESEARCH: Larger primary samples of special psychiatric
      units (e.g., med-psych, child/adolescent) could improve estimates of daily
      routine costliness. Larger samples could also support stronger tests of case mix
      and cost differences by facility type and teaching status. Medical records
      information on non-Medicare patients could quantify any systematic differences in
      average daily costs holding case mix constant. Similar primary studies of
      psychiatric patients treated outside PPS-exempt units in acute general hospitals
      could result in a fully integrated payment system for all mentally ill Medicare
      patients, thereby avoiding payment inefficiencies and inequities.

PMID- 15870483
TI  - Health status and access to care for children with special health care needs.
AB  - BACKGROUND: About 11-14% of children with special health care needs (CSHCN) have
      unmet needs during a given year. Little is known about the determinants of unmet
      health care needs for CSHCN. AIMS OF THE STUDY: The objective of this study was
      to explore the association between access to care (unmet needs) among CSHCN and
      their caregivers' mental health status as well as children's mental health
      status. METHODS: We surveyed a random sample of 1,088 caregivers of CSHCN who
      resided in the District of Columbia during the summer and fall of 2002. In the
      survey, we collected information on children's unmet needs mental health status
      (PARS) and their caregivers' mental health status (CES-D). We estimated the
      association between mental health status determinants of unmet needs adjusting
      for selection bias associated with plan choice (partially capitated managed care
      versus FFS) with an instrumental variables probit estimation technique. We used
      caregivers' preferences about physicians and hospitals networks, and whether the
      caregiver and child had the same last name to identify the plan choice equation.
      RESULTS: We found that caregivers with symptoms of depression were 26.3% more
      likely to report any unmet need, 67.6% more likely to report unmet hospital and
      physician need, 66.1% more likely to report unmet mental health care need and
      38.8% more likely to report unmet need for other health care services. Caregivers
      of children with poor psychological adjustment were 26.3% more likely to report
      their child had an unmet need and 92.3% more likely to report an unmet mental
      health care need. DISCUSSION: Our analyses show that children whose caregivers
      experience symptoms of depression are significantly more likely to encounter
      difficulties obtaining needed medical and mental health care services.
      Furthermore, the findings reported here indicate that children with poor
      psychological adjustment are significantly more likely to experience unmet needs
      for medical and mental health care services. Our study has some limitations.
      First, most of the children in our sample are African-American, so these findings
      may differ for children of other races. Second, these findings may not be
      applicable to CSHCN who reside in rural areas. Third, we recognize the
      possibility that child and caregiver mental health is potentially endogenous.
      IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The mental health status of CSHCN
      and their caregivers are barriers to care. IMPLICATIONS FOR HEALTH POLICIES:
      Policymakers should be concerned about the mental health status of children with
      special health care needs and their caregivers as such problems appear to be
      barriers to obtaining care. Therefore, to adequately address the access problems
      of children with special health care needs, policy must address the mental health
      problems of children and their caregivers. Providing mental health care for
      caregivers and children has the potential for improving overall access for CSHCN.
      IMPLICATION FOR FURTHER RESEARCH: Future research should determine the causal
      relationship between mental health problems of CSHCN and their caregivers and the
      level unmet health care needs.

PMID- 15870484
TI  - Implementation of social services for the chronically mentally ill in a Polish
      mental health district: consequences for service use and costs.
AB  - BACKGROUND: In accordance with the mental health reform in Poland, from 1970 to
      1980 the following mental health facilities were established within the general
      health system in the Warsaw District of Targowek: general hospital psychiatric
      ward, day hospital, outpatient clinic (OC), and community mobile team (CMT) with
      some procedures of assertive community treatment (ACT). In 1998 (according to the
      Mental Health Act of 1994), within the social welfare system, new community
      facilities were established in this district with psychosocial rehabilitation
      programs for the chronically mentally ill. These new social welfare facilities
      were a vocational rehabilitation center (VCR), community center of mutual help
      (CCOMH), and specialized social help services at client homes (SSHS). AIM OF THE
      STUDY: To determine the change of care delivered to chronic psychiatric patients
      in both the mental health and social welfare systems, and to compare the costs of
      care during two 2-year periods: before (Period A) and after (Period B) the 1998
      implementation of the new social welfare facilities in the Warsaw District of
      Targowek. METHODS: The sample consisted of 73 chronic psychiatric patients,
      admitted since 1998 to the new social welfare facilities. The authors evaluated
      and calculated the costs of the patients' use of mental health facilities during
      the two years before their first admission to VCR, CCOMH or SSHS in 1998 (Period
      A: 1996-1998) and their use of mental health and social welfare facilities during
      the two years after their admission to VCR, CCOMH or SSHS in 1998 (Period B: 1998
      2000). RESULTS: In this group of chronic patients, during Period B, the total
      duration of both full and partial hospitalizations decreased (-75.9% and -78.9%
      respectively), while the total number of outpatient mental health visits went up
      (+62.9%). In Period B the new social welfare facilities offered a substantial
      amount of day care and the global amount of supplied day care increased markedly.
      The total costs of the mental health system significantly decreased in Period B (
      65.7%), but new costs emerged in the social welfare system. Taken together, the
      total costs of care provided by the two systems in Period B were higher than the
      costs incurred by the mental health system alone in Period A (+33.9 %), but the
      increase in the total amount of services delivered was also relevant (+98.3%).
      The "out of pocket" expenses incurred by patients increased in Period B (+13.9%).
      DISCUSSION: The activity of the new social welfare facilities (VRC, CCOMH, SSHS)
      seems to reduce both full time and partial hospitalizations. Despite the
      increasing costs of medication reimbursement, and the increased use of CMT and
      OC, the overall costs for the mental health system were substantially reduced.
      The decrease in day hospital use is probably due to the large amount of daily
      social support and home services offered in VRC, CCOMH and SSHS. The results
      emphasize the importance of evaluating the coordination of care for chronically
      mentally ill patients in the mental health and social welfare systems.

PMID- 15870485
TI  - Intensive treatment and stem cell transplantation in chronic myelogenous
      leukemia: long-term follow-up.
AB  - In the present study we combined interferon (IFN) and hydroxyurea (HU) treatment,
      intensive chemotherapy and autologous stem cell transplantation (SCT) in newly
      diagnosed chronic myelogenous leukemia patients aged below 56 years, not eligible
      for allogeneic SCT. Patients who had an HLA-identical sibling donor and no
      contraindication went for an allogeneic SCT (related donor, RD). After diagnosis,
      patients not allotransplanted received HU and IFN to keep WBC and platelet counts
      low. After 6 months patients with Ph-positive cells still present in the bone
      marrow received 1-3 courses of intensive chemotherapy. Those who became Ph
      negative after IFN + HU or after 1-3 chemotherapy courses underwent autologous
      SCT. Some patients with poor cytogenetic response were allotransplanted with an
      unrelated donor (URD). IFN + HU reduced the percentage of Ph-positive metaphases
      in 56% of patients, and 1 patient became Ph-negative. After one or two intensive
      cytotherapies 86 and 88% had a Ph reduction, and 34 and 40% became Ph-negative,
      respectively. In patients receiving a third intensive chemotherapy 92% achieved a
      Ph reduction and 8% became Ph-negative. The median survival after auto-SCT (n =
      46) was 7.5 years. The chance of remaining Ph-negative for up to 10 years after
      autologous SCT was around 20%. The overall survival for allo-SCT RD (n = 91) and
      URD (n = 28) was almost the same, i.e. approximately 60% at 10 years. The median
      survival for all 251 patients registered was 8 years (historical controls 3.5
      years). The role of the treatment schedule presented in the imatinib era is
      discussed.

PMID- 15870486
TI  - Comparison of epoetin alfa and darbepoetin alfa biological activity under
      different administration schedules in normal mice.
AB  - The unit of erythropoietic activity has long been the standard by which
      erythropoietic agents are judged, but the development of long-acting agents such
      as darbepoetin alfa has highlighted the shortcomings of this approach. To this
      point, we compared the in vivo activity of Epoetin alfa and darbepoetin alfa per
      microgram of protein core. Using the established mass-to-unit conversion for
      Epoetin alfa (1 microg congruent with 200 U), we then calculated darbepoetin alfa
      activity in units. Activity varied with treatment regimen (1 microg darbepoetin
      alfa congruent with 800 U for 3 times weekly dosing to 8,000 U for a single
      injection). This analysis reveals the inadequacy of evaluating darbepoetin alfa
      activity in terms of standard erythropoietic units. We therefore propose that for
      molecules with heightened biological activity, a more legitimate basis for
      comparison is the protein mass.

PMID- 15870487
TI  - Molecular basis of thalassemia syndromes in Serbia and Montenegro.
AB  - This study reports the molecular characterization of thalassemia syndromes in
      Serbian and Montenegrin populations. We identified eight beta-thalassemia
      mutations [codon 39 (C-->T), IVS-I-110 (G-->A), IVS-II-745 (C-->G), codon 44 (
      C), -87 (C-->G), IVS-II-1 (G-->A), IVS-I-6 (T-->C), IVS I-1 (G-->A)] in 70
      members of 29 families using polymerase chain reaction, reverse dot blot,
      amplification refractory mutation system and direct sequencing analysis.
      Hemoglobin (Hb) Lepore was found to be the most common cause of the thalassemia
      phenotype. Hb Sabine and alpha-thalassemia were detected as well. We also studied
      beta-globin gene cluster haplotypes and their association with the most common
      mutations. A novel haplotype associated with the Hb Lepore gene was identified.
      The results presented herein allowed the implementation of a prenatal diagnosis
      program in Serbia and Montenegro.

PMID- 15870488
TI  - Philadelphia-chromosome-positive T-lymphoblastic leukemia: acute leukemia or
      chronic myelogenous leukemia blastic crisis.
AB  - The Ph1 chromosome has rarely been reported in T-lineage acute lymphoblastic
      leukemia (T-ALL), and the clinical relevance of this translocation in T-ALL is
      currently unknown. In chronic myelogenous leukemia (CML) some data indicate
      derivation of T-cells from the leukemic clone and only a few cases of T-derived
      blastic crisis have been reported and quite often disputed. Particularly in cases
      identified initially in blastic crisis it may be difficult to distinguish those
      from Ph1-positive T-ALL. We herein report 2 patients who presented with a
      clinical picture of Ph1-positive T-ALL and who raised a differential diagnosis
      from T-cell blastic crisis of CML. We review the literature and suggest clinical
      and laboratory features that can help in the diagnosis. According to our
      literature review, 23 cases of Ph1-positive T-ALL and 44 cases of T-cell blastic
      crisis of CML, including ours, were reported. Some major differences between the
      two entities could help in establishing a diagnosis of Ph1-positive T-cell
      blastic crisis of CML vs. Ph1-positive T-ALL: Male sex and younger age was more
      predominant in T-ALL. While in most cases of CML blastic crisis there was a
      history of CML there was no such history in the T-ALL cases. Medullary
      involvement with lymphoblastic leukemia was present in all cases of T-ALL but
      only in about half of the cases of CML blastic crisis. None of the CML-blastic
      crisis cases tested by RT-PCR showed the minor breakpoint transcript, while 2
      cases with T-ALL had the minor breakpoint transcript and 1 had both transcripts.
      Combined morphologic and FISH analysis can help to distinguish between the two
      entities and was applied in one of our cases. Although both entities carry a
      severe prognosis, differentiating between them might have clinical relevance,
      especially in the imatinib era.

PMID- 15870489
TI  - Hand hygiene compliance in a hematology unit.
AB  - Transmission of pathogens from the hands of health care workers (HCWs) is the
      main cause of nosocomial infections, and hand hygiene is the single most
      important procedure to prevent it. At present, little is known about the
      adherence of HCWs to hand hygiene procedures in hematology units, where the
      patients are at high risk for acquiring hospital infections. In a prospective
      observational study, two observers monitored the hand hygiene compliance of HCWs
      in a hematology unit during 30-min observation periods distributed randomly
      during the daytime over 2 months. The prevalence of compliance with hand hygiene
      was 26% on 638 observed occasions. The noncompliance was higher among nurses
      [odds ratio (OR) 3.52, 95% confidence interval (CI) 1.85-6.70] and other HCWs (OR
      1.72, 95% CI 0.98-3.02) compared to physicians. The compliance rate differed from
      4 to 60% depending on the activity. The lowest compliance rate (4%) was observed
      before patient care and the highest (60%) was after insertion of invasive
      devices. When we classified the occasions for hand hygiene into 'before' and
      'after' activities, the compliance rates were 9 and 36%, respectively (OR 5.6,
      95% CI 3.4-9.0). In conclusion, noncompliance with hand hygiene was high in this
      hematology unit, especially among nurses and before activities. Variations with
      the type of HCW and activity suggest that targeted educational programs and
      feedback control may be useful.

PMID- 15870490
TI  - A case of pure red cell aplasia complicated with diffuse large B cell lymphoma, T
      cell-rich/histiocyte-rich variant: effectiveness of rituximab and implications
      for a common immunopathogenic role of B lymphocytes.
AB  - Diffuse large B cell lymphoma, T-cell-rich/histiocyte-rich variant (DLBL-TH), is
      characterized by the presence of neoplastic B cells set in a background
      containing numerous non-neoplastic T lymphocytes and histiocytes. We report here
      the case of a patient with DLBL-TH who developed overt pure red cell aplasia
      (PRCA) following chemotherapy and autologous peripheral blood stem cell
      transplantation. Posttransplantation bone marrow biopsies revealed the absence of
      erythroid precursors associated with lymphoid aggregates composed of B cells
      mixed with numerous T cells and histiocytes. Administration of rituximab has led
      to complete recovery of erythropoiesis, which was associated not only with B cell
      depletion but also with a marked reduction in bone marrow T cells and
      histiocytes. These observations strongly suggest the particular pathogenetic role
      of the patient's B cells in inducing PRCA and recruiting T cells and histiocytes
      in situ.

PMID- 15870491
TI  - Von Willebrand factor-cleaving protease activity remains at the intermediate
      level in thrombotic thrombocytopenic purpura.
AB  - A 59-year-old woman, diagnosed with chronic myelogenous leukemia (chronic phase)
      and treated with interferon-alpha for 13 years, developed renal failure. Renal
      biopsy showed thrombotic thrombocytopenic purpura, but intensive therapy
      including plasma exchange and steroid administration was not effective. The
      activity of von Willebrand factor-cleaving protease was detectable at the
      intermediate level (15-46%) during the clinical course, suggesting that this case
      was not compatible with the previously reported pattern of idiopathic or drug
      induced thrombotic thrombocytopenic purpura, but with the pattern associated with
      malignant disease or immunological disorders. Further studies to determine the
      effects of interferon-alpha on endothelial cells in chronic myelogenous leukemia
      patients are needed.

PMID- 15870492
TI  - Enhanced nitric oxide production is closely associated with erythropoietic
      activities in healthy adolescents.

PMID- 15870493
TI  - A novel homozygous mutation of PKLR gene in a pyruvate-kinase-deficient Korean
      family.

PMID- 15870494
TI  - Thrombocytosis in childhood.

PMID- 15870495
TI  - Calcaneal osteopenia is a new marker for arterial stiffness in chronic
      hemodialysis patients.
AB  - BACKGROUND: A high frequency of simultaneous low estimated bone mineral density
      (BMD) and atherosclerotic vascular disease is found in chronic dialysis patients.
      The degree of BMD may be closely related to the severity of atherosclerosis in
      dialysis patients. The purpose of this study was to determine the association of
      estimated BMD with severity of atherosclerosis using popular economical non
      invasive strategies in chronic dialysis patients. METHODS: This cross-sectional
      design study included 58 subjects receiving maintenance hemodialysis (HD)
      therapy. The mean age was 68 +/- 12 years (range 39-93), 22 subjects were female,
      and 26 subjects (45%) had diabetic nephropathy. The brachial-ankle pulse wave
      velocity (baPWV) and estimated BMD, using calcaneal quantitative ultrasound
      measurements of the osteo-sono index (OSI) were measured in all of the subjects.
      RESULTS: The mean levels of OSI and baPWV were 2.3 +/- 0.3 and 21 +/- 5 m/s,
      respectively. Based on single variable regression analysis, the C-reactive
      protein concentration correlated with baPWV (r = 0.272, p = 0.039), and the serum
      albumin concentration was inversely correlated with baPWV (r = -0.318, p =
      0.015). In addition, OSI had a strong negative correlation with baPWV (r = 
      0.470, p = 0.0002). To identify the independent factors correlating with baPWV,
      multivariate regression analysis was performed using confounding variables which
      had significant association in univariate analysis. OSI and diabetic nephropathy
      were found to be significant independent parameters. CONCLUSION: Calcaneal OSI, a
      surrogate marker for estimated BMD, has a strong ability to predict the severity
      of arterial stiffness independent of classical risk factors and markers of
      inflammation and malnutrition.

PMID- 15870496
TI  - Oral sildenafil for treatment of severe pulmonary hypertension in an infant.
AB  - We report the use of oral sildenafil in a 5-month-old preterm infant with severe
      bronchopulmonary dysplasia and pulmonary arterial hypertension refractory to
      inhaled nitric oxide treatment, maximal ventilatory support and conventional
      vasodilator therapy. Sildenafil was prepared as a liquid suspension by the method
      of trituration and administered via an orogastric tube to the patient. Forty
      eight hours after sildenafil treatment, echocardiography revealed that the
      tricuspid incompetence was substantially diminished and the contractility of both
      ventricles improved, indicating a marked reduction in pulmonary arterial
      pressure. Oral sildenafil treatment was continued for 6 months until complete
      resolution of pulmonary arterial hypertension, and oxygen supplement was weaned
      off. There was no adverse effect during the treatment period. Oral sildenafil may
      be useful in reducing pulmonary vascular resistance and can be considered for
      treatment of severe pulmonary arterial hypertension secondary to bronchopulmonary
      dysplasia.

PMID- 15870497
TI  - Intraoperative positive fluid balance improves tissue diffusion of ceftizoxime.
AB  - AIM OF STUDY: To demonstrate that administration of fluids and the consequent
      improvement of fluid balance during a surgical procedure can modify the tissue
      diffusion of ceftizoxime. METHODS: Twenty-eight patients (30-79 years) undergoing
      major abdominal surgery of the colon were administered ceftizoxime 30 mg/kg i.v.
      at induction of anesthesia. A sample of arterial blood was taken before
      administration of the drug (t0) and then again at the time of vascular occlusion
      of the colon segment to be removed (t1). A sample of the segment of removed colon
      was taken. The patients were divided into two groups on the basis of the fluid
      balance between t0 and t1: group A (n = 17) with a fluid balance <1,000 ml and
      group B (n = 11) with a fluid balance >1,000 ml. The parameters evaluated in each
      group were: weight, height and age of the patients, serum and tissue antibiotic
      concentration, percent ratio of serum and tissue concentration, time elapsed
      between t0 and t1, volume of administered fluids between t0 and t1, diuresis and
      hourly diuresis between t0 and t1 and body fluid distribution, obtained using a
      bioelectrical impedance analyzer. The mean results obtained in the two groups
      were then compared using Student's t test. RESULTS: The balance of fluids
      calculated up to t1 was 675 +/- 308 ml for group A and 1,411 +/- 405 ml for group
      B (p < 0.01). The means of the recorded values that showed statistically
      significant differences were: mean percent concentration ratio (43.6 +/- 8.4 vs.
      84 +/- 16%; p < 0.05), concentration in the colonic segment (16.3 +/- 7.9 vs.
      37.2 +/- 25.9 mg/ml; p < 0.05), urinary volume gathered up to t1 (538 +/- 557 vs.
      169 +/- 104 ml; p < 0.05), hourly urinary volume up to t1 (311.1 +/- 296 vs. 97.6
      +/- 77.9 ml/h; p < 0.05), percent variation of resistance (95.1 +/- 5.1 vs. 89.7
      +/- 8.6; p < 0.05). The other means did not show any significant statistical
      differences. CONCLUSIONS: A higher tissue water level seems to facilitate the
      penetration of the antibiotic into the tissue according to the pharmacokinetic
      characteristics of ceftizoxime: high amount of free drug (not bound to plasma
      proteins) and high hydrosolubility.

PMID- 15870498
TI  - In vitro activity of daptomycin versus linezolid and vancomycin against gram
      positive uropathogens and ampicillin against enterococci, causing complicated
      urinary tract infections.
AB  - OBJECTIVES: The existing therapeutic options for complicated urinary tract
      infections (UTI) caused by gram-positive uropathogens are not always optimal.
      Therefore, newer antimicrobials have to be assessed. METHODS: The antimicrobial
      activity of daptomycin was tested versus linezolid, vancomycin, and ampicillin
      (enterococci on ly), against pathogens from three different collections: (1)
      Uropathogens from hospitalized urological patients with complicated and/or
      hospital-acquired UTIs of the Urologic Clinic, Hospital St. Elisabeth, Straubing.
      (2) Uropathogens from a multicenter study comprising 37 urological centers
      throughout Germany. (3) Methicillin-resistant Staphylococcus aureus (MRSA)
      isolates of patients and staff within the Hospital St. Elisabeth, Straubing.
      Genotyping of the latter isolates was performed by pulsed-field gel
      electrophoresis. The minimal inhibitory concentrations (MIC) of daptomycin,
      linezolid, vancomycin, and ampicillin (only tested against enterococci) were
      determined by an agar dilution method using a multipointer with an inoculum of
      10(4) CFU per point. RESULTS: For all methicillin-susceptible Staphylococcus
      aureus (n = 25), MRSA (n = 49), methicillin-susceptible coagulase-negative
      staphylococci (n = 129), methicillin-resistant coagulase-negative staphylococci
      (n = 33), for Enterococcus faecalis (n = 289), and for Enterococcus faecium (n =
      4) the MICs ranged up to 2 mg/l (daptomycin, linezolid), up to 4 mg/l
      (vancomycin), and up to 8 mg/l (ampicillin, enterococci only) indicating that all
      strains were susceptible to the antibiotics tested. CONCLUSIONS: According to the
      in vitro activity daptomycin may be considered a promising antibacterial agent
      for the treatment of complicated UTI caused by gram-positive uropathogens. Thus,
      daptomycin should be evaluated in a clinical study.

PMID- 15870499
TI  - Characterization of fluoroquinolone and carbapenem susceptibilities in clinical
      isolates of levofloxacin-resistant Pseudomonas aeruginosa.
AB  - BACKGROUND: Pseudomonas aeruginosa can rapidly acquire resistance to antibiotics,
      including fluoroquinolones and carbapenems. METHODS: We characterized
      fluoroquinolone, carbapenem and other beta-lactam susceptibilities and analyzed
      fluoroquinolone and carbapenem resistance in 16 clinical isolates of levofloxacin
      resistant P. aeruginosa. RESULTS: All levofloxacin-resistant isolates showed high
      MICs (> or =32 microg/ml) for fluoroquinolones including norfloxacin,
      levofloxacin, sparfloxacin, gatifloxacin and pazufloxacin, whereas the MICs for
      sitafloxacin were between 2 and 16 microg/ml. These isolates had both a Thr83Ile
      mutation in GyrA and a Ser87Leu mutation in ParC. An additional mutation,
      Glu469Asp in GyrB, was detected in 3 isolates. Three of 16 isolates found during
      antibiotic therapy showed resistance to carbapenems (MIC, 16-32 microg/ml)
      because of a reduced production of OprD. Fluoroquinolones, beta-lactams and
      sulfamethoxazole-trimethoprim were used for 3 months before the isolation of
      levofloxacin-resistant P.aeruginosa. CONCLUSIONS: Emergence of resistant isolates
      to both fluoroquinolones and carbapenems during antibiotic therapy is a serious
      clinical problem. Our results suggest that susceptibilities to fluoroquinolones
      as well as carbapenems should be monitored during a prolonged course of
      antibiotic therapy against P. aeruginosa infection.

PMID- 15870500
TI  - Mutant prevention concentration of isoniazid, rifampicin and rifabutin against
      Mycobacterium tuberculosis.
AB  - BACKGROUND: Mutant prevention concentration (MPC) is a new parameter that may be
      of aid in determining the risk of resistant mutants being selected. METHODS: The
      MPCs of 224 Mycobacterium tuberculosis clinical isolates were estimated by
      plating more than 10(10) cells on drug-containing agar and determining the
      concentration that allowed no colony growth. Antibiotics used were isoniazid,
      rifampicin and rifabutin. RESULTS: The MPC90 of clinical isolates in our setting
      is 2.4, 2.2 and 0.4 mg/l for isoniazid, rifampicin and rifabutin, respectively.
      CONCLUSIONS: Isoniazid and rifampicin are two drugs that present a low risk of
      selection of resistant mutants when used in monotherapy. However, determination
      of the MPC of each strain can provide data to minimize this risk and thus enable
      treatment to be optimized.

PMID- 15870501
TI  - Fourth-generation cephalosporins: in vitro activity against nosocomial gram
      negative bacilli compared with beta-lactam antibiotics and ciprofloxacin.
AB  - The in vitro activity of two new expanded spectrum fourth-generation
      cephalosporins, cefepime and cefpirome, was compared with that of five
      antibacterial agents, ceftazidime, cefoperazone, cefotaxime, imipenem, and
      ciprofloxacin, that are commonly used in the treatment of serious infections
      caused by aerobic gram-negative bacteria. The agar dilution method described by
      the US National Committee for Clinical Laboratory Standards was used to determine
      the minimum inhibitory concentrations of antibiotics tested. Three hundred and
      two clinical isolates, representing a cross-section of Klebsiella and
      Enterobacter species and Pseudomonas aeruginosa were tested. The most potent beta
      lactams were imipenem, cefepime, and cefpirome, which demonstrated significant
      activity against the majority of strains in all three genera of bacteria, as did
      ciprofloxacin. Ceftazidime was active against P. aeruginosa, but was less potent
      against Klebsiella and Enterobacter species. Cefoperazone and cefotaxime were
      less active than ceftazidime against P. aeruginosa. Cefepime had slightly greater
      activity than cefpirome against the gram-negative bacteria tested. These data
      indicate that cefepime and cefpirome are highly active against many frequently
      resistant nosocomial bacterial strains that are traditionally responsible for
      difficult-to-treat infections.

PMID- 15870502
TI  - Determination of ReQuest-based symptom thresholds to define symptom relief in
      GERD clinical studies.
AB  - BACKGROUND/AIMS: The growing importance of symptom assessment is evident from the
      numerous clinical studies on gastroesophageal reflux disease (GERD) assessing
      treatment-induced symptom relief. However, to date, the a priori selection of
      criteria defining symptom relief has been arbitrary. The present study was
      designed to prospectively identify GERD symptom thresholds for the broad spectrum
      of GERD-related symptoms assessed by the validated reflux questionnaire (ReQuest)
      and its subscales, ReQuest-GI (gastrointestinal symptoms) and ReQuest-WSO
      (general well-being, sleep disturbances, other complaints), in individuals
      without evidence of GERD. METHODS: In this 4-day evaluation in Germany, 385
      individuals without evidence of GERD were included. On the first day,
      participants completed the ReQuest, the Gastrointestinal Symptom Rating Scale,
      and the Psychological General Well-Being scale. On the other days, participants
      filled in the ReQuest only. GERD symptom thresholds were calculated for ReQuest
      and its subscales, based on the respective 90th percentiles. RESULTS: GERD
      symptom thresholds were 3.37 for ReQuest, 0.95 for ReQuest-GI, and 2.46 for
      ReQuest-WSO. CONCLUSION: Even individuals without evidence of GERD may experience
      some mild symptoms that are commonly ascribed to GERD. GERD symptom thresholds
      derived in this study can be used to define the global symptom relief in patients
      with GERD.

PMID- 15870503
TI  - Novel measurement of rapid treatment success with ReQuest: first and sustained
      symptom relief as outcome parameters in patients with endoscopy-negative GERD
      receiving 20 mg pantoprazole or 20 mg esomeprazole.
AB  - BACKGROUND/AIMS: A prime concern for gastroesophageal reflux disease (GERD)
      patients is fast symptom control. Sparse valid information is available on the
      rapidity of the effect of proton pump inhibitors in provid ing symptom relief.
      The new reflux questionnaire ReQuest is validated for daily assessment of changes
      in GERD symptoms. Therefore, this study investigated the efficacy of 20 mg
      pantoprazole and 20 mg esomeprazole with regard to the time to symptom relief in
      patients with endoscopy-negative GERD (enGERD) using ReQuest. METHODS: 529
      patients were treated with pantoprazole or esomeprazole over 4 weeks. ReQuest
      symptom scores were assessed daily. The mean and median times to first and
      sustained symptom relief were determined. RESULTS: Median time to first symptom
      relief was 2 days for both drugs (intention-to-treat population). The median time
      to sustained symptom relief was 3 days shorter with pantoprazole (10.0 vs. 13.0
      days). The Hodges-Lehmann estimator for the difference in time to reach first and
      sustained symptom relief between both groups was 0.00 days. For both variables
      the one-sided 95% CI (Moses) was [0.00; infinity] documenting no significant
      differences between the treatment groups. CONCLUSIONS: The rapidity of symptom
      control can be evaluated by clinically significant parameters using ReQuest.
      Pantoprazole and esomeprazole are equally effective in the time to first and
      sustained symptom relief.

PMID- 15870505
TI  - Adenovirus-mediated gene transfer of superoxide dismutase and catalase decreases
      restenosis after balloon angioplasty.
AB  - BACKGROUND: Reactive oxygen species (ROS) production increases after injury and
      potentially contributes to restenosis after angioplasty. We therefore evaluated
      the effect of adenovirus-mediated gene transfer (Ad) of superoxide dismutase
      (SOD) and catalase (CAT) on ROS production and restenosis after balloon
      angioplasty. METHODS: O(2)(-) and H(2)O(2 )production was quantified in cultured
      cells after incubation with either LPS or CuSO(4). Angioplasty and gene transfer
      were performed in rabbit atherosclerotic iliac arteries. One artery was injected
      with AdSOD and AdCAT, while the contralateral artery was injected with an
      adenovirus carrying no transgene, and served as control. RESULTS: ROS production
      was significantly decreased after adenovirus-mediated gene transfer of SOD and
      CAT as compared with control. Treated arteries showed less restenosis (32 +/- 27
      vs. 63 +/- 19%, p = 0.003) and less constrictive remodeling (1.2 +/- 0.3 vs. 0.9
      +/- 0.2, p = 0.02) than control arteries. Arteries injected with AdSOD and AdCAT
      showed better vasoreactivity to acetylcholine (11 +/- 4 vs. -1 +/- 6%, p < 0.05),
      lower collagen density (43 +/- 16 vs. 53 +/- 23%, p = 0.03), and lower
      inflammatory cell infiltration (22 +/- 6 vs. 36 +/- 11%, p = 0.04) than control
      arteries. CONCLUSIONS: Our data suggest that adenovirus-mediated gene transfer of
      SOD and CAT reduced oxidative stress, restenosis, collagen accumulation, and
      inflammation and improved endothelial function after angioplasty.

PMID- 15870504
TI  - Transforming growth factor-beta is activated by plasmin and inhibits smooth
      muscle cell death in human saphenous vein.
AB  - BACKGROUND: The effect of activation of endogenous transforming growth factor
      beta (TGF-beta) on smooth muscle cell apoptosis was assessed in human saphenous
      vein. METHODS: Segments of human saphenous vein, obtained at the time of bypass
      graft surgery, were cultured for 14 days. During this time, smooth muscle cells
      accumulated in the intima as a result of proliferation and migration, partly
      counterbalanced by apoptotic cell death. RESULTS: Addition of exogenous TGF
      beta(1) had no effect on smooth muscle cell proliferation or apoptosis. However,
      antibody neutralization of endogenous TGF-beta(1) caused significant increases in
      smooth muscle cell death in the media and intima without any change in
      proliferation. A plasmin inhibitor (alpha-N-acetyl-L-lysine methyl ester), a
      specific urokinase-type plasminogen activator (uPA) inhibitor (amiloride) and an
      anti-catalytic anti-uPA antibody all caused decreases in the tissue content of
      active TGF-beta and increases in smooth muscle cell death in the media and
      intima. CONCLUSIONS: These data suggest that the amount of TGF-beta in human
      saphenous vein is sufficient, when in the active form, to protect smooth muscle
      cells against apoptosis. Adding exogenous TGF-beta(1) has no beneficial effect,
      but decreasing the amount of active TGF-beta causes smooth muscle cells to
      undergo apoptosis. Plasmin, generated by uPA, appears to be an important
      activator of endogenous latent TGF-beta.

PMID- 15870506
TI  - Effects of venlafaxine treatment on clozapine plasma levels in schizophrenic
      patients.
AB  - Depressive symptoms are found at any stage of schizophrenia, and antidepressant
      medication may be beneficial. Selective serotonin reuptake inhibitor
      antidepressants have been considered safe in schizophrenia but in combination
      with clozapine, that is widely used in chronic treatment-resistant schizophrenia,
      remarkable pharmacokinetic interactions can occur causing an elevation in
      clozapine plasma levels. To investigate this further, the plasma levels of
      clozapine were measured in 11 schizophrenic male patients with depressive
      symptoms who were administered both clozapine and venlafaxine. Low to moderate
      doses of venlafaxine did not seem to have any significant effect on clozapine
      plasma levels.

PMID- 15870507
TI  - Neuropsychological correlates of an attention-related negative component elicited
      in an auditory oddball paradigm in schizophrenia.
AB  - An attention-related, negative component can be detected between the N100 peak
      and 200 ms after stimulus by subtracting event-related potentials (ERPs) elicited
      to background tones when subjects ignore tones, from ERPs elicited to background
      tones when subjects attend to tones to detect target tones in an oddball
      paradigm. To clarify the cognitive significance of this component in
      schizophrenia, we examined the correlations of 24 patients between the amplitude
      and latency of the negative component and results obtained using
      neuropsychological measurement methods, including the Wisconsin Card Sorting
      Test, the Trail Making Test, the Verbal Fluency Test and some subtests from the
      Wechsler Memory Scale. The latency prolongation of the negative component
      correlated positively with the difference in performance time between parts A and
      B of the Trail Making Test, which estimates set shift, a frontal-lobe executive
      function, but not with any other neuropsychological measurements, while the
      amplitude showed no such correlation. These results suggest that the latency
      prolongation of the attention-related, negative component induced in an auditory
      oddball paradigm may serve as an index for frontal dysfunction in schizophrenia.

PMID- 15870508
TI  - Individual analysis of EEG band power and clinical drug response in
      schizophrenia.
AB  - The main purpose of this study was to investigate the relationship between short
      term clinical outcome and changes in electroencephalogram (EEG) power after drug
      treatment in patients with schizophrenia, and also to compare two different
      methods for quantitative EEG analysis. EEG power analysis was performed by both
      conventional fixed frequency band and adjusted frequency band based on individual
      alpha frequency (IAF) in 16 drug-naive patients before and after drug
      administration. In the theta bands determined by both conventional fixed band and
      IAF methods, the EEG power after treatment was larger than that before treatment.
      In addition, there was a correlation between EEG power and clinical drug response
      evaluated by changes in BPRS score. With regard to this correlation, IAF methods
      showed no apparent advantage over methods using conventional fixed frequency
      bands. Conventional quantitative EEG analysis can still serve as a useful tool
      for the assessment of short-term outcome of drug treatment.

PMID- 15870509
TI  - Information processing flow and neural activations in the dorsolateral prefrontal
      cortex in the Stroop task in schizophrenic patients. A spatially filtered MEG
      analysis with high temporal and spatial resolution.
AB  - Using a spatially filtered magnetoencephalography analysis (synthetic aperture
      magnetometry), we estimated neural activations in the Stroop task in nearly real
      time for schizophrenic patients with/without auditory hallucinations and for
      normal control subjects. In addition, auditory hallucinations were examined
      through the information processing flow of the brain neural network, including
      the frontal regions. One hundred unaveraged magnetoencephalography signals during
      the incongruent stimulus responses were analyzed with a time window of 200 ms in
      steps of 50 ms. In the 25-60-Hz band, cortical regions that showed significant
      current source density changes were examined for each time window. The three
      groups showed significantly decreased current source density, corresponding to
      neural activation, with temporal overlap along the fundamental cognitive
      information processing flow: sensory input system, executive control system,
      motor output system. Transient neural activations in the dorsolateral prefrontal
      cortex were bilateral with left-side dominancy for normal controls, left
      lateralized for nonhallucinators and right-lateralized for hallucinators. Our
      results suggest that the dysfunction in the left dorsolateral prefrontal cortex
      was related to auditory hallucinations, while the information processing flow was
      unaffected in the schizophrenic subjects in the Stroop task.

PMID- 15870510
TI  - Relationship between class I and II HLA antigens in schizophrenia and eye
      movement disturbances: a preliminary study.
AB  - The region coding human leukocyte antigen (HLA) on chromosome 6q21 was shown to
      be associated with both the vulnerability to schizophrenia and presence of eye
      movement disturbances (EMD). The aim of this preliminary study was to investigate
      how individual class I and II HLA antigens in schizophrenic patients may be
      related to schizophrenia and to the intensity of two kinds of EMD: fixation and
      smooth pursuit. The incidence of HLA antigens was compared between 40
      schizophrenic patients (17 male, 23 female) and 198 healthy control subjects (112
      male, 86 female). In schizophrenic patients, the intensity of EMD assessed by
      infrared reflectometry and quantified on a scale from 0 to 3 was correlated with
      the incidence of HLA antigens. A number of differences regarding HLA antigens
      were found between schizophrenic patients and healthy subjects. Significant
      correlation was also obtained between some EMD and a number of HLA antigens.
      Antigens A24 and A28 were found to occur in different frequencies in
      schizophrenic patients and healthy control subjects. They also correlated with
      EMD on the fixation and smooth pursuit tests. The results obtained show an
      association between HLA antigens and EMD as an endophenotypic marker of
      schizophrenia, and may add to other findings on susceptibility loci for
      schizophrenia on chromosome 6p21. A limitation of this study is a small number of
      investigated patients with schizophrenia.

PMID- 15870511
TI  - Prognostic factors in papillary thyroid cancer: an evaluation of 601 consecutive
      patients.
AB  - BACKGROUND: Although papillary thyroid cancer (PTC) is among the most curable
      cancer types, it can be a distressing disease for those patients suffering from
      frequent recurrences or even distant metastases leading to death. Age over 45
      years is the most important indicator of poor prognosis. Our aim was to evaluate
      markers which might predict the outcome of an individual patient better than does
      TNM classification alone. MATERIALS AND METHODS: Of 601 consecutive patients who
      underwent surgery for PTC, retrospectively we selected 36 patient pairs in which
      one recovered completely after primary surgery, and the other suffered from
      aggressive disease. Formalin-fixed, paraffin-embedded tumor samples from these 72
      patients were analyzed by immunohistochemistry for COX-2, MMP-2, VEGF-C, Bcl-2,
      Ki-67, and p21 expression. RESULTS AND CONCLUSIONS: None of the markers we
      studied showed a superiority over TNM classification in selecting patients likely
      to progress to aggressive disease. However, the expression of COX-2 and VEGF-C
      seemed to be increased in patients over 45, which could explain the more
      aggressive behavior of these tumors. Moreover, we found that age over 45, tumor
      size over 4 cm, extrathyroidal extension of tumor, nodal metastases, distant
      metastases, and stage IV had an unfavorable effect on survival.

PMID- 15870512
TI  - Establishment and characterization of 7 new monoclonal antibodies to tissue
      inhibitor of metalloproteinases-1.
AB  - Tissue inhibitor of metalloproteinases-1 (TIMP-1) plays a pivotal role in tissue
      remodeling processes, such as inflammation, wound healing and cancer invasion.
      Experimental results have pointed to a role in angiogenesis, cell proliferation,
      apoptosis and in malignant transformation. In clinical investigations high tumor
      tissue or plasma levels of TIMP-1 have been shown to have a strong and
      independent association with shorter survival time for breast and colorectal
      cancer patients, respectively. The purpose of this study has been to develop and
      characterize new anti-TIMP-1 monoclonal antibodies that may be useful in future
      development of TIMP-1 immunoassays.Peptide-based epitope mapping reveals linear
      epitopes. Surface plasmon resonance was used to determine antibody affinity and
      ability of antibodies to sandwich with each other. Antigen recognition was tested
      using ELISA and a chemiluminescence microtiter immunoassay format. Three
      antibodies recognized linear peptides. Estimated antibody affinities for TIMP-1
      ranged from 6.6 x 10(8) to>10(10) 1/M. Antibodies demonstrated different
      abilities in 'capture' and 'detection' positions in the sandwich experiment. All
      antibody pairs bound TIMP-1:ProMMP-9 complexes. TIMP-1:MMP-9 complexes were
      marginally reactive with five antibody pairs. The results suggest that the
      antibodies are unique. They may be useful in designing assays that recognize
      various forms of TIMP-1. Future studies will clarify whether the use of different
      combinations of antibodies will increase the clinical value of TIMP-1
      measurements in the treatment of cancer patients.

PMID- 15870514
TI  - A prospective evaluation of "see and treat" in women with HSIL Pap smear results:
      is this an appropriate strategy?
AB  - OBJECTIVE: The evaluation of abnormal cervical cytologic results is time
      consuming and costly. Most patients with high-grade squamous intraepithelial
      lesion (HSIL)-cervical intraepithelial neoplasia 3 (CIN 3) Pap smear results
      require an excisional procedure for diagnostic or therapeutic reasons. "See and
      treat" is a surgical procedure that involves a loop electrosurgical excisional
      procedure (LEEP) simultaneously to diagnose and to treat premalignant cervical
      disease in one visit. This procedure eliminates a second visit that typically is
      required for treatment. Data is lacking on the incidence of CIN 2 and CIN 3 in
      patients with an HSIL (CIN 2) Pap smear result. The objective of this study was
      to determine the incidence of CIN 2 and CIN 3 in patients with an HSIL (CIN 2)
      Pap smear using a see-and-treat protocol. METHODS: Women referred from local
      health departments to our university-based colposcopy clinic for evaluation of an
      HSIL (CIN 2) Pap smear result were evaluated for inclusion in a see and treat
      protocol. All eligible patients underwent colposcopy to rule out an obvious
      cervical carcinoma followed by an immediate LEEP to remove the transformation
      zone. A colposcopic impression was made using the Reid colposcopic index.
      Pathologic specimens were analyzed for the presence of CIN and the incidence of
      CIN 2 and CIN 3 was determined. RESULTS: To date, 51 patients have been enrolled
      in the study. Exclusion criteria included age less than 19 years, pregnancy, or
      medical contraindications. The mean age of the patients was 26 years (range, 19
      45 years). Forty-seven percent were white, 47% were black, and 6% were Hispanic.
      Of the 51 patients who underwent LEEP, 43 of 51 (85%) had satisfactory colposcopy
      and no patient had a lesion suspicious for cervical carcinoma. The average Reid
      colposcopic index was 3.5. Of the 51 LEEP specimens, 4 of 51 had no evidence of
      CIN (8%), 4 of 51 (8%) had CIN 1, 18 of 51 (35%) had CIN 2, and 25 of 51 (49%)
      had CIN 3. Eighty-four percent of patients had either CIN 2 or CIN 3, resulting
      in an overtreatment rate (CIN 1 or less) of 16%. CONCLUSIONS: The use of a see
      and treat protocol for patients with HSIL (CIN 2) Pap smear results may be an
      acceptable treatment option because of a high incidence of CIN 2 and CIN 3.

PMID- 15870515
TI  - Vulvar cancer in human immunodeficiency virus-seropositive premenopausal women: a
      case series and review of the literature.
AB  - This review describes three cases of human immunodeficiency virus-infected women
      who were diagnosed with vulvar cancer before age 40 years. A retrospective chart
      review was performed for three patients who were younger than 40 years of age and
      who had histologically confirmed invasive squamous cell carcinoma of the vulva
      diagnosed between 1999 and 2002. Demographic, clinical, and laboratory data were
      recorded. Three human immunodeficiency virus-seropositive women were diagnosed
      with invasive squamous cell carcinoma of the vulva, stages IA, IB1, and III. All
      cases were characterized by extensive surrounding vulvar, vaginal, and cervical
      intraepithelial neoplasia. CD4 cell counts were 250, 330, and 900 cells/uL. Two
      patients experienced previous acquired immune deficiency syndrome-defining
      illnesses: toxoplasmosis and cervical cancer. Vulvar cancer in young human
      immunodeficiency virus-seropositive women may be associated with other human
      papillomavirus-related diseases and immunosuppression, as evidenced by low CD4
      counts and the presence of antecedent acquired immune deficiency syndrome
      defining illnesses.

PMID- 15870516
TI  - Six cases of women with diethylstilbestrol in utero demonstrating long-term
      manifestations and current evaluation guidelines.
AB  - Diethylstilbestrol (DES), a nonsteroidal estrogen, was widely used in the United
      States from 1940 through 1971 to prevent pregnancy loss. In the late 1960s, an
      association was made with an increased incidence of clear cell adenocarcinoma in
      young women exposed in utero to DES. Additional study of these women over the
      next 35 years has shown an increased risk of other health problems including
      intraepithelial neoplasia, ectopic pregnancy, first trimester spontaneous
      abortion and second trimester pregnancy loss. The National Institutes of Health
      continues to fund studies to follow cohorts of DES-exposed mothers, daughters,
      sons and third generation children. The Centers for Disease Control have
      conducted a large DES Education Project and have established guidelines for
      management. The following six cases studies illustrate common problems seen in
      DES exposed daughters and management of problems encountered.

PMID- 15870517
TI  - The role treatment for cervical intraepithelial neoplasia plays in the
      disappearance of human papilloma virus.
AB  - OBJECTIVE: To explore the role played by excision of the transformation zone in
      women diagnosed with cervical intraepithelial neoplasia (CIN) in the
      disappearance of human papillomavirus (HPV). MATERIAL AND METHODS: In a
      retrospective, cohort study, women with CIN who were treated by loop
      electrosurgical excision procedure of the transformation zone were compared with
      another group of women with CIN who were managed expectantly. The decision to
      treat or manage expectantly was made by one of the authors on clinical grounds.
      All patients were evaluated with cervical cytologic analysis, pathologic
      examination of excised tissue, and HPV DNA testing, which was considered positive
      when high-risk HPV types were detected. Among women treated with loop
      electrosurgical excision procedure, the median lag time was calculated from
      diagnosis of CIN to treatment. The median time for conversion from HPV-positive
      to HPV-negative status in both groups was compared, as well as the 1- and 2-year
      cure rates (defined as converting to HPV-negative status) in the treated and
      untreated groups. RESULTS: In the treated group, 12% had CIN 1, 83% had CIN 2,3,
      2% had cancer, and 3% had normal pathologic results. In the untreated group, 82%
      had CIN 1, 16% had CIN 2,3, and 2% had normal pathologic results (p < 0.0001).
      The lag time from the initial diagnosis of CIN to treatment was less than 1
      month. The median follow-up time was 7 months (range, 1-121 months) in the
      treated group and 13 months (range, 1-70 months) in the untreated group. The 1
      year rates of conversion to HPV-negative status, defined as the cure rates in the
      treated and untreated groups, were 65% (+/- 6%) and 23% (+/- 7%), respectively,
      and the 2-year cure rates in the treated and untreated groups were 90% (+/- 4%)
      and 56% (+/- 11%), respectively (p < 0.0001). Median time to conversion to a
      negative HPV status was 7.7 months for the treated patients compared with 19.4
      months in the untreated patients (p < 0.0001). CONCLUSIONS: Women treated by loop
      electrosurgical excision procedure are more likely convert to HPV-negative status
      at 1 and 2 years and do so significantly sooner than those managed expectantly.

PMID- 15870518
TI  - Quantifying the risk of cervical intraepithelial neoplasia in women with
      unsatisfactory colposcopy results.
AB  - OBJECTIVE: To define the risk of high-grade cervical intraepithelial neoplasia
      (CIN 2,3) among women with unsatisfactory colposcopy results who underwent a loop
      electrosurgical excision procedure. METHODS: Loop electrosurgical excision
      procedures were performed for clinical indications by residents supervised by
      attending obstetrician-gynecologists at an urban public hospital referral clinic.
      Specimens obtained between July 1, 1996, and April 30, 2002, were retrieved
      retrospectively after grading and recording in an institutional database. The
      endpoint of interest was high-grade cervical disease, a composite of CIN 2, CIN
      3, and cancer, in excision specimens. RESULTS: Of 169 evaluable patients, five
      (3%) had cancer. High-grade disease was found in 6 of 21 patients (29%) without a
      colposcopic lesion, in 13 of 33 patients (36%) with only koilocytosis on
      colposcopic biopsy, in 15 of 55 patients (27%) with CIN 1, in 13 of 25 patients
      (54%) with CIN 2, and in 26 of 35 patients (74%) with CIN 3 (p < 0.001). High
      grade disease was associated with the grade of referral cytologic results,
      cytologic analysis repeated at colposcopy, and colposcopic biopsy (p < 0.001 for
      all). Limiting excision to women with cytologic results at the time of colposcopy
      read as atypical squamous cells of undetermined significance or worse yielded a
      high-grade disease prevalence of 12%, with a sensitivity of 92%, specificity 46%,
      negative predictive value 88%, and positive predictive value 56%. Referral
      cytologic results, colposcopic biopsy, age, and endocervical curettage results
      did not seem to identify women at low risk for high-grade disease. CONCLUSIONS:
      Women with negative cytologic results at the time of colposcopy have a low risk
      for high-grade disease and may avoid a loop electrosurgical excision procedure
      despite unsatisfactory colposcopy.

PMID- 15870519
TI  - Interobserver agreement for colposcopy quality control using digitized
      colposcopic images during the ALTS trial.
AB  - OBJECTIVE: To estimate interobserver agreement among colposcopy quality control
      reviewers viewing digitized cervical images during the Atypical Squamous Cells of
      Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study
      (ALTS). MATERIALS AND METHODS: Three colposcopy quality control reviewers
      independently examined modem-transferred digitized colposcopic images from
      subjects examined at four clinical centers. Reviewers indicated colposcopic
      impression, Reid colposcopic index scores, lesion size, and the technical quality
      of the image. Rates of agreement were evaluated using the kappa statistic and
      McNemar and Bowker tests of symmetry. RESULTS: Regarding colposcopic impressions,
      the average weighted kappa for pairs of initial reviewers was 0.36 (95%
      confidence interval, 0.33-0.39). kappa scores with respect to Reid colposcopic
      index, cervical image quality, and lesion size ranged from 0.23 to 0.28, 0.18 to
      0.27, and 0.33 to 0.42, respectively. CONCLUSIONS: Fair rates of agreement and
      poor to fair kappa scores among ALTS colposcopy quality control reviewers were
      noted for colposcopic impression, Reid colposcopic index scores, image quality,
      and lesion size. Great latitude exists in the interpretation of digitized
      cervical images. Poor image quality partially may explain these suboptimal
      results.

PMID- 15870520
TI  - Biopsy site selection during colposcopy and distribution of cervical
      intraepithelial neoplasia.
AB  - OBJECTIVE: To determine if sites selected for colposcopic biopsy and
      histologically proven cervical intraepithelial neoplasia are distributed randomly
      across the cervix. MATERIALS AND METHODS: Data were evaluated from all patients
      who visited the Walter Reed Army Medical Center Colposcopy Clinic during a 20
      month period. chi analysis was performed to assess the randomness of distribution
      of biopsies and cervical intraepithelial neoplasia. RESULTS: In 303 patients, 479
      biopsies were performed. The 11-, 12-, and 1-o'clock positions were selected for
      190 of 479 (40%) of biopsies, whereas the 6- and 12-o'clock positions were chosen
      for 186 of 479 (39%) of biopsies (p < 0.0001). Of 479 specimens, 161 (34%) were
      diagnosed as low-grade and 57 (12%) were diagnosed as high-grade. The 6-, 11-,
      and 12-o'clock positions accounted for 32 of 57 (56%) high-grade biopsies (p <
      0.0001). The 6- and 12-o'clock positions accounted for 61 of 161 (38%) low-grade
      biopsies (p < 0.0001). CONCLUSIONS: Loci selected for biopsy and histologically
      confirmed cervical intraepithelial neoplasia are not randomly distributed across
      the cervix. There is a predilection for the locations anterior and posterior to
      the cervical os.

PMID- 15870522
TI  - Cervicitis decidualis: a rare cause of antepartum hemorrhage.
AB  - This report describes the case of a patient with clinically antepartum hemorrhage
      and a colposcopic lesion resembling invasive cervical cancer. A 28-year-old
      patient sought treatment at 28 weeks of pregnancy with significant antepartum
      hemorrhage, clinically thought to be a result of placenta previa or abruptio
      placenta. Colposcopy showed a lesion resembling an invasive cervical cancer for
      which a biopsy was taken. Abnormal placentation was ruled out by ultrasound
      examination of the uterus. Histologic analysis showed a cervical decidual
      reaction with focal surface ulceration accounting for the cervical growth and
      hemorrhage. We describe an unusual cause of significant intrapartum hemorrhage
      attributable to cervical decidual reaction, mimicking abnormal placentation
      clinically and invasive cervical cancer colposcopically.

PMID- 15870521
TI  - The vulvodynia guideline.
AB  - OBJECTIVE: To provide a review of the literature and make known expert opinion
      regarding the treatment of vulvodynia. MATERIALS AND METHODS: Experts reviewed
      the existing literature to provide new definitions for vulvar pain and to
      describe treatments for this condition. RESULTS: Vulvodynia has been redefined by
      the International Society for the Study of Vulvovaginal Disease as vulvar
      discomfort in the absence of gross anatomic or neurologic findings.
      Classification is based further on whether the pain is generalized or localized
      and whether it is provoked, unprovoked, or both. Treatments described include
      general vulvar care, topical medications, oral medications, injectables,
      biofeedback and physical therapy, dietary changes with supplementations,
      acupuncture, hypnotherapy, and surgery. No one treatment is clearly the best for
      an individual patient. CONCLUSIONS: Vulvodynia has many possible treatments, but
      very few controlled trials have been performed to verify efficacy of these
      treatments. Provided are guidelines based largely on expert opinion to assist the
      patient and practitioner in dealing with this condition.

PMID- 15870523
TI  - Clinical question: ask the experts. Recurring painful vulvar ulcers.

PMID- 15870524
TI  - Home study course: winter 2005.

PMID- 15870526
TI  - Follow-up of cytologic predictions of endocervical glandular abnormalities:
      histologic outcomes in 123 cases.
AB  - OBJECTIVES: To determine histologic positive predictive values (PPVs) for three
      categories of cytologic reports of endocervical glandular abnormalities.
      MATERIALS AND METHODS: We obtained histologic follow-up for 100% of 67 cytologic
      predictions of adenocarcinoma in situ (AIS) and 82% of 39 predictions of possible
      AIS (?AIS) made over a 4-year period (1999-2002) and for 25% of 105 atypical
      endocervical cells (AEC) predictions over a 12-month period (2000). For each
      category of cytologic report, we determined the histologic yields of high-grade
      lesions overall and of high-grade glandular lesions. RESULTS: PPVs for
      predictions of AIS and ?AIS for high-grade lesions overall were 91% and 75% (p =
      .032), respectively, and those for high-grade glandular lesions were 88% and 72%
      (p = .046), respectively. For a cytologic report of AEC, of those with histologic
      follow-up, 9% had a high-grade lesion and 7% had a high-grade glandular lesion.
      CONCLUSION: Cytology can accurately predict AIS.

PMID- 15870527
TI  - Default from colposcopy and loop excision electrocautery procedure appointments
      in a military clinic.
AB  - OBJECTIVE: To determine the extent of nonadherence and impediments to care in a
      military colposcopy and loop excision electrocautery procedure (LEEP) clinic.
      MATERIALS AND METHODS: The nonadherence rate for colposcopy and LEEP appointments
      was determined for a 6-month period at Walter Reed Army Medical Center.
      Nonadherence was defined as failure to keep an appointment or cancellation within
      24 hours of the scheduled time. A nurse coordinator telephoned all nonadherent
      women. Women who agreed to participate were administered a structured survey to
      elicit their reasons for default from their appointments. RESULT: Sixty-one (15%)
      of 405 women were nonadherent. Of the 61 nonadherent women, 55 (90%) agreed to
      participate, 4 (7%) were unable to be contacted, and 2 (3%) declined
      participation. The average age of participants was 30 years. Beneficiary status
      of the 55 women was as follows: dependent, 27 (49%); active duty, 25 (45%);
      retired, 2 (4%); and veteran, 1 (2%). The most common reasons for default overall
      for 55 women were onset of menses (15 [27%]), unplanned family or personal event
      (9 [16%]), forgetting (8 [15%]), and work conflict (7 [13%]). Leading reasons for
      25 active duty women included work conflict (7 [28%]) and menses (6 [24%]).
      Leading reasons for 27 dependent women included menses (9 [33%]), unplanned
      family or personal event (6 [22%]), and forgetting (5 [19%]). CONCLUSIONS:
      Despite unrestricted access to care in the military clinic, the default rate was
      similar to rates reported for civilian clinics. Previsit interventions likely to
      improve compliance include sending informational packets to patients, better
      attention to scheduling around the time of expected menses, and initiating an
      appointment reminder system. To decrease the high percentage of nonadherence
      attributable to work conflicts for active duty women, supervisors need to be
      better informed about both medical and deployment implications of an unevaluated
      abnormal Pap smear.

PMID- 15870528
TI  - Should liquid-based cytology be repeated at the time of colposcopy?
AB  - OBJECTIVE: To evaluate the usefulness of repeated liquid cytology at the time of
      colposcopy. MATERIALS AND METHODS: We screened 5,100 women with liquid-based
      cytology and human papillomavirus (HPV) DNA testing. Women with any abnormal
      cytology result including atypical squamous cells of undetermined significance
      (ASCUS) or a positive high-risk HPV DNA test result were referred for colposcopy.
      One thousand three hundred thirty-three women returned for colposcopy with
      repeated cytology and cervical biopsy. RESULTS: Twenty-one women had less than
      high-grade squamous intraepithelial lesion (HSIL) screening cytology and cervical
      biopsy results; however, their repeated cytology at the colposcopy visit revealed
      HSIL, and excisional treatment was recommended. Repeated cytology at colposcopy
      significantly changed the clinical management for 1.6% (21) of 1,333 women.
      CONCLUSIONS: As an adjunct test to colposcopy, liquid cytology was similar to
      conventional cytology. Given current practice patterns, repeated liquid cytology
      at the time of colposcopy is rarely clinically useful.

PMID- 15870529
TI  - Association between invasive squamous cell carcinoma of the vulva and ABO blood
      group.
AB  - OBJECTIVE: To determine whether the distribution of ABO blood group among women
      with invasive squamous cell carcinoma (SCC) of the vulva is different from that
      among a population of women treated for nonneoplastic gynecologic disease.
      METHODS: A retrospective analysis of pathology reports and blood bank records
      from January 1996 through September 2003 was performed. The distribution of ABO
      blood group for 33 women diagnosed with invasive SCC of the vulva was determined.
      ABO blood group was also recorded for 100 female patients (controls) who
      underwent a gynecologic procedure for a nonneoplastic process during the period
      January 2003 through November 2003. The blood group phenotype distribution for
      the study groups and the controls was compared by an incidence ratio. RESULTS:
      Statistical analysis gave an incidence ratio for blood group types A and O of
      1.55 (p < .20) when the patients with invasive SCC of the vulva were compared
      with the controls. The p value was not significant. Similarly, the incidence
      ratio for blood group types B and O equaled 0.386 (p = 1). Again the p value was
      not significant. In fact, none of the incidence ratios calculated were
      statistically significant. Although not statistically significant, the incidence
      ratio for the invasive vulvar SCC group was >1. This may indicate that there is a
      trend for women with invasive SCC of the vulva to have blood group type A.
      CONCLUSIONS: Results of this study do not suggest an association between blood
      group type A, or any other blood group, and vulvar SCC. This study was similar in
      patient size to another study (33 patients with vulvar SCC vs. 39 patients with
      vulvar SCC, respectively). The disparity of the results in determining the
      significance of blood group type A as an associated factor for vulvar SCC in this
      and the other study may be due to the limited size of the study populations.
      Additional investigation is needed to further evaluate this issue.

PMID- 15870530
TI  - Telomerase activity as a potential diagnostic marker for triage of abnormal Pap
      smears.
AB  - OBJECTIVES: To determine whether there is an association between high levels of
      telomerase and premalignant cervical disease and to provide a preliminary
      analysis of telomerase activity as a potential triage strategy. MATERIALS AND
      METHODS: Premenopausal women were invited to participate in the study during
      routine gynecologic visits as well as visits where colposcopy was performed.
      Samples were taken from the cervix using a broom device and placed in cold
      phosphate-buffered saline. A total of 92 samples were evaluated. Cells were
      counted and lysed, and a semiquantitative measure of telomerase activity was
      determined using a commercially available telomerase enzyme-linked immunosorbent
      assay kit. The presence of human papillomavirus (HPV) types 16 and 18 was
      assessed by polymerase chain reaction analysis. One-way analysis of variance was
      used to test for the association of telomerase activity with cytology, HPV type
      16 or 18 status, and colposcopy and/or biopsy findings. RESULTS: When telomerase
      levels were analyzed according to Pap smear results, there were no differences
      among four groups of cytology findings (normal, atypical squamous cells of
      undetermined significance, low-grade squamous intraepithelial lesion, and high
      grade squamous intraepithelial lesion). When colposcopy and/or biopsy results
      were considered, significantly higher levels of telomerase were detected in
      cervical intraepithelial neoplasia (CIN) 2,3 samples than in normal Pap smear
      samples and CIN 1 samples (p = .035). There was no significant difference in
      telomerase levels between samples that tested positive for HPV type 16 or 18 and
      those that did not (p = .111). CONCLUSIONS: Telomerase levels were significantly
      higher in cytologic samples from women with biopsy-proven CIN 2,3 than in samples
      from women with normal cytology results or CIN 1. These results warrant larger
      studies to determine whether telomerase activity may be a useful triage tool for
      abnormal cytologic findings.

PMID- 15870531
TI  - Differentiating high-grade cervical intraepithelial lesion from atrophy in
      postmenopausal women using Ki-67, cyclin E, and p16 immunohistochemical analysis.
AB  - OBJECTIVE: In postmenopausal women, differentiating high-grade cervical
      intraepithelial neoplasia (CIN 2,3) from atrophic uterine cervical squamous
      epithelium histologically may pose a diagnostic challenge. Recent studies have
      indicated the value of using a combination of Ki-67, cyclin E, and p16
      immunohistochemical analysis in recognizing CIN 2,3. In this study, we compared
      the staining features of Ki-67, cyclin E, and p16 in cervix specimens from
      postmenopausal women to distinguish CIN 2,3 from atrophy. METHODS: Twenty-six
      formalin-fixed paraffin-embedded archival cervical specimens (4 biopsy, 8 laser
      cone, and 14 total hysterectomy samples) were selected from 25 women 50 to 80
      years of age (mean = 64 years). Cases included CIN 2,3 (n = 10), atrophy (n = 9),
      and coexistent CIN 2,3 and atrophy (n = 6). Slides were stained with monoclonal
      antibodies to Ki-67, cyclin E, and p16 using the avidin-biotin-peroxidase method.
      Strength of staining was graded as 1+ to 3+. Pattern of staining was described as
      diffuse, patchy, or scattered. Ki-67 staining restricted to the basal/parabasal
      zone was scored as negative. RESULTS: All CIN 2,3 cases demonstrated variable
      positivity for Ki-67, cyclin E, and p16. Most CIN 2,3 cases showed strong p16
      (81.3%) and Ki-67 (75.0%) reactivity, while only 31.3% of them showed strong
      cyclin E activity. Some CIN 2,3 cases demonstrated strong p16 but weak Ki-61 and
      cyclin E reactivity. All atrophic epithelia were negative for p16, cyclin E, and
      Ki-67. In coexistent CIN 2,3 and atrophy cases, the three-antibody panel clearly
      demarcated the transition from benign to neoplastic epithelia. CONCLUSION: P16 is
      the most valuable marker followed by Ki-67 for differentiating CIN 2,3. While
      cyclin E appears to add limited value on these two markers. Therefore, although
      the three-antibody immunohistochemical panel (p16, Ki-67, and cyclin E) can be a
      valuable adjunct to routine hematoxylin-eosin staining, it is also possible to
      use the two-antibody panel (p16 and Ki-67) to effectively distinguish CIN 2,3
      from atrophy in postmenopausal women.

PMID- 15870533
TI  - Detection of cervical human papillomavirus infection by in situ hybridization in
      fetuses from women with squamous intraepithelial lesions.
AB  - OBJECTIVE: To evaluate for human papillomavirus (HPV) infection in the cervix of
      fetuses from mothers with documented squamous intraepithelial lesions. METHODS:
      Fetal cervical epithelium was obtained from the Human Fetal Tissue Repository as
      per Institutional Review Board protocol. Fetal cervical epithelium was dissected,
      fixed in formalin, and embedded in paraffin. Sections were tested by in situ
      hybridization using a wide-spectrum HPV DNA probe. Cases were specimens from
      mothers with low- and high-grade squamous intraepithelial lesions, and controls
      were specimens from women with no documented squamous intraepithelial lesions.
      RESULTS: A total of 14 controls and 10 cases were evaluated for HPV DNA. No
      reactivity was detected in the controls. Two cases showed focal intracellular
      reactivity with the HPV DNA probe. CONCLUSION: To our knowledge, this is the
      first study demonstrate fetal cervical HPV infection due to intrauterine
      exposure. These findings have important implications in understanding the
      pathogenesis of cervical neoplasia and its management.

PMID- 15870532
TI  - Human papillomavirus infection and p16(INK4a) protein expression in vulvar
      intraepithelial neoplasia and invasive squamous cell carcinoma.
AB  - OBJECTIVE: Vulvar intraepithelial neoplasia (VIN) is defined histopathologically
      by distinctive abnormalities of cellular maturation and differentiation. The
      purpose of this study was to investigate the functional properties of VIN related
      to expression of p16(INK4a) protein as well as to detection of human
      papillomavirus (HPV) type 16 by real-time polymerase chain reaction (RT-PCR)
      analysis. METHODS: A total of 49 vulvar biopsy samples were examined by
      hematoxylin-eosin staining from benign/reactive lesions, condyloma acuminatum,
      VIN, and invasive squamous cell carcinoma (SCC). JC8 mouse monoclonal antibodies
      were used that recognize p16(INK4a) epitope at a dilution of 1:25. The reaction
      pattern for p16(INK4a) was graded in each sample between 0 and 3+. RT-PCR
      analysis of formalin-fixed paraffin-embedded sections determined positivity for
      HPV type 16. RESULTS: p16(INK4a) immunoreactivity was different in VIN 1, VIN 2,
      VIN 3, and squamous cell carcinoma. Strong expression of p16(INK4a) protein was
      observed in 92% (22 of 24) of VIN 2 and VIN 3 lesions and 100% (4 of 4) of
      invasive SCCs. Two (67%) of 3 VIN 2 lesions, 17 (81%) of 21 VIN 3 lesions, and 4
      (100%) of 4 SCCs were positive for HPV type 16 by PCR analysis. Two (20%) of 10
      VIN 1 lesions were immunoreactive for p16(INK4a), with only 1 lesion positive for
      HPV type 16. No p16(INK4a) immunoreactivity was observed in any of the
      benign/reactive and condyloma acuminatum lesions. In addition, none of the
      benign/reactive or condyloma lesions were positive for HPV type 16 by RT-PCR
      analysis. CONCLUSIONS: Upregulation of INK4a gene occurs in vulvar
      carcinogenesis. p16(INK4a) is not a sensitive marker for differentiation of
      benign vulvar squamous epithelium from condyloma acuminatum or VIN 1 lesions
      because most VIN 1 lesions are p16(INK4a) negative. Expression of p16(INK4a) may
      aid in the diagnosis of HPV-related lesions and as such may be of value as a
      surrogate marker in the diagnosis of vulvar premalignant and malignant lesions.

PMID- 15870534
TI  - The English National Health Service Cervical Screening Programme--approach to new
      technologies and quality assurance.

PMID- 15870536
TI  - Home study course: spring 2005.

PMID- 15870535
TI  - Cytopathology update on atypical squamous cells.
AB  - The most common abnormality reported by cervical cytology (Pap tests) is atypical
      squamous cells (ASC). The two subcategories are ASC of undetermined significance
      (ASCUS) and ASC, cannot exclude high-grade squamous intraepithelial lesion (ASC
      H). ASCUS show morphology suspicious for a low-grade lesion, while ASC-H cells
      are suspicious for a high-grade process. ASCUS account for most ASC reports, and
      the 2002 median ASCUS reporting rates were 3.1% for conventional smears and 4.1%
      for liquid-based preparations. Reporting rates for squamous intraepithelial
      lesions and cancer (SIL+) were also higher for liquid-based preparations, and
      thus the median ASC/SIL+ ratio was lower for liquid-based preparations (1.27)
      than for conventional smears (1.44). Interobserver reproducibility for ASC is
      generally considered lower than for other squamous epithelial abnormalities.
      Women with ASCUS may be managed by human papillomavirus DNA testing, repeated
      cytology, or colposcopy, while women with ASC-H should generally proceed to
      colposcopy.

PMID- 15870541
TI  - Coagulation factor XI: a database of mutations and polymorphisms associated with
      factor XI deficiency.
AB  - Hereditary factor XI deficiency is a rare bleeding disorder that is found
      worldwide. Rapidly increasing numbers of mutations and polymorphisms in various
      populations have been reported. However, the number of identified mutations given
      in recent literature and available databases is named to be not more than 35. We
      assumed that this is clearly too low and that to date no comprehensive survey of
      mutations associated with factor XI deficiency is available. To provide a
      complete database of mutations and polymorphisms associated with factor XI
      deficiency we collected all available data on hereditary factor XI deficiency
      from main biological and medical databases [http://ncbi.nlm.nih.gov/pubmed and
      http://ncbi.nlm.nih.gov/omim (OMIM reference 264900) and the Human Gene Mutation
      Database for F11 mutations http://uwcmml1s.uwcm.ac.uk/uwcm/mg/search/119891.html]
      as well as from contributions to international congresses. As of 8 June 2004 the
      number of reported causative mutations is 81, of which 12 have been described in
      unrelated individuals by more than one study group. For three frequently observed
      mutations [type II and type III mutations (Gln116Stop and Phe283Leu) and
      Cys38Arg] common founders have been described. Furthermore, 20 polymorphisms have
      been described in association with factor XI deficiency, three of which have been
      reported by two independent study groups. For the majority, allele frequencies
      have been published for in the Caucasian and/or Black population.

PMID- 15870542
TI  - Successful reversal of anticoagulant effect of superwarfarin poisoning with
      recombinant activated factor VII.
AB  - The use of second-generation anticoagulants termed "superwarfarins" as
      rodenticides, although widespread, is poorly controlled. Products containing
      superwarfarin have been marketed in over-the-counter rodenticides and can be
      easily purchased. Poor control potentiates the risk of accidental or intentional
      poisoning, but clinicians may underestimate the incidence of superwarfarin
      toxicity. Therefore, when cases of unexplained acquired coagulopathy and
      selective deficiency of vitamin K-dependent clotting factors occur in patients in
      the absence of liver disease or inhibitors, physicians should consider the
      possibility of superwarfarin poisoning as a cause. According to our own
      experience, recombinant activated factor VII (NovoSeven; Novo Nordisk, Bagsvaerd,
      Denmark) appears to be a safe and effective therapy for acute bleeding caused by
      superwarfarin poisoning. Due to the extended half-life of the second-generation
      rodenticides, follow-up therapy with oral vitamin K1 should be of long-term
      duration.

PMID- 15870543
TI  - The effects of ximelagatran and warfarin on the prophylaxis of a caval vein
      thrombosis and bleeding in the anaesthetized rat.
AB  - The antithrombotic and bleeding properties of the oral direct thrombin inhibitor
      ximelagatran and of warfarin were investigated in an experimental venous
      thrombosis and bleeding model in anaesthetized rats. Rats were randomized to
      receive ximelagatran (1-20 micromol/kg), warfarin (0.20-0.82 micromol/kg), or
      vehicle (tap water) once daily orally for 4 days before surgery. Thrombosis was
      induced by partial stenosis and application of ferric chloride to the wall of the
      abdominal vena cava under anaesthesia. Sixty minutes after thrombus induction,
      rats were sacrificed, thrombi harvested, and their fresh weight determined.
      Bleeding was determined as haemoglobin in fluid collected from the abdominal
      cavity. Blood samples were taken before thrombus induction and sacrifice for
      determination of coagulation parameters and plasma concentrations of melagatran,
      the active form of ximelagatran. Ximelagatran and warfarin dose-dependently
      reduced thrombus formation. The highest doses of ximelagatran and warfarin almost
      completely prevented thrombus formation; however, the increase in bleeding
      (versus vehicle) was significantly lower with the highest dose of ximelagatran
      than with the highest dose of warfarin. The oral direct thrombin inhibitor
      ximelagatran is thus as at least as effective as warfarin in the prevention of
      thrombus formation in this animal model, but with a wider separation between
      antithrombotic effects and bleeding.

PMID- 15870544
TI  - Effect of argatroban on the activated partial thromboplastin time: a comparison
      of 21 commercial reagents.
AB  - Argatroban is a direct thrombin inhibitor used for the treatment of heparin
      induced thrombocytopenia. The drug is administered by continuous infusion, at a
      recommended initial dose of 2 microg/kg per min, to achieve activated partial
      thromboplastin times (aPTTs) 1.5-3.0 times baseline. We evaluated the effect of
      argatroban, at clinically relevant concentrations, on aPTTs using 21 commercially
      available reagents. The aPTTs of plasma containing argatroban at 0.125-8.0
      microg/ml (final concentration) were assessed using each reagent and an ACL 3000+
      coagulation analyzer. Argatroban increased aPTTs (and aPTT ratios relative to
      control) in a broadly comparable fashion among reagents. Concentration-aPTT ratio
      profiles linearized well using logarithmic-logarithmic transformation (r > 0.98),
      with the regression slope taken as the reagent's sensitivity to argatroban.
      Sensitivity ranged from 0.304 +/- 0.006 to 0.364 +/- 0.007. Only the least and
      two most sensitive reagents (all now unavailable in the United States) differed
      significantly in sensitivity from the other reagents (P < 0.05). aPTT ratios of
      2.25 occurred for all reagents at 0.41-0.92 mug/ml argatroban, and for 14 (67%)
      reagents at 0.53-0.67 microg/ml. This corresponds to a approximately 0.5
      microg/kg per min dose difference in healthy subjects. We conclude that most aPTT
      reagents are similarly sensitive to argatroban, and reagent choice is unlikely to
      significantly affect argatroban monitoring in patients with heparin-induced
      thrombocytopenia.

PMID- 15870545
TI  - A study of the pharmacokinetics and safety of recombinant activated factor VII in
      healthy Caucasian and Japanese subjects.
AB  - In this randomized, placebo-controlled, double-blind, single-centre, dose
      escalation study, we report the first evaluation of the pharmacokinetics and
      safety of recombinant activated factor VII (rFVIIa) in healthy Caucasian and
      Japanese subjects. Thirty-two healthy subjects were stratified according to sex
      and ethnic group to receive single bolus intravenous injections of three
      different doses of rFVIIa (40, 80, 160 microg/kg rFVIIa) or placebo, each
      separated by a 7-day wash-out period. Blood samples were taken up to 24 h after
      dosing. The factor VII clotting activity appeared to be dose dependent, but
      independent of sex and ethnic group. Statistical analyses demonstrated no
      significant effect of dose, sex or ethnicity on the dose-normalized mean area
      under the plasma concentration-time curve AUC0-t, indicating dose
      proportionality. No serious adverse events or thromboembolic events were
      reported. Analyses of coagulation parameters did not suggest induction of
      systemic coagulation when dosing rFVIIa up to 160 microg/kg. In conclusion, the
      pharmacokinetics of rFVIIa in Caucasian and Japanese subjects are similar, and no
      safety issues were identified.

PMID- 15870546
TI  - von Willebrand factor multimer composition is modified following oral methionine
      load in women with thrombosis, but not in healthy women.
AB  - Hyperhomocysteinemia is associated with an increased risk of venous and arterial
      thrombosis, probably by inducing endothelial damage. Von Willebrand factor (VWF)
      is an endothelial marker protein. It is a plasma multimeric molecule that plays a
      thrombophilic role. Our purpose was to investigate VWF changes in patients with
      thrombosis following oral methionine load. We evaluated homocysteine levels and
      VWF parameters (plasma levels, activity, proteolysis fragments, and multimer
      composition) before and after methionine load in 42 women with venous or arterial
      thrombosis and in 36 healthy women. Methionine load induced mild
      hyperhomocysteinemia in 10 patients and two controls. No changes in VWF levels
      and activity were observed, but an increased amount of VWF proteolysis fragments
      was found post-load in patients and controls. VWF multimer composition was
      unaffected in controls, while a decrease of the largest VWF multimers was found
      in women with thrombosis. Homocysteine levels inversely correlated with the
      amount of the largest multimers in hyperhomocysteinemic patients. Large VWF
      molecules were probably released from endothelial cells following load, and
      rapidly cleaved by the specific VWF-cleaving protease. VWF proteolysis was
      enhanced in mild hyperhomocysteinemic patients, thus leading to downregulation of
      VWF size to smaller multimers.

PMID- 15870547
TI  - Low normal level of protein C or of antithrombin increases risk for recurrent
      cardiovascular events.
AB  - The relationship between haemostatic factors and recurrent cardiovascular events
      was investigated in patients enrolled with acute coronary syndrome (acute non-Q
      myocardial infarction or unstable angina pectoris). One hundred and fifteen
      patients, aged 64 +/- 10 years, were included in the study. Haemostatic
      parameters [prothrombin time, activities of factor VII, factor VIII, factor X,
      antithrombin (AT) and protein C (PC), and concentrations of free protein S,
      fibrinogen, D-dimer, prothrombin fragment 1+2, and thrombin-antithrombin complex]
      were measured four times: within 48 h of hospitalization, at discharge (days 5
      8), at 3 months and after 1 year. Screening for factor V Leiden mutation was also
      performed. Patients were followed for cardiovascular endpoints (new or refractory
      unstable angina pectoris, non-fatal myocardial infarction, stroke, or death) for
      an average of 555 days. Of all patients, 35 had an endpoint during the follow-up
      ("endpoint" group) and 80 patients did not ("no endpoint" group). Analysing the
      whole follow-up period, PC (P < 0.01) and AT (P < 0.01) were lower in the
      "endpoint" than in the "no endpoint" group. With 50% percentiles at enrollment,
      the odds ratio for getting an endpoint in the low (cut-off value < 100%) versus
      high PC group was 2.72 (95% confidence interval, 1.18-6.29; P < 0.05). Lower
      levels of AT (P < 0.05) and PC (P < 0.05) during the whole follow-up were
      associated with a shorter event-free time. In conclusion, lower PC and AT values,
      even within the normal range, seem to be associated with elevated risk for
      recurrent cardiovascular events and shorter event-free time in acute coronary
      syndrome patients.

PMID- 15870548
TI  - Homozygous factor V Leiden mutation in two siblings presenting with acute
      myocardial infarction: a rare cause of myocardial infarction in the young.
AB  - Although factor V Leiden mutation, is the most common established genetic risk
      factor for venous thrombosis, its effect on the development of myocardial
      infarction remains unclear. We describe a family case of homozygous factor V
      Leiden mutation in two siblings presenting with acute myocardial infarction as a
      rare cause of myocardial infarction in the young.

PMID- 15870549
TI  - Management of bleeding in a multi-transfused patient with positive HLA class I
      alloantibodies and thrombocytopenia associated with platelet dysfunction
      refractory to transfusion of cross-matched platelets.
AB  - Thrombocytopenia is a common condition in the critical care setting. Repetitive
      platelet transfusion might lead to formation of alloantibodies. HLA class I and
      human platelet antigen antibodies can lead to transfusion-refractory
      thrombocytopenia. Transfusion of cross-matched platelets often is effective in
      these patients. We report on the successful use of recombinant activated factor
      VII in an acute bleeding situation in a multi-transfused patient presenting with
      positive HLA class I alloantibody status and thrombocytopenia associated with
      platelet dysfunction refractory to even transfusion of cross-matched platelets.
      The 41-year-old female patient developed HLA class I antibodies during former
      episodes of massive transfusion. Her former medical history was empty concerning
      hemorrhagic events. During this specific bleeding episode the patient suffered
      from intractable profuse bleeding from the nasopharynx and oral cavity. Global
      coagulation tests were within the normal range. Platelet dysfunction was
      confirmed by PFA100. Initially the patient responded well to Desmopressin
      infusion, but after 36 h she became thrombocytopenic and refractory to even
      transfusion of cross-matched platelets. Recombinant activated factor VII was
      chosen as the last resort. Two identical boli of 160 microg/kg NovoSeven each
      were injected via a central line within an interval of 3 h. After the first
      injection bleeding was significantly reduced and vasopressor support
      discontinued. After the second bolus bleeding completely ceased and did not
      reoccur. We did not observe any side effects. The pluripotent hemostatic agent
      recombinant activated factor VII might be a new option in the treatment of
      hemorrhagic episodes in patients presenting with this rare disorder, especially
      when the patient is refractory to cross-matched platelets or matched platelets
      are not available.

PMID- 15870550
TI  - Multiple cycles of recombinant human thrombopoietin therapy in a patient with
      chronic refractory idiopathic thrombocytopenic purpura.
AB  - We describe a 41-year-old woman with chronic idiopathic thrombocytopenic purpura
      who received recombinant human thrombopoietin (rhTPO) therapy. rhTPO was
      administrated subcutaneously at a dosage of 1.0 mug/kg daily for a maximum of 14
      days until the platelet count was more than 50 x 10/l. The patient received three
      cycles (six, 13, and eight doses each) of rhTPO, each initiated when the platelet
      counts was less than 10 x 10/l. The platelet count increased to above 50 x 10/l
      on days 5, 11 and 8, and peaked at 456 x 10/l, 130 x 10/l and 82 x 10/l on days
      9, 15 and 13 in the three respective cycles, each followed by a gradual decline.
      The durations of platelet counts at more than 50 x 10/l in the three cycles were
      13, 7 and 10 days, respectively. rhTPO was well tolerated with no adverse event
      observed. Antibodies to rhTPO by enzyme-linked immunosorbent assay were not
      detected. Our observations suggested that rhTPO could transiently increase the
      peripheral platelet count in patients with chronic refractory idiopathic
      thrombocytopenic purpura. The reasons why the peak platelet counts decreased and
      the duration of response shortened after successive cycles of treatment were
      unclear.

PMID- 15870551
TI  - Treatment of intra-abdominal bleeding with recombinant activated factor VII in a
      patient with disseminated intravascular coagulation secondary to septic shock.
AB  - Although mainly indicated for treatment of bleeding in haemophilia patients with
      inhibitors, recombinant activated factor VII (rFVIIa) has also been successfully
      used in other situations. However, no data are available on its use in the
      treatment of disseminated intravascular coagulation (DIC) secondary to septic
      shock. We report a man with DIC and septic shock due to retrocaecal appendicitis
      and severe intra-abdominal bleeding after surgery. Despite conventional
      treatment, the bleeding persisted, and treatment with rFVIIa controlled the
      haemorrhage. No side-effects related to rFVIIa were noted. This case suggests a
      potential role of rFVIIa in the treatment of severe bleeding associated with DIC.

PMID- 15870552
TI  - Multi-centre investigation on reference ranges for ROTEM thromboelastometry.
AB  - Reagent-supported thromboelastometry (TEM) with the ROTEM Whole Blood Haemostasis
      Analyser is an enhancement of thromboelastography, a method that is increasingly
      used for the point of care monitoring of acute perioperative bleeding disorders.
      We investigated the reference ranges of two activated tests (INTEM and EXTEM) and
      a test analysing specifically the fibrin component of coagulation (FIBTEM) in a
      multi-centre approach. The reference ranges obtained for the clotting time (CT),
      clot formation time (CFT), alpha angle (ALP), maximum clot firmness (MCF) and
      clot lysis parameters were comparable from centre to centre. INTEM: CT equals;
      137-246 s, CFT equals; 40-100 s, MCF equals; 52-72 mm. EXTEM: CT equals; 42-74 s,
      CFT equals; 46-148 s, MCF equals; 49-71 mm. FIBTEM: MCF equals; 9-25 mm. ROTEM
      whole blood coagulation correlated weakly with a trend towards enhanced
      coagulation in females compared with males and in advanced age. The repeatability
      (within-run imprecision) of the results was dependent on the test with the
      following coefficients of variation: 1-5% (clot firmness, alpha angle), 3-12%
      (CT, CFT), 6-13% (FIBTEM clot firmness). Citrated blood samples were stable for
      ROTEM analysis stored within 6 h from drawing. In summary, the data showed that
      ROTEM thromboelastometry yields consistent values between centres and that
      providing general orientating reference ranges seems to be possible.

PMID- 15870554
TI  - Fibroids and in-vitro fertilization: which comes first?
AB  - PURPOSE OF REVIEW: There is no consensus about the impact of uterine fibroids on
      fertility. This review explores past and recent studies that investigated the
      effects of submucosal, intramural, and subserosal fibroids on in-vitro
      fertilization (IVF) outcomes. We discuss the importance of proper evaluation of
      the uterus and endometrial cavity, and current options for optimal fibroid
      management in patients desiring fertility. RECENT FINDINGS: Several studies have
      reviewed the data on fibroids and infertility, further exploring this potential
      relationship. Two recent studies investigated reproductive outcomes before and
      after myomectomy, and IVF outcomes based on fibroid size and location. Both
      studies concluded that fibroids can impair reproductive outcomes. Several papers
      thoroughly reviewed medical and surgical management options for patients with
      fibroids and desired fertility. Although several medical therapies may reduce
      fibroid volume or decrease menorrhagia, myomectomy remains the standard of care
      for future fertility. Recent data identified an increased rate of pregnancy
      complications after uterine artery embolization compared with laparoscopic
      myomectomy. A new procedure, magnetic resonance imaging-guided focused ultrasound
      ablation, shows promise for the management of symptomatic fibroids, and possibly
      for the management of fibroids prior to pregnancy. As with embolization, more
      data are needed to evaluate postprocedure fertility and pregnancy outcomes.
      SUMMARY: Fibroid location, followed by size, is the most important factor
      determining the impact of fibroids on IVF outcomes. Any distortion of the
      endometrial cavity seriously affects IVF outcomes, and myomectomy is indicated in
      this situation. Myomectomy should also be considered for patients with large
      fibroids, and for patients with unexplained unsuccessful IVF cycles.

PMID- 15870555
TI  - Effect of repeated assisted reproduction techniques on the ovarian response.
AB  - PURPOSE OF REVIEW: Despite the increasing success of assisted reproduction
      techniques, most couples need more than one cycle of controlled ovarian
      hyperstimulation to achieve a pregnancy. The effect of several cycles on the
      ovarian response in subsequent cycles is a concern for gynaecologists and
      patients. In addition, egg donors have the possible risk of an ovarian reserve
      decrease. In this review, we present published evidence on the effects of
      repeated assisted reproduction techniques on the ovarian response. RECENT
      FINDINGS: Recent available data indicate that ovarian response persists with
      subsequent cycles of controlled ovarian hyperstimulation in terms of oocytes
      being retrieved, although it is not clear whether an increased level of
      gonadotropins is required to achieve this response. There is a decrease in the
      number of oocytes retrieved in subsequent cycles due to increased female age as
      more cycles are needed. The oocytes retrieved in one cycle seem to come from the
      antral pool that otherwise would be atretic due to dominant follicle selection.
      SUMMARY: The mechanisms involved in the recruitment from atresia of more than one
      follicle are discussed and it is shown that repetitive ovarian stimulation does
      not appear to affect the ovarian reserve. Published evidence shows that
      gonadotropins alter the physiologic selection of one single dominant follicle but
      do not accelerate the recruitment of follicles from further cycles, confirming
      that there is no detrimental effect on ovarian function after repetitive
      controlled ovarian hyperstimulation.

PMID- 15870556
TI  - Natural killer cells and reproductive failure.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update of what is
      known about the role of natural killer cells in reproduction. RECENT FINDINGS: In
      humans, natural killer cells are present in abundance in the uterus and appear to
      play an important role in early pregnancy. Women with reproductive failure have
      been shown to have higher levels of natural killer cell numbers and activity in
      peripheral blood. The evidence relating to uterine natural killer cells, however,
      is contradictory. While earlier studies suggested an increase of uterine natural
      killer cells in women with recurrent pregnancy loss, more recent investigations
      have not confirmed this trend. Uterine natural killer cell number or activity
      appear to be higher in spontaneous abortions with normal chromosomes compared
      with chromosomally abnormal pregnancies. Furthermore, a rise of the cytotoxic
      CD56(dim)CD16+ natural killer cell subset is seen in the follicular fluid of
      patients with idiopathic infertility and it is postulated that this increase may
      decrease fertilization rates in this group. SUMMARY: Natural killer cell number
      and activity appear to be altered in women with reproductive failure although it
      is unclear if the difference is a cause or effect of reproductive failure.
      Whether natural killer cells are increased or decreased depends on whether
      peripheral blood, endometrium or first-trimester decidua is analyzed. Until more
      is known about the role of natural killer cells in normal pregnancy, there does
      not appear to be any benefit in offering natural killer cell testing to women
      with reproductive failure outside of research protocols.

PMID- 15870557
TI  - Is laparoscopy necessary before assisted reproductive technology?
AB  - PURPOSE OF REVIEW: Laparoscopy is widely used during infertility work-up,
      although it is sometimes unnecessary. This review highlights when laparoscopic
      intervention should be used in women undergoing assisted reproductive technology
      cycles. RECENT FINDINGS: There is no evidence for an increase in pregnancy rates
      in assisted reproductive technology cycles following surgical treatment of pelvic
      adhesions or endometriosis with laparoscopy. If the patient has bilateral visible
      hydrosalpinges, laparoscopy may be an option for evaluation of the tubes and
      treatment with salpingectomy in order to enhance the chance of pregnancy before
      commencing an assisted reproductive technology cycle. Laparoscopic ovarian
      drilling before assisted reproductive technology may be considered a therapeutic
      option in polycystic ovary disease patients who previously had severe ovarian
      hyperstimulation syndrome. Finally, laparoscopy may be useful in replacing the
      transposed ovaries to their original sites in the pelvic cavity in previously
      treated cancer patients so that monitoring of the controlled ovarian
      hyperstimulation and the oocyte aspiration would be much easier during the
      assisted reproductive technology cycles. SUMMARY: Laparoscopy should be
      considered before assisted reproductive technology cycles if the procedure
      diagnoses and treats a pelvic pathology at the same time and if laparoscopic
      intervention increases the chance of pregnancy following these cycles.

PMID- 15870558
TI  - Estrogen and folliculogenesis: is one necessary for the other?
AB  - PURPOSE OF REVIEW: During folliculogenesis the primordial follicle undergoes
      several steps of maturation in order to develop into a preovulatory follicle. The
      exact role of estrogen during this process has not yet been fully assessed.
      RECENT FINDINGS: Estrogen appears to regulate cyclic gonadotropin release via its
      action on estrogen receptor alpha in the hypothalamus/hypophysis axis and to
      enhance folliculogenesis through its actions via estrogen receptor beta in the
      ovary. In addition, a role of estrogen during the very early stages of
      folliculogenesis is possible. However, it is likely that oocyte quality and
      developmental potential are not estrogen dependent. This might explain the lack
      of association between estrogen and in-vitro fertilization outcome in humans.
      SUMMARY: The advent of knockout mice models has enhanced our understanding of the
      role of estrogen during folliculogenesis. Existing data suggest that estrogen
      might be involved in the very early steps of this process, but its role in
      sustaining ovulation is mainly central.

PMID- 15870559
TI  - The significance of sperm nuclear DNA strand breaks on reproductive outcome.
AB  - PURPOSE OF REVIEW: A growing body of evidence indicates that ejaculated
      spermatozoa from men being treated with intracytoplasmic sperm injection contain
      nuclear abnormalities. Many of these nuclear anomalies manifest themselves as
      breaks in the sperm nuclear DNA. This review examines the mechanisms involved in
      generating DNA strand breaks during spermatogenesis in the human, the main
      techniques used to assess the sperm nucleus and the evidence, in relation to
      assisted reproduction, showing that sperm nuclear DNA strand breaks may impact on
      reproductive outcome. RECENT FINDINGS: Techniques such as the TUNEL assay and the
      sperm chromatin structure assay both show increased levels of DNA abnormalities
      in spermatozoa from men who have poor semen parameters. The reproductive
      parameters affected by an increased presence of DNA abnormalities in ejaculated
      spermatozoa include fertilization, blastocyst development, and pregnancy rates.
      SUMMARY: There is accumulating evidence linking sperm nuclear DNA anomalies to
      poor reproductive outcome in relation to assisted reproduction technologies. The
      tests currently available only provide an inkling of the impact of sperm nuclear
      DNA abnormalities on reproductive outcomes. Although the impact an abnormal
      paternal genome may have on reproductive outcome is unquestionably less than that
      of its female counterpart, it cannot be ignored.

PMID- 15870560
TI  - Adenomyosis: what is the impact on fertility?
AB  - PURPOSE OF REVIEW: This review is timely and relevant for several reasons. The
      incidence of adenomyosis begins to rise from the mid-thirties. Moreover, more
      women are delaying their first pregnancy until later in their thirties or
      forties, and consequently adenomyosis is encountered more frequently in the
      fertility clinic during diagnostic work-up. Furthermore, it is difficult to
      diagnose adenomyosis before surgery, because there are no pathognomonic signs,
      symptoms or physical findings. Finally, reference data are very limited. RECENT
      FINDINGS: This review refers to adenomyosis of the uterus as a factor in female
      infertility. The clinical presentation of adenomyosis uteri is also reviewed, as
      well as animal and human studies concerning the effect of adenomyosis in female
      infertility. Different treatment options are discussed, especially those
      referring to patients who wish to maintain their fecundity. SUMMARY: Uterine
      adenomyosis remains a fairly frequent and debilitating disease that will be
      encountered with increasing incidence in the infertile female population. While
      spectacular advances have been made in recent years in the non-invasive diagnosis
      of the condition, non-surgical treatment options for infertile patients with
      adenomyosis arise but need to be confirmed in larger series.

PMID- 15870561
TI  - Uterine contractility and embryo implantation.
AB  - PURPOSE OF REVIEW: The aim of this article is to assess the importance of uterine
      contractility in the implantation of human embryos. RECENT FINDINGS: Recent
      findings show that the receptive phase of the endometrium seems to occur in close
      association with the appearance of pinopodes and endometrial integrins that may
      be activated by the IL-1 system. Throughout the menstrual cycle wavelike activity
      patterns of the uterus were identified with adequate wave patterns appearing to
      be related to successful reproduction in spontaneous cycles and in assisted
      reproduction. Such patterns are controlled by steroid hormones. Embryo attachment
      to the predecidualized endometrium and its invasion may be determined by the
      expression of proteolytic enzymes that require uterine quiescence for
      implantation. The uterine activity was detected both in vitro and in vivo by
      using invasive intrauterine pressure and noninvasive ultrasound approaches.
      Progesterone promotes local vasodilatation and uterine musculature quiescence by
      inducing nitric oxide synthesis in the decidua. At present, until new evidence
      emerges to demonstrate otherwise, the effects of progesterone are, directly or
      indirectly, the only determinant of endometrial preparation for embryo nidation,
      with the induction of uterine quiescence being one of these effects. SUMMARY:
      Adequate uterine contractility may provide for gamete/embryo transportation
      through the utero-tubal cavities and successful embryo implantation in
      spontaneous or assisted reproduction. Inadequate uterine contractility may lead
      to ectopic pregnancies, miscarriages, retrograde bleeding with dysmenorrhea and
      endometriosis.

PMID- 15870562
TI  - Luteal phase support in assisted reproductive technology.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss luteal support in
      assisted reproduction and to provide an evidence-based overview of the current
      options available. RECENT FINDINGS: The luteal phase has been found to be
      defective in virtually all of the stimulation protocols used for in-vitro
      fertilization. Common mechanisms such as supraphysiological levels of estradiol,
      decreased output of luteinizing hormone, inhibition of the corpus luteum and
      asynchronization of estradiol and progesterone may be involved in insufficient
      function of the corpus luteum in assisted reproductive technology. SUMMARY:
      Gonadotropin releasing hormone agonist undoubtedly provides benefits in
      stimulated cycles, however it also has adverse effects, inhibition of the corpus
      luteum together with supraphysiological hormonal profiles finally leading to
      luteal phase defects. Luteal phase support with human chorionic gonadotropin or
      progesterone after assisted reproduction results in increased pregnancy rates.
      The role of luteal phase support in these cycles has also been recently
      elucidated. Use of human chorionic gonadotropin for luteal phase support is
      associated with a marked increase in the risk of ovarian hyperstimulation
      syndrome, therefore progesterone is the preferred choice. Data on the benefits of
      estrogen supplementation are conflicting. Among the routes of progesterone
      administration, reductions in pregnancy rates are noted on oral administration.
      In spite of a lack of statistical significance, the intramuscular route seems to
      be more beneficial than the vaginal route when considering rates of ongoing
      pregnancy and live birth. Further clarification is needed on the ideal dose, the
      optimal route and the duration of progesterone administration in assisted
      reproduction.

PMID- 15870563
TI  - Noninvasive methods to assess embryo quality.
AB  - PURPOSE OF REVIEW: The present review examines recent publications concerned with
      the issue of the number of embryos to replace in an in-vitro fertilization cycle
      and in doing so concentrates on the proposed selection methods that may allow us
      to transfer one or two embryos. RECENT FINDINGS: A number of techniques that will
      allow us to ascertain the health and viability of the embryo are discussed. These
      range from methods to assess embryo morphology to those that require more complex
      forms of technology. Logically the use of the simple methodology is more
      abundant. However, there is accumulating evidence that some of the more complex
      assessment techniques may be ready for a more general use. SUMMARY: In performing
      embryo selection we need to develop processes that will be extremely critical,
      allowing us to limit the number of embryos replaced without detriment to
      pregnancy rates.

PMID- 15870564
TI  - Embryo transfer: factors involved in optimizing the success.
AB  - PURPOSE OF REVIEW: Embryo transfer is arguably the most critical step in assisted
      reproduction. The purpose of this article is to review the different aspects of
      the procedure in the light of recent evidence. RECENT FINDINGS: Randomized trials
      have shown that significantly higher pregnancy rates are obtained when embryo
      transfer is performed under ultrasound guidance, the embryos are deposited in the
      middle part of the uterine cavity, an atraumatic technique is used and when low
      dose aspirin is routinely administered following the procedure. Blood in the
      catheter and leaving the embryos inside it for more than 120 s diminish the
      pregnancy rate significantly. Air in the catheter, immediate removal of the
      catheter, performing two transfers in the same cycle, prolonged bed rest, sexual
      intercourse after embryo transfer or the use of sildenafil do not affect the
      results. Based on currently available evidence, Cochrane reviews have concluded
      that the live birth rate is not increased by delaying embryo transfer from day
      two to three or to the blastocyst stage, and that single embryo transfer leads to
      lower live birth rates than the transfer of two embryos. The value of a mock
      transfer a few days before the actual procedure has been challenged as the
      position of the uterus may change. The effect of holding the cervix with a
      volsellum, routinely administering antibiotics and the superiority of one
      catheter over the others is still to be determined. SUMMARY: Recent studies
      confirm the importance of the various aspects of embryo transfer. More randomized
      studies are needed to further evaluate them.

PMID- 15870565
TI  - Fertility preservation options for female patients with malignancies.
AB  - PURPOSE OF REVIEW: Preservation of fertility in female patients diagnosed with
      cancer has recently been an area of intensive investigation. This review
      summarizes available options and discusses recently published data concerning
      experimental methods. Specific strategies for fertility preservation in women
      with gynecologic malignancies are also presented. RECENT FINDINGS: Success with
      ovarian stimulation protocols using tamoxifen or aromatase inhibitors has
      recently been reported for women with breast cancer who attempt embryo
      cryopreservation prior to chemotherapy. The first embryo transfer using oocytes
      retrieved from cryopreserved ovarian tissue implanted at a heterotopic location,
      the first pregnancy following orthotopic transplantation of cryopreserved ovarian
      tissue, and increasing success with oocyte cryopreservation were also reported.
      SUMMARY: Fertility preservation in female patients with cancer has become an
      important health issue due to increasing survival rates and delayed childbearing
      especially in Western countries. Radical vaginal trachelectomy for cervical
      cancer, conservative surgery for ovarian tumors, and progestin treatment in
      endometrial cancers may be considered at early stages in order to preserve
      fertility. Embryo cryopreservation is an established technique that is available
      for fertility preservation, providing a delay in the initiation of chemotherapy
      or radiotherapy is acceptable, and a partner or donor sperm is available.
      Additional techniques that could be offered after counseling the patient about
      their experimental nature include oocyte cryopreservation, ovarian
      cryopreservation, and gonadotropin-releasing hormone agonist co-treatment with
      chemotherapy. Improvement of these techniques as well as better characterization
      of their success rates and risks await further investigation.

PMID- 15870566
TI  - Reproduction in same sex couples: quality of parenting and child development.
AB  - PURPOSE OF REVIEW: Same sex couples are steadily becoming more open about their
      relationships. One consequence of this growing openness is that more couples of
      the same sex are choosing to have children and infertility treatment centers are
      increasingly faced with requests for assistance in creating these families. The
      aim of this review is to address new trends in reproduction in same sex couples,
      to consider the quality of parenting in lesbian mother and gay father households,
      and to review the literature on the development of children raised by same sex
      couples. RECENT FINDINGS: The current literature on these families is limited by
      small sample sizes and a predominance of studies of lesbian mothers and their
      children, with few studies of gay fathers and their children. A recent study of
      adolescents living with same sex parents recruited from a large national sample
      supports the notion that adolescents raised by same sex couples are doing well
      psychologically and are not more likely to be homosexual. The authors concluded
      that it was the quality of parenting, not parental sexual orientation that
      accounted for developmental differences. SUMMARY: The literature supports the
      notion that children of lesbian mothers and gay fathers are not more likely to
      become homosexual and are not measurably different from children raised by
      heterosexual parents in terms of personality development, psychological
      development, and gender identity. Larger longitudinal studies of same sex
      parents, particularly gay men, are needed, including those who choose to become
      parents through the use of assisted reproduction.

PMID- 15870567
TI  - Bibliography. Current world literature. Fertility.

PMID- 15870569
TI  - Value-based medicine: the new paradigm.

PMID- 15870570
TI  - Review of optical coherence tomography for intraocular tumors.
AB  - PURPOSE OF REVIEW: Optical coherence tomography has assumed an important role in
      the management of numerous ocular conditions. With regard to ocular oncology,
      optical coherence tomography can illustrate retinal changes overlying choroidal
      tumors. Some of these features include photoreceptor loss, intraretinal edema,
      and retinal thinning overlying choroidal nevus; fresh subretinal fluid with
      preservation of photoreceptors overlying choroidal melanoma; and intraretinal
      edema, retinoschisis, and retinal thinning overlying irradiated choroidal
      melanoma. RECENT FINDINGS: The optical coherence tomography features of tumors of
      the retinal pigment epithelium include typical findings of peaked vitreoretinal
      traction and retinal disorganization with combined hamartoma of the retina and
      retinal pigment epithelium, full-thickness retinal shadowing with congenital
      simple hamartoma, and photoreceptor loss and retinal thinning overlying
      congenital hypertrophy of the retinal pigment epithelium. SUMMARY: Optical
      coherence tomography of retinal tumors, such as retinoblastoma and astrocytic
      hamartoma, reveals full-thickness replacement of the retinal anatomic layers with
      the tumor and shadowing corresponding to the intralesional calcification. For all
      intraocular tumors, optical coherence tomography provides valuable information
      regarding the status of the retina and the retinal pigment epithelium and can be
      useful in ascertaining reasons for visual loss.

PMID- 15870571
TI  - The impact of diabetic retinopathy on health-related quality of life.
AB  - PURPOSE OF REVIEW: To review recent evidence evaluating the effect of diabetic
      retinopathy and diabetic macular edema on health-related quality of life. RECENT
      FINDINGS: A search of PubMed was conducted according to a strategy that combined
      the text words 'diabetic retinopathy' and 'quality of life' (n = 91; November 11,
      2004) and 'diabetic macular edema' and 'quality of life' (n = 6; November 22,
      2004). The Methods sections of all abstracts were reviewed for valid generic or
      disease-specific instruments used to evaluate health-related quality of life. In
      addition, abstracts were reviewed to ensure that the study sample was made up
      predominantly of diabetic individuals. Recent data suggest that persons with
      diabetic retinopathy are willing to trade off significant time to eliminate their
      ocular condition (mean time tradeoff score = 0.77-0.8) and that laser
      photocoagulation can improve health-related quality of life (significant
      improvement noted in 8 of 11 domains in the National Eye Institute Visual
      Function Questionnaire). In addition, recent research has noted that health
      related quality of life can become affected in persons with diabetic retinopathy
      prior to visual loss, primarily because of anxiety about the future and emotional
      reaction to diagnosis and treatment. SUMMARY: From a search of the literature,
      several recent articles could be identified that demonstrated both a qualitative
      and a quantitative reduction in health-related quality of life in persons with
      diabetic retinopathy. With many novel treatments being explored for the
      management of diabetic retinopathy and diabetic macular edema, measuring health
      related quality of life will likely play an important role both in the decision
      to offer treatment and in monitoring relevant health gains that may be derived
      from intervention.

PMID- 15870572
TI  - New and classic insights into presumed ocular histoplasmosis syndrome and its
      treatment.
AB  - PURPOSE OF REVIEW: Presumed ocular histoplasmosis syndrome classically presents
      with atrophic choroidal scars, which are thought to progress into choroidal
      neovascularization in a small proportion of patients. The pathophysiology of the
      disease, including its underlying etiology, continues to be controversial and
      subject to ongoing research. Even more important is the controversy that
      surrounds the optimal treatment for choroidal neovascularization in patients with
      presumed ocular histoplasmosis, in particular that of subfoveal localization.
      RECENT DEVELOPMENTS: Intense efforts oriented toward defining the most beneficial
      therapeutic modality have resulted in some well-designed, large studies that
      evaluated submacular surgery, photodynamic therapies, and anti-angiogenic
      therapies, as well as small pilot studies exploring new therapeutic approaches
      for choroidal neovascularization. SUMMARY: Important results obtained by these
      studies were recently made public, and the conclusions that may be drawn from
      them, as well as an update on findings concerning presumed ocular histoplasmosis
      etiology, epidemiology, and pathophysiology are presented in this report.

PMID- 15870573
TI  - Light energy, cataract surgery, and progression of age-related macular
      degeneration.
AB  - PURPOSE OF REVIEW: Some studies suggest an association between light exposure and
      increased risk of advanced age-related macular degeneration. The natural lens
      serves as a barrier to some of the higher energy light rays. There is some
      concern that cataract surgery may be contributing to the increase in prevalence
      of age-related macular degeneration. RECENT FINDINGS: It has been shown that blue
      light absorption by retinal pigment epithelium results in free radical formation,
      leading to cellular injury, and that blue filters can reduce this rate of cell
      death. Other studies have shown a tendency for pseudophakic eyes to progress to
      the wet form of age-related macular degeneration more so than their fellow eyes.
      SUMMARY: Currently there is no conclusive evidence to support a relation between
      progression of age-related macular degeneration and cataract surgery. Given that
      nearly two million cataract extractions are performed yearly, a large randomized
      controlled study is required to prove or disprove the ability of tinted
      intraocular lenses to aid in preventing the progression of age-related macular
      degeneration.

PMID- 15870574
TI  - Update on treatment strategies for bleb-associated endophthalmitis.
AB  - PURPOSE OF REVIEW: Visual preservation in the setting of bleb-associated
      endophthalmitis has been difficult with existing management strategies. In this
      article, established findings are compared and potential new treatments that may
      improve visual outcomes in bleb-associated endophthalmitis are evaluated. RECENT
      FINDINGS: Recent reports have contributed to the existing database of results
      from bleb-associated endophthalmitis. New systemic antibiotics and novel surgical
      techniques are also described. SUMMARY: More options are now available to treat
      bleb-associated endophthalmitis. No one treatment paradigm is definitively
      superior in producing desired visual outcomes.

PMID- 15870575
TI  - The risk of fellow eyes in patients with rhegmatogenous retinal detachment.
AB  - PURPOSE OF REVIEW: A review of the current literature regarding the risk of
      nontraumatic rhegmatogenous retinal detachment in the fellow eye and prophylaxis
      of predisposing lesions is presented. RECENT FINDINGS: Although reports vary in
      study design and inclusion/exclusion criteria, the risk of retinal detachment in
      fellow eyes is similar to prior findings. Studies on prophylactic therapy also
      treated different cohorts. This makes drawing definitive conclusions difficult.
      SUMMARY: Rhegmatogenous retinal detachment poses a significant threat to the
      fellow eye. Risk factors specifically relevant to the fellow eye are discussed.
      There is insufficient evidence to recommend prophylactic therapy for prevention
      of retinal detachment in the fellow eye. To date, no prospective, randomized
      clinical trial on the prevention of retinal detachment in the fellow eye has been
      published.

PMID- 15870576
TI  - Self-reported visual functioning and quality of life in age-related macular
      degeneration.
AB  - PURPOSE OF REVIEW: To review the current literature on the impact of age-related
      macular degeneration on self-reported visual functioning, quality of life, and
      independent living. RECENT FINDINGS: The quantitative relationships between
      visual acuity, an objective clinical measure of vision, and self-reported visual
      functioning have been explored and described within prospective longitudinal
      clinical trials. When age-related macular degeneration is bilateral, the severe
      and irreversible loss of central vision experienced by affected persons has been
      shown to result in despondency, inability to care for self or others, and a state
      of disutility, which is equivalent to that experienced in coronary heart disease
      and stroke. SUMMARY: Quality-of-life indicators and self-reported visual
      functioning have gained acceptance as key outcome measure in studies designed to
      test therapeutic interventions and rehabilitation strategies in age-related
      macular degeneration. Vision loss from age-related macular degeneration engenders
      a profound sense of loss and the resultant handicap has been likened to that of
      the most severe medical conditions.

PMID- 15870577
TI  - The macroeconomics of vitreoretinal diseases.
AB  - PURPOSE OF REVIEW: The purpose of this review is to examine the macroeconomics of
      vitreoretinal diseases. RECENT FINDINGS: Approximately 6% of the Medicare Part B
      expenditure was spent on ocular diseases and 0.3% on vitreoretinal interventions.
      Among the 17,674 practicing ophthalmologists, 1849 (10.5%) designated themselves
      as specializing in the treatment of vitreoretinal diseases. Ophthalmologists
      receive 38% of their payments from Medicare; 13% of their total income were
      capitated. Age-related macular degeneration and diabetic retinopathy, two
      conditions commonly treated by vitreoretinal specialists, are projected to affect
      more than 10 million people in 2020. SUMMARY: Vitreoretinal interventions account
      for only a small portion of the total health care expenditure. The rising demand
      from the aging population and health care costs will continue to put pressure on
      all physicians and society. The changes in the sources of payment and managed
      care will directly affect the economics of a physician's practice.

PMID- 15870578
TI  - How to interpret a healthcare economic analysis.
AB  - PURPOSE: The purpose of the review is to present guidelines to help the clinician
      to interpret healthcare economic analyses and review pertinent recent analysis in
      the ophthalmic literature. RECENT FINDINGS: There are four variants of healthcare
      economic analyses: (1) cost-minimization analysis; (2) cost-benefit analysis; (3)
      cost-effectiveness analysis and (4) cost-utility analysis. Cost-utility utility
      analysis has assumed an increasingly important role in healthcare, with
      increasing number of analyses occurring in the peer-reviewed ophthalmic
      literature. These include cost-utility analyses of cataract surgery in the first
      and second eyes, amblyopia treatment, and cost-utility analyses encompassing the
      vitreoretinal interventions of the following: (1) laser photocoagulation for
      exudative macular degeneration; (2) laser treatment for diabetic retinopathy; (3)
      laser photocoagulation for branch retinal vein obstruction; (4) diabetic
      vitrectomy; (5) treatment of proliferative retinopathy of prematurity and (6)
      treatment of retinal detachment associated with proliferative vitreoretinopathy.
      As an increasing number of cost-utility analyses become available they will
      provide the information system for the practice of value-based medicine, or
      medicine based upon the patient-perceived value conferred by interventions.
      SUMMARY: Increasing numbers of cost-utility analysis in the ophthalmic literature
      suggest that ophthalmic interventions, including vitreoretinal interventions, are
      cost effective. Cost-utility analysis is a major tool in value-based medicine,
      the practice of medicine based upon the patient-perceived value conferred by
      healthcare interventions.

PMID- 15870579
TI  - Bibliography. Current world literature.

PMID- 15870584
TI  - Coronary artery calcium in HIV-infected men treated with highly active
      antiretroviral therapy.
AB  - Calcium is a common component of an atherosclerotic plaque; therefore, the
      presence of coronary artery calcium (CAC) indicates atherosclerosis. This study
      investigated the difference in total CAC scores between HIV-infected patients
      treated with highly active antiretroviral therapy (HAART) and HIV-negative age
      matched controls. HIV patients were 27 men treated with a protease inhibitor
      containing HAART regimen for more than 1 year (M = 4.92 years, SD = 2.02), aged
      30 to 60 years (M = 43.52 years, SD = 6.65), and not receiving lipid-lowering or
      hypoglycemic drugs. Controls were age-matched men randomly selected (three
      controls to one case, for a total of 81 controls) from our existing database of
      25,250 men who self-referred for CAC screening (control database). Electron beam
      tomography was used to obtain CAC scores. The CAC scores were coded as above or
      below the age-specific (stratified in 5-year increments) 10th, 25th, 50th, 75th,
      or 90th percentile of our control database. Chi-square analyses for two
      independent samples indicated (1) a larger frequency of controls with CAC scores
      above the 10th (chi1= 8.32, P = .004) and 25th (chi1= 5.45, P = .02) percentiles
      than that of HIV patients, (2) no differences in CAC scores between groups above
      the 50th (chi = 0.85, P = .357) or 75th (chi = 0.46, P = .497) percentile, and
      (3) a larger frequency of HIV patients who were above the 90th percentile (chi =
      4.5, P = .034). The strength of the relationship between group membership and
      scoring above the 90th percentile was significant (phi = 0.20, P = .034). These
      results tentatively suggest that there is an elevated level of subclinical
      atherosclerosis in HIV patients treated with HAART.

PMID- 15870585
TI  - Cardiovascular disease research in Native Americans.
AB  - Even though Native Americans have greater risk factors, prevalence, and mortality
      rates for cardiovascular disease when compared with some other races, these
      health disparities are poorly addressed in research studies, particularly in
      nursing research. To better understand these issues, the epidemiology of
      cardiovascular disease in Native Americans is presented. Selected cardiovascular
      diseases are discussed, including hypertension, coronary artery disease, and
      stroke. Governmental, socioeconomic, and cultural influences are explored. A
      synthesis of related research is provided along with a description of the gaps
      that remain to be addressed.

PMID- 15870586
TI  - The importance and impact of social support on outcomes in patients with heart
      failure: an overview of the literature.
AB  - As advances in medical treatment of heart failure (HF) become limited, other
      factors are being studied to improve outcomes. There is much evidence that
      supportive social relations have a major impact on health outcomes and that
      social support is essential for adjustment to illness. This article describes
      current research on the influence of social support on outcomes in patients with
      HF. A computerized literature search in Medline, CINAHL, and PsychLit was
      performed on each of the different outcomes in relation to social support,
      covering the period 1993 to 2003. Seventeen studies were found that investigated
      the relationship between social support and different outcome measures in HF.
      Four studies found clear relationships between social support and
      rehospitalizations and mortality; the relationship between quality of life and
      depression was less clear. Up to now, limited research has been done on the
      impact of social support on outcomes in patients with HF. The available studies
      suggest that social support has an impact on HF outcomes but further research is
      necessary before firm conclusions about the nature of these relationships can be
      reached.

PMID- 15870587
TI  - Women's perceptions of coronary heart disease: an integrative review.
AB  - Coronary heart disease (CHD) is the leading cause of death in American women and
      is a major cause of morbidity. The American Heart Association (AHA) reports that
      in the year 2000, 515,661 women died from all categories of cardiovascular
      disease. An estimated 254,630 women suffer a myocardial infarction annually.
      Women diagnosed with CHD experienced greater morbidity and mortality than men.
      Women's perceptions of their risk for heart disease can greatly influence their
      decision-making process in regard to healthcare decisions. The general public
      still perceives heart disease as primarily a health problem for men. Evidence
      shows that women perceive breast cancer as a greater risk than CHD. These
      misperceptions may lead women to underestimate their risk for CHD and fail to
      seek early interventions to prevent unnecessary morbidity and mortality. The
      purpose of this article is to report the results of an integrative review of
      nursing research related to women's perceptions of risks for heart disease.
      CINAHL, Medline, EBSCO host, and Proquest databases were searched for nursing
      research conducted between the years of 1985 and 2002. Key search terms were
      women, heart disease, coronary artery disease, perceptions, risk factors, and
      health promotion behaviors. Study selection was limited to the first author being
      a nurse researcher. Twenty articles and dissertations were retrieved that met the
      key search terms. Eleven articles were excluded because the first author was not
      a nurse researcher. This integrative review includes 5 articles and 4
      dissertations. Results revealed that women's perceptions of their CHD risks are
      underestimated, that health-promoting behaviors are not influenced by risk
      perceptions, that society imposes barriers that prevent participation in health
      promotion behavior, and that communication between women and their healthcare
      providers is lacking.

PMID- 15870589
TI  - Heart rate variability analysis in the assessment of autonomic function in heart
      failure.
AB  - Heart rate is not static, but rather changes continuously in response to physical
      and mental demands. In fact, an invariant heart rate is associated with disease
      processes such as heart failure. Heart rate variability analysis is a noninvasive
      technique used to quantify fluctuations in heart rate. In this article, the
      authors review neural control of heart rate, briefly describe heart rate
      variability, and summarize research data demonstrating that heart failure is
      associated with altered heart rate variability. In addition, the authors present
      evidence that heart failure patients with decreased heart rate variability are at
      risk for future cardiac events, heart transplantations, and death.

PMID- 15870588
TI  - Cardiovascular training effect associated with polestriding exercise in patients
      with peripheral arterial disease.
AB  - Because individuals with claudication pain secondary to peripheral arterial
      disease (PAD) are limited in both walking speed and duration, the benefits of
      walking exercise may be insufficient to yield a cardiovascular training effect.
      The objectives of this analysis were to determine whether polestriding exercise
      training, performed by persons with PAD, would improve exercise endurance, elicit
      a cardiovascular training benefit, and improve quality of life (QoL). Persons (n
      = 49) whose claudication pain limited their exercise capacity were randomized
      into a 24-week polestriding training program (n = 25, 65.8 +/- 7.1 years of age)
      or a nonexercise attention control group (n = 24, 68.0 +/- 8.6 years of age).
      Those assigned to the polestriding group trained 3 times weekly. Control group
      subjects came to the laboratory biweekly for ankle blood pressure measurements. A
      symptom-limited ramp treadmill test, ratings of perceived leg pain, and QoL data
      (using the Short Form-36) were obtained at baseline and upon completion of
      training. After 24 weeks of polestriding training, subjects increased their
      exercise endurance from 10.3 +/- 4.1 minute to 15.1 +/- 4.5 minute. This was
      significantly greater than control group subjects whose exercise endurance
      declined (from 11.2 +/- 4.7 to 10.3 +/- 4.7 minute; P < .001). Relationships
      between systolic blood pressure (P < .001), heart rate (P = .04), rate pressure
      product (P = .05), oxygen uptake (P = .016), and perceived leg pain (P = .02) and
      exercise time improved from the baseline symptom-limited treadmill test to the 6
      month symptom-limited treadmill test in the polestriding group compared to the
      control group. The improvement in the physical component summary score of the
      Short Form-36 was also greater in the polestriding group (P = .031). Polestriding
      training significantly improved the clinical indicators of cardiovascular fitness
      and QoL, and decreased symptoms of claudication pain during exertion.

PMID- 15870591
TI  - Biofeedback-assisted relaxation training for essential hypertension: who is most
      likely to benefit?
AB  - The main purpose of this study was to develop a way to predict which persons with
      essential hypertension would benefit most from biofeedback-assisted relaxation
      (BFAR) training. Second, the authors evaluated the effect of BFAR on blood
      pressure (BP) reduction, which was measured in the clinic and outside the clinic
      using an ambulatory BP monitor. Fifty-four adults with stage 1 or 2 hypertension
      (78% taking BP medications) received 8 weeks of relaxation training coupled with
      thermal, electromyographic, and respiratory sinus arrhythmia biofeedback. Blood
      pressure was measured in the clinic and over 24 hours using an ambulatory BP
      monitor pretraining and posttraining. Systolic BP dropped from 135.0 +/- 9.8 mmHg
      pretraining to 132.2 +/- 10.5 mmHg posttraining (F = 6.139, P = .017). Diastolic
      BP dropped from 80.4 +/- 8.1 mmHg pretraining to 78.5 +/- 10.0 mmHg posttraining
      (F = 4.441, P = .041). Data from 37 participants with baseline BP of 130/85 mmHg
      or greater were used to develop a prediction model. Regression showed that those
      who were able to lower their SBP 5 mm Hg or more were (1) not taking
      antihypertensive medication, (2) had lowest starting finger temperature, (3) had
      the smallest standard deviation in daytime mean arterial pressure, and (4) the
      lowest score on the Multidimensional Health Locus of Control-internal scale.
      Since these types of persons are most likely to benefit from BFAR, they should be
      offered BFAR prior to starting hypertensive medications.

PMID- 15870592
TI  - What is the perceived quality of life of adults with congenital heart disease and
      does it differ by anomaly?
AB  - Adults with congenital heart disease (CHD) represent a growing population of
      patients thanks to the medical and surgical advances which enable at least 85% of
      children to survive to adulthood. These advances may create quality-of-life (QoL)
      issues not previously considered. The purpose of this cross-sectional study of
      124 adults with CHD was to describe their QoL as a basis for providing
      appropriate information, counseling, and anticipatory guidance. Thirteen patients
      had single ventricle physiology (SVP), 43 had cyanotic lesions with 2 ventricle
      repairs, and 68 had acyanotic CHD. On the basis of Sickness Impact Profile (SIP)
      scores, individuals with SVP had worse QoL than did those with cyanotic lesions
      (with 2 ventricle repairs) and acyanotic anomalies (SIP = 9.98 vs 4.61 and 3.76).
      SIP scores were statistically significantly different between those with SVP and
      those with acyanotic anomalies (P = .02). For all groups, the areas of life most
      affected were work and sleep and rest. Participants with SVP saw themselves as
      having the poorest QoL.

PMID- 15870593
TI  - Nurses' knowledge of heart failure education topics as reported in a small
      midwestern community hospital.
AB  - Recurrent heart failure (HF) is the most common cause for readmission of elderly
      patients with HF. Patient education is an essential component of care for these
      patients. Healthcare providers must have a sufficient knowledge base to
      facilitate this education. This study aims to describe nurses' knowledge of HF
      self-management education principles. Fifty-one nurses working in a small
      Midwestern community hospital completed a 20-item true or false written survey
      developed by Albert et al (Heart Lung. 2002;31:102-112) to assess their knowledge
      of 5 areas of HF self-management. The sample included 14 nurses working in an
      intensive care unit and 41 nurses working on a general medical unit, all
      routinely providing care to patients with HF. The mean (+/-SD) HF self-care
      knowledge score was 14.6 +/- 2 (range = 9-19). There was no statistical
      difference in mean score between intensive care unit (14.7 +/- 1.6) and floor
      (14.5 +/- 2.1) nurses. Correct responses to individual survey items ranged from
      20% to 100%; 6 questions resulted in mean scores >90% correct, 9 questions had
      mean scores between 70% and 90% correct, and 5 questions had mean scores <70%
      correct. Most respondents (90%) answered 6 questions correctly, but on 9
      questions, 70% and 90% answered correctly. On 5 questions, less than 70% answered
      them correctly. Two questions (need for daily weight monitoring when asymptomatic
      and the importance of notifying the doctor of new onset or worsening of fatigue)
      were answered correctly by all participants. Subject areas of frequently missed
      questions were the use of nonsteroidal anti-inflammatory drugs, use of potassium
      based salt substitutes, assessment of weight results, and physician notification
      of asymptomatic low blood pressure and momentary dizziness when rising. These
      results suggest that nurses working in a small community hospital may not be
      sufficiently knowledgeable in HF management principles. Additional emphasis on HF
      educational principles may improve the quality of patient education. One
      suggested intervention is to provide ongoing education for nurses regarding HF
      management.

PMID- 15870595
TI  - Collaborative initiatives in CVD prevention.

PMID- 15870596
TI  - Oculocerebral syndrome of Lowe.

PMID- 15870597
TI  - Glaucoma with the oculocerebrorenal syndrome of Lowe.
AB  - PURPOSE: To further describe the glaucoma with the oculocerebrorenal syndrome of
      Lowe (OCRL) including the responsible filtration angle abnormalities and response
      to treatment. METHODS: The scientific literature regarding the glaucoma
      associated with OCRL from 1952, when the first report of the syndrome appeared,
      to the present was reviewed. The medical records of 7 patients with OCRL were
      studied. The occurrence of glaucoma, corneal changes secondary to glaucoma,
      gonioscopic abnormalities, iris features, and response to glaucoma surgery were
      recorded. RESULTS: Signs of glaucoma are defining abnormalities leading to
      recognition of OCRL. The OCRL medical literature reports the frequency of
      glaucoma, secondary clinical signs of increased intraocular pressure (IOP), and
      results of glaucoma surgery, but little information related to the responsible
      filtration angle abnormalities. Glaucoma was present in 71% (5 of 7) of patients
      studied, and was recognized in infancy in 9 of their 10 eyes. Gonioscopy was
      performed in 6 OCRL patients and revealed the constant presence of open angles,
      primary filtration angle anomalies, and defects considered secondary to previous
      infantile lens extractions. The observed anomalies were anterior insertion of the
      iris, narrowing of the ciliary body band, and decreased visibility of the scleral
      spur. The angle defects felt to be acquired following lens surgery included a
      more anterior insertion of the iris on to the trabecular meshwork, pigment
      dusting of the angle tissues, and iris synechial abnormalities related to the
      surgery. Bilateral goniotomies were unsuccessful in 4 of 4 patients. The fundi of
      6 of 7 patients showed normal optic disc development with variable abnormalities
      secondary to glaucoma, and normal retinal vessels. Minimal evidence of macular
      development was observed in a single patient from 1 month of age to his most
      recent examination at 14 months of age. CONCLUSION: A primary X-linked infantile
      glaucoma is a defining and frequent component of OCRL and is secondary to
      expression of a primary filtration angle anomaly. Goniotomy was unsuccessful in
      all (8) operated eyes. The adverse effects of cataract surgery on the filtration
      angle structures may influence the results of goniotomy surgery by superimposing
      a secondary aphakic glaucoma component that may explain the need for alternative
      glaucoma surgery.

PMID- 15870598
TI  - Phacoemulsification and goniosynechialysis in the management of unresponsive
      primary angle closure.
AB  - PURPOSE: To evaluate the effectiveness of phacoemulsification and
      goniosynechialysis (PEGS) in managing acute and subacute primary angle closure
      unresponsive to conventional therapy. MATERIALS AND METHODS: Retrospective series
      of patients of six glaucoma-trained surgeons with primary angle closure that did
      not respond to medical management, Nd:YAG laser peripheral iridotomy, or argon
      laser peripheral iridoplasty. RESULTS: A total of twenty-one patients with an
      average age of 65.6 years were included. Underlying mechanism of angle closure
      included pupillary block (n = 18) and plateau iris (n = 3). Average intraocular
      pressure (IOP) immediately prior to PEGS was 40.7 mm Hg, and mean follow-up time
      after PEGS was 11.7 months. PEGS decreased mean IOP by 25 mm Hg (62%), and mean
      number of medications from 3.8 pre-surgery to 1.7 post-surgery (55%). Mean LogMar
      visual acuity improved after PEGS, from 0.64 to 0.44 (Paired t test t = 4.120 P =
      0.001). Subsequent trabeculectomy was necessary in one case (5%). CONCLUSIONS:
      Phacoemulsification with goniosynechialysis may be an effective treatment option
      for primary angle closure unresponsive to conventional therapy.

PMID- 15870599
TI  - Quality of controlled clinical trials on glaucoma and intraocular high pressure.
AB  - AIM: To study the quality of controlled clinical trials on glaucoma. METHODS: Two
      hundred and twenty-six clinical trials published between 1980 and 1999 were
      selected from seven international ophthalmological journals. Their quality was
      assessed by four researchers with epidemiological skills using a structured
      questionnaire. RESULTS: Sample size was pre-estimated in 34 (15.0%) papers, which
      were of greater size (P = 0.05). Randomization was performed in 98.2% of the
      trials, although the procedure of randomization was scarcely reported. Masking
      was reported in 56.6% of the papers, and was more frequent in medical treatments
      (P < 0.001). The basal characteristics of the groups were compared in 139 papers
      (61.5%). Patient losses during the follow-up period were fully described in only
      27 trials. Intention-to-treat analysis was used in 17 (7.7%) papers. Most trials
      reported P values, but a measure of effect (mean, proportion, or relative risk)
      appeared in only 16 trials (7.7%). Trials performed in the US more frequently
      compared baseline characteristics of the groups (P = 0.03), described the patient
      flow (P = 0.04), and used adequate statistical procedures (P = 0.03). Those
      trials that included a statistician or an epidemiologist among the authors were
      more commonly blinded (P = 0.06) and they always avoided the analyses of
      subgroups (P = 0.006). Several methodological issues have improved throughout the
      studied period. CONCLUSIONS: Several methodological characteristics should be
      improved when reporting a clinical trial on glaucoma. Using a checklist like that
      suggested by the CONSORT can help to achieve this.

PMID- 15870600
TI  - Sequential office pressure measurements in the management of glaucoma.
AB  - PURPOSE: To evaluate the usefulness of day-long sequential office measurements of
      intraocular pressure (IOP) to make therapeutic decisions in patients with
      progressive glaucomatous damage despite apparently 'controlled' IOP. METHODS: We
      reviewed the records of 93 consecutive glaucoma patients (185 eyes) who underwent
      sequential office IOP measurements (every hour from 7 AM to 5 PM on a single
      day). These included 53 patients with normal-tension glaucoma (NTG), 12 glaucoma
      suspects (GS), and 28 patients with primary open-angle glaucoma (POAG) whose
      visual field deteriorated despite apparently 'controlled' IOP. Only one eye per
      patient was included in the study. RESULTS: The pattern of the day-long IOP curve
      was similar in the 3 groups of patients. IOPs were highest in the early morning
      hours in all groups. The mean +/- SD of the IOP range was 5 +/- 2 mm Hg. An IOP >
      21 mm Hg was found in 3 eyes (3%), whereas a range of IOPs > 5 mm Hg was detected
      in 33 eyes (35%). In the NTG group, there was a significant correlation between
      visual field deterioration and the peak and range of IOP (P = 0.0002 and P =
      0.05, respectively). CONCLUSIONS: Day-long sequential office IOP measurements are
      useful in selected patients who demonstrate progressive glaucomatous damage.
      Early morning measurements are most frequently highest. The range of IOP may be
      as important, or more important than, the peak IOP level.

PMID- 15870601
TI  - Measurement of intraocular pressure using the NT-4000: a new non-contact
      tonometer equipped with pulse synchronous measurement function.
AB  - PURPOSE: NT-4000 (Nidek Co. Ltd., Gamagori, Japan) is a new non-contact tonometer
      (NCT) equipped with pulse synchronous measurement function that can measure
      intraocular pressure (IOP) synchronized with the ocular pulse. The purpose of
      this study was to evaluate the usefulness of NT-4000 in normal subjects and in
      patients with glaucoma and ocular hypertension. METHODS: This study included 175
      eyes of 175 subjects. Firstly, the IOP was measured using NT-4000 without the
      pulse synchronous measurement function (NTn). Secondly, the IOP at peak, middle,
      and trough phases of the pulse signal were measured using NT-4000 with the pulse
      synchronous measurement function (NTp, NTm, NTt, respectively). Additionally, the
      IOP was measured with Goldmann applanation tonometer (GT). The coefficient of
      variation (CV) of three readings in the NCT measurements was used to evaluate the
      intra-session reproducibility. Statistical comparisons were performed using
      Wilcoxon signed rank test and one-way analysis of variance with Scheffe's test.
      Linear regression analysis was used to calculate correlation coefficients. P
      values less than 0.05 were accepted as statistically significant. RESULTS: The CV
      of NTn, NTp, NTm, and NTt were 6.4%, 5.5%, 4.9%, and 5.2%, respectively. The CV
      of NTp, NTm, and NTt were significantly smaller than that of NTn (P = 0.007, P <
      0.001, P < 0.001, respectively). NTp was significantly higher than NTt (P =
      0.038). GT was significantly correlated with NTn, NTp, NTm, and NTt (r = 0.898, P
      < 0.001; r = 0.912, P < 0.001; r = 0.908, P < 0.001; r = 0.900, P < 0.001,
      respectively). CONCLUSION: NT-4000 can detect the fluctuation of IOP associated
      with the ocular pulse.

PMID- 15870602
TI  - Ratio of hemi-papillary rim volumes and glaucoma diagnosis with Heidelberg retina
      tomograph.
AB  - PURPOSE: To test if inclusions of the ratios of hemi-papillary parameters in the
      discriminant function could improve the precision in glaucoma diagnosis with the
      Heidelberg Retina Tomograph (HRT). MATERIALS AND METHODS: Papillary topographs
      obtained with HRT were reviewed in 202 patients with primary open angle glaucoma,
      exfoliation glaucoma, pigment glaucoma, ocular hypertension, or glaucoma
      heredity. A hemi-papillary HRT parameter was obtained by horizontally dividing
      the optic nerve head image into two halves. A ratio was calculated for each of
      the HRT parameters with the greater value of the two halves as numerator. The
      hemi-papillary HRT parameters, together with the ordinary HRT papillary
      parameters, were evaluated with discriminant analysis to estimate their
      significance in the glaucoma diagnosis. RESULTS: The new discriminant function
      is: the ratio of hemi-papillary rim volumes * 1.110 + cup/disc area ratio * 2.560
      + rim area * -1.674 -0.040, established in a group of 66 eyes. The sensitivity of
      this discriminant function was 84.0%, and the specificity 92.7% in this group.
      When this discriminant function was applied to a test group of 74 eyes the
      sensitivity was 89.2% and specificity 87.0%. The sensitivity with the new
      discriminant function was 81.8% at the early stage of glaucoma and 100.0% at
      moderate or advanced glaucoma damage. CONCLUSION: The new discriminant function,
      including the ratio of hemi-papillary rim volumes, the total rim area, and the
      cup-disc area ratio improves the precision in glaucoma diagnosis with HRT.

PMID- 15870603
TI  - Evaluation of the influence of tilt of optic disc on the measurement of optic
      disc variables obtained by optical coherence tomography and confocal scanning
      laser ophthalmoscopy.
AB  - PURPOSE: To evaluate the relationship between optic disc variables measured by
      confocal scanning laser ophthalmoscopy (CSLO) and optical coherence tomography
      (OCT). METHODS: Fifty-one eyes in 27 non-glaucomatous patients were scanned using
      a CSLO-TopSStrade mark and an OCT-OCT 3000trade mark. The relationship between
      the following four optic disc variables-disc area (DA), cup area (CA),
      neuroretinal rim area (NRRA), and cup-disc area ratio (CDAR)-measured by CSLO and
      OCT were evaluated, and the relationship between these measurements and optic
      disc tilt was assessed. Horizontal (HD) and vertical diameters (VD) of the optic
      disc were measured from disc photographs, and by CSLO and OCT, and ratios (HD/VD)
      were then compared. RESULTS: There was a good correlation in DA, CA, and CDAR
      except NRRA between OCT and CSLO measurements. In eyes with a tilt >/=4 degrees,
      DA and NRRA were measured larger, and CDAR and CA were measured smaller by OCT
      than by CSLO. However, in the eyes with a tilt of <4 degrees, no significant
      differences in measurement of disc variables were observed for the two
      measurement systems. HD/VD measured from disc photographs was well correlated
      with those determined by CSLO (r = 0.741, P < 0.0001), however, it correlated
      poorly with those measured by OCT in whole study eyes (r = 0.410, P = 0.008) and
      in eyes tilted by >/=4 degrees, respectively (P = 0.280). CONCLUSIONS: Although
      CSLO and OCT measurements of the optic disc are highly correlated, discrepancy
      becomes prominent in eyes with a disc tilted >/=4 degrees. Therefore, analysis of
      the optic nerve head by OCT must be cautiously interpreted in eyes with a highly
      tilted disc.

PMID- 15870604
TI  - Frequency of goldmann applanation tonometer calibration error checks.
AB  - PURPOSE: To investigate how quickly Goldmann applanation tonometers used in
      clinical practice develop calibration errors, and to determine the frequency of
      checks required to detect these errors. MATERIALS AND METHODS: Prospective check
      of the calibration error of all Haag-Streit Goldmann applanation tonometers in
      the department at month zero, month one, and month four. The tonometers were
      checked according to the Haag-Streit method using a standard calibration check
      weight bar by two independent observers. Calibration errors were classed as +/
      0.5 to 2.5 mm Hg, +/-3 to 4 mm Hg, or >+/-4 mm Hg. Tonometers with a calibration
      error greater than +/-2.5 mm Hg were returned to the manufacturer for re
      calibration. RESULTS: At month zero 2 of 34 (5.9%), at month one 3 of 29 (10.3%),
      and at month four 0 of 33 (0.0%) tonometers fell within the manufacturer's
      recommended calibration range of +/-0.5 mm Hg. A total of 14 of 34 (41.2%)
      tonometers at month zero, 10 of 29 (34.5%) tonometers at month one, and 17 of 33
      (51.5%) tonometers at month four were identified to have calibration errors
      greater than +/-2.5 mm Hg. CONCLUSIONS: Goldmann applanation tonometers are not
      as accurate as the manufacturer's recommended calibration error tolerance of +/
      0.5 mm Hg would suggest. Calibration error of less than +/-2.5 mm Hg is
      clinically acceptable. Calibration error checks should be carried out once
      monthly and tonometers with calibration error greater than +/-2.5 mm Hg returned
      to the manufacturer for re-calibration. Additional checks should be made if
      tonometers suffer specific damage. Ideally individual ophthalmologists should
      check calibration before each session.

PMID- 15870605
TI  - Resident glaucoma surgical training in United States residency programs.
AB  - PURPOSE: To determine current trends in resident glaucoma surgical training
      throughout the United States. METHODS: A comprehensive survey was sent to the
      residency director of all 121 ACGME-accredited ophthalmology training programs in
      the United States. RESULTS: The mean and median number of glaucoma procedures a
      resident will complete by the end of their training is 8.6 and 8 respectively for
      trabeculectomy, 5.3 and 4 for combined trabeculectomy/phacoemulsification, and
      3.6 and 2 for tube-shunts. One percent of residents will gain experience as
      primary surgeon on trabeculectomies during their first year, 32% during their
      second year, and 67% during their third year. Seventy-five percent of residents
      are taught more than one trabeculectomy technique by more than one staff surgeon.
      Eighty-four percent of residents are taught glaucoma surgery almost exclusively
      by fellowship-trained glaucoma surgeons. Eighty-two percent of residents use
      antimetabolites (mitomycin C or 5-FU) as an adjunct to trabeculectomy most or all
      of the time. More than 96% of resident tube-shunt procedures use Ahmed,
      Baerveldt, or Molteno devices. Eighty percent of residents do not perform any
      pediatric glaucoma surgeries. Sixty-two percent of residents rotate out of their
      main facility to perform glaucoma surgery. CONCLUSIONS: Residents are being
      exposed to glaucoma surgery early in their residency training. Most are
      performing a variety of different procedures and techniques, and are taught by
      fellowship-trained surgeons. Residents gain very little exposure to pediatric
      glaucoma surgery. All programs reported compliance with minimum RRC requirements
      for glaucoma filtering surgery.

PMID- 15870606
TI  - Does the adjunctive peeling of juxtacanalicular tissue affect the outcome of two
      site phaco-viscocanalostomy?
AB  - PURPOSE: To compare the surgical outcomes of combined corneal-incision cataract
      surgery and viscocanalostomy (phaco-VCS) with or without the adjunctive peeling
      of juxtacanalicular tissue (JCT) in 136 patients of open-angle glaucoma or ocular
      hypertension. METHODS: In a prospective clinical trial, 63 eyes underwent phaco
      VCS (Peeling (-) group), and 73 eyes underwent phaco-VCS with the peeling of JCT
      (Peeling (+) group). The postoperative IOP, the probability of successful IOP
      reduction without medications, and postoperative complications were compared
      between the two groups. RESULTS: The mean preoperative IOP of 19.9 +/- 3.3 (+/
      SD) mm Hg in the Peeling (-) group decreased significantly to 13.9 +/- 6.8 at 3
      days, 14.6 +/- 3.1 at 12 months, and 15.5 +/- 2.3 mm Hg at 24 months. The IOP of
      20.2 +/- 3.2 mm Hg in the Peeling (+) group decreased significantly to 11.4 +/-
      5.1 at 3 days, 14.9 +/- 3.0 at 12 months, and 15.9 +/- 2.1 mm Hg at 24 months.
      There was no significant difference in IOP levels between the two groups (P >/=
      0.1512) except for the IOP level at 3 postoperative days (P = 0.0265). The
      probabilities of achieving IOPs without medications under 21 mm Hg and 15 mm Hg
      at 24 months in the Peeling (-) groups were 61.0% and 10.4%, and those in the
      Peeling (+) group were 61.7% and 23.9% (P >/= 0.4389). The incidences of IOP
      spike more than 30 mm Hg (7.9%) and fibrin formation (15.8%) in the Peeling (-)
      group were higher than in the Peeling (+) group (0%; P = 0.0195, 5.5%; P =
      0.1907). Slit-lamp microscopic hyphema, which included red blood cells in the
      anterior chamber was observed in about half, and bleb formation more than 1 month
      was less than 5% in both groups. CONCLUSION: Postoperative IOPs were
      significantly decreased in both groups. Although the peeling of JCT was not
      enhanced in long-term reduction of the IOP, it lowered IOP at postoperative 3
      days and the incidence of IOP spike. The adjunctive procedure would be beneficial
      to glaucoma patients in phaco-VCS.

PMID- 15870607
TI  - Reconstitution of trabecular meshwork GAGs: influence of hyaluronic acid and
      chondroitin sulfate on flow rates.
AB  - PURPOSE: This study was undertaken to determine whether the concentration of
      hyaluronic acid (HA) and of chondroitin sulfate (CS) occurring in the normal and
      the primary open-angle glaucoma (POAG) trabecular meshwork (TM) influences flow
      rates in vitro as a function of pressure. METHODS: We tested 100, 500, and 4000
      kDa molecular weight HA, CS, reconstituted normal and POAG TM HA-CS and
      juxtacanalicular connective tissue (JCT) HA-CS in a micro test chamber to
      determine initial and steady-state flow rates. The resistance and permeability
      (Ko) were calculated; Linear Newtonian mechanics were used to determine the
      possible contributions of the hydrophobic interactions of HA. RESULTS: Initial
      flow rates increased in the pressure range of 5 to 20 mm Hg for the three HA
      preparations and the flow rates declined in the pressure range of 20 to 40 mm Hg.
      Flow rates of reconstituted normal TM and JCT were optimum at 10 mm Hg and then
      declined with increasing pressure. Flow rates of reconstituted POAG TM and JCT
      were optimum only at 5 mm Hg and then declined. The steady-state rate of POAG JCT
      HA-CS at 10 mm Hg was slow: the transition time (ie, the time required to start
      an increase in flow rate) was 29 hours and the lag time (ie, the time required to
      obtain steady-state flow rate) was 17 hours. The maximum flow rate in POAG JCT HA
      CS decreased by 37.2% from the normal JCT HA-CS. The calculated resistance of
      reconstituted POAG JCT HA-CS was approximately 18% of the total resistance of the
      human JCT compared with 10% in the normal JCT. CONCLUSIONS: Hyaluronic acid and
      CS contribute to flow resistance and influence flow rate in vitro. The influence
      of HA is particularly sensitive to an increase in the pressure gradient, which
      may be caused by unfolding of the hydrophobic interactions of HA polymers that
      further entangles the HA polymer. The POAG JCT HA-CS concentrations represent a
      significant factor in outflow resistance in POAG, particularly at higher
      pressures.

PMID- 15870608
TI  - The impact of a nationwide introduction of new drugs and a treatment protocol for
      glaucoma on the number of glaucoma surgeries.
AB  - PURPOSE: To study the trend in number of glaucoma surgeries, and the influence
      hereon of the introduction of new glaucoma medication, reimbursement of its
      costs, and the introduction of a treatment protocol. METHODS: Out of the Dutch
      Health Care Registration, all open angle glaucoma and ocular hypertension
      patients aged 20 years and older, who underwent glaucoma surgery were selected.
      Over the period 1995 until 2003 the trend in the number of monthly performed
      glaucoma surgeries was described by LOESS spline procedure. RESULTS: From 1995
      until 2003, 15,888 surgeries were included. Overall mean age was 67.5 years (SD
      13.0). Mean age declined by 0.29 year per year (95% CI, 0.21-0.37). In 1995 and
      1996 the number of yearly performed glaucoma surgeries was approximately 2400.
      From 1997 onwards this number started to decrease, resulting in a 45% decrease in
      the year 2000. From 2000 on the number of surgeries stabilized at approximately
      1350 per year. In 1999 the total number of prescriptions rose by 20% compared
      with 1998, and then stabilized. In 2002, 48% of the prescriptions were
      prescriptions for new medication. CONCLUSION: The number of glaucoma surgeries in
      the Netherlands almost halved over a 3.5-year period, most likely due to the
      introduction of new medications. In the remaining study period the number leveled
      off. From the present data a substitution effect and not merely a postponement of
      glaucoma surgeries may be suggested, providing additional evidence that a
      sustained reduction in the number of glaucoma surgeries was reached in the
      studied period.

PMID- 15870609
TI  - Additivity of pilocarpine to bimatoprost in ocular hypertension and early
      glaucoma.
AB  - PURPOSE: To determine if the intraocular pressure (IOP) effect of pilocarpine at
      various concentrations is additive to that of bimatoprost and to assess the
      tolerability of this combination. METHODS: This was a randomized, prospective
      trial of patients with IOP > 21 mm Hg following appropriate medication washout.
      For all visits IOP was measured at 9:00 AM and 11:00 AM. Following baseline visit
      (#1), bimatoprost 0.03% was instilled qhs OU through visit 6. Following visits 2,
      3, and 4 pilocarpine (2%, 4%, 6%) was instilled qid in one randomly selected eye.
      Pilocarpine was discontinued after visit 5 and bimatoprost after visit 6. Two
      tailed, paired t test was used to compare treated and contralateral eyes for
      their IOP, IOP change, percentage IOP change from baseline, and to compare IOP in
      the same eye at 9:00 AM and 11:00 AM (before and after pilocarpine
      administration). IOPs using bimatoprost alone or in combination with various
      pilocarpine concentrations were compared using single variant Analysis of
      Variance (ANOVA). RESULTS: Seventeen patients were enrolled and 13 patients
      completed the study. Bimatoprost reduced IOP 28.7% to 30.5% (P < 0.0001) from
      baseline to visit 2. IOPs in eyes treated with bimatoprost alone or with
      bimatoprost and various pilocarpine concentrations were similar (P > 0.81,
      ANOVA). The IOP (P > 0.17) and percentage IOP change from baseline (P > 0.10) was
      similar in treated and contralateral eyes with all three strengths of
      pilocarpine. IOP values at 9:00 AM and 11:00 AM, before and after pilocarpine
      administration, were similar (P > 0.22). CONCLUSION: Bimatoprost alone reduces
      IOP substantially. Pilocarpine added to bimatoprost at concentrations of 2%, 4%,
      or 6% was neither additive nor antagonistic to the ocular hypotensive efficacy of
      bimatoprost.

PMID- 15870610
TI  - Fluctuating intraocular pressure.

PMID- 15870611
TI  - Hope, awareness of illness, and coping in schizophrenia spectrum disorders:
      evidence of an interaction.
AB  - Controversy exists regarding whether awareness of schizophrenia is linked with
      healthier or poorer psychosocial function. This study examined whether hope might
      interact with insight to affect function at the level of active versus avoidant
      coping preferences among 96 persons with schizophrenia spectrum disorders.
      Factorial multivariate analysis of variance comparing groups classified on the
      basis of hope and insight scores revealed a significant interaction between hope
      and insight (Wilks lambda = 2.7; p< 0.05). Post hoc analyses indicated that
      persons with high insight and high hope demonstrated the most adaptive coping
      preferences, whereas those with high insight and lower hope demonstrated the
      least.

PMID- 15870612
TI  - Can older people with schizophrenia benefit from work rehabilitation?
AB  - To determine whether older people with schizophrenia or schizoaffective disorder
      can benefit from work therapy as has been shown with their younger counterparts,
      41 older patients (50+) were compared with 104 younger patients on their clinical
      and vocational outcomes while participating in a 6-month work therapy program. In
      an intent-to-treat analysis, both groups showed significant improvements in
      symptoms and quality of life at the conclusion of the active intervention, but
      there were no significant differences between age groups. In comparisons of
      biweekly Work Behavior Inventory scores for completers, older workers improved
      more than younger workers, particularly during the second half of the program.
      Results are in accord with previous evidence for the clinical and vocational
      benefits of work therapy and indicate that older people with schizophrenia or
      schizoaffective disorder can perform at least as well as their younger
      counterparts and respond similarly with improved symptoms and quality of life.

PMID- 15870613
TI  - The psychology of persecutory ideation I: a questionnaire survey.
AB  - Paranoia is a complex phenomenon that is likely to arise from a number of
      factors. In a recent cognitive model of persecutory delusions, three key factors
      are highlighted: anomalous experiences, emotion, and reasoning. In the first of
      two linked studies, we report a questionnaire survey of nonclinical paranoia
      designed to assess the theoretical model. A nonclinical population (N = 327)
      completed measures of paranoia, anomalous experiences (hallucinatory
      predisposition, perceptual anomalies), emotion (depression, anxiety, self-focus,
      stress, interpersonal sensitivity), and reasoning (need for closure). Paranoia
      was best explained by separation anxiety, depression, fragile inner self,
      hallucinatory experiences, discomfort with ambiguity, stress, self-focus,
      perceptual anomalies, and anxiety. The findings are consistent with the central
      predictions within the model of paranoia.

PMID- 15870614
TI  - The psychology of persecutory ideation II: a virtual reality experimental study.
AB  - A cognitive model of persecutory delusions is used to predict the occurrence of
      nonclinical paranoid thoughts in a virtual reality environment. Scorers across
      the range of paranoia entered a virtual reality scene populated by five computer
      characters programmed to behave neutrally (N = 30). Many appraisals of the
      computer characters were positive or neutral. However, there were also
      persecutory thoughts about the characters. Providing evidence of the validity of
      the experimental method, persecutory ideation was predicted by higher trait
      paranoia and a greater sense of presence in the environment. The psychological
      variables from the cognitive model that predicted persecutory ideation were
      anxiety, timidity, and hallucinatory predisposition. Further, hallucinatory
      predisposition distinguished the prediction of paranoid thoughts from social
      anxiety in virtual reality. It is concluded that nonclinical paranoid thoughts
      are most closely associated with emotional disturbances and anomalous
      experiences. Extreme reasoning bias may particularly contribute to the
      development of clinical phenomena.

PMID- 15870615
TI  - Decision-making capacity of inpatients with schizophrenia in Hong Kong.
AB  - This is a prospective study examining decision-making abilities in Chinese
      schizophrenia patients in Hong Kong. We interviewed patients before their
      discharge from hospital after a psychotic relapse, examining their decision
      regarding whether or not they would take maintenance neuroleptic treatment.
      Decision-making abilities were assessed by the MacArthur Competence Assessment
      Tool-Treatment, a semistructured questionnaire. We examined their relationships
      with demographic, clinical, and cognitive variables, measured by standardized
      instruments. Eighty-one participants were seen. Weaknesses were noted in a range
      of relevant decision-making abilities. Positive and negative schizophrenic
      symptoms, specifically lack of judgment and insight, difficulty in abstract
      thinking, unusual thought content, and conceptual disorganization, were found to
      be correlated with performance in decision-making abilities, as were cognitive
      deficits. Verbal working memory was a moderate predictor of the ability to
      understand treatment information. Decision-making impairments and negative
      treatment attitude were related to the decision not to adhere to medication.

PMID- 15870616
TI  - When euthymia is just not good enough: the neuropsychology of bipolar disorder.
AB  - Bipolar disorder (BD) is a debilitating psychiatric illness that is uniquely
      characterized by switching between psychopathologically contrasting phases of
      mania and depression, often with intervening periods of euthymia. However, these
      periods of apparent clinical recovery (euthymia) are marked by subtle social,
      occupational, and cognitive impairments, profiled by recent neuropsychological
      investigations. Determining the cognitive changes across these three phases may
      help differentiate the disruptions that are mood state-dependent from those
      associated with underlying pathology. This article therefore critically reviews
      the reported neuropsychological impairments in BD and the methodological
      limitations facing such research. Integration of the available evidence,
      principally from the field of neuropsychology, when synthesized, implicates the
      prefrontal cortex in the etiopathogenesis of BD and posits cortical-subcortical
      limbic disruption in recovered euthymic patients that manifests as cognitive
      dysfunction.

PMID- 15870617
TI  - Reduced awareness of others' emotions in unipolar depressed patients.
AB  - The present study was conducted to examine depressed patients' awareness of their
      own and other persons' emotions in the course of an inpatient psychotherapeutic
      treatment program. To this aim, the Levels of Emotional Awareness Scale (LEAS)
      was administered twice, approximately 7 weeks apart, to 22 patients with a
      unipolar depression and 22 normal controls. From test 1 to test 2, severity of
      patients' depressive symptoms as measured by the Beck Depression Inventory
      improved significantly. Depressed patients did not differ from normal individuals
      on the LEAS-self score, but at time 1, they exhibited lower LEAS-other scores
      than normal controls. In the whole sample, LEAS-other scores increased
      significantly from time 1 to time 2. Acutely depressed patients seem not to be
      impaired in the complexity of their own emotional experience, but they exhibit a
      reduction in the ability to empathize with other persons.

PMID- 15870618
TI  - Maternal depression and the intergenerational transmission of religion.
AB  - This study tests the hypothesis that maternal depression (major depressive
      disorder; MDD) decreases rates of the intergenerational transmission of
      religiosity from mother to offspring and attenuates the beneficial qualities of
      religiosity in offspring. Depression was assessed using semistructured clinical
      interviews; religiosity was assessed based upon the personal importance of
      religion, frequency of attendance at religious services, and religious
      denomination. Results suggest that (1) maternal depression attenuates the
      intergenerational transmission of religion; (2) in the presence of maternal
      depression, offspring were more likely to have MDD at 10-year follow-up when
      mother-offspring were concordant on religious importance; and (3) in the absence
      of maternal depression, offspring were less likely to have MDD at 10-year follow
      up when mother-offspring were concordant on attendance. Thus, in the presence of
      maternal depression, transmission of religious attendance is no longer associated
      with decreased likelihood of offspring MDD, whereas transmission of religious
      importance is associated with increased likelihood of offspring depression.

PMID- 15870619
TI  - Inverse correlations between symptom scores and spiritual well-being among
      African American patients with first-episode schizophrenia spectrum disorders.
AB  - Spirituality, religiosity, and spiritual/religious well-being are relatively
      understudied in the context of severe mental illnesses. Nonetheless, individuals
      dealing with such disorders, including schizophrenia, often make use of
      spirituality and religious affiliation as coping resources. In this preliminary
      study, we examined correlations between psychopathology severity and spiritual
      well-being among first-episode schizophrenia-spectrum disorder patients. The
      sample consisted of 18 African American patients hospitalized on an inpatient
      psychiatric unit in a large, urban, public hospital. After confirmation of
      diagnosis with the Structured Clinical Interview for DSM-IV Axis I Disorders,
      symptom severity was rated with the Positive and Negative Syndrome Scale, and
      self-reported spiritual well-being was evaluated with the Spiritual Well-Being
      Scale. Spearman correlations revealed that negative symptom scores were inversely
      correlated with religious well-being scores (rho = -.614; p = 0.007), and that
      general psychopathology symptom scores were inversely correlated with existential
      well-being scores (rho = -.539; p = 0.021). These preliminary findings indicate
      that negative symptoms and general psychopathology symptoms may have a
      detrimental effect on religious and existential well-being in patients with a
      first episode of a schizophrenia-spectrum disorder, or that religious and
      existential well-being may have an effect on symptomatology.

PMID- 15870620
TI  - Altered subjective time of events in schizophrenia.
AB  - Time perception has long been known to be impaired in schizophrenia. Moreover,
      recent neuropsychological theories have postulated abnormalities of cognitive
      motor control in schizophrenia. However, the intersection of these two topics has
      rarely been studied, and it is unclear what role subjects' own actions may play
      in the construction of subjective time representation. The present experiment
      compared the performance of 19 patients with schizophrenia and 24 normal controls
      in a timing judgment task. The results show that patients bind two consecutive
      movements more strongly than controls. This anomaly could play a role in the
      subjective pathological experiences of patients.

PMID- 15870621
TI  - Allergic rhinitis and pharmacological management in elite athletes.
AB  - INTRODUCTION: Only a few studies have examined the occurrence of atopy and
      clinically apparent allergic disease and their pharmacological management in
      elite athletes. The aim of the study was to assess the frequency of allergic
      rhinitis and the use of antiallergic medication within the subgroups of elite
      athletes as compared with a representative sample of young adults of the same
      age. METHODS: A cross-sectional survey was carried out in 2002. All the athletes
      (N = 494) financially supported by the National Olympic Committee comprised the
      study group. Of them, 446 (90.3%) filled in a structured questionnaire concerning
      asthma and allergies, the use of medication, characteristics of sport activities,
      and smoking habits. A representative sample of Finnish young adults (N = 1504)
      served as controls. RESULTS: The endurance athletes reported physician-diagnosed
      allergic rhinitis more often (36.1%) than other athletes (23.4%) or control
      subjects (20.2%). The use of antiallergic medication was reported by 33.3, 15.7,
      and 15.6% of those, respectively. Among both athletes and controls, females
      reported the use of antiallergic medication more often than males. Only half of
      those athletes reporting allergic rhinitis had used antiallergic medication
      during the past year. After adjusting for age and sex, OR (95% CI) for allergic
      rhinitis and the use of antiallergic medication were 2.24 (1.48-3.39) and 2.79
      (1.82-4.28), respectively, in endurance athletes as compared with the controls.
      CONCLUSIONS: Endurance athletes have physician-diagnosed allergic rhinitis, and
      they use antiallergic medication more often than athletes in other events or
      control subjects. Only half of those athletes reporting allergic rhinitis take
      antiallergic medication. More attention needs to be paid to the optimal
      management of allergic rhinitis, especially in highly trained endurance athletes.

PMID- 15870622
TI  - Effects of indomethacin and celecoxib on renal function in athletes.
AB  - INTRODUCTION: Strenuous exercise induces a marked reduction in renal
      hemodynamics. Prostaglandins (PG) play an important role in maintaining renal
      integrity in the face of hemodynamic changes. Inhibition of cyclooxygenase (COX)
      and thus PG formation can further compromise renal perfusion. The role of
      selective COX-2 inhibition on renal hemodynamics during exercise has not been
      investigated. METHODS: Twelve healthy males (22-47 yr) took part in a randomized
      placebo controlled study investigating the effects of nonselective COX inhibition
      (indomethacin) and COX-2 selective inhibition (celecoxib) on renal hemodynamics
      during exercise. Renal blood flow (RBF), glomerular filtration rate (GFR), and
      free water clearance were measured using standard clearance techniques. Each
      experimental session was performed at least a week apart. The medications were
      taken for 36 h before study with the last dose at 0700 h on the day of study.
      Following baseline studies, each participant exercised for 30 min at 80% of their
      maximal aerobic power. Renal function was monitored for 2 h post-recovery.
      RESULTS: RBF and GFR fell by 40% after exercise with no significant difference
      between placebo, indomethacin, or celecoxib. Indomethacin (-2.43 +/- 0.95 mL x
      min(-1), P < 0.007) and celecoxib (-3.88 +/- 0.94 mL x min(-1), P < 0.0001)
      significantly reduced free water clearance compared with placebo during recovery.
      CONCLUSION: This study has confirmed that selective and nonselective COX
      inhibition can induce significant inhibition of free water clearance, indicating
      that these acute changes are regulated predominantly via COX-2. Acute cerebral
      edema with hyponatremia has been reported after major endurance sporting events.
      Identifiable risk factors include excessive hydration and use of NSAID. Impaired
      free water clearance during exercise potentiated by COX inhibition provides a
      pathophysiological explanation for these observations.

PMID- 15870623
TI  - Disability type influences heart rate response during power wheelchair sport.
AB  - PURPOSE: The purpose of this study was to determine the influence of disability
      type on exercise response during power wheelchair competition. The secondary
      purpose was to determine the extent to which heart rate responses during
      competition meet cardiorespiratory fitness training intensities for the general
      population. METHODS: Forty-eight athletes who had cerebral palsy (CP, N = 31),
      spinal cord injury (SCI, N = 10), or muscular dystrophy (MD, N = 7), and were
      competing in the 2003 Power Soccer National Tournament, volunteered to
      participate. Heart rate was recorded every 5 s throughout pre-game and game
      conditions by Polar S610 monitors. Average heart rate (HR) values were determined
      for GAME and RESPONSE (change score between GAME HR and pre-game HR). The Kruskal
      Wallis nonparametric test was used to determine whether a significant difference
      among group medians existed on the dependent measure, RESPONSE (P < 0.05).
      RESULTS: A significant difference on RESPONSE (P < 0.05) existed among athletes
      with CP (29 bpm), SCI (17 bpm), and MD (26 bpm). The median RESPONSE for athletes
      with CP was 12 bpm higher than athletes with SCI, and this difference was
      significant (P < 0.01). Further, 22 athletes with CP (71%), 5 athletes with MD
      (71%), and 1 athlete with SCI (10%) exceeded 55% of estimated HR(max) for at
      least 30 min during competition. CONCLUSION: Disability type influences the heart
      rate response to power wheelchair sport, and may affect the ability to sustain
      training intensities associated with fitness improvement.

PMID- 15870624
TI  - A Colorado statewide survey of walking and its relation to excessive weight.
AB  - INTRODUCTION: There is an urgent need to increase the physical activity in the
      population. Small-scale success has been achieved in programs like Colorado on
      the Move (COM), an obesity prevention program using electronic pedometers.
      METHODS: To provide baseline information for COM, this first-ever statewide
      survey of walking was conducted with 1098 individuals. The weighted mean BMI was
      25.3 +/- 0.18 kg x m(-2), and mean age was 44 +/- 0.42 yr of age. Subjects
      participated in a short telephone interview and then were sent a pedometer to
      wear for four consecutive days. A total of 742 of the 1098 subjects completed the
      pedometer phase. RESULTS: The average adult in Colorado reported taking 6804
      steps per day. About 33% reported taking fewer than 5000 steps per day, and only
      16% reported taking 10,000 or more steps per day. Steps per day increased with
      other self-reported measures of physical activity (P = 0.0001) and decreased with
      self-reported inactivity (P = 0.0001). Significant determinants of steps per day
      included increasing age (negative, P = 0.001), marital status (positive for
      single status, P = 0.05), income (positive for incomes of dollar 25,000 to dollar
      99,000, P = 0.003), and increasing BMI (negative for BMI > or = 30 kg x m(-2), P
      = 0.000). Obese individuals (BMI > or = 30 kg x m(-2)) walked about 2000 fewer
      steps per day than normal-weight individuals. These results provide the first
      population data on current walking levels, on how this relates to self-reported
      physical activity, and on determinants of walking. Results also provide a
      baseline level of walking for future evaluation of COM. CONCLUSION: Increasing
      steps per day appears to be a good target to use in interventions to increase
      physical activity. Even in Colorado, one of the leanest states, very low levels
      of physical activity are seen in much of the population.

PMID- 15870625
TI  - Increased IGF mRNA in human skeletal muscle after creatine supplementation.
AB  - PURPOSE: We hypothesized that creatine supplementation would facilitate muscle
      anabolism by increasing the expression of growth factors and the phosphorylation
      of anabolic signaling molecules; we therefore tested the responses of mRNA for
      IGF-I and IGF-II and the phosphorylation state of components of anabolic
      signaling pathways p70(s6k) and 4E-BP1 to a bout of high-intensity resistance
      exercise after 5 d of creatine supplementation. METHODS: In a double-blind cross
      over design, muscle biopsies were taken from the m. vastus lateralis at rest and
      3 and 24 h postexercise in subjects who had taken creatine or placebo for 5 d (21
      g x d(-1)). For the first 3 h postexercise, the subjects were fed with a drink
      containing maltodextrin (0.3 g x kg(-1) body weight x h(-1)) and protein (0.08 g
      x kg(-1) body weight x h(-1)). RESULTS: After creatine supplementation, resting
      muscle expressed more mRNA for IGF-I (+30%, P < 0.05) and IGF-II (+40%, P =
      0.054). Exercise caused an increase by 3 h postexercise in IGF-I (+24%, P < 0.05)
      and IGF-II (+48%, P < 0.05) and by 24 h postexercise in IGF-I (+29%, P < 0.05),
      but this effect was not potentiated by creatine supplementation. The
      phosphorylation states of p70(s6k) and 4E-BP1 were not affected by creatine at
      rest; phosphorylation of both increased (150-400%, P < 0.05) to similar levels
      under placebo and creatine conditions at 3 h postexercise plus feeding. However,
      the phosphorylation state of 4E-BP1 was higher in the creatine versus placebo
      condition at 24 h postexercise. CONCLUSION: The increase in lean body mass often
      reported after creatine supplementation could be mediated by signaling pathway(s)
      involving IGF and 4E-BP1.

PMID- 15870626
TI  - Exercise-induced muscle damage, plasma cytokines, and markers of neutrophil
      activation.
AB  - INTRODUCTION: Unaccustomed eccentric exercise often results in muscle damage and
      neutrophil activation. We examined changes in plasma cytokines stress hormones,
      creatine kinase activity and myoglobin concentration, neutrophil surface receptor
      expression, degranulation, and the capacity of neutrophils to generate reactive
      oxygen species in response to in vitro stimulation after downhill running.
      METHODS: Ten well-trained male runners ran downhill on a treadmill at a gradient
      of -10% for 45 min at 60% VO2max. Blood was sampled immediately before (PRE) and
      after (POST), 1 h (1 h POST), and 24 h (24 h POST) after exercise. RESULTS: At
      POST, there were significant increases (P < 0.01) in neutrophil count (32%),
      plasma interleukin (IL)-6 concentration (460%), myoglobin (Mb) concentration
      (1100%), and creatine kinase (CK) activity (40%). At 1 h POST, there were further
      increases above preexercise values for neutrophil count (85%), plasma Mb levels
      (1800%), and CK activity (56%), and plasma IL-6 concentration remained above
      preexercise values (410%) (P < 0.01). At 24 h POST, neutrophil counts and plasma
      IL-6 levels had returned to baseline, whereas plasma Mb concentration (100%) and
      CK activity (420%) were elevated above preexercise values (P < 0.01). There were
      no significant changes in neutrophil receptor expression, degranulation and
      respiratory burst activity, and plasma IL-8 and granulocyte-colony stimulating
      factor concentrations at any time after exercise. Neutrophil count correlated
      with plasma Mb concentration at POST (r = 0.64, P < 0.05), and with plasma CK
      activity at POST (r = 0.83, P < 0.01) and 1 h POST (r = 0.78, P < 0.01).
      CONCLUSION: Neutrophil activation remains unchanged after downhill running in
      well-trained runners, despite increases in plasma markers of muscle damage.

PMID- 15870627
TI  - Partial protection against muscle damage by eccentric actions at short muscle
      lengths.
AB  - PURPOSE: This study investigated the hypothesis that maximal eccentric actions at
      a short muscle length would fail to confer a protective effect against muscle
      damage induced by maximal eccentric exercise at a long muscle length. METHODS:
      Eleven males performed 24 maximal eccentric actions of the nondominant elbow
      flexors over a short extension range from an elbow joint angle of 0.87-1.74 rad
      (S-ECC) followed 4 wk later by eccentric actions at a long range of 2.27-3.14 rad
      (L-ECC). A second group of 11 males performed L-ECC on two occasions using the
      nondominant arm separated by 4 wk. Changes in maximal isometric strength, range
      of motion, upper arm circumference, muscle soreness, plasma creatine kinase and
      aspartate aminotransferase activities, and B-mode ultrasound images were compared
      between bouts and between groups by two-way repeated measures ANOVA. RESULTS: All
      measures changed significantly (P < 0.01) after the first bout; however, the
      effects were significantly (P < 0.01) smaller after S-ECC compared with L-ECC.
      The second bout resulted in significantly (P < 0.01) reduced changes in all
      measures compared with the first bout in the subjects who performed L-ECC on both
      occasions. The subjects who performed S-ECC in the first bout displayed
      significantly smaller changes after L-ECC than those seen after L-ECC alone, with
      the degree of attenuation being around 50-70%. CONCLUSION: Contrary to the
      hypothesis, S-ECC provided partial but effective protection against L-ECC. This
      result suggests adaptations associated with the repeated bout effect were also
      produced after S-ECC, but the degree of adaptations was not as strong as that by
      L-ECC. Eccentric exercise at a short extension range can be used as a strategy to
      present severe muscle damage.

PMID- 15870628
TI  - Respiratory muscle strength may explain hypoxia-induced decrease in vital
      capacity.
AB  - PURPOSE: High altitude exposure has consistently been reported to decrease forced
      vital capacity (FVC), but the mechanisms accounting for this observation remain
      incompletely understood. We investigated the possible contribution of a hypoxia
      related decrease in respiratory muscle strength. METHODS: Maximal inspiratory and
      expiratory pressures (MIP and MEP), sniff nasal inspiratory pressure (SNIP), FVC,
      peak expiratory flow rate (PEF), and forced expiratory volume in 1 s (FEV1) were
      measured in 15 healthy subjects before and after 1, 6, and 12 h of exposure to an
      equivalent altitude of 4267 m in a hypobaric chamber. RESULTS: Hypoxia was
      associated with a progressive decrease in FVC (5.59 +/- 0.24 to 5.24 +/- 0.26 L,
      mean +/- SEM, P < 0.001), MIP (130 +/- 10 to 114 +/- 8 cm H2O, P < 0.01), MEP
      (201 +/- 12 to 171 +/- 11 cm H2O, P < 0.001), and SNIP (125 +/- 7 to 98 +/- 7 cm
      H2O, P < 0.001). MIP, MEP, and SNIP were strongly correlated to FVC (r ranging
      from 0.77 to 0.92). FEV1 didn't change, and PEF increased less than predicted by
      the reduction in air density (11-20% of sea-level value compared with 32%
      predicted). CONCLUSION: We conclude that a decrease in respiratory muscle
      strength may contribute to the decrease in FVC observed at high altitude.

PMID- 15870629
TI  - Effects of induced metabolic alkalosis on prolonged intermittent-sprint
      performance.
AB  - PURPOSE: Previous studies have shown that induced metabolic alkalosis, via sodium
      bicarbonate (NaHCO3) ingestion, can improve short-term, repeated-sprint ability.
      The purpose of this study was to assess the effects of NaHCO3 ingestion on a
      prolonged, intermittent-sprint test (IST). METHODS: Seven female team-sport
      athletes (mean +/- SD: age = 19 +/- 1 yr, VO2peak = 45.3 +/- 3.1 mL x kg(-1) x
      min(-1)) volunteered for the study, which had received ethics clearance. The
      athletes ingested two doses of either 0.2 g x kg(-1) of NaHCO3 or 0.138 g x kg(
      1) of NaCl (placebo), in a double-blind, random, counterbalanced order, 90 and 20
      min before performing the IST on a cycle ergometer (two 36-min "halves" of
      repeated approximately 2-min blocks: all-out 4-s sprint, 100 s of active recovery
      at 35% VO2peak, and 20 s of rest). Capillary blood samples were drawn from the
      ear lobe before ingestion, and before, during, and after each half of the IST.
      VO2 was also recorded at regular intervals throughout the IST. RESULTS: Resting
      plasma bicarbonate concentration ([HCO3-]) averaged 22.6 +/- 0.9 mmol x L(-1),
      and at 90 min post-ingestion was 21.4 +/- 1.5 and 28.9 +/- 2.8 mmol x L-1 for the
      placebo and NaHCO3 conditions, respectively (P < 0.05). Plasma [HCO3-] during the
      NaHCO3 condition remained significantly higher throughout the IST compared with
      both placebo and pre-ingestion. There was a trend toward improved total work in
      the second (P = 0.08), but not first, half of the IST after the ingestion of
      NaHCO3. Furthermore, subjects completed significantly more work in 7 of 18 second
      half, 4-s sprints after NaHCO3 ingestion. CONCLUSIONS: The results of this study
      suggest that NaHCO3 ingestion can improve intermittent-sprint performance and may
      be a useful supplement for team-sport athletes.

PMID- 15870630
TI  - Modulation of immune response by the acute and chronic exposure to high altitude.
AB  - PURPOSE: The chronic exposure at high altitude (HA) represents an ideal model for
      evaluating the in vivo effects of hypobaric hypoxia. Taking advantage of the EV
      K2-CNR Pyramid, this study was designed to evaluate whether acute and chronic
      hypoxia differently modulates the in vivo immune responses. METHODS: The study
      includes 13 healthy female moderately active volunteers participating to the
      Italian HA project EV-K2-CNR. Peripheral blood lymphocytes, collected at sea
      level and at HA in the Pyramid Laboratory of CNR, Nepal (5050 m), were
      immunologically characterized by flow cytometry and a series of molecular and
      functional analyses. RESULTS: Flow cytometric analyses showed that: a) CD3+ T
      lymphocytes significantly decreased during both acute and chronic exposure to HA,
      b) T-cell fall was totally due to CD4+ T-cell reduction, c) B lymphocytes were
      not influenced by the exposure to HA, and d) natural killer (NK) cells
      significantly increased during acute and chronic exposure. The evaluation of the
      Th1/Th2 pattern demonstrated a significant decrease of the expression of the Th1
      cytokine interferon-gamma (IFN-gamma) by circulating T cells during acute and
      chronic exposure to HA. The expression by T cells of CXCR3, a chemokine receptor
      typically expressed by Th1/Tc1 cells, paralleled the decrease of IFN-gamma. On
      the contrary, the expression of IL-4 was not conditioned by the exposure to HA.
      Finally, functional studies showed a significant reduction of the proliferative
      activity in response to mitogen (PHA) both in acute and chronic HA exposure.
      Despite the increased number of NK cells, NK cytotoxic activity was not
      influenced by the HA exposure. CONCLUSIONS: Our results indicate that the in vivo
      exposure to HA leads to an impairment of the homeostatic regulation of Th1/Th2
      immune balance that potentially could favor long-term immunological alterations
      and increase the risk of infections.

PMID- 15870631
TI  - Effect of prior exercise above and below critical power on exercise to
      exhaustion.
AB  - PURPOSE: The aim of the present study was to ascertain whether the intensity of
      prior exercise altered the time to exhaustion at critical power (CP). METHODS:
      Eleven participants volunteered to take part in the study (mean +/- SD: VO2max
      4.1 +/- 0.5 L x min(-1); age 30.1 +/- 7.2 yr; body mass 74.6 +/- 9.1 kg) and
      completed three trials to exhaustion at their CP under differing prior exercise
      conditions: 1) a control trial (CON); 2) a trial preceded by three 60-s efforts
      at 110% CP (severe); and 3) a trial preceded by three 73-s efforts at 90% CP
      (heavy). All trials followed a 5-min baseline at 50 W. RESULTS: Time to
      exhaustion was significantly lengthened after prior heavy exercise (1071 +/- 18
      s) when compared with CON (973 +/- 16 s, F = 9.53, P = 0.006). However, there was
      no effect on TTE after prior severe exercise (967 +/- 16 s). Oxygen deficit was
      significantly reduced from that in CON (3.8 +/- 0.2 L) after prior heavy (3.2 +/-
      0.3 L) and prior severe exercise (3.1 +/- 0.3 L, F = 10.95, P = 0.001).
      Concurrently, there was a significant reduction in the magnitude of the VO2 slow
      component (SC) in the trials with prior exercise (197 +/- 34 and 126 +/- 19 mL x
      min(-1) after heavy and severe exercise, respectively) when compared with CON
      (223 +/- 31 mL x min(-1), F = 9.62, P = 0.006). CONCLUSION: Prior heavy exercise
      does appear to improve the time to exhaustion at CP by approximately 10% and is
      associated with a reduction in the VO2 SC. However, the reduction in the SC, with
      no change in performance after prior severe exercise, suggests that a reduced SC
      may not necessarily lead to improved TTE.

PMID- 15870632
TI  - O2 arterial desaturation in endurance athletes increases muscle deoxygenation.
AB  - PURPOSE: The aim of this study was to compare the muscle deoxygenation measured
      by near infrared spectroscopy in endurance athletes who presented or not with
      exercise-induced hypoxemia (EIH) during a maximal incremental test in normoxic
      conditions. METHODS: Nineteen male endurance sportsmen performed an incremental
      test on a cycle ergometer to determine maximal oxygen consumption (VO2max) and
      the corresponding power output (P(max)). Arterial O2 saturation (SaO2) was
      measured noninvasively with a pulse oxymeter at the earlobe to detect EIH, which
      was defined as a drop in SaO2 > 4% between rest and the end of the exercise.
      Muscle deoxygenation of the right vastus lateralis was monitored by near infrared
      spectroscopy and was expressed in percentage according to the ischemia-hyperemia
      scale. RESULTS: Ten athletes exhibited arterial hypoxemia (EIH group) and the
      nine others were nonhypoxemic (NEIH group). Training volume, competition level,
      VO2max, Pmax, and lactate concentration were similar in the two groups.
      Nevertheless, muscle deoxygenation at the end of the exercise was significantly
      greater in the EIH group (P < 0.05). CONCLUSION: Greater muscle deoxygenation at
      maximal exercise in hypoxemic athletes seems to be due, at least in part, to
      reduced oxygen delivery--that is, exercise-induced hypoxemia--to working muscle
      added to the metabolic demand. In addition, our finding is also consistent with
      the hypothesis of greater muscle oxygen extraction in order to counteract reduced
      O2 availability.

PMID- 15870633
TI  - Sex differences in voluntary fluid intake by older adults during exercise.
AB  - PURPOSE: This study compared the voluntary fluid intake behavior of older men and
      women (54-70 yr) when provided cold, palatable beverages and ample opportunity to
      drink between repeated bouts of exercise in the heat. METHODS: Thirteen men and
      14 women performed four bouts of 15-min cycling at 65% VO2peak followed by 15 min
      of rest at 30 degrees C and 50% relative humidity. In separate trials, subjects
      drank either a carbohydrate-electrolyte solution (CES) or water ad libitum during
      the rest periods and were unaware that their fluid intake was being measured.
      RESULTS: Fluid intake behavior was repeatable (intraclass correlation coefficient
      = 0.75), and subjects drank enough of either beverage to match sweating rates and
      maintain their body mass (BM). Fluid intake per kilogram of BM was greater with
      CES (18.7 +/- 2.2 vs 15.1 +/- 2.1 mL x kg(-1); P < 0.05), and plasma volume (PV)
      was better maintained during the CES trials (-1.3 +/- 1.1 vs -4.2 +/- 1.1% during
      the second half of the session). Women drank significantly more water than the
      men on a per kilogram basis (17.2 +/- 2.9 vs 12.8 +/- 1.7 mL x kg(-1) BM), and
      one woman (BM = 45.7 kg) became hyponatremic (S(NA) = 126 mmol x L(-1)) with
      symptoms during the water trial. CONCLUSION: Older adults drank enough to
      maintain fluid balance when palatable fluid was readily available; however, CES
      promoted greater voluntary fluid intake and restored PV losses faster than water.
      In addition, older women drank more water than men during interval exercise in
      the heat, which may put smaller women at an increased risk for developing
      hyponatremia.

PMID- 15870634
TI  - Consequences of ankle joint fixation on FES cycling power output: a simulation
      study.
AB  - INTRODUCTION: During fixed-ankle FES cycling in paraplegics, in which the leg
      position is completely determined by the crank angle, mechanical power output is
      low. This low power output limits the cardiovascular load that could be realized
      during FES ergometer cycling, and limits possibilities for FES cycling as a means
      of locomotion. Stimulation of ankle musculature in a released-ankle setup might
      increase power output. However, releasing the ankle joint introduces a degree of
      freedom in the leg that has to be controlled, which imposes constraints on the
      stimulation pattern. METHODS: In this study, a forward dynamics
      modeling/simulation approach was used to assess the potential effect of releasing
      the ankle on the maximal mechanical power output. RESULTS: For the released-ankle
      setup, the optimal stimulation pattern was found to be less tightly related to
      muscle shortening/lengthening than for the fixed-ankle setup, which indicates the
      importance of the constraints introduced by releasing the ankle. As a result, the
      maximal power output for 45-RPM cycling in the released-ankle setup was found to
      be about 10% lower than with a fixed ankle, despite the additional muscle mass
      available for stimulation. Power output for the released-ankle setup can be
      improved by tuning the point of contact between the foot and pedal to the
      relative strength of the ankle plantar flexors. For the model used, power output
      was 14% higher than for the fixed-ankle setup when this point of contact was
      moved posteriorly by 0.075 m. CONCLUSION: Releasing the ankle joint and
      stimulating the triceps surae and tibialis anterior is expected to result in a
      modest increase in power output at best.

PMID- 15870635
TI  - Biomechanical analysis of double poling in elite cross-country skiers.
AB  - PURPOSE: To further the understanding of double poling (DP) through biomechanical
      analysis of upper and lower body movements during DP in cross-country (XC) skiing
      at racing speed. METHODS: Eleven elite XC skiers performed DP at 85% of their
      maximal DP velocity (V85%) during roller skiing at 1 degrees inclination on a
      treadmill. Pole and plantar ground reaction forces, joint angles (elbow, hip,
      knee, and ankle), cycle characteristics, and electromyography (EMG) of upper and
      lower body muscles were analyzed. RESULTS: 1) Pole force pattern with initial
      impact force peak and the following active force peak (PPF) correlated to V85%,
      (r = 0.66, P < 0.05); 2) active flexion-extension pattern in elbow, hip, knee,
      and ankle joints with angle minima occurring around PPF, correlated to hip angle
      at pole plant (r = -0.89, P < 0.01), minimum elbow angle (r = -0.71), and
      relative poling time (r = -0.72, P < 0.05); 3) two different DP strategies (A and
      B), where strategy A (best skiers) was characterized by higher angular elbow- and
      hip-flexion velocities, smaller minimum elbow (P < 0.01) and hip angles (P <
      0.05), and higher PPF (P < 0.05); 4) EMG activity in trunk and hip flexors,
      shoulder, and elbow extensors, and several lower body muscles followed a specific
      sequential pattern with changing activation levels; and 5) EMG activity in lower
      body muscles showed DP requires more than upper body work. CONCLUSIONS: DP was
      found to be a complex movement involving both the upper and lower body showing
      different strategies concerning several biomechanical aspects. Future research
      should further investigate the relationship between biomechanical and
      physiological variables and elaborate training models to improve DP performance.

PMID- 15870636
TI  - Validation of the Children's OMNI-Resistance Exercise Scale of perceived
      exertion.
AB  - PURPOSE: This investigation examined concurrent validity of the Children's OMNI
      Resistance Exercise Scale (OMNI-RES) of perceived exertion for 10- to 14-yr-old
      females (N = 25) and males (N = 25) performing unilateral biceps curl (BC) and
      knee extension (KE) isotonic exercises. METHODS: The criterion variable was total
      weight lifted (Wt(tot)), determined separately for females and males during BC
      and KE. Subjects performed three separate sets of 6, 10, and 14 repetitions for
      BC and KE at 50% 1-RM. Ratings of perceived exertion for the active muscles (RPE
      AM) and overall body (RPE-Overall) were measured during the final repetition.
      RESULTS: For both female and male groups across the three sets: (a) RPE-AM ranged
      from 2.9 to 8.3 for BC and 4.5 to 9.6 for KE, and (b) RPE-O ranged from 1.9 to
      7.0 for BC and 3.6 to 7.7 for KE. Positive linear regression coefficients ranged
      from r = 0.72 to 0.88 (P < 0.01) between Wt(tot) and RPE-AM and RPE-Overall for
      BC and KE in both gender groupings. RPE did not differ between females and males
      at any measurement point within each set for BC and KE. RPE-AM was greater (P <
      0.01) than RPE-Overall in the three sets of BC and KE. CONCLUSION: Findings
      provided concurrent validation of the Children's OMNI-RES to measure RPE for the
      active muscle and overall body in 10- to 14-yr-old females and males performing
      upper and lower body resistance exercise.

PMID- 15870637
TI  - Use of self-assessed fitness and exercise parameters to predict objective
      fitness.
AB  - PURPOSE: The purpose of this prospective study was to examine the effectiveness
      of self-assessed fitness and exercise in predicting objectively measured physical
      fitness. METHODS: Study subjects included 1583 men who entered Marine Corps
      training in San Diego, CA, between September and November 2002 and completed a
      questionnaire and an objective fitness test. The questionnaire included
      demographic and self-assessed fitness/exercise items, and was administered
      immediately upon entry into the training program. The objective fitness measure
      was obtained using a standardized test after approximately 1 month of training.
      RESULTS: Multivariate modeling found that several measures of self-assessed
      fitness and exercise (estimated number of pull-ups; good, very good, or excellent
      self-assessed fitness; sweating quite a lot or most or all of the time during
      physical activity; and competitive experience) were all associated with the
      objective fitness score. These results remained statistically significant after
      controlling for age, race, and body mass index (model adjusted R2 = 0.469, P <
      0.01). CONCLUSION: In this analysis, self-assessed fitness and exercise
      parameters that can be easily ascertained with a short questionnaire predicted
      objective fitness scores approximately 1 month later. This information could be
      used by recruiters to make recommendations for pre-enlistment conditioning.

PMID- 15870639
TI  - Effects of prior warm-up regime on severe-intensity cycling performance.
AB  - PURPOSE: The purpose of the present study was to determine the effect of three
      different warm-up regimes on cycling work output during a 7-min performance
      trial. METHODS: After habituation to the experimental methods, 12 well-trained
      cyclists completed a series of 7-min performance trials, involving 2 min of
      constant-work rate exercise at approximately 90% VO2max and a further 5 min
      during which subjects attempted to maximize power output. This trial was
      performed without prior intervention and 10 min after bouts of moderate, heavy,
      or sprint exercise in a random order. Pulmonary gas exchange was measured breath
      by breath during all performance trials. RESULTS: At the onset of the performance
      trial, baseline blood [lactate] was significantly elevated after heavy and sprint
      but not moderate exercise (mean +/- SD: control, 1.0 +/- 0.3 mM; moderate, 1.0 +/
      0.2 mM; heavy, 3.0 +/- 1.1 mM; sprint, 5.9 +/- 1.5 mM). All three interventions
      significantly increased the amplitude of the primary VO2 response (control, 2.59
      +/- 0.28 L x min(-1); moderate, 2.69 +/- 0.27 L x min(-1); heavy, 2.78 +/- 0.26 L
      x min(-1); sprint, 2.78 +/- 0.30 L x min(-1)). Mean power output was
      significantly increased by prior moderate and heavy exercise but not
      significantly reduced after sprint exercise (control, 330 +/- 42 W; moderate, 338
      +/- 39 W; heavy, 339 +/- 42 W; sprint, 324 +/- 45 W). CONCLUSIONS: These data
      indicate that priming exercise performed in the moderate- and heavy-intensity
      domains can improve severe-intensity cycling performance by ~2-3%, the latter
      condition doing so despite a mild lactacidosis being present at exercise onset.

PMID- 15870638
TI  - Pregnancy-related changes in physical activity, fitness, and strength.
AB  - PURPOSE: The objective was to examine the pregnancy-related changes in physical
      activity, fitness, and strength in women of varying body mass indices (BMI).
      METHODS: Women (N = 17 low BMI, N = 34 normal BMI, and N = 12 high BMI, mean age
      +/- SD = 30.7 +/- 4.1 yr) were studied before pregnancy (0 wk) and postpartum (6
      and 27 wk) for body composition and for physical activity, fitness, and strength.
      Physical activity was assessed by questionnaire, fitness by a maximal oxygen
      consumption (VO2) test on a cycle ergometer, and strength by the one-repetition
      maximum test. Data were analyzed by repeated measures ANOVA testing for time and
      BMI group. RESULTS: Total physical activity differed qualitatively, but not
      quantitatively, with time. Significant time effects were observed for maximal
      workload, heart rate, respiration rate, ventilation, VO2, respiratory exchange
      ratio, and strength. VO2max, adjusted for weight, dropped by approximately 385 mL
      x min(-1) from 0 to 6 wk postpartum (P < 0.0001) and by approximately 234 mL x
      min(-1) from 0 to 27 wk postpartum (P < 0.01). The high-BMI group had a lower
      VO2max (adjusted for weight or fat-free mass) than the normal-BMI group (P <
      0.05). Strength decreased for the leg press by 24% (P < 0.02) and for the
      latissimus pull down by 8% (P < 0.01) from 0 to 6 wk postpartum, and then
      increased by 44 and 12%, respectively (both P < 0.05), by 27 wk postpartum.
      CONCLUSION: Relative to prepregnancy performance, fitness and strength declined
      in the early postpartum period but improved by 27 wk postpartum.

PMID- 15870640
TI  - Metabolic recovery in professional road cyclists: a 31P-MRS study.
AB  - PURPOSE: Aerobic training of professional road cyclists is linked to tremendous
      aerobic capacities that have never been clearly related to what occur in skeletal
      muscles submitted to a specific exercise. The aim of the present study was to
      examine specifically metabolic recovery after an incremental cycling exercise
      performed until exhaustion in professional road cyclists as compared with
      moderately trained subjects and so using 31P- MRS. METHODS: Subjects performed a
      progressive cycling exercise on a cycloergometer until exhaustion, then they were
      positioned back in the magnet (delay lower than 45 s) for recovery scanning. 31P
      spectra of thigh muscles were time averaged in 2-s blocks at rest and for 15 min
      throughout the recovery period. RESULTS: For a significantly more intense
      exercise (477 +/- 28 vs 334 +/- 24 W in controls; P < 0.001), professional road
      cyclists displayed similar end-of-exercise extrapolated pH values (6.43 +/- 0.16
      vs. 6.34 +/- 0.05 in controls) and a significantly higher PCr concentration (20.1
      +/- 0.8 vs. 13.3 +/- 0.5 mM in controls, P < 0.001). The pH recovery kinetics
      provided the evidence of metabolic adaptations related to a specific training in
      professional cyclists with a significantly faster rate (P < 0.01) of pH return
      toward basal values (32.8 +/- 18.9 vs 10.8 +/- 6.7 mM x min(-1)). On the
      contrary, no significant difference was measured for the PCr recovery kinetics.
      At rest, PDE concentration was significantly higher in professional cyclists
      (2.50 +/- 0.80 vs 1.76 +/- 0.42 mM), likely indicating a difference regarding
      fiber-type composition. DISCUSSION: The present data demonstrated for the first
      time that the tremendous aerobic capacity in professional cyclists is linked to
      faster pH recovery kinetics after a specific cycling exercise.

PMID- 15870641
TI  - Metabolic and perceptual responses during Spinning cycle exercise.
AB  - PURPOSE: The present investigation was undertaken to compare metabolic and
      perceptual responses between exercise performed at constant intensity (CON) and
      with a Spinning protocol of variable intensity (VAR). METHOD: Fifteen subjects,
      including seven males and eight females (23 +/- 5 yr, 72 +/- 17 kg, and 171 +/-
      10 cm), underwent two experimental trials. During each trial, subjects performed
      a 30-min cycle exercise protocol that was followed by a 30-min recovery period.
      Exercise was performed at 67 +/- 3% (means +/- SD) of HR(max) in CON. In VAR, the
      similar intensity (68 +/- 4% HR(max)) was also achieved, although the protocol
      entailed alternating phases of both higher and lower intensity arranged similarly
      to what is designed for a typical Spinning workout. Oxygen uptake (VO2) and HR
      were measured at rest and throughout both exercise and recovery, whereas RPE were
      recorded during exercise only. Plasma lactate concentrations [La] were determined
      at rest, the end of exercise, and the end of recovery. RESULTS: No differences in
      average VO2, HR, and RPE were found during exercise between CON and VAR. However,
      average VO2 and HR were higher (P < 0.05) in VAR than CON (0.33 +/- 0.03 vs 0.26
      +/- 0.02 L x min(-1) and 91 +/- 3 vs 80 +/- 2 beats x min(-1), respectively).
      [La] was higher (P < 0.05) at the end of exercise in VAR than CON (7.2 +/- 0.8 vs
      2.7 +/- 0.3 mmol x L(-1)), but became similar at the end of recovery. CONCLUSION:
      An exercise regimen in which intensity varies exerts no added effect on metabolic
      and perceptual responses during exercise as long as the average intensity is kept
      the same. However, VAR resulted in a greater [latin capital V with dot above]O2
      after exercise, and this augmented postexercise oxygen consumption may be
      mediated in part by elevated plasma [La].

PMID- 15870642
TI  - Body-mass management of Australian lightweight rowers prior to and during
      competition.
AB  - PURPOSE: Although the body-mass management strategies of athletes in high
      participation weight-category sports such as wrestling have been thoroughly
      investigated, little is known about such practices among lightweight rowers. This
      study examined the body-mass management practices of lightweight rowers before
      competition and compared these with current guidelines of the International
      Federation of Rowing Association (FISA). Quantification of nutrient intake in the
      1-2 h between weigh-in and racing was also sought. METHODS: Lightweight rowers (N
      = 100) competing in a national regatta completed a questionnaire that assessed
      body-mass management practices during the 4 wk before and throughout a regatta
      plus recovery strategies after weigh-in. Biochemical data were collected
      immediately after weigh-in to validate questionnaire responses. Responses were
      categorized according to gender and age category (Senior B or younger than 23 yr
      old, i.e., U23, Senior A or OPEN, i.e., open age limit) for competition. RESULTS:
      Most athletes (male U23 76.5%, OPEN 92.3%; female U23 84.0%, OPEN 94.1%)
      decreased their body mass in the weeks before the regatta at rates compliant with
      FISA guidelines. Gradual dieting, fluid restriction, and increased training load
      were the most popular methods of body-mass management. Although the importance of
      recovery after weigh-in was recognized by athletes, nutrient intake and
      especially sodium (male U23 5.3 +/- 4.9, OPEN 7.7 +/- 5.9; female U23 5.7 +/-
      6.8, OPEN 10.2 +/- 5.4 mg x kg(-1)) and fluid intake (male U23 12.1 +/- 7.1, OPEN
      13.5 +/- 8.1; female U23 9.4 +/- 7.4, OPEN 14.8 +/- 6.9 mL x kg(-1)) were below
      current sports nutrition recommendations. CONCLUSION: Few rowers were natural
      lightweights; the majority reduced their body mass in the weeks before a regatta.
      Nutritional recovery strategies implemented by lightweight rowers after weigh-in
      were not consistent with current guidelines.

PMID- 15870643
TI  - Feasibility of using accelerometers to measure physical activity in young
      adolescents.
AB  - PURPOSE: Accelerometers may provide valid measures of physical activity, but the
      feasibility of using accelerometers with large groups of children is unknown. We
      assessed feasibility in the Eating and Activity Survey Trial (Project EAST), a
      study designed to develop valid tools to assess eating and physical activity
      patterns among middle school children. METHODS: Two hundred eighty-two Project
      EAST participants in grades 6-8 wore an accelerometer (Manufacturing
      Technologies, Inc., Fort Walton Beach, FL) for seven consecutive days. Multiple
      strategies were employed to encourage compliance and return of the accelerometer:
      1) staff demonstrated how to wear the device properly; 2) students were given
      written and verbal instructions; 3) staff visited the students twice during 7 d
      to remind them to wear the devices and return them on time; and 4) movie tickets
      were given to students who returned the accelerometers on time. RESULTS: Data
      from 27 accelerometers were lost as a result of mechanical and nontechnical
      problems, resulting in unusable data for 8.5% of students. Days of data for the
      remaining 255 students were considered incomplete if the accelerometer registered
      less than three consecutive waking hours of zero counts. The percentage of
      students with complete accelerometer data for 3-7 d of data were > or = 3 d, 92%;
      > or = 4 d, 86%; > or = 5 d, 75%; > or = 6 d, 67%; and 7 d, 50%. Twenty-eight
      students (10%) returned their accelerometers late. Overweight children were
      significantly more likely to have 7 d of complete data than nonoverweight
      children. CONCLUSION: Our findings suggest that accelerometers are acceptable to
      most students. However, researchers working with middle school students should
      carefully monitor compliance to ensure that devices are worn properly and
      regularly.

PMID- 15870644
TI  - Accelerometry and heart rate as a measure of physical fitness: proof of concept.
AB  - PURPOSE: This study focused on developing a new method to assess VO2max outside
      laboratory conditions and without the need for maximal exertion. We hypothesized
      that the combined use of accelerometry and HR monitoring, under daily life
      conditions, could provide a good estimate of physical fitness. METHODS: Twenty
      six healthy subjects (15 women, 11 men), aged 28 +/- 7 yr, performed a maximal
      incremental test on a bicycle ergometer to determine VO2max. Body composition was
      measured with underwater weighing and deuterium dilution using a three
      compartment model. A triaxial accelerometer (Tracmor) and an HR monitor were worn
      for seven consecutive days under free-living conditions. The ratio of HR to
      activity counts per minute (ACM) was used as a fitness index (HR.ACM(-1)).
      RESULTS: As hypothesized, HR.ACM(-1) was significantly correlated with VO2max.
      Using fat-free mass (FFM) (P < 0.0001), age (P = 0.025), and HR.ACM(-1) (P =
      0.021) as the independent variables, the explained variation in VO2max was 76% (P
      < 0.0001, SEE = 363 mL x min(-1)). In order to generate a prediction formula that
      is applicable in the field when no data on body composition are available, the
      same analysis was done with body mass and gender in the model instead of FFM.
      HR.ACM(-1) was significantly (P = 0.023) correlated with VO2max. The total
      explained variation of the model was 71%, with a SEE of 409 mL x min(-1), or
      13.7% of the average VO2max. CONCLUSION: After correction for body composition,
      VO2max was significantly related to HR.ACM(-1). It is, to our knowledge, the
      first tool that yields a measure of VO2max by monitoring people in their daily
      life activities without the need for a specific protocol or for maximal exertion,
      and therefore is applicable to a large variety of subjects.

PMID- 15870645
TI  - Longitudinal changes in cardiorespiratory fitness: measurement error or true
      change?

PMID- 15870655
TI  - Children as clinical research subjects.

PMID- 15870656
TI  - Reliability of the health care delivery system.

PMID- 15870657
TI  - Diet, immunity, and autistic spectrum disorders.

PMID- 15870658
TI  - Surveying euthanasia practices: methods and morality.

PMID- 15870659
TI  - Are soft drinks a scapegoat for childhood obesity?

PMID- 15870661
TI  - Preliminary diagnostic guidelines for macrophage activation syndrome complicating
      systemic juvenile idiopathic arthritis.
AB  - OBJECTIVE: To develop diagnostic guidelines for macrophage activation syndrome
      (MAS) complicating systemic juvenile idiopathic arthritis (S-JIA). STUDY DESIGN:
      We followed the classification criteria approach that is based on the comparison
      of patients with the index disease with patients with a "confusable" disease. The
      former group included 74 patients with S-JIA-associated MAS reported in the
      literature or seen by the authors; the latter group included 37 patients with S
      JIA who had 51 instances of "high disease activity" seen by the authors. The
      relative power of clinical, laboratory, and histopathologic variables in
      discriminating patients with MAS from patients with high disease activity was
      evaluated by calculating the sensitivity rate, specificity rate, area under the
      receiver operating characteristic curve, and diagnostic odds ratio (DOR). The
      combinations of variables that led to best separation between patients and
      control subjects were identified through "the number of criteria present" method.
      RESULTS: The strongest clinical discriminators were hemorrhages (DOR = 67) and
      central nervous system dysfunction (DOR = 63); the strongest laboratory
      discriminators were decreased platelet count (DOR = 1092), increased aspartate
      aminotransferase (DOR = 247), leukopenia (DOR = 70), and hypofibrinogenemia (DOR
      = 165). The best separation between patients and control subjects occurred when
      any 2 or more laboratory criteria (DOR = 1309) were simultaneously present; the
      second best performance was provided by the presence of any 2, 3, or more
      clinical and/or laboratory criteria (DOR = 765 and 743, respectively).
      CONCLUSION: We identified preliminary diagnostic guidelines for MAS complicating
      S-JIA. These guidelines deserve prospective validation.

PMID- 15870660
TI  - Use of asthma guidelines by primary care providers to reduce hospitalizations and
      emergency department visits in poor, minority, urban children.
AB  - OBJECTIVES: To determine whether an organized, citywide asthma management program
      delivered by primary care providers (PCPs) increases adherence to the National
      Asthma Education and Prevention Program (NAEPP) Asthma Guidelines and whether
      adherence to the guidelines by PCPs decreases medical services utilization in low
      income, minority children. STUDY DESIGN: Analysis of the utilization of medical
      services for a cohort of 3748 children with asthma who presented for care at one
      of six primary care urban clinics in Hartford, Connecticut, and who were enrolled
      in a disease management program (Easy Breathing) between June 1, 1998 and August
      31, 2002. RESULTS: Of the 3748 children with physician-confirmed asthma, 48% had
      persistent disease. Paid claims for inhaled corticosteroids increased 25% ( P
      <.0001) after enrollment in Easy Breathing. Provider adherence to the NAEPP
      guidelines for anti-inflammatory therapy increased from 38% to 96%. Easy
      Breathing children with asthma experienced a 35% decrease in overall
      hospitalization rates ( P <.006), a 27% decrease in asthma emergency department
      (ED) visits ( P <.01), and a 19% decrease in outpatient visits ( P <.0001).
      CONCLUSIONS: An organized, disease management program increased adherence to the
      NAEPP guidelines for anti-inflammatory use by PCPs in urban clinics. Adherence to
      this element of the guidelines by PCPs reduced hospitalizations, ED visits, and
      outpatient visits for children with asthma.

PMID- 15870662
TI  - Evaluation of an association between gastrointestinal symptoms and cytokine
      production against common dietary proteins in children with autism spectrum
      disorders.
AB  - OBJECTIVE: To evaluate an association between cytokine production with common
      dietary proteins as a marker of non-allergic food hypersensitivity (NFH) and
      gastrointestinal (GI) symptoms in young children with autism spectrum disorders
      (ASD). STUDY DESIGN: Peripheral blood mononuclear cells (PBMCs) were obtained
      from 109 ASD children with or without GI symptoms (GI [+] ASD, N = 75 and GI (-)
      ASD, N = 34], from children with NFH (N = 15), and control subjects (N = 19).
      Diarrhea and constipation were the major GI symptoms. We measured production of
      type 1 T-helper cells (Th1), type 2 T-helper cells (Th2), and regulatory
      cytokines by PBMCs stimulated with whole cow's milk protein (CMP), its major
      components (casein, beta-lactoglobulin, and alpha-lactoalbumin), gliadin, and
      soy. RESULTS: PBMCs obtained from GI (+) ASD children produced more tumor
      necrosis factor-alpha (TNF-alpha)/interleukin-12 (IL-12) than those obtained from
      control subjects with CMP, beta-lactoglobulin, and alpha-lactoalbumin,
      irrespective of objective GI symptoms. They also produced more TNF-alpha with
      gliadin, which was more frequently observed in the group with loose stools. PBMCs
      obtained from GI (-) ASD children produced more TNF-alpha/IL-12 with CMP than
      those from control subjects, but not with beta-lactoglobulin, alpha-lactoalbumin,
      or gliadin. Cytokine production with casein and soy were unremarkable.
      CONCLUSION: A high prevalence of elevated TNF-alpha/IL-12 production by GI (+)
      ASD PBMCs with CMP and its major components indicates a role of NFH in GI
      symptoms observed in children with ASD.

PMID- 15870663
TI  - Physicians' willingness to grant requests for assistance in dying for children: a
      study of hypothetical cases.
AB  - OBJECTIVE: To study the willingness of Dutch physicians to use potentially life
      shortening or lethal drugs for severely ill children. STUDY DESIGN: We asked 63
      pediatricians about their approach to 10 hypothetical cases of children with
      cancer. The age of the child (15, 11, or 6 years), the child's (explicit)
      request, and the opinion of the parents varied. Two hypothetical cases were also
      presented to 125 general practitioners and 208 clinical specialists. RESULTS:
      Most pediatricians were willing to increase morphine in all cases. A total of 48%
      to 60% of pediatricians were willing to use lethal drugs in children at the
      child's request, when the parents agreed; when parents requested ending of life
      of their unconscious child, 37% to 42% of pediatricians were willing; 13% to 28%
      of pediatricians were willing when parents did not agree with their child's
      request. General practitioners and clinical specialists were as willing as
      pediatricians to use lethal drugs at the child's request, but less willing to
      grant a request of parents for their unconscious child. CONCLUSIONS: Many Dutch
      pediatricians are willing to use potentially life-shortening or lethal drugs for
      children. The legal limit of 12 years, as the age under which voluntary
      euthanasia is forbidden, is not fully supported by Dutch physicians.

PMID- 15870664
TI  - Two-year follow-up results for Hip-Hop to Health Jr.: a randomized controlled
      trial for overweight prevention in preschool minority children.
AB  - OBJECTIVES: To assess the impact of a culturally proficient dietary/physical
      activity intervention on changes in body mass index (BMI) (kg/m 2 ). STUDY
      DESIGN: Randomized controlled trial (Hip-Hop to Health Jr.) conducted between
      September 1999 and June 2002 in 12 Head Start preschool programs in Chicago,
      Illinois. RESULTS: Intervention children had significantly smaller increases in
      BMI compared with control children at 1-year follow-up, 0.06 vs 0.59 kg/m 2 ;
      difference -0.53 kg/m 2 (95% CI -0.91 to -0.14), P = .01; and at 2-year follow
      up, 0.54 vs 1.08 kg/m 2 ; difference -0.54 kg/m 2 (95% CI -0.98 to -0.10), P =
      .02, with adjustment for baseline age and BMI. The only significant difference
      between intervention and control children in food intake/physical activity was
      the Year 1 difference in percent of calories from saturated fat, 11.6% vs 12.8% (
      P = .002). CONCLUSIONS: Hip-Hop to Health Jr. was effective in reducing
      subsequent increases in BMI in preschool children. This represents a promising
      approach to prevention of overweight among minority children in the preschool
      years.

PMID- 15870665
TI  - Improved outcomes of outborn preterm infants if admitted to perinatal centers
      versus freestanding pediatric hospitals.
AB  - OBJECTIVES: To examine whether admission hospital type (13 perinatal centers vs 4
      freestanding pediatric hospitals) was associated with differences in risk and
      illness severity adjusted mortality and morbidity among outborn preterm infants.
      STUDY DESIGN: Records of singleton outborn infants < or =32 weeks' gestational
      age (n = 605) admitted to 17 tertiary level neonatal intensive care units
      participating in the Canadian Neonatal Network for the period 1996 to 1997 were
      examined. RESULTS: Outborn infants admitted to freestanding pediatric hospitals
      were at higher risk of death (adjusted odds ratio [AOR], 2.25; 95% confidence
      interval [CI], 1.20, 4.20), nosocomial infection (AOR, 2.48; 95% CI, 1.64, 3.73),
      and oxygen dependency at 28 days of age (AOR, 1.77; 95% CI, 1.14, 2.75) when
      compared with outborn infants admitted to perinatal centers. CONCLUSIONS: After
      adjustment for perinatal risks and admission illness severity, outborn infants
      had better outcomes if they were admitted to perinatal centers compared with
      freestanding pediatric hospitals.

PMID- 15870666
TI  - Pretreatment cortisol values may predict responses to hydrocortisone
      administration for the prevention of bronchopulmonary dysplasia in high-risk
      infants.
AB  - OBJECTIVES: To investigate the effect of hydrocortisone treatment on survival
      without bronchopulmonary dysplasia (BPD) and to study whether serum cortisol
      concentrations predict the response. STUDY DESIGN: We performed a randomized,
      placebo-controlled trial on infants with gestation < or =30 weeks, body weight of
      501 to 1250 g, and respiratory failure. Hydrocortisone was started before 36
      hours of age and given for 10 days at doses from 2.0 to 0.75 mg/kg per day.
      Shortly before hydrocortisone treatment, basal and stimulated (ACTH, 0.1
      microg/kg) serum cortisols were measured. RESULTS: The study was discontinued
      early, because of gastrointestinal perforations in the hydrocortisone group (4/25
      vs 0/26, P = .05); 3 of the 4 had received indomethacin/ibuprofen. The incidence
      of BPD (28% vs placebo 42%, P = 0.28) tended to be lower, and patent ductus
      arteriosus (36% vs 73%, P = .01) was lower in the hydrocortisone group. The
      hydrocortisone-treated infants with serum cortisol concentrations above the
      median had a high risk of gastrointestinal perforation. In infants with cortisol
      values below the median, hydrocortisone treatment increased survival without BPD.
      CONCLUSIONS: Serum cortisol concentrations measured shortly after birth may
      identify those very high-risk infants who may benefit from hydrocortisone
      supplementation.

PMID- 15870667
TI  - Neonatal intubation: success of pediatric trainees.
AB  - OBJECTIVES: To review the success of pediatric trainees for neonatal intubation
      over a 10-year interval at a single academic center. STUDY DESIGN: We reviewed a
      database of all neonatal intubations designed as a quality assurance process at
      our institution. Respiratory care practitioners recorded the number of attempts
      at the time of each procedure. Attempts were defined as each time a laryngoscope
      was placed in the baby's mouth. Success rates were calculated as the number of
      successful intubations divided by the attempts. RESULTS: From January 1992
      through September 2002, 5051 successful intubations with 9190 attempts were
      performed by all practitioners. Pediatric residents intubated neonates
      successfully on 1676 occasions requiring 3719 attempts. The median success rates
      were 33% for pediatric level (PL)1 residents; 40% for PL2 and PL3 residents, and
      68% for neonatal fellows ( P < .001). The success rates for residents who had
      more than 20 total attempts versus those who had fewer than 20 attempts were 49%
      versus 37% ( P < .001). CONCLUSIONS: Developing proficiency at intubation
      requires a significant amount of experience. Current pediatric residents at our
      institution have inadequate opportunity to achieve consistent success.

PMID- 15870669
TI  - Initial presentation of childhood-onset systemic lupus erythematosus: a French
      multicenter study.
AB  - OBJECTIVE: To describe the clinical and laboratory manifestations of childhood
      onset systemic lupus erythematosus (SLE) at presentation. STUDY DESIGN: This
      retrospective French multicenter study involved 155 patients in whom SLE
      developed before the age of 16 years. Mean patient age at onset was 11.5 +/- 2.5
      years (range, 1.5-16 years). The female to male ratio was 4.5. RESULTS: The most
      common initial manifestations were hematologic (72%), cutaneous (70%),
      musculoskeletal (64%), renal (50%), and fever (58%). Thirty-two percent of
      children had atypical symptoms, mainly including abdominal involvement in 26
      patients, which lead to negative laparotomy results for presumed appendicitis.
      Severe renal, neurologic, hematologic, abdominal, cardiac, pulmonary, thrombotic,
      and/or cutaneous manifestations occurred within the first month after the
      diagnosis in 40% of patients. The mean erythrocyte sedimentation rate was 72 +/-
      29 mm/h, and the mean C-reactive protein value 22 +/- 21 mg/L. Antinuclear
      antibodies an, anti-double stranded DNA antibodies, and low C3 or C4 level were
      retrieved in 97%, 93%, and 78 % of patients, respectively. CONCLUSION: Initial
      manifestations of childhood-onset SLE are diverse and often severe. The diagnosis
      of SLE should be promptly considered in any febrile adolescent with unexplained
      organ involvement, especially when associated with an increased erythrocyte
      sedimentation rate.

PMID- 15870668
TI  - Glutamine supplement with parenteral nutrition decreases whole body proteolysis
      in low birth weight infants.
AB  - OBJECTIVES: To examine the effect of supplemental glutamine (0.6 g.kg -1 .d -1 )
      on whole body protein/nitrogen and glutamine kinetics in low birth weight (LBW)
      infants receiving parenteral nutrition in the immediate neonatal period. STUDY
      DESIGN: Premature infants < or =32 weeks gestation with a birth weight from 694
      to 1590 g were randomly assigned to either a glutamine-supplemented group (n =
      10) or to a control group (n = 10). Tracer isotope studies were performed when
      the infants were 6 to 7 days old and had been receiving an amino acid intake of
      approximately 3.0 g.kg -1 .d -1 for at least 3 days. Whole body glutamine and
      nitrogen kinetics were measured with [5-15N]glutamine, [2H5]phenylalanine, [1
      13C, 15 N]leucine, [15N2]urea, and GC-mass spectrometry. RESULTS: Supplemental
      glutamine was associated with a lower rate of appearance of glutamine ( P =
      .003), phenylalanine ( P = .001), and leucine C ( P = .003). There was no
      significant difference in leucine N turnover, urea turnover and plasma cortisol,
      and C-reactive protein levels in the 2 groups. CONCLUSION: Parenteral glutamine
      supplement in LBW infants was associated with lower whole-body protein breakdown.
      Because the decrease in whole body proteolysis is associated with protein
      accretion, parenteral glutamine supplement may be beneficial in selected
      populations of LBW infants.

PMID- 15870670
TI  - Immunodeficiency in children with acute lymphoblastic leukemia after completion
      of modern aggressive chemotherapeutic regimens.
AB  - OBJECTIVE: To determine the prevalence, duration, and a potential cause of
      humoral defect(s) in children with acute lymphoblastic leukemia (ALL) at least 1
      year after completion of chemotherapy. STUDY DESIGN: Antibody titers for mumps,
      rubeola, rubella, tetanus and diphtheria toxoid, poliovirus serotypes 1, 2,and 3,
      Haemophilus influenzae type b, varicella, and hepatitis B were obtained from 100
      children with ALL. Children with non-protective titers to these microbial
      antigens were re-vaccinated and re-studied after anamnestic vaccine challenge.
      RESULTS: The percent of children with ALL who had protective titers was markedly
      less than that anticipated for immunized control subjects. Longitudinally, many
      titers fluctuate between protective and non-protective antibody responses after
      re-immunization. The chemotherapy protocol used did not affect the ability of
      these children to express protective antibody responses. T-, B-, and NK-cell
      numbers and proliferative responses to mitogens were all normal. Age correlated
      with titer results for certain vaccines. CONCLUSIONS: Children in remission from
      ALL have a high prevalence of humoral immune defects that are not related to any
      specific chemotherapy regimen. This antibody deficiency may place children with
      ALL at risk for the development of these bacterial and viral diseases, even after
      completion of chemotherapy. Pediatricians, oncologists, or both should
      periodically monitor humoral immunity after chemotherapy and re-vaccinate these
      children, as needed, to ensure prolonged immunoprotection.

PMID- 15870671
TI  - Infliximab treatment for refractory Kawasaki syndrome.
AB  - OBJECTIVE: To evaluate the use of tumor necrosis factor (TNF)-alpha blockade for
      treatment of patients with Kawasaki syndrome (KS) who fail to become afebrile or
      who experience persistent arthritis after treatment with intravenous gamma
      globulin (IVIG) and high-dose aspirin. STUDY DESIGN: Cases were retrospectively
      collected from clinicians throughout the United States who had used infliximab, a
      chimeric murine/human immunoglobulin (Ig)G1 monoclonal antibody that binds
      specifically to human TNF-alpha-1, for patients with KS who had either persistent
      arthritis or persistent or recrudescent fever > or =48 hours following infusion
      of 2 g/kg of IVIG. RESULTS: Response to therapy with cessation of fever occurred
      in 13 of 16 patients. C-reactive protein (CRP) level was elevated in all but one
      patient before infliximab infusion, and the level was lower following infusion in
      all 10 patients in whom it was re-measured within 48 hours of treatment. There
      were no infusion reactions to infliximab and no complications attributed to
      infliximab administration in any of the patients. CONCLUSION: The success of TNF
      alpha blockade in this small series of patients suggests a central role of TNF
      alpha in KS pathogenesis. Controlled, randomized clinical trials are warranted to
      determine the role of anti-TNF-alpha therapy in KS.

PMID- 15870672
TI  - Policy issues for expanding newborn screening programs: the cystic fibrosis
      newborn screening experience in the United States.
AB  - OBJECTIVE: To describe the screening approaches and implementation strategies for
      cystic fibrosis newborn screening in the 12 programs that were offered in 11
      states in 2002. STUDY DESIGN: Telephone interviews conducted in the spring of
      2003 with program representatives in the 11 states. Screening approaches were
      defined in four overlapping categories: state mandated screening, state-wide
      offering, hospital based screening, and screening with informed consent. RESULTS:
      Screening was state mandated in seven states but was routinely offered to most
      infants in nine states. The primary care provider or hospital determined if
      screening was done in three states (four programs). Informed consent was
      explicitly documented in two states. In five programs, immunoreactive trypsinogen
      exclusively was used to identify at-risk infants. In seven programs, a second
      tier DNA test was also used, but these programs each had distinct strategies. In
      only two programs where DNA testing was performed and normal sweat tests
      indicated carrier status, were results routinely provided to parents "in person"
      at a CF center. CONCLUSION: The diversity of approaches for screening approaches
      and strategies has advantages for future policy decisions, provided that data
      about the clinical and psychosocial impact of screening from these programs are
      collected and disseminated. As additional states determine that the resources are
      available, programs can be designed with a more favorable benefit/risk balance as
      a result of the successes and challenges faced by other states.

PMID- 15870673
TI  - Phenotypic and genetic characterization of patients with features of "nonclassic"
      forms of cystic fibrosis.
AB  - OBJECTIVE: To determine which features of incomplete or "nonclassic" forms of
      cystic fibrosis (CF) are associated with deleterious CF transmembrane conductance
      regulator gene ( CFTR ) mutations, and to explore other etiologies for features
      not associated with deleterious CFTR mutations. STUDY DESIGN: Clinical features
      were compared between 57 patients with deleterious mutations in each CFTR and 63
      with no deleterious mutations. The Shwachman Bodian Diamond syndrome gene ( SBDS
      ) was sequenced to search for mutations in patients with no deleterious CFTR
      mutations and steatorrhea to determine if any had unrecognized Shwachman-Diamond
      syndrome (SDS). RESULTS: The presence of a common CF-causing mutation, absence of
      the vas deferens, and Pseudomona aeruginosa in the sputum correlated with the
      presence of two deleterious CFTR mutations, whereas sweat chloride concentration,
      diagnostic criteria for CF, and steatorrhea did not. However, sweat chloride
      concentration correlated with CFTR mutation status in patients infected with P
      aeruginosa. One patient had disease-causing mutations in each SBDS . CONCLUSIONS:
      Presence of a common CF-causing mutation, absence of the vas deferens and/or P
      aeruginosa infection in a patient with features of nonclassic CF are predictive
      of deleterious mutations in each CFTR , whereas steatorrhea in the same context
      is likely to have etiologies other than CF transmembrane conductance regulator
      (CFTR) dysfunction.

PMID- 15870674
TI  - Epidemiology of cystic fibrosis-related diabetes.
AB  - OBJECTIVES: Cystic fibrosis-related diabetes (CFRD) has emerged as an important
      complication of CF. To better understand who is at risk of developing CFRD, to
      gain insight into the impact of CFRD on pulmonary and nutritional status, and to
      assess the association of CFRD with various practice patterns and comorbid
      conditions, we characterized the Epidemiologic Study of Cystic Fibrosis (ESCF)
      patient population. STUDY DESIGN: Analyses were performed on the 8247 adolescents
      and adults who were evaluated at one of 204 participating sites during 1998. CFRD
      was defined as the use of insulin or an oral hypoglycemic agent at any time
      during the year. RESULTS: Previously reported risk factors for CFRD including
      age, gender (female), and pancreatic insufficiency were confirmed in this study.
      Patients with CFRD had more severe pulmonary disease, more frequent pulmonary
      exacerbations, and poorer nutritional status as compared with those without
      diabetes. CFRD also was associated with liver disease. CONCLUSIONS: CFRD is a
      common complication in adolescents and adults that is associated with more severe
      disease.

PMID- 15870677
TI  - The global spread of type 2 diabetes mellitus in children and adolescents.

PMID- 15870678
TI  - Genetic syndromes mimic congenital infections.
AB  - Genetic syndromes that mimic congenital infection are important to recognize
      because of the associated risk of recurrence. We describe two brothers born to
      consanguineous parents with clinical features suggestive of intrauterine
      infection but with negative serologic investigations. Our observations suggest
      that Aicardi-Goutieres syndrome (AGS) and pseudo-TORCH syndrome likely represent
      the same disorder.

PMID- 15870679
TI  - Hyperinsulinism of infancy associated with a novel splice site mutation in the
      SCHAD gene.
AB  - Fatty acids play an important role in regulating insulin secretion, but the
      mechanisms are unclear. We report a case of a novel splice site mutation in the
      short-chain 3-hydroxyacyl-CoA dehydrogenase (SCHAD) gene associated with
      hyperinsulinism. This mutation resulted in a nearly complete absence of
      immunoreactive protein and a decrease in fibroblast SCHAD activity.

PMID- 15870676
TI  - Population-based study of incidence and risk factors for cerebral edema in
      pediatric diabetic ketoacidosis.
AB  - OBJECTIVES: To determine incidence, outcomes, and risk factors for pediatric
      cerebral edema with diabetic ketoacidosis (CEDKA) in Canada. STUDY DESIGN: This
      was a case-control study nested within a population-based active surveillance
      study of CEDKA in Canada from July 1999 to June 2001. Cases are patients with DKA
      <16 years of age with cerebral edema. Two unmatched control subjects per case are
      patients with DKA without cerebral edema. RESULTS: Thirteen cases of CEDKA were
      identified over the surveillance period for an incidence rate of 0.51%; 23% died
      and 15% survived with neurologic sequelae. CEDKA was present at initial
      presentation of DKA in 19% of cases. CEDKA was associated with lower initial
      bicarbonate ( P = .001), higher initial urea ( P = .001), and higher glucose at
      presentation ( P = .014). Although there was a trend to association with higher
      fluid rates and treatment with bicarbonate, these were not independent
      predictors. CONCLUSIONS: CEDKA remains a significant problem with a high
      mortality rate. No association was found between the occurrence of CEDKA and
      treatment factors. The presence of cerebral edema before treatment of DKA and the
      association with severity of illness suggest that prevention of DKA is the key to
      avoiding this devastating complication.

PMID- 15870680
TI  - Prophylactic ibuprofen in premature infants: a multicentre, randomised, double
      blind, placebo-controlled trial.

PMID- 15870681
TI  - Randomized, controlled trial of slow versus rapid feeding volume advancement in
      preterm infants.

PMID- 15870682
TI  - Oral probiotics reduce the incidence and severity of necrotizing enterocolitis in
      very low birth weight infants.

PMID- 15870685
TI  - Hypereosinophilia in red scaly infants with scabies.

PMID- 15870686
TI  - Selecting families for successful insulin pump therapy.

PMID- 15870687
TI  - Obesity and asthma.

PMID- 15870689
TI  - Interaction between Brk kinase and insulin receptor substrate-4.
AB  - Breast tumor kinase (Brk) is a member of the Frk family of nonreceptor tyrosine
      kinases that is overexpressed in a high percentage of human breast tumors. The
      downstream substrates and effectors of Brk remain largely unidentified. In this
      study, we carried out immunoprecipitation and mass spectrometry experiments to
      identify new Brk binding partners. One interacting protein was insulin receptor
      substrate 4 (IRS-4), a member of the IRS family. We confirmed that Brk associates
      with IRS-4 in resting and insulin-like growth factor 1 (IGF-1)-stimulated HEK 293
      cells. The SH3 and SH2 domains of Brk are both involved in the association. The
      tyrosine phosphorylation of Brk increases after stimulation with IGF-1, and in
      MCF-7 breast cancer cells we show that the presence of IRS-4 enhances this
      effect. Finally, we demonstrate that endogenous Brk and IRS-4 interact in A431
      human epidermoid carcinoma cells.

PMID- 15870688
TI  - Haploinsufficiency identifies STAT5 as a modifier of IL-7-induced lymphomas.
AB  - The requirement for receptor components and the signalling effector, signal
      transducer and activator of transcription (STAT) 5A/5B, was assessed genetically
      in a lymphoma development model induced by interleukin-7 (IL-7). This growth
      factor for T- and B-cell progenitors and mature lymphocytes activates survival
      and proliferative pathways including Bcl-2, phosphatidylinositol-3 kinase and
      STAT5. Overexpression of IL-7 in vivo causes early mortality from lymphoma
      development. Mice overexpressing IL-7 that were heterozygous for the IL-7Ralpha
      subunit showed improved survival compared to wild-type mice. In addition,
      STAT5A/5B+/- compound heterozygous mice with one targeted allele each of STAT5A
      and STAT5B showed striking amelioration of IL-7-induced mortality and disease
      development. STAT5A/5B+/- compound heterozygous mice were otherwise normal in
      stem cell and lymphocyte development and cellularity. Lower STAT5 protein levels
      accompanied the reduction in STAT5A/5B copy number, which suggests that STAT5
      haploinsufficiency is a modifier of IL-7 signal strength.

PMID- 15870690
TI  - Shc3 affects human high-grade astrocytomas survival.
AB  - A selective switch from expression of Shc1 gene to Shc3 occurs with maturation of
      neuronal precursors into postmitotic neurons. Previous studies showed that in the
      embryo, Shc1 is maximally expressed in dividing CNS stem cells while it is
      silenced in mature neurons, where it is replaced by Shc3. Under normal conditions
      Shc3 is never expressed by glial cells. We now show that in human astrocytomas
      and glioblastomas, the normal pattern of expression of Shc1/Shc3 is totally
      subverted, both proteins being present at the same time and in the same cells.
      Our data indicate that Shc3 is maximally expressed, together with Shc1, in
      glioblastoma, a highly proliferative tumor with little, if any, indication of
      neuronal differentiation. In primary cultures of glioblastoma, tumor cells
      maintain Shc1 expression but downregulate Shc3. Analysis of the phosphorylation
      status of Shc3 in human glioblastoma tumor samples in vivo indicates that it is
      tyrosine phosphorylated. Finally, we found that the expression of truncated
      variants of Shc3 with dominant-negative effects in human high-grade glioma cells
      that maintain Shc3 expression in vitro leads to a decreased Akt posphorylation
      and increased apoptosis, thus resulting in impaired survival of the transfected
      cells. These data suggest that Shc molecules play an important role in
      glioblastoma cell growth and survival.

PMID- 15870691
TI  - Epigenetic silencing of TCEAL7 (Bex4) in ovarian cancer.
AB  - Epigenetic silencing by hypermethylation of CpGs represents a mechanism of
      inactivation of tumor suppressors. Here we report on the cloning of a novel
      candidate tumor suppressor gene TCEAL7 inactivated by methylation in ovarian
      cancer. TCEAL codes for a 1.35 kb transcript that was previously reported to be
      downregulated in ovarian cancer by cDNA microarray and suppression subtraction
      cDNA (SSH) analyses. This report focuses on the elucidation of mechanisms
      associated with TCEAL7 downregulation. Expression of TCEAL7 is downregulated in a
      majority of ovarian tumors and cancer cell lines but induced by 5-aza-2'
      deoxycytidine treatment in a dose-dependant manner, implicating methylation as a
      mechanism of TCEAL7 inactivation. Sequence analyses of bisufite-modified genomic
      DNA from somatic cell hybrids with either the active or the inactive human X
      chromosome reveal that TCEAL7 is subjected to X chromosome inactivation. Loss of
      TCEAL7 expression in primary tumors and cell lines correlates with methylation of
      a CpG site within the promoter. In vitro methylation of the CpG site suppresses
      promoter activity whereas selective demethylation of the SmaI site attenuates the
      suppression. Finally, re-expression of TCEAL7 in cancer cell lines induces cell
      death and reduces colony formation efficiency. These data implicate TCEAL7 as a
      cell death regulatory protein that is frequently inactivated in ovarian cancers,
      and suggest that it may function as a tumor suppressor.

PMID- 15870692
TI  - Methylation adjacent to negatively regulating AP-1 site reactivates TrkA gene
      expression during cancer progression.
AB  - Nerve growth factor and its high-affinity receptor TrkA are thought to be
      involved in the progression of various cancers. This study investigated the
      mechanism that regulates aberrant or increased TrkA expression in various cancer
      cell lines and in the course of pancreatic cancer progression. We found that the
      negative cis-acting AP-1-like sequence TGAGCGA was located in the 5'-untranslated
      region of the TrkA gene. Sodium bisulfite mapping revealed that steady-state TrkA
      expression correlated positively with the accumulation of methylated CpG around
      the AP-1-like site. Electrophoretic mobility shift assay showed that the AP-1
      like site was bound mainly by c-Jun homodimers; the binding was directly blocked
      by Sss I methylase-induced methylation or by an excess of oligonucleotides
      containing consensus AP-1 sequences. Consequently, activation of TrkA gene
      expression by methylation was considered to be caused by the direct interference
      of c-Jun binding to the negatively regulating AP-1-like site. Furthermore, the
      accumulation of methylated CpG around the AP-1-like site was also observed with
      increased TrkA immunohistochemical staining in cases of advanced pancreatic
      adenocarcinoma with extensive perineural invasion. Unlike global methylation at
      CpG islands that leads to gene silencing, specific methylation at non-CpG islands
      would play a crucial epigenetic role in the versatility and plasticity of TrkA
      expression during cancer progression.

PMID- 15870693
TI  - Gene expression-based classification of nonseminomatous male germ cell tumors.
AB  - Male adult germ cell tumors (GCTs) comprise two major histologic groups:
      seminomas and nonseminomas. Nonseminomatous GCTs (NSGCTs) can be further divided
      into embryonal carcinoma (EC), teratoma (T), yolk sac tumor (YS), and
      choriocarcinoma (CC) on the basis of the lineage differentiation that they
      exhibit. NSGCTs frequently present as mixed tumors consisting of two or more
      histological subtypes, often limiting correlative studies of clinical and
      molecular features to histology. We sought to develop a molecular classifier that
      could predict the predominant histologic subtype within mixed NSGCT tumor
      samples. The expression profiles of 84 NSGCTs (42 pure and 42 mixed) and normal
      age-matched testes were obtained using Affymetrix microarrays. Using prediction
      analysis for microarrays, we identified 146 transcripts that classified the
      histology of pure NSGCTs samples with 93% accuracy. When applied to mixed NSGCTs,
      the classifier predicted a histology that was consistent with one of the reported
      components in 93% of cases. Among the predictive transcripts were CGB (high in
      CC), LCN2 (high in T), BMP2 (high in YS), and POU5F1 (high in EC). Thus, the
      expression-based classifier accurately assigned a single predominant histology to
      mixed NSGCTs, and identified transcripts differentially expressed between
      histologic components with relevance to NSGCT differentiation.

PMID- 15870694
TI  - Identification and functional characterization of the candidate tumor suppressor
      gene TRIT1 in human lung cancer.
AB  - tRNA-isopentenyltransferase (tRNA-IPT) catalyses the addition of N6
      isopentenyladenosine (i6A) on residue 37 of tRNA molecules that bind codons
      starting with uridine. Post-transcriptional modifications of tRNA molecules have
      been demonstrated to be essential in maintaining the correct reading frame of the
      translational machinery, thus improving fidelity and efficiency of protein
      synthesis. We show here that the human tRNA-isopentenyltransferase (TRIT1) gene
      encodes a complex pattern of mRNA variants through alternative splicing in both
      normal and tumor lung tissue and that the nonsense suppressor activity of tRNA
      IPT is maintained only in the full-length mRNA isoform, as revealed by gene
      complementation in yeast. Expression of the full-length transcript was down
      regulated 6-14-fold in lung adenocarcinomas as compared to normal lung tissue.
      A549 lung cancer cells transfected to express the functional TRIT1 gene formed
      significantly smaller colonies with reduced scattering on the edges and had only
      limited ability to induce tumors in nude mice. Our findings raise the possibility
      of TRIT1 as a candidate lung tumor suppressor.

PMID- 15870696
TI  - Multiple mechanisms induce transcriptional silencing of a subset of genes,
      including oestrogen receptor alpha, in response to deacetylase inhibition by
      valproic acid and trichostatin A.
AB  - Valproate (VPA) and trichostatin A (TSA), inhibitors of zinc-dependent
      deacetylase activity, induce reduction in the levels of mRNA encoding oestrogen
      receptor-alpha (ERalpha), resulting in subsequent clearance of ERalpha protein
      from breast and ovarian cell lines. Inhibition of oestrogen signalling may
      account for the endocrine disorders, menstrual abnormalities, osteoporosis and
      weight gain that occur in a proportion of women treated with VPA for epilepsy or
      for bipolar mood disorder. Transcriptome profiling revealed that VPA and TSA also
      modulate the expression of, among others, key regulatory components of the cell
      cycle. Meta-analysis of genes directly responsive to oestrogen indicates that VPA
      and TSA have a generally antioestrogenic profile in ERalpha positive cells.
      Concomitant treatment with cycloheximide prevented most of these changes in gene
      expression, including downregulation of ERalpha mRNA, indicating that a limited
      number of genes signal a hyperacetylated state within cells. Three members of the
      NAD-dependent deacetylases, the sirtuins, are upregulated by VPA and by TSA and
      sirtuin activity contributes to loss of ERalpha expression. However, prolonged
      inhibition of the sirtuins by sirtinol also induces loss of ERalpha from cells.
      Mechanistically, we show that VPA invokes reversible promoter shutoff of the
      ERalpha, pS2 and cyclin D1 promoters, by inducing recruitment of methyl cytosine
      binding protein 2 (MeCP2) with concomitant exclusion of the maintenance methylase
      DNMT1. Furthermore, we demonstrate that, in the presence of VPA, local DNA
      methylation, deacetylation and demethylation of activated histones and
      recruitment of inhibitory complexes occurs on the pS2 promoter.

PMID- 15870695
TI  - An N-terminal region of translationally controlled tumor protein is required for
      its antiapoptotic activity.
AB  - Bcl-xL plays a critical role in maintaining cell survival. However, the
      relationship between the potential interaction of Bcl-xL with other cytosolic
      proteins and the regulation of cell survival remains incompletely defined. We
      have identified translationally controlled tumor protein (TCTP), a
      multifunctional protein, as a novel antiapoptotic Bcl-xL-interacting protein.
      TCTP interacted in vivo and in vitro with Bcl-xL, and their sites have been
      mapped to an N-terminal region of TCTP and the Bcl-2 homology domain 3 of Bcl-xL.
      Consistent with a role in maintaining T-cell survival during activation, TCTP was
      significantly upregulated in murine T cells activated by T-cell antigen receptor
      (TCR) ligation and CD28 costimulation, which was correlated with the upregulation
      of Bcl-xL in activated T cells. Moreover, downregulation of TCTP expression by
      antisense technology in T cells results in the increase of T-cell apoptosis.
      Furthermore, the N-terminal region of TCTP was required for its ability to
      inhibit apoptosis. In conclusion, this study has demonstrated that an N-terminal
      region of a cytosolic protein, TCTP, is required for its binding to Bcl-xL and
      for its antiapoptotic activity.

PMID- 15870697
TI  - Expression of estrogen receptor alpha, retinoic acid receptor alpha and cellular
      retinoic acid binding protein II genes is coordinately regulated in human breast
      cancer cells.
AB  - Human breast cancer cell lines expressing the estrogen receptor alpha (ERalpha),
      all-trans-retinoic acid (ATRA) receptor alpha (RARalpha) and cellular retinoic
      acid binding protein II (CRABPII) genes are sensitive to ATRA-mediated growth
      inhibition. To study the relationship among ERalpha, RARalpha and CRABPII
      expression, the protein levels of each member were compared in five breast cancer
      cell lines (T47D, MCF-7, ZR-75-1, Hs587 T and MDA-MB-231 cells) and two
      immortalized nontumorigenic breast epithelial cell lines (MTSV1.7 and MCF-10A).
      ERalpha, RARalpha and CRABPII proteins were detected in T47D, MCF-7 and ZR-75-1
      cells but not in other tested cell lines. RARalpha and CRABPII proteins were
      either reduced or undetectable in T47D/C4:2W and MCF-7/ADR cells with lost
      expression of ERalpha. Estradiol increased and anti-estrogens (tamoxifen and ICI
      164,384) downregulated the expression of both RARalpha and CRABPII proteins in
      T47D and MCF-7 cells. RARalpha antagonist Ro-41-5253 inhibited CRABPII
      expression, but not RARalpha expression in estradiol-treated T47D and MCF-7
      cells. Suppression of ERalpha by small interfering RNA (siRNA) reduced RARalpha
      and CRABPII gene expression and siRNA suppression of RARalpha reduced CRABPII
      expression while having no effect on ERalpha in T47D cells. Transient
      transfection of either RARalpha or ERalpha expression vectors increased CRABPII
      expression in MDA-MB-231 cells but only RARalpha, not ERalpha, activated hCRABPII
      promoter reporter. These results indicate that there is a gene activation pathway
      in which ERalpha drives RARalpha transcription and RARalpha drives CRABPII
      transcription in ERalpha-positive human breast cancer cells.

PMID- 15870698
TI  - Oncogenic Ras-mediated downregulation of Gadd153/CHOP is required for Ras-induced
      cellular transformation.
AB  - Oncogenic Ras proteins transform cells via multiple downstream signaling cascades
      that are important for cell proliferation and survival. Gadd153, also known as
      CHOP, is a growth inhibitory and proapoptotic protein and its expression is
      upregulated by many agents that induce apoptosis. Here, we report our novel
      findings that oncogenic Ras downregulates Gadd153 expression at both protein and
      mRNA levels and that such downregulation occurs, at least in part, via decreases
      in GADD153 mRNA stability. Gadd153 downregulation is specific to oncogenic Ras
      since another oncogenic family member R-Ras2/TC21 does not downregulate Gadd153.
      We further demonstrate that the expression of exogenous Gadd153 interferes with
      Ras-induced oncogenic transformation, which suggests that downregulation of
      Gadd153 appears to be an important mechanism by which oncogenic Ras promotes
      cellular transformation. Thus, oncogenic Ras-mediated cellular transformation
      also involves downmodulation of important molecules such as Gadd153 that
      negatively regulate cell growth and survival.

PMID- 15870699
TI  - Tyrosine phosphorylation of paxillin affects the metastatic potential of human
      osteosarcoma.
AB  - To acquire information on signal alteration corresponding to the changes in
      metastatic potential, we analysed protein tyrosine phosphorylation of low- and
      high-metastatic human osteosarcoma HuO9 sublines, which were recently established
      as the first metastatic model of human osteosarcoma. Tyrosine phosphorylation of
      proteins around 60, 70, and 120-130 kDa was enhanced in high-metastatic sublines.
      Among these proteins, the protein around 70 kDa, which was most remarkably
      phosphorylated, was identified as paxillin, a scaffold protein in integrin
      signaling. Activity of Src family kinase correlated well with metastatic
      potential, and a Src family kinase inhibitor, PP2, not only abolished tyrosine
      phosphorylation of paxillin but also impaired the motility of high-metastatic
      sublines. The expression of paxillin was also elevated in high-metastatic
      sublines, and knocking down of paxillin expression by RNAi method resulted in
      attenuated motility of high-metastatic cells. We also demonstrated that the
      phosphorylated form of paxillin is essential for the migration-promoting effect
      in human osteosarcoma. These findings suggest that enhanced activity of Src
      family kinases and overexpression of paxillin synergistically contribute to the
      high metastatic potential of human osteosarcoma through the hyperphosphorylation
      of paxillin.

PMID- 15870700
TI  - Chromosome 5p aberrations are early events in lung cancer: implication of glial
      cell line-derived neurotrophic factor in disease progression.
AB  - Lung cancer is the most widely diagnosed malignancy in the world. Understanding
      early-stage disease will give insight into its pathogenesis. Despite the fact
      that pre-invasive lesions are challenging to isolate, and often yield
      insufficient DNA for the analysis of multiple loci, genomic profiling of such
      lesions will lead to the discovery of causal genetic alterations, which may be
      otherwise masked by the gross instability associated with tumors. In this study,
      we report the identification of multiple early genetic events on chromosome 5p in
      lung cancer progression. Using a high-resolution 5p-specific genomic array, which
      contains a tiling path of DNA segments for comparative genomic hybridization,
      nine novel minimal regions of loss and gain were discovered in bronchial
      carcinoma in situ (CIS) specimens. Within these regions we identified two
      candidate genes novel to lung cancer. The 0.27 Mbp region at 5p15.2 contains a
      single gene, Triple Functional Domain, which we determined to be differentially
      expressed in tumors. The 0.34 Mbp region at 5p13.2 contains Glial Cell Line
      Derived Neurotrophic Factor (GDNF), which is a ligand for the RET oncogene
      product and is normally expressed during lung development (but absent in adult
      lung tissue). Our data showed not only that GDNF is overexpressed at the
      transcript level in squamous non-small-cell lung carcinoma, but also that the
      GDNF protein is present in early-stage lesions. Reactivation of the fetal lung
      expressed GDNF in early lesions and its amplification in CIS suggests an early
      role in tumorigenesis. These results highlight the value of examining the genomes
      of pre-invasive stages of cancer at tiling resolution.

PMID- 15870701
TI  - Oocyte-based screening of cytokinesis inhibitors and identification of
      pectenotoxin-2 that induces Bim/Bax-mediated apoptosis in p53-deficient tumors.
AB  - In this study, we demonstrate that a loss of p53 sensitizes tumor cells to actin
      damage. Using a novel oocyte-based screening system, we identified natural
      compounds that inhibit cytokinesis. Among these, pectenotoxin-2 (PTX-2), which
      was first identified as a cytotoxic entity in marine sponges, which depolymerizes
      actin filaments, was found to be highly effective and more potent to activate an
      intrinsic pathway of apoptosis in p53-deficient tumor cells compared to those
      with functional p53 both in vitro and in vivo. Other agents that depolymerize or
      knot actin filaments were also found to be toxic to p53-deficient tumors. In p53
      deficient cells, PTX-2 triggers apoptosis through mitochondrial dysfunction, and
      this is followed by the release of proapoptotic factors and caspase activation.
      Furthermore, we observed Bax activation and Bim induction only in p53-deficient
      cells after PTX-2 treatment. RNA interference of either Bim or Bax resulted in
      the inhibition of caspases and apoptosis induced by PTX-2. However, the small
      interfering RNAs (SiRNA) of Bim blocked a conformational change of Bax, but Bax
      SiRNA did not affect Bim expression. Therefore, these results suggest that Bim
      triggers apoptosis by activating Bax in p53-deficient tumors upon actin damage,
      and that actin inhibitors may be potent chemotherapeutic agents against p53
      deficient tumors.

PMID- 15870702
TI  - Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death
      through mitotic catastrophe accompanied by senescence-like phenotype.
AB  - Chronic exposure of many human hepatoma cell lines to a low dose (LD) of
      doxorubicin induced a senescence-like phenotype (SLP) accompanied by enlargement
      of cells and increased senescence-associated beta-galactosidase activity. LD
      doxorubicin-induced SLP was preceded by multinucleation and downregulation of
      multiple proteins with mitotic checkpoint function, including CENP-A, Mad2,
      BubR1, and Chk1. LD doxorubicin-treated cells eventually underwent cell death
      through mitotic catastrophe. When we investigated whether LD doxorubicin-induced
      cell death shares biochemical characteristics with high dose (HD) doxorubicin
      induced apoptosis in Huh-7 cells, we observed that externalization of
      phosphatidyl serine and release of mitochondrial cytochrome c into the cytosol
      was associated with both types of cell death. However, propidium iodide exclusion
      assays showed that membrane integrity was lost in the initial phase of LD
      doxorubicin-induced cell death through mitotic catastrophe, whereas it was lost
      during the late phase of HD doxorubicin-induced apoptosis. Furthermore, HD
      doxorubicin-induced apoptosis but not LD doxorubicin-induced mitotic catastrophe
      led to transient activation of NF-kappaB and strong, sustained activations of
      p38, c-Jun N-terminal kinase, and caspases. Collectively, these results indicate
      that different doses of doxorubicin activate different regulatory mechanisms to
      induce either apoptosis or cell death through mitotic catastrophe.

PMID- 15870703
TI  - Inactivation of the tissue inhibitor of metalloproteinases-2 gene by promoter
      hypermethylation in lymphoid malignancies.
AB  - The tissue inhibitor of metalloproteinases-2 (TIMP-2) is known to antagonize
      matrix metalloproteinase activity and to suppress tumor growth, angiogenesis,
      invasion and metastasis. We analysed the methylation status of the CpG island in
      the TIMP-2 promoter region by methylation-specific polymerase chain reaction
      (MSP) in hematopoietic cell lines. TIMP-2 promoter hypermethylation in the
      lymphoma cell line Raji and the leukemia cell line KG1a was associated with
      transcriptional repression. Treatment with the demethylating agent 5-aza-2'
      deoxycytidine resulted in TIMP-2 upregulation in both cell lines. TIMP-2 was
      expressed in the cell lines HL60, U266 and XG1, which carry an unmethylated
      promoter region. MSP analysis of primary patient samples revealed aberrant
      methylation of TIMP-2 in 33/90 (36.7%) cases of non-Hodgkin's lymphoma (NHL), but
      not in normal peripheral blood lymphocytes as well as in nonmalignant bone marrow
      and lymph nodes. The frequency of TIMP-2 methylation was slightly higher in
      aggressive NHL subtypes compared to those with an indolent subtype (38.6 versus
      33.3%). In contrast, TIMP-2 was not hypermethylated in any of the 40 cases of
      acute myelogenous leukemia examined. We conclude that promoter hypermethylation
      of TIMP-2 is a novel epigenetic event in the pathogenesis of lymphoid
      malignancies and may contribute to a more aggressive NHL phenotype.

PMID- 15870704
TI  - Opposite effects of estrogen receptors alpha and beta on MCF-7 sensitivity to the
      cytotoxic action of TNF and p53 activity.
AB  - We have investigated the effect of estrogen on p53 cellular location and its
      influence on tumor cell susceptibility to tumor necrosis factor (TNF)-mediated
      cytotoxic action. For this purpose, we have used the TNF-sensitive human breast
      adenocarcinoma MCF-7 and its derivative, the TNF-resistant 1001 clone. Our data
      indicate that although estrogen receptor (ER)alpha is present in both cell lines,
      estrogen treatment (1x10(-8) M) has an influence only on the MCF-7 cells and
      protects these cells from the TNF cytotoxicity. This protective effect is
      associated with translocation of p53 from the nucleus to the cytoplasm in p53
      wild-type MCF-7 and not in p53-mutated 1001 cells. The translocation of p53 in
      MCF-7 cells results in a decrease in its transcriptional activity, as revealed by
      diminished p21(WAF1/CIP1) induction and an altered ratio of Bax and Bcl-2
      proteins. The estrogen-induced effects are reversed by the selective estrogen
      inhibitor 182, 780 (1x10(-6) M). Interestingly, transient transfection of MCF-7
      cells with ERbeta but not ERalpha cDNA encoding plasmid results in retention of
      p53 in the nucleus, a subsequent potentiation of its transcriptional activity,
      and in an increased MCF-7 sensitivity to TNF. The estrogen effects on p53
      location and transcriptional activity may involve the mdm2 protein since both
      events were reversed following MCF-7 transfection with plasmid encoding the ARF
      cDNA. These studies suggest that estrogen-induced MCF-7 cell survival in the
      presence of TNF requires a transcriptionally active p53 and, more importantly,
      indicate that introduction of ERbeta can attenuate the estrogen effects on the
      p53 protein location, its transcriptional activity and also results in a
      potentiation of cell sensitivity to TNF-mediated cell death.

PMID- 15870705
TI  - A germ line mutation that delays prostate cancer progression and prolongs
      survival in a murine prostate cancer model.
AB  - Circulating insulin-like growth factor-I (IGF-I) levels have been shown to be
      related to risk of prostate cancer in epidemiologic studies. While specific
      genetic loci responsible for interindividual variation in circulating IGF-I
      levels in normal men have not been identified, candidate genes include those
      involved in the growth hormone (GH)-IGF-I axis such as the hypothalamic factors
      GH releasing hormone (GHRH) and somatostatin and their receptors. To investigate
      the role of the GH-IGF-I axis on in vivo prostate carcinogenesis and neoplastic
      progression, we generated mice genetically predisposed to prostate cancer (the
      TRAMP model) to be homozygous for lit, a mutation that inactivates the GHRH
      receptor (GHRH-R) and reduces circulating levels of GH and IGF-I. The lit
      mutation significantly reduced the percentage of the prostate gland showing
      neoplastic changes at 35 weeks of age (P=0.0005) and was also associated with
      improved survival (P<0.01). These data provide an example of a germ line mutation
      that reduces risk in an experimental prostate carcinogenesis model. The results
      suggest that prostate carcinogenesis and progression may be influenced by germ
      line variation of genes encoding signalling molecules in the GH-IGF-I axis.

PMID- 15870706
TI  - Epigenetic mechanisms affect mutant p53 transgene expression in WAP-mutp53
      transgenic mice.
AB  - We describe the construction and phenotypic characterization of 23 whey acidic
      protein (WAP)-mutp53 transgenic mouse lines. The mutp53-expressing lines showed a
      mosaic expression pattern for the transgenes, leading to a heterogeneous yet
      mouse line-specific expression pattern for mutp53 upon induction. Only few lines
      were obtained, in which the majority of the induced mammary epithelial cells
      expressed the mutp53 transgene, most of the transgenic lines did not express
      mutp53, or expressed the transgene in less than 2% of the induced mammary
      epithelial cells. Hormone requirements for mutp53 transgene expression from the
      WAP-promoter differed in high and low expressing lines, being low in high
      expressing lines, and even lower in multiparous mutp53 mice, where persistent
      expression of the transgene occurred. Repeated induction of mutp53 expression
      through repeated parturition resulted in the formation of expanding mutp53
      expressing foci within the mammary alveolar epithelium. The data suggest that
      epigenetic mechanisms play a role in modulating the expression of the mutp53
      transgene. To support this idea, we crossed a nonexpressing WAP-mutp53 line with
      a strongly SV40 T-antigen-expressing WAP-T mouse line. In the bitransgenic mice,
      T-antigen-induced chromatin remodeling led to re-expression of epigenetically
      silenced mutp53 transgene(s). In these mice, mutp53 expression was much more
      variable compared to SV40 T-antigen expression, and seemed to depend on the
      coexpression of SV40 T-antigen. Mutp53 expression in this system thus resembles
      the situation in many human tumors, where one can observe a heterogeneous
      expression of mutp53, despite a homogeneous distribution of the p53 mutation in
      the tumor cells.

PMID- 15870707
TI  - Assessment of a fragment of e-cadherin as a serum biomarker with predictive value
      for prostate cancer.
AB  - In prostate cancer, biomarkers may provide additional value above standard
      clinical and pathology parameters to predict outcome after specific therapy. The
      purpose of this study is to evaluate an 80 kDa fragment of the cell adhesion
      molecule e-cadherin as a serum biomarker. A broad spectrum of prostate cancer
      serum samples, representing different stages of prostate cancer disease,
      including benign prostatic hyperplasia (BPH), localised (Loc PCA) and metastatic
      prostate cancer (Met PCA), was examined for the cleaved product. There is a
      significant difference in the expression level of the 80 kDa fragment in the
      serum of healthy individuals vs patients with BPH and between BPH vs Loc PCA and
      Met PCA (P<0.001). Highest expression levels are observed in advanced metastatic
      disease. In the cohort of Loc PCA cases, there was no association between the 80
      kDa serum concentration and clinical parameters. Interestingly, patients with an
      80 kDa level of >7.9 microg l(-1) at the time of diagnosis have a 55-fold higher
      risk of biochemical failure after surgery compared to those with lower levels.
      This is the first report of the application of an 80 kDa fragment of e-cadherin
      as a serum biomarker in a broad spectrum of prostate cancer cases. At an
      optimised cutoff, high expression at the time of diagnosis is associated with a
      significantly increased risk of biochemical failure, potentially supporting its
      use for a tailored follow-up protocol for those patients.

PMID- 15870708
TI  - The Akt inhibitor KP372-1 suppresses Akt activity and cell proliferation and
      induces apoptosis in thyroid cancer cells.
AB  - The phosphatidylinositol 3' kinase (PI3K)/phosphatase and tensin homologue
      deleted on chromosome ten/Akt pathway, which is a critical regulator of cell
      proliferation and survival, is mutated or activated in a wide variety of cancers.
      Akt appears to be a key central node in this pathway and thus is an attractive
      target for targeted molecular therapy. We demonstrated that Akt is highly
      phosphorylated in thyroid cancer cell lines and human thyroid cancer specimens,
      and hypothesised that KP372-1, an Akt inhibitor, would block signalling through
      the PI3K pathway and inhibit cell proliferation while inducing apoptosis of
      thyroid cancer cells. KP372-1 blocked signalling downstream of Akt in thyroid
      tumour cells, leading to inhibition of cell proliferation and increased
      apoptosis. As thyroid cancer consistently expresses phosphorylated Akt and KP372
      1 effectively blocks Akt signalling, further preclinical evaluation of this
      compound for treatment of thyroid cancer is warranted.

PMID- 15870709
TI  - Aberrant expression of RAB1A in human tongue cancer.
AB  - This study was designed to identify specific gene expression changes in tongue
      squamous cell carcinomas (TSCCs) compared with normal tissues using in-house cDNA
      microarray that comprised of 2304 full-length cDNAs from a cDNA library prepared
      from normal oral tissues, primary oral cancers, and oral cancer cell lines. The
      genes identified by our microarray system were further analysed at the mRNA or
      protein expression level in a series of clinical samples by real-time
      quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis
      and imuunohositochemistry. The microarray analysis identified a total of 16 genes
      that were significantly upregulated in common among four TSCC specimens.
      Consistent with the results of the microarray, increased mRNA levels of selected
      genes with known molecular functions were found in the four TSCCs. Among genes
      identified, Rab1a, a member of the Ras oncogene family, was further analysed for
      its protein expression in 54 TSCCs and 13 premalignant lesions. We found a high
      prevalence of Rab1A-overexpression not only in TSCCs (98%) but also in
      premalignant lesions (93%). Thus, our results suggest that rapid characterisation
      of the target gene(s) for TSCCs can be accomplished using our in-house cDNA
      microarray analysis combined with the qRT-PCR and immunohistochemistry, and that
      the Rab1A is a potential biomarker of tongue carcinogenesis.

PMID- 15870710
TI  - Co-expression of RON and MET is a prognostic indicator for patients with
      transitional-cell carcinoma of the bladder.
AB  - Recepteur d'Origine Nantais (RON) is a distinct receptor tyrosine kinase in the c
      met proto-oncogene family. We examined the mutational and expression patterns of
      RON in eight human uroepithelial cell lines. Biological effects of RON
      overexpression on cancer cells were investigated in vitro, and the prognostic
      significance of RON and/or c-met protein (MET) expression was analysed in a
      bladder cancer cohort (n=183). There was no evidence of mutation in the kinase
      domain of RON. Overexpression of RON using an inducible Tet-off system induced
      increased cell proliferation, motility, and antiapoptosis. Immunohistochemical
      analysis showed that RON was overexpressed in 60 cases (32.8%) of primary
      tumours, with 14 (23.3%) showing a high level of expression. Recepteur d'Origine
      Nantais expression was positively associated with histological grading, larger
      size, nonpapillary contour, and tumour stage (all P<0.01). In addition, MET was
      overexpressed in 82 cases (44.8%). Co-expressed RON and MET was significantly
      associated with decreased overall survival (P=0.005) or metastasis-free survival
      (P=0.01) in 35 cases (19.1%). Recepteur d'Origine Nantais-associated signalling
      may play an important role in the progression of human bladder cancer. Evaluation
      of RON and MET expression status may identify a subset of bladder-cancer patients
      who require more intensive treatment.

PMID- 15870712
TI  - A prospective longitudinal study of performance status, an inflammation-based
      score (GPS) and survival in patients with inoperable non-small-cell lung cancer.
AB  - The value of an inflammation-based prognostic score (Glasgow Prognostic score,
      GPS) was compared with performance status (ECOG-ps) in a longitudinal study of
      patients (n=101) with inoperable non-small-cell lung cancer (NSCLC). At
      diagnosis, stratified for treatment, only the GPS (HR 2.32, 95% CI 1.52-3.54,
      P<0.001) was a significant predictor of survival. In contrast, neither the GPS
      nor ECOG-ps measured at 3-6 months follow-up were significant predictors of
      residual survival. This study confirms the prognostic value of the GPS, at
      diagnosis, in patients with inoperable NSCLC. However, the role of the GPS and
      ECOG-ps during follow-up has not been established.

PMID- 15870711
TI  - Imatinib mesylate (Gleevec) downregulates telomerase activity and inhibits
      proliferation in telomerase-expressing cell lines.
AB  - Imatinib mesylate (IM) is a tyrosine kinase inhibitor, which inhibits
      phosphorylation of downstream proteins involved in BCR-ABL signal transduction.
      It has proved beneficial in treating patients with chronic myeloid leukaemia
      (CML). In addition, IM demonstrates activity against malignant cells expressing c
      kit and platelet-derived growth factor receptor (PDGF-R). The activity of IM in
      the blastic crisis of CML and against various myeloma cell lines suggests that
      this drug may also target other cellular components. In the light of the
      important role of telomerase in malignant transformation, we evaluated the effect
      of IM on telomerase activity (TA) and regulation in various malignant cell lines.
      Imatinib mesylate caused a dose-dependent inhibition of TA (up to 90% at a
      concentration of 15 microM IM) in c-kit-expressing SK-N-MC (Ewing sarcoma), SK
      MEL-28 (melanoma), RPMI 8226 (myeloma), MCF-7 (breast cancer) and HSC 536/N
      (Fanconi anaemia) cells as well as in ba/F3 (murine pro-B cells), which do not
      express c-kit, BCR-ABL or PDGF-R. Imatinib mesylate did not affect the activity
      of other DNA polymerases. Inhibition of TA was associated with 50% inhibition of
      proliferation. The inhibition of proliferation was associated with a decrease in
      the S-phase of the cell cycle and an accumulation of cells in the G2/M phase. No
      apoptosis was observed. Inhibition of TA was caused mainly by post-translational
      modifications: dephosphorylation of AKT and, to a smaller extent, by early
      downregulation of hTERT (the catalytic subunit of the enzyme) transcription.
      Other steps of telomerase regulation were not affected by IM. This study
      demonstrates an additional cellular target of IM, not necessarily mediated via
      known tyrosine kinases, that causes inhibition of TA and cell proliferation.

PMID- 15870714
TI  - Delays in the diagnosis of six cancers: analysis of data from the National Survey
      of NHS Patients: Cancer.
AB  - The aim of this paper is to describe and compare components of diagnostic delay
      (patient, primary care, referral, secondary care) for six cancers (breast,
      colorectal, lung, ovarian, prostate and non-Hodgkin's lymphoma), and to compare
      delays in patients who saw their GP prior to diagnosis with those who did not.
      Secondary data analysis of The National Survey of NHS Patients: Cancer was
      undertaken (65 192 patients). Breast cancer patients experienced the shortest
      total delays (mean 55.2 days), followed by lung (88.5), ovarian (90.3), non
      Hodgkin's lymphoma (102.8), colorectal (125.7) and prostate (148.5). Trends were
      similar for all components of delay. Compared with patient and primary care
      delays, referral delays and secondary care delays were much shorter. Patients who
      saw their GP prior to diagnosis experienced considerably longer total diagnostic
      delays than those who did not. There were significant differences in all
      components of delay between the six cancers. Reducing diagnostic delays with the
      intention of increasing the proportion of early stage cancers may improve cancer
      survival in the UK, which is poorer than most other European countries.
      Interventions aimed at reducing patient and primary care delays need to be
      developed and their effect on diagnostic stage and psychological distress
      evaluated.

PMID- 15870713
TI  - Survival rate in patients with hepatocellular carcinoma: a retrospective analysis
      of 389 patients.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide.
      However, treatment options are limited and often inefficient. The aim of this
      study was to determine current survival rates for patients diagnosed with HCC and
      to identify prognostic factors, which will help in choosing optimal therapies for
      individual patients. A retrospective analysis of medical records was performed on
      389 patients who were identified through the central tumour registry at our
      institution from 1998 to 2003. Clinical parameters, treatments received and
      survival curves from time of diagnosis were analysed. Overall median survival was
      11 months. Liver cirrhosis was diagnosed in 80.5% of all patients. A total of 170
      patients received transarterial chemoembolisation (TACE) and/or percutaneous
      ethanol injections (PEI) with a median survival rate of 16 months for patients
      receiving TACE, 11 months for patients receiving PEI and 24 months for patients
      receiving TACE followed by PEI. Independent negative prognostic parameters for
      survival were the presence of portal vein thrombosis, advanced liver cirrhosis
      (Child-Pugh score B or C) and a score of >2. This study will help to estimate
      survival rates for patients with HCC according to their clinical status at
      diagnosis and the treatments received.

PMID- 15870715
TI  - Gefitinib treatment affects androgen levels in non-small-cell lung cancer
      patients.
AB  - Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR,
      HER1/ErbB1) tyrosine kinase, has been shown to have clinical activity against non
      small-cell lung cancers (NSCLCs), especially in women nonsmokers with
      adenocarcinomas. The aim of the present study was to clarify the relationship
      between androgen levels and gefitinib treatment in patients with advanced NSCLCs.
      Sera from 67 cases (36 men and 31 women) were obtained pretreatment and during
      treatment with gefitinib monotherapy (days 14-18) for examination of
      testosterone, dehydroepiandrosterone sulphate (DHEA), and dehydroepiandrosterone
      sulphate (DHEAS) levels. Testosterone and DHEA during treatment were
      significantly lower than the pretreatment values in both women and men, and the
      DHEAS levels during treatment were also significantly lowered in women. Gefitinib
      treatment significantly suppressed androgen levels, especially in women who had
      no smoking history. In addition, hormone levels in women responding to gefitinib
      were significantly lower during the treatment than in women who did not respond.
      Gefitinib-associated decrease in serum androgen levels may play a role in its
      clinical efficacy.

PMID- 15870716
TI  - Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7
      days off in patients with advanced, refractory solid tumours.
AB  - BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth
      factor receptor (VEGFR) inhibitor that targets tumour cell proliferation and
      tumour angiogenesis. This Phase I study was undertaken to determine the safety
      profile, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs),
      pharmacokinetics, and tumour response profile of oral BAY 43-9006 in patients
      with advanced, refractory solid tumours. BAY 43-9006 was administered daily for
      repeated cycles of 21 days on/7 days off. A total of 44 patients were enrolled at
      doses from 50 to 800 mg b.i.d. Pharmacokinetic profiles of BAY 43-9006 in plasma
      were determined during the first treatment cycle. The most frequently reported
      adverse events over multiple cycles were gastrointestinal (75%), dermatologic
      (71%), constitutional (68%), pain (64%), or hepatic (61%) related. A MTD of 400
      mg b.i.d. BAY 43-9006 was defined. BAY 43-9006 was absorbed rapidly; steady-state
      conditions were reached within 7 days. BAY 43-9006 exposure increased
      nonproportionally with increasing dose. In all, 32 patients were evaluated for
      tumour response: 15 patients showed tumour progression, 16 patients experienced
      stable disease (>6 months in eight patients), and one patient with renal cell
      carcinoma achieved a partial response. BAY 43-9006 given for 21 days with 7 days
      off treatment was safe, well tolerated, and showed antitumour activity.

PMID- 15870717
TI  - The use of radiofrequency in cancer.
AB  - Radiofrequency ablation (RFA) provides an effective technique for minimally
      invasive tissue destruction. An alternating current delivered via a needle
      electrode causes localised ionic agitation and frictional heating of the tissue
      around the needle. Image-guided, percutaneous ablation techniques have been
      developed in most parts of the body, but the most widely accepted applications
      are for the treatment of hepatocellular carcinoma (HCC) in early cirrhosis,
      limited but inoperable colorectal liver metastases, inoperable renal cell
      carcinoma and inoperable primary or secondary lung tumours. The procedures are
      well tolerated and the complication rates low. Patients with coexistent morbidity
      who are not suitable for surgery are often able to undergo RFA. Most treatments
      in the lung, kidney and for HCC are performed under conscious sedation with an
      overnight hospital stay or as a day-case. Larger more complicated ablations, for
      example, in hepatic metastases may require general anaesthesia. Limitations of
      RFA include the volume of tissue that can be ablated in a timely fashion, that
      is, most centres will treat 3-5 tumours up to 4-5 cms in diameter. Early series
      reporting technical success and complications are available for lung and renal
      ablation. Liver ablation is better established and 5-year survival figures are
      available from several centres. In patients with limited but inoperable
      colorectal metastases, the 5-year survival ranges from 26 to 30% and for HCC it
      is just under 50%. In summary, RFA provides the opportunity for localised tissue
      destruction of limited volumes of tumour; it can be offered to nonsurgical
      candidates and used in conjunction with systemic therapy.

PMID- 15870718
TI  - Salvage chemotherapy with irinotecan, 5-fluorouracil and leucovorin for taxane-
      and cisplatin-refractory, metastatic gastric cancer.
AB  - We performed a phase II study of combination chemotherapy with irinotecan, 5
      fluorouracil (5-FU) and leucovorin in metastatic gastric cancer patients who were
      previously treated with taxane and cisplatin, to evaluate the antitumour activity
      and toxicity of the combination chemotherapy. The metastatic gastric
      adenocarcinoma patients who were previously treated with taxane and cisplatin
      combination as first line, and had at least one measurable lesion, 0-2 ECOG
      performance status and adequate organ functions, were considered eligible. They
      received irinotecan (150 mg m(-2), day 1) and leucovorin (100 mg m(-2), day 1),
      followed by continuous infusion of 5-FU (1000 mg m(-2) day(-1), days 1 and 2)
      every 2 weeks. Treatment was continued until progression of disease was observed.
      In all, 64 patients were treated with this combination chemotherapy. The median
      age of the patients was 55 years (range, 33-74 years), and the median ECOG
      performance status was 1 (0-1, 61 (95%)). Out of 64 patients, 57 were assessable
      for response. Among 57 assessable patients, no complete response and 12 partial
      responses were observed (overall response rate, 21%; 95% confidence interval
      (CI), 10-32%). Stable disease was observed in 14 patients (25%) and progressive
      disease in 31 patients (54%). The median time to progression was 2.5 months (95%
      CI, 1.6-3.4) and the median overall survival since the start of the second-line
      modified FOLFIRI was 7.6 months (95% CI, 6.5-8.7). Grade 3-4 haematologic
      toxicities included neutropenia in seven patients (11%) and thrombocytopenia in
      five patients (8%). Grade 3-4 nonhaematologic toxicities included diarrhoea in
      two patients (3%) and vomiting in two patients (3%). There were no treatment
      related deaths. The combination of irinotecan, 5-FU and leucovorin showed
      moderate activity and favourable toxicity profile as a second-line treatment in
      metastatic gastric cancer patients, who were previously treated with taxane and
      cisplatin.

PMID- 15870719
TI  - A phase II trial of gefitinib with 5-fluorouracil, leucovorin, and irinotecan in
      patients with colorectal cancer.
AB  - Inhibition of epidermal growth factor receptor (EGFR) signalling contributes to
      the therapy of colorectal cancer. Gefitinib, an oral EGFR tyrosine kinase
      inhibitor, shows supra-additive growth inhibition with irinotecan and
      fluoropyrimidines in xenograft models. We designed a study to determine the
      tolerability and efficacy of gefitinib in combination with irinotecan, infusional
      5-fluorouracil (5-FU) and leucovorin (LV), on a 2-week schedule. Among 13
      patients with advanced colorectal cancer, 10 required dose reductions of
      irinotecan and 5-FU because of dehydration, diarrhoea, and neutropenia, seven of
      whom required hospitalisation, three with neutropenic fever. One patient achieved
      partial response and seven had disease stabilisation. The combination of this
      standard chemotherapy regimen with gefitinib is associated with excessive
      toxicity, suggesting an interaction at a pharmacokinetic or pharmacodynamic
      level.

PMID- 15870720
TI  - Inflammation-associated gene expression is altered between normal human ovarian
      surface epithelial cells and cell lines derived from ovarian adenocarcinomas.
AB  - Ovulation is believed to contribute to the development of ovarian cancers that
      derive from the ovarian surface epithelium (OSE). The process of ovulation is
      synonymous with inflammation and inflammatory cytokines such as interleukin
      1alpha (IL-1alpha) have recently been shown to induce both inflammatory and anti
      inflammatory responses in human OSE (HOSE) cells. In this study we directly
      compared levels of IL-1alpha-induced gene expression by analysing the levels of
      11beta-hydroxysteroid dehydrogenase (11betaHSD) types 1 (11betaHSD-1) and 2
      (11betaHSD-2), cyclooxygenase-2 (COX-2), IL-1 receptor (IL-1R) and glucocorticoid
      receptor alpha (GRalpha) mRNA between normal HOSE cells and cell lines derived
      from poorly differentiated (SKOV-3, BG-1, PEO-4) and well-differentiated (PEO-14)
      ovarian adenocarcinoma. In HOSE cell cultures, and to a lesser extent PEO-14
      cells, the basal mRNA levels of COX-2 and 11betaHSD-1 were relatively high and
      further shown to be induced in response to IL-1alpha (for HOSE cells; >20-fold,
      P<0.05 and PEO-14 cells; >3fold, P<0.05). However, whereas HOSE cells expressed a
      low level of 11betaHSD-2 mRNA that was only mildly responsive to IL-1alpha (1.3
      fold, P<0.001), all cell lines exhibited a higher basal level of 11betaHSD-2 mRNA
      that was in some cases further stimulated in PEO-4 cells (five-fold; P<0.05) or
      suppressed in SKOV-3 cells (two-fold; P<0.01) in response to IL-1alpha. All cells
      tested expressed IL-1R and, with the exception of BG-1, GRalpha. These results
      indicate that cell lines derived from ovarian cancers have lost the ability to
      respond normally to inflammatory cytokines such as IL-1alpha. The finding that
      normal OSE cells, in contrast to cell lines derived from patients with ovarian
      adenocarcinoma, abundantly express 11betaHSD-1 mRNA but are essentially devoid of
      11betaHSD-2 mRNA supports the concept that the pattern of 11betaHSD isoform gene
      expression is a defining feature of neoplastic cellular transformation, which
      might have particular relevance to the ovary.

PMID- 15870722
TI  - Science or science fiction?

PMID- 15870723
TI  - Searching for the silver lining.

PMID- 15870721
TI  - Zoledronic acid significantly improves pain scores and quality of life in breast
      cancer patients with bone metastases: a randomised, crossover study of community
      vs hospital bisphosphonate administration.
AB  - Patients with bone metastases from breast cancer often experience substantial
      skeletal complications -- including debilitating bone pain -- which negatively
      affect quality of life. Zoledronic acid (4 mg) has been demonstrated to reduce
      significantly the risk of skeletal complications in these patients and is
      administered via a short, 15-min infusion every 3 weeks, allowing the possibility
      for home administration. This study compared the efficacy and safety of
      zoledronic acid administered in the community setting vs the hospital setting in
      breast cancer patients with > or =1 bone metastasis receiving hormonal therapy.
      After a lead-in phase of three infusions of 4 mg zoledronic acid in the hospital
      setting, 101 patients were randomized to receive three open-label infusions in
      the community or hospital setting, followed by three infusions in the opposite
      venue (a total of nine infusions). The Brief Pain Inventory (BPI) and the
      European Organisation for Research and Treatment of Cancer Quality of Life Core
      Questionnaire 30 (EORTC QLQ-C30) were used to assess potential benefits of
      zoledronic acid therapy. At study end, analysis of the BPI showed significant
      reductions in worst pain (P=0.008) and average pain in the last 7 days (P=0.039),
      and interference with general activity (P=0.012). In each case, there were
      significantly greater improvements in pain scores after treatment in the
      community setting compared with the hospital crossover setting for worst pain
      (P=0.021), average pain (P=0.003), and interference with general activity
      (P=0.001). Overall global health status showed a significant median improvement
      of 8.3% (P=0.013) at study end. Physical, emotional, and social functioning also
      showed significant overall improvement (P=0.013, 0.005, and 0.043, respectively).
      Furthermore, physical, role, and social functioning showed significantly greater
      improvements after treatment in the community setting compared with the hospital
      crossover setting (P=0.018, 0.001, and 0.026, respectively). There was no
      difference between hospital and community administration in renal or other
      toxicity, with zoledronic acid being well tolerated in both treatment settings.
      These data confirm the safety and quality-of-life benefits of zoledronic acid in
      breast cancer patients with bone metastases, particularly when administered in
      the community setting.

PMID- 15870724
TI  - Spindly clathrin.

PMID- 15870725
TI  - Prepore for a breakthrough.

PMID- 15870726
TI  - An Achilles' heel for breast cancer?

PMID- 15870727
TI  - Knowing when not to stop.

PMID- 15870728
TI  - Hitting transcription in all the right places.

PMID- 15870729
TI  - Rad50 connects by hook or by crook.

PMID- 15870731
TI  - Ribozyme catalysis: not different, just worse.
AB  - Evolution has resoundingly favored protein enzymes over RNA-based catalysts, yet
      ribozymes occupy important niches in modern cell biology that include the
      starring role in catalysis of protein synthesis on the ribosome. Recent results
      from structural and biochemical studies show that natural ribozymes use an
      impressive range of catalytic mechanisms, beyond metalloenzyme chemistry and
      analogous to more chemically diverse protein enzymes. These findings make it
      increasingly possible to compare details of RNA- and protein-based catalysis.

PMID- 15870732
TI  - Benevolence and personal tsunamis.

PMID- 15870733
TI  - Overseas dentists.

PMID- 15870742
TI  - Does your practice website need updating?
AB  - The internet is becoming a more and more powerful tool and many dental
      practitioners use it to advertise their dental service; some dental practices
      even offer on-line appointment booking! It is not unreasonable to surmise that
      use of the internet is likely to become increasingly common practice by dentists
      in the future. This is not surprising as the World Wide Web (WWW) provides an
      opportunity for dentists to advertise themselves and their practices to a wide
      audience in a relatively economical manner.

PMID- 15870743
TI  - Tonsillolith as a halitosis-inducing factor.
AB  - Halitosis, or bad breath, is a common concern for many people. The main causes
      are known to be periodontal disease and tongue coating. We present a case of an
      incidental tonsillolith occurrence, which was a halitosis-inducing factor. Our
      results show that tonsilloliths should be considered as a possible cause of
      halitosis.

PMID- 15870744
TI  - Bifid tongue - a complication of tongue piercing.
AB  - Tongue piercing is associated with significant morbidity. We report on a patient
      with a bifid tongue defect following insertion of a tongue ornament. This
      abnormality resulted in severe emotional disturbance.

PMID- 15870745
TI  - The neutral zone impression revisited.
AB  - The neutral zone technique is an alternative approach for the construction of
      lower complete dentures. It is most effective for dentures where there is a
      highly atrophic ridge and a history of denture instability. The technique aims to
      construct a denture that is shaped by muscle function and is in harmony with the
      surrounding oral structures. The technique is by no means new but is a valuable
      one. This paper aims to provide clinicians with the knowledge to use the
      technique - a list of competencies is included.

PMID- 15870746
TI  - Reasons for tooth extraction in four general dental practices in South Wales.
AB  - Tooth retention has been one of the main aims of oral care which in turn could
      have contributed to the social oral health divide. To investigate this issue
      further, data collected for a group audit was used to study the reasons for tooth
      extraction for patients attending for routine treatment at four dental practices.
      The practices served populations in areas with different levels of deprivation in
      South Wales. In 558 teeth extracted over 417 visits, the reasons for extractions
      were: caries 59%, periodontal disease 29.1%, pre-prosthetic 1%, wisdom teeth
      4.6%, orthodontic 5.5%, trauma 1.2%, patient request 2.4% and 6.2% other reason.
      The number of extraction visits per day within the group of dental surgeons
      varied with three practitioners performing more than three extraction visits per
      day while one practitioner had only 0.51. These reasons did not significantly
      depend on levels of deprivation. However, significantly more teeth were extracted
      for caries in the most deprived group in comparison to the least deprived.
      Therefore, could there be a case for appropriate extractions in the quest for
      equitable care?

PMID- 15870753
TI  - Conducting trials.

PMID- 15870754
TI  - Toothwear and erosion.

PMID- 15870755
TI  - The effect of bleaching on enamel susceptibility to acid erosion and
      demineralisation.
AB  - INTRODUCTION: The purpose of this in vitro study was to determine if enamel that
      had been bleached by carbamide (urea) peroxide gel (CPG) was at increased risk of
      either acid erosion or demineralisation (early caries) than un-bleached enamel.
      METHODS: Human incisors were employed. The samples were randomly assigned to one
      of 4 groups; a) 10% CPG, b) 16% CPG, c) 22% CPG and d) 10% CPG with xylitol,
      fluoride and potassium. Each specimen was moistened with saliva and the
      appropriate formulation placed for 2 hours for a total of 40 hours of exposure.
      In order to ensure that bleaching had taken place, tooth shades were monitored
      using the Shade-Eye device. Following the bleaching process, one half of the
      specimen was subjected to an erosive challenge, the other to a demineralisation
      system with one half of each sub-sample retained as a non-bleached control.
      Samples were assessed longitudinally with quantitative light-induced fluorescence
      (QLF) and at the conclusion of the study with transverse micro-radiography (TMR).
      RESULTS: Erosion was detected in all samples (DeltaQ 126+/-23.4), in both
      bleached and non-bleached areas. There was no statistical difference between the
      bleached and non-bleached areas either within the treatment groups or between
      them. Caries-like lesions were detected on all samples; TMR revealed sub-surface
      lesions on all teeth and QLF data supported this (DeltaQ 89+/-18.9). Following
      statistical analysis there were no differences detected between the bleached and
      non-bleached areas, nor between the different concentrations of the bleaching
      solution. CONCLUSION: These results suggest that tooth bleaching with carbamide
      (urea) peroxide (using commercially available concentrations) does not increase
      the susceptibility of enamel to acid erosion or caries.

PMID- 15870756
TI  - Management of dental trauma in primary care: a postal survey of general dental
      practitioners.
AB  - OBJECTIVES: To determine the self-perceived knowledge and attitudes of general
      dental practitioners (GDPs) concerning management of dental trauma in primary
      care. To identify potential barriers to the management of dental trauma in
      primary care. DESIGN AND SETTING: A self-completion postal questionnaire survey
      of 417 GDPs in six local health authority districts in northeast England. MAIN
      OUTCOME MEASURES: Likert scale responses to 20 statements designed to test self
      perceived knowledge and attitudes. Following descriptive statistical analysis.
      Factor analysis with principle components analysis was undertaken to identify
      areas of correlation in questionnaire responses, followed by Chi squared test,
      Spearman's Rank Correlation and analysis of variance (ANOVA) to measure
      association between variables. RESULTS: The response rate was 74%. Enamel and
      dentine fractures were the most common injury, with 45% of GDPs responding seeing
      more than 10 cases of dental trauma in the preceding year and 53% of respondents
      seeing one to three cases of complicated crown fracture. Seventy-eight per cent
      believed that NHS remuneration was inadequate, but only 8% would refer patients
      with dental trauma to secondary care for this reason. Half of the GDPs believed
      that trauma could be treated more effectively in practice if NHS payments were
      greater. GDPs were significantly more likely to agree with this statement if they
      had previously undertaken a postgraduate course in the treatment of dental trauma
      (p=0.002). Single handed GDPs were statistically significantly more likely to
      agree with the statements 'I would not treat dental trauma cases at my practice
      because the NHS payment is inadequate' (p=0.008) and 'Treating dental trauma at
      my practice requires too much of my clinical time to be worthwhile' (p=0.002).
      Ninety-six per cent of GDPs disagreed that treatment of dental trauma rested
      solely within secondary care. Ninety-six per cent of GDPs agreed that they had a
      responsibility to provide initial emergency treatment for trauma patients prior
      to referral. Eighty-eight per cent of GDPs felt that aids to management would be
      useful. CONCLUSIONS: Although GDPs believed that financial remuneration was
      inadequate, this did not prevent them treating trauma cases. They strongly agreed
      that they had responsibility for the management of dental trauma in primary care
      and that they believed trauma could be treated more effectively in practice if
      payment was greater. Time constraints were perceived as a barrier to long-term
      management of complex trauma cases in primary care. GDPs would welcome the use of
      management aids.

PMID- 15870757
TI  - Science and technology in Turner's Georgian dentist's rooms.
AB  - Turner's painting of a dental surgeon's rooms, discussed in the first of these
      two papers,(1) is a very satisfying work of art, successful in its relaying of a
      domestic drama, and also fulfilling Payne Knight's commission to produce a work
      to equal that of the older masters. It cannot, though, be relied upon to show us
      what a late Georgian dentist's rooms actually looked like. For this we are very
      fortunate to have Turner's sketchbook, with its preparatory drawings for the
      painting.

PMID- 15870773
TI  - Oral health assessment in clinical practice: new perspectives on the need for a
      comprehensive and evidence based approach.
AB  - This paper highlights one aspect of a presentation to be given at the BDA
      Conference and is written in the context of dentistry in primary care. Careful
      oral health assessment as a foundation to good treatment planning and quality
      dentistry is not new, but there are a number of important new perspectives
      emerging across countries and healthcare systems in terms of the content and role
      of such an assessment in modern dental practice.

PMID- 15870775
TI  - Audits.

PMID- 15870776
TI  - Dental irrigators.

PMID- 15870777
TI  - Patient in pain.

PMID- 15870789
TI  - Impact factors and their significance; overrated or misused?
AB  - The journal impact factor (IF) is in widespread use for the evaluation of
      research and researchers, and considerable controversy surrounds it. The concept
      behind the IF is citations, and the number of them. The IF is a useful tool for
      the evaluation of journals, but it must be used carefully. Considerations include
      the number of review papers, letters or other types of material published in a
      journal, variations between disciplines, and item-by-item impact. Perhaps the
      most important use of the IF is in the process of academic evaluation. The extent
      to which the IF is appropriate for the evaluation of the quality of a specific
      article or journal and particularly for the evaluation of individual and
      collective research achievements is highly debatable.

PMID- 15870790
TI  - Restoration of the root-filled tooth: pre-operative assessment.
AB  - This is the first in a series of four papers related to the management of root
      canal treated teeth. When teeth compromised by extensive restorations become non
      vital, suggestions have been given as to how root canal treatment can be carried
      out with the greatest chance of success. Once root canal treated, either by a
      previous dentist or by the current dentist, a review of the assessment process
      that should be carried out prior to placing costly indirect definitive
      restorations is given. It will be clear that post-retained restorations are
      mainly reserved for anterior or single-rooted teeth, posterior teeth rarely
      requiring a post for core retention. The second paper in this series describes
      the basic tooth preparation that should be carried out prior to placing a post.
      Depending on the type of post system used, further modifications to tooth
      preparation may be required and the cementation techniques may also have to be
      modified. The third paper therefore discusses the various post types, when and
      how they should be used for optimum results. The final paper addresses
      reinforcement and restoration of compromised root canals, such as those with
      immature, open apices, or those that have been over-prepared for previous post
      retained restorations.

PMID- 15870791
TI  - Teamwork in orthodontics: limiting the risks of root resorption.
AB  - Orthodontic treatment is not without risk. The risks may be due to patient
      factors (which may not always be evident before treatment) or may come about
      because of the treatment itself. While the common types of risk are well
      documented, less information is available as to how some of the more unusual
      problems can best be managed when they arise; often the need for teamwork between
      the patient, orthodontist and general dental practitioner (GDP) are
      underestimated. This paper presents three patients in whom various root-related
      problems existed either before orthodontic treatment or which arose during
      orthodontic treatment; demonstrates how they were managed; and highlights the
      need for teamwork to ensure a 'least harmful' outcome. All patients were followed
      up for over a year.

PMID- 15870799
TI  - Tooth movement.

PMID- 15870800
TI  - Restorative dentistry.

PMID- 15870801
TI  - Policies and practices of European dental schools in relation to smoking; a ten
      year follow-up.
AB  - OBJECTIVE: To investigate the policies and practices of European dental schools
      in relation to smoking as a ten-year follow-up. DESIGN: A postal survey
      questionnaire. SETTING: European dental schools in 2003. MATERIALS AND METHODS:
      Two hundred and one European dental schools were identified from the DentEd
      database. A postal questionnaire was sent to each with up to three follow-up
      letters to non-responders. MAIN OUTCOME MEASURES: Results were tabulated and
      compared with the previous study (1993). RESULTS: The effective response rate
      (allowing for errors in the database) was 149 of 199 schools (72%). Eighty
      schools (59%) had written tobacco policies, 132 (92%) banned smoking in clinical
      areas, 127 (89%) in non-clinical areas and 122 (85%) in public access areas. One
      hundred and seven (76%) expected students to take tobacco histories from all
      patients, while 79 (69%) and 100 (70%) respectively taught students anti-smoking
      advice and expected them to give such advice. The number of schools teaching the
      role of tobacco in oral cancer aetiology was 133 (93%), in periodontal disease
      was 135 (94%) and in osseointegrated implant failure was 127 (91%). There was
      considerable regional variation between northern, southern and eastern Europe.
      Direct comparison of the responses of the 78 schools that replied in both 1993
      and 2003 showed some improvements in most of their policies and practices.
      However, there was some deterioration in the practices of southern European
      schools. CONCLUSIONS: While improvements were seen in the practices of most
      schools, comparison with recent US data suggests that European schools lag
      behind. However, self-selection of respondents may have introduced bias into the
      results.

PMID- 15870802
TI  - The survival of resin modified glass ionomer and stainless steel crown
      restorations in primary molars, placed in a specialist paediatric dental
      practice.
AB  - AIMS: To prospectively report on the survival of resin-modified glass ionomer
      cement (RMGIC), photac-fil and pre-formed stainless steel crown (SSC)
      restorations in primary molar teeth placed over a seven-year period in a
      specialist paediatric dental practice under private contract of remuneration.
      METHOD: All primary molar restorations placed by a specialist paediatric dentist
      over a seven-year period were reviewed and the outcome results recorded. Data
      were recorded at review visits until June 30, 2003. Data recorded included Class
      I restorations, Class II restorations and SSC. The Class II cavities were either
      mesial or distal, with or without buccal/palatal extensions. If both proximal
      surfaces were decayed or if after cavity preparation the resultant outline form
      was significantly larger than the minimal classical form, RMGIC was not used; an
      SSC was placed instead. Stainless steel crown preparation followed conventional
      guidelines. The crowns were cemented with reinforced zinc oxide and eugenol
      (Kalzinol). The status was recorded as satisfactory restoration, tooth
      exfoliated, tooth extracted for orthodontic reasons with the date of extraction,
      or needing replacement. If replaced then the reason for replacement was also
      recorded. RESULTS: A total of 544 Class I RMGICs, 962 Class II RMGICs, and 1,010
      SSCs were placed. At the last review of each restoration, 98.3% of Class I, 97.3%
      of Class II RMGICs and 97.0% of SSCs were either satisfactory or withdrawn
      intact. CONCLUSION: Under the conditions of private specialist practice-based
      study SSCs continued to prove very successful for the restoration of larger
      cavities and for pulp-treated primary molar teeth. For the smaller cavities RMGIC
      were also very successful.

PMID- 15870803
TI  - A study of satisfaction with dental services among adults in the United Kingdom.
AB  - OBJECTIVES: To determine satisfaction with dental care services among the UK
      adult population, and to assess their knowledge regarding the dental complaints
      procedure. METHODS: A national survey involving a multi-stage random sampling
      procedure with face-to-face home interviews of 5,385 UK residents was conducted
      in 1999. RESULTS: The response rate was 69% and 3,739 adults took part in this
      study. Majority of people (89%) were satisfied with the quality of care they
      received. Only 2% (76) had actually complained, although 10% (388) had felt like
      complaining in the past. One third (32%, 1,188) did not know to whom to complain
      if they had a problem. Among those who knew whom to contact, over a third (36%,
      1,359) would contact somebody outside the practice, while another third (31%,
      1,169) would contact their dentist or dental practice. CONCLUSION: Overall most
      people are satisfied with the quality of dental care they receive. However, 2%
      have complained and 10% have felt like complaining about their dentist/ dental
      care. In general, knowledge of the complaints procedure and whom to contact
      appears fragmented.

PMID- 15870815
TI  - New resin composites used to restore both anterior and posterior teeth.
AB  - Over the last few years, the advancements made in the field of adhesive
      techniques have significantly modified operative techniques, from cavity
      preparation to final restoration. On one hand, a predictable bond between
      restoration and dental tissues allows us to operate with very conservative
      techniques, saving sound dental tissue; on the other hand, it must be considered
      that such procedures are not simple. Additionally, it is easy to observe that all
      of our everyday dental practice is strictly influenced by the type of material
      and techniques used. Knowing such procedures as well as adhesive mechanisms,
      quality of sound dental tissue and its conservation - both in vital and
      endodontically treated teeth - is now considered significantly relevant for
      restorative purposes.

PMID- 15870816
TI  - The role of the dental surgeon in an integrated care pathway for the treatment of
      breathing difficulties.
AB  - We live in a professional environment in which the role of the dental surgeon is
      changing more rapidly than perhaps ever before. The concept of team working
      towards more efficient and focused delivery of care to our patients is one of the
      major developments, both within the practice environment through professionals
      complementary to dentistry, and indeed through medical and surgical colleagues in
      dealing with some of the wider aspects of holistic healthcare.

PMID- 15870819
TI  - Factors associated with exclusive breastfeeding in Accra, Ghana.
AB  - OBJECTIVE: To assess factors associated with exclusive breast-feeding (EBF) in
      Accra, Ghana. DESIGN, SUBJECTS, SETTING: Data on current and past infant feeding
      patterns, sociodemographic, biomedical and biocultural factors were collected
      using a cross-sectional design, from a sample of 376 women with infants 0-6
      months, attending maternal and child health (MCH) clinics in Accra. EBF was
      defined in two ways: (a) based on a 24-h recall, and (b) based on a recall of
      liquids or foods given since birth. RESULTS: Although 99.7% of mothers were
      currently breastfeeding (BF), only half (51.6%) of them EBF their infants. About
      98% of participants had heard about EBF, and 85.6% of them planned to EBF on
      delivery. Based on 'since birth' EBF, planned EBF on delivery was associated with
      higher likelihood of EBF (OR=2.56; 95% CI, 1.06-6.17) and delivery at a
      hospital/polyclinic was associated with a two times higher likelihood of EBF
      (OR=1.96; 95% CI, 1.08-3.54). Women living in their own houses were more likely
      to EBF (OR=3.96; 95% CI, 1.02-15.49) than those living in rented accommodations
      and family houses. Those with a more positive attitude towards EBF were more
      likely to EBF (OR=2.0; 95% CI, 1.11-3.57) than their counterparts with more
      negative attitudes. The '24-h recall' EBF model yielded similar results.
      CONCLUSION: In this population, EBF was associated with delivery at
      hospital/polyclinic, having secondary school education, intention to EBF prior to
      delivery, owning a home and having a positive attitude to EBF.

PMID- 15870821
TI  - Effect of L-methionine supplementation on plasma homocysteine and other free
      amino acids: a placebo-controlled double-blind cross-over study.
AB  - OBJECTIVE: The essential amino acid L-methionine is a potential compound in the
      prophylaxis of recurrent or relapsing urinary tract infection due to
      acidification of urine. As an intermediate of L-methionine metabolism,
      homocysteine is formed. The objective was to study the metabolism of L-methionine
      and homocysteine, and to assess whether there are differences between patients
      with chronic urinary tract infection and healthy control subjects. DESIGN: A
      randomized placebo-controlled double-blind intervention study with cross-over
      design. SETTING: Department of Nutritional Physiology, Institute of Nutrition in
      cooperation with the Department of Internal Medicine III, Friedrich Schiller
      University of Jena, Germany. SUBJECTS: Eight female patients with chronic urinary
      tract infection and 12 healthy women (controls). INTERVENTIONS: After a
      methionine-loading test, the volunteers received 500 mg L-methionine or a placebo
      three times daily for 4 weeks. MAIN OUTCOME MEASURES: Serum and urinary
      concentrations of methionine, homocysteine, cystathionine, cystine, serine,
      glycine and serum concentrations of vitamin B12, B6 and the state of folate.
      RESULTS: Homocysteine plasma concentrations increased from 9.4+/-2.7 micromol/l
      (patients) and 8.9+/-1.8 micromol/l (controls) in the placebo period to 11.2+/
      4.1 micromol/l (P=0.031) and 11.0+/-2.3 micromol/l (P=0.000), respectively,
      during L-methionine supplementation. There were significant increases in serum
      methionine (53.6+/-22.0 micromol/l; P=0.003; n=20) and cystathionine (0.62+/-0.30
      micromol/l; P=0.000; n=20) concentrations compared with the placebo period
      (33.0+/-12.0 and 0.30+/-0.10 micromol/l; n=20). Simultaneously, renal excretion
      of methionine and homocysteine was significantly higher during L-methionine
      intake. CONCLUSIONS: Despite an adequate vitamin status, the supplementation of
      1500 mg of L-methionine daily significantly increases homocysteine plasma
      concentrations by an average of 2.0 micromol/l in patients and in control
      subjects. An optimal vitamin supplementation, especially with folate, might
      prevent such an increase.

PMID- 15870820
TI  - Differential response of plasma and immune cell's vitamin E levels to physical
      activity and antioxidant vitamin supplementation.
AB  - OBJECTIVE: To assess the differential response of plasma, lymphocyte and
      neutrophil vitamin E levels to high-intensity physical activity and to vitamin C
      and E supplementation. SUBJECTS: In all, 14 male trained amateur runners (32-36 y
      old) were randomly divided in two groups (supplemented and placebo), and
      participated in a half marathon race. The subjects did not take any other
      supplements than the ones provided for this study. INTERVENTION: Vitamin C (152
      mg/day) and E (50 mg/day) supplementation was administrated to athletes for a
      month, using a new almond-based isotonic and energetic beverage (supplemented
      group). The usual dietary habits of participants were assessed using a self
      reported 7-day 24-h recall before the day of the study. To avoid the beverage
      influence, nonenriched vitamin C and E almond-based isotonic and energetic
      beverage was given to the placebo group. After 1 month, subjects participated in
      a half marathon race (21 km run). Vitamin E concentration was determined in
      plasma, neutrophils and lymphocytes before and immediately after the race, and 3
      h after finishing the race. RESULTS: Daily energy intake and caloric profile of
      supplemented and placebo group were not different except for vitamin C and E
      supplementation. Vitamin supplementation and exercise had no effect on vitamins E
      levels in plasma. The exercise significantly (P<0.05) increased the lymphocyte
      vitamin E concentration both in the placebo (+119%) and supplemented groups
      (+128%), and neutrophil vitamin E content in the supplemented group (+88%). These
      levels remained significantly (P<0.05) high after the short recovery. After
      exercise, vitamin E levels in lymphocytes and neutrophils of supplemented
      subjects were practically twice the levels before exercise, whereas neutrophil
      vitamin E content of the placebo group was close to those in plasma. CONCLUSION:
      After endurance exercise, lymphocytes increased their vitamin E content in the
      supplemented and placebo subjects whereas this trend in neutrophils was just
      observed in the supplemented group. The determination of vitamin E content in
      lymphocytes and neutrophils after exercise is a useful tool to assess the
      functional status of vitamin E.

PMID- 15870823
TI  - No longer 'all-or-none'.

PMID- 15870822
TI  - Bioactive food stimulants of sympathetic activity: effect on 24-h energy
      expenditure and fat oxidation.
AB  - OBJECTIVE: Bioactive food ingredients influence energy balance by exerting weak
      thermogenic effects. We studied whether the thermogenic effect of a combination
      of capsaicin, green tea extract (catechins and caffeine), tyrosine, and calcium
      was maintained after 7-day treatment and whether local effects in the gastric
      mucosa were involved in the efficacy. DESIGN: The present study was designed as a
      3-way crossover, randomised, placebo-controlled, double-blinded intervention.
      SETTING: Department of Human Nutrition, RVAU, Denmark. SUBJECTS: A total of 19
      overweight to obese men (BMI: 28.0+/-2.7 kg/m2) were recruited by advertising
      locally. INTERVENTION: The subjects took the supplements for a period of 7 days.
      The supplements were administrated as a simple supplement with the bioactive
      ingredients, a similar enterocoated version, or placebo. In all, 24-h energy
      expenditure (EE), substrate oxidations, spontaneous physical activity (SPA), and
      heart rate were measured in respiration chambers on the seventh day of each test
      period. RESULTS: After adjustment for changes in body weight and SPA, 24-h EE was
      increased by 160 kJ/day (95% CI: 15-305) by the simple preparation as compared to
      placebo, whereas the enterocoated preparation had no such effect (53 kJ/day, -92
      to 198); simple vs enterocoated versions (P=0.09). The simple preparation
      produced a deficit in 24-h energy balance of 193 kJ/day (49-338, P=0.03). Fat and
      carbohydrate oxidation were equally increased by the supplements. CONCLUSION: A
      supplement containing bioactive food ingredients increased daily EE by
      approximately 200 kJ or 2%, without raising the heart rate or any observed
      adverse effects. The lack of effect of the enterocoated preparation suggests that
      a local action of capsaicin in the gastric mucosa is a prerequisite for exerting
      the thermogenic effect.

PMID- 15870824
TI  - Screening of mutations in the CFTR gene in 1195 couples entering assisted
      reproduction technique programs.
AB  - Genetic testing of the cystic fibrosis transmembrane conductance (CFTR) gene is
      currently performed in couples undergoing assisted reproduction techniques (ART),
      because of the high prevalence of healthy carriers in the population and the
      pathogenic relationship with congenital bilateral absence of vas deferens
      (CBAVD). However, discordant data have been reported concerning the usefulness of
      this genetic test in couples with no family history of cystic fibrosis (CF). In
      this study, we report the results of CFTR molecular screening in 1195 couples
      entering ART. Genetic testing was initially carried out in a single partner of
      each couple. CFTR mutations were detected in 55 subjects (4.6%), a percentage
      that overlaps with the one reported in the general population. However,
      significantly higher frequencies of were found in CBAVD individuals (37.5%) and
      in males with nonobstructive azoospermia (6.6%). The 5T allele was found in 78
      patients (6.5%). This figure was again significantly different in males with
      nonobstructive-azoospermia (9.9%) and in those with CBAVD (100%). All together,
      139 subjects (11.6%) had either a CFTR mutation or the 5T allele. Subsequent
      molecular analysis of their partners disclosed a CFTR mutation or 5T allele in
      nine cases (6.5%). However, none of these couples had CFTR alterations in both
      members, a CFTR mutation being invariably present in one partner and the 5T
      allele in the other. In order to improve genetic counselling of these couples,
      the TG-M470V-5T association was analyzed, and a statistically significant
      relationship between 12TG-V470 and CBAVD was detected.

PMID- 15870825
TI  - High-throughput pedigree drawing.
AB  - Family trees have long been a valuable visual tool for geneticists in identifying
      clusters of inherited traits and genotypes. As more data are collected, drawing
      the graphs by hand becomes impractical and, for this reason, we have developed
      the pedigree software CraneFoot. It can process any family graph with minimal
      computational cost by making a pedigree transformation that enables the use of a
      linear node positioning algorithm. The program is designed for automated drawing
      to printed media and efficient visual classification of genetically interesting
      families from large data sets. It also incorporates a robust pedigree topology
      check with detailed error messages.

PMID- 15870827
TI  - The difference between observed and expected prevalence of MCAD deficiency in The
      Netherlands: a genetic epidemiological study.
AB  - Medium chain acyl coenzyme A dehydrogenase (MCAD) deficiency is assumed to be the
      most common inherited disorder of mitochondrial fatty acid oxidation. Few reports
      mention the difference between the expected and observed prevalence of MCAD
      deficiency on the basis of the carrier frequency in the population. We performed
      a population-wide retrospective analysis of all known MCAD-deficient patients in
      The Netherlands. In this study, the observed prevalence of MCAD deficiency in The
      Netherlands was 1/27 400 (95% confidence interval (CI) 1/23 000-1/33 900),
      significantly different from the expected prevalence of 1/12 100 (95% CI 1/8450
      1/18 500). The observed prevalence of MCAD deficiency showed a remarkable north
      south trend within the country. From the patients in this cohort, it can be
      observed that underdiagnosis contributes to a larger extent to the difference
      between the expected and observed prevalences of MCAD deficiency in our country,
      than reduced penetrance. We determined estimates of the segregation proportion in
      a cohort of 73 families under the assumption of complete ascertainment (p(LM) =
      0.41, 95% CI 0.31-0.51) and single ascertainment (p(D) = 0.28, 95% CI 0.19-0.37).
      With the expectation-maximization algorithm, a third estimate was obtained (p(EM)
      = 0.28, 95% CI 0.20-0.37). The agreement between the latter two estimates
      supports incomplete selection and the segregation proportions were in agreement
      with normal mendelian autosomal recessive inheritance.

PMID- 15870826
TI  - Disruption of Netrin G1 by a balanced chromosome translocation in a girl with
      Rett syndrome.
AB  - We have identified a girl with characteristic features of Rett syndrome (RTT) who
      carries a de novo balanced translocation involving chromosomes 1 and 7. Both
      breakpoints were mapped by fluorescence in situ hybridization with selected
      genomic clones from the regions of interest. Southern blot hybridisations,
      utilizing probes derived from breakpoint spanning BACs, detected several aberrant
      fragments specific for the patient. Sequence analysis of the cloned junction
      fragment indicated that on chromosome 1 the predominantly brain-expressed Netrin
      G1 (NTNG1) gene is disrupted, whereas on chromosome 7 there was no indication for
      a truncated gene. The chromosome 1 breakpoint lies within the 3' part of NTNG1
      and affects alternatively spliced transcripts, suggesting that the phenotype in
      this patient is the result of disturbed NTNG1 expression. In silico translation
      of the NTNG1 splice variants predicted protein isoforms with different C-termini:
      one membrane bound through a glycosylphosphatidylinositol anchor and the other
      soluble. The membrane-bound protein isoform would be affected by the breakpoint,
      whereas the soluble form would remain intact. Our results suggest that the
      central nervous system is sensitive to NTNG1 expression levels and that NTNG1 is
      a novel candidate disease gene for RTT.

PMID- 15870828
TI  - Hereditary nonpolyposis colorectal cancer: pitfalls in deletion screening in MSH2
      and MLH1 genes.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by a deficiency in
      DNA mismatch repair in consequence of germline mutations mainly in the genes MSH2
      and MLH1. Around 10% of patients suspected of HNPCC are identified with large
      genomic deletions that cannot be detected by conventional methods of mutation
      screening. The recently developed multiplex ligation-dependent probe
      amplification (MLPA) proved to be an easy to perform method for deletion
      detection and is reliable when more than one exon is deleted. We show that, in
      some cases, apparent deletions of single exons may actually result from single
      base substitutions or small insertions/deletions in the hybridisation sequence of
      MLPA probes. We conclude that single exon deletions, detected by MLPA or
      multiplex PCR, should be validated with additional methods.

PMID- 15870829
TI  - Human papillomavirus testing in cervical cancer screening.

PMID- 15870830
TI  - The assessment of antiangiogenic and antivascular therapies in early-stage
      clinical trials using magnetic resonance imaging: issues and recommendations.
AB  - Vascular and angiogenic processes provide an important target for novel cancer
      therapeutics. Dynamic contrast-enhanced magnetic resonance imaging is being used
      increasingly to noninvasively monitor the action of these therapeutics in early
      stage clinical trials. This publication reports the outcome of a workshop that
      considered the methodology and design of magnetic resonance studies, recommending
      how this new tool might best be used.

PMID- 15870831
TI  - Reduction of PTEN protein and loss of epidermal growth factor receptor gene
      mutation in lung cancer with natural resistance to gefitinib (IRESSA).
AB  - Gefitinib (IRESSA), an epidermal growth factor receptor (EGFR) tyrosine kinase
      (TK) inhibitor, has antitumour activity in the advanced non-small-cell lung
      cancer (NSCLC) setting. However, in chemotherapy-naive patients with advanced
      NSCLC, the addition of gefitinib to standard chemotherapy regimens failed to
      increase survival. These results suggest the need for improved patient selection
      and combination rationales for targeted therapies. We have identified
      subpopulations of an adenocarcinoma cell line that are naturally resistant to
      gefitinib, and have analysed the cDNA expression profiles, genomic status of EGFR
      gene and the effect of gefitinib on signalling pathways in these cell lines in
      order to identify key mechanisms for naturally acquired resistance to gefitinib.
      Gefitinib-resistant subpopulations demonstrated increased Akt phosphorylation
      (not inhibited by gefitinib), reduced PTEN protein expression and loss of the
      EGFR gene mutation when compared with parental cell lines. These differences in
      Akt and PTEN protein expression were not evident from the cDNA array profiles.
      These data suggests that (1) the EGFR gene mutation may be possibly lost in some
      cancer cells with other additional mechanisms for activating Akt, (2)
      reintroduction of PTEN or pharmacological downregulation of the constitutive PI3K
      Akt-pathway activity may be an attractive therapeutic strategy in cancers with
      gefitinib resistance.

PMID- 15870832
TI  - Loss of Ep-CAM (CO17-1A) expression predicts survival in patients with gastric
      cancer.
AB  - Preoperative staging of gastric cancer is difficult and not optimal. The TNM
      stage is an important prognostic factor, but it can only be assessed reliably
      after surgery. Therefore, there is need for additional, reliable prognostic
      factors that can be determined preoperatively in order to select patients who
      might benefit from (neo) adjuvant treatment. Expression of immunohistochemical
      markers was demonstrated to be associated with tumour progression and metastasis.
      The expression of p53, CD44 (splice variants v5, v6 and v9), E-cadherin, Ep-CAM
      (CO17-1A antigen) and c-erB2/neu were investigated in tumour tissues of 300
      patients from the Dutch Gastric Cancer Trial, investigating the value of extended
      lymphadenectomy compared to that of limited lymphadenectomy). The expression of
      tumour markers was analysed with respect to patient survival. Patients without
      loss of Ep-CAM-expression of tumour cells (19%) had a significantly better 10
      year survival (P<0.0001) compared to patients with any loss: 42% (s.e.=7%) vs 22%
      (s.e.=3%). Patients with CD44v6 (VFF18) expression in more than 25% of the tumour
      cells (69% of the patients) also had a significantly better survival (P=0.01)
      compared to patients with expression in less than 25% of the tumour cells: 10
      year survival rate of 29% (s.e.=3%) vs 19% (s.e.=4%). The prognostic value of
      both markers was stronger in stages I and II, and independent of the TNM stage.
      Ep-CAM and CD44v6-expression provides prognostic information additional to the
      TNM stage. Loss of Ep-CAM-expression identifies aggressive tumours especially in
      patients with stage I and II disease. This information may be helpful in
      selecting patients suitable for surgery or for additional treatment pre- or
      postoperatively.

PMID- 15870833
TI  - Cannabinoid agonists but not inhibitors of endogenous cannabinoid transport or
      metabolism enhance the reinforcing efficacy of heroin in rats.
AB  - Accumulating evidence suggests that the endogenous cannabinoid system is involved
      in the reinforcing effects of heroin. In rats intravenously self-administering
      heroin, we investigated effects of cannabinoid CB1 receptor agonists and
      compounds that block transport or metabolism of the endogenous cannabinoid
      anandamide. The natural cannnabinoid CB1 receptor agonist delta-9
      tetrahydrocannabinol (THC, 0.3-3 mg/kg i.p.) did not alter self-administration of
      heroin under a fixed-ratio one (FR1) schedule, except at a high 3 mg/kg dose
      which decreased heroin self-administration. Under a progressive-ratio schedule,
      however, THC dose-dependently increased the number of 50 mug/kg heroin injections
      self-administered per session and the maximal ratio completed (break-point), with
      peak increases at 1 mg/kg THC. In addition, 1 mg/kg THC increased break-points
      and injections self-administered over a wide range of heroin injection doses (25
      100 microg/kg), indicating an increase in heroin's reinforcing efficacy and not
      its potency. The synthetic cannabinoid CB1 receptor agonist WIN55,212-2 (0.3-3
      mg/kg i.p.) had effects similar to THC under the progressive-ratio schedule. In
      contrast, AM-404 (1-10 mg/kg i.p.), an inhibitor of transport of anandamide, and
      URB-597 (0.01-0.3 mg/kg i.p.), an inhibitor of the enzyme fatty acid amide
      hydrolase (FAAH) that degrades anandamide, or their combination, did not increase
      reinforcing efficacy of heroin at any dose tested. Thus, activation of
      cannabinoid CB1 receptors facilitates the reinforcing efficacy of heroin and this
      appears to be mediated by interactions between cannabinoid CB1 receptors and mu
      opioid receptors and their signaling pathways, rather than by an opioid-induced
      release of endogenous cannabinoids.

PMID- 15870835
TI  - Cortisol/dehydroepiandrosterone ratio and responses to antipsychotic treatment in
      schizophrenia.
AB  - Dehydroepiandrosterone (DHEA) or their sulfate conjugate (DHEAS) (together
      abbreviated DHEA(S)) exert multiple effects in the central nervous system, and
      may be involved in the pathophysiological processes in schizophrenia. This
      prospective study aimed to investigate whether serum cortisol/DHEA(S) molar
      ratios are associated with response to antipsychotic treatment during the
      exacerbation of schizophrenia. Serum DHEA(S) and cortisol were determined at
      baseline, and 2 and 4 weeks later for 43 medicated schizophrenia inpatients with
      acute exacerbation. The patients were treated with stable doses of antipsychotic
      agents up to 2 weeks prior to entering the study and for the 4-week duration of
      the study after which they were classified as either responders or nonresponders
      to treatment. Findings suggest that responders had significantly higher serum
      cortisol levels and cortisol/DHEA(S) ratios compared with nonresponders. These
      differences remained significant at three time points controlling for gender,
      age, severity of symptoms and emotional distress, benzodiazepines, type or dosage
      of antipsychotic agents, and background variables. The logistic regression model
      shows advantages of both cortisol/DHEA(S) molar ratios vs serum cortisol and
      DHEA(S) concentrations for prediction of responsivity to antipsychotic treatment.
      No significant canonical correlations were observed between changes from baseline
      through end-of-study in hormonal values and severity of symptoms and emotional
      distress among responders and nonresponders. Thus, these data provide evidence
      that elevated serum cortisol and cortisol/DHEA(S) ratios may serve as markers of
      biological mechanisms that are involved in responsivity of schizophrenia patients
      to antipsychotic treatment.

PMID- 15870834
TI  - Effects of low- and high-nicotine cigarette smoking on mood states and the HPA
      axis in men.
AB  - The acute effects of smoking a low- or high-nicotine cigarette on hypothalamic
      pituitary-adrenal (HPA) hormones, subjective responses, and cardiovascular
      measures were studied in 20 healthy men who met American Psychiatric Association
      Diagnostic and Statistical Manual IV criteria for nicotine dependence. Within
      four puffs (or 2 min) after cigarette smoking began, plasma nicotine levels and
      heart rate increased significantly (P<0.01), and peak ratings of 'high' and
      'rush' on a Visual Analogue Scale were reported. Reports of 'high', 'rush', and
      'liking' and reduction of 'craving' were significantly greater after smoking a
      high-nicotine cigarette than a low-nicotine cigarette (P<0.05). Peak plasma
      nicotine levels after high-nicotine cigarette smoking (23.9+/-2.6 ng/ml) were
      significantly greater than after low-nicotine cigarette smoking (3.63+/-0.59
      ng/ml) (P<0.001). After smoking a low-nicotine cigarette, adrenocorticotropin
      hormone (ACTH), cortisol, dehydroepiandrosterone (DHEA), and epinephrine did not
      change significantly from baseline. After high-nicotine cigarette smoking began,
      plasma ACTH levels increased significantly above baseline within 12 min and
      reached peak levels of 21.88+/-5.34 pmol/l within 20 min. ACTH increases were
      significantly correlated with increases in plasma nicotine (r=0.85; P<0.0001),
      DHEA (r=0.66; P=0.002), and epinephrine (r=0.86; P<0.0001). Cortisol and DHEA
      increased significantly within 20 min (P<0.05) and reached peak levels of 424+/
      48 and 21.13+/-2.55 ng/ml within 60 and 30 min, respectively. Thus cigarette
      smoking produced nicotine dose-related effects on HPA hormones and subjective and
      cardiovascular measures. These data suggest that activation of the HPA axis may
      contribute to the abuse-related effects of cigarette smoking.

PMID- 15870836
TI  - Cluster B personality disorders are associated with allelic variation of
      monoamine oxidase A activity.
AB  - Genetic variants of the monoamine oxidase A (MAOA) have been associated with
      aggression-, anxiety-, and addiction-related behavior in several nonclinical and
      clinical populations. Here, we investigated the influence of allelic variation of
      MAOA activity on aggression-related personality traits and disease risk in
      patients with personality disorders. Personality disorders were diagnosed with
      the Structured Clinical Interview of DSM-IV and were allocated to cluster A, B,
      and C. Personality features were assessed by the revised NEO Personality
      Inventory and the Tridimensional Personality Questionnaire. The genotype of the
      MAOA gene-linked polymorphic region (MAOA-LPR) was determined in 566 patients
      with personality disorders and in 281 healthy controls. MAOA genotype was
      significantly associated with cluster B personality disorders (chi2=7.77,
      p=0.005, df=1) but not with cluster C personality disorders. In total, 26.0% of
      cluster B patients were hemi- or homozygous for the low-activity variant of the
      MAOA genotype, compared to 16.4% in the control group. Associations between MAOA
      variants and personality domains related to impulsivity and aggressiveness were
      inconsistent. Our findings further support the notion that allelic variation of
      MAOA activity contributes modestly to the balance of hyper- (impulsive
      aggressive) and hyporeactive (anxious-depressive) traits.

PMID- 15870837
TI  - Ion channels in smooth muscle: regulators of intracellular calcium and
      contractility.
AB  - Smooth muscle (SM) is essential to all aspects of human physiology and,
      therefore, key to the maintenance of life. Ion channels expressed within SM cells
      regulate the membrane potential, intracellular Ca2+ concentration, and
      contractility of SM. Excitatory ion channels function to depolarize the membrane
      potential. These include nonselective cation channels that allow Na+ and Ca2+ to
      permeate into SM cells. The nonselective cation channel family includes tonically
      active channels (Icat), as well as channels activated by agonists, pressure
      stretch, and intracellular Ca2+ store depletion. Cl--selective channels,
      activated by intracellular Ca2+ or stretch, also mediate SM depolarization.
      Plasma membrane depolarization in SM activates voltage-dependent Ca2+ channels
      that demonstrate a high Ca2+ selectivity and provide influx of contractile Ca2+.
      Ca2+ is also released from SM intracellular Ca2+ stores of the sarcoplasmic
      reticulum (SR) through ryanodine and inositol trisphosphate receptor Ca2+
      channels. This is part of a negative feedback mechanism limiting contraction that
      occurs by the Ca2+-dependent activation of large-conductance K+ channels, which
      hyper polarize the plasma membrane. Unlike the well-defined contractile role of
      SR-released Ca2+ in skeletal and cardiac muscle, the literature suggests that in
      SM Ca2+ released from the SR functions to limit contractility. Depolarization
      activated K+ chan nels, ATP-sensitive K+ channels, and inward rectifier K+
      channels also hyperpolarize SM, favouring relaxation. The expression pattern,
      density, and biophysical properties of ion channels vary among SM types and are
      key determinants of electrical activity, contractility, and SM function.

PMID- 15870838
TI  - Electrical activity alterations induced by chronic absorption of lindane (gamma
      hexachlorocyclohexane) trace concentrations in adult rat heart.
AB  - The heart of adult rat offspring, born to mothers treated with trace
      concentrations of lindane (0.5 to 2 ppb) through a beverage and to mothers
      chronically treated with lindane (CL-T) with the same trace concentration, also
      through a beverage, during lactation and growth has a round shape and accumulates
      lindane. The left ventricle (LV) presents a hypertrophied area, atrophied
      papillary muscles, and unorganized collagen bundles and layers. These
      observations led us to study the electrical activity of their left ventricle
      papillary muscles (LVPM) by recording action potential using intracellular
      microelectrodes. CL-T shortened LVPM action potential duration (APD): 1 ppb
      shortened the plateau; 2 ppb shortened the plateau and the slow repolarizing
      phase. In CL-T (2 ppb) and untreated groups, low temperature (22 degrees C)
      decreased the resting potential and prolonged APD. TEA (tetraethylammonium; 1-2
      mmol/L) partially lengthened CL-T (2 ppb lindane) APD. Quinidine (0.2 mmol/L) and
      E-4031 (10 nmol/L) prolonged CL-T APD, suggesting that the rapid delayed outward
      K+ current (IKr) was increased. Our results indicate the silent effects of
      chronic exposure to trace concentrations of lindane on the morphological and
      electrical activity of heart muscle. They demonstrate that chronic lindane
      treatment of female rats alters the tissue integrity and electrical activity in
      the LV of their offspring.

PMID- 15870839
TI  - The anti-inflammatory effect of inhaled nitric oxide on pulmonary inflammation in
      a swine model.
AB  - Cardiopulmonary bypass (CPB) is associated with an inflammatory process that
      leads to lung injury. In this study, we hypothesized that inhaled nitric oxide
      (INO) possesses the ability to modulate CPB-induced inflammation. Fifteen male
      pigs were randomly divided into 3 groups: Sham, CPB+LPS (CPB and
      lipopolysaccharide), and CPB+LPS+INO. INO (20 parts per million) was administered
      for 24 h after anesthesia. CPB was performed for 90 min, and LPS was infused (1
      microg/kg) after CPB. Bronchoalveolar lavage (BAL) fluid and blood were collected
      at T0 (before CPB), at 4 h, and at 24 h. At 24 h, BAL interleukin-8 (IL-8) levels
      were not increased as expected in the CPB+LPS group compared with the Sham group,
      but they were reduced significantly in the CPB+LPS+INO group. Cell hypo
      reactivity observed in the groups receiving LPS also seemed to downregulate
      endothelial nitric oxide synthase NOS protein expression relative to the Sham
      group. Nitrite and nitrate (NOx) concentrations were decreased significantly in
      the groups without INO. Moreover, animals treated with INO showed higher rates of
      pulmonary apoptosis compared with their respective controls. These results
      demonstrate that NOx production is reduced after CPB and that INO acts on the
      inflammatory process by diminishing neutrophils and their major chemoattractant,
      IL-8. INO also increases cell apoptosis in the lungs under inflammatory
      conditions, which may explain, in part, how it resolves pulmonary inflammation.

PMID- 15870840
TI  - Endothelin A and B receptor antagonist bosentan reduces postischemic myocardial
      injury in the rat: critical timing of administration.
AB  - The purpose of this study was to investigate the effects of bosentan, a mixed
      endothelin receptor A and B subtype antagonist, on myocardial ischemia
      reperfusion injury and to explore the influence of the timing of bosentan
      administration on its cardioprotective effects. Adult rat hearts were perfused by
      the Langendorff technique with Krebs-Henseleit solution (KH) at a constant flow
      rate at 10 mL/min. Global myocardial ischemia was induced by stopping KH
      perfusion for 40 min, and this was followed by 60 min of reperfusion. Hearts were
      randomized to 1 of 3 experimental groups (n = 7 each): untreated control;
      treatment with bosentan 1 micromol/L 10 min prior to, during 40 min global
      ischemia, and for 15 min of reperfusion (BOS); or treatment with bosentan 1
      micromol/L after 15 min of reperfusion (BOS-R). We observed that BOS-R, but not
      the BOS treatment regimen, significantly reduced the release of cardiac-specific
      creatine kinase and postischemic myocardial infarct size (P < 0.05 vs. control)
      without affecting myocardial contractility. Left ventricular developed pressure
      in the BOS group was significantly (P < 0.01) lower than that in the control
      group throughout reperfusion. It is concluded that pharmacologically delayed
      antagonism of endothelin-1 during reperfusion attenuates postischemic myocardial
      injury. Endothelin-1 antagonist application during early reperfusion may
      exacerbate postischemic myocardial dysfunction.

PMID- 15870842
TI  - Activities of antioxidant enzymes in two stages of pathology development in
      sucrose-fed rats.
AB  - The activities of catalase in liver, heart and kidney as well as glutathione
      peroxidase and superoxide dismutase in liver, heart, kidney, and serum from
      hypertriglyceridemic and hypertensive female and male rats were measured at 3 and
      8 months of daily administration of sucrose in their drinking water. This
      treatment induces high levels of serum triglycerides, central obesity, moderate
      hypertension, hyperinsulinemia, and an increase in lipoperoxidation, among other
      alterations. The experimental periods were chosen on the basis of previous
      observations: at 3 months the level of serum triglycerides increases
      significantly above the normal value and remains without major changes
      thereafter, but the blood pressure only rises significantly at about 4 months in
      males and 5 months in females. So, at 8 months the rats have been subjected to
      abnormal conditions for 3-4 months. The effect of these and the influence of sex
      on levels of antioxidant enzymes were investigated. Both factors, sucrose
      treatment and sex, were conducive to significant changes in those variables.

PMID- 15870841
TI  - Effects of dopamine, SKF-38393 and R(-)-NPA on ATP-activated currents in rat DRG
      neurons.
AB  - This study aimed to investigate the effect of the activation of dopamine (DA)
      receptors on ATP-activated currents (IATP) in freshly isolated dorsal root
      ganglion (DRG) neurons of rats using whole-cell patch clamp technique in
      combination with intracellular dialysis. Extracellular application of DA
      inhibited IATP in half of the neurons tested (39/77, 50.6%), enhanced IATP in a
      small subset of the neurons (22/77, 28.6%), and had no effect on IATP in the rest
      (16/77, 20.8%). To investigate the DA receptor subtypes that mediate these
      modulations, the effects of R(-)-NPA, a D2 receptor agonist, and SKF-38393, a D1
      receptor agonist, were examined. Preapplication of R(-)-NPA inhibited IATP in
      most of the cells tested (53/57, 93.0%) and had no effect in the rest (4/57,
      7.0%); no potentiating effect was observed. Preapplication of SKF-38393 inhibited
      IATP in a majority of the cells tested (57/77, 74.0%), potentiated IATP in some
      cells (12/77, 15.6%), and had no effect in the remainder (8/77, 10.4%). Further
      study of the inhibitory effect of R(-)-NPA and SKF-38393 revealed that both of
      them acted in a noncompetitive manner, shifting the concentration-response curve
      for IATP downwards with the maximal response markedly reduced and EC50 basically
      unchanged; and the inhibition was independent of the holding potential.
      Intracellular dialysis of GDP-beta-S and H-7 abolished R(-)-NPA inhibition of
      IATP completely, and SKF-38393 inhibition of IATP was removed by intracellular
      application of H-7 but not by H-9. These results suggest that the activation of
      DA receptors dominantly inhibits IATP in dorsal root ganglion cells, and this
      inhibition may be involved in the modulation of afferent information by the
      diencephalon-derived DA in the primary sensory neurons.

PMID- 15870843
TI  - Ischemia-reperfusion injury stimulates gelatinase expression and activity in
      kidney glomeruli.
AB  - Although ischemia remains the leading cause of acute renal failure in humans,
      there is little information on the expression and activities of gelatinases of
      kidney glomeruli during ischemia-reperfusion injury. In this study, we used a
      unilateral ischemia-reperfusion model to investigate the activity and expression
      of gelatinases in glomeruli during acute ischemia. Unilateral ischemia was
      induced in rats by vascular clamping (30 min) followed by reperfusion (60 min)
      and isolation of glomeruli. The activity and expression of gelatinase proteins
      were determined by gelatin zymography and Western blotting. Gelatinase mRNA
      levels were evaluated by reverse transcriptase-PCR. Ischemia and reperfusion
      increased serum creatinine levels, hallmark of acute renal failure. Ischemia
      induced mRNA and protein MMP-2 expression. There was strong stimulation of MMP-9
      mRNA, both forms of dimeric MMP-9, and active monomeric MMP-9. In contrast to
      TIMP-1 decreasing, TIMP-2 protein and mRNA increased during ischemia. During
      reperfusion, there was a gradual reversal of the MMP-2 and MMP-9 levels and a
      strong inhibition of TIMP-1 and TIMP-2 at the protein and mRNA levels. Endocytic
      receptor LRP was increased during ischemia and returned to normal during
      reperfusion. Expression of MMP-9 docking receptor CD-44 was increased during
      reperfusion. Finally, ZO-1, an in vivo MMP-9 substrate, was degraded during
      ischemia, revealing that MMP-9 upregulated during ischemia was functional. Our
      data suggest that stimulation of gelatinase activity during ischemia could
      contribute to glomeruli injury, providing new therapeutic targets for acute renal
      failure in humans. In contrast, elevated monomeric MMP-9 activity due to TIMP-1
      decrease during reperfusion may participate to glomerular recovery.

PMID- 15870844
TI  - Inhibition of gelatinase B (matrix metalloproteinase-9) by dihydrolipoic acid.
AB  - Alpha-lipoic acid (LA) is a disulphide-containing fatty acid that is absorbed
      from the diet and transported to tissues. Once it has been taken up by mammalian
      cells, LA is reduced to dihydrolipoic acid (DHLA), a vicinal dithiol, and rapidly
      effluxed into the extracellular milieu. We hypothesized that DHLA may be an
      effective inhibitor of human gelatinase B (GelB). Purified human GelB was
      incubated with 0 to 200 micromol/L DHLA, and residual enzyme activity was
      measured by HPLC using a fluorogenic substrate (matrix metalloproteinase
      substrate III). DHLA inhibited GelB in a dose-dependent fashion with an IC50 of
      20 micromol/L. Oxidation of DHLA resulted in a loss of DHLA's capacity to inhibit
      GelB. The DHLA-mediated inhibition of GelB was independent of the zinc
      concentration in the reaction buffer. DHLA had no inhibitory effect on gelatinase
      A. Zymographs of activated neutrophil lysates demonstrated that higher
      concentrations of DHLA also prevent the activation of GelB proenzyme.
      Bronchoalveolar lavage fluid from mice fed a diet enriched with LA showed
      significantly increased GelB inhibitory capacity (p = 0.0002 vs. regular diet).
      We conclude that DHLA can modulate neutrophil-derived GelB activity through
      direct inhibition of enzyme activity and by preventing the activation of GelB
      proenzyme.

PMID- 15870845
TI  - Proanthocyanidin from grape seeds enhances doxorubicin-induced antitumor effect
      and reverses drug resistance in doxorubicin-resistant K562/DOX cells.
AB  - With the aim of enhancing the efficacy of chemotherapeutic agents, we
      investigated the antitumor actions and reversal effect on drug resistance of
      proanthocyanidin plus doxorubicin. The results showed that proanthocyanidin 12.5
      200 mg/L significantly inhibited proliferation of K562, K562/DOX, SPC-A-1, and
      Lewis cells in vitro in a time- and concentration-dependent manner, as determined
      by microculture tetrazolium assay. A combination of proanthocyani din 12.5, or 25
      mg/L and doxorubicin treatment synergistically inhibited cell proliferation with
      decreased IC50 values. Proanthocyanidin reverses drug resistance in doxorubicin
      resistant K562/DOX cells, and IC50 values were decreased by 9.19 (3.64-23.19),
      2.56 (1.48-.44), and 0.94 (0.81-1.09) mg/L, respectively, after 24 h treatment
      with doxorubicin 0.1-9.0 mg/L alone or in combination with proanthocyanidin 12.5
      or 25 mg/L; the proanthocyanidin reversal fold was 3.6 and 9.8, respectively.
      Under confocal laser scanning microscope, the combination of proanthocyanidin 25
      or 50 mg/L with doxorubicin 3 mg/L significantly increased the accumulation of
      intracellular doxorubicin, Ca2+, and Mg2+, and reduced the pH value and
      mitochondrial membrane potential in K562/DOX cells as compared with doxorubicin
      alone (p < 0.01). Additionally, the apoptosis rate was increased by 11.3% +/-
      3.3%, 14.2% +/- 5.4%, and 23.8% +/- 2.8%, respectively, for doxorubicin 3 mg/L
      alone or with proanthocyanidin 12.5 or 25 mg/L, as compared with controls (3.0%
      +/- 1.4%), as demonstrated by flow cytometry. In vivo experiments demonstrated
      that i.p. administration of proanthocyanidin 10 mg/kg with doxorubicin 2 mg/kg
      had an inhibitory effect on the growth of transplantation tumor sarcoma 180 and
      hepatoma 22 in mice as compared with doxorubicin alone (p < 0.05). These results
      suggest that proanthocyanidin enhances doxorubicin-induced antitumor effect and
      reverses drug resistance, and its mechanism is attributed partially to the
      promotion of doxorubicin-induced apoptosis through an elevation of intracellular
      doxorubicin, and Ca2+, Mg2+ concentration, and a reduction of pH value and
      mitochondrial membrane potential.

PMID- 15870847
TI  - Clinical holistic medicine: whiplash, fibromyalgia, and chronic fatigue.
AB  - Holistic treatment of the highly complex, "new diseases" are often possible with
      the tools of consciousness-based medicine. The treatment is more complicated and
      the cure usually takes longer than for less-complex diseases. The problem with
      these patients is that they have less easily accessible resources than most
      patients, as they suffer from a combined socio-psycho-physical problem with
      depression, poor social standing, low confidence, and low self-esteem. Often,
      they have also already tried most of the specialist and alternative treatments on
      the market. To cure them, the most important thing is to coach them to improve
      their social life by changing their behavior to be of more value to others.
      Holding and processing must be especially careful and the contract with the
      patients must be extremely explicit in order to work on their personal
      development for 6-12 months. The new diseases can be cured with consciousness
      based medicine if the patients are motivated and keep their appointments and
      agreements. Low responsibility, low personal energy, little joy of life, and
      limited insight into self and existence are some of the features of the new
      diseases that make them difficult to cure. The important thing is to keep a pace
      the patient can follow and give the patient a row of small successes and as few
      failures as possible. The new diseases are a challenge, a unique chance to
      improve communication, holding, and processing skills.

PMID- 15870848
TI  - Ultraviolet fluorescence spectra of fingerprints.
AB  - We have studied inherent fluorescence spectra and imaging of fingerprints in the
      deep ultraviolet (UV) region with a nanosecond-pulsed Nd-YAG laser system that
      consists of a tunable laser, a cooled CCD camera, and a grating spectrometer. In
      this paper, we have studied UV fluorescence spectra of fingerprints under 266-nm
      illumination. Fluorescence spectra of fingerprints have two main peaks, around
      330 nm (peak A) and 440 nm (peak B). At first, when a fingerprint has just been
      pressed, peak A is dominant. However, its intensity reduces as the total
      illumination time increases. On the other hand, peak B is weak at first. It
      appears after enough 266-nm illumination and its intensity increases as time
      elapses. After 3 h of illumination, peak A almost diminishes and peak B becomes
      dominant. By leaving the fingerprint under a fluorescent lamp in a room without
      laser illumination, peak A can be restored partly, while the intensity of peak B
      still increases. Time-resolved fluorescence spectra were also measured for these
      two peaks. The lifetime of each peak is 2.0 nsec (peak A) and 6.2 nsec (peak B)
      on average. Both peaks seem to consist of several components with different
      lifetimes. In the case of peak A, the 330-nm peak decays fast and a new component
      at 360 nm becomes dominant when the delay time exceeds 20 nsec. In the case of
      peak B, unlike peak A, no clear peak separation is observed, but the peak
      position seems to move from 440 to 460 nm when the delay time becomes larger.

PMID- 15870849
TI  - Transient hydroureteronephrosis caused by a Foley's catheter tip in the right
      ureter.
AB  - We report a case of unilateral hydronephrosis following urethral catheterization
      in a patient with T6 complete paraplegia at the Physical Medicine and
      Rehabilitation Department in a tertiary care teaching hospital, India. Diagnosis
      was established by an abdominal ultrasound. The misplaced catheter tip was
      withdrawn from the ureteric orifice and hydronephrosis was resolved. Foley's
      catheterization, a widely practiced clinical procedure, is not without its
      attendant risks of an inadvertent placement in the ureter leading to transient
      hydronephrosis. Inadequate drainage through a catheter should thus alert one to
      this potentially hazardous complication that can be diagnosed by an early
      ultrasound. This complication can be avoided by gently tugging on the catheter
      after inflating the catheter bulb.

PMID- 15870853
TI  - A new long-chain UV absorber derived from 4-tert-butyl-4'
      methoxydibenzoylmethane: absorbance stability under solar irradiation.
AB  - A new UV filter, the 1-(4-tert-butylphenyl)-2-decanyl-3-(4'-methoxyphenyl)
      propane 1,3-dione called C10-DBM, was prepared by grafting a ten-carbon aliphatic
      chain to the alpha-carbonyl position of 4- tert -butyl-4'-methoxydibenzoylmethane
      (BM-DBM).(1) UVA absorption efficiency of a cosmetic preparation containing this
      new filter, called C10-DBM, was tested and compared to an identical preparation
      containing BM-DBM. The two preparations were irradiated under a 150-W xenon lamp
      or exposed to natural sunlight. The originality of this new filter resided in
      that its UVA absorbance appeared during the irradiation of the molecule.
      Moreover, although the molar absorption coefficient of C10-DBM in the UVA domain
      was lower than that of BM-DBM, its absorption showed much more photostable
      behavior under both methods of irradiation. After two hours of sunlight exposure,
      the preparation containing the BM-DBM lost 85% of its UVA absorbance, whereas the
      UVA absorbance of the preparation containing C10-DBM showed a decrease of 3% in
      comparison to the maximum absorbance obtained after 30 minutes of irradiation.
      Also, after two hours of exposure to natural sunlight, the UVA absorbance of the
      preparation containing C10-DBM remained above its initial value (before the
      irradiation began).

PMID- 15870856
TI  - Folic acid and colorectal cancer prevention: molecular mechanisms and
      epidemiological evidence (Review).
AB  - Epidemiological studies suggest that a diet rich in fruits and vegetables
      protects against colorectal cancer. This effect may result from their high levels
      of folic acid (pteroylglutamic acid). Folic acid holds a key position in DNA
      synthesis and mitosis as well as DNA methylation and regulation of gene
      expression. Folic acid deficiency has been associated with site- and gene
      specific DNA hypo- and hypermethylation. Furthermore thymidylate synthesis is
      restricted by folic acid deficiency which causes misincorporation of nucleotides
      and DNA strand breaks. Much epidemiological evidence supports the hypothesis that
      insufficient folic acid supply favors the development of colorectal tumors,
      particularly prospective studies have supported this connection. However, the
      data from case-control studies are less consistent. Functional polymorphisms in
      folate-metabolizing genes, especially the methylenetetrahydrofolate reductase
      (MTHFR) are capable of modifying the risk of colorectal cancer. Observational
      studies show that individuals with the homozygote genotype for the MTHFR (677C-
      >T) polymorphism are at higher risk when folic acid supply is low. Currently
      there are only few human intervention trials which show that folic acid can
      modify and inhibit the development of colorectal tumors. Additional studies are
      required in order to determine whether folic acid will be a useful agent in
      colorectal cancer prevention.

PMID- 15870858
TI  - Oncolysis of vascular malignant human melanoma tumors by Coxsackievirus A21.
AB  - Cultured melanoma cell lines despite exhibiting similar in vitro morphology,
      display significant phenotypic and growth rate differences when propagated as in
      vivo xenografts. Previously we have shown that Coxsackievirus A21 (CVA21)
      lytically infects in vitro cultures of malignant melanoma cells and is efficient
      at reducing the tumor burden of mice bearing slow-growing SK-Mel-28 melanoma
      xenografts. The oncolytic activity of CVA21 against in vivo melanoma xenografts,
      which possess rapid growth rates and more extensive vascular structure than SK
      Mel-28 xenografts warrants further investigation. In the present study we
      evaluated the oncolytic action of CVA21 against rapidly growing melanoma
      xenografts (ME4405) which exhibit a highly vascular phenotype. Flow cytometric
      analysis indicated that in vitro cultures of ME4405 cells expressed comparable
      levels of the CVA21 cellular receptors, ICAM-1 (intercellular adhesion molecules
      1) and DAF (decay accelerating factor) to SK-Mel-28 cells. Despite similar levels
      of CVA21 receptor expression, SK-Mel-28 cells appear to be more susceptible to
      viral lysis than ME4405 cells, even though the kinetics of virus replication in
      both lines was comparable. Intratumoral, intraperitoneal or intravenous
      administration of CVA21 were equally effective in reducing the tumor volume of
      ME4405 xenografts in immunodeficient mice, and provides further evidence for the
      use of CVA21 as a novel oncolytic agent against varying phenotypes of malignant
      melanoma.

PMID- 15870857
TI  - Expression of bone morphogenetic protein 2 in breast cancer cells inhibits
      hypoxic cell death.
AB  - BMP-2 is involved in the fetal and postnatal development of the mammary gland but
      has also been detected in breast cancer cells. To clarify the biological role of
      BMP-2 in breast cancer, we used the human breast cancer cell line MCF-7.
      Incubation with BMP-2 under serum-free conditions induced activation of the
      mitogen activated protein kinases (MAPKs) ERK1/2 and the basic helix-loop-helix
      transcription factors Id-1, proteins that can protect from apoptosis. Stably
      transfected MCF-7 cells overexpressing BMP-2 revealed significantly increased
      resistance to hypoxia-induced apoptosis compared to empty vector controls.
      Cytoplasmic BMP-2/4 protein expression was detected in carcinoma cells of 81
      samples of invasive breast cancer in contrast to adjacent normal mammary
      epithelial cells. BMP-2/4 expression did not correlate with common prognostic
      parameters and was not associated with relapse-free or overall survival. We
      conclude that BMP-2/4 expression is reactivated in invasive breast cancer and
      part of an autocrine/paracrine mechanism rescuing malignant cells from hypoxic
      cell death via activation of the MAPK and Id-1 pathway.

PMID- 15870859
TI  - Hypoxia-regulated glucose transporter Glut-1 may influence chemosensitivity to
      some alkylating agents: results of EORTC (First Translational Award) study of the
      relevance of tumour hypoxia to the outcome of chemotherapy in human tumour
      derived xenografts.
AB  - Tumour hypoxia confers poor prognosis in a wide range of solid tumours, due to an
      increased malignancy, increased likelihood of metastasis and treatment
      resistance. Poorly oxygenated tumours are resistant to both radiation therapy and
      chemotherapy. However, although the link between radiation therapy and hypoxia is
      well established in a range of clinical studies, evidence of its influence on
      chemotherapy response is lacking. In this study, a panel of human tumour-derived
      xenografts that have been characterised previously for in vivo response to a
      large series of anti-cancer agents, and have been found to show
      chemosensitivities that correlate strongly with the parent tumour, were used to
      address this issue. Immunohistochemistry was carried out on formalin-fixed,
      paraffin-embedded sections of xenograft samples to detect expression of the
      intrinsic hypoxia marker Glut-1 and adducts of the bioreductive hypoxia marker
      pimonidazole. Glut-1 scores correlated significantly with T/C values for CCNU
      sensitivity (r = 0.439, P = 0.036, n = 23) and showed a borderline significant
      correlation with dacarbazine T/C (r = 0.405, P = 0.076, n = 20). However, there
      was no correlation between both Glut-1 and pimonidazole scores and T/C obtained
      for the bioreductive drug mitomycin C. The use of human tumour-derived xenografts
      offers a potentially useful way of using archival material to determine the
      influence of hypoxia and other tumour-microenvironmental factors on
      chemosensitivity without the direct use of human subjects.

PMID- 15870860
TI  - Dual lympho-myeloproliferative disorder in a patient with t(8;22) with BCR-FGFR1
      gene fusion.
AB  - The case of a patient presenting with a myeloproliferative disorder (MPD)
      characterized by a t(8;22) (p12;q11) translocation was investigated. The
      rearrangement resulted in the production of BCR-FGFR1 and FGFR1-BCR chimeric
      transcripts after in-frame fusions of BCR exon 4 with FGFR1 exon 9 and FGFR1 exon
      8 with BCR exon 5, respectively. The four previously reported patients with such
      translocation presented with an atypical chronic myeloid leukemia (CML) without
      Philadelphia chromosome. In addition to a myeloproliferation, the patient had a B
      cell proliferation. The phenotypic characterization of the lymphoid cells in the
      bone marrow showed a continuum of maturation from blast B cells to polyclonal
      lymphocytes. In the blood, B cells showed a complete polyclonal maturation. The
      BCR-FGFR1 gene fusion was detected by dual-color fluorescence in situ
      hybridization in both CD19- and CD19+ populations. In contrast to the other FGFR1
      MPDs that show myeloid and T cell proliferation, we propose that this t(8;22) MPD
      is a myeloid and B cell disease, and potentially a novel type of hematological
      disease. Although the FGFR1-MPD is rare, its study provides interesting clues to
      the understanding of hematopoietic stem cell biology and oncogene activation.

PMID- 15870861
TI  - Promoter hypermethylation of p16INK4a, E-cadherin, O6-MGMT, DAPK and FHIT in
      adenocarcinomas of the esophagus, esophagogastric junction and proximal stomach.
AB  - Although the incidence of Barrett's carcinomas (BC) and proximal gastric
      adenocarcinomas (PGC) is increasing, little is known about different epigenetic
      changes in these etiopathogenetically distinct entities. Therefore, 29
      adenocarcinomas [10 BC, 7 PGC and 12 tumors of the esophagogastric junction (JC)]
      and corresponding non-tumor controls (NT) were examined using methylation
      specific PCR. The most striking result was a significantly higher promoter
      methylation frequency of O6-methylguanine methyl transferase (MGMT) in BC
      compared with JC and PGC (0.7 vs. 0.08 vs. 0.29, respectively; p = 0.011;
      methylation exclusively in tumors), confirmed immunohistochemically by a
      significant loss of MGMT protein in BC (p = 0.006). Therefore, MGMT might become
      a prognosticator and key for chemotherapy with alkylating agents in BC.
      Frequencies of p16INK4a promoter methylation were 0.5 (BC), 0.42 (JC) and 0.29
      (PGC; n.s.), but methylation was almost absent in NT controls. As immunonegative
      tumors slightly outnumber methylation-positive cases, other mechanisms of gene
      inactivation must be discussed. Methylation of E-cadherin was rarely observed
      (1/10 BC, 0/12 JC and 2/7 PGC). This is the first report on promoter methylation
      of death-associated protein kinase (DAPK) and fragile histidine triad gene (FHIT)
      in BC; both DAPK (BC 0.7, JC 0.92 and PGC 0.86) and FHIT (BC 0.88, JC 1.0 and PGC
      1.0) were found to be highly methylated, suggesting that epigenetic silencing of
      these tumor suppressors is a common event in adenocarcinomas of the upper
      gastrointestinal tract, including BC. DAPK (0.54 on average) and FHIT methylation
      (0.77 on average) were also observed in NT samples. This might constitute an
      early epigenetic precursor lesion in the normally-appearing tissue surrounding
      the tumor.

PMID- 15870862
TI  - Photodynamic diagnosis of a human nasopharyngeal carcinoma xenograft model using
      the novel Chlorin e6 photosensitizer Fotolon.
AB  - The current study investigates the potential of the photosensitizer Fotolon as a
      photodynamic diagnostic agent in an in vivo system of human nasopharyngeal
      carcinoma (NPC) cells. Fotolon (formerly known as Photolon) represents a complex
      of trisodium salt Chlorin e6 and polyvinylpyrrolidone (PVP). It is a
      photosensitizing agent that selectively accumulates in tumour tissues. A poorly
      differentiated human nasopharyngeal carcinoma cell line CNE-2 was xenografted on
      6-8 weeks old male balb/c nude mice for our photodynamic diagnostic (PDD)
      studies. A fluorescence endoscope system was used to perform the in vivo
      macroscopic fluorescence digital imaging of tumours on the mice. The macroscopic
      images were further analyzed for distribution of fluorescence intensity. Laser
      fluorescence confocal microscopy was used to capture microscopic fluorescence
      images of the tumour tissue. In our PDD studies, we observed intense fluorescence
      in the tumour and tumour vasculature of human NPC xenografts on nude mice as
      early as 15-min post administration of Fotolon. High fluorescence selectivity in
      the tumour tissue was observed between 3-h and 6-h time points. The tumour to
      normal tissue selectivity ratio was highest at 6 h. The microfluorescence tumour
      imaging shows similar trends confirming the macroscopic fluorescence data.
      Fotolon shows much promise as a good photodiagnostic agent.

PMID- 15870863
TI  - The estrogenic activity of synthetic progestins used in oral contraceptives
      enhances fatty acid synthase-dependent breast cancer cell proliferation and
      survival.
AB  - Overexpression of the lipogenic enzyme fatty acid synthase (FAS) is a common
      molecular feature in subsets of sex-steroid-related tumors including breast
      carcinomas that is associated with poor prognosis. In this study, we explored
      whether breast-cancer associated FAS (oncogenic antigen-519) is regulated by the
      progestin component in oral contraceptives. In addition, we examined the role of
      FAS hyperactivity on progestin-regulated breast cancer cell proliferation,
      survival and metastatic properties. We found that in estrogen receptor (ER)- and
      progesterone receptor (PR)-positive MCF-7 human breast cancer cells, synthetic
      progestins used in oral contraceptives including norethynodrel (NOR) and
      norethindrone, induced a dose-dependent increase of FAS enzymatic activity, with
      a maximum response (> or = 4-fold) occurring at a concentration of 10(-8) M. FAS
      activity was only slightly stimulated after exposure to two other progestins,
      medroxy-progesterone acetate (MPA) and megestrol acetate (MGA), which are used in
      postmenopausal hormone replacement therapy and high-dose progestin treatment
      therapy. Western blot analyses showed that NOR-induced stimulation of FAS
      activity correlated closely with NOR-induced up-regulation of FAS protein
      expression. To determine the role of FAS accumulation following NOR exposure, we
      pharmacologically examined the requirement for FAS activity in NOR-stimulated
      breast cancer cell proliferation and survival. The novel small compound C75 (a
      slow-binding FAS inhibitor) blocked NOR-induced breast cancer cell proliferation
      in anchorage-dependent assays. More importantly, pharmacological inhibition of
      FAS activity completely abolished NOR-stimulated soft-agar colony formation of
      MCF-7 cells. To evaluate the involvement of PR and ER signalings in NOR-induced
      up-regulation of FAS expression and activity, NOR was used in combination with
      either the anti-progestin RU486 (mifepristone) or the pure antiestrogen ICI
      182,780 (Faslodex). RU486 and ICI 182,780 similarly abolished NOR-induced FAS
      activation, supporting the notion that PR- and ER-mediated FAS up-regulation
      might play different roles in NOR-stimulated breast cancer cells. Interestingly,
      when we evaluated the involvement of PR and ER signalings on NOR-induced breast
      cancer cell proliferation, the anti-estrogen ICI 182,780, but not the anti
      progestin RU486, was found to inhibit NOR-stimulated proliferation and survival
      of MCF-7 cells in anchorage-dependent and -independent assays. To further
      determine whether NOR produced their effects via the ER, we evaluated its effects
      on endogenous ER transcriptional activity by using transient transfection assays
      with an estrogen-response element reporter construct (ERE-Luciferase). In the
      absence of E2 stimulation, treatment with NOR dramatically increased the levels
      of ERE-dependent transcriptional activity. This estrogenic like-effect of NOR was
      blocked by the addition of ICI 182,780, whereas RU486 failed to inhibit NOR
      induced ERE activity. In summary, this study provides direct evidence that: a) a
      number of synthetic progestins used in oral contraceptives significantly
      activates breast cancer-associated FAS (OA-519) activity and expression in
      hormone-dependent breast cancer cells; b) FAS activity is necessary for progestin
      induced anchorage-independent growth and survival of human breast cancer cells,
      and c) activation of ER, but not PR signaling, is the stimulatory mechanism
      through which synthetic progestins enhance a FAS-dependent proliferative and pro
      survival signaling. These findings should be helpful to explain the conflicting
      evidence linking oral contraceptives and breast cancer risk through the
      estrogenic activation of tumor-associated FAS (OA-519), a molecular marker
      associated with poor clinical outcome of breast cancer disease.

PMID- 15870864
TI  - Cell binding isoforms of vascular endothelial growth factor-A (VEGF189)
      contribute to blood flow-distant metastasis of pulmonary adenocarcinoma.
AB  - Vascular endothelial growth factor A (VEGF-A) has two kinds of isoforms depending
      on cellular binding domains. VEGF189 is the largest molecule with the strongest
      cellular binding ability, and is thought to be most potent for vascularization in
      various cancers. This study aims to clear the clinicopathological characteristics
      of VEGF189 in the pulmonary adenocarcinoma. We finely and quantitatively examined
      the expression of VEGF-A isoforms (VEGF121, VEGF165 and VEGF189) by real-time
      polymerase chain reaction in a total of 100 pulmonary adenocarcinomas resected by
      surgical operation. The VEGF isoform expression status was analyzed on
      clinicopathological features including stromal vascularization, vascular
      involvement, distant metastasis, lymph nodal metastasis, postoperative relapse
      time and prognosis of long-term observation periods. All the pulmonary
      adenocarcinomas showed significant expression of VEGF-A. Twenty-two cases with
      the adenocarcinomas overexpressing VEGF-A significantly showed earlier
      postoperative relapse and poorer prognosis between 5- to 15-year periods (p =
      0.0093 and p = 0.0240, Kaplan Meier, log-rank test). The expression levels of
      VEGF189 increased in 13% of the pulmonary adenocarcinoma. These 13 cases with
      increased VEGF189 expression significantly showed higher distant metastases,
      earlier postoperative relapse, and poorer prognosis (p = 0.0006, Fisher's test; p
      = 0.0016 and p = 0.0084, Kaplan Meier, log-rank test) than the other 87 cases.
      The 13 lung cancers with VEGF189 overexpression also showed increased vessel
      counts, areas (p = 0.0091 and p < 0.0001, Mann-Whitney U test) and enhanced
      venous involvement (p = 0.0056, Fisher's test). The cellular binding isoform
      VEGF189 confers pulmonary adenocarcinoma patients with poorer prognosis with
      distant metastasis via blood flow.

PMID- 15870865
TI  - Cox-2 and Her2/neu co-expression in invasive bladder cancer.
AB  - We examined the expression of Her2/neu and Cox-2 in bladder cancer and its
      relationship to clinicopathological factors, survival data and patient outcome.
      From 153 consecutive patients who had undergone radical cystectomy for bladder
      cancer, tumour tissue was analysed for Her2/neu amplification by fluorescent in
      situ hybridisation and for Her2/neu and Cox-2 protein expression by
      immunohistochemistry. Results were correlated with clinical data and survival
      times. Cox-2 and Her2/neu co-expression was present in 44 (33%) of 132
      transitional cell carcinomas. Although this association was significant (p =
      0.003), there was no significant association between Cox-2 and Her2/neu
      amplification status. Each marker was independent of primary tumour stage and
      lymph node status, as well as histological grading. However, the co-existence of
      Her2/neu amplification and Cox-2 expression correlated with distant metastases:
      of 5 Cox-2-positive samples, 2 (40%) showed Her2/neu amplification. This was only
      a trend, amounting to no more than borderline statistical significance (p =
      0.046). Kaplan-Meier survival analysis did not demonstrate any relationship
      between Cox-2 or Her2/neu expression or amplification alone or in combination
      with respect to overall and disease-free survival. Analysing the co-expression of
      Cox-2 and Her2/neu status does not add any prognostic information in patients
      with bladder cancer. Nevertheless, combined treatment with Her2/neu and Cox-2
      inhibitors may be beneficial for the subgroup of Her2/neu- and Cox-2-expressing
      tumours and will have to be assessed in further preclinical and clinical studies.

PMID- 15870866
TI  - Wilfoside K1N isolated from Cynanchum wilfordii inhibits angiogenesis and tumor
      cell invasion.
AB  - Wilfoside K1N is a polyoxypregnane glycoside isolated from Cynanchum wilfordii
      (Asclepiadaceae). Polyoxypregnane glycosides are associated with cellular
      immunity and anti-tumor activity, and increase the cytotoxicity of many anti
      cancer drugs showing multidrug resistant activity on tumor cells. In the present
      study, we investigated the anti-angiogenic and anti-invasive activities of
      wilfoside K1N. In in vivo Matrigel plug assay using C57BL/6 mice, wilfoside K1N
      strongly inhibited basic fibroblast growth factor-induced microvessel formation.
      Exposure of wilfoside K1N to human umbilical vein endothelial cells (HUVEC)
      suppressed in vitro tube formation at a concentration not affecting cell
      viability. Moreover, wilfoside K1N significantly reduced the proliferation of
      HUVEC and calf pulmonary artery endothelial cells. In addition, wilfoside K1N
      decreased in vitro invasion of HT1080 human fibrosarcoma cells, and the
      inhibition might be through down-regulation of activity as well as quantity of
      matrix metalloproteinase-9. Therefore, our present study suggests that wilfoside
      K1N may have a potential to have strong anti-angiogenic and anti-invasive
      activities both in vitro and in vivo.

PMID- 15870867
TI  - The zinc-finger transcription factor Snail downregulates proliferating cell
      nuclear antigen expression in colorectal carcinoma cells.
AB  - The Snail family of zinc-finger protein is a transcription repressor that is
      involved in the development of vertebrate and invertebrate embryos as well as in
      tumor progression. This family leads to broad biological functions such as cell
      differentiation, cell motility, cell cycle regulation and apoptosis. However, the
      target genes of Snail remain little known. In this study, we found several
      potential Snail binding sequences in the 5'-flanking region of human PCNA gene.
      Cotransfection experiments showed that Snail reduces human PCNA gene promoter
      activity in colorectal carcinoma cell lines, HCT116 and Colo320HSR. Snail-reduced
      PCNA expression was detected in immunoblotting and immunochemistry. In BrdU
      incorporation experiment, Snail inhibited the BrdU incorporation. Electrophoretic
      mobility shift assays showed that Snail can bind to the potential Snail
      recognition sites in the human PCNA promoter. Taken together, our results suggest
      that Snail may have an inhibitory effect on cell proliferation through down
      regulation of PCNA expression as a novel target.

PMID- 15870868
TI  - ILK as a potential marker gene to ascertain specific adenocarcinoma cell mRNA
      isolation from frozen prostate biopsy tissue sections.
AB  - A major technical challenge related to gene expression profiling of tissue
      samples is the difficulty of procuring selected cell populations from tissues
      that by nature are heterogeneous, such as prostate tissue. In this study we have
      examined the expression of integrin-linked kinase (ILK) mRNA in prostate
      adenocarcinoma cells versus normal prostate epithelial cells in order to
      determine whether ILK could be used as a reference marker gene for prostate
      adenocarcinoma cell mRNA isolation. Using laser microdissection (LMD) technology
      and real-time PCR, together with immunohistochemistry, we have analyzed ILK mRNA
      expression in epithelial cells isolated from frozen prostate biopsy specimens as
      well as 4 prostate cell lines (RWPE-1, LNCaP, PC-3 and DU 145) and correlated ILK
      mRNA expression with ILK protein expression. We demonstrate that quantitative
      upregulation of ILK mRNA expression in prostate epithelial cells derived from
      prostate tissue correlated with ILK protein expression and with the
      histopathology diagnosis of prostate adenocarcinoma. We further show that the
      level of ILK overexpression was directly influenced by the method used to isolate
      prostate adenocarcinoma cells (bulk tissue versus LMD dissected cells). These
      data provide evidence that ILK mRNA is quantitatively upregulated in prostate
      adenocarcinoma cells versus normal epithelial cells and is therefore a useful
      internal reference gene marker to evaluate the quality of prostate adenocarcinoma
      cell derived mRNA used for large scale prostate cancer cDNA gene profiling.

PMID- 15870869
TI  - Cutaneous CD56 positive natural killer and cytotoxic T-cell lymphomas.
AB  - We report two cases of CD56 positive natural killer (NK) cell and cytotoxic T
      cell cutaneous lymphomas and review the literature on these rare forms of non
      Hodgkin's lymphoma. The first case was diagnosed to have extra nodal NK/T-cell
      lymphoma, nasal-type. She had a rapid downhill clinical course and died within 3
      months of presentation. She had been started on systemic chemotherapy but did not
      respond. The second case was diagnosed as subcutaneous panniculitis-like T-cell
      lymphoma, CD56 positive variant. She presented with skin nodules that were
      quiescent for 10 years. Then the course of the disease suddenly changed and
      progressed rapidly. She had systemic chemotherapy and initially had a complete
      response, but she relapsed within 1 month of completion of chemotherapy. She then
      had partial response with further chemotherapy but relapsed rapidly. She died
      within 15 months of her lymphoma changing to its aggressive form. These cases
      illustrate the often poor prognosis of cutaneous CD56 positive lymphomas.

PMID- 15870870
TI  - Apoptosis induced by 5-fluorouracil, cisplatin and paclitaxel are associated with
      p53 gene status in gastric cancer cell lines.
AB  - In a recent study, we evaluated the efficacy and toxicity of 5-fluorouracil (5
      FU), cisplatin (CDDP), and 5-FU plus CDDP (FP treatment) in gastric cancer cell
      lines and examined the relationship between the response to FP treatment and
      apoptosis. Our study indicated that there may be prognostic value in measuring
      p53 prior to FP treatment, and that cancers with wild-type p53 may be better
      candidates for FP treatment than those with mutant-type p53 in gastric cancer
      patients. In the present study, because cells with mutant-type p53 are suggested
      to be less responsive to FP chemotherapy treatment, we examined the relationship
      between the response to paclitaxel and apoptosis in MKN45 and MKN28 human gastric
      cancer cell lines by flow cytometry. In both MKN45 and MKN28 cells, paclitaxel
      arrested cells in the G2/M phases of the cell cycle after 24 h. Additionally, in
      both MKN45 and MKN28 cells, paclitaxel produced a significant rise in the number
      of subG1-phase cells after 72 h by the flow cytometry histogram. From these
      results, our previous study suggests that cells with mutant-type p53 may be less
      responsive to FP treatment and the present study indicates that another anti
      cancer drug like paclitaxel, which might be mediated by a p53-independent
      pathway, should be selected. These insights may provide a new strategy for
      gastric cancer chemotherapy, especially second-line chemotherapy or adjuvant
      chemotherapy.

PMID- 15870871
TI  - Modulation of sensitivity to doxorubicin by the histone deacetylase inhibitor
      sodium butyrate in breast cancer cells.
AB  - The histone deacetylase inhibitor sodium butyrate induces several gene products
      that modify cellular metabolism. Here, we investigated its ability to modulate
      glutathione-related detoxification enzymes in the breast cancer cell line MCF-7
      and a derivative resistant to vincristine (VCREMS). We found that sodium butyrate
      induced glutathione S-transferase and glutathione-dependent peroxidase activities
      and triggered glutathione depletion. Expression of MRP1, an ATP-dependent GS-X
      pump, was unmodified. Moreover, isobologram analysis showed that sodium butyrate
      sensitized VCREMS to doxorubicin-mediated toxicity. Verapamil, an inhibitor of
      MRP1, did not significantly affect this chemosensitizing effect, suggesting that
      the observed toxicity stems from multifactorial mechanisms. Interestingly,
      synergism between sodium butyrate and doxorubicin was more pronounced in
      resistant VCREMS cells than in parental sensitive MCF-7 cells.

PMID- 15870872
TI  - Apoptosis and differentiation induced by staurosporine in granulosa tumor cells
      is coupled with activation of JNK and suppression of p38 MAPK.
AB  - We report here that staurosporine can induce apoptosis or differentiation of
      granulosa tumor cells depending on its dosage. In presence of staurosporine
      concentrations > 50 nM, apoptosis was triggered in human granulosa cell tumor
      cells COV434. In the presence of concentrations < 50 nM, the shape of the
      otherwise globular granulosa cells differentiated into a flattened epithelioid
      like appearance. The process was associated by the induction of prostaglandin
      synthase-2 (PGS-2) and C/EBPbeta expression and by an increase in progesterone
      production in the supernatant culture medium. The observed effects of
      staurosporine were synergized by forskolin. With phosphorylation-specific Western
      blotting and protein kinase assays, it was demonstrated that staurosporine
      suppresses the phosphorylation of p38 and activates JNK. These results suggest
      that p38MAPK and JNK signal transduction pathways were involved in the regulation
      of granulosa cell differentiation by staurosporine. These results may indicate
      the usefulness of staurosporine or its analogs for the development of a future
      medical treatment of granulosa tumors.

PMID- 15870873
TI  - Clinical effects of a chimeric anti-EpCAM monoclonal antibody in combination with
      granulocyte-macrophage colony-stimulating factor in patients with metastatic
      colorectal carcinoma.
AB  - The EpCAM antigen is highly expressed on colorectal carcinoma (CRC) cells. Murine
      anti-EpCAM MAb (anti-EpCAM mMAb) alone or in combination with cytokines may
      induce clinical responses including long-lasting complete remissions (CR) in
      patients with metastatic disease. The chimeric variant of anti-EpCAM MAb (anti
      EpCAM cMAb) interacts more efficiently with human effector cells (ADCC) than the
      murine counterpart in the killing of colorectal carcinoma cells in vitro, an
      important mechanism of action for antibody in vivo. Granulocyte-macrophage colony
      stimulating factor (GM-CSF) augments immune effector cell functions in vivo and
      may enhance the therapeutic effect of MAbs. In this study, the therapeutic
      efficacy of the combination of anti-EpCAM cMAb and GM-CSF was evaluated in 24
      patients with metastatic CRC. GM-CSF was given s.c. once daily for 10 consecutive
      days and on day 3, anti-EpCAM cMAb was given i.v. A treatment cycle was repeated
      every 4th week. Five patients achieved stable disease > 3 months (overall
      response rate 21%). Responding patients survived significantly longer than non
      responding patients (p = 0.030). The frequency of patients with an immediate-type
      allergic reaction (ITAR) against anti-EpCAM cMAb at the 1st, 2nd, 3rd and 4th
      treatment cycles was as 13%, 29%, 25% and 19% respectively. Compared to a
      previous study where anti-EpCAM mMAb was used in a similar treatment regimen, the
      present protocol did not augment the overall or progression-free survival. The
      overall response rate was also similar to anti-EpCAM mMAb treated patients (6/22,
      27%), but the anti-EpCAM mMAb treatment protocol induced two CR, one MR and three
      SD. Further studies are warranted to establish the role of EpCAM as a target for
      antibody therapy, specifically the significance of chimeric or humanized anti
      EpCAM MAbs.

PMID- 15870874
TI  - Identification of a Mu-9 (anti-colon-specific antigen-p)-reactive peptide having
      homology to CA125 (MUC16).
AB  - Mu-9, an anti-colon specific antigen-p (CSAp) monoclonal antibody (MAb), has
      shown excellent gastrointestinal cancer targeting in both pre-clinical and
      clinical trials. With the recent development of the humanized version of this
      MAb, Mu-9 will receive further attention as a potential therapeutic agent for
      colorectal cancer. Hence, we have undertaken studies to examine the nature of the
      CSAp antigen and the structure of the Mu-9 epitope. M13 phage displaying random
      12-mer peptides were used to isolate a peptide that binds both murine and
      humanized Mu-9 MAbs. The peptide, Mu-9-p16, was synthesized and found to inhibit
      binding of Mu-9 to CSAp with a Ka for the humanized antibody of 4.28 x 10(-7) +/-
      0.91 x 10(-7) M. Control peptides did not bind Mu-9, nor did they inhibit the Mu
      9-CSAp interaction. Three overlapping peptides were synthesized and used to
      demonstrate that the last six residues were sufficient to inhibit the Mu-9-CSAp
      interaction. A search of GenBank revealed that the peptide sequence IHPRP, was
      also present within CA125, a very high molecular weight ovarian cancer-associated
      antigen. The sequence is present outside of the known antigenic regions
      identified by the Oc125, M-11 and Ov197 anti-CA125 antibodies. To demonstrate
      that CSAp and CA125 may be the same protein, a heterologous sandwich enzyme
      immunoassay was developed with anti-CA125 MAbs used as capture reagents and Mu-9
      as probe. By use of this ELISA system, we were able to specifically identify
      CSAp. In conclusion, our results indicate that the Mu-9-p16 peptide isolated
      through our screen identifies a peptide epitope shared by CSAp and CA125 and
      suggest that these proteins are related.

PMID- 15870875
TI  - Curcumin decreases cell proliferation rates through BTG2-mediated cyclin D1 down
      regulation in U937 cells.
AB  - Curcumin is a promising chemopreventive agent due to its multiple properties
      including anti-inflammation, induction of apoptosis and inhibition of signal
      cascades involving cell proliferation. It has been reported that curcumin-treated
      cells show decreased expression of cyclin D1, ultimately resulting in decreased
      cell growth rate. Thus, modulation of cell cycle regulatory proteins by curcumin
      has been suggested as one of the important mechanisms underlying its
      chemopreventive effects. However, the precise molecular mechanisms involving down
      regulation of cyclin D1 by curcumin are not largely understood. In this study we
      investigated the mechanisms of cyclin D1 down-regulation by curcumin in U937
      cells. Expressions of cyclin D1, particularly at protein and mRNA levels, were
      clearly decreased in curcumin-treated cells. The stability of cyclin D1 mRNA was
      not affected by curcumin treatment. Treatment of curcumin increased expression of
      BTG2 mRNA, a member of anti-proliferative gene family and a negative
      transcriptional regulator of cyclin D1. Furthermore, overexpression of BTG2 led
      to down-regulation of cyclin D1 mRNA expression in U937 cells. Nuclear
      translocation of p65 NF-kappaB is involved in the expression of cyclin D1 mRNA.
      Treatment of curcumin inhibited nuclear translocation of p65 NF-kappaB. Moreover,
      the expression of cyclin D1 mRNA was dramatically decreased after co-treatment
      curcumin with NF-kappaB inhibitors. The data presented here indicate that
      curcumin-induced down-regulation of cyclin D1 mRNA is mediated by induction of
      BTG2 as well as inhibition of nuclear translocation of NF-kappaB.

PMID- 15870876
TI  - Immunological evaluation of vaccination of peptides derived from epithelial
      cancer-related antigens in two patients with hematological malignancy.
AB  - Recent advances in tumor immunology have resulted in identification of many
      epithelial cancer-related antigens and peptides applicable to specific
      immunotherapy. We and others have reported that several epithelial cancer-related
      antigens are also expressed in hematological malignancies. Two patients with
      hematological malignancy (multiple myeloma and chronic lymphocytic leukemia) were
      vaccinated with peptides derived from epithelial cancer-related antigens to
      evaluate the immune responses to peptides under a personalized peptide
      vaccination regimen. There was no adverse event except for local skin reaction at
      the injection site. The peptide vaccination augmented both peptide-specific CTLs
      cytotoxic to hematological malignant cells in post-vaccination peripheral blood
      mononuclear cells and peptide-specific IgG in post-vaccination sera. A transient
      but obvious decrease of malignant cells was observed at the early phase of the
      vaccination in both cases. Vaccines consisting of peptides derived from
      epithelial cancer antigens safely increased anti-tumor cell activity in patients
      with hematological malignancies. These results may provide a scientific rationale
      in use of epithelial cancer-related antigens for specific immunotherapy to
      patients with hematological malignancies.

PMID- 15870877
TI  - Anti-angiogenic and anti-tumor apoptotic activities of a topoisomerase II
      inhibiting agent SJ-8026.
AB  - A new piperazine derivative, SJ-8026, is a synthetic anti-cancer agent which
      exhibits topoisomerase II-inhibiting activities. In this study, we investigated
      the possibility that this compound inhibits angiogenesis and induces tumor-cell
      apoptosis using bovine aortic endothelial cells (BAECs) and human hepatocellular
      carcinoma cells (HepG2) as a model system. in vivo, SJ-8026 decreased the
      neovascularization of chick embryos and the basic fibroblast growth factor
      induced angiogenesis in the chorioallantoic membrane and the mouse Matrigel
      implants. in vitro, SJ-8026 treatment resulted in the inhibition of
      proliferation, migration, invasion and tube formation in BAECs. In addition, the
      treatment of SJ-8026 in HepG2 cells reduced the cell viability, and caused the
      production of fragmented DNA and the morphological changes corresponding to
      apoptosis including condensed and fragmented DNA. SJ-8026 also elicited the
      release of cytochrome c and the activation of caspase-3. Therefore, it is
      possible that SJ-8026 functions as both angiogenesis inhibitor and apoptosis
      inducer. Taken together, these results suggest that SJ-8026 may be a candidate
      for strong anti-cancer agent with the ability to inhibit the angiogenesis of
      endothelial cells and to induce the apoptosis of tumor cells.

PMID- 15870878
TI  - Identification of novel variant, 1484delG in the 3'UTR of H3F3B, a member of the
      histone 3B replacement family, in ovarian tumors.
AB  - Previous studies have implicated the chromosomal region at 17q25 as harboring
      tumor suppressor genes based on the frequent loss of heterozygosity (LOH)
      observed in epithelial ovarian cancers (EOC). RT-PCR validation of Affymetrix
      GeneChip expression of H3F3B, a member of the 3B histone family that maps to
      17q25.1, revealed a doublet band in cDNA from one of four EOC cell lines, OV90.
      In contrast to three other EOC cell lines (TOV81D, TOV112D and TOV21G) and
      primary cultures derived from normal ovarian surface epithelial cells (NOSE),
      sequence analysis of the cDNA revealed a deletion of G at position 1484 of the
      transcribed sequence which is located within the 3'UTR of H3F3B. OV90 was derived
      from ascites fluid of an undifferentiated adenocarcinoma of ovarian origin. The
      variant allele was identified in 1 of 65 (2%) healthy women with no prior history
      of cancer and in 5 participants with ovarian tumors comprising of 4 of 79 (5%)
      malignant EOC, none of 10 low malignancy potential tumors, and 1 of 8 (13%)
      benign tumors. All carriers of the variant alleles were heterozygous and tumor
      samples did not exhibit preferential LOH of the normal allele. The variant allele
      was identified in EOC samples of clear cell (1 of 20), mucinous (1 of 8), mixed
      cell (1 of 3) and undifferentiated (1 of 2) histopathological subtypes but none
      of 34 serous or 12 endometrioid subtype tumors. One of 3 mucinous benign tumors
      also harbored the variant allele. The functional significance of the variant is
      unknown, however its presence in rare subtypes of ovarian epithelial tumors
      warrants further investigation.

PMID- 15870879
TI  - Expression of vasoactive intestinal peptide and functional VIP receptors in human
      prostate cancer: antagonistic action of a growth-hormone-releasing hormone
      analog.
AB  - Vasoactive intestinal peptide (VIP) functions as a mitogenic agent in the human
      prostate gland acting by autocrine/paracrine mechanisms. Here we extend knowledge
      on the VIP system (expression of VIP and VIP receptors, functionality of VIP
      receptors) at this level by analyzing the differences between human normal
      prostate and prostate carcinoma specimens. RT-PCR showed the expression of mRNA
      for VIP in normal and malignant tissues, whereas VIP levels, as measured by
      enzyme immuno-analysis, were about two times higher in adenocarcinoma samples.
      Real-time RT-PCR indicated a minor expression of VPAC2 receptors in the prostate
      gland, as well as the overexpression of VPAC1 and PAC1 receptors in malignant
      tissue specimens. Radio-labeled binding experiments with [125I]VIP showed an
      increased number of VIP binding sites (2.5 times for the high- and 1.7 times for
      the low-affinity sites) during malignant transformation, whereas the affinity
      values were unaffected. The receptors were functional in control and cancer
      tissues as shown by the ability of increasing VIP doses to stimulate adenylate
      cyclase activity. Interestingly, JV-1-53 (a GHRH-related peptide analog) (at 0.1
      microM) behaved as a potent VIP antagonist since it inhibited by 60% the maximal
      VIP effect upon the enzyme activity. The results further explain the mechanisms
      of the autocrine/paracrine actions of VIP in human prostate and prostatic
      carcinoma through the observation of differences between healthy tissue and
      malignant transformation. Moreover, present data support the potential usefulness
      of VIP and/or synthetic peptide analogs for diagnostic or radiotherapeutic
      purposes as well as for long-term peptide therapy in this malignancy.

PMID- 15870880
TI  - Modulation of Raf/MEK/ERK kinase activity does not affect the chemoresistance
      profile of advanced prostate cancer cells.
AB  - The Raf/MEK/ERK signaling cascade has been extensively studied for its roles in
      growth and differentiation of a variety of cell types. Confliciting evidence
      exists regarding the function of classical MAPK signaling with regards to the
      development of chemotherapeutic drug resistance; some reports describe an pro
      survival role, whereas others have suggested that activation of Raf/MEK/ERK is
      essential for drug-induced death. To elucidate the importance of MAPK signaling
      in the development of advanced prostate cancer drug resistance, DU145 and PC3
      prostate cells were stably-infected/transfected with constitutively-activated
      mutants of both Raf-1 and B-Raf. Results from MTT analyses suggested that
      activation of either Raf-1 or B-Raf is inconsequential in prostate cancer
      chemoresistance. To confirm these findings, the MAPK signal transduction cascade
      was activated with EGF and response to doxorubicin or paclitaxel was measured in
      the presence/absence of the MEK-specific inhibitor, U0126. These results showed
      that inhibition of signals transduced by the MAPK pathway are insufficient to
      affect the chemoresistance profile of advanced prostate cancer cells. Together,
      these data demonstrate that the response of prostatic tumors to the
      chemotherapeutic compounds doxorubicin and paclitaxel is independent of
      Raf/MEK/ERK signaling.

PMID- 15870881
TI  - Expression and activation of apoptosis-related molecules involved in interferon
      alpha-mediated apoptosis in human liver cancer cells.
AB  - Interferon (IFN)-alpha directly inhibits proliferation of liver cancer cells by
      inducing apoptosis, but the molecular mechanisms by which IFN-alpha induces
      apoptosis in these cells are not fully understood. We examined the effect of
      broad spectrum caspase inhibitor, Z-VAD-fmk, and the caspase activation in IFN
      alpha-mediated apoptosis by using 4 liver cancer cell lines that were sensitive
      or resistant to IFN-alpha-mediated apoptosis. Involvement of apoptosis-related
      mitochondrial proteins and Bcl-2 family proteins in IFN-alpha-mediated apoptosis
      was further examined in 1 sensitive cell line (KIM-1). The Z-VAD-fmk completely
      or moderately inhibited IFN-alpha-mediated apoptosis in the sensitive cells. IFN
      alpha induced time-dependent activation of caspase-3 in the sensitive cells,
      while the resistant cells showed mild or no activation. Activation of caspase-9,
      caspase-8, and caspase-7, and the cleavage of poly(ADP-ribose)polymerase were
      identified in either or both of the sensitive cell lines, but not in the
      resistant cells. In KIM-1 cells, the release of cytochrome c and Smac/DIABLO from
      mitochondria to cytosole was confirmed. Meanwhile, Bcl-xL was upregulated, and
      Bid activation or translocation, or conformational changes of Bax were not
      identified. In conclusion, our results suggest IFN-alpha-mediated apoptosis in
      liver cancer cells involves the mitochondrial apoptotic pathway and is induced by
      activating various caspases.

PMID- 15870882
TI  - Deficient MGMT and proficient hMLH1 expression renders gallbladder carcinoma
      cells sensitive to alkylating agents through G2-M cell cycle arrest.
AB  - The aim of this study was to assess whether combined evaluation of O6
      methylguanine methyltransferase (MGMT) and hMLH1 status determines sensitivity to
      monofuntional alkylating agents such as N-methyl-N-nitrosourea (MNU) and
      dacarbazine (DTIC) against gallbladder carcinoma cells. The molecular mechanism
      behind MGMT and hMLH1 status affecting the cell cycle was also addressed. Using 5
      gallbladder cancer carcinoma lines and 1 colon carcinoma cell line (SW48), MGMT
      and hMLH1 expression was analyzed using RT-PCR and Western blotting. MGMT and
      hMLH1 status in the 6 cell lines was compared with drug sensitivity to MNU. As a
      result, cell lines that were MGMT-/hMLH1+ had the highest sensitivity to MNU,
      compared with MGMT+/hMLH1+ and MGMT-/hMLH1- cells. In flow cytometric analysis,
      G2-M cell cycle arrest was specifically observed in GB-d1 cells with MGMT-/hMLH1+
      and expression of cyclin A and Cdc2 in GB-d1 cells was significantly reduced by
      MNU treatment, but not observed in KMG-C cells with MGMT+/hMLH1+. Finally, we
      assessed the in vitro and in vivo effect of the clinically used alkylating agent
      DTIC in these cells. The highest sensitivity to DTIC was also observed in MGMT
      /hMLH1+. In conclusion, MNU suppressed cell proliferation of MGMT-/hMLH1+
      gallbladder carcinoma cells by arresting the cell cycle at the G2-M phase,
      accompanied by down-regulation of cyclin A and Cdc2. These results indicated that
      expression of MGMT and hMLH1 could be used to select candidates for alkylating
      agent chemotherapy against gallbladder carcinoma.

PMID- 15870883
TI  - Skeletal muscle wasting in tumor-bearing rats is associated with MyoD down
      regulation.
AB  - Cachexia is a syndrome characterized by profound skeletal muscle wasting that
      frequently complicates malignancies. A number of studies indicate that protein
      hypercatabolism, largely mediated by classical hormones and cytokines, is the
      major component of muscle depletion. Impaired regeneration has been suggested to
      contribute to the reduction of muscle size. In particular, it has been shown that
      the expression of MyoD, a muscle-specific transcription factor, is down-regulated
      by cytokines such as TNFalpha and IFNgamma in a NF-kappaB-dependent
      posttranscriptional manner. The present study investigated whether modulations of
      the transcription factor MyoD are associated with the onset of muscle wasting in
      a well established model of cancer cachexia. Rats bearing the Yoshida AH-130
      hepatoma develop a condition of muscle protein hypercatabolism, largely dependent
      on TNFalpha bioactivity. In the gastrocnemius of these animals the expression of
      MyoD was markedly reduced, paralleling the decrease of muscle weight. This
      pattern is associated with increased nuclear translocation of AP-1, while DNA
      binding assays did not detect any change in NF-kappaB activity. This is the first
      observation demonstrating that muscle depletion in tumor-bearing rats is
      associated with a down-regulation of MyoD levels. Although the underlying
      mechanisms remain to be clarified, this change is compatible with the hypothesis
      that a reduced expression of molecules involved in the regulation of the
      regenerative response may concur to muscle wasting in cancer cachexia.

PMID- 15870884
TI  - Extracellular signal-regulated kinase and AP-1 pathways are involved in reactive
      oxygen species-induced urokinase plasminogen activator receptor expression in
      human gastric cancer cells.
AB  - Overexpression of urokinase plasminogen activator receptor (uPAR) is known to
      correlate closely with tumor cell invasion and metastasis. In gastric cancer,
      however, the mechanism for induction of uPAR remains to be elucidated. In this
      study, to investigate the effect of reactive oxygen species (ROS) on uPAR
      expression and the underlying signal pathways in human gastric cancer AGS cells,
      phenazine methosulfate (PMS) and H2O2 were used as ROS generator. PMS and H2O2
      induced the uPAR expression in time- and concentration-dependent manner. PMS and
      H2O2 also induced the activation of extracellular signal-regulated kinases (Erk)
      1/2. A specific inhibitor of MEK-1 (PD980590) was found to suppress the PMS
      induced uPAR expression and the uPAR promoter activity. Expression of vectors
      encoding a mutated-type MEK-1 resulted in decreases in the uPAR promoter
      activity. Electrophoretic mobility shift assay revealed that PMS increased time
      dependently the DNA binding activity of AP-1. Transient transfection studies
      using AP-1 decoy confirmed that the activation of AP-1 is involved in PMS-induced
      uPAR upregulation. The AGS cells pretreated with PMS showed a remarkably enhanced
      invasiveness and this effect was partially abrogated by uPAR neutralizing
      antibodies. The above results suggest that ROS induces uPAR expression via Erk
      1/2 and AP-1 signaling pathways and, in turn, stimulates the cell invasiveness in
      human gastric cancer AGS cells.

PMID- 15870885
TI  - Reconstitution of caspase-3 sensitizes MCF-7 breast cancer cells to radiation
      therapy.
AB  - Caspase-3 plays an important role in apoptotic execution. Caspase-3 deficiency or
      down-regulation has been reported in breast and other kinds of cancers. Given the
      redundancy of caspase cascade, however, the impact of caspase-3 deficiency/down
      regulation on radiation-induced apoptosis remains to be defined. In this report,
      the specific role of caspase-3 in radiotherapy-induced apoptosis was studied
      using MCF-7 control (MCF-7/pv, caspase-3 deficient) and caspase-3 reconstituted
      MCF-7 (MCF-7/c3) breast cancer cells. Caspase-3 reconstitution significantly
      enhanced radiation-induced apoptosis, with a decrease in the survival fraction,
      an increase in caspase activation, cleavage of cellular death substrates and
      mitochondrial depolarization. We also found that the activation of caspase-7 was
      caspase-3-dependent in radiation-induced apoptosis, which suggests a mini-cascade
      among the effector caspases and that caspase-3 is essential for signal
      amplification. In comparing the patterns of death substrates cleavage in
      radiation-induced apoptosis with that in doxorubicin and TNF-alpha-induced
      apoptosis, we found that cleavage of lamin B and beta-actin was relatively more
      susceptible to radiation, which is enhanced in the presence of caspase-3,
      suggesting cytoskeleton proteins might be preferred markers for radiation-induced
      apoptosis. These data indicate that caspase-3 plays a critical role in
      radiotherapy-induced apoptosis, and suggest that caspase-3 deficiency may
      contribute to the radioresistance of breast cancers.

PMID- 15870886
TI  - WWOX mRNA expression profile in epithelial ovarian cancer supports the role of
      WWOX variant 1 as a tumour suppressor, although the role of variant 4 remains
      unclear.
AB  - WWOX is a candidate tumour suppressor gene that exhibits LOH or homozygous
      deletion in several tumour types. As well as the predominant full-length
      transcript (variant 1) there also exist alternatively spliced transcripts found
      previously only in malignant tissue. It has been suggested that proteins encoded
      by these variants may interfere with normal WWOX function in a dominant negative
      fashion. The most prevalent alternate transcript demonstrated in ovarian cancer
      is variant 4, which lacks exons 6-8. Here, we report the first comparison of the
      mRNA expression of WWOX variants 1 and 4 in human ovarian tumours and normal
      ovaries, and correlate expression with clinical data. We demonstrate
      significantly lower WWOX variant 1 expression in tumours than in normal ovaries.
      This reduction was not associated with any specific clinical subgroup. Variant 4
      was expressed at low levels, and significantly associated with high grade and
      advanced stage ovarian cancer. Furthermore, tumours co-expressing variant 4 and
      relatively high levels of variant 1 showed significantly worse survival than
      tumours expressing variant 1 alone. However, variant 4 was also frequently
      identified in non-malignant ovarian tissue. These results support the role of
      WWOX variant 1 as a suppressor of ovarian tumourigenesis, but the role of variant
      4 remains speculative.

PMID- 15870888
TI  - Differential expression analysis of MIM (MTSS1) splice variants and a functional
      role of MIM in prostate cancer cell biology.
AB  - We previously identified MIM-A (missing in metastasis, MTSS1) by differential
      display techniques as missing in invasive, metastatic bladder cancer cell lines
      and suggested that MIM-A is a novel putative metastasis suppressor gene.
      Characterization of the MIM gene revealed a WH2 (Wiskott-Aldrich syndrome protein
      homology 2) domain in the C-terminus that is known to bind actin monomers and
      regulate organization of the actin cytoskeleton. Here, we further describe two
      alternatively splice variants of MIM-A, called MIM(12del) and MIM-B, which share
      > 50% amino acid sequence homology with MIM-A in the C-terminal domain. We show
      that expression of all three transcripts is down-regulated in prostate cancer
      cell lines and tumor samples from patients. In addition, we generated stably
      transfected PC-3 cells overexpressing MIM-A to evaluate the importance of MIM-A
      in prostate cancer biology. The initial experiments show that expression of MIM
      decreased the number of actin filaments and was associated with a decrease in the
      G:F actin ratio. Overexpression of MIM-A had no effect on PC-3 cell adhesion to
      extracellular matrices, as well as no effect on PC-3 motility. Further,
      overexpression of MIM-A reduced the rate of PC-3 cell proliferation. These
      results support the hypothesis that MIM-A is an actin-binding protein and
      implicate a role of MIM-A in the regulation of cellular proliferation. These data
      suggest that the reduction of MIM-A gene expression in prostate cancer and other
      cancers may contribute to tumor growth and development, as well as metastasis.

PMID- 15870887
TI  - Enhancing the photodynamic effect of hypericin in tumour spheroids by
      fractionated light delivery in combination with hyperoxygenation.
AB  - The aim of this study was to explore the hypothesis of oxygen depletion during
      light irradiation as a possible explanation for the incomplete response seen
      after hypericin-mediated photodynamic therapy (PDT) under specific conditions. To
      investigate this, we performed PDT experiments using transitional cell carcinoma
      spheroids with fractionated light irradiation and hyperoxygenation. After 2-h
      incubation with 3 different hypericin concentrations, spheroids were irradiated
      either continuously or with fractionated light delivery. The effect of
      hyperoxygenation was investigated by bubbling normobaric oxygen in the solution
      surrounding the spheroids before continuous irradiation or during the dark
      interval of light fractionation. The PDT efficacy was evaluated with an MTT
      antiproliferation assay and apoptotic cells were visualized after PDT by DAPI
      staining. Our results show that fractionated light delivery with dark intervals
      ranging from 1 to 10 min does not enhance the PDT efficacy in spheroids at all,
      whereas hyperoxygenation, using appropriate hypericin concentrations and
      oxygenation intervals, results in a virtually complete malignant cell killing
      through apoptosis. This study suggests that oxygen depletion is the major source
      of relative treatment failure in hypericin-mediated PDT with spheroids, which can
      only be overcome with hyperoxygenation. Therefore, whole bladder wall PDT with
      hypericin is likely to become a very efficient antitumoural treatment against
      superficial bladder cancer, on the condition that instillation fluids are
      hyperoxygenated during light irradiation.

PMID- 15870889
TI  - Are telomeres a specific target for mutagenic attack by cytostatics in neoplastic
      cells?
AB  - Damage to telomeres induced by cytostatic therapy theoretically could generate
      telomere shortening and, subsequently, induce an additional genomic instability
      in neoplastic cells. Model experiments were carried out to examine this
      hypothesis. Cells of the T-ALL derived cell line CCRF-CEM were exposed to various
      different concentrations of Bleomycin (BLM) or Mitomycin C (MMC) for various
      times. Telomere lengths of metaphase chromosomes of the exposed cells were
      compared with those without this exposure (controls). In addition, telomerase
      activity was determined with a TRAP assay under the given conditions using the
      BLM experiments as a model. Although slight changes of total telomere length
      could be found in single experiments, the differences between exposed and non
      exposed cells were not significant. Also, a considerable telomerase activity was
      shown which, however, did not substantially differ between exposed and non
      exposed cells. From these data it may be concluded that, at least in the examined
      cell line, telomeres are not a preferential target for this kind of mutagenic
      attack.

PMID- 15870890
TI  - Comparative genomics on nemo-like kinase gene.
AB  - WNT signals are transduced to the planar cell polarity (PCP) pathway or the beta
      catenin pathway. Drosophila Frizzled (Fz), Starry night (Stan), Van Gogh (Vang),
      Dishevelled (Dsh), Prickle (Pk), Diego (Dgo) and Nemo (Nmo) are implicated in the
      PCP signaling pathway. Choi and Benzer identified Drosophila Nmo in 1994, and
      Brott et al identified mouse Nemo-like kinase (Nlk) in 1998. Nlk positively
      regulates the PCP pathway, and negatively regulates the beta-catenin pathway.
      Here, we identified and characterized rat Nlk gene, Nlk2 gene and Nlkp pseudogene
      by using bioinformatics. Nlk gene, consisting of 11 exons, was mapped to rat
      chromosome 10q25. Rat Nlk gene encoded 515-aa Nlk protein with the
      serine/threonine kinase domain, poly(His) tracts and poly(Ala) tract, which
      showed 100, 99.8, 97.1 and 89.5% total-amino-acid identity with mouse Nlk, human
      NLK, Xenopus nlk and zebrafish nlk, respectively. Rat Nlk2 gene and Nlkp
      pseudogene were mapped to rat chromosome 13p13 and 2q44, respectively. Nlk2 gene
      and Nlkp pseudogene, consisting of a single exon, were not evolutionarily
      conserved. Nlk2 gene and Nlkp pseudogene were predicted as retrotransposed Nlk
      homologs within the rat genome. Nlk2 gene encoded a 480-aa Nlk2 protein with
      partial deletion within the kinase domain, which was predicted as the dominant
      negative Nlk homolog. This is the first report on the Nlk gene and
      retrotransposed Nlk homologs within the rat genome.

PMID- 15870891
TI  - Tissue engineering with adult stem cells in reconstructive surgery (review).
AB  - Tissue engineering is a multidisciplinary field combining biology and engineering
      along with clinical application to design, manufacture, modify, grow and maintain
      living tissue. This field has enjoyed tremendous growth in the past 10 years
      fueled by its potential role in regenerating new tissues and naturally healing
      injured or diseased organs. Many approaches to tissue engineering have been
      explored, including ex vivo de novo construction of tissues and strategies of in
      vivo induction of tissue regeneration. Interventions are hindered by factors such
      as rejection by the immune system, limited blood supply or morbidity of the donor
      site. Regardless of the approach, most researchers and clinicians agree that any
      successful tissue engineering construct will derive from a single unit, the cell.
      Because the engineering of tissue necessitates a sufficient number of tissue
      specific cells with minimal donor site morbidity, a great deal of scientific
      effort has been directed towards stem cell research and the use of stem cells as
      a source of cells for new tissues. This review aims at outlining the role of stem
      cells in tissue engineering, focusing on the use of adult-derived stem cells as
      applied to the research and practice of plastic surgery.

PMID- 15870892
TI  - Influence of glucose and inflammatory cytokines on TGF-beta1 and CTGF mRNA
      expressions in human peritoneal mesothelial cells.
AB  - Peritoneal fibrosis is a major complication of long-term continuous ambulatory
      peritoneal dialysis (CAPD) treatment. Transforming growth factor-beta (TGF-beta)
      has been reported to play an important role in the fibrosis of various tissues by
      stimulating connective tissue growth factor (CTGF) expression. In order to
      elucidate the mechanism of CAPD-related peritoneal fibrosis, we studied the
      influence of high glucose concentrations and inflammatory cytokines on mRNA
      expressions of TGF-beta and CTGF in cultured human peritoneal mesothelial cells
      (HPMC). HPMC were isolated from normal omentum and cultured with 0.5 or 1.0%
      glucose or mannitol for 7 days. TGF-beta1 and CTGF mRNA were quantified by one
      step real-time reverse transcription-polymerase chain reaction (real-time RT
      PCR). TGF-beta1 and CTGF mRNA expression levels were significantly increased
      (p<0.05) by glucose in a dose-dependent manner, but not by mannitol. The
      expression levels were correlated between TGF-beta1 and CTGF. Effects of
      inflammatory cytokines were also examined by adding tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1 (IL-1) or interleukin-6 (IL-6) to the medium at 0.1
      ng/ml for 2 days. TGF-beta1 expression tended to be increased by TNF-alpha and IL
      6. On the other hand, CTGF expression was significantly decreased (p<0.01) by IL
      1 but not changed by TNF-alpha or IL-6. These results suggest that high glucose
      concentration may play a central role in peritoneal fibrosis. Responses of TGF
      beta1 and CTGF to inflammatory cytokines were not necessarily identical,
      suggesting that CTGF may be a better therapeutic target for peritoneal fibrosis
      than TGF-beta1.

PMID- 15870893
TI  - Separation of white blood cells from erythrocytes on a dielectrophoresis (DEP)
      based 'Lab-on-a-chip' device.
AB  - The 'Lab-on-a-chip technology' involves miniaturization of complex analytical
      procedures and is expected to enable laboratory testing to move from the central
      laboratory employing complex equipment into non-laboratory settings. We report
      the application of a printed circuit board (PCB)-based chip, generating
      dielectrophoretic (DEP)-based cylinder-shaped cages for separation and recovery
      of white blood cells from erythrocytes. This possibility is of interest to
      develop low-cost Lab-on-a-chip devices for diagnostic purposes. Accordingly, we
      demonstrate that white blood cells recovered from this Lab-on-a-chip device are
      suitable for PCR-based molecular diagnosis procedures employing DNA sequencing or
      biospecific interaction analysis using surface plasmon resonance and biosensor
      technology.

PMID- 15870894
TI  - Expression of neurotransmitters and neurotrophins in human adenoid tissue.
AB  - Mucosae-associated lymphoid tissues are richly innervated and the mucosae contain
      peptidergic nerve endings associated with different types of cells and
      macrophages. The lymphatic tissue is known to interact with the nervous system
      and several organs, implicated in the host response to a wide range of stressors,
      and is also richly innervated. We focussed our attention on the immune organs
      with particular regard to the human adenoid lymphatic tissues in order to
      investigate the neuroimmune links and the possible existence of relationships
      among different neurotransmitters and lymphocytes, macrophages, epithelial cells
      and nerve fibers by testing the expression of certain neurotransmitters and
      neurotrophins (NTs) with their own receptors.

PMID- 15870895
TI  - Effects of beta-amyloid on rat neuromicrovascular endothelial cells cultured in
      vitro.
AB  - Several studies have shown that beta-amyloid (beta A) deposits are associated
      with damage of cerebral vessels and that in Alzheimer's disease (AD) beta A
      peptides are cytotoxic for cerebral endothelial cells (ECs). However, little is
      known about the mechanisms underlying these effects of beta A peptides. Hence, we
      have investigated the effects of beta A(1-40) and beta A(1-42) on rat
      neuromicrovascular ECs (NECs) cultured in vitro. NECs were isolated, plated
      (1.5x10(4) cells/cm2) on collagen/fibronectin-coated Petri dishes and cultured in
      EC growth medium MV2. After 24 h of culture, NECs were incubated with beta A(1
      40) and beta A(1-42) (10(-9) or 10(-7) M) and cultured for another 3, 24 or 48 h.
      Cell viability was assayed by either trypan blue exclusion or by measuring redox
      activity (MTS assay). Cell proliferation was assessed by measuring the
      incorporation of 5'-bromo-2'-deoxyuridine into DNA, cell apoptosis by TUNEL assay
      and cell necrosis by evaluating the release of lactate dehydrogenase. The
      morphology of cultured NECs was examined by transmission electron microscopy.
      Other NECs were plated (2.5x10(4) cells/cm2) on Matrigel coated-wells and
      incubated for 18 h in the presence or absence of beta A peptides for in vitro
      angiogenesis assay. Beta A peptides significantly decreased NEC viability and
      enhanced cell apoptosis and necrosis rates. NEC proliferation was not
      significantly affected. The effects were seen after an incubation period of 3 h
      (and also 24 h in the case of the redox activity) but not 48 h and beta A(1-42)
      was much more effective in its toxic effects than beta A(1-40). NECs incubated
      for 24 h with beta A peptides displayed ultrastructural signs of cell
      degeneration. beta A peptides prevented NECs cultured on Matrigel to form a
      capillary-like network and image analysis showed that the downloading of
      dimensional and topological parameters of the meshwork was significant only in
      the case of the incubation with beta A(1-42). Collectively our findings allow us
      to conclude that i) beta A peptides exert a marked toxic effect on cultured NECs,
      which conceivably reduces their in vitro angiogenic activity; ii) beta A(1-42) is
      the more toxic form, which could suggest its main role in the pathogenesis of
      cerebral vessel lesions in AD and iii) the maximum toxic action occurs after a
      short incubation period, which could be explained by assuming that beta A
      peptides are unable to accumulate in NECs due to their rapid degradation, thereby
      allowing NECs to fully recover within 48 h.

PMID- 15870897
TI  - Expression of the novel Snai-related zinc-finger transcription factor gene Smuc
      during mouse development.
AB  - The Snai-related proteins are zinc-finger transcription factors that play
      important roles in cell-fate determination. We previously cloned a novel Snai
      related gene known as snail-related transcription factor of muscle cells (Smuc)
      or, more recently, as snail homologue 3 (Snai3). In the present study, we
      investigated the functional roles of Smuc using in situ hybridization analysis at
      various stages of mouse development. Smuc was not detected until 12.5 days post
      coitus (dpc). Its expression was observed in the skeletal muscles and thymus at
      13.5 and 15.5 dpc, respectively, and these remained the major sites of Smuc
      expression until postnatal day 2. No Smuc expression was observed in the heart,
      large vessels, lungs, liver, kidney or brain. These results indicate that Smuc
      might be involved in the morphogenesis of the skeletal muscles and thymus at a
      relatively late stage of mouse development.

PMID- 15870896
TI  - Increased glucose tolerance in N-type Ca2+ channel alpha(1B)-subunit gene
      deficient mice.
AB  - The voltage-dependent N-type Ca2+ channel is localized in the plasma membrane of
      insulin-releasing beta-cells and glucagon-releasing alpha-cells in the islets of
      Langerhans in the pancreas. To examine the contribution of N-type Ca2+ channel to
      glucose homeostasis, we performed glucose tolerance and insulin tolerance tests
      with N-type Ca2+ channel alpha(1B)-subunit-deficient mice on a normal or high-fat
      diet. The fasting glucose level in homozygous mice on the normal diet was
      significantly lower than those in wild and heterozygous mice. In glucose
      tolerance tests, the homozygous mice showed a higher glucose clearance rate and a
      similar pattern of insulin levels to those of wild and heterozygous mice. In
      insulin tolerance tests, glucose clearance rates showed no significant difference
      among wild, heterozygous and homozygous mice. In animals on the high-fat diet,
      food consumption was the same among wild, heterozygous and homozygous mice, but
      body weight gain was reduced in homozygous mice. After 8 weeks of the high-fat
      diet, homozygous mice showed lower fasting glucose levels and exhibited higher
      glucose clearance and lower insulin levels than wild or heterozygous mice in
      glucose tolerance tests. Glucose clearance rates showed no significant difference
      among wild, heterozygous and homozygous mice in insulin tolerance tests. After 10
      weeks of the high-fat diet, the alpha(1B)-deficient homozygous mice showed lower
      lipid deposition in liver and lower plasma glucagon, leptin and triglyceride
      levels than wild or heterozygous mice. These results suggest that N-type Ca2+
      channels play a role in insulin and glucagon release, and that N-type Ca2+
      channel alpha(1B)-subunit deficient mice show improved glucose tolerance without
      any change in insulin sensitivity. Thus, N-type Ca2+ channel blockers might be
      candidate anti-diabetic/anti-obesity agents.

PMID- 15870898
TI  - Cloning and characterization of a novel intronless lactate dehydrogenase gene in
      human testis.
AB  - Using cDNA microarray hybridization from a human testicular cDNA library, one
      gene named lactate dehydrogenase A-like gene (LDHL, also known as LDHL6B) was
      cloned. LDHL exhibited 3.8-fold difference at expression level between adult and
      fetal human testes. The full cDNA length of LDHL is 1680 bp and had a 1145 bp
      open reading frame, which encoded a 41.9 kDa protein of 381 amino acids. Sequence
      analysis showed that LDHL harbors all the domains (one lactate/malate
      dehydrogenase, NAD binding domain and one lactate/malate dehydrogenase,
      alpha/beta C-terminal domain) in lactate dehydrogenase gene family. Blasting
      human genome database localized LDHL to human chromosome 15q22.2 and it was an
      intronless gene. Results of multiple-tissue PCR and real-time PCR showed that
      LDHL expressed mainly in testis and its mRNA abundance was testis development
      related. In summary, LDHL is believed to be involved in testis development and
      spermatogenesis.

PMID- 15870899
TI  - Immunohistochemical detection of hMLH1 and hMSH2 proteins in vulvar carcinoma.
AB  - The immunohistochemical (IHC) detection of MMR proteins is an accurate and rapid
      method to predict the presence of defective DNA MMR genes. MMR protein expression
      could also serve as a prognostic indicator of human cancers. The results of many
      studies demonstrate the usefulness of IHC tests with monoclonal antibodies MSH2
      and MLH1 in screening the microsatellite sequence instability within both
      spontaneous and hereditary malignant neoplasms. The aim of our study was to
      perform an IHC estimation of the hMLH1 and hMSH2 expression in a subset of vulvar
      carcinomas according to HPV 16/18 status. The level of MMR proteins was further
      analyzed in relation to histoclinical features of the disease in either HPV
      positive or -negative cancers. We identified archival diagnostic phase tissue
      specimens from 46 cases of vulvar cancer. From the same paraffin blocks
      containing material from the margin of surgical section during vulvectomy, normal
      epithelial tissue fragments were collected and designated as the control group.
      The characteristic of the lesion was examined in comparison with the presence of
      HPV DNA. Identification of the HPV 16/18 types was performed using PCR. IgG1
      monoclonal antibodies detecting those epitopes characteristic for hMLH1 and hMSH2
      were used in the study. In the analyzed cases of vulvar cancer, we have observed
      increased expression of proteins of both hMSH2 and hMLH1 genes compared to the
      control group. A comparison of the hMLH1 and hMSH2 protein expression levels
      showed that hMSH2 expression was higher than that of hMLH1 in the case of vulvar
      carcinomas. The performed analysis of correlation between individual parameters
      did not reveal statistically significant relationship with both the gradient and
      status of HPV 16/18. hMSH2 and hMLH1 were definitely interrelated.

PMID- 15870900
TI  - Interleukin-15 decreases lipid intestinal absorption.
AB  - Administration of a single acute intravenous injection of interleukin-15 (IL-15)
      (100 microg/kg bw) to rats resulted in a significant decrease (22%) in
      triacylglycerol absorption, as measured by using [14C]-triolein load. The
      cytokine, however, did not influence the oxidation of the exogenously
      administered lipid or the tissue uptake of [14C]-triolein; this is in concordance
      with the lack of effects found in the measurement of the tissue lipoprotein
      lipase activity. Concerning the mechanism involved in the decreased intestinal
      absorption associated with IL-15 administration, the results presented clearly
      demonstrate that changes in gastric emptying and intestinal mobility are not
      involved, as the effect is specific for triacylglycerols. In conclusion,
      intestinal absorption may be an additional mechanism to take into consideration
      to explain the 'anti-fat' effect of this cytokine.

PMID- 15870901
TI  - Evidence that orexins A and B stimulate insulin secretion from rat pancreatic
      islets via both receptor subtypes.
AB  - Orexins are recently identified neuropeptides that appear to play a role in the
      regulation of energy homeostasis and arousal. They bind to and activate two
      closely related G protein-coupled receptors (OXR1 and OXR2), previously described
      as orphans. In this study we examined involvement of orexins in regulation of
      insulin secretion from rat pancreatic islets utilizing an in situ perfused
      pancreas and isolated pancreatic islet models. By means of RT-PCR we found that
      both OXR1 and OXR2 are expressed in rat pancreatic islets. Furthermore, the
      expression levels of OXR1 were higher than OXR2. In both experimental models
      applied, orexins A and B (1, 10 and 100 nmol/l) concentration dependently
      stimulated insulin secretion at two different glucose concentrations (6.66 or
      26.4 mmol/l), with orexin A being more potent than orexin B. This study
      demonstrates that orexins A and B modulate insulin secretion in vitro.

PMID- 15870902
TI  - Beta-catenin cleavage in non-apoptotic cells with reduced cell adhesion activity.
AB  - Beta-catenin functions both as a regulator of cadherin-mediated cell-cell
      adhesion and a mediator of Wnt signaling. Recently, caspase-3-dependent cleavage
      of beta-catenin was demonstrated to occur during apoptosis. Here, we show that
      beta-catenin is proteolytically cleaved in G401 Wilms' tumor cells that were
      detached from the culture dish. Beta-catenin cleavage products of the same
      electrophoretic mobility were detected in G401 cells after induction of apoptosis
      with staurosporine and cell cycle arrest by aphidicolin. The detached cells show
      no sign of anoikis and approximately 90% of the floating cells were able to
      reattach to new dishes. Furthermore, beta-catenin was not cleaved in cells
      cultured on dishes coated with poly(2-hydroxyethylmethacrylate), which inhibits
      cellular attachment on the dishes, with approximately 90% of cells viable under
      these conditions. All beta-catenin cleavage products lost N-terminal and C
      terminal regions and were unable to associate with alpha-catenin, which is
      responsible for actin filament binding and organization. However, they were still
      able to associate with E-cadherin. Aggregation assays revealed that the floating
      cells had weak aggregation compared with the attached cells. These results
      suggest that the cleavage of beta-catenin during cell detachment functions at
      least in part to remove the alpha-catenin-binding domain, thereby reducing cell
      adhesion activity.

PMID- 15870903
TI  - Inhibition of interleukin-8 production in the human colonic epithelial cell line
      HT-29 by 18 beta-glycyrrhetinic acid.
AB  - Interleukin (IL)-8 plays a central role in the initiation and maintenance of
      inflammatory responses in the inflammatory bowel disease. The proinflammatory
      cytokine-mediated production of IL-8 requires activation of various kinases,
      which leads to the I kappa B degradation and NF-kappa B activation. We
      investigated the role of 18 beta-glycyrrhetinic acid (GA), a saponin isolated
      from licorice roots, on TNF-alpha-induced IL-8 production in human colonic
      epithelial cells. HT29 cells were stimulated with TNF-alpha in the presence or
      absence of GA (1, 5 or 10 microM). IL-8 production was measured by enzyme-linked
      immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction
      analysis, and the mitogen-activated protein kinases (MAPKs) activation and I
      kappa B alpha degradation were determined by Western blot analysis. GA suppressed
      TNF-alpha-induced IL-8 production in a concentration-dependent manner. In
      addition, GA inhibited TNF-alpha-induced phosphorylation of p38 MAPK and
      extracellular-regulated kinases (ERK), I kappa B alpha degradation, and NF-kappa
      B activation. These results suggest that GA has the inhibitory effects on TNF
      alpha-induced IL-8 production in the intestinal epithelial cells through blockade
      in the phosphorylation of MAPKs, following I kappa B alpha degradation and NF
      kappa B activation.

PMID- 15870904
TI  - Increased myocardial N-myristoyltransferase activity in rotenone model of
      Parkinsonism.
AB  - There is widespread brain pathology in Parkinson's disease (PD), with the primary
      pathology in the substantia nigra. Oxidative stress is believed to play a role in
      cell death in PD. Rotenone is a mitochondrial toxin which can produce Parkinson
      syndrome (PS) in rats. Myristoyl-CoA:protein N-myristoyltransferase (NMT), which
      catalyzes the co-translational transfer of myristate from myristoyl-CoA to the
      amino-terminal glycine residue of selected polypeptides, is increased in the
      myocardium of ischemia-reperfusion rat model myocardium. Animals received
      rotoneone (n=10) or placebo vehicle (n=6) via Alzet osmotic pumps. Mean cardiac
      muscle NMT activity of placebo treated (control) rats was 0.608+/-0.366 units/mg
      protein. Rats with mild or no detectable PS features on rotenone showed slight
      (mean 0.853+/-0.192) but insignificantly increased activity. Rats that had
      moderately severe PS features had higher level of NMT activity (mean 1.223+/
      0.057), which was borderline significant compared to controls (P=0.066). Rats
      with severe PS features had the highest NMT activity (1.353+/-0.128) which was
      significantly greater compared to controls (P=0.003) and to the rats that had
      equivocal or no motor slowing (P=0.005). Our data show cardiac metabolic
      dysfunction in a rotenone rat model of PS. The severity of this change correlates
      with the severity of motor manifestations. Further studies of NMT activity in
      human PD cases and patients with cardiomyopathy of unknown cause may provide
      valuable information in these disorders.

PMID- 15870905
TI  - Arginin-vasopressin regulates proliferative activity of the regenerating rat
      adrenal cortex.
AB  - Enucleation-induced adrenal regeneration is a classic model to investigate
      adrenocortical proliferation in vivo, which is dependent not only on pituitary
      ACTH release, but also on various other neural and endocrine signals. Arginin
      vasopressin (AVP), mainly acting via V1 receptors, regulates hypothalamic
      hypophyseal-adrenal axis function, acting on both its central and peripheral
      branches. Here, we studied whether endogenous AVP system modulates rat adrenal
      regeneration. Reverse transcription-polymerase chain reaction (PCR) detected only
      the mRNAs of V1a and V1b receptors in normal and regenerating adrenals. The
      expression was very low, and semi-quantitative conventional and real-time PCR
      showed that it was down-regulated in regenerating adrenals in relation to the
      time elapsed from enucleation. AVP (three subcutaneous injections 28, 16 and 4 h
      before sacrifice) raised metaphase index at day 5, but not at day 8 of
      regeneration. Unexpectedly, both V1-receptor and V2-receptor antagonists
      increased metaphase index at days 5 and 8 of regeneration. Neither AVP nor AVP
      receptor antagonists affected plasma levels of corticosterone in rats bearing
      regenerating adrenals. It is concluded that AVP, acting via V1 receptors located
      in adrenals, exerts a stimulating effects on adrenal regeneration. Due to the
      down-regulation of V1-receptor expression in regenerating adrenals, this effect
      is very weak and is easily overcome by a tonic inhibitory action of endogenous
      AVP systems probably involving extra-adrenal indirect mechanisms.

PMID- 15870906
TI  - Properties of Sindbis virus vectors produced with a chimeric split helper system.
AB  - We have evaluated a chimeric, two-component Sindbis virus packaging system. As
      expected, use of this combination of two modified helper RNA species prevented
      formation of infection competent Sindbis viruses as analyzed by serial passaging.
      We observed, however, that vectors produced using this method were able to spread
      in BHK cell cultures and formed clusters of transgene positive cells that did not
      display cytopathic effects for up to 3 days post-transduction. Formation of
      spreading Sindbis virus vectors required only one of the helper components--the
      chimera with a deleted Ross River virus capsid and the Sindbis virus envelope
      glycoproteins. Spreading was also demonstrated in two rat glioma cell lines, 9L
      and BT4C, showing that this phenomenon was not limited to BHK cells. Our results
      warrant further characterization of split helper Sindbis virus vectors and imply
      their utility in gene therapy approaches where spreading of transgene expression
      and consequently high gene transfer rate could be beneficial.

PMID- 15870907
TI  - Resveratrol affects X-ray induced apoptosis and cell cycle delay in human cells
      in vitro.
AB  - Many studies in human and mammalian cells have shown the involvement of
      resveratrol in the modulation of several biological processes, including the
      regulation of carcinogenesis. However, the molecular mechanisms underlying its
      antitumorigenic activity are still not defined. There is great interest in
      developing new agents that can modify the efficacy of radiation therapy. The aim
      of the present study was to investigate the cellular response to treatments with
      X rays and resveratrol, alone or in combination, in terms of DNA damage, cell
      cycle delays and induction of apoptosis. Lymphoblastoid cells AHH-1 were treated
      and analysed at successive sampling times in order to study the induction of DNA
      breaks using the Comet assay and the induction of apoptosis and cell cycle
      modulation through cytofluorimetric analysis. Our results suggest that
      resveratrol causes the induction of apoptosis and a block of cell cycle
      progression at an early step of S-phase. Furthermore, resveratrol mitigates the
      apoptotic clearance of irradiated cells and prevents the G2 phase cell cycle
      arrest induced by X-rays.

PMID- 15870908
TI  - Effects of plant phenolics and grape extracts from Greek varieties of Vitis
      vinifera on Mitomycin C and topoisomerase I-induced nicking of DNA.
AB  - In recent years, a number of reports have shown the anticancer activity of grape
      extracts and wine against various types of cancer such as breast, lung and
      gastric cancer. This property is mainly attributed to the plant polyphenols
      identified in grapes. The aim of the present study was to investigate the
      mechanisms by which grape extracts and plant polyphenols found in them exert
      their chemopreventive and antitumour activities. Thus, aqueous and methanolic
      extracts from two Greek varieties of Vitis vinifera, fractions enriched in
      polyphenols of these extracts and polyphenolics (caffeic acid, ferulic acid,
      gallic acid, protocatechuic acid and rutin) found in grapes were screened using
      two in vitro assays: i) the topoisomerase I relaxation assay and ii) the
      mitomycin C-induced DNA strand breakage. The grape extracts, the polyphenol-rich
      fractions and some of the polyphenolics (caffeic acid and protocatechuic acid)
      were potent inhibitors of topoisomerase I, indicating that the inhibition of this
      enzyme may be one of the mechanisms accounting for the anticancer activity of
      these compounds. Moreover, the grape extracts inhibited the mitomycin C-induced
      DNA strand breakage suggesting that they could prevent ROS-mediated DNA damage.
      On the other hand, the polyphenol-rich fractions and the plant polyphenols
      enhanced the mitomycin C-induced DNA strand breakage indicating prooxidant
      activity. Thus, it is of interest that whole grape extracts act as
      chemopreventive agents by inhibiting topo I and mitomycin C-induced DNA damage,
      while polyphenol enriched fractions and plant polyphenolics exert prooxidant
      activity leading to enhancement of DNA damage which may account for the cytotoxic
      and apoptosis-inducing properties of plant polyphenols against cancer cells.

PMID- 15870909
TI  - Receptor-mediated down-regulation of neutral endopeptidase (NEP; EC 3.4.24.11;
      CD10) on immature B lymphocytes by dexamethasone.
AB  - Neutral endopeptidase is a membrane bound enzyme with various functions depending
      on cell type or tissue origin. Normal development and differentiation of immature
      B lymphocytes depends on expression of CD10/NEP on B cell progenitors and bone
      marrow stromal cells. Synthetic glucocorticoid dexamethasone (dex), an
      immunosuppressive and anti-inflammatory drug, was shown to be a potent modulator
      of CD10/NEP expressed on cells of non-hematopoietic origin. We investigated the
      effect of dex on expression of differentiation marker CD10/NEP on immature B
      cells. The drug was applied in concentrations corresponding to the physiological
      range. CD10/NEP was measured at three levels of expression: mRNA (by means of
      duplex PCR), membrane protein marker (FACS analysis) and enzyme activity
      (hydrolysis of a selective chromogenic substrate). Dex down-regulated CD10/NEP
      expression on immature B cell line NALM-6 in a concentration- and time-dependent
      fashion. The effect was detected at all three levels. Dex-induced CD10/NEP down
      regulation was mediated via glucocorticoid receptors (GR), as it was fully
      abrogated by a GR antagonist, RU 38486. That occurred at all three levels. The
      mechanism of dex-induced CD10/NEP down-regulation is not likely to include
      selection of cells that are CD10low since the effect was partly reversible after
      the removal of dex. However, dex-induced CD10/NEP down-regulation did include
      decreased transcription of the CD10 mRNA. Transcriptional inhibitor actinomycin D
      completely abolished dex-induced CD10/NEP down-regulation. Since differentiation
      of normal B lymphocytes is associated with down-regulation of CD10/NEP, the data
      presented suggest that low, physiologically relevant concentrations of
      glucocorticoids (such as observed in acute stress) may play a regulatory role in
      normal development and maturation of B lymphocytes.

PMID- 15870910
TI  - Melanin-concentrating hormone enhances sucrose intake.
AB  - Melanin-concentrating hormone (MCH) is known to be an important regulator for
      feeding and energy balance. MCH was recently reported to stimulate water intake
      independent of food intake. The purpose of the present study is to examine the
      dipsogenic response of MCH with special emphasis on sweetened beverages, the
      preference for which is well documented in diabetic animals. Our results showed
      that intracerebroventricular injection of MCH acutely increased food as well as
      water intake. Human (h)MCH and salmon (s)MCH increased water intake independent
      of food intake, which was not suppressed by angiotensin antagonists. hMCH and
      sMCH significantly increased both sucrose solution and food intake; on the other
      hand, agouti-related protein (AgRP) stimulated food but not sucrose intake when
      provided simultaneously. MCH-treated rats significantly increased the ingestion
      of sucrose and glucose solution, but not of saccharin, indicating that MCH
      induced dipsogenic response is more related to caloric content than sweet taste
      per se. Significant correlation was observed between the sucrose intake and the
      mRNA expression of MCH and MCHR1 in normal rats. These results indicate that MCH
      may be an important regulator of sugar intake in normal as well as in obese
      diabetic animals.

PMID- 15870911
TI  - Intracerebroventricularly administered urocortin inhibits gastric emptying in
      mice.
AB  - Urocortin, a recently identified member of the corticotropin-releasing factor
      (CRF) family, is implicated in the central control of appetite and energy
      metabolism. We previously reported that peripherally administered urocortin
      inhibits gastric emptying in conscious mice. In this study, we investigated the
      effect of intracerebroventricularly administered urocortin on gastric emptying,
      food intake and body weight in mice. Urocortin decreased food intake and body
      weight gain more potently than CRF. It significantly decreased gastric emptying
      of a solid meal; an effect that was inhibited by simultaneous administration of
      alpha-helical CRF9-41, a CRF antagonist. These results suggest that the potent
      anorectic properties of urocortin may be partly due to the anti-gastroprokinetic
      activity of the peptide.

PMID- 15870912
TI  - Identification and characterization of rat Dact1 and Dact2 genes in silico.
AB  - DACT1 (DAPPER1), Frizzled receptors, MUSK receptor, VANGL1, VANGL2, PRICKLE1,
      PRICKLE2, DAAM1, Casein kinases, MARK3 (PAR1), PP2C, AXIN1, AXIN2, NKD1, NKD2,
      FRAT1, FRAT2 and CXXC4 are WNT signaling molecules associating with Dishevelled
      family proteins. Human DACT1 is the ortholog of Xenopus Dapper and Frodo, and
      human DACT2 (DAPPER2) is the paralog of human DACT1. Here, we identified and
      characterized rat Dact1 (Dapper1) and Dact2 (Dapper2) genes by using
      bioinformatics. Rat Dact1 gene, consisting of four exons, was located within
      AC136677.3 genome sequence. Rat Dact2 gene, consisting of four exons, was located
      within AC139434.3 genome sequence. Dact1 was mapped to rat chromosome 6q24, and
      Dact2 gene to rat chromosome 1q12. Rat Dact1 (778 aa) showed 93.7, 82.9, 60.3,
      58.7 and 48.6% total-amino-acid identity with mouse Dact1, human DACT1, Xenopus
      Dapper, Xenopus Frodo and zebrafish dact1, respectively. Rat Dact2 (768 aa)
      showed 86.6, 59.6 and 38.3% total-amino-acid identity with mouse Dact2, human
      DACT2 and zebrafish dact2, respectively. Dact1 orthologs were more evolutionarily
      conserved than Dact2 orthologs. Seven DAPH domains (DAPH1-DAPH7), originally
      identified as the regions conserved between human DACT1 and DACT2, were conserved
      among mammalian Dact1 orthologs and Dact2 orthologs. DAPH2 domain, corresponding
      to the Leucine zipper motif, was located within the coiled-coil region. DAPH3
      domain was the Serine rich region. DAPH7 domain was the C-terminal PDZ binding
      region. This is the first report on the rat Dact1 and Dact2 genes.

PMID- 15870913
TI  - Comparative genomics on Fzd7 orthologs.
AB  - WNT signaling pathway networks with Hedgehog and Notch signaling pathways during
      carcinogenesis and embryogenesis. FZD7 is up-regulated in gastric cancer,
      esophageal cancer, and hepatocellular carcinoma (HCC). Here we identified and
      characterized rat Fzd7 gene by using bioinformatics. Rat Fzd7 gene was identified
      within AC136379.2 genome sequence. The 5'-flanking region and exonic region were
      well conserved among mammalian Fzd7 orthologs. Nucleotide position 153000-152216
      of AC136379.2 genome sequence was identified as the evolutionarily conserved
      promoter region of rat Fzd7 gene, and nucleotide position 2273-3046 of AC069148.6
      genome sequence as the evolutionarily conserved promoter region of human FZD7
      gene. Match program revealed that PAX4-binding site was conserved among rat Fzd7,
      mouse Fzd7 and human FZD7 promoters. Rat Fzd7 (572 aa) was a seven-transmembrane
      type Wnt receptor, which showed 99.3, 96.9, 87.4, 85.5, 79.5 and 79.0% total
      amino-acid identity with mouse Fzd7, human FZD7, chicken fzd7, Xenopus fzd7,
      zebrafish fzd7a and fzd7b, respectively. Frizzled (Fz) domain within the N
      terminal extracellular region, Leucine zipper motif around the fifth
      transmembrane (TM5) region, Dishevelled (Dvl)- and Magi3-binding motifs within
      the C-terminal cytoplasmic region were conserved among vertebrate Fzd7 orthologs.
      Leucine zipper motif around the TM5 region of Fzd7 orthologs was disrupted in
      FzE3 aberrant cDNA due to multiple cloning artifacts or sequencing errors. These
      facts indicate that experimental data obtained by using FzE3 cDNA do not always
      reflect the functions of Fzd7 orthologs.

PMID- 15870914
TI  - Nanotechnology blooms, at last (Review).
AB  - Clinical trials for deadly pancreatic cancer have recently opened on two
      continents to evaluate the safety and efficacy of engineered nanoparticles guided
      by a targeted delivery system (TDS) to overcome the daunting barriers of
      turbulence, dilution, filtration, and inactivation encountered in the human
      circulatory system to deliver a killing designer gene to metastatic tumors that
      are refractory to conventional chemotherapy. The first patients receiving
      multiple intravenous infusions of the TDS-encapsulated genetic bullets have all
      responded favorably, prompting the FDA to grant orphan drug status for the
      nanobiotic medicine, Rexin-G, to assist in the development of this new cancer
      treatment. This review/commentary is an effort to translate the arcane
      terminology of physiology, biochemistry, and molecular genetics into the more
      generally accessible language of nanotechnology and medical delivery. While the
      text is somewhat erudite and laden at times with inconspicuous literary
      allusions, descriptions of the elegant bioengineering of nano-scale gene delivery
      vehicles are clear and the numerous references to classical mechanics of the
      Industrial Age are helpful.

PMID- 15870915
TI  - Allelic loss of the DNA repair gene OGG1 against oxidative damage in esophageal
      squamous cell carcinoma.
AB  - Esophageal tissue often undergoes oxidative damage from exposure to cigarettes
      and alcohol. The OGG1 gene plays a major role in maintaining genetic integrity by
      removing 8-oxoguanine (8-oxoG) in cellular DNA by way of the base excision repair
      pathway. The OGG1 gene is located at 3p26.2 of the human chromosome. Although
      deletion in the 3p region is frequently found in cases of esophageal cancer, few
      reports have focused on the allelic loss of the OGG1 gene. Using 24 samples of
      surgically-resected esophageal cancer tissue, we assessed the allelic loss of the
      OGG1 gene with a set of three microsatellite markers that flank the OGG1 gene. We
      compared the loss of homozygosity status for the OGG1 gene with clinicopathologic
      factors, as well as OGG1 expression and accumulation of 8-oxoG, which was
      estimated in an immunohistochemical study. Of 24 cases, 20 were suitable for
      determining OGG1 allelic loss. Allelic loss of OGG1 was observed in 6 of 20 (30%)
      cases. An inverse correlation between OGG1 allelic loss and OGG1 expression was
      weakly observed (p=0.051). In contrast, OGG1 allelic loss showed a positive
      correlation with 8-oxoG accumulation, although the correlation was not
      statistically significant (0.095). OGG1 allelic loss was observed in 30% of
      patients in our study, a lower frequency than that reported in other
      malignancies, and correlated with reduced OGG1 expression and 8-oxoG
      accumulation. These findings suggest that attenuated OGG1 expression contributes
      to 8-oxoG accumulation under oxidative stress, resulting in cancer development in
      the esophagus. Thus, OGG1 allelic loss is related to carcinogenesis by oxidative
      stress rather than cancer progression in esophageal cancer.

PMID- 15870916
TI  - Effect of retinol on radiation- and estrogen-induced neoplastic transformation of
      human breast epithelial cells.
AB  - Clinical, epidemiological and experimental findings have provided evidence
      supporting a role of free radicals in the etiology of cancer. Free radical
      production is enhanced in many disease states, by carcinogen exposure, and under
      conditions of stress contributing widely to cancer development in humans. We have
      established an experimental breast cancer model to examine the effects of all
      trans-retinol (retinol/vitamin A) on the production of free radicals in human
      breast epithelial cells induced by high linear energy transfer (LET)-radiation in
      the presence of 17beta estradiol. The following cell lines were used in these
      studies: the MCF-10F cell line, a spontaneously immortalized human breast
      epithelial cell line. Alpha 5 derived from MCF-10F cells irradiated with two
      separated doses of 60 cGy alpha particles in the presence of estrogens (60E/60E).
      Tumor 2, from a tumor formed in nude mice after injection with the cell line
      alpha 5. Tumor 3, from secondary tumor formed from injecting tumor 2 cells into
      nude mice. Each of the cell types examined had significantly elevated H(2)O(2)
      production levels compared to MCF-10F control cells (p<0.001). Retinol (1
      microl/ml) significantly (p<0.05) decreased H(2)O(2) production in all cell types
      examined. Retinol significantly decreased (p<0.05) invasive capabilities of cells
      across matrigel coated invasion chambers and significantly reduced (p<0.05) PCNA,
      Fra-1, mutant p53 and increased Rb protein expression levels in comparison to non
      retinol-treated ones when assayed using immunofluorescent staining coupled with
      confocal microscopy. The reduced H(2)O(2) production, decrease in cell invasive
      capabilities and alterations in protein expression levels suggest that retinol
      can be used as a chemopreventive agent in human breast cancer.

PMID- 15870917
TI  - Establishment and characterization of a human non-small cell lung cancer cell
      line.
AB  - Lung cancer is one of the most common causes of cancer death worldwide. Although
      many efforts have been made to explore the mechanisms involved in the development
      of lung cancer, the genetic events involved in the pathogenesis of lung cancer
      are still unclear. For a better mechanistic scope of study, a well-established
      cellular model is essential. We report the establishment of a squamous cell
      carcinoma (SCC) cell line of human lung, SCC-37. Chromosomal abnormalities and
      global genomic alterations of SCC-37 were studied by spectral karyotyping (SKY)
      and comparative genomic hybridization (CGH), respectively. Results showed that
      SCC-37 was a hypodiploid with complex chromosomal rearrangements. Some of the
      alterations, such as the gain of 1q25-qter in SCC-37, have been correlated to the
      tumor recurrence of non-small cell lung cancer (NSCLC). Other interesting
      findings include the amplification of 3q25-qter and 12q13, suggesting the
      existence of important oncogenes in the amplicons. This cell line may thus
      provide a useful cellular resource for studying the pathogenesis of SCC of the
      lung in the future.

PMID- 15870918
TI  - Renal cell carcinoma- and pheochromocytoma-specific altered gene expression
      profiles in VHL mutant clones.
AB  - Von Hippel-Lindau (VHL) disease is associated with various missense germline
      mutations in the VHL tumor suppressor gene. Some are associated with type 1 VHL
      disease, renal cell carcinoma (RCC) without pheochromocytoma, while others are
      associated with type 2A or 2B VHL disease, pheochromocytoma without and with RCC,
      respectively. These mutations may cause substitutions of specific amino acid
      residue and functional change of VHL protein (pVHL), which leads to the
      oncogenesis of the particular tumor types that characterize the different VHL
      disease types. To investigate, we transfected a pVHL-null RCC cell line with
      plasmids expressing wild-type pVHL (WT) or pVHL bearing 1 of 3 point mutations.
      These occur in the pVHL regions that bind hypoxia-inducible factor alpha (HIF
      alpha ) or Elongin C. Microarray analysis showed that the clones bearing a
      mutation in the elongin-binding region (mutant 167) were unique, as many more
      genes were suppressed than up-regulated. The other two mutant groups, which bear
      a mutation in the HIF-alpha -binding region (mutants 98 and 111), showed the
      opposite pattern. The 167 mutation is associated with type 2B VHL disease. Real
      time PCR analysis confirmed the altered expression of selected genes in the
      clones. Relative to WT, stratifin (14-3-3 sigma) and lysyl oxidase-like 1 were
      down-regulated in the 167 mutants, while the transforming growth factor beta
      induced protein (beta ig-h3) was up-regulated in the 111 mutants. Thus, the
      location of pVHL mutations results in distinct gene expression patterns.
      Moreover, a mutation in the elongin-binding domain may induce type 2B tumors
      through different molecular pathways compared to those induced by type 1- or 2A
      associated mutations in the HIF-alpha -binding region.

PMID- 15870919
TI  - Expression of matrix metalloproteinases (MMPs) in cultured hepatocellular
      carcinoma (HCC) cells and surgically resected HCC tissues.
AB  - Matrix metalloproteinases (MMPs) relate to the growth and infiltration of cancer
      cells, but the frequency and amount of their expression are not yet fully
      examined in hepatocellular carcinoma. Expression of MMPs (MMP-2, MMP-7, MMP-9,
      MT1-MMP, MT2-MMP, MT3-MMP) and tissue inhibitors of metalloproteinase (TIMP: TIMP
      1, TIMP-2) was investigated on cultured hepatocellular carcinoma (HCC) cells and
      surgically resected HCC tissues. The cultured cells and tissues expressed MMPs
      and TIMPs at various degrees, and high expression was observed for MMP-2, MMP-9,
      MT1-MMP and TIMP-2. Expression of MMP-7, MT2-MMP and TIMP-1 was found at a low
      frequency and a low amount in both the cells and the tissues. MMP-2 was expressed
      in various cells: HCC cells, vascular wall and sinusoidal endothelial cells in
      the cancer area of surgically resected tissues; and hepatocytes, bile duct cells,
      vascular wall, macrophages and Kupffer cells in the non-cancerous area. MMPs and
      TIMPs were expressed at a relatively high frequency in hepatocytes of the
      cancerous area and surrounding non-cancerous area as well as in the other cells
      and tissues. MMPs and TIMPs may be involved in the progression of hepatocellular
      carcinoma including the infiltration of cancer cells.

PMID- 15870920
TI  - Characterization of the prostaglandin biosynthetic pathway in non-small cell lung
      cancer: a comparison with small cell lung cancer and correlation with
      angiogenesis, angiogenic factors and metastases.
AB  - To investigate the components of the prostaglandin biosynthetic pathway, the
      characteristics of cyclooxygenase (COX)-1, COX-2, hematopoietic prostaglandin D
      synthase (hPGDS), microsomal prostaglandin E synthase (mPGES), and thromboxane
      synthase (TXS) were examined for autopsied cases with small cell lung cancer
      (SCLC) and non-small cell lung cancer (NSCLC). Autopsied patients (n=120) with
      lung cancer were examined, of whom 25 had SCLC and 95 had NSCLC. Immunostaining
      was performed for COX-1, COX-2, hPGDS, mPGES, TXS, CD34, vascular endothelial
      growth factor (VEGF), and basic fibroblastic growth factor (bFGF). The
      immunostaining scores of the prostaglandin biosynthetic pathway markers were
      significantly higher for adenocarcinoma than for SCLC (p<0.0001). In addition,
      there were significant correlations between two markers of the prostaglandin
      biosynthetic pathway for cases with SCLC and NSCLC. For NSCLC, the mean
      immunostaining scores for the prostaglandin biosynthetic pathway markers were
      significantly higher for cases with high count groups than low count groups for
      MVD, VEGF and bFGF, except COX-2 and MVD, and COX-2 and bFGF. The mean
      immunostaining scores for COX-1, COX-2, mPGES, and TXS were significantly higher
      for cases with more metastatic organs who had NSCLC. Prostaglandin biosynthetic
      pathway markers may act synergistically and enhance tumor angiogenesis, the
      expression of angiogenic factors, and metastases in patients with NSCLC.

PMID- 15870921
TI  - Evaluation of endoscopic mucosal resection and nodal micrometastasis in pN0
      submucosal gastric cancer.
AB  - Endoscopic mucosal resection (EMR) is a minimally invasive, standard treatment
      for intramucosal (early) gastric cancers, but is not standard for submucosal
      gastric cancers based on existing criteria. We evaluated the possibility of
      extending EMR as a therapy for submucosal gastric cancers by analyzing nodal
      micrometastasis through immunohistochemical staining in patients with apparent
      node-negative submucosal gastric cancer, the patients for whom EMR might be
      appropriate. We used anti-cytokeratin (AE1/AE3) antibody to immunohistochemically
      detect nodal micrometastasis that was not identified by routine pathological
      examination in 162 patients (total, 2048 lymph nodes) with apparent node-negative
      submucosal gastric cancer. The relationship between the incidence of nodal
      micrometastasis and clinicopathological factors was analyzed. Micrometastasis was
      detected in 45 of 2048 nodes (2.2%), representing 31 of 162 patients (19%). A
      significantly high incidence of nodal micrometastasis was found with submucosal
      cancers of large size (>2 cm), as well as with tumors that showed lymphatic or
      venous invasion and deeper submucosal invasion (p<0.0001). Nodal micrometastasis
      was also recognized in 2 cases of histologically well-differentiated tumors with
      focal submucosal invasion without venous or lymphatic invasion. Of the 162
      patients, only 2 died of recurrent disease regardless of nodal involvement. Based
      on the present results, risk factors for nodal micrometastasis are tumor size,
      presence of lymphatic-vascular invasion, and depth of tumor, which are nearly the
      same as those established in previous pathological studies that used hematoxylin
      and eosin staining. We conclude that EMR is not recommended for patients with
      submucosal gastric cancer.

PMID- 15870922
TI  - Diffuse large B-cell primary gastric lymphoma treated successfully with the CD20
      monoclonal antibody (rituximab): a case with severe liver dysfunction due to
      liver cirrhosis and hepatocellular carcinoma.
AB  - Primary gastric lymphoma is relatively rare in the scope of gastric malignancies.
      Here we report a case of diffuse large B-cell primary gastric lymphoma treated
      successfully with the CD20 monoclonal antibody, rituximab, alone. Because the
      patient had a complication of severe liver dysfunction due to hepatitis C virus
      induced-liver cirrhosis and hepatocellular carcinoma, it was difficult to treat
      the primary gastric lymphoma using standard therapy such as surgical resection
      and cocktail chemotherapy. Therefore, rituximab was administered to the patient,
      resulting in complete remission of the primary gastric lymphoma. This case
      indicates that monotherapy using only rituximab may be a promising option for the
      treatment of patients with diffuse large B-cell lymphoma accompanied by severe
      liver dysfunction.

PMID- 15870924
TI  - Hepatoma-derived growth factor as a prognostic marker in completely resected non
      small-cell lung cancer.
AB  - Hepatoma-derived growth factor (HDGF), unrelated to hepatocyte growth factor, is
      a heparin-binding protein originally purified from human hepatoma HuH-7 cells.
      HDGF exhibits mitogenic activities for certain hepatoma cells, fibroblasts and
      vascular smooth muscle cells, and angiogenic activities through nuclear
      targeting. Recently, HDGF was found to be a mitogen for lung epithelial cells in
      vitro and in vivo. This suggests that HDGF may play a critical role in the
      development and progression of lung cancer. We investigated,
      immunohistochemically, the relationship between HDGF expression and
      clinicopathological variables, and the prognostic significance of HDGF in 102
      patients with completely resected non-small-cell lung cancer (NSCLC: 70
      adenocarcinomas and 32 squamous cell carcinomas). To address the mechanism of
      action of HDGF, we evaluated the contribution of HDGF to tumor cell proliferation
      and intratumor angiogenesis using anti-Ki-67 and anti-CD31 antibodies,
      respectively. HDGF expression was strongly detected in the nucleus of cancer
      cells; the HDGF-labeling index (LI) was 20-95% (median 64.5%). There was no
      significant association between HDGF-expression level and clinicopathological
      variables. Patients with NSCLC showing a high HDGF-LI (> or =65%) had
      significantly worse overall and disease-free survivals than those with NSCLC
      showing a low HDGF-LI. Multivariate analysis revealed that HDGF is a significant
      independent prognostic factor, more powerful than pathological stage. Moreover,
      HDGF expression correlated with Ki-67-LI and intratumor microvessel density. We
      consider HDGF as a useful prognostic marker for patients with completely resected
      NSCLC and it may play a critical role in the pathobiology of lung cancer through
      its mitogenic and angiogenic activities.

PMID- 15870923
TI  - Up-regulation of growth factor receptor-bound protein 10 in cervical squamous
      cell carcinoma.
AB  - The Grb10 gene on chromosome 7p11.2-p12 belongs to a family of adapter proteins
      known to interact with a number of receptor tyrosine kinases, such as EGF,
      ErbB2/Her2, platelet-derived growth factor (PDGF), IGF-I receptors and vascular
      endothelial growth factor (VEGF) receptor, KDR (kinase insert domain containing
      receptor). In addition to receptor tyrosine kinases, Grb10 has also been found to
      interact with non-receptor tyrosine kinases such as Tec and Bcr-Abl, other
      cellular signaling molecules such as Raf-1, and the mitogen-activated protein
      (MAP) kinase, MEK. We demonstrated increased expression of Grb10 mRNA in more
      than one half of primary cervical squamous cell cancers (12 of 15 cases) when
      compared to corresponding non-cancerous uterine squamous cell tissues. In
      addition, immunohistochemical staining demonstrated that the Grb10 protein was
      prominent in the cytoplasm of cancer cells, whereas it was unreactive in the
      surrounding normal cervical squamous cells. In addition, its interruption by
      siRNA exhibited marked cell growth inhibition. These data indicate that
      amplification and increased expression of the Grb10 gene may play a role in the
      development of a portion of human cervical squamous cell cancer.

PMID- 15870925
TI  - Association of neuroendocrine differentiation with neoadjuvant hormone therapy
      effects in prostatic cancer.
AB  - Histological therapeutic effects of neoadjuvant hormone therapy (NHT) in
      prostatic cancer were examined, focusing on the association with neuroendocrine
      differentiation (NED), using 69 radical prostatectomy cases. The effects of NHT
      were classified into 3 grades based on the extent of tumor degeneration as
      observed with hematoxylin and eosin staining. NED cells in the cancer were semi
      quantified into 4 grades (negative, 1+, 2+, and 3+) by immunohistochemical
      staining of chromogranin A (CgA). According to the therapeutic effects, the cases
      are divided as follows: good response in 26 patients, intermediate in 20, poor in
      23. The histological therapeutic effects were significantly weaker in the CgA
      positive group than the CgA-negative group (p=0.02). A close relationship between
      the extent of CgA expression and the histological response was also demonstrated
      (p=0.007). In the biopsy specimens before NHT, CgA was positive in 46% (32/69)
      and there was no significant difference in histological therapeutic effects
      between the positive and negative groups. However, the therapeutic effects were
      significantly weaker in 22 CgA-positive cases for both biopsy and prostatectomy
      specimens than in 18 CgA-negative cases for both specimens (p=0.001). In
      conclusion, although it seems difficult to predict the therapeutic effects of NHT
      using the biopsy specimens of prostatic cancer, we believe that NED is negatively
      associated with histological response of prostatic cancer to NHT.

PMID- 15870926
TI  - Altered expression of cell cycle regulators p21, p27, and p53 in tumors of
      salivary glands and paranasal sinuses.
AB  - CIP/KIP family proteins entitled p21(WAF1/CIP1) and p27(KIP1) have key positions
      in cell cycle regulation leading to an arrest of cell proliferation. They are
      supposed to enable a repair process of DNA damage. In several human tumors, a
      loss of these proteins is associated with poor clinical outcome. The role of
      these cell cycle regulators in tumors of salivary gland and paranasal sinus
      origin is still unclear. In this study it was intended to demonstrate and compare
      the expression of p21, p27, and p53 in benign and malignant tumors of salivary
      glands and paranasal sinuses. Protein expression was detected by conventional
      immunohistochemistry (IHC). Additionally, we performed tyramide signal amplified
      immunohistochemistry (TSA-IHC) for p21 and p53 levels. Nine adenoid cystic
      carcinomas, 5 adenocarcinomas, 4 cylindrical cell carcinomas, as well as 30
      pleomorphic adenomas and 26 inverted papillomas, were studied. In 78% of all
      adenoid cystic carcinomas a complete loss of p27 expression could be identified,
      whereas 60% of the adenocarcinomas overexpressed the protein. The majority of
      cylindrical cell carcinomas showed distinct cytoplasmic accumulation of p27. All
      malignant tumors turned out to be positive for p21 after performing TSA-IHC,
      although 72% of those samples had shown weak to negative protein levels in
      conventional immunostaining. Immunohistochemical results of CIP/KIP proteins were
      compared to p53 expression as well as to main clinical parameters. The study
      sheds new light upon the role of CIP/KIP protein family in tumors of salivary
      glands and paranasal sinuses. Furthermore, it is the first description of p21 and
      p53 TSA-IHC in these tumor types.

PMID- 15870927
TI  - Effect of WNT-1 on beta-catenin expression and its relation to Ki-67 and tumor
      differentiation in oral squamous cell carcinoma.
AB  - WNT-1 has been demonstrated to play an important role in the carcinogenesis of
      some cancers, but its significance in oral squamous cell carcinoma (OSCC) has not
      yet been elucidated. We investigated the WNT-1 expression in OSCC, its role on
      the expression of beta-catenin and its relation to Ki-67 and tumor
      differentiation. Surgical specimens from 82 OSCC patients were examined for WNT
      1, beta-catenin, E-cadherin, gamma-catenin and Ki-67 expression by
      immunohistochemical staining. The results were compared with the
      clinicopathological data and the relationships were correlated. WNT-1 expression
      was low in 39 cases, moderate in 5 cases, and high in 38 cases. WNT-1 showed a
      significant association with the expression of beta-catenin, E-cadherin, gamma
      catenin and Ki-67. It was significantly correlated with tumor differentiation.
      The results of this study showed that WNT-1 expression is correlated with beta
      catenin, Ki-67 and tumor differentiation, which suggested that WNT-1 might play
      an important role in the disturbed differentiation and uncontrolled proliferation
      during OSCC carcinogenesis.

PMID- 15870928
TI  - Role of hyaluronan and hyaluronan synthase in endometrial cancer.
AB  - The aim of this study was to determine if the immunohistochemical expression of
      hyaluronan synthase (HAS) and serum levels of hyaluronan correlate with the
      clinicopathological manifestations of endometrial carcinoma. Sera were obtained
      from 59 endometrial cancer patients and 22 post-menopausal healthy women.
      Concentration of hyaluronan in sera was measured by an inhibitory ELISA using a
      hyaluronan-binding protein. Tissues obtained from 59 endometrial cancer patients
      were immunostained by the avidin-biotin-peroxidase complex method using anti
      HAS1, anti-HAS2, anti-HAS3 and anti-CD44 antibody. A section was defined as
      having positive expression when >50% of the tumor cells were intensely stained.
      The expression of HAS1 was related to the depth of myometrial invasion,
      histological grade and lymph-vascular space involvement, but the expression of
      HAS2 and HAS3 was unrelated to these parameters. CD44 expression occurred more
      frequently in the HAS2- or HAS3-positive groups than in the HAS2- or HAS3
      negative groups, and the expression of HAS1 was unrelated to CD44 expression.
      Serum levels of hyaluronan were higher in the endometrial cancer group than in
      the healthy control group, and increased with depth of myometrial invasion,
      histological grade and lymph-vascular space involvement. Serum hyaluronan levels
      were higher in the HAS1-positive group than in the HAS1-negative group, but the
      expression of HAS2 and HAS3 was unrelated to serum hyaluronan levels. HAS1
      expression and an increase in serum hyaluronan in endometrial cancer may be
      associated with disease progression through myometrial invasion and lymph
      vascular space involvement.

PMID- 15870929
TI  - A multicellular spheroid-based drug sensitivity test by scanning electrochemical
      microscopy.
AB  - The respiratory activity of a multicellular spheroid was non-invasively monitored
      by scanning electrochemical microscopy (SECM) to investigate the anticancer drug
      sensitivity. The effects of the three anticancer drugs, cisplatin (CDDP), 5
      fluorouracil (5-FU), and paclitaxel (TXL), were continuously evaluated based on
      respiratory activity for 5 days. The drug sensitivities obtained by SECM were
      higher compared to those evaluated by the spheroid volume and conformed to those
      evaluated by a conventional colorimetric assay. Our results show that the SECM
      based assay directly correlates with the number of viable cells within the
      spheroid, whereas the spheroid volume does not necessarily correlate with the
      number of viable cells. Furthermore, the results obtained by spheroid culture (3
      D) were compared to those of cells cultured in a flask (2-D) and within a
      collagen gel (3-D). The drug sensitivity of cells cultured in 2-D is more
      pronounced than that of the cells cultured in 3-D. Since the cellular
      proliferation status in a 3-D culture is similar to that in vivo, the drug
      sensitivity test performed in the spheroid culture will give meaningful results
      that can be extended to an in vivo application. A SECM-based assay is perfectly
      suitable to directly evaluate the drug sensitivity of the spheroid.

PMID- 15870930
TI  - Inhibition of cell growth and induction of apoptosis in human prostate cancer
      cell lines by 6-aminoquinolone WM13.
AB  - Fluoroquinolones affect the proliferation and apoptotic cell death of several
      human malignancies. Therefore, we investigated whether new 6-aminoquinolone
      derivatives, initially synthesized as anti-HIV agents, could affect the
      proliferation and apoptotic cell death of human prostate cancer cell lines. PC3
      and LNCaP cell lines were used as models of androgen-resistant and androgen
      responsive prostate cancer, and proliferation of PC3 and LNCaP cells was strongly
      inhibited by 6-aminoquinolone WM13. Cytotoxicity, which was more pronounced in
      LNCaP, was accompanied by morphological changes, DNA damage, arrest at the
      S/G(2)/M phase of the cell cycle, and an increase of the sub-G(1) population.
      Molecular mechanism underlying WM13-induced cell death involved caspase-8 and -3
      and modulation of the expression of apoptotic genes, as well as cleavage of poly
      ADP ribose polymerase. Cell death following the treatment of human prostate
      cancer cell lines with WM13 can be attributed to apoptosis which, depending on
      the cell line, proceeds through different pathways.

PMID- 15870931
TI  - Survivin protein in UVB induced apoptosis of melanoma cells and in melanoma
      progression.
AB  - A model system of cultivated melanoma cells and melanomas from patients were used
      in this study to clarify whether survivin protein was involved in UVB induced
      cell damage and in melanoma progression. The melanoma cells in culture were
      exposed to different doses of UVB and post-cultivated for various periods of
      time. Cell viability, apoptotic index and expression of survivin proteins were
      estimated. Expression of the survivin in normal tissue, nevi, primary and
      metastatic melanomas from the patients were also examined by
      immunohistochemistry. Results showed that UVB induced cell damage and apoptosis
      in melanoma cells. Primary and wt p53 cells were more sensitive than metastatic
      and mutant p53 melanoma cells. Expression of survivin protein was markedly
      decreased in the primary melanoma cells after exposure to UVB compared to the
      metastasis. The expression was markedly decreased in wt p53 melanoma cells, but
      not in the mutant p53 melanoma cells. Survivin protein was expressed in nevi,
      primary and metastatic melanomas. However, the normal tissues were not expressed
      in the survivin protein. Survivin plays an important role in UVB-induced
      apoptosis. Overexpression of survivin might be a biomarker for early diagnosis
      for melanoma.

PMID- 15870932
TI  - Multimodality therapy and significance of serum CYFRA21-1 for thymic carcinoma.
AB  - Thymic carcinoma is a rare mediastinal neoplasm with a poor prognosis due to
      delayed diagnosis and highly malignant behavior. To evaluate 7 serum tumor
      markers and the outcome of treatment, 11 stage III-IVb thymic carcinomas
      undergoing multimodality treatment were reviewed. High levels of serum CYFRA21-1
      were detected in 5 patients (45%) and correlated with the progression of disease.
      Of the patients, 6 underwent surgery. The median survival time was 38.4 months,
      and the 5-year survival rate was 15.6%. The metastatic stage (IVb) and treatment
      without resection were significantly associated with poorer overall survival
      (p=0.0034 and p=0.0041, respectively). Our data demonstrated that serum CYFRA21-1
      may represent a potential new biomarker in thymic carcinoma. Stage may provide a
      basis for prognosis in stage III-IVb thymic carcinoma, and resection is one of
      the most important parts of multimodality treatment for advanced thymic
      carcinoma. Effective neoadjuvant treatment is therefore essential.

PMID- 15870933
TI  - Identification and characterization of a novel kelch-like gene KLHL15 in silico.
AB  - Kelch-like proteins are implicated in embryogenesis and carcinogenesis through
      cytoskeleton organization. KLHL (kelch homolog) genes, containing two
      evolutionary conserved domains--broad-complex, tramtrack, bric-a-brac/poxvirus
      and zinc finger (BTB/POZ) domains, and kelch motif, are human homologs of
      Drosophila kelch gene. We identified the KLHL15 gene, a novel human homolog of
      Drosophila kelch, by using bioinformatics. KLHL15 gene, consisting of 4 exons,
      was located within human genome sequences RP11-47911 (AC079169.32) and RP11-793H5
      (AC079376.26). Complete coding sequence of human KLHL15 cDNA was determined by
      assembling FLJ32736 cDNA (AK057298) and KIAA1677 cDNA (AB051464). The human,
      chicken, and zebra fish KLHL15 (604 aa) showed 85-93% total-amino acid identity.
      N-terminal BTB/POZ domain and C-terminal three KELCH motifs were identified
      within KLHL15 protein by using the Pfam program. Human KLHL15 mRNA was expressed
      ubiquitously in various tissues. This is the first report on identification and
      characterization of the KLHL15 gene.

PMID- 15870934
TI  - p21Waf1/Cip1 is a common target induced by short-chain fatty acid HDAC inhibitors
      (valproic acid, tributyrin and sodium butyrate) in neuroblastoma cells.
AB  - Histone acetyltransferase and histone deacetylase (HDAC) determine the
      acetylation status of histones, and thereby control the regulation of gene
      expression. HDAC inhibitors have been found to inhibit the growth of a variety of
      tumor cells in vitro and in vivo. We demonstrated previously that the short-chain
      fatty acid compound butyrate and its derivative tributyrin (both HDAC inhibitors)
      arrest cell growth and induce differentiation in human neuroblastoma (NB) cells.
      In the current study we investigated the effect of the HDAC inhibitor valproic
      acid (VPA) on proliferation and differentiation in human NB cells (SJ-N-KP, AF8).
      Treatment with VPA resulted in a strong inhibition of cell proliferation and
      induction of cell differentiation, as revealed by neurite outgrowth and increase
      of acetylcholinesterase specific activity. Moreover, we addressed the question of
      whether the cyclin-dependent kinase inhibitors p21(Cip1) and p27(Kip1) are
      involved in the mechanism of action of members of the short-chain fatty acids
      class (VPA, sodium butyrate and tributyrin) of HDAC inhibitors, in human NB
      cells. We demonstrated that p21(Cip1) is a common target of induction of
      transcription and protein expression for all the three compounds, while only VPA
      induced a concomitant increase of p27(Kip1) gene expression. These results
      suggest that p21(Cip1) could be involved in the inhibition of proliferation and
      induction of differentiation in human NB cells induced by treatment with VPA or
      tributyrin or sodium butyrate. Moreover, p21(Cip1) could be applied in the
      molecular monitoring of drug action in the possible therapeutic application of
      these short-chain fatty acid members of HDAC inhibitors for human NB treatment.

PMID- 15870935
TI  - A phase II and pharmacologic study of fluorouracil given by a 1-hour infusion
      daily for 5 days with leucovorin and interferon alpha-2a in adenocarcinoma of the
      large bowel.
AB  - We have reported that increasing the length of infusion from 5 min to 1 h
      appeared to substantially reduce the toxicity associated with fluorouracil (5-FU)
      modulated by leucovorin (LV) and interferon alpha-2a (IFN-alpha). This phase II
      study assessed the antitumor efficacy of this regimen. Patients (n=38) with
      colorectal cancer received IFN-alpha 5 MU/m(2) SC on days 1-6; on days 2-6, LV
      200 mg/m(2) IV was given with 5-FU at initial doses of 370-425 mg/m(2)/h. The
      regimen was well-tolerated with no grade 4 toxicity. At 425 mg/m(2) 5-FU, grade 3
      toxicities included diarrhea (8.6%), anorexia, fever and fatigue (5.7% each),
      neutropenia and nausea/vomiting (2.9% each). Individuals tolerated 5-FU doses up
      to 644 mg/m(2). Objective responses occurred in 27% of 37 patients; median time
      to progression and survival were 6.1 and 12.9 months. Only 1 of 25 informative
      tumor samples had high-frequency microsatellite instability (MSI), while 7 of 23
      assessable patients (30%) with MSI-negative tumors had an objective response.
      With 425 mg/m(2), the average 5-FU Cp and AUC(0-1 h) were 37.4 microM and 1161
      microM/h. Some 6 patients had extended sampling, and the half-lives of 5-FU and
      FBAL (apparent) were 8.6 and 100.0 min, respectively. A 1-h infusion of 5-FU is
      well tolerated; individual dose escalation of 5-FU allows each patient to receive
      the maximum tolerable dose.

PMID- 15870936
TI  - Relative expression levels of Th1 and Th2 cytokine mRNA are independent
      prognostic factors in patients with ovarian cancer.
AB  - The aim of the present study was to examine mRNA expression levels of Th1 (TNF
      alpha , IFN-gamma, and IL-12p40) and Th2 (IL-6 and IL-10) cytokines for any
      association with clinicopathological characteristics of epithelial ovarian
      cancer. mRNA was isolated, and cDNA prepared from 40 samples of epithelial
      ovarian cancers. Expression level of each cytokine mRNA was examined by the real
      time PCR technique (GAPDH gene, internal control). Expression ratio (target
      gene/GAPDH) was used to evaluate gene expression. Results were analyzed against
      clinical stage, histological grade, and histological type. Prognostic
      significance of expression levels of each combination of Th1/Th2 values was
      assessed. Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN
      gamma) expression levels were significantly higher in serous adenocarcinoma than
      in non-serous adenocarcinoma (p<0.05), but with no difference between individual
      cytokine mRNA expression levels and clinical stage or histological grade. Log
      rank testing showed that high TNF-alpha mRNA expression (p=0.033) and the
      diameter of largest residual lesion at initial surgery (p=0.012) significantly
      correlate with longer survival in advanced stage (II/III/IV) ovarian carcinomas.
      In examining all combinations of Th1/Th2 expression values, the most significant
      association was between high IFN-gamma.IL-12p40/IL-6 expression levels and better
      prognosis in advanced stage (II/III/IV) ovarian carcinomas (p=0.004). In
      multivariate analysis, high IFN-gamma.IL-12p40/IL-6 expression (p=0.009) and the
      diameter of residual lesion (p=0.011) remained significantly associated with
      survival, whereas high TNF-alpha expression lost significance. In conclusion, Th1
      and Th2 cytokines might play an important role in regulating the immune reaction
      in epithelial ovarian cancer cells. IFN-gamma.IL-12p40/IL-6 expression may be a
      useful prognostic molecular marker for patients with advanced ovarian cancer.

PMID- 15870937
TI  - Efficacy of lamivudine therapy for decompensated liver cirrhosis due to hepatitis
      B virus with or without hepatocellular carcinoma.
AB  - The prognosis for patients with decompensated hepatitis B virus (HBV) related
      liver cirrhosis (LC-B), especially for those with LC-B complicated with
      hepatocellular carcinoma (HCC), is poor. We investigated the effects of
      lamivudine in patients with decompensated LC-B, with and without HCC.
      Decompensated LC-B patients (n=55) with Child-Pugh classification scores (CPS) >7
      points were enrolled. All were admitted to the hospitals of the authors between
      January 1997 and December 2004. Decompensated cases due to a severe exacerbation
      of hepatitis with CH-B and patients with HCC showing an extra hepatic metastasis
      or portal vein tumor thrombus were excluded. Some 19 cases (including 5 cases
      complicated with HCC at the start of therapy) were treated with lamivudine at 100
      mg/day (L group), and 36 (including 7 cases with HCC at time of admittance) were
      treated without lamivudine (non-L group). The median of CPS points in the L group
      was higher than that of non-L group (11 points versus 9 points, p<0.02).
      Prothrombin time (%), albumin, ascites, CPS, and HBV-DNA quantity were each
      significantly improved after 6 months in the L group (p<0.05). A mutation in the
      YMDD motif was observed in 5 patients in the L group, however liver function did
      not deteriorate. Further, the survival rate was significantly higher in the L
      group (p<0.05). HCC was found in 3 L group and 4 non-L group patients during the
      study. In the L group, all patients complicated with HCC were treated repeatedly
      or until cured, whereas 91% of those in the non-L group could not be treated
      (p<0.01). Our results suggest that lamivudine is a useful and important therapy
      for patients with decompensated LC-B with and without HCC, as well as those who
      are restricted from having liver transplantation.

PMID- 15870938
TI  - Radiation reduces pirarubicin sensitivity in human cervical squamous cell
      carcinoma cells.
AB  - To find an effective protocol for chemoradiotherapy with pirarubicin
      hydrochloride (THP) for advanced cervical cancer patients, effects of irradiation
      on THP sensitivity were examined using the radiosensitive human cervical squamous
      cell carcinoma cell line ME180. Concurrent irradiation significantly reduced THP
      sensitivity, and this was further reduced when cells were treated with THP 8 h
      after irradiation. However, the THP sensitivity of cells treated with THP 8 h
      before irradiation was significantly enhanced. Four months after the first
      irradiation, 4 subclones of ME180 cells that survived repetitive irradiation
      demonstrated significantly higher THP sensitivity than non-irradiated parent
      cells. These results indicate that THP injections, more than several hours before
      irradiation or after completion of radiotherapy, might be better therapies than
      concurrent chemoradiotherapy with THP for cervical cancer.

PMID- 15870939
TI  - [99mTc] HYNIC-hEGF, a potential agent for imaging of EGF receptors in vivo:
      preparation and pre-clinical evaluation.
AB  - Expression of epidermal growth factor receptors (EGFR) has prognostic and
      predictive value in many kinds of tumors. Imaging of expression of EGFR in vivo
      may give valuable diagnostic information. The epidermal growth factor (EGF), a
      natural ligand, is a possible candidate for the targeting of EGFR. The present
      study describes a method for preparation of (99m)Tc-EGF via the hydrazinopyridine
      3-carboxylic acid (HYNIC) conjugation using tricine and ethylenediamine-N,N'
      diacetic acid (EDDA) as co-ligands. Both conjugates bound EGFR expressing cells
      with nanomolar affinity, and demonstrated good intracellular retention. The
      complex with EDDA demonstrated much higher stability in blood serum and during
      cysteine challenge. Biodistribution of (99m)Tc-EDDA-HYNIC-EGF in normal mice
      demonstrated fast blood clearance of conjugate, and its ability to bind EGFR in
      vivo. (99m)Tc-EDDA-HYNIC-EGF is a promising candidate for visualization of EGFR
      expression in vivo.

PMID- 15870940
TI  - Radioprotective effects of various cytokines in peripheral blood mononuclear
      cells and C3H mice.
AB  - The purpose of this study was to investigate the radioprotective effect of HGFs
      (GM-CSF, IL-3 and SCF) in irradiated human peripheral blood mononuclear cells
      (PBMCs) in vitro, and the survival effect of lethally irradiated C3H mice in
      vivo. The irradiation of human PBMCs using a (137)Cs irradiator showed a dose
      dependent inhibition of cell growth up to a dose of 5 Gy. This cell growth
      inhibition induced apoptosis, which was associated with the down-regulation of
      Bcl-2, up-regulation of Bax, depolarization of mitochondrial transmembrane
      potential (Delta psi m), and caspase-3 and -9 activation. Following gamma
      irradiation at 2 Gy, IL-3 (10 ng/ml) alone or combined with SCF (50 ng/ml)
      reduced the apoptotic portion of human PBMCs by 15 and 20% of the cell
      population, respectively, showing no activation of caspase-3 compared to the
      control group. To examine the in vivo effect of gamma-irradiation and cytokines,
      we investigated the survival rate and recovery of peripheral blood cells in C3H
      mice. C3H mice subjected to total body irradiation (TBI) at a dose of 7 Gy
      (lethal dose 83% at 30 days) showed time-dependent decreases in RBC, WBC and
      platelet counts, with the nadir occurring at 12 to 15 days. However, treatment
      with recombinant murine (rm) SCF (2 microg/day s.c.), rmIL-3 (2 microg/day s.c.),
      or rmG-CSF (2.5 microg/day s.c.) 24 h before and after irradiation did not
      promote hematologic recovery or survival in the lethally irradiated C3H mice.
      These findings indicate that the combined treatment of IL-3 and SCF prevents the
      apoptosis induced in PBMCs by gamma-irradiation in vitro, but it does not afford
      any in vivo radioprotective effect in lethally irradiated C3H mice.

PMID- 15870941
TI  - The environment of increased concentration of docosahexaenoic acid in
      glioblastoma may suppress the anti-tumor effect of macrophages.
AB  - Regarding glioblastoma, there has been controversy over whether a large number of
      infiltrating macrophages act as anti-tumor effectors or not. It has been
      exhibited that intratumoral lipid environments have a possible influence on anti
      tumor immunity. Necrosis of glioblastoma and non-necrotic tissues of astrocytic
      tumors were analyzed to compare the amount of free docosahexaenoic acid (DHA)
      content. The apoptosis inducible effects of DHA on macrophages derived from
      peripheral blood monocytes and cultured glioma cells were evaluated by flow
      cytometry. The influence of DHA on the anti-tumor effects of macrophages was
      assessed at 0, 30, 60, and 90 mM of DHA by (51)Cr releasing assay and MTT assay.
      The mean concentration of free DHA in necrotic tissues (757.6 mmol/kg) was 5
      times higher than that in non-necrotic tissues (147.2 mmol/kg). The DHA
      concentration of 30 mM induced apoptosis in macrophages, however, glioma cells
      were not affected even at a DHA concentration of 60 mM. Macrophages pre-exposed
      to DHA for 24 h decreased the cytotoxicity to U251MG cells as shown by (51)Cr
      releasing assay. Total viability of co-cultured macrophages and U251MG cells
      showed an increase at high concentrations of DHA (60 and 90 mM) according to 24 h
      MTT assay, although each separate culture did not. The DHA concentration in
      necrosis of glioblastoma was sufficient for macrophages to cause apoptosis and
      suppress their anti-tumor effects. The results suggest that liberated DHA in
      necrosis can induce apoptosis in macrophages and inhibit their functions.

PMID- 15870942
TI  - Hearing loss among cancer survivors.
AB  - Cancer therapies may cause hearing loss (HL) in some patients. The purpose of
      this study is to examine at risk factors for HL and its impact on the health of a
      large cohort of cancer survivors. This is a descriptive, cross-sectional study of
      long-term cancer survivors who reported that they have experienced HL as a result
      of their cancer. Of 3571 respondents who answered a mailed survey, 243 (6.8%)
      reported HL. We analyzed the responses to discern the potential impact of
      demographics, cancer type or disease treatments on hearing, as well as the
      potential impact of HL on socioeconomic parameters (education, family and work).
      Survivors of head and neck cancer, sarcoma and testicular cancer reported HL most
      frequently. Among the younger survivors, the frequency of HL was higher than age
      matched persons from the general U.S. population. Cancer survivors with HL were
      more likely to report that cancer had affected their overall health (71 vs. 32%)
      and were unable to work. While cisplatinum exposure was noted more frequently in
      respondents with HL, no other treatments, including radiotherapy, were shown to
      have a significant impact on hearing. There were no differences with respect to
      age, gender or family dynamics. Hearing loss affects a minority of long-term
      cancer survivors and may have an impact on their education, ability to work and
      overall health.

PMID- 15870943
TI  - The cell death process of the anticancer agent polysaccharide-peptide (PSP) in
      human promyelocytic leukemic HL-60 cells.
AB  - The polysaccharide peptide (PSP) isolated from the mycelia of Chinese Medicinal
      fungus Coriolus versicolor has proven benefits in clinical trials in China but
      the mechanism of action has not been elucidated. In this study, HL-60 cell line
      was used to investigate the anti-proliferation and cell death process of PSP. The
      cytotoxicity of PSP on normal human T-lymphocytes was also evaluated. We show
      that PSP induced apoptosis of human promyelocytic leukemia HL-60 cells but not of
      normal human T-lymphocytes. The apoptotic machinery induced by PSP was associated
      with a decrease in Bcl-2/Bax ratio, drop in mitochondrial transmembrane
      potential, cytochrome c release, and activation of caspase-3, -8 and -9.
      Activation of the cellular apoptotic program is a current strategy for the
      treatment of human cancer, and the selectivity of PSP to induce apoptosis in
      cancerous and not on normal cells supports its development as a novel anticancer
      agent.

PMID- 15870944
TI  - Growth inhibition of U937 leukemia cells by aqueous extract of Cordyceps
      militaris through induction of apoptosis.
AB  - Cordyceps militaris is a traditional herbal ingredient, which has been used for
      patients suffering from cancer in Oriental medicine. In the present study, we
      investigated the biochemical mechanisms of anti-proliferative effects by aqueous
      extract of C. militaris (AECM) in human leukemia U937 cells. It was found that
      AECM could inhibit cell growth of U937 cells in a dose-dependent manner, which
      was associated with morphological change and apoptotic cell death such as
      formation of apoptotic bodies and DNA fragmentation. We observed the down
      regulation of anti-apoptotic Bcl-2 expression and proteolytic activation of
      caspase-3 in AECM-treated U937 cells. However, AECM did not affect the pro
      apoptotic Bax expression and activity of caspase-9. Furthermore, Western blotting
      and RT-PCR revealed that AECM treatment caused a dose-dependent inhibition of
      cyclooxygenase-2 and prostaglandin E2 accumulation. Taken together, these results
      indicated that the anti-proliferative effects of AECM were associated with the
      induction of apoptotic cell death through regulation of several major growth
      regulatory gene products such as Bcl-2 family expression and caspase protease
      activity, and AECM may have therapeutic potential in human leukemia treatment.

PMID- 15870945
TI  - Vasoactive intestinal peptide and pituitary adenylate cyclase activating
      polypeptide stimulate interleukin-6 production in prostate cancer cells and
      prostatic epithelial cells.
AB  - We investigated the effect of the vasoactive intestinal (VIP) and pituitary
      adenylate cyclase activating peptides (PACAP) on the production of interleukin-6
      (IL-6) in normal prostate epithelial and stromal cells and prostate cancer cells.
      We performed RT-PCR analysis to assess the expression of VIP receptor (VPAC1,
      VPAC2 and PAC1) mRNA in normal prostate epithelial and stromal cells and prostate
      cancer cells, and investigated the effect of VIP and PACAP on the production of
      IL-6. VPAC1, VPAC2 and PAC1 receptor mRNAs were expressed in LNCaP and DU-145/AR
      prostate cancer cells and PrEC cells (prostate epithelial cells). VIP stimulated
      the production of IL-6 in DU-145/AR prostate cancer and PrEC cells. PACAP showed
      a similar effect on IL-6 production in PrEC cells. VIP stimulated IL-6 promoter
      transcriptional activity in DU-145/AR cells. These results indicate that VIP and
      PACAP may modulate the IL-6 production of normal prostate epithelial and prostate
      cancer cells.

PMID- 15870946
TI  - PPP1R3 gene (protein phosphatase 1) alterations in colorectal cancer and its
      relationship to metastasis.
AB  - The PPP1R3 gene is located on chromosome 7q31, and encodes protein phosphatase 1
      (regulatory 3). It has been reported that the inactivation of various phosphatase
      proteins causes abnormalities in cell division and cell growth systems. We
      analyzed alterations in the PPP1R3 gene and its relationship to tumor progression
      and metastasis. Deletion mutants of exons containing mutations were prepared and
      assayed for intranuclear transcription activity. SSCP analysis of PPP1R3 showed
      abnormal patterns in 6 (12%) of the 50 colorectal cancers. DNA sequencing of the
      6 samples showing abnormal SSCP patterns confirmed point mutations in exon 4 in 4
      samples, and in exon 1 in 2 samples. PPP1R3 gene alterations correlated with
      lymph node and liver metastases. Enhancement of luciferase activity by the full
      PPP1R3 gene was confirmed. However, when point mutation-containing exon 1 or 4
      deletion mutants were examined for luciferase activity, enhancement of activity
      was decreased in the exon 1 deletion mutants, while no enhancement of the
      activity was noted in the exon 4 deletion mutants. These findings suggest that
      protein phosphatase 1 (regulatory 3) protein is involved in intracellular
      processes in some colorectal cancers and may play a role in metastasis.

PMID- 15870947
TI  - Defects in apoptotic signal transduction in cisplatin-resistant non-small cell
      lung cancer cells.
AB  - Non-small cell lung cancer (NSCLC) often shows intrinsic multidrug resistance,
      which is one of the most serious problems in cisplatin-based adjuvant
      chemotherapy. Anticancer drugs exert at least part of their cytotoxic effect by
      triggering apoptosis. In order to understand the molecular alterations leading to
      heterogeneous cisplatin sensitivity and apoptosis inducibility in NSCLC cells, we
      analyzed various apoptotic pathways, including the activation of caspase-8, -9
      and -3, the release of cytochrome c from mitochondria and the expression levels
      of pro- and anti-apoptotic proteins such as Bax, Bad, Bcl-2, Bcl-xL, Fas and p53
      using heterogeneously apoptosis-sensitive cells (Ma-10, Ma-31 and Ma-46).
      Cisplatin treatment induced the activation of caspase-8, -9 and -3 and the
      release of cytochrome c in apoptosis-sensitive Ma-46. The expression of Bcl-xL
      was the highest and p53 was not expressed in apoptosis-resistant Ma-31, and Fas
      was not expressed in Ma-46. These expression levels were not correlated with the
      apoptosis inducibility of the three cell lines. These results suggest that
      blockage of the apoptotic signal from mitochondria is responsible for apoptosis
      resistance in NSCLC cell lines. Our findings also indicate that anti-apoptotic
      Bcl-xL and pro-apoptotic p53 are necessary but not sufficient for resistance to
      cisplatin-induced apoptosis in NSCLC cells.

PMID- 15870948
TI  - Effects of anti-endometriotic therapies on Fas-mediated endometrial epithelial
      apoptosis.
AB  - Decreased numbers of eutopic endometrial apoptotic cells have been reported in
      endometriotic patients, indicating the possibility of anti-apoptotic effects of
      their sera. Recently, we reported that the sera from endometriotic patients
      enhance endometrial stromal cell proliferation and viability, and that Keishi
      bukuryo-gan therapy, an anti-endometriotic Japanese herbal medicine, reduces anti
      apoptotic activities in the sera. In this study, we therefore examined the
      effects of sera from 7 endometriotic patients on cell proliferation and Fas
      mediated apoptosis of the human endometrial epithelial cell line HHUA, which has
      a normal karyotype and functional estrogen and progesterone receptors. Cell
      proliferation was not affected by any of the sera examined, including sera from
      healthy women. The sera of 6 out of 7 endometriotic patients and sera from 2
      healthy women significantly inhibited Fas-mediated apoptosis in the cells.
      Moreover, anti-apoptotic activities in the sera of endometriotic patients on Fas
      mediated apoptosis were not affected by gonadotropin-releasing hormone agonist
      (GnRHa) therapy within 4 weeks or Keishi-bukuryo-gan therapy within 12 weeks.
      Considering these results, we suggest that the surviving factor(s) against Fas
      mediated endometrial epithelial cell apoptosis in human sera can be found in
      endometriotic and non-endometriotic women, and that decreased eutopic endometrial
      epithelial apoptosis in endometriotic patients might be caused by the secondary
      effects of endometrial stromal cell growth and surviving factor(s) in sera of the
      patients, not by direct serum effects on the epithelium.

PMID- 15870949
TI  - Overexpression of survivin mRNA is associated with a favorable prognosis
      following neoadjuvant radiochemotherapy in esophageal cancer.
AB  - Survivin is a member of the inhibitor of apoptosis (IAP) gene family known to be
      involved in resistance to chemo- and radiation therapy. We examined the potential
      of quantitative survivin mRNA expression to predict histopathologic tumor
      response and prognosis following neoadjuvant radiochemotherapy (cis-platinum, 5
      FU, 36 Gy) in patients with locally-advanced esophageal cancer (cT2-4, Nx, M0).
      Tumor (T) and normal tissue (N) samples from 51 patients were collected by
      endoscopic biopsy prior to treatment. Survivin mRNA expression was analyzed by
      quantitative real-time RT-PCR assays. Histomorphologic regression was defined as
      a major response when resected specimens contained <10% of residual vital tumor
      cells or if a pathologically complete response was achieved. Some 7/51 patients
      had progressive disease and 44/51 proceeded to surgical resection. Of 44 resected
      tumors, 17 (31.4%) showed a major and 27 (61.4%) showed a minor histopathologic
      response; the survival rates were significantly different (p<0.01). Median
      absolute survivin expression was 5.1 in the tumor and 2.4 in corresponding normal
      tissue samples (Wilcoxon, p<0.001). Median relative (T/N ratio) survivin mRNA
      expression was 1.7. Survivin mRNA expression levels did not show a significant
      association with histomorphologic regression. Relative survivin mRNA expression
      of a T/N ratio >1 indicated a favorable prognosis (log-rank, p<0.003). Expression
      levels of survivin mRNA in pretherapeutic biopsies did not predict the extent of
      histomorphologic tumor regression following preoperative radiochemotherapy for
      esophageal cancer. However, overexpression of survivin mRNA in pretreatment
      biopsies (T/N ratio >1) was associated with superior survival probabilities.

PMID- 15870950
TI  - Restoration of connexin 43 by Bowman-Birk protease inhibitor in M5076 bearing
      mice.
AB  - The present study was designed to investigate the effects of Bowman-Birk
      inhibitor (BBI) on up-regulation of connexin (Cx) expression to estimate BBI's
      tumor-suppressor effect in mice with M5076 ovarian sarcoma. The relative tumor
      weight (p<0.05, r(2)=0.301) and proliferating cell nuclear antigen (PCNA, p<0.01,
      r(2)=0.493) were negatively correlated with the doses of BBI. In contrast, the
      relative density of Cx43 was positively correlated with the doses of BBI (p<0.05,
      r(2)=0.351). Therefore, it suggests that the anti-carcinogenic effects of BBI
      induced negative growth control caused by the expression of Cx43 genes in mice
      with M5076 ovarian sarcoma.

PMID- 15870955
TI  - The regulation of embryonic patterning and DNA replication by geminin.
AB  - Geminin is a multifunctional protein. After DNA replication is initiated during a
      cell cycle, geminin binds to Cdt1, one of the key DNA replication licensing
      factors. This highly regulated interaction sequestrates Cdt1, thus preventing DNA
      rereplication in the same cell cycle. In addition, geminin directly interacts
      with Six3 and Hox homeodomain proteins during embryogenesis and inhibits their
      functions. The regulation of Hox function by geminin also involves a transient
      association with the Hox repressive Polycomb complex. The functions of geminin to
      obstruct key molecules of both cell proliferation and embryonic development
      suggest a competitive coordination of these two processes.

PMID- 15870954
TI  - Ethanol inhibits insulin expression and actions in the developing brain.
AB  - Ethanol-induced cerebellar hypoplasia is associated with inhibition of insulin
      stimulated survival signaling. The present work explores the mechanisms of
      impaired insulin signaling in a rat model of fetal alcohol syndrome. Real-time
      quantitative RT-PCR demonstrated reduced expression of the insulin gene in
      cerebella of ethanol-exposed pups. Although receptor expression was unaffected,
      insulin and insulin-like growth factor (IGF-I) receptor tyrosine kinase (RTK)
      activities were reduced by ethanol exposure, and these abnormalities were
      associated with increased PTP1b activity. In addition, glucose transporter
      molecule expression and steady-state levels of ATP were reduced in ethanol
      exposed cerebellar tissue. Cultured cerebellar granule neurons from ethanol
      exposed pups had reduced expression of genes encoding insulin, IGF-II, and the
      IGF-I and IGF-II receptors, and impaired insulin- and IGF-I-stimulated glucose
      uptake and ATP production. The results demonstrate that ethanol inhibits insulin
      mediated actions in the developing brain by reducing local insulin production and
      insulin RTK activation, leading to inhibition of glucose transport and ATP
      production.

PMID- 15870956
TI  - Regional differences of superoxide dismutase activity enhance the superoxide
      induced electrical heterogeneity in rabbit hearts.
AB  - During myocardial ischemia and the subsequent reperfusion, free radicals are
      important intermediates of the cellular damage and rhythm disturbances. We
      examined the effects of superoxide radicals or hydrogen peroxide (H(2)O(2)) on
      the action potentials in isolated rabbit Purkinje fibers, atrial muscle and
      ventricular muscle. Reactive oxygen species (ROS) donors such as adriamycin,
      xanthine/xanthine oxidase and menadione induced prolongation of APD(90) in
      Purkinje fibers. Menadione (30 microM), the most specific superoxide radical
      donor, prolonged the action potential duration at 90% repolarization (APD(90)) by
      17% in Purkinje fibers, whereas it shortened the APD by 57% in ventricular
      muscle, and it did not affect the atrial APD. All these menadione-induced effects
      were completely blocked by 2,2,6,6-tetramethyl- 1-peperadinyloxy, a superoxide
      radical scavenger. Superoxide dismutase (SOD) activity was lowest in Purkinje
      fibers, it was moderate in atrial muscle and highest in ventricular muscle.
      H(2)O(2) shortened the APDs of all three cardiac tissues in a concentration
      dependent manner. These results suggest that the different electrical responses
      to O(2) ([Symbol: see text]-) in different cardiac regions may result from the
      regional differences in the SOD activity, thereby enhancing the regional
      electrical heterogeneity.

PMID- 15870957
TI  - Re: "Interstitial recurrence, with chronic inguinodynia, after Lichtenstein
      herniorrhaphy" by Drs. Raymond Read and Arthur Gilbert"--Hernia (2004) Volume 8,
      Issue 3, pp. 264-267.

PMID- 15870959
TI  - Can aesthetic facial reconstruction be judged in black and white?
AB  - Aesthetic considerations of the face need to be evaluated in real-life full
      color. Staged contouring and insetting of a transferred free flap is sometimes
      required. This consists of debulking, thinning, and reshaping the flap. If the
      facial area is involved, however, color mismatch of a free flap represents an
      aesthetic challenge for the reconstructive surgeon, and often is missed with
      black and white photos. This article reports on a patient in whom a first dorsal
      metatarsal cutaneous free flap was used to reconstruct a full-thickness defect in
      the lateral orbit including upper and lower eyelids and outer canthus. The flap
      resulted in an unacceptable aesthetic outcome consisting of a bulky,
      hypopigmented deformity. Revisional surgery consisted of debulking the free flap
      and resurfacing it with a full-thickness skin graft taken from the postauricular
      area. This resulted in a pleasant, thin, and better color match reconstruction.
      The advantages of the first web space of foot free flap to the eyelid are well
      described. The authors are of the opinion that the flap does not match the color
      of the eyelid region, and therefore suggest that if used, prefabrication or a
      second procedure is needed. Evaluation of the postoperative results needs to be
      in color because black and white can mask the final aesthetic result.

PMID- 15870960
TI  - Liposuction "conscious sedation" monitored anesthesia care and level of
      consciousness monitoring.

PMID- 15870961
TI  - The fate of intramuscularly injected fat autografts: an experimental study.

PMID- 15870962
TI  - Morphology of the gluteal region in the female population 5 to 83 years of age.
AB  - This study evaluated the development of gluteal region morphology in the female
      population 5 to 83 years of age. For the study, 132 female subjects were placed
      into four groups: prepubertal (ages 5 to 8 years; n = 10), pubertal (ages 9 to 14
      years; n = 38) postpubertal (ages 15 to 41 years; n = 34), and menopausal
      postmenopausal (older than 42 years; n = 29). The age, weight, and height of the
      subjects were routinely recorded, and body mass index was estimated. In addition,
      11 measurements were performed on the gluteal region. The data were analyzed by
      Pearson and Spearmen correlation analyses using SSPS 11.0 for Windows. In the
      prepubertal group, the intergluteal sulcus and infragluteal sulci did not
      actively change. Weight gain was the major factor influencing the shape of the
      gluteal region, whereas age had no effect. In the puberty group, the gluteal
      region expanded in all directions. During this period, it was difficult to
      determine any specific relation between measurements because of significant
      correlation involving all parameters. However, it should be mentioned that among
      the four groups, only in pubertal group did age significantly affect the shape of
      the gluteal region. In other three groups, weight seemed to be a major
      determinant. In the pospubertal and menopausal-postmenopausal groups, the
      buttocks sagged with weight gain, contrary to the belief that this happens with
      aging. This causes movement of the infragluteal sulci in downward and lateral
      directions as well as lengthening of intergluteal sulcus. Although the gluteal
      shape is open to the effects of demographic factors such as ethnicity, feeding
      habits, and lifestyle, according to these findings, it might be advised that in
      the assessment of the gluteal region morphology, it would be better to consider
      its dynamic nature. Reshaping its only one part, which can be devastating unless
      the whole gluteal region and upper limb are addressed.

PMID- 15870963
TI  - Prilocaine plasma levels and methemoglobinemia in patients undergoing tumescent
      liposuction involving less than 2,000 ml.
AB  - BACKGROUND: As a reaction to reported adverse outcomes after lidocaine
      infiltration in tumescent liposuction, prilocaine has gained increasing
      popularity. Previous studies investigating large-volume liposuction procedures
      found maximum prilocaine levels and methemoglobinemia up to 12 h postoperatively,
      suggesting that liposuction should be performed as a hospital procedure only. The
      aim of this study was to determine prilocaine plasma levels and methemoglobinemia
      in patients after low- to average-volume liposuction for the purpose of defining
      the required postoperative surveillance period. METHODS: In 25 patients
      undergoing liposuction involving less than 2,000 ml prilocaine levels and
      methemoglobinemia were measured over 4 h postoperatively. Liposuction was
      conducted after the tumescent technique using a 0.05% hypotonic prilocaine
      solution with epinephrine. RESULTS: The average prilocaine dose was 6.8 + 0.8
      mg/kg, with a maximum dose of 15 mg/kg. The peak prilocaine plasma level of 0.34
      mug/ml occurred 3 h after the infiltration. The mean methemoglobinemia at this
      time point was 0.65%. Only one patient demonstrated a slightly elevated
      methemoglobin level of 1.4%, but lacked any clinical signs of methemoglobinemia.
      The prilocaine recovery in the aspirate averaged 36 +/- 4%, indicating that a
      large amount is removed by suctioning. CONCLUSIONS: The patients did not
      experience high plasma levels of prilocaine or methemoglobinemia undergoing
      liposuction involving less than 2,000 ml using a 0.05% hypotonic prilocaine
      solution. The authors therefore conclude that this procedure can be performed
      safely with a monitoring period of 12 h.

PMID- 15870964
TI  - Assessment of the physical properties of laparoscopic myoma-fixation devices.
AB  - BACKGROUND: The physical properties of three commercial 5-mm myoma-fixation
      devices available for clinical use (short-pitch corkscrew, long-pitch corkscrew,
      buttress-thread screw) and a standard wood screw were examined. METHODS: Fresh
      specimens of uterine leiomyoma masses were used to test the maximum traction
      force obtained from each device on 31 occasions. The myoma tissue at each
      traction site was evaluated histologically to determine its density. The maximal
      traction forces in each myoma density group were compared using a generalized
      estimating equations approach to linear regression based on repeated measures
      within each myoma. The bending strength also was determined for each device.
      RESULTS: A wide range of maximum traction forces with a mean of 130.8 +/- 71.5 N
      (range, 21.6-341.6 N) over all devices and tissue densities was recorded. The
      mean maximum traction force provided by the short-pitch corkscrew (159.2 +/- 12.2
      N) was significantly higher (p < 0.01) than that of the other devices in medium
      density myomas, and not significantly lower than that of other devices in low
      density myomas. The mean maximum traction force provided by the buttress-thread
      screw was significantly lower than that of the short-pitch corkscrew only in
      medium density myomas, and did not differ significantly from that of the wood
      screw in any density group. The wood screw provided the highest bending strength
      (6.73 x 10(4) N/m) (whereas the short- and long-pitch corkscrew provided the
      lowest (9.70 x 10(2) N/m and 1.95 x 10(3) N/m, respectively) and the buttress
      thread screw an intermediate (2.24 x 10(4) N/m) strength (p < 0.0005 for all
      comparisons except for the two corkscrews). CONCLUSIONS: Screw-type myoma
      fixation devices can provide comparable traction force with high bending
      strength. A long-pitch corkscrew should not be used for laparoscopic myomectomy
      because of its low traction force and bending strength. When a commercial screw
      is not available, a standard wood screw can be used with acceptable traction
      force and very high strength for bending.

PMID- 15870965
TI  - Impact of taurolidine on the growth of CC531 coloncarcinoma cells in vitro and in
      a laparoscopic animal model in rats.
AB  - BACKGROUND: The object of this study was to examine the effect of taurolidine on
      intraabdominal tumor growth in a laparoscopic animal model. We tested the
      cytotoxic, antiadhesive, and anti-invasive effects of this substance on CC531
      adenocarcinoma cells in vitro and in vivo using WAG rats. METHODS: For in vitro
      experiments, Transwell dual chambers with polycarbonate filters coated with 100
      microg/cm2 Matrigel were used to investigate the effects of 5, 10, and 20 microl
      of 2.0% taurolidine on the invasion of 1 x 10(5) CC531 adenocarcinoma cells. For
      the adhesion assays, tumor cells were applied onto microtiter plates coated with
      5, 10, and 20 microl taurolidine and 0.9% NaCl solution for the control group
      subsequently. For in vivo experiments, 40 WAG rats were randomized into three
      therapy groups and one control group. All animals underwent laparoscopy and
      received 1 ml of CC531 adenocarcinoma cells (5 x 10(6) cells/ml) intraabdominally
      at the beginning of the procedure. According to the randomization, the rats were
      administered taurolidine with different concentrations or 1 ml of 0.9% NaCl
      solution for the control group. After 21 days, the animals were killed and the
      intraabdominal tumor weight was determined. RESULTS: For the in vitro
      experiments, we found a moderate cytotoxicity and a significant inhibition of
      tumor cell adhesion and invasion (p < 0.01) by all taurolidine concentrations
      used in the assay. For in vivo experiments, the application of all concentrations
      of taurolidine significantly decreased the intraperitoneal tumor weight (p <
      0.001). CONCLUSION: Taurolidine significantly decreases adhesion and invasion of
      CC531 adenocarcinoma cells in vitro and significantly diminishes tumor growth in
      vivo. This may offer additional therapeutic options for laparoscopic surgery for
      colorectal cancer.

PMID- 15870967
TI  - Japan's silver human resource centers and participant well-being.
AB  - Japan's Silver Human Resource Center (SHRC) program provides part-time, paid
      employment to retirement-aged men and women. We studied 393 new program
      participants and examined whether part-time work influenced their well-being or
      "ikigai." The participants were divided into those who had worked in SHRC
      provided jobs in the preceding year, and those who had not. Gender-stratified
      regression models were fitted to determine whether SHRC employment was associated
      with increased well-being. For men, actively working at a SHRC job was associated
      with greater well-being, compared to inactive members. And men with SHRC jobs and
      previous volunteering experience had the greatest increase in well-being. Women
      SHRC job holders did not experience increased well-being at the year's end. The
      study concludes that there is justification for exploring the usefulness of a
      similar program for American retirees who desire post-retirement part-time work.

PMID- 15870968
TI  - Growing old in St. Lucia: expectations and experiences in a Caribbean village.
AB  - In St. Lucia there are increased proportions of elders secondary to decreasing
      fertility and mortality rates and increasing life expectancy. The fact that
      people are living longer is a reflection of social success; however, increasing
      numbers of elders (often with chronic health problems) challenge family, social,
      health, political, and economic systems. Who will provide care and how this care
      will be provided are at the forefront of health and social service planning and
      debate. This paper describes the status of elders in St. Lucia. Expectations as
      well as current care experiences of elders and villagers are described.

PMID- 15870969
TI  - Epithelial cell turnover in relation to ongoing damage of the gastric mucosa in
      patients with early gastric cancer: increase of cell proliferation in
      paramalignant lesions.
AB  - BACKGROUND: Gastric cancer is typically an end result of Helicobacter pylori
      associated chronic gastritis. The pathogenesis is thought to involve effects on
      gastric mucosal epithelial cell turnover. In this study, we aimed to compare
      apoptosis and proliferation in the noncancer-containing mucosa of H. pylori
      positive patients with early gastric cancer with these phenomena in H. pylori
      positive controls. METHODS: Two specimens each were obtained from the greater and
      lesser curvatures of the corpus and from the greater curvature of the antrum. The
      histopathological grading used was the updated Sydney System. Apoptotic
      epithelial cells were detected using the terminal deoxy nucleotidyl transferase
      mediated deoxy-uridine triphosphate (dUTP) biotin nick-end labeling (TUNEL)
      method. The expression of Ki 67 was evaluated by immunostaining. RESULTS: Forty
      five H. pylori-positive patients with endoscopic mucosal resection for early
      gastric cancer and 52 H. pylori-positive controls were studied. Gastric cancer
      was associated with a higher frequency of incomplete intestinal metaplasia (IM;
      odds ratio [OR], 19.1; 95% confidence interval [CI], 6.9-53.2; P < 0.001). The
      apoptotic index (AI) in the greater curvature of the corpus and the proliferation
      index (PI) in each part were significantly higher in cancer patients than in the
      control group. The median PI in the antrum was significantly higher in the
      incomplete IM group than that in the complete IM group (17.6 vs 12.6; P = 0.009).
      The PI and the AI in the greater curvature of the corpus correlated with the
      activity score, and the PI correlated with the IM score. CONCLUSIONS: In the
      cancer patients, H. pylori-induced gastritis was associated with increased cell
      proliferation and apoptosis compared with mucosal findings in the controls. IM
      seems to be one of the most important factors affecting cell proliferation and
      may be one of the components of carcinogenesis that results in proliferation
      dominant cell kinetics.

PMID- 15870970
TI  - Distribution of ghrelin-immunoreactive cells in human gastric mucosa: comparison
      with that of parietal cells.
AB  - BACKGROUND: Ghrelin is a novel 28-amino-acid peptide isolated from rat and human
      stomach. This peptide is an endogenous ligand for the growth hormone secretagogue
      receptor and stimulates the release of growth hormones. Although the principal
      site of ghrelin synthesis has been reported to be in the stomach, there have been
      no reports of detailed descriptions of the distribution of ghrelin-immunoreactive
      cells in the stomach. We examined the distribution of ghrelin-immunoreactive
      cells in human gastric mucosa. METHODS: We studied the tumor-free mucosa along
      the lesser curvature in 30 patients with gastric cancer. Sections were stained
      with hematoxylin and eosin and then subjected to ghrelin immunohistochemistry.
      The distribution of ghrelin-immunoreactive and parietal cells was studied by
      continuous cell counting in restricted fields along the lamina muscularis mucosa.
      RESULTS: Ghrelin-immunoreactive cells were found in all regions, but were
      distributed mainly in the fundic region. The distribution of ghrelin
      immunoreactive cells was positively correlated with that of parietal cells.
      CONCLUSIONS: The results of this study suggested that the distribution of ghrelin
      immunoreactive cells follows that of parietal cells.

PMID- 15870971
TI  - Influence of cure of Helicobacter pylori infection on gastric acidity and
      gastroesophageal reflux: study by 24-h pH monitoring in patients with gastric or
      duodenal ulcer.
AB  - BACKGROUND: Whether or not the eradication of Helicobacter pylori is a risk
      factor for reflux esophagitis (RE) is a question at issue. To find an answer, it
      is necessary to clarify the influence of H. pylori eradication on the mechanism
      of RE. METHODS: The authors investigated the influence of H. pylori eradication
      on gastric acidity and gastroesophageal reflux in ten gastric ulcer (GU) patients
      and ten duodenal ulcer (DU) patients by 24-h simultaneous determination of pH in
      the stomach and esophagus. RESULTS: Though the results indicated enhanced gastric
      acidity in GU patients at night after H. pylori eradication, no such influence
      was observed in DU patients. No significant changes in gastroesophageal reflux
      occurred in GU or DU patients before and after H. pylori eradication. RE after H.
      pylori eradication occurred in only one patient, with GU. This patient had
      several risk factors for RE, such as obesity, male sex, and dietary habits to add
      to the increase in gastric acidity at night that occurred after H. pylori
      eradication. No increase in gastroesophageal reflux occurred in any DU patients
      or in the other GU patients that demonstrated enhanced gastric acidity at night
      after H. pylori eradication. CONCLUSIONS: The cure of H. pylori infection does
      not, by itself, cause RE in patients who have few other risk factors for RE.

PMID- 15870972
TI  - Lyprinol (stabilised lipid extract of New Zealand green-lipped mussel): a
      potential preventative treatment modality for inflammatory bowel disease.
AB  - BACKGROUND: Lyprinol (Pharmalink International), the stabilised lipid extract of
      the New Zealand green-lipped mussel, is currently used to relieve symptoms of
      arthritis. We investigated the effect of pretreatment with Lyprinol (LYP) on
      experimentally induced inflammatory bowel disease (IBD) in mice. METHODS: Male
      C57BL/6 mice (aged 6 weeks) were gavaged daily for 13 days with (150 microl)
      olive oil (OO; n = 7), fish oil (FO; n = 8), or LYP (n = 8). Mice consumed 2%
      dextran sulfate sodium (DSS) for 6 days, starting on day 7. Body weight and
      disease activity index (DAI) scores were recorded daily. Colonic damage was
      determined by histopathology. Colonic inflammation was quantified by
      myeloperoxidase (MPO) activity. RESULTS: LYP treatment significantly (P < 0.05)
      reduced body weight loss, DAI scores, crypt area losses, and cecum and colon
      weights, compared with FO treatment. MPO activity was not significantly affected
      by any treatment. CONCLUSIONS: These findings provide preliminary evidence that
      Lyprinol may be potentially useful in ameliorating symptoms of IBD. The benefit,
      however, is unlikely to be due to the omega-3 fatty acid content. Dose-response
      evaluation of Lyprinol in experimental IBD is warranted.

PMID- 15870973
TI  - Mutational analysis of the MRP2 gene and long-term follow-up of Dubin-Johnson
      syndrome in Japan.
AB  - BACKGROUND: Recent studies have indicated that dysfunction or loss of the
      multidrug resistance protein 2 (MRP2) is the molecular basis of Dubin-Johnson
      syndrome (DJS). To clarify the genetic basis of the disease and the long-term
      stability of serum bilirubin levels, we conducted a mutational analysis of the
      MRP2 gene and followed up serum bilirubin levels in Japanese DJS patients 30
      years after they were originally diagnosed, based on traditional criteria.
      METHODS: Patients were interviewed by telephone, and blood tests, including a
      genetic analysis of MRP2, were performed on the patients and family members who
      gave informed consent. RESULTS: Over the 30 years, hyperbilirubinemia remained
      unchanged in four of the five patients studied, while it worsened in 1 patient
      whose DJS was complicated by chronic hepatitis C. From an MRP2 gene mutational
      analysis, six mutations, including the novel mutation 1177C>T, were found. Three
      patients of a consanguineous family were homozygotes for three mutations (298C>T,
      1967+2T>C, and 2439+2T>C). Two patients were compound heterozygotes
      (1177C>T/2302C>T and 1967+2T>C/2026G>C). A familial study showed no difference in
      serum bilirubin levels between mutant/wild heterozygotes and wild/wild
      homozygotes. CONCLUSIONS: The hyperbilirubinemia of four Japanese patients with
      DJS, one of whom had a novel mutation, 1177C>T, of the MRP2 gene, had not
      worsened with aging.

PMID- 15870974
TI  - Superparamagnetic iron oxide-enhanced MR imaging for focal hepatic lesions: a
      comparison with CT during arterioportography plus CT during hepatic
      arteriography.
AB  - BACKGROUND: We aimed to evaluate the efficacy of a breath-hold superparamagnetic
      iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging protocol for the
      detection of focal hepatic lesions, in comparison with a non-breath-hold SPIO
      enhanced imaging protocol and computed tomography during arterioportography
      (CTAP) plus CT during hepatic arteriography (CTHA). METHODS: Findings of SPIO
      enhanced MR imaging and CTAP/CTHA for 24 hepatic metastases in 17 patients and 29
      HCCs in 21 patients were analyzed. All patients underwent breath-hold SPIO
      enhanced MR imaging (1.5 tesla), breath-hold plus non-breath-hold SPIO-enhanced
      MR imaging, and CTAP plus CTHA prior to partial hepatectomy or laparoscopic
      ablation therapy. Histopathology for lesion characterization and intraoperative
      ultrasound for lesion detection were available for all patient. Breath-hold SPIO
      enhanced MR imaging consisted of T2-weighted single-short fast spin echo (FSE),
      T2-weighted (T2W) FSE, T2*-weighted gradient echo (GRE), and T1-weighted GRE. For
      the non-breath-hold imaging protocol, respiratory-triggered, fat-suppressed T2W
      FSE was added to the breath-hold MR imaging protocol. Double phase CTAP plus CTHA
      was performed on an angio-CT system. To compare the three imaging protocols,
      three radiologists performed blind film reading, and all data, on a hepatic
      segment-to-segment basis, were entered for alternative free-response receiver
      operating characteristic (AFROC) analysis. RESULTS: ROC analysis showed that
      there was no significant difference in the area under the AFROC curve (A1) value
      for metastases and HCCs among the three protocols; the breath-hold SPIO-enhanced
      MR imaging protocol, non-breath-hold MR imaging protocol, and CTAP plus CTHA. The
      breath-hold SPIO-enhanced MR imaging protocol showed a sensitivity, specificity,
      and accuracy equivalent to the non-breath-hold MR imaging protocol and CTAP plus
      CTHA. CONCLUSIONS: As a preoperative test, SPIO-enhanced MR imaging could have
      the potential to replace CTAP plus CTHA in a certain clinical setting.

PMID- 15870975
TI  - Duodenum is important for the sphincter of Oddi motor response to cholecystokinin
      octapeptide in conscious dogs.
AB  - BACKGROUND: We investigated the role of the duodenum in the sphincter of Oddi
      response to cholecystokinin-octapeptide (CCK-OP), using conscious dogs. METHODS:
      In controls, a cannula was inserted into the duodenum opposite the papilla for
      retrograde manometry. In the duodenectomy group, the entire duodenum was
      resected, while preserving the papilla, which was implanted into the jejunum, and
      the cannula was placed. Sphincter motility was recorded after bolus injections of
      20 and 100 ng/kg of CCK-OP. RESULTS: CCK-OP at 20 ng/kg produced sphincter
      relaxation followed by contraction in the controls, but produced no changes after
      duodenectomy. CCK-OP at 100 ng/kg caused strong contractions followed by
      relaxation in the controls, but caused only contractions after duodenectomy.
      CONCLUSIONS: (1) Relaxation and delayed contraction of the sphincter induced by
      20 ng/kg of CCK-OP require the presence of the duodenum; (2) early contractions
      of the sphincter induced by 100 ng/kg of CCK-OP do not require the duodenum; (3)
      the duodenum plays an important role in the actions of CCK-OP on sphincter
      motility.

PMID- 15870976
TI  - A high peripheral microvessel density count correlates with a poor prognosis in
      pancreatic cancer.
AB  - BACKGROUND: Microvessel density (MVD) has been shown to be associated with a poor
      prognosis in gastric, colorectal, breast, and lung cancers. However, there are
      few positive results in pancreatic cancer. We hypothesized that high counts of
      MVD, determined by the lumen method as compared with the hot-spot method, would
      show a significant correlation with a poor prognosis in pancreatic cancer.
      METHODS: Thin slices from the center and periphery of 41 resected pancreatic
      tumors were immunostained with factor VIII monoclonal antibody. MVD was
      determined under high magnification by the lumen method, which counts only those
      structures showing vessel formation positive for factor VIII. The relationship
      between MVD and clinical and histological variables and the development of liver
      metastases and survival was assessed with logistic and Cox regression analyses,
      respectively. RESULTS: Liver metastasis developed in 22 patients (54%) after
      surgery. Peripheral MVD, as measured by the lumen method, and N-category (TNM
      classification) were both significantly associated with liver metastasis.
      Survival rates were 50%, 15%, and 10% for 1, 3, and 5 years, respectively. Poor
      survival was significantly associated with male sex; high peripheral MVD, as
      measured by the lumen method; arterial invasion; and T-category ranking (TNM
      classification). CONCLUSIONS: High peripheral MVD, as assessed by the lumen
      method, is associated with the occurrence of liver metastasis and with a poorer
      prognosis in pancreatic cancer.

PMID- 15870977
TI  - Spontaneous remission of primary diffuse large B-cell gastric lymphoma.
AB  - Spontaneous and complete disappearance of diffuse large B-cell lymphoma (DLBL) of
      the stomach is extremely rare. Although regression of gastric DLBL after
      eradication of Helicobacter pylori has recently been reported, we present two
      consecutive cases of stage I DLBL of the stomach which disappeared after only
      nonspecific therapy, including histamine 2-receptor antagonist (H2RA); both cases
      were documented histologically and endoscopically. Both patients were positive
      for H. pylori, and later received H. pylori eradication therapy. The disease has
      not recurred after 11 and 6 months, respectively. Our cases suggest that the
      option of combination therapy with H2RA either with or followed by H. pylori
      eradication is appropriate for consideration as an initial approach in standard
      therapy for stage I diffuse large B-cell gastric lymphoma.

PMID- 15870978
TI  - Monozygotic twins concordant for intestinal Behcet's disease.
AB  - Although Behcet's disease (BD) is a multisystem disorder of unknown causes, both
      genetic and environmental factors have been suggested. This is the second
      reported case of monozygotic twins concordant for Behcet's disease and the first
      such report of intestinal Behcet's disease. Patient 1 was a 17-year-old man with
      fever, recurrent oral aphthae, and skin eruptions. He developed hematochezia and
      was given corticosteroid empirically. One month after he was discharged, he again
      developed oral ulcerations, fever, and hematochezia. Colonoscopy was performed
      again, showing aphthous ulcerations in the entire colon, and deep oval ulcers
      with marginal elevation around the ileocecal valve, which are characteristics of
      intestinal Behcet's disease. He was treated with colchicine and azathioprine in
      combination with salazosulfapyridine (SASP) and prednisolone (PSL) and achieved
      remission. Patient 2 was the twin brother of patient 1. He was admitted because
      of oral aphthous ulcerations, fever, pustules on his face and body, and genital
      ulcers. Two weeks later he developed hematochezia. Colonoscopic and barium enema
      findings were similar to those of his brother. SASP, PSL, colchicines, and
      azathioprine were also required to achieve remission. Both of the patients were
      diagnosed with intestinal Behcet's disease. Their monozygosity was confirmed by
      detailed genetic typing, and HLA-B51 was negative.

PMID- 15870979
TI  - Usefulness of recombinant Em18-ELISA to evaluate efficacy of treatment in
      patients with alveolar echinococcosis.
AB  - Alveolar echinococcosis (AE) is a rare parasitic disease caused by Echinococcus
      multicularis and most commonly involves the liver. Early diagnosis is essential
      to improve the prognosis of patients with AE of the liver. Em18, an 18-kD
      diagnostic antigen from Echinococcus multilocularis, is highly specific and
      sensitive to detect AE. We previously reported that an enzyme-linked
      immunosorbent assay (ELISA) system using a recombinant Em18 antigen (RecEm18) was
      highly useful in the differential serodiagnosis of AE. In this report, we present
      seven AE patients who showed dynamic changes in RecEm18-ELISA values in the
      course of long-term follow up of albendazole (ABZ) chemotherapy, and/or
      resections of the liver or bone metastasis. All seven AE patients revealed
      positive values, over the cutoff level, of the RecEm18-ELISA before the
      treatments. The values in six patients fell below the cutoff level after the
      treatments, but the value in a patient with recurrence never fell below the
      cutoff level, and increased again. From these results, it seems that the RecEm18
      ELISA is useful to evaluate the efficacy of treatment and predict recurrence in
      patients with AE. RecEm18-ELISA may be an important examination for: (a) the mass
      screening of AE in Japan, (b) the confirmative diagnosis of AE prior to surgical
      and/or chemotherapeutic treatments, (c) the follow up of AE patients after
      treatments, and (d) for deciding on the discontinuation of chemotherapy in
      patients with an appropriate response.

PMID- 15870980
TI  - Des-gamma carboxy prothrombin (PIVKA-II)- and alpha-fetoprotein (AFP)-producing
      gastric cancer.

PMID- 15870981
TI  - Refractory enterovesical and duodenocolic fistulas in Crohn's disease
      successfully managed with tacrolimus.

PMID- 15870982
TI  - Need for etiological classification of chronic pancreatitis.

PMID- 15870983
TI  - Structural characteristics of video lotteries: effects of a stopping device on
      illusion of control and gambling persistence.
AB  - Two studies investigated the effects of a video lottery terminal stopping device
      on gamblers' thoughts and behavior. This structural characteristic allows players
      to voluntarily stop the spinning of the reels. The first study investigated the
      effect of this device on the development of illusions of control. It was
      predicted that players using the stopping device would believe that (1) symbols
      displayed could differ depending on when the game is stopped, (2) there is a
      possibility of controlling the outcome of the game, (3) skills may be a factor
      influencing the results, and finally (4) a stopping device would improve the
      probability of personal success (i.e., developing the illusion of control). The
      second study aimed to further evaluate the effects of the stopping device on
      gambling behavior. It was hypothesised that using the stopping device would
      encourage players to increase the number of games played in a session. Results
      confirmed all predictions and showed that offering a stopping device on video
      lottery terminals modifies gamblers' cognition and behavior. The theoretical and
      practical implications of these results are discussed in the context of
      responsible gambling policies.

PMID- 15870984
TI  - Motivators for change and barriers to help-seeking in Australian problem
      gamblers.
AB  - Although prevalence studies consistently indicate that many thousands of
      Australians experience gambling-related problems, only a relatively small
      proportion of these people seek professional help. This study examines the
      principal motivations for, and impediments to, help-seeking in a sample of 77
      problem gamblers recruited from agencies and the general community. The results
      indicated that profession help-seeking is predominantly crisis-driven rather than
      being motived by a gradual recognition of problematic behaviour. Shame, denial
      and social factors were identified as the most significant barriers to change
      rather than a lack of knowledge, or dislike of, treatment agencies. The value of
      early interventions including the screening of gamblers in routine medical
      consultations and partner support strategies is discussed.

PMID- 15870985
TI  - Pathological gambling in Montreal's Chinese community: an anthropological
      perspective.
AB  - Pathological gambling has been identified as a major issue in Montreal's Chinese
      community. A variety of sources attest to the fact that, though we live in an
      increasingly heterogeneous society, the services provided to minority communities
      for preventing and treating pathological gambling are inadequate. An
      anthropological approach that takes into account cultural characteristics of
      one's community could lead to better strategies for acknowledgement, definition,
      diagnosis and treatment of pathological gambling among culturally different
      communities. Research paths that could help to provide effective treatment and
      services to specific populations are suggested. An overview of the way the
      Chinese view gambling, pathological gambling and treatment is presented. The
      concepts of fate, destiny and luck in Chinese thought, as well as Montreal's
      Chinese community social norms related to gambling are then described. The
      incorporation of those cultural understandings in future studies and treatment
      attempts is suggested.

PMID- 15870987
TI  - Problem and probable pathological gambling among older adults assessed by the
      SOGS-R.
AB  - This study had three main objectives: to examine the prevalence of gambling and
      problem gambling among older adults, to examine the socio-demographic and
      gambling patterns of people with various South Oaks Gambling Screen Revised (SOGS
      R) scores, and to examine endorsement of the SOGS-R items. The data were drawn
      from telephone interviews conducted with a sample of 1000 older adults, 60 years
      and older, throughout the province of Manitoba. Problem gambling was determined
      from scores on the SOGS-R (Lesieur, H., & Blume, S. (1987). American Journal of
      Psychiatry, 144, 1184-1188; Lesieur, H., & Blume, S. (1993). Journal of Gambling
      Studies, 9, 213-219). The results showed gambling to be a fairly common activity
      among older adults, with 74.7% of participants having gambled in the year prior
      to the study. Of the total sample, 1.6% were gambling at problem levels, and a
      further 1.2% were gambling at probable pathological levels in the past year.
      Inspection of gambling patterns by SOGS-R score failed to reveal a clear and
      consistent distinction between problem gambling and probable pathological
      gambling. Finally, examination of item distribution revealed consistent trends of
      both over and under endorsement of certain items. These results suggest the need
      for either refinement of the SOGS-R for use with older adults, or the development
      of a new measure specific to older adults.

PMID- 15870986
TI  - Genetic studies of pathological gambling: a review of methodology and analyses of
      data from the Vietnam Era Twin Registry.
AB  - Twin studies represent an important and powerful approach to estimating the
      relative contributions of environmental and genetic factors to the expression of
      psychiatric illnesses. In this article, we first explain the rationale for using
      large populations of monozygotic and dizygotic twin pairs to estimate genetic and
      environmental contributions to a disorder and the statistical modeling associated
      with this approach. We then review results from studies of the Vietnam Era Twin
      Registry that use this methodology to examine the etiology of pathological
      gambling (PG) behaviors. The results provide strong evidence for genetic
      contributions to the development of PG in men and set the foundation for future
      studies aimed at identifying the manner in which specific genes and environmental
      factors individually and in conjunction contribute to PG.

PMID- 15870988
TI  - [The Austrian specialist examination for anaesthesiology and intensive care
      medicine. Basic structure and experiences].
AB  - In parallel with Austria's entry into the European Union, the examination system
      for both general practitioners and specialists at the end of their training was
      changed from voluntary to mandatory. Subsequent changes in laws and directives in
      Austria constituted the basis for the development of specific examination
      guidelines for each medical sub-specialty. For "Anaesthesiology and Intensive
      Care Medicine" the decision was made for a structured oral examination after
      successful completion of the part 1 examination of the European Diploma of
      Anaesthesiology. Because of transitional regulations the actual number of
      candidates for the oral examination currently lies way below the expected number
      of 80-100. The decision to demand positive performance in the part 1 examination
      for the European Diploma of Anaesthesiology has, however, already proven that
      this type of combined examination system is of a high standard and will produce
      properly qualified specialists in anaesthesiology.

PMID- 15870989
TI  - [Anesthesia in the univentricular heart. Between scylla and charybdis].

PMID- 15870990
TI  - [Effects of reduced shear stress on inflammatory reactions in vitro. Effects of
      pathological flow conditions on leukocyte-endothelial interactions and monocyte
      tissue factor expression in human cell cultures].
AB  - BACKGROUND: During malperfusion and inflammation leukocyte adhesion is common.
      The purpose of this study was to examine the effects of reduced shear stress on
      leukocyte-endothelial interactions and subsequent inflammatory reactions such as
      up-regulation of tissue factor. METHODS: Isolated neutrophils and monocytes were
      co-incubated with human umbilical venous endothelium at 0-3 dynes/cm(2) in a flow
      chamber. Adhesion and tissue factor expression on adherent leukocytes were
      examined at various flow conditions. RESULTS: At 2-3 dynes/cm(2) adhesion
      occurred only on TNFalpha-activated endothelium. Below 1 dyne/cm(2) similarly
      increased adhesion was also observed on non-activated endothelium. As was
      observed for leukocyte adhesion, these shear stress-dependent cell interactions
      also resulted in an up-regulation of tissue factor on adherent monocytes from non
      activated co-cultures. CONCLUSION: Apart from additional activators of
      inflammation, reduced shear forces may directly contribute to inflammation.

PMID- 15870991
TI  - [Stability of phoneme discrimination in preschool children].
AB  - BACKGROUND: Several tests have been developed to probe phoneme discrimination.
      However, little is known about the stability of discrimination abilities in
      preschool children. We investigated the test-retest reliability of a newly
      developed test material. METHODS: In a prospective study, 30 preschool children
      (5.1-6.3 years old) were tested with a time lag between test 1 and test 2 of 1
      month. Correlational analysis was carried out using 60 minimal pairs consisting
      of real words and nonsense syllables. The choice of items took into consideration
      their frequency in the basic vocabulary as well as phoneme properties such as
      contrast and position. RESULTS: High Cronbach's alpha were found for all
      subscales. For the whole item list, Cronbach's alpha was 0.994. No significant
      gender specific differences were found. DISCUSSION: These data indicate a high
      stability of phoneme discrimination abilities in preschool children. Based on
      these results, the test material can be reliably used to evaluate therapeutic
      strategies to improve discrimination ability.

PMID- 15870992
TI  - [Prosthetic voice rehabilitation after laryngectomy. Failures and complications
      after previous radiation therapy].
AB  - BACKGROUND: Indwelling voice prostheses are state of the art for post
      laryngectomy voice rehabilitation. The aim of this study was to identify the
      impact of radiation prior to tracheoesophageal puncture on success rate and
      complications. PATIENTS AND METHODS: We undertook a retrospective study of 145
      patients who had undergone prosthetic voice restoration between 1990 and 2002
      (Provox) and Provox2). Risks of functional failure and complications in 17
      patients with previous radiation therapy were compared to those of 128 patients
      without such therapy. RESULTS: Previous radiation increased not only the risk of
      functional failure by 2.9 (P=0.023), but also the risk of shunt-related
      complications such as aspiration around the prosthesis (1.51; P=0.046), widening
      of the shunt (2.32; P=0.014), esophageal (2.51; P=0.013) or tracheal (3.29;
      P=0.0023) dislocation of the prosthesis and spontaneous (2.51; P=0.047) or
      surgical closure (3.76; P=0.037) of the shunt. CONCLUSION: Primary
      tracheoesophageal puncture during laryngectomy is recommended in cases without
      previous radiation therapy, especially when post-laryngectomy radiation is
      likely. In patients with previous radiation therapy, generally good success rates
      decrease, however, without absolute contraindication of tracheoesophageal
      puncture. These results may affect salvage surgery concepts.

PMID- 15870993
TI  - [Angiogenic factors in external auditory canal cholesteatoma-fibroblast cell
      culture].
AB  - BACKGROUND: The external auditory canal cholesteatoma (EACC) is characterized by
      hyperproliferation of the epithelial and subepithelial tissue. Compared to normal
      meatal skin, strong expression of FGF-2 and VEGF had previously been detected.
      Many authors reported that FGF-2 acts via VEGF and is induced by hypoxia. Hypoxia
      seems to be pivotal for establishing EACC. Therefore, human EACC fibroblasts were
      investigated by incubating with FGF-2 and determining VEGF. PATIENTS AND METHODS:
      We harvested fibroblasts from human EACC and normal meatal skin and incubated the
      fibroblast culture with 50 ng/ml FGF-2 and determined VEGF concentrations after 1
      4 days. RESULTS: Compared to untreated fibroblast cultures, there was a
      significant increase of VEGF concentration (p<0.05). However, there was no
      significant difference between the proliferation quantities. CONCLUSION: VEGF and
      FGF-2 are possibly involved in a cascade of growth factor activities, which
      modulates their concentration in human-derived EACC fibroblast culture. Exogenous
      FGF-2 increased fibroblast expression for VEGF, which is a major autocrine
      mediator of FGF-2-induced angiogenesis and proliferation.

PMID- 15870994
TI  - [Abscettic pneumonia in a renal transplantation female patient].
AB  - A 39-year old female patient who was kidney transplanted three years ago was
      admitted to hospital with fever of unknown origin for several days. Blood samples
      revealed decreased renal function and increased inflammation parameters. Chest X
      ray and CT scan showed multiple cavernous structures, some with liquid.
      Staphylococcus aureus was detected in blood culture samples. With the aid of
      these results Staphylococcus pneumonia with multiple abscesses was diagnosed. The
      treatment consisted of removal of the infectious focus and a systemic antibiotic
      therapy corresponding to the microbiologic results. We describe a case of
      Staphylococcus pneumonia caused by a infected vascular prosthesis under
      consideration of immunosuppression in a renal transplanted patient.

PMID- 15870996
TI  - [Therapeutic relevance of magnetic resonance imaging in joint injuries in
      children].
AB  - AIM: In this retrospective study, we assessed whether the use of MRI in children
      provides additional, therapeutically relevant information to assist in the
      diagnosis of joint injuries. In addition, we determined whether the usefulness of
      this approach is dependant on age of the child and localisation of the trauma.
      METHOD: MRI of 45 children aged between 3 and 16 years were analysed
      independently by four different investigators (two radiologists, two trauma
      surgeons) and assessed for their therapeutic relevance. RESULT: MRI of the knee
      (n=18) gave additional information in 11 patients (61%) and led to a change in
      the recommended therapy involving arthroscopy in seven patients (39%). MRI of the
      ankle (n=21) provided additional information in 12 patients (57%) and the
      decision for further therapy was influenced in six patients (29%), however, the
      indication for surgery was not influenced. The diagnosis of injuries of the elbow
      (n=6) was changed in four patients (67%), but the therapeutic decision was not
      influenced. CONCLUSION: MRI additional to conventional x-ray provides relevant
      information on the therapeutic procedure to be used for the knee, whereas for the
      ankle and the elbow MRI it rarely delivers additional information relevant to
      therapeutic decision making.

PMID- 15870997
TI  - [The development and biomechanical testing of a femoral press fit fixation for
      hamstring tendons].
AB  - PURPOSE: The purpose of this study was to investigate press fit femoral fixation
      of hamstring tendons and to compare the mechanical properties with press fit
      patellar tendon bone (PTB) fixation. METHODS: The PTB and hamstring tendons of 30
      human cadavers (age: 55.8+/-18.0 years) were used as grafts. An outside-in press
      fit fixation with a knot in the semitendinosus and gracilis graft (SG-K) and an
      inside-out (SG-BI) and an outside-in fixation (SG-BO) with the tendons looped
      over a bone block were compared with a bone-patellar tendon (PT) press fit
      fixation in 30 bovine femora. The angle between the direction of force and bone
      tunnel was 60 degrees. The constructs underwent 20 cycles of loading between 60
      and 260 N. Constructs were loaded until failure at a speed of 1 mm/sec. Graft
      fixation was analyzed in terms of maximum load to failure, stiffness and
      elongation during cyclic stretching. A video analysis of length changes was
      investigated. RESULTS: There was a significant difference in the maximum load to
      failure. The SG-BI fixation was inferior to the other three techniques (Mann
      WhitneyU-test, P<0.01). There was no difference in stiffness between the
      techniques. Length changes of PT-fixation from the first to the fifth loading
      cycle were significantly smaller compared with all other groups (0.73+/-0.58 mm).
      There was no significant difference between the groups from the 15th to the 20th
      cycle of cyclic loading. CONCLUSIONS: Press fit fixation of hamstring grafts is
      technically challenging. However, pull-out forces for SG-O and SG-K were
      equivalent to BPT-graft fixation. Adequate preconditioning for all hamstring
      tendon press fit techniques is crucial.

PMID- 15870998
TI  - [Treatment of chronic knee dislocation with an external fixator].
AB  - Chronic knee dislocations are rare but represent a therapeutic challenge. A
      staged concept is necessary to correctly address the pathological components.
      This article uses a case study to provide an algorithm for the successful
      treatment of chronic knee dislocations.

PMID- 15870999
TI  - Influence of interspecific competition on the recruitment behavior and liquid
      food transport in the tramp ant species Pheidole megacephala.
AB  - This study was conducted on the reactions of Pheidole megacephala scouts when
      finding liquid food sources situated on territories marked by competing dominant
      ant species or on unmarked, control areas to see if the number of recruited
      nestmates is affected and if soldiers behave in ways adapted to the situation. We
      show that scouts recruit more nestmates, particularly soldiers, on marked rather
      than on unmarked areas. This recruitment allows P. megacephala to organize the
      defence and rapid depletion of these food sources prior to any contact with
      competitors. Soldiers can carry liquid foods both (1) in their crops like other
      Myrmicinae and (2), in a new finding concerning myrmicine ants, under their heads
      and thoraxes like certain poneromorph genera because the droplets adhere through
      surface tension strengths. Later, the liquids stored in the crop are distributed
      to nestmates through regurgitations during trophallaxis and the external droplets
      are distributed through "social buckets", or the mode of liquid food transfer
      common in poneromorphs. Their flexibility to use or not use the latter technique,
      based on the situation, corroborates other reports that Pheidole soldiers have a
      relatively large behavioral repertoire.

PMID- 15871000
TI  - Acoustic mirror effect increases prey detection distance in trawling bats.
AB  - Many different and phylogenetically distant species of bats forage for insects
      above water bodies and take insects from and close to the surface; the so-called
      'trawling behaviour'. Detection of surface-based prey by echolocation is
      facilitated by acoustically smooth backgrounds such as water surfaces that
      reflect sound impinging at an acute angle away from the bat and thereby render a
      prey object acoustically conspicuous. Previous measurements had shown that the
      echo amplitude of a target on a smooth surface is higher than that of the same
      target in mid-air, due to an acoustic mirror effect. In behavioural experiments
      with three pond bats (Myotis dasycneme), we tested the hypothesis that the
      maximum distances at which bats can detect prey are larger for prey on smooth
      surfaces than for the same prey in an airborne situation. We determined the
      moment of prey detection from a change in echolocation behaviour and measured the
      detection distance in 3D space from IR-video recordings using stereo
      photogrammetry. The bats showed the predicted increase in detection distance for
      prey on smooth surfaces. The acoustic mirror effect therefore increases search
      efficiency and contributes to the acoustic advantages encountered by echolocating
      bats when foraging at low heights above smooth water surfaces. These acoustic
      advantages may have favoured the repeated evolution of trawling behaviour.

PMID- 15871001
TI  - Larval competition in weevils Revena rubiginosa (Coleoptera: Curculionidae)
      preying on seeds of the palm Syagrus romanzoffiana (Arecaceae).
AB  - Inter- and intraspecific local resource competition may lead to the selection of
      specific adaptive individual characteristics to overcome interference
      competition. A highly selective scenario is predictable for interference
      competition among seed preying weevil larvae that live in and feed upon a single
      host seed. This scenario is found in Syagrus romanzoffiana palm seeds which are
      predated by Revena rubiginosa (Curculionidae) larvae. Although multiple
      infestation of one seed by weevil larvae can occur, invariably only one
      individual survives and develops in each host seed. A strong competition between
      the first instar larvae in a restricted window of host fruit development stages
      leads to physical interactions of conspecifics by ovicide or direct fighting
      using falcate mandibles. The occurrence of this type of mandible is synchronized
      with fruit development and restricted to instars with probable competition, as
      infestation occurs only while the endocarp is soft. Only after lignification of
      the endocarp the larva changes into the next instar. Mandibles of subsequent
      instars differ markedly from those of the first instar. The new mandibles can
      scrape the solid endosperm but are unable to perforate and kill conspecifics.
      These findings give strong evidence for the selective pressure of intraspecific
      competition, where special behaviour, mandible morphology and synchronization of
      its changes with the seed development contribute to individual benefit that
      involves the killing of conspecifics, since one host seed can only maintain a
      single larva throughout its complete development.

PMID- 15871003
TI  - [Thrombolysis of the basilar artery: 5-year results from the Saarland stroke
      registry].
AB  - Acute thrombosis of the basilar artery has a fatal outcome if left untreated. The
      relatively good prognosis with intra-arterial thrombolysis makes it the therapy
      of choice for acute basilar thrombosis. In the Saarland stroke registry, we
      analyzed 47 patients with angiographically proven basilar artery thrombosis
      within the last 5 years. We observed a better outcome in patients with good
      income, with recanalization, and a short time between onset of symptoms and start
      of thrombolysis. The complications, such as intracerebral bleedings, occurred
      only in the group treated with rt-PA. Intra-arterial thrombolysis with urokinase
      or rt-PA is a relatively safe therapy, but should be performed in
      neuroradiological centers. With progressing symptoms the therapeutic window can
      be stretched up to 12 h, but coma lasting for more than 4 h is related to a bad
      outcome.

PMID- 15871002
TI  - [Sinus and venous thrombosis--differential diagnosis of acute stroke].
AB  - Thrombosis of the cerebral veins and sinus is a rare, but important cause of
      stroke. The clinical picture varies. This contribution addresses the etiology,
      clinical picture, imaging procedures, and therapeutic options.

PMID- 15871004
TI  - [Lymph node dissection in patients with renal cell carcinoma].
AB  - The role of lymph node dissection in renal cell carcinoma has been controversial
      for decades. However, the results of the only prospective randomised study
      concerning this issue (EORTC 30881) are preliminary. Retrospective analyses were
      not able to demonstrate a diagnostic or therapeutic benefit of an extended lymph
      node dissection. Suspicious lymph nodes (imaging, palpation) should be excised
      during nephrectomy.

PMID- 15871005
TI  - [The role of pelvic lymphadenectomy in clinically localised prostate cancer].
AB  - Lymph node dissection remains the only reliable method for exact staging to date.
      Extended lymphadenectomy including tissue along the external iliac vein, the
      obturator fossa, and along the internal iliac vessels should be performed in all
      patients undergoing radical prostatectomy. There is an increasing amount of data
      suggesting that removal of all diseased nodes, which contain minimal metastatic
      disease, may have a positive impact on disease-free and, perhaps, on overall
      survival. Due to the relatively benign course of the disease, longer follow-up
      periods are still necessary to make a definitive statement.

PMID- 15871006
TI  - [Lymphadenectomy for bladder cancer. Diagnostic and prognostic significance as
      well as therapeutic benefit].
AB  - BACKGROUND: Pelvic lymphadenectomy for invasive bladder cancer is not a
      standardized procedure and its relevance for staging and prognoses is still under
      discussion. A number of retrospective studies have demonstrated a positive
      correlation between extent of lymphadenectomy and prognosis after radical
      cystectomy. MATERIALS AND METHODS: In a retrospective study, we correlated the
      extent of lymphadenectomy with survival after radical cystectomy. Thereafter, we
      conducted a prospective study to investigate the limits of pelvic lymphadenectomy
      and the pattern of lymphatic spread. RESULTS: Retrospectively, we found a
      significantly better survival for patients when 15 and more lymph nodes were
      removed. The individual surgeon was also evaluated as an important prognostic
      factor. CONCLUSIONS: Based on retrospective data, an extended and complete pelvic
      lymphadenectomy improves the prognosis. The cranial border should be at least at
      the level of the aortic bifurcation. A prospective randomized study will have to
      clarify the effect of lymphadenectomy on the prognosis of patients after radical
      cystectomy.

PMID- 15871007
TI  - [Principle problems of lymph node surgery].

PMID- 15871008
TI  - Pendra goes Dutch: lessons for the CE mark in Europe.
AB  - The development of a truly non-invasive continuous glucose sensor is an elusive
      goal. We describe the rise and fall of the Pendra device. In 2000 the company
      Pendragon Medical introduced a truly non-invasive continuous glucose-monitoring
      device. This system was supposed to work through so-called impedance
      spectroscopy. Pendra was Conformite Europeenne (CE) approved in May 2003. For a
      short time the Pendra was available on the Dutch direct-to-consumer market. A
      post-marketing reliability study was performed in six type 1 diabetes patients.
      Mean absolute difference between Pendra glucose values and values obtained
      through self-monitoring of blood glucose was 52%; the Pearson's correlation
      coefficient was 35.1%; and a Clarke error grid showed 4.3% of the Pendra readings
      in the potentially dangerous zone E. We argue that the CE certification process
      for continuous glucose sensors should be made more transparent, and that a
      consensus on specific requirements for continuous glucose sensors is needed to
      prevent patient exposure to potentially dangerous situations.

PMID- 15871009
TI  - Usefulness of pulse pressure for the detection of extent and severity of coronary
      artery disease in type 2 diabetic patients with silent myocardial ischaemia at
      exercise stress test.

PMID- 15871010
TI  - [Cementless stems of the hip. Current status].
AB  - Optimal fixation of cementless stems is a precondition for long-lasting
      stability. Thus, anchorage, stabilizers, material and surface are of essential
      importance. To achieve primary stability, good rotational, tilting and axial
      stability is necessary. Stabilizers such as fins and ribs optimize stability. The
      CCD-angle and length of neck-axis determine the offset (laterality), leg-length
      and center of rotation. The stem, is responsible for the fixation of the
      prosthesis and for transmitting forces to the bone. The types of fixation are
      epiphyseal (the femoral head is covered by a cup prosthesis), metaphyseal and
      meta-diaphyseal (with straight or anatomically shaped monoblock-prostheses of
      different lengths, modular and custom-made prostheses) and diaphyseal (using
      predominantly modular systems). Titanium alloys are the predominate material for
      cementless stems. The surfaces are generally corundum-blasted or plasma sprayed.
      For metaphyseal and meta-diaphyseal stems, survival rates from 95 to 98% have
      been reached after 15 years. Diaphyseal-fixed stems have mid-term survival-rates
      of 92-99%.

PMID- 15871011
TI  - Noninvasive pressure support ventilation vs. continuous positive airway pressure
      in acute hypercapnic pulmonary edema.
AB  - OBJECTIVE: This study compared noninvasive pressure support ventilation (NIPSV)
      and continuous positive airway pressure (CPAP) in patients with acute hypercapnic
      pulmonary edema with regard to resolution time. DESIGN AND SETTING: Randomized
      prospective study in an emergency department. PATIENTS AND PARTICIPANTS: We
      randomly assigned 36 patients with respiratory failure due to acute pulmonary
      edema and arterial hypercapnia (PaCO(2) >45 mmHg) to NIPSV (n=18) or CPAP through
      a face mask (n=18). MEASUREMENTS AND RESULTS: Electrocardiographic and
      physiological measurements were made over 36 h. There was no difference in
      resolution time defined as clinical improvement with a respiratory rate of fewer
      than 30 breaths/min and SpO(2)of 96% or more between CPAP and NIPSV groups.
      Arterial carbon dioxide tension was significantly decreased after 1 h of
      ventilation (CPAP, 60.5+/-13.6 to 42.8+/-4.9 mmHg; NIPSV, 65.7+/-13.6 to 44.0+/
      5.5 mmHg); respective improvements were seen in pH (CPAP, 7.22+/-0.11 to 7.37+/
      0.04; NIPSV, 7.19+/-0.11 to 7.38+/-0.04), SpO(2) (CPAP, 86.9+/-3.7% to 95.1+/
      2.6%; NIPSV, 83.7+/-6.6% to 96.0+/-2.9%), and respiratory rate (CPAP, 37.9+/-4.5
      to 21.3+/-5.1 breaths/min; NIPSV, 39.8+/-4.4 to 21.2+/-4.6 breaths/min). No
      significant differences were seen with regards to endotracheal intubation and in
      hospital mortality. CONCLUSIONS: NIPSV proved as effective as CPAP in the
      treatment of patients with acute pulmonary edema and hypercapnia but did not
      improve resolution time.

PMID- 15871012
TI  - The effects of menstrual cycle on the knee joint position sense: preliminary
      study.
AB  - The purpose of this study was to determine the effects of menstrual cycle on
      proprioception by using the active knee joint position sense test (JPST). The 19
      healthy women (ages between 20 years and 27 years) who have normal regular
      menstrual cycle were included in the study. We applied JPSTs at two different
      directions throughout the three different phases of the menstrual cycle, i.e.
      menstrual, follicular, and early luteal in dominant knees. When we started from
      flexion (90 degrees ), target angles were 70 degrees , 50 degrees , and 30
      degrees and we started from extension (0 degrees ), target angles were 20 degrees
      , 40 degrees and 60 degrees . The absolute reposition errors from the target
      angles have been evaluated. Results have shown that reposition errors from the
      target angle at 40 degrees , 50 degrees and 70 degrees of knee angles were higher
      in the menstrual phase than that of the follicular phase (P<0.05). In addition,
      higher value of reposition error from the target angle at 40 degrees was found in
      the menstrual phase compared to luteal phase (P<0.05). In conclusion, we have
      demonstrated that active JPST was significantly reduced in the menstruation
      period.

PMID- 15871013
TI  - The TRPC2 ion channel and pheromone sensing in the accessory olfactory system.
AB  - The mammalian vomeronasal organ (VNO) has emerged as an excellent model to
      investigate the signaling mechanisms, mode of activation, biological function,
      and molecular evolution of transient receptor potential (TRP) channels in real
      neurons and real physiological systems. TRPC2, a member of the canonical TRPC
      subfamily, is highly localized to the dendritic tip of vomeronasal sensory
      neurons. Targeted deletion of the TRPC2 gene has established that TRPC2 plays a
      fundamental role in the detection of pheromonal signals by the VNO. TRPC2
      deficient mice exhibit striking behavioral defects in the regulation of sexual
      and social behaviors. A novel Ca(2+)-permeable, diacylglycerol-activated cation
      channel found at the dendritic tip of vomeronasal neurons is severely defective
      in TRPC2 mutants, providing the first clear example of native diacylglycerol
      gated cation channels in the mammalian nervous system. The TRPC2 gene has become
      an important marker for the evolution of VNO-dependent pheromone signaling in
      primates.

PMID- 15871014
TI  - Prophylactic and therapeutic properties of a sodium citrate preparation in the
      management of calcium oxalate urolithiasis: randomized, placebo-controlled trial.
AB  - The purpose of this study was to investigate the prophylactic and therapeutic
      effects of a hitherto untested preparation containing sodium citrate in the
      management of calcium oxalate urolithiasis. In this study, a host of calcium
      oxalate kidney stone risk factors was investigated using a randomised, placebo
      controlled, "within-patient" clinical trial. The trial involved four groups of
      subjects: healthy male controls, healthy female controls , calcium oxalate stone
      forming males and calcium oxalate stone-forming females. There were 30 subjects
      in each group. Twenty subjects in each group ingested the preparation containing
      sodium citrate and ten subjects in each group ingested a placebo for 7 days.
      Collection of 24 h urines were carried out at baseline, at day 7 and day 10 (i.e.
      3 days after suspension of drug/placebo ingestion). These were analysed for
      biochemical and physicochemical risk factors. They were also tested for their
      inhibitory properties in crystallization experiments. Data were statistically
      analyzed using analysis of variance (ANOVA). Key risk factors were significantly
      and beneficially altered across all groups after ingestion of the preparation.
      The pH and urinary citrate excretion increased while urinary oxalate and calcium
      excretions decreased, as did relative supersaturations of calcium oxalate and
      uric acid. In addition, inhibition of calcium oxalate crystallization increased.
      Beneficial carryover effects were observed for some risk factors. The results of
      this study have demonstrated, for the first time, that a sodium citrate
      containing preparation favourably alters the risk factors for calcium oxalate
      urolithiasis.

PMID- 15871016
TI  - Radioiodine treatment of non-toxic multinodular goitre: effects of combination
      with lithium.
AB  - PURPOSE: This study aimed to evaluate the effects of radioiodine ((131)I), alone
      or in combination with lithium, on thyroid volume and the prevention of
      radioiodine-induced thyrotoxicosis. This is the first clinical trial including
      only patients with multinodular goitre, normal TSH values and negative anti
      thyroid auto-antibodies at baseline. METHODS: Eighty consecutive patients were
      randomised to receive (131)I plus lithium (group I+L) or (131)I alone (group I).
      Thyroid ultrasonography and biochemical analyses were performed at baseline and
      at 1, 3, 6, 12 and 24 months after treatment. RESULTS: At 1-4 weeks after
      treatment, (131)I-induced hyperthyroidism was observed in 58.8% of patients and
      was prevented by lithium administration. A low incidence of hypothyroidism (19%)
      was recorded at 24 months, whereas up to 44% of patients developed anti-thyroid
      antibodies. A significant reduction in thyroid volume was observed after (131)I,
      with a mean decrease of 47.2% (median 48.2%) at 24 months, without differences
      between the groups. Moreover, it was shown that the decrease in thyroid volume
      after (131)I was also due to the significant shrinkage of thyroid nodules.
      CONCLUSION: This demonstrates that adjunctive lithium is able to reduce
      radioiodine-induced hyperthyroidism. Therefore, such treatment appears to be safe
      in older patients and those with underlying cardiovascular disease. In the
      present large series, (131)I therapy was demonstrated to be highly effective in
      reducing thyroid and nodular volume even in patients treated with low (131)I
      doses (2.5 MBq/ml of thyroid tissue), further supporting the view that
      radioiodine therapy represents a real alternative to surgery.

PMID- 15871015
TI  - A biochemical and structural analysis of genetic diversity within the HLA-A*11
      subtype.
AB  - The HLA-A*11 subtype includes 17 naturally occurring variants (-A*1101 to 
      A*1117) distributed among different ethnic groups worldwide. At present, only HLA
      A*1101 has been characterized at the molecular, structural, and immunological
      level. Developing similar knowledge on other HLA-A*11 alleles is highly important
      for bone marrow and graft transplantation. This is also important to better
      understand disease linkages within the HLA-A*11 subtype given that HLA-A*11
      molecules are associated with resistance to acquisition of HIV-1 infection and
      various autoimmune diseases. To broaden our understanding of HLA-A*11 molecules,
      we have determined the impact of natural polymorphism on the peptide-binding
      properties of several HLA-A*11 molecules: -A*1103, -A*1106, -A*1108, -A*1110, 
      A*1111, and -A*1114. We used an approach that combines data from thermal
      stability studies of recombinant, soluble forms of these molecules in complex
      with HIV-1 peptides, together with a detailed structural analysis of the
      resulting HLA-A*11 molecule/peptide complexes based on crystal and molecular
      model structures. Our analysis shows that natural polymorphism within the HLA
      A*11 subtype is distributed along the alpha1 and alpha2 helices of the peptide
      binding groove, in marked contrast to the pattern of polymorphism in HLA-A*2 and
      HLA-B*27 subtypes. Natural polymorphism greatly altered the abilities of
      individual -A*11 molecules to form stable complexes with HIV-1 peptides. In
      comparison to -A*1101, natural polymorphism altered the peptide-presenting
      properties of -A*1103, -A*1108, and -A*1114 and has the potential to affect the
      peptide-selecting properties of -A*1106, -A*1110, and -A*1111 as well. Overall,
      our findings suggest that HLA-A*11 molecules may stimulate alloreactive CD8+
      cytotoxic T-cell responses.

PMID- 15871017
TI  - Anti-CD20 antibody (Rituximab) therapy in a myasthenia gravis patient with
      follicular lymphoma.

PMID- 15871018
TI  - Mutations of the HFE gene among Turkish hereditary hemochromatosis patients.
AB  - Since the discovery of the HFE gene, C282Y and H63D mutations have been reported
      as significantly correlated with clinically manifested hereditary hemochromatosis
      (HH). As the other genes involved in iron metabolism have been described, non-HFE
      cases of HH have been identified. Since in the general Turkish population, the
      C282Y mutation is not found and the H63D mutation is of high frequency, we aimed
      to determine mutations in the HFE genes in our patients with HH. The HFE gene of
      the five patients with HH were sequenced. C282Y mutation was absent, and all HH
      patients were heterozygote for H63D mutation. No other mutation was found in HFE
      gene by sequencing. Although the higher allele frequency of the H63D mutation in
      Turkish HH patients than in the general population implies a role of the H63D
      mutation in iron overload, there is a strong possibility that Turkish HH patients
      have non-HFE hemochromatosis.

PMID- 15871020
TI  - [Reproducibility of measurements of the peripapillary retinal nerve fibre layer
      thickness. Optical coherence tomography versus retinal thickness analyzer].
AB  - PURPOSE: The aim of this study was to compare the intra- and inter-examiner
      reproducibility of measurements obtained by optical coherence tomography (OCT)
      and retinal thickness analyzer (RTA). PATIENTS AND METHODS: During a period of 2
      months, 22 eyes of 16 patients and 6 healthy subjects were included. Two
      examiners (EMH, RK) successively performed three measurements of the
      peripapillary retinal nerve fibre layer (RNFL) thickness with RTA and OCT. The
      reproducibility of three individual measurements of one examiner (intra-examiner)
      as well as the reproducibility of the measurements between both examiners (inter
      examiner) was evaluated using the Friedman test and sign test. RESULTS: The
      average thickness of the peripapillary RNFL was 154.4 microm for the first
      investigator (EMH) and 155.1 microm for the other investigator (RK) measured with
      RTA. The results obtained by OCT were 137.3 microm (EMH) and 138.9 microm (RK),
      respectively, generally indicating a threefold smaller range. Comparing the three
      measurements of one single examiner, no appreciable intra-observer dependency
      neither for RTA (EMH: p=0.19, RK: p=0.95) nor for OCT (EMH: p=0.51, RK: p=0.62)
      was observed. Inter-examiner analysis for RTA and OCT also revealed an acceptable
      reproducibility. CONCLUSIONS: Measurements of peripapillary RNFL thickness using
      RTA and OCT exhibited intra- and inter-observer agreement.

PMID- 15871019
TI  - Novel interaction of the Hsp90 chaperone machine with Ssl2, an essential DNA
      helicase in Saccharomyces cerevisiae.
AB  - Hsp90 is an essential molecular chaperone that is critical for the activity of
      diverse cellular proteins. Hsp90 functions with a number of co-chaperone
      proteins, including Sti1/Hop. We conducted a genetic screen in Saccharomyces
      cerevisiae to isolate mutations that exhibit enhanced growth defects in the
      absence of STI1. We obtained mutations in genes encoding components of the Hsp90
      chaperone machine, HSC82, CPR7 and YDJ1, and two essential genes, SSL2 and UTP21,
      not previously linked to Hsp90. Ssl2, the yeast homologue of XPB, is an ATP
      dependent DNA helicase that is a component of the TFIIH multiprotein complex and
      has dual functions in transcription and DNA repair. In order to determine whether
      Ssl2 function is dependent on Hsp90, we further examined the interaction between
      Ssl2 and Hsp90. Multiple mutant alleles of SSL2 exhibited a pronounced growth
      defect when co-expressed with a mutant allele of Hsp90. In addition, isolation of
      Ssl2 protein resulted in the co-purification of Hsp90 and Sti1, suggesting that
      Ssl2 and Hsp90 are in the same protein complexes in vivo. These results suggest a
      novel role for Hsp90 in the essential cellular functions of transcription and DNA
      repair.

PMID- 15871021
TI  - [Patients with secondary open-angle glaucoma in pseudoexfoliation (PEX) syndrome
      among a population with high prevalence of PEX. Clinical findings and
      morphological and surgical characteristics].
AB  - BACKGROUND: The second most frequent treatable cause of noninfectious blindness
      in Oman is high-pressure glaucoma. Therefore, in 2002 a study was performed at
      our department of ophthalmology to evaluate pseudoexfoliation (PEX) in glaucoma
      patients. METHODS: In a prospective comparative cohort study, of 204 glaucoma
      eyes, 135 open-angle glaucomas were evaluated by biomicroscopy, papillometry, and
      electron microscopy and followed up after 6 months. RESULTS: The incidence of PEX
      glaucomas relative to all glaucomas was 50.9% and to open-angle glaucomas 77%.
      The IOP level in PEX was higher than in POAG; the CDR, neuroretinal rim zone, and
      the visual field loss were not significantly different. In 38 of 104 operated PEX
      glaucoma eyes, the postoperative visual acuity deteriorated although the IOP was
      controlled. CONCLUSIONS: PEX high-pressure glaucomas account for half of all
      glaucomas in the eastern region of the Arabian peninsula. Surgical outcomes
      feature a high percentage of postoperative reduction of vision in the late PEX
      stage.

PMID- 15871022
TI  - [Association between classic cardiovascular risk factors and age-related
      maculopathy (ARM). Results of the baseline examination of the Munster Aging and
      Retina Study (MARS)].
AB  - BACKGROUND: Epidemiological studies have reported inconsistent associations
      between cardiovascular risk factors and the occurrence of age-related maculopathy
      (ARM). METHODS: In the baseline examination of the Muenster Aging and Retina
      Study (MARS), we assessed this potential relationship in 1060 subjects who
      underwent clinical and ophthalmologic examinations. The ARM status was graded
      according to international standardized classifications. RESULTS: There were 974
      eye pairs available for analysis. Smoking, hypertension, hypercholesterolemia,
      and a history of myocardial infarction or stroke were found significantly more
      often in patients with ARM. There were no statistically significant multivariate
      associations between overweight, diabetes, or a history of myocardial infarction
      or stroke. CONCLUSIONS: Our results confirm previous epidemiological studies
      pointing to a potential role of atherosclerotic processes in the development of
      ARM.

PMID- 15871023
TI  - [Correlation between glaucomatous hemifield scotomas and measurements of nerve
      fiber layer thickness using scanning laser polarimetry].
AB  - BACKGROUND: The purpose of the present study was to investigate wether a
      reduction of the retinal nerve fiber layer (RNFL) in patients with hemifield
      scotoma can be measured with scanning laser polarimetry and wether regional RNFL
      parameters can be correlated with the corresponding visual field indices.
      PATIENTS AND METHODS: We included one eye from each of 40 normal subjects and one
      eye from each of 40 glaucoma patients. Automated perimetry was performed and the
      RNFL was analyzed. RESULTS: HMD values obtained by white-white (W/W) and blue
      yellow (B/Y) perimetry failed to correlate significantly with most of the
      corresponding RNFL parameters obtained with the GDx. Significant correlations
      were only shown for the inferior HMD (W/W and B/Y) and the superior ratio,
      superior average, and deviation superior. Furthermore, we found a high
      correlation between differences of upper and lower GDx parameters and differences
      of upper and lower visual field indices of W/W and B/Y perimetry. CONCLUSIONS:
      Scanning laser polarimetry can detect differences in RNFL sectors in patients
      with functional hemifield differences and carries the potential to detect changes
      in RNFL thickness at an early stage.

PMID- 15871024
TI  - [Stem cell-based therapies for retinal disorders].
AB  - In the context of cell-based therapies for hereditary retinal dystrophies and
      other retinal disorders, interest has focussed on the therapeutic potential of
      embryonic and tissue-specific stem cells. Stem cells are characterised by their
      capacity for self-renewal and by their multipotentiality. Because of these
      properties, they can be expanded in vitro and eventually differentiated into
      "desired" specialized cell types. Stem cells are not only candidate cells for the
      development of cell replacement strategies, but are also interesting cells for
      the establishment of ex vivo gene therapies. Here, we discuss recent experimental
      work performed to evaluate the therapeutic potential of embryonic, mesenchymal,
      hematopoietic, neural and retinal stem cells for the treatment of inherited
      retinal dystrophies and other retinal diseases.

PMID- 15871025
TI  - [Analysis of optical parameters after cataract surgery and implantation of
      foldable lens].
AB  - PURPOSE: Within the first few weeks after cataract surgery, changes of refraction
      can occur in patients with "clear cornea" surgery and implantation of foldable
      lenses. The possible reasons were analyzed. METHOD: In 71 consecutive patients we
      determined axial length, anterior chamber depth, corneal refraction, and corneal
      thickness prior to cataract surgery, on the 1st postoperative day, and at a
      follow-up control after obtaining stable refraction. We divided the patients into
      three groups: patients with no change of refraction between the 1st postoperative
      day and the follow-up (group A), patients with hyperopic shift of refraction
      (group B), and patients with myopic shift of refraction (group C). RESULTS: In
      all three groups we measured no significant postoperative change of the axial
      length. Central corneal thickness increased by approximately 37 microm on the 1st
      postoperative day and had normalized at the time of control. Anterior chamber
      depth decreased in all groups by approximately 0.44 mm between the 1st
      postoperative day and the follow-up. Central corneal refraction showed an
      decrease in groups B and C and an increase in group A. The standard deviation was
      very high in all groups. CONCLUSIONS: The postoperative change of refraction
      depends on multiple factors among which changes of the anterior chamber depths,
      the corneal refraction, the swelling of the cornea, and the axial length can play
      a role.

PMID- 15871026
TI  - Simultaneous and successive colour discrimination in the honeybee (Apis
      mellifera).
AB  - The colour discrimination of individual free-flying honeybees (Apis mellifera)
      was tested with simultaneous and successive viewing conditions for a variety of
      broadband reflectance stimuli. For simultaneous viewing bees used form vision to
      discriminate patterned target stimuli from homogeneous coloured distractor
      stimuli, and for successive discrimination bees were required to discriminate
      between homogeneously coloured stimuli. Bees were significantly better at a
      simultaneous discrimination task, and we suggest this is explained by the
      inefficiency with which the bees' brain can code and retrieve colour information
      from memory when viewing stimuli successively. Using simultaneous viewing
      conditions bees discriminated between the test stimuli at a level equivalent to 1
      just-noticeable-difference for human colour vision. Discrimination of colours by
      bees with simultaneous viewing conditions exceeded previous estimates of what is
      possible considering models of photoreceptor noise measured in bees, which
      suggests spatial and/or temporal summation of colour signals for fine
      discrimination tasks. The results show that when behavioural experiments are used
      to collect data about the mechanisms facilitating colour discrimination in
      animals, it is important to consider the effects of the stimulus viewing
      conditions on results.

PMID- 15871027
TI  - Intracranial pressure monitoring in children with single suture and complex
      craniosynostosis: a review.
AB  - INTRODUCTION: One third of patients with craniofacial dysostosis syndromes and
      about 15-20% of children with single suture craniostenosis have a documented
      increase in intracranial pressure (ICP). The early detection of intracranial
      hypertension is important in order to reduce the risks for brain development and
      visual function. However, in children with craniosynostosis, the clinical
      manifestations of abnormally increased ICP are difficult to detect, as the
      majority of patients may have neither warning signs nor symptoms for a long
      period of time. REVIEW: Moreover, data from the literature suggest that neither
      fundoscopic nor radiological findings are necessarily related to intracranial
      pressure recordings in this type of pathology. In this context prolonged ICP
      monitoring seems actually to be the most valuable diagnostic tool. Extradural,
      subdural, and intraparenchymal devices have been used, and different softwares
      have been employed for PC storage and analysis of the data obtained. Most recent
      series consider mean ICP combined with plateaux waves as the most sensitive
      indicators in the final evaluation of the results. CONCLUSIONS: The analysis of
      the literature demonstrates a significant difference in the prevalence of raised
      ICP preoperatively between non-syndromic and syndromic patients. Among the non
      syndromic children, a direct relation between the number of sutures involved and
      raised ICP is documented. The analysis of plateaux waves seems to be particularly
      important in children with borderline mean ICP values. Persistent postoperative
      raised ICP has been described in 6-15% of patients with craniofacial dysostosis.
      It must be related to the multifactorial etiology of increased ICP in these
      patients, which includes cerebral venous congestion, upper airway obstruction,
      and hydrocephalus.

PMID- 15871028
TI  - Nitric oxide synthase inhibition results in immediate postoperative recovery of
      gastric, small intestinal and colonic motility in awake rats.
AB  - BACKGROUND: Nitric oxide (NO) is known to inhibit gastrointestinal motility.
      However, no detailed analysis of gastric, small intestinal and colonic motor
      effects, including effects on contraction frequency, has, as yet, been reported
      after NO inhibition in awake rats. We therefore investigated the effects of NO
      synthase inhibition on gastric, small intestinal and colonic motility in awake
      rats under baseline conditions and in a postoperative ileus model. METHODS: In
      Sprague-Dawley rats, strain gauge transducers were sutured either to the gastric
      corpus, the small intestine or the colon. After 3 days, L-NMMA (NO synthase
      inhibitor), D-NMMA or vehicle was given i.v., while the motility was recorded
      continuously. In addition, postoperative gastric, small intestinal or colonic
      motility was investigated after L-NMMA or vehicle treatment prior to abdominal
      surgery. The motility index, the contraction amplitude, the area under the
      contraction amplitude and the contraction frequency were analysed. RESULTS: L
      NMMA decreased gastric motility to 60+/-8% for about 15 min, but continuously
      increased small intestinal motility to 221+/-22% and colonic motility to 125+/-7%
      compared to baseline (baseline=100%; p<0.01 for all comparisons). L-NMMA
      increased the contraction frequency throughout the gastrointestinal tract
      (stomach, 13+/-2%; small intestine, 8+/-1%; colon, 16+/-5%; p<0.01 vs. baseline
      for all comparisons). L-NMMA injection prior to surgery did not prohibit
      intraoperative inhibition of gastrointestinal motility, but did result in
      immediate recovery of gastric, small intestinal and colonic motility
      postoperatively (L-NMMA vs. vehicle, 0-60 min postoperatively; stomach, 90+/-9%
      vs. 53+/-3%; small intestine, 101+/-5% vs. 57+/-3%; colon, 134+/-6% vs. 60+/-5%;
      p<0.01 for all comparisons; no significant difference between preoperative
      baseline motility and L-NMMA treated rats postoperatively). CONCLUSIONS: Under
      baseline conditions, endogenous NO inhibits small intestinal and colonic motility
      and gastric, small intestinal and colonic contraction frequency in awake rats. In
      the early postoperative period, endogenous NO is a major inhibitory component
      that seems to constitute the common final pathway of mediators and the neural
      pathways inhibiting gastrointestinal motility in rats.

PMID- 15871029
TI  - Expressing TERF1 in tobacco enhances drought tolerance and abscisic acid
      sensitivity during seedling development.
AB  - Previously, we reported on a tomato ERF transcription activator, TERF1, which was
      concluded to act as a linker between ethylene and osmotic signal pathways. We now
      report on the regulatory role of TERF1 in ABA sensitivity and drought response
      during seedling development. Northern blotting analysis indicated that the
      transcripts of TERF1 were significantly accumulated in response to drought, cold
      and ABA. TERF1 activated GCC box- or DRE-driven reporter gene expression in
      transient expression assay, subsequently increasing the tolerance to drought and
      the osmoticum, PEG6000, in tobacco expressing TERF1. Further tests showed that
      TERF1 did not affect the seed germination, but greatly enhanced the sensitivity
      during tobacco seedling development under ABA treatment. This ABA
      hypersensitivity in transgenic TERF1 tobacco is both indirect ethylene action and
      expressions of ABA responsive genes, demonstrating that TERF1 is a
      multifunctional ERF protein that can integrate different stress signal pathways.

PMID- 15871031
TI  - The formation, vacuolar localization, and tonoplast transport of salicylic acid
      glucose conjugates in tobacco cell suspension cultures.
AB  - The metabolism of salicylic acid (SA) in tobacco (Nicotiana tabacum L. cv. KY 14)
      cell suspension cultures was examined by adding [7-14C]SA to the cell cultures
      for 24 h and identifying the metabolites through high performance liquid
      chromatography analysis. The three major metabolites of SA were SA 2-O-beta-D: 
      glucose (SAG), methylsalicylate 2-O-beta-D: -glucose (MeSAG) and
      methylsalicylate. Studies on the intracellular localization of the metabolites
      revealed that all of the SAG associated with tobacco protoplasts was localized in
      the vacuole. However, the majority of the MeSAG was located outside the vacuole.
      The tobacco cells contained an SA inducible SA glucosyltransferase (SAGT) enzyme
      that formed SAG. The SAGT enzyme was not associated with the vacuole and appeared
      to be a cytoplasmic enzyme. The vacuolar transport of SAG was characterized by
      measuring the uptake of [14C]SAG into tonoplast vesicles isolated from tobacco
      cell cultures. SAG uptake was stimulated eightfold by the addition of MgATP. The
      ATP-dependent uptake of SAG was inhibited by bafilomycin A1 (a specific inhibitor
      of the vacuolar H(+)-ATPase) and dissipation of the transtonoplast H(+)
      electrochemical gradient. Vanadate was not an inhibitor of SAG uptake. Several
      beta-glucose conjugates were strong inhibitors of SAG uptake, whereas glutathione
      and glucuronide conjugates were only marginally inhibitory. The SAG uptake
      exhibited Michaelis-Menten type saturation kinetics with a K(m) and V(max) value
      of 11 microM and 205 pmol min-1 mg-1, respectively, for SAG. Based on the
      transport characteristics it appears as if the vacuolar uptake of SAG in tobacco
      cells occurs through an H(+)-antiport-type mechanism.

PMID- 15871030
TI  - Molecular and cell biology of arbuscular mycorrhizal symbiosis.
AB  - The roots of most extant plants are able to become engaged in an interaction with
      a small group of fungi of the fungal order Glomales (Glomeromycota). This
      interaction-arbuscular mycorrhizal (AM) symbiosis-is the evolutionary precursor
      of most other mutualistic root-microbe associations. The molecular analysis of
      this interaction can elucidate basic principles regarding such associations. This
      review summarizes our present knowledge about cellular and molecular aspects of
      AM. Emphasis is placed on morphological changes in colonized cells, transfer of
      nutrients between both interacting partners, and plant defence responses.
      Similarities to and differences from other associations of plant and
      microorganisms are highlighted regarding defence reactions and signal perception.

PMID- 15871032
TI  - Structure, expression, and transcriptional regulation of the Strongylocentrotus
      franciscanus spec gene family encoding intracellular calcium-binding proteins.
AB  - The mechanisms by which gene expression patterns emerge during evolution are
      poorly understood. The sea urchin spec genes offer a useful means to investigate
      evolutionary mechanisms. Genes of the spec family from Strongylocentrotus
      purpuratus and Lytechinus pictus have identical patterns of aboral ectoderm
      specific expression but exhibit species-specific differences in copy number,
      genomic structure, temporal expression, and cis-regulatory architecture. Here, we
      identify spec genes from a phylogenetic intermediate, Strongylocentrotus
      franciscanus, to gain insight into the evolution of the spec gene family and its
      transcriptional regulation. We identified two spec genes in the S. franciscanus
      genome, sfspec1a and sfspec1b, that were orthologous to spec1 from S. purpuratus.
      sfspec1b transcripts began to accumulate at the blastula stage and became
      progressively more abundant; this was reminiscent of spec expression in L. pictus
      but different from that in S. purpuratus. As expected, sfspec1b expression was
      restricted to aboral ectoderm cells. The six-exon structure of the sfspec1b
      genomic locus was identical to that of the S. purpuratus spec genes and was
      bounded by two repeat-spacer-repeat (RSR) repetitive sequence elements, which are
      conserved features of S. purpuratus spec genes and function as transcriptional
      enhancers. The enhancer activity of the sfspec1b RSRs was comparable to that of
      their S. purpuratus counterparts, although the placement and orientation of
      crucial cis-regulatory elements within the RSRs differed. We discovered a spec
      gene in S. franciscanus that was only distantly related to other spec genes but
      was highly conserved in S. purpuratus. Unexpectedly, this gene was expressed
      exclusively in endoderm lineages. Our results show that the evolution of spec cis
      regulatory elements is highly dynamic and that substantial alterations can occur
      when maintaining or grossly modifying gene expression patterns.

PMID- 15871033
TI  - Cost-effectiveness of oral ibandronate compared with intravenous (i.v.)
      zoledronic acid or i.v. generic pamidronate in breast cancer patients with
      metastatic bone disease undergoing i.v. chemotherapy.
AB  - BACKGROUND: Ibandronate is the first third-generation bisphosphonate to have both
      oral and intravenous (i.v.) efficacy. An incremental cost-effectiveness model
      compared oral ibandronate with i.v. zoledronic acid and i.v. generic pamidronate
      in female breast cancer patients with metastatic bone disease, undergoing i.v.
      chemotherapy. METHODS: A global economic model was adapted to the UK National
      Health Service (NHS), with primary outcomes of direct healthcare costs and
      quality-adjusted life years (QALYs). Efficacy, measured as relative risk
      reduction of skeletal-related events (SREs), was obtained from clinical trials.
      Resource use data for i.v. bisphosphonates and the cost of managing SREs were
      obtained from published studies. Hospital management and SRE treatment costs were
      taken from unit cost databases. Monthly drug acquisition costs were obtained from
      the British National Formulary. Utility scores were applied to time with/without
      an SRE to adjust survival for quality of life. Model design and inputs were
      validated through expert UK clinician review. RESULTS: Total cost, including drug
      acquisition, was pound 386 less per patient with oral ibandronate vs. i.v.
      zoledronic acid and pound 224 less vs. i.v. generic pamidronate. Oral ibandronate
      gained 0.019 and 0.02 QALYs vs. i.v. zoledronic acid and i.v. pamidronate,
      respectively, making it the economically dominant option. At a threshold of pound
      30,000 per QALY, oral ibandronate was cost-effective vs. zoledronic acid in 85%
      of simulations and vs. pamidronate in 79%. CONCLUSIONS: Oral ibandronate is a
      cost-effective treatment for metastatic bone disease from breast cancer due to
      reduced SREs, bone pain, and cost savings from avoidance of resource use commonly
      associated with bisphosphonate infusions.

PMID- 15871034
TI  - Spectroscopic characteristics of the micro-environmentally induced H-bond
      transformation in anil-type species: experimental and theoretical study.
AB  - The results of combined experimental and theoretical investigations of the
      spectral behavior of anil-type systems are presented. Two species: N
      triphenylmethylsalicylidene imine (MS1) and N-salicylidene methylamine (SmA) were
      studied. The electronic (absorption, emission and excitation) spectra of MS1 at
      room temperature were investigated in pure isooctane as well as in acetonitrile
      and methanol solutions by the steady-state experiments. A mechanism of molecular
      processes in the ground and excited states in different microenvironments is also
      proposed. It includes formation of intra- and intermolecular hydrogen bonds,
      their role in stabilization of molecular conformations and conformation
      equilibria. The "solvent assisted" proton transfer reaction and rearrangement
      were modeled using complexes obtained by attaching methanol molecules to the
      species studied. The OH-rotamer of SmA was also considered. Infrared and Raman
      spectra were predicted for MS1 and SmA and compared with the experimental data.
      An analysis of fundamental vibration frequencies was carried out. Quantum
      chemical ab initio calculations at the HF/6-31G** level were performed for the
      species studied and their complexes. Chemical formula of anil-type compound: N
      salicylidene methylamine (SmA), N-salicylideneaniline (SA) and N
      triphenylmethylsalicylidene imine (MS1). [Structure: see text].

PMID- 15871035
TI  - DFT studies on isomerization reactions in the copolymerization of ethylene and
      methyl acrylate catalyzed by Ni-diimine and Pd-diimine complexes.
AB  - Gradient corrected density functional theory (DFT) has been used to investigate
      the isomerization reactions in the process of the ethylene/methyl acrylate
      copolymerization catalyzed by Pd-dimine and Ni-dimine complexes, modeled by a
      generic system NwedgeN-M-(CH3)+; NwedgeN=-N(H)-C(H)-C(H)-N(H)-. The influence of
      the polar group and of the metal on the isomerization mechanism was studied. The
      results show that for the Pd-catalyst the isomerization follows the standard
      mechanism observed in homopolymerization processes, with the beta-hydrogen
      transfer to the metal and formation of a pi-olefin-hydride complex. Electron
      withdrawing character of the polar group results in an increase of the hydride
      energy and the isomerization barrier. For the Ni-catalyst the overall
      isomerization picture is modified by the formation of a sigma-olefin-hydride
      complex, in which the olefin is coordinated to the metal by the oxygen atom of
      the polar group. Such a sigma-olefin-hydride is lower in energy for the Ni
      catalyst than the pi-olefin-hydride complex by 9.6 kcal mol(-1) . The latter is
      preferred by 2.6 kcal mol(-1) for the Pd-based system. The calculated
      isomerization barriers are 20.9 and 24.0 kcal mol(-1) (with respect to the
      initial 4-member chelate) for the Pd-catalyst and Ni-catalyst, respectively. This
      can result in a larger fraction of ester group directly connected to the
      copolymer backbone observed experimentally for the Ni-catalyst. [Figure: see
      text]. Structure of the four-membered and five-membered chelates formed after 2,1
      insertion of methyl acrylate into the metal-alkyl bond of the catalyst.

PMID- 15871037
TI  - Monocomponent endoglucanase treatment increases the reactivity of softwood
      sulphite dissolving pulp.
AB  - Softwood dissolving pulp was treated with a commercial monocomponent fungal
      endocellulase. The reactivity of the pulp for the production of rayon and
      cellulose derivatives as determined with the Fock method increased drastically
      with relatively low amounts of enzyme, and the yield loss and decrease of
      viscosity were moderate. The mechanism behind the increased reactivity is
      discussed.

PMID- 15871036
TI  - Comparison between biological and chemical treatment of wastewater containing
      nitrogen and phosphorus.
AB  - The present work compared chemical and biological treatment methods to achieve
      the most efficient treatment for the reduction or elimination of phosphorus and
      nitrogen from mixed industrial-domestic wastewaters. Batch chemical precipitation
      by ferric chloride and aluminum sulfate (alum) and a continuous biological
      suspended growth system were investigated as well as the optimum operating
      conditions. Concerning chemical treatment, Alum generally achieved a higher
      removal efficiency percentage for the investigated pollutants compared with
      FeCl(3) at their optimum pH and dose, especially with chemical oxygen demand
      (COD). FeCl(3) treatment achieved success only with phosphorus removal, while
      none of the COD, 5-day biochemical oxygen demand (BOD(5)), total nitrogen (TN)
      and N-NH(3) achieved acceptable treatment and remained above the maximum
      permissible limits (MPL). Thus, for such wastewaters, alum is more efficient than
      FeCl(3). Biological treatment exhibited higher efficiencies, particularly towards
      nitrogen. TN removal increased by increasing the flow rate to 30-60 l/day. N
      NH(3) removal was effective at the slowest flow rate and decreased with
      increasing flow rate, while an opposite trend was recorded for N-NO(3). At all
      flow rates, phosphorus levels were below the accepted MPL for discharging into
      natural systems. Moreover, there was a general trend for the proposed biological
      treatment to achieve a high removal efficiency for BOD(5) and COD, bringing them
      to acceptable levels to be released into watercourses safely, especially at the
      slowest flow rates. Thus, integration between the proposed chemical and
      biological treatment is highly recommended, producing high-quality effluents
      acceptable by the environmental law.

PMID- 15871038
TI  - Foraging behaviour in domestic pigs (Sus scrofa): remembering and prioritizing
      food sites of different value.
AB  - This experiment investigated whether domestic pigs can remember the locations of
      food sites of different relative value, and how a restricted retrieval choice
      affects their foraging behaviour. Nine juvenile female pigs were trained to
      relocate two food sites out of a possible eight in a spatial memory task. The two
      baited sites contained different amounts of food and an obstacle was added to the
      smaller amount to increase handling time. On each trial, a pig searched for the
      two baited sites (search visit). Once it had found and eaten the bait, it
      returned for a second (relocation) visit, in which the two same sites were
      baited. Baited sites were changed between trials. All subjects learnt the task.
      When allowed to retrieve both baits, the subjects showed no preference for
      retrieving a particular one first (experiment 1). When they were allowed to
      retrieve only one bait, a significant overall preference for retrieving the
      larger amount emerged across subjects (experiment 2). To test whether this
      preference reflected an avoidance of the obstacle with the smaller bait, 15
      choice-restricted control trials were conducted. In control trials obstacles were
      present with both baits. Pigs continued to retrieve the larger bait, indicating
      they had discriminated between the two food sites on the basis of quantity or
      profitability and adjusted their behaviour accordingly when the relocation choice
      was restricted. This suggests for the first time that domestic pigs have the
      ability to discriminate between food sites of different relative value and to
      remember their respective locations.

PMID- 15871039
TI  - Evolutionary relationships of the limnochromini, a tribe of benthic deepwater
      cichlid fish endemic to Lake Tanganyika, East Africa.
AB  - Lake Tanganyika harbors an enormous diversity of cichlid fish that stem from
      eight distinct ancestral lineages, which colonized the lake after its formation 9
      to 12 million years ago. Six of twelve currently described tribes are assigned to
      the "H-lineage," an assemblage of exclusively mouthbrood-ing cichlids, all of
      which evolved during a short period of time during the course of the primary
      radiation of lacustrine species. Our study focuses on the deepwater tribe
      Limnochromini, comprising bi-parental mouthbrooders, and is based on phylogenetic
      analysis of two mitochondrial gene segments. We confirm the polyphyletic origin
      of the Limnochromini as they are defined to date, in that Gnathochromis pfefferi
      is placed among the Tropheini, whereas the genus Benthochromis is presented as an
      independent lineage. The remaining nine species were unambiguously resolved as
      monophyletic and should be redefined as the tribe Limnochromini. Concerning
      generic assignments, the genus Greenwoodochromis appeared as monophyletic,
      Limnochromis as paraphyletic, and the genera Reganochromis and Baileychromis as
      monophyletic sister genera. The linearized tree analysis and the comparison of
      average sequence divergences to that of the remaining tribes of the H-lineage
      revealed a relatively recent but simultaneous proliferation of the Limnochromini,
      suggesting that the same environmental changes triggered the radiation of
      particular deepwater, benthic, pelagic, and littoral lineages. By using a
      preliminary calibration of a molecular clock based on gamma-corrected amino acid
      distances of the NADH2 gene, the diversification of the Limnochromini could
      tentatively be dated to 2.9-3.5 MYA, coinciding with a period of aridification in
      East Africa between 2.5 and 3 MYA. The lack of geographic color morphs and the
      structural uniformity and resource scarcity of deepwater habitats suggest that
      competition and resource partitioning leading to differential trophic
      specialization promoted speciation within the Limnochromini, rather than an
      allopatric model.

PMID- 15871040
TI  - Why are young and old repetitive elements distributed differently in the human
      genome?
AB  - Alu elements are not distributed homogeneously throughout the human genome: old
      elements are preferentially found in the GC-rich parts of the genome, while young
      Alus are more often found in the GC-poor parts of the genome. The process giving
      rise to this differential distribution remains poorly understood. Here we
      investigate whether this pattern could be due to a preferential degradation of
      Alu elements integrated in GC-poor regions by small indel mutations. We aligned
      5.1 Mb of human and chimpanzee sequences and examined whether the rate of
      insertion and deletion inside Alu elements differed according to the base
      composition surrounding them. We found that Alu elements are not preferentially
      degraded in GC-poor regions by indel events. We also looked at whether very young
      L1 elements show the same change in distribution compared to older ones. This
      analysis indicated that L1 elements also show a shift in their distribution,
      although we could not assess it as precisely as for Alu elements. We propose that
      the differential distribution of Alu elements is likely to be due to a change in
      their pattern of insertion or their probability of fixation through evolutionary
      time.

PMID- 15871041
TI  - Ancient divergence in bathypelagic lake tanganyika deepwater cichlids:
      mitochondrial phylogeny of the tribe bathybatini.
AB  - The cichlid species flock of Lake Tanganyika represents a polyphyletic assemblage
      of eight ancestral lineages, which colonized the emerging lake independently. Our
      study is focused on one of these lineages, the Bathybatini, a tribe of
      specialized piscivorous cichlids of the deep pelagic zone. By analyzing three
      mtDNA gene segments of all eight species of the tribe and two species of the
      closely related Trematocarini, we propose on the basis of a linearized tree
      analysis that the Bathybatini comprise two distinct lineages, the genera
      Hemibates and Bathybates, that seeded the primary lacustrine Tanganyika radiation
      independently. The genus Hemibates is likely to represent a distinct lineage that
      emerged simultaneously with the tribe Trematocarini and the genus Bathybates and
      should be therefore treated as a distinct tribe. Within the genus Bathybates, B.
      minor clearly represents the most ancestral split and is likely to have diverged
      from the remaining species in the course of the "primary lacustrine Tanganyika
      radiation" during which also the radiations of the Lamprologini and the H-lineage
      took place. The remaining "large" Bathybates species also diversified almost
      simultaneously and in step with the diversification of other Tanganyikan lineages
      the Limnochromini and Cyprichromini-with B. graueri occupying the most ancestral
      branch, suggesting that these were induced by the same environmental changes. The
      lack of geographic color morphs suggests that competition and resource
      partitioning, rather than allopatric speciation, promoted speciation within the
      genus Bathybates.

PMID- 15871042
TI  - Detecting site-specific physicochemical selective pressures: applications to the
      Class I HLA of the human major histocompatibility complex and the SRK of the
      plant sporophytic self-incompatibility system.
AB  - Models of codon substitution are developed that incorporate physicochemical
      properties of amino acids. When amino acid sites are inferred to be under
      positive selection, these models suggest the nature and extent of the
      physicochemical properties under selection. This is accomplished by first
      partitioning the codons on the basis of some property of the encoded amino acids.
      This partition is used to parametrize the rates of property-conserving and
      property-altering base substitutions at the codon level by means of finite
      mixtures of Markov models that also account for codon and transition:transversion
      biases. Here, we apply this method to two positively selected receptors involved
      in ligand-recognition: the class I alleles of the human major histocompatibility
      complex (MHC) of known structure and the S-locus receptor kinase (SRK) of the
      sporophytic self-incompatibility system (SSI) in cruciferous plants
      (Brassicaceae), whose structure is unknown. Through likelihood ratio tests we
      demonstrate that at some sites, the positively selected MHC and SRK proteins are
      under physicochemical selective pressures to alter polarity, volume, polarity
      and/or volume, and charge to various extents. An empirical Bayes approach is used
      to identify sites that may be important for ligand recognition in these proteins.

PMID- 15871043
TI  - ITS-2 and 18S rRNA gene phylogeny of Aplysinidae (Verongida, Demospongiae).
AB  - 18S ribosomal DNA and internal transcribed spacer 2 (ITS-2) full-length
      sequences, each of which was sequenced three times, were used to construct
      phylogenetic trees with alignments based on secondary structures, in order to
      elucidate genealogical relationships within the Aplysinidae (Verongida). The
      first poriferan ITS-2 secondary structures are reported. Altogether 11 Aplysina
      sponges and 3 additional sponges (Verongula gigantea, Aiolochroia crassa,
      Smenospongia aurea) from tropical and subtropical oceans were analyzed. Based on
      these molecular studies, S. aurea, which is currently affiliated with the
      Dictyoceratida, should be reclassified to the Verongida. Aplysina appears as
      monophyletic. A soft form of Aplysina lacunosa was separated from other Aplysina
      and stands at a basal position in both 18S and ITS-2 trees. Based on ITS-2
      sequence information, the Aplysina sponges could be distinguished into a single
      Caribbean-Eastern Pacific cluster and a Mediterranean cluster. The species
      concept for Aplysina sponges as well as a phylogenetic history with a possibly
      Tethyan origin is discussed.

PMID- 15871044
TI  - Decoding the decoding region: analysis of eukaryotic release factor (eRF1) stop
      codon-binding residues.
AB  - Peptide synthesis in eukaryotes terminates when eukaryotic release factor 1
      (eRF1) binds to an mRNA stop codon and occupies the ribosomal A site. Domain 1 of
      the eRF1 protein has been implicated in stop codon recognition in a number of
      experimental studies. In order to further pinpoint the residues of this protein
      involved in stop codon recognition, we sequenced and compared eRF1 genes from a
      variety of ciliated protozoan species. We then performed a series of
      computational analyses to evaluate the conservation, accessibility, and
      structural environment of each amino acid located in domain 1. With this new
      dataset and methodology, we were able to identify eight specific amino acid sites
      important for stop codon recognition and also to propose a set of cooperative
      paired substitutions that may underlie stop codon reassignment. Our results are
      more consistent with current experimental data than previously described models.

PMID- 15871045
TI  - Site-specific evolutionary rate inference: taking phylogenetic uncertainty into
      account.
AB  - The evolutionary rate at an amino acid site is indicative of how conserved this
      site is and, in turn, allows evaluating the importance of this site in
      maintaining the structure/function of the protein. When evolutionary rates are
      estimated, one must reconstruct the phylogenetic tree describing the evolutionary
      relationship among the sequences under study. However, if the inferred
      phylogenetic tree is incorrect, it can lead to erroneous site-specific rate
      estimates. Here we describe a novel Bayesian method that uses Markov chain Monte
      Carlo methodology to integrate over the space of all possible trees and model
      parameters. By doing so, the method considers alternative evolutionary scenarios
      weighted by their posterior probabilities. We show that this comprehensive
      evolutionary approach is superior over methods that are based on only a single
      tree. We illustrate the potential of our algorithm by analyzing the conservation
      pattern of the potassium channel protein family.

PMID- 15871046
TI  - The hydrophobicity of the H3 histone fold differs from the hydrophobicity of the
      other three folds.
AB  - The eukaryotic histone dimers, H3-H4 and H2A-H2B, are formed in the cytosol prior
      to being transported into the nucleus and assembled into the nucleosome. Residue
      side-chain distances from the interior of the histone dimers are obtained with an
      ellipsoidal spatial metric and structural information provided by X-ray analyses
      at atomic resolution of the nucleosome core particles. While the spatial
      hydrophobic moment profiles of the dimers are comparable with profiles obtained
      previously that characterize the hydrophobic core of single-chain, single-domain
      globular soluble proteins, correlation coefficients between the side-chain
      hydrophobicities and distances from the interior of the H3-H4 dimer and H2A-H2B
      dimer differ significantly. This difference is traced to the H3 histone fold,
      which segregates fewer hydrophobic residues within the protein interior than the
      three other folds. Examination of the correlation coefficient between residue
      hydrophobicity and side-chain distance from the dimer interior over local regions
      of the fold sequence shows that the region of reduced correlation is associated
      mainly with the residues at the carboxyl end of the H3 histone fold, the helical
      region of the fold involved in the H3-H3' binding of the (H3-H4)(2) tetramer of
      the nucleosome. Hydrophobic interactions apparently contribute to the binding of
      this fourfold helical bundle and this evolutionary requirement may trade off
      against the requirement for H3-H4 dimer stability. The present results provide a
      different view than previously proposed, albeit of similar origin, to account for
      the reduced stability of the H3-H4 dimer compared with the H2A-H2B dimer.

PMID- 15871047
TI  - The biased distribution of Alus in human isochores might be driven by
      recombination.
AB  - Alu retrotransposons do not show a homogeneous distribution over the human genome
      but have a higher density in GC-rich (H) than in AT-rich (L) isochores. However,
      since they preferentially insert into the L isochores, the question arises: What
      is the evolutionary mechanism that shifts the Alu density maximum from L to H
      isochores? To disclose the role played by each of the potential mechanisms
      involved in such biased distribution, we carried out a genome-wide analysis of
      the density of the Alus as a function of their evolutionary age, isochore
      membership, and intron vs. intergene location. Since Alus depend on the
      retrotransposase encoded by the LINE1 elements, we also studied the distribution
      of LINE1 to provide a complete evolutionary scenario. We consecutively check, and
      discard, the contributions of the Alu/LINE1 competition for retrotransposase,
      compositional matching pressure, and Alu overrepresentation in introns. In
      analyzing the role played by unequal recombination, we scan the genome for Alu
      trimers, a direct product of Alu-Alu recombination. Through computer simulations,
      we show that such trimers are much more frequent than expected, the
      observed/expected ratio being higher in L than in H isochores. This result,
      together with the known higher selective disadvantage of recombination products
      in H isochores, points to Alu-Alu recombination as the main agent provoking the
      density shift of Alus toward the GC-rich parts of the genome. Two independent
      pieces of evidence-the lower evolutionary divergence shown by recently inserted
      Alu subfamilies and the higher frequency of old stand-alone Alus in L isochores
      support such a conclusion. Other evolutionary factors, such as population
      bottlenecks during primate speciation, may have accelerated the fast accumulation
      of Alus in GC-rich isochores.

PMID- 15871048
TI  - The origin and evolution of operons: the piecewise building of the
      proteobacterial histidine operon.
AB  - The structure and organization of 470 histidine biosynthetic genes from 47
      different proteobacteria were combined with phylogenetic inference to investigate
      the mechanisms responsible for assembly of the his pathway and the origin of his
      operons. Data obtained in this work showed that a wide variety of different
      organization strategies of his gene arrays exist and that some his genes or
      entire his operons are likely to have been horizontally transferred between
      bacteria of the same or different proteobacterial branches. We propose a
      "piecewise" model for the origin and evolution of proteobacterial his operons,
      according to which the initially scattered his genes of the ancestor of
      proteobacteria coded for monofunctional enzymes (except possibly for hisD) and
      underwent a stepwise compacting process that reached its culmination in some
      gamma-proteobacteria. The initial step of operon buildup was the formation of the
      his "core," a cluster consisting of four genes (hisBHAF) whose products
      interconnect histidine biosynthesis to both de novo synthesis of purine
      metabolism and that occurred in the common ancestor of the alpha/beta/gamma
      branches, possibly after its separation from the epsilon one. The following step
      was the formation of three mini-operons (hisGDC, hisBHAF, hisIE) transcribed from
      independent promoters, that very likely occurred in the ancestor of the
      beta/gamma-branch, after its separation from the alpha one. Then the three mini
      operons joined together to give a compact operon. In most gamma-proteobacteria
      the two fusions involving the gene pairs hisN-B and hisI-E occurred. Finally the
      gamma-proteobacterial his operon was horizontally transferred to other
      proteobacteria, such as Campylobacter jejuni. The biological significance of
      clustering of his genes is also discussed.

PMID- 15871049
TI  - Reduced rates of sequence evolution of Y-linked satellite DNA in Rumex
      (Polygonaceae).
AB  - One characteristic of sex chromosomes is the accumulation of a set of different
      types of repetitive DNA sequences in the Y chromosomes. However, little is known
      about how this occurs or about how the absence of recombination affects the
      subsequent evolutionary fate of the repetitive sequences in the Y chromosome.
      Here we compare the evolutionary pathways leading to the appearance of three
      different families of satellite-DNA sequences within the genomes of Rumex acetosa
      and R. papillaris, two dioecious plant species with a complex XX/XY(1)Y(2) sex
      chromosome system. We have found that two of these families, one autosomic (the
      RAE730 family) and one Y-linked (the RAYSI family), arose independently from the
      ancestral duplication of the same 120-bp repeat unit. Conversely, a comparative
      analysis of the three satellite-DNA families reveals no evolutionary
      relationships between these two and the third, RAE180, also located in the Y
      chromosomes. However, we have demonstrated that, regardless of the mechanisms
      that gave rise to these families, satellite-DNA sequences have different
      evolutionary fates according to their location in different types of chromosomes.
      Specifically, those in the Y chromosomes have evolved at half the rate of those
      in the autosomes, our results supporting the hypothesis that satellite DNAs in
      nonrecombining Y chromosomes undergo lower rates of sequence evolution and
      homogenization than do satellite DNAs in autosomes.

PMID- 15871050
TI  - The population genetics of the alpha-2 globin locus of orangutans (Pongo
      pygmaeus).
AB  - In this study, the molecular population genetics of the orangutan's alpha-2
      globin (HBA2) gene were investigated in order to test for the action of natural
      selection. Haplotypes from 28 orangutan chromosomes were collected from a 1.46
      kilobase region of the alpha-2 globin locus. While many aspects of the data were
      consistent with neutrality, the observed heterogeneous distribution of
      polymorphisms was inconsistent with neutral expectations. Furthermore, a single
      amino acid variant, found in both the Bornean and the Sumatran orangutan
      subspecies, was associated with different alternative synonymous variants in each
      subspecies, suggesting that the allele may have spread separately through the two
      subspecies after two distinct origination events. This variant is not in Hardy
      Weinberg equilibrium (HWE). These observations are consistent with neutral models
      that incorporate population structure and models that invoke selection. The
      orangutan Plasmodium parasite is a plausible selective agent that may underlie
      the variation at alpha-2 globin in orangutans.

PMID- 15871052
TI  - Application of a rapid non-invasive technique in the molecular diagnosis of
      spinal muscular atrophy (SMA).
AB  - BACKGROUND AND PURPOSE: Proximal spinal muscular atrophy (SMA) is an autosomal
      recessive disorder caused by mutations of the SMN1 gene. The most frequent
      mutation is biallelic deletion of exon 7 of the SMN1 gene. A small percentage of
      SMA patients present compound heterozygosity with a point mutation on one allele
      and deletion on the other. In the remaining cases the disease is unlikely to be
      related to SMN1 defects. The aim of our study was to estimate the frequency of
      the common biallelic exon 7 SMN1 deletion in our Polish SMA cohort and implement
      a test for assessing a molecular defect at the SMN1 locus versus defects in the
      other genes. MATERIAL AND METHODS: The molecular analysis was performed in a
      group of 269 patients fulfilling diagnostic criteria of the International SMA
      Consortium. The common SMN1 exon 7 deletion was tested by a standard PCR
      analysis. Patients lacking the common mutation were subsequently analyzed for a
      number of SMN1 alleles with a quantitative test based on real-time PCR. RESULTS:
      The frequency of homozygous loss of exon 7 in the SMN1 gene was 96.6% (260/269)
      in our Polish SMA cohort. In 5 of 9 non-deleted patients the real-time PCR
      analysis showed a decreased number of SMN1 copies. We anticipate that the non
      deleted allele carries a second mutation in SMN1 which may contribute to the
      pathogenesis of SMA. We have also identified 4 patients (1.5%) with SMA carrying
      two SMN1 alleles without the exon 7 deletion. CONCLUSIONS: The molecular analysis
      of the biallelic exon 7 of the SMN1 deletion is a standard and reliable test in
      cases of SMA. Introduction of a quantitative test based on "real-time PCR"
      further enhances the diagnostic potential by increasing the detection rate of
      cases likely to be caused by point mutation of the SMN1 gene.

PMID- 15871051
TI  - Novel chaperonins in a prokaryote.
AB  - Group II chaperonins belong to the Hsp60 family occurring in archaea and
      eukaryotes. The archaeal chaperonins build the thermosome, which is similar to
      the eukaryotic CCT (chaperonin-containing TCP-1). Eukaryotes have eight subunits,
      and up until now, it was thought that archaea had between one and three subunits,
      depending on the species. We now report two novel subunits, termed Hsp60-4 and
      Hsp60-5, in the archaeon Methanosarcina acetivorans, which also has Hsp60-1,
      Hsp60-2, and Hsp60-3 with orthologs in Methanosarcinae. Hsp60-4 and Hsp60-5 occur
      only in M. acetivorans, which makes this organism unique in that it has the
      highest number of chaperonin subunits ever described for an archaeon.
      Evolutionary analysis suggests that either Hsp60-4 or Hsp60-5 paralogs have
      arisen by gene duplication with vastly increased accepted substitution rates or
      that they represent ancestral types found only in this species.

PMID- 15871053
TI  - [Treatment of deep brain arteriovenous malformations].
AB  - BACKGROUND AND PURPOSE: The results of the treatment of patients with deep,
      supratentorial arteriovenous malformations (AVMs) located in medial hemisphere or
      intraventricularly are presented. MATERIAL AND METHODS: The paper presents the
      results of treatment of 17 patients. AVMs were located in the trigonum of the
      lateral ventricle in 4 cases (23.5%), in the splenium of the corpus callosum and
      its neighborhood in 4 cases (23.5%), in the parahippocampal and lingual gyrus in
      3 cases (17%), in the head of the caudate nucleus in 2 cases (12%), in the
      hippocampus and the nucleus amygdalae in 2 cases (12%), in the anterior part of
      the gyrus cinguli in 1 case (6%) and in the truncus of the corpus callosum in 1
      case (6%). RESULTS: AVMs most often manifested as intracerebral or subarachnoid
      hemorrhage (82%). The surgical treatment has been applied (total removal--90%),
      embolization with histoacryl glue (total embolization--20%) and irradiation with
      LINAC. The surgical treatment was performed in all patients with hemiparesis and
      intracerebral hematomas. CONCLUSION: The results of the surgical treatment are
      good and it fastest prevents recurrent hemorrhage from deep AVM. Incomplete
      embolization of AVM without the surgical treatment or radiosurgery is life
      threatening for the patients.

PMID- 15871054
TI  - [The use of neuroendoscopy in the treatment of intraventricular and
      paraventricular brain tumors].
AB  - BACKGROUND AND PURPOSE: Because of their deep location, intra- and para-
      ventricular brain tumors pose an important therapeutic issue. Technical
      difficulties during the operation often result from the alteration of anatomy
      produced by the tumor, which brings about the risk of injury to functionally
      important structures. The authors assess clinical usefulness of neuroendoscopy in
      the treatment of discussed tumors. MATERIAL AND METHODS: Medical records of 16
      adult patients treated between 2000 and 2003 were analyzed. The diagnosis was
      based on CT with 3D reconstruction and MRI. In 7 cases the tumor was located in
      the third ventricle, in 4--in lateral ventricles, in 5--paraventricularly.
      Surgery was performed using a rigid neuroendoscope and/or neurofiberscope
      equipped with the basic set of endoscopic instruments. The efficacy of the
      procedure was evaluated by clinical, CT and MRI follow-up examinations. The
      intended and achieved aim of the operation as well as the remote outcome were
      analyzed. RESULTS: The planned aim of the procedure was achieved in 12 (75%)
      patients. In 3 cases the tumor was removed totally, in 5--tumor mass was reduced
      restoring the cerebro-spinal fluid passage, in 4--tumor biopsy was performed. In
      4 patients different obstacles made it impossible to achieve the intended aim of
      the procedure. 1 patient died in the direct postoperative course. In the long
      term postoperative follow-up ranging from 8 to 44 months (median: 23 months), the
      clinical condition improved or was stable in 10 patients, 2 patients were
      reoperated, 2 became dependent and 1 was lost for follow-up. CONCLUSIONS:
      Neuroendoscopy offers new options in the treatment of intraventricular and
      paraventricular brain tumors allowing for their removal, reduction,
      histopathological verification and restoration of the cerebrospinal fluid
      passage. The outcome is good with a low complication rate.

PMID- 15871055
TI  - [Interferon gamma concentration in the cerebrospinal fluid of patients with tick
      borne encephalitis].
AB  - BACKGROUND AND PURPOSE: The purpose of this work was to evaluate interferon gamma
      (IFN-g) concentration in the cerebrospinal fluid of patients with diagnosed tick
      borne encephalitis (TBE) early in the course of the disease and after the
      treatment. MATERIAL AND METHODS: The cerebrospinal fluid of 40 patients with TBE
      was examined. Patients were divided into 4 groups: group 1 consisted of 13
      patients with mild clinical course, group 2 included 12 patients with prolonged
      TBE showing the presence of inflammatory markers after the treatment, group 3
      comprised 9 patients with severe TBE presenting with disorders of consciousness
      and group 4 consisted of 6 patients with a simultaneous B. burgdorferi infection.
      The cerebrospinal fluid was examined twice--during TBE diagnosing and after the
      treatment. IFN-g was detected by the ELISA method. RESULTS: The concentration of
      IFN-g in the cerebrospinal fluid in the first examination was significantly
      higher in all four groups of patients in comparison with controls. After the
      treatment, concentration of IFN-g decreased significantly in all studied groups.
      The highest concentration of IFN-g at the first examination was found in group 3.
      The concentration of IFN-g at the second examination was similar among 4 groups
      of patients and in controls. CONCLUSIONS: We found the correlation between IFN-g
      concentration in the cerebrospinal fluid of patients at the early stage of TBE
      and inflammation activity. We did not find any association between IFN-g
      concentration and a persistent increase of the cerebrospinal fluid parameters.

PMID- 15871056
TI  - [Surgical treatment of degenerative lumbar spondylolisthesis].
AB  - BACKGROUND AND PURPOSE: Degenerative lumbar spondylolisthesis occurs most often
      at the L4-L5 level and is characterized by anterior displacement of L4 vertebra
      on L5 vertebra. The aim of the study is to present both the decompression of
      nerve elements of the vertebral canal and the method of spine internal
      stabilization in patients with degenerative lumbar spondylolisthesis. MATERIAL
      AND METHODS: Clinical analysis comprises 11 patients treated surgically because
      of the degenerative spondylolisthesis. Intervertebral dislocation of more than
      20% included 4 patients where the vertebral column stabilization was achieved by
      transpedicular stabilization as well as intervertebral and posterolateral spinal
      fusion (group I). In spondylolisthesis of less than 20% (4 patients)
      spondylodesis with intervertebral cages and posterolateral osseous grafts were
      carried out (group II). In the remaining 3 cases spondylolisthesis was smaller
      than 20% with denivelation of the intervertebral space (group III). There were
      nervous structures deliberated and spondylodesis was unnecessary. RESULTS: Low
      back pain and sciatic neuralgia were relieved in 9 (82%) patients. Neurological
      deficits were subsided completely in 7 (78%) cases. CONCLUSIONS: The evaluation
      of the degree of vertebral displacement, height of the intervertebral space and
      assessment of vertebral column stability allowed to determine the strategy of
      surgery in patients with degenerative lumbar spondylolisthesis.

PMID- 15871057
TI  - [Early neurological complications after internal carotid endarterectomy].
AB  - BACKGROUND AND PURPOSE: Stenosis of internal carotid arteries is one of the
      leading causes of ischemic stroke. Surgical restoration of arterial patency is
      the primary therapeutic method, aimed to prevent future ischemic stroke. This
      treatment mode is mainly reserved for patients with recurrent stenoses of
      internal carotid artery. Endarterectomy of internal carotid artery poses some
      risk of complications, and neurological complications are among the most
      dangerous ones. The purpose of the study was to assess early neurologic
      complications after surgical reopening of the affected arteries. MATERIAL AND
      METHODS: The study included 119 patients being operated because of critical
      stenosis of an internal carotid artery in the Department of General and Vascular
      Surgery of the Provincial Specialist Hospital in Olsztyn between 1999 and 2003.
      The main indications for surgical treatment were episodes of sustained cerebral
      ischemia and stenosis of an internal carotid artery exceeding 70%, documented
      with the ultrasound or angiographic examination. RESULTS: Neurologic
      complications occurred in 16 patients (12%). Ischemic stroke occurred in 6 cases,
      transient ischemic attacks in 4 cases, acute cerebral hyperemia in one case and
      four patients suffered from transient cranial nerve palsy. The most important
      risk factors of complications were: a previous episode of cerebral ischemia,
      significant stenosis of a contralateral artery, nicotinism, arterial hypertension
      and coronary artery disease. Females are exposed to a significantly greater risk
      of complications. CONCLUSIONS: Surgical reopening of internal carotid arteries is
      a relatively safe therapeutic method with a modest risk of neurological
      complications, with the most dangerous and potentially lethal ischemic stroke
      occurring relatively rarely.

PMID- 15871058
TI  - [Cognitive impairment in multiple sclerosis].
AB  - In this article we present a review of problems associated with cognitive
      dysfunctions in multiple sclerosis (MS). Neuropsychological investigations
      demonstrated that cognitive dysfunctions are common in MS patients and affect 40
      65% of them. Cognitive deficits were found mainly on measures of memory,
      attention, information-processing speed, executive functions and abstract
      reasoning. The differences and degree of cognitive dysfunctions in MS are
      highlighted and usually related to different clinical appearance (clinical
      course, duration, disability level, treatment type). Furthermore, we have
      reviewed published correlations between psychopathological dysfunctions and
      neuroimaging results (mainly MRI techniques and functional imaging). The results
      of these correlations showed that an important role in cognitive impairment is
      related to the total lesion area, the severity of the pathological damage of the
      normal-appearing brain tissue (NABT), and brain atrophy.

PMID- 15871059
TI  - [Atrial fibrillation as a relevant risk factor for stroke].
AB  - Atrial fibrillation, one of the most frequent heart rhythm disturbances and the
      most common source of embolic material in cerebral circulation, is associated
      with a fivefold increased risk of ischemic stroke. Except thromboembolic
      complications, atrial fibrillation affects hemodynamic activity of the heart,
      reduces cardiac output and might decrease cerebral blood flow. It is possible
      that atrial fibrillation disturbs autoregulation mechanisms of cerebral
      circulation in patients suffering from an acute stroke. This could be the reason
      of higher early mortality and more severe clinical outcome versus strokes in
      patients with the sinus rhythm. An ongoing increase of population with atrial
      fibrillation is observed. Such patients often need intensive antithrombotic
      prevention with oral anticoagulants. Worldwide prescribing effective
      anticoagulant therapy is insufficient in relation to the needs. The leading
      reason underlying the under-utilization of oral anticoagulation in patients with
      atrial fibrillation is the lack of knowledge about importance of this kind of
      stroke prevention and fear of bleeding among doctors, particularly among general
      practitioners.

PMID- 15871060
TI  - [Motor variant of the unilateral neglect syndrome as a consequence of brain
      injury].
AB  - Motor neglect is characterized by underutilization of one side of the body when
      this failure cannot be attributed to primary sensory and motor defects. Impaired
      motor activity manifests itself in disturbance of using spontaneously
      contralesional limbs in the absence of severe hemiplegia (motor neglect) or in
      reduced readiness to initiate and carry out intact ipsilesional arm movements
      within or towards the contralesional hemispace (pre-motor neglect). These
      specific higher-order motor deficits may occur in isolation (pure motor neglect)
      or as part of a more pervasive neglect syndrome involving disturbances in visual,
      auditory, and tactile modalities or even in mental images. The lesions underlying
      the motor variant of hemi-neglect are ascribed to various topographic sites of
      the brain involving cortical and subcortical structures of the right or, rarely,
      the left hemisphere. Motor features of neglect are more frequent, more severe and
      long-lasting in right--as compared with left--brain-damaged patients. This
      deficit additionally makes improvement and neurorehabilitation of patients with
      focal brain damage difficult.

PMID- 15871061
TI  - [Minimally invasive percutaneous transpedicular lumbar spine fixation. Operative
      technique and a case report].
AB  - Transpedicular fixation systems are commonly used in lumbar spine surgery for the
      treatment of a variety of pathologies making the solid fusion of operated spinal
      segments possible. Recently there has been a big interest in minimally invasive
      techniques in spinal surgery, including minimally invasive fixation systems. By
      minimizing the operative trauma minimally invasive techniques allow patients to
      restore activity faster. In the paper the authors present the Sextant system
      (Medtronic Sofamor Danek), which provides minimally invasive (percutaneous)
      fixation. Before fixing the spine, it is necessary to perform discectomy and
      interbody fusion using the PLIF or ALIF method. The authors present the system,
      describe the operative technique, and present a case of the patient with L4/L5
      spondylolisthesis successfully treated using this technique.

PMID- 15871062
TI  - [Abduction of the eyeballs palsy as a first sign of subarachnoid hemorrhage from
      ruptured posterior inferior cerebellar artery aneurysm: a case report].
AB  - The authors present a rare case of the abduction of the eyeballs palsy caused by
      subarachnoid hemorrhage from ruptured posterior-inferior cerebellar artery
      aneurysm, which appeared as a first sign of hemorrhage. Aneurysm was clipped.
      During three days after the operation, oculomotor lesions appeared persistent, no
      consciousness deterioration or other focal signs were observed. On the third day
      after the operation asystolic cardiac arrest appeared. Control CT scan did not
      reveal any pathological changes responsible for such deterioration. The patient
      died. In our case after an analysis of the mechanism and pathophysiology of this
      lesion in our opinion that palsy might be caused by influence of extravasated
      blood after hemorrhage. This thesis is adequate to the reviewed literature on
      this problem. Nevertheless, the compression of the abducent nerve as the reason
      cannot be excluded, e.g. rapid enlargement of the aneurysm or the compression of
      the brain stem near the nerve. Posthemorrhagic lesion of the brain stem may have
      been the reason of this lesion, caused by penetration of the blood into the
      ventricle during subarachnoidal hemorrhage. Although these lesions are very rare,
      subarachnoid hemorrhage should be taken into consideration when the patient with
      eyeballs abduction palsy is admitted to a neurosurgical or neurological
      department.

PMID- 15871063
TI  - [Migraine with a combination of aura symptoms as a clinical manifestation of
      cortical spreading depression].
AB  - The pathomechanism of the migraine aura remains unclear. The most probable cause
      of the aura is cortical spreading depression with associated hypoperfusion. Both
      the cortical spreading depression and hypoperfusion begin in the occipital lobes
      and spread forward slowly (2-3 mm/min) in a wave-like mode along the brain
      convolutions and cross territories of brain arteries. We present a 24-year-old
      female patient with a combination of aura symptoms. Each migraine attack began
      with a bright scintillating zig-zag, which crossed the visual field. It was
      followed by left sided hemiparesthesiae marching from the face to the hand. The
      last symptom of aura was motor aphasia. Later a unilateral, pulsating headache
      developed with associated photo- and phonophobia. The stable pattern and duration
      of aura symptoms in the presented case suggest that the cortical spreading
      depression plays an important role in the pathomechanism of migraine with aura.

PMID- 15871064
TI  - [Report from the 4th Central European Workshop of Microsurgery].

PMID- 15871065
TI  - [Is 18F-FDG-PET suitable for therapy monitoring after palliative photodynamic
      therapy of non-resectable hilar cholangiocarcinoma?].
AB  - BACKGROUND: If existing biliary drainage is insufficient, photodynamic therapy
      (PDT, laser treatment after application of a photosensitizer) is an already
      established adjunct to palliative therapy for progressing hilar
      cholangiocarcinoma (Klatskin tumours), since it prolongs survival and improves
      quality of life. Experimental studies of other tumour entities showed that (18)F
      FDG-PET ( (18)F-fluorodeosxyglucose-positron emission tomography) may play a role
      in monitoring tumour response to PDT. Furthermore, previous studies have revealed
      a high accuracy of this method for the detection of hilar cholangiocarcinoma.
      Therefore, the aim of the present study was to investigate the feasibility of
      (18)F-FDG-PET as a follow-up screening method in patients with hilar
      cholangiocarcinoma who underwent PDT. PATIENTS AND METHODS: 10 patients were
      examined by (18)F-FDG-PET before and 4 - 6 weeks after PDT. The following
      parameters were evaluated: maximum and mean SUV in the tumour, the ratio of
      maximum SUV in the tumour and mean SUV in the liver, the vital tumour volume, as
      well as bilirubin and CA 19 - 9 levels. RESULTS: All tumours were detected by
      (18)F-FDG-PET. Within a period of 4 - 6 weeks after PDT the cholestasis parameter
      bilirubin decreased significantly. However, SUV-associated parameters did not
      show a significant change after treatment while the estimated vital tumour volume
      even increased. DISCUSSION: PDT does not effect a relevant reduction of tumour
      mass in non-resectable hilar cholangiocarcinoma. However, PDT leads to a
      significant reduction of cholestasis. If (18)F-FDG-PET is suitable for monitoring
      the effect of new palliative therapeutic approaches, like brachytherapy, the use
      of modern chemotherapeuticals, COX-2 and receptor-tyrosine kinase inhibitors,
      perhaps also in combination with PDT, has to be further investigated.

PMID- 15871066
TI  - Training in GI endoscopy: can we objectively predict the performance of trainees?
      A prospective correlation study.
AB  - BACKGROUND: No objective criteria have hitherto been available for assessing the
      individual talents and skills of trainees involved in GI endoscopy. The aim of
      our study was to compare the correlation of various psychological, psychomotor
      and cognitive tests (psy-tests) and of the subjective assessment of the trainer
      (expert assessment) at the beginning of the training with the objective
      performance of the trainees at the end of a one-week training period in upper GI
      endoscopy. METHODS: In a prospective study including 12 endoscopic centers, a
      total of 58 participants without any prior endoscopic experience were analyzed.
      During a practical training week in each center with the "Erlangen Endo-Trainer,"
      an assessment using a "score card" protocol was used as reference method. Prior
      to the start of the training, various psy-tests (personality test, vigilance
      endurance test, test of spatial thinking and two tests of sensorimotor
      coordination) as well as assessment of the trainer were obtained. These
      parameters were compared with a blinded analysis of the performance at the end of
      the training. RESULTS: There was significant overall improvement during the
      training course. Multiple logistic regression analysis revealed that testing
      sensorimotoric coordination was significantly associated with defined improvement
      margins (odds ratio 11.46, p = 0.035). An expert's judgment on the prognosis
      correlated also significantly with the trainee's improvement (OR = 41.46; p =
      0.018). Self-assessments were not significantly associated with performance or
      progress. CONCLUSIONS: Sensorimotoric tests may provide a reliable prediction of
      the trainee's learning progress. In contrast to self-assessment, the judgement of
      an experienced endoscopist provides the best guidance for the young candidate
      endoscopists prior to the start of his/her endoscopic training program.

PMID- 15871067
TI  - Acute fatty liver of pregnancy -- an underlying condition for herpes simplex type
      2 fulminant hepatitis necessitating liver transplantation.
AB  - The infrequent occurrence of herpes simplex virus (HSV) hepatitis in healthy
      women in comparison with the high prevalence of HSV infections suggests that, in
      addition to deranged immunity, an underlying condition in the liver might be
      necessary to develop HSV hepatitis. We report the case of a 28-year-old pregnant
      woman in the 28 (th) week of gestation. Following HSV type 2 infection of the
      uterine cervix, acute liver failure developed, necessitating urgent liver
      transplantation. In addition to fulminant HSV type 2 hepatitis, the explanted
      liver also showed the histological features of acute fatty liver of pregnancy.
      The presented case suggests a possible pathogenetic role of acute fatty liver of
      pregnancy in the development of fulminant HSV hepatitis following recurrent
      infection with HSV in healthy pregnant women. We believe that early
      histopathological diagnosis, followed by specific antiviral treatment and liver
      transplantation in selected patients may improve the clinical outcome of
      otherwise almost uniformly fatal HSV hepatitis.

PMID- 15871068
TI  - [A 67-year-old patient with diarrhoea and constipation without any pathological
      findings in virtual colonoscopy].
AB  - Virtual colonoscopy provides a computer-simulated endoluminal perspective of the
      air-filled, distended colon using modern CT scanning (spiral CT). According to
      recent studies the sensitivity and specificity of this technique are high for
      adenomatous polyps > or = 10 mm. A 67-year-old patient was admitted to our
      hospital because of diarrhoea and constipation, associated with abdominal pain in
      the lower right abdomen. Prior to admission the patient had undergone virtual
      colonoscopy in a specialised radiological practice which had detected no
      abnormalities apart from colonic diverticulosis. However, conventional video
      colonoscopy revealed a subtotal circular malignant stenosis in the region of the
      right colonic flexure. A poorly differentiated adenocarcinoma was diagnosed
      histologically. Staging showed peritoneal carcinosis with infiltration of the
      right ureter and lymphangiosis carcinomatosa of the pectoral lobe of the left
      lung. After right hemicolectomy because of metastasised carcinoma of the
      ascending colon (pT4pN1pM1) we started palliative chemotherapy with oxaliplatin,
      5-fluorouracil and leucovorin. The risk of misdiagnosis by virtual colonoscopy is
      clearly increased in patients with subtotal tumour stenosis of the ascending
      colon. Conventional video-colonoscopy remains the gold standard for the diagnosis
      of colorectal carcinoma.

PMID- 15871069
TI  - [Diagnosis and treatment of acute pancreatitis].
AB  - In patients with abdominal pain, an acute pancreatitis is likely when lipase is
      elevated more than 3-fold above normal. The diagnosis should be confirmed by an
      imaging technique (either sonography or CT). The determination of the severity is
      difficult as all methods (laboratory values, imaging systems, scores) exhibit a
      significant uncertainty. The regular clinical investigation of the patients is
      still needed. In contrast to a severe course, in mild or moderate disease the
      treatment of the patient in an intensive care unit is not obligatory. In biliary
      pancreatitis the extraction of biliary stones after papillotomy is indicated and
      in severe disease the procedure should be done without delay. Meanwhile enteral
      nutrition is standard treatment although the data are not completely convincing.
      Further measures are administration of pain killers, volume substitution and
      treatment of pulmonary and renal failure. Although data are not completely clear
      the prophylactic administration of antibiotics in necrotizing pancreatitis is
      routine. Puncture of the necrosis may be used to detect the responsible
      microorganisms. In patients with infected necrosis who deteriorate during
      conservative treatment, necrosectomy may be an option. There is a tendency to
      postpone the operation until the necrosis can be clearly separated from non
      necrotic tissue. Although a specific pharmacological agent for the treatment of
      pancreatitis is still not available, the above procedure has led to a significant
      reduction of mortality in patients with severe acute pancreatitis.

PMID- 15871070
TI  - [Probiotics as therapeutic agents in irritable bowel syndrome].
AB  - Probiotics are defined as living micro-organisms which, when administered in
      large amounts, confer a health benefit on the host. The use of probiotics in the
      therapy of infectious bowel diseases as well as maintaining remission of
      ulcerative colitis and in pouchitis is evidence-based. Also, in several studies
      proof could be supplied that specific probiotics relieve the symptoms and the
      course of irritable bowel syndrome. Some trials showed a significant improvement
      of irritable bowel syndrome-related constipation via Lactobacillus casei Shirota
      and E. coli Nissle 1917. Lactobacillus plantarum has been proven effective in
      reducing pain and abdominal bloating. However, in most of the studies rather
      small numbers of patients were examined. Furthermore, these studies do not always
      closely follow scientific standards (randomised, double-blind, placebo
      controlled). Therefore, confirmatory studies are necessary to examine the effect
      of probiotics in irritable bowel syndrome.

PMID- 15871071
TI  - [Current diagnostics and therapy for carcinomas of the biliary tree and
      gallbladder].

PMID- 15871076
TI  - [Clinical highfield MR].
AB  - MRI-imaging using a field strength above 2 Tesla -- recently termed "highfield
      MRI" -- has come into clinical use in the last three years. For technical
      reasons, the initial application of highfield MRI concentrated on examinations of
      the brain. By improving the technology and solving specific problems, it has now
      become possible to perform total body scans. Only a few studies have been carried
      out to determine whether the use of highfield MRI is advantageous compared to
      scanning at the usual field strengths, and what these advantages might be. MR
      angiography of cerebral vessels as well as certain aspects of structural imaging
      of the brain seem to benefit. BOLD contrast fMRI, perfusion analysis and
      spectroscopy all seem to improve. For total body scanning, it is already possible
      to examine certain areas in "1.5 Tesla quality", in some cases shortening
      scanning time considerably. This survey summarises the present state of
      knowledge, realising that the presentation might not be all-comprising since
      progress in this field is very dynamic.

PMID- 15871077
TI  - New optional IVC filter for percutaneous retrieval--in vitro evaluation of
      embolus capturing efficiency.
AB  - PURPOSE: In-vitro evaluation of a new caval filter (Cook Celect Filter) developed
      for delayed percutaneous retrieval in comparison to the Gunther Tulip filter.
      MATERIALS AND METHODS: The new Celect filter is constructed on the basis of the
      Tulip filter and consists of 4 primary anchoring legs and additional 8 thinner
      secondary wires to stabilize the filter and to guarantee adequate filtering
      efficiency. The filtering wires are of the same amount and equal distribution as
      the filtering wires of the Tulip filter. The secondary wires are arranged in such
      a way that percutaneous filter retrieval should be possible even if the wires are
      incorporated into the caval wall. In a flow model (tube size o15-, o22- and o30
      mm), the filter was exposed to single and multiple emboli (blood clots) of
      different sizes (3 x 5, 3 x 10, 5 x 10, 3 x 20, 5 x 20, 7 x 10, 7 x 20 to 10 x 24
      mm) to analyse the embolus capturing efficiency under different conditions
      including eccentric and concentric, horizontal and vertical positions in
      comparison to the Tulip filter. All testing was carried out in SPSS analytic
      software; statistical significance was assumed for p-values < 0.05. RESULTS: The
      in-vitro embolus capturing efficiency of the Celect filter proved to be
      equivalent to the Tulip filter. In the single-embolus test, 91.6 % of the clots
      were captured by the Celect filter and 87.2 % by the Tulip filter (p = 0.042).
      Large clots ranging from 7 x 10 to 10 x 24 mm were captured in all cases, whereas
      the capture rates for the 3 x 5-mm and 3 x 10-mm clots were lower. The filters
      captured significantly more clots in the concentric than in the eccentric
      location. There was no significant difference between the overall capture rates
      of the two filters in the multi-clot test (72.2 % vs. 75.1 %), which showed
      deterioration of filter function during multiple clot exposure. With the 15-mm
      tube, the Celect filter had a significantly higher capture rate than the Tulip
      filter, whereas it was lower with the o30-mm tube. There was no significant
      difference between the filters in a o22-mm tube. The pressure gradient across the
      filters when exposed to blood clots ranged from 4.9 - 7.4 mm Hg for the Celect
      filter and 5.7 - 6.8 mm Hg for the Tulip filter in the single-embolus testing.
      There was no significant difference in the multi-clot tests. CONCLUSION: The new
      Celect filter showed similar in-vitro capture properties as the Gunther Tulip
      filter and deserves further in-vivo testing.

PMID- 15871078
TI  - [Contribution of early systole to total antegrade flow volume in breath-hold
      phase-contrast flow measurements].
AB  - PURPOSE: To evaluate the contribution of early systole for the assessment of
      antegrade aortic flow volume by breath-hold velocity-encoded magnetic resonance
      (MR) flow measurements. MATERIALS AND METHODS: Expiratory breath-hold fast low
      angle shot (FLASH) phase-contrast flow measurements (temporal resolution tRes 61
      msec, shared phases) perpendicular to the proximal ascending aorta and short axis
      true fast imaging with steady-state precession (TrueFISP) cine MR ventriculometry
      (tRes 34.5 msec) were performed in ten healthy male volunteers on a 1.5 T MR
      system (Sonata, Siemens Medical Solutions). Antegrade aortic flow volume (AFV)
      and left ventricular stroke volume (LV-SV) were evaluated using Argus Ventricular
      Function and Argus Flow Software, version MR 2002B (Siemens Medical Solutions). A
      beta release of Argus Flow MR 2004A allowed interpolation of the flow up-slope
      during early systole to the preceding R-wave trigger. The respective
      intraindividual median differences between the AFV of each flow evaluation and LV
      SV as well as between both AFV measurements were calculated and compared using
      the sign test for paired samples. RESULTS: Non-interpolated AFV significantly
      deviated from LV-SV (p = 0.006), underestimating the latter by 13.1 mL (13 %).
      Interpolating aortic flow during early systole significantly increased AFV by
      10.8 mL (13 %) compared to the flow evaluation which did not take early systole
      into account (p = 0.006). AFV with interpolation of early systolic flow agreed
      well with LV-SV (median difference - 3.0 mL or - 3 %, respectively), and no
      significant difference between these measurements was found (p = 1.0).
      CONCLUSION: Flow during early systole contributes substantially to total forward
      flow volume in the ascending aorta. Interpolation of the early systolic up-slope
      is therefore recommended for the evaluation of breath-hold phase-contrast flow
      measurements.

PMID- 15871079
TI  - [Systematic analysis of the geometry of a defined contrast medium bolus-
      implications for contrast enhanced 3D MR-angiography of thoracic vessels].
AB  - PURPOSE: Little is known about the dispersion of a defined contrast bolus during
      its passage through the heart and pulmonary vasculature. The purpose of this
      study was to analyze factors influencing a defined contrast bolus for ce-MRA of
      thoracic vessels. MATERIALS AND METHODS: For analysis of bolus geometry, an ECG
      gated saturation-recovery Turbo-Flash sequence with a TI of 20 msec was used. It
      was acquired axially at the level of the pulmonary trunc, so that with one data
      acquisition a curve analysis was possible in the ascending and descending aorta,
      and in the pulmonary trunc. Twenty-nine patients received 3 ml of Gd-DTPA diluted
      with saline to a total of 20 ml. Contrast injection was done using a MR
      compatible power injector with injection rates varying between 1, 2 and 4 ml/sec.
      Each injection was followed by a saline flush of 20 ml with the same injection
      rate and mode. Cardiac function was assessed by cine imaging, and phase contrast
      measurements. After normalization to baseline signal intensity (SI), bolus curves
      were fitted using a gamma-variate fit and peak signal intensity (peak SI), time
      to-peak (TP), upslope, mean transit time (MTT) and dispersion of the contrast
      bolus were calculated. Furthermore, T (1) and [Gd] in the experimental setting
      were calculated as follows: T (1) = T (1 o)/ ln [SI/SI (0)], and [Gd] (exp) =
      [1/T (1) - 1/T (1 o)]/ R (1.) They were then extrapolated [Gd] to clinical
      conditions by [Gd] (clin) = [Gd] (exp) . 10/1.5, and minimal blood T (1) by T
      (1)(clin) = 1 / [1/T (1 o) + R (1) [Gd] (clin)]. RESULTS: With increasing
      injection rate, there was a significant decrease (p < 0.001) of MTT in all target
      vessels. However, this decrease was not linear: a 4-fold increase in injection
      rate lead to a 2-fold decrease in MTT e. g. in the ascending aorta. MTT was
      significantly shorter in the pulmonary trunc compared with that in the ascending
      and descending aorta (p < 0.001), regardless of injection rate (p < 0.001). Vice
      versa, dispersion of the contrast bolus was significantly lower in the pulmonary
      trunc, and increased with higher injection rates. There was no clinically
      relevant difference in minimal blood T (1) between the different target vessels,
      for clinical conditions extrapolated values ranged between 20 und 79 msec. Heart
      function parameters only had a minor influence of bolus curve parameters.
      CONCLUSION: Analysis of bolus geometry enables determination of transit times of
      a defined contrast bolus through a defined target vessel in the thoracic cavity.
      Bolus geometry is mainly determined by injection parameters, cardiac function is
      of minor importance. Dispersion of contrast bolus and MTT increase from the
      pulmonary trunc to the ascending aorta. The knowledge of these facts may help
      optimizing of injection parameters and the total amount of contrast agent for
      contrast-enhanced MRA of thoracic vessels.

PMID- 15871080
TI  - [Does HRCT-emphysema index represent the entire lung?].
AB  - PURPOSE: : Comparison of emphysema index derived of thin section MD-CT of the
      entire lung volume and HRCT, simulated by calculation of every twentieth image of
      the whole data-set. MATERIALS AND METHODS: Pulmonary emphysema was quantified by
      semiautomatic, segmentation of lung borders and assessment of lung volume and
      emphysema volume within these borders. The emphysema index (pixel index) was
      calculated. Statistical analysis was done by the sign-test and Bland-Altman
      analysis. RESULTS: Median lung volume, emphysema volume and emphysema index are
      significantly higher in simulated HRCT. Median lung volume (emphysema volume)
      calculated by HRCT is 5118 ml (407 ml) and 5040 ml (367 ml) calculated by the
      entire MD-CT data-set, representing differences of 1 and 8 % related to the
      median lung and emphysema volumes. Emphysema index is 0.09 (HRCT) and 0.08 (MD
      CT). CONCLUSION: HRCT overrates emphysema index compared to thin section MD-CT of
      the entire lung volume.

PMID- 15871081
TI  - [Functional imaging of the lung using a gaseous contrast agent: (3)helium
      magnetic resonance imaging].
AB  - Current imaging methods of the lung concentrate on morphology as well as on the
      depiction of the pulmonary parenchyma. The need of an advanced and more subtle
      imaging technology compared to conventional radiography is met by computed
      topography as the method of choice. Nevertheless, computed tomography yields very
      limited functional information. This is to be derived from arterial blood gas
      analysis, spirometry and body plethysmography. These methods, however, lack the
      scope for regional allocation of any pathology. Magnetic resonance imaging of the
      lung has been advanced by the use of hyperpolarised (3)Helium as an inhaled
      gaseous contrast agent. The inhalation of the gas provides functional data by
      distribution, diffusion and relaxation of its hyperpolarised state. Because
      anatomical landmarks of the lung can be visualised as well, functional
      information can be linked with regional information. Furthermore, the method
      provides high spatial and temporal resolution and lacks the potential side
      effects of ionising radiation. Four different modalities have been established:
      1. Spin density imaging studies the distribution of gas, normally after a single
      inhalation of contrast gas in inspiratory breath hold. 2. Dynamic cine imaging
      studies the distribution of gas with respect to regional time constants of
      pulmonary gas inflow. 3. Diffusion weighted imaging can exhibit the presence and
      severity of pulmonary airspace enlargement, as in pulmonary emphysema. 4. Oxygen
      sensitive imaging displays intrapulmonary oxygen partial pressure and its
      distribution. Currently, the method is limited by comparably high costs and
      limited availability. As there have been recent developments which might bring
      this modality closer to clinical use, this review article will comprise the
      methodology as well as the current state of the art and standard of knowledge of
      magnetic resonance imaging of the lung using hyperpolarised (3)Helium.

PMID- 15871082
TI  - [Iliofemoral and iliocaval interventions in deep venous thrombosis].
AB  - Significant spontaneous thrombus disintegration in deep venous thrombosis (DVT)
      occurs very infrequently. On the contrary, these thrombi are prone to
      appositional growth and migration into the pulmonary arteries. The development of
      chronic venous insufficiency due to postthrombotic syndrome is a frequent
      consequence of DVT. Therapeutic options in DVT include anticoagulation and
      recanalising procedures such as thrombolysis and thrombectomy. After appropriate
      indication assessment, the interventional radiologist can offer an efficacy
      proven minimally-invasive vessel restitution approach by performing locoregional
      thrombolysis, pharmacomechanical therapy or, particularly in iliocaval
      thrombosis, mechanical thrombectomy. These methods not only serve to restitute of
      vessel patency, but also allow preserving venous valve function. In DVT with
      recurrent pulmonary embolism, retrievable filters with extended implantation
      duration can be deployed. In chronic proximal venous flow obstruction or in case
      of significant residual stenosis after thrombolysis, balloon angioplasty with
      stent implantation is the treatment modality of choice. Consequently, the
      radiologist can adopt an important role in the treatment of extensive venous
      disease. In this article, the treatment modalities concerning iliofemoral and
      iliocaval thrombosis are demonstrated and illustrated.

PMID- 15871083
TI  - [TACE: therapy of the HCC before liver transplantation--experiences].
AB  - PURPOSE: Analysis of the course of disease in patients with histologically proven
      HCC before and after orthotopic liver transplantation (LTx) who received
      transarterial chemoembolization (TACE). MATERIAL AND METHODS: Thirty-five of a
      total collective of 363 patients with histologically proven HCC underwent LTx.
      Before LTx, all patients were treated with sequential TACE. According to
      treatment pattern, TACE should be performed every 6 weeks, using a suspension
      consisting of max. 10 mg Mitomycin C as well as 10 - 30 ml iodized oil
      (Lipiodol). Patients were classified according to the Milano criteria. Criteria
      were called exceeded if the tumor size was > 5 cm and/or > 3 tumors larger than 3
      cm were found. Therapy success and liver function were examined by means of
      spiral CT and laboratory controls. Investigation parameters included the number
      of tumor knots as well as the maximum tumor size. Additionally, the Lipiodol
      accumulation, the patency of the portal vein and the occurrence of complications
      were checked. RESULTS: Altogether, 184 TACE procedures were accomplished (5.3 +/-
      3.3, range 1 - 14). The waiting period up to the transplantation amounted to 366
      +/- 255 days (range 44 - 1137). The average number of tumor knots for each
      patient was 3.1 +/- 2.2 before and 2.9 +/- 2.2 after TACE (p = 0.887). The
      average tumor size was 4.2 +/- 2.5 before and 2.8 +/- 1.4 after TACE. The Milano
      criteria to LTx crossed 17/35 patients. Patients with exceeded Milan criteria
      showed a highly significant size reduction of the tumor after TACE (p = 0.001);
      in 9/17 cases the transplantation criteria were secondarily fulfilled through
      downstaging. A successful LTx was accomplished in 35/35 cases. Follow up after
      LTx was 769 +/- 509 days. The tumor recurrence in patients with exceeded vs.
      fulfilled transplantation criteria was 11.1 % vs. 11.8 % (p = 0.99). The
      recurrence free survival was 93.3 %, 82.5 % and 82.5 % at 1, 3 and 5 years,
      respectively. There were no relevant differences between patients with exceeded
      vs. fulfilled transplantation criteria (p = 0.99). CONCLUSION: The sequential
      TACE is an effective method for the therapy of the HCC before LTx in selected
      patients. A relevant downsizing could be achieved by TACE in patients with
      advanced HCC. Patients with larger tumors showed a significantly stronger size
      reduction after TACE. The recurrence rate and the survival rate for patients with
      advanced or small tumors do not differ.

PMID- 15871084
TI  - [Teleradiology according to the x-ray ordinance--exemplary application of the
      open source software SecTelMed].
AB  - PURPOSE: Establishing a teleradiology connection according to the
      Rontgenverordnung (RoV) between a peripheral hospital and a university clinic
      will contribute to improve the radiological emergency treatment on weekends,
      holidays and at night. It will also better the medical care for patients and help
      to lower the costs. MATERIALS AND METHODS: By using the open source software
      SecTelMed, the radiological picture is transferred via an internet-linked SSH
      communication server. The integration of the teleradiological data transfer into
      the actual workflow is attained by using the already existing PACS
      infrastructure. While its installation is still under construction, it is
      actually employed for transferring a patient's preliminary investigations and
      obtaining second opinions. RESULTS: The project proves a reliable and affordable
      teleradiology according with RoV by using open source software. The applied
      infrastructure ensures an unproblematical teleradiological treatment as well as a
      safe picture transfer for medical consulting (second opinion) even for large CT
      examinations of 1,000 pictures and more. CONCLUSION: The implementation of the
      technical requirements on teleradiology according with the Rontgenverordnung can
      be reliably attained by applying the open source software SecTelMed.

PMID- 15871085
TI  - [Teleradiology with DICOM e-mail: recommendations of @GIT].
AB  - E-mail is ideal for ad-hoc connections in teleradiology. The DICOM standard
      offers the possibility to append DICOM data types as a MIME attachment to any e
      mail, thus ensuring the transmission of the original DICOM data. Nevertheless,
      there are additional requirements (e.g. protection of data privacy) which must be
      obeyed. Because of the lack of given standards which would grant interoperability
      as well as manufacturer independence, teleradiology has not been established in
      Germany until today. Therefore, the IT-Team (Arbeitsgemeinschaft fur
      Informationstechnologie, @GIT) of the Radiological Society of Germany (Deutsche
      Rontgengesellschaft, DRG) set up an initiative to standardise telemedicine by
      using e-mail. Its members agreed that an e-mail-based variant would be the most
      practicable way to a communication solution -- as easy to implement as to use. In
      their opinion, e-mail represents the smallest common denominator for a safe data
      interchange that would fulfill the legal advantages for telemedicine in Germany.

PMID- 15871086
TI  - [Self-organizing neural networks for automatic detection and classification of
      contrast (media) enhancement of lesions in dynamic MR-mammography].
AB  - PURPOSE: Investigation and statistical evaluation of "Self-Organizing Maps," a
      special type of neural networks in the field of artificial intelligence,
      classifying contrast enhancing lesions in dynamic MR-mammography. MATERIAL AND
      METHODS: 176 investigations with proven histology after core biopsy or operation
      were randomly divided into two groups. Several Self-Organizing Maps were trained
      by investigations of the first group to detect and classify contrast enhancing
      lesions in dynamic MR-mammography. Each single pixel's signal/time curve of all
      patients within the second group was analyzed by the Self-Organizing Maps. The
      likelihood of malignancy was visualized by color overlays on the MR-images. At
      last assessment of contrast-enhancing lesions by each different network was rated
      visually and evaluated statistically. RESULTS: A well balanced neural network
      achieved a sensitivity of 90.5 % and a specificity of 72.2 % in predicting
      malignancy of 88 enhancing lesions. Detailed analysis of false-positive results
      revealed that every second fibroadenoma showed a "typical malignant" signal/time
      curve without any chance to differentiate between fibroadenomas and malignant
      tissue regarding contrast enhancement alone; but this special group of lesions
      was represented by a well-defined area of the Self-Organizing Map. DISCUSSION:
      Self-Organizing Maps are capable of classifying a dynamic signal/time curve as
      "typical benign" or "typical malignant." Therefore, they can be used as second
      opinion. In view of the now known localization of fibroadenomas enhancing like
      malignant tumors at the Self-Organizing Map, these lesions could be passed to
      further analysis by additional post-processing elements (e.g., based on T2
      weighted series or morphology analysis) in the future.

PMID- 15871087
TI  - [MR-based methods of the functional imaging of the central nervous system].
AB  - This review presents the basic principles of functional imaging of the central
      nervous system utilizing magnetic resonance imaging. The focus is set on
      visualization of different functional aspects of the brain and related
      pathologies. Additionally, clinical cases are presented to illustrate the
      applications of functional imaging techniques in the clinical setting. The
      relevant physics and physiology of contrast-enhanced and non-contrast-enhanced
      methods are discussed. The two main functional MR techniques requiring contrast
      enhancement are dynamic T1- and T2*-MRI to image perfusion. Based on different
      pharmacokinetic models of contrast enhancement diagnostic applications for
      neurology and radio-oncology are discussed. The functional non-contrast enhanced
      imaging techniques are based on "blood oxygenation level dependent (BOLD)-fMRI
      and arterial spin labeling (ASL) technique. They have gained clinical impact
      particularly in the fields of psychiatry and neurosurgery.

PMID- 15871088
TI  - [Magnetic resonance imaging of the brain in patients with cardiac pacemakers.
      Experimental and clinical investigations at 1.5 Tesla].
AB  - PURPOSE: In-vitro and In-vivo evaluation of feasibility and safety of MRI of the
      brain at 1.5 T in patients with implanted pacemakers (PM). MATERIALS AND METHODS:
      24 PM models and 45 PM electrodes were tested In-vitro with respect to
      translational forces, heating of PM leads, behaviour of reed switch (activated
      vs. deactivated) and function at a 1.5 T MRI-system (actively shielded, maximum
      field gradient: 30 mT/m; rise time: 150 T/m/s). Based on these results, 63 MRI
      examinations in 45 patients with implanted PM were performed. Prior to MRI the PM
      were re-programmed in an asynchronous mode. The maximum SAR of MRI-sequences was
      limited to 1.2 W/kg. Continuous monitoring of ECG and pulse oximetry was
      performed during MRI. PM inquiry was performed prior to MRI, immediately after
      MRI and -- to assess long-term damages -- three months after the MRI exams,
      including determination of stimulation thresholds to assess potential thermal
      myocardial injuries at the lead tips. RESULTS: Translational forces (F (max) < or
      = 560 mN) and temperature increase (DeltaT (max) < or = 2.98 degrees C) were in a
      range which does not represent a safety concern from a biophysical point of view.
      No changes to the programmed parameters of the PM or damage of PM components were
      observed neither In-vitro (n = 0/24) nor In-vivo (n = 0/63). Despite the strong
      magnetic field, the reed switch remained deactivated in 54 % (13/24) of the cases
      during In-vitro simulated MRI exams of the brain. All patient studies (n = 63/63)
      could be completed without any complications. Atrial and ventricular stimulation
      thresholds (expressed as pulse duration at 2-fold rheobase) did not change
      significantly immediately post-MRI nor in the 3 months follow-up (pre-MRI: 0.17
      ms +/- 0.13 ms, post-MRI: 0.18 ms +/- 0.14 ms, 3 months follow-up: 0.17 ms +/-
      0.12 ms). CONCLUSION: MRI of the brain at 1.5 Tesla can be safely performed in
      carefully selected clinical circumstances when appropriate strategies are used
      (re-programming the PM to an asynchronous mode, continuous monitoring of ECG and
      pulse oximetry, limiting the SAR value of the MRI sequences, cardiological stand
      by). Based on these studies, implanted PM should not longer be regarded as an
      absolute contraindication for MRI at 1.5 T.

PMID- 15871090
TI  - [Analysis of the static pressure volume curve of the lung in experimentally
      induced pulmonary damage by CT-densitometry].
AB  - PURPOSE: To study quantitative changes of lung density distributions when
      recording in- and expiratory static pressure-volume curves by single slice
      computed tomography (CT). MATERIALS AND METHODS: Static in- and expiratory
      pressure volume curves (0 to 1000 ml, increments of 100 ml) were obtained in
      random order in 10 pigs after induction of lung damage by saline lavage.
      Simultaneously, CT acquisitions (slice thickness 1 mm, temporal increment 2 s)
      were performed in a single slice (3 cm below the carina). In each CT image lung
      segmentation and planimetry of defined density ranges were achieved. The lung
      density ranges were defined as: hyperinflated (-1024 to -910 HU), normal aerated
      (-910 to -600 HU), poorly aerated (-600 to -300 HU), and non aerated (-300 to 200
      HU) lung. Fractional areas of defined density ranges in percentage of total lung
      area were compared to recorded volume increments and airway pressures
      (atmospheric pressure, lower inflection point (LIP), LIP*0.5, LIP*1.5, peak
      airway pressure) of in- and expiratory pressure-volume curves. RESULTS:
      Quantitative analysis of defined density ranges showed no differences between in-
      and expiratory pressure-volume curves. The amount of poorly aerated lung
      decreased and normal aerated lung increased constantly when airway pressure and
      volume were increased during inspiratory pressure-volume curves and vice versa
      during expiratory pressure-volume loops. CONCLUSION: Recruitment and
      derecruitment of lung atelectasis during registration of static in- and
      expiratory pressure-volume loops occurred constantly, but not in a stepwise
      manner. CT was shown to be an appropriate method to analyse these recruitment
      process.

PMID- 15871089
TI  - [Estimation of diffuse bone marrow infiltration of the spine in multiple myeloma:
      correlation of MRT with histological results].
AB  - PURPOSE: To determine the detection of diffuse bone marrow infiltration with MRI
      in comparison with histopathological findings. MATERIALS AND METHODS: MRI was
      performed on 45 patients with histologically proven multiple myeloma and on 30
      healthy individuals. Three experienced radiologists read separately Tl-weighted
      SE sequences, STIR sequences and the combination of Tl-weighted SE and STIR
      sequences of the spine. Additionally, Tl-weighted SE sequences were obtained
      after gadolinium administration and the percentage increase in signal intensity
      was calculated. Bone marrow histology was used as gold standard for assessing the
      grade of infiltration. A dichotomous decision (infiltration yes/no) was made when
      assessing the MRI examinations. RESULTS: For the visual detection of diffuse
      infiltration, the best sensitivity was found with Tl-weighted SE sequences,
      achieving 71 % on average. The specificity was 89 %. The STIR sequences showed a
      sensitivity of 61 % and a specificity of 98 %, and the combination of Tl
      weighted/STIR-sequences achieved a sensitivity of 65 % and a specificity of 94 %.
      In comparison with the histological findings, the sensitivity of the Tl-weighted
      sequences was 35 % for low-grade, 89 % for moderate and 100 % for high-grade
      infiltration. The application of contrast material with calculation of the
      percentage signal increase improved the detection by 7 %. CONCLUSION: The
      sensitivity of the visual detection of diffuse multiple myeloma with unenhanced
      MRI is limited for low-grade or moderate infiltration, whereas the sensitivity
      for high grade infiltration is reliable. The specificity is high and the
      diagnostic confidence improves after application of contrast material with
      calculation of the percentage increase in signal intensity.

PMID- 15871091
TI  - [Pneumatosis intestinalis coli--a rare find in CT-colonoscopy].

PMID- 15871092
TI  - [Pneumatosis intestinalis coli].

PMID- 15871093
TI  - [Spinal dura fistula].

PMID- 15871108
TI  - Human papillomavirus through the ages.

PMID- 15871109
TI  - Nasopharyngeal carriage of pneumococcal pediatric serotypes: a risk for acute and
      recurrent otitis media in children and for invasive disease in susceptible
      adults.

PMID- 15871110
TI  - Prospects for improving African trypanosomiasis chemotherapy.

PMID- 15871111
TI  - Epidemiologic profile of type-specific human papillomavirus infection and
      cervical neoplasia in Guanacaste, Costa Rica.
AB  - BACKGROUND: Detailed epidemiologic studies of cervical type-specific human
      papillomavirus (HPV) infection in large populations are scarce. METHODS: We
      recruited a population-based cohort in Guanacaste, Costa Rica. Participants were
      interviewed, screened for cervical neoplasia, and tested for >40 HPV types by use
      of MY09/11 L1 consensus primer polymerase chain reaction. We estimated the risk
      factors for infection and the associations between type-specific HPV infections
      and cervical intraepithelial neoplasia (CIN) and cancer in 8514 sexually active
      women who had not undergone a hysterectomy. RESULTS: The overall HPV prevalence
      was 26.5%. The most common type was HPV-16 (3.6% of the population). HPV
      prevalence showed a U-shaped age-specific curve. Sexual behaviors were the main
      determinants of oncogenic and nononcogenic infections; age at first sexual
      intercourse was not independently associated with infection. Barrier
      contraceptive use was somewhat protective against infection. Oncogenic infections
      were strongly associated with risk of all grades of CIN and of cancer. Types 16,
      18, and 58 were the most common in women diagnosed with CIN3 and cancer. Except
      for those that included HPV-16, multiple-type infections were associated with an
      increased risk (compared with that for single-type infections) of all grades of
      CIN and of cancer. CONCLUSIONS: We confirmed the bimodal age pattern of HPV
      infection in Guanacaste and the sexually transmitted nature of both oncogenic and
      nononcogenic HPV types.

PMID- 15871112
TI  - A prospective study of age trends in cervical human papillomavirus acquisition
      and persistence in Guanacaste, Costa Rica.
AB  - BACKGROUND: Cross-sectional human papillomavirus (HPV) DNA prevalence peaks at
      young ages, reflecting sexual acquisition and typically rapid clearance. In some
      populations, HPV prevalence demonstrates a second peak in older women.
      Longitudinal data may help to explain this second peak. METHODS: We followed a
      population-based cohort of 7237 women in Guanacaste, Costa Rica, in which we had
      previously observed a second peak in the baseline HPV prevalence in older women.
      We tested for >40 HPV types by polymerase chain reaction. We analyzed age
      specific patterns of acquisition and persistence 5-7 years after enrollment for
      individual HPV types. RESULTS: At enrollment and follow-up, cross-sectional data
      revealed U-shaped age-specific HPV prevalence curves for virtually every type,
      with higher prevalences in the younger and older women than in the middle-aged
      women. Prospectively, acquisition of types decreased significantly as women aged
      (PTrend<.05, for both), with the highest peak in young women and a secondary
      minor peak in older women. Type-specific persistence of HPV increased with age
      (PTrend<.0001). Overall, HPV acquisition predominated at younger ages, whereas
      persistent infections gradually became more prominent with age (PTrend<.0001).
      CONCLUSIONS: Newly apparent infections decreased, whereas persistence increased,
      with age; this latter tendency supports the utility of HPV screening in older
      women.

PMID- 15871113
TI  - Seroprevalence of human papillomavirus type 16 in children.
AB  - We evaluated the prevalence of antibodies to human papillomavirus (HPV) type 16
      in a representative sample of children 6-11 years of age in the United States.
      Serum samples and questionnaire data were collected between 1991 and 1994, for
      the National Health and Nutrition Examination Survey III. HPV-16-specific
      immunoglobulin G antibodies were detected by an HPV-16 L1 virus-like particle
      based enzyme-linked immunosorbant assay. Overall, 2.4% of 1316 children 6-11
      years of age were seropositive. Seroprevalence was higher in boys than in girls
      (3.5% vs. 1.2%; P=.08) and in children >7 years of age than in children < or =7
      years of age (3.3% vs. 0.4%; P<.05). None of the variables tested for, including
      race/ethnicity, socioeconomic status, and urban or rural residence, were
      significantly associated with HPV-16 seropositivity. To explain HPV-16
      seropositivity in this population, further study is required.

PMID- 15871114
TI  - Clinical and laboratory manifestations of Sindbis virus infection: prospective
      study, Finland, 2002-2003.
AB  - Sindbis virus (SINV) is widespread in Europe, Africa, Australia, and Asia, but
      clinical infection occurs as epidemics in a few geographically restricted areas.
      We recently proved, by virus isolation from patients, that SINV is the causative
      agent of Pogosta disease, a mosquito-borne rash-arthritis occurring as larger
      epidemics every seventh year in Finland. Altogether, 86 patients with
      serologically verified SINV infection were recruited to the present study during
      the 2002 outbreak. We now describe in detail the duration, incidence, and
      characteristics of different symptoms; hematological parameters; antibody
      kinetics; and presence of SINV in different tissue samples. SINV RNA detection or
      virus isolation from blood and/or skin lesions was successful in 8 patients.
      Immunoglobulin (Ig) M antibodies became detectable within the first 8 days of
      illness, and IgG antibodies became detectable within the first 11 days of
      illness. During the acute phase of Pogosta disease, the typical symptoms were
      arthritis, itching rash, fatigue, mild fever, headache, and muscle pain. The most
      notable finding was that, in 50% of the patients, joint symptoms lasted for >12
      months.

PMID- 15871115
TI  - Human T lymphotropic virus type I (HTLV-I) proviral load in cerebrospinal fluid:
      a new criterion for the diagnosis of HTLV-I-associated myelopathy/tropical
      spastic paraparesis?
AB  - Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) is associated with accumulation of HTLV-I-infected T cells
      in the central nervous system (CNS). However, data on HTLV-I proviral load in the
      CNS at the asymptomatic stage are still lacking. We measured HTLV-I proviral load
      in cerebrospinal fluid (CSF) cells from 17 patients with HAM/TSP and 25
      asymptomatic carriers. The percentage of HTLV-I-infected cells in CSF cells and
      the CSF cell : peripheral blood mononuclear cell HTLV-I proviral load ratio were
      always >10% and >1, respectively, in the patients with HAM/TSP but were always
      <10% and <1, respectively, in the asymptomatic carriers. We propose that
      determination of HTLV-I proviral load in CSF cells should be included as a new
      parameter for the diagnosis of HAM/TSP.

PMID- 15871116
TI  - Hepatitis B immunity in United States military recruits.
AB  - BACKGROUND: In 2002, the US Department of Defense (DoD) mandated hepatitis B
      immunization for military recruits. A DoD study reported that screening for
      immunity with selective immunization would be cost-effective at a prevalence of
      immunity of >12%. The prevalence of hepatitis B immunity in the military recruit
      population was unknown. METHODS: We studied a random sample of Army, Navy, and
      Marine Corps new recruits (2400 men and women from all 50 states, Puerto Rico,
      and US territories). Banked serum samples collected in 2001 were tested for
      antibody to hepatitis B surface antigen (anti-HBs) by AUSAB enzyme-linked
      immunoassay (EIA). Results were evaluated by military service branch, age, sex,
      race, level of education, geographic region of origin, and presence of state
      immunization laws. RESULTS: The overall prevalence of anti-HBs seropositivity,
      adjusted to the age distribution of the recruit population in 2001, was 31.5%
      (95% confidence interval [CI], 29.6%-33.4%). The prevalence of anti-HBs
      seropositivity, directly adjusted to the 18-35-year-old US population in 2000,
      was 23.0% (95% CI, 20.7%-25.3%). Anti-HBs seropositivity prevalence was highest
      among the young, decreased with increasing age, and was higher in women, recruits
      from the Northeast and West, and recruits from states with laws mandating
      hepatitis B immunization before entry into elementary and middle school.
      CONCLUSIONS: Screening new recruits for evidence of immunity before hepatitis B
      immunization is indicated. The prevalence of immunity increased with successive
      birth cohorts and may reflect the success of childhood immunization programs.

PMID- 15871117
TI  - Virus-specific cytotoxic T lymphocytes differentially express cell-surface
      leukocyte immunoglobulin-like receptor-1, an inhibitory receptor for class I
      major histocompatibility complex molecules.
AB  - Leukocyte immunoglobulin-like receptor-1 (LIR-1) is an inhibitory receptor that
      negatively regulates T cell effector functions after interaction with host class
      I major histocompatibility complex molecules and, additionally, binds to UL18, a
      human cytomegalovirus (HCMV)-encoded class I homologue. Here, we demonstrate that
      virus-specific cytotoxic T lymphocytes (CTLs) differentially express LIR-1, with
      high frequencies of expression on HCMV-specific CD8+ T cells and intermediate and
      low frequencies of expression on influenza virus-specific and Epstein-Barr virus
      (EBV)-specific CTLs, respectively. Expression of LIR-1 was dependent on CTL
      antigen specificity and was associated with a differentiated effector memory
      phenotype, as demonstrated by decreased expression of CD28 and increased
      expression of CD57. During primary HCMV and EBV infections, expression of LIR-1
      on virus-specific CTLs was low and increased slowly. These results indicate that
      expression of LIR-1 increases during differentiation of virus-specific CD8+
      effector T cells. Furthermore, they suggest that a potential immunoregulatory
      function of UL18 may be to preferentially target highly differentiated HCMV
      specific effector memory T cells during persistent infection.

PMID- 15871118
TI  - Neonatal measles immunity in rural Kenya: the influence of HIV and placental
      malaria infections on placental transfer of antibodies and levels of antibody in
      maternal and cord serum samples.
AB  - INTRODUCTION: Young infants are protected from measles infection by maternal
      measles antibodies. The level of these antibodies at birth depends on the level
      of antibodies in the mother and the extent of placental transfer. We investigated
      predictors of levels of measles antibodies in newborns in rural Kenya. METHODS: A
      total of 747 paired maternal-cord serum samples (91 from human immunodeficiency
      virus [HIV]-infected and 656 from HIV-uninfected mothers) were tested for measles
      immunoglobulin G antibodies. Placental malaria infection was determined by
      biopsy. Data on pregnancy history, gestational age, and anthropometric and
      socioeconomic status were collected. RESULTS: Infants born to HIV-infected
      mothers were more likely (odds ratio, 4.6 [95% confidence interval {CI}, 2.2
      9.7]) to be seronegative and had 35.1% (95% CI, 9.8%-53.2%) lower levels of
      measles antibodies than did those born to HIV-uninfected mothers. Preterm
      delivery, early maternal age, and ethnic group were also associated with reduced
      levels of measles antibodies. There was little evidence that placental malaria
      infection was associated with levels of measles antibodies in newborns.
      CONCLUSION: Our results suggest that maternal HIV infection may reduce levels of
      measles antibodies in newborns. Low levels of measles antibodies at birth render
      children susceptible to measles infection at an early age. This is of concern in
      sub-Saharan African countries, where not only is the prevalence of HIV high, but
      measles is the cause of much morbidity and mortality.

PMID- 15871119
TI  - Respiratory syncytial virus load predicts disease severity in previously healthy
      infants.
AB  - BACKGROUND: Elucidating the relationship between viral load and respiratory
      syncytial virus (RSV) disease severity is critical to understanding pathogenesis
      and predicting the utility of antivirals. METHODS: Previously healthy, naturally
      RSV-infected infants <24 months old not treated with ribavirin, passive antibody,
      or corticosteroids were prospectively studied (n=141). Viral loads were measured
      by fresh quantitative culture from nasal washes collected at a single time point
      shortly after hospitalization. RESULTS: The subjects' mean age was 112.1 days,
      and the mean estimated gestational age at birth was 38.38 weeks. RSV load
      decreased with longer durations of symptoms before specimen collection (P=.01).
      Male subjects had higher RSV loads than female subjects (P=.036). Significant
      independent predictors of longer hospitalization were congenital anomaly
      (P<.0001), lower weight on admission (P=.028), and higher nasal RSV load
      (P=.008). A 1-log higher RSV load predicted a 0.8-day longer hospitalization.
      Lower weight and higher RSV load were also independently associated with
      respiratory failure (P<.0005 and P=.0049, respectively) and requirement for
      intensive care (P=.0007 and P=.0048, respectively). CONCLUSIONS: In previously
      healthy infants, higher RSV loads measured at capturable time points after
      symptom onset predict clinically relevant measures of increased disease severity.

PMID- 15871120
TI  - Nasopharyngeal carriage of Streptococcus pneumoniae at the completion of
      successful antibiotic treatment of acute otitis media predisposes to early
      clinical recurrence.
AB  - OBJECTIVE: We sought to investigate the role of Streptococcus pneumoniae (SP)
      nasopharyngeal (NP) colonization after successful antibiotic treatment (Rx) of
      acute otitis media (AOM) in recurrent AOM (RAOM). PATIENTS AND METHODS: NP
      cultures were obtained from 494 (93%) of 530 patients at the end of antibiotic
      treatment (EOT). RESULTS: At enrollment, middle ear fluid (MEF) cultures in 418
      (79%) of 530 patients were positive for pathogens. At EOT, NP cultures in 208
      (42%) of 494 patients were positive for SP. RAOM was found in 130 (26%) of 494
      patients: 66 (32%) of 208 with SP-positive NP and 64 of 286 (22%) without SP
      positive NP at EOT (P=.026). MEF was positive for SP during RAOM in 34 (61%) of
      56 patients with SP-positive NP and 17 (36%) of 47 patients without SP-positive
      NP at EOT (P=.022). The same serotype was identified in 24 (80%) of 30 SP pairs;
      complete identity was found between isolates in 22 (96%) of 23 SP pairs.
      CONCLUSIONS: Early RAOM was more commonly caused by SP if the organism was
      present in NP at EOT during the initial AOM episode. Most SP-RAOM episodes were
      caused by SP isolates present in NP at EOT during the previous AOM episode.

PMID- 15871121
TI  - Effective treatment of experimental acute otitis media by application of volatile
      fluids into the ear canal.
AB  - Essential oils are volatile and can have good antimicrobial activity. We compared
      the effects of oil of basil (Ocimum basilicum) and essential oil components
      (thymol, carvacrol, and salicylaldehyde) to those of a placebo when placed in the
      ear canal of rats with experimental acute otitis media caused by pneumococci or
      Haemophilus influenzae. Progress was monitored by otomicroscopic examination and
      middle ear cultures. The treatment with oil of basil or essential oil components
      cured or healed 56%-81% of rats infected with H. influenzae and 6%-75% of rats
      infected with pneumococci, compared with 5.6%-6% of rats in the placebo group.
      Essential oils or their components placed in the ear canal can provide effective
      treatment of acute otitis media.

PMID- 15871122
TI  - Inhibition of Bacillus anthracis growth and virulence-gene expression by
      inhibitors of quorum-sensing.
AB  - Density-dependent gene expression, quorum sensing (QS), involves the synthesis
      and detection of low-molecular-weight molecules known as autoinducers. Inhibitors
      of bacterial QS systems offer potential treatment of infections with highly
      virulent or multidrug-resistant agents. We studied the effects on Bacillus
      anthracis growth and the virulence gene (pagA, lef, and cya) expression of the QS
      inhibitor (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone, which is
      naturally synthesized by the marine alga Delisea pulchra, as well as a related
      compound and synthetic derivatives. Growth of B. anthracis Sterne strain was
      substantially reduced in the presence of each furanone in a dose-dependent
      manner. When furanones were added to midlog-phase cultures of B. anthracis
      strains with LacZ reporters in pagA, lef, or cya, growth was inhibited, and
      expression of these virulence genes was inhibited to a proportionately greater
      extent. These data suggest that use of QS inhibitors could represent novel
      therapies for anthrax.

PMID- 15871123
TI  - Growth of Listeria monocytogenes in the guinea pig placenta and role of cell-to
      cell spread in fetal infection.
AB  - Listeria monocytogenes causes foodborne outbreaks that lead to infection in human
      and other mammalian fetuses. To elucidate the molecular and cellular mechanisms
      involved in transplacental transmission, we characterized placental-fetal
      infection in pregnant guinea pigs inoculated with wild-type (wt) or mutant L.
      monocytogenes strains. The wt strain increased in number in the placenta by >1000
      fold during the first 24 h after inoculation--an increase that was unparalleled
      in other maternal organs. The ActA- mutant, which is impaired in cell-to-cell
      spread and attenuated in maternal organs, increased in the placenta by a similar
      amount, although, in fetal infection, the number of ActA- mutant bacteria was 100
      fold lower, compared with that of the wt strain. Furthermore, a mutant impaired
      in vacuolar escape was rapidly eliminated from maternal organs but persisted in
      the placenta. We concluded that cell-to-cell spread facilitates maternal-to-fetal
      transmission. Furthermore, the placenta provides a protective niche for growth of
      L. monocytogenes.

PMID- 15871124
TI  - Excretion of living Borrelia recurrentis in feces of infected human body lice.
AB  - Louse-borne relapsing fever (LBRF), caused by Borrelia recurrentis, is 1 of the
      most dangerous arthropod-borne diseases. Infection is thought to occur through
      louse crushing. Lice feces have not been shown to contain living borreliae. We
      infected 800 body lice by feeding them on a rabbit made spirochetemic by the
      injection of 2 x 106 borreliae. The life span of infected lice was not shortened.
      Once infected, lice remained infected for life but did not transmit borreliae to
      their progeny or to nurse rabbits. B. recurrentis infection was observed
      throughout lice and spread into hemolymph on day 5 after infection. We describe 2
      unprecedented phenomena. In hemolymph, B. recurrentis formed clumps of aggregated
      borreliae. Using immunofluorescence assay, transmission electron microscopy, and
      culture, we detected borreliae excreted in lice feces beginning on day 14 after
      infection. We conclude that, similar to epidemic typhus and trench fever,
      transmission of LBRF may be caused by lice feces.

PMID- 15871125
TI  - Poor vector competence of fleas and the evolution of hypervirulence in Yersinia
      pestis.
AB  - Population genetics and comparative genomics analyses of the pathogenic Yersinia
      species have indicated that arthropodborne transmission is an evolutionarily
      recent adaptation in Yersinia pestis, the agent of plague. We show that the
      infectivity of Y. pestis to its most proficient vector, the rat flea Xenopsylla
      cheopis, and subsequent transmission efficiency are both low. The poor vector
      competence of fleas likely imposed selective pressure that favored the emergence
      and continued maintenance of a hypervirulent Y. pestis clone. In particular, the
      rapidly fatal gram-negative sepsis that typifies plague is a consequence of the
      high threshold bacteremia level that must be attained to complete the
      transmission cycle. Epidemiological modeling predicts that, to compensate for a
      relatively short period of infectivity of the mammalian host for the arthropod
      vector, plague epizootics require a high flea burden per host, even when the
      susceptible host population density is high.

PMID- 15871126
TI  - Induction of tumor necrosis factor- alpha secretion and toll-like receptor 2 and
      4 mRNA expression by genital mucosal fluids from women with bacterial vaginosis.
AB  - BACKGROUND: Bacterial vaginosis (BV) is associated with complications of
      pregnancy and increased susceptibility to human immunodeficiency virus (HIV)
      sexual transmission. METHODS: The ability of genital mucosal fluids from women
      with BV and of microbial flora associated with BV to induce tumor necrosis factor
      (TNF)- alpha secretion and Toll-like receptor (TLR) 2 and TLR4 mRNA expression
      was assessed. RESULTS: Primary peripheral-blood mononuclear cells and THP-1
      monocytic cells secreted TNF- alpha in response to cervicovaginal lavage (CVL)
      samples from women with BV. Mycoplasma hominis and Gardnerella vaginalis also
      stimulated TNF- alpha secretion. Strikingly, CVL samples from women with BV
      induced up to 60-fold increases in TLR4 mRNA expression, compared with CVL
      samples from women without BV and with bacteria not associated with BV. Anti-TNF-
      alpha antibody blocked increases in TLR4 mRNA expression induced by CVL samples
      from women with BV, indicating that TNF- alpha plays a critical role in induction
      of TLR4. Both TLR2 and TLR4 mRNA expression were approximately 60-fold higher in
      cells isolated from the lumen of the genital tract than in cervical mucosal
      tissue, but lumen TLR mRNA levels did not change significantly after BV
      treatment. CONCLUSIONS: These experiments show that genital mucosal fluids and
      certain bacteria from women with BV stimulate TNF- alpha secretion and TLR4 mRNA
      expression, suggesting mechanisms whereby BV affects pregnancy and HIV
      transmission.

PMID- 15871127
TI  - Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage
      human African trypanosomiasis: confirmation from a multinational study (IMPAMEL
      II).
AB  - BACKGROUND: Treatment of late-stage human African trypanosomiasis (HAT) with
      melarsoprol can be improved by shortening the regimen. A previous trial
      demonstrated the safety and efficacy of a 10-day treatment schedule. We
      demonstrate the effectiveness of this schedule in a noncontrolled, multinational
      drug-utilization study. METHODS: A total of 2020 patients with late-stage HAT
      were treated with the 10-day melarsoprol schedule in 16 centers in 7 African
      countries. We assessed outcome on the basis of major adverse events and the cure
      rate after treatment and during 2 years of follow-up. RESULTS: The cure rate 24 h
      after treatment was 93.9%; 2 years later, it was 86.2%. However, 49.3% of
      patients were lost to follow-up. The overall fatality rate was 5.9%. Of treated
      patients, 8.7% had an encephalopathic syndrome that was fatal 45.5% of the time.
      The rate of severe bullous and maculopapular eruptions was 0.8% and 6.8%,
      respectively. CONCLUSIONS: The 10-day treatment schedule was well implemented in
      the field and was effective. It reduces treatment duration, drug amount, and
      hospitalization costs per patient, and it increases treatment-center capacity.
      The shorter protocol has been recommended by the International Scientific Council
      for Trypanosomiasis Research and Control for the treatment of late-stage HAT
      caused by Trypanosoma brucei gambiense.

PMID- 15871128
TI  - Case definitions of clinical malaria under different transmission conditions in
      Kilifi District, Kenya.
AB  - BACKGROUND: Clear case definitions of malaria are an essential means of
      evaluating the effectiveness of present and proposed interventions in malaria.
      The clinical signs of malaria are nonspecific, and parasitemia accompanied by a
      fever may not be sufficient to define an episode of clinical malaria in endemic
      areas. We defined and quantified cases of malaria in people of different age
      groups from 2 areas with different rates of transmission of malaria. METHODS: A
      total of 1602 people were followed up weekly for 2 years, and all the cases of
      fever accompanied by parasitemia were identified. Logistic regression methods
      were used to derive case definitions of malaria. RESULTS: Two case definitions of
      malaria were derived: 1 for children 1-14 years old and 1 for infants (<1 year
      old) and older children and adults (> or =15 years old). We also found a higher
      number of episodes of clinical malaria per person per year in people from an area
      of low transmission of malaria, compared with the number of episodes in those
      from an area of higher transmission (0.84 vs. 0.55 episodes/person/year;
      incidence rate ratio, 0.66 [95% confidence interval, 0.61-0.72]; P<.001).
      CONCLUSIONS: Case definitions of malaria are bound to be altered by factors that
      affect immunity, such as age and transmission. Case definitions may, however, be
      affected by other immunity-altering factors, such as HIV and vaccination status,
      and this needs to be borne in mind during vaccine trials.

PMID- 15871129
TI  - Alterations in the profile of blood cell types during malaria in previously
      unexposed primigravid monkeys.
AB  - Malaria in nonimmune, primigravid women threatens both mother and fetus. We used
      the Plasmodium coatneyi/rhesus monkey model to examine factors associated with
      this. Clinical and immunologic responses during the blood stage of chronic
      malaria (4 months) were evaluated in 8 malaria-naive primigravid (PMI) and 8 age
      matched nulligravid (NMI) infected monkeys, compared with those in 8 primigravid,
      noninfected control monkeys. Although parasitemia levels were similar,
      recrudescence was more frequent and prolonged, and anemia was more severe in PMI
      than in NMI monkeys. During infection, CD2+, CD4+, and CD8+ lymphocyte levels
      were higher in NMI than in PMI monkeys. Monocyte and neutrophil levels were lower
      in PMI than in NMI monkeys. During chronic, untreated malaria, NMI monkeys had a
      B lymphocyte count 23 times greater than that of PMI monkeys. Pregnancy-induced
      immunomodulation, defined as a lack of appropriate cellular responses to malaria,
      was indiscernible until the immune system was challenged by a pathogen.

PMID- 15871130
TI  - Estimating HIV evolutionary pathways and the genetic barrier to drug resistance.
AB  - BACKGROUND: The evolution of drug-resistant viruses challenges the management of
      human immunodeficiency virus (HIV) infections. Understanding this evolutionary
      process is important for the design of effective therapeutic strategies. METHODS:
      We used mutagenetic trees, a family of probabilistic graphical models, to
      describe the accumulation of resistance-associated mutations in the viral genome.
      On the basis of these models, we defined the genetic barrier, a quantity that
      summarizes the difficulty for the virus to escape from the selective pressure of
      the drug by developing escape mutations. RESULTS: From HIV reverse-transcriptase
      sequences that had been obtained from treated patients, we derived evolutionary
      models for zidovudine, zidovudine plus lamivudine, and zidovudine plus
      didanosine. The genetic barriers to resistance to zidovudine, stavudine,
      lamivudine, and didanosine, for the above 3 regimens, were computed and analyzed.
      We found both the mode and the rate of development of resistance to be
      heterogeneous. The genetic barrier to zidovudine resistance was increased if
      lamivudine was added to zidovudine but was decreased for didanosine. The barrier
      to lamivudine resistance was maintained with zidovudine plus didanosine, whereas
      the barrier to didanosine resistance was reduced most with zidovudine plus
      lamivudine. CONCLUSION: Mutagenetic trees provide a quantitative picture of the
      evolution of drug resistance. The genetic barrier is a useful tool for design of
      effective treatment strategies.

PMID- 15871131
TI  - Low accumulation of L90M in protease from subtype F HIV-1 with resistance to
      protease inhibitors is caused by the L89M polymorphism.
AB  - BACKGROUND: This work evaluates the role of subtype F human immunodeficiency
      virus type 1 (HIV-1) protease (PR) substitutions L89M and L90M in viral
      replication and resistance to PR inhibitors (PIs). METHODS: Subtype B and F PR
      genes were subjected to site-directed mutagenesis, to create and reverse the
      methionine at positions 89 and 90. Viruses were re-created in cell culture, and
      their replicative capacity was assessed by fitness assay. Generated viruses were
      also phenotyped for PI resistance. RESULTS: The subtype F clone (89M90L) showed a
      replicative capacity comparable to that of the PI-susceptible subtype B clone
      (89L90L) and was more fit than the L89M mutated subtype B clone (89M90L). Both
      89M90M subtype B and F clones presented the lowest fitness s values. The L89M
      mutation impacted phenotypic resistance to all PIs in half of the subtype F
      isolates but not in the subtype B isolates. Subtype F isolates presented a
      phenotypic profile similar to that of subtype B isolates when the M89L mutation
      was introduced. CONCLUSION: The L89M mutation in subtype F viruses is a high
      genetic barrier to the accumulation of the L90M resistance mutation and can
      function as a resistance mutation, depending on the presence of other
      polymorphisms in the subtype F PR backbone.

PMID- 15871132
TI  - Genetic polymorphisms in CX3CR1 predict HIV-1 disease progression in children
      independently of CD4+ lymphocyte count and HIV-1 RNA load.
AB  - BACKGROUND: The impact of CX3CR1 polymorphisms on human immunodeficiency virus
      type 1 (HIV-1) pathogenesis is controversial, with conflicting reports of their
      role in disease progression in HIV-1-infected adults. METHODS: A cohort of 1055
      HIV-1-infected children were genotyped for 2 CX3CR1 polymorphisms, V/I249 and
      T/M280, and their impact on HIV-1-related disease progression, including central
      nervous system (CNS) impairment, was evaluated. RESULTS: Children with the CX3CR1
      I/I249 genotype experienced more-rapid disease progression (I/I249 vs. V/V249:
      relative hazard [RH], 2.19 [95% confidence interval {CI}, 1.30-3.68], P=.003;
      I/I249 vs. V/I249: RH, 1.77 [95% CI, 1.00-3.14], P=.05) and a trend toward more
      CNS impairment (I/I249 vs. V/V249: RH, 2.19 [95% CI, 1.00-4.78], P=.049; I/I249
      vs. V/I249: RH, 2.02 [95% CI, 0.85-4.83], P=.11). Children with the V249-T280
      haplotype experienced significantly less disease progression (RH, 0.42 [95% CI,
      0.24-0.73]; P=.002) and CNS impairment (RH, 0.39 [95% CI, 0.39-0.22]; P=.001). Of
      note, these effects remained significant after CD4+ lymphocyte count and plasma
      HIV-1 RNA load at baseline were adjusted for and in a longitudinal, multivariate
      analysis. CONCLUSIONS: CX3CR1 genotypes and haplotypes impact HIV-1 disease
      progression independently of CD4+ lymphocyte count and plasma HIV-1 RNA load,
      suggesting that the fundamental role of CX3CR1 in the alteration of disease
      progression might be the recruitment of immunomodulatory cells responsible for
      the control of HIV-1.

PMID- 15871133
TI  - An epidemic of coccidioidomycosis in Arizona associated with climatic changes,
      1998-2001.
AB  - BACKGROUND: Reports of coccidioidomycosis cases in Arizona have increased
      substantially. We investigated factors associated with the increase. METHODS: We
      analyzed the National Electronic Telecommunications System for Surveillance
      (NETSS) data from 1998 to 2001 and used Geographic Information Systems (GIS) to
      map high-incidence areas in Maricopa County. Poisson regression analysis was
      performed to assess the effect of climatic and environmental factors on the
      number of monthly cases; a model was developed and tested to predict outbreaks.
      RESULTS: The overall incidence in 2001 was 43 cases/100,000 population, a
      significant (P<.01, test for trend) increase from 1998 (33 cases/100,000
      population); the highest age-specific rate was in persons > or =65 years old (79
      cases/100,000 population in 2001). Analysis of NETSS data by season indicated
      high-incidence periods during the winter (November-February). GIS analysis showed
      that the highest-incidence areas were in the periphery of Phoenix. Multivariable
      Poisson regression modeling revealed that a combination of certain climatic and
      environmental factors were highly correlated with seasonal outbreaks (R2=0.75).
      CONCLUSIONS: Coccidioidomycosis in Arizona has increased. Its incidence is driven
      by seasonal outbreaks associated with environmental and climatic changes. Our
      study may allow public-health officials to predict seasonal outbreaks in Arizona
      and to alert the public and physicians early, so that appropriate preventive
      measures can be implemented.

PMID- 15871135
TI  - Appropriateness of mathematical modeling of the carriage of multiple strains of
      Staphylococcus aureus.

PMID- 15871134
TI  - Influence of interleukin-10 on Aspergillus fumigatus infection in patients with
      cystic fibrosis.
AB  - Recent evidence suggests that genetic polymorphisms that affect the production of
      interleukin (IL)-10 may play a role in the response to pathogens in cystic
      fibrosis (CF). The present study was designed to investigate a possible
      association between alleles carried at position -1082 in the promoter region of
      the IL-10 gene and clinical data on 378 patients with CF. After adjustment for
      potential confounding variables, a significant relationship was found between the
      -1082GG genotype and both colonization with Aspergillus fumigatus and allergic
      bronchopulmonary aspergillosis. In addition, higher serum levels of IL-10 were
      observed in patients colonized with A. fumigatus. These results suggest that
      polymorphisms in the promoter region of the IL-10 gene may influence the host
      response to A. fumigatus in the context of CF.

PMID- 15871137
TI  - Clearance duration as a predictor of sustained viral response in patients with
      chronic hepatitis C virus genotype 1.

PMID- 15871141
TI  - Using mesenchymal stem cells to home in and deliver anti-tumor therapy with
      interferon-beta.

PMID- 15871139
TI  - Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in
      SLC19A3.
AB  - Biotin-responsive basal ganglia disease (BBGD) is a recessive disorder with
      childhood onset that presents as a subacute encephalopathy, with confusion,
      dysarthria, and dysphagia, and that progresses to severe cogwheel rigidity,
      dystonia, quadriparesis, and eventual death, if left untreated. BBGD symptoms
      disappear within a few days with the administration of high doses of biotin (5-10
      mg/kg/d). On brain magnetic resonance imaging examination, patients display
      central bilateral necrosis in the head of the caudate, with complete or partial
      involvement of the putamen. All patients diagnosed to date are of Saudi, Syrian,
      or Yemeni ancestry, and all have consanguineous parents. Using linkage analysis
      in four families, we mapped the genetic defect near marker D2S2158 in 2q36.3
      (LOD=5.9; theta=0.0) to a minimum candidate region (approximately 2 Mb) between
      D2S2354 and D2S1256, on the basis of complete homozygosity. In this segment, each
      family displayed one of two different missense mutations that altered the coding
      sequence of SLC19A3, the gene for a transporter related to the reduced-folate
      (encoded by SLC19A1) and thiamin (encoded by SLC19A2) transporters.

PMID- 15871142
TI  - LRP6 as a candidate oncogene that regulates tumor proliferation.

PMID- 15871143
TI  - Protein tyrosine phosphatase receptor-type O targeted by methylation in lung
      cancer.

PMID- 15871144
TI  - Pattern of emergency neurologic morbidities in children.
AB  - Neurologic morbidities seen in the children's emergency facility of the
      University of Benin Teaching Hospital, Nigeria, over a five-year period (July
      1996-June 2001) was evaluated to determine the pattern and outcome. Notes and
      ward records of patients with neurologic morbidities were retrieved. Data
      obtained from these sources include age, sex principal diagnosis, duration of
      stay and outcome. Six-hundred-four out of 3,868 patients (15.6%) had neurologic
      morbidity. Children five years of age and under were 466 (77.2%), and modal age
      group was 1-2 years. Febrile convulsion was the most common neurologic morbidity
      seen (35.1%) followed by cerebral malaria (28.0%) and then meningitis (27.0%). An
      increased incidence of cases occurred during the rainy season. Sixty-four out of
      406 with complete records (15.8%) died. Forty-seven (67.2%) died within 24 hours
      of admission. Cerebral malaria and meningitis accounted for all the deaths.
      Preventable infectious diseases are the major causes of emergency neurologic
      morbidities and mortality. The majority die within 24 hours largely due to a
      delay in presentation to the hospital. Effective malaria control and prevention
      of meningitis would reduce the incidence of neurologic morbidities and, if this
      is coupled with health education of the populace on the importance of attending
      health facility early, mortality from these causes would be greatly reduced.

PMID- 15871145
TI  - [Anorexia and bulimia nervosa in adolescence].

PMID- 15871146
TI  - Cannabis as a risk factor for psychosis: systematic review.
AB  - Various lines of evidence suggest an association between cannabis and psychosis.
      Five years ago, the only significant case-control study addressing this question
      was the Swedish Conscript Cohort. Within the last few years, other studies have
      emerged, allowing the evidence for cannabis as a risk factor to be more
      systematically reviewed and assessed. Using specific search criteria on Embase,
      PsychINFO and Medline, all studies examining cannabis as an independent risk
      factor for schizophrenia, psychosis or psychotic symptoms, published between
      January 1966 and January 2004, were examined. Additional studies were also
      reviewed from references found in retrieved articles, reviews, and a cited
      reference search (ISI-Web of Science). Studies selected for meta-analysis
      included: (i) case-control studies where exposure to cannabis preceded the onset
      of schizophrenia or schizophrenia-like psychosis and (ii) cohort studies of
      healthy individuals recruited before the median age of illness onset, with
      cannabis exposure determined prospectively and blind to eventual diagnosis.
      Studies of psychotic symptoms were also tabulated for further discussion. Eleven
      studies were identified examining the relationship between cannabis use and
      psychosis. Seven were included in the meta-analysis, with a derived odds ratio
      (fixed effects) of 2-9 (95 % confidence interval = 2.4-3.6). No evidence of
      publication bias or heterogeneity was found. Early use of cannabis did appear to
      increase the risk of psychosis. For psychotic symptoms, a dose-related effect of
      cannabis use was seen, with vulnerable groups including individuals who used
      cannabis during adolescence, those who had previously experienced psychotic
      symptoms, and those at high genetic risk of developing schizophrenia. In
      conclusion, the available evidence supports the hypothesis that cannabis is an
      independent risk factor, both for psychosis and the development of psychotic
      symptoms. Addressing cannabis use, particularly in vulnerable populations, is
      likely to have beneficial effects on psychiatric morbidity.

PMID- 15871147
TI  - Gamma hydroxy butyrate abuse and dependency.
AB  - The recreational use of gamma hydroxy butyrate (GHB) has gained popularity over
      the last decade. GHB was initially sold as a safe body building and fat burning
      compound. It is now also widely abused by body builders and young ravers. GHB
      attracts young people due the euphoria that it initially produces, and the
      claimed increase in sociability and sexual function (it is also known as liquid
      Ecstasy). Over the last few years, there has been an increase in the number of
      cases of GHB intoxication, dependence and severe withdrawal, as reported in
      medical literature. The situation is complicated by the use of GHB analogues,
      other toxic chemicals that are easily converted into GHB. GHB has recently been
      classified as a class 'C' drug in the UK, but no provisions were made in relation
      to GHB analogues. GHB has been increasingly used in rape cases due to its
      capacity to produce intoxication and amnesia. The management of patients
      dependent on GHB is rather complicated due to the high doses of medication that
      they require to control withdrawal symptoms.

PMID- 15871148
TI  - Stem cell culture shock.

PMID- 15871149
TI  - Microcosmos.

PMID- 15871151
TI  - What if anything is wrong with cloning a human being?

PMID- 15871150
TI  - Mandatory health insurance coverage for cancer clinical trials.

PMID- 15871152
TI  - Symposium: A Celebration of Reproductive Rights: Twenty-Five Years of Roe v.
      Wade.

PMID- 15871153
TI  - A woman's right to choose: wrongful death statutes and abortion rights-
      consistent at last.

PMID- 15871154
TI  - South Carolina bans partial-birth abortions.

PMID- 15871156
TI  - Spirituality and religion in psychiatry practice: parameters and implications.

PMID- 15871155
TI  - Legal forms and reproductive norms.
AB  - This article draws on Pashukanis's concept of legal form and on O'Brien's concept
      of synthetic value to argue that legal form plays a role in reproductive
      relations by constructing legal subjects as the bearers of reproductive
      responsibilities. Pashukanis conceived of legal form as playing a particular role
      in capitalist exchange relations by interpellating subjects as the bearers of
      property rights. O'Brien argued that reproduction's specific value is synthetic
      value, which represents the value of integrating nature and reason in species
      continuity. Synthetic value is distinct from exchange value or emotional value
      which may also attach to reproductive process. By working through Pashukanis's
      method of extracting legal form from specific social relations and by adapting it
      to reproductive relations, an example is provided of how legal form analysis can
      be extended beyond the particular context of capitalist exchange relations. Just
      as legal form constitutes owners and non-owners as legal subjects, so it
      constitutes reproducers and non-reproducers. By tracing the way in which law
      attributes reproductive responsibility, legal form analysis shows us how law
      draws a line between wanting to attribute responsibility and not to attribute it,
      and this contradiction is a hook which social forces such as sexuality, gender,
      race, class and disability can latch on to in pushing legal form to shape
      reproductive responsibilities in a particular way. Each legal form is also
      externally contradicted by other legal forms. When law negotiates a balance
      between the reproductive norms of responsibilities and rights, it demonstrates
      how particular legal forms manage the interaction of different sets of social
      relations, such as reproduction and exchange.

PMID- 15871157
TI  - Appendicitis in childhood hematologic malignancies: analysis and comparison with
      typhilitis.
AB  - BACKGROUND/PURPOSE: Recognition of appendicitis in the child with hematologic
      malignancy may be difficult particularly in the setting of neutropenia and
      multiple medications causing an altered inflammatory response. Typhilitis may
      produce a similar constellation of clinical findings causing further diagnostic
      confusion. This review compares the relative frequency of these two conditions in
      children with hematologic malignancy with a focus on the clinical presentation,
      distinguishing features, surgical management, and outcome for patients with
      appendicitis. METHODS: This institutional review board-approved retrospective
      study evaluated 464 pediatric patients treated for hematologic malignancy at our
      institution from 1997 to 2003. From this cohort, we identified all children with
      a diagnosis of appendicitis or typhilitis. Data include demographics, clinical
      presentation, laboratory studies, and computed tomography (CT) scan findings.
      Groups were compared using the Fisher exact test. Significance was defined as P <
      .05. RESULTS: Eight (1.7%) of 464 children were diagnosed with typhilitis and 7
      (1.5%) with appendicitis. There were no demographic differences between patients
      with appendicitis and typhilitis. Distinguishing clinical features in children
      with typhilitis included presence of fever and diarrhea. Clinical presentation in
      children with appendicitis was atypical in 5 of 7 cases yielding an incorrect
      preoperative diagnosis in all 5. Radiographic evaluation by CT scan accurately
      defined typhilitis, but not appendicitis. An operation was performed on all 7
      children with appendicitis with no operative morbidity or mortality. CONCLUSIONS:
      Appendicitis and typhilitis occur with similar frequency in children with
      leukemia and lymphoma. Typhilitis is accurately diagnosed with clinical findings
      of fever, diarrhea, abdominal pain, and typical CT scan findings. Appendicitis
      tends to present with atypical findings, but can be successfully managed with
      standard surgical care.

PMID- 15871158
TI  - Medical Samaritans: is there a duty to treat?
AB  - This article argues that doctors and other health care professionals should be
      obliged to provide emergency treatment to those in immediate and nearby need
      regardless of the absence of any prior professional relationship between the
      parties. It concludes that the common law should accordingly recognize a specific
      duty of 'medical rescue'. It examines some of the conventional objections to
      affirmative duties, finding them unconvincing in this particular context. It
      draws on two recent appellate decisions, one Australian and the other English,
      for support, as well as on more general arguments concerning moral sentiment,
      professional ethics, public expectation, and respect for human rights.

PMID- 15871159
TI  - Cross-cultural attitudes toward abortion--Greeks versus Americans.
AB  - Using data from 1,494 Greeks and 1,993 Americans, this study finds that social
      abortion attitudes are a separate dimension from physical abortion attitudes.
      According to our structural equation model, abortion attitudes are influenced
      significantly by religiosity and sexual liberalism. The model explains social
      abortion attitudes significantly better than physical abortion attitudes.
      Although the model is applicable to both countries, there are three major
      differences between Greece and the United States. First, in Greece religiosity
      has a smaller impact on sexual liberalism, and sexual liberalism has a much
      weaker impact on both types of abortion attitudes, particularly social abortion
      attitudes. Second, in Greece religiosity is more strongly related to abortion
      attitudes than in the United States, particularly to social abortion attitudes.
      Third, education has a weaker influence in Greece than in the United States.

PMID- 15871160
TI  - Potential human health benefits of antibiotics used in food animals: a case study
      of virginiamycin.
AB  - Risk management of food-animal antibiotics has reached a crucial juncture for
      public health officials worldwide. While withdrawals of animal antibiotics
      previously used to control animal bacterial illnesses are being encouraged in
      many countries, the human health impacts of such withdrawals are only starting to
      be understood. Increases in animal and human bacterial illness rates and
      antibiotic resistance levels in humans in Europe despite bans on animal
      antibiotics there have raised questions about how animal antibiotic use affects
      human health. This paper presents a quantitative human health risk and benefits
      assessment for virginiamycin (VM), a streptogramin antibiotic recommended for
      withdrawal from use in food animals in several countries. It applies a new
      quantitative Rapid Risk Rating Technique (RRRT) that estimates and multiplies
      data-driven exposure, dose-response, and consequence factors, as suggested by WHO
      (2003) to estimate human health impacts from withdrawing virginiamycin. Increased
      human health risks from more pathogens reaching consumers if VM use is terminated
      (6660 estimated excess campylobacteriosis cases per year in the base case) are
      predicted to far outweigh benefits from reduced streptogramin-resistant
      vancomycin-resistant Enterococcus faecium (VREF) infections in human patients
      (0.27 estimated excess cases per year in the base case). While lack of
      information about impacts of VM withdrawal on average human illnesses-per-serving
      of food animal meat precludes a deterministic conclusion, it appears very
      probable that such a withdrawal would cause many times more human illnesses than
      it would prevent. This qualitative conclusion appears to be robust to several
      scientific and modeling uncertainties.

PMID- 15871161
TI  - Acute sinusitis: Finnish clinical practice guidelines.
AB  - These clinical practice guidelines aim at providing assistance mainly to primary
      health care physicians for the diagnosis and management of acute sinusitis.
      Despite the huge impact of upper respiratory infections, criteria for diagnoses
      are often vague, and physicians are often uncertain of their diagnoses. This is
      not surprising, as the sole definition of acute sinusitis is somewhat confusing,
      not to mention the existing discrepancies between treatments, even among
      specialists. The Finnish Society of Otorhinolaryngology has set up a committee to
      evaluate existing data on acute sinusitis and to formulate these guidelines. The
      committee comprised Finnish experts in adult and paediatric otorhinolaryngology,
      clinical microbiology, radiology, paediatrics, and epidemiology. Recommendations
      given are based on the principles of evidence-based medicine, with the level of
      evidence presented.

PMID- 15871162
TI  - Scientific integrity, fidelity and conflicts of interest in research.

PMID- 15871163
TI  - Indirect immunofluorescence and real time PCR for detection of Simkania
      negevensis infection in Danish adults with persistent cough and in healthy
      controls.
AB  - Simkania negevensis is a recently discovered intracellular organism that has been
      associated with respiratory tract infections. To determine the seroprevalence of
      the organism in adult Danes and to study the association between the organism and
      persistent cough, we developed an immunofluorescence assay based on S. negevensis
      infected Hep2 cells for antibody determination and a real time PCR assay for
      direct detection of the organism. Among 100 healthy blood donors, 41 (41%) had
      IgG antibodies to S. negevensis (cut-off titre =1:16) and the antibody level
      increased with increasing age (correlation coefficient 0.124, p=0.037). 80 of 185
      patients (43%) with chronic cough had IgG antibodies to S. negevensis which was
      no different from the 41% in the control population (Chi2=0.13, p=0.72). None of
      the patients or controls had any detectable IgA antibodies to S. negevensis. PCR
      was performed on nasopharyngeal aspirates from a subgroup of 176 patients with
      persistent cough and in none of these was S. negevensis DNA detected. We conclude
      that the seroprevalence of S. negevensis is high in Denmark and positively
      correlated with age. However, we were unable to show an association between S.
      negevensis and persistent cough.

PMID- 15871164
TI  - Antibiotic resistance of urinary pathogens in female general practice patients.
AB  - A cross-sectional study was performed to determine the prevalence of antibiotic
      resistance in women with uncomplicated and complicated lower urinary tract
      infection (UTI) in Germany. In 36 (of 118 invited) general practices, urine
      cultures and resistance testing were performed during 4 months on all women
      presenting with symptoms of UTI. Each patient's symptoms, risk factors and
      treatment were documented. A total of 445 women were included, and their median
      age was 53 y. Complicating factors were present in 27% of women. Urine cultures
      were available for 430 patients. They were sterile in 23%, 53% had 10(5) cfu/ml
      or more, and 24% had 10(2)-10(4) cfu/ml. E.coli was the most frequent pathogen
      (68%), followed by Enterococcus faecalis (10%) and Proteus spp. (10%). E.coli
      resistance levels were 25-40% for amoxicillin, co-amoxiclav, first generation
      oral cephalosporins, trimethoprim and co-trimoxazole. Nine percent were resistant
      to fluoroquinolones. E.coli resistance remained low for nitrofurantoin (2%) and
      third generation oral cephalosporins (3%). Odds for E.coli resistance to most
      antibiotics were 2-5 times higher in patients with complicating factors, and
      increased with age. Resistance levels to all common antibiotics were high even in
      unselected females with UTI in general practices. Older or complicated patients
      had a significantly higher risk for resistance.

PMID- 15871165
TI  - Antimicrobial resistance in urinary bacterial isolates from pregnant women in
      rural Tanzania: implications for public health.
AB  - Treatment of asymptomatic bacteriuria and urinary tract infections in pregnancy
      can prevent adverse outcome for mother and child. However, antimicrobial
      resistance can impede effective chemotherapy. From April 1995 to March 1996,
      urine specimens from 5153 pregnant women in a rural area in northern Tanzania
      were inoculated on dip slides. Bacterial isolates from 101 positive dip slides
      were identified and tested for susceptibility to antimicrobial agents by disc
      diffusion. In total, 107 bacterial isolates were recovered, 71 Gram-negative and
      36 Gram-positive. The most frequent isolates were Escherichia coli (n=27) and
      enterococci (n=15). E. coli isolates showed low rates of resistance to ampicillin
      (17%), mecillinam (9%), cefalexin (0%), nitrofurantoin (4%), trimethoprim
      sulfamethoxazole (0%), trimethoprim (13%) and sulfamethoxazole (0%). Other Gram
      negative bacteria displayed higher rates of resistance to these drugs. All
      enterococcal isolates were sensitive to ampicillin and only 2 were resistant to
      nitrofurantoin. Growth of E. coli from urine culture was correlated with adverse
      outcome of pregnancy (relative risk 4.13, 95% confidence interval 1.50-11.38).
      Antimicrobial susceptibility prevails in urinary isolates of E. coli and
      enterococci from rural areas of northern Tanzania. Susceptibility data from both
      rural and urban areas should be taken into account when planning antibiotic
      policies.

PMID- 15871166
TI  - High plasma HIV load in the CRF01-AE outbreak among injecting drug users in
      Finland.
AB  - An explosive outbreak of HIV-1 caused by the recombinant subtype AE (CRF01-AE)
      was detected in 1998 among Finnish injecting drug users (IDUs). These IDUs were
      compared with IDUs from the Amsterdam Cohort Study (ACS) infected with subtype B,
      to detect possible differences between 2 western IDU cohorts infected with
      different subtypes. Markers for progression (viral load and CD4+lymphocyte count)
      were compared between 93 IDUs with CRF01-AE and 63 IDUs with subtype B. Only
      persons with a seroconversion interval =2 y were included. During 48 months of
      follow-up, both cohorts were similar in CD4+ cell decline, but the Finnish IDUs
      had 0.34-0.94 log10 copies/ml higher viral loads. The Amsterdam IDUs had a low
      viral load (<1000 copies/ml) significantly more often than the Finnish IDUs. The
      difference could not be explained by the use of antiretrovirals. The higher viral
      load may have contributed to the rapid spread of the recombinant virus in the
      Finnish outbreak.

PMID- 15871167
TI  - Acquired antigenicity of DNA after modification with peroxynitrite.
AB  - There are many contaminants affecting human beings, the most important being the
      metabolites of gases in air around us or certain deleterious by products from
      metabolic activity. They are reactive species of nitrogen, oxygen and their
      derivatives. Nitrogen is taken into body as nitrates, nitrites, peptides,
      proteins, etc. and its metabolites include higher oxides of nitrogen and
      peroxynitrite. Although NO is a free radical, it is probably insufficiently
      reactive to attack DNA directly. By contrast its derivatives N2O3, HNO2, ONOO-
      can nitrate, deaminate, cause strand breaks in DNA leading to serious
      consequences including mutations. The study exploits this property of ONOO-, such
      that on modification DNA which in its native form is non-immunogenic acquires the
      ability to elicit immune response in experimental animals. The extent of
      modifications, characterization of induced antibodies along with antigen-antibody
      interactions are studied and analyzed through different techniques.

PMID- 15871168
TI  - Results from a bench marking survey on Supporting Chemical Synthesis and
      Structural Elucidation in the Pharmaceutical Industry.

PMID- 15871170
TI  - Back to basics.

PMID- 15871169
TI  - Payment and participation: a renaissance for Medicare's private health plans?

PMID- 15871171
TI  - GI genomes.

PMID- 15871172
TI  - Medicare program; update of ambulatory surgical center list of covered
      procedures. Interim final rule with comment period.
AB  - This interim final rule with comment period revises the list of procedures that
      are covered when furnished in an ambulatory surgery center (ASC) in accordance
      with section 1833(i)(1) of the Social Security Act. We published our proposed
      deletions and additions in the Federal Register on November 26, 2004. In this
      interim final rule, we respond to public comments and make final additions to and
      deletions from the current list of Medicare approved ambulatory surgical center
      (ASC) procedures.

PMID- 15871173
TI  - Annual Award for Clinical Research in Periodontology.

PMID- 15871174
TI  - The model of the clinical practice of emergency medicine.

PMID- 15871175
TI  - Meet our members. Raul Ramirez, MD. Interview by Samantha Brady.

PMID- 15871176
TI  - A problem-based e-Learning prototype system for clinical medical education.
AB  - The purpose of this system is to establish virtual medical school (VMS) as the
      platform of e-learning center, which integrates collaborative and self-directed
      learning environment by virtual group, classroom and library, and automatically
      converts valuable clinical case from Hospital Information System (HIS) database
      into virtual patient by online authoring tools for problem-based e-learning. In
      this system, the VMS provides a problem-based e-learning environment, and
      utilizes HIS to capture and store valuable clinical cases. All medical students
      and residents now have the opportunity to learn from these typical cases online.
      The VMS at National Taiwan University has the potential to develop into a
      national medical education network for the meditation and provision of
      comprehensive medical resources. The system will use the international standard
      SCORM 1.2 to develop teaching material and assist with the HL7 v2.4, CDA v1.0
      standards to connect Electronic Medical Record (EMR) systems in the hospital. It
      can provide resources sharing among medical centers by using high transportation
      ability of Grid Computing integrated with the broadband video platform, Access
      Grid, and personal multiple point videoconference platform, Multi-video, to
      popularize the application of e-learning in clinical medical education.

PMID- 15871177
TI  - [Preliminary biomarker related to nasopharyngeal carcinoma filtered from the
      whole genome expression profiling involved in microdissection nasopharyngeal
      tissues].
AB  - OBJECTIVE: To filter biomarkers of nasopharyngeal carcinoma (NPC) by constructing
      the homogenesis tissue gene expression profiling with the whole human genome
      GeneChip. METHODS: The epithelium cells of the homogenesis NPC and the pure
      nasopharyngeal normal tissues microdissected from nasopharyngeal biopsy which was
      preserved in the RNAlater were used to isolate RNA and then to harvest the aRNA
      through in vitro transcription, and aRNA prober was labled to hybridize to HG
      U133. plus 2.0, so the expression profiling of each homogenesis tissue could be
      constructed. RESULTS: Some candidate biomarker genes related to the tumorigenesis
      of NPC had been filtered by comparing the expression profiling of NPC samples
      with the expression profiling of normal nasopharyngeal epithelia samples. Any
      genes regarding the metastasis of NPC might have been selected by comparing the
      expression profiling of no-metastasis samples with those of the metastasis
      samples. CONCLUSION: Using the whole genome GeneChip to construct the expression
      profiling for the microdissected homogenesis tissue is effective to filter the
      candidate biomarker genes.

PMID- 15871178
TI  - [Anti-tumor effect of pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy in
      tumor-bearing nude mice].
AB  - OBJECTIVE: To investigate the optimal doses of X-ray irradiation and plasmid
      injection in the anti-tumor effect of the pcDNA3. 1-Egr. 1p-p16 gene combined
      with radiotherapy in vivo. METHODS: We observed the anti-tumor effect of the
      pcDNA3. 1-Egr. 1p-p16 gene combined with radiotherapy with different doses of X
      ray irradiation (2, 10, 20 Gy) and plasmid injection (10, 20, 30 microg) in nude
      mice with JF-305 pancreatic carcinoma, and detected the expression of p16 in
      tumor by RT-PCR. RESULTS: The tumor growth rate of the nude mice irradiated
      locally with 20 Gy X-rays after the plasmid injection was significantly lower (P
      < 0.05 ) than that of the nude mice irradiated locally with 2 Gy or 10 Gy X-ray 3
      days after the irradiation. The tumor growth rate of the nude mice injected
      locally with 20 microg or 30 microg plasmid was significantly lower (P <0.05 )
      than that of the nude mice injected locally with 10 microg plasmid. Both pcDNA3.
      1-Egr. 1p-p16 group and pcDNA3. 1-Egr. 1p-p16 +20 Gy group had p16 mRNA
      expression, but the mRNA level of pcDNA3. 1-Egr. 1p-p16 +20 Gy group was higher
      than that of pcD- NA3. 1-Egr. 1p-p16 group. CONCLUSION: In the pcDNA3. 1-Egr. 1p
      p16 gene combined with radiotherapy in vivo the optimal dose of X-ray irradiation
      was 20 Gy and the optimal dose of plasmid injection was 20 microg. The anti-tumor
      effect of pcDNA3. 1-Egr. 1p-p16 combined with radiotherapy is better than that of
      radiotherapy or gene therapy alone, which may be related with the enhanced p16
      expression in tumor after the irradiation.

PMID- 15871179
TI  - [Preliminary proteome analysis of mouse embryonic fibroblast conditioned medium].
AB  - OBJECTIVE: To perform the proteome analysis of conditioned medium prepared from
      mouse embryonic fibroblast feeder layers by 2-dimensional (2D) electrophoresis
      and mass spectrometry and to find out the possible differentiation-inhibitory
      factor in conditioned medium. METHODS: Feeder layers were prepared by 60Co gamma
      irradiation on mouse embryonic fibroblast. Insulin-transferrin-sodium selenite
      supplemented medium was used to culture the feeder layers for 24 hours. The
      condioned medium prepared from mouse embryonic fibroblast feeder layers were made
      into powder by lyophilization, the redissolved solution was applied to Sephadex G
      50 gel filtration chromatography, and then cold acetone was used to precipitate
      the proteins in the eluted solution. The protein samples were applied to 2D
      electrophoresis. The 2D images were analyzed by 2D image analysis software.
      Selected protein spots were digested by trypsin, analyzed by mass spectrometry,
      and then searched against the NCBInr batabase using Mascot MS/MS Ions Search.
      RESULTS: The protein samples extracted from mouse embryonic fibroblast feeder
      layers conditioned medium could be used for 2D electrophoresis. On 2D images,
      there were (221+/-67) spots. Most of the proteins were located in the region of
      MW 20 approximately 70 kD, pI 4 approximately 8. Using mass spectrometry, we
      preliminarily identified 13 spots: 3 keratins, 3 transferrins, 1 trypsin
      precursor, 2 unknown proteins (3 spots), 1 connexin 46, 1 beta-galactoside
      binding protein, and 1 secreted protein, acidic and rich in cysteine. CONCLUSION:
      Conditioned medium prepared from mouse embryonic fibroblast feeder layers contain
      beta-galactoside binding protein and secreted protein, acidic and rich in
      cysteine.

PMID- 15871180
TI  - [Construction and bio-activity of the chimeric protein of BMP2-EGFP].
AB  - OBJECTIVE: To construct the recombined retroviral expression vector of
      BMP2/pLEGFP and investigate the bio-activity of the expressed chimeric protein.
      METHODS: The recombinant vector constructed by gene recombinant technology was
      analyzed by restriction enzyme digestion and PCR. BMP2/pLEGFP was transfected
      into COS-7 cells with liposome transfection reagents for transient expression.
      The expression of chimeric protein BMP2/EGFP was identified by fluorescent
      microscope and Western blotting. The bio-activity was examined by the cellular
      activity and animal heterotopic osteogenesis experiment. RESULTS: The recombinant
      plasmid proved successful by restriction enzyme digestion and PCR. The expression
      of the chimeric protein was shown by fluorescent microscope and Western blotting.
      The chimeric protein had the double bio-activities of BMP2 and EGFP identified by
      the cellular activity and animal heterotopic osteogenesis tests. CONCLUSION: The
      recombinant vector of BMP2/pLEGFP is successfully constructed by the gene
      recombinant technology and its chimeric protein has double bioactivities of BMP2
      and EGFP.

PMID- 15871181
TI  - [Ophthalmoparalysis: cause by diabetes mellitus or Tolosa-Hunt syndrome?].

PMID- 15871182
TI  - [Development and evaluation of quality of life scale for patients with type 2
      diabetes mellitus].
AB  - OBJECTIVE: To develop a specific quality of life scale for Chinese Type 2
      diabetes mellitus (DM) patients. METHODS: According to the quality of life
      definition of WHO, we used methods adhered to the rigorous guidelines of
      instrument development in item pool formation, item selection and scale
      validation with the data of 236 Type 2 diabetic patients recruited. RESULTS: An
      87-item Quality of Life Scale for patients with Type 2 DM-prior test version (
      DMQLS), including 5 domains ( disease, physical, social, psychological, and
      satisfaction ) was developed and showed good reliability and validity. The
      disease domain made up of Type 2 diabetes mellitus-specific sub-scale and the
      other 4 domains formed the generic sub-scale for adults. The test-retest
      correlation coefficient, Cronbach's Alpha coefficient and split-half reliability
      coefficient of DMQLS were 0.996, 0.969 and 0.879, respectively. Twenty-one common
      factors were extracted according to the conceptual model. The scale's
      correlations with SF-36 and Diabetes Quality of Life Measure ( DQOL ) were 0.763
      and 0.658. DMQLS could discriminate among those with different quality of lives.
      CONCLUSION: DMQLS is reliable, valid and sensitive, and can be used to evaluate
      the curative effect of Type 2 diabetic patients.

PMID- 15871183
TI  - [Development of the quality of life scale specific for patients with benign
      prostatic hyperplasia].
AB  - OBJECTIVE: To develop a specific quality of life (QOL) scale for Chinese patients
      with benign prostatic hyperplasia (BPH). METHODS: The scale was developed with
      the programmed decision methods. The item pool was certified by experts. Five
      methods were used in item selection after a pilot study for which 256 BPH
      patients had been recruited. The scale was evaluated by its reliability and
      validity. RESULTS: We formed a 27-item quality of life scale specific for
      patients with benign prostatic hyperplasia prior test version (BPHSQL). The test
      retest correlation coefficient and Cronbach's alpha coefficient of BPHSQL were 0.
      774 and 0. 945. The structure of the scale was similar to the theory
      construction. The scale's correlation coefficients with criteria ranged from
      0.531 to 0.700. BPHSQL could well discriminate the quality of life between BPH
      and non-BPH patients as well as patients with different degrees of symptoms,
      different sources and patients with or without urethral catheters. CONCLUSION:
      BPHSQL is reliable, valid and sensitive, and will be a convenient tool in
      clinical research to provide advice on different treatments for different
      patients.

PMID- 15871184
TI  - [HSP70 inhibits smac release from the mitochondria and protects against H2O2
      induced apoptosis in C2C12 myogenic cells].
AB  - OBJECTIVE: To observe whether HSP70 could protect against H2O2-induced apoptosis
      in C2C12 myogenic cells by inhibiting Smac release from the mitochondria.
      METHODS: HSP70 gene and full length Smac gene was transiently transfected in
      C2C12 myogenic cells by lipofectamine and the protein levels of HSP70 and Smac
      were analysed by Western blotting. Hoechst 33 258 staining was used to examine
      cell morphological changes and to calculate percentage of apoptotic nuclei. DNA
      ladder pattern on agarose gel electrophoresis was used to observe the DNA
      fragmentation. Activities of caspase-3 and caspase-9 were assayed with Western
      blotting. The release of Smac from the mitochondria to the cytoplasm was observed
      by immunofluorescence. RESULTS: H2O2 ( 0.5 mmol/L ) activated caspase-3, caspase
      9 8 h after the treatment and specific morphological changes of apoptosis 12 h
      after the treatment, and overexpression of Smac significantly promoted H2O2
      induced activation of caspase-3, caspase-9 and apoptosis in C2C12 myogenic cells.
      HSP70 overexpression significantly inhibited H2O2-induced and Smac-promoted
      apoptosis, as shown by no specific DNA ladder pattern in agarose gel
      electrophoresis, decrease of percentage of apoptotic nuclei, and marked
      inactivation of caspase-3 and caspase-9. HSP70 could inhibit the release of Smac
      from the mitochondria to the cytoplasm 2 h after the treatment by H2O2.
      CONCLUSION: HSP70 inhibits Smac release from the mitochondria and protects
      against H2O2-induced apoptosis in C2C12 myogenic cells.

PMID- 15871185
TI  - [Effects of long-term estrogen replacement treatment on the blood pressure and
      expression of IR and IRS-1 in myocardium].
AB  - OBJECTIVE: To determine the effects of long-term estrogen replacement treatment
      on blood pressure and expressions of insulin receptor (IR) and insulin receptor
      substrate-1 ( IRS-1) in myocardium. METHODS: Fifty female SD rats were randomly
      divided into 3 groups. And then sham ( n = 16), ovariectomy (OVX, n = 17), and
      estrogen replacement treatment group (OVX + E2, n = 17) were established.
      Systolic blood pressure of tail artery was determined by tail-cuff technique
      before the operation and on week 12 after the operation. The expressions of IR
      and IRS-1 were measured by RT-PCR in myocardium of SD rats. RESULTS: Blood
      pressure [ (118.75+/-2.77) mmHg] in OVX was significantly higher than that in the
      sham [ ( 103.86+/-1.84) mmHg, P < 0.05 ] and OVX + E2 [( 107.83+/-3.24) mmHg, P <
      0.05 ] rats. Expression of IRS-1 in OVX group was significantly lower ( 1.2588+/
      0.1045)than that in the sham(2.2089+/-0.0988, P <0.05) and OVX + E2 groups (
      1.9100+/-0.1230, P <0.05 ). However, there was no difference on blood pressure
      and expression of IRS-1 between sham and OVX + E2 groups (P > 0.05 ). The
      difference of IR expression has no statistical significance among the 3 groups.
      CONCLUSION: Long-term estrogen replacement treatment might protect cardiovascular
      system through decreasing the blood pressure and inducing the expression of IRS-1
      in myocardium. However, plasma estrogen level doesn't significantly influence the
      IR expression.

PMID- 15871186
TI  - [Effects of long-term estrogen replacement treatment on the expression of bcl-2
      and H-ras in rat endometrium].
AB  - OBJECTIVE: To investigate the effects of long-term estrogen replacement treatment
      (ERT) on the expression of bcl-2 and H-ras in rat endometrium. METHODS: Thirty 5
      month-old SD female rats were randomly divided into 3 groups: Control group (
      sham operated and vehicle injected, n 10) , OVX group (OVX operated and vehicle
      injected, n = 10) , and ERT group (OVX operated and 17 beta-estradiol injected, n
      = 10). The rats were killed in the 13th week and the uteri were isolated and
      weighed, pathologically analyzed, and we measured the thickness of the
      endometrium. Immunochemistry and in situ hybridization analysis were used to
      examine the changes of bcl-2 and H-ras mRNA and Bcl and H-ras protein expression
      in the endometrium of the rats. RESULTS: Uterine weight and endometrial thickness
      of OVX decreased much more than those of the control (P <0.01 ) and ERT rats (P <
      0.01). One simple hyperplasia and one squamous metaplasia of endometrium were
      found in ERT rats. Quantitatively, bcl-2 and H-ras mRNA and Bcl and H-ras protein
      level of ERT were higher than those of OVX rats (P < 0.01 ), and there were no
      statistical significances between the ERT group and the control rats. CONCLUSION:
      Long-term estrogen replacement can keep the endometrium from atrophy, and lead to
      the genesis of simple hyperplasia and squamous metaplasia of the endometriun,
      which can increase the risk of endometrial carcinomas. Estrogen may inhibit
      apoptosis and promote the proliferation of endometrial cells through increasing
      the expression of bcl-2 and H-ras mRNA and Bcl-H-ras proteins.

PMID- 15871187
TI  - [Effect of xiaokeling concentration fluid on mRNA expression of insulin-like
      growth factor-1 in sciatic nerve of Streptozotocin-induced diabetic rats].
AB  - OBJECTIVE: To investigate the effect of xiaokeling concentration fluid on insulin
      like growth factor-1 (IGF-1) mRNA expression in sciatic nerve of Streptozotocin
      induced diabetic rats. METHODS: Thirty diabetic rats were randomly divided into
      model group, mecobalamin tablets group, and xiaokeling concentration fluid group.
      The IGF-1 mRNA level in sciatic nerve of each group was determined after 8 weeks
      by relative quantity RT-PCR. RESULTS: The IGF-1 mRNA level in sciatic nerve of
      diabetic rats between xiaokeling concentration fluid group, mecobalamin tablets
      group and normal group showed no significant difference ( P = 0.213, P = 0.822, P
      = 0.304 ), while was significantly higher than that of the model group ( P < 0.05
      ). IGF-1 mRNA level was negatively correlated with the level of blood sugar (P <
      0.05). CONCLUSION: IGF-1 mRNA level decreased in sciatic nerve of diabetic rats.
      Xiaokeling concentration fluid can increase the IGF-1 mRNA level in sciatic nerve
      of diabetic rats. Xiaokeling concentration fluid is involved in the regulation of
      IGF-1 expression, and probably prevents diabetic peripheral neuropathy from
      deteriorating.

PMID- 15871188
TI  - [Expression of brain-derived neurotrophic factor in hippocampus of ovariectomized
      mouse].
AB  - OBJECTIVE: To explore the expression of brain-derived neurotrophic factor (BDNF)
      in the hippocampus after ovariectomy in mice. METHODS: BDNF levels were detected
      by immunohistochemistry combined image analysis in hippocampal CA regions and
      dentate gyrus of ovariectomized mice. RESULTS: The expression of BDNF in
      hippocampus of mice decreased significantly after the ovariectomy after 4 days.
      The recovery BDNF expression started 14 days after the ovariectomy and after 28
      days, the expression of BDNF in hippocampus recovered to the normal level.
      CONCLUSION: The decrease of estrogen in ovariectomized mice can weaken the
      expression of BDNF in hippocampus during the early stage.

PMID- 15871189
TI  - [Changes of serum asymmetric dimethylarginine in essential hypertension before
      and after the treatment].
AB  - OBJECTIVE: To investigate the relationship between serum asymmetric
      dimethylarginine (ADMA) and blood pressure as well as target organ damage in
      essential hypertension, and to evaluate the effects of enalapril and losartan on
      them. METHODS: Forty-two newly diagnoszed patients with essential hypertension
      were randomly divided into enalapril-treated group and losartan-treated group.
      Serum ADMA, L-arginine, and nitric oxide( NO) were measured before and after the
      treatment for 8 weeks. Twenty-three healthy volunteers were included as control
      subjects. RESULTS: The concentrations of ADMA and L-arginine in serum were
      significantly higher but the level of nitric oxide was relatively lower ( P <
      0.01 ) in hypertensive patients than those in control subjects. Serum ADMA was
      higher in different levels of blood pressure and target organ damage. Treatment
      with enalapril or losartan for 8 weeks not only reduced blood pressure but also
      decreased serum ADMA (P <0.01 ). Furthermore, treatment with these drugs also
      increased the level of serum nitric oxide but didn't change the level of L
      arginine. CONCLUSION: The concentrations of serum ADMA and L-arginine were
      increased, but the level of nitric oxide was decreased in the early stage of
      essential hypertension. Both enalapril and losartan could ameliorate the
      endothelial function by reducing the concentration of ADMA.

PMID- 15871190
TI  - [Assessment of left ventricular systolic and diastolic function by Doppler tissue
      imaging in patients with chronic heart failure].
AB  - OBJECTIVE: To investigate the application of pulsed-wave Doppler tissue imaging (
      PW-DTI) in evaluating left ventricular systolic and diastolic function in
      patients with chronic heart failure (CHF). METHODS: Mitral annular velocities
      (MAV) were measured by PW-DTI in 35 patients with CHF and 25 healthy subjects.
      Traditional indices for evaluating the global left ventricular function by
      conventional echocardiography were also studied as a comparison. RESULTS: Peak
      systolic, peak early diastolic, peak late diastolic mitral annular velocities (
      Sa, Ea, Aa), and Ea/Aa ratio progressively decreased in CHF patients compared
      with the healthy subjects (P <0.01 ). Sa of the mitral annulus correlated
      linearly with the left ventricle ejection fraction (LVEF) (r =0.890, P < 0.01).
      Compared with the healthy subjects, Ea in all 3 subgroups of diastolic
      dysfunction in the CHF group significantly decreased (P <0.01). Aa in 2 subgroups
      (pseudonormal filling and restrictive filling) decreased (P < 0.01 ) and the
      decreased Ea/Aa was found in the delayed relaxation and pseudonormal filling
      subgroups compared with the healthy subjects (P<0.001). CONCLUSION: MAV measured
      by PW-DTI can be used for assessing the left ventricular systolic and diastolic
      function in CHF patients.

PMID- 15871191
TI  - [Protective mechanism of ischemic preconditioning to the lung ischemia
      reperfusion injury].
AB  - OBJECTIVE: To determine the protective mechanism of preconditioning to the lung
      injury induced by ischemia-reperfusion. METHODS: Twelve pigs were randomly
      divided into 2 groups: control group ( Group C) and ischemic preconditioning
      group ( Group IP). The concentration of superoxide distrautase (SOD) and
      malondialdehyde (MDA) in circuit were checked before and after the perfusion to
      reflect the lipid peroxidation in the lungs. Left lung biopsies were performed
      immediately after the perfusion and 1 hour postperfusion for histologic
      examination. The ICAM-1 expression was assessed by immunohistochemical analysis
      with Envision method and the mRNA expression of ICAM-1 was analyzed by RT-PCR.
      RESULTS: SOD in Group IP was much higher than that in Group C (P < 0.01 ). MDA in
      Group IP was much lower than that in Group C ( P < 0.01 ). The lung histologic
      examination showed that Group C was significantly more serious than Group IP in
      pulmonary edema, inflammatory cell infiltration, mild focal hemorrhage, and
      alveolar disruption. The expression of ICAM-1 of lung tissue obviously decreased
      in Group IP than that in Group C (P <0.01 ). The expression of ICAM-1 mRNA of
      lung tissue was significantly lower in Group IP than that in Group C (P < 0.01 ).
      CONCLUSION: Lung ischemic preconditioning can reduce the lung injury. The
      mechanisms of the protective effects of the IP may be related to the increase of
      SOD and the decrease of MDA. The preconditioning down-regulated the ICAM-1
      expression is one of the mechanisms in reducing the lung injury.

PMID- 15871192
TI  - [Clinical significance of serum vascular endothelial growth factor and
      interleukin-6 in multiple myeloma].
AB  - OBJECTIVE: To investigate the clinical significance of the changes of vascular
      endothelial growth factor ( VEGF ) and interleukin-6 ( IL-6 ) level in multiple
      myeloma (MM), solid tumor following bone metastasis. METHODS: Thirty- seven MM
      patients, including 7 in Stage I , 8 in Stage II , 22 in Stage III, 8 solid tumor
      with bone metastasis patientsly, and 17 healthy controls were enrolled in this
      study. The serum VEGF and IL-6 levels were determined by ELISA. RESULTS: Serum
      VEGF and IL-6 concentrations in patients with MM and solid tumor were
      significantly higher than those of the healthy controls (P <0.01 ), and the VEGF
      level was higher in MM than in solid tumor with bone metastasis. There was
      significant difference in VEGF and IL-6 levels in various clinical stages of MM.
      VEGF levels in Stage II were significantly higher than in Stage I (P < 0.05 ) and
      IL-6 levels in Stage II were significantly higher than in Stage I (P < 0.05). The
      levels of IL-6 showed great difference according to bone lesion scores (P <
      0.05). There was a positive correlation between IL-6 and serum calcium or C
      reactive protein( P <0.01) , and there was a positive correlation between VEGF
      and serum Cr or urinary Bene-Jones protein lambda (P < 0.01 ). The IL-6 levels
      had significant differences between patients with the normal serum CRP, serum
      calcium, and beta2-MG and patients with abnormal ones (P < 0.05). VEGF levels
      showed significant differences between the patients with normal serum Cr, serum
      calcium Bene-Jones protein lambda, and urinary Bene-Jones protein lambda and
      patients with abnormal ones (P < 0.05). CONCLUSION: Serum VEGF and IL-6 levels
      are helpful to diagnose the clinical stages, and understand bone lesion and
      serevity of MM.

PMID- 15871193
TI  - [Therapeutic effect of fuzheng yangying oral solution on immune-induced aplastic
      anemia mice].
AB  - OBJECTIVE: To observe the effect of fuzheng yangying oral solution on bone marrow
      proliferation and serum interleukin 2 in immune-induced aplastic anemia mice.
      METHODS: The immune-induced aplastic anemia mouse models were built up, and then
      were divided into 4 groups by randomized allocation. The models were fed with
      physical salts (Group A, n = 10 ), fuzheng yangying oral solution (Group B, n =
      10), cyclosporin A (Group C, n = 10), and fuzheng yangying oral solution plus
      cyclosporin A (Group D, n =10), respectively. Another 10 healthy mice served as
      controls (Group E). The changes in blood cells, bone marrow karyocyte count,
      marrow hematopoietic tissue capacity, and serum interleukin 2 level were
      observed. RESULTS: The blood cells, bone marrow karyocyte count, and marrow
      hematopoietic tissue capacity in Group A were significantly lower than those of
      Group E (P < 0. 05) ; those in the 3 treated groups (Group B, C, and D) were
      significantly higher than those of Group A ( P < 0. 05 ); and Group D was the
      highest ( P < 0. 05 ). There were no significant difference between Group B and C
      ( P > 0. 05 ). The level of interleukin 2 in Group A was obviously higher than
      that of Group E (P < 0. 05 ); The levels of interleukin 2 in the 3 treated group
      ( Group B, C, and D) were significantly lower than those of Group A ( P < 0. 05
      ); and Group D was the lowest ( P < 0. 05). There was no significant difference
      in the level of interleukin 2 between Group B and C ( P < 0. 05). CONCLUSION:
      Fuzeng yangying oral solution can impove the bone marrow proliferation and reduce
      the level of serum interleukin 2 in immune-induced aplastic anemia mice.

PMID- 15871194
TI  - [Clinical study on bispectral index in monitoring the depth of desflurane
      anesthesia in the elderly].
AB  - OBJECTIVE: To evaluate the values of bispectral index (BIS) in mornitoring the
      depth of desflurane anesthesia in the elderly by observing the changes of BIS at
      various end-tidal desflurane concentrations. METHODS: BIS was used to monitor the
      depth of desflurane anesthesia in the elderly without surgery stimulation. Forty
      ASA physical status I approximately III patients undergoing general anesthesia
      were divided into 2 groups with 20 in each group:Group Elderly ( > or =65 years)
      and Group Youth ( 18 approximately 55 years). Anesthesia was induced with
      propofol 2. 0 mg/kg and vecuronium 0. 1 mg/kg including the endotracheal topical
      anesthesia with 2% lidocaine. After the desflurane in oxygen, each concentration
      of desflurane was maintained for 20 minutes. The changes of mean arterial blood
      pressure (MAP), heart rate (HR) and BIS were recorded simultaneously. The
      timepoints setting for observation were: preanesthesia, 2 minutes after the
      anesthesia, endotracheal intubation, 2 minutes after the intubation, and end
      tidal concentration of desflurane at 0. 6 MAC, 1.0 MAC and 1. 3 MAC. RESULTS:
      During anesthesia of desflurane, MAP and HR did not change significantly in the 2
      groups with increasing end-tidal desflurane concentration from 0. 6 MAC to 1. 3
      MAC (P > 0.05). BIS decreased significantly than that at preanesthesia in the 2
      groups during anesthesia of desflurane ( P < 0.05 ). The changes of BIS were
      different in the 2 groups during the whole anesthesia (P < 0.05). As the
      concentration of desflurane increased, BIS decreased gradually but there were no
      significant changes on BIS in the 2 groups ( P > 0. 05 ). In general, BIS highly
      correlated with the end-tidal desflurane concentration. The coefficient of
      product-moment correlation (r) between BIS and the end-tidal desflurane
      concentration was -0. 996 and -0. 946 in Group Elderly and Youth (P < 0. 05 ).
      CONCLUSION: BIS highly correlates with the end-tidal desflurane concentration
      which is used to evaluate the depth of desflurane anesthesia in the elderly and
      youth. There is different depth of anesthesia by BIS in the elderly or youth at
      the same end-tidal desflurane concentration.

PMID- 15871195
TI  - [Effects of fentanyl on cytokines and MDA during cardiopulmonary bypass in
      patients undergoing valve replacement].
AB  - OBJECTIVE: To investigate the effect of fentanyl on cytokines and MDA in valve
      replacement surgery during cardiopulmonary bypass ( CPB). METHODS: Thirty ASA II
      approximately III adult patients scheduled for cardial valve replacement were
      randomly divided into 3 groups: Group A (fentanyl 30 microg/ kg), Group B
      (fentanyl 60 microg/kg), and Group C (fentanyl 100 microg/kg). Anesthesia was
      induced with medazalam 0.1 mg/kg, fentanyl 10 microg/kg and vecuronium 0.1 mg/kg
      Administered intravenously. After tracheal intubation the patients were
      mechanically ventilated with pure oxygen. P(ET)CO2 was maintained between 35
      approximately 45 mmHg. Anesthesia were maintained with fentanyl infusion combined
      with intermittent intravenous bolus of midazolam and vecuronium. MAP, CVP, HR,
      P(ET)CO2, SPO2, nasal and rectal temperature were monitored continuously.
      Remained dose of fentanyl was infused before the CPB. Blood Samples were taken
      before the operation (T1 ), before the CPB ( T2 ), 30 min after aortic declamping
      (T3 ) , 2 h after aortic declamping (T4 ), and 24 h (T5 ) after the operation for
      determination of plasma levels of tumor necrosis factor (TNF-alpha), interteukin
      IL-6 and IL-10, MDA. RESULTS: There was no significant change in the age, body
      weight, aortic cross-clomp time, CPB time, and operation time. Levels of TNF
      alpha, IL-6, IL-10 and MDA after the CPB in the 3 groups were significantly
      higher compared with T, (P <0.01 ), TNF-alpha, IL-6 and MDA levels at T3, T4 were
      significantly lower in Group B and C than those in Group A. IL-10 levels at T4,
      T5 were significantly higher in Group B and C than those in Group A, but levels
      of TNF-alpha, IL-6, IL-10 and MDA in Group B were not significantly different
      compared with those in Group C. The duration of stay in the ICU and time of
      endotracheal extubation were significantly longer in patients of Group C than
      those of Group A and B. CONCLUSION: CPB leads to a proinflammatory and
      antiinflammatory response, as well as oxygen free radicals release. Larger dose
      fentanyl seemed to be effective in reducing CPB-induced inflammatory response and
      ischemic reperfusion injury, but the effect was not dependent on dose while
      fentanyl dose reaching some value, at the same time the duration of stay in ICU
      and time of endotracheal extubation is longer.

PMID- 15871196
TI  - [Clinical research of hyperbaric, isobaric, and hypobaric solutions of
      bupivacaine in continuous spinal anesthesia].
AB  - OBJECTIVE: To compare the anesthesia properities of hyperbaric bupivacaine with
      those of isobaric and hypobaric solutions when administered in the supine
      position undergoing hip surgery or lower limb surgery using continuous spinal
      anesthesia. METHODS: Sixty patients( ASA I approximately III ) scheduled for hip
      or lower limb surgery were randomly divided into 3 groups with 20 patients in
      each group: Group A: 0. 375% hyperbaric bupivacaine solutions; Group B :0.375%
      isobaric bupivacaine solutions; and Group C: 0. 375% hypobaric bupivacaine
      solutions. The following variables were measured every 2 minutes during the first
      30 minutes after the intrathecal injection : the onset time of sensation block,
      the highest plane of analgesia, the time to reach complete motor blockade, and
      the plane of analgesia and the extent of lower extremities' movement (modified
      bromage score, BMS) at different time after the administration. Meanwhile the
      changes of hemodynamics were recorded. RESULTS: There was no statistical
      difference among the basic conditions ( P > 0.05). The onset time of sensation
      block, and the time to reach complete motor blockade, and the time receiving the
      highest sharp pain sensory block in Group A were significantly shorter than those
      in Group B and Group C ( P < 0.01 ). The plane of analgesia obtained in the
      hyperbaric group was significantly higher than in both the isobaric and the
      hypobaric groups ( P < 0.01). The mean arterial pressure(MAP) , HR in the
      hyperbaric group decreased significantly after the intrathecal injection( P <
      0.05 ). CONCLUSION: The 0.375% Isobaric bupivacaine used during contiuous spinal
      anesthesia in the supine position produces a suitable and a more "controllable"
      anesthesia, but a minimum dosage of 10 approximately 12.5 mg is required to
      obtain adequate anesthesic conditions with moderate hemodynamic changes and
      satisfying analgesia effects. Under similar conditions, 0. 375% hyperbaric
      bupivacaine produces major hemodynamic consequences with high cephalad spread and
      0. 375% hypobaric bupivacaine has a too long onset time.

PMID- 15871198
TI  - [A case of stromal tumors of ligamentum latum uteri].

PMID- 15871197
TI  - [Behaviorial observation of ropivacaine in continuous spinal anesthesia and Ca2+
      content of spinal cord in rats].
AB  - OBJECTIVE: To observe the behaviour and Ca2+ content of spinal cord in rats after
      continuous spinal anesthesia administration of different densities and doses of
      ropivacaine in SD rats. METHODS: Twenty-four male SD rats weighing 220
      approximately 280 g were anesthetized. A polyurethane microspinal catheter was
      inserted into the lumbar subarachnoid space 8 cm according to the method of
      Yaksh's. The animals were randomly divided into 4 groups of 6 each: in group N
      the rats were given normal saline 40 microl intrathecally every one and half
      hours for 3 times; in group R1, 0.5% ropivacaine was given; in group R2 0.75%
      ropivacaine and in group R3 1% ropivacaine was given. The activity of rats was
      observed. After 6 hours rats were perfused with 4% formamint through the
      ascending aorta. The rats were sacrificed and L1 approximately 2 segment of
      spinal cord was immediately removed for Ca2+ content examination. RESULTS: A
      total hind limbs paralysis was seen at 30 seconds and intramuscular strain
      gradually came back from 30 to 90 minutes after the intrathecal administration of
      ropivacaine in all rats. The recovery of motor black was remarkably different in
      group R1, R2, and R3 (P < 0.05). The Ca2+ content of spinal cord was
      significantly higher in group R3 than that in group R1 and R2 (P < 0.05 ).
      CONCLUSION: There is no significant change of motor black time and it is related
      to drug dose for 0.5% , 0.75% and 1% ropivacaine in continuous spinal anesthesia.
      1% ropivacaine may increase Ca2+ content in spinal cord.

PMID- 15871199
TI  - [Expression of cylooxygenase-2 in endometriosis].
AB  - OBJECTIVE: To investigate the expression of cyclooxygense-2 (COX-2) in eutopic
      and ectopic endometrium in ovarian endometriosis. METHODS: Thirty patients with
      ovrian endometriosis, 10 with ovarian chocolate cysts and 27 normal controls were
      enrolled it determine the expression of COX-2 immunohistochemically in eutopic or
      ectopic endometrium or healthy endometrial tissues. RESULTS: The
      immunoreactivities of COX-2 were found in epithelial cells and stromal cells in
      eutopic endometrium. The expression of COX-2 in the epithelial cells in the
      secretory phase was higher than that in the proliferative phase in the control
      group and ovarian endometriosis group (P <0. 05). But the expression of COX-2 in
      stromal cells in the control group and ovarian endometriosis group showed no
      cyclic changes throughout the menstrual cycle (P > 0. 05). The expression of COX
      2 in eutopic and ectopic endometrium in the ovarian endometriosis group was
      higher than that in the control group (P <0. 05) , hut we did not find
      significant difference between the eutopic and ectopic endometrium in the ovarian
      endometriosis group (P > 0. 05). CONCLUSION: The increased COX-2 expression in
      eutopic and ectopic endometrium in ovarian endometriosis may he related to its
      pathology.

PMID- 15871200
TI  - [Experimental study of spirulina platensis in treating allergic rhinitis in
      rats].
AB  - OBJECTIVE: To determine the therapeutic effect of spirulina platensis in allergic
      rhinitis (AR). METHODS: Ovalbumin sensitized white rats used as AR animals were
      treated with spirulina platensis (SPP). At the end of the treatment, the
      differences in the behavior science were observed; the changes in the nasal
      mucosa and mast cell degranulation were studied pathologically; and the levels of
      serum histamine and total immunoglobulin (Ig) E were determined by enzyme-linked
      immune sorbent assay. RESULTS: The behavior science score of the SPP treatment
      group was lower than that of the negative control group (P < 0.01 ) ;
      inflammatory reaction of nasal mucosa in the SPP treatment group were remarkably
      relieved; the number of nasal mucosa mastocyte and mast cell degranulation in the
      SPP treatment group were lower than that of the negative control group (P <0.01
      ). The levels of serum histamine and total IgE in the SPP treatment group were
      lower than that of the negative control group (P <0.01 ). It had no significant
      difference in the positive control group and the SPP treatment group and the
      blank control group (P > 0.05 ). CONCLUSION: Spirulina platensis can prevent and
      treat AR in rats, which implies the possibility of using spirulina platensis for
      AR patients in the future.

PMID- 15871201
TI  - [Uroflowmetry and its influence factors in benign prostate hyperplasia patients].
AB  - OBJECTIVE: To determine the relationship between uroflowmetry and age, the course
      of disease, premicturition volume, transition zone index and proportion of stroma
      to-epithelium in benign prostate hyperplasia (BPH) patients. METHODS: Eighty-nine
      BPH patients in our hospital from 2000 to 2003 were evaluated. With the CMM3
      pathology image analysis system, transrectal ultrasound and Dantec 2000
      urodynamic instrument, the value of influence factors was determined. A linear
      regression was applied to analyze all the data by SPSS software. RESULTS: The
      flow rate was correlated to premicturition volume ( r = 0. 477, P < 0.01) and
      proportion of stroma-to-epithelium significantly ( r = - 0.437, P < 0.05) , but
      was not correlated to the age, the course of disease and transition zone index
      significantly. The parameter of flow rate/premicturition volume had no difference
      in 3 micturitions in all patients. CONCLUSION: The parameter (flow
      rate/premicturition volume)could be used to evaluate the micturition status of
      the BPH patients whose bladder volume is less than 200 ml. We should pay more
      attention to receptor blockers when we treat BPH patients.

PMID- 15871202
TI  - [Progression of RNA interference technology and its application in the research
      of gene function and gene therapy].

PMID- 15871203
TI  - [Renin angiotensin system in local bone marrow].

PMID- 15871205
TI  - [Clinical analysis of cardial tamponade complicating interventional procedures].

PMID- 15871204
TI  - [Construction and expressing assay of eukaryotic-expression plasmid expressing
      extracellular domain of porcine endoglin].

PMID- 15871206
TI  - [Endobronchial tuberculosis treated by local clean-up and antiphthisic drug
      infusion combined with microwave under fiberoptic bronchoscope].

PMID- 15871207
TI  - [Clinical analysis of 79 cases of cervical cancer].

PMID- 15871208
TI  - [Resistant analysis and cultivation results of 3 160 blood specimen].

PMID- 15871209
TI  - Dental mission trips.

PMID- 15871210
TI  - Dental mission trips.

PMID- 15871211
TI  - Military dentists.

PMID- 15871212
TI  - Neighborhood Health Clinics: working in cooperation with Isaac Knapp District
      Dental Society.

PMID- 15871214
TI  - Open access and you.

PMID- 15871213
TI  - Service learning at IUSD: fostering civic responsibility.

PMID- 15871215
TI  - High levels of perchlorate found in U.S. mothers' milk.

PMID- 15871216
TI  - More clues to HBCD isomer mystery.

PMID- 15871217
TI  - Solar cells that harness infrared light.

PMID- 15871218
TI  - Responding to water contamination threats.

PMID- 15871219
TI  - Clarifying the complicated new source review.

PMID- 15871220
TI  - Why is metal bioaccumulation so variable? Biodynamics as a unifying concept.
AB  - Ecological risks from metal contaminants are difficult to document because
      responses differ among species, threats differ among metals, and environmental
      influences are complex. Unifying concepts are needed to bettertie together such
      complexities. Here we suggest that a biologically based conceptualization, the
      biodynamic model, provides the necessary unification for a key aspect in risk:
      metal bioaccumulation (internal exposure). The model is mechanistically based,
      but empirically considers geochemical influences, biological differences, and
      differences among metals. Forecasts from the model agree closely with
      observations from nature, validating its basic assumptions. The biodynamic metal
      bioaccumulation model combines targeted, high-quality geochemical analyses from a
      site of interestwith parametrization of key physiological constants for a species
      from that site. The physiological parameters include metal influx rates from
      water, influx rates from food, rate constants of loss, and growth rates (when
      high). We compiled results from 15 publications that forecast species-specific
      bioaccumulation, and compare the forecasts to bioaccumulation data from the
      field. These data consider concentrations that cover 7 orders of magnitude. They
      include 7 metals and 14 species of animals from 3 phyla and 11 marine, estuarine,
      and freshwater environments. The coefficient of determination (R2) between
      forecasts and independently observed bioaccumulation from the field was 0.98.
      Most forecasts agreed with observations within 2-fold. The agreement suggests
      that the basic assumptions of the biodynamic model are tenable. A unified
      explanation of metal bioaccumulation sets the stage for a realistic understanding
      of toxicity and ecological effects of metals in nature.

PMID- 15871221
TI  - Comparing estimates of persistence and long-range transport potential among
      multimedia models.
AB  - Overall persistence (Pov) and long-range transport potential (LRTP) of organic
      chemicals are environmental hazard metrics calculated with multimedia fate and
      transport models. Since there are several models of this type, it is important to
      know whether and how different model designs (model geometry, selection of
      compartments and processes, process descriptions) affect the results for Pov and
      LRTP. Using a set of 3175 hypothetical chemicals covering a broad range of
      partition coefficients and degradation half-lives, we systematically analyze the
      Pov and LRTP results obtained with nine multimedia models. We have developed
      several methods that make it possible to visualize the model results efficiently
      and to relate differences in model results to mechanistic differences between
      models. Rankings of the hypothetical chemicals according to Pov and LRTP are
      highly correlated among models and are largely determined by the chemical
      properties. Domains of chemical properties in which model differences lead to
      different results are identified, and guidance on model selection is provided for
      model users.

PMID- 15871222
TI  - Comparative advantage: the impact of ISO 14001 environmental certification on
      exports.
AB  - Relative to the enormous acceptance of the ISO 9000 quality standard, the ISO
      14001 environmental management certification has been met with only moderate
      enthusiasm among industrial facilities. The literature on corporate motivation
      for ISO 14001 participation is relatively modest considering the enormous number
      of publications reviewing other aspects of its adoption and implementation. It
      would seem that the present "marketing" package supporting ISO environmental
      commitments does not seem to offer sufficiently persuasive incentives for
      increased sales, either domestically or internationally. While researchers assume
      that a higher export rate of companies is positively associated with higher ISO
      participation rates, there have been very few empirical studies that support this
      inference, and conclusions have not been based on data taken from importing
      countries orfrom a systematic evaluation of expressed corporate preference for
      products sold by ISO 14001 certified companies. The present study reports the
      results of a survey to firms in six countries that are Israel's leading trade
      partners, importing chemicals, textiles, and produce. The survey results confirm
      that while the international market still considers price and quality as the
      paramount factors in selection of suppliers, environmental management systems
      (EMS) are an important feature that is frequently taken into consideration. EMS
      certification appears to signify a supplier who is managing the business well and
      exhibiting ethical responsibility. The European market proved to be more
      environmentally conscious than those in other industrialized parts of the world.
      EMS offer a particularly valuable advantage for producers wishing to reach
      European markets. As policy-makers seek to expand the voluntary adoption of EMS,
      a clear advantage for exporters should be highlighted among national industries.

PMID- 15871223
TI  - Quantification of local and global benefits from air pollution control in Mexico
      City.
AB  - Complex sociopolitical, economic, and geographical realities cause the 20 million
      residents of Mexico City to suffer from some of the worst air pollution
      conditions in the world. Greenhouse gas emissions from the city are also
      substantial, and opportunities for joint local-global air pollution control are
      being sought. Although a plethora of measures to improve local air quality and
      reduce greenhouse gas emissions have been proposed for Mexico City, resources are
      not available for implementation of all proposed controls and thus prioritization
      must occur. Yet policy makers often do not conduct comprehensive quantitative
      analyses to inform these decisions. We reanalyze a subset of currently proposed
      control measures, and derive cost and health benefit estimates that are directly
      comparable. This study illustrates that improved quantitative analysis can change
      implementation prioritization for air pollution and greenhouse gas control
      measures in Mexico City.

PMID- 15871224
TI  - Characterization of humic substances by environmental scanning electron
      microscopy.
AB  - Environmental scanning electron microscopy (ESEM) is a new technique capable of
      imaging micron and submicron particles. Here, we have applied it to image and
      quantify natural aquatic organic matter (standard Suwannee River humic acid,
      SRHA). Uniquely, we have observed the humic aggregate structures as a function of
      humidity and pH. Large aggregates of tens of micrometers were observed as the
      dominant material under all conditions, although much smaller material was also
      observed. Fractal dimensions (D) were calculated between 1.48 and 1.70, although
      these values were not statistically different under conditions of low humidity.
      However, D values calculated at high humidities (85%) during the rehydration
      phase were significantly lower (1.48+/-0.01) than in the initial dehydration
      phase (1.69+/-0.01). This hysteresis indicated that full rehydration of the HS
      was either kinetically slow or irreversible after dehydration. Fractal analysis
      of ESEM images was also performed to probe the change in aggregate structure as a
      function of pH. Minimum values were calculated at neutral pHs, rising by 0.1-0.2
      at both high and low pHs because of a combination of the physical chemistry of HS
      and the impacts of the drying regime within the ESEM. Thus, ESEM was an important
      complementary technique to other analytical methods. At present, ESEM cannot be
      used to image nonperturbed natural samples. However, the method is an ideal
      method for probing the changes in colloid structure as function of hydration
      state and has the potential to perform fully quantitative and nonperturbing
      analysis of colloidal structure.

PMID- 15871225
TI  - Joint sealants: an overlooked diffuse source of polychlorinated biphenyls in
      buildings.
AB  - In October 2000, joint sealants containing polychlorinated biphenyls (PCB) were
      discovered in various public buildings in Switzerland. Triggered by this event, a
      nationwide comprehensive study was initiated by the Swiss Agency for the
      Environment, Forests, and Landscape, and 1348 samples of joint sealants as well
      as 160 indoor air samples from concrete buildings erected between 1950 and 1980
      were analyzed. Out of 1348 samples, 646 (48%) contained PCB. In 279 (21%)
      samples, PCB concentrations of 10 g/kg and more were detected, and concentrations
      of 100 g/kg of PCB or more were found in 129 (9.6%) samples. These data indicate
      that PCB were widely used as plasticizers in joint sealants in Switzerland. In
      buildings constructed between 1966 and 1971, one-third of all joint sealants
      investigated contained more than 10 g/kg of PCB. PCB concentrations exceeding the
      limit of 0.050 g/kg above which material is required to be treated as PCB bulk
      product waste were reached by 568 samples (42%). PCB with a chlorine content
      between 45 and 55%, corresponding to mixtures such as Clophen A50, Aroclor 1248,
      and Aroclor 1254, were encountered in 316 samples (70%). In 42 cases (26%) where
      joint sealants containing PCB were present, clearly elevated PCB indoor air
      concentrations above 1 microg/m3 were encountered. In eight cases (5%), levels
      were higher than 3 microg/m3. The Swiss tentative guideline value of 6 microg/m3
      (based on a daily exposure of 8 h) for PCB in indoor air was exceeded in one case
      (0.6%). On the basis of this work, representing the first large-scale nationwide
      analysis of the issue of PCB-contaminated joint sealants, we estimate that there
      are still 50-150 t of PCB present in these materials, acting as diffuse sources.
      They are distributed over many hundreds of buildings all over the country and
      represent a significant but frequently overlooked inventory of PCB. In light of
      the Stockholm Convention on persistent organic pollutants that entered into force
      last year, reduction of the release of PCB from these widely used materials is an
      important issue to be addressed.

PMID- 15871226
TI  - Microbial catabolic diversity in soils contaminated with hydrocarbons and heavy
      metals.
AB  - Understanding indigenous microbial function in contaminated soil is crucial to
      the successful development and use of bioremediation technologies. We measured
      the catabolic diversity of indigenous microbial communities in soils with a 30-yr
      history of Pb, Cr, and hydrocarbon (HC) contamination using a modified substrate
      induced respiration method. There were characteristic differences of microbial
      respirations in the response of highly versus less contaminated soils to the
      range of organic substrates used. The catabolic response to glucose as compared
      to succinic acid was approximately 1:5 in less contaminated soils, but 1:25 in
      highly contaminated soils. In contrast, the response ratio to glucose versus
      aromatics was about 1:0.4 in less contaminated soils and 1:1 in highly
      contaminated soils. Principal components analysis (PCA) of the responses
      confirmed that catabolic diversity differed between highly and less contaminated
      soils. Univariate analysis also indicated that catabolic diversity was reduced in
      highly contaminated soils. This catabolic difference was strongly associated with
      the alteration of microbial community composition. Statistical analyses suggested
      that the variation in microbial community catabolic diversity was attributed to
      HCs more than to Pb and Cr.

PMID- 15871227
TI  - Occupational exposure to commercial decabromodiphenyl ether in workers
      manufacturing or handling flame-retarded rubber.
AB  - Commercial decabromodiphenyl ether (DecaBDE) is commonly used as a flame
      retardant in different electrical and textile applications. It is also used in
      the production of flame-retarded rubber compound. DecaBDE is the major technical
      polybrominated diphenyl ether (PBDE) in use today and consists mainly of
      decabromodiphenyl ether (BDE-209). PBDEs, including BDE-209, are well-known
      environmental pollutants, ubiquitous both in aquatic and terrestrial
      environments. The aim of the present study was to assess the exposure to PBDEs in
      workers manufacturing or handling rubber which was flame retarded with DecaBDE. A
      referent group, abattoir workers (slaughterhouse workers), with no occupational
      exposure to PBDEs, was also investigated. Moreover, the methodology for analysis
      of PBDEs in serum was refined, with special emphasis on congeners with a high
      number of bromine substituents, i.e., octa- to decaBDEs. The highest BDE-209
      concentration observed among the rubber workers was 280 pmol/g lipid weight
      (I.w.) (270 ng/g I.w.). The median concentration of BDE-209 among rubber workers
      was 37 pmol/g I.w. (35 ng/g I.w.). Among referents, the median was 2.5 (range
      0.92-9.7) pmol/g I.w. (median 2.4 ng/g I.w.). In rubber workers the BDE-209
      concentrations were up to 32% (median 4%) of the 2,2',4,4',5,5'-chlorobiphenyl
      (CB-153) concentrations, on a molar basis, whereas the referents had BDE-209
      concentrations which were similar to that of 2,2',4,4'-bromodiphenyl ether (BDE
      47), below 1.4% (median 0.3%) of the CB-153 concentration. Concentrations of all
      nonabromodiphenyl ethers (nonaBDEs) and several octabrmodiphenyl ethers
      (octaBDEs) congeners, including BDE-203, were also elevated among the rubber
      workers, with 2.5- to 11-fold higher median concentrations, compared to the
      referents. The results confirm a significant uptake of BDE-209 in the workers
      exposed to DecaBDE and indicate a potential for in vivo formation of lower BDEs
      in these persons.

PMID- 15871228
TI  - Hexabromocyclododecane in marine species from the Western Scheldt Estuary:
      diastereoisomer- and enantiomer-specific accumulation.
AB  - Hexabromocyclododecane (HBCD) is a widely used brominated flame retardant, which
      is increasingly reported in the environment. Here, we report on the
      diastereomeric and, for the first time, on the enantiomeric composition of HBCD
      in muscle and liver of several fish species caught in the Western Scheldt Estuary
      (The Netherlands). The total HBCD content (sum of alpha-, beta-, and gamma
      diastereoisomers), as well as the distribution of diastereoisomers and
      enantiomers, varied between the species. The levels of total HBCD (9-1110 ng/g
      lipid weight) found in fish tissues were higher than those measured in fish from
      European rivers with no known point sources of HBCD but lower than in fish
      samples collected near factories producing or using HBCD. The concentrations of
      total HBCD expressed on a lipid weight basis were higher in liver than in muscle
      for bib and whiting, while in sole, HBCD had no preferential distribution between
      the tissues. A similar pattern for liver and muscle distribution was already
      observed for polybrominated diphenyl ethers (PBDEs) in these species. The alpha
      HBCD diastereoisomer was most abundant in all fish samples with a higher
      contribution to the total HBCD levels in liver compared to muscle for bib and
      whiting. The gamma-HBCD diastereoisomer accumulated less in liver than in muscle
      of sole, bib, and whiting. For the first time, enantiomer fractions were
      determined for HBCD diastereoisomers in liver of three fish species and in muscle
      of two fish species. A significant enrichment of the (+) alpha-HBCD enantiomer
      was found in whiting and bib liver samples. A high enantioselectivity has also
      been seen for the gamma-HBCD diastereoisomer in whiting liver.

PMID- 15871229
TI  - Polychlorinated dioxins and furans from the World Trade Center attacks in
      exterior window films from lower Manhattan in New York City.
AB  - Samples of ambient organic films deposited on exterior window surfaces from lower
      Manhattan and Brooklyn in New York City were collected six weeks after the
      terrorist attacks at the World Trade Center (WTC) on September 11, 2001 and
      analyzed for polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). Total
      tetra- through octa-CDD/F concentrations in window films within 1 km of the WTC
      site in lower Manhattan ranged up to 630,000 pg/m2 (estimated as a mass
      concentration of ca. 1,300,000 pg/ g) and a maximum toxic equivalent (TEQ)
      concentration of 4700 TEQ/m2 (ca. 10 000 pg TEQ/g). Measurements at a background
      site 3.5 km away in Brooklyn showed lower concentrations at 130 pg TEQ/m2 (260 pg
      TEQ/g). Ambient gas-phase PCDD/F concentrations estimated for each site using an
      equilibrium partitioning model suggested concentrations ranging from ca. 2700 fg
      TEQ/m3 near the WTC site to the more typical urban concentration of 20 fg-TEQ/m3
      atthe Brooklyn site. Multivariate analyses of 2,3,7,8-substitued congeners and
      homologue group profiles suggested unique patterns in films near the WTC site
      compared to that observed at background sites in the study area and in other
      literature-derived combustion source profiles. Homologue profiles near the WTC
      site were dominated by tetra-, penta-, and Hexa-CDD/Fs, and 2,3,7,8-substituted
      profiles contained mostly octa- and hexachlorinated congeners. In comparison,
      profiles in Brooklyn and near mid-Manhattan exhibited congener and homologue
      patterns comprised mainly of hepta- and octa-CDDs, similar to that commonly
      reported in background air and soil.

PMID- 15871230
TI  - Climate dependency of tree growth suppressed by acid deposition effects on soils
      in northwest Russia.
AB  - Increased tree growth in temperate and boreal forests has been proposed as a
      direct consequence of a warming climate. Acid deposition effects on nutrient
      availability may influence the climate dependency of tree growth, however. This
      study presents an analysis of archived soil samples that has enabled changes in
      soil chemistry to be tracked with patterns of tree growth through the 20th
      century. Soil samples collected in 1926, 1964, and 2001, near St. Petersburg,
      Russia, showed that acid deposition was likely to have decreased root-available
      concentrations of Ca (an essential element) and increased root-available
      concentrations of Al (an inhibitor of Ca uptake). These soil changes coincided
      with decreased diameter growth and a suppression of climate-tree growth
      relationships in Norway spruce. Expected increases in tree growth from climate
      warming may be limited by decreased soil fertility in regions of northern and
      eastern Europe, and eastern North America, where Ca availability has been reduced
      by acidic deposition.

PMID- 15871231
TI  - Perchlorate and iodide in dairy and breast milk.
AB  - Perchlorate inhibits iodide uptake and may impair thyroid and neurodevelopment in
      infants. Recently, we unambiguously identified the presence of perchlorate in all
      seven brands of dairy milk randomly purchased from grocery stores in Lubbock, TX.
      How widespread is perchlorate in milk? Perchlorate in 47 dairy milk samples from
      11 states and in 36 human milk samples from 18 states were measured. Iodide was
      also measured in a number of the samples. Perchlorate was detectable in 81 of 82
      samples. The dairy and breast milk means were, respectively, 2.0 and 10.5
      microg/L with the corresponding maximum values of 11 and 92 microg/L. Perchlorate
      is present in virtually all milk samples, the average concentration in breast
      milk is five times higher than in dairy milk. Although the number of available
      measurements are few at this point, for breast milk samples with a perchlorate
      content greater than 10 microg/L, the iodide content is linearly correlated with
      the inverse of the perchlorate concentration with a r2 of >0.9 (n = 6). The
      presence of perchlorate in the milk lowers the iodide content and may impair
      thyroid development in infants. On the basis of limited available data, iodide
      levels in breast milk may be significantly lower than it was two decades ago.
      Recommended iodine intake by pregnant and lactating women may need to be revised
      upward.

PMID- 15871232
TI  - Lead isotopic composition of fly ash and flue gas residues from municipal solid
      waste combustors in France: implications for atmospheric lead source tracing.
AB  - Fly ash and flue gas residues from eight municipal solid waste combustors (MSWC)
      in France (1992--93 and 1998/ 2002) were analyzed for their Pb isotopic
      composition. Fly ashes are more representative of solid residual particles,
      whereas flue gas residues reflect mostly the composition of gas phases. Both
      sample types contain hundreds to thousands of micrograms of metals per gram.
      Leaching experiments showed that metals are present in condensed phases, probably
      as sulfates and chlorides, and suggest that Cd, Pb, and Zn are highly
      fractionated from one another during volatilization/condensation processes
      occurring during combustion. Although all the samples analyzed define a fairly
      restricted range in Pb isotopic compositions (206Pb/207Pb = 1.148-1.158 and
      208Pb/206Pb = 2.101-2.114) compared to other environmental samples, some MSWC
      produce materials having distinct isotopic compositions, whereas others display
      very similar ones. Isotopic heterogeneity is also measured between samples from a
      single MSWC. This is interpreted as resulting from the heterogeneity of the waste
      source materials. The range of Pb isotopic composition of incinerator materials
      form a well-defined linear array in the 208Pb/206Pb versus 206Pb/207Pb diagram.
      This array is compatible with the previously reported European standard pollution
      (ESP) line and most probably represent the average lead isotopic composition of
      industrial atmospheric emissions in France, with the following ratios:
      206Pb/207Pb = 1.154+/-0.003 and 208Pb/206Pb = 2.107+/-0.003 (1sigma).

PMID- 15871233
TI  - Adsorption of 4-picoline and piperidine to the hydrated SiO2 surface: probing the
      surface acidity with vibrational sum frequency generation spectroscopy.
AB  - Vapor adsorption is an important process influencing the migration and the fate
      of many organic pollutants in the environment. In this study, vibrational sum
      frequency generation (SFG) spectroscopy was used to study the adsorption of two
      surface acidity probe molecules, 4-picoline (pKa = 5.94) and piperidine (pKa =
      11.24), onto the amorphous SiO2 surface. The adsorption of 4-picoline onto the
      silica surface occurs by forming weak hydrogen bonds between the nitrogen atoms
      of 4-picoline molecules and the hydrogen atoms of surface silanol OH groups.
      Piperidine molecules are strongly chemisorbed onto the SiO2 surface through the
      protonation of piperidine molecules by surface silanol OH groups. The SFG results
      indicate that the surface acidity constant of silanol OH groups (pKa-(HOSi triple
      bond)) is in the range of 5.94-11.24 at the air/solid interface. Although this
      range of surface acidity constants is quite wide, it is possible to narrow it by
      choosing probe molecules with a smaller pKa range. Together with theoretical
      prediction methods, adsorption studies using vibrational SFG spectroscopy are
      capable of quantifying the surface acidity of mineral oxides by carefully
      choosing the acidity probe molecules.

PMID- 15871234
TI  - Characterization of aromatic compound sorptive interactions with black carbon
      (charcoal) assisted by graphite as a model.
AB  - Molecular interactions controlling the sorption of pollutants to environmental
      black carbons (soot, charcoal) are not well-resolved. Sorption of a series of
      aromatic compounds was studied to wood charcoal and nonporous graphite powder as
      a model adsorbent. Issues of concern were the possible involvement of pi-pi
      electron donor-acceptor (EDA) interactions of electron-poor and electron-rich
      solutes with the graphene (polycyclic aromatic) surface and size exclusion
      effects. Sorption of pi-acceptors, benzonitrile (BNTL), 4-nitrotoluene (MNT), 2,4
      dinitrotoluene (DNT), and 2,4,6-trinitrotoluene (TNT), and to a lesser extent pi
      donor solutes, naphthalene (NAPH) and phenanthrene (PHEN), was greater than
      predicted by hydrophobic driving forces in accord with their acceptor or donor
      strength. Hydrophobic effects were estimated using a concentration-dependent free
      energy relationship between adsorption and partitioning into an inert solvent (n
      hexadecane or benzene) for a non-donor/non-acceptor calibration set (benzene and
      chlorinated and methylated benzenes). Molecular complexation between acceptors
      and model graphene donors, NAPH, PHEN, and pyrene (PYR), in chloroform and
      benzene was tracked by ring-current induced upfield shifts in the 1H NMR spectrum
      and by charge-transfer bands in the UV/visible spectrum. The EDA component of
      graphite-water adsorption for the acceptors correlated with the NMR-determined
      complexation constant with the model donors in chloroform, which, in turn,
      correlated with pi-acceptor strength (TNT > DNT > MNT > BNTL) and pi-donor
      strength (PYR > PHEN > NAPH). Charcoal-graphite isotherms calculated from
      charcoal-water and graphite-water isotherms indicated molecular sieving effects
      on charcoal for tetrasubstituted benzenes (tetramethylbenzenes and TNT) and some
      trisubstituted benzenes (1,3,5-trichlorobenzene, possibly DNT). When steric
      effects are taken into account, the order in adsorption among acceptors was
      qualitatively similar for graphite and charcoal. The results suggest pi-pi EDA
      interactions of the acceptors-and possibly donors, although the calibration set
      may underestimate the hydrophobic effect for fused ring systems-with both
      graphite and charcoal surfaces. For graphite, it is postulated that pi-acceptors
      interact with electron-rich regions of the basal plane near edges and defects and
      that pi-donors interact with electron-depleted regions further away. A similar
      mechanism may operate on the charcoal but would be modified by the (mostly)
      electron-withdrawing effects of 0 functionality on the edges of graphene sheets.

PMID- 15871235
TI  - Ligand arsenic complexation and immunoperoxidase detection of metallothionein in
      the earthworm Lumbricus rubellus inhabiting arsenic-rich soil.
AB  - Although earthworms have been found to inhabit arsenic-rich soils in the U.K.,
      the mode of arsenic detoxification is currently unknown. Biochemical analyses and
      subcellular localization studies have indicated that As3+-thiol complexes may be
      involved; however, it is not known whether arsenic is capable of inducing the
      expression of metallothionein (MT) in earthworms. The specific aims of this paper
      were (a) to detect and gain an atomic characterization of ligand complexing by X
      ray absorption spectrometry (XAS), and (b) to employ a polyclonal antibody raised
      against an earthworm MT isoform (w-MT2) to detect and localize the metalloprotein
      by immunoperoxidase histochemistry in the tissues of earthworms sampled from
      arsenic-rich soil. Data suggested that the proportion of arsenate to sulfur-bound
      species varies within specific earthworm tissues. Although some arsenic appeared
      to be in the form of arsenobetaine, the arsenic within the chlorogogenous tissue
      was predominantly coordinated with S in the form of -SH groups. This suggests the
      presence of an As::MT complex. Indeed, MT was detectable with a distinctly
      localized tissue and cellular distribution. While MT was not detectable in the
      surface epithelium or in the body wall musculature, immunoperoxidase
      histochemistry identified the presence of MT in chloragocytes around blood
      vessels, within the typhlosolar fold, and in the peri-intestinal region. Focal
      immunostaining was also detectable in a cohort of cells in the intestinal wall.
      The results of this study support the hypothesis that arsenic induces MT
      expression and is sequestered by the metalloprotein in certain target cells and
      tissues.

PMID- 15871236
TI  - Confocal micrometer-scale X-ray fluorescence and X-ray absorption fine structure
      studies of uranium speciation in a tertiary sediment from a waste disposal
      natural analogue site.
AB  - Investigations by micrometer-scale X-ray fluorescence and X-ray absorption fine
      structure (micro-XRF and micro-XAFS) recorded in a confocal geometry on a bore
      core section of a uranium-rich tertiary sediment are performed in order to assess
      mechanisms leading to immobilization of the uranium during diagenesis. Results
      show uranium to be present as a tetravalent phosphate and that U(IV) is
      associated with As(V). Arsenic present is either As(V) or As(O); we found no
      evidence for As(III). The As(O) is observed to be intimately associated with the
      surface of Fe(II) nodules and likely arsenopyrite. A hypothesis for the mechanism
      of uranium immobilization is proposed, where arsenopyrite acted as reductant of
      groundwater-dissolved U(VI), leading to precipitation of less soluble U(IV) and
      thereby forming As(V).

PMID- 15871237
TI  - Reoxidation of reduced uranium with iron(III) (hydr)oxides under sulfate-reducing
      conditions.
AB  - In cultures of Desulfovibrio desulfuricans 620 the effects of iron(III)
      (hydr)oxides (hematite, goethite, and ferrihydrite) on microbial reduction and
      reoxidation of uranium (U) were evaluated under lactate-limited sulfate-reducing
      conditions. With lactate present, G20 reduced U(VI) in both 1,4
      piperazinediethanesulfonate (PIPES) and bicarbonate buffer. Once lactate was
      depleted, however, microbially reduced U served as an electron donor to reduce
      Fe(III) present in iron(III) (hydr)oxides. With the same initial amount of
      Fe(III) (10 mmol/L) for each iron(III) (hydr)oxide, reoxidation of U(IV) was
      greater with hematite than with goethite orferrihydrite. As the initial mass
      loading of hematite increased from 0 to 20 mmol of Fe(III)/L, the rate and extent
      of U(IV) reoxidation increased. Subsequent addition of hematite [15 mmol of
      Fe(III)/L] to stationary-phase cultures containing microbially reduced U(IV) also
      resulted in rapid reoxidation to U(VI). Analysis by U L3-edge X-ray absorption
      near-edge spectroscopy (XANES) of microbially reduced U particles yielded spectra
      similar to that of natural uraninite. Observations by high-resolution
      transmission electron microscopy, selected area electron diffraction, and energy
      dispersive X-ray spectroscopic analysis confirmed that precipitated U associated
      with cells was uraninite with particle diameters of 3-5 nm. By the same
      techniques, iron sulfide precipitates were found to have a variable Fe and S
      stoichiometry and were not associated with cells.

PMID- 15871238
TI  - Toward a biotic ligand model for freshwater green algae: surface-bound and
      internal copper are better predictors of toxicity than free Cu2+-ion activity
      when pH is varied.
AB  - The freshwater green microalgae Chlorella sp. and Pseudokirchneriella subcapitata
      (P. subcapitata) were chronically (48 and 72 h, respectively) exposed to copper
      at various pH levels, i.e., pH 6-7.5 and pH 5.9-8.5, respectively. Concentrations
      resulting in 50% inhibition of exponential growth rate (EC50) were determined as
      dissolved Cu, estimated chemical activity of the free Cu2+ ion (as pCu = -
      log{Cu2+ activity as molarity}), and as external (surface-bound) Cu and internal
      Cu in the algal cells. With increasing pH, EC50dissolved decreased from 30 to 1.1
      microg of Cu L(-1) for Chlorella sp. and from 46 to 18 microg of Cu L(-1) for P.
      subcapitata. The pH effect on copper toxicity was even more obvious when
      expressed as Cu2+ activity. The EC50pCu increased on average 1.4 pCu unit per pH
      unit for Chlorella sp. and 1.1 pCu unit per pH unit for P. subcapitata, thus
      indicating a marked increase of Cu2+ toxicity at higher pH (more than 1 order of
      magnitude per pH unit). In contrast, it was found that EC50 values expressed as
      surface bound or external copper (EC50external) and as internal copper
      (EC50internal) did not vary substantially when pH was increased. External Cu was
      operationally defined as the Cu fraction removable from the algal cell by short
      term contact with ethylenediaminetetraacetic acid; internal copper was defined as
      the nonremovable fraction. For Chlorella sp. the EC50external varied between 5
      and 10 fg of Cu/ cell (factor of 2 difference) and the EC50internal between 25
      and 40 fg of Cu/cell (factor of 1.6 difference). For P. subcapitata the
      EC50external varied between 10 and 28 fg of Cu/cell (factor of 2.8 difference)
      and the EC50internal between 42 and 71 fg of Cu/cell (factor of 1.7 difference).
      Because the observed variation in EC50external and EC50internal is much less than
      the variation in EC50Cu2+, it is concluded that both external and internal copper
      are better predictors of copper toxicity than Cu2+ when pH is varied. From the
      perspective of toxicity modeling, this observation is the first step toward
      considering the use of the cell surface as the algal biotic ligand for Cu in a
      similar way as fish gills fulfill this role in the biotic ligand model for
      predicting metal toxicity to fish species.

PMID- 15871239
TI  - Oxidation of nanomolar levels of Fe(II) with oxygen in natural waters.
AB  - The oxidation of Fe(II) by molecular oxygen at nanomolar levels has been studied
      using a UV-Vis spectrophotometric system equipped with a long liquid waveguide
      capillary flow cell. The effect of pH (6.5-8.2), NaHCO3 (0.1-9 mM), temperature
      (3-35 degrees C), and salinity (0-36) on the oxidation of Fe(II) are presented.
      The first-order oxidation rates at nanomolar Fe(II) are higher than the values at
      micromolar levels at a pH below 7.5 and lower than the values at a higher pH. A
      kinetic model has been developed to consider the mechanism of the Fe(II)
      oxidation and the speciation of Fe(II) in seawater, the interactions between the
      major ions, and the oxidation rates of the different Fe(II) species. The
      concentration of Fe(II) is largely controlled by oxidation with O2 and O2.- but
      is also affected by hydrogen peroxide that may be both initially present and
      formed from the oxidation of Fe(II) by superoxide. The model has been applied to
      describe the effect of pH, concentration of NaHCO3, temperature, and salinity on
      the kinetics of Fe(II) oxidation. At a pH over 7.2, Fe(OH)2 is the most important
      contributing species to the apparent oxidation rate. At high levels of CO3(2-)
      and pH, the Fe(CO3)2(2-) species become important. At pH values below 7, the
      oxidation rate is controlled by Fe2+. Using the model, log k(i) values for the
      most kinetically active species (Fe2+, Fe(OH)+, Fe(OH)2, Fe(CO3), and Fe(CO3)2(2
      )) are given that are valid over a wide range of temperature, salinity, and pH in
      natural waters. Model results showthatwhen H2O2 concentrations approach the
      Fe(II) concentrations used in this study, the oxidation of Fe(II) with H2O2 also
      needs to be considered.

PMID- 15871241
TI  - Catalysis of elemental sulfur nanoparticles on chromium(VI) reduction by sulfide
      under anaerobic conditions.
AB  - Chromate (CrVI) reduction by sulfide was conducted in anaerobic batch
      experimental systems. The molar ratio of the reduced CrVI to the oxidized S(-II)
      was 1:1.5 during the reaction, suggesting that the product of sulfide oxidation
      was elemental sulfur. Under the anaerobic condition, the reaction was pseudo
      first order initially with respect to CrVI, but the rate was dramatically
      accelerated at the later stage of the reaction. The rate acceleration was due to
      catalysis by elemental sulfur nanoparticles; dissolved species such as monomeric
      elemental sulfur and polysulfides appeared to be ineffective catalysts. Elemental
      sulfur nanoparticles were capable of adsorbing sulfide and such adsorbed sulfide
      exhibited much higher reactivity toward CrVI reduction than the aqueous-phase
      sulfide, resulting in the observed rate acceleration. Kinetic data under various
      reactant concentrations can be represented by the following empirical kinetic
      equation: -d[CrVI]/dt = k1 [CrVI][H2S]0.63 + k3[CrVI][triple bond S--SH]0.57. The
      first term on the right-hand side corresponds to the noncatalytic pathway, with
      k1 = 1.0 x 10(-3) (microM)(-0.63) min(-1) at pH 7.60 and 8.2 x 10(-5) (microM)
      0.63 min(-1) at pH 8.10. The second term, k3[CrVI][triple bond S--SH]b, is the
      catalytic term with [triple bond S--SH] representing the adsorbed concentration
      of sulfide on the elemental sulfur nanoparticles (microM). The catalytic term is
      more important at the later stage of the reaction, as indicated by the observed
      kinetics and the enhancement of the reaction rate by externally added elemental
      sulfur nanoparticles. At pH 8.10, k3 = 0.0057 (microM)(-0.57) min(-1).

PMID- 15871240
TI  - Root-induced cycling of lead in salt marsh sediments.
AB  - A gold-mercury amalgam microelectrode was used in situ to measure Pb(II) by
      anodic stripping voltammetry and O2, Fe(II), Mn(II), and HS- by square-wave
      voltammetry in sediment pore water in a Haliomione portulacoides stand in a Tagus
      estuary salt marsh. The measurements were made in spring, summer, and fall, and
      were supplemented with analysis of Pb in solid phases and stable isotope analysis
      of Pb. In spring, the pore water was anoxic, Fe(II) reached concentrations as
      high as 1700 micromol/L, and Pb(II) was undetectable (<0.1 micromol/L). However,
      in summer, the pore water was oxic, Fe(II) was undetectable, and Pb(II) was
      present throughout the 20 cm deep root zone in concentrations reaching 6
      micromol/L. In fall, low levels of O2 and Pb(II) were detected in the upper half
      of the root zone, and low concentrations of Fe(II) were detected in the lower
      half. The annual cycle of Pb is controlled by the growth and decay of roots.
      Roots deliver oxygen, which oxidizes lead-bearing solid phases and releases
      Pb(II) to the sediment pore water. Iron oxides, which form in the rhizosphere
      when Fe(II) is oxidized, are apparently not efficient sorbents for Pb(II) under
      the organic-rich conditions in this sediment. This allows Pb(II) to remain
      soluble and available for uptake by the roots. In fall and winter,when roots
      decay and the oxygen flux to the sediment stops, Pb is released from the decaying
      roots and returned to and precipitated in the anoxic sediment, likely as a
      sulfide. On an annual basis more than 20% of the total mass of Pb in the root
      zone cycles between root tissue and inorganic sediment phases. Depending on
      location, anthropogenic Pb constitutes 30-90% of total Pb in Tagus Estuary salt
      marshes.

PMID- 15871243
TI  - UV photolytic mechanism of N-nitrosodimethylamine in water: dual pathways to
      methylamine versus dimethylamine.
AB  - The direct ultraviolet (UV) photolysis of N-nitrosodimethyl-amine (NDMA), a well
      known potential carcinogen, was investigated in aqueous solution with its
      degradation products analyzed quantitatively. NDMA is known to be photolyzed
      either to dimethylamine (DMA) or to methylamine (MA) by two distinct pathways.
      However, the mechanism through which NDMA is photolyzed to DMA is still not
      clearly understood. This study reveals a new mechanistic pathway of NDMA
      photolysis to DMA by identifying the factors influencing the photolysis pathway.
      The two pathways of NDMA photolysis were found to be strongly dependent on the
      initial NDMA concentration and solution pH. Increasing the initial NDMA
      concentration clearly favored the DMA formation path. DMA production was
      optimized in the region of pH 4-5. The nitrite ion (NO2-) produced from the NDMA
      photolysis was identified as a key reagent in directing the NDMA photolysis
      toward DMA production. The observed photolytic behaviors of NDMA photolysis could
      be successfully explained in terms of the new mechanism involving the role of NO2
      .

PMID- 15871242
TI  - Levels of hexabromocyclododecane in harbor porpoises and common dolphins from
      western European seas, with evidence for stereoisomer-specific biotransformation
      by cytochrome p450.
AB  - Commercial hexabromocyclododecane (HBCD) is a high-production-volume flame
      retardant applied in polystyrene foams. It contains three stereoisomers, of which
      gamma-HBCD always dominates. Here we report on the levels of HBCD in blubber of
      harbor porpoise and common dolphin from different European seas. The highest
      total (sigma)-HBCD levels were measured in harbor porpoises stranded on the Irish
      and Scottish coasts of the Irish Sea (median concentration 2.9 microg (g of
      lipid)(-1)) and the northwest coast of Scotland (median concentration 5.1 microg
      (g of lipid)(-1)). The median levels in other areas were, for the harbor porpoise
      south coast of Ireland, 1.2 microg (g of lipid)(-1), for the coasts of The
      Netherlands, Belgium, and France north of Calais (southern North Sea), 1.1 microg
      (g of lipid)(-1), for the east coast of Scotland (northern North Sea), 0.77
      microg (g of lipid)(-1), and, for Galicia (Spain), 0.1 microg (g of lipid)(-1).
      The median levels for the common dolphin were, for west coast of Ireland, 0.9
      microg (g of lipid)(-1), for the French coast of the English Channel between
      Normandy and Brest, 0.4 microg (g of lipid)(-1), and, for Galicia, 0.2 microg (g
      of lipid)(-1). A subset of 10 harbor porpoise and 9 common dolphin blubber
      samples representing all areas were analyzed by LC/MS to determine the
      diastereomeric composition of their HBCD residues. All samples showed exclusively
      the peak of alpha-HBCD. To test if biotransformation by the cytochrome P450
      system could explain the observed compositional difference with technical HBCD
      mixtures, a number of in vitro assays with microsomal preparations of liver were
      carried out. We had to revert to material stored at -80 degrees C from laboratory
      rats and a fresh harbor seal found dead in the Dutch Wadden Sea, since such liver
      samples of cetaceans were not in our possession. The in vitro assays showed that
      beta- and gamma-HBCDs were indeed significantly metabolized when incubated in the
      presence of NADPH as electron donor, compared to a set of reference samples which
      were identical except for the addition of NADPH. In contrast, the peak of alpha
      HBCD did not decrease significantly in the presence of NADPH. In separate
      microsomal assays with beta- and gamma-HBCDs, new peaks of brominated compounds
      (signal at m/z = 79 or 81) with masses of [M + 0] were formed only when NADPH was
      added. This confirms the process of cytochrome P450 mediated biotransformation.
      Although rat and harbor seal belong to different families of the mammalia than
      the cetaceans, we propose that biotransformation by the cytochrome P450 system is
      also the most likely process to explain the exclusive accumulation of alpha-HBCD
      in harbor porpoise and common dolphin.

PMID- 15871245
TI  - Isomer-selective adsorption of amino acids by components of natural sediments.
AB  - We present evidence that under circumstances of low pH and organic-free surfaces
      an ordinary estuarine sediment can exhibit strong optical isomer selectivity in
      its absorption of a number of amino acids. This selectivity can also be seen to a
      lesser degree in the minerals quartz, montmorillonite, and kaolin. Adsorption
      reactions were performed with racemic amino acid mixtures, and after equilibrium,
      deviations from a D/L ratio of 1 were measured and in many cases were found to be
      significant. This was particularly pronounced at pH 4.0, where selective removal
      of the L isomers by adsorption onto sedimentfractions was almosttotal. Changes in
      both the nature and degree of selectivity were also observable in different
      sediment size fractions. While we are at this stage unable to identify the mode
      of primary selectivity, adsorption experiments with these candidate sediment
      components, quartz, kaolin, and montmorillonite do exhibit some selective
      behavior. We believe that the existence of natural chirally selective components
      in sediment may indicate a new approach to the development of chiral catalysis
      and synthesis.

PMID- 15871244
TI  - Pu(V)O2+ adsorption and reduction by synthetic hematite and goethite.
AB  - Changes in aqueous- and solid-phase plutonium oxidation state were monitored over
      time in hematite (alpha-Fe2O3) and goethite (alpha-FeOOH) suspensions containing
      239Pu(V)-amended 0.01 M NaCl. Solid-phase oxidation state distribution was
      quantified by leaching plutonium into the aqueous phase and applying an
      ultrafiltration/solvent extraction technique. The technique was verified using
      oxidation state analogues of plutonium and sediment-free controls of known Pu
      oxidation state. Batch kinetic experiments were conducted at hematite and
      goethite concentrations between 10 and 500 m2 L(-1) in the pH range of 3-8.
      Surface-mediated reduction of Pu(V) was observed for both minerals at pH values
      of 4.5 and greater. At pH 3 no adsorption of Pu(V) was observed on either
      goethite or hematite; consequently, no reduction was observed. For hematite,
      adsorption of Pu(V) was the rate-limiting step in the adsorption/reduction
      process. In the pH range of 5-8, the overall removal of Pu(V) from the system
      (solid and aqueous phases) was found to be approximately second order with
      respect to hematite concentration and of order -0.39 with respect to the hydrogen
      ion concentration. The overall reaction rate constant (k(rxn)), including both
      adsorption and reduction of Pu(V), was 1.75+/-2.05 x 10(-10) (m(-2) L)(-2.08)
      (mol(-1) L)(-0.39) (s(-1)). In contrast to hematite, Pu(V) adsorption to goethite
      occurred rapidly relative to reduction. At a given pH,the reduction rate was
      approximately independent of the goethite concentration, although the hydrogen
      ion concentration (pH) had only a slight effect on the overall reaction rate. For
      goethite, the overall reaction rates at pH 5 and pH 8 were 6.0 x 10(-5) and 1.5 x
      10(-4) s(-1), respectively. For hematite, the reaction rate increased by 3 orders
      of magnitude across the same pH range.

PMID- 15871246
TI  - Methyl arsenic adsorption and desorption behavior on iron oxides.
AB  - In virtually all Earth surface environments, methylated forms of arsenic can be
      found. Because of the widespread distribution and toxicity of methyl-arsenic
      compounds, their adsorption by soil minerals is of considerable interest. The
      objective of this study was to compare the adsorption and desorption behavior of
      methylarsonic acid (MMAsV), methylarsonous acid (MMAsIII), dimethylarsinic acid
      (DMAsV), dimethylarsinous acid (DMAsIII), arsenate (iAsV), and arsenite (iAsIII)
      on iron oxide minerals (goethite and 2-line ferrihydrite) by means of adsorption
      isotherms, adsorption envelopes, and desorption envelopes (using sulfate and
      phosphate as desorbing ligands). MMAsIII and DMAsIII were not appreciably
      retained by goethite or ferrihydrite within the pH range of 3 to 11, while iAsIII
      was strongly adsorbed to both iron oxides. MMAsV and iAsV were adsorbed in higher
      amounts than DMAsV on goethite and ferrihydrite at all pH values studied. MMAsV
      and iAsV exhibited high adsorption affinities on both goethite and ferrihydrite
      from pH 3 to 10, while DMAsV was adsorbed only at pH values below 8 by
      ferrihydrite and below 7 by goethite. All arsenic compounds were desorbed more
      efficiently by phosphate than sulfate. MMAsV, iAsV, and DMAsV each exhibited
      adsorption characteristics suggesting specific adsorption on both goethite and
      ferrihydrite. Increased methyl substitution resulted in both decreased adsorbed
      arsenic at low arsenic concentrations in solution and increased ease of arsenic
      release from the iron oxide surface.

PMID- 15871247
TI  - Mechanisms of dioxin formation from the high-temperature oxidation of 2
      bromophenol.
AB  - The homogeneous, gas-phase oxidative thermal degradation of 2-bromophenol was
      studied in a 1 cm i.d., fused silica flow reactor at a concentration of 88 ppm,
      reaction time of 2.0 s, over a temperature range from 300 to 1000 degrees C.
      Observed products in order of yield were dibenzo-p-dioxin (DD) > 4,6
      dibromodibenzofuran (4,6-DBDF) > 4-monobromodibenzofuran (4-MCDF), dibenzofuran
      (DF), 1-monobromodibenzo-p-dioxin (1-MBDD), naphthalene, bromonaphthalene, 2,4
      dibromophenol, 2,6-dibromophenol, phenol, bromobenzene, and benzene. This result
      is in contrast to the oxidation of 2-chlorophenol, where the major product is 4,6
      dichlorodibenzofuran (4,6-DCDF). 4,6-DBDF was observed in high yields in
      contrastto our previous results for the pyrolysis of 2-bromophenol, where 4,6
      DBDF was not detected. The increase in 4,6-DBDF yields is attributed to hydroxyl
      radical being the major chain carrier under oxidative conditions, which favors
      hydrogen-abstraction reactions that lead to formation of 4,6-DBDF. However, DD is
      still the highest yield product under oxidative conditions because of the
      relative ease of displacement of Br in the ring-closure reaction.

PMID- 15871248
TI  - Uptake, metabolism, accumulation and toxicity of cyanide in Willow trees.
AB  - Chemicals taken up into plants may be accumulated so leading to toxic effects.
      Uptake and phytotoxicity of free cyanide was determined with the willow-tree
      transpiration test. Willow sets were grown in sand and irrigated with varying
      levels of cyanide (CN). Toxicity was determined by measuring transpiration. At CN
      concentrations below 10 mg/L, no toxic effects were observed. At 20 mg/L,
      transpiration was reduced to approximately 50% after 96 h. With 30, 40 and 50
      mg/L, the transpiration decreased with a similar rate to < 20% of the initial
      transpiration within 96 h. Accumulation of cyanide in plant tissue was observed
      at 40 and 50 mg/L. The kinetics of metabolism of cyanide by roots, stems and
      leaves of willows was determined by the closed-bottle metabolism test. The
      Michaelis-Menten parameters v(max) and K(M)(maximal metabolic velocity and half
      saturation constant, respectively) were determined by nonlinear regression.
      Estimates of uptake and metabolism were balanced using a nonlinear mathematical
      model. The model predicted that at low doses (<10 mg/L), the cyanide would be
      rapidly metabolized. At higher doses, uptake would be faster than metabolism and
      consequently cyanide would accumulate in the plant tissue. This relation between
      external dose and internal accumulation is nonlinear and explains the toxic
      effects observed.

PMID- 15871249
TI  - Time-dependent sorption-desorption behavior of 2,4-dichlorophenol and its
      polymerization products in surface soils.
AB  - Contact time-dependent sorption-desorption of 2,4-dichlorophenol (DCP) and DCP
      polymerization products (DPP) was investigated in the context of agricultural and
      woodland soils. DPP was generated in soil slurry reactors by the addition of H2O2
      to solutions containing horseradish peroxidase (HRP) and DCP. Size-exclusion
      chromatography confirmed the formation of oligomeric products including dimers,
      trimers, and tetramers. DCP removal from HRP-amended, soil-free solutions
      occurred as a result of DPP formation and sorption of DCP to the oligomeric
      precipitate. In reactors containing soil particles, additional removal occurred
      due to sorption of residual DCP and DPP to the soil. Sorption of DCP and DPP to
      the surface soils was rapid and appeared to be complete within 1 day. DPP sorbed
      to a greater extent than DCP, especially at higher solute concentrations. Water
      extraction data indicated that while sorbed DCP was readily released into
      solution, sorbed DPP was more resistant to desorption. Both DCP and DPP were more
      readily extracted from the woodland soil than the agricultural soil. Solute
      extractability decreased with contact time, indicating that sorbent-solute
      interactions proceeded long after apparent sorption equilibrium at the particle
      or aggregate scale. Results from this study show that "slow" sorption processes
      occurring at the molecular scale continue long after apparent sorption
      equilibrium at the particle scale. This "aging effect" was operational over
      longer periods for DPP than the parent DCP, thereby ensuring long-term reductions
      in contaminant mobility in soils treated with peroxidase enzyme.

PMID- 15871250
TI  - XANES investigation of phosphate sorption in single and binary systems of iron
      and aluminum oxide minerals.
AB  - Phosphate sorption on Fe- and Al-oxide minerals helps regulate the solubility and
      mobility of P in the environment. The objective of this study was to characterize
      phosphate adsorption and precipitation in single and binary systems of Fe- and Al
      oxide minerals. Varying concentrations of phosphate were reacted for 42 h in
      aqueous suspensions containing goethite, ferrihydrite, boehmite, or
      noncrystalline (non-xl) Al-hydroxide, and in 1:1 (by mass) mixed-mineral
      suspensions of goethite/boehmite and ferrihydrite/ non-xl Al-hydroxide at pH 6
      and 22 degrees C. X-ray absorption near edge structure (XANES) spectroscopy was
      used to detect precipitated phosphate and distinguish PO4 associated with Fe(III)
      versus Al(III) in mixed-mineral systems. Changes in the full width at half
      maximum height (fwhm) in the white-line peak in P K-XANES spectra provided
      evidence for precipitation in Al-oxide single-mineral systems, but not in
      goethite or ferrihydrite systems. Similarly, adsorption isotherms and XANES data
      showed evidence for precipitation in goethite/boehmite mixtures, suggesting that
      mineral interactive effects on PO4 sorption were minimal. However, sorption in
      ferrihydrite/non-xl Al-hydroxide systems and a lack of XANES evidence for
      precipitation indicated that mineral interactions inhibited precipitation in
      these binary mixtures.

PMID- 15871251
TI  - Determination of stability constants of U(VI)-Fe(III)-citrate complexes.
AB  - Ion-exchange experiments were performed to evaluate the formation of the uranium
      citrate and uranium-iron-citrate complexes over a wide concentration range; i.e.,
      environmentally relevant concentrations (e.g., 10(-6) M in metal and ligand) and
      concentrations useful for spectroscopic investigations (e.g., 10(-4) M in metal
      and ligand). The stability of the well-known uranium-citrate complex was
      determined to validate the computational and experimental methods applied to the
      more complex system. Values of the conditional stability constants for these
      species were obtained using a chemical equilibrium model in FITEQL. At a pH of
      4.0, the stability constant for uranium-citrate complex (log beta1,1) was
      determined to be 8.71+/-0.6 at I = 0. Analysis of the results of ion-exchange
      experiments for the U-Fe-citric acid system indicates the formation of the 1:1:1
      and 1:1:2 ternary species with stability constants (log beta) of 17.10+/-0.41 and
      20.47+/-0.31, respectively, at I= 0.

PMID- 15871252
TI  - Thermodynamic analysis of arsenic methylation.
AB  - The Challenger mechanism for the methylation of arsenic is a repeating sequence
      of a two-electron reduction of pentavalent arsenic As(V) species to trivalent
      arsenic As(III) species followed by a methylation-oxidation reaction forming the
      successive methyl As(V) species. This unusual oxidation-reduction sequence
      prompted an examination of the thermodynamics of these reactions. Quantum
      chemical methods are employed to estimate the thermodynamic parameters for the
      methyl arsenic species. The sequence is thermodynamically favored at neutral pH
      for redox potentials with pe < 0 and methyl cation activities pCH3+ < -3 to -7
      depending on the precise situation analyzed. The observed distribution of methyl
      arsenic species in human urine, which is remarkably constant across many studied
      populations, can be reproduced using an equilibrium model if the formation of TMA
      species is prevented. The estimated thermodynamic parameters are sufficiently
      accurate to evaluate questions of thermodynamic plausibility but not the precise
      details of speciation.

PMID- 15871253
TI  - Spatial variability and uncertainty in ecological risk assessment: a case study
      on the potential risk of cadmium for the little owl in a Dutch river flood plain.
AB  - This paper outlines a procedure that quantifies the impact of different sources
      of spatial variability and uncertainty on ecological risk estimates. The
      procedure is illustrated in a case study that estimates the risks of cadmium for
      a little owl (Athene noctua vidalli) living in a Dutch river flood plain along
      the river Rhine. A geographical information system (GIS) was used to quantify
      spatial variability in contaminant concentrations and habitats. It was combined
      with an exposure and effect model that uses Monte Carlo simulation to quantify
      parameter uncertainty. Spatial model uncertainty was assessed by the application
      of two different spatial interpolation methods (classification and kriging) and
      foraging ranges. The results of the case study show that parameter uncertainty is
      the main type of uncertainty influencing the risk estimate, and to a lesser
      extent spatial variability, while spatial model uncertainty was of minor
      importance. Compared to the deterministically calculated hazard index for the
      little owl (0.9), inclusion of spatial variability resulted in a median hazard
      index that can vary between 0.8 and 1.4. It is concluded that a single estimator
      for a whole flood plain may over- or underestimate risks for specific parts
      within the flood plain. Further research that expands the procedure presented in
      this paper is necessary to improve the incorporation of spatial factors in
      ecological risk assessment.

PMID- 15871254
TI  - Practical considerations on the use of predictive models for regulatory purposes.
AB  - Interest in the use of quantitative structure-activity relationships (QSARs) for
      regulatory purposes has been growing steadily over the years, and many models
      have been evaluated under the guidance and acceptability criteria defined at the
      Setubal workshop held in March 2002. This work explores some of the practical
      issues related to the use of QSARs for regulatory purposes using results obtained
      from rat oral lethality and fish acute toxicity estimates generated from
      computational models (including TOPKAT, MCASE, OASIS, and ECOSAR). Using data
      submitted under the Environmental Protection Agency's (EPA's) High Production
      Volume (HPV) Challenge Program, the results on the quality of the estimations are
      compared using a standard statistical review and an additional classification
      approach in which the hazard predictions were grouped using well-defined
      regulatory criteria (those used in EPA's New Chemical Program). Our results
      indicate that an evaluation of a model's regulatory applicability and predictive
      power is ultimately dependent on the specific criteria used in the assessment
      process. This work also discusses the practical difficulties associated with
      defining the domain of a predictive model using the estimates of four different
      ready biodegradation models and experimental data submitted under the EPA's New
      Chemical program. Our results suggest that the method a model employs for its
      predictions is as important as the training set in determining its domain of
      applicability. Together, these results highlight the challenges associated with
      developing reliable and easily applied acceptability criteria for the regulatory
      use of QSAR models.

PMID- 15871255
TI  - Identification of temperature-dependent water quality changes during a deep well
      injection experiment in a pyritic aquifer.
AB  - Artificial recharge is a technique used increasingly to supplement drinking water
      supplies. To assess the potential water quality changes that occur during
      subsurface passage, a comprehensive deep-well injection experiment was carried
      out for a recharge scheme, where pretreated, aerobic surface water was injected
      at 300 m depth into an anaerobic aquifer. Water quality parameters were recorded
      over the 854-days long injection phase. The evolution of the major ion and redox
      chemistry was analyzed with a three-dimensional reactive multicomponent transport
      model. It was found that the oxidation of pyrite was the main driverforwater
      quality changes and that reaction rates depended significantly on the
      spatially/temporally varying groundwater temperature. With the temperature
      dependency of the oxidation reactions incorporated into the model, the
      simulations give an accurate picture of the temporal and spatial evolution of the
      hydrochemical changes that occurred during the experiment. To delineate the
      influence of physical and chemical processes on local concentration changes the
      results of the reactive transport model simulations were compared with the
      corresponding results from nonreactive simulations. The study emphasizes the
      suitability of mechanistic multicomponent reactive transport modeling as an
      integrative tool for data analysis when physical transport and chemical processes
      interact.

PMID- 15871256
TI  - Application of quantitative fluorescence and absorption-edge computed
      microtomography to image metal compartmentalization in Alyssum murale.
AB  - This paper shows that synchrotron-based fluorescence and absorption-edge computed
      microtomographies (CMT) are well-suited for determining the compartmentalization
      and concentration of metals in hyperaccumulating plant tissues. Fluorescence CMT
      of intact leaf, stem, and root samples revealed that Ni concentrated in stem and
      leaf dermal tissues and, together with Mn, in distinct regions associated with
      the Ca-rich trichomes on the leaf surface of the nickel hyperaccumulator Alyssum
      murale "Kotodesh". Metal enrichment was also observed within the vascular system
      of the finer roots, stem, and leaves but absent from the coarser root, which had
      a well-correlated metal coating. Absorption-edge CMT showed the three-dimensional
      distribution of the highest metal concentrations and verified that epidermal
      localization and Ni and Mn co-localization at the trichome base are phenomena
      that occurred throughout the entire leaf and may contribute significantly to
      metal detoxification and storage. Ni was also observed in the leaf tips, possibly
      resulting from release of excess Ni with guttation fluids. These results are
      consistent with a transport model where Ni is removed from the soil by the finer
      roots, carried to the leaves through the stem xylem, and distributed throughout
      the leaf by the veins to the dermal tissues, trichome bases, and in some cases
      the leaf tips.

PMID- 15871257
TI  - Adaptation of dry nephelometer measurements to ambient conditions at the
      Jungfraujoch.
AB  - In a numerical study the influence of relative humidity (RH) on aerosol
      scattering coefficients sigma was investigated. Based on a core/coating aerosol
      model, RH enhancement factors for scattering, xi(RH) = sigma(RH)/sigma(RH = 0),
      were calculated for the wavelengths lambda = 450, 550, and 700 nm for a summer
      and a winter case. The investigation was adapted to the situation (e.g., chemical
      composition, particle size distributions, hygroscopic behavior) of the high
      alpine site Jungfraujoch (JFJ, 3580 m asl), where long-term measurements of dry
      aerosol scattering coefficients are performed at these wavelengths. The presented
      results are therefore representative of the lower free troposphere above a
      continent. The RH enhancement factors at a specific RH strongly depend on the
      average particle size. For example, at RH = 85% they vary between approximately
      1.2 and approximately 2.7 in summer and between approximately 1.4 and
      approximately 3.8 in winter. It is shown that there is a strong relationship
      between xi and the Angstrom exponent a (based on scattering only) of the dry
      aerosol, which is directly derived from the dry scattering measurements. This
      allows for parametrizing xi for a specific wavelength and season with a and RH.
      The parametrization is applicable for RH up to approximately 90%--for higher RH
      the underlying hygroscopic models become unreliable--and for a between
      approximately -0.25 and approximately 2.75, which covers the range observed at
      the JFJ. Also addressed is a systematic error in the dry scattering coefficients
      measured with a nephelometer previously discussed in the literature, which arises
      from nonidealities in the angular intensity distribution of the light inside the
      instrument. This effect also depends strongly on the particle size and can be
      described by a correction factor C that can be parametrized with a. The
      scattering coefficient corrected for measurement artifacts at ambient RH for
      specific wavelength and season therefore can be estimated from the uncorrected
      dry nephelometer scattering coefficient sigma(neph) as sigma(a, RH) = C(a) x
      xi(a, RH) x sigma(neph). As additional information only ambient RH data are
      needed. The 95% confidence bound of this total correction ranges from less than
      5% for low RH and large a up to approximately 40% for high RH and small a.

PMID- 15871258
TI  - Comparison of mass-based and non-mass-based particle measurement systems for
      ultra-low emissions from automotive sources.
AB  - Drastic reduction in particle emissions of diesel-powered vehicles and new
      findings on the health impact of particles raise the question of a more sensitive
      measurement procedure. In this paper, 16 different particle mass measurement
      systems are compared on a diesel heavy-duty engine equipped with a particle
      filter to investigate their feasibility for particle characterization for future
      ultra-low concentration levels. The group of instruments comprises mass-related
      methods (filter methods, laser-induced incandescence, photoacoustic detection,
      photoelectric charging, combined inertial and mobility sizing, opacity) as well
      as non-mass-related methods (CPC, diffusion battery, diffusion charger, ELPI,
      light scattering). The instruments are compared on the basis of repeatability,
      limit of detection, sensitivity, time resolution and correlation with the
      regulated gravimetric filter method, and elemental carbon fraction (EC). Several
      time-resolved methods show good performance and give reliable results.
      Opacimeters and light scattering, however, reveal shortcomings at these low
      concentrations. For all time-resolved advanced methods, poor correlation with the
      regulated filter method is observed, but most of them show good correlation with
      the EC fraction of the particles. This outcome demonstrates the crucial role of
      the sampling conditions for measurement methods that do not exclude volatile
      material from detection. A clear improvement in sensitivity is observed when non
      mass-based instruments are applied (e.g., number or surface-related methods). The
      results reveal that reliable measurement methods exist for future measurement
      procedures. However, a change in the measurement method will lead to a
      discontinuity in the inventories, making it difficult to compare the particle
      emissions from future and past vehicle generations.

PMID- 15871259
TI  - Nonderivatization analytical method of fatty acids and cis pinonic acid and its
      application in ambient PM2.5 aerosols in the greater Vancouver area in Canada.
AB  - A nonderivatization analytical method has been developed to analyze C6-C20 fatty
      acids and cis-pinonic acid on a GC/ FID and a GC/MSD using a polar DB-FFAP
      capillary column. On the GC/FID, the response was highly linear over
      concentration ranges >2 orders of magnitude (R2 = 1.00). Using a mixed solvent of
      dichloromethane (DCM): methanol (3:1, v/v) and an extraction temperature of 40
      degrees C, the method recoveries of the acids from spiked filters were 81-115%
      based on deuterated surrogates, and the relative standard deviations were <12%.
      The recoveries were mainly controlled by the extraction temperature. At 40
      degrees C the acids in sample extracts were stable for at least 12 months, while
      at 80 degrees C, unintended esterization of the acids by methanol was found that
      reduces their stability in the sample extracts. The analysis of the acids in
      PM2.5 samples from NIST using this nonderivatization method showed that the
      efficiency and accuracy were comparable to the derivatization method. Compared
      with existing derivatization methods, the method is accurate and sensitive, yet
      simple to use. This method was applied to PM2.5 ambient aerosols collected from a
      forest site and at a traffic tunnel outlet in the greater Vancouver area in
      Canada. Total fatty acids (sum of C6-C20) in the aerosols were measured as 20.2
      138.7 ng/m3 at the forest site and 100.2-264.6 ng/m3 at the tunnel site. The cis
      pinonic acid concentrations were 1.6-44.2 ng/m3 in the forest and from below
      detection to 6.5 ng/m3 at the tunnel outlet.

PMID- 15871260
TI  - Novel algorithm for tomographic reconstruction of atmospheric chemicals with
      sparse sampling.
AB  - Numerical studies were performed to evaluate a new air monitoring method for
      reconstructing chemical exposures and source emissions, based upon optical remote
      sensing (ORS) and computed tomography (CT). With an ORS-CT system, two
      dimensional maps of chemical concentrations can be created that have good spatial
      and temporal resolution. The mathematical algorithm used to compute the
      distribution is critical for accurate and useable reconstructions of the
      concentrations. In this research, a novel reconstruction method was tested that
      uses maximum likelihood expectation maximization (MLEM) combined with two
      techniques called grid-translation and multi-grid (GT-MG). To evaluate this
      method, computer simulations were performed using 120 test maps of varying
      complexity and a simulated ORS system with four instruments and a total of 40
      path-integrated measurements. The results were quantitatively compared with two
      previously used reconstruction methods (single-grid and grid-translation).
      Results using the GT-MG method were dramatically improved over previously used
      methods. Quantitatively, peak exposure errors were reduced by up to 85% and
      artifacts were dramatically minimized.

PMID- 15871261
TI  - Differential pressure as a measure of particulate matter emissions from diesel
      engines.
AB  - A diesel particulate matter analyzer capable of direct, real-time measurement of
      engine exhaust particulate is necessary to effectively institute source control
      technology currently being used on diesel equipment and to ensure that the
      control measures are working. To investigate the potential of a differential
      pressure monitor to measure diesel particulate matter in undiluted exhaust,
      samples were collected from three different diesel engines--Kubota, Isuzu, and
      Deutz--running under 12 different RPM and load scenarios. These measurements were
      compared to elemental carbon concentrations in the sampled exhaust as determined
      by using the NIOSH 5040 analytical method. Elemental carbon is used as a
      surrogate measurement for diesel particulate matter. The results of the two data
      sets were then compared using a linear regression analysis. The coefficient of
      determination (or R2) was calculated to be 0.98, 0.94, and 0.74 for the Kubota,
      Deutz, and Isuzu engines, respectively. R2 values of this magnitude indicate that
      this method can be successful in estimating elemental carbon emissions in the
      engines tested. In addition, for replicate samples, the coefficient of variation
      ranged from 7.1% to 10.2% with an average of 8.5%. These data indicate that this
      method could prove useful to mechanics as they work to maintain engines and DPM
      control technologies.

PMID- 15871262
TI  - Convenient new chemical actinometer based on aqueous acetone, 2-propanol, and
      carbon tetrachloride.
AB  - A convenient new chemical actinometer was developed to measure the spectral
      output of laboratory ultraviolet (UV) light sources over the wavelength range of
      260-330 nm. It can also be used to measure solar UV irradiance (< or =325 nm).
      The actinometer is based on the photoreduction of aqueous carbon tetrachloride
      (CT) to chloroform (CF) in the presence of acetone (the chromophore) and 2
      propanol (the reductant). In all cases, CT disappearance (and CF formation)
      followed zero-order kinetics over 95% of the reaction. The slope of the linear
      decay curve forms the basis of the new actinometer, which was calibrated using
      ferrioxalate actinometry. Quantum yields were measured at 10 nm intervals and
      were found to be uniform throughout the range of 260-300 nm. As expected, quantum
      yields gradually decreased to zero asthe wavelength was increased from 300 to 340
      nm. The high quantum yields (approximately 150), low sensitivityto room light,
      and the straightforward determination of [CT] and [CF] by gas chromatography
      offer significant advantages over some other chemical actinometers, which might
      require the preparation and purification of light-sensitive compounds in a
      darkened environment and long exposure times.

PMID- 15871263
TI  - Optimizing contaminant desorption and bioavailability in dense slurry systems. 1.
      Rheology, mechanical mixing, and PAH desorption.
AB  - Intermittently mixed batch reactor (IMBR) systems were employed to evaluate the
      effects of mechanical mixing and corresponding power consumption on rates of
      phenanthrene desorption from natural and synthetic model sorbent phases to the
      aqueous phase in dense slurry reactors. Sorbent slurries comprising 57-67% (w/w)
      solids exhibited non-Newtonian (pseudoplastic) fluid behaviors, with apparent
      viscosities varying with shear rate. Dimensionless power numbers varied inversely
      with the Reynolds number under laminar flow conditions, indicating that small
      increases in mixing revolution number and auger size effect significant increases
      in power and torque requirements for the mechanical mixing of dense slurries.
      Rates of release of phenanthrene associated with rapidly desorbing or labile
      fractions of sorbent organic matter (SOM) to the aqueous phase were markedly
      enhanced by relatively low-level auger mixing, but significantly less further
      enhancement was observed as higher levels of mixing were applied. Conversely,
      desorption of phenanthrene associated with slowly desorbing or resistant
      fractions of SOM was relatively unaffected by auger mixing, being limited as it
      is by slow intraparticle-scale diffusion processes that are not enhanced by
      reactor-scale mixing. The experimental results lead to and support a conclusion
      that auger mixing at relatively low intensity is an attractive strategy for
      optimizing dense slurry reactor systems for remediation of hydrophobic organic
      contaminants associated with labile (rapidly desorbing) fractions of SOM with
      respect to performance efficiency and cost-effectiveness.

PMID- 15871264
TI  - Optimizing contaminant desorption and bioavailability in dense slurry systems. 2.
      PAH bioavailability and rates of degradation.
AB  - The effects of mechanical mixing on rates of polycyclic aromatic hydrocarbon
      (PAH) biodegradation in dense geosorbent slurry (67% solids content, w/w) systems
      were evaluated using laboratory-scale intermittently mixed batch bioreactors. A
      PAH-contaminated soil and a phenanthrene-sorbed mineral sorbent (alpha-Al2O3)
      were respectively employed as slurry solids in aerobic and anaerobic
      biodegradation studies. Both slurries exhibited a characteristic behavior of
      pseudoplastic non-Newtonian fluids, and the impeller revolution rate and its
      diameter had dramatic impacts on power and torque requirements in their laminar
      flow mixing. Rates of phenanthrene biodegradation were markedly enhanced by
      relatively low-level auger mixing under both aerobic and anaerobic (denitrifying)
      conditions. Parameters for empirical models correlating biodegradation rate
      coefficient (k(b)) values to the degree of mixing were similar to those for
      correlations between mass transfer (desorption) rate coefficient (k(r)) values
      for rapidly desorbing fractions of soil organic matter and degree of mixing
      reported in a companion study, supporting a conclusion that performance-efficient
      and cost-effective enhancements of PAH mass transfer (desorption) and its
      biodegradation processes can be achieved by the introduction of optimal levels of
      reactor-scale mechanical mixing.

PMID- 15871265
TI  - Reductive debromination of polybrominated diphenyl ethers by zerovalent iron.
AB  - Polybrominated diphenyl ethers (PBDEs) are a new class of global, persistent, and
      toxic contaminants, which need proper remediation technologies. PBDE degradation
      in the environment is not well understood. In this study, degradation of PBDEs
      with zerovalent iron was investigated with six BDEs, substituted with one to 10
      bromines. Within 40 days 92% of BDE congener 209 was transformed into lower bromo
      congeners. During the initial reaction period of BDE 209 (<5 days), hexa- to
      heptabromo BDEs were the most abundant products, but tetra- to pentabromo
      congeners were dominant after 2 weeks. The amount of mono- to tribromo BDEs was
      steadily increased during the experiments. BDEs 28, 47, 66, and 100 also showed a
      stepwise accumulation of lower bromo congeners. No oxidation products were
      detected in all experiments. The results showed that a stepwise debromination
      from n-bromoto (n-1)-bromodiphenyl ethers was the dominant reaction in all
      congeners. The reaction rate constants of lower bromo BDEs decreased as the
      number of bromines decreased. The initial reductive debromination rate constants
      were positively correlated with the heats of formation of BDEs. The preferential
      accumulation of specific congeners was observed in the experiment with BDEs 28,
      47, 66, and 100, where the most abundant products were BDEs 15, 28, 37, and 47,
      respectively. Reactions proceeded to form more stable and less brominated
      products that have lower heats of formation. Almost all the possible isomers from
      a specific parent BDE were found in all the experiments, which was probably due
      to the small difference of heat of formation between the products (2-5 kcal/mol).
      Reactions of all congeners proceeded fast at the initial phase (<5 days) followed
      by a slow reaction. The rate of reductive debromination of BDE 209 was slower
      with environmentally relevant sulfide minerals (iron sulfide and sodium sulfide).
      However, the product congener pattern, produced by sulfide mineral catalysis, was
      nearly similar with that of zerovalent iron treatment. This may be a possible
      source of lower brominated BDEs in the environment. Debromination of PBDEs by
      zerovalent iron has high potential values for remediation of PBDEs in the
      environment.

PMID- 15871267
TI  - Accelerated transformation and deactivation of erythromycin in superheated water.
      1. Temperature effects, transformation rates, and the impacts of dissolved
      organic matter.
AB  - The presence of antibiotics and other pharmaceuticals in the environment is of
      increasing concern. The stringent treatment of point discharges of antibiotic
      wastes holds promise as an approach for curtailing growing trends of microbial
      resistance. The work described in this two-part series explores the use of
      superheated water as a medium forthe accelerated transformation and deactivation
      of a specific target antibiotic, erythromycin. Part 1 of the series focuses on
      parent compound conversion, and Part 2 examines transformation mechanisms and
      reaction products. This paper, Part 1, highlights the results of reactor studies
      performed in both batch and flow-through modes. The data presented confirm that
      accelerated conversion of erythromycin, based on parent compound disappearance as
      measured by high-pressure liquid chromatography, occurs in water under
      superheated conditions. Given an initial erythromycin concentration of 50 mg/L,
      greaterthan 85% apparent conversion was achieved within 30 min in the batch
      system at all temperatures investigated in the range from 125 to 200 degrees C.
      The presence of dissolved organic matter extracted from two natural soil
      materials, at concentrations of 2.5-20 mg/L, was shown to have little effect on
      the overall extent of transformation of erythromycin in the batch system. The
      rates of decomposition observed were found to be best described by a psuedo-first
      order expression, one in which the rate coefficient increased linearly with
      increasing initial concentration of the antibiotic. First-order rate behavior was
      verified in subsequent flow reactor experiments. The temperature dependence of
      rate was also examined, and an activation energy of 68.8 kJ/mol was determined.

PMID- 15871266
TI  - Fate of wastewater effluent hER-agonists and hER-antagonists during soil aquifer
      treatment.
AB  - Estrogen activity was measured in wastewater effluent before and after polishing
      via soil-aquifer treatment (SAT) using both a (hER-beta) competitive binding
      assay and a transcriptional activation (yeast estrogen screen, YES) assay. From
      the competitive binding assay, the equivalent 17alpha-ethinylestradiol (EE2)
      concentration in secondary effluent was 4.7 nM but decreased to 0.22 nM following
      SAT. The YES assay indicated that the equivalent EE2 concentration in the same
      effluent sample was below the method-detection limit (<2.5 x 10(-3) nM) but
      increased to 0.68 nM in effluent polished via SAT processes. It was hypothesized
      thattest-dependent differences arose because the competitive binding assay
      responds positively to both estrogen mimics and anti-estrogens; the YES assay
      responds to estrogen mimics, but test response is inhibited by anti-estrogens.
      The hypothesis was supported when organics extracted from wastewater effluent
      inhibited the YES test response to EE2 (anti-estrogenic effect). A similar
      extract prepared from SAT-polished effluent augmented the EE2 curve (agonist
      response). When hydrophobic organics in secondary effluent were fractionated,
      assay results indicated that several physically distinct anti-estrogens were
      present in the sample. From this work, it is evident that transcription
      activation bioassays alone should not be relied upon to measure estrogenic
      activity in complex environmental samples because the simultaneous presence of
      both agonists and antagonist compounds can yield false negatives. Multiple in
      vitro bioassays, sample fractionation or tests designed to measure anti
      estrogenic activity can be used to overcome this problem. It is also clear that
      there are circumstances under which SAT does not completely remove estrogenic
      activity during municipal wastewater effluent polishing.

PMID- 15871268
TI  - Accelerated transformation and deactivation of erythromycin in superheated water.
      2. Transformation reactions and bioassays.
AB  - The work presented in this second part of a two-part series on the accelerated
      transformation of erythromycin in superheated water focuses on the chemical
      nature and resultant antimicrobial implications of the overall reaction observed.
      Analyses of reactor effluents employing infrared spectroscopy and liquid
      chromatography/mass spectrometry indicated that the initial step in the
      decomposition pathway is one of dehydration. Subsequent hydrolysis in the
      presence of an acetate buffer appeared to result in the loss of the sugar
      cladinose. Chemical transformation under superheated conditions was tied to the
      loss of antibiotic function by an agar dilution test. The sensitivity of this
      test was verified by determination of the minimum inhibitory concentration (MIC)
      of erythromycin corresponding to each of two test microorganisms. MIC values for
      the selected strains of Escherichia coli and Bacillus subtilis were 35 and 0.5
      mg/L, respectively. To relate the loss of antimicrobial activity to increased
      reaction temperature and thus to increased extent of parent compound
      transformation to microbially benign intermediates, bioassays using E. coli as
      test microorganism were performed on flow reactor effluents resulting from
      reaction of initial erythromycin concentrations of 75-150 mg/L.

PMID- 15871269
TI  - Breakage, regrowth, and fractal nature of natural organic matter flocs.
AB  - The growth, breakage, regrowth, and fractal nature of flocs was investigated by
      use of a laser diffraction particle sizing device. A range of coagulants were
      investigated for the coagulation of natural organic matter (NOM) and compared to
      other coagulated systems. The results showed NOM floc structural characteristics
      varied in steady-state size depending upon which coagulant was used. When
      compared to other systems, the order of floc size was Fe precipitate > Fe-NOM >
      latex (in NaCl solution). Floc regrowth after exposure to high shear was limited
      for all of the flocs under investigation other than for latex in an inert
      electrolyte. This highlighted differences in the internal bonding structure of
      flocs, with the results suggesting that physical bonds have a capacity to re-form
      after breakage. Fractal dimension analysis by small-angle laser light scattering
      (SALLS) had limited applicability to large flocs that dominated all of the
      systems under investigation, but the degree of compaction increased as flocs were
      broken in high shear. This provided a possible mechanistic reason for the
      irreversible breakage seen.

PMID- 15871270
TI  - Efficient recovery of CO2 from flue gas by clathrate hydrate formation in porous
      silica gels.
AB  - Thermodynamic measurements and NMR spectroscopic analysis were used to show that
      it is possible to recover CO2 from flue gas by forming a mixed hydrate that
      removes CO2 preferentially from CO2/N2 gas mixtures using water dispersed in the
      pores of silica gel. Kinetic studies with 1H NMR microimaging showed that the
      dispersed water in the silica gel pore system reacts readily with the gas, thus
      obviating the need for a stirred reactor and excess water. Hydrate phase
      equilibria for the ternary CO2-N2-water system in silica gel pores were measured,
      which show that the three-phase hydrate-water-rich liquid-vapor equilibrium
      curves were shifted to higher pressures at a specific temperature when the
      concentration of CO2 in the vapor phase decreased. 13C cross-polarization NMR
      spectral analysis and direct measurement of the CO2 content in the hydrate phase
      suggested that the mixed hydrate is structure I at gas compositions of more than
      10 mol % CO2, and that the CO2 molecules occupy mainly the more abundant
      5(12)6(2) cages. This makes it possible to achieve concentrations of more than 96
      mol % CO2 gas in the product after three cycles of hydrate formation and
      dissociation. 1H NMR microimaging showed that hydrate yields of better than 85%,
      based on the amount of water, could be obtained in 1 h when a steady state was
      reached, although approximately 90% of this yield was achieved after
      approximately 20 min of reaction time.

PMID- 15871271
TI  - Formation of refractory ring-expanded triazine intermediates during the
      photocatalyzed mineralization of the endocrine disruptor amitrole and related
      triazole derivatives at UV-irradiated TiO2/H2O interfaces.
AB  - Amitrole (ATz, 3-amino-1H-1,2,4-triazole) is a widely employed herbicide with
      strong estrogenic activity that can lead to abnormalities of the thyroid gland
      and can cause mutations. The photocatalytic transformation of ATz was carried out
      at the UV-irradiated TiO2/H2O interface, along with the triazole derivatives Tz
      (1H-1,2,4-triazole) and DaTz (3,5-diamino-1H-1,2,4-triazole) to assess the
      decomposition of these herbicides, to identify intermediates, and to elucidate
      some mechanistic details of the ATz degradation. Conversion of the nitrogens of
      these triazoles to NH4+ and/ or NO3- ions occurs competitively and depends on the
      number of amine functions on the five-membered triazole rings.
      Photomineralization of the substrates in terms of loss of nitrogen to NH4+/NO3-
      was rather low (ca. 25-40%) for each of the triazoles, whereas evolution of CO2
      (loss of TOC) was more significant (60-70%), indicating considerable retention of
      nitrogen in the intermediate products. UV-Vis spectroscopy, TOC assays, FT-IR
      spectroscopy, proton NMR spectrometry, electrospray LC-MS, and molecular orbital
      calculations were brought to bear in assessing the temporal course of the
      photocatalyzed process(es). Results show that after cleavage of the triazole
      ring, the various intermediate fragments recombine to yield ring-expanded six
      membered triazine intermediates, which slowly degrade to give the refractory
      cyanuric acid under the conditions used.

PMID- 15871272
TI  - Multi objective optimization of the setup of a surfactant-enhanced DNAPL
      remediation.
AB  - Surfactant-enhanced aquifer remediation (SEAR) is widely considered a promising
      technique to remediate dense nonaqueous phase liquid (DNAPL) contaminations in
      situ. The costs of a SEAR remediation are important and depend mostly on the
      setup of the remediation. Costs can be associated with the installation of
      injection and extraction wells, the required time of the remediation (and thus
      labor costs, lease of installations, and energy), the extracted water volume (the
      purification of the extracted water), and the injected surfactant amount. A cost
      effective design of the remediation setup allows an optimal use of resources. In
      this work, a SEAR remediation was simulated for a hypothetical typical DNAPL
      contamination. A constrained multi-objective optimization of the model was
      applied to obtain a Pareto set of optimal remediation strategies with different
      weights for the two objectives of the remediation: (i) the maximal removal of
      DNAPL mass (ii) with a minimal total cost. A relatively sharp Pareto front was
      found, showing a considerable tradeoff between DNAPL removal and total
      remediation costs. These Pareto curves can help decision makers select an optimal
      remediation strategy in terms of cost and remediation efficiency depending on
      external constraints such as the available budget and obligatory remediation
      goals.

PMID- 15871273
TI  - Size exclusion chromatography to characterize DOC removal in drinking water
      treatment.
AB  - A full-scale (110 ML/d) potable water treatment plant (WTP) based on the MIEX
      process, an innovative new process based on a strong base anion-exchange resin
      with magnetic properties, has been operating in Perth Western Australia since
      2001. This plant has been configured so that a combined MIEX-coagulation (MIEX-C)
      process can be operated in parallel with a conventional enhanced coagulation (EC)
      process, allowing comparison of the performance of the two processes. Here, we
      report the use of size exclusion chromatography (SEC) to compare the removal of
      different apparent molecular weight (AMW) fractions of DOC by the two processes.
      Water was sampled from five key locations within the WTP, and SEC was carried out
      using three different on-line detector systems, DOC-specific detection, UV
      absorbance detection at lambda = 254 nm, and fluorescence detection (lambda(ex) =
      282 nm; lambda(em) = 353 nm). This approach provided information on the chemical
      nature of the DOC comprising the various AMW fractions. The study showed that the
      MIEX-C process outperformed the EC process with greater removal of DOC in each of
      the eight separate AMW fractions identified. While EC preferentially removed the
      fractions of highest AMW, and those exhibiting the greatest aromatic (humic)
      character, MIEX-C removed DOC across all AMW fractions and did not appear to
      discriminate as strongly on the basis of differences in aromatic character or
      AMW. The results demonstrate the benefits of combining these complementary
      treatment processes. The study also demonstrates the utility of SEC coupled with
      multiple detection systems in determining the characteristics of various AMW
      components of DOC.

PMID- 15871275
TI  - Activated carbon load equalization of discontinuously generated acetone and
      toluene mixtures treated by biofiltration.
AB  - Studies were conducted to evaluate use of granular activated carbon (GAC) as a
      passively operated load-equalization mechanism for biofilters treating gas
      streams with dynamically varying (intermittent) pollutant loading. In the initial
      stage of research, abiotic fixed-bed sorption experiments and numerical modeling
      were conducted to assess the degree of load-equalization achieved by GAC columns
      for air flows containing intermittent loading of acetone and toluene present as
      single-component contaminants and as a mixture. In the subsequent stage of
      research, an integrated system consisting of a GAC column in series before a
      biofilter was used to treat a gas stream containing a mixture of acetone and
      toluene at influent concentrations of 430 ppm(v) and 100 ppm(v) respectively. To
      simulate loading conditions expected from an industrial process with intermittent
      operation, contaminated air was supplied 8 h/day and uncontaminated air was
      supplied 16 h/day. The system was operated with different empty bed contact
      times, as low as 2.5 s for the GAC column and 14.5 s for the biofilter.
      Performance of an additional, conventionally operated biofilter (i.e., without
      GAC load equalization system) was used as a basis of comparison. Data are
      presented which clearly demonstrate that passively operated GAC load-dampening
      systems installed in series before biofilters can lead to more uniform loading as
      a function of time and thereby improve biofilter treatment performance. Results
      also demonstrate that, because of competitive sorption, the degree of load
      equalization achieved for different constituents in multi-contaminant gas streams
      can vary markedly. A pore and surface diffusion model (PSDM) was able to
      accurately predict the degree of load-dampening achieved by GAC columns for
      single and multicomponent waste gases.

PMID- 15871276
TI  - Effective recovery of harmful metal ions from squid wastes using subcritical and
      supercritical water treatments.
AB  - The Japanese common squid wastes contained high concentration of metal ions such
      as 31.7 ppm Cd(II), 264.0 ppm Cu(II), and 140.0 ppm Zn(II). The use of sub- and
      supercritical water treatment has been investigated as a new method of recovering
      heavy metals from squid wastes. The reactions were carried out in the temperature
      range of 443-653 K, a pressure range of 0.792-30 MPa, and reaction times of 1-40
      min. The wastes were decomposed into soluble proteins, organic acids, amino
      acids, and so on in the aqueous phase, and the fat and oil were extracted by sub-
      and supercritical water. The maximum yields on concentration of Cd(II), Cu(II),
      and Zn(II) in the solid, fat, and oil phases were found at 653, 573, and 513-573
      K, respectively. The aqueous phase showed the lowest concentration of the metal
      ions (0.05-0.5 ppm). The distribution coefficient of metal ions in the fat,
      solid, and oil phases to aqueous phase were examined and found highest in the fat
      phase (max. 48 000). The solid phase (max. 39,000) and oil phase (max. 245)
      showed the second and third highest. Moreover, the fat and oil phases produced
      during this method act as chelating agents to catch metal ions with an order of
      recovery of Cu2+ > Zn2+ > Cd2+ and Zn2+ > Cu2+ > Cd2+, respectively.

PMID- 15871274
TI  - Water purification from organic pollutants by optimized micelle-clay systems.
AB  - Removal of anionic pollutants (imazaquin, sulfentrazone, sulfosulfuron) and
      neutral pollutants (alachlor, acetochlor, chlorotoluron, bromacil) from water by
      micelles preadsorbed on montmorillonite was studied. Micelles of
      octadecyltrimethylammonium and benzyldimethylhexadecylammonium (BDMHDA) were
      used. The micelle-clay systems (1% w/w) removed 87-99% of the pollutants from
      their water solutions containing 1-33 mg/L of herbicide. The nature of the
      headgroup of the organic cation, which forms the micelles, is critical.
      Desorption of imazaquin and acetochlor from 0.3% (w/w) suspension of BDMHDA-clay
      complex after 24 h was around 7% in the range of adsorbed amounts from 0.6 to
      15.3 mg/g. These results indicate rather slow rates and small extents of release
      of pollutants from micelle-clay complexes. Column filters (25 cm) made of a
      mixture of quartz sand and BDMHDA micelle-clay complex at 100:1 w/w ratio removed
      at least 99% of above pollutants from initial solutions containing 10 mg/L; 99.5
      and 97% of sulfosulfuron and alachlor were removed from their initial solutions
      containing 200 and 5 microg/L, respectively. These data indicate that micelle
      clay complexes are very efficient for water purification from organic
      contaminants.

PMID- 15871277
TI  - Low-temperature complete combustion of a dilute mixture of methane and propane
      over transition-metal-doped ZrO2 catalysts: effect of the presence of propane on
      methane combustion.
AB  - Complete combustion of dilute methane alone or a dilute mixture of methane and
      propane over transition-metal (viz. Mn, Co, Cr, Fe, and Ni)-doped ZrO2 (cubic)
      catalysts at different temperatures (523-873 K) and a space velocity of 51,000
      cm3 x g(-1) x h(-1) has been investigated for controlling methane and propane
      emissions from exhaust gases. The catalysts are compared for their catalytic
      ignition temperature and activity in the combustion of propane and methane in the
      presence of each other. The methane combustion activity of all the catalysts is
      strongly influenced by the presence of propane; it is decreased markedly. In the
      combustion of mixed methane and propane the Mn-doped ZrO2 and Cr-doped ZrO2
      catalysts show the highest activity in the combustion of methane and propane,
      respectively; the Ni-doped ZrO2 shows the lowest activity in both cases. In the
      combustion of mixed methane and propanethe propane combustion is enhanced butthe
      methane combustion retarded when the Cr-doped ZrO2 and Mn-doped ZrO2 catalysts in
      a 1:1 ratio are used together in different ways (mixed or in layers).

PMID- 15871278
TI  - Removal of copper from contaminated soil by use of poly(amidoamine) dendrimers.
AB  - This study characterizes poly(amidoamine) (PAMAM) dendrimers of various
      generations and terminal functional groups for removal of copper(II) in a sandy
      soil. Effects of dendrimer dose, generation number, pH, terminal functional
      groups, and ionic strength on the removal efficiency were investigated through a
      series of column tests. Over 90% of copper initially sorbed in the soil was
      removed by use of approximately 66 bed volumes of 0.10% (w/w) of a generation 4.5
      dendrimer with carboxylate terminal groups at pH 6.0. On the basis of equal
      equivalent dose, dendrimers of lower generation removed more copper. Lowering pH
      enhanced copper removal for all dendrimers tested. In contrast, types of terminal
      groups (carboxylate, amine, or hydroxyl) showed a modest effect on the removal
      efficiency. Results from a sequential extraction procedure suggested that
      dendrimers removed primarily exchangeable and carbonate-bound copper. The
      residual copper in treated soil is predominantly bound with soil organic matter
      (SOM), which is much less available physical-chemically or biologically. Spent
      dendrimers were recovered through nanofiltration with a commercially available
      nanofilter. Upon acid regeneration, recovered dendrimers were reused and
      performed as well as the virgin dendrimers. The dendrimers may be used as
      reusable, high-capacity extracting agents for in situ removal of heavy metals
      from contaminated soils.

PMID- 15871279
TI  - Simultaneous and synergistic conversion of dyes and heavy metal ions in aqueous
      TiO2 suspensions under visible-light illumination.
AB  - This study reports synergistic effects in the simultaneous conversion of dyes and
      heavy metal ions in aqueous TiO2/dye/metal ion systems (ternary components) under
      visible light (lambda > 420 nm). TiO2/Cr(VI)/Acid Orange 7 (AO7),
      TiO2/Cr(VI)/Rhodamine B (RhB), TiO2/Ag+/AO7, and TiO2/Ag+/RhB were chosen as test
      systems. Although dyes can be degraded in TiO2 suspensions under visible light,
      their removal rates were markedly enhanced in the presence of metal ions.
      Similarly, the reduction rates of metal ions in visible-light-illuminated TiO2
      suspensions were negligible, but they were highly accelerated with dyes present.
      In particular, the synergistic effect in the ternary system of TiO2/Cr(VI)/AO7
      was outstanding. The presence of dissolved oxygen increased the photoreduction
      rate of Cr(VI) despite the fact that Cr(VI) and O2 are competing electron
      acceptors. This is ascribed to in-situ photogenerated H2O2 from O2, which acts as
      a reductant of Cr(VI). RhB and Ag+ ions could be also converted simultaneously
      under visible light both in the presence and absence of TiO2. The visible-light
      induced reduction of Ag+ did not occur at all in TiO2/Ag+ system, but it was
      enabled in both TiO2/Ag+/ RhB and TiO2/Ag+/AO7 to generate Ag particles. On the
      other hand, the binary systems of Cr(VI)/AO7, Ag+/AO7, and Ag+/RhB show
      significant visible-light activities for the conversion of both dye and metal
      ion. In this case, metal ions and dyes seem to form complexes that induce
      intracomplex electron transfers upon visible-light absorption. The Cr(VI)/RhB
      system, however, exhibited insignificant visible-light reactivity.

PMID- 15871281
TI  - Description of transport mechanism during the elimination of copper(II) from
      wastewaters using supported liquid membranes and Acorga M5640 as carrier.
AB  - The kinetics of copper facilitated transport through a flat-sheet supported
      liquid membrane is investigated, using the commercially available oxime Acorga
      M5640 as ionophore, as a function of hydrodynamic conditions, stripping phase
      composition, concentration of copper(II), and pH of the source phase and carrier
      concentration in the membrane phase. The performance of the system is also
      compared using organic diluents of different nature (aliphatic or aromatic) and
      against other available oxime extractants (LIX 860, LIX 622, LIX 973N and LIX 84
      I). A model is presented that describes the transport mechanism, consisting of
      diffusion through source side aqueous diffusion layer, a fast interfacial
      chemical reaction, and diffusion carrier and its metal complex through the
      organic membrane. The organic membrane diffusional resistance (delta(org)) and
      aqueous diffusional resistances (delta(aq)) were calculated from the proposed
      model, and their values were 9.3 x 10(-7) and 46565 s/cm, respectively. It was
      observed that the copper flux across the membrane tends to reach a plateau at
      high concentration of copper or low concentration of H+ owing to carrier
      saturation within the membrane and leads to a diffusion-controlled process. The
      values of the apparent diffusion coefficient (Dorg(a)) and limiting metal flux
      (Jlim) were calculated from the limiting conditions and found to be 5.2 x 10(-11)
      and 1.9 x 10(-9) mmol/cm2 s, respectively. The values of the bulk diffusion
      coefficient (Db,org) and diffusion coefficient (Dorg) calculated from the model
      were 4.8 x 10(-10) and 1.3 x 10(-10) cm2/s,respectively. The method had proven
      its feasibility to recover copper(II) from wastewaters.

PMID- 15871282
TI  - Systematic procedure for designing processes with multiple environmental
      objectives.
AB  - Evaluation of multiple objectives is very important in designing environmentally
      benign processes. It requires a systematic procedure for solving multiobjective
      decision-making problems due to the complex nature of the problems, the need for
      complex assessments, and the complicated analysis of multidimensional results. In
      this paper, a novel systematic procedure is presented for designing processes
      with multiple environmental objectives. This procedure has four steps:
      initialization, screening, evaluation, and visualization. The first two steps are
      used for systematic problem formulation based on mass and energy estimation and
      order of magnitude analysis. In the third step, an efficient parallel
      multiobjective steady-state genetic algorithm is applied to design
      environmentally benign and economically viable processes and to provide more
      accurate and uniform Pareto optimal solutions. In the last step a new
      visualization technique for illustrating multiple objectives and their design
      parameters on the same diagram is developed. Through these integrated steps the
      decision-maker can easily determine design alternatives with respect to his or
      her preferences. Most importantly, this technique is independent of the number of
      objectives and design parameters. As a case study, acetic acid recovery from
      aqueous waste mixtures is investigated by minimizing eight potential
      environmental impacts and maximizing total profit. After applying the systematic
      procedure, the most preferred design alternatives and their design parameters are
      easily identified.

PMID- 15871280
TI  - Efficient decomposition of environmentally persistent perfluorocarboxylic acids
      by use of persulfate as a photochemical oxidant.
AB  - Photochemical decomposition of persistent perfluorocarboxylic acids (PFCAs) in
      water by use of persulfate ion (S2O8(2-)) was examined to develop a technique to
      neutralize stationary sources of PFCAs. Photolysis of S2O8(2-) produced highly
      oxidative sulfate radical anions (SO4-), which efficiently decomposed
      perfluorooctanoic acid (PFOA) and other PFCAs bearing C4-C8 perfluoroalkyl
      groups. The major products were F- and CO2; also, small amounts of PFCAs with
      shorter than initial chain lengths were detected in the reaction solution. PFOA
      at a concentration of 1.35 mM (typical of that in untreated wastewater after an
      emulsifying process in fluoropolymer manufacture) was completely decomposed by a
      photochemical system with 50 mM S2O8(2-) and 4 h of irradiation from a 200-W
      xenon-mercury lamp. The initial PFOA decomposition rate was 11 times higherthan
      with photolysis alone. All sulfur-containing species in the reaction solution
      were eventually transformed to sulfate ions by this method. This method was
      successfully applied to the decomposition of perfluorononanoic acid contained in
      a floor wax solution.

PMID- 15871285
TI  - Dr. Joseph Massad and Millennium Productions: the future of dentistry will be
      televised.

PMID- 15871283
TI  - Life- cycle assessment in pesticide product development: methods and case study
      on two plant-growth regulators from different product generations.
AB  - Environmental assessments in pesticide product development are generally
      restricted to plant uptake and emissions of active ingredients. Life-cycle
      assessment (LCA) enables a more comprehensive evaluation by additionally
      assessing the impacts of pesticide production and application (e.g. tractor
      operations). The use of LCA in the product development of pesticides, in addition
      to the methods commonly applied, is therefore advisable. In this paper a
      procedure for conducting LCA in early phases of product development is proposed.
      In a case study, two plant-growth regulators from different product generations
      were compared regarding their application in intensive production of winter
      wheat. The results showed thatthe reduced emissions from active ingredients of
      the newer pesticide were compensated by higher impacts from the production
      process. The authors draw the conclusion that it is important to consider
      environmental objectives in the procurement of precursors, in addition to the
      classical goals of increasing the efficacy and reducing the nontarget effects of
      pesticides. Moreover, the case study showed that decisions based on uncertain
      results in early stages of product development may need to be revised in later
      stages, e.g. based on investigations of pesticides' effects on crop yield.

PMID- 15871284
TI  - Comment on "polybrominated diphenyl ethers contamination of united states food".

PMID- 15871286
TI  - Achieving quality esthetic dentistry and integrated comprehensive care with new
      generation techniques and materials.
AB  - BACKGROUND: Prosthodontics is the dental specialty responsible for diagnosis,
      rehabilitation and maintenance of patients with complex clinical conditions
      involving missing or deficient teeth and/or craniofacial tissues. The essence of
      the specialty is expert treatment planning. OVERVIEW/LITERATURE REVIEWED: In
      recent years, new approaches and technology have been introduced as a result of
      research performed in universities and by industry. The field of prosthodontics
      continues to evolve owing to a better understanding of the biology of the oral
      cavity and the introduction of new techniques and improved biomaterials.
      Improvements in periodontal and oral surgical techniques, implant procedures and
      materials, esthetic restorative materials, and jaw tracking recorders and
      articulators have led to enhanced functional and esthetic oral and maxillofacial
      prostheses. CONCLUSIONS AND CLINICAL IMPLICATIONS: The complexities of today's
      technical and clinical procedures and the higher expectations for more
      esthetically pleasing dentistry by the general patient population have placed a
      premium on teamwork involving general dentists, specialists and dental
      technicians.

PMID- 15871288
TI  - [Immunohistochemistry study of EGFR expression in head and neck squamous cell
      carcinoma].
AB  - EGFR is an important transmembrane receptor member of the family of tyrosine
      kinases, that translates signals from both outside and inside the cell and plays
      a key role in numerous proceses that affect tumour development, growth,
      progresion, differentiation, inhibition of apoptosis and metastasis.
      Immunohistochemistry studies have shown that 40-80% of head and neck squamous
      cell carcinomas express EGFR and it has been suggested as a potential independent
      prognostic parameter. The objective of this study is to evaluate by
      immunohistochemistry the expresi6n of EGFR in a series of Head and Neck Squamous
      Cell Carcinoma and correlate it to clinico-pathological features and prognostic
      significance. We investigated expression of EGFR in 44 samples. There was a high
      expression in 41% of the cases. Even if we have not found that the expression of
      EGFR correlated with the prognosis of these patients the presence of EGFR is very
      important because there are chemical agents or drugs that can inhibit its
      activity.

PMID- 15871287
TI  - [Experimental model of recurrent acute otitis media: morphological study of the
      cochlear damage using scanning electron microscopy].
AB  - We designed an experimental model of acute otitis media to study its effects in
      the hair cells of the organ of Corti. Thirty Sprague-Dawley rats were used, and
      divided into three groups. The rats from the first group were exposed to one
      episode of acute otitis media, the second group to two episodes and the third
      group were induced with three episodes of acute otitis media. After that, all
      cochleas were processed by specific surface specimen method. Finally, each organ
      of Corti was examined using scanning electron microscopy. Damage to hearing cells
      was compared between the three groups involved in the study. Significant great
      loss of sensory cells was found when the episodes of acute otitis media were
      repeated, in both turns of the cochlea: basal (alpha = 0.002) and distal (alpha =
      0.001). The results reported in this study indicate the importance of specialized
      treatment in children affected with recurrent acute otitis media to prevent
      cochlear damage.

PMID- 15871289
TI  - [Auditory-evoked brainstem response in a schwannoma of the VIIIth cranial nerve:
      an anatomophysiological and functional correlation. Our experience].
AB  - INTRODUCTION: Schwannomas are tumors charasteristically originated from the nerve
      sheath. They expande eccentrically from the nerve promoting a disturbance in the
      neural function either due to vascular compresion or to the effect of the tumor
      itself on the nerve, disturbance that can be evidenced with the Auditory-evoked
      Brainstem Response (ABR), fact that constituted the base for their diagnosis in
      the past. The new radiological techniques developed over the last decades have
      made possible an earlier diagnosis, and therefore changed their prognosis in
      terms of nerve function. Diagnosis is more certain today with these techniques so
      it could seem that ABR may not have any longer a role in the management of this
      condition. OBJECTIVE: To describe the most frequent ABR patterns in those
      patients suffering from acoustic schwannoma related to the size of the tumour and
      the remanent audition thresholds, and to determine the value of this test in our
      practice. MATERIAL AND METHODS: We describe the ABR features found in our series
      of 72 patients. Whose diagnosis was done between 1997 and 2003 in relation to the
      size of the tumour and the residual auditory function. RESULTS AND CONCLUSIONS:
      ABR has a good sensibility for detection of acoustic schwannoma. This sensibility
      decreases in small-sized tumours, specially in intracanalicular ones. ABR
      patterns do not relate to the size of the tumour but they do to the auditory
      function. The authors defend ABR to be a very valuable test due to the
      information and accesibility they provide.

PMID- 15871290
TI  - [Sentinel node in tumours of the lip and the oral cavity].
AB  - OBJECTIVES: This study shows the results obtained by the application of the
      sentinel node (SN) in oral and lip cancer and performs a lymphatic map of these
      tumours. PATIENTS AND METHOD: We prospectively studied 14 patients with lip and
      oral tumours, all of them N0. We injected colloidal particles of serum albumin
      labeled with Tc-99 peritumoraly and we located the SN intraoperatively. The SN
      was then sent for anatomopathological study. RESULTS: Sentinel node was
      identified in all of the patients. In 11 of them the sentinel node was negative
      for metastases and correctly predicted the status of the neck. In 3 patients the
      sentinel node was the only node that contained metastases. There were no false
      negatives. The sensibility of the technique was 100%. CONCLUSIONS: The results
      showed that this technique is a feasible method for tumours in these locations
      and can avoid neck dissections in N0 patients.

PMID- 15871291
TI  - [Functional outcomes of transoral laser surgery of supraglottic carcinoma].
AB  - OBJECTIVES: To analyse the functional outcome of patients with supraglottic
      carcinomas treated by transoral laser surgery. METHODS: The clinical records of
      55 patients who underwent transoral laser surgery were reviewed. Swallowing
      capacity, surgical complications, requirements for tracheotomies, percentage of
      decannulations, laryngeal paralysis, stenosis, aspiration associated pneumonia,
      time to remove the nasogastric tube and postsurgical stay in hospital were the
      studied variables. RESULTS: 52% of the patients had a normal or within functional
      limits swallowing performance. 18% suffered aspiration pneumonia. 13% developed a
      laryngeal stenosis. 7% suffered of laryngeal palsy. 18 tracheostomies were
      performed, of them 10 could be reverted. The mean time to remove the nasogastric
      tube was 9 days. The mean hospital stay was 23 days. CONCLUSIONS: The main
      functional advantages of transoral laser surgery for supraglottic carcinoma, when
      compared with the conventional approach, are a lower incidence of temporary
      tracheotomies, a faster removal of the nasogastric feeding tube, and a lower
      incidence of pharyngocutaneous fistulas (0%).

PMID- 15871292
TI  - [Frequency and risk factors of voice disorders among teaching staff of La Rioja,
      Spain. Clinical study: questionnaire, function vocal examination, acoustic
      analysis and videolaryngostroboscopy].
AB  - OBJECTIVE: To the analyse the risk factors of voice disorders among teaching
      staff of La Rioja, Spain. DESIGN: We carried out a transversal study of voice
      disorders in teaching staff of La Rioja (a random sample of 931 of 3.113
      teachers). PATIENTS: 527 teachers of random sample took part of study: 332 female
      (63%) and 195 male (37%). METHODS: All teachers filled in a standard
      questionnaire and posteriorly they underwent an, ENT and functional vocal cord
      examination, videolaryngostroboscopy and acoustic analysis with MDVP. RESULTS:
      The prevalence of voice disorders among La Rioja Teachers was 57%: 20% for
      organic lesions, 8% for chronic laryngitis and 29% for functional disorders.
      Women compared with men did not have a higher prevalence of voice disorders (p >
      0.05) (OR: 1.138). Professional and personal factors as well as classroom
      atmosphere were studied. The most relevant factors in the pathological group were
      previous vocal pathology, laryngeal surgery, gastroesophageal reflux and,
      classroom dryness and smoking habits. CONCLUSIONS: The most relevant factor of
      voice disorders in teaching professional is the vocal overwork during their job.
      It is advisable to carry out a clinical evaluation of all the future teachers in
      their educational programs.

PMID- 15871293
TI  - [Dehiscence of the superior semicircular canal: report of a case and bibliography
      review].
AB  - We present a case of deficiency of the superior semicircular canal (SSCD) in a 37
      years old patient that came to us because of episodes of subjective vertigo in
      response to intense sounds (Tullio phenomenon). The audiometry,
      electronistagmography, timpanometry and stapes reflexes were normal and the
      fistula test was negative. The CT scan showed an absence of bone overlying the
      superior semicircular canal (SSC) of the right ear and the left ear was normal.
      When both ears were exposed to intense sounds, only the right one presented
      vertigo was, without nystagmus.

PMID- 15871294
TI  - [ENT expression of hypohidrotic ectodermal dysplasia].
AB  - Hypohidrotic Ectodermal Dysplasia (HED) is a rare recesive genetic disease linked
      to chromosome X whose main characteristic is the reduction of sweat glands,
      leading to a deficient sweating and an increase in body temperature. In HED
      mainly the ectodermal structures are involved such, as epidermis and its anexes
      (hair and nails), although non-ectodermal tissue may also become involved.
      Otolaryngologicalmanifestations are related to hypoplasia of the mucous glands of
      the upper aerodigestive tract, as chronic infections, like rhinitis, pharyngitis,
      bronchitis and otitis, and also epistaxis, dysphagia, anodontia and, ozena, among
      others. A case of a young adult male affected with HED who is referred to the
      Otolaryngology Departament with a history of chronic pharyngitis and ozena, is
      presented and the literature reviewed.

PMID- 15871295
TI  - [Hearing loss measurement. An equation for a rapid calculation].
AB  - Hearing loss must be easily calculated by mean of the rules of actual legislation
      on handicap. It is just necessary to know the hearing thresholds for 500, 1000,
      2000 and 4000 Hz tones. Calculation of a linear regression equation allows to
      obtain quickly hearing loss average from these thresholds.

PMID- 15871296
TI  - Modality-specificity effects in priming of visual and auditory word-fragment
      completion.
AB  - In this study, the researchers examined modality-specificity effects in priming
      of visual and auditory word-fragment completion by the presentation of visual or
      auditory primes. In 2 experiments, within-modality priming and cross-modality
      priming were observed, with greater priming observed in the within-modality
      conditions. The prime was presented in a word list in Experiment 1 and either
      presented or inferred in priming sentences in Experiment 2. Inferring a target
      that was not actually presented in the sentences resulted in priming of fragment
      completion but not in modality specificity. These results, coupled with
      comparisons to explicit cued fragment completion, support the interpretation that
      priming of word-fragment completion is owing to both a perceptual and a
      nonperceptual component. This latter component may be different than the
      conceptual processes used for explicit memory, which did show modality
      specificity for inferred targets.

PMID- 15871297
TI  - General versus gender-specific attributes of the psychology major.
AB  - In the present study, the authors extended the search for general and gender
      specific factors associated with the selection of psychology as a college major
      by using the Family Environment Scale (FES; R. H. Moos & B. S. Moos, 1994) and
      Coolidge Axis II Inventory (CATI; F. L. Coolidge & M. M. Merwin, 1992). The
      findings were restricted to one general (Schizoid) and one gender-specific (Self
      Defeating) set of personality traits that seemed to be associated with the
      selection of a college major. The intuitive role of many presumed gender-specific
      factors (e.g., women are more open to discussing personal problems with others)
      may prove difficult to establish empirically.

PMID- 15871298
TI  - Serial position effects in recall of television commercials.
AB  - Does the position of a television commercial in a block of commercials determine
      how well it will be recalled? The findings of naturalistic studies can be
      affected by uncontrolled presentation, viewing, and retention variables. In the
      present article, college students viewed lists of 15 commercials in a laboratory
      simulation and recalled the product brand names. In an immediate test, the first
      commercials in a list were well recalled (a primacy effect), as were the last
      items (a recency effect), in comparison with the recall of middle items. In an
      end-of-session test, the primacy effect persisted, but the recency effect
      disappeared. Embedding lists within a television program again produced better
      recall of the first items during end-of-session tests of recall and recognition.
      These results offered convergent validity for the naturalistic studies of
      commercial memory, and they supported the usefulness of combining laboratory and
      field methods to answer questions about everyday memory.

PMID- 15871299
TI  - Confidence judgments by humans and rhesus monkeys.
AB  - Researchers have begun to evaluate animals' metacognitive capacities. Continuing
      this evaluation, the present authors asked whether monkeys could use the analog
      of a confidence-rating scale to judge retrospectively their accuracy in a
      psychophysical discrimination. Monkeys and human participants classified stimuli
      as dense or sparse without feedback. Then, they made a secondary confidence
      judgment by choosing responses that risked different levels of timeout but could
      earn different levels of reward. Human participants were instructed to use these
      responses to express levels of confidence. They used 2- and 3-level confidence
      rating scales appropriately. Monkeys used the 2-level scale appropriately-
      especially one who performed almost identically to humans. Neither monkey used
      the 3-level scale as the humans did. These studies place humans and animals for
      the first time in the identical risk-taking situation that collects declarative
      confidence judgments from humans. They demonstrate the first retrospective
      reports of uncertainty by non-human primates while also suggesting their limits
      in this area.

PMID- 15871300
TI  - Mice selectively bred for open-field thigmotaxis: life span and stability of the
      selection trait.
AB  - In 2 experiments, the authors examined 69 mice selectively bred for high or low
      levels of open-field (OF) thigmotactic behavior (high open-field thigmotaxis
      [HOFT] and low open-field thigmotaxis [LOFT], respectively). They found that the
      strains differed in defecation during the 60-min exposure to the OF. Furthermore,
      the strains differed with regard to their life spans: The more thigmotactic HOFT
      mice lived longer than the LOFT mice. The strains were not differentiated by food
      intake or excretion. The strain difference in thigmotaxis was not age dependent,
      and it persisted in the home-cage condition as well. Neither the location (center
      or wall) of the starting point nor the shape (circular or square) of the OF arena
      affected the difference in wall-seeking behavior between the two strains. The
      authors concluded that the difference in thigmotaxis (or emotionality) between
      the HOFT and LOFT mice is a stable and robust feature of these animals.

PMID- 15871301
TI  - Behavioral effects of stimulation of the medial amygdala in the male rat are
      modified by prior sexual experience.
AB  - Researchers have found that stimulation of the medial nucleus of the amygdala
      (MeA) in male rats increases appetitive copulatory behavior directed toward an
      anestrous female but suppresses copulation with an estrous female (C. P. Stark et
      al., 1998). The objective in the present study was to determine if the behavioral
      change produced by stimulation of the MeA was dependent on chemical and/or visual
      cues from the conspecific. The author reports that electrical stimulation of the
      MeA in male rats increased the frequency of mounting and investigative behavior
      directed toward a male conspecific. However, these effects were limited to those
      subjects that had no prior sexual experience. Results are discussed in terms of
      possible experience-dependent alterations in neural response patterns within the
      MeA and related areas.

PMID- 15871302
TI  - The importance of cultural considerations in the promotion of ethical research
      with human biologic material.
AB  - Although ethical consideration has been given to a wide variety of issues that
      arise in the collection and storage of human biologic material for research,
      little attention has been focused on the ethical implications of the diverse
      cultural meanings often associated with these materials. We explore the rich
      social meanings of the placenta across cultures and contrast these meanings with
      the assumption that the placenta is typically considered waste tissue that may
      find value in biomedical research. We suggest that the incorporation of
      sensitivity to the cultural meanings people give human biologic material and the
      use of empirical research, where necessary, to delineate these meanings should
      enhance the ability to craft and conduct ethically appropriate research.

PMID- 15871303
TI  - Clinical evaluation of urinary excretion of liver-type fatty acid-binding protein
      as a marker for the monitoring of chronic kidney disease: a multicenter trial.
AB  - To confirm the clinical usefulness of the measurement of urinary liver-type fatty
      acid-binding protein (L-FABP) in chronic kidney disease (CKD), we carried out a
      multicenter trial. Clinical markers were measured in patients with nondiabetic
      CKD (n = 48) every 1 to 2 months for a year. We divided patients retrospectively
      into progression (n = 32) and nonprogression (n = 16) groups on the basis of the
      rate of disease progression, then assessed several clinical markers. Initially
      creatinine clearance (Ccr) was similar in the 2 groups; however, the urinary L
      FABP level was significantly higher in the former group than in the latter (111.5
      vs 53 microg/g creatinine, P < .001). For the monitoring CKD, we set the cutoff
      values for urinary L-FABP and urinary protein at 17.4 microg/g creatinine and 1.0
      g/g creatinine, respectively. Urinary L-FABP was more sensitive than urinary
      protein in predicting the progression of CKD (93.8% and 68.8%, respectively).
      However, urinary protein showed greater specificity than did urinary L-FABP
      (93.8% and 62.5%, respectively). Over time, the progression of CKD tended to
      correlate with changes in urinary L-FABP (r = - .32, P < .05), but not in urinary
      protein (r = .18, not significant). The dynamics of urinary protein differed from
      that of urinary L-FABP, which increased as Ccr declined. Urinary L-FABP is more
      sensitive than urinary protein in predicting the progression of CKD. Urinary
      excretion of L-FABP increases with the deterioration of kidney function. Urinary
      L-FABP is therefore a useful clinical marker in the monitoring of CKD.

PMID- 15871304
TI  - Chemoprevention of hepatocellular carcinoma: use of tamoxifen in an animal model
      of hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) is common worldwide and growing in importance in
      the West. HCC often occurs against a background of liver disease, tends to
      present at an advanced stage, and has a poor prognosis, suggesting that it is an
      ideal target for chemoprevention. We sought to identify in an animal model
      chemopreventive agents for HCC that might be tested in human subjects. To this
      end, we induced liver tumors by injecting ethyl-nitrosourea in 6-week-old male
      B6C3F1 mice. Two chemopreventive agents were administered over a period of 60
      weeks: tamoxifen (420 mg/kg feed) and a retinoid, 13-cis-retinoic acid (200 mg/kg
      feed). Animals were killed at 60 weeks and their livers examined for HCC and
      premalignant lesions. All liver lesions (altered foci, adenomata, HCC) occurred
      significantly less frequently in the tamoxifen-treated group than the group given
      only ethylnitrosourea (HCC developed in 2 of 47 (4%) vs 11 of 44 (25%); P <
      .001). On the other hand, retinoic acid appeared to increase the number of liver
      tumors, and in 2 animals angiosarcoma developed. Tamoxifen significantly
      decreased the incidence of chemical hepatocarcinogenesis in this model,
      suggesting an important role for estrogens in the pathogenesis of HCC and
      suggesting that it should be tested in human beings as a chemopreventive agent
      against HCC.

PMID- 15871305
TI  - Treatment of Wilson's disease with zinc from the time of diagnosis in pediatric
      patients: a single-hospital, 10-year follow-up study.
AB  - Wilson's disease (WD) is an inherited disorder of copper metabolism characterized
      by a failure of the liver to excrete copper, leading to its accumulation in the
      liver, brain, cornea, and kidney, with resulting chronic degenerative changes. It
      is generally accepted that "presymptomatic" patients--in whom WD is diagnosed in
      childhood and who are defined as those who, although still asymptomatic, do have
      liver disease, as indicated by increased serum concentrations of transaminases-
      should be treated prophylactically. Here we report our results in 22 children
      treated with continuous oral zinc therapy for 10 years. Zinc sulfate was
      administered at a dosage of 25 mg elemental zinc twice a day until the age of 6
      years, 25 mg three times a day between the ages of 7 and 16 years or until the
      child attained a body weight of 125 lb, and 50 mg three times a day thereafter.
      Five years after the start of zinc treatment, we noted highly significant
      decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST),
      and urinary copper excretion, but white blood cell counts did not vary
      significantly. Six of 22 patients continued to demonstrate greater-than-normal
      ALT concentrations and only 1 patient demonstrated an ALT concentration more than
      1.5 times the upper normal limit. Further decreases in ALT, AST, and urinary
      copper excretion were observed at the end of the 10-year follow-up, but these
      decreases were not statistically significant. Only 1 patient continued to
      demonstrate abnormal ALT levels. Again, white blood cells showed no significant
      variations. All histologic scores (steatosis, inflammation, and fibrosis) were
      significantly decreased after treatment. Hepatic copper content was also
      significantly decreased, although it remained higher than normal in all patients.
      The removal of toxic copper was confirmed by disappearance of Kayser-Fleischer
      rings in 3 patients. Zinc did not have adverse effects on growth. The efficacy of
      zinc in WD in presymptomatic pediatric patients has been established in previous
      studies, and our study adds considerably to the earlier findings because it
      includes a large number of very young children, as many as 11 younger than 6
      years and 20 younger than 10. The excellent clinical results in all patients,
      coupled with the improvement in hepatic histologic findings in the vast majority,
      indicate convincingly that zinc treatment can control the disease effectively and
      safely, preventing its progression over the course of 10 years. Histologic
      findings reportedly improved in 3 patients treated in an earlier study, but our
      data are numerically much more relevant. Notably, histologic study of the liver
      revealed that copper concentration was reduced by treatment, suggesting that oral
      zinc was able not only to prevent further accumulation of copper but also to
      promote, at least in part, the depletion of its stores. The lack of adverse
      effects of zinc on growth suggests that our patients received enough anticopper
      therapy to prevent damage resulting from copper toxicity but an adequate amount
      of copper for proper growth and development. In conclusion, our findings indicate
      that zinc is the treatment of choice in presymptomatic pediatric patients with
      WD.

PMID- 15871306
TI  - Insulin alters nuclear factor-lambdaB and peroxisome proliferator-activated
      receptor-gamma protein expression induced by glycated bovine serum albumin in
      vascular smooth-muscle cells.
AB  - In both type 2 diabetes and insulin-resistance syndromes, hyperglycemia and
      advanced glycation end products (AGEs) activate the transcription factor nuclear
      factor-kappaB (NF-kappaB) through a mechanism that partly involves the generation
      of reactive oxygen species (ROS). The contribution of hyperinsulinemia in this
      sequence has not been completely elucidated. In this work we investigated the
      actions of insulin and PPAR-gamma on the stimulation by AGEs of NF-kappaB protein
      expression in cultured aortic vascular smooth-muscle cells (VSMCs) from non
      insulin-dependent diabetic rats and nondiabetic rats. The expression of proteins
      was evaluated with the use of Western immunoblotting. Incubations (24 hours) of
      VSMCs with 10 to 100 microg/mL glycated bovine serum albumin (AGE- BSA) increased
      NF-kappaB protein expression in both models. PPAR-gamma protein expression was
      only enhanced at concentrations of 500 to 1000 microg/mL (AGE-BSA). In the
      presence of insulin (10-100 nmol/L), the stimulation of NF-kappaB protein
      expression by AGE-BSA (100 microg/mL) was decreased, whereas the expression of
      PPAR-gamma, protein was enhanced. 15-Deoxyprostaglandin J2, a direct activator of
      PPAR-gamma, decreased AGE-BSA-stimulated NF-kappaB expression. These findings
      suggest that insulin decreases the incidence of alterations in VSMCs induced by
      AGEs through the reduction of NF-kappaB and an increase in PPAR-gamma protein
      expression (as far as the model could be extrapolated to in vivo situations).
      These data may help justify current therapeutic approaches involving the use of
      insulin and PPAR-gamma agonists.

PMID- 15871307
TI  - Increased plasma anti-Xa activity and recovery of heparin from urine suggest
      absorption of orally administered unfractionated heparin in human subjects.
AB  - Although heparin is not generally administered orally, the results of studies
      involving rats suggest that heparin is absorbed, with low levels in plasma but
      extensive distribution to the endothelium. To determine whether evidence of
      absorption after oral administration can also be demonstrated in human subjects,
      we administered unfractionated porcine heparin in a single dose of 1000 U/kg to 6
      healthy human subjects. Plasma anticoagulant activity was monitored between 5
      minutes and 72 hours after administration, and chemical heparin concentrations
      were determined in 24-hour urine samples for as long as 120 hours after
      administration. Plasma anticoagulant activity, determined by anti-Xa activity,
      increased as soon as 5 minutes after heparin administration, peaked at 120
      minutes, and was still increased 72 hours after administration. Values were
      significantly greater 15 minutes to 48 hours after administration compared with
      values before administration (paired t test). Mean activated partial
      thromboplastin time and Heptest values in subjects given heparin were greater
      than those in controls 15 and 30 minutes and 5 to 120 minutes after
      administration, respectively. Heparin was recovered from urine as long as 120
      hours after administration (the latest time point at which samples were
      collected); greater amounts were excreted between 48 and 120 hours than before 48
      hours. Recovery from both plasma and urine suggest that unfractionated heparin
      administered orally is absorbed in human subjects, is widely distributed, and is
      found in the body at least 120 hours after administration. Because heparin is
      readily bound to endothelium, recovery from plasma and urine likely reflect
      considerable amounts with endothelium, as has been observed in other species.

PMID- 15871308
TI  - Nocardiosis in persons with human immunodeficiency virus infection, transplant
      recipients, and large, geographically defined populations.
AB  - To quantify the risk of nocardiosis in various populations, I systematically
      reviewed articles published between 1966 and 2004. The incidence of nocardiosis
      in 3 large, geographically defined populations ranged from 0.35 to 0.4 cases per
      10(5) persons year. In contrast, the incidence of nocardiosis among people with
      human immunodeficiency virus (HIV) infection or acquired immunodeficiency
      syndrome (AIDS) in 1 study was 53 nocardiosis cases per 10(5) persons x year,
      approximately 140 times greater than that in the geographically defined
      populations. The frequency of nocardiosis cases in 4 populations of HIV-infected
      people averaged 608 cases per 10(5) persons. The incidence of nocardiosis in bone
      marrow-transplant recipients at 1 hospital was 128 cases per 10(5) persons x
      year, an incidence approximately 340 times greater than that in the
      geographically defined populations and in the same range as in HIV-infected
      people. The frequency of nocardiosis in 21 series of cases in recipients of a
      variety of transplanted organs averaged 1122 cases per 10(5) persons. These
      estimated incidence rates are imprecise because they were not collected through
      prospective surveillance systems, but the estimates for the 3 groups were
      internally consistent and provide useful information for clinicians.

PMID- 15871309
TI  - Kibuka's umbilical cord.

PMID- 15871310
TI  - Histologic and ultrastructural analysis of ultraviolet B laser and light source
      treatment of leukoderma in striae distensae.
AB  - BACKGROUND: Lasers and light sources emitting ultraviolet B (UVB) irradiation
      have been shown to repigment striae distensae. OBJECTIVE: The purpose of this
      study was to analyze the histologic and ultrastuctural changes seen after UVB
      laser- or light source-induced repigmentation of striae distensae. METHODS: Ten
      subjects with hypopigmented striae were selected. Five subjects were treated with
      an XeCl excimer UVB laser, and five subjects were treated with a UVB light
      device. Six months after the final treatment, the biopsies were evaluated for
      both standard and electron microscopic changes in melanocytes. RESULTS: Analyses
      of biopsied skin after treatment with both the UVB laser and light source showed
      increased melanin content, hypertrophy of melanocytes, and an increase in the
      number of melanocytes in all patients. CONCLUSIONS: Repigmentation of striae
      distensae with either a UVB laser or light source is due to an increase in
      melanin pigment, hypertrophy of melanocytes, and an increase in melanocytes.

PMID- 15871311
TI  - Laser-doppler examination shows high flow in some common telangiectasias of the
      lower limb.
AB  - BACKGROUND: The accepted pathophysiology of telangiectasias is reflux from
      superficial or deep veins. There are physical signs and scientific findings that
      do not fit this theory but support the possibility of arteriovenous (AV) shunt
      origin. OBJECTIVE: If there is a higher flow in spider veins than in the
      surrounding skin, it means that AV shunts participate in the circulation of the
      telangiectasia. On the other hand, slow flow indicates reflux as the etiologic
      factor. METHOD: Telangiectasias and the surrounding skin of 22 legs of 19
      patients were examined with laser-Doppler equipment. RESULTS: The probe over the
      spider vein found a higher flow value (average 28.2 perfusion units [PU]) than in
      the surrounding skin (15.6 PU) in 13 limbs, but it was significantly higher only
      in 5 cases. In 9 limbs, the flow was slower. CONCLUSION: We interpret the higher
      flow values as a consequence of open AV shunts. This means that AV shunt
      pathophysiology was present in some of our cases.

PMID- 15871312
TI  - Gene expression profiles in varicose veins using complementary DNA microarray.
AB  - BACKGROUND: There has been little information reported about the genetic event
      concerning the pathophysiology of varicose vein (VV). OBJECTIVES: The purpose of
      this study was to examine the differentiation of gene expression in the wall of
      VV using complementary deoxyribonucleic acid (cDNA) microarrays. METHODS: The
      study was performed with four pairs of VVs and control veins (CVs). cDNA
      specimens of VVs were prepared from the ribonucleic acid-isolated VVs of patients
      who underwent venous obliteration, using radiofrequency, as well as from CVs of
      those who underwent aortocoronary bypass grafting. Each set of VVs and CVs was
      hybridized with high-density microarray containing 3,063 human cDNAs. The finding
      of microarray hybridization were scanned, analyzed, and classified with the
      cluster program. RESULTS: Among 3,063 cDNA clones, 82 genes were up-regulated in
      VVs, and some of the up-regulated genes, which were detected by cDNA microarray,
      including transforming growth factor 3-induced gene (BIGH3), tubulin, lumican,
      actinin, collagen type I, versican, actin, and tropomyosin, belonged to
      extracelluar matrix molecules, cytoskeletal proteins, or myofibroblasts.
      CONCLUSIONS: Many up-regulated genes were found in Ws by applying cDNA
      microarray. These gene profiles suggested a pathway associated with fibrosis and
      that wound healing might be related to the pathophysiology of VVs.

PMID- 15871314
TI  - Does laser inactivate botulinum toxin?
AB  - BACKGROUND: Botulinum toxin is a popular and effective treatment for dynamic
      rhytids. It is a neurotoxic protein complex that exerts its effect by inhibiting
      acetylcholine release at the presynaptic neuromuscular junction. Nonablative
      resurfacing treatments have also become well liked by patients and physicians
      owing to the minimal downtime associated with treatment. Currently, same-day
      nonablative laser treatments are performed prior to botulinum toxin injection
      owing to the concern that the laser may inactivate it. On occasion, it may be
      desirable to perform nonablative laser after the botulinum toxin has been
      injected (ie, patient afterthought, scheduling concern). OBJECTIVE: To determine
      whether the use of nonablative rejuvenation laser or intense pulsed light (IPL)
      immediately following botulinum toxin injections has any effect on the efficacy
      of the botulinum toxin treatment. METHODS: Nineteen subjects received botulinum
      toxin injections to either the glabellar or crow's-feet areas. One side of the
      treated glabellar or periorbital area was treated with either VBeam laser
      (Candela, Wayland, MA, USA), SmoothBeam laser (Candela), CoolGlide laser (Cutera,
      Brisbane, CA, USA), or an IPL or radiofrequency (RF) device within 10 minutes of
      botulinum toxin injection. Pretreatment and 2-week post-treatment photographs
      were compared. RESULTS: No decrease in the efficacy of botulinum toxin
      denervation was observed when glabellar or perioral areas were treated with VBeam
      laser, SmoothBeam laser, CoolGlide laser, or an IPL or RF device within 10
      minutes of botulinum toxin injection. CONCLUSION: Patients may be treated with
      several nonablative lasers and IPL or RF devices immediately after botulinum
      toxin injection without loss of efficacy or other apparent untoward effect.

PMID- 15871313
TI  - Direct comparison of EMLA versus lidocaine for pain control in Nd:YAG 1,064 nm
      laser hair removal.
AB  - BACKGROUND: Laser hair removal is an effective therapy for the treatment of
      hirsutism, hypertrichosis, and pseudofolliculitis barbae. Although side effects
      are uncommon, pain is described by most patients undergoing long-pulsed
      neodymium:yttrium-aluminum-garnet (Nd:YAG) 1,064 nm laser therapy. OBJECTIVES: To
      compare the efficacy of topical eutectic mixture of local anesthetics (EMLA)
      versus topical lidocaine (LMX) in pain control for Nd:YAG 1,064 nm laser hair
      removal. METHODS: Sixty-four patients were enrolled in a double-blind randomized
      study over a 6-month period. Each patient had half of the treatment area covered
      with EMLA and the other half with LMX 30 minutes prior to treatment. Neither was
      applied under occlusion. Immediately following their treatment session, patients
      completed a visual analog pain scale. RESULTS: There was no statistically
      significant difference in pain control between EMLA and LMX. However, female test
      subjects demonstrated lower pain scores than male test subjects. CONCLUSIONS:
      Nd:YAG 1,064 nm laser hair removal is a painful procedure. Topical anesthetics
      have been proven to reduce pain for laser hair removal. There is no statistically
      significant difference between the two most commonly used topical anesthetics for
      pain control in laser hair removal. Therefore, cost and minimizing potential side
      effects should guide the physician in selecting the appropriate anesthetic.

PMID- 15871315
TI  - Prospective open-label study of botulinum toxin type A in patients with axillary
      hyperhidrosis: effects on functional impairment and quality of life.
AB  - BACKGROUND: Patients with primary axillary hyperhidrosis experience substantial
      functional impairment and reduced health-related quality of life (HRQOL). Few
      studies have comprehensively evaluated the effects of botulinum toxin type A
      (BoNT-A) on these symptoms. OBJECTIVE: To prospectively assess the effects of
      BoNT-A on functional impairment associated with primary axillary hyperhidrosis.
      METHODS: Patients treated with BoNT-A 50 U per axilla at baseline were assessed 4
      and 12 weeks later. Outcome measures included functional impairment as assessed
      by the Hyperhidrosis Disease Severity Scale and the Hyperhidrosis Impact
      Questionnaire and dermatology-specific HRQOL as assessed by the Dermatology Life
      Quality Index. RESULTS: At weeks 4 and 12 after BoNT-A treatment, 85% and 90% of
      patients achieved the a priori definition of treatment responder. Patients
      reported less occupational and emotional impairment, spent less time managing
      their hyperhidrosis, and had fewer difficulties in social situations. Adverse
      events were uncommon (5.5%), were mild, and did not require treatment. At study
      end, 53% of patients reported no dermatology-specific HRQOL impairment and 90%
      were satisfied with treatment. CONCLUSIONS: Significant, meaningful, rapid, and
      durable reductions in disease severity and functional impairment, as well as
      improvements in HRQOL, were seen following BoNT-A treatment. BoNT-A was safe and
      well tolerated, producing high levels of patient satisfaction.

PMID- 15871316
TI  - Dose-ranging study of botulinum toxin type A in the treatment of glabellar
      rhytids in females.
AB  - OBJECTIVE: To compare the efficacy, safety, and duration of effect of four doses
      of botulinum toxin type A in the treatment of glabellar rhytids in females.
      DESIGN: Double-blind, randomized, parallel-group, dose-ranging trial followed by
      an open-label extension. SETTING: Private dermatologic clinic. SUBJECTS: Eighty
      female subjects with moderate to severe wrinkles at maximum frown entered the
      study. The first 40 subjects completing the double-blind phase entered the open
      label extension. INTERVENTION: Random administration of 10, 20, 30, or 40 U
      botulinum toxin type A in divided doses. Open-label trial: 30 U botulinum toxin
      type A at the same sites in divided doses. MAIN OUTCOME MEASUREMENTS: Trained
      observer and subject assessments of wrinkle severity at maximum frown and repose
      using the Facial Wrinkle Scale (0 = none to 3 = severe), subject satisfaction,
      and adverse events. Follow-up monthly for up to 1 year postinjection. RESULTS:
      Relapse rates and responder rates revealed benefits lasting 3 to 6 months or
      longer. Objectively, 10 U of botulinum toxin type A was significantly less
      effective than 20, 30, or 40 U. The relapse rate at 4 months was significantly
      higher in the 10 U group (83%) versus 40, 30, or 20 U (28%, 30%, and 33%,
      respectively). Subject satisfaction was high in all groups. Duration of effect
      and response rates were sustained during the open-label extension. Adverse
      effects were mild and infrequent. CONCLUSION: Twenty to 40 U botulinum toxin type
      A doses were significantly more effective at reducing glabellar lines than 10 U.
      Most subjects experienced benefits for 3 to 4 months; some subjects demonstrated
      effect for up to 12 months.

PMID- 15871317
TI  - LRIG-1 provides a novel prognostic predictor in squamous cell carcinoma of the
      skin: immunohistochemical analysis for 38 cases.
AB  - BACKGROUND: The LRIG-1 gene (formerly LIG-1) encodes a type 1 transmembrane
      glycoprotein with an extracellular region of 15 leucine-rich repeats and 3
      immunoglobulin-like domains. LRIG-1 interacts with ErbB receptors, down
      regulating the downstream signals. Because ErbB signaling is disrupted in
      cutaneous squamous cell carcinoma (SCC), we examined LRIG-1 expression in
      cutaneous SCC. OBJECTIVE: To analyze the differential expression of LRIG-1 and to
      investigate whether LRIG-1 is useful as a prognostic indicator in SCC of the
      skin. METHODS: LRIG-1 expression in 38 cases of cutaneous SCC patients was
      examined by immunohistochemistry. RESULTS: LRIG-1 expression was highest in well
      differentiated lesions of cutaneous SCC. The cases studied here were categorized
      into 23 cases (60.5%) of high expression and 15 cases (39.5%) of low expression
      of LRIG-1. There was a significant correlation (p = .000018) of LRIG-1 expression
      intensity of tumor cells with histologic differentiation of SCC. Furthermore, we
      found a significant inverse correlation with metastatic rate (p = .02). When the
      overall survival of SCC patients was statistically compared between high and low
      LRIG-1 expression groups, a significant survival benefit for the patients in the
      former group was found (p = .03). CONCLUSION: LRIG-1 expression is an excellent
      candidate for a prognostic indicator of cutaneous SCC.

PMID- 15871318
TI  - Tapping into the influence of keratinocyte allografts and biocenosis on healing
      of chronic leg ulcers: split-ulcer controlled pilot study.
AB  - BACKGROUND: Cultured keratinocytes may represent an alternative therapy aiming at
      boosting leg ulcer healing. There is no evidence-based study comparing
      objectively the healing rate of split-ulcer portions covered or not covered by
      cultured keratinocytes. OBJECTIVE: To assess the effect of cultured keratinocytes
      on the healing rate of leg ulcers. METHOD: Five applications of fresh (cela,
      XCELLentis, Ghent, Belgium) or frozen (CryoCeal, XCELLentis) cultured allogeneic
      keratinocytes were performed at weekly intervals to treat large leg ulcers (mean
      diameter > 5 cm) in four patients. A split-ulcer study was designed to secure a
      control area covered only by petrolatum gauze. Clinical, planimetric,
      bacteriologic, and immunohistologic assessments of the keratinocyte-treated and
      control parts of the ulcers were performed. RESULTS: Compared with controls,
      planimetry revealed a beneficial effect afforded by cryopreserved cultured
      keratinocytes on the ulcer healing rate of two of four ulcers (+12 and 81%). The
      healing effect was obtained on the ulcers associated with the lowest bacterial
      load. Cultured keratinocytes did not qualitatively and quantitatively modify the
      ulcer biocenosis. They did not affect the number of any type of inflammatory
      cells present in the granulation tissue (type I dermal dendrocytes, macrophages,
      T lymphocytes, granulocytes). No specific side effect of cultured keratinocytes
      was evidenced. CONCLUSION: In this small case series, it appears that cultured
      allogeneic keratinocytes may be helpful in the healing process of venous leg
      ulcers. However, a clean wound with reduced bacterial load seems to be the
      prerequisite condition for obtaining a beneficial effect.

PMID- 15871319
TI  - Comparison of minipunch grafting versus split-skin grafting in chronic stable
      vitiligo.
AB  - BACKGROUND: Minipunch grafting (MPG) and split-skin grafting (SSG) are common
      outpatient procedures for the surgical treatment of chronic stable vitiligo.
      However, there is a paucity of literature comparing the two procedures by the
      same group of investigators. OBJECTIVE: To compare the two techniques in patients
      with chronic stable localized vitiligo. METHODS: Sixty-four patients with stable
      vitiligo of 6 months duration were randomized into two groups to be taken up for
      MPG or SSG in a representative patch followed by PUVAsol therapy for 3 months.
      They were evaluated 3 months postoperatively for the degree of repigmentation and
      side effects. RESULTS: In the MPG group, 644 grafts, 2.5 mm in size, were placed
      on a total vitiliginous area of 521.25 cm2, whereas in the SSG group, 153 grafts
      covered a 1,489 cm2 recipient area. Three months postoperatively, in the first
      group, 15 cases (44.1%) showed very good to excellent (> 75%) repigmentation
      compared with 25 cases (83.3%) in group 2. Following MPG, 81 grafts (12.57%) were
      rejected. Cobblestoning was the main side effect, occurring in 13 cases (38.23%),
      and a variegated appearance was observed in 7 (20.58%) patients. The
      complications noted after SSG were achromic fissuring in four (13.3%) cases,
      graft contracture in four grafts (2.61%) in three patients, and rejection of
      seven grafts (4.57%) in one case; tire-pattern appearance in two patients (6.6%);
      milia formation in four (13.3%) patients; and depigmentation of the grafts in two
      (6.6%) cases. In both groups, superficial scarring was noted at the donor site in
      all cases, whereas hypertrophic scarring occurred in 3 (10%) patients after SSG.
      CONCLUSION: SSG carries a distinct advantage over MPG in producing excellent
      cosmetic matching over larger areas using fewer grafts, especially over the face
      and extremities.

PMID- 15871320
TI  - Fluorodeoxyglucose positron emission tomography in cutaneous squamous cell
      carcinoma: retrospective analysis of 12 patients.
AB  - BACKGROUND: Whole-body 18F-fluorodeoxyglucose positron emission tomography (FDG
      PET) has been used for whole-body imaging modality in detecting malignancy in
      clinical oncology. However, only a few reports of FDG PET in skin cancers have
      been described, except for melanoma and lymphoma. OBJECTIVE: To report on the
      usefulness of FDG PET as a baseline workup study for patients with cutaneous
      squamous cell carcinoma (SCC). METHODS: There were 12 cases of SCC (9 cases with
      high-risk SCC). Of the 12, FDG PET was performed for staging in 11 patients and
      for restaging in 1 patient 1 year after wide excision. RESULTS: Primary lesions
      were detected in nine cases (83.3%), lymph node involvement in three cases
      (25.0%), and distant. organ (lung) involvement in one case (8.3%). In one patient
      whose primary lesion was positive, stomach cancer with involvement of adrenal
      glands, omentum, and lymph nodes was incidentally detected. All of the patients
      with high-risk SCC showed FDG uptakes of the primary lesions, and the patients
      with FDG uptakes in lymph nodes and distant organ had high-risk SCC. CONCLUSION:
      There have been no comparative studies on the cost-effectiveness between sentinel
      lymph node biopsy and FDG PET in SCC patients. However, considering the
      noninvasiveness and thoroughness in checking the whole body, including distant
      organs, FDG PET may have clinical value as a baseline workup study for patients
      with high-risk SCC.

PMID- 15871321
TI  - Nasalis island pedicle flap in nasal ala reconstruction.
AB  - BACKGROUND: Defects of the nasal ala can be difficult to repair in a one-stage
      procedure. We describe a laterally based nasalis myocutaneous island pedicle flap
      to repair small but deep defects of the superior nasal ala. OBJECTIVE: To
      describe a single-stage flap for repair of small defects on the nasal ala that
      confines the repair to one cosmetic unit. METHODS: We discuss the anatomy of the
      flap and illustrate the method of placing the flap. RESULTS: We present several
      case examples and discuss potential applications of the flap. We also discuss the
      flap's limitations by citing an example of necrosis. CONCLUSIONS: The nasalis
      myocutaneous island pedicle flap for repair of nasal alar defects is a new
      application of a one-stage procedure that yields excellent functional and
      cosmetic results. Knowledge of the limitations and the anatomy of the flap is
      crucial for a good outcome.

PMID- 15871322
TI  - Transcutaneous face-lift.
AB  - BACKGROUND: Face-lifting can result in a number of complications. A mini-invasive
      technique is now presented. OBJECTIVE: To perform face-lifting as a simple,
      quick, and mini-invasive ambulatory approach in patients requiring mild to
      moderate lift. MATERIALS AND METHODS: Using a Khawaja-Hernandez or Keith needle
      and polypropylene 2-0, the superficial SMAS is pulled up and fixed to the
      periosteum of the temporal bone. Nineteen patients were so operated on, 14 women
      and 5 men, whose ages varied from 51 to 67 years. Pre- and postoperative
      photographs were taken. The degree of satisfaction was measured from 1 to 3 (1
      being the least satisfactory). Informed consent was signed by all of the
      patients. RESULTS: Satisfactory results were obtained in all cases. Patients
      enjoyed the ease of the procedure. CONCLUSION: This is a simple, quick, and
      noncomplicated way to perform a face-lift. It can be combined with other
      modalities of facial rejuvenation.

PMID- 15871323
TI  - Transcutaneous face-lift.

PMID- 15871324
TI  - Spiral subcutaneous island pedicle advancement flap for repair of alar defects.

PMID- 15871325
TI  - Confidence intervals in procedural dermatology: an intuitive approach to
      interpreting data.
AB  - BACKGROUND: Significant differences observed in therapeutic trials in procedural
      dermatology are typically denoted by p values of less than .05. Alternatively,
      significance can be conveyed by use of confidence intervals. OBJECTIVES: The
      purpose of this article is to clarify how confidence intervals convey the same
      information about outcomes as p values, albeit in a slightly different manner.
      METHODS: (1) Selective review of textbooks and other relevant literature and (2)
      presentation of a brief tutorial describing confidence interval determination for
      therapeutic clinical trials comparing differences between means of two groups.
      RESULTS: Routine use of confidence intervals is an intuitively satisfying means
      for conveying the statistical significance of results and can be used in
      combination with p values for understanding these results. Specifically,
      confidence intervals are a useful tool for indicating the size, spread, and
      direction of the observed differences. Unfortunately, dermatologic surgery trials
      tend to have low sample sizes, which frequently result in outcomes below the
      threshold of statistical significance (p > .05, or confidence intervals including
      1.00). In the absence of statistical significance, neither p values nor
      confidence intervals yield definitive results. CONCLUSION: Confidence intervals
      can complement p values as a means for explaining statistical significant
      differences. When differences are not statistically significant but are
      clinically significant and approach statistical significance, neither p values
      nor confidence intervals can definitively establish whether the observed trends
      are indicative of an underlying difference. In these cases, common in procedural
      dermatology, larger, better designed, randomized prospective trials are needed.

PMID- 15871326
TI  - Multiple atypical fibroxanthomas in a cardiac transplant recipient.
AB  - BACKGROUND: Solid organ transplant recipients have an increased incidence of
      multiple cutaneous neoplasms. OBJECTIVE: We hope to draw attention to the
      potential risk for organ transplant recipients to develop atypical
      fibroxanthomas. METHODS: A review of the patient's medical record was performed
      and summarized as a case report. RESULTS: We present the case of a cardiac
      transplant recipient who developed three atypical fibroxanthomas. This is the
      first reported case of multiple atypical fibroxanthomas in an organ transplant
      recipient. CONCLUSION: Atypical fibroxanthomas are uncommon cutaneous
      malignancies for which transplant recipients may be at increased risk.

PMID- 15871327
TI  - Unusual clinical presentation of regression in a congenital melanocytic nevus.
AB  - BACKGROUND: Regression of congenital melanocytic nevi is usually accompanied by
      the halo phenomenon and is considered a rare event. OBJECTIVE: A 15-year-old
      woman presented for the evaluation of multiple halo nevi. She had on her trunk a
      figure-of-eight pigmentary lesion, which had been developed after the coalescence
      of two distinct congenital melanocytic nevi. Close to the indentation between the
      two portions of the lesion, there was an achromic rounded area, extending from
      the perinevic skin to the nevus, causing its partial regression. METHODS AND
      MATERIALS: Dermoscopic examination disclosed a globular and homogeneous pattern,
      which was irregularly present at the edge of the achromic area. The
      histopathologic diagnosis was compound congenital melanocytic nevus with an
      eccentric area of regression. CONCLUSIONS: In our case, the presence of a
      regression area in the surrounding skin and the association with multiple halo
      nevi suggest a similarity with halo phenomenon, despite the atypical "halo,"
      which was discontinuous and eccentric.

PMID- 15871328
TI  - Artificial skin as a valuable adjunct to surgical treatment of a large squamous
      cell carcinoma in a patient with epidermolysis bullosa.
AB  - BACKGROUND: Among tissue-engineered skins, two bilayered cellular constructs and
      one cryopreserved dermal substitute have been approved for the treatment of
      epidermolysis bullosa. Nevertheless, the application of artificial skin
      technology to surgical treatment of squamous cell carcinomas in a patient with
      epidermolysis bullosa has never been reported. OBJECTIVE: To reconstruct the
      large defect remaining after squamous cell carcinoma excision in a patient with
      dominantly inherited dystrophic epidermolysis bullosa. METHODS: To apply a 10 x
      15 cm Integra sheet (Integral Life-sciences Corporation, Plainsboro, NJ, USA) (an
      acellular collagen matrix coated with a thin polysiloxane elastomer) to the
      excised area and 3 weeks later to cover the Integra sheet with an ultrathin
      meshed skin graft. RESULTS: The graft take was complete, and the donor site
      totally regenerated, except for three small bullae at 7 weeks postoperatively.
      CONCLUSION: Integra offers the advantage of filling huge defects with its dermal
      layer of collagen fibers and provides an optimal graft bed. This first step makes
      it possible to use very thin grafts 3 weeks later.

PMID- 15871329
TI  - Human papillomavirus-associated dysplastic condyloma of the tongue treated with
      Mohs micrographic surgery.
AB  - BACKGROUND: Human papillomavirus (HPV) has been causally associated with benign
      and malignant tumors of the oral mucosa. It is found in the majority of both oral
      condylomas and oral squamous cell carcinomas. Treatment for these lesions
      consists of destructive or traditional surgical excision, respectively.
      OBJECTIVE: Mohs micrographic surgery provides excellent margin control and the
      highest cure rate for cutaneous malignancies, especially squamous cell carcinoma.
      Therefore, it represents an excellent alternative for the treatment of HPV
      associated malignant and premalignant lesions of the oral mucosa, where the high
      rate of metastatic potential is compounded by anatomic complexity and the limited
      amount of normal tissue that may safely be sacrificed with wide excisions.
      RESULTS: A 38-year-old white man presented with a dysplastic condyloma of the
      lateral tongue. High-risk HPV-16 deoxyribonucleic acid (DNA) was detected by
      fluorescent in situ hybridization. Surgical resection of the dysplastic condyloma
      of the tongue by Mohs micrographic surgery resulted in complete lesion removal,
      with no evidence of clinical recurrence 8 months after surgery. CONCLUSIONS: Mohs
      micrographic surgery should be considered as a treatment option for cancerous or
      precancerous lesions of the oral mucosa, especially when the latter are
      associated with high-risk HPV.

PMID- 15871330
TI  - A common tumor, an uncommon location: basal cell carcinoma of the nipple and
      areola in a 49-year-old woman.
AB  - BACKGROUND: Basal cell carcinoma (BCC) occurring on sun-protected regions is an
      uncommon phenomenon. BCC of the nipple is an exceedingly rare event. METHOD: We
      review the literature on BCC of the female nipple and herein describe the eighth
      reported case in the English literature. Our patient was treated with Mohs
      micrographic surgery and sentinel lymph node biopsy. CONCLUSION: BCC of the
      nipple are extremely rare tumors with unclear etiology. They can be aggressive
      and are capable of causing significant morbidity and mortality if they are
      neglected or improperly treated. With continued reporting of the diagnosis,
      treatment, and follow-up of these patients, we may gain an understanding of the
      pathogenesis, as well as the best method of control for these unusual tumors.

PMID- 15871331
TI  - The Kerf-Cut dressing: application of a woodworking technique for efficient
      postsurgical wound care.
AB  - BACKGROUND: Simple surgical excision is one of the most common treatment methods
      in the dermatologist's armamentarium. We describe a precise postsurgical dressing
      technique that can be used for wound care of those patients whose treatment
      involves removal of lesions via cutaneous surgery. OBJECTIVE: To devise a novel,
      precise, and effective dressing technique for postsurgical wound care. MATERIALS
      AND METHODS: We describe the technique using common in-office instruments.
      RESULTS AND CONCLUSION: Wound dressings for lesions located on curved areas such
      as the ears, nose, cheeks, and chin often exhibit less than adequate adherence
      and stability. The kerf-cut dressing technique optimizes pliability of dressing
      tape, and this maximizes efficient and stable application of postsurgical wound
      dressings to curved areas of the body.

PMID- 15871332
TI  - Successful treatment of granulomatous reactions secondary to injection of
      esthetic implants.
AB  - BACKGROUND: In recent years, various injectable materials have come into use to
      improve esthetic appearance. OBJECTIVE: We describe the clinical and
      histopathologic aspects of two patients who received intradermal injections of an
      unknown dermal filler and the different diagnostic tools used to identify the
      unknown injected material (reflexion electron microscopy, electron dispersing x
      ray) and discuss the possibility of a metastatic granulomatous reaction in one
      patient. We also describe two treatments for this complication and evaluate the
      legal considerations of the use of materials that have been adulterated and/or
      whose composition is unknown to the patient. METHODS: We present two patients who
      developed a granulomatous foreign-body reaction after the subcutaneous injection
      of an esthetic implant. We treated patient 1 with isotretinoin and 2 months later
      with doxycycline. We administered isotretinoin to patient 2. RESULTS: We observed
      a partial improvement in patient 1 after isotretinoin treatment and a remarkable
      improvement after administration of doxycycline. In patient 2, we observed an
      excellent response to isotretinoin. CONCLUSION: Isotretinoin and doxycycline,
      when administered separately, seem to offer effective treatment for reactions
      resulting from silicone implants. However, further studies that include a larger
      number of patients and those with reactions secondary to other fillers are
      clearly needed before the effectiveness of this treatment can be confirmed.

PMID- 15871333
TI  - Re: Botulinum toxin for the treatment of facial flushing.

PMID- 15871334
TI  - Re: Postoperative dysesthesia.

PMID- 15871335
TI  - Re: Questionable utility of Melan-A/Mart-1 immunoperoxidase staining while doing
      Mohs surgery for melanoma.

PMID- 15871336
TI  - [Complementary therapies].

PMID- 15871337
TI  - [What is homeopathy?].
AB  - Homeopathy is a curative method whose practice began approximately 200 years ago
      in Germany. Samuel Hahnemann discovered it and spread its practice rapidly
      through Europe and the rest of the world. Homeopathy is different in almost all
      aspects from what may be called "official" medicine, known as allopathy by
      homeopathic practitioners. The basic principle used in homeopathy consists in
      applying what is called similia smilibus curantur likes cure likes, or a
      "similarity law"; that is, all substance are capable of producing in a healthy
      human a series of ills or symptoms. This same substance used in homeopathic
      doses, or "infinitesimal doses" in homeopathic parlance, has the capability to
      cure.

PMID- 15871338
TI  - [Biographic synopsis on Samuel Hahnemann].

PMID- 15871339
TI  - [Phyto-therapy: a choice based on science and tradition].
AB  - Even though plants have been used as therapeutic remedies since men have
      inhabited the Earth, only with advances in pharmaceutical science and the
      development of analytical methods have professionals been able to guarantee the
      necessary control procedures, thereby overcoming many of the inconveniences
      incurred by the traditional use of plants and improving their efficiency. Today,
      phyto-therapy is based on research and experience. The contents of this article
      deal with the quality, efficiency and security of phyto-therapeutic preparations.

PMID- 15871340
TI  - [Medicinal plants useful in the cure of circulatory problems in legs].
AB  - Once the fundamentals of phyto-therapy in its western use are understood, this
      article presents concrete a application of medicinal plants: circulatory problems
      in legs, a problem which affects a growing sector of the population. According to
      epidemiological studies, close to 80% of adults suffer problems such as tired
      legs, swellings, edemas, cramps, or varicose veins during their lifetimes; these
      appear due to an insufficiency when veins can not conveniently transport blood to
      the heart.

PMID- 15871341
TI  - [Sofrology].
AB  - In this article, the authors shall place emphasis on stress among nursing
      professionals and on its psycho-physical consequences. The authors will describe
      the different focuses which are currently recommended to prevent and treat stress
      and they will explain how the sofrology techniques are a good alternative in the
      treatment of stress from the physical, cognitive, emotional and behavioral
      perspectives. The authors conclude by proposing the sofrologic method as a
      discipline which may be practiced by both nursing professional and their
      patients. In both groups, the effectiveness of this method in the prevention and
      treatment of stress has been demonstrated.

PMID- 15871342
TI  - [Reflexology].
AB  - Reflex therapy massage is defined as the study of a concrete massage which
      carried out on determined zones of the body, manifests some effects, which can be
      calming, analgesic, relaxing...on the different organs or body parts in the area
      massaged.

PMID- 15871343
TI  - [Ortho-molecular nutrition].
AB  - Ortho-molecular nutrition contemplates the deficiency of certain nutrients, not
      their deprivation, as the generator of short-term and long-term pathologies. By
      means of supplying these nutrients, an organism recovers. This method consists in
      building up an organism's functions by following the guides and indications
      provided by the organism itself.

PMID- 15871344
TI  - [Music therapy].
AB  - Music therapy is a discipline which often is included in the group of natural,
      complementary and non-pharmaceutical therapies. In this therapy, the importance
      of teamwork and interdisciplinary communication between the musical therapist and
      the other professionals deserve to be highlighted.

PMID- 15871345
TI  - [Preventive vaccinations in childhood (and III)].

PMID- 15871346
TI  - Public private partnership for elimination of leprosy.

PMID- 15871347
TI  - Eye diseases--priority areas to look for.

PMID- 15871348
TI  - Current epidemiology of leprosy.
AB  - Every year around 4,00,000 new cases of leprosy occur in India and India
      contributes about 80% of the global leprosy case load. The prevalence of leprosy
      (case load per 1,00,000 population) has come down from 52 per 10,000 in 1981 to
      2.4 per 10,000 in July 2004. There is no primary prevention for leprosy.
      Multidrug therapy is the only intervention available against the disease. As of
      July 2004 there were about 2,40,000 leprosy cases on record in India. There are
      thirteen states and union territories in India which have already eliminated
      leprosy. About 70% of the cases detected in India are paucibacillary which are
      less or non-infectious. Ever since the start of National Leprosy Eradication
      Programme in 1983, the number of new cases detected every year has not shown
      significant change. Leprosy cases are treated for 6 months or 12 months depending
      on whether they are PB or MB. The treatment completion rates are now found to be
      85% for MB and 90% for PB. Phased introduction of MDT services has contributed to
      a large extent the static level of new case detection. Without complete coverage
      of MDT, it is difficult to achieve stable level of new case detection. Diagnostic
      efficiency of the staff is very important external factor influencing case
      detection rate. The most important factor that could have significant impact or
      prevalence is the coverage of the entire population with adequate MDT service.

PMID- 15871349
TI  - National Leprosy Eradication Programme and progress towards elimination of
      leprosy in India.
AB  - The World Health Assembly in May 1991 made the declaration to eliminate leprosy
      at global level by the year 2000. Complete coverage of all the districts with MDT
      was possible in the year 1996. Very good results were obtained and the case lead
      came down to 0.51 million by December 2000. A new goal has been set to reach
      leprosy elimination at national level in India by December 2005. The challenges
      to eliminate leprosy and to bring prevalence rate 0.9/10,000 by December 2005 are
      to be taken at epidemiological, operational and at administrative levels.

PMID- 15871350
TI  - Clinical manifestations, diagnosis and classification of leprosy.
AB  - Mycobacterium leprae, the causative organism of leprosy is slow-growing and the
      reason is its long incubation period of 2-4 years. Males are predominantly
      affected and deformity is produced in less than 2% of people affected with the
      disease. The disease manifests in the skin as macules, papules, nodules, plaques
      or infiltration. Hypopigmented or erythematous skin patches with definite sensory
      deficit is one of the clinical cardinal signs by which one can make a definite
      diagnosis. Demonstration of bacilli in the slit skin smear is the bacteriological
      cardinal sign used to make definite diagnosis of leprosy. Involvement of common
      cutaneous nerves with thickening and/or tenderness with its dysfunction is the
      second clinical cardinal sign used to diagnose leprosy. Diagnosis can be made by
      eliciting definite sensory deficit in the skin lesions (other than nodules and
      infiltration). In the absence of two clinical cardinal signs and when there is a
      strong suspicion of leprosy, slit skin smear should be taken from both ear lobes
      and one of the lesions for demonstration of acid-test bacilli. Clinical
      classification is based on characteristics like number of lesions, their margin,
      sensory deficit, satellite lesions, symmetry of lesions, central healing and
      scaling. Up to 5 lesions are grouped under paucibacillary and six and more are
      grouped under multibacillary leprosy.

PMID- 15871351
TI  - Prevention of disability in leprosy.
AB  - Leprosy is curable now-a-days if initiatives are taken for prevention of
      disability along with complete and regular chemotherapy. Common disabilities
      encountered in leprosy are: Claw hand, foot drop, lagophthalmos, plantar ulcers
      and depressed bridge of nose. Objectives of prevention of disabilities are
      preservation of nerve function, preservation of vision, to regain functional
      ability and self-esteem. Measures to prevent disabilities include early diagnosis
      and treatment with effective chemotherapy, to train leprosy cases to perform self
      care practices, providing them with protective aids and referring the cases for
      surgery if indicated. Lepra reactions are episodes of sudden increase in the
      activity of the disease. Lepra reactions are treated by bed rest, analgesics rest
      to affected nerve by splints and a suggested course of prednisolone. Besides,
      leprosy-affected persons should be encouraged for self-care practices.
      Counselling and holding care and concern camps (POD camps) are very much
      integrated wtih the prevention of disabilities.

PMID- 15871352
TI  - Counselling of leprosy affected persons and the community.
AB  - "Counselling is a helping process where one person explicitly and purposefully
      gives his/her time, attention and skills to assist a client to explore their
      situation, identity and act upon solutions within the limitations of their given
      environment". The GATHER (greet, ask, tell, help, explain, return visit)
      technique can be useful in successful counselling. Counselling services have been
      proven successful in reducing stigma. While the scope for counselling is quite
      enormous, it will vary according to the specific need. The few common points
      which have been detailed in the text must be followed by all while providing
      counselling in different situations. The points as specified are: (1) Counselling
      of new patients. (2) Counselling of patients under treatment for few months. (3)
      Counselling of patients on completion of treatment. (4) Counselling of family
      members. (5) Counselling of community members. The points mentioned are about
      issues on which counselling should be centred.

PMID- 15871353
TI  - Reactions and their management.
AB  - The uneventful response to chemotherapy in leprosy is marked by clinically
      disturbing episodes encountered in 20-30% of patients and these phenomena are
      called "reactions". Generally they are classified as reversal reaction (type-1)
      and erythema nodosum leprosum (type-2). The cutaneous menifestations are: (1)
      Type-2 reactions in LL, BL types constituting erythema nodosum leprosum, erythema
      multiforme, erythema necroticans, subcutaneous nodules, lepromatous exacerbation.
      (2) Type-1 reactions in borderline and tuberculoid leprosy. The other
      manifestations include: Acute neuritis, lymphadenitis, arthritis, oedema of the
      hands and feet, ocular lesions, etc. Sequelae of reactions are: Paralytic
      deformities, non-paralytic deformities, extensive scarring and renal damage. A
      simple guideline to identify the risk-prone cases has been narrated. Prednisolone
      in standard dosage schedule as recommended by WHO is now being widely used in
      control programmes.

PMID- 15871354
TI  - Chemotherapy of leprosy.
AB  - The WHO MDT regimens have proved highly successful in preventing relapse of
      leprosy cases. It has indirectly lad to marked reduction in prevalence of
      disabilities. For PB leprosy, rifampicin 600 mg monthly and 100 mg dapsone daily
      for a total of 6 months therapy is required. For MB leprosy clofazimine 300 mg
      once monthly, supervised and 50 mg daily self administered is added. For single
      skin lesion the current WHO recommendation is 600 mg rifampicin + 400 mg
      ofloxacin + 100 mg minocycline given as a single dose for adults. Dose adjustment
      for children and clinical information have been discussed in a nutshell. A number
      of trials are going on, some are yet to be completed which do offer the prospect
      of perhaps simplifying therapy and improving with shorter duration.

PMID- 15871355
TI  - Reconstruction of facial deformities in leprosy patients.
AB  - Almost all the parts of the face may be involved in deformities caused by
      leprosy. Reconstructive surgery can be undertaken after the disease is arrested
      by medical treatment. Reconstruction of nose can be done by augmentation with
      autogenous bone graft, retronasal inlay graft, etc. Loss of eyebrows can be
      reconstructed with hair bearing skin with hair follicles. Sagging face can be
      corrected by nasolabial face-lift with correction of glabellar folds.
      Blepharoplasty is done for correction of some conditions. The temporal muscle
      sling is a dynamic procedure to reconstruct facial nerve palsy.

PMID- 15871356
TI  - Reconstructive surgery in upper limbs in leprosy.
AB  - Of all the deformities in leprosy, 80% require minor surgery and the rest major
      surgery. Upper and lower limbs and face are mainly affected by deformities.
      Either the median or ulnar nerve and rarely the radial nerve are involved in
      isolation or in combination. Tendon transfer is the only option available in
      cases of deformities like simian hand, ulnar claw hand, wrist drop and failure to
      the metacarpals. The only motor function to be restored in median nerve palsy is
      opponensplasty. For radial nerve palsy standard FCU transfer, FDS transfer and
      FCR transfer are the reconstructive methods. For ulnar nerve palsy, an intrinsic
      minus hand function is restored by the motors PL, ECRL, FDS, EIP or EDM extended
      by four tail fascia lata graft onto lateral or ulnar bands of fingers. When ulnar
      nerve is part of much more extensive paralysis, reducing the availability of
      suitable motors, static mathods of conection of claw hand are done.

PMID- 15871357
TI  - Community ophthalmology in the Indian perspective.
AB  - Community ophthalmology is as important as practice of clinical ophthalmology.
      Community ophthalmology deals the part of ophthalmology which is meant for
      identifying common causes of ocular morbidity in different regions, assessing the
      needs of the population, selecting appropriate intervention strategies, planning
      education programmes and analysing the utilisation patterns. Community
      ophthalmology denotes the use of appropriate strategies to reduce the burden of
      eye diseases in the community and the consequences of ocular ill health, while
      striving to ensure the best possible ocular health status for a major proportion
      of the community. Community-based services do not mean that institutional care is
      being downgraded. Institutions will always be central to the success of community
      directed programme. The rational for practising community ophthalmology has been
      pointed in the text portion.

PMID- 15871358
TI  - Genetics and bioinformatics of primary open angle glaucoma: an Indian
      perspective.
AB  - Glaucoma is the second largest blinding disorder, after cataract, affecting about
      67 million people worldwide. In India about 1.5 million people are blind due to
      glaucoma. Primary open angle glaucoma is the major sub-type of glaucoma affecting
      all ages and is genetically complex. Myocilin and optineurin are two different
      genes that have been implicated for primary open angle glaucoma. This review is
      focused on the studies being conducted in India on primary open angle glaucoma to
      identify the molecular defects and new directions undertaken using bioinformatic
      approaches towards a better understanding of the disease.

PMID- 15871359
TI  - Diabetic retinopathy for general practitioners.
AB  - The most significant complication of diabetes mellitus involves the eye and which
      develops 85% of all diabetics eventually to retinopathy. Diabetic retinopathy is
      the commonest cause of blindness between 4th and 7th decades. It is essentially a
      microangiopathy with two distinct stages during its evolution, the preclinical
      and clinical stages. Diabetic maculopathy is the commonest cause of visual loss
      in diabetics. Progression of the diseases can be retarded by early diagnosis and
      using appropriate measures. Well known risk factors are diabetes age, metabolic
      control of hypertension, associated renal disease and pregnancy. The management
      plan of the secondary level is early diagnosis and laser photocoagulation or
      surgical intervention. Vitreoretinal surgery is certainly of benefit in patients
      with advanced diabetic eye disease. The PROMPT factors can be applied to decrease
      diabetes mellitus related blindness.

PMID- 15871360
TI  - The efficacy of topical administration of brimonidine to reduce ischaemia in the
      very early stage of diabetic retinopathy in good controlled type-2 diabetes
      mellitus.
AB  - It is now proved that diabetic micro-angiopathy is caused by ischaemia at the
      capillary bed of retina due to reduced capillary blood flow in long standing type
      2 diabetes mellitus. Deranged metabolic process due to chronic hypoxia at the
      tissue level produces visual and vascular dysfunction. Brimonidine tartrate, an
      alpha-2 agonist which is commonly used in glaucoma to protect retinal ganglion
      cells from pressure related ischaemia induced cell apoptosis, is administered in
      very early stage of non-proliferative diabetic retinopathy to reduce ischaemia at
      the capillary bed of retina. Improved visual acuity and decreased micro-aneurysm
      formation, which indicate elimination of ischaemic stimulus at the tissue level,
      are seen in long standing type-2 diabetes mellitus.

PMID- 15871361
TI  - Amniotic membrane transplantation in ocular surface disorders.
AB  - The term ocular surface disorders indicate a close relationship between the
      conjunctival and corneal epithelium in many corneal and external diseases. The
      human amniotic membrane has a thick basement membrane and an avascular stromal
      matrix and its first ophthalmic use was reported by deRoth for conjunctival
      surface reconstruction. It was subsequently used for different ophthalmic
      reasons. Amniotic membrane transplantation can be used in a number of conditions
      eg, as a graft to replace damaged ocular surface stromal matrix or as a patch to
      prevent unwanted inflammatory insults from gaining access to the damaged ocular
      surface. Amniotic membrane can be utilised in persistent of recurrent corneal
      epithelial and stromal defects; in cases of corneal perforation due to ulcer or
      melting; after conjunctival excision for acquired melanosis, neoplasia, etc; in
      cases of pemphigoid, Stevens-Johnson syndrome, chemical bums; in cases of
      symblepharon, in dry eyes or in large leaking filtering blebs.

PMID- 15871362
TI  - Malignant melanoma of conjunctiva--a case report.
AB  - A 65-year-old male patient presented with a rapidly increasing mass in his left
      eye. It did not show any intra-ocular extension as examined by slit lamp,
      gonioscopy, indirect ophthalmoscopy and ultrasonography, nor there was any sign
      of systemic metastasis. The mass was excised completely. Buccal mucous membrane
      grafting was done to cover up the lower forniceal area and conjunctival autograft
      taken from right eye and placed over upper fornix and bulbar area. Postoperative
      radiotherapy was suggested. Histopathological examination of the mass revealed
      the diagnosis of malignant melanoma of conjunctiva.

PMID- 15871363
TI  - Traumatic pseudophacocele.
AB  - A 70-year-old man presented with blunt trauma to his pseudophacic eye, resulting
      in subconjunctival dislocation of the posterior chamber intra-ocular lens. This
      rare incidence of traumatic pseudophacocele, occurring 5 years after cataract
      surgery and how its management salvaged useful vision is reported here.

PMID- 15871364
TI  - Ocular rhinosporidiosis.
AB  - Rhinosporidium seeberi, the causative organism causing rhinosporidiosis, also
      affects extranasal sites. A 1 5-year-old male presented with a conjunctival
      fleshy swelling near the inner canthus of the left eye. His visual acuity was
      within normal range. Conjunctival papilloma was the provisional diagnosis for
      which he was operated on. Histopathology proved to be a case of ocular
      rhinosporidiosis. Six months follow-up of the case showed no recurrence.

PMID- 15871365
TI  - Randomised, double-blind, comparative study to evaluate the efficacy and safety
      of ganaton (itopride hydrochloride) and mosapride citrate in the management of
      functional dyspepsia.
AB  - Prokinetic agents like itopride hydrochloride and mosapride citrate are commonly
      used in the management of functional dyspepsia. However, in a recently conducted
      international, multicentric study, efficacy of 3 different regimens of mosapride
      was shown to be comparable to placebo. The objective of this phase 4 randomised,
      double blind, prospective study was to compare the efficacy and safety of ganaton
      (itopride hydrochloride) and mosapride citrate in the management of functional
      dyspepsia among patients attending the gastroenterology outpatient department of
      a tertiary care hospital. Ganaton 50 mg or mosapride citrate 5 mg three times
      daily before meals for a period of 2 weeks was administered orally. Thirty
      functional dyspepsia patients in each group (total = 60) were randomised to
      receive itopride hydrochloride or mosapride citrate treatment for 2 weeks. In
      itopride versus mosapride groups, global efficacy as judged by patients was
      excellent in 17 versus 9 (p < 0.05) and poor in 0 versus 3 (p < 0.05). In
      itopride versus mosapride group global efficacy as judged by physician was
      excellent in 24 (80%) versus 15 (50%) and poor in 0 (0%) versus 3 (10%) patients
      respectively. The global efficacy was rated as excellent to good in significantly
      (p < 0.05) more number of patients in itopride (93.3%) group as compared to
      mosapride (63.33 %) group. None of the patients reported any adverse events with
      itopride treatment. In the mosapride group 5 patients (16.7%) reported adverse
      events. Two patients (6.7%) were withdrawn from mosapride treatment due to
      adverse events. The physician rated global tolerability ofitopride versus
      mosapride treatment as excellent in 23 (76.7%) versus 8 (26.7%) (p < 0.05) and
      poor in 0 (0%) versus 6 (20%) patients respectively. It may be concluded that
      ganaton (itopride hydrochloride) is superior in efficacy and safety over
      mosapride citrate in the management of functional dyspepsia.

PMID- 15871366
TI  - Is it time for new abortion limits?

PMID- 15871368
TI  - Has the fun gone out of nursing?

PMID- 15871369
TI  - How I coped with a major rail crash. Interview by David Crouch.

PMID- 15871370
TI  - Increased role for nurses in provision of skin cancer care.
AB  - Skin cancers are the most common group of cancers affecting the U.K. population
      and their incidence is rising steadily. Draft guidance from NICE outlines
      initiatives that are needed to tackle the problem, including new developments in
      the provision of nursing care.

PMID- 15871371
TI  - How to diagnose diabetes.
AB  - Rapid, unequivocal diagnosis of diabetes is essential to avoid the onset of
      complications in both type 1 and type 2 diabetes. The signs and symptoms of
      diabetes can vary with individuals and therefore are not reliable for diagnosis.
      The World Health Organization has provided guidance concerning the diagnosis of
      diabetes and impaired glucose regulation. This makes use of venous blood glucose
      results, with or without symptoms, to enable a prompt and sound diagnosis.

PMID- 15871372
TI  - Spina bifida.

PMID- 15871373
TI  - Implementing nurse-led discharge from day surgery.
AB  - The demands now placed upon the NHS to reduce waiting lists and cut costs mean
      that day surgery is being seen not only as a way forward for elective surgery,
      but also as a key factor for assisting in the bed management of acute services.
      This article focuses on the practical steps that health and social care
      professionals can take to improve discharge processes in their care settings.

PMID- 15871374
TI  - Loperamide.

PMID- 15871375
TI  - Using the ventrogluteal site for intramuscular injections.
AB  - Traditionally, the dorsogluteal site has been the site preferred by nurses for
      the administration of medication via intramuscular injection. However, there is
      evidence to support the use of the ventrogluteal site. It was recently advocated
      as the site of choice in a respected nursing manual. This article discusses the
      use of the ventrogluteal site, the intramuscular injection technique, and issues
      associated with teaching it.

PMID- 15871376
TI  - Ensuring more holistic care for patients with dyspnoea.

PMID- 15871377
TI  - Sharing information on the intranet.

PMID- 15871378
TI  - Using negative pressure therapy for healing of a sternal wound.
AB  - Lisa Clubley and Lorraine Harper examine the treatment provided to a patient who
      had cardiac surgery and developed complications that resulted in the development
      of an extensive open sternal wound. The consultant surgeon responsible for the
      care made a decision to use negative pressure therapy (vacuum-assisted closure)
      despite such therapy for a wound of this nature being contraindicated in the
      manufacturer's clinical guidelines

PMID- 15871379
TI  - Managing leg ulceration in patients with sickle cell disorder.
AB  - Leg ulceration is a complication associated with sickle cell disorders. Caroline
      Dowsett outlines why this problem occurs and describes the management of a
      patient with sickle cell disorder who presented with an infected leg ulcer. She
      concludes that there is a need for more research into the management of these
      complex wounds.

PMID- 15871380
TI  - Understanding wound dressings: alginates.
AB  - A variety of wound dressing groups is currently available on prescription. In a
      series of six articles, Jacqui Fletcher looks at the different groups of
      dressings, their composition, and indications for use. This first article looks
      at alginates. The second article in the series discusses foam dressings, and will
      appear in the Wound Care Supplement of 7 June.

PMID- 15871381
TI  - Using an adhesive retention tape on split skin graft donor areas.
AB  - Donor split skin graft areas are often painful, a problem that can be exacerbated
      when dressings that have been applied slip, particularly when they are on the
      patient's thigh. Helen McPhee carried out a small trial to assess whether Mefix,
      an adhesive retention tape, could help to reduce these problems

PMID- 15871382
TI  - Dealing with difficult difficult people and situations.

PMID- 15871383
TI  - Where split seconds can save lives.

PMID- 15871385
TI  - [Not working, still veterinary medicine].

PMID- 15871384
TI  - [Autochthonous babesiosis in dogs in The Netherlands associated with local
      Dermacentor reticulatus ticks].
AB  - In the spring and autumn of 2004, 20 respectively 3 cases of autochthonous canine
      babesiosis were diagnosed in the Netherlands, four of which ended fatally. Adult
      Dermacentor reticulatus ticks were found on four dogs. Case descriptions and
      diagnostics of this B. canis outbreak are discussed in more detail.

PMID- 15871386
TI  - [Professor of Animals and Rights, Annelies Freriks: "It is important to know the
      boundaries you work in as a veterinarian"].

PMID- 15871387
TI  - [Veterinarian and search-and-rescue dog trainer Ester van Neerbos: "Finding the
      diseased is very important to the surviving family members"].

PMID- 15871388
TI  - [Employment conditions in the veterinary profession: take the cow by the horns!].

PMID- 15871389
TI  - [Perforation of the cecum in the horse, coincidental or not?].

PMID- 15871390
TI  - [Symposium "Emerging Zoonoses." Dutch Association for Veterinary Epidemiology and
      Economy (VEEC)].

PMID- 15871391
TI  - [Organization Doctor-U, radiotherapy center for domestic animals with cancer].

PMID- 15871392
TI  - [Commission for Promoting Veterinary Products].

PMID- 15871393
TI  - [Many complaints about NHZ domestic animal insurance].

PMID- 15871394
TI  - [Validity of the rabies vaccine when traveling with domestic animals].

PMID- 15871395
TI  - [Diclofenamide].

PMID- 15871396
TI  - [Food hypersensitivity and fur discoloration].

PMID- 15871397
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, et cetera. Jeannette Voet surrounded by other students].

PMID- 15871398
TI  - [Recognizing and treating stress].

PMID- 15871399
TI  - [Lowering stress levels in the workplace].

PMID- 15871400
TI  - ["Development of awareness of the nursing diagnosis process"].

PMID- 15871401
TI  - [The entire process fails without nursing knowledge].

PMID- 15871402
TI  - [Restoring meaning to life].

PMID- 15871403
TI  - [Nursing is a caring and aware connection].

PMID- 15871404
TI  - [Brave New World].

PMID- 15871405
TI  - ["I am taking for myself a piece of foolish freedom"].

PMID- 15871406
TI  - [The agony of choice].

PMID- 15871407
TI  - [Aware of the normal].

PMID- 15871408
TI  - [The language of the "silent aged"].

PMID- 15871409
TI  - [Less distinction in the management of mental retardation].

PMID- 15871410
TI  - [Lives changed by AIDS].

PMID- 15871411
TI  - [And what are the problems of maintaining home care?].

PMID- 15871412
TI  - [Careers for men, careers for women: really?].

PMID- 15871414
TI  - [The distance between relations].

PMID- 15871413
TI  - [Costs and revenues should agree].

PMID- 15871415
TI  - [Optimal assistance thanks to intercultural competence].

PMID- 15871416
TI  - Stem cells in medical techonology.
AB  - Major ethical and scientific debates surround the potential of stem cells to
      radically alter therapies in health care. This article provides some basic
      background on the origins and functions of stem cells.

PMID- 15871417
TI  - Smart implant materials.
AB  - The combination of stimuli-sensitive implant materials and minimally invasive
      surgery techniques is expected to give rise to numerous applications.
      Biodegradable thermoplastic elastomers are presented here as an example of a
      group of biodegradable implant materials with shape-memory properties. Their
      capabilities and use in a smart suture are described.

PMID- 15871418
TI  - Effects of x-ray irradiation on material properties.
AB  - With a new commercial sterilisation technique about to enter the market, this
      article details a study that compared the effects of existing electron-beam
      irradiation with X-ray irradiation on different types of plastics commonly used
      in the manufacture of medical devices. The results are evaluated here.

PMID- 15871419
TI  - Working on the design of new medical implants.
AB  - This report on work currently underway on innovative implants describes the
      progress being made with wireless communication and the lessons learned after one
      year of development of an artificial sphincter and an intracranial pressure
      sensor.

PMID- 15871420
TI  - How to develop reliable sofware.
AB  - A well-defined method for the design and development of software leads to more
      reliable software and products that get to market quicker. This article describes
      how to achieve this and examines good practice, modelling and embedded systems.

PMID- 15871421
TI  - U.S. medical device reporting: who is responsible?
AB  - When various companies are involved in the manufacture and export of medical
      devices to the United States (U.S.), it is not always easy to understand the
      reporting responsibilities under the U.S. Medical Device Reporting regulation. A
      new rule has been published to help companies better understand the requirements.
      This article discusses the new rule, ways to determine responsibilities and
      suggestions for compliance.

PMID- 15871422
TI  - Open innovation or open house: how to protect your most valuable assets.
AB  - Many businesses have difficulty in effectively managing their intellectual
      property. This article offers advice, particularly for smaller companies, on how
      to protect their ideas and thereby be able to benefit from an open system of
      product innovation.

PMID- 15871423
TI  - Creating a fair and competitive market place.
AB  - The prevailing imbalance in the buyer-seller relationship is threatening access
      of innovative medical technologies to patients. Proposed steps to remedy the
      situation are outlined here.

PMID- 15871424
TI  - Ergonomics brings accuracy to quality control.

PMID- 15871425
TI  - Designers, why not use metals?

PMID- 15871426
TI  - Using ceramic in specialist applications.

PMID- 15871427
TI  - Extending the boundaries of identification.

PMID- 15871428
TI  - The importance of executive functions.

PMID- 15871429
TI  - Learning disorders.

PMID- 15871430
TI  - A 15-year-old girl with a fever following an abortion.

PMID- 15871431
TI  - A 22-month-old boy with slow development.

PMID- 15871432
TI  - Management of the child with a learning disorder.
AB  - The label "learning disabilities" is all-embracing; it describes a syndrome, not
      a specific child with specific problems. Parent involvement in and collaboration
      with pediatricians and schools in navigating service systems, accessing
      appropriate services, and case management are particularly relevant for children
      with LD. Comprehensive service delivery in school settings requires the interface
      of other service sectors, such as primary care, mental health,and other community
      agencies that also recognize and address children's problems. To date, marked
      differences exist among the assessment, classification and diagnostic, and
      treatment practices of these service systems, despite the fact that they address
      the same patient population--school-aged youth. Additionally, many of these
      agencies and systems operate in isolation with limited cross-sector communication
      or service collaboration. Parent involvement and advocacy, with assistance from
      pediatricians and knowledgeable school personnel, is necessary to ensure that
      appropriate resources available from these sectors are well coordinated and
      provided for children with an LD to improve their school performance and ongoing
      educational experience.

PMID- 15871433
TI  - Identifying school performance problems in the pediatric office.
AB  - The AAP has underscored the role and responsibility of pediatricians in screening
      their patients for developmental and learning problems and working with parents,
      schools, and other professionals to ensure that students with these problems
      receive appropriate educational and therapeutic interventions. We have proposed a
      model that is time-efficient and can be tailored to the level of interest and
      experience of the pediatrician. At a minimum, the primary care physician should
      elicit any parental concerns about school performance, affirm these, and direct
      the student and parents to appropriate resources in the community for further
      evaluation and intervention as necessary. Pediatricians who wish to understand
      more fully the nature and underpinnings of their patients' learning difficulties
      can formulate a preliminary diagnosis and develop a plan for treatment using a
      structured system of information gathering that can be combined with information
      about the child's medical status and supplemented by brief direct testing in the
      office setting. By following these approaches, primary care pediatricians can
      provide comprehensive care for their patients and their families in their medical
      home and also can derive considerable professional satisfaction.

PMID- 15871434
TI  - Language-based learning disorders.

PMID- 15871435
TI  - Executive functions.
AB  - Executive functions are higher-order cognitive processes that continue to develop
      well into adulthood. They are critically important to behavioral self-control and
      task performance, and deficits can have serious effects on a student's
      functioning in many areas. Primary care pediatricians can play an important role
      by being aware of this evolving field of research, current assessment strategies,
      and by encouraging families, schools, and students to adopt a positive and
      problem-solving approach to improve executive functions.

PMID- 15871436
TI  - Nonverbal neurodevelopmental dysfunctions.
AB  - Although perhaps not as well-studied or well-known as other learning disorders,
      the possible academic and social sequelae of math, writing, motor, or
      visuospatial dysfunction, as well as difficulties with nonverbal processing and
      understanding, are readily identifiable and worthy of identification. While
      pediatricians should not feel compelled to attempt to identify all of the
      variables of these difficulties, an understanding of them will allow
      pediatricians to maintain their role as an advocate for patients and families and
      to feel comfortable communicating with others who are equally dedicated to
      children.

PMID- 15871437
TI  - Early identification of learning disorders helps children succeed.

PMID- 15871438
TI  - Cromolyn sodium: fitting an old friend into current asthma treatment.
AB  - Cromolyn sodium (Intal) has been available in the United States to treat asthma
      for more than 30 years. Its clinical efficacy in patients with mild or moderate
      persistent asthma is well documented, and its extensive clinical record of safety
      remains unique among antiasthma medications. The history of cromolyn sodium
      complements the science behind current understanding of asthma pathophysiology.
      Cromolyn sodium was the first nonsteroid, antiasthma drug that blocked chemical
      mediator release at the cellular level. However, the younger generation of health
      care providers may not be familiar with the medication due to the plethora of
      antiasthma agents that have recently become available. This review reexamines the
      role of cromolyn sodium (now available as an HFA aerosol) in the treatment of
      asthma.

PMID- 15871439
TI  - Time trends in obesity among adults with asthma in the United States: findings
      from three national surveys.
AB  - Obesity may affect the respiratory health of people with asthma. Because the
      temporal trends in the prevalence of obesity among people with asthma have not
      been described in the United States, our objective was to describe these trends.
      Using data from National Health and Nutrition Examination Survey (NHANES) I (1971
      1975), II (1976-1980), and III (1988-1994), the authors examined changes in the
      prevalence of obesity during the period covered by these surveys. The age
      adjusted prevalence of current asthma was 3.5% for NHANES I, 3.1% for NHANES II,
      and 5.2% in NHANES III. Among people with current asthma, age-adjusted mean body
      mass index increased from 26.1 kg/m2 in the NHANES I to 28.0 kg/m2 in NHANES III,
      and the age-adjusted prevalence of obesity increased from 21.3 to 32.8%. Among
      people without asthma, age-adjusted mean body mass index increased from 25.4
      kg/m2 in NHANES I to 26.6 kg/m2 in NHANES III, and the prevalence of obesity
      increased from 14.6 to 22.8%. These results show that people with asthma are far
      more likely to be obese than people who do not have asthma. Because excess weight
      may adversely affect the respiratory health of people with asthma, weight
      management for overweight and obese patients with asthma may be an important
      component in the medical care of these patients.

PMID- 15871440
TI  - Asthma development with obesity exposure: observations from the cohort of the
      National Health and Nutrition Evaluation Survey Epidemiologic Follow-up Study
      (NHEFS).
AB  - Results of cross-sectional studies suggest an association between body mass index
      and asthma. However, it is not clear whether the occurrence of asthma precedes
      increased body mass index or vice versa. From 1971 to 1975, the First National
      Health and Nutrition Examination Survey collected height and weight data and
      information about doctor-diagnosed asthma from 14,407 subjects aged 25-74. In
      1982 through 1985, information was again obtained on doctor-diagnosed asthma with
      a follow-up rate of 84.8%. We took this opportunity to examine the relationship
      between body mass index (BMI) and asthma in this cohort. Subjects with subnormal
      BMI and subjects admitting current or history of doctor-diagnosed asthma were
      excluded from the cohort. Mean follow-up was 10 years (range 6.7-13 years).
      Analyses were adjusted for race and gender. Logistic regression analysis was
      conducted with asthma as the dependent variable and BMI modeled as a categorical
      independent variable (BMI groups). At baseline and at follow-up, increasing BMI
      was associated with increased prevalence of asthma. During the observation
      interval, however, no increased incidence of asthma associated with increasing
      BMI was noted. In comparison with normal BMI, the relative risk (RR) for
      development of doctor-diagnosed asthma in elevated BMI was 1.0 (95% confidence
      interval 0.9-1.2), for markedly elevated BMI was 1.0 (0.8-1.3), and for severely
      elevated BMI was 1.1 (0.8-1.5). Race did not affect this relationship. African
      Americans had an increased risk of asthma, but the risk was unassociated with
      increasing BMI. Gender did not affect this relationship. The disease burden of
      asthma appeared in normal weight and slightly overweight women rather than obese
      and markedly obese women. These results suggest that asthma development may be a
      point on the trajectory of chronic obesity disease or asthma appears with obesity
      as a concurrent disorder.

PMID- 15871441
TI  - Efficacy and safety of formoterol delivered via a new multidose dry powder
      inhaler (Certihaler) in adolescents and adults with persistent asthma.
AB  - Our objective was to compare the efficacy and safety of formoterol (Foradil)
      delivered via a novel multidose dry powder inhaler (Certihaler) with placebo and
      albuterol [pressurized metered-dose inhaler (pMDI)], in patients with persistent
      asthma. After a 2-week run-in phase, 265 patients (13-81 years) previously
      treated with regular/PRN bronchodilators for persistent asthma were randomized to
      12 weeks' double-blind treatment with formoterol 10 microg BID via Certihaler (n
      = 86), albuterol 180 microg QID via pMDI (n = 88) or placebo (n = 91). The
      primary efficacy variable was 12-hour AUC of FEV1 after 12 weeks' treatment.
      Secondary efficacy variables included peak expiratory flow (PEF), rescue
      bronchodilator medication use, asthma-related quality of life (Juniper Mini
      Asthma Quality of Life Questionnaire), and asthma symptom scores. Formoterol via
      the Certihaler had an onset of action within 5 minutes and was associated with a
      clinically relevant and statistically significant increase in 12-hour AUC of FEV1
      after 12 weeks' treatment compared with placebo and albuterol (p < 0.001 and p <
      0.05, respectively). Average PEF was significantly superior for formoterol
      compared with placebo and albuterol (p < 0.001 and p < 0.05, respectively).
      Compared with placebo, rescue albuterol use during the study was significantly
      lower for formoterol (p < 0.01) and was accompanied by a trend toward an
      improvement in asthma-related quality of life (QoL). Asthma symptom scores
      improved to a similar extent for all treatment groups. Treatment with formoterol
      via Certihaler was well tolerated. Formoterol 10 microg BID, delivered via the
      novel Certihaler device, is well tolerated and provides rapid, long-lasting, and
      clinically superior bronchodilation to placebo and albuterol via pMDI in patients
      with persistent asthma.

PMID- 15871442
TI  - Predictors for typical asthma onset from cough variant asthma.
AB  - Cough variant asthma is recognized to be a precursor of asthma or preasthmatic
      state because nearly 30% patients with cough variant asthma develop typical
      asthma within several years. However, predictors for risk of typical asthma onset
      from cough variant asthma are unknown. Forty-one patients with cough variant
      asthma (median age 50 years, 13 men and 28 women), who had undertaken spirometry,
      bronchial reversibility test, methacholine provocation test, measurements of
      peripheral blood eosinophil count, serum total IgE, and specific IgE to common
      allergens, and induced sputum eosinophil count at presentation, were followed up
      with special emphasis on typical asthma onset during 1 year or more (median 4
      years, range 1-12.4). Long-term inhaled corticosteroids (ICS) were taken in 27
      patients. Univariate and multivariate logistic analyses were performed to
      determine the predictors for typical asthma onset. Asthma onset was recognized in
      7 patients. Bronchial hyperresponsiveness, peripheral blood eosinophil count, and
      no use of ICS were significant predictors for the typical asthma onset by
      univariate analysis. However, only bronchial hyperresponsiveness was the
      significant predictor when multivariate analysis was used (adjusted OR 0.028, 95%
      CI 0.001-0.783, p = 0.0355). Bronchial hyperresponsiveness may be the most
      important predictor for risk of typical asthma onset from cough variant asthma.

PMID- 15871443
TI  - Real-life environmental tobacco exposure does not affect exhaled nitric oxide
      levels in asthmatic children.
AB  - Serial measurement of exhaled nitric oxide (eNO) has been shown to be a good
      noninvasive marker of asthma control. Active smoking decreases eNO levels. The
      effect of real-life environmental exposure to tobacco smoke (ETS) on eNO levels
      is not known. Our objective was to study the impact of environmental tobacco
      exposure on eNO levels in asthmatic and non-asthmatic children. Single breath off
      line collection of eNO was performed in asthmatic and non-asthmatic children with
      and without ETS. Urine was collected for cotinine/nicotine analysis. Fifty-seven
      children were enrolled, of which 25 were asthmatic and 32 had smoke exposure. One
      active smoker was excluded from the data analysis. The mean eNO was 11.1 ppb (n =
      31; SD = 18.5) in those passively exposed vs. 11.1 ppb (n = 25; SD = 19.9) among
      the unexposed (not statistically significant). The mean eNO was 6.1 (n = 32; SD =
      4.4) among the non-asthmatics and 17.8 (n = 24; SD = 27.4) among the asthmatics
      (p = 0.02; CI: 1.9-21.6). Real-life environmental tobacco exposure does not
      appear to decrease eNO levels in asthmatic children. Off-line collection of
      exhaled nitric oxide with a Mylar collection device helps differentiate
      asthmatics from non-asthmatics.

PMID- 15871444
TI  - Vaccination with DNA encoding human T-cell epitopes suppresses Der p induced
      allergic responses in mice.
AB  - The apparent complexity of allergen-specific T-cell response in terms of epitope
      usage in humans is a potential barrier to peptide-based immunotherapy for
      allergy. A knowledge of cross-reacting T-cell epitopes of common allergens might
      have an impact on the development of vaccines for immunotherapy. We examined the
      efficiency of vaccinating with plasmid DNA coding only human T-cell epitopes on
      the suppression of allergic reactions in mice. BALB/c mice that received an
      injection of mixed naked DNA plasmids encoding the five classes of human T-cell
      epitopes on Der p 1 and Der p 2 produced a significant reduction in total and Der
      p-specific immunoglobulin E (IgE) synthesis. In Der p specific-IgG2a antibody
      responses, vaccinated mice showed more prominent responses than controls. Higher
      levels of interferon-gamma, a Th1 cytokine associated with the suppression of IgE
      production, were found in the sera of vaccinated mice. Histologic studies showed
      a marked reduction in the infiltration of inflammatory cells in the lung tissues
      of vaccinated mice vs. controls. These results suggest that vaccination with DNA
      encoding human T-cell epitopes effectively inhibits allergic responses in mice
      and might induce cross-regulation on helper T-cell level in vivo.

PMID- 15871445
TI  - Tolerability of selective cyclooxygenase inhibitor, celecoxib, in patients with
      analgesic intolerance.
AB  - Intolerance reactions to acetyl salicylic acid (ASA) and nonsteroidal anti
      inflammatory drugs (NSAIDs) are common and caused by inhibition of COX-1 enzyme.
      Therefore, drugs that selectively inhibit COX-2 enzyme may be safe in these
      subjects. In this study, we evaluated the tolerability of celecoxib, a selective
      COX-2 inhibitor, in patients with analgesic intolerance. The eligible study
      population consisted of patients with a history of urticaria/angioedema, naso
      ocular symptoms, bronchospasm, and/or anaphylactoid reaction induced by ASA
      and/or NSAIDs. A single-blind, placebo-controlled oral challenge test was
      performed in the hospital setting. On 2 separate days, 1/4 and 3/4 divided doses
      of placebo and celecoxib (Celebrex 200 mg, Pfizer, Turkey) were given with 2-hour
      intervals. Seventy-five subjects (mean age: 38.2 +/- 1.4 years; F:M: 55:20) were
      included in the study. Twenty-one subjects had asthma. No reaction was observed
      with placebo or celecoxib provocation. Although celecoxib seems to be a safe
      alternative drug in our study group, considering its serious adverse events
      reported in the literature, the drug should be recommended for patients with
      analgesic intolerance only after being tested by an experienced allergist.

PMID- 15871446
TI  - Soluble CTLA-4 in sera of patients with bronchial asthma.
AB  - Cytotoxic lymphocyte associated antigen-4 (CTLA-4) is a homologue of CD28, which
      plays a critical role in the down-regulation of antigen-activated immune
      response. The aim of the present study was to investigate the concentrations of
      soluble CTLA-4 in sera of patients with bronchial asthma and the correlation
      between soluble CTLA-4 concentrations and some clinical measures of asthma. The
      concentrations of serum soluble CTLA-4 in 31 atopic asthmatics, 20 non-atopic
      asthmatics, and 28 non-atopic normal control volunteers were determined by ELISA
      technique, and the relationship between serum soluble CTLA-4 concentrations in
      asthmatics and airway responsiveness, pulmonary function, blood white cell counts
      and differentials, respectively, were analyzed. Serum soluble CTLA-4
      concentrations in both atopic asthmatics (20.2 +/- 5.4 microg/L) and non-atopic
      asthmatics (19.2 +/- 6.2 microg/L) were all higher than that in normal controls
      (1.8 +/- 0.8 microg/L, p = 0.04 and 0.014, respectively). There was no difference
      in serum soluble CTLA-4 concentrations between atopic and non-atopic asthmatics
      (p = 0.877). The serum soluble CTLA-4 concentrations in the asthmatics
      statistically correlated with forced expiratory volume in one second (r = -0.410,
      p = 0.027), percentage of predicted peak expiratory flow (r = -0.449, p = 0.015),
      and PaCO2 (r = 0.555, p = 0.002), respectively. Our data also showed that the
      concentration of soluble CTLA-4 was significantly related to blood lymphocyte
      numbers. The serum soluble CTLA-4 protein level was significantly elevated in
      patients with asthma. This level correlated with the severity of asthma. Our data
      also showed that the concentration of soluble CTLA-4 was significantly related to
      blood lymphocyte numbers.

PMID- 15871447
TI  - Relationship between vascular endothelial growth factor and angiopoietin-2 in
      asthmatics before and after inhaled beclomethasone therapy.
AB  - Vascular endothelial growth factor (VEGF) and Angiopoietin-2 (Ang-2) play
      complementary roles in the process of vascular remodeling. Therefore, this study
      was designed to examine an interaction between VEGF and Ang-2 in asthmatic
      airways. VEGF, Ang-2, and hepatocyte growth factor (HGF) levels in induced sputum
      obtained from 17 asthmatic patients and 10 normal control subjects were examined.
      Eight weeks of inhaled beclomethasone dipropionate (BDP) therapy (800 microg/day)
      was administered to all asthmatic patients, and sputum induction was repeated.
      VEGF, Ang-2, and HGF levels in induced sputum were significantly higher in
      asthmatic patients than in control subjects. Ang-2 levels were significantly
      correlated with VEGF levels but not with HGF levels. We also found that there was
      a significant correlation between airway vascular permeability index and VEGF
      levels but not HGF levels. In addition, VEGF/Ang-2 ratio in asthmatic patients
      was significantly higher than that in control subjects, and it was significantly
      correlated with airway vascular permeability index. After inhaled BDP therapy,
      VEGF levels were significantly decreased, but Ang-2 levels did not change.
      Therefore, VEGF/Ang-2 ratio after BDP therapy was markedly decreased to the same
      level as in the control subjects. Our findings suggest that interaction between
      VEGF and Ang-2 in asthmatic airways may exist and that high VEGF/Ang-2 ratio may
      be responsible for increased airway microvascular permeability. In addition,
      inhaled glucocorticoids therapy may reduce airway vascular permeability and
      remodeling via VEGF/Ang-2-dependent mechanism.

PMID- 15871448
TI  - The vital few or the trivial many?

PMID- 15871449
TI  - Clinical outcomes for early childhood caries.

PMID- 15871450
TI  - Oral health care for the internationally adopted child: a case report.
AB  - While the health considerations of the internationally adopted child have been
      widely discussed in the medical scientific literature, there has not been
      substantial discourse on the oral health needs of international adoptees. The
      purpose of this case report is to review some of the medical implications
      associated with international adoption and, more importantly, highlight some of
      the potential oral health complications present in this at-risk group of
      children.

PMID- 15871451
TI  - Periodontitis as manifestation of Crohn's disease in primary dentition: a case
      report.
AB  - The purpose of this case report is to detail an initial periodontal manifestation
      of Crohn's disease in a 6-year-old boy. The first clinical diagnosis, localized
      aggressive periodontitis, was based on the microbiological isolation of
      Actinobacillus actinomycetemcomitans from subgingival sites. On examination,
      gingival lesions, together with bleeding on probing, edema, and erythema, were
      observed. Although an increased probing depth was detected, no radiographically
      visible alveolar bone loss was observed. According to these findings,
      periodontitis as a manifestation of a systemic disease was assumed. Furthermore,
      fissural ulcerations of the lips were noted. The patient also reported a swelling
      of the upper lip in the morning. Oral hygiene procedures, scaling, root planning,
      and the application of metronidazole and amoxicillin were not successful.
      Metabolic and several immunological tests, however, showed normal values. Two
      months after the first periodontal signs, the child suffered from severe
      malnutrition, accompanied by diarrhaea and abdominal pain. Active colitis with
      multiple granulomas was detected histopathologically from biopsies. Crohn's
      disease was then diagnosed by the internist. If in doubt, medical examinations in
      every case of childhood periodontitis are recommended to determine whether the
      findings speak for initial symptoms of a systemic disorder (eg, Crohn's disease).

PMID- 15871452
TI  - Hypodontia involving only mandibular permanent canines: report of six cases.
AB  - Agenesis of mandibular permanent canines is uncommon. The occurrence of such an
      anomaly in patients with all other permanent teeth present, except third molars,
      is even more rare. The purpose of this case report was to summarize the
      radiographic findings in 6 Chinese children with hypodontia involving only
      mandibular permanent canines. The etiology of such an anomaly is not known, but
      both genetic and environmental factors may play a role.

PMID- 15871453
TI  - Relationship between needle phobia and dental anxiety.
AB  - PURPOSE: This cross-sectional study aimed to explain the nature of needle phobia
      and its relationship in dental phobic children with evidence on age-related
      differences. METHODS: The study used 2,865 patients (52% boys, 48% girls), 4 to
      11 years old (mean=7.18 years). The patient sample included randomly selected
      patients (N=2,153) and an anxious group of children (N=712). Children were
      divided into 3 age groups (4-6, 7-9, and 10-11 years). The Children Fear Survey
      Schedule--Dental Subscale (CFSS-DS) was used to assess age-related needle phobia
      (CFSS-DS question 3) and dental anxiety. Children were arranged into 3 anxiety
      groups (cutoffs=scores of 25 and 37). Children who scored >37 were considered
      needle-phobic. Statistical analysis was performed using Statistics for Windows
      10. RESULTS: Needle phobia progressively decreases with increasing age (19% of 4-
      to 6-year-old vs 11% of 10- to 11-year-old needle phobics; P< or =05). Stepwise
      regression analysis revealed needle phobia does not primarily seem to be related
      to dental anxiety. Other aspects, like having had someone examine the mouth and
      the dentist drilling, contribute the most to dental anxiety in both low- and high
      anxiety children. Fear of doctors is more specific for high-anxiety children (P <
      or =05). A significant age-related difference regarding needle phobia is found
      between children ages 4 to 6 and 7 to 9 and between children ages 4 to 6 and 10
      to 11 (P < or =001). CONCLUSIONS: Needle phobia is age related, but should be
      considered a separate phenomenon. It is not specific for dental anxiety and is
      related to other painful treatment.

PMID- 15871454
TI  - Triple teeth: case report of an unusual fusion of three teeth.
AB  - An unusual case of fusion between primary central incisors, lateral incisors, and
      a supernumerary tooth is reported. The fusion was at the enamel and cementum
      only, and the tooth was extracted.

PMID- 15871455
TI  - Microleakage of restorative techniques for pulpotomized primary molars.
AB  - PURPOSE: This study's purpose was to assess in vitro microleakage of different
      restorative materials after pulpotomies in primary molars. METHODS: Proximo
      occlusal cavity preparations were prepared in 60 extracted primary molars. The
      selected teeth had at least 3 sound walls and one half to two thirds of root
      length remaining. Carious tissue was removed, pulpotomy was performed, and IRM
      filled the pulp chamber. The teeth were then randomly divided equally into 5
      groups and restored as follows: (1) group 1 with a compomer; (2) group 2 with a
      reinforced glass ionomer material; (3) group 3 with amalgam; (4) group 4 with a
      stainless steel crown (SSC); and (5) group 5 with IRM only (control). After
      thermocycling for 500 cycles, teeth were immersed in dye for 24 hours and
      progressively ground prior to microleakage evaluation. The worst result for each
      section was logged and results were statistically analyzed (Kruskal-Wallis and
      Mann-Whitney). RESULTS: Group 1 showed the highest percentage of no leakage of
      all groups. Leakage from occlusal and cervical margins was markedly shown for all
      specimens of groups 2, 3, and 5. CONCLUSIONS: (1) Bonding agents and resin based
      restorations were able to provide the best total margin protection. (2) SSCs
      cemented with glass ionomer cement were unable to hermetically seal teeth; and
      (3) Tytin, Ketac Molar, and IRM restorations did not appear to be leakage
      resistant materials for pulpotomies of primary molars.

PMID- 15871456
TI  - Clinical evaluation of two different methods of stainless steel esthetic crowns.
AB  - PURPOSE: The purpose of this study was to compare the clinical success of
      stainless steel crowns (SSCs) made esthetic by open facing or veneering on
      posterior primary teeth. METHODS: Thirty-three crowns (18 open-face and 15
      veneered) were placed and followed up for 18 months with semiannual evaluations.
      RESULTS: Crowns made esthetic with the open-face method showed a success of 95%,
      while the veneered crowns showed a success of 80% based on greater than two
      thirds facing retention. Statistical evaluation by 2 proportion test showed no
      significant difference between groups (P>.05). In addition, a statistically
      significant difference was found between upper and lower crowns by Fisher's exact
      test (P<.05). CONCLUSIONS: This study showed that open-face SSCs had a higher but
      not significantly different success rate than veneered SSCs. Upper-arch crowns
      exhibited a higher success rate than those in the lower arch.

PMID- 15871457
TI  - Self-inflicted gingival injury in a pediatric patient: a case report.
AB  - Self-inflicted oral mutilation can result in oral lesions that are difficult for
      a pediatric dentist to diagnose. Sometimes its execution is premeditated, but it
      can also happen accidentally or as the result of an unconscious, deleterious
      habit. The purpose of this case report was to describe: (1) the diagnosis of a
      gingival lesion caused by self-inflicted oral mutilation in a 9-year-old patient;
      and (2) the proposed treatment.

PMID- 15871458
TI  - Female dental practitioners and care of special needs children.
AB  - Increased numbers of female pediatric and general dentists are considered in
      terms of their potential to provide services for children (and adults) with
      special health care needs. Reviewed in this are: (1) practitioner work patterns;
      (2) increasing numbers of children in community residences; (3) the general need
      for dental services; (4) changing educational standards; and (5) practitioner
      willingness to provide care.

PMID- 15871459
TI  - Gene recognition based on nucleotide distribution of ORFs in a hyper-thermophilic
      crenarchaeon, Aeropyrum pernix K1.
AB  - The 2694 ORFs originally annotated as potential genes in the genome of Aeropyrum
      pernix can be categorized into three clusters (A, B, C), according to their
      nucleotide composition at three codon positions. Coding potential was found to be
      responsible for the phenomenon of three clusters in a 9-dimensional space derived
      from the nucleotide composition of ORFs: ORFs assigned to cluster A are coding
      ones, while those assigned to clusters B and C are non-coding ORFs. A
      "codingness" index called the AZ score is defined based on a clustering method
      used to recognize protein-coding genes in the A. pernix genome. The criterion for
      a coding or non-coding ORF is based on the AZ score. ORFs with AZ > 0 or AZ < 0
      are coding or non-coding, respectively. Consequently, 620 out of 632 ORFs with
      putative functions based on the original annotation are contained in cluster A,
      which have positive AZ scores. In addition, all 29 ORFs encoding putative or
      conserved proteins newly added in RefSeq annotation also have positive AZ scores.
      Accordingly, the number of re-recognized protein-coding genes in the A. pernix
      genome is 1610, which is significantly less than 2694 in the original annotation
      and also much less than 1841 in the RefSeq annotation curated by NCBI staff.
      Annotation information of re-recognized genes and their AZ scores are available
      at: http://tubic.tju.edu.cn/Aper/.

PMID- 15871460
TI  - A mutation in the serum and glucocorticoid-inducible kinase-like kinase (Sgkl)
      gene is associated with defective hair growth in mice.
AB  - YPC is a mutant mouse strain with defective hair growth characterized by thin,
      short hairs and poorly developed hair bulbs and dermal papillae. To identify the
      gene associated with the phenotype, we performed genome-wide linkage analysis
      using 1010 backcross progeny and 123 microsatellite markers covering all
      chromosomes. The mutant locus (ypc) was mapped to a 0.2-cM region in the proximal
      part of mouse chromosome 1. This 0.2-cM region corresponds to a 450-kb region of
      genome sequence that contains two genes with known functions and five ESTs or
      predicted genes with unknown functions. Sequence analysis revealed a single C-to
      A nucleotide substitution at nucleotide 1382 in the Sgkl gene, causing a nonsense
      mutation at codon 461. Sgkl encodes serum and glucocorticoid-inducible kinase
      like kinase (SGKL), which belongs to a subfamily of serine/threonine protein
      kinases and has been suggested to have a role downstream of lipid signals
      produced by activation of phosphoinositide 3-kinase (PI3K). In the mutant SGKL, a
      serine residue in the C-terminal end of the protein (Ser486), which is
      indispensable for activation of SGKL upon phosphorylation, is abolished by
      premature termination. Specific expression of the Sgkl gene in the inner root
      sheath of growing hair follicles was also identified by in situ hybridization.
      Therefore, we concluded that the nucleotide substitution in the Sgkl gene is the
      causative mutation for defective hair growth in the ypc mutant mouse and that the
      signaling pathway involving SGKL plays an essential role in mammalian hair
      development.

PMID- 15871461
TI  - An evolutionary scenario for genomic imprinting of Impact lying between
      nonimprinted neighbors.
AB  - Mouse Impact is the sole imprinted gene mapped to chromosome 18 to date. Despite
      its remarkable evolutionary conservation, human IMPACT was shown to escape
      genomic imprinting. Here we identified Hrh4 and Osbpl1 as the distal and proximal
      nearest neighbors of Impact, respectively, and found that both genes are
      expressed biallelically. Thus, in contrast with most imprinted genes, Impact
      fails to show apparent physical clustering with other imprinted genes. Since
      Impact not only lies in an intergenic region but also consists of 11 exons, it
      does not seem to be an imprinted gene generated by a retrotransposition.
      Hazardous effects of overexpressed Impact, a genomic segment containing
      paralogues of Hrh4 and Osbpl1 but not of Impact, and enhanced promoter activity
      in the mouse led us to propose an alternative model. This model assumes that
      segmental duplication followed by enhancement of the promoter activity in the
      lineage to mouse is responsible for the species-specific imprinting of Impact.

PMID- 15871462
TI  - Large-scale identification and mapping of nuclear matrix-attachment regions in
      the distal imprinted domain of mouse chromosome 7.
AB  - Mammalian imprinted genes, which are expressed from only one of the parental
      alleles, have a tendency to form clusters and are regulated by long-range
      mechanisms. Nuclear matrix-attachment regions (MARs), the anchor points of loop
      domains, are involved in coordination of gene expression and could play a role in
      regulation of imprinted domains. We have identified and mapped a total of 52 MARs
      in a 1-Mb imprinted domain on mouse distal chromosome 7 using our cosmid contigs
      and an in vitro MAR assay. We find two MAR clusters (comprising 20 and 19 MARs),
      one of which is mapped in the Th-Ins2 intergenic region, coincident with the
      boundary between the two imprinted subdomains. However, the imprinted/non
      imprinted boundaries are not associated with a MAR. Based on the sequence
      information, we find that many of the MARs are rich in long interspersed nuclear
      elements. In addition, comparisons of the results obtained with several MAR
      prediction software programs reveal good performance of ChrClass in terms of both
      sensitivity and specificity. This study presents the first large-scale mapping of
      MARs in an imprinted domain and provides a platform for understanding the roles
      of MARs in imprinting.

PMID- 15871463
TI  - High-speed conversion of cytosine to uracil in bisulfite genomic sequencing
      analysis of DNA methylation.
AB  - Bisulfite genomic sequencing is a widely used technique for analyzing cytosine
      methylation of DNA. By treating DNA with bisulfite, cytosine residues are
      deaminated to uracil, while leaving 5-methylcytosine largely intact. Subsequent
      PCR and nucleotide sequence analysis permit unequivocal determination of the
      methylation status at cytosine residues. A major caveat associated with the
      currently practiced procedure is that it takes 16-20 hr for completion of the
      conversion of cytosine to uracil. Here we report that a complete deamination of
      cytosine to uracil can be achieved in shorter periods by using a highly
      concentrated bisulfite solution at an elevated temperature. Time course
      experiments demonstrated that treating DNA with 9 M bisulfite for 20 min at 90
      degrees C or 40 min at 70 degrees C all cytosine residues in the DNA were
      converted to uracil. Under these conditions, the majority of 5-methylcytosines
      remained intact. When a high molecular weight DNA derived from a cell line
      (containing a number of genes whose methylation status was known) was treated
      with bisulfite under the above conditions and amplified and sequenced, the
      results obtained were consistent with those reported in the literature. Although
      some degradation of DNA occurred during this process, the amount of treated DNA
      required for the amplification was nearly equal to that required for the
      conventional bisulfite genomic sequencing procedure. The increased speed of DNA
      methylation analysis with this novel procedure is expected to advance various
      aspects of DNA sciences.

PMID- 15871464
TI  - Room for improvement: CMS reports 2004 payment error rate findings; OIG publishes
      recommendations for hospital compliance programs.

PMID- 15871465
TI  - EHRs, the doctor will see you now.

PMID- 15871466
TI  - The state of document management. An HIM roundtable.

PMID- 15871468
TI  - Matchmaking. An interview with John Halamka on linking patient records
      regionally.

PMID- 15871467
TI  - Physicians, Patients, and EHRs. When it comes to a consultation, is three a
      crowd?

PMID- 15871469
TI  - Project management 101. Skills for leading and working in teams, Part 4.

PMID- 15871470
TI  - Reaffirming your HIPAA compliance efforts.

PMID- 15871471
TI  - HIM role in bringing e-HIM to small practices.

PMID- 15871472
TI  - Putting the finishing touches to security--are you ready?

PMID- 15871473
TI  - Outsourcing ROI: does it make sense for you?

PMID- 15871474
TI  - Identity theft and fraud--the impact on HIM operations.

PMID- 15871475
TI  - SNOMED CT helps drive EHR success.

PMID- 15871476
TI  - Reporting the severity of decubitus ulcers.

PMID- 15871477
TI  - From policy to pixels: director finds HIM, privacy, and EHR converge.

PMID- 15871478
TI  - Early results after ProDisc-C cervical disc replacement.
AB  - OBJECT: Cervical anterior decompression and total-disc replacement is currently
      being investigated as an alternative treatment in patients with symptomatic
      intervertebral cervical spondylosis with and without radiculopathy. The authors
      prospectively investigated the safety and efficacy of using the ProDisc-C disc
      for cervical arthroplasty in the treatment of symptomatic cervical spondylosis.
      METHODS: Sixteen patients in whom a diagnosis of symptomatic cervical spondylosis
      had been established were prospectively treated with complete anterior cervical
      discectomy and ProDisc-C cervical disc arthroplasty. Overall 12 single- and four
      two-level procedures were performed (20 prostheses). Patients underwent pre- and
      multiple postoperative assessments (3 and 6 weeks and 3, 6, and 12 months). The
      median age of all patients was 50 years (range 32-60 years). Levels of surgery
      included seven C5-6, six C6-7, and three C4-5. Neck and arm pain as well as
      disability scores were significantly improved by 3 months and remained
      significantly improved at 1 year. No additional fusion surgeries were necessary
      at the affected or unaffected levels. Radiography revealed an affected disc
      motion from 4 to 12 degrees. No surgery- or device-related complications were
      documented. CONCLUSIONS: Analysis of preliminary results involving ProDisc-C
      arthroplasty indicates significant improvement in pain and functional outcome
      scores. No spontaneous fusions at the level of surgery or at adjacent levels were
      noted. Long-term follow-up studies will be necessary before more definitive
      treatment recommendations can be formulated.

PMID- 15871479
TI  - Long-term health-related quality of life outcomes following Jefferson-type burst
      fractures of the atlas.
AB  - OBJECT: The primary goal of this study was to describe the long-term health
      related quality of life (HRQOL) outcomes in patients who have suffered Jefferson
      type fractures. These outcomes were compared with matched normative HRQOL data
      and with the patient's perceptions of their HRQOL prior to the injury. Variables
      that potentially influence these HRQOL outcomes were analyzed. No standardized
      outcome assessments have been published for patients who suffer these fractures;
      their outcomes have long thought to be excellent following treatment. Determining
      the optimal surrogate measure to represent preinjury HRQOL in trauma patients is
      difficult. METHODS: A retrospective review, radiographic analysis, and cross
      sectional outcome assessment were performed. The Short Form (SF)-36 and the
      American Academy of Orthopaedic Surgeons/North American Spine Society (AAOS/NASS)
      outcome instruments were filled out by patients at final follow-up examination
      (follow-up period 75 months, range 19-198 months) to represent their current
      status as well as their perceptions of preinjury status. In 34 patients, the SF
      36 physical component score and the AAOS/NASS pain values were significantly
      lower than normative values. There was no significant difference between
      normative and preinjury values. Spence criteria greater than 7 mm and the
      presence of associated injuries predicted poorer outcome scores during the follow
      up period. CONCLUSIONS: Long-term follow-up examination of patients with
      Jefferson fractures indicated that patients' status does not return to the level
      of their perceived preinjury health status or that of normative population
      controls. Those with other injuries and significant osseous displacement (> or =
      7 mm total) may experience poorer long-term outcomes. Limitations of the study
      included a relatively low (60%) response rate and the difficulties of identifying
      an appropriate baseline outcome in a trauma population with which the follow-up
      outcomes can be compared.

PMID- 15871480
TI  - Quantitative changes in gait parameters after central corpectomy for cervical
      spondylotic myelopathy.
AB  - OBJECT: In this study, quantitative gait analysis is used to describe the changes
      in the kinematic and kinetic parameters of gait after central corpectomy in
      patients with cervical spondylotic myelopathy (CSM). METHODS: Six men with CSM
      that was categorized preoperatively as Nurick Grade 3 or 4 were assessed using
      quantitative gait analysis. The values of various kinematic and kinetic
      parameters, physiological cost index, and range of motion (ROM) in the lower-limb
      joints were computed preoperatively as well as at follow-up review 12 months or
      more postoperatively. Patients also received scores based on the Nurick and
      Japanese Orthopaedic Association (JOA) lower-limb functional scales pre- and
      postoperatively. The mean Nurick grade improved from 3.3 to 2 (p = 0.02) and the
      mean JOA lower-limb score improved from 4.2 to 6 (p = 0.02). The forward ground
      reaction force showed a statistically significant increase from 10.8+/-4.1% body
      weight to 12.1+/-3.6% body weight (p = 0.04). There was a significant improvement
      in the ROM at the knees, from 48.6+/-7.7 degrees to 54.2+/-5.2 degrees (p =
      0.03). There was an increase in the mean walking speed, stride length, percentage
      of single-limb support time, vertical and backward ground reaction forces, and
      ROM at the hips in the postoperative gait analysis. These results indicate an
      improved stability of gait as well as greater flexibility in the knee after
      decompression of the spinal cord. These changes correlated with an improvement in
      the functional status of patients with CSM after central corpectomy. CONCLUSIONS:
      Gait analysis can be used as a quantitative tool in the pre- and postoperative
      evaluation of patients with CSM.

PMID- 15871481
TI  - Dural ossification associated with cervical ossification of the posterior
      longitudinal ligament: frequency of dural ossification and comparison of
      neuroimaging modalities in ability to identify the disease.
AB  - OBJECT: The authors' goal in this study was to understand the frequency and
      pattern of dural ossification (DO, and to evaluate the effectiveness of
      neuroimaging modalities used to identify this disease in association with
      ossification of the posterior longitudinal ligament (OPLL). METHODS: One hundred
      eleven patients with OPLL underwent anterior procedures. Of these patients, 17
      (15.3%) had associated ossification of the dura mater. There were 10 cases of DO
      in the 94 patients with segmental OPLL and seven in the 17 patients with
      nonsegmental OPLL (seven continuous and 10 mixed-type OPLL). Retrospective
      evaluation of DO was performed by examining plain x-ray films, polytomography
      studies, computerized tomography (CT) scans, and magnetic resonance (MR) images.
      A positive correlation was found between the type of OPLL and the frequency of DO
      (p < 0.01). The DO was classified into the following three types according to
      shape: 1) isolated type, 2) double-layer type, and 3) en bloc type, based on its
      relationship with OPLL. There were 10 lesions of the double-layer type, four en
      bloc type, and three isolated type; the double-layer pattern of DO was the most
      common. All DOs as well as OPLLs (17 cases) were identified using bone-window CT
      scanning. Polytomography was used successfully to identify all 12 OPLLs, whereas
      DO was recognized in seven of the 12 cases. Magnetic resonance imaging could not
      identify DO (none of the 17 cases), although OPLL was identified on MR imaging in
      12 of the 17 cases. CONCLUSIONS: Three patterns of DO associated with OPLL, that
      is, isolated, double-layer, and en bloc types, were confirmed by retrospective
      analysis of neuroimaging findings. Nonsegmental OPLL was likely to be accompanied
      by DO. Bone-window CT scanning was most useful for identification of DO as well
      as OPLL, whereas MR imaging was ineffective in recognizing DO.

PMID- 15871482
TI  - Technical advantages of an ultrasonic bone curette in spinal surgery.
AB  - OBJECT: The authors discuss the safety and efficacy of an ultrasonic bone curette
      in various spinal surgeries and report its advantages in clinical application.
      METHODS: Between April 2002 and September 2003, 76 patients with various spinal
      diseases (29 cervical, five thoracic, 40 lumbosacral, and two foramen magnum
      regions) were treated microsurgically by using a Sonopet ultrasonic bone curette
      with longitudinal and torsional tips and lightweight handpieces. The operations
      were performed successfully and the device was easy to handle. There were no
      instrument-related complications or -induced damage to any structure even when
      removing osseous spurs or ossified lesions near the dura mater, nerves, and
      vessels. CONCLUSIONS: The ultrasonic curette is a useful instrument for
      procedures performed near the dura mater or other neural tissue without excessive
      heat production or mechanical injury. This device is recommended for various
      spinal surgeries in addition to high-speed drills or other tools.

PMID- 15871483
TI  - Percutaneous vertebroplasty and kyphoplasty performed at a cancer center:
      refuting proposed contraindications.
AB  - OBJECT: The purpose of this study was to examine a group of patients with cancer
      who underwent a vertebroplasty or a kyphoplasty for a vertebral body (VB)
      fracture, even though the procedure may have been considered contraindicated
      based on previous reports in the literature. METHODS: The electronic database
      maintained by the Departments of Neurosurgery and Anesthesiology-Pain Management
      at the University of Texas M. D. Anderson Cancer Center was searched for patients
      who underwent vertebroplasty or kyphoplasty between January 2001 and July 2003.
      The criteria defining a contraindicated procedure were based on a review of the
      literature. Group I consisted of patients who did not undergo a contraindicated
      vertebroplasty or kyphoplasty, whereas Group II consisted of patients who
      underwent one of these procedures even though it may have been considered
      contraindicated. There were 53 patients with fractures at 132 levels who met the
      criteria for the study. Of these, 17 patients with fractures at 18 levels (14% of
      total) were considered to have undergone a contraindicated vertebroplasty or
      kyphoplasty (Group II). There were 12 complications (11%) in the 114 levels in
      Group I and seven complications (39%) in the 18 levels in Group II (p = 0.03).
      The most common complication was cement extrusion from the anterior VB that did
      not involve the venous system. No patient required an open surgical procedure to
      remove extruded cement. CONCLUSIONS: Vertebroplasty and kyphoplasty appear to be
      safe and effective in the setting of severe back pain caused by VB fracture that
      is unresponsive to other therapies, even in the presence of relative
      contraindications to the procedures.

PMID- 15871484
TI  - New treatment of lumbar disc herniation involving 5-hydroxytryptamine2A receptor
      inhibitor: a randomized controlled trial.
AB  - OBJECT: Serotonin or 5-hydroxytryptamine (5-HT) is a chemical mediator associated
      with nucleus pulposus-induced radiculopathy. Inhibition of 5-HT receptors may
      potentially alleviate symptoms in patients with lumbar disc herniation. This
      prospective randomized controlled study was performed to evaluate the efficacy of
      the 5-HT2A receptor inhibitor in the treatment of symptomatic lumbar disc
      herniation. METHODS: Forty patients with sciatica due to L4-5 or L5-S1 disc
      herniation were randomly allocated to treatment with the 5-HT2A inhibitor
      (sarpogrelate 300 mg/day) or nonsteroidal antiinflammatory drugs (NSAIDs;
      diclofenac 75 mg/day). Low-back pain, leg pain, and numbness were evaluated using
      a visual analog scale (VAS) before and after a 2-week course of treatment. The
      patients received only allocated medicine during the 2-week regimen and were
      thereafter allowed to choose any treatment options depending on their residual
      symptoms. One-year clinical outcomes were assessed based on the rates of
      additional medical interventions. The mean VAS score improvements in the 5-HT2A
      and NSAID groups were 33 and 46% for low-back pain, 32 and 32% for leg pain, and
      35 and 22% for leg numbness, respectively. After the 2-week regimen, no
      additional medical interventions were required in 50% of 5-HT2A-treated patients
      and 15% of those receiving NSAIDs. Epidural or nerve root block procedures were
      performed in 35% of the 5-HT2A group and 45% of the NSAID group. Surgery was
      required in 20% of the 5-HT2A group and 30% of the NSAID group patients.
      CONCLUSIONS: The current study provided evidence that the efficacy of the 5-HT2A
      inhibitor was comparable with that of NSAID therapy for lumbar disc herniation.
      The 5-HT2A inhibitor has the potential to alleviate symptoms in patients with
      lumbar disc herniation.

PMID- 15871485
TI  - Spinal extradural schwannoma.
AB  - OBJECT: The authors endeavor to define the clinical and surgery-related profile
      of spinal nerve sheath tumors located in the extradural space outside both the
      dural sac and, apparently, the nerve roots' sleeve. METHODS: A series of 24
      extradural schwannomas was retrospectively selected after reviewing the notes of
      spinal nerve sheath tumors surgically treated at La Sapienza University of Rome.
      Clinical data, tumor-related characteristics, and outcome were analyzed. Women
      predominantly harbored these tumors. On admission sensory nerve root dysfunction
      was infrequently reported, whereas pyramidal tract deficits were often present.
      The tumor, generally large, was most frequently located in the intermediate
      thoracic segments and high cervical region; only one was reported in the
      lumbosacral region. Considerable erosion of vertebral bodies was reported in
      almost one third of the cases. In four patients eloquent nerve roots, that of C-5
      in three and that of S-1 in one, were involved with the tumor. Radical tumor
      resection, with preservation of the nerve roots, was possible in several cases,
      whereas in two patients manipulation and resection of the C-5 root produced
      transient and permanent, respectively, root palsy. At follow-up examination
      patients for whom walking was impossible before surgery were now able to walk.
      CONCLUSIONS: Extradural schwannomas can be distinguished from other nerve sheath
      tumors growing inside the spinal canal by their clinicoradiological features and
      unlikely nerve root origin. After surgery, recovery from pyramidal tract
      deficits, even severe, is noteworthy; in the authors' experience, however,
      resection of an involved appendicular root is more likely to result in a
      permanent and significant radicular deficit.

PMID- 15871486
TI  - A three-dimensional collagen matrix as a suitable culture system for the
      comparison of cyclic strain and hydrostatic pressure effects on intervertebral
      disc cells.
AB  - OBJECT: To study intervertebral disc cell mechanobiology, the authors developed
      experimental systems that allow the application of cyclic strain and intermittent
      hydrostatic pressure (IHP) on isolated disc cells under equal three-dimensional
      (3D) culture conditions. The purpose of the study was to characterize disc cell
      proliferation, viability, morphology, and gene expression in 3D collagen
      matrices. METHODS: The effects of cyclic strain (1, 2, 4, and 8% strain; 1 Hz)
      and IHP (0.25 MPa, 0.1 Hz) on gene expression (real-time polymerase chain
      reaction) of anabolic and catabolic matrix proteins were investigated and
      compared with those derived from mechanically unstimulated controls.
      Intervertebral disc cells proliferated in the collagen gels (mean viability
      91.6%) and expressed messenger RNA for collagen I, collagen II, aggrecan, matrix
      metalloproteinase (MMP)-2, and MMP-3. Morphologically, both spindle-shaped cells
      with longer processes and rounded cells were detected in the collagen scaffolds.
      Cyclic strain increased collagen II and aggrecan expression and decreased MMP-3
      expression of anulus fibrosus cells. No significant difference between the four
      strain magnitudes was found. Intermittent hydrostatic pressure tended to increase
      collagen I and aggrecan expression of nucleus cells and significantly decreased
      MMP-2 and -3 expression of nucleus cells, whereas aggrecan expression of anulus
      cells tended to decrease. CONCLUSIONS: Based on these results, the collagen
      matrix appeared to be a suitable substrate to apply both cyclic strain and IHP to
      intervertebral disc cells under 3D culture conditions. Individual variations may
      be influenced by the extent of degeneration of the disc specimens from which the
      cells were isolated. This experimental setup may be suitable for studying the
      influence of degeneration on the disc cell response to mechanical stimuli.

PMID- 15871487
TI  - A novel dynamic model for experimental spinal cord compression.
AB  - OBJECT: The goal of this study was to develop a novel dynamic model for
      experimental spinal cord compression that closely approximates neoplastic
      epidural compression of the spinal cord in humans. METHODS: In 30 New Zealand
      white rabbits, the thoracic spine was exposed via a posterior approach. On each
      side of one vertebral lamina a small hole was drilled caudal to the articular
      process. A silicone band was passed through these holes, forming a loop. The
      spinal dura mater was exposed via an interlaminar approach. The loop was brought
      into contact with the dura mater and fixed in its position encircling 270 degrees
      of the circumference of the spinal cord. Thereafter, the loop was gradually
      tightened at set times by pulling at the ends of the band and fixing them again
      in their new position. The spinal cord was thus increasingly compressed in a
      circular and dynamic manner. Neurological deficits of various degrees were
      created in all animals in the compression group, and the compressive effect of
      the loop was reliably demonstrated on MR imaging. After decompression of the
      spinal cord, the neurological deficits were reversible in the majority of
      animals, and MR imaging revealed either no signal changes or only circumscribed
      ones within the cord. In contrast, MR images obtained in animals that did not
      recover revealed the occurrence of extensive chronic myelopathy. CONCLUSIONS:
      This novel model features reproducibility of paresis and neurological recovery.
      It is a dynamic model simulating circular tumor growth and is characterized by
      its easy, straightforward, and cost-saving applicability.

PMID- 15871488
TI  - Spinal nerve root ganglionitis as a cause of disc herniation: case report.
AB  - The authors report on a patient in whom monoradicular pain was caused by
      ganglionitis of a spinal nerve. Neuroimaging and intraoperative findings
      identified what were thought to be tumorlike changes in the affected nerve root.
      The neuropathological examination, however, revealed typical signs of
      ganglionitis. This rare inflammation usually appears with viral infections, as
      part of paraneoplastic symptoms, or in the presence of Sjogren disease. Because
      all of these differential diagnoses were negative in the treated patient, chronic
      nerve root compression due to disc herniation was suspected as the causative
      factor for the spinal ganglionitis.

PMID- 15871489
TI  - Charcot arthropathy in relation to autonomic dysreflexia in spinal cord injury:
      case report and review of the literature.
AB  - Charcot spinal arthropathy has been described as a late complication of spinal
      cord injury. In patients with these injuries in whom the spine below the level of
      injury is insensate, joint trauma can progress until spinal instability ensues.
      The authors describe the case of a 50-year-old man with complete C-8 tetraplegia
      who experienced a 4-month history of episodic severe headaches, profuse sweating
      over his face and arms, and episodic severe hypertension in addition to a
      "grinding" sensation in the lower back. Charcot arthropathy at the T11-12 levels
      with pathological mobility was demonstrated on neuroimaging. Intraoperatively, a
      complete spinal cord transection was identified. Anterior and posterior
      thoracolumbar fusion across the mobile segment resulted in complete amelioration
      of signs and symptoms of autonomic dysreflexia. This entity, a common condition
      in the setting of spinal cord injury, has many triggers. Definitive treatment is
      targeted at the removal of the underlying cause. As demonstrated here, Charcot
      spinal arthropathy can act as a powerful trigger for induction of autonomic
      dysreflexia. Treatment of the associated spinal instability resulted in
      eradication of all signs and symptoms of the dysreflexia.

PMID- 15871490
TI  - Type II odontoid fracture from frontal impact: case report and biomechanical
      mechanism of injury.
AB  - The authors report a case of Type II odontoid fracture from a frontal impact
      sustained in the crash of a late-model motor vehicle. They discuss the
      biomechanical mechanisms of injury after considering patient demographic data,
      type and use of restraint systems including seatbelt and airbags, crash
      characteristics, and laboratory-based experimental studies. Multiple factors
      contributed to the Type II odontoid fracture: the patient's tall stature and
      intoxicated state; lack of manual three-point seat belt use; obliqueness of the
      frontal impact; and the most likely preflexed position of the head-neck complex
      at the time of impact, which led to contact of the parietal region with the A
      pillar roof-rail area of the vehicle and resulted in the transfer of the dynamic
      compressive force associated with lateral bending. Odontoid fractures still occur
      in individuals involved in late-model motor vehicle frontal crashes, and because
      this injury occurs secondary to head impact, airbags may not play a major role in
      mitigating this type of trauma to an unrestrained occupant. It may be more
      important to use seat belts than to depend on the airbag alone for protection
      from injury.

PMID- 15871491
TI  - Postangiographic thrombosis of a spinal arteriovenous malformation: case report.
AB  - The authors report the case of a 30-year-old man who presented with progressive
      neurological deficits due to a spinal arteriovenous malformation (AVM). There was
      sudden increase in his neurological deficits after diagnostic angiography was
      performed. Repeated magnetic resonance imaging and angiography revealed complete
      thrombosis of the malformation. Stenosis in the draining vein was the most
      probable cause of this postangiographic occlusion of the AVM. Contrast injection
      during angiography may have precipitated the thrombosis.

PMID- 15871492
TI  - Asymptomatic spherocytosis presenting with spinal cord compression: case report.
AB  - Extramedullary hematopoiesis (EMH) is a compensatory mechanism occurring in
      patients with chronic anemia, which occurs most frequently with thalassemia. The
      authors report the case of a 57-year-old man, with no history of clinical or
      hematological disease, presenting with spinal cord compression. Magnetic
      resonance (MR) imaging demonstrated a homogeneous posterior epidural mass
      extending from T-3 to T-6. Following decompressive surgery, the patient's
      symptoms improved. Histological analysis showed features consistent with a
      diagnosis of EMH. Subsequent workup was remarkable for an asymptomatic
      spherocytosis without anemia. There was no family history of anemia. An EMH
      related presentation of mild spherocytosis has been described in the literature,
      but its epidural location led to spinal cord compression. The MR imaging features
      were suggestive of EMH, but in the presence of spinal cord compression and in the
      absence of a history of chronic anemia, the authors did not believe that
      nonsurgical management would have been reasonable.

PMID- 15871493
TI  - Ligamentum flavum hematoma in the rigid thoracic spinal segments: case report.
AB  - Ligamentum flavum hematoma, a rare cause of spinal nerve root and canal
      compression, typically occurs in the mobile lumbar spine segments. A thoracic
      ligamentum flavum hematoma is extremely rare--only one such case of a
      thoracolumbar (T11-12) lesion has been reported. The thoracolumbar region with
      its floating ribs, however, is structurally and biomechanically similar to the
      lumbar spine and its mobility is greater than the higher thoracic levels. To the
      best of their knowledge, the authors report the first case of a ligamentum flavum
      hematoma in the region of the rigid thoracic spinal segments with the contiguous
      rib cage. A symptomatic T9-10 ligamentum flavum hematoma is described in the case
      of a 66-year-old woman with compensatory thoracic lordosis secondary to the
      lumbar degenerative kyphosis. The hematoma was removed and the diagnosis was
      histologically confirmed. The authors speculate that thoracic lordosis might have
      contributed to the development of the hematoma because the ligamentum flavum and
      the facet joint were subjected to greater axial stress than in individuals with
      normal spinal alignment.

PMID- 15871494
TI  - Use of percutaneous endoscopy to place syringopleural or cystoperitoneal
      cerebrospinal fluid shunts: technical note.
AB  - The authors describe a technique for percutaneous endoscopic shunt placement to
      treat clinically symptomatic spinal cysts. Seven patients underwent the procedure
      -five with syringomyelia, one with a symptomatic perineurial cyst, and one with a
      large arachnoid cyst. In all patients the shunt was successfully placed, and
      clinical improvement occurred in six. In four patients the entire procedure was
      performed endoscopically, whereas in three conversion to an open surgical
      exposure was required for safe access of a syrinx cavity. Overall, however, the
      pleural or peritoneal catheter was successfully placed endoscopically in all
      seven patients. There were two cases of postoperative positional headaches of
      which one required valve revision. In one case the catheter migrated and required
      repositioning. Percutaneous endoscopic shunt placement appears feasible in
      appropriately selected patients.

PMID- 15871495
TI  - Reduction of fixed atlantoaxial dislocation in 24 cases: technical note.
AB  - The authors describe an alternative method of C1-2 joint distraction, reduction,
      and fixation in the treatment of 24 patients with fixed atlantoaxial dislocation.
      Based on their results, they conclude that there is a place for reduction of
      fixed atlantoaxial dislocation and subsequent fixation in a procedure that does
      not require removal of any osseous spinal element.

PMID- 15871496
TI  - Fibrous dysplasia.

PMID- 15871497
TI  - Comments on the unruptured aneurysm study from Japan; does this study clarify
      what to do?

PMID- 15871498
TI  - The risk of rupture of unruptured cerebral aneurysms in the Japanese population:
      a systematic review of the literature from Japan by Morita, et al.

PMID- 15871499
TI  - Cushing and Bovie: lessons learned.

PMID- 15871500
TI  - Risk of rupture associated with intact cerebral aneurysms in the Japanese
      population: a systematic review of the literature from Japan.
AB  - OBJECT: Knowing the rate of rupture associated with unruptured cerebral aneurysms
      (UCAs) can help surgeons determine a case management strategy in patients
      harboring these lesions. According to large-scale cohort studies involving
      populations in North America and Europe, small unruptured aneurysms carry a very
      low risk of rupture. In Japan, however, there have been sporadic reports of
      higher rates of rupture. To identify the rupture risk associated with UCAs in the
      Japanese population, the authors systematically reviewed retrospective studies of
      the natural course of these lesions. METHODS: The authors searched Medline and
      the Japan Medical Abstract Society Index for reports of UCAs in Japan. Two of the
      authors verified the eligibility of the reports and extracted data independently.
      Additional information was directly obtained from the authors of the original
      reports. Thirteen reports covering a total of 3801 patient-years fulfilled the
      criteria for our study. Subsequent rupture was documented in 104 patients and the
      annual rupture rate was 2.7% (95% confidence interval 2.2-3.3%). Large, posterior
      circulation, and symptomatic aneurysms were associated with significantly higher
      rates of rupture (relative risks 6.4, 2.3, and 2.1, respectively). The risk of
      rupture determined by the authors' review was significantly higher than that
      reported by investigators from international cohort studies. CONCLUSIONS:
      Although a selection bias of patients may be the cause of the higher rupture
      risk, untreated UCAs that have been followed in Japanese institutions have a
      considerably high rate of rupture. The natural course of UCAs should be carefully
      estimated in countries not included in the international studies.

PMID- 15871501
TI  - Endovascular coil embolization of intracranial aneurysms: important factors
      related to rates and outcomes of incomplete occlusion.
AB  - OBJECT: The authors report on important factors that influenced clinical and
      angiographically demonstrated outcomes in patients treated using coil
      embolization. METHODS: This study included 160 consecutive patients who underwent
      endovascular coil embolization for treatment of intracranial aneurysms.
      Univariate and multivariate logistic regression analyses were performed to assess
      factors that influenced the immediate posttreatment angiographic result. Cox
      regression analysis was used to establish factors related to the occurrence of
      negative events as well as a curve indicating the time to a negative event.
      Negative events were defined as aneurysm remnant increase, repeated treatment,
      rebleeding, or death during periprocedural hospitalization. Seventy-three percent
      of the patients treated in this study were independent or demonstrated no deficit
      (Glasgow Outcome Scale [GOS] Score 4 or 5) at a mean follow up of 18.2 months.
      The annual delayed rebleeding rate was 0.45%. Fifty percent of patients (65 of
      131) suffered a negative event within 13 +/- 14 months (standard deviation).
      Statistically significant factors associated with the occurrence of negative
      events were rupture status (p = 0.0128) and immediate posttreatment angiographic
      result (p < 0.001). Overall clinical outcome assessed using the GOS was
      significantly related to the immediate posttreatment angiographic result (chi2 =
      4.788, p = 0.029). The immediate post-treatment angiographic results were
      significantly influenced by catheter stability (p = 0.0012), aneurysm geometry
      (that is, simple or complex, p = 0.0053), and aneurysm neck diameter (p =
      0.0205). CONCLUSIONS: A good or excellent clinical outcome can be obtained in
      most patients treated using endovascular coil embolization of intracranial
      aneurysms. Note, however, that a significant number of patients treated using
      traditional platinum coils will harbor unstable aneurysm remnants or require
      repeated treatment.

PMID- 15871502
TI  - Safety of intracranial aneurysm surgery performed in a postgraduate training
      program: implications for training.
AB  - OBJECT: Patient care and educational experience have long formed a dichotomy in
      modem surgical training. In neurosurgery, achieving a delicate balance between
      these two factors has been challenged by recent trends in the field including
      increased subspecialization, emerging technologies, and decreased resident work
      hours. In this study the authors evaluated the experience profiles of
      neurosurgical trainees at a large Canadian academic center and the safety of
      their practice on patient care. METHODS: Two hundred ninety-three patients who
      underwent surgery for intracranial aneurysm clipping between 1993 and 1996 were
      selected. Prospective data were available in 167 cases, allowing the operating
      surgeon to be identified. Postoperative data and follow-up data were gathered
      retrospectively to measure patient outcomes. In 167 cases, a total of 183
      aneurysms were clipped, the majority (91%) by neurosurgical trainees. Trainees
      performed dissections on aneurysms that were predominantly small (< 1.5 cm in
      diameter; 77% of patients) and ruptured (64% of patients). Overall mortality
      rates for the patients treated by the trainee group were 4% (two of 52 patients)
      and 9% (nine of 100 patients) for unruptured and ruptured aneurysm cases,
      respectively. Patient outcomes were comparable to those reported in historical
      data. Staff members appeared to be primary surgeons in a select subset of cases.
      CONCLUSIONS: Neurosurgical trainees at this institution are exposed to a broad
      spectrum of intracranial aneurysms, although some case selection does occur. With
      careful supervision, intracranial aneurysm surgery can be safely delegated to
      trainees without compromising patient outcomes. Current trends in practice
      patterns in neurosurgery mandate ongoing monitoring of residents' operative
      experience while ensuring continued excellence in patient care.

PMID- 15871503
TI  - Prognostic significance of intracranial dissemination of glioblastoma multiforme
      in adults.
AB  - OBJECT: The clinical outcome and treatment of adult patients with disseminated
      intracranial glioblastoma multiforme (GBM) is unclear. The objective in the
      present study was to assess the prognostic significance of disseminated
      intracranial GBM in adults at presentation and at the time of tumor progression.
      METHODS: Clinical data from 1491 patients older than 17 years and harboring a GBM
      that had been diagnosed between 1988 and 1998 at the University of California at
      San Francisco neurooncology clinic were retrospectively reviewed. Dissemination
      of the GBM (126 patients) was determined based on Gd-enhanced magnetic resonance
      images. Classification of dissemination was as follows: Type I, single lesion
      with subependymal or subarachnoid spread; Type II, multifocal lesions without
      subependymal or subarachnoid spread; and Type III, multifocal lesions with
      subependymal or subarachnoid spread. Subgroups of patients were compared using
      Kaplan-Meier curves that depicted survival probability. The median
      postprogression survival (PPS), defined according to neuroimaging demonstrated
      dissemination, was 37 weeks for Type I (23 patients), 25 weeks for Type II (50
      patients), and 10 weeks for Type III spread (19 patients). Patients with
      dissemination at first tumor progression (52 patients) overall had a shorter PPS
      than those in a control group with local progression, after adjusting for age,
      Kamofsky Performance Scale score, and time from tumor diagnosis to its
      progression (311 patients). When analyzed according to tumor dissemination type,
      PPS was significantly shorter in patients with Type II (33 patients, p < 0.01)
      and Type III spread (11 patients, p < 0.01) but not in those with Type I spread
      (eight patients, p = 0.18). CONCLUSIONS: Apparently, the presence of intracranial
      tumor dissemination on initial diagnosis does not in itself preclude aggressive
      treatment if a patient is otherwise well. A single focus of GBM that later
      demonstrates Type I dissemination on progression does not have a worse prognosis
      than a lesion that exhibits only local recurrence.

PMID- 15871504
TI  - Is gross-total resection sufficient treatment for posterior fossa ependymomas?
AB  - OBJECT: The goals of this study were to analyze outcomes in patients with
      posterior fossa ependymomas, determine whether gross-total resection (GTR) alone
      is appropriate treatment, and evaluate the role of radiation therapy. METHODS:
      All patients with newly diagnosed intracranial ependymomas treated at Barrow
      Neurological Institute between 1983 and 2002 were identified. Those with
      supratentorial primary lesions, subependymomas, or neuraxis dissemination were
      excluded. Forty-five patients met the criteria for the study. Gross-total
      resection was accomplished in 32 patients (71%) and subtotal resection (STR) in
      13 (29%). Radiation therapy was given to 25 patients: 13 following GTR and 12
      after STR. The radiation fields were craniospinal followed by a posterior fossa
      boost in six patients and posterior fossa or local only in the remaining
      patients. With a median follow-up period of 66 months, the median duration of
      local control was 73.5 months with GTR alone, but has not yet been reached for
      patients with both GTR and radiotherapy (p = 0.020). The median duration of local
      control following STR and radiotherapy was 79.6 months. The 10-year actuarial
      local control rate was 100% for patients who underwent GTR and radiotherapy, 50%
      for those who underwent GTR alone, and 36% for those who underwent both STR and
      radiotherapy, representing significant differences between the GTR-plus
      radiotherapy and GTR-alone cohorts (p = 0.018), and between the GTR-plus
      radiotherapy and the STR-plus-radiotherapy group (p = 0.003). There was no
      significant difference in the 10-year actuarial local control rate between the
      GTR-alone and STR-plus-radiotherapy cohorts (p = 0.370). The 10-year overall
      survival was numerically superior in patients who underwent both GTR and
      radiotherapy: 83% compared with 67% in those who underwent GTR alone and 43% in
      those who underwent both STR and radiotherapy. These differences did not achieve
      statistical significance. Univariate analyses revealed that radiotherapy, tumor
      grade, and extent of resection were significant predictors of local control.
      CONCLUSIONS: Gross-total resection should be the intent of surgery when it can be
      accomplished with an acceptable degree of morbidity. Even after GTR has been
      confirmed with postoperative imaging, however, adjuvant radiotherapy
      significantly improves local control. The authors currently recommend the use of
      postoperative radiotherapy, regardless of whether the resection is gross total or
      subtotal.

PMID- 15871505
TI  - Intraoperative auditory brainstem responses in patients with cerebellopontine
      angle meningiomas involving the inner auditory canal: analysis of the predictive
      value of the responses.
AB  - OBJECT: Meningiomas of the cerebellopontine angle (CPA) can either arise from or
      secondarily grow into the inner auditory canal (IAC). This location may have a
      great impact on hearing function following surgery to remove these lesions. The
      aim of this retrospective study was to investigate the reliability and predictive
      importance of auditory brainstem responses (ABRs) for the determination of
      postoperative auditory function in patients with CPA meningiomas in comparison
      with results obtained in patients who undergo surgery for vestibular schwannomas.
      METHODS: In a consecutive series of 1800 meningiomas surgically treated between
      1978 and 2002, 421 lesions were located in the CPA. In 38 patients with CPA
      meningiomas involving the IAC, the findings of intraoperative ABR monitoring and
      the hearing status of each patient before and after surgery were retrospectively
      analyzed. On analysis, ABR monitoring demonstrated stable findings in 24 patients
      throughout tumor resection and fluctuating signals in 10 patients. Among the 24
      patients with stable ABRs, postoperative hearing function improved in three
      patients, remained the same in 15, and worsened in six patients, including one
      patient who displayed postoperative deafness. There was even one patient
      recovering from preoperative deafness. Among the 10 patients with unstable ABRs,
      intermittent decreases in amplitude and deformations of variable duration in the
      ABR wave were noted. The risk of deafness was considerably higher in patients
      with prolonged phases of intermittent ABR deterioration. CONCLUSIONS: The
      presence and absence of ABRs during surgery for CPA meningiomas reliably
      predicted the presence and absence of postoperative auditory function.
      Intermittent deterioration of ABRs may result in postoperative deafness,
      depending on the duration of these events during surgery. Improvements in hearing
      are only seen when the ABRs are stable for amplitudes and latencies throughout
      surgery.

PMID- 15871506
TI  - Resection of large vestibular schwannomas: facial nerve preservation in the
      context of surgical approach and patient-assessed outcome.
AB  - OBJECT: Vestibular schwannoma surgery has evolved as new therapeutic options have
      emerged, patients' expectations have risen, and the psychological effect of
      facial nerve paralysis has been studied. For large vestibular schwannomas for
      which extirpation is the primary therapy, the goals remain complete tumor
      resection and maintenance of normal neurological function. Improved microsurgical
      techniques and intraoperative facial nerve monitoring have decreased the
      complication rate and increased the likelihood of normal to near-normal
      postoperative facial function. Nevertheless, the impairment most frequently
      reported by patients as an adverse effect of surgery continues to be facial nerve
      paralysis. In addition, patient assessment has provided a different, less
      optimistic view of outcome. The authors evaluated the extent of facial function,
      timing of facial nerve recovery, patients' perceptions of this recovery and
      function, and the prognostic value of intraoperative facial nerve monitoring
      following resection of large vestibular schwannomas; they then analyzed these
      results with respect to different surgical approaches. METHODS: The authors
      retrospectively reviewed a database of 67 patients with 71 vestibular schwannomas
      measuring 3 cm or larger in diameter. The patients had undergone surgery via
      translabyrinthine, retrosigmoid, or combined approaches. Clinical outcomes were
      analyzed with respect to intraoperative facial nerve activity, responses to
      intraoperative stimulation, and time course of recovery. Eighty percent of
      patients obtained normal to near-normal facial function (House-Brackmann Grades I
      and II). Patients' perceptions of facial nerve function and recovery correlated
      well with the clinical observations. CONCLUSIONS: Trends in the data lead the
      authors to suggest that a retrosigmoid exposure, alone or in combination with a
      translabyrinthine approach, offers the best chance of facial nerve preservation
      in patients with large vestibular schwannomas.

PMID- 15871507
TI  - Long-term neurological, visual, and endocrine outcomes following transnasal
      resection of craniopharyngioma.
AB  - OBJECT: The authors report on a cohort of patients with craniopharyngioma treated
      principally through transnasal (TN) resection and followed up for a minimum of 5
      years. More specifically, they evaluate the role of the TN approach in the
      management of craniopharyngioma. METHODS: Between 1984 and 1994, 68 patients
      underwent TN resection of craniopharyngiomas at the University of Southern
      California. The tumor was at least partially cystic in 88% of cases. Four tumors
      were purely intrasellar, 53 had intra- and suprasellar components, and 11 were
      exclusively suprasellar. During the same period, 18 patients underwent
      transcranial (TC) resection of purely suprasellar craniopharyngiomas. Long-term
      neurological, visual, and endocrine outcomes were reviewed for all patients. In
      61 (90%) of 68 patients in the TN group, total resection was achieved, according
      to 3-month postoperative magnetic resonance images, although four patients
      suffered a recurrence. Three (43%) of the seven tumors that had been partially
      resected were enlarged on serial imaging. Fifty-four (87%) of 62 patients with
      preoperative visual loss experienced improvement in one or both eyes, but two
      patients (3%) with exclusively suprasellar tumors experienced postoperative
      visual worsening in one or both eyes. New instances of postoperative
      endocrinopathy (that is, not present preoperatively) occurred as follows:
      hypogonadism (eight of 22 cases), growth hormone (GH) deficiency (four of 18
      cases), hypothyroidism (11 of 49 cases), hypocortisolemia (nine of 52 cases), and
      diabetes insipidus (DI; four of 61 cases). One case each of hypocortisolemia and
      hypothyroidism resolved after surgery. Hyperphagia occurred in 27 (40%) of 68
      patients. One patient had short-term memory loss. Postoperative complications
      included one case of cerebrospinal fluid leak. Among the 18 patients in the TC
      group, 11 had complete resections. In one case (9%) the tumors recurred. Three
      (43%) of the seven subtotally resected tumors grew during the follow-up interval.
      Vision improved in 11 (61%) of 18 cases and worsened in three (17%) as a result
      of surgery. New instances of postoperative endocrinopathy occurred as follows:
      hypogonadism (one of six cases), GH deficiency (four of seven cases),
      hypothyroidism (11 of 14 cases), hypocortisolemia (eight of 15 cases), and DI
      (nine of 16 cases). No instance of preoperative endocrinopathy was corrected
      through TC surgery. Four patients (22%) exhibited short-term memory loss and 11
      (61%) had hyperphagia after surgery. When compared with those in the TC group,
      patients in the TN group had shorter hospital stays. CONCLUSIONS: Use of the TN
      approach can render good outcomes in properly selected patients with
      craniopharyngioma, particularly when the tumor is cystic. Even in mostly
      suprasellar cases, an extended TN approach can afford complete resection. Note
      that endocrine function often worsens after surgery and that postoperative
      obesity can be a significant problem.

PMID- 15871508
TI  - High-resolution three-dimensional T2-weighted sequence for neuronavigation: a new
      setup and clinical trial.
AB  - OBJECT: Conventional imaging for neuronavigation is performed using high
      resolution computerized tomography (CT) scanning or a T1-weighted isovoxel
      magnetic resonance (MR) sequence. The extension of some lesions, however, is
      depicted much better on T2-weighted MR images. A possible fusion process used to
      match low-resolution T2-weighted MR image set with a referenced CT or T1-weighted
      data set leads to poor resolution in the three-dimensional (3D) reconstruction
      and decreases accuracy, which is unacceptable for neuronavigation. The object of
      this work was to develop a 3D T2-weighted isovoxel sequence (3D turbo-spin echo
      [TSE]) for image-guided neuronavigation of the whole brain and to evaluate its
      clinical application. METHODS: The authors performed a phantom study and a
      clinical trial on a newly developed T2-weighted isovoxel sequence, 3D TSE, for
      image-guided neuronavigation using a common 1.5-tesla MR imager (Siemens Sonata
      whole-body imager). The accuracy study and intraoperative image guidance were
      performed with the aid of the pointer-based Medtronic Stealth Station Treon. The
      3D TSE data set was easily applied to the navigational setup and demonstrated a
      high registration accuracy during the experimental trial and during an initial
      prospective clinical trial in 25 patients. The sequence displayed common
      disposable skin fiducial markers and provided convincing delineation of lesions
      that appear hyperintense on T2-weighted images such as low-grade gliomas and
      cavernomas in its clinical application. CONCLUSIONS: Three-dimensional TSE
      imaging broadens the spectrum of navigational and intraoperative data sets,
      especially for lesions that appear hyperintense on T2-weighted images. The
      accuracy of its registration is very reliable and it enables high-resolution
      reconstruction in any orientation, maintaining the advantages of image-guided
      surgery.

PMID- 15871509
TI  - Combined use of tractography-integrated functional neuronavigation and direct
      fiber stimulation.
AB  - OBJECT: The aim of this study was better preoperative planning and direct
      application to intraoperative procedures through accurate coregistration of
      diffusion-tensor (DT) imaging-based tractography results and anatomical three
      dimensional magnetic resonance images and subsequent importation of the combined
      images to a neuronavigation system (functional neuronavigation). METHODS: Six
      patients with brain lesions adjacent to the corticospinal tract (CST) were
      studied. During surgery, direct fiber stimulation was used to evoke motor
      responses to confirm the accuracy of CST depicted on functional neuronavigation.
      In three patients, stimulation of the supposed CST elicited the expected motor
      evoked potentials. In the other three, stimulation at the resection borders more
      than 1 cm away from the supposed CST showed no motor response. All patients
      underwent appropriate tumor resection with preservation of the CST. CONCLUSIONS:
      Integration of the DT imaging-based tractography information into a traditional
      neuronavigation system demonstrated spatial relationships between lesions and the
      CST, allowing for the avoidance of tract injury during lesion resection. Direct
      fiber stimulation was used for real-time reliable white matter mapping, which
      served to adjust for any discrepancy between the neuronavigation system data and
      potentially shifted positions of the brain structures. The combination of these
      techniques enabled the authors to identify accurate positions of the CST during
      surgery and to accomplish optimal tumor resections.

PMID- 15871510
TI  - Integration of three-dimensional corticospinal tractography into treatment
      planning for gamma knife surgery.
AB  - OBJECT: In the radiosurgical treatment of critically located lesions, the effort
      to minimize the risk of complication is essential. In this study the integration
      of diffusion-tensor (DT) imaging-based tractography was clinically applied to
      treatment planning for gamma knife surgery (GKS). METHODS: Seven patients with
      cerebral arteriovenous malformations located adjacent to the corticospinal tract
      (CST) underwent this technique. Data provided by DT imaging were acquired before
      the frame was affixed to the patient's head and the CST of the DT tractography
      was created using our original software. Stereotactic three-dimensional imaging
      studies were obtained after frame fixation and then coregistered with the data
      from DT tractography. After image fusion of the two studies, the combined images
      were transported to a GKS treatment-planning workstation. The spatial
      relationship between the dose distribution and the CST was clearly demonstrated
      within the 2 hours it took to complete the entire imaging process. The univariate
      logistic regression analysis of transient or permanent motor complications
      revealed a significant independent correlation with the volume of the CST that
      received 25 Gy or more and with a maximum dose to the CST (p < 0.05).
      CONCLUSIONS: The integration of DT tractography into the GKS treatment planning
      was highly useful in confirming the dose to the CST during treatment planning.

PMID- 15871511
TI  - Stereotactic radiosurgery for pituitary adenomas: an intermediate review of its
      safety, efficacy, and role in the neurosurgical treatment armamentarium.
AB  - OBJECT: Pituitary adenomas are very common neoplasms, constituting between 10 and
      20% of all primary brain tumors. Historically, the treatment armamentarium for
      pituitary adenomas has included medical management, microsurgery, and
      fractionated radiotherapy. More recently, radiosurgery has emerged as a viable
      treatment option. The goal of this research was to define more fully the
      efficacy, safety, and role of radiosurgery in the treatment of pituitary
      adenomas. METHODS: Medical literature databases were searched for articles
      pertaining to pituitary adenomas and stereotactic radiosurgery. Each study was
      examined to determine the number of patients, radiosurgical parameters (for
      example, maximal dose and tumor margin dose), duration of follow-up review, tumor
      growth control rate, complications, and rate of hormone normalization in the case
      of functioning adenomas. A total of 35 peer-reviewed studies involving 1621
      patients were examined. Radiosurgery resulted in the control of tumor size in
      approximately 90% of treated patients. The reported rates of hormone
      normalization for functioning adenomas varied substantially. This was due in part
      to widespread differences in endocrinological criteria used for the
      postradiosurgical assessment. The risks of hypopituitarism, radiation-induced
      neoplasia, and cerebral vasculopathy associated with radiosurgery appeared lower
      than those for fractionated radiation therapy. Nevertheless, further observation
      will be required to understand the true probabilities. The incidence of other
      serious complications following radiosurgery was quite low. CONCLUSIONS: Although
      microsurgery remains the primary treatment modality in most cases, stereotactic
      radiosurgery offers both safe and effective treatment for recurrent or residual
      pituitary adenomas. In rare instances, radiosurgery may be the best initial
      treatment for patients with pituitary adenomas. Further refinements in the
      radiosurgical technique will likely lead to improved outcomes.

PMID- 15871512
TI  - Intraoperative control of extracranial-intracranial bypass patency by near
      infrared indocyanine green videoangiography.
AB  - OBJECT: Recently, intraoperative fluorescence angiography in which indocyanine
      green (ICG) is used as a tracer has been introduced as a novel technique to
      confirm successful aneurysm clipping. The aim of the present study was to assess
      whether ICG videoangiography is also suitable for intraoperative confirmation of
      extracranial-intracranial bypass patency. METHODS: Forty patients undergoing
      cerebral revascularization for hemodynamic cerebral ischemia (11 patients), moya
      moya disease (18 patients), or complex intracranial aneurysms (11 patients) were
      included. Superficial temporal artery (STA)-middle cerebral artery (MCA) bypass
      surgery was performed 35 times in 30 patients (five patients with moyamoya
      underwent bilateral procedures), STA-posterior cerebral artery bypass surgery in
      two patients, and saphenous vein (SV) high-flow bypass surgery in eight patients.
      In each patient, following the completion of the anastomosis, ICG (0.3 mg/kg body
      weight) was given systemically via an intravenous bolus injection. A near
      infrared light emitted by laser diodes was used to illuminate the operating field
      and the intravascular fluorescence was recorded using an optical filter-equipped
      video camera. The findings of ICG videoangiography were compared with those of
      postoperative digital subtraction (DS) or computerized tomography (CT)
      angiography. In all cases excellent visualization of cerebral arteries, the
      bypass graft, and brain perfusion was noted. Indocyanine green videoangiography
      was used to identify four nonfunctioning STA-MCA bypasses, which could be revised
      successfully in all cases. In two cases of SV high-flow bypasses, ICG
      videoangiography revealed stenosis at the proximal anastomotic site, which was
      also revised successfully. In all cases the final findings of ICG
      videoangiography could be positively validated during the postoperative course by
      performing DS or CT angiography. CONCLUSIONS: Indocyanine green videoangiography
      provides a reliable and rapid intraoperative assessment of bypass patency. Thus,
      ICG videoangiography may help reduce the incidence of early bypass graft failure.

PMID- 15871513
TI  - Functional and phenotypic differences between glioblastoma multiforme-derived and
      normal human brain endothelial cells.
AB  - OBJECT: Glioblastomas multiforme (GBMs) are hypervascular tumors characterized by
      endothelial cell (EC) proliferation. There is increasing evidence that ECs that
      infiltrate systemic tumors are different from normal blood vessel cells; whether
      this difference is seen in the central nervous system between GBM and normal
      brain tissue is not known. The goal of this investigation was to characterize and
      compare the functional and phenotypic properties of GBM-associated ECs and normal
      brain ECs. METHODS: Human ECs were isolated from fresh tissue specimens, purified
      using flow cytometry, and characterized by immunostaining. Proliferation was
      measured by determining bromodeoxyuridine incorporation and Ki-67 staining, and
      by performing the monotetrazolium assay. The migration rate of the cells was
      determined using the modified Boyden chamber technique. Apoptosis was evaluated
      by performing the TUNEL assay, cell death enzyme-linked immunosorbent assay
      (ELISA), and annexin V staining. Growth factor production was analyzed using the
      ELISA technique. The brain tumor ECs differed from normal brain ECs
      morphologically and by their expression and distribution of specific markers
      (that is, vascular endothelial cadherin [VE-cadherin] and CD31). Functional
      differences between the two cell populations were also evident. The brain tumor
      ECs proliferated more slowly and underwent less apoptosis than normal brain ECs;
      however, the tumor ECs migrated faster than the normal ECs. The normal ECs were
      sensitive to growth factors such as vascular endothelial growth factor (VEGF) and
      endothelin-1 (ET-1), whereas the tumor ECs were not. In addition, the brain tumor
      ECs constitutively produced higher levels of ET-1 and VEGF, compared with the
      normal ECs. CONCLUSIONS: The data demonstrated that ECs derived from normal brain
      and from GBMs have significant phenotypic and functional distinctions. Further
      characterization of brain tumor ECs is essential for efficient antiangiogenic
      treatment of gliomas.

PMID- 15871514
TI  - Combined cimetidine and temozolomide, compared with temozolomide alone:
      significant increases in survival in nude mice bearing U373 human glioblastoma
      multiforme orthotopic xenografts.
AB  - OBJECT: Malignant gliomas consist of both heterogeneous proliferating and
      migrating cell subpopulations, with migrating glioma cells exhibiting less
      sensitivity to antiproliferative or proapoptotic drugs than proliferative cells.
      Therefore, the authors combined cimetidine, an antiinflammatory agent already
      proven to act against migrating epithelial cancer cells, with temozolomide to
      determine whether the combination induces antitumor activities in experimental
      orthotopic human gliomas compared with the effects of temozolomide alone.
      METHODS: Cimetidine added to temozolomide compared with temozolomide alone
      induced survival benefits in nude mice with U373 human glioblastoma multiforme
      (GBM) cells orthotopically xenografted in the brain. Computer-assisted phase
      contrast microscopy analyses of 9L rat and U373 human GBM cells showed that
      cimetidine significantly decreased the migration levels of these tumor cells in
      vitro at concentrations at which tumor growth levels were not modified (as
      revealed on monotetrazolium colorimetric assay). Computer-assisted microscope
      analyses of neoglycoconjugate-based glycohistochemical staining profiles of 9L
      gliosarcomas grown in vivo revealed that cimetidine significantly decreased
      expression levels of endogenous receptors for fucose and, to a lesser extent, for
      N-acetyl-lactosamine moieties. Endogenous receptors of this specificity are known
      to play important roles in adhesion and migration processes of brain tumor cells.
      CONCLUSIONS: Cimetidine, acting as an antiadhesive and therefore an antimigratory
      agent for glioma cells, could be added in complement to the cytotoxic
      temozolomide compound to combat both migrating and proliferating cells in GBM.

PMID- 15871515
TI  - Dexamethasone preventing contractile and cytoskeletal protein changes in the
      rabbit basilar artery after subarachnoid hemorrhage.
AB  - OBJECT: The aim of this project was to study the perturbations of four smooth
      muscle proteins and an extracellular protein, type I collagen, after subarachnoid
      hemorrhage (SAH) and to examine the possible preventive effects of dexamethasone.
      METHODS: Using a one-hemorrhage rabbit model, the authors first examined the
      effects of SAH on the expression of alpha-actin, h-caldesmon, vimentin,
      smoothelin-B, and type I collagen; second, they studied whether post-SAH systemic
      administration of dexamethasone (three daily injections) corrected the induced
      alterations. Measurements were obtained at Day 7 post-SAH. The proteins were
      studied by performing immunohistochemical staining and using a laser-scanning
      confocal microscope. Compared with control (sham-injured) arteries, the density
      of the media of arteries subjected to SAH was reduced for alpha-actin (-11%, p =
      0.01) and h-caldesmon (-15%, p = 0.06) but increased for vimentin (+15%, p =
      0.04) and smoothelin-B (+53%, p = 0.04). Among animals in which SAH was induced,
      arteries in those treated with dexamethasone demonstrated higher values of
      density for alpha-actin (+13%, p = 0.05) and h-caldesmon (+20%, p = 0.01), lower
      values for vimentin (-55%, p = 0.05), and nonsignificantly different values for
      smoothelin-B. The density of type I collagen in the adventitia decreased
      significantly after SAH (-45%, p = 0.01), but dexamethasone treatment had no
      effect on this decrease. CONCLUSIONS: The SAH-induced alterations in the density
      of three of four smooth-muscle proteins were prevented by dexamethasone
      treatment; two of these proteins--alpha-actin and h-caldesmon--are directly
      related to contraction. This drug may potentially be useful to prevent certain
      morphological and functional changes in cerebral arteries after SAH.

PMID- 15871516
TI  - Long-term high-frequency bilateral pallidal stimulation for neuroleptic-induced
      tardive dystonia. Report of two cases.
AB  - The authors report the results of long-term bilateral high-frequency pallidal
      stimulation in two patients affected by neuroleptic-induced dystonia. The first
      patient, a 33-year-old man, experienced a dystonic posture of the trunk, with
      involvement of the neck and upper and lower limbs after 11 years of treatment
      with neuroleptic drugs. The second patient, a 30-year-old man, presented with a
      torsion dystonia, spasmodic torticollis, and involuntary movements of the upper
      limbs, which appeared after 4 years of neuroleptic treatment. Both of these
      dystonias worsened even after the neuroleptic treatment had been discontinued,
      and neither patient responded to clozapine or benzodiazepine therapy. The time
      lapse between the first appearance of dystonia and surgery was, respectively, 5
      and 3 years. In each case bilateral stereotactic implantation of electrodes
      within the globus pallidus internus (GPI) was performed while the patient was in
      a state of general anesthesia. The electrodes were placed at the following
      anterior commissure-posterior commissure line-related coordinates: 20 mm lateral
      to the midline, 6 mm below the intercommissural plane, and 3 mm anterior to the
      midcommissural point. Electrical stimulation (130 Hz, 1 V, 90 microsec) was begun
      on the 1st postoperative day. In both patients, a genetic analysis positively
      ruled out a mutation in the DYT1 gene, and magnetic resonance imaging yielded
      normal findings in both cases. Extrapyramidal symptoms and dystonia disappeared
      almost completely and dramatically in both patients just a few days after high
      frequency bilateral pallidal stimulation commenced. Both patients regained
      autonomy and neuroleptic treatment was reinitiated. The follow-up period for both
      cases was 1 year. Long-term bilateral high-frequency stimulation of GPI resulted
      in a dramatic and long-lasting improvement of neuroleptic-induced tardive
      dystonia.

PMID- 15871517
TI  - De novo presentation of an arteriovenous malformation. Case report and review of
      the literature.
AB  - The authors report the case of a patient with a de novo arteriovenous
      malformation (AVM), indicating that the origin of these lesions may not always be
      congenital. A 3-year-old girl who was struck by a car suffered a mild head injury
      and experienced posttraumatic epilepsy. The initial magnetic resonance (MR) image
      obtained in this child revealed only a small contusion in the left frontal lobe.
      Intractable epilepsy subsequently developed. A second MR image obtained almost 4
      years after the injury demonstrated an AVM in the right posterior temporal lobe
      that was verified using angiography. The lesion was classified as a Spetzler
      Martin Grade III AVM. The patient underwent embolization of the feeding vessels
      followed by gamma knife surgery. Fourteen months after treatment she was
      asymptomatic. Follow-up MR images demonstrate no evidence of an AVM and no
      changes in the white matter. This case presents a de novo AVM that developed
      within approximately 4 years. The findings indicate that AVMs may not always be
      congenital and reinforce the concept that the natural history of AVMs is dynamic.
      Lesions may appear de novo, grow, and thrombose spontaneously.

PMID- 15871518
TI  - Intracranial metastasis from a sacrococcygeal chordoma. Case report.
AB  - Chordoma is a locally invasive tumor of low metastatic potential. Only six cases
      of chordoma that metastasized to the brain are found in the English literature.
      Most of these lesions were clinically silent and all were associated with
      extraneural metastases. The authors report a case of symptomatic brain metastasis
      from a sacrococcygeal chordoma in the absence of other metastases. The incidence,
      sites, and factors predictive of chordoma metastasis are discussed.

PMID- 15871519
TI  - Intraventricular chordoid meningioma presenting with Castleman disease due to
      overproduction of interleukin-6. Case report.
AB  - A rare case of chordoid meningioma in the lateral ventricle observed in an adult
      is reported. The first clinical manifestation of the disease was a prolonged
      fever of unknown origin. Abnormalities in the patient's blood chemistry,
      principally polyclonal hypergammaglobulinemia (immunoglobulin [Ig]G, IgA, and
      markedly IgE) and an elevated serum level of C-reactive protein, were associated
      with the disease. The tumor was histologically confirmed to be a chordoid
      meningioma, and its surgical removal resulted in complete resolution of the
      patient's symptoms. By combining reverse transcription-polymerase chain reaction
      and immunohistochemical analysis, it may be shown that cytokine production,
      including that of interleukin (IL)-6, IL-1beta, and vascular endothelial growth
      factor, plays a role in the pathogenesis of chordoid meningioma associated with
      Castleman syndrome.

PMID- 15871520
TI  - Malignant glioma-induced neuronal cell death in an organotypic glioma invasion
      model. Technical note.
AB  - Rapid growth and diffuse brain infiltration are hallmarks of malignant gliomas.
      The underlying molecular pathomechanisms of these tumors, however, remain to be
      determined. The authors present a novel glioma invasion model that allows
      researchers to monitor consecutively tumor cell proliferation and migration in an
      organotypic brain environment. Enhanced green fluorescent protein-labeled F98 rat
      glioma cells were implanted into slice cultures obtained from a rat hippocampus,
      and tumor growth was microscopically documented up to 20 days in vitro. Invasion
      along radially oriented migratory streams could be observed 5 days after
      implantation of rat F98, human U87MG, and mouse GL261 glioma cells, whereas human
      Be(2)c neuroblastoma cells and mouse HT22 hippocampal neurons failed to invade
      the brain parenchyma. Following implantation of F98 glioma cells into the
      entorhinal cortex, cell death was observed within the infiltrated brain
      parenchyma as well as in the neuroanatomically connected dentate gyrus.
      Application of the N-methyl-D-aspartate receptor antagonist MK801 to the culture
      medium significantly reduced neuronal degeneration in the dentate gyrus, whereas
      the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist
      GYKI 52466 inhibited peritumoral cytotoxicity. This new model allows researchers
      to address in a systematic manner the molecular pathways of brain invasion as
      well as specific tumor-host interactions such as necrosis.

PMID- 15871521
TI  - Battling blood loss in neurosurgery: Harvey Cushing's embrace of electrosurgery.
AB  - For his pioneering spirit, definitive work, and unparalleled devotion to
      conquering neurosurgery's toughest obstacles, Harvey Williams Cushing inarguably
      has earned the title, "The Father of Neurosurgery." His revolutionary
      incorporation of electrosurgical techniques in neurosurgery was not exceptional,
      but part of a pattern of recognizing, embracing, and establishing the use of
      medical technologies with great potential. Until 1910, Cushing had systematically
      reduced neurosurgery's primary complications--infection and the effects of
      intracranial pressure--to decrease mortality rates. Hemostasis had always been a
      concern of William Halsted's surgical protege, but only after 1910 could Cushing
      primarily focus on it. In fact, Cushing's crucial collaboration with William T.
      Bovie and his electrosurgical apparatus conquered this major obstacle in 1926.
      The nature of their collaboration--two experts in their respective fields who
      were passionate about their work, working side by side in the operating room-
      resulted in progress that surpassed all predecessors in the field. Cushing never
      did learn the physics behind one of the most important advances of his career.
      Nonetheless, he did know that by greatly reducing blood loss, electrosurgery
      allowed him to operate in patients whose tumors had been previously deemed
      inoperable and on the entire spectrum of neurosurgical patients more safely.

PMID- 15871522
TI  - Aprotinin and hemostasis.

PMID- 15871523
TI  - Trigeminal nerve.

PMID- 15871524
TI  - Effects of dissolved calcium and phosphorous on osteoblast responses.
AB  - The dissolution behavior of hydroxyapatite (HA) and its effect on the initial
      cellular response is of both fundamental and clinical importance. In this study,
      plasma-sprayed HA coatings were characterized by X-ray diffraction and Fourier
      transform infrared spectroscopy (FTIR). Calcium (Ca) and inorganic phosphorous
      (Pi) ions released from plasma-sprayed HA coatings within 3 weeks were measured
      by flame atomic absorption and colorimetrically molybdenum blue complex,
      respectively. To investigate the effect of dissolution of HA coatings on
      osteoblast response, additional Ca and Pi were added into the cell culture media
      to simulate the dissolution concentrations. Human embryonic palatal mesenchyme
      cells, an osteoblast precursor cell line, were used to evaluate the biological
      responses to enhanced Ca and Pi media over 2 weeks. Osteoblast differentiation
      and mineralization were measured by alkaline phosphatase-specific assay and 1,25
      (OH)2 vitamin D3 stimulated osteocalcin production. The coatings exhibited an HA
      type structure. FTIR indicated the possible presence of carbonates on the
      coatings. A dissolution study indicated a continual increase in Ca and Pi over
      time. In the cell culture study, enhanced osteoblast differentiation occurred in
      the presence of additional Ca concentration in the cell culture media. However,
      additional Pi concentration in the cell culture media was suggested to slow down
      osteoblast differentiation and mineralization.

PMID- 15871525
TI  - Dimensional stability of the alveolar ridge after implantation of a bioabsorbable
      bone graft substitute: a radiographic and histomorphometric study in rats.
AB  - This study evaluated reconstruction of the alveolar ridge after molar extraction
      in rats with bioabsorbable bone repair scaffolds. The material was prepared from
      the unsaturated polyester poly(propylene glycol-co-fumaric acid) (PPF), which may
      be cured in situ to form a porous scaffold. The intention is to use this material
      either as a stand-alone bone graft substitute or as an extender to autograft
      harvested from mandibular reconstruction sites. The bioactivity of the graft
      substitute was investigated in a rat residual ridge resorption model. PPF bone
      repair material was injected into the defect site, where it cross-linked in situ
      in the presence of a hydroxyapatite (HA) filler and effervescent agents. The PPF
      based material develops porosity during an in situ cure by generating carbon
      dioxide during the effervescent reaction of citric acid and sodium bicarbonate.
      The incorporation of HA promotes osteoconduction within the bone repair scaffold.
      In this study, bioactivity of the porous scaffold was evaluated as a function of
      HA particle size (micrometer-sized vs nanometer-sized particles). The maxillary
      or mandibular molars on the right side were extracted from 96 adult Sprague
      Dawley rats. A 2-mm round bur was used to create a uniform trench defect
      measuring 2 mm in diameter, 2 mm in depth, and 4 mm in length at each extraction
      site. The defect site was (1) treated with PPF bone repair material containing
      nanometer-sized HA, (2) treated with PPF material containing micrometer-sized HA,
      (3) treated with demineralized freeze-dried bone allograft, or (4) left
      untreated. Rats were sacrificed at 2, 4, 7, and 12 weeks postoperative.
      Resorption of the residual alveolar ridge was assessed by radiographic outcomes.
      Bone ingrowth through the defect site was measured by histomorphometric outcomes.
      Mandibular and maxillary ridge heights increased for all treatments used in this
      study. There were no clinical indications that addition of either of the PPF bone
      repair materials retarded hard- or soft-tissue healing of the extraction sites.
      Although not statistically significant, the mandibular defects treated with PPF
      containing nanometer-sized HA healed at a faster rate as determined by ridge
      height and new bone formation measurements when compared with the other
      treatments. These findings suggest the feasibility of using PPF bone graft
      substitutes for oral-maxillofacial applications.

PMID- 15871526
TI  - One-piece root-form implants: a return to simplicity.
AB  - Immediately loaded 1-piece dental implants were a standard treatment modality
      more than 30 years ago and, on occasion, resulted in excellent clinical
      successes. However, this technology also became associated with significant
      failure rates and fell out of favor. Since then, understanding of the site
      requirements and placement procedures necessary to ensure primary stability have
      advanced considerably. Implant designs and surface treatments also have evolved.
      In light of this greater understanding, a 1-piece root-form implant system has
      been developed. This article describes 4 clinical cases in which use of the new
      system was employed. In each case, the results included excellent stability,
      esthetics, and patient satisfaction.

PMID- 15871527
TI  - Antral membrane balloon elevation.
AB  - Many edentulous posterior maxilla are found to be encumbered by alveolar
      resorption and increased pneumatization of the sinus. These factors limit the
      quantity and quality of bone necessary for successful implant placement in these
      areas. One solution is to use shorter implants, but this often results in an
      unfavorable crown-root ratio. To create an improved environment in such regions,
      the classic sinus floor elevation with bone augmentation is a well-accepted
      technique. However, when the edentulous area is limited to a zone between 1 and 2
      teeth, lifting the membrane becomes difficult and may subject it to iatrogenic
      injury. The antral membrane balloon elevation technique, which is introduced in
      this preliminary report, is a modification of the currently used sinus lift. It
      elevates the membrane easily and makes the antral floor accessible for
      augmentation with grafting materials.

PMID- 15871528
TI  - Complete artificial dentition supported by endosseous implants: a case report of
      total in-office treatment.
AB  - This case report demonstrates the construction of a complete restoration of the
      dentition by the surgical placement of endosseous titanium implants that support
      a fixed prosthesis in each jaw. The positioning of the implants and teeth in the
      prostheses are important factors for a successful long-term result. Distribution
      of the occlusal biting forces over as many implants as possible is important. Off
      axial occlusal biting forces should be diverted to the anterior prostheses, where
      the forces are not as great and the posterior teeth are designed with flat
      occlusal surfaces that separate during excursionary chewing movements. Medial
      mandibular flexure caused by the contraction of the medial pterygoid muscle can
      be addressed by constructing the prosthesis in segments. This is so as not to
      have a rigid entity encased in flexing bone that may induce stress to the bone,
      leading to loss of implant integration and failure. Segmenting also insures an
      appropriate fit of the prosthesis with respect to casting and porcelain firing
      distortion. Lip support by means of a flange in the prosthesis may be necessary
      when there has been a large amount of bone loss from edentulous resorption.
      Cleaning and maintenance of the prostheses every 3 to 6 months is essential.

PMID- 15871529
TI  - A 24-year retrospective study of bone growth after implant placement.
AB  - This study quantifies the changes in bone height noted in the body of the
      edentulous mandibles when the load of the complete denture is born by an RA Ramus
      Frame Implant (Pacific Implant, Rio Dell, Calif). Eighty-three patients with
      implants were followed for 3 to 24 years. Pre- and postoperative panoramic films
      were taken and again at each succeeding 5-year follow-up. The results of the bone
      changes were gathered retrospectively and calculated. The data revealed a
      significant increase in bone height from 4.413 to 13 mm and statistically
      significant P values of <.0003 were determined. The growth of bone appears to be
      influenced by the design of the posterior feet, dominant chewing side, and a
      range of extreme atrophy from 5.9 mm to 15 mm. Also, the previously lost
      anatomical structures appear to repair, such as the luman of the mental foramen
      and the superior wall over the inferior alveolar canal. All mandibles were loaded
      postoperatively with an appliance having cutting bars and porcelain teeth or just
      porcelain teeth in both appliances.

PMID- 15871530
TI  - The legal doctrine of informed consent.

PMID- 15871532
TI  - The making of a nurse.

PMID- 15871531
TI  - Oral triazolam sedation in implant dentistry.

PMID- 15871533
TI  - Cardiovascular aspects of septic shock: pathophysiology, monitoring, and
      treatment.
AB  - The care of patients with septic shock is exceedingly complex. New therapies and
      monitoring technologies are being rapidly developed. To create an effective plan
      of care that integrates these new therapies and technologies, critical care
      nurses must understand the underlying pathophysiology of septic shock, techniques
      to accurately monitor patients' status, and the rationale for care.

PMID- 15871534
TI  - Indwelling Foley catheters: is the current design a source of erroneous
      measurement of urine output?

PMID- 15871535
TI  - Right-ventricular infarction.

PMID- 15871536
TI  - Regional use of complementary and alternative therapies by critical care nurses.

PMID- 15871537
TI  - Bold voices in progressive care: using shared decision making to implement
      evidence-based practice in progressive care.

PMID- 15871538
TI  - What is the proper activated clotting time (ACT) at which to remove a femoral
      sheath after PCI? What are the best "protocols" for sheath removal?

PMID- 15871539
TI  - What is the best way to document to prevent lawsuits?

PMID- 15871540
TI  - Beacon Bound: a journey toward excellence.

PMID- 15871541
TI  - Riding the wave of the future. Electronic patient charting debuts in student
      clinic.

PMID- 15871542
TI  - Muscle building: a scientific workout for Dr. Elisabeth Barton.
AB  - Dr. Elisabeth Barton spends her lab time building muscle. But no, you won't find
      her there lifting weights. This Assistant Professor of Anatomy and Cell Biology
      is working out the science of muscle repair. From the repair of muscles in the
      face to those in the limbs, Dr. Barton's research investigations are exploring
      the potential to help such diverse problems as temporomandibular dysfunction
      (TMD) and muscular dystrophy.

PMID- 15871543
TI  - Exploring the link. Periodontitis and preterm birth.

PMID- 15871544
TI  - What is the rationale for androgen therapy for women?
AB  - To date, no formal definition of female androgen insufficiency (FAI) based on
      strong epidemiological data exists. However the proposed key symptoms of FAI,
      being reduced libido, diminished well-being, and lowered mood, have been reported
      to respond well to testosterone replacement, generally without significant
      adverse effects. Androgens are quantitatively the predominant sex steroid in
      women, circulating in the micro- and nanomolar concentration range, compared with
      picomolar levels of estrogens. Androgens have important physiological roles in
      women, acting both as precursors for estrogen biosynthesis and directly via the
      androgen receptor. The most significant biologically active androgen is
      testosterone, which circulates bound tightly to sex hormone binding globulin and
      loosely to albumin. Circulating androgen levels decline in the years preceding
      menopause. This may be attributed to the gradual reduction in adrenal androgen
      production with age and to the loss of cyclical ovarian androgen production in
      the late reproductive years. Those who experience surgical menopause, have
      adrenal insufficiency or pituitary insufficiency, or those who experience
      premature ovarian failure, also have reduced androgen production. Androgen
      replacement therapy in the form of either dehydroepiandrosterone or testosterone
      is becoming increasingly widespread for the treatment of FAI. Evidence exists for
      the benefits of such therapy in relieving both the physical and psychological
      symptoms thought to be due to FAI in clinically affected women. However, clear
      guidelines regarding the diagnosis of androgen insufficiency, optimal therapeutic
      doses, and long-term safety remain lacking.

PMID- 15871545
TI  - Inflammation and its association with glucose disorders and cardiovascular
      disease.
AB  - This review article presents data to show that insulin resistance and diabetes
      mellitus are conditions associated with low-grade inflammation. It shows that
      inflammation pre-dates the detection of diabetes and predicts its occurrence.
      Furthermore, it discusses the inter-relationship between inflammation associated
      with insulin resistance and diabetes, and the inflammation associated with
      atherosclerosis, the main complication of insulin resistance and diabetes. These
      data provide a new paradigm for understanding how insulin resistance, diabetes,
      and cardiovascular disease are related to one another. This paradigm also has the
      potential for opening up new areas of research and treatment.

PMID- 15871546
TI  - Diabetic ketoacidosis: risk factors and management strategies.
AB  - Diabetic ketoacidosis (DKA) is the most common hyperglycemic emergency in
      patients with diabetes mellitus. DKA most often occurs in patients with type 1
      diabetes, but patients with type 2 diabetes are susceptible to DKA under
      stressful conditions, such as trauma, surgery, or infections. DKA is reported to
      be responsible for more than 100 000 hospital admissions per year in the US, and
      accounts for 4-9% of all hospital discharge summaries among patients with
      diabetes. Treatment of patients with DKA uses significant healthcare resources
      and accounts for 1 out of every 4 healthcare dollars spent on direct medical care
      for adult patients with type 1 diabetes in the US. Recent studies using
      standardized written guidelines for therapy have demonstrated a mortality rate of
      less than 5%, with higher mortality rates observed in elderly patients and those
      with concomitant life-threatening illnesses. Worldwide, infection is the most
      common precipitating cause for DKA, occurring in 30-50% of cases. Urinary tract
      infection and pneumonia account for the majority of infections. Other
      precipitating causes are intercurrent illnesses (i.e., surgery, trauma,
      myocardial ischemia, pancreatitis), psychological stress, and non-compliance with
      insulin therapy. The triad of uncontrolled hyperglycemia, metabolic acidosis and
      increased total body ketone concentration characterizes DKA. These metabolic
      derangements result from the combination of absolute or relative insulin
      deficiency and increased levels of counter-regulatory hormones (glucagon,
      catecholamines, cortisol, and growth hormone). Successful treatment of DKA
      requires frequent monitoring of patients, correction of hypovolemia and
      hyperglycemia, replacement of electrolyte losses, and careful search for the
      precipitating cause. Since the majority of DKA cases occur in patients with a
      known history of diabetes, this acute metabolic complication should be largely
      preventable through early detection, and by the education of patients, healthcare
      professionals, and the general public. The frequency of hospitalizations for DKA
      has been reduced following diabetes education programs, improved follow-up care,
      and access to medical advice. Novel approaches to patient education incorporating
      a variety of healthcare beliefs and socioeconomic issues are critical to an
      effective prevention program.

PMID- 15871547
TI  - Long-term efficacy and safety of somatropin for adult growth hormone deficiency.
AB  - The beneficial effects of somatropin (growth hormone [GH] replacement therapy) in
      adults are now established. Long-term somatropin administration in GH-deficient
      adults improves body composition, muscle strength, quality of life, bone mass and
      density, and lipoprotein pattern. The extent to which somatropin therapy can also
      reduce cardiovascular morbidity and mortality in GH-deficient adults remains to
      be determined. By starting with a low dose of somatropin, which is gradually
      increased based on clinical response (body composition, well-being, and serum
      insulin-like growth factor-1 concentration), effective treatment can be achieved
      with a minimum of fluid-related adverse effects. Thorough long-term monitoring of
      glucose metabolism, cardiovascular measurements, and underlying pituitary
      disease, is, however, mandatory.

PMID- 15871548
TI  - The costs of type 2 diabetes mellitus in Italy: a CODE-2 sub-study.
AB  - AIM: To estimate the direct, indirect, and intangible costs associated with type
      2 diabetes mellitus in Italy in 1998. To evaluate the economic impact of diabetic
      complications, and to investigate drug treatment patterns and associated costs in
      patients with type 2 diabetes. METHODS: The Italian arm of an international study
      (COsts of Diabetes in Europe--Type 2 [CODE-2], a descriptive, cross-sectional
      survey) was set up to collect information retrospectively by means of
      questionnaires from a sample of 1263 patients. Resource use was measured in
      monetary terms using a set of costs and tariffs. Intangible costs were estimated
      using the EuroQol questionnaire. RESULTS: The average yearly cost for medical
      resources for a patient with type 2 diabetes was 2991 Euro, whereas the estimated
      cost for the whole population with type 2 diabetes was about 5170 million Euro.
      This corresponds to 6.65% of the total healthcare expenditure (public and
      private) in Italy. Of direct costs, 29% was spent for the treatment of diabetes
      and 39% for the treatment of diabetic complications; while the remaining 32% was
      spent for healthcare not related to diabetes. Quality of life score in patients
      with type 2 diabetes (EuroQoL overall average score) was 0.68. CONCLUSIONS: Type
      2 diabetes has a high cost to society. The major cost component is due to the
      care of diabetic complications, not to the treatment of the illness itself; in
      particular, drug costs represent a relatively small proportion of such treatment
      cost.

PMID- 15871550
TI  - New modalities of transdermal testosterone replacement.
AB  - Hypogonadism, irrespective of its etiology, has a negative impact on various
      physiologic parameters. These parameters may improve with testosterone
      replacement therapy. Before 1990, intramuscular testosterone esters were the
      principal modality of testosterone replacement in men with hypogonadism. Although
      effective, they have a non-physiologic pharmacokinetic profile. Recently,
      transdermal preparations of testosterone have become widely available. These
      include a scrotal patch, non-scrotal patches and, the most recent development, a
      gel. Several studies have shown that transdermal testosterone replacement is
      physiologic, efficacious and has a good safety profile. Transdermal testosterone
      replacement improves bone mass and lean body mass, decreases fat mass, and
      improves mood and sexual function. There are no harmful effects on the prostate
      and lipids. Acne, polycythemia, and gynecomastia are less common with this form
      of therapy than with the intramuscular esters.

PMID- 15871551
TI  - Insulin pump therapy in childhood diabetes mellitus: guidelines for use.
AB  - The current goals for the therapy of children and adolescents with type 1
      diabetes mellitus are to achieve near-normal glycemia, minimize the risk of
      severe hypoglycemia, limit excessive weight gain while achieving adequate growth,
      improve quality of life for both the patients and their families, and delay or
      prevent vascular complications. Insulin pump therapy provides a treatment option
      that can significantly aid in achieving all of these goals across all age ranges
      of pediatric patients. Continuous subcutaneous insulin infusion (CSII) pump
      therapy can provide greater flexibility in the timing of meals and snacks, has
      programmable basal rates to optimize overnight glycemic control, can reduce the
      risk of exercise-induced hypoglycemia, and enhances the ability of the patient
      and the family members to achieve acceptable diabetes control. In pediatric
      patients, CSII has been shown to reduce both glycosylated hemoglobin levels and
      the frequency of severe hypoglycemia without increasing the risk of diabetic
      ketoacidosis. The effectiveness of CSII, improvements in pump technology, and the
      availability of very rapid-acting insulin analogs have fueled a dramatic increase
      in the use of this therapy. This review presents practical guidelines for the
      selection of patients, initiation of treatment and patient education, as well as
      guidelines for use while exercising and at school. Keys to the success of CSII
      are to have a multidisciplinary team of clinicians who are expert in the care of
      children with diabetes, and patients and families who are able to carry out the
      tasks of intensive treatment, including self-monitoring of blood glucose levels,
      carbohydrate counting, and infusion pump management. Patients and parents need to
      be able to recognize and treat hypoglycemia, and prevent the development of
      ketoacidosis. School personnel need to be involved in the treatment plan and
      individual algorithms developed for periods of extra exercise and activity. The
      recent introduction of methods for continuous glucose monitoring provides a new
      means to optimize the basal and bolus capabilities of CSII and offers hope for
      the development of a feedback-controlled artificial pancreas.

PMID- 15871552
TI  - Hyperprolactinemia: pathophysiology and management.
AB  - Hyperprolactinemia is commonly found in both female and male patients with
      abnormal sexual and/or reproductive function or with galactorrhea. If serum
      prolactin levels are above 200 microg/L, a prolactin-secreting pituitary adenoma
      (prolactinoma) is the underlying cause, but if levels are lower, differential
      diagnoses include the intake of various drugs, compression of the pituitary stalk
      by other pathology, hypothyroidism, renal failure, cirrhosis, chest wall lesions,
      or idiopathic hyperprolactinemia. When a pituitary tumor is present, patients
      often have pressure symptoms in addition to endocrine dysfunction, such as
      headaches, visual field defects, or cranial nerve deficits. The large majority of
      patients with prolactinomas, both micro- and macroprolactinomas, can be
      successfully treated with dopaminergic drugs as first-line treatment, with
      normalization of prolactin secretion and gonadal function, and with significant
      tumor shrinkage in a high percentage of cases. Surgical resection of the
      prolactinoma is the option for patients who may refuse or do not respond to long
      term pharmacological therapy. Radiotherapy and/or estrogens are also reasonable
      choices if surgery fails. In patients with asymptomatic microprolactinoma no
      treatment needs to be given and a regular follow-up with serial prolactin
      measurements and pituitary imaging should be organized. Currently, the most
      commonly used dopamine agonists are bromocriptine, pergolide, quinagolide and
      cabergoline. When comparing the plasma half-life, efficacy and tolerability of
      these drugs, cabergoline seems to have the most favorable profile, followed by
      quinagolide. Ifprolactin levels are well controlled with dopamine agonist
      therapy, gradual tapering of the dose to the lowest effective amount is
      recommended, and in a number of cases medication can be stopped after several
      years. Evidence to date suggests that cabergoline and quinagolide appear to have
      a good safety profile for women who wish to conceive, but hard evidence proving
      that dopamine agonists do not provoke congenital malformations when taken during
      early pregnancy is currently only available for bromocriptine. Once pregnant,
      dopamine agonist therapy should be immediately stopped, unless growth of a
      macroprolactinoma is likely or pressure symptoms occur. At our institution
      patients with symptomatic prolactinomas, both micro- and macroadenomas, are
      treated with cabergoline as the first-line aproach. In the small group of
      patients who do not respond to this treatment, or who refuse long-term therapy,
      surgery is offered. Radiotherapy is given if both pharmacologic therapy and
      surgery fail.

PMID- 15871553
TI  - Weight effect of current and experimental drugs for diabetes mellitus: from
      promotion to alleviation of obesity.
AB  - Two landmark intervention studies, the Diabetes Control and Complications Trial
      (DCCT) in patients with type 1 diabetes mellitus and the United Kingdom
      Prospective Diabetes Study (UKPDS) in patients with type 2 diabetes mellitus,
      have unequivocally demonstrated that intensive diabetes therapy reduces the risk
      of long-term diabetic complications. As a result, the commonly accepted treatment
      goal for most patients with diabetes is the achievement and maintenance of
      glycemic control that is as close to the normal range as safely possible.
      Important adverse effects of intensive diabetes therapy, particularly when the
      treatment includes insulin or several of the oral antihyperglycemic agents, are
      an increased risk of hypoglycemia and undesired weight gain. Improvement of
      glycemic control with insulin, insulin secretagogues (sulfonylureas,
      meglitinides), and insulin sensitizers (thiazolidinediones) is often accompanied
      by weight gain. The etiology of this weight gain is likely multifaceted,
      including a reduction of glucosuria, increased caloric intake to prevent
      hypoglycemia, and anabolic effects on adipose tissue. Biguanides and alpha
      glucosidase inhibitors have a neutral or even positive effect (decrease) on
      weight, which may partly be attributable to their non-insulinotropic mechanism of
      action, a modest effect on satiety, and to their gastrointestinal adverse effect
      profile. Several antihyperglycemic agents that are currently in clinical
      development may improve glycemic control in conjunction with weight reduction.
      These include an analog of the pancreatic beta-cell hormone amylin (pramlintide),
      as well as glucagon-like peptide-1 (GLP-1) and exendin, and their analogs.
      Pharmacological agents with antihyperglycemic and positive weight effects have
      the potential to become important additions to our therapeutic armamentarium, in
      that they may help to achieve glycemic targets while addressing the long-standing
      clinical problem of weight gain as an adverse effect of intensive diabetes
      therapy.

PMID- 15871554
TI  - Ethinylestradiol/drospirenone: a review of its use as an oral contraceptive.
AB  - Ethinylestradiol 30microg/drospirenone 3mg (Yasmin, petibelle) [EE/DRSP] is a
      combined contraceptive pill (CC) for the prevention of pregnancy in women of
      reproductive age. Drospirenone is a novel progestogen with antimineralocorticoid,
      progestogenic and antiandrogenic activity. The theoretical (0-0.07) and corrected
      (0.41-0.71) Pearl indices and pregnancy ratios (0.3-0.84) in young, healthy women
      aged 18-35 years (or 18-30 years if smokers) given 13-26 cycles of EE/DRSP in
      large multi-center trials indicate that this CC is highly effective in preventing
      pregnancy. EE/DRSP is equally as effective as ethinylestradiol
      30microg/desogestrel 150microg (EE/DSG; corrected Pearl index 0.28-0.41) in
      preventing pregnancy. EE/DRSP is generally well tolerated. The frequency and type
      of adverse event reported in clinical trials are typical of those observed with
      other CCs, and comparable to those in women receiving EE/DSG. The incidence of
      intermenstrual bleeding (spotting, breakthrough bleeding or both) during
      treatment with EE/DRSP in young, healthy women decreased rapidly after the first
      cycle to 9 to 18% in the second cycle and 6% after 26 cycles, indicating good
      cycle control. The incidence of intermenstrual bleeding was similar in recipients
      of EE/DSG (9 and 14% in cycle 2 and 10% in cycle 26). Bodyweight was maintained
      +/- 2kg in most young women who received EE/DRSP for up to 26 cycles. Neither
      EE/DRSP nor EE/DSG showed clinically significant effects on blood pressure.
      EE/DRSP improved premenstrual and menstrual symptoms (negative affect, water
      retention, increased appetite) compared with baseline in a noncomparative trial.
      A similar improvement in skin condition (acne, seborrhea) was observed in women
      receiving EE/DRSP or ethinylestradiol 35microg/cyproterone acetate 2mg in a
      randomized, double-blind trial. CONCLUSIONS: Data from several 1- to 2-year
      studies show that EE/DRSP is an effective oral contraceptive, with Pearl index
      values similar to those of established low-dose CCs. This combination is well
      tolerated, demonstrating good cycle control and a beneficial effect on skin
      condition and well-being (including some premenstrual and menstrual symptoms).
      EE/DRSP has demonstrated similar efficacy and tolerability to EE/DSG, but long
      term clinical experience is required to establish the position of EE/DRSP among
      other available CCs and to clarify any potential tolerability advantages.
      Nevertheless, because the management of tolerability is complicated by the
      idiosyncratic nature of the response of women to CCs containing different
      progestogens, EE/DRSP appears to be a useful treatment option for women desiring
      oral contraception.

PMID- 15871555
TI  - Spotlight on insulin aspart in type 1 and 2 diabetes mellitus.
AB  - Insulin aspart (NovoLog, NovoRapid), a rapid-acting human insulin analog,
      provides more rapid absorption than regular human insulin after subcutaneous
      administration. In most randomized, nonblind clinical trials in patients with
      type 1 diabetes mellitus, insulin aspart administered immediately before meals
      resulted in significantly lower mean glycosylated hemoglobin (HbA1c) levels than
      regular human insulin (usually administered 30 minutes before a meal). Insulin
      aspart also significantly improved postprandial glycemic control compared with
      regular human insulin. The efficacy of insulin aspart was similar to that of
      insulin lispro when administered to patients with type 1 diabetes mellitus via
      continuous subcutaneous infusion in a randomized, nonblind trial. Preliminary
      data from randomized, nonblind trials suggest insulin aspart had a trend towards
      lower HbA1c levels compared with regular human insulin in patients with type
      2,diabetes mellitus. Biphasic insulin aspart (30% soluble [rapid-acting] and 70%
      protamine-bound insulin aspart [BIAsp30]) [NovoLog Mix 70/30, NovoMix 30(2)]
      generally provided significantly better postprandial glucose control than a
      similar mixture of biphasic regular human insulin (BHI30) in a randomized,
      nonblind trial in patients with type 1 or 2 diabetes mellitus. However, the long
      term efficacy of BIAsp30 was similar to that of BHI30 after 2 years in a
      randomized, nonblind trial in patients with type 2 diabetes mellitus. Patients
      with type 1 or 2 diabetes mellitus reported greater treatment satisfaction with
      insulin aspart or BIAsp30 than with regular human insulin or BHI30. The overall
      incidence of hypoglycemia with insulin aspart was lower than, or similar to, that
      of regular human insulin. Moreover, insulin aspart tended to be associated with a
      lower occurrence of nocturnal hypoglycemia and severe hypoglycemic events than
      regular human insulin. CONCLUSION: The standard preparation of insulin aspart has
      the potential to better mimic the physiological response to meals than regular
      human insulin. Insulin aspart when combined with a suitable basal insulin
      improved overall glycemic control and led to a similar or lower number of
      hypoglycemic episodes compared with a similar regular human insulin regimen.
      Insulin aspart was generally as effective and well tolerated as insulin lispro
      when administered by continuous subcutaneous infusion in a single comparative
      trial. The efficacy of biphasic insulin aspart has been documented in a small
      number of trials. Both insulin aspart and biphasic insulin aspart provide for
      flexible and convenient administration. Insulin aspart is now well established as
      an effective and convenient means of providing glycemic control which offers
      clinical and practical advantages over regular human insulin.

PMID- 15871556
TI  - Rafts--the current picture.
AB  - Although evidences that cell membrane contains microdomains are accumulating, the
      exact properties, diversity and levels of organization of small lipid patches
      built mainly of cholesterol and sphingomyelin, termed rafts, remain to be
      elucidated. Our understanding of the cell membrane is increasing with each new
      raft feature discovered. Nowadays rafts are suggested to act as sites of cell
      signaling events, to be a part of protein sorting machinery but also they are
      used by several pathogens as gates into the cells. It is still unclear how rafts
      are connected to the membrane skeleton and cytoskeleton and with how many
      different types of rafts are we actually dealing with. This review summarizes
      some of the most recent discoveries trying to make a view of the complex raft
      properties.

PMID- 15871557
TI  - Capillary density and capillary-to-fibre ratio in vastus lateralis muscle of
      untrained and trained men.
AB  - Muscle fibre profile area (Af), volume density (Vv), capillary-to-fibre ratio
      (CF) and number of capillaries per fibre square millimetre (CD) were determined
      from needle biopsies of vastus lateralis of twenty-four male volunteers (mean +/-
      SD: age 25.4+/-5.8 years, height 178.6+/-5.5 cm, body mass 72.1+/-7.7 kg) of
      different training background. Seven subjects were untrained students (group A),
      nine were national and sub-national level endurance athletes (group B) with the
      background of 7.8+/-2.9 years of specialised training, and eight subjects were
      sprint-power athletes (group C) with 12.8+/-8.7 years of specialised training.
      Muscle biopsies of vastus lateralis were analysed histochemically for mATPase.
      Capillaries were visualized and counted using CD31 antibodies against endothelial
      cells. There were significant differences in the Vv of type I and type II muscle
      fibres in both trained groups, B (51.8%; 25.6%) and C (50.5%; 26.4%). However, in
      untrained group A that was treated as a reference group, the difference between
      Vv of type I and type II fibres was less prominent, nevertheless statistically
      significant (42.1%; 35.1%). There was also a significant difference in CF: 1.9 in
      group A and 2.1 in groups B and C. The number of capillaries per mm2 (CD) was 245
      (group A), 308 (group B) and 325 (group C). Significant differences (P<0.05) in
      CF and CD, were found only between group A (1.9; 245) and both groups of trained
      men, B and C (2.1; 308 and 325). However, endurance athletes (group B), such as
      long-distance runners, cyclists and cross country skiers, did not differ from the
      athletes representing short term, high power output sports (group C) such as ice
      hockey, karate, ski-jumping, volleyball, soccer and modern dance.

PMID- 15871558
TI  - Modification of immunocytochemical ZAP-70 assay for potential clinical
      application in B-cell chronic lymphocytic leukemia.
AB  - The ZAP-70 protein is a member of the Syk/ZAP protein tyrosine kinase family,
      normally expressed in T cells and NK cells but not found in normal, mature B
      cells. The protein plays a critical role in the initiation of T-cell signaling.
      Leukemic cells from patients with B-cell chronic lymphocytic leukemia (B-CLL)
      that expressed nonmutated immunoglobulin V genes were found to express levels of
      ZAP-70 protein that were comparable to those detected in T cells of healthy
      adults. The ZAP-70 protein expression can be evaluated by flow cytometry and may
      be used as a prognostic marker in B-CLL patients. We modified the method of
      immunocytochemical assessment of ZAP-70 expression. The traditional two-step
      method with monoclonal anti-ZAP-70 antibody in the first step followed by FITC
      conjugated goat anti-mouse IgG was changed for one-step method with monoclonal
      anti-ZAP-70 antibody labeled by Zenon Alexa Fluor 488. The method is simple and
      fast. The major advantage of Zenon labeling technique is its compatibility with
      simultaneous staining of surface antigens. The cells may be earlier immunostained
      for CD3, CD19 and/or CD5 to compare of the ZAP-70 kinase expression in B and T
      cells.

PMID- 15871559
TI  - Generation of dendritic cells from human peripheral blood monocytes--comparison
      of different culture media.
AB  - Culture medium or medium supplement is one of the factors responsible for
      dendritic cell (DC) generation, but little is known about the influence of
      various media on DC culture. In our study we generated DC from adherent monocytes
      of human peripheral blood in the presence of GM-CSF, IL-4 and TNF-alpha. The
      following culture media were used: RPMI 1640 supplemented with 2% human serum
      albumin; RPMI 1640 supplemented with 2% TCH serum replacement; X-VIVO 15 and
      Panserin 501. Flow cytometry analysis revealed that in all media cells were CD83+
      and lost CD14. Interestingly, the use of Panserin and RPMI with albumin
      preferentially gave rise to CD1a+ DC, whereas in X-VIVO and RPMI with TCH we
      observed both CD1a+ and CD1a-. Our results showed that RPMI with TCH yielded the
      highest percentage of cells expressing both CD80 and CD86 molecules and, in
      contrast to other media, the higher percentage of CD86+ cells in comparison to
      CD80+ cells.

PMID- 15871560
TI  - Prognostic evaluation of CD44 expression in correlation with bcl-2 and p53 in
      colorectal cancer.
AB  - To investigate the expression of CD44 in colorectal cancer and examine its
      association with clinicopathological features, bcl-2, p53 and long-term outcome,
      paraffin-embedded tumour specimens from 61 patients with Dukes stage B (AJCC/UICC
      stage I) and 39 patients with Dukes stage C (AJCC/UICC stage III) colorectal
      adenocarcinoma were assessed by immunohistochemistry. The expression of CD44, bcl
      2 and p53 were correlated with 5-year follow-up. Low CD44 expression was present
      in 30%, moderate in 30% and extensive in 40% of cases. It was not related to
      patient sex and age but was related to tumour differentiation, stage and tumour
      site. No association was demonstrated between CD44 and bcl-2. However, there was
      significant evidence of an association between CD44 and p53 in 66 cases in which
      p53 was previously assessed. There was a trend towards increased survival in
      patients whose tumours expressed lower levels of CD44 protein. When entered into
      multivariate analysis model, which also included bcl-2 and p53, CD44 staining
      emerged as an indicator of poor prognosis in colorectal cancer patients.

PMID- 15871561
TI  - Modulation of testicular macrophage activity by collagenase.
AB  - Testicular macrophages (TMs) are located in the interstitial tissue of male
      gonad. These phagocytic cells take part in forming the organ-specific functional
      blood-testis barrier and participate in the regulation of the local hormonal
      balance. In the present study, we isolated TMs from testicular tissues using
      previously described methods--mechanical (M-TMs) or enzymatic, by treatment with
      collagenase (E-TMs) and then we studied production by these cells of several
      cytokines and reactive oxygen intermediates (ROI's). Similarly treated oil
      induced peritoneal macrophages (PMs) were used as control cells. PMs had a higher
      baseline level of production of TNF-alpha, IL-6, IL-10 and IL-12 than M-TMs and
      collagenase treatment increased the production of these cytokines (except IL-12)
      by both cell populations. This effect was significantly more expressed in TMs. In
      contrast to PMs, TMs produced little ROI's when stimulated by zymosan. We
      conclude that in the case of local inflammation in the testis, ROI-negative TMs
      do not contribute to the tissue damage and instead may direct the local immune
      response into humoral pathway.

PMID- 15871562
TI  - Atresia of large ovarian follicles of the rat.
AB  - In the rat, at the beginning of pregnancy a cohort of antral follicles develops
      until the preovulatory stage. However, these follicles, differentiating in the
      hyperprolactinemic milieu, produce only small amount of estradiol, do not ovulate
      and undergo rapid degeneration. They constitute an interesting physiological
      model of atresia. In the present study, we analysed the development and
      subsequent degeneration of such follicles. The study was performed on Wistar
      female rats killed in succession between days 1-9 of pregnancy. Excised ovaries
      were submitted to a routine histological procedure. Paraffin sections were
      subjected to hematoxylin and eosin staining or in situ DNA labelling.
      Histological and TUNEL staining revealed that the investigated group of follicles
      grew slower than that on the corresponding days of the estrous cycle and reached
      a preovulatory size and morphological appearance on day 5 of pregnancy. They did
      not ovulate and between days 6 and 9 of pregnancy an increasing number of
      apoptotic cells appeared within these follicles. They were localized
      predominantly in the antral granulosa layer, especially near the cumulus oophorus
      complex (COC) and in the region linking the COC with the follicular wall. The COC
      and the theca layer were much less affected. In late stages of atresia, also
      cumulus cells became apoptotic but degenerating oocytes did not exhibit positive
      TUNEL staining. Only limited number of the theca cells have undergone apoptosis
      and generally they were not hypertrophied. Our findings indicate that much
      smaller than normal amount of intrafollicular estradiol was sufficient to support
      a normal, according to the morphological criteria, although slower development of
      antral follicles to the late preovulatory stage.

PMID- 15871563
TI  - Morphological, histochemical and immunohistochemical study of the gill epithelium
      in the abyssal teleost fish Coelorhynchus coelorhynchus.
AB  - Histochemical and immunohistochemical study was carried out on nitrinergic
      innervation and neuroendocrine system in the gill epithelium of the abyssal fish
      Coelorhynchus coelorhynchus. The results showed that nNOS-positive nerve fibers,
      originating from the branchial arch were present in the subepithelial tissue of
      branchial primary filament. nNOS-positive neuroendocrine cells were also present
      in the primary filaments and secondary lamellae. Numerous mucous cells in the
      gill epithelium were AB/PAS-positive, while sialic acid was absent as confirmed
      by neuraminidase reaction and WGA lectin histochemistry. The mucus compounds in
      abyssal teleost fish are different from those found in pelagic species, being
      related to their living conditions. In abyssal species, greater numbers of
      chloride and neuroendocrine cells are involved in the movement of water and
      electrolytes. Neuroendocrine cells possess oxygen receptors which mediate the
      cardiovascular and ventilatory response to oxygen deficiency, as reported in
      teleost species. Besides, NO contributes through nervous stimulation to the
      regulation of vascular tone and blood circulation in the gill.

PMID- 15871564
TI  - Stereological analysis of mitochondria in embryos of Rana temporaria and Bufo
      bufo during cleavage.
AB  - Total numbers of mitochondria and their morphology have been quantitatively
      determined in mature oocytes and in cleaving embryos of two anuran species Rana
      temporaria and Bufo bufo using stereological methods. Surface densities of inner
      mitochondrial membranes for both studied species during cleavage ranged from 5.43
      m2/cm3 to 7.53 m2/cm3, whereas volume densities of mitochondria did not exceed
      1.65%. Since values of these parameters were low, thus embryos during cleavage
      may be considered as metabolically "silent". Transition of ultrastructural
      morphology of mitochondria towards that characterising actively respiring
      organelles occurs at stage 9 for R. temporaria and at stage 8 for B. bufo,
      correlated with blastula-gastrula and mid-blastula transition, respectively. The
      total numbers of mitochondria N(c) in mature oocytes are as high as 114.8 and
      107.2 millions for R. temporaria and B. bufo, respectively, and during cleavage
      at late blastula stages they increase to 300 millions for both species under
      study. We suggest that an undefined mechanism might eliminate during cleavage
      those amphibian embryos which contain small number of mitochondria and low levels
      of nutrient substances.

PMID- 15871565
TI  - GA3 content in young and mature antheridia of Chara tomentosa estimated by
      capillary electrophoresis.
AB  - The content of gibberellic acid (GA3) in male sex organs of Chara tomentosa L.
      was estimated using capillary electrophoresis. Young antheridia contained 0.25
      microg GA3 while mature ones 0.48 microg per antheridium. Although there are
      significant differences in GA3 content in antheridia between C. vulgaris and C.
      tomentosa, these values calculated per one spermatid are 2.4 and 3.3 pg,
      respectively. The present results compiled with the previous knowledge about
      regulation of GA3-dependent development of Characeae species allow an implication
      that the mechanisms controlling antheridia differentiation in both species can be
      similar.

PMID- 15871566
TI  - Ring vaccination versus mass vaccination in event of a smallpox attack.
AB  - Since vaccination is critical in responding to smallpox exposure, vaccination
      strategies must be evaluated during bioterrorism preparedness. Information on
      historical factors, smallpox characteristics, public health capabilities and
      hypothetical attack scenarios was used to evaluate major vaccination strategies.
      In event of a smallpox attack, the optimal strategy is situational, mass
      vaccination may be best for dense island populations such as Oahu.

PMID- 15871567
TI  - Descriptive epidemiology of congenital hydrocephaly in Hawaii, 1986--2000.
AB  - Using data from a birth defects registry, this study examined the epidemiology of
      hydrocephaly in Hawaii during 1986--2000. There were 294 cases of hydrocephaly,
      resulting in a rate of 10.4 per 10,000 live births. The hydrocephaly rate was
      lower with increased maternal age and female sex and higher with lower birth
      weight, lower gestational age, and multiple gestation pregnancy.

PMID- 15871568
TI  - Normal oxygen saturation values in pediatric patients.
AB  - OBJECTIVES: To determine normal oxygen saturation (OSAT) values in infants and
      children measured by pulse oximetry METHODS: Infants and children admitted to a
      children's hospital for elective surgery from 11/20/2000 to 3/30/2002 underwent
      surgical clearance screens consisting of illness symptoms, vital signs and OSAT
      in room air Based on the presence of respiratory infection (RI) symptoms, a
      "normal" patient was defined as one without respiratory symptoms and who was not
      scheduled for surgery involving the airway pulmonary or cardiovascular systems
      (APC). RESULTS: Of the 3600 forms collected, 2069 were completely filled out and
      for elective surgery. For all age groups combined, the percent of patients
      undergoing APC surgery or with RI symptoms for each OSAT were as follows (OSAT:
      %patients APC/RI): 100%: 13%, 99%-99.5%: 15%, 98%-98.5%: 14%, 97%-97.5%: 18%, 96%
      96.5%: 38%, 95%-95.5%: 29%, and <95%: 0%. CONCLUSIONS: Although OSAT of 95% and
      96% are adequate (i.e., not requiring acute oxygen therapy), these values are
      associated with higher rates of APC/RI involvement and thus should be considered
      potentially abnormal. OSAT of 97% is on the border of normal. Normal OSATs can
      occur with APC/RI conditions, but an OSAT less than 97% is associated with a
      higher risk of an APC/RI condition.

PMID- 15871569
TI  - Using the world wide web to facilitate the editing and publishing of a textbook
      for faculty professional development.
AB  - OBJECTIVE: The purpose of this report is to describe the editing and publication
      of a textbook to increase the opportunity for faculty to contribute textbook
      chapters, using the internet WWW to facilitate the editing process. METHODOLOGY:
      An outline of 22 sections containing 214 chapters, was developed. Each section
      was assigned to an editor Editors recruited authors for each of their section
      chapters. Chapters were submitted to the editors, then a chief editor completed
      the editing for the chapter. RESULTS: Chapters that were completed early were
      posted on the WWW which permitted additional review by the authors facilitating
      communication with the editors. The additional lead time on the WWW permitted
      indexing and identification by internet search engines (e.g., Google), so that by
      the time the textbook was completed, most major search engines had already
      identified the on-line textbook. Page/type-setting was streamlined by the
      electronic transfer of the equivalent on-line chapter files to the publisher. 41
      chapters were contributed by 18 senior faculty, 51 chapters were contributed by
      29 assistant professors, 46 chapters were contributed by 23 non-faculty community
      physicians, 38 chapters were contributed by 27 residents, and 40 chapters were
      contributed by 37 medical students. CONCLUSION: A textbook project such as this
      provides faculty with the opportunity to contribute to the medical literature
      enhancing their professional development. The WWW provides a new forum for
      publishing a textbook. It also provides a new communication option between
      editors and authors to better coordinate the content and editorial style of the
      chapters.

PMID- 15871570
TI  - Leadership training in maternal and child health.

PMID- 15871571
TI  - The two faces of telomerase.

PMID- 15871572
TI  - World Voice Day.

PMID- 15871573
TI  - External auditory canal polyp.

PMID- 15871574
TI  - Endoscopic view of sphenoid fungal sinusitis.

PMID- 15871575
TI  - Subglottic synechia.

PMID- 15871576
TI  - Giant antrochoanal polyp: MRI findings.

PMID- 15871577
TI  - Canalicular adenoma.

PMID- 15871578
TI  - Nonpulsatile carotid body tumor in a teenager.

PMID- 15871579
TI  - Endonasal placement of spreader grafts in rhinoplasty.

PMID- 15871580
TI  - Evidence-based practice management.

PMID- 15871582
TI  - Olfactory neuroblastoma: a case report and review of the literature.
AB  - Malignant tumors of the nasal cavity are rare. We report the case of an elderly
      woman who consulted us with a 4-year history of progressive nasal obstruction,
      occasional epistaxis, facial pain, and watering of the eyes. A diagnosis of
      olfactory neuroblastoma was established by histopathology and confirmed by
      immunohistochemistry. On staging, the mass was classified as a Kadish stage B
      tumor. The mass was excised via a lateral rhinotomy approach, and the tumor was
      peeled away completely from the cribriform plate with endoscopes. The patient
      underwent postoperative radiation, and she was free of recurrence at follow-up 15
      months later.

PMID- 15871581
TI  - Surgical-handling properties of the titanium prosthesis in ossiculoplasty.
AB  - Despite the wide variety of ossiculoplasty techniques that are available, success
      rates are limited. Current use indicates that surgeons prefer ceramic, autograft
      bone, and plastic pore prostheses. During the past decade, titanium prostheses
      have been used with great promise. Although their use is not widespread,
      satisfaction rates are high. An earlier study of ossiculoplasty showed that
      titanium prostheses were effective in reducing conductive hearing loss. To date,
      the surgical-handling attributes of titanium middle ear prostheses have not been
      assessed. We report the results of our survey of 32 otologic surgeons who used
      the open Tubingen titanium prosthesis for primary and revision ossiculoplasty
      during tympanoplasty in 400 patients at 12 academic and nonacademic
      otolaryngology clinics, most of them in Germany. Because the audiometric efficacy
      of titanium prostheses has been previously reported, our primary outcomes
      measures included ease of use with respect to the amount of time required to
      prepare the implants for placement and the surgeons' overall impression of the
      intraoperative handling characteristics of the implants, taking into
      consideration factors such as positioning, length adjustment, visibility, and the
      stability of the coupling. Surgeons also compared the properties of the titanium
      implant with those of gold, ceramic, and autograft implants that they had used in
      the past. Based on the results of 383 of the 400 ossiculoplasties, our survey
      revealed that the titanium implant was significantly superior to the others in
      all measured respects.

PMID- 15871583
TI  - Preoperative computerized dynamic posturography as a prognostic indicator of
      balance function in patients with acoustic neuroma.
AB  - We conducted a study to determine the prognostic reliability of preoperative
      computerized dynamic posturography (CDP) in patients undergoing surgical excision
      of an acoustic neuroma. Our goal was to determine the correlation between
      objective preoperative assessments of balance function and subjective
      postoperative patient self-assessments. To that end, we retrospectively reviewed
      the records of 21 adults who had undergone preoperative CDP, and we subsequently
      obtained their subjective assessments of balance function by follow-up telephone
      surveys at least 1 year postoperatively. We conclude that although CDP has proven
      to be useful in many aspects of balance evaluation, it did not appear to be a
      valuable predictor of subjective postoperative balance function in these
      patients.

PMID- 15871584
TI  - Nasopharyngeal carcinoma with axillary node involvement as a component of failure
      following chemoradiotherapy.
AB  - We describe the treatment course and imaging correlations in a patient with a
      unique case of undifferentiated nasopharyngeal carcinoma with axillary lymph node
      involvement as a component of failure following chemoradiotherapy. To our
      knowledge, this is the only such case reported in the literature. A preliminary
      diagnosis ofaxillary node involvement was based on both positron-emission
      tomography and computed tomography; these findings were subsequently confirmed by
      pathologic review following dissection of the node. This case represents a rare
      presentation of a recurrent nasopharyngeal carcinoma and illustrates the
      importance of a comprehensive physical examination and correlation with imaging
      modalities when following these patients over time.

PMID- 15871585
TI  - Pediatric allergic rhinitis: factors affecting treatment choice.
AB  - Allergic rhinitis is the mostprevalent chronic allergic disease in children.
      Although it is not life-threatening, it can have a significantly detrimental
      effect on a childs quality of life, and it may exacerbate a number of common
      comorbidities, including asthma and sinusitis. The Allergic Rhinitis and its
      Impact on Asthma guidelines, an evidence-based algorithm for the treatment of
      allergic rhinitis, advocate the use of antihistamines for the treatment of the
      broad spectrum of the disease. However, first-generation antihistamines are
      associated with a number of adverse events, including central nervous system
      impairment and anticholinergic and cardiovascular effects. Moreover, these agents
      have not been rigorously tested in the pediatric population. Nevertheless, first
      generation antihistamines remain the most frequently prescribed agents in this
      class of drugs. This is despite the fact that the second-generation
      antihistamines are largely free of the undesirable side effects associated with
      their predecessors and the fact that they have been shown to be effective in
      relieving allergic rhinitis symptoms in children in a number of large-scale
      clinical trials. Therefore, when selecting an antihistamine for a child, it would
      be prudent to consider the full range of antihistamines and to base the selection
      of a particular drug on its efficacy, onset and duration of action, and safety
      profile.

PMID- 15871586
TI  - Da Vinci robot-assisted excision of a vallecular cyst: a case report.
AB  - The da Vinci Surgical System is a new and exciting entrant into the field of
      robotic technology. This system is undergoing considerable research and is being
      practically applied in general surgery, cardiothoracic surgery, urology, and
      gynecology. We have previously described our experience with the da Vinci system
      in the laboratory setting, and we have reviewed its potential applications in
      otolaryngology. Here we present a case report of the first da Vinci-assisted
      excision of a vallecular cyst in a human. Although we initially encountered some
      difficulties in the setup, we were able to perform the procedure with moderate
      ease and without complication. The potential of the da Vinci system in
      otolaryngology is promising. Further research is needed to explore all of its
      possible uses in our field.

PMID- 15871587
TI  - Sternocleidomastoid muscle flap reconstruction during parotidectomy to prevent
      Frey's syndrome and facial contour deformity.
AB  - We studied the incidence of Frey's syndrome and facial contour deformity in two
      groups of patients who had undergone superficial parotidectomy. One group was
      made up of 12 patients who were randomized to undergo reconstruction of the
      surgical defect with a sternocleidomastoid muscle flap; the other 12 patients did
      not receive a flap. All 24 patients were evaluated via a short questionnaire, the
      starch-iodine test, and a visual examination. On the questionnaire, none of the
      24 patients said they experienced abnormal facial sweating, flushing, or warmth
      while eating, although 6 of the 12 patients in the nonflap group had a mildly
      positive starch-iodine test. No patient in the flap group had a positive test.
      The difference between the two groups was statistically significant (p < 0.05).
      No statistically significant difference was seen between the two groups with
      respect to cosmetic results.

PMID- 15871588
TI  - Assessing a patient's spiritual needs: a comprehensive instrument.
AB  - Seven major constructs-belonging, meaning, hope, the sacred, morality, beauty,
      and acceptance of dying-were revealed in an analysis of the literature pertaining
      to patient spiritual needs. The authors embedded these constructs within a 29
      item survey designed to be inclusive of traditional religion, as well as non
      institutional-based spirituality. This article describes the development of a
      multidimensional instrument designed to assess a patient's spiritual needs. This
      framework for understanding a patient's spiritual needs hopefully contributes to
      the growing body of literature, providing direction to healthcare professionals
      interested in a more holistic approach to patient well-being.

PMID- 15871589
TI  - Effective anxiety treatment prior to diagnostic cardiac catheterization.
AB  - Music therapy, massage, guided imagery, therapeutic touch, and stress management
      instruction have been used successfully to decrease patient anxiety prior to
      diagnostic cardiac catheterization, providing better patient outcomes. The
      anxiety experienced among patients may have various causes, including not feeling
      cared about as an individual, too much waiting time before the procedure begins,
      and physical discomfort. This review determines nursing interventions that may
      effectively reduce anxiety prior to diagnostic cardiac catheterization.

PMID- 15871590
TI  - Improving healthcare delivery with the transformational whole person care model.
AB  - A Whole Person Care model was developed by The New England School of Whole Health
      Education following a 2-year pilot study that demonstrated the transformational
      effects of whole health education. This holistic model of health education and
      behavioral interaction provides a tool for nurses, physicians, and staff to
      redirect the momentum of care toward in-the-moment, relationship-centered whole
      person care, improving healthcare worker and patient satisfaction and outcomes.

PMID- 15871591
TI  - The effects of mindfulness-based stress reduction on nurse stress and burnout: a
      qualitative and quantitative study, part III.
AB  - Part III of the study on mindfulness-based stress reduction (MBSR) describes
      qualitative data and discusses the implications of the findings. Study analysis
      revealed that nurses found MBSR helpful. Greater relaxation and self-care and
      improvement in work and family relationships were among reported benefits.
      Challenges included restlessness, physical pain, and dealing with difficult
      emotions.

PMID- 15871592
TI  - The role of diversional activities in the general medical hospital setting.
AB  - Many patients go through traumatic experiences in response to surgery, illness,
      or prolonged hospitalizations. The medicines and anesthesia they are introduced
      to, as well as metabolic changes and withdrawal from substances, often cause
      negative effects on their psyche. Some of these effects take the form of
      depression, psychosis, or delirium. Additionally, patients with preexisting
      dementia are often exacerbated by the hospitalization, causing increased
      confusion and agitation. Although generally reversible, it is important for
      healthcare practitioners to explore nonpharmacologic alternatives and reexamine
      the power of milieu therapy in the general medical setting.

PMID- 15871593
TI  - Chakra talk: exploring human energy systems.

PMID- 15871594
TI  - Foreshortened dorsal extension of the central sulcus in Williams syndrome.
AB  - Williams syndrome (WMS) is a genetic condition resulting from a hemideletion on
      chromosome 7 that causes cognitive impairment, and a variety of growth and
      physical abnormalities. Little is currently known about brain morphology in WMS,
      although one recent MRI report suggested that the central sulcus was abnormally
      short on its dorsal end compared to normal IQ controls. We sought to replicate
      this finding in a group of 28 persons with WMS in comparison to both an age and
      sex matched normal IQ control group (n = 22). In addition, we sought to test the
      specificity of this finding by a further comparison to an IQ matched control
      group (n = 20). Using high resolution isotropic voxel MRI, the dorsal and ventral
      extension of the central sulcus was traced and the distance from the
      interhemispheric and sylvian fissures was measured. The dorsal extension of the
      central sulcus in both hemispheres was significantly more distant from the
      interhemispheric fissure in WMS compared to the lower IQ group and to the normal
      control group (p's < 0.001). There was no significant difference between groups
      in the ventral end of the central sulcus. These results suggest that the abnormal
      dorsal end of the central sulcus may be a specific characteristic of WMS not
      shared with general mental retardation or low IQ.

PMID- 15871595
TI  - Brain event-related potentials (ERPs) measured at birth predict later language
      development in children with and without familial risk for dyslexia.
AB  - We report associations between brain event-related potentials (ERPs) measured
      from newborns with and without familial risk for dyslexia and these same
      children's later language and verbal memory skills at 2.5, 3.5, and 5 years of
      age. ERPs to synthetic consonant-vowel syllables (/ba/, /da/, /ga/; presented
      equiprobably with 3,910-7,285 msec interstimulus intervals) were recorded from 26
      newborns at risk for familial dyslexia and 23 control infants participating in
      the Jyvaskyla Longitudinal Study of Dyslexia. The correlation and regression
      analyses showed that the at-risk type of response pattern at birth (a slower
      shift in polarity from positivity to negativity in responses to /ga/ at 540-630
      msec) in the right hemisphere was related to significantly poorer receptive
      language skills across both groups at the age of 2.5 years. The similar ERP
      pattern in the left hemisphere was associated with poorer verbal memory skills at
      the age of 5 years. These results demonstrate that ERPs of newborns may be valid
      predictors of later language and neurocognitive outcomes.

PMID- 15871596
TI  - Anatomical signatures of dyslexia in children: unique information from manual and
      voxel based morphometry brain measures.
AB  - Thirteen male control and thirteen male dyslexic children (age, 121-152 months)
      were studied to determine if voxel based morphometry (VBM) could identify
      anatomical differences in the right cerebellar anterior lobe, and right and left
      pars triangularis that were identified with manual measures of the same children.
      VBM demonstrated significant gray and white matter differences in these three
      brain regions. In contrast to the manual results, these differences were not
      significant after controlling for brain volume, suggesting the manual measures
      captured additional important variance that distinguished the groups. Post-hoc
      VBM comparisons demonstrated white matter volume differences in a left temporal
      parietal region that are consistent in location with results from diffusion
      tensor imaging studies of dyslexia. The VBM analyses also identified, gray matter
      volume differences in the left and right lingual gyrus, left inferior parietal
      lobule and cerebellum, areas that had not been examined with manual methods. We
      conclude that manual and automated methods provide valuable and complementary
      approaches to the search for functionally significant neurobiological
      characteristics of dyslexia.

PMID- 15871597
TI  - SPECT findings in children with specific language impairment.
AB  - Findings from 99mTc-HMPAO SPECT measurements at rest in a group of 19 school-age
      children with specific language impairment (SLI) were compared to a group of 12
      children with attention-deficit hyperactivity disorder (ADHD). The regional
      cerebral blood flow (CBF) distributions were different in the two groups.
      Children with SLI showed significantly lower CBF values in the right parietal
      region and in the subcortical region compared to the ADHD group. In addition, the
      SLI group had symmetric CBF distributions in the left and right temporal regions,
      whereas the ADHD group showed the usual asymmetry with left-sided hemispheric
      predominance in the temporal regions. The findings give further evidence for
      anomalous neurodevelopment with deviant hemispheric lateralization as an
      important factor in the aetiology of SLI. They also point to the role of
      subcortical structures in language impairment in childhood. Earlier focus on
      cortical structures in SLI research needs to be widened to include subcortical
      regions as well.

PMID- 15871598
TI  - Individual differences in auditory processing in specific language impairment: a
      follow-up study using event-related potentials and behavioural thresholds.
AB  - It has frequently been claimed that children with specific language impairment
      (SLI) have impaired auditory perception, but there is much controversy about the
      role of such deficits in causing their language problems, and it has been
      difficult to establish solid, replicable findings in this area. Discrepancies in
      this field may arise because (a) a focus on mean results obscures the
      heterogeneity in the population and (b) insufficient attention has been paid to
      maturational aspects of auditory processing. We conducted a study of 16 young
      people with specific language impairment (SLI) and 16 control participants, 24 of
      whom had had auditory event-related potentials (ERPs) and frequency
      discrimination thresholds assessed 18 months previously. When originally
      assessed, around one third of the listeners with SLI had poor behavioural
      frequency discrimination thresholds, and these tended to be the younger
      participants. However, most of the SLI group had age-inappropriate late
      components of the auditory ERP, regardless of their frequency discrimination. At
      follow-up, the behavioural thresholds of those with poor frequency discrimination
      improved, though some remained outside the control range. At follow-up, ERPs for
      many of the individuals in the SLI group were still not age-appropriate. In
      several cases, waveforms of individuals in the SLI group resembled those of
      younger typically-developing children, though in other cases the waveform was
      unlike that of control cases at any age. Electrophysiological methods may reveal
      underlying immaturity or other abnormality of auditory processing even when
      behavioural thresholds look normal. This study emphasises the variability seen in
      SLI, and the importance of studying individual cases rather than focusing on
      group means.

PMID- 15871599
TI  - Neural correlates of eye-gaze detection in young children with autism.
AB  - Various reports have demonstrated difficulties in eye-gaze processing in older
      children and adults with autism. However, little is known about the neural or
      developmental origin of such difficulties. In the present study, we used high
      density Event-Related Potentials (HD-ERPs) to record the neural correlates of
      gaze processing in young children with autism, and their age-matched controls. In
      addition, to determine normal gaze processing development we also tested a non
      autism adult group. The data obtained from the children with autism resembled
      that previously observed in typical 4-month old infants. In contrast, the control
      group showed the same pattern as typical adults. These findings suggest that the
      neural correlates of gaze direction processing may be delayed in young children
      with autism.

PMID- 15871600
TI  - Children's reading performance is correlated with white matter structure measured
      by diffusion tensor imaging.
AB  - We investigated the white matter structure in children (n = 14) with a wide range
      of reading performance levels using diffusion tensor imaging (DTI), a form of
      magnetic resonance imaging. White matter structure in a left temporo-parietal
      region that had been previously described as covarying with reading skill in
      adult readers also differs between children who are normal and poor readers.
      Specifically, the white matter structure measured using fractional anisotropy
      (FA) and coherence index (CI) significantly correlated with behavioral
      measurements of reading, spelling, and rapid naming performance. In general,
      lower anisotropy and lower coherence were associated with lower performance
      scores. Although the magnitude of the differences in children are smaller than
      those in adults, the results support the hypothesis that the structure of left
      temporoparietal neural pathways is a significant component of the neural system
      needed to develop fluent reading.

PMID- 15871601
TI  - Gamma abnormalities during perception of illusory figures in autism.
AB  - This experiment was designed to test the hypothesis that perceptual abnormalities
      in autism might be associated with alteration of induced gamma activity patterns
      overlying visual cortical regions. EEG was recorded from six adolescents with
      autism and eight controls matched on chronological age, and verbal and nonverbal
      mental age, whilst identifying the presence or absence of an illusory Kanizsa
      shape. Although there were no reaction time or accuracy differences between the
      groups there were significant task-related differences in cortical activity.
      Control participants showed typical gamma-band activity over parietal regions at
      around 350 msec post onset of shape trials, similar to gamma patterns found in
      previous studies with non-impaired adults. In contrast, autistic participants
      showed overall increased activity, including an early 100 msec gamma peak and a
      late induced peak, 50 to 70 msec earlier than that shown by the control group. We
      interpret the abnormal gamma activity to reflect decreased "signal to noise" due
      to decreased inhibitory processing. In this experiment we did not establish a
      link between altered perception and abnormal gamma, as the autistic participants'
      behaviour did not differ from the controls. Future work should be designed to
      replicate this phenomenon and establish the perceptual consequences of altered
      gamma activity.

PMID- 15871602
TI  - Abnormal brain activity related to performance monitoring and error detection in
      children with ADHD.
AB  - Brain electrical activity associated with inhibitory control was recorded in ten
      ADHD and ten healthy children using high density event related potentials (ERPs)
      during the Stop Signal Task (SST). SST is a two-choice reaction time (RT)
      paradigm, in which subjects are required, on 25% of the trials, to withdraw their
      response upon presentation of a "Stop Signal". In the healthy children, the ERP
      evoked by the Stop Signal differed for successful inhibitions (SI) compared to
      failed inhibitions (FI), with greater amplitude of a positive wave peaking around
      320 msec over anterior medial frontal scalp (P3a). Such success-related P3a
      activity was significantly reduced in amplitude in the ADHD group. In addition,
      the error related negativity (ERN), a sharp negative wave that is present
      selectively on error trials in choice RT experiments, peaking 100 ms after motor
      onset, and distributed over anterior medial frontal scalp, was also markedly
      reduced in the ADHD group. The scalp distribution of the group differences in P3a
      and the ERN is consistent with a reduction of activity of sources in dorsal
      anterior cingulate cortex (dACC), suggesting a global deficit in cognitive
      control operations subserved by dACC in ADHD.

PMID- 15871603
TI  - Impaired cerebellar learning in children with prenatal alcohol exposure: a
      comparative study of eyeblink conditioning in children with ADHD and dyslexia.
AB  - Neuroanatomical and behavioral evidence indicate that the cerebellum is
      particularly vulnerable to the toxic effects of prenatal alcohol exposure. Recent
      research has shown impairments in eyeblink conditioning in rats following binge
      like neonatal ethanol exposure. The neural substrates of eyeblink conditioning
      have been localized to the cerebellum and related brainstem mechanisms. The
      present study considered whether heavy prenatal alcohol exposure would result in
      similar impairments in eyeblink conditioning in children. A related purpose was
      to determine if eyeblink conditioning could discriminate between children with
      prenatal alcohol exposure and children diagnosed with attention deficit
      hyperactive disorder or developmental dyslexia. Fifty-three age-matched children
      [10 prenatal alcohol exposure (FAE), 16 attention deficit hyperactive disordered
      (ADHD), 14 children with dyslexia (DYS), 13 normal controls] were assessed on
      eyeblink conditioning in the delay paradigm. Children in the FAE and DYS groups
      failed to learn the conditioned response, producing longer latencies and poorly
      timed responses to the conditioning stimulus. Children with ADHD were impaired on
      measures of adaptively timed responses, although conditioned responses matched
      normal controls. The results suggest that children prenatally exposed to alcohol
      have deficits in cerebellar processing similar to those with dyslexia, and that
      these functional deficits are related to disabilities in learning.

PMID- 15871604
TI  - Specific language impairment is not specific to language: the procedural deficit
      hypothesis.
AB  - Specific Language Impairment (SLI) has been explained by two broad classes of
      hypotheses, which posit either a deficit specific to grammar, or a non-linguistic
      processing impairment. Here we advance an alternative perspective. According to
      the Procedural Deficit Hypothesis (PDH), SLI can be largely explained by the
      abnormal development of brain structures that constitute the procedural memory
      system. This system, which is composed of a network of inter-connected structures
      rooted in frontal/basal-ganglia circuits, subserves the learning and execution of
      motor and cognitive skills. Crucially, recent evidence also implicates this
      system in important aspects of grammar. The PDH posits that a significant
      proportion of individuals with SLI suffer from abnormalities of this brain
      network, leading to impairments of the linguistic and non-linguistic functions
      that depend on it. In contrast, functions such as lexical and declarative memory,
      which depend on other brain structures, are expected to remain largely spared.
      Evidence from an in-depth retrospective examination of the literature is
      presented. It is argued that the data support the predictions of the PDH, and
      particularly implicate Broca's area within frontal cortex, and the caudate
      nucleus within the basal ganglia. Finally, broader implications are discussed,
      and predictions for future research are presented. It is argued that the PDH
      forms the basis of a novel and potentially productive perspective on SLI.

PMID- 15871605
TI  - Characterising compensation. (Commentary on Ullman and Pierpont, "Specific
      language impairment is not specific to language: the procedural deficit
      hypothesis").
AB  - This article considers Ullman and Pierpont's Procedural Deficit theory of
      Specific Language Impairment (SLI). The theory represents an innovative attempt
      to fill the gap between brain and cognition in SLI, and has the potential to
      explain the non-linguistic as well as linguistic deficits seen in this disorder.
      The theory is reviewed with regard to: (1) the claims it makes on the domain
      specificity of language structures; (2) the falsifiability conditions of the
      theory; (3) the level of detail at which compensatory processes are specified;
      and (4) from a computational perspective, whether the inferences that the theory
      draws from uneven behavioural impairments to underlying structural deficits are
      necessary ones.

PMID- 15871606
TI  - Vestibular evaluation in Behcet's disease. Personal experience.
AB  - Few reports have appeared in the literature concerning vestibular findings in
      Behcet's disease. In the present study, extensive vestibular testing, performed
      in 14 patients (8 male, 6 female; mean age: 32 years; range: 12-51) presenting
      definite Behcet's disease, revealed a high prevalence of central vestibular
      dysfunctions (78%). Data reported here suggest that an otoneurological evaluation
      of Behcet's disease patients may be helpful in identifying unexpected vestibular
      dysfunctions and central nervous system involvement different from the classical
      manifestations of the neuro-Behcet's syndrome.

PMID- 15871607
TI  - Oncological and functional results of CO2 laser cordectomy.
AB  - Laser surgery represents the evolution of endoscopic surgery and, as far as
      concerns treatment of laryngeal tumours, CO2 laser cordectomy is considered a
      valid alternative to conventional surgery (laryngofissure cordectomy) and to
      exclusive radiotherapy for glottic carcinomas, classified as T1a, T1b and T2. The
      present report focuses on personal experience with CO2 laser cordectomy over the
      last 11 years, evaluating oncological and functional results. Between October
      1990 and December 2001, micro-laryngoscopy has been performed with CO, laser, in
      606 cases (benign and malignant lesions), of which 150 laser cordectomies, at the
      ORL Department, Eastern Piedmont University of Novara. An analysis is made of 63
      patients (mean age 64.3 years) who underwent laser cordectomy for glottic
      carcinoma, observed at follow-up for at least 3 years. Vocal function has been
      studied on a sample of 20 patients. Of those who underwent CO2 laser cordectomy
      for T1a and T1s, 95.8% were disease free after a minimum of 3 years follow-up.
      Video-larynx-stroboscopic test highlighted the presence of a "satisfying" fibrous
      neocord in cases treated with Type III cordectomy. The speech compensation was of
      the "cord-neocordal" type (35%), false cordal (40%) and with arytenoideus
      hyperadduction (25%). The electro-acoustical analysis of the voice highlighted a
      "serious dysphonia" compatible with Type IV cases according to Yanagihara (70%)
      and moderate-severe dysphonia (30%). Mean values of vocal parameters were 5.8%
      for Jitter, 12.2% for Shimmer, 0.34 for NHR. CO2 laser cordectomy is first choice
      treatment for T1a glottic carcinoma, offering intra- and post-operative
      advantages: reduced traumatism, lack of tracheostomy, low bleeding, fast
      functional recovery (deglutition and speech), brief hospital stay, and low
      management costs. Dysphonia resulting from treatment, characterised by breathed
      voice, allows the patient to lead a normal life.

PMID- 15871608
TI  - Current radiotherapic procedures and preservation of salivary function in
      patients with head and neck cancer.
AB  - Head and neck tumours have poor prognosis: with surgery and radiotherapy, local
      control is achieved but is associated with damage to speech and swallowing
      function. Conventional 2-D radiotherapy is based on one fraction of 1.8-2.0 Gy
      per day; increasing the number of fractions, a higher dose can be administered,
      with an increase in local control. Today, conventional treatment can be replaced
      by new techniques: with 3-D Conformal Radiotherapy, higher doses of radiation can
      be delivered to cancer cells while reducing the amount of radiation received by
      surrounding healthy tissues: Intensity Modulated Radiation Therapy permits an
      irregular dose distribution that conforms exactly to the volume of the target,
      increasing local tumour control and survival and decreasing radiation-induced
      side-effects.

PMID- 15871609
TI  - Topical versus systemic diclofenac in the treatment of temporo-mandibular joint
      dysfunction symptoms.
AB  - The most frequent symptom of craniomandibular dysfunction is pain in the
      preauricular area or in the temporo-mandibular joint, usually localized at the
      level of the masticatory musculature. Patients sometimes also complain of reflect
      otalgia, headaches and facial pain. Osteoarthrosis is a frequent degenerative
      debilitating chronic disorder that can affect the temporomandibular joint. It
      causes pain and articular rigidity, a reduction in mobility, and radiological
      alterations are visible in stratigraphy. The aim of this study was to compare the
      efficacy of a topically applied non-steroid anti-inflammatory drug that has
      recently become commercially available (diclofenac sodium in a patented carrier
      containing dimethyl sulfoxide, that favours transcutaneous absorption) which is
      commonly used to alleviate pain in knee or elbow joints, versus oral diclofenac,
      in the treatment of symptoms of temporomandibular joint dysfunction. Dysfunction
      of the temporomandibular joint was diagnosed in 36 adult patients. The patients
      were randomized in two age- and gender -matched groups. Group A (18 patients)
      received oral diclofenac sodium administered after a meal in 50-mg tablets twice
      a day for 14 days. Group B (18 patients) received 16 mg/ml topical diclofenac
      (diclofenac topical solution, 10 drops 4 times a day for 14 days). All patients
      completed a questionnaire at the start and end of therapy. Patients were asked to
      quantify on a graded visual analogue scale and to reply to questions about the
      pain and tenderness of the temporomandibular joint and the functional limitation
      of mouth opening. Patients were also requested to report side-effects of the
      treatment. All patients showed relief from pain after treatment: the difference
      between the two groups was not significant (p > 0.05). Post-treatment, 16
      patients of group A had epigastralgic symptoms. Three patients treated with
      topical diclofenac showed a modest irritation of the temporomandibular joint
      region, and disappeared spontaneously. Our results demonstrate that topically
      applied diclofenac and oral diclofenac are equally effective in the treatment of
      temporomandibular joint dysfunction symptoms. Topical diclofenac has the
      advantage that it does not have adverse systemic effects, whereas oral diclofenac
      had untoward effects on the gastric apparatus. The efficacy of diclofenac
      topically applied on the temporomandibular joint region observed in group B is
      explained by the association of diclofenac with dimethyl-sulfoxide, which enables
      a rapid effective penetration into the joint tissues. It is noteworthy that
      dimethyl-sulfoxide favours transuctaneous absorption when used in a multi-dose
      regime as in our study with 4 doses a day. Thus, single, "as required",
      applications should be avoided because this practice results in scarce absorption
      of diclofenac.

PMID- 15871610
TI  - Vertebral artery dissection as a rare cause of vertigo: case report.
AB  - Vertebral artery dissection is one of the more frequent cerebral-vascular
      disorders in the young adult. The initial symptoms rarely consist of vertigo with
      clinical characteristics of Selective Monolateral Acute Vestibular Deficit
      Syndrome. The case is described of a patient, who arrived with intense rotatory
      vertigo associated with neurovegetative symptoms and spontaneous nystagmus, which
      we initially diagnosed as right neuronitis. About 48 hours later, the symptoms of
      vertigo disappeared spontaneously, and prevalently nuchal cephalea appeared.
      Since the symptoms were atypical and the otoneurologic study revealed normal
      canalar and otholithic function, a cerebral nuclear magnetic resonance, with
      contrast, was carried out which showed the presence of multiple areas of
      cerebellar ischaemia, prevalently on the left, and at the level of the right
      occipital lobe. Study of the patient was completed with an intracranial angio
      nuclear magnetic resonance of the neck arteries and cerebral angiography the
      findings of which were compatible with left vertebral artery dissection. It is
      important to emphasize, as reported in the literature, that in cases in which
      atypical evolution of the pathology appears, or instrumental data do not confirm
      initial suspicions, a more scrupulous study is always necessary in order to find
      a possible central cause. Among the central causes, it should not be forgotten
      that multiple small cerebellar strokes (more frequent in elderly patients) and
      even more rarely also vertebral artery dissection (which is typical of younger
      patients) may become evident in a clinical picture that is almost identical to
      that seen in selective monolateral acute vestibular deficit syndrome.

PMID- 15871611
TI  - Fibrous dysplasia of middle turbinate associated with Widal syndrome: endoscopic
      treatment of a rare case.
AB  - Fibrous dysplasia, a rare bony disease, is characterised by substitution of
      normal bone with immature tissue embedded in a fibrous stroma. It can be either
      monostotic or involve several bones. Fibrous dysplasia is usually asymptomatic
      but, in the advanced stage, pain due to neural compression or pathological
      fractures may occur. In the case of cranio-facial involvement, ocular,
      masticatory, respiratory or auditory functional alterations are possible. A case
      of fibrous dysplasia, limited to the middle turbinate and associated with Widal
      triad (sinus-nasal polyposis, asthma, acetyl salicylic acid intolerance), is
      described. Craniofacial computed tomography revealed enlargement of left middle
      turbinate with characteristic "ground-glass" appearance. The patient underwent
      anterior bilateral functional endoscopic sinus surgery with near-total resection
      of left middle turbinate. Histopathological examination confirmed the diagnosis
      of fibrous dysplasia. After 2 years the patient is still asymptomatic.
      Videorhinoscopy shows good sinus-nasal patency without disease recurrence. Even
      though exceptional, localization of fibrous dysplasia at middle turbinate has
      been described, therefore, it must be considered in the differential diagnosis of
      the craniofacial ossifying disorder. For localized and symptomatic lesions,
      endoscopic surgery is an effective option. Scrupulous life-long follow-up is
      necessary due to the high percentage of recurrence and possible malignant
      degeneration.

PMID- 15871612
TI  - Endoscopic treatment of maxillary sinus mucocele.
AB  - Four patients with mucocele of maxillary sinus, observed between 1995 and 2001,
      with two years' follow-up, are described. Aim of the present study was to
      establish whether endoscopic marsupialization of the maxillary sinus mucocele is
      adequate resolutive treatment without complete removal of the mucocele wall,
      using more invasive approaches. The surgical procedure used was endoscopic
      endonasal marsupialization by a middle and/or inferior meatal antrostomy. Outcome
      confirms that this technique is the gold standard treatment in this disorder. In
      fact, complete removal of the mucocele wall is not necessary thus avoiding the
      risk of iatrogenic lesions of neighbouring structures in the case of a bony
      erosion (orbital floor, posterior wall of the maxillary sinus).

PMID- 15871613
TI  - Giant osteoid osteoma of ethmoid sinus: role of functional endoscopic sinus
      surgery.
AB  - A case of giant ethmoid osteoma treated by functional endoscopic sinus surgery is
      described. The tumour was closely adherent to the surrounding anatomical
      structures--lamina papyracea, cribriform plate, spheno-ethmoidal recess--and
      protruded into the nasopharynx. Complete removal of the tumour, under general
      anaesthesia, using intranasal drill and diode L.A.S.E.R, was achieved. The
      principal aspects in favour of this surgical technique vs. open procedures
      (fronto-basal craniotomy, supraciliar and coronal approach) are discussed.
      Functional endoscopic sinus surgery is herewith concluded to be a convenient and
      safe technique with advantages over the open procedures, widely used in the past.
      The reduced morbidity, length of hospital stay and better cosmetic results are
      distinct advantages of this technique that has the potential to become the
      treatment of choice for selected ethmoid tumours, such as giant osteoma,
      described in the present report.

PMID- 15871615
TI  - [Health inequalities among occupations: epidemiologic hints for labour and social
      protection policies].
AB  - BACKGROUND: Based on existing information systems in Italy, a program can be
      created for monitoring and surveillance of occupational differences in health. In
      recent years, a number of proposals were made for defining wearing-out jobs and
      for reforming the retirement age and/or required number of years of
      contributions: on these occasions the need to create a programme for monitoring
      occupational health was stressed. To this end, ISPESL (the National Institute of
      Occupational Safety and Prevention), in cooperation with the Epidemiology Unit of
      the Piedmont Region of Italy, assessed the validity of epidemiological indicators
      from existing sources and their use in creating a surveillance system of wearing
      out jobs. OBJECTIVES: The main results of the evaluations performed to date are
      presented herein. The results are discussed in relation to the information needs
      for developing both health policies and other types of policies addressing
      occupation. MATERIALS AND METHODS: Each of the articles in this issue deals with
      a specific model (based on information sources available in Italy in the 1990's)
      for studying the relationship between health [general and cause-specific
      mortality; accidents and accident proneness; the main causes of chronic morbidity
      (cancer, diabetes, and vascular and respiratory diseases); self-reported health:
      perceived health, chronic illnesses; absenteeism, lifestyles, stress, working
      conditions] and occupation (most recent occupation or the main lifetime
      occupation recorded by the specific information source, using a 55-item
      classification created especially for this research). Here, the statistically
      significant associations are compared with data in the literature and discussed
      in light of the information needs for developing health policies and other
      pertinent policies. RESULTS: For men, the data on health indicators taken from
      the available information sources were adequate for identifying occupational
      differences in health. Certain occupations were consistently disadvantaged:
      masons and construction vehicle operators, transport-vehicle operators, miners,
      quarry workers, and agricultural workers. Foundry workers and forgers showed less
      consistent excesses. A greater risk for the majority of health indicators
      considered was also observed for those manual jobs that require fewer specialised
      skills: cleaning staff refuse collectors, and waste-treatment workers; porters
      and unloaders; custodians and watchmen. Among women, the health indicators were
      much more dissociated: the gender differences seem to precede the occupational
      differences and require the planning of a more precise and sensitive system. The
      occupational differences in health represent the final outcome of exposure not
      only to occupational risk factors but also to psycho-social factors (e.g.,
      nutritional, environmental, and relational problems in early childhood;
      lifestyles; difficult access to timely and effective healthcare), which must thus
      be taken into account when evaluating retirement age; to ensure that workers have
      equality of treatment. The synoptic and integrated use of diverse information
      sources was extremely complex. Whereas an occupation may show excess risk for
      health indicators derived from one source, the same occupation may not
      necessarily show the same excess when the indicators are derived from another
      source. This can be attributed to: the limited specificity of the classification
      system; low statistical power; the possibility that the presence of excesses
      (e.g., in mortality and morbidity) may simply be due to chance; the local or
      specific nature of the information source; the level of specificity or
      sensitivity of the health indicators to the risk factors. CONCLUSIONS: The
      studies described in this issue demonstrate that if the existing information
      sources in Italy are integrated through proper record-linkage, they can be used
      to follow health outcomes over time in relation to occupational history or
      income, providing useful information for developing or revising retirement
      policies. If it were possible to progress from this phase of evaluation of
      predictive validity of the informative sources examined, to the implementation of
      their routine use in conducting studies and surveillance of health inequalities
      between occupations, Italy would gain a place in the forefront in Europe in this
      field.

PMID- 15871614
TI  - Tonsillolith. Case report and review of the literature.
AB  - Large oropharyngeal concretions--giant tonsillolith--are not very common. Over
      the last few years only some 50 cases have been reported in the literature. Many
      tonsilloliths, especially small concretions, are asymptomatic; large concretions,
      on the contrary, may produce several symptoms. The case is described of a 56-year
      old female complaining of dysphagia, odynophagia, sore throat, right otalgia and
      swelling in right tonsillar fossa. Routine panoramic radiography revealed a radio
      opaque area in right tonsil region. Computed tomography of oropharynx was
      performed and axial slices revealed a calcified cylindrical lesion in posterior
      pharyngeal region, between palatoglossus and palatopharyngeus muscles. The
      tonsillolith was easily excised under local anaesthesia. The post-operative
      course was good with no recurrence. Microscopic examination of the specimen
      revealed necrotic debris, "ghost" cells, calcifications and inflammatory cells,
      confirming the diagnosis of tonsillolith. Authors stress that large tonsillar
      concretions are uncommon, and may be difficult to diagnose since the tonsillolith
      can also be mistaken for other anatomic and pathologic structures in the
      oropharyngeal area.

PMID- 15871616
TI  - [Healthy life expectancy in the occupied segment of the Turin population].
AB  - BACKGROUND: The indicators of healthy life expectancy measure differences in
      health among various population subgroups more sensitively than do indicators of
      mortality. OBJECTIVES: The aim of the study was to analyze some of the above
      indicators to evaluate the differences among occupational categories in Turin.
      METHODS: Mortality tables by occupation were calculated on Turin residents, aged
      18-64 years in 1991, using the Turin Longitudinal Study which combines personal,
      census, and health information for the residents of the city. Longitudinal
      assessments of health expectancy were obtained by means of record-linkage with
      the Cancer Registry, the Diabetes Registry, and hospital discharge records. In
      addition, prevalence estimates of good health, disability, and chronic illness,
      obtained from ISTAT (Central Statistics Institute) investigations in 1999-2000
      were combined with mortality data using Sullivan's algorithm. RESULTS: Among men
      there was a systematic disadvantage in almost all indicators of health expectancy
      for some manual occupations, while jobs requiring more qualifications were more
      advantaged. The health profile for women was more controversial, with an overall
      disadvantage among women who were professional consultants, although this group
      showed substantial variability: the legal professions had the lowest life and
      health expectancies, with approximately 3 years of life less than the health
      professions, which were among the most advantaged. DISCUSSION: The various
      indicators gave results which were at times conflicting, especially because the
      information obtained from the available sources had major limitations. The
      development of indicators needs to aim for greater homogeneity between mortality
      and health data to ensure maximum comparability.

PMID- 15871617
TI  - [Occupational mortality in the population employed at 1991 Census].
AB  - BACKGROUND: Despite limitations and problems connected to occupational
      surveillance systems based on mortality data, mortality from specific causes
      continues to be a crucial indicator for evaluating the differences in health
      among various occupations. OBJECTIVES: To evaluate the potential of a
      surveillance system of occupational mortality based on census and mortality data
      obtained from ISTAT (Italian Central Statistics Institute). METHODS: By means of
      record-linkage between Census data and death records from ISTAT, occupational
      mortality was assessed during the twelve month period following the 1991 census,
      limited to subjects aged 18-64 years for whom occupational information was
      available. The study population consisted of deceased subjects, 19,527 of whom
      were men and 3,547 were women. A cross-sectional model was used to evaluate odds
      ratios for cause-specific mortality. The risk estimates were then compared to the
      results obtained in a previous analysis on Census data gathered in the 1981
      census. RESULTS: Among the significantly increased risks observed both in 1981
      and 1991, of particular interest are the excesses of mortality from liver
      cirrhosis in caretakers, janitors, and cleaning staff; and the excess of breast
      cancer in teachers. Mortality from cirrhosis in masons, porters, and waiters, and
      from violent causes in transport workers and bar and restaurant workers, was
      instead significantly in excess only in 1991. CONCLUSIONS: The data on mortality
      by occupation does not permit inferences about occupational risks, though they
      can be useful to highlight socio-economic differences in premature death in the
      employed segment of the population and to draw attention to possible trends over
      time.

PMID- 15871618
TI  - [Occupational mortality in Italy during 1992, assessed through record-linkage
      between pension records and death certificates].
AB  - BACKGROUND: The creation of a surveillance system of occupational mortality in
      Italy is limited by the low quality of information on occupation in death
      certificates, since the information is often incomplete or lacking and because
      only the occupation at the time of death is registered. OBJECTIVE: To evaluate
      the possible use of INPS (National Institute of Social Security) records for the
      purpose of surveillance of occupational mortality, in terms of feasibility of
      setting up a system and of validity of the results obtained. METHODS: Death
      records of 218,510 subjects aged 18-74, deceased in the 12 months following the
      1991 census, were obtained from ISTAT (Central Statistics Institute). These were
      combined through record-linkage with the INPS social security archives, which
      contain the employment records by economic sector going back to 1974, in order to
      assign these deaths the sector in which they had worked the longest. Mortality by
      specific causes was evaluated by industry by means of a proportional mortality
      analysis stratified by sex and occupational status, and adjusted for age,
      education, marital status, geographical area of birth, drawing a disability
      pension, employment status at the time of death and work instability. RESULTS:
      Record-linkage allowed attribution of the longest held job to 70% of the deaths
      recorded. Results are presented and discussed only on mortality in men due to
      asbestosis and silicosis, and causes of death with a substantial proportion
      attributable to occupation: chronic obstructive pulmonary disease (COPD); cancers
      of the bladder, nasal cavity, larynx, lung and pleura; leukaemia and lymphoma;
      accidental causes. Among the economic sectors with a significant excess
      mortality, the following are well documented in the literature: mortality due to
      COPD in the coal and peat-bog sectors; due to leukaemia among farmers; due to
      sino-nasal tumours in wood-working and furniture production; due to cancer of the
      larynx, lung, and pleura in occupations where there was probable exposure to
      asbestos (fishing and maritime transport, non-metal mining, building industry,
      and naval, train and aircraft construction); due to silicosis in industries with
      potential exposure to crystalline silica; due to accidental causes in the
      building industry and farming. Other mortality excesses and deficits, especially
      those due to bladder and lympho-haemopoietic cancers, appear to be only partly
      consistent with those described by other authors. DISCUSSION: The feasibility of
      developing a surveillance system of occupational mortality based on the INPS
      source was found to be good, and, at least among males, for 75% of the deceased
      subjects historical information existed concerning the economic sectors
      registered in the INPS records. The results obtained would appear to indicate
      that the system is capable of highlighting risk excesses due to widespread
      exposure in the industries examined, regarding diseases for which there is a
      strong association with exposure. On the other hand, due to the inherent limits
      of the study's design (lack of a complete work history and of precise information
      on the jobs held) its use is not recommended in the surveillance of diseases with
      a low proportion attributable to a risk factor, or with wide exposure variability
      in a given sector among the various jobs.

PMID- 15871619
TI  - [Differences of perceived health and lifestyle by occupational groups in the
      Italian ISTAT (Central Statistic Institute) health survey].
AB  - BACKGROUND: Little is known about the distribution by occupation of chronic
      illness, disability, morbidity, and lifestyles which put health at risk.
      OBJECTIVES: To provide a map of the social inequalities in various dimensions of
      health and lifestyle by social class and for specific occupational groups. To
      formulate a hypothesis about the mechanisms which generate these inequalities.
      METHODS: Prevalence rate ratios and prevalence odds ratios of perceived health,
      chronic illness, disability, absenteeism, trauma, smoking, and obesity calculated
      with data from the 1999-2000 Italian ISTAT (Central Statistics Institute) health
      survey; the study population includes adults (aged over 18 years) employed, or
      searching for a job, or withdrawn from the workforce. RESULTS: Among workers in
      manual unskilled labour, construction and agriculture are noted for worse health
      and more unhealthy lifestyles than average. For example, perceived bad health is
      more widespread among agricultural labourers (OR = 1.63), masons and construction
      machine operators (OR = 1.75), transport drivers (OR = 1.40), male caretakers,
      custodians, janitors and domestic help (OR = 1.46), electro-technicians (OR =
      1.44), leatherworkers and shoemakers (OR = 3.58), miners and quarrymen (OR =
      2.60), earthenware and stone workers (OR = 2.14), garment and furnishings workers
      (OR = 1.86); in female workers excess risk for perceived bad health was present
      among agricultural labourers (OR = 2.08), caretakers, custodians, janitors and
      domestic helpers (OR = 1.49), waitresses, cooks and bartenders, (OR = 1.44), and
      textile workers (OR = 1.67). Smoking was more widespread among chemical workers
      (OR = 1.41), and in miners and quarrymen (OR = 1.30). An excess risk of smoking
      of 20-25% was evident in spinners, weavers and finishers; masons, (and) builders;
      waiters, cooks and bartenders; garment and furnishings workers; porters and
      warehouse workers. The risk was 10% higher among foundry workers and forgers,
      plumbers, carpenters and welders, and transport drivers. Among women the
      propensity to smoke was higher among waitresses, cooks and bartenders (OR =
      1.37), cleaners, commerce and service workers (OR = 1.22). Other occupational
      groups with an increased smoking prevalence, where women were less represented,
      included: chemical workers (OR = 2.25), butchers (OR = 1.97), postwomen (OR =
      1.58), plastics workers (OR = 1.56), shippers (OR = 1.37). CONCLUSIONS: It can be
      hypothesized on the one hand that there are factors and mechanisms common to the
      various occupational groups belonging to the same social class; on the other,
      there are factors and mechanisms specific to certain occupational categories. The
      latter can generate specific health subcultures. A greater integration between
      qualitative and quantitative research is recommended, which would yield better
      explanations of the observed inequalities.

PMID- 15871620
TI  - [Workplace injuries and professional mobility correlated with health problems.
      The potential and limitations of the ISTAT Labour Force survey--July 1999].
AB  - BACKGROUND: Knowledge on the occupational and social factors that influence the
      relationship between illness, absence from work and occupational mobility is at
      present insufficient. OBJECTIVES: To map out, by social class and occupational
      group, the impact of health problems on work and the distribution of accidents
      and morbidity associated with occupation. METHODS: Using data from the National
      Survey of the Italian Labour Force (ISTAT, 1999), covering a sample of 200,384
      subjects, prevalence odds ratios of morbidity, work injuries and change of
      occupation due to health problems were calculated by social class and occupation,
      adjusting for age and residence. RESULTS: The working class showed a higher risk,
      due to health problems, of a reduction in time worked (OR = 3.70 in men and OR =
      4.10 in women), of choosing to work part-time (OR = 2.04 in men and OR = 2.27 in
      women), or of withdrawing from the workforce (for artisans, skilled manual
      workers, farmers and agricultural labourers OR = 1.63 in men and OR = 1.47 in
      women). This class was also at a greater disadvantage not only with respect to
      accident rates (OR = 1.85 in men and OR = 1.88 in women), but also with respect
      to the time needed for post-trauma rehabilitation and return to work (for
      absences of one week to one month: OR = 1.67 and 1.83 for men and women,
      respectively; for absences of more than one month: OR = 1.29 and OR = 1.69).
      Moreover, the working class, when compared to other social classes, had a higher
      rate of suffering from illness, physical impairment or other physical and
      psychological problems caused or aggravated by working activity (25% in men and
      32% in women). CONCLUSIONS: The ISTAT National Survey provides an estimate of
      minor accidents with prognoses of less than three days, including those not
      reported to the National Institute for Insurance against Occupational Accidents
      and Diseases (INAIL). This allows a preliminary exploration of the relationship
      between health problems and occupational mobility; however, it seems necessary to
      collect more detailed information in order to more exhaustively explore the
      mechanisms which generate the inequalities observed.

PMID- 15871621
TI  - [Risk of workplace injuries by occupation in Italy in the 1990's].
AB  - BACKGROUND: In Italy it is not possible to assess the incidence of workplace
      injuries by occupation due to the absence of denominator data. OBJECTIVES: To
      evaluate severe workplace injuries by occupation, age and gender, via discussion
      of the validity of the available methods and informative systems. METHODS: The
      database included injuries in the industrial and artisan sectors in Italy during
      the period 1995-1999, as classified by INAIL (National Institute for the
      Insurance against Occupational Accidents and Diseases). A proportional case
      control study was used. Three types of severe injuries were analyzed: fatal
      (3,685), permanently disabling (88,254) and injuries resulting in temporary
      disability for more than 40 days (238,609). Controls were represented by minor
      injuries with temporary disability lasting between 8 and 13 days (512,643). The
      relative risks were calculated by occupation and stratified by age and sex. The
      control group was chosen in order to minimize distortions and represented a
      balance between empirical criteria based on the experience of safety technicians
      and the quality and limits of INAIL archives. RESULTS: Among men in some
      construction occupations (operators of construction equipment, crane operators
      and masons), and in truck drivers, farm workers, messengers, and miners there
      were elevated risks in all age groups and for all levels of injuries severity.
      The model was more problematic to apply to women because the control group was
      less representative of the work population at risk. CONCLUSIONS: The case-control
      study model produced results consistent with those in the international
      literature, even if the use of minor injuries as the control group gives partly
      distorted risk estimates. The results supply information for decision making and
      for allocating resources for prevention and safety.

PMID- 15871622
TI  - [Severity of workplace injuries by occupation in Italy in the 1990's].
AB  - BACKGROUND: The indicators of severity commonly used for studying workplace
      injuries are somewhat limited. It is possible to use RIDIT Analysis (Relative to
      an Identified Distribution) as an alternative method OBJECTIVES: To order
      occupations in Italy by severity of workplace injuries and discuss the
      methodological problems and the outcomes from available administrative data.
      METHODS: The database included injuries defined by INAIL (National Institute for
      Insurance against Occupational Accidents and Diseases) in Italy in the period
      1995-99 in the industrial and artisan sectors (1,647,220 events). RIDIT Analysis
      was applied using Bross analysis of ordinal data. A distribution of injuries in
      Italy for the same period on a six-level scale of severity was used as a
      reference. The RIDIT value for each occupation was calculated and stratified by
      age, sex, and occupational sector. RESULTS: Among men, the occupations in which
      injuries were more severe than the average in Italy were construction, transport,
      woodworking, and mining. Above-average injury severity among women was found in
      transport drivers, postwomen, messengers, and workers in performing arts, the
      food industry, and tourism. A positive relationship between age and severity of
      injury was observed in all occupations in both sexes. Average severity was higher
      among artisans. CONCLUSIONS: The method used allows ranking of occupations
      according to injury severity and should be systematically introduced into
      existing systems of surveillance so that data can be used to foster prevention
      and workplace safety.

PMID- 15871623
TI  - [Risk of repeated injuries by economic activity in Italy in the 1990's].
AB  - BACKGROUND: Repetitive work injuries are a phenomenon that has not been
      sufficiently studied. Using data gathered by INAIL (National Institute for
      Insurance against Occupational Accidents and Diseases), it is possible to study
      the propensity of having a further injuries at the workplace after the first one.
      OBJECTIVES: To identify the risk of experiencing multiple injuries according to
      occupation, with discussion of how useful the available information systems are.
      METHODS: The data base includes workplace injuries, as classified by INAIL in
      Italy between 1994 and 2000 in the industrial and artisan sectors (2,162,702
      subjects, ages 25-55). Selecting data on accidents occurring among 107,082
      subjects who had experienced the first accident in 1996-99, in this cohort we
      assessed the occurrence of further accidents within two years in the same
      occupation, taking into account job mobility and factors eventually influencing
      underreporting (geographic area, age, severity of first accident and size of the
      enterprise). The risk for each occupation was computed stratifying by gender.
      RESULTS: There were significant differences between the first and successive
      accidents when examined by type, age group, severity of physical consequences and
      company size. Among men, the occupations showing higher risk were those already
      known to be at high risk for accidents: cleaning staff and refuse workers,
      foundry workers, masons, pilots, woodworkers, carpenters, transport workers,
      sailors, farmers, and miners. Among women the occupations most at risk were
      postwomen and messengers, cleaning staff and refuse workers, waitresses, cooks,
      bartenders, machine tool operators, woodworkers, and weavers in the textile
      industry. CONCLUSIONS: Among men, the risk of recurrent workplace accidents by
      occupation tends to reflect the frequency of the total accidents in each
      occupation. The results indicate that the study model employed is efficient and
      useful in providing risk profiles which allow identification of where to direct
      future studies, investigations, and preventive measures for each sex.

PMID- 15871624
TI  - [Occupational differences in exposure to hazardous work conditions].
AB  - BACKGROUND: Few studies have been aimed at describing organizational and
      psychosocial conditions of the Italian workforce by occupational group, and they
      have been mainly conducted within specific occupations. OBJECTIVES: The present
      study aimed at identifying specific groups of occupations which have unfavourable
      profiles from the point of view of exposure to specific organizational factors
      and psychosocial risks, and to physical, chemical and ergonomic risks, and
      analyzing their distribution by worker age. METHODS: The analysis was conducted
      on a sample of 4,195 workers in the Piedmont Region who were members of the CGIL
      Trade Union (Italian General Confederation of Labour), who answered a self
      administered questionnaire in 2000, aimed at assessing chemical, physical, and
      ergonomic risks, accidents, and psychosocial factors connected with work
      organization and work tasks. Psychosocial risks were assessed via three scales
      aimed at measuring the degree of control, psychophysical demands, and worker
      satisfaction. The proportion of workers exposed to the above mentioned risks was
      analysed according to occupational group. This group was then compared with all
      other groups taken together, according to prevalence of high strain condition
      (combination of high demand and low control) and HSUR condition (High Strain
      Unfairly Rewarded; combination of high strain and low satisfaction). RESULTS:
      Among males aged 25-44 years, restricted to the occupation groups with more than
      ten workers in high strain condition, significantly higher proportions of stress
      were observed in leather workers and shoemakers, paper factory workers, rubber
      workers, crane and bridge crane operators, plastic workers, painters, transport
      drivers and carpenters. For many of these groups, excesses were confirmed for the
      HSUR condition. Among subjects aged over 44 years, a higher risk for high strain
      was confirmed in rubber workers, transport drivers and carpenters. In addition,
      machine tool operators, assembly line and mechanical workers in this age group
      were exposed to higher risk of stress. In younger women there was a significantly
      higher risk of both high strain and HSUR conditions in workers employed in the
      rubber, plastic and the food industries, and in machine tool workers. Such excess
      risk was confirmed in the latter three categories also among older women. In
      general, the proportion of male workers classified as working in high strain
      conditions decreased as age increased, while in women it remained stable.
      CONCLUSIONS: The study allowed evaluation of the differential impact of exposure
      to physical, chemical, and psychosocial risk factors among occupational groups,
      thus contributing to the identification and classification of exhausting jobs.
      The results further showed, particularly among men, a smaller proportion of older
      workers, compared to younger ones, exposed to harmful physical, chemical,
      ergonomic and psychosocial conditions, indicating a possible propensity of
      companies to adapt workplace conditions, organization and internal mobility to
      worker age.

PMID- 15871625
TI  - [Study of the relationship among work and demographic characteristics, sickness
      absence and occupational mobility].
AB  - BACKGROUND: The problem of sick absences from work is correlated to a series of
      organizational, social and psychological factors which interact with risk factors
      typical of the work performed, and thus determine how frequently absences occur.
      The correlation between morbidity and work is of interest in itself for studying
      the processes of occupational mobility. OBJECTIVES: To examine, using data from
      administrative sources, the association of sick absence with individual and
      workplace factors, as well as the relationship between illness and career
      mobility. METHODS: Employee sick absence data registered at INPS (National
      Institute of Social Insurance) in the period 1992-95 were studied using a sample
      of 124,686 subjects. RESULTS: The probability of being absent from work due to
      illness did not appear to be affected by sex or age. The sectors more at risk for
      sick absences were the service sector, business and commerce. Inequalities were
      noted in illness rates to the disadvantage of those who had received redundancy
      payments in the previous years. New hirings and upward mobility were associated
      with a lower occurrence of illness. A higher probability of illness was observed
      in those who had lost their jobs and in those who had changed from full-time to
      part-time work. CONCLUSIONS: It is likely that formal regulations and practices
      in use within INPS vary according to the different economic activities. Therefore
      this source allows investigation of illness only in activities with homogeneous
      regulatory aspects. The results confirm a link between unstable work situations
      and illness and between illness and career advancement.

PMID- 15871626
TI  - [Use of pension records for occupational health surveillance: example of record
      linkage with hospital discharge records to study the association between work and
      the incidence of leukaemias, lung and bladder cancer, and miscarriage].
AB  - BACKGROUND: Epidemiologic surveillance of occupational health based on routinely
      collected data allows groups of workers to be studied, whose type of work (e.g.
      small enterprises, self-employed workers, artisans) makes it difficult to use a
      traditional cohort study design. OBJECTIVE: To evaluate the validity of a study
      design based on the record-linkage between hospital discharge records and INPS
      social security records (National Institute for Social Security), in order to
      investigate the association between past employment in an economic sector and
      occurrence of diseases with a low fraction attributable to occupation and a high
      frequency in the population, where it is too costly to perform retrospective
      interviews to gather data from each recruited subject. METHODS: A case-control
      study design was used in which hospital discharge records from 1995 in the
      Piedmont Region represented the source of subjects enrolled. Four series of cases
      were identified: males aged 40-75 years, with first hospital admission for
      leukaemia, lung or bladder cancer; and women aged 18-39 years, admitted for
      miscarriage. The controls were a random sample of patients admitted in the same
      year and matched by sex and age. The exposure variable was the prevalent economic
      sector in the occupational history of the subjects enrolled, as inferred from
      INPS social security records. RESULTS: No economic sector examined showed a
      significant excess of incidence of bladder cancer or leukaemia. There was a
      significant excess of lung cancer in subjects with longest employment in the
      building industry, in metal working, and in the "foundries, heat pressing,
      forging, and rolling mills" sector. A significant excess of miscarriages was
      present only in women working in commerce. DISCUSSION: The results demonstrated
      overall a low consistency compared with those obtained via other surveillance
      systems of occupational morbidity and mortality, as well as by means of
      analytical studies. The results appear more plausible for the sectors
      characterized by a low number of job tasks, or by a more homogenous exposure to
      risk factors among workers in different jobs. Among the limitations of this study
      the lack of a complete occupational history, the absence of information on
      potential confounders like smoking and alcohol consumption, and the probable non
      differential misclassification of the longest held job need to be stressed

PMID- 15871627
TI  - [About job classifications].
AB  - BACKGROUND: In the various existing information systems, the work-related
      variables (occupation, job position, and economic sector) are not always
      classified in the same manner. OBJECTIVES: To develop a classification of
      occupations and economic sectors that could be used for the majority of analyses
      of data on work-related morbidity and mortality. METHODS: The classification of
      occupations was created with the following criteria in mind: comparability with
      the currently used classification systems ISTAT (the National Institute of
      Statistics) 1971, 1981, 1991 and INAIL (the National Institute for Insurance
      Against Accidents & Diseases); a limited number of items, so as to ensure
      acceptable statistical power; maximum variance among groups and minimum variance
      within groups, in terms of the three dimensions of greatest interest for defining
      exhausting jobs. To this end, three groups of experts were consulted, one group
      of experts in the analysis of occupational differences in the occurrence of
      accidents and two groups of experts on occupational health. RESULTS: The three
      different sets of aggregates produced by the three groups of experts were
      combined into 56 items, referred to as the "Classification of occupations for the
      surveillance of differences in mortality and morbidity". CONCLUSIONS: The
      classification can be used in future analyses of occupational risks and injuries
      for the comparison of different information sources and time periods.

PMID- 15871628
TI  - Anthracycline-induced cardiotoxicity in children with cancer: strategies for
      prevention and management.
AB  - The fact that anthracyclines are cardiotoxic seriously narrows their therapeutic
      index in cancer therapy. The cardiotoxic risk increases with the cumulative dose
      and may lead to congestive heart failure (CHF) and dilated cardiomyopathy in
      adults and in children. The prevention of anthracycline-induced cardiotoxicity is
      particularly important in children who can be expected to survive for decades
      after being cured of their malignancy. Attempts to reduce anthracycline
      cardiotoxicity have been directed towards: (i) decreasing myocardial
      concentrations of anthracyclines and their metabolites by dose limitation and
      schedule modification; (ii) developing less cardio-toxic analogs; and (iii)
      concurrently administering cardioprotective agents to attenuate the effects of
      anthracyclines on the heart. As regards schedule modification, avoidance of
      anthracycline peak levels may reduce the pathologic and clinical cardiotoxicity,
      although this has not always been observed. The analogs of doxorubicin, such as
      idarubicin and epirubicin, have similar cardiotoxicity to that of doxorubicin
      when given in amounts of equivalent myelotoxicity. Liposomal anthracyclines are a
      new class of agents that may permit more specific organ targeting, thereby
      producing less systemic and cardiac toxicity, but more studies are required to
      assess the advantages, if any, of these preparations over classical
      anthracyclines. The cardioprotective agent, dexrazoxane, an iron chelator, is
      highly effective and provides short-term cardioprotection to most patients
      receiving even the most intensive doxorubicin-containing regimens. Its long-term
      benefits remain to be determined. In addition, data remain insufficient to make
      specific recommendations regarding current use of dexrazoxane in children. It is
      thought that subtle abnormalities, related to anthracycline treatment in
      childhood, can develop into more permanent myocardial disease resulting in
      cardiomyopathy, which may progress to CHF. As regards the therapy of patients
      with anthracycline cardiotoxicity, two different situations have, therefore, to
      be considered: (i) if the patient presents with cardiac abnormalities, such as a
      reduction in fractional shortening at echocardiogram, without cardiac symptoms;
      and (ii) if the patient has CHF. In the presence of CHF, recovery with digitalis
      diuretic therapy alone seldom occurs, and in patients who have refractory
      hemodynamic decompensation, heart transplantation is indicated. In patients with
      CHF, therapy with ACE inhibitors induces improvement in left ventricular
      structure and function, but this improvement is transient. Randomized clinical
      trials are, therefore, necessary to determine the effects of ACE inhibitors in
      mild-to-moderate left ventricular dysfunction. The beneficial effects of beta
      adrenoceptor antagonists (beta-blockers) on cardiac function in heart failure due
      to anthracyclines seem comparable with those observed in other forms of heart
      failure with systolic dysfunction. Many drugs are available to treat children
      with CHF due to anthracycline treatment, but they are only palliative.

PMID- 15871630
TI  - Neonatal chlamydial infections: prevention and treatment.
AB  - Neonatal chlamydial infection, which manifests principally as ophthalmia
      neonatorum (ON) or pneumonia, is a significant cause of neonatal morbidity.
      Widespread use of silver nitrate drops resulted in a dramatic decline in the
      incidence of gonococcal ophthalmia but had much less impact on the incidence of
      neonatal chlamydial infection. Chlamydia trachomatis has become the most common
      infectious cause of ON in developed countries.A number of prophylactic antibiotic
      or antiseptic agents have been used to prevent ON. Prophylaxis with 1% silver
      nitrate ophthalmic drops, 0.5% erythromycin ophthalmic ointment, or 1%
      tetracycline ointment has comparable efficacy for the prevention of chlamydial
      ophthalmia but does not offer protection against nasopharyngeal colonization or
      the development of pneumonia. Erythromycin or tetracycline topically have been
      used as prophylactic agents because of their allegedly superior activity for the
      prevention of ON and because they produced less chemical conjunctivitis compared
      with silver nitrate. However, the relative efficacy of these agents for
      chlamydial infection and the emergence of beta-lactamase-producing Neisseria
      gonorrheae has raised questions regarding their effectiveness when applied
      topically for prophylaxis of ON. Compared with these agents, a 2.5% povidone
      iodine ophthalmic solution has been found to have greater efficacy for the
      prevention of ON generally, and chlamydial ophthalmia specifically. In countries
      where the incidence of ON is very low, an alternative strategy is to institute
      prenatal screening and treatment of infected mothers, forgo routine neonatal
      prophylaxis, and follow-up infants after birth for the possible development of
      infection. For the treatment of chlamydial ophthalmia or pneumonia, oral
      erythromycin for 2 weeks is recommended; additional topical therapy is
      unnecessary. However, in approximately 20-30% of infants, therapy will not
      eradicate the organism and the infant may require a repeat oral course of
      antibiotics. The few published studies on the use of the new oral macrolide
      antibiotics, such as azithromycin, roxithromycin, or clarithromycin for
      chlamydial infections in neonates suggest that these agents may be effective;
      however, more data on their tolerability and efficacy in this patient group are
      warranted.

PMID- 15871631
TI  - Use of probiotics in children with acute diarrhea.
AB  - Probiotics, defined as microbial cell preparations or components of microbial
      cells that have a beneficial effect on the health and well being of the host,
      have traditionally been used to treat and prevent a variety of infections.
      Beneficial effects of probiotics in acute infectious diarrhea in children seem to
      be: (i) moderate; (ii) strain-dependent; (iii) dose dependent; (iv) significant
      in watery diarrhea and viral gastroenteritis, but non-existent in invasive,
      bacterial diarrhea; and (v) more evident when treatment with probiotics is
      initiated early in the course of disease. Three large, randomized controlled
      trials (RCTs) provide evidence of a very modest effect (statistically
      significant, but of questionable clinical importance) of some probiotic strains
      (Lactobaccillus GG, Lactobaccillus reuteri, Bifodobacterium lactis) on the
      prevention of community-acquired diarrhea. We have found conflicting evidence
      from four RCTs on the efficacy of Lactobacillus GG and B. bifidum and
      Streptococcus thermophilus in the prevention of nosocomial diarrhea in children.
      Two RCTs in children provide evidence of a moderate beneficial effect of
      Lactobacillus GG in the prevention of antibacterial-associated diarrhea (AAD),
      but results in adults are conflicting. Data on the efficacy of other probiotic
      strains in AAD in children are very limited. In conclusion, to date, the most
      extensively studied and best documented clinical application of probiotics in
      children is for the treatment of acute watery diarrhea of rotaviral or presumably
      viral etiology. Studies documenting effects in other types of diarrheal diseases
      in children are limited, although some preliminary results are promising. The
      effects of different probiotic microorganisms are not equal. Only very few
      probiotic strains have been tested rigorously in RCTs. Many questions remain to
      be answered. Future clinical trials should evaluate carefully selected, precisely
      defined probiotic strains and address clinically important endpoints.

PMID- 15871632
TI  - Economic evaluation of an extended acellular pertussis vaccine program for
      adolescents in Quebec, Canada.
AB  - OBJECTIVE: Pertussis is a frequent cause of cough illness in adolescents. In
      Canada, immunization against pertussis in public programs has been restricted to
      children under 7 years of age. The purpose of this analysis was to estimate the
      health and economic impact of an additional booster dose of the acellular vaccine
      in adolescents in Quebec. METHOD: We performed a cost-effectiveness analysis,
      based on a predictive spreadsheet dynamic model following a cohort of 90,929
      adolescents in Quebec from the age of 14 years over a 10-year period from the
      Quebec Ministry of Health (MOH) and societal (SOC) perspectives. The model was
      used to compare costs (2003 values) and benefits of an adolescent vaccination
      program (AVP), including a diptheria, tetanus, and acellular pertussis (dTacp)
      vaccine administered at age 14 years, with current practice. RESULTS: From the
      MOH perspective, a booster vaccination of dTacp at age 14 years via the AVP would
      produce a yearly additional expected cost of Can dollars 1.06 per adolescent with
      an incremental cost-effectiveness ratio (ICER) of Can dollars 480 per pertussis
      case avoided based on a 10-year period. When outcomes are discounted at 3%, the
      ICER rises to Can dollars 527 per discounted pertussis case avoided. From the SOC
      perspective, the AVP would cost Can dollars 0.83 per adolescent per year with an
      additional cost per avoided pertussis case of Can dollars 377 (Can dollars 414
      per additional discounted case of pertussis avoided). Over the 10-year period,
      2012 non-discounted cases of pertussis would be prevented with approximately two
      hospital admissions averted. CONCLUSION: This study suggests that administering a
      booster dose of dTacp at age 14 years to replace the diptheria and tetanus
      vaccination will slightly increase the economic burden from MOH and SOC
      perspectives; however, the number of pertussis cases and the number of hospital
      admissions will decrease.

PMID- 15871629
TI  - Staphylococcal skin infections in children: rational drug therapy
      recommendations.
AB  - Staphylococcus aureus remains one of the most common and troublesome of bacteria
      causing disease in humans, despite the development of effective antibacterials
      and improvement in hygiene. The organism is responsible for over 70% of all skin
      and soft tissue infections in children and accounts for up to one-fifth of all
      visits to pediatric clinics. Skin and soft tissue infections that are
      predominantly caused by S. aureus include bullous and non-bullous impetigo,
      folliculitis, furunculosis, carbunculosis, cellulitis, surgical and traumatic
      wound infections, mastitis, and neonatal omphalitis. Other skin and soft tissue
      infections may also be caused by S. aureus but are often polymicrobial in origin
      and require special consideration. These include burns, decubitus ulcers
      (particularly in the perianal region), puncture wounds of the foot, as well as
      human and mammalian bites. Treatment of staphylococcal skin infections varies
      from topical antiseptics to prolonged intravenous antibacterials, depending on
      severity of the lesions and the health of the child. The treatment of choice for
      oral antibacterials remains the penicillinase-resistant penicillins such as
      flucloxacillin. Cefalexin and erythromycin are suitable cost-effective
      alternatives with broader cover, although care must be taken with the use of
      macrolides because of development of resistance to multiple families of
      antibacterials, particularly the lincosamides. Other cephalosporins such as
      cefadroxil and cefprozil are also effective, can be given once daily and have a
      better tolerability profile -- while azithromycin has a further advantage of a 3
      day course. However, all of these agents are more expensive. Although the
      antibacterials have been given for 10 days in most clinical trials, there is no
      evidence that this duration is more effective than a 7-day course. In children
      requiring intravenous therapy, ceftriaxone has a major advantage over other
      antibacterials such as sulbactam/ampicillin and cefuroxime in that it can be
      given once daily and may, therefore, be suitable for outpatient treatment of
      moderate-to-severe skin infections. Newer-generation cephalosporins and
      loracarbef are also effective and have a broader spectrum of activity, but do not
      offer any added benefit and are significantly more expensive. Skin and soft
      tissue infections due to methicillin-resistant S. aureus (MRSA) are still
      relatively uncommon in children. Well children with community-acquired MRSA
      infections can be treated with clindamycin or trimethoprim-sulfamethoxazole
      (cotrimoxazole), but must be observed closely for potentially severe adverse
      effects. In severe infections, vancomycin remains the treatment of choice, while
      intravenous teicoplanin and clindamycin are suitable alternatives. Linezolid and
      quinupristin/dalfopristin are currently showing great promise for the treatment
      of multi-resistant Gram-positive infections. While the choice of antibacterial is
      important, supportive management, including removal of any infected foreign
      bodies, surgical drainage of walled-off lesions, and regular wound cleaning, play
      a vital role in ensuring cure.

PMID- 15871635
TI  - Pharmacokinetic profile of ganciclovir after its oral administration and from its
      prodrug, valganciclovir, in solid organ transplant recipients.
AB  - BACKGROUND: Valganciclovir (Valcyte) has recently been approved for the
      prevention of cytomegalovirus (CMV) disease in high-risk (CMV donor positive
      [D+]/recipient negative [R-]) solid organ transplant (SOT) recipients. Large
      scale studies describing the pharmacokinetics of valganciclovir in SOT recipients
      are lacking. A recent randomised, double-blind study of valganciclovir in 364
      D+/R- (intent-to-treat population) SOT recipients provided valuable data on which
      a population pharmacokinetic analysis was performed. METHODS: The
      pharmacokinetics of ganciclovir from oral ganciclovir (Cymevene, 1000 mg three
      times daily) and from valganciclovir (900 mg once daily) were described with
      plasma levels from 240 patients (1181 datapoints describing 449 pharmacokinetic
      profiles) using nonlinear mixed-effects modelling (NONMEM) software. A two
      compartment pharmacokinetic model with separate absorption/metabolism and
      absorption parameters for valganciclovir and ganciclovir, respectively, was
      developed. RESULTS: Exposure to ganciclovir from valganciclovir averaged 1.65
      fold greater than that from oral ganciclovir (95% CI 1.58, 1.81); respective
      daily area under the plasma concentration-time curve values were 46.3 +/- 15.2
      microg . h/mL and 28.0 +/- 10.9 microg . h/mL. The relative systemic exposure of
      ganciclovir was approximately 8-fold higher from valganciclovir than oral
      ganciclovir. Exposure to ganciclovir from valganciclovir was similar among liver,
      heart and kidney transplant recipients (46.0 +/- 16.1, 40.2 +/- 11.8 and 48.2 +/-
      14.6 microg . h/ mL, respectively). Adherence to the prescribed dosing regimens,
      which were reduced for renal impairment, gave consistent exposure to ganciclovir.
      CONCLUSION: Oral valganciclovir produces exposures of ganciclovir exceeding those
      attained with oral ganciclovir, but in line with those reported after standard
      intravenous administration of ganciclovir. This indicates that oral
      valganciclovir is suitable in circumstances requiring prophylactic use of
      ganciclovir and allows for more convenient management of patients at risk of CMV
      disease.

PMID- 15871633
TI  - Pharmacokinetics of proton pump inhibitors in children.
AB  - The use of proton pump inhibitors (PPIs) has become widespread in children and
      infants for the management of paediatric acid-related disease. Pharmacokinetic
      profiles of only omeprazole and lansoprazole have been well characterised in
      children over 2 years of age with acid-related diseases. Few data have been
      recently published regarding the pharmacokinetics of pantoprazole in children,
      and none are available for rabeprazole or esomeprazole. The metabolism of PPI
      enantiomers has never been studied in the paediatric population. A one
      compartment model best describes the pharmacokinetic behaviour of omeprazole,
      lansoprazole and pantoprazole in children, with important interindividual
      variability for each pharmacokinetic parameter. Like adults, PPIs are rapidly
      absorbed in children following oral administration; the mean time to reach
      maximum plasma concentration varies from 1 to 3 hours. Since these agents are
      acid labile, their oral formulations consist of capsules containing enteric
      coated granules. No liquid formulation is available for any of the PPIs. Thus,
      for those patients unable to swallow capsules, extemporaneous liquid preparations
      for omeprazole and lansoprazole have been reported; however, neither the absolute
      nor the relative bioavailabilities of these oral formulations have been studied
      in children. Intravenous formulations are available for omeprazole (in Europe),
      lansoprazole and pantoprazole. PPIs are rapidly metabolised in children, with
      short elimination half-lives of around 1 hour, similar to that reported for
      adults. All PPIs are extensively metabolised by the liver, primarily by
      cytochrome P450 (CYP) isoforms CYP2C19 and CYP3A4, to inactive metabolites, with
      little unchanged drug excreted in the urine. Similar to that seen in adults, the
      absolute bioavailability of omeprazole increases with repeated dosing in
      children; this phenomenon is thought to be due to a combination of decreased
      first-pass elimination and reduced systemic clearance. The apparent clearance
      (CL/F) of omeprazole, lansoprazole and pantoprazole appears to be faster for
      children than for adults. A higher metabolic capacity in children as well as
      differences in the extent of PPI bioavailability are most likely responsible for
      this finding. This may partly account for the need in children for variable and
      sometimes considerably greater doses of PPIs, on a per kilogram basis, than for
      adults to achieve similar plasma concentrations. Furthermore, no studies have
      been able to demonstrate a statistically significant correlation between age and
      pharmacokinetic parameters among children. Despite the small number of very young
      infants studied, there is some evidence for reduced PPI metabolism in newborns.
      The limited paediatric data regarding the impact of CYP2C19 genetic polymorphism
      on PPI metabolism are similar to those reported for adults, with poor
      metabolisers having 6- to 10-fold higher area under the concentration-time curve
      values compared with extensive metabolisers. Finally, because a
      pharmacokinetic/pharmacodynamic relationship exists for PPIs, the significant
      interindividual variability in their disposition may partly explain the wide
      range of therapeutic doses used in children. Further studies are needed to better
      define the pharmacokinetics of PPIs in children <2 years of age.

PMID- 15871636
TI  - No effect of renal function or dialysis on pharmacokinetics of cinacalcet
      (Sensipar/Mimpara).
AB  - OBJECTIVE: Cinacalcet (cinacalcet HCl; Sensipar/Mimpara) is a calcimimetic that
      is a treatment for secondary hyperparathyroidism in patients with renal failure.
      The objective of this study was to assess the effects of renal function and
      dialysis on the pharmacokinetics and pharmacodynamics of cinacalcet. METHODS: Two
      open-label, single-dose (75 mg) studies of cinacalcet were performed: study 1
      examined 36 subjects who had renal function ranging from normal to requiring
      haemodialysis, and study 2 examined ten subjects who were receiving continuous
      ambulatory peritoneal dialysis. Cinacalcet plasma concentrations were determined
      using a liquid chromatography-mass spectrometry/mass spectrometry assay.
      Cinacalcet pharmacokinetics were assessed using noncompartmental analyses.
      RESULTS: Following single-dose administration of cinacalcet, there was no
      evidence of increasing exposure with increasing degree of renal impairment, and
      the pharmacokinetic profile was similar for all subjects regardless of whether
      they were receiving haemodialysis (no difference on dialysis or nondialysis days
      detected) or peritoneal dialysis. Protein binding of cinacalcet, determined in
      study 1 only, was similar in all groups and the level of renal function did not
      affect the pharmacodynamics (as determined by intact parathyroid hormone and
      calcium levels). No serious adverse events occurred during either study.
      CONCLUSION: The degree of renal impairment and mode of dialysis do not affect the
      pharmacokinetics or pharmacodynamics of cinacalcet. Therefore, the dose of
      cinacalcet does not need to be altered for degree of renal impairment or dialysis
      modality.

PMID- 15871634
TI  - Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions.
AB  - Ezetimibe is the first lipid-lowering drug that inhibits intestinal uptake of
      dietary and biliary cholesterol without affecting the absorption of fat-soluble
      nutrients. Following oral administration, ezetimibe is rapidly absorbed and
      extensively metabolised (>80%) to the pharmacologically active ezetimibe
      glucuronide. Total ezetimibe (sum of 'parent' ezetimibe plus ezetimibe
      glucuronide) concentrations reach a maximum 1-2 hours post-administration,
      followed by enterohepatic recycling and slow elimination. The estimated terminal
      half-life of ezetimibe and ezetimibe-glucuronide is approximately 22 hours.
      Consistent with the elimination half-life of ezetimibe, an approximate 2-fold
      accumulation is observed upon repeated once-daily administration. The recommended
      dose of ezetimibe 10 mg/day can be administered in the morning or evening without
      regard to food. There are no clinically significant effects of age, sex or race
      on ezetimibe pharmacokinetics and no dosage adjustment is necessary in patients
      with mild hepatic impairment or mild-to-severe renal insufficiency. The major
      metabolic pathway for ezetimibe consists of glucuronidation of the 4
      hydroxyphenyl group by uridine 5'-diphosphate-glucuronosyltransferase isoenzymes
      to form ezetimibe-glucuronide in the intestine and liver. Approximately 78% of
      the dose is excreted in the faeces predominantly as ezetimibe, with the balance
      found in the urine mainly as ezetimibe-glucuronide. Overall, ezetimibe has a
      favourable drug-drug interaction profile, as evidenced by the lack of clinically
      relevant interactions between ezetimibe and a variety of drugs commonly used in
      patients with hypercholesterolaemia. Ezetimibe does not have significant effects
      on plasma levels of HMG-CoA reductase inhibitors commonly known as statins
      (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin,
      simvastatin), fibric acid derivatives (gemfibrozil, fenofibrate), digoxin,
      glipizide, warfarin and triphasic oral contraceptives (ethinylestradiol and
      levonorgestrel). Concomitant administration of food, antacids, cimetidine or
      statins had no significant effect on ezetimibe bioavailability. Although
      coadministration with gemfibrozil and fenofibrate increased the bioavailability
      of ezetimibe, the clinical significance is thought to be minor considering the
      relatively flat dose-response curve of ezetimibe and the lack of dose-related
      increase in adverse events. In contrast, coadministration with the bile acid
      binding agent colestyramine significantly decreased ezetimibe oral
      bioavailability (based on area under the plasma concentration-time curve of total
      ezetimibe). Hence, ezetimibe and colestyramine should be administered several
      hours apart to avoid attenuating the efficacy of ezetimibe. Finally, higher
      ezetimibe exposures were observed in patients receiving concomitant ciclosporin,
      and ezetimibe caused a small but statistically significant effect on plasma
      levels of ciclosporin. Because treatment experience in patients receiving
      ciclosporin is limited, physicians are advised to exercise caution when
      initiating ezetimibe in the setting of ciclosporin coadministration, and to
      carefully monitor ciclosporin levels.

PMID- 15871637
TI  - Lack of pharmacokinetic interactions between steady-state zonisamide and valproic
      acid in patients with epilepsy.
AB  - OBJECTIVES: This study evaluated the effect of the addition of zonisamide on
      valproic acid (valproate sodium) pharmacokinetics under steady-state conditions
      in patients with epilepsy. A second aim was to characterise zonisamide
      pharmacokinetics in the presence of valproic acid. METHODS: Twenty-two patients
      (males and females, 18-55 years of age) with their seizure disorder stabilised on
      valproic acid monotherapy were included in a two-centre, open-label, one-way drug
      interaction trial. The zonisamide dose was gradually increased from 100 mg/day to
      400 mg/day. Three pharmacokinetic profiles were obtained: on days -7 and -1, to
      assess pharmacokinetic parameters of oral valproic acid administered alone, and
      on day 35, after 14 days of zonisamide treatment at the maximal tolerated dose,
      to evaluate the effect of zonisamide on valproic acid pharmacokinetics and to
      characterise zonisamide pharmacokinetics in the presence of valproic acid.
      RESULTS: Seventeen patients completed the study, with 16 patients contributing to
      the pharmacokinetic analyses. Coadministration of zonisamide and valproic acid
      appeared reasonably well tolerated. Steady-state dosing of zonisamide (200mg
      twice daily) had no statistically significant effect on the mean (+/- SD) maximum
      observed plasma concentration (C(max)) [70.8 +/- 20.5 vs 69.2 +/- 27.0
      microg/mL], area under the plasma concentration-time curve from the time of
      dosing to 12 hours post-dose (AUC(12)) [689.3 +/- 250.4 vs 661.8 +/- 251.3 microg
      . h/mL] or other evaluated pharmacokinetic parameters for valproic acid measured
      before and after zonisamide administration. Furthermore, 90% confidence intervals
      for the ratio of the geometric means (day 35/day -1) of valproic acid
      pharmacokinetic exposure measures fell only slightly outside the 'no effect'
      range of 0.80-1.25. In the presence of valproic acid, mean zonisamide oral
      clearance (1.23 L/h) and elimination half-life (52.5 hours) are generally
      consistent with values reported for healthy volunteers receiving zonisamide
      monotherapy. CONCLUSION: There is no apparent clinically significant effect of
      steady-state dosing of zonisamide on valproic acid pharmacokinetics, and valproic
      acid did not appear to affect the pharmacokinetics of zonisamide, indicating that
      no dosage adjustment of either drug should be required when they are used in
      combination in patients with epilepsy.

PMID- 15871638
TI  - Pharmacokinetics and pharmacodynamics of low dose mycophenolate mofetil in HIV
      infected patients treated with abacavir, efavirenz and nelfinavir.
AB  - BACKGROUND: The use of mycophenolate mofetil in combination with highly active
      antiretroviral therapy (HAART) has been proposed in order to inhibit HIV
      replication. Due to the low doses involved, pharmacokinetic-pharmacodynamic
      monitoring is recommended. OBJECTIVE: The aim of this study was to characterise
      the pharmacokinetic and pharmacodynamic monitoring of low doses of mycophenolate
      mofetil (0.25 g twice daily) in HIV-infected patients treated with HAART and
      after programmed discontinuation of HAART, in order to assess whether low doses
      of this immunosuppressive agent provide a biological effect. METHODS:
      Mycophenolic acid (MPA) plasma levels (assessed by high-performance liquid
      chromatography) and the capacity of patients' sera to inhibit CEM cell line
      proliferation (assessed by (3)H-thymidine uptake) were measured post-dose at 0,
      20, 40 minutes and 1, 2, 4, 6, 8, 10 and 12 hours in nine HIV-infected patients
      treated with a combination of abacavir, nelfinavir and efavirenz (HAART) and
      mycophenolate mofetil 0.25 g twice daily at days 7, 28, 120 and 150 (30 days
      without HAART) after the treatment initiation. A control group of eight patients
      was treated with HAART alone. RESULTS: In the 35 post-dose curves analysed, no
      differences were found in MPA levels between days 7, 28, 120 and 150: area under
      the plasma concentration-time curve - mean value 15.3 mg . h/L, range 10.4-24.4
      mg . h/L; minimum plasma concentration - mean value 0.60 mg/L, range 0.20-4.67
      mg/L; maximum plasma concentration mean value 2.60 mg/L, range 0.94-7.98 mg/L.
      Pretreatment patients' sera did not inhibit CEM proliferation. Post-treatment
      patients' sera inhibited CEM proliferation to <40% in 25 of 35 curves at 0 hours
      (six of nine patients), in 34 of 35 curves at 1 hour, in 32 of 35 curves at 2
      hours, in 22 of 35 curves at 4 hours, and in 8 of 35 curves at 12 hours. The MPA
      level versus CEM proliferation inhibition had a concentration that produces 50%
      of the maximum drug effect (EC(50)) of 0.33 mg/L. Viral load at day 150 was >200
      copies/mL in all control patients and in three of nine patients receiving
      mycophenolate mofetil. These three patients were the only ones repeatedly unable
      to inhibit pre-dose CEM proliferation to <40%. CONCLUSIONS: Mycophenolate mofetil
      pharmacokinetic profiles in HIV patients under HAART are not significantly
      different from those found in transplant patients. Sera from the majority of
      patients receiving low doses of mycophenolate mofetil inhibited lymphocyte
      proliferation during most of the inter-dose interval, despite low MPA plasma
      levels. For some patients, higher doses may be necessary: the capacity of sera to
      inhibit CEM proliferation may help to identify these patients.

PMID- 15871639
TI  - Pharmacokinetic evaluation of meropenem and imipenem in critically ill patients
      with sepsis.
AB  - OBJECTIVE: To evaluate and compare the pharmacokinetic profiles of imipenem and
      meropenem in a population of critically ill patients with sepsis to find possible
      differences that may help in selecting the most appropriate drug and/or dosage in
      order to optimise empiric antimicrobial therapy. PATIENTS AND METHODS: This was a
      single-centre, randomised, nonblind study of the pharmacokinetics of both
      intravenous imipenem 1g and meropenem 1g in 20 patients admitted to an intensive
      care unit with sepsis in whom antimicrobial therapy was indicated on clinical
      grounds. Patients were divided into two groups: group I received intravenous
      imipenem 1g plus cilastatin 1g, and group II received intravenous meropenem 1g
      over 30 minutes. Peripheral blood samples were collected at 0, 0.5 (end of
      infusion), 0.75, 1, 1.5, 2, 3, 4, 6 and 8 hours after the first dose and were
      centrifuged for 10 minutes at 4 masculineC. Urine samples were collected during
      the 8 hours after antimicrobial administration at 2-hour intervals: 0-2, 2-4, 4-6
      and 6-8 hours. The total volume of urine was recorded; the serum and urine
      samples were immediately frozen and stored at -80 masculineC until assayed.
      Pharmacokinetic analysis was carried out through computerised programs using the
      least-square regression method and a two-compartment open model. Statistical
      differences were evaluated by means of one-way ANOVA. RESULTS: The following
      pharmacokinetic differences between the two drugs were observed: the imipenem
      mean peak serum concentration was significantly higher than for meropenem (90.1
      +/- 50.9 vs 46.6 +/- 14.6 mg/L, p < 0.01); the area under the serum concentration
      time curve was significantly higher for imipenem than for meropenem (216.5 +/-
      86.3 vs 99.5 +/- 23.9 mg . h/L, p < 0.01), while the mean volume of distribution
      and mean total clearance were significantly higher for meropenem than for
      imipenem (25 +/- 4.1 vs 17.4 +/- 4.5L, p < 0.01 and 191 +/- 52.2 vs 116.4 +/-
      42.3 mL/min, p < 0.01, respectively). CONCLUSION: The more favourable
      pharmacokinetic profile of imipenem compared with meropenem in critically ill
      patients with sepsis might balance the possibly greater potency demonstrated in
      vitro for meropenem against Gram-negative strains. Hence, the clinical efficacy
      of the two carbapenems depends mostly on their correct dosage.

PMID- 15871640
TI  - Total first-year costs of acute coronary syndrome in a managed care setting.
AB  - OBJECTIVE: There is a limited amount of literature examining the burden and cost
      of illness of acute coronary syndrome (ACS) in the managed care population. The
      goal of this study was to estimate the total cost of health care utilization
      (health plan plus patient) in the 12-month period following newly onset ACS. The
      demographic and health characteristics of these patients are compared with the
      similar data from 2 large clinical trials: CURE (Clopidogrel in Unstable Angina
      to Prevent Recurrent Events) and PROVE IT-TIMI 22 (Pravastatin or Atorvastatin
      Evaluation and Infection Therapy--Thrombolysis in Myocardial Infarction 22).
      METHODS: A retrospective claims analysis was conducted for the 2-year period from
      July 1, 1999, through June 30, 2001. ACS was defined as an emergency room visit
      or hospitalization with a primary International Classification of Diseases, 9th
      Edition/Revision (ICD-9) diagnosis of 410.xx (acute myocardial infarction) or
      411.1x (intermediate coronary syndrome). Patients were required to be free of any
      ACS claim in the previous 6 months. Patients without 6 months of prior continuous
      enrollment or those patients younger than 18 years were excluded. Patients were
      followed up to 12 months to identify total medical and pharmacy costs,
      revascularization procedures, and medication use. RESULTS: A total of 13,731
      patients met the inclusion criteria, yielding 133,814 months of follow-up (mean:
      9.75 months per patient) and representing approximately 0.4% of the managed care
      members in the database during the study period. The mean age was 54 years and
      68% were male. The total direct cost incurred by the health plan and patients was
      dollar 309 million (dollar 2,312 per patient-month of follow-up); 72% of total
      costs were attributable to hospitalizations. The majority of costs were medical
      (dollar 286 million, 93%), and dollar 23 million (7%) were pharmacy costs. Fifty
      one percent of patients had a revascularization procedure, which was typically
      performed during the index hospitalization (median time to revascularization was
      0 days). Coronary artery stent implantation was the most common revascularization
      procedure (68%). During follow-up, 490 patients (3.6%) had a detectable death,
      58% of patients received a beta-blocker, 60% received one or more cholesterol
      lowering medications, and 36% of patients received clopidogrel therapy. Aspirin
      therapy was not measured. CONCLUSIONS: These managed-care patients with newly
      onset ACS incurred substantial costs in the 12 months following initial
      presentation. Revascularization was a common therapeutic intervention for these
      patients. There appear to be opportunities to improve medication therapy after an
      acute ACS event. There were some demographic and health characteristics that were
      different in these commercially insured patients from those in 2 large clinical
      trials.

PMID- 15871641
TI  - The cost of falls among the community-dwelling elderly.
AB  - OBJECTIVE: To estimate the direct medical costs of falls in the population of
      community-dwelling elderly. METHODS: Data from a sample of 4,025 consumers from
      the 1997 Medical Expenditure Panel Survey were used to make estimates that were
      representative of the population of civilian, noninstitutionalized elderly in the
      United States. RESULTS: In 1997, 9% of the noninstitutionalized elderly
      population of the United States reported medical conditions related to falls. The
      estimated total direct medical cost of these conditions was dollar 6.2 billion in
      1997 dollars and dollar 7.8 billion in 2002 dollars. The mean cost per person who
      had fallen was dollar 2,039 in 1997 dollars and dollar 2,591 in 2002 dollars.
      Inpatient hospitalizations accounted for 65% of total costs, followed by office
      based medical visits and home health care, each accounting for about 10% of total
      direct medical costs, and hospital outpatient visits for 7.6%. About 78% of fall
      related costs were reimbursed by Medicare. CONCLUSION: Fall-related medical
      conditions affect a substantial number of the community-dwelling elderly and
      result in direct medical costs of dollar 6 to dollar 8 billion per year in the
      United States. The total economic burden of falls is significantly higher because
      this estimate does not include direct nonmedical, intangible, and indirect costs.
      The results of this study highlight the importance of research aimed at
      decreasing the incidence and severity of falls in the elderly.

PMID- 15871642
TI  - Cost-effectiveness analysis of ondansetron and prochlorperazine for the
      prevention of postoperative nausea and vomiting.
AB  - OBJECTIVE: To compare the cost-effectiveness of 2 antiemetic agents, ondansetron
      and prochlorperazine, for the prevention of postoperative nausea and vomiting
      (PONV) in patients undergoing total hip replacement or total knee replacement
      procedures. METHODS: The cost-effectiveness analysis model was applied to data
      derived from a previous clinical study conducted in 1995 and 1996. This study
      involved 78 adult patients (62.8% female and 37.2% male) undergoing total hip
      replacement or total knee replacement procedures. Patients were enrolled in a
      randomized, double-blind manner to receive either ondansetron 4 mg intrvenously
      (n=37) or prochlorperazine 10 mg intramuscularly (n=41) immediately upon
      completion of surgery and were monitored for occurrences of PONV during the
      subsequent 48 hours. In our analysis, we measured the cost-effectiveness ratio
      (C/E ratio), defined as the cost per successfully treated patient, for each
      antiemetic agent using the clinical data obtained from the previous study.
      RESULTS: The incidence of PONV and use of rescue antiemetics was significantly
      greater in the ondansetron group compared with the prochlorperazine group. The
      mean total costs of PONV management per patient in the prochlorperazine and
      ondansetron groups were dollar 13.99 and dollar 51.98, respectively (based on
      2004 average wholesale prices [AWP]). The cost of successfully treating one
      patient with prochlorperazine and ondansetron was dollar 31.87 and dollar 275.01,
      respectively. One-way sensitivity analysis was performed adjusting the percent
      efficacy rate of each antiemetic and the drug cost of ondansetron (up to a 50%
      reduction in AWP). Prochlorperazine remained the dominant strategy across each
      scenario. CONCLUSION: The results indicate that prochlorperazine is a more cost
      effective antiemetic compared with ondansetron for the prevention of PONV in a
      mixed gender, adult inpatient population undergoing total joint arthroplasty.

PMID- 15871643
TI  - Twelve-month drug cost savings related to use of an electronic prescribing system
      with integrated decision support in primary care.
AB  - OBJECTIVE: We reported previously the results of a 6-month controlled trial in
      which the use of a commercially available electronic prescribing system with
      integrated clinical decision support and evidence-based message capability was
      associated with significantly lower primary care drug costs. The original study
      focused on new prescriptions, defined as claims for a medication that the patient
      had not received in the previous 12 months. The main objectives of this follow-up
      report were to (a) determine if the 6-month savings on new prescriptions were
      sustained during 12 months of follow-up, (b) evaluate the impact of the
      computerized decision support system (CDSS) on all pharmacy claims and per-member
      per-month (PMPM) expenditures, and (c) evaluate the prescribing behaviors within
      8 high-cost therapeutic categories that were frequently targeted by the
      electronic messages to prescribers to help verify that the drug cost savings were
      due to the recommendations in the electronic prescribing system. METHODS: Two
      database queries were performed to identify additional pharmacy claims data for
      all Network Health Plan patients who were cared for by the 38 primary care
      clinicians (32 physicians, 4 nurse practitioners, and 2 physician assistants)
      included in our original 6-month study. This follow-up analysis (a) identified
      all new prescription claims for the 2 groups of clinicians throughout the 12
      month follow-up period (June 2002 through May 2003) and (b) assessed all pharmacy
      claims during the same 12-month period to provide more complete savings estimates
      and to examine between-group differences in PMPM expenditures. RESULTS: During 12
      months of follow-up, clinicians using the electronic prescribing system continued
      to have lower prescription costs than the controls. Clinicians using the
      electronic prescribing system had average costs for 26,674 new prescriptions that
      were dollar 4.12 lower (95% confidence interval, dollar 1.53-dollar 6.71;
      P=0.003) and PMPM expenditures that were dollar 0.57 lower than expected based on
      the changes observed for 24,507 new prescriptions written by clinicians in the
      control group. The average drug cost savings on new prescriptions were dollar 482
      per prescriber per month (PPPM), based upon prescription cost and dollar 465 PPPM
      based upon PMPM analysis. When all pharmacy claims (156,429) were analyzed, the
      intervention group.s average prescription cost was dollar 2.57 lower and their
      PMPM expenditures were dollar 1.07 lower than expected based on the changes
      observed in the control group. The average drug cost savings on all pharmacy
      claims were dollar 863 PPPM based on average prescription cost and dollar 873
      PPPM based on PMPM analysis. The proportion of prescriptions for highcost drugs
      that were the target of the CDSS messages to prescribers was a relative 17.5%
      lower among the intervention group (35.8%) compared with the control group
      (43.4%; P=0.03). CONCLUSIONS: An electronic prescribing system with integrated
      decision support shifted prescribing behavior away from high-cost therapies and
      significantly lowered prescription drug costs. The savings associated with
      altered prescribing behavior offset the monthly subscription cost of the system.

PMID- 15871644
TI  - The PRICE clinic for low-income elderly: a managed care model for implementing
      pharmacist-directed services.
AB  - OBJECTIVES: The Medicare Modernization Act of 2003 calls for medication therapy
      management programs (MTMPs) to control anticipated growth in drug use and
      expenditures. In 2006, prescription drug plan sponsors, including health plans,
      pharmacy benefit managers, and other entities, will be required to offer MTMP
      services performed by pharmacists or other health professionals. The Pharmacist
      Review to Increase Cost Effectiveness (PRICE) Clinic in Sacramento, California,
      is a pharmacist-directed, multidisciplinary model that is adaptable to providing
      MTMP services in a managed care setting. The PRICE Clinic serves a 3-fold
      mission: (1) to help low-income elderly patients decrease out-of-pocket (OOP)
      drug expenses; (2) to ensure that patients receive clinically appropriate, cost
      effective drug regimens; and (3) to improve access to needed medications. The
      objectives of this study were to characterize and document the number and type of
      PRICE clinic interventions; measure changes in generic drug use; document savings
      in OOP drug costs; and measure patient access to drugs that had been, or would
      have been, discontinued because of cost. METHODS: A noncontrolled retrospective
      PRICE Clinic database review was conducted for the 520 patients seen in the PRICE
      Clinic in calendar year 2002. Study participants were low-income elderly with
      multiple chronic diseases, multiple medications, and high drug costs. For each
      patient, researchers documented the number and type of interventions performed by
      pharmacists and the drug class involved in each intervention. Changes in generic
      drug use and OOP costs were assessed by a preanalysis and postanalysis of
      selected outcome variables and a comparison of results with comparable patient
      populations in large state and national databases. Self-report was used to
      examine whether patients had discontinued medications because of cost, and the
      PRICE Clinic database analysis examined whether interventions enabled patients to
      resume previously discontinued medications. RESULTS: PRICE clinic conducted 1,297
      interventions among the 520 study patients in 2002, an average of 2.5
      interventions per patient. The most common drug classes involved in interventions
      were lipid-lowering drugs, angiotensin-converting enzyme inhibitors, and asthma
      and allergy drugs. Generic drug use increased from 51% before PRICE clinic
      interventions to 56% afterward, a relative increase of 9.8% and more than 30%
      higher relative to the benchmark value. OOP medication expenditures decreased
      68%, from dollar 185 to dollar 60 per patient per month, or dollar 1,500 per
      patient per year. A total of 215 patients (41%) reported that they had or would
      soon discontinue drugs because of cost; 186 (87%) of these patients were able to
      continue or resume the drug as the result of PRICE Clinic interventions. The most
      common interventions were pharmaceutical industry-sponsored patient assistance
      programs, generic substitution, and therapeutic interchange. CONCLUSION: Results
      from this pilot study indicate the benefits of providing pharmacist-directed
      services to the population targeted by MTMP services, which encompasses Medicare
      beneficiaries with multiple chronic diseases, multiple drugs, and high drug
      costs. By providing pharmacist consultation at the point of care to ensure
      appropriate drug use, decrease OOP expenditures, and improve access to needed
      drugs, the PRICE Clinic is a possible model for further development in the
      implementation of MTMP services.

PMID- 15871645
TI  - ADHD: disease or social misfit?

PMID- 15871646
TI  - Appropriate econometric methods for pharmacoeconometric studies of retrospective
      claims data: an introductory guide.

PMID- 15871647
TI  - Prior authorization and the formulary exception process--examples from the real
      world.

PMID- 15871648
TI  - Medication therapy management programs--will patient need be satisfied?

PMID- 15871649
TI  - Clinical, service, and cost outcomes of computerized prescription order entry.

PMID- 15871650
TI  - Value for money in disease management of acute coronary syndrome--the price of
      aspirin to reduce the costs of ACS.

PMID- 15871651
TI  - The Academy of Managed Care Pharmacy's concepts in managed care pharmacy: prior
      authorization and the formulary exception process.

PMID- 15871652
TI  - Contractual incentives: a threat to evidence-based medicine?

PMID- 15871654
TI  - Evidence-based medicine: health care's next holy war.
AB  - OBJECTIVE: To review evidence-based medicine (EBM), how it emerged, how it works,
      and what drug utilization patterns across the United States would look like if we
      applied EBM methods to this population. SUMMARY: There is a collective
      presumption about the overuse of pharmaceuticals, unchallenged by any substantive
      data, that has become part of American folklore: high drug use by people in this
      country actually represents overuse. This presumption is completely unfounded. On
      the contrary, a recent analysis carried out by the RAND Corporation indicated
      that fewer than 70% of people in the United States with chronic illness receive
      adequate medical treatment. CONCLUSIONS: The flow of almost all medical research
      strongly supports the conclusion that more medicine is better. EBM has ably
      pointed out that too many patients receive unneeded diagnostic and surgical
      procedures. It will also demonstrate that too few patients receive appropriate
      medical care.

PMID- 15871655
TI  - The role of pharmacoeconomic modeling in evidence-based and value-based formulary
      guidelines.
AB  - OBJECTIVE: To review evidence-based medicine (EBM) in the context of
      pharmacoeconomic (PE) decision making by health care organizations. SUMMARY:
      Pharmacoeconomics involves processes similar to EBM, but it deals with decisions
      on the population rather than the patient level. The overall goal of PE is to
      provide the most efficient use of resources, taking into account both the cost
      and the value derived from a given technology. These evaluations assist health
      care decision making because both cost and effectiveness are considered. New
      therapies are increasingly complex in terms of administration, effects, and cost.
      As a result, PE models are likely to become more complex as well. At present,
      there is no standard threshold for what constitutes cost-effective therapy, so
      each organization is likely to have its own criterion for acceptance. CONCLUSION:
      Clinical trial results define the safety and efficacy of therapy but cannot
      determine whether a given technology represents a good buy for a specific
      organization. This requires PE analysis.

PMID- 15871656
TI  - Implementing community-based standards of care.
AB  - OBJECTIVE: To briefly review steps that should be followed in the progression
      from considering therapeutic options on the basis of evidence-based medicine
      (EBM) to implementing formulary decisions and clinical guidelines. SUMMARY:
      Results from EBM should guide selection of therapy for routine clinical practice.
      Pharmacists must spend considerable time carefully reviewing the designs and
      results of clinical trials and postmarketing information to develop accurate
      safety and efficacy profiles. The Pharmacy & Therapeutics (P&T) committee also
      requires pharmacoeconomic data for its deliberations, and that should include
      information about the economic, clinical, and humanistic value of new therapies.
      The P&T committee ultimately determines the business value of the new therapy
      based on the efficacy and safety profile derived from EBM, comparison with
      treatment alternatives, cost, provider needs, and system orientation. CONCLUSION:
      Proper accomplishment of all of these steps should result in adoption of
      efficacious, safe, and cost-effective therapies.

PMID- 15871661
TI  - IL-6 transsignaling: the in vivo consequences.
AB  - Cytokine receptors exist in membrane-bound and soluble forms. They bind their
      ligands with comparable affinity. Although most soluble receptors are antagonists
      because they compete with their membrane counterparts for their ligands, some
      soluble receptors are agonists. In this case, on target cells, the complex of
      cytokine and soluble cytokine receptor binds to a second receptor subunit and
      initiates intracellular signal transduction. The soluble receptors of the
      interleukin-6 (IL-6) family of cytokines--soluble IL-6 receptor (sIL-6R), sIL
      11R, and soluble ciliary neurotrophic factor receptor (sCNTFR)--are agonists. In
      vivo, the IL-6/sIL-6R complex stimulates several types of target cells not
      stimulated by IL-6 alone, as they do not express the membrane- bound IL-6R. This
      process has been named transsignaling. We have shown recently that in several
      chronic inflammatory diseases, such as chronic inflammatory bowl disease,
      peritonitis, and rheumatoid arthritis, as well as in colon cancer, transsignaling
      via the sIL-6R complexed to IL-6 is a crucial point in the maintenance of the
      disease. The mechanism by which the IL-6/sIL-6R complex regulates the
      inflammatory or neoplastic state is discussed.

PMID- 15871662
TI  - 17 Beta-estradiol improves survival in male mice with cardiomyopathy induced by
      cardiac-specific tumor necrosis factor-alpha overexpression.
AB  - A transgenic mouse model of congestive heart failure (CHF) consequent to cardiac
      specific overexpression of tumor necrosis factor-alpha (TNF-alpha) (TNF1.6)
      displays marked sex-related phenotypic differences. To clarify the potential
      contributions of estrogen to these sex-specific differences, male TNF1.6 mice
      were treated with 17beta- estradiol (E2). E2 treatment started at 25 +/- 1 days
      old (group A), but not at 36 +/- 2 days old (group B), significantly improved
      survival rate (p < 0.05). Furthermore, ventricular weight/body weight ratio was
      significantly decreased by E2 treatment in group A (p < 0.05). Echocardiography
      revealed that E2-treated hearts in group A exhibited less left ventricular
      dilatation (p < 0.05) relative to untreated male TNF1.6 mice (control). Moreover,
      in group A, E2 treatment partially reversed basal and isoproterenol-stimulated
      fractional shortening in TNF1.6 mice (p < 0.05). The cardiac content of TNF-alpha
      and interleukin-1beta (IL-1beta) was not changed by E2 treatment regardless of
      the timing of treatment. Thus, E2 exposure prior to puberty can limit the
      severity of cardiomyopathy in male TNF1.6 mice.

PMID- 15871663
TI  - GB virus type C NS5A sequence polymorphisms: association with interferon
      susceptibility and inhibition of PKR-mediated eIF2alpha phosphorylation.
AB  - GB virus type C (GBV-C) causes persistent infection in humans, although the
      mechanism by which the virus avoids clearance by the host is unknown. To
      determine if amino acid polymorphisms in the GB virus type C (GBV-C) NS5A and E2
      proteins alter response to interferon (IFN) therapy, we studied the sequence of
      GBVC NS5A and E2 obtained from people receiving IFN therapy. In addition, we
      expressed recombinant GBVC NS5A protein to determine if it interferes with RNA
      activated protein kinase (PKR) function in vitro. GBVC NS5A amplified from a
      person whose virus was cleared by IFN therapy (IFN sensitive) demonstrated unique
      amino acid changes occurring in the region that aligns with the hepatitis C virus
      (HCV) IFN sensitivity-determining region (ISDR) compared with NS5A sequences from
      individuals who did not clear GBV-C (IFN resistant). There were no differences in
      the E2 sequences obtained from IFN-sensitive and IFN-resistant isolates. Using a
      yeast genetic system, IFN-resistant NS5A inhibited PKR-mediated phosphorylation
      of eukaryotic initiation factor 2alpha (eIF2alpha) in yeast, whereas IFN
      sensitive NS5A did not inhibit PKR function. GBV-C NS5A amino acid polymorphisms
      appear to be involved in response to IFN therapy, and IFN-resistant GBV-C NS5A
      inhibited PKR-mediated eIF2alpha phosphorylation in a yeast genetic system,
      suggesting a mechanism by which GBV-C may evade clearance by naturally occurring
      host antiviral responses.

PMID- 15871664
TI  - Polymorphisms in the IL-12B gene and outcome of HCV infection.
AB  - Most people with hepatitis C virus (HCV) develop chronic infection with
      persistent viremia. Resolution of infection is associated with antiviral cellular
      immune responses of T helper 1 (Th1) type. Interleukin-12 (IL-12) is a key
      cytokine in the generation of Th1 responses, and functionally relevant
      polymorphisms of the IL12B gene and its promoter have been described recently. We
      sought an association between three IL12B polymorphisms and outcome of HCV
      infection in 195 HCV antibody-positive patients; 123 were chronically infected
      with detectable HCV RNA, and 72 had spontaneously resolved infection testing
      repeatedly negative for HCV RNA. Genotyping was performed for a single nucleotide
      polymorphism (SNP) in the 3'-UTR (1188A/C) of the IL12B gene and for 4-bp
      insertion/deletion polymorphisms in the IL12B promoter region and in the intron 4
      region of the IL12B gene. We found chronically infected patients were
      significantly more likely than those with resolved HCV infection to be homozygous
      for the 3'-UTR A allele (66% vs. 50%; chi-square = 4.12, p = 0.04 with Yates
      correction), which has been associated with lower IL-12 production. No other
      significant association was found. Our findings support the concept that an
      individual's genetically determined ability to produce IL-12 is another factor
      that can influence the outcome of HCV infection.

PMID- 15871665
TI  - Endotoxin contamination contributes to the in vitro cytokine-inducing activity of
      osteopontin preparations.
AB  - Recently, both native and recombinant preparations of human osteopontin (OPN)
      have been shown to be able to induce the production of several proinflammatory
      cytokines in human peripheral blood mononuclear cells (PBMCs) or purified
      monocytes. In the present study, we found that commercially available native and
      recombinant OPNs contain variable amounts of endotoxin (LPS) and that removal of
      endotoxin by polymyxin B-agarose column abrogated their cytokine-inducing
      activity. These results suggest the questionable evidence of the ability of OPN
      to induce several cytokines in human PBMCs and draw attention to the exquisite
      sensitivity of PBMCs/monocytes to endotoxin contaminants.

PMID- 15871666
TI  - Hemolytic anemia during pegylated IFN-alpha2b plus ribavirin treatment for
      chronic hepatitis C: ribavirin is not always the culprit.
AB  - A 53-year-old woman admitted to our department for histologically proven chronic
      hepatitis C had previously been treated with pegylated interferon-alpha2b (PEG
      IFN) plus ribavirin. Combination therapy had been withdrawn after 5 weeks because
      of severe anemia (hemoglobin 8.2 g/dl) despite a reduction in ribavirin dose. A
      second liver biopsy showed moderate chronic hepatitis with portoportal and
      portocentral bridges (Ishak score: grading 14/18, staging 4-5/6). Consequently,
      the patient was retreated with 1.5 microg/kg body weight weekly PEG-IFN and 1000
      mg/day ribavirin. Ribavirin was withdrawn about 3 months later because of anemia.
      After 1 month of PEG-IFN alone, hemoglobin had decreased further to reach 7.9
      g/dl; consequently IFN was stopped. An elevated reticulocyte count, indirect
      bilirubin concentration, and lactic dehydrogenase (LDH) concentration, and a
      positive direct Coombs test (IgG3, C3d also for panagglutinant irregular
      antibodies on eluate) led us to diagnose autoimmune hemolytic anemia (AHA). The
      patient received 1 mg/kg body weight/day prednisone, and all parameters
      normalized within 20 days. This is the first case of IFN-related AHA during PEG
      IFN plus ribavirin therapy. Physicians should be aware that PEG-IFN can be the
      cause of AHA during a ribavirin-containing regimen for chronic hepatitis C.

PMID- 15871669
TI  - Retaining zonal chondrocyte phenotype by means of novel growth environments.
AB  - The loss of phenotype in articular chondrocytes expanded in monolayer has been
      established as a possible contributor to the deficiencies associated with in
      vitro cartilage engineering and autologous cell transplantation procedures. We
      cultured zonal articular chondrocytes on tissue culture plastic, collagen II
      coated polystyrene, and aggrecan-coated polystyrene in an effort to find a
      surface that can either prevent or slow the loss of phenotype. In addition, we
      encapsulated passaged cells in agarose to examine the effect of three-dimensional
      culture on redifferentiating zonal chondrocytes. We used real-time polymerase
      chain reaction to measure the relative gene expression levels of collagen I and
      II, aggrecan, and superficial zone protein over relevant passages (P0-P4).
      Results showed that tissue culture plastic and the collagen II-coated surface
      induced rapid loss of phenotype in zonal articular chondrocytes. The aggrecan
      coated surface had a less detrimental effect on the chondrocytic phenotype of
      seeded cells, inducing gene expression characteristics comparable to those of
      agarose-encapsulated cells. Furthermore, when chondrocytes that had been
      previously passaged on a collagen II surface were placed on an aggrecan surface,
      the zonal cells showed a dramatic change in gene expression from fibroblastic to
      chondrocytic. These results indicate that a culture environment using aggrecan as
      a substratum or agarose as a scaffold is crucial to the development of
      phenotypically correct articular cartilage.

PMID- 15871668
TI  - Control of cellular organization in three dimensions using a microfabricated
      polydimethylsiloxane-collagen composite tissue scaffold.
AB  - Parallel channels of various dimensions have been shown to cause a monolayer of
      cells in culture to align in the direction of the channels. For the engineering
      of complex organ systems to become a reality, similar control over the cellular
      microenvironment in three dimensions must be achieved. Using microfabrication, a
      polydimethylsiloxane (PDMS) scaffold (40 microm wide, 70-microm-deep parallel
      channels separated by 25-microm-wide walls) was created. A fibroblast-seeded
      collagen matrix was then molded around this PDMS scaffold. The PDMS scaffold
      served as an internal skeleton to guide the cells to grow in the prescribed three
      dimensional pattern. Organization, aspect ratio, and the z diameter of the cells
      were analyzed by confocal microscopy. Fibroblasts elongated and organized in the
      direction of the channels throughout the height of the scaffold. The mean angle
      of the cells off of the long axis of the channels was 4.3 +/- 0.7 degrees as
      opposed to 32.6 +/- 2.2 degrees in controls. The morphology of the cells was also
      affected by the PDMS scaffold. The nuclei were longer (1.25x) and thinner (0.75x)
      than in control gels; however, no changes in diameter of the cells in the z
      direction were seen.

PMID- 15871670
TI  - Growth of primary hippocampal neuronal tissue on an aragonite crystalline
      biomatrix.
AB  - Tissue-like structures of hippocampal neurons were established in a crystalline
      three-dimensional (3D) aragonite biomatrix obtained from the exoskeleton of the
      coral Porites lutea. Cultures were maintained in vitro for up to 5 weeks. Cell
      viability and regeneration of neuronal properties were studied by
      immunocytochemical methods, light microscopy image analysis techniques, and
      scanning electron microscopy. Some portions of the cell population acquired the
      morphological characteristics of hippocampal pyramidal or granule neurons with
      axons and dendrites extending in a 3D manner along the surfaces of the
      crystalline biomatrix. The neurons usually grew on a sheet of glial cells. Within
      the pore void areas, multiple layers of neurons were formed, many of the neurons
      growing with no attachment to the crystalline surfaces. The neurons developed
      mature synaptic connections, with presynaptic sites expressing the synaptic
      vesicle protein 2 and postsynaptic sites having the shape of dendritic spines and
      expressing type 1 glutamate receptors, as these cells do under conventional
      culture conditions. The findings of the present study suggest that neuronal
      networks growing in a strong 3D aragonite support may find application as tissue
      replacement material for the central nervous system.

PMID- 15871671
TI  - Adeno-associated virus: a ubiquitous commensal of mammals.

PMID- 15871672
TI  - Custom adeno-associated virus capsids: the next generation of recombinant vectors
      with novel tropism.
AB  - Recombinant gene delivery vehicles based on adeno-associated virus (rAAV) have
      emerged as promising vectors for the correction of genetic and acquired human
      disease states. These vectors possess many characteristics, including low
      pathogenicity and immunogenicity, and long-term gene expression after a single
      administered dose, that make them leading candidates for clinical gene therapy
      applications. Yet, the broad tissue tropism of the available AAV serotypes
      remains a disadvantage for the safest, most effective in vivo delivery of
      transgenes to target tissues. In addition, clinically relevant cell types exist
      that are poorly transduced by current rAAV vectors. As a result, increased
      efforts are now being made to tailor the tropism of rAAV to improve their
      transduction and selectivity profiles. Flexible, diverse methodologies have
      emerged that allow more control over the cell surface receptors rAAV employs for
      cell entry. These novel rAAV production strategies have resulted in unique
      vectors characterized by unique capsid protein sequences that employ alternative
      receptors, and have provided a better understanding of many basic aspects of the
      rAAV life cycle. This review aims to summarize the genetic methods currently
      being employed to customize rAAV capsids.

PMID- 15871673
TI  - Fetal gene transfer using lentiviral vectors and the potential for germ cell
      transduction in rhesus monkeys (Macaca mulatta).
AB  - Genetic modification of germ cells in somatic gene therapy protocols is a
      concern, particularly with fetal approaches. This study focused on the potential
      for germ cell gene transfer post-fetal gene delivery using a human
      immunodeficiency virus type 1 (HIV-1)-derived lentiviral vector pseudotyped with
      the vesicular stomatitis virus-glycoprotein (VSV-G). Rhesus monkey fetuses (n =
      47) were administered vector supernatant (10(7) infectious particles per fetus)
      via the intraperitoneal (IP), intrapulmonary (Ipu), or intracardiac routes (Ica)
      under ultrasound guidance. Tissue harvests were performed near term or 3 months
      postnatal age, and genomic DNA obtained to analyze for vector sequences from
      collected sections of gonads and gonadal cells obtained by laser capture
      microdissection (germ cells, stroma, epithelium). Results indicated no evidence
      of germ cell gene transfer in fetuses or infants with Ipu or Ica routes of
      administration. However, evidence of the transgene (1.33 +/- 0.78 enhanced green
      fluorescent protein [EGFP] copies per copy epsilon-globin) was found in females,
      but not males, when using the IP administration approach (p < 0.05). The highest
      EGFP copies were detected on the surface epithelium (p < 0.05). The results of
      these studies suggest that the HIV-1-derived lentiviral vector pseudotyped with
      VSV-G may transduce a subpopulation of gonadal cells in female fetuses with IP
      administration, whereas no evidence of gene transfer was shown to occur in males
      or with organ-targeting approaches.

PMID- 15871674
TI  - Adeno-associated virus pseudotype 5 vector improves gene transfer in arthritic
      joints.
AB  - The potential for gene delivery to joints, using recombinant adeno-associated
      virus (rAAV) vectors for the treatment of rheumatoid arthritis (RA), has received
      much attention. Different serotypes have different virion shell proteins and, as
      a consequence, vary in their tropism for diverse tissues. The aim of this study
      was to compare the transduction efficiency of different AAV serotypes encoding
      murine secreted alkaline phosphatase (mSEAP) or Escherichia coli beta
      galactosidase for intraarticular gene delivery in an experimental model of
      arthritis. The vectors contained AAV2 terminal repeats flanking the reporter gene
      in an AAV1, AAV2, or AAV5 capsid, producing the pseudotypes rAAV-2/1, rAAV-2/2,
      and rAAV-2/5. Left knee joints of mice with collagen-induced arthritis were
      injected and transgene expression was analyzed by chemiluminescence or direct in
      situ staining of frozen sections. We show for the first time that intraarticular
      gene transfer with AAV- 2/5 was far more efficient than with the other serotypes
      tested. Transgene expression was detectable as early as 7 days after injection,
      reached a maximum at 21 days, and was stably expressed for at least 130 days,
      whereas AAV-2/1- and AAV-2/2-mediated expression levels were barely detectable.
      These findings provide a practical application for future local AAV-mediated gene
      therapy trials in RA.

PMID- 15871675
TI  - Targeting vaccinia to solid tumors with local hyperthermia.
AB  - We have previously demonstrated that mutant vaccinia viruses target tumors in
      vivo after systemic delivery, and they have potential as vectors for tumor
      directed gene therapy. We hypothesized that hyperthermia may augment vaccinia
      delivery to tumors after systemic injection, as hyperthermia increases the
      permeability of the endothelial vasculature to nanoparticles. In our in vitro
      experiments, we have shown that hyperthermia does not alter tumor cells'
      susceptibility to the intrinsic cytopathogenicity of the vaccinia virus compared
      with normothermic controls. Hyperthermia also does not change the viral
      infectivity or the level of viral marker gene expression when compared with
      normothermia. In an in vitro model of endothelial cell monolayer permeability, we
      have demonstrated that hyperthermia increases the permeability of the monolayer
      to vaccinia virus and that this phenomenon is completely reversible. In vivo we
      have demonstrated that the tumors that were treated with systemic vaccinia under
      conditions of hyperthermia (41.5 degrees C for 30 min) had significantly higher
      levels of vaccinia marker gene activity (>100-fold) than those treated under
      normothermic conditions (p < 0.05) and that this effect was specific to tumor. We
      also demonstrated that mice with 1 cm subcutaneous tumors treated with a
      systemically delivered, conditionally replicating vaccinia under conditions of
      hyperthermia had complete tumor regression in 50% and significantly improved
      antitumor response, compared with normothermic viral-treated controls (mean tumor
      volume of 110 mm(3) vs 3169 mm(3), 13 days after treatment) and compared with
      hyperthermic, nonvirally treated control animals (p < 0.0001). Regional
      hyperthermia improves vaccinia targeting to tumors, and thereby enhances the
      antitumor response.

PMID- 15871676
TI  - Lentiviral transduction of primary myeloma cells with CD80 and CD154 generates
      antimyeloma effector T cells.
AB  - The development of immunotherapy approaches designed to obtain tumor-specific T
      cells might help eradicate residual malignant cells in multiple myeloma (MM)
      patients. To this end, we used autologous primary MM cells as antigen-presenting
      cells (APC). Gene transfer of both CD80 and CD154 by lentiviral vectors was
      necessary to significantly improve the APC function of human MM cells.
      Simultaneous CD80/CD154 expression on MM cells allowed the generation of CD8+ T
      cells that recognized unmodified MM cells in 11 of 16 cases, specifically in six
      of six patients with low-stage disease, but only in five of ten patients with
      advanced disease. The activity of CD8+ T cells was MHC restricted and MM
      specific. In seven of seven cases, CD8+ T cell activity was inhibited by
      monoclonal antibodies against HLA class I, and in four of four cases, CD8+ T
      cells recognized autologous MM cells but not autologous normal B and T
      lymphocytes nor bone marrow stromal cells. In addition, the activity of CD8+ T
      cells was directed against allogeneic MM cells that shared at least one MHC
      allele with the autologous counterpart, but not against MHC mismatched MM cells.
      These data lay the ground for the isolation of new MM antigens and for the design
      of vaccination protocols with primary MM cells genetically engineered to express
      immunostimulatory molecules.

PMID- 15871677
TI  - Transfer of a TCR gene derived from a patient with a marked antitumor response
      conveys highly active T-cell effector functions.
AB  - The genes for the alpha and beta chains of a highly reactive anti-MART-1 T-cell
      receptor were isolated from T-lymphocytes that mediated in vivo regression of
      tumor in a patient with metastatic melanoma. These genes were cloned and inserted
      into MSCV-based retroviral vectors. After transduction, greater than 50% gene
      transfer efficiency was demonstrated in primary T-lymphocytes stimulated by an
      anti-CD3 antibody. The specificity and biologic activity of TCR gene-transduced T
      cells was determined by cytokine production after coculture of T-cells with
      stimulator cells pulsed with MART-1 peptide. The production of interferon-gamma
      and granulocyte macrophage-colony stimulating factor (GM-CSF) was comparable to
      highly active MART-1 specific peripheral blood lymphocytes (PBL) in the amount of
      cytokine produced and transduced cells recognized peptide pulsed cells at
      dilutions similar to cytotoxic T lymphocyte (CTL) clones. Human leukocyte antigen
      (HLA) class I restricted recognition was demonstrated by mobilization of
      degranulation marker CD107a, by cell lysis, by cytokine production, and by
      proliferation in the presence of HLA-A2-positive but not HLA-A2-negative melanoma
      cell lines. Similar data was obtained when tumor-infiltrating lymphocytes (TIL)
      were transduced with the TCR genes, converting previously nonreactive cells to
      tumor reactive cells. TCR-transduced T-cells are thus attractive candidates for
      evaluation in cell transfer therapies of patients with cancer.

PMID- 15871678
TI  - Periocular gene transfer of pigment epithelium-derived factor inhibits choroidal
      neovascularization in a human-sized eye.
AB  - Gene transfer provides a potential way to achieve sustained delivery of
      therapeutic proteins to the eye. Studies in rodents have suggested that
      periocular injection of adenoviral vectors containing expression cassettes for
      antiangiogenic proteins results in high intraocular levels of the proteins and
      suppression of choroidal neovascularization (CNV). However, the differences in
      size and scleral thickness between mouse and human eyes make it difficult to
      ascertain if periocular gene transfer is a feasible approach for treating human
      choroidal diseases. To address this issue, we tested the effect of periocular
      injection of an expression cassette for pigment epithelium-derived factor (PEDF)
      packaged in adenoviral vector (AdPEDF.11) in a CNV model in pigs, which have eyes
      that are very similar to humans in size and scleral thickness. Periocular
      injection of beta-galactosidase (AdLacZ.11) resulted in prominent transduction of
      periocular tissues, as was seen in mice. Periocular injection of AdPEDF.11 caused
      increased levels of PEDF in the choroid and significantly reduced the amount of
      CNV at rupture sites in Bruch's membrane. These data suggest that periocular gene
      transfer may be feasible for treatment of human choroidal diseases.

PMID- 15871679
TI  - Gene transfer to respiratory epithelia with lentivirus pseudotyped with
      Jaagsiekte sheep retrovirus envelope glycoprotein.
AB  - A feline immunodeficiency virus (FIV)-based lentiviral vector was pseudotyped to
      identify envelope (env) glycoproteins that direct efficient gene transfer to
      pulmonary epithelia for the treatment or prevention of lung diseases. The
      envelope glycoprotein from the Jaagsiekte sheep retrovirus (JSRV) is a candidate
      under investigation. We utilized high titer FIV vector (>10(8) TU/ml) pseudotyped
      with the JSRV env glycoprotein (JSRVFIV) to study the transduction of polarized
      primary cultures of human airway epithelia and receptor/vector interactions. The
      reported receptor for JSRV, hyaluronidase 2 (HYAL2), is a GPI-linked protein. We
      expressed FLAG-tagged HYAL2 in polarized airway epithelia using an adenoviral
      vector and documented that the HYAL2 protein sorts predominantly to the apical
      surface. Of interest, the efficiency of gene transfer with apically applied JSRV
      FIV was markedly less than FIV pseudotyped with VSV-G, even in Ad-HYAL2
      complemented epithelia. The inefficient gene transfer with JSRV-FIV in HYAL2
      complemented cells suggests that factors other than receptor abundance limit
      apical gene transfer efficiency with this envelope. JSRV-FIV transduced the
      distal lung epithelia of rabbits in vivo and transduced primary cultures of
      rabbit type II cells with 100-fold greater efficiency than primary cultures of
      rabbit tracheal cells. These data indicate that a lentivirus pseudotyped with the
      JSRV envelope glycoprotein transduces type II cells with greater efficiency than
      conducting airway epithelia and provides an example of glycoprotein-mediated cell
      specific tropism within a tissue with a widely heterogeneous cell population.

PMID- 15871680
TI  - Factors associated with induced chronic inflammation in mdx skeletal muscle cause
      posttranslational stabilization and augmentation of extrasynaptic sarcolemmal
      utrophin.
AB  - Chronic inflammation in tibialis anterior muscles of mdx mice was produced by a
      single injection of a recombinant adenovirus vector (AV) expressing an
      immunogenic beta-galactosidase (beta-gal). In regions of intense beta-gal
      staining, mononuclear infiltrates abounded, and muscle fibers showed strong
      extrasynaptic utrophin immunostaining, restoration of dystrophin-associated
      protein complex, and a marked reduction of the prevalence of centronucleation.
      Immunoblot analysis confirmed an increase of endogenous utrophin without an
      increase of the mRNA of the major muscle isoform utrA. Significantly better
      maximal tetanic force values were demonstrated in the inflammatory versus control
      mdx muscles. The resistance to lengthening contraction- induced damage was also
      significantly increased in the former. In muscles of mice lacking TNF-alpha gene,
      AV vector did not induce inflammation and extrajunctional utrophin increase did
      not occur. In the inflammatory mdx muscles, proteolytic activity of calcium
      activated calpain was reduced, and in mdx myotubes in vitro, incubation with NO
      donors also reduced calpain-mediated utrophin proteolysis. Since utrophin was
      shown to be a natural substrate of calpain and known inhibitors of calpain in
      cultured mdx myotubes increased utrophin levels, the above results were
      consistent with the following conclusions: (1) extrasynaptic utrophin increase is
      mainly responsible for the antidystrophic effect; (2) extrasynaptic utrophin
      increase is a result of posttranscriptional mechanism(s) related to
      proinflammatory factors; and (3) reduction of endogenous muscle calpain activity
      by inflammatory cytokines has an important role in the stabilization and increase
      of the extrasynaptic utrophin.

PMID- 15871681
TI  - Elements of style: consent form language and the therapeutic misconception in
      phase 1 gene transfer trials.
AB  - The therapeutic misconception arises wherever human subjects misinterpret the
      primary purpose of a clinical trial as therapeutic. Such misconceptions are
      particularly prevalent in trials involving severely ill subjects or novel and
      well-publicized investigational agents. In order to identify possible sources of
      the therapeutic misconception in gene transfer trials, 286 phase 1 human gene
      transfer consent documents were analyzed for their description of purpose,
      alternatives, and their use of the term gene transfer. We report that 20% of
      trials fail to explain their purpose as safety and dosage, only 41% of oncology
      trials identify comfort care as an alternative to participation, and that the
      term gene therapy is used with twice the frequency of the term gene transfer.
      Trends and coherence in consent form language were analyzed as well. Our results
      indicate that consent forms used in gene transfer phase 1 trials often contain
      language that promotes, or does little to deter, therapeutic misconceptions.

PMID- 15871682
TI  - GDNF delivery using human neural progenitor cells in a rat model of ALS.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by progressive loss of spinal cord, brainstem, and cortical motor
      neurons. In a minority of patients, the disease is caused by mutations in the
      copper (2+)/zinc (2+) superoxide dismutase 1 (SOD1) gene. Recent evidence
      suggests that astrocytes are dysfunctional in ALS and may be a critical link in
      the support of motor neuron health. Furthermore, growth factors, such as glial
      cell line-derived neurotrophic factor (GDNF), have a high affinity for motor
      neurons and can prevent their death following various insults, but due to the
      protein's large size are difficult to directly administer to brain. In this
      study, human neural progenitor cells (hNPC) isolated from the cortex were
      expanded in culture and modified using lentivirus to secrete GDNF (hNPC(GDNF)).
      These cells survived up to 11 weeks following transplantation into the lumbar
      spinal cord of rats overexpressing the G93A SOD1 mutation (SOD1 (G93A)). Cellular
      integration into both gray and white matter was observed without adverse
      behavioral effects. All transplants secreted GDNF within the region of cell
      survival, but not outside this area. Fibers were seen to upregulate cholinergic
      markers in response to GDNF, indicating it was physiologically active. We
      conclude that genetically modified hNPC can survive, integrate, and release GDNF
      in the spinal cord of SOD1 (G93A) rats. As such, they provide an interesting
      source of cells for both glial replacement and trophic factor delivery in future
      human clinical studies.

PMID- 15871683
TI  - Gene targeting by adeno-associated virus vectors is cell-cycle dependent.
AB  - Adeno-associated virus (AAV) vectors can be used to introduce site-specific
      mutations into homologous chromosomal sequences. There are many potential
      applications of this technique, but the process of AAV-mediated gene targeting
      and factors that influence targeting efficiency are not completely understood. We
      investigated the dependence of AAV-mediated gene targeting on the host cell-cycle
      status. The frequency of gene targeting by AAV vectors was compared in dividing
      and serum-arrested normal human fibroblast cultures. Gene targeting occurred in
      arrested fibroblast cultures at 0.15 to 1.1% the frequency of dividing cultures,
      and only took place in cells that had undergone DNA synthesis. Gene targeting was
      also reduced when DNA synthesis was inhibited by hydroxyurea.

PMID- 15871684
TI  - Lentiviral vector-transduced dendritic cells induce specific T cell response in a
      nonhuman primate model.
AB  - Dendritic cells (DCs) are effective in stimulating and controlling the outcome of
      T cell responses. Human immunodeficiency virus type 1-based lentiviral vectors
      can achieve sustained transduction of genes/antigens in dividing and nondividing
      cells, thus representing a candidate vector for stable expression of antigens in
      DCs. We previously established conditions for transduction of purified cytokine
      mobilized rhesus CD34(+) cells in vitro, and transplantation of the autologous
      transduced cells in a nonhuman primate model in vivo. In the present study, we
      transplanted DCs derived from EGFP-transduced CD34(+) cells into nonmyeloablated
      rhesus macaques. Transplantation of DCs stably expressing EGFP into autologous
      animals induces persistent, long-lived (up to 100 weeks) EGFP-specific T cell
      responses. Of note, no humoral responses against EGFP are detected in the
      transplanted animals. These studies provide, to our knowledge, the first
      demonstration that lentiviral transduction of CD34(+) progenitor cells
      subsequently differentiated to DCs is capable of priming a specific T cell
      response in a nonhuman primate in vivo. Taken together, our data provide formal
      in vivo evidence that lentivirus-transduced dendritic cells represent a potential
      approach in eliciting cellular immune responses in primates.

PMID- 15871687
TI  - An interview with Peter J. Coassin. Interview by Vicki Glaser.

PMID- 15871685
TI  - The nonviral episomal replicating vector pEPI-1 allows long-term inhibition of
      bcr-abl expression by shRNA.
AB  - The inhibition of gene expression by RNA interference harbors a high potential
      for application in the therapy of human diseases. However, while exogenous
      application of siRNAs efficiently inhibits gene expression, these effects are
      only transient in mammalian cells. We designed a short hairpin RNA-expression
      cassette to target the bcr-abl oncogene that was then introduced into the
      nonviral vector system pEPI-1, which replicates episomally in the absence of
      selection in the bcr-abl-positive cell line K562. Forty-two days after
      transfection the bcr-abl- but not the cytokine-dependent growth rate was found to
      be drastically reduced in K562 cells. Western analysis revealed a more than 90%
      reduction in the expression of the fusion protein bcr-abl while the expression of
      the bcr protein remained unaffected. In addition, we show that the level of bcr
      abl mRNA was specifically reduced in these cells for more than 90%. These results
      demonstrate that the vector system pEPI-1 allows specific and efficient long term
      gene suppression by using a short hairpin RNA transcription unit.

PMID- 15871688
TI  - High-content screening assay for activators of the Wnt/Fzd pathway in primary
      human cells.
AB  - We have developed a high-content screening (HCS) assay to find activators of
      Wnt/Frizzled (Wnt/Fzd), a pathway known to be important in bone formation.
      Utilizing primary human preosteoblasts as a model, activation of the Wnt/Fzd
      pathway was detected by monitoring the stabilization and translocation of the
      transcription factor beta-catenin from cytoplasm to the nucleus. Endogenous beta
      catenin was detected in preosteoblasts by immunofluorescent staining, and
      subcellular localization was determined by HCS using the Cellomics (Pittsburgh,
      PA) ArrayScan IV. Positive controls, including Wnt3A-conditioned medium and
      inhibitors of glycogen synthase kinase-3beta, resulted in increased nuclear beta
      catenin. The assay had a Z'-factor of 0.6 and was conducive to automation for
      high-throughput screening/HCS. By combining standard immunofluorescence
      technology with automated fluorescence microscopy, we demonstrate the capability
      of screening cell-signaling pathways in primary human cells.

PMID- 15871689
TI  - High-throughput screening using beta-lactamase reporter-gene technology for
      identification of low-molecular-weight antagonists of the human gonadotropin
      releasing hormone receptor.
AB  - G-protein coupled receptors (GPCRs) signal via G-proteins to intracellular second
      messengers. Assays that link transcription of a detectable reporter to promoters
      that are activated by such signaling cascades are highly sensitive and allow
      screening for compounds that either activate or inactivate a GPCR of interest.
      This study describes the development and performance of an antagonistic screen on
      the human gonadotropin releasing hormone receptor (GnRH-R). Compounds (245,000)
      were tested in a high-throughput screen using a Chinese hamster ovary cell line
      stably expressing the human GnRH-R and the Ca2+ sensitive reporter nuclear factor
      activated in T-cells/ activator protein-1-beta-lactamase. In total, 4,160 active
      compounds were identified. Colored and toxic compounds, as well as dust and
      compound aggregates, have been depicted as artifacts. To deselect non-target
      hits, several follow-up assays, including luminescent and fluorescent Ca2+
      mobilization assays and radioligand binding, were developed for the GnRH-R. These
      assays were validated using peptide and low-molecular-weight GnRH-R reference
      compounds before hits from screening were also profiled in these assays. For
      several reference compounds the use of different assay technologies resulted in a
      poor correlation of potency values. In conclusion, beta-lactamase as a primary
      high-throughput screening assay is a powerful complementation to other screening
      technologies. The beta-lactamase technology has several advantages, including
      lack of cell lysis and ratiometric read-out, which augments assay robustness.
      Based on technology comparison, it is not adequate to assume that the same hits
      would be found regardless of which assay technology is used.

PMID- 15871690
TI  - Multi-photon excitation of intrinsic protein fluorescence and its application to
      pharmaceutical drug screening.
AB  - The majority of proteins contain intrinsic fluorophores as natural sensors of
      molecular structures, dynamics, and interactions. The intrinsic protein
      fluorescence signal allows for the label-free and, hence, undisturbed and rapid
      study of protein-ligand interactions. Ultraviolet-based drug screening is
      hampered by the background, photobleaching, light scattering, inner filter
      effects, and interfering assay compounds. Such problems can be overcome by means
      of molecular three-photon excitation (3PE) with infrared femtosecond light pulses
      since longer excitation wavelengths result in less Raleigh scattering, and the
      subfemtoliter (confocal-like) 3PE volume minimizes out-of-focus photobleaching,
      background generation, and inner filter effects. We demonstrate the general
      feasibility of 3PE for protein spectroscopy and illustrate the technique's
      excellent potential for high-throughput screening. By using the intrinsic
      fluorescence intensity of a protein-substrate, we were able to discriminate
      between ligands of different affinities in binding assays.

PMID- 15871691
TI  - A configurable three-dimensional microenvironment in a microfluidic channel for
      primary hepatocyte culture.
AB  - We have developed a technique for the in situ three-dimensional (3D)
      immobilization of primary rat hepatocytes within a localized matrix in a
      microfluidic channel that provides a 3D microenvironment incorporating both a
      configurable 3D matrix and fluid perfusion. This is based on the laminar flow
      complex coacervation of a pair of oppositely charged polyelectrolytes, i.e.,
      methylated collagen and a terpolymer of HEMA-MMA-MAA. 3D collagen matrices were
      formed with minimal gelation times (<8 min), were able to entrap cells under
      aqueous noncytotoxic conditions, and permitted culture media to be perfused in
      the microchannel by virtue of the spatial confinement of the 3D matrix on one
      side of the channel. The architecture and stability of the collagen matrix could
      be configured by the use of different material combinations and changes in the
      polyelectrolyte flow rates and retention time. Primary rat hepatocytes cultured
      for 24 h in the 3D matrix within the microchannel showed comparable or enhanced
      cytochrome P450 7-ethoxyresorufin-O-deethylation activity with static controls.
      The configurable 3D microenvironment in the microfluidic channel may be a
      potential 3D culture model of primary hepatocytes for drug testing applications.

PMID- 15871693
TI  - Piezo- and solenoid valve-based liquid dispensing for miniaturized assays.
AB  - Miniaturization of biological assays requires dispensing liquids in the
      submicroliter range of volumes. Accuracy and reproducibility of dispensing this
      range depend on both the dispenser and the receptacle in which the assay is
      constructed. Miniaturization technologies developed by Aurora Discovery, Inc.
      (San Diego, CA) include high-density multiwell plates for assay samples and
      reagent storage, as well as piezo-based and solenoid valve-based liquid
      dispensers. Some basic principles of small-volume dispensing by jetting are
      described to provide context for dispenser design and function. Performance of
      the latest instruments incorporating these dispensing devices is presented.

PMID- 15871692
TI  - Nanoliter homogenous ultra-high throughput screening microarray for lead
      discoveries and IC50 profiling.
AB  - Microfluidic technologies offer the potential for highly productive and low-cost
      ultra-high throughput screening and high throughput selectivity profiling. Such
      technologies need to provide the flexibility of plate-based assays as well as be
      less expensive to operate. Presented here is a unique microarray system (the
      Reaction Biology [Malvern, PA] DiscoveryDot), which runs over 6,000 homogeneous
      reactions per 1" x 3" microarray using chemical libraries or compound dilutions
      printed in 1-nl volumes. A simple and rapid piezo-activation method delivers from
      30 to 300 pl of biochemical targets and detector chemistries to each reaction.
      The fluorescent signals are detected and analyzed with conventional microarray
      scanners and software. The DiscoveryDot platform is highly customizable, and
      reduces consumption of targets and reaction chemistries by >40-fold and the
      consumption of compounds by >10,000-fold, compared to 384-well plate assay. We
      demonstrate here that the DiscoveryDot platform is compatible with conventional
      large-volume well-based reactions, with a Z' factor of >0.6 for many enzymes,
      such as the caspase family enzymes, matrix metalloproteinase, serine proteases,
      kinases, and histone deacetylases. The platform is well equipped for 50%
      inhibitory concentration (IC50) profiling studies of enzyme inhibitors, with up
      to 10 dilution conditions of each test compound printed in duplicate, and each
      microarray chip can generate over 300 IC50 measurements against a given target.

PMID- 15871694
TI  - Precise nanoliter fluid handling system with integrated high-speed flow sensor.
AB  - A system for accurate low-volume delivery of liquids in the micro- to nanoliter
      range makes use of an integrated miniature flow sensor as part of an intelligent
      feedback control loop driving a micro-solenoid valve. The flow sensor is
      hydraulically connected with the pressurized system liquid in the dispensing
      channel and located downstream from the pressure source, above the solenoid
      valve. The sensor operates in a differential mode and responds in real-time to
      the internal flow-pulse resulting from the brief opening interval of the solenoid
      valve leading to a rapid ejection of a fluid droplet. The integral of the flow
      pulse delivered by the sensor is directly proportional to the volume of the
      ejected droplet from the nozzle. The quantitative information is utilized to
      provide active control of the effectively dispensed or aspirated volume by
      adjusting the solenoid valve accordingly. This process significantly enhances the
      precision of the fluid delivery. The system furthermore compensates automatically
      for any changes in the viscosity of the dispensed liquid. The data delivered by
      the flow sensor can be saved and backtracked in order to confirm and validate the
      aspiration and dispensing process in its entirety. The collected dispense
      information can be used for quality control assessments and automatically be made
      part of an electronic record.

PMID- 15871695
TI  - Nanoliter dispensing for uHTS using pin tools.
AB  - Miniaturization of assays is an important objective in Ultra-HTS. One of the
      major obstacles has been to find fluid handling systems capable of reliably and
      accurately delivering between 2 and 200 nl of test compound to assay plates. New
      methods of forming pins, placing slots in the pins, and hydrophobic coatings
      bonded onto the pins solve many of the problems encountered by early pin tools.
      Unlike other low-volume liquid handlers, these new pin tools provide the ability
      to transfer approximately 2 nl-5 microl of compounds. These pin tools can also
      use low-volume source plates (2-10 microl) and achieve an accuracy of better than
      5%. This, coupled with the ability to transfer small volumes directly from the
      compound library to assay plates without an intervening dilution plate, saves
      reagents, throughput time, and consumables and is, therefore, very cost
      effective. Pin tool compound transfers in the 2-100 nl range provide a simple
      method to dilute away from the toxic effect that dimethyl sulfoxide has on some
      assay target cells. The factors that affect liquid transfers by pin tools are
      discussed in detail as well as the advantages and limitations of pin tools.

PMID- 15871698
TI  - The human checkpoint sensor and alternative DNA clamp Rad9-Rad1-Hus1 modulates
      the activity of DNA ligase I, a component of the long-patch base excision repair
      machinery.
AB  - The human checkpoint sensor and alternative clamp Rad9-Rad1-Hus1 can interact
      with and specifically stimulate DNA ligase I. The very recently described
      interactions of Rad9-Rad1-Hus1 with MutY DNA glycosylase, DNA polymerase beta and
      Flap endonuclease 1 now complete our view that the long-patch base excision
      machinery is an important target of the Rad9-Rad1-Hus1 complex, thus enhancing
      the quality control of DNA.

PMID- 15871699
TI  - Practical use of ultrasound at a dedicated breast center.

PMID- 15871700
TI  - The influence of knowledge of mammography findings on the accuracy of breast
      ultrasound in symptomatic women.
AB  - Breast ultrasound is generally interpreted with knowledge of the mammographic
      examination. This study examined the influence of knowledge of mammography
      findings on the accuracy of ultrasound in women with breast symptoms. Subjects
      were sampled from all women 25-55 years of age consecutively attending a breast
      clinic. This included all 240 women shown to have breast cancer and 240 age
      matched women shown not to have cancer. Ultrasound films were prospectively
      reviewed and reported by two radiologists independent of each other and in a
      blinded manner. A two-phase design was used. In the first phase, the radiologists
      provided an opinion on the ultrasound films. In the second phase, the ultrasound
      films were reread with consideration of the corresponding mammographic
      examination. The accuracy of reading the ultrasound with and without knowledge of
      the findings on mammography was compared using sensitivity and specificity, and
      receiver operating characteristics (ROC) curves. Reporting the ultrasound with
      knowledge of mammography (compared to without mammography) improved sensitivity
      and reduced specificity for both radiologists. For one reader, sensitivity
      increased from 77.5% to 86.7% (p = 0.0002) and specificity decreased from 89.7%
      to 85.4% (p = 0.04). For the other reader, sensitivity increased from 81.3% to
      87.5% (p = 0.0023) and specificity decreased from 87.1% to 85.0% (p = 0.27). ROC
      curves for both radiologists showed that reporting ultrasound with knowledge of
      mammography resulted in small (about 3%), but significant improvement in the area
      under the ROC curve. Our study indicates that knowledge of the findings of
      mammography improves the interpretation of breast ultrasound in symptomatic
      women.

PMID- 15871701
TI  - Delayed nipple-sparing modified subcutaneous mastectomy: rationale and technique.
AB  - The problem of nipple-areola complex (NAC) preservation during mastectomy is a
      very intriguing and stimulating issue. In fact, in order to perform an
      oncologically safe operation, no mammary tissue (enclosed in the main
      galactophoric ducts) should remain; on the other hand, without the blood supply
      coming from the breast gland, NAC viability is greatly impaired because the
      surrounding vascular dermal network is not developed enough to support its
      metabolic requirements. We suggest therefore a two-step surgical procedure. The
      first step, on an outpatient basis with local tumescent anesthesia, is a mini
      invasive cutting and coagulating procedure. It addresses the autonomization of
      the vascular supply to the NAC by detaching the galactophore stalk from the
      nipple and coagulating the deep vascular plexus. The second step, under general
      anesthesia and again with tumescent technique, removes the breast within its
      capsule, with careful checks of any remnant and adequate approach to the axilla.
      A subpectoralis prosthesis completes the procedure. In our view, this technique
      is electively suitable for prophylactic mastectomy, but also for stage I breast
      cancer, 2.5 cm from the NAC and 1.5 cm from the skin and pectoralis fascia, and
      it is very safe, simple, and effective.

PMID- 15871702
TI  - Subareolar breast abscesses: characteristics and results of surgical treatment.
AB  - Our objective was to describe the characteristics of subareolar breast abscesses
      and to analyze the results of surgical treatment in relation to the prevention of
      recurrences. Almost 70% of patients smoked more than 10 cigarettes a day. The
      recurrence rate after excision of the lactiferous ducts was 28% and after
      management without excision of the lactiferous ducts was 79% (p < 0.001). Gram
      positive bacteria were isolated more frequently in primary subareolar breast
      abscesses (not significant). Anaerobic microorganisms were more frequently
      cultured in recurring subareolar breast abscesses (p = 0.02). Definitive
      treatment of subareolar breast abscesses should consist of excision of the
      affected lactiferous ducts.

PMID- 15871704
TI  - Effect of lymphatic tumor burden on sentinel lymph node biopsy in breast cancer.
AB  - Distal obstruction of the lymphatics by tumor and extensive tumor infiltration of
      the draining lymph nodes may prevent migration of the tracer to the sentinel
      lymph node (SLN), adversely affecting SLN identification. Rerouting of lymphatic
      drainage may divert flow to internal mammary nodes and cause an alternative
      nonsentinel node to become "sentinel," increasing the risk of a false-negative
      result. A total of 618 breast cancer patients underwent SLN biopsy using 99mTc
      albumin colloid and patent blue V injected peritumorally. This was followed by
      standard axillary node clearance in all patients at the same operation. The
      overall SLN identification and false-negative rates were 96% (593/618) and 7.6%
      (17/223), respectively. There was no difference in the SLN identification rate
      and the false-negative rate with increasing axillary tumor burden (as determined
      by the total number of positive nodes in the axilla). Further detailed analyses
      are based on the 64 patients from one center (Cardiff) who had at least one
      positive SLN and proceeded to axillary clearance. A total of 83 positive SLNs
      were removed from 64 patients. Tumor burden in the positive SLN was assessed by
      measuring the size of the metastasis and percentage replacement of the SLN by
      tumor, and by documenting extranodal invasion. Increasing tumor burden in the SLN
      (as determined by percentage replacement of SLN by tumor and presence of
      extranodal invasion) was associated with decreased radioisotope uptake (p = 0.005
      and p < 0.0001, respectively). There was no correlation between radioisotope
      uptake and the size of the metastasis in the SLN. There was no correlation
      between blue dye uptake, internal mammary drainage on lymphoscintiscan, and tumor
      burden in the positive SLN. In conclusion, increased axillary lymphatic tumor
      burden is not associated with failure to identify a SLN or false-negative results
      when both blue dye and radioisotope are used for SLN biopsy. In an individual
      SLN, the percentage replacement by tumor, but not the absolute size of the
      metastatic deposit is associated with reduced radioisotope uptake. Extranodal
      invasion in the SLN is a marker of lymphatic obstruction and is significantly
      associated with reduced radioisotope uptake. The lymphatic tumor burden does not
      seem to affect blue dye uptake or internal mammary drainage.

PMID- 15871703
TI  - Concordance of the hormone receptors and correlation of HER-2/neu overexpression
      of the metachronous cancers of contralateral breasts.
AB  - The primary objective of this study was to evaluate the relative prevalence of
      estrogen receptor-negative contralateral breast cancer to the first primary
      cancer and to assess the correlation between the relative overexpression of HER
      2/neu in the first primary cancer and contralateral breast cancer. A total of 144
      women diagnosed with cancers in contralateral breasts were identified from the
      Henry Ford Health System tumor registry. Data were retrieved from electronic
      databases and medical records. Women were dichotomized into users and nonusers of
      tamoxifen. Hormone receptors were scored as positive or negative. HER-2/neu
      overexpression, assessed by immunohistochemistry, was scored as 0, 1(+), 2(+), or
      3(+). Concordance between hormone receptors of the two cancers was low (kappa =
      0.27, p = 0.06). Stratification of women by tamoxifen therapy yielded an almost
      fivefold increase in the proportion of estrogen receptor-negative cancers among
      the users, while the proportion of cancers expressing no estrogen receptor
      remained the same among the nonusers (39.6% versus 40.6%). Matched, archived,
      paraffin-embedded specimens of the first and contralateral breast cancers were
      available for 57 women. The correlation between the relative overexpression of
      HER-2/neu between the first primary and the contralateral breast cancer was 0.4
      (p = 0.002). The higher prevalence of estrogen receptor-negative contralateral
      breast cancer among tamoxifen users concurs with previous reports. The biological
      mechanism for this observation is not understood; however, it has been proposed
      that tamoxifen inhibits the proliferation of estrogen receptor-positive breast
      cancer cells, while estrogen receptor-negative cells may continue to grow because
      of selective pressure. The correlation between HER-2/neu overexpression in the
      matched first primary and contralateral breast cancers was statistically
      significant, suggesting that the diagnosis of HER-2/neu overexpression in
      contralateral breast cancer is associated with HER-2/neu overexpression in the
      first primary cancer.

PMID- 15871705
TI  - Cosmesis with bilateral mammoreduction for conservative breast cancer treatment.
AB  - Over 7 years, 57 women with breast cancer underwent lumpectomy and bilateral
      mammoreduction. Physical complaints about large or lax breast shape were the
      predominate rationale. Two patients were immediately lost to follow-up, 55
      patients remained and were followed every 3 months for an average of 1.6 years.
      This is the largest series traceable by computer and literature search. Chart
      review and patient examination in this retrospective review were utilized as the
      basis for data within the article. Collated notes from patients' doctors were
      assessed, as well as documented patient responses to the procedure. Pictures
      without head/face for identifiers were taken of the patients. Chart data were
      collected by clinicians, but were reviewed blindly by a statistician. The overall
      control and cosmesis rates as well as alleviation of heavy breast problems were
      noted. Only 6% of women had fair to poor cosmetic results; the majority (82%) had
      excellent to good results. Women with very large breasts or markedly relaxed
      breast tissue of concern to the patients proved optimal candidates for lumpectomy
      of cancer and bilateral mammoreduction in the conservative treatment of these
      cancers. There was a significant reduction in the physical complaints of the
      patients as well. For women with very pendulous or extremely large breasts,
      lumpectomy and bilateral mammoreduction may prove to be the optimal course of
      action.

PMID- 15871706
TI  - Postlumpectomy Insertion of the MammoSite brachytherapy device using the scar
      entry technique: initial experience and technical considerations.
AB  - For women undergoing breast-conserving surgery, recent reports suggest that in
      selected cases accelerated partial breast irradiation may yield results equal to
      that of whole breast irradiation. Over 31 months, 19 patients underwent
      accelerated partial breast irradiation using the MammoSite as the sole radiation
      treatment following breast-conserving surgery. Seventeen patients had the
      MammoSite inserted postoperatively using the scar entry technique (SET).
      Treatments were delivered using high dose rate iridium 192 given twice a day for
      5 days. Three complications (two minor, one major) occurred. Late radiation
      morbidity and overall cosmetic results were evaluated. Eighty percent of patients
      had either no change from baseline or slight change in skin pigment. More than
      90% had good or excellent overall cosmetic outcomes. Patients undergoing
      accelerated partial breast irradiation with the MammoSite inserted using SET had
      excellent overall cosmetic results. Advantages of the SET over intraoperative
      placement are presented.

PMID- 15871707
TI  - The value of FDG positron emission tomography in the management of patients with
      breast cancer.
AB  - Increasing experience with positron emission tomography (PET) scanning in breast
      cancer patients is revealing a significant role for this imaging modality. This
      report summarizes the experience of 2-[F18]fluoro-2-deoxy-D-glucose (FDG) PET
      scanning in 165 breast cancer patients from the BC Cancer Agency, British
      Columbia, Canada, and reviews the literature on this topic. Using the database at
      PETSCAN Vancouver, we identified imaged patients with a diagnosis of breast
      cancer. We then conducted a retrospective review of these patients' BC Cancer
      Agency charts to extract demographic and follow-up information. Between November
      2000 and March 2003 we identified 165 patients with histologically confirmed
      breast cancer who had undergone PET scanning, were registered at the BC Cancer
      Agency, and had follow-up information. The median patient age was 52 years. The
      sensitivity of PET in detecting axillary metastases was 28%, and the specificity
      was 86%. At diagnosis, 5% of patients were diagnosed with distant metastases. In
      patients undergoing PET scanning because of suspected recurrence, the sensitivity
      and specificity for detecting recurrence were 89% and 88%, respectively. Distant
      metastases were demonstrated in 30% of patients who were thought only to have
      local-regional recurrence. The results suggest that there are two clinical
      situations in which PET appears to be particularly valuable. The first is in the
      evaluation of patients who are suspected of having a tumor recurrence. The other
      is in identifying patients with multifocal or distant sites of malignancy who
      otherwise appear to have an isolated, potentially curable, local-regional
      recurrence.

PMID- 15871708
TI  - Columnar cell hyperplasia and lobular carcinoma in situ coexisting in the same
      duct.

PMID- 15871709
TI  - Lipomatous hemangiopericytoma of the axilla.

PMID- 15871710
TI  - Chondrolipoma of the breast.

PMID- 15871711
TI  - Primary embryonal rhabdomyosarcoma of the breast in an adult female.

PMID- 15871712
TI  - Neglected chest wall radiation-induced ulcers.

PMID- 15871713
TI  - Atypical dermatofibrosarcoma protuberans in the breast.

PMID- 15871714
TI  - Axillary lymph node involvement in primary epithelioid angiosarcoma of the
      breast.

PMID- 15871715
TI  - Disseminated necrosis of the breast associated with purpura fulminans.

PMID- 15871716
TI  - Relationship between octreotide and breast surgery.

PMID- 15871717
TI  - Influence of initial biopsy technique on the ability to identify sentinel nodes
      in breast cancer patients.

PMID- 15871718
TI  - Metachronous bilateral primary breast cancer associated with dermatomyositis.

PMID- 15871719
TI  - Axillary sentinel node involvement by breast cancer coexisting with B-cell
      follicular lymphoma in nonsentinel nodes.

PMID- 15871720
TI  - Diagnostic challenge of secondary (metastatic) ovarian tumors simulating primary
      endometrioid and mucinous neoplasms.
AB  - Secondary (metastatic) neoplasms to the ovary often cause diagnostic problems,
      especially those tumors that produce large, symptomatic ovarian tumors that
      masquerade clinically and pathologically as primary ovarian tumors of surface
      epithelial type. Most of these tumors arise from organs of the digestive system.
      Except for typical Krukenberg tumors, which usually originate in the stomach and
      generally are easily recognized, the most diagnostically problematic secondary
      ovarian tumors are those that originate in the large intestine, appendix, and
      pancreas. Metastases from these sites typically produce histologic patterns
      resembling primary ovarian endometrioid carcinoma or mucinous epithelial
      neoplasms of borderline and malignant types. This review focuses on the
      diagnostic challenge of distinguishing these secondary ovarian tumors from
      primary ovarian neoplasms. Studies on useful or potentially applicable
      immunohistochemical stains are also detailed.

PMID- 15871721
TI  - Immunohistochemical study on so-called follicular cells and folliculostellate
      cells in the human adenohypophysis.
AB  - Non-hormone-secreting cells in human adenohypophysis have been designated as
      either follicular cells (FC) or folliculostellate cells (FSC). They have
      similarly long cytoplasmic processes, and the difference between FC and FSC
      remains unclear. An immunohistochemical study for S-100 protein, cytokeratin (CK,
      detected by AE1/AE3) and glial fibrillary acidic protein (GFAP) was performed in
      autopsy pituitaries. Double immunohistochemistry for S-100 protein and CK
      revealed that there were numerous coexpressed cells. The most frequent type ('CK
      type cell') was cells weakly positive for S-100 protein in the nucleus and for CK
      immunoreactivity in the cytoplasm. The next numerous type ('S-100 protein cell')
      was cells strongly positive for S-100 protein and weakly positive or negative for
      CK. The CK-type cells were frequently observed in the vicinity of follicular
      structures and in neighborhood of adrenocorticotropic hormone -immunoreactive
      cells, and were most likely the cells termed FC. They were often observed around
      necrotic areas. The S-100 protein cells were individually found in the
      circumference of endocrine cell nest, and seemed to be the so-called stellate
      cells. GFAP-positive cells were rare. It is implied that S-100 protein-positive
      FSC could be divided into at least two main subtypes: FC (CK-type cells) and
      stellate cells (S-100 protein cells).

PMID- 15871722
TI  - Utility of cytokeratin 20 and Ki-67 as markers of urothelial dysplasia.
AB  - Reactive urothelial atypia (RUA) can be difficult to differentiate from
      dysplastic urothelium. The goal was to evaluate the efficacy of cytokeratin 20
      (CK20), Ki-67 and E-cadherin (E-Cad) in this regard. Fifty carcinoma in situ
      (CIS) cases, 50 non-neoplastic urothelia (25 normal, 25 reactive urothelial
      atypia (RUA)) and 17 atypia of unknown significance (AUS) cases were evaluated.
      All cases were stained with monoclonal antibodies against Ki-67, CK20 and E-Cad.
      All (100%) normal urothelia showed normal staining patterns. In the CIS group,
      86%, 82% and 20% of cases showed abnormal expression with CK20, Ki-67 and E-Cad,
      respectively. Both Ki-67 and CK20 were positive in 68% of cases. In the RUA
      group, 96%, 72% and 100% of cases showed normal expression patterns with CK20, Ki
      67 and E-Cad, respectively. Of 28% RUA cases with increased Ki-67, none
      demonstrated abnormal CK20 or E-Cad expression. In the AUS group, 47%
      demonstrated abnormal CK20 and increased Ki-67 expression, suggestive of
      urothelial dysplasia/CIS, 29% were negative with both, suggestive of RUA, and the
      remaining 24% cases could not be resolved. In summary, abnormal CK20 is a useful
      adjunct to morphology for confirming dysplasia. Ki-67 by itself is a less
      reliable marker of dysplasia. E-Cad is not a useful marker in this setting.

PMID- 15871723
TI  - Vascular endothelial growth factor mRNA levels quantified by reverse
      transcription-polymerase chain reaction in microdissected breast carcinoma
      tissues are correlated with histological type and grade of both invasive and
      intraductal components.
AB  - In breast cancer, vascular endothelial growth factor (VEGF) is a prognostic
      factor, but the relationship of VEGF mRNA levels with various parameters or tumor
      progression is unclear. VEGF mRNA levels were measured in 48 cases of invasive
      ductal carcinoma by using laser capture microdissection and quantitative reverse
      transcription-polymerase chain reaction (RT-PCR). The mean VEGF mRNA levels were
      compared among different histological types and grades in 41 and 29 samples of
      invasive and intraductal components, respectively. VEGF mRNA levels were always
      higher in cancerous cells than in non-cancerous cells, but mean VEGF mRNA levels
      were not significantly different between invasive component (3.24 +/- 3.18-fold
      the value of non-cancerous tissue) and intraductal component (4.14 +/- 4.43
      fold). They were higher in papillotubular type than in other types, and higher in
      grade 2 carcinomas than in grade 3 carcinomas of invasive component, and higher
      in comedo type than in other types of intraductal component. Mean VEGF mRNA
      levels were higher in the VEGF-immunopositive group than in the VEGF
      immunonegative group. There was no correlation between VEGF mRNA levels and tumor
      size, nodal status, or hormone receptor status. VEGF expression may play an
      important role in the development of both invasive and intraductal carcinoma
      components, especially those carcinoma components of less aggressive histological
      features.

PMID- 15871724
TI  - Human leukocyte antigen-class II-negative long-term cultured human T-cell
      leukemia virus type-I-infected T-cell lines with progressed cytological
      properties significantly induce superantigen-dependent normal T-cell
      proliferation.
AB  - While most human T-cell leukemia virus type-I (HTLV-I)-infected T cells express
      abundant class II antigens, some aggressive-type adult T-cell leukemia (ATL)
      cells lose their expression. To investigate the significance of the class II
      antigen of HTLV-I infected cells, the progressiveness of HTLV-I-infected long
      term cultured T-cell lines was evaluated, and then their antigen-presenting
      capacity was examined using a superantigen, staphylococcus enterotoxin B (SEB).
      Among the cell lines derived from peripheral blood, HPB-ATL-T (ATL-T), HPB-ATL-2
      (ATL-2) and HPB-ATL-O were more progressed than Tax exclusively expressing HPB
      CTL-I (CTL-I), because the former deleted p16 gene (polymerase chain reaction
      (PCR)) and strongly transcribed survivin (reverse transcriptase-PCR). Notably,
      interferon gamma-independent loss of class II expression of ATL-T and ATL-2 was
      found. In antigen-presenting experiments, however, both cell lines induced SEB
      dependent significant T-cell proliferation estimated by [(3)H] thymidine uptake.
      No class II-re-expressed ATL-2 cells were observed in the SEB-presenting cultures
      by indirect immunofluorescence, and only minimum inhibition of SEB-dependent T
      cell response by anti-human leukocyte antigen (HLA)-DR monoclonal antibody was
      observed. These findings suggest that both ATL-T and ATL-2 very effectively
      present SEB to T cells less dependently on class II molecules. These less
      immunogenic leukemic cells of aggressive ATL may contribute to disease
      aggression.

PMID- 15871726
TI  - Pigmented solid-pseudopapillary neoplasm of the pancreas.
AB  - A hitherto unrecognized variant of solid-pseudopapillary neoplasm of the pancreas
      is reported. The tumor presented in the pancreatic head of a 57-year-old female
      patient. It was a well-circumscribed, encapsulated nodule measuring 27 mm in
      diameter, with variegated yellow to brown and gray cut surface. Histologically,
      the neoplasm was composed of uniform polyhedral cells arranged around delicate
      fibrovascular cores retaining their solid pattern in the periphery, whereas
      central parts of the tumor were characterized by the formation of papillae and
      smaller pseudocysts. Neither mitotic activity nor invasive growth were found.
      Immunohistochemically, tumor cells were positive for vimentin, neuron-specific
      enolase, and CD56, whereas they were negative in reactions with antibodies
      directed against other neuroendocrine markers, cytokeratins, melanocytic markers,
      and pancreatic amylase. In addition to these typical findings, intracellular
      pigmented granules were found in the darker brown zones of the tumor. They were
      positively stained in periodic acid-Schiff reaction after diastase digestion,
      sudan black B, and in Schmorl stain. In contrast, they were not stained with
      Fontana-Masson, Ziehl-Neelsen, and Perls stains. Ultrastructurally, the pigment
      consisted of dense granules with lipid droplets resembling modified lysosomes.
      These results exclude the possibility of a melanogenic nature of the pigment and
      instead determine it as lipofuscin.

PMID- 15871725
TI  - Distinguishing between proliferating nodal lymphoid blasts in chronic myelogenous
      leukemia and non-Hodgkin lymphoma: report of three cases and detection of a
      bcr/abl fusion signal by single-cell analysis.
AB  - Lymph node biopsies were analyzed from three patients with chronic myelogenous
      leukemia (CML) showing nodal blast proliferation. Immunohistochemically, the
      blasts from all three patients had an immature marker profile with a T-blast
      population (cCD3+, CD4-, CD7+, CD8-, CD99+, terminal deoxynucleotidyl transferase
      +) and a hematopoietic progenitor cell marker (CD34). In two patients, the blasts
      also expressed myeloid lineage specificity (naphthol AS-D chloroacetate esterase
      activity and myeloperoxidase positivity). However, it was difficult to
      distinguish between blast proliferation in CML and non-Hodgkin lymphoma from
      these immunohistopathological findings alone. Subsequently, bcr gene
      rearrangement and bcr/abl mRNA expression were detected by Southern blot and
      reverse transcription-polymerase chain reaction analysis of the lymph nodes.
      Fluorescence in situ hybridization (FISH) analysis of lymph node touch smears
      also disclosed bcr/abl gene fusion signals in the blasts of all patients,
      confirming that the blasts were derived from Philadelphia chromosome-positive
      CML. Accurate discrimination between the proliferating nodal blasts of CML and
      non-Hodgkin lymphoma is essential for determining subsequent therapy. FISH
      analysis of bcr/abl in single-cell blast preparations is an efficient tool that
      allows rapid, accurate cytopathological diagnosis of extramedullary blast-phase
      CML and its discrimination from non-Hodgkin lymphoma.

PMID- 15871728
TI  - Berry splenic artery aneurysm rupture in association with segmental arterial
      mediolysis and portal hypertension.
AB  - A rare case of berry splenic artery aneurysm (SAA) rupture associated with
      segmental arterial mediolysis (SAM) and portal hypertension is reported. A 66
      year-old woman, diagnosed as having liver cirrhosis and portal hypertension 6
      years earlier, suddenly developed a lancinating pain in the upper abdomen and
      lost consciousness. She recovered consciousness while being transferred to
      hospital by ambulance. During the investigations, her level of consciousness
      suddenly deteriorated. Ultrasonography showed a massive intraperitoneal
      hemorrhage, and she died 5(1/2) h after admission. On gross examination at
      autopsy it was not possible to find the rupture point of the vessel because the
      pancreas was embedded in a massive hematoma. However, careful dissection of the
      pancreatic tail after fixation revealed a berry aneurysm measuring 0.8 cm in
      diameter in a branch adjacent to the bifurcation in the distal third of the main
      splenic artery. Microscopic examination detected a rupture of the aneurysm. The
      histology of the arterial wall proximal to the aneurysm showed typical SAM. In
      general, berry SAA caused by SAM is rare and unlikely to rupture. The SAA in the
      present case likely occurred and ruptured due to the combination of SAM and
      portal hypertension.

PMID- 15871727
TI  - Neuroendocrine carcinoma of the posterior mediastinum arising from a foregut
      cyst.
AB  - Neuroendocrine carcinoma of the posterior mediastinum is extremely rare.
      Described here is a patient with neuroendocrine carcinoma of the posterior
      mediastinum arising from a foregut cyst. A paravertebral mass detected in the
      posterior mediastinum of a 64-year-old man was spherical, solid and yellowish
      white. Some cystic or cleft-like spaces were present. Microscopically, the lesion
      was composed of proliferating round or polygonal tumor cells in a diffuse, solid
      or trabecular fashion with extensive necrosis and high mitotic activity.
      Components of glandular epithelia and smooth muscle layers were evident in the
      cystic wall. Immunohistochemically, the tumor cells were positive for both
      epithelial and neuroendocrine markers, including pan-cytokeratin, chromogranin A
      and synaptophysin. Neuroendocrine marker-positive cells were also present in the
      glandular epithelium of the cystic walls. It was considered that posterior
      mediastinal neuroendocrine carcinoma arose from a foregut cyst. Malignant change
      within a foregut cyst is very uncommon. This is the first report of a
      neuroendocrine carcinoma of the posterior mediastinum arising from a foregut
      cyst.

PMID- 15871729
TI  - Management of lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia: the central role of the patient risk profile.

PMID- 15871730
TI  - Treatment of lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia in relation to the patient's risk profile for progression.
AB  - Lower urinary tract symptoms suggestive of benign prostatic hyperplasia
      (LUTS/BPH) is a slowly progressing disease, with some patients progressing more
      rapidly than others. In 80% of patients who progress this is caused by the
      worsening of symptoms. The physician can predict the risk of progression from the
      patient's clinical profile; increased symptom severity, a poor maximum urinary
      flow rate (Qmax), and a high postvoid residual urine volume (PVR), are major risk
      factors for overall clinical progression of LUTS/BPH. A large baseline prostate
      volume and a high serum prostate-specific antigen (PSA) level are the predominant
      risk factors for developing acute urinary retention. After predicting risk, the
      most appropriate treatment should be established by balancing the benefits of
      treatment against the possible risks and bother resulting from adverse events.
      From the Medical Therapy Of Prostatic Symptoms study it can be concluded that
      monotherapy with an alpha1-adrenoceptor (AR) antagonist is an appropriate
      treatment for many patients with LUTS/BPH. However, for those at high risk of
      progression (those with a large prostate volume and high PSA level), it appears
      more appropriate to add a 5alpha-reductase inhibitor to the alpha1-AR antagonist
      to obtain maximum relief of symptoms, and ideally to halt the progression of the
      disease. This was confirmed by the RAND Appropriateness Method study, in which 12
      urologists determined the most appropriate treatment for patients with LUTS/BPH
      based on their clinical profile, combination of clinical variables and/or risk
      factors. This study also indicates that patients at very high risk of
      progression, with severe obstruction (poor Qmax and high PVR), are potential
      candidates for immediate surgery.

PMID- 15871731
TI  - Treatment of lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia: sexual function.
AB  - Lower urinary tract symptoms suggestive of benign prostatic hyperplasia
      (LUTS/BPH), and sexual dysfunction, are common, highly bothersome conditions in
      older men, and the prevalence of both disorders increases with age. Sexual
      dysfunction manifests mainly as erectile dysfunction (ED), ejaculatory disorders,
      or decreased libido/hypoactive sexual desire (HSD). Whereas both reduced rigidity
      and reduced ejaculate volume are highly prevalent in ageing men, reduced rigidity
      and pain on ejaculation are considered to be most bothersome. Sexual dysfunction
      is much more prevalent in patients with LUTS/BPH than in men with no LUTS/BPH,
      even after controlling for confounding variables such as age or comorbidities.
      Hence LUTS/BPH is considered an independent risk factor for sexual dysfunction.
      Whether this is because of a common underlying pathology, or whether the
      considerable bother associated with LUTS/BPH leads to reduced sexual functioning,
      remains to be elucidated. Despite a decline in the frequency of sexual
      intercourse, as well as in overall sexual functioning, most ageing men report
      regular sexual activity and consider their sex life as an important dimension of
      their quality of life (QoL). However, most patients with LUTS/BPH experience a
      negative effect of their LUTS on their sex life. Hence, treatment of LUTS/BPH
      should aim to at least maintain or, if possible, improve sexual function. Current
      medical treatment of LUTS/BPH consists of monotherapy with alpha1-adrenoceptor
      (AR) antagonists, 5alpha-reductase inhibitors (RIs) or a combination of these.
      Whereas 5alpha-RIs increase the risk of ED, ejaculatory disorders and HSD, alpha1
      AR antagonists can induce ejaculatory disorders, but do not provoke HSD or ED.
      Combined therapy carries the cumulative risk for sexual dysfunction associated
      with either type of drug. As already indicated, ED is generally perceived as more
      bothersome than ejaculatory disorders. In addition, alpha1-AR antagonists
      slightly improve overall sexual function, possibly by increasing blood flow in
      the penis through alpha1-AR blockade and/or to an increased overall QoL from the
      relief of LUTS. It can be concluded that alpha1-AR antagonists constitute a first
      line therapy for LUTS/BPH because they combine good treatment efficacy with very
      few adverse effects on sexual function.

PMID- 15871732
TI  - Treatment of lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia: the cardiovascular system.

PMID- 15871733
TI  - Lower urinary tract symptoms suggestive of benign prostatic hyperplasia: latest
      update on alpha-adrenoceptor antagonists.
AB  - An update of a systematic review of alpha1-adrenoceptor (AR) antagonists in the
      treatment of lower urinary tract symptoms suggestive of benign prostatic
      hyperplasia (LUTS/BPH) showed that these agents have comparable efficacy. The
      total symptom score is improved by 30-45% and maximum urinary flow rate by 15-30%
      vs baseline. alpha1-AR antagonists that can be started at their therapeutic dose
      have a more rapid onset of action than alpha1-AR antagonists that have to be
      titrated. alpha1-AR antagonists can be differentiated according to their
      tolerability. Alfuzosin (especially the 10 mg once daily dose) and tamsulosin
      (especially the 0.4 mg once daily dose) are better tolerated than doxazosin and
      terazosin. However, alfuzosin might induce more cardiovascular adverse events
      (AEs) in the elderly and/or patients with cardiovascular comorbidity and/or
      comedication. Tamsulosin tends to interfere less with blood pressure regulation
      and induce less vasodilatory AEs than alfuzosin, especially in the elderly, and
      is well tolerated in patients with cardiovascular comorbidity and/or
      comedication. Cardiovascular AEs might lead to potentially serious complications
      such as falls, fractures and institutionalization. Abnormal ejaculation has
      mainly been reported in placebo-controlled trials with tamsulosin but in direct
      comparative trials its rate with tamsulosin 0.4 mg was similar to, or only
      slightly higher than, the rate with alfuzosin. In addition, abnormal ejaculation
      is not reported as bothersome by the patient or associated with serious
      complications. It can be concluded that an alpha1-AR antagonist with a low
      potential to interfere with blood pressure regulation and to induce
      cardiovascular AEs, also in patients with cardiovascular comorbidity and/or
      comedication, can be considered a first-choice treatment option in LUTS/BPH.

PMID- 15871734
TI  - Effects of redox cycling compounds on DT diaphorase activity in the liver of
      rainbow trout (Oncorhynchus mykiss).
AB  - BACKGROUND: DT diaphorase (DTD; NAD(P)H:quinone oxidoreductase; EC 1.6.99.2)
      catalyses the two electron reduction of quinones, thus preventing redox cycling
      and consequently quinone dependent production of reactive oxygen species. In rat
      and mouse, a wide range of chemicals including polyaromatic hydrocarbons, azo
      dyes and quinones induces DTD. Bifunctional compounds, such as beta
      naphthoflavone (beta-NF) and benzo(a)pyrene (B(a)P), induce DTD together with
      CYP1A and phase II enzymes by a mechanism involving the aryl hydrocarbon receptor
      (AHR). Monofunctional induction of DTD is mediated through the antioxidant
      response element and does not lead to the induction of AHR dependent enzymes,
      such as CYP1A. The aim of this study was to investigate the effects of
      prooxidants (both bifunctional and monofunctional) on the activity of hepatic DTD
      in rainbow trout (Oncorhynchus mykiss) in order to evaluate DTD suitability as a
      biomarker. We also investigated the effect of beta-NF on hepatic DTD activity in
      perch (Perca fluviatilis), shorthorn sculpin (Myoxocephalus scorpius), eelpout
      (Zoarces viviparus), brown trout (Salmo trutta) and carp (Cyprinus carpio). In
      addition, the effect of short term exposure to prooxidants on catalase activity
      was investigated. RESULTS: In rainbow trout, hepatic DTD activity is induced by
      the bifunctional AHR agonists beta-NF and B(a)P and the monofunctional inducers
      naphthazarin, menadione and paraquat. Although exposure to both B(a)P and beta-NF
      led to a strong 7-ethoxyresorufin-O-deethylase (EROD) induction, none of the
      monofunctional compounds affected the rainbow trout EROD activity. DTD was not
      induced by beta-NF in any of the other fish species. Much higher DTD activities
      were observed in rainbow trout compared to the other fish species. Catalase
      activity was less responsive to short term exposure to prooxidants compared to
      DTD. CONCLUSION: Since rainbow trout hepatic DTD activity is inducible by both
      monofunctional and bifunctional inducers, it is suggested that rainbow trout DTD
      may be regulated by the same mechanisms, as in mammals. The fact that DTD is
      inducible in rainbow trout suggests that the enzyme may be suitable as a part of
      a biomarker battery when rainbow trout is used in environmental studies. It
      appears as if DTD activity in rainbow trout is higher and inducible compared to
      the other fish species studied.

PMID- 15871735
TI  - Paradise -- not without its plagues: overwhelming Blastomycosis pneumonia after
      visit to lakeside cottages in Northeastern Ontario.
AB  - BACKGROUND: Visiting lakes and cottages is a common leisure activity during
      summer among most Canadians and paradise for some. Various leisure activities are
      involved during these visits, including cleaning and 'airing' the cottage after
      long-winters, activities at the lakes and dock building etc, exposing the
      Canadians to moist soil and decaying woods -- a source of white or tan mould --
      Blastomyces dermatitidis that may cause a flu-like illness to severe pneumonia
      that often remains a diagnostic challenge and results in delay in diagnosis and
      appropriate treatment thereby increasing associated morbidity and mortality. CASE
      PRESENTATIONS: Five cases of overwhelming acute blastomycosis pneumonia are
      presented. Four of the five patients presented within few weeks of their visit to
      the cottages and surrounding lakes and all were initially treated as "community
      acquired pneumonia" that resulted in delay in diagnosis and poor outcome in the
      first patient. The first case, however, taught an important lesson that led to
      high-index of suspicion in the others with early diagnosis and improved outcomes.
      Interestingly, all patients were obese and had a shorter incubation period and
      severe clinical course. The possible mechanism for early and severe disease in
      association with obesity is speculated and literature is reviewed. CONCLUSION:
      High-index of suspicion is important in the early diagnosis and appropriate
      management acute blastomycosis pneumonia to improve associated morbidity and
      mortality.

PMID- 15871736
TI  - Weight reduction is not a major reason for improvement in rheumatoid arthritis
      from lacto-vegetarian, vegan or Mediterranean diets.
AB  - OBJECTIVES: Several investigators have reported that clinical improvements of
      patients with rheumatoid arthritis (RA), from participating in therapeutic diet
      intervention studies, have been accompanied by loss of body weight. This has
      raised the question whether weight reduction per se can improve RA. In order to
      test this hypothesis, three previously conducted diet intervention studies,
      comprising 95 patients with RA, were pooled. Together with Age, Gender, and
      Disease Duration, change during the test period in body weight, characterised
      dichotomously as reduction or no reduction (dichoDeltaBody Weight), as well as
      Diet (dichotomously as ordinary diet or test diet), were the independent
      variables. Dependent variables were the difference (Delta) from baseline to
      conclusion of the study in five different disease outcome measures. DeltaESR and
      DeltaPain Score were both characterised numerically and dichotomously
      (improvement or no improvement). DeltaAcute Phase Response, DeltaPhysical
      Function, and DeltaTender Joint Count were characterised dichotomously only.
      Multiple logistic regression was used to analyse associations between the
      independent and the disease outcome variables. RESULTS: Statistically significant
      correlations were found between Diet and three disease outcome variables i.e.
      DeltaAcute-Phase Response, DeltaPain Score, and DeltaPhysical Function. Delta
      Body Weight was univariately only correlated to DeltaAcute-Phase Response but not
      significant when diet was taken into account. CONCLUSION: Body weight reduction
      did not significantly contribute to the improvement in rheumatoid arthritis when
      eating lacto-vegetarian, vegan or Mediterranean diets.

PMID- 15871737
TI  - Comparison of standard exponential and linear techniques to amplify small cDNA
      samples for microarrays.
AB  - BACKGROUND: The need to perform microarray experiments with small amounts of
      tissue has led to the development of several protocols for amplifying the target
      transcripts. The use of different amplification protocols could affect the
      comparability of microarray experiments. RESULTS: Here we compare expression data
      from Pinus taeda cDNA microarrays using transcripts amplified either
      exponentially by PCR or linearly by T7 transcription. The amplified transcripts
      vary significantly in estimated length, GC content and expression depending on
      amplification technique. Amplification by T7 RNA polymerase gives transcripts
      with a greater range of lengths, greater estimated mean length, and greater
      variation of expression levels, but lower average GC content, than those from PCR
      amplification. For genes with significantly higher expression after T7
      transcription than after PCR, the transcripts were 27% longer and had about 2
      percentage units lower GC content. The correlation of expression intensities
      between technical repeats was high for both methods (R2 = 0.98) whereas the
      correlation of expression intensities using the different methods was
      considerably lower (R2 = 0.52). Correlation of expression intensities between
      amplified and unamplified transcripts were intermediate (R2 = 0.68-0.77).
      CONCLUSION: Amplification with T7 transcription better reflects the variation of
      the unamplified transcriptome than PCR based methods owing to the better
      representation of long transcripts. If transcripts of particular interest are
      known to have high GC content and are of limited length, however, PCR-based
      methods may be preferable.

PMID- 15871738
TI  - The two-year impact of first generation protease inhibitor based antiretroviral
      therapy (PI-ART) on health-related quality of life.
AB  - BACKGROUND: Protease inhibitor based antiretroviral therapy (PI-ART) was
      introduced in 1996 and has greatly reduced the incidence of HIV-related morbidity
      and mortality in the industrialised world. PI-ART would thus be expected to have
      a positive effect on health-related quality of life (HRQL). On the other hand,
      HRQL might be negatively affected by strict adherence requirements as well as by
      short and long-term adverse effects. The aim of this study was to assess the
      influence of two years of first generation PI-ART on HRQL in patients with a
      relatively advanced state of HIV-infection. Furthermore, we wanted to investigate
      the relation between developments in HRQL and viral response, self-reported
      adherence and subjective experience of adverse effects in patients with PI-ART.
      METHODS: HRQL was measured by the Swedish Health-Related Quality of Life
      Questionnaire (SWED-QUAL). Sixty-three items from the SWED-QUAL forms two single
      item and 11 multi-item dimension scales. For this study, two summary SWED-QUAL
      scores (physical HRQL composite score and emotional HRQL composite score) were
      created through a data reduction procedure. At the 2-year follow-up measurement
      (see below), items were added to measure adherence and subjective experience of
      adverse effects. Demographic and medical data were obtained from specific items
      in the questionnaires and from the medical files. Seventy-two patients who were
      among the first to receive PI-ART (indinavir or ritonavir based) responded to the
      questionnaire before the start of PI-ART. Of these, 54 responded to the same
      instrument after two years of treatment (13 had died, four had changed clinic and
      one did not receive the questionnaire). RESULTS: The main findings were that the
      emotional HRQL deteriorated during two years of PI-ART, while the physical HRQL
      remained stable. Multiple linear regression analyses showed that experience of
      adverse effects contributed most to the deterioration of emotional HRQL.
      CONCLUSION: In this sample of patients with relatively advanced state of HIV
      infection, our data suggested that a negative development of physical HRQL had
      been interrupted by the treatment and that the emotional dimension of HRQL
      deteriorated during two years after start of PI-ART. Subjective experience of
      adverse effects made a major contribution to the decrease in emotional HRQL. The
      results underline the importance of including HRQL measures in the evaluation of
      new life prolonging therapies.

PMID- 15871739
TI  - Hypervascular nodule in a fibrotic liver overloaded with iron: identification of
      a premalignant area with preserved liver architecture.
AB  - BACKGROUND: The presence of a hypervascular nodule in a patient with cirrhosis is
      highly suggestive of a hepatocellular carcinoma. CASE PRESENTATION: A 55 year old
      man with idiopathic refractory anaemia was addressed for the cure of a recently
      appeared 3.3 cm hypervascular liver nodule. The nodule was not visible on the
      resected fresh specimen, but a paler zone was seen after formalin fixation. The
      surrounding liver was fibrotic (METAVIR score F3) and overloaded with iron.
      However, the paler zone, thought to be the nodule, had in fact a normal
      architecture, was less fibrotic, and contained some "portal tract-like
      structures" (but with arteries only); moreover, this paler area was devoid of
      iron, contained less glycogen and was characterized by foci of clear hepatocytes.
      CONCLUSION: In spite of the absence of architectural distortion, and a normal
      proliferative index, the possibility of premalignancy or malignancy should be
      considered in this type of hypervascular and hyposiderotic nodule, occurring in
      the context of an iron overloaded liver.

PMID- 15871740
TI  - Pediatric appendicitis rupture rate: a national indicator of disparities in
      healthcare access.
AB  - BACKGROUND: The U.S. National Healthcare Disparities Report is a recent effort to
      measure and monitor racial and ethnic disparities in health and healthcare. The
      Report is a work in progress and includes few indicators specific to children. An
      indicator worthy of consideration is racial/ethnic differences in the rate of bad
      outcomes for pediatric acute appendicitis. Bad outcomes for this condition are
      indicative of poor access to healthcare, which is amenable to social and
      healthcare policy changes. METHODS: We analyzed the KID Inpatient Database, a
      nationally representative sample of pediatric hospitalization, to compare rates
      of appendicitis rupture between white, African American, Hispanic and Asian
      children. We ran weighted logistic regression models to obtain national estimates
      of relative odds of rupture rate for the four groups, adjusted for developmental,
      biological, socioeconomic, health services and hospital factors that might
      influence disease outcome. RESULTS: Rupture was a much more burdensome outcome
      than timely surgery and rupture avoidance. Rupture cases had 97% higher hospital
      charges and 175% longer hospital stays than non-rupture cases on average. These
      burdens disproportionately affected minority children, who had 24% - 38% higher
      odds of appendicitis rupture than white children, adjusting for age and gender.
      These differences were reduced, but remained significant after adjusting for
      other factors. CONCLUSION: The racial/ethnic disparities in pediatric
      appendicitis outcome are large and are preventable with timely diagnosis and
      surgery for all children. Furthermore, estimating this disparity using the KID
      survey is a relatively straightforward process. Therefore pediatric appendicitis
      rupture rate is a good candidate for inclusion in the National Healthcare
      Disparities Report. As with most other health and healthcare disparities, efforts
      to reduce disparities in income, wealth and access to care will most likely
      improve the odds of favorable outcome for this condition as well.

PMID- 15871741
TI  - The tissue microarray data exchange specification: a document type definition to
      validate and enhance XML data.
AB  - BACKGROUND: The Association for Pathology Informatics (API) Extensible Mark-up
      Language (XML) TMA Data Exchange Specification (TMA DES) proposed in April 2003
      provides a community-based, open source tool for sharing tissue microarray (TMA)
      data in a common format. Each tissue core within an array has separate data
      including digital images; therefore an organized, common approach to produce,
      navigate and publish such data facilitates viewing, sharing and merging TMA data
      from different laboratories. The AIDS and Cancer Specimen Resource (ACSR) is a
      HIV/AIDS tissue bank consortium sponsored by the National Cancer Institute (NCI)
      Division of Cancer Treatment and Diagnosis (DCTD). The ACSR offers HIV-related
      malignancies and uninfected control tissues in microarrays (TMA) accompanied by
      de-identified clinical data to approved researchers. Exporting our TMA data into
      the proposed API specified format offers an opportunity to evaluate the API
      specification in an applied setting and to explore its usefulness. RESULTS: A
      document type definition (DTD) that governs the allowed common data elements
      (CDE) in TMA DES export XML files was written, tested and evolved and is in
      routine use by the ACSR. This DTD defines TMA DES CDEs which are implemented in
      an external file that can be supplemented by internal DTD extensions for locally
      defined TMA data elements (LDE). CONCLUSION: ACSR implementation of the TMA DES
      demonstrated the utility of the specification and allowed application of a DTD to
      validate the language of the API specified XML elements and to identify possible
      enhancements within our TMA data management application. Improvements to the
      specification have additionally been suggested by our experience in importing
      other institution's exported TMA data. Enhancements to TMA DES to remove
      ambiguous situations and clarify the data should be considered. Better specified
      identifiers and hierarchical relationships will make automatic use of the data
      possible. Our tool can be used to reorder data and add identifiers; upgrading
      data for changes in the specification can be automatically accomplished. Using a
      DTD (optionally reflecting our proposed enhancements) can provide stronger
      validation of exported TMA data.

PMID- 15871742
TI  - The factor validity of the Western Ontario Rotator Cuff Index.
AB  - BACKGROUND: The Western Ontario Rotator Cuff Index (WORC) is a self-report
      questionnaire developed specifically to evaluate disability in persons with
      pathology of the rotator cuff of the shoulder. The authors created items in 5
      categories based on a model of quality of life, but never validated this
      structure. The purpose of this study was to examine the validity of the original
      5-domain model of the WORC by performing factor analysis. METHODS: Three hundred
      twenty nine subjects (age, mean: 52, SD: 12) were tested prior to undergoing
      surgery for rotator cuff pathologies. They completed the WORC, a self-report
      questionnaire, which has 21 items on the effect of the rotator cuff problem on
      symptoms, activities and emotions. Statistical calculations included correlations
      between items, Cronbach's alpha of the total scale and subscales, and principal
      component factor analysis with oblique rotation. RESULTS: Correlations ranged
      from .09 to .70 between all the items, from .29 to .70 between items within a
      subscale, and from .53 to .72 between subscale scores. Cronbach's alpha was .93
      for the total scale, and .72 to .82 for the subscales. The factor analysis
      produced 3 factors that explained 57% of the variance. The first factor included
      symptoms and emotional items, the second included strength items and the third
      included daily activities. CONCLUSION: The results of this study did not support
      the 5-domain model of the WORC.

PMID- 15871743
TI  - Maternal mortality in the rural Gambia, a qualitative study on access to
      emergency obstetric care.
AB  - BACKGROUND: Maternal mortality is the vital indicator with the greatest disparity
      between developed and developing countries. The challenging nature of measuring
      maternal mortality has made it necessary to perform an action-oriented means of
      gathering information on where, how and why deaths are occurring; what kinds of
      action are needed and have been taken. A maternal death review is an in-depth
      investigation of the causes and circumstances surrounding maternal deaths. The
      objectives of the present study were to describe the socio-cultural and health
      service factors associated with maternal deaths in rural Gambia. METHODS: We
      reviewed the cases of 42 maternal deaths of women who actually tried to reach or
      have reached health care services. A verbal autopsy technique was applied for 32
      of the cases. Key people who had witnessed any stage during the process leading
      to death were interviewed. Health care staff who participated in the provision of
      care to the deceased was also interviewed. All interviews were tape recorded and
      analyzed by using a grounded theory approach. The standard WHO definition of
      maternal deaths was used. RESULTS: The length of time in delay within each phase
      of the model was estimated from the moment the woman, her family or health care
      providers realized that there was a complication until the decision to seeking or
      implementing care was made. The following items evolved as important:
      underestimation of the severity of the complication, bad experience with the
      health care system, delay in reaching an appropriate medical facility, lack of
      transportation, prolonged transportation, seeking care at more than one medical
      facility and delay in receiving prompt and appropriate care after reaching the
      hospital. CONCLUSION: Women do seek access to care for obstetric emergencies, but
      because of a variety of problems encountered, appropriate care is often delayed.
      Disorganized health care with lack of prompt response to emergencies is a major
      factor contributing to a continued high mortality rate.

PMID- 15871744
TI  - User fees in private non-for-profit hospitals in Uganda: a survey and
      intervention for equity.
AB  - BACKGROUND: In developing countries, user fees may represent an important source
      of revenues for private-non-for-profit hospitals, but they may also affect
      access, use and equity. METHODS: This survey was conducted in ten hospitals of
      the Uganda Catholic Medical Bureau to assess differences in user fees policies
      and to propose changes that would better fit with the social concern explicitly
      pursued by the Bureau. Through a review of relevant hospital documents and
      reports, and through interviews with key informants, health workers and users,
      hospital and non-hospital cost was calculated, as well as overall expenditure and
      revenues. Lower fees were applied in some pilot hospitals after the survey.
      RESULTS: The percentage of revenues from user fees varied between 6% and 89%
      (average 40%). Some hospitals were more successful than others in getting
      external aid and government subsidies. These hospitals were applying lower fees
      and flat rates, and were offering free essential services to encourage access, as
      opposed to the fee-for-service policies implemented in less successful hospitals.
      The wide variation in user fees among hospitals was not justified by differences
      in case mix. None of the hospitals had a policy for exemption of the poor; the
      few users that actually got exempted were not really poor. To pay hospital and
      non-hospital expenses, about one third of users had to borrow money or sell goods
      and property. The fee system applied after the survey, based on flat and lower
      rates, brought about an increase in access and use of hospital services.
      CONCLUSION: Our results confirm that user fees represent an unfair mechanism of
      financing for health services because they exclude the poor and the sick. To
      mitigate this effect, flat rates and lower fees for the most vulnerable users
      were introduced to replace the fee-for-service system in some hospitals after the
      survey. The results are encouraging: hospital use, especially for pregnancy,
      childbirth and childhood illness, increased immediately, with no detrimental
      effect on overall revenues. A more equitable user fees system is possible.

PMID- 15871745
TI  - In vitro identification and in silico utilization of interspecies sequence
      similarities using GeneChip technology.
AB  - BACKGROUND: Genomic approaches in large animal models (canine, ovine etc) are
      challenging due to insufficient genomic information for these species and the
      lack of availability of corresponding microarray platforms. To address this
      problem, we speculated that conserved interspecies genetic sequences can be
      experimentally detected by cross-species hybridization. The Affymetrix platform
      probe redundancy offers flexibility in selecting individual probes with high
      sequence similarities between related species for gene expression analysis.
      RESULTS: Gene expression profiles of 40 canine samples were generated using the
      human HG-U133A GeneChip (U133A). Due to interspecies genetic differences, only 14
      +/- 2% of canine transcripts were detected by U133A probe sets whereas profiling
      of 40 human samples detected 49 +/- 6% of human transcripts. However, when these
      probe sets were deconstructed into individual probes and examined performance of
      each probe, we found that 47% of human probes were able to find their targets in
      canine tissues and generate a detectable hybridization signal. Therefore, we
      restricted gene expression analysis to these probes and observed the 60% increase
      in the number of identified canine transcripts. These results were validated by
      comparison of transcripts identified by our restricted analysis of cross-species
      hybridization with transcripts identified by hybridization of total lung canine
      mRNA to new Affymetrix Canine GeneChip. CONCLUSION: The experimental
      identification and restriction of gene expression analysis to probes with
      detectable hybridization signal drastically increases transcript detection of
      canine-human hybridization suggesting the possibility of broad utilization of
      cross-hybridizations of related species using GeneChip technology.

PMID- 15871746
TI  - Coping, quality of life, and hope in adults with primary antibody deficiencies.
AB  - BACKGROUND: Living with a chronic disease, such as primary antibody deficiency,
      will often have consequences for quality of life. Previous quality-of-life
      studies in primary antibody deficiency patients have been limited to different
      treatment methods. We wanted to study how adults with primary antibody
      deficiencies manage their conditions and to identify factors that are conducive
      to coping, good quality of life and hope. METHODS: Questionnaires were sent to
      all patients > or =20 years of age with primary antibody deficiencies who were
      served by Rikshospitalet University Hospital. The questionnaires consisted of
      several standardized scales: Ferrans and Powers Quality of Life Index (QLI),
      Short Form-36 (SF-36), Jalowiec Coping Scale (JCS), Nowotny Hope Scale (NHS), and
      one scale we devised with questions about resources and pressures in the past. Of
      a total of 91, 55 patients (aged 23-76 years) answered the questionnaires. The
      questionnaire study were supplemented with selected interviews of ten extreme
      cases, five with low and five with high quality of life scores. RESULTS: Among
      the 55 patients, low quality of life scores were related to unemployment,
      infections in more than four organs, more than two additional diseases, or more
      than two specific occurrences of stress in the last 2-3 months. Persons with
      selective IgA deficiency had significantly higher QLI scores than those with
      other antibody deficiencies. An optimistic coping style was most frequent used,
      and hope values were moderately high. Based on the interviews, the patients could
      be divided into three groups: 1) low QLI scores, low hope values, and reduced
      coping, 2) low QLI scores, moderate hope values, and good coping, and 3) high QLI
      scores, moderate to strong hope values, and good coping. Coping was related to
      the patients' sense of closeness and competence. CONCLUSION: Low quality of life
      scores in adults with primary antibody deficiencies were linked to unemployment
      and disease-related strains. Closeness and competence were preconditions for
      coping, quality of life and hope. The results are valuable in planning care for
      this patient group.

PMID- 15871747
TI  - Oogenesis in cultures derived from adult human ovaries.
AB  - Ten years ago, we reported that in adult human females the ovarian surface
      epithelium (OSE) is a source of germ cells. Recently, we also demonstrated that
      new primary follicles are formed by assembly of oocytes with nests of primitive
      granulosa cells in the ovarian cortex. The components of the new primary
      follicles, primitive granulosa and germ cells, differentiated sequentially from
      the OSE, which arises from cytokeratin positive mesenchymal progenitor cells
      residing in the ovarian tunica albuginea. In the present study, we investigated
      the possibility that the oocytes and granulosa cells may differentiate in
      cultures derived from adult human ovaries. Cells were scrapped from the surface
      of ovaries and cultured for 5 to 6 days, in the presence or absence of estrogenic
      stimuli [phenol red (PhR)]. The OSE cells cultured in the medium without PhR
      differentiated into small (15 micron) cells of granulosa phenotype, and
      epithelial, neural, and mesenchymal type cells. In contrast, OSE cells cultured
      in the presence of PhR differentiated directly into large (180 micron) cells of
      the oocyte phenotype. Such cells exhibited germinal vesicle breakdown, expulsion
      of the polar body, and surface expression of zona pellucida proteins, i.e.
      characteristics of secondary oocytes. These in vitro studies confirm our in vivo
      observations that in adult human ovaries, the OSE is a bipotent source of oocytes
      and granulosa cells. Development of numerous mature oocytes from adult ovarian
      stem cells in vitro offers new strategies for the egg preservation, IVF
      utilization, and treatment of female infertility. In addition, other clinical
      applications aiming to utilize stem cells, and basic stem cell research as well,
      may employ totipotent embryonic stem cells developing from fertilized oocytes.

PMID- 15871748
TI  - Investigation of Staphylococcus strains with heterogeneous resistance to
      glycopeptides in a Turkish university hospital.
AB  - BACKGROUND: The hetero-glycopeptide intermediate staphylococci is considered to
      be the precursor of glycopeptide intermediate staphylococci especially vancomycin
      intermediate Staphylococcus aureus (VISA). For this purpose, we aimed to
      investigate the heterogeneous resistance to glycopeptide and their frequencies in
      135 Staphylococcus strains. METHODS: Heterogeneous resistance of Staphylococcus
      strains was detected by inoculating the strains onto Brain Heart Infusion agar
      supplemented with 4 mg/L of vancomycin (BHA-V4). Agar dilution method was used
      for determining MICs of glycopeptides and population analysis profile was
      performed for detecting frequency of heterogeneous resistance for the parents of
      selected strains on BHA-4. RESULTS: Eight (6%) out of 135 Staphylococcus strains
      were exhibited heterogeneous resistance to at least one glycopeptide. One (1.2%)
      out of 81 S. aureus was found intermediate resistance to teicoplanin (MIC 16
      mg/L). Other seven strains were Staphylococcus haemolyticus (13%) out of 54
      coagulase negative staphylococci (CoNS). Six of the seven strains were detected
      heterogeneously reducing susceptibility to vancomycin (MICs ranged between 5-8
      mg/L) and teicoplanin (MICs ranged between 32-64 mg/L), and one S. haemolyticus
      was found heterogeneous resistance to teicoplanin (MIC 32 mg/L). Frequencies of
      heterogeneous resistance were measured being one in 10(6) - 10(7) cfu/ml. MICs of
      vancomycin and teicoplanin for hetero-staphylococci were determined as 2-6 folds
      and 3-16 folds higher than their parents, respectively. These strains were
      isolated from six patients (7%) and two (4%) of health care workers hands. Hetero
      VISA strain was not detected. CONCLUSION: Heterogeneous resistance to
      glycopeptide in CoNS strains was observed to be significantly more emergent than
      those of S. aureus strains (vancomycin P 0.001, teicoplanin, P 0.007). The
      increase MICs of glycopeptide resistance for subpopulations of staphylococci
      comparing with their parents could be an important clue for recognizing the early
      steps in the appearance of VISA strains. We suggested to screen clinical S.
      aureus and CoNS strains, systematically, for the presence of heterogeneously
      resistance to glycopeptide.

PMID- 15871749
TI  - Assessing the dose of supplemental oxygen: let us compare methodologies.

PMID- 15871750
TI  - Noninvasive positive-pressure ventilation in patients with chronic obstructive
      pulmonary disease exacerbation: not too late but not too soon?

PMID- 15871751
TI  - Inhalers in asthma management: is demonstration the key to compliance?

PMID- 15871752
TI  - Is there too much "pulmonary" in cardiopulmonary resuscitation?

PMID- 15871753
TI  - Delivered oxygen concentrations using low-flow and high-flow nasal cannulas.
AB  - INTRODUCTION: Nasal cannulas are commonly used to deliver oxygen in acute and
      chronic care settings; however, there are few data available on delivered
      fraction of inspired oxygen (F(IO(2))). The purposes of this study were to
      determine the delivered F(IO(2)) on human subjects using low-flow and high-flow
      nasal cannulas, and to determine the effects of mouth-closed and mouth-open
      breathing on F(IO(2)). METHODS: We measured the pharyngeal F(IO(2)) delivered by
      adult nasal cannulas at 1-6 L/min and high-flow nasal cannulas at 6-15 L/min
      consecutively in 10 normal subjects. Oxygen was initiated at 1 L/min, with the
      subject at rest, followed by a period of rapid breathing. Gas samples were
      aspirated from a nasal catheter positioned with the tip behind the uvula. This
      process was repeated at each liter flow. Mean, standard deviation, and range were
      calculated at each liter flow. F(IO(2)) during mouth-open and mouth-closed
      breathing were compared using the dependent test for paired values, to determine
      if there were significant differences. RESULTS: The mean resting F(IO(2)) ranged
      from 0.26-0.54 at 1-6 L/min to 0.54-0.75 at 6-15 L/min. During rapid breathing
      the mean F(IO(2)) ranged from 0.24-0.45 at 1-6 L/min to 0.49-0.72 at 6-15 L/min.
      The mean F(IO(2)) increased with increasing flow rates. The standard deviation
      (+/- 0.04-0.15) and range were large, and F(IO(2)) varied widely within and
      between subjects. F(IO(2)) during mouth-open breathing was significantly (p <
      0.05) greater than that during mouth-closed breathing. CONCLUSIONS: F(IO(2))
      increased with increasing flow. Subjects who breathed with their mouths open
      attained a significantly higher F(IO(2)), compared to those who breathed with
      their mouths closed.

PMID- 15871754
TI  - Noninvasive positive-pressure ventilation in patients with milder chronic
      obstructive pulmonary disease exacerbations: a randomized controlled trial.
AB  - OBJECTIVES: To determine the effect of the addition of noninvasive positive
      pressure ventilation (NPPV) to standard medical therapy on length of hospital
      stay among patients presenting with mild exacerbations of chronic obstructive
      pulmonary disease (COPD) requiring hospitalization. DESIGN: Randomized controlled
      unblinded study with concealed allocation. SETTING: Respiratory ward of a single
      center, academic, tertiary-care hospital. PARTICIPANTS: Patients with a prior
      history of COPD who presented with a recent onset of shortness of breath and a pH
      of > 7.30 were eligible for inclusion in the study. INTERVENTIONS: NPPV daily for
      3 days for intervals of 8, 6, and 4 hours, respectively, plus standard therapy,
      versus standard therapy alone. MEASUREMENTS: Borg dyspnea index at baseline, 1
      hour, and daily. Length of hospital stay, endotracheal intubation, hospital
      survival. RESULTS: We found that NPPV was generally poorly tolerated, with only
      12 of 25 patients wearing it for the prescribed 3 days. With the exception of a
      decrease in dyspnea at 1 hour and 2 days, significant between-group differences
      were not seen for any measured variable. CONCLUSIONS: The effectiveness and cost
      effectiveness of the addition of NPPV to standard therapy in milder COPD
      exacerbations remains unclear. P(aCO(2)) related to this increased WOB that
      requires intervention with some form of assisted ventilation. All patients
      developing an exacerbation of COPD that requires hospitalization have an
      increased WOB and, we hypothesize, potentially develop some degree of associated
      respiratory muscle fatigue. We further hypothesize that adding intermittent NPPV
      during the initial days of hospital stay would afford respiratory muscle rest for
      patients with milder COPD exacerbations and that this rest would allow these
      patients to recover more quickly and to be discharged home earlier. The objective
      of this trial was to determine whether the addition of NPPV to standard therapy
      during the first 3 days of admission in milder COPD exacerbations could decrease
      length of hospital stay.

PMID- 15871755
TI  - Counseling about turbuhaler technique: needs assessment and effective strategies
      for community pharmacists.
AB  - Optimal effects of asthma medications are dependent on correct inhaler technique.
      In a telephone survey, 77/87 patients reported that their Turbuhaler technique
      had not been checked by a health care professional. In a subsequent pilot study,
      26 patients were randomized to receive one of 3 Turbuhaler counseling techniques,
      administered in the community pharmacy. Turbuhaler technique was scored before
      and 2 weeks after counseling (optimal technique = score 9/9). At baseline, 0/26
      patients had optimal technique. After 2 weeks, optimal technique was achieved by
      0/7 patients receiving standard verbal counseling (A), 2/8 receiving verbal
      counseling augmented with emphasis on Turbuhaler position during priming (B), and
      7/9 receiving augmented verbal counseling plus physical demonstration (C)
      (Fisher's exact test for A vs C, p = 0.006). Satisfactory technique (4 essential
      steps correct) also improved (A: 3/8 to 4/7; B: 2/9 to 5/8; and C: 1/9 to 9/9
      patients) (A vs C, p = 0.1). Counseling in Turbuhaler use represents an important
      opportunity for community pharmacists to improve asthma management, but physical
      demonstration appears to be an important component to effective Turbuhaler
      training for educating patients toward optimal Turbuhaler technique.

PMID- 15871756
TI  - Positive expiratory pressure device acceptance by hospitalized children with
      sickle cell disease is comparable to incentive spirometry.
AB  - BACKGROUND: The pulmonary complication in sickle cell disease known as acute
      chest syndrome (ACS) has potential for high morbidity and mortality. A randomized
      trial demonstrated that incentive spirometry (IS) reduces the rate of ACS,
      leading to a role for respiratory therapy in hospital management of sickle cell
      pain. However, use of IS can be limited by chest wall pain, or by difficulty with
      the coordinated inspiration in a young child. Intermittent positive expiratory
      pressure (PEP) therapy may be easier for a child's coordination and more
      comfortable than IS for a child with chest wall pain. PURPOSE: To compare PEP
      therapy with conventional IS for children hospitalized for sickle cell pain with
      respect to patient satisfaction, length of hospital stay, and progression to ACS.
      METHODS: This pilot study enrolled 20 children upon hospitalization for sickle
      cell pain in the thorax, randomly assigning them to either PEP (n = 11) or IS (n
      = 9) therapy, administered by a therapist hourly while awake. RESULTS: The
      randomization assigned an older distribution to PEP than IS (12.3 vs 8.8 y).
      Patient satisfaction was high for both respiratory care devices, and there was no
      difference between the PEP and IS groups (4.5 vs 4.4, p = 0.81). Length of
      hospital stay was similar (5 vs 4.3 d, p = 0.56). No children in either group
      progressed to ACS. CONCLUSION: These preliminary results show no difference in
      the primary outcomes in the 2 groups. Intermittent PEP therapy warrants further
      study as an alternative to IS for sickle cell patients at high risk for ACS, as
      effective preventive respiratory therapy.

PMID- 15871757
TI  - Reducing ventilation frequency during cardiopulmonary resuscitation in a porcine
      model of cardiac arrest.
AB  - INTRODUCTION: American Heart Association/American College of Cardiology
      guidelines recommend a compression-to-ventilation ratio (C/V ratio) of 15:2
      during cardiopulmonary resuscitation (CPR) for out-of-the-hospital cardiac
      arrest. Recent data have shown that frequent ventilations are unnecessary and may
      be harmful during CPR, since each positive-pressure ventilation increases
      intrathoracic pressure and may increase intracranial pressure and decrease venous
      blood return to the right heart and thereby decrease both the cerebral and
      coronary perfusion pressures. HYPOTHESIS: We hypothesized that reducing the
      ventilation rate by increasing the C/V ratio from 15:2 to 15:1 will increase
      vital-organ perfusion pressures without compromising oxygenation and acid-base
      balance. METHODS: Direct-current ventricular fibrillation was induced in 8 pigs.
      After 4 min of untreated ventricular fibrillation without ventilation, all
      animals received 4 min of standard CPR with a C/V ratio of 15:2. Animals were
      then randomized to either (A) a C/V ratio of 15:1 and then 15:2, or (B) a C/V
      ratio of 15:2 and then 15:1, for 3 min each. During CPR, ventilations were
      delivered with an automatic transport ventilator, with 100% oxygen. Right atrial
      pressure, intratracheal pressure (a surrogate for intrathoracic pressure), aortic
      pressure, and intracranial pressure were measured. Coronary perfusion pressure
      was calculated as diastolic aortic pressure minus right atrial pressure. Cerebral
      perfusion pressure was calculated as mean aortic pressure minus mean intracranial
      pressure. Arterial blood gas values were obtained at the end of each
      intervention. A paired t test was used for statistical analysis, and a p value <
      0.05 was considered significant. RESULTS: The mean +/- SEM values over 1 min with
      either 15:2 or 15:1 C/V ratios were as follows: intratracheal pressure 0.93 +/-
      0.3 mm Hg versus 0.3 +/- 0.28 mm Hg, p = 0.006; coronary perfusion pressure 10.1
      +/- 4.5 mm Hg versus 19.3 +/- 3.2 mm Hg, p = 0.007; intracranial pressure 25.4 +/
      2.7 mm Hg versus 25.7 +/- 2.7 mm Hg, p = NS; mean arterial pressure 33.1 +/- 3.7
      mm Hg versus 40.2 +/- 3.6 mm Hg, p = 0.007; cerebral perfusion pressure 7.7 +/-
      6.2 mm Hg versus 14.5 +/- 5.5 mm Hg, p = 0.008. Minute area intratracheal
      pressure was 55 +/- 17 mm Hg . s versus 22.3 +/- 10 mm Hg . s, p < 0.001. End
      tidal CO(2) with 15:2 versus 15:1 was 24 +/- 3.6 mm Hg versus 29 +/- 2.5 mm Hg,
      respectively, p = 0.001. Arterial blood gas values were not significantly changed
      with 15:2 versus 15:1 C/V ratios: pH 7.28 +/- 0.03 versus 7.3 +/- 0.03; P(aCO(2))
      37.7 +/- 2.9 mm Hg versus 37.6 +/- 3.5 mm Hg; and P(aO(2)) 274 +/- 36 mm Hg
      versus 303 +/- 51 mm Hg. CONCLUSIONS: In a porcine model of ventricular
      fibrillation cardiac arrest, reducing the ventilation frequency during CPR by
      increasing the C/V ratio from 15:2 to 15:1 resulted in improved vital-organ
      perfusion pressures, higher end-tidal CO(2) levels, and no change in arterial
      oxygen content or acid-base balance.

PMID- 15871758
TI  - Evaluation of resistance in 8 different heat-and-moisture exchangers: effects of
      saturation and flow rate/profile.
AB  - INTRODUCTION: When endotracheal intubation is required during ventilatory
      support, the physiologic mechanisms of heating and humidifying the inspired air
      related to the upper airways are bypassed. The task of conditioning the air can
      be partially accomplished by heat-and-moisture exchangers (HMEs). OBJECTIVES: To
      evaluate and compare with respect to imposed resistance, different types/models
      of HME: (1) dry versus saturated, (2) changing inspiratory flow rates. MATERIALS
      AND METHODS: Eight different HMEs were studied using a lung model system. The
      study was conducted initially by simulating spontaneous breathing, followed by
      connecting the system directly to a mechanical ventilator to provide pressure
      support ventilation. RESULTS: None of the encountered values of resistance
      (0.5?N3.6 cm H(2)O/L/s) exceeded the limits stipulated by the previously
      described international standard for HMEs (International Standards Organization
      Draft International Standard 9360-2) (not to exceed 5.0 cm H(2)O with a flow of
      1.0 L/s, even when saturated). The hygroscopic HME had less resistance than other
      types, independent of the precondition status (dry or saturated) or the
      respiratory mode. The hygroscopic HME also had a lesser increase in resistance
      when saturated. The resistance of the HME was little affected by increases in
      flow, but saturation did increase resistance in the hydrophobic and
      hygroscopic/hydrophobic HME to levels that could be important at some clinical
      conditions. CONCLUSIONS: Resistance was little affected by saturation in
      hygroscopic models, when compared to the hydrophobic or hygroscopic/hydrophobic
      HME. Changes in inspiratory flow did not cause relevant alterations in
      resistance.

PMID- 15871759
TI  - Diagnosis of cystic fibrosis and celiac disease in an adult: one patient, two
      diseases, and three reminders.
AB  - This case report describes the uncommon occurrence of celiac disease and cystic
      fibrosis in an obese adult patient. Apart from its rarity, the case serves to
      highlight the elusive nature of these 2 diseases when presenting with atypical
      clinical features in an adult.

PMID- 15871761
TI  - An overview of approaches to adjuvant therapy for colorectal cancer in the United
      States.
AB  - Adjuvant chemotherapy for colon cancer and combined chemotherapy and radiation
      therapy (RT) for rectal cancer increases the proportion of patients cured of
      their disease. Adjuvant chemotherapy is indicated for stage III colon cancer, and
      although controversial for stage II disease, there is evidence to suggest that
      these patients may benefit as well. Adjuvant chemotherapy and RT is recommended
      for patients with stage II/III rectal cancer. Studies incorporating oral
      fluoropyrimidines as well as combination chemotherapy have been completed, with
      results demonstrating the value of these approaches. A new generation of studies
      will evaluate the biologic agents bevacizumab and cetuximab in the adjuvant
      therapy of colorectal cancer. For rectal cancer, optimal outcomes are dependent
      not only on the systemic therapy, but also on the expertise of the surgeon and
      the timing of RT, with improved local control and toxicity seen with preoperative
      therapy.

PMID- 15871762
TI  - Epidermal growth factor receptor as a target for chemotherapy.
AB  - The epidermal growth factor receptor (EGFR) is overexpressed in as many as 77% of
      colorectal cancer (CRC) cases. The EGFR is known to be involved in carcinogenetic
      processes such as cell proliferation, apoptosis, angiogenesis, cell motility, and
      metastasis. Preclinical and clinical studies have shown that targeting EGFR is a
      valid strategy for anticancer therapy. Currently, 2 classes of anti-EGFR agents
      are in phase II/III clinical development: monoclonal antibodies and tyrosine
      kinase (TK) inhibitors. The most established monoclonal antibody is cetuximab,
      the only EGFR inhibitor that is currently approved for use in patients with
      metastatic CRC. Several clinical studies of cetuximab, as a single agent or in
      combination with irinotecan, have shown promising efficacy in patients with
      metastatic CRC. Two other monoclonal antibodies, matuzumab (EMD 72000) and
      panitumumab (ABG-EGF), also have shown activity against EGFR-expressing CRC but
      are still in the early stage of clinical development. The activity of the EGFR TK
      inhibitors erlotinib and gefitinib have already been investigated in clinical
      phase III trials in patients with non-small-lung cancer, suggesting that
      sequential rather than concurrent erlotinib/gefitinib-based treatment provides a
      benefit in clinical outcome. The EGFR-targeting agents are reasonably well
      tolerated and have limited overlapping toxicities in combination with other
      cytotoxic drugs. The most common side effect of anti-EGFR treatment is an
      acneiform skin rash, which is associated with the clinical outcome of treatment
      with monoclonal antibodies and TK inhibitors. Future clinical studies are needed
      to establish these EGFR-targeting agents in anticancer treatment to investigate
      efficacy of therapies combining EGFR-targeted agents with other targeting agents
      and to describe additional markers determining the clinical outcome of anti-EGFR
      therapy.

PMID- 15871763
TI  - Cetuximab in previously treated colorectal cancer.
AB  - Within the past decade, there have been considerable advances in the first- and
      second-line treatment of colorectal cancer (CRC). For many years, 5-fluorouracil
      was the only therapeutic option for the first-line treatment of CRC, and
      virtually no effective salvage therapies were available. However, the advent of
      oxaliplatin and irinotecan has improved outcomes for advanced CRC, providing
      increased therapeutic choice in the first-line setting and effective salvage
      therapies. Many patients are now receiving multiple lines of therapy, and it is
      in the setting of previously treated CRC that cetuximab, a monoclonal antibody to
      the epidermal growth factor receptor, has been successfully developed based on
      sound scientific principles. The ability to integrate new biologic therapies with
      conventional cytotoxic agents marks a new treatment era for this disease. This
      review discusses the development of cetuximab in pretreated CRC to date and
      future directions with this novel therapy.

PMID- 15871765
TI  - Clinical management of oxaliplatin-associated neurotoxicity.
AB  - In recent years, oxaliplatin-based chemotherapy protocols, particularly
      oxaliplatin in combination with infusional 5-fluorouracil/leucovorin (FOLFOX or
      FUFOX), have emerged as the standard of care in first- and second-line therapy of
      advanced-stage colorectal cancer. Although oxaliplatin by itself has only mild
      hematologic and gastrointestinal side effects, its clinically dominating toxicity
      affects the peripheral sensory nervous system in the form of 2 distinct types of
      neurotoxicity: (1) a unique, frequent, acute sensory neuropathy that is triggered
      or aggravated by exposure to cold but at the same time is rapidly reversible
      without persistent impairment of sensory functions; (2) the dose-limiting
      toxicity of oxaliplatin, a cumulative, chronic sensory neurotoxicity that
      resembles that of cisplatin with the important difference of its being more
      rapidly and completely reversible. This chronic sensory neurotoxicity is highly
      predictable, being closely associated with the cumulative dose of oxaliplatin
      that is administered. Various strategies have been proposed to prevent or treat
      oxaliplatin-induced neurotoxicity. The stop-and-go concept uses the
      predictability and reversibility of neurologic symptoms to allow patients to stay
      on an oxaliplatin-containing first-line therapy for a prolonged period. Several
      neuromodulatory agents such as calcium-magnesium infusions; antiepileptic drugs
      like carbamazepine, gabapentin, and venlafaxine; amifostine; a-lipoic acid; and
      glutathione have demonstrated some activity in the prophylaxis and treatment of
      oxaliplatin-induced acute neuropathy. However, randomized trials demonstrating a
      prophylactic or therapeutic effect on oxaliplatin's cumulative neurotoxicity are
      still lacking. The predictability of neurotoxicity associated with oxaliplatin
      based therapy should allow patients and doctors to develop strategies to manage
      this side effect in view of the individual patient's clinical situation. This is
      of increasing importance, because the addition of bevacizumab to FOLFOX will
      conceivably further prolong the progression-free survival achieved with FOLFOX so
      that neurotoxicity and not tumor progression could become the dominating
      treatment-limiting issue in the first-line therapy of advanced colorectal cancer.

PMID- 15871764
TI  - Irinotecan-based regimens in the adjuvant therapy of colorectal cancer.
AB  - Irinotecan is a cornerstone drug in the management of metastatic colorectal
      cancer, as demonstrated by several randomized studies proving a survival benefit
      for the first time. In the adjuvant setting, FOLFOX (infusional 5-fluorouracil [5
      FU]/leucovorin [LV] in combination with oxaliplatin) has improved 3-year disease
      free survival in stage II/III colorectal cancer in the MOSAIC trial. Because 5
      FU/LV-based combination therapy with oxaliplatin or irinotecan has similar
      efficacy in metastatic disease in the first-line setting, the impact of
      irinotecan in the adjuvant setting deserves further randomized clinical trials.
      Six such trials are ongoing or have already been closed to accrual, the results
      of which will be reported shortly. Five of these trials presently accruing
      patients or already closed combine irinotecan with an infusional regimen of 5-FU,
      based on a better tolerance and efficacy profile established in the metastatic
      setting according to clinical trials conducted principally in Europe. The results
      of 2 main randomized trials in the adjuvant therapy of stage III colon cancer
      will be presented at the 41st Annual Meeting of the American Society of Clinical
      Oncology in 2005 and are eagerly awaited. These results should provide important
      new insights as to how to manage stage II/III colon cancer.

PMID- 15871766
TI  - Benefits and drawbacks of the use of oral fluoropyrimidines as single-agent
      therapy in advanced colorectal cancer.
AB  - One of the most widely used cytotoxic agents is 5-fluorouracil. The use of
      infusional regimens has become commonplace and with this has come a realization
      of the limitations of this mode of administration. A number of oral
      fluoropyrimidines have been developed. Of these, capecitabine is the most
      established, with registrations in most countries for breast and colorectal
      cancer. The trials with this agent have mainly attempted to show equivalence with
      a "standard" intravenous comparator. In most cases, this endpoint has been met or
      exceeded. In addition, the trials have demonstrated reduced toxicity (except for
      hand-foot syndrome), and aspects of patient acceptability and cost-effectiveness
      have been integrated into these studies. Patients seem to prefer oral therapy but
      not at the expense of anticancer activity. However, the absence of intravenous
      access devices and complications associated with their use is a major bonus for
      oral therapy. The drawbacks are somewhat less obvious. Some patients are
      concerned that oral therapy is in some way inferior (ie, soft option) to
      intravenous chemotherapy. Compliance with oral therapy is always questionable.
      Although very few trials in which compliance has been formally assessed have been
      performed, the issue of overcompliance has not been addressed; in other words,
      there may be a problem of patients continuing to take the medication even in the
      face of toxicity and advice to stop treatment. Oral chemotherapy requires just as
      much care as intravenous chemotherapy and probably requires more attention to
      patient education and involvement in care decisions.

PMID- 15871767
TI  - Determinants of patient and surgeon perspectives on maximum acceptable waiting
      times for hip and knee arthroplasty.
AB  - OBJECTIVES: Lengthy waiting times for hip and knee arthroplasty have raised
      concerns about equitable and timely access to care. The Western Canada Waiting
      List project has developed priority criteria scores linked to maximum acceptable
      waiting times (MAWT) for different levels of priority. Our study purpose was to
      assess the determinants of patient- and surgeon-rated MAWT, and to test whether
      the anticipated waiting time has an independent influence after adjusting for
      age, sex and patient urgency. A second aim was to compare MAWT, waiting time and
      anticipated waiting time for different levels of urgency assessed using the
      priority criteria score. METHODS: Orthopaedic surgeons assessed 233 consecutive
      patients waiting for arthroplasty in terms of their urgency (assessed using the
      priority criteria score and a visual analogue scale), MAWT and anticipated
      waiting time. Patient data included urgency (assessed by a visual analogue
      scale), MAWT and the Western Ontario McMaster Osteoarthritis index. We used
      hierarchical linear regression to test the models. RESULTS: After adjusting for
      age and sex, urgency (assessed by priority criteria score and visual analogue
      scale) and anticipated waiting time accounted for 40% of the variance in surgeon
      MAWT. The patient model accounted for 30% of the variance in patient MAWT. Older
      patients preferred signficantly shorter MAWTs (P <0.05). Anticipated waiting time
      added significantly to both the surgeon and patient MAWT models (R(2) change 0.11
      and 0.07, respectively). Actual waiting time was weakly correlated with urgency
      assessed using the priority criteria score (r = -0.25, P <0.0001). CONCLUSIONS:
      Patients' and surgeons' views are critical to a fair process of establishing MAWT
      for elective procedures. Anticipated waiting time may influence the perspectives
      on MAWT and must be considered in their interpretation.

PMID- 15871769
TI  - (Mis)Interpretations of leukoplakia.

PMID- 15871770
TI  - Development and testing of an audio-visual aid for improving infant oral health
      through primary caregiver education.
AB  - PURPOSE: To create and test an audio-visual (AV) aid for providing anticipatory
      guidance on infant oral health to caregivers. METHODS: A DVD-video containing
      evidence-based information about infant oral health care and prevention in
      accordance with the American Academy of Pediatric Dentistry guidelines has been
      developed (www.utoronto.ca/dentistry/newsresources/kids/). It contains
      comprehensive anticipatory guidance in the areas of pregnancy, oral development,
      teething, diet and nutrition, oral hygiene, fluoride use, acquisition of oral
      bacteria, feeding and oral habits, causes and sequelae of early childhood caries,
      trauma prevention, early dental visits and regular dental visits. A questionnaire
      was developed to test the knowledge of expectant and young mothers (n = 11) and
      early childhood educators (n = 16) before and after viewing the video. RESULTS: A
      significant lack of knowledge about infant oral health was indicated by the
      proportion of "I don"t know" (22%) and incorrect (19%) responses to the
      questionnaire before the viewing. Significant improvement in knowledge (32%;
      range -3% to 57%; p < 0.001) was indicated by the proportion of correct responses
      (91%) following a single viewing of the AV aid. CONCLUSION: This AV aid promises
      to be an effective tool in providing anticipatory guidance regarding infant oral
      health in high-risk populations. Unlike existing educational materials, this aid
      provides a comprehensive, self-directed, evidence-based approach to the promotion
      of infant oral health. Widespread application of this prevention protocol has the
      potential to result in greater awareness, increased use of dental services and
      reduced incidence of preventable oral disease in the target populations.

PMID- 15871771
TI  - Financing and delivering oral health care: what can we learn from other
      countries?
AB  - In Canada, the delivery of dental care is left largely to private markets; public
      funding is limited to targeted groups of the population and substantial variation
      between provinces exists. In this article, the levels and sources of expenditures
      on dental care, the levels and distribution of service use associated with these
      expenditures and the oral health outcomes "produced" in Canada are considered in
      an international context. The international trend toward an increasing share of
      public funds for dental care expenditures is not observed in Canada. Instead an
      increasing reliance on private funds is associated with greater barriers to care,
      particularly among less prosperous groups. In the absence of oral health data at
      the national level, the impact of these trends on oral health outcomes is
      unknown. Several key messages are identified in the comparative analysis to
      inform any future oral health strategy for Canada.

PMID- 15871772
TI  - Medicolegal aspects of replanting permanent teeth.
AB  - Replantation of a permanent tooth is an intervention that carries the same
      responsibilities in terms of informed consent as a surgical procedure. Unlike
      many procedures that can be planned in advance, an avulsion requires decision
      making shortly after the injury, often by a distraught patient or parent. Under
      these circumstances, patients or parents prefer, or may even pressure, clinicians
      to make the replantation decision for them.Later, the parents may seek advice of
      other professionals or be confronted by lay opinions or Internet information that
      may lead them to doubt the decision or even feel betrayed by the dentist who
      provided the acute care. This article uses an actual parent complaint to
      illustrate the medicolegal aspects of the replantation decision and describe
      measures to be taken by the clinician faced with this situation.

PMID- 15871773
TI  - Adenomatoid odontogenic tumour: review and case report.
AB  - Adenomatoid odontogenic tumour is a benign (hamartomatous), noninvasive lesion
      with slow but progressive growth. The 3 variants--follicular, extrafollicular and
      peripheral--present with identical histological findings. This report describes a
      patient with a large adenomatoid odontogenic tumour in the mandible, with the
      involved mandibular canine being pushed to the contralateral side. The paper also
      provides a refresher for general dental practitioners about various diagnostic
      aspects of this tumour and highlights the controversies regarding its origin and
      management in light of recent findings.

PMID- 15871774
TI  - Forced orthodontic eruption of fractured teeth before implant placement: case
      report.
AB  - The treatment of esthetic areas with single-tooth implants represents a new
      challenge for the clinician. Placement of a single-unit implant is indicated for
      fractured or periodontally compromised teeth. In 1993, a modification of the
      forced eruption technique, called "orthodontic extrusive remodelling," was
      proposed as a way to augment both soft- and hard-tissue profiles at potential
      implant sites. This case report describes augmentation of the coronal soft and
      hard tissues around a fractured tooth, which was achieved by forced orthodontic
      extrusion before implant placement. This technique may be used to improve primary
      anchorage of a dental implant, fill the alveolar socket with bone, preserve
      interdental bone height and increase the amount of attached gingiva.

PMID- 15871775
TI  - [Genotypic resistence in patients infected with HIV and its correlation with
      therapy].
AB  - BACKGROUND AND OBJECTIVE: Our goal was to establish the different therapeutic
      regimens used in our clinical setting, and to determine the prevalence of
      genotypic resistances in patients under antiretroviral therapy, analyzing the
      relationship between the appearance of mutations and treatments along with other
      HIV related variables. MATERIAL AND METHOD: 191 samples from the same number of
      patients who were on antiretroviral therapy and virological failure were
      analyzed. Samples were processed by means of the genotypic technique LiPA in
      order to study the presence of mutations in the reverse transcriptase (RT) and
      the protease (P) genes. Prescribed therapeutic regimens and epidemiological
      variables relevant in HIV infection were also analyzed. RESULTS: Overall
      resistance prevalence was 72.32%. By LiPA, RT mutations were detected in 71.43%
      of patients, being M184V, T215Y and L41M the most frequent ones. Moreover, P
      mutations were detected in 59.38% of cases, being V82A, L90M and I84V the most
      frequent ones. 61.02% of the patients presented one or more mutations against the
      reverse transcriptase inhibitors included in their treatment. With regard to
      protease inhibitors, this fact was documented in 28.81% of cases, and in 23.73%
      of patients receiving both reverse transcriptase inhibitors and protease
      inhibitors. CONCLUSIONS: Although the analysis of the mutation patterns by LiPA
      has known limitations, the prevalence of resistances in our study was different
      from that reported by other authors, being lower in the P gene and higher in the
      RT one. Of note, a high proportion of patients showed mutations against the drugs
      included in their prescribed treatment.

PMID- 15871776
TI  - [Cardiovascular risk factors in Spanish population: metaanalysis of cross
      sectional studies].
AB  - BACKGROUND AND OBJECTIVE: To review published studies on the prevalence of the
      main vascular risk factors -hypertension, hypercholesterolemia, diabetes
      mellitus, obesity and tobacco smoking- in Spain, and to combine their results in
      an estimate for the Spanish population. MATERIAL AND METHOD: After a
      bibliographic search, the studies fulfilling the following inclusion criteria
      were selected: cross-sectional design, sampling on Spanish population, results
      including prevalence data of at least one of the above mentioned risk factors,
      and objective [corrected] (not self-referred) determination of arterial blood
      pressure, total serum cholesterol, basal glucose, weight, size and body mass
      index. The combined prevalence was obtained by means of the random effects model,
      including weight for the proportion that the studied population supposes on the
      total Spanish population. RESULTS: Forty-eight studies were identified including
      a total of 130.945 subjects. According to these studies, the most frequent
      vascular risk factors were hypertension in the elderly (66.7%, CI 59-74%),
      overweight/obesity in adult women (48,3%, CI 41-55%) and smoking among men
      (41.1%, CI 38-44%). In the Spanish population as a whole, 23% showed total
      cholesterol levels above 250 mg/dl; 33% were smokers (41,1% in men and 24% in
      women); 34% suffered hypertension; 20% were obese (18% in men and 23% in women);
      and diabetes affected 8% women and 12% men. CONCLUSION: Cardiovascular risk in
      Spain is high. Monitoring the vascular risk factors at a population level is
      basic for preventive and health care measures.

PMID- 15871777
TI  - [Continuous enteral nutrition versus single bolus: effects on urine C peptide and
      nitrogen balance].
AB  - BACKGROUND AND OBJECTIVE: Our study was designed to assess the impact on nitrogen
      and glucose metabolism when it is administered either as discontinuous or as
      continuous infusion. PATIENTS AND METHOD: We assessed the nutritional efficacy
      (nitrogen balance) and hyperinsulinism risk (urine C peptide excretion) of
      enteral nutrition in 23 patients hospitalized because of acute stroke. RESULTS:
      The feeding tolerance of our enteral nutrition protocol (nasoenteric catheter)
      was full in every patient. The nitrogen balance was positive in both patterns,
      but the balance in the continuous feeding pattern was better than in the bolus
      feeding one. On the contrary, the urine C peptide excretion was increased when
      enteral nutrition was administered intermittently as compared with continuous
      feeding. Calciuria was greater in the continuous fed pattern than in the bolus
      feeding. CONCLUSIONS: Continuous feeding is associated with better nitrogen
      balance and less urine C peptide excretion than intermittent feeding. These
      results suggest that continuous feeding would be an interesting choice to improve
      glucose control in diabetic patients with enteral nutrition.

PMID- 15871779
TI  - [Mutations resulting in resistence of antiretroviral drugs in HIV-infected
      patients].

PMID- 15871778
TI  - [Current status of HIV-2 and HTLV-1/2 infection in Spain: lights and shades].

PMID- 15871780
TI  - [Conventional hospitalization alternatives in internal medicine].

PMID- 15871781
TI  - [Assessing the implementation of the VisualCor software in medical practice].

PMID- 15871782
TI  - [Neurological manifestations of the antiphospholipid syndrome].
AB  - Antiphospholipid syndrome can be associated with several neurological
      manifestations. The most common symptom is headache. It has also been associated
      with cognitive dysfunction, probably due to ischemia. A high prevalence of
      antiphospholipid antibodies has been found in patients with epilepsy and in
      transverse myelitis. The most common thrombotic manifestation is stroke. Venous
      thrombosis can also be found, yet it is less frequent. A stroke in a young person
      obliges to rule out the antiphospholipid syndrome. The neurological
      manifestations can mimic multiple sclerosis. Thus, determination of
      antiphospholipid antibodies is recommended in the study of patients with atypical
      manifestations of multiple sclerosis. Other manifestations associated with
      antiphospholipid antibodies include chorea, neurosensorial deafness, Guillain
      Barre syndrome, and psychotic disorders.

PMID- 15871783
TI  - [Treatment of severe hypertension during pregnancy].

PMID- 15871784
TI  - [Weight loss with topiramate in patients with epileptic disorders].

PMID- 15871785
TI  - [Cardiovascular risk and HIV-infection in prison inmates].

PMID- 15871786
TI  - [Prediction of the clinical manifestations in Lesch-Nyhan disease].

PMID- 15871787
TI  - [Inhalation hair sprays: a dangerous addiction?].

PMID- 15871788
TI  - [Clinical trial registration: new ICMJE requirement].

PMID- 15871789
TI  - [Linezolid-related leukocytoclastic vasculitis].

PMID- 15871791
TI  - [Care for patients at the end of their lives].

PMID- 15871792
TI  - [Peoples Doctor. Jordi Gol i Gurina, 1924-1985, in memoriam].

PMID- 15871793
TI  - [Prevalence of osteopenia and osteoporosis in postmenopausal women].
AB  - OBJECTIVE: To know the osteoponia and osteoporosis prevalence in postmenopausal
      women determined with broadband ultrasonic attenuation (BUA). DESIGN:
      Descriptives cross-sectional study of prevalence. SETTING: Salvador Allende
      Health Center. Valencia, Spain. PARTICIPANTS: A total of 115 postmenopausal women
      aged 49 at 85 years old was studied, initiated in September to December 2003.
      Iatrogenic menopause or women with calcium, vitamin D, estrogen replacement
      therapy, estrogen receptor modulators, and biphosphonates therapy were considered
      criteria for exclusion. We measured bone mineral density with BUA at right
      calcaneus. MAIN MEASUREMENTS: We analyzed the age, height, and weight, the result
      of BUA, tobacco and diuretics consumption and years of amenorrhea. RESULTS: . The
      prevalence of osteoporosis was 50.4%. Other 29.6% had osteopenia. Of the
      postmenopausal women with osteoporosis, 27.6% were 70 to 75 years old. The 82.8%
      of postmenopausal women with osteoporosis were younger than 75 years old. The
      66.7% postmenopausal women with body mass index lesser than 25 had osteoporosis.
      CONCLUSIONS: The osteoporosis prevalence in our patients was greater than other
      studies (30%). Emphasis may be placed on screening osteoporosis with BUA in
      primary health care. We suggested that educational community programs should
      start at an earlier age to identify factors that contribute to maintaining bone
      mineral density among postmenopausal women.

PMID- 15871794
TI  - [Is osteoporosis a prevalent problem in primary care?].

PMID- 15871795
TI  - [Use of oral lipid-lowering drugs in patients with type-2 diabetes mellitus].
AB  - OBJECTIVE: To investigate whether oral lipid-lowering drugs (OLL) are used in
      line with the Mexican Official Regulation (NOM)-015-SSA-1994 for preventing,
      treating, and monitoring diabetes mellitus 2 (DM2) patients. DESIGN:
      Observational, descriptive study. SETTING: Primary care. Unit of Family Medicine
      (UMF) No. 80 of the Mexican Social Security Institute. PARTICIPANTS: 332 patients
      diagnosed with DM2, taking pharmacological treatment and with recent laboratory
      studies. MAIN MEASUREMENTS: Age, body mass index (BMI), years of evolution of
      diabetes, type of medication and OLL dose, time taking OLL, glucose, total
      cholesterol, and triglycerides. The patients were divided into 2 groups on the
      basis of the BMI: group 1 with BMI<27; group 2 >=27. In addition, each group was
      sub-divided by the type of medication. RESULTS: Glibenclamide was the OLL most
      prescribed (52% in both groups). In group 1 there were significant intra-group
      differences between patient's age and years of evolution of diabetes, whereas in
      group 2 only the metformin sub-group was associated with lower glucose
      concentrations and higher concentrations of triglycerides than in the other sub
      groups. All patients had deficient glucaemia control. CONCLUSIONS: The data show
      that OLL treatment for DM2 patients varied from the NOM. Unification of criteria
      in primary care for the prescription pattern and the use of OLL for better
      metabolic control of this kind of patient were recommended.

PMID- 15871796
TI  - [Texas revised inventory of grief: adaptation to Spanish, reliability and
      validity].
AB  - OBJECTIVES: To adapt into Spanish the Texas Revised Inventory of Grief (TRIG) of
      Faschinbaguer et al (1977, 1981) and to examine its reliability and validity.
      DESIGN: Two stages: a) cross-culture adaptation of a questionnaire, and b) cross
      sectional study of reliability and validity. SETTING: Primary care teams in
      Vizcaya, north of Spain. PARTICIPANTS: 118 people who had been widowed between 3
      months and 3 years before the study. MAIN MEASUREMENTS AND RESULTS: Cross-culture
      adaptation: the TRIG was translated from American English, then back-translated
      and finally compared with the version in American Spanish by Grabowski & Frantz
      (1993). Reliability: the Cronbach's alpha coefficients (internal consistency) of
      the 2 TRIG scales were 0.75 and 0.86. Factorial validity: all items except one
      threw saturation >0.40 on the 2 factors extracted from the varimax rotation.
      Validity by hypothesis: the TRIG scales showed differences (P<.05) between the
      grieving in terms of the expected or unexpected character of death, the place
      where death occurred and time elapsed since the death. The scores on the adapted
      TRIG were similar to scores on the American Spanish TRIG for Latins and higher
      than those on the original TRIG and the American Spanish TRIG for Anglo-saxons.
      Convergent validity: the 2 TRIG scales correlated positively (P<.05) with all the
      clinical scales on the Inventory of Grief Experiences of Sanders et al (1985) and
      Garcia Garcia et al (2001). CONCLUSIONS: In the evaluation of grief due to the
      death of the spouse, the TRIG adapted to Spanish is as reliable and valid as the
      original version.

PMID- 15871797
TI  - [Prevalence of "hidden" renal failure in the population suffering from type-2
      diabetes].
AB  - OBJECTIVE: To determine the prevalence of renal failure (RF) in type-2 diabetics
      and to compare two criteria of definition: that based on the calculation of
      glomerular filtration by the Cockcroft-Gault formula corrected for body surface
      area and that based on serous creatinine. DESIGN: Cross-sectional, descriptive
      study. SETTING: El Cristo Health Centre, Oviedo, north of Spain. PARTICIPANTS:
      All patients in the catchment area diagnosed with type-2 diabetes. METHOD:
      Demographic, clinical, risk factor, and cardiovascular pathology details were
      gathered. Renal failure was diagnosed on figures of plasma creatinine >=1.3 mg/dL
      in women and >=1.4 mg/dL in men, and glomerular filtration (GF) calculated by
      means of the Cockcroft-Gault formula: moderate GF, 60-30 mL/min/1.73 m2; severe
      GF, 29-15 mL/min/1.73 m2, and terminal GF: <15 mL/min/1.73 m2. RESULTS: 499
      patients were included. 52.3% were women, aged 69.7+/-10.4 years old. Prevalence
      of RF by serous creatinine was 12%; and by the Cockcroft-Gault formula, 40.5%.
      Patients with lower glomerular filtration and normal creatinine were older
      (75.5+/-7.9 vs 65.4+/-9.8; P<.001), mainly female (76.3% vs 41.7%; P<.001), had
      lower BMI (27.3+/-3.7 vs 30.9+/-4.4) and had worse glucaemia control (HbA1c 7.1+/
      1.8% vs 6.9+/-1.9%; P=.007) and higher indices of cardiac failure (6.4% vs 2.1%;
      95% CI, 1.1-8.8; P=.02) than patients with normal glomerular filtration and
      creatinine. CONCLUSION: Calculation of glomerular filtration by the Cockcroft
      Gault formula corrected for body surface area revealed unknown renal failure in 1
      in 3 type-2 diabetes patients.

PMID- 15871798
TI  - [A stranger in the Congress. Ethnographic Evaluation of the XXIV Congress of
      Family and Community Medicine, Sevilla, 8-11 December 2004].

PMID- 15871799
TI  - [Clinical practice for medical students at health centres: teaching possibilities
      of the web at the Unit of Family Medicine and Primary Care of the Autonomous
      University of Madrid].

PMID- 15871800
TI  - [Study of the gastroscopies requested at a health centre].

PMID- 15871801
TI  - [Is the pharmaceutical industry necessary in the non-health care activities of
      primary care doctors?].

PMID- 15871802
TI  - [Prevalence of central obesity and obesity on the body mass index at a primary
      care centre].

PMID- 15871803
TI  - [Values and preferences of patients: question pending].

PMID- 15871805
TI  - [Teaching basic reanimation techniques to the general public].

PMID- 15871806
TI  - [Intravenous administration of vitamin B12a in cases of cyanide poisoning].

PMID- 15871807
TI  - [Complications of endoscopic retrograde cholangiopancreatography in patients aged
      more than 90 years old].
AB  - INTRODUCTION: To evaluate the effectiveness of endoscopic retrograde
      cholangiopancreatography (ERCP) and the complication rates of this procedure in
      patients aged 90 years and older. PATIENTS AND METHOD: A descriptive, prospective
      study including 42 endoscopic procedures performed from first January 2001 until
      first June 2004 in 36 patients (7 males and 29 females) was performed. The mean
      age was 91 years (range 90-96 years). All patients underwent the following: a)
      clinical evaluation before and after endoscopic exploration; b) evaluation of the
      success or failure of the endoscopic procedure and c) assessment of complications
      (perforation, hemorrhage, pancreatitis and infection). Concurrent associated
      illnesses, as well as the existence of anatomical alterations in Vaters papilla
      (duodenal diverticula), were also evaluated. RESULTS: ERCP was successful in
      85.7% of all explorations performed. Twenty-three patients (63.8%) had one or
      more major associated diseases. In 15 patients (33.3%) Vaters papilla was
      associated with duodenal diverticula. The complication rates were as follows: 1)
      acute pancreatitis in 2 explorations (4.7%), one mild (2.35%) and the other
      moderate (2.35%); 2) hemorrhage after endoscopic sphincterotomy in 2.8% of
      patients (1/35); 3) bacteriemia in one patient (2.3%) and cholangitis in one
      patient (2.3%), with no cases of secondary cholecystitis; 4) hypoxemia in one
      patient. There were no perforations or deaths related to the procedure.
      CONCLUSION: ERCP is a safe and effective technique with a low complication rate
      in patients aged 90 years or older.

PMID- 15871809
TI  - [Ductal regeneration in vanishing bile duct syndrome in Hodgkin's lymphoma].
AB  - We present the case of a 17-year-old male patient with Hodgkin's lymphoma
      (nodular sclerosis) in the mediastinum. During the postoperative period treatment
      with erythromycin was started and the patient developed progressive jaundice and
      cholestasis. Treatment modified for the lymphoma was initiated, which achieved
      complete remission and subsequent improvement and resolution of the cholestasis.
      Histological study of the liver revealed massive loss of bile ducts. After
      resolution of the cholestasis, consecutive biopsies revealed ductal
      proliferation. The present report therefore illustrates a case of ductopenia or
      vanishing bile duct syndrome (VBDS) with ad integrum regeneration of the bile
      ducts simultaneous with lymphoma remission. Because the 2 possible causes,
      erythromycin toxicity and Hodgkin's lymphoma, occurred simultaneously, the
      etiology of the VBDS cannot be definitively established.

PMID- 15871808
TI  - [Persistence of a magic-religious ritual to treat indigestion among patients
      attending a gastroenterology outpatient clinic].
AB  - INTRODUCTION: Knowledge of popular medicine is essential to the practice of
      integrated medicine. Empacho (stomach upset) is a known folk illness that has
      been the object of several studies, especially in Iberoamerica and among the
      Hispanic population in the United States. In the Autonomous Community of Valencia
      (Spain) a magic-religious ritual known as "trencar lenfit" (TE) is still
      performed. This ritual has no apparent equivalent among the numerous remedies
      described for this illness. OBJECTIVES: To study the frequency and
      characteristics of the practice of TE among patients attending the
      gastroenterology outpatient clinic of a district hospital. PATIENTS AND METHOD:
      The geographical area was the region of La Safor (Valencian Community) with three
      main nuclei (Gandia, where the hospital is situated, Oliva and Tavernes de
      Valldigna) and 28 smaller municipalities. Random interviews were performed in
      patients attending a second consultation over a period of 5 months. RESULTS: Of
      539 patients interviewed, 320 (59.4%) had undergone TE at some time in their
      lives and 25.0% had undergone this ritual in the previous 10 years. In 95.9% of
      cases, the person performing the ritual was a woman. Of the patients who had
      undergone TE, 40 (12.5%) knew how to perform the ritual, 35 of which were women
      (p < 0.0001). No significant differences were found between sexes but users were
      younger (51.8 +/- 15.9 versus. 55.5 +/- 17.7 years +/- SD, p < 0.05). Small
      municipalities and Oliva showed a frequency of 65.6% versus. 54.0% in Gandia and
      Tavernes (p < 0.005). Use was greater among natives of the Valencian Community
      (66.0%) compared with those from other parts of Spain (25.0%) (p < 0.0001).
      Patients who completed primary or secondary school showed greater use of TE
      (60.5% and 72.1%, respectively) than the illiterate (42.1%), those who had
      completed a 3-year higher education course (48.4%) and university graduates
      (36.0%) (p < 0.001). TE was more frequent among consumers of medicinal herbs than
      among non-consumers (69.0% versus. 54.3%) (p < 0.001). No relationship was found
      among TE and the use of alcohol, medication in general and smoking. However, an
      association was found between the use of psychotropic drugs (69.8% versus. 55.4%)
      (p < 0.005). No clear association was found with broad diagnostic group or with
      the functional/organic nature of the digestive disorder studied. Variables found
      to be significant on univariate analysis remained significant in multivariate
      analysis (logistic regression). CONCLUSION: The present study confirms the high
      use of TE among patients attending the gastroenterology outpatient clinic of La
      Safor and their belief in this ritual. "Experts" in performing TE were widely
      available, and were almost exclusively women. The profile of maximal use of TE
      corresponds to a man or woman, aged less than 60 years, a native of the Valencian
      Community, with primary or secondary school education, residing in particular
      municipalities (usually small) and consumer of psychotropic drugs and medicinal
      herbs.

PMID- 15871810
TI  - [Utility of Tc-99m labeled heat-denatured red blood cell scintigraphy in a case
      of hepatic splenosis].
AB  - The term splenosis, first used in the medical literature in 1939, refers to the
      autotransplantation of splenic tissue in a heterotopic location. We report the
      case of a known hepatitis C carrier in whom computed tomography scanning revealed
      a hepatic lesion suggestive of hepatocarcinoma. Magnetic Resonance imaging was
      performed for suspected hepatic splenosis, which was confirmed by Tc-99m labeled
      heat-denatured red blood cell scintigraphy. In addition to confirming the
      suspected diagnosis, this technique showed several pathological foci in distinct
      abdominal locations compatible with splenosis that had not previously been
      identified.

PMID- 15871811
TI  - [Autoimmune hemolytic anemia associated with ulcerative colitis].
AB  - The incidence of immunological disorders has been reported to be greater in
      patients with inflammatory bowel disease than among the general population. The
      association of ulcerative colitis (UC) and autoimmune hemolytic anemia (AIHA) was
      first described in the early 1950s but no more than 50 cases have been described
      in the international literature. Detailed description of the pathogenic
      mechanisms involved in this association is lacking. The clinical course of AIHA
      and treatment response in these patients seems to be independent of UC, sometimes
      requiring immunosuppressive treatment and even surgery. We present 2 cases of
      AIHA associated with UC with distinct response to conventional treatment. We also
      review the literature on the subject.

PMID- 15871812
TI  - [Cecal cytomegalovirus infection following appendicectomy in a patient with
      ulcerative colitis].
AB  - We report a patient who, 3 months after being diagnosed with ulcerative colitis,
      was admitted to hospital because of malaise and right lower abdominal pain. An
      open appendectomy was performed. Histological study showed ulcerative colitis
      affecting the appendix. After surgery, the patient presented a refractory
      outbreak of ulcerative colitis requiring treatment with steroids and cyclosporin
      A. Despite this treatment, the patient continued to pass abundant fresh blood
      associated with severe anemia. Colonoscopy showed only granular and congestive
      cecal mucosa. Biopsies showed intracytoplasmic inclusion bodies with
      immunohistochemical stains positive for cytomegalovirus (CMV) infection.
      Rectorrhagia and anemia quickly disappeared after beginning treatment with
      ganciclovir. Appendicular ulcerative colitis is not uncommonly associated with
      distal colitis. In addition, diffuse CMV infection complicating ulcerative
      colitis treatment is not unusual. By contrast, isolated, segmentary infection by
      CMV in the proximal colon is extremely rare. Until now, only three patients with
      localized CMV infection have been described, and all three cases occurred in the
      context of ileoanal anastomosis.

PMID- 15871813
TI  - [Capsule endoscopy and inflammatory bowel disease].

PMID- 15871814
TI  - [Early diagnosis of liver cancer].
AB  - Hepatocellular carcinoma is a frequent neoplasm that usually develops in patients
      with liver cirrhosis. Because it is the main cause of death in these patients,
      they should be included in a surveillance program in order to identify these
      tumors at an early stage and be able to indicate curative treatment (liver
      transplantation, surgical resection or percutaneous ablation therapy) and to
      reduce mortality. Surveillance should include determination of alpha-fetoprotein
      and abdominal ultrasound every 6 months. This strategy should only be applied to
      patients suitable to receive curative treatment if diagnosed of hepatocellular
      carcinoma. Using this approach, 40-80% of tumors identified are solitary at
      diagnosis, although only half of these patients can benefit from curative
      treatment.

PMID- 15871815
TI  - [Advantages of computerized management in a gastrointestinal endoscopy unit].
AB  - Computerized management of the activity of a gastrointestinal endoscopy unit in a
      hospital requires technological resources that include an intrahospital network,
      a computerized endoscopy program, a computerized appointments program and
      electronic medical records. The endoscopy unit should define the portfolio of
      services it provides and establish the time required to perform each procedure,
      probably using distinct criteria for outpatient and inpatient requests.
      Computerized management should establish forms designed to receive, accept and
      schedule requests, and should transfer all the contents of the request to the
      endoscopy program. The endoscopy program makes and stores reports and images.
      Integration among the programs allows these contents to be transferred to the
      electronic medical record. Measures to guarantee the confidentiality and safety
      of the medical information in each center should be implemented in accordance
      with its policy on access to medical information.

PMID- 15871816
TI  - [Barotrauma with rectal laceration due to compressed air].

PMID- 15871817
TI  - [Toxic hepatitis induced by Chinese herbs].

PMID- 15871818
TI  - [Tumoral markers in liver cirrhosis and hepatocellular carcinoma].

PMID- 15871819
TI  - [Autoimmune hepatitis associated with Crohn's disease and cytoplasmic
      antineutrophilic cytoplasmic antibodies].

PMID- 15871820
TI  - [Utility of echoendoscopy for endoscopic resection of duodenal carcinoid tumors].

PMID- 15871821
TI  - [Palliative care in the intensive care unit].

PMID- 15871823
TI  - [Mortality from cancer in children and adolescents in Madrid, 1977-2001].
AB  - INTRODUCTION: In the last few decades mortality from cancer among children and
      adolescents has not decreased homogeneously in industrialized countries. The aim
      of this study was to determine the epidemiological pattern and temporal trend of
      mortality from cancer in individuals aged less than 20 years old living in the
      Autonomous Community of Madrid from 1977 to 2001. MATERIAL AND METHODS: Data on
      deaths from cancer among children and adolescents were obtained from Spain's
      National Institute of Statistics and from the Mortality Registry of Madrid.
      Populations were obtained from official publications of the Institute of
      Statistics of Madrid. Variables analyzed were sex, 5-year age groups, 5-year
      death periods and underlying cause of death. The epidemiological pattern was
      studied and a Poisson's regression model was used to analyze cancer mortality
      trends in children and adolescents from 1977 to 2001. RESULTS: Cancer mortality
      among children and adolescents decreased by 41 % from 1977 to 2001. The decrease
      in mortality differed according to sex (46 % in boys and 33 % in girls) and type
      of cancer (leukemias: 38 %, non-Hodgkin's lymphomas: 58 %, malignant brain
      tumors: 45 %, malignant bone tumors: 19 %, ill-defined malignant tumors: 78 %).
      Moreover, the annual decrease was much greater in the last 5 years (4. 7 %) than
      during the entire period (2. 2 %). CONCLUSIONS: Cancer mortality among children
      and adolescents decreased between 1977 and 2001 and our results are similar to
      those observed in other European and North American regions. To improve knowledge
      of the epidemiology of cancer among children and adolescents in the Autonomous
      Community of Madrid, future assessments including mortality, incidence, and
      survival indicators are required.

PMID- 15871822
TI  - [Serological and genetic markers in the diagnosis and follow-up of coeliac
      disease].
AB  - INTRODUCTION: Understanding of celiac disease has changed with the advent of
      serological markers (antigliadin IgA, anti-endomysial IgA and anti
      transglutaminase IgA antibodies) and with the identification of major
      susceptibility genes (HLA-DQA1*05-DQB1*02). Reports of the efficacy of these
      diagnostic tests have varied, depending on the methodology used and the
      population investigated. OBJECTIVES: To determine the clinical utility of genetic
      and serological markers in the diagnosis of celiac disease, their relationship
      with histological lesions and their changes during treatment, in order to
      establish an optimal diagnostic algorithm in our environment. PATIENTS AND
      METHODS: We performed a retrospective study of 590 patients from the health area
      of Badajoz referred to the Immunology Laboratory for screening or follow-up of
      celiac disease. The results of intestinal histology, serological markers
      (antigliadin IgA, anti-endomysial IgA and anti-transglutaminase IgA antibodies),
      and genomic typing (HLA-DQA1*05-DQB1*02) were analyzed. RESULTS: The sensitivity
      and specificity of serological tests were greater than 90 %, with a negative
      predictive value of 98-100 %. HLA-DQA1*05-DQB1*02 was detected in 97 % of celiac
      patients, with a very high negative predictive value (99 %). On biopsy, 95 % of
      the patients with some grade of intestinal lesion were positive for antigliadin
      and/or anti-endomysial antibodies. CONCLUSION: To avoid missed diagnoses, the
      diagnostic algorithm of celiac disease should include at least two serological
      markers (antigliadin antibodies and anti-endomysial and/or anti-transglutaminase
      antibodies) and IgA quantification. Genomic typing should be carried out if one
      or more markers are positive or if the subject belongs to any of the risk groups.
      The physician should decide on the advisability of intestinal biopsy on the basis
      of the patient's clinical and immunological history.

PMID- 15871824
TI  - [Intrapleural urokinase in the treatment of parapneumonic effusions].
AB  - INTRODUCTION: Intrapleural fibrinolytic instillation has been used in the
      treatment of loculated pleural effusions and empyemas and has reduced the need
      for surgical intervention. Currently, the most commonly used fibrinolytic is
      urokinase, although the doses have not yet been standardized in children. The aim
      of the present study was to evaluate the utility of urokinase in the treatment of
      infectious pleural effusions in children. MATERIAL AND METHODS: A retrospective
      study was performed of children with infectious pleural effusions admitted to the
      pediatric intensive care unit (PICU) between January 2000 and December 2003. Age,
      sex, clinical features, laboratory tests, response to urokinase treatment and
      clinical course during hospital stay were analyzed. RESULTS: Thirty-one children
      were treated. The mean age was 38.1 months (SD: 22). There were 18 boys and 13
      girls. The most frequent month of diagnosis was November and the number of
      admission significantly increased from 2002 onwards. The most frequent antibiotic
      therapy used before admission to the PICU was cefotaxime associated with
      vancomycin (41 %), followed by cefotaxime alone (16 %). Positive cultures for
      Streptococcus pneumoniae were found in 11 patients (35 %). Pleural loculation was
      found in 14 patients (45 %). Treatment with intrapleural urokinase was used in 23
      patients (74 %). The mean chest tube drainage was 140 ml (SD: 175) in the 24
      hours before urokinase instillation and was 406 ml (SD: 289) in the 48 hours
      after fibrinolytic therapy (p < 0.05). Twenty-one patients (91 %) who received
      urokinase treatment had a good response. There were no complications during the
      treatment. The mean length of stay in the PICU was 5.8 days (SD: 2.6).
      CONCLUSIONS: The incidence of complicated pleural effusions due to S. pneumoniae
      has increased in the last few years, despite antibiotic therapy. Intrapleural
      urokinase is an effective treatment, including in empyemas without loculation.
      None of our patients required thoracotomy and there were few adverse effects.

PMID- 15871825
TI  - [Variations in serum ferritin and erythrocyte index in the first eight weeks of
      life in term newborn infants].
AB  - OBJECTIVE: To describe changes in erythrocyte index during the first 8 weeks of
      life in neonates in relation to their iron store. MATERIAL AND METHODS: We
      performed a longitudinal study of a group of healthy term newborn infants, in
      whom we evaluated erythrocyte index and serum ferritin (SF) values at birth and
      at weeks 4 and 8 of age. Depending on the comparison made in SF values between
      birth and 2 months, the infants were divided into two groups: group I (without
      variation in SF) and group II (with a decrease in SF). RESULTS: A total of 110
      neonates were included, with 46 neonates in group I and 64 in group II. No
      differences in demographic or hematologic data were found, including neonates
      with anemia or a decrease in hemoglobin values (5.2 vs. 5.5 g/dL). SF decreased
      to lower values in group II than in group I (215 vs. 194 microg/L, p < 0.001),
      with a greater number of neonates with low iron stores at 2 months of age (0.15
      vs. 0.37, p < 0.01; RR 2.464, 95 % CI: 1.162-5.227). CONCLUSIONS: In healthy term
      newborn infants, erythrocyte index at birth showed no relation with iron store.
      SF values at 2 months of age depended on SF concentrations at birth. Decreased
      hemoglobin and SF values are part of physiological adaptation in the first few
      months of life.

PMID- 15871826
TI  - [Study of bone mass in Turner syndrome].
AB  - OBJECTIVES: To evaluate bone mass in patients with Turner syndrome by measuring
      metacarpal cortical thickness and bone diameter before and after treatment with
      oxandrolone, growth hormone (GH) and estrogens. PATIENTS AND METHODS: We studied
      42 girls with Turner syndrome divided into the following groups: group I: 31
      patients aged between 3 and 15 years who were not treated before the study; group
      II: 15 patients treated with GH at start ages of between 5.2-14.8 years; group
      III: 17 patients treated with oxandrolone at start ages of between 5.3 and 15.2
      years; group IV: 17 patients treated with estrogens and divided in different
      subgroups: IVa: seven patients treated with GH and estrogens at start ages of
      between 6.1 and 12.9 years; IVb: five patients treated with oxandrolone and
      estrogens at start ages of between 13.4 and 17.4 years, and IVc: five patients
      treated with oxandrolone, GH and estrogens at start ages of between 10.3 and 16.1
      years. Bone mass was evaluated by a radiogrammetric method that measures the
      cortical thickness and bone diameter of three metacarpal bones with a magnifying
      glass. The results are expressed in SD according to Spanish longitudinal
      reference standards (Andrea Prader Center of Growth and Development) from 0.5 to
      9 years of age and to Swiss standards from the age of 10 years onwards.
      Statistical significance was set at p < 0.05. RESULTS: Group I (spontaneous
      development): cortical development was below the mean and was significantly
      diminished at the ages of 9, 13 and 14 years; bone diameter was decreased in
      relation to controls throughout the study period; group II (impact of GH
      treatment): cortical thickness showed a nonsignificant increase of 0.6 SD from
      baseline to years 3-4 of treatment and diameter increased by 0.5 SD from baseline
      to year 4 of treatment; group III (impact of oxandrolone): cortical thickness
      increased from -0.8 SD before treatment to 0.0 SD at years 2 and 3 of treatment;
      bone diameter increased from -1.5 SD at baseline to -1 SD at 3 years of
      treatment; group IV (impact of treatment with estrogens); IVa: cortical thickness
      and bone diameter increased; IVb: cortical thickness increased but bone diameter
      was unchanged; IVc: both cortical thickness and bone diameter increased.
      CONCLUSIONS: The results of this study show that cortical thickness and bone
      diameter are decreased in untreated girls with Turner syndrome; cortical
      thickness was significantly decreased at the ages of 9, 13 and 14 years, while
      bone diameter was diminished at all ages, suggesting the presence of osteopenia
      in these patients. GH treatment produced a nonsignificant increase in cortical
      thickness and bone diameter. Oxandrolone treatment showed a positive effect on
      bone mass during the first few years of therapy. Because of the small number of
      patients, conclusions cannot be reached on the effectiveness of estrogens.

PMID- 15871827
TI  - [The pediatrician and child death: integration of palliative care in the
      pediatric intensive care unit].
AB  - Palliative care is essential in the pediatric intensive care unit (PICU). Because
      of the mortality rates and the presence of life-threatening conditions in
      children admitted to the PICU, pediatricians must be prepared to provide
      palliative care independently of cure-directed therapies. The present article
      reviews certain issues, including the decision-making process in the PICU,
      psychosocial needs and susceptibility to burnout among PICU staff, and the
      emotions and attitudes of the staff when a child dies. We provide some guidelines
      on how to act when a child dies, how to meet with parents after the child's death
      and how to follow-up parental bereavement. Strategies that can help PICU
      pediatricians to cope with the numerous loses they experience are suggested.

PMID- 15871828
TI  - [Pediatric infections caused by nontuberculous mycobacteria].
AB  - During the last few years, nontuberculous mycobacteria (NTM) have been isolated
      with increasing frequency in our environment. However, there are only a few
      reports of pediatric NTM infections in Spain (13 articles since 1990). This
      article presents an update of the epidemiology, diagnostic methods, and treatment
      of these infections in children. The most frequent clinical syndromes caused by
      NTM include lymphadenitis, pulmonary and disseminated infections in
      immunocompromised children. NTM cervical adenitis usually causes chronic
      infection associated with sinus tract formation and scarring. The treatment of
      choice is surgical excision of the involved node. Incision and drainage of the
      enlarged node should be avoided because it can lead to chronic drainage or sinus
      tract formation. Medical treatment with azithromycin or clarithromycin associated
      with rifabutin, ethambutol or ciprofloxacin should be reserved for cases in which
      the family refuses surgery, a recurrence occurs or complete excision is
      impossible. Pulmonary disease caused by NTM is relatively rare in immunocompetent
      children, but is increasingly reported in children with cystic fibrosis. In these
      patients, the clinical significance of the presence of NTM in the sputum is
      unclear. The persistence of positive cultures, especially if bacilloscopy is
      positive and the patient shows clinical evidence of pulmonary disease
      exacerbation, is an indication to start treatment. Disseminated infection caused
      by NTM can appear in patients with severe immunodepression, especially in HIV
      infected children with CD4 cell counts of less than 100 cells/mm3. Early
      antibiotic therapy with at least three drugs including a macrolide, and immune
      recovery with aggressive antiretroviral therapy are the keys to improving quality
      of life and survival in these patients.

PMID- 15871830
TI  - [Effectiveness of activated factor VII in postoperative bleeding after cardiac
      surgery with extracorporeal membrane oxygenation].
AB  - A 4-year-old girl suffered severe postoperative chest tube drainage bleeding
      after cardiac transplant surgery requiring extracorporeal membrane oxygenation.
      Transfusions of platelets and fresh frozen plasma failed to decrease the
      bleeding. At 2.5 hours a dose of 180 mcg/kg of recombinant activated Factor VII
      was administered. The hemorrhage decreased from 45 ml/kg/h in the first 2.5 hours
      to 17 ml/kg/h in the next 2.5 hours. The same dose of recombinant activated
      Factor VII was administered and the hemorrhage suddenly decreased to 1.5 ml/kg/h
      in the next 2.5 hours, with subsequent disappearance. No adverse events related
      to activated Factor VII were observed. Recombinant activated Factor VII may be
      useful in some cases of severe postoperative bleeding in children after cardiac
      surgery. Randomized controlled studies are needed to confirm its safety and
      efficacy, and to evaluate the most suitable dose.

PMID- 15871829
TI  - [Use of activated factor VII in severe acute hemorrhage].
AB  - Acute hemorrhage is a sometimes serious complication that may arise in patients
      admitted to the intensive care unit with coagulopathy. The usual therapy is
      transfusion of blood components: fresh frozen plasma, platelets, fibrinogen, red
      cell concentrate and vitamin K. Tolerance or response can sometimes be poor. We
      present three patients aged 18 months, 4.5 and 10 years who suffered an acute
      episode of severe, life-threatening hemorrhage in the course of meningococcal
      sepsis (gastric hemorrhage), myelomonocytic leukemia (during splenectomy) and in
      the postoperative period after cardiovascular surgery. Traditional therapy was
      ineffective and activated factor VII was administered at doses of 50-70
      microg/kg, with rapid control of bleeding.

PMID- 15871831
TI  - [Neuropsychiatric disorders associated with streptococci: a case report].
AB  - Compulsive neuropsychiatric disorders are common in children and the most
      frequent is Gilles de la Tourette syndrome. Recently, a new disease has been
      described: the PANDAS syndrome (pediatric autoimmune neuropsychiatric disorders
      associated with streptococci). The etiology of this syndrome is uncertain but it
      has been associated with recent group A streptococcal infection (GAS). After an
      episode of pharyngitis, a boy aged 3 years and 9 months showed abrupt onset of a
      variety of neurobehavioral problems such as tics (consisting of elevation of the
      head and ipsilateral shoulder, winking, and grimaces) and compulsions (such as
      repeatedly hitting objects). A complete biochemical study was performed,
      including Cu and ceruloplasmin (which had normal values), antistreptolysin O
      (ASLO) and anti-DNAse (showing elevated values). Pharyngeal culture revealed GAS.
      The child was initially treated with valproic acid, but his subsequent
      improvement coincided with penicillin treatment for 10 days. Three months
      afterwards, ASLO values were reduced and at the 6-month follow-up the improvement
      was maintained even after suspension of valproic acid. Immunohistochemical
      studies were requested. PANDAS syndrome was first described in 1998 in a group of
      children who presented 1) obsessive compulsive disorders and/or tics, 2) episodic
      course with abrupt exacerbations, 3) abnormal results of neurologic examination
      (choreiform movements), and 4) temporal relation between GAS infection and onset
      of symptoms. The etiology of this syndrome is unclear, and it has been postulated
      that certain streptococcal antigens trigger antibodies which, through a process
      of molecular mimicry, cross-react with epitopes on the basal ganglia of
      susceptible hosts, such as the B8/17 antigen, among others. Current
      recommendations include penicillin treatment of each exacerbation with positive
      throat culture, and more aggressive therapies (intravenous immunoglobulin or
      plasmapheresis) when symptoms are severe. We believe that the case presented
      herein is a probable PANDAS syndrome, which would be the first case described in
      Spain.

PMID- 15871832
TI  - [Vascular liver tumors].

PMID- 15871833
TI  - [Palliative care].

PMID- 15871834
TI  - [Renal venous thrombosis in a neonate carrying the G20210A mutation of the
      prothrombin gene].

PMID- 15871835
TI  - [Sudden bilateral deafness after measles, mumps and rubella vaccination].

PMID- 15871836
TI  - [Group A beta-hemolytic Streptococcus as a cause of perianal dermatitis, fissures
      and balanoposthitis].

PMID- 15871837
TI  - [Analgesia and asepsis in ophthalmological examination of premature neonates].

PMID- 15871838
TI  - [Tetralogy of Fallot with absence of the left pulmonary branch. Surgical
      correction].

PMID- 15871839
TI  - [Testicular implants in children and adolescents].

PMID- 15871840
TI  - [An unusual foreign body].

PMID- 15871841
TI  - [Nocturnal episode of vomiting and tonic deviation of the eyes].

PMID- 15871843
TI  - A letter from the editor.

PMID- 15871844
TI  - Lipid lowering drugs and polyunsaturated fatty acids.

PMID- 15871845
TI  - Acute nateglinide administration in subjects with type 2 diabetes: effects on
      postprandial metabolism, coagulation, and fibrinolysis.
AB  - BACKGROUND AND AIM: Postprandial glycaemia and lipaemia are known risk factors
      for atherosclerosis in type 2 diabetes. Coagulation activation in the
      postprandial state also contributes to acceleration of atherosclerosis.
      Nateglinide is effective in reducing postprandial glycaemia. Its effect on
      glycaemia may also be beneficial in postprandial lipaemia and coagulation. The
      aim of this study was to examine the potential effect of a single dose of
      nateglinide on postprandial triglyceridaemia, coagulation, and fibrinolysis in
      patients with type 2 diabetes. METHODS AND RESULTS: Ten subjects with type 2
      diabetes, treated with diet alone were recruited in a crossover randomized study.
      In the morning, after a 12- to 14-h fast, each subject received a standard mixed
      meal (total energy 783 kcal), preceded by one tablet of 120 mg nateglinide or
      placebo. Venous blood samples were drawn prior to meal consumption and 6h
      afterwards for the measurement of plasma glucose, insulin, and C-peptide, lipids,
      coagulation, and fibrinolysis factors. As expected, there was a significant
      reduction in postprandial glycaemia after nateglinide administration compared to
      placebo (P<0.001). Plasma insulin levels were significantly higher after
      nateglinide than after placebo (P=0.002). Nateglinide administration resulted in
      a lower overall postprandial reduction of tissue-plasminogen activator than
      placebo (-2.9+/-1.3 vs. -8.3+/-3.7 ng/ml h, P=0.003). In addition, a significant
      reduction of postprandial plasminogen activator inhibitor-1 was observed in
      comparison with the baseline values after nateglinide (P=0.001), although the
      overall response was not significantly different after nateglinide and placebo
      (P=0.31). Plasma concentrations of C-peptide, lipids and the remaining
      coagulation parameters studied were not different between nateglinide and
      placebo. CONCLUSIONS: Acute nateglinide administration improves postprandial
      glycaemia and fibrinolytic activity in patients with type 2 diabetes. This
      combined effect, if confirmed by a long-treatment study, might reduce
      cardiovascular risk in type 2 diabetes.

PMID- 15871846
TI  - Effect of unsaturated fat intake from Mediterranean diet on rat liver mRNA
      expression profile: selective modulation of genes involved in lipid metabolism.
AB  - BACKGROUND AND AIM: The lipid content of Mediterranean diet is mostly accounted
      for its disease preventive action. We investigated whether the short term
      nutritional effect of a fat quota mainly derived from olive and fish oil affects
      liver mRNA expression profile in rats. METHODS AND RESULTS: The study was carried
      out using DNA microarray techniques. The effect was evaluated at liver mRNA
      expression level to identify genes whose expression was regulated by dietary
      modifications. Two groups of six rats were alternatively supplied for two weeks
      with either a control or with an experimental diet. Both diets were semisynthetic
      and isocaloric, with identical major nutrients composition (protein 20%,
      carbohydrates 56% and lipids 22% of total energy) being different only in the
      quality of fats. The lipid quota of the control diet contained exclusively
      saturated animal fats, derived from butter, while in the experimental diet some
      unsaturated fats were present, being derived also from olive and fish oil (10%
      and 6% of total energy, respectively). Out of 26,334 genes analyzed, 11,292 were
      found expressed in the liver, 72 were induced and 180 were inhibited from the
      experimental diet. Out of these, 33 of the induced and 59 of the inhibited
      species have a well known function. CONCLUSIONS: The diet with olive and fish oil
      modulates several genes related to lipolysis or lipogenesis and newly identified
      responders from other metabolisms. Some of these genes are also reported to be
      similarly modulated by the action of fibrates, but without the complete gene
      activation typical of these PPARalpha ligands.

PMID- 15871847
TI  - Effects of sibutramine-induced weight loss on cardiovascular system in obese
      subjects.
AB  - BACKGROUND AND AIM: To assess efficacy of sibutramine in obese subjects, and
      influence on hemodynamics, valve function and left ventricular (LV) geometry and
      performance. METHODS AND RESULTS: Three-month double-blind, parallel groups,
      randomized, placebo-controlled of 15 mg o.i.d. sibutramine administration
      combined with diet. Twenty-five to 65 year-old males or postmenopausal females,
      were enrolled if their BMI was between 30 and 40 kg/m(2), without evidence of
      concomitant diseases. Body weight, BMI, blood pressure (BP), echocardiographic LV
      mass, cardiac output, and diastolic function were measured. Body weight and BMI
      were better reduced with sibutramine (weight loss of 5% or more in 9 of 11
      patients) than placebo group (weight loss of 5% or more in 5 of 9 patients; all
      p<0.05). Systolic and diastolic BP decreased similarly in both arms. No
      difference in mean heart rate was detected between treatments. The two groups had
      slightly different LV geometry at baseline. LV mass decreased with weight loss,
      more in the sibutramine group (p<0.05), due to reduction in LV chamber size.
      Stroke volume tended to be reduced in the sibutramine group, influencing
      diastolic pattern. E/A ratio tended to decrease in the sibutramine group without
      changes in isovolumic relaxation time and deceleration time of E velocity. No
      onset or increased severity of valve regurgitation was detected. CONCLUSIONS:
      Combined to hypocaloric diet, sibutramine increases weight loss in obese
      individuals. Weight changes have positive effect on reduction of BP and
      contribute to reduce LV mass, the hallmark of markers of preclinical
      cardiovascular disease and most powerful predictor of adverse outcome.

PMID- 15871848
TI  - Investigation into the role of the hormone sensitive lipase -60C>G promoter
      variant in morbid obesity.
AB  - BACKGROUND: Hormone sensitive lipase (HSL) plays a central role in free fatty
      acid homeostasis in adipose tissue and in pancreatic beta-cells, where it
      contributes to the control of insulin secretion by generating long-chain fatty
      acids. AIM: We examined the frequency and association of the functional HSL
      promoter variant, -60C>G, in a German cohort of morbidly obese women (N=239) and
      men (N=55) and compared the frequency to a cohort of 199 blood donors, recruited
      from the same region. RESULTS: The rare allele frequency of -60C>G, in the obese
      individuals was significantly lower 0.031 (95% CI 0.02, 0.04), than that in the
      blood donors 0.061 (95% CI 0.04, 0.08) p=0.05. The association of the HSL -60C>G
      with lipid and glucose parameters was examined in the obese women (there were too
      few men for comparative analysis). In the obese women, those heterozygous for the
      -60G had significantly higher glucose levels compared to CC women, 142.71 (+/
      16.23) mg/dl vs. 110.34 (+/-1.79) mg/dl, respectively (p=0.0001). There was no
      statistically significant difference in other parameters. CONCLUSION: This study
      confirms a role for HSL in glucose homeostasis and the reduced frequency of the
      low expressing -60G promoter variant in obese individuals, together with existing
      published data, suggests that this allele might be protective against obesity.

PMID- 15871849
TI  - Lipid-lowering drugs and essential omega-6 and omega-3 fatty acids in patients
      with coronary heart disease.
AB  - BACKGROUND AND AIM: There are only little data about the effects of lipid
      lowering drugs (LLDs) on the metabolism of essential n-6 and n-3 fatty acids in
      patients with established coronary heart disease (CHD). METHODS AND RESULTS: Male
      patients with CHD and high cholesterol levels (>6.2 mmol/L) were randomized
      (double-blind protocol) to receive either simvastatin 20mg (S) or fenofibrate
      200mg daily (F) for 3 months. Dietary habits and plasma fatty acids were not
      different in the two groups at baseline. After treatment, there were significant
      changes in both the groups for the main n-6 fatty acids, with an increase in
      arachidonate (from 6.5+/-1.7% of total fatty acids to 7.5+/-2.1, p<0.001 in S and
      from 6.2+/-1.4 to 6.8+/-1.4, p<0.005 in F) and a decrease in linoleate (from
      26.9+/-3.9 to 24.2+/-3.6, p<0.001, and from 27.8+/-3.4 to 26.1+/-4.2, p<0.05, in
      S and F, respectively). In addition, there was a decrease in two major n-3 fatty
      acids (alpha-linolenate and docosahexanoate, both p<0.05), but only in F.
      CONCLUSIONS: For the first time in a double-blind randomized study in CHD
      patients, we report that LLDs significantly alter the metabolism of essential
      fatty acids that are critically important for the pathogenesis and prevention of
      CHD. Further studies are urgently needed to examine the effects of higher dosages
      of statins (as currently proposed to reduce more cholesterol) on these essential
      fatty acids in the clinical setting and the crucial questions of whether specific
      dietary intervention (combining low intake of n-6 fatty acids and high intake of
      n-3 fatty acids) may improve the effectiveness of these drugs.

PMID- 15871850
TI  - Use of antiplatelet therapy in a diabetic outpatient service of a large urban
      public hospital.
AB  - BACKGROUND AND AIM: Cardiovascular disease is the most important cause of
      mortality in type 2 diabetes. Aspirin treatment is effective in diabetic patients
      with cardiovascular disease and it does not significantly increase the risk of
      retinal haemorrhage, gastrointestinal bleeding or hemorrhagic stroke. The
      American Diabetes Association (ADA) recommends the use of aspirin in all adult
      patients with diabetes and macrovascular disease, and suggests to start treatment
      with aspirin for primary prevention in diabetic patients >or=40 years of age and
      with one or more other cardiovascular risk factors in the absence of specific
      contraindications. METHODS: In this observational retrospective study, we have
      selected from our database (17,732 clinical reports) all the type 2 diabetic
      patients 41--80 years of age, who had at least one visit to our outpatient
      service in the following two periods: A (from 1 July 1995 to 30 June 1996) and B
      (from 1 July 2002 to 30 June 2003), then analysed the patient-records for
      prescription of antiplatelet agents. RESULTS: Our analysis has shown that
      antiplatelet agents were prescribed to 15% of the type 2 diabetic patients in
      period A (10.8% and 53.4% -- primary and secondary prevention, respectively) and
      to 22.8% of the patients in period B (19.1% and 60.5% -- primary and secondary
      prevention, respectively). CONCLUSIONS: Patients with type 2 diabetes and high
      cardiovascular risk are not always under antiplatelet treatment despite the ADA
      recommendations, particularly for primary prevention. However, our data show an
      increased trend in prescriptions from 1997, when the first ADA specific
      guidelines for aspirin therapy were published.

PMID- 15871851
TI  - Effect of statins on LDL particle size in patients with familial combined
      hyperlipidemia: a comparison between atorvastatin and pravastatin.
AB  - BACKGROUND AND AIM: Elevation of plasma cholesterol and/or triglycerides, and the
      prevalence of small dense low density lipoproteins (LDL) particles remarkably
      increase the risk in patients with familial combined hyperlipidemia (FCHL). There
      are, at present, inconsistent data on the effects of different treatments on size
      and density of LDL particles in FCHL patients. METHODS AND RESULTS: A
      multicenter, randomized, double-blind, double-dummy, parallel group study was
      designed to evaluate the effect of 3 months' treatment with atorvastatin
      (10mg/day) or pravastatin (20mg/day) on the lipid/lipoprotein profile and LDL
      size in a total of 86 FCHL patients. Both statins significantly lowered plasma
      total and LDL cholesterol, with a significantly higher hypocholesterolemic effect
      observed with atorvastatin (-26.8+/-11.1% and -35.9+/-11.1%, respectively)
      compared to pravastatin (-17.6+/-11.1% and -24.5+/-10.2%). The percent decrease
      in plasma triglycerides was highly variable, but more pronounced with
      atorvastatin (-19.8+/-29.2%) than with pravastatin (-5.3+/-48.6%). Opposite
      changes in LDL size were seen with the 2 treatments, with increased mean LDL
      particle diameter with atorvastatin, and decreased diameter with pravastatin, and
      significant between treatment difference in terms of percent modification vs
      baseline (+0.5+/-1.6% with atorvastatin vs -0.3+/-1.8% with pravastatin).
      CONCLUSIONS: The present results support the evidence indicative of a greater
      hypocholesterolemic effect of atorvastatin compared to pravastatin, and in
      addition show a raising effect of atorvastatin on the size of LDL particles in
      FCHL patients.

PMID- 15871852
TI  - Structural and functional abnormality of systemic microvessels in cardiac
      syndrome X.
AB  - BACKGROUND AND AIM: Microvascular damage of coronary bed has been considered the
      main pathogenetic factor of cardiac syndrome X (chest pain, exercise-induced
      ischemic ST-segment changes and angiographically normal coronary arteries).
      Previous studies have demonstrated that vascular abnormalities are not confined
      to the heart, suggesting a peripheral vascular dysfunction. On the hypothesis of
      a generalized microvascular disturbance in cardiac syndrome X, we performed a
      morphologic and functional study of systemic microcirculation in patients with
      syndrome X compared to normal subjects. METHODS AND RESULTS: Microvessels were
      evaluated with intravital videocapillaroscopy (VCP) executed in peripheral and
      conjunctival observation sites which explore micro and paramicrocirculation;
      biohumoral study included markers of inflammation and of endothelial function,
      coagulative-fibrinolytic system and lipid metabolism. Videocapillaroscopy showed
      several morphologic changes (present in high percent of patients with syndrome X
      and not in controls) and significant quantitative alterations (capillary density,
      granular flow score, alterations of vessel profile, length of capillary loop
      branches and of arteriole/venule diameter) which indicated a severe alteration of
      whole vessel structure and an important rearrangement of microvascular
      disposition. In a similar way, the humoral study showed some significant changes
      of endothelial (vWF, ICAM-1, E-sel, PAI-1), inflammatory (C-reactive protein
      (CRP), fibrinogen) and metabolic factors (HDL-chol) which are commonly associated
      with inflammatory response. CONCLUSIONS: We conclude that patients with cardiac
      syndrome X exhibited some structural and functional alterations of systemic
      microvasculature; the pattern is similar to that detected in systemic
      inflammatory diseases and suggests a vascular lesion of inflammatory type. The
      same changes could be operating also in coronary microvessels of patients with
      syndrome X.

PMID- 15871853
TI  - Circulating soluble E-selectin levels and the Ser 128Arg polymorphism in
      individuals from different ethnic groups.
AB  - BACKGROUND AND AIM: An association between the Ser128 Arg polymorphism and
      coronary heart disease (CHD) has been previously demonstrated in a white
      population. The aim of this study was to investigate whether the Ser128 Arg
      polymorphism of the E-selectin gene is associated with soluble E-selectin levels
      in individuals from a multiethnic population. METHODS AND RESULTS: Plasma sE
      selectin levels and the Ser128 Arg E-selectin gene polymorphism were determined
      in 244 white (109 females), 176 of African origin (90 females) and 208 South
      Asian (95 females) healthy individuals living in England selected from the
      Wandsworth Heart and Stroke Study (WHSS). The substitution of serine for arginine
      (A to C mutation) was more common in whites (9.6%) and South Asians (7.9%)
      compared to the people of African origin (3.7%); p=0.005. The C mutation had no
      effect on sE-selectin levels in any ethnic group. CONCLUSIONS: We found a lower
      frequency of this polymorphism in the people of African origin who have a low CHD
      risk. However, in this study the polymorphism was not associated with circulating
      sE-selectin levels. Whether it plays a role in determining ethnic differences in
      vascular disease via a mechanism affecting leukocyte recruitment remains to be
      determined.

PMID- 15871854
TI  - Wide pulse pressure is an independent predictor of cardiovascular mortality in
      Puerto Rican men.
AB  - BACKGROUND AND AIM: Emerging evidence suggests that pulse pressure is an
      independent predictor of risk for cardiovascular mortality. New studies in
      diverse populations are needed to further establish the applicability of this
      finding. Thus, the purpose of this study is to examine the relationship between
      pulse pressure and cardiovascular mortality in a cohort of Puerto Rican men after
      12 years of follow-up. METHODS AND RESULTS: The Puerto Rico Heart Health Program
      is a study of coronary disease risk factors in men aged 35-79 years at baseline
      who had an initial examination during the years 1962-1965. It was attended by
      9824 subjects representing 80% of the total age-specific male residents in 4
      rural and 3 urban areas of Puerto Rico. Cardiovascular risk factors including
      systolic and diastolic blood pressures were monitored prospectively. This study
      includes 9106 men free of overt CHD at baseline who were stratified by quartiles
      of pulse pressure in mmHg: quartile 1, <or=38, quartile 2, 39-46; quartile 3, 47
      56; and quartile 4, >or=57. The odds ratio of cardiovascular mortality was
      calculated using logistic regression analysis. After adjusting for age,
      education, smoking status, hypercholesterolemic status, physical activity,
      diabetic status and mean arterial pressure, we found that those in the highest
      quartile of pulse pressure (pulse pressure>=57) had significantly higher
      cardiovascular mortality than those in the lowest quartile (reference group)
      (OR=1.38 95% CI=1.01-1.88). CONCLUSION: Our findings showed that a wide pulse
      pressure is independently associated with cardiovascular mortality in this group
      of Puerto Rican men.

PMID- 15871855
TI  - Definition of high risk individuals to optimise strategies for primary prevention
      of cardiovascular diseases.
AB  - The identification of high risk individuals is one of the main goals of
      cardiovascular primary prevention and constitutes the basis for implementing
      actions oriented toward reducing modifiable risk factors at individual level,
      from changing life styles to drug interventions. The most appropriate method for
      identifying high risk individuals is the evaluation of their absolute global
      risk, a probability indicator of incidence, predictable on the basis of risk
      factor levels. Risk functions, derived from longitudinal studies, are used to
      identify persons at high probability to develop cardiovascular diseases. The
      appropriateness of the use of these risk functions depends upon the
      characteristics of the population that generated them and of individuals which
      they are applied to. Risk charts are simply absolute global risks calculated by
      classes of risk factors; risk scores are more precise evaluation derived from
      absolute global risks calculated by continuous levels of risk factors. Risk
      charts and scores are formed through the risk functions derived from different
      studies: Framingham, PROCAM (Munster), Seven Countries Study, SCORE and Progetto
      CUORE. A further chart has been created using the Framingham Study and adapted to
      the guidelines of New Zealand regarding the treatment of dyslipidemias and blood
      pressure. Major differences can be found in the availability of risk factors in
      men and women and in the use of fatal and non-fatal coronary and cerebrovascular
      events as end-points. All these studies use different diagnostic criteria for
      identification, classification and validation of events. The awareness of the
      risk charts differences is a key issue to refine tools for prevention of
      cardiovascular disease in populations with different probabilities of disease
      frequency.

PMID- 15871856
TI  - Health implications of homocysteine and folates: possible preventive measures.

PMID- 15871857
TI  - Correlation between dietary polyunsaturated fatty acids and plasma homocysteine
      concentration in vitamin B6-deficient rats.
AB  - BACKGROUND AND AIM: Vitamin B6 as cofactor of Delta6 desaturase is involved in
      polyunsaturated fatty acid metabolism; moreover, it is a cofactor of the trans
      sulfuration pathway of homocysteine. Some studies report that low concentrations
      of pyridoxine, by increasing homocysteine levels, are associated with coronary
      artery disease, and carotid and arterial lesions. The aim of this study was to
      verify whether different dietary amounts of polyunsaturated fatty acids
      associated with low content of vitamin B6 could modulate homocysteinemia. METHODS
      AND RESULTS: Thirty-two rats were divided into two groups, one fed a diet with
      adequate vitamin B6 content the other a diet containing low amount of the same
      vitamin. Within each group, rats were divided into two subgroups differing in the
      polyunsaturated fatty acid content of the diet (63 and 33%, respectively). The
      vitamin B6-deficient diet induced an increase in homocysteine concentration
      compared to the vitamin B6-normal diet. This increase was tenfold in the subgroup
      fed high polyunsaturated fatty acid levels and twofold in the other subgroup. The
      fatty acid composition of liver phospholipids showed a lower arachidonic acid
      relative molar content and a lower 20:4/18:2 ratio in vitamin B6-deficient groups
      compared with B6-normal groups. CONCLUSIONS: On the basis of the different
      biological functions of pyridoxine and considering that some factors closely
      related to atherosclerosis are vitamin B(6) dependent, adequate pyridoxine
      availability could be necessary to assure a normal long chain fatty acid
      metabolism and to reduce the risk linked to hyperhomocysteinemia.

PMID- 15871858
TI  - Role of vitamins B6, B12 and folic acid on hyperhomocysteinemia in a Pakistani
      population of patients with acute myocardial infarction.
AB  - BACKGROUND AND AIM: Pakistani people belong to an ethnic group which has the
      highest rate of coronary artery disease (CAD). We investigated the possible
      correlation between deficiency of vitamins B6, B12 or folic acid and
      hyperhomocysteinemia in Pakistani patients with acute myocardial infarction
      (AMI). A case-control study was carried out involving 224 AMI patients (age 30-70
      years; 55 females and 169 males) and 126 normal healthy subjects (age 31-70
      years; 35 females and 91 males). METHODS AND RESULTS: Fasting venous blood was
      obtained from cases and controls. Serum was analyzed for folic acid and B12 using
      radioassays. Plasma was analyzed for pyridoxal phosphate (PLP; coenzymic form of
      B6) using a radioenzymatic assay and for total homocysteine using a fluorescence
      polarization immunoassay. Mean serum B12 concentration in AMI patients was found
      to be significantly lower than the mean for controls (241+/-185 pg/ml vs 608+/
      341 pg/ml; p < 0.001). Mean serum folate level in patients was also found to be
      lower than controls (3.35+/-3.78 ng/ml vs 4.93+/-2.93 ng/ml), however, the
      differences were not statistically significant. Similarly, mean PLP concentration
      in plasma of cases (19.4+/-24.4 nmol/l) was lower than the concentration in
      controls (23.2+/-17.6 nmol/l), but the difference was not statistically
      significant. Mean plasma homocysteine level in AMI cases (18+/-8.36 micromol/l)
      was higher than the mean level in controls (16.4+/-4.9 micromol/l), but not to a
      significant extent. However, this mean homocysteine concentration in normal
      healthy subjects was among the highest reported in the literature and was
      significantly more than mean values reported in most Eastern and Western studies.
      Compared to controls, there was significantly greater deficiency of folate (32.5%
      vs 67.1%), B12 (3.2% vs 63.4%) and PLP (49.2% vs 74.1%) in AMI patients.
      Deficiencies of folate, B12 and PLP were defined as serum folate levels less than
      3.5 ng/ml, serum levels of B12 less than 200 pg/ml and plasma PLP levels less
      than 20 nmol/l. Mean plasma homocysteine levels in smokers were found to be
      significantly higher in both cases and controls. Similarly, mean serum folate
      levels in smokers (compared to nonsmokers) were significantly lower in both cases
      and controls. CONCLUSIONS: Substantial nutritional deficiencies of these three
      vitamins along with mild hyperhomocysteinemia, perhaps through an interplay with
      the classical cardiovascular risk factors (highly prevalent in this population),
      could be further aggravating the risk of CAD in the Pakistani population.

PMID- 15871859
TI  - Plasma homocysteine levels in patients with type 2 diabetes in a Mediterranean
      population: relation with nutritional and other factors.
AB  - BACKGROUND AND AIM: Hyperhomocysteinemia is a major and independent risk factor
      for atherothrombotic vascular disease. It may be promoted by genetic factors,
      nutritional deficiencies of the vitamin cofactors required for homocysteine
      metabolism, and other modifiable factors. This cross-sectional study investigated
      the effect of dietary habits and lifestyle on plasma total homocysteine (tHcy)
      levels in patients with type 2 diabetes in a Mediterranean population. METHODS
      AND RESULTS: A total of 126 diabetic and 76 healthy subjects were interviewed
      using a food-frequency questionnaire. Information consisted of dietary and
      smoking habits, coffee and alcohol consumption and physical activity recording,
      during the month prior to enrollment. Measurements included blood pressure, body
      mass index (BMI), waist-to-hip ratio (WHR), plasma tHcy, folate, vitamin B12,
      lipids, HbA(1c), creatinine, uric acid, and glomerular filtration rate (GFR).
      Plasma tHcy levels were not different between diabetic and control subjects
      (11.49+/-3.68 vs 12.67+/-3.79 micromol/l respectively, P = 0.40). Diabetic
      subjects had significantly higher plasma folate levels and consumed more fish,
      fruit and vegetables, in comparison with controls. Controls consumed more red
      meat, coffee, and alcohol. Multivariate analysis in diabetic subjects, after
      controlling for age, sex, systolic blood pressure, duration of diabetes, GFR,
      plasma uric acid levels, and the amount of the weekly consumption of fruit and
      vegetables, demonstrated that age, GFR and the weekly amount of fruit and
      vegetable consumption were independently associated with plasma tHcy
      concentrations [regression coefficient (B) = 0.11, SE (B) = 0.03, P = 0.001, B = 
      0.07, SE (B) = 0.01, P < 0.0001, and B = -0.05, SE (B) = 0.02, P = 0.04,
      respectively]. The weekly amount of coffee, alcohol and red meat consumption, and
      physical activity level were not related with plasma tHcy levels in either study
      group. CONCLUSIONS: 1) Plasma tHcy levels were not different in the diabetic
      group as compared to the control group. 2) In patients with type 2 diabetes age,
      GFR and the consumption of fruit and vegetables were strong and independent
      determinants of plasma tHcy levels.

PMID- 15871860
TI  - Reduced serum homocysteine levels in type 2 diabetes.
AB  - OBJECTIVE: To assess the contribution of fasting blood glucose and methylene
      tetrahydrofolate reductase (MTHFR) gene polymorphism on fasting serum
      homocysteine (tHcy) levels in patients with uncomplicated type 2 diabetes
      compared with healthy subjects. METHODS AND RESULTS: We studied 105 type 2
      diabetic patients without cardiovascular complications or diabetic nephropathy
      (55 males, 50 females, mean age 53+/-10 years, mean duration of diabetes 11.4+/-8
      years) and 120 age- and sex-matched control subjects (65 males, 55 females, mean
      age 52+/-8 years). tHcy and other biochemical variables were measured. The C677T
      MTHFR gene polymorphism was determined by analysis of HinfI restriction fragment
      length polymorphism tHcy levels were significantly lower in diabetic patients
      compared with control subjects (7.7 +/- 2.2 vs. 11.8 +/- 4.5 micromol/l, P <
      0.0001). In both patients and control subjects, homocysteinemia was higher in men
      than in women (8.4+/-2.6 vs. 7.3+/-2.0 micromol/l, P < 0.03, and 13.0+/-5.3 vs.
      10.4+/-2.6 micromol/l, P < 0.0001, respectively). Levels were slightly higher in
      subjects with the mutated Val/Val genotype compared with the Ala/Val plus Ala/Ala
      genotypes in both diabetic patients (P < 0.02) and control subjects (P < 0.003).
      On simple regression analysis, tHcy was inversely related with blood glucose
      levels (P < 0.02) and directly with sex (P < 0.04) in diabetic patients, and with
      sex (P < 0.0001), age (P < 0.02), BMI (P < 0.03), systolic and diastolic blood
      pressure (P < 0.0004 and P < 0.0002), uric acid and creatinine (P < 0.0001 and P
      < 0.0003) in control subjects. On multiple regression, tHcy levels were
      associated with sex (P < 0.03) and glucose levels (P < 0.04) in diabetic
      patients, and with uric acid (P < 0.002) and MTHFR genotype (P < 0.03) in control
      subjects. CONCLUSION: In type 2 diabetic patients without nephropathy, basal
      levels of tHcy were 35% lower compared with healthy controls. Chronic
      hyperglycemia may control tHcy by affecting its renal excretion, or accelerate
      hepatic trans-sulfuration secondary to insulin disorders.

PMID- 15871861
TI  - Plasma homocysteine is related to folate intake but not training status.
AB  - BACKGROUND AND AIM: Lifestyle including intakes of several essential nutrients
      and physical activity are of particular interest in reducing plasma total
      homocysteine concentration (tHcy), a risk factor for cardiovascular diseases. The
      aim of this study was to determine in athletes, whether dietary factors such as
      intakes of folate, vitamin B6 and B12 were associated with lower plasma tHcy, and
      whether this depended on daily energy expenditure (EE) and type of physical
      activity performed (aerobic, anaerobic, intermittent). METHODS: Seventy-four well
      trained athletes completed 7-day food and activity records in a cross-sectional
      study. Blood was sampled on day 8. RESULTS: Percentage of vegetal protein,
      vitamin B6, and folate intakes were higher and tHcy was lower (1) in athletes
      with high EE (> 16.72 MJ/d) compared to athletes with lower EE; (2) in aerobic
      athletes compared to intermittent athletes and sedentary subjects. After backward
      step by step analysis, folate intake was the only significant variable retained
      in the model to explain tHcy variability. Moreover, after introducing folate
      intake as a covariate in ANOVA tests, group effects on tHcy were no longer
      significant. Nutrient density of folate was inversely correlated to tHcy in
      athletes (r = -0.33; P = 0.004). CONCLUSION: High energy intake (> 16.72 MJ/d)
      allows the necessary folate intake (> 500 microg/d) for tHcy decrease to occur,
      which is moreover favored by aerobic activity. The mechanism underlying low tHcy
      in relation to high EE could only play a minor role when compared to the effect
      of dietary folate intake on tHcy.

PMID- 15871862
TI  - Effects of marathon running on plasma total homocysteine concentrations.
AB  - AIMS: There is evidence of an excess of acute cardiovascular (CV) events in
      marathon runners. High plasma total homocysteine (tHcy) concentrations are a
      recognised risk factor for CV events. Therefore, we investigated the changes in
      plasma tHcy concentrations 24h before and after a marathon race. METHODS AND
      RESULTS: Twenty-two non-professional male athletes, mean age 35.6 (6.6), range 23
      49 years, were studied the day before and 24 h after finishing a marathon race.
      None of the athletes was a carrier of the MTHFR 677TT genotype and no ingestion
      of supplements of vitamins (B12, B6, folic acid) was allowed. RESULTS: Changes in
      plasma folate and plasma vitamin B12 concentrations were not detected post-race,
      but a significant increase in plasma tHcy concentrations was demonstrated. Plasma
      tHcy increased 19% 24h after the race. Before the race 20% of the subjects had a
      plasma tHcy concentration > 10 micromol/l (cut-off point for ischaemic heart
      disease risk), while after the race 50% had plasma tHcy concentrations> 10
      micromol/l. CONCLUSION: An increase in plasma tHcy concentrations was observed
      after a marathon race in non-professional not well-trained male athletes
      performing strong physical activity. The potential physiological or pathological
      implications of this finding are unknown.

PMID- 15871863
TI  - Is homocysteine important as risk factor for coronary heart disease?
AB  - AIM: Homocysteine (Hcy), a sulfur-containing amino acid product of methionine
      metabolism, may play an important role in the development of cardiovascular
      disease. In this paper we review available knowledge on the pathways leading to
      synthesis and degradation of Hcy, as well as on the genetic and environmental
      factors affecting its plasma levels, focussing on its potential role in the
      development of coronary heart disease. DATA SYNTHESIS: Hyperhomocysteinemia
      (HHcy) is determined by genetic and environmental factors and represents a
      modifiable cardiovascular risk factor since vitamin supplementation has been
      shown to effectively lower plasma homocysteine levels. While case-control and
      cross-sectional studies consistently showed an association of HHcy with
      cardiovascular disease, prospective studies have given conflicting results. Thus,
      the role of HHcy in the development of coronary heart disease is still under
      debate. Furthermore, it remains unclear which patients should be screened for
      HHcy and treated to correct HHcy. CONCLUSIONS: Available information collectively
      suggests that although HHcy can be regarded as a minor risk factor for coronary
      heart disease, it interacts with other risk factors in triggering new events in
      patients with known CAD. Thus, the treatment of mild HHcy with folate
      supplementation is appropriate in particular in high risk patients or patients
      with established CAD who do not present with the "traditional" risk factors.

PMID- 15871864
TI  - A standardized quality assessment system to evaluate pain detection and
      management in the nursing home.
AB  - CONTEXT: Assessment and management of pain for nursing home residents is
      frequently reported to be inadequate, yet few studies have used objective
      criteria to measure the quality of care related to pain. OBJECTIVE: Field test a
      standardized resident interview and medical record review protocol to assess and
      score quality indicators relevant to pain. DESIGN: Descriptive. SETTING: Thirty
      nursing homes (NHs). PARTICIPANTS: Seven hundred ninety-four residents met
      overall eligibility criteria. Quality indicators were scored for those residents
      who met specific eligibility requirements for each pain indicator. MEASUREMENTS:
      Medical record reviews were completed for 542 participants, and data were used to
      score 12 indicators related to pain assessment, management, and response to
      treatment. A seven-item pain interview was attempted with all 794 participants
      and completed with 478 participants who were rated by NH staff as cognitively
      aware. RESULTS: Quality indicators could be reliably scored. Physicians scored
      low on assessment of pain, performing targeted history and physical examinations,
      documenting risk factors for use of analgesics, and documenting response to
      treatment. Forty-eight percent of participants (227/478) reported symptoms of
      chronic pain during the interview, and 81% of this group reported a preference
      for a pain medication. However, nearly half had no physician assessment of pain
      in the past year and only 42% were receiving pain medication. Licensed nurse
      assessments of pain were documented weekly; but, more than 50% of those reporting
      symptoms of chronic pain on interview had nurse pain scores of 0 for 4
      consecutive weeks prior to interview. CONCLUSIONS: Infrequent or incomplete
      physician pain assessment and treatment and inaccurate documentation by licensed
      nurses limits evaluation of pain care quality based on medical record review
      alone. A brief resident interview identified participants reporting symptoms of
      chronic pain not documented in the medical record and those with a preference for
      medication. Initial targeting of residents with self-reported pain maximizes the
      efficiency of the standardized scoring system described in this study. Focusing
      on explicit process measures clearly identifies areas for improvement and
      represents an important step in assessing the quality of pain care in the NH.

PMID- 15871866
TI  - Predictors of do not resuscitate orders in the nursing home.
AB  - BACKGROUND: The outcome of cardiopulmonary resuscitation of residents of long
      term care facilities is poor. However, only about one half of residents of long
      term care facilities have a do not resuscitate (DNR) order. The remainder usually
      have resuscitation by order or by default policy. Understanding predictors of DNR
      may help clinicians address end-of-life issues with the older long-term care
      population. OBJECTIVES: To determine (1) the prevalence of DNR orders, and (2)
      predictors of DNR orders in older institutionalized individuals in a large
      community teaching nursing home. METHODS: A cross-sectional chart review study of
      177 consecutively located older patients from an 899-bed academic long-term care
      facility. RESULTS: The prevalence of a DNR order was 40%. The frequency of
      ordering DNR was greater in subjects who were 85 years or older compared with
      subjects who were younger than 85 years (57% vs. 30%, P < .05). Ordering DNR was
      associated significantly with race (49% of whites compared with 13% African
      Americans, P < .05) but not with sex. Subjects with a DNR order were more likely
      to have been diagnosed with depression (52% vs. 35%, P < .05) but not dementia,
      and overall had greater number of medical conditions (5.9 +/- 2 vs. 5.1 +/- 2, P
      < .05) compared with subjects without DNR orders. The frequency of DNR orders did
      not significantly differ between subjects who were able to ambulate (with or
      without assistance) compared with subjects who were wheelchair or bed bound.
      Using logistic regression analysis, only age (with a B of -1.04 and P of .017)
      and race (with a B of 1.4 and a P of .01) were independent predictors of DNR
      status. CONCLUSION: Fewer than half of this sample of long-term care residents
      had a DNR order. Among seven factors studied, only age and race were independent
      predictors of DNR status in the nursing home.

PMID- 15871865
TI  - Nursing home resident barriers to effective pain management: why nursing home
      residents may not seek pain medication.
AB  - OBJECTIVES: Multiple barriers to effective pain management are present in the
      nursing home setting. The purpose of this analysis was to determine the extent to
      which residents in pain declined to request pain medication from the staff, and
      the reasons provided by the residents to explain this behavior. DESIGN: Every 3
      months, a 20% sample of residents in 12 nursing homes was administered a short
      pain interview, then observed for pain indicators. Medical records were reviewed
      at the same time for documentation about pain and its treatment. All residents
      were asked if they had pain (or a similar word) now or in the past 24 hours. They
      were also asked if they had pain but did not request pain medication. If
      affirmative, the resident was asked to provide up to three reasons for not
      requesting medication. SETTING: The study was conducted in 12 Colorado nursing
      homes, located in both urban and rural settings. PARTICIPANTS: A total of 2033
      nursing home residents completed pain interviews and/or were observed for pain
      indicators by trained research assistants. These interviews took place before,
      during, and after implementation of an intervention to improve pain practices.
      MEASUREMENTS: A cognitive organizing structure was used to categorize resident
      responses into a coherent classification. Individual responses were assigned by
      team members to the appropriate category using a consensus process. The final
      classification scheme consisted of 10 categories of reasons why residents do not
      request pain medication. RESULTS: More than one-half of residents (59.5%)
      reporting pain in the past 24 hours did not request medication for that pain.
      Subjects in pain were most likely to state medication concerns or stoicism as the
      reasons for not requesting pain medication. Concerns about staff reactions to a
      request or perceptions that the staff was too busy were also mentioned frequently
      by the residents. Subgroup analyses suggested that residents in pain but not
      requesting pain medication were significantly more likely to be in rural rather
      than urban nursing homes (67.9% vs. 52.9%, P < or = .01), and white as compared
      to nonwhite ethnicity (60.6% vs. 52.1%, P < or = .05). They also tended to be
      older on average (80.4 +/- 12.1 years vs. 77.9 +/- 12.7 years, P < or = .01) than
      residents who did request pain medication. Finally, residents in pain but not
      requesting pain medication were significantly more likely to report having both
      continuous (c) and intermittent (i) pain (71.8% [c + i] vs. 61% [c] or 56.5% [i],
      P < or = 0.01). CONCLUSION: Interventions to reduce pain in nursing home
      residents need to be responsive to the concerns of the residents. It must be
      acknowledged that resident preferences and beliefs may lead to declined pain
      interventions regardless of the staff's motivation to make the resident more
      comfortable. Staff nurses also need to make a more concerted effort to
      systematically assess pain and offer pain medication to residents rather than
      rely on resident requests.

PMID- 15871867
TI  - Do not hospitalize orders in nursing homes: a pilot study.
AB  - OBJECTIVES: To determine (1) the point prevalence of do not hospitalize (DNH)
      policies in nursing facilities directed by members of the American Medical
      Directors Association (AMDA) Foundation Long-term Care Research Network, (2) the
      frequency with which physicians are writing DNH orders, and (3) respondent
      perceptions about the appropriateness of the number of DNH orders as too few or
      too many and reasons for such perceptions. DESIGN: Online survey of members of
      the AMDA Foundation Long-term Care Research Network. SETTING: Nursing facilities.
      PARTICIPANTS: All members of the AMDA Foundation Long-term Research Network on
      July 1, 2003 were eligible for participation (N = 293). INTERVENTION: None.
      MEASUREMENTS: Demographic information regarding census, region, setting,
      governance, presence of teaching and/or hospice affiliation, prevalence of DNH
      orders, and qualitative information regarding the use of DNH orders in each
      facility. RESULTS: The response rate was 32% (n = 95). DNH policies were in place
      for 62% of facilities and the prevalence of DNH orders ranged from 12% to 23%
      when facilities were stratified by size. Percentage of residents with documented
      DNH orders ranged from 0% to 99% at individual facilities. No significant
      differences were found although trends were noted as follows: chain facilities
      had fewer DNH policies (RR = 0.8; 95% CI = 0.6-1.1) whereas rural facilities (RR
      = 1.1, 95% CI = 0.8-1.5) and those associated with a teaching institution (RR =
      1.1, 95% CI = 0.8-1.5) were more likely to have a DNH policy. Of respondents, 80%
      indicated that physicians in their facilities were writing DNH orders but 77%
      believed that the number of DNH orders was too few. Respondents cited overly
      optimistic prognosis and lack of knowledge about DNH orders as barriers to
      writing more DNH orders. CONCLUSION: The prevalence of DNH orders in this
      investigation is higher than previous estimates from national data samples. Most
      facilities had a DNH policy and although respondents indicated that physicians do
      write DNH orders, they believed that DNH orders were not utilized frequently
      enough. There is a large variation in prevalence of DNH orders across the
      facilities included in this survey. Barriers to use, as perceived by medical
      directors, included unrealistic expectations by family, fear of litigation, and
      staff discomfort with managing residents who experience clinical decline.
      Nevertheless, DNH orders are used extensively in some facilities associated with
      members of the AMDA Foundation Long-term Care Research Network.

PMID- 15871869
TI  - Physician care in assisted living: a qualitative study.
AB  - OBJECTIVES: To identify patterns and emerging concepts used by assisted living
      (AL) residents, their families, and the facility staff to describe the care
      provided by physicians to the AL residents. DESIGN: Qualitative research and
      analysis based on audio-taped and transcribed ethnographic interviews with
      residents, family members, and staff of AL facilities. SETTING: Three AL
      facilities representing small and traditional AL facilities. PARTICIPANTS: Forty
      three in-depth interviews including 16 AL residents, 13 family members, three
      facility managers, and 11 staff members. MEASUREMENTS: Ethnographic, audio-taped
      interviews coded by consensus by a doctoral-level analysis team. Coding focused
      broadly on any references to physicians or doctors in the interviews. RESULTS:
      Emergent themes included four major physician-related themes in AL including:
      magnification of physician authority; disagreements with physician care;
      physician communication; and continuity/discontinuity of physician care.
      CONCLUSION: Physicians caring for residents of AL facilities should consider how
      residents, families, and staff stakeholders may influence their patient care for
      AL residents in terms of their authority, decision-making, communication, and
      continuity of care.

PMID- 15871868
TI  - Physician and nurse staffing in nursing homes: the role and limitations of the
      Online Survey Certification and Reporting (OSCAR) system.
AB  - OBJECTIVES: To assess nursing home staffing data reported in the Online Survey
      Certification and Reporting (OSCAR) system database for research and policy.
      DESIGN: Comparisons were made between OSCAR and a concurrent research survey of
      staffing data collected for the same facilities, using inter-rater agreement and
      correlation analyses. SETTING: Freestanding nursing homes from New York State
      (NYS) in 1997 (N = 327). MEASUREMENTS: Selected staffing variables were defined
      in comparable terms in both OSCAR and the NYS survey. RESULTS: The two data
      sources were in substantial agreement on the reported availability of a full-time
      physician (other than medical director) and of a physician assistant or nurse
      practitioner (Kappa >0.7), and they correlated well in the full-time equivalent
      (FTE) number of such staff (Spearman correlation >0.6). The correlation was 0.8
      for FTE registered nurses (RNs), 0.7 for licensed practical nurses (LPNs), and
      0.8 for certified nurse aides (CNAs). In terms of average nurse hours per patient
      day, separately for RNs, LPNs, CNAs, and all combined, the correlation was
      relatively weak (between 0.3 and 0.6). Overall staffing levels tended to be lower
      in OSCAR than in NYS. CONCLUSION: The OSCAR data are useful for exploring
      relationships between staffing and various quality of care outcomes, but may not
      be accurate enough on a case-specific basis, or to determine policy regarding
      minimal staffing levels using average nurse hours per patient day measures. More
      systematic and timely efforts are needed to refine the OSCAR content and survey
      methodology to document nursing home staffing information.

PMID- 15871870
TI  - A controlled, randomized, comparative study of a radiant heat bandage on the
      healing of stage 3-4 pressure ulcers: a pilot study.
AB  - OBJECTIVES: Pressure ulcers, like other chronic wounds, fail to proceed through
      an orderly and timely process to produce anatomical or functional integrity.
      Treatment of pressure ulcers is directed to improving host factors and providing
      an optimum wound environment. In addition to providing a moist wound environment,
      it has been theorized that preventing hypothermia in a wound and maintaining a
      normothermic state might improve wound healing. DESIGN/SETTING: Forty-one
      subjects with a stage 3 or stage 4 truncal pressure ulcer >1.0 cm(2) were
      recruited from outpatient clinics, long-term care nursing homes, and a
      rehabilitation center. The experimental group was randomized to a radiant-heat
      dressing device and the control group was randomized to a hydrocolloid dressing,
      with or without a calcium alginate filler. Subjects were followed until healed or
      for 12 weeks. RESULTS: Eight subjects (57%) in the experimental group had
      complete healing of their pressure ulcer compared with 7 subjects (44%) with
      complete healing in the control group (P = .46). CONCLUSION: Although a 13%
      difference in healing rate between the two arms of the study was found, this
      difference was not statistically significant. At almost all points along the
      healing curve, the proportion not healed was higher in the control arm.

PMID- 15871871
TI  - The effects of changes in nursing home staffing on pressure ulcer rates.
AB  - OBJECTIVE: To examine the relationships between various components of nursing
      home staffing (total staffing levels and staff mix, staff turnover, and changes
      in staffing patterns) to an important measure of quality, risk-adjusted rates of
      pressure ulcer development. DESIGN, SETTING, AND MEASUREMENTS: Staffing records
      from 35 Department of Veterans Affairs (DVA) nursing homes were reviewed and
      nursing home administrators from each of the facilities were interviewed.
      Incidence rates for pressure ulcers were obtained from DVA's national long-term
      care database and risk adjusted using patients' baseline characteristics. The
      relationships of risk-adjusted pressure ulcer rates to staffing patterns were
      tested. RESULTS: Although there was no linear association between staffing levels
      and pressure ulcer rates, data analysis revealed a strong trend (P = .07) that
      among the nursing homes meeting staffing guidelines, 60% were among the best
      performing. Ten nursing homes reduced staffing levels from their baseline levels
      at the beginning of the study and/or changed their staffing mix by replacing
      licensed personnel with nursing assistants. This change was associated with a
      2.1% higher rate of pressure ulcer development (P = .004). CONCLUSION: Changes in
      nursing home staffing patterns (either a decrease in overall staffing levels or a
      change in staffing mix) are related to the quality of nursing home care. Staff
      stability is associated with better outcomes.

PMID- 15871872
TI  - Fecal incontinence in older patients.
AB  - Fecal incontinence (FI), the involuntary passage of fecal material through the
      anus, is a common medical problem in older people, especially in frail older
      nursing home residents. FI is often associated with urinary incontinence. Severe
      constipation leading to fecal impaction, laxative abuse, diarrhea, cognitive
      impairment, senescence, and neuromuscular disorders including autonomic
      neuropathy, are among the leading causes of FI in older patients. FI affects
      patients' physical and psychological well-being, and is responsible for
      considerable morbidity and mortality in older patients. This results in
      significant healthcare costs. Comprehensive management of this disorder requires
      a systematic approach including thorough history, physical examination, and step
      wise evaluation. This review in contrast to others published in last decade,
      focuses on management of FI in frail older nursing home patients, who require an
      individualized approach, which should be minimally invasive and cost-effective.
      In many cases of FI, treatment of the underlying condition; adequate control of
      diarrhea, constipation, or fecal impaction; adjustment of medications; and proper
      feeding may control or reduce FI. Advanced tests are often not necessary in this
      population.

PMID- 15871873
TI  - Evaluation of an educational program for long-term care nursing assistants.
AB  - OBJECTIVES: To determine if an educational program can improve knowledge and
      attitude among ancillary staff on end-of-life care issues in a long-term care
      facility. DESIGN: A pilot study using a pre- and post-test design prior to and at
      the completion of an education intervention. SETTING: A long-term care facility
      in suburban Philadelphia that has 150 assisted living beds and 53 nursing home
      beds. PARTICIPANTS: Long-term care ancillary staff including certified nursing
      assistants (called "care managers" at this facility), social workers,
      recreational therapists, and food service workers. INTERVENTION: The intervention
      was a novel educational program consisting of five in-service lectures with
      accompanying take home self-study modules for ancillary staff in long-term care
      entitled "Dignity in Dementia." MEASUREMENTS: Ancillary staff attitudes and
      knowledge on end-of-life issues in dementia were assessed with a knowledge and
      attitude questionnaire pre- and post-intervention. One-year follow-up
      questionnaires were administered to assess long-term maintenance of knowledge and
      attitude changes. RESULTS: Thirty-two ancillary staff completed the pre
      intervention questionnaires. Twenty-nine ancillary staff completed the post
      intervention questionnaires (90.6%). There was a significant change in the end-of
      life knowledge level of the ancillary staff (P =.0270). Specifically, there was a
      significant change in one question dealing with dementia as a terminal disease (P
      = .006). There were also significant changes in the average attitude scores of
      the ancillary staff. (P = .0242). One-year follow-up revealed that both knowledge
      and attitude changes were maintained. CONCLUSIONS: This pilot project
      demonstrates that a staff educational program on end-of-life care for dementia
      residents can improve end-of-life knowledge and attitudes among long-term care
      ancillary staff and that this improvement can be maintained for up to 1 year.
      This intervention is easily reproducible in the long-term care setting. This
      project is an important step in helping improve end-of-life care for dementia
      residents in long-term care settings by improving the knowledge and attitudes of
      their caregivers.

PMID- 15871874
TI  - Establishing and educating a long-term care regional ethics committee: the NJ
      model.

PMID- 15871875
TI  - The NJ SEED project: evaluation of an innovative initiative for ethics training
      in nursing homes.
AB  - OBJECTIVES: This article reports the results of an evaluation of the New Jersey
      Stein Ethics Education and Development (NJ SEED) project--a statewide initiative
      to create, organize and educate a statewide network of regional long-term care
      ethics committees. The main focus of the evaluation was to measure utilization of
      the committees, describe how facilities have benefited from the project, and
      identify potential barriers to the use of this resource. METHODS: Based on
      administrative records from the NJ SEED project, 225 facilities were identified
      and asked to complete a facility survey. Ninety-three surveys were received,
      resulting in a 41% response rate. An additional survey of the regional ethics
      committees (RECs), as well as several focus groups and individual interviews were
      conducted to supplement the survey data. RESULTS: Fifty-eight percent of the
      facility respondents reported current participation in an NJ regional ethics
      committee. About one third (30%) of participating facilities had requested a
      formal case consultation (on at least one occasion) on behalf of a resident, but
      two thirds had consulted with their RECs on a more informal basis. Facilities
      that reported participating in the REC Network were more likely to have formally
      written policies than nonparticipants. CONCLUSIONS: Many NJ nursing homes find
      the statewide REC Network to be an important resource; however continued efforts
      need to be expended for recruiting and training facilities that are not taking
      full advantage of this important source of peer support and professional
      expertise.

PMID- 15871876
TI  - Warfarin monitoring: consider the three Ds.

PMID- 15871877
TI  - The mind-set of pain assessment.

PMID- 15871878
TI  - Overcoming a prejudice against qualitative studies.

PMID- 15871879
TI  - American Medical Directors Association and American Society of Consultant
      Pharmacists joint position statement on the Beers List of Potentially
      Inappropriate Medications in Older Adults.

PMID- 15871880
TI  - Feeding tube use in Italian nursing homes: the role of cultural factors.

PMID- 15871881
TI  - The free lunch and the literature.

PMID- 15871882
TI  - Project protect: pneumococcal vaccination in Washington State nursing homes.
AB  - BACKGROUND: Pneumonia is the third most frequent cause of hospitalization among
      Medicare beneficiaries in Washington State. While a vaccine against pneumococcal
      disease has been available since 1977, the 1999 Behavioral Risk Factor
      Surveillance System estimates that less than 60% of adults aged 65 years and
      older in Washington State have been vaccinated. METHODS: To assess the prevalence
      of pneumococcal vaccination policies, we surveyed all Washington nursing homes in
      1999 and again in 2001 to assess changes during the intervening period. Following
      the policy surveys, to estimate the pneumococcal vaccination rate, we conducted
      assessments of a random sample of residents of Washington nursing homes. RESULTS:
      Use of standing orders/written pneumococcal vaccination policies by nursing homes
      increased by 14% from 58% in 1999 to 72% in 2001. The pneumococcal vaccination
      rate for residents of nursing homes increased from 47% in 2000 to 61% in 2002.
      Both increases were statistically significant. The odds of a resident receiving a
      pneumococcal polysaccharide vaccine (PPV) in a nursing home having standing
      orders or other written guidelines are estimated to be two-and-a-half times
      greater than for residents in facilities without any PPV guidelines (2000: OR =
      2.59; 95% CI, 1.54-4.34; 2002: OR = 3.19; 95% CI, 1.68-6.01). CONCLUSION:
      Increased use of standing orders/written policies has contributed to higher rates
      of pneumococcal vaccination in Washington State nursing homes.

PMID- 15871883
TI  - Characteristics of long-term care facilities associated with standing order
      programs to deliver influenza and pneumococcal vaccinations to residents in 13
      states.
AB  - BACKGROUND: Standing order programs (SOPs) are effective evidence-based
      interventions in which nurses or pharmacists are authorized to vaccinate
      according to an approved protocol without a physician order or examination.
      National rates for influenza and pneumococcal vaccination in long-term care
      facilities (LTCF) are far below HP2010 goals of 90%. OBJECTIVES: The aim of this
      study was to describe the prevalence of SOPs and other types of immunization
      programs in LTCFs and determine characteristics of LTCFs implementing SOPs.
      DESIGN: Mailed survey. SETTING: All Medicare- or Medicaid-licensed LTCFs in 13
      states. PARTICIPANTS: Directors of Nursing (DONs). MEASUREMENTS: Survey
      collecting information on SOPs and barriers to their use in respondents' LTCF.
      Data from this survey were linked to the On-line Survey and Certification
      Administrative Record (OSCAR), a federal administrative database containing
      structural, staffing and other information on LTCFs. RESULTS: A total of 3,451 of
      4,366 (79%) LTCFs completed surveys. Few facilities used SOPs for influenza (9%)
      or pneumococcal vaccination (7%). The greatest use of influenza SOPs compared
      with other immunization program types were seen in facilities that were
      government owned or owned by nonprofit entities compared with for-profit entities
      (15% and 10% vs. 7%; odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5 to
      3.4 and OR = 1.4, CI = 1.1 to 1.8, respectively); dually-certified (both Medicare
      and Medicaid-certified) nursing facilities compared with distinct part skilled
      nursing facilities in which beds are set aside for residents with a specific
      payment source (11% vs. 7%; OR = 1.6, CI = 1.3 to 2.1); independent facility
      compared with one that is part of a multi-facility chain (10% vs. 7%; OR = 1.3,
      CI = 1.1 to 1.7); and lower acuity index (resident resource needs) compared with
      higher (10% vs. 7%; OR = 1.4, CI = 1.1 to 1.7). Findings were similar for
      pneumococcal vaccination SOPs. SOP use varied substantially by state (range = 0%
      to 23% influenza; range = 3% to 15% pneumococcal). The most frequently reported
      barriers to SOP use were legal concerns: liability for the facility (53%) and
      staff lacking legal authority (39%) to vaccinate by standing orders. CONCLUSIONS:
      Although LTCFs with certain characteristics used SOPs more often, overall few
      facilities (<10%) used SOPs to improve vaccination rates. SOP use varied by state
      indicating that state policies or other factors may promote or inhibit SOP use.
      More studies are needed to examine the causes of state-level variations in
      vaccination interventions and their relationships to health outcomes of residents
      in LTCFs. The federal government's resources to promote SOPs should focus on all
      LTCFs, but with a particular focus on those that are less likely to be using SOPs
      and that represent a large proportion of homes nationally (i.e., for-profit and
      chain facilities).

PMID- 15871884
TI  - Albumin, length of stay, and proton pump inhibitors: key factors in Clostridium
      difficile-associated disease in nursing home patients.
AB  - OBJECTIVES: To identify risk factors for Clostridium difficile-associated disease
      (CDAD) in nursing home patients. DESIGN: Retrospective chart reviews. SETTING:
      Long-term care facility with 347 beds and an additional 180 sub-acute care beds,
      adjacent to an academic tertiary care hospital center. PARTICIPANTS: Twenty-five
      patients had documented diagnosis of CDAD. Eighty-four percent were female, 76%
      white, 16% black, 4% Asian, and 4% Hispanic. Age ranged between 60 and 97 years
      (mean: 82.2 years). The control group had 28 patients, 68% were female, 89%
      white, and 11% black. Age ranged between 61 and 101 years (mean: 82.3 years).
      MEASUREMENTS: Length of stay at the facility, initial presenting symptoms, white
      blood cell count at the time of diagnosis, serum albumin level prior to the start
      of antibiotics, body mass index calculated from weight and height, presence or
      absence of dementia, history of diabetes mellitus and colonic disease, activity
      of daily living data include mobility, toileting and eating, use of percutaneous
      enterogastrostomy feeding, antibiotic administration, namely, type and duration,
      use of enema and laxatives, and use of proton pump inhibitors. RESULTS: Episodes
      of CDAD occurred mainly within the first year of admission to our facility, with
      a mean of 6 months, whereas the mean length of stay was 25 months in the control
      group (t = 3.452; df = 51; P < .01). Albumin level was another major risk factor
      for CDAD, with an overwhelming 68% of CDAD patients having albumin levels below 3
      g/dL (mean 2.68 g/dL) compared with a mean of 3.22 g/dL in the control group (t =
      4.210; df = 51; P < .001). The third significant risk factor was the use of
      proton pump inhibitors, 60% versus 32%, respectively (chi(2) = 4.137; df = 1; P <
      .05). Levofloxacin was the most frequently prescribed antibiotic (37%).
      Surprisingly, factors not associated with CDAD included dementia, diabetes
      mellitus, colonic disease, use of enema, use of laxatives, weight and body
      metabolic index, duration of previous antibiotic therapy for unrelated infection,
      mobility, toileting, and method of eating. CONCLUSION: A low albumin level, a
      recent admission to a nursing facility, and the use of proton pump inhibitors
      should be considered as probable risk factors for CDAD when assessing
      institutionalized patients with diarrhea. These findings may facilitate the
      timely and efficient management of CDAD in nursing home patients.

PMID- 15871885
TI  - Antimicrobial use in post-acute care: a retrospective descriptive analysis in
      seven long-term care facilities in Georgia.
AB  - BACKGROUND: Antimicrobial use in long-term care facilities (LTCF) is an important
      public health issue, especially regarding its potential role in antimicrobial
      resistance. Up to two thirds of long-stay LTCF residents receive antimicrobial
      therapy each year. However, little is known specifically about antimicrobial use
      in short-stay LTCF residents receiving post-acute care. METHODS: The authors
      conducted a retrospective chart review of a random sample of residents admitted
      for post-acute care in seven LTCFs in Georgia from September 1, 1999 to August
      31, 2000 to determine the rates and characteristics of antimicrobial prescribing
      in this population. RESULTS: Of 221 post-acute care residents, 105 (48%) received
      152 courses of antimicrobial therapy during their post-acute stay. At least one
      antimicrobial was prescribed on 796 of 5220 resident-days (15%). Antimicrobial
      therapy was split evenly between hospital-initiated antimicrobial therapy (n =
      53, 50%) and antimicrobial therapy initiated in the LTCF during post-acute care
      (n = 52, 50%). Levofloxacin was the most commonly prescribed antimicrobial. Where
      documentation on the suspected infection was present, the most common infections
      were urinary tract infections (UTIs) and pneumonias. For residents with post
      acute care-initiated therapy, documentation regarding the presumed source of
      infection was absent for 44% of antimicrobial prescriptions. Most antimicrobial
      courses initiated for presumed infections in post-acute care were by telephone
      orders (66%). CONCLUSIONS: Utilization of antimicrobial therapy in LTCF residents
      in post-acute care is relatively high and may be greater than for long-stay LTCF
      residents. For hospital-initiated therapy, improved communication between
      hospital and LTCF staff may improve documentation and antimicrobial therapy in
      LTC. For antimicrobial therapy initiated by telephone orders in post-acute care,
      improving documentation of suspected source of infection is needed.

PMID- 15871886
TI  - Association of knowledge of adult protective services legislation with rates of
      reporting of abuse in Iowa nursing homes.
AB  - OBJECTIVE: To determine if there is an association between abuse reporting to
      state authorities by nursing home administrators and directors of nursing and
      their characteristics and knowledge of the law. DESIGN: Survey. SETTING: Iowa's
      409 Medicare certified nursing homes. PARTICIPANTS: Four hundred nine
      administrators and 409 directors of nursing. MEASUREMENTS: Nursing home abuse
      incidents, reports, and substantiations, Medicare's Nursing Home Compare Reports,
      Urban Influence Codes, and county census demographics. RESULTS: A single or
      double response was received from 369 (90%) of the 409 nursing homes. Being a
      male administrator and having a higher level of education is associated with
      higher substantiation rates. A greater knowledge of the dependent adult
      protective services law is associated with higher incident and report rates for
      directors of nursing. CONCLUSIONS: Nursing home administrators' and directors of
      nursing's knowledge of the law and their characteristics are associated with
      nursing home incident, report, and substantiation of abuse allegations.

PMID- 15871887
TI  - Functional Incidental Training: applicability and feasibility in the Veterans
      Affairs nursing home patient population.
AB  - OBJECTIVE: To examine the applicability and feasibility of an intervention
      directed at improving continence, endurance, and strength (Functional Incidental
      Training [FIT]), for older patients in Veterans Administration (VA) nursing
      homes. DESIGN: Data were collected during a randomized, controlled, crossover
      trial. SETTING: Four VA nursing homes. PARTICIPANTS: All 528 patients in the
      nursing homes were screened, 178 were eligible, and 107 were randomized into the
      trial. A total of 64 participants completed the intervention phase of the trial.
      INTERVENTION: Trained research staff provided the FIT intervention, which
      included prompted voiding combined with individualized, functionally oriented
      endurance and strength training exercises offered four times per day, 5 days per
      week, for 8 weeks. MEASURES: Descriptive data were collected relevant to the
      translation of the FIT intervention into everyday practice, including number of
      patients eligible and reasons for ineligibility, attrition rates and reasons for
      attrition, participant adherence to and satisfaction with FIT, and the costs of
      FIT relative to usual care. RESULTS: One third of the 528 patients met the
      eligibility criteria. The major reasons for ineligibility were being continent,
      age under 60, and a short anticipated length of stay. Of the 146 patients
      enrolled in the trial, 85 (58%) dropped out during the 9- to 10-month project.
      Deterioration in health status, death, and discharge accounted for two thirds of
      the attrition. Adherence to FIT was in general high but variable. Participants
      completed prompted voiding plus at least one exercise in 75% of the FIT rounds
      offered. Of the 60 participants who completed the protocol and who could answer
      simple questions, 75% indicated they enjoyed FIT, but 62% indicated that the
      exercise was too frequent, and 28% indicated they were offered opportunities to
      toilet too often. Based on timed observations, the costs of FIT are about four
      times as high as usual continence care. CONCLUSIONS: FIT is applicable to a
      substantial number of patients in VA nursing homes. The FIT protocol tested in
      this trial can be further refined and individualized based on patient preferences
      and adherence to various components of FIT in order to make it more feasible,
      efficient, and cost-effective in practice. The costs of maintaining an
      intervention such as FIT in all VA nursing home patients who may benefit,
      however, are high and must be justified largely by potential positive effects on
      function and quality of life, as opposed to cost savings resulting from the
      intervention.

PMID- 15871888
TI  - Predictors of anticoagulation prescription in nursing home residents with atrial
      fibrillation.
AB  - OBJECTIVES: To determine predictors of oral anticoagulation (OAC) for atrial
      fibrillation (AF) in long-term care (LTC). DESIGN: Chart review. SETTING: Six LTC
      facilities in a metropolitan area. PARTICIPANTS: One hundred seventeen residents
      with AF identified from 934 total residents. MEASUREMENTS: Data was obtained from
      the medical chart, pharmacy record, and Minimum Data Set (MDS) regarding
      demographics, medical conditions, falls, fractures, gastrointestinal bleeding
      (GIB), peptic ulcer disease, dementia, anemia, and physical/cognitive function
      scales. The recursive partition algorithm was used to construct a model
      reflecting physician decision patterns that predict prescription of OAC. RESULTS:
      Among those 117 residents (12.5% of 934) who had AF (age, 84.6 +/- 8 years), OAC
      was prescribed for 54 (46%); aspirin or clopidogrel: 47 (40%); neither OAC nor
      any antithrombotic treatment (ATT): 25 (21%). Prior stroke was the primary
      determinant of OAC. Residents with prior stroke were less likely to be prescribed
      OAC if they had prior GIB, were non-Caucasian, or had no history of coronary
      artery disease (CAD). Those without a stroke were less likely to be prescribed
      OAC if they were younger, had dementia or lower functional status. CONCLUSION:
      Prior stroke was the primary predictor of OAC use. Our model suggests that
      physicians may also incorporate concerns of age, bleeding, cognitive and physical
      function, and ethnicity into the decision-making process. Further study is needed
      to explore the reasons why 21% of the residents receive neither OAC nor ATT, and
      why OAC may be less likely to be prescribed to non-Caucasian LTC residents.

PMID- 15871889
TI  - An approach to endemic multi-drug-resistant bacteria in nursing homes.

PMID- 15871890
TI  - Methods of pain assessment in residents of long-term care facilities: a pilot
      study.
AB  - OBJECTIVES: Structured programs for routine pain assessment and treatment are
      necessary to optimize care for residents of long-term care facilities (LTCFs). A
      pilot study was designed to develop, implement, and evaluate a system for pain
      assessment and monitoring in a LTCF. Additional goals were to determine whether a
      verbal and/or non-verbal tool adequately assess pain in residents of LTCFs and
      whether the pharmacologic therapy for pain changes with the implementation of a
      pain assessment and monitoring system. DESIGN: Quantitative, nonexperimental
      design using two pain assessment tools. SETTING: The study was conducted at a
      LTCF in a rural midwestern setting. PARTICIPANTS: The study population for phase
      I included residents on any pain medication (regularly scheduled or as needed) on
      the secure dementia unit. The target population for phase II consisted of
      residents on any pain medication on an open unit. INTERVENTION: Training was
      provided to the nursing staff on how to use two pain assessment tools, one verbal
      (colored visual analog scale) and one nonverbal (observed pain target behaviors),
      and documentation. In addition, a continuing education program on pain assessment
      and management in elderly residents and barriers to pain management in LTCFs was
      offered to medical providers. MEASUREMENTS: Evaluation with the colored visual
      analog scale (CVAS) occurred twice daily. Pain target behaviors were monitored
      throughout the day and recorded by nursing staff at the end of each shift. All
      residents in the study population were monitored daily for six months. RESULTS:
      Most of the residents on both units were unable to use the verbal tool; however,
      the nonverbal tool was used successfully for all residents studied. On the
      dementia unit, the use of pain medications increased, and pain target behaviors
      decreased during the study period; on the open unit, the use of pain medications
      remained stable, and pain target behaviors decreased. CONCLUSION: These data
      suggest that an increase in awareness of pain may facilitate an improvement in
      the assessment and management of pain in residents of LTCFs. The feasibility of
      the nonverbal pain monitoring method shown in this study has positive
      implications on quality of care issues if generalizable to a larger population.

PMID- 15871891
TI  - Preventing antimicrobial-resistant bacterial infections among older adults in
      long-term care facilities.
AB  - For older adults in long-term care facilities (LTCFs), the rate of infections
      caused by antimicrobial resistant strains of bacteria has increased and is
      prompting renewed interest in investing health care resources for prevention and
      control of these pathogens. This document offers a simple framework to combat
      infections due to antimicrobial resistant bacteria in LTCF residents by providing
      a multi-step approach consisting of four major strategies: prevent infection,
      diagnose and treat infection effectively, use antimicrobials wisely, and prevent
      transmission. Recommendations from this multi-step approach are directed at LTCF
      medical directors and practicing clinicians involved with the medical care of
      older adult LTCF residents.

PMID- 15871892
TI  - If we were supposed to take vitamins, wouldn't they grow on trees?
AB  - Vitamin E supplementation may not be as innocuous as previously believed. A dose
      relationship between vitamin E and all-cause mortality may exist, beginning at
      150 IU per day. Mortality risk was minimally but statistically higher for doses
      of Vitamin E 1000 IU/d or greater compared with placebo. Further controlled
      trials using both natural and synthetic forms of Vitamin E are warranted to
      determine the true effects.

PMID- 15871893
TI  - Pharmacokinetic interaction and erythromycin-induced sudden cardiac death:
      implications for practice.

PMID- 15871895
TI  - Residents' care preferences as targeting criteria: measurement issues functional
      incidental training: applicability and feasibility in the Veterans Affairs
      nursing home patient population.

PMID- 15871896
TI  - Is law good therapy for institutional adult abuse?

PMID- 15871897
TI  - Updated National Cholesterol Education Program III guidelines.

PMID- 15871898
TI  - The hospitalist: creating a patient-focused paradigm for a change.

PMID- 15871899
TI  - Errors in a research article published in a peer-reviewed scholarly journal.

PMID- 15871901
TI  - Evidence-based medicine in long-term care.

PMID- 15871902
TI  - Mortality among male veterans with hip fractures.

PMID- 15871903
TI  - Effects of transforming growth factor beta1 (TGFbeta-1) and dentin non
      collagenous proteins (DNCP) on human embryonic ectomesenchymal cells in a three
      dimensional culture system.
AB  - Cranial neural crest-derived ectomesenchymal cells represent a population of
      pluripotent stem cells giving rise to many of the various oro-facial and dental
      tissues. The factors determining the terminal fate of these cells are still
      unclear. The potentiality of human embryonic ectomesenchymal cells from the first
      branchial arch have been investigated when isolated and grown in a three
      dimensional (3D)-collagen gel culture system in the presence of dentin matrix
      derived non-collagenous proteins (DNCP) and TGFbeta-1. Functional differentiation
      of cells showing some characteristics of odontoblast-like cells could be observed
      when the cells were cultured with DNCP+TGFbeta-1 or DNCP, however, only
      cytological differentiation was observed during culture with TGFbeta-1 alone. The
      characteristics of these cells was assessed by morphological appearance,
      expression of the odontoblast phenotype marker dentin sialophosphoprotein (DSPP),
      increased alkaline phosphatase levels and formation of mineralised nodules in
      vitro. The results indicate that these embryonic cells from the first branchial
      arch are capable of responding to the inductive stimulus of DNCP or DNCP+TGFbeta
      1 when isolated and grown in the 3D collagen gel culture system. The capacity of
      the isolated cells to differentiate into mineralizing cells showing some
      characteristics of odontoblast-like cells under these growth conditions
      highlights the potential of such approaches for tissue engineering strategies for
      hard-tissue regeneration after injury.

PMID- 15871904
TI  - IFNgamma regulates PDGF-receptor alpha expression in macrophages, THP-1 cells,
      and arterial smooth muscle cells.
AB  - The recruitment of monocyte-derived macrophages (MDMs) and arterial smooth muscle
      cells (ASMCs) contributes to inflammation and development of intimal hyperplasia
      during atherosclerosis. Platelet-derived growth factor (PDGF) is a potent mitogen
      for SMC, signalling through PDGF-receptor subunits alpha (Ralpha) and beta
      (Rbeta). We have previously found that interferon gamma (IFNgamma) upregulates
      PDGF-Ralpha mRNA expression in human MDM (hMDM) which causes an increased
      migration towards PDGF. In the present study, we found that IFNgamma mediated an
      upregulation of PDGF-Ralpha mRNA also in THP-1 cells. The induction of PDGF
      Ralpha in both hMDM and THP-1 cells was caused by STAT1 binding to the PDGF
      Ralpha promoter. In human ASMCs, IFNgamma again stimulated a transient STAT1
      binding to the PDGF-Ralpha promoter. However, this was not followed by an
      upregulation of PDGF-Ralpha mRNA. IFNgamma-stimulation resulted in augmented
      expression of PDGF-Ralpha protein in differentiated hMDM. Early hMDM only
      expressed an immature and not fully glycosylated form of the PDGF-Ralpha protein.
      In contrast, THP-1 cells did not synthesize PDGF-Ralpha protein, implying further
      posttranscriptional inhibition. Our results contribute to a better understanding
      of the complex regulation of PDGF-Ralpha expression and how proinflammatory
      factors may contribute to PDGF-related hyperplasia in vascular diseases.

PMID- 15871905
TI  - IRF-1 and NF-kappaB p50/cRel bind to distinct regions of the proximal murine IL
      12 p35 promoter during costimulation with IFN-gamma and LPS.
AB  - LPS and IFN-gamma, which activate NF-kappaB cRel/p50 and IFN regulatory factor-1
      (IRF-1), respectively, costimulate expression of the IL-12 p35 subunit in
      macrophages. The murine p35 promoter proximal to exon 2 is active during
      costimulation with IFN-gamma and LPS because it contains kappaB and IRF elements
      (E) with significant homology to the human p35 promoter. IFN-gamma or LPS
      stimulate nuclear localization of IRF-1 or cRel/p50, respectively, in the RAW
      264.7 macrophage cell line. EMSAs reveal that IFN-gamma/LPS stimulates within 2
      h, in RAW 264.7 cells or peritoneal macrophages, nuclear localization of proteins
      that target nt -137/-93 of the p35 promoter. DNA affinity assays utilizing
      nuclear extracts from RAW 264.7 cells show that NF-kappaB cRel and p50 bind to
      the kappaB-E within nt -122 to -93 of the p35 exon 2 promoter while IRF-1 binds
      to the IRF-E within nt -157 to -113 but not the one within nt -122 to -93. In
      addition, p50/cRel attachment to the kappaB-E was not dependent upon IRF-1
      association with the IRF-E, and vice versa. Chromosome immunoprecipitation assays
      confirm inducible recruitment of IRF-1 and cRel to the endogenous p35 exon 2
      promoter in both RAW 264.7 and primary macrophages costimulated with IFN-gamma
      and LPS. IFN-gamma, IFNgamma/LPS, or overexpression of IRF-1 plus cRel activated
      the wild-type p35 promoter reporter but not the p35 promoter reporter mutated at
      nt -110/-101 or in the presence of IRF-1 siRNA. Thus, cRel with IRF-1 induce p35
      expression through a small region of the p35 exon 2 promoter during IFN-gamma and
      LPS costimulation of macrophages.

PMID- 15871906
TI  - Cytogenetic biomonitoring in children with chronic tonsillitis: micronucleus
      frequency in exfoliated buccal epithelium cells.
AB  - OBJECTIVE: To investigate the possible harmful cytogenetic effects associated
      with chronic tonsillitis by analyzing the micronucleus frequency and other
      nuclear abnormalities in exfoliated buccal epithelial cells. MATERIALS AND
      METHODS: The study consisted of 20 children with chronic tonsillitis, and 20
      control subjects with similar age and sex. The ages ranged between 5 and 12 years
      old (mean age: 7.5). The patients were diagnosed as having chronic tonsillitis on
      the basis of history, throat culture and clinical examinations. Buccal cell
      samples were collected with a wooden spatula. The samples were then applied to
      clean microscope slides. Smears were air dried and fixed in methanol:acetic acid.
      Then slides were stained by the Feulgen reaction technique. Three slides were
      prepared for each subject and 1000 cells were evaluated per slide to determine
      the frequencies of micronucleus and other nuclear abnormalities (binucleats,
      karyorrhexis and karyolysis). Statistically, Mann-Whitney U-test was used to
      analyze and compare the data. RESULTS: The mean micronucleus frequencies in
      patient and control groups were 5.29+/-1.67 and 1.58+/-0.33, respectively. In the
      patient group, mean binucleus, karyorrhexis and karyolysis frequencies were
      3.13+/-1.2, 2.04+/-0.64, and 1.74+/-0.47, respectively. However, in the control
      group, mean binucleus, karyorrhexis and karyolysis frequencies were 1.43+/-0.47,
      1.26+/-0.45, and 0.88+/-0.27, respectively. The mean frequencies of all
      parameters in the patient group were higher than the control values, and the
      difference was found to be statistically significant (p<0.001). CONCLUSION: Our
      results revealed that children with chronic tonsillitis could be under risk of
      significant cytogenetic damage.

PMID- 15871907
TI  - Optimization of a genotypic assay applicable to all human immunodeficiency virus
      type 1 protease and reverse transcriptase subtypes.
AB  - Genotypic assays are used often to guide clinicians in decisions concerning the
      treatment of patients. An optimized sequence-based genotypic assay was used to
      determine the whole protease and reverse transcriptase (RT) gene, including the
      gag cleavage site region and RNase H region. Since non-B subtypes are increasing
      in countries where subtype B was the most prevalent subtype, and treatment
      becomes more available in developing countries where the epidemic is
      characterized by a high prevalence of non-B subtypes, it was important that the
      genotypic test was evaluated using a panel of different subtypes. Amplification
      was successful for different subtypes: A, B, C, D, F, G, H, J, CRF01_AE,
      CRF02_AG, CRF11_cpx, CRF13_cpx and an uncharacterized recombinant sample. The
      detection limit of the PCR was 1000 copies/ml, except for 1 subtype C sample
      (PL3) and 1 CRF02_AG sample (PL8). The detection limit for these samples was 5000
      copies/ml. A sequence could be obtained in both directions for most of the
      samples.

PMID- 15871908
TI  - Detection of vitellogenin and zona radiata protein expressions in surface mucus
      of immature juvenile Atlantic salmon (Salmo salar) exposed to waterborne
      nonylphenol.
AB  - Induction of blood plasma vitellogenin (Vtg) and zona radiata proteins (Zr
      proteins) in male and juvenile of oviparous vertebrates was proposed and shown to
      be sensitive biomarkers for exposure to estrogen mimic. The time- and dose
      dependent expression of Vtg and Zr-proteins in nonylphenol (NP) exposed juvenile
      Atlantic salmon (Salmo salar) is reported. Fish were exposed continuously to
      waterborne nonylphenol at 5, 15 and 50 microg/L. Blood and surface mucus samples
      were collected after 3 and 7 days post-exposure. Nonylphenol-induced plasma and
      surface mucus levels of Vtg and Zr-protein were analysed using immunochemical
      methods (Western blot and enzyme-linked immunosorbent assay; ELISA). Both Vtg and
      Zr-protein levels in plasma and surface mucus showed similar and parallel
      nonylphenol-induced expression patterns after waterborne nonylphenol exposure and
      in a concentration- and time-dependent manner. Zr-proteins were significantly
      induced at the lowest concentration of nonylphenol after 3 and 7 days of exposure
      both in plasma and in surface mucus. We conclude that the detection of Vtg and Zr
      proteins directly in the surface mucus of fish, and the correlation of these
      values with plasma protein biomarker values in xenoestrogen-treated fish
      represents a sensitive non-invasive system for the detection of these known
      endocrine disruptor biomarkers. The demonstration of detectable Vtg and Zr
      protein levels from surface mucus is a potential biomarker for estrogenic
      compounds, and their presence should be considered as an improvement in the
      methods for detection of endocrine disrupting chemicals (EDCs) and related
      pollutants in the environment.

PMID- 15871909
TI  - Steps of the tick-borne encephalitis virus replication cycle that affect
      neuropathogenesis.
AB  - Tick-borne encephalitis virus (TBEV) is an important human pathogen that causes
      severe neurological illness in large areas of Europe and Asia. The
      neuropathogenesis of this disease agent is determined by its capacity to enter
      the central nervous system (CNS) after peripheral inoculation
      ("neuroinvasiveness") and its ability to replicate and cause damage within the
      CNS ("neurovirulence"). TBEV is a small, enveloped flavivirus with an
      unsegmented, positive-stranded RNA genome. Mutations affecting various steps of
      its natural replication cycle were shown to influence its neuropathogenic
      properties. This review describes experimental approaches and summarizes results
      on molecular determinants of neurovirulence and neuroinvasiveness that have been
      identified for this virus. It focuses on molecular mechanisms of three particular
      steps of the viral life cycle that have been studied in some detail for TBEV and
      two closely related tick-borne flaviviruses (Louping ill virus (LIV) and Langat
      virus (LGTV)), namely (i) the envelope protein E and its role in viral attachment
      to the cell surface, (ii) the 3'-noncoding region of the genome and its
      importance for viral RNA replication, and (iii) the capsid protein C and its role
      in the assembly process of infectious virus particles. Mutations affecting each
      of these three molecular targets significantly influence neuropathogenesis of
      TBEV, particularly its neuroinvasiveness. The understanding of molecular
      determinants of TBEV neuropathogenesis is relevant for vaccine development, also
      against other flaviviruses.

PMID- 15871911
TI  - Demonstration of polymorphism among Brucella ovis field isolates by pulsed-field
      gel electrophoresis.
AB  - Brucella ovis is recognized worldwide as an important pathogen of sheep, and has
      also been identified in farmed deer in New Zealand. Previously, only one strain
      type of B. ovis has been identified. The objective of this paper was to perform
      pulsed-field gel electrophoresis (PFGE) on field isolates of B. ovis to determine
      whether strain variations exist, whether sheep and deer are affected by the same
      strains, and to compare the performance of the rare-cutting restriction enzymes
      XbaI and SwaI. Ten B. ovis isolates from sheep and two from deer in New Zealand,
      as well as the type strain, were subjected to PFGE analysis using both XbaI and
      SwaI. PFGE of XbaI restriction fragments produced two banding patterns consisting
      of 27-28 bands, which were found to be 98% similar by cluster analysis, and were
      named X1 and X1a. PFGE of SwaI restriction fragments resulted in three banding
      patterns consisting of 13-15 bands each. Ten of the isolates had identical
      banding patterns and were named S1. One isolate differed by one band,
      representing a subtype named S1a. Two isolates differed by six bands,
      representing a different strain type of B. ovis and this was named S2. Cluster
      analysis showed S2 to be 78% similar to the S1/S1a cluster. Both strain types
      were isolated from both sheep and deer. Thus, two distinct strain types of B.
      ovis were identified in New Zealand, which is the first report of more than one
      strain type being identified worldwide. Neither strain was species-specific for
      sheep or deer. The restriction endonuclease SwaI was found to be more
      discriminatory than the enzyme XbaI, which has been used in previous studies.

PMID- 15871910
TI  - Stepholidine protects against H2O2 neurotoxicity in rat cortical neurons by
      activation of Akt.
AB  - The fundamental pathological process(es) associated with schizophrenia (SZ)
      remain(s) uncertain, but multiple lines of evidence suggest that this condition
      is associated with excessive stimulation of striatal dopamine (DA) D2 receptors,
      deficient stimulation of medial prefrontal cortex (mPFC) D1 receptors as well as
      neuronal apoptosis. Unlike typical antipsychotics, stepholidine (SPD), which is
      isolated from the Chinese herb stephania, has D1 and D2 dual properties and
      regulates neuronal cell differentiation and proliferation. It is unknown,
      however, whether it possesses a neuroprotective property. Here, we report that
      SPD prevented neuronal cell death from H2O2 exposure and increased the levels of
      phosphorylated Akt (pAkt), a serine/threonine protein kinase. The SPD-induced
      neuroprotection and activation of Akt were blocked by LY294002, a PI3-K
      inhibitor, suggesting that the anti-apoptotic action of SPD is mediated via the
      PI3-K/Akt signaling pathway. Thus, as a survival or anti-apoptotic factor for
      neuronal cells, SPD may contribute to the therapeutic action of SPD in SZ
      treatment.

PMID- 15871913
TI  - A novel method for generation of signature networks as biomarkers from complex
      high throughput data.
AB  - Traditionally, gene signatures are statistically deduced from large gene
      expression and proteomics datasets and have been applied as an experimental
      molecular diagnostic technique that is sensitive to experimental design and
      statistical treatment. We have developed and applied the approach of "signature
      networks" which overcomes some of the drawbacks of clustering methods. We have
      demonstrated signature network assembly, functional analysis and logical
      operations on the networks that can be generated. In addition, we have used this
      technique in a proof of concept study to compare the effect of differential drug
      treatment using 4-hydroxytamoxifen and estrogen on the MCF-7 breast cancer cell
      line from a previously published study. We have shown that the two compounds can
      be differentiated by the networks of interacting genes. Both networks consist of
      a core module of genes including c-Fos as part of c-Fos/c-Jun heterodimer and c
      Myc which is clearly visible. Using algorithms in our MetaCore software we are
      able to subtract the 4-hydroxytamoxifen and estrogen networks to further
      understand differences between these two treatments and show that the estrogen
      network is assembled around the core with other modules essential for all phases
      of the cell cycle. For example, Cyclin D1 is present in networks for the estrogen
      treated cells from two separate studies. These signature networks represent an
      approach to identify biomarkers and a general approach for discovering new
      relationships in complex high throughput toxicology data.

PMID- 15871912
TI  - Differences in DNA-damage in non-smoking men and women exposed to environmental
      tobacco smoke (ETS).
AB  - There is much data implicating environmental tobacco smoke (ETS) in the
      development and progression of disease, notably cancer, yet the mechanisms for
      this remain unclear. As ETS is both a pro-oxidant stressor and carcinogen, we
      investigated the relationship of ETS exposure to intracellular and serum levels
      of DNA-damage, both oxidative 8-hydroxy-2-deoxyguanosine (8OHdG) and general, in
      non-smokers from non-smoking households, occupationally exposed to ETS. General
      DNA-damage consisting of single and double strand breaks, alkali-labile sites and
      incomplete base-excision repair, increased significantly in a dose-dependent
      manner with ETS exposure in men (P=0.015, n=32, Pearson) but not women (P=0.736,
      n=17). Intracellular 8OHdG-DNA-damage and general DNA-damage were both greater in
      men than women (P=0.0005 and 0.016, respectively) but 8OHdG serum levels did not
      differ between the genders. Neither 8OHdG-DNA-damage nor serum levels correlated
      with increasing ETS exposure. This is the first study to demonstrate dose
      dependent increases in DNA-damage from workplace ETS exposure. Perhaps most
      interesting was that despite equivalent ETS exposure, significantly greater DNA
      damage occurred in men than women. These data may begin to provide a mechanistic
      rationale for the generally higher incidence of some diseases in males due to
      tobacco smoke and/or other genotoxic stressors.

PMID- 15871914
TI  - Pro-inflammatory cytokine gene expression and nitric oxide regulation of aqueous
      extracted Astragali radix in RAW 264.7 macrophage cells.
AB  - Astragali radix, which has tonifying and circulatory effect as well as immune
      response, is one of the oldest and most frequently used crude drug for oriental
      medicine in many Asian countries. The present study was conducted to evaluate the
      effect of aqueous extract of Astragali radix (ARE) on the functions of murine
      macrophage cell line, RAW 264.7 macrophage cells. In the cell proliferation
      assay, methotrexate (MTX), an agent of immune suppression, decreased the cell
      proliferation of RAW 264.7 macrophage cells (IC(50): 100 microg/ml), but the
      suppression of cell proliferation was significantly protected by ARE treatment in
      RAW 264.7 macrophage cells. The expressions of cytokine gene by ARE were
      investigated using reverse transcription polymerase chain reaction (RT-PCR). In
      RT-PCR, IL-1alpha, IL-1beta and IL-6 mRNA expressions was induced in ARE-treated
      RAW 264.7 macrophage cells. We also investigated the effect of the nitric oxide
      (NO) synthesis and inducible nitric oxide synthase (iNOS) mRNA expression by ARE.
      ARE alone had no effect on NO synthesis and iNOS mRNA expression in RAW 264.7
      cells. In the case of lipopolysaccharide (LPS) stimulation, NO production and
      iNOS mRNA expression were detected in RAW 264.7 cells. However, NO production and
      iNOS mRNA expression which is induced by LPS decreased after treatment of ARE.
      These data demonstrate that ARE can reduce the suppression of macrophage cell
      proliferation induced by MTX, and induce IL-1alpha, IL-1beta and IL-6 mRNA
      expressions in RAW 264.7 macrophage cells. Also, ARE inhibit NO production in LPS
      stimulated RAW 264.7 macrophage cells, and the inhibition of NO production may be
      associated with the inhibition of iNOS mRNA expression.

PMID- 15871915
TI  - Optimization and validation of a fully automated silica-coated magnetic beads
      purification technology in forensics.
AB  - Automated procedures for forensic DNA analyses are essential not only for large
      throughput sample preparation, but are also needed to avoid errors during routine
      sample preparation. The most critical stage in PCR-based forensic analysis is DNA
      isolation, which should yield as much highly purified DNA as possible. The
      extraction method used consists of pre-treatment of stains and samples, cell
      lysis using chaotropic reagents, binding of the DNA to silica-coated magnetic
      particles, followed by elution of the DNA. Our work focuses mainly on sample
      preparation, obtaining the maximum possible amount of biological material from
      forensic samples, and the following cell lysis, to create a simple standardized
      lysis protocol suitable for nearly all forensic material. After optimization and
      validation, the M-48 BioRobot((R)) workstation has been used for more than 20,000
      routine lab samples. There has been no evidence of cross contamination. Resulting
      DNA from as small as three nuclear cells yield reliable complete STR
      amplification profiles. The DNA remains stable after 2 years of storage.

PMID- 15871916
TI  - Ion-suppression effects in liquid chromatography-tandem mass spectrometry due to
      a formulation agent, a case study in drug discovery bioanalysis.
AB  - Liquid chromatography-tandem mass spectrometry (LC/MS/MS) has become the
      technology of choice for bioanalysis, due to its high selectivity and high sample
      throughput. However, concerns have grown that this technique may be subject to
      errors due to "invisible" interferences, in particular ion-suppression.
      Investigations on ion-suppression from formulation agents have only been
      published to a limited extent. Such effects can be of particular importance in
      pre-clinical discovery studies where drugs may be formulated with large amount of
      solubilisers and bioanalysis may use fast generic methods. In a preliminary
      pharmacokinetic study we observed strong ion-suppression from a polysorbate co
      solvent, which, if undetected, would have given highly erroneous pharmacokinetic
      results and possibly could have led to the inappropriate elimination of a
      promising drug candidate. Different chromatographic methods were tested
      indicating that the separation step was essential in controlling these effects. A
      method based on matrix dilution is proposed to check for these effects during the
      use of discovery support methods, where full validation is not practical. Some
      excipients commonly used in formulations are polydispersed polymers, for which
      very limited pharmacokinetic information is available. Further investigation is
      needed to better understand the mechanisms of ion-suppression and the kinetics of
      the suppressing species to allow the development of new LC/MS/MS based analytical
      strategies, which will not be subject to such ionisation interferences.

PMID- 15871917
TI  - Hair cycle-specific expression of versican in human hair follicles.
AB  - BACKGROUND: Versican, a large chondroitin sulfate proteoglycan molecule, is
      implicated in the induction of hair morphogenesis, the initiation of hair
      regeneration, and the maintenance of hair growth in mouse species. In contrast,
      in human hair follicles, the distribution and the roles of versican remains
      obscure. OBJECTIVES: To elucidate the implication of versican in normal human
      hair growth. METHODS: Versican expression was examined by in situ hybridization
      (mRNA) and immunohistochemistry (protein). RESULTS: The results clearly showed
      specific versican gene expression in the dermal papilla of anagen, which
      apparently decreased in the dermal papilla of catagen hair follicles. No specific
      signal was detectable in telogen hair follicles. Consistent with ISH results,
      versican immunoreactivity was extended over the dermal papilla of anagen hair
      follicles, and again, this staining diminished in the catagen phase of human hair
      follicles. Interestingly, versican proteins were deposited outside K15-positive
      epithelial cells in the bulge throughout the hair cycle. Versican
      immunoreactivity in the dermal papilla was almost lost in vellus-like hair
      follicles affected by male pattern baldness. CONCLUSION: Specific expression of
      versican in the anagen hair follicles suggests its importance to maintain the
      normal growing phase of human as well as mouse.

PMID- 15871918
TI  - Susceptibility of Borrelia afzelii strains to antimicrobial agents.
AB  - The aim of the present study was to determine the susceptibility of Borrelia
      afzelii strains to antibiotics, and to test the hypothesis that persistence of
      borrelia in skin, after therapy, is a consequence of resistance to the antibiotic
      used for treatment. Ten B. afzelii strains isolated from skin of seven adult
      patients (two with acrodermatitis chronica atrophicans, five with erythema
      migrans) were studied. In three patients B. afzelii was isolated from erythema
      migrans lesion before antibiotic therapy and 2-3 months after treatment with
      cefuroxime axetil (two patients) or with ceftriaxone (one patient). MICs and MBCs
      for amoxicillin, azithromycin, ceftriaxone, cefuroxime, doxycycline and amikacin
      were measured. There was total resistance to amikacin but isolates were
      susceptible to all other antibiotics except one isolate that was resistant to
      cefuroxime, MIC > 4 mg/L. Comparison of MBC values after 3 and 6 weeks'
      incubation revealed comparable results for azithromycin and ceftriaxone while for
      amoxicillin, cefuroxime and doxycycline, some differences were found. In one of
      the patients from whom there were borrelia isolated before and after treatment
      with cefuroxime axetil, both isolates were resistant to cefuroxime. In the other
      two patients, the paired isolates were susceptible to the antibiotic used for
      therapy.

PMID- 15871920
TI  - Simultaneous voltammetric measurement of ascorbic acid, epinephrine and uric acid
      at a glassy carbon electrode modified with caffeic acid.
AB  - A stable electroactive thin film of poly(caffeic acid) has been deposited on the
      surface of a glassy carbon electrode by potentiostatic technique in an aqueous
      solution containing caffeic acid. Poly(caffeic acid) was used as a modified
      electrode for the detection of ascorbic acid (AA), epinephrine (EP), uric acid
      (UA) and their mixture by cyclic voltammetry. This modified electrode exhibits
      potent and persistent electron-mediating behavior followed by well-separated
      oxidation peaks towards AA, EP and UA with activation overpotential. For the
      ternary mixture containing AA, EP and UA, the three compounds can well separate
      from each other at the scan rate of 20 mVs(-1) with a potential difference of
      156, 132 and 288 mV between AA and EP, EP and UA and AA and UA, respectively,
      which was large enough to determine AA, EP and UA individually and
      simultaneously. The catalytic peak current obtained, was linearly dependent on
      the AA, EP and UA concentrations in the range of 2.0 x 10(-5) to 1.0 x 10(-3) mol
      l(-1), 2.0 x 10(-6) to 8.0 x 10(-5) mol l(-1) and 5.0 x 10(-6) to 3.0 x 10(-4)
      mol l(-1), and the detection limits for AA, EP and UA were 7.0 x 10(-6), 2.0 x
      10(-7) and 6.0 x 10(-7) mol l(-1), respectively. The modified electrode shows
      good sensitivity, selectivity and stability, and has been applied to the
      determination of EP in practical injection samples and that of EP, UA and AA
      simultaneously with satisfactory results.

PMID- 15871919
TI  - Hand-held monitor of sympathetic nervous system using salivary amylase activity
      and its validation by driver fatigue assessment.
AB  - In order to realize a hand-held monitor of the sympathetic nervous system, we
      fabricated a completely automated analytical system for salivary amylase activity
      using a dry-chemistry system. This was made possible by the fabrication of a
      disposable test-strip equipped with built-in collecting and reagent papers and an
      automatic saliva transfer device. In order to cancel out the effects of
      variations in environmental temperature and pH of saliva, temperature- and pH
      adjusted equations were experimentally determined, and each theoretical value was
      input into the memory of the hand-held monitor. Within a range of salivary
      amylase activity between 10 and 140 kU/l, the calibration curve for the hand-held
      monitor showed a coefficient with R(2)=0.97. Accordingly, it was demonstrated
      that the hand-held monitor enabled a user to automatically measure the salivary
      amylase activity with high accuracy with only 30 microl sample of saliva within a
      minute from collection to completion of the measurement. In order to make
      individual variations of salivary amylase activity negligible during driver
      fatigue assessment, a normalized equation was proposed. The normalized salivary
      amylase activity correlated with the mental and physical fatigue states. Thus,
      this study demonstrated that an excellent hand-held monitor with an algorithm for
      normalization of individuals' differences in salivary amylase activity, which
      could be easily and quickly used for evaluating the activity of the sympathetic
      nervous system at any time. Furthermore, it is suggested that the salivary
      amylase activity might be used as a better index for psychological research.

PMID- 15871921
TI  - Epileptic seizures, epilepsy and epileptic syndromes in newborns: a nosological
      approach to 94 new cases by the 2001 proposed diagnostic scheme for people with
      epileptic seizures and with epilepsy.
AB  - PURPOSE: To assess the advantages of the 2001 ILAE proposed diagnostic scheme for
      classification of newborns with epileptic seizures over the 1989 ILAE
      classification. METHOD: Clinical features, seizure semiology and duration,
      neurological evaluation, ictal and interictal EEG, brain imaging and outcome at
      the end of the neonatal period (44 weeks post-conceptional age) of 94 newborns
      with EEG confirmed seizures were analyzed. The 2001 ILAE classification was
      applied where possible. RESULTS: Twenty patients died before the end of the
      neonatal period. In the remaining patients, applying axis 3, we classified 54
      newborns as having epileptic seizures that do not require a diagnosis of
      epilepsy; 14 as symptomatic partial epilepsy; 5 within the neonatal epileptic
      syndromes and one as benign neonatal seizures (NS). Axis 4 in all newborns
      provided a valuable tool in order to better define the individual patient.
      CONCLUSIONS: Compared to the 1989 ILAE classification, which allowed a syndromic
      diagnosis in only 6/94 patients, the remaining being classified as Epilepsies and
      Syndromes undetermined whether focal or generalized, the 2001 ILAE diagnostic
      scheme, applied at the end of the neonatal period, offers a variety of approaches
      to classification, allowing an early distinction between epilepsy and single or
      isolated clusters of seizures, with therapeutic and prognostic implications.

PMID- 15871922
TI  - BMP signaling and early embryonic patterning.
AB  - Bone morphogenetic proteins (BMPs) play pleiotropic roles during embryonic
      development as well as throughout life. Recent genetic approaches especially
      using the mouse gene knockout system revealed that BMP signaling is greatly
      involved in early embryonic patterning, which is a dynamic event to establish
      three-dimensional polarities. The purpose of this review is to describe the
      diverse function of BMPs through different receptor signaling systems during
      embryonic patterning including gastrulation and establishment of the left-right
      asymmetry.

PMID- 15871923
TI  - BMP receptor signaling: transcriptional targets, regulation of signals, and
      signaling cross-talk.
AB  - Bone morphogenetic proteins (BMPs), members of the transforming growth factor
      beta (TGF-beta) superfamily, bind to two different serine/threonine kinase
      receptors, and mediate their signals through Smad-dependent and Smad-independent
      pathways. Receptor regulated-Smad (R-Smad) proteins specific for the BMP pathways
      interact with various proteins, including transcription factor Runx, and transmit
      specific signals in target cells. The recent development of DNA microarray
      techniques has allowed us to identify many BMP target genes. BMP signaling is
      modulated by various molecules, including inhibitory Smads (I-Smads). Moreover,
      recent findings have revealed that BMP pathways interact with other signaling
      pathways, and such signaling cross-talk plays pivotal roles in growth and
      differentiation of target cells.

PMID- 15871925
TI  - Respiratory muscle plasticity.
AB  - Plasticity of respiratory muscles must be considered in the context of their
      unique physiological demands. The continuous rhythmic activation of respiratory
      muscles makes them among the most active in the body. Respiratory muscles,
      especially the diaphragm, are non-weight-bearing, and thus, in contrast to limb
      muscles, are not exposed to gravitational effects. Perturbations in normal
      activation and load known to induce plasticity in limb muscles may not cause
      similar adaptations in respiratory muscles. In this review, we explore the
      structural and functional properties of the diaphragm muscle and their response
      to alterations in load and activity. Overall, relatively modest changes in
      diaphragm structural and functional properties occur in response to perturbations
      in load or activity. However, disruptions in the normal influence of phrenic
      innervation by frank denervation, tetrodotoxin nerve block and spinal
      hemisection, induce profound changes in the diaphragm, indicating the substantial
      trophic influence of phrenic motoneurons on diaphragm muscle.

PMID- 15871927
TI  - The geriatric interdisciplinary team training (GITT) program.
AB  - Geriatric interdisciplinary team training (GITT) is an initiative funded by the
      John A. Hartford Foundation since 1995. Building from the substantial knowledge
      gained from the Veteran's Administration project in interdisciplinary team
      training and lessons from the Pew Foundation initiative, GITT was reconceived by
      the Foundation to address the need for teams in the care of older adults in the
      new era of managed care and health care cost containment. This training program
      has served to help us understand attitudes toward teams, how teams function, and
      how teams should be trained in the changing health care environment, where length
      of stay is dramatically different from the earlier team training projects. This
      introductory paper provides an overview of GITT, and the companion papers give
      detail of the GITT curricula, measures and lessons learned.

PMID- 15871928
TI  - Organizational issues in establishing geriatrics interdisciplinary team training.
AB  - The John A. Hartford Foundation-supported geriatrics interdisciplinary team
      training (GITT) initiative was a bold attempt to create a new educational agenda
      for the health professions. Although some components of GITT were previously in
      place at the eight institutions that participated in the Hartford initiative and
      at other institutions (e.g., Department of Veterans Affairs), never before has
      geriatrics interdisciplinary team training been so systematically planned,
      implemented, or evaluated. This paper focuses on four organizational factors
      essential to the establishment of a geriatrics interdisciplinary team training
      program: (1) organizational readiness to implement GITT, including the needs and
      existing resources of the organization; (2) partnerships, specifically the
      relationships between academic and clinical organizations; (3) institutional
      support, the tangible and intangible sources of support necessary at multiple
      levels within the organization; and (4) structure, the administrative and
      organizational requirements for team training programs. An analysis of these four
      factors and the influences upon them can help facilitate the successful
      implementation of interdisciplinary training programs at institutions considering
      this educational approach.

PMID- 15871929
TI  - Organizational structure, team process, and future directions of
      interprofessional health care teams.
AB  - For a nationwide Geriatric Interdisciplinary Team Training (GITT) program
      evaluation of 8 sites and 26 teams, team evaluators developed a quantitative and
      qualitative team observation scale (TOS), examining structure, process, and
      outcome, with specific focus on the training function. Qualitative data provided
      an important expansion of quantitative data, highlighting positive effects that
      were not statistically significant, such as role modeling and training occurring
      within the clinical team. Qualitative data could also identify "too much" of a
      coded variable, such as time spent in individual team members' assessments and
      treatment plans. As healthcare organizations have increasing demands for
      productivity and changing reimbursement, traditional models of teamwork, with
      large teams and structured meetings, may no longer be as functional as they once
      were. To meet these constraints and to train students in teamwork, teams of the
      future will have to make choices, from developing and setting specific models to
      increasing the use of information technology to create virtual teams. Both
      quantitative and qualitative data will be needed to evaluate these new types of
      teams and the important outcomes they produce.

PMID- 15871930
TI  - Frail older patient care by interdisciplinary teams: a primer for generalists.
AB  - Frail older patients-unlike younger persons in the health care system or even
      well elders-require complex care. Most frail older patients have multiple chronic
      illnesses. Optimum care cannot be achieved by following the paradigm of ongoing
      traditional health care, which emphasizes disease and cure. Because no one health
      care professional can possibly have all of the specialized skills required to
      implement such a model of health care delivery, interdisciplinary team care has
      evolved. This paper describes the roles of the participating team members in the
      context of interdisciplinary care for frail older adults. In addition, the
      challenges that occur when Geriatric Interdisciplinary (ID) Teams involved in
      providing care to frail older patients are identified and discussed.

PMID- 15871931
TI  - Using case studies to evaluate students' ability to develop a geriatric
      interdisciplinary care plan.
AB  - The Geriatric Interdisciplinary Team Training (GITT) program, an educational
      intervention funded by The John A. Hartford Foundation of New York City, has
      trained more than 1800 health care professions students and clinicians throughout
      the United States. Evaluating the effectiveness of this training intervention has
      proven to be quite a challenge. Core measures were collected pre- and post-GITT
      training to evaluate student development as a result of GITT. This paper focuses
      on one of these core measures, the Test of Geriatric Interdisciplinary Care
      Planning (TGICP). This instrument, developed for the GITT program, is one
      mechanism created to test trainees' ability to develop an interdisciplinary plan
      of care. Using a case study methodology, this two-part instrument provides an
      innovative approach to quantifying and correlating responses from an
      interdisciplinary cohort of students. This paper will describe the development of
      the TGICP, including the creation and validation of the case studies, the
      framework for the questionnaire, and the coding and scoring mechanism created to
      evaluate trainee responses.

PMID- 15871932
TI  - Using scripted video to assess interdisciplinary team effectiveness training
      outcomes.
AB  - As part of the Geriatric Interdisciplinary Team Training (GITT) Program funded by
      the John A. Hartford Foundation, the authors of this article worked to create an
      instrument, the Trainee Test of Team Dynamics, to assess health care trainees'
      understanding of team dynamics. The Trainee Test of Team Dynamics is a five
      question written test designed to capture GITT trainees' knowledge of team
      process and skills in addressing conflict that is administered after watching a
      five-minute videotape of a simulated interdisciplinary health care team meeting.
      The test was created to measure health professions students' abilities to
      recognize effective geriatric health care teams, to respond to effective and
      ineffective team behaviors, and to determine whether or not the team meeting
      achieved its purpose: to meet the patient's needs for an interdisciplinary care
      plan. Scripts and test items developed and tested by practitioners in social
      work, medicine, public health, nursing and others assured a product that
      compensated for differences in educational level and occupation, yet captured
      accurate and appropriate responses. The results reported here include an analysis
      of 740 trainees' baseline responses from the multi-site educational programs to
      determine the construct validity of the new measure.

PMID- 15871933
TI  - Assessing geriatrics in undergraduate medical education: two different
      approaches.
AB  - Most medical schools do not have a separate course in geriatrics, but rather
      incorporate geriatrics into existing courses. Tracking and assessing curriculum
      content is more difficult in this setting. This paper describes and compares two
      approaches to assess curriculum content in geriatrics: a survey of course
      directors and a course objectives review. The results suggest that course
      directors report more geriatric content when asked as part of a regular survey
      than they identify as specific course objectives. Course objectives may be more
      reflective of the actual emphasis placed on aging-related material in courses.
      These two approaches appear to be complementary. Medical educators may find both
      self-report and course objective analysis to be useful and complementary in
      tracking geriatric material in the undergraduate medical curriculum.

PMID- 15871934
TI  - Improving medical care of persons with Alzheimer disease through clinical
      teaching: the IMPACT program.
AB  - The purpose of this project was to develop, implement, evaluate, and disseminate
      an educational program on ethics and the primary care of patients with dementia
      for residents. Pre/post-rotation self-confidence measure, a post-rotation
      assessment of the importance of and achievement of the program's goals, and a
      post-rotation evaluation of the program were administered. Significant increases
      in residents' confidence in performing the programmatic clinical goals and in
      overall confidence were found. Program goals were met, and components of the
      program were rated highly. We found that a well-designed ethics curriculum can be
      successfully implemented within a clinical rotation for medicine residents and
      have a positive impact on the quality of the educational experience as well as on
      their confidence in performing relevant clinical management behaviors.

PMID- 15871935
TI  - Developing a training program on issues in aging for correctional workers.
AB  - Older adults who are incarcerated and living in prisons represent an increasing,
      yet invisible, group among the aging population. Two factors in particular have
      contributed to this growth: the aging of the general population and the
      escalating number of prisoners serving long sentences. Working effectively with
      older inmates poses a challenge for correctional workers who are accustomed to
      dealing with a much younger clientele. In many states, correctional employees are
      required to obtain annual training, and educational institutions can play a major
      role in providing the expertise necessary in the development of quality training
      materials on issues related to aging. While continuing education programs to
      address the needs of workers in community-based and long-term care settings have
      grown rapidly, they have made negligible progress in more obscure settings such
      as prisons. This paper discusses the development of a 6-hour training program
      entitled "Issues in Aging for Correctional Workers." The training was developed
      through the interdisciplinary collaborative efforts of two faculty members who
      teach in the criminal justice and sociology/social work departments at a medium
      sized liberal arts university in the upper Midwest.

PMID- 15871936
TI  - A workshop for nursing home staff: recognizing and responding to their own and
      resident's emotions.
AB  - An appreciation for the emotion work required of nursing home staff suggests that
      caregiver education should address the skills of emotional intelligence. Although
      the number of training efforts geared toward paraprofessionals is growing, few
      programs address caregivers' emotional skills, and fewer still have their roots
      in research. After providing background on resident-centered care, caring for the
      caregiver, and emotions in dementia, this paper describes a research-based
      workshop that promotes nursing home staff's skills in emotional intelligence. The
      first segment of the workshop introduces the importance of being aware of one's
      feelings and controlling impulses, and discusses how to manage one's own
      emotions. The second segment focuses on recognizing residents' emotions and
      helping residents manage their emotions.

PMID- 15871937
TI  - The development of an educational collaborative to address comprehensive pressure
      ulcer prevention and treatment.
AB  - The prevention and treatment of pressure ulcers is a growing public policy
      concern. Driven by a more informed consumer and the exploding costs of care,
      policy makers are looking for ways to integrate health-care research and long
      term care practices in an effort to improve the quality of care and ultimately
      reduce costs. This paper presents a case study that demonstrates how training is
      being integrated at the facility level, utilizing a collaborative. The
      collaborative was a joint public-private partnership supported through resources
      from state, federal, and private agencies, with an overarching goal of delivering
      high-quality, easily accessible geriatric education and training. Direct care
      providers and other practitioners were recruited to attend a live, interactive
      videoconference that featured nationally known experts. The content of the
      educational program was drawn from nationally accepted guidelines that discuss
      appropriate procedures for wound cleansing, dressings, positioning techniques,
      proper nutrition and risk assessment protocols. Evaluation of the program
      indicated that the highest-rated objectives related to the application of
      training content in the implementation of treatment and prevention procedures
      important to quality patient care. An examination of publicly available data
      revealed that an escalating increase in the percentage of facilities in the state
      cited for deficiencies because of the incidence of pressure ulcers from 1996 to
      1999 was reversed in 2000, subsequent to the videoconference. Future programs are
      planned to sustain the availability of opportunities for practitioners to get
      critical updates from the experts in the field via live interactive sessions.

PMID- 15871938
TI  - Aging in introductory and life cycle nutrition textbooks.
AB  - The aging content in 11 undergraduate nutrition textbooks (8 introductory, 3 life
      cycle) was evaluated using content analysis. Repeated measures ANOVAs with
      Bonferroni post hoc procedures and t- tests were used. The 259 relevant pages
      largely focused on geriatrics (physiological decline, chronic diseases).
      Gerontological aspects were underemphasized. Mean number of pages on aging was
      significantly higher in life cycle (M = 37) than in introductory textbooks (M =
      18), t (9) = 3.42, p < .008. In introductory textbooks, mean percentage of pages
      on aging (M = 3.2%) was significantly less than for maternal (M = 4.6%) and
      childhood topics (M = 6.2%), p < .05. Overall, topic omissions included
      discussion of ageism, death, dying, and dignity; and end-of-life decisions
      related to nutrition and hydration. Women and minorities were proportionately
      represented in generally positive photographs. Aging terminology was 81% neutral
      (older, aging), 14% negative (impaired, senile), and 5% positive (active,
      independent). These textbooks may not help students acquire the broad knowledge
      needed to work with older adults or develop positive attitudes about aging.
      Recommendations for authors, publishers, and instructors are provided.

PMID- 15871939
TI  - Challenges of current geriatric education-inspired by the Nordic geriatric
      professors' meetings.
AB  - Geriatric educators are faced with several different challenges. The rapid growth
      of aged population in the Western world has led to a growing need for health and
      social services and thus, an increased need for trained professionals in this
      field. In addition, new learning theories and activating learning methods have
      achieved wide acceptance in academic medicine. How has geriatric education
      applied these new learning methods? In this article we review the current status
      of academic geriatric education in Western countries in these respects. We
      especially review the literature of how geriatric training has been experimenting
      with the new learning methods.

PMID- 15871940
TI  - Investigating the factor structure of an instrument to measure attitudes and
      preparedness to work with elders with Alzheimer's disease.
AB  - This study investigated the factor structure of an instrument to measure
      attitudes and preparedness of social work students to work with memory-impaired
      elders. Exploratory statistical procedures to reduce data through principle
      component analysis identified three factors with eigenvalues greater than 1.0 and
      a cumulative variance of 65.520%. These factors include general belief in the
      efficacy of psychotherapeutic services for elders with memory impairment; self
      perceived adequacy to provide services to elders with memory impairment; and
      belief in the efficacy of other ancillary services to elders with memory
      impairment. Recommendations are made for utilizing this brief self-report
      instrument in training and assessing students and other practitioners for their
      attitudes toward and greater preparedness to work with memory- impaired elders.

PMID- 15871941
TI  - Effect of service-learning on knowledge about older people and faculty teaching
      evaluations in a physical therapy class.
AB  - The major purpose of this study was to identify the knowledge, misconceptions,
      and bias regarding aging among graduate physical therapy students and to
      determine whether service-learning modified any of these variables. A cohort of
      40 students in a graduate physical therapy program was randomly divided into an
      experimental (service-learning) or control (no service-learning) group. General
      knowledge and attitudes about aging were measured by Palmore's Facts on Aging
      Quiz I. The Wilson Student Evaluation of Faculty tool measured student
      evaluations of a faculty member at the end of the semester. Two-way analyses of
      variance with repeated measures revealed that all students increased their
      knowledge about aging, p < .05. However, students who initially had negative
      attitudes toward older adults significantly improved their attitudes only after
      the service-learning experience, p < .05. A t-test revealed that teaching
      evaluation scores were significantly lower in the service-learning course, p <
      .05. The results suggest that service-learning effectively enhanced both the
      knowledge and attitudes of physical therapy students toward the older adult.
      Although service-learning imparted better learning for the student, there was
      some risk to the faculty member as evidenced by lower teaching evaluations.

PMID- 15871942
TI  - Combining lifelong learning with civic engagement: a university-based model.
AB  - What role can and should the university play in enhancing the civic engagement of
      the fifty-plus population? The interest on the part of this population in
      lifelong learning has already been demonstrated to be a priority. There is also a
      growing movement for increasing the engagement of universities with their local
      communities, including expanded service-learning opportunities for college
      students and faculty. Can universities build upon these two areas of growth to
      create a format that will assist in the recruitment and retention of older
      volunteers? The University of Maryland has been testing variations of a model
      that combines lifelong learning, leadership development, and civic engagement in
      both the United States and Europe. A version of this civic engagement model is
      presented as a replicable model that can pioneer new methods of civic engagement
      both for older adults and for universities.

PMID- 15871943
TI  - A model for developing a gerontology curriculum module in small baccalaureate
      social work programs.
AB  - A model is described that infuses a gerontology curriculum module into an
      existing baccalaureate social work practicum seminar by tapping existing
      resources in the aging services network. Particularly practical in small
      programs, this model utilizes community practitioners in the aging services
      network as instructors for the gerontology curriculum module. Geriatric practice
      needs a focus on all levels of systems, and baccalaureate social workers bring a
      professional orientation that addresses the well-being of individuals and
      society. As practitioners in the aging services network work closely with social
      work programs in projects such as this model, there is increased opportunity to
      articulate the role of baccalaureate social workers in the field of aging as well
      as strengthen the gerontology competencies of baccalaureate social workers.

PMID- 15871944
TI  - Grandparents and grandchildren: a "memory box" course assignment.
AB  - Grandparents want to share family stories and memories with grandchildren.
      Implementing a classroom "memory box" assignment, allows grandparents and
      grandchildren a structured opportunity to discuss and explore family memories.
      What types of information do grandparents want to share with their grandchildren?
      This course assignment was implemented with college age students in a gerontology
      course with 100 grandparents to explore the types of memories they would like to
      leave with their grandchildren. Topics discussed were family history, family
      stories, grandparent's role, and advice grandparents would give to their
      grandchildren. Common themes that emerged suggested that grandparents wanted
      their grandchildren to know the importance of love in the family, spirituality,
      and morals such as honesty and trust. The "memory box" class assignment provides
      teachers and faculty with an educational learning exercise that can be
      incorporated into a current course to provide an intergenerational gerontology
      component into their curriculum.

PMID- 15871946
TI  - The International Journal of Lower Extremity Wounds. Why another?

PMID- 15871947
TI  - Hyperhomocysteinemia and venous thrombosis.
AB  - Deep vein thrombosis (DVT) leads to venous ulcers in later life. Venous ulcers
      are the majority of chronic lower extremity wounds. Recent evidence suggests that
      hyperhomocysteinemia is an independent risk factor for venous thrombosis. Other
      evidence suggests that dietary supplementation with folic acids and vitamins
      helps to change hyperhomocysteinemia. This may be the key to wound management in
      future.

PMID- 15871945
TI  - Activation of Nur77 by selected 1,1-Bis(3'-indolyl)-1-(p-substituted
      phenyl)methanes induces apoptosis through nuclear pathways.
AB  - Nur77 is an orphan receptor and a member of the nerve growth factor-I-B subfamily
      of the nuclear receptor family of transcription factors. Based on the results of
      transactivation assays in pancreatic and other cancer cell lines, we have now
      identified for the first time Nur77 agonists typified by 1,1-bis(3-indolyl)-1-(p
      anisyl)methane that activate GAL4-Nur77 chimeras expressing wild-type and the
      ligand binding domain (E/F) of Nur77. In Panc-28 pancreatic cancer cells, Nur77
      agonists activate the nuclear receptor, and downstream responses include
      decreased cell survival and induction of cell death pathways, including tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) and poly(ADP-ribose)
      polymerase (PARP) cleavage. Moreover, the transactivation and apoptotic responses
      are also induced in other pancreatic, prostate, and breast cancer cells that
      express Nur77. In Panc-28 cells, small inhibitory RNA for Nur77 reverses ligand
      dependent transactivation and induction of TRAIL and PARP cleavage. Nur77
      agonists also inhibit tumor growth in vivo in athymic mice bearing Panc-28 cell
      xenografts. These results identify compounds that activate Nur77 through the
      ligand binding domain and show that ligand-dependent activation of Nur77 through
      nuclear pathways in cancer cells induces cell death and these compounds are a
      novel class of anticancer agents.

PMID- 15871948
TI  - Four-layer bandaging: from concept to practice.
AB  - The 4-layer bandage was originally designed to provide sustained leg compression
      to patients with venous leg ulcers. Since then, the practice of 4-layer bandaging
      has become widespread in the United Kingdom. Ulcer healing rates vary for a
      number of reasons. This review, by a member of the original design team, seeks to
      discuss reasons of varying success and offers advice for its appropriate usage.

PMID- 15871949
TI  - Using living skin equivalents for diabetic foot ulceration.
AB  - Diabetic foot ulcers are a major clinical challenge with enormous socioeconomic
      consequence. All advances in the understanding and management of this problem are
      eagerly received by wound specialists. The development of bioengineered skin-
      living skin equivalent--is an interesting event that could be significant in the
      management of lower extremity wounds such as the diabetic foot ulcer.

PMID- 15871950
TI  - The radiological investigation and treatment of the critically ischemic limb--a
      review.
AB  - The contribution of radiological investigation and treatment in the management of
      the critically ischemic lower limb is reviewed. The methods of classifying and
      assessing the cause, level, and severity of the arterial disease causing the
      ischemia are discussed with comparison of the relative merits of the various
      invasive and noninvasive techniques of investigation. The development of the
      methods of interventional radiological management is described with an indication
      of the relative success of the different techniques. Newer interventional
      developments, including intravascular brachytherapy and gene therapy are
      discussed.

PMID- 15871951
TI  - Pyoderma gangrenosum.
AB  - Pyoderma Gangrenosum is cutaneous manifestation of a systemic problem that should
      be systematically diagnosed and managed with care. When such lesions appear on
      legs, it is important to study and treat the systematic problem.

PMID- 15871952
TI  - Systemic vasculitis.
AB  - The systemic vasculitides are a heterogeneous group of disorders characterized by
      inflammation of blood vessel walls. They can be classified according to the size
      of vessel affected and also into primary de novo vasculitides and secondary to
      other disease processes. Treatments differ and overlap depending on the type of
      vasculitis. It is therefore important to make the correct diagnosis and treat
      appropriately to achieve remission as there is a substantial mortality
      implication.

PMID- 15871953
TI  - Leg ulcers in the tropics.
AB  - Leg ulcers are an important clinical condition and are often difficult to treat.
      The treatment has to continue for long periods, and the associated morbidity
      leads to significant loss of work. The successful treatment of leg ulcers or
      chronic wounds depends upon accurate diagnosis and treatment of the underlying
      cause. In Western societies, most leg ulcers are due to venous insufficiency,
      arterial disease, neuropathy (usually diabetic), or some combination of these
      factors. In tropical countries, however, there have been no large series of leg
      ulcers reported. The prevalence of leg ulcers and etiology are unknown. In this
      article, a short review is presented of the etiology and management of lower
      extremity ulcers as seen in the tropical countries.

PMID- 15871954
TI  - Common denominators for the low-cost management of leg conditions.
AB  - Diseases of blood supply and drainage of the leg are common, and they frequently
      contribute to poverty. Management must include self-help low-cost therapy. The
      phlebologist, lymphologist, angiologist, or dermatologist must seek to distill
      their knowledge for the health worker in the general health services. Such
      knowledge should focus on the venous system, which is amenable to simple
      maneuvers such as breathing, elevation, and movement. However, the mechanisms
      underlying the functions of the blood vessels and lymphatics and the organ they
      supply or drain are inextricably interwoven. Care of the veins, the lymphatics,
      and the epidermis depends on attention to each together and at the same time. New
      knowledge of cytokines produced by the epidermis and their effects on
      angiogenesis and permeability suggest that care of the epidermis by washing and
      emollients has equal value as elevation and movement. Such maneuvers cost little
      and are usually available.

PMID- 15871955
TI  - Quantification and stratification: wound research in the future.
AB  - Advances in wound healing have been slow--from the realization of a concept
      through to its adoption into clinical practice. There are well-known and
      understood reasons for this conservative approach. One less well-tried thought is
      to stratify the patient's physiological status with regard to the wound. This may
      be the key to quantify changes in wound milieu and therefore to progress.

PMID- 15871957
TI  - Dermal changes in the lower leg skin of patients with venous hypertension.
AB  - Patients with chronic venous disease may develop characteristic changes in the
      skin of the lower limb known as lipodermatosclerosis (LDS). The affected skin
      becomes indurated and pigmented and often ulcerates. The degree of induration
      associated with LDS correlates directly with ulcer formation and leads to a
      subsequent delayed rate of healing. However, there is limited information
      regarding the cellular and molecular events that lead from venous dysfunction to
      LDS development. This article reviews the current knowledge of the clinical
      progression of chronic venous disease, summarizing the histological findings from
      these authors' laboratory and other studies on LDS, and offers possible
      mechanisms to explain the fibrotic changes associated with this condition.

PMID- 15871958
TI  - Debridement of the diabetic foot: a podiatric perspective.
AB  - High plantar pressures are a risk factor for diabetic foot ulcers that are common
      chronic wounds. In patients with peripheral neuropathy, plantar ulcers may be
      managed by debridement of callus, a process that has been shown to reduce peak
      plantar pressures. Callus debridement is clearly an important ulcer prevention
      strategy. The scalpel skills used by the podiatrist to remove callus are best
      suited to achieve safe, local sharp wound debridement. Current podiatric practice
      in the United Kingdom is based on sound theoretical principles. However, good
      scientific data recommending its efficacy are scarce. The role of podiatry in
      debridement and wound management needs careful examination, a major aim of this
      article.

PMID- 15871959
TI  - Optical pedobarography for assessing neuropathic feet in diabetic patients--a
      review.
AB  - The use of optical pedobarography is presented in this article. The limitations
      of the analytical methods using peak pressures as a parameter for assessment of
      foot at risk of plantar ulcers are indicated. A new method, which takes into
      consideration the actual plantar pressure distribution using the power ratio PR
      (the ratio of high-frequency power to the total power in the walking foot
      pressure image distribution)and relates it to 3 levels of sensation loss is
      described. PR is able to detect early loss of foot sensation characterized by a
      loss of sensation level of 4.5 gm. The methods available in the literature for
      management of foot ulcers by proper footwear design, and their limitations, are
      discussed. A new method of individualized footwear based on matching the softness
      of the footwear insole with the softness of normal foot sole soft tissue (having
      durometer reading of 20 degrees Shore) and optimum insole thickness (12 mm) is
      helpful in the prevention of plantar ulcers.

PMID- 15871960
TI  - Models to study ischemia in chronic wounds.
AB  - Wound healing is a complex immune response designed to achieve tissue repair
      following injury. Imbalance of stimulating and inhibiting factors cause failure
      of healing. Ischemia is a major cause of wound repair dysregulation and may be
      limb and life threatening. Investigating ischemic wound healing using animal
      models minimizes the complex accompanying factors that are usually present in
      humans, such as age or diabetes. This paper presents a limited review on normal
      physiological healing and on models that are used to study compromised healing
      under ischemic conditions.

PMID- 15871961
TI  - Phantom limb pain--a complication of lower extremity wound management.
AB  - Amputation is one treatment option for patients with critical limb ischemia,
      diabetic foot wounds, and occasionally, even venous leg ulcers. Amputation of the
      whole limb or part of it or the digits can cause complications including pain.
      Post-amputation pain, and especially phantom limb pain (PLP), is a poorly
      understood phenomenon. Effective management of established pain is a major
      challenge. This review is for wound workers who are a multiprofessional group.
      Any amputated limb, appendage, or viscera can be affected by PLP,though the focus
      of this article will be the treatment of PLP following limb loss. The
      pathophysiology is still not fully understood. The size of the problem of PLP,
      possible underlying physiological mechanisms, and potential preventative measures
      are presented in this article.

PMID- 15871962
TI  - Prevalence of mixed infections in the diabetic pedal wound: a perspective based
      on a national audit.
AB  - Foot infections can have disastrous consequences in the life of a diabetic. The
      treatment of the pedal wound demands a great deal of resources. This
      retrospective study was formulated to determine the incidence of polymicrobial
      infections. The National Hospital Discharge Survey was used to gather data
      regarding cultures from diabetic foot infections. Codes from surgery were used
      because intraoperative cultures are the most reliable. It was observed that
      Staphylococcus Aureus is the most frequently responsible inciting organism;
      regarding polymicrobial infections, Staphylococcus and Streptococcus were the
      most common combination found. Incidence of anaerobes and gram negatives was low.
      This information tells a clinician that very broad-spectrum antibiotics would
      most commonly not be necessary, putting the impetus on the doctors to clinically
      assess a wound and prescribe the most appropriate antibiotic selection.

PMID- 15871963
TI  - Maggot debridement therapy for chronic wounds.
AB  - This article presents a general overview of maggot debridement therapy, as used
      in the management of chronic infected wounds. Much has been written about this
      treatment method, both historically and in the past decade. Current clinical
      practice is discussed and clinical and laboratory research are reviewed, with
      attention to the inherent challenges of such research. The nature of microbial
      and fungal bio-film formation in chronic wounds is considered, although little is
      yet known of the extent and characterization of this phenomenon. The prospects
      for the future are addressed. These include the need for globally acceptable
      criteria for clinical outcomes and guidelines for "best practice," together with
      the pressing need for appropriately structured randomized controlled studies.

PMID- 15871964
TI  - Maggot therapy for foot and leg wounds.
AB  - Maggot debridement therapy has been used for more than 70 years to treat
      nonhealing soft tissue wounds. Blowfly larvae are used to debride, disinfect, and
      promote healing of chronic wounds. The use of maggot therapy is on the rise,
      owing to recognized limitations in our current medical and surgical wound care
      options. Anecdotal evidence of maggot therapy efficacy is plentiful, but large
      prospective comparative clinical trials are desperately needed. Until data from
      such studies become available, treatment criteria and safety data must be derived
      from retrospective studies, case series, and other published accounts. Based on
      these limited sources of data,treatment guidelines are proposed for the safe and
      effective use of maggots for treating problematic foot and leg wounds.

PMID- 15871965
TI  - Chronic wound management.

PMID- 15871966
TI  - Electromagnetic fields for bone healing.
AB  - Electrical stimulation has been applied in a number of different ways to
      influence tissue healing. Most of the early work was carried out by orthopedic
      surgeons looking for new ways of enhancing fracture healing, particularly those
      fractures that had developed into nonunions. Electrical energy can be supplied to
      a fracture by direct application of electrodes or inducing current by use of
      pulsed electromagnetic field or capacitive coupling. Many of these techniques
      have not been standardized, so interpretation of the literature can be difficult
      and misleading. Despite this, there have been a few good laboratory and clinical
      studies to investigate the effect of electrical stimulation on fracture healing,
      which are reviewed. These do not permit recommendation or rejection of the
      technique per se; however, there is some room for optimism. The authors present
      some of the guidelines for using this treatment modality but suggest that all
      treatment should be carried out as part of a clinical trial in order to generate
      reliable data.

PMID- 15871967
TI  - Noninvasive measurement techniques for monitoring of microvascular function in
      the diabetic foot.
AB  - There are, currently, 3 established clinical techniques routinely employed to
      determine the risk of ulceration in the diabetic foot. These are assessment of
      the circulation, the nervous control of sensation, and foot sensitivity to
      loading. Macrovascular measurements are used to assess sufficiency of the
      arterial supply to the foot. Evaluation of somatic neuropathy provides an
      indication of loss of plantar sensation. Skin pressure measurements indicate
      abnormalities in plantar loading. This combined approach is effective in allowing
      preventative measures to be applied prior to the onset of ulceration. In
      contrast, clinical measurement of microvascular function in the diabetic foot is
      uncommon. Indeed, there remains uncertainty regarding the importance of micro
      vascular complications in the development of foot ulcers. This is in part due to
      the difficulty of making in vivo measurements of microvascular function. This
      article evaluates 3 noninvasive measurement techniques for routine microvascular
      assessment of the diabetic foot: transcutaneous oxygen tension, laser Doppler
      flowmetry, and near-infrared spectroscopy. These techniques can be used to obtain
      useful parameters of microvascular function including surface oxygen,blood flow,
      intracellular oxygenation, and cellular respiration. In principle, such
      measurements can be related to underlying pathophysiology, for example,
      microangiopathy or autonomic neuropathy. This article considers how these general
      techniques can be adapted to support routine clinical measurement of
      microvascular function, particularly in the neuropathic diabetic foot.

PMID- 15871968
TI  - Early predictors for lower extremity amputation in a diabetic population: results
      of a case-controlled study.
AB  - Lower extremity amputation is devastating to any person and is a very real
      complication for a diabetic. Identifying early risk factors is tantamount to
      saving a limb. This study used the national hospital discharge survey to identify
      2206 control patients and 2098 diabetic patients with a lower extremity
      amputation. These patients were not limited based on gender or race as in
      previous studies. The results show that nephropathy and retinopathy are early
      predictors.

PMID- 15871969
TI  - A comparison of plantar pressure in patients with diabetic foot ulcers using
      different hosiery.
AB  - Abnormally high plantar pressure has been associated with the development of foot
      ulcers in populations with diabetes. Improved foot care includes the use of
      hosiery (socks) as well appropriate footwear. In this study, the Parotec System,
      an in-shoe plantar pressure measurement device, was used to measure the plantar
      pressure of the forefoot of 21 participants. All patients were diagnosed with
      diabetes and were assessed while wearing a combination of either a diabetic
      sock,a dress sock, or no sock and the participant's own shoe or slipper. There
      were no statistically significant differences between combinations of socks and
      footwear.

PMID- 15871970
TI  - Patient compliance: its relevance to the management of a patient with Charcot's
      foot.
AB  - This case report discusses the challenges related to the management of a diabetic
      patient with Charcot's foot and a neuropathic foot ulcer. The patient received
      good coordinated care including foot pressure measurements. The case is an
      example demonstrating that patient compliance is a determinant of treatment
      outcome.

PMID- 15871971
TI  - What can wound fluids tell us about the venous ulcer microenvironment?
AB  - Research into the healing of venous leg ulcers is increasing as they are a common
      problem. The wound fluid bathing an ulcer is thought to reflect the wound
      microenvironment, and the properties of wound fluids have been studied in
      attempts to find ways to promote healing. After a brief summary of normal wound
      healing, this article reviews some of the research that has been carried out on
      venous ulcer wound fluid, with respect to its biochemistry, proteolytic nature,
      growth factor profile, and effects on cell cultures. Some of the problems and
      pitfalls inherent in performing and interpreting wound fluid studies are
      discussed. Finally, a proposal is made for standardizing research on wound fluids
      that would improve comparisons between different studies.

PMID- 15871972
TI  - Optical measurement of tissue oxygen saturation.
AB  - Advances in opto-electronic systems have meant that optical spectroscopy can now
      be used for noninvasive measurements in tissue in patients. A number of
      techniques have evolved over the last 15 years that make use of the
      characteristic differences in the absorption spectrum of deoxygenated and
      oxygenated hemoglobin to measure oxygen saturation. This article summarizes, in
      particular, those techniques that may prove to be applicable to measurements
      relating to lower extremity wounds. A short introduction is given about existing
      electrode methods before describing applications of near infrared and visible
      wavelength spectroscopy to measurements in tissue. The advantages and limitations
      of these methods are discussed. An example of an area where tissue spectroscopy
      is now in routine clinical use for tissue healing viability assessment is
      presented.

PMID- 15871973
TI  - Risk factors for the swollen ankle and their management at low cost: not
      forgetting lymphedema.
AB  - Lymphedema is a common global problem that affects the lower limb. Lymphatics are
      the pathways for the traffic of the immune system as well as the drainage system
      of the skin. Disruption of the normal function of the lymph may lead to limb
      swelling often exacerbated by obesity and immobility. This article presents
      developments in understanding and suggests principles of management with a view
      to promoting debate about this neglected condition.

PMID- 15871974
TI  - Mathematical methods relevant to the study of wound healing.
AB  - Over recent years there has been a growing interest in the application of
      mathematical techniques and methods to improve understanding of clinical
      problems. Mathematical methods permit accurate description and quantification of
      observations and processes. Wound healing is a clinical problem that needs
      support in order to improve management and understanding of the mechanisms that
      may disarrange healing processes. This article attempts to provide an overview of
      currently available methods that have a direct relevance to the management of
      lower extremity wounds. Mathematics can provide valuable assistance and insight
      to clinical understanding, but only if applied correctly. It is hoped that
      examples of good practice will promote the utilization of this versatile tool.

PMID- 15871975
TI  - The role of ultrasound in lower extremity wound management.
AB  - Imaging and hemodynamic information are essential in determining the etiology of
      lower extremity wounds. Ultra- sound offers a noninvasive method of studying
      vessel walls and measuring blood flow, thereby providing reliable diagnostic
      data. This article reviews the role of ultrasound in the management of the lower
      extremity wound.

PMID- 15871976
TI  - Skin grafting of venous ulcers: a review of its current role.
AB  - As a therapeutic option, grafting of venous ulcers has not been very successfully
      received despite the different types of grafting methods. Currently, there are
      only a few controlled randomized trials offering clear guidance to clinicians.
      The development of artificially bioengineered skin constructs has led to a
      renewed interest in wound bed preparation, and preliminary successes suggest that
      the role of skin grafting could be studied in the current context.

PMID- 15871977
TI  - The unilateral swollen lower limb: etiology, investigation, and management.
AB  - The swollen lower limb, a common finding in routine clinical practice, is
      clinically challenging. The cause underlying this problem is often
      multifactorial, and its management may involve different specialties. It is
      important, though difficult, to avoid unnecessary and expensive investigations.
      The aim of this article is to provide an overview of the management of this
      problem by addressing the common causes, methods of assessment, diagnosis, and
      therapeutic options.

PMID- 15871979
TI  - Debridement of chronic wounds: a nursing perspective.

PMID- 15871978
TI  - Contact sensitization in patients with leg ulcers and/or leg eczema: comparison
      between centers.
AB  - Patients with leg ulcers and/or eczema of the legs are at risk of contact
      sensitization. The aim of this retrospective study was to investigate the impact
      of some aspects of practice of leg ulcer treatment and availability of drugs and
      dressings in a university-based wound care center. These data were compared with
      those from the Information Network of Departments of Dermatology (IVDK), where
      patch test reactions of 3529 patients with leg ulcers and/or eczema of the lower
      legs were documented. Data analyses showed frequencies of sensitization for
      single and multiple allergens. The change of treatment modalities may have a
      positive impact on lowering sensitization rates, but the ongoing use of topical
      drugs outside wound care centers may be expected to limit the effects of modern
      wound treatment.

PMID- 15871980
TI  - Towards safer neonatal transfer: the importance of critical incident review.
AB  - BACKGROUND: Critical incidents are common during the inter-hospital transfer of
      sick patients, and infants are an especially vulnerable group. AIMS: To examine
      the effect of critical incident review on the number of adverse events during
      inter-hospital transfer of sick infants. METHODS: Critical incidents over an
      eight year period are reported from a single neonatal transfer service before and
      after major service changes were made. The changes were instigated as part of
      ongoing critical incident reviews. RESULTS: Changes made as a result of critical
      incident review significantly reduced the number of incidents contributed to by
      poor preparation, transport equipment or clinical problems, ambulance delays, and
      ambulance equipment failure. CONCLUSIONS: The continuous process of critical
      incident reporting and review can reduce the number of adverse events during the
      transfer of critically ill infants.

PMID- 15871981
TI  - New Zealand national incidence of bronchiectasis "too high" for a developed
      country.
AB  - AIMS: To prospectively estimate the incidence of bronchiectasis among New Zealand
      (NZ) children, to consider aetiology and severity, and to evaluate regional and
      ethnic variation. METHODOLOGY: NZ paediatricians were surveyed monthly for new
      cases of bronchiectasis during 2001 and 2002 via the NZ paediatric surveillance
      unit (with coverage of >94% of NZ paediatricians). Notified cases had their
      computed tomography scans reviewed and scored for severity. Confirmed cases were
      followed up by postal questionnaire one year after diagnosis. Demographic,
      aetiological, and severity data were collected. RESULTS: Ninety nine
      notifications were received. Sixty five cases were confirmed. An overall
      incidence of 3.7 per 100,000 under 15 year old children per year was estimated.
      Incidence was highest in Pacific children at 17.8 compared with 4.8 in Maori, 1.5
      in NZ European, and 2.4 other per 100,000 per year. Incidence varied
      significantly by region. The median age at diagnosis was 5.2 years; the majority
      had symptoms for more than two years. Eighty three per cent had bilateral
      disease, with a median of three lobes affected, mean FEV1 of 77% predicted, and
      modified Bhalla HRCT score of 18. CONCLUSIONS: The incidence of bronchiectasis is
      high in NZ children, nearly twice the rate for cystic fibrosis and seven times
      that of Finland, the only other country reporting a childhood national rate.
      Incidence varied substantially between ethnicities. Most cases developed disease
      in early childhood and had delayed diagnosis.

PMID- 15871982
TI  - Risk of hypertension with multicystic kidney disease: a systematic review.
AB  - BACKGROUND: Children with multicystic kidney disease (MCKD) are increasingly
      managed conservatively, and are followed up throughout childhood because of the
      risk of hypertension highlighted in some reports. With this risk still poorly
      defined, the strategy and the duration of follow up do not seem to be based on
      evidence. METHODS: Systematic review of the literature for all published cohort
      studies (prospective and retrospective) of children diagnosed to have unilateral
      MCKD and managed conservatively. Exclusion criteria were bilateral MCKD, and
      nephrectomy (not for hypertension) during the follow up period. For children with
      MCKD, the probability of developing hypertension during the follow up period was
      estimated. RESULTS: From 29 reviewed studies, six cases of hypertension developed
      in 1115 eligible children. The mean probability of a child with unilateral MCKD
      developing hypertension was therefore 5.4 per 1000 (95% CI estimated at 1.9 to
      11.7 per 1000). CONCLUSION: Although the risk of hypertension in MCKD is low, the
      results of this study do not allow firm recommendations on the frequency and
      duration of blood pressure measurement follow up for these children. Large
      prospective cohort studies with a very long duration of follow up are needed.

PMID- 15871983
TI  - Risk of long term renal impairment and duration of follow up recommended for
      Henoch-Schonlein purpura with normal or minimal urinary findings: a systematic
      review.
AB  - BACKGROUND: The duration of follow up to assess the risk of long term renal
      impairment in Henoch-Schonlein purpura (HSP) without nephritic or nephrotic
      syndrome or renal failure on diagnosis remains undetermined. AIMS: To undertake a
      systematic review of the literature to assess whether the risk of long term renal
      impairment without renal involvement on diagnosis could be estimated and to
      determine the time period when renal involvement is very unlikely after the
      diagnosis of HSP. METHODS: Search of studies of unselected children with HSP, and
      available information on urinary findings, renal involvement, and long term renal
      function follow up. Studies of selected children with HSP nephropathy at
      diagnosis were excluded. RESULTS: Twelve studies of 1133 children were reviewed.
      The follow up period ranged from 6 weeks to 36 years. Proteinuria and/or
      haematuria, which occurred in 34.2%, of which only one fifth were in association
      with nephritic or nephrotic syndrome, developed in 85% of cases within 4 weeks of
      the diagnosis of HSP, in 91% within 6 weeks, and in 97% within 6 months.
      Permanent renal impairment never developed after normal urinalysis; it occurred
      in 1.6% of those with isolated urinary abnormalities, and in 19.5% of those who
      developed nephritic or nephrotic syndrome. CONCLUSION: No long term renal
      impairment occurred after normal urinalysis. Even if urinalysis is normal at
      presentation, the testing should be continued for six months. There is no need to
      follow up after the first six months those whose urinalysis remains normal.

PMID- 15871984
TI  - Are the risk factors for SIDS different for preterm and term infants?
AB  - BACKGROUND: Mortality from SIDS has declined since the recommendation that
      infants are not placed prone to sleep. SIDS mortality is higher in infants born
      preterm than those born at term. AIM: To determine if risk factors for SIDS are
      any different for preterm and term infants. METHODS: Mortality data over time
      were used to determine whether the reduction in SIDS mortality rates had occurred
      equally in term and preterm infants. Data from two New Zealand studies (a case
      control study and a case-cohort study) were used to determine if any differences
      existed in risk factors for SIDS between term and preterm infants before and
      after the SIDS prevention campaign. RESULTS: SIDS mortality appears to have
      decreased by similar proportions in term and preterm infants. Risk factors for
      SIDS were similar in preterm and term infants, except for parity where there was
      a significant interaction. Increasing parity was a risk factor for SIDS in term
      infants but not preterm infants. CONCLUSION: SIDS rates have decreased at
      comparable rates in term and preterm infants, but preterm birth still remains a
      risk factor for SIDS. The magnitude of the odds ratios associated with modifiable
      risk factors were similar for both groups. There may however be a difference in
      risk associated with parity between term and preterm infants. The messages for
      risk factors for SIDS are applicable to mothers of preterm as well as term
      infants.

PMID- 15871985
TI  - The role of magnetic resonance imaging in the assessment of suspected extrinsic
      tracheobronchial compression due to vascular anomalies.
AB  - AIMS: To evaluate the role of magnetic resonance imaging (MRI) in the assessment
      of children with suspected extrinsic tracheobronchial compression due to vascular
      anomalies. METHODS: Retrospective case note review in a tertiary referral centre.
      Twenty nine children who underwent dynamic laryngotracheobronchoscopy (DLTB) and
      were found to have a clinical suspicion of extrinsic tracheobronchial compression
      were evaluated. All subsequently underwent thoracic MRI within 10 days. The
      findings on endoscopy were compared to those of MRI, and where performed,
      echocardiography, aortography, and surgery. RESULTS: There were 17 males and 12
      females (mean age 5 months, range 28 weeks gestation to 60 months). The most
      common presenting features were stridor and cyanotic episodes. MRI showed
      abnormalities in 21 patients. There were five vascular rings (three double aortic
      arches and two right aortic arches) and 11 cases of innominate artery
      compression. Other vascular anomalies noted included aberrant right subclavian
      artery and aneurysmal left pulmonary artery. Echocardiography was generally found
      to be unhelpful in the diagnosis of extra-cardiac vascular abnormalities.
      Angiography was subsequently conducted in eight children; findings agreed with
      those shown on MRI. Surgery was performed on all five vascular rings, one
      innominate artery compression, and one aneurysmal left pulmonary artery. Surgical
      findings were also compatible with the preoperative MRI. CONCLUSIONS: This study
      shows the successful use of MRI as the initial imaging modality in endoscopically
      suspected extrinsic vascular compression of the upper airway. It enables accurate
      delineation of vascular anomalies and, unlike aortography, is non-invasive and
      does not require the use of contrast media.

PMID- 15871986
TI  - Gene transfer to the rat kidney in vivo and ex vivo using an adenovirus vector:
      factors influencing transgene expression.
AB  - BACKGROUND: The characteristics of adenovirus-mediated gene transfer into the
      kidney are not well examined. We studied the effects of contact time and
      temperature on adenovirus-mediated transgene expression in rat kidneys, using
      catheter-based in vivo gene transfer and a rat renal transplant model ex vivo.
      METHODS: An adenovirus vector containing the luciferase (Ad-Luc) or beta
      galactosidase (Ad-LacZ) gene was introduced in vivo into the kidney via a renal
      artery catheter. Various contact times and temperatures were evaluated. Ex vivo,
      the renal graft was injected with Ad-Luc through the renal artery, chilled for 60
      min and then transplanted. Luciferase expression was evaluated periodically by a
      non-invasive bioimaging system or histology. Cells expressing the LacZ gene were
      identified by immunoelectron microscopy. RESULTS: In in vivo gene transfer,
      successful transgene expression was achieved; however, its efficiency was
      independent of contact time or temperature. In ex vivo gene transfer, transgene
      expression in the renal graft peaked early and gradually decreased. Strong gene
      expression was observed in the recipients' livers. LacZ expression was detected
      in fibroblasts, parietal epithelial cells of Bowman's capsule, mesangial cells,
      podocytes and tubular cells. CONCLUSIONS: This study generated new information
      about in vivo and ex vivo gene transfer into the kidney, which would be useful
      for renal gene therapy.

PMID- 15871987
TI  - Skin to calcaneus distance in the neonate.
AB  - BACKGROUND: Current recommendations for obtaining blood from neonates advise
      avoidance of the midline area of the heel and are based on postmortem studies.
      OBJECTIVE: Because of the potential pain and tissue damage from repeated heel
      pricking in the same area, to investigate using ultrasonography whether the
      distance from skin to calcaneus is less at the midline than at the borders.
      METHODS: One hundred consecutive healthy preterm and 105 consecutive healthy term
      neonates were studied 48-72 hours after delivery. The skin to perichondrium
      distance (SPD) was measured on two occasions by ultrasound at the external,
      midline, and internal areas of the heel. FINDINGS: Mean SPD was 0.2 mm less at
      the midline than at the other sites. The proportion of measurements <3 mm at any
      of the three sites was the same. Depth was <3 mm in less than 3% of the term and
      approximately 20% of the preterm infants. The SPD correlated only with
      gestational age. Of children <33 weeks gestational age, 38% had an SPD <3 mm
      compared with 8% of older preterm infants. The proportions of preterm infants of
      > or = 33 weeks gestation and term infants with an SPD <3 mm were similar (8% v
      3%). INTERPRETATION: With the use of automated lancets of 2.2 mm length or less,
      the whole heel plantar surface is safe for obtaining blood in term and preterm
      infants of > or = 33 weeks gestation. This means that soft tissue damage and pain
      from repeated pricking in the same area can be reduced.

PMID- 15871988
TI  - Neonatal resuscitation 3: manometer use in a model of face mask ventilation.
AB  - BACKGROUND: Adequate ventilation is the key to successful neonatal resuscitation.
      Positive pressure ventilation (PPV) is initiated with manual ventilation devices
      via face masks. These devices may be used with a manometer to measure airway
      pressures delivered. The expiratory tidal volume measured at the mask
      (V(TE(mask))) is a good estimate of the tidal volume delivered during simulated
      neonatal resuscitation. AIM: To assess the effect of viewing a manometer on the
      peak inspiratory pressures used, the volume delivered, and leakage from the face
      mask during PPV with two manual ventilation devices in a model of neonatal
      resuscitation. METHODS: Participants gave PPV to a modified resuscitation
      mannequin using a Laerdal infant resuscitator and a Neopuff infant resuscitator
      at specified pressures ensuring adequate chest wall excursion. Each participant
      gave PPV to the mannequin with each device twice, viewing the manometer on one
      occasion and unable to see the manometer on the other. Data from participants
      were averaged for each device used with the manometer and without the manometer
      separately. RESULTS: A total of 7767 inflations delivered by the 18 participants
      were recorded and analysed. Peak inspiratory pressures delivered were lower with
      the Laerdal device. There were no differences in leakage from the face mask or
      volumes delivered. Whether or not the manometer was visible made no difference to
      any measured variable. CONCLUSIONS: Viewing a manometer during PPV in this model
      of neonatal resuscitation does not affect the airway pressure or tidal volumes
      delivered or the degree of leakage from the face mask.

PMID- 15871989
TI  - Neonatal resuscitation 2: an evaluation of manual ventilation devices and face
      masks.
AB  - BACKGROUND: The key to successful neonatal resuscitation is effective
      ventilation. Little evidence exists to guide clinicians in their choice of manual
      ventilation device or face mask. The expiratory tidal volume measured at the mask
      (V(TE(mask))) is a good estimate of the tidal volume delivered during simulated
      neonatal resuscitation. AIM: To compare the efficacy of (a) the Laerdal infant
      resuscitator and the Neopuff infant resuscitator, used with (b) round and
      anatomically shaped masks in a model of neonatal resuscitation. METHODS: Thirty
      four participants gave positive pressure ventilation to a mannequin at specified
      pressures with each of the four device-mask combinations. Flow, inspiratory tidal
      volume at the face mask (V(TI(mask))), V(TE(mask)), and airway pressure were
      recorded. Leakage from the mask was calculated from V(TI(mask)) and V(TE(mask)).
      RESULTS: A total of 10,780 inflations were recorded and analysed. Peak
      inspiratory pressure targets were achieved equally with the Laerdal and Neopuff
      resuscitators. Positive end expiratory pressure was delivered with the Neopuff
      but not the Laerdal device. Despite similar peak pressures, V(TE(mask)) varied
      widely. Mask leakage was large for each combination of device and mask. There
      were no differences between the masks. CONCLUSION: During face mask ventilation
      of a neonatal resuscitation mannequin, there are large leaks around the face
      mask. Airway pressure is a poor proxy for volume delivered during positive
      pressure ventilation through a mask.

PMID- 15871990
TI  - Neonatal resuscitation 1: a model to measure inspired and expired tidal volumes
      and assess leakage at the face mask.
AB  - BACKGROUND: Neonatal resuscitation is a common and important intervention, and
      adequate ventilation is the key to success. In the delivery room, positive
      pressure ventilation is given with manual ventilation devices using face masks.
      Mannequins are widely used to teach and practise this technique. During both
      simulated and real neonatal resuscitation, chest excursion is used to assess
      tidal volume delivery, and leakage from the mask is not measured. OBJECTIVE: To
      describe a system that allows measurement of mask leakage and estimation of tidal
      volume delivery. METHODS: Respiratory function monitors, a modified resuscitation
      mannequin, and a computer were used to measure leakage from the mask and to
      assess tidal volume delivery in a model of neonatal resuscitation. RESULTS: The
      volume of gas passing through a flow sensor was measured at the face mask. This
      was a good estimate of the tidal volume entering and leaving the lung in this
      model. Gas leakage between the mask and mannequin was also measured. This
      occurred principally during inflation, although gas leakage during deflation was
      seen when the total leakage was large. A volume of gas that distended the mask
      but did not enter the lung was also measured. CONCLUSION: This system can be used
      to assess the effectiveness of positive pressure ventilation given using a face
      mask during simulated neonatal resuscitation. It could be useful for teaching
      neonatal resuscitation and assessing ventilation through a face mask.

PMID- 15871991
TI  - Venepuncture is preferable to heel lance for blood sampling in term neonates.
AB  - BACKGROUND: The analgesic effect of oral sucrose in newborn infants undergoing
      painful procedures is generally accepted. For blood sampling, some studies have
      shown that venepuncture (VP) is less painful than heel lance (HL). OBJECTIVE: To
      determine the least painful and most effective method among blood sampling by VP
      or HL with or without sucrose. DESIGN: Randomised, double blind, placebo
      controlled trial. SUBJECTS: A total of 100 healthy, full term newborn infants
      being screened for inborn errors of metabolism were randomly allocated to one of
      four experimental groups (25 infants in each). Intervention and OUTCOME MEASURE:
      Seven specially trained nurses took turns to carry out blood sampling two minutes
      after administration of oral sucrose or water. Neonatal pain was assessed by the
      neonatal facial coding system (NFCS), as well as by crying. RESULTS: Without
      sucrose, the NFCS score was higher in the HL group than the VP group during blood
      sampling (median 58 v 23, p<0.001). Oral sucrose significantly reduced the score
      of the HL group (58 v 47, p<0.01) and also tended to reduce the score of the VP
      group (23 v 2, p<0.1). However, the HL with sucrose group still had a higher
      score than the VP without sucrose group (47 v 23, p<0.01). Crying and the total
      procedure time showed the same trends as the NFCS score. CONCLUSIONS: VP is less
      painful and more effective than HL for blood sampling in newborn infants.
      Although oral sucrose may have an additive analgesic effect, it is not
      necessarily required if VP is used for blood sampling.

PMID- 15871992
TI  - The importance of irradiance and area in neonatal phototherapy.
AB  - BACKGROUND: Despite a long period of development, there are still considerable
      variations in the spectral output, the levels of irradiance, and irradiated area
      provided by commercial phototherapy systems. These variations depend on the types
      and output of the lamps used to produce the phototherapy, along with the design
      of the systems, and principally on whether the phototherapy is provided from
      overhead or underneath. OBJECTIVE: To see whether commercially available
      phototherapy systems produce sufficient irradiance over the surface area of the
      neonate. METHODS: Surface plots of the output irradiance were made on a number of
      systems and used to calculate the effective irradiance on the surface of a
      premature or term baby, using mapped outlines. RESULTS: A 10-fold difference in
      peak central irradiances was found between the systems tested, with a fourfold to
      fivefold difference in effective irradiance to the baby surfaces. Although work
      published over 20 years ago showed that levels of irradiance should reach 2
      mW/cm2 to achieve optimal effectiveness, some of the commercial systems tested do
      not appear to achieve this level. CONCLUSION: Purchasers of neonatal phototherapy
      systems need to take into account whether the systems will produce sufficient
      irradiance over the area to ensure maximal effect, to keep the treatment time to
      a minimum.

PMID- 15871993
TI  - Are ethnic differences in lung function explained by chest size?
AB  - BACKGROUND: Ethnic differences in lung function (LF) are recognised in adults and
      children. Most prediction equations for LF are derived from whites, so non-whites
      are at risk of erroneous assessment. It was hypothesised that differences in
      chest dimensions would explain differences in LF between Asian (Indian) and white
      schoolchildren. AIMS: To quantify the impact of chest dimensions on LF, which
      would inform our understanding of ethnic differences that have implications for
      health care. METHODS: Children aged 6-11 were studied in school. A questionnaire
      provided information on ethnicity and respiratory health. Spirometry was used to
      record FVC, FEV1, FEF25-75, and PEF. Weight, height, sitting height, and chest
      dimensions (chest height, circumference, antero-posterior and transverse
      diameters) were measured. RESULTS: Data were obtained from 294 healthy children.
      Standing height was the most important predictor of LF. Ethnicity was an
      independent predictor for all LF measures except PEF, where the effect was
      marginal. FVC in whites was 13.4% bigger than in Asians of the same height, and
      the FEV1 was 10.6% greater in whites. The influence of chest dimensions on lung
      function was trivial. Body mass index was smaller in Asians but did not explain
      differences in LF. CONCLUSIONS: Differences in chest dimensions did not explain
      the substantial effect of ethnicity on LF. Mechanisms whereby ethnicity exerts
      its influence may include differences in inspiratory muscle strength or lung
      compliance but remain speculative. Nevertheless it remains imperative that ethnic
      differences are recognised when interpreting LF tests.

PMID- 15871994
TI  - Impact of EGFR expression on colorectal cancer patient prognosis and survival: a
      response.

PMID- 15871996
TI  - How much did cold shock and swimming failure contribute to drowning deaths in the
      fishing industry in British Columbia 1976-2002?
AB  - BACKGROUND: The Workers' Compensation Board of British Columbia requested a
      retrospective analysis of all fishermen's deaths from immersion in water in
      British Columbia. AIMS: To identify the underlying cause of drowning and make
      recommendations to improve safety in the fishing industry. METHOD: Eighty-nine
      inshore and offshore fishing accidents were analysed. Where possible, deaths were
      classified into the four stages of cold-water immersion: cold shock, swimming
      failure, hypothermia and post-rescue collapse. Other factors that led up to the
      drowning were also identified. RESULTS: One hundred and thirty fishermen died
      from immersion between 1976 and 2002. One hundred and twenty-eight drownings were
      certified by the coroner as drowning or drowning/hypothermia and two were
      certified as cardiac event after immersion. The underlying causes of drownings
      were reclassified as: cold shock (5.4%), swimming failure (5.4%), hypothermia
      (5.4%), post-rescue collapse (0.8%), cardiac event (0.8%) and drowning/other
      (10%). In the remaining 72.2% of deaths, there was insufficient information to
      determine an underlying cause. All deaths occurred in water below 17.5 degrees C
      but 95% were in water less than 15 degrees C. CONCLUSIONS: Immersion in water
      below 15 degrees C is dangerous and this should be emphasized on marine survival
      courses. Accident investigators, coroners and pathologists need a common
      checklist to record vital data. A recommended format is included as Supplementary
      data available at Occupational Medicine Online. Fishermen should be educated
      about the dangers of sudden, unexpected immersion in cold water. Consideration
      should be given to making marine survival courses mandatory for fishermen.

PMID- 15871997
TI  - Prognostic determinants for chronic hepatitis B in Asians: therapeutic
      implications.
AB  - BACKGROUND: Identifying risk factors for the development of complications of
      chronic hepatitis B (CHB) is important for setting up treatment criteria. AIM: To
      determine risk factors for the development of complications in Asian CHB
      patients. PATIENTS AND METHODS: A total of 3233 Chinese CHB patients (mean follow
      up 46.8 months) were monitored for liver biochemistry, viral serology, hepatitis
      B virus (HBV) DNA levels, acute exacerbation, hepatitis B e antigen (HBeAg)
      seroconversion, and development of cirrhotic complications and hepatocellular
      carcinoma. RESULTS: Median age for HBeAg seroconversion and development of
      complications was 35 years and 57.2 years, respectively. Patients with alanine
      aminotransferase (ALT) levels of 0.5-1 times the upper limit of normal (ULN) and
      1-2x ULN had an increased risk for the development of complications compared with
      patients with ALT levels <0.5x ULN (p<0.0001 for both). HBeAg/antibody to
      hepatitis B e antigen status, and number of episodes, duration, and peak ALT
      levels of acute exacerbations were not associated with an increased risk of
      complications. In patients with complications, 43.6% had HBV DNA levels less than
      1.42x10(5) copies/ml. Male sex, stigmata of chronic liver disease, old age, low
      albumin, and high alpha fetoprotein levels on presentation were independently
      associated with increased cumulative risk of complications. Male sex, presence of
      hepatitis symptoms, old age, low albumin level, and presence of complications on
      presentation were independently associated with shorter survival. CONCLUSION:
      Prolonged low level viraemia causing insidious and continual liver damage, as
      reflected by ALT levels of 0.5-2x ULN, is the most likely pathway for the
      development of complications in Asian CHB patients.

PMID- 15871998
TI  - CREB/PKA sensitive signalling pathways activate and maintain expression levels of
      the hepatitis B virus pre-S2/S promoter.
AB  - BACKGROUND AND AIMS: CREB (cAMP response element binding protein) transcription
      factors are key regulators of homeostatic functions in the liver, and CRE binding
      is increased in hepatic inflammation. During chronic hepatitis B virus (HBV)
      infection, mutations or deletions in the pre-S region are frequently observed.
      These mutations can affect the pre-S2/S promoter controlling HBV envelope protein
      expression (hepatitis B surface antigen (HBsAg)) and have been associated with
      worsened clinical outcome. We aimed to test if CREB activation impacts on HBsAg
      expression. METHODS: The effect of the CREB inducer protein kinase A (PKA) was
      tested by coexpression with HBV wild-type vector in vitro. Luciferase reporter
      gene constructs were cloned to identify novel regulatory regions for the HBV pre
      S2/S promoter. Electrophoretic mobility shift assay (EMSA) gelshift and
      supershift experiments were conducted to confirm DNA transcription factor
      binding. RESULTS: Coexpression of HBV and PKA resulted in HBV-S mRNA induction
      and enhanced small envelope protein expression. We identified a CREB binding
      motif in the transcribed part of the pre-S2 region, contributing to basal S
      promoter activity via binding of activating transcription factor 2 (ATF2). A
      second CREB motif closely linked to the S-ATG showed a similar binding pattern
      involving ATF2 and CREB1, without appearing essential for basal promoter
      activity. Moreover, a sequence in the pre-S2 region is responsible for further
      transcriptional induction via CREB activators such as PKA and forskolin. EMSA
      experiments indicate that CREB1 and ATF4 are involved in complex formation
      conferring PKA dependent promoter activation. CONCLUSIONS: Our data suggest a
      novel mechanism by which HBV may utilise CREB/PKA signal transduction pathways of
      hepatocytes to enhance its HBsAg expression during homeostasis and hepatic
      inflammation.

PMID- 15871999
TI  - Incomplete screening flexible sigmoidoscopy associated with female sex, age, and
      increased risk of colorectal cancer.
AB  - BACKGROUND: Several previous studies have found that females and older
      individuals are at greater risk of having incomplete flexible sigmoidoscopy.
      However, no prior study has reported the subsequent risk of colorectal cancer
      (CRC) following incomplete sigmoidoscopy. METHODS: Using data from 55 791
      individuals screened as part of the Colon Cancer Prevention (CoCaP) programme of
      Kaiser Permanente of Northern California, we evaluated the likelihood of having
      an inadequate (<40 cm) examination by age and sex, and estimated the risk of
      distal CRC according to depth of sigmoidoscope insertion at the baseline
      screening examination. Multivariate estimation of risks was performed using
      Poisson regression. RESULTS: Older individuals were at a much greater risk of
      having an inadequate examination (relative risk (RR) for age 80+ years compared
      with 50-59 years 2.6 (95% confidence interval (CI) 2.3-3.0)), as were females (RR
      2.3 (95% CI 2.2-2.5)); these associations were attenuated but remained strong if
      Poisson models were further adjusted for examination limitations (pain, stool,
      and angulation). There was an approximate threefold increase in the risk of
      distal CRC if the baseline sigmoidoscopy did not reach a depth of at least 40 cm;
      a smaller increase in risk was observed for examinations that reached 40-59 cm.
      CONCLUSIONS: Older individuals and women are at an increased risk of having
      inadequate sigmoidoscopy. Because inadequate sigmoidoscopy results in an
      increased risk of subsequent CRC, physicians should consider steps to maximise
      the depth of insertion of the sigmoidoscope or, failing this, should consider an
      alternative screening test.

PMID- 15872000
TI  - Helicobacter pylori eradication induces marked increase in H+/K+-adenosine
      triphosphatase expression without altering parietal cell number in human gastric
      mucosa.
AB  - BACKGROUND AND AIMS: Gastric acid secretion is downregulated by Helicobacter
      pylori infection and upregulated after its eradication, but the mechanisms are
      still unclear. We examined the effects of H pylori eradication on the number of
      parietal cells and on expression of molecules functioning in acid secretion in
      the human gastric mucosa. METHODS: We enrolled 111 consecutive men with chronic
      gastritis induced by H pylori. Biopsy specimens were endoscopically obtained
      before and 12 weeks after successful eradication of H pylori and parietal cell
      numbers were counted. mRNA expression levels of H+/K+-adenosine triphosphatase
      (H+/K+-ATPase), anion exchanger 2, M3 muscarinic receptor, intrinsic factor, and
      interleukin 1beta were determined with a real time reverse transcriptase
      polymerase chain reaction method. The severity of gastric atrophy was evaluated
      using the serum pepsinogen I/II ratio. RESULTS: No significant difference was
      observed in parietal cell numbers before and after H pylori eradication. Median
      mRNA expression levels of H+/K+-ATPase in the gastric mucosa increased 250-fold
      after H pylori eradication accompanied by attenuation of interleukin 1beta. A
      large increase in H+/K+-ATPase expression was observed even in patients with
      severe atrophic gastritis. In contrast, fold increases in mRNA expression levels,
      including intrinsic factor, anion exchanger 2, and M3 muscarinic receptor, after
      eradication therapy, were limited to 1.4, 2.3, and 2.5 times, respectively.
      CONCLUSIONS: In the absence of alteration of parietal cell number, gastric H+/K+
      ATPase mRNA expression was markedly restored after successful H pylori
      eradication, suggesting a central role for the restoration of H+/K+-ATPase
      expression in gastric acid secretion recovery after H pylori eradication.

PMID- 15872001
TI  - Process evaluation of a store-based environmental obesity intervention on two
      American Indian Reservations.
AB  - Obesity and other diet-related chronic diseases are widespread in American Indian
      communities. Inadequate access to healthy food on many reservations has led to a
      high-fat, high-sugar diet. The purpose of this paper is to report on the results
      of the process evaluation of a food store-based program to improve diet on two
      American Indian reservations. Process data were collected from 11 intervention
      stores to document the implementation of the Apache Healthy Stores (AHS) program.
      Process evaluation instruments recorded the stocking of promoted foods, presence
      of in-store communication materials, implementation of and participation in the
      cooking demonstrations and taste tests, and the transmission of mass-media
      messages. At the store level, the program was implemented with a high level of
      dose and reach, and a moderate to high level of fidelity. At the community level,
      the AHS program was implemented with a moderate degree of fidelity and dose. At
      the individual level, the cooking demonstrations and taste tests reached a large
      number of community members with a high dose. Implementing the AHS program on
      multiple levels (store, community, individual) was challenging, and differed
      between levels. Overall, improvements were seen from start to finish as program
      staff monitored, documented and responded to barriers to implementation. Process
      data will be tied to outcomes and will be useful for the planning of future store
      based programs.

PMID- 15872002
TI  - The boundary cap: a source of neural crest stem cells that generate multiple
      sensory neuron subtypes.
AB  - The boundary cap (BC) is a transient neural crest-derived group of cells located
      at the dorsal root entry zone (DREZ) that have been shown to differentiate into
      sensory neurons and glia in vivo. We find that when placed in culture, BC cells
      self-renew, show multipotency in clonal cultures and express neural crest stem
      cell (NCSCs) markers. Unlike sciatic nerve NCSCs, the BC-NCSC (bNCSCs) generates
      sensory neurons upon differentiation. The bNCSCs constitute a common source of
      cells for functionally diverse types of neurons, as a single bNCSC can give rise
      to several types of nociceptive and thermoreceptive sensory neurons. Our data
      suggests that BC cells comprise a source of multipotent sensory specified stem
      cells that persist throughout embryogenesis.

PMID- 15872004
TI  - Matching catalytic activity to developmental function: tolloid-related processes
      Sog in order to help specify the posterior crossvein in the Drosophila wing.
AB  - The Drosophila tolloid (tld) and tolloid related (tlr) gene products belong to a
      family of developmentally important proteases that includes Bone Morphogenetic
      Protein 1 (Bmp1). Tld is required early in Drosophila development for proper
      patterning of dorsal embryonic structures, whereas Tlr is required later during
      larval and pupal stages of development. The major function of Tld is to augment
      the activity of Decapentaplegic (Dpp) and Screw (Scw), two members of the Bmp
      subgroup of the Tgf beta superfamily, by cleaving the Bmp inhibitor Short
      gastrulation (Sog). In this study, we provide evidence that Tlr also contributes
      to Sog processing. Tlr cleaves Sog in vitro in a Bmp-dependent manner at the same
      three major sites as does Tld. However, Tlr shows different site selection
      preferences and cleaves Sog with slower kinetics. To test whether these
      differences are important in vivo, we investigated the role of Tlr and Tld during
      development of the posterior crossvein (PCV) in the pupal wing. We show that tlr
      mutants lack the PCV as a result of too little Bmp signaling. This is probably
      caused by excess Sog activity, as the phenotype can be suppressed by lowering Sog
      levels. However, Tld cannot substitute for Tlr in the PCV; in fact, misexpressed
      Tld can cause loss of the PCV. Reducing levels of Sog can also cause loss of the
      PCV, indicating that Sog has not only an inhibitory but also a positive effect on
      signaling in the PCV. We propose that the specific catalytic properties of Tlr
      and Tld have evolved to achieve the proper balance between the inhibitory and
      positive activities of Sog in the PCV and early embryo, respectively. We further
      suggest that, as in the embryo, the positive effect of Sog upon Bmp signaling
      probably stems from its role in a ligand transport process.

PMID- 15872003
TI  - Shifting boundaries of retinoic acid activity control hindbrain segmental gene
      expression.
AB  - Retinoic acid (RA) generated by Raldh2 in paraxial mesoderm is required for
      specification of the posterior hindbrain, including restriction of Hoxb1
      expression to presumptive rhombomere 4 (r4). Hoxb1 expression requires 3' and 5'
      RA response elements for widespread induction up to r4 and for r3/r5 repression,
      but RA has previously been detected only from r5-r8, and vHnf1 is required for
      repression of Hoxb1 posterior to r4 in zebrafish. We demonstrate in mouse embryos
      that an RA signal initially travels from the paraxial mesoderm to r3, forming a
      boundary next to the r2 expression domain of Cyp26a1 (which encodes an RA
      degrading enzyme). After Hoxb1 induction, the RA boundary quickly shifts to
      r4/r5, coincident with induction of Cyp26c1 in r4. A functional role for Cyp26c1
      in RA degradation was established through examination of RA-treated embryos.
      Analysis of Raldh2-/- and vHnf1-/- embryos supports a direct role for RA in Hoxb1
      induction up to r4 and repression in r3/r5, as well as an indirect role for RA in
      Hoxb1 repression posterior to r4 via RA induction of vHnf1 up to the r4/r5
      boundary. Our findings suggest that Raldh2 and Cyp26 generate shifting boundaries
      of RA activity, such that r3-r4 receives a short pulse of RA and r5-r8 receives a
      long pulse of RA. These two pulses of RA activity function to establish
      expression of Hoxb1 and vHnf1 on opposite sides of the r4/r5 boundary.

PMID- 15872005
TI  - Identification of Pax2-regulated genes by expression profiling of the mid
      hindbrain organizer region.
AB  - The paired domain transcription factor Pax2 is required for the formation of the
      isthmic organizer (IsO) at the midbrain-hindbrain boundary, where it initiates
      expression of the IsO signal Fgf8. To gain further insight into the role of Pax2
      in mid-hindbrain patterning, we searched for novel Pax2-regulated genes by cDNA
      microarray analysis of FACS-sorted GFP+ mid-hindbrain cells from wild-type and
      Pax2-/- embryos carrying a Pax2(GFP) BAC transgene. Here, we report the
      identification of five genes that depend on Pax2 function for their expression in
      the mid-hindbrain boundary region. These genes code for the transcription factors
      En2 and Brn1 (Pou3f3), the intracellular signaling modifiers Sef and Tapp1, and
      the non-coding RNA Ncrms. The Brn1 gene was further identified as a direct target
      of Pax2, as two functional Pax2-binding sites in the promoter and in an upstream
      regulatory element of Brn1 were essential for lacZ transgene expression at the
      mid-hindbrain boundary. Moreover, ectopic expression of a dominant-negative Brn1
      protein in chick embryos implicated Brn1 in Fgf8 gene regulation. Together, these
      data defined novel functions of Pax2 in the establishment of distinct
      transcriptional programs and in the control of intracellular signaling during mid
      hindbrain development.

PMID- 15872006
TI  - Rabbit retinal ganglion cells express functional alpha7 nicotinic acetylcholine
      receptors.
AB  - It is well known that cholinergic agents affect ganglion cell (GC) firing rates
      and light responses in the retinas of many species, but the specific receptor
      subtypes involved in mediating these effects have been only partially
      characterized. We sought to determine whether functional alpha(7) nicotinic
      acetylcholine receptors (nAChRs) contribute to the responses of specific retinal
      GC classes in rabbit retina. We used electrophysiology, pharmacology,
      immunohistochemistry, and reverse transcriptase-polymerase chain reaction to
      determine the pharmacological properties and expression of nAChR subtypes by
      specific rabbit retinal GC classes. Choline was used as an alpha(7) nAChR
      agonist. Methyllycaconitine (MLA) was used as a competitive alpha(7) nAChR
      antagonist. The application of choline before synaptic blockade resulted in
      changes in retinal GC activity, including increases or decreases in maintained
      firing and/or enhancement or suppression of light responses. Many physiologically
      identified GC types, including sustained off, sustained on, transient off, and
      transient on cells, demonstrated responses to choline application while under
      synaptic blockade. The choline-induced responses could be blocked with MLA,
      confirming alpha(7) nAChR activation. Individual choline-responsive GCs displayed
      mRNA transcripts consistent with the expression of functional alpha(7) nAChRs.
      Other GCs demonstrated physiological responses and mRNA expression consistent
      with the expression of both alpha(7) and non-alpha(7) nAChRs. Thus mRNA is
      present for multiple nAChR subunits in whole retina extracts, and functional
      alpha(7) nAChRs are capable of modulating the responses of GCs in adult rabbit
      retina. We also demonstrate through physiological responses that subsets of GCs
      express more than one nAChR subtype.

PMID- 15872007
TI  - STa and cGMP stimulate CFTR translocation to the surface of villus enterocytes in
      rat jejunum and is regulated by protein kinase G.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is critical to
      cAMP- and cGMP-activated intestinal anion secretion and the pathogenesis of
      secretory diarrhea. Enterotoxins released by Vibrio cholerae (cholera toxin) and
      Escherichia coli (heat stable enterotoxin, or STa) activate intracellular cAMP
      and cGMP and signal CFTR on the apical plasma membrane of small intestinal
      enterocytes to elicit chloride and fluid secretion. cAMP activates PKA, whereas
      cGMP signals a cGMP-dependent protein kinase (cGKII) to phosphorylate CFTR in the
      intestine. In the jejunum, cAMP also regulates CFTR and fluid secretion by
      insertion of CFTR from subapical vesicles to the surface of enterocytes. It is
      unknown whether cGMP signaling or phosphorylation regulates the insertion of CFTR
      associated vesicles from the cytoplasm to the surface of enterocytes. We used
      STa, cell-permeant cGMP, and cAMP agonists in conjunction with PKG and PKA
      inhibitors, respectively, in rat jejunum to examine whether 1) cGMP and cGK II
      regulate the translocation of CFTR to the apical membrane and its relevance to
      fluid secretion, and 2) PKA regulates cAMP-dependent translocation of CFTR
      because this intestinal segment is a primary target for toxigenic diarrhea. STa
      and cGMP induced a greater than fourfold increase in surface CFTR in enterocytes
      in association with fluid secretion that was inhibited by PKG inhibitors. cAMP
      agonists induced a translocation of CFTR to the cell surface of enterocytes that
      was prevented by PKA inhibitors. We conclude that cAMP and cGMP-dependent
      phosphorylation regulates fluid secretion and CFTR trafficking to the surface of
      enterocytes in rat jejunum.

PMID- 15872008
TI  - Degradation of oxidative stress-induced denatured albumin in rat liver
      endothelial cells.
AB  - We previously identified conformationally denatured albumin (D2 and D3 albumin)
      in rats with endotoxicosis (Bito R, Shikano T, and Kawabata H. Biochim Biophys
      Acta 1646: 100-111, 2003). In the present study, we attempted first to confirm
      whether the denatured albumins generally increase in conditions of oxidative
      stress and second to characterize the degradative process of the denatured
      albumin using primary cultured rat liver endothelial cells. We used five models
      of oxidative stress, including endotoxicosis, ischemic heart disease, diabetes,
      acute inflammation, and aging, and found that serum concentrations of D3 albumin
      correlate with the serum levels of thiobarbituric acid-reactive substance (R =
      0.87), whereas the concentrations of D2 albumin are 0.52. Ligand blot analysis
      showed that the D3 albumin binds to gp18 and gp30, which are known endothelial
      scavenger receptors for chemically denatured albumin. Primary cultured rat liver
      endothelial cells degraded the FITC-D3 albumin, and the degradation rate
      decreased to approximately 60% of control levels in response to anti-gp18 and
      anti-gp30 antibodies, respectively. An equimolar mixture of these antibodies
      produced an additive inhibitory effect on both uptake and degradation, resulting
      in levels approximately 20% those of the control. Furthermore, filipin and
      digitonin, inhibitors of the caveolae-related endocytic pathway, reduced the FITC
      D3 albumin uptake and degradation to <20%. Laser-scanning confocal microscopic
      observation supported these data regarding the uptake and degradation of D3
      albumin. These results indicate that conformationally denatured D3 albumin occurs
      generally under oxidative stress and is degraded primarily via gp18- and gp30
      mediated and caveolae-related endocytosis in liver endothelial cells.

PMID- 15872009
TI  - Mechanical stimulation prevents osteocyte apoptosis: requirement of integrins,
      Src kinases, and ERKs.
AB  - Osteocytes, former osteoblasts entombed in the bone matrix, form an extensive
      cell communication network that is thought to detect microdamage and mechanical
      strains and to transmit signals leading to repair and compensatory bone
      augmentation or reduction. Bone active hormones and drugs control the integrity
      of this network by regulating osteocyte apoptosis, which might be a determinant
      of bone strength. Herein we demonstrate that mechanical stimulation by stretching
      activates the ERKs, which in turn are responsible for the attenuation of
      osteocyte apoptosis. The effect of osteocyte stretching is transmitted by
      integrins and cytoskeletal and catalytic molecules, such as Src kinases. Stretch
      induced antiapoptosis also requires nuclear translocation of ERKs and new gene
      transcription. The evidence linking mechanical stimulation, activation of an
      integrin/cytoskeleton/Src/ERK signaling pathway, and osteocyte survival provides
      a mechanistic basis for the profound role of mechanical forces, or lack thereof,
      on skeletal health and disease.

PMID- 15872010
TI  - Modeling error and stability of endothelial cytoskeletal membrane parameters
      based on modeling transendothelial impedance as resistor and capacitor in series.
AB  - Transendothelial impedance across an endothelial monolayer grown on a
      microelectrode has previously been modeled as a repeating pattern of disks in
      which the electrical circuit consists of a resistor and capacitor in series.
      Although this numerical model breaks down barrier function into measurements of
      cell-cell adhesion, cell-matrix adhesion, and membrane capacitance, such solution
      parameters can be inaccurate without understanding model stability and error. In
      this study, we have evaluated modeling stability and error by using a chi(2)
      evaluation and Levenberg-Marquardt nonlinear least-squares (LM-NLS) method of the
      real and/or imaginary data in which the experimental measurement is compared with
      the calculated measurement derived by the model. Modeling stability and error
      were dependent on current frequency and the type of experimental data modeled.
      Solution parameters of cell-matrix adhesion were most susceptible to modeling
      instability. Furthermore, the LM-NLS method displayed frequency-dependent
      instability of the solution parameters, regardless of whether the real or
      imaginary data were analyzed. However, the LM-NLS method identified stable and
      reproducible solution parameters between all types of experimental data when a
      defined frequency spectrum of the entire data set was selected on the basis of a
      criterion of minimizing error. The frequency bandwidth that produced stable
      solution parameters varied greatly among different data types. Thus a numerical
      model based on characterizing transendothelial impedance as a resistor and
      capacitor in series and as a repeating pattern of disks is not sufficient to
      characterize the entire frequency spectrum of experimental transendothelial
      impedance.

PMID- 15872011
TI  - Polyamine depletion induces nucleophosmin modulating stability and
      transcriptional activity of p53 in intestinal epithelial cells.
AB  - Our previous studies have shown that polyamines are required for normal
      intestinal mucosal growth and that decreased levels of polyamines inhibit
      intestinal epithelial cell (IEC) proliferation by stabilizing p53 and other
      growth-inhibiting proteins. Nucleophosmin (NPM) is a multifunctional protein that
      recently has been shown to regulate p53 activity. In the present study, we sought
      to determine whether polyamine depletion increases NPM modulating the stability
      and transcriptional activity of p53 in a normal IEC-6 intestinal epithelial cell
      line. Depletion of cellular polyamines by alpha-difluoromethylornithine, the
      specific inhibitor of polyamine biosynthesis, stimulated expression of the NPM
      gene and induced nuclear translocation of NPM protein. Polyamine depletion
      stimulated NPM expression primarily by increasing NPM gene transcription and its
      mRNA stability, and it induced NPM nuclear translocation through activation of
      phosphorylation of mitogen-activated protein kinase kinase. Increased NPM
      interacted with p53 and formed a NPM/p53 complex in polyamine-deficient cells.
      Inhibition of NPM expression by small interfering RNA targeting NPM (siNPM) not
      only destabilized p53 as indicated by a decrease in its protein half-life but
      also prevented the increased p53-dependent transactivation as shown by
      suppression of the p21 promoter activity. Decreased expression of NPM by siNPM
      also promoted cell growth in polyamine-deficient cells. These results indicate
      that 1) polyamine depletion increases expression of the NPM gene and enhances NPM
      nuclear translocation and 2) increased NPM interacts with and stabilizes p53,
      leading to inhibition of IEC-6 cell proliferation.

PMID- 15872012
TI  - Do rat cardiac myocytes release ATP on contraction?
AB  - ATP is released by numerous cell types in response to mechanical strain. It then
      acts as a paracrine or autocrine signaling molecule, inducing a variety of
      biological responses. In this work, we addressed the question whether mechanical
      force acting on the membranes of contracting cardiomyocytes during periodic
      longitudinal shortening can stimulate the release of ATP. Electrically stimulated
      isolated adult rat cardiomyocytes as well as spontaneously contracting mouse
      cardiomyocytes derived from embryonic stem (ES) cells were assayed for ATP
      release with the use of luciferase and a sensitive charge-coupled device camera.
      Sensitivity of soluble luciferase in the supernatant of cardiomyocytes was 100 nM
      ATP, which is approximately 10-fold below the EC(50) values for most purinergic
      receptors expressed in the heart (1.5-20 microM). Light intensities were not
      different between resting or contracting adult rat cardiomyocytes. Similar
      results were obtained with ES-cell-derived contracting mouse cardiomyocytes. ATP
      release was measurable only from obviously damaged or permeabilized cells. To
      increase selectivity and sensitivity of ATP detection we have targeted a
      recombinant luciferase to the sarcolemmal membrane using a wheat germ agglutinin
      IgG linker. Contraction of labeled adult rat cardiomyocytes was not associated
      with measurable bioluminescence. However, when human umbilical vein endothelial
      cells were targeted with membrane-bound luciferase, shear stress-induced ATP
      release could be clearly detected, demonstrating the sensitivity of the detection
      method. In the present study, we did not detect ATP release from contracting
      cardiomyocytes on the single cell level, despite adequate sensitivity of the
      detection system. Thus deformation of the contracting cardiomyocyte is not a key
      stimulus for the release of cellular ATP.

PMID- 15872013
TI  - Syntaxin 1A has a specific binding site in the H3 domain that is critical for
      targeting of H+-ATPase to apical membrane of renal epithelial cells.
AB  - H(+) transport in the collecting duct is regulated by exocytic insertion of H(+)
      ATPase-laden vesicles into the apical membrane. The soluble N-ethylmaleimide
      sensitive fusion protein attachment protein (SNAP) receptor (SNARE) proteins are
      critical for exocytosis. Syntaxin 1A contains three main domains, SNARE N, H3,
      and carboxy-terminal transmembrane domain. Several syntaxin isoforms form SNARE
      fusion complexes through the H3 domain; only syntaxin 1A, through its H3 domain,
      also binds H(+)-ATPase. This raised the possibility that there are separate
      binding sites within the H3 domain of syntaxin 1A for H(+)-ATPase and for SNARE
      proteins. A series of truncations in the H3 domain of syntaxin 1A were made and
      expressed as glutathione S-transferase (GST) fusion proteins. We determined the
      amount of H(+)-ATPase and SNARE proteins in rat kidney homogenate that complexed
      with GST-syntaxin molecules. Full-length syntaxin isoforms and syntaxin-1ADeltaC
      [amino acids (aa) 1-264] formed complexes with H(+)-ATPase and SNAP23 and vesicle
      associated membrane polypeptide (VAMP). A cassette within the H3 portion was
      found that bound H(+)-ATPase (aa 235-264) and another that bound SNAP23 and VAMP
      (aa 190-234) to an equivalent degree as full-length syntaxin. However, the aa 235
      264 cassette alone without the SNARE N (aa 1-160) does not bind but requires
      ligation to the SNARE N to bind H(+)-ATPase. When this chimerical construct was
      transected into inner medullary collecting duct cells it inhibited intracellular
      pH recovery, an index of H(+)-ATPase mediated secretion. We conclude that within
      the H3 domain of syntaxin 1A is a unique cassette that participates in the
      binding of the H(+)-ATPase to the apical membrane and confers specificity of
      syntaxin 1A in the process of H(+)-ATPase exocytosis.

PMID- 15872014
TI  - Postoperative alteration of cerebral glucose metabolism in mesial temporal lobe
      epilepsy.
AB  - To investigate postoperative changes in the cerebral glucose metabolism of
      patients with mesial temporal lobe epilepsy (MTLE), statistical parametric
      mapping (SPM) analysis was performed on pre- and postoperative (18)F
      fluorodeoxyglucose PET (FDG-PET) images. We included 28 patients with MTLE who
      had undergone surgery and had been seizure-free postoperatively (16 had left MTLE
      and 12 right MTLE). All patients showed hippocampal sclerosis by pathology or
      brain MRI. FDG-PET images of the 12 right temporal lobe epilepsy patients were
      reversed to lateralize the epileptogenic zone to the left side in all patients.
      Application of the paired t-test in SPM to pre- and postoperative FDG-PETs showed
      that postoperative glucose metabolism decreased in the caudate nucleus, the
      pulvinar of the thalamus, fusiform gyrus, lingual gyrus and the posterior region
      of the insular cortex in the hemisphere ipsilateral to resection, whereas
      postoperative glucose metabolism increased in the anterior region of the insular
      cortex, temporal stem white matter, midbrain, inferior precentral gyrus, anterior
      cingulate gyrus and supramarginal gyrus in the hemisphere ipsilateral to
      resection. No significant postsurgical changes in cerebral glucose metabolism
      occurred in the contralateral hemisphere. Subtraction between pre- and
      postoperative FDG-PET images in individual patients produced similar findings to
      the SPM results, and additionally showed that postoperative glucose metabolism
      increased in the anterior thalamus in 12/28 patients (42.8%). SISCOM (subtraction
      ictal-interictal SPECT co-registered to MRI) performed in 17 patients showed
      ictal hyperperfusion in the ipsilateral temporal lobe, including the temporal
      stem white matter, midbrain, insular cortex and cingulate gyrus, bilateral basal
      ganglia and thalami, and multiple small regions in the frontoparietal lobes
      during seizures. This study suggests that brain regions showing a postoperative
      increase in glucose metabolism appear to represent the propagation pathways of
      ictal and interictal epileptic discharges in MTLE, whereas the postoperative
      decrease in glucose metabolism may be related to a permanent loss of afferents
      from resected anterior-mesial temporal structures.

PMID- 15872015
TI  - Vertical nystagmus: clinical facts and hypotheses.
AB  - The pathophysiology of spontaneous upbeat (UBN) and downbeat (DBN) nystagmus is
      reviewed in the light of several instructive clinical findings and experimental
      data. UBN due to pontine lesions could result from damage to the ventral
      tegmental tract (VTT), originating in the superior vestibular nucleus (SVN),
      coursing through the ventral pons and transmitting excitatory upward vestibular
      signals to the third nerve nucleus. A VTT lesion probably leads to relative
      hypoactivity of the drive to the motoneurons of the elevator muscles with,
      consequently, an imbalance between the downward and upward systems, resulting in
      a downward slow phase. The results observed in internuclear ophthalmoplegia
      suggest that the medial longitudinal fasciculus (MLF) is involved in the
      transmission of both upward and downward vestibular signals. Since no clinical
      cases of DBN due to focal brainstem damage have been reported, it may be assumed
      that the transmission of downward vestibular signals depends only upon the MLF,
      whereas that of upward vestibular signals involves both the MLF and the VTT. The
      main focal lesions resulting in DBN affect the cerebellar flocculus and/or
      paraflocculus. Apparently, this structure tonically inhibits the SVN and its
      excitatory efferent tract (i.e. the VTT) but not the downward vestibular system.
      Therefore, a floccular lesion could result in a disinhibition of the SVN-VTT
      pathway with, consequently, relative hyperactivity of the drive to the
      motoneurons of the elevator muscles, resulting in an upward slow phase. UBN also
      results from lesions affecting the caudal medulla. An area in this region could
      form part of a feedback loop involved in upward gaze-holding, originating in a
      collateral branch of the VTT and comprising the caudal medulla, the flocculus and
      the SVN, successively. Therefore, it is suggested that the main types of
      spontaneous vertical nystagmus due to focal central lesions result from a primary
      dysfunction of the SVN-VTT pathway, which becomes hypoactive after pontine or
      caudal medullary lesions, thereby eliciting UBN, and hyperactive after floccular
      lesions, thereby eliciting DBN. Lastly, since gravity influences UBN and DBN and
      may facilitate the downward vestibular system and restrain the upward vestibular
      system, it is hypothesized that the excitatory SVN-VTT pathway, along with its
      specific floccular inhibition, has developed to counteract the gravity pull. This
      anatomical hyperdevelopment is apparently associated with a physiological upward
      velocity bias, since the gain of all upward slow eye movements is greater than
      that of downward slow eye movements in normal human subjects and in monkeys.

PMID- 15872016
TI  - Homeostatic-like plasticity of the primary motor hand area is impaired in focal
      hand dystonia.
AB  - The excitability of inhibitory circuits in patients with writer's cramp is
      reduced at multiple levels within the sensorimotor system, including the primary
      motor hand area (M1). Although this may play a major role in the pathophysiology
      of writer's cramp, it is still unclear what factors may cause the imbalance
      between inhibition and excitation to arise. One possibility is that homeostatic
      mechanisms that keep cortical excitability within a normal physiological range
      are impaired. In eight patients with writer's cramp and eight healthy age-matched
      controls, we combined low-frequency repetitive transcranial magnetic stimulation
      (rTMS) with transcranial direct current stimulation (TDCS) to probe regional
      homeostatic plasticity of the left M1. Confirming our previous study (Siebner et
      al., J Neurosci 2004; 24: 3379-85), 'facilitatory' preconditioning of the M1 with
      anodal TDCS enhanced the inhibitory effect of subsequent 1 Hz rTMS on
      corticospinal excitability. Conversely, 'inhibitory' preconditioning with
      cathodal TDCS reversed the after effect of 1 Hz rTMS, producing an increase in
      corticospinal excitability. The results were quite different in patients with
      writer's cramp. Following preconditioning with TDCS, 1 Hz rTMS induced no
      consistent changes in corticospinal excitability, indicating a loss of the normal
      'homeostatic' response pattern. In addition, the normal inhibitory effect of
      preconditioning with cathodal TDCS was absent. The present data suggest that
      homeostatic mechanisms that stabilize excitability levels within a useful dynamic
      range are impaired in patients with writer's cramp. We propose that a faulty
      homeostatic response to acute increases in corticospinal excitability favours
      maladaptive motor plasticity. The role of homeostatic-like plasticity in the
      pathophysiology of task-specific dystonias warrants further study.

PMID- 15872017
TI  - Disturbed overt but normal covert shifts of attention in adult cerebellar
      patients.
AB  - In an attempt to provide a common denominator for cognitive deficits observed in
      cerebellar patients, it has been suggested that they might be secondary to
      impaired control of attention, a 'dysmetria of attention', conceptually analogous
      to motor dysmetria. Albeit appealing and quite influential, the concept of
      attentional dysmetria as a consequence of cerebellar disease remains
      controversial. In an attempt to test this concept in a direct way, we compared
      the performance of patients with cerebellar disorders to that of normal controls
      on tasks requiring either overt or covert shifts of spatial attention. In the
      first experiment, visually guided saccades, i.e. overt shifts of spatial
      attention, were elicited. In the second experiment, covert shifts of attention
      were evoked by the need to discriminate the orientation of a Landolt C observed
      during controlled fixation and presented in the same locations as the saccade
      targets in the previous experiment. The allocation of attention was assessed by
      comparing acuity thresholds determined with and without spatial cueing. The
      patients exhibited dysmetric saccades as reflected by larger absolute position
      errors or a higher number of corrective saccades compared to controls. In
      contrast, the ability to shift attention covertly was unimpaired in the patients,
      as indicated by a robust improvement in visual acuity induced by spatial cueing
      which did not differ from the one observed in the controls and which was
      independent of the range of SOAs (stimulus onset asynchronies) tested. Finally,
      the individual amount of saccadic dysmetria did not correlate with the individual
      performance in the covert attentional paradigm. In summary, we conclude that the
      contributions of the cerebellum to attention are confined to overt manifestations
      based on goal-directed eye movements.

PMID- 15872018
TI  - Dog sciatic nerve regeneration across a 30-mm defect bridged by a chitosan/PGA
      artificial nerve graft.
AB  - We have developed a dual-component artificial nerve graft comprising an outer
      microporous conduit of chitosan and internal oriented filaments of polyglycolic
      acid (PGA). The novel graft was used for bridging sciatic nerve across a 30-mm
      defect in six Beagle dogs, which were used as a chitosan/PGA graft group. The
      other Beagle dogs were divided into an autograft group (n = 6) as the positive
      control and a non-grafted group (n = 5) as the negative control. All animals of
      three groups were monitored for changes in their appearance and locomotion
      activities after surgery. Their posture and gait were recorded regularly with the
      aid of photographs and videotapes for each dog. Six months post-operatively, a
      combination of electrophysiological examination, FluoroGold retrograde tracing,
      histological assessment including light microscopy and transmission electron
      microscopy, immunohistochemistry as well as morphometric analyses to both
      regenerated nerves and target muscles was utilized to investigate the nerve
      repair effects of our artificial nerve graft. The results demonstrated that, in
      the chitosan/PGA graft group, the dog sciatic nerve trunk had been reconstructed
      with restoration of nerve continuity and functional recovery, and its target
      skeletal muscle had been re-innervated, improving locomotion activities of the
      operated limb. This study proves the feasibility of the chitosan/PGA artificial
      nerve graft for peripheral nerve regeneration by bridging a longer defect in a
      large animal model.

PMID- 15872019
TI  - Inflammation and primary demyelination induced by the intraspinal injection of
      lipopolysaccharide.
AB  - Inflammation is a prominent feature of several disorders characterized by primary
      demyelination, but it is not clear whether a relationship exists between
      inflammation and myelin damage. We have found that substantial demyelination
      results from the focal inflammatory lesion caused by the injection of
      lipopolysaccharide (LPS; 200 ng) directly into the rat dorsal funiculus. Within
      24 h, such injections caused a focal inflammatory response consisting of a
      substantial number of polymorphonuclear cells and ED1-positive and inducible
      nitric oxide synthase (iNOS)-positive macrophages/microglia. The number of
      inflammatory cells was substantially reduced by day 7. OX-52-positive T-cells
      were less frequently observed but were present in the meninges at 8 h, reached a
      maximum in the dorsal funiculus at 7 days, and were rare at 14 days. The
      inflammation was followed by the appearance of a large lesion of primary
      demyelination that encompassed up to approximately 75% of the cross-sectional
      area of the dorsal funiculus. Treatment with dexamethasone significantly reduced
      the number of cells expressing iNOS, but did not prevent the demyelination. By 28
      days the lesions were largely remyelinated, usually by Schwann cells. These
      changes were not observed in control, saline-injected animals. We conclude that
      the intraspinal injection of LPS results in inflammation and subsequently in
      prominent demyelination. The mechanisms underlying the demyelination are not
      clear, but it is notable that it typically begins with disruption of the adaxonal
      myelin. Indeed, there is an early loss of myelin-associated glycoprotein within
      the lesion, despite the persistence of proteolipid protein. This combination is a
      feature of the pattern III lesion recently described in multiple sclerosis
      (Lucchinetti et al., 2000), and we therefore suggest that LPS-induced
      demyelination may serve as the first experimental model available for the study
      of this type of multiple sclerosis lesion.

PMID- 15872021
TI  - Mutant SOD1 alters the motor neuronal transcriptome: implications for familial
      ALS.
AB  - Familial amyotrophic lateral sclerosis (FALS) is caused, in 20% of cases, by
      mutations in the Cu/Zn superoxide dismutase gene (SOD1). Although motor neuron
      injury occurs through a toxic gain of function, the precise mechanism(s) remains
      unclear. Using an established NSC34 cellular model for SOD1-associated FALS, we
      investigated the effects of mutant SOD1 specifically in cells modelling the
      vulnerable cell population, the motor neurons, without contamination from non
      neuronal cells present in CNS. Using gene expression profiling, 268 transcripts
      were differentially expressed in the presence of mutant human G93A SOD1. Of
      these, 197 were decreased, demonstrating that the presence of mutant SOD1 leads
      to a marked degree of transcriptional repression. Amongst these were a group of
      antioxidant response element (ARE) genes encoding phase II detoxifying enzymes
      and antioxidant response proteins (so-called 'programmed cell life' genes), the
      expression of which is regulated by the transcription factor NRF2. We provide
      evidence that dysregulation of Nrf2 and the ARE, coupled with reduced pentose
      phosphate pathway activity and decreased generation of NADPH, represent
      significant and hitherto unrecognized components of the toxic gain of function of
      mutant SOD1. Other genes of interest significantly altered in the presence of
      mutant SOD1 include several previously implicated in neurodegeneration, as well
      as genes involved in protein degradation, the immune response, cell
      death/survival and the heat shock response. Preliminary studies on isolated motor
      neurons from SOD1-associated motor neuron disease cases suggest key genes are
      also differently expressed in the human disease.

PMID- 15872020
TI  - Cell type analysis of functional fetal dopamine cell suspension transplants in
      the striatum and substantia nigra of patients with Parkinson's disease.
AB  - We report the first post-mortem analysis of two patients with Parkinson's disease
      who received fetal midbrain transplants as a cell suspension in the striatum, and
      in one case also in the substantia nigra. These patients had a favourable
      clinical evolution and positive 18F-fluorodopa PET scans and did not develop
      motor complications. The surviving transplanted dopamine neurons were positively
      identified with phenotypic markers of normal control human substantia nigra (n =
      3), such as tyrosine hydroxylase, G-protein-coupled inward rectifying current
      potassium channel type 2 (Girk2) and calbindin. The grafts restored the cell type
      that provides specific dopaminergic innervation to the most affected striatal
      regions in the parkinsonian brain. Such transplants were able to densely
      reinnervate the host putamen with new dopamine fibres. The patients received only
      6 months of standard immune suppression, yet by post-mortem analysis 3-4 years
      after surgery the transplants appeared only mildly immunogenic to the host brain,
      by analysis of microglial CD45 and CD68 markers. This study demonstrates that,
      using these methods, dopamine neuronal replacement cell therapy can be beneficial
      for patients with advanced disease, and that changing technical approaches could
      have a favourable impact on efficacy and adverse events following neural
      transplantation.

PMID- 15872022
TI  - Smooth quantile ratio estimation with regression: estimating medical expenditures
      for smoking-attributable diseases.
AB  - The methodological development of this paper is motivated by a common problem in
      econometrics where we are interested in estimating the difference in the average
      expenditures between two populations, say with and without a disease, as a
      function of the covariates. For example, let Y(1) and Y(2) be two non-negative
      random variables denoting the health expenditures for cases and controls. Smooth
      Quantile Ratio Estimation (SQUARE) is a novel approach for estimating
      Delta=E[Y(1)] - E[Y(2)] by smoothing across percentiles the log-transformed ratio
      of the two quantile functions. Dominici et al. (2005) have shown that SQUARE
      defines a large class of estimators of Delta, is more efficient than common
      parametric and nonparametric estimators of Delta, and is consistent and
      asymptotically normal. However, in applications it is often desirable to estimate
      Delta(x)=E[Y(1)|x]--E[Y(2)|x], that is, the difference in means as a function of
      x. In this paper we extend SQUARE to a regression model and we introduce a two
      part regression SQUARE for estimating Delta(x) as a function of x. We use the
      first part of the model to estimate the probability of incurring any costs and
      the second part of the model to estimate the mean difference in health
      expenditures, given that a nonzero cost is observed. In the second part of the
      model, we apply the basic definition of SQUARE for positive costs to compare
      expenditures for the cases and controls having 'similar' covariate profiles. We
      determine strata of cases and control with 'similar' covariate profiles by the
      use of propensity score matching. We then apply two-part regression SQUARE to the
      1987 National Medicare Expenditure Survey to estimate the difference Delta(x)
      between persons suffering from smoking-attributable diseases and persons without
      these diseases as a function of the propensity of getting the disease. Using a
      simulation study, we compare frequentist properties of two-part regression SQUARE
      with maximum likelihood estimators for the log-transformed expenditures.

PMID- 15872023
TI  - HIV-1-specific IFN-gamma/IL-2-secreting CD8 T cells support CD4-independent
      proliferation of HIV-1-specific CD8 T cells.
AB  - Functional and phenotypic characterization of virus-specific CD8 T cells against
      cytomegalovirus, Epstein-Barr virus, influenza (flu), and HIV-1 were performed on
      the basis of the ability of CD8 T cells to secrete IFN-gamma and IL-2, to
      proliferate, and to express CD45RA and CCR7. Two functional distinct populations
      of CD8 T cells were identified: (i) dual IFN-gamma/IL-2-secreting cells and (ii)
      single IFN-gamma-secreting cells. Virus-specific IFN-gamma/IL-2-secreting CD8 T
      cells were CD45RA-CCR7-, whereas single IFN-gamma CD8 T cells were either CD45RA
      CCR7- or CD45RA+CCR7-. The proportion of virus-specific IFN-gamma/IL-2-secreting
      CD8 T cells correlated with that of proliferating CD8 T cells, and the loss of
      HIV-1-specific IL-2-secreting CD8 T cells was associated with that of HIV-1
      specific CD8 T cell proliferation. Substantial proliferation of virus-specific
      CD8 T cells (including HIV-1-specific CD8 T cells) was also observed in CD4 T
      cell-depleted populations or after stimulation with MHC class I tetramer-peptide
      complexes. IL-2 was the factor responsible for the CD4-independent CD8 T cell
      proliferation. These results indicate that IFN-gamma/IL-2-secreting CD8 T cells
      may promote antigen-specific proliferation of CD8 T cells even in the absence of
      helper CD4 T cells.

PMID- 15872024
TI  - Getting evidence into practice: what works in developing countries?
AB  - PURPOSE: We summarize and comment on the available literature on the
      effectiveness of interventions designed to change professional behaviour in order
      to bring evidence into practice in developing countries. DATA SOURCES: We used a
      strategy adapted from the Effective Practice & Organization Care (EPOC) Cochrane
      group. STUDY SELECTION: Forty-four studies met pre-defined selection criteria.
      Controlled and uncontrolled trials of interventions were included. Studies
      measured either professional compliance with agreed standards or patients'
      clinical outcomes. Data extraction. Data were extracted using a pre-defined
      extraction tool and studies were appraised accordingly. RESULTS OF DATA
      SYNTHESIS: Data were synthesized and categorized according to different types of
      intervention. Audit and feedback was found to be effective, at least in the short
      term, when combined with other approaches. Similarly, educational interventions
      were more effective when designed to address local educational needs and
      organizational barriers. We found insufficient evidence to assess the
      effectiveness of educational outreach, local opinion leaders, use of mass media,
      and reminders. Educational materials alone are unlikely to influence change.
      However, the majority of studies had weak designs and failed to exclude possible
      biases. CONCLUSION: Current evidence for the effectiveness of interventions to
      change health professionals' behaviour in developing countries is either scanty
      or flawed due to poorly designed research. Given the recent drive to improve
      quality of care, this should be a priority area for researchers and international
      agencies supporting health systems development in developing countries. This
      review provides an insight into some of the methodological issues that interested
      researchers may face.

PMID- 15872025
TI  - Management of suspected venous thromboembolism: the impact of a multifaceted
      intervention.
AB  - OBJECTIVE: To achieve a common strategy in the event of a suspected venous
      thromboembolism. DESIGN: A multifaceted intervention, combining an audit strategy
      and implementation of local guidelines: phase 1, the first step, consisted of a 6
      month audit to identify dysfunction; during phase 2, intervention, local
      guidelines were formulated by a working group and then implemented; phase 3
      consisted of a re-audit over a 6-month period following the intervention.
      SETTING: A tertiary hospital, France. PARTICIPANTS: 419 patients with suspected
      venous thromboembolism in phase 1; 287 patients with suspected pulmonary embolism
      in phase 3. RESULTS: First phase: a dysfunction was observed in three of five
      criteria under study: (i) the diagnostic procedure lasted more than 48 hours in
      114 patients (27.2%); (ii) no anticoagulant therapy at the time of suspicion in
      116 patients (27.7%); (iii) an inconclusive lung scan without further testing in
      the event of a suspected pulmonary embolism in 40 patients (14%); the
      intervention phase was thus restricted to the management of suspected pulmonary
      embolism; similar results were found during the phase 3 re-audit. CONCLUSION: No
      improvement in the diagnostic work-up in the event of a suspected pulmonary
      embolism was observed following this multifaceted intervention.

PMID- 15872026
TI  - Concept mapping: an introduction to structured conceptualization in health care.
AB  - Structured conceptualization is a specific form of concept mapping that is a
      mixed methods participatory approach that combines group processes
      (brainstorming, sorting, group interpretation) with a sequence of multivariate
      statistical analyses (multidimensional scaling, hierarchical cluster analysis).
      Concept mapping's relevance to health care quality and services is described. The
      basic steps and analysis sequence in the concept mapping method are outlined and
      a brief example of the results for a health planning project are presented.
      Several examples of the use of concept mapping in health are provided.

PMID- 15872027
TI  - Timing of arrhythmic death after myocardial infarction: does it affect timing of
      ICD implantation?

PMID- 15872028
TI  - Significant differential effects of lower doses of hormone therapy or tibolone on
      markers of cardiovascular disease in post-menopausal women: a randomized, double
      blind, crossover study.
AB  - AIMS: We have previously reported that lower doses of hormone therapy (L-HT) and
      tibolone have different effects on markers of cardiovascular disease when
      compared with conventional doses of HT. The objective was to compare the effects
      of L-HT and tibolone on lipid profile, vasodilation, and factors associated with
      inflammation and haemostasis. METHODS AND RESULTS: Forty-one women received a
      combination of micronized progesterone 100 mg with conjugated equine estrogen 0.3
      mg vs. tibolone 2.5 mg alone daily in random order during 2 months with 2 months
      washout period. When compared with L-HT, tibolone significantly reduced total
      cholesterol (P<0.001), triglyceride (P<0.001), HDL cholesterol (P<0.001) levels,
      and triglyceride/HDL cholesterol ratios (P=0.004) except total cholesterol/HDL
      cholesterol ratios. Tibolone improved flow-mediated response to hyperaemia from
      baseline values (P<0.001) by a similar magnitude to L-HT. L-HT and tibolone did
      not increase high-sensitivity C-reactive protein relative to baseline values. L
      HT reduced antithrombin III from baseline values (P=0.037), compared with
      tibolone showing no changes. However, there was no difference between either. In
      contrast, tibolone increased pro-thrombin fragment 1+2 (F1+2) from baseline
      values (P=0.002), compared with L-HT showing no changes. Tibolone significantly
      reduced plasma plasminogen activator inhibitor type 1 (PAI-1) antigen levels from
      baseline values (P=0.004), compared with L-HT showing no changes. The effects of
      L-HT and tibolone on F1+2 and PAI-1 were significantly different (P=0.045 and
      P=0.008, respectively). CONCLUSION: Both tibolone and L-HT improved flow-mediated
      response by a similar magnitude and did not significantly increase high
      sensitivity C-reactive protein. However, tibolone significantly reduced PAI-1,
      but increased F1+2 more than L-HT.

PMID- 15872029
TI  - Effect of bezafibrate on incidence of type 2 diabetes mellitus in obese patients.
AB  - AIMS: To assess the effect of fibric acid derivative bezafibrate on incidence of
      type 2 diabetes in obese patients over a median 6.3 years follow-up period.
      METHODS AND RESULTS: The study sample comprised 339 non-diabetic obese patients
      (body mass index > or = 30.0 kg/m2) aged 42-74. Patients received either
      bezafibrate retard 400 mg (178 patients) or placebo (161 patients) once daily.
      Development of new diabetes was recorded in 98 patients: in 56 (37.0%) from the
      placebo group vs. 42 (27.1%) from the bezafibrate group, (P log-rank=0.01). The
      median time (interquartile range) until onset of new diabetes was significantly
      delayed in patients on bezafibrate when compared with those on placebo: 4.0 (2.1
      5.0) vs. 2.0 (0.5-3.5) years, P=0.002. Multivariable analysis identified
      bezafibrate treatment as an independent predictor of reduced risk of new diabetes
      with hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.39-0.91]. Other
      significant variables associated with future overt type 2 diabetes in obese
      patients were triglycerides (50 mg/dL increment) with HR 1.15 (95% CI 1.02-1.28)
      and fasting glucose (10 mg/dL increment) with HR 2.27 (95% CI 1.83-2.81).
      CONCLUSION: Bezafibrate, when compared with placebo, reduced the incidence and
      delayed the onset of type 2 diabetes in obese patients over a long-term follow-up
      period.

PMID- 15872030
TI  - Perindopril in diabetes: perspective from the EUROPA substudy, PERSUADE.

PMID- 15872031
TI  - New insights in minimally invasive valve replacement: description of a
      cooperative approach for the off-pump replacement of mitral valves.
AB  - AIMS: The aim of the present study was to evaluate whether off-pump mini-invasive
      mitral valve replacement is possible after prior bioprosthetic mitral valve
      replacement in animals. METHODS AND RESULTS: To validate this concept for off
      pump redo mitral valve insertion, we first replaced surgically mitral valves of
      six sheep under extracorporeal circulation using a Mosaic valve. Prior to its
      insertion, we added a radio-opaque ring on its base to enhance its visualization
      under fluoroscopy. A bovine jugular valve mounted into a stent was then inserted
      off-pump through an opening of the atrial wall. Mitral valves were replaced
      successfully in all animals. Following the surgical valve insertion, mean left
      atrium and left ventricular end-diastolic pressures were 38 (22-42) and 18.8 mmHg
      (13-22), respectively. Angiography showed perfectly functioning valves, no
      subaortic valve obstruction, and a mild paravalvular leak in one animal. In one
      animal, we were unable to control the bleeding from the atrial opening. In this
      case, trans-atrial valvulation was not attempted. The off-pump valvular
      implantation was successful in the other five sheep. Haemodynamic data did not
      change after the insertion of valved stents. Implanted valves were all competent.
      The animal with the better haemodynamics was kept alive and is still alive 3
      months after implantation. CONCLUSION: Surgically implanted bioprosthetic valves
      provide excellent support for off-pump insertion of a valved stent. Further
      experiments are necessary, in particular with appropriate valve size, before
      considering this approach for percutaneous mitral valvular replacement in
      patients with a dysfunctional bioprosthesis.

PMID- 15872032
TI  - Rate-control vs. rhythm-control in patients with atrial fibrillation: a meta
      analysis.
AB  - AIMS: To systematically assess the risk/benefit ratio of a rate-control strategy
      vs. a rhythm-control strategy in patients with first or recurrent atrial
      fibrillation (AF). METHODS AND RESULTS: We searched Medline, CENTRAL, and other
      sources up to September 2004 for randomized trials. Individual and pooled random
      effect odd ratios (OR) and 95% confidence intervals (CI) [OR (95% CI)] were
      calculated for the combined endpoint of all cause death and thromboembolic stroke
      (CEP), major bleeds (intra and extracranial), and systemic embolism. Number
      needed to treat (NNT) to avoid one CEP and heterogeneity were also assessed. Five
      studies enrolling 5239 patients with AF compared rate-control vs. rhythm-control.
      Average follow-up ranged from 1 to 3.5 years. A rate-control strategy compared
      with a rhythm-control approach was associated with a significantly reduced risk
      of CEP [OR 0.84 (0.73, 0.98), P=0.02], and with a trend towards a reduced risk of
      death [OR 0.87 (0.74, 1.02), P=0.09] and thromboembolic stroke [OR 0.80 (0.6,
      1.07), P=0.14]. NNT to save one CEP was 50. There was no significant difference
      in the risk of major bleeds [OR 1.14 (0.9, 1.45), P=0.28] and systemic embolism
      [OR 0.93 (0.43, 2.02), P=0.90]. No significant heterogeneity was found in any of
      the analyses (P>0.1). CONCLUSION: This meta-analysis of 5239 patients with AF
      indicates that an initial rate-control strategy compared with a rhythm-control
      one is associated with a better prognosis, thus representing the standard
      treatment against which to test new therapeutic approaches.

PMID- 15872033
TI  - Transient reduction in myocardial free oxygen radical levels is involved in the
      improved cardiac function and structure after long-term allopurinol treatment
      initiated in established chronic heart failure.
AB  - AIMS: Oxidative stress, i.e. imbalance between reactive oxygen species (ROS) and
      antioxidant defences, contributes to the progression of chronic heart failure
      (CHF). Acute inhibition of xanthine oxidase (XO), which produces ROS, improves
      mechanical efficiency of the failing heart, but whether long-term XO inhibition
      exerts beneficial effects in CHF is unknown. METHODS AND RESULTS: In rats with
      established CHF induced by left coronary ligation, we assessed the effects of a 5
      day and a 10-week treatment with the XO inhibitor allopurinol (50 mg kg(-1) day(
      1)) on haemodynamics and left ventricular (LV) function and structure. Both acute
      and chronic allopurinol treatment increase cardiac output without modification of
      arterial pressure, but only chronic allopurinol treatment reduces LV end
      diastolic pressure and LV relaxation constant. Chronic allopurinol treatment
      decreases both LV systolic and diastolic diameters, but acute allopurinol
      treatment only decreases LV systolic diameter. Moreover, chronic allopurinol
      decreases LV weight and collagen density. Despite XO inhibition after acute and
      chronic allopurinol treatment, as both treatments reduce uric acid plasma levels,
      only acute allopurinol treatment reduces LV ROS determined using electron spin
      resonance spectroscopy. However, the CHF-enhanced myocardial thiobarbituric acid
      reactive substances levels were never modified. CONCLUSION: In experimental CHF,
      long-term allopurinol treatment, initiated in a pathological state of overt CHF,
      improves LV haemodynamics and function and prevents LV remodelling. These long
      term effects are, at least partially, caused by a transient reduction of
      myocardial ROS shortly after initiation of allopurinol treatment, but whether
      other mechanism(s), independent of myocardial redox 'status', such as reduced
      inflammation, are implicated remains to be confirmed.

PMID- 15872034
TI  - Reduction of treatment delay in patients with ST-elevation myocardial infarction:
      impact of pre-hospital diagnosis and direct referral to primary percutaneous
      intervention.

PMID- 15872035
TI  - Heating of pacemaker leads during magnetic resonance imaging.

PMID- 15872036
TI  - Prognostic significance of blood markers of inflammation in patients with ST
      segment elevation myocardial infarction undergoing primary angioplasty and
      effects of pexelizumab, a C5 inhibitor: a substudy of the COMMA trial.
AB  - AIMS: Pexelizumab, a monoclonal antibody inhibiting C5, reduced 90 day mortality
      and shock in the COMplement inhibition in Myocardial infarction treated with
      Angioplasty (COMMA) trial without apparent reductions in infarct size.
      Inflammation is a critical component of ST-elevation myocardial infarction
      (STEMI); this substudy examines prognostic values of selected markers and
      treatment effects. METHODS AND RESULTS: C-reactive protein, interleukin-6 (IL-6),
      and tumour necrosis factor-alpha (TNF-alpha) serum levels were assessed in 337
      patients enrolled in either the placebo or the pexelizumab 24 h infusion group.
      Higher C-reactive protein and IL-6 levels at baseline, 24 h, and 72 h were
      strongly associated with increased subsequent death (P<0.002 at baseline and 24
      h, P<0.02 at 72 h); and all baseline marker levels with death or cardiogenic
      shock (P<0.03) within 90 days. C-reactive protein and IL-6 levels were similar at
      baseline, but significantly lower 24 h later with pexelizumab, when compared with
      placebo (17.1 vs. 25.5 mg/L, P=0.03 and 51.0 vs. 63.8 pg/mL, P=0.04,
      respectively). At 72 h, corresponding levels were similar, whereas TNF-alpha was
      slightly higher (P=0.04) in the treated group. CONCLUSION: Inflammation markers
      and their serial changes predict death and shock in patients with STEMI
      undergoing primary angioplasty. Pexelizumab reduced C-reactive protein and IL-6,
      suggesting treatment benefits mediated through anti-inflammatory effects.

PMID- 15872038
TI  - Enhancement of perfusion reserve by cardiac resynchronization therapy.

PMID- 15872039
TI  - ASD closure for migraine: is there a scientific basis?

PMID- 15872040
TI  - Differential distribution of functional alph}1-adrenergic receptor subtypes along
      the rat tail artery.
AB  - The rat tail artery has been used for the study of vasoconstriction mediated by
      alpha(1A)-adrenoceptors (ARs). However, rings from proximal segments of the tail
      artery (within the initial 4 cm, PRTA) were at least 3-fold more sensitive to
      methoxamine and phenylephrine (n = 6-12; p < 0.05) than rings from distal parts
      (between the sixth and 10th cm, DRTA). Interestingly, the imidazolines N-[5-(4,5
      dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1
      yl]methanesulfonamide hydrobromide (A-61603) and oxymetazoline, which activate
      selectively alpha(1A)-ARs, were equipotent in PRTA and DRTA (n = 4-12), whereas
      buspirone, which activates selectively alpha(1D)-AR, was approximately 70-fold
      more potent in PRTA than in DRTA (n = 8; p < 0.05). The selective alpha(1D)-AR
      antagonist 8-[2-[4-(methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9
      dione dihydrochloride (BMY-7378) was approximately 70-fold more potent against
      the contractions induced by phenylephrine in PRTA (pK(B) of approximately 8.45; n
      = 6) than in DRTA (pK(B) of approximately 6.58; n = 6), although the antagonism
      was complex in PRTA. 5-Methylurapidil, a selective alpha(1A)-antagonist, was
      equipotent in PRTA and DRTA (pK(B) of approximately 8.4), but the Schild slope in
      DRTA was 0.73 +/- 0.05 (n = 5). The noncompetitive alpha(1B)-antagonist conotoxin
      rho-TIA reduced the maximal contraction induced by phenylephrine in DRTA, but not
      in PRTA. These results indicate a predominant role for alpha(1A)-ARs in the
      contractions of both PRTA and DRTA but with significant coparticipations of
      alpha(1D)-ARs in PRTA and alpha(1B)-ARs in DRTA. Semiquantitative reverse
      transcription-polymerase chain reaction revealed that mRNA encoding alpha(1A)-
      and alpha(1B)-ARs are similarly distributed in PRTA and DRTA, whereas mRNA for
      alpha(1D)-ARs is twice more abundant in PRTA. Therefore, alpha(1)-ARs subtypes
      are differentially distributed along the tail artery. It is important to consider
      the segment from which the tissue preparation is taken to avoid
      misinterpretations on receptor mechanisms and drug selectivities.

PMID- 15872041
TI  - Disodium Disuccinate Astaxanthin (Cardax) attenuates complement activation and
      reduces myocardial injury following ischemia/reperfusion.
AB  - Carotenoids are a naturally occurring group of compounds that possess antioxidant
      properties. Most natural carotenoids display poor aqueous solubility and tend to
      form aggregates in solution. Disodium disuccinate astaxanthin (DDA; Cardax) is a
      water-dispersible synthetic carotenoid that rapidly and preferentially associates
      with serum albumin, thereby preventing the formation of supramolecular complexes
      and facilitating its efficacy after parenteral administration. This study
      investigated the ability of DDA to reduce inflammation and myocardial injury in a
      rabbit model of ischemia/reperfusion. DDA (50 mg/kg/day) or saline was
      administered i.v. for 4 consecutive days before the initiation of the protocol
      for induction of myocardial ischemia/reperfusion. On the 5th day, rabbits
      underwent 30 min of coronary artery occlusion, followed by a 3-h reperfusion
      period. Myocardial infarct size, as a percentage of the area at risk, was
      calculated for both groups. Infarct size was 52.5 +/- 7.5% in the vehicle-treated
      (n = 9) and 25.8 +/- 4.7% in the DDA-treated (n = 9) animals (p < 0.01 versus
      vehicle; mean myocardial salvage = 51%). To evaluate the anti-inflammatory
      effects of DDA, complement activity was assessed at the end of reperfusion using
      a red blood cell lysis assay. DDA administration significantly reduced (p < 0.01)
      the activation of the complement system in the serum. The current results,
      coupled with the well established antioxidant ability of carotenoids, suggest
      that the mechanism(s) of action by which DDA reduces the tissue damage associated
      with reperfusion injury may include both antioxidant and anticomplement
      components.

PMID- 15872042
TI  - VPAC2 receptors mediate vasoactive intestinal peptide-induced neuroprotection
      against neonatal excitotoxic brain lesions in mice.
AB  - Prepro-vasoactive intestinal peptide (VIP) mRNA codes for two neuropeptides: VIP
      and peptide histidine isoleucine (PHI). Two VIP receptors, shared with a similar
      affinity by pituitary adenylate cyclase-activating polypeptide (PACAP), have been
      cloned: VPAC(1) and VPAC(2). PHI binds to these receptors with a lower affinity.
      VPAC receptors are classically associated with a cAMP-dependent pathway, although
      other pathways, including calcium mobilization and protein kinase C activation
      have been described. We previously showed that intracerebral administration of
      the glutamate agonist ibotenate to postnatal day 5 mice induces white matter
      lesions mimicking human periventricular leukomalacia. In this model, coinjection
      of VIP protects against white matter lesions. This neuroprotection is independent
      from cAMP and is mediated by protein kinase C. Using this model, this study aimed
      to determine the receptor involved in VIP-induced neuroprotection. VIP effects
      were mimicked with a similar potency by VPAC(2) agonists and PHI but not by
      VPAC(1) agonists, PACAP 27, or PACAP 38. VIP neuroprotective effects were lost in
      mice lacking VPAC(2) receptor. In situ hybridization confirmed the presence of
      VPAC(2) mRNA in the postnatal day 5 white matter. When analyzed between embryonic
      life and adulthood, VIP-specific binding site density peaked at postnatal day 5.
      These data suggest that, in this model, VIP-induced neuroprotection is mediated
      by VPAC(2) receptors. The pharmacology of this VPAC(2) receptor seems
      unconventional because 1) PACAP does not mimic VIP effects, 2) PHI acts with a
      comparable potency, and 3) PACAP 27 modestly inhibited the VIP-specific binding,
      whereas for PHI or VIP, inhibition was complete.

PMID- 15872043
TI  - Comparative in vitro antimicrobial activity of a new carbapenem, doripenem:
      tentative disc diffusion criteria and quality control.
AB  - OBJECTIVES: To determine the spectrum of activity of doripenem and to propose
      tentative MIC and disc diffusion breakpoints. METHODS: The in vitro
      susceptibilities of 2137 bacterial isolates, representing 28 different species,
      to doripenem, imipenem and meropenem were determined by the NCCLS broth
      microdilution and disc diffusion testing methods. RESULTS: The doripenem
      MIC(50)s/(90)s were (in mg/L) for Enterobacteriaceae, 0.06/0.25; Pseudomonas
      aeruginosa, 0.25/1; Haemophilus influenzae, 0.12/0.5; streptococci, 0.016/0.5 and
      for staphylococci, 0.06/4. Like other carbapenems tested, doripenem
      MIC(50)s/(90)s were >32/>32 and 0.5/32 mg/L for the enterococci and non
      fermentative Gram-negative bacilli (excluding P. aeruginosa), respectively.
      Against members of the Enterobacteriaceae and H. influenzae, doripenem was
      generally more active than imipenem and the same as or slightly less active than
      meropenem. Values for the non-fermentative Gram-negative bacilli excluding P.
      aeruginosa were comparable for all three carbapenems. Doripenem MICs increased
      with increasing resistance to methicillin (staphylococci), penicillin
      (streptococci) and strains that were beta-lactamase-negative ampicillin-resistant
      (Haemophilus). Doripenem exhibits excellent activity against extended-spectrum
      beta-lactamase-producing strains of Escherichia coli and Klebsiella spp. The
      NCCLS disc diffusion test was performed simultaneously on all organisms.
      CONCLUSIONS: Assuming the MIC susceptible breakpoints for doripenem are < or =1
      mg/L for the streptococci and < or =2 mg/L for all other genera, then disc
      diffusion zone diameter breakpoints can be proposed. In addition, MIC and/or disc
      diffusion quality control ranges of doripenem were determined for 10 ATCC
      reference strains.

PMID- 15872044
TI  - Revised Ambler classification of {beta}-lactamases.

PMID- 15872045
TI  - Antisense phosphorodiamidate morpholino oligomer inhibits viability of
      Escherichia coli in pure culture and in mouse peritonitis.
AB  - OBJECTIVES: Antisense phosphorodiamidate morpholino oligomers (PMOs) are
      synthetic DNA mimics that specifically inhibit gene expression in pure cultures
      of Escherichia coli. Previously, an 11 base PMO targeted to an essential gene
      (acpP) for phospholipid biosynthesis was shown to inhibit growth of a pure
      culture of E. coli AS19, which has an abnormally permeable outer membrane. The
      objectives of experiments in this report are to show that the AcpP PMO
      significantly inhibits growth of strain SM105, which has a normal, intact outer
      membrane, both in pure culture and in infected mice. METHODS: In pure culture,
      SM105 was grown in rich broth supplemented with 20 muM AcpP PMO, and growth was
      monitored by optical density and viable cell count. Mice were infected by
      intraperitoneal injection with a non-lethal inoculum of either E. coli AS19 or
      SM105. Following infection, mice were treated intraperitoneally with 300 mug of
      the 11 base antisense PMO targeted to acpP, a scrambled sequence PMO or PBS.
      RESULTS: Growth of SM105 was slower and viable cells were significantly reduced
      by up to 61% in pure cultures supplemented with AcpP PMO compared with untreated
      cultures or cultures supplemented with a scrambled sequence PMO. A single dose of
      AcpP PMO reduced peritoneal cfu of E. coli AS19 about 39- to 600-fold compared
      with controls at 2, 7, 13 and 23 h after treatment. The same PMO significantly
      reduced cfu of E. coli SM105 75% compared with controls at 12 h after treatment.
      However, there was no difference in cfu at 2, 7 or 24 h. A second dose at 24 h
      again reduced SM105 cfu about 10-fold by 48 h post-infection. In other
      experiments with infected mice, multiple doses of AcpP PMO sustained the
      approximately 10-fold reduction in SM105 cfu at 6, 12 and 24 h post-infection.
      Compared with equivalent (micromolar) doses of ampicillin, AcpP PMO was
      significantly more effective at all time points. Specificity of PMO inhibition
      was shown in other experiments by treating infected mice with a PMO targeted to a
      non-essential reporter gene for luciferase. A luciferase-specific PMO reduced
      both the amount and activity of luciferase to the same extent, whereas scrambled
      PMO had no effect. CONCLUSIONS: An 11 base antisense PMO targeted to acpP
      significantly inhibited viability of a strain of E. coli with a normal, intact
      outer membrane both in pure culture and in infected mice. Inhibition by PMOs was
      sequence-specific.

PMID- 15872046
TI  - Genetic analysis of pbp2x in clinical Streptococcus pneumoniae isolates in
      Quebec, Canada.
AB  - OBJECTIVES: To investigate the nature of the amino acid motifs found in
      penicillin-binding protein (PBP) 2x of penicillin-resistant Streptococcus
      pneumoniae isolates across the province of Quebec (Canada), and to obtain
      preliminary information regarding the prevalence of these alterations. METHODS:
      The pbp2x genomic region encompassing codons 178-703, which includes the entire
      region of the transpeptidase domain, was sequenced and compared for 52 clinical
      isolates comprising 20 penicillin-susceptible (PSSP), 20 penicillin-intermediate
      (PISP) and 12 penicillin-resistant (PRSP) pneumococci. RESULTS: The degree of
      diversity within PBP2x correlated with increased resistance to beta-lactam
      antibiotics. There were an average of 5.0 +/- 1.8 mutations in PSSP, 37.9 +/- 4.4
      in PISP, and 63.0 +/- 2.0 in PRSP isolates when compared with the control
      penicillin-susceptible strain R6. At least six distinct amino acid profiles were
      identified among PISP strains isolated in Quebec. In contrast, all PRSP isolates
      shared a similar pattern of altered amino acids compared with the sequence from
      susceptible strains. CONCLUSIONS: These data will be useful in future studies to
      monitor the genetic changes associated with the emergence and spread of beta
      lactam resistance in Quebec.

PMID- 15872047
TI  - Increasing ceftriaxone resistance in Salmonella isolates from a university
      hospital in Taiwan.
AB  - OBJECTIVES: Salmonella infection is a distressing health problem worldwide. This
      study reports the changing epidemiology of Salmonella infections in Taiwan during
      1999-2003, with emphasis on increasing ceftriaxone resistance. METHODS: Records
      of Salmonella clinical isolates in Chang Gung Memorial Hospital during 1999-2003
      were reviewed. All isolates were identified and antimicrobial susceptibility
      determined by standard methods. A total of 22 ceftriaxone-resistant isolates were
      investigated by PCR sequencing of the bla(TEM), bla(SHV), bla(CTX-M) and ampC
      genes. Southern-blot hybridization was used to localize the ampC gene. Infrequent
      restriction-site PCR was used to genotype these isolates. RESULTS: A total of
      3635 Salmonella isolates, including 3592 (98.8%) non-typhoid Salmonella, were
      identified. Serogroup B (55.6%) remained the most predominant, but the prevalence
      has been decreasing. In contrast, serogroup D infections have increased
      significantly from 13.6 to 22.8%. Overall resistance to ampicillin and
      chloramphenicol remained high, with the highest rate (91% to both drugs) observed
      in Salmonella enterica serotype Choleraesuis in 2003. A sudden upsurge of
      ciprofloxacin resistance from zero to 69% was found in S. Choleraesuis.
      Ceftriaxone resistance increased in several serogroups (0.8-2.1%; average, 1.5%).
      The resistance was associated with plasmid-mediated bla(CMY-2) in 14 cases and
      extended-spectrum beta-lactamases (ESBLs), including CTX-M-3 (n=6), SHV-2a (n=1)
      and SHV-12 (n=1), in others. Diverse serotypes and genotypes were found among the
      ceftriaxone-resistant isolates. CONCLUSIONS: Increasing ceftriaxone resistance in
      non-typhoid Salmonella appears to link to the spread of plasmid-mediated ampC or
      ESBL genes. Effective measures should be taken to prevent the problem worsening.

PMID- 15872048
TI  - Localization of cytochrome P450 CYP2S1 expression in human tissues by in situ
      hybridization and immunohistochemistry.
AB  - CYP2S1 is a recently discovered dioxin-inducible member of the cytochrome P450
      superfamily. It has been shown to be involved in the metabolism of some aromatic
      hydrocarbons as well as retinoic acid, suggesting a role in biotransformation of
      both exogenous and endogenous compounds. In this study, we used mRNA in situ
      hybridization and immunohistochemistry to investigate the cellular localization
      of CYP2S1 in various human tissues using tissue microarrays. High expression
      levels were observed mainly in epithelial cell types, especially in the epithelia
      frequently exposed to xenobiotics. In the respiratory tract, the expression was
      strong in nasal cavity, bronchi, and bronchioli, whereas it was low in the
      alveolar lining cells. Similarly, CYP2S1 was highly expressed in the epithelial
      cells throughout the gastrointestinal tract. Strong epithelial expression was
      also observed in uterine cervix, urinary bladder, and skin. In many exocrine
      glands (e.g., adrenal gland and pancreas), secretory epithelial cells showed
      moderate to strong expression levels. In the liver, the expression was low.
      CYP2S1 was highly expressed in epithelial cells that are major targets for
      carcinogen exposure and common progenitor cells to tumor development. Indeed, we
      found strong CYP2S1 expression in many tumors of epithelial origin.

PMID- 15872049
TI  - Tissue-specific tropomyosin isoform composition.
AB  - Four distinct genes encode tropomyosin (Tm) proteins, integral components of the
      actin microfilament system. In non-muscle cells, over 40 Tm isoforms are derived
      using alternative splicing. Distinct populations of actin filaments characterized
      by the composition of these Tm isoforms are found differentially sorted within
      cells (Gunning et al. 1998b). We hypothesized that these distinct intracellular
      compartments defined by the association of Tm isoforms may allow for independent
      regulation of microfilament function. Consequently, to understand the molecular
      mechanisms that give rise to these different microfilaments and their regulation,
      a cohort of fully characterized isoform-specific Tm antibodies was required. The
      characterization protocol initially involved testing the specificity of the
      antibodies on bacterially produced Tm proteins. We then confirmed that these Tm
      antibodies can be used to probe the expression and subcellular localization of
      different Tm isoforms by Western blot analysis, immunofluorescence staining of
      cells in culture, and immunohistochemistry of paraffin wax-embedded mouse
      tissues. These Tm antibodies, therefore, have the capacity to monitor specific
      actin filament populations in a range of experimental systems.

PMID- 15872050
TI  - SPARC-thrombospondin-2-double-null mice exhibit enhanced cutaneous wound healing
      and increased fibrovascular invasion of subcutaneous polyvinyl alcohol sponges.
AB  - Secreted protein acidic and rich in cysteine (SPARC) and thrombospondin-2 (TSP-2)
      are structurally unrelated matricellular proteins that have important roles in
      cell-extracellular matrix (ECM) interactions and tissue repair. SPARC-null mice
      exhibit accelerated wound closure, and TSP-2-null mice show an overall
      enhancement in wound healing. To assess potential compensation of one protein for
      the other, we examined cutaneous wound healing and fibrovascular invasion of
      subcutaneous sponges in SPARC-TSP-2 (ST) double-null and wild-type (WT) mice.
      Epidermal closure of cutaneous wounds was found to occur significantly faster in
      ST-double-null mice, compared with WT animals: histological analysis of dermal
      wound repair revealed significantly more mature phases of healing at 1, 4, 7, 10,
      and 14 days after wounding, and electron microscopy showed disrupted ECM at 14
      days in these mice. ST-double-null dermal fibroblasts displayed accelerated
      migration, relative to WT fibroblasts, in a wounding assay in vitro, as well as
      enhanced contraction of native collagen gels. Zymography indicated that
      fibroblasts from ST-double-null mice also produced higher levels of matrix
      metalloproteinase (MMP)-2. These data are consistent with the increased
      fibrovascular invasion of subcutaneous sponge implants seen in the double-null
      mice. The generally accelerated wound healing of ST-double-null mice reflects
      that described for the single-null animals. Importantly, the absence of both
      proteins results in elevated MMP-2 levels. SPARC and TSP-2 therefore perform
      similar functions in the regulation of cutaneous wound healing, but fine-tuning
      with respect to ECM production and remodeling could account for the enhanced
      response seen in ST-double-null mice.

PMID- 15872051
TI  - Arylamine N-acetyltransferase 2 expression in the developing heart.
AB  - Murine arylamine N-acetyltransferase 2 (NAT2) is expressed in the developing
      heart and in the neural tube at the time of closure. Classically described as a
      xenobiotic metabolizing enzyme, there is increasing evidence for a distinct
      biological role for murine NAT2. We have characterized the expression of
      arylamine N-acetyltransferase 2 during cardiogenesis, mapping its expression in
      vivo, using a lacZ insertion deletion, and also in vitro, by measuring NAT2
      enzyme activity. These findings show that cardiac Nat2 expression is both
      temporally and spatially regulated during development. In neonatal mice, cardiac
      Nat2 expression is most extensive in the central fibrous body and is evident in
      the atrioventricular valves and the valves of the great vessels. Whereas Nat2
      expression is not detected in ventricular myocardial cells, Nat2 is strongly
      expressed in scattered cells in the region of the sinus node, the epicardium of
      the right atrial appendage, and in the pulmonary artery. Expression of active
      NAT2 protein is maximal when the developing heart attains the adult circulation
      pattern and moves from metabolizing glucose to fatty acids. NAT2 acetylating
      activity in cardiac tissue from Nat2(-/-) and Nat2(+/-) mice indicates a lack of
      compensating acetylating activity either from other acetylating enzymes or by
      NAT2 encoded by the wild-type Nat2 allele in Nat2(+/-) heterozygotes. The
      temporal and spatial control of murine Nat2 expression points to an endogenous
      role distinct from xenobiotic metabolism and indicates that Nat2 expression may
      be useful as a marker in cardiac development.

PMID- 15872052
TI  - Histological analysis of GFP expression in murine bone.
AB  - The power for appreciating complex cellular interactions during embryonic
      development using green fluorescent protein (GFP) as a visual histological marker
      has not been applied to adult tissues due to loss of GFP signal during paraffin
      embedding and a high autofluorescent background, particularly in section of bone
      and bone marrow. Here we demonstrate that the GFP signal is well preserved in
      frozen sections of adult decalcified bone. Using a tape-transfer system that
      preserves histological relationships, GFP expression can be related to standard
      histological stains used in bone biology research. The choice of a dual-filter
      cube and a strong GFP signal makes it possible to readily distinguish at least
      four different GFP colors that are distinctly different from the autofluorescent
      background. An additional advantage of the frozen sections is better preservation
      of immunological epitopes that allow colocalization of an immunostained section
      with an endogenous GFP and a strong lacZ signal emanating from a beta-gal marker
      gene. We present an approach for recording multiple images from the same
      histological section that allows colocalization of a GFP signal with subsequent
      stains and procedures that destroy GFP. Examples that illustrate the flexibility
      for dual imaging of various fluorescent signals are described in this study. The
      same imaging approach can serve as a vehicle for archiving, retrieving, and
      sharing histological images among research groups.

PMID- 15872053
TI  - Attenuation of accumulation of neointimal lipid by pioglitazone in mice
      genetically deficient in insulin receptor substrate-2 and apolipoprotein E.
AB  - Rupture of vulnerable atherosclerotic plaques that are characterized by extensive
      neointimal accumulation of lipid is a cause of acute coronary syndromes. To
      identify whether insulin resistance alters atherogenesis, we characterized the
      composition of atherosclerotic lesions in the proximal aortas in mice deficient
      in apolipoprotein E (ApoE(-/-)) and in ApoE(-/-) mice in which insulin resistance
      was intensified by a concomitant heterozygous deficiency in insulin receptor
      substrate type 2 (IRS2(+/-) ApoE(-/-) mice). In addition, we characterized the
      effect of an insulin sensitizer, pioglitazone, on the atherogenesis in IRS2(+/-)
      ApoE(-/-) mice. The extent of the aortic intima occupied by lesion was increased
      in the IRS2(+/-) ApoE(-/-) compared with ApoE(-/-) mice (79 +/- 3% compared with
      68 +/- 8%, p<0.05). Treatment with pioglitazone decreased the neointimal content
      of lipid in 20-week-old mice from 50 +/- 6% to 30 +/- 7%, p=0.005 and decreased
      the cellularity reflected by the multisection cross-sectional areas of lesions
      comprising cells in atheroma from 24 +/- 1% to 19 +/- 3%, p=0.018. Accordingly,
      genetically induced intensification of insulin resistance increases atheroma
      formation. Furthermore, attenuation of insulin resistance by treatment with
      pioglitazone decreases accumulation of lipid in the neointima.

PMID- 15872054
TI  - HLA-DR- and CD11c-positive dendritic cells penetrate beyond well-developed
      epithelial tight junctions in human nasal mucosa of allergic rhinitis.
AB  - The epithelial barrier of the upper respiratory tract plays a crucial role in
      host defense. In this study, to elucidate whether there is antigen monitoring by
      dendritic cells (DCs) beyond the epithelial tight-junction barrier in allergic
      rhinitis, we investigated the expression and function of tight junctions and
      characterized DCs in the epithelium of nasal mucosa from patients with allergic
      rhinitis. In reverse transcription-polymerase chain reaction, mRNAs of tight
      junction proteins occludin, JAM-1, ZO-1, and claudin-1, -4, -7, -8, -12, -13, and
      -14 were detected in the nasal mucosa. Occludin, JAM-1, and ZO-1 were colocalized
      in the uppermost layer in the pseudostratified epithelium of the nasal mucosa,
      whereas claudin-1, -4, and -7 were found throughout the epithelium. In freeze
      fracture replicas of the nasal mucosa, continuous tight-junction strands formed
      well-developed networks. Epithelial barrier function measured by a dye tracer was
      well maintained in occludin-positive tight junctions in the epithelium of the
      nasal mucosa. HLA-DR- and CD11c-positive DCs expressed claudin-1 and penetrated
      beyond occludin in the epithelium of the nasal mucosa with, but not without,
      allergic rhinitis. These results indicate that DCs may easily access antigens
      beyond epithelial tight junctions in the human nasal mucosa of allergic rhinitis.

PMID- 15872055
TI  - BRCA1 gene expression in breast cancer: a correlative study between real-time RT
      PCR and immunohistochemistry.
AB  - Breast cancer is a major cause of cancer-related mortality in women. There are
      major discrepancies concerning the usefulness of various antibodies in detecting
      breast cancer susceptibility gene 1 (BRCA1) protein and its subcellular
      localization. The aim of the present study was to determine the specificity and
      sensitivity of immunohistochemistry (IHC) as a screening method for demonstrating
      BRCA1 expression. BRCA1 gene expression in archival paraffin-embedded breast
      cancer tissues was studied simultaneously at the protein and mRNA levels, and the
      two findings were compared. Forty-eight archival paraffin-embedded breast cancer
      tissues were studied for BRCA1 gene expression at protein level by IHC using four
      different antibodies against different BRCA1 epitopes and at mRNA level using
      real-time RT-PCR. BRCA1 mRNA expression was reduced or absent in 79% of the
      samples, and this finding correlated significantly with loss of BRCA1 protein
      expression in 83% of breast cancer tissues using one BRCA1 antibody studied (AB
      1, against N-terminus epitope). The specificity of this antibody was 91.3%, and
      its sensitivity was 66.6%. There was no significant correlation between BRCA1
      mRNA and protein expression as demonstrated by the remaining three antibodies.
      Antibody 8F7 had the highest sensitivity of 100%, but its specificity was 30.4%
      if mRNA levels were considered as the reference standard.

PMID- 15872056
TI  - Ex vivo modeling of oral HIV transmission in human palatine tonsil.
AB  - The majority of newly acquired HIV infections are believed to occur following
      transmission of virus infectivity across mucosal surfaces, although many
      mechanistic details still remain unresolved. We have used human ex vivo organ
      cultures and primary cell populations to analyze the cellular and molecular basis
      for mucosal HIV transmission. By using human palatine tonsil from routine
      tonsillectomies and semen from HIV-positive donors, we have created an
      experimental equivalent to oral HIV transmission. HIV infection was readily
      transferred into tonsillar lymphocytes, but this transmission into lymphocytes
      was dramatically reduced when the exposed lymphocyte populations were protected
      by intact mucosal surfaces. In this study, we consider the impact that leukocyte
      activation and morphological aberrations in surface structure may have on
      susceptibility to primary HIV infection and introduce novel time-lapse confocal
      microscopy procedures that begin to reveal the dynamic complexity associated with
      cell-mediated HIV transmission.

PMID- 15872057
TI  - Presence of anti-cystatin C-positive dendritic cells or macrophages and
      localization of cysteine proteases in the apical bud of the enamel organ in the
      rat incisor.
AB  - Cystatin C, a cysteine protease inhibitor, was examined in the apical buds of rat
      incisors by immunohistochemistry, because in transition and maturation zones most
      of the dendritic cells in the papillary layer are anti-cystatin C-positive. Anti
      cystatin C-labeled cells were sparse and localized to the proliferation and
      differentiation zones, constituting the apical bud of 5-week-old rat incisors.
      These cells were considered macrophages or dendritic cells, based on their
      reactivity with OX6 and ED1, as well as their ultrastructure. Basement membrane
      at the periphery of apical bud was also labeled by anti-cystatin C antibody. The
      apical buds included a few apoptotic fragments and weak reactivity with antibody
      to cathepsin L, a cysteine protease. Reactivity to anti-cystatin C and anti
      cathepsin L antibodies was also detected in the apical bud of newborn rat
      incisors. These results suggest that the cystatin C-positive macrophages or
      dendritic cells are involved in normal incisor formation. They may be related to
      the clearance of apoptotic cells or protection from putative cysteine protease
      activity.

PMID- 15872058
TI  - Chondrogenic potential of mouse calvarial mesenchyme.
AB  - Facial and calvarial bones form intramembranously without a cartilagenous model;
      however, cultured chick calvarial mesenchyme cells may differentiate into both
      osteoblasts and chondroblasts and, in rodents, small cartilages occasionally form
      at the sutures in vivo. Therefore, we wanted to investigate what factors regulate
      normal differentiation of calvarial mesenchymal cells directly into osteoblasts.
      In embryonic mouse heads and in cultured tissue explants, we analyzed the
      expression of selected transcription factors and extracellular matrix molecules
      associated with bone and cartilage development. Cartilage markers Sox9 and type
      II collagen were expressed in all craniofacial cartilages. In addition, Msx2 and
      type I collagen were expressed in sense capsule cartilages. We also observed that
      the undifferentiated calvarial mesenchyme and the osteogenic fronts in the jaw
      expressed Col2A1. Moreover, we found that cultured mouse calvarial mesenchyme
      could develop into cartilage. Of the 49 explants that contained mesenchyme,
      intramembranous ossification occurred in 35%. Only cartilage formed in 4%, and
      both cartilage and bone formed in 4%. Our study confirms that calvarial
      mesenchyme, which normally gives rise to intramembranous bone, also has
      chondrogenic potential.

PMID- 15872059
TI  - Functional dissociation of the basolateral transcytotic compartment from the
      apical phago-lysosomal compartment in human osteoclasts.
AB  - Tartrate-resistant acid phosphatase (TRAP) is essential for elimination of
      Staphylococcus aureus, the main infectious agent responsible for osteomyelitis.
      This in vitro study investigated uptake and processing of fluorescence-labeled S.
      aureus by human osteoclasts and dendritic cells. The cells were stained for TRAP
      and the acidic compartment using a fluorescence-based protocol. In dendritic
      cells, TRAP and bacteria were colocalized. In osteoclasts, there was no
      colocalization of bacteria, TRAP, or the acidic compartment, indicating that
      there are three distinct vesicular compartments: the apical phago-lysosomal
      compartment, the basal secretory compartment, and the basolateral transcytotic
      compartment. Dissociation of the TRAP-containing transcytotic vesicles from the
      apical phago-lysosomal compartment may restrain osteoclasts from eliminating S.
      aureus.

PMID- 15872060
TI  - 5-Hydroxytryptamine (5HT) receptors in the heart valves of cynomolgus monkeys and
      Sprague-Dawley rats.
AB  - 5-Hydroxytryptamine-2B receptor (5HT2BR) stimulation is known to cause fibroblast
      mitogenesis, and the mitogenic effect has been proposed to trigger valvular heart
      disease in humans. In this study, we used real-time polymerase chain reaction
      (TaqMan) to quantify transcript levels of 5HT2B, 5HT2C, and 5HT1B receptors and
      immunohistochemistry (IHC) to detect the tissue localization of these receptors
      in the normal heart valves of cynomolgus (CM) monkeys and Sprague-Dawley (S-D)
      rats. In both species, positive immunostaining was noted for 5HT1B and 5HT2B
      receptors in mitral, tricuspid, aortic, and pulmonary valves, and the cell types
      showing positive staining were interstitial cells and endothelial cells lining
      the valve leaflet. In CM monkeys, 5HT2CR was expressed only in the endothelial
      cells lining the leaflet, whereas S-D valves were negative for this receptor. IHC
      results were correlated with 5HT2B and 5HT1B receptor transcripts for all four
      valves. However, 5HT2C receptor transcripts were lower than 5HT2B or 5HT1B in all
      CM monkey valves, whereas 5HT2C transcripts were below the level of detection in
      any of the S-D rat valves. Our data showed the expression of 5HT2B, 5HT1B, and
      5HT2C receptors in the normal heart valves of CM monkeys and S-D rats, and IHC
      and TaqMan techniques may be used to study the potential mechanism of compounds
      with 5HT2BR agonist activity.

PMID- 15872061
TI  - Effect of low-frequency repetitive transcranial magnetic stimulation on
      interhemispheric inhibition.
AB  - We studied the effects of 1-Hz repetitive transcranial magnetic stimulation
      (rTMS) on the excitability of interhemispheric connections in 13 right-handed
      healthy volunteers. TMS was performed using figure-eight coils, and surface
      electromyography (EMG) was recorded from both first dorsal interosseous (FDI)
      muscles. A paired-pulse method with a conditioning stimulus (CS) to the motor
      cortex (M1) followed by a test stimulus to the opposite M1 was used to study the
      interhemispheric inhibition (ppIHI). Both CS and TS were adjusted to produce
      motor-evoked potentials of approximately 1 mV in the contralateral FDI muscles.
      After baseline measurement of right-to-left IHI (pre-RIHI) and left-to-right IHI
      (pre-LIHI), rTMS was applied over left M1 at 1 Hz with 900 stimuli at 115% of
      resting motor threshold. After rTMS, ppIHI was studied using both the pre-rTMS CS
      (post-RIHI and post-LIHI) and an adjusted post-rTMS CS set to produce 1-mV motor
      evoked potentials (MEPs; post-RIHI(adj) and post-LIHI(adj)). The TS was set to
      produce 1-mV MEPs. There was a significant reduction in post-LIHI (P = 0.0049)
      and post-LIHI(adj) (P = 0.0169) compared with pre-LIHI at both interstimulus
      intervals of 10 and 40 ms. Post-RIHI was significantly reduced compared with pre
      RIHI (P = 0.0015) but pre-RIHI and post-RIHI(adj) were not significantly
      different. We conclude that 1-Hz rTMS reduces IHI in both directions but is
      predominantly from the stimulated to the unstimulated hemisphere. Low-frequency
      rTMS may be used to modulate the excitability of IHI circuits. Treatment
      protocols using low-frequency rTMS to reduce cortical excitability in
      neurological and psychiatric conditions need to take into account their effects
      on IHI.

PMID- 15872062
TI  - Dissociation of sensorimotor deficits after rostral versus caudal lesions in the
      primary motor cortex hand representation.
AB  - Primary motor cortex (M1) has traditionally been considered a motor structure.
      Although neurophysiologic studies have demonstrated that M1 is also influenced by
      somatosensory inputs (cutaneous and proprioceptive), the behavioral significance
      of these inputs has yet to be fully defined in primates. The present study
      describes differential sensory-related deficits after small ischemic lesions in
      either the rostral or caudal subregion of the M1 hand area in a nonhuman primate.
      Squirrel monkeys retrieved food pellets out of different sized wells drilled into
      a Plexiglas board. Before the lesion, monkeys retrieved pellets by directing the
      hand to the well, inserting fingers directly into it, and extracting the pellet.
      After a lesion to the rostral portion of M1, monkeys frequently failed to direct
      the hand accurately to the well. Instead, fingers contacted the surface of the
      board outside the well before entering the well. These aiming errors are
      consistent with both the large amount of proximal motor outputs and the
      predominant proprioceptive inputs of rostral M1. Overall, these aiming errors are
      suggestive of dysfunctional processing of proprioceptive information or the
      failure to integrate proprioceptive information with motor commands. In contrast,
      after a lesion to the caudal portion of M1, monkeys frequently examined their
      palm visually for the presence of the pellet after an attempted retrieval. These
      errors are consistent with both the large amount of distal motor outputs and the
      predominant cutaneous inputs of caudal M1. Thus these errors are suggestive of a
      deficit in processing of cutaneous information or the failure to integrate
      cutaneous information with motor commands. Rostral and caudal M1 lesions result
      in different deficits in sensory-dependent motor control that appear to correlate
      with broad segregation of motor outputs and previously described sensory inputs
      of M1.

PMID- 15872063
TI  - Orientation tuning, but not direction selectivity, is invariant to temporal
      frequency in primary visual cortex.
AB  - The activity of neurons in primary visual cortex is influenced by the
      orientation, contrast, and temporal frequency of a visual stimulus. This raises
      the question of how these stimulus properties interact to shape neuronal
      responses. While past studies have shown that the bandwidth of orientation tuning
      is invariant to stimulus contrast, the influence of temporal frequency on
      orientation-tuning bandwidth is unknown. Here, we investigate the influence of
      temporal frequency on orientation tuning and direction selectivity in area 17 of
      ferret visual cortex. For both simple cells and complex cells, measures of
      orientation-tuning bandwidth (half-width at half-maximum response) are
      approximately 20-25 degrees across a wide range of temporal frequencies. Thus
      cortical neurons display temporal-frequency invariant orientation tuning. In
      contrast, direction selectivity is typically reduced, and occasionally reverses,
      at nonpreferred temporal frequencies. These results show that the mechanisms
      contributing to the generation of orientation tuning and direction selectivity
      are differentially affected by the temporal frequency of a visual stimulus and
      support the notion that stability of orientation tuning is an important aspect of
      visual processing.

PMID- 15872064
TI  - Drosophila CAKI/CMG protein, a homolog of human CASK, is essential for regulation
      of neurotransmitter vesicle release.
AB  - Vertebrate CASK is a member of the membrane-associated guanylate kinase (MAGUK)
      family of proteins. CASK is present in the nervous system where it binds to
      neurexin, a transmembrane protein localized in the presynaptic membrane. The
      Drosophila homologue of CASK is CAKI or CAMGUK. CAKI is expressed in the nervous
      system of larvae and adult flies. In adult flies, the expression of caki is
      particularly evident in the visual brain regions. To elucidate the functional
      role of CASK, we employed a caki null mutant in the model organism Drosophila
      melanogaster. By means of electrophysiological methods, we analyzed, in adult
      flies, the spontaneous and evoked neurotransmitter release at the neuromuscular
      junction (NMJ) as well as the functional status of the giant fiber pathway and of
      the visual system. We found that in caki mutants, when synaptic activity is
      modified, the spontaneous neurotransmitter release of the indirect flight muscle
      NMJ was increased, the response of the giant fiber pathway to continuous
      stimulation was impaired, and electroretinographic responses to single and
      continuous repetitive stimuli were altered and optomotor behavior was abnormal.
      These results support the involvement of CAKI in neurotransmitter release and
      nervous system function.

PMID- 15872065
TI  - Sulfhydryl oxidation reduces hippocampal susceptibility to hypoxia-induced
      spreading depression by activating BK channels.
AB  - The cytosolic redox status modulates ion channels and receptors by
      oxidizing/reducing their sulfhydryl (SH) groups. We therefore analyzed to what
      degree SH modulation affects hippocampal susceptibility to hypoxia. In rat
      hippocampal slices, severe hypoxia caused a massive depolarization of CA1 neurons
      and a negative shift of the extracellular DC potential, the characteristic sign
      of hypoxia-induced spreading depression (HSD). Oxidizing SH groups by 5,5'
      dithiobis 2-nitrobenzoic acid (DTNB, 2 mM) postponed HSD by 30%, whereas their
      reduction by 1,4-dithio-dl-threitol (DTT, 2 mM) or alkylation by N-ethylmaleimide
      (500 microM) hastened HSD onset. The DTNB-induced postponement of HSD was not
      affected by tolbutamide (200 microM), dl-2-amino-5-phosphonovaleric acid (150
      microM), or 6-cyano-7-nitroquinoxaline-2,3-dione (25 microM). It was abolished,
      however, by Ni2+ (2 mM), withdrawal of extracellular Ca2+, charybdotoxin (25 nM),
      and iberiotoxin (50 nM). In CA1 neurons DTNB induced a moderate
      hyperpolarization, blocked spontaneous spike discharges and postponed the massive
      hypoxic depolarization. DTT induced burst firing, depolarized glial cells, and
      hastened the onset of the massive hypoxic depolarization. Schaffer-collateral/CA1
      synapses were blocked by DTT but not by DTNB; axonal conduction remained intact.
      Mitochondria did not markedly respond to DTNB or DTT. While the targets of DTT
      are less clear, the postponement of HSD by DTNB indicates that sulfhydryl
      oxidation increases the tolerance of hippocampal tissue slices against hypoxia.
      We identified as the underlying mechanism the activation of BK channels in a
      Ca(2+)-sensitive manner. Accordingly, ionic disregulation and the loss of
      membrane potential occur later or might even be prevented during short-term
      insults. Therefore well-directed oxidation of SH groups could mediate
      neuroprotection.

PMID- 15872066
TI  - Deletions of rhythmic motoneuron activity during fictive locomotion and scratch
      provide clues to the organization of the mammalian central pattern generator.
AB  - We examined the features of spontaneous deletions of bursts of motoneuron
      activity that can occur within otherwise rhythmic alternating flexor and extensor
      activity during fictive locomotion and scratch in adult decerebrate cats.
      Deletions of activity were observed both in hindlimb flexor and extensor
      motoneuron pools during brain stem-stimulation-evoked fictive locomotion but only
      in extensors during fictive scratch. Paired intracellular motoneuron recordings
      showed that deletions reduced the depolarization of homonymous motoneurons in
      qualitatively similar ways. Differences occurred in the extent to which activity
      in synergist motoneuron pools operating at other joints within the limb was
      reduced during deletions. The timing of the rhythmic activity that followed a
      deletion was often at an integer multiple of the preexisting locomotor or scratch
      cycle period. This maintenance of cycle period was also seen during deletions in
      which there was a complete failure of motoneuron depolarization. The activity of
      antagonist motoneurons was usually sustained during deletions with some rhythmic
      modulation at intervals of the preexisting cycle period. We discuss an
      organization of the central pattern generator for locomotion and scratch that
      functions as a single rhythm generator with separate and multiple pattern
      formation modules for controlling the hyper- and depolarization of subsets of
      motoneurons within the limb.

PMID- 15872067
TI  - Discharge properties of MST neurons that project to the frontal pursuit area in
      macaque monkeys.
AB  - We have used antidromic activation to determine the functional discharge
      properties of neurons that project to the frontal pursuit area (FPA) from the
      medial-superior temporal visual area (MST). In awake rhesus monkeys, MST neurons
      were considered to be activated antidromically if they emitted action potentials
      at fixed, short latencies after stimulation in the FPA and if the activation
      passed the collision test. Antidromically activated neurons (n = 37) and a sample
      of the overall population of MST neurons (n = 110) then were studied during
      pursuit eye movements across a dark background and during laminar motion of a
      large random-dot texture and optic flow expansion and contraction during
      fixation. Antidromically activated neurons showed direction tuning during pursuit
      (25/37), during laminar image motion (21/37), or both (16/37). Of 27 neurons
      tested with optic flow stimuli, 14 showed tuning for optic flow expansion (n =
      10) or contraction (n = 4). There were no statistically significant differences
      in the response properties of the antidromically activated and control samples.
      Preferred directions for pursuit and laminar image motion did not show any
      statistically significant biases, and the preferred directions for eye versus
      image motion in each sample tended to be equally divided between aligned and
      opposed. There were small differences between the control and antidromically
      activated populations in preferred speeds for laminar motion and optic flow;
      these might have reached statistical significance with larger samples of
      antidromically activated neurons. We conclude that the population of MST neurons
      projecting to the FPA is highly diverse and quite similar to the general
      population of neurons in MST.

PMID- 15872068
TI  - Stimulation of the parapyramidal region of the neonatal rat brain stem produces
      locomotor-like activity involving spinal 5-HT7 and 5-HT2A receptors.
AB  - Locomotion can be induced in rodents by direct application 5-hydroxytryptamine (5
      HT) onto the spinal cord. Previous studies suggest important roles for 5-HT7 and
      5-HT2A receptors in the locomotor effects of 5-HT. Here we show for the first
      time that activation of a discrete population of 5-HT neurons in the rodent brain
      stem produces locomotion and that the evoked locomotion requires 5-HT7 and 5-HT2A
      receptors. Cells localized in the parapyramidal region (PPR) of the mid-medulla
      produced locomotor-like activity as a result of either electrical or chemical
      stimulation, and PPR-evoked locomotor-like activity was blocked by antagonists to
      5-HT2A and 5-HT7 receptors located on separate populations of neurons
      concentrated in different rostro-caudal regions. 5-HT7 receptor antagonists
      blocked locomotor-like activity when applied above the L3 segment; 5-HT2A
      receptor antagonists blocked locomotor-like activity only when applied below the
      L2 segment. 5-HT7 receptor antagonists decreased step cycle duration, consistent
      with an action on neurons involved in the rhythm-generating function of the
      central pattern generator (CPG) for locomotion. 5-HT2A antagonists reduced the
      amplitude of ventral root activity with only small effects on step cycle
      duration, suggesting an action directly on cells involved in the output stage of
      the pattern generator for locomotion, including motoneurons and premotor cells.
      Experiments with selective antagonists show that dopaminergic (D1, D2) and
      noradrenergic (alpha1, alpha2) receptors are not critical for PPR-evoked
      locomotor-like activity.

PMID- 15872069
TI  - Spike timing in CA3 pyramidal cells during behavior: implications for synaptic
      transmission.
AB  - Spike timing is thought to be an important mechanism for transmitting information
      in the CNS. Recent studies have emphasized millisecond precision in spike timing
      to allow temporal summation of rapid synaptic signals. However, spike timing over
      slower time scales could also be important, through mechanisms including activity
      dependent synaptic plasticity or temporal summation of slow postsynaptic
      potentials (PSPs) such as those mediated by kainate receptors. To determine the
      extent to which these slower mechanisms contribute to information processing, it
      is first necessary to understand the properties of behaviorally relevant spike
      timing over this slow time scale. In this study, we examine the activity of CA3
      pyramidal cells during the performance of a complex behavioral task in rats.
      Sustained firing rates vary over a wide range, and the firing rate of a cell is
      poorly correlated with the behavioral cues to which the cell responds. Nonrandom
      interactions between successive spikes can last for several seconds, but the
      nonrandom distribution of interspike intervals (ISIs) can account for the
      majority of nonrandom multi-spike patterns. During a stimulus, cellular responses
      are temporally complex, causing a shift in spike timing that favors intermediate
      ISIs over short and long ISIs. Response discrimination between related stimuli
      occurs through changes in both response time-course and response intensity.
      Precise synchrony between cells is limited, but loosely correlated firing between
      cells is common. This study indicates that spike timing is regulated over long
      time scales and suggests that slow synaptic mechanisms could play a substantial
      role in information processing in the CNS.

PMID- 15872070
TI  - Role for calcium signaling and arachidonic acid metabolites in the activity
      dependent increase of AHP amplitude in leech T sensory neurons.
AB  - Previous studies have revealed a new form of activity-dependent modulation of the
      afterhyperpolarization (AHP) in tactile (T) neurons of the leech Hirudo
      medicinalis. The firing of T cells is characterized by an AHP, which is mainly
      due to the activity of the Na+/K+ ATPase. Low-frequency repetitive stimulation of
      T neurons leads to a robust increment of the AHP amplitude, which is correlated
      with a synaptic depression between T neuron and follower cells. In the present
      study, we explored the molecular cascades underlying the AHP increase. We tested
      the hypothesis that this activity-dependent phenomenon was triggered by calcium
      influx during neural activity by applying blockers of voltage-dependent Ca2+
      channels. We report that AHP increase requires calcium influx that, in turn,
      induces release of calcium from intracellular stores so sustaining the
      enhancement of AHP. An elevation of the intracellular calcium can activate the
      cytosolic isoforms of the phosholipase A2 (PLA2). Therefore we analyzed the role
      of PLA2 in the increase of the AHP, and we provide evidence that not only PLA2
      but also the recruitment of arachidonic acid metabolites generated by the 5
      lipoxygenase pathway are necessary for the induction of AHP increase. These data
      indicate that a sophisticated cascade of intracellular signals links the
      repetitive discharge of T neurons to the activation of molecular pathways, which
      finally may alter the activity of critical enzymes such as the Na+/K+ ATPase,
      that sustains the generation of the AHP and its increase during repetitive
      stimulation. These results also suggest the potential importance of the poorly
      studied 5-lipoxygenase pathway in forms of neuronal plasticity.

PMID- 15872071
TI  - Optical imaging of large-scale correlated wave activity in the developing rat
      CNS.
AB  - Correlated neuronal activity plays a fundamental role in the development of the
      nervous system. Using a multiple-site optical recording technique with a fast
      voltage-sensitive dye, we previously reported a novel form of correlated activity
      in the chick embryo, which showed wide propagation throughout the CNS. In this
      study, we report that similar wave activity is generated in the embryonic rat
      CNS. Electrical stimulation applied to the cervical cord evoked wave activity
      that traveled over a wide region of the CNS including the medulla, pons,
      midbrain, diencephalon, and spinal cord. Small signals were also detected from
      the cerebellum and part of the cerebrum. Stimulation applied to the cranial
      nerves such as the trigeminal and vagus nerves evoked waves with similar
      patterns, indicating that the wave is triggered by external sensory inputs. This
      wave activity was inhibited by glutamate-, acetylcholine-, GABA- and glycine
      receptor antagonists in addition to gap junction blockers such as octanol and
      18beta-glycyrrhetinic acid. In the immunohistochemical study, significant
      immunoreactivity of connexin26 and connexin32 was also observed. Wave activity
      detected with a voltage-sensitive dye was accompanied by a Ca(2+)-wave,
      indicating that it not only provides electrical synchrony but also biochemical
      signals associated with [Ca2+](i) elevation. These characteristics of the wave
      activity are similar to those of the depolarization wave reported in the chick
      embryo, suggesting that the large-scale depolarization wave is globally generated
      across different species.

PMID- 15872072
TI  - Immediate changes in anticipatory activity of caudate neurons associated with
      reversal of position-reward contingency.
AB  - The primate caudate nucleus plays a crucial role in transforming
      cognitive/motivational information into eye movement signals. A subset of caudate
      projection neurons fire before a visual target's onset. This anticipatory
      activity is sensitive to position-reward contingencies and correlates with
      saccade latency, which is shorter toward a rewarded position. We recorded single
      unit activity of caudate projection neurons to examine the dynamics of change in
      anticipatory activity immediately after switches of the position-reward
      contingency. Two monkeys performed a visually guided saccade task where only one
      position was associated with reward. The position-reward mapping remained
      constant within a block, but was reversed frequently between blocks without any
      indication to the monkey. Therefore the switch could be detected only by
      unexpected reward delivery or unexpected lack of reward. After the switch, both
      saccade latency and anticipatory activity showed reliable changes already in the
      second trial, whether or not the first trial was rewarded. However, anticipatory
      activity in the second trial was generally higher if the first trial was
      rewarded, and the measured saccade latencies could be better explained by the
      difference in anticipatory activity between the two caudate nuclei. We suggest
      that anticipatory activity of caudate neurons reflects the reversal set of reward
      position contingency.

PMID- 15872073
TI  - Formation and phosphorylation of the PINCH-1-integrin linked kinase-alpha-parvin
      complex are important for regulation of renal glomerular podocyte adhesion,
      architecture, and survival.
AB  - Alterations in the cellular architecture, adhesion, and/or loss of glomerular
      podocytes are causal factors in the development of proteinuria and the
      progression to end-stage renal failure. With the use of an inducible podocyte
      differentiation system, it was found that the cellular levels of PINCH-1,
      integrin linked kinase (ILK), and alpha-parvin, cytoplasmic components of cell
      extracellular matrix adhesions, were significantly increased during podocyte
      differentiation. Concomitantly, an increased amount of the PINCH-1-ILK-alpha
      parvin complex was detected in the differentiated, foot process-containing
      podocytes. Overexpression of the PINCH-1-binding ankyrin repeat domain of ILK but
      not that of a PINCH-1-binding defective mutant form of the ankyrin domain
      effectively inhibited the formation of the PINCH-1-ILK-alpha-parvin complex.
      Disruption of the PINCH-1-ILK-alpha-parvin complex significantly reduced the
      podocyte-matrix adhesion and foot process formation. Furthermore, a marked
      increase of apoptosis in the podocytes in which the assembly of the PINCH-1-ILK
      alpha-parvin complex was compromised was detected. Inhibition of ILK with a small
      compound inhibitor also altered podocyte cytoskeleton and increased apoptosis.
      Finally, it is shown that alpha-parvin is phosphorylated in podocytes. Mutations
      at the alpha-parvin N-terminal proline-directed serine phosphorylation sites
      reduced its complex formation with ILK and resulted in defects in podocyte
      adhesion, architecture, and survival. These results provide important evidence
      for a crucial role of the PINCH-1-ILK-alpha-parvin complex in the control of
      podocyte adhesion, morphology, and survival.

PMID- 15872074
TI  - Endothelin-induced increased aldosterone activity mediates augmented distal
      nephron acidification as a result of dietary protein.
AB  - The hypothesis that increased dietary protein augments distal nephron
      acidification through endothelin-mediated increased aldosterone activity was
      tested. Munich-Wistar rats were studied after 3 wk of diets with 50% high protein
      (HiPro) and 20% control (CON) casein-provided protein, the latter comparable to
      standard diet. HiPro versus CON rats had higher distal nephron H+ secretion by in
      vivo microperfusion as shown previously. Perfusion with inhibitors of Na+/H+
      exchange (EIPA, 10(-5) M), H+-ATPase (bafilomycin, 10(-7) M), and H+-K+-ATPase
      (Sch 28080 [10(-5) M] and ouabain [10(-3) M]) support that higher Na+/H+ exchange
      and higher H+-ATPase but not higher H+-K+-ATPase activity mediated increased H+
      secretion in HiPro rats. Oral bosentan, an endothelin A/B receptor antagonist,
      decreased distal nephron H+ secretion in HiPro rats as a result of reduced Na+/H+
      exchange and H+-ATPase activity as shown previously by the authors' laboratory.
      HiPro versus CON rats had higher plasma aldosterone (60.9 +/- 5.9 versus 42.2 +/-
      4.4 pg/ml; P < 0.024) and higher urine aldosterone excretion (21.9 +/- 3.9 versus
      10.5 +/- 2.8 ng/d; P < 0.04) in the absence but not presence of bosentan,
      consistent with endothelin-mediated increased aldosterone secretion. HiPro rats
      that did versus did not ingest the aldosterone antagonist spironolactone had
      lower distal nephron H+ secretion (29.2 +/- 3.3 versus 42.1 +/- 3.8 pmol/mm per
      min; P < 0.05) as a result of lower H+-ATPase activity without differences in
      Na+/H+ exchange or H+-K+-ATPase activity. The data support that dietary protein
      provided as casein increases distal nephron acidification through endothelin
      stimulated Na+/H+ exchange and endothelin-stimulated aldosterone secretion that
      increases H+-ATPase activity.

PMID- 15872075
TI  - Detection and localization of proteinuria by dynamic contrast-enhanced magnetic
      resonance imaging using MS325.
AB  - After renal transplantation, persistent glomerular disease affecting the native
      kidneys typically causes albuminuria, at least for a period of time, making it
      difficult to determine in a noninvasive fashion whether proteinuria originates in
      the native kidneys or the renal allograft. To address this problem, dynamic
      contrast-enhanced magnetic resonance imaging (MRI) using gadolinium (Gd)-based
      albumin-bound blood pool contrast agent (MS325) to localize proteinuria was
      investigated. Glomerular proteinuria was induced in Sprague-Dawley rats by
      intravenous injection of puromycin aminonucleoside (PAN), whereas control rats
      received physiologic saline vehicle. Both groups of animals underwent a 40-min
      dynamic contrast-enhanced MRI using radio frequency spoiled gradient echo imaging
      sequence after injection of Gd-labeled MS325. Contrast uptake and clearance
      curves for cortex and medulla were determined from acquired MR images. Compared
      with controls, proteinuric rats exhibited significantly lower elimination rate
      constants. The use of gadopentetate dimeglumine (Gd-DTPA) as a contrast agent
      showed smaller and less specific differences between proteinuric and control
      groups. In rats with one proteinuric kidney (PAN-treated) and one normal kidney
      (transplanted from a normal rat), MRI using MS325 was able to differentiate
      between the two kidneys. The results suggest that MRI with an albumin-bound blood
      pool contrast agent may be a useful noninvasive way to localize proteinuria. If
      this technique can be successfully applied in human patients, it may allow for
      the localization of proteinuria after kidney transplant and thereby provide a
      noninvasive way to detect disease affecting the renal allograft.

PMID- 15872076
TI  - Relationship between albuminuria and cardiovascular disease in Type 2 diabetes.
AB  - Impaired renal function and albuminuria, common among people with type 2
      diabetes, are strong predictors of atherosclerotic cardiovascular events.
      However, the relationships among albuminuria and measures of calcified
      atherosclerotic plaque are unknown. Coronary and carotid artery calcified plaque
      were measured using fast-gated helical computed tomography, and B-mode
      ultrasonography measured common carotid artery intima-medial thickness (IMT) in
      588 white participants with type 2 diabetes from 325 families ascertained for the
      presence of multiple siblings with type 2 diabetes. Measured risk factors
      included age, gender, BP, body mass index, GFR, glycosylated hemoglobin, LDL
      cholesterol, HDL cholesterol, smoking, and medications that affect urine
      albumin:creatinine ratio (ACR). Generalized estimating equations with
      exchangeable correlation and the sandwich estimator of the variance were used to
      test for an association among coronary artery calcified plaque, carotid artery
      calcified plaque, carotid IMT, and ACR while adjusting for measured risk factors.
      Participants had a mean +/- SD (median) age of 61.2 +/- 9.2 yr (61.0 yr), ACR of
      106.2 +/- 590 mg/g (12.9 mg/g), GFR of 93.3 +/- 33.2 ml/min (87.4 ml/min),
      coronary artery calcium mass score of 1394 +/- 2685 (323), carotid artery calcium
      mass score of 295 +/- 652 (51), and IMT of 0.66 +/- 0.12 mm (0.65 mm). Adjusting
      for the measured covariates, ACR was strongly and positively associated with
      coronary artery calcium (P = 0.004) and carotid artery calcium (P = 0.0004).
      Albuminuria is strongly associated with calcified plaque in the coronary and
      carotid arteries in white individuals with type 2 diabetes and relatively
      preserved renal function.

PMID- 15872077
TI  - Nitric oxide upregulates induction of PDGF receptor-alpha expression in rat renal
      mesangial cells and in anti-Thy-1 glomerulonephritis.
AB  - PDGF and nitric oxide (NO) have been shown to participate in the progression of
      several forms of glomerulonephritis. A potential influence of NO on PDGF-mediated
      signaling cascades was therefore examined. Treatment of rat mesangial cells (MC)
      with the NO donors diethylenetriamine NO (DETA-NO) or spermine-NONOate resulted
      in a time- and dose-dependent upregulation of PDGF receptor alpha (PDGFRalpha)
      but not PDGFRbeta mRNA levels. Administration of DETA-NO also induced PDGFRalpha
      protein expression that was paralleled also by an enhanced receptor
      phosphorylation. Further experiments using 3-(5-hydroxymethyl-2-furyl)-1
      benzylindazole (YC-1), an activator of the soluble guanylyl cyclase (sGC), the
      membrane-soluble cyclic GMP (cGMP) analog 8-Bromo-PET-cGMP, and the inhibitors of
      sGC ODQ and NS2028 suggest that elevated cGMP levels are responsible for the
      effects of NO. Importantly, NO-dependent autophosphorylation of PDGFRalpha
      drastically augmented PDGF-AA-evoked phosphorylation of PKB/Akt, a classical
      downstream target of PDGFRalpha signaling. Furthermore, in a rat model of anti
      Thy-1 glomerulonephritis, expression and phosphorylation of PDGFRalpha but not
      PDGFRbeta expression was markedly reduced in nephritic animals that were treated
      with the inducible NO synthase inhibitor L-N6(1
      iminoethyl)lysine(dihydrochloride) (L-NIL) compared with non-L-NIL-treated
      nephritic rats as demonstrated by Western blotting and immunohistochemistry.
      Taken together, the data suggest that NO modulates PDGFRalpha-triggered signaling
      in a cGMP-dependent manner by induction of PDGFRalpha expression in MC and in a
      rat model of mesangioproliferative glomerulonephritis. The mechanistic details of
      this regulation have to be elucidated in further experiments.

PMID- 15872078
TI  - Importance of baseline distribution of proteinuria in renal outcomes trials:
      lessons from the reduction of endpoints in NIDDM with the angiotensin II
      antagonist losartan (RENAAL) study.
AB  - A key issue in the analysis of outcome trials is the adjustment for baseline
      covariates that influence the primary outcome. Imbalance of an important
      covariate between treatment groups at baseline is of considerable concern if one
      treatment group is favored over another with respect to the hypothesis testing
      outcome. With the use of the Reduction of Endpoints in NIDDM with the Angiotensin
      II Antagonist Losartan (RENAAL) study database as an example, the influence of
      baseline proteinuria on the primary composite endpoint, ESRD, and ESRD or death
      after adjusting for baseline proteinuria as a continuous covariate was examined.
      Increasing baseline proteinuria was associated with increased risk for renal
      events, confirming that proteinuria is an important covariate for renal outcomes.
      When the randomization was stratified according proteinuria <2000 mg/g or >/=2000
      mg/g, within the higher proteinuria stratum (>/=2000 mg/g), patients in the
      losartan group had a higher baseline mean proteinuria value. When the imbalance
      was adjusted, an increase in the magnitude and the significance of the risk
      reduction with losartan for each outcome was observed. No apparent interaction
      between treatment effect and baseline proteinuria was found, and there was no
      heterogeneity in the treatment response in patients with different baseline
      proteinuria levels. After proteinuria was adjusted as a continuous variable,
      greater treatment effects were observed in the RENAAL study. This effect was due
      solely to the imbalance in baseline proteinuria. Considering the importance of
      proteinuria as a risk factor, adjustment for baseline proteinuria as a continuous
      covariate should be prespecified in the design and analysis of clinical trials
      involving renal outcomes, even when patients are stratified on the basis of level
      of proteinuria.

PMID- 15872079
TI  - Integration of embryonic stem cells in metanephric kidney organ culture.
AB  - Many stages of nephrogenesis can be studied using cultured embryonic kidneys, but
      there is no efficient technique available to readily knockdown or overexpress
      transgenes for rapid evaluation of resulting phenotypes. Embryonic stem (ES)
      cells have unlimited developmental potential and can be manipulated at the
      molecular genetic level by a variety of methods. The aim of this study was to
      determine if ES cells could respond to developmental signals within the mouse
      embryonic day 12 to embryonic day 13 (E12 to E13) kidney microenvironment and
      incorporate into kidney structures. ROSA26 ES cells were shown to express beta
      galactosidase ubiquitously when cultured in the presence of leukemia inhibitory
      factor to suppress differentiation. When these cells were microinjected into E12
      to E13 metanephroi and then placed in transwell organ culture, ES cell-derived,
      beta-galactosidase-positive cells were identified in epithelial structures
      resembling tubules. On rare occasions, individual ES cells were observed in
      structures resembling glomerular tufts. Electron microscopy showed that the ES
      cell-derived tubules were surrounded by basement membrane and had apical
      microvilli and junctional complexes. Marker analysis revealed that a subset of
      these epithelial tubules bound Lotus tetragonolobus and expressed alpha(1)
      Na(+)/K(+) ATPase. ES cells were infected before injection with a cytomegalovirus
      promoter-green fluorescence protein (GFP) adenovirus and GFP expression was found
      as early as 18 h, persisting for up to 48 h in cultured kidneys. This ES cell
      technology may achieve the objective of obtaining a versatile cell culture system
      in which molecular interventions can be used in vitro and consequences of these
      perturbations on the normal kidney development program in vivo can be studied.

PMID- 15872080
TI  - Heparan sulfate of perlecan is involved in glomerular filtration.
AB  - Perlecan is a heparan sulfate proteoglycan and a major component of the
      glomerular basement membrane. To understand the role of heparan sulfate chains of
      perlecan in glomerular filtration, detailed analyses were performed of the
      kidneys of Hspg2(Delta)(3/)(Delta)(3) mice, whose perlecan lacks heparan sulfate
      attachment sites in N-terminal domain I. Macroscopic, histologic, and electron
      microscopic observations, as well as immunohistochemical and immunoelectron
      microscopic analyses using specific antibodies against perlecan and agrin core
      proteins, revealed no significant abnormalities in these mice under physiologic
      conditions. Polyethyleneimine staining demonstrated no significant changes in
      charge density in the glomerular basement membrane. Transcripts of other heparan
      sulfate proteoglycans, agrin, and collagen type XVIII, as well as perlecan, were
      expressed at similar levels to those in the wild-type littermates. Approximately
      40% of the perlecan synthesized by Hspg2(Delta)(3/)(Delta)(3) fibroblasts was
      substituted with heparin sulfate and 60% was substituted with chondroitin
      sulfate. All of the perlecan synthesized by wild-type fibroblasts contained
      heparin sulfate, indicating an altered substitution of glycosaminoglycans on
      Hspg2(Delta)(3/)(Delta)(3) perlecan. Immunostaining indicated that the level of
      chondroitin sulfate was actually increased in the Hspg2(Delta)(3/)(Delta)(3)
      glomerular basement membrane. When administered intraperitoneally with BSA,
      Hspg2(Delta)(3/)(Delta)(3) mice exhibited remarkable proteinuria. These findings
      suggest that heparan sulfate chains of perlecan play an important role in
      glomerular filtration, especially of a large amount of protein.

PMID- 15872081
TI  - CD40 ligand increases complement C3 secretion by proximal tubular epithelial
      cells.
AB  - Interstitial leukocyte infiltration is a major finding in tubulointerstitial
      damage (TID). Infiltrating lymphocytes interact with proximal tubular epithelial
      cells (PTEC) by means of secreted soluble factors and/or cell contact mechanisms.
      CD40 expressed onto PTEC can be engaged by CD40L present on T cells. PTEC are
      able to locally secrete complement C3, which may most likely promote TID. The aim
      of the study was to investigate the putative action of CD40 ligation on
      enhancement of C3 secretion by PTEC. Primary human PTEC and stabilized HK-2 cells
      were used in culture experiments. Cells were stimulated by soluble factors IL
      1beta, IFN-gamma, and/or CD40L-expressing murine fibroblast L cells. Analysis of
      C3 gene expression was evaluated by reverse-transcription PCR and Northern blot.
      Secreted C3 was assayed by ELISA and a functional hemolytic test on supernatants.
      Intracellular events were explored by the NF-kappaB-specific inhibitor caffeic
      acid phenetyl ester (CAPE). Among soluble factors, IL-1beta and IFN-gamma
      increased C3 gene expression and secretion (two-fold to three-fold versus basal)
      on both HK-2 and PTEC. CD40 engagement by CD40L upregulated HK-2 C3 secretion by
      four-fold. IL-1beta did not further increase CD40-induced C3 secretion, whereas
      IFN-gamma associated with CD40L was the strongest stimulus (30-fold increase).
      Inhibition of NF-kappaB offset CD40L-induced C3 secretion by 70%. CD40 ligation
      is able to enhance C3 secretion by PTEC. This cell contact mechanism is in
      synergism with a T cell-derived soluble factor (IFN-gamma). C3 secretion induced
      by CD40L may represent a mechanism of amplification of TID associated with
      lymphocyte infiltration.

PMID- 15872082
TI  - Beyond Framingham: cardiovascular risk profiling in ESRD.

PMID- 15872083
TI  - Linking metabolism and immunology: diabetic nephropathy is an inflammatory
      disease.

PMID- 15872084
TI  - The organization of the core proteins of the yeast spindle pole body.
AB  - The spindle pole body (SPB) is the microtubule organizing center of Saccharomyces
      cerevisiae. Its core includes the proteins Spc42, Spc110 (kendrin/pericentrin
      ortholog), calmodulin (Cmd1), Spc29, and Cnm67. Each was tagged with CFP and YFP
      and their proximity to each other was determined by fluorescence resonance energy
      transfer (FRET). FRET was measured by a new metric that accurately reflected the
      relative extent of energy transfer. The FRET values established the topology of
      the core proteins within the architecture of SPB. The N-termini of Spc42 and
      Spc29, and the C-termini of all the core proteins face the gap between the IL2
      layer and the central plaque. Spc110 traverses the central plaque and Cnm67 spans
      the IL2 layer. Spc42 is a central component of the central plaque where its N
      terminus is closely associated with the C-termini of Spc29, Cmd1, and Spc110.
      When the donor-acceptor pairs were ordered into five broad categories of
      increasing FRET, the ranking of the pairs specified a unique geometry for the
      positions of the core proteins, as shown by a mathematical proof. The geometry
      was integrated with prior cryoelectron tomography to create a model of the
      interwoven network of proteins within the central plaque. One prediction of the
      model, the dimerization of the calmodulin-binding domains of Spc110, was
      confirmed by in vitro analysis.

PMID- 15872085
TI  - Long-term self-renewal of postnatal muscle-derived stem cells.
AB  - The ability to undergo self-renewal is a defining characteristic of stem cells.
      Self-replenishing activity sustains tissue homeostasis and regeneration. In
      addition, stem cell therapy strategies require a heightened understanding of the
      basis of the self-renewal process to enable researchers and clinicians to obtain
      sufficient numbers of undifferentiated stem cells for cell and gene therapy.
      Here, we used postnatal muscle-derived stem cells to test the basic biological
      assumption of unlimited stem cell replication. Muscle-derived stem cells (MDSCs)
      expanded for 300 population doublings (PDs) showed no indication of replicative
      senescence. MDSCs preserved their phenotype (ScaI+/CD34+/desmin(low)) for 200 PDs
      and were capable of serial transplantation into the skeletal muscle of mdx mice,
      which model Duchenne muscular dystrophy. MDSCs expanded to this level exhibited
      high skeletal muscle regeneration comparable with that exhibited by minimally
      expanded cells. Expansion beyond 200 PDs resulted in lower muscle regeneration,
      loss of CD34 expression, loss of myogenic activity, and increased growth on soft
      agar, suggestive of inevitable cell aging attributable to expansion and possible
      transformation of the MDSCs. Although these results raise questions as to whether
      cellular transformations derive from cell culturing or provide evidence of cancer
      stem cells, they establish the remarkable long-term self-renewal and regeneration
      capacity of postnatal MDSCs.

PMID- 15872086
TI  - Calcium-induced human keratinocyte differentiation requires src- and fyn-mediated
      phosphatidylinositol 3-kinase-dependent activation of phospholipase C-gamma1.
AB  - We have previously demonstrated that phospholipase C (PLC)-gamma1 is required for
      calcium-induced human keratinocyte differentiation. In the present study, we
      investigated whether the activation of PLC-gamma1 by nonreceptor kinases such as
      src and fyn plays a role in mediating this process. Our results showed that the
      combination of dominant negative src and fyn blocked calcium-stimulated PLC
      gamma1 activity and human keratinocyte differentiation, whereas each separately
      has little effect. However, unlike the activation of PLC-gamma1 by epidermal
      growth factor, calcium-induced activation of PLC-gamma1 was not a result of
      direct tyrosine phosphorylation. Therefore, we examined an alternative mechanism,
      in particular phosphatidylinositol 3,4,5-triphosphate (PIP3) formed as a product
      of phosphatidylinositol 3-kinase (PI3K) activity. PIP3 binds to and activates PLC
      gamma1. The combination of dominant negative src and fyn blocked calcium-induced
      tyrosine phosphorylation of the regulatory subunit of PI3K, p85alpha, and the
      activity of the catalytic subunit of PI3K. PI3K inhibitors blocked calcium
      activation of PLC-gamma1 as well as the induction of keratinocyte differentiation
      markers involucrin and transglutaminase. These data indicate that calcium
      activates PLC-gamma1 via increased PIP3 formation mediated by c-src- and fyn
      activated PI3K. This activation is required for calcium-induced human
      keratinocyte differentiation.

PMID- 15872087
TI  - Structural and functional dissection of the Abp1 ADFH actin-binding domain
      reveals versatile in vivo adapter functions.
AB  - Abp1 is a multidomain protein that regulates the Arp2/3 complex and links
      proteins involved in endocytosis to the actin cytoskeleton. All of the proposed
      cellular functions of Abp1 involve actin filament binding, yet the actin binding
      site(s) on Abp1 have not been identified, nor has the importance of actin binding
      for Abp1 localization and function in vivo been tested. Here, we report the
      crystal structure of the Saccharomyces cerevisiae Abp1 actin-binding actin
      depolymerizing factor homology (ADFH) domain and dissect its activities by
      mutagenesis. Abp1-ADFH domain and ADF/cofilin structures are similar, and they
      use conserved surfaces to bind actin; however, there are also key differences
      that help explain their differential effects on actin dynamics. Using point
      mutations, we demonstrate that actin binding is required for localization of Abp1
      in vivo, the lethality caused by Abp1 overexpression, and the ability of Abp1 to
      activate Arp2/3 complex. Furthermore, we genetically uncouple ABP1 functions that
      overlap with SAC6, SLA1, and SLA2, showing they require distinct combinations of
      activities and interactions. Together, our data provide the first structural and
      functional view of the Abp1-actin interaction and show that Abp1 has distinct
      cellular roles as an adapter, linking different sets of ligands for each
      function.

PMID- 15872088
TI  - Synaptic clusters of MHC class II molecules induced on DCs by adhesion molecule
      mediated initial T-cell scanning.
AB  - Initial adhesive contacts between T lymphocytes and dendritic cells (DCs)
      facilitate recognition of peptide-MHC complexes by the TCR. In this report, we
      studied the dynamic behavior of adhesion and Ag receptors on DCs during initial
      contacts with T-cells. Adhesion molecules LFA-1- and ICAM-1,3-GFP as well as MHC
      class II-GFP molecules were very rapidly concentrated at the DC contact area.
      Binding of ICAM-3, and ICAM-1 to a lesser extent, to LFA-1 expressed by mature
      but not immature DC, induced MHC-II clustering into the immune synapse. Also,
      ICAM-3 binding to DC induced the activation of the Vav1-Rac1 axis, a regulatory
      pathway involved in actin cytoskeleton reorganization, which was essential for
      MHC-II clustering on DCs. Our results support a model in which ICAM-mediated MHC
      II clustering on DC constitutes a priming mechanism to enhance antigen
      presentation to T-cells.

PMID- 15872090
TI  - ACT-5 is an essential Caenorhabditis elegans actin required for intestinal
      microvilli formation.
AB  - Investigation of Caenorhabditis elegans act-5 gene function revealed that
      intestinal microvillus formation requires a specific actin isoform. ACT-5 is the
      most diverged of the five C. elegans actins, sharing only 93% identity with the
      other four. Green fluorescent protein reporter and immunofluorescence analysis
      indicated that act-5 gene expression is limited to microvillus-containing cells
      within the intestine and excretory systems and that ACT-5 is apically localized
      within intestinal cells. Animals heterozygous for a dominant act-5 mutation
      looked clear and thin and grew slowly. Animals homozygous for either the dominant
      act-5 mutation, or a recessive loss of function mutant, exhibited normal
      morphology and intestinal cell polarity, but died during the first larval stage.
      Ultrastructural analysis revealed a complete loss of intestinal microvilli in
      homozygous act-5 mutants. Forced expression of ACT-1 under the control of the act
      5 promoter did not rescue the lethality of the act-5 mutant. Together with immuno
      electron microscopy experiments that indicated ACT-5 is enriched within
      microvilli themselves, these results suggest a microvillus-specific function for
      act-5, and further, they raise the possibility that specific actins may be
      specialized for building microvilli and related structures.

PMID- 15872089
TI  - Dynamin forms a Src kinase-sensitive complex with Cbl and regulates podosomes and
      osteoclast activity.
AB  - Podosomes are highly dynamic actin-containing adhesion structures found in
      osteoclasts, macrophages, and Rous sarcoma virus (RSV)-transformed fibroblasts.
      After integrin engagement, Pyk2 recruits Src and the adaptor protein Cbl, forming
      a molecular signaling complex that is critical for cell migration, and deletion
      of any molecule in this complex disrupts podosome ring formation and/or decreases
      osteoclast migration. Dynamin, a GTPase essential for endocytosis, is also
      involved in actin cytoskeleton remodeling and is localized to podosomes where it
      has a role in actin turnover. We found that dynamin colocalizes with Cbl in the
      actin-rich podosome belt of osteoclasts and that dynamin forms a complex with Cbl
      in osteoclasts and when overexpressed in 293VnR or SYF cells. The association of
      dynamin with Cbl in osteoclasts was decreased by Src tyrosine kinase activity and
      we found that destabilization of the dynamin-Cbl complex involves the recruitment
      of Src through the proline-rich domain of Cbl. Overexpression of dynamin
      increased osteoclast bone resorbing activity and migration, whereas
      overexpression of dynK44A decreased osteoclast resorption and migration. These
      studies suggest that dynamin, Cbl, and Src coordinately participate in signaling
      complexes that are important in the assembly and remodeling of the actin
      cytoskeleton, leading to changes in osteoclast adhesion, migration, and
      resorption.

PMID- 15872091
TI  - Vav1 and Rac control chemokine-promoted T lymphocyte adhesion mediated by the
      integrin alpha4beta1.
AB  - The chemokine CXCL12 promotes T lymphocyte adhesion mediated by the integrin
      alpha4beta1. CXCL12 activates the GTPase Rac, as well as Vav1, a guanine
      nucleotide exchange factor for Rac, concomitant with up-regulation of alpha4beta1
      dependent adhesion. Inhibition of CXCL12-promoted Rac and Vav1 activation by
      transfection of dominant negative Rac or Vav1 forms, or by transfection of their
      siRNA, remarkably impaired the increase in T lymphocyte attachment to alpha4beta1
      ligands in response to this chemokine. Importantly, inhibition of Vav1 expression
      by RNA interference resulted in a blockade of Rac activation in response to
      CXCL12. Adhesions in flow chambers and soluble binding assays using these
      transfectants indicated that initial ligand binding and adhesion strengthening
      mediated by alpha4beta1 were dependent on Vav1 and Rac activation by CXCL12.
      Finally, CXCL12-promoted T-cell transendothelial migration involving alpha4beta1
      mediated adhesion was notably inhibited by expression of dominant negative Vav1
      and Rac. These results indicate that activation of Vav1-Rac signaling pathway by
      CXCL12 represents an important inside-out event controlling efficient up
      regulation of alpha4beta1-dependent T lymphocyte adhesion.

PMID- 15872092
TI  - Maternal deprivation increases vulnerability to morphine dependence and disturbs
      the enkephalinergic system in adulthood.
AB  - Maternal deprivation can trigger long-lasting molecular and cellular
      modifications in brain functions and might facilitate the appearance of
      pathogenic behaviors. This study focuses on the vulnerability to develop morphine
      dependence in adult rats that were separated from their mother and littermates
      for 3 h per day for 14 d after birth and examines the adaptive changes in the
      enkephalinergic pathways. Place-preference conditioning was observed with 2 mg/kg
      morphine in deprived rats, whereas 5 mg/kg morphine was necessary to induce
      conditioning in nondeprived animals. A prolonged morphine conditioning was shown
      in deprived rats. A strong increase in oral morphine self-administration behavior
      and preference was observed in deprived rats. Only a very slight increase in
      preference for sucrose solution, a more ethological reinforcer known to interact
      with the opioid system, was shown in deprived rats. These results indicate that
      this postnatal environment change leads to a hypersensitivity to the reinforcing
      properties of morphine and to the development of morphine dependence. A
      significant decrease in preproenkephalin mRNA expression was observed in the
      nucleus accumbens and the caudate-putamen nucleus of deprived rats. The basal
      extracellular levels of the Met-enkephalin-like immunoreactivity in the nucleus
      accumbens were significantly lower in deprived rats when compared with
      nondeprived animals, whereas no change in mu-opioid receptor binding occurred.
      These results strongly support that maternal deprivation leads to a basal
      hypoactivity of the enkephalinergic system and hypersensitivity to morphine
      effects. Together, our results suggest that maternal deprivation in pups likely
      represents a risk factor for morphine dependence in adult rats.

PMID- 15872093
TI  - Schwann cell-specific ablation of laminin gamma1 causes apoptosis and prevents
      proliferation.
AB  - To investigate the function of laminin in peripheral nerve development, we
      specifically disrupted the laminin gamma1 gene in Schwann cells. Disruption of
      laminin gamma1 gene expression resulted in depletion of all other laminin chains
      known to be expressed in Schwann cells. Schwann cells lacking laminin do not
      extend processes required for initiating axonal sorting and mediating axon
      Schwann cell interaction. They fail to downregulate Oct-6 and arrest at the
      premyelinating stage. The impaired axon-Schwann cell interaction prevents
      phosphorylation of beta-neuregulin-1 receptors and results in decreased cell
      proliferation. Postnatally, laminin-null Schwann cells exhibit reduced
      phosphatidylinositol 3 (PI3)-kinase activity and activation of caspase cascades,
      leading to apoptosis. Injection of a laminin peptide into mutant sciatic nerves
      partially restores PI3-kinase activity and reduces apoptotic signals. These
      results demonstrate the following: (1) that laminin initiates axonal sorting and
      mediates axon-Schwann cell interactions required for Schwann cell proliferation
      and differentiation, and (2) that laminin provides a PI3-kinase/Akt-mediated
      Schwann cell survival signal.

PMID- 15872094
TI  - Endogenous activation of kainate receptors regulates glutamate release and
      network activity in the developing hippocampus.
AB  - Kainate receptors (KARs) are highly expressed throughout the neonatal brain, but
      their function during development is unclear. Here, we show that the maturation
      of the hippocampus is associated with a switch in the functional role of
      presynaptic KARs. In a developmental period restricted to the first postnatal
      week, endogenous L-glutamate tonically activates KARs at CA3 glutamatergic
      synapses to regulate release in an action potential-independent manner. At
      synapses onto pyramidal cells, KARs inhibit glutamate release via a G-protein and
      PKC-dependent mechanism. In contrast, at glutamatergic terminals onto CA3
      interneurons, presynaptic KARs can facilitate release in a G-protein-independent
      mechanism. In both cell types, however, KAR activation strongly upregulates
      inhibitory transmission. We show that, through the interplay of these novel
      diverse mechanisms, KARs strongly regulate the characteristic synchronous network
      activity observed in the neonatal hippocampus. By virtue of this, KARs are likely
      to play a central role in the development of hippocampal synaptic circuits.

PMID- 15872095
TI  - Spontaneous recovery from extinction depends on the reconsolidation of the
      acquisition memory in an appetitive learning paradigm in the honeybee (Apis
      mellifera).
AB  - Memory retrieval initiates two consolidation processes: consolidation of an
      extinction memory and reconsolidation of the acquisition memory. The strength of
      the consolidation processes depends on both the strength of the acquisition
      memory and the strength of retrieval trials and is correlated with its
      sensitivity to inhibition. We demonstrate that in the honeybee (Apis mellifera),
      memory retrieval of a consolidated appetitive olfactory memory leads to both
      consolidation processes, depending on the number of retrieval trials. Spontaneous
      recovery from extinction is induced by many (five), but not by few (one and two),
      retrieval trials. Spontaneous recovery is blocked by emetine, an inhibitor of
      protein synthesis. We conclude that reconsolidation of the acquisition memory
      underlies spontaneous recovery.

PMID- 15872096
TI  - The anti-apoptotic, glucocorticoid receptor cochaperone protein BAG-1 is a long
      term target for the actions of mood stabilizers.
AB  - Increasing data suggest that impairments of cellular plasticity/resilience
      underlie the pathophysiology of bipolar disorder. A series of microarray studies
      with validating criteria have recently revealed a common, novel target for the
      long-term actions of the structurally highly dissimilar mood stabilizers lithium
      and valproate: BAG-1 [BCL-2 (B-cell CLL/lymphoma 2)-associated athanogene].
      Because BAG-1 attenuates glucocorticoid receptor (GR) nuclear translocation,
      activates ERK (extracellular signal-regulated kinase) MAP (mitogen-activated
      protein) kinases, and potentiates anti-apoptotic functions of BCL-2, extensive
      additional studies were undertaken. Chronic administration of both agents at
      therapeutic doses increased the expression of BAG-1 in rat hippocampus.
      Furthermore, these findings were validated at the protein level, and the effects
      were seen in a time frame consistent with therapeutic effects and were specific
      for mood stabilizers. Functional studies showed that either lithium or valproate,
      at therapeutically relevant levels, inhibited dexamethasone-induced GR nuclear
      translocation and inhibited GR transcriptional activity. Furthermore, small
      interfering RNA studies showed that these inhibitory effects on GR activity were
      mediated, at least in part, through BAG-1. The observation that BAG-1 inhibits
      glucocorticoid activation suggests that mood stabilizers may counteract the
      deleterious effects of hypercortisolemia seen in bipolar disorder by upregulating
      BAG-1. Additionally, these studies suggest that regulation of GR-mediated
      plasticity may play a role in the treatment of bipolar disorder and raise the
      possibility that agents affecting BAG-1 more directly may represent novel
      therapies for this devastating illness.

PMID- 15872097
TI  - Locus ceruleus control of slow-wave homeostasis.
AB  - Sleep intensity is regulated by the duration of previous wakefulness, suggesting
      that waking results in the progressive accumulation of sleep need (Borbely and
      Achermann, 2000). In mammals, sleep intensity is reflected by slow-wave activity
      (SWA) in the nonrapid eye movement (NREM) sleep electroencephalogram, which
      increases in proportion to the time spent awake. However, the mechanisms
      responsible for the increase of NREM SWA after wakefulness remain unclear.
      According to a recent hypothesis (Tononi and Cirelli, 2003), the increase in SWA
      occurs because during wakefulness, many cortical circuits undergo synaptic
      potentiation, as evidenced by the widespread induction of long-term potentiation
      (LTP)-related genes in the brain of awake animals. A direct prediction of this
      hypothesis is that manipulations interfering with the induction of LTP-related
      genes should result in a blunted SWA response. Here, we examined SWA response in
      rats in which cortical norepinephrine (NA) was depleted, a manipulation that
      greatly reduces the induction of LTP-related genes during wakefulness (Cirelli
      and Tononi, 2004). We found that the homeostatic response of the lower-range SWA
      was markedly and specifically reduced after NA depletion. These data suggest that
      the wake-dependent accumulation of sleep need is causally related to cellular
      changes dependent on NA release, such as the induction of LTP-related genes, and
      support the hypothesis that sleep SWA homeostasis may be related to synaptic
      potentiation during wakefulness.

PMID- 15872098
TI  - Cocaine-induced reinstatement requires endogenous stimulation of mu-opioid
      receptors in the ventral pallidum.
AB  - The projection from the nucleus accumbens to the ventral pallidum regulates the
      reinstatement of cocaine seeking in rats extinguished from cocaine self
      administration. This projection coexpresses GABA and enkephalin, posing a role
      for mu-opioid receptors in the ventral pallidum in mediating the reinstatement of
      cocaine seeking. Rats were extinguished from cocaine self-administration, and the
      reinstatement of active lever pressing by cocaine was blocked by intra-ventral
      pallidum administration of the mu receptor antagonist Cys-Tyr-D-Trp-Arg-Thr-Pen
      Thr-NH2 (CTAP) (0.03-3.0 microg). Conversely, stimulating mu receptors with
      morphine (1-30 microg) in the ventral pallidum reinstated cocaine seeking. The
      ability of intra-ventral pallidum morphine to reinstate lever pressing was
      blocked by co-microinjection of the mu antagonist CTAP and was augmented by
      systemic cocaine administration. The reinstatement of cocaine seeking was
      associated with reduced extracellular GABA in the ventral pallidum, and the
      reduction in GABA was also prevented by blocking mu receptors with CTAP (10
      microm). Although immunoblotting revealed that neither the total tissue
      concentration nor the membrane insertion of mu receptors in the ventral pallidum
      was altered by withdrawal from cocaine, the capacity of morphine (0.01-10 microm)
      to reduce ventral pallidum levels of extracellular GABA was augmented in rats
      extinguished from cocaine self-administration. These data are consistent with the
      reinstatement of cocaine seeking being modulated in part by coreleased enkephalin
      and GABA from the accumbens-ventral pallidal projection, a modulation that may
      involve the inhibition of GABA release by presynaptic mu receptors.

PMID- 15872099
TI  - Short photoperiods impair spatial learning and alter hippocampal dendritic
      morphology in adult male white-footed mice (Peromyscus leucopus).
AB  - Although seasonal changes in brain morphology and function are well established
      in songbirds, seasonal plasticity of brain structure and function remain less
      well documented in mammals. Nontropical animals display many adaptations to
      reduce energy use to survive winter, including cessation of reproductive
      activities. Because of the high energetic costs of brain tissue, we hypothesized
      that male white-footed mice (Peromyscus leucopus) would reduce brain size in
      response to short days as well as regress their reproductive systems. Because
      short days may decrease hippocampal volume and impair spatial learning and memory
      in rodents and because of the potential for seasonal plasticity in the
      hippocampus, we hypothesized that photoperiod alters hippocampal morphology to
      affect spatial learning and memory. Mice housed in either long or short days for
      10 weeks were examined for performance in a water maze; brains were then removed
      and weighed, and hippocampal volumes were determined. We also measured dendritic
      morphology and spine density in the CA1, CA3, and dentate gyrus. Short days
      decreased brain mass and hippocampal volume compared with long days. Short days
      also impaired long-term spatial learning and memory relative to long days but did
      not affect sensory discrimination or other types of memory. Short days decreased
      apical (stratum lacunosum-moleculare) CA1 spine density, as well as increased
      basilar (stratum oriens) CA3 spine density. Results from this study suggest that
      photoperiod alters brain size and morphology, as well as cognitive function.
      Understanding the mechanisms mediating these photoperiod-induced alterations may
      provide insight for treatment of seasonal cognitive and affective disorders.

PMID- 15872100
TI  - Chromatic organization of ganglion cell receptive fields in the peripheral
      retina.
AB  - This study addresses the chromatic properties of receptive fields in the
      subcortical visual pathway of primates. There is agreement that, in the central
      visual field, many cells belonging to the parvocellular (PC) division of the
      subcortical pathway show red-green opponent responses, that a subgroup of cells
      belonging to the koniocellular (KC) pathway shows blue-yellow opponent responses,
      and that magnocellular (MC) pathway cells show only weak signs of chromatic
      input. However, the chromatic properties of ganglion cells in the peripheral
      retina are poorly understood. Here, we measured the temporal-chromatic properties
      of ganglion cells in extracellular in vivo recordings from peripheral macaque
      retina. We show that the chromatic responsivity of peripheral KC ("blue-on") and
      MC cells is very similar to that of their counterparts in the foveal retina. Cone
      opponent responses are expressed only at low temporal frequencies (<10 Hz) in the
      majority of peripheral PC cells, and some peripheral PC cells show non-opponent
      response properties. With these exceptions, the chromatic properties of ganglion
      cells are essentially preserved throughout the first 50 degrees of visual
      eccentricity. The main change seen in passing from foveal to peripheral retina is
      that all ganglion cell classes become more responsive to high temporal-frequency
      modulation.

PMID- 15872101
TI  - The genomic response to retinal disease and injury: evidence for endothelin
      signaling from photoreceptors to glia.
AB  - Regardless of proximal cause, photoreceptor injury or disease almost invariably
      leads to the activation of Muller cells, the principal glial cells in the retina.
      This observation implies the existence of signaling systems that inform Muller
      cells of the health status of photoreceptors. It further suggests that diverse
      types of photoreceptor damage elicit a limited range of biochemical responses.
      Using the mouse retina, we show by microarray, RNA blot, and in situ
      hybridization that the genomic responses to both light damage and inherited
      photoreceptor degeneration involve a relatively small number of genes and that
      the genes activated by these two insults overlap substantially with one another
      and with the genes activated by retinal detachment. Among the induced
      transcripts, those coding for endothelin2 (Edn2) are unusual in that they are
      localized to photoreceptors and are also highly induced in all of the tested
      models of photoreceptor disease or injury. Acute light damage also leads to a >10
      fold increase in endothelin receptor B (Ednrb) in Muller cells 24 h after injury.
      These observations suggest that photoreceptor-derived EDN2 functions as a general
      stress signal, that EDN2 signals to Muller cells by binding to EDNRB, and that
      Muller cells can increase their sensitivity to EDN2 as part of the injury
      response.

PMID- 15872102
TI  - Respiratory abnormalities resulting from midcervical spinal cord injury and their
      reversal by serotonin 1A agonists in conscious rats.
AB  - Respiratory dysfunction after cervical spinal cord injury (SCI) has not been
      examined experimentally using conscious animals, although clinical SCI most
      frequently occurs in midcervical segments. Here, we report a C5 hemicontusion SCI
      model in rats with abnormalities that emulate human post-SCI pathophysiology,
      including spontaneous recovery processes. Post-C5 SCI rats demonstrated deficits
      in minute ventilation (Ve) responses to a 7% CO2 challenge that correlated
      significantly with lesion severities (no injury or 12.5, 25, or 50 mm x 10 g
      weight drop; New York University impactor; p < 0.001) and ipsilateral motor
      neuron loss (p = 0.016). Importantly, C5 SCI resulted in at least 4 weeks of
      respiratory abnormalities that ultimately recovered afterward. Because serotonin
      is involved in respiration-related neuroplasticity, we investigated the impact of
      activating 5-HT1A receptors on post-C5 SCI respiratory dysfunction. Treatment
      with the 5-HT1A agonist 8-hydroxy-2-(di-n-propylmino)tetralin (8-OH DPAT) (250
      microg/kg, i.p.) restored hypercapnic Ve at 2 and 4 weeks after injury (i.e.,
      approximately 39.2% increase vs post-SCI baseline; p < or = 0.033). Improvements
      in hypercapnic Ve response after single administration of 8-OH DPAT were dose
      dependent and lasted for approximately 4 h(p < or = 0.038 and p < or = 0.024,
      respectively). Treatment with another 5-HT1A receptor agonist, buspirone (1.5
      mg/kg, i.p.), replicated the results, whereas pretreatment with a 5-HT1A-specific
      antagonist, 4-iodo-N-[2-[4(methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl
      benzamide (3 mg/kg, i.p.) given 20 min before 8-OH DPAT negated the effect of 8
      OH DPAT. These results imply a potential clinical use of 5-HT1A agonists for post
      SCI respiratory disorders.

PMID- 15872103
TI  - Common input across motor nuclei mediating precision grip in humans.
AB  - Short-term synchrony was measured for pairs of motor units located within and
      across muscles activated during a task that mimicked precision grip in the
      dominant and nondominant hands of human subjects. Surprisingly, synchrony for
      pairs of motor units residing in separate muscles (flexor pollicis longus, a
      thumb muscle, and flexor digitorum profundus, an index-finger muscle) was just as
      large as that for pairs of units both within the thumb muscle. Furthermore, the
      high level of synchrony seen across muscles in the dominant hand was absent in
      the nondominant hand. These results suggest that descending pathways diverge to
      provide extensive common input across motor nuclei involved in the precision grip
      and that such divergence might contribute to the preferred use of one hand over
      the other.

PMID- 15872104
TI  - Control of cellular pattern formation in the vertebrate inner retina by homotypic
      regulation of cell-fate decisions.
AB  - The vertebrate retina is composed of cellular arrays that are nonrandom across
      two-dimensional space. The determinants of these nonrandom two-dimensional
      cellular patterns in the inner nuclear layer of the retina were investigated
      using empirical and computational modeling techniques. In normal and experimental
      models of goldfish retinal growth, the patterns of tyrosine hydroxylase- and
      serotonin-positive cells indicated that neither cell death nor lateral migration
      of differentiated cells were dominant mechanisms of cellular pattern formation. A
      computational model of cellular pattern formation that used a signaling mechanism
      arising from differentiated cells that inhibited homotypic cell-fate decisions
      generated accurate simulations of the empirically observed patterns in normal
      retina. This model also predicted the principal atypical cellular pattern
      characteristic, a transient cell-type-specific hyperplasia, which was empirically
      observed in the growing retina subsequent to selective ablation of differentiated
      retinal cells, either tyrosine hydroxylase positive or serotonin positive. The
      results support the hypothesis that inhibitory spatiotemporal regulation of
      homotypic cell-fate decisions is a dominant mechanistic determinant of nonrandom
      cellular patterns in the vertebrate retina.

PMID- 15872105
TI  - GABAA-mediated inhibition of basolateral amygdala blocks reward devaluation in
      macaques.
AB  - Amygdala ablation disrupts reinforcer "devaluation" in monkeys (Malkova et al.,
      1997). Here, we tested the hypothesis that transient inactivation of amygdala by
      the GABA(A) agonist muscimol (MUS), specifically during the period of reward
      satiation, would have a similar effect. Six pigtail macaques were trained on a
      visual object discrimination task in which 60 objects were associated with one of
      two specific food rewards. Subsequently, we evaluated the selective satiation
      induced change (devaluation) in object preference in probe sessions. We also
      examined the effect of the amygdala inactivation during the probe sessions to
      determine whether the inactivation limited to the testing period (and not during
      the satiation period) is sufficient to impair the expression of reinforcer
      devaluation. MUS infusions were aimed at basolateral amygdala (BLA) in a
      pseudorandomized design; each monkey received MUS or saline either before or
      after selective satiation with each of the two food rewards (six infusions
      total). Under the control (saline) condition, the monkeys significantly shifted
      their preference from objects representing the sated food rewards to those
      representing the nonsated rewards (30% change). When BLA was inactivated during
      selective satiation (i.e., MUS infused before satiation), this devaluation effect
      was blocked. In contrast, MUS infusion after satiation, so that it was present
      just during the testing period, did not impair the shift in object preference
      (27% change). Thus, BLA is necessary for the appropriate registration of the
      change in the reinforcer value but not for the subsequent expression of the
      devaluation involving its transfer to secondary reinforcers.

PMID- 15872106
TI  - Key role of the postsynaptic density scaffold proteins Shank and Homer in the
      functional architecture of Ca2+ homeostasis at dendritic spines in hippocampal
      neurons.
AB  - A key aspect of postsynaptic function, also important for plasticity, is the
      segregation within dendritic spines of Ca2+ rises attributable to release from
      intracellular stores. Previous studies have shown that overexpression in
      hippocampal neurons of two postsynaptic density (PSD) scaffold proteins, Shank1B
      and Homer1b, induces spine maturation, including translocation of the
      intracellular Ca2+ channel inositol trisphosphate receptor (IP3R). The structural
      and functional significance of these processes remained undefined. Here, we show
      that in its relocation, IP3R is accompanied by other endoplasmic reticulum (ER)
      proteins: the Ca2+ pump sarcoendoplasmic reticulum calcium ATPase, the lumenal
      Ca2+-binding protein calreticulin, the ER lumen-addressed green fluorescent
      protein, and, to a lesser extent, the membrane chaperone calbindin. The
      specificity of these translocations was demonstrated by their inhibition by both
      a Shank1 fragment and the dominant-negative Homer1a. Activation in Shank1B
      transfected neurons of the metabotropic glutamatergic receptors 1/5 (mGluRs1/5),
      which induce IP3 generation with ensuing Ca2+ release from the stores, triggered
      considerable increases in Ca2+-dependent responses: activation of the big K+
      channel, which was revealed by patch clamping, and extracellular signal-regulated
      protein kinase (ERK) phosphorylation. The interaction of Shank1B and Homer1b
      appears as the molecular mechanism linking mGluRs1/5, strategically located in
      the spines, to IP3R with the integration of entire ER cisternas in the PSD and
      with consequences on both local Ca2+ homeostasis and overall neuronal signaling.

PMID- 15872107
TI  - An event-related functional magnetic resonance imaging study of voluntary and
      stimulus-driven orienting of attention.
AB  - Attention can be voluntarily directed to a location or automatically summoned to
      a location by a salient stimulus. We compared the effects of voluntary and
      stimulus-driven shifts of spatial attention on the blood oxygenation level
      dependent signal in humans, using a method that separated preparatory activity
      related to the initial shift of attention from the subsequent activity caused by
      target presentation. Voluntary shifts produced greater preparatory activity than
      stimulus-driven shifts in the frontal eye field (FEF) and intraparietal sulcus,
      core regions of the dorsal frontoparietal attention network, demonstrating their
      special role in the voluntary control of attention. Stimulus-driven attentional
      shifts to salient color singletons recruited occipitotemporal regions, sensitive
      to color information and part of the dorsal network, including the FEF,
      suggesting a partly overlapping circuit for endogenous and exogenous orienting.
      The right temporoparietal junction (TPJ), a core region of the ventral
      frontoparietal attention network, was strongly modulated by stimulus-driven
      attentional shifts to behaviorally relevant stimuli, such as targets at
      unattended locations. However, the TPJ did not respond to salient, task
      irrelevant color singletons, indicating that behavioral relevance is critical for
      TPJ modulation during stimulus-driven orienting. Finally, both ventral and dorsal
      regions were modulated during reorienting but significantly only by reorienting
      after voluntary shifts, suggesting the importance of a mismatch between
      expectation and sensory input.

PMID- 15872108
TI  - Activation of early silent synapses by spontaneous synchronous network activity
      limits the range of neocortical connections.
AB  - During the early development of neocortical networks, many glutamatergic synapses
      lack AMPA receptors and are physiologically silent. We show in neocortical
      cultures that spontaneous synchronous network activity is able to convert silent
      synapses to active synapses by the incorporation of AMPA receptors into synaptic
      complexes throughout the network within a few minutes. To test the effect of
      synaptic activation on the connectivity of neuronal populations, we created
      separated neuronal networks that could innervate each other. We allowed
      outgrowing axons to invade the neighboring network either before or after the
      onset of synchronous network activity. In the first case, both subnetworks
      connected to each other and synchronized their activity, whereas in the second
      case, axonal connections failed to form and network activity did not synchronize
      between compartments. We conclude that early spontaneous synchronous network
      activity triggers a global AMPAfication of immature synapses, which in turn
      prevents later-arriving axons from forming afferent connections. This activity
      dependent process may set the range of corticocortical connections during early
      network development before experience-dependent mechanisms begin elaborating the
      mature layout of the neocortical connections and modules.

PMID- 15872109
TI  - Multisensory space representations in the macaque ventral intraparietal area.
AB  - Animals can use different sensory signals to localize objects in the environment.
      Depending on the situation, the brain either integrates information from multiple
      sensory sources or it chooses the modality conveying the most reliable
      information to direct behavior. This suggests that somehow, the brain has access
      to a modality-invariant representation of external space. Accordingly, neural
      structures encoding signals from more than one sensory modality are best suited
      for spatial information processing. In primates, the posterior parietal cortex
      (PPC) is a key structure for spatial representations. One substructure within
      human and macaque PPC is the ventral intraparietal area (VIP), known to represent
      visual, vestibular, and tactile signals. In the present study, we show for the
      first time that macaque area VIP neurons also respond to auditory stimulation.
      Interestingly, the strength of the responses to the acoustic stimuli greatly
      depended on the spatial location of the stimuli [i.e., most of the auditory
      responsive neurons had surprisingly small spatially restricted auditory receptive
      fields (RFs)]. Given this finding, we compared the auditory RF locations with the
      respective visual RF locations of individual area VIP neurons. In the vast
      majority of neurons, the auditory and visual RFs largely overlapped.
      Additionally, neurons with well aligned visual and auditory receptive fields
      tended to encode multisensory space in a common reference frame. This suggests
      that area VIP constitutes a part of a neuronal circuit involved in the
      computation of a modality-invariant representation of external space.

PMID- 15872110
TI  - Lesions of orbitofrontal cortex impair rats' differential outcome expectancy
      learning but not conditioned stimulus-potentiated feeding.
AB  - Patients with damage to the orbitofrontal cortex (OFC) display various
      impairments in cognitive and affective function, including a reduced ability to
      use information about the consequences of their actions to guide their behavior.
      In this study, rats with neurotoxic lesions of the OFC failed to use specific
      expectancies about outcomes to guide their learning of an instrumental
      discrimination task. In contrast, lesioned rats were unimpaired in a measure of
      learned motivational function, the potentiation of feeding under conditions of
      food satiation, by a conditioned stimulus that had been paired with food while
      the rats were food deprived. Notably, performance of both of these tasks has been
      shown to depend on the function of the basolateral amygdala (BLA), a region that
      is richly interconnected with the OFC. Thus, the present results are consistent
      with the view that the acquisition and use of specific outcome expectancies to
      guide behavior critically involve a neural system that includes the BLA and the
      OFC, but they indicate that certain motivational properties acquired by cues on
      the basis of appetitive learning involve BLA circuitry apart from the OFC.

PMID- 15872111
TI  - Kinetics of exocytosis is faster in cones than in rods.
AB  - Cone-driven responses of second-order retinal neurons are considerably faster
      than rod-driven responses. We examined whether differences in the kinetics of
      synaptic transmitter release from rods and cones may contribute to differences in
      postsynaptic response kinetics. Exocytosis from rods and cones was triggered by
      membrane depolarization and monitored in two ways: (1) by measuring EPSCs evoked
      in second-order neurons by depolarizing steps applied to presynaptic rods or
      cones during simultaneous paired whole-cell recordings or (2) by direct
      measurements of exocytotic increases in membrane capacitance. The kinetics of
      release was assessed by varying the length of the depolarizing test step. Both
      measures of release revealed two kinetic components to the increase in exocytosis
      as a function of the duration of a step depolarization. In addition to slow
      sustained components in both cell types, the initial fast component of exocytosis
      had a time constant of <5 ms in cones, >10-fold faster than that of rods.
      Rod/cone differences in the kinetics of release were substantiated by a linear
      correlation between depolarization-evoked capacitance increases and EPSC charge
      transfer. Experiments on isolated rods indicate that the slower kinetics of
      exocytosis from rods was not a result of rod-rod coupling. The initial rapid
      release of vesicles from cones can shape the postsynaptic response and may
      contribute to the faster responses of cone-driven cells observed at light offset.

PMID- 15872112
TI  - Double dissociation of exteroceptive and interoceptive feedback systems in the
      orbital and ventromedial prefrontal cortex of humans.
AB  - The primate ventral prefrontal cortex contains two densely interconnected
      subregions: a lateral/orbital cortex processing primarily sensory/exteroceptive
      information, and a ventromedial cortex processing primarily
      visceroappetitive/interoceptive information. These regions have major afferents
      from and efferents to other associative cortices. The organization of these
      structures leads to an hypothesized role in feedback processing. We use
      neuroimaging to test this model, defined so far mostly through anatomical
      studies. Healthy volunteers were trained operantly on a transitive inference task
      (A>B, B>C ==> A>C) requiring flexible manipulation of feedback to solve. Two
      groups of subjects learned an arbitrary face hierarchy, one adjacent face pair at
      a time; each group received either visual/exteroceptive ("XXXX") or
      visceroappetitive/interoceptive (fruit juice) feedback for correct responses to
      adjacent face pairs. After task acquisition, the subjects were tested on novel
      stimulus pairs (i.e., nonadjacent, TEST) derived from the acquired hierarchy. The
      TEST condition required transitive inference. No feedback was provided during
      TEST. Brain activity during TEST in the group trained with visual/exteroceptive
      feedback increased in the orbital prefrontal cortex and decreased in the
      ventromedial prefrontal cortex. In contrast, brain activity during TEST in the
      group trained with visceroappetitive/interoceptive feedback decreased in the
      orbital prefrontal cortex and increased in the ventromedial prefrontal cortex.
      These results provide functional evidence, consistent with previous anatomical
      studies, for two major feedback systems in human ventral prefrontal cortex: a
      lateral system specialized for exteroceptive information and a medial system
      specialized for interoceptive information. Although highly interconnected, there
      is a double dissociation of function between these networks in healthy humans.

PMID- 15872113
TI  - Calcineurin triggers reactive/inflammatory processes in astrocytes and is
      upregulated in aging and Alzheimer's models.
AB  - Astrocyte reactivity (i.e., activation) and associated neuroinflammation are
      increasingly thought to contribute to neurodegenerative disease. However, the
      mechanisms that trigger astrocyte activation are poorly understood. Here, we
      studied the Ca2+-dependent phosphatase calcineurin, which regulates inflammatory
      signaling pathways in immune cells, for a role in astrogliosis and brain
      neuroinflammation. Adenoviral transfer of activated calcineurin to primary rat
      hippocampal cultures resulted in pronounced thickening of astrocyte somata and
      processes compared with uninfected or virus control cultures, closely mimicking
      the activated hypertrophic phenotype. This effect was blocked by the calcineurin
      inhibitor cyclosporin A. Parallel microarray studies, validated by extensive
      statistical analyses, showed that calcineurin overexpression also induced genes
      and cellular pathways representing most major markers associated with astrocyte
      activation and recapitulated numerous changes in gene expression found previously
      in the hippocampus of normally aging rats or in Alzheimer's disease (AD). No
      genomic or morphologic evidence of apoptosis or damage to neurons was seen,
      indicating that the calcineurin effect was mediated by direct actions on
      astrocytes. Moreover, immunocytochemical studies of the hippocampus/neocortex in
      normal aging and AD model mice revealed intense calcineurin immunostaining that
      was highly selective for activated astrocytes. Together, these studies show that
      calcineurin overexpression is sufficient to trigger essentially the full genomic
      and phenotypic profiles associated with astrocyte activation and that
      hypertrophic astrocytes in aging and AD models exhibit dramatic upregulation of
      calcineurin. Thus, the data identify calcineurin upregulation in astrocytes as a
      novel candidate for an intracellular trigger of astrogliosis, particularly in
      aging and AD brain.

PMID- 15872114
TI  - Neural cell adhesion molecule-secreting transgenic mice display abnormalities in
      GABAergic interneurons and alterations in behavior.
AB  - The extracellular region of the transmembrane neural cell adhesion molecule (NCAM
      EC) is shed as a soluble fragment at elevated levels in the schizophrenic brain.
      A novel transgenic mouse line was generated to identify consequences on cortical
      development and function of expressing soluble NCAM-EC from the neuron-specific
      enolase promoter in the developing and mature neocortex and hippocampus. NCAM-EC
      transgenic mice exhibited a striking reduction in synaptic puncta of GABAergic
      interneurons in the cingulate, frontal association cortex, and amygdala but not
      hippocampus, as shown by decreased immunolabeling of glutamic acid decarboxylase
      65 (GAD65), GAD67, and GABA transporter 1. Interneuron cell density was unaltered
      in the transgenic mice. Affected subpopulations of interneurons included basket
      interneurons evident in NCAM-EC transgenic mice intercrossed with a reporter line
      expressing green fluorescent protein and by parvalbumin staining. In addition,
      there appeared to be a reduction in excitatory synapses, as revealed by
      synaptophysin staining and apical dendritic spine density of cortical pyramidal
      cells. Behavioral analyses demonstrated higher basal locomotor activity of NCAM
      EC mice and enhanced responses to amphetamine and (+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5,10-imine maleate compared with wild-type controls.
      Transgenic mice were deficient in prepulse inhibition, which was restored by
      clozapine but not by haloperidol. Additionally, NCAM-EC mice were impaired in
      contextual and cued fear conditioning. These results suggested that elevated
      shedding of NCAM perturbs synaptic connectivity of GABAergic interneurons and
      produces abnormal behaviors that may be relevant to schizophrenia and other
      neuropsychiatric disorders.

PMID- 15872115
TI  - Galphao2 regulates vesicular glutamate transporter activity by changing its
      chloride dependence.
AB  - Classical neurotransmitters, including monoamines, acetylcholine, glutamate,
      GABA, and glycine, are loaded into synaptic vesicles by means of specific
      transporters. Vesicular monoamine transporters are under negative regulation by
      alpha subunits of trimeric G-proteins, including Galpha(o2) and Galpha(q).
      Furthermore, glutamate uptake, mediated by vesicular glutamate transporters
      (VGLUTs), is decreased by the nonhydrolysable GTP-analog
      guanylylimidodiphosphate. Using mutant mice lacking various Galpha subunits,
      including Galpha(o1), Galpha(o2), Galpha(q), and Galpha11, and a Galpha(o2)
      specific monoclonal antibody, we now show that VGLUTs are exclusively regulated
      by Galpha(o2). G-protein activation does not affect the electrochemical proton
      gradient serving as driving force for neurotransmitter uptake; rather, Galpha(o2)
      exerts its action by specifically affecting the chloride dependence of VGLUTs.
      All VGLUTs show maximal activity at approximately 5 mm chloride. Activated
      Galpha(o2) shifts this maximum to lower chloride concentrations. In contrast,
      glutamate uptake by vesicles isolated from Galpha(o2-/-) mice have completely
      lost chloride activation. Thus, Galpha(o2) acts on a putative regulatory chloride
      binding domain that appears to modulate transport activity of vesicular glutamate
      transporters.

PMID- 15872116
TI  - A pregnane X receptor agonist with unique species-dependent stereoselectivity and
      its implications in drug development.
AB  - Pregnane X receptor (PXR) is an orphan nuclear receptor that regulates the
      expression of genes encoding drug-metabolizing enzymes and transporters. In
      addition to affecting drug metabolism, potent and selective PXR agonists may also
      have therapeutic potential by removing endogenous and exogenous toxins. In this
      article, we report the synthesis and identification of novel PXR agonists from a
      library of peptide isosteres. Compound S20, a C-cyclopropylalkylamide, was found
      to be a PXR agonist with both enantiomer- and species-specific selectivity. S20
      has three chiral carbons and was resolved into its two enantiomers. The
      individual S20 enantiomers exhibited striking mouse/human-specific PXR
      activation, whereby enantiomer (+)-S20 preferentially activated hPXR, and
      enantiomer (-)-S20 was a better activator for mPXR. As a human PXR (hPXR)
      agonist, (+)-S20 was more potent and efficacious than rifampicin. Mutagenesis
      studies revealed that the ligand binding domain residue Phe305 is critical for
      the preference for the (-)-S20 enantiomer by the rodent PXR. Treatment of S20
      induced the expression of drug-metabolizing enzymes and transporters in reporter
      gene assays, in primary human hepatocytes, and in "humanized" hPXR transgenic
      mice. To our knowledge, S20 represents the first compound whose enantiomers have
      opposite species preference in activating a xenobiotic receptor. The
      stereoselectivity may be used to guide the development of safer drugs to avoid
      drug-drug interactions or to achieve human-specific therapeutic effects when a
      xenobiotic receptor is being used as a drug target.

PMID- 15872117
TI  - Novel mechanism of inhibition of nuclear factor-kappa B DNA-binding activity by
      diterpenoids isolated from Isodon rubescens.
AB  - The development of specific inhibitors that can block nuclear factor-kappaB (NF
      kappaB) activation is an approach for the treatment of cancer, autoimmune, and
      inflammatory diseases. Several diterpenoids, oridonin, ponicidin, xindongnin A,
      and xindongnin B were isolated from the herb Isodon rubescens. These compounds
      were found to be potent inhibitors of NF-kappaB transcription activity and the
      expression of its downstream targets, cyclooxygenase-2 and inducible nitric-oxide
      synthase. The mechanisms of action of the diterpenoids against NF-kappaB are
      similar, but significant differences were also identified. All of the
      diterpenoids directly interfere with the DNA-binding activity of NF-kappaB to its
      response DNA sequence. Oridonin and ponicidin have an additional impact on the
      translocation of NF-kappaB from the cytoplasm to nuclei without affecting IkappaB
      alpha phosphorylation and degradation. The effect of these compounds on the
      interaction of NF-kappaB with consensus DNA sequences is unique. Different
      inhibitory effects were observed when NF-kappaB bound to various DNA sequences.
      Both p65/p65 and p50/p50 homodimers, as well as p65/p50 heterodimer association
      with their responsive DNA, were inhibited. Kinetic studies on NF-kappaB-DNA
      interaction indicate that the diterpenoids decrease the B(max app) but have no
      effect on K(d app). This suggests that this class of compounds interacts with
      both p65 and p50 subunits at a site other than the DNA binding site and
      subsequently modulates the binding affinity of the transcription factor toward
      DNA with different NF-kappaB binding sequences. The diterpenoid structure could
      therefore serve as a scaffold for the development of more potent and selective NF
      kappaB inhibitors that target regulated gene transcription.

PMID- 15872118
TI  - Molecular basis of inward rectification: structural features of the blocker
      defined by extended polyamine analogs.
AB  - Polyamines cause inward rectification of Kir K(+) channels by blocking deep
      within the channel pore. We investigated structural constraints of polyamine
      block of strongly rectifying mutant K(ATP) channels (Kir6.2[L164C,N160D,C166S] +
      SUR1). We studied three groups of polyamine analogs: 1) conformationally
      restricted linear tetra-amines with a cycloalkyl or alkene group between the
      second and third amines (CGC-11047, CGC-11093, CGC-11099, and CGC-11098), 2)
      conformationally restricted linear deca-amines with a cycloalkyl or alkene group
      between the fifth and sixth amines (CGC-11150, CGC-11179, and CGC-11241), and 3)
      cyclic tetra-amines (CGC-11174, CGC-11197, CGC-11199, and CGC-11254). All linear
      analogs cause a voltage-dependent block similar to that of spermine, but slightly
      weaker (at 1 microM, V(1/2) for spermine block = -10 +/- 1 mV, Z = 2.9 +/- 0.1, n
      = 19; V(1/2) for analogs varies from polyamine -7 to +10 mV, Z = 2.6-3.9). These
      data indicate tolerance for conformational restriction and an upper limit to the
      voltage dependence of the blocking process. There was no voltage-dependent block
      by the cyclic compounds; instead, they induce irreversible rundown of the
      current. Structural models of Kir channels suggest that a narrow entry at the top
      of the cytoplasmic pore may exclude cyclic analogs from the inner cavity, thereby
      explaining the structure-activity relationship that we observe.

PMID- 15872119
TI  - Ropivacaine cardiac toxicity--not as troublesome as bupivacaine.

PMID- 15872120
TI  - Neuraxial anesthesia and multiple sclerosis.

PMID- 15872121
TI  - Improving patient safety in critical care: big challenge, exciting opportunity.

PMID- 15872122
TI  - A dopamine infusion decreases propofol concentration during epidural blockade
      under general anesthesia.
AB  - PURPOSE: It is common clinical practice to use dopamine to manage the reduction
      in blood pressure accompanying epidural blockade. As propofol is a high-clearance
      drug, propofol concentrations can be influenced by cardiac output (CO). The
      purpose of the present study was to investigate the effects of dopamine infusions
      on propofol concentrations administered by a target-controlled infusion system
      during epidural block under general anesthesia. METHODS: 12 patients undergoing
      abdominal surgery were enrolled in this study. Anesthesia was induced with
      propofol and vecuronium 0.1 mg.kg(-1), and maintained using 67% nitrous oxide,
      sevoflurane in oxygen and constant infusion of propofol. Propofol was
      administered to all subjects via target-controlled infusion to achieve a propofol
      concentration at 6.0 microg.mL(-1) at intubation and 2.0 microg.mL(-1) after
      intubation. Before and after the administration of 10 mL of 1.5% mepivacaine from
      the epidural catheter and dopamine infusion at 5 microg.kg(-1).min(-1), CO and
      effective liver blood flow (LBF) were measured using indocyanine green. Blood
      propofol concentration was also determined using high-performance liquid
      chromatography. RESULTS: At one hour after epidural block and dopamine infusion,
      CO was significantly increased from 4.30 +/- 1.07 L.min(-1) to 5.82 +/- 0.98
      L.min(-1) (P < 0.0001), and effective LBF was increased 0.75 +/- 0.17 L.min(-1)
      to 0.96 +/- 0.18 L.min(-1) (P < 0.0001). Propofol concentration was significantly
      decreased from 2.13 +/- 0.24 microg.mL(-1) to 1.59 +/- 0.29 microg.mL(-1) (P <
      0.0001). CONCLUSIONS: Propofol concentrations decrease with an increase in CO,
      suggesting the possibility of inadequate anesthetic depth following catecholamine
      infusion during propofol anesthesia.

PMID- 15872123
TI  - Delayed recovery of vecuronium neuromuscular block in diabetic patients during
      sevoflurane anesthesia.
AB  - PURPOSE: To study recovery from vecuronium-induced neuromuscular block in
      diabetic patients during total iv or sevoflurane anesthesia. METHODS: 30 diabetic
      patients were assigned to diabetes mellitus (DM)-total iv anesthesia (TIVA); (n =
      15) or DM-sevoflurane (S) groups (n = 15). Thirty healthy patients were divided
      into control-TIVA (n = 15) or control-S groups (n = 15). In the DM-TIVA or
      control-TIVA groups and DM-S or control-S groups, anesthesia was maintained with
      propofol and fentanyl, and nitrous oxide-oxygen-sevoflurane 1.7%, respectively.
      After receiving vecuronium 0.1 mg.kg(-1)iv, recovery of the train-of-four (TOF)
      was compared among the four groups. RESULTS: Times to the return of T2, T3, or T4
      in the DM-TIVA and DM-S groups were longer than in the control-TIVA and control-S
      groups (46.9 +/- 13.8 vs 32.2 +/- 10.7 and 32.6 +/- 8.7 min for T2, P < 0.05).
      T1/control in the DM-S group was less than in the control-TIVA and DM-TIVA groups
      50 to 120 and 70 to 120 min after receiving vecuronium, respectively (P < 0.05).
      T1/control in the control-S group was less than in the control-TIVA group 80 to
      120 min after receiving vecuronium (P < 0.05). TOF ratio in the DM-S group was
      less than in the control-TIVA, DM-TIVA, and control-S groups, 60 to 120, 80 to
      120, and 80 to 120 min after receiving vecuronium, respectively (P < 0.05).
      CONCLUSION: In diabetic patients receiving vecuronium, recovery of T1/control and
      TOF ratio are delayed during sevoflurane anesthesia, but not in association with
      total iv anesthesia.

PMID- 15872124
TI  - A lidocaine/metoclopramide combination decreases pain on injection of propofol.
AB  - PURPOSE: Injection pain is a well-known adverse effect of propofol which
      distresses patients. Lidocaine pretreatment is the most popular method for
      reducing this pain but this drug cannot entirely eliminate the problem. The
      purpose of this study was to examine the analgesic effect of
      lidocaine/metoclopramide combination, compared with lidocaine alone, during
      propofol injection. METHODS: In a randomized, double-blind, placebo-controlled
      trial, 90 patients, 40 males and 50 females, scheduled for elective plastic
      surgery received either lidocaine 20 mg plus metoclopramide 10 mg iv, lidocaine
      20 mg iv, or placebo (saline); (n = 30 in each), with venous occlusion for one
      minute, followed by administration of propofol 0.5 mg.kg(-1) into a dorsal hand
      vein. Pain was assessed on a four-point scale (0 = none, 1 = mild, 2 = moderate,
      3 = severe) during propofol injection. RESULTS: 25 patients (83%) complained of
      pain in the placebo group, compared with 12 (40%) in the lidocaine group (P <
      0.05) and three (10%) in the combination group (P < 0.05). Pain score (median)
      was less in the lidocaine (0) and combination (0) groups than in the placebo
      group (2); (P < 0.05). The difference in the incidence of pain between the
      combination and lidocaine groups was significant (P < 0.05). CONCLUSION: A
      lidocaine/metoclopramide combination is more effective than lidocaine alone for
      reducing pain on injection of propofol in a peripheral vein.

PMID- 15872125
TI  - Prospective application of a simplified risk score to prevent postoperative
      nausea and vomiting.
AB  - PURPOSE: To compare the risk-adapted approach with ondansetron against
      ondansetron plus dexamethasone to prevent postoperative nausea and vomiting
      (PONV) in a randomized clinical trial. METHODS: 460 patients scheduled for
      elective surgery were enrolled in this prospective study and stratified according
      to a simplified risk score for PONV. Patients having no or one risk factor were
      considered at low risk (group L) and did not receive study medication. Those with
      two to four risk factors were considered high risk and were randomized to receive
      4 mg ondansetron plus placebo (group H-O) or 4 mg ondansetron plus 8 mg
      dexamethasone (group H-OD). Incidence and intensity of PONV were observed for 24
      hr after surgery. Data were analyzed with Fisher's exact or Student's t tests; P
      < 0.05 was considered statistically significant. RESULTS: The incidence of PONV
      was 9% in group L (n = 87), 31% in those receiving ondansetron (group H-O, n =
      185), and 22% in those receiving both drugs (group H-OD, n = 181). The incidence
      of PONV was significantly smaller in both high-risk groups than predicted without
      treatment (P < 0.001). While the incidence of PONV failed statistical
      significance between the two intervention groups (P = 0.08), the mean number of
      episodes of PONV and the mean maximal intensity of each episode of PONV were
      lower in group H-OD (P = 0.03 and P = 0.01, respectively). Patients of group H-OD
      required less antiemetic rescue therapy (P = 0.004). CONCLUSIONS: Ondansetron
      plus dexamethasone prevents PONV more effectively than ondansetron alone in
      patients at high risk for PONV.

PMID- 15872126
TI  - Prevention of PONV by acustimulation with capsicum plaster is comparable to
      ondansetron after middle ear surgery.
AB  - PURPOSE: To compare the efficacy of stimulation of P6 acupoint with capsicum
      plaster in comparison with iv ondansetron for the prevention of postoperative
      nausea and vomiting (PONV). METHODS: 120 patients of either sex, ASA I-II,
      undergoing elective middle ear surgeries under general anesthesia were included
      in this randomized, prospective, double-blinded and placebo-controlled study. The
      anesthetic technique was standardized. Patients were divided into three groups.
      Group I was the control group. Capsicum plaster (1 x 1 cm) was affixed at the P6
      acupoint on both forearms 30 min before induction of anesthesia in patients of
      Group II. Patients of Groups I and III received an inactive adhesive plaster at
      the same site. Ondansetron 4 mg iv was given to patients of Group III at the end
      of surgery and the rest of the patients received a placebo. The plasters were
      removed six hours after transferring the patients to the postoperative unit.
      Criteria were fixed for the administration of rescue antiemetics (ondansetron 4
      mg iv). PONV and the requirement for rescue antiemetics were recorded by a
      blinded observer. RESULTS: The incidence of PONV and the requirement for rescue
      antiemetics were significantly lower in both the acustimulation and ondansetron
      groups at six hours. At 24 hr there was a reduction in the requirement for rescue
      medication in the ondansetron group. CONCLUSION: Stimulation of the P6 acupoint
      with capsicum plaster is an effective method for prevention of PONV after middle
      ear surgery and its efficacy is comparable to ondansetron for the first six hours
      after surgery.

PMID- 15872127
TI  - Successful defibrillation immediately after the intravascular injection of
      ropivacaine.
AB  - PURPOSE: To report successful resuscitation of ventricular fibrillation induced
      by accidental intravascular injection of ropivacaine. CLINICAL FEATURES: A 15-yr
      old healthy girl weighing 59 kg was scheduled for transposition of the tibial
      tuberosity under combined sciatic/three-in-one block. No premedication was given.
      In the induction room, an iv infusion was started, along with electrocardiogram
      monitoring, non-invasive blood-pressure measurement and pulse-oximetry. The
      sciatic nerve was found with the use of a nerve stimulator at the first attempt
      by the classical approach of Labat. Aspiration for blood was negative and the
      injection of ropivacaine 0.75% without epinephrine started. Convulsions, followed
      within seconds by ventricular fibrillation occurred at the end of the injection
      of 18 mL ropivacaine 0.75%. Oxygen was administered by face mask ventilation and
      immediate defibrillation was successful on the second attempt (2 x 200 joules).
      Within two minutes convulsions stopped and normal cardiac rhythm returned.
      Propofol and sufentanil were injected and a laryngeal mask inserted to start
      general anesthesia for surgery. Postoperatively no evidence of sciatic block
      could be demonstrated. The patient did not remember the event and was discharged
      the following day with no residual effects. CONCLUSION: This case report shows
      that ventricular fibrillation after unintentional intravascular injection of
      ropivacaine can be treated successfully when one is prepared and cardiac life
      support measures are taken immediately.

PMID- 15872128
TI  - Prolonged duration of anesthesia in a patient with multiple sclerosis following
      paravertebral block.
AB  - PURPOSE: To explore the possibility that the prolonged duration of anesthesia
      following paravertebral block was related to the presence of multiple sclerosis
      in a patient undergoing elective inguinal hernia repair. CLINICAL FEATURES: A
      healthy 33-yr-old female presented for elective inguinal hernia repair. The
      procedure was performed under general anesthesia and a paravertebral block was
      performed at the end of the procedure for postoperative pain relief, whilst the
      patient was still anesthetized. Upon recovering from general anesthesia it was
      noted that the patient had a flaccid paralysis of both lower extremities. She was
      also very nauseated and required antiemetics and vasopressors for hypotension. A
      differential diagnosis of subarachnoid, subdural or epidural spread was
      considered. The presence of an epidural hematoma was also considered. The block
      regressed very slowly with full return of function in 12.5 hr. The duration of
      action of the block was far longer than one would expect following spinal,
      epidural or subdural spread of a local anesthetic. Urinary catheterization was
      performed electively to prevent urinary retention. The patient was discharged
      home late that evening. Prior to discharge she volunteered that she was being
      investigated for multiple sclerosis. One month later the diagnosis of multiple
      sclerosis was confirmed. CONCLUSION: In conclusion the extended duration of
      central neural blockade following paravertebral block, may have been related to
      an abnormal uptake of local anesthetics into the spinal cord in the presence of
      demyelination.

PMID- 15872129
TI  - Systemic ketamine inhibits hypersensitivity after surgery via descending
      inhibitory pathways in rats.
AB  - PURPOSE: Systemic ketamine suppresses several types of chronic pain. Although
      ketamine is used as a general anesthetic agent, the analgesic effect of systemic
      ketamine for early-stage postoperative pain is not clear. We investigated the
      efficacy and mechanism of systemic ketamine in a rat model of postoperative pain.
      METHODS: An incision was made in the plantar aspect of the left hind paw in male
      Wistar rats. Mechanical hypersensitivity was measured using calibrated von Frey
      filaments. The anti-hypersensitivity effect of systemic or intrathecal
      administration of ketamine was determined every hour after making the incision.
      We examined the effects of intrathecal pretreatment with yohimbine, an alpha2
      adrenoceptor antagonist, and methysergide, a serotonergic receptor antagonist, on
      the anti-hypersensitivity effect of ketamine. We also examined the effect of
      systemic ketamine on the c-fos immunoreactivity in the spinal cord. RESULTS:
      Systemic administration of ketamine at doses from 3 to 30 mg.kg(-1) produced anti
      hypersensitivity effects in a dose-dependent manner. Intrathecal administration
      of ketamine had no effect. There was no significant difference between effects of
      pre- and post-incisional administration. Intrathecal pretreatment with yohimbine
      (10 microg) or methysergide (15 microg) completely reversed the anti
      hypersensitivity effects of systemic ketamine. Systemic ketamine reduced fos
      expression in laminae I-II in the dorsal horn of the lumbar spinal cord
      ipsilateral to the paw incision. CONCLUSIONS: The results suggest that systemic
      administration of ketamine perioperatively suppresses early-stage postoperative
      pain via monoaminergic descending inhibitory pathways.

PMID- 15872130
TI  - High dose nonsteroidal anti-inflammatory drugs compromise spinal fusion.
AB  - PURPOSE: Although nonsteroidal anti-inflammatory drugs (NSAIDs) provide benefit
      to patients following spinal fusion surgery, their routine administration has
      remained controversial due to concerns about possible deleterious effects on bone
      healing. The goal of this retrospective study was to assess the incidence of non
      union following the perioperative administration of ketorolac, celecoxib, or
      rofecoxib. METHODS: We retrospectively analyzed the data of 434 patients
      receiving perioperative ketorolac (20-240 mg.day(-1)), celecoxib (200-600 mg.day(
      1)), rofecoxib (50 mg.day(-1)), or no NSAIDs in the five days following spinal
      fusion surgery. RESULTS: There were no significant differences in the incidence
      of non-union among the groups that received no NSAIDs (11/130; 8.5%), celecoxib
      5/60; 8.3%), or rofecoxib (9/124; 7.3%). In contrast, 23/120 of patients (19.2%)
      that received ketorolac had a higher incidence (P < 0.001) of non-union compared
      to non-NSAID users. However, only 3/50 patients (6%) receiving low-dose ketorolac
      (< or = 110 mg.day(-1)) resulted in non-union which was not significantly
      different from non-NSAID users. Patients administered higher doses of ketorolac
      (120-240 mg.day(-1)) resulted in a higher incidence (P < 0.0001) of non-union
      (20/70; 29%) compared to non-NSAID users. For those patients developing non
      union, there was a higher incidence comparing smokers vs non-smokers (P < 0.0001)
      and one level fusion vs two level fusions (P < 0.001). CONCLUSIONS: This study
      revealed that the short-term perioperative administration of celecoxib,
      rofecoxib, or low-dose ketorolac (< or = 110 mg.day(-1)) had no significant
      deleterious effect on non-union. In contrast, higher doses of ketorolac (120-240
      mg.day(-1)), history of smoking, and two level vertebral fusions resulted in a
      significant increase in the incidence of non-union following spinal fusion
      surgery.

PMID- 15872131
TI  - Review article: perioperative pain management of patients on methadone therapy.
AB  - PURPOSE: Methadone, an opioid traditionally associated with the management of
      opioid addictive disorders, has been prescribed increasingly as an analgesic for
      the management of various chronic pain conditions. Despite the increasing
      popularity of methadone, most anesthesiologists are not familiar with its complex
      pharmacology. The purpose of this article is to review the pharmacology of
      methadone and to suggest a management algorithm for the perioperative care of
      methadone patients. SOURCE: A Medline search was performed to obtain the
      published literature on the pharmacology of methadone and its use
      perioperatively. PRINCIPAL FINDINGS: The complexity of methadone's pharmacology
      is characterized by a high inter-individual variability, a potential for
      interaction with other medications, and a long elimination half-life. The
      postoperative management of methadone patients may be difficult as they are often
      'opioid-tolerant' but may be 'pain-intolerant'. For those patients who are taking
      part in methadone-maintenance programs, there is a potential for the problematic
      use of opioids or other substances. The management plan for patients taking
      methadone may differ depending on the type of surgery and the associated
      perioperative differences in fasting status and gastrointestinal function. In
      consideration of all the factors listed above, a management algorithm is outlined
      for the perioperative care of methadone patients. CONCLUSION: Methadone is an
      opioid with complex properties, and a patient that is taking methadone can
      represent a unique challenge to the anesthesiologist. A good understanding of the
      pharmacology of methadone and of the type of patients on this medication will
      help to improve their perioperative care.

PMID- 15872132
TI  - The ankle clonus test is not a clinically useful measure of spinal cord integrity
      in children.
AB  - PURPOSE: Bilateral flexion-induced ankle clonus has been proposed as a test of
      spinal cord integrity during anesthesia for scoliosis surgery. The purpose of
      this study was to establish the reliability of this test in normal children
      emerging from volatile anesthesia. A secondary objective was to determine if
      there was a difference in the validity of this test with either sevoflurane or
      isoflurane anesthesia. METHODS: In a randomized, prospective blinded clinical
      trial, 32 healthy children aged three to 13 yr, were randomized to receive either
      isoflurane (Group I, n = 15) or sevoflurane (Group S, n = 17) for maintenance of
      anesthesia during dental restorative surgery. During emergence, an observer,
      blinded to group allocation, recorded ankle clonus scores (number of beats to a
      maximum of 5 on each side) at 60-sec intervals until tracheal extubation. End
      tidal anesthetic concentration was measured contemporaneously. RESULTS: Non
      sustained ankle clonus was elicited in a majority of children during emergence:
      13 (87%) patients in Group I and 15 (88%) in Group S demonstrated at least non
      sustained or unilateral clonus. However, bilateral sustained (> 5 beats.min(-1))
      ankle clonus occurred in only four (27%) patients in Group I and four (24%)
      patients in Group S (P = 0.83). CONCLUSION: We conclude that the specificity of
      the ankle clonus test is too low to be clinically useful as a measure of spinal
      cord integrity in children, both when isoflurane and sevoflurane are used as the
      primary anesthetic agent.

PMID- 15872133
TI  - Cardiac output by PulseCO is not interchangeable with thermodilution in patients
      undergoing OPCAB.
AB  - PURPOSE: To investigate the reliability of cardiac output assessed by arterial
      pressure waveform (PulseCO) in comparison with bolus thermodilution measurements
      in patients undergoing off-pump coronary artery bypass grafting (OPCAB). METHODS:
      23 patients who underwent OPCAB were enrolled in this study. After premedication
      with oral diazepam 10 mg, anesthesia was induced with midazolam, fentanyl and
      vecuronium. After induction, radial artery and pulmonary artery catheters were
      inserted. Cardiac output was measured simultaneously by the PulseCO and the bolus
      thermodilution method using the Vigilance monitor: 1) after sternotomy, 2) after
      opening the mediastinum, and 3) at the end of surgery. The PulseCO was calibrated
      initially with cardiac output determined by the thermodilution method after
      induction of anesthesia. RESULTS: The correlation coefficients between the two
      techniques at the three measurement periods were: 1) R2 = 0.49, 2) R2 = 0.52, 3)
      R2 = 0.55. The limits of agreement (bias +/- 2 SD of bias) were: 1) 0.71 +/-
      2.66, 2) 0.30 +/- 1.97, 3) 0.76 +/- 3.85 L.min(-1). CONCLUSIONS: Cardiac output
      by PulseCO is not interchangeable with cardiac output measured by thermodilution
      in patients undergoing OPCAB.

PMID- 15872134
TI  - Adherence to simple and effective measures reduces the incidence of ventilator
      associated pneumonia.
AB  - PURPOSE: Several modalities have been shown to be individually effective in
      reducing the incidence (and hence associated morbidity, mortality, and costs) of
      ventilator-associated pneumonia, but their implementation into clinical practice
      is inconsistent. We introduced an intensive care unit protocol and measured its
      effect on ventilator-associated pneumonia. METHODS: A multidisciplinary team
      constructed a multifaceted protocol incorporating low risk and low cost
      strategies, many of which had independent advantages of their own. Some
      components were already in use, and their importance was emphasized to improve
      compliance. New strategies included elevation of the head of the bed,
      transpyloric enteral feeding, and antiseptic mouthwash. The approach to
      implementation and maintenance included education, monitoring, audits and
      feedback to encourage compliance with the protocol. RESULTS: The implementation
      of this prevention protocol reduced the incidence of ventilator-associated
      pneumonia from a baseline of 94 cases per year or 26.7 per 1,000 ventilator days
      to 51.3 per year or 12.5 per 1,000 ventilator days, i.e., about 50% of the pre
      protocol rate (P < 0.0001). CONCLUSION: Adherence to simple and effective
      measures can reduce the incidence of ventilator-associated pneumonia. The
      protocol described was inexpensive and effective, and estimated savings are
      large. Implementation and maintenance of gains require a multidisciplinary
      approach, with buy-in from all team members, and ongoing monitoring, education,
      and feedback to the participants.

PMID- 15872135
TI  - Best evidence in critical care medicine: medical therapy of acute colonic pseudo
      obstruction: a moving experience.

PMID- 15872136
TI  - Candida albicans lung abscess sensitive to fluconazole and responding only to
      amphotericin B in a non-immunocompromised critically ill patient.

PMID- 15872137
TI  - Reduction of blood product transfusions during liver transplantation.

PMID- 15872138
TI  - The effects of prostaglandin E1 or oral clonidine premedication on blood loss
      during paranasal sinus surgery.

PMID- 15872139
TI  - Supervising fellows and residents in pediatric anesthesia.

PMID- 15872140
TI  - The prevention of pain from injection of propofol by dexmedetomidine and
      comparison with lidocaine.

PMID- 15872141
TI  - 'Patients who sing need to be relaxed'--neuromuscular blockade as a solution for
      air-leaking during intermittent positive pressure ventilation using LMA.

PMID- 15872142
TI  - Endobronchial metastasis: an anesthetic complication?

PMID- 15872143
TI  - Bilateral foot drop following lower limb orthopedic surgery under spinal
      anesthesia.

PMID- 15872144
TI  - Desflurane costs in ambulatory anesthesia.

PMID- 15872145
TI  - Absence of pulse and blood pressure following vasopressin injection for
      myomectomy.

PMID- 15872146
TI  - Medullary taste responses are modulated by the bed nucleus of the stria
      terminalis.
AB  - Previous studies have shown a modulatory influence of limbic forebrain areas,
      such as the central nucleus of the amygdala and lateral hypothalamus, on the
      activity of taste-responsive cells in the nucleus of the solitary tract (NST).
      The bed nucleus of the stria terminalis (BST), which receives gustatory afferent
      information, also sends descending axons to the NST. The present studies were
      designed to investigate the role of the BST in the modulation of NST gustatory
      activity. Extracellular action potentials were recorded from 101 taste-responsive
      cells in the NST of urethane-anesthetized hamsters and analyzed for a change in
      excitability following bilateral electrical stimulation of the BST. The response
      of NST taste cells to stimulation of the BST was predominately inhibitory.
      Orthodromic inhibitory responses were observed in 29 of 101 (28.7%) NST taste
      responsive cells, with four cells inhibited bilaterally. An increase in
      excitability was observed in seven of the 101 (6.9%) NST taste cells. Of the 34
      cells showing these responses, 25 were modulated by the ipsilateral BST and 15 by
      the contralateral; four were inhibited bilaterally and two inhibited
      ipsilaterally and excited contralaterally. The duration of inhibitory responses
      (mean = 177.9 ms) was significantly longer than that of excitatory responses
      (35.4 ms). Application of subthreshold electrical stimulation to the BST during
      taste trials inhibited or excited the taste responses of every BST-responsive NST
      cell tested with this protocol. NST neurons that were most responsive to sucrose,
      NaCl, citric acid or quinine hydrochloride were all affected by BST stimulation,
      although citric acid-best cells were significantly more often modulated and NaCl
      best less often modulated than expected by chance. These results combine with
      excitatory and inhibitory modulation of NST neurons by the insular cortex,
      lateral hypothalamus and central nucleus of the amygdala to demonstrate extensive
      centrifugal modulation of brainstem gustatory neurons.

PMID- 15872147
TI  - The impact on health-related quality of life from non-steroidal anti-inflammatory
      drugs, methotrexate, or steroids in treatment for juvenile idiopathic arthritis.
AB  - OBJECTIVE: To assess and compare the impact of medication treatments on health
      related quality of life (HRQOL), family function, and medical status in children
      with juvenile idiopathic arthritis (JIA). METHODS: Fifty-seven children diagnosed
      with JIA were assessed by a pediatric rheumatologist and placed into one of three
      treatment groups: (1) non-steroidal anti-inflammatory; (2) methotrexate; or (3)
      steroids via IV methylprednisolone. Questionnaires were administered at baseline
      and 4-month follow-up. The attending pediatric rheumatologist provided additional
      medical information. RESULTS: Data document the impact of JIA on HRQOL,
      particularly on physical and pain domains. Steroid patients experienced improved
      HRQOL at follow-up relative to other groups, despite reporting more problems with
      side effects. CONCLUSION: These results demonstrate positive benefits of steroids
      in treating JIA children, despite the greatest incidence of adverse side effects.

PMID- 15872148
TI  - Ethnicity, ethics, and the deaf-world.
AB  - This article is concerned with ethical aspects of the relations between language
      minorities using signed languages (called the Deaf-World) and the larger
      societies that engulf them. The article aims to show that such minorities have
      the properties of ethnic groups, and that an unsuitable construction of the Deaf
      World as a disability group has led to programs of the majority that discourage
      Deaf children from acquiring the language and culture of the Deaf-World and that
      aim to reduce the number of Deaf births-programs that are unethical from an
      ethnic group perspective. Four reasons not to construe the Deaf-World as a
      disability group are advanced: Deaf people themselves do not believe they have a
      disability; the disability construction brings with it needless medical and
      surgical risks for the Deaf child; it also endangers the future of the Deaf
      World; finally, the disability construction brings bad solutions to real problems
      because it is predicated on a misunderstanding.

PMID- 15872149
TI  - Production and characterization of a phage-display recombinant antibody against
      carrageenans: evidence for the recognition of a secondary structure of
      carrageenan chains present in red algae tissues.
AB  - We report the isolation, for the first time by phage display, of a scFv
      recombinant antibody called B3 directed against carrageenans, the major sulphated
      polysaccharides of red seaweeds. Immunoassays were used to characterize the
      binding of B3 antibodies toward the three main carrageenan forms (iota, kappa,
      and lambda) differing by their sulfonic ester content and the presence of 3,6
      anhydrogalactose. In enzyme-linked immunoadsorbent assay (ELISA), B3 soluble scFv
      showed a high reactivity towards iota-carrageenan at any titer but, at high titer
      only, recognized also the highly sulfated lambda-form. Surface-adsorbed kappa
      polymers were only recognized in presence of poly-L-lysine (PLL). The replacement
      of Na+ ions by K+ in the buffers had no effect on kappa-polymer detection but
      increased the binding of B3 antibodies toward both iota- and lambda-carrageenans,
      whereas addition of Ca2+ decreased sharply the recognition of the iota-form. In
      competitive assays, low titer B3 soluble scFv showed a iota>kappa>lambda
      selectivity and recognized a mixture of iota-oligomers with degrees of
      polymerization between 4 and 18 but not sub-fractions of 4 or 6 residues long. We
      suggest therefore that the B3 epitope could consist of a helical conformation of
      carrageenan chains. Immunofluorescence microscopy showed that, amongst other red
      algae, Chondrus gametophyte (containing iota-chains) was strongly recognized by
      B3 scFv whereas sporophytic tissues rich in lambda-carrageenans were not,
      assessing the preference of this probe for iota-carrageenans in situ. The high
      potential of the B3 recombinant probe is discussed.

PMID- 15872150
TI  - Polysialic acid facilitates tumor invasion by glioma cells.
AB  - Polysialic acid (PSA) is thought to attenuate neural cell adhesion molecule
      (NCAM) adhesion, thereby facilitating neural cell migration and regeneration.
      Although the expression of PSA has been shown to correlate with the progression
      of certain tumors such as small cell lung carcinoma, there have been no studies
      to determine the roles of PSA in gliomas, the most common type of primary brain
      tumor in humans. In this study, we first revealed that among patients with
      glioma, PSA was detected more frequently in diffuse astrocytoma cells, which
      spread extensively. To determine directly the role of PSA in glioma cell
      invasion, we transfected C6 glioma cells with polysialyltransferases to express
      PSA. In those transfected cells, PSA is attached mainly to NCAM-140, whereas the
      mock-transfected C6 cells express equivalent amounts of PSA-free NCAM-140. Both
      PSA negative and positive C6 cell lines exhibited almost identical growth rates
      measured in vitro. However, PSA positive C6 cells exhibited increased invasion to
      the corpus callosum, where the mock-transfected C6 glioma cells rarely invaded
      when inoculated into the brain. By contrast, the invasion to the corpus callosum
      by both the mock-transfected and PSA positive C6 cells was observed in NCAM
      deficient mice. These results combined indicate that PSA facilitates tumor
      invasion of glioma in the brain, and that NCAM-NCAM interaction is likely
      attenuated in the PSA-mediated tumor invasion.

PMID- 15872151
TI  - Photoswitchable cluster glycosides as tools to probe carbohydrate-protein
      interactions: synthesis and lectin-binding studies of azobenzene containing
      multivalent sugar ligands.
AB  - Synthetic cluster glycosides have often been used to unravel mechanisms of
      carbohydrate-protein interactions. Although synthetic cluster glycosides are
      constituted on scaffolds to achieve high avidities in lectin binding, there have
      been no known attempts to modulate the orientations of the sugar clusters with
      the aid of a functional scaffold onto which the sugar units are linked. Herein,
      we describe synthesis, physical, and lectin-binding studies of a series of alpha
      D-mannopyranoside and beta-D-galactopyranosyl-(1-->4)-beta-D-glucopyranoside
      glycoclusters that are attached to a photoswitchable azobenzenoid core. These
      glycoclusters were synthesized by the amidation of amine-tethered
      glycopyranosides with azobenzene carbonyl chlorides. From kinetic studies, the
      cis forms of the azobenzene-glycopyranoside derivative were found to be more
      stable in aqueous solutions than in organic solvents. Molecular modeling studies
      were performed to estimate the relative geometries of the photoswitchable
      glycoclusters in the trans- and cis-isomeric forms. Isothermal titration
      calorimetry (ITC) was employed to assess the binding of these glycoclusters to
      lectins peanut agglutinin (PNA) and concanavalin A (Con A). Although binding
      affinities were enhanced several orders higher as the valency of the sugar was
      increased, a biphasic-binding profile in ITC plots was observed during few
      glycoclusters lectin-binding processes. The biphasic-binding profile indicates a
      "cooperativity" in the binding process. An important outcome of this study is
      that in addition to inherent clustering of the sugar units as a molecular
      feature, an induced clustering emanates because of the isomerization of the trans
      form of the azobenzene scaffold to the cis-isomeric form.

PMID- 15872152
TI  - Imagery-induced cortical excitability changes in stroke: a transcranial magnetic
      stimulation study.
AB  - Focal transcranial magnetic stimulation (TMS) was employed in a population of
      hemiparetic stroke patients in a post-acute stage to map out the abductor digiti
      minimi (ADM) muscle cortical representation of the affected (AH) and unaffected
      (UH) hemisphere at rest, during motor imagery and during voluntary contraction.
      Imagery induced an enhancement of the ADM map area and volume in both hemispheres
      in a way which partly corrected the abnormal asymmetry between AH and UH motor
      output seen in rest condition. The voluntary contraction was the task provoking
      maximal facilitation in the UH, whereas a similar degree of facilitation was
      obtained during voluntary contraction and motor imagery in the AH. We argued that
      motor imagery could induce a pronounced motor output enhancement in the
      hemisphere affected by stroke. Further, we demonstrated that imagery-induced
      excitability changes were specific for the muscle 'prime mover' for the imagined
      movement, while no differences were observed with respect to the stroke lesion
      locations. Present findings demonstrated that motor imagery significantly
      enhanced the cortical excitability of the hemisphere affected by stroke in a post
      acute stage. Further studies are needed to correlate these cortical excitability
      changes with short-term plasticity therefore prompting motor imagery as a
      'cortical reservoir' in post-stroke motor rehabilitation.

PMID- 15872153
TI  - Morphology, electrophysiology and functional input connectivity of pyramidal
      neurons characterizes a genuine layer va in the primary somatosensory cortex.
AB  - Cortical layer V classically has been subdivided into sublayers Va and Vb on
      cytoarchitectonic grounds. In the analysis of cortical microcircuits, however,
      layer Va has largely been ignored. The purpose of this study was to investigate
      pyramidal neurons of layer Va in view of their potential role in integrating
      information from lemniscal and paralemniscal sources. For this we combined
      detailed electrophysiological and morphological characterization with mapping of
      intracortical functional connectivity by caged glutamate photolysis in layer Va
      of rat barrel cortex in vitro. Electrophysiological characterization revealed
      pyramidal cells of the regular spiking as well as the intrinsically burst firing
      type. However, all layer Va pyramidal neurons displayed uniform morphological
      properties and comparable functional input connectivity patterns. They received
      most of their excitatory and inhibitory inputs from intracolumnar sources,
      especially from layer Va itself, but also from layer IV. Those two layers were
      also the main origin for transcolumnar excitatory inputs. Layer Va pyramidal
      neurons thus may predominantly integrate information intralaminarly as well as
      from layer IV. The functional connectivity maps clearly distinguish layer Va from
      layer Vb pyramidal cells, and suggest that layer Va plays a unique role in
      intracortical processing of sensory information.

PMID- 15872154
TI  - Mirror-like spread of chronic pain.
AB  - The spread of chronic pain from its initial site of presentation is common, but
      the mechanisms of the spread are unknown. Here the authors present
      neurophysiologic evidence of altered interhemispheric conduction in a patient
      with a mirror-like spread of complex regional pain syndrome symptoms.

PMID- 15872155
TI  - NKp30 (NCR3) is a pseudogene in 12 inbred and wild mouse strains, but an
      expressed gene in Mus caroli.
AB  - Ancient duplications and rearrangements of protein-coding segments have resulted
      in complex gene family relationships. As a result, gene products may acquire new
      specificities, altered recognition properties, modified functions, and even loss
      of functionality. The natural cytotoxicity receptor (NCR) family are natural
      killer (NK)-activating receptors whose members are NKp46 (NCR1), NKp44 (NCR2),
      and NKp30 (NCR3). The NCR proteins are putative immunoglobulin superfamily
      members whose ligands are unknown. The NKp46 gene is present and expressed in
      human and mouse, NKp44 is only present and expressed in human, and NKp30 is
      present and expressed in human but is a nonexpressed pseudogene in mouse. By
      searching databases we have detected alternatively spliced forms of the three NCR
      members. In addition, we have shown by reverse transcription-polymerase chain
      reaction (RT-PCR) analysis that the human NKp30 gene presents differential
      expression patterns in tissues. However, no expressed sequence tags (ESTs) are
      detected for mouse NKp30, and the genomic sequence contains two premature stop
      codons, which would encode a severely truncated nonfunctional protein. We have
      sequenced genomic DNA from 13 mouse inbred and wild strains and discovered that
      NKp30 is a pseudogene in every mouse strain sequenced except Mus caroli where two
      single nucleotide polymorphisms (SNPs) abolished the premature stop codons. We
      observed that the laboratory-inbred strains are, for the exonic sequences,
      genetically identical, except Mus m. musculus C3H. The Mus musculus strains only
      have a few SNPs, but the rest of the Mus strains have accumulated gradually
      several SNPs, mainly in the functional immunoglobulin and intracellular domains.
      RT-PCR analysis performed on RNA from M. caroli tissue samples identified two
      transcripts, one of which would encode a putative soluble NKp30 protein, also
      detected in rat but not in human. We have observed that the intracellular domains
      of NKp30 (and NKp46) are not conserved among the different species, with the most
      striking difference when comparing human against mouse and rat. The NKp44 gene is
      only found in human and shows three different splice forms varying in their
      "stalk" and intracellular domains. Searching for NKp44 orthologs, we found
      similarity to ESTs from a novel rodent TREM family member, which we termed TREM6,
      and not to any possible NKp44 ortholog.

PMID- 15872157
TI  - Advance directives: stigma strikes again.

PMID- 15872156
TI  - Unique tRNA introns of an enslaved algal cell.
AB  - Nucleomorphs are remnant nuclei of eukaryotic, secondary endosymbionts
      exclusively found in cryptophytes and chlorarachniophytes. The nucleomorph of the
      cryptophyte Guillardia theta codes for 36 transfer RNA (tRNA) genes, 15 of them
      predicted to contain introns and 1 pseudo-tRNA. Some of the predicted intervening
      sequences are manifested at positions not known in Eukarya, even tRNAs with more
      than one intron were suggested. By isolating reverse transcriptase-polymerase
      chain reaction products of the spliced tRNAs we verify the processing of all
      predicted intron-harboring tRNAs and demonstrate the splicing of the smallest
      introns (3 nt) investigated so far. However, the spliced intervening sequences
      are in some cases shifted in respect to the predicted ones. Moreover, we show
      that introns, if inserted into the B-box of tRNA genes in the nucleomorph of
      cryptophytes, mimic promoter regions and do not abolish transcription by RNA
      polymerase III. Consequently, internal nucleomorph-encoded tRNA promoter regions
      are in some cases dissected from the sequence of the mature tRNAs. By reanalyzing
      tRNA introns of a recently sequenced red algae we furthermore show that splicing
      of introns at unusual positions may be introduced in cryptophytes by its
      secondary endosymbiont. However, in contrast to the rest of the symbiont genome,
      introns are not minimized in quantity but are instead scattered along the tRNA
      genes.

PMID- 15872158
TI  - Recent trends in suicide among U.S. adolescent males, 1992-2001.

PMID- 15872159
TI  - Evaluating health care systems.

PMID- 15872160
TI  - The role of services researchers in facilitating intervention research.
AB  - Even when interventions are shown to be both clinically effective and cost
      effective within a system of care, they are rarely sustained beyond the period of
      external funding. The reason may be that these interventions are often developed
      and introduced in a "top-down" manner, with little input from frontline
      clinicians. The purpose of this article is to describe a "bottom-up" approach in
      which services researchers assist frontline clinicians in testing interventions
      that clinicians themselves have devised. This approach is explored in the
      clinical partnership program developed by the Veterans Healthcare
      Administration's South Central Mental Illness Research, Education, and Clinical
      Center. The program is expected to expand the evaluation and research capacity of
      clinicians, enhance the collaborative skills of services researchers, and result
      in interventions that are more likely to be sustained over time.

PMID- 15872161
TI  - Medicine-based evidence in mental health.

PMID- 15872162
TI  - How adolescents perceive the stigma of mental illness and alcohol abuse.
AB  - OBJECTIVES: Research among adults has yielded three sets of conclusions about the
      stigma of mental illness. First, people with mental illness are stigmatized more
      severely than those with physical health conditions; those who abuse alcohol are
      viewed more harshly than those with mental illness. Second, stereotypes of mental
      illness related to responsibility and dangerousness lead to negative emotional
      reactions and discriminatory behaviors. Third, familiarity with people with
      mental illness tends to diminish stigma. This study attempted to validate these
      findings with a large and diverse sample of adolescents. METHODS: A total of 303
      adolescents completed a revised version of the Attribution Questionnaire (rAQ)
      that presented four vignettes, each describing a different type of peer: a peer
      with mental illness, with mental illness caused by a brain tumor, with alcohol
      abuse problems, and with leukemia. The rAQ comprises seven Likert scale items of
      agreement that research participants rated for each vignette. Items included
      pity, danger, fear, responsibility, anger, help, and avoidance. Participants also
      completed a revised Level of Contact Report to assess their familiarity with
      mental illness. RESULTS: As with adults, adolescents stigmatized peers who abuse
      alcohol most severely, followed by those with mental illness. Peers with leukemia
      were treated more benignly than the other groups. Having a brain tumor mediated
      the stigmatizing effect of mental illness. Adolescents who agreed that persons
      with mental illness are responsible for their illness and are dangerous
      demonstrated more discrimination toward these persons. However, this finding was
      not supported for alcohol abuse. Familiarity yielded an unexpected effect among
      adolescents; those who reported more familiarity with mental illness were more
      likely to endorse stigma of mental illness. CONCLUSIONS: Adolescents tended to
      discriminate among conditions, viewing substance abuse more harshly than the
      other disorders. Blame and dangerousness were important variables leading to
      discrimination, and contact with persons with mental illness led to more
      discrimination.

PMID- 15872163
TI  - Newspaper stories as measures of structural stigma.
AB  - OBJECTIVES: Structural stigma and discrimination occur when an institution like a
      newspaper, rather than an individual, promulgates stigmatizing messages about
      mental illness. This study examined current trends in the news media on reporting
      topics of mental illness. METHODS: All relevant stories (N=3,353) in large U.S.
      newspapers were identified and coded during six weeklong periods in 2002. Stories
      were coded by themes that fit into four categories: dangerousness, blame,
      treatment and recovery, and advocacy action (that is, calls for public policy and
      action that increase the quality of care or opportunities for those with mental
      illness). RESULTS: Thirty-nine percent of all stories focused on dangerousness
      and violence; these stories most often ended up in the front section. Few stories
      promulgated the idea that either the person or the family was responsible for
      mental illness (2 percent). Instead, stories about genetic or biological or
      environmental causation (for example, stress and trauma) were more common (15
      percent). There were equal numbers of stories about biological and psychosocial
      treatments (13 and 14 percent, respectively). Four percent of all treatment
      related stories addressed recovery. Twenty percent of stories contained themes
      that fell into the broad category of advocacy action. These stories addressed the
      shortage of resources in the public mental health arena, the need for better
      care, the absence of good-quality housing, and the goal of insurance parity.
      CONCLUSIONS: Data on how mental illness is represented in newspapers yield a
      useful perspective on structural stigma and the policies and standards that are
      applied by the news media. These findings have implications for influencing the
      press.

PMID- 15872164
TI  - Structural stigma in state legislation.
AB  - OBJECTIVE: This article discusses examples of structural stigma that results from
      state governments' enactment of laws that diminish the opportunities of people
      with mental illness. METHODS: To examine current trends in structural stigma, the
      authors identified and coded all relevant bills introduced in 2002 in the 50
      states. Bills were categorized in terms of their effect on liberties, protection
      from discrimination, and privacy. The terms used to describe the targets of bills
      were examined: persons with "mental illness" or persons who are "incompetent" or
      "disabled" because of mental illness. RESULTS: About one-quarter of the state
      bills reviewed for this survey related to protection from discrimination. Within
      that category, half the bills reduced protections for the targeted individuals,
      such as restriction of firearms for people with current or past mental illness
      and reduced parental rights among persons with a history of mental illness. Half
      the bills seemed to expand protections, such as those that required mental health
      funding at the same levels provided for other medical conditions and those that
      disallowed use of mental health status in child custody cases. Legislation
      frequently confuses "incompetence" with "mental illness." CONCLUSIONS: Examples
      of structural stigma uncovered by surveys such as this one can inform advocates
      for persons with mental illness as to where an individual state stands in
      relation to the number of bills that affect persons with mental illness and
      whether these bills expand or contract the liberties of this stigmatized group.

PMID- 15872165
TI  - Effects of caregivers' perceived stigma and causal beliefs on patients' adherence
      to antidepressant treatment.
AB  - OBJECTIVE: Nonadherence to prescribed medications is a significant problem in the
      treatment of mood disorders. Previously proposed adherence models have not been
      sufficiently accurate in identifying patients who do not adhere to treatment.
      This study evaluated the importance of the social context in adherence by using a
      prospective, longitudinal analysis. Specifically, this study evaluated the
      effects of caregivers' causal beliefs about depression and their perceptions of
      stigma on three-month treatment adherence among patients with depression.
      METHODS: Fifty patients with major depressive disorder and their primary
      caregivers were identified at a psychiatric hospital's outpatient clinic.
      Attributions for the causes of depression (either cognitive and attitudinal or
      medical and biological) and perceived stigma were assessed among caregivers at
      baseline, and patients' adherence was evaluated three-months after treatment
      began. RESULTS: Data were available for 47 patients at follow-up. Caregivers'
      attribution of depression to cognitive and attitudinal problems significantly
      predicted patients' decreased adherence. However, the degree of patients'
      adherence was not predicted by caregivers' attributions to medical and biological
      causes and caregivers' perceived stigma. CONCLUSIONS: The findings stress the
      importance of patients' social environment in determining treatment adherence and
      the necessity of educating caregivers about the impact that their causal
      attributions have on patients' behavior. Involving caregivers in treatment may
      improve their attitude toward patients with depression and, in doing so, enhance
      patients' adherence and outcome.

PMID- 15872166
TI  - Local projects of the world psychiatric association programme to reduce stigma
      and discrimination.
AB  - The World Psychiatric Association Programme to Reduce Stigma and Discrimination
      Because of Schizophrenia, which was launched in 1996, has established projects to
      fight stigma in 20 countries, using social-marketing techniques to enhance their
      effectiveness. This article describes some of the strategies used and the lessons
      learned in implementing two local antistigma projects. At each site the first
      steps were to establish an action committee and to conduct a local survey of
      perceived stigma. On the basis of the survey, the local action committee selected
      a few homogeneous and accessible target groups, such as students, employers, and
      criminal justice personnel. These smaller groups were targeted, because focusing
      on the general public is expensive and unlikely to have a measurable impact.
      Messages for the target groups and the media used to reach them were carefully
      selected, tested, and refined. The author gives examples of the work that was
      done with such target groups as high school students and the criminal justice
      system. Guidelines are provided for setting up a consumer speakers' bureau, which
      is valuable for addressing target groups. The bureau can be made up of people who
      have experienced mental illness, family members, and mental health professionals.
      Guidelines are also provided for establishing a media-watch organization, which
      can lobby news and entertainment media to exclude negative portrayals of people
      with mental illness. Organizers of local projects should be on the lookout for
      useful changes that can become permanent, such as changes in the curriculum for
      high school students or for police officers in training. Projects such as these
      can be effective in reducing stigma and can be relatively inexpensive.

PMID- 15872167
TI  - Medical advance care planning for persons with serious mental illness.
AB  - OBJECTIVE: This study examined preferences regarding medical advance care
      planning among persons with serious mental illness, specifically, experience,
      beliefs, values, and concerns about health care proxies and end-of-life issues.
      METHODS: A structured interview, the Health Care Preferences Questionnaire, was
      administered to a convenience sample of 150 adults with serious mental illness
      who were receiving community-based services from the Massachusetts Department of
      Mental Health. Clinical information and demographic data were also collected.
      RESULTS: A total of 142 participants completed the questionnaire. Although more
      than one-quarter had thought about their medical treatment preferences in the
      event that they became seriously medically ill, very few had discussed these
      preferences. A majority of respondents (72 percent) believed that someone should
      be designated to make medical health care decisions for a person who is too sick
      to make or communicate these decisions him- or herself. Common end-of-life
      concerns included financial and emotional burdens on family, pain and suffering,
      interpersonal issues such as saying "goodbye," spiritual issues, and funeral
      arrangements. Participants were most uneasy about the prolonging or stopping of
      life support by proxy decision makers. A total of 104 respondents (69 percent)
      expressed interest in formally selecting a health care proxy. CONCLUSIONS:
      Although persons with serious and persistent mental illness have little
      experience with medical advance care planning, they show substantial interest in
      it. Furthermore, they are able to consider and communicate their preferences.
      This study supports the feasibility, acceptability, and utility of a standardized
      approach to medical advance care planning with this population.

PMID- 15872168
TI  - End-of-life treatment preferences of persons with serious mental illness.
AB  - OBJECTIVE: The goal of this study was to ascertain preferences for end-of-life
      care among persons with serious mental illness. METHODS: The participants were
      150 community-residing adults with serious mental illness. The Health Care
      Preferences Questionnaire was administered to obtain information about treatment
      preferences in response to hypothetical medical illness scenarios: use of pain
      medication in the case of incurable cancer and use of artificial life support in
      the case of irreversible coma. Participants were asked what their treatment
      preferences would be for an imaginary person in each scenario ("other") as well
      as their preferences for themselves ("self"). RESULTS: For the scenario involving
      pain medication for incurable cancer, most participants chose aggressive pain
      management even if cognition might be affected (64 percent of respondents under
      the "other" scenario and 66 percent under the "self" scenario). Few participants
      thought a doctor should provide patients with enough medication to end their life
      (34 percent for self and 24 percent for other). For the scenario involving
      irreversible coma, respondents were divided in their choice regarding life
      support. Approximately one-quarter said that they would prefer to immediately
      terminate life support (28 percent of respondents for other and 29 percent for
      self), and half said they would choose to turn it off after a defined period (48
      percent for other and 45 percent for self). CONCLUSIONS: Persons with serious
      mental illness were able to designate treatment preferences in response to end-of
      life health state scenarios. Future research is needed to test advance care
      planning methods, assess stability of choices over time, and ascertain the
      utility of scenario-based preferences to guide end-of-life care decisions in this
      population.

PMID- 15872169
TI  - The content and clinical utility of psychiatric advance directives.
AB  - OBJECTIVE: This paper provides the first systematic examination of the content
      and clinical utility of psychiatric advance directives, which are documents that
      specify treatment preferences in advance of periods of compromised decision
      making. METHODS: Directives were completed by 106 community mental health center
      outpatients with at least two psychiatric hospitalizations or emergency
      department visits within two years. Participants used AD-Maker software in groups
      of up to six people led by peer trainers. Clinical utility was defined as the
      degree to which instructions are clinically feasible, useful, and consistent with
      standards of care. RESULTS: Fifty-five percent of participants were female, and
      24 percent were nonwhite. Their mean+/-SD age was 42+/-9.1 years. Primary
      diagnoses included schizophrenia spectrum disorders (44 percent), bipolar
      disorders (27 percent), major depression (22 percent), and other disorders (7
      percent). Eighty-one percent of participants listed preferred medications, most
      often antidepressants and second-generation antipsychotics, and 64 percent listed
      medications they would refuse, most commonly first-generation antipsychotics.
      Sixty-eight percent preferred hospital alternatives over hospitalization, 89
      percent specified methods of de-escalating crises, and 72 percent indicated that
      they would refuse electroconvulsive therapy (ECT). Forty-six percent appointed a
      surrogate decision maker. Fifty-seven percent desired a directive that is
      irrevocable during periods of incapacity. Instructions were rated as feasible,
      useful, and consistent with practice standards for at least 95 percent of the
      advance directives, with the exception of instructions about the willingness to
      use medications not specifically listed in the directive. CONCLUSIONS: Results
      suggested that psychiatric advance directives provide a wealth of treatment
      preference information that is almost uniformly considered clinically useful.
      Although the utility of advance directives may vary depending on the
      circumstances of specific crisis episodes, the information provided can expedite
      and strengthen clinical care.

PMID- 15872170
TI  - Self-stigma and its correlates among outpatients with depressive disorders.
AB  - The aims of this study were to assess self-stigma among Taiwanese outpatients
      with depressive disorders and to examine the factors related to self-stigma.
      Using the Self-Stigma Assessment Scale, the authors evaluated 247 outpatients
      with depressive disorders to determine their levels of self-stigma. The
      relationships between self-stigma and severity of depressive symptoms,
      sociodemographic characteristics, and course of illness were further examined.
      Sixty-two patients (25 percent) had high levels of self-stigma. Patients who had
      more severe depression and less education had higher levels of self-stigma.
      Clinicians should take self-stigma into consideration when communicating with
      depressed patients, especially those with characteristics associated with high
      levels of self-stigma.

PMID- 15872171
TI  - Factors associated with a positive response to cognitive remediation in a
      community psychiatric sample.
AB  - This study examined some of the factors associated with a positive response to
      cognitive remediation. Forty-eight adult participants completed 26 hours of
      cognitive skills training at an outpatient psychiatric clinic. Results showed
      significant posttreatment improvement on measures of sustained attention and
      readiness for employment. Notably, participant-determined attendance was
      associated with greater cognitive improvement. In addition, there was a threshold
      of treatment intensity below which there was no treatment effect. This study
      underscores the importance of addressing treatment intensity in the
      implementation of cognitive remediation in the community and highlights the
      potential contribution of motivation to treatment adherence.

PMID- 15872172
TI  - A survey of mental health leaders one year after the President's New Freedom
      Commission report.
AB  - As part of the 19th annual Rosalynn Carter Symposium on Mental Health Policy,
      held in 2003, an anonymous online survey of symposium participants was conducted
      to gain insight into participants' perceptions of the impact on their
      organizations of the President's New Freedom Commission and its recommendations.
      The participants were national mental health leaders representing a broad range
      of mental health agencies and organizations. The results of the survey suggest
      that the New Freedom Commission has had a substantial impact on the organizations
      represented at the symposium. Findings on successes and challenges in
      implementing the recommendations suggest areas for ongoing efforts to transform
      mental health care.

PMID- 15872173
TI  - Community psychiatry and medical student education.

PMID- 15872174
TI  - A day hospital for adults with intellectual disabilities and psychiatric
      disorders.

PMID- 15872175
TI  - Best friends of people with mental illness and mental retardation.

PMID- 15872176
TI  - Are mental health professionals immune to stigmatizing beliefs?

PMID- 15872177
TI  - Closing the gap in evaluation technology for outcomes monitoring.

PMID- 15872179
TI  - Psychotherapy and eclecticism.

PMID- 15872180
TI  - Modern times and quality of care.

PMID- 15872181
TI  - Missed Monday appointments.

PMID- 15872182
TI  - The poly(A)-limiting element enhances mRNA accumulation by increasing the
      efficiency of pre-mRNA 3' processing.
AB  - The poly(A)-limiting element (PLE) is a conserved sequence originally found in
      the 3' UTR of Xenopus albumin mRNA whose presence restricts the length of the
      poly(A) tail on both pre-mRNA and fully processed mRNA to <20 nt. Results
      presented in this study show that the PLE also increases the cytoplasmic level of
      reporter beta-globin mRNA. Transcription run-on shows this increase was not due
      to increased reporter gene transcription, and experiments with tetracycline
      repressor-controlled reporter mRNA showed the PLE does not alter the rate of mRNA
      decay. Both RT-PCR and RNase protection assay showed the PLE caused a 50%
      increase in the 3' processing of reporter beta-globin mRNA in vivo. This was
      confirmed in vitro, where PLE-containing RNA was cleaved in HeLa nuclear extract
      at a rate 80% faster than a control RNA bearing an inactive element. These
      results indicate that the PLE regulates the length of the poly(A) tail and the
      efficiency of 3' processing. In addition, they show that PLE-containing mRNA with
      a <20-nt poly(A) tail is as stable as mRNA with a 100- to 200-nt poly(A) tail.

PMID- 15872183
TI  - In vivo excision of a single targeted nucleotide from an mRNA by a trans excision
      splicing ribozyme.
AB  - We have previously reported the development of a group I intron-derived ribozyme
      that can bind an exogenous RNA substrate and excise from that substrate an
      internal segment in vitro, which allows for sequence-specific modification of RNA
      molecules. In this report, the activity of this trans excision-splicing ribozyme
      in a cellular environment, specifically Escherichia coli, was investigated. The
      ribozyme was re-engineered to target for excision a single-base insertion in the
      transcript of a green fluorescent protein, and fluorescence was exploited as a
      reporter for trans excision-splicing. We show that the ribozyme is able to
      catalyze the trans excision-splicing reaction in vivo and can repair the mutant
      transcripts. On average, 12% correction is observed as measured by fluorescence
      and at least 0.6% correction as confirmed through sequence analysis. This
      represents the first report of a biomolecule (in this case a ribozyme) that can
      selectively excise a targeted nucleotide from within an mRNA transcript in vivo.
      This new class of biochemical tools makes possible a wide variety of new
      experimental strategies, perhaps including a new approach to molecular-based
      therapeutics.

PMID- 15872184
TI  - A functional relationship between helix 1 and the 900 tetraloop of 16S ribosomal
      RNA within the bacterial ribosome.
AB  - The conserved 900 tetraloop that caps helix 27 of 16S ribosomal RNA (rRNA)
      interacts with helix 24 of 16S rRNA and also with helix 67 of 23S rRNA, forming
      the intersubunit bridge B2c, proximal to the decoding center. In previous
      studies, we investigated how the interaction between the 900 tetraloop and helix
      24 participates in subunit association and translational fidelity. In the present
      study, we investigated whether the 900 tetraloop is involved in other undetected
      interactions with different regions of the Escherichia coli 16S rRNA. Using a
      genetic complementation approach, we selected mutations in 16S rRNA that
      compensate for a 900 tetraloop mutation, A900G, which severely impairs subunit
      association and translational fidelity. Mutations were randomly introduced in 16S
      rRNA, using either a mutagenic XL1-Red E. coli strain or an error-prone PCR
      strategy. Gain-offunction mutations were selected in vivo with a specialized
      ribosome system. Two mutations, the deletion of U12 and the U12C substitution,
      were thus independently selected in helix 1 of 16S rRNA. This helix is located in
      the vicinity of helix 27, but does not directly contact the 900 tetraloop in the
      crystal structures of the ribosome. Both mutations correct the subunit
      association and translational fidelity defects caused by the A900G mutation,
      revealing an unanticipated functional interaction between these two regions of
      16S rRNA.

PMID- 15872185
TI  - Human mitochondrial tRNAMet is exported to the cytoplasm and associates with the
      Argonaute 2 protein.
AB  - Argonaute (Ago) proteins are the effector proteins of RNA interference (RNAi) and
      related silencing mechanisms that are mediated by small RNAs. Ago proteins bind
      directly to microRNAs (miRNAs) and to short interfering RNAs and are the core
      protein components of RNA induced silencing complexes (RISCs) and microRNPs
      (miRNPs). Here we report that an ~70-nt RNA associates specifically with
      immunopurified Ago2 expressed in human 293 cells. By directional cloning we
      identified this RNA as the mitochondrial tRNA(Met) (mt tRNA(Met)). Various
      exported (mt) tRNAs were detected in the cytosol of 293 cells, but Ago2 was found
      selectively bound to (mt) tRNA(Met). The association in the cytosol of exported
      (mt) tRNA(Met) with Ago2 complements genetic and microscopic data that link
      mitochondria with RNAi-related components and events.

PMID- 15872186
TI  - Translational autocontrol of the Escherichia coli hfq RNA chaperone gene.
AB  - The conserved bacterial RNA chaperone Hfq has been shown to play an important
      role in post-transcriptional regulation. Here, we demonstrate that Hfq synthesis
      is autoregulated at the translational level. We have mapped two Hfq binding sites
      in the 5'-untranslated region of hfq mRNA and show that Hfq binding inhibits
      formation of the translation initiation complex. In vitro translation and in vivo
      studies further revealed that Hfq binding to both sites is required for efficient
      translational repression of hfq mRNA.

PMID- 15872187
TI  - Characterization of conserved sequence elements in eukaryotic RNase P RNA reveals
      roles in holoenzyme assembly and tRNA processing.
AB  - RNase P is a ubiquitous endoribonuclease responsible for cleavage of the 5'
      leader of precursor tRNAs (pre-tRNAs). Although the protein composition of RNase
      P holoenzymes varies significantly among Bacteria, Archaea, and Eukarya, the
      holoenzymes have essential RNA subunits with several sequences and structural
      features that are common to all three kingdoms of life. Additional structural
      elements of the RNA subunits have been found that are conserved in eukaryotes,
      but not in bacteria, and might have functions specifically required by the more
      complex eukaryotic holoenzymes. In this study, we have mutated four eukaryotic
      specific conserved regions in Saccharomyces cerevisiae nuclear RNase P RNA and
      characterized the effects of the mutations on cell growth, enzyme function, and
      biogenesis of RNase P. RNase P with mutations in each of the four regions tested
      is sufficiently functional to support life although growth of the resulting yeast
      strains was compromised to varying extents. Further analysis revealed that
      mutations in three different regions cause differential defects in holoenzyme
      assembly, localization, and pre-tRNA processing in vivo and in vitro. These data
      suggest that most, but not all, eukaryotic-specific conserved regions of RNase P
      RNA are important for the maturation and function of the holoenzyme.

PMID- 15872189
TI  - Increasing breastfeeding rates in New York City, 1980-2000.
AB  - Our objective was to determine temporal patterns of breastfeeding among women
      delivering infants in New York City (NYC) and compare national breastfeeding
      trends. All hospitals in NYC with obstetric units were contacted in May and June
      2000 to provide information on the method of infant feeding during the mother's
      admission for delivery. Feeding was categorized as "exclusive breastfeeding,"
      "breast and formula," or "exclusive formula." The first two categories were
      further grouped into "any breastfeeding" in the analysis. Hospitals were
      classified as "public" and "private," and patients were classified by insurance
      type as "service" and "private." Data between public and private hospitals and
      service and private patients were compared. Breast-feeding trends over time were
      compared by using previous iterations of the same survey. Of 16,932 newborns,
      representing approximately 80.0% of all reported live births in the city during
      the study period, 5,305 (31.3%) were exclusively breastfed, 6,189 (36.6%) were
      fed a combination of breast milk and formula, and the remaining 5,438 (32.1%)
      were exclusively formula-fed. Infants born in private hospitals were 1.6 times
      more likely to be exclusively breastfed compared with infants discharged from
      public hospitals (33% vs. 21%, respectively). Similarly, private patients were
      more likely than service patients to exclusively breastfeed their infants (39.6%
      vs. 22.9%, respectively) and to use a combination of breast and formula (i.e.,
      any breastfeeding) (73.6% vs. 62.0%, respectively). From 1980 to 2000, the
      proportion of exclusive breastfeeding increased from 25.0% to 31.0%, the
      percentage of combined feeding increased from 8.0% to 37.0%, and the percentage
      of any breastfeeding increased from 33.0% to 68.0%. NYC has more than doubled the
      rate of breastfeeding since 1980. However, there is much progress to be made, and
      continued efforts are vital to maintain current gains in breastfeeding, improve
      the rates further, and prolong the duration of breastfeeding.

PMID- 15872188
TI  - Potential uptake and correlates of willingness to use a supervised smoking
      facility for noninjection illicit drug use.
AB  - Many cities are experiencing infectious disease epidemics and substantial
      community harms as a result of illicit drug use. Although medically supervised
      smoking facilities (SSFs) remain untested in North America, local health
      officials in Vancouver are considering to prepare a submission to Health Canada
      for an exemption to open Canada's first SSF for evaluation. Reluctance of health
      policymakers to initiate a pilot study of SSFs may be due in part to outstanding
      questions regarding the potential uptake and community impacts of the
      intervention. This study was conducted to evaluate the prevalence and correlates
      of willingness to use an SSF among illicit drug smokers who are enrolled in the
      Vancouver Injection Drug Users Study. Participants who reported actively smoking
      cocaine, heroin, or methamphetamine who returned for follow-up between June 2002
      and December 2002 were eligible for these analyses. Those who reported
      willingness to use an SSF were compared with those who were unwilling to use an
      SSF by using logistic regression analyses. Four hundred and forty-three
      participants were eligible for this study. Among respondents, 124 (27.99%)
      expressed willingness to attend an SSF. Variables that were independently
      associated with willingness to attend an SSF in multivariate analyses included
      sex-trade work (adjusted odds ratio [AOR]=1.85), crack pipe sharing (AOR=2.24),
      and residing in the city's HIV epicentre (AOR =1.64). We found that participants
      who demonstrated a willingness to attend an SSF were more likely to be involved
      in the sex trade and share crack pipes. Although the impact of SSFs in North
      America can only be quantified by scientific evaluation, these data indicate a
      potential for public health and community benefits if SSFs were to become
      available.

PMID- 15872190
TI  - Correlates of HIV infection among incarcerated women: implications for improving
      detection of HIV infection.
AB  - The prevalence of HIV infection in correctional settings is several-fold higher
      than found in community settings. New approaches to identifying HIV infection
      among prisoners are urgently needed. In order to determine the HIV seroprevalence
      and to identify the correlates of HIV infection among female prisoners, an
      anonymous, but linked HIV serosurvey was conducted at Connecticut's sole
      correctional facility for women (census=1,100). After removing all individual
      identifiers for inmates' standardized clinical and risk behavior information,
      data are linked by a third source to blinded HIV-testing information by a third
      party. This three-step sequential process allows for anonymous HIV testing that
      can still be linked with deidentified clinical and behavioral data. Of the 3,315
      subjects with complete information, 250 (7.5%) were HIV+. Of these, 157 (63%)
      self-reported being HIV+. Using multiple logistic regression analysis, having sex
      with a known HIV+ person [adjusted odds ratio (AOR)=9.1] and injection drug use
      (AOR=6.1) were the most highly correlated risk factors for HIV, whereas
      leukopenia (AOR=9.4) and hypoalbuminemia (AOR=7.2) were the most significant
      laboratory markers. Other independent correlates of HIV included self-report of
      syphilis (AOR=1.9) or genital herpes infection (AOR=2.7) and being Black
      (AOR=2.1) or Hispanic (AOR=2.2). The prevalence of HIV and HIV-risk behaviors is
      high among incarcerated women. Existing voluntary HIV counseling and testing
      programs do not completely target high-risk groups who remain part of the
      evolving epidemic. Defined demographic, behavioral, and clinical assessments may
      provide useful information for encouraging targeted counseling and testing. Newer
      targeted approaches merit further study to determine the effectiveness of this
      approach. Alternative methods of facilitating more widespread HIV testing, such
      as saliva tests, rapid serologic tests, and more routine testing in high HIV
      prevalence areas should be considered both for clinical and for public health
      benefits.

PMID- 15872191
TI  - Acupuncture for substance abuse treatment in the Downtown Eastside of Vancouver.
AB  - In British Columbia, Canada, the City of Vancouver's notorious Downtown Eastside
      (DES) represents the poorest urban population in Canada. A prevalence rate of 30%
      for HIV and 90% for hepatitis C makes this a priority area for public-health
      interventions aimed at reducing the use of injected drugs. This study examined
      the utility of acupuncture treatment in reducing substance use in the
      marginalized, transient population. Acupuncture was offered on a voluntary, drop
      in basis 5 days per week at two community agencies. During a 3-month period, the
      program generated 2,755 client visits. A reduction in overall use of substances
      (P=.01) was reported by subjects in addition to a decrease in intensity of
      withdrawal symptoms including "shakes," stomach cramps, hallucinations, "muddle
      headedness," insomnia, muscle aches, nausea, sweating, heart palpitations, and
      feeling suicidal, P<.05. Acupuncture offered in the context of a community-based
      harm reduction model holds promise as an adjunct therapy for reduction of
      substance use.

PMID- 15872193
TI  - A description of a peer-run supervised injection site for injection drug users.
AB  - Owing to the ongoing health crisis among injection drug users in Vancouver,
      Canada, there have been repeated calls for the establishment of supervised
      injection sites (SIS) since the early 1990s. In April 2003, a group of advocates
      and drug users opened an unsanctioned SIS in Vancouver's Downtown Eastside. The
      "327 SIS" operated for 184 days. During the operation of the SIS, volunteers
      supervised over 3,000 injections by a high-risk injection drug using population.
      The SIS provided a sterile environment for injection drug use without measured
      negative consequences and demonstrated the feasibility of a peer-driven low
      threshold SIS.

PMID- 15872192
TI  - Naloxone distribution and cardiopulmonary resuscitation training for injection
      drug users to prevent heroin overdose death: a pilot intervention study.
AB  - Fatal heroin overdose has become a leading cause of death among injection drug
      users (IDUs). Several recent feasibility studies have concluded that naloxone
      distribution programs for heroin injectors should be implemented to decrease
      heroin over-dose deaths, but there have been no prospective trials of such
      programs in North America. This pilot study was undertaken to investigate the
      safety and feasibility of training injection drug using partners to perform
      cardiopulmonary resuscitation (CPR) and administer naloxone in the event of
      heroin overdose. During May and June 2001, 24 IDUs (12 pairs of injection
      partners) were recruited from street settings in San Francisco. Participants took
      part in 8-hour training in heroin overdose prevention, CPR, and the use of
      naloxone. Following the intervention, participants were prospectively followed
      for 6 months to determine the number and outcomes of witnessed heroin overdoses,
      outcomes of participant interventions, and changes in participants' knowledge of
      overdose and drug use behavior. Study participants witnessed 20 heroin overdose
      events during 6 months follow-up. They performed CPR in 16 (80%) events,
      administered naloxone in 15 (75%) and did one or the other in 19 (95%). All
      overdose victims survived. Knowledge about heroin overdose management increased,
      whereas heroin use decreased. IDUs can be trained to respond to heroin overdose
      emergencies by performing CPR and administering naloxone. Future research is
      needed to evaluate the effectiveness of this peer intervention to prevent fatal
      heroin overdose.

PMID- 15872195
TI  - Images in clinical medicine. Improvement in hypertensive retinopathy after
      treatment of hypertension.

PMID- 15872196
TI  - Preparing for the next pandemic.

PMID- 15872194
TI  - Illicit opioid use in Canada: comparing social, health, and drug use
      characteristics of untreated users in five cities (OPICAN study).
AB  - Most of the estimated 125,000 injection drug users (IDUs) in Canada use illicit
      opioids and are outside treatment (i.e., methadone maintenance treatment).
      Empirical data suggest that illicit opioid users outside treatment are
      characterized by various health and social problem characteristics, including
      polydrug use, physical and mental morbidity, social marginalization, and crime.
      Although required for evidence-based programming, systematic information on this
      specific substance-user population is sparse in Canada to date. This article
      presents and compares key characteristics of population of illicit opioid users
      outside treatment in five cities across Canada (OPICAN cohort). Overall, the
      majority of OPICAN participants regularly used both a variety of illicit opioids
      and cocaine or crack, reported physical and mental health (e.g., mood disorder)
      problems, lacked permanent housing, were involved in crime, and had their "ideal"
      treatment not available to them. However, key local sample differences were
      shown, including patterns of heroin versus prescription opioid use and levels of
      additional cocaine versus crack use as well as indicators of social
      marginalization. Illicit opioid user population across Canada differ on key
      social, health, and drug use indicators that are crucial for interventions and
      are often demonstrated between larger and smaller city sites. Differentiated
      interventions are required.

PMID- 15872197
TI  - Physician as serial killer--the Shipman case.

PMID- 15872198
TI  - The calling.

PMID- 15872199
TI  - Hyperactive vasopressin receptors and disturbed water homeostasis.

PMID- 15872200
TI  - Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer).
AB  - BACKGROUND: Germ-line mutations in the mismatch-repair genes MLH1, MSH2, MSH6,
      and PMS2 lead to the development of the Lynch syndrome (hereditary nonpolyposis
      colorectal cancer), conferring a strong susceptibility to cancer. We assessed the
      frequency of such mutations in patients with colorectal cancer and examined
      strategies for molecular screening to identify patients with the syndrome.
      METHODS: Patients with a new diagnosis of colorectal adenocarcinoma at the major
      hospitals in metropolitan Columbus, Ohio, were eligible for the study. Genotyping
      of the tumor for microsatellite instability was the primary screening method.
      Among patients whose screening results were positive for microsatellite
      instability, we searched for germ-line mutations in the MLH1, MSH2, MSH6, and
      PMS2 genes with the use of immunohistochemical staining for mismatch-repair
      proteins, genomic sequencing, and deletion studies. Family members of carriers of
      the mutations were counseled, and those found to be at risk were offered mutation
      testing. RESULTS: Of 1066 patients enrolled in the study, 208 (19.5 percent) had
      microsatellite instability, and 23 of these patients had a mutation causing the
      Lynch syndrome (2.2 percent). Among the 23 probands with the Lynch syndrome, 10
      were more than 50 years of age and 5 did not meet the Amsterdam criteria or the
      Bethesda guidelines for the diagnosis of hereditary nonpolyposis colorectal
      cancer (including the use of age and family history to identify patients at high
      risk for the Lynch syndrome). Genotyping for microsatellite instability alone and
      immunohistochemical analysis alone each failed to identify two probands. In the
      families of 21 of the probands, 117 persons at risk were tested, and of these, 52
      had Lynch syndrome mutations and 65 did not. CONCLUSIONS: Routine molecular
      screening of patients with colorectal adenocarcinoma for the Lynch syndrome
      identified mutations in patients and their family members that otherwise would
      not have been detected. These data suggest that the effectiveness of screening
      with immunohistochemical analysis of the mismatch-repair proteins would be
      similar to that of the more complex strategy of genotyping for microsatellite
      instability.

PMID- 15872201
TI  - Amiodarone versus sotalol for atrial fibrillation.
AB  - BACKGROUND: The optimal pharmacologic means to restore and maintain sinus rhythm
      in patients with atrial fibrillation remains controversial. METHODS: In this
      double-blind, placebo-controlled trial, we randomly assigned 665 patients who
      were receiving anticoagulants and had persistent atrial fibrillation to receive
      amiodarone (267 patients), sotalol (261 patients), or placebo (137 patients) and
      monitored them for 1 to 4.5 years. The primary end point was the time to
      recurrence of atrial fibrillation beginning on day 28, determined by means of
      weekly transtelephonic monitoring. RESULTS: Spontaneous conversion occurred in
      27.1 percent of the amiodarone group, 24.2 percent of the sotalol group, and 0.8
      percent of the placebo group, and direct-current cardioversion failed in 27.7
      percent, 26.5 percent, and 32.1 percent, respectively. The median times to a
      recurrence of atrial fibrillation were 487 days in the amiodarone group, 74 days
      in the sotalol group, and 6 days in the placebo group according to intention to
      treat and 809, 209, and 13 days, respectively, according to treatment received.
      Amiodarone was superior to sotalol (P<0.001) and to placebo (P<0.001), and
      sotalol was superior to placebo (P<0.001). In patients with ischemic heart
      disease, the median time to a recurrence of atrial fibrillation was 569 days with
      amiodarone therapy and 428 days with sotalol therapy (P=0.53). Restoration and
      maintenance of sinus rhythm significantly improved the quality of life and
      exercise capacity. There were no significant differences in major adverse events
      among the three groups. CONCLUSIONS: Amiodarone and sotalol are equally
      efficacious in converting atrial fibrillation to sinus rhythm. Amiodarone is
      superior for maintaining sinus rhythm, but both drugs have similar efficacy in
      patients with ischemic heart disease. Sustained sinus rhythm is associated with
      an improved quality of life and improved exercise performance.

PMID- 15872202
TI  - Detection of acute infections during HIV testing in North Carolina.
AB  - BACKGROUND: North Carolina has added nucleic acid amplification testing for the
      human immunodeficiency virus (HIV) to standard HIV antibody tests to detect
      persons with acute HIV infection who are viremic but antibody-negative. METHODS:
      To determine the effect of nucleic acid amplification testing on the yield and
      accuracy of HIV detection in public health practice, we conducted a 12-month
      observational study of methods for state-funded HIV testing. We compared the
      diagnostic performance of standard HIV antibody tests (i.e., enzyme immunoassay
      and Western blot analysis) with an algorithm whereby serum samples that yielded
      negative results on standard antibody tests were tested again with the use of
      nucleic acid amplification. A surveillance algorithm with repeated sensitive-less
      sensitive enzyme immunoassay tests was also evaluated. HIV infection was defined
      as a confirmed positive result on a nucleic acid amplification test or as HIV
      antibody seroconversion. RESULTS: Between November 1, 2002, and October 31, 2003,
      109,250 persons at risk for HIV infection who had consented to HIV testing
      presented at state-funded sites. There were 606 HIV-positive results. Established
      infection, as identified by standard enzyme immunoassay or Western blot analysis,
      appeared in 583 participants; of these, 107 were identified, with the use of
      sensitive-less-sensitive enzyme immunoassay tests, as recent infections. A total
      of 23 acutely infected persons were identified only with the use of the nucleic
      acid amplification algorithm. With all detectable infections taken into account,
      the sensitivity of standard antibody testing was 0.962 (95 percent confidence
      interval, 0.944 to 0.976). There were two false positive results on nucleic acid
      amplification tests. The specificity and positive predictive value of the
      algorithm that included nucleic acid amplification testing were greater than
      0.999 (95 percent confidence interval, 0.999 to >0.999) and 0.997 (95 percent
      confidence interval, 0.988 to >0.999), respectively. Of the 23 acute HIV
      infections, 16 were detected at sexually transmitted disease clinics. Emergency
      measures for HIV prevention protected 48 sex partners and one fetus from high
      risk exposure to HIV. CONCLUSIONS: The addition of nucleic acid amplification
      testing to an HIV testing algorithm significantly increases the identification of
      cases of infection without impairing the performance of diagnostic testing. The
      detection of highly contagious, acutely infected persons creates new
      opportunities for HIV surveillance and prevention.

PMID- 15872203
TI  - Nephrogenic syndrome of inappropriate antidiuresis.
AB  - The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common
      cause of hyponatremia. We describe two infants whose clinical and laboratory
      evaluations were consistent with the presence of SIADH, yet who had undetectable
      arginine vasopressin (AVP) levels. We hypothesized that they had gain-of-function
      mutations in the V2 vasopressin receptor (V2R). DNA sequencing of each patient's
      V2R gene (AVPR2) identified missense mutations in both, with resultant changes in
      codon 137 from arginine to cysteine or leucine. These novel mutations cause
      constitutive activation of the receptor and are the likely cause of the patients'
      SIADH-like clinical picture, which we have termed "nephrogenic syndrome of
      inappropriate antidiuresis."

PMID- 15872204
TI  - Clinical practice. Persistent low back pain.

PMID- 15872205
TI  - Psoriasis.

PMID- 15872206
TI  - Images in clinical medicine. Sister Mary Joseph's nodule.

PMID- 15872207
TI  - Clinical problem-solving. Clear as mud.

PMID- 15872208
TI  - Molecular screening for the Lynch syndrome--better than family history?

PMID- 15872209
TI  - Myocardial stunning due to sudden emotional stress.

PMID- 15872210
TI  - Vascular risk factors and diabetic neuropathy.

PMID- 15872211
TI  - Health care in the 21st century.

PMID- 15872212
TI  - Avian influenza and pandemics.

PMID- 15872213
TI  - Cardiac sarcoma 14 years after treatment for pleural mesothelioma.

PMID- 15872214
TI  - Case 4-2005: sodium stibogluconate for cutaneous leishmaniasis.

PMID- 15872215
TI  - Osteoporosis, teriparatide, and dosing of calcium and vitamin D.

PMID- 15872216
TI  - Inhibition of double-strand break non-homologous end-joining by cisplatin adducts
      in human cell extracts.
AB  - The effect of cis-diaminedichloroplatinum(II) (cisplatin) DNA damage on the
      repair of double-strand breaks by non-homologous end-joining (NHEJ) was
      determined using cell-free extracts. NHEJ was dramatically decreased when plasmid
      DNA was damaged to contain multiple types of DNA adducts, along the molecule and
      at the termini, by incubation of DNA with cisplatin; this was a cisplatin
      concentration-dependent effect. We investigated the effect a single GTG
      cisplatination site starting 10 bp from the DNA termini would have when
      surrounded by the regions of AT-rich DNA which were devoid of the major adduct
      target sequences. Cisplatination of a substrate containing short terminal 13-15
      bp AT-rich sequences reduced NHEJ to a greater extent than that of a substrate
      with longer (31-33 bp) AT-rich sequences. However, cisplatination at the single
      GTG site within the AT sequence had no significant effect on NHEJ, owing to the
      influence of additional minor monoadduct and dinucleotide adduct sites within the
      AT-rich region and owing to the influence of cisplatination at sites upstream of
      the AT-rich regions. We then studied the effect on NHEJ of one cis
      [Pt(NH3)2{d(GpTpG)-N7(1),-N7(3)} [abbreviated as 1,3-d(GpTpG)] cisplatin adduct
      in the entire DNA molecule, which is more reflective of the situation in vivo
      during concurrent chemoradiation. The presence of a single 1,3-d(GpTpG) cisplatin
      adduct 10 bases from each of the two DNA ends to be joined resulted in a small
      (30%) but significant decrease in NHEJ efficiency. This process, which was DNA
      dependent protein kinase and Ku dependent, may in part explain the
      radiosensitizing effect of cisplatin administered during concurrent
      chemoradiation.

PMID- 15872217
TI  - Modulating DNA bending affects NodD-mediated transcriptional control in Rhizobium
      leguminosarum.
AB  - Rhizobium leguminosarum NodD binds to the nod box of the inducible nod gene nodA
      as a V-shaped tetramer and bends the nod box. In this work, we show that the nod
      gene inducer naringenin decreased gel mobility of nod box DNA-NodD complexes by
      sharpening the NodD-induced DNA bend, which correlated with nodA transcription
      activation. NodD can induce different DNA bends when the distance between the two
      half-sites of the nod box was modified, which severely affected NodD-mediated
      transcriptional control. One or two base pairs were deleted from, or inserted
      into, the two half-sites of the nod box of nodA. Circular permutation assays
      showed that such distance modulations allowed NodD to induce relaxed or sharpened
      DNA bending. In the case of 1 bp deletion, where the DNA bends were more relaxed
      than in the wild type, nodA transcription was repressed both in the absence and
      in the presence of inducer naringenin. In the cases of 1 and 2 bp insertion,
      where the DNA bends were much sharper than in wild type in the absence or
      presence of the inducer naringenin, nodA transcription was initiated
      constitutively with no requirement for the inducer naringenin or, even, the NodD
      regulating protein.

PMID- 15872219
TI  - Development and evaluation of a multitarget real-time Taqman reverse
      transcription-PCR assay for detection of the severe acute respiratory syndrome
      associated coronavirus and surveillance for an apparently related coronavirus
      found in masked palm civets.
AB  - Severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) is the
      etiological agent of SARS. It is believed that SARS-CoV originates from wild
      animals. We have developed a multitarget real-time Taqman reverse transcription
      PCR (RT-PCR) assay for the quantitative detection of SARS-CoV. The sequences of
      the Taqman probes with a minor groove binder and the corresponding primers were
      based on the sequences of the N gene, open reading frame (ORF) 3, and ORF 8. The
      overall linear range of this assay was from at least 10(1) to 10(6) copies per
      reaction, and the detection limit could reach less than 10 copies per reaction.
      The quantification results for SARS-CoV from cell culture correlated well with
      those of the RT-PCR by using any two of the three sets of primer and probe used
      in this assay. However, the results of quantification of SARS-CoV obtained by
      using a few available throat swab specimens from SARS patients and the N gene as
      the target were almost 10 times higher than those obtained by using ORF 3 and ORF
      8. Using this assay, we also detected an apparently SARS-CoV-related coronavirus
      in the throat swab specimens from masked palm civets in the west part of Hubei
      Province, People's Republic of China.

PMID- 15872218
TI  - Alternative polyadenylation of cyclooxygenase-2.
AB  - A biologically important human gene, cyclooxygenase-2 (COX-2), has been proposed
      to be regulated at many levels. While COX-1 is constitutively expressed in cells,
      COX-2 is inducible and is upregulated in response to many signals. Since
      increased transcriptional activity accounts for only part of the upregulation of
      COX-2, we chose to explore other RNA processing mechanisms in the regulation of
      this gene. We performed a comprehensive bioinformatics survey, the first of its
      kind known for human COX-2, which revealed that the human COX-2 gene has
      alternative polyadenylation (proximal and distal sites) and suggested that use of
      the alternative polyadenylation signals has tissue specificity. We experimentally
      established this in HepG2 and HT29 cells. We used an in vivo polyadenylation
      assay to examine the relative strength of the COX-2 proximal and distal
      polyadenylation signals, and have shown that the proximal polyadenylation signal
      is much weaker than the distal one. The efficiency of utilization of many
      suboptimal mammalian polyadenylation signals is affected by sequence elements
      located upstream of the AAUAAA, known as upstream efficiency elements (USEs).
      Here, we used in vivo polyadenylation assays in multiple cell lines to
      demonstrate that the COX-2 proximal polyadenylation signal contains USEs,
      mutation of the USEs substantially decreased usage of the proximal signal, and
      that USE spacing relative to the polyadenylation signal was significant. In
      addition, mutation of the COX-2 proximal polyadenylation signal to a more optimal
      sequence enhanced polyadenylation efficiency 3.5-fold. Our data suggest for the
      first time that alternative polyadenylation of COX-2 is an important post
      transcriptional regulatory event.

PMID- 15872220
TI  - Consensus sequence-based scheme for epidemiological typing of clinical and
      environmental isolates of Legionella pneumophila.
AB  - A previously described sequence-based epidemiological typing method for clinical
      and environmental isolates of Legionella pneumophila serogroup 1 was extended by
      the investigation of three additional gene targets and modification of one of the
      previous targets. Excellent typeability, reproducibility, and epidemiological
      concordance were determined for isolates belonging to both serogroup 1 and the
      other serogroups investigated. Gene fragments were amplified from genomic DNA,
      and PCR amplicons were sequenced by using forward and reverse primers. Consensus
      sequences are entered into an online database, which allows the assignment of
      individual allele numbers. The resulting sequence-based type or allelic profile
      comprises a string of the individual allele numbers separated by commas, e.g.,
      1,4,3,1,1,1, in a predetermined order, i.e., flaA, pilE, asd, mip, mompS, and
      proA. The index of discrimination (D) obtained with these six loci was calculated
      following analysis of a panel of 79 unrelated clinical isolates. A D value of >
      0.94 was obtained, and this value appears to be sufficient for use in the
      epidemiological investigation of outbreaks caused by L. pneumophila. The D value
      rose to 0.98 when the results of the analysis were combined with those of
      monoclonal antibody subgrouping. Sequence-based typing of L. pneumophila is
      epidemiologically concordant and discriminatory, and the data are easily
      transportable. This consensus method will assist in the epidemiological
      investigation of L. pneumophila infections, especially travel-associated cases,
      by which it will allow a rapid comparison of isolates obtained in more than one
      country.

PMID- 15872221
TI  - Comparison of commercial real-time PCR assays for quantification of Epstein-Barr
      virus DNA.
AB  - Clinical research suggests a role for viral load measurement in predicting and
      monitoring Epstein-Barr virus (EBV)-associated diseases. The aim of this study
      was to assess the performance of the recently commercially available quantitative
      assays for EBV based on real-time PCR: the RealArt EBV LC PCR kit and the
      LightCycler EBV quantification kit. A total of 87 samples were analyzed: 67
      samples were obtained from transplant recipients and patients with EBV-associated
      diseases, 8 samples were obtained from the Quality Control for Molecular
      Diagnostics 2002 EBV Proficiency Program, and 12 negative qualitative nested PCR
      samples were used as negative controls. Inter- and intra-assay variabilities were
      determined by running replicates of two samples. All samples were run in a
      LightCycler instrument. The differences between positive and negative results
      were not considered statistically significant (P = 0.5355). There were no false
      positive results using either method for nested PCR negative-control samples. The
      difference in viral load values using the two different methods was considered
      statistically significant (P < 0.01). The logarithmic linear correlation for both
      assays was low (r = 0.449) but significant (P < 0.01). The LightCycler EBV
      quantification kit showed a wider dispersal in results but produced substantially
      more-accurate melting temperature profile curves. The bias towards lower
      measurements was considerable in comparison with higher viral load. The
      differences in PCR efficiency and the presence of mutations could explain the
      disparity between the two methods. It was concluded that confidence intervals
      would be required to report the results rather than plain absolute values of
      viral load for patient monitoring.

PMID- 15872222
TI  - Detection and typing of Herpes Simplex virus (HSV) in mucocutaneous samples by
      TaqMan PCR targeting a gB segment homologous for HSV types 1 and 2.
AB  - Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) are major causes of
      mucocutaneous lesions and severe infections of the central nervous system. Here a
      new semiautomated method for detecting and typing of HSV was used to analyze 479
      mucocutaneous swab samples. After DNA extraction using a Magnapure LC robot, a
      118-bp segment of the gB region was amplified by real-time PCR utilizing type
      specific TaqMan probes to identify HSV-1 or HSV-2. HSV detection in a single well
      using probes labeled with carboxyfluorescein (FAM) for HSV-1 and JOE (6-carboxy
      4',5'-dichloro-2',7'-dimethoxyfluorescein) for HSV-2 had a sensitivity similar to
      that seen in separate reactions. All but one of 217 samples (99.5%) that had been
      positive by virus culture were positive by TaqMan PCR, with a correct
      identification of type in all cases. Out of 262 samples negative by virus
      culture, 48 (18.3%) were positive by TaqMan PCR, with higher Ct values compared
      with culture positive samples (P < 0.0001). Overall, the Ct values for HSV-1 were
      lower than for HSV-2 (mean, 25.5 versus 27.9), but to some extent this could be
      due to weaker fluorescence by JOE. Lower C(t) values for HSV-1 were seen also in
      the 202 genital samples (79 HSV-1, 122 HSV-2, 1 HSV-1 and HSV-2), indicating that
      HSV-1 replicates as well as HSV-2 in the genital area. HSV-1 constituted 40% of
      genital infections and was associated with lower mean age (29.2 versus 36.4
      years), probably reflecting the fact that recurrent genital HSV-1 infections are
      rare.

PMID- 15872223
TI  - Enhanced enzyme immunoassay with negative-gray-zone testing compared to a single
      nucleic Acid amplification technique for community-based chlamydial screening of
      men.
AB  - We evaluated a low-cost diagnostic strategy for detecting Chlamydia trachomatis
      in a low-prevalence population. We used an amplified enzyme immunoassay (EIA)
      with a reduced-cutoff "negative gray zone" to identify reactive specimens for
      confirmation by a nucleic acid amplification test. As part of the Chlamydia
      Screening Studies project, men provided a first-pass urine specimen, which they
      returned by post for testing. We tested 1,003 specimens by IDEIA PCE EIA (Dako)
      and Cobas PCR (Roche). There were 32 (3.2%) true positive specimens according to
      a combined standard using an algorithm requiring concordant results from at least
      two independent tests. All of these were positive by Cobas PCR and 24 were
      confirmed to be positive by PCE EIA, including 2 that gave results in the
      negative gray zone. There were 971 true negative specimens, 2 of which were
      positive by Cobas PCR and 19 of which were initially inhibitory for PCR. The
      relative sensitivity, specificity, positive predictive value, and negative
      predictive value of PCE EIA with PCR confirmation were 75.0% (95% confidence
      interval [CI], 56.6 to 88.5%), 100% (95% CI, 99.7 to 100%), 100% (95% CI, 88.3 to
      100%), and 99.2% (95% CI, 98.4 to 99.6%), respectively. The corresponding values
      for Cobas PCR were 100% (95% CI, 89.1 to 100%), 99.8% (95% CI, 99.3 to 100%),
      94.1% (95% CI, 76.9 to 98.2%), and 100% (95% CI, 99.6 to 100%), respectively,
      with 1.9% (19/1003) of the samples being initially indeterminate. When the
      prevalence of C. trachomatis is low, the use of an amplified EIA on urine
      specimens, with confirmation of results in the negative gray zone by use of a
      nucleic acid amplification technique, is not suitable for screening asymptomatic
      men. In addition, positive nucleic acid amplification test results should be
      confirmed and an inhibition control should be used.

PMID- 15872224
TI  - ESAT-6/CFP-10 fusion protein and peptides for optimal diagnosis of mycobacterium
      tuberculosis infection by ex vivo enzyme-linked immunospot assay in the Gambia.
AB  - Overlapping peptides of Mycobacterium tuberculosis antigens ESAT-6 and CFP-10
      offer increased specificity over the purified protein derivative skin test when
      they were used in an ex vivo enzyme-linked immunospot (ELISPOT) assay for gamma
      interferon detection for the diagnosis of M. tuberculosis infection from recent
      exposure. We assessed whether equivalent results could be obtained for a fusion
      protein of the two antigens and whether a combined readout would offer increased
      sensitivity in The Gambia. We studied the ELISPOT assay results for 488 household
      contacts of 88 sputum smear-positive tuberculosis (TB) cases. The proportions of
      subjects positive by each test and by the tests combined were assessed across an
      exposure gradient, defined according to sleeping proximity to a TB case. Eighty
      eight (18%) subjects were positive for CFP-10 peptides, 148 (30%) were positive
      for ESAT-6 peptides, 161 (33%) were positive for both peptides, and 168 (34%)
      were positive for the fusion protein; 188 (39%) subjects had either a positive
      result for a peptide or a positive result for the fusion protein. There was
      reasonable agreement between the peptide and the protein results (kappa statistic
      = 0.78) and no significant discordance (P = 0.38). There was a strong correlation
      between the fusion protein and combined peptide spot counts (r = 0.9), and
      responses to the peptide and the proteins all increased significantly according
      to M. tuberculosis exposure. The proportion of subjects positive for either the
      pool of peptides or the fusion protein offered maximum sensitivity, being
      significantly higher than the proportion of subjects positive for ESAT-6 peptides
      alone (P = 0.007). A fusion protein of ESAT-6 and CFP-10 is equivalent to
      overlapping peptides for the diagnosis of latent M. tuberculosis infection. Use
      of a combination of peptides and fusion protein offers improved sensitivity.

PMID- 15872225
TI  - Workload due to Aspergillus fumigatus and significance of the organism in the
      microbiology laboratory of a general hospital.
AB  - The increase in the immunocompromised population and the incidence of invasive
      aspergillosis (IA) are leading to an overinterpretation of the potential clinical
      significance of many isolates of Aspergillus fumigatus. Our work prospectively
      assesses the workload of the isolation of A. fumigatus and its clinical
      significance in the microbiology laboratory of a large teaching hospital. During
      a 3-year period, all patients from whom A. fumigatus was isolated were
      prospectively monitored and classified as having IA or "nonsignificant" disease.
      A point score based on the prediction of five easily obtained laboratory and
      clinical parameters was applied. We found 404 A. fumigatus isolates in 260
      patients (1/1,000 microbiology laboratory samples; 2.1 patients/10,000
      admissions). A total of 90 isolates (22.3%) were from patients with IA. Of the
      260 patients, 31 (12%) had invasive disease (IA), and the remaining 229 had
      "nonsignificant" disease. A score based on points for five parameters was applied
      to our population. It was constructed as follows: "sample obtained by invasive
      procedures" (1 point), "presence of two or more positive samples from the same
      patient" (1 point), "leukemia" (2 points), "neutropenia" (5 points), and
      "corticosteroid treatment" (2 points). Patients with a score of 0 had only a 2.5%
      probability of IA. Those with a score of 1 or 2 had an increased probability of
      10.3%. The probabilities rose to 40% and 70%, respectively, for patients with a
      score of 3 or 4 or a score of > or = 5. A simple score based on five easily
      available parameters may be of help to microbiologists and clinicians to predict
      the risk of IA.

PMID- 15872226
TI  - Use of the oxford multilocus sequence typing protocol and sequencing of the
      flagellin short variable region to characterize isolates from a large outbreak of
      waterborne Campylobacter sp. strains in Walkerton, Ontario, Canada.
AB  - The Walkerton (Ontario, Canada) outbreak of waterborne Escherichia coli O157:H7
      and Campylobacter jejuni was quite limited in both space and time, making it a
      good model for exploring the utility of different typing and subtyping methods
      for the characterization of relationships among isolates of these organisms. We
      have extended previous work with these organisms through analysis by the Oxford
      multilocus sequence typing (MLST) and the flagellin short variable region (fla
      SVR) sequencing methods. Additional isolates not epidemiologically related to the
      Walkerton outbreak have also been included. Both sequencing methods identified
      and differentiated between Walkerton outbreak strains 1 and 2. When these strains
      were compared with isolates that were not part of the outbreak, the information
      produced by the fla-SVR method more often correlated with epidemiological
      findings than that produced by MLST, though both methods were required for
      optimal discrimination. The MLST data were more relevant in terms of the overall
      population structure of the organisms. Both mutation and recombination appeared
      to be responsible for generating diversity among the isolates tested.

PMID- 15872227
TI  - Assessment of ribosomal large-subunit D1-D2, internal transcribed spacer 1, and
      internal transcribed spacer 2 regions as targets for molecular identification of
      medically important Aspergillus species.
AB  - Molecular approaches are now being developed to provide a more rapid and
      objective identification of fungi compared to traditional phenotypic methods.
      Ribosomal targets, especially the large-subunit RNA gene (D1-D2 region) and
      internal transcribed spacers 1 and 2 (ITS1 and ITS2 regions), have shown
      particular promise for the molecular identification of some fungi. We therefore
      conducted an assessment of these regions for the identification of 13 medically
      important Aspergillus species: Aspergillus candidus, Aspergillus (Eurotium)
      chevalieri, Aspergillus (Fennellia) flavipes, Aspergillus flavus, Aspergillus
      fumigatus, Aspergillus granulosus, Aspergillus (Emericella) nidulans, Aspergillus
      niger, Aspergillus restrictus, Aspergillus sydowii, Aspergillus terreus,
      Aspergillus ustus, and Aspergillus versicolor. The length of ribosomal regions
      could not be reliably used to differentiate among all Aspergillus species
      examined. DNA alignment and pairwise nucleotide comparisons demonstrated 91.9 to
      99.6% interspecies sequence identities in the D1-D2 region, 57.4 to 98.1% in the
      ITS1 region, and 75.6 to 98.3% in the ITS2 region. Comparative analysis using
      GenBank reference data showed that 10 of the 13 species examined exhibited a < or
      = 1-nucleotide divergence in the D1-D2 region from closely related but different
      species. In contrast, only 5 of the species examined exhibited a < or = 1
      nucleotide divergence from sibling species in their ITS1 or ITS2 sequences.
      Although the GenBank database currently lacks ITS sequence entries for some
      species, and major improvement in the quality and accuracy of GenBank entries is
      needed, current identification of medically important Aspergillus species using
      GenBank reference data seems more reliable using ITS query sequences than D1-D2
      sequences, especially for the identification of closely related species.

PMID- 15872228
TI  - Genotypic study of Pneumocystis jirovecii in human immunodeficiency virus
      positive patients in Thailand.
AB  - Pneumocystis jirovecii is one of the common opportunistic infections in human
      immunodeficiency virus (HIV)-infected patients in Thailand. Information regarding
      genotypic and epidemiological of this organism in Thai patients is not available.
      We analyzed the genotypes of 28 P. jirovecii-positive specimens from
      bronchoalveolar lavage and sputum samples from HIV-infected Thai patients based
      on nucleotide variations of the internal transcribed spacer regions 1 and 2 of
      the rRNA gene. Thirteen genotypes were the same as previously reported outside
      Thailand. Ten genotypes, which included Bp, Er, Eq, Ic, Ir, Ip, Rc, Rp, Qb, and
      Qq, were new. Ir and Rp were unique and dominant types observed in HIV-infected
      Thai patients. Thirteen specimens (46.4%) were infected with a single type of P.
      jirovecii, and fifteen (53.6%) were mixed infections. These differences may be
      used as genotypic markers for studying the epidemiology and transmission of P.
      jirovecii in the Thai population.

PMID- 15872229
TI  - Rapid detection and typing of strains of Mycobacterium avium subsp.
      paratuberculosis from broth cultures.
AB  - A liquid culture followed by molecular confirmation was evaluated for potential
      to improve sensitivity and reduce time to diagnosis of Mycobacterium avium subsp.
      paratuberculosis infection. Fecal samples from 240 animals from Ohio farms were
      assessed for presence of M. avium subsp. paratuberculosis using four different
      protocols: (i) sedimentation processing followed by inoculation on Herrold's Egg
      Yolk media (HEYM) slants (monitored biweekly up to 16 weeks), (ii) double
      centrifugation processing followed by inoculation on HEYM slants (monitored
      biweekly up to 16 weeks), (iii) liquid-solid double culture method using modified
      7H9 broth (8 weeks) followed by subculture on HEYM slants (monitored up to 8
      weeks), and (iv) liquid culture using modified 7H9 broth (8 weeks) followed by
      molecular assays for the presence of two M. avium subsp. paratuberculosis
      specific targets. The number of positive samples detected by each protocol was
      37, 53, 65, and 76, respectively. Twenty-seven samples were positive by all four
      methods. Based on samples positive by at least one method (n = 81), the
      sensitivities for sedimentation processing, double centrifugation processing,
      liquid-solid double culture, and liquid culture followed by molecular
      confirmation were 46%, 65%, 80%, and 94%, respectively. Fingerprinting of the
      positive samples using two polymorphic (G and GGT) short sequence repeat regions
      identified varying levels of within-farm and between-farm diversity. Our data
      indicate that liquid culture followed by molecular confirmation can significantly
      improve sensitivity and reduce time-to-diagnosis (from 16 to 8 weeks) of M. avium
      subsp. paratuberculosis infection and can also be efficiently employed for the
      systematic differentiation of M. avium subsp. paratuberculosis strains to
      understand the epidemiology of Johne's disease.

PMID- 15872230
TI  - Dissemination of community-acquired methicillin-resistant Staphylococcus aureus
      clones in northern Norway: sequence types 8 and 80 predominate.
AB  - Increasing frequencies of community-acquired methicillin-resistant Staphylococcus
      aureus (MRSA) strain isolation have been reported from many countries. The
      overall prevalence of MRSA in Norway is still very low. MRSA isolates (n = 67)
      detected between 1995 and 2003 in northern Norway were analyzed by pulsed-field
      gel electrophoresis, multilocus sequence typing, and staphylococcal cassette
      chromosome mec (SCCmec) typing. Sixty-seven isolates were associated with 13
      different sequence types. Two successful MRSA clones predominated. Sequence type
      8 (ST8) (40%) and ST80 (19%) containing SCCmec type IV were detected in hospitals
      and communities in different geographic regions during a 7-year period. In
      general, there was a low level of antimicrobial resistance. Only 26% of the
      isolates were multiresistant. International epidemic clones were detected. The
      frequent findings of SCCmec type IV (91%) along with heterogeneous genetic
      backgrounds suggest a horizontal spread of SCCmec type IV among staphylococcal
      strains in parallel with the clonal spread of successful MRSA strains.

PMID- 15872231
TI  - Molecular epidemiology of macrolide-resistant isolates of Streptococcus
      pneumoniae collected from blood and respiratory specimens in Norway.
AB  - Norway has a low prevalence of antimicrobial resistance, including macrolide
      resistant Streptococcus pneumoniae (MRSP). In a nationwide surveillance program,
      a total of 2,200 S. pneumoniae isolates were collected from blood cultures and
      respiratory tract specimens. Macrolide resistance was detected in 2.7%. M-type
      macrolide resistance was found in 60% of resistant isolates, and these were
      mainly mef(A)-positive, serotype-14 invasive isolates. The erm(B)-encoded
      macrolide-lincosamide-streptogramin B (MLS(B)) type dominated among the
      noninvasive isolates. One strain had an A2058G mutation in the 23S rRNA gene.
      Coresistance to other antibiotics was seen in 96% of the MLS(B)-type isolates,
      whereas 92% of the M-type isolates were susceptible to other commonly used
      antimicrobial agents. Serotypes 14, 6B, and 19F accounted for 84% of the
      macrolide-resistant isolates, with serotype 14 alone accounting for 67% of the
      invasive isolates. A total of 29 different sequence types (STs) were detected by
      multilocus sequence typing. Twelve STs were previously reported international
      resistant clones, and 75% of the macrolide-resistant isolates had STs identical
      or closely related to these clones. Eleven isolates displayed 10 novel STs, and
      7/11 of these "Norwegian strains" coexpressed MLS(B) and tetracycline resistance,
      indicating the presence of Tn1545. The invasive serotype-14 isolates were all
      classified as ST9 or single-locus variants of this clone. ST9 is a mef-positive M
      type clone, commonly known as England(14)-9, reported from several European
      countries. These observations suggest that the import of major international MRSP
      clones and the local spread of Tn1545 are the major mechanisms involved in the
      evolution and dissemination of MRSP in Norway.

PMID- 15872232
TI  - Evaluation of the COBAS Hepatitis C Virus (HCV) TaqMan analyte-specific reagent
      assay and comparison to the COBAS Amplicor HCV Monitor V2.0 and Versant HCV bDNA
      3.0 assays.
AB  - Performance characteristics of the COBAS hepatitis C virus (HCV) TaqMan analyte
      specific reagent (TM-ASR) assay using the QIAGEN BioRobot 9604 for RNA extraction
      were evaluated and compared to the COBAS Amplicor HCV Monitor V2.0 (Amplicor) and
      Versant HCV bDNA 3.0 (Versant) assays using clinical samples. Calibration of TM
      ASR using Armored RNA allowed determination of the distribution of HCV RNA in
      clinical samples, using 22,399 clinical samples. Limit of detection, linearity,
      and inter- and intraassay assay precision were determined for the TM-ASR assay
      using multiple clinical specimen panels across multiple determinations. Genotype
      specificity for the TM-ASR assay was determined using samples with different HCV
      RNA genotypes evaluated and compared against predetermined results. Contamination
      control of the TM-ASR assay was evaluated using pools of HCV RNA-positive and 
      negative samples tested in a checkerboard pattern over 12 runs of 96 samples.
      Correlation of the TM-ASR, Amplicor, and Versant assays was determined using 100
      paired clinical samples and Deming regression analysis. The TM-ASR performed well
      with respect to linearity, precision, and contamination control. The correlation
      between TM-ASR and the Amplicor and Versant assays was poor, with large
      differences between assay results for individual samples. Calibration of the TM
      ASR assay with Armored RNA allowed for a wide dynamic range and description of
      the distribution of HCV RNA in clinical samples.

PMID- 15872233
TI  - Repetitive-sequence-PCR-based DNA fingerprinting using the Diversilab system for
      identification of commonly encountered dermatophytes.
AB  - The performance of repetitive-sequence-based PCR (rep-PCR) using the DiversiLab
      system for identification of dermatophytes commonly isolated in a clinical
      laboratory was assessed by comparing results to those of conventional tests
      (colony morphology, microscopic examination of slide cultures, and, for suspected
      Trichophyton species, use of additional media). Sixty-one cultures were tested in
      phase 1, the feasibility portion of the study; 64 additional cultures were tested
      in phase 2, the validation portion conducted to assess reproducibility and
      confirm accuracy. Discrepancies were resolved by repeating rep-PCR and
      conventional tests and, in phase 2, sequencing the internal transcribed spacers.
      After initial testing of the cultures in phase 1 (excluding one contaminated
      culture), agreement between conventional tests and rep-PCR was 90% (54 of 60).
      Agreement was 98.3% after resolution of discrepancies, and in all but one case
      the initial rep-PCR result was correct. After initial testing of cultures in
      phase 2 (excluding one discarded and one contaminated culture), agreement between
      rep-PCR and conventional testing was 88.7% (55 of 62). After discrepancies were
      resolved, agreement was 100%. Initial rep-PCR results were correct, except for
      one Microsporum canis culture containing two colony variants, which could not be
      initially identified by rep-PCR. The performance of the DiversiLab system for
      identification of the dermatophytes commonly encountered in a clinical mycology
      laboratory-Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton
      tonsurans, and M. canis-was excellent. Moreover, the DiversiLab system is
      technically simple and provides results in < 24 h once a pure culture is
      available for testing, which is considerably more rapid than conventional
      identification tests.

PMID- 15872234
TI  - Targeted hybridization of IS6110 fingerprints identifies the W-Beijing
      Mycobacterium tuberculosis strains among clinical isolates.
AB  - Targeted IS6110-based RFLP genotyping can be applied to rapidly identify specific
      groups of biomedically/epidemiologically relevant Mycobacterium tuberculosis
      clinical isolates. One such group is the W-Beijing strain family (also known as
      Beijing/W), implicated in significant nosocomial and community outbreaks
      worldwide. Using previously defined criteria, we developed a simple and accurate
      method to identify members of the W-Beijing family, based on rehybridization of
      Southern blot membranes used previously in routine IS6110 DNA fingerprint
      analysis. The hybridization probe constructed ("W-Beijing polyprobe") contains
      the PCR-amplified fragments specific for three M. tuberculosis chromosomal loci
      used for the identification of W-Beijing strains. The targets include the dnaA
      dnaN and NTF regions and the direct repeat locus. A total of 526 selected
      clinical isolates (representative of 253 different IS6110-defined strain types)
      were analyzed using the W-Beijing polyprobe. A total of 148 isolates from this
      collection were found to be members of the W-Beijing phylogenetic lineage,
      comprising 106 strains from the W-Beijing family (46 clusters) and 42 related
      isolates. Rehybridization results were confirmed by computer-assisted analysis.
      The sensitivity and specificity of this method were estimated at 98.7% and 99.7%,
      respectively. This study demonstrates that the W-Beijing polyprobe can accurately
      and reliably discriminate members of the W-Beijing phylogenetic lineage and the W
      Beijing family of M. tuberculosis strains.

PMID- 15872235
TI  - Antifungal susceptibilities of Candida species causing vulvovaginitis and
      epidemiology of recurrent cases.
AB  - There are limited data regarding the antifungal susceptibility of yeast causing
      vulvovaginal candidiasis, since cultures are rarely performed. Susceptibility
      testing was performed on vaginal yeast isolates collected from January 1998 to
      March 2001 from 429 patients with suspected vulvovaginal candidiasis. The charts
      of 84 patients with multiple positive cultures were reviewed. The 593 yeast
      isolates were Candida albicans (n = 420), Candida glabrata (n = 112), Candida
      parapsilosis (n = 30), Candida krusei (n = 12), Saccharomyces cerevisiae ( n =
      9), Candida tropicalis (n = 8), Candida lusitaniae (n = 1), and Trichosporon sp.
      (n = 1). Multiple species suggesting mixed infection were isolated from 27
      cultures. Resistance to fluconazole and flucytosine was observed infrequently
      (3.7% and 3.0%); 16.2% of isolates were resistant to itraconazole (MIC > or = 1
      microg/ml). The four imidazoles (econazole, clotrimazole, miconazole, and
      ketoconazole) were active: 94.3 to 98.5% were susceptible at < or =1 microg/ml.
      Among different species, elevated fluconazole MICs (> or = 16 microg/ml) were
      only observed in C. glabrata (15.2% resistant [R], 51.8% susceptible-dose
      dependent [S-DD]), C. parapsilosis (3.3% S-DD), S. cerevisiae (11.1% S-DD), and
      C. krusei (50% S-DD, 41.7% R, considered intrinsically fluconazole resistant).
      Resistance to itraconazole was observed among C. glabrata (74.1%), C. krusei
      (58.3%), S. cerevisiae (55.6%), and C. parapsilosis (3.4%). Among 84 patients
      with recurrent episodes, non-albicans species were more common (42% versus 20%).
      A > or = 4-fold rise in fluconazole MIC was observed in only one patient with C.
      parapsilosis. These results support the use of azoles for empirical therapy of
      uncomplicated candidal vulvovaginitis. Recurrent episodes are more often caused
      by non-albicans species, for which azole agents are less likely to be effective.

PMID- 15872236
TI  - Global trends in the antifungal susceptibility of Cryptococcus neoformans (1990
      to 2004).
AB  - The antifungal susceptibilities of 1,811 clinical isolates of Cryptococcus
      neoformans obtained from 100 laboratories in 5 geographic regions worldwide
      between 1990 and 2004 were determined. The MICs of amphotericin B, flucytosine,
      fluconazole, voriconazole, posaconazole, and ravuconazole were determined by the
      National Committee for Clinical Laboratory Standards broth microdilution method.
      Isolates were submitted to a central reference laboratory (University of Iowa)
      from study centers in Africa (5 centers, 395 isolates), Europe (14 centers, 102
      isolates), Latin America (14 centers, 82 isolates), the Pacific region (7
      centers, 50 isolates), and North America (60 centers, 1,182 isolates). Resistance
      to amphotericin B, flucytosine, and fluconazole was < or = 1% overall.
      Susceptibility to flucytosine (MIC, < or = 4 microg/ml) ranged from 35% in North
      America to 68% in Latin America. Similarly, only 75% of isolates from North
      America were susceptible to fluconazole (MIC, < or = 8 microg/ml) compared to 94
      to 100% in the other regions. Isolates remained highly susceptible to
      amphotericin B (99% susceptibility at a MIC of < or = 1 microg/ml) over the
      entire 15-year period. Susceptibility to flucytosine (MIC, < or = 4 microg/ml)
      increased from 34% in 1990 to 1994 to 66% in 2000 to 2004. Susceptibility to
      fluconazole (MIC, < or = 8 microg/ml) increased from 72% in 1990 to 1994 to 96%
      in 2000 to 2004. Voriconazole, posaconazole, and ravuconazole all were very
      active (99% of isolates susceptible at MIC of < or = 1 microg/ml) against this
      geographically diverse collection of isolates. We conclude that in vitro
      resistance to antifungal agents used in the treatment of cryptococcosis remains
      uncommon among isolates of C. neoformans from five broad geographic regions and
      has not increased over a 15-year period.

PMID- 15872237
TI  - Real-time-PCR assay for diagnosis of Entamoeba histolytica infection.
AB  - We developed a real-time-PCR assay utilizing a molecular-beacon probe for the
      detection of Entamoeba histolytica and compared its sensitivity to stool antigen
      detection and traditional PCR. A total of 205 stool and liver abscess pus
      specimens from patients and controls were used for this purpose, 101 (49%) of
      which were positive by the TechLab E. histolytica-specific antigen detection
      test, while the other 104 (51%) stool and liver abscess pus specimens were
      negative by the antigen detection test. DNA was extracted from the stool and
      liver abscess pus specimens by the QIAGEN method and the small-subunit rRNA gene
      of E. histolytica and then amplified by traditional and real-time PCR. Out of
      these 205 stool and liver abscess pus specimens, 124 were positive by the real
      time-PCR assay and 90 were positive by the traditional-PCR test. Compared to the
      real-time-PCR assay, the antigen detection test was 79% sensitive and 96%
      specific. When the traditional-PCR test results were compared to the real-time
      PCR assay, the sensitivity of traditional PCR was 72% and the specificity was
      99%. In conclusion, all three methods for the detection of E. histolytica were
      highly specific, with real-time PCR being the most sensitive.

PMID- 15872239
TI  - Comparison of non-culture-based methods for detection of systemic fungal
      infections, with an emphasis on invasive Candida infections.
AB  - The accepted limitations associated with classic culture techniques for the
      diagnosis of invasive fungal infections have lead to the emergence of many non
      culture-based methods. With superior sensitivities and quicker turnaround times,
      non-culture-based methods may aid the diagnosis of invasive fungal infections. In
      this review of the diagnostic service, we assessed the performances of two
      antigen detection techniques (enzyme-linked immunosorbent assay [ELISA] and latex
      agglutination) with a molecular method for the detection of invasive Candida
      infection and invasive aspergillosis. The specificities for all three assays were
      high (> or = 97%), although the Candida PCR method had enhanced sensitivity over
      both ELISA and latex agglutination with values of 95%, 75%, and 25%,
      respectively. However, calculating significant sensitivity values for the
      Aspergillus detection methods was not feasible due to a low number of
      proven/probable cases. Despite enhanced sensitivity, the PCR method failed to
      detect nucleic acid in a probable case of invasive Candida infection that was
      detected by ELISA. In conclusion, both PCR and ELISA techniques should be used in
      unison to aid the detection of invasive fungal infections.

PMID- 15872240
TI  - Clinical impact associated with corrected results in clinical microbiology
      testing.
AB  - We developed a strategy to determine the clinical impact associated with errors
      in clinical microbiology testing. Over a 9-month period, we used a sequential
      three-stage method to prospectively evaluate 480 consecutive corrected
      microbiology laboratory reports. The three stages were physician review of the
      corrected report, medical record review, and interview with the clinician(s)
      taking care of the patient. Of the 480 corrected reports, 301 (62.7%) were ruled
      out for significant clinical impact by physician review and an additional 25
      cases (5.2%) were ruled out for clinical impact by medical record review. This
      left 154 cases (32.1%) that required clinician interview to determine clinical
      impact. The clinician interview revealed that 32 (6.7%) of the corrected reports
      were associated with adverse clinical impact. Of these 32 cases, 19 (59.4%)
      involved delayed therapy, 8 (25.0%) involved unnecessary therapy, 8 (25.0%) were
      associated with inappropriate therapy, and 4 (12.5%) were associated with an
      increased level of care. The laboratory was entirely responsible for the error in
      28 (87.5%) of the 32 cases and partially responsible in the other 4 cases
      (12.5%). Twenty-six (81.3%) of the 32 cases involved potentially preventable
      analytic errors that were due to lack of knowledge (cognitive error). In summary,
      we used evaluation of corrected reports to identify laboratory errors with
      adverse clinical impact, and most of the errors were amenable to laboratory-based
      interventions. Our method has the potential to be implemented in other laboratory
      settings to identify and characterize errors that impact patient safety.

PMID- 15872238
TI  - Effect of prophylactic valacyclovir on the presence of human herpesvirus DNA in
      saliva of healthy individuals after dental treatment.
AB  - Human herpesviruses (HHVs) are ubiquitous pathogens that intermittently
      reactivate from latency. Transmission is believed to be facilitated by their
      frequent appearance in saliva. This study sought to understand the factors that
      influence the appearance of these viruses in saliva by examining the prevalence,
      pattern, and quantity of all eight HHVs in saliva of immunocompetent adults with
      a history of recurrent oral herpes simplex virus (HSV) infections following
      dental treatment and antiviral therapy. Valacyclovir or matched placebo was given
      (2 g twice on the day of treatment and 1 g twice the following day) to 125
      patients in a randomized, double-blind controlled trial. Saliva, collected on the
      day of dental treatment and 3 and 7 days later, was analyzed using real-time
      quantitative PCR. At all visits, HHVs coinfected saliva. Over the course of the
      week, the DNAs of HHV-6 and HHV-7 were detected significantly more often (97% to
      99% of patients) than Epstein-Barr virus (EBV; 64.8%), HSV-1 (13.0%), HHV-8
      (3.2%), cytomegalovirus (2.4%), HSV-2 (0%), and varicella-zoster virus (0%),
      irrespective of drug treatment (P < 0.002). Mean genome copy numbers were highest
      for HSV-1 and HHV-6. Dental treatment did not influence asymptomatic viral
      shedding patterns. However, valacyclovir treatment resulted in significantly
      fewer patients shedding EBV at both postoperative visits compared with placebo (P
      < 0.008). These results suggest that HHVs are simultaneously present in the
      saliva of healthy adults at levels that could facilitate transmission, and
      valacyclovir therapy decreases the prevalence of EBV in saliva but has little
      effect on HHV-6 and HHV-7.

PMID- 15872241
TI  - Comparison of Borrelia burgdorferi sensu lato strains isolated from specimens
      obtained simultaneously from two different sites of infection in individual
      patients.
AB  - The aim of the present study was to analyze and compare Borrelia strains isolated
      from two different specimens obtained simultaneously from individual patients
      with Lyme borreliosis. Fifty such patients and 50 corresponding pairs of Borrelia
      isolates (100 low-propagated strains) were subjected to genotypic and phenotypic
      analysis, including pulsed-field gel electrophoresis for species identification
      and plasmid profile determination and protein profile electrophoresis for the
      assessment of the presence and molecular masses of separated proteins. The
      strains were isolated from two distinct skin lesions (12 patients), skin and
      blood (28 patients), skin and cerebrospinal fluid (8 patients), and blood and
      cerebrospinal fluid (2 patients). Out of 100 isolates, 63 were typed as B.
      afzelii and 37 as B. garinii. From each individual specimen only a single
      Borrelia species was cultured. Comparison of 50 Borrelia strain pairs isolated
      from two different specimens of an individual patient revealed that 12/50 (24%)
      patients were simultaneously infected with two different Borrelia strains; in
      3/50 (6%) patients strains differed at the species level, in 4 out of the
      remaining 47 (9%) patients a strain difference in plasmid profile was
      established, while 5 out of the remaining 43 (11%) patient strain pairs differed
      in regard to the protein profiles of the two concurrently isolated strains. The
      results of the present study indicate that human patients with Lyme borreliosis
      may simultaneously harbor different B. burgdorferi sensu lato strains.

PMID- 15872242
TI  - Comparison of diagnostic laboratory methods for identification of Burkholderia
      pseudomallei.
AB  - Limited experience and a lack of validated diagnostic reagents make Burkholderia
      pseudomallei, the cause of melioidosis, difficult to recognize in the diagnostic
      microbiology laboratory. We compared three methods of confirming the identity of
      presumptive B. pseudomallei strains using a collection of Burkholderia species
      drawn from diverse geographic, clinical, and environmental sources. The 95
      isolates studied included 71 B. pseudomallei and 3 B. thailandensis isolates. The
      API 20NE method identified only 37% of the B. pseudomallei isolates. The
      agglutinating antibody test identified 82% at first the attempt and 90% including
      results of a repeat test with previously negative isolates. Gas-liquid
      chromatography analysis of bacterial fatty acid methyl esters (GLC-FAME)
      identified 98% of the B. pseudomallei isolates. The agglutination test produced
      four false positive results, one B. cepacia, one B. multivorans, and two B.
      thailandensis. API produced three false positive results, one positive B. cepacia
      and two positive B. thailandensis. GLC-FAME analysis was positive for one B.
      cepacia isolate. On the basis of these results, the most robust B. pseudomallei
      discovery pathway combines the previously recommended isolate screening tests
      (Gram stain, oxidase test, gentamicin and polymyxin susceptibility) with
      monoclonal antibody agglutination on primary culture, followed by a repeat after
      24 h incubation on agglutination-negative isolates and GLC-FAME analysis.
      Incorporation of PCR-based identification within this schema may improve
      percentages of recognition further but requires more detailed evaluation.

PMID- 15872243
TI  - Population structure, antimicrobial resistance, and mutation frequencies of
      Streptococcus pneumoniae isolates from cystic fibrosis patients.
AB  - Forty-eight Streptococcus pneumoniae isolates recovered from sputum samples from
      26 cystic fibrosis (CF) patients attending our CF unit (1995 to 2003) were
      studied. Mean yearly incidence of isolation was 5.5%, and all were strains
      recovered from young patients (< or = 12 years). The isolation was linked to
      clinical exacerbation in 35% of the cases, but only 27% of these were not
      accompanied by other CF pathogens. Fifty percent of the patients presented with
      two to four isolates over the studied period. Pulsed-field gel electrophoresis
      SmaI digestion revealed a high heterogeneity (32 pulsotypes among 48 isolates)
      and the persistence over a 6-month period of a single clone (clone A) in two
      patients. This clone, presenting a varied multiresistance phenotype, was
      identified as the Spain23F-1 clone and was also recognized in six other patients,
      including two out of nine patients from the CF unit of Sant Joan de Deu Hospital,
      Barcelona, Spain. In our isolates, 16 different serotypes were recognized, the
      most frequent being 23F (33.3%), 19F (18.8%), 6A (6.2%), and 6B (6.2%). High
      overall resistance rates were observed: to penicillin, 73%; to cefotaxime, 33%;
      to erythromycin, 42%; to tetracycline, 58%; to chloramphenicol, 48%; and to
      trimethoprim-sulfamethoxazole, 67%. Resistance to fluoroquinolones was not
      detected. Multiresistance was a common feature (60%). The percentage of S.
      pneumoniae strains with increased frequencies of mutation to rifampin resistance
      (> or = 7.5 x 10(-8)) was significantly higher (P = 0.02) in CF (60%) than among
      non-CF (37%) isolates in the same institution (M. I. Morosini et al., Antimicrob.
      Agents Chemother. 47:1464-1467, 2003). Even though a clear association with acute
      exacerbations could not be observed, long-term clonal persistence and
      variability, high frequency of antibiotic resistance, and hypermutability
      indicate the plasticity for adaptation of S. pneumoniae to the CF lung
      environment.

PMID- 15872244
TI  - Multilocus sequence typing lacks the discriminatory ability of pulsed-field gel
      electrophoresis for typing Salmonella enterica serovar Typhimurium.
AB  - Nontyphoidal salmonellae are among the leading causes of food-borne disease in
      the United States. Because of the importance of Salmonella enterica in food-borne
      disease, numerous typing methodologies have been developed. Among the several
      molecular typing methods, pulsed-field gel electrophoresis (PFGE) is currently
      considered the "gold standard" technique in typing Salmonella. The aim of this
      study was to compare the discriminatory power of PFGE to multilocus sequence
      typing (MLST) in typing Salmonella enterica serovar Typhimurium clinical
      isolates. A total of 85 Salmonella Typhimurium clinical isolates from cattle were
      used in this study. PFGE using XbaI was performed on the 85 isolates by the
      Centers for Disease Control and Prevention method, and data were analyzed using
      the BioNumerics software package. Fifty PFGE profiles were observed among the
      isolates, and these grouped into three major clusters. For the MLST analysis, the
      manB, pduF, glnA, and spaM genes were amplified by PCR from the same 85 isolates.
      DNA sequencing of these four genes, manB, pduF, glnA, and spaM, showed no genetic
      diversity among the isolates tested, with a 100% identity in nucleotide sequence.
      Moreover, the DNA sequences of the aforementioned genes showed 100% identity to
      the sequence reported in GenBank for the S. enterica serovar Typhimurium LT2
      strain. Therefore, MLST, using these genes, lacks the discriminatory power of
      PFGE for typing Salmonella enterica serovar Typhimurium.

PMID- 15872245
TI  - Significance of transiently positive enzyme-linked immunosorbent assay results in
      detection of Helicobacter pylori in stool samples from children.
AB  - In young children, the significance of stool samples transiently positive for
      Helicobacter pylori antigen is unknown. As part of a larger prospective study on
      enteric infections, stool samples were obtained from 323 children at two time
      points 3 months apart and tested for H. pylori antigen using a commercially
      available enzyme-linked immunosorbent assay (ELISA) test. Seminested PCR for a
      Helicobacter-specific 16S rRNA gene was performed on all 26 pairs reverting from
      positive to negative (transient positives), all 4 persistent antigen-positive
      pairs, and 10 randomly selected persistent antigen-negative pairs. Helicobacter
      species were amplified from the first stool samples of 15/26 (58%) of the
      transient positives and 1 (25%) of 4 persistent positives. No Helicobacter
      species were amplified from the 10 persistent negatives. Among the 15 amplicons
      from transient-positive stool, H. pylori was sequenced and identified from 12
      (80%; 95% confidence interval, 52% to 96%) and other Helicobacter spp. were
      identified from three (Helicobacter canis, Helicobacter winghamensis, and MIT 99
      5504). Four of the 15 remained positive by PCR for the second (antigen-negative)
      stool sample, including all 3 initially identified as non-H. pylori. Helicobacter
      bilis was amplified from the second sample of a persistent positive. Two of eight
      transient positives from whom serum was available had accompanying transient
      elevations in anti-H. pylori antibodies. Transiently positive stool ELISAs for H.
      pylori are common and represent H. pylori in the majority of cases where
      sequences can be obtained. A not-insignificant percentage of antigen-positive
      stools, however, may represent other Helicobacter species.

PMID- 15872246
TI  - Phylogeny and identification of Enterococci by atpA gene sequence analysis.
AB  - The relatedness among 91 Enterococcus strains representing all validly described
      species was investigated by comparing a 1,102-bp fragment of atpA, the gene
      encoding the alpha subunit of ATP synthase. The relationships observed were in
      agreement with the phylogeny inferred from 16S rRNA gene sequence analysis.
      However, atpA gene sequences were much more discriminatory than 16S rRNA for
      species differentiation. All species were differentiated on the basis of atpA
      sequences with, at a maximum, 92% similarity. Six members of the Enterococcus
      faecium species group (E. faecium, E. hirae, E. durans, E. villorum, E. mundtii,
      and E. ratti) showed > 99% 16S rRNA gene sequence similarity, but the highest
      value of atpA gene sequence similarity was only 89.9%. The intraspecies atpA
      sequence similarities for all species except E. faecium strains varied from 98.6
      to 100%; the E. faecium strains had a lower atpA sequence similarity of 96.3%.
      Our data clearly show that atpA provides an alternative tool for the phylogenetic
      study and identification of enterococci.

PMID- 15872247
TI  - Evaluation of conventional and real-time PCR assays using two targets for
      confirmation of results of the COBAS AMPLICOR Chlamydia trachomatis/Neisseria
      gonorrhoeae test for detection of Neisseria gonorrhoeae in clinical samples.
AB  - Two conventional PCR-enzyme immunoassays (PCR-EIAs) and two real-time PCR assays
      (LightCycler system; Roche Diagnostics) were evaluated as confirmation assays
      with cppB and 16S rRNA genes as targets. Of 765 male and female genitourinary and
      nasopharyngeal specimens positive for Neisseria gonorrhoeae in the COBAS AMPLICOR
      Chlamydia trachomatis/Neisseria gonorrhoeae PCR test (Roche Diagnostics), 229
      (30%) were confirmed positive; 13 of these (5.7%) were lacking the cppB gene. Of
      the 534 samples (70%) that could not be confirmed, 81 (15%) showed a positive
      crossing point. However, melting curve analysis revealed an aberrant melting
      temperature in the LightCycler 16S rRNA assay; therefore, these samples were
      considered non-N. gonorrhoeae Neisseria species. Both of the 16S rRNA assays
      performed well, with positive predictive values of 99.1% and 100% for the PCR
      EIAs and the real-time assays, respectively, and a negative predictive value of
      99.8% for both. The cppB assays were compromised by the absence of the cppB gene
      in 5.7% of the N. gonorrhoeae-positive samples, resulting in negative predictive
      values of 96.8% and 97.6% for the PCR-EIAs and the real-time assays,
      respectively. Therefore, the 16S rRNA gene is preferable to the cppB gene as a
      target for confirmation assays. The melting curve analysis of the real-time
      assays provides useful additional information.

PMID- 15872248
TI  - Genotypic analysis of the earliest known prehistoric case of tuberculosis in
      Britain.
AB  - The earliest known case of human tuberculosis in Britain dates to the middle
      period of the Iron Age, approximately 2,200 years before present. Bone lesions on
      the spine of a male skeleton excavated at Tarrant Hinton in Dorset, United
      Kingdom, show evidence of Pott's disease and are supported by molecular evidence
      of Mycobacterium tuberculosis complex DNA amplified by IS6110 PCR (19). In the
      present study, we used a further series of sensitive PCR methods to confirm the
      diagnosis of tuberculosis and to determine the genotype of the infecting strain.
      These tests demonstrated that this individual was infected with a strain of M.
      tuberculosis rather than Mycobacterium bovis. The strain had undergone the
      tuberculosis D1 deletion affecting the mmpS6 and mmpL6 genes and can therefore be
      identified as a member of the family of "modern" M. tuberculosis isolates. All
      evidence obtained was consistent with surviving mycobacterial DNA being highly
      fragmented in this case.

PMID- 15872249
TI  - Investigation of a nosocomial outbreak of imipenem-resistant Acinetobacter
      baumannii producing the OXA-23 beta-lactamase in korea.
AB  - We investigated an outbreak of Acinetobacter baumannii in an intensive care unit
      and in the surgery, medicine, neurology, and urology wards of the Kosin
      University Gospel Hospital in Busan, Korea. The outbreak involved 36 cases of
      infection by A. baumannii producing the OXA-23 beta-lactamase over an 8-month
      period and was caused by a single pulsed-field gel electrophoresis clone. The
      epidemic isolates were characterized by a modified cloverleaf synergy test.
      Isoelectric focusing of crude bacterial extracts detected one nitrocefin-positive
      band with a pI value of 6.65. PCR amplification and characterization of the
      amplicons by direct sequencing indicated that the epidemic isolates carried a
      bla(OXA-23) determinant. The epidemic isolates were characterized by a multidrug
      resistance phenotype that remained unchanged over the outbreak, including
      penicillins, cephamycins, extended-spectrum cephalosporins, carbapenems,
      monobactams, and aminoglycosides. This study shows that the bla(OXA-23)
      resistance determinant may become an emerging therapeutic problem.

PMID- 15872250
TI  - Five-year follow-up study of mother-to-child transmission of Helicobacter pylori
      infection detected by a random amplified polymorphic DNA fingerprinting method.
AB  - Recent studies have speculated on the possible role of the mother in transmitting
      Helicobacter pylori infection to their children. In an attempt to either prove or
      disprove this supposition, we investigated the rates of infection of children
      born to H. pylori-positive mothers from birth to 5 years of age using serology
      and the stool antigen test. When infection of the children did occur, the strains
      from the children were compared to those of their mothers using DNA analysis.
      Sixty-nine of the 350 pregnant mothers (19.7%) had a positive serology for H.
      pylori. Fifty-one children underwent serological examinations and stool antigen
      tests at 4 to 6 days after birth, followed by 1, 3, and 6 months. They were
      continuously given the stool antigen test at 4- to 6-month intervals until the
      age of 5 years. Gastric juice samples were collected from the infected children
      and their mothers for culture and DNA analyses using a random amplified
      polymorphic DNA fingerprinting method. None of the 51 children acquired H. pylori
      infection during the first year of life. Of the 44 children enrolled in a 5-year
      follow-up study, five (11%) acquired H. pylori infection. They acquired the
      infection at the age of 1 year 2 months, 1 year 3 months, 1 year 6 months, 1 year
      8 months, and 4 years 4 months. Random amplified polymorphic DNA fingerprinting
      confirmed that the strains of the five children exhibited DNA fingerprinting
      patterns identical to those of their mothers. These findings suggest that mother
      to-child transmission is the most probable cause of intrafamilial spread of H.
      pylori.

PMID- 15872251
TI  - Detection of bacteria in red blood cell concentrates by the Scansystem method.
AB  - Bacterial contamination remains one of the major risks associated with blood
      product transfusion. The kinetics of bacterial growth in red blood cell
      concentrates (RBCC) is different than otherwise due to storage at 4 degrees C,
      conditions in which most bacteria do not survive. Psychrophilic bacteria such as
      Yersinia enterocolitica, however, can proliferate from a very low level of
      contamination to clinically significant levels at 4 degrees C and are known to
      cause severe transfusion-related infections. A screening method allowing the
      early detection of very low levels of bacteria in RBCC would improve transfusion
      safety. The Scansystem method has been previously described for detection of
      bacteria in platelet concentrates. We present here a modification of the system
      for detection of low levels of bacteria in RBCC. The Scansystem RBC kit protocol
      requires three steps, i.e., the agglutination and selective removal of RBCs, a
      labeling stage during which bacteria are labeled with a DNA-specific fluorophore,
      and finally recovery of bacteria on the surface of a black membrane for analysis
      using the Scansystem. The entire procedure from sampling to result can be
      completed in 90 min. Both gram-negative and gram-positive bacteria in RBCC are
      detected with a higher sensitivity than with currently available culture-based
      methods. The Scansystem RBC kit is shown to be sensitive enough to identify low
      level bacterial contamination in a single unit tested in a pool of up to 20 RBCC
      samples (detection limit of between 1 and 10 CFU/ml depending on the bacterial
      strain). The method therefore lends itself to incorporation into high-sample
      throughput screening programs.

PMID- 15872252
TI  - Identification of non-Helicobacter pylori spiral organisms in gastric samples
      from humans, dogs, and cats.
AB  - Tightly coiled bacteria are a rare cause of gastric pathology in humans and
      represent a mixture of species for which a zoonotic origin is suspected. Similar
      organisms are common inhabitants of the gastric mucosae of carnivores and pigs.
      It was the goal of the present study to determine the actual occurrence of each
      individual Helicobacter species in human, canine, and feline stomachs in order to
      better understand the possible zoonotic significance. Gastric biopsy samples from
      humans with histological evidence of non-Helicobacter pylori spiral bacteria (n =
      123) and samples from the gastric antrum, corpus, and cardia from dogs (n = 110)
      and cats (n = 43) were subjected to a multiplex PCR, enabling the identification
      of Helicobacter felis, Helicobacter bizzozeronii, Helicobacter salomonis, and
      "Candidatus Helicobacter suis." A PCR for detecting H. pylori was applied to all
      human samples. Single infections with "Candidatus Helicobacter suis," H. felis,
      H. bizzozeronii, H. salomonis, a hitherto unknown genotype of a non-H. pylori
      spiral organism (Helicobacter-like organism 135 [HLO135]), and H. pylori were
      identified in 30.9%, 8.9%, 2.4%, 11.4%, 7.3%, and 8.9% of the human biopsy
      samples, respectively. Mixed infections (16.3%) with two or even three of these
      were also found. In the canine stomach, H. bizzozeronii (70.0%) was encountered
      as the main spiral organism, while H. felis (62.7%) and HLO135 (67.4%) were the
      predominant Helicobacter species found in the feline gastric mucosa. Although the
      majority of human non-H. pylori organisms are Helicobacter species naturally
      occurring in the stomachs of pigs, cats, and dogs, the frequent identification of
      H. salomonis in human gastric biopsy samples is in contrast to its rare
      identification in pet carnivore samples, urging us to suspect other sources of
      infection.

PMID- 15872253
TI  - Characterization of AmpC-mediated resistance in clinical Salmonella isolates
      recovered from humans during the period 1992 to 2003 in England and Wales.
AB  - The increase in AmpC-mediated resistance in salmonellae constitutes a serious
      public health concern, since these enzymes confer resistance to a wide range of
      beta-lactams. One hundred six isolates were selected from 278,308 Salmonella
      isolates based on resistance to ampicillin and cephalosporins and were subjected
      to further characterization. Nine isolates had a cefoxitin inhibition diameter <
      or = 17 mm and were proven to be AmpC positive by multiplex PCR. Sequence
      analysis revealed the presence of bla(DHA-1), bla(CMY-2), and bla(CMY-4) genes.
      All nine isolates presented different pulsed-field gel electrophoresis
      restriction profiles. The AmpC genetic determinants were present in transferable
      plasmids of around 11, 42, 70, 98, and 99 MDa. A combination of size and
      restriction fragment length polymorphism (RFLP) analysis showed that all the
      bla(CMY) plasmids investigated in our study were different, which suggests that
      bla(CMY) may be located in different plasmid environments. Some United Kingdom
      isolates linked to foreign travel showed RFLP plasmid patterns consistent with
      plasmids previously seen in the United States, which suggests that bla(CMY-2) has
      also been disseminated through plasmid transfer. The fact that two of the
      domestically acquired United Kingdom isolates presented previously unseen RFLP
      plasmid patterns could indicate that these strains have followed routes different
      from those prevalent in North America or other parts of the world. This study
      represents the first report of bla(CMY) genes in Salmonella isolates in the
      United Kingdom and the first report of CMY-4 in Salmonella enterica serotype
      Senftenberg worldwide.

PMID- 15872254
TI  - Genetic and antigenic variability of human respiratory syncytial virus (groups a
      and b) isolated over seven consecutive seasons in Argentina (1995 to 2001).
AB  - The genetic and antigenic variability of human respiratory syncytial virus (HRSV)
      strains isolated in Buenos Aires from 1995 to 2001 was evaluated by partial
      nucleotide sequencing of the G gene and enzyme-linked immunosorbent assay
      analysis with anti-G monoclonal antibodies. Phylogenetic analyses showed that 37
      group A strains clustered into five genotypes, whereas 20 group B strains
      clustered into three genotypes. Group A showed more genetic variability than
      group B. A close correlation between genotypes and antigenic patterns was
      observed. Changes detected in the G protein of viruses from both groups included
      (i) amino acid substitutions and(ii) differences in protein length due to either
      changes in stop codon usage or sequence duplications. Three B strains from 1999
      exhibited a duplication of 20 amino acids, while one B strain from 2001 had 2
      amino acids duplicated. The comparison among Argentinean HRSV strains and viruses
      isolated in other geographical areas during different epidemics is discussed.

PMID- 15872255
TI  - Role and significance of quantitative urine cultures in diagnosis of melioidosis.
AB  - Melioidosis is associated with significant mortality in countries in which it is
      endemic. Previous studies have demonstrated that quantitative Burkholderia
      pseudomallei counts in blood are predictive of mortality. Here we examine the
      relationship between outcomes and quantitative B. pseudomallei counts in urine. A
      total of 755 patients presenting to Sappasithiprasong Hospital, Ubon Ratchathani,
      northeast Thailand (in the northeast part of the country), with melioidosis
      between July 1993 and October 2003 had quantitative urine cultures performed
      within 72 h of admission. Urine culture results were divided into the following
      groups: (i) no growth of B. pseudomallei from a neat sample or pellet, (ii)
      positive result from a centrifuged pellet only (< 10(3) CFU/ml), (iii) detection
      of between 10(3) CFU/ml and 10(5) CFU/ml from a neat sample, or (iv) detection of
      > or = 10(5) CFU/ml from a neat sample. The overall in-hospital mortality rate
      was 45%. Patients with negative urine cultures had the lowest death rate (39%).
      Mortality rates rose with increasing B. pseudomallei counts in urine, from 58%
      for those with positive spun pellets only to 61% for those with between 10(3)
      CFU/ml and 10(5) CFU/ml and 71% for those with > or = 10(5) CFU/ml. This was
      independent of age, presence of bacteremia, known risk factors for melioidosis
      such as diabetes, and the prior administration of antibiotics. The presence of B.
      pseudomallei in urine during systemic infection is associated with a poor
      prognosis.

PMID- 15872256
TI  - Evaluation of 12 commercial tests and the complement fixation test for Mycoplasma
      pneumoniae-specific immunoglobulin G (IgG) and IgM antibodies, with PCR used as
      the "gold standard".
AB  - Serology and nucleic acid amplification are the main diagnostic tools for the
      diagnosis of Mycoplasma pneumoniae infection. Since no reference standard is
      generally accepted, serologic assays for M. pneumoniae have not been evaluated on
      a broad scale. In this study, 12 commercially available serologic assays (for
      immunoglobulin G [IgG] and IgM) and the complement fixation test (CFT) were
      evaluated by using M. pneumoniae DNA detection by real-time PCR as the "gold
      standard." The assays tested were Platelia EIA (Bio-Rad), SeroMP EIA (Savyon),
      Serion classic EIA (Virion/Serion), Biotest EIA (Biotest), Ridascreen EIA (r
      Biopharm), AniLabsystems EIA (Labsystems), Novum EIA (Novum Diagnostica),
      Diagnosys EIA (MP products), Genzyme/Virotech EIA, ImmunoWell EIA (Genbio),
      ImmunoCard EIA (Meridian), and SerodiaMycoII microparticle agglutination
      (Fujirebio). Serum samples (n = 46) from 27 PCR-positive patients with a known
      first day of disease and sera (n = 33) from PCR-negative controls were obtained
      from prospective studies of acute lower respiratory tract infections.
      Additionally, control sera (n = 63) from patients with acute viral or bacterial
      respiratory infections other than those caused by M. pneumoniae were tested. The
      results showed low specificities for both the Novum and the ImmunoCard IgM
      assays. The IgM assays with the best performances in terms of sensitivity and
      specificity were AniLabsystems (77% and 92%, respectively), SeroMP (71% and 88%,
      respectively), and CFT (65% and 97%, respectively). Good receiver operating
      characteristic areas under the curve were found for CFT (0.94), the Platelia
      assay (0.87), and the AniLabsystems assay (0.85). We conclude that there are few
      commercial serologic assays for the detection of M. pneumoniae infections with
      appropriate performances in terms of sensitivity and specificity and that PCR has
      become increasingly important for the diagnosis of M. pneumoniae infections in
      defined groups of patients.

PMID- 15872257
TI  - Comparison of genotypic and phenotypic methods for species-level identification
      of clinical isolates of coagulase-negative staphylococci.
AB  - To compare commonly used phenotypic methods with genotypic identification methods
      47 clinical isolates of coagulase-negative staphylococci (CONS), 10 CONS ATCC
      strains, and a Staphylococcus aureus clinical isolate were identified using the
      API Staph ID test, BD Phoenix Automated Microbiology System, and 16S rRNA gene
      and tuf gene sequencing. When necessary part of the sodA gene was sequenced for
      definitive identification. The results show that tuf gene sequencing is the best
      method for identification of CONS, but the API Staph ID test is a reasonably
      reliable phenotypic alternative. The performance of the BD Phoenix Automated
      Microbiology System for identification of CONS is poor. The present study also
      showed that although genotypic methods are clearly superior to phenotypic
      identifications, a drawback of sequence-based genotypic methods may be a lack of
      quality of deposited sequences in data banks. In particular, 16S rRNA gene
      sequencing suffers from the lack of high quality among sequences deposited in
      GenBank. Furthermore, genotypic identification based on 16S rRNA sequences has
      limited discriminating power for closely related Staphylococcus species. We
      propose partial sequencing of the tuf gene as a reliable and reproducible method
      for identification of CONS species.

PMID- 15872258
TI  - Microarray-based detection of 90 antibiotic resistance genes of gram-positive
      bacteria.
AB  - A disposable microarray was developed for detection of up to 90 antibiotic
      resistance genes in gram-positive bacteria by hybridization. Each antibiotic
      resistance gene is represented by two specific oligonucleotides chosen from
      consensus sequences of gene families, except for nine genes for which only one
      specific oligonucleotide could be developed. A total of 137 oligonucleotides (26
      to 33 nucleotides in length with similar physicochemical parameters) were spotted
      onto the microarray. The microarrays (ArrayTubes) were hybridized with 36 strains
      carrying specific antibiotic resistance genes that allowed testing of the
      sensitivity and specificity of 125 oligonucleotides. Among these were well
      characterized multidrug-resistant strains of Enterococcus faecalis, Enterococcus
      faecium, and Lactococcus lactis and an avirulent strain of Bacillus anthracis
      harboring the broad-host-range resistance plasmid pRE25. Analysis of two
      multidrug-resistant field strains allowed the detection of 12 different
      antibiotic resistance genes in a Staphylococcus haemolyticus strain isolated from
      mastitis milk and 6 resistance genes in a Clostridium perfringens strain isolated
      from a calf. In both cases, the microarray genotyping corresponded to the
      phenotype of the strains. The ArrayTube platform presents the advantage of
      rapidly screening bacteria for the presence of antibiotic resistance genes known
      in gram-positive bacteria. This technology has a large potential for applications
      in basic research, food safety, and surveillance programs for antimicrobial
      resistance.

PMID- 15872259
TI  - Molecular characterization of vancomycin-resistant Enterococcus faecium isolates
      from Korea.
AB  - A total of 98 vancomycin-resistant Enterococcus faecium (VREF) isolates from four
      tertiary-care hospitals in Korea during the period between 1998 and 2004 were
      analyzed for genotypic characteristics using the multiplex PCR, multilocus
      sequence typing (MLST), pulsed-field gel electrophoresis (PFGE), and esp gene
      analysis. Ninety-two isolates of VREF with VanA phenotype and five of six
      isolates with VanB phenotype possessed the vanA gene. MLST analysis revealed 9
      sequence types (STs), which belonged to a single clonal complex (CC78, clonal
      lineage C1). Five strains showing incongruence between phenotype and genotype
      (VanB-vanA) did not belong to the same genotypic clone. The esp gene was detected
      in all VREF strains, showing 12 different esp repeat profiles. Data suggest that
      an epidemic clonal group of VREF, CC78 with esp gene, is also present in Asia and
      has differentiated into multiple diverse genotypic clones during the evolutionary
      process.

PMID- 15872260
TI  - Rapid and accurate identification of human isolates of Pasteurella and related
      species by sequencing the sodA gene.
AB  - The identification of Pasteurella and related bacteria remains a challenge. Here,
      a 449- to 473-bp fragment (sodA(int)) internal to the sodA gene, encoding the
      manganese-dependent superoxide dismutase, was amplified and sequenced with a
      single pair of degenerate primers from the type strains of Pasteurella (18
      strains), Gallibacterium (1 strain), and Mannheimia (5 strains) species. The
      sodA(int)-based phylogenetic tree was in general agreement with that inferred
      from the analysis of the corresponding 16S rRNA gene sequences, with members of
      the Pasteurella sensu stricto cluster (Pasteurella multocida, Pasteurella canis,
      Pasteurella dagmatis, and Pasteurella stomatis) forming a monophyletic group and
      Gallibacterium and Mannheimia being independent monophyletic genera. However, the
      sodA(int) sequences showed a markedly higher divergence than the corresponding
      16S rRNA genes, confirming that sodA is a potent target to differentiate related
      species. Thirty-three independent human clinical isolates phenotypically assigned
      to 13 Pasteurella species by a reference laboratory were successfully identified
      by comparing their sodA(int) sequences to those of the type species. In the
      course of this work, we identified the first Gallibacterium anatis isolate ever
      reported from a human clinical specimen. The sodA(int) sequences of the clinical
      isolates displayed less than 2.5% divergence from those of the corresponding type
      strains, except for the Pasteurella pneumotropica isolates, which were closely
      related to each other (> 98% sodA(int) sequence identity) but shared only 92%
      sodA(int) identity with the type strain. The method described here provides a
      rapid and accurate tool for species identification of Pasteurella isolates when
      access to a sequencing facility is available.

PMID- 15872261
TI  - Extended multilocus sequence typing system for Campylobacter coli, C. lari, C.
      upsaliensis, and C. helveticus.
AB  - A multilocus sequence typing (MLST) system has been reported previously for
      Campylobacter jejuni to both differentiate strains and identify clonal lineages.
      However, sequence variation at the MLST loci prevents its use for closely related
      Campylobacter species. We describe herein an expanded MLST method to include
      three clinically relevant Campylobacter species, C. coli, C. lari, and C.
      upsaliensis, and a fourth Campylobacter species, C. helveticus. The C. coli and
      C. helveticus methods use the same seven C. jejuni loci (aspA, atpA, glnA, gltA,
      glyA, pgm, and tkt); however, adk and pgi were substituted for aspA and gltA in
      C. lari and for gltA and pgm in C. upsaliensis. Multiple C. coli (n = 57), C.
      lari (n = 20), C. upsaliensis (n = 78), and C. helveticus (n = 9) isolates,
      representing both clinical and environmental sources, were typed. All four
      species were genetically diverse: the majority (> 80%) of the isolates had unique
      sequence types (STs). Using this method, mixed C. lari, C. upsaliensis, and C.
      helveticus isolates were identified; upon separation, each isolate was shown to
      contain two strains of the same species with distinct STs. Additionally, the
      expanded MLST method was able to detect potential lateral transfer events between
      C. jejuni and either C. coli or C. lari and between C. upsaliensis and C.
      helveticus. Thus, the expanded MLST method will prove useful in differentiating
      strains of five Campylobacter species, identifying mixed Campylobacter cultures,
      and detecting genetic exchange within the genus.

PMID- 15872262
TI  - Genomic diversity in Campylobacter jejuni: identification of C. jejuni 81-176
      specific genes.
AB  - Since the publication of the complete genomic sequence of Campylobacter jejuni
      NCTC 11168 in February 2000, evidence has been compiling that suggests C. jejuni
      strains exhibit high genomic diversity. In order to investigate this diversity,
      the unique genomic DNA sequences from a nonsequenced Campylobacter strain, C.
      jejuni 81-176, were identified by comparison with C. jejuni NCTC 11168 by using a
      shotgun DNA microarray approach. Up to 63 kb of new chromosomal DNA sequences
      unique to this pathogen were obtained. Eighty-six open reading frames were
      identified by the presence of uninterrupted coding regions encoding a minimum of
      40 amino acids. In addition, this study shows that the whole-plasmid shotgun
      microarray approach is effective and provides a comprehensive coverage of DNA
      regions that differ between two closely related genomes. The two plasmids
      harbored by this Campylobacter strain, pTet and pVir, were also sequenced, with
      coverages of 2.5- and 2.9-fold, respectively, representing 72 and 92% of their
      complete nucleotide sequences. The unique chromosomal genes encode proteins
      involved in capsule and lipooligosaccharide biosynthesis, restriction and
      modification systems, and respiratory metabolism. Several of these unique genes
      are likely associated with C. jejuni 81-176 fitness and virulence. Interestingly,
      the comparison of C. jejuni 81-176 unique genes with those of C. jejuni ATCC
      43431 revealed a single gene which encodes a probable TraG-like protein. The
      product of this gene might be associated with the mechanism of C. jejuni invasion
      into epithelial cells. In conclusion, this study extends the repertoire of C.
      jejuni genes and thus will permit the construction of a composite and more
      comprehensive microarray of C. jejuni.

PMID- 15872263
TI  - Rapid and sensitive detection of severe acute respiratory syndrome coronavirus by
      rolling circle amplification.
AB  - The severe acute respiratory syndrome (SARS) epidemic of 2003 was responsible for
      774 deaths and caused significant economic damage worldwide. Since July 2003, a
      number of SARS cases have occurred in China, raising the possibility of future
      epidemics. We describe here a rapid, sensitive, and highly efficient assay for
      the detection of SARS coronavirus (SARS-CoV) in cultured material and a small
      number (n = 7) of clinical samples. Using rolling circle amplification (RCA), we
      were able to achieve sensitive detection levels of SARS-CoV RNA in both solid and
      liquid phases. The main advantage of RCA is that it can be performed under
      isothermal conditions with minimal reagents and avoids the generation of false
      positive results, a problem that is frequently encountered in PCR-based assays.
      Furthermore, the RCA technology provides a faster, more sensitive, and economical
      option to currently available PCR-based methods.

PMID- 15872264
TI  - Detection and characterization of new influenza B virus variants in 2002.
AB  - One-hundred five influenza B-positive specimens obtained from southeast Asia in
      2002 were categorized on the basis of DNA sequencing of HA1 gene as well as real
      time PCR analysis of the NA gene. Phylogenetic analysis of the HA1 gene sequences
      showed that the majority of the viruses (96.2%) belonged to the B/Victoria/2/87
      lineage, while a smaller percentage of the viruses (3.8%) belonged to the
      B/Yamagata/16/88 lineage. The B/Yamagata/16/88 viruses displayed significant
      antigenic drift in the deduced amino acid sequences of the HA1 protein, and the
      B/Victoria/2/87-like viruses consisted of B/Hong Kong/1351/02-like (72.3%) and
      B/Hong Kong/330/01-like (27.7%) viruses. The B/Hong Kong/1351/02-like viruses
      were reassortants with the HA gene belonging to the B/Victoria/2/87 lineage and
      the NA gene belonging to the B/Yamagata/16/88 lineage, whereas both the HA and NA
      genes of B/Hong Kong/330/01 virus belonged to the B/Victoria/2/87 lineage. In
      this study, however, all the B/Hong Kong/330/01-like isolates exhibited the
      B/Yamagata/16/88-like NA gene, which likely resulted from reassortment of B/Hong
      Kong/330/01 and B/Hong Kong/1351/02 viruses during coinfection. Additional
      molecular characterization of the six internal genes showed that the M, NS, PA,
      and PB2 genes of the new variants were B/Hong Kong/1351/02 in origin, whereas the
      NP and PA genes retained the B/Hong Kong/330/01 origin. Interestingly, these new
      variants all appeared late in the year 2002. These results support the notion
      that influenza B viruses continued to evolve through antigenic drift and shift.

PMID- 15872265
TI  - Microbiological aspects of the investigation that traced the 1998 outbreak of
      listeriosis in the United States to contaminated hot dogs and establishment of
      molecular subtyping-based surveillance for Listeria monocytogenes in the PulseNet
      network.
AB  - A multistate outbreak of listeriosis occurred in the United States in 1998 with
      illness onset dates between August and December. The outbreak caused illness in
      108 persons residing in 24 states and caused 14 deaths and four miscarriages or
      stillbirths. This outbreak was detected by public health officials in Tennessee
      and New York who observed significant increases over expected listeriosis cases
      in their states. Subsequently, the Centers for Disease Control and Prevention
      (CDC) began laboratory characterization of clinical isolates of Listeria
      monocytogenes by serotyping and restriction fragment length polymorphism analysis
      using pulsed-field gel electrophoresis (PFGE). For the purpose of this
      investigation, outbreak-related isolates were defined as those that had a
      specific AscI-PFGE pattern and indistinguishable or highly similar (no more than
      2 band difference in 26 bands) ApaI-PFGE patterns when their DNA was restricted
      by AscI and ApaI restriction enzymes. Timely availability of molecular subtyping
      results enabled epidemiologists to separate outbreak cases from temporally
      associated sporadic cases in the same geographic areas and facilitated the
      identification of contaminated hot dogs manufactured at a single commercial
      facility as the source of the outbreak. During the investigation of this
      outbreak, a standardized protocol for subtyping L. monocytogenes by PFGE was
      developed and disseminated to public health laboratories participating with CDC's
      PulseNet network; these laboratories were requested to begin routine PFGE
      subtyping of L. monocytogenes.

PMID- 15872266
TI  - Comparison of a real-time reverse transcriptase PCR assay and a culture technique
      for quantitative assessment of viral load in children naturally infected with
      respiratory syncytial virus.
AB  - Respiratory syncytial virus (RSV) is the most common cause of lower respiratory
      infection of children. Understanding RSV pathogenesis and evaluating
      interventions requires quantitative RSV testing. Previous studies have used the
      plaque assay technique. Real-time reverse transcriptase PCR (RTrtPCR) offers
      possible greater sensitivity, stability after freeze/thaw, and lower cost, thus
      facilitating multicenter studies. We developed RTrtPCR assays based upon the RSV
      N and F genes. The N-gene assay detected greater RSV quantity and was further
      evaluated. Standard curves utilized both extractions from RSV culture
      supernatants of known quantity and cloned purified copies of the target DNA. In
      vitro, the ratio of RSV subgroup A (RSV-A) genome copies to PFU was 153:1. A
      total of 462 samples collected quantitatively from 259 children were analyzed in
      duplicate by RTrtPCR. Results were compared with those of RSV plaque assays
      performed on fresh aliquots from the same children. Duplicate RTrtPCR results
      were highly correlated (r2 = 0.9964). The mean viral load from nasal washes
      obtained on the first study day was 5.75 +/- standard error of the mean 0.09 log
      PFU equivalents (PFUe)/ml. Viral load by RTrtPCR correlated with plaque assay
      results (r2 = 0.158; P < 0.0001). Within individuals, upper and lower respiratory
      tract secretions contained similar viral concentrations. RSV-A-infected children
      had 1.17 log PFUe higher viral loads than did those with RSV-B (P < 0.0001). RSV
      quantification by RTrtPCR of the N gene is precise and has significant, though
      limited, correlation with quantitative culture. The utility of the RTrtPCR
      quantification technique for clinical studies would be solidified after its
      correlation with RSV disease severity is established.

PMID- 15872267
TI  - Quantification of hepatitis delta virus RNA in serum by consensus real-time PCR
      indicates different patterns of virological response to interferon therapy in
      chronically infected patients.
AB  - Hepatitis delta virus (HDV), in association with hepatitis B virus, is
      responsible for severe acute and chronic hepatitis. Treatment of the infection
      relies on the long-term administration of high doses of alpha interferon (IFN),
      and the treatment efficiency is monitored by the detection of anti-HDV
      immunoglobulin M and HDV genome in serum. Like the case for other chronic viral
      infections, HDV genome quantification in serum should be useful for the follow-up
      of infected patients. The aims of this study were to develop a quantitative assay
      for the detection of any type of HDV in serum and to evaluate the benefit of HDV
      RNA quantification for the follow-up of chronically infected patients receiving
      IFN. A real-time reverse transcription-PCR assay was developed to quantify the
      HDV RNA load in serum. Its efficacy was evaluated with 160 serum samples, 76 of
      which were collected from 11 chronically infected patients who were treated with
      pegylated IFN. The assay was sensitive (100 copies/ml of serum) and efficient for
      all HDV types, including type 3 and the recently described types 5, 6, and 7. The
      viral load determinations for treated patients allowed us to identify different
      profiles of virological responses to IFN therapy with more accuracy than that
      attainable with the qualitative approach. In conclusion, we have developed a
      quantitative HDV RNA assay for serum which is adapted to the follow-up of
      antiviral treatment for patients infected with any HDV type. The assay will help
      us to understand the natural history of HDV infection and to define guidelines
      for the management of chronic delta hepatitis.

PMID- 15872268
TI  - Characterization of oral strains of Cardiobacterium valvarum and emended
      description of the organism.
AB  - The description of the new species Cardiobacterium valvarum prompted a search for
      additional strains of the organism. Here we report characterization of four oral
      Cardiobacterium strains from the Culture Collection of the University of
      Goteborg. The 16S rRNA gene sequences of the organisms exhibited 99.6% to 99.3%
      homology with Cardiobacterium valvarum. The cellular fatty acid profiles,
      electrophoretic patterns of whole-cell proteins, growth rate and nutritional
      requirement, colonial and cellular morphology, and biochemical reactions were
      also similar to those of C. valvarum. These results thus classify these organisms
      as oral strains of C. valvarum. All strains were susceptible to many antibiotics
      tested. The description of the species was emended. C. valvarum is a rare cause
      of endocarditis, and its relationship with periodontal diseases may need
      investigation.

PMID- 15872269
TI  - Detection of Cyclospora cayetanensis oocysts in human fecal specimens by flow
      cytometry.
AB  - A diagnosis of cyclosporiasis typically involves stool examinations for the
      presence of Cyclospora oocysts by means of microscopy. In recent years, flow
      cytometry has been gaining in popularity as a novel method of detecting pathogens
      in environmental and clinical samples. The present study is an evaluation of a
      flow cytometric method for the detection and enumeration of Cyclospora oocysts in
      human fecal specimens associated with food-borne outbreaks of cyclosporiasis in
      Ontario, Canada. Flow cytometry results were generally very comparable to the
      original microscopy results for these specimens, in terms of both presence or
      absence of oocysts and relative oocyst concentrations. Of the 34 fecal specimens
      confirmed positive for Cyclospora by microscopy, 32 were also found positive by
      flow cytometry, and 2 others were considered equivocal. Of the eight fecal
      specimens reported to be negative by microscopy, two were found positive by flow
      cytometry and five others were considered equivocal. These two flow cytometry
      positive samples and one of the equivocal samples were confirmed by microscopic
      reexamination, suggesting that flow cytometry may be more sensitive than
      microscopy. While the sample preparation time for flow cytometry is similar to or
      slightly longer than that for microscopy, the actual analysis time is much
      shorter. Further, because flow cytometry is largely automated, an analyst's
      levels of fatigue and expertise will not influence results. Flow cytometry
      appears to be a useful alternative to microscopy for the screening of large
      numbers of stool specimens for Cyclospora oocysts, such as in an outbreak
      situation.

PMID- 15872270
TI  - Genetic background affects stability of mecA in Staphylococcus aureus.
AB  - The staphylococcal methicillin resistance determinant, mecA, resides on a mobile
      genetic element, staphylococcus chromosomal cassette mec (SCCmec). The
      distribution of SCCmec in nature is limited to relatively few clonal complexes of
      related methicillin-resistant Staphylococcus aureus (MRSA). We have previously
      reported that some genetic backgrounds are restrictive of mecA and penicillin
      binding protein 2a expression, which could account for the restricted clonal
      distribution of SCCmec in nature. In this study, we investigate the potential
      role of the host chromosome in the transformability and expression of mecA in 103
      naturally occurring methicillin-susceptible S. aureus clinical isolates. The
      isolates, which had been genotyped previously by multilocus sequence typing, were
      classified into one of two mutually exclusive categories based on whether the
      isolates belonged to "major" MRSA lineages or to "other" lineages that are never
      or occasionally MRSA. We introduced mecA expressed on the low-copy-number plasmid
      pYK20 into each MSSA strain and assayed the phenotype of resistance to nafcillin
      by population analysis to assess the relationship between the stability of mecA
      expression and genetic background. Strains from the major MRSA lineages were more
      transformable with pYK20 and better able to maintain the plasmid and express
      resistance in comparison to strains from other lineages. These data support the
      hypothesis that the presence of mecA within relatively few clonal complexes is
      partly due to genetic factors that are permissive of mecA and its gene product.

PMID- 15872271
TI  - Staphylococcus aureus isolates carrying Panton-Valentine leucocidin genes in
      England and Wales: frequency, characterization, and association with clinical
      disease.
AB  - Staphylococcus aureus isolates carrying the genes that encode for Panton
      Valentine leucocidin (PVL), a highly potent toxin, have been responsible for
      recent outbreaks of severe invasive disease in previously healthy children and
      adults in the United States of America and Europe. To determine the frequency of
      PVL-positive isolates sent to the Staphylococcus Reference Unit (United Kingdom)
      for epidemiological purposes, we tested 515 isolates of S. aureus, and 8 (1.6%)
      were positive for the PVL locus. A further 470 isolates were selected to explore
      the association of PVL-positive S. aureus with clinical disease. Of these, 23
      (4.9%) were PVL positive and most were associated with skin and soft tissue
      infections (especially abscesses). The PVL genes were also detected in isolates
      responsible for community-acquired pneumonia, burn infections, bacteremia, and
      scalded skin syndrome. Genotyping by pulsed-field gel electrophoresis and
      multilocus sequence typing revealed that the PVL-positive isolates were from
      diverse genetic backgrounds, although one prevalent clone of 12 geographically
      dispersed methicillin-resistant S. aureus (MRSA) isolates was identified (ST80).
      All 12 isolates were stapylococcal cassette chromosome mec type IVc, had an agr3
      allele, and shared a common toxin gene profile (sea-see, seg-sej, eta, etb, and
      tst negative but etd positive). ST80 strains with similar genetic characteristics
      have been responsible for community-acquired infections in France and
      Switzerland. The remaining PVL-positive isolates were mostly methicillin
      sensitive S. aureus and belonged to 12 different sequence types, including ST22
      and ST30, which are closely related to the most prevalent MRSA clones in United
      Kingdom hospitals, EMRSA-15 and EMRSA-16, respectively.

PMID- 15872272
TI  - Effect of sequence polymorphisms on performance of two real-time PCR assays for
      detection of herpes simplex virus.
AB  - Herpes simplex virus (HSV) is the most common cause of acquired, sporadic
      encephalitis in the United States. PCR identification of HSV in spinal fluid has
      become the diagnostic gold standard due to its sensitivity and potential for
      speed, replacing other methods such as culture. We developed a real-time PCR
      assay to detect HSV, using a new type of hybridization probe, the Eclipse probe.
      In this study, we ran 323 samples (171 positives and 152 negatives) with the
      Eclipse real-time PCR assay and compared these results with another PCR assay
      using gel detection. The real-time assay agreed with our reference method for 319
      out of the 323 samples tested (99%). Using two different real-time PCR platforms,
      we discovered that SNPs within the amplicon's probe binding region that are used
      to distinguish HSV-1 from HSV-2 can decrease assay sensitivity. This problem is
      potentially a general one for assays using fluorescent probes to detect target
      amplification in a real-time format. While real-time PCR can be a powerful tool
      in the field of infectious disease, careful sequence evaluation and clinical
      validation are essential in creating an effective assay.

PMID- 15872273
TI  - Preclinical and clinical performance of the Efoora test, a rapid test for
      detection of human immunodeficiency virus-specific antibodies.
AB  - Barriers to effective diagnostic testing for human immunodeficiency virus type 1
      (HIV-1) infection can be reduced with simple, reliable, and rapid detection
      methods. Our objective was to determine the accuracy, sensitivity, and
      specificity of a new rapid, lateral-flow immunochromatographic HIV-1 antibody
      detection device. Preclinical studies were performed using seroconversion, cross
      reaction, and interference panels, archived clinical specimens, and fresh whole
      blood. In a multicenter, prospective clinical trial, a four-sample matrix of
      capillary (fingerstick) whole-blood specimens and venous whole blood, plasma, and
      serum was tested for HIV-1 antibodies with the Efoora HIV rapid test (Efoora
      Inc., Buffalo Grove, IL) and compared with an enzyme immunoassay (EIA) (Abbott
      Laboratories) licensed by the Food and Drug Administration. Western blot and
      nucleic acid test supplemental assays were employed to adjudicate discordant
      samples. Preclinical testing of seroconversion panels showed that antibodies were
      often detected earlier by the rapid test than by a reference EIA. No significant
      interference or cross-reactions were observed. Testing of 4,984 archived
      specimens yielded a sensitivity of 99.2% and a specificity of 99.7%. A
      prospective multicenter clinical study with 2,954 adult volunteers demonstrated
      sensitivity and specificity for the Efoora HIV rapid test of 99.8% (95%
      confidence interval [CI], 99.3 and 99.98%) and 99.0% (95% CI, 98.5 and 99.4%),
      respectively. Reactive rapid HIV-1 antibody detection was confirmed in 99.6% of
      those with a known HIV infection (n = 939), 5.2% of those in the high-risk group
      (n = 1,003), and 0.1% of those in the low-risk group (n = 1,012). For 21 (0.71%)
      patients, there was discordance between the results of the rapid test and the
      confirmatory EIA/Western blot tests. We conclude that the Efoora HIV rapid test
      is a simple, rapid assay for detection of HIV-1 antibodies, with high sensitivity
      and specificity compared to a standardized HIV-1 EIA.

PMID- 15872274
TI  - Multilocus sequence typing of Streptococcus uberis provides sensitive and
      epidemiologically relevant subtype information and reveals positive selection in
      the virulence gene pauA.
AB  - Control of the bovine mastitis pathogen Streptococcus uberis requires sensitive
      and epidemiologically meaningful subtyping methods that can provide insight into
      this pathogen's epidemiology and evolution. Development of a multilocus sequence
      typing (MLST) scheme based on six housekeeping and virulence genes allowed
      differentiation of 40 sequence types among 50 S. uberis isolates from the United
      States (n = 30) and The Netherlands (n = 20). MLST was more discriminatory than
      EcoRI or PvuII ribotyping and provided subtype data with better epidemiological
      relevance, e.g., by discriminating isolates with identical ribotypes obtained
      from different farms. Phylogenetic analyses of MLST data revealed indications of
      reticulate evolution between genes, preventing construction of a core phylogeny
      based on concatenated DNA sequences. However, all individual gene phylogenies
      clearly identified a distinct pauA-negative subtaxon of S. uberis for which
      housekeeping alleles closely resembled those of Streptococcus parauberis. While
      the average GC content for five genes characterized was between 0.38 and 0.40,
      pauA showed a considerably lower GC content (0.34), suggesting acquisition
      through horizontal transfer. pauA also showed a higher nonsynonymous/synonymous
      rate ratio (dN/dS) (1.2) compared to the other genes sequenced (dN/dS < 0.12),
      indicating positive selection in this virulence gene. In conclusion, our data
      show that (i) MLST provides for highly discriminatory and epidemiologically
      relevant subtyping of S. uberis; (ii) S. uberis has a recombinatorial population
      structure; (iii) phylogenetic analysis of MLST data reveals an S. uberis subtaxon
      resembling S. parauberis; and (iv) horizontal gene transfer and positive
      selection contribute to evolution of certain S. uberis genes, such as the
      virulence gene pauA.

PMID- 15872275
TI  - Loop-mediated isothermal amplification method for rapid detection of the
      periodontopathic bacteria Porphyromonas gingivalis, Tannerella forsythia, and
      Treponema denticola.
AB  - Loop-mediated isothermal amplification (LAMP), a novel nucleic acid amplification
      method, was developed for the rapid detection of the major periodontal pathogens
      Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. The LAMP
      method amplifies DNA with high specificity, efficiency, and rapidity under
      isothermal conditions using a set of four specially designed primers and a DNA
      polymerase with strand displacement activity. In this study, we initially
      designed the primers for LAMP assays to detect these bacteria and evaluated the
      specificity and sensitivity of these assays. The specificities of the primers for
      these bacteria were examined using various oral bacteria and various reaction
      times. The lower detection limits of the 60-min LAMP reaction without loop
      primers were 1 microg/tube for P. gingivalis, 10 fg/tube for T. forsythia, and 1
      ng/tube for T. denticola. Addition of the loop primers for each bacterium
      improved the detection specificities and sensitivities by several magnitudes.
      Furthermore, LAMP assays were applied to the rapid detection of these periodontal
      pathogens in clinical specimens, and the results were compared with those of
      conventional PCR detection. The results of the LAMP assays corresponded to those
      of conventional PCR assays. These results indicate that the LAMP assay is an
      extremely rapid, highly sensitive, specific method. This method is very useful
      for the rapid detection of periodontopathic bacteria and the diagnosis of
      periodontal disease.

PMID- 15872276
TI  - Prevalence of pathogenicity island IICFT073 genes among extraintestinal clinical
      isolates of Escherichia coli.
AB  - Uropathogenic Escherichia coli is the most common cause of urinary tract
      infection (UTI). Cystitis in women is by far the most common UTI; pyelonephritis
      in both sexes and prostatitis in men are more severe but are less frequent
      complaints. The ability of E. coli to cause UTI is associated with specific
      virulence determinants, some of which are encoded on pathogenicity islands (PAI).
      One such PAI (PAI IICFT073), of the prototypical uropathogenic E. coli strain
      CFT073, contains 116 open reading frames, including iron-regulated genes,
      carbohydrate biosynthetic genes, the serine protease autotransporter picU, a two
      partner secretion system, a type I secretion system, mobility genes, and a large
      number of hypothetical genes. To determine the association of PAI IICFT073 with
      UTI, PCR was used to examine the prevalence of the five virulence-associated loci
      among the ECOR collection and a collection of E. coli isolated from patients with
      cystitis, pyelonephritis, prostatitis, or septicemia. All PAI IICFT073 loci were
      found to be more prevalent among the B2 phylogenetic group than any other group
      within the ECOR collection and among invasive prostatitis strains than were
      cystitis or pyelonephritis strains. These data support the theory that clinical
      isolates causing prostatitis are more virulent than those producing cystitis or
      pyelonephritis in women.

PMID- 15872278
TI  - Interrelationship between polymorphisms of incA, fusogenic properties of
      Chlamydia trachomatis strains, and clinical manifestations in patients in The
      Netherlands.
AB  - IncA variation among Dutch Chlamydia trachomatis isolates was investigated. Of 98
      strains, two carried an incA with a premature stop codon, lacked IncA, and were
      nonfusogenic, while 96 contained an intact incA, expressed IncA, and were
      fusogenic. Among these 96 strains, nine IncA sequence types were found, of which
      the three most frequently encountered (88% of the strains) were randomly
      distributed among symptomatic and asymptomatic patients.

PMID- 15872277
TI  - Real-time PCR for detection and identification of Plasmodium spp.
AB  - Rapid and accurate detection of malaria parasites in blood is needed to institute
      proper therapy. We developed and used a real-time PCR assay to detect and
      distinguish four Plasmodium spp. that cause human disease by using a single
      amplification reaction and melting curve analysis. Consensus primers were used to
      amplify a species-specific region of the multicopy 18S rRNA gene, and SYBR Green
      was used for detection in a LightCycler instrument. Patient specimens infected at
      0.01 to 0.02% parasitemia densities were detected, and analytical sensitivity was
      estimated to be 0.2 genome equivalent per reaction. Melting curve analysis based
      on nucleotide variations within the amplicons provided a basis for accurate
      differentiation of Plasmodium falciparum, P. vivax, P. ovale, and P. malariae.
      For assay validation, 358 patient blood samples from the National University
      Hospital in Singapore and Evanston Northwestern Healthcare in Illinois were
      analyzed. Of 76 blinded patient samples with a microscopic diagnosis of P.
      falciparum, P. vivax, or P. ovale infection, 74 (97.4%) were detected by real
      time PCR, including three specimens containing mixed P. falciparum-P. vivax
      infections. No Plasmodium DNA was amplified in any of the 82 specimens sent for
      malaria testing but that were microscopically negative for Plasmodium infection.
      In addition, 200 blood samples from patients whose blood was collected for
      reasons other than malaria testing were also determined to be negative by real
      time PCR. Real-time PCR with melting curve analysis could be a rapid and
      objective supplement to the examination of Giemsa-stained blood smears and may
      replace microscopy following further validation.

PMID- 15872279
TI  - Immunofluorescence assay for detection of the nucleocapsid antigen of the severe
      acute respiratory syndrome (SARS)-associated coronavirus in cells derived from
      throat wash samples of patients with SARS.
AB  - An antigen detection assay for severe acute respiratory syndrome (SARS)
      coronavirus was established in this study by an indirect immunofluorescence test,
      which utilized cells derived from throat wash samples of patients with SARS and a
      rabbit serum that recognized the nucleocapsid protein of SARS-associated
      coronavirus (SARS-CoV) but not that of other human coronavirus tested. It
      detected SARS-CoV in 11 of 17 (65%) samples from SARS patients as early as day 2
      of illness but in none of the 10 samples from healthy controls. Compared with
      other diagnostic modalities for detecting SARS-CoV, this assay is simpler, more
      convenient, and economical. It could be an alternative for early and rapid
      diagnosis, should SARS return in the future.

PMID- 15872280
TI  - Use of monoclonal antibodies to serotype Bordetella pertussis isolates:
      comparison of results obtained by indirect whole-cell enzyme-linked immunosorbent
      assay and bacterial microagglutination methods.
AB  - Sixty-one Bordetella pertussis isolates were tested blindly in two laboratories
      to determine their serotype nature by monoclonal antibodies using two independent
      methods: the standard bacterial microagglutination assay and an indirect whole
      cell enzyme-linked immunosorbent assay. Both methods gave concordant results in
      60 of the 61 isolates.

PMID- 15872281
TI  - Prevalence of derepressed ampC mutants and extended-spectrum beta-lactamase
      producers among clinical isolates of Citrobacter freundii, Enterobacter spp., and
      Serratia marcescens in Korea: dissemination of CTX-M-3, TEM-52, and SHV-12.
AB  - The resistance mechanism of extended-spectrum cephalosporins in clinical isolates
      of Citrobacter freundii, Enterobacter spp., and Serratia marcescens was studied.
      Of 152 isolates, 45 isolates (29.6%) were derepressed AmpC mutants and 39
      isolates (25.7%) produced extended-spectrum beta-lactamase (ESBLs). The most
      prevalent ESBLs were CTX-M enzymes, followed by TEM-52 and SHV-12.

PMID- 15872282
TI  - Sequencing of the Chlamydophila psittaci ompA gene reveals a new genotype, E/B,
      and the need for a rapid discriminatory genotyping method.
AB  - Twenty-one avian Chlamydophila psittaci isolates from different European
      countries were characterized using ompA restriction fragment length polymorphism,
      ompA sequencing, and major outer membrane protein serotyping. Results reveal the
      presence of a new genotype, E/B, in several European countries and stress the
      need for a discriminatory rapid genotyping method.

PMID- 15872283
TI  - Development and use of an internal positive control for detection of Bordetella
      pertussis by PCR.
AB  - An internal control of amplification was constructed by recombinant PCR to detect
      PCR inhibitors. This exogenous DNA was included in the reaction mixture and
      coamplified with the target gene. This detection was successfully applied to the
      diagnosis of whooping cough by amplification of a fragment of Bordetella
      pertussis IS481.

PMID- 15872284
TI  - Use of a commercial reagent leads to reduced germ tube production by Candida
      dubliniensis.
AB  - The goal of this study was to determine the factor(s) explaining our inability to
      detect Candida dubliniensis. When germ tube-positive yeasts were tested for C.
      dubliniensis, no C. dubliniensis was detected; however, 58 C. dubliniensis
      strains were detected when germ tube-negative Candida albicans strains were
      tested further. Since all 58 C. dubliniensis strains detected were germ tube
      negative, these data implied that false-negative germ tube tests occurred with
      germ tube solution (GTS; Remel, Lenexa, KS). All 41 known C. dubliniensis strains
      tested were negative with GTS, whereas 40 were positive with rabbit serum (RS;
      Sigma-Aldrich, St. Louis, MO). Results for C. albicans were equivalent in GTS and
      RS. In conclusion, GTS cannot be used for the detection of C. dubliniensis, and
      switching from yeast to hyphae in C. dubliniensis is more restricted than in C.
      albicans.

PMID- 15872285
TI  - Identification of Shigella sonnei biotype g isolates carrying class 2 integrons
      in Italy (2001 to 2003).
AB  - Phenotyping and genotyping have been carried out on 64 epidemic and sporadic
      isolates of Shigella sonnei identified in Italy in the years 2001 to 2003. Class
      2 integron carriage has been also investigated. Isolates from four of the five
      outbreaks and four of six sporadic cases were biotype g, pulsed-field gel
      electrophoresis type B, and class 2 integron positive, suggesting emergence and
      spread of an epidemic clone in Italy.

PMID- 15872286
TI  - Comparison of six methods of extracting Mycobacterium tuberculosis DNA from
      processed sputum for testing by quantitative real-time PCR.
AB  - Six methods of extracting Mycobacterium tuberculosis DNA from sputum for testing
      by quantitative PCR were compared: Tris-EDTA (TE) buffer, PrepMan Ultra, 2%
      sodium dodecyl sulfate (SDS)-10% Triton X with and without sonication, Infectio
      Diagnostics, Inc. (IDI) lysing tubes, and QIAGEN QIAamp DNA mini kit; all
      included a 15-min boiling step. Pooled digested and decontaminated sputum was
      spiked with M. tuberculosis ATCC 27294. Each extraction method was repeated eight
      times. Quantitative PCR was performed on the Smart Cycler and Rotor-Gene 3000
      using primers targeting an 83-bp fragment of IS6110. An minor grove binding
      Eclipse probe with a fluorescent label was used for detection. An internal
      control was included to detect amplification inhibition. The limit of detection
      of M. tuberculosis DNA was 0.5 fg with both instruments. Calculated DNA
      concentrations (picograms) extracted using IDI, PrepMan, QIAGEN, and TE were
      42.8, 30.4, 28.2, and 7.4, respectively, when run on the Smart Cycler, and 51.7,
      20.1, 14.9, and 8.6, respectively, when run on Rotor-Gene. All extractions using
      SDS/Triton X with or without sonication were inhibited. Of the extraction methods
      evaluated, IDI lysis tubes provided the greatest yield of mycobacterial DNA, and
      the procedure can be completed in less than 1 h versus 2.5-3 h for the QIAGEN
      extraction.

PMID- 15872287
TI  - Comparative molecular analysis of Haemophilus influenzae isolates from young
      children with acute lower respiratory tract infections and meningitis in Hanoi,
      Vietnam.
AB  - Thirty-seven Haemophilus influenzae strains from nasopharyngeal swabs (NP) and 44
      H. influenzae strains from cerebrospinal fluid (CSF) were investigated. Of the 37
      H. influenzae isolates from NP, the serotypes of 30 isolates were nontypeable, 4
      were type b, 2 were type c, and 1 was type a, whereas all of the 44 isolates from
      CSF were type b. The MICs of 16 antibiotics for the H. influenzae isolates from
      NP and CSF were similar, and no beta-lactamase-negative ampicillin-resistant
      strain was found. Molecular typing by pulsed-field gel electrophoresis (PFGE)
      showed that the 37 H. influenzae strains from NP had 22 PFGE patterns, with none
      predominating, and the 44 H. influenzae strains from CSF had 9 PFGE patterns,
      with patterns alpha (22 isolates) and beta (12 isolates) predominating. Our
      results indicate that two predominant types of H. influenzae type b strains have
      the potential to spread among children with meningitis in Hanoi, Vietnam.

PMID- 15872288
TI  - Efficiency of the ortho VITROS assay for detection of hepatitis C virus-specific
      antibodies increased by elimination of supplemental testing of samples with very
      low sample-to-cutoff ratios.
AB  - The clinical significance of specimens with low sample-to-cutoff (S/Co) ratios in
      the Ortho VITROS chemiluminescence assay (CIA) for detection of antibodies to
      hepatitis C virus (HCV) was evaluated. In one study of 482 CIA-reactive samples,
      none of the 83 samples with S/Co ratios of < 5 was HCV RNA positive. In a
      subsequent study, 332 samples with S/Co ratios of between 1 and 20 were tested
      with the recombinant immunoblot assay (RIBA). None of the 163 samples with S/Co
      ratios of < 5 was RIBA positive, 83% were RIBA negative, and 28 samples (18%)
      were RIBA indeterminate. HCV RNA and/or clinical evidence of hepatitis was not
      found in the 27 indeterminate cases examined. These results show that over 99% of
      samples with very low S/Co ratios (< or = 5) have no evidence of HCV infection.
      Therefore, we suggest that the HCV antibody testing algorithm for the VITROS
      assay might be modified to eliminate supplemental testing of samples with very
      low S/Co ratios.

PMID- 15872289
TI  - Identification and characterization of genomic variations between Mycobacterium
      bovis and M. tuberculosis H37Rv.
AB  - Genetic differences between Mycobacterium bovis and M. tuberculosis were
      identified. We found (i) a deletion of Rv3479 specific to M. bovis, (ii) that the
      rpfA gene is shortened to various extents in M. bovis, and (iii) an insertion in
      Rv0648 and a duplication of lppA common in M. tuberculosis complex isolates.

PMID- 15872290
TI  - Broth microdilution and disk diffusion tests for susceptibility testing of
      Pasteurella species isolated from human clinical specimens.
AB  - Broth microdilution and disk diffusion susceptibility testing were performed on
      73 strains of Pasteurella species isolated from human infections and on five
      American Type Culture Collection strains of Pasteurella species. Both methods
      appear reliable for testing susceptibilities of Pasteurella species.

PMID- 15872291
TI  - Isothermal RNA sequence amplification method for rapid antituberculosis drug
      susceptibility testing of Mycobacterium tuberculosis.
AB  - RNA transcript quantification by an isothermal sequence amplification reaction
      was evaluated for susceptibility testing of 15 Mycobacterium tuberculosis
      strains. Agreement with the proportion method on Ogawa egg medium and the BACTEC
      MGIT 960 system was 100 and 87% for rifampin, 93 and 100% for isoniazid, 60 and
      53% for ethambutol, and 80 and 80% for streptomycin, respectively.

PMID- 15872292
TI  - Clonal spread of pediatric isolates of ciprofloxacin-resistant, emm type 6
      Streptococcus pyogenes.
AB  - Twenty-four community isolates of Streptococcus pyogenes resistant to
      ciprofloxacin and susceptible to levofloxacin, gatifloxacin, and moxifloxacin
      were studied. Sequence determination of the quinolone resistance-determining
      regions in the gyrA and parC genes revealed a T/G mutation in parC leading to a
      Ser79Ala substitution in ParC. All isolates were of the emm type 6, and 18 and 2
      of them were indistinguishable or closely related, respectively, on the basis of
      pulsed-field gel electrophoresis.

PMID- 15872293
TI  - Unstable vancomycin heteroresistance is common among clinical isolates of
      methiciliin-resistant Staphylococcus aureus.
AB  - We tested 109 unique, vancomycin-susceptible, methicillin-resistant
      Staphylococcus aureus (MRSA) strains for vancomycin heteroresistance by a
      selection method, i.e., step-wise exposure of large inoculums to increasing
      concentrations of vancomycin. Although no strains demonstrated stable
      heteroresistance, 81 strains (74%) demonstrated unstable heteroresistance.
      Unstable heteroresistance is common among clinical isolates of MRSA and may
      represent a cause of therapeutic failure.

PMID- 15872294
TI  - Erythromycin-resistant group a streptococcal isolates collected between 2000 and
      2005 in Oahu, Hawaii, and their emm types.
AB  - We examined erythromycin and clindamycin susceptibilities with Etest methodology
      among 546 group A streptococcal isolates collected in Hawaii between February
      2000 and November 2004. Erythromycin resistance was low (3.1%). No isolate was
      clindamycin resistant. The prevalence of erythromycin resistance in group A
      streptococci remains low in Hawaii.

PMID- 15872295
TI  - Distribution of IS1311 and IS1245 in Mycobacterium avium subspecies revisited.
AB  - We demonstrated that IS1245 is not present in Mycobacterium avium subsp.
      paratuberculosis by restriction fragment length polymorphism and that the
      designated three-banded bird pattern of IS1245 in M. avium subsp. avium consists
      of one copy of IS1245 and two copies of IS1311. Cross hybridization between the
      two elements can be avoided by using more specific probes.

PMID- 15872296
TI  - Prevalence, incidence, and clinical relevance of the reverse transcriptase V207I
      mutation outside the YMDD motif of the hepatitis B virus polymerase during
      lamivudine therapy.
AB  - The reverse transcriptase V207I mutation within the hepatitis B virus (HBV)
      polymerase is associated with resistance to lamivudine in vitro. The prevalence
      of this mutation in treatment-naive patients was 1% (1/96). A follow-up of the
      patient carrying this mutation prior to treatment revealed no loss of sensitivity
      of HBV to lamivudine in vivo.

PMID- 15872297
TI  - Routine incubation of BacT/ALERT FA and FN blood culture bottles for more than 3
      days may not be necessary.
AB  - We reviewed time to detection for 35,500 blood cultures collected in BacT/ALERT
      FA and FN bottles. In the first 3 days of incubation, 97.5% of the 2,609
      clinically significant isolates were detected, suggesting that routine incubation
      for more than 3 days may not be necessary for FA and FN bottles.

PMID- 15872298
TI  - Streptococcus pneumoniae antigen test using positive blood culture bottles as an
      alternative method to diagnose pneumococcal bacteremia.
AB  - Recovery of Streptococcus pneumoniae from positive blood culture bottles may be
      difficult due to autolysis of pneumococci. Therefore, we evaluated the
      performance of the Binax NOW S. pneumoniae antigen test with samples from
      positive blood culture bottles and defined the duration of detectable
      pneumococcal antigen in these bottles. Use of the S. pneumoniae antigen test is
      an alternative method for identifying S. pneumoniae from positive blood culture
      bottles and may enable a diagnosis of pneumococcal bacteremia despite negative
      subcultures.

PMID- 15872299
TI  - Oral Campylobacter species involved in extraoral abscess: a report of three
      cases.
AB  - Oral Campylobacter species are rarely reported to cause extraoral infections.
      Here we present three cases of extraoral abscess caused by an oral Campylobacter
      sp. and a Streptococcus sp. The Campylobacter species were all isolated
      anaerobically and identified by sequencing analysis of the 16S rRNA gene. The
      cases included a breast abscess caused by Campylobacter rectus and a non-group A
      beta-hemolytic streptococcus in a patient with lymphoma, a liver abscess caused
      by Campylobacter curvus and an alpha-hemolytic streptococcus in a patient with
      complicated ovarian cancer, and a postobstructive bronchial abscess caused by C.
      curvus and group C beta-hemolytic Streptococcus constellatus in a patient with
      lung cancer. The abscesses were drained or resected, and the patients were
      treated with antibiotics with full resolution of the lesions. The C. curvus cases
      are likely the first reported infections by this organism, and the C. rectus case
      represents the second such reported extraoral infection.

PMID- 15872300
TI  - New species of Bordetella, Bordetella ansorpii sp. nov., isolated from the
      purulent exudate of an epidermal cyst.
AB  - A gram-negative bacillus, SMC-8986(T), which was isolated from the purulent
      exudate of an epidermal cyst but could not be identified by a conventional
      microbiologic method, was characterized by a variety of phenotypic and genotypic
      analyses. Sequences of the 16S rRNA gene revealed that this bacterium belongs to
      the genus Bordetella but diverged distinctly from previously described Bordetella
      species. Analyses of cellular fatty acid composition and performance of
      biochemical tests confirmed that this bacterium is distinct from other Bordetella
      species. Furthermore, the results of comparative sequence analyses of two protein
      coding genes (risA and ompA) also showed that this strain represents a new
      species within the genus Bordetella. Based on the evaluated phenotypic and
      genotypic characteristics, it is proposed that SMC-8986(T) should be classified
      as a new species, namely Bordetella ansorpii sp. nov.

PMID- 15872301
TI  - In vitro activity of voriconazole against Prototheca wickerhamii: comparative
      evaluation of sensititre and NCCLS M27-A2 methods of detection.
AB  - A total of 104 Prototheca wickerhamii isolates and two control strains were
      tested for susceptibility to voriconazole using the Sensititre YeastOne
      colorimetric antifungal plate and NCCLS reference method. Voriconazole was highly
      active against all isolates, with an MIC at which 90% of isolates were inhibited
      of < or = 0.5 microg/ml. Comparison of MICs obtained with the Sensititre product
      and the NCCLS method demonstrated agreement (100% +/- 2 log2 dilutions) between
      the two methods. Voriconazole may offer an option for the treatment of Prototheca
      sp. infections, and its efficacy should be established through clinical
      experience.

PMID- 15872302
TI  - Methods for reducing bacterial contamination in the BacT/Alert mycobacterial
      culture detection system.
AB  - Two methods were compared for decreasing bacterial contamination in the
      BacT/Alert mycobacterial culture detection system. Two concentrations, 0.5 ml
      (standard amount) and 1.0 ml, of mycobacterial antibiotic supplement were
      evaluated. Contamination rates were 14% and 6% for the standard and the doubled
      concentrations, respectively. This difference was statistically significant (P <
      0.005).

PMID- 15872303
TI  - Rahnella aquatilis bacteremia from a suspected urinary source.
AB  - A 76-year-old male with prostatic hyperplasia presented with acute
      pyelonephritis. Blood cultures yielded Rahnella aquatilis. Treatment with
      intravenous followed by oral levofloxacin resulted in cure. Important
      characteristics of this organism include its biochemical similarities to
      Enterobacter agglomerans, its apparent ability to cause bacteremia from a renal
      focus, and its response to quinolone therapy.

PMID- 15872304
TI  - Bartonella species as a potential cause of epistaxis in dogs.
AB  - Infection with a Bartonella species was implicated in three cases of epistaxis in
      dogs, based upon isolation, serology, or PCR amplification. These cases, in
      conjunction with previously published reports, support a potential role for
      Bartonella spp. as a cause of epistaxis in dogs and potentially in other animals,
      including humans.

PMID- 15872305
TI  - Human cytomegalovirus infection of a severe-burn patient: evidence for productive
      self-limited viral replication in blood and lung.
AB  - To date, only seroepidemiological data are available on the role of human
      cytomegalovirus (HCMV) in patients with severe burns. We present the first
      longitudinal analysis of disseminated HCMV infection with a demonstration of self
      limited productive viral replication identified in both the blood and lung of a
      burn patient.

PMID- 15872307
TI  - Unusual laboratory findings in a case of Norwegian scabies provided a clue to
      diagnosis.
AB  - The diagnosis of Norwegian scabies was missed for a year for an elderly long-term
      care facility resident. Serpiginous tracks were noted on the surface of Sabouraud
      dextrose agar used for fungal culture of the skin scrapings. This unusual
      laboratory manifestation must alert clinical microbiologists to the possible
      diagnosis of scabies.

PMID- 15872306
TI  - Listeria-associated arthritis in a patient undergoing etanercept therapy: case
      report and review of the literature.
AB  - Listeriosis can be a cause of infectious arthritis. Here, we present a case of
      articular listeriosis in a patient with rheumatoid arthritis receiving treatment
      with etanercept, a tumor necrosis factor antagonist. We review the literature of
      articular listeriosis and discuss the role of tumor necrosis factor blockade in
      precipitating listeriosis.

PMID- 15872308
TI  - New quality control strain for use in routine testing for production of extended
      spectrum Beta-lactamases by enterobacteriaceae.

PMID- 15872309
TI  - Chlamydia trachomatis serovars causing urogenital infections in women in
      Melbourne, Australia.

PMID- 15872310
TI  - Good as new.

PMID- 15872311
TI  - Carnosine: a versatile antioxidant and antiglycating agent.
AB  - Carnosine (beta-alanyl-L-histidine) has recently attracted much attention as a
      naturally occurring antioxidant and transition-metal ion sequestering agent. It
      has also been shown to act as an anti-glycating agent, inhibiting the formation
      of advanced glycation end products (AGEs). Through its distinctive combination of
      antioxidant and antiglycating properties, carnosine is able to attenuate cellular
      oxidative stress and can inhibit the intracellular formation of reactive oxygen
      species and reactive nitrogen species. By controlling oxidative stress,
      suppressing glycation, and chelating metal ions, carnosine is able to reduce
      harmful sequelae such as DNA damage. AGEs are known contributors to the pathology
      of Alzheimer's disease, and carnosine therefore merits serious attention as a
      possible therapeutic agent.

PMID- 15872312
TI  - Nek8 mutation causes overexpression of galectin-1, sorcin, and vimentin and
      accumulation of the major urinary protein in renal cysts of jck mice.
AB  - The jck murine model, which results from a double point mutation in the nek8
      gene, has been used to study the mechanism of autosomal recessive polycystic
      kidney disease (ARPKD). The renal proteome of jck mice was characterized by two
      dimensional gel electrophoresis combined with mass spectrometry (MALDI-TOF/TOF).
      Four newly identified proteins were found to accumulate in the kidneys of jck
      mice with polycystic kidney disease (PKD) compared with their wild-type
      littermates. The proteins galectin-1, sorcin, and vimentin were found to be
      induced 9-, 9-, and 25-fold, respectively, in the PKD proteome relative to the
      wild type. The identity of these proteins was established by peptide mass
      fingerprinting and de novo MS/MS sequencing of selected peptides. Up-regulation
      of these three proteins may be due to the nek8 mutation, and their function may
      be related to the signaling and structural processes in the primary cilium.
      Additionally a series of protein isoforms observed only in the ARPKD kidney was
      identified as the major urinary protein (MUP). Peptide sequencing demonstrated
      that the isoforms MUP1, MUP2, and MUP6 are contained in this series. The MUP
      series showed a number of male-specific isoforms and a phosphorylation of the
      entire series with an increasing degree of phosphorylation of the acidic
      isoforms. In addition, the MUP series was localized to the cyst fluid of PKD
      mice, and a cellular mislocalization of galectin-1, sorcin, and vimentin in PKD
      tubular epithelial cells was shown. The abnormal and extremely high accumulation
      of the MUPs in the ARPKD kidney may be linked to a defect in protein transport
      and secretion. The discovery of these proteins will provide new information on
      the molecular and cellular processes associated with the mechanism of ARPKD.

PMID- 15872313
TI  - Quality improvement guidelines for percutaneous management of acute limb
      ischemia.

PMID- 15872314
TI  - Concepts, considerations, and concerns on the cutting edge of radiofrequency
      ablation.
AB  - Radiofrequency (RF) ablation is rapidly expanding from a tool to treat isolated
      hepatic malignancy to a therapy for patients with renal, adrenal, skeletal,
      breast, lung, and other soft-tissue neoplasms. The purpose of this article is to
      review the status of RF ablation outside the liver and lung and compare outcomes
      with current clinical standards when appropriate. The author also reviews how
      differences in local tissue environments play a role in creation of a thermal
      lesion and achievement of subsequent clinical success.

PMID- 15872315
TI  - American Association for the Study of Liver Diseases Practice Guidelines: the
      role of transjugular intrahepatic portosystemic shunt creation in the management
      of portal hypertension.

PMID- 15872316
TI  - SIR 2005 Annual Meeting Film Panel Case: traumatic pericallosal pseudoaneurysm.

PMID- 15872317
TI  - SIR 2005 Annual Meeting Film Panel Case: hemoptysis and bronchial artery
      embolization in an adult with uncorrected truncus arteriosus and Eisenmenger
      syndrome.

PMID- 15872318
TI  - SIR 2005 Annual Meeting Film Panel Case: mucoepidermoid carcinoma.

PMID- 15872319
TI  - SIR 2005 Annual Meeting Film Panel Case: vascular type Ehlers-Danlos syndrome.

PMID- 15872320
TI  - Transcatheter thrombolytic therapy for acute mesenteric and portal vein
      thrombosis.
AB  - PURPOSE: The purpose of this study was to evaluate the utility of transcatheter
      thrombolytic therapy in 20 patients with acute or subacute (symptoms <40 days)
      portal and/or mesenteric vein thrombosis with severe symptoms, deteriorating
      clinical condition, and/or persistent symptoms despite anticoagulation. MATERIALS
      AND METHODS: This retrospective study examined 12 male patients and eight female
      patients seen over a period of 11 years. The average age was 37.6 years. Four of
      the patients had previously undergone liver transplantation. An anatomic
      classification system was established to describe the extent of thrombus at the
      time of diagnosis. Patients were treated with thrombolytic therapy via the
      transhepatic route, common femoral vein route, and/or superior mesenteric artery
      route. Improvement in symptoms, avoidance of bowel resection, complications, and
      radiographic evidence of clot resolution were the main clinical outcomes.
      RESULTS: Fifteen of the 20 patients exhibited some degree of lysis of the
      thrombus. Three patients had complete resolution, 12 had partial resolution, and
      five had no resolution. Eighty-five percent of patients (n = 17) had resolution
      of symptoms. Sixty percent of patients (n = 12) developed a major complication.
      No patients required bowel resection after thrombolytic therapy. One patient died
      with gastrointestinal hemorrhage and septic shock 2 weeks after thrombolytic
      therapy. Other major complications included bleeding and conditions requiring
      transfusion. No patients developed new portal or mesenteric thromboses. Two of
      the patients who received transplants eventually required repeat transplantation.
      CONCLUSIONS: Transcatheter thrombolysis was beneficial in avoiding patient death,
      resolving thrombus, improving symptoms, and avoiding bowel resection. However,
      there was a high complication rate, indicating that this therapy should be
      reserved for patients with severe disease. Further evaluation of these techniques
      and outcomes should continue to be pursued.

PMID- 15872321
TI  - Use of CT angiography to classify endoleaks after endovascular repair of
      abdominal aortic aneurysms.
AB  - PURPOSE: Accurate endoleak detection and classification is critical for the
      follow-up of patients who have undergone endovascular aneurysm repair (EVAR).
      This determination is often made with computed tomography angiography (CTA). This
      investigation was performed to determine the accuracy of CTA in the
      classification of endoleaks in patients who have undergone EVAR. MATERIALS AND
      METHODS: Thirty-six patients with endoleaks underwent both CTA and conventional
      contrast digital subtraction angiography (DSA) to determine endoleak etiology.
      Two independent radiologists determined the source of the endoleak based on a
      retrospective review of the CTA. The results of the CTA-based endoleak
      classification were compared to the reference standard, contrast DSA. RESULTS:
      There was agreement regarding endoleak classification between CTA and DSA on 86%
      of the patients (31 of 36 patients). Correlation between the CTA reading of the
      two readers was 94% (34 of 36 patients), yielding a kappa statistic of 0.8. In
      three patients, the CTA reading incorrectly classified endoleaks as type 2 when
      the endoleaks were actually type 1 endoleaks on DSA. One patient was incorrectly
      classified as having a type 1 endoleak on CTA when it was a type 2 endoleak on
      DSA. Finally, one patient had a type 1 endoleak on DSA that was incorrectly
      classified as a type 3 endoleak on CTA. The change in CTA endoleak classification
      based on the DSA resulted in a significant change in patient management in four
      of the 36 patients (11%). CONCLUSIONS: Endoleak classification based on CTA
      correlates fairly well with DSA findings. However, optimal endoleak management
      requires performance of selective angiograms with DSA to classify endoleaks that
      are detected on CTA.

PMID- 15872322
TI  - In vivo evaluation of the carotid wallstent on three-dimensional contrast
      material-enhanced MR angiography: influence of artifacts on the visibility of
      stent lumina.
AB  - PURPOSE: Contrast material-enhanced magnetic resonance (MR) angiography is
      increasingly used in postinterventional imaging after implantation of
      endovascular stents. The main limitations are stent-related artifacts
      compromising the visibility of the stent lumen. The aim of this in vivo study is
      the evaluation of contrast-enhanced MR angiography imaging characteristics of the
      carotid Wallstent. MATERIALS AND METHODS: The carotid arteries of 29 patients
      were examined with contrast-enhanced MR angiography 3-6 days and/or 7-23 months
      after implantation of a carotid Wallstent into the internal carotid artery.
      Images were evaluated with regard to the diameter and signal intensity (SI) of
      the visible stent lumen. Digital subtraction angiography (DSA) was used as the
      standard of reference. RESULTS: Stent-related artifacts on contrast-enhanced MR
      angiography caused an artificial lumen narrowing and a reduction of the SI within
      the stent. Artifacts were pronounced on imaging 3-6 days after stent
      implantation, but 68% of stents imaged 7-23 months after stent implantation
      presented with a significantly decreased artificial signal reduction and an
      improved visibility of the stent lumen. CONCLUSIONS: The results of this study
      indicate that a reliable evaluation of the stent lumen is limited as a result of
      an artificial decrease of the SI inside the stent. However, in follow-up
      examinations 7-23 months after stent implantation, visibility of the stent lumen
      was improved and diagnostic reliability of contrast-enhanced MR angiography was
      markedly increased. A probable explanation for this phenomenon might be the
      formation of a neointimal layer covering the stent struts and thereby reducing
      stent-related artifacts.

PMID- 15872323
TI  - Percutaneous radiofrequency ablation of renal tumors: technique, complications,
      and outcomes.
AB  - PURPOSE: To report the safety, technical success, and effectiveness of
      percutaneous radiofrequency (RF) ablation for renal tumors. MATERIALS AND
      METHODS: The authors retrospectively reviewed the medical records and imaging
      studies of 29 consecutive patients (18 men, 11 women; mean age, 65 +/- 2.62
      years) with 30 renal tumors (mean diameter, 3.5 +/- 0.24 cm) who underwent
      percutaneous RF ablation at their institution from September 2001 to March 2004.
      All procedures were performed with computed tomography guidance with general
      anesthesia, and all patients were admitted to the hospital for overnight
      observation. Technical success, complications, and their management were
      recorded. Technique effectiveness was assessed by imaging and clinical follow up.
      RESULTS: Overall, 88 overlapping ablations were performed (mean, 2.6 +/- 0.16
      ablations per tumor per session) in 34 sessions. There were four major
      complications (12%). Three patients had gross hematuria and urinary obstruction,
      all were successfully treated. One patient had persistent anterior abdominal wall
      weakness. There were also two minor complications (6%) without significant
      clinical sequelae. One patient had gross hematuria which resolved spontaneously,
      another patient had transient paresthesia of the anterior abdominal wall. There
      were no significant changes in renal function after RF ablation. The intent of RF
      ablation was eradication of the primary tumor in 27 patients and treatment of
      gross hematuria in the other two. Technical success was achieved in all cases.
      Follow-up images were available for 26 patients. The primary tumor was completely
      ablated in 23 of 24 patients (96%) in whom eradication of the primary tumor was
      attempted (follow up period: mean, 10 months, median 7 months). The two patients
      treated for hematuria remained asymptomatic for 6 and 27 months each. CONCLUSION:
      Percutaneous RF ablation for renal tumors is safe and well tolerated. High
      technical success rates are expected. Early reports of the technique's
      effectiveness are promising.

PMID- 15872324
TI  - Spinal CT-guided interventional procedures for management of chronic back pain.
AB  - PURPOSE: Image-guided interventional procedures have arisen as an alternative for
      management of back pain, with controversial indications and efficacy. This study
      describes the technique, clinical impact, and complications of computed
      tomography (CT)-guided infiltrations for the management of chronic back pain.
      MATERIALS AND METHODS: One hundred eleven patients with chronic back pain treated
      with CT-guided infiltrations were studied prospectively. Procedures performed
      included nerve root, facet joint, epidural, and sacroiliac joint blocks. Pain
      intensity was evaluated with use of a visual analog scale. RESULTS: Two hundred
      twenty-two infiltrations were performed in 111 consecutive patients. After 18
      months of follow-up, pain improvement lasted for a mean duration of 9 months and
      the complication rate was less than 1%. Moderate to good pain response was seen
      in 95% of followed patients and 4% of patients required surgery. CONCLUSION:
      Spinal CT-guided infiltration constitutes an effective therapy for chronic back
      pain. This series confirms a low complication rate, good response, and high
      therapeutic value.

PMID- 15872325
TI  - Gastric outlet obstruction caused by benign anastomotic stricture: treatment by
      fluoroscopically guided balloon dilation.
AB  - PURPOSE: To evaluate the clinical efficacy and safety of fluoroscopically guided
      balloon dilation of gastric outlet obstruction caused by benign anastomotic
      stricture. MATERIALS AND METHODS: Fluoroscopically guided balloon dilation was
      performed on 17 patients with gastric outlet obstruction caused by benign
      anastomotic stricture. Fourteen patients underwent surgery for malignant disease
      and three patients for complication of benign gastric ulcer. The sites of
      anastomotic stricture were gastrojejunal (n = 12) or gastroduodenal (n = 5). An
      upper gastrointestinal (UGI) series was performed just following and 1 month
      after balloon dilation to evaluate both the clinical success of the procedure and
      any complications. A dietary intake was evaluated by using the score for patients
      with malignant dysphagia and the pre- and postballoon dilation scores were
      analyzed with the Wilcoxon signed rank test. RESULTS: In all patients,
      fluoroscopically guided balloon dilation was performed in one (n = 15) or two (n
      = 2) sessions and was technically and clinically successful (100%). The diameters
      of the balloon catheters used were 15 mm (n = 4), 20 mm (n = 14), and 25 mm (n =
      1 mm; mean, 19.5 mm) in a total of 19 sessions. All patients had significant
      improvement of their levels of dietary intake (P < .001). Two of the 17 patients
      required the second procedure due to recurrent symptom nine and 15 months,
      respectively, after initial balloon dilation. Overall, 16 patients (94%) showed
      good results and no recurrence during a mean follow-up period of 13.5 months
      (range, 5-39 months). There were no major complications associated with balloon
      dilation. CONCLUSION: Fluoroscopically guided balloon dilation seems to be
      effective and safe for patients with gastric outlet obstruction caused by benign
      anastomotic stricture. Achieving a luminal diameter of 20 mm seems to be
      necessary to prevent recurrence of symptoms.

PMID- 15872326
TI  - Effects of a holmium-166 incorporated covered stent placement in normal canine
      common bile ducts.
AB  - PURPOSE: A specially designed self-expandable covered metallic stent incorporated
      with beta-emitting radioisotope, Holmium-166 (Ho-166), was developed for
      delivering intraluminal brachytherapy as well as for internal bile drainage in
      malignant biliary stricture. The purpose of the study was to demonstrate the
      safety and tissue response of the radioactive metallic stent on the normal canine
      common bile duct (CBD) prior to the clinical application. MATERIALS AND METHODS:
      Nitinol self-expandable stents (diameter; 4 mm, length; 20 mm) were covered with
      polyurethane membrane (50 microm thick) containing 21 to 135 muCi of Ho-166
      (mean, 77.9 microCi). To prevent migration of stent, the membrane covered only
      the middle 1 cm of the stent and the ends of the stent were left uncovered. The
      stents were placed in the CBD of 20 healthy beagle dogs. For control, non
      radioactive covered stents were placed in another three dogs. The dogs were
      killed 3 to 6 months after stent insertion and histopathologic examination of CBD
      was performed. RESULTS: There was no stent migration in all cases. Varying
      degrees of papillary mucosal hyperplasia leading to significant narrowing of the
      lumen was observed within the lumen of the bare portion and under the mucosal
      surface of the non-radioactive covered stents. However, fibrosis was noted in Ho
      166 coated area, instead of mucosal hyperplasia. Severity of fibrosis was
      correlated with estimated radiation dose. Despite high dose, there was no
      perforation of CBD wall. The membrane of Ho-166 coat was disrupted in some cases
      of 6 months follow-up. CONCLUSIONS: Holmium-166 incorporated covered stents
      demonstrated fibrosis of CBD wall and inhibition of ingrowth of mucosal
      hyperplasia without serious complication such as perforation, while control group
      showed severe mucosal hyperplasia.

PMID- 15872327
TI  - Adverse cerebrovascular effects of intraarterial CO2 injections: development of
      an in vitro/in vivo model for assessment of gas-based toxicity.
AB  - PURPOSE: To assess whether and how CO(2) can cause ischemic injury in the central
      nervous system after internal carotid artery injection. MATERIALS AND METHODS: In
      14 adult pigs, both internal carotid arteries were catheterized via a
      transfemoral approach. One carotid artery served as control and the other was
      injected via a prototype gas injector with defined volumes and pressures of gas.
      Effects were assessed by clinical observation, repeated magnetic resonance (MR)
      imaging, histopathology, and vital staining. An in vitro flow circuit was used to
      model injection parameters. RESULTS: Single injections of CO(2) did not produce
      persistent clinical symptomatology. In vitro conditions were created in which
      bubbles adhered to the tubing of the circuit, creating functional stenoses, or
      coalesced into larger bubbles that became trapped, thereby reducing flow and
      augmenting potential embologenic effects of subsequent injections. With in vitro
      derived dual injection parameters, seven pigs underwent two sequential injections
      of CO(2). All did well after the first injections, but all had adverse effects
      after the second injections, including involuntary tonic-clonic muscular
      movements, cardiopulmonary arrest, recurrent intractable seizure activity during
      recovery, hemorrhagic venous infarcts on gross and histopathologic examination,
      and blood-brain barrier breakdown on vital staining. MR imaging was not sensitive
      even after symptomatic intraarterial air injection. CONCLUSIONS: Absence of
      adverse effects after single bolus injections in pigs does not prove the safety
      of intracranial CO(2) injections in human patients. Considering the possible
      deleterious effects of repeat intravascular injections in the highly sensitive
      system of the brain, it may be prudent for clinical application at other approved
      sites to let time pass between boluses sufficient to permit absorption of wall
      adherent and coalescent bubbles that could cause gas embolic events.

PMID- 15872328
TI  - SVC syndrome with a patent SVC: treatment of internal jugular venous occlusion
      after surgical and radiation therapy of esophageal cancer.
AB  - A patient is described in whom recanalization and stent placement in an occluded
      internal jugular vein was performed for the treatment of refractory facial edema
      initially thought to be lymphedema. The authors describe the combination of
      venous obstructions leading to this clinical presentation, which they term "SVC
      syndrome with a patent SVC."

PMID- 15872329
TI  - IVC stent deployment via translumbar approach.
AB  - Percutaneous translumbar access was used for angioplasty and stent deployment in
      the suprarenal inferior vena cava (IVC). The patient, who was undergoing
      hemodialysis via a translumbar tunneled hemodialysis catheter, was found to have
      near-total occlusion of the suprarenal IVC. Following treatment, subsequent
      improvement of flow was present in the IVC and hemodialysis catheter.

PMID- 15872330
TI  - Endovascular repair of inflammatory abdominal aneurysm: a retrospective analysis
      of CT follow-up.
AB  - Retrospective radiologic and clinical midterm follow-up is reported for 10
      patients with inflammatory abdominal aortic aneurysm (IAAA) after endovascular
      aortic aneurysm repair (EVAR). At a mean follow-up of 33 months, regression of
      the thickness of the perianeurysmal fibrosis (PAF) and decrease of aneurysmal sac
      diameter was observed in nine patients. Four EVAR-associated complications were
      observed: periinterventional dissection of femoral artery (n = 1), blue toe
      syndrome (n = 1), and stent-graft disconnection (n = 2). EVAR is the less
      invasive method of aneurysm exclusion in patients with IAAA with a comparable
      evolution of the PAF as reported after open repair.

PMID- 15872331
TI  - Radiofrequency ablation of needle tract seeding in hepatocellular carcinoma.
AB  - A tumor needle tract seeding, 20 mm in diameter, was detected with magnetic
      resonance (MR) imaging in a 72-year-old man, 10 months after radiofrequency
      ablation of a 55-mm subcapsular hepatocellular carcinoma. This seeding was
      successfully treated with ultrasound-guided percutaneous radiofrequency ablation.
      No recurrence was found after a 2-year follow-up either on contrast-enhanced
      computed tomography or MR imaging. Needle tract seeding treatment is not well
      established. Percutaneous radiofrequency ablation of such seeding is one elegant
      potential treatment option. Efficacy seems promising but has to be confirmed in
      larger series. Further evaluation is needed.

PMID- 15872332
TI  - Radiofrequency ablation for treatment of symptomatic low-flow vascular
      malformations after previous unsuccessful therapy.
AB  - Three patients with low-flow soft-tissue vascular malformations were treated with
      radiofrequency (RF) ablation. Other treatment options had proven unsuccessful.
      After RF ablation treatment, two patients were free of symptoms and one reported
      decreased symptoms followed by a return of symptoms within 1 year. No procedure
      related complications occurred. It is suggested that RF ablation may be offered
      as an alternative treatment option for symptomatic vascular malformations when
      others have failed or are not possible.

PMID- 15872333
TI  - Torulopsis glabrata fungemia from infected transjugular intrahepatic
      portosystemic shunt stent.
AB  - Transjugular intrahepatic portosystemic shunts (TIPS) are used to manage multiple
      complications of portal hypertension. Accounts of infection of TIPS stents are
      uncommon. The literature reports two cases of TIPS-associated Torulopsis glabrata
      (Candida glabrata) fungemia; both patients died within a year of TIPS placement
      despite therapy with intravenous antifungal agents. This report describes the
      successful long-term survival of a patient with Torulopsis TIPS stent infection.

PMID- 15872334
TI  - Intraperitoneal saline infusion during radiofrequency ablation of subcapsular
      hepatic tumor.

PMID- 15872335
TI  - Dynamics of diabetes-associated autoantibodies in young children with human
      leukocyte antigen-conferred risk of type 1 diabetes recruited from the general
      population.
AB  - This study characterized the dynamics of islet cell antibodies (ICA), insulin
      antibodies (IAA), glutamic acid decarboxylase antibodies (GADA), and IA-2
      antibodies (IA-2A) in 1006 children recruited from the general population due to
      human leukocyte antigen (HLA) DQB1-conferred risk for type 1 diabetes (T1D). By
      the age of 5 yr, 13.8% of the children had had one or more autoantibodies in at
      least one sample drawn at 3- to 12-month intervals from birth, whereas 6.1% had
      had one or more of the three autoantibodies to biochemically defined antigens in
      at least two consecutive samples. The cumulative frequencies of positivity for at
      least two antibodies ranged from 3.2-4.4%. Seventy-five children (7.5%) had at
      least once ICA, 83 (8.3%) had IAA, 46 (4.6%) had GADA, and 33 (3.3%) had IA-2A.
      IAA were transient more frequently than the other antibodies (P < or = 0.03) and
      fluctuated between positivity and negativity more often than ICA (P = 0.001). The
      genetically high risk children were positive for each autoantibody reactivity
      more often (P < or = 0.03) than the moderate risk subjects. Thirteen of the 1006
      children (1.3%) presented with T1D by the age of 5 yr. The most sensitive
      predictors of T1D were ICA and IAA, whereas the most specific predictor was IA
      2A. Positivity for at least two autoantibodies of IAA, GADA, and IA-2A had the
      highest positive predictive value for T1D (34%). We conclude that the frequency
      of various diabetes-associated autoantibodies increases at a relatively stable
      rate at least up to the age of 5 yr. Persistent positivity for two or more
      autoantibodies appears to reflect destructive progressive beta-cell autoimmunity,
      whereas positivity for a single autoantibody may represent harmless
      nonprogressive or even regressive beta-cell autoimmunity.

PMID- 15872336
TI  - Estrogen replacement therapy increases plasma ghrelin levels.
AB  - Ghrelin is a novel peptide hormone that has GH releasing activity and also other
      endocrine and metabolic functions. The purpose of this study was to investigate
      the effects of estrogen replacement therapy on plasma active ghrelin levels in 64
      hysterectomized postmenopausal women receiving peroral estrogen (PE) or
      transdermal estrogen therapy for 6 months. Active ghrelin was measured using
      commercial RIA. Estrogen therapy increased plasma active ghrelin from 479 +/- 118
      to 521 +/- 123 pg/ml (P = 0.002) among all the study subjects. PE therapy
      increased plasma ghrelin levels from 465 +/- 99 to 536 +/- 104 pg/ml (P = 0.001).
      Transdermal estrogen therapy did not increase plasma ghrelin levels significantly
      (from 491 +/- 132 to 509 +/- 138 pg/ml; P = 0.332). The relative changes in
      plasma ghrelin levels were associated with the relative changes in serum
      estradiol concentrations (r = 0.299; P = 0.017). During the estrogen therapy,
      negative associations were found between plasma active ghrelin levels and several
      plasma lipids (total cholesterol, low-density lipoprotein cholesterol, very low
      density lipoprotein cholesterol, total triglycerides, and very low-density
      lipoprotein triglycerides). As a conclusion, estrogen replacement therapy
      increased active plasma ghrelin levels, particularly PE therapy. Additional
      studies are needed to determine the possible underlying mechanisms.

PMID- 15872337
TI  - Image in endocrinology: adrenal pseudocyst.

PMID- 15872338
TI  - 25-OH-vitamin D assays.

PMID- 15872339
TI  - Monocyte chemoattractant protein-1 in adipose tissue.

PMID- 15872340
TI  - 25-OH-vitamin D assays.

PMID- 15872341
TI  - Leukocyte receptor-binding radiopharmaceuticals for infection and inflammation
      scintigraphy.

PMID- 15872342
TI  - Gated SPECT evaluation of outcome after abciximab-supported primary infarct
      artery stenting for acute myocardial infarction: the scintigraphic data of the
      abciximab and carbostent evaluation (ACE) randomized trial.
AB  - We used gated SPECT to evaluate the impact of abciximab on the efficacy of
      myocardial reperfusion in patients with acute myocardial infarction undergoing
      infarct-related artery stenting. METHODS: The Abciximab and Carbostent Evaluation
      (ACE) trial randomized 400 infarct patients to stenting alone or stenting plus
      abciximab. One-month (99m)Tc-sestamibi gated SPECT was planned in a subgroup of
      consecutive patients to evaluate infarct size, infarct severity, left ventricular
      volumes, and ejection fraction. RESULTS: The final study population included 182
      patients (99 randomized to abciximab and 83 to stenting alone). Gated SPECT
      revealed smaller infarcts in the abciximab group than in the stenting-alone group
      (14.3% +/- 11.7% vs. 18.1% +/- 13%, P < 0.02), and lower infarct severity
      (minimum-to-maximum count ratio = 0.47 +/- 0.17 vs. 0.41 +/- 0.15, P < 0.02),
      resulting in a smaller left ventricular end-diastolic volume index (57.8 +/- 20.0
      vs. 64.6 +/- 20.8 mL/m(2), P = 0.03) and left ventricular end-systolic volume
      index (31.7 +/- 17.4 vs. 37.5 +/- 18.6 mL/m(2), P = 0.05) in the abciximab group.
      One-month left ventricular ejection fraction was significantly higher in patients
      randomized to abciximab (47.4% +/- 11.3% vs. 43.9% +/- 11.7%, P = 0.05).
      CONCLUSION: The use of abciximab therapy as an adjunct to infarct-related artery
      stenting leads to a reduction in infarct size and severity, resulting in smaller
      1-mo left ventricular volumes and better left ventricular function. Gated SPECT
      appears to be an ideal tool for outcome assessment in infarct patients undergoing
      different treatment strategies.

PMID- 15872343
TI  - Automatic detection and size quantification of infarcts by myocardial perfusion
      SPECT: clinical validation by delayed-enhancement MRI.
AB  - We aimed to validate the accuracy of a new automated myocardial perfusion SPECT
      quantification based on normal limits for detection and sizing of infarcts, using
      delayed-enhancement MRI (DE-MRI) as a gold standard. METHODS: Eighty-two
      immediate (201)Tl rest scans and 26 (201)Tl delayed redistribution scans were
      compared with resting DE-MRI scans acquired within 24 h of SPECT acquisition. The
      immediate (201)Tl scans were considered for validation of infarct detection and
      the delayed (201)Tl scans were considered for infarct sizing. A simplified
      quantification scheme was used in which defect extent (EXT) and total perfusion
      deficit (TPD) parameters were derived automatically from SPECT images by
      comparison with sex-matched normal limits and applying a 3.0 average deviation
      criterion. The total extent of hyperenhancement expressed as the percentage of
      the left ventricle was derived from DE-MRI images by visual definition of
      myocardial contours and defects. DE-MRI and SPECT images were fused in 3
      dimensions for visual comparison. Phantom data were also quantified using the
      same EXT and TPD measures for defects ranging from 5% to 70% of the myocardium.
      RESULTS: The area under the receiver-operator-characteristic curve for the
      detection of infarct on immediate rest scans was 0.91 +/- 0.03 for EXT and 0.90
      +/- 0.03 for TPD (P = not significant). The sensitivity and specificity for the
      detection of infarct by EXT on immediate (201)Tl rest scan were 87% and 91%,
      respectively, with the optimal defect size threshold of 4%. Six of 7 cases with
      DE-MRI defects < 5% were detected by SPECT. Infarct sizes obtained from DE-MRI
      correlated well with EXT (slope = 0.94, offset = 3.8%; r = 0.84) and TPD (slope =
      0.75, offset = 4.2%; r = 0.85) obtained from delayed SPECT (201)Tl scans.
      Excellent correlation was observed between the SPECT quantification and the
      physical defect size for the phantom data. The actual size of the defect was
      better estimated by EXT (slope = 1.00, offset 1.33%; r = 0.99) than by TPD (slope
      = 0.79, offset = 1.9%; r = 0.99). CONCLUSION: Automated quantification of the EXT
      on myocardial perfusion SPECT images can reliably detect infarcts and measure
      infarct sizes.

PMID- 15872344
TI  - Attenuation correction of myocardial SPECT perfusion images with low-dose CT:
      evaluation of the method by comparison with perfusion PET.
AB  - In cardiac SPECT, specificity is significantly affected by artifacts due to
      photon absorption. As the success of attenuation correction depends mainly on
      high-quality attenuation maps, SPECT low-dose CT devices are promising. We wanted
      to evaluate the usefulness of a SPECT low-dose CT device in myocardial perfusion
      scintigraphy. For the evaluation of attenuation correction systems, primarily
      comparisons with coronary angiography are used. Because the comparison of a
      method showing myocardial perfusion with an investigation displaying the
      morphology of vessels yields some difficulties, we chose perfusion PET with (13)N
      ammonia as the reference method. METHODS: We prospectively analyzed 23 patients
      (6 women, 17 men) with known or suspected coronary artery disease. Rest studies
      and studies under pharmacologic stress with adenosine were performed. After
      simultaneous injection of (13)N-ammonia and (99m)Tc-sestamibi, a dynamic PET
      acquisition was started. The SPECT study was performed about 2 h later. Based on
      20-segment polar maps, SPECT with and without attenuation correction was compared
      with PET-derived perfusion values and ammonia uptake values. The PET uptake
      images were also smoothed to adjust their resolution to the resolution of the
      SPECT images. RESULTS: The concordance of SPECT and PET studies was improved
      after attenuation correction. The main effect was seen in the inferior wall.
      Especially in the apex and anterolateral wall, there were differences between
      SPECT and PET studies not attributable to attenuation artifacts. Because these
      differences diminished after smoothing of the PET studies, they might be due to
      partial-volume effects caused by the inferior resolution of the SPECT images.
      CONCLUSION: The x-ray-derived attenuation correction leads to SPECT images that
      represent myocardial perfusion more accurately than nonattenuation-corrected
      SPECT images. The benefit of the method is seen primarily in the inferior wall.
      The low resolution of the SPECT system may lead to artifacts due to partial
      volume effects. This phenomenon must be considered when perfusion PET is used as
      a reference method to investigate the effect of attenuation correction.

PMID- 15872346
TI  - Detection of unexpected additional primary malignancies with PET/CT.
AB  - This study evaluated the yield of whole-body (18)F-FDG PET/CT for the detection
      of unexpected (18)F-FDG-avid additional primary malignant tumors in patients
      being evaluated by PET/CT for known or suspected malignances. METHODS: Reports
      from whole-body (18)F-FDG PET/CT scans from June 2001 to June 2003 were reviewed,
      and 1,912 patients (924 men and 988 women; mean age +/- SD, 58.9 +/- 13.9 y) who
      had been scanned for known or suspected malignant lesions were included in this
      study. The sites of known or suspected primary tumors included lung (28.6%),
      colon or rectum (12.4%), head or neck (12.1%), lymph nodes (10.9%), breast
      (7.6%), gynecologic organs (7.1%), genitourinary organs (4.2%), esophagus (3.6%),
      skin (melanoma) (3.5%), pancreas (2.5%), bone or soft tissue (2.2%), and other
      sites (5.4%). Lesions that were newly discovered on PET/CT, had not been
      previously detected by other modalities, and were atypical in location for
      metastases on the PET/CT study were interpreted as suggestive of a new primary
      malignant tumor. These abnormalities were compared with the final diagnosis
      obtained from the medical records, including pathologic reports. RESULTS: PET
      positive lesions suggestive of new primary malignant tumors were found in 79
      (4.1%) of 1,912 patients. In 22 (1.2%) of 1,912 patients, these lesions were
      pathologically proven to be malignant. Proven sites were lung (7 lesions),
      thyroid (6 lesions), colon (4 lesions), breast (2 lesions), esophagus (2
      lesions), bile duct (1 lesion), and head and neck other than thyroid (1 lesion).
      Two new lesions in the lung and the thyroid were proven malignant in 1 patient.
      In 17 patients, the treatment plan was changed and the new lesion was surgically
      resected after the PET/CT examination. In 10 patients, PET was falsely positive
      after pathologic assessment. False-positive sites included thyroid (5 lesions),
      uterus (2 lesions), head and neck other than thyroid (2 lesions), and lung (1
      lesion). In 8 patients, the PET-positive lesions were considered benign after
      clinical follow-up of at least 8 mo. In 39 patients, the follow-up record was not
      yet available and the final diagnosis of the detected lesion has not yet been
      resolved. CONCLUSION: Whole-body PET/CT detected new, unexpected (18)F-FDG-avid
      primary malignant tumors in at least 1.2% of patients with cancer.

PMID- 15872345
TI  - Increased dopamine transporter availability associated with the 9-repeat allele
      of the SLC6A3 gene.
AB  - A polymorphism involving a variable number of tandem repeats (VNTR) has been
      described in the 3' untranslated region of the gene (SLC6A3) coding for the
      dopamine transporter (DAT). This polymorphism has 2 common alleles, designated as
      10-repeat (*10R) and 9-repeat (*9R), that have been linked with several human
      clinical phenotypes. Previous investigations of the effects of the SLC6A3
      polymorphism on DAT availability in smaller samples of humans have yielded
      divergent results. METHODS: We assessed genotype at the SLC6A3 promoter VNTR
      polymorphism in 96 healthy European Americans (age range, 18-88 y) who also
      underwent SPECT with (123)I-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (beta
      CIT) for measurement of striatal DAT protein availability. A ratio of specific to
      nondisplaceable brain uptake (i.e., V(3)'' = [striatal -occipital]/occipital), a
      measure proportional to the binding potential, was derived. For this analysis, 9
      9 homozygotes and 9-10 heterozygotes were grouped as SLC6A3 *9R carriers and
      contrasted with SLC6A3 *10R homozygotes. RESULTS: The SLC6A3 *9R carriers had
      significantly higher striatal DAT availability (V(3)'') than did the SLC6A3 *10R
      homozygotes, controlling for age (F(1,93) = 6.25, P = 0.014, analysis of
      covariance). The *9R carriers (n = 41, 49.8 +/- 19.5 y) had a mean increase in
      striatal DAT availability of 8.9% relative to the *10R homozygotes (n = 53, 49.9
      +/- 19.2 y). Striatal subregion analysis revealed that the effect of DAT genotype
      was significant for both the caudate and the putamen. CONCLUSION: These results
      support the interpretation of higher DAT levels in association with the *9R
      allele in European Americans and may relate to previously observed associations
      between DAT genotype and neuropsychiatric diseases.

PMID- 15872347
TI  - PET/CT detection of unexpected gastrointestinal foci of 18F-FDG uptake:
      incidence, localization patterns, and clinical significance.
AB  - Precise PET/CT localization of focal (18)F-FDG uptake in the gastrointestinal
      tract (GIT) may exclude malignancy in sites of physiologic activity but may also
      induce false-negative reports for malignant or premalignant lesions. The purpose
      of the present study was to retrospectively evaluate the nature and significance
      of unexpected focal (18)F-FDG uptake localized by PET/CT within the GIT. METHODS:
      The files of 4,390 patients referred for (18)F-FDG PET/CT were retrospectively
      reviewed. The incidence of studies showing unexpected focal uptake of (18)F-FDG
      localized by PET/CT to the GIT was determined. The position of these foci along
      the GIT and their intensity were recorded. The etiology of the findings was
      confirmed histologically or by long-term follow-up. RESULTS: Unexpected focal
      (18)F-FDG uptake in the GIT was found in 58 patients (1.3%). Follow-up data were
      available for 34 of these patients, including 4 with sites in the stomach, 2 in
      the small bowel, and 28 in the colon. GIT-related disease was confirmed in 24
      patients (71%). There were 11 malignant tumors, 9 premalignant lesions, and 4
      benign processes including 2 benign polyps, 1 case of active gastritis, and 1
      abscess of the sigmoid. Ten patients (29%) had no further evidence of GIT
      abnormality, and the suggestive sites were considered to be physiologic uptake.
      Maximal standardized uptake value was 17.3 +/- 10.2 in malignant lesions, 14.0 +/
      10.5 in premalignant lesions, 18.0 +/- 12.1 in benign lesions, and 11.1 +/- 7.4
      in foci of physiologic (18)F-FDG uptake in the GIT, with no statistically
      significant difference among the 4 subgroups. CONCLUSION: Incidental focal (18)F
      FDG uptake localized by PET/CT within the GIT is of clinical significance in most
      patients. These findings should be followed up with appropriate invasive
      procedures guided by hybrid imaging results.

PMID- 15872348
TI  - Characterization of 68Ga-DOTA-D-Phe1-Tyr3-octreotide kinetics in patients with
      meningiomas.
AB  - Because biopsy has a high risk of hemorrhage and the findings of CT and MRI are
      often ambiguous, especially at the base of the skull, additional methods for the
      characterization of intracranial tumors are needed. Meningiomas show high
      expression of the somatostatin receptor subtype 2 and thus offer the possibility
      of receptor-targeted imaging. We used the somatostatin analog (68)Ga-DOTA-d
      Phe(1)-Tyr(3)-octreotide (DOTA-TOC) labeled with the positron emitter (68)Ga
      (half-life, 68 min), obtained from a (68)Ge/(68)Ga generator, for PET of these
      tumors. In contrast to (18)F-FDG, this ligand shows high meningioma-to-background
      ratios. The aim was to evaluate kinetic parameters in meningiomas before
      radiotherapy. METHODS: Dynamic PET scans (3-dimensional mode; 28 frames; ordered
      subsets expectation maximization reconstruction) were acquired for 21 patients
      (mean age +/- SD, 51 +/- 13 y) before radiotherapy during the 60 min after
      intravenous injection of 156 +/- 29 MBq of (68)Ga-DOTA-TOC. We analyzed 28
      meningiomas (median grade [I] according to the system of the World Health
      Organization) with volumes of at least 0.5 mL (mean volume, 13.1 mL) and nasal
      mucosa as reference tissue, showing a slight to moderate physiologic uptake. For
      evaluation of the (68)Ga-DOTA-TOC kinetics, the vascular fraction (vB) and the
      rate constants (k1, k2, k3, and k4 [1/min]) were computed using a 2-tissue
      compartment model. Furthermore, receptor binding (RB) (k1 - k1 x k2) and the
      ratios k1/k2 and k3/k4 were calculated. RESULTS: Significant differences (P <
      0.05; t test) between meningiomas and the reference tissue were found for the
      mean standardized uptake value (10.5 vs.1.3), vB (0.42 vs. 0.11), k2 (0.12 vs.
      0.56), k3 (0.024 vs. 0.060), k4 (0.004 vs. 0.080), and RB (0.49 vs. 0.13).
      Although there was no significant difference for k1 (0.54 vs. 0.40), the ratios
      k1/k2 (4.50 vs. 0.71) and k3/k4 (6.00 vs. 0.75) were markedly greater in
      meningiomas than in reference tissue. CONCLUSION: The high uptake of (68)Ga-DOTA
      TOC in meningiomas can be explained by the high values for vB and by the
      remarkably low values for k2 and k4, leading to significantly greater k1/k2 and
      k3/k4 ratios and RB in meningiomas than in reference tissue. Thus,
      pharmacokinetic modeling offers a more detailed analysis of biologic properties
      of meningiomas. In further studies, these data might serve as a basis for
      monitoring the somatostatin receptors of meningiomas after radiotherapy.

PMID- 15872349
TI  - Whole-body 18F-FDG PET in recurrent or metastatic nasopharyngeal carcinoma.
AB  - The aim of this retrospective study was to evaluate the sensitivity and
      prognostic significance of whole-body (18)F-FDG PET for nasopharyngeal carcinoma
      (NPC) patients for whom there was a suspicion of recurrence or metastasis by
      conventional radiologic or clinical findings during their follow-up examinations.
      METHODS: Whole-body (18)F-FDG PET examinations were performed on 64 Taiwanese NPC
      patients (14 female, 50 male; mean age +/- SD, 45.8 +/- 13.0 y; age range, 16-75
      y) 4-70 mo (mean +/- SD, 14.1 +/- 13.5 mo) after radiotherapy or induction
      chemotherapy followed by concurrent chemoradiotherapy from February 1997 to May
      2001. The accuracy of (18)F-FDG PET detection for each patient was determined by
      the histopathologic results or other clinical evidence. RESULTS: The sensitivity,
      specificity, accuracy, positive predictive value, and negative predictive value
      of (18)F-FDG PET images in the diagnosis of NPC recurrence or metastases and
      secondary primary cancers were 92%, 90%, 92%, 90%, and 91%, respectively.
      Furthermore, the presence of (18)F-FDG hypermetabolism was highly correlated with
      the survival time of NPC patients. CONCLUSION: Whole-body (18)F-FDG PET is a
      sensitive follow-up diagnostic tool for the evaluation of NPC recurrences and
      metastases. It is also an effective prognostic indicator for NPC patients. To
      determine the optimized utilization of (18)F-FDG PET in the follow-up for NPC
      patients, further cost-effectiveness analysis of (18)F-FDG PET in combination
      with conventional management is necessary.

PMID- 15872350
TI  - Staging of untreated squamous cell carcinoma of buccal mucosa with 18F-FDG PET:
      comparison with head and neck CT/MRI and histopathology.
AB  - This prospective, nonrandomized, case-control study evaluated the impact of (18)F
      FDG PET in staging untreated squamous cell carcinoma of the buccal mucosa (BSCC)
      and compared the results with CT/MRI and histopathology. METHODS: Between January
      2002 and April 2004, 102 untreated BSCC patients with cM0 (no evidence of distant
      metastatic focus on chest radiograph, liver ultrasonograph, and bone scan) were
      enrolled with either conventional work-up (CWU, n = 51) or PET (CWU+PET, n = 51).
      All were monitored for at least 6 mo. The comparative diagnostic efficacies of
      PET and CT/MRI were evaluated using the area under the receiver-operating
      characteristic curve (AUC). The primary endpoint was the percentage reduction in
      futile surgery (preoperative detection of distant metastatic lesions). The
      secondary endpoint was the 2-y cumulative recurrence rate among study
      participants (with PET) compared with that of comparable control subjects
      (without PET). RESULTS: Significant benefits of PET compared with those of CT/MRI
      for BSCC patients were in the detection of locoregional (AUC, 0.973 vs. 0.928; P
      = 0.026), regional (AUC, 0.939 vs. 0.837; P = 0.026), and level II (AUC, 0.974
      vs. 0.717; P = 0.02) lymph nodes. Two percent (1/51) of the patients experienced
      a reduction in futile surgery in the CWU+PET group compared with 0% (0/51) in the
      CWU group. However, no statistical difference was found in the 2-y locoregional
      control rate between the CWU and the CWU+PET groups. CONCLUSION: The role of
      (18)F-FDG PET for BSCC with cM0 is limited. Although PET is superior to CT/MRI in
      identifying cervical nodal metastases, it does not improve locoregional
      recurrence.

PMID- 15872351
TI  - Identification of a new prostate-specific cyclic peptide with the bacterial
      FliTrx system.
AB  - Peptides are useful tools for directing radioisotopes into tumors. We evaluated
      the ability of a bacterial peptide display system to isolate new prostate tumor
      specific peptides. METHODS: We used the bacterial FliTrx system to identify a new
      cyclic peptide that binds to prostate carcinoma. Serum stability and binding
      affinities of the (125)I-labeled peptide were tested. Furthermore, the (131)I
      labeled peptide was used to evaluate its biodistribution. RESULTS: Several
      peptides showing a potential consensus motif were identified. The new peptide MM
      2 is stable in serum for up to 24 h. It binds to PC-3 cells, and this binding can
      be inhibited more than 70% with the unlabeled peptide. Binding to human umbilical
      vein endothelial cells (HUVECs) and PNT-2 cells is weaker, and competition (27%)
      in HUVECs is less efficient. The biodistribution showed moderate accumulation in
      tumor. CONCLUSION: Bacterial peptide display, an alternative to phage peptide
      display, can allow the identification of specific binding and stable peptides.

PMID- 15872352
TI  - Scintigraphic imaging of infectious foci with an 111In-LTB4 antagonist is based
      on in vivo labeling of granulocytes.
AB  - Radiolabeled leukotriene B4 (LTB4) antagonist DPC11870 is able to reveal
      infectious and inflammatory foci in distinct animal models. Because previous
      studies showed that accumulation of (111)In-DPC11870 in the abscess continued
      although the tracer had cleared from the circulation, we decided to investigate
      the pharmacodynamics of (111)In-DPC11870 and determine the mechanism of
      accumulation of the radiolabeled LTB4 antagonist in the abscess. METHODS: (111)In
      DPC11870 was intravenously injected in healthy New Zealand White rabbits and
      rabbits with intramuscular Escherichia coli infection. Pharmacodynamics were
      studied by serial imaging and by ex vivo counting of dissected tissues. The
      mechanism of visualization of the abscess was investigated in rabbits with
      intramuscular infection that was induced 16 h after intravenous administration of
      (111)In-DPC11870. In addition, heterologous leukocytes and bone marrow cells of a
      donor rabbit were labeled with (111)In-DPC11870 in vitro and the biodistribution
      of these in vitro radiolabeled cells was compared with that of (111)In-DPC11870
      in rabbits with an infection. RESULTS: The LTB4 antagonist (111)In-DPC11870
      revealed the intramuscular abscess in rabbits only a few hours after injection.
      Quantitative analysis of the images confirmed accumulation of (111)In-DPC11870 in
      the abscess although the compound had cleared almost completely from the
      circulation. Radioactivity concentration in the bone marrow decreased more
      rapidly in infected animals than in healthy animals. Therefore, we hypothesized
      that (111)In-DPC11870 associates with receptor-positive (bone marrow) cells and
      accumulated in the abscess because of subsequent migration from the bone marrow
      to the abscess. Accumulation of radioactivity in the abscess induced 16 h after
      (111)In-DPC11870 injection was similar to that in animals intravenously injected
      with the tracer 24 h after induction of the abscess (0.37 +/- 0.16 percentage
      injected dose [%ID]/g). Moreover, differences in radioactivity concentration in
      the bone marrow of healthy and infected animals (0.67 +/- 0.29 %ID/g and 0.15 +/-
      0.03 %ID/g at 24 h, respectively, after injection) supported our hypothesis.
      Additional studies with peripheral blood leukocytes and bone marrow cells that
      were labeled ex vivo with (111)In-DPC11870 showed the ability of these cells to
      migrate to the abscess (0.40 %ID/g and 0.52 %ID/g for (111)In-DPC11870 bone
      marrow cells and (111)In-DPC11870 peripheral blood leukocytes, respectively, 24 h
      after injection). CONCLUSION: The (111)In-labeled LTB4 antagonist DPC11870
      accumulates in infectious and inflammatory foci because of binding to LTB4
      receptors expressed on activated hematopoietic cells that subsequently migrate to
      the site of infection, which leads to visualization of the infectious lesions.

PMID- 15872353
TI  - Enhanced apoptotic reaction correlates with suppressed tumor glucose utilization
      after cytotoxic chemotherapy: use of 99mTc-Annexin V, 18F-FDG, and histologic
      evaluation.
AB  - Cancer chemotherapy enhances the apoptosis, whereas apoptosis is a suicidal
      mechanism requiring energy. We determined the relationship between apoptosis and
      glucose utilization during cancer chemotherapy using (99m)Tc-annexin V ((99m)Tc
      annexin A5) and (18)F-FDG and compared their uptake with histologic findings in a
      rat tumor model. METHODS: Allogenic hepatoma cells (KDH-8) were inoculated into
      the left calf muscle of male Wistar rats (WKA). Eleven days after the
      inoculation, the rats were randomly divided into 3 groups: The first group (n =
      7) received a single dose of gemcitabine (90 mg/kg, intravenously), the second
      group (n = 8) received cyclophosphamide (150 mg/kg, intraperitoneally), and the
      third group (n = 7) was untreated and served as the control group. We injected
      (99m)Tc-annexin V 48 h after the chemotherapy and then injected (18)F-FDG to all
      rats 1 h before sacrifice. Six hours after (99m)Tc-annexin V injection, the rats
      were sacrificed and the organs, including the tumor, were removed and
      radioactivity was counted. The radioactivities of (18)F and (99m)Tc in the organs
      were determined using normalization by tissue weight. Histologic evaluation by
      the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick
      end labeling (TUNEL) method and the immunostaining of glucose transporter-1 (GLUT
      1) were also performed to obtain the indices of apoptosis and glucose
      utilization, respectively. The rate of positively stained cells was calculated
      and analyzed statistically. RESULTS: After chemotherapy using gemcitabine and
      cyclophosphamide, the (99m)Tc-annexin V uptake (percentage injected dose per gram
      x kg [(%ID/g) x kg]; mean +/- SD) in tumor increased significantly (0.062 +/-
      0.012 (%ID/g) x kg in the gemcitabine-treated group and 0.050 +/- 0.012 (%ID/g) x
      kg in the cyclophosphamide group vs. 0.031 +/- 0.005 (%ID/g) x kg in the control
      group; P < 0.01). In contrast, the (18)F-FDG in tumor decreased significantly
      (0.483 +/- 0.118 (%ID/g) x kg in the gemcitabine group and 0.583 +/- 0.142
      (%ID/g) x kg in the cyclophosphamide group) compared with that in the control
      group (0.743 +/- 0.084 (%ID/g) x kg; P < 0.01). In addition, (18)F-FDG uptake in
      tumor negatively correlated with (99m)Tc-annexin V uptake (r = -0.75; P < 0.01).
      In the gemcitabine and cyclophosphamide groups, the rate of TUNEL positively
      stained cells was significantly higher than that in the control group (10.2% +/-
      1.7% and 8.0% +/- 1.5% vs. 5.2% +/- 1.5%; P < 0.01), whereas the GLUT-1
      expression level showed no definite changes in histologic analyses. CONCLUSION:
      These data indicate that an enhanced apoptotic reaction correlated with
      suppressed tumor glucose utilization after cytotoxic chemotherapy as determined
      using radiotracers and histologic evaluation. The increase in (99m)Tc-annexin V
      and the decrease in (18)F-FDG in tumor can be useful markers for predicting
      therapeutic outcomes and for prognosis at the early stage of chemotherapy.

PMID- 15872354
TI  - 5-[123I/125I]iodo-2'-deoxyuridine in metastatic lung cancer: radiopharmaceutical
      formulation affects targeting.
AB  - This study assesses targeting of lung metastases in mice with the radioiodinated
      thymidine analog 5-[(123)I/(125)I]iodo-2'-deoxyuridine ((123)I-IUdR/(125)I-IUdR),
      formulated with varying amounts of tributyltin precursor and injected
      intravenously. METHODS: Six- to 8-wk-old C57BL/6 mice were injected intravenously
      with B16F10 melanoma cells. Two weeks later, when lung tumors were established,
      the animals were injected intravenously with (125)I-IUdR synthesized using 1, 35,
      100, 150, 200, or 250 microg 5-tributylstannyl-2'-deoxyuridine (SnUdR) in the
      presence of an oxidant. Nontumor-bearing mice were also injected with these
      formulations and served as control animals. Twenty-four hours later, the animals
      were killed, and the radioactivity associated with the lungs and other tissues
      was measured in a gamma-counter. The percentage injected dose per gram tissue
      (%ID/g) and tumor-to-nontumor ratios (T/NT ratios) were calculated. Phosphor
      imaging was done on lungs from tumor-bearing and nontumor-bearing mice injected
      with (125)I-IUdR formulated with each tin precursor concentration. Scintigraphy
      was also performed 3 and 24 h after intravenous injection of (123)I-IUdR.
      RESULTS: The %ID/g (125)I-IUdR was higher in lungs of tumor-bearing animals than
      in lungs of control animals. Although the increase in SnUdR present led to a
      small but statistically significant decrease in the radioactive content of normal
      lungs, a 3-fold increase was observed in the lungs of tumor-bearing animals with
      radiopharmaceutical formulated with 100 microg SnUdR (5 microg per mouse). This
      enhancement in radioactive uptake by the lungs led to approximately 14-fold
      increases in T/NT ratios. Phosphor imaging ((125)I-IUdR) of lungs as well as
      scintigraphy ((123)I-IUdR) of whole animals substantiated these findings.
      CONCLUSION: The formulation for the synthesis of radio-IUdR that leads to the
      highest %ID/g in tumor and the best T/NT ratio has been identified. Further
      studies are required to determine the factors responsible for specific
      enhancement in IUdR tumor uptake.

PMID- 15872355
TI  - Structural requirements for in vivo detection of cell death with 99mTc-annexin V.
AB  - (99m)Tc-Annexin V is used to image cell death in vivo via high-affinity binding
      to exposed phosphatidylserine. We investigated how changes in membrane-binding
      affinity, molecular charge, and method of labeling affected its biodistribution
      in normal mice and its uptake in apoptotic tissues. METHODS: An endogenous Tc
      chelation site (Ala-Gly-Gly-Cys-Gly-His) was added to the N-terminus of annexin V
      to create annexin V-128. The membrane-binding affinity of annexin V-128 was then
      progressively reduced by 1-4 mutations in calcium-binding sites. In addition,
      mutations were made in other residues that altered molecular charge without
      altering membrane-binding affinity. All mutant proteins were labeled with (99m)Tc
      at the same N-terminal endogenous chelation site. Wild-type annexin V was also
      labeled with (99m)Tc after derivatization with hydrazinonicotinamide (HYNIC).
      Radiolabeled proteins were tested for biodistribution in normal mice and in mice
      treated to induce apoptosis of the liver. RESULTS: Comparison of (99m)Tc-annexin
      V-128 with (99m)Tc-HYNIC-annexin V showed that the protein labeled at the
      endogenous chelation site had the same or higher uptake in apoptotic tissues,
      while showing 88% lower renal uptake at 60 min after injection. The blood
      clearance of annexin V was unaffected by changes in either the membrane-binding
      affinity or the molecular charge. Kidney uptake was unaffected by changes in
      binding affinity. In marked contrast, uptake in normal liver and spleen decreased
      markedly as affinity decreased. The same pattern was observed in animals treated
      with cycloheximide to induce apoptosis. Control experiments with charge mutants
      showed that the effects seen with the affinity mutants were not due to the
      concomitant change in molecular charge that occurs in these mutants. CONCLUSION:
      (a) All four domains of annexin V are required for optimal uptake in apoptotic
      tissues; molecules with only 1 or 2 active domains are unlikely to be suitable
      for imaging of cell death in vivo. (b) Uptake in normal liver and spleen is
      specific (dependent on phosphatidylserine-binding affinity), whereas renal uptake
      is nonspecific. (c) (99m)Tc-Annexin V-128 detects cell death as well as (99m)Tc
      HYNIC-annexin V, while showing 88% less renal retention of radioactivity due to
      much more rapid urinary excretion of radioactivity.

PMID- 15872357
TI  - Species differences of bombesin analog interactions with GRP-R define the choice
      of animal models in the development of GRP-R-targeting drugs.
AB  - The biologic profiles of [(99m)Tc]Demobesin 1 ([(99m)Tc-N(4)(0-1),bzlg(0),d
      Phe(6),Leu-NHEt(13),des-Met(14)]BB(6-14)) and [(111)In]Z-070 were compared using
      various gastrin-releasing peptide receptor GRP-R)-expressing tissues of human and
      animal origin. METHODS: The binding affinities of Demobesin 1, Z-070, and its
      metallated analogs were determined by receptor autoradiography on human cancer
      biopsy and mouse pancreas samples and by binding assays in rat AR4-2J and human
      PC-3 cell membranes. Biodistribution of [(99m)Tc]Demobesin 1 and [(111)In]Z-070
      was compared in nude mice bearing AR4-2J and PC-3 xenografts. RESULTS: Demobesin
      1, Z-070, and metallated Z-070 showed high affinity for the rat GRP-R in AR4-2J
      cell membranes (50% inhibitory concentration values = 0.17-0.45 nmol/L). In human
      PC-3 cell membranes, Demobesin 1 showed 11- to 15-fold higher affinity than the Z
      070 peptides. These data were corroborated by results from human cancers and
      mouse pancreas. In AR4-2J and PC-3 tumor-bearing mice, [(99m)Tc]Demobesin 1 and
      [(111)In]Z-070 displayed similar uptake in the rat tumor. However, in the human
      PC-3 xenografts, [(99m)Tc]Demobesin 1 showed a 2- to 3-fold higher uptake than
      [(111)In]Z-070. CONCLUSION: Considerable differences between rat or mouse and
      human GRP-R-expressing tissues were found for the in vitro and in vivo
      characteristics of 2 radiolabeled bombesin analogs. This finding may have a
      significant impact in the selection of experimental tools in the development of
      bombesin analogs for GRP-R-targeting applications in humans.

PMID- 15872356
TI  - In vivo detection of stem cells grafted in infarcted rat myocardium.
AB  - The evaluation of stem cell-mediated cardiomyoplasty by noninvasive in vivo
      imaging is critical for its clinical application. We hypothesized that dual
      tracer small-animal SPECT would allow simultaneous imaging of (99m)Tc-sestamibi
      to assess myocardial perfusion and of (111)In-labeled stem cells to delineate
      stem cell engraftment. METHODS: Three to 4 million rat embryonic cardiomyoblasts
      (H9c2 cells) were labeled with 11.1-14.8 MBq (0.3-0.4 mCi) of (111)In
      oxyquinoline and then injected into the border zones of infarcted myocardium of
      rats. (111)In images were acquired with a SPECT scanner 2, 24, 48, 72, and 96 h
      after the stem cells were injected into the infarcted myocardium. To visualize
      the perfusion deficit in the infarcted myocardium, we injected 74 MBq (2 mCi) of
      (99m)Tc-sestamibi (Cardiolite) intravenously 48 h after grafting. Dual-isotope
      pinhole SPECT was used to image (99m)Tc-sestamibi uptake simultaneously with
      (111)In to delineate retention of (111)In-labeled stem cells. The presence of
      labeled stem cells was confirmed by autoradiography and histology. RESULTS: SPECT
      of (99m)Tc-sestamibi was used to delineate perfusion deficits and infarcted
      myocardium. Bull's-eye plots indicated that the (111)In signal from the labeled
      stem cells overlapped the perfusion deficits identified from the (99m)Tc
      sestamibi images. The (111)In signal associated with the radiolabeled stem cells
      could be detected with SPECT of the heart for 96 h after engraftment. CONCLUSION:
      This study demonstrated the feasibility of using dual-isotope pinhole SPECT for
      high-resolution detection of perfusion deficits with (99m)Tc-sestamibi and with
      (111)In-labeled stem cells grafted into the region of the infarct.

PMID- 15872358
TI  - Effects of Pax8 and TTF-1 thyroid transcription factor gene transfer in hepatoma
      cells: imaging of functional protein-protein interaction and iodide uptake.
AB  - The thyroid transcription factors TTF-1 and Pax8 cooperate in the transcriptional
      activation of thyroid-specific genes such as thyroglobulin (Tg), thyroperoxidase
      (TPO), and sodium/iodide symporter (NIS). METHODS: Dog TTF-1 (dTTF-1) and the
      human Pax8 (hPax8) gene were transfected in Morris hepatoma (MH3924A) cells to
      investigate (a) the possible visualization of functional protein-protein
      interaction and (b) the induction of thyroid-specific gene expression. In MH3924A
      cell lines expressing dTTF-1, hPax8, or both, the activation of human Tg (hTg),
      human TPO (hTPO), or rat NIS (rNIS) promoter/enhancer was measured using firefly
      luciferase reporter constructs. Furthermore, the possible induction of thyroid
      specific genes was investigated in iodide uptake and reverse transcription
      polymerase chain reaction (RT-PCR) experiments. RESULTS: Low transcriptional
      activation of these constructs was observed in cells expressing either hPax8 or
      dTTF-1 alone. In contrast, the hTg and hTPO and, to a lesser extent, the rNIS
      regulatory region were significantly activated in cell lines expressing both
      transcription factors. Imaging the transcriptional activation of the thyroid
      specific regulatory regions by Pax8 and TTF-1 was possible in nude mice implanted
      with MHhPax8dTTF-1 cells using a cooled charge-coupled device camera. Na(125)I
      uptake experiments and RT-PCR showed no effect of hPax8 and dTTF-1 on endogenous
      thyroid-specific gene expression in genetically modified cells. CONCLUSION: The
      activation of thyroid-specific promoter/enhancer elements in Morris hepatoma
      cells depends on the functional interaction of hPax8 and dTTF-1. The cooperation
      of these 2 transcription factors can be visualized in vitro as well as in vivo.
      With regard to a possible application for radioiodine therapy, further
      modifications are required.

PMID- 15872359
TI  - Accurate dosimetry in 131I radionuclide therapy using patient-specific, 3
      dimensional methods for SPECT reconstruction and absorbed dose calculation.
AB  - (131)I radionuclide therapy studies have not shown a strong relationship between
      tumor absorbed dose and response, possibly due to inaccuracies in activity
      quantification and dose estimation. The goal of this work was to establish the
      accuracy of (131)I activity quantification and absorbed dose estimation when
      patient-specific, 3-dimensional (3D) methods are used for SPECT reconstruction
      and for absorbed dose calculation. METHODS: Clinically realistic voxel-phantom
      simulations were used in the evaluation of activity quantification and dosimetry.
      SPECT reconstruction was performed using an ordered-subsets expectation
      maximization (OSEM) algorithm with compensation for scatter, attenuation, and 3D
      detector response. Based on the SPECT image and a patient-specific density map
      derived from CT, 3D dosimetry was performed using a newly implemented Monte Carlo
      code. Dosimetry was evaluated by comparing mean absorbed dose estimates
      calculated directly from the defined phantom activity map with those calculated
      from the SPECT image of the phantom. Finally, the 3D methods were applied to a
      radioimmunotherapy patient, and the mean tumor absorbed dose from the new
      calculation was compared with that from conventional dosimetry obtained from
      conjugate-view imaging. RESULTS: Overall, the accuracy of the SPECT-based
      absorbed dose estimates in the phantom was >12% for targets down to 16 mL and up
      to 35% for the smallest 7-mL tumor. To improve accuracy in the smallest tumor,
      more OSEM iterations may be needed. The relative SD from multiple realizations
      was <3% for all targets except for the smallest tumor. For the patient, the mean
      tumor absorbed dose estimate from the new Monte Carlo calculation was 7% higher
      than that from conventional dosimetry. CONCLUSION: For target sizes down to 16
      mL, highly accurate and precise dosimetry can be obtained with 3D methods for
      SPECT reconstruction and absorbed dose estimation. In the future, these methods
      can be applied to patients to potentially establish correlations between tumor
      regression and the absorbed dose statistics from 3D dosimetry.

PMID- 15872361
TI  - Correction methods for random coincidences in fully 3D whole-body PET: impact on
      data and image quality.
AB  - With the advantages of the increased sensitivity of fully 3-dimensional (3D) PET
      for whole-body imaging come the challenges of more complicated quantitative
      corrections and, in particular, an increase in the number of random coincidences.
      The most common method of correcting for random coincidences is the real-time
      subtraction of a delayed coincidence channel, which does not add bias but
      increases noise. An alternative approach is the postacquisition subtraction of a
      low-noise random coincidence estimate, which can be obtained either from a
      smoothed delayed coincidence sinogram or from a calibration scan or directly
      estimated. Each method makes different trade-offs between noise amplification,
      bias, and data-processing requirements. These trade-offs are dependent on
      activity injected, the local imaging environment (e.g., near the bladder), and
      the reconstruction algorithm. METHODS: Using fully 3D whole-body simulations and
      phantom studies, we investigate how the gains in noise equivalent count (NEC)
      rates from using a noiseless random coincidence estimation method are translated
      to improvements in image signal-to-noise ratio (SNR). The image SNR, however,
      depends on the image reconstruction method and the local imaging environment.
      RESULTS: We show that for fully 3D whole-body imaging using a particular set of
      scanners and clinical protocols, a low-noise estimate of random coincidences
      improves sinogram and image SNRs by approximately 15% compared with online
      subtraction of delayed coincidences. CONCLUSION: A 15% improvement in image SNR
      arises from a 32% increase in the NEC rate. Thus, scan duration can be reduced by
      25% while still maintaining a constant total acquired NEC.

PMID- 15872360
TI  - Prediction of myelotoxicity based on bone marrow radiation-absorbed dose:
      radioimmunotherapy studies using 90Y- and 177Lu-labeled J591 antibodies specific
      for prostate-specific membrane antigen.
AB  - In radioimmunotherapy, myelotoxicity due to bone marrow radiation-absorbed dose
      is the predominant factor and frequently is the dose-limiting factor that
      determines the maximum tolerated dose (MTD). With (90)Y- and (131)I-labeled
      monoclonal antibodies, it has been reported that myelotoxicity cannot be
      predicted on the basis of the amount of radioactive dose administered or the bone
      marrow radiation-absorbed dose (BMrad), estimated using blood radioactivity
      concentration. As part of a phase I dose-escalation study in patients with
      prostate cancer with (90)Y-DOTA-J591 (DOTA = 1,4,7,10-tetraazacyclododecane
      N,N',N'',N'''-tetraacetic acid) ((90)Y-J591) and (177)Lu-DOTA-J591 ((177)Lu
      J591), we evaluated the potential value of several factors in predicting
      myelotoxicity. METHODS: Seven groups of patients (n = 28) received 370-2,775
      MBq/m(2) (10-75 mCi/m(2)) of (177)Lu-J591 and 5 groups of patients (n = 27)
      received 185-740 MBq (5-20 mCi/m(2)) of (90)Y-J591. Pharmacokinetics and imaging
      studies were performed for 1-2 wk after (177)Lu treatment, whereas patients
      receiving (90)Y had these studies performed with (111)In-DOTA-J591 ((111)In-J591)
      as a surrogate. The BMrad was estimated based on blood radioactivity
      concentration. Myelotoxicity consisting of thrombocytopenia or neutropenia was
      graded 1-4 based on criteria of the National Cancer Institute. RESULTS: Blood
      pharmacokinetics are similar for both tracers. The radiation dose (mGy/MBq) to
      the bone marrow was 3 times higher with (90)Y (0.91 +/- 0.43) compared with that
      with (177)Lu (0.32 +/- 0.10). The MTD was 647.5 MBq/m(2) with (90)Y-J591 and
      2,590 MBq/m(2) with (177)Lu-J591. The percentage of patients with myelotoxicity
      (grade 3-4) increased with increasing doses of (90)Y (r = 0.91) or (177)Lu (r =
      0.92). There was a better correlation between the radioactive dose administered
      and the BMrad with (177)Lu (r = 0.91) compared with that with (90)Y (r = 0.75).
      In addition, with (177)Lu, the fractional decrease in platelets (FDP) correlates
      well with both the radioactive dose administered (r = 0.88) and the BMrad (r =
      0.86). In contrast, with (90)Y, there was poor correlation between the FDP and
      the radioactive dose administered (r = 0.20) or the BMrad (r = 0.26). Similar
      results were also observed with white blood cell toxicity. CONCLUSION: In
      patients with prostate cancer, myelotoxicity after treatment with (177)Lu-J591
      can be predicted on the basis of the amount of radioactive dose administered or
      the BMrad. The lack of correlation between myelotoxicity and (90)Y-J591 BMrad may
      be due to several factors. (90)Y-J591 may be less stable in vivo and, as a
      result, higher amounts of free (90)Y may be localized in the bone. In addition,
      the cross-fire effect of high-energy beta(-)-particles within the bone and the
      marrow may deliver radiation dose nonuniformly within the marrow.

PMID- 15872362
TI  - Correction of photon attenuation and collimator response for a body-contouring
      SPECT/CT imaging system.
AB  - (111)In-Capromab pendetide imaging is indicated for postprostatectomy patients at
      risk for residual or recurrent disease. However, this study is complicated by
      relatively long times for tumor uptake and background washout that require
      imaging to be performed several days after radiopharmaceutical administration. In
      addition, (111)In-capromab pendetide demonstrates uptake in normal structures
      that produce images that are interpreted best using correlation with anatomic
      imaging. Finally, the visual quality of radionuclide imaging can be improved with
      corrections for photon attenuation and for the geometric response of the
      radionuclide collimator. Therefore, we have evaluated the advantages of using a
      commercially available dual-modality SPECT/CT system. In this article, we
      evaluate a novel iterative reconstruction algorithm using the SPECT/CT data
      obtained from phantoms and (111)In-capromab pendetide patient studies. METHODS:
      Phantom data acquired with the dual-head SPECT camera were reconstructed using
      both filtered backprojection (FBP) and an iterative maximum-likelihood
      expectation maximization (MLEM) algorithm incorporating corrections for (a)
      attenuation coefficient at the effective energy of the radionuclide (either
      (99m)Tc or (111)In) and (b) collimator response based on experimentally measured
      depth-dependent spatial resolution of the camera. The collimator response model
      used the coregistered CT image to estimate the source-target distances produced
      by the patient-contouring logic of the SPECT camera. Spatial resolution was
      measured using SPECT images of 2 line sources and uniformity from a uniform
      cylindric tank. Clinical (111)In-capromab pendetide SPECT/CT data were acquired
      according to the radiopharmaceutical manufacturer's protocol. Region-of-interest
      (ROI) analysis of a transverse slice at the level of the sacral base produced
      mean, median, maximum, and minimum counts per pixel for bone marrow and
      surrounding soft-tissue ROIs. Ratios of the mean capromab pendetide uptake within
      marrow to uptake within soft tissue were compared for images reconstructed with
      FBP versus that obtained from the MLEM method with photon attenuation and
      collimator response corrections. RESULTS: The source-target distances
      reconstructed from the patient-specific CT image agreed well with the
      corresponding values recorded manually from the camera display unit. This
      information was incorporated into the iterative reconstruction algorithms and
      improved the quality of SPECT images from phantoms and patients versus SPECT
      images reconstructed without the depth-dependent collimator response model.
      Qualitatively, SPECT images reconstructed with corrections for photon attenuation
      and collimator response showed less background activity and improved target
      contrast compared with those images reconstructed with FBP. The target-to
      background ratio (marrow uptake-to-soft-tissue uptake) was significantly better
      using MLEM reconstruction than with FBP when mean uptake values were measured.
      CONCLUSION: A priori anatomic data can be used to enhance the quality of the
      SPECT image when reconstructed using iterative techniques (e.g., MLEM) that use
      the CT data to produce a patient-specific attenuation map and a collimator
      response model based on the body contour produced during the SPECT acquisition.

PMID- 15872363
TI  - A new strategy to screen molecular imaging probe uptake in cell culture without
      radiolabeling using matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry.
AB  - Numerous new molecular targets for diseases are rapidly being identified and
      validated in the postgenomic era, urging scientists to explore novel techniques
      for accelerating molecular probe development. In this study, matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was
      investigated as a potential tool for high-throughput screening and
      characterization of molecular imaging probes. Specifically, MALDI-TOF-MS was used
      to screen a small library of phosphonium cations for their ability to accumulate
      in cells. METHODS: C6 cells incubated with phosphonium cations at room
      temperature were collected and lysed for experiments. Calibration curves for the
      internal standard, methyltriphenyl phosphonium, and for tetraphenylphosphonium
      bromide (TPP) and other phosphonium cations were first established. The time
      course of TPP uptake by C6 cells was then quantified using both MALDI-TOF-MS and
      liquid scintillation counting with (3)H-TPP. In addition, MALDI-TOF-MS was used
      to screen a library of 8 phosphonium cations and subsequently rank their ability
      to penetrate membranes and accumulate in cells. Finally, the accumulation of 4
      fluorophenyltriphenyl phosphonium (FTPP) in the membrane potential-modulated
      cells was also measured by MALDI-TOF-MS. RESULTS: MALDI-TOF-MS spectra clearly
      revealed that TPP was easily identified from cell lysates even as early as 10 min
      after incubation and that levels as low as 0.11 fmol of TPP per cell could be
      detected, suggesting the high sensitivity of this technique. The time course of
      TPP influx determined by both MALDI-TOF-MS and radioactivity counting showed no
      statistically significant difference (P > 0.05 for all time points). These data
      validated MALDI-TOF-MS as an alternative approach for accurately measuring uptake
      of phosphonium cations by cells. TPP and FTPP demonstrated greater accumulation
      in cells than did the other cations evaluated in this study. Furthermore, uptake
      profiles suggested that FTPP preserves the membrane potential-dependent uptake
      property of TPP in cell cultures. Taken together, these data justify further
      synthesis and evaluation of (18)F-FTPP as a molecular probe for imaging
      mitochondrial dysfunction. CONCLUSION: These results demonstrate that MALDI-TOF
      MS is a powerful analytic tool for rapid screening and characterization of
      phosphonium cations as molecular probes. This technique can potentially be
      applied to the evaluation of other imaging probes or drugs and thus may
      facilitate their rational design and development.

PMID- 15872364
TI  - Melanoma targeting with DOTA-alpha-melanocyte-stimulating hormone analogs:
      structural parameters affecting tumor uptake and kidney uptake.
AB  - Radiolabeled analogs of alpha-melanocyte-stimulating hormone (alpha-MSH) are
      potential candidates for the diagnosis and therapy of melanoma metastases. After
      our recent observation that a linear octapeptide alpha-MSH analog incorporating
      the metal chelator 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid
      (DOTA) at the C-terminal lysine, [Nle(4),Asp(5),d-Phe(7),Lys(11)(DOTA)]-alpha
      MSH(4-11) (DOTA-NAPamide), showed high accumulation in melanomas in a mouse
      model, low uptake in normal tissues, and moderate uptake in the kidneys, we
      attempted to identify the structural parameters influencing tumor uptake versus
      kidney uptake. METHODS: We designed a series of novel DOTA-alpha-MSH analogs
      differing from DOTA-NAPamide by small alterations, such as the position of DOTA
      in the peptide, hydrophobicity, and charge, by modifying the C-terminal Lys(11)
      residue. They were evaluated both for their melanocortin type 1 receptor (MC1R)
      binding potency and for their biodistribution by use of the B16F1 melanoma mouse
      model. RESULTS: When DOTA was shifted to the N terminus of the peptide, a 3-fold
      increase in kidney retention was obtained. However, when the epsilon-amino group
      of the Lys(11) residue was acetylated in addition to the DOTA relocation, kidney
      uptake returned to the low values obtained with DOTA-NAPamide; this result
      indicated that neutralization of the epsilon-amino group positive charge of the
      Lys(11) residue rather than the position of DOTA accounted for the low kidney
      retention. Unexpectedly, no further reduction in kidney uptake was obtained by
      the introduction of 1 or 2 negative charges on Lys(11). Melanoma uptake was in
      accordance with MC1R affinity; the highest values were obtained for peptides
      bearing carboxy-terminal amidation and positioning of DOTA. CONCLUSION: The
      kidney uptake of DOTA-alpha-MSH analogs could be considerably reduced, without
      affecting MC1R affinity, by altering (neutralizing) the charge of the Lys(11)
      residue. Accordingly, the resulting peptides exhibited a high ratio of tumor
      uptake to kidney uptake that is favorable for diagnostic and therapeutic
      applications. These structure-activity data may help to improve the performance
      of DOTA-alpha-MSH analogs and other radiopeptides.

PMID- 15872365
TI  - DNA uptake of 131I-iododeoxyuridine.

PMID- 15872366
TI  - Why is the resolution of the Discovery PET/CT camera so poor?

PMID- 15872367
TI  - Blood and bone marrow dosimetry in radioiodine therapy of thyroid cancer.

PMID- 15872368
TI  - Blood dosimetry and dose-rate effects after radioiodine therapy of differentiated
      thyroid cancer.

PMID- 15872369
TI  - Blood and bone marrow dosimetry in radioiodine therapy of differentiated thyroid
      cancer after stimulation with rhTSH.

PMID- 15872370
TI  - Inducible nitric oxide synthase immunoreactivity in the granulomatous intestinal
      lesions of naturally occurring bovine Johne's disease.
AB  - Inducible nitric oxide synthase (iNOS) is important in the control of a number of
      intracellular pathogens, including mycobacteria, and is a marker of classic
      macrophage activation. In human granulomatous diseases such as leprosy, a
      spectrum of granulomatous lesions is described, ranging from the tuberculoid to
      lepromatous types. Tuberculoid granulomas are associated with enhanced iNOS
      production and improved clinical outcomes over the lepromatous types. The aim of
      this study is to determine whether an association exists between morphology of
      bovine Johne's disease granulomas and lesion macrophage effector functions. To
      accomplish this, we retrospectively evaluated 24 cases of bovine Johne's disease.
      In each case, we recorded the predominant granuloma morphology and evaluated iNOS
      immunoreactivity and bacterial burden by acid-fast stains and mycobacterial
      immunolabeling. The results of this study demonstrate that all cases had
      granulomas with features most similar to the lepromatous type. This morphology
      correlated with heavy bacterial burdens demonstrated by acid-fast staining and
      mycobacterial immunoreactivity. None of the cases had high expression of iNOS in
      mycobacterial-positive granulomas. When iNOS immunoreactivity was identified, it
      was usually located near the crypts and was distinct from the granulomatous foci.

PMID- 15872371
TI  - Expression of maspin in mammary gland tumors of the dog.
AB  - Maspin is a serine protease inhibitor that inhibits tumor invasion and metastasis
      in human breast cancer and is consistently expressed by mammary myoepithelial
      cells (MECs). To analyze the value of maspin as a marker of the MEC layer of the
      normal and tumoral canine mammary gland, the immunohistochemical expression of
      maspin was studied in formalin-fixed tissues from 55 benign and malignant tumors
      (40 tumors also contained the surrounding normal mammary gland) using a
      commercially available monoclonal antibody. Periacinar and periductal MECs of all
      40 normal mammary glands were stained by the anti-human maspin monoclonal
      antibody, and immunoreactivity was observed in the nucleus and cytoplasm of these
      cells. In addition, maspin was found in 53 (98%) of the tumors studied, reacting
      with the MECs in 100% of benign tumors and 93% of malignant tumors and to the
      epithelial cells of 16% of benign and 73% of malignant tumors. In the MEC
      compartment, immunoreactivity was observed in the cytoplasm of hypertrophic MECs,
      fusiform MECs, stellate MECs, rounded (myoepithelial) cells, and chondroblasts.
      In the epithelial cell compartment, immunoreactivity was observed in the
      cytoplasm of cells with and without squamous differentiation. Stromal
      myofibroblasts were unreactive. Maspin appears to be a very sensitive marker of
      the normal and neoplastic myoepithelium that, contrary to smooth muscle
      differentiation markers, does not stain stromal myofibroblasts. In addition, a
      subset of neoplastic epithelial cells reacted with the maspin antibody. The
      relationship between maspin expression in different cellular compartments of
      canine mammary carcinomas and the biologic aggressiveness of the disease remains
      to be elucidated.

PMID- 15872372
TI  - Mapping PrPSc propagation in experimental and natural scrapie in sheep with
      different PrP genotypes.
AB  - Twenty-one orally inoculated and seven naturally infected sheep with scrapie were
      examined for PrP(Sc) in peripheral tissues and in the central nervous system
      (CNS), using immunohistochemistry. In the inoculated group, VRQ (valine at codon
      136, arginine at codon 154 and glutamine at codon 171)/VRQ sheep generally had a
      greater accumulation of the pathologic form of prion protein (PrP(Sc)) in
      peripheral tissues, as compared with VRQ/ARQ (alanine at codon 136, arginine at
      codon 154, and glutamine at codon 171) animals at corresponding time points after
      inoculation. PrP(Sc) was not detected in the ileal Peyer's patch, the spleen, the
      superficial cervical lymph node, and peripheral nervous tissues of several
      inoculated VRQ/ARQ animals. All inoculated VRQ/VRQ sheep, but only one of eight
      inoculated VRQ/ARQ animals, were PrP(Sc)-positive in the CNS. Thus, the
      propagation of PrP(Sc) seemed slower and more limited in VRQ/ARQ animals. Tissue
      and cellular localization of PrP(Sc) suggested that PrP(Sc) was disseminated
      through three different routes. PrP(Sc)-positive cells in lymph node sinuses and
      in lymphatics indicated spreading by lymph. The sequential appearance of PrP(Sc)
      in the peripheral nervous system and the CNS, with satellite cells as early
      targets, suggested the periaxonal transportation of PrP(Sc) through supportive
      cells. Focal areas of vascular amyloid-like PrP(Sc) in the brain of five sheep,
      suggested the hematogenous dissemination of PrP(Sc). There was a poor correlation
      between the amount of PrP(Sc) in the CNS and clinical signs. One subclinically
      affected sheep showed widespread PrP(Sc) accumulation in the CNS, whereas three
      sheep had early clinical signs without detectable PrP(Sc) in the CNS. A VV(136)
      (homozygous for valine at codon 136) sheep inoculated with ARQ/ARR (alanine at
      codon 136, arginine at codon 154, and arginine at codon 171) tissue succumbed to
      disease, demonstrating successful heterologous transmission. Less susceptible
      sheep receiving VRQ/VRQ or ARQ/ARR material were PrP(Sc)-negative by
      immunohistochemistry, enzyme-linked immunosorbent assay, and western blot.

PMID- 15872373
TI  - The avian major histocompatibility complex influences bacterial skeletal disease
      in broiler breeder chickens.
AB  - This study evaluated bacterial skeletal disease in conjunction with the major
      histocompatibility complex (MHC) in a genetically pure line of broiler breeder
      chickens. Chickens from six broiler breeder flocks were examined for skeletal
      lesions, bacterial pathogens, and MHC genotype. During a 10-week period, eighty
      eight, 9- to 21-week-old lame chickens and 34 normal, age-matched controls were
      selected. Tenosynovitis, arthritis, and femoral or tibiotarsal (or both)
      osteomyelitis occurred in 86 of 88 (97.7%) lame chickens. Ninety-five bacterial
      isolates were obtained from 83 of 88 (94.3%) lame birds and 4 of 34 (11.8%)
      controls. Staphylococcus spp. was isolated from 72.6% of the skeletal lesions,
      predominantly Staphylococcus aureus (38.9%). MHC B complex genotypes were
      determined by hemagglutination for 88 lame birds, 34 controls, and 200 randomly
      selected birds from each of the six flocks (1,200 total). Combined chi-square
      analysis revealed that the homozygous MHC genotypes B(A4/A4) (chi(2) = 14.54, P =
      0.0063) and B(A12/A12) (chi(2) = 42.77, P = 0.0001) were overrepresented in the
      sample of symptomatic birds compared with random samples from the same flocks.
      The homozygous A4 and A12 MHC genotypes influenced flock chi-square values more
      than the corresponding heterozygotes. An MHC B complex influence on bacterial
      skeletal disease was apparent in this line of broiler breeders.

PMID- 15872374
TI  - Uterine mast cells and immunoglobulin-E antibody responses during clearance of
      Tritrichomonas foetus.
AB  - We showed earlier that Tritrichomonas foetus-specific bovine immunoglobulin
      (Ig)G1 and IgA antibodies in uterine and vaginal secretions are correlated with
      clearance of this sexually transmitted infection. Eosinophils have been noted in
      previous studies of bovine trichomoniasis but the role of mast cells and IgE
      responses have not been reported. The hypothesis that IgE and mast cell
      degranulation play a role in clearance was tested in 25 virgin heifers
      inseminated experimentally and infected intravaginally with T. foetus strain D1
      at estrus and cultured weekly. Groups were euthanatized at 3, 6, 9, or 12 weeks,
      when tissues were fixed and secretions were collected for culture and antibody
      analysis. Immunohistochemistry using a monoclonal antibody to a soluble
      lipophosphoglycan (LPG)-containing surface antigen (TF1.17) demonstrated antigen
      uptake by uterine epithelial cells. Lymphoid nodules were detected below antigen
      positive epithelium. Little IgG2 antibody was detected but IgG1, IgA, IgM, and
      IgE T. foetus-specific antibodies increased in uterine secretions at weeks 6 and
      9 after infection. This was inversely proportional to subepithelial mast cells
      numbers and most animals cleared the infection by the sampling time after the
      lowest mast cell count. Furthermore, soluble antigen was found in uterine
      epithelium above inductive sites (lymphoid nodules). Cross-linking of IgE on mast
      cells by antigen and perhaps LPG triggering appears to have resulted in
      degranulation. Released cytokines may account for production of predominantly Th2
      (IgG1 and IgE) and IgA antibody responses, which are related to clearance of the
      infection.

PMID- 15872375
TI  - Acute and chronic gas bubble lesions in cetaceans stranded in the United Kingdom.
AB  - The first evidence suggestive of in vivo gas bubble formation in cetacea,
      including eight animals stranded in the UK, has recently been reported. This
      article presents the pathologic findings from these eight UK-stranded cetaceans
      and two additional UK-stranded cetacean cases in detail. Hepatic gas-filled
      cavitary lesions (0.2-6.0 cm diameter) involving approximately 5-90% of the liver
      volume were found in four (two juvenile, two adult) Risso's dolphins (Grampus
      griseus), three (two adult, one juvenile) common dolphins (Delphinus delphis), an
      adult Blainville's beaked whale (Mesoplodon densirostris), and an adult harbour
      porpoise (Phocoena phocoena). Histopathologic examination of the seven dolphin
      cases with gross liver cavities revealed variable degrees of pericavitary
      fibrosis, microscopic, intrahepatic, spherical, nonstaining cavities (typically
      50-750 microm in diameter) consistent with gas emboli within distended portal
      vessels and sinusoids and associated with hepatic tissue compression,
      hemorrhages, fibrin/organizing thrombi, and foci of acute hepato-cellular
      necrosis. Two common dolphins also had multiple and bilateral gross renal
      cavities (2.0-9.0 mm diameter) that, microscopically, were consistent with acute
      (n = 2) and chronic (n = 1) arterial gas emboli-induced renal infarcts.
      Microscopic, bubblelike cavities were also found in mesenteric lymph node (n =
      4), adrenal (n = 2), spleen (n = 2), pulmonary associated lymph node (n = 1),
      posterior cervical lymph node (n = 1), and thyroid (n = 1). No bacterial
      organisms were isolated from five of six cavitated livers and one of one
      cavitated kidneys. The etiology and pathogenesis of these lesions are not known,
      although a decompression-related mechanism involving embolism of intestinal gas
      or de novo gas bubble (emboli) development derived from tissues supersaturated
      with nitrogen is suspected.

PMID- 15872376
TI  - Epithelial-stromal tumor of the seminal vesicles in the transgenic adenocarcinoma
      mouse prostate model.
AB  - The transgenic adenocarcinoma mouse prostate (TRAMP) model, designed for
      researching human prostatic cancer, was genetically engineered to harbor a
      transgene composed of the simian virus 40 Large-T/small-t antigen promoted by the
      rat probasin gene. In addition to prostatic neoplasms, the TRAMP mouse develops
      tumors in the seminal vesicles. This study was conducted to evaluate the
      pathology and histogenesis of TRAMP seminal vesicle neoplasms. Tissues of
      accessory sex organs harvested from 72 TRAMP mice of various ages (11-40 weeks of
      age) were fixed in neutral buffered formalin and stained with hematoxylin and
      eosin, desmin, 5-bromo-2'-deoxyuridine (BrdU, treated animals only), and SV40
      Large-T antigen (SV40-Tag). In the seminal vesicles, we found neoplastic stromal
      cells that emerged multicentrically just beneath the epithelium, densely packed
      between the epithelium and the smooth muscle layer. These stromal cells
      frequently exhibited mitotic figures and showed BrdU incorporation and SV40-Tag
      protein expression in the nuclei and immunopositivity for desmin. The
      proliferative mesenchymal cells were lined by cuboidal to columnar epithelium.
      Some of the larger papillary, polypoid lesions exhibited a phyllodes pattern
      resembling that seen in mixed epithelial-stromal tumors of the breast, prostate,
      and seminal vesicles of humans. Although the epithelium was negative for SV40-Tag
      and showed only occasional incorporation of BrdU, it clearly participated in the
      biphasic proliferation, forming papillary, cystic, and tubuloglandular
      structures. No conclusive evidence of malignancy (invasion or metastasis) was
      identified. Our recommended diagnosis of this lesion in the seminal vesicles is
      epithelial-stromal tumor.

PMID- 15872377
TI  - Usefulness of thyroid transcription factor-1 immunohistochemical staining in the
      differential diagnosis of primary pulmonary tumors of dogs.
AB  - In a previous study, we characterized the reactivity of monoclonal antibody
      (MoAb) 8G7G3/1 to thyroid transcription factor-1 (TTF-1) in canine thyroid
      tumors. In this study, we have examined the reactivity of this antibody in 120
      canine pulmonary tumors, including 78 primary epithelial tumors. Tissues had been
      fixed in formalin and routinely processed for histopathology. Nuclear staining
      for TTF-1 was detected in 64.2% of primary pulmonary epithelial tumors. The most
      common TTF-1-reactive tumor types were bronchioloalveolar carcinomas and
      bronchogenic carcinomas. Staining was diffuse, heterogeneous, or patchy.
      Nonpulmonary, metastatic epithelial tumors, except two of two thyroid carcinomas,
      did not react with antibody 8G7G3/1. Mesotheliomas and other mesenchymal tumors
      were also negative for this marker. A reduction or loss of reactivity was
      apparent in pulmonary epithelial tumors archived in paraffin blocks for 7-8
      years. There was slight reduction in the number of positive cells or the
      intensity of the reaction in control tissues fixed longer than 1 week. On the
      basis of our limited studies and the human literature, it appears that MoAb
      8G7G3/1 to TTF-1 is a highly specific (with the exception of thyroid tumors) and
      moderately sensitive marker for canine pulmonary epithelial tumors.

PMID- 15872378
TI  - Morphologic features and development of granulomatous vasculitis in feline
      infectious peritonitis.
AB  - Feline infectious peritonitis (FIP) is a fatal, coronavirus (CoV)-induced
      systemic disease in cats, characterized by granulomas in organs and granulomatous
      vasculitis. This study describes the morphologic features of granulomatous
      vasculitis in FIP as well as its development in the course of monocyte-associated
      feline CoV (FCoV) viremia in five naturally infected Domestic Shorthair cats with
      FIP. Monocyte-associated FCoV viremia was demonstrated by immunohistology, RNA in
      situ hybridization, and electron micropscopy. Granulomatous phlebitis at
      different stages of development was observed. Vasculitic processes ranged from
      attachment and emigration of FCoV-infected monocytes to vascular/perivascular
      granulomatous infiltrates with destruction of the vascular basal lamina.
      Monocytes as well as perivascular macrophages were activated because they were
      strongly positive for CD18 and expressed cytokines (tumor necrosis factor-alpha
      and interleukin-1beta) and matrix metalloproteinase-9. In addition, general
      activation of endothelial cells, represented by major histocompatibility complex
      II upregulation, was observed in all cases. These results confirm FIP as a
      monocyte-triggered systemic disease and demonstrate the central role of activated
      monocytes in FIP vasculitis.

PMID- 15872379
TI  - Hepatobiliary neuroendocrine carcinoma in cats: a clinicopathologic,
      immunohistochemical, and ultrastructural study of 17 cases.
AB  - Hepatobiliary neuroendocrine carcinoma was diagnosed in 17 cats in a period of 10
      years. Seven tumors were of intrahepatic origin, one of which was a composite
      containing components of epithelial and neuroendocrine carcinoma. Nine tumors
      were of extrahepatic origin, and one tumor was located in the gall-bladder. The
      cats were adult and geriatric, and the male : female ratio varied according to
      tumor group. Hepatomegaly, anorexia, weight loss, and vomiting were the most
      common clinical signs observed in the cats with hepatic neuroendocrine carcinoma.
      The cats with extrahepatic neuroendocrine carcinoma showed these signs plus
      icterus (5/9) and high concentrations of hepatic enzymes. Histologically, the
      hepatic neuroendocrine carcinomas had two patterns, one with acinar structures
      separated by vascular stroma lined by cuboidal or columnar cells and the other
      solid with groups of anaplastic cells separated by vascular stroma. The composite
      tumor consisted of both bile duct carcinoma and neuroendocrine carcinoma. The
      extrahepatic neuroendocrine carcinomas and the gallbladder neuroendocrine
      carcinoma were characterized by solid sheets or groups of round to oval cells
      with vascular or fibrovascular stroma. Immunohistochemical examination of 10 of
      the neuroendocrine carcinomas revealed that all 10 stained with neuron-specific
      enolase; one bile duct carcinoma and the gallbladder carcinoma stained with
      chromogranin; four of five bile duct carcinomas and the gall bladder carcinoma
      stained with synaptophysin; and one bile duct carcinoma stained with gastrin. One
      cat with hepatic carcinoma had duodenal ulcer; in this cat, ultrastructural
      studies showed neurosecretory granules leading to the diagnosis of Zollinger
      Ellison syndrome. In four cats in which necropsy was permitted, carcinomatosis
      (4/4), lymph nodes (4/4), lungs (2/4), and intestines (1/4) were the metastatic
      sites. Fourteen of the 17 cats were euthanatized during or immediately after
      surgery.

PMID- 15872380
TI  - Correlation of virus replication in tissues with histologic lesions in Atlantic
      salmon experimentally infected with infectious salmon anemia virus.
AB  - We have studied the replication of virus in tissues and development of lesions
      associated with infectious salmon anemia virus (ISAV) infection in Atlantic
      salmon using in situ hybridization (ISH) with a riboprobe targeting ISAV RNA
      segment 7 messenger RNA. Fish were infected with three ISAV isolates (U5575-1,
      RPC-01-0593-1, Norway 810/9/99) and then euthanatized sequentially at 3, 6, 10,
      and 13 days postinoculation (dpi) and thereafter once a week for 8 weeks. Severe
      histopathologic lesions were observed in tissues from all groups beginning at the
      onset of mortality. The severe histopathologic lesions correlated with maximum
      intensity and frequency of ISH signals (P < 0.001). There was a strong
      association between the hybridization signals and severity of lesions in the
      liver, kidney, and heart (R = 0.81, 0.70, and 0.78, respectively; P < 0.001). The
      distribution of ISH signals indicated the presence of a viremia because signals
      were observed predominantly in individual blood cells and endothelial cells, and
      possibly hematopoietic cells of head kidney, but not in the necrotic hepatocytes
      and renal epithelium. Of the organs sampled, the heart was the first and last to
      show ISH signals, possibly because of increased activity of the endocardial
      endothelial cells and the underlining macrophages, which continuously trap and
      remove circulating virus, and therefore represents the best tissue sample for
      screening of suspected infected fish. On the basis of mortality, severity of
      lesions, and intensity and frequency of ISH signals, ISAV isolate Norway 810/9/99
      was the most virulent and U5575-1 the least virulent isolate studied.

PMID- 15872381
TI  - Assessment of cyclooxygenase-2 expression in canine hemangiosarcoma, histiocytic
      sarcoma, and mast cell tumor.
AB  - To determine whether cyclooxygenase-2 (COX-2) is expressed in canine
      hemangiosarcoma (HSA), histiocytic sarcoma (HS), and grade-II mast cell tumor
      (MCT), we performed immunohistochemistry using COX-2 antibodies in the
      aforementioned tumors. Twenty cases of each tumor type were selected initially
      from the Laboratory of Pathology archives of cases submitted through the Matthew
      J. Ryan Veterinary Hospital of the University of Pennsylvania.
      Immunohistochemistry was performed, using a polyclonal antiprostaglandin
      endoperoxide synthase immunoglobulin G COX-2 antibody. Sections from the kidneys
      of young dogs, in which the macula densa stains positive for COX-2, served as
      positive controls. Slides were reviewed by a single pathologist (M. H.
      Goldschmidt) and graded for COX-2 expression according to previously established
      scales. Descriptive data is given for each tumor type. COX-2 expression was
      identified in 0 of 19 HSA, 1 of 20 HS, and 1 of 17 grade-II MCT. Although COX-2
      has been shown to be overexpressed in selected human sarcomas and hematopoeitic
      tumors, these results indicate that canine HSA, HS, and MCT do not express COX-2
      in any appreciable fashion.

PMID- 15872382
TI  - Unilateral limb enlargement in a dog with a malignant peripheral nerve sheath
      tumor.
AB  - A 3- to 4-month-old female Golden Retriever dog presented with right hind limb
      enlargement. Physical examination of the limb and radiographic findings initially
      included soft tissue swelling with elongation, bowing, and cortical irregularity
      of the femur and tibia. During a period of approximately 7 months, pathology in
      the limb progressed to include tarsal laxity, muscle atrophy, avulsion of the
      gastrocnemius muscle, and luxation of the patella. During surgical intervention
      to shorten the limb and repair the patellar luxation, a large soft tissue cyst
      was identified along the caudal aspect of the femur and stifle. The limb was
      later amputated, and a final diagnosis of malignant peripheral nerve sheath (PNS)
      tumor of the sciatic nerve and surrounding soft tissues was made. The unilateral
      limb enlargement in this dog appears to have been because of the development and
      progression of a malignant PNS tumor. The presentation and associated pathologic
      changes in the limb are unusual for canine PNS tumor but have similarities with
      neurofibromatosis in the limbs of humans.

PMID- 15872383
TI  - Malignant seminoma with metastasis, Sertoli cell tumor, and pheochromocytoma in a
      spotted dolphin (Stenella frontalis) and malignant seminoma with metastasis in a
      bottlenose dolphin (Tursiops truncatus).
AB  - Seminoma with metastasis was diagnosed in a spotted dolphin (Stenella frontalis)
      and an Atlantic bottlenose dolphin (Tursiops truncatus). Sertoli cell tumor and
      pheochromocytoma were also diagnosed in the spotted dolphin. The spotted and
      bottlenose dolphins were adult males that stranded and died on the coasts of
      northwest Florida and southeast North Carolina, respectively. Neoplasia is
      infrequently reported in cetaceans. This is the first report of seminoma, Sertoli
      cell tumor, and pheochromocytoma in a dolphin, the first report of three distinct
      neoplasms in a dolphin, and one of the few reports of malignant neoplasia in
      dolphins.

PMID- 15872384
TI  - Lipid-rich carcinoma of the mammary gland in a cat.
AB  - A 1.5-year-old female, intact, clinically healthy cat presented for a
      subcutaneous mass of the ventral abdomen. Surgical excision and microscopic
      examination of the mass were performed. Histologically, this was a discrete,
      unencapsulated, multilobular, expansile mass, which compressed the surrounding
      normal mammary tissue. Lobules were composed of tubuloacinar structures formed by
      atypical round to polygonal cells, which contained foamy to microvacuolated
      cytoplasm and variably sized, intracytoplasmic, distinct vacuoles causing nuclear
      peripheralization. Neoplastic cells demonstrated intense and diffuse
      immunoreactivity for cytokeratin and lacked immunoreactivity for vimentin. The
      vacuolar contents stained positively with Oil RedO and negatively with periodic
      acid-Schiff and Alcian blue stains. Histomorphologic, histochemical, and
      immunohistochemial analysis support a diagnosis of lipid-rich mammary carcinoma.
      This is the first report of a cat with a lipid-rich variant of mammary carcinoma.

PMID- 15872385
TI  - KIT-positive gastrointestinal stromal tumor in a 22-year-old male chimpanzee (Pan
      troglodites).
AB  - Gastrointestinal stromal tumors (GIST), KIT-positive and KIT signaling driven or
      platelet-derived growth factor receptor alpha (PDGFRA) signaling driven
      mesenchymal tumors, are poorly known in nonhuman primates. Availability of KIT-
      and PDGFRA-inhibitor drug imatinib mesylate has greatly raised the interest for
      these tumors. At necropsy of a 22-year-old male chimpanzee, a round, firm 2-cm
      intramural tumor was incidentally found in the midbody of the stomach and
      diagnosed as a GIST. Histologically, the mass was composed of spindle to
      polygonal epithelioid cells arranged in short to intermediate-length, interlacing
      streams, bundles, and nodular whorls often separated by hyalinized eosinophilic
      matrix. The mitotic rate was a maximum 1/50 high-power field.
      Immunohistochemically, the tumor cells were diffusely positive for KIT and CD34,
      focally positive for alpha-smooth muscle actin, and negative for muscle specific
      actin, desmin, S-100 protein, synaptophysin, and glial fibrillary acidic protein.
      Because the majority of human GISTs have gain-of-function KIT or PDGFRA
      mutations, genomic sequences of KIT exons 9, 11, 13, and 17 and PDGFRA exons 12
      and 18 from this chimpanzee GIST were polymerase chain reaction amplified and
      sequenced. However, no mutation was identified in the analyzed "mutational hot
      spots." This study is the first extensive histomorphologic, immunohistochemical,
      and molecular genetic analysis of a chimpanzee GIST. More cases of nonhuman
      primate GISTs should be analyzed to discover the clinicopathologic spectrum of
      GISTs in these species.

PMID- 15872386
TI  - Low-grade glial tumor with features of astroblastoma in a dog.
AB  - A 12-year-old, neutered, male Belgian Malinois/Great Dane cross dog presented
      with a 5-month history of weakness and lack of endurance followed by acute onset
      of rear limb ataxia. At autopsy, a 9 x 16 mm, multilobular, firm, white to tan,
      expansile mass was found in the cerebellum. Mild dilatation of the lateral
      ventricles was also noted. Histologically, there was a well-demarcated glial
      neoplasm composed of medium-sized astrocytic elements that had homogeneous
      cytoplasm, sometimes with globular eosinophilic inclusions, irregular
      peripherally located nuclei with a single nucleolus, and short cytoplasmic
      processes. Prominent perivascular pseudorosettes with cellular processes in
      contact with blood vessels were present. Some blood vessels exhibited hyalinized
      walls. Mitotic figures were not observed. Immunohistochemically, neoplastic cells
      expressed glial fibrillary acidic protein and vimentin. These features are
      consistent with an astroblastoma. This is the first clinicopathologic correlation
      and detailed description of a low-grade glial tumor with features of
      astroblastoma in a dog.

PMID- 15872387
TI  - Pathology of bartonella endocarditis in six dogs.
AB  - In a 5-year retrospective study of dogs presenting to the Veterinary Medical
      Teaching Hospital at the University of California, Davis, there were 31
      histologic diagnoses of valvular endocarditis. By polymerase chain reaction (PCR)
      amplification of embedded valvular tissue, Bartonella organisms were exclusively
      associated with 6 out of 31 cases (19%). Confirmed Bartonella cases involved the
      aortic valve alone (five out of six) or in combination with the mitral valve (one
      of six). Microscopic features of Bartonella endocarditis were compared with
      valves from non-Bartonella endocarditis and with valvular change unrelated to
      infectious agents (endocardiosis). Features of Bartonella endocarditis included a
      combination of fibrosis, mineralization, endothelial proliferation, and
      neovascularization with variable inflammation. None of these features is
      specific; however, the combination is distinct both from endocarditis caused by
      culturable bacteria and from endocardiosis. Ultrastructural analyses revealed
      both extracellular and intraendothelial bacteria. Clinical history, serology, and
      PCR are currently necessary to establish an etiologic diagnosis of Bartonella
      endocarditis.

PMID- 15872388
TI  - Combined-type osteosarcoma in a rhesus macaque.
AB  - A femoral mass from a 15-year-old rhesus macaque was evaluated. Grossly, the mass
      consisted of a large, osteolytic focus in the distal femur, a gelatinous core of
      neoplastic tissue in the medullary cavity, and an invasive mass-obliterating
      musculature of the thigh. On histopathologic evaluation, three neoplastic
      mesenchymal cell populations, osteoblasts, fibroblasts, and primitive mesenchymal
      cells were identified. The mass was diagnosed as a combined type osteosarcoma. To
      our knowledge, this is the first osteosarcoma in a rhesus macaque with this
      subclassification.

PMID- 15872389
TI  - Cutaneous angiomatosis in a young dog.
AB  - A 1-year-old, spayed, female, mixed-breed dog had two reddish-purple cutaneous
      lesions, one on the right dorsal antebrachium and the other on the right
      shoulder. The lesions consisted of approximately 13 x 3 cm and 15 x 10 cm,
      irregular, patchy regions of 0.5-3.0 cm, circular, sometimes raised, reddish
      purple swellings resembling ecchymoses. The lesion on the antebrachium had been
      noticed since the dog was adopted at 6 months of age and appeared to have
      increased in size over an 11-week period, at which time skin punch biopsy
      revealed an infiltrative pattern of well-differentiated blood vessels leading to
      an interpretation that the lesion was a well-differentiated hemangiosarcoma. The
      second lesion was revealed when the dog had its fur shaved in that area during
      surgical preparation to excise the antebrachial lesion. No other skin lesions
      were found on the dog. Microscopically, there was a widely disseminated and
      infiltrative-like pattern of benign-appearing small blood vessels, which were
      throughout the superficial and deep dermis and subcutis. Although the
      disseminated nature suggested malignancy, the histologic appearance of well
      differentiated small blood vessels and nonprogressive clinical features indicate
      that the lesions were benign. The dog has been followed for 6 years and to date
      has no evidence of progression of the antebrachial lesion or shoulder lesion. To
      the authors' knowledge, this is the first report of a congenital angiomatosis
      like lesion in a young dog, with extensive involvement of the forelimb.

PMID- 15872390
TI  - Cell proliferation activity of proliferating bile duct after bile duct ligation
      in rats.
AB  - The cell proliferation activity of proliferating bile ducts produced by bile duct
      ligation (BDL) in rats was examined histologically, immunohistochemically, and
      ultrastructurally. Proliferating bile ducts, which were similar to normal bile
      ducts, increased with time after BDL. The cell proliferation activity of
      proliferating bile ducts, measured using proliferating-cell nuclear antigen and 5
      bromo-2'-deoxyuridine antibodies, tended to be high at 1 and 3 days after BDL and
      decreased progressively at 2 to 4 weeks after BDL. On the other hand, alpha
      smooth muscle actin-positive myofibroblast-like cells increased continuously
      after BDL. These findings indicate that there is a negative correlation between
      the cell proliferation activity of proliferating bile ducts and that of
      myofibroblast-like cells.

PMID- 15872391
TI  - Gastritis-associated adenocarcinoma and intestinal metaplasia in a Syrian hamster
      naturally infected with Helicobacter species.
AB  - The objective of this study was to evaluate stomachs of 2-year-old Syrian
      hamsters that were naturally colonized by multiple Helicobacter species including
      Helicobacter aurati. A previous report on 7- to 12-month-old Syrian hamsters
      described chronic gastritis and intestinal metaplasia, a putative preneoplastic
      lesion in the stomach, without cancer. This report describes an invasive
      adenocarcinoma at the pyloric-duodenal junction in one of nine hamsters at a site
      of helicobacter-associated inflammation and marked intestinal metaplasia. Ceca of
      nine of nine animals were culture positive and polymerase chain reaction positive
      for Helicobacter spp. Furthermore, immunohistochemical analysis of the stomach
      using a H. pylori polyclonal antibody detected positive-staining bacteria within
      the pyloric region of three of nine hamsters including the neoplastic glands.
      However, argyrophilic bacteria were demonstrated only within the stomach of the
      hamster with gastric adenocarcinoma. This is a first report of gastric
      adenocarcinoma in helicobacter-infected hamsters. Syrian hamsters appear suitable
      as potential model for studying development of helicobacter-associated gastric
      adenocarcinomas.

PMID- 15872392
TI  - Intestinal stromal tumors in a simian immunodeficiency virus-infected, simian
      retrovirus-2 negative rhesus macaque (Macaca mulatta).
AB  - Multifocal submucosal stromal tumors were diagnosed in a 5.5-year-old rhesus
      macaque (Macaca mulatta) experimentally infected with simian immunodeficiency
      virus, strain SIVsmE660, and CD4+ T cell depleted. The animal was negative for
      simian retroviruses, SRV-1, -2, and -5. Polymerase chain reaction analysis of DNA
      from tumor and spleen tissue revealed abundant, preferential presence of
      retroperitoneal fibromatosis herpesvirus, the macaque homologue of the Kaposi
      sarcoma-associated herpesvirus (human herpesvirus-8), in the tumors. This was
      corroborated by demonstration of viral latent nuclear antigen-1 in the nuclei of
      a majority of the spindeloid tumor cells. Low levels of an additional macaque
      herpesvirus, rhesus rhadinovirus, were also detected in the spleen and tumor
      tissues. The spindeloid cells labeled positively for vimentin and CD117 but were
      negative for CD31, CD68, desmin, and smooth muscle cell actin. Collectively,
      these findings suggest a relation to but not absolute identity with simian
      mesenchymoproliferative disorders (MPD) or typical gastrointestinal stromal
      tumors (GISTs).

PMID- 15872393
TI  - Orthopaedic trauma following tsunami: experience from Phang Nga, Thailand.

PMID- 15872394
TI  - Histomorphometric changes in the vessel wall at the site of amputation in
      diabetic patients--do they influence healing of the stump?
AB  - PURPOSE: To predict healing of the stump by assessing the microscopic vascular
      changes at the amputation site. METHODS: A cohort study was conducted on 39
      patients, 18 of them had below-knee amputation (group A) and 21 had ray
      amputation of a single toe (group B). Biopsies were taken from the anterior and
      posterior tibial arteries and the venae comitantes of group A patients. For group
      B patients, biopsies of the digital artery and dorsal vein of the toe were taken.
      RESULTS: In group A, 15 patients required no further amputation (group A1) and 3
      underwent a further above-knee amputation (group A2). In group B, 16 required no
      further amputation (group B1) and 5 underwent a below-knee amputation (group B2).
      Lumen narrowing caused by intimal thickening of the arteries was significantly
      different between groups A1 and A2 (p<0.05). Lumen narrowing of the dorsal veins
      between groups B1 and B2 was also significantly different (p<0.05). The
      proportion of the vessel walls made up of intima and media was significantly
      different in both A1 and A2 as well as B1 and B2 groups. The proportion of total
      wall thickness over the total diameter of the vessel was not significantly
      different between both subgroups of A and B. CONCLUSION: Intimal thickening and
      medial thinning in the arteries can be used to predict the stump healing in
      patients who underwent below-knee amputation. For ray amputation patients,
      similar changes occurred in the dorsal veins, and this finding can also be used
      to predict the healing of the stump. However, intimal thickening occurred at the
      expense of the media; therefore, there is little change in the wall thickness.

PMID- 15872395
TI  - Morphological studies on the ageing and osteoarthritis of the articular cartilage
      in C57 black mice.
AB  - PURPOSE: To study the cause and mechanism of joint degeneration in
      osteoarthritis, through histopathological and ultrastructural-histochemical
      experiments on the articular cartilage of the knees of the C57 black mouse.
      METHODS: 192 C57 black mice and a control group of 64 C57BL/6J mice were used in
      this study. The left and right knee articular capsules of the joints were removed
      and stained. Each articular cartilage sample was examined and osteoarthritic
      changes were assessed using a transmission electron microscope. The severity of
      osteoarthritis in the knee joint cartilage of C57 black mice was histologically
      assessed using a classification system described by Okabe, based on Maier's
      system. RESULTS: The incidence and the severity of osteoarthritis gradually
      increased with age; the incidence increased from 20% at 2 months to 80% at 16
      months. Irreversible changes appeared at an advanced stage, and the process of
      degeneration was quite similar to that in human osteoarthritis. Through
      transmission electron microscopy, we observed poorly developed Golgi apparatus,
      markedly increased intracellular microfilaments, decreased proteoglycan granules,
      and broken collagen networks in all stages of osteoarthritis. By contrast, Golgi
      apparatus and other organelles were well developed in histologically normal mice
      of all ages. Proteoglycan granules, which mainly consisted of keratan sulphate,
      were observed; collagen networks were maintained. CONCLUSION: Disturbed protein
      transport and sugar synthesis in chondrocytes, caused by the deficient
      development of the Golgi apparatus, could result in degenerative changes in
      articular cartilage. The structure and function of the matrix were maintained
      mainly because of the continued presence of keratan sulphate.

PMID- 15872396
TI  - Blood salvage in total hip and knee arthroplasty in a community hospital: a
      retrospective study.
AB  - PURPOSES: To assess the results of postoperative and intra-operative blood
      salvage in patients undergoing total knee and hip arthroplasty, respectively, and
      to determine if both methods of blood salvage reduce allogeneic transfusion.
      METHODS: Of 229 patients who attempted blood salvage, 114 of 152 patients who
      underwent total knee arthroplasty received the salvaged blood postoperatively, 35
      of 77 patients who underwent total hip arthroplasty received the salvaged blood
      intra-operatively. Various data were collected to assess whether certain factors
      resulted in autologous and/or allogeneic blood transfusions. RESULTS: Patients
      that received postoperative salvaged blood after total knee arthroplasty
      generally had higher postoperative levels of haemoglobin and haematocrit compared
      to those who did not. Patients with autologous blood transfusion following
      cemented knee surgery were less likely to require allogeneic blood transfusion.
      For hip arthroplasty patients, postoperative levels of haemoglobin and
      haematocrit were similar in both groups who received and did not receive salvaged
      blood. Lower preoperative haemoglobin and haematocrit levels correlated with a
      greater likelihood of autologous and/or allogeneic blood transfusion for both
      knee and hip arthroplasty patients. CONCLUSIONS: Although total knee arthroplasty
      patients who received salvaged blood had higher haemoglobin levels on the first
      postoperative day, the receipt of salvaged blood did not significantly reduce the
      incidence of allogeneic blood transfusion, because salvaged blood was a kind of
      blood loss. However, reinfusion of salvaged blood may reduce the number of units
      of allogeneic blood used. Given the short supply of allogeneic blood and its
      risks of transmitting disease, intra-operative and postoperative blood salvage
      carries clear advantages.

PMID- 15872397
TI  - Modified calcaneal index: a new screening tool for osteoporosis based on plain
      radiographs of the calcaneum.
AB  - PURPOSES: To assess osteoporosis using plain radiography of the calcaneum by
      studying the performance characteristics of the modified calcaneal index through
      inter- and intra-observer agreement. To study the correlation of the modified
      calcaneal index to quantitative ultrasound of the calcaneus and bone mineral
      density (BMD) of the femoral neck and distal radius. METHODS: Lateral calcaneal
      radiographs of 252 women who participated in a clinical trial for osteoporosis
      were reviewed. The BMD of the hip and distal radius was measured and the calcanea
      were assessed using ultrasound. The calcaneal radiographs were graded by 3
      clinicians according to a previously described 5-grade calcaneal index. A
      modified 3-grade calcaneal index was then developed. RESULTS: The highest scores
      of intra- and inter-observer reliability of the modified calcaneal index were
      0.45 and 0.40, respectively, which were higher than those of the 5-grade
      calcaneal index. The correlation of the modified calcaneal index with other
      measures was significant (hip BMD, r=0.31; distal radius BMD, r=0.28; calcaneal
      speed of sound, r=0.20; broadband ultrasound attenuation, r=0.36) [p<0.005].
      There were significant differences in hip BMD, distal radial BMD, calcaneal speed
      of sound, and broadband ultrasound attenuation between the 3 grades of the
      modified calcaneal index (Kruskal-Wallis 1-way ANOVA; p<0.0001). CONCLUSION: The
      modified calcaneal index can be used to measure bone structure and skeletal
      strength and is a suitable screening tool for osteoporosis in places where
      advanced approaches to bone-status assessment are not available.

PMID- 15872398
TI  - The need for multidisciplinary management of patients with upper thoracic spine
      fractures caused by high-velocity impact: a review of 32 surgically stabilised
      cases.
AB  - PURPOSE: To analyse the characteristics of patients who underwent surgery for
      fractures of the upper thoracic spine (T1-T6) in our institution. The thoracic
      spine is supported by the rib cage and associated ligaments; therefore,
      displacement and fracture of the upper thoracic spine in healthy young adults
      require a great force. The relatively narrow spinal canal around the spinal cord
      in this area could result in severe neurological deficit should fractures occur.
      METHODS: The treatment course of 32 patients (26 men and 6 women) who underwent
      surgery for fractures of the upper thoracic spine between February 1995 and March
      2001 was retrospectively reviewed. Parameters of injuries and treatment methods
      were evaluated. RESULTS: Of the 32 patients, 29 were injured in traffic accidents
      (15 motorcycle and 14 vehicle), 2 in falls, and one by a heavy door falling on
      his back. 29 patients had spinal fractures at more than one level. 23 patients
      had complete, 7 had incomplete, and 2 had no neurological deficit. 30 patients
      required multiple modalities of radiological imaging (in addition to plain
      radiography) for diagnosis. 20 patients sustained other injuries apart from
      spinal fractures, 15 of them had associated chest injuries. CONCLUSION: High
      velocity fractures of the upper thoracic spine are injuries with devastating
      consequences, and can result in severe neurological deficit and concomitant
      injuries. These patients are best treated by a multidisciplinary approach.

PMID- 15872399
TI  - Microvascular density of rapidly destructive arthropathy of the hip joint.
AB  - PURPOSE: To assess the vascularity of the femoral head and determine how it is
      related to the destruction of the arthritic hip joint. The process of destructive
      arthropathy in arthritic hip joints is variable. Some patients with
      osteoarthritis of the hip have rapidly progressive destructive changes resulting
      in the disappearance of the femoral head. METHOD: Six femoral heads from patients
      diagnosed with rapidly destructive arthropathy and 6 femoral heads from patients
      with secondary osteoarthritis caused by acetabular dysplasia were analysed to
      reveal the association between blood capillaries and osteoclasts. The von
      Willebrand Factor immunostaining and counterstaining with Mayer's haematoxylin
      were used to label the microvessels and osteoclasts in formalin-fixed, paraffin
      embedded specimens of femoral heads. The numbers of immunostained microvessels
      and osteoclasts in selected regions were counted. RESULT: The microvascular
      density of the bone surfaces of rapidly progressive arthritic hips was
      hypervascular. Osteoclasts were also found in increased numbers on the bone
      surfaces of rapidly progressive arthritic hips. The higher microvascular density
      coincided with extensive bone destruction and with the increased osteoclast
      count. CONCLUSION: These findings suggested that hypervascularity of the
      granulation in the femoral head may be associated with bone and joint
      destruction.

PMID- 15872400
TI  - Does the self-centering mechanism of bipolar hip endoprosthesis really work in
      vivo?
AB  - PURPOSES: To examine radiographically the component motion in a bipolar
      prosthesis and to determine whether the self-centering mechanism really works in
      vivo. METHODS: 38 patients with 41 bipolar hip endoprostheses (30 for
      coxarthrosis and 11 for osteonecrosis of femoral head) were included in this
      study. Two radiographs of each case were taken to evaluate the self-centering
      mechanism. The first anteroposterior radiograph of both hip joints was taken at
      the maximum abduction while the patient standing on the endoprosthetic leg. The
      second radiograph was taken after the patient returned to neutral position while
      standing on 2 legs. In the present study, the order in which the radiographs were
      taken differed from previously reported studies. The radiographs were analysed
      using the method similar to that of Drinker and Murray. The adductive motion from
      abduction to a neutral position is within the range of inner bearing oscillation.
      RESULTS: The outer head alignment changed from 23 degrees to 12 degrees in the
      patients with osteonecrosis. However, the valgus position of the outer head (36
      degrees) remained unchanged in the patients with coxarthrosis standing on 2 legs
      in the neutral position. CONCLUSION: The self-centering mechanism of the bipolar
      endoprosthesis functioned in the patients with osteonecrosis, but did not work in
      the coxarthrosis group.

PMID- 15872401
TI  - Debridement and continuous irrigation for the treatment of pyogenic arthritis
      caused by the use of intra-articular injection in the osteoarthritic knee:
      indications and outcomes.
AB  - PURPOSE: To discuss the indications and therapeutic outcomes of synovectomy,
      debridement, and continuous irrigation for the treatment of pyogenic arthritis
      caused by intra-articular injection used in the treatment of osteoarthritis of
      the knee. METHODS: Records of 41 patients with infectious arthritis of the knee
      who presented to our hospital from 1981 were reviewed. 11 of them had a history
      of intra-articular injection. They underwent synovectomy, debridement, and
      continuous irrigation using a Salem double-lumen tube after confirmation that one
      side of the femorotibial joint cartilage was basically healthy. RESULTS: The
      infection was successfully treated in 9 of the 11 patients. Of these 9 patients,
      one died after 3 years and 2 underwent total knee arthroplasty after 3 and 8
      years. The remaining 6 patients were followed up for 5 to 15 years. Five of them
      had deteriorating arthropathy, and the condition was unchanged in the others. Two
      of these 6 patients had pain while walking, and their Japanese Orthopaedic
      Association scores were 70. The remaining 4 had good knee function and reduction
      of pain, with a mean Japanese Orthopaedic Association score of 91 and a mean
      range of motion of 131 degrees. CONCLUSION: Arthrodesis is frequently considered
      the treatment for osteoarthritis if the joint destruction has affected the weight
      bearing surface. However, in our experience, even when inflammatory granulation
      develops in the cartilage surface of one side of the femorotibial joint, good
      results can still be obtained by synovectomy, debridement, and continuous
      irrigation. After the pyogenic arthritis has subsided, if osteoarthritis has
      advanced and bowleg has exacerbated, further treatment options are available,
      such as tibial resection and even joint replacement. Continuous irrigation should
      be considered a feasible treatment option for pyogenic arthritis.

PMID- 15872402
TI  - Reconstructive treatment following resection of high-grade soft-tissue sarcomas
      of the lower limb.
AB  - PURPOSE: To review the role of free tissue transfer in reconstructive surgery
      following resection of high-grade soft-tissue sarcomas of the lower limb.
      METHODS: Medical records of all consecutive patients with high-grade soft-tissue
      sarcomas of the lower limbs between August 1997 and September 2003 were reviewed.
      RESULTS: Of 8 patients (6 women and 2 men) aged between 19 and 65 years, 4 had
      malignant fibrous histiocytoma, one had malignant peripheral nerve sheath tumour,
      one had synovial sarcoma, one had recurrent liposarcoma, and one had epitheloid
      sarcoma. The tumour sizes ranged from 132 cm(2) to 483 cm(2). The soft-tissue
      defects following tumour extirpation ranged from 153 cm(2) to 896 cm(2). The
      flaps used were 3 free latissimus dorsi flaps, 2 free osteoseptocutaneous fibula
      flaps (one vascularised fibula flap and one 'double barrel' fibula flap), one
      free rectus abdominis flap, 2 free mini-transverse rectus abdominis flaps, and
      one pedicled rectus abdominis flap. Five patients did not have local recurrence
      and systemic metastases. CONCLUSION: Tissue transfer allows early adjuvant
      therapy facilitating the multimodal approach for the high-grade soft-tissue
      sarcomas of the lower extremity.

PMID- 15872403
TI  - Capsulolabral augmentation by blood injection increases the intrinsic stability
      provided by the glenoid.
AB  - PURPOSE: To test the hypothesis that the intrinsic stability of the cadaveric
      glenoid can be augmented by the injection of blood into the labrum. METHODS: The
      intrinsic stability of 10 fresh frozen cadaveric glenoids was assessed by
      measuring the balance stability angle. Pretreatment values of 8 directions in
      each glenoid were obtained. The labrum was then injected with blood freshly drawn
      from a volunteer. After the injected blood clotted, measurements of the balance
      stability angle of the 8 directions were again obtained. RESULTS: The mean pre
      injection balance stability angle for 7 of the 8 directions were significantly
      increased by the injection of blood: anterosuperior, from 25 to 35 degrees
      (p<0.005); anterior, from 27 to 34 degrees (p<0.01); anteroinferior, from 36 to
      39 degrees (p<0.005); inferior, from 38 to 41 degrees (p<0.02); posteroinferior,
      from 35 to 42 degrees (p<0.01); posterior, from 27 to 35 degrees (p<0.0005); and
      posterosuperior, from 26 to 29 degrees (p<0.005). Cross-sections of injected
      labra demonstrated a firm clot within the labrum with substantial increases in
      thickness. CONCLUSION: The intrinsic stability of cadaveric glenoids can be
      significantly augmented by the injection of blood into the labrum. It is possible
      that blood injection may be a useful primary or adjunct procedure in the open or
      arthroscopic management of glenohumeral instability.

PMID- 15872404
TI  - Femoral neck fractures complicating metal-on-metal resurfaced hips: a report of 2
      cases.
AB  - Metal-on-metal hip resurfacing arthroplasty is increasingly popular for younger
      patients with advanced hip disease. Intra-operative or immediate postoperative
      femoral neck fracture after metal-on-metal hip resurfacing is a well-described
      technical complication, ranging from 0% to 1.5%. We report 2 cases of late
      femoral neck fracture occurring 8 and 15 months following the index operation,
      with a review of the literature. We recommend that patient selection should be of
      prime importance before embarking on metal-on-metal surface hip replacement to
      avoid such complications.

PMID- 15872405
TI  - Dislocation of a polished femoral stem following a cemented total hip
      arthroplasty: a report of 2 cases.
AB  - We report 2 cases of hip dislocation after a total hip arthroplasty, which could
      not be successfully reduced by closed method. Post-manipulation radiographs
      revealed proximal migration of the prosthesis in both cases, which required open
      reduction. The pathogenesis and treatment of this hip dislocation is discussed.

PMID- 15872406
TI  - Knee dislocation of a morbidly obese patient: a case report.
AB  - Knee dislocations of morbidly obese patients after a trivial fall are not
      uncommon. We report a case of closed reduction for a dislocated right knee of a
      26-year-old obese woman. After closed reduction under general anaesthesia, her
      knee was supported by pillows in 30 degrees flexion. No external splint was used
      because of the enormous size of the leg. At day 4 after reduction, the patient
      had numbness over the dorsum of the right foot and was unable to dorsiflex. She
      was diagnosed as having peroneal nerve palsy and was fitted with a foot drop
      splint. One week after reduction, she started active, assisted knee mobilisation
      and tip-toe weight bearing. At 24 months after reduction, the patient was able to
      walk unaided and had 100 degrees of knee flexion. She had a good foot function
      and a grade II in the Lachman's test, with no varus or valgus instability. This
      case highlights the importance of early mobilisation, which can result in good
      outcome even without operative treatment.

PMID- 15872407
TI  - Dysplasia epiphysealis hemimelica of the talus: two case reports.
AB  - Trevor's disease, also known as dysplasia epiphysealis hemimelica, is an uncommon
      skeletal developmental disorder representing an osteochondroma occurring in one
      or more epiphyses. We present 2 cases of dysplasia epiphysealis hemimelica in an
      8-year-old female and a 12-year-old male who suffered from a hard swelling of the
      ankle joint. The female patient was treated by surgical excision and the male
      patient conservatively.

PMID- 15872408
TI  - Benign fibrous histiocytoma of the distal radius with congenital dislocation of
      the radial head: a case report.
AB  - Benign fibrous histiocytoma is such a rare tumour that only a few cases have been
      reported in the literature. A patient with an apparently benign lesion of the
      distal radius, along with congenital dislocation of the radial head, was
      presented at St. John's Medical College Hospital in Bangalore, India. Pain was
      the chief symptom. There were histological features of non-ossifying fibroma in
      the lesion. Because of its unusual radiological appearance and atypical clinical
      course, the lesion was diagnosed as fibrous histiocytoma. In this case report, we
      review similar cases in the literature and discuss an unusual association with
      congenital dislocation of the radial head.

PMID- 15872409
TI  - Delayed diagnosis of Ewing's sarcoma of the right humerus initially treated as
      chronic osteomyelitis: a case report.
AB  - We report a case of limited stage Ewing's sarcoma which was initially treated as
      chronic osteomyelitis for 3 years. A 24-year-old man presented with a one-week
      history of pain in the right arm and fever, with histology suggestive of
      osteomyelitis of the affected humerus. He developed multiple relapses of pain and
      fever; each episode responded to antibiotic treatment. A second biopsy was
      performed 3 years later and confirmed a diagnosis of Ewing's sarcoma. Despite a 3
      year delay in diagnosis, the disease remained localised. This case report
      highlights an atypical facet of the natural history of Ewing's sarcoma: a
      response to antibiotic and anti-inflammatory agents, and the limited stage of the
      disease despite a misdiagnosis of 3 years. This suggests the possibility that
      anti-inflammatory agents exert an inhibitory effect on the tumour growth. We also
      highlight the newer histologic and immunologic staining used in the diagnosis of
      Ewing's sarcoma.

PMID- 15872410
TI  - Perforated appendicitis causing thigh emphysema: a case report.
AB  - We report a case of thigh emphysema resulting from perforated appendicitis. The
      patient was an 83-year-old man who had no apparent abdominal signs and was
      initially misdiagnosed as having psoas abscess. Magnetic resonance imaging of the
      pelvis revealed appendicitis, and a barium enema showed a leakage of enhanced
      contrast material from the appendix region down into the thigh. A retroperitoneal
      perforation of the retrocaecal appendix without peritonitis was diagnosed. The
      patient underwent an appendectomy and curettage of the retroperitoneal and psoas
      muscle spaces, as well as the thigh. He recovered gradually, though the abscess
      had extended into the hip joint and resulted in osteomyelitis, requiring an
      additional procedure of resection arthroplasty. The patient fully recovered with
      no signs of infection one year postoperatively.

PMID- 15872411
TI  - Cemented or uncemented femoral component in primary total hip replacement? A
      review from a clinical and radiological perspective.
AB  - Controversy exists regarding the optimal method of fixation for primary total hip
      replacement, particularly the femoral component. We performed a systematic
      literature review to explore whether cemented total hip replacement can achieve
      better clinical and radiological outcomes. A total of 29 publications were
      selected using computer-aided and manual searches. A qualitative comparison of
      results in clinical and radiological changes was then conducted. Most of the
      literature showed that better short-term clinical and functional outcomes could
      be obtained from cemented femoral fixation than from uncemented femoral fixation.
      Results were less clear for the mid-term clinical outcome, though in general,
      cemented fixation still appeared to show a superior clinical outcome.
      Radiographic differences are variable and do not seem to correlate with clinical
      findings. For the short- and mid-term, cemented femoral component is recommended.
      However, a long-term randomised trial combined with a large cohort study or
      registry is needed.

PMID- 15874809
TI  - Hyperpyrexia among infants younger than 3 months.
AB  - OBJECTIVE: To determine the prevalence of serious bacterial infection in infants
      younger than 3 months with fever > or =40 degrees C. METHODS: We retrospectively
      identified all infants younger than 3 months with fever who presented to a
      pediatric emergency department. The medical records were reviewed. The prevalence
      of serious bacterial infection (SBI) among those patients with hyperpyrexia was
      compared with febrile infants with lower fever. RESULTS: 5279 infants younger
      than 3 months with fever were reviewed. Ninety-eight patients (1.7%) had triage
      temperature > or =40 degrees C rectally. Median age, temperature, and white blood
      count for those with hyperpyrexia were 58 days (interquartile range [IQR] 36-78
      days), 40.2 degrees C (IQR, 40.0-40.4 degrees C), and 10,800/mm3 (IQR, 7900
      14,600/mm3), respectively. Diagnostic studies included blood culture (100%),
      urine culture (100%), lumbar puncture (100%), chest radiographs (34%), and stool
      cultures (11%). SBI was found in 38% infants with hyperpyrexia: urinary tract
      infection was the most common SBI (71%). Among patients with hyperpyrexia,
      patients with SBI had similar mean white blood cell counts (14,000 vs. 10,200
      cells/mm3) and age (54 vs. 53 days) as those with hyperpyrexia but no SBI. The
      prevalence of SBI among febrile infants with temperatures > or =40.0 degrees C
      was 38% (95% CI 27-48%) compared with those with fever < or =40 degrees C: 8.8%
      (95% CI 8.1-9.5%). CONCLUSION: Hyperpyrexia is rare among febrile infants younger
      than 3 months. One-third of infants with temperature > or =40.0 degrees C had
      SBI. Future management algorithms might include hyperpyrexia as a risk factor for
      serious infection.

PMID- 15874810
TI  - Sedation for pediatric CT scanning: is radiology becoming a drug-free zone?
AB  - INTRODUCTION: Cooperation for a diagnostic study is a frequent indication for
      pediatric procedural sedation. This study examines the continued need for
      sedation in the era of fast helical computerized tomography (CT) scanners.
      METHODS: Medical records of children younger than 72 months undergoing CT scans
      were systematically reviewed to identify the use of procedural sedation to
      complete their diagnostic studies. Statistical analysis was through ANOVA and
      regression modeling. RESULTS: A total of 104 patients underwent 122 CT studies.
      Requests originated from 3 sources: 59.8% ED (n = 73), 38.5% Neonatal Intensive
      Care Unit (n = 47), and 1.6% Pediatric Ward (n = 2). Studies performed included:
      79.5% head/facial (n = 97), 15.6% abdomen/pelvis (n = 19), and 5.9% other (n =
      6). The mean ages of all study patients was 23.4 (+/-2.4) months with a median of
      14 months. Only 8.6% patients (n = 9) received any sedation. The mean age of
      sedated patients was 18.8 (+/-2.7) months with a median of 21 months. With the
      exception of one 4-month-old, all other sedated children were between 12 and 30
      months. Sedative use occurred in 36.4% of patients in this age group, which was
      significantly greater than the remainder of the study group (OR 56.5, 95% CI 9
      1091, P < 0.001) Sedative agents used included: diphenhydramine (4),
      pentobarbital (1), propofol (1), ketamine (1), midazolam (1),
      diphenhydramine/pentobarbital (1). CONCLUSIONS: Procedural sedation is
      infrequently used in infants and young children undergoing helical CT studies.

PMID- 15874811
TI  - Factors affecting emergency department assessment and management of pain in
      children.
AB  - OBJECTIVE: To evaluate statewide emergency department assessment and management
      of pain in pediatric patients as a quality improvement initiative. METHODS: 2002
      Survey of Illinois Hospital emergency department's pediatric pain assessment and
      management strategies, in conjunction with a retrospective chart review of
      children, ages 0 to 15 years, treated for an extremity fracture. Survey results
      were available for 123 (59.4%) hospitals; 933 charts (107 hospitals) were
      reviewed for pain management. Survey results were compared with practices
      identified by chart review. RESULTS: Use of a pain assessment scale estimated by
      the survey was 92%, compared with 59% use by chart review. Use of pain assessment
      scales for infants was limited. Fifty percent of patients in moderate to severe
      pain would be offered an analgesic. Six- to 15-year-old children would be offered
      opioids more often than children aged 0 to 1 and 2 to 5 years. Offering higher
      potency narcotic analgesics was associated with patient's age, geographic
      location of the facility, and emergency department volume. Providing an analgesic
      (odds ratio 4.53, 95% confidence interval 2.89-7.10), offering supportive care
      (odds ratio 2.37, 95% confidence interval 1.44-3.89), and pediatric-focused
      annual nurse competencies (odds ratio 1.90, 95% confidence interval 1.18-3.06)
      correlated with reduction of the patient's pain. CONCLUSIONS: Disparity exists
      between perceived and documented emergency department pain management practices
      for children. Quality improvement initiatives should focus on improving pain
      assessment in infants, treating moderate to severe pain in children of all age
      groups, and education of health care providers in pain management strategies.
      Resources should target health care processes effective in decreasing pediatric
      pain.

PMID- 15874812
TI  - Do major televised events affect pediatric emergency department attendances or
      delay presentation of surgical conditions?
AB  - OBJECTIVE: To investigate whether major televised sporting events influence the
      level of attendance at a pediatric emergency department or reduce subsequent
      surgical admissions. METHODS: A retrospective analysis of the number of emergency
      department attendances and subsequent surgical admissions on nights of televised
      Champions League soccer games, a major pan-European soccer tournament, was made.
      These figures were compared with paired nights with no live soccer television
      broadcast. RESULTS: In total, 2560 children and their care providers attended the
      emergency department between 5 PM on nights of televised Champions League soccer
      games and 9 AM the next morning (mean 40.0 per night, standard deviation 6.3).
      Out of these children, only 85 were subsequently admitted to the pediatric
      surgical department (mean 1.3 per night, standard deviation 1.1). There was no
      significant difference between these figures and the levels of attendance or
      admission on paired nights without a live broadcast. CONCLUSIONS: We have
      demonstrated that the live broadcast of soccer games from a major sporting
      tournament does not significantly decrease emergency department workload. In
      addition, it does not reduce the number of children who require admission to a
      pediatric surgical department. This suggests that the staffing organization of a
      pediatric emergency department cannot be altered on the basis that a major
      sporting tournament is being televised.

PMID- 15874813
TI  - Idiopathic thrombocytopenic purpura complicated by an intracranial hemorrhage
      secondary to an arteriovenous malformation.
AB  - OBJECTIVE: To report a case of idiopathic thrombocytopenic purpura (ITP)
      complicated by an intracranial hemorrhage (ICH) in a child with a previously
      undiagnosed arteriovenous malformation. CASE: We describe a child with known ITP
      who developed a severe headache, was evaluated in an emergency department of a
      community hospital, and was found by computer tomography (CT) scan to have an
      ICH. Despite treatment with platelets, corticosteroids, and intravenous
      immunoglobulin, she subsequently developed an acute change in mental status. A
      second CT scan showed that the hemorrhage had significantly increased in size
      despite treatment. The patient underwent an emergent splenectomy prior to a
      craniotomy to remove the hemorrhage. At the time of surgery, it was discovered
      that she had an arteriovenous malformation at the sight of the hemorrhage. Her
      recovery was unremarkable and she was discharged to home with no neurologic
      sequelae. CONCLUSIONS: ICH is a rare but life-threatening complication of ITP.
      Neurologic symptoms in a child with ITP should be quickly evaluated by CT scan.
      Most experts suggest careful observation for most cases of ITP. However, when
      neurologic symptoms occur, more aggressive treatment options must be used. Care
      of this child included an emergency splenectomy prior to her craniotomy.
      Pediatric emergency medicine practitioners must be aware of these neurologic
      symptoms and must not hesitate to involve pediatric surgeons and neurosurgeons in
      the care of the child. Prompt recognition and early intervention are the keys to
      improving outcomes when ICH complicates ITP.

PMID- 15874814
TI  - The protean manifestations of blunt cardiac trauma in children.
AB  - We present a case series of pediatric blunt cardiac trauma with a variety of
      cardiac abnormalities, occurring immediately and after the initial insult. The
      range of complications and importance of serial evaluations are emphasized.

PMID- 15874815
TI  - The lost endotracheal tube: an unreported complication of prehospital intubation.
AB  - This case describes a previously unreported rare, but potentially disastrous,
      complication of endotracheal tube intubation initiated by prehospital emergency
      medical services personnel. This report details an inadvertent prehospital
      esophageal intubation and a critical error in communication between the
      prehospital and hospital service that resulted in failure to identify or remove
      the tube until after admission. The discussion includes complications of
      endotracheal tube intubation and esophageal foreign bodies. Proper communication
      between medical personnel is essential to reduce medical errors. Refraining from
      the use of slang terms may help prevent miscommunication between personnel upon
      transfer of patient care. This case shows the need be critical, observant, and
      wary at all times for even the most implausible findings in medicine.

PMID- 15874817
TI  - Posterior sternoclavicular joint dislocation in children-role of spiral computed
      tomography.
AB  - Traumatic posterior dislocation of the sternoclavicular joint is an uncommon
      injury in children. It is not normally well seen on plain films. We report 2
      cases where spiral computed tomography with intravenous contrast confirmed the
      clinical suspicion of sternoclavicular joint dislocation and also allowed
      assessment of the adjacent mediastinum for possible complications. Emergency
      physicians should be aware that the use of spiral computed tomography is the
      procedure of choice in posterior sternoclavicular joint dislocation. This is
      particularly helpful in allowing multiplanar reconstruction to show complications
      arising in the mediastinum.

PMID- 15874816
TI  - Renovascular hypertension in infant presenting with cardiogenic shock.
AB  - A 35-day-old infant admitted with cardiogenic shock was hypertensive shortly
      after initial resuscitation therapy. The hypertension did not respond to
      increasing doses of sodium nitroprusside. An abnormal blood flow in the right
      renal artery was detected by pulsed Doppler ultrasonography, and a prompt blood
      pressure response to oral captopril suggested a diagnosis of renovascular
      disease. Renal angiography showed right main renal artery stenosis, abnormal
      intrarenal arteries, and nonfunctional right kidney; the patient subsequently
      underwent right nephrectomy with good effect. Myocardial dysfunction resolved 2
      months after control of the blood pressure.

PMID- 15874818
TI  - End-tidal carbon dioxide monitoring in pediatric emergencies.
AB  - End-tidal carbon dioxide (CO2) monitoring is useful in the prehospital setting,
      emergency department, intensive care unit, and operating room. Capnography
      provides valuable, timely information about the function of both the
      cardiovascular and respiratory systems. End-tidal CO2 monitoring is the single
      most useful method in confirming endotracheal tube position. It also provides
      information about dead space, cardiac output, and airway resistance. A thorough
      understanding of cardiopulmonary physiology and the technical nuances of
      capnometry is required for its optimal use in children. This review examines the
      basic physiology pertinent to end-tidal CO2 monitoring, its clinical
      applications, and evidence supporting its use in infants and children.

PMID- 15874820
TI  - Abnormal gait in a child with fever: diagnosing septic arthritis of the hip.
AB  - The diagnosis of septic arthritis should be considered in all children with hip
      pain. We review the evaluation of children who present with fever and hip pain,
      emphasizing features that may assist in distinguishing septic arthritis of the
      hip from transient synovitis. We also discuss the impact of the increased
      prevalence of methicillin-resistant Staphylococcus aureus on the management of
      septic arthritis of the hip.

PMID- 15874821
TI  - Self-reported pain intensity and associated distress in children aged 4-18 years
      on admission, discharge, and one-week follow up to emergency department.
AB  - OBJECTIVES: Pain is the most common complaint among children presenting to the
      Emergency Department (ED), yet it is poorly managed. Although the poor management
      of pain has been documented, no studies have simultaneously determined the
      distress caused by the presenting pain nor have children been followed after the
      ED visit to determine whether the pain and distress have resolved. The purpose of
      this study was to describe pain intensity, distress from pain, and treatment of
      pain in children presenting to the ED and to follow them 1 week later to describe
      resolution of their pain. METHODS: A survey design with follow up of patients
      identified with pain in 2 urban university-affiliated pediatric EDs with children
      between ages 4 and 18 (N = 533). Measures used included the Coloured Analogue
      Scale (CAS) for both pain and distress related to pain, mobility problems related
      to pain, and interference with activities of daily living due to pain. Chart
      reviews were conducted for documentation of pain assessment and analgesic
      administration and prescription at discharge. RESULTS: Half of the children
      presenting were experiencing pain due to musculoskeletal injury and two-thirds of
      the pain problems had an onset within 48 hours of presentation to the ED. Mean
      pain intensity on admission was 5.2 (SD 2.3) and at discharge was 4.1 (SD 2.7),
      however, 22% had worsening of pain and for 26%, the pain remained the same. On
      admission, 12.8% reported pain intensity 8/10 or more but 23% reported distress
      levels 8/10 or more. Only 39% received analgesics during the visit and 11% were
      given a prescription for analgesics at discharge. Children (n = 104) were reached
      1 week following discharge from ED and only 5% were reporting pain of 4/10 or
      more but, of those reporting any pain at all, 34% reported distress from their
      pain of 4/10 or more. CONCLUSIONS: A greater proportion of children report high
      intensity of distress from pain than of pain intensity itself when in the ED.
      Only a small proportion of children received analgesics during the visit to the
      ED and only slightly more on discharge. Although pain seems to resolve by 1 week,
      distress is less likely to have resolved. More attention needs to be paid both to
      pain children are experiencing in the ED and equally to the accompanying
      distress.

PMID- 15874822
TI  - Fell off a swivel chair 3 days ago: my arm still hurts.

PMID- 15874823
TI  - ECGs in the ED.

PMID- 15874824
TI  - Pediatric emergency medicine: legal briefs.

PMID- 15874825
TI  - Pediatric emergency medicine fellowships adopt a new application process.
AB  - The growth of the subspecialty of pediatric emergency medicine has created a
      subsequent growth in the demands of pediatric emergency medicine fellowship
      training. To facilitate the application process for both applicants and
      fellowship training programs, a uniform application and uniform deadlines have
      been adopted by the Pediatric Emergency Medicine Fellowship Director's
      Subcommittee. The Electronic Residency Application Service will provide online
      support necessary for the implementation of this new process. A description of
      the new process and a description of theoretical benefits from this change are
      described. Pediatric emergency medicine fellowship applicants should be
      encouraged to investigate resources describing the new application process.

PMID- 15874828
TI  - The International Federation for Cervical Pathology and Colposcopy (IFCPC).

PMID- 15874829
TI  - Cervical cancer screening: will human papillomavirus testing replace cytology?

PMID- 15874830
TI  - Electrofulguration for low-grade squamous intraepithelial lesions of the cervix
      (CIN 1).
AB  - OBJECTIVES: To evaluate the therapeutic efficacy and adverse events of
      electrofulguration for the treatment of cervical intraepithelial lesion grade 1
      (CIN 1). MATERIALS AND METHODS: Women aged 19 years and older received
      electrofulguration for histologically proven exocervical CIN 1. They were
      followed up at 3, 6, and 12 months with cytologic analysis, colposcopy, and, when
      indicated, histologic examination. Therapeutic success was defined as absence of
      disease at 12 months after therapy. Adverse effects were recorded during and
      after the procedure. RESULTS: Of 78 women treated, 32 (41.0%) were lost to follow
      up and 6 patients (7.7%) were retreated. Using intent-to-treat definition
      including patients lost to follow-up, 40 of 78 (52.6%) were free of disease at
      the 1-year follow-up visit. Excluding patients lost to follow-up, cure rates were
      87% (40/46) and 100% (40/40) after single and repeat treatment, respectively.
      Adverse effects included mild to moderate discomfort (78%), intermittent spotting
      (70%), and pelvic pain (44%). The procedure lasted 2 minutes in 83% of cases and
      was easy to perform. CONCLUSIONS: Electrofulguration under local anesthesia is an
      attractive ablative treatment method for exocervical CIN 1 and compares favorably
      with cryocoagulation as per review of the literature.

PMID- 15874831
TI  - Direct visual inspection of the cervix for the detection of premalignant lesions.
AB  - OBJECTIVE: To assess the feasibility and performance of direct visual inspection
      (DVI) of the cervix as a primary tool for the detection of premalignant lesions
      of the cervix (HPV/CIN 1 and CIN 2,3). SETTING: The early cancer detection unit
      at the Ain Shams University Maternity Hospital in Cairo, Egypt. SUBJECTS AND
      METHODS: The study included 2049 women. Cervical smears were obtained from all
      women for cytologic evaluation followed by direct visual inspection (DVI) of the
      cervix after painting with 5% acetic acid. Women whose smear reports showed
      abnormal cells suggestive of squamous intraepithelial lesion (SIL) or human
      papillomavirus (HPV) infection or those who showed abnormalities or acetowhite
      areas on direct visual inspection subsequently were referred for colposcopy and
      biopsy when appropriate. Colposcopy also was performed for women with negative
      DVI and negative smears if they had contact bleeding or chronic per vaginal
      discharge. RESULTS: Mean (SD) age of women included in the study was 39.9 (10.2)
      years with their mean (SD) parity 2.9 (1.1). Results of DVI were normal in 1916
      women (93.4%) and showed abnormal acetowhite appearance in 133 (6.6%) women.
      There were 458 (22.4%) colposcopic examinations and 130 biopsies (6.34%) were
      carried out, picking up 83 cases of premalignant lesions (4.0%). Premalignant
      lesions were 80 HPV/CIN 1 and CIN 2,3. Direct visual inspection detected 71 of
      the 83 premalignant lesions (sensitivity, 85.5%; specificity, 96.8%; positive
      predictive value, 52.6%). Direct visual inspection missed one of the three
      samples showing CIN 2,3. Cervical cytologic analysis showed abnormal cells in 60
      (2.9%) and identified only 14 of the premalignant lesions (sensitivity, 16.9%;
      specificity, 97.8%; positive predictive value, 23.3%). Twelve of the premalignant
      lesions had positive smear results and a negative DVI, with none of them being of
      a high grade. CONCLUSIONS: Direct visual inspection is feasible and had superior
      sensitivity compare with cervical cytologic analysis in detecting premalignant
      lesions of the cervix. Direct visual inspection can be used as a primary
      screening tool with a satisfactory low biopsy rate in low-resource settings or
      where cytologic services are suboptimal.

PMID- 15874832
TI  - Fungal species changes in the female genital tract.
AB  - BACKGROUND: Candidal vaginitis has traditionally been associated with Candida
      albicans. OBJECTIVE: Two changes occurred over the past decade: first, the
      dispensing of over-the-counter (OTC) topical antifungals, and second, the
      approval of oral fluconazole 5 years later. Both have excellent activity versus
      C. albicans, but less activity versus nonalbicans species. MATERIALS AND METHODS:
      To determine if there has been a shift in species causing vaginitis, swabs were
      obtained from 156 symptomatic patients during the period after the release of OTC
      antifungals, but before fluconazole's approval. Specimens were inoculated onto
      nonselective mycotic agar, with growth transferred to selective media. RESULTS:
      One hundred eleven patients had a diagnosis of vulvovaginal candidiasis confirmed
      with yeast isolated. Ninety (81.1%) were identified as C. albicans. Of the 21
      nonalbicans species, 15 (71.4%) were Candida glabrata. CONCLUSIONS: Therefore, it
      appears that after decades of the predominance of Candida albicans, a change may
      be occurring resulting in an increase in nonalbicans species.

PMID- 15874833
TI  - Measurement of colposcopy-associated distress using the psychosocial effects of
      having an abnormal pap smear-questionnaire in a Latina population.
AB  - OBJECTIVE: To elicit factors associated with distress in Latina colposcopy
      patients. MATERIALS AND METHODS: Three hundred two Caribbean Latinas attending a
      colposcopy clinic took the Psychosocial Effects of Having an Abnormal Pap Smear
      Questionnaire, which measures distress using 14 questions grouped into four
      dimensions. A Spanish-language translation was tested. RESULTS: Age ranged from
      15 to 65 years (mean = 27 years); 220 of 301 women (73%) were undergoing a first
      colposcopy; 51 of 301 (16.9%) reported depression, and 25 of 298 (8.4%) reported
      anxiety. A majority of women were distressed at the prospect of having cancer
      (166/299; 55.6%), of their results being positive for cancer (164/299; 54.8%),
      and of dying (150/300; 50%); "worry about the ability to have a baby" and
      "feeling tense" during the procedure followed. Younger women (<27 years) scored
      higher (p < 0.03) on all four dimensions. First-time patients scored higher on
      all questions and dimensions; "worry about infectivity" and "effect on sexual
      relationships,"p = .05 and p = .005. A Spanish translation correlated well with
      English, Po = (0.83-1.0), kappa >/= 0.73, for 13 of 14 questions. Depressed or
      anxious patients and Spanish speakers were not more distressed than their
      counterparts. CONCLUSIONS: The prospect of having cancer and dying is the
      greatest source of distress in Caribbean Latina colposcopy patients, not the
      procedure itself. Younger and first-time patients were more distressed than
      older, experienced ones. Speaking Spanish was not associated with greater
      distress.

PMID- 15874834
TI  - Optimal cutoff of the hybrid capture II human papillomavirus test for self
      collected vaginal, vulvar, and urine specimens in a colposcopy referral
      population.
AB  - OBJECTIVE: To estimate the optimal relative light unit ratio, as a measure of
      viral load, of the Hybrid Capture II human papillomavirus (HPV) test in self
      collected specimens for detecting cervical intraepithelial neoplasia (CIN).
      METHODS: Two hundred women referred for colposcopy with abnormal cytologic, self
      collected vaginal and vulvar swabs and urine for HPV testing. The receiver
      operating characteristic (ROC) curve method was used to estimate optimal cutoffs
      for the Hybrid Capture II test. The reference standard was colposcopy, with
      directed biopsy as required. RESULTS: The estimated optimal cutoffs of the
      relative light unit ratio for detecting CIN 2 or higher for urine, vulvar, and
      vaginal samples gave sensitivities of 72.4%, 82.8%, and 89.0% and specificities
      of 57.0%, 52.1%, and 55.9%, respectively. At the manufacturer's recommended 1.0
      cutoff, sensitivities were 44.8%, 62.1%, and 86.2% for urine, vulvar, and vaginal
      samples, with specificities of 69.7%, 62.7%, and 53.5%, respectively. The
      likelihood ratios (likelihood of being truly positive after a positive test
      result) were similar for the optimal and the 1.0 cutoff. CONCLUSIONS: The ROC
      curve methods did not improve the overall diagnostic accuracy of the Hybrid
      Capture II test compared with the 1.0 relative light unit ratio cutoff.

PMID- 15874835
TI  - Primary adenocarcinoma of the vagina with mucinous-enteric differentiation: a
      report of two cases with associated vaginal adenosis without history of
      diethylstilbestrol exposure.
AB  - Primary adenocarcinoma of the vagina is rare, and mucinous-enteric
      differentiation is exceptional. A few sporadic cases of primary vaginal
      adenocarcinoma with mucinous-enteric differentiation have been reported. Reports
      of the clinical histories, pathologic findings, and immunohistochemical studies
      of two cases of primary vaginal adenocarcinomas in a 67-year-old and in a 45-year
      old woman are presented. Knowledge of the differentiation of Mullerian epithelium
      and immunohistochemistry studies are helpful to better characterize these tumors.

PMID- 15874836
TI  - Improving cytologic samples from the uterine cervix: a simple visual instruction.
AB  - OBJECTIVE: To improve the quality of smears from uterine cervix. MATERIALS AND
      METHODS: Fifteen photographs of different types of cervixes (nulliparous,
      multiparous, ectopia, and others) were shown to a group of physicians and
      technicians who send samples to our laboratory. We had previously evaluated
      accuracy of sampling the transformation zone and compared results of the test
      group with our previous evaluation using Student's t test. RESULTS: The rate of
      transformation zone sampling increased from 45% to 77% (p = 0.0001) after
      physicians and technicians saw the photographs and received instructions.
      CONCLUSIONS: This method is simple and very effective for the improving sampling
      of the uterine cervix by clinicians and other health providers.

PMID- 15874837
TI  - Pain at the vulvar vestibule: a web-based survey.
AB  - OBJECTIVE: To assess the prevalence, characteristics, and ethnic distribution of
      pain in the vulvar vestibule among a national sample of women completing a web
      based survey. METHODS: Female participants of the SurveySpot Internet research
      panel (Survey Sampling International) were invited via e-mail to respond to a web
      based questionnaire on women's health issues. The frequency and characteristics
      of reported pain of the vulvar vestibule were assessed among 994 respondents,
      using univariate and multivariate analyses. RESULTS: Between May 24, 2002, and
      June 6, 2002, 730 non-African American women and 364 African American women
      responded to the invitation to participate, and 94.5% completed the survey. A
      history of pain at the vulvar vestibule was reported by 288 women (27.9%), with
      80 (7.8% of the initial 1032) reporting pain within the past 6 months, 31 (3.0%)
      reporting pain that lasted 3 or more months, and 18 (1.7%) reporting vestibular
      pain lasting 3 or more months that occurred within the past 6 months. The
      prevalence of pain was similar in African American and non-African American
      women. CONCLUSIONS: The prevalence of pain at the vulvar vestibule is more common
      than previously estimated. The perception that vulvar pain is rare among African
      American women was not supported in this survey.

PMID- 15874838
TI  - Vulvar melanoma: review of diagnosis, staging, and therapy.
AB  - OBJECTIVES: To update, assimilate, and bridge the contemporary literature on
      vulvar and cutaneous melanoma regarding diagnosis, staging, and therapy to
      provide a useful clinical reference for managing and counseling for affected
      patients. MATERIALS AND METHODS: A computerized search for reports in the
      literature up to June 2003 was carried out using PubMed and MEDLINE databases.
      Multidisciplinary involvement was used in evaluating the available data and
      formulating conclusions. RESULTS: More than 300 reports were reviewed. Diagnosis,
      staging, and therapy aspects of vulvar melanoma are summarized. CONCLUSIONS:
      Vulvar melanoma represents a subtype of cutaneous melanoma, with similar
      prognostic and staging factors. The most recent American Joint Committee on
      Cancer staging system for cutaneous melanoma is applicable to vulvar melanoma.
      Sentinel lymph node biopsy is reliable for staging the regional lymph node basin
      for vulvar melanoma. Standardized documentation of clinical and histopathologic
      parameters is needed to standardize grouping of cases for future comparison
      studies.

PMID- 15874840
TI  - The vaginal vestibule.
AB  - OBJECTIVES: Vulvar vestibule is a common term in the medical nomenclature. In our
      view, this term is inaccurate. MATERIALS AND METHODS: Herein, we provide evidence
      from embryologic, anatomic, and architectonic textbooks that shows the links
      between the vestibule and vagina. RESULTS: Our research proves that the term
      vulvar vestibule does injustice to the area it describes. CONCLUSIONS: The
      correct term for vulvar vestibule actually is vaginal vestibule.

PMID- 15874842
TI  - Clinical question: ask the experts.

PMID- 15874841
TI  - Hom study course: winter 2004.
AB  - OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or
      practitioner who is seeking to develop or enhance his or her colposcopic skills.
      The goal of the course is to present colposcopic cases that are unusual or
      instructive in terms of appearance, presentation, or management or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ACCME ACCREDITATION: The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to sponsor
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 credit hour Category I of the Physician's
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply. The Home Study Course is planned and produced in
      accordance with the ACCME's Essential Areas and Elements.

PMID- 15874843
TI  - New cervical cancer screening guidelines: do they signal the end of the annual
      pap test?

PMID- 15874844
TI  - Managing women found to have invasive cervical cancer at the time of simple
      hysterectomy for benign indications.

PMID- 15874845
TI  - Telemedicine network telecolposcopy compared with computer-based telecolposcopy.
AB  - OBJECTIVES: To compare computer-based telecolposcopy with telemedicine network
      telecolposcopy. MATERIALS AND METHODS: An on-site expert and local clinician at
      two rural sites conducted colposcopic examinations on 264 women. Colposcopic
      images were captured and transmitted to two other experts at a remote location
      using a statewide telemedicine system and a computer and modem-based system.
      Sensitivity and specificity, agreement of examination adequacy and management,
      effects of delayed interpretations, and costs were compared for each system.
      RESULTS: A greater rate of satisfactory colposcopy results was reported by the
      telemedicine network (66.1%) compared with computer-based (43.6%) telecolposcopy
      (p < .0001). Greater rates of cervical biopsy (p = .005) and endocervical
      curettage (p = .03) were required by delayed telecolposcopy compared with
      immediate telecolposcopic services. There were no significant differences in
      sensitivity of detecting cervical neoplasia among the types of the
      telecolposcopy. Computer-based telecolposcopy cost 28 dollars less per patient
      than telemedicine network telecolposcopy. CONCLUSIONS: Computer-based
      telecolposcopy may be a reasonable, cost-effective adjunct to on-site colposcopy
      for evaluating women in medically underserved areas. Synchronous telecolposcopic
      examination minimizes histologic sampling and improves consultation.

PMID- 15874846
TI  - Radical parametrectomy for occult cervical carcinoma detected posthysterectomy.
AB  - OBJECTIVE: There are no randomized studies of the two therapeutic alternatives
      (surgery or radiotherapy) for occult cervical carcinoma, and survival rates in
      the absence of residual cancer seem to be similar for both. This article presents
      our experience with radical reoperation for occult cervical carcinoma. MATERIALS
      AND METHODS: Eleven patients with occult cervical cancer, primary invasive tumor
      >/=0.5 cm and </=3.0 cm, free margins in the hysterectomy specimen, and absence
      of clinically evident residual tumor were reoperated (radical parametrectomy with
      partial colpectomy and pelvic lymphadenectomy). RESULTS: Histopathologic
      examination after reoperation showed no evidence of residual disease in nine
      cases and metastasis in lymph nodes in two cases, one of them with parametrial
      involvement. Survival was 100% among disease-free cases on reoperation and 0% in
      cases with residual disease (5-year follow-up). CONCLUSIONS: Radical reoperation
      allows disease staging, sorting of patients into risk groups, and avoidance of
      radiation therapy in more than two thirds of the cases of occult cervical
      carcinoma.

PMID- 15874847
TI  - Using the cone biopsy to compare colposcopy clinics in new york and london.
AB  - OBJECTIVE: To assess whether there were significant differences in cytologic and
      colposcopic assessments associated with conization specimens at a colposcopy
      clinic in New York compared with a colposcopy clinic in London. MATERIALS AND
      METHODS: A retrospective histopathologic survey of patients evaluated at the Mt.
      Sinai Hospital Colposcopy Clinic (MSH) in New York City and the Royal Free
      Hospital Colposcopy Clinic (RFH) in London between January 1, 1997, and December
      31, 1998, was reviewed. Study groups included all patients who underwent
      conization at either clinic. Referral cytologic results, colposcopic findings,
      and conization histologic results were compared. RESULTS: Two hundred three cases
      from MSH and 457 cases from RFH were reviewed. Most patients undergoing
      conization in either clinic were referred with Pap smears suggesting high-grade
      squamous intraepithelial lesions (MSH, 77%; RFH, 77%). Colposcopic biopsy was
      performed on all patients at MSH. At RFH, colposcopic-directed punch biopsy was
      not performed on 35% of the patients who would have been treated regardless of
      biopsy results. There is a significant difference in the distribution of cone
      histologic diagnosis between the two clinics (p = .02); there are proportionally
      more women diagnosed with high-grade disease in RFH than in MSH, where there are
      more normal and low-grade cone histologic results. According to the kappa
      coefficients, there is only slight agreement between the Pap smear cytologic
      results and punch biopsy with the conization histologic results for either clinic
      (MSH, kappa = 0.13; RFH, kappa = 0.19), with the RFH performing slightly better.
      CONCLUSIONS: This study shows exact agreement between cytologic and final
      conization diagnosis and colposcopic biopsy and final conization as 47% to 64%.
      Treatment decisions and outcomes are different between the two clinics, with the
      RFH clinic performing fewer biopsies and having more procedures yielding high
      grade disease. Recommendations regarding changing colposcopic practices could
      best be made after a prospective study.

PMID- 15874848
TI  - Abnormal pap smears in teenage mothers and the association with domestic
      violence, homelessness, and Chlamydia.
AB  - OBJECTIVE: To assess the incidence of Pap smear abnormalities and cervical
      intraepithelial neoplasia (CIN) on cervical biopsy results in teenage mothers and
      to establish if there are associations with social disruption. PATIENTS AND
      METHODS: A prospective study of 498 pregnant teenagers was performed at three
      Australian hospitals. Enrolled patients had a Pap smear performed. Women with
      abnormal Pap smear results underwent colposcopy with directed biopsy of the
      cervix. Independently, women were interviewed to identify demographic and social
      variables. Variables associated with an abnormal Pap smear result were analyzed
      using a mixed model of analysis. RESULTS: Four hundred fifty-seven patients
      participated in the study (response rate, 92%). The prevalences of low- and high
      grade squamous intraepithelial lesions on Pap smear were 37 in 1,000 and 13 in
      1,000, respectively. The prevalence of CIN 1 was 35 in 1,000 and of CIN 2,3 was
      15 in 1,000. In univariate analysis, teenagers with abnormal Pap smear results
      were significantly more likely to have a history of exposure to domestic violence
      (odds ration [OR], 7.10; 95% CI, 2.76-18.53), be homeless (OR, 6.82; 95% CI, 2.59
      17.83), to have coexisting Chlamydia infection (OR, 5.44; 95% CI, 1.59-17.64), or
      be current users of illegal drugs or have a history of illegal drug use (current:
      OR, 3.06; 95% CI, 1.22-7.69; history: OR, 2.75; 95% CI, 1.04-7.53). Exposure to
      domestic violence, homelessness, and Chlamydia infection remained significant on
      multivariate analysis (p < .05). CONCLUSIONS: The incidence of CIN in pregnant
      teenagers is high and is associated with domestic violence, homelessness, and
      Chlamydia infection.

PMID- 15874849
TI  - The Pap test at follow-up colposcopy examinations: usefulness in the enhanced
      detection of cervical neoplasia.
AB  - OBJECTIVE: The frequency at which results of the Pap test performed at follow-up
      colposcopy examinations were more abnormal than the concurrent tissue specimens
      and the frequency at which the Pap result gain in high-grade squamous
      intraepithelial lesion (HSIL) resulted in the increased detection of cervical
      intraepithelial neoplasia 2,3 were investigated. MATERIALS AND METHODS: Pap test
      and concurrent tissue samples obtained at all follow-up colposcopy examinations
      in the year 2000 were coded for comparability of results and were ranked in
      ascending order from normal to malignant. The frequency at which the Pap test
      results were more abnormal than the concurrent tissue results was calculated.
      Results of subsequent cervical investigations were retrieved for all with a Pap
      test gain in diagnosis of HSIL. RESULTS: In 35% of 2,902 examinations (n =
      1,027), the Pap test results were more abnormal than the tissue specimens. The
      gain in diagnosis was HSIL in 2% (63 of 2,902) and low-grade squamous
      intraepithelial lesion or better in 33% (964 of 2,902). Among those with a gain
      in HSIL, cervical intraepithelial neoplasia 2,3 or cancer was tissue-confirmed in
      28 samples, for a health benefit of the Pap test of 1.0% (28 of 2,902).
      CONCLUSIONS: The usefulness of the Pap test performed at follow-up colposcopy
      examinations for the enhanced detection of CIN 2,3 in this cohort is minimal, and
      the practice safely could be discontinued.

PMID- 15874850
TI  - Long-term surveillance is required for all women treated for cervical
      adenocarcinoma in situ.
AB  - OBJECTIVE: To measure the recurrence rate of disease in women treated for
      cervical adenocarcinoma in situ (ACIS) by either hysterectomy or conservative
      surgical management. PATIENTS AND METHODS: One hundred patients with a
      histopathologic diagnosis of ACIS or glandular dysplasia were identified in a
      retrospective clinicopathological review. Sixty-seven of the 100 patients were
      managed conservatively by local excision and were followed up for a mean period
      of 59 months (range, 1-222 months). The remaining 33 patients underwent
      hysterectomy as the primary management method and were followed up for a mean of
      88 months (range, 1-248 months). If there was histologic documentation of ACIS or
      invasive adenocarcinoma more than 1 year after treatment, this was considered a
      recurrence. RESULTS: A total of four recurrences were noted in the 100 patients,
      three in the conservatively managed group and one in the hysterectomy group. Two
      late recurrences were noted at 97 and 153 months, one each in the conservatively
      managed and hysterectomy groups. CONCLUSIONS: Women who have been treated for
      cervical ACIS require long-term surveillance for at least 10 years regardless of
      whether they have undergone hysterectomy or conservative management.

PMID- 15874851
TI  - Performance of direct visual inspection of the cervix with acetic acid and
      magnification in a previously screened population.
AB  - OBJECTIVE: To assess the screening performance of direct visual inspection with
      acetic acid and x2 magnification (VIAM) in a previously screened population, as
      performed by experienced gynecologic nurses with minimal training in VIAM.
      PATIENTS AND METHODS: Performance of VIAM was evaluated in 2,080 women from a
      population-based cohort in Guanacaste, Costa Rica, 5 years after they had
      negative enrollment results of conventional and liquid-based cytologic analysis,
      cervigram, and human papillomavirus DNA by Hybrid Capture Tube Test (Digene
      Corporation, Gaithersburg, MD). The VIAM results were compared with repeat
      conventional Pap smears, liquid-based cytologic examinations, and cervicography,
      with adjudication of differences by reference to MY09/MY11 L1 consensus primer
      polymerase chain reaction detection of oncogenic human papillomavirus DNA.
      RESULTS: Less than 5% of women were classified as having positive results using
      VIAM. The VIAM positivity was also very low among women with high-grade squamous
      intraepithelial lesion conventional Pap smear results (8.3%), high-grade squamous
      intraepithelial lesion liquid-based cytologic results (6.3%), or cervigrams
      suggesting cervical intraepithelial neoplasia 2,3 or cancer (30%). The VIAM
      positivity was not associated with human papillomavirus DNA positivity.
      CONCLUSIONS: As we practiced it, VIAM was not sensitive for detection of possibly
      serious incident cervical lesions in this previously screened population where
      cytologic screening is in place.

PMID- 15874852
TI  - Evidence supporting the current management guidelines for high-grade squamous
      intraepithelial lesion cytology.
AB  - OBJECTIVE: The study was undertaken to provide consensus guidelines for the
      management of women with a cytologic interpretation of high-grade squamous
      intraepithelial lesion (HSIL) on cytologic examination. This review article
      presents relevant literature supporting the proposed guidelines. PARTICIPANTS: An
      independent panel of 121 experts in various aspects of the diagnosis and
      management of cervical cancer precursors, including representatives from 29
      participating professional organizations, federal agencies, national and
      international health organizations, and others were invited by the American
      Society for Colposcopy and Cervical Pathology. CONSENSUS PROCESS: Guidelines for
      the management of women with HSIL cytologic results were developed through a
      multistep process. Draft management guidelines were developed by the HSIL working
      group after formal literature reviews and obtained input from the professional
      community at large by way of an interactive internet-based bulletin board. At the
      American Society for Colposcopy and Cervical Pathology Consensus Conference,
      September 6 through 8, 2001, in Bethesda, Maryland, the guidelines were
      discussed, revised, and adopted by formal vote. CONCLUSIONS: Evidence-based
      guidelines have been developed for the management of women with HSIL cytologic
      results.

PMID- 15874853
TI  - Langerhans cell histiocytosis of the vulva: two case reports.
AB  - This report describes the histopathologic results of Langerhans cell
      histiocytosis of the vulva and options for treatment. We present two new cases
      demonstrating vulvar manifestations of disease and their course of treatment with
      a review of the literature. Langerhans cell histiocytosis of the female genital
      tract is rare. The disease cannot be diagnosed without biopsy of cutaneous
      lesions. Langerhans cell histiocytosis of the vulva is a rare disorder with few
      options for treatment.

PMID- 15874854
TI  - Evidence-based screening and management guidelines address the realistic concerns
      of practicing clinicians and pathologists.

PMID- 15874855
TI  - Clinical question: ask the experts. Management of cervical intraepithelial
      neoplasia 2 in adolescent.

PMID- 15874856
TI  - Home study course: spring 2004.
AB  - OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or
      practitioner who is seeking to develop or enhance his or her colposcopic skills.
      The goal of the course is to present colposcopic cases that are unusual or
      instructive in terms of appearance, presentation, or management or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ACCME ACCREDITATION: The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to sponsor
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 credit hour Category I of the Physician's
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply. The Home Study Course is planned and produced in
      accordance with the ACCME's Essential Areas and Elements.

PMID- 15874858
TI  - Happy Birthday, ASCCP.

PMID- 15874859
TI  - Lower genital tract disease.

PMID- 15874860
TI  - ASCCP 2004 Distinguished Scientific Achievement Award given to Raymond H.
      Kaufman, MD.

PMID- 15874861
TI  - Pitfalls in the diagnosis of cervical intraepithelial neoplasia 1.
AB  - OBJECTIVE: This review article outlines the issues involved in (1) the cytologic
      diagnosis of low-grade squamous intra-epithelial lesion (cervical intraepithelial
      neoplasia [CIN] 1), (2) histologic diagnosis of CIN 1, (3) the advantages and
      disadvantages of various management strategies for CIN 1 confirmed by biopsy, and
      (4) the evolving technology that may be useful for predicting the course of the
      disease. MATERIALS AND METHODS: A MEDLINE search was conducted using the search
      terms cervical intraepithelial neoplasia, low-grade dysplasia, mild dysplasia,
      low-risk squamous intraepithelial lesion, mild dyskaryosis, HPV, colposcopy,
      histology, and cytology. RESULTS.: Using a loop electrosurgical excision
      procedure or cone biopsy assessment of the cervix as the gold standard, a
      cytologic assessment of CIN 1 alone results in a high false-positive rate (51.5%)
      and a false-negative rate (24%) for CIN 3. The appropriate second test after low
      grade squamous intraepithelial lesion (CIN 1) cytologic results includes repeat
      cervical cytologic analysis. Subsequent human papillomavirus testing provides no
      advantage and increases the cost of care. Immediate referral to colposcopy is
      costly but minimizes the percent of women lost to follow-up. Using a loop
      electrosurgical excision procedure or cone biopsy assessment of the cervix as the
      gold standard, the colposcopically directed biopsy may give a false-positive
      result (11.7%) or false-negative result (up to 31%) for CIN 3. One contributing
      issue is the moderate interobserver reliability of histologic analysis (kappa=
      0.46). There are advantages and disadvantages to both the immediate and expectant
      management strategies. The most crucial concern for immediate treatment is
      overtreatment, and that for expectant management the high rate of patients lost
      to follow-up. Novel technologies, including MIB-1, p16(INK)4a, and genetic
      assessments, may be helpful in predicting those CIN 1 lesions destined to
      progress or to persist. CONCLUSIONS: The cytologic and histologic diagnosis of
      CIN 1 is fraught with problems related to the subjectivity of the diagnosis. Both
      management options are also fraught with concerns. Any technique that can better
      predict disease course would be an advantage to the care of women with this
      abnormality.

PMID- 15874862
TI  - Human papillomavirus vaccine acceptability among parents of 10- to 15-year-old
      adolescents.
AB  - OBJECTIVE: To determine human papillomavirus (HPV) vaccine acceptance among
      parents of 10- to 15-year-old adolescents. MATERIALS AND METHODS: Five hundred
      seventy-five parents or guardians completed a 30-question survey regarding their
      knowledge of HPV and acceptance of an HPV vaccine. Afterward, subjects read an
      HPV educational fact sheet and completed a 26-question survey. Results were
      compared using the chi test, analysis of variance, and McNemar's test. RESULTS:
      More than 60% of subjects had a general understanding of HPV. Parents opposed to
      the HPV vaccine were more likely to believe it would promote earlier initiation
      of coitus compared with parents supportive or undecided about vaccination (24%,
      9%, and 6%, respectively; p = .003). Of the subjects initially opposed to or
      undecided about the HPV vaccine, 37% and 65%, respectively, supported HPV
      vaccination after an educational intervention. CONCLUSIONS: A brief educational
      intervention significantly improved parent's acceptance of the HPV vaccine. The
      negative impact of an HPV vaccine perceived as condoning early initiation of
      sexual intercourse seems to be minimal.

PMID- 15874863
TI  - The bartholin gland cyst: past, present, and future.
AB  - Bartholin gland cysts account for 2% of all gynecologic visits per year. The
      treatment of Bartholin gland cysts has evolved from a complicated, bloody
      procedure requiring general anesthesia to, most recently, a simple puncture of
      the cyst and placement of a drain performed in the office. Although treatments
      for Bartholin gland cysts seem simple on the surface, recurrent cysts as well as
      diagnosing simple cysts versus abscesses versus malignant tumors can complicate
      treatment for this common problem. This article exams a history of the treatment
      of Bartholin gland cysts, including the use of the traditional treatments of
      excision, fistulization, marsupialization, as well as cauterization with carbon
      dioxide laser and silver nitrate. Modern variations are discussed, including the
      use of hydrodissection for excision, as well as the application of magnetic
      resonance imaging use in devising treatment for recurrent cysts.

PMID- 15874864
TI  - Vesicovaginal fistula resulting from loop electrosurgical excision in a woman
      with intraepithelial neoplasia of the cervix and vagina: a case report.
AB  - A 52-year-old woman had concomitant cervical intraepithelial neoplasia (CIN)
      grade 3 and vaginal intraepithelial neoplasia grade 3. On performing a loop
      electrosurgical excision procedure, a vesicovaginal fistula accidentally
      occurred. The vaginal intraepithelial neoplasia covering the anterior fornix
      could have been a contributing factor in the occurrence of the fistula.

PMID- 15874865
TI  - Using patient history to predict high-grade cervical dysplasia and cancer in
      women with borderline cervical cytologic results.
AB  - OBJECTIVE: To determine whether demographic and lifestyle factors can be used to
      triage women with borderline cervical cytologic results. MATERIALS AND METHODS:
      Demographic and medical information were collected from women undergoing
      colposcopy for a cytologic result read as atypical squamous cells of undetermined
      significance (ASCUS) or low-grade squamous intraepithelial lesion in the
      gynecology clinic of an urban public hospital between July 1, 1996, and December
      1, 1999. Colposcopy and subsequent histologic results were reviewed. Multivariate
      analysis was used to define predictors of high-grade cervical disease. RESULTS:
      From among 1725 eligible women, 283 women (16%) with ASCUS or low-grade squamous
      intraepithelial lesion results were found to have high-grade cervical disease
      (113 women with ASCUS results [13%] and 170 women with low-grade squamous
      intraepithelial lesion results [21%]). In multivariate analysis, pregnant women
      were less likely to have high-grade disease (odds ratio, 0.36; 95% CI, 0.17
      0.79). Women with three or more lifetime sexual partners were more likely to have
      high-grade disease (odds ratio, 1.75; 95% CI, 1.31-2.34). However, a triage
      scheme tracking pregnant women with fewer than three lifetime partners to
      observation without colposcopy would have excluded only 51 of the 1725 women
      eligible (3%). Other combinations of risk factors had inadequate sensitivity or
      specificity for high-grade disease. Separate models for ASCUS showed that only
      having fewer than three lifetime sexual partners was associated with lower risk
      of high-grade histologic results (odds ratio, 0.56; 95% CI, 0.36-0.89), but
      excluding women with fewer partners would have missed 27 of 110 cases (25%) of
      high-grade disease. CONCLUSIONS: History and demographic information are
      inadequately sensitive for use in triage of women with borderline cytologic
      findings. Colposcopy or triage using human papillomavirus DNA tests remain
      indicated.

PMID- 15874866
TI  - Interobserver variability of colposcopic interpretations and consistency with
      final histologic results.
AB  - OBJECTIVE: To evaluate the interobserver reliability of colposcopy and the
      prediction of final histologic results. MATERIALS AND METHODS: Visibility of the
      squamocolumnar junction, presence and grading of atypical transformation zone
      (ATZ), and presence and grading of cervical intraepithelial neoplasia (CIN) were
      assessed by nine expert colposcopists in 100 cervigrams. Pairwise kappa, group
      kappa, and class-specific kappa values were computed. Frequency and degree of
      interobserver disagreement on CIN and ATZ grading and correlation with histologic
      results were studied. RESULTS: The median pairwise kappa and the group kappa
      values were excellent for ATZ detection, acceptable for the squamocolumnar
      junction, and poor for the other variables; the presence of ATZ had a sensitivity
      for CIN of 90.2% and a specificity of 48.6%; the colposcopic impression of high
      grade CIN had a sensitivity of 54.4% and a specificity of 88%. CONCLUSIONS: Some
      colposcopic predictions are reproducible between observers, predictive of the
      histologic results, and can be integrated in the algorithm for the management of
      patients with abnormal Pap smear results.

PMID- 15874867
TI  - Human papillomavirus and abnormal Pap test results in Vietnamese-American women:
      a pilot case-control study.
AB  - OBJECTIVE: To evaluate the relationship between abnormal Pap test results and
      human papillomavirus (HPV) in Vietnamese-American women, who have the highest
      cervical cancer incidence in the United States. MATERIALS AND METHODS: In 2001,
      we obtained specimens from 117 Vietnamese women, 24 with abnormal Pap test
      results including atypical squamous cells of undetermined significance (cases)
      and 93 with normal Pap test results (controls), as classified by the 1991
      Bethesda System. We used L1 consensus primers MY09/MY11 to perform HPV polymerase
      chain reaction analysis and type-specific probes to perform genotyping. RESULTS:
      Thirteen cases (54%) and 6 controls (6%) were HPV positive (p < .001). Ten of 24
      cases (42%) and 0 controls (0%) had high-risk HPV types (16, 18, 45, 53, 56, or
      66; p < .001). High-risk HPV types were significantly associated with increasing
      severity of Pap test results. CONCLUSIONS: Compared with those with normal Pap
      test results, Vietnamese-American women with abnormal Pap test results were more
      likely to have high-risk HPV types. Higher cervical cancer incidence among these
      women is likely the result of less frequent Pap screening rates and not different
      biology.

PMID- 15874868
TI  - Beyond human papillomavirus: the cervix, exogenous secondary factors, and the
      development of cervical precancer and cancer.
AB  - Human papillomavirus (HPV) is the necessary but probably not sufficient cause of
      cervical precancer and cancer. Secondary exogenous and endogenous factors, HPV
      cofactors, may contribute to the probability of a cancer-associated (oncogenic)
      HPV infection progressing to cervical precancer and cancer. For these cofactors
      to influence the natural history of HPV infection, they must act on cervical
      tissue to promote viral persistence, progression to precancer or cancer given
      viral persistence, or both. The aim of this review was to examine briefly the
      impact these factors may have on carcinogenesis of the cervix. Specifically, the
      roles of the cervical transformation zone, cervical immunity, inflammation and
      coinfection, and exposure to the main HPV cofactors (smoking, oral contraceptive
      use, and multiparity) are discussed.

PMID- 15874869
TI  - Clinical question: ask the experts.

PMID- 15874870
TI  - Home study course: Summer 2004.
AB  - OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or
      practitioner who is seeking to develop or enhance his or her colposcopic skills.
      The goal of the course is to present colposcopic cases that are unusual or
      instructive in terms of appearance, presentation, or management, or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ACCME ACCREDITATION: The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to provide
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 hour Category I credit of the Physician's
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply. The Home Study Course is planned and produced in
      accordance with the ACCME's Essential Areas and Elements.

PMID- 15874871
TI  - Anal dysplasia in HIV-infected women with cervical and vulvar dysplasia.
AB  - OBJECTIVE: To describe the findings of high-resolution anoscopy (HRA) in human
      immunodeficiency virus (HIV)-infected women with a history of lower genital tract
      dysplasia. MATERIALS AND METHODS: A retrospective chart review of all HIV
      infected women undergoing HRA from 2002 to 2003 was conducted. Demographic and
      clinical information, including the most recent cervical and vaginal cytologic
      results and colposcopic evaluations, were collected from medical records. These
      data were compared with anal cytologic and histologic findings from HRA. RESULTS:
      Eight patients were identified, with a mean age of 42 years. The mean duration of
      known HIV infection was 12 years. All eight patients had a previous history of
      treatment for cervical dysplasia or carcinoma. Five patients also had a history
      of high-grade vulvar dysplasia. The most recent cervical and vaginal cytologic
      results for all patients were abnormal. Seven patients underwent HRA because of
      suspected anal intraepithelial neoplasia (AIN); of these, four patients had
      perianal warts and three had diffuse high-grade vulvar dysplasia. One patient was
      referred for HRA because of high-grade dysplasia on vaginal cytologic analysis
      with a negative colposcopic and urologic evaluation. All eight patients (100%)
      had abnormal anal cytologic results with histologically proven AIN. Five patients
      had AIN 2,3, and three patients had AIN 1 and anal condyloma. Two of the three
      patients with AIN 1 had high-grade perianal dysplasia. CONCLUSIONS: High
      resolution anoscopy identified anal dysplasia in 100% of eight HIV-infected women
      with human papilloma virus-related dysplasia of the lower genital tract. High
      resolution anoscopy should be considered as part of the evaluation for the extent
      of disease in HIV-infected women with cervical and vaginal dysplasia, condyloma,
      and dysplasia of the perineum.

PMID- 15874872
TI  - Transepithelial sampling of the uterine ectocervix with a stiff-bristled, spiral
      shaped brush.
AB  - OBJECTIVE: To measure the depth of sampling of the uterine ectocervix with the
      use of a stiff-bristled, spiral-shaped brush (SpiraBrush Cx; Trylon Corporation,
      Torrance, CA). MATERIALS AND METHODS: Eligible hysterectomy specimens were
      identified. The ectocervix was brushed with an inked SpiraBrush Cx in four
      quadrants with either light (gentle) or heavy (forceful) pressure. The depth of
      sampling was determined histologically. RESULTS: Four normal uteri were sampled a
      total of 15 times. The entire epithelium was removed to the epithelial-stromal
      junction in three specimens and in one sample only a few basal cells remained
      with light pressure. The depth of sampling ranged from 0.2 mm to 0.4 mm. Heavy
      pressure resulted in the entire removal of epithelium in six samples, with the
      depth of sampling ranging from 0.2 mm to 0.7 mm. The stroma was disrupted in one
      sample. Results were uninformative in five samples. CONCLUSIONS: Sampling of the
      uterine ectocervix with the SpiraBrush Cx seems to be transepithelial in most
      cases.

PMID- 15874873
TI  - A cost-effectiveness analysis of screening strategies for cervical
      intraepithelial neoplasia.
AB  - OBJECTIVE: To assess the costs and usefulness of colposcopy using three screening
      strategies for cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: A
      decision model compared three screening strategies for CIN: (1) patients were
      screened annually with a conventional Pap smear, (2) patients were screened
      annually with a liquid-based cytologic method and reflex human papillomavirus
      testing for atypical squamous cells of undetermined significance results, and (3)
      patients were screened biennially with a liquid-based cytologic method and reflex
      human papillomavirus testing for atypical squamous cells of undetermined
      significance results. RESULTS: Biennial liquid-based screening was the least
      expensive strategy with a cost of $9.5 million per 100,000 patients. Annual
      liquid-based screening was the most expensive strategy at $13.7 million. Annual
      conventional screening had an intermediate cost of $11.6 million. Biennial liquid
      based screening referred the fewest patients to colposcopy (11.8%), followed by
      annual conventional screening and annual liquid-based screening (15.2% and 15.6%,
      respectively). CONCLUSIONS: Each of these treatment strategies is reasonable;
      however, biennial liquid-based screening would reduce medical costs
      significantly.

PMID- 15874874
TI  - False-negative hybrid capture II results related to altered adhesion molecule
      distribution in women with atypical squamous cells pap smear results and tissue
      based human papillomavirus-positive high-grade cervical intraepithelial
      neoplasia.
AB  - OBJECTIVE: We investigated the detection of high-risk human papillomavirus DNA
      with the Hybrid Capture II test (HCII; Digene Corporation, Beltsville, MD) and
      the presence and pattern of distribution of adhesion molecules in biopsy-proven
      high-grade neoplastic lesions containing high-risk HPV-DNA from women with ASC
      cytology results. MATERIALS AND METHODS: We screened 4,600 women and performed
      colposcopy in 278 women with atypical squamous cells cytologic results. All women
      underwent HCII and tissue-based polymerase chain reaction analysis for high-risk
      HPV subtypes. Of 33 women with cervical intraepithelial neoplasia (CIN) 2 or
      worse biopsy results, 27 biopsy specimens contained sufficient tissue to perform
      immunohistochemical testing (pathologist blinded as to cytologic and HCII
      results) for adhesion molecules beta-catenin and 21 cases for E-cadherin.
      RESULTS: Five of 27 specimens with CIN 2 or worse biopsy results (18.5%) had
      negative HCII results. All five specimens showed evidence of high-risk human
      papillomavirus by polymerase chain reaction analysis. All five showed full
      thickness distribution via immunohistochemical staining for beta-catenin. There
      was sufficient tissue to examine four of five specimens for E-cadherin, and a
      full-thickness distribution also was documented. CONCLUSIONS: Previous research
      linked false-negative cytologic results in women with high-grade CIN to altered
      adhesion molecule distribution and impaired exfoliation, and a similar phenomenon
      may be responsible for false-negative HCII results in women with atypical
      squamous cells cytologic results and high-grade CIN.

PMID- 15874875
TI  - Expression of epidermal growth factor receptor in cervical tissue and serum in
      patients with cervical neoplasia.
AB  - OBJECTIVE: We hypothesized that there may be a relationship between epidermal
      growth factor receptor (EGFR) expression in cervical tissue and serum in patients
      with cervical neoplasia. MATERIALS AND METHODS: The expression of EGFR was
      measured in cervical tissues from 23 cervical intraepithelial neoplasia patients
      and 16 cervical carcinoma patients using immunohistochemical staining and the
      level of serum EGFR extracellular domain was measured in serum from 17 cervical
      intraepithelial neoplasia patients and 14 cervical carcinoma patients using
      enzyme-linked immunosorbent assay. RESULTS: The expression of EGFR was
      significantly increased as normal cervical tissue progressed to cervical intra
      epithelial neoplasia then to cervical carcinoma (p = .009). The mean level of
      serum EGFR according to the intensity of immunohistochemical staining in
      negative, weakly positive, positive, and strongly positive staining was 19.36 +/-
      3.12 fmol/mL, 20.99 +/- 3.59 fmol/mL, 29.08 +/- 16.86 fmol/mL, and 24.34 +/-
      10.35 fmol/mL, respectively (p = .450). CONCLUSIONS: We believe that the level of
      serum EGFR may have a similar role as tumor markers such as the EGFR expression
      in cervical neoplastic tissue.

PMID- 15874876
TI  - High-risk human papillomavirus and cervical intraepithelial neoplasia at time of
      atypical squamous cells of undetermined significance cytologic results in a
      population with human immunodeficiency virus.
AB  - OBJECTIVE: Little information exists regarding high-risk human papillomavirus
      (HPV) subtypes in human immunodeficiency virus (HIV) patients with atypical
      squamous cells of undetermined significance (ASCUS) cytologic results. This study
      aimed to characterize further HPV prevalence and high-grade cervical
      intraepithelial neoplasia (CIN) in this sub-population of patients. MATERIALS AND
      METHODS: This is a secondary analysis of a prospective HPV natural history study
      involving 200 HIV-sero-positive patients. We analyzed 102 patients from this
      cohort with a cervical cytologic diagnosis of ASCUS for high-risk and low-risk
      HPV prevalence, clearance of HPV infection, progression or regression of cervical
      cytologic abnormality, and prevalence of CIN 2 or worse at the time of indicated
      colposcopy. Pap smears were slide-based and HPV testing was performed using
      nested polymerase chain reaction. RESULTS: Overall prevalence of ASCUS in the HIV
      population was 20% (40 of 200 patients). Despite a high prevalence of all HPV
      subtypes (74 of 102 subtypes; 73%), high-risk subtypes were present in only 32%
      of patients (33 of 102 patients) with ASCUS cytologic results. In 5 of 42
      patients (12%) undergoing colposcopy within 6 months of ASCUS cytologic results,
      CIN 2 or worse was found. Sensitivity, specificity, positive predictive value,
      and negative predictive value of a high-risk or intermediate-risk HPV test for
      CIN 2,3 were 100%, 70%, 31%, and 100%, respectively. Progression to high-grade
      intraepithelial lesion cytologic results after ASCUS was rare (5/64 evaluable
      patients; 8%) but persistence of low-grade cytologic results (ASCUS or low-grade
      intraepithelial lesion) was common (43/64 evaluable patients; 67%). CONCLUSIONS:
      Despite a high rate of HPV infection in the HIV population with ASCUS Pap
      results, high-risk HPV subtypes represent a minority of patients and are
      significantly associated with presence of high-grade CIN at colposcopy. High-risk
      HPV testing should be investigated further in the HIV population.

PMID- 15874877
TI  - The clinical usefulness of human papillomavirus testing in the follow-up of women
      after treatment for cervical intraepithelial neoplasia.
AB  - OBJECTIVE: To compare the effectiveness of human papillomavirus (HPV) testing and
      cervical cytologic analysis in monitoring patients after treatment for cervical
      intraepithelial neoplasia. MATERIALS AND METHODS: A retrospective study comparing
      cytologic analysis and HPV testing using the follow-up protocol recommended by
      the American Society for Colposcopy and Cervical Pathology Consensus Conference.
      Sixty-one patients were seen for a total of 193 follow-up patient visits. In 120
      visits, both cytologic and HPV results were available. Specificity, sensitivity,
      positive and negative predictive values, and the rate of referral to colposcopy
      were calculated. RESULTS: In 68 visits, both HPV and cytologic results were
      negative, and in 19, both were positive. In 21 visits, cytologic results were
      positive and HPV results were negative, and in 12 visits, cytologic results were
      negative and HPV results were positive. The specificity of cytologic analysis and
      HPV testing was 68.3% and 75.8%, respectively (p = .16). The positive predictive
      value for cytologic analysis and HPV testing was 6.5% and 7.5%, respectively, and
      the negative predictive value was 100% and 98.9%, respectively. Had either test
      been used alone, cytologic analysis would have referred 40 patients to colposcopy
      and HPV testing would have referred 31 patients. Had both been used in
      combination, 52 patients would have required colposcopy with no significant
      improvement in the amount of disease detected. CONCLUSIONS: Both cytologic
      analysis and HPV testing are equally effective in monitoring patients after
      treatment for cervical intraepithelial neoplasia. The simultaneous use of
      cytologic analysis and HPV testing significantly increased colposcopy referrals
      without increasing the amount of disease detected.

PMID- 15874878
TI  - Multicenter direct to vial evaluation of a liquid-based pap test.
AB  - OBJECTIVE: To estimate the efficacy of a fluid-based, thin-layer preparation (TP)
      compared with the conventional Pap (CP) test to detect biopsy confirmed
      precancerous cervical lesions. MATERIALS AND METHODS: A total of 10,226 evaluable
      patients at 10 separate clinical sites were screened for cervical abnormalities
      using the TP (ThinPrep pap test; Cytyc Corporation, Boxborough, MA). Results were
      compared with an historical control cohort of 20,918 patients from a similar
      patient population and with a similar patient profile who had received CP
      screening. RESULTS: The TP significantly increased the detection rate of high
      grade squamous intraepithelial lesion and more severe (HSIL+) cytologic results
      as compared with the CP smear. Overall, the TP method yielded a 59.7% increase in
      the detection of HSIL+ compared with the CP smear. Overall, the TP method yielded
      a 59.7% increase in the detection of HSIL+ compared with the conventional method
      (3.9% vs. 2.4%; p < .001). There was also a significant increase in the detection
      of low-grade squamous intraepithelial lesions with TP (p < .01). The rates of
      cancer, atypical squamous cells of undetermined significance, and atypical
      glandular cells of undetermined significance were similar for the TP and CP
      groups. CONCLUSIONS: The overall cytologic detection of HSIL and low-grade
      squamous intraepithelial lesions with the TP method was significantly increased
      compared with a control group screened with the CP method. Histologic
      confirmation showed increased detection, not an increased false-positive
      cytologic interpretation.

PMID- 15874879
TI  - The Ki-67 labeling index is not a useful predictor for the follow-up of cervical
      intraepithelial neoplasia 1.
AB  - OBJECTIVE: Our aim was to determine whether the Ki-67 immunostaining pattern,
      present on diagnosis of cervical intraepithelial neoplasia (CIN), predicts the
      change from low-grade to high-grade CIN over a 2-year period after diagnosis.
      MATERIALS AND METHODS: Of 59 cervical biopsy samples from 59 patients diagnosed
      as having cervical CIN, 35 were diagnosed as CIN 1 and 24 were diagnosed as CIN 2
      or CIN 3. The Ki-67 immunostain showed immunopositive cells in the upper two
      thirds of the epithelium in all specimens. Two hundred nuclei were counted in 25
      high-power fields in each specimen, including all of the epithelial layers, to
      determine the mean number of Ki-67-positive cells. In situ hybridization was used
      to demonstrate and type human papillomavirus. The chi test, Fisher exact test,
      Student t test, one-way analysis of variance, and Tukey test were used for
      statistical analysis, with significance set at p < .05. RESULTS: The mean Ki-67
      labeling index for CIN 1, CIN 2, CIN 3, and CIN 2,3 were, respectively, 32.5%,
      43.2%, 53.2%, and 47.8%. The statistical study showed significant differences
      between CIN 1 versus CIN 2, CIN 1 versus CIN 3, and CIN 1 versus CIN 2,3. For CIN
      1, the mean Ki-67 labeling index was 32.8% when the lesion disappeared and was
      34.6% for persisting lesions. There was no statistically significant difference.
      CONCLUSIONS: Ki-67 labeling index did not predict persisting CIN 1.

PMID- 15874880
TI  - Clinical question: ask the experts. Adenocarcinoma in situ.

PMID- 15874881
TI  - Home study course: Fall 2004.
AB  - OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or
      practitioner who is seeking to develop or enhance his or her colposcopic skills.
      The goal of the course is to present colposcopic cases that are unusual or
      instructive in terms of appearance, presentation, or management or that
      demonstrate new and important knowledge in the area of colposcopy or pathology.
      Participants may benefit from reading and studying the material or from testing
      their knowledge by answering the questions. ACCME ACCREDITATION: The American
      Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the
      Accreditation Council for Continuing Medical Education (ACCME) to provide
      continuing medical education for physicians. The ASCCP designates this continuing
      medical education activity for 1 credit hour in Category I of the Physician's
      Recognition Award of the American Medical Association. Credit is available for
      those who choose to apply. The Home Study Course is planned and produced in
      accordance with the ACCME's Essential Areas and Elements. DISCLOSURE: Faculty
      must disclose any significant financial interest or relationship with proprietary
      entities that may have a direct relationship to the subject matter. For this
      course, neither author had any such relationship to report.

PMID- 15874883
TI  - Long- and short-term effects of thyroxine on sphingolipid metabolism in rat
      liver.
AB  - BACKGROUND: Thyroid hormones are well known as modulators of signal transduction.
      Early experiments showed that sustained elevation of diacylglycerol (DAG) and
      ceramide levels in liver cells of hypothyroid rats is an essential prerequisite
      for disturbances in agonist responsiveness of hepatocytes. In this paper the
      effects of thyroxine (L-T(4)) on sphingolipid mass, synthesis, and degradation
      are investigated. MATERIAL/METHODS: The experiments were performed on either
      [1(14)C]CH(3)COOH-labeled rat liver or hepatocytes and isolated liver cell plasma
      membranes. To determine sphingolipid synthesis and degradation in the liver,
      [(14)C]palmitic acid, [methyl-(14)C]-labeled sphingomyelin (SM), and
      phosphatidylcholine were used. RESULTS: The administration of L-T(4) to animals
      was accompanied by a time-dependent accumulation of newly synthesized ceramide,
      glucosyl ceramide, and SM in liver. In hyperthyroid liver, prominent ceramide
      accumulation and acidic SMase activation was found. The addition of hormone in a
      physiological dose to the incubation or perfusion medium led to a rapid
      stimulation of de novo ceramide synthesis, transient lipid accumulation in the
      liver, followed by SM synthase activation. CONCLUSIONS: Our results indicate that
      SMases, ceramide synthesis de novo, and SM synthase are under thyroid hormone
      control. The level of ceramide is markedly elevated in the hyperthyroid liver via
      the activation of acidic SMase and lipid synthesis de novo. In experiments in
      vitro, the hormone induces a short-lived accumulation of sphingolipid, probably
      due to its reduced efflux from the liver.

PMID- 15874884
TI  - Antibodies against Stachybotrys chartarum extract and its antigenic components,
      Stachyhemolysin and Stachyrase-A: a new clinical biomarker.
AB  - BACKGROUND: IgG and IgE antibodies against Stachybotrys extract have been
      reported in allergic patients and residents of water-damaged buildings. Detection
      of these antibodies in blood was partially attributed to cross-reacting proteins
      from other fungi. There is a need for a specific method to detect antibodies
      against characteristic components of S. chartarum. MATERIAL/METHODS: We measured
      IgG and IgE antibodies against Stachybotrys hemolysin and proteinase-Stachyrase-A
      by ELISA and ELISA-inhibition techniques. RESULTS: Of 50 reference sera with IgE
      greater than 500 IU ml and positive against different mold extracts used in this
      study, significant elevation in IgG or IgE antibodies against S. chartarum
      extract was present in 25 and 21 specimens. Of these specimens 20 (80%) and 10
      (40%) were positive for IgG anti-Stachybotrys hemolysin and anti-Stachyrase-A,
      while 8 out of 21 sera (38%) and 17 out of 21 (81%) specimens were positive for
      IgE anti-Stachybotrys hemolysin and anti-Stachyrase-A respectively. Inhibition
      studies using Stachybotrys hemolysin and Stachyrase-A at a concentration of 50
      microg/ml prevented binding of anti-Stachybotrys to S. chartarum extract.
      CONCLUSIONS: Detection of IgG as well as IgE antibodies against Stachybotrys
      hemolysin and Stachyrase-A and inhibition of anti-Stachybotrys binding to
      Stachybotrys antigens indicate that Stachybotrys hemolysin and Stachyrase-A are
      two major antigenic components of S. chartarum extract, which can be used in
      antibody assays. Measurement of antibodies against these characteristic
      components of S. chartarum may be considered for demonstration of exposure and
      possibly allergy to the fungus.

PMID- 15874885
TI  - Assessing the validity of cardiac surgery risk stratification systems for CABG
      patients in a single center.
AB  - BACKGROUND: Most cardiac surgery risk stratification systems were primarily
      designed using patient-related factors to predict mortality and postoperative
      morbidity. Relative mortality rates are higher at cardiac surgery centers which
      perform surgery on elderly patients. Our aim was to assess the validity of risk
      stratification systems for our regional population. MATERIAL/METHODS: The study
      involved 1021 patients. Risk stratification was carried out using the EuroSCORE,
      Ontario, and QMMI scoring systems. Analysis comparing the scoring systems
      included sensitivity, specificity, predictive values, and receiver operating
      characteristics (ROC) curves. Accuracy was assessed using the systems' ability to
      avoid Type I and Type II errors. RESULTS: Sensitivity and specificity of the QMMI
      scoring system were 33.3% and 97.2%, of EuroSCORE 20.7% and 96.7%, and of Ontario
      21.1% and 94.4%, respectively. The best positive predictive value was for QMMI
      and EuroSCORE with 75% versus Ontario's 50%. The highest negative predictive
      value was QMMI's 85.4% versus Ontario's 78.9% and EuroSCORE's 72.0%. The best
      accuracy showed QMMI scoring with 84.5% versus Ontario's 78.9% and EuroSCORE's
      72.2%. CONCLUSIONS: All the investigated risk stratification systems were
      moderately predictive. The QMMI score showed the best predictive characteristics
      (sensitivity, specificity, and accuracy) for our patient population. The QMMI
      system had high specificity and accuracy. The EuroSCORE system showed mortality
      overprediction for our population, associated with high false negative test
      results and low accuracy. The Ontario risk stratification system often commits
      Type II errors, associated with a high rate of false positive test results and
      low accuracy.

PMID- 15874886
TI  - Leptospirosis in Guilan, a northern province of Iran: assessment of the clinical
      presentation of 74 cases.
AB  - BACKGROUND: This study was carried out to define the major clinical presentation
      and laboratory findings of leptospirosis in Guilan province, an agricultural and
      fishery area in the Caspian littoral. MATERIAL/METHODS: Cases with a clinically
      compatible illness and positive serology (immunofluorescence antibody method
      (IFA)), were included. Clinical information and other lab data were collected.
      RESULTS: Seventy-four cases, with a mean age of 47.3 +/- 12.4 years and of whom
      52 (70.3%) were male, were recruited. All had had contact with stagnant water of
      a farm within the week prior to their admission. Fever and chills were the most
      frequent chief complaint in 47 (63.5%). Fever, headache, and myalgia were
      reported by 73 (98.6%), 69 (93.2%), and 57 (77%) cases, respectively. Increased
      serum creatinine was detected in 18 (27.3%). Only in 27% of patients did CPK rise
      to 3-fold or more above the Normal Upper Limit, and in 43% of patients its level
      was within the normal range. Thrombocytopenia was noticed in 87.3%, and 15.5% of
      cases had platelets less than 20,000/mm(3). Anemia was detected in 78.4%. ESR was
      more than 100 mm/hour in 28.3%. CONCLUSIONS: History of fever, headache, and
      myalgia in patients who have been in contact with the stagnant water of rice
      fields should raise the possibility of leptospirosis in Guilan province.

PMID- 15874887
TI  - Density of platelet collagen receptors glycoprotein VI and alpha2beta1 and prior
      myocardial infarction in human subjects, a pilot study.
AB  - BACKGROUND: Prior studies evaluating whether platelet collagen receptors affect
      risk of myocardial infarction (MI) have used common polymorphisms thought to
      affect receptor density, and have yielded conflicting results. Our objective in
      the current pilot study was to obtain preliminary information on the relationship
      between platelet collagen receptor density and prior MI. MATERIAL/METHODS: We
      measured glycoprotein VI (GPVI) and integrin alpha2beta1 density by flow
      cytometry using FITC-conjugated monoclonal antibodies in consecutive subjects
      from an outpatient cardiology practice. We used a case-control design to match 77
      patients with prior MI to 77 control patients. Matching was performed on the
      basis of traditional risk factors for MI. RESULTS: The mean GPVI density was 14%
      higher in those with prior MI (P = 0.098), and the alpha2beta1 density was 6%
      higher in those with prior MI (P = 0.49). A GPVI or alpha2beta1 density within
      the lowest decile was associated with a lower MI prevalence (OR = 6.3, 95% CI:
      1.3-29.2 P = 0.009). CONCLUSIONS: Our preliminary data suggests that platelet
      collagen receptor density, when measured directly, may be related to prior
      myocardial infarction. An appropriately sized clinical study using this
      methodology is warranted to further investigate whether collagen receptor density
      serves as a novel risk factor for myocardial infarction.

PMID- 15874888
TI  - Clinical symptoms of tuberous sclerosis complex in patients with an identical
      TSC2 mutation.
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal, dominantly
      inherited neurocutaneous syndrome characterized by a wide range of neurological
      abnormalities, tumors of different organs, and variable clinical symtomatology
      and severity. TSC is caused by mutations in either of two tumor suppressor genes:
      TSC1 or TSC2. The aim of this study was to analyze the clinical picture of TSC in
      patients with an identical TSC2 mutation. We tried to discover to what extent we
      may expect variability in the clinical set of symptoms in patients with identical
      mutation of TSC2 gene. MATERIAL/METHODS: Mutations were identified in 100 of 170
      cases. There were only 4 patients with the same type of TSC2 mutation: 5238-5255
      del 18bp, del 1746 HIKRLR. Their ages were 1.5, 9, 9, and 10 years. A
      standardized clinical assessment of TSC symptoms was used. RESULTS: Epilepsy,
      depigmented spots, and periventricular calcification and cortical tubers were
      diagnosed in all the 4 patients, cardiac rhabdomyoma and angiomyolipoma of the
      kidneys in 3, and mental retardation and forehead fibroma in 2. Other symptoms
      occurred rarely or were absent. There was variability in TSC symptoms in patients
      with the identical type of TSC2 mutation. The main symptoms were present in all
      or in the majority of patients. Clinical picture also differed with the age of
      patient. CONCLUSIONS: There are many influencing factors contributing to the
      diversity of the clinical picture and pathology of TSC. Obviously, a greater
      number of cases are needed for further analysis and more precise conclusions.

PMID- 15874889
TI  - Prone versus supine position in mechanically ventilated children: a pilot study.
AB  - BACKGROUND: It is known that mechanically ventilated patients in the prone
      position have improved oxygenation compared with those supine. We did a
      prospective, randomized, controlled trial to evaluate the effect of prone
      position during mechanical ventilation, on survival in critically ill children.
      MATERIAL/METHODS: Forty-two children needing mechanical ventilation for various
      illnesses were randomized to receive initial ventilation for four hours prone or
      supine by drawing lots. Initial severity of illness and blood gases in all
      children were noted. In a crossover design, after the initial four hours the
      children were turned over and ventilated in the alternate posture for an hour.
      Oxygenation parameters and mean airway pressures were noted at one hour, four
      hours, and five hours. Mortality, duration of ventilation, and the above
      parameters were compared in the two groups. RESULTS: Initial PRISM scores were
      similar in the two groups. Mortality in the prone group was less than in the
      supine group. The odds ratio of mortality was 0.20 (95% CI 0.05-0.75). Duration
      of ventilation was similar in the two groups. The oxygenation index was
      significantly lower in the prone group at one, four, and five hours after onset
      of ventilation. CONCLUSIONS: Prone position in the first few hours of ventilation
      significantly improves gas exchange and oxygenation, reduces the mean airway
      pressures required to ventilate children, and may cause significant improvement
      in survival. Our study protocol allowed ventilator settings to be changed as
      needed during ventilation.

PMID- 15874890
TI  - Antimicrobial susceptibility of aerobic microorganisms isolated from
      intraabdominal infections in pediatric patients in Poland.
AB  - BACKGROUND: Growing resistance to antibiotics among both community-acquired and
      hospital pathogens is making the treatment of most infections increasingly
      difficult. Therefore, the aim of our multi-center study was to determine the
      antimicrobial susceptibility of the most frequent aerobic microorganisms isolated
      from children with intraabdominal infections. MATERIAL/METHODS: Bacterial
      pathogens were isolated from 256 consecutive patients treated in five large
      specialized hospitals in Poland from January 2001 to February 2002. Minimal
      inhibitory concentrations (MICs) of piperacillin, piperacillin-tazobactam,
      cefotaxime, ceftazidime and cefepime were determined by Etests. The production of
      extended spectrum beta-lactamases (ESBL) was detected by a double-disk test.
      RESULTS: Piperacillin-tazobactam was the most active agent against
      Enterobacteriaceae and Pseudomonas aeruginosa, inhibiting 92% and 78% of isolates
      respectively. Susceptibility of Enterobacteriaceae to cefotaxime, ceftazidime and
      cefepime was 73%, 73% and 87% respectively, and susceptibility of P. aeruginosa
      to both ceftazidime and cefepime was 76%. Extended-spectrum beta-lactamases were
      detected in 56% Klebsiella sp. and 11.5% E. coli, but the vast majority of these
      isolates remained susceptible to piperacillin-tazobactam (MIC(90) = 12 mg/L and
      MIC(90) = 1 mg/L, respectively). CONCLUSIONS: Piperacillin/tazobactam remains a
      valuable therapeutic option in Polish pediatric patients with intraabdominal
      infections, due to its good activity against ESbetaL-producing organisms and P.
      aeruginosa.

PMID- 15874891
TI  - Transfusion-related acute lung injury: a life-threatening transfusion reaction.
AB  - BACKGROUND: We present the case of a 57-year-old woman who developed transfusion
      related acute lung injury (TRALI) following a transfusion of packed red blood
      cells (pRBCs). CASE REPORT: A 56-year-old woman had undergone a low anterior
      resection in 2002 because of a Duke's stage D adenocarcinoma of the rectum. In
      June 2003 she was referred to our department, presenting symptoms and signs of
      ileus. Abdominal radiograph revealed multiple air-fluid levels, while a computed
      tomography scan showed disease dissemination. Colonoscopic control verified
      recurrent disease in the anastomotic area. At surgery, a palliative loop ostomy
      was generated. In the 4(th) postoperative day it was decided that one unit of
      pRBCs be transfused. pRBC administration complicated with a severe reaction,
      developing within 35 minutes of the transfusion episode. The diagnosis of TRALI
      syndrome was based on clinical signs and symptoms. Hemodynamic stabilization and
      resuscitation required low doses of epinephrine, diuretics, and a high
      concentration of inspired oxygen in combination with bronchodilators. Ventilatory
      assistance was not required. Clinical improvement occurred 12 hours later. Full
      recovery of the syndrome was observed in 6 days, while chest X-ray returned to
      normal findings within 4 days. CONCLUSIONS: TRALI syndrome is an immune-mediated
      transfusion reaction which can cause severe complications or even death. Early
      diagnosis and treatment improves survival and usually results in full recovery.
      TRALI remains a clinical diagnosis in an appropriate setting, supported by
      serologic studies if these are available.

PMID- 15874892
TI  - Probable chronic viral encephalitis with microglial nodules in the entire brain:
      a case report with necropsy.
AB  - BACKGROUND: Chronic encephalitis has rarely been seen, probably due to its viral
      origins, which may produce the disease in healthy or immunocompromised hosts. The
      etiology and pathophysiology of these types of encephalitis have not yet been
      clarified. CASE REPORT: A 63-year-old Japanese woman with underlying multiple
      myeloma developed chronic encephalitis with fever and progressive dementia,
      bilateral mild thalamic lesions on magnetic resonance imaging, and a prolonged
      pleocytosis, normal glucose value, and elevated interleukin-6 and interferon
      gamma in the cerebrospinal fluid (CSF). The patient died of pneumonia 6 months
      after the onset of illness, and diffuse microglial nodules were found in the
      entire brain. No causative viral agents were identified by polymerase chain
      reaction and serological tests. CONCLUSIONS: The patient was presumed to have
      suffered from chronic viral encephalitis, based on clinical findings, including
      CSF and cytokine changes. Microglial nodules are observed in flavivirus group
      encephalitides, Rickettsia infections, and cytomegalovirus encephalitis in
      immunocompromised hosts. The possible pathogenesis of this rare encephalitis is
      discussed.

PMID- 15874893
TI  - Advances in endogenous morphine.

PMID- 15874894
TI  - In vivo and in vitro L-DOPA and reticuline exposure increases ganglionic morphine
      levels.
AB  - BACKGROUND: Given the presence of morphine, its metabolites and precursors, i.e.,
      reticuline, in mammalian and invertebrate tissues, it has become imperative to
      determine if exposing tissues to putative opiate alkaloid and dopamine precursors
      would result in increasing endogenous morphine levels. MATERIAL/METHODS:
      Endogenous morphine levels were determined by high performance liquid
      chromatography coupled to electrochemical detection and radioimmunoassay,
      following incubation of Mytilus edulis pedal ganglia with reticuline or L-DOPA.
      Injection of L-DOPA or reticuline into healthy animals was via the foot. RESULTS:
      Ganglia incubated in vitro with reticuline or L-DOPA for 1 hour exhibited a
      concentration and time dependent statistically significant increase in their
      endogenous morphine levels (5.0 +/- 0.47, 3.6 +/- 0.45 ng/ganglion,
      respectively). Injection of intact, healthy animals with reticuline or L-DOPA
      also results in significantly higher endogenous ganglionic morphine levels.
      CONCLUSIONS: Taken together, we show that L-DOPA is being converted to morphine,
      demonstrating that pedal ganglia can synthesize morphine from these putative
      precursors in vitro and in vivo. This is the first demonstration of morphine
      being synthesized in a normal, healthy free living animal.

PMID- 15874895
TI  - Human gliomas contain morphine.
AB  - BACKGROUND: Morphine has been found in cancer cell lines originating from human
      and animal cells. Thus, it became important to demonstrate whether or not actual
      tumours contain this opiate alkaloid. MATERIAL/METHODS: Human glioma tissues were
      biochemically treated to isolate and separate endogenous morphine via high
      pressure liquid chromatography (HPLC). The HPLC peak corresponding to an
      authentic morphine standard had its morphine level determined via radioimmune
      assay. The identity of this material was established by Q-TOF-MS analysis.
      RESULTS: Each glioma exhibited an endogenous morphine presence. Tumor extractions
      demonstrated a molecular mass of 286.14 da, identical to authentic morphine.
      Subsequent fragmentation analysis of this molecule revealed fragment masses of
      129.01 da, 183.09 da and 201.07 da, corresponding to authentic morphine
      fragments. This material was not found in any of the solutions used in the study
      nor was it present as a residual material in blank HPLC runs. CONCLUSIONS:
      Morphine is present in human gliomas, suggesting that it may exert an action that
      effects tumour physiology/pathology.

PMID- 15874896
TI  - Endogenous morphine and ACTH association in neural tissues.
AB  - BACKGROUND: Endogenous morphine and proopiomelanocortin-derived peptide-like
      molecules were identified in molluscan tissues, including the nervous system,
      supporting their ancient phylogeny. Their presence and function in "simple"
      animals, demonstrates their involvement in mechanisms underlying the stress
      response, preceding the mammalian neuroendocrine axis. MATERIAL/METHODS:
      Immunocytochemical analysis was used to study the localization of morphine- and
      adrenocorticotropic hormone (ACTH)-like material in the nervous system of
      Planorbarius corneus, Mytilus galloprovincialis, Lymnaea stagnalis and Viviparus
      ater. Acute stress experiments were performed on P. corneus and, by radioimmune
      assay, we quantified the expression of an ACTH-like peptide in control and
      stressed animals. RESULTS: We demonstrate that in mollusks the presence of a
      morphine-like compound is differentially distributed in neuronal structures
      containing an ACTH-like molecule. In P. corneus, the two immunoreactivities
      appear to be colocalized in neuronal bodies and axonal endings, suggesting a role
      in neurotransmission/neuromodulation. We also found that these molecules are
      released in the hemolymph, suggesting neuroendocrine-immunoregulatory
      communication. Comparative studies on the other mollusks gave different
      distribution pictures of the two immunoreactivities. In P. corneus, following
      experimental trauma, the levels of both the messengers increase in ganglia and
      hemolymph at different times, which can be related to their postulated roles.
      CONCLUSIONS: In mollusks more than in mammals, there is a diversified but close
      association between morphine and ACTH, both acting in a stress response possibly
      exerting reciprocal influences, suggesting that the relationship evolved in
      invertebrates and was conserved during evolution.

PMID- 15874897
TI  - Characterization of a morphine-like molecule in secretory granules of chromaffin
      cells.
AB  - BACKGROUND: Morphine and morphine-like molecules were identified in numerous
      mammalian tissues. In particularly, morphine was present in adrenal gland and in
      PC-12 cells, corresponding to the cell line derived from rat adrenal medullary
      chromaffin cells. MATERIAL/METHODS: Morphine-like compounds were isolated after a
      deproteinization followed by a reverse phase high pressure chromatography
      purification coupled to a UV detector. This alkaloid was identified using nano
      eletrospray ionization quadripole time of flight tandem mass spectrometry.
      RESULTS: We demonstrate the presence of a morphine-like molecule inside the
      bovine chromaffin cell secretory granules. This alkaloid was also detected into
      the secretion medium of primary chromaffin cells in culture following nicotinic
      stimulation. CONCLUSIONS: Our findings demonstrate that a morphine-like component
      is synthesized in chromaffin cells and secreted into the incubation medium upon
      stimulation. This finding strongly suggests that this material may be released
      from adrenal tissues in response to stressors.

PMID- 15874898
TI  - Regulation of various genes in human leukocytes acutely exposed to morphine:
      expression microarray analysis.
AB  - BACKGROUND: Previous studies from our laboratory have identified a novel mu
      opiate receptor micro(3), which is expressed in several different cell types and
      tissues including human vascular endothelial cells, leukocytes and neural
      tissues. This novel micro receptor is selective for the opiate alkaloid morphine,
      since this receptor does not bind other opioid peptides. MATERIAL/METHODS: This
      report details the acute affects of morphine exposure (1 microg/ml) to human
      leukocytes by analyzing gene expression using microarrays (Applied Biosystems).
      Robust estimation of the median fold change was used to identify candidates for
      significantly differentially expressed genes. An independent experiment using
      four same sample arrays was used to test the algorithm and to confirm the
      calculated percentage of falsely significant genes. RESULTS: Data obtained from
      this study demonstrate that acute morphine exposure differentially affected genes
      that are involved in immune function, signal transduction, cell adhesion, and
      apoptosis. CONCLUSIONS: Acute morphine exposure to human leukocytes results in
      specific and significant alterations in gene expression.

PMID- 15874899
TI  - Morphine 6beta glucuronide: fortuitous morphine metabolite or preferred
      peripheral regulatory opiate?
AB  - Morphine-6beta-glucuronide (M6G), a metabolite of morphine that the brain can
      produce, is an opiate agonist that appears to have a greater analgesic potency
      than morphine. M6G has a 1-octanol/water partition coefficient 187 times lower
      than that of morphine and M6G has a blood brain barrier permeability 57 times
      lower than morphine. The brain uptake rate however is only 32 times lower,
      suggesting that an active transport mechanism might be present. Furthermore,
      evidence for a distinct receptor for M6G also appears to be emerging. Real time
      polymerase chain reactions allowed for the discovery of single nucleotide
      polymorphisms (SNP's) in the human mu opioid receptor gene. The most common SNP
      is a substitution at base118 where A is replaced with G (A118G). This SNP has a
      decreased potency for M6G in individuals possessing it whereas the potency of
      morphine is unaffected by this SNP. The possibility that a peripheral opiate
      signaling system, using M6G and its distinct receptor, exists seems plausible.
      Taken together, if a distinct M6G signaling mechanism does exist, the fact that
      morphine can be converted into a more water soluble compound that might be more
      potent would not be an accident.

PMID- 15874900
TI  - Pain, immunity, opiate and opioid compounds and health.
AB  - We surmise that opioid peptides, i.e., methionine enkephalin, first arose during
      evolution as modulators of cellular immune function given their immune actions
      and the presence of enkelytin, a potent antibacterial peptide, and its precursor
      proenkephalin in animals 500 million years divergent in evolution. Pain probably
      emerged from this perspective because of its association with proinflammatory
      events. Endogenous morphine appears to exert positive effects on homeostasis by
      limiting the degree of excitation. Supporting this view is the fact that the mu3
      opiate receptor subtype, which is opioid peptide insensitive and morphine
      selective, is coupled to constitutive nitric oxide release, which also has this
      down regulating action in neural, immune, vascular and gastrointestinal tissues.
      Thus, morphine down regulates immune processes in addiction, an action/function
      that it appears to normally perform when the situation calls for this action and
      by so doing in this natural setting, sustains life.

PMID- 15874901
TI  - Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and
      motivation circuitries.
AB  - Evidence suggests that the placebo response is related to the tonic effects of
      constitutive nitric oxide in neural, vascular and immune tissues. Constitutive
      nitric oxide levels play a role in the modulation of dopamine outflow in the
      nigrostriatal movement and the mesolimbic and mesocortical reward and motivation
      circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may
      be an important signal molecule working at mu receptors on gamma aminobutyric
      acid B interneurons to disinhibit nigral and tegmental dopamine output. We
      surmise that placebo induced belief will activate the prefrontal cortex with
      downstream stimulatory effects on these dopamine systems as well as on
      periaqueductal grey opioid output neurons. Placebo responses in Parkinson's
      disease, depression and pain disorder may result. In addition,
      mesolimbic/mesocortical control of the stress response systems may provide a way
      for the placebo response to benefit other medical conditions.

PMID- 15874902
TI  - Mammalian morphine: de novo formation of morphine in human cells.
AB  - BACKGROUND: Morphine, the major alkaloid of opium of Papaver somniferum, is one
      of the strongest analgesic compounds known. "Endogenous morphine" has been long
      isolated and authenticated by mass spectrometry in trace amounts from animal and
      human specific tissue or fluids. The most widely accepted explanation presently
      is that morphine detected in human and animal tissue is of exogenous sources
      (e.g. dietary origin). MATERIAL/METHODS: The biosynthetic experiments were
      performed with human neurobalstoma cells (SH-SY5Y) and human pancreas carcinoma
      (DAN-G) cells. The application experiments were done in the presence of
      isotopically labeled potential precursors such as (18)O(2) and [ring-(13)C(6)]-L
      tyrosine. Benzylisoquinoline alkaloids present in mammalian cells were identified
      by GC-MS/MS. RESULTS: Growth of the SH-SY5Y cells in the presence of (18)O2 led
      to [(18)O(2)]-labeled morphine and [(18)O(2)]-labeled reticuline, each had a
      molecular mass four mass units higher than if grown in (16)O(2), indicating the
      presence of two atoms of (18)O per molecule. DAN-G cells cultured in an (18)O(2)
      atmosphere produced (S)-[ (18)O(2)]-norlaudanosoline and (S)-[ (18)O(2)]
      reticuline, each labeled with (18)O atoms at only two of the four possible
      positions. Feeding of [ring-(13)C(6)]-tyramine, (S)-[1-(13)C, N-(13)CH(3)]
      reticuline and [N-CD(3)]-thebaine to SH-SY5Y cells led each to the labeling of
      morphine, as established by GC-MS/MS. CONCLUSIONS: Taken together, morphine,
      reticuline and norlaudanosoline are unequivocally biosynthesized by cultured
      human cells. The precursors of morphine in the human cell lines were conclusively
      shown to be oxygen, tyramine, reticuline and thebaine.

PMID- 15874903
TI  - X-ray diffraction-enhanced imaging of uterine leiomyomas.
AB  - BACKGROUND: The purpose of this study was to investigate the microstructures of a
      uterine leiomyoma using a synchrotron-based imaging technique. MATERIAL/METHODS:
      The tissues of different regions of a uterine leiomyoma were imaged using X-ray
      diffraction-enhanced imaging. RESULTS: Compared with optical microscopy and
      conventional X-ray, X-ray diffraction-enhanced imaging can show not only the
      surface, but also the internal structure of organs or soft tissues with better
      contrast. Internal hyaline degeneration and the cavum of liquefied uterine
      leiomyomas are shown very clearly. Some microstructures, such as the myomatous
      burble, rupture and conglomeration of muscle fiber, and the cavum resulting from
      red degeneration, can be displayed in X-ray diffraction-enhanced images. These
      microstructures can show the developmental progress of necrosis in uterine
      leiomyomas and indicate their potential canceration. CONCLUSIONS: X-ray
      diffraction-enhanced imaging can clearly show internal microstructures of uterine
      leiomyomas, making the complex procedure of doing this with a large number of
      pathology slices avoidable.

PMID- 15874904
TI  - Advances in digital technology and orthodontics: a reference to the Invisalign
      method.
AB  - BACKGROUND: Increased aesthetic demands during orthodontic treatment resulted in
      several treatment alternatives. However, the need to avoid conventional fixed
      orthodontic appliances led, with the use of computer-aided scanning, imaging, and
      manufacturing technology, to the development of new therapy concepts such as
      Invisalign. MATERIAL/METHODS: The Invisalign orthodontic technique involves a
      series of clear removable appliances and has been applied to correct a variety of
      malocclusions. RESULTS: The Invisalign method is an aesthetic orthodontic option
      for many patients, but it is suited mainly to adults or adolescents who have a
      fully erupted dentition and it has its indications and limitations. It handles
      simple to moderate non-extraction alignments better than mild to moderate
      extraction cases. The aligners are clear and therefore aesthetically ideal for
      the patient; they are comfortable to wear and, as they are removable, they
      provide simplicity of care and better oral hygiene. They also allow the
      evaluation of treatment options in detail before beginning treatment by using a
      virtual treatment model. It is also important to point out that this method has
      some disadvantages, which are associated with patient compliance, limited control
      over specific tooth movements, and additional documentation time. CONCLUSIONS:
      The Invisalign concept is an aesthetic alternative in orthodontic treatment, with
      advantages and disadvantages. It can be utilized to treat simple to moderate
      alignment cases, especially in adults, and serves as an additional part of the
      armamentarium of the orthodontist.

PMID- 15874905
TI  - Resource loss and stress-related disease: is there a link?
AB  - Clinical and pre-clinical evidences prove that among many individuals
      experiencing stress, only a sub-population will progress to disease. Thus,
      understanding the causes of individual differences and the consequences of
      variation in vulnerability is of major importance. The aim of this review is to
      shed light on this issue by discussing results obtained on a new naturalistic
      model of chronic psychosocial stress in male mice. Resident/intruder pairs of
      mice lived in continuous sensory contact and physically interacted daily. Four
      categories were identified: resident dominant, resident subordinate, intruder
      dominant, and intruder subordinate. Of these groups, I will discuss here the
      results obtained in the resident subordinate group. A resident subordinate mouse
      owned a resource, i.e. a territory, before an intruder mouse won the social
      competition and became the dominant in that territory. Resident subordinates
      showed a unique profile of immuno-endocrine alterations and metabolic disorders,
      suggesting that the loss of relevant resources, such as territory, can be one key
      factor determining why only certain stress-exposed individuals ultimately show
      malignancy and psychopathologies. An analysis of the human and animal literature
      suggests this conclusion to be true for a variety of pathologies linked to
      chronic stress exposure.

PMID- 15874906
TI  - Is angiotensin-II an endogenous pro-inflammatory molecule?
AB  - Angiotensin-II, a product of angiotensin converting enzyme (ACE) action,
      regulates vascular tone, stimulates the release of pro-inflammatory cytokines,
      activates NFkappaB, increases oxidant stress, and suppresses nitric oxide
      synthesis. Thus, angiotensin-II is pro-inflammatory in nature. Hence, increase in
      ACE activity and the concentrations of angiotensin-II initiate and perpetuate
      inflammation. Since ACE is present in many tissues including: the uterus,
      placenta, vascular tissue, heart, brain, adrenal cortex and kidney, leukocytes,
      alveolar macrophages, peripheral monocytes, neuronal cells and epididymal cells,
      this suggests that angiotensin-II may have a role in atherosclerosis, congestive
      cardiac failure, stroke, bipolar disorder, schizophrenia, dementia, Alzheimer's
      disease, psoriasis, atopic and non-atopic dermatitis, eczema, several acute and
      chronic inflammatory diseases, and cancer, conditions in which inflammation is
      known to play a significant role. This suggests that ACE inhibitors and/or
      angiotensin-II receptor blockers could be of significant benefit in the
      management of these conditions. Alternatively, structural analogues of presently
      available ACE inhibitors and angiotensin-II receptor blockers could be developed
      such that they are not only useful in the treatment of hypertension and CHF but
      also possess anti-inflammatory actions.

PMID- 15874907
TI  - The effect of socioeconomic factors on incidence, stage at diagnosis and survival
      of cutaneous melanoma.
AB  - Melanoma represents a significant and growing public health burden worldwide,
      especially in Caucasian populations. The purpose of this review is to summarize
      the literature on the relationship between socioeconomic status (SES) and
      incidence, stage at diagnosis and survival from melanoma. Although differences
      across countries exist on the relationship of SES to specific behaviors or risk
      factors, our principal findings are: melanoma is more common in high SES than in
      low SES populations; and low SES populations present with later stages at
      diagnosis and experience worse survival rates from melanoma than high SES
      populations. Potential explanations for these findings are that high SES
      individuals may have a higher susceptibility and exposure (e.g., risk behaviors)
      for developing melanoma, and low SES individuals may have less access to
      educational campaigns and screening examinations and effective treatment. These
      differences reflect a disparity in melanoma outcomes across diverse SES
      populations in many countries.

PMID- 15874908
TI  - Cytological aspects of rat mammary cancer therapy with soluble tumor-associated
      antigens and anticancer drugs.
AB  - Some cytological aspects of rat mammary cancer therapy with soluble tumor
      associated antigens (sTAA- p66 and p51) and the anticancer drug cyclophosphamide
      (CPA) are analyzed. Vaccination with sTAA results in a significant increase in
      the areas related to the production of T and B cells in the white pulp (germinal
      center and PALS) and in the marginal zone of the spleen. sTAA stimulate the
      production of CD8+ lymphocytes inside the tumors and in bone marrow, and of CD8+
      thymocytes in the medulla of the thymus. Treatment of rats with CPA decreases the
      activity of lymph cells in tumors, especially of CD4+ lymphocytes. In the spleen,
      CPA decreases the size of areas related to the production of B and T cells. In
      the bone marrow, CPA affects the process of myelogenesis and causes significant
      substitution of cellular components with fatty tissue. The combined treatment
      with CPA and sTAA increases the number of lymph cells and the apoptotic index in
      tumors, and restored the rate of B cells producing in the spleen. Similar effect
      was observed in lymph nodes with accumulation of B lymphocytes in the primary and
      secondary follicles, and of T lymphocytes in the paracortical zone. In the
      thymus, CPA alone or in combination with sTAA repairs the inhibitor effect of a
      carcinogen on synthesis of CD4+ and CD8+ thymocytes. In combined using with CPA,
      sTAA activate the B- and T-lymphocyte production in the host's immune system and
      decrease the toxic side-effects of a drug.

PMID- 15874916
TI  - Endovascular treatment of popliteal artery aneurysms: results of a prospective
      cohort study.
AB  - OBJECTIVE: Popliteal artery aneurysms can be treated endovascularly with less
      perioperative morbidity compared with open repair. To evaluate suitability of the
      endovascular technique and the clinical results of this treatment, we analyzed a
      prospective cohort of consecutive popliteal aneurysms referred to a tertiary
      university vascular center. METHODS: All popliteal artery aneurysms between June
      1998 and June 2004 that measured >20 mm in diameter were analyzed for
      endovascular repair. Anatomic suitability was based largely on quality of the
      proximal and distal landing zone as determined by angiography. Endovascular
      treatment was performed by using a nitinol-supported expanded
      polytetrafluoroethylene lined stent graft introduced through the common femoral
      artery. RESULTS: We analyzed 67 aneurysms in 57 patients. Ten aneurysms (15%)
      were excluded from endovascular repair, or from any repair at all, for various
      reasons. The remaining 57 (85%) were treated endovascularly, of which 5 were
      treated emergently for acute ischemia. During a mean 24-month follow-up, 12 stent
      grafts (21%) occluded. Primary and secondary patency rates were 80% and 90% at 1
      year, and 77% and 87% at 2 years of follow-up. Postoperative treatment with
      clopidogrel proved to be the only significant predictor for success. CONCLUSIONS:
      Endovascular repair of a popliteal artery aneurysm is feasible. Changes in the
      material used and the addition of clopidogrel may improve patency rates.

PMID- 15874918
TI  - To what extent has endovascular aneurysm repair influenced abdominal aortic
      aneurysm management in the state of Illinois?
AB  - PURPOSE: This study was performed using population-based data to determine the
      changing trends in the techniques for abdominal aortic aneurysm (AAA) repair in
      the state of Illinois during the past 9 years and to examine the extent to which
      endovascular aneurysm repair (EVAR) has influenced overall AAA management.
      METHODS: All records of patients who underwent AAA repair (1995 to 2003
      inclusive) were retrieved from the Illinois Hospital Association COMPdata
      database. The outcome as determined by in-hospital mortality was analyzed
      according to intervention type (open vs EVAR) and indication (elective repair vs
      ruptured AAA). Data were stratified by age, gender, and hospital type (university
      vs community setting) and then analyzed using both univariate (chi 2 , t tests)
      and multivariate (stepwise logistic regression) techniques. RESULTS: Between 1995
      and 2003, 14,517 patients underwent AAA repair (85% for elective and 15% for
      ruptured AAA). The average age was 71.4 +/- 7.9 years, and 76% were men. For
      elective cases, open repair was performed in 86% and EVAR in 14%; and for
      ruptured cases, open repair in 97% and EVAR in 3%. Elective EVAR was associated
      with lower in-hospital mortality compared with open repair regardless of age. No
      differences were observed with age after either type of repair for a ruptured
      aneurysm. Men had a lower in-hospital mortality compared with women for open
      repair of both elective and ruptured aneurysms. For EVAR, the mortality of an
      elective repair was lower in men, but there was no difference after a ruptured
      AAA. In men, the difference in mortality between elective open repair and EVAR
      was significant; the type of institution did not influence outcome. Patients >80
      years of age had a higher mortality after open repair for both elective and
      ruptured AAA and after EVAR of a ruptured AAA. The average length of stay was 9.9
      days for open elective repair, 13.1 days after open repair of a ruptured AAA, and
      3.6 days for EVAR. The independent predictors of higher in-hospital mortality
      were female gender, age >80 years, diagnosis (ruptured vs open), and procedure
      (open vs EVAR). The year of the procedure and type of hospital (university vs
      community) were not predictive of outcome. CONCLUSIONS: EVAR has had a
      significant impact on AAA management in Illinois over a relatively short time
      period. In this population-based review, EVAR was associated with a significantly
      decreased in-hospital mortality and length of stay. Octogenarians had higher
      mortality after both types of repair, with the exception of elective EVAR.

PMID- 15874919
TI  - Prediction of altered endograft path during endovascular abdominal aortic
      aneurysm repair with the Gore Excluder.
AB  - OBJECTIVE: During endovascular abdominal aortic aneurysm (AAA) repair (EVAR), the
      rapid deployment of the Gore Excluder endograft may be associated with anatomic
      shortening of the endograft path. This shortened path may result in coverage of
      the hypogastric artery origin or overly conservative graft length selection that
      may lead to unnecessary extensions. We quantified the degree of path alteration
      with this endograft and developed an algorithm to predict it. METHODS:
      Preoperative and postoperative three-dimensional (3D) computed tomographic (CT)
      scans were evaluated for 50 consecutive patients with Gore Excluder endografts by
      using 21 anatomic measurements and 6 calculated indices. Measurements were
      evaluated as if only 3D lumen centerline measurements were available, rather than
      complete 3D computer-aided measurement and "virtual graft" simulation. Tortuosity
      was quantitated from the renal artery to the hypogastric origin, using the
      difference between a straight line and the lumen centerline. RESULTS: The
      endograft was deployed successfully in all cases. The graft end points were
      typically quite close to the preoperative plan: mean renal artery-to-graft
      distance was within 2.0 +/- .5 mm, and the limb end point-to-hypogastric origin
      differed by an average of only 1.8 +/- 1.6 mm. Although accurate in most cases,
      the actual graft path shortened 1 cm or more relative to the centerline in 11% of
      limbs. On univariate analysis, determinants of alteration of >1 cm in the graft
      deployment path were (1) aortoiliac tortuosity (renal-to-hypogastric artery, P <
      .002), (2) the degree of planned graft rotation (73% of cases altered >10 mm were
      in the rotated position, P < .05), and (3) the insertion side (73% of alterations
      >or=10 mm were ipsilateral to the main device, P < .05). On multivariate
      analysis, the renal-to-hypogastric artery tortuosity index (RHTI) was significant
      ( P < .004), and device type and rotation approached significance ( P < .08). We
      developed a classification scheme based on RHTI to predict the risk of alteration
      of the graft path >or=1 cm (low risk, 0%; medium risk, 10%; high risk, 25%) and
      an algorithm to predict the degree of alteration of the anatomy that reduced the
      number of cases shortening >or=1 cm to zero. CONCLUSIONS: The graft deployment
      path will be altered significantly in a minority of cases with the Gore Excluder
      endograft, but this can cause hypogastric occlusion or other problems. Anatomic
      shortening is predictable from morphologic features such as tortuosity, graft
      insertion side, and rotation. We developed an algorithm based on a tortuosity
      index that quantitates the risk and degree of shortening associated with
      endograft deployment.

PMID- 15874920
TI  - Size and location of thrombus in intact and ruptured abdominal aortic aneurysms.
AB  - PURPOSE: This study compared the volume and morphology of intraluminal thrombus
      (ILT) in intact and ruptured abdominal aortic aneurysms (AAAs). METHODS: ILT
      volume in 67 intact AAAs and in 31 ruptured AAAs was assessed by using computed
      tomography (CT) angiography to measure the major and minor diameter of the outer
      wall and lumen of AAA as outlined by contrast at multiple sites. ILT thrombus
      morphology was recorded by AutoCAD 2000 software. Four equidistant images traced
      from the CT scan were recorded along the length of AAA. Thrombus volume was
      categorized as anterior-eccentric if the calculated area of thrombus was greater
      anteriorly, posterior-eccentric if greater posteriorly, eccentric-equal if the
      difference between the anterior and posterior thrombus was <or=10%, and no
      thrombus. RESULTS: Patients were well matched for age, gender, and other
      demographic variables except hypertension, which was significantly higher in
      ruptured AAA group ( P = .018). Ruptured AAAs were larger in diameter compared
      with intact AAAs (7.3 +/- 1.7 cm vs 6.0 +/- 1.2 cm, P = .0002). ILT volume was
      greater in ruptured AAAs (148.9 +/- 90.4 cm 3 ) compared with intact AAAs (92.1
      +/- 75.6 cm 3 , P = .0031). However, the ILT volume/aneurysm volume ratio was
      similar in the two groups (0.49 +/- 0.19 in intact AAAs, 0.47 +/- 0.18 in
      ruptured AAAs; P = .8). Two patients in intact AAA group and three patients in
      the ruptured AAA group did not have ILT. Eccentric thrombus was present in 65 of
      67 in the intact group and in 28 of 31 in the ruptured AAA group. Eccentric
      anterior thrombus was predominant in both groups (46 of 67 in intact AAAs; 14 of
      31 in ruptured AAAs). Thrombus location was statistically similar in both groups
      ( P = .101). CONCLUSION: Ruptured AAAs are larger in diameter and have a greater
      volume of thrombus compared with intact AAAs. However, there was no difference in
      the thrombus volume/aneurysm volume ratio in the two groups. In both intact and
      ruptured AAA groups, the thrombus was usually anterior and eccentric.

PMID- 15874921
TI  - Endovascular repair of thoracic aortic lesions with the Zenith TX1 and TX2
      thoracic grafts: intermediate-term results.
AB  - PURPOSE: This prospective study was designed to assess the technical success and
      outcome after patients with thoracic aortic pathology at high risk for
      conventional therapy were treated with the Zenith TX1 and TX2 endovascular graft.
      METHODS: Between 2001 and 2004, patients at high risk for conventional surgical
      therapy presenting with chronic aortic dissections, thoracic aneurysms, or
      aortobronchial or aortoesophageal fistulas were treated with a single- or
      multiple-piece endovascular grafts. Surgical modification of proximal or distal
      fixation sites was performed when necessary to establish adequate regions for
      device landing zones. Follow-up studies included radiographic evaluation before
      discharge and at 1, 6, 12, and 24 months. Aortic morphologic characteristics were
      determined by using three-dimensional imaging studies and centerline of flow
      measurements. Statistical analyses were performed with Kaplan Meier analysis to
      assess survival, factors predictive of poor outcome, and morphologic changes,
      including sac shrinkage. RESULTS: A total of 100 patients (42% women) were
      treated, including 81 aneurysms, 15 aortic dissections (with aneurysms), 2
      patients with fistulous connections (1 aortobronchial and 1 aortoesophageal), 1
      subclavian artery aneurysm, and 1 aortic rupture. Mean follow-up and aneurysm
      size were 14 months and 62 mm, respectively. Most patients (55%) had undergone
      prior aortic aneurysm repair. Surgical modifications were required to create
      adequate implantation sites in 29% patients, including 14 elephant trunk/arch
      reconstructions, 18 carotid-subclavian bypasses, and 4 visceral vessel bypasses.
      Iliac conduits were required in 19 patients. Overall mortality was 17%, and
      aneurysm-related mortality was 14% at 1 year. Sac regression (>5 mm maximum
      diameter decrease) was observed in 52% and 56% at 12 and 24 months. Growth was
      noted in one patient (1.6%) at 12 months. Endoleaks were detected in eight
      patients (8.5%) at 30 days and three patients (6%) at 12 months. Secondary
      interventions were required in 15 patients. Migration (>10 mm) of the proximal or
      distal stent was noted in three patients (6%) (two proximal and one distal), none
      of which required treatment or resulted in an adverse event. CONCLUSIONS:
      Acceptable intermediate-term outcomes have been achieved in the treatment of high
      risk patients in the setting of both favorable and challenging anatomic
      situations with these devices. The complexity of the patient population, in
      contrast to endovascular infrarenal repair, attests to the differences in the
      pathophysiology aortic disease in the anatomic beds.

PMID- 15874922
TI  - Surgical treatment of atypical aortic coarctation complicating Takayasu's
      arteritis--experience with 33 cases over 44 years.
AB  - PURPOSE: This study was conducted to evaluate the long-term outcomes of surgical
      treatment for atypical aortic coarctation due to Takayasu's arteritis and to
      elucidate the factors that affected outcome. METHODS: The outcomes of surgical
      treatment for atypical aortic coarctation complicating Takayasu's arteritis in 33
      consecutive patients over the previous 44 years at our institution were reviewed
      retrospectively. Preoperatively, 29 patients had coarctation proximal to the
      renal arteries and hypertension in the upper half of the body. Four hospital
      deaths occurred, and the remaining 29 patients were followed from 0.5 to 42.0
      years (median, 17.9 years). The impacts of several risk factors on survival as
      well as cardiac and vascular events were analyzed. RESULTS: Among 27 initial
      survivors who had hypertension preoperatively, 15 did not show normalization of
      blood pressure. The overall cumulative survival and event-free survival rate at
      20 years were 62.3% and 58.4%, respectively. Serious long-term complications were
      anastomotic aneurysms, congestive heart failure, cerebrovascular accident, graft
      deterioration, abdominal aortic aneurysms, and renal failure. Among several risk
      factors analyzed, only the presence of postoperative hypertension had an effect
      on event-free survival. CONCLUSIONS: The long-term survival after surgery for
      atypical aortic coarctation was satisfactory. However, our study showed that
      complications associated with cardiovascular system or the operation could occur
      at any time after surgery; thus, life-long follow-up is mandatory. Further, the
      absence of normalization of blood pressure after surgery was a poor prognostic
      factor. Our results demonstrate the need for an intimate preoperative evaluation
      of renal and carotid artery lesions, which often coexist and may also cause
      secondary hypertension, to fully manage hypertension by surgery.

PMID- 15874923
TI  - Perioperative beta-blockade (POBBLE) for patients undergoing infrarenal vascular
      surgery: results of a randomized double-blind controlled trial.
AB  - OBJECTIVE: To assess whether a pragmatic policy of perioperative beta-blockade,
      with metoprolol, reduced the 30-day cardiovascular morbidity and mortality and
      reduced the length of hospital stay in average patients undergoing infrarenal
      vascular surgery. METHODS: This was a double-blind randomized placebo-controlled
      trial that occurred in vascular surgical units in four UK hospitals. Participants
      were 103 patients without previous myocardial infarction who had infrarenal
      vascular surgery between July 2001 and March 2004. Interventions were oral
      metoprolol (50 mg twice daily, supplemented by intravenous doses when necessary)
      or placebo from admission until 7 days after surgery. Holter monitors were kept
      in place for 72 hours after surgery. RESULTS: Eighty men and 23 women (median
      age, 73 years) were randomized, 55 to metoprolol and 48 to placebo, and 97 (94%)
      underwent surgery during the trial. The most common operations were aortic
      aneurysm repair (38%) and distal bypass (29%). Intraoperative inotropic support
      was required in 64% and 92% of patients in the placebo and metoprolol groups,
      respectively. Within 30 days, cardiovascular events occurred in 32 patients,
      including myocardial infarction (8%), unstable angina (9%), ventricular
      tachycardia (19%), and stroke (1%). Four (4%) deaths were reported.
      Cardiovascular events occurred in 15 (34%) and 17 (32%) patients in the placebo
      and metoprolol groups, respectively (unadjusted relative risk, 0.94; 95%
      confidence interval, 0.53-1.66; adjusted [for age, sex, statin use, and aortic
      cross-clamping] relative risk, 0.87; 95% confidence interval, 0.48-1.55). Time
      from operation to discharge was reduced from a median of 12 days (95% confidence
      interval, 9-19 days) in the placebo group to 10 days (95% confidence interval, 8
      12 days) in the metoprolol group (adjusted hazard ratio, 1.71; 95% confidence
      interval, 1.09-2.66; P < .02). CONCLUSIONS: Myocardial ischemia was evident in a
      high proportion (one third) of the patients after surgery. A pragmatic regimen of
      perioperative beta-blockade with metoprolol did not seem to reduce 30-day
      cardiovascular events, but it did decrease the time from surgery to discharge.

PMID- 15874924
TI  - Association of neutrophils and future cardiovascular events in patients with
      peripheral artery disease.
AB  - OBJECTIVE: We hypothesized that higher neutrophil counts are associated with an
      increased incidence of major adverse cardiovascular events (MACE) in patients
      with clinically advanced atherosclerosis. METHODS: We prospectively studied 398
      patients (233 men; median age, 69 years) with symptomatic peripheral artery
      disease who were admitted to the inpatient ward of the angiology department of a
      tertiary care university hospital in a cohort study. Total and differential white
      blood cell (WBC) counts were obtained, and patients were followed for MACE,
      defined as myocardial infarction, percutaneous coronary interventions, coronary
      artery bypass grafting, stroke, carotid revascularization, and death. RESULTS:
      During a median follow-up of 20 months, 140 MACE occurred in 105 patients (26%).
      Multivariate Cox proportional hazards analysis was used to assess the association
      of differential WBC count parameters (in tertiles) with MACE and their
      interrelation with traditional cardiovascular risk factors and other parameters
      of inflammation. Patients with neutrophil counts >5.8 G/L (upper tertile)
      exhibited an increased adjusted risk for all MACE (hazards ratio [HR], 1.83; P =
      .017), death (HR, 3.39; P = .010), and the composite of myocardial infarction,
      stroke, and death (HR, 2.20; P = . 012) compared with patients in the lower
      tertile (<4.4 G/L), independently of traditional cardiovascular risk factors and
      levels of high-sensitivity C-reactive protein. Only neutrophils, but not
      eosinophils, basophils, monocytes, lymphocytes, or the total WBC count showed a
      significant association with cardiovascular outcome. CONCLUSION: In patients with
      peripheral artery disease, neutrophil counts in the upper tertile (>5.8 G/L)
      indicate a substantially increased risk for major adverse cardiovascular events,
      adding to the prognostic information of traditional atherothrombotic risk factors
      and other parameters of inflammation.

PMID- 15874925
TI  - Prediction of early cerebral outcome by transcranial Doppler monitoring in
      carotid bifurcation angioplasty and stenting.
AB  - OBJECTIVE: The outcomes of carotid angioplasty and stenting (CAS) are, in
      addition to patient baseline characteristics, highly dependent on the safety of
      the endovascular procedure. During the successive stages of CAS, transcranial
      Doppler (TCD) monitoring of the middle cerebral artery was used to assess the
      association of cerebral embolism and hemodynamic changes with transient
      (amaurosis fugax and transient ischemic attack) and persistent (minor and major
      stroke) cerebral deficits, and death. METHODS: By use of a prospectively
      completed database of 550 patients, the association of various TCD emboli and
      velocity variables with periprocedural cerebral outcome <or=7 days was evaluated
      by univariable and multivariable logistic regression analyses in combination with
      receiver operating characteristic (ROC) curve analyses. The impact of basic
      patient characteristics, such as age, sex, preprocedural cerebral symptoms, and
      ipsilateral carotid endarterectomy before CAS was also evaluated. RESULTS: We
      observed 36 patients with amaurosis fugax (n = 6; 1.1%) or transient ischemic
      attack (n = 30; 5.4%), 1 patient (0.2%) with an ipsilateral retinal infarct, and
      21 patients with minor (n = 15; 2.7%) or major (n = 6; 1.1%) stroke,
      respectively. Five patients (0.9%) died. Multiple showers of microemboli (>5) at
      postdilation after stent deployment (odds ratio [OR] 2.6, 95% confidence interval
      [CI], 1.3 to 5.1), particulate macroembolus (OR, 27.0; 95% CI, 4.5 to 157), and
      massive air embolism (OR, 51.4; 95% CI, 5.4 to 492), as well as angioplasty
      induced asystole and prolonged hypotension with a >70% reduction of middle
      cerebral artery blood flow velocities (OR, 6.4; 95% CI, 2.3 to 17.8) were
      independently associated with cerebral deficits. The ROC area of this model was
      0.72. Of the patient characteristics, only preprocedural cerebral ischemia (OR,
      5.0; 95% CI, 2.4 to 10.4) was associated with outcome. Adding this patient
      characteristic to the model, the area under the ROC curve increased to 0.80.
      CONCLUSIONS: In CAS, in addition to such obviously adverse events as particulate
      macroembolism and massive air embolism, multiple microemboli (>5 showers) at
      postdilation after stent deployment and angioplasty-induced asystole and
      hypotension with a significant reduction of middle cerebral artery blood flow
      velocities are associated with periprocedural cerebral deficits. In combination
      with the presence of preprocedural cerebral symptoms, these four TCD monitoring
      variables reasonably differentiate between patients with and without adverse
      cerebral outcome. TCD monitoring provides insight into the pathogenesis of CAS
      related adverse cerebral events.

PMID- 15874926
TI  - Relationship between objective measures of peripheral arterial disease severity
      to self-reported quality of life in older adults with intermittent claudication.
AB  - OBJECTIVES: The aim of this study was to determine the relation between
      functional measures of peripheral arterial disease (PAD) severity with both
      disease-specific and generic self-reported health-related quality-of-life (HR
      QOL) measures, as well as the relation between the two types of HR-QOL measures.
      METHODS: This was a cross-sectional observation of participants from the
      community and primary care or vascular surgery clinics in an academic Veterans
      Administration medical center. Eighty patients with symptomatic Fontaine stage II
      PAD provided physiologic measures and self-response questionnaires. Objective
      measures included the ankle-brachial index (ABI), time to maximum claudication
      pain on a graded exercise test, and a 6-minute floor-walking distance. Self
      reports included the Walking Impairment Questionnaire (WIQ), a disease-specific
      HR-QOL measure and the Medical Outcomes Study (MOS) Short-Form 36 (SF-36), a
      generic HR-QOL measure. RESULTS: Patients (mean age 70 +/- 8 [+/- SD] and 85%
      men) exhibited moderate-to-severe PAD by objective measures of ABI (0.65 +/-
      0.19) and time in minutes to maximal claudication on a graded exercise test (7:54
      +/- 4:58). Significant correlations were found between these measures and the WIQ
      distance, MOS-Physical Function, and MOS-Role Limitations due to physical
      dysfunction. The SF-36 and the WIQ subscales were significantly correlated.
      CONCLUSION: In older PAD patients with intermittent claudication, objective
      measures of disease severity are correlated with a self-reported, disease
      specific and generic HR-QOL.

PMID- 15874927
TI  - Carotid endarterectomy impairs blood pressure homeostasis by reducing the
      physiologic baroreflex reserve.
AB  - OBJECTIVE: To assess the impact of carotid endarterectomy on blood pressure
      homeostasis and baroreflex function, with particular reference to the presence or
      absence of significant contralateral carotid artery disease, we conducted a
      prospective study in 80 patients with symptomatic extracranial carotid disease
      undergoing carotid endarterectomy in a regional teaching hospital over 2 years.
      METHODS: Patients were divided into two groups: the control group (n = 37) had no
      significant contralateral carotid disease; patients in the diseased group (n =
      23) had either >70% stenosis or occlusion of the contralateral carotid artery.
      Seventeen patients with abnormal heart rhythms, poor quality recordings, or with
      intermediate degrees of contralateral carotid stenosis were excluded. Three
      patients who had previously undergone contralateral carotid endarterectomy were
      separately evaluated. Atheromatous plaque was removed from carotid lumen and the
      baroreflex mechanism received direct intraoperative stimulation before and after
      carotid endarterectomy. The main outcome measures were (1) the hemodynamic
      response to the carotid endarterectomy, baroreflex sensitivity, and operating set
      point (the resting blood pressure, which the baroreflex mechanism maintains)
      before and after removal of the atheromatous plaque, and (2) the responsiveness
      of the ipsilateral baroreceptor mechanism to direct stimulation. The impact of
      the presence of contralateral carotid stenosis on these variables was also
      evaluated. RESULTS: Patients in the two groups were comparable for preoperative
      demographic, medication, and hemodynamic variables. Carotid endarterectomy led to
      a rise in mean arterial pressure from 81.3 +/- 3.9 mm Hg to 103.5 +/- 4.6 mm Hg (
      P < .00001) and from 87.6 +/- 4.3 mm Hg to 94.0 +/- 4.5 mm Hg ( P < .003) in the
      diseased and control groups, respectively. The magnitude of blood pressure
      response was significantly greater in the diseased group than in the control
      group ( P < .00001). This hypertensive shift was not accompanied by the expected
      fall in heart rate. Direct baroreflex stimulation prior to carotid endarterectomy
      caused a significantly greater response in the diseased group, suggesting
      sensitization of the ipsilateral carotid baroreceptor in the presence of
      contralateral carotid disease. Furthermore, the baroreflex response was
      obliterated after endarterectomy. There were significant reductions in baroreflex
      sensitivity and a hypertensive shift in the operating set point, the magnitude of
      which was significantly greater in patients with contralateral carotid disease.
      CONCLUSIONS: Carotid endarterectomy impairs blood pressure homeostasis through
      surgical destruction of the ipsilateral carotid baroreflex mechanism. Patients
      with contralateral carotid stenosis have a reduced baroreflex reserve and show
      greater baroreflex dysfunction and hemodynamic instability after endarterectomy.
      These patients are at greater risk of postendarterectomy complications and should
      be monitored closely.

PMID- 15874928
TI  - Contemporary management of wartime vascular trauma.
AB  - OBJECTIVE: The treatment of wartime injuries has led to advances in the diagnosis
      and treatment of vascular trauma. Recent experience has stimulated a reappraisal
      of the management of such injuries, specifically assessing the effect of
      explosive devices on injury patterns and treatment strategies. The objective of
      this report is to provide a single-institution analysis of injury patterns and
      management strategies in the care of modern wartime vascular injuries. METHODS:
      From December 2001 through March 2004, all wartime evacuees evaluated at a single
      institution were prospectively entered into a database and retrospectively
      reviewed. Data collected included site, type, and mechanism of vascular injury;
      associated trauma; type of vascular repair; initial outcome; occult injury;
      amputation rate; and complication. Liberal application of arteriography was used
      to assess these injuries. The results of that diagnostic and therapeutic
      approach, particularly as it related to the care of the blast-injured patient,
      are reviewed. RESULTS: Of 3057 soldiers evacuated for medical evaluation, 1524
      (50%) sustained battle injuries. Known or suspected vascular injuries occurred in
      107 (7%) patients, and these patients comprised the study group. Sixty-eight
      (64%) patients were wounded by explosive devices, 27 (25%) were wounded by
      gunshots, and 12 (11%) experienced blunt traumatic injury. The majority of
      injuries (59/66 [88%]) occurred in the extremities. Nearly half (48/107) of the
      patients underwent vascular repair in a forward hospital in Iraq or Afghanistan.
      Twenty-eight (26%) required additional operative intervention on arrival in the
      United States. Vascular injuries were associated with bony fracture in 37% of
      soldiers. Twenty-one of the 107 had a primary amputation performed before
      evacuation. Amputation after vascular repair occurred in 8 patients. Of those, 5
      had mangled extremities associated with contaminated wounds and infected grafts.
      Sixty-seven (63%) patients underwent diagnostic angiography. The most common
      indication was mechanism of injury (42%), followed by abnormal examination (33%),
      operative planning (18%), or evaluation of a repair (7%). CONCLUSIONS: This
      interim report represents the largest analysis of US military vascular injuries
      in more than 30 years. Wounding patterns reflect past experience with a high
      percentage of extremity injuries. Management of arterial repair with autologous
      vein graft remains the treatment of choice. Repairs in contaminated wound beds
      should be avoided. An increase in injuries from improvised explosive devices in
      modern conflict warrants the more liberal application of contrast arteriography.
      Endovascular techniques have advanced the contemporary management and proved
      valuable in the treatment of select wartime vascular injuries.

PMID- 15874929
TI  - Patterns of saphenous reflux in women with primary varicose veins.
AB  - OBJECTIVE: Varicose veins have been linked to great saphenous vein (GSV) reflux
      and in particular, with reflux at the saphenofemoral junction (SFJ). Early stages
      of disease, however, may be associated with limited, localized reflux in segments
      of the GSV and/or small saphenous vein (SSV). Ultrasound mapping of saphenous
      veins was performed to determine patterns of GSV and SSV reflux in women with
      simple, primary varicose veins. METHODS: Ultrasound mapping was performed
      prospectively in 590 extremities of 326 women with varicose veins (CEAP C 2
      class) but without edema, skin changes, or ulcers (C 3 to C 6 ). Average age was
      42 +/- 13 (SD) years (range, 8 to 87). Patterns of GSV and SSV reflux, obtained
      in the upright position, were classified as I: perijunctional, originating from
      the SFJ or saphenopopliteal junction (SPJ) tributaries into the GSV or SSV; II:
      proximal, from the SFJ or SPJ to a tributary or perforating vein above the level
      of the malleoli; III: distal, from a tributary or perforating vein to the
      paramalleolar GSV or SSV; IV: segmental, from a tributary or perforating vein to
      another tributary or perforating vein above the malleoli; V; multisegmental, if
      two or more distinct refluxing segments were detected; and VI: diffused,
      involving the entire GSV or SSV from the SFJ or SPJ to the malleoli. RESULTS:
      Reflux was detected in 472 extremities (80%): 100 (17%) had reflux in both the
      GSV and SSV, 353 (60%) had GSV reflux only, and 19 (3%) had SSV reflux only, for
      a total prevalence of 77% at the GSV and 20% at the SSV. The most common pattern
      of GSV reflux was segmental (types IV and V) in 342 (58%) of 590; either one
      segment in 213 (36%) or more than one segment with competent SFJ in 99 (17%), or
      incompetent SFJ in 30 (5%), followed by distal GSV reflux (type III) in 65 (11%),
      proximal GSV reflux (type II) in 32 (5%), diffused throughout the entire GSV
      (type VI) in 10 (2%), and perijunctional (type I) in 4 (<1%). GSV refluxing
      segments were noted in the SFJ in 72 (12%) and in the thigh in 220 (37%), and leg
      (or both) in 345 (58%). CONCLUSIONS: The high prevalence of reflux justifies
      ultrasound mapping of the saphenous veins in women with primary varicose veins.
      Correction of SFJ reflux, however, may be needed in <or=12% of the extremities,
      and only about one third CEAP C2 limbs may require treatment of a refluxing GSV
      in the thigh.

PMID- 15874930
TI  - Experience of temporary inferior vena cava filters inserted in the perinatal
      period to prevent pulmonary embolism in pregnant women with deep vein thrombosis.
AB  - OBJECTIVE: We placed temporary inferior vena cava filters to prevent pulmonary
      thromboembolism in patients with deep vein thrombosis (DVT) who were presumed to
      have an increased risk of pulmonary embolism in the perinatal period. These
      experiences of using temporary inferior vena cava filters in pregnant women are
      reported. METHODS: We reviewed 11 patients with DVT who underwent placement of a
      temporary inferior vena cava filter and delivered in our hospital between 1998
      and 2004. All of the filters were placed at the suprarenal inferior vena cava
      before delivery. During filter placement, anticoagulant therapy was routinely
      performed, and we stopped the administration of anticoagulant agents intrapartum.
      RESULTS: No complications occurred at filter insertion or during placement. No
      symptomatic pulmonary thromboembolism occurred during or after delivery. All of
      the filters were successfully removed, one of which was exchanged for a permanent
      filter because the temporary filter captured a large thrombus. CONCLUSION:
      Intrapartum temporary inferior vena cava filters may reduce the incidence of
      pulmonary thromboembolism in pregnancy with DVT. Temporary inferior vena cava
      filters appear to be safe for pregnant women.

PMID- 15874931
TI  - Influence of type II endoleak volume on aneurysm wall pressure and distribution
      in an experimental model.
AB  - OBJECTIVE(S): We have previously shown that type II endoleak size is a predictor
      of aneurysm growth after aortic endografting. To better understand this
      observation, we investigated the influence of endoleak size on pressure
      transmitted to the aneurysm wall and its distribution within the aneurysm sac.
      METHODS: In an ex vivo model, an artificial aneurysm sac was incorporated within
      a mock circulation comprised of rubber tubing and a pulsatile pump. Three strain
      gauge pressure transducers were placed in the aneurysm wall at different
      locations, including the site of maximum aneurysm diameter. The aneurysm was
      filled with either human aneurysm thrombus or dough that mimicked thrombus and
      simulated type II endoleaks of varying volumes (1 to 10 mL) were created.
      Aneurysm wall pressure (AWP) measurements were recorded at mean arterial
      pressures (MAPs) of 60, 80, and 100 mm Hg. Correlation coefficients ( r ) and
      analysis of variance were used to assess the relationship between endoleak volume
      and AWP. RESULTS: Increasing endoleak volume '3 cm 3 resulted in proportionally
      increased AWP at all levels of MAP and at all sites, with highest pressures
      recorded at the site of the maximum aneurysm diameter (r = 0.83 when MAP = 100 mm
      Hg; r = 0.85 when MAP = 80 mm Hg; r = 0.88 when MAP = 60 mm Hg; P < .001). AWP
      plateaued when the endoleak volume was >3 cm 3 . Pressure distribution within the
      sac was not uniform. Although the difference was within +/-10%, statistically
      significant higher AWPs were observed at the site of maximum aneurysm diameter (P
      <.001). AWP also correlated with MAP. CONCLUSIONS: Increasing type II endoleak
      volume results in proportionally higher AWP, which is greatest at the site of
      maximum aneurysm diameter. This study confirms the clinical observation that type
      II endoleak volume and MAP may be important predictors of aneurysm expansion.
      CLINICAL RELEVANCE: Our experimental model of a type II endoleak revealed that
      endoleak size is a significant factor that influences the magnitude of pressure
      transmission into the aneurysm wall. Increasing volume of the endoleak nidus was
      associated with proportionally higher aneurysm sac pressures. This mechanism may,
      in fact, account for the increased risk of aneurysm expansion observed in our
      clinical experience, thereby suggesting the need for more aggressive surveillance
      and possibly earlier intervention for patients with larger endoleaks.

PMID- 15874932
TI  - Iliac fixation length and resistance to in-vivo stent-graft displacement.
AB  - PURPOSE: Migration of endovascular stent grafts has been related to the security
      of proximal device fixation to the aortic neck. This study evaluated the
      importance of iliac fixation in preventing longitudinal in vivo device
      displacement of a modular, externally supported stent graft. METHODS:
      Experimental ovine infrarenal aneurysms (n = 8) were treated with a fully
      supported, modular, bifurcated stent graft (AneuRx, Medtronic, Santa Rosa,
      Calif). Minimum iliac fixation length (1 cm) was used in four animals and iliac
      extender modules were used to achieve maximum iliac fixation in four animals.
      Suture anastomosis of bifurcated polyester grafts to the infrarenal aorta served
      as controls (n = 8). Aortic grafts were displaced in vivo by applying downward
      traction to a guidewire that was passed over the iliac flow divider and brought
      out both femoral arteries. The displacement force needed to initiate stent-graft
      migration was recorded and compared with the force needed to disrupt the sutured
      anastomosis. RESULTS: There was no difference in animal weight (88.8 +/- 2.5 kg
      vs 87.5 +/- 2.9 kg), aortic neck diameter (12.7 +/- 0.9 mm vs 13.4 +/- 1.1 mm),
      aortic neck length (23.2 +/- 0.9 mm vs 21.8 +/- 2.4 mm), experimental aneurysm
      size (24.7 +/- 1.1 mm vs 24.2 +/- 2.0 mm), or iliac artery diameter (9.0 +/- 1.5
      mm vs 9.3 +/- 0.5 mm) among the groups. Iliac fixation length was 31.0 +/- 0.3 mm
      in the maximum iliac fixation group and 11 +/- 0.25 mm in the minimum fixation
      group (P < .0001). Peak displacement force to initiate migration was 30.2 +/- 5.5
      N (range, 25 to 38) in animals with maximum iliac fixation compared with 18.1 +/-
      3.7 N (range, 13 to 21) in those with minimum fixation (P = .01). The force
      needed to disrupt the control surgical anastomosis was 40.6 +/- 7.5 N (range, 31
      to 50) (P < .01). CONCLUSIONS: Maximizing iliac fixation length increases the
      longitudinal in vivo force needed to displace a fully supported stent graft by
      67%. This suggests that increasing iliac fixation length may reduce the long-term
      risk of migration in patients undergoing endovascular aneurysm repair.

PMID- 15874933
TI  - Urokinase-induced smooth muscle cell responses require distinct signaling
      pathways: a role for the epidermal growth factor receptor.
AB  - OBJECTIVE: Urokinase plasminogen activator (uPA) a key serine protease during
      remodeling, is capable of inducing both smooth muscle cell migration and
      proliferation. However, the signals that produce these responses are poorly
      understood. METHODS: Early passage rat aortic arterial smooth muscle cells were
      cultured in vitro and standard assays of DNA synthesis ([ 3 H]thymidine
      incorporation), cell proliferation (manual cell counting), and migration (linear
      wound assay and Boyden chamber) were used to study the cells responses to uPA.
      Activation of the mitogen-activated protein kinases (MAPK), extracellular signal
      regulated kinase 1/2 (ERK1/2), p38 MAPK , Akt, MAP kinase/ERK kinase (MEK1/2),
      MAP kinase kinase (MKK)3/6, and epidermal growth factor receptor (EGFR) in
      response to uPA was assayed by Western blot analysis for the phosphorylated form
      of each kinase. These assays were repeated in the presence of the Galphai
      inhibitor pertussis toxin (PTx, 100 ng/mL), the Ras inhibitor manumycin A (MA, 10
      microM), the phosphatidyl-inositol 3' kinase (PI3K) inhibitor wortmannin (WN, 1
      microM), the EGFR inhibitor AG1478 (AG, 10 nM), the MEK1 inhibitor PD98059 (PD,
      10 microM), the p38 MAPK inhibitor SB203580 (SB, 10 microM), and the plasmin
      inhibitors aprotinin and epsilon-aminocaproic acid. RESULTS: uPA induced a
      twofold increase in smooth muscle cell migration and increased smooth muscle cell
      DNA synthesis and proliferation. The ERK1/2 and p38 MAPK inhibitors PD98059 (PD)
      and SB203580 (SB) blocked cell proliferation, but only PD blocked cell migration.
      Although uPA-induced phosphorylation of both ERK1/2 and p38 MAPK was blocked by
      Galphai inhibition, inhibition of PI3K and Ras decreased the uPA-induced
      phosphorylation of ERK1/2 but not p38 MAPK . Activation of MEK1/2 was abrogated
      by inhibitors of Galphai and Ras, but not by PI3K inhibition. In contrast,
      activation of MKK3/6 was abrogated by inhibition of Galphai, but not by Ras or
      PI3K inhibition. uPA induced time-dependent phosphorylation of EGFR, which was
      dependent on plasmin activity. Inhibition of EGFR reduced both ERK1/2 and p38
      MAPK activation. uPA activation of PI3K and MKK3/6 was EGFR-dependent and that of
      MEK1 was EGFR-independent. CONCLUSION: uPA induces smooth muscle cell
      proliferation through ERK1/2- and p38 MAPK -mediated pathways. Migration appears
      to be dependent on ERK1/2 activity alone. Activation of EGFR appears to be
      required. The differential activation of pathways for ERK1/2 and p38 MAPK by uPA
      allows for two distinct biologic responses that both require tyrosine kinase
      receptor transactivation. CLINICAL RELEVANCE: Elevated urokinase-like plasminogen
      activator (uPA) and decreased plasminogen activator inhibitor-1 (PAI-1) levels
      are predictors for restenosis. Matrix remodeling and smooth muscle cell responses
      are integrally linked. Changes in smooth muscle cell migration and proliferation
      are dependent on the extracellular matrix environment in which they are encased.
      Proteases such as uPA can effect smooth muscle cells and alter the matrix; their
      activity is controlled by a series of inhibitors (eg, PAI-1). The balance of
      activation and inhibition forms the basis of the proteolytic thermostat in the
      vessel wall. Understanding the biology of the proteolytic thermostat will allow
      for structured therapeutic interventions to control restenosis and thus improve
      patient care and avoid secondary interventions. Our study demonstrates that uPA
      is capable of inducing separate responses through more than one signaling
      pathway, in part, by transactivation of a nearby receptor for the unrelated
      ligand epidermal growth factor receptor (EGFR). Blockade of EGFR can inhibit both
      cell migration and proliferation induced by uPA. This is the first description of
      cross talk between uPA and EGFR in vascular smooth muscle cells. Targeting a
      pivotal receptor such as EGFR, which can be transactivated by both G-protein
      coupled receptors and receptor tyrosine kinases, is an attractive molecular
      target to control restenosis.

PMID- 15874934
TI  - Survivin expression is up-regulated in vascular injury and identifies a distinct
      cellular phenotype.
AB  - OBJECTIVES: The healing response to vascular injury is characterized by
      neointimal thickening. Proliferation and phenotypic transformation of vascular
      smooth muscle cells (SMCs) have been implicated in this process. We sought to
      investigate the role of survivin, a dual regulator of cell proliferation and
      apoptosis, in lesion formation after diverse forms of vascular injury. METHODS:
      Rabbits underwent either carotid interposition vein grafting (n = 17) or
      bilateral femoral balloon injury (BI; n = 29); some in the BI group were placed
      on a high-cholesterol diet. A subset of BI arteries were treated with local
      adenoviral gene delivery of a survivin dominant negative-mutant (AdT34A) versus
      vector or saline controls. Survivin expression in vessels was analyzed by
      quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and by
      immunohistochemistry (IHC), which also included markers of SMC differentiation.
      Specimens of human tissue including failed lower extremity bypass grafts and
      carotid plaque were also examined. RESULTS: RT-PCR and IHC demonstrated increased
      survivin expression in all experimental models, colocalizing at early times with
      proliferating and alpha-actin-expressing cells but was largely absent in mature,
      contractile SMCs. Delivery of AdT34A after BI attenuated neointimal hyperplasia.
      CONCLUSION: These studies provide strong evidence supporting a role for survivin
      in the cellular response to vascular injury. CLINICAL RELEVANCE: The regulation
      of cell proliferation, death, and phenotype after vascular interventions remains
      incompletely understood. We investigated the role of the inhibitor of apoptosis
      protein survivin in diverse models of vascular injury. The results suggest that
      survivin is an important modulator of the generalized vascular injury response
      and may represent a relevant target for therapies targeting intimal hyperplasia.

PMID- 15874935
TI  - Adipocyte-derived cytokine resistin causes endothelial dysfunction of porcine
      coronary arteries.
AB  - OBJECTIVE: Resistin, a novel adipocyte-derived cytokine, is involved in the
      development of insulin resistance and diabetes mellitus. In this study, we
      determined whether resistin could affect vasomotor function, oxidative stress,
      and endothelial nitric oxide synthase (eNOS) expression in porcine coronary
      arteries. METHODS: Porcine coronary arteries were treated with resistin or
      antioxidant seleno-L-methionine (SeMet). Vasomotor function was studied by using
      a myograph system. Levels of superoxide anion (O 2 - ) were detected by the
      lucigenin-enhanced chemiluminescence method. The eNOS mRNA and protein levels
      were determined by real-time polymerase chain reaction and immunohistochemistry,
      respectively. Culture of isolated porcine coronary artery endothelial cells
      (PCAECs) was also included. RESULTS: Endothelium-dependent relaxation in response
      to bradykinin was reduced by 15% and 30% for the rings treated with 10 and 40
      ng/mL of resistin, respectively, as compared with controls ( P < .05).
      Endothelium-independent relaxation in response to sodium nitroprusside (SNP) was
      also reduced by 11% after treatment with 40 ng/mL of resistin ( P < .05). The O 2
      - level was increased in the 40 ng/mL resistin-treated vessels by 88% as compared
      with controls ( P < .05). SeMet reversed these effects. The eNOS mRNA levels in
      PCAEC cultures treated with resistin (10 and 40 ng/mL) were decreased by 27% and
      55%, respectively ( P < .05) and by 39% in the endothelial cells purified from
      porcine coronary artery rings after treatment with 40 ng/mL of resistin ( P <
      .05). Immunoreactivity of eNOS in the resistin-treated vessel rings was also
      substantially reduced. CONCLUSIONS: Resistin reduces the endothelium-dependent
      and endothelium-independent vasorelaxation. This effect is associated with
      increased superoxide radical production, decreased eNOS expression, and is
      effectively reversed by the antioxidant SeMet. CLINICAL RELEVANCE: Obesity has
      been considered to be an independent risk factor for coronary artery disease and
      other vascular lesions. Resistin is a newly discovered adipocyte-derived
      cytokine, and its plasma levels are increased in obese individuals. However, it
      is not clear whether resistin could directly contribute to vascular disease
      formation. This study showed that resistin can cause endothelial dysfunction in
      porcine coronary arteries through oxidative stress and down-regulation of eNOS.
      Thus, this study may suggest a new mechanism of obesity-associated vascular
      disease and that antioxidants may effectively prevent vascular disease in obese
      individuals.

PMID- 15874936
TI  - Vascular endothelial growth factor-C promotes vasculogenesis, angiogenesis, and
      collagen constriction in three-dimensional collagen gels.
AB  - OBJECTIVE: Neovascularization, angiogenesis, and collagen constriction are
      essential for wound healing. We tested whether vascular endothelial growth factor
      C (VEGF-C) can promote collagen constriction, capillary sprouting (angiogenesis),
      and invasion/migration of bone marrow-derived endothelial progenitor cells into
      collagen (vasculogenesis). METHODS: We used a recently characterized three
      dimensional collagen matrix assay with either monolayers of human dermal
      microvascular endothelial cells (HMVECs) or bone marrow-derived endothelial
      progenitor cells (BMD EPCs), obtained from Tie-2 LacZ transgenic mice, overlaid
      with an acellular layer and then a cellular layer of collagen embedded with
      fibroblasts, that were nontransduced or transduced with either LacZ adenoviral
      vector (Ad5) or VEGF-C/Ad5. The ability of VEGF-C to enhance fibroblast-mediated
      collagen constriction was measured, and gels overlying HMVECs or BMD EPCs were co
      cultured, harvested, and assayed for HMVEC migration, sprouting, and capillary
      like formation; gels containing BMD EPCs were assayed for EPC invasion/migration
      into the collagen extracellular matrix. RESULTS: VEGF-C significantly increased
      collagen constriction and formation of capillary-like structures with true lumina
      (P < .05) assessed by von Willebrand factor and VEGF receptor-2 immunoassaying.
      VEGF-C induced a significant increase in HMVEC migration, tubular polarization,
      and branching sprouts associated with a significant up-regulation of membrane
      type 1 matrix metalloproteinase (MT1-MMP) ( P < .05). Fibroblasts were necessary
      to support BMD-EPC invasion/migration from the monolayer into the collagen.
      Moreover, fibroblasts overexpressing VEGF-C significantly enhanced EPC
      invasion/migration ( P < .05) into the extracellular matrix by two-fold, and this
      effect could not be achieved with equivalent levels of exogenous VEGF-C in the
      absence of fibroblasts. The addition of a soluble VEGF-C competitor protein only
      partially inhibited these responses, reducing the EPCs by three-fold, but
      significant numbers of EPCs still invaded/migrated into the extracellular matrix,
      suggesting that other fibroblast-specific signals also contribute to the
      vasculogenic response. CONCLUSION: Fibroblast-specific expression of VEGF-C
      promotes collagen constriction by fibroblasts and enhances microvascular
      endothelial cell migration, branching, and capillary sprouting in association
      with up-regulating MT1-MMP expression. Fibroblasts are necessary for BMD EPC
      invasion/migration into collagen, and their overexpression of VEGF-C enhances
      this fibroblast-mediated vasculogenic effect. Collectively, these findings
      suggest a role for VEGF-C in multiple biologic steps required for wound healing
      (angiogenesis, vasculogenesis, and collagen constriction). CLINICAL RELEVANCE:
      Ischemic wound healing remains an unsolved problem with no previously identified
      molecular target for therapeutic intervention. This study demonstrates that VEGF
      C overexpression by fibroblasts stimulates multiple biologic processes known to
      impact wound healing, such as collagen constriction, capillary sprouting, and EPC
      invasion and migration through extracellular matrix. Most ischemic wounds fail to
      heal and frequently lead to major limb amputation. Available cytokine ointments
      are ineffective, and revascularization is often not technically feasible. Even
      when these procedures are accomplished, many ischemic wounds frequently still do
      not heal because of multifactorial tissue level impairments in the fibroblastic
      and neovascularization responses at the wound base. Our findings identify an
      important role for two novel tissue level targets, dermis-derived fibroblasts and
      VEGF-C, in collagen constriction, angiogenesis, and postnatal vasculogenesis from
      BMD EPCs. Thus the findings are particularly relevant to the unsolved clinical
      problem of ischemic wound healing.

PMID- 15874937
TI  - Esophageal fistula after endovascular treatment in a type B aortic dissection of
      the descending thoracic aorta.
AB  - We report a type B aortic dissection treated with stenting of the descending
      thoracic aorta that subsequently developed an ischemic necrosis of the esophagus
      with a posterior mediastinum abscess. The surgical treatment consisted of an
      extra-anatomic bypass to revascularize the supra-aortic trunks and the distal
      abdominal aorta through a middle sternal laparotomy, the resection of the
      thoracic aorta, and the drainage of the mediastinal abscess. Despite this
      aggressive surgical approach and an initial favorable postoperative course, the
      patient suddenly died 3 weeks later, likely from a rupture of the aortic stump.

PMID- 15874938
TI  - Bronchoesophageal fistula after endovascular repair of ruptured aneurysm of the
      descending thoracic aorta.
AB  - Aortoesophageal fistula secondary to thoracic aneurysm is rare and is usually
      fatal without prompt surgical intervention. A 79-year-old man with significant
      comorbidities and previous cancer surgery was admitted on an emergency basis
      because of the suspicion of a ruptured thoracic aortic aneurysm. Computed
      tomographic scan followed by angiography demonstrated a ruptured thoracic
      aneurysm with aortoesophageal fistula. An endovascular stent graft repair was
      performed with successful exclusion of both aneurysm and fistula. On
      postoperative day 6, dyspnea and an isolated episode of hemoptysis occurred.
      Endoscopy revealed the presence of a bronchoesophageal fistula, which
      necessitated double exclusion of the esophagus and feeding jejunostomy. At 6
      months, clinical, bronchoscopic, and computed tomographic scan follow-up showed
      complete sealing of the aneurysm and resolution of the bronchoesophageal fistula.
      At 9 months, the patient was still alive but refused to undergo substernal
      gastric bypass in an attempt to restore oral feeding. Endovascular repair seems
      promising as an emergent and palliative treatment of aortoesophageal fistula. To
      the best of our knowledge, this is the first case in which a bronchoesophageal
      fistula developed after successful endovascular repair of aortoesophageal
      fistula. The pathogenesis of this complications remains unclear.

PMID- 15874939
TI  - Delayed treatment and late complications of a traumatic arteriovenous fistula.
AB  - An 18-year-old soldier had a gunshot wound to his left thigh during the Mexican
      Civil War (1910-1917). He presented with persistent bright red bleeding. His
      wound was treated by compression. A few years after the injury, he noticed a
      thrill, large varicose veins, limb swelling, and skin changes. A plain film
      showed an 8 x 10-cm midthigh mass. After a bullfighting incident, the
      pseudoaneurysm ruptured. Because of increased bulk and discomfort, the patient
      agreed 3 years later to be treated. Angiography showed a chronically obstructed
      femoral artery and vein. A 3000-mL hematoma was evacuated. This case illustrates
      the long-term sequelae of an arteriovenous fistula. This report describes a 51
      year delay of treatment for causes unrelated to diagnosis. To our knowledge, this
      case is the longest delay in treatment of an arteriovenous fistula and its
      complications reported in the literature.

PMID- 15874940
TI  - Recurrent carotid stenosis after angioplasty and stenting.

PMID- 15874941
TI  - Nomenclature of the veins of the lower limb: extensions, refinements, and
      clinical application.
AB  - The relative deficiency of the official Terminologia Anatomica with regard to the
      veins of the lower limbs was responsible for a nonuniform anatomic nomenclature
      in the clinical literature. In 2001, an International Interdisciplinary Committee
      updated and refined the official Terminologia Anatomica regarding the veins of
      the lower limbs. Recommendations for terminology were included in an updating
      document that appeared in the Journal of Vascular Surgery (2002;36:416-22). To
      enhance further the use of a common scientific language, the committee worked on
      the present document, which includes (1) extensions and refinements regarding the
      veins of the lower limbs; (2) the nomenclature of the venous system of the
      pelvis; (3) the use of eponyms; and (4) the use of terms and adjectives of
      particular importance in clinical vascular anatomy.

PMID- 15874942
TI  - Masters and commanders.

PMID- 15874943
TI  - The ethics of administrative credentialing.
AB  - A vascular surgeon has practiced in the same community for more than 20 years,
      holding privileges at the two largest local general hospitals. She is widely
      respected and admired by patients and fellow physicians in all specialties, and
      her results are consistently good. Recently, the board of directors at the
      hospital that has been the source of 80% of her case referrals hired a notorious
      slash-and-burn management firm to improve the balance sheet. The new chief
      executive officer (CEO) installed an information technology system that can
      provide management with physician-specific figures on costs and reimbursements.
      The management consultants identified the 10% of physicians with the worst
      cost/reimbursement ratios over the preceding 5 years and persuaded the board of
      directors to order their clinical privileges withdrawn. Our seasoned surgeon
      learns that she is among the targeted group. Is there an ethical issue here, and,
      if so, how should she respond?

PMID- 15874944
TI  - Regarding "Practical applications of hemodynamic effect of intermittent pneumatic
      compression of the leg after infrainguinal arterial bypass grafting".

PMID- 15874945
TI  - Monitoring of the hypoglossal nerve during general anesthesia.

PMID- 15874946
TI  - Abdominal aortic aneurysm prefers to rupture on a dim day.

PMID- 15874949
TI  - Regarding "Deep vein thrombosis after radiofrequency ablation of greater
      saphenous vein: a word of caution".

PMID- 15874951
TI  - Regarding "Dorsalis pedis artery true aneurysm due to atherosclerosis: case
      report and literature review".

PMID- 15874955
TI  - The pediatric rescue airway.

PMID- 15874956
TI  - A case study in metabolic acidosis induced by inhalation.

PMID- 15874958
TI  - Long-distance air medical transport of a neonate suffering from a complete AV
      canal combined with a hypoplastic left ventricle.

PMID- 15874964
TI  - Hospital helipads and the Emergency Medical Treatment and Active Labor Act.

PMID- 15874966
TI  - Chasing ambulance safety.

PMID- 15874965
TI  - Critical issues facing the air medical transport community. The 2003 Air Medical
      Leadership Congress survey.

PMID- 15874967
TI  - Hospital-division operations: Metro Life Flight.

PMID- 15874968
TI  - Taking your crew resource management temperature.

PMID- 15874969
TI  - Helicopter ambulance system and injury reporting in Sweden's mass media: a
      content analysis of the Swedish News Agency from 2000-2004.

PMID- 15874972
TI  - Cardiac arrest/cardiopulmonary resuscitation augments cell-mediated immune
      function and transiently suppresses humoral immune function.
AB  - Immune system activation has implications for cerebrovascular health, but little
      is known about the function of the immune system after a major cerebrovascular
      event, such as cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Cardiac
      arrest and cardiopulmonary resuscitation damages the hippocampus, an important
      component of the hypothalamic-pituitary-adrenal (HPA) axis, and alterations in
      HPA axis activity can affect immune function. We tested the hypothesis that
      CA/CPR (approximately 8 mins) would cause HPA axis dysregulation and alter the
      delayed type hypersensitivity (DTH) response to antigenic challenge. We also
      assessed the primary and secondary antibody response of mice exposed to CA/CPR.
      Of the mice exposed to CA/CPR, half had brains protected by hypothermia to
      isolate the effects of the CA/CPR procedure from the effects of CA/CPR-induced
      neuronal damage. Cardiac arrest and cardiopulmonary resuscitation-induced
      neuronal damage resulted in a persistent elevation of blood corticosterone
      concentration and a concomitant augmentation of the DTH response to antigenic
      challenge. Furthermore, immune activation before CA/CPR decreased survival after
      global ischemia. These data highlight the potential impact of neuronal damage on
      cell-mediated immune function and the role of humoral immune activation in
      outcome after global ischemia.

PMID- 15874973
TI  - Cocaine- and amphetamine-regulated transcript (CART) peptide: a vasoactive role
      in the cerebral circulation.
AB  - Cocaine- and amphetamine-regulated transcript (CART) peptides are known to be
      involved in the stress response and have been implicated in the regulation of the
      cardiovascular system. We evaluated the direct vasoactive properties of CART in
      the cerebral circulation and its potential mechanisms of action. Penetrating
      cerebral arterioles, isolated from male Sprague-Dawley rats, were cannulated
      using a concentric micropipette setup, pressurized and perfused. The vascular
      response to intraluminal and extraluminal CART peptide was characterized. The
      endothelium dependence of this response was assessed by means of the endothelial
      light-dye injury model. The nonspecific endothelin receptor antagonist PD-145065,
      the ET(A)-specific antagonist BQ-123, the ET(B)-specific antagonist BQ-788, and
      the inhibitor of endothelin-converting enzyme phosphoramidon were used to
      characterize the involvement of the endothelin pathway in the vascular response
      to CART peptide. Extraluminal and intraluminal application of CART peptide (0.1
      nm to 1 micromol/L) evoked a long-lasting dose-dependent constriction of isolated
      penetrating cerebral arterioles to approximately 80% of resting myogenic tone.
      Disruption of the endothelium by the endothelial light/dye injury model resulted
      in the abolition of this response (P<0.05). Extraluminal administration of PD
      145065, BQ-123, and phosphoramidon blocked the constriction response to CART
      peptide (P<0.01). The ET(B) antagonist, BQ-788, did not alter the constriction
      response to CART peptide. Cocaine- and amphetamine-regulated transcript peptide
      is a potent vasoconstrictor in the cerebral circulation. Its direct vasoactive
      properties are endothelium-dependent and are mediated by ET(A), not ET(B),
      endothelin receptors.

PMID- 15874974
TI  - Actin redistribution underlies the sparing effect of mild hypothermia on
      dendritic spine morphology after in vitro ischemia.
AB  - Brain hypothermia is at present the most effective neuroprotective treatment
      against brain ischemia in man. Ischemia induces a redistribution of proteins
      involved in synaptic functions, which is markedly diminished by therapeutic
      hypothermia (33 degrees C). Dendritic spines at excitatory synapses are motile
      and show both shape changes and rearrangement of synaptic proteins as a
      consequence of neuronal activity. We investigated the effect of reduced
      temperature (33 degrees C and 27 degrees C compared with 37 degrees C), on spine
      motility, length and morphology by studying the distribution of GFP-actin before,
      during and after induction of in vitro ischemia. Because high-concentration actin
      filaments are located inside spines, dissociated hippocampal neurons (7-11 DIV)
      from transgenic mice expressing GFP-actin were used in this study. The movement
      of the spines and the distribution of GFP-actin were recorded using time-lapse
      fluorescence microscopy. Under normal conditions rapid rearrangement of GFP-actin
      was seen in dendritic spines, indicating highly motile spines at 37 degrees C.
      Decreasing the incubation temperature to 33 degrees C or 27 degrees C,
      dramatically reduces actin dynamics (spine motility) by approximately 50% and
      70%, respectively. In addition, the length of the spine shaft was reduced by 20%.
      We propose that decreasing the temperature from 37 degrees C to 33 degrees C
      during ischemia decreases the neuronal actin polymerization rate, which reduces
      spine calcium kinetics, disrupts detrimental cell signaling and protects neurons
      against damage.

PMID- 15874976
TI  - Rapid quantitative measurement of CMRO(2) and CBF by dual administration of (15)O
      labeled oxygen and water during a single PET scan-a validation study and error
      analysis in anesthetized monkeys.
AB  - Cerebral blood flow (CBF) and rate of oxygen metabolism (CMRO(2)) may be
      quantified using positron emission tomography (PET) with (15)O-tracers, but the
      conventional three-step technique requires a relatively long study period,
      attributed to the need for separate acquisition for each of (15)O(2), H(2)(15)O,
      and C(15)O tracers, which makes the multiple measurements at different
      physiologic conditions difficult. In this study, we present a novel, faster
      technique that provides a pixel-by-pixel calculation of CBF and CMRO(2) from a
      single PET acquisition with a sequential administration of (15)O(2) and
      H(2)(15)O. Experiments were performed on six anesthetized monkeys to validate
      this technique. The global CBF, oxygen extraction fraction (OEF), and CMRO(2)
      obtained by the present technique at rest were not significantly different from
      those obtained with three-step method. The global OEF (gOEF) also agreed with
      that determined by simultaneous arterio-sinus blood sampling (gOEF(A-V)) for a
      physiologically wide range when changing the arterial PaCO(2) (gOEF=1.03gOEF(A
      V)+0.01, P<0.001). The regional values, as well as the image quality were
      identical between the present technique and three-step method for CBF, OEF, and
      CMRO(2). In addition, a simulation study showed that error sensitivity of the
      present technique to delay or dispersion of the input function, and the error in
      the partition coefficient was equivalent to that observed for three-step method.
      Error sensitivity to cerebral blood volume (CBV) was also identical to that in
      the three-step and reasonably small, suggesting that a single CBV assessment is
      sufficient for repeated measures of CBF/CMRO(2). These results show that this
      fast technique has an ability for accurate assessment of CBF/CMRO(2) and also
      allows multiple assessment at different physiologic conditions.

PMID- 15874975
TI  - Minocycline confers early but transient protection in the immature brain
      following focal cerebral ischemia-reperfusion.
AB  - The incidence of neonatal stroke is high and currently there are no strategies to
      protect the neonatal brain from stroke or reduce the sequelae. Agents capable of
      modifying inflammatory processes hold promise. We set out to determine whether
      delayed administration of one such agent, minocycline, protects the immature
      brain in a model of transient middle cerebral artery (MCA) occlusion in 7-day-old
      rat pups. Injury volume in minocycline (45 mg/kg/dose, beginning at 2 h after MCA
      occlusion) and vehicle-treated pups was determined 24 h and 7 days after onset of
      reperfusion. Accumulation of activated microglia/macrophages, phosphorylation of
      mitogen-activated protein kinase (MAPK) p38 in the brain, and concentrations of
      inflammatory mediators in plasma and brain were determined at 24 h. Minocycline
      significantly reduced the volume of injury at 24 h but not 7 days after transient
      MCA occlusion. The beneficial effect of minocycline acutely after reperfusion was
      not associated with changed ED1 phenotype, nor was the pattern of MAPK p38
      phosphorylation altered. Minocycline reduced accumulation of IL-1beta and CINC-1
      in the systemic circulation but failed to affect the increased levels of IL
      1beta, IL-18, MCP-1 or CINC-1 in the injured brain tissue. Therefore, minocycline
      provides early but transient protection, which is largely independent of
      microglial activation or activation of the MAPK p38 pathway.

PMID- 15874977
TI  - Fear and rambling at NASA.

PMID- 15874978
TI  - In pursuit of systems.

PMID- 15874979
TI  - Pesticide results help China edge transgenic rice towards market.

PMID- 15874980
TI  - Hubble rescue mission gears up despite shuttle setback.

PMID- 15874981
TI  - Academics stress licence threat to US science.

PMID- 15874982
TI  - Rethink on review leaves researchers out in the cold.

PMID- 15874983
TI  - US bungled investigation into weapons research in Iraq.

PMID- 15874984
TI  - Arctic trends scrutinized as chilly winter destroys ozone.

PMID- 15874985
TI  - Free genome databases finally defeat Celera.

PMID- 15874986
TI  - Hikes in surface ozone could suffocate crops.

PMID- 15874988
TI  - Labs on a chip: meet the stripped down rat.

PMID- 15874989
TI  - Hotwire my heart.

PMID- 15874990
TI  - Debate to be had on best practice in mentoring.

PMID- 15874991
TI  - DNA barcoding a useful tool for taxonomists.

PMID- 15874992
TI  - Guidelines reduce the risk of brain-scan shock.

PMID- 15875001
TI  - Evolutionary biology: ghost of speciation past.

PMID- 15875002
TI  - Developmental biology: morphogens hitch a greasy ride.

PMID- 15875004
TI  - Planetary science: Saturn's retrograde renegade.

PMID- 15875005
TI  - Reproductive biology: fatty link to fertility.

PMID- 15875006
TI  - Materials science: a hard look at glass.

PMID- 15875007
TI  - Cell biology: sterol sensor comes up for air.

PMID- 15875009
TI  - Botany: specialized bird perch aids cross-pollination.
AB  - Birds may hover over or perch on flowers when feeding on nectar, and this assists
      cross-pollination if they then visit other plants. Here we investigate the
      curious sterile inflorescence axis of the South African Cape endemic 'rat's tail'
      plant (Babiana ringens, Iridaceae), whose function--unlike in other bird
      pollinated plants--is exclusively to provide a perch for foraging birds. We find
      that this structure promotes the plant's mating success by causing the malachite
      sunbird (Nectarinia famosa), its main pollinator, to adopt a position ideal for
      the cross-pollination of its unusual ground-level flowers.

PMID- 15875011
TI  - Biochemistry: a cadmium enzyme from a marine diatom.
AB  - The ocean biota contains a vast reservoir of genomic diversity. Here we present
      the sequence and preliminary characterization of a protein that is a cadmium
      containing carbonic anhydrase from the marine diatom Thalassiosira weissflogii.
      The existence of a cadmium enzyme in marine phytoplankton may indicate that there
      is a unique selection pressure for metalloenzymes in the marine environment, and
      our discovery provides a long-awaited explanation for the nutrient-like behaviour
      of cadmium in the oceans.

PMID- 15875013
TI  - Lipoprotein particles are required for Hedgehog and Wingless signalling.
AB  - Wnt and Hedgehog family proteins are secreted signalling molecules (morphogens)
      that act at both long and short range to control growth and patterning during
      development. Both proteins are covalently modified by lipid, and the mechanism by
      which such hydrophobic molecules might spread over long distances is unknown.
      Here we show that Wingless, Hedgehog and glycophosphatidylinositol-linked
      proteins copurify with lipoprotein particles, and co-localize with them in the
      developing wing epithelium of Drosophila. In larvae with reduced lipoprotein
      levels, Hedgehog accumulates near its site of production, and fails to signal
      over its normal range. Similarly, the range of Wingless signalling is narrowed.
      We propose a novel function for lipoprotein particles, in which they act as
      vehicles for the movement of lipid-linked morphogens and
      glycophosphatidylinositol-linked proteins.

PMID- 15875014
TI  - Compositional maps of Saturn's moon Phoebe from imaging spectroscopy.
AB  - The origin of Phoebe, which is the outermost large satellite of Saturn, is of
      particular interest because its inclined, retrograde orbit suggests that it was
      gravitationally captured by Saturn, having accreted outside the region of the
      solar nebula in which Saturn formed. By contrast, Saturn's regular satellites
      (with prograde, low-inclination, circular orbits) probably accreted within the
      sub-nebula in which Saturn itself formed. Here we report imaging spectroscopy of
      Phoebe resulting from the Cassini-Huygens spacecraft encounter on 11 June 2004.
      We mapped ferrous-iron-bearing minerals, bound water, trapped CO2, probable
      phyllosilicates, organics, nitriles and cyanide compounds. Detection of these
      compounds on Phoebe makes it one of the most compositionally diverse objects yet
      observed in our Solar System. It is likely that Phoebe's surface contains
      primitive materials from the outer Solar System, indicating a surface of cometary
      origin.

PMID- 15875015
TI  - Saturn's moon Phoebe as a captured body from the outer Solar System.
AB  - The orbital properties of Phoebe, one of Saturn's irregular moons, suggest that
      it was captured by the ringed planet's gravitational field rather than formed in
      situ. Phoebe's generally dark surface shows evidence of water ice, but otherwise
      the surface most closely resembles that of C-type asteroids and small outer Solar
      System bodies such as Chiron and Pholus that are thought to have originated in
      the Kuiper belt. A close fly-by of Phoebe by the Cassini-Huygens spacecraft on 11
      June 2004 (19 days before the spacecraft entered orbit around Saturn) provided an
      opportunity to test the hypothesis that this moon did not form in situ during
      Saturn's formation, but is instead a product of the larger protoplanetary disk or
      'solar nebula'. Here we derive the rock-to-ice ratio of Phoebe using its density
      combined with newly measured oxygen and carbon abundances in the solar
      photosphere. Phoebe's composition is close to that derived for other solar nebula
      bodies such as Triton and Pluto, but is very different from that of the regular
      satellites of Saturn, supporting Phoebe's origin as a captured body from the
      outer Solar System.

PMID- 15875016
TI  - Manipulating spin and charge in magnetic semiconductors using superconducting
      vortices.
AB  - The continuous need for miniaturization and increase in device speed drives the
      electronics industry to explore new avenues of information processing. One
      possibility is to use electron spin to store, manipulate and carry information.
      All such 'spintronics' applications are faced with formidable challenges in
      finding fast and efficient ways to create, transport, detect, control and
      manipulate spin textures and currents. Here we show how most of these operations
      can be performed in a relatively simple manner in a hybrid system consisting of a
      superconducting film and a paramagnetic diluted magnetic semiconductor (DMS)
      quantum well. Our proposal is based on the observation that the inhomogeneous
      magnetic fields of the superconducting film create local spin and charge textures
      in the DMS quantum well, leading to a variety of effects such as Bloch
      oscillations and an unusual quantum Hall effect. We exploit recent progress in
      manipulating magnetic flux bundles (vortices) in superconductors and show how
      these can create, manipulate and control the spin textures in DMSs.

PMID- 15875012
TI  - The genome of the social amoeba Dictyostelium discoideum.
AB  - The social amoebae are exceptional in their ability to alternate between
      unicellular and multicellular forms. Here we describe the genome of the best
      studied member of this group, Dictyostelium discoideum. The gene-dense
      chromosomes of this organism encode approximately 12,500 predicted proteins, a
      high proportion of which have long, repetitive amino acid tracts. There are many
      genes for polyketide synthases and ABC transporters, suggesting an extensive
      secondary metabolism for producing and exporting small molecules. The genome is
      rich in complex repeats, one class of which is clustered and may serve as
      centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element
      are found at the ends of each chromosome, suggesting a novel telomere structure
      and the use of a common mechanism to maintain both the rDNA and chromosomal
      termini. A proteome-based phylogeny shows that the amoebozoa diverged from the
      animal-fungal lineage after the plant-animal split, but Dictyostelium seems to
      have retained more of the diversity of the ancestral genome than have plants,
      animals or fungi.

PMID- 15875017
TI  - Topological versus chemical ordering in network glasses at intermediate and
      extended length scales.
AB  - Atomic ordering in network glasses on length scales longer than nearest-neighbour
      length scales has long been a source of controversy. Detailed experimental
      information is therefore necessary to understand both the network properties and
      the fundamentals of glass formation. Here we address the problem by investigating
      topological and chemical ordering in structurally disordered AX2 systems by
      applying the method of isotopic substitution in neutron diffraction to glassy
      ZnCl2. This system may be regarded as a prototypical ionic network forming glass,
      provided that ion polarization effects are taken into account, and has thus been
      the focus of much attention. By experiment, we show that both the topological and
      chemical ordering are described by two length scales at distances greater than
      nearest-neighbour length scales. One of these is associated with the intermediate
      range, as manifested by the appearance in the measured diffraction patterns of a
      first sharp diffraction peak at 1.09(3) A(-1); the other is associated with an
      extended range, which shows ordering in the glass out to 62(4) A. We also find
      that these general features are characteristic of glassy GeSe2, a prototypical
      covalently bonded network material. The results therefore offer structural
      insight into those length scales that determine many important aspects of
      supercooled liquid and glass phenomenology.

PMID- 15875018
TI  - Measurement of femtometre-scale atomic displacements by X-ray absorption
      spectroscopy.
AB  - The frequencies of extended X-ray absorption fine-structure (EXAFS) measurements,
      which are oscillations occurring on the high-energy side of an X-ray absorption
      edge, can be used to identify interatomic distances in materials. We have used a
      dispersive X-ray spectrometer, which has no moving components, to make rapid
      measurements with minimal energy drift of the difference in EXAFS from the Fe K
      edge in an iron-cobalt thin film undergoing periodic strain through
      magnetostriction. We show that magnetostriction can be detected by differential X
      ray absorption. The magnitude of the recorded signal relative to the noise shows
      a sensitivity to mean differential atomic motion of one femtometre: a factor of
      100 times more sensitive than that normally available.

PMID- 15875019
TI  - Slip rate variations on normal faults during glacial-interglacial changes in
      surface loads.
AB  - Geologic and palaeoseismological data document a marked increase in the slip
      rates of the Wasatch fault and three adjacent normal faults in the Basin and
      Range Province during the Late Pleistocene/Early Holocene epochs. The cause of
      this synchronous acceleration of fault slip and the subsequent clustering of
      earthquakes during the Holocene has remained enigmatic, although it has been
      suggested that the coincidence between the acceleration of slip and the shrinkage
      of Lake Bonneville after the Last Glacial Maximum may indicate a causal
      relationship. Here we use finite-element models of a discrete normal fault within
      a rheologically layered lithosphere to evaluate the relative importance of two
      competing processes that affect fault slip: postglacial unloading (the removal of
      mass), which decreases the slip rate, and lithospheric rebound, which promotes
      faster slip. We show that lithospheric rebound caused by regression of Lake
      Bonneville and deglaciation of adjacent mountain ranges provides a feasible
      mechanism for the high Holocene rates of faulting in the Wasatch region. Our
      analysis implies that climate-controlled changes in loads applied to Earth's
      surface may exert a fundamental control on the slip history of individual normal
      faults.

PMID- 15875020
TI  - A primitive therizinosauroid dinosaur from the Early Cretaceous of Utah.
AB  - Therizinosauroids are an enigmatic group of dinosaurs known mostly from the
      Cretaceous period of Asia, whose derived members are characterized by elongate
      necks, laterally expanded pelves, small, leaf-shaped teeth, edentulous rostra and
      mandibular symphyses that probably bore keratinized beaks. Although more than a
      dozen therizinosauroid taxa are known, their relationships within Dinosauria have
      remained controversial because of fragmentary remains and an unusual suite of
      characters. The recently discovered 'feathered' therizinosauroid Beipiaosaurus
      from the Early Cretaceous of China helped to clarify the theropod affinities of
      the group. However, Beipiaosaurus is also poorly represented. Here we describe a
      new, primitive therizinosauroid from an extensive paucispecific bonebed at the
      base of the Cedar Mountain Formation (Early Cretaceous) of east-central Utah.
      This new taxon represents the most complete and most basal therizinosauroid yet
      discovered. Phylogenetic analysis of coelurosaurian theropods incorporating this
      taxon places it at the base of the clade Therizinosauroiden, indicating that this
      species documents the earliest known stage in the poorly understood transition
      from carnivory to herbivory within Therizinosauroidea. The taxon provides the
      first documentation, to our knowledge, of therizinosauroids in North America
      during the Early Cretaceous.

PMID- 15875021
TI  - Discovery of the first Asian plethodontid salamander.
AB  - Nearly 70% of the 535 species of salamanders in the world are members of a single
      family, the Plethodontidae, or lungless salamanders. The centre of diversity for
      this clade is North and Middle America, where the vast majority (99%) of species
      are found. We report the discovery of the first Asian plethodontid salamander,
      from montane woodlands in southwestern Korea. The new species superficially
      resembles members of North American genera, in particular the morphologically
      conservative genus Plethodon. However, phylogenetic analysis of the nuclear
      encoded gene Rag-1 shows the new taxon to be widely divergent from Plethodon. The
      new salamander differs osteologically from putative relatives, especially with
      respect to the tongue (attached protrusible) and the derived tarsus. We place the
      species in a new genus on the basis of the morphological and molecular data. The
      distribution of the new salamander adds to the enigma of Old World plethodontids,
      which are otherwise restricted to the western Mediterranean region, suggesting a
      more extensive past distribution of the family.

PMID- 15875022
TI  - An extant cichlid fish radiation emerged in an extinct Pleistocene lake.
AB  - The haplochromine cichlid fish of the East African Great Lakes represent some of
      the fastest and most species-rich adaptive radiations known, but rivers in most
      of Africa accommodate only a few morphologically similar species of haplochromine
      cichlid fish. This has been explained by the wealth of ecological opportunity in
      large lakes compared with rivers. It is therefore surprising that the rivers of
      southern Africa harbour many, ecologically diverse haplochromines. Here we
      present genetic, morphological and biogeographical evidence suggesting that these
      riverine cichlids are products of a recent adaptive radiation in a large lake
      that dried up in the Holocene. Haplochromine species richness peaks steeply in an
      area for which geological data reveal the historical existence of Lake palaeo
      Makgadikgadi. The centre of this extinct lake is now a saltpan north of the
      Kalahari Desert, but it once hosted a rapidly evolving fish species radiation,
      comparable in morphological diversity to that in the extant African Great Lakes.
      Importantly, this lake seeded all major river systems of southern Africa with
      ecologically diverse cichlids. This discovery reveals how local evolutionary
      processes operating during a short window of ecological opportunity can have a
      major and lasting effect on biodiversity on a continental scale.

PMID- 15875023
TI  - Epistasis and balanced polymorphism influencing complex trait variation.
AB  - Complex traits such as human disease, growth rate, or crop yield are polygenic,
      or determined by the contributions from numerous genes in a quantitative manner.
      Although progress has been made in identifying major quantitative trait loci
      (QTL), experimental constraints have limited our knowledge of small-effect QTL,
      which may be responsible for a large proportion of trait variation. Here, we
      identified and dissected a one-centimorgan chromosome interval in Arabidopsis
      thaliana without regard to its effect on growth rate, and examined the signature
      of historical sequence polymorphism among Arabidopsis accessions. We found that
      the interval contained two growth rate QTL within 210 kilobases. Both QTL showed
      epistasis; that is, their phenotypic effects depended on the genetic background.
      This amount of complexity in such a small area suggests a highly polygenic
      architecture of quantitative variation, much more than previously documented. One
      QTL was limited to a single gene. The gene in question displayed a nucleotide
      signature indicative of balancing selection, and its phenotypic effects are
      reversed depending on genetic background. If this region typifies many complex
      trait loci, then non-neutral epistatic polymorphism may be an important
      contributor to genetic variation in complex traits.

PMID- 15875024
TI  - Suppression of Notch signalling by the COUP-TFII transcription factor regulates
      vein identity.
AB  - Arteries and veins are anatomically, functionally and molecularly distinct. The
      current model of arterial-venous identity proposes that binding of vascular
      endothelial growth factor to its heterodimeric receptor--Flk1 and neuropilin 1
      (NP-1; also called Nrp1)--activates the Notch signalling pathway in the
      endothelium, causing induction of ephrin B2 expression and suppression of ephrin
      receptor B4 expression to establish arterial identity. Little is known about vein
      identity except that it involves ephrin receptor B4 expression, because Notch
      signalling is not activated in veins; an unresolved question is how vein identity
      is regulated. Here, we show that COUP-TFII (also known as Nr2f2), a member of the
      orphan nuclear receptor superfamily, is specifically expressed in venous but not
      arterial endothelium. Ablation of COUP-TFII in endothelial cells enables veins to
      acquire arterial characteristics, including the expression of arterial markers NP
      1 and Notch signalling molecules, and the generation of haematopoietic cell
      clusters. Furthermore, ectopic expression of COUP-TFII in endothelial cells
      results in the fusion of veins and arteries in transgenic mouse embryos. Thus,
      COUP-TFII has a critical role in repressing Notch signalling to maintain vein
      identity, which suggests that vein identity is under genetic control and is not
      derived by a default pathway.

PMID- 15875025
TI  - LPA3-mediated lysophosphatidic acid signalling in embryo implantation and
      spacing.
AB  - Every successful pregnancy requires proper embryo implantation. Low implantation
      rate is a major problem during infertility treatments using assisted reproductive
      technologies. Here we report a newly discovered molecular influence on
      implantation through the lysophosphatidic acid (LPA) receptor LPA3 (refs 2-4).
      Targeted deletion of LPA3 in mice resulted in significantly reduced litter size,
      which could be attributed to delayed implantation and altered embryo spacing.
      These two events led to delayed embryonic development, hypertrophic placentas
      shared by multiple embryos and embryonic death. An enzyme demonstrated to
      influence implantation, cyclooxygenase 2 (COX2) (ref. 5), was downregulated in
      LPA3-deficient uteri during pre-implantation. Downregulation of COX2 led to
      reduced levels of prostaglandins E2 and I2 (PGE2 and PGI2), which are critical
      for implantation. Exogenous administration of PGE2 or carbaprostacyclin (a stable
      analogue of PGI2) into LPA3-deficient female mice rescued delayed implantation
      but did not rescue defects in embryo spacing. These data identify LPA3 receptor
      mediated signalling as having an influence on implantation, and further indicate
      linkage between LPA signalling and prostaglandin biosynthesis.

PMID- 15875026
TI  - The bipolar mitotic kinesin Eg5 moves on both microtubules that it crosslinks.
AB  - During cell division, mitotic spindles are assembled by microtubule-based motor
      proteins. The bipolar organization of spindles is essential for proper
      segregation of chromosomes, and requires plus-end-directed homotetrameric motor
      proteins of the widely conserved kinesin-5 (BimC) family. Hypotheses for bipolar
      spindle formation include the 'push-pull mitotic muscle' model, in which kinesin
      5 and opposing motor proteins act between overlapping microtubules. However, the
      precise roles of kinesin-5 during this process are unknown. Here we show that the
      vertebrate kinesin-5 Eg5 drives the sliding of microtubules depending on their
      relative orientation. We found in controlled in vitro assays that Eg5 has the
      remarkable capability of simultaneously moving at approximately 20 nm s(-1)
      towards the plus-ends of each of the two microtubules it crosslinks. For anti
      parallel microtubules, this results in relative sliding at approximately 40 nm s(
      1), comparable to spindle pole separation rates in vivo. Furthermore, we found
      that Eg5 can tether microtubule plus-ends, suggesting an additional microtubule
      binding mode for Eg5. Our results demonstrate how members of the kinesin-5 family
      are likely to function in mitosis, pushing apart interpolar microtubules as well
      as recruiting microtubules into bundles that are subsequently polarized by
      relative sliding.

PMID- 15875027
TI  - A synthetic gene-metabolic oscillator.
AB  - Autonomous oscillations found in gene expression and metabolic, cardiac and
      neuronal systems have attracted significant attention both because of their
      obvious biological roles and their intriguing dynamics. In addition, de novo
      designed oscillators have been demonstrated, using components that are not part
      of the natural oscillators. Such oscillators are useful in testing the design
      principles and in exploring potential applications not limited by natural
      cellular behaviour. To achieve transcriptional and metabolic integration
      characteristic of natural oscillators, here we designed and constructed a
      synthetic circuit in Escherichia coli K12, using glycolytic flux to generate
      oscillation through the signalling metabolite acetyl phosphate. If two metabolite
      pools are interconverted by two enzymes that are placed under the transcriptional
      control of acetyl phosphate, the system oscillates when the glycolytic rate
      exceeds a critical value. We used bifurcation analysis to identify the boundaries
      of oscillation, and verified these experimentally. This work demonstrates the
      possibility of using metabolic flux as a control factor in system-wide
      oscillation, as well as the predictability of a de novo gene-metabolic circuit
      designed using nonlinear dynamic analysis.

PMID- 15875028
TI  - Management potential.

PMID- 15875029
TI  - Making it in the biotech business.

PMID- 15875031
TI  - Nuts and bolts. Soft skills.

PMID- 15875034
TI  - Smoke signals.

PMID- 15875035
TI  - Scientists seek simple remedies to cloning conundrums.

PMID- 15875037
TI  - US policy keeps drugs out of reach in clinical trials abroad.

PMID- 15875038
TI  - Bugs gain vital ground in their battle against drugs.

PMID- 15875039
TI  - Scientists charged with choosing publication over public health.

PMID- 15875040
TI  - Sports law could even the score for women in science.

PMID- 15875041
TI  - Personalized medicine prompts push to redesign clinical trials.

PMID- 15875043
TI  - Profile: Woo-Suk Hwang.

PMID- 15875044
TI  - Strong medicine.

PMID- 15875046
TI  - HIV swiftly guts the immune system.

PMID- 15875047
TI  - Lipid let loose in pulmonary emphysema.

PMID- 15875048
TI  - Killing pain, killing neurons?

PMID- 15875049
TI  - DNA instability in the brain: survival of the 'fittest'.

PMID- 15875050
TI  - Do-all receptor takes on coagulation, inflammation.

PMID- 15875051
TI  - Radiation's outer limits.

PMID- 15875052
TI  - Muscle disease: a giant feels the strain.

PMID- 15875056
TI  - The expression of legumain, an asparaginyl endopeptidase that controls antigen
      processing, is reduced in endotoxin-tolerant monocytes.
AB  - The exposition of monocytes to lipopolysaccharide (LPS) primarily causes a
      massive inflammatory response that is then followed by a hyporesponsive state of
      these cells. This latter state is called endotoxin tolerance and is characterized
      by (i) the attenuated production of proinflammatory mediators after repeated LPS
      treatment, and (ii) the diminished antigen presentation and T-cell stimulation
      capacity. The data presented here indicate that LPS priming causes a specific
      decrease in the expression of legumain (the asparaginyl endopeptidase responsible
      for the key step in antigen processing) in monocytes. In these cells, the
      fraction of major histocompatibility complex (MHC) class II loaded with CLIP was
      increased. In contrast to monocytes, LPS priming provoked an increase of legumain
      expression in B cells. Reduced monocytic expression of legumain was also found in
      critically ill patients supporting the suitability of endotoxin tolerance as an
      experimental model of clinical postinflammatory immunodeficiency.

PMID- 15875057
TI  - Chronic periodontal disease is associated with single-nucleotide polymorphisms of
      the human TLR-4 gene.
AB  - Periodontitis is an inflammatory disease affecting the connective tissue
      surrounding the teeth leading to tooth loss. Pathogens associated with
      periodontitis interact with Toll-like receptors (TLRs) to induce cytokines
      causing and aggravating disease. We screened 197 individuals suffering from
      generalized periodontitis for the presence of Asp299Gly and Thr399Ile of TLR-4 as
      well as Arg753Gln of TLR-2 in comparison to matched controls. Single-nucleotide
      polymorphisms (SNPs) of TLR-4 were elevated among patients (odd's ratio 3.650,
      95% CI 1.573-8.467, P < or = 0.0001), while no difference was observed for TLR-2.
      TLR-4 SNPs were correlated with chronic periodontitis (odd's ratio 5.562, 95% CI
      2.199-14.04, P < or = 0.0001), but not with aggressive periodontitis. This
      observation was confirmed employing a group of periodontally healthy probands
      over 60 years of age. These data demonstrate that genetic variants of TLR-4 may
      act as risk factors for the development of generalized chronic periodontitis in
      humans.

PMID- 15875058
TI  - Differential association of the PTPN22 coding variant with autoimmune diseases in
      a Dutch population.
AB  - Protein tyrosine phosphatase PTPN22 is involved in the negative regulation of T
      cell responsiveness. Recently, the association of a coding variant of the PTPN22
      gene-R620W(1858C>T) with a number of autoimmune diseases has been described.
      Therefore, we tested the association of PTPN22 1858*T allele in Dutch early onset
      type 1 diabetes (T1D) and rheumatoid arthritis (RA) patients, as well as celiac
      disease (CD) patients, for which no previous study of PTPN22 has been reported.
      The PTPN22 variant was strongly associated with T1D in cases vs controls (P=2 x
      10(-7), OR=2.3, 95% CI=1.7-3.1) as well as in a transmission disequilibrium test
      in nuclear trio's (P=9 x 10(-9), OR=3.3, CI=2.1-5.0), RA (case/control: P=0.003,
      OR=1.8 CI =1.2-2.6), but not CD, in spite of a trend of increased homozygosity
      (P=0.05) and early age at onset (P=0.01). PTPN22 is not generally associated with
      T-cell mediated autoimmune diseases, although it might play a role in the CD
      patients with early clinical manifestation.

PMID- 15875059
TI  - Alcock's canal releasing for pudendal artery syndrome resulting from gunshot
      injury.
AB  - A 21-y-old man applied to hospital with a complaint of erectile dysfunction,
      which started soon after a gunshot injury. The entry of the bullet was at the
      middle right gluteal region without any exit hole. A pelvic X-ray revealed the
      bullet and the scattered particles. On penile Doppler ultrasonography, the peak
      systolic velocities (PCV) of the right and the left cavernosal arteries were 19
      and 29 cm/s, respectively. Pudendal angiography revealed poor visualization of
      the right pudendal artery below the level of the bullet. The patient underwent a
      right-sided Alcock's canal releasing surgery. After the operation, on control
      penile Doppler ultrasonography, PCV on the right and the left cavernosal arteries
      were 53 and 35 cm/s, respectively. The control angiography revealed a normal
      right pudendal artery. The patient was fully potent 2 y after the operation. Not
      only the entrapment of pudendal nerve but also the pudendal artery may cause
      Pudendal canal syndrome. A gunshot injury may cause such a condition due to the
      reaction caused by the bullet. Pudendal canal decompression is a simple and
      effective treatment for pudendal canal syndrome.

PMID- 15875060
TI  - Erectile dysfunction and HTLV-I infection: a silent problem.
AB  - The human T-lymphotropic virus type I (HTLV-I) is a retrovirus associated with a
      chronic myelopathy known as HTLV-I-Associated Myelopathy or Tropical Spastic
      Paraparesis (HAM/TSP). The main objective was to assess the frequency of erectile
      dysfunction (ED) in HTLV-I-infected individuals from Salvador and other cities
      from Bahia, Brazil, as well as to verify if sexual dysfunction correlates with
      urinary symptoms and overall neurological impairment. From January 2001 to April
      2004, 218 HTLV-I carriers (111 male and 107 female subjects) had complete
      clinical, neurological, and urological evaluation. They were assessed using
      standardized questionnaires to determine urinary complaints (Urinary Distress
      Inventory) and ED (Brief Male Sexual Function Inventory). Neurological impairment
      was established by Expanded Disability Status Scale (EDSS) from 0 to 10. HAM/TSP
      was considered as EDSS> or =2. A total of 17 males had clinically defined HAM/TSP
      (group 1). From the 94 HTLV-I-infected males, 62 were selected (group 2) and
      paired by age with patients in group 1. A total of 79 individuals were selected
      for this study. The age ranged from 35 to 81 y (mean=47.9+/-9.65). The percentage
      of ED in the studied population was 40.5%. In the HAM/TSP group, ED frequency was
      88.2%. The associations among sexual dissatisfaction, erectile dysfunction,
      urinary symptoms (frequency, nocturia, and urgency) and EDSS> or =2 were
      statistically significant. In HAM/TSP, there is a slow and progressive
      degeneration of the lateral funiculus of the spinal cord. HTLV-I-infected
      individuals present a high frequency of ED and it is closely associated to
      urinary symptoms and the overall neurological picture. The HTLV-I carriers
      already had prominent compromise of the sexual activity.

PMID- 15875061
TI  - The Sexual Health Inventory for Men (SHIM): a 5-year review of research and
      clinical experience.
AB  - The Sexual Health Inventory for Men (SHIM) is a widely used scale for screening
      and diagnosis of erectile dysfunction (ED) and severity of ED in clinical
      practice and research. In reviewing the SHIM-related literature, we sought to
      provide a compendium of studies in which the SHIM was used, to provide a
      systematic framework for organizing and evaluating the studies, and to provide a
      status report on the SHIM and its impact on the management of male sexual
      dysfunction. Using a Medline search, we found that the SHIM was an integral
      measure in at least 21 studies on the prevalence of ED, 23 studies on the
      efficacy of ED interventions, and eight other (mainly correlational) studies. The
      quantity of research and quality of scholarship on the SHIM provide testimony to
      its positive impact on understanding and improving male sexual function. These
      scientific contributions are likely to remain influential in coming years.

PMID- 15875062
TI  - Endobronchial mimics of primary endobronchial carcinoma: a clinical study of 25
      cases.
AB  - While endobronchial lesions that present with symptoms of obstruction may be
      reflective of primary bronchogenic malignancy, there have been a number of
      reports of bronchial lesions other than primary bronchogenic carcinoma simulating
      primary endobronchial epithelial malignancy clinically. Twenty-five cases of
      symptomatic endobronchial disease were encountered with pathological assessment
      demonstrating an endobronchial process other than carcinoma, representing
      metastatic disease (breast, colon, renal, head and neck origin), fungal
      infection, Hodgkin's lymphoma, primary bronchogenic melanoma, lipoma, broncholith
      and inflammatory pseudopolyp. The present report underscores the potential
      pathogenetic heterogeneity encountered in lesions presenting with signs and
      symptoms of endobronchial obstruction, emphasizing the critical role of biopsy
      for establishing a definitive diagnosis.

PMID- 15875063
TI  - The use of noninvasive mechanical ventilation for the treatment of acute
      exacerbations of chronic obstructive pulmonary disease in Canada.
AB  - BACKGROUND: Noninvasive mechanical ventilation (NIMV) is accepted as a life
      saving treatment for patients presenting to the emergency department and other
      acute care settings with severe exacerbations of chronic obstructive pulmonary
      disease (COPD). OBJECTIVES: It was hypothesized that there is marked national
      variability in the use of NIMV. Therefore, the use of NIMV for COPD exacerbations
      in urban centres across Canada was evaluated. METHODS: All Canadian hospitals
      affiliated with a university training program were surveyed, and a request for
      involvement in this survey was posted on the Canadian Society of Respiratory
      Therapy professional practice listserv. Survey information was received from all
      33 sites (100%) that were contacted. RESULTS: Marked differences in the
      application of NIMV were identified across all regions in Canada, ranging from
      requiring extensive monitoring in the intensive care unit to application on a
      general internal medical unit with intermittent noninvasive blood pressure
      monitoring. There were sites that rarely used NIMV for COPD exacerbations and
      others where it was routine practice. CONCLUSIONS: NIMV is a life-saving
      treatment for acute exacerbations of COPD. Despite clear clinical evidence, its
      use has not penetrated throughout all the larger urban hospitals in Canada. This
      may be more problematic in sites without 24 h respiratory therapy support. There
      are barriers to the routine application of NIMV that can be overcome using
      established guidelines and available evidence.

PMID- 15875064
TI  - The lack of association between bacille Calmette-Guerin vaccination and
      clustering of Aboriginals with tuberculosis in western Canada.
AB  - BACKGROUND: Tuberculosis (TB) remains a major health problem for Aboriginal
      people in Canada, with high rates of clustering of active TB cases. Bacille
      Calmette-Guerin (BCG) vaccination has been used as a preventive measure against
      TB in this high-risk population. OBJECTIVES: The study was designed to determine
      if BCG vaccination in Aboriginal people influenced recent TB transmission through
      an analysis of the clustering of TB cases. METHODS: A retrospective analysis of
      all culture-positive Mycobacterium tuberculosis cases in Aboriginal people in
      western Canada (1995 to 1997) was performed. Isolates were analyzed using
      standard methodology for restriction fragment length polymorphism and
      spoligotyping. RESULTS: Of 256 culture-positive Aboriginal TB cases, BCG status
      was confirmed in 216 (84%) cases; 34% had been vaccinated with BCG, 57% were male
      and 56% were living on-reserve. Patients who had been vaccinated with BCG were
      younger than unvaccinated individuals (mean age 32.4+/-1.65 years versus 45.0+/
      1.8 years, P<0.0001). Clustering was found in 62% of cases: 59% of non-BCG
      vaccinated cases were clustered versus 68% of those vaccinated with BCG (P=0.16).
      Younger patients (younger than 60 years of age) were more likely to be clustered
      in the univariate analysis (P<0.01). When age, sex, province, and HIV and reserve
      status were controlled for, BCG vaccination was not associated with clustering
      (OR 1.3, 95% CI 0.7 to 2.6). CONCLUSIONS: BCG vaccinated Aboriginal people were
      no less likely to have active TB from recently transmitted disease. BCG
      vaccination appears to have limited value in preventing clustering of TB cases
      within this high-risk community.

PMID- 15875065
TI  - Epidemiology of community-acquired pneumonia in Edmonton, Alberta: an emergency
      department-based study.
AB  - Patients aged 17 years and older who presented to seven emergency departments in
      Edmonton, Alberta over a two-year period with community-acquired pneumonia
      (n=8144) were studied. The admission rates were 271/100,00 and 296/100,000
      persons for year 1 and year 2 of the study, respectively. The admission rate
      increased with increasing age, peaking at 4639/100,000/year for those 90 years of
      age and older. In contrast, the percentage of patients who were admitted to an
      intensive care unit was highest for those in the younger age groups between 17
      and 59 years of age. From 59 years of age and older, there was a progressive
      decline in the percentage of patients admitted to an intensive care unit, with
      approximately 1% of those in the 90 years and older age group admitted. A
      pronounced seasonal effect on the number of patients presenting to emergency
      department was also noted. During the winter months, there was up to a 50%
      increase in the number of cases compared with the summer months.

PMID- 15875066
TI  - Increased expression of the calcium-activated chloride channel hCLCA1 in airways
      of patients with obstructive chronic bronchitis.
AB  - BACKGROUND: Interleukin (IL)-9 and its effect on enhancing the human calcium
      activated chloride channel 1 (hCLCA1) expression have been shown to induce mucin
      production. Increased expression of hCLCA1 may, in turn, contribute to mucus
      overproduction in chronic obstructive pulmonary disease (COPD) with a chronic
      bronchitis (CB) phenotype. OBJECTIVE: To determine the expression of IL-9, IL-9
      receptor (IL-9R), hCLCA1 and mucoglycoconjugates in COPD. METHODS: Bronchial
      biopsies were obtained from six patients with obstructive CB and six healthy
      control subjects. IL-9, IL-9R and hCLCA1 expression were detected using
      immunohistochemistry. Additionally, in situ hybridization was performed to
      determine the expression of hCLCA1 messenger RNA. Mucin production was assessed
      using periodic acid-Schiff staining. RESULTS: There was a significantly higher
      number of IL-9 immunoreactive cells in the submucosa of patients with COPD than
      that of healthy control subjects (P<0.05). Also, a significant increase in the
      expression of IL-9R, hCLCA1 (protein and messenger RNA) and mucin (periodic acid
      Schiff-positive cells) was noted in the bronchial epithelium of patients with
      COPD compared the control subjects (P<0.05). CONCLUSION: Increased expression of
      IL-9, IL-9R and hCLCA1 in the bronchial mucosa of patients with obstructive CB
      suggests that mucus overproduction in this disease may be, at least in part, due
      to hCLCA1.

PMID- 15875067
TI  - Update on the British Columbia Thoracic Society's Annual Case Challenge.

PMID- 15875068
TI  - Jumping to conclusions: things are never what they seem.
AB  - A 46-year-old Aboriginal man presented with a massive pleural effusion. A
      diagnosis of sarcoidosis was established. To the author's knowledge, this is the
      first reported case of sarcoidosis in a North American Aboriginal patient.

PMID- 15875069
TI  - A case of congenital cutis laxa (generalized elastolysis).
AB  - Cutis laxa (generalized elastolysis) is characterized by sagging folds of loose
      skin on the face and trunk. Although grouped with hyperelastic skin conditions
      such as Ehlers-Danlos syndrome, cutis laxa shows an almost total lack of skin
      elasticity. Because it is a generalized state, it may present as an abnormality
      in the connective tissue of more than one organ system. The authors report a
      patient who had end-stage renal failure related to heavy chain disease, a
      recognized association of cutis laxa. Although the patient's vascular
      abnormalities were significant, she died of respiratory failure at 41 years of
      age from cutis laxa-induced emphysema.

PMID- 15875070
TI  - Systemic actinomycosis mimicking pelvic malignancy with pulmonary metastases.
AB  - A 40-year-old woman presented with profound weight loss, anemia and multiple
      pulmonary nodules. Further investigation revealed a hepatic abscess and a pelvic
      mass associated with an intrauterine device. Cultures of the hepatic abscess and
      from peripheral blood demonstrated Actinomyces species. The patient underwent an
      exploratory laparotomy and hysterectomy. Pathological examination showed
      characteristic sulphur granules of actinomycosis. Long-term therapy with high
      dose intravenous penicillin resulted in clinical and radiographic improvement.

PMID- 15875071
TI  - Direct measurement of the singlet oxygen lifetime in zeolites by near-IR
      phosphorescence.
AB  - Time-resolved near-IR phosphorescence spectroscopy was employed to determine the
      lifetime of singlet oxygen in Y-zeolites and porous silica and it was found to
      depend strongly on the alumina content of the zeolite.

PMID- 15875072
TI  - Hydrogen peroxide evolution during V-UV photolysis of water.
AB  - Hydrogen peroxide evolution during the vacuum-ultraviolet (V-UV, 172 nm)
      photolysis of water is considerably affected by the presence of oxalic acid
      (employed as a model water pollutant) and striking differences are observed in
      the absence and in the presence of dioxygen.

PMID- 15875073
TI  - PROPHIS: parabolic trough-facility for organic photochemical syntheses in
      sunlight.
AB  - The PROPHIS facility is an efficient tool for the synthesis of chemicals with
      moderately concentrated sunlight on a semi-technical scale. The feasibility of
      selected solar photochemical reaction classes--including heterogeneous and
      homogeneous reactions--has been demonstrated using various set-ups of the plant.
      This paper outlines the potential of solar photochemistry by representative
      examples.

PMID- 15875074
TI  - Fate of flavins in sensitized photodegradation of isohumulones and reduced
      derivatives: studies on formation of radicals via EPR combined with detailed
      product analyses.
AB  - Photodegradation of isohumulones accounts for formation of the lightstruck flavor
      in beer. The reactions involved are mediated by riboflavin, a natural
      photosensitizer present in beer in ppb quantities. The results of an
      investigation of this sensitized degradation process are presented herein.
      Product analyses and electron paramagnetic resonance spectroscopy, in steady
      state as well as in time-resolved mode, offer extensive insight into the
      photophysical and photochemical details of the degradation mechanism. In contrast
      to energy transfer and Norrish type I alpha-cleavage reactions that take place on
      direct irradiation of isohumulones, the sensitization pathway proceeds via one
      electron redox chemistry involving the excited triplet state of riboflavin and
      derivatives. The flavin semiquinone radical thus formed could be readily
      detected, either by steady state or by time-resolved electron paramagnetic
      resonance spectroscopy. Superimposed signals in the spectra revealed the presence
      of radical fragments derived from isohumulones or tetrahydroisohumulones, which,
      on recombination with riboflavin semiquinone radicals, produced stable reaction
      products that were identified by HPLC-MS. However, no superimposed signals were
      observed on sensitized irradiation of dihydroisohumulones.

PMID- 15875075
TI  - Contrasting action of flavonoids on phototoxic effects induced in human skin
      fibroblasts by UVA alone or UVA plus cyamemazine, a phototoxic neuroleptic.
AB  - The potential protective effects of the flavanol catechin, the flavonol
      quercetin, the flavones, luteolin and rutin, and the isoflavones, genistein and
      daidzein, against the photo-oxidative stress induced by ultraviolet A radiation
      (UVA) and by phototoxic reactions resulting from the interaction of UVA with
      drugs and chemicals, has been assessed with cultured human skin fibroblasts.
      Lipid peroxidation and cell death have been chosen as model photobiological
      damage induced by UVA alone or photosensitized by cyamemazine (CMZ) and its
      photoproduct possessing phototoxic properties. Contrasting effects of flavonoids
      are observed. The flavanol, the flavonol and the flavones may protect against
      lipid peroxidation and cell death induced by 30 J cm(-2) of UVA alone or CMZ plus
      10 J cm(-2) UVA. On the other hand, an amplification of the photodamage may be
      observed with isoflavones. A concentration-dependence study demonstrates that
      among the protective flavonoids, quercetin is the most efficient. The very
      effective protection brought by quercetin may result from its ability to scavenge
      reactive oxygen species produced by the photo-oxidative stress. However, the
      modification of membrane properties and the alteration of the lysosomal function
      by quercetin may not be neglected in these protective effects. The amplification
      of the photodamage by isoflavones is in sharp contrast with previous literature
      data demonstrating photoprotection by genistein. As a consequence, it may be
      concluded that an eventual antioxidant action of genistein may strongly depend on
      cells and photosensitizers. Furthermore such contrasting pro-versus anti-oxidant
      effects have to be taken into account when using flavonoid mixtures of plant
      extracts.

PMID- 15875076
TI  - Enhanced UV exposure on a ski-field compared with exposures at sea level.
AB  - Personal erythemal UV monitoring badges, which were developed to monitor the UV
      exposure of school children, were used to measure UV exposures received by one of
      the authors (MA) at the Mt Hutt ski-field, in New Zealand. These were then
      compared with measurements taken at the same times from a nearby sea level site
      in Christchurch city. The badges were designed to give instantaneous readings of
      erythemally-weighted (i.e., "sun burning") UV radiation and were cross-calibrated
      against meteorological grade UV instruments maintained by the National Institute
      of Water & Atmospheric Research (NIWA). All skiing and calibration days were
      clear and almost exclusively cloud free. It was found that the UV maxima for
      horizontal surfaces at the ski-field (altitude approximately 2 km) were 20-30%
      greater than at the low altitude site. Larger differences between the sites were
      observed when the sensor was oriented perpendicular to the sun. The personal
      doses of UV received by a sensor on the skier's lapel during two days of skiing
      activity were less than those received by a stationary detector on a horizontal
      surface near sea level. The exposures depended strongly on the time of year, and
      in mid-October the maximum UV intensity on the ski-field was 60% greater than in
      mid-September. The UV exposure levels experienced during skiing were smaller than
      the summer maxima at low altitudes.

PMID- 15875077
TI  - Fluorescence image-guided brain tumour resection with adjuvant metronomic
      photodynamic therapy: pre-clinical model and technology development.
AB  - Fluorescence-guided resection (FGR) and photodynamic therapy (PDT) have
      previously been investigated separately with the objectives, respectively, of
      increasing the extent of brain tumour resection and of selectively destroying
      residual tumour post-resection. Both techniques have demonstrated trends towards
      improved survival, pre-clinically and clinically. We hypothesize that combining
      these techniques will further delay tumour re-growth. In order to demonstrate
      technical feasibility, we here evaluate fluorescence imaging and PDT treatment
      techniques in a specific intracranial tumour model. The model was the VX2
      carcinoma grown by injection of tumour cells into the normal rabbit brain. An
      operating microscope was used for white light imaging and a custom-built
      fluorescence imaging system with co-axial excitation and detection was used for
      FGR. PDT treatment light was applied by intracranially-implanted light emitting
      diodes (LED). The fluorescent photosensitizer used for both FGR and PDT was ALA
      induced PpIX. For PDT, ALA (100 mg kg(-1)) and low light doses (15 and 30 J) were
      administered over extended periods, which we refer to as metronomic PDT (mPDT).
      Eighteen tumour bearing rabbits were divided equally into three groups: controls
      (no resection); FGR; and FGR followed by mPDT. Histological whole brain sections
      (H&E stain) showed primary and recurrent tumours. No bacteriological infections
      were found by Gram staining. Selective tumour cell death through mPDT-induced
      apoptosis was demonstrated by TUNEL stain. These results demonstrate that the
      combined treatment is technically feasible and this model is a candidate to
      evaluate it. Further optimization of mPDT treatment parameters (drug/light dose
      rates) is required to improve survival.

PMID- 15875078
TI  - Inhibitors of proteases as anticancer drugs.
AB  - Proteolytic processes are necessary for normal physiological functions in the
      body. Failure in the biological control mechanisms of proteolytic activities may
      cause various diseases, for example, it may enable tumor invasion and metastasis.
      In the metastatic process, proteolytic enzymes play an important role in
      mediating passage of the malignant cell through the cell membrane. Tumor cell
      migration and invasion into the surrounding extracellular matrix is facilitated
      by a variety of cell surface-associated proteolytic enzymes: matrix
      metalloproteinases (MMPs), cysteine proteases including cathepsins B and L,
      aspartic protease cathepsin D, and serine proteases including plasmin and
      urokinase plasminogen activator (uPA). Many of the natural and synthetic
      inhibitors of the proteases prevent the dissemination of cancer cells and have
      also inhibitory effect on tumor growth. Thus inhibition of protease activity by
      low molecular weight inhibitors represents a promising strategy for anticancer
      and antimetastatic therapy. The review surveys low molecular inhibitors of MMPs,
      uPA and lysosomal proteases.

PMID- 15875079
TI  - Estimation of taxol influence on changes in tubulin and vimentin systems in K-562
      and HL-60 cell lines by immunofluorescence microscopy.
AB  - The cytoskeletal system may be considered as an additional pathway involved in
      process of apoptosis and can be promising target for development of new
      chemotherapies. The study describes alterations in the distribution of vimentin
      and tubulin in taxol treated K-562 and HL-60 cells in relation to apoptotic
      changes. K-562 and HL-60 cells were treated with taxol in a range of
      concentrations (0.02-10 microM) for 72 hours. Significant changes in distribution
      of studied proteins occurred in the range 2-10 microM of taxol. K-562 cells
      showed thin network of vimentin distributed throughout cells or collapsed on
      nucleus. There were also cells with bright aggregates remembering apoptotic
      bodies. HL-60 cells showed strong labeling of vimentin in the cytoplasm as well
      as at the site of apoptotic bodies. Vimentin collapsed on the nucleus, labeling
      at poles and along the major axis of the cell were also seen. K-562 and HL- 60
      cells showed radial labeling of tubulin from the centre, aggregates at the
      surface and bundled microtubules. These findings indicate that alterations in
      expression of studied cytoskeletal proteins after treatment with taxol were dose
      dependent and related with characteristic features of apoptosis.

PMID- 15875080
TI  - Prognostic significance of mitotic and apoptotic index and the DNA cytometry in
      head and neck cancer.
AB  - The lack of suitable criteria to predict the response to chemo- and or
      radiotherapy for individual patients with squamous cell carcinoma of the head and
      neck (HNSCC) remains still a major problem. This study was conducted to analyze
      prognostic significance of mitotic and apoptotic index and the DNA flow
      cytometric analysis of HNSCC to the recurrence-free survival time and to the
      overall survival. The analysis was carried out in a set of 56 patients suffering
      from carcinoma of the pharynx and supraglottis. Most patients (96.7%) underwent
      neoadjuvant chemotherapy, followed by surgery and postoperative irradiation.
      Besides routine examinations, flow cytometric analysis was performed, as well as
      p53 and Ki-67 markers and mitotic and apoptotic index were established by means
      of immunohistochemistry. Event-free survival (EFS) and overall survival (OS) were
      accepted as primary endpoints for the prognostic analyses. All the examined
      potential markers entered standard Kaplan-Meier survival analysis and Cox
      regression modeling. Statistical significance of prognostic factors was first
      examined in univariate models and all the parameters subsequently entered
      multivariate models. The analyses revealed significant prognostic position of
      advanced clinical stage (III+IV) and increased proliferative activity as primary
      risk factors (p<0.01) that typically positively correlate with increased mitotic
      activity and G2/M cell fraction. Better survival results obtained for grade 3-4
      as compared to grade 1-2 were caused by molecular parameters that make these
      samples similar to less risk cases. Cytokinetic parameters and proliferation
      activity were found as important predictors of the second level (after
      recognizing stage, grade and DNA status of the tumor). Multivariate combination
      of these markers contributed namely to the prognosis of early risk event: a ratio
      S phase cell fraction/G2M cell fraction was found to be the key prognostic factor
      (p<0.01). Early risk events are associated with increased mitotic activity,
      decreased apoptic rate, decreased S phase cell fraction and significantly
      increased G2/M fraction.

PMID- 15875081
TI  - Comparative analysis of thymidylate synthase, thymidine phosphorylase and
      dihydropyrimidine dehydrogenase expression in colorectal cancer and surrounding
      normal tissue.
AB  - Thymidylate synthase [TS], thymidine phosphorylase [TP] and dihydropyrimidine
      dehydrogenase [DPD] play the essential role in the activation and catabolism of
      the fluoropyrimidines used in cancer therapy. Its expression may influence the
      antitumor activity or toxicity of these drugs. We studied the expression levels
      of selected enzymes in colorectal tumors and adjacent normal mucosa. The analysis
      of TS, TP and DPD gene expression was performed using quantitative Real time PCR
      technique (Roche) in 15 (TS), 64 (TP) and 12 (DPD) of 64 colorectal cancer
      patients. The mean gene expression of TS, TP and DPD was found to be 3.29; 3.79
      and 8.24 in tumors and 1.88; 3.80 and 19.69 in normal mucosa. The corresponding
      median gene expression was 1.87; 2.32 and 4.50 for tumors and 2.14; 2.63 and
      11.64 for normal tissue. We did not find any significant differences in TS, TP
      and DPD gene expression between colorectal tumor and surrounding mucosa.

PMID- 15875082
TI  - Myeloid enzymes profile related to the immunophenotypic characteristics of blast
      cells from patients with acute myeloid leukemia (AML) at diagnosis.
AB  - The purpose of this study was to assess the possible relationship between the
      cytochemical enzyme profile and immunophenotypic characteristics of distinct
      acute myeloid leukemia (AML) subtypes in discrete stages of leukemic cells
      maturation. As the proportion of leukemic blast cells is critical for exact
      cytochemical analysis, study was restricted to the evaluation of 48 adult and
      pediatric patients with newly diagnosed AMLs with 80% or more blasts in analyzed
      samples. The cytochemical investigation of myeloperoxidase (MPO), Sudan black B
      (SBB), chloroacetate esterase (CAE), alpha-naphthyl butyrate esterase (ANBE),
      alpha-naphthyl acetate esterase (ANAE) and acid phosphatase (AP) in peripheral
      blood and/or bone marrow was performed. The immunophenotype was examined for the
      maturation dependent myeloid antigens CD13, CD33, CD11b, CD14, CD15, CD65, CD36,
      cytoplasmic MPO, non-lineage associated CD34 and HLA-DR antigens, lymphoid-
      associated antigens CD7, CD4, CD38 as well as natural killer cell associated
      marker CD56. Flow cytometry by double marker staining and visualization of
      pathologic cells in dot plots reflected immunophenotypic aberrancy and degree of
      cell maturation. The patients were classified into AML subtypes M0- M2, M3, M4
      and M5 according to the main morphological, cytochemical and immunophenotypical
      features. The variable combinations of MPO, SBB, CAE and ANBE were identified in
      relation to immunophenotype. The cytochemical profile of blasts was in
      concordance with immunophenotype, particularly in more differentiated AML
      subtypes, M3, M4 and M5. The findings of myeloid antigens expression and
      cytochemical features in poorly differentiated AML subtypes showed no practical
      relevance of cytochemical analysis. Notwithstanding that the cytochemical
      analysis of AML subtypes not sufficiently identifies the distinct aberrancies in
      heterogeneous leukemic blast cell populations, evaluation of the cytochemical
      profile in connection with immunophenotyping may help to classify the AML
      patients to relevant subtypes with more accuracy.

PMID- 15875083
TI  - Modulation of BCRP mediated atypical multidrug resistance phenotype by RNA
      interference.
AB  - Multidrug resistance (MDR) in human cancers is one of the major causes of failure
      of chemotherapy. The emergence of breast cancer resistance protein (BCRP), a
      member of the ABC transporter family, has necessitated the development of
      antagonists. To overcome the BCRP-mediated atypical multidrug drug resistance,
      two small interfering RNA constructs (RNAi) targeting two different regions of
      BCRP mRNA were designed to inhibit the atypical MDR expression by transfecting
      them into MCF-7/MX100 cell lines. The multidrug resistance index to mitoxantrone
      and the intensity of mitoxantrone fluorescence of MCF-7/MX100 decreased after
      transfected by pSUPER-BCRP-A and pSUPER-BCRP-B respectively; the BCRP mRNA level
      and the BCRP protein level of MCF-7/MX100 decreased after treated with pSUPER
      BCRPs. The two constructed RNAi plasmids could reverse the atypical mutidrug
      resistance mediated by BCRP, but neither can reversed it completely, this may be
      due to low transfection efficiency and transient transfection.

PMID- 15875084
TI  - Oridonin-induced apoptosis in leukemia K562 cells and its mechanism.
AB  - Oridonin, an extract from the Chinese herb Rabdosia rubescens, is currently one
      of the most important traditional Chinese herbal medicines. Recently oridonin has
      been reported to have anti- tumor effects in a large variety of malignant
      diseases. In this study, we investigated the apoptotic inducing effect of
      oridonin in leukemia K562 cells and its mechanism. Cell growth inhibition was
      measured using a microculture tetrazolium assay, apoptosis was measured by flow
      cytometry and electron microscopy as well as by DNA fragmentation analysis.
      Telomerase activity was measured by TRAP-enzyme- linked immunosorbent assay, and
      the expression of Bcl-2 and Bax proteins was detected by western blot analysis.
      The results showed that oridonin could inhibit the proliferation and induce
      apoptosis on leukemia K562 cells remarkably. Telomerase activity as well as Bcl-2
      expression was down- regulated, while Bax expression was up-regulated
      concurrently, when apoptosis ocurred. We therefore conclude that oridonin
      demonstrated anti-proliferative and apoptosis-inducing effects on K562 cells in
      vitro, and that changes in bcl-2 and bax protein levels as well as telomerase
      activity may play an important role in its mechanism of action.

PMID- 15875085
TI  - EGFR LI and Ki-67 LI are independent prognostic parameters influencing survivals
      of surgically treated squamous cell lung cancer patients.
AB  - In literature there are still opinion differences concerning the prognostic
      significance of epidermal growth factor receptor (EGFR) expression and
      proliferative potential in patients with non small cell lung cancer (NSCLC). This
      prompted us to study those parameters. The Ki-67 labeling index (Ki-67 LI), EGFR
      labeling index (EGFR LI), and mitotic index (MI) were analyzed in the group of 78
      consecutive, surgically treated squamous cell lung cancer (SqCLC) patients. The
      expression of Ki-67 and EGFR protein was visualized on formalin fixed, paraffin
      embedded sections using immunohistochemistry (IHC). Mitotic index was assessed on
      formalin fixed, paraffin embedded sections, stained with hematoxylin and eosin
      using morphological criteria. Mean values of Ki-67 LI and MI were higher for
      G2+G3 tumors than for G1 tumors. EGFR LI was higher for G1+G2 than for G3 tumors,
      and for pT3 than for pT1+pT2 tumors. Patients having tumors with Ki-67 < or =28%
      or (EGFR LI < or =13% or EGFR LI >80%) survived significantly shorter than those
      having tumors with Ki-67 LI >28% or 13%< EGFR LI < or =80%. In multivariate
      analysis, 13%> or = EGFR LI <80% and Ki-67 LI < or =28% were independent negative
      prognostic parameters influencing survivals of SqCLC patients.

PMID- 15875086
TI  - Allogeneic non-myeloablative hematopoietic stem cell transplantation for
      treatment of metastatic renal cell carcinoma -- single center experience.
AB  - We evaluated the efficacy of allogeneic non-myeloablative stem cell
      transplantation (NST) in patients with metastatic renal cell carcinoma (RCC). A
      total of 5 patients received blood stem cells from HLA identical siblings.
      Conditioning consisted of: cyclophosphamide 60 mg/kg/d, days -7 to -6 and
      fludarabine 25 mg/m2/d for consecutive days [days -5, -4, -3, -2, -1]. The median
      CD34+ cell dose was 3.34 million/kg. Immunosuppression consisted of cyclosporine
      A and methotrexate. Among all, four patients achieved full donor chimerism with a
      median of 89 days. One patient rejected the graft and received the second
      transplantation. Grade II-III acute GVHD occured in 3 patients. None of patients
      achieved complete or partial response and there were only two mixed responses.
      All patients died due to cancer progression. There were no transplant-related
      deaths. Summarising, NST regimen allows allogeneic engraftment with low treatment
      related mortality in this high-risk population of patients. Acute and chronic
      GVHD are the major morbidities. Progression is common after NST in unselected
      patients with advanced RCC. However, regression of some metastases suggests that
      the graft versus tumor effect may occur after this type of treatment. At present
      such a procedure should be considered as an experimental approach.

PMID- 15875087
TI  - Gemcitabine plus cisplatine and paclitaxel (GCP) in second-line treatment of germ
      cell tumors (GCT): a phase II study.
AB  - The aim of the study was to determine the efficacy and toxicity of gemcitabine,
      cisplatin and paclitaxel (GCP) combination as a first salvage treatment of
      patients with relapsed GCT. Four courses of paclitaxel 175 mg/m(2) and cisplatin
      50 mg/m(2), both on day 1, and gemcitabine 1000 mg/m(2), on days 1 and 8, every 3
      weeks, were given to 12 consecutive patients who had failed standard 1st line
      treatment. Six patients (50%; 95% CI 21-79%) achieved favourable response and two
      of them are maintained 38+ and 29+ months. Median survival time was 16 months
      (range, 0.77-38+). All, but two patients had hematological toxicity Gr3-4 with
      infectious complication seen only in 6 courses of therapy. GCP is an active
      second-line combination regimen for relapsed GCTs with acceptable toxicity
      profile. However the results of this study did not show expected treatment
      efficacy and we raise the idea of cisplatin dosage relevance in this combination.

PMID- 15875088
TI  - Blood and tissue selenium concentrations and glutathione peroxidase activities in
      patients with prostate cancer and benign prostate hyperplasia.
AB  - Prostate cancer (PC) is the most common cancer in men and a leading cause of
      cancer death. Prostatic gland accumulates reasonably high amount of selenium
      (Se), the element that prevents the development of PC. It is hypothesized that
      some selenoproteins inhibit the transformation of normal prostate epithelium into
      neoplasm. We studied Se levels in whole blood, plasma and prostate of 32 PC and
      40 benign prostate hyperplasia (BPH) patients and in the control group composed
      of 39 healthy subjects. The selenoenzyme glutathione peroxidase (GSH-Px) was also
      measured in the patients' red cells, plasma and prostate tissue. Se concentration
      in whole blood and plasma in both groups of patients was lower as compared with
      controls, while in prostate gland it was significantly higher in PC than in BPH
      patients and controls. Red cell GSH-Px activity was the same in PC patients and
      controls but significantly lower in BPH patients. Plasma GSH-Px activity was
      significantly lower in PC patients than in the control group, and prostate GSH-Px
      activity was significantly lower in PC patients as compared with BPH patients.
      Since Se has anticancer properties, it is very likely that its low level in blood
      may facilitate the development of cancer. A higher level of Se in prostate of PC
      patients has no influence on GSH-Px activity in the gland.

PMID- 15875089
TI  - Low mutational rate of K-ras codon 12 in singular bronchoscopy specimens in
      suspected lung cancer.
AB  - Mutations of the K-ras gene are found in a subset of non-small- cell lung
      carcinomas (NSCLC). The aim of our study was to determine the K-ras codon 12
      mutation in the first, singular bronchoscopy specimen in parallel with the
      cytological examination for the diagnosis of lung cancer. Samples were obtained
      by diagnostic bronchoscopy in 140 patients with suspected lung tumors. The
      analysis of K-ras mutations was carried out by a sensitive two-step mutation-
      enriched polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) assay. This method has been confirmed earlier to be positive for mutated
      tumor cells and negative for normal lung parenchyma and bronchus. Of the 140
      patients with suspected cancer, 93 were diagnosed as NSCLC by cytology or
      histology in either the same specimen used for the detection of K-ras mutation or
      in later biopsies. However, only four K-ras codon 12 mutations were detected in
      the first bronchoscopic material: one in adenocarcinoma, two in squamous cell
      tumors, and one mutation was found in a patient with dysplasia which was
      diagnosed later as a squamous cell carcinoma. Our findings indicate that although
      the K-ras (codon 12) mutation is a gene lesion infrequently detectable in a
      singular specimen taken at the first bronchoscopy examination in cases of
      clinically suspected lung cancer, the detection of this mutation can help to
      confirm the cytological diagnosis of NSCLC or may be even diagnostic in
      cytologically negative cases.

PMID- 15875090
TI  - Effect of testosterone on growth of P388 leukemia cell line in vivo and in vitro.
      Distribution of peripheral blood T lymphocytes and cell cycle progression.
AB  - In transplanted mice, the P388 tumor grew better in castrated than in non
      castrated (NC) mice. The proportion of CD8+ in the blood was more numerous in NC
      mice. The T cell subsets (CD4+ and CD8+) were also high in the mice with small
      tumor tissue (<10 mg). The correlation observed between the tumor weight and T
      cell subset in PBL and in the mice with small tumors could confirm the important
      intervention of CD4+ and CD8+ cells to inhibit growth of tumor. Depo-testosterone
      (DT) injection reduced strongly weight and tumor growth in mice. On top of that,
      DT administration induced a significant increase in the percentage of blood CD8+
      cells in grafted mice. The effect of DT was studied on the cell cycle
      progression, in tumor tissue of P388 tumor bearing BDF1 mice and in P388 murine
      leukemia cell line in culture. The cell cycle analysis in tumor tissue showed
      that DT decreased both the cells in S phase and the proliferating leukemic cells,
      with accumulation of cells in G0/G1 phase. The testosterone can inhibit the
      proliferation of leukemic cells with a pharmacological dose (10(-7) M). This
      growth inhibition, dose and time dependent, was associated with cell cycle
      arrest; P388 cells accumulates in G0/G1 phase. We also observed a correlation
      between tumor weight and the percentage of cells in G0/G1 and the relative number
      of cells in proliferative state (S + G2/M). To conclude, our experiments reported
      that testosterone prevents the growth of tumor: indirectly by modulation of
      subsets T cells distribution and directly by the alteration of the cell cycle.

PMID- 15875091
TI  - Primary lymphoma of the liver -- morphological and clinical analysis of 6 cases.
      Success of aggressive treatment.
AB  - Histological, clinical and immunohistochemical analysis of 6 cases of primary
      liver lymphomas (PLL) are presented. PLL represents 4.3% of primary malignant
      liver tumors diagnosed in our department. The patients were relatively young
      people, who despite the presence of a large tumor, were in good general health
      status. There were no signs of scirrhosis, and cancer markers were normal. All
      lymphomas were CD20, CD79a, BAX positive, CD3, CD30, EMA, CD10, CD5, CD59, c-myc,
      Bcl2, EBV(LMP), CK negative. The proliferation index (Ki67) was high, ranging
      from 50-100%. In two cases positive staining for Bcl6 and in another one for
      cyclin D1 was obtained. The major histological type of the tumor was diffuse
      large B-cell lymphoma. Positive immunohistochemical results with BAX and the lack
      of Bcl2, c-myc and CD59 are associated with better prognosis. We have not
      confirmed the value of Bcl6 and CD10 stains as a predictor of poor outcome.
      Despite clinically advanced stage at the time of diagnosis, if treated
      appropriately, the primary lymphoma of the liver has relatively good prognosis
      (five of our patients are alive).

PMID- 15875092
TI  - Foams in contact with solid boundaries: equilibrium conditions and conformal
      invariance.
AB  - A liquid foam in contact with a solid surface forms a two-dimensional foam on the
      surface. We derive the equilibrium equations for this 2D foam when the solid
      surface is curved and smooth, generalising the standard case of flat Hele-Shaw
      cells. The equilibrium conditions at the vertices in 2D, at the edges in 3D, are
      invariant by conformal transformations. Regarding the films, conformal invariance
      only holds with restrictions, which we explicit for 3D and flat 2D foams.
      Considering foams confined in thin interstices between two non-parallel plates,
      normal incidence and Laplace's law lead to an approximate equation relating the
      plate profile to the conformal map. Solutions are given for the logarithm and
      power laws in the case of constant pressure. The paper concludes on a comparison
      with available experimental data.

PMID- 15875093
TI  - Risedronate decreases fracture risk in patients selected solely on the basis of
      prior vertebral fracture.
AB  - The aim of this study was to examine the effects of risedronate (5 mg/daily) in
      patients identified solely on the basis of a prior fragility fracture, without
      BMD as an inclusion criterion. A total of 1,802 patients were examined from the
      VERT-NA and VERT-MN clinical trials. Lateral radiographs (T4 to L4) were obtained
      at baseline and annually; incident fractures were evaluated using quantitative
      and semiquantitative methods at the central facility. BMD was measured at the
      lumbar spine and femoral neck by dual-energy X-ray absorptiometry. Secondary
      analyses evaluated vertebral fracture efficacy in patient subgroups categorized
      according to the presence of risk factors for osteoporosis at baseline (age,
      femoral neck BMD, lumbar spine BMD, more severe BMD, height, weight, body mass
      index, prevalent nonvertebral fracture status, smoking, and bone turnover marker
      levels). Over 3 years, risedronate reduced the risk of new vertebral fractures by
      44% (95% CI, 28% to 56%) compared with placebo. In patients subgrouped according
      to the presence or absence of putative risk factors, the efficacy of risedronate
      was comparable across all groups (all treatment-by-non BMD subgroup interactions
      p > or =0.210). Adjustment for age, baseline BMD, and prevalent vertebral
      fractures on fracture risk gave results similar to the unadjusted analysis. In
      patients taking placebo, the incidence of new vertebral fracture was higher in
      several of the high-risk categories (elderly, T-score < or = -2.5 SD). In
      conclusion, the findings of this study suggest that risedronate is effective in
      patients identified solely on the basis of a prior fragility fracture and that
      the efficacy of risedronate in the reduction of vertebral fractures is largely
      independent of the presence of clinical risk factors for osteoporotic fracture.

PMID- 15875094
TI  - Association of low general health status, measured prospectively by Euroqol EQ5D,
      with osteoporosis, independent of a history of prior fracture.
AB  - OBJECTIVES: There have been no studies of generic health-related quality of life
      (HR-QOL) measured prospectively, in patients referred for bone mass measurement.
      The aim of this study was to examine the relationship between HR-QOL, measured
      before DXA scanning was undertaken, and bone mineral density (BMD). Comparison of
      HR-QOL with the age- and sex-matched general population was also made. DESIGN: HR
      QOL questionnaires were completed by patients who were being entered into a
      randomized, prospective, parallel group trial to assess the impact of direct
      access DXA scanning (DADS) versus referral to a hospital consultant, upon
      clinical decision making by general practitioners (GPs) (Dhillon et al.,
      Osteoporos Int 14:326-333, 2003). HR-QOL questionnaires were completed prior to
      both randomization and DXA scanning. PARTICIPANTS: 325 patients from 18
      representative general practices of a total of 77 in the city of Edinburgh.
      Patients had been referred by their GPs who had access to national guidelines on
      the identification of patients at high risk of osteoporosis. OUTCOME MEASURES:
      Generic HR-QOL was measured using Euroqol (EQ5D). This provides a profile of self
      reported problems in five dimensions (EQ5D(profile)), health utility
      (EQ5D(utility)), and a visual analogue global self-rated health assessment
      (EQ5D(vas)). RESULTS: Odds ratios (ORs) for any self-reported problems on
      EQ5D(profile) were higher in patients with osteoporosis than those without, and
      compared with the general population. Age-adjusted mean (SD) EQ5D(utility )was
      significantly lower in patients with osteoporosis than in those without (0.65
      [0.28] vs 0.76 [0.27]; p< 0.01), but the difference lessened with advancing age.
      Age-adjusted mean (SD) EQ5D(vas) was significantly reduced in patients with
      compared with no osteoporosis (68 [20] vs 76 [16]; p<0.01). There were no such
      differences in patients with a history of prior fracture compared with those
      without a history of prior fracture. CONCLUSIONS: Female patients with
      osteoporosis have reduced generic HR-QOL compared with the age-matched female
      general population, irrespective of a history of prior fracture. The causal
      relationship between osteoporosis and HR-QOL, if any, is unclear. Further studies
      are needed to define this relationship and to determine whether treatment of
      osteoporosis has a beneficial effect on HR-QOL independent of fracture risk.

PMID- 15875095
TI  - ICD therapy in coronary artery disease. A reappraisal in 2005.
AB  - 25 years after the first coronary artery patient received an implantable
      cardioverter defibrillator (ICD), many randomized controlled trials on
      prophylactic ICD therapy have been conducted. Taken together, these trials allow
      an evidence-based approach to primary prevention of sudden cardiac death in
      patients after a myocardial infarction. Patients with chronic ischemic
      cardiomyopathy, a long history of heart failure, and an ejection fraction of < or
      = 0.30 benefit from preventive device therapy and are thus candidates for
      prophylactic defibrillator implantation. For this purpose, a single-chamber
      device appears to be appropriate, since there have been no prospective studies
      showing convincing clinical benefit by adding an atrial lead. For similar
      patients who have additional intraventricular conduction delays, a biventricular
      ICD must be considered. However, this decision must be based on individual
      considerations until more data from prospective trials become available.
      Prophylactic ICD therapy should not be used in patients with recent myocardial
      infarction. There is convincing evidence that ICD benefit in coronary patients
      accrues after a considerable time having elapsed from the most recent infarct,
      presumably at least 6 months or perhaps longer.

PMID- 15875096
TI  - [Idiopathic dilated cardiomyopathy--an appraisal in 2005].
AB  - Patients who present with an impaired left ventricular (LV) function of
      nonischemic origin (EF < or = 35%), should first undergo intensified heart
      failure therapy with angiotensin-converting enzyme (ACE) inhibitors, beta
      blockers and diuretics. If the impairment of LV function persists for 3-9 months
      despite adequate therapy, the implantation of a defibrillator (ICD) seems to be
      reasonable for the primary prevention of sudden cardiac death in these patients.
      If patients present with non-sustained ventricular tachycardias, ICD implantation
      and treatment with amiodarone are probably equally effective and better than mere
      heart failure therapy. In patients presenting with an indication for
      biventricular pacing, a biventricular ICD should be used.

PMID- 15875097
TI  - Arrhythmogenic right ventricular cardiomyopathy. Antiarrhythmic drugs, catheter
      ablation, or ICD?
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of sudden
      cardiac death and ventricular tachyarrhythmias in young, apparently healthy
      individuals and athletes. Myocardial atrophy with subsequent fibrofatty
      replacement predominantly affects right ventricular myocardium and results in
      global and regional dysfunction as well as areas of slow conduction and
      dispersion of refractoriness which are prerequisites for reentrant ventricular
      tachyarrhythmias. Patients affected with ARVC should be excluded from competitive
      sports and vigorous training. To provide optimal treatment, a detailed diagnostic
      evaluation and risk stratification are mandatory. Tailored treatment strategies
      aim at the suppression or effective termination of recurrent ventricular
      tachyarrhythmias and prevention of sudden death by antiarrhythmic drug therapy,
      catheter ablation, or implantation of a cardioverter defibrillator (ICD).
      Antiarrhythmic drugs may be used as a stand-alone treatment to suppress
      ventricular tachycardia (VT) recurrences in patients with ARVC and low risk of
      sudden death. Sotalol (preferred) or amiodarone in combination with beta-blockers
      showed the highest efficacy rates. In patients at higher risk, an ICD should be
      implanted and antiarrhythmic drugs be used only as an adjunct to prevent or
      suppress frequent VT recurrences and ICD discharges. Catheter ablation using
      conventional or electroanatomic mapping techniques yields good acute results for
      eliminating the targeted arrhythmia substrate. However, during the progressive
      long-term course of ARVC, VT recurrences from new arrhythmia foci are frequent
      and therefore limit the curative value of catheter ablation. In patients with
      frequent VT recurrences and ICD discharges, however, catheter ablation plays an
      important role as a palliative and adjunctive treatment option for arrhythmia
      suppression. ICD therapy has been increasingly used for secondary and also
      primary prevention of sudden death in patients with ARVC. In secondary
      prevention, the ICD has shown to improve the long-term prognosis of patients at
      high risk of sudden death by effective termination of life-threatening
      recurrences of ventricular tachyarrhythmias. However, adequate lead placement may
      be difficult and lead-related complications during long-term follow-up must be
      taken into account. The role of ICD therapy for primary prevention of sudden
      death in ARVC is not yet adequately defined. Ongoing international registries
      will provide important additional data to improve risk stratification and refine
      treatment algorithms in order to select the best individual treatment for
      arrhythmia suppression and prevention of sudden death in patients with ARVC.

PMID- 15875098
TI  - [Interventional treatment in hypertrophic cardiomyopathy].
AB  - Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease phenotypically
      expressed in the general population at about 0.2%. Annual mortality rate is about
      1% in unselected patients, 3-6% in patients with severe symptoms, and 17%
      following resuscitation from ventricular tachycardia (VT)/ventricular
      fibrillation (VF). 50-80% of deaths are sudden. Beneath effective treatment in
      severe symptoms of heart failure (most common in midlife and beyond) the
      prevention of sudden death (most common in young patients) continues to be a
      major challenge. The highest risk has been associated with any of the following
      markers: 1. prior cardiac arrest or spontaneous sustained VTs, 2. a family
      history of premature HCM-related death, 3. extreme left ventricular hypertrophy
      (> or = 30 mm), 4. syncope, 5. multiple bursts of nonsustained VTs, 6.
      hypotensive blood pressure response to exercise, and 7. marked septal scarring
      (hyperenhancement in magnetic resonance imaging). Treatment options in patients
      with drug-refractory symptoms or increased risk of sudden death are surgical
      myectomy, transcoronary ablation of septal hypertrophy (TASH), dual-chamber
      pacing, ablation of atrial fibrillation (or the AV node), and the implantable
      cardioverter defibrillator (ICD). 1. Surgical myectomy effectively improves
      symptoms, hemodynamics and probably prognosis. Long-term results are well known,
      but patients' preference and the number of experienced surgical centers are
      fading. Randomized studies are missing. 2. TASH induces quite similar
      improvements in symptoms and hemodynamics. It is remarkably evaluated for a
      postprocedural follow-up of up to 10 years, and it is the preferred mode of
      treatment in patients. However, information on long-term prognosis, rhythmogenic
      effects and randomized studies are missing. For the prevention of sudden death,
      TASH has to be combined with an ICD. 3. Dual-chamber pacing was evaluated in
      randomized crossover studies, but symptomatic and hemodynamic improvements and
      patients' preference are substantially lower than for TASH. 4. The ICD has the
      potential to alter prognosis in secondary (class I indication) and primary
      prevention. HCM patients should undergo a risk stratification assessment.
      Prophylactic implants base on a clinical profile with two or more risk markers
      (sometimes one risk marker). 5. Ablation of atrial fibrillation or the AV node is
      indicated to improve symptoms in patients with fast ventricular rates despite
      medical treatment. For the prevention of sudden death, it has to be combined with
      an ICD.

PMID- 15875099
TI  - [Long QT syndrome and Brugada syndrome. Drugs, ablation or ICD?].
AB  - Long QT syndrome and Brugada syndrome are potentially fatal inherited
      arrhythmogenic diseases. Thanks to the contribution of molecular genetics, the
      genetic bases, pathogenesis, and genotype-phenotype correlation of both diseases
      have been progressively unveiled and shown to have an extremely high degree of
      genetic heterogeneity. The clinical manifestation of the diseases is also highly
      variable. Symptomatic patients experience ventricular tachyarrhythmias which may
      lead to recurrent syncope and/or sudden cardiac death. In long QT syndrome
      patients with syncope, therapy with beta-blockers has proven effective. When,
      despite beta-blocker treatment, arrhythmia-related symptoms continue to occur, an
      implantable cardioverter defibrillator is indicated. Such a device should also be
      implanted in resuscitated patients. In symptomatic patients with Brugada
      syndrome, the implantable cardioverter defibrillator is the only life-saving
      option. In asymptomatic patients with a Brugada ECG pattern, risk stratification
      has become of utmost importance in order to discover which patients really need
      definitive treatment.

PMID- 15875100
TI  - [Is an electrophysiological study always necessary before defibrillator
      implantation?].
AB  - An electrophysiological study (EPS) and a programmed ventricular stimulation
      (PVS) are strongly recommended and clearly indicated before the implantation of a
      cardioverter defibrillator (ICD), if patients present with a cardiac arrest and
      no structural heart disease or a hypertrophic cardiomyopathy. In these patients
      the prevalence of a curable cause of the cardiac arrest, such as accessory
      pathways or an idiopathic ventricular tachycardia (VT), is high and the ICD
      implantation may be avoided. The same is true for patients who present with a
      cardiac arrest and a short PQ interval or a delta wave. If patients present with
      wide-complex tachycardias and the diagnosis of VT is unclear, an EPS and PVS are
      also clearly indicated. If patients have syncope or nonsustained VTs and a
      structural heart disease, PVS may be used for risk stratification. However, EPS
      and PVS may be of little use in patients with a structural heart disease and an
      impaired left ventricular function after a survived cardiac arrest or an unstable
      VT, which makes them candidates for ICD implantation anyway.

PMID- 15875101
TI  - [Leisure-time sport activities and cardiac outpatient therapy in coronary
      patients].
AB  - BACKGROUND: Exercise intensity in coronary patients is controlled by heart rate
      measurements. Very few investigations have compared the maximum heart rate in
      cardiac outpatient groups, in leisure-time sport activities, and especially in
      swimming. PATIENTS AND METHODS: Within different exercise conditions 21 coronary
      patients, nine in well-compensated cardiac condition joining a training group and
      twelve joining the exercise group with lower intensity, without signs of heart
      failure, engaged in an incremental bicycle ergometry. A six-lead ECG was derived
      at the same time with a 24-h ECG. The performance tolerance was measured by the
      pulse limit derived in 20 patients; one patient failed to show signs of
      subjective or objective ischemia. During a 24-h ECG monitoring, the patients took
      part in a 1-h standardized cardiac outpatient program, a standardized swimming
      program 4 x 25 m, and a typical self-selected leisure-time activity. RESULTS: The
      patients showed a peak work capacity of 2.2 W/kg and a symptom-free work capacity
      of 1.3 W/kg. The derived upper heart rate limit was passed during swimming by 19,
      during leisure-time activity by 16, and during cardiac outpatient program by two
      patients. The maximum of the mean overriding the limit occurred in leisure-time
      activity. Signs of ischemia occurred during ergometry in 15, during swimming
      training in ten patients, during leisure-time activity in eight, and during
      cardiac outpatient therapy in one. Arrhythmia < Lown IVa was documented on the
      ergometer in 15, during leisure-time sport activity in 15, during cardiac
      outpatient therapy in 17, and during swimming in eight patients. Arrhythmia Lown
      IVa occurred in one patient each during ergometry, leisure sports, and during the
      night. CONCLUSION: Coronary patients are in danger to exercise beyond the pulse
      limit during swimming and other leisure-time sports and not during cardiac
      outpatient therapy. The upper heart rate limit should be observed during swimming
      and other endurance leisure-time activities, and is of little importance during
      cardiac outpatient therapy.

PMID- 15875102
TI  - Surgical management of an extracardiac total cavopulmonary connection in
      heterotaxy syndrome with isolated hepatic drainage.
AB  - The extracardiac modification for completion of a cavopulmonary connection has
      added a further option for direction of inferior vena cava and/or hepatic venous
      drainage to the pulmonary arteries. The authors describe a technique of isolating
      a hepatic vein and connecting it to the inferior caval vein in a side-by-side
      fashion prior to anastomosing it to the tubegraft in a patient with heterotaxy
      syndrome.

PMID- 15875103
TI  - Management of pericardial effusion the role of echocardiography in establishing
      the indications and the selection of the approach for drainage.

PMID- 15875105
TI  - Electrical alternans due to cardiac tamponade.

PMID- 15875106
TI  - [A paradigm change in German academic medicine. Merger and privatization as
      exemplified with the university hospitals in Marburg and Giessen].
AB  - 1. The intended fusion of the university hospitals Marburg and Giessen in the
      state of Hessia is "a marriage under pressure with uncalculated risk" (Spiegel
      2005). In the present political and financial situation it hardly appears to be
      avoidable. From the point of the view of the faculty of medicine in Marburg it is
      difficult to understand, that the profits of this well guided university hospital
      with a positive yearly budget should go to the neighboring university hospital
      which still had a fair amount of deficit spending in the last years.2. Both
      medical faculties suffer from a very low budget from the state of Hessia for
      research and teaching. Giessen much more than Marburg, have a substantial need
      for investments in buildings and infrastructure. Both institutions have a similar
      need for investments in costly medical apparatuses. This is a problem, which many
      university hospitals face nowadays.3. The intended privatisation of one or both
      university hospitals will need sound answers to several fundamental questions and
      problems:a) A privatisation potentially endangers the freedom of research and
      teaching garanteed by the German constitution. A private company will undoubtedly
      influence by active or missing additional support the direction of research in
      the respective academic institution. An example is the priorisation of clinical
      in contrast to basic research.b) With the privatisation practical absurdities in
      the separation of research and teaching on one side and hospital care on the
      other will become obvious with respect to the status of the academic employees,
      the obligatory taxation (16%) when a transfer of labor from one institution to
      the other is taken into account. The use of rooms for seminars, lectures and
      bedside with a double function for both teaching, research and hospital care has
      to be clarified with a convincing solution in everyday practice.c) The potential
      additional acquisition of patients, which has been advocated by the Hessian state
      government, may be unrealistic, when the 4th biggest university hospital in
      Germany will be created by the merger. University hospitals recrute the patients
      for high end medicine beyond their region because of the specialized academic
      competence and advanced technical possibilities. Additional recruitment of
      patients for routine hospital can hardly be expected.d) A private management will
      have to consider primarily the "shareholder value", even when investing in
      infrastructure and buildings, as it can be expected for one partner. On the
      longterm this will not be possible without a substantial reduction of employees
      in both institutions. There are, however, also substantial efforts of some
      private hospital chains in clinical research, e. g. by Helios in Berlin and Rhon
      Gmbh at the Leipzig Heart Center.e) There is a yet underestimated but very
      substantial risk because of the taxation for the private owner when academic
      staff is transferred from the university to hospital care in their dual function
      as academic teachers and doctors. This risk also applies for the university if
      the transfer should come from hospital to the university. These costs would add
      to the financial burden, which has to be carried in addition to the DRGs.

PMID- 15875107
TI  - Prophylactic ICDs: can (and will) the medical marketplace decide their role?

PMID- 15875108
TI  - Dual site right atrial pacing can improve the impact of standard dual chamber
      pacing on atrial and ventricular mechanical function in patients with symptomatic
      atrial fibrillation: further observations from the dual site atrial pacing for
      prevention of atrial fibrillation trial.
AB  - BACKGROUND: The effects of atrial pacing mode on atrial and ventricular function
      in patients with atrial fibrillation (AF) and bradycardia have not been
      evaluated. We evaluated atrial and ventricular function during randomization to
      support pacing (SP), high right atrial pacing (HRA), and dual site right atrial
      pacing (DAP). METHODS: Seventy-nine patients (66 +/- 12 yr, 46 male) with
      standard pacing indications and symptomatic AF were randomized to each of three
      pacing modes (DAP, HRA, SP) for 6 months in a crossover design. Echocardiographic
      studies were performed at enrollment and the end of each mode. Paired comparisons
      of atrial and ventricular function parameters were performed between each pacing
      mode and baseline. RESULTS: HRA pacing in DDDR mode resulted in increased left
      ventricular (LV) end systolic volume (78 +/- 42 vs. 60 +/- 31 ml, p = 0.001) and
      reduced LV ejection fraction (44 +/- 14 vs. 50 +/- 11%, p = 0.007) compared to
      baseline. These parameters did not change during DAP. DAP resulted in increased
      peak A wave velocity (75 +/- 19 vs. 63 +/- 23 cm/s, p = 0.003) and atrial filling
      fraction compared to baseline (0.47 +/- 0.15 vs. 0.38 +/- 0.13, p = 0.005).
      Atrial and ventricular function were similar between control and SP. CONCLUSION:
      DAP, but not HRA or SP, improved left atrial (LA) function in patients with AF
      and bradycardia. HRA pacing in DDDR mode resulted in LA dilatation and
      deterioration of LV function which was not observed with DAP.

PMID- 15875109
TI  - Hybrid therapy with right atrial catheter ablation and previously ineffective
      antiarrhythmic drugs for the management of atrial fibrillation.
AB  - BACKGROUND: Many patients with paroxysmal atrial fibrillation (AF) become
      refractory to antiarrhythmic drugs (AADs). Early studies suggested that linear
      catheter ablation in the right atrium may provide sufficient substrate
      modification to reestablish therapeutic efficacy of previously ineffective AADs.
      METHODS: This prospective before-after multicenter trial evaluated the safety and
      effectiveness of hybrid therapy that included right atrial catheter ablation
      coupled with a regimen of previously ineffective AADs on AF episode frequency and
      symptoms in drug refractory patients with paroxysmal AF. A standard linear lesion
      set (lateral, septal, isthmus) was used in all subjects. AF episode frequency,
      clinical arrhythmia symptoms, condition-specific (AFSS) and global health-related
      quality of life (SF-36) were assessed prior to ablation and at 6 months. RESULTS:
      Ninety-three subjects, refractory to an average 2.9 AADs at baseline, qualified
      for inclusion and underwent right atrial catheter ablation. Eighty-four subjects
      (90%) provided 6 month AF episode frequency data which demonstrated a significant
      decrease compared to baseline (3.4 vs. 9.5, p < 0.0001). Forty-nine subjects
      (58%) were considered a clinical success by virtue of achieving a pre-specified
      target level episode frequency reduction of 50% or greater. Substantial and
      statistically significant improvements were realized almost uniformly for all
      measured arrhythmia symptoms as well as for both quality of life measures. The
      incidence of major complications was 5.4%. CONCLUSIONS: The addition of right
      atrial catheter ablation to a regimen of previously ineffective AADs is
      associated with a significant reduction in the frequency, duration and severity
      of AF episodes and symptoms.

PMID- 15875110
TI  - Early experience with a computerized robotically controlled catheter system.
AB  - BACKGROUND: Recently, the use of robotic assisted surgery has been utilized in
      cardiac surgical procedures. The use of robotics may offer benefits in precision,
      stability and control of instruments remotely. We report early experience with a
      novel remote robotic catheter control system (CCS). METHODS: We used a
      computerized robotically controlled catheter system that enables the user to
      remotely manipulate the tip of a catheter precisely in three dimensions. We
      tested the robotic catheter control systems ability to navigate within the heart
      and to make precise, rapid and repeatable movements. We compared the CCS with the
      ability of a standard quadripolar steerable ablation catheter placed in a
      deflectable sheath to navigate and make precision movements. Twelve ex-vivo
      porcine hearts were utilized to permit accurate measurements of navigation and
      precision. Eight targets were selected for navigation and precision testing. Time
      was measured for the catheter to reach the predefined target from a specific
      starting point to test navigation. In addition, time was measured to contact a
      discrete 0.8 mm target in order to test precision. RESULTS: The use of the CCS
      reduced the time needed for both navigation (8.5 +/- 13.9 sec vs. 22.7 +/- 26.7
      sec, p = 0.002) and significantly decreased the time for precision targeting
      (10.1 +/- 6.9 sec vs. 29.6 +/- 26.4 sec, p < 0.001) in the specific RA and LA
      sites in the ex-vivo hearts. CONCLUSIONS: The use of a computerized robotically
      assisted catheter control system is feasible and shows promise in rapid precision
      movement of the catheter. Further study is needed to elucidate the role of such a
      system in-vivo and in patient specific catheter ablation and mapping.

PMID- 15875111
TI  - Ablation of atrial-ventricular junction tissues via the coronary sinus using cryo
      balloon technology.
AB  - INTRODUCTION: The coronary sinus (CS) can provide access to targets across and
      within the atrioventricular (AV) junction. METHODS: In 12 dogs (32 +/- 3 Kg),
      cryo balloons (10-19 mm) were applied to regions of the AV junction for 3 minutes
      at a temperature of -75.9( composite function) +/- 9(composite function)C
      (ranging -57 to -83). Electrical activity and pacing within the CS were assessed
      pre and post ablation and at least 3 months later in 9 dogs. In the 3 other dogs,
      hearts were examined immediately after cryo ablation. CS and circumflex
      angiography was performed pre and post ablation. The hearts, CS, and Cx were then
      examined for structural injury. The AV junction was sectioned and the hearts were
      immersed in Tetrazolium, and the lesions were inspected for transmurality across
      the AV groove. RESULTS: In 3/12 dogs the distal CS cryo lesions resulted in
      inferior ST segment depression that resolved within 5 minutes. There was no
      arrhythmia or hemodynamic changes. No CS electrical activity was noted post
      ablation. The pacing threshold increased from 2 +/- 2.3 mA to 7.4 +/- 3.6 mA (p <
      0.001). Pathological examination of 3 acute hearts revealed hematomas. There was
      no pericardial effusion. No evidence of stenosis or thrombosis was seen within
      the CS and the circumflex artery. After 3 months of recovery, transmural lesions
      across the AV groove were present in all of the targeted AV regions. CONCLUSION:
      Intra-CS cryo balloon ablation is safe and can potentially replace endocardial RF
      ablation targeting the AV junction and the CS muscular sleeve.

PMID- 15875112
TI  - Survey of physician experience, trends and outcomes with atrial fibrillation
      ablation.
AB  - OBJECTIVE: We evaluated the prevalence, trends, outcomes and the general
      experience of physicians performing atrial fibrillation ablation (AF-ABL) in the
      United States (US). BACKGROUND: AF-ABL is a non-pharmacological and potentially
      curative therapy for AF. Success rates for AF-ABL have been reported to be
      between 80 and 90%. Although there are numerous clinical trial addressing this
      therapy little is known about the general status of AF-ABL in clinical practice.
      METHODS: We administered a mailed survey to the physician members of a
      professional arrhythmia society (Heart Rhythm Society, formerly known as the
      North American Society of Pacing and Electrophysiology) who practiced in the US
      (n = 1843). RESULTS: There were 304 responses, 66% (n = 204) performed ABL and
      30% (n = 92) performed AF-ABL. The study group performed a total of 5,592 AF-ABL
      from 2000 to 2003, out of 72,575 total ABL procedures during the same time
      period. There was a four-fold increase in the number of AF-ABL between 2000 and
      2003 (2000: 628 vs. 2003: 2,575). In the same period, the self-reported short and
      long-term success rates of AF-ABL improved an average of 18 +/- 4% (p < or =
      0.001). In 2003 the average self-reported one-month, one-year, and two-year
      success rates were: 71 +/- 4%, 66 +/- 5%, 63 +/- 6% respectively. The predicted
      five-year success was 60 +/- 4%. The average procedure took 4.5 +/- 0.4 hours.
      Physicians reported that approximately 29 +/- 4% of their patents were potential
      candidates for AF-ABL. CONCLUSIONS: AF-ABL is becoming a much more common
      procedure in the US. Over the last four years the perceived short and long term
      success rates of AF-ABL have improved. Success rates in this survey are 10 to 20%
      lower than those reported in the recent clinical trials.

PMID- 15875113
TI  - Pulsus alternans caused by 2:1 left bundle branch block.
AB  - Pulsus alternans was caused by 2:1 left bundle branch block in a patient with a
      left ventricular ejection fraction of 50% and normal coronary arteries. The
      observations documented the profound depressant hemodynamic effect of complete
      left bundle branch block in the setting of minimal systolic left ventricular
      function.

PMID- 15875114
TI  - Profound independent effects of left bundle branch block and heart rate during
      supraventricular tachycardia.
AB  - Left bundle branch block (LBBB) has negative hemodynamic effects. In the same
      patient, profound hypotension occurs during supraventricular tachycardia with
      LBBB but not at the same rate in the absence of LBBB. At slower rates, blood
      pressure is similar with and without LBBB.

PMID- 15875115
TI  - Atrioventricular nodal reentrant tachycardia with advanced infra-hisian
      atrioventricular block.
AB  - We report a case of 78-year-old man admitted to the hospital due to palpitations
      and lightheadedness. On EKG advanced atrioventricular block with ventricular rate
      of 37 beats per minute was noted. On electrophysiology study a common type of
      atrioventricular nodal reentrant tachycardia was inducible with maintenance of
      advanced AV block. Radiofrequency ablation of slow pathway followed by placement
      of a permanent pacemaker resulted in elimination of tachycardia and resolution of
      symptoms.

PMID- 15875116
TI  - New-onset ventricular tachycardia after cardiac resynchronization therapy.
AB  - It is well established that coronary artery disease with healed myocardial
      infarction is the most common backdrop for ventricular tachycardia (VT). Although
      the clinical benefits of biventricular pacing (BivP) in the treatment of severe
      heart failure are well documented, exact relation with ventricular arrhythmias
      remains still unclear. We describe a case of a patient, whitout a previous
      history of arrhythmic episodes, in which the onset of several episodes of VT
      presented immediatly after cardiac resynchronization therapy (CRT) and did not
      occur after BivP discontinuation.

PMID- 15875117
TI  - Interference by cellular telephone with an implantable loop recorder.
AB  - We report the observation of interference between an implanted loop recorder and
      a cellular telephone when the latter was placed over the subcutaneous pocket. The
      artifact produced during the ringing of the telephone was automatically recorded
      and stored in the device memory. A similar interference was documented during ex
      vivo testing.

PMID- 15875118
TI  - A combination of two simultaneous tachycardias in the right atrium close to the
      atrio-ventricular node and within the coronary sinus in a post-operative cor
      triatriatum patient.
AB  - A 71-year-old male was referred to another hospital for dizziness. A bradycardia 
      tachycardia syndrome and Cor triatriatum were detected, and an operation to
      resect the membrane in the left atrium and implant a pacemaker epicardially was
      performed. However, no suitable site could be found on either atria and
      therefore, a single chamber ventricular pacemaker was implanted. In the
      electrophysiological study performed in our hospital, we could not detect any
      atrial potentials in either atria, excluding the region close to the His bundle
      (HB) and within coronary sinus (CS), in spite of extensive catheter mapping. A
      regular atrial rhythm with a cycle length of 820 ms, which was synchronous with
      the rate of the QRS complex on the surface ECG, was recorded only at the HB.
      Meanwhile, the CS catheter recording exhibited regular focal activity with a
      cycle length of 150 ms, and this focal activity did not conduct to the atrium
      close to the HB. Furthermore, this activity was dissociated from the ventricular
      activity recorded from the CS catheter. During an isoproterenol infusion, an
      atrial tachycardia with a cycle length of 380 ms was recorded only at the HB, and
      the twelve-lead ECG exhibited a regular tachycardia with the same cycle length as
      this tachycardia. Meanwhile, the focal activity within the CS persisted without
      any change in the cycle length. These findings suggested that there was
      dissociation between the right atrium (RA) and CS. Furthermore, partial atrial
      standstill was observed in both atria, excluding the RA close to the atrio
      ventricular (AV) node and area within the CS. These rare electrophysiological
      features were considered to play an important role in the genesis of a
      simultaneous combination of the two tachycardias at their respective sites.

PMID- 15875122
TI  - Time is not up: temporal complexity of older Americans' lives.
AB  - The clock-dominated American discourse of time contributes to creating an image
      of the elderly as useless people who sit idly and wait to die. This article
      challenges such negative views of old age and illustrates the temporal complexity
      of older Americans' lives. It discusses various ways they cope with the tyranny
      of the clock and the dialectic relationships among the past, the present, and the
      future, as well as their meanings in old age. My examination reveals three major
      points. First, clock time is not as objective as is generally assumed but is
      imbued with tensions and contradictions. Second, the dominance of clock time does
      not eliminate other forms of time (e.g., cyclical, pendular, static), and older
      Americans live in multiple temporalities. Third, the elderly are active players
      with time, not only shaped by time, but also shaping time. The ethnographic data
      for this article derive from my long-term fieldwork at a senior center from 1987
      to the present.

PMID- 15875124
TI  - Delayed discharge and acceptability of ambulatory surgery in adult outpatients
      receiving general anesthesia.
AB  - PURPOSE: Delay in discharge after ambulatory surgery impairs its cost
      effectiveness. However, it is not self-evident that prolonged postoperative stay
      is associated with low quality of care and patient acceptability of ambulatory
      surgery. The aims of this study were to document factors affecting delay in
      discharge, recovery profiles, and patient acceptability in adult outpatients.
      METHODS: Perioperative data were collected prospectively on consecutive 726 adult
      same-day surgical patients receiving general anesthesia. Factors that affected
      home-readiness, discharge, and unanticipated admission were noted. Patients were
      followed up 24 h after discharge using a standardized questionnaire to identify
      postdischarge symptoms, patient's self-rated resumption of normal activity (RNA)
      level, and preference of outpatient procedure. RESULTS: Eighty-two percent of
      patients were discharged home <270 min after operation, 16% were delayed (> or =
      270 min), and 2% required unanticipated admission. Delayed patients reported
      postdischarge pain more frequently (53%) and a lower 24-h postoperative RNA level
      (7.2 +/- 1.8) and preference ratio (76%) than no-delay patients (34%, 8.0 +/-
      1.9, 87%, respectively; P < 0.001). Delay in home-readiness (> or = 165 min) was
      mainly due to an adverse symptom, and delay in discharge after reaching home
      readiness (> or = 150 min) was mainly due to a persistent symptom (58%) or a
      social/system problem (34%). Causes of admission were perioperative complications
      (80%) or social reasons (20%). CONCLUSION: Delays in discharge are mainly due to
      adverse symptoms or social/system problems. Delayed discharge is associated with
      increased postdischarge pain, lower RNA level, and patient acceptability.
      Appropriate care of postoperative symptoms and system management could prevent
      delay in discharge and improve patient RNA level and acceptability.

PMID- 15875123
TI  - Post-retirement voluntary work and psychological functioning among older Chinese
      in Hong Kong.
AB  - This study examined demographic and psychosocial differences between older
      Chinese volunteers and non-volunteers. The influences of work-related factors on
      older Chinese volunteers' post-retirement psychological functioning and life
      satisfaction were also explored. A total of 501 older Chinese in Hong Kong were
      individually interviewed. About 65% of them were involved in community voluntary
      work since their retirement, with an average of four hours per week. Compared to
      those without voluntary work experiences, older Chinese volunteers had higher
      educational attainment and reported better physical health, higher self-efficacy,
      greater life satisfaction, and less psychological distress. Results from
      hierarchical regression analyses showed that salient correlates of a low level of
      psychological distress in older Chinese volunteers were high educational
      attainment, high self-efficacy, perceived good physical health, and high levels
      of perceived rewards and satisfaction from voluntary work. Self-efficacy and
      perceived rewards from voluntary work were also salient correlates of life
      satisfaction for older Chinese volunteers. As hypothesized, work-related factors
      of perceived rewards and work satisfaction remained significant correlates of
      older volunteers' psychological well-being, even after controlling for
      demographic and individual psychosocial factors. Limitations and implications of
      the study were also discussed.

PMID- 15875125
TI  - The bispectral index predicts responsiveness to verbal commands in patients
      emerging from nitrous oxide anesthesia supplemented with a subhypnotic
      concentration of isoflurane.
AB  - PURPOSE: Nitrous oxide (N2O) administered alone has minimal effects on the
      bispectral index (BIS), an electroencephalogram-derived parameter of hypnosis.
      However, because this gas is commonly supplemented with a volatile anesthetic, we
      sought to determine how it would affect the BIS when coadministered with a low
      concentration of isoflurane. METHODS: Twelve patients were anesthetized with 70%
      N2O + 0.2% isoflurane (all concentrations are end-tidal). Following the end of
      surgery, the concentration of N2O was decreased in decrements of 10% while
      isoflurane was continued at 0.2%, and each new concentration of N2O was
      maintained for 15 min. This procedure was repeated until the patients first
      opened their eyes or squeezed the investigator's hand on command. RESULTS: N2O
      70% + isoflurane 0.2% reduced the BIS to 68 +/- 9 (mean +/- SD). When the
      concentration of N2O was decreased toward awakening (which occurred at the N2O
      concentration of 36% +/- 8%), the BIS progressively increased until it reached 93
      +/- 5 on awakening. CONCLUSION: The BIS reflects the level of hypnosis during N2O
      anesthesia supplemented with a low concentration of isoflurane.

PMID- 15875126
TI  - Noninvasive assessment of left ventricular pressure-area relationship using
      transesophageal echocardiography and tonometry during cardiac and abdominal
      aortic surgery.
AB  - PURPOSE: The purpose of this study was to noninvasively evaluate intraoperative
      left ventricular (LV) performance by an online pressure-area relationship using
      transesophageal echocardiography (TEE) and tonometry. METHODS: In study 1, LV
      pressure with a micromanometer catheter, LV cross-sectional area with TEE, direct
      radial pressure, and tonometric arterial pressure were simultaneously recorded in
      5 patients (10 measurements) undergoing cardiac surgery. End-systolic elastance
      (E'es) was determined from pressure-area loops during inferior vena caval (IVC)
      occlusion. In study 2, in 16 patients undergoing repair of abdominal aortic
      aneurysm, LV performance (E'es; effective arterial load, E'a, and LV end
      diastolic area, LV-EDA) was examined by noninvasive assessment of pressure-area
      loops using TEE and tonometry at aortic cross-clamping and unclamping. RESULTS:
      E'es by tonometric arterial pressure closely correlated with E'es by LV pressure
      (r = 0.92) in study 1. E'es at aortic clamping were not significantly different
      from those at unclamping. The clamping increased LV-EDA and E'a by approximately
      13% and 44%, and the unclamping significantly decreased by 9% and 22%,
      respectively. CONCLUSION: Our results demonstrated that online tonometric
      arterial pressure and LV area measured by automated border detection (ABD) of TEE
      might be used to calculate E'es to estimate LV contractility and allow the
      estimation of LV performance during aortic clamping and unclamping.

PMID- 15875127
TI  - Laryngeal mask airway can be inserted with inhaled desflurane induction.
AB  - PURPOSE: In this prospective, randomized, controlled trial, we investigated the
      reliability of laryngeal mask airway (LMA) insertion with inhaled desflurane.
      METHODS: Eighty patients undergoing elective surgery were randomized into two
      groups to receive either 2.5 mg x kg(-1) propofol (n = 40) or tidal breath
      desflurane (n = 40) induction followed by LMA insertion. All patients received
      fentanyl 1 microg x kg(-1) 2 min before induction. Inhalation of desflurane was
      started at 3% and increased by 3% every 3-5 breaths up to settings of 12%.
      RESULTS: Insertion of the LMA was faster in the propofol group (131.8 s versus
      228.6 s, P < 0.01). The number of patients in whom the jaw opening was described
      as good (95% versus 72.5%, P = 0.27, for the desflurane and propofol groups,
      respectively) and the ease of LMA insertion described as good (87.5% versus
      72.5%, P = 0.6) were comparable. The LMA was inserted in a single attempt in the
      majority of patients in both groups (80% versus 77.5%, P = 0.90). There were more
      complications at insertion in the propofol group than in the desflurane group
      (2.5% versus 19.5%, P < 0.01), especially for apnea (7.5% versus 70%, P < 0.01)
      and excitatory movements (2.5% versus 25%, P < 0.01). There were significant
      decreases in the mean arterial pressure in the propofol group compared to
      baseline data over the first 5 min of induction. Mean arterial pressure, heart
      rate, and S(p)(O2) remained stable during the same period in the desflurane
      group. CONCLUSION: We demonstrated that inhaled desflurane when used with caution
      in a controlled manner provided acceptable conditions for LMA insertion.

PMID- 15875128
TI  - Risk factors for prolonged ICU stay in patients following coronary artery bypass
      grafting with a long duration of cardiopulmonary bypass.
AB  - PURPOSE: Risk factors for prolonged stay in the intensive care unit (ICU) in
      patients following coronary artery bypass grafting (CABG) have been reported in
      many previous studies. However few have focused on circulatory and respiratory
      status as immediate postoperative risk factors. Therefore we examined immediate
      postoperative risk factors for prolonged ICU stay after CABG with a long duration
      of cardiopulmonary bypass (CPB). METHODS: We studied retrospectively 100
      consecutive patients undergoing elective CABG with CPB. Patients were excluded
      from this study if the duration of aortic cross-clamping was less than 60 min.
      Patients were divided into three groups according to the duration of the ICU
      stay. Patients in group A (n = 68) were discharged from the ICU on the next
      morning after surgery, those in group B (n = 19) stayed for 3 days, and group C
      (n = 13) stayed for more than 3 days. Perioperative variables were compared among
      the three groups and we demonstrated risk factors for prolonged (more than 3
      days) ICU stay. RESULTS: There were significant differences in duration of CPB
      (157 +/- 34 versus 184 +/- 48 minutes, P < 0.05) and aortic cross-clamping (119
      +/- 32 versus 141 +/- 40 min) between groups A and B. On the other hand, there
      were significant differences in age (62.8 +/- 7.8 versus 67.4 +/- 6.2 years),
      mean pulmonary artery pressure (MPAP) (17 +/- 2 versus 22 +/- 3 mmHg), and
      Pa(O2)/FI(O2) (PF ratio) (409 +/- 94 versus 303 +/- 108 mmHg) on admission to the
      ICU between groups A and C. There were no significant differences in
      intraoperative fluid balance and duration of CPB. Multiple logistic regression
      analysis identified age (>65 years), MPAP (>21 mmHg), and PF ratio (<300 mmHg) as
      independent risk factors for more than a 3-day ICU stay. CONCLUSION: Advanced
      age, increased MPAP, and decreased PF ratio on admission to the ICU were
      significant risk factors for a prolonged ICU stay of more than 3 days.

PMID- 15875129
TI  - Cardioprotective effects of KB-R7943, a novel inhibitor of Na+/Ca2+ exchanger, on
      stunned myocardium in anesthetized dogs.
AB  - PURPOSE: The present study was carried out to determine the cardioprotective
      effects of KB-R7943 (KBR), a selective inhibitor of the reverse mode of Na+/Ca2+
      exchanger (NCX), on stunned myocardium in anesthetized dogs. METHODS: The dogs
      were allocated to one of three groups (n = 7 for each group), and received drug
      vehicle (group C), low-dose KBR (5 mg x kg(-1) i.v.) (group L) or high-dose KBR
      (10 mg x kg(-1) i.v.) (group H) at 15 min before left anterior descending
      coronary artery (LAD) occlusion. Stunned myocardium was produced by 15-min
      occlusion of LAD and 90-min reperfusion in all dogs. Regional myocardial
      contractility was evaluated with segment shortening (%SS). RESULTS: Recovery of
      %SS at 90 min after reperfusion was significantly improved in group H (70.8% +/-
      3.9% of baseline), whereas the recovery was poor in groups C and L (34.3% +/-
      2.8% and 36.4% +/- 5.4% of baseline, respectively). Regional myocardial blood
      flow showed no significant difference among groups. KBR had no effect on coronary
      or systemic hemodynamics. CONCLUSION: The results show that preischemic
      administration of high-dose KBR markedly improves myocardial contractile
      dysfunction after ischemia-reperfusion in anesthetized dogs, indicating that KBR
      protects myocardium against the ischemia-reperfusion injury in vivo.

PMID- 15875130
TI  - Evaluation of dilators for central venous catheterization using an experimental
      model.
AB  - PURPOSE: Skin incision before percutaneous central venous catheterization may
      cause serious hemorrhage and/or skin cicatrization. To minimize these adverse
      effects, we improved the shape of a dilator and coated it with lubricant to
      reduce insertion load. METHODS: We selected three types of dilators from
      different manufacturers. Each brand was widely available on the market in Japan.
      We redesigned one model with modified multitapering angles. Six types of dilators
      in total (three manufactured dilators, one manufactured dilator with lubricant,
      and the newly modified dilator +/- lubricant) were examined regarding load of
      insertion using pork muscle covered with porcine skin. Among these dilators, two
      manufactured dilators and the newly modified one with lubricant were also
      investigated regarding insertion load with or without skin incision. RESULTS: The
      minimum load of insertion was observed in the newly modified dilator with
      lubricant. The modified dilator attenuated the insertion load by up to 50% of the
      manufactured dilator, and the lubricant also reduced load by up to 16%. The
      insertion load of the modified dilator coated with lubricant was comparable to
      that of the manufactured dilators inserted with a 2-mm skin incision. CONCLUSION:
      The lubricant-coated dilator with multitapering angles was associated with
      decreased insertion load and thus facilitated its insertion without skin
      incision.

PMID- 15875131
TI  - Negative inotropic action of propofol is enhanced in the acute ischemic
      myocardium of dogs.
AB  - PURPOSE: We investigated the effects of propofol on contractility and oxygen
      balance in acute ischemic myocardium and compared them with those of normal
      myocardium using a coronary microembolization model in dogs. METHODS: In open
      chest dogs, the left anterior descending coronary artery (LAD) was perfused
      through an extracorporeal bypass from the carotid artery. Regional myocardial
      contractility and myocardial oxygen balance were evaluated along with segment
      shortening (%SS), regional myocardial oxygen consumption (MVO2), and lactate
      extraction ratio (LER) of the area perfused by the LAD. Acute ischemia was
      produced by repeated injection of microspheres into the LAD-perfused area until
      %SS decreased by 50% of baseline. RESULTS: In normal myocardium, intracoronary
      infusion of propofol at doses of 1.2 and 2.4 mg x kg(-1) x h(-1) caused slight
      decreases in %SS to 83% +/- 8% and 80% +/- 10%, respectively. In ischemic
      myocardium, propofol caused greater decreases in %SS (59% +/- 18% and 35% +/-
      20%, respectively). The changes in MVO2 after propofol infusion generally
      paralleled the changes in %SS, but LER was not changed in either ischemic or
      normal myocardium. CONCLUSION: Propofol causes a greater decrease in the
      contractility of acute ischemic myocardium as compared with normal myocardium in
      which myocardial oxygen imbalance is not involved as a mechanism.

PMID- 15875132
TI  - Anesthesia management for electroconvulsive therapy: hemodynamic and respiratory
      management.
AB  - Recent guidelines have stated that anesthesia for electroconvulsive therapy (ECT)
      should be administered by a specially trained anesthesiologist, and that
      anesthesiologists have overall responsibility, not only for anesthesia itself,
      but also for cardiopulmonary management and emergency care. Accordingly,
      anesthesiologists who administer anesthesia for ECT should have sufficient
      knowledge regarding the physiologically and pharmacologically unique effects of
      ECT. Electrical current during ECT stimulates the autonomic nervous system and
      provokes unique hemodynamic changes in systemic and cerebral circulation.
      Excessive alterations in heart rate, blood pressure, and cardiac functions should
      be prevented by medications with anticholinergic and antihypertensive agents.
      Ventilation should be adequately maintained to ensure the efficacy of the therapy
      and to stabilize the hemodynamics immediately after the electrical stimulation.
      Reports of serious complications of this therapy are not frequent; however,
      patients with ischemic heart disease or cerebrovascular problems must be managed
      with special care to prevent myocardial infarction or neurological disorders.
      Safe physical management by anesthesiologists greatly contributes to the
      establishment of ECT under muscle relaxation. To maintain social confidence and
      to refine the therapy, anesthesiologists should play an essential role both in
      clinical activities and in laboratory research.

PMID- 15875133
TI  - Neuroprotective effects of anesthetic agents.
AB  - Ischemic neuronal injury is characterized by early death mediated by
      excitotoxicity and by delayed death caused by apoptosis. Current evidence
      indicates that volatile agents, barbiturates, and propofol can protect neurons
      against ischemic injury caused by excitotoxicity. In the case of volatile agents
      and propofol, neuroprotection may be sustained if the ischemic insult is
      relatively mild; however, with moderate to severe insults, this neuronal
      protection is not sustained after a prolonged recovery period. This suggests that
      volatile agents and propofol do not reduce delayed neuronal death caused by
      apoptosis. The long-term effects of barbiturates on ischemic cerebral injury are
      not yet defined. Cerebral ischemia is characterized by continued neuronal loss
      for a long time after the initial ischemic insult. Therefore, in investigations
      of cerebral ischemia, the duration of the recovery period should be taken into
      consideration in the analysis of the neuroprotective effects of anesthetic
      agents. A combination of different approaches that target specific stages of the
      evolution of ischemic injury may be required for sustained neuroprotection.

PMID- 15875134
TI  - Successful use of Shakuyaku-kanzo-to, a traditional herbal medicine, for
      intractable symptoms of thoracic outlet syndrome: a case report.
AB  - Shakuyaku-kanzo-to (SKT) is a traditional herbal medicine that is widely used for
      muscular cramp and abdominal pain. We administered SKT for a patient with
      thoracic outlet syndrome (TOS) complaining of several resting symptoms. A 28-year
      old female patient complained of intractable pain in the left arm, shoulder, and
      back and weakness, numbness, and muscular cramp in the left arm. She was
      diagnosed as TOS by digital subtraction angiography. Two days after the start of
      administration of SKT, her severe pain was markedly improved. Although numbness
      of the left arm was not improved, her overall pain score was reduced by 2 on the
      7th day after the start of SKT. SKT has several pharmacological effects including
      analgesic and antiinflammatory effects, vasodilation, and muscle relaxation.
      Thus, our report suggests that SKT could be a first-line agent for the
      conservative treatment of TOS.

PMID- 15875135
TI  - Nitrous oxide administration during washout of sevoflurane improves
      postanesthetic agitation in children.
AB  - The use of sevoflurane in pediatric patients, which could enable a more rapid
      emergence and recovery, is complicated by a high incidence of postanesthetic
      agitation, probably due to residual sevoflurane during washout. The present study
      was designed to investigate whether administration of nitrous oxide (N2O) reduces
      sevoflurane concentration at awakening and suppresses postanesthetic agitation.
      The study enrolled 20 children classified as ASA physical status I. Anesthesia
      was induced with 5% sevoflurane and maintained with 2.5% end-tidal sevoflurane
      and N2O in oxygen. In the control group, sevoflurane and N2O were discontinued
      immediately after completion of surgery. In the N2O group, inspired N2O was
      replaced with oxygen after the bispectral index (BIS) had reached 80. The end
      tidal concentrations of sevoflurane at awakening were significantly lower (P <
      0.05) in the N2O group than in the control group. The BIS at awakening was higher
      (P < 0.01) in the N2O group than in the control group. The point scores of
      postanesthetic agitation were significantly lower (P < 0.01) in the N2O group
      than in the control group. Using N2O during washing out of sevoflurane may
      improve postanesthetic agitation at awakening in children.

PMID- 15875136
TI  - Undisrupted pulse wave on pulse oximeter display monitor at cardiac arrest in a
      surgical patient.
AB  - We have encountered a case of cardiac arrest during anesthesia care in which an
      application of a new-generation pulse oximetry technology led to a misleading
      interpretation of the patient's true condition. Just after manipulation of the
      peritoneum, the heart rhythm suddenly became asystole, while the ECG showed a
      standstill and an arterial pressure wave was absent. However, the Datex-Ohmeda
      AS/3 Patient Monitor connected to the Masimo SatShare Waveform Generator feature
      continued to display a pulse wave with a reading of 99%. Because we assumed the
      reading to be reliable, we took no immediate action. However, the ECG standstill
      and flattened arterial wave lasted for about 10 s, with no pulse at the common
      carotid artery; thus, 0.5 mg atropine and 4 mg ephedrine were given and chest
      compression performed using ventilation with oxygen. About 20 s later, the heart
      rhythm reappeared, which was monitored by the ECG and arterial pulse wave. This
      incident demonstrates the importance of becoming familiar with a new technology;
      otherwise, we will fall into medical errors.

PMID- 15875137
TI  - Percutaneous radiofrequency lumbar facet rhizotomy guided by computed tomography
      fluoroscopy.
AB  - X-ray fluoroscopy-guided percutaneous radiofrequency facet rhizotomy is used to
      treat chronic low back pain. The traditional fluoroscopic approach to the medial
      branch of the posterior rami, however, is associated with a small incidence of
      complications. We describe a new method for radiofrequency lumbar facet rhizotomy
      in which computed tomography (CT) fluoroscopy is used to guide needle placement.
      Three patients with chronic intractable low back pain underwent CT fluoroscopy
      guided percutaneous facet rhizotomy. After the safest and shortest route to the
      target site was determined on the CT image, the needle was advanced along the
      predetermined route under real-time CT fluoroscopy. When the needle tip was
      located at the target site, electrical stimulation was applied to verify proper
      electrode placement. After confirming the clinical effect and lack of
      complications under test block with a local anesthetic, denervation was performed
      using radiofrequency current. Pain scores of all patients were reduced after the
      procedure without any complications such as paralysis or neuritic pain. None of
      the patients complained of severe discomfort during the procedure. CT fluoroscopy
      guided percutaneous lumbar facet rhizotomy appears to be safe, fast, and
      effective for patients with lumbar facet pain.

PMID- 15875138
TI  - Low-dose vasopressin infusion in patients with severe vasodilatory hypotension
      after prolonged hemorrhage during general anesthesia.
AB  - We report the successful use of a low-dose vasopressin (VP) infusion to recover a
      hypotensive crisis in patients who suffered persistent hypotension after
      prolonged hemorrhage during general anesthesia. VP was infused in two
      posthemorrhagic vasodilatory shock patients when they remained persistently
      hypotensive despite adequate fluid resuscitation and infusions of pharmacological
      doses of catecholamines. On administration of VP at 0.04 U x min(-1), systemic
      vascular resistance, systolic arterial pressure, and urine output were
      immediately increased (as compared with the values obtained just before VP), and
      infusion of catecholamine could be decreased. No adverse cardiac effects were
      observed during VP infusions in these patients. During vasodilatory shock after
      prolonged and severe hemorrhage, VP seems to be effective in reversing
      hypotension and decreasing the need for exogenous cathecholamines while
      preserving cardiac function and critical organ blood flow.

PMID- 15875139
TI  - Successful management of cesarean section in a patient with Romano-Ward syndrome
      using landiolol, a selective and short-acting beta1 receptor antagonist.
AB  - Romano-Ward (R-W) syndrome is an autosomal dominant hereditary disorder and is
      characterized by a prolonged QT interval on the electrocardiogram (ECG), syncope,
      and sudden death. We report here a case of cesarian section in a patient with R-W
      syndrome whose QT prolongation was successfully managed with landiolol, a
      selective beta1 receptor blocker. A 25-year-old woman with R-W syndrome was
      scheduled for cesarean section. In the operating room, the patient's ECG showed
      tachycardia (102 beats x min(-1)) and marked QT prolongation (QTc = 0.56 s).
      After spinal anesthesia, the patient's heart rate (HR) increased to 130 beats/min
      accompanied by a slight decrease in arterial blood pressure to 97/57 mmHg and the
      QTc was prolonged to 0.57 s. Landiolol was continuously infused at a rate of 0.04
      mg.kg(-1) x min(-1) and the HR gradually decreased to 80-90 beats x min(-1)
      accompanied by the normalization of QTc to 0.48 s. We thought that the use of
      landiolol was more rational and was preferable to a nonselective beta receptor
      blocker for a term-pregnant woman because blockade of the beta2 receptor might
      cause uterine contraction. After the use of landiolol, intraoperative and
      postoperative courses in both the patient and the baby were uneventful.

PMID- 15875140
TI  - Thermogangliolysis of the Gasserian ganglion under computed tomography
      fluoroscopy.
AB  - Gasserian ganglion block is an established treatment for trigeminal neuralgia. A
      landmark approach assisted by X-ray fluoroscopy is the most common method;
      however, visualization of the foramen ovale is difficult in some cases. Here we
      report two cases in which a novel technique using modern computed tomography (CT)
      fluoroscopy was employed. A 63-year-old woman suffering pain in the maxillary
      nerve area was treated by thermogangliolysis under CT fluoroscopy. The patient
      was positioned on a CT stage with the head in an overhanging position. The CT
      gantry was set at an oblique angle to obtain a coronal view of the foramen ovale.
      The safest and shortest route to the foramen was designed using the CT image and
      a 22-gauge insulated needle was advanced following the designed route under CT
      fluoroscopy. The effect of the nerve block was estimated by injection of a test
      dose of mepivacaine, after which the ganglion was thermally coagulated at 90
      degrees C. Satisfactory analgesia was obtained in this case without any
      complications. Another patient (65 years old) was also treated by the same
      technique, and satisfactory pain relief was obtained. In conclusion, CT
      fluoroscopy-guided Gasserian ganglion thermolysis is considered a safe, quick,
      and effective treatment for trigeminal neuralgia.

PMID- 15875141
TI  - Preadministration of low-dose ketamine reduces tourniquet pain in healthy
      volunteers.
AB  - We evaluated whether preadministration of low-dose ketamine could attenuate
      tourniquet pain and arterial pressure increase using high tourniquet pressure in
      ten healthy awake volunteers. Ketamine, 0.1 mg x kg(-1), or normal saline was
      given intravenously in a double-blind fashion before tourniquet inflation with a
      pressure of 400 mmHg at the thigh. Visual analog scale (VAS) scores and systolic
      blood pressure (SBP) were measured at 5-min intervals. Ketamine significantly
      reduced VAS scores compared to saline just after tourniquet inflation [90 (64
      100) mm, median (range), with saline versus 66 (50-81) mm with ketamine, P <
      0.01] and at 30 min [92 (61-100) mm with saline versus 70 (50-100) mm with
      ketamine, P < 0.03), and significantly prolonged tourniquet time (28 +/- 6 min
      with saline, mean +/- SD, versus 37 +/- 7 min with ketamine, P < 0.01). SBP (120
      +/- 9 mmHg) significantly increased before tourniquet deflation (133 +/- 16 mmHg)
      in the saline trial, but not in the ketamine trial. The results show that
      preadministration of low-dose ketamine attenuates tourniquet pain and arterial
      pressure increase during high-pressure tourniquet application and prolongs
      tourniquet time in healthy volunteers.

PMID- 15875142
TI  - Adequate shunt occlusion confirmed by near-infrared spectroscopy in a patient
      with arteriovenous malformation in the leg.

PMID- 15875143
TI  - A less-traumatic way of light-guided intubation with Parker Flex-Tip tube.

PMID- 15875144
TI  - Invasive annual grasses indirectly increase virus incidence in California native
      perennial bunchgrasses.
AB  - In California valley grasslands, Avena fatua L. and other exotic annual grasses
      have largely displaced native perennial bunchgrasses such as Elymus glaucus
      Buckley and Nassella pulchra (A. Hitchc.) Barkworth. The invasion success and
      continued dominance of the exotics has been generally attributed to changes in
      disturbance regimes and the outcome of direct competition between species. Here,
      we report that exotic grasses can also indirectly increase disease incidence in
      nearby native grasses. We found that the presence of A. fatua more than doubled
      incidence of infection by barley and cereal yellow dwarf viruses (B/CYDVs) in E.
      glaucus. Because B/CYDV infection can stunt E. glaucus and other native
      bunchgrasses, the indirect effects of A. fatua on virus incidence in natives
      suggests that apparent competition may be an additional mechanism influencing
      interactions among exotic and native grasses in California. A. fatua's influence
      on virus incidence is likely mediated by its effects on populations of aphids
      that vector B/CYDVs. In our study, aphids consistently preferred exotic annuals
      as hosts and experienced higher fecundity on them, suggesting that the exotics
      can attract and amplify vector populations. To the best of our knowledge, these
      findings are the first demonstration that exotic plants can indirectly influence
      virus incidence in natives. We suggest that invasion success may be influenced by
      the capacity of exotic plant species to increase the pathogen loads of native
      species with which they compete.

PMID- 15875145
TI  - [Modern imaging for liver metastases from colorectal tumors].
AB  - Cross-sectional imaging modalities such as ultrasound, computed tomography (CT),
      magnetic resonance imaging (MRI), and Positron emission tomography (PET)/CT have
      benefited from rapid technical advances in recent years. In patients with
      colorectal tumors, multislice CT is the standard technique for preoperative
      evaluation and follow-up. It is faster than single-slice helical CT and allows
      for excellent 3D imaging of liver anatomy and tumor volumetry. The most accurate
      technique for detecting and characterizing focal liver lesions is MRI using state
      of-the-art scanners and liver-specific contrast agents and should be used for
      preoperative evaluation of all possible surgical candidates. Whole-body FDG-PET
      and PET/CT are most useful in the detection of extrahepatic disease and may alter
      clinical management in up to 20% of patients by detecting extrahepatic spread of
      disease.

PMID- 15875146
TI  - [Abdomino-right-thoracic esophagectomy with intrathoracic anastomosis in
      Barrett's cancer].
AB  - The modified technique of abdomino-right-thoracic esophagectomy (the Lewis-Tanner
      approach) is increasingly being favoured as the surgical procedure of choice in
      patients with resectable adenocarcinoma of the distal esophagus, so-called
      Barrett's cancer. The technical details of this procedure and the reconstruction
      of gastrointestinal continuity using a gastric tube with high intrathoracic
      anastomosis are illustrated, as they have proved useful in our own practice
      during recent years.

PMID- 15875147
TI  - [Giardia lamblia--cause of urticaria and pruritus or accidental association?].
AB  - Three patients with chronic urticaria or pruritus were found to suffer from an
      asymptomatic intestinal infection caused by the protozoan Giardia lamblia.
      Treatment with metronidazole per os or tinidazole per os was successful; the
      pruritic symptoms in one patient improved markedly.Giardia lamblia (Giardia
      intestinalis) are enteroparasites and produce gastrointestinal symptoms such as
      acute and chronic diarrhea. Cutaneous manifestations associated with giardiasis
      occur extremely rarely. Urticaria and itching may be explained as an infection
      associated allergy. Hitherto, the following cutaneous signs have been described:
      urticaria, angioedema, mouth ulcers, pruritus, atopic dermatitis, and anal
      eczema.We considered that the cutaneous manifestations described here, i. e.,
      urticaria and itching, were secondary to the associated gastrointestinal
      infection due to Giardia lamblia cysts and trophozoite forms, as they disappeared
      under specific treatment with metronidazole or tinidazole.

PMID- 15875148
TI  - [Diverticulosis and diverticulitis].
AB  - Alterations in the colon wall, motility disorders, and certain nutritional habits
      are the essential factors in the development of colon diverticula. Thus, with
      advancing age this results in a high incidence in Western industrialized
      countries. The clinical picture is usually one of symptom-free diverticulosis.
      Diverticular disease can be associated with minor symptoms, but in complicated
      cases with diverticulitis and diverticular hemorrhage, it is potentially fatal.
      Further complications include abscess formation, fistula development, and
      obstruction. Barium double-contrast imaging exhibits the highest diagnostic
      sensitivity in diverticulosis but is contraindicated in cases of suspected
      complicated diverticular disease due to the danger of perforation. In these
      instances, sonography, computed tomography, or magnetic resonance imaging are
      performed. For diverticular hemorrhage, coloscopy not only represents a possible
      diagnostic tool but also a therapeutic option for various techniques of
      hemostasis. Treatment of diverticulitis and its complications requires careful
      consideration of conservative and surgical approaches and close interdisciplinary
      cooperation.

PMID- 15875149
TI  - More reactive and less reactive C-reactive protein.

PMID- 15875150
TI  - Hemojuvelin: a supposed role in iron metabolism one year after its discovery.
AB  - The discovery of hemojuvelin and its association with juvenile hemochromatosis
      are important not only for the diagnostics of this rare severe disease but also
      for the understanding of the complex mechanism of iron metabolism regulation.
      Currently, the physiological role of hemojuvelin is obscure. Recent experimental
      and clinical studies indicate that hemojuvelin will probably be a regulator of
      hepcidin, similar to HFE and transferrin receptor 2. However, in contrast to
      transferrin receptor 2, which is relevant in the hepcidin response to changes in
      transferrin saturation, HFE and especially hemojuvelin seem to be involved in the
      inflammation-induced hepcidin expression. Hepcidin, generally accepted as a
      hormone targeting enterocytes and macrophages, decreases iron absorption from the
      intestinal lumen and iron release from phagocytes. This mechanism explains the
      central role of hepcidin and, indirectly, its regulator, hemojuvelin, in the
      pathogenesis of hemochromatosis but also in anemia of chronic disease. Further
      basic and clinical research is needed to uncover the details of hemojuvelin
      pathophysiology required for potential pharmacological interventions.

PMID- 15875151
TI  - A frequent toll-like receptor (TLR)-2 polymorphism is a risk factor for coronary
      restenosis.
AB  - Restenosis is a major problem for patients undergoing percutaneous transluminal
      coronary angioplasty (PTCA). Inflammatory processes and genetic factors have been
      suggested to be involved in the pathogenesis of both atherosclerosis and
      restenosis. The recently discovered family of Toll-like receptors (TLRs) consists
      of molecules that initiate signaling after host-pathogen interactions. Recently
      it has been shown that the TLRs are involved in the development and progression
      of atherosclerosis by interfering with lipid metabolisms and by mediating
      inflammation. TLR-2 is a key innate immunity receptor for sensing both endogenous
      inflammatory mediators and ligands of several microbial pathogens postulated to
      be involved in atherosclerosis. A frequent single nucleotide polymorphism (SNP)
      for the TLR-2 gene, resulting in a non-functional receptor, has been described.
      By genotyping two independent groups of patients receiving PTCA, followed by
      stent implantation in one group, we found a significantly enhanced frequency of
      the TLR-2 Arg753Gln SNP in patients with restenosis as compared to those without
      restenosis (PTCA: 7.21 versus 2.45%, P = 0.014; PTCA/stent: 6.86 versus 1.53%, P
      = 0.013). In contrast, a common TLR-4 SNP was similarly distributed among the
      patient groups investigated. We furthermore compared the frequency of both SNPs
      in the patients with an age-matched group of individuals without atherosclerosis
      and found a trend towards a lower frequency of the TLR-4 SNP in the
      atherosclerotic group (PTCA: 5.58; PTCA/stent: 3.85 versus 7.14%). We conclude
      that in restenosis a functional TLR-2 is protective and potentially involved in a
      reaction pattern preventing restenosis. Screening for the TLR-2 Arg753Gln SNP may
      be of importance for stratifying a patient's risk and for preventive and
      therapeutic measures.

PMID- 15875152
TI  - [Bioresorbable bone adhesives. Historical perspective and current status].
AB  - Bone adhesives are degraded to non-toxic products and resorbed after fulfilling
      their function in contact with living tissue. There has been a growing interest
      in the use of such adhesives in all fields of medicine in recent years. The wish
      of trauma surgeons and orthopaedic for alternatives to osteosynthesis is
      reflected in the development of a variety of surrogates of biological or
      synthetic origin. Despite a longstanding history of research in this field, a
      clinically applicable alternative in the field of bone gluing has not yet been
      found. This application has consistently failed because these adhesives were not
      tailored to the conditions met within the living organism. The following article
      is meant to provide an overview of the development, the state of the art, and
      today's knowledge of bone adhesives. In addition, it points out the tremendous
      progress in this area, made possible by the joint efforts of basic researchers
      and surgeons. The results of this collaboration show that in the future a
      successful reconstructive surgery using synthetic biomaterials will become
      feasible.

PMID- 15875153
TI  - [Inflammatory diseases of the gall bladder and biliary system. I. Imaging-
      cholelithasis--inflammation of the gall bladder].
AB  - Cholelithiasis is the most common affliction of the gallbladder and biliary
      tract. Including its complications, gallstone disease represents the basis for
      cholecystitis and cholangitis in the majority of cases. Inflammatory diseases of
      the biliary system are divided into acute and chronic forms originating from the
      gallbladder as well as from the biliary tract. Although acute calculous
      cholecystitis is the most common form, gangrenous, and emphysematous inflammation
      of the gallbladder as well as gallbladder empyema are included in this group of
      diseases. In the chronic forms, calculous and acalculous inflammation is also
      differentiated. Recent developments in cross-sectional imaging in sonography,
      computed tomography, and magnetic resonance imaging offer numerous tools for
      depicting the biliary system with high diagnostic accuracy. Invasive imaging
      modalities of the biliary system are mainly used for therapeutic aspects.

PMID- 15875154
TI  - Cellular cholesterol efflux to plasma from moderately hypercholesterolaemic type
      1 diabetic patients is enhanced, and is unaffected by simvastatin treatment.
AB  - AIM/HYPOTHESIS: Cellular cholesterol efflux to plasma is important in reverse
      cholesterol transport and may be affected by simvastatin in type 1 diabetes
      mellitus. METHODS: In 14 moderately hypercholesterolaemic type 1 diabetic and 13
      healthy men we determined plasma (apo)lipoproteins, pre-beta HDL formation,
      cholesteryl ester transfer protein (CETP) activity, phospholipid transfer protein
      (PLTP) activity, cholesterol esterification, cholesteryl ester transfer and the
      capacity of plasma to induce cholesterol efflux out of Fu5AH cells and
      fibroblasts. After diet run-in, diabetic patients were randomly treated with
      simvastatin 10, 20, 40 mg and placebo, once daily each, for 6 weeks in a double
      blind crossover design. RESULTS: Plasma very low density lipid protein (VLDL)+LDL
      cholesterol, LDL cholesterol, HDL phospholipids, apolipoprotein (apo) A-I, apo B,
      CETP activity, PLTP activity, cholesterol esterification, cholesteryl ester
      transfer and the capacity of plasma to induce cholesterol efflux from Fu5AH cells
      and fibroblasts were higher in diabetic patients. Pre-beta HDL formation was
      unaltered. Simvastatin treatment decreased VLDL+LDL cholesterol, LDL cholesterol,
      triglycerides and apo B, CETP activity, cholesterol esterification and
      cholesteryl ester transfer. HDL cholesterol increased and its change was
      correlated with the change in cholesteryl ester transfer. The ability to promote
      cholesterol efflux from Fu5AH cells and fibroblasts did not change after
      simvastatin. CONCLUSIONS/INTERPRETATION: The capacity of plasma from moderately
      hypercholesterolaemic type 1 diabetic patients to induce cholesterol efflux out
      of Fu5AH cells and fibroblasts is enhanced, probably due to higher apo A-I, HDL
      phospholipids and PLTP activity. Simvastatin increases HDL cholesterol in type 1
      diabetic patients via lowering of plasma cholesteryl ester transfer. The HDL
      changes after simvastatin do not increase cellular cholesterol efflux further.

PMID- 15875155
TI  - Increased plasma adiponectin concentrations are associated with microangiopathy
      in type 1 diabetic subjects.
AB  - AIMS/HYPOTHESIS: Insulin resistance is related to an increased risk of diabetic
      retinopathy and nephropathy in type 1 diabetes. Patients with insulin resistance
      and/or macrovascular disease have abnormally low levels of adiponectin. The aim
      of this study was to investigate the relationships between adiponectin and renal
      and retinal diabetic complications in type 1 diabetic patients. METHODS: In this
      6-year prospective follow-up observational study, we evaluated the severity of
      retinopathy at baseline and determined the incident risk of microalbuminuria in
      126 normoalbuminuric patients with type 1 diabetes. Each patient was age- and sex
      matched to two non-diabetic control subjects. RESULTS: Plasma adiponectin
      concentrations were significantly higher in diabetic subjects than in control
      subjects (p < 0.0001). The adiponectin concentration was significantly higher in
      patients with severe diabetic retinopathy than in those without (39.1+/-14.0 vs
      29.0+/-13.0 microg/ml, p = 0.0005). The 18 patients who developed persistent
      microalbuminuria had higher adiponectin concentrations than the other patients
      (35.8+/-14.5 vs 30.6+/-13.7 microg/ml). Increased adiponectin concentrations were
      independently associated with the occurrence of microalbuminuria (p = 0.0158)
      after adjustment for baseline urinary albumin concentration (p = 0.004), sex (p =
      0.0054), blood pressure (NS) and metabolic control (NS).
      CONCLUSIONS/INTERPRETATION: The elevated adiponectin concentrations observed in
      subjects with microvascular disease may indicate an altered regulation of this
      adipocytokine in patients with complications associated with type 1 diabetes.

PMID- 15875156
TI  - [Recommendations for expert assessment of tendon injuries].
AB  - Expert assessment of tendon injuries depends on differences between private and
      public insurance providers in the way preexisting conditions have to be taken
      into account. In most cases degenerative and injury-dependent factors have to be
      balanced. Common tendon injuries such as Achilles and biceps tendon ruptures as
      well as rotator cuff tears are discussed.

PMID- 15875157
TI  - A patient with severe lactic acidosis and rapidly evolving multiple organ
      failure: a case of shoshin beri-beri.

PMID- 15875158
TI  - Meniscal hematoma of the knee joint: a case report.
AB  - We report here an unusual case of medial meniscal hematoma of the knee joint. A
      review of the literature has revealed only one case that was previously reported.
      The authors present the successful decompression of the posterior horn of a
      medial meniscal hematoma through the direct posterior-posterior triangulation
      arthroscopic visualization method. We present here the case report.

PMID- 15875159
TI  - Posteromedial compartment cement extrusion after unicompartmental knee
      arthroplasty treated by arthroscopy: a case report.
AB  - Unicompartmental knee arthroplasty (UKA) with extrusion of cement into the
      posterior compartment of the knee is uncommon. Various problems after a UKA
      procedure, such as aseptic loosening, polyethylene wear and progressive arthritis
      have been reported. This study will report on a patient with extrusion of cement
      fragments into the posteromedial compartment of the knee after a UKA procedure.
      This complication was treated successfully with the direct posterior-posterior
      triangulation arthroscopic visualization method. In cementing the prosthesis, it
      is of paramount importance to take caution to completely remove extruded cement
      remnants in order to prevent this complication during UKA.

PMID- 15875160
TI  - Chondral injury due to migration of a Mitek RapidLoc meniscal repair implant
      after successful meniscal repair: a case report.
AB  - A case of chondral lesion of the medial femoral condyle caused by a bioabsorbable
      Mitek RapidLoc meniscal repair implant is presented. Meniscal repair was quite
      successful, but migration of one of the implanted fixation devices resulted in
      chondral damage, 12 months postoperatively. All orthopaedic surgeons using these
      new devices should be aware of the possibility of chondral damage of the adjacent
      femoral condyles.

PMID- 15875161
TI  - Idiopathic osteonecrosis of the medial tibial plateau.
AB  - Osteonecrosis of the medial tibial plateau is characterized by acute pain on the
      medial aspect of the knee. Progression can lead to articular collapse and
      requires early diagnosis and treatment. We studied seven patients affected of
      idiopathic osteonecrosis of the tibial plateau. The mean age was 62 years and the
      mean follow-up 42 months. We performed roentgenograms in all patients, bone scans
      in three patients and magnetic resonance image (MRI) in five. MRI shows T1
      weighted low-intensity signal and T2-weighted high-intensity signal with a
      surrounding area of intermediate low-intensity signal. An increased focal uptake
      was seen at bone scan. Histological findings showed necrotic bone with empty
      lacunae. Surgical treatment consisted of tibial subchondral drilling in four
      patients-two of them by failure of conservative treatment, and a total knee
      arthroplasty in other two. One patient had a satisfactory evolution with
      conservative treatment. Idiopathic osteonecrosis of the tibial plateau must be
      considered in elderly patients with knee pain over the medial tibial plateau. At
      early stages, decompression with tibial drilling must be considered. This
      procedure allows a prompt and effective relief of symptoms.

PMID- 15875163
TI  - Type IIIB tibial intercondylar eminence fracture associated with a complex knee
      dislocation in a grossly obese adult.
AB  - Avulsion fractures of the intercondylar eminence or tibial spine mostly occur in
      children and adolescents, and are extremely uncommon in adults. A type IIIB
      intercondylar eminence fracture (i.e. completely displaced and rotated tibial
      spine) associated with a complex knee dislocation is an extremely rare
      combination.

PMID- 15875162
TI  - Effect of provider volume on resource utilization for surgical procedures of the
      knee.
AB  - Operating-room time and patient disposition on discharge are important
      determinants of healthcare resource utilization and cost. We examined the
      relation between these determinants and hospital/surgeon volume for anterior
      cruciate ligament (ACL) reconstruction and meniscectomy procedures. Patients
      undergoing ACL reconstruction (18,390 cases) and meniscectomy (123,012 cases)
      were extracted from the State Ambulatory Surgery Databases for the years 1997
      2000. Surgeon and hospital volume were divided into low-, intermediate-, and high
      volume categories. Multivariate logistic regression models were used to estimate
      the adjusted association between surgeon and hospital volume and patient
      discharge status and operating-room time. Patients undergoing ACL reconstruction
      or meniscectomy performed by low-volume surgeons were significantly more likely
      to be non-routinely discharged as compared to high-volume surgeons (adjusted odds
      ratio 3.5, 95% confidence interval 1.7-7.2 for ACL reconstruction; adjusted odds
      ratio 2.0, 95% confidence interval 1.6-2.3 for meniscectomy). The mean operating
      room time for performing ACL reconstruction or meniscectomy was significantly
      higher in low- and intermediate-volume surgeons and hospitals as compared to high
      volume surgeons and hospitals (p < or = 0.001). High-volume providers utilize
      healthcare resources more efficiently. Our findings may help surgeons and
      hospitals in optimizing resource utilization and cost for routinely-performed
      ambulatory surgery procedures.

PMID- 15875164
TI  - The impact of proximal fibula fractures in the prognosis of tibial plateau
      fractures: a novel classification.
AB  - Fifty-five patients who presented with the complaint of tibia plateau fractures
      between January 1998 and November 2001 were retrospectively evaluated. The
      evaluation was based on their treatment modality. Twenty-five conservatively
      treated patients (group 1) and 30 surgically-treated patients (group 2) were
      evaluated. In group 1, seven patients with proximal fibula fractures had lateral
      hamstring tightness. Five out of these seven patients had concomitant lateral
      knee pain. Similarly, nine patients with proximal fibula fractures in group 2 had
      lateral hamstring tightness, and seven patients in the same group suffered from
      lateral knee pain. The patients with no fibula proximal fracture in both groups
      had no hamstring tightness or lateral knee pain. The proximal fibula in the knee
      joint and its anatomical structures are of utmost importance for the anatomical
      integrity of the knee and its normal functions. The fibula has rich anatomical
      relations, some of which are important structures of the knee. These anatomical
      structures and the fibula provide stability of the knee joint and its functions
      as well as being an important mechanical support to the knee joint. Therefore,
      the knee joint will receive the negative effects from the pathologies of the bone
      or soft tissue that may occur in fibula fractures.

PMID- 15875165
TI  - Surgical treatment for persistent complaints following rupture of the fascia of
      the plantaris longus muscle: a case report.
AB  - We report an unusual injury of the plantaris longus muscle with failed
      conservative treatment but successful surgical intervention. A simple surgical
      technique offers a minimally-invasive solution for treating persistent
      complaints.

PMID- 15875167
TI  - Ion-exchange behavior of stannic selenoiodate and stannic selenosilicate:
      analytical application of stannic selenoiodate.
AB  - Two new inorganic ion exchangers, stannic selenoiodate and stannic selenosilicate
      have been synthesized. The ion-exchange capacity of stannic selenoiodate and
      stannic selenosilicate for K+ was found to be 1.84 and 1.23 meq g(-1),
      respectively. pH titration studies reveal monofunctional and bifunctional
      behavior for stannic selenosilicate and stannic selenoiodate, respectively.
      Distribution coefficients of metal ions in dimethylformamide-HCl and formamide
      HCl systems have been determined. Some important and analytically difficult
      quantitative binary and ternary separations, and selective separations of Ag+,
      Sn4+, Zr4+, Co2+, and Ni2+ have been achieved on stannic selenoiodate columns.
      The practical utility of the material has been demonstrated by analyzing the
      metal ion content of electroplating waste.

PMID- 15875166
TI  - Chronic psychosocial stress in tree shrews: effect of the substance P (NK1
      receptor) antagonist L-760735 and clomipramine on endocrine and behavioral
      parameters.
AB  - RATIONALE: Substance P and its preferred receptor, the neurokinin 1 receptor
      (NK(1)R), have been proposed as possible targets for new antidepressant
      therapies, although results of a recently completed phase III trial failed to
      demonstrate that the NK(1)R antagonist MK-869 is more effective than placebo in
      the treatment of depression. METHODS: In the present study, we compared the
      effects of the NK(1)R antagonist L-760735 with the tricyclic antidepressant
      clomipramine on endocrine and behavioral parameters in chronically stressed tree
      shrews. Animals were subjected to a 7-day period of psychosocial stress before
      receiving daily oral administration of L-760735 (10 mg/kg/day) or clomipramine
      (50 mg/kg/day). The psychosocial stress continued throughout the treatment period
      of 21 days. Daily morning urine was collected to measure cortisol and
      norepinephrine levels. All animals were videotaped daily and three types of
      behavior were analyzed. RESULTS: Chronic psychosocial stress resulted in a
      significant increase of urinary cortisol and norepinephrine concentrations.
      Moreover, stressed animals displayed decreased marking behavior and locomotor
      activity, while grooming remained unaffected. Neither treatment with clomipramine
      nor L-760735 was able to normalize the stress-induced elevation of cortisol or
      norepinephrine. On the behavioral parameters, L-760735 had a time-dependent
      restorative influence on marking behavior close to normal levels, without
      affecting locomotor activity. Grooming behavior was significantly increased by
      the 3 weeks of drug treatment. CONCLUSIONS: These results suggest that L-760735
      was able to counteract certain stress-induced behavioral alterations in an animal
      model of depression.

PMID- 15875169
TI  - Out-of-plane trunk movements and trunk muscle activity after a trip during
      walking.
AB  - Tripping during gait occurs frequently. A successful balance recovery implies
      that the forward body rotation is sufficiently reduced. In view of this, adequate
      control of the trunk momentum is important, as the trunk has a high inertia. The
      aim of this study was to establish out-of-plane trunk movements after a trip and
      to determine trunk muscle responses. Ten male volunteers repeatedly walked over a
      platform in which 21 obstacles were hidden. Each subject was tripped over one of
      these obstacles at mid-swing of the left foot in at least five trials.
      Kinematics, dynamics, and muscle activity of the main trunk muscles were
      measured. After a trip, an increase in trunk flexion was observed (peak flexion
      37 degrees). In addition, considerable movements outside the sagittal plane (up
      to 20 degrees) occurred. Already before landing of the blocked foot, the trunk
      forward bending movement was reduced, while trunk torsion and lateral rotation
      were still increasing. Fast responses were seen in both abdominal and back
      muscles, indicating stiffening of the trunk. These muscle responses preceded the
      mechanical trunk disturbances, which implies that these responses were triggered
      by other mechanisms (such as afferent signals from the extremities) rather than a
      simple stretch reflex. A second burst of predominantly trunk muscle extensor
      activity was seen at landing, suggesting specific anticipation of the trunk
      muscles to minimize trunk movements due to landing. In conclusion, despite large
      movements outside the sagittal plane, it appears that trunk muscle responses to
      trips are aspecific and especially aimed at minimizing trunk forward bending.

PMID- 15875168
TI  - Sensorimotor mapping affects movement correction deficits in early Huntington's
      disease.
AB  - Huntington's disease (HD) is associated with early voluntary movement problems
      linked to striatal dysfunction. In pointing movements, HD increases the
      irregularity of the terminal part of movements, suggesting a dysfunction in error
      feedback control. We tested this hypothesis in movements requiring continuous
      feedback control. Patients in the early stages of HD and controls traced as fast
      and accurately as possible circles within a 5-mm annulus on a digitizing tablet
      when visual feedback of the hand and the circle was direct or indirect (through a
      monitor). Patients deviated more often from the annulus and showed larger
      corrections toward the circle than controls when using indirect visual feedback
      but not with direct visual feedback. When velocity requirements were removed,
      patients showed little change in these control problems. These results suggest
      that HD does not affect error feedback control in all movements and that the
      striatal contribution to voluntary movement is sensitive to sensorimotor mapping.

PMID- 15875170
TI  - Compatibility of postural behavior induced by two aspects of visual feedback:
      time delay and scale display.
AB  - Fourteen healthy adults were tested to assess the potential influence on stance
      maintenance of two parts of the visual feedback technique (display scale and time
      delay). The task consisted in their keeping a spot on the screen representing
      their center of pressure, CoP (i.e. successive points of application of the
      ground reaction forces detected by the force platform on which they were
      standing) to a minimum size. The analysis focused on elementary motions computed
      from the complex CoP trajectories, that is the horizontal motion of the center of
      gravity (CoG(h)) and the difference between the CoP and the vertical projection
      of the center of gravity (CoP-CoG(v)). The former is recognized as the main
      variable in postural control, and several interesting features can be extracted
      from the latter. The results indicate that setting a delay and increasing the
      display scale induce substantial reductions in CoP-CoG(v) and CoG(h)
      displacements, respectively. Interestingly, when the two effects are combined,
      these single effects cohabit quite happily. Fractional Brownian motion modeling
      of these trajectories revealed clearly that, in each case, these effects
      originate principally from poor or improved control, respectively. This feature
      confirms that these elementary motions are involved differently in the postural
      system and that study of the complex CoP might not be of great interest. By
      generating opposing but complementary trends, the visual feedback technique
      should thus be perceived as a promising tool for inducing particular postural
      behavior in healthy and disabled individuals.

PMID- 15875171
TI  - Twenty-four hour tolbutamide plasma concentration as a phenotypic measure of
      CYP2C9 activity.

PMID- 15875172
TI  - Hyponatremia in elderly patients treated with desmopressin for nocturia: a review
      of a case series.
AB  - OBJECTIVE: Lately, desmopressin (dDAVP) administered orally has been demonstrated
      to be an effective alternative in the management of nocturia in adults. Although
      the safety profile of dDAVP is well known, much of the experience originates from
      studies in enuretic children and younger adults, and it may not be readily
      extrapolated to elderly patients. In order to identify factors associated with an
      increased risk of hyponatremia in elderly patients treated with dDAVP for
      nocturia, we analysed spontaneous reports accrued from clinical practice in
      Denmark and Sweden. METHOD: Following a selection procedure, the study base
      comprised 15 case reports. From the included reports, information was sought on
      concurrent diseases, concomitant medications and other factors that may
      predispose elderly patients to hyponatremia when treated with desmopressin.
      RESULTS: The median age amongst the cases was 81 years (range 61-93 years) and
      80% were females. For seven of the patients, the hyponatremia occurred during the
      first 3 weeks of treatment. The symptoms presented by the patients led to
      hospitalisation in all but one case. Among patients with information available on
      concomitant medication, half of them were treated with cyclooxygenase inhibitors.
      An excessive fluid intake could only be ascertained in one case; all 15 patients
      eventually recovered. CONCLUSION: In elderly patients treated with dDAVP for
      nocturia, an increased risk of hyponatremia exists in the first weeks of
      treatment. Compared with younger subjects, risk factors other than excessive
      intake of fluid appear to contribute to this adverse drug reaction.

PMID- 15875173
TI  - Preventive treatment of nephrolithiasis with alkali citrate--a critical review.
AB  - Using the keywords "urolithiasis and citrate treatment", "nephrolithaisis and
      citrate treatment", "kidney stones and citrate treatment", a Medline search
      revealed 635 articles published between 1 January 1966 and 1 December 2004. For
      the present analysis, only studies meeting all of the following criteria were
      included: (1) publications in English or German, (2) studies on preventive alkali
      citrate treatment in patients with calcium oxalate, uric acid and infection stone
      disease, (3) clinical studies including at least ten subjects, and (4) treatment
      phases of at least 1 week duration. A total of 43 studies met the inclusion
      criteria and were further subclassified according to intermediate or ultimate
      endpoints as well as to study design. With stone recurrence as the ultimate
      endpoint, 21 uncontrolled studies in almost 1,000 patients demonstrated a
      reduction in stone forming rate by 47-100%. In four randomized controlled trials
      including 227 patients, 53.5% on alkali citrate vs 35% on placebo remained stone
      free after at least 1 year of treatment (P<0.0005). Similar values (66% vs 27.5%
      for alkali citrate vs placebo, P<0.0005) were obtained in 104 patients from two
      randomized trials with dissolution/clearance of residual stones as endpoint.
      Unfortunately, up to 48% of alkali citrate treated patients left the studies
      prematurely, primarily due to adverse effects such as eructation, bloating,
      gaseousness or frank diarrhea.

PMID- 15875174
TI  - Post-pneumonia pyogenic psoas abscess.

PMID- 15875175
TI  - Who is the Silverman of Caffey-Silverman disease?

PMID- 15875176
TI  - Chronic pancreatitis with pancreaticolithiasis and pseudocyst in a 5-year-old boy
      with homozygous SPINK1 mutation.
AB  - We report a 5-year-old boy with a 5-month history of symptoms owing to chronic
      pancreatitis. Abdominal imaging revealed a large pseudocyst in the pancreatic
      tail and concretions in the main pancreatic duct. Successful endoscopic
      papillotomy and stent implantation were performed. Genetic testing showed
      homozygous SPINK1-N34S mutation, which is an established risk factor for chronic
      pancreatitis.

PMID- 15875177
TI  - Non-visualization of sentinel lymph nodes in penile carcinoma.
AB  - PURPOSE: The purpose of this study was to analyse the incidence and cause of non
      visualization of sentinel lymph nodes on preoperative lymphoscintigrams for
      penile cancer and its implications for further management. METHODS: Preoperative
      lymphoscintigraphy was performed after injection of (99m)Tc-labelled nanocolloid
      in 123 clinically node-negative penile carcinoma patients. Anterior dynamic
      lymphoscintigraphy was performed during 20 min immediately after tracer
      injection. Subsequently, 5-min anterior and lateral static images were obtained
      30 min and 2 h post injection. RESULTS: Lymphatic drainage to both groins was
      seen in 98 patients (79%), unilateral drainage in 23 patients (19%) and no
      drainage at all in two patients (2%). Thus, in 27 (11%) of 246 groins, no
      sentinel node was visualized. The amount of administered tracer dose was
      associated with non-visualization (p=0.01). Unilateral drainage was initially
      interpreted as a normal physiological phenomenon. After the occurrence of a
      tumour-positive node in a non-visualized groin, we explore non-visualized groins
      by blue dye mapping and intraoperative palpation. Sentinel nodes were retrieved
      in four out of eight such groins, of which one contained metastasis. CONCLUSION:
      In penile carcinoma patients, preoperative lymphoscintigraphy visualizes a
      sentinel node in 89% of groins. Visualization depends on the administered tracer
      dose. It is worthwhile to explore non-visualized groins. Sentinel nodes can be
      intraoperatively identified in more than half of these cases.

PMID- 15875178
TI  - Positron emission tomography with selected mediastinoscopy compared to routine
      mediastinoscopy offers cost and clinical outcome benefits for pre-operative
      staging of non-small cell lung cancer.
AB  - PURPOSE: (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging
      is an important staging procedure in patients with non-small cell lung cancer
      (NSCLC). We aimed to demonstrate, through a decision tree model and the
      incorporation of real costs of each component, that routine FDG-PET imaging as a
      prelude to curative surgery will reduce requirements for routine mediastinoscopy
      and overall hospital costs. METHODS: A decision tree model comparing routine
      whole-body FDG-PET imaging to routine staging mediastinoscopy was used, with
      baseline variables of sensitivity, specificity and prevalence of non-operable and
      metastatic disease obtained from institutional data and a literature review.
      Costings for hospital admissions for mediastinoscopy and thoracotomy of actual
      patients with NSCLC were determined. The overall and average cost of managing
      patients was then calculated over a range of FDG-PET costs to derive projected
      cost savings to the community. RESULTS: The prevalence of histologically proven
      mediastinal involvement in patients with NSCLC presenting for surgical assessment
      at our institution is 20%, and the prevalence of distant metastatic disease is
      6%. Based on literature review, the pooled sensitivity and specificity of FDG-PET
      for detection of mediastinal spread are 84% and 89% respectively, and for
      mediastinoscopy, 81% and 100%. The average cost of mediastinoscopy for NSCLC in
      our institution is 4,160 AUD, while that of thoracotomy is 15,642 AUD. The cost
      of an FDG-PET scan is estimated to be 1,500 AUD. Using these figures and the
      decision tree model, the average cost saving is 2,128 AUDper patient. CONCLUSION:
      Routine FDG-PET scanning with selective mediastinoscopy will save 2,128 AUD per
      patient and will potentially reduce inappropriate surgery. These cost savings
      remain robust over a wide range of disease prevalence and FDG-PET costs.

PMID- 15875179
TI  - Sentinel node biopsy and selective lymph node clearance--impact on regional
      control and survival in breast cancer and melanoma.

PMID- 15875180
TI  - Losartan renography for the detection of renal artery stenosis: comparison with
      captopril renography and evaluation of dose and timing.
AB  - PURPOSE: Radionuclide renography with angiotensin converting enzyme (ACE)
      inhibition plays an important role in the diagnosis of haemodynamically
      significant renal artery stenosis. Angiotensin receptor antagonists inhibit the
      renin angiotensin system at different levels from ACE inhibitors by selectively
      blocking the binding of angiotensin II to AT1 receptors. The AT1 angiotensin
      receptor antagonist losartan has recently been used clinically in the treatment
      of hypertension. However, the available data on the use of losartan with
      renography for the detection of renovascular hypertension are limited and
      contradictory. The purpose of this prospective study was to compare the
      effectiveness of losartan renography and captopril scintigraphy in revealing
      renal artery stenosis. METHODS: A total of 61 renal units in 32 patients with
      hypertension were studied in two groups based on the losartan dosage (50 mg in
      group A and 100 mg in group B). Group A consisted of 17 patients, in whom 19
      renal units had angiographically proven renal artery stenosis (>or=50%). In group
      B, there were 15 patients, in whom 20 renal arteries were stenotic. All of the
      patients underwent three renographies (baseline, captopril renography and early
      losartan renography). Early losartan renography was performed at 1 h after oral
      losartan administration in both groups. In group B, seven patients underwent
      additional losartan renography (late losartan) performed 3 h after oral losartan
      administration; these patients composed group B1. RESULTS: The sensitivities of
      captopril and losartan studies were 63.2% and 42% in group A, 65% and 65% in
      group B and 55.6% and 66.6% in group B1, respectively. CONCLUSION: From our
      preliminary results, we conclude that losartan is not superior to captopril
      renography for the detection of haemodynamically significant renal artery
      stenosis. However, a high dose (100 mg) of losartan provided higher sensitivity
      than the lower dose (50 mg). Late losartan scintigraphy provided similar
      diagnostic efficacy to early losartan renography.

PMID- 15875181
TI  - Evaluation of a radiolabelled peripheral benzodiazepine receptor ligand in the
      central nervous system inflammation of experimental autoimmune encephalomyelitis:
      a possible probe for imaging multiple sclerosis.
AB  - PURPOSE: Peripheral benzodiazepine receptors (PBRs) are upregulated on
      macrophages and activated microglia, and radioligands for the PBRs can be used to
      detect in vivo neuroinflammatory changes in a variety of neurological insults,
      including multiple sclerosis. Substituted 2-phenyl imidazopyridine-3-acetamides
      with high affinity and selectivity for PBRs have been prepared that are suitable
      for radiolabelling with a number of positron emission tomography and single
      photon emission computed tomography (SPECT) isotopes. In this investigation, the
      newly developed high-affinity PBR ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N
      diethyl)imidazo[1,2-a]pyridine-3-acetamide, or CLINDE, was radiolabelled with
      123I and its biodistribution in the central nervous system (CNS) of rats with
      experimental autoimmune encephalomyelitis (EAE) evaluated. METHODS: EAE was
      induced in male Lewis rats by injection of an emulsion of myelin basic protein
      and incomplete Freund's adjuvant containing Mycobacterium butyricum.
      Biodistribution studies with 123I-CLINDE were undertaken on EAE rats exhibiting
      different clinical disease severity and compared with results in controls.
      Disease severity was confirmed by histopathology in the spinal cord of rats. The
      relationship between inflammatory lesions and PBR ligand binding was investigated
      using ex vivo autoradiography and immunohistochemistry on rats with various
      clinical scores. RESULTS: 123I-CLINDE uptake was enhanced in the CNS of all rats
      exhibiting EAE when compared to controls. Binding reflected the ascending nature
      of EAE inflammation, with lumbar/sacral cord>thoracic cord>cervical cord>medulla.
      The amount of ligand binding also reflected the clinical severity of disease. Ex
      vivo autoradiography and immunohistochemistry revealed a good spatial
      correspondence between radioligand signal and foci of inflammation and in
      particular ED-1+ cells representing macrophages and microglia. CONCLUSION: These
      results demonstrate the ability of 123I-CLINDE to measure in vivo inflammatory
      events represented by increased density of PBRs and suggest that 123I-CLINDE
      warrants further investigation as a potential SPECT marker for imaging of CNS
      inflammation.

PMID- 15875183
TI  - Decreased number of granzyme B+ activated CD8+ cytotoxic T lymphocytes in the
      inflammatory background of HIV-associated Hodgkin's lymphoma.
AB  - This study aimed to assess the differences in the cellular composition of the
      inflammatory reactive background around tumoral cells of classical Hodgkin's
      lymphomas (cHL) inside and outside the HIV settings. This retrospective study
      evaluates the infiltrating T lymphocytes (CD4 and CD8), natural killer cells
      (CD57+ cells), and more especially cytotoxic cells [granzyme B (GrB) and TIA-1+
      cells] in the background of 99 EBV+ cHL. Sections from paraffin-embedded tumor
      samples from nine HIV-infected cHL patients were immunostained, using standard
      immunohistochemical protocols and were compared to a control group of 90 HIV
      noninfected cHL patients. Our clinical and histological data indicate that HIV
      infected cHL patients present a higher frequency of mixed cellularity (MC)
      histological subtypes, more advanced disease stages, a poor response to
      treatment, and a poor overall survival compared to control patients. In controls,
      CD4/CD8 and GrB/TIA-1 ratios were determined as 2:1 and 1:2, respectively. The
      inflammatory infiltrate of HIV-infected patients had a significant reduction of
      CD4+ T lymphocytes (CD4/CD8 ratio 1:23), a decrease in infiltrating GrB+ cells
      (activated cytotoxic cells) and an increase in infiltrating TIA+ T cells (mainly
      nonactivated cytotoxic cells) in these patients (GrB/TIA-1 ratio 1:12). In
      conclusion, this study highlights an important intratumoral loss of CD4+ T cells
      (striking inversion in the CD4/CD8 ratio) and a decrease in intratumoral
      activated cytotoxic T lymphocytes in HIV-associated cHL patients. Further studies
      are required to confirm these results and to determine the role of these findings
      on the antitumoral immune response observed in HIV-associated cHL.

PMID- 15875184
TI  - Molecular epidemiology of follicular lymphoma in Chinese: relationship with bcl
      2/IgH translocation and bcl-6 397G/C polymorphism.
AB  - The relative incidence of follicular lymphoma (FL) compared with diffuse large B
      cell lymphoma (DLCL) is low in Chinese. This may be due to a lower incidence of
      t(14;18)-mediated disease, a rapid transformation of FL to DLCL, or a lower
      incidence of FL-prone genetic polymorphisms (e.g., bcl-6 G397C). Using a
      conventional and long-distance polymerase chain reaction technique, we showed
      that 93% (43/46) of Chinese FL cases are t(14;18) related and are molecularly
      indistinguishable from Caucasian cases. The translocation was uncommonly found in
      Chinese DLCL cases (8/58, 14%). Furthermore, the incidence of bcl-6 hypermutation
      in FL and DLCL cases appeared to be comparable. These data do not suggest a high
      incidence of transformation from FL to DLCL in Chinese. Sequencing study also did
      not show an increased incidence of G397C polymorphism (heterozygote+homozygotes)
      in FL compared to a population with Chinese background or DLCL cases (25+5% vs
      30+4% vs 22+3%). The reasons for the lower incidence of FL in Chinese remain
      unanswered.

PMID- 15875185
TI  - Potent reversal of multidrug resistance by ningalins and its use in drug
      combinations against human colon carcinoma xenograft in nude mice.
AB  - PURPOSE: To evaluate the pharmacological properties and the possible therapeutic
      applications of a series of synthetic marine natural product analogs, ningalins
      (N1-N6), in terms of cytotoxicity, MDR-reversing activity, and enhancement of
      drug combinations with antitumor agents in vitro and in vivo. METHODS: XTT
      assays, [3H]azidopine binding to P-glycoprotein (Pgp), cellular accumulation and
      efflux of labeled drugs were carried out in vitro. Drug combinations using
      combination index, dose-reduction index, and isobologram were performed in vitro
      and enhancement of efficacy in drug combinations against human colon carcinoma
      HCT-116 xenografts were conducted with nude mice. RESULTS: N3 at sub-IC50
      cytotoxic concentration (10 microM) was capable of enhancing vinblastine (VBL)
      cytotoxicity toward human leukemic CCRF-CEM cells about 50,000-fold as measured
      by the decrease of IC50 of VBL. For CCRF-CEM/VBL1000 (1,500-fold resistant to VBL
      and overexpressing Pgp), N3 and N5 enhanced VBL cytotoxicity as much as 6.2
      million-fold and 210,000-fold, respectively. Moreover, N3 and N5 collaterally
      made CCRF-CEM/VBL1000 cells 4,000-fold and 130-fold, respectively, more
      susceptible to VBL than the parent CCRF-CEM cells. In human mammary carcinoma
      cells MX-1/paclitaxel which were 170-fold resistant to taxol and 38-fold
      resistant to VBL, N3 was capable of enhancing VBL effect as much as 6,000-fold.
      Combination therapy on murine P388/doxorubicin (DX) leukemia with DX+N3 or
      taxol+N3 achieved greater efficacy than the therapy with each drug alone.
      Impressively, nude mice, bearing human colon carcinoma HCT-116 cells, treated
      with a suboptimal dosage of taxol in combination with N3, N5 or N6 led to
      shrinkage of established tumor and achieved total tumor remission, while taxol
      alone had no tumor disappearance in this xenograft model. Furthermore, the
      enhancement of antitumor effect by ningalins, at least in parts, are due to
      inhibiting Pgp which was supported by the observation that the ningalins compete
      for [3H]azidopine binding to Pgp, increase the cellular accumulation of VBL or
      taxol, and inhibit drug efflux from the tumor cells. CONCLUSION: The profound
      enhancement of antitumor cytotoxicity of vinblastine and taxol in vitro by
      ningalins may have multiple mechanisms including the MDR-reversing effects. The
      mechanisms for collateral sensitivity by ningalins against sensitive (parent)
      cells are not yet clear. The marked enhancement of therapeutic effect of taxol by
      ningalins against xenograft tumors in nude mice suggests potential applications
      of therapeutic use of ningalins.

PMID- 15875186
TI  - Absence of N-linked glycosylation does not affect plasma membrane localization of
      breast cancer resistance protein (BCRP/ABCG2).
AB  - Breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette (ABC)
      multidrug transporter that confers resistance to various anticancer drugs like
      topotecan and mitoxantrone. To obtain more insight in its cellular functioning,
      we investigated phosphorylation and N-linked glycosylation of BCRP. In the
      epithelial Madin-Darby canine kidney (MDCK) cell line, we did not detect
      phosphorylation of BCRP, in contrast to MRP2, which was phosphorylated. In the
      ovarian carcinoma cell line T8 also no phosphorylated BCRP was detected. As BCRP
      in both lines effectively transports drugs, it appears that phosphorylation of
      BCRP (if it occurs at all) is not needed for drug transport. We further mutated
      the asparagine residues 418, 557 and 596 in three putative N-linked glycosylation
      motifs of BCRP to alanines. Mutant proteins were expressed in CHO9 and MDCKII
      cells by transient transfection and characterized by Western blot and
      immunofluorescence analysis. We found that only BCRP-N596A and a mutant with all
      three asparagines mutated (triple mutant) were not glycosylated anymore,
      indicating that only asparagine 596 is normally glycosylated. The mutation of
      asparagine 596 (or 418) had little effect on the subcellular localization of
      BCRP, indicating that N-linked glycosylation is not essential for routing to the
      plasma membrane. However, BCRP-N557A and the triple mutant were mainly localized
      intracellularly, probably in the endoplasmic reticulum, suggesting that this
      mutation disrupted proper routing of BCRP.

PMID- 15875187
TI  - In vitro sequence-dependent interaction between nedaplatin and paclitaxel in
      human cancer cell lines.
AB  - PURPOSE: To define the most effective combination schedule of paclitaxel and
      nedaplatin, a new platinum derivative, we investigated the in vitro interaction
      between these drugs in AZ-521 and NUGC-4 gastric adenocarcinoma and KSE-1
      esophageal squamous carcinoma cell lines. MATERIALS AND METHODS: Cytotoxic
      activity was determined by the WST-1 assay. Different treatment schedules of the
      two drugs were compared and evaluated for synergism, additivity, or antagonism
      using a quantitative method based on the median-effect principle of Chou and
      Talalay. Cell-cycle perturbation and apoptosis were evaluated by means of flow
      cytometry. RESULTS: Upon 24-h sequential exposure, the sequence paclitaxel
      followed by nedaplatin induced greater than additive effects in all of the cell
      lines, with synergistic interactions in NUGC-4 and KSE-1 cells. By contrast,
      antagonistic effects were observed with the reverse sequence. Simultaneous
      treatment resulted in either a synergistic or antagonistic effect, depending on
      the cell line. Therefore, the sequence paclitaxel followed by nedaplatin appears
      most active, at least in these three cell lines. Flow cytometric analyses at IC50
      indicated that paclitaxel induced G2/M arrest with subsequent induction of
      apoptosis (56%) in the sub-G1 phase. When paclitaxel preceded nedaplatin,
      apoptosis was most prominent (70%) with pronounced G2/M arrest. By contrast, the
      reverse sequence yielded only 28% induction of apoptotic cells, with almost
      identical cell-cycle distribution patterns to those observed with nedaplatin
      alone, indicating that the activity of paclitaxel is abolished by pretreatment
      with nedaplatin. CONCLUSIONS: Our findings suggest that the interaction of
      nedaplatin and paclitaxel is highly schedule dependent and that the sequential
      administration of paclitaxel followed by nedaplatin should be thus incorporated
      into the design of a clinical trial.

PMID- 15875188
TI  - Lack of association of tumor necrosis factor-alpha gene polymorphisms with
      disease susceptibility and severity in Behcet's disease.
AB  - Although it has been reported that the MHC class I molecule, HLA-B51, is a risk
      factor for Behcet's disease (BD), contribution of the tumor necrosis factor (TNF)
      genes, which are located in the vicinity of the HLA-B locus, to the genetic
      susceptibility for BD has yet to be elucidated. The purpose of this study was to
      analyze the effect of TNF-alpha promoter polymorphisms at positions -308, -238
      and -376 on the susceptibility, severity and clinical features of BD. The TNF
      alpha gene sequences from 107 patients with BD and 102 healthy subjects were
      amplified by the polymerase chain reaction. Sequence analysis of the TNF-alpha
      gene locus, which contains promoter polymorphisms at positions -376, -308, and 
      238, was performed with a DNA sequencing kit on automated sequencer. The patients
      were classified according to disease severity and clinical features. Serum TNF
      alpha level in the study groups was measured by sandwich enzyme immunoassay. In
      patients with BD the frequencies of TNF-alpha -308 (19.4% vs 18.4%), -238 (3.7%
      vs 5.9%), and -376 (0.9% vs 2.9%) gene polymorphisms were not found to be
      significantly different from those in healthy subjects. The TNF-alpha gene
      polymorphisms did not show any association with disease severity or clinical
      features. Serum TNF-alpha level was significantly higher in patients with BD than
      in healthy controls (3.10 +/- 1.45 pg/ml vs 2.43 +/- 1.94 pg/ml, P < 0.01). Serum
      TNF-alpha level was not found to be significantly associated with disease
      severity, activity, clinical findings and TNF-alpha genotypes. The results of
      this study suggest that the TNF-alpha gene polymorphisms are unlikely to play an
      important role in the pathogenesis and severity of BD.

PMID- 15875189
TI  - Early effect of nasal salmon calcitonin on the bone marker Crosslaps.
AB  - The aim of this study was to investigate the early effect of nasal salmon
      calcitonin on a bone-resorption marker, "Crosslaps", in postmenopausal
      osteoporotic women. In this randomized, single-blind and placebo-controlled study
      we included 78 postmenopausal women with osteoporosis, between 45 and 65 years of
      age, with at least 5 years duration of menopause. Patients were randomly divided
      into two groups, the treatment and the placebo groups. Patients in the treatment
      group were given 100 IU day(-1) nasal salmon calcitonin, 1,000 mg day(-1)
      elemental calcium, and 400 IU day(-1) vitamin D. Patients in the placebo group
      took only 1,000 mg day(-1) elemental calcium, and 400 IU day(-1) vitamin D. The
      outcome measurements were urinary deoxypyridinoline, serum alkaline phosphatase,
      osteocalcin, and Crosslaps. The treatment group consisted of 39 patients whose
      mean age was 60.4 +/- 6 years and the placebo group included 39 patients with a
      mean age of 60.5 +/- 4.9 years. There was no significant difference between two
      groups in terms of demographic characteristics. The results of bone marker
      measurements were analyzed statistically. Crosslaps levels in the treatment group
      were significantly lower (P < 0.05) than in the placebo group. Other bone marker
      levels at the end of the study were not significantly lower (P > 0.05) than those
      at baseline in both treatment and placebo groups, however. Salmon calcitonin
      affects bone turnover within a few months and bone-resorption markers such as
      Crosslaps can be used to monitor the effect of nasal salmon calcitonin in the
      early phase of treatment for postmenopausal osteoporosis.

PMID- 15875190
TI  - Protoplast transformation and regeneration of transgenic Valencia sweet orange
      plants containing a juice quality-related pectin methylesterase gene.
AB  - Valencia orange [Citrus sinensis (L.) Osbeck] is the leading commercial citrus
      species in the world for processed juice products; however, the presence of
      thermostable pectin methylesterase (TSPME) reduces its juice quality. A long-term
      strategy of this work is to eliminate or greatly reduce TSPME activity in
      Valencia orange. Previous work resulted in the isolation of a putative TSPME
      gene, CsPME4, associated with a thermostable protein fraction of Valencia orange
      juice. To begin research designed to overexpress CsPME4 to verify the
      thermostability of the protein product and/or to downregulate the gene, a sense
      gene cassette containing a gene-specific sequence from a putative TSPME cDNA and
      the enhanced green fluorescent protein (GFP) as a selectable marker was
      constructed (M2.1). In the work reported here, M2.1 plasmid DNA was transformed
      (polyethylene glycol-mediated) into protoplasts isolated from an embryogenic
      suspension culture of Valencia somaclone line B6-68, in an effort to obtain
      transgenic Valencia lines. A vigorous transformed line was identified via GFP
      expression, physically separated from non-transformed tissue, and cultured on
      somatic embryogenesis induction medium. One transgenic proembryo expressing GFP
      was recovered and multiple shoots were regenerated. The recovery of multiple
      transgenic plants was expedited by in vitro grafting. Polymerase chain reaction
      analysis revealed the presence of the PME gene in transgenic plants, and
      subsequent Southern blot analysis confirmed the presence of the eGFP gene. These
      transgenic plants show normal growth and minor morphological variation. The
      thermostability of PME in these plants will be assessed after flowering and fruit
      set. This is the first successful transfer of a target fruit-quality gene by
      protoplast transformation with recovery of transgenic plants in citrus. This
      method of transformation has the advantage over Agrobacterium-mediated
      transformation in that it requires no antibiotic-resistance genes.

PMID- 15875191
TI  - Transgenic Arabidopsis plants expressing Escherichia coli pyrophosphatase display
      both altered carbon partitioning in their source leaves and reduced
      photosynthetic activity.
AB  - The effects of the cytosolic expression of Escherichia coli pyrophosphatase (ppa)
      were investigated in the rosette leaves of transgenic Arabidopsis plants. During
      the daytime, glucose and fructose were found to accumulate at levels that were
      approximately two- to threefold higher in these plants than in the wild type.
      Interestingly, however, neither sucrose nor starch levels showed any distinctive
      build up in transgenic plants except under continuous white light growth
      conditions, during which they accumulated at high levels. Additionally, the
      leaves of transgenic Arabidopsis plants contain two- to threefold higher levels
      of inorganic phosphate (Pi) and two- to sixfold higher levels of uridine
      diphosphate-glucose than wild type plants during the diurnal cycle. In contrast,
      triose phosphate contents in the leaves of E. coli ppa transformants were either
      similar or slightly decreased when compared with wild type leaves. Furthermore,
      the photosynthetic activity of these transgenic plants was found to be reduced by
      20-40% compared to normal levels. These results indicate that induction of ppa
      activity in the cytosol affects carbon partitioning between source and sink
      organs and also that the concomitant increase in Pi caused the accumulation of
      carbon metabolites and reduced photosynthetic activity.

PMID- 15875192
TI  - Tolerance of Bt corn (MON 810) to maize stem borer, Chilo partellus (Lepidoptera:
      Pyralidae).
AB  - Transgenic corn (MON 810), expressing the Bacillus thuringiensis (Bt) protein,
      Cry1Ab, was evaluated under greenhouse conditions for its tolerance to the maize
      stem borer, Chilo partellus. Bt corn (MON 810) provided effective protection
      against the stem borer even under a high level of larval infestation in the
      greenhouse. The observed tolerance is examined and discussed in the light of the
      susceptibility of C. partellus to the Cry1Ab protein in laboratory bioassays. The
      implications of the tissue concentrations of Cry1Ab in MON 810, and baseline
      susceptibility recorded in the current study, for insect-resistance management
      are discussed.

PMID- 15875193
TI  - Influence of high magnetic field strengths and parallel acquisition strategies on
      image quality in cardiac 2D CINE magnetic resonance imaging: comparison of 1.5 T
      vs. 3.0 T.
AB  - The aim of this paper is to examine signal-to-noise ratio (SNR), contrast-to
      noise ratio (CNR) and image quality of cardiac CINE imaging at 1.5 T and 3.0 T.
      Twenty volunteers underwent cardiac magnetic resonance imaging (MRI) examinations
      using a 1.5-T and a 3.0-T scanner. Three different sets of breath-held,
      electrocardiogram-gated (ECG) CINE imaging techniques were employed, including:
      (1) unaccelerated SSFP (steady state free precession), (2) accelerated SSFP
      imaging and (3) gradient-echo-based myocardial tagging. Two-dimensional CINE SSFP
      at 3.0 T revealed an SNR improvement of 103% and a CNR increase of 19% as
      compared to the results obtained at 1.5 T. The SNR reduction in accelerated 2D
      CINE SSFP imaging was larger at 1.5 T (37%) compared to 3.0 T (26%). The mean SNR
      and CNR increase at 3.0 T obtained for the tagging sequence was 88% and 187%,
      respectively. At 3.0 T, the duration of the saturation bands persisted throughout
      the entire cardiac cycle. For comparison, the saturation bands were significantly
      diminished at 1.5 T during end-diastole. For 2D CINE SSFP imaging, no significant
      difference in the left ventricular volumetry and in the overall image quality was
      obtained. For myocardial tagging, image quality was significantly improved at 3.0
      T. The SNR reduction in accelerated SSFP imaging was overcompensated by the
      increase in the baseline SNR at 3.0 T and did not result in any image quality
      degradation. For cardiac tagging techniques, 3.0 T was highly beneficial, which
      holds the promise to improve its diagnostic value.

PMID- 15875194
TI  - Dose optimization of contrast-enhanced carotid MR angiography.
AB  - The purpose of this work was to compare the diagnostic performance of a single
      contrast or a double-contrast dose of carotid contrast-enhanced MR angiography
      (MRA). One-hundred nineteen patients (mean age 65+/-14.4 years) underwent carotid
      contrast-enhanced MRA with a standardized protocol (repetition time/echo 3.73
      ms/1.38 ms, flip-angle 25 degrees, acquisition-time 19 s, voxel size 1.2 x 1.2 x
      0.9 mm3) on a 1.5-T scanner (Sonata, Siemens-Medical-Systems) using a neck phased
      array coil. Contrast agent was administered intravenously at a rate of 3.0 ml/s,
      either as a single dose (n=57; 0.1 mmol/kg body weight) or as a double dose
      (n=62; 0.2 mmol/kg body weight) of meglumine gadoterate (0.5 M/l), followed by 30
      ml saline. Qualitative image analysis was performed on maximum intensity
      projections using a five-point scale. Signal intensities were measured at three
      different vascular levels on both sides to assess the contrast-to-noise ratios
      (CNRs). Image quality was rated as good or excellent in all cases. A double dose
      did not influence the efficacy of carotid enhancement (CNR single dose 69.12+/
      19.8; CNR double dose 70.01+/-20.7; p = 0.81) compared with a single dose. In
      both dose groups the mean CNRs were inversely related to bodyweight, despite
      adjusted contrast volumes (p=0.0005). Double-dose contrast-enhanced carotid MRA
      is not superior to single-dose MRA, as overall diagnostic performance and
      quantitative contrast enhancement are equal. Being more cost-efficient, a single
      dose administration of contrast agent is recommended for MRA of the carotid
      arteries.

PMID- 15875195
TI  - Perfusion abnormalities in congenital and neoplastic pulmonary disease:
      comparison of MR perfusion and multislice CT imaging.
AB  - The aim of this work was to assess magnetic resonance (MR) perfusion patterns of
      chronic, non-embolic pulmonary diseases of congenital and neoplastic origin and
      to compare the findings with results obtained with pulmonary, contrast-enhanced
      multislice computed tomography (CT) imaging to prove that congenital and
      neoplastic pulmonary conditions require MR imaging over the pulmonary perfusion
      cycle to successfully and directly detect changes in lung perfusion patterns.
      Twenty-five patients underwent concurrent CT and MR evaluation of chronic
      pulmonary diseases of congenital (n=15) or neoplastic (n=10) origin. Analysis of
      MR perfusion and contrast-enhanced CT datasets was realized by defining pulmonary
      and vascular regions of interest in corresponding positions. MR perfusion
      calculated time-to-peak enhancement, maximal enhancement and the area under the
      perfusion curve. CT datasets provided pulmonary signal-to-noise ratio
      measurements. Vessel center-lines of bronchial arteries were determined.
      Underlying perfusion type, such as pulmonary arterial or systemic arterial
      supply, as well as regions with significant variations in perfusion were
      determined statistically. Analysis of the pulmonary perfusion pattern detected
      pulmonary arterial supply in 19 patients; six patients showed systemic arterial
      supply. In pulmonary arterial perfusion, MR and multislice CT imaging
      consistently detected the perfusion type and regions with altered perfusion
      patterns. In bronchial arterial supply, MR perfusion and CT imaging showed
      significant perfusion differences. Patients with bronchial arterial supply had
      bronchial arteries ranging from 2.0 to 3.6 mm compared with submillimeter
      diameters in pulmonary arterial perfusion. Dynamic MR imaging of congenital and
      neoplastic pulmonary conditions allowed characterization of the pulmonary
      perfusion type. CT imaging suggested the presence of systemic arterial perfusion
      by visualizing hypertrophied bronchial arteries.

PMID- 15875197
TI  - Gargoyles.

PMID- 15875196
TI  - Central nervous system control of ejaculation.
AB  - An overview is given of the regions in the spinal cord that are active during
      ejaculation. Motoneurons involved are the preganglionic sympathetic motoneurons
      in the upper lumbar spinal cord and the motoneurons in the nucleus of Onuf,
      located in the upper sacral cord. The first group is involved in the so-called
      emission phase of ejaculation, the last group in the expulsion phase. Both groups
      receive afferents from premotor interneurons in the so-called intermediomedial
      cell groups located at about the same level as the motoneurons themselves. A
      concept is put forward in which these premotor cell groups represent the central
      spinal pattern generators for ejaculation, one for the emission phase and one for
      the expulsion phase. Clinical observations in patients suffering from transection
      of the spinal cord indicate that the ejaculation motoneurons as well as their
      spinal central pattern generators are under strong influence of descending
      pathways originating in supraspinal parts of the brain. The various pathways
      possibly involved in ejaculation control are reviewed. Finally, the results of
      the brain activation of a PET-scan study in human males, ejaculating after penile
      stimulation by their female partner are discussed. Especially the ventral
      tegmental area and the cerebellum seem to be activated during ejaculation, while
      the amygdala region is deactivated. Apparently, a general lack of fear is
      necessary for ejaculation to occur.

PMID- 15875198
TI  - Widened clinical spectrum of the Q128P MECP2 mutation in Rett syndrome.
AB  - CASE REPORT: We describe a female patient with Arnold Chiari type I malformation,
      atypical Rett syndrome characterized by postnatal onset microcephaly, stereotypic
      hand movements, ataxia, severe developmental delay, intractable tonic-clonic
      seizures, and a MECP2 mutation with a unique set of clinical findings.
      Implementation of a ketogenic diet resulted in decreased seizure activity and an
      improvement in the patient's degree of social relatedness with her family
      members. DISCUSSION: An early diagnosis of Rett syndrome allows families to
      maximize utilization of existing treatment modalities and seek appropriate
      genetic counseling and prenatal diagnoses. This case also provides further
      evidence for the treatment benefit of ketogenic diets for seizures in patients
      with Rett syndrome.

PMID- 15875199
TI  - Cutaneous lesions in occult spinal dysraphism--correlation with intraspinal
      findings.
AB  - OBJECTS: This study was conducted to investigate the frequency and type of
      cutaneous stigmata in different forms of occult spinal dysraphism (OSD) and their
      correlation to the underlying malformation. METHODS: Fourteen different forms of
      spinal malformations were identified in 358 operated patients with OSD. Most
      frequent findings (isolated or in combinations) were spinal lipoma, split cord
      malformation, pathologic filum terminale, dermal sinus, meningocele manque,
      myelocystocele and caudal regression. Stigmata were present in 86.3% of patients,
      often in various combinations. Using a binary logistic regression analysis,
      significant correlations with distinct malformations were found for subcutaneous
      lipomas, skin tags, vascular nevi, pori, hairy patches, hypertrichosis,
      meningoceles and "cigarette burn" marks. CONCLUSIONS: Cutaneous markers in a high
      percentage accompany spinal malformations. Due to the correlations of different
      stigmata to distinct malformations, they can aid the clinician in further
      diagnostic and therapeutic work.

PMID- 15875200
TI  - Hyperbaric oxygen therapy for the treatment of brain abscess in children.
AB  - INTRODUCTION: The treatment of brain abscess remains a challenging topic usually
      involving a multimodal concept. METHODS: We report our experience with hyperbaric
      oxygen (HBO) therapy in five children presenting with brain abscesses between
      1995 and 2002 at the Department of Neurosurgery, Graz. Mean age was 14.8 (range
      11-17 years). All abscesses were located supratentorially. One child had a single
      abscess and one had multilocated abscesses. Two other patients presented with
      both subdural empyema and brain abscess, one of them showing an epidural empyema
      as well. In another child, the brain abscess was associated with
      meningoencephalitis and subdural empyema. In all of them the underlying condition
      was spread of infection from the paranasal sinuses, except for one, who was
      immunocompromised due to cytotoxic chemotherapy for acute lymphocytic leukaemia.
      RESULTS: One single brain abscess and one of the multiple abscesses were drained.
      All subdural/epidural empyemas were treated surgically. Antibiotics were
      administered intravenously for 13 to 22 days (mean 22 days). All patients
      underwent HBO therapy; the number of treatments ranged from 26 to 45 "dives"
      (mean 30). Treatments were given once daily at 2.2 atmosphere absolutes for 60
      min at 12 m. During the hospital stay all improved their clinical condition, with
      continued regression of abnormalities on magnetic resonance imaging (MRI). In the
      following weeks, other interventions were performed to treat the origin of the
      infections. At 6 months follow-up they were all in good clinical condition,
      either symptom free or with minor residual symptoms. MRI at this time showed no
      evidence of disease in three, a residual dural enhancement in one and a residual
      shrunken collection in the child with multilocated abscesses. No recurrence was
      observed during a mean follow-up of 21 months (range from 7 to 72 months).
      CONCLUSION: HBO therapy in children with brain abscesses seems to be safe and
      effective, even when they are associated with subdural or epidural empyemas. It
      provides a helpful adjuvant tool in the usual multimodal treatment of cerebral
      infections and may reduce the intravenous course of antibiotics and,
      consequently, the duration of hospitalization. Multidisciplinary management is
      recommended to optimize care for these critically ill children.

PMID- 15875201
TI  - Chiari malformation in craniosynostosis.
AB  - INTRODUCTION: Chiari malformation (CM) is a frequent finding in multisutural and
      syndromic craniosynostosis, occurring in 70% of patients with Crouzon's syndrome,
      75% with oxycephaly, 50% with Pfeiffer's syndrome and 100% with the
      Kleeblattschadel deformity. The pathogenesis of this condition and rationale for
      treatment are still controversial. DISCUSSION: Since its first description in
      1972, several factors have been cited to play a role in inducing CM. In the light
      of recent publications, the roles of premature fusion of cranial vault and
      cranial base sutures, of congenital anomalies of the cerebellum and brain stem,
      of raised intracranial pressure, of venous hypertension and of hydrocephalus are
      reviewed. Evaluation and management of CM are also discussed. CONCLUSION: Chiari
      malformation appears to be an acquired and progressive condition that develops in
      the first months of life, because of a disproportion between hindbrain growth and
      an abnormally small posterior fossa, a consequence of the premature fusion of
      lambdoid and cranial base sutures. Venous hypertension caused by stenosis of the
      jugular foramen can also be present in these patients, resulting in intracranial
      hypertension and/or hydrocephalus. Careful MRI evaluation is recommended for the
      forms of craniosynostosis at a high risk of developing hindbrain herniation. The
      selection of posterior cranial vault expansion as the first surgical procedure is
      advocated. In selected cases, treatment of the posterior cranial deformity by
      occipital vault remodelling and treatment of the Chiari-like deformity by
      suboccipital decompression can be carried out using the same surgical procedure.

PMID- 15875202
TI  - Bipolar radiofrequency ablation of liver metastases during laparotomy. First
      clinical experiences with a new multipolar ablation concept.
AB  - BACKGROUND AND OBJECTIVE: Radiofrequency ablation (RFA) is a promising method for
      local treatment of liver malignancies. Currently available systems for
      radiofrequency ablation use monopolar current, which carries the risk of
      uncontrolled electrical current paths, collateral damages and limited
      effectiveness. To overcome this problem, we used a newly developed internally
      cooled bipolar application system in patients with irresectable liver metastases
      undergoing laparotomy. The aim of this study was to clinically evaluate the
      safety, feasibility and effectiveness of this new system with a novel multipolar
      application concept. PATIENTS AND METHODS: Patients with a maximum of five liver
      metastases having a maximum diameter of 5 cm underwent laparotomy and abdominal
      exploration to control resectability. In cases of irresectability, RFA with the
      newly developed bipolar application system was performed. Treatment was carried
      out under ultrasound guidance. Depending on tumour size, shape and location, up
      to three applicators were simultaneously inserted in or closely around the
      tumour, never exceeding a maximum probe distance of 3 cm. In the multipolar
      ablation concept, the current runs alternating between all possible pairs of
      consecutively activated electrodes with up to 15 possible electrode combinations.
      Post-operative follow-up was evaluated by CT or MRI controls 24-48 h after RFA
      and every 3 months. RESULTS: In a total of six patients (four male, two female;
      61-68 years), ten metastases (1.0-5.5 cm) were treated with a total of 14 RF
      applications. In four metastases three probes were used, and in another four and
      two metastases, two and one probes were used, respectively. During a mean
      ablation time of 18.8 min (10-31), a mean energy of 48.8 kJ (12-116) for each
      metastases was applied. No procedure-related complications occurred. The patients
      were released from the hospital between 7 and 12 days post-intervention (median 9
      days). The post-interventional control showed complete tumour ablation in all
      cases. CONCLUSIONS: Bipolar radiofrequency using the novel multipolar ablation
      concept permits a safe and effective therapy for the induction of large volumes
      of coagulation in the local treatment of liver metastases.

PMID- 15875203
TI  - Decreased levels of interleukin-12p40 in the serum of patients with Whipple's
      disease.
AB  - BACKGROUND: An impaired production of interleukin (IL)-12 and T cell interferon
      gamma (IFN-gamma) of in vitro stimulated monocytes has been discussed as a
      pathogenic factor in Whipple's disease (WD). It is unclear whether this defect of
      cellular immunity is translated to the humoral immune system and to serum
      correlates. METHODS: We analyzed the serum of 40 patients with Whipple's disease
      in various degrees of disease activity by sandwich enzyme-linked immunosorbent
      assay for differences in cytokine and cell adhesion molecule concentrations
      compared with age- and sex-matched controls. RESULTS: We observed a highly
      significant reduction of IL-12p40 levels (patients, 0.18+/-0.05 ng/ml (mean+/
      SEM); controls, 3.19+/-0.39 ng/ml; p<0.01) in all stages of disease activity,
      whereas the concentration of IL-12p70 was comparable with controls. Furthermore,
      we observed a slight decrease in tumour necrosis factor alpha (TNF-alpha)
      concentrations in the serum of patients (patients, 6.36+/-0.90 pg/ml; controls,
      10.5+/-1.23 pg/ml; p<0,05). The levels of other cytokines such as IFN-gamma, IL
      2, IL-13 and transforming growth factor beta, as well as soluble cell adhesion
      molecules lymphocyte function-associated antigen 3 and intercellular adhesion
      molecule 1, were not significantly different compared with controls. Levels of
      immunoglobulin G2 (IgG2) measured in the serum of WD patients were below normal
      in 24 of 29 patients and were even below the 95% confidence interval in 10
      patients. CONCLUSION: Our data demonstrate a persistent defect of the cellular
      immune response with decreased serum concentrations of IL-12p40 and TNF-alpha and
      decreased IgG2 levels in a large group of WD patients. These data support as in
      vivo finding the results obtained in previous investigations with stimulated
      monocytes/lymphocytes. The isolated decrease in IL-12p40 may hint at possible
      defects in the IL-12/IFN-gamma promoter system.

PMID- 15875204
TI  - Differential diagnosis of gastrointestinal leiomyoma versus gastrointestinal
      stromal tumor.
AB  - INTRODUCTION: Strategies for the diagnosis of tumors arising in the intestinal
      muscular wall are rapidly evolving. Immunoreactivity for CD117 (KIT) usually
      supports the diagnosis of gastrointestinal stromal tumor (GIST), but a small
      subset of GISTs lacks KIT expression. In these cases the differential diagnosis
      of KIT-negative GIST versus one of their morphological mimics is difficult and
      bears critical implications for therapeutic management. CASE REPORT: Here, we
      report a case of a KIT-negative smooth muscle cell tumor of the colon in a 21
      year-old man with the clinical appearance of GIST. Mutations of the KIT and
      platelet-derived growth factor receptor alpha (PDGFRA) gene could be ruled out.
      No chromosomal imbalances characteristic of GIST were found. However, cytogenetic
      analysis revealed losses at 7q, which has previously been reported in cases of
      uterine leiomyoma. DISCUSSION: We discuss current approaches to the differential
      diagnosis of true gastrointestinal smooth muscle cell tumor versus GIST.

PMID- 15875205
TI  - Hypoplastic thyroid, growth hormone deficiency, corneal opacities, cataract and
      hyperkeratotic skin disease: a possible new ichthyosis syndrome associated with
      endocrinopathies.
AB  - A 56 year old man presented with ichthyosis vulgaris since early childhood,
      clinically characterised by fine scaling of the trunk and hyperkeratotic scales
      on the exterior surfaces of the upper and lower extremities. The patient also
      showed hypothyroidism due to hypoplastic thyroid, cataract, hypercholesterinemia
      with concommitant arcus cornealis and biliary concrements. Renal lithiasis caused
      by calcio-oxalate was additionally present. Endocrinological screening revealed
      growth hormone deficiency in the 1.55 m tall man-(secondary) osteoporosis was
      observed. The clinical symptomatology indicates that this case cannot be
      considered as a subtype of the inherited ichthyosis group, but suggests a new
      syndrome as a separate nosologic entity.

PMID- 15875206
TI  - Pro-inflammatory cytokines upregulate the skin immunoreactivity for NGF, NT-3, NT
      4 and their receptor, p75NTR in vivo: a preliminary report.
AB  - Skin and hair follicles are both source and target of various cytokines and
      neurotrophins (NTs). While several pro-inflammatory cytokines are recognized to
      alter the expression of NTs and their receptors (NTRs), for example, on brain
      cells and fibroblasts in vitro, it is unknown whether this also occurs in normal
      mammalian skin in vivo. As a first step toward exploring this, we studied in
      murine back skin (C57BL/6) whether intradermally injected interleukin-1beta (IL
      1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma)
      altered the cutaneous immunoreactivity patterns of nerve growth factor (NGF),
      brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4
      (NT-4), Trk-A, Trk-B, Trk-C and p75NTR and their receptors (TrkA, TrkB, TrkC,
      p75NTR) on the protein level in situ. By immunohistology, IFNgamma, IL-1beta, and
      TNF-alpha as well as a cocktail of all three cytokines increased NGF
      immunoreactivity (IR) in the proximal outer root sheath and hair matrix of anagen
      VI pelage hair follicles. The cytokine cocktail upregulated NT-3 and NT-4 IR in
      the epidermis, increased NT-4 IR in selected cells of the proximal outer root
      sheath, and also enhanced IR of p75NTR, in the follicular dermal papilla.
      Therefore, this pilot study provides the first preliminary indications that
      proinflammatory cytokines upregulate the cutaneous immunoreactivity of NGF, NT-3,
      NT-4 and their receptor p75NTR in vivo. This raises the question to which extent
      several of the recognized cutaneous effects of IFNgamma, IL-1beta and TNF-alpha
      are mediated indirectly via modulating the expression of selected NTs and/or
      NTRs.

PMID- 15875207
TI  - First trimester diagnosis of partial mole.
AB  - BACKGROUND: Partial mole is one of the two distinctive subtypes of hydatidiform
      mole. It is usually paternally derived triploid conceptions in which embryonal
      development occurs in association with trophoblastic hyperplasia. The definite
      diagnosis is confirmed by pathological and cytogenetic studies. Ultrasound might
      be helpful to diagnose partial mole in the first trimester. CASE: A 25-year-old
      woman, gravida 2, para 0-0-1-0, was initially seen for antenatal care at 6 weeks'
      pregnant. Ultrasound was undertaken at 13 weeks' pregnancy due to her first fetal
      anomaly, which demonstrated partial mole and embryonic death. The serum beta hCG
      was 190,900 mIU/ml. Suction curettage was performed without complication.
      Histopathological study confirmed partial mole and cytogenetic study of the
      placenta revealed an uncommon karyotype, mosaicism of triploid (69,XXX/69,XXY).
      Serum beta hCG was declined and negative at 8 weeks. The patient was well and
      serum beta hCG remained normal throughout 6 months of follow-up. CONCLUSION:
      Although the majority of partial mole pregnancies cannot be detected by routine
      first trimester ultrasound examination, first trimester ultrasound can be helpful
      in some cases, such as this one. If partial mole is sonographically suspected, it
      should be confirmed with histopathology and cytogenetic studies. The management
      is similar to complete mole including prompt evacuation and careful monitoring of
      beta hCG.

PMID- 15875208
TI  - Species identification by means of pyrosequencing the mitochondrial 12S rRNA
      gene.
AB  - The aim of this study was to develop a new method for species identification
      based on the analysis of a very short nucleotide sequence. For this reason, the
      mitochondrial 12S rRNA gene, together with the new method of pyrosequencing, was
      used. The detection of only 20 nucleotides, following the sequencing primer
      within a 149-bp fragment by pyrosequencing, was sufficient to identify the
      biological origin of the samples by alignment with a reference sequence database.
      A case example with a piece of skin is presented, and the question whether this
      piece of skin came from a missing wife or from an animal could be answered.

PMID- 15875209
TI  - The clathrin interacting protein Clint/epsinR in rat testicular germ cells.
AB  - The plasma membrane and the trans-Golgi network (TGN) are major intracellular
      sites for clathrin-mediated membrane budding. Only recently has the clathrin
      interacting protein Clint/epsinR/enthoprotin been identified, which is thought to
      be involved in clathrin-dependent membrane budding from the TGN. Using
      immunocytochemistry, we now report the presence of Clint in the Golgi region of
      spermatocytes and spermatids of the rat testis. Together with subcellular
      fractionation experiments, our data show that, in male germ cells, Clint behaves
      as a peripheral membrane protein that is probably involved in TGN-related vesicle
      budding. Moreover, the immunostaining of the acrosome in round and elongating
      spermatids indicates that Clint operates in membrane traffic between the TGN and
      the acrosome. It may thus be speculated that the protein is involved in the
      biogenesis and shaping of acrosomal membranes.

PMID- 15875210
TI  - The expression of neuregulin and erbB receptors in human skeletal muscle: effects
      of progressive resistance training.
AB  - The neuregulin/erbB-signaling axis contributes to the development and growth of
      multiple mammalian tissues including skeletal muscle. In this study, we sought to
      characterize the native expression of this system in human skeletal muscle and
      test the hypothesis that a program of progressive resistance training (PRT) would
      regulate the expression of neuregulin (NRG) and its cognate receptors. Twelve
      healthy-male subjects underwent 8-weeks of lower-extremity PRT and muscle
      biopsies were performed at baseline and following 1- and 8-weeks of the
      intervention. PRT resulted in significant gains in skeletal muscle strength
      without appreciable changes in fiber size or myosin heavy chain (MHC)
      composition. At baseline, Western Blot analysis demonstrated expression of erbB2,
      erbB3 and erbB4 receptors and multiple NRG isoforms. Following 1- and 8-weeks of
      PRT, no changes erbB2, erbB4 or NRG expression were observed. ErbB3 expression,
      however, was significantly increased at both time points compared to baseline.
      Double labeling of muscle cross-sections revealed increased expression of erbB3
      following PRT was not exclusive to fibers staining positive for MHC IIa. Thus,
      erbB2, erbB3, erbB4 and multiple NRG isoforms are natively expressed in human
      skeletal muscle. Following PRT, a significant increase in erbB3 was observed. The
      ability to detect basal expression and alterations in response to physiologic
      stimuli merit further studies examining the role of this system in skeletal
      muscle.

PMID- 15875211
TI  - Surgical treatment of hepatocellular carcinoma in China: surgical techniques,
      indications, and outcomes.
AB  - BACKGROUND AND AIMS: Surgery remains the most effective treatment for
      hepatocellular carcinoma (HCC). While resection and liver transplantation achieve
      the best outcomes in patients with small HCC, controversy surrounds treatment of
      large HCC, HCC with portal vein tumor thrombus, and HCC with hypersplenism.
      PATIENT/METHODS: From January 1988 to December 2002, 2,102 patients with large
      HCC underwent hepatectomy in our hospital. The traditional resection method was
      used on 959 patients, after which the improved new method was used on 1,143
      patients. Meanwhile, from January 1990 until December 2003, hepatic resection +/-
      thrombectomy has been performed in 438 patients with HCC and portal vein tumor
      thrombus. Among them, 286 patients showed portal vein tumor thrombus located in
      the primary and secondary branch of the main portal vein (group A), and 152
      patients showed portal vein tumor thrombus (PVTT) involved in the main portal
      vein (group B). Additionally, out of 204 HCC patients with cirrhotic
      hypersplenism, 94 patients had hepatectomy and splenectomy, and 100 patients had
      only hepatectomy without hospital death. RESULTS: The 3- and 5-year survival
      after resection of large HCCs (over 5 cm) with improved new method in China was
      between 50.7 and 58.8% and 27.9 and 38.7%, respectively. Tumor recurrence in the
      liver within 1 year after hepatic resection + thrombectomie was detected in 45%
      of group A and in 78.8% in group B. The cumulative 5-year overall survival rates
      were 18.1% for group A and 0% for group B. The 1-, 3-, and 5-year overall
      survival in HCC plus portal vein tumor thrombus (PVTT) was 58.7, 22.7, and 18.1%.
      The hepatectomy/splenectomy group had a 5-year tumor-free survival rate of 37.2%
      and the hepatectomy group alone had 27.2%. CONCLUSION: The new resection methods,
      hepatic resection + thrombectomy and hepatectomy + splenectomy, are very
      effective treatments for large HCC, HCC with portal vein tumor thrombus, and HCC
      with hypersplenism, respectively. Local treatment modalities, e.g. percutaneous
      ethanol injection, cryosurgery, and radiofrequency ablation as well as microwave
      coagulation are used in patients with poor liver function in small and large
      HCCs.

PMID- 15875213
TI  - Age, metabolic control and type of insulin regime influences health-related
      quality of life in children and adolescents with type 1 diabetes mellitus.
AB  - The effects of illness and treatment of diabetes mellitus extend beyond medical
      outcomes. We therefore evaluated health-related quality of life (HRQOL) in
      children (aged 8-12 years) and adolescents (aged 13-16 years) with type 1
      diabetes to compare their results with healthy peers and to identify HRQOL
      determinants. A total of 68 children and adolescents from a tertiary care clinic
      which specialises in the management of diabetes, completed the generic KINDL-R
      questionnaire. This instrument for children and adolescents has six dimensions
      and an additional module assessing condition-related HRQOL. Overall, the HRQOL
      was not different between patients with type 1 diabetes and healthy controls. In
      some areas, children and adolescents with diabetes reported a better HRQOL
      compared to healthy peers: adolescents reported better psychological well-being
      (P < 0.05) and children higher levels of well-being in the school domain (P <
      0.05). In general, children reported a better HRQOL (P < 0.05) than adolescents
      with type 1 diabetes confirming age-related differences in HRQOL in the general
      population. Lower HbA1c (<8%) and intensified insulin therapy (>3 injections/day)
      were associated with a better HRQOL in different domains (P < 0.05). The subscale
      "chronic illness" showed a better HRQOL (P < 0.001) in children and adolescents
      with diabetes compared to age-matched controls with other chronic conditions.
      CONCLUSION: Children and adolescents from a paediatric department specialising in
      diabetes management report good health-related quality of life. Younger age, good
      metabolic control and intensified insulin therapy are associated with a better
      health-related quality of life. Dimensions of health-related quality of life
      appear to play different roles at different ages, emphasising the importance of
      the multidimensional health-related quality of life concept and the value of age
      appropriate self-reports.

PMID- 15875212
TI  - Diethylstilbestrol increases intracellular calcium in lens epithelial cells.
AB  - The effects of diethylstilbestrol (DES) on steady-state intracellular calcium
      concentration ([Ca(2+)](i)) and resting Ca(2+) influx were examined in primary
      cultures of bovine lens epithelial cells using conventional fluorometric
      techniques (Fura-2). At low concentrations (10 microM), DES usually induced
      relatively rapid increases in [Ca(2+)](i) that occurred over an interval of 10-50
      s and that persisted for several minutes in the continued presence of the drug.
      In about 10% of the cells, cyclic oscillations in [Ca(2+)](i) were seen after
      adding 10 microM DES. At higher concentrations (100 microM), the drug induced
      more prolonged increases in [Ca(2+)](i) lasting several minutes. DES did not
      affect Mn(2+) quench determinations of resting Ca(2+) influx, and neither 100
      microM GdCl(3), which blocked resting Ca(2+) influx, nor low [Ca(2+)](o)
      solutions substantially diminished the influence of DES on [Ca(2+)](i).
      Pretreatment of cells with the smooth endoplasmic reticulum Ca(2+) ATPase (SERCA)
      inhibitors cyclopiazonic acid (CPA) or thapsigargin completely abolished the
      effect of 10 microM DES on [Ca(2+)](i), while the IP(3) receptor blocker 2
      aminoethoxydiphenyl borane (2-APB) had no effect. These results indicate that DES
      releases CPA-sensitive stores of intracellular Ca(2+), perhaps by inhibiting
      SERCA-dependent Ca(2+) sequestration.

PMID- 15875215
TI  - Screening for cystic echinococcosis in an endemic region of Peru using portable
      ultrasonography and the enzyme-linked immunoelectrotransfer blot (EITB) assay.
AB  - Cystic echinococcosis (CE) caused by the larval form of Echinococcus granulosus
      is a major public health problem in sheep-raising regions of the World. This
      study compared portable ultrasound with the enzyme-linked immunoelectrotransfer
      blot (EITB) assay as screening methods to estimate the prevalence of human CE in
      a remote village in the Peruvian Andes. Three hundred eighty-nine villagers were
      examined by portable ultrasound and blood samples were drawn by venipuncture.
      Sera were collected and tested for antibodies against CE using an EITB assay.
      Cystic lesions were classified based on their ultrasound morphologic
      characteristics. The prevalence of human CE using portable ultrasound and the
      EITB assay were 4.9% and 2.6%, respectively. Fifty-three percent of subjects with
      CE were EITB positive. Portable ultrasound was well received by the community,
      augmented CE detection and allowed a faster estimate of human infection than the
      EITB assay.

PMID- 15875214
TI  - Evaluation of the role of the endocytic receptor L-SIGN for cytoadhesion of
      Plasmodium falciparum-infected erythrocytes.
AB  - Hepatic cell populations play an important role during the malaria life cycle. L
      SIGN, a homologue of DC-SIGN, mediating leukocyte and pathogen binding, is
      selectively expressed on liver endothelial cells. Here, we present evidence that
      L-SIGN acts as an endocytic cell surface receptor. However, P. falciparum
      infected erythrocytes did not cytoadhere to L-SIGN. Thus, L-SIGN contributes to
      elimination of mannosylated ligands but does not participate in hepatic clearance
      of P. falciparum-infected erythrocytes.

PMID- 15875216
TI  - Adequacy of peritoneal dialysis in children following cardiopulmonary bypass
      surgery.
AB  - Acute renal failure requiring renal replacement therapy can complicate
      cardiopulmonary bypass in children. Peritoneal dialysis has been shown to
      stabilize electrolytes and improve fluid status in these patients. To assess
      dialysis adequacy in this setting, we prospectively measured Kt/V and creatinine
      clearance in five patients (6-839 days of age) requiring renal replacement
      therapy at our institution. Median dialysis creatinine clearance was 74.25
      L/week/1.73m(2) (range 28.28-96.63 L/week/1.73m(2)). Residual renal function
      provided additional solute clearance as total creatinine clearance was 215.97
      L/week/1.73m(2) (range 108.04-323.25 L/week/1.73m(2)). Dialysis Kt/V of >2.1
      (median 4.84 [range 2.12-5.59]) was achieved in all patients. No dialysis
      associated complications were observed. We conclude that peritoneal dialysis is a
      safe, simple method of providing adequate clearance in children who develop acute
      renal failure following exposure to cardiopulmonary bypass.

PMID- 15875217
TI  - Hyperglycemia: its imminent effects on mammalian nephrogenesis.
AB  - A sustained exposure of the mammalian embryo to very high glucose ambience is
      associated with a multitude of congenital birth defects, including those of the
      cardiovascular, CNS, skeletal and urogenital systems during the first 6-8 weeks
      of gestation in humans. These urogenital abnormalities may be associated with
      "caudal regression syndrome" or may occur alone in the form of partial or total
      renal agenesis. Similarly, an increase in the incidence of morphogenetic defects
      is observed in the offspring of streptozotocin-induced diabetic rats and mice,
      and also in non-obese diabetic mice. In certain cases, failure during the growth
      of the lower parts of embryos or newborn mice involving the genitourinary system
      has been observed in animals with severe diabetes. Investigators have utilized
      whole organ culture systems to delineate the mechanisms relevant to
      dysmorphogenesis of the embryonic metanephros. A marked dysmorphogenesis of the
      metanephros is observed upon treatment with a high concentration of D: -glucose.
      Associated with it are changes that include branching dysmorphogenesis of the
      ureteric bud iterations, reduced population of nascent nephrons, decreased
      expression of basement membrane proteoglycans, depletion of ATP stores, and
      fulminant apoptosis of the cells at the interface of mesenchyme and ureteric bud
      epithelium. The latter findings suggest that disruption of epithelial:mesenchymal
      interactions may be the major event responsible for the metanephric
      dysmorphogenesis induced by high glucose ambience.

PMID- 15875218
TI  - Hyperphosphatemia in children receiving peritoneal dialysis--an educational
      program.
AB  - Hyperphosphatemia has been associated with the development of secondary
      hyperparathyroidism, renal osteodystrophy, cardiovascular calcification and
      increased risk of death. Using a one group, pretest-posttest study design, we
      sought to evaluate changes in serum phosphorus, calcium, parathyroid hormone and
      subject knowledge in response to a 3-month educational intervention. Mean serum
      phosphorus levels did not differ significantly between the three evaluation
      periods: pretreatment (5.69 mg/dl), treatment (5.84 mg/dl) and posttreatment
      (6.17 mg/dl). Mean serum calcium, calcium-phosphorus product and PTH values also
      did not differ significantly between the treatment periods. We observed no
      difference between the subject test scores between the two testing periods.
      Calcium-phosphorus product, serum phosphorus and PTH values on average, despite
      the education program, remained outside the K/DOQI target guidelines 44, 56 and
      81% of the time, respectively. The results of this study suggest that an
      aggressive 3-month patient education program targeting dietary phosphorus
      knowledge, phosphate binder name and dosing, and knowledge of medical
      consequences associated with non-compliance had no effect on the serum
      phosphorus, calcium, PTH or phosphate binder need.

PMID- 15875219
TI  - A founder mutation in the CLCNKB gene causes Bartter syndrome type III in Spain.
AB  - The term "Bartter syndrome" encompasses a group of closely related inherited
      tubulopathies characterized by markedly reduced NaCl transport by the distal
      nephron. At present, five different genetic variants have been demonstrated. The
      majority of patients with so-called classic Bartter syndrome carry inactivating
      mutations of the CLCNKB gene encoding the basolateral ClC-Kb chloride channel
      (Bartter syndrome type III). The purpose of this study was to investigate the
      underlying mutation in cases of classic Bartter syndrome followed at our center.
      Ten patients, including two sisters, with clinical and biochemical features of
      classic Bartter syndrome were included in the mutational analysis. They
      originated from different regions of Spain with either Basque or Spanish
      ancestry. There was no history of consanguineous marriage in any of the kindreds.
      The parents and siblings of each patient, as well as a population of 300 healthy
      control adult subjects, were also analyzed. All ten patients were found to be
      homozygous for an identical missense mutation in the CLCNKB gene, substituting a
      threonine for an alanine at codon 204 (A204T) in the putative fifth transmembrane
      domain of the protein. None of the 300 control subjects were homozygous for the
      A204T allele. Overall, the A204T mutation was detected on 2/600 control
      chromosomes. Despite sharing a common mutation, the clinical manifestations of
      the syndrome in the patients varied from lack of symptoms to severe growth
      retardation. Demonstration of a point mutation within the CLCNKB gene as the
      apparently unique cause of Bartter syndrome type III in Spain is highly
      suggestive of a founder effect. Our results also support the lack of correlation
      between genotype and phenotype in this disease.

PMID- 15875220
TI  - Single-dose daily administration of cyclosporin A for refractory nephrotic
      syndrome.

PMID- 15875222
TI  - The upward shift in altitude of pine mistletoe (Viscum album ssp. austriacum) in
      Switzerland--the result of climate warming?
AB  - Pine mistletoe (Viscum album ssp. austriacum) is common in natural Scots pine
      (Pinus sylvestris L.) forests in the alpine Rhone Valley, Switzerland. This semi
      parasite, which is regarded as an indicator species for temperature, increases
      the drought stress on trees and may contribute to the observed pine decline in
      the region. We recorded mistletoes on representative plots of the Swiss National
      Forest Inventory ranging from 450 to 1,550 m a.s.l. We found mistletoe on 37% of
      the trees and on 56% of all plots. Trees infested with mistletoe had a
      significantly higher mortality rate than non-infested trees. We compared the
      current mistletoe occurrence with records from a survey in 1910. The current
      upper limit, 1,250 m, is roughly 200 m above the limit of 1,000-1,100 m found in
      the earlier survey 100 years ago. Applying a spatial model to meteorological data
      we obtained monthly mean temperatures for all sites. In a logistic regression
      mean winter temperature, pine proportion and geographic exposition significantly
      explained mistletoe occurrence. Using mean monthly January and July temperatures
      for 1961-1990, we calculated Skre's plant respiration equivalent (RE) and
      regressed it against elevation to obtain the RE value at the current mistletoe
      elevation limit. We used this RE value and temperature from 1870-1899 in the
      regression and found the past elevation limit to be at 1,060 m, agreeing with the
      1910 survey. For the predicted temperature rise by 2030, the limit for mistletoe
      would increase above 1,600 m altitude.

PMID- 15875221
TI  - Cytochrome P450 3A and 2B6 in the developing kidney: implications for ifosfamide
      nephrotoxicity.
AB  - Repeated administration of agents (e.g., cancer chemotherapy) that can cause drug
      induced nephrotoxicity may lead to acute or chronic renal damage. This will
      adversely affect the health and well-being of children, especially when the
      developing kidney is exposed to toxic agents that may lead to acute glomerular,
      tubular or combined toxicity. We have previously shown that the cancer
      chemotherapeutic ifosfamide (IF) causes serious renal damage substantially more
      in younger children (less than 3 years of age) than among older children. The
      mechanism of the age-related IF-induced renal damage is not known. Our major
      hypothesis is that renal CYP P450 expression and activity are responsible for IF
      metabolism to the nephrotoxic chloroacetaldehyde. Presently, the ontogeny of
      these catalytic enzymes in the kidney is sparsely known. The presence of CYP3A4,
      3A5 and 2B6 was investigated in human fetal, pediatric and adult kidney as was
      the metabolism of IF (both R-IF and S-IF enantiomers) by renal microsomes to 2
      dechloroethylifosfamide (2-DCEIF) and 3-dechloroethylifosfamide (3-DCEIF). Our
      analysis shows that CYP 3A4 and 3A5 are present as early as 8 weeks of gestation.
      IF is metabolized in the kidney to its two enantiomers. This metabolism can be
      inhibited with CYP 3A4/5 and 2B6 specific monoclonal inhibitory antibodies,
      whereby the CYP3A4/5 inhibitory antibody decreased the production of R-3-DCEIF by
      51%, while the inhibitory CYP2B6 antibody decreased the production of S-2-DCEIF
      and S-3-DCEIF by 44 and 43%, respectively, in patient samples. Total renal CYP
      content is approximately six-fold lower than in the liver.

PMID- 15875223
TI  - Accumulation of reactive oxygen species in arbuscular mycorrhizal roots.
AB  - We investigated the accumulation of reactive oxygen species (ROS) in arbuscular
      mycorrhizal (AM) roots from Medicago truncatula, Zea mays and Nicotiana tabacum
      using three independent staining techniques. Colonized root cortical cells and
      the symbiotic fungal partner were observed to be involved in the production of
      ROS. Extraradical hyphae and spores from Glomus intraradices accumulated small
      levels of ROS within their cell wall and produced ROS within the cytoplasm in
      response to stress. Within AM roots, we observed a certain correlation of
      arbuscular senescence and H2O2 accumulation after staining by diaminobenzidine
      (DAB) and a more general accumulation of ROS close to fungal structures when
      using dihydrorhodamine 123 (DHR 123) for staining. According to electron
      microscopical analysis of AM roots from Z. mays after staining by CeCl3,
      intracellular accumulation of H2O2 was observed in the plant cytoplasm close to
      intact and collapsing fungal structures, whereas intercellular H2O2 was located
      on the surface of fungal hyphae. These characteristics of ROS accumulation in AM
      roots suggest similarities to ROS accumulation during the senescence of legume
      root nodules.

PMID- 15875224
TI  - The coinitiator DMABEE induces death by apoptosis and necrosis in human
      monoblastoid cells.
AB  - 4-N,N-Dimethyl amino benzoic acid ethylester (DMABEE), a leachable lipophilic
      component of polymer-based dental-filling materials, has been shown to interact
      with cell membrane phospholipids, such as phosphatidylcholine and
      phosphatidylserine (PS). One marker of cellular death by apoptosis is the change
      in architecture of the plasma membrane involving the translocation of the
      negatively charged PS from the inner to the outer leaflet of the cell membrane.
      We therefore hypothesized that DMABEE has the potential to induce apoptosis. The
      necrosis inducing potential was also investigated. To test our hypothesis human
      monoblastoid U-937 cells were exposed to 10, 20, 40, 80, 120, 160, and 200 microM
      of DMABEE for 24, 48, and 72 h. At the culture end-points apoptotic and necrotic
      cells were detected by flow cytometry. DMABEE enhanced cell death by apoptosis
      and necrosis in U-937 cells in a dose-dependent fashion. The data support our
      hypothesis that DMABEE triggers death-signaling pathways.

PMID- 15875225
TI  - Plasma levels of voriconazole administered via a nasogastric tube to critically
      ill patients.

PMID- 15875226
TI  - Plant and animal microRNAs: similarities and differences.
AB  - Plant and animal microRNAs (miRNAs) are evolutionarily ancient small RNAs,
      approximately 19-24 nucleotides in length, that are generated by cleavage from
      larger highly structured precursor molecules. In both plants and animals, miRNAs
      posttranscriptionally regulate gene expression through interactions with their
      target mRNAs, and these targets are often genes involved with regulating key
      developmental events. Despite these similarities, plant and animal miRNAs exert
      their control in fundamentally different ways. Generally, animal miRNAs repress
      gene expression by mediating translational attenuation through (multiple) miRNA
      binding sites located within the 3' untranslated region of the target gene. In
      contrast, almost all plant miRNAs regulate their targets by directing mRNA
      cleavage at single sites in the coding regions. These and other differences
      suggest that the two systems may have originated independently, possibly as a
      prerequisite to the development of complex body plans.

PMID- 15875227
TI  - Influenza treatment with neuraminidase inhibitors: cost-effectiveness and cost
      utility in healthy adults in the United Kingdom.
AB  - We assessed the cost-effectiveness and cost-utility of treating influenza with
      neuraminidase inhibitors (oseltamivir and zanamivir) from a health care payer's
      and societal perspective in the United Kingdom. A simulation model was developed
      to predict morbidity and mortality due to influenza and its specified
      complications, comparing neuraminidase inhibitors with usual care in an otherwise
      healthy adult population. Robustness of the results was tested by one-way and
      multiway as well as probabilistic sensitivity analyses. Treatment with either
      neuraminidase inhibitor results in reduced morbidity and faster return to normal
      activities. However, oseltamivir dominates zanamivir in cost-utility analysis due
      to its lower costs. Comparing oseltamivir with usual care, the costs are
      pound14.36 per day of normal activity gained and pound5,600 per quality-adjusted
      life-year gained from the healthcare payer perspective. Oseltamivir dominates
      usual care from the societal perspective. Treatment with oseltamivir is a cost
      effective strategy for otherwise healthy adults in the UK from both the
      healthcare payer and societal perspective.

PMID- 15875228
TI  - Obstructive sleep apnea syndrome: effect of respiratory events and arousal on
      pulse wave amplitude measured by photoplethysmography in NREM sleep.
AB  - The objective of the study is to evaluate changes in finger pulse wave amplitude
      (PWA), as measured by photoplethysmography, and heart rate (HR), related to
      obstructive respiratory events and associated arousals during sleep. We analyzed
      1,431 respiratory events in NREM sleep from 12 patients according to (1) the type
      of event (apnea, hypopnea, upper airway resistance episode) and (2) the duration
      of the associated EEG arousal (>10, 3-10, <3 s). Obstructive respiratory events
      provoked a relative bradycardia and vasodilation followed by HR increase and
      vasoconstriction. Relative PWA changes were significantly greater than HR
      changes. These responses differed significantly according to EEG-arousal grades
      (time x arousal interaction, p<0.0001), with longer arousals producing greater
      responses, but not to the type of respiratory event (time x event interaction, p
      = ns). Obstructive respiratory events provoke HR and PWA changes, the magnitude
      seemingly related to the intensity of central nervous activation, with PWA
      changes greater than HR. PWA obtained from a simple pulse oxymeter might be a
      valuable method to evaluate sleep fragmentation in sleep breathing disorders.

PMID- 15875229
TI  - Sleep problems and the risk for sleep disorders in an outpatient veteran
      population.
AB  - We used a self-report questionnaire to identify outpatients with chronic symptoms
      of sleep disorders and/or high pretest probability for sleep apnea as well as for
      restless legs syndrome (RLS), insomnia, and narcolepsy. Surveys were presented to
      patients waiting for an appointment in Veterans Administration (VA) Medical
      Center clinics in Northeast Ohio, USA. Items addressed the frequency of snoring
      behavior; wake time sleepiness or fatigue and history of obesity/hypertension for
      high risk for sleep apnea (Netzer et al. 1999), along with other symptoms, were
      scored as positive vs negative risk for insomnia, narcolepsy, and RLS. Of the
      patients offered the surveys, 886 (59.2%) provided timely responses to the
      questionnaire. Mean age was 62.5 years (range, 19 to 85 years); 95% were males;
      mean body mass index was 29.3 kg/cm(2) (range, 15.1 to 57.5 kg/cm(2)); and mean
      Epworth Sleepiness Scale score was 8.3 (range, 1 to 22) with 4.6% having a score
      >17. Of the respondents, 47.4% met high-risk criteria for sleep apnea, 41.7% for
      insomnia, 19% for restless leg syndrome, and 4.7% for narcolepsy. Twenty-four
      percent reported use of sleeping pills or bedtime alcohol. Drowsy driving >3-4
      days a week or every day was reported in 5.7%. VA primary care patients have high
      prevalence for pretest probability for sleep apnea. This population also reports
      chronic symptoms for other sleep disorders and for drowsy driving.

PMID- 15875230
TI  - Digital recording and analysis of esophageal pressure for patients with
      obstructive sleep apnea-hypopnea syndrome.
AB  - To evaluate sleep-related obstructive breathing events in patients with
      obstructive sleep apnea-hypopnea syndrome (OSAHS), we developed a technique for
      digital recording and analysis of esophageal pressure (Pes) and elucidated the
      Pes parameters. Pes was recorded overnight with a microtip-type pressure
      transducer in 74 patients with OSAHS. Simultaneously, in all patients digital
      polysomnography was recorded. The mean nadir end-apneic Pes swing (Pes Nadir)
      ranged from -20.2 to -147.4 cmH(2)O, with a mean of -53.6+/-2.9 cmH(2)O.
      Correlation of the mean Pes Nadir indicated a linear relationship with the mean
      ratio of maximal Pes swing to apnea duration (r(2)=0.70) and the mean area of the
      Pes (Pes Area) (r(2)=0.82). Significant correlations were noted between the mean
      Pes Nadir and apnea-hypopnea index (AHI, ranging from 7.9 to 109.5 per hour;
      r(2)=0.66), minimum SpO(2) (r(2)=0.60), oxygen desaturation index (ODI) of more
      than 3 (r(2)=0.65), arousal index (r(2)=0.54), and between the mean Pes Area and
      AHI (r(2)=0.63), minimum percutaneous arterial oxygen saturation (SpO(2);
      r(2)=0.57), ODI (r(2)=0.69), and arousal index (r(2)=0.41). Pes parameters were
      found to be significant in the evaluation of the severity of the respiratory
      effort during the sleep-related obstructive breathing events for patients with
      OSAHS.

PMID- 15875231
TI  - Long-term follow-up after primary repair of the anterior cruciate ligament:
      clinical and radiological evaluation 15-23 years postoperatively.
AB  - INTRODUCTION: We have previously reported results after 2-5 and 5-10 years follow
      up of repair of acute anterior cruciate ligament (ACL) ruptures by suturing.
      Reports of results after more than 10 years are rare. MATERIALS AND METHODS: A
      total of 140 patients were operated on in the period 1975-1983 (age range 13-71
      years, median 28 years) by the modified Palmer technique. Only 2 meniscus
      resections and 4 meniscectomies were performed at the primary operation; while 28
      menisci were sutured. At follow-up,12 patients were dead. Eighteen patients (13%)
      underwent repeat operations for secondary instability. Of the remaining 110
      patients, 81 appeared for follow-up. RESULTS: Only 6 secondary meniscus
      resections were performed, all in the group of 18 patients operated on again for
      instability. No secondary meniscus surgery was performed on the 81 patients who
      appeared for follow-up. The median Lysholm score was 88, and 58 of the 81
      patients (71%) classified their total knee function as good or excellent. By KT
      1000 testing, 33 (41%) patients had less than 3 mm anterior instability, 29 (36%)
      had 3-5 mm instability, and 17 (21%) had more than 5 mm. With 18 patients from
      the total of 128 living patients re-operated for instability, we estimate the
      rate of total failure of stability as 27%. Radiological osteoarthritis grade C
      was present in 8 operated and 2 control knees, while only 1 operated knee
      revealed osteoarthritis grade D. Thirty-four operated and 20 control knees had
      grade B. Osteoarthritis was correlated to more advanced age at injury, while
      correlation to function could not be proven. Radiographs were obtained of 61
      patients at follow-up. CONCLUSIONS: Some 50% of patients had stable or slightly
      unstable knees, and 40% good or excellent function according to the Lysholm
      score. Re-operation for instability was more frequent in younger patients, while
      ostearthritis was more frequent in older patients. The rate of meniscus resection
      or extirpation was low. Open repair by suture is no longer recommended. Further
      research is indicated on the possible use of refixation of the ruptured ACL by
      arthroscopy.

PMID- 15875232
TI  - Altered signal intensity in the posterior horn of the medial meniscus: an MR
      finding of questionable significance.
AB  - INTRODUCTION: MR imaging has emerged as an important modality in the non-invasive
      evaluation of osseous and soft-tissue structures in the post-traumatic knee.
      However, it is sometimes impossible to determine with confidence if a focus of
      high signal intensity in the meniscus is confined to the substance of the
      meniscus or if it extends to involve the joint surface. This is a critical
      differentiation because the latter represents meniscal tears that can be found
      and treated arthroscopically, whereas the former represents degeneration,
      intrasubstance tears or perhaps normal variants that are not amenable to
      arthroscopic intervention. The aim of this study was to investigate the
      occurrence of such borderline findings in relation to the posterior horn of the
      medial meniscus and to correlate the arthroscopic results. MATERIALS AND METHODS:
      Sixty-four patients with suspected post-traumatic internal derangements of the
      knee who underwent MR imaging prior to arthroscopy were evaluated
      retrospectively. There were 48 men and 16 women. Their mean age was 28.2 years.
      RESULTS: Tears of the posterior horn of the medial meniscus were diagnosed
      unequivocally (grade 3 signal) in 18 patients and equivocally (grade 2/3 signal)
      in 10 patients. Arthroscopic correlation revealed 16 tears (89%) in the
      unequivocal group and only 1 tear (10%) in the equivocal group. CONCLUSION: A
      meniscal tear is unlikely when MR shows a focus of high signal intensity in the
      posterior horn of the medial meniscus that does not unequivocally extend to
      involve the inferior or superior joint surface. An appropriate trial of
      conservative treatment is recommended in such questionable cases. MR is a useful
      diagnostic tool-however, it should be used selectively, and in conjunction with
      history and clinical examination in evaluating internal derangements of the knee.

PMID- 15875233
TI  - Spontaneous rupture of extensor pollicis longus tendon with tophaceous gout
      infiltration.
AB  - INTRODUCTION: Spontaneous rupture of the extensor pollicis longus (EPL) tendon
      has been reported in the literature. Various mechanisms have been proposed to
      account for this problem, but gouty infiltration is a rare mechanism. Here we
      report a patient with a long-standing history of gout who presented with sudden
      loss of interphalangeal extension of the left thumb. Spontaneous rupture of the
      EPL tendon caused by gout was discovered. MATERIALS AND METHODS: The successful
      treatment done involved surgical exploration and extensor indicis proprius tendon
      transfer. Postoperative thumb spica immobilization for 6 weeks was applied.
      RESULTS: Pathology disclosed urate crystals deposited within the ruptured EPL
      tendon. The functional recovery is satisfactory at the 1-year follow-up.
      CONCLUSION: Spontaneous rupture of the EPL tendon caused by gout is rare.
      Successful treatment was done with surgical management. Life-long medical follow
      up to prevent a repeated acute attack can lower the risk of a large amount of
      tophaceous gout infiltration in tendons and may possibly prevent acute
      spontaneous tendon rupture.

PMID- 15875234
TI  - P-QOL: a validated questionnaire to assess the symptoms and quality of life of
      women with urogenital prolapse.
AB  - To develop a simple, valid, reliable questionnaire to assess the severity of
      symptoms and their impact on the quality of life in women with urogenital
      prolapse. Women recruited from gynaecology outpatient clinics were asked to
      complete a prolapse quality of life questionnaire (P-QOL) before their hospital
      visit. At the time of the visit, they were examined supine using the
      International Continence Society (ICS) prolapse score (POP-Q). A second P-QOL was
      posted and completed by patients 2 weeks later. The validity was assessed by
      measuring levels of missing data, comparing symptom scores between affected and
      asymptomatic women and comparing symptom scores with objective prolapse stages.
      The internal reliability was assessed by measuring the Cronbach alpha
      coefficient; 155 symptomatic and 80 asymptomatic women were studied. Severity
      according to P-QOL strongly correlated with the vaginal examination findings (p <
      0.01, rho > 0.5). The total scores for each P-QOL domain were significantly
      different between symptomatic and asymptomatic women (p < 0.001). All items
      achieved a Cronbach alpha greater than 0.80 showing good inter-rater reliability.
      The test-retest reliability confirmed a highly significant correlation between
      the total scores for each domain. A P-QOL questionnaire for English-speaking
      patients has been developed which is reliable and valid.

PMID- 15875235
TI  - Surgical reinforcement of support for the vagina in pelvic organ prolapse:
      concurrent iliococcygeus fascia colpopexy (Inmon technique).
AB  - To reinforce the support of the vagina, concurrent use of iliococcygeus fascia
      colpopexy with the McCall culdeplasty was scheduled for primary uterine prolapse.
      Forty-five women with primary uterine prolapse without stress urinary
      incontinence were treated by McCall culdeplasty alone or McCall culdeplasty plus
      iliococcygeus fascia colpopexy for suspension of the upper portion of the vagina.
      Recurrence of vaginal support defects were carefully followed for 15-50 months.
      Additional iliococcygeus fascia colpopexy did not change with the axis of the
      vagina obtained by McCall culdeplasty, although it prolonged total operation time
      by 32 min and increased blood loss by 94 ml. Two cases (8.3%) had postoperative
      vaginal defects in the group undergoing combined procedures and seven recurrent
      cases (33.3%) were observed in the group undergoing McCall culdeplasty alone. The
      durability of the combined procedures was superior to that of the modified McCall
      culdeplasty alone by Kaplan-Meier analysis. These results suggest that
      iliococcygeus fascia colpopexy is reasonably safe and strengthens not only the
      attachment of the upper part of the vagina but also that of the anterolateral
      vaginal wall.

PMID- 15875236
TI  - Predictive value of prolapse symptoms: a large database study.
AB  - We sought to describe the relationship between patient symptoms and pelvic organ
      prolapse (POP) and report the sensitivity, specificity, and positive and negative
      predictive value of these POP symptoms. Two urologists and four urogynecologists
      developed a standardized pelvic floor questionnaire based on face validation for
      use at three female pelvic floor disorder clinics. Specific questions related to
      prolapse included questions on urinary splinting, digital assistance for
      defecation, and a bulge per vagina. Prolapse was assessed with the standardized
      Pelvic Organ Prolapse Quantitative (POP-Q) terminology. The analysis included
      1912 women. Urinary splinting was uncommon (< 10%) when Ba < 0, but ranged
      between 23 and 36% for stage III and IV Ba prolapse. Digital assistance was
      equally common in stage II Bp prolapse (21-38%) and stage III-IV Bp prolapse (26
      29%). Only 6-11% of women with stage 0 or I POP reported symptoms of bulge, but
      with stage II it increased to 77%. Urinary splinting is 97% specific for anterior
      prolapse. The report of a bulge has an 81% positive predictive value and a 76%
      negative predictive value. Very few patients without anterior prolapse will
      report urinary splinting. Digital assistance for fecal evacuation is no more
      common with massive posterior prolapse than with moderate posterior prolapse.
      Patient report of a bulge is a valuable screening tool for POP and should prompt
      a careful exam.

PMID- 15875237
TI  - Complications associated with the tension-free vaginal tape procedure: the Korean
      experience.
AB  - The object was to assess the incidence of complications in patients who had
      undergone the tension-free vaginal tape procedure and their management. A total
      of 274 women 28-80 years old (mean: 55.1) with a minimum follow-up of 6 months
      were included in the study. Follow-up evaluation included questionnaire
      assessment, physical examination with a stress test, uroflowmetry and postvoid
      residual urine measurement. Bladder perforations were noted in 13 (4.7%). Thirty
      eight patients (13.9%) had postvoid residual urine volume >100 ml twice
      consecutively or failed to void. Twenty-three women had resolution of their
      voiding dysfunction with intermittent catheterization. Fourteen patients
      underwent urethral dilatation and four subsequently underwent a release and/or
      cutting of the tape. Fifty-seven patients (20.8%) had other voiding problems, but
      a normal voiding pattern was achieved spontaneously in 34. Fourteen women have
      shown resolution of their voiding symptoms after urethral dilatation. The present
      study demonstrates that the tension-free vaginal tape procedure is a safe
      technique for the treatment of female urinary incontinence. In addition, our
      findings suggest that there may be a role for urethral dilatation in the
      management of voiding difficulty associated with the procedure.

PMID- 15875238
TI  - Use of three-dimensional ultrasound scan to assess the clinical importance of
      midurethral placement of the tension-free vaginal tape (TVT) for treatment of
      incontinence.
AB  - The aim of the study is to illustrate that the midurethral positioning of the
      tension-free vaginal tape (TVT) may not be necessary to achieve continence. Our
      secondary aim is to highlight that a fair number of successfully performed TVT
      procedures do not result in midurethral position of the tape. A review of 31
      women who underwent TVT operations and consecutively returned for their follow-up
      visits from July 2003 to November 2003 was conducted. Their TVT procedures were
      performed between March 2000 and August 2003. Transperineal three-dimensional
      ultrasound was used to identify and obtain objective measurements of the position
      of the TVT tape relative to the urethra. Any patients with significant coexisting
      vault or uterovaginal prolapse were surgically corrected at the same time. Their
      stress urinary incontinence was objectively diagnosed by performing urodynamic
      studies (dual-channel subtraction cystometry, erect stress test) in the
      outpatient urogynaecology clinic. Postoperatively, patients were reviewed at 1
      month and then at 6 months followed by annual reviews subsequently. All women
      were reassessed at the 6-month follow-up visit with a filling and voiding
      cystometry to detect recurrent genuine stress incontinence and detrusor
      instability. Any woman complaining of stress urinary incontinence after that was
      reassessed with urodynamic studies as mentioned above. The majority of women
      (67.7%, 21 women) had the TVT tape located in the middle one-third of the
      urethra; 9.7% (3 women) and 22.6% (7 women) of women had the TVT tape situated in
      the proximal and distal one-third of the urethra, respectively. Despite this, all
      31 women remained continent at their postoperative follow-up visits. The
      midurethral position of the TVT tape may not be essential in restoring
      continence. The TVT tape once inserted may not always rest in the midurethral
      position as described.

PMID- 15875239
TI  - Effectiveness of the McCall culdeplasty in maintaining support after vaginal
      hysterectomy.
AB  - The aim of this study was to evaluate the effectiveness of a McCall culdeplasty
      in maintaining support of the post-hysterectomy vaginal cuff in women undergoing
      surgery for uterine prolapse. A retrospective chart review was performed on all
      patients who had a vaginal hysterectomy and McCall culdeplasty for uterine
      prolapse without prolapse of the posterior vaginal fornix. Patients were examined
      pre- and postoperatively using the International Continence Society (ICS) staging
      system. Data were analyzed using repeated measures analysis of variance (ANOVA)
      for correlation between preoperative point D and the two postoperative point C
      measurements. Of the 43 patients studied, 39 (90%) had stage 0 prolapse and 3
      (7%) had stage I prolapse of the vaginal cuff 1 year postoperatively. In patients
      who have hysterectomies for uterine prolapse with good support of the posterior
      vaginal fornix, the McCall culdeplasty is a highly successful procedure in
      maintaining proper anatomic support of the vaginal cuff.

PMID- 15875240
TI  - Randomized comparison of the suprapubic arc sling procedure vs tension-free
      vaginal taping for stress incontinent women.
AB  - The purpose of this study was to compare the surgical outcome and attendant
      complications of the suprapubic arc (SPARC) sling and tension-free vaginal tape
      (TVT) procedures. Sixty-two women with genuine stress incontinence (GSI) alone or
      combined with pelvic prolapse less than International Continence Society (ICS)
      stage II were randomly allocated to either SPARC or TVT groups. A routine
      suprapubic ultrasonography was performed for all patients 1 day after the anti
      incontinence operation. A comparison of the peri- and postoperative results
      comprising surgical outcomes and complications revealed no significant
      differences between the two groups. Although the difference in the rates of
      bladder injury was not statistically significant (SPARC 12.9 vs TVT 0.0%, p =
      0.112), it was clinically significant. Routine suprapubic ultrasonography
      revealed eight subjects had retropubic hematomas greater than 5 cm. The cure rate
      for SPARC was not significantly different from TVT (80.7 vs 87.1%, p = 0.706). We
      concluded that the SPARC sling and TVT procedures proved to be equally effective.
      Subsequent suprapubic ultrasonography, in particular for the symptomatic
      patients, was found to be of clinical merit.

PMID- 15875241
TI  - Updated recommendations on ultrasonography in urogynecology.
AB  - Ultrasound is a supplementary, indispensable diagnostic procedure in
      urogynecology; perineal, introital, and endoanal ultrasound are the most
      recommended techniques. The position and mobility of the bladder neck can be
      demonstrated. In patients undergoing diagnostic work-up for urge symptoms,
      ultrasound occasionally demonstrates urethral diverticula, leiomyomas, and cysts
      in the vaginal wall. These findings will lead to further diagnostic assessment.
      The same applies to the demonstration of bladder diverticula, foreign bodies in
      the bladder, and bullous edema. With endoanal ultrasound, different parts of the
      sphincter ani muscle can be evaluated. Recommendations for the standardized use
      of urogenital ultrasound are given.

PMID- 15875242
TI  - Development of vesical calculi following tension-free vaginal tape procedure.
AB  - We present a case of a bladder stone that had formed around the intravesical
      portion of tension-free vaginal tape (TVT) material following unnoticed bladder
      perforation during the procedure. Endoscopic lithotripsy of the bladder calculi
      was performed and the TVT sling material was removed by an endoscopic approach.
      High clinical suspicion of bladder complications is necessary when evaluating
      patients presenting with urinary symptoms after a TVT procedure.

PMID- 15875243
TI  - Removal of a missed polypropylene tape by a combined transurethral and
      transabdominal endoscopic approach.
AB  - Surgical intervention for bladder perforation caused by application of a
      transvaginally placed polypropylene tape is rare. Open as well as endoscopic
      procedures for removal from the bladder have been described earlier. In this case
      report we describe the removal of an intravesical polypropylene tape by a
      combined transurethral and transabdominal endoscopic approach 3 months after the
      initial surgical procedure.

PMID- 15875244
TI  - Chemically Substituted Apatites. Proceedings from the 7th World Biomaterials
      Congress, Sydney, Australia, May, 2004.

PMID- 15875246
TI  - Influence of ferrous iron incorporation on the structure of hydroxyapatite.
AB  - Iron is a vital element of cellular function within the body. High concentrations
      of iron can be found in the kidneys and the circulatory system. In bones and
      teeth it is present as a trace element. The use of iron-based compounds in
      combination with hydroxyapatite offers a new alternative for prosthetic devices.
      This work investigates the synthesis and processing of iron containing apatites
      as a possible new type of ceramic for biomedical devices. Stoichiometric and
      calcium deficient iron containing apatites were synthesized by a wet chemical
      reaction with di-ammonium-hydrogen-phosphate, calcium nitrate and a ferrous iron
      nitrate solution. A secondary phase of tri-calcium-phosphate (TCP) was observed
      after heat treatment of iron containing, calcium deficient, hydroxyapatite. The
      apatite structure was maintained after heat treatment of stoichiometric apatite,
      synthesized in the presence of iron. Sintering in air produced oxidation of Fe2+
      to Fe3+, resulting in the formation of hematite as a secondary phase. The
      introduction of iron into the synthesis of hydroxyapatite causes: (i) an increase
      of the a-lattice parameter after synthesis and heat treatment in air; (ii) an
      increase in the c-lattice parameter after sintering in air.

PMID- 15875245
TI  - Fluorapatite-mullite glass sputter coated Ti6Al4V for biomedical applications.
AB  - A number of bioactive ceramics have been researched since the development of
      Bioglass in the 1970's. Fluorapatite mullite has been developed from the dental
      glass-ceramics used for more general hard tissue replacement. Being brittle in
      nature, glass-ceramics are currently used mainly as coatings. This paper shows
      that fluorapatite glass LG112 can be used as a sputtered glass coating on
      roughened surfaces of Ti6Al4V for possible future use for medical implants. An
      AFM was used to measure the roughness of the surface before and after coating to
      determine the change in the topography due to the coating process as this greatly
      affects cell attachment. The sputter coating partially filled in the artificially
      roughened surface, changing the prepared topography. Osteoblasts have been
      successfully grown on the surface of these coatings, showing biocompatibility
      with bone tissue and therefore potential use in hard tissue repair.

PMID- 15875247
TI  - Studies on calcium deficient apatites structure by means of MAS-NMR spectroscopy.
AB  - The development of synthetic apatites that replicate the features and properties
      of the contained in natural tissues will help to diminish the misfit between
      artificial implants and natural hostesses but the structure of these compounds is
      still under discussion. The variability in Ca/P ratio of calcium deficient
      apatites has been explained through different models: surface adsorption, lattice
      substitution and intercrystalline mixtures of hydroxyapatite and octacalcium
      phosphate. This work investigates which of the models mentioned suits better in a
      range of samples. Hydroxyapatites obtained by precipitation, by hydrolysis of
      dicalcium phosphate and calcined samples with Ca/P ratio between 1.50 and 1.77
      and specific surface area between 7 and 108 m2/g have been analysed. OCP and
      surface adsorption models suit better for great SSA particles and low Ca/P ratio
      while for smaller SSA particles the lattice substitution model is more accurate.
      SSA also plays the main role when the capacity to absorb substances is studied
      though their chemistry can not be explained solely in terms of surface
      reactivity.

PMID- 15875248
TI  - Dissolution and mineralization of sintered and thermally sprayed hydroxy
      fluoroapatites.
AB  - Hydroxyapatites are commonly used as bone cement, coatings on implants for dental
      and orthopaedic applications, but also as middle ear implants. These applications
      all require a different tissue healing response that can be attained by different
      manufacturing processes or by chemically modifying the composition. During
      implantation apatites undergo a process of dissolution and mineralization. The
      degree of dissolution is dependent upon the manufacturing process & is higher for
      thermally sprayed implant materials. This allows them to integrate to the natural
      bone. This study tests the dissolution and mineralization of fluoride containing
      hydroxyapatites through immersion in simulated body fluid. It shows that
      mineralization occurs more readily in hydroxyapatites than fluorapatites because
      of their higher dissolution rate. Mineralization was detected most readily by
      image analysis using scanning electron microscopy than by weight changes using a
      microbalance. Microscopy allowed small heterogeneous precipitates to be observed
      during the initial stages of mineralization.

PMID- 15875249
TI  - Ion exchanges in apatites for biomedical application.
AB  - The modification of the composition of apatite materials can be made by several
      processes corresponding to ion exchange reactions which can conveniently be
      adapted to current coatings and ceramics and are an alternative to setting up of
      new synthesis methods. In addition to high temperature thermal treatments, which
      can partly or almost totally replace the monovalent OH- anion of stoichiometric
      hydroxyapatite by any halogen ion or carbonate, aqueous processes corresponding
      to dissolution-reprecipitation reactions have also been proposed and used.
      However, the most interesting possibilities are provided by aqueous ion exchange
      reactions involving nanocrystalline apatites. These apatites are characterised by
      the existence on the crystal surface of a hydrated layer of loosely bound mineral
      ions which can be easily exchanged in solution. This layer offers a possibility
      to trap mineral ions and possibly active molecules which can modify the apatite
      properties. Such processes are involved in mineralised tissues and could be used
      in biomaterials for the release of active mineral species.

PMID- 15875250
TI  - A new way of incorporating silicon in hydroxyapatite (Si-HA) as thin films.
AB  - Bioactive silicon-containing hydroxyapatite (Si-HA) thin films that can be used
      as coatings for bone tissue replacement have been developed. A magnetron co
      sputtering technique was used to deposit Si-HA films up to 700 nm thick on
      titanium substrates, with a silicon level up to 1.2 wt%. X-ray diffraction
      demonstrated that annealing transformed the as-deposited Si-HA films which were
      amorphous, into a crystalline HA structure. A human osteoblast-like (HOB) cell
      model was used to determine the biocompatibility of these films. HOB cells were
      seen to attach and grow well on the Si-HA films, and the metabolic activity of
      HOB cells on these films was observed to increase with culture time. Furthermore,
      mineralisation of the cell layers was observed after 8 weeks of culture. Based on
      the present findings, Si-HA of different film compositions demonstrate bioactive
      properties in-vitro, and indicate the potential as biocoatings for a wide variety
      of medical implants including load-bearing applications such as the femoral stem
      of hip replacement implants.

PMID- 15875251
TI  - Synthesis and structure of cerium-substituted hydroxyapatite.
AB  - The aim of this study was to explore the effect of cerium ions on the formation
      and structure of hydroxyapatite (HAP). All particles, prepared by hydrothermal
      method, were synthesized at varied X(Ce) = Ce/(Ca + Ce) (from 0 to 10%) with the
      atomic ratio (Ce + Ca)/P fixed at 1.67. Their morphology, composition and crystal
      structure were characterized by TEM, EPMA, XRD and FTIR. The results showed that
      in this composition range the apatite structure is maintained, Ce3+ ions could
      enter the crystal lattice of apatite and substitute Ca2+ ions. The doping of Ce3+
      ions resulted in the decrease of the crystallite size with increase in X(Ce). The
      HAP particles without doping were short rods having a diameter from 10 to 20 nm
      and a length from 30 to 50 nm. They grew into long needles upon increasing X(Ce).

PMID- 15875252
TI  - Alkali ion substituted calcium phosphate cement formation from mechanically
      activated reactants.
AB  - Potassium and sodium containing nanoapatite cements were produced from
      Ca2KNa(PO4)2 by prolonged high energy ball milling of the compound for up to 24
      h. This mechanical treatment resulted in the decrease of the crystal size and a
      partial amorphisation of the cement reactant as shown by X-ray diffraction
      analysis and the appearance of strong exothermic peaks in differential scanning
      calorimetry measurements. The pH of water saturated with Ca2KNa(PO4)2 was 12.5
      when the material was mechanically activated but was only 9.5 for the untreated
      compound suggesting an increase in solubility following milling. The cements set
      following mixing with a 2.5% Na2HPO4 solution in clinically acceptable times
      between 5-12 min and showed compressive strengths of up to 11 MPa after 24 h
      setting. The strong alkaline pH value of the cements may provide antimicrobial
      potential for an application in dentistry as pulp capping agents or cavity liners
      or for the treatment of infected bone sites.

PMID- 15875253
TI  - In vivo assessment of hydroxyapatite and silicate-substituted hydroxyapatite
      granules using an ovine defect model.
AB  - Phase pure hydroxyapatite (HA) and two silicate-substituted hydroxyapatites (0.8
      and 1.5 wt% Si, or 2.6 and 4.9 wt% SiO4) were prepared by aqueous precipitation
      methods. The filter-cakes of HA and silicate-substituted hydroxyapatite (SiHA)
      compositions were processed into granules 1.0-2.0 mm in diameter and sintered at
      1200 degrees C for 2 h. The sintered granules underwent full structural
      characterisation, prior to assessment in an ovine defect model by implantation
      for a period of 6 and 12 weeks. The results indicate that HA and SiHA implants
      were well accepted by the host tissue, with no evidence of inflammation. New bone
      formation was observed directly on the surfaces and in the spaces between the
      granular implants. Quantitative histomorphometry as determined by the percentage
      of bone ingrowth and bone coverage for both SiHA implant compositions was
      significantly greater than that for phase pure HA. These findings indicate that
      the in vivo bioactivity of hydroxyapatite was significantly improved by the
      incorporation of silicate ions into the HA structure, making SiHA ceramics
      attractive alternatives to conventional HA materials for use as bone graft
      substitute ceramics.

PMID- 15875254
TI  - Influence of temperature and aging time on HA synthesized by the hydrothermal
      method.
AB  - The influence of temperature and aging time on the morphology and mechanical
      properties of nano-sized hydroxyapatite (HA) synthesized by a hydrothermal method
      is reported here. The pre-mixed reactants were poured into a stirred autoclave
      and reacted at temperatures between 25-250 degrees C for 2-10 h. HA powders thus
      obtained were examined using X-ray diffraction (XRD), high-resolution field
      emission scanning electron microscopy (FESEM) and a particle size analyzer. It
      was found that the aspect ratio of the particles increased with the reaction
      temperature. The length of the HA particles increased with the reaction
      temperature below 170 degrees C, but it decreased when the temperature was raised
      above 170 degrees C. The agglomerates of HA particles were formed during
      synthesis, and their sizes were strongly dependent on reaction temperatures. As
      the reaction temperature increased, the agglomerate size decreased (p = 0.008).
      The density of the discs pressed from these samples reached 85-90% of the
      theoretical density after sintering at 1200 degrees C for 1 h. No decomposition
      to other calcium phosphates was detected at this sintering temperature. A
      correlation existed (p = 0.05) between the agglomerate sizes of HA particles
      synthesized at various conditions and their sintered densities. With the increase
      of the agglomerate size, the sintered density of the HA compact decreased. It was
      found that both the sintered density and flexural strength increased with
      increasing aging time and reaction temperature. A maximum flexural strength of 78
      MPa was observed for the samples synthesized at 170 degrees C for 5 h with the
      predicted average at these conditions being 65 MPa. These samples attained an
      average sintered density of 88%.

PMID- 15875255
TI  - Incorporation of fluorine ions into hydroxyapatite by a pH cycling method.
AB  - Fluorine ions were incorporated into hydroxyapatite (HA) using a pH cycling
      method and the resulting materials were studied using transmission electron
      microscopy (TEM), X-ray diffraction (XRD), and electrochemical analysis. TEM
      observations showed that fluoridated hydroxyapatite (FHA) nanoparticles with a
      narrow particle size distribution were obtained at several different levels of
      fluorine incorporation. Significant particle growth was observed following
      calcining at 1200 degrees C. The TEM data revealed that, instead of forming
      laminated structures, a mixture of HA and FA was obtained, and that this mixture
      transformed into a single homogeneous FHA phase upon heating. It was found that
      the efficiency of fluorine incorporation did not vary significantly with the
      initial HA particle size, but increased as the fluorine content of the initial
      solution was increased. A relatively low fluorine incorporation efficiency,
      approximately 60%, was attained for most of the FHA samples and this was
      attributed to the short holding time at each pH cycle and the limited number of
      pH cycles employed in the current study.

PMID- 15875256
TI  - Cement from magnesium substituted hydroxyapatite.
AB  - Brushite cement may be used as a bone graft material and is more soluble than
      apatite in physiological conditions. Consequently it is considerably more
      resorbable in vivo than apatite forming cements. Brushite cement formation has
      previously been reported by our group following the mixture of nanocrystalline
      hydroxyapatite and phosphoric acid. In this study, brushite cement was formed
      from the reaction of nanocrystalline magnesium-substituted hydroxyapatite with
      phosphoric acid in an attempt to produce a magnesium substituted brushite cement.
      The presence of magnesium was shown to have a strong effect on cement composition
      and strength. Additionally the presence of magnesium in brushite cement was found
      to reduce the extent of brushite hydrolysis resulting in the formation of HA. By
      incorporating magnesium ions in the apatite reactant structure the concentration
      of magnesium ions in the liquid phase of the cement was controlled by the
      dissolution rate of the apatite. This approach may be used to supply other ions
      to cement systems during setting as a means to manipulate the clinical
      performance and characteristics of brushite cements.

PMID- 15875258
TI  - Microporosity enhances bioactivity of synthetic bone graft substitutes.
AB  - This paper describes an investigation into the influence of microporosity on
      early osseointegration and final bone volume within porous hydroxyapatite (HA)
      bone graft substitutes (BGS). Four paired grades of BGS were studied, two (HA70-1
      and HA70-2) with a nominal total porosity of 70% and two (HA80-1 and HA80-2) with
      a total-porosity of 80%. Within each of the total-porosity paired grades the
      nominal volume fraction of microporosity within the HA struts was varied such
      that the strut porosity of HA70-1 and HA80-1 was 10% while the strut-porosity of
      HA70-2 and HA80-2 was 20%. Cylindrical specimens, 4.5 mm diameter x 6.5 mm
      length, were implanted in the femoral condyle of 6 month New Zealand White
      rabbits and retrieved for histological, histomorphometric, and mechanical
      analysis at 1, 3, 12 and 24 weeks. Histological observations demonstrated
      variation in the degree of capillary penetration at 1 week and bone morphology
      within scaffolds 3-24 weeks. Moreover, histomorphometry demonstrated a
      significant increase in bone volume within 20% strut-porosity scaffolds at 3
      weeks and that the mineral apposition rate within these scaffolds over the 1-2
      week period was significantly higher. However, an elevated level of bone volume
      was only maintained at 24 weeks in HA80-2 and there was no significant difference
      in bone volume at either 12 or 24 weeks for 70% total-porosity scaffolds. The
      results of mechanical testing suggested that this disparity in behaviour between
      70 and 80% total-porosity scaffolds may have reflected variations in scaffold
      mechanics and the degree of reinforcement conferred to the bone-BGS composite
      once fully integrated. Together these results indicate that manipulation of the
      levels of microporosity within a BGS can be used to accelerate osseointegration
      and elevate the equilibrium volume of bone.

PMID- 15875257
TI  - Ammonium hexafluorosilicate increased acid resistance of bovine enamel and
      dentine.
AB  - Although diamine silver fluoride (AgF: (NH3)2AgF) stains teeth black, it is known
      as a very effective agent to prevent the dental caries progress. In order to find
      another fluoride that has a similar anticariogenic effect without changing tooth
      color, we prepared ammonium hexafluorosilicate (SiF: (NH4)2SiF6), in which the
      silver of AgF is replaced with silicon. In this study, the anticariogenic effect
      of SiF was evaluated using bovine teeth. Fluoride solutions, SiF, AgF, acidulated
      phosphate fluoride (APF), and sodium fluoride (NaF), were applied to bovine
      enamel and dentine blocks, and the depth of demineralization was measured after
      exposure to a demineralizing solution for 24 h. Also, fluoride was applied to a
      simulated dentine caries specimen to evaluate the caries progress-preventing
      ability. For the dentine specimens, mineral loss (Delta Z) was also measured with
      microradiography. We found that SiF treated enamel showed better acid resistance
      than specimens treated with NaF or APF. AgF treated enamel also showed similar
      acid resistance, but was stained black. SiF and AgF treated caries-affected
      dentine showed reduced demineralization when exposed to a demineralization
      solution for 24 h. Mineral loss (Delta Z) was reduced to 85% and 75%,
      respectively. Although the acid resistance of the SiF treated teeth was inferior
      to that of the AgF treated teeth, we consider that SiF has good potential as
      anticariogenic agent, since it increased acid resistance without changing tooth
      color.

PMID- 15875260
TI  - [Exposure to tobacco smoke (passive smoking) in the home and inpatient treatment
      of children under the age of 5 years in Germany].
AB  - BACKGROUND AND OBJECTIVE: Exposure to environmental tobacco smoke (ETS) poses an
      impact on the health of the newborns and infants. In Germany research about the
      tobacco-attributable morbidity and mortality has been conducted to a very small
      extent. This analysis examines all data from 16 federal states in regard to
      number and duration of hospitalization of children exposed to ETS up to 5 years
      of age. MATERIAL AND METHODS: Integration of two different data sets: (a)
      national data (number of households with children younger than 5 years exposed to
      a current smoker) with (b) hospital statistics (number and duration of
      hospitalisations by diagnoses) for all 16 federal states. Relative risks for
      tobacco-attributable diseases were taken from current research. RESULTS: In
      Germany the rate for tobacco-attributable hospitalisations of children between 0
      and < 5 years range from 1.6 % to 3.8 % between states. Between 22.0 % and 27.1 %
      of all hospitalisations with the diagnosis of otitis media or respiratory
      diseases are attributable to passive smoking. CONCLUSION: Tobacco-attributable
      hospitalisations pose a serious but preventable problem for the health care
      system.

PMID- 15875259
TI  - Degenerative mineralization in the fibrous capsule of silicone breast implants.
AB  - The formation of a fibrous capsule made of long collagen fibers surrounding
      breast implants represents an unavoidable phenomenon as the patient's reaction to
      the presence of a foreign body. Depending upon the size and shape of the implants
      and the chemicals percolating through the shell, this fibrous capsule is
      continuously remodeled. The compaction of the foreign debris in the vicinity of
      the silicone shell is followed by the loss of cellular activity, shrinkage and
      necrosis. Calcification is the ultimate step. These phenomena were illustrated in
      the analysis of 18 explanted breast prostheses after 20 or more years of
      implantation. The degenerative mineralization was shown in scanning electron
      microscopy and light microscopy. The minerals proved to be bone-like
      hydroxyapatite by X-ray diffraction and Solid State NMR analysis. Whatever the
      characteristics of any sophisticated new model of breast implant, phenomenon of
      mineralization might be minimized but it is very unlikely that it would be
      totally eliminated.

PMID- 15875261
TI  - [Minimally-invasive regional treatment of a symptomatic ischial metastasis using
      radiofrequency ablation and osteoplasty].
AB  - HISTORY AND ADMISSION FINDINGS: A 46-year-old woman presented with worsening,
      morphine-resistant pain during the previous 8 weeks in the right ischium which
      rendered her immobile. The patient refused further surgery, radiotherapy or
      chemotherapy, as she had been treated for ovarian cancer and recurring rectal
      carcinoma with peritoneal carcinomatosis for the last three years almost without
      interruption and experienced several complications. The pelvic region had
      radiotherapy up to 70,4 Gy. INVESTIGATION: Scintigraphy of the bone showed
      enhancement in the right ischium. Conventional radiography demonstrated an
      irregular lesion with destruction of the corticalis 3 x 4 cm in size. Computed
      tomography revealed numerous microfractures and pseudo-arthritic changes. Needle
      biopsy confirmed a bone metastasis from the rectal carcinoma. Examination of
      radiation fields showed a high risk for radiation damage using conventional
      fractionation. TREATMENT AND COURSE: After achieving an interdisciplinary
      consensus the metastatic lesion of the patient under analgesia and sedation was
      thermo-ablated by using radiofrequency percutaneously under ct-control and filled
      with bone cement. 8 days later the patient was released from hospital pain-free
      and mobile. Her Karnofsky index rose from 30 % to 90 %. Morphine could be reduced
      to zero. No complications occurred. 9 month later, though newly appearing lung
      metastasis, the lesion of the ischium was still asymptomatic and stable and
      conventional radiography did not indicate local tumor progress or dislocated bone
      cement. The patient now agreed to further chemotherapy. CONCLUSION: Palliative
      minimally invasive radiofrequency ablation with concurrent osteoplasty can be
      effective in individual cases giving a better quality of life and mobility.
      Benefits and risks should be carefully evaluated in studies examining quality of
      life, especially in patients without the options of surgical and radiotherapy.

PMID- 15875262
TI  - [Diastolic heart failure -- case report].

PMID- 15875263
TI  - [Diastolic heart failure -- diagnostics].

PMID- 15875264
TI  - [Diastolic heart failure -- therapy].

PMID- 15875267
TI  - [Trigeminal autonomic headache, hemicrania continua and hypnic headache. A review
      of rare primary headache forms].
AB  - Tension-type headache and migraine are the most common types of primary
      headaches. Apart from these well known diseases, the group of primary headaches
      includes other relatively rare headache disorders. Some of these seldom syndromes
      have been described for the first time within the last twenty years and have been
      newly included in the revised IHS classification from 2004. Their typical
      symptomatic is less known, but offers an excellent opportunity to diagnose these
      syndromes. The importance of recognising these disorders is underlined by the
      fact, that rare primary headaches response often complete and rapid to a specific
      treatment. This review summarizes the current knowledge on the clinical
      presentation and treatment of cluster headache, paroxysmal hemicrania, SUNCT
      syndrome, hemicrania continua and hypnic headache.

PMID- 15875268
TI  - [Richard Siebeck--an important exponent of the "Heidelberg School." A look back
      at a great physician in the 40th year after his death].

PMID- 15875270
TI  - [Does the "customer orientation" bring a benefit to the patients?].

PMID- 15875269
TI  - [Does depot penicillin over a long term increase the antistreptolysin titer?].

PMID- 15875271
TI  - [Assessment of spirituality/religiosity in the context of health related quality
      of life].
AB  - Patients' evaluations of their health status (health related quality of life,
      HRQOL) are increasingly taken into account in medical research and practice. In
      the Anglo-American literature a growing interest in including the life domain
      "spirituality/religiosity" as a component of HRQOL is observed. German studies in
      this research area are still scarce. As a guidance for further research, this
      paper gives an overview of instruments for the assessment of
      spirituality/religiosity in the context of HRQOL-research. Special attention is
      payed to German scales and adaptations. Since only few of the established
      multidimensional HRQOL-instruments include spirituality/religiosity, several
      short scales are described that allow additional assessment of
      spirituality/religiosity in an economical way.

PMID- 15875272
TI  - [Bronchial asthma and mental disorders -- a systematic review of empirical
      studies].
AB  - Bronchial asthma occurs independently from gender and in all age groups belonging
      to the frequent diseases with a high demand for treatment. A part of those
      affected suffer from comorbid mental burden and disorders. The review analyses
      studies investigating the prevalence of mental burden and disorders in patients
      with bronchial asthma. The database MEDLINE was searched for studies published
      from 1980 to 2002. Patients with bronchial asthma frequently show mood and
      anxiety disorders, with prevalence rates up to 41 % and 52 %. There is no
      significant correlation between the severity of asthma and the existence of a
      mental burden or disorder. However, persons with difficult-to-treat asthma
      (brittle asthma) show more mental burden than patients with controllable
      symptoms. Compliant patients show a lower prevalence rate of depressive burden
      than noncompliant patients. The reviewed studies are very heterogeneous with
      respect to their methodology and the investigated samples limiting the
      interpretation of their results significantly. In the future more well-designed
      epidemiological studies have to be performed to achieve valid and representative
      conclusions about the prevalence rates of mental burden and disorders in patients
      with bronchial asthma.

PMID- 15875273
TI  - [Help and advice for people with exceptional experiences].
AB  - The results of numerous surveys show that Exceptional Experiences (EE) belong to
      a human body of knowledge which is historically as well as trans-culturally
      common. They are frequent within the normal population . Although people with
      these experiences may develop irritations and alienations requiring treatment in
      consequence, the medical and psychosocial health care system hardly offers any
      competent help. In our study data were collected to better understand the
      clientele, their needs and the reported phenomena. In addition, data show the
      specific need for care in that area. Starting from N = 858 cases which were taken
      care of within the years of 1996 and 2000, sociodemographic data and mental
      health problems of this specific clientele are described. Moreover typical
      patterns of EE which were found by factor analysis are presented. Based on these
      patterns different EE-specific types of clients can be distinguished.

PMID- 15875274
TI  - [Evaluation of the short-form social support questionnaire (SOZU-K-22) in
      clinical and non-clinical samples].
AB  - Three versions (22-item, 10-item, and 7-item) of the social support questionnaire
      (F-SOZU) were psychometrically evaluated in two clinical and three non-clinical
      Austrian samples. The distribution of sum scores in all three versions was
      negatively skewed; means on the item-level were in the upper region of the five
      point scale (M > 4.0) in all non-clinical samples. Internal consistency estimates
      were found to be satisfying for the total test scores (alpha > 0.85). The 10-item
      and the 7-item forms correlated highly with the 22-item form total score (r >
      0.90). Principal components analysis supported a one dimensional solution in all
      forms. The discussion focuses on the problem of the highly skewed test scores. It
      is also argued that the use of the 7-item version might be preferable and more
      efficient if the researcher is only interested in obtaining a global score for
      perceived social support.

PMID- 15875275
TI  - [Polypharmacological approach to progressive chronic kidney disease: the new
      scenery].
AB  - End-stage renal disease (ESRD) is a social and economical threat worldwide. Much
      has been done in previous decades to develop new treatments, but we remain a long
      way from being satisfied. Recently, growing attention has been paid to
      polytherapeutic approaches to chronic kidney disease (CKD) to control different
      causal factors involved in progression and in the meantime, and reduce them as
      much as possible. Starting from a paper published in the British Medical Journal,
      which suggested the use of a polypill to prevent cardiovascular events in the
      general population, I tried to apply a similar approach in the nephrology
      setting, focusing my attention on therapeutic strategies to slow down CKD
      progression, which could possibly be included in a 'anti-dialysis polypill'.
      Among these strategies, I selected the effect of the inhibition of the renin
      angiotensin system, the use of statins and anemia correction. Unfortunately, this
      approach is not applicable theoretically, due to the lack of a sufficient number
      of randomized clinical trials calculating the relative risk, in particular
      concerning the use of statins and the treatment of anemia. However, while
      awaiting new therapeutical approaches to be more selective and efficacious, a
      treatment combination seems to be, together with better implementation of single
      therapies, the only possible strategy to apply.

PMID- 15875276
TI  - [Early therapeutic education in chronic renal disease: a new approach].
AB  - Chronic renal failure (CRF) remains a significant problem. Early referral of
      patients reduces cardiovascular risk and allows better quality of life and life
      expectancy. Uremic patients represent a typical example of chronic disease, which
      requires multidisciplinary team involvement and stratification of treatment
      processes. During the evolution of the disease to chronicity, the patient
      requires different clinical approaches that form part of a unique treatment
      process, involving day-to-day management, carried out by the general
      practitioner, as well as the handling of acute events requiring specialized
      clinical management. Early referral essentially requires three steps. The first
      step is therapeutic education, which includes information, sensitiveness,
      training and acceptance of the disease. The second step is the assembling of a
      multidisciplinary team in which the members are able to work together,
      coordinating and managing treatment protocols. These two steps allow the design
      of the third step, disease management, which consists of a methodology based on
      an integrated approach to the dis-ease allowing continuous improvement in medical
      care, in the patient's quality of life and a better use of economic resources.

PMID- 15875277
TI  - [Role of immunity and tolerance in renal diseases].
AB  - Dendritic cells (DC) have been recognized as the most efficient antigen
      presenting cells that have the capacity to initiate naive T-cell response in
      vitro and in vivo. During their differentiation and maturation pathways, DC can
      efficiently capture, process and present antigens for T-cell activation. These
      characteristics make DC an attractive choice as the cellular adjuvant for can-cer
      vaccines. In humans, two DC subsets, myeloid DC (mDC) and plasmacytoid DC (pDC),
      have been characterized and have distinct origins and functions: mDC are involved
      in the induction of the Th1 response, while pDC regulate immunity and initiate
      adaptive antiviral immune responses. Advances in DC generation, loading and
      maturation methodologies have made it possible to generate clinical grade
      vaccines for various human trials. Several studies have shown that tumor antigen
      loaded DC vaccination is safe and promising for the treatment of cancer. We are
      investigating the use of autologous tumor lysate-pulsed mature DC in renal cancer
      patients with metastasis. DC can play a central role in the development of T-cell
      tolerance, and its maintenance in the periphery is critical for the prevention of
      autoimmunity. DC are likely to have a role in the pathogenesis of autoimmunity
      and are, to date, the only APC capable of provoking autoimmune disease. Systemic
      lupus erythematosus (SLE), a systemic autoimmune disease with multi-organ
      involvement with autoreactive T and B cells, could be due to DC alterations, and
      pDC have a potential role in this disease. Given their pivotal role in
      controlling immunity, DC are logical targets for treating both cancer and
      autoimmune diseases.

PMID- 15875279
TI  - [An unusual case of microhematuria].
AB  - Microhematuria is nearly always due to renal parenchymal or genito-urinary
      damage, with few exceptions. We report a case of microhematuria due to vascular
      anomaly. The diagnosis was realized making use of several imaging techniques.

PMID- 15875278
TI  - [Standardization criteria to ensure the uniformity of data collection by the
      Italian Registry of Dialysis and Transplantation].
AB  - The Italian Registry of Dialysis and Transplantation (RIDT) collects data
      concerning patients in renal replacement therapy (RRT) sent from Regional
      Registries. Until 2003, the data were sent in summary tables. From 2004, each
      region has been sending patient data as single non-summarized forms (i.e. one
      record for each patient). This paper summarizes the collection criteria and the
      ideal method to codify data ensuring that data sent to the RIDT are consistent.
      This standardization process is necessary to ensure the statistical analyzability
      of the data and their comparability with data from other registries. Moreover,
      the standardization process is the initial step in allowing the RIDT to obtain
      clinical data to transform the registry from an epidemiological registry to a
      clinical governance instrument.

PMID- 15875280
TI  - [From the Mailing List SIN: peritoneal sclerosis].
AB  - In the course of previous months, in the Mailing List of the Italian Society of
      Nephrology (ML-SIN), a message asking for opinions on the diagnosis and treatment
      of peritoneal sclerosis, gave rise to an extensive debate concerning this
      clinically interesting topic. The discussion evidenced significant differences
      both in the reported onset of clinical manifestations, emphasizing the difficulty
      in obtaining a definite early diagnosis, and in therapy approaches. This is
      sometimes limited to medical treatment, but surgery, although burdened with
      elevated complexity and a high mortality rate, mainly due to post-operative
      complications, is usually advocated for intestinal obstruction. In this issue of
      the review dedicated to the ML-SIN, two expert colleagues will analyze the
      different aspects of peritoneal sclerosis. The argument is developed in two
      sections: the first section is dedicated to the discussion of definition,
      etiology, pathology and clinical characteristics of this serious complication in
      peritoneal dialysis (PD).

PMID- 15875282
TI  - 2nd World Congress on Regenerative Medicine, 18-20 May 2005, Leipzig, Germany.
      Abstracts.

PMID- 15875281
TI  - [Angiodysplasia of the small bowel: a possible cause of anemia even in mild
      chronic renal failure].
AB  - BACKGROUND: Gastroenteric angiodysplasia (AD) is a vascular lesion characterized
      by vascular ectasias to the submucous sheath of the gastrointestinal tract.
      Lesions can be flat or raised, isolated or grouped and can break or ulcerate
      causing acute hemorrhage or, more commonly, chronic bleeding. CASE-REPORT: We
      describe a 65-year-old patient with a 3-yr history of chronic renal failure
      (CRF), who gradually developed anemia (hemoglobin (Hb) 10 g/dl) without any
      episodes of clinically relevant bleeding or any exposure to bleeding risk
      factors. Blood pressure (BP) was normal and renal function was stable (serum
      creatinine (Cr) 1.9 mg/dl). Routine laboratory tests showed a slight reduction in
      serum iron and transferrin saturation and a slightly elevated absolute
      reticulocyte count. These findings were associated with a positive occult
      gastrointestinal blood test and raised the clinical suspicion of chronic
      gastrointestinal blood loss. Oesophagogastro-duodenoscopy and colonoscopy
      demonstrated an absence of significant lesions, suggesting the need to
      investigate for a lesion localized in the small intestine. Capsular endoscopy, a
      recently developed endoscopic technique, particularly suited for small bowel
      pathology, was performed, and demonstrated the presence of an angiodysplasic
      lesion, located in the jejunum. CONCLUSIONS: Our case report supports the
      necessity for a complete clinical and laboratory evaluation of the possible
      causes of anemia superimposed on relative erythropoietin deficiency in CRF
      patients. When gastrointestinal blood loss is suspected, the entire gastroenteric
      tract should be examined to search for the bleeding sites. Our report also
      demonstrates that AD could be responsible for gastrointestinal bleeding even in
      mild CRF and not only, as usually reported, in end-stage renal disease (ESRD).
      Capsular endoscopy offers the unique possibility to determine the bleeding site
      in the small intestine and appears as an effective diagnostic procedure in CRF
      patients.

PMID- 15875284
TI  - Germany's reforms have yet to deliver insurance savings.

PMID- 15875285
TI  - Minority health care remains a problem for Canada's leaders.

PMID- 15875286
TI  - The unspoken issue that haunts the UK general election.

PMID- 15875287
TI  - A US-led Peace Corps for Health.

PMID- 15875288
TI  - America's new "food pyramid".

PMID- 15875289
TI  - Clues to target Notch2 in medulloblastoma.

PMID- 15875291
TI  - Bibliography. Current world literature. Lung and mediastinum.

PMID- 15875290
TI  - Introduction: Culture and sleep in children.

PMID- 15875292
TI  - Practice parameters for the management of rectal cancer (revised).
AB  - The American Society of Colon and Rectal Surgeons is dedicated to assuring high
      quality patient care by advancing the science, prevention, and management of
      disorders and diseases of the colon, rectum, and anus. The Standards Committee is
      composed of Society members who are chosen because they have demonstrated
      expertise in the specialty of colon and rectal surgery. This Committee was
      created to lead international efforts in defining quality care for conditions
      related to the colon, rectum, and anus. This is accompanied by developing
      Clinical Practice Guidelines based on the best available evidence. These
      guidelines are inclusive, and not prescriptive. Their purpose is to provide
      information on which decisions can be made, rather than dictate a specific form
      of treatment. These guidelines are intended for the use of all practitioners,
      health care workers, and patients who desire information about the management of
      the conditions addressed by the topics covered in these guidelines. It should be
      recognized that these guidelines should not be deemed inclusive of all proper
      methods of care or exclusive of methods of care reasonably directed to obtaining
      the same results. The ultimate judgment regarding the propriety of any specific
      procedure must be made by the physician in light of all of the circumstances
      presented by the individual patient.

PMID- 15875293
TI  - Joseph M. Matthews Oration. Globalization comes to colon and rectal surgery.

PMID- 15875294
TI  - Long-term outcomes of transanal rectocele repair.
AB  - PURPOSE: This study was designed to assess the risk of rectocele recurrence after
      transanal repair and identify its predictive factors. METHODS: A series of 71
      females who had undergone transanal repair of low isolated rectocele was
      retrospectively reviewed. The functional outcome was assessed by a standard
      questionnaire. The follow-up varied from 30 to 128 (mean, 74 +/- 30) months.
      Recurrences were evaluated by survival-analysis methods, and Cox's proportional
      hazar model was used to determine the optimal predictive factor for recurrence.
      RESULTS: Twenty-nine of 71 patients had isolated low rectocele recurrence, and 6
      had a rectocele recurrence associated to an enterocele occurrence. The optimal
      predictive factor for rectocele recurrence was the persistence of symptoms two
      months after surgery. Although correlated to recurrences, preoperative manual
      pressure during defecation was not an independent predictive factor for
      recurrences. Preoperative defecographic parameters do not seem to influence
      clinical outcome of surgery, and preoperative manometric values did not determine
      which females could develop anal incontinence several years after surgery.
      CONCLUSIONS: The results of the transanal rectocele repair might progressively be
      worse during the length of the follow-up with a high recurrence rate (50
      percent). Preoperative clinic, defecographic, or manometric parameters are not
      useful to identify females at risk for recurrence.

PMID- 15875295
TI  - The effect of pudendal block on voiding after hemorrhoidectomy.
AB  - PURPOSE: Urinary retention in common benign anal surgery is a burden to
      ambulatory surgery. A pudendal nerve block was used in hemorrhoid surgery to
      reduce voiding complications. METHODS: The effects of a pudendal nerve block in
      anal surgery were compared with those of spinal anesthesia. In this prospective
      study, 163 consecutive patients who underwent elective hemorrhoids surgery by a
      single surgeon were randomized to receive pudendal nerve block (pudendal group)
      with 0.5 percent bupivacaine (n = 81) with 1:20,000 epinephrine or spinal
      anesthesia (spinal group) with 0.5 percentbupivacaine (n = 82). RESULTS: There
      were no statistically significant differences in the patient demographics, total
      amount of fluid administered, time to the onset of anesthesia, or intraoperative
      pain. All patients had a successful block during surgery. However, puborectalis
      muscle relaxation was not complete in the pudendal group. The time from the
      injection of the anesthetics to the first sensation of pain was longer in the
      pudendal group (9.1 vs. 3.1 hours; P < 0.001). Urinary catheterization was
      required in only 6 patients in the pudendal group compared with 57 patients in
      the spinal group (P < 0.001). The degree of pain was significantly lower in the
      pudendal group (2.7 vs. 5.2, Visual Analog Scale; P < 0.001). The amount of
      analgesics injected was significantly lower in the pudendal group (16/81 vs.
      45/82; P < 0.001). CONCLUSIONS: A pudendal nerve block with bupivacaine results
      in fewer postoperative voiding complications and less pain compared with the
      traditional spinal anesthesia in a hemorrhoidectomy.

PMID- 15875296
TI  - Lavage enhances the production of proinflammatory mediators by peritoneal
      mesothelial cells in an experimental model.
AB  - PURPOSE: There is a lack of clinical evidence supporting the use of lavage in
      patients with peritonitis. It is known that fluids such as normal saline cause
      temporary damage to the peritoneum and that increased production of
      proinflammatory mediators is associated with a poor outcome. This study used an
      experimental model to evaluate the effect of lavage on the peritoneal mesothelium
      and the ability of peritoneal mesothelial cells to produce a battery of
      proinflammatory mediators (TNFalpha, IL-1beta, GROalpha, and ICAM-I.). METHODS:
      Wistar rats were allocated into four groups (control, peritonitis, lavage,
      peritonitis plus lavage). Peritonitis was induced by exposure to zymosan and
      saline was used for lavage. After 18, 24, and 43 hours, mesothelial imprints were
      taken from the peritoneum for histology, semiquantitative reverse transcription
      polymerase chain reaction, Western blot analyses, and immunocytochemistry.
      RESULTS: Both peritonitis and lavage caused peritoneal damage at 18 and 24 hours,
      and this effect was additive. At varying times, peritoneal mesothelial cells from
      animals undergoing lavage had greater up-regulation (P < 0.05) of mRNA expression
      for TNFalpha, IL-1beta, GROalpha, and ICAM-I and greater production (P < 0.05) of
      TNFalpha, IL-1RII, GROalpha, and ICAM-I. The latter was heavily concentrated at
      the cell membrane. CONCLUSIONS: Lavage causes self-limiting peritoneal damage and
      this is associated with an up-regulation of proinflammatory mediators in animals
      with peritonitis.

PMID- 15875297
TI  - A 49-year-old male with acute superior mesenteric artery occlusion during active
      ulcerative colitis: report of a case.

PMID- 15875298
TI  - Actinomycosis, a rare and unsuspected cause of anal fistulous abscess: report of
      three cases and review of the literature.
AB  - Primary perianal actinomycosis is rare. Sporadic cases, with lesions varying in
      extent have been reported. The infection is caused by the bacterium Actinomyces,
      which often is a saprophyte. Male gender and diabetes are risk factors, but the
      exact pathogenic mechanism remains speculative. The diagnosis is a challenge and
      often delayed, with a protracted history of masses and sinuses extending into the
      gluteal and genital region. The treatment, a combination of surgery and
      antibiotics, is poorly standardized. We report three cases and compare their
      characteristics to those of published cases, found by a computerized literature
      search (1968-2002). The lesions, a simple fistula-in-ano or a mass, were
      diagnosed in an early stage in all three patients. The infection always spread
      into the scrotum. There were no risk factors other than gender, except in one
      patient. The diagnosis was suspected by the observation of draining sulfur
      granules and promptly confirmed by histology in the three cases. All patients
      healed with antibiotics in addition to simple surgical procedures. Treatment
      consisted of amoxicillin for two weeks in two cases and more extended
      antimicrobial treatment in the third. These findings are contrasting with the
      classic picture of perianal actinomycosis. It is concluded that perianal
      actinomycosis can occur in the absence of risk factors and that early diagnosis
      requires a high degree of suspicion. An infection with Actinomyces should be
      suspected in the presence of lesions containing watery purulent material with
      sulfur granules. The indication for extended antibiotherapy combined with
      sphincter damaging surgery may need to be revised in the presence of early
      detection.

PMID- 15875299
TI  - EU research: the battle begins.

PMID- 15875300
TI  - Phase-change materials: towards a universal memory?

PMID- 15875301
TI  - Optical devices: the friendly gas phase.

PMID- 15875302
TI  - Magnetic materials: the texture of frustrated magnets.

PMID- 15875303
TI  - Artificial skins: hierarchical wrinkling.

PMID- 15875304
TI  - Quantum criticality: a glimpse of a Luttinger liquid.

PMID- 15875305
TI  - Biomimetism and bioinspiration as tools for the design of innovative materials
      and systems.
AB  - Materials found in nature combine many inspiring properties such as
      sophistication, miniaturization, hierarchical organizations, hybridation,
      resistance and adaptability. Elucidating the basic components and building
      principles selected by evolution to propose more reliable, efficient and
      environment-respecting materials requires a multidisciplinary approach.

PMID- 15875306
TI  - Report from the 12th Retrovirus Conference. Acute and recent HIV infection.

PMID- 15875307
TI  - Report from the 12th Retrovirus Conference. Studies of approved antiretrovirals.

PMID- 15875308
TI  - Report from the 12th Retrovirus Conference. Treatment interruption and other
      novel treatment strategies.

PMID- 15875309
TI  - Report from the 12th Retrovirus Conference. Adherence.

PMID- 15875310
TI  - Report from the 12th Retrovirus Conference. Resistance.

PMID- 15875311
TI  - Report from the 12th Retrovirus Conference. New drugs.

PMID- 15875312
TI  - Report from the 12th Retrovirus Conference. Metabolic complications.

PMID- 15875313
TI  - Report from the 12th Retrovirus Conference. Hepatitis.

PMID- 15875314
TI  - Report from the 12th Retrovirus Conference. HIV/AIDS in resource-limited
      settings.

PMID- 15875315
TI  - Report from the 12th Retrovirus Conference. Tuberculosis.

PMID- 15875316
TI  - Fibroblast growth factor 2 and the transcription factor Egr-1 localise to
      endothelial cell microvascular channels in human coronary artery occlusion.

PMID- 15875317
TI  - Neuropharmacological therapy of polycythemia vera: roles of circulating
      catecholamines and serotonin.

PMID- 15875318
TI  - [Expression and significance of PTEN and nm23 in the metastasis of gallbladder
      cancer].
AB  - OBJECTIVE: To explore the relationship between the expressions of PTEN and the
      metastasis of the gallbladder cancer. METHODS: The expression of PTEN and nm23
      were detected by immunohistochemical staining in 32 cases of gallbladder cancer
      with metastasis and the staining intensity was scored semi-quantitatively,
      compared with the cases without metastasis. RESULTS: The intensity score of PTEN
      and nm23 in gallbladder cancer with metastasis was 8.9947+/-4.5590 and 10.2003+/
      3.9031, respectively, which was lower than that in those without metastasis
      (12.9433+/-4.7618 and 15.8436+/-5.6917 respectively, P < 0.01 ). The expression
      of PTEN was correlative with that of nm23 ( Pearson = 0.370, P < 0.05).
      CONCLUSION: The lower expressions of PTEN and nm23 are related to the metastasis
      of gallbladder cancer.

PMID- 15875319
TI  - [Clinical research on BIS for monitoring the depth of N2O and desflurane
      anesthesia].

PMID- 15875320
TI  - Rite of passage? Why young adults become uninsured and how new policies can help.
AB  - Young adults (ages 19 to 29) are one of the largest and fastest-growing segments
      of the U.S. population without health insurance: more than 13 million lacked
      coverage in 2003, an increase of 2.2 million since 2000. Young adults often lose
      coverage under their parents' policies at age 19, or when they graduate from high
      school or college. Nearly two of five college graduates and one-half of high
      school graduates who do not go on to college will be uninsured for a period
      during the first year after graduation. Three policy changes could extend
      coverage to uninsured young adults and prevent others from losing it: extending
      eligibility for dependents under private coverage through age 23; extending
      eligibility for Medicaid and the State Children's Health Insurance Program to age
      23; and ensuring that colleges and universities require full-and part-time
      students to have insurance, and that they offer coverage to both.

PMID- 15875321
TI  - Androgen deprivation increases neuronal nitric oxide metabolism and its
      vasodilator effect in rat mesenteric arteries.
AB  - This study examines the effects of male sex hormones on the vasoconstrictor
      response to electrical field stimulation (EFS), as well as neuronal NO modulation
      of this response. For this purpose, denuded superior mesenteric artery from
      orchidectomized and control male Sprague-Dawley rats was used. EFS induced
      similar frequency-dependent contractions in segments from both groups. The NO
      synthase (NOS) inhibitor N(omega)-nitro-L-arginine methyl ester strengthened EFS
      elicited contractions more in arteries from orchidectomized than from control
      male rats. The expression of nNOS was more pronounced in segments from control
      than from orchidectomized animals. Basal and EFS-induced NO release was similar
      in segments from both groups. In noradrenaline (NA)-precontracted segments,
      sodium nitroprusside (SNP) induced a concentration-dependent relaxation, that was
      greater in segments from orchidectomized than control male rats. 8-Bromo-cGMP
      induced a similar concentration-dependent relaxation in NA-precontracted segments
      from either group, and the cGMP levels induced by SNP were also similar in the
      two groups. Superoxide dismutase (SOD), a superoxide anion scavenger, did not
      modify the relaxation in segments from control male rats. In contrast, SOD
      enhanced the relaxation induced by SNP in segments from orchidectomized rats, and
      the effect was reversed by preincubation with SOD plus catalase. The generation
      of superoxide anion and of peroxynitrite was greater in segments from
      orchidectomized than control rats. In NA-precontracted segments from control or
      orchidectomized rats, exogenous peroxynitrite and H(2)O(2) induced a
      concentration-dependent relaxation. These results suggest that EFS induces a
      similar nNOS-derived NO release in segments from orchidectomized and control male
      rats, despite the decrease in nNOS expression in orchidectomized rats. The NO
      metabolism is higher in segments from orchidectomized male rats due to the
      increases in anion superoxide generation and peroxynitrite formation. The
      vasodilator effects of the peroxynitrite and H(2)O(2)0 generated from the NO
      metabolism are what enhance the functional role of the nNOS-derived NO release in
      the orchidectomized rats.

PMID- 15875323
TI  - Immunization coverage against invasive pneumococcal disease among children in the
      Capital Health Region of Alberta.

PMID- 15875322
TI  - What's in a name for memory errors? Implications and ethical issues arising from
      the use of the term "false memory" for errors in memory for details.
AB  - The term "false memories" has been used to refer to suggestibility experiments in
      which whole events are apparently confabulated and in media accounts of contested
      memories of childhood abuse. Since 1992 psychologists have increasingly used the
      term "false memory" when discussing memory errors for details, such as specific
      words within lists. Use of the term to refer to errors in details is a shift in
      language away from other terms used historically (e.g., "memory intrusions"). We
      empirically examine this shift in language and discuss implications of the new
      use of the term "false memories." Use of the term presents serious ethical
      challenges to the data-interpretation process by encouraging over-generalization
      and misapplication of research findings on word memory to social issues.

PMID- 15875324
TI  - Avian influenza, Vietnam.

PMID- 15875325
TI  - Salmonella enteritidis outbreak linked to a local bakery, British Columbia,
      Canada.

PMID- 15875326
TI  - Outbreak of Shigella flexneri and Shigella sonnei enterocolitis in men who have
      sex with men, Quebec, 1999 to 2001.

PMID- 15875327
TI  - Avian influenza, Vietnam--update.

PMID- 15875328
TI  - National standards for immunization coverage assessment: recommendations from the
      Canadian Immunization Registry Network.

PMID- 15875329
TI  - Avian influenza, Vietnam--update.

PMID- 15875330
TI  - An overview of peroxisomal biogenesis disorders.

PMID- 15875332
TI  - Proceedings of the Eleventh Conference on the Adrenal Cortex. June 12-15, 2004.
      New Orleans, Louisiana, USA.

PMID- 15875331
TI  - Efficient analysis of hepatic glucose output and insulin action using a liver
      slice culture system.
AB  - BACKGROUND: Liver slices have been reported to retain histological integrity and
      metabolic capacity for over 24 hours in flask culture systems, and they have been
      used for pharmacological and toxicological studies before. However, whether this
      method is suitable to measure hepatic glucose output is unknown. METHODS:
      Precision-cut liver slices were prepared from fresh male rat liver. After high
      glucose pre-incubation (11.2 mmol/l), medium was changed to low-glucose
      conditions (0.5 mmol/l). Glucose and lactate levels as well as aspartate
      aminotransferase activity were monitored for 50 minutes with or without addition
      of insulin (600 pmol/l) and/or epinephrine (0.5 micromol/l). Slice potassium
      content and histology were examined to prove liver viability. RESULTS: We
      observed a stable glucose production from the liver slices of 0.3-0.4 micromol/g
      liver/min. Epinephrine increased (by 82+/-30%) and insulin decreased (by 80+/-8%)
      liver slice glucose output. Significant signs of ischemia were not detected.
      CONCLUSIONS: Hepatic glucose release can be reliably measured in a liver slice
      culture system, and it is regulated by major hormone systems. This method may be
      helpful for further characterization of direct insulin action and resistance in a
      complex tissue as the liver; however, pharmacological applications such as the
      analysis of drug effects on hepatic glucose metabolism can also be envisioned.

PMID- 15875333
TI  - Recent advances and future directions in endocrine manipulation of breast cancer.
      Proceedings of the Fourth International Conference. July 21-22, 2004. Cambridge,
      Massachusetts, USA.

PMID- 15875334
TI  - Anastrozole: new indication. Adjuvant treatment of non metastatic breast cancer:
      useful for some patients.
AB  - (1) For postmenopausal women with hormone-receptor-positive breast cancer, the
      reference adjuvant treatment after surgical excision is tamoxifen (an anti
      estrogen), taken orally at a dose of 20 mg/day for 5 years. (2) Anastrozole is
      the first aromatase inhibitor to be licensed for this use in France. (3)
      Marketing authorisation was based on the short-term results of a double-blind
      trial comparing anastrozole (1 mg/day) with tamoxifen (20 mg/day) in 9366 women.
      The trial is planned to last five years. The results obtained after median follow
      up of 4 years showed no difference between the groups in overall survival (109
      deaths in each group). But first pathological events were significantly less
      frequent in the group taking anastrozole (13% versus 15%). Note that these
      results are undermined by a number of methodological flaws, including relatively
      short follow-up and definition of relapses using an endpoint mixing heterogeneous
      prognostic factors. (4) Musculoskeletal disorders, fractures (7.1% versus 4.4%)
      and hypercholesterolemia were statistically more common with anastrozole than
      with tamoxifen. Women taking anastrozole found their sex lives less satisfactory
      than women taking tamoxifen. The following adverse events were statistically less
      common with anastrozole than with tamoxifen: hot flushes (35.0% versus 40.3%),
      metrorrhagia, venous thromboembolism (1.1% versus 1.8%), ischaemic stroke (1.1%
      versus 2.3%), and endometrial cancer (3 versus 15 cases at 4 years). (5) In
      practice, anastrozole may be beneficial for women who cannot use tamoxifen, such
      as those at high risk of thrombosis. Anastrozole costs ten times more per day
      than tamoxifen. Tamoxifen remains the reference adjuvant treatment for all other
      women.

PMID- 15875335
TI  - American Psychiatric Association honors Dorothea Dix with first posthumous
      fellowship.

PMID- 15875336
TI  - Kaiser Commission Report addresses challenges of enrolling "dual eligibles" in
      new Medicare drug plans.

PMID- 15875337
TI  - Nasal sumatriptan: new dosage. For adolescents with migraine: too little benefit.
AB  - (1) The reference first-line drug therapy for migraine attacks in adolescents is
      a non specific analgesic such as paracetamol or a nonsteroidal antiinflammatory
      drug like ibuprofen. Two specific analgesics are authorised for use in this
      setting in France, namely ergotamine and dihydroergotamine. (2) Nasal sumatriptan
      is the first triptan to be licensed for this age group in France. (3) Evaluation
      data includes three flawed placebo-controlled trials. (4) Effects were modest at
      best. Only one of the three trials showed that sumatriptan was more likely than
      placebo to give complete pain relief within two hours. The three trials fail to
      show that sumatriptan is effective against symptoms such as nausea and vomiting,
      photophobia and phonophobia. (5) The principal known adverse effects of
      sumatriptan are chest tightness, flushing, and increased blood pressure. (6) In
      the only trial report containing relevant information, unpleasant taste was the
      only adverse effect more commonly associated with sumatriptan than with placebo.
      (7) Postmarketing follow-up revealed a number of serious adverse effects,
      including stroke, myocardial infarction and loss of vision. (8) The packs
      containing 6 or 12 spray vials carry a risk of overuse and self-induced headache.
      (9) In practice, sumatriptan must not be used to treat migraine attacks in
      adolescents.

PMID- 15875338
TI  - Bosentan: new preparation. Pulmonary hypertension: an option before epoprostenol
      infusion.
AB  - (1) Pulmonary hypertension is a progressive disorder characterised by abnormally
      high pulmonary artery pressure, leading to right ventricular failure and death,
      generally after a few years. (2) Treatment usually combines an anticoagulant,
      oxygen therapy, a diuretic and, sometimes a calcium channel blocker. Efficacy is
      poorly documented but appears to be limited. Long-term treatment with
      epoprostenol (prostacyclin), given as a continuous intravenous infusion via a
      central catheter and pump improves the quality of life of patients with severe
      pulmonary hypertension (NYHA classes III and IV, associated with discomfort
      during daily activities or even at rest). The impact of this treatment on
      survival seems to depend on the type of pulmonary hypertension: benefits were
      seen in a trial in patients with idiopathic pulmonary hypertension, while there
      was no effect in another trial in patients with pulmonary hypertension associated
      with scleroderma. Epoprostenol causes numerous adverse effects, some of which can
      be severe. (3) Marketing authorisation was recently granted in Europe for oral
      bosentan therapy for pulmonary arterial hypertension severe enough to restrict
      daily activities. (4) Two placebo-controlled trials lasting 12 to 16 weeks
      included 32 and 213 patients who responded inadequately to calcium channel
      blockers. They showed that the 6-minute walking distance improved by a median of
      76 metres and 44 metres, respectively. In the trial with 213 patients, 42% of
      patients in the bosentan group and 30% of those in the placebo group were
      improved according to the NHYA scale. No impact on survival was observed in these
      short trials. (5) A trial in 33 patients showed no difference in symptom
      improvement between groups treated with intravenous epoprostenol + oral bosentan
      or intravenous epoprostenol + oral placebo. (6) Two adverse effects require
      monitoring, namely anemia and elevated transaminase activity. Bosentan carries a
      risk of multiple pharmacokinetic interactions and is teratogenic in animals.
      Women taking bosentan cannot use hormone-based contraception, because of a
      pharmacokinetic interaction. (7) In practice, oral bosentan improves symptoms in
      patients whose daily activities are restricted by pulmonary arterial
      hypertension. Bosentan is easy to use, making it an option before continuous
      intravenous epoprostenol infusion, even though it may not be as effective.

PMID- 15875339
TI  - Children's competence for assent and consent: a review of empirical findings.
AB  - This narrative review summarizes the empirical literature on children's
      competence for consent and assent in research and treatment settings. Studies
      varied widely regarding methodology, particularly in the areas of participant
      sampling, situational context studied (e.g., psychological versus medical
      settings), procedures used (e.g., lab-based vs. real-world approaches), and
      measurement of competence. This review also identifies several fundamental
      dilemmas underlying approaches to children's informed consent. These dilemmas,
      including autonomy versus best interest approaches, legal versus psychological or
      ethical approaches, child- versus family-based approaches, and approaches that
      emphasize consent versus those that emphasize assent, have implications for the
      measurement of children's competence and interpretation of findings.
      Recommendations for future research in the area of children's informed consent
      include the use of diverse samples and control groups, development of
      multidimensional and standardized measures of competence, utilization of
      multidimensional and standardized measures of competence, utilization of
      observational methods and longitudinal designs, examination of noncognitive
      aspects of children's competence and comparison of children's competence for
      treatment and research decisions.

PMID- 15875340
TI  - Levodopa + carbidopa + entacapone. Entacapone: a second look: new preparations.
      Parkinson's disease: a modest effect.
AB  - (1) If patients with Parkinson's disease treated with levodopa develop end-of
      dose motor fluctuations, the standard therapy is to add bromocriptine, a dopamine
      receptor agonist, to their ongoing treatment. (2) Evaluation data available in
      1999 on entacapone, a catechol-o-methyltransferase (COMT) inhibitor, failed to
      show whether the balance of benefits versus harm was at least equivalent to that
      of bromocriptine. (3) Entacapone is now also available as a triple fixed-dose
      combination with levodopa + carbidopa. (4) Three double-blind trials have
      compared triple combinations of levodopa + carbidopa (or benserazide) +
      entacapone with levodopa + carbidopa (or benserazide) + placebo. Two of these
      trials showed an increase of about 1 hour in "on" phases during the day, together
      with a small reduction in the daily dose of levodopa. These results are
      consistent with earlier studies. (5) Entacapone has still not been compared with
      a dopamine agonist. (6) The fixed-dose combination of levodopa + carbidopa +
      entacapone has been compared with unfixed combinations in two unblinded trials
      only. (7) These two trials showed that efficacy was similar whether entacapone
      was used separately or included in a fixed-dose combination with levodopa +
      carbidopa. The only relevant trial (a non randomised cross-over trial) failed to
      show patient preference for the fixed-dose combination. (8) In France, a short
      acting combination of levodopa and carbidopa is available, with a dose ratio of
      10:1. This compares to a ratio of 4:1 for levodopa and carbidopa in the fixed
      dose combination of levodopa + carbidopa + entacapone. The dose of carbidopa is
      therefore higher for a given dose of levodopa, provoking more dyskinesias and
      nausea. (9) Entacapone can cause drowsiness. Cases of cholestatic hepatitis have
      also been reported. Risks of liver toxicity, rhabdomyolysis and neuroleptic
      malignant syndrome remain to be determined. (10) In practice, bromocriptine
      remains the first-choice for adjunctive therapy when levodopa becomes
      ineffective.

PMID- 15875341
TI  - Emtricitabine: new preparation. An antiretroviral very similar to lamivudine.
AB  - (1) The current first-line treatment for HIV infection is a combination of at
      least two nucleoside (or nucleotide) inhibitors of HIV reverse transcriptase, and
      one non nucleoside inhibitor or at least one HIV protease inhibitor. (2)
      Emtricitabine is the eighth nucleoside/nucleotide inhibitor to be marketed in
      France. It has a similar chemical structure to lamivudine. (3) Evaluation of
      emtricitabine use in adults contains data from four comparative trials, two in
      treatment-naive patients and two in patients who were already receiving a
      virologically effective treatment. Emtricitabine combination therapy was no more
      effective than lamivudine combination therapy on either viral load or the CD4+
      lymphocyte count. (4) Only non comparative trials are available in children. (5)
      In clinical trials, the adverse effects of emtricitabine were similar to those of
      lamivudine, including headache, pain, fatigue, fever, abdominal pain, nausea,
      vomiting, and diarrhea. (6) Viral strains resistant to emtricitabine are also
      resistant to lamivudine, and vice versa. (7) Emtricitabine, like other nucleoside
      inhibitors (lamivudine, didanosine, tenofovir), can be taken once a day by mouth.
      (8) In practice, emtricitabine is indistinguishable from lamivudine and does not
      offer any advance for patients living with HIV/AIDS.

PMID- 15875342
TI  - Stiripentol: new preparation. Severe myoclonic epilepsy of infancy: promising.
AB  - (1) Severe myoclonic epilepsy of infancy (Dravet's syndrome) is associated with
      multiple seizures and progressive onset of mental retardation. Available
      antiepileptics (valproic acid and clonazepam/clobazam) are only partially
      effective, even when used in combination. (2) Stiripentol is intended to be added
      to the valproate + clobazam combination when the latter is ineffective. (3) In a
      two-month double-blind trial, 9 of 21 infants remained seizure-free when
      stiripentol was added to the valproate-clobazam combination, whereas all 20
      infants receiving a placebo instead of stiripentol continued to have seizures.
      (4) Two follow-up studies lasting two and three years and involving 37 and 46
      children showed that about 20% of patients had a major benefit (fewer seizures)
      when stiripentol was added to inadequately effective valproate-clobazam
      combination therapy. The possible impact of stiripentol on psychomotor
      development is unknown. Stiripentol was only moderately effective in adolescents.
      (5) Stiripentol has common and sometimes serious adverse effects such as loss of
      appetite (with ensuing weight loss), drowsiness and insomnia. Stiripentol
      inhibits several cytochrome P450 isoenzymes, including CYP 3A4, creating a high
      risk of interactions, especially with co-administered antiepileptics. (6) The
      stiripentol dose strengths currently available in France are unsuitable for
      infants weighing less than 10 kg. (7) In practice, given the severity of this
      type of myoclonic epilepsy of infancy, the addition of stiripentol to ongoing but
      ineffective valproate-clobazam combination therapy is justified, even though the
      treatment is somewhat difficult to manage and has not yet been fully evaluated.

PMID- 15875343
TI  - Torsades de pointes with methadone.
AB  - (1) Methadone is an opiate used for replacement therapy of opiate addiction that
      causes dose-dependent QT prolongation. (2) Severe ventricular arrhythmias such as
      torsades de pointes have been reported, usually in patients on high doses (100 mg
      to 400 mg/day). (3) Methadone has a long plasma elimination half-life, and this
      poses a risk of accumulation. Accumulation is especially problematic when the
      dose is increased too rapidly. Combining methadone with a CYP 3A4 inhibitor
      increases the risk of torsades de pointes, as methadone is metabolised by this
      enzyme system. (4) Factors potentially predisposing patients to torsades de
      pointes must be analysed in each case; these include preexisting bradycardia,
      congenital QT prolongation, hypokalemia, and concomitant use of other drugs
      inducing QT prolongation. (5) This adverse effect has also been reported with
      levacetylmethadol (another opiate) and with heroin. It does not seem to occur
      with buprenorphine.

PMID- 15875344
TI  - Reversible Parkinsonism linked to trimetazidine.
AB  - A dozen cases of Parkinsonism linked to trimetazidine use have been reported in
      Spain. The symptoms resolved after treatment was stopped. Given trimetazidine's
      lack of established benefits, nothing justifies exposing patients to the least
      risk of this sort.

PMID- 15875345
TI  - Comparison of tracheal introducers.

PMID- 15875346
TI  - The use of Food and Drug Administration 510(k) notifications in patent
      litigation.
AB  - The U.S. Food and Drug Administration (FDA) 510(k) approval process provides
      medical device companies with the ability to market a device after the company
      establishes that the device to the marketed is "substantially equivalent" to one
      or more predicate devices. Companies that submit 510(k) notifications should be
      aware, however, that a 510(k) notification is a public document that may later
      reappear as evidence in patent litigation. Courts have considered 510(k)
      notifications to be relevant evidence in determining direct and contributory
      infringement, patent invalidity, and patent unenforceability due to inequitable
      conduct before the U.S. Patent and Trademark Office (USPTO). In one case, the
      court held that a substantial equivalence determination by FDA constituted
      evidence that can be "construed as an admission of infringement." The court also
      has relied on a 510(k) notification to support a finding of personal liability
      for a corporate officer who signed the 510(k) notification to be evidence of
      willful and deliberate conduct, and have awarded treble damages and reasonable
      attorney's fees to the prevailing party. The potential for increased risk in
      patent litigation is important for practitioners in the medical device industry,
      because more than seventy-five percent of medical devices are approved for
      marketing through the 510(k) process. This article reviews a number of patent
      cases in which a court has admitted a 510(k) notification as relevant evidence,
      and proposes general strategies for avoiding these situations.

PMID- 15875347
TI  - Drug marketing exclusivity under United States and European Union law.

PMID- 15875348
TI  - Legal implications of pharmacogenomics regarding drug trials, drug labeling, and
      genetic testing for drug prescription: an international approach.
AB  - Pharmacogenomics applies genomic technology to discover and develop drugs as well
      as to treat patients more effectively. This article addresses legal questions
      raised by pharmacogenomics, from drug development to drug use. Part II defines
      pharmacogenomics in further detail and explains the use of pharmacogenomics in
      drug development. Part III identifies potential legal questions raised by this
      approach to drug development and delivery. Parts IV to VIII offer possible
      solutions to these potential problems, analyzing the law in both the United
      States and the European Union (EU).

PMID- 15875349
TI  - Abstracts of the 105th Annual Meeting of the American Roentgen Ray Society. May
      15-20, 2005, New Orleans, Louisiana, USA.

PMID- 15875350
TI  - 2004 update--180-day exclusivity under the Hatch-Waxman amendments to the federal
      Food, Drug, and Cosmetic Act.
AB  - This article updates the author's previously published article on the topic,
      provides some insight into recent events in this area of the law, and specifies a
      few minor items that were noted incorrectly in the earlier work.

PMID- 15875351
TI  - Deterring the importation of counterfeit pharmaceutical products.

PMID- 15875352
TI  - Mandatory recall authority: a sensible and minimalist approach to improving food
      safety.

PMID- 15875353
TI  - The Federal Trade Commission's regulation of weight-loss advertising claims.

PMID- 15875354
TI  - IAGS proceedings. The biology of plaque and patient vulnerability. Panel
      discussion.

PMID- 15875355
TI  - Students and their teachers.

PMID- 15875356
TI  - Monitoring space shuttle air quality using the Jet Propulsion Laboratory
      electronic nose.
AB  - A miniature electronic nose (ENose) has been designed and built at the Jet
      Propulsion Laboratory (JPL), Pasadena, CA, and was designed to detect, identify,
      and quantify ten common contaminants and relative humidity changes. The sensing
      array includes 32 sensing films made from polymer carbon-black composites. Event
      identification and quantification were done using the Levenberg-Marquart
      nonlinear least squares method. After successful ground training, this ENose was
      used in a demonstration experiment aboard STS-95 (October-November, 1998), in
      which the ENose was operated continuously for six days and recorded the sensors'
      response to the air in the mid-deck. Air samples were collected daily and
      analyzed independently after the flight. Changes in shuttle-cabin humidity were
      detected and quantified by the JPL ENose; neither the ENose nor the air samples
      detected any of the contaminants on the target list. The device is microgravity
      insensitive.

PMID- 15875357
TI  - [Risk management--management, surgery and informed consent of outpatients-
      maxillary sinus lavage].

PMID- 15875358
TI  - Peristat: a computer-based perimetry self-test for cost-effective population
      screening of glaucoma.
AB  - PURPOSE: Peristat is a virtual perimetry system that allows self-testing on any
      standard computer monitor via Internet connection. The sensitivity and
      specificity of Peristat to detect visual-field defects were compared to standard
      Humphrey Visual Field Analyzer data. MATERIALS AND METHODS: In this prospective,
      comparative observational case series, 58 eyes of 33 patients were examined.
      Semiquantitative analyses compared Peristat and Humphrey Visual-Field scores. The
      study evaluated patients with an established glaucoma diagnosis, as well as
      glaucoma suspects who had undergone comprehensive ophthalmologic examinations
      including prior office perimetry evaluation (Humphrey Field Analyzer). Inclusion
      criteria were (1) diagnosis or suspicion of glaucoma, (2) BCVA better than
      20/200, (3) reliable performance on prior standardized office perimetry, and (4)
      CDR greater than 0.5. Computer literacy was not required, and more than 40% of
      the patients tested were computer illiterate, with no previous computer or
      Internet experience. A total of 58 eyes of 33 patients were tested with the
      Humphrey and the Peristat systems: 10 eyes of 5 patients without documented
      glaucomatous field loss and 48 eyes of 23 patients with mild-to-severe scotomas
      by standard 24-2 office perimetry. A standard computer setup was used with a 17"
      monitor, and the Peristat system was enabled through a remote connection with a
      server. RESULTS: All patients completed the Peristat test without difficulty.
      Testing time varied between 2 and 5 min, tending to be longer with more severe
      visual-field defects. Test results were reviewed, in a masked fashion, by two
      glaucoma specialists and one general ophthalmologist. The Peristat demonstrated a
      high degree of correlation with the Humphrey system. Among the three reviewers,
      sensitivity ranged from 80% to 83%. In a second subanalysis in which cases with
      mild defects were excluded, the Peristat's sensitivity increased to 84%-86% while
      specificity remained between 94% and 97% for all three reviewers. Patients
      performed the Peristat test with similar facility to their Humphrey test.
      Fixation losses and test reliability were comparable for both tests. CONCLUSIONS:
      Peristat is a reliable self-test perimetry system that demonstrates high clinical
      utility for the detection of visual-field defects from glaucoma. Peristat could
      be a valuable public health tool for cost-effective screening of glaucoma.

PMID- 15875359
TI  - Systemic interferon-gamma suppresses the development of endotoxin-induced uveitis
      in mice.
AB  - PURPOSE: It has been shown that interferon (IFN)-gamma is involved in the
      development of endotoxin-induced uveitis (EIU), but its exact role is unclear. We
      aimed to elucidate the role that endogenous systemic IFN-gamma plays in EIU
      pathogenesis. METHODS: EIU was induced in wild-type (WT) or IFN-gamma knockout
      (GKO) mice on the C57BL/6 background by injecting Salmonella typhimurium
      endotoxin into a hind footpad. Twenty-four hours later, the eyes were harvested
      for histological analysis, and the serum was collected for cytokine ELISAs. WT
      and GKO mice were also intraperitoneally injected with 1 microg of recombinant
      murine IFN-gamma (rmIFN-gamma) just after and 6 h after EIU induction, and their
      eyes and sera were evaluated 24 h after EIU induction, as above. RESULTS: The GKO
      mice had significantly more severe EIU as determined by the number of ocular
      infiltrating cells and lower serum IL-6 levels after EIU induction compared to WT
      mice. The injection of rmIFN-gamma suppressed the severity of EIU and increased
      the serum IL-6 levels in both the WT and GKO mice. CONCLUSIONS: Endogenous IFN
      gamma suppresses EIU pathogenesis. In addition, the systemic administration of
      IFN-gamma suppresses EIU. The suppressive mechanism involved is unclear but may
      relate to the production of IL-6.

PMID- 15875360
TI  - The efficacy of piperacillin/tazobactam in experimental Pseudomonas aeruginosa
      endophthalmitis: a histopathological and microbiological evaluation.
AB  - PURPOSE: To investigate the efficacy of intravitreal piperacillin/tazobactam (250
      microg/0.1 ml) in the treatment of experimental Pseudomonas aeruginosa
      endophthalmitis in rabbits. MATERIALS AND METHODS: Twenty New Zealand White
      albino rabbits were used in this study. The rabbits were divided into two groups
      (10 rabbits in each), and the right eyes were treated with 0.1 ml intravitreal
      injections of P. aeruginosa suspension (ATCC 27853, 2 x 10(4) CFU); the left eyes
      served as uninfected control and were injected with 0.1 ml of saline solution.
      The right eyes of rabbits in group 1 (n = 10) received intravitreal injection of
      250 microg piperacillin/tazobactam 24 h after intravitreal inoculation of P.
      aeruginosa. Group 2 eyes (n = 10) received no treatment and served as infected
      controls. Clinical examination of the eyes in each group was performed on the
      first, third, and sixth day after the inoculation of P. aeruginosa. After the
      last ophthalmic examination, 0.1 ml vitreous aspirates were obtained for
      microbiological analysis, and then the eyes were enucleated for histopathological
      evaluation. RESULTS: The mean clinical scores of group 1 and group 2 at the first
      day after P. aeruginosa inoculation were similar (p > 0.05). At the sixth day,
      the mean clinical score of group 1 was significantly lower when compared with
      group 2 eyes (p < 0.001). Microbiological analysis revealed that group 2 had a
      significantly more cfu/ml than group 1 (p < 0.001), and the mean
      histopathological score of group 2 was significantly higher than group 2 (p =
      0.009). CONCLUSIONS: Intravitreal application of 250 microg/0.1 ml
      piperacillin/tazobactam seems to be effective in the treatment of P. aeruginosa
      endophthalmitis in rabbits. Intravitreal piperacillin/tazobactam combination may
      be a new therapy for P. aeruginosa endophthalmitis.

PMID- 15875361
TI  - Syneretic response to incremental pressures in calf lenses.
AB  - PURPOSE: Syneretic response to pressure variation of 1 atm or more has been
      demonstrated previously in bovine and human lenses with nuclear magnetic
      resonance (NMR) relaxation measurements. This study is designed to prove that a
      similar response is observable in smaller pressure increments closer to the
      normal physiological range. METHODS: Excised calf eyes were enucleated, the
      lenses dissected out, and immersed in medium. The lenses were exposed to
      incremental pressures ranging from 1 to 3 atm. At each pressure increment, a
      series of T1-weighted and spin echo images were acquired. Each image was
      segmented into seven regions of interest and tabulated. Longitudinal (T1) and
      transverse (T2) relaxation times were calculated from numerical fits of the
      experimental values to a one-term exponential expression. RESULTS: The relaxation
      parameters were obtained from fitting the image intensities to exponential
      equations, which yielded a relaxation time T and a pre-exponential factor M. The
      relaxation times and the pre-exponential terms of both parameters displayed
      linear dependence on pressure. There was no evidence of a threshold for syneretic
      response. Both T1 and T2 relaxation times decreased with increasing pressure. The
      pre-exponential term M2 increased with pressure, whereas M1 decreased with
      pressure; however, the slope of the latter was statistically not significantly
      different from zero. CONCLUSIONS: Syneretic response to pressure in calf lenses
      as determined by NMR relaxation measurements proved to be linearly dependent on
      pressure over a wide range of hydrostatic pressures. There was no range where the
      syneretic response was absent. These two findings allow the conclusion that the
      phenomenon observed hitherto at large pressure changes in vitro could be
      operative in vivo under physiological pressure changes during accommodation.

PMID- 15875362
TI  - Localization of collagen XVIII and endostatin in the human eye.
AB  - PURPOSE: To investigate the localization of endostatin, a potent angiogenesis
      inhibitor, and its progenitor collagen XVIII in the human eye. METHODS: Twelve
      normal human eyes were investigated. Immunohistochemistry of the anterior and
      posterior eye segment was performed using a polyclonal endostatin and collagen
      XVIII antibody and a monoclonal collagen XVIII antibody. Specificity of the
      antibodies was confirmed by Western blot analysis. RESULTS: The antibody against
      collagen XVIII stained Bowman's membrane, the lens capsule, the trabecular
      meshwork, and all epithelial and endothelial basal membranes in the anterior and
      posterior eye segment. In contrast, the antibody against endostatin showed a more
      distinct staining pattern. Intense intracellular staining for endostatin was
      present in the lens epithelium and in the non-pigmented epithelium of the ciliary
      body. Extracellular presence of endostatin could be detected in the lens capsule
      and all border membranes lining the aqueous humor including the anterior surface
      of the iris. The choroid was unstained. In the retina, staining was restricted to
      the inner limiting membrane and to endothelial cells of larger vessels.
      CONCLUSIONS: Our results show that there is a ring of specifically endostatin
      expressing structures forming a "barrier" around the anterior chamber and the
      vitreous. This might physiologically prevent vessels from sprouting into these
      avascular compartments.

PMID- 15875363
TI  - Regulation of reduced-folate transporter-1 in retinal pigment epithelial cells by
      folate.
AB  - PURPOSE: Reduced-folate transporter-1 (RFT-1), a typical transport protein with
      12 membrane-spanning domains, transports reduced-folates, such as N5
      methyltetrahydrofolate (MTF), the predominant circulating form of folate. RFT-1
      is localized to the RPE apical membrane and transports folate from RPE to
      photoreceptor cells. We asked whether RFT-1 activity in RPE is altered under high
      folate conditions. MATERIALS AND METHODS: ARPE-19 cells were cultured 24, 48, or
      72 h in medium containing either 0.5 nM, 5.0 nM, or 2.26 microM MTF, and the
      activity of RFT-1 was assessed by determining the uptake of N5-MTF.
      Semiquantitative reverse transcription-polymerase chain reaction and Western blot
      analysis were used to study RFT-1 gene and protein expression. RESULTS: Cells
      treated for 72 h with 2.26 microM MTF showed a significant (40%) decrease in MTF
      uptake compared to cells exposed to 0.5 nM or 5 nM MTF. The effect of high
      concentrations of folate on RFT-1 activity was specific. Kinetic analysis showed
      that folate-induced attenuation of RFT-1 activity was associated with a decrease
      in the maximal velocity of the transporter, but no change in the substrate
      affinity. Steady-state levels of RFT-1 mRNA and protein decreased significantly
      in the presence of excess folate. CONCLUSIONS: Excess folate levels downregulate
      RFT-1 in RPE. This study represents the first molecular analysis of the
      regulation of RFT-1 by folate in RPE and reveals attenuation of the activity and
      expression of a folate transport protein under conditions of high levels of
      folate.

PMID- 15875364
TI  - In vivo assessment of postnatal murine ocular development by ultrasound
      biomicroscopy.
AB  - PURPOSE: Ultrasound biomicroscopy (UBM) can noninvasively provide anatomical
      information about mouse ocular structures. We present the quantitation of
      postnatal murine eye development using UBM. MATERIALS AND METHODS: The eyes from
      CD-1 mice were examined at 1, 2, 4, 6, and 8 weeks of postnatal development using
      40 MHz UBM. Patterns of ocular tissue growth including the lens, globe, and
      anterior chamber were calculated. RESULTS: Postnatal CD-1 lens and globe volumes
      are consistent with an exponential decay of growth during the first 8 postnatal
      weeks. Anterior chamber depth increases most sharply in the first 2 postnatal
      weeks but continues to increase up to the 8th postnatal week. Anterior segment
      angle was observed to increase from 1 to 4 weeks. CONCLUSIONS: UBM can be used to
      obtain in vivo quantitative measurements of postnatal murine ocular structures.
      Our ability to obtain ocular anatomical information will facilitate future
      assessments of mouse models of human disease.

PMID- 15875365
TI  - Development and evaluation of the specificity of a cathepsin D proximal promoter
      in the eye.
AB  - PURPOSE: Recombinant adeno-associated virus (rAAV)-mediated gene delivery has
      emerged as a valuable tool for alternative treatment of ocular diseases. Cellular
      specificity of transgene expression could be influenced by either the viral
      capsid or the choice of promoter. The use of cellular promoter, cathepsin D
      (CatD) proximal promoter, and its potential for application in rAAV-based gene
      therapy are evaluated in this study. MATERIALS AND METHODS: Different sizes of
      CatD proximal promoter fragments -769 to -1 (CD768), -366 to -1 (CD365), -253 to 
      1 (CD252), and -124 to -1 (CD123) were subcloned upstream of the green
      fluorescent protein (GFP) gene. The specificity and activity of the promoter were
      tested in vitro using human retinal pigment epithelium (RPE) cell lines (RPE51,
      D407), with the human fibroblast cell line (F2000) used as control. The promoter
      fragment that showed higher activity in RPE cells was chosen to generate rAAV
      vector based on AAV serotype 2. The ability of CatD promoter to target transgene
      expression to RPE in vivo was determined following subretinal delivery of rAAV
      particles into nonpigmented RCS/rdy+ rats. RESULTS: In vitro studies showed that
      the proximal promoter fragment CD365 targeted high GFP expression in RPE cells.
      This fragment was then used to generate the AAV.CD365.gfp construct. It was shown
      in vivo that following subretinal injection, the CD365 fragment in AAV.CD365.gfp
      directed GFP expression preferentially into RPE cells. Relatively lower level of
      GFP expression was detected in the neuroretina. In contrast, injection of control
      virus (AAV.CMV.gfp) resulted in equal levels of transduction and fluorescence
      signal intensity in both the RPE and photoreceptor cells. CONCLUSIONS: The
      results of our study demonstrate that the promoter fragment CD365 has the
      potential to target preferential gene expression in the RPE following subretinal
      injection in rAAV-mediated gene therapy.

PMID- 15875366
TI  - Effects of alpha-toxin-deficient Staphylococcus aureus on the production of
      peripheral corneal ulceration in an animal model.
AB  - PURPOSE: To examine the role of Staphylococcus aureus alpha-toxin in contact lens
      induced peripheral ulceration (CLPU). MATERIALS AND METHODS: Proteolytic enzyme,
      hyaluronidase, alpha-toxin, and beta-toxin production by S. aureus 8325-4 and its
      alpha-toxin-deficient mutant (S. aureus DU1090) were examined. Using a rabbit
      model of CLPU, animals were fitted with hydrogel contact lenses colonized by
      either S. aureus 8325-4 or the mutant strain. The clinical presentation,
      bacterial cultures, and histology of the ulceration were examined. RESULTS: Both
      strains of S. aureus produced similar levels of caseinase, gelatinase, elastase,
      hyaluronidase, and beta-toxin. S. aureus DU1090 induced weaker haemolysis of
      rabbit blood cells than S. aureus 8325-4. Ulceration in the S. aureus DU1090 eye
      was less frequent and less severe than that caused by S. aureus 8325-4.
      CONCLUSIONS: The enzyme production profile of S. aureus DU1090 was similar to the
      parent strain. S. aureus strains may produce CLPU-like lesions irrespective of
      alpha-toxin production, but severe infectious lesions are produced only in the
      presence of alpha-toxin.

PMID- 15875367
TI  - The longitudinal orthokeratology research in children (LORIC) in Hong Kong: a
      pilot study on refractive changes and myopic control.
AB  - PURPOSE: Myopia is a common ocular disorder, and progression of myopia in
      children is of increasing concern. Modern overnight orthokeratology (ortho-k) is
      effective for myopic reduction and has been claimed to be effective in slowing
      the progression of myopia (myopic control) in children, although scientific
      evidence for this has been lacking. This 2 year pilot study was conducted to
      determine whether ortho-k can effectively reduce and control myopia in children.
      METHODS: We monitored the growth of axial length (AL) and vitreous chamber depth
      (VCD) in 35 children (7-12 years of age), undergoing ortho-k treatment and
      compared the rates of change with 35 children wearing single-vision spectacles
      from an earlier study (control). For the ortho-k subjects, we also determined the
      changes in corneal curvature and the relationships with changes of refractive
      errors, AL and VCD. RESULTS: The baseline spherical equivalent refractive errors
      (SER), the AL, and VCD of the ortho-k and control subjects were not statistically
      different. All the ortho-k subjects found post-ortho-k unaided vision acceptable
      in the daytime. The residual SER at the end of the study was -0.18 +/- 0.69 D
      (dioptre) and the reduction (less myopic) in SER was 2.09 +/- 1.34 D (all values
      are mean +/- SD). At the end of 24 months, the increases in AL were 0.29 +/- 0.27
      mm and 0.54 +/- 0.27 mm for the ortho-k and control groups, respectively
      (unpaired t test; p = 0.012); the increases in VCD were 0.23 +/- 0.25 mm and 0.48
      +/- 0.26 mm for the ortho-k and control groups, respectively (p = 0.005). There
      was significant initial corneal flattening in the ortho-k group but no
      significant relationships were found between changes in corneal power and changes
      in AL and VCD. CONCLUSION: Ortho-k can have both a corrective and
      preventive/control effect in childhood myopia. However, there are substantial
      variations in changes in eye length among children and there is no way to predict
      the effect for individual subjects.

PMID- 15875368
TI  - Glucose-oxidase based self-destructing polymeric vesicles.
AB  - We have designed oxidation-responsive vesicles from synthetic amphiphilic block
      copolymers ("polymersomes") of ethylene glycol and propylene sulfide. Thioethers
      in the hydrophobic poly(propylene sulfide) block are converted into the more
      hydrophilic sulfoxides and sulfones upon exposure to an oxidative environment,
      changing the hydrophilic-lipophilic balance of the macroamphiphile and thus
      inducing its solubilization. Here we sought to explore generation of the
      oxidative environment and induction of polymersome destabilization through
      production of hydrogen peroxide by the glucose-oxidase (GOx)/glucose/oxygen
      system. We studied the encapsulation of GOx within polymersomes, its stability
      and activity, and glucose-triggered polymersome destabilization. Stimulus
      responsive polymersomes may find applications as nanocontainers in sensing
      devices and as drug delivery systems.

PMID- 15875369
TI  - Structure of microparticles in solid-stabilized emulsions.
AB  - Emulsions of oil and water stabilized by adsorbed solid particles are known as
      solid-stabilized emulsions (often referred to as Pickering emulsions). Using
      confocal microscopy, we have studied the assembly of colloidal-sized polystyrene
      particles in poly(dimethylsiloxane)-in-water solid-stabilized emulsions.
      Monodisperse polystyrene particles, when included in the emulsions at low
      concentrations, were found to form small patches with local "hexagonal" order,
      separated by other particle-free domains. Polystyrene particles with different
      sizes (1 and 4 microm) and different wettability could simultaneously segregate
      to the emulsion interface; even mixtures of hydrophobic and hydrophilic solid
      particles were found to simultaneously segregate to the same interface.

PMID- 15875370
TI  - Site-directed molecular assembly on templates structured with electron-beam
      lithography.
AB  - We describe a simple method for patterning biomolecular films on surfaces with
      high resolution. A conventional polymeric resist is structured by electron-beam
      lithography. The exposed and developed patterns are then used for the directed
      self-assembly (SA) of a first molecule from solution. Removal of the remaining
      resist allows the SA of a second species. We illustrate the potential of the
      approach by assembling on gold (Au) substrates two alkanethiols of contrasting
      terminal functionality. The patterns have dimensions from the micrometer range
      down to 40 nm and an edge resolution of 3.5 nm.

PMID- 15875371
TI  - Direct evidence for breakup of liquid fibrils via Rayleigh instabilities in model
      polymer blends in step-up experiments.
AB  - Droplet breakup in immiscible polymer blends after a sudden substantial increase
      in shear rate is studied using small-angle light scattering experiments. During
      the breakup of the fibrils, secondary streaks are visible in the scattering
      pattern, which indicate the occurrence of Rayleigh instabilities. A high
      resolution camera allows quantitative determination of the evolution of the
      wavelength of the disturbances during the disintegration process. It is shown
      that this process is time-controlled rather than strain-controlled as suggested
      by theory.

PMID- 15875372
TI  - Effect of the counterion on the rate of electron transfer in dendrimer films.
AB  - The electrochemical behavior of a film composed of a redox-active dendrimer was
      studied as a function of the type of counterion available during its reduction
      and reoxidation. The rate of permeation/migration of counterions into the film
      appeared to be the bottleneck to electron transfer through the film. Because the
      dendrimer is rather hydrophobic, increasing the hydrophobicity of the counterion
      increased the rate and extent of electron hopping within the films.

PMID- 15875373
TI  - Anomalous decrease in lamellar spacing by shear flow in a nonionic
      surfactant/water system.
AB  - We study the effects of shear flow on the structure of a lamellar phase in a
      C16E7 [hepta(oxyethylene glycol)-n-hexadecyl ether]/water system (40-55 wt % of
      C16E7) at 70 degrees C using small-angle neutron scattering in the range of shear
      rate of 10(-3)-30 s(-1). At the shear rate 0.1-1 s(-1), the repeat distance (d)
      is decreased significantly (down to about 40% of d at rest in the most
      significant case) and discontinuously with increasing shear rate. With the
      further increase in the shear rate, d increases through a sharp minimum (referred
      to as d*). Such a shear rate dependence of d is obtained for all the principal
      orientations of lamellae. As the concentration of C16E7 decreases from 55 to 40
      wt %, d increases from 6.5 to 8.5 nm at rest whereas d* remains almost constant
      (approximately equal to 5 nm). Moreover, d* is found to be almost equal to the
      thickness of bilayers obtained from the line shape analysis of small-angle X-ray
      scattering at rest. The results strongly suggest that the water layer is excluded
      by shear flow and that the lamellar phase segregates into surfactant-rich and
      water-rich regions, although these regions do not reach macroscopic size.

PMID- 15875374
TI  - Retention of structure in microemulsion polymerization: formation of nanolatices.
AB  - Polymerization of styrene-in-water microemulsions by photoinitiation using the
      initiator 2,2'-dimethoxy-2-phenyl acetophenone (DMPA) produces small nanolatices
      of the same size as the parent microemulsion (radius = 24-31 angstroms). This
      behavior is distinct from previously applied methods where significant particle
      growth accompanies the polymerization reaction. NMR measurements confirmed that
      polymerization is complete in under an hour and small-angle neutron scattering
      established the microemulsion structure before and after polymerization. The
      approach may be of more general application where retention of structure is
      sought in microemulsion-based polymer templating procedures.

PMID- 15875376
TI  - The Lotus effect: superhydrophobicity and metastability.
AB  - To learn how to mimic the Lotus effect, superhydrophobicity of a model system
      that resembles the Lotus leaf is theoretically discussed. Superhydrophobicity is
      defined by two criteria: a very high water contact angle and a very low roll-off
      angle. Since it is very difficult to calculate the latter for rough surfaces, it
      is proposed here to use the criterion of a very low wet (solid-liquid) contact
      area as a simple, approximate substitute for the roll-off angle criterion. It is
      concluded that nature employs metastable states in the heterogeneous wetting
      regime as the key to superhydrophobicity on Lotus leaves. This strategy results
      in two advantages: (a) it avoids the need for high steepness protrusions that may
      be sensitive to breakage and (b) it lowers the sensitivity of the
      superhydrophobic states to the protrusion distance.

PMID- 15875375
TI  - Absorption of water by thin, ionic films of gelatin.
AB  - This paper discusses absorption of water by thin, dry films of gelatin.
      Experiments using a wet-stamping technique were performed to characterize water
      uptake in terms of (i) equilibrium profiles of the water density inside the gel
      and (ii) the kinetics of water absorption. It was found that, in contrast to pure
      gelatin films, which absorb water approximately uniformly, films of gelatin doped
      with ionic additives have exponentially decaying equilibrium water profiles. The
      process of water absorption by both doped and undoped gels was described by a
      theoretical model based on the minimization of grand potential functional. The
      results of this model are in agreement with the experiment.

PMID- 15875378
TI  - Preparation of submicron-structured alkylsiloxane monolayers using prepatterned
      silicon substrates by laser direct writing.
AB  - A new constructive method for the preparation of laterally structured
      alkylsiloxane monolayers is demonstrated. Laser direct writing has been used to
      create oxide patterns on H-terminated Si(100) samples under ambient conditions.
      Depending on the laser power and the writing speed, oxide structures with a
      lateral resolution below 500 nm are prepared routinely. The patterned samples are
      suitable as temporary templates for the preparation of laterally structured
      octadecylsiloxane monolayers. Prior to immersion in an octadecyltrichlorosilane
      solution, however, hydration of the samples in water is essential to facilitate a
      selective coating of the oxidized areas. After coating, atomic force microscopy
      reveals the formation of octadecylsiloxane islands exclusively on top of the
      oxide lines.

PMID- 15875377
TI  - Starch-mediated shape-selective synthesis of Au nanoparticles with tunable
      longitudinal plasmon resonance.
AB  - We report the synthesis ofAu nanoparticles, with tunable longitudinal plasmon
      band and shape selectivity, mediated by starch in the presence of ultrasonic
      waves. The synthesis was carried out by reduction of HAuCl4, at various
      concentrations, using H2O2 as the reducing agent. When the reactions were carried
      out in the absence of ultrasonic waves, there was no occurrence of the
      longitudinal resonance band, while the transverse plasmon resonance band shifted
      toward a higher wavelength. Transmission electron microscopic measurements
      revealed an increase in particle sizes with increasing higher initial HAuCl4
      concentration. On the other hand, in the presence of ultrasonic waves, as the
      initial concentration of HAuCl4 was increased, while the transverse plasmon
      resonance band remained the same, the longitudinal plasmon resonance band
      increasingly shifted toward a higher wavelength. Transmission electron
      microscopic measurements revealed the change in shape from spherical to
      triangular to hexagonal particles with increasing initial HAuC14 concentration.
      We also report that the starch-stabilized nanoparticles could be precipitated
      from the solution by a starch digesting enzyme which also binds with the
      particles resulting in its precipitation.

PMID- 15875379
TI  - Structure evaluation and highly enhanced luminescence of Dy3+ -doped ZnO
      nanocrystals by Li+ doping via combustion method.
AB  - In this paper, Dy3+ -doped ZnO nanocrystals have been synthesized via a simple
      combustion method. The as-prepared cuboid-like ZnO nanocrystals appear to be
      single hexagonal crystalline phase with an average diameter of 20 nm. The
      characteristic luminescence of doped Dy3+ ions has been evaluated, and the highly
      enhanced photoluminescence of Dy3+ ions can be obtained by Li+ doping.

PMID- 15875380
TI  - Probing the pore wall structure of nanoporous carbons using adsorption.
AB  - Hitherto, adsorption has been traditionally used to study only the porous
      structure in disordered materials, while the structure of the solid phase
      skeleton has been probed by crystallographic methods such as X-ray diffraction.
      Here we show that for carbons density functional theory, suitably adapted to
      consider heterogeneity of the pore walls, can be reliably used to probe features
      of the solid structure hitherto accessibly only approximately even by
      crystallographic methods. We investigate a range of carbons and determine pore
      wall thickness distributions using argon adsorption, with results corroborated by
      X-ray diffraction.

PMID- 15875381
TI  - Flocculation of microgel particles with sodium chloride and sodium polystyrene
      sulfonate as a function of temperature.
AB  - The flocculation behavior of poly(N-isopropylacrylamide) (PNIPAM) microgel
      particles, containing surface sulfate groups, has been studied as a function of
      sodium chloride [NaCl] concentration, between 0.1 and 800 mM NaCl and over the
      temperature range 25-60 degrees C. The critical flocculation temperature (CFT) of
      the particles was determined as a function of NaCl concentration. Three regions
      of NaCl concentration were established. First, at very low values of [NaCl] (<
      approximately 25 mM), no CFT value could be determined; this implies that the
      interparticle electrostatic repulsion is sufficient to prevent any flocculation
      occurring. This remains the case even at temperatures well in excess of the lower
      critical solution temperature for PNIPAM in solution, where the particles are
      essentially deswollen. Second, at intermediate [NaCl] (approximately 25-100 mM),
      the CFT decreased strongly with increasing [NaCl]. In this region, the
      electostatic forces are weakened sufficiently for the van der Waals forces to
      cause flocculation. Third, at higher [NaCl] (> approximately 100 mM), the
      electrostatic repulsion is screened out, and the CFT decreases linearly with
      [NaCl]. The reason for this decrease is the fact that aqueous solutions of NaCl
      become increasingly poorer solvent environments for PNIPAM with increasing
      [NaCl]. These trends are apparent also in the values determined for the
      hydrodynamic size of the stable PNIPAM particles as a function of [NaCl] and
      temperature. It is shown that the flocculation of the PNIPAM particles is
      consistent with a weak, reversible flocculation model. This is apparent, for
      example, from the fractal dimensions of the flocs (approximately 2.0), determined
      from the power law used to fit the time evolution of the hydrodynamic size of the
      flocs, and also from the estimated depth of the mimimum in the interparticle pair
      potential, based on the critical size of the primary particles where flocculation
      just begins to occur. The effect of adding sodium poly(styrene sulfonate) [PSS]
      to the PNIPAM dispersions, in the absence of NaCl, was also investigated. The
      minimum amount of PSS required to induce flocculation was found to decrease with
      increasing temperature.

PMID- 15875382
TI  - Influence of metalation on the morphologies of poly(ethylene oxide)-block-poly(4
      vinylpyridine) block copolymer micelles.
AB  - Micellization of a poly(ethylene oxide)-block-poly(4-vinylpyridine) (PEO45-b
      P4VP28) copolymer in water during metalation (incorporation of gold compounds and
      gold nanoparticle formation) with three types of gold compounds, NaAuCl4, HAuCl4,
      and AuCl3, was studied using dynamic light scattering (DLS) and transmission
      electron microscopy (TEM). The transformations of the PEO45-b-P4VP28 block
      copolymer micelles in water were found to depend on a number of parameters
      including the thermal history of the as-prepared block copolymer, the type of the
      metal compound, and the metal loading. For the HAuCl4-filled PE045-b-P4VP28
      micelles, the subsequent reduction with hydrazine hydrate results in a
      significant fraction of rodlike micelles, suggesting that slow nucleation
      (confirmed by the formation of the large gold nanoparticles) and facilitated
      migration of gold ions yields the ideal conditions for sphere-to-rod micellar
      transition.

PMID- 15875383
TI  - Optical spectroscopic and TEM studies of catanionic micelles of CTAB/SDS and
      their interaction with a NSAID.
AB  - If a vesicle is a better model of a membrane in the context of the hydrophobic
      effect, then from the charge distribution point of view, a catanionic micelle is
      a closer model to a biomembrane. We have prepared and characterized two different
      types of catanionic micelles of sodium dodecyl sulfate (SDS) and cetyl N,N,N
      trimethylammonium bromide (CTAB) having different surface charge ratios using
      optical spectroscopy and transmission electron microscopy. The average size of
      both types of mixed micelles was found to be much larger than that of micelles
      containing uniformly charged headgroups. Catanionic micelles containing higher
      concentrations of positively charged headgroups (CTAB) are larger in size, less
      compact, and more polar compared to the micelles containing higher concentrations
      of negatively charged headgroups (SDS). We have used these catanionic micelles as
      membrane mimetic systems to understand the interaction of piroxicam, a
      nonsteroidal anti-inflammatory drug (NSAID) of the oxicam group, with
      biomembranes. In continuation of our work on membrane mimetic systems, we have
      used spectral properties of the drug itself to understand the effect of the
      presence of mixed charges on the micellar surface in guiding the interaction of
      catanionic micelles with piroxicam. Our earlier studies of the interaction of
      piroxicam with micelles having uniform surface charges have shown that the charge
      on the micellar surface not only dictates which prototropic form of the drug will
      be incorporated in the micelles but also induces a switch-over between different
      prototropic forms of piroxicam. The equilibrium of this switch-over is extremely
      sensitive to the environment. In this study, we demonstrate how even small
      changes in the electrostatic forces obtained by doping the uniformly charged
      surface of the micelles with oppositely charged headgroups (as in catanionic
      micelles) are capable of fine-tuning this equilibrium. This implies that the
      surface charge of biomembranes, which are quite diverse in vivo, might play a
      significant role in selecting a particular form of the drug to be presented to
      its targets.

PMID- 15875384
TI  - Microemulsification of triglyceride sebum and the role of interfacial structure
      on bicontinuous phase behavior.
AB  - A unique triblock surfactant is reported that allows for the efficient
      microemulsification of triglycerides. Unlike the results of all previous efforts,
      these triglyceride microemulsions can be formed without the use of cosurfactants
      or dilution with co-oils and follow the classical patterns of surfactant phase
      behavior exhibited by mixtures of water, alkane oils, and nonionic oligoethylene
      glycol surfactants, i.e., progression from oil/water emulsions to one-phase
      microemulsions to water/oil emulsions with increasing temperature. Lamellar
      phases that usually dominate the aqueous phase behavior of
      surfactant/triglyceride mixtures are suppressed, allowing for the formation of
      single-phase microemulsions containing equal amounts of triglyceride and water.
      These isotropic and low-viscous fluids are particularly useful for cleansing and
      delivery of functional ingredients in skin care products. The effects of mixing a
      variety of typical skin care ingredients and components of sebum (skin oil) were
      also explored. Fatty acids significantly reduce the average microemulsion
      temperature, while other ingredients and oils, which do not partition at the
      oil/water interface, have less impact on the phase behavior. In all cases, one
      phase microemulsions containing equal amounts of oil and water can be formed even
      at high additive concentrations. Indeed, partial replacement oftriglyceride with
      any of the additives examined consistently reduced the amount of surfactant
      necessary to form single-phase microemulsions. However, the greatest boost in
      surfactant efficiency was found with the addition of medium molecular weight
      amphiphilic block copolymers.

PMID- 15875385
TI  - Shear-induced phase separation in solutions of wormlike micelles.
AB  - Polymer solutions in the vicinity of the theta-point are known to undergo shear
      induced turbidity or phase separation. The present study shows that a similar
      phenomenon also occurs for certain wormlike micellar solutions. Wormlike micelles
      are the self-assembled counterparts of polymers and are characterized by their
      ability to reversibly break and recombine. In the system of interest, the
      micelles are formed by the cationic surfactant erucyl
      bis(hydroxyethyl)methylammonium chloride (EHAC), in conjunction with a salt such
      as sodium chloride (NaCl) or sodium salicylate (NaSal). Micellar samples that
      become turbid under shear show evidence of critical concentration fluctuations
      and may contain predominantly branched micelles. The shear-induced turbidity in
      these samples correlates with the appearance of flow-dichroism in rheooptic
      experiments and with an increase in low-q scattering in small-angle light
      scattering under flow (flow-SALS) experiments. The characteristic "butterfly"
      pattern, with enhanced scattering in the flow direction and a dark streak
      perpendicular to the flow direction, is typically observed in flow-SALS. The
      results suggest that the turbidity is due to a shear-induced growth of
      concentration fluctuations, which in turn manifests as large anisotropic domains,
      typically oriented along the vorticity axis.

PMID- 15875386
TI  - Design of double emulsions by osmotic pressure tailoring.
AB  - A method was developed allowing in situ adjustment of water-in-oil-in-water
      double emulsion (W/O/W) morphologies by tailoring the osmotic pressure of the
      water phases. The control of internal droplet size is achieved by altering the
      chemical potential of the external and internal water phases by dissolving
      neutral linear polysaccharides of suitable molecular weights. As a consequence of
      the different chemical potentials in the two aqueous phases, transport of water
      takes place modifying the initial morphology of the double emulsion. Self
      diffusion 1H nuclear magnetic resonance (1H NMR) was used to assess transport
      mechanisms of water in oil, while a numerical model was developed to predict the
      swelling/shrinking behavior of W/O/W double emulsions. The model was based on a
      two-step procedure in which the equilibrium size of a single internal water
      droplet was first predicted and then the results of the single droplet were
      extended to the entire double emulsion. The prediction of the equilibrium size of
      an internal droplet was derived by the equalization of the Laplace pressure with
      the osmotic pressure difference of the two aqueous phases, as modeled by mean
      field theory. The double emulsion equilibrium morphologies were then predicted by
      upscaling the results of a single drop to the droplet size distribution of the
      internal W/O emulsion. Good agreement was found between the theoretical
      predictions and the measurement of double emulsion droplet size distribution.
      Therefore, the present model constitutes a valuable tool for in situ control of
      double emulsion morphology and enables new possible applications of these
      colloidal systems.

PMID- 15875387
TI  - Structural and rheological properties of hydrophobically modified polysaccharide
      associative networks.
AB  - The phase behavior of hydrophobically modified chitosans (HMCs) in aqueous
      solution has been investigated using scattering and rheology experiments. We
      observed four regions on the phase diagram of the associative polymer: (i) a
      supernatant phase (unimers phase) at low polymer concentration; (ii) a dilute
      solution of intermolecularly bridged flowerlike micelles at intermediate
      concentration; (iii) an associative gel phase at high polymer content; and (iv) a
      phase separation. In the present paper, we discuss the structural and dynamical
      properties of the HMC associative networks (c > c*) at a fixed hydrophobic degree
      of substitution of 2% and fixed alkyl side chains (stickers) length C8 (domains
      iii and iv of the phase diagram). As the polymer concentration is increasing, a
      connecting network is formed from the percolation of bridges between micellar
      aggregates. In this regime, small-angle neutron scattering and light scattering
      measurements show that -50-nm flower aggregates are acting like junction points
      in the network. The effect of the concentration, the stress, and the shear on the
      structure of the network is discussed. In particular, we observe bridge-to-loop
      transitions and then the formation of microgels or a low-connected network under
      shear. Therefore, our results are compared to recent theoretical models and to
      the results reported for telechelic systems.

PMID- 15875388
TI  - Neutron reflectivity and external reflection FTIR studies of DL-aspartic acid
      crystallization beneath nylon 6 spread films.
AB  - The crystallization of DL-aspartic acid beneath nylon 6 spread films has been
      studied for 150% supersaturated systems using neutron reflectivity and external
      reflection FTIR. The neutron reflectivity data showed the gradual incorporation
      of DL-aspartic acid within a nylon 6 spread film layer over a period of 6-8 h,
      culminating in over 50 vol % of the "film" layer comprising DL-aspartic acid.
      Accumulation of further DL-aspartic acid material to produce
      microscopic/macroscopic surface crystals occurred, but on a more limited scale,
      resulting in approximately 1-5% surface coverage of crystals over the same
      period. External reflection FTIR studies revealed very weak bands attributable to
      DL-aspartic acid in surface regions devoid of visible crystals, in agreement with
      the neutron reflectivity studies. In regions with visible crystals, much larger
      and sharper DL-aspartic acid bands were seen. Changes in the intensity of the
      nylon 6 NH stretch band were often observed during the visible crystallization
      and dissolution of DL-aspartic acid and were consistent with the reversible
      accumulation of nylon 6 around the growing crystals.

PMID- 15875389
TI  - Preparation and tribological studies of C60 thin film chemisorbed on a functional
      polymer surface.
AB  - A novel self-assembled C60 film was prepared by chemical adsorption of C60
      molecules onto an amino-group-containing polyethyleneimine-coated silicon
      substrate surface. The contact angle of distilled water on the C60 film was
      measured, the thickness was determined by means of ellipsometric analysis, and
      the morphology was observed with an atomic force microscope. The tribological
      properties of the films were investigated as well. It was found that the C60 thin
      film had a contact angle of about 72 degrees and thickness of 1.8 nm and
      exhibited a surface domain microstructure composed of fullerene clusters. Due to
      the hydrophobicity and low surface energy, the C60 film possessed good adhesive
      resistance and had an adhesive force of about 7.1 nN, which was about an order of
      magnitude lower than that of the silicon substrate surface. Moreover, the C60
      film showed good friction reduction, load-carrying capacity, and antiwear
      ability, which were attributed to the higher mechanical stiffness and elastic
      modulus of C60 molecules. Besides, the friction coefficient decreased with
      increasing sliding velocity and normal loads, due to the rolling effect of the
      physisorbed C60 molecules.

PMID- 15875390
TI  - Preparation and characterization of polyion-complexed Langmuir-Blodgett films
      containing an NLO chromophore.
AB  - Polyion complexes formed by monolayers of quaternary ammonium amphiphiles
      containing the 4-nitro-4'-alkoxy azobenzene chromophore spread at the surface of
      aqueous solutions of a number of anionic polyelectrolytes were investigated. In
      general, pi-A isotherms were found to depend on the nature of the polyion present
      in the subphase, with monolayers of complexes involving polycarboxylates tending
      to exhibit larger limiting areas than those formed with polysulfonates or
      polysulfates. Monolayers of the polyion complexes can be transferred to
      hydrophilic solid substrates to yield Z-type LB films, although some peeling off
      for more than 10 layers is an impediment. X-ray reflectivity measurements
      indicate that relatively smooth and uniform films are obtained up to about 10
      layers. Average layer thicknesses are, however, significantly smaller than
      extended molecular lengths, implying that the amphiphiles are strongly inclined
      from the surface normal. Polarized FT-IR measurements also indicate poor
      molecular orientation perpendicular to the surface. Preliminary SHG measurements
      for LB films of two systems, 12Q/CMC-Na and 12Q/PAA, confirm the presence of
      noncentrosymmetric out-of-plane chromophore ordering. Stable signals are observed
      for elevated temperatures up to 130 degrees C and for a period of 4 months at
      room temperature. To the best of our knowledge, this represents the first report
      of stable SHG in LB films of polyion complexes.

PMID- 15875391
TI  - Preparing contamination-free mica substrates for surface characterization, force
      measurements, and imaging.
AB  - Due to its perfect cleavage that provides large areas of molecularly smooth,
      chemically inert surfaces, mica is the most commonly used natural substrate in
      measurements with the surface forces apparatus (SFA), in atomic force microscopy
      (AFM), and in many adsorption studies. However, preparing mica surfaces that are
      truly clean is not easy since mica is a high-energy surface that readily adsorbs
      water, organic contaminants, and gases from the atmosphere. Mica can also become
      charged on cleaving, which makes it prone to picking up oppositely charged
      particles or mica flakes from the surroundings. High refractive index particles,
      such as metals, will adhere to mica through van der Waals forces. Recent articles
      have demonstrated that particle contamination is obtained when inappropriate
      cutting and handling procedures for the mica are used. In this paper, we show
      that both particle and other critical contamination is easy to detect and provide
      proper steps to take during the sample preparation process.

PMID- 15875392
TI  - Chemisorption and reaction characteristics of methyl radicals on Cu(110).
AB  - Methyl radicals are generated by pyrolysis of azomethane, and the condition for
      achieving neat adsorption on Cu(110) is described for studying their
      chemisorption and reaction characteristics. The radical-surface system is
      examined by X-ray photoemission spectroscopy, ultraviolet photoemission
      spectroscopy, temperature-programmed desorption, low-energy electron diffraction
      (LEED), and high-resolution electron energy loss spectroscopy under ultrahigh
      vacuum conditions. It is observed that a small fraction of impinging CH3 radicals
      decompose into methylene possibly on surface defect sites. This type of CH2
      radical has no apparent effect on CH3(ads) surface chemistry initiated by
      dehydrogenation to form active CH2(ads) followed by chain reactions to yield high
      mass alkyl products. All thermal desorption products, such as H2, CH4, C2H4,
      C2H6, and C3H6, are detected with a single desorption peak near 475 K. The
      product yields increase with surface coverage until saturation corresponding to
      0.50 monolayer of CH3(ads). The mass distribution is, however, invariant with
      initial CH3(ads) coverage, and all desorbed species exhibit first-order reaction
      kinetics. LEED measurement reveals a c(2 x 2) adsorbate structure independent of
      the amount of gaseous exposure. This strongly suggests that the radicals
      aggregate into close-packed two-dimensional islands at any exposure. The
      islanding behavior can be correlated with the reaction kinetics and is deemed to
      be essential for the chain propagation reactions. Some relevant aspects of the
      CH3/Cu(111) system are also presented. The new results are compared with those of
      prior studies employing methyl halides as radical sources. Major differences are
      found in the product distribution and desorption kinetics, and these are
      attributed to the influence of surface halogen atoms present in those earlier
      investigations.

PMID- 15875393
TI  - Surfactant templated sulfonic acid functionalized silica microspheres as new
      efficient ion exchangers and electrode modifiers.
AB  - Porous sulfonic acid functionalized silica spheres have been prepared by
      oxidation ofthiol-functionalized mesoporous silica samples obtained by co
      condensation of (mercaptopropyl)trimethoxysilane and tetraethoxysilane in the
      presence ofcetyltrimethylammonium as a template. The physicochemical
      characteristics of the resulting ion exchangers have been analyzed by various
      techniques and discussed with respect to the amount of functional groups in the
      materials. Their ion exchange behavior was then studied from batch experiments
      (determination of cation exchange capacities) and by electrochemistry at carbon
      paste electrodes modified with these solids. In particular, ion exchange
      voltammetry applied to two model electroactive cations, Cu2+ and Ru(NH3)6(3+),
      has pointed out the key role played by the content of organofunctional groups in
      the materials (which strongly affects their structure and porosity) on their
      performance as electrode modifiers for preconcentration of target analytes prior
      to electrochemical detection.

PMID- 15875394
TI  - H2S-induced reorganization of mixed monolayer of carboxylic derivatives on silver
      surface.
AB  - The structure of self-assembled monolayers ofp-terphenyl-4-carboxylic acid and
      the mixed monolayers of this acid with n-hexadecanoic acid on silver surface were
      studied by reflection-IR spectroscopy, near-edge X-ray absorption fine structure
      (NEXAFS) measurement, X-ray photoemission electron microscopy (X-PEEM), and
      atomic force microscopy. Exposure of the p-terphenyl-4-carboxylate monolayer to
      H2S vapor resulted in reorganization of the film structure into clusters of the
      corresponding free acids, in tens of nanometer dimension. Exposure of the mixed
      monolayer to H2S resulted in reorganization of the mixed monolayer film into
      phase-separated clusters of respective component molecules. The saturated
      aliphatic acid formed clusters of submicrometer size, whereas the p-terphenyl-4
      carboxylic acid formed clusters of tens of nanometer size, presumably due to
      different surface mobility and/or intermolecular interaction of the two types of
      molecule. Restoration of the monolayer film from the clusters, driven by the
      reaction between the free acid molecules and the basic surface sites, proceeded
      at different speeds for the two types of molecules. The saturated acid monolayer
      was restored much faster than the p-terphenyl-4-carboxylic acid monolayer. A
      domain-separated monolayer in several micrometers scale was obtained. The process
      was imaged by tapping mode atomic force microscopy.

PMID- 15875395
TI  - Dynamic surface tension of polyelectrolyte/surfactant systems with opposite
      charges: two states for the surfactant at the interface.
AB  - The molecular reorientation model of Fainerman et al. is conceptually adapted to
      explain the dynamic surface tension behavior in polyelectrolyte/surfactant
      systems with opposite charges. The equilibrium surface tension curves and the
      adsorption dynamics may be explained by assuming that there are two different
      states for surfactant molecules at the interface. One of these states corresponds
      to the adsorption of the surfactant as monomers, and the other to the formation
      of a mixed complex at the surface. The model also explains the plateaus that
      appear in the dynamic surface tension curves and gives a picture of the
      adsorption process.

PMID- 15875396
TI  - Retention of Co(II), Ni(II), and Cu(II) on a purified brown humic acid. Modeling
      and characterization of the sorption process.
AB  - Brown humic acids (BHAs) constitute the most polar and soluble fraction of humic
      acids. Their colloidal character and their high number of functional surface
      groups justify their higher reactivity as against metallic cations with respect
      to other humic fractions (i.e., gray humic acids and humins). The aim of this
      work is to study the retention mechanisms of Cu(II), Ni(II), and Co(II) on a BHA
      by means of a proper combination of physical and chemical techniques: sorption
      isotherms, mathematical modeling of these isotherms, molecular modeling, FTIR,
      and N2 (77 K) and CO2 (273 K) adsorption. Electrostatic retention for the three
      cations is an important mechanism at very low concentrations. Its magnitude is
      higher than that of the specific retention in the initial stages of the retention
      but it decreases progressively with respect to the former as the initial metal
      concentration increases. The BHA surface area varies with the amount of retained
      metal. When the initial amount of added metal is low (n0 < 80 mmol kg(-1)), the
      cations form 2:1 complexes, which are energetically favored due to the chelate
      effect. To obtain this coordination, the BHA slightly modifies its conformation
      by decreasing its area. When the initial amount of added metal is sufficiently
      high to occupy most of the surface functional groups (n0 > 1280 mmol kg(-1)), the
      cations are heterogeneously retained over the whole surface, thus preventing the
      available groups at low n0 from giving place to the 2:1 complexes due to the fact
      that they are already occupied.

PMID- 15875397
TI  - Quartz crystal microbalance (QCM) in high-pressure carbon dioxide (CO2):
      experimental aspects of QCM theory and CO2 adsorption.
AB  - The quartz crystal microbalance (QCM) technique has been developed into a
      powerful tool for the study of solid-fluid interfaces. This study focuses on the
      applications of QCM in high-pressure carbon dioxide (CO2) systems. Frequency
      responses of six QCM crystals with different electrode materials (silver or gold)
      and roughness values were determined in helium, nitrogen, and carbon dioxide at
      35-40 degrees C and at elevated pressures up to 3200 psi. The goal is to
      experimentally examine the applicability of the traditional QCM theory in high
      pressure systems and determine the adsorption of CO2 on the metal surfaces. A new
      QCM calculation approach was formulated to consider the surface roughness
      contribution to the frequency shift. It was found that the frequency-roughness
      correlation factor, Cr, in the new model was critical to the accurate calculation
      of mass changes on the crystal surface. Experiments and calculations demonstrated
      that the adsorption (or condensation) of gaseous and supercritical CO2 onto the
      silver and gold surfaces was as high as 3.6 microg cm(-2) at 40 degrees C when
      the CO2 densities are lower than 0.85 g cm(-3). The utilization of QCM crystals
      with different roughness in determining the adsorption of CO2 is also discussed.

PMID- 15875398
TI  - Photooxidation of a mustard gas simulant over TiO2-SiO2 mixed-oxide
      photocatalyst: site poisoning by oxidation products and reactivation.
AB  - The photooxidation of 2-chloroethyl ethyl sulfide (2-CEES), a simulant for
      mustard gas, was studied using transmission IR spectroscopy on a mixed-oxide TiO2
      SiO2 photocatalyst. Ultraviolet irradiation in the photon energy range from 2.1
      to 5 eV was employed at a catalyst temperature of 200 K. Rapid photooxidation was
      observed by the loss of infrared intensity in the v(CHx) stretching region, and
      concomitant infrared features of adsorbed oxidation products were observed to
      develop. The oxidation products, captured on the photocatalyst at 200 K, were
      found to block 2-CEES readsorption. Upon heating the poisoned photocatalyst to
      about 300 K, infrared measurements indicate that the adsorbed CO2 oxidation
      product was desorbed. The capability for full readsorption of 2-CEES was achieved
      upon heating the poisoned photocatalyst to 397 K, and continued rapid
      photooxidation of the 2-CEES was then possible at about 1/3 the rate found for
      the fresh catalyst. Thus thermal treatment at 397 K of oxidation-product-poisoned
      TiO2-SiO2 material is able to partially restore the TiO2-SiO2 photooxidation
      activity.

PMID- 15875399
TI  - The Hofmeister anion effect and the growth of polyelectrolyte multilayers.
AB  - The influence of a variety of counteranions on the properties of polyelectrolyte
      multilayers deposited by layer-by-layer technique is studied by using
      ellipsometry and AFM. We found out that in thin dry multilayers (20-90 nm)
      ofpoly(4-styrenesulfonate) (PSS) and poly(diallyldimethylammonium) (PDADMA), the
      thickness follows reasonably well the position of the counteranion in the
      Hofmeister series. The polyelectrolyte-counteranion interaction is studied by
      means of viscosity measurements of semidilute solutions of PDADMA in the presence
      of different anions. The dynamic viscosities follow the Hofmeister series of
      anions and correlate with the thickness of multilayers. Two parameters describing
      the interaction of ions with water, the Jones-Dole viscosity B coefficient and
      the hydration entropy, are used to explain the anion effect on the developing
      multilayer thickness. Reasonably smooth and monotonic functional dependence is
      observed between the layer thickness and these two parameters.

PMID- 15875400
TI  - Electrostatic force microscopy analysis of lipid miscibility in two-component
      monolayers.
AB  - Electrostatic force microscopy (EFM) was used to assess lipid miscibility and
      phase behavior in two-component Langmuir-Blodgett (LB) monolayers composed of
      cationic dioctadecyldimethylammonium bromide (DOMA) and nonionic methyl stearate
      (SME) lipids. The surface potential measurements were calibrated by applying
      known bias voltages to the sample during several line scans, thus creating
      surface potential "scale bars" on the images from which it was determined that
      circular domains were 50 mV more positive than the surrounding phase. As the
      spatially averaged surface potential of DOMA was over 400 mV more positive than
      that of SME, this 50-mV surface potential difference is too low to correspond to
      lipid phase separation (immiscibility) in the two-component film. Rather, the
      surface potential contrast was attributed to an increased packing density and a
      more orthogonal orientation of lipids in the domains resulting in a greater
      contribution of dipoles to the measured (normal) surface potential. Monolayers
      prepared by sequentially spreading the two lipids resulted in irregular domains
      that were 50-450 mV more positive than the surrounding phase, representing
      varying degrees of lipid mixing, restricted by two-dimensional diffusion at the
      interface. Fluorescent images of monolayers stained with negatively charged dye
      supported the EFM miscibility prediction and assignment of surface potential.
      These results demonstrate a new approach using EFM to quantitatively measure
      surface potential in order to assess the lateral distribution of components in
      thin films as well as predict adsorption patterns to heterogeneous interfaces.

PMID- 15875401
TI  - Photophysics on surfaces: determination of absolute fluorescence quantum yields
      from reflectance spectra.
AB  - A method for the calculation of absolute fluorescence quantum yields for dyes
      attached to solid particles based on reflectance measurements is reported. The
      same procedure allows calculation of true reflectance spectra (free of
      fluorescence) for highly fluorescent materials as well. Samples ofcresyl violet
      were immobilized by adsorption on microgranular cellulose in the concentration
      range 4.5 x 10(-9) to 3.8 x 10(-6) mol g(-1). Diffuse and total reflectance
      spectra were recorded with and without insertion of an optical absorption filter
      between the output of the integrating sphere of a reflectance spectrometer and
      the photodetector in order to block fluorescence partially. From these data, the
      relative emission spectrum of the dye, the filter transmission spectrum, and the
      detector sensitivity, true reflectances and absolute fluorescence quantum yields
      were recovered. Observed fluorescence quantum yields, affected by dye aggregation
      and inner filter effects, were concentration and wavelength dependent, ranging
      approximately between 0.1 and 0.6. The analysis of remission function spectra
      showed that dye aggregation is negligible up to a concentration of 1.41 x 10(-7)
      mol g(-1). Fluorescence data were corrected for reemission and reabsorption using
      a suitable model [Lagorio, M. G.; Dicelio, L. E.; Litter, M. I.; San Roman, E. J.
      Chem. Soc., Faraday Trans. 1998, 94, 419]. Application of this model to samples
      showing no aggregation yielded a wavelength-independent true fluorescence quantum
      yield of 0.60 +/- 0.05, similar to values found in solution. The usage of cresyl
      violet as a reference for the evaluation of fluorescence quantum yields for
      weakly fluorescing samples in the solid phase is discussed.

PMID- 15875402
TI  - Nanoscale high-frequency contact mechanics using an AFM tip and a quartz crystal
      resonator.
AB  - The transmission of high-frequency shear stress through a microscopic contact
      between an AFM tip and an oscillating quartz plate was measured as a function of
      vertical pressure, amplitude, and surface properties by monitoring the MHz
      component of the tip's deflection. For dry surfaces, the transmission of shear
      stress is proportional to the vertical load across the contact. This provides a
      measure of the forces of adhesion between the substrate and the tip. When
      stretching soft polymeric fibers created by pulling on the surface of a pressure
      sensitive adhesive, the transmitted shear stress decreased linearly with
      extension over the entire range of pulling. This contrasts with the static
      adhesive force, which remained about constant until it discontinuously dropped at
      the point of rupture.

PMID- 15875403
TI  - Methods for generating protein molecular ions in ToF-SIMS.
AB  - One of the greatest challenges in mass spectrometry lies in the generation and
      detection of molecular ions that can be used to directly identify the protein
      from the molecular weight of the molecular ion. Typically, proteins are large (MW
      > 1000), nonvolatile, and/or thermally labile, but the vaporization process
      produced by many mass spectrometry techniques including time-of-flight secondary
      ion mass spectrometry (ToF-SIMS) is inherently limited to generating ions from
      smaller compounds or fragments of the parent molecule, making the identification
      of proteins complex. The application of specific molecules to aid in the
      generation of high molecular weight ions in ToF-SIMS has been recognized for some
      time. In this study we have developed a matrix-SAM substrate preparation
      technique based on the self-assembly of a matrix-like molecule, mercaptonicotinic
      acid (MNA), on gold. We then compare this substrate with two existing ToF-SIMS
      sample preparation techniques, cationized alkane thiol and matrix-enhanced SIMS
      (MESIMS). The results of this study illustrate that while there is a range of
      methods that can be used to improve the molecular ion yield of proteins in ToF
      SIMS, their efficacy and reproducibility vary considerably and crucially are
      linked to the sample preparation and/or protein application methods used.
      Critically, the MNA modified substrate was able to simultaneously induce
      molecular ions for each protein present in a multicomponent solution, suggesting
      that this sample preparation technique may have future application in proteomics
      and DNA analysis.

PMID- 15875404
TI  - A streptavidin linker layer that functions after drying.
AB  - The ability of streptavidin (SA) to simultaneously bind four biotins is often
      used in linker layers, where a biotinylated molecule is linked to a biotin
      functionalized surface via SA. For biosensor and array applications, it is
      desirable that the SA linker layer be stable to drying and rehydration. In this
      study it was observed that a significant decrease in binding capacity of a SA
      layer occurred when that layer was dried. For this study a SA linker layer was
      constructed by binding SA to a biotin-containing alkylthiolate monolayer
      (BAT/OEG) self-assembled onto gold. Its stability after drying was investigated
      using surface plasmon resonance (SPR). Approximately a quarter of the SA layer
      was removed from the BAT/OEG surface upon drying and rehydration, suggesting
      disruption of SA-biotin binding when dry. This resulted in the dried SA layer
      losing approximately 40% of its biotinylated ferritin (BF) binding capacity.
      Coating the layer with trehalose before drying was found to inhibit the loss of
      SA from the BAT/OEG surface. SPR showed that the trehalose-protected SA linker
      layer retained approximately 91% of its original BF binding capacity after drying
      and rehydration. Atomic force microscopy, which was used to image individual
      surface-bound SA and BF molecules, qualitatively confirmed these observations.

PMID- 15875405
TI  - Free-standing nanogold membranes as scaffolds for enzyme immobilization.
AB  - We demonstrate herein the formation of a free-standing gold nanoparticle membrane
      and its use in the immobilization of the enzyme, pepsin. The nanogold membrane is
      synthesized by the spontaneous reduction of aqueous chloroaurate ions at the
      liquid-liquid interface by the bifunctional molecule bis(2-(4-aminophenoxy)ethyl)
      ether (DAEE) taken in chloroform. This process results in the formation of a
      robust, malleable free-standing nanogold membrane consisting of gold
      nanoparticles embedded in a polymeric background. Recognizing that gold
      nanoparticles are excellent candidates for immobilization of enzymes, we have
      immobilized pepsin on the nanogold membrane, leading to a new class of
      biocatalyst. A highlight of the new pepsin-nanogold biocatalyst is the ease with
      which separation from the reaction medium may be achieved. The catalytic activity
      of pepsin in the bioconjugate was comparable to that of the free enzyme in
      solution. The pepsin-nanogold membrane bioconjugate material exhibited excellent
      biocatalytic activity over 10 successive reuse cycles as well as enhanced pH,
      temperature, and temporal stability.

PMID- 15875406
TI  - Cross-linking the protein precursor of marine mussel adhesives: bulk measurements
      and reagents for curing.
AB  - Marine mussels affix themselves to surfaces by use of a highly cross-linked,
      protein-based adhesive. Metal levels (e.g., Fe, Zn, Cu, Mn) of the cured glue are
      significantly concentrated relative to surrounding waters. Specific details on
      the reagents used by mussels to induce protein cross-linking are not known at
      this time. To provide insight on the cross-linking agents and reactions taking
      place while curing mussel glues, we performed a study in which various compounds
      were tested for the ability to bring about protein curing. A precursor to
      adhesion, with proteins containing the unusual amino acid 3,4
      dihydroxyphenylalanine, was extracted from mussel feet. Potential cross-linking
      agents were mixed with this gelatinous pellet. The compressibility and shear
      properties of the resulting material were investigated by use of a penetration
      test. The reagents examined included simple metal ions (e.g., Na+, Zn2+),
      oxidizing transition metals (e.g., Fe3+, Cr2O7(2-)), nonmetallic oxidants (e.g.,
      H2O2,IO4-), and oxidizing enzymes (e.g., tyrosinase). We found that protein
      curing was brought about by simple oxidants and transition metal ions. The
      results show that optimal curing occurs when the reagent is an oxidizing metal
      ion (e.g., MnO4-, Fe3+). We conclude that marine mussels are likely to employ
      Mn3+ and Fe3+ for protein cross-linking and adhesive synthesis.

PMID- 15875407
TI  - Orientation of peptides in aqueous monolayer films. Infrared reflection
      absorption spectroscopy studies of a synthetic amphipathic beta-sheet.
AB  - Infrared reflection-absorption spectroscopy (IRRAS) intensities of the Amide I
      vibration are used to develop a quantitative approach for determining the Euler
      angles that describe the orientation of protein beta-sheets in aqueous monolayer
      films. A synthetic amphipathic peptide, Val-Glu-Val-Orn-Val-Glu-Val-Orn-Val-Glu
      Val-Orn-Val-OH is used as a test case. The pattern of Amide I frequencies
      suggests that the molecule is organized as an antiparallel beta-sheet at the
      air/water interface. The model used to simulate the Amide I intensities reveals
      that the beta-sheet has a slight preferential alignment parallel to the direction
      of compression; i.e., deviation from uniaxial symmetry is observed. In addition,
      the sheet is found to lie flat on the aqueous surface, with (presumably) the
      polar side chains interacting with the aqueous subphase. Limitations and
      advantages of the theoretical approach are discussed.

PMID- 15875409
TI  - Self-doping effect in poly(o-methoxyaniline)/poly(3-thiopheneacetic acid) layer
      by-layer films.
AB  - Nanostructured films from two conducting polymers, poly(o-methoxyaniline) (POMA)
      and poly(3-thiopheneacetic acid) (PTAA), were fabricated with the layer-by-layer
      (LBL) technique. The electrochemical response of the LBL films differs from that
      of a POMA cast film, even in a potential range where PTAA is inactive. This is
      attributed to differences in the diffusion-controlled charge and mass transport,
      where distinct ionic species participate in the LBL films, as demonstrated by
      quartz crystal microbalance measurements. The results show that the transport
      properties of conducting polymers can be changed by alternation with layers of
      appropriate materials in LBL films.

PMID- 15875408
TI  - Liposome induced self-assembly of gold nanoparticles into hollow spheres.
AB  - Gold nanoparticles were prepared by the reduction of [(C7H15)4N]+ [AuCl4]- with
      3,4-ethylenedioxythiophene (EDOT) as reductant in toluene solution. The employed
      stabilizers include 3,3'-thiodipropionic acid (TDPA), 1-dodecanethiol (DDT), (+/
      )-10-camphorsulfonic acid (CSA), and 11-mercaptoundecanoic acid (MUA). The
      reaction processes were tracked by UV-vis and FT-IR spectroscopy, and the as
      prepared gold nanoparticles were characterized by scanning electron microscopy,
      transmission electron microscopy, energy-dispersive spectroscopy, and X-ray
      photoelectron spectroscopy measurements. When TDPA and MUA, which possess both -S
      and -COOH groups, were used as the stabilizer in the preparation, the as
      prepared nanoparticles could self-assemble into hollow spheres. While when DDT
      with a -SH group or CSA with a -SO3H group was used as the protecting agents,
      only discrete gold nanoparticles were observed. The results show that the groups
      of both -S- and -COOH in the stabilizer play an important role in forming the
      hollow nanospheres. It is proposed that the formation mechanism of the hollow
      spheres is a liposome that formed between -COO- and [(C7H15)4 N]+ could act as a
      template to induce the self-assembly of the gold nanoparticles into the hollow
      spheres.

PMID- 15875410
TI  - Thermally induced phase transitions and morphological changes in organoclays.
AB  - Thermal transitions and morphological changes in Cloisite organoclays were
      investigated by differential scanning calorimetry (DSC), thermogravimetric
      analysis (TGA), Fourier transform infrared (FTIR) spectroscopy, and in situ
      simultaneous small-angle X-ray scattering (SAXS) and wide-angle X-ray diffraction
      (WAXD) over the temperature range of 30-260 degrees C. On the basis of DSC and
      FTIR results, the surfactant component in organoclays was found to undergo a
      melting-like order-disorder transition between 35 and 50 degrees C. The
      transition temperatures of the DSC peaks (Ttr) in the organoclays varied slightly
      with the surfactant content; however, they were significantly lower than the
      melting temperature of the free surfactant (dimethyldihydrotallowammonium
      chloride; Tm = 70 degrees C). FTIR results indicated that within the vicinity of
      Ttr, the gauche content increased significantly in the conformation of surfactant
      molecules, while WAXD results did not show any change in three-dimensional
      ordering. Multiple scattering peaks were observed in SAXS profiles. In the SAXS
      data acquired below Ttr, the second scattering peak was found to occur at an
      angle lower than twice that of the first peak position (i.e., nonequidistant
      scattering maxima). In the data acquired above Ttr, the second peak was found to
      shift toward the equidistant position (the most drastic shift was seen in the
      system with the highest surfactant content). Using a novel SAXS modeling
      technique, we suggest that the appearance of nonequidistant SAXS maxima could
      result from a bimodal layer thickness distribution of the organic layers in
      organoclays. The occurrence of the equidistant scattering profile above Ttr could
      be explained by the conversion of the bimodal distribution to the unimodal
      distribution, indicating a redistribution of the surfactant that is nonbounded to
      the clay surface. At temperatures above 190 degrees C, the scattering maxima
      gradually broadened and became nonequidistant again but having the second peak
      shifted toward a scattering angle higher than twice the first peak position. The
      changes in SAXS patterns above 190 degrees C could be attributed to the collapse
      of organic layers due to desorption and/or degradation of surfactant component,
      which was supported by the TGA data.

PMID- 15875411
TI  - Self-diffusion of methane in single-walled carbon nanotubes at sub- and
      supercritical conditions.
AB  - The diffusivities of methane in single-walled carbon nanotubes (SWNTs) are
      investigated at various temperatures and pressures using classical molecular
      dynamics (MD) simulations complemented with grand canonical Monte Carlo (GCMC)
      simulations. The carbon atoms at the nanotubes are structured according to the
      (m, m) armchair arrangement and the interactions between each methane molecule
      and all atoms of the confining surface are explicitly considered. It is found
      that the parallel self-diffusion coefficient of methane in an infinitely long,
      defect-free SWNT decreases dramatically as the temperature falls, especially at
      subcritical temperatures and high loading of gas molecules when the adsorbed gas
      forms a solidlike structure. With the increase in pressure, the diffusion
      coefficient first declines rapidly and then exhibits a nonmonotonic behavior due
      to the layering transitions of the adsorbed gas molecules as seen in the
      equilibrium density profiles. At a subcritical temperature, the diffusion of
      methane in a fully loaded SWNT follows a solidlike behavior, and the value of the
      diffusion coefficient varies drastically with the nanotube diameter. At a
      supercritical temperature, however, the diffusion coefficient at high pressure
      reaches a plateau, with the limiting value essentially independent of the
      nanotube size. For SWNTs with the radius larger than approximately 2 nm,
      capillary condensation occurs when the temperature is sufficiently low, following
      the layer-by-layer adsorption of gas molecules on the nanotube surface. For SWNTs
      with a diameter less than about 2 nm, no condensation is observed because the
      system becomes essentially one-dimensional.

PMID- 15875412
TI  - Gold nanoparticle patterning of silicon wafers using chemical e-beam lithography.
AB  - This paper demonstrates a novel facile method for fabrication of patterned arrays
      of gold nanoparticles on Si/SiO2 by combining electron beam lithography and self
      assembly techniques. Our strategy is to use direct-write electron beam patterning
      to convert nitro functionality in self-assembled monolayers of 3-(4-nitrophenoxy)
      propyltrimethoxysilane to amino functionality, forming chemically well-defined
      surface architectures on the 100 nm scale. These nanopatterns are employed to
      guide the assembly of citrate-passivated gold nanoparticles according to their
      different affinities for amino and nitro groups. This kind of nanoparticle
      assembly offers an attractive new option for nanoparticle patterning a silicon
      surface, as relevant, for example, to biosensors, electronics, and optical
      devices.

PMID- 15875413
TI  - Fabrication of nanoparticulate porous LaOF films through film growth and thermal
      decomposition of ion-modified lanthanum diacetate hydroxide.
AB  - This paper first reports fabrication of macro/nanotextured rare-earth oxyfluoride
      films. Usage of ion-modified lanthanum diacetate hydroxide (LDAH) as self
      templates was successful in producing nanoparticulate lanthanum oxyfluoride
      (LaOF) films. LDAH template films were deposited on glass substrates through a
      chemical bath deposition in solutions composed of lanthanum acetate
      sesquihydrate, methanol, trifluoroacetic acid, and aqueous ammonia. The LDAH
      films had a unique, nestlike morphology owing to a two-dimensional hexagonal
      crystal growth. Modification of LDAH with trifluoroacetate ions led to formation
      of LaOF after pyrolyzing the template films at temperatures of 400-600 degrees C
      in air. The resultant LaOF films had a nanoparticulate porous microstructure,
      maintaining the morphology of the original LDAH template films. It was also
      successful to incorporate Eu3+ ions into LaOF through deposition of the LDAH film
      in a solution containing europium acetate tetrahydrate. The characteristic
      photoluminescence from Eu(3+) was observed with an ultraviolet-light excitation
      at 273 nm, indicating that Eu3+ was homogeneously distributed in LaOF host
      crystals. Thus the ion-modification of LDAH was also demonstrated to be a useful
      method for preparing nanostructured rare-earth oxyfluoride materials
      havingvarious cationic compositions.

PMID- 15875414
TI  - Noncovalent imprinting in the shell of core-shell nanoparticles.
AB  - Propranolol was imprinted using noncovalent interactions in the shell of core
      shell nanoparticles prepared by aqueous emulsion polymerization in the presence
      and absence of toluene. The imprinted particles were characterized, and their
      capacity to rebind propranolol from both organic and aqueous media was analyzed.
      Results showed that the amount of template incorporated into the polymer and the
      presence of toluene as a "porogenic" agent influenced the ability of the
      nanoparticles obtained to rebind propranolol. The presence of toluene during
      imprinting increased rebinding by about 2-fold in buffer and by 3-fold in
      toluene, compared with similar materials made in the absence of toluene during
      imprinting. It also influenced the final surface area of the particles. Binding
      site affinity, assessed by radioligand displacement, was measured as IC50 values
      of about 1-10 microM. This compares with about 3 microM for bulk polymer made
      with a similar composition. Finally, to demonstrate the advantages of structured
      particles for analytical applications a new property, fluorescence, was
      incorporated into the core of the particles without interfering with the
      imprinted shell and its ability to rebind propranolol.

PMID- 15875415
TI  - Incorporation of organic groups within the channel wall of spin-on mesostructured
      silica films by a vapor infiltration technique.
AB  - Organically functionalized mesoporous silica films have been prepared by a novel
      synthetic procedure that involves spin-coating of mesostructured silica films and
      a vapor infiltration (VI) technique, using organosiloxanes, before the removal of
      surfactant. The VI-treated mesostructured films were characterized using X-ray
      diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and a field
      emission scanning electron microscope (FE-SEM). Nitrogen adsorption/desorption
      measurements were performed using films attached with a silicon substrate. The
      XRD and FE-SEM measurements show that the mesochannel wall, densified and
      modified with organosilyl groups by the VI treatment, hardly contracts under
      calcination. FE-SEM observations for the films' cross section support the view
      that organosiloxane vapor is not deposited on the surface of the film. These
      results show that organosiloxane molecules penetrate the film and are selectively
      incorporated into the silica wall. Thus, hydrophobic mesoporous silica films can
      be synthesized without a reduction in pore size, a result that cannot be attained
      by conventional grafting and co-condensation methods. The excellent high porosity
      and hydrophobicity of the mesostructured composite films may be of advantage for
      next-generation low-k dielectric films.

PMID- 15875416
TI  - PH effects in the complex formation and blending of poly(acrylic acid) with
      poly(ethylene oxide).
AB  - The effect of pH on the complex formation between poly(acrylic acid) (PAA) and
      poly(ethylene oxide) (PEO) has been studied in aqueous solutions by turbidimetric
      and fluorescent methods. It was shown that the formation of insoluble
      interpolymer complexes is observed below a certain critical pH of complexation
      (pH(crit1)). The formation of hydrophilic interpolymer associates is possible
      above pH(crit1) and below a certain pH(crit2). The effects of polymer
      concentrations in solution and PEO molecular weight as well as inorganic salt
      addition on these critical pH values were studied. The polymeric films based on
      blends of PAA and PEO were prepared by casting from aqueous solutions with
      different pHs. These films were characterized by light transmittance measurements
      and differential scanning calorimetry. The existence of the pH value above which
      the polymers form an immiscible blend was demonstrated. The transitions between
      the interpolymer complex, miscible blend, and immiscible blend caused by pH
      changes are discussed. The recommendations for preparation of homogeneous
      miscible films based on compositions of poly(carboxylic acids) and various
      nonionic water-soluble polymers are presented.

PMID- 15875417
TI  - Application of density functional theory to analysis of energetic heterogeneity
      and pore size distribution of activated carbons.
AB  - A new approach based on the nonlocal density functional theory to determine pore
      size distribution (PSD) of activated carbons and energetic heterogeneity of the
      pore wall is proposed. The energetic heterogeneity is modeled with an energy
      distribution function (EDF), describing the distribution of solid-fluid potential
      well depth (this distribution is a Dirac delta function for an energetic
      homogeneous surface). The approach allows simultaneous determining of the PSD
      (assuming slit shape) and EDF from nitrogen or argon isotherms at their
      respective boiling points by using a set of local isotherms calculated for a
      range of pore widths and solid-fluid potential well depths. It is found that the
      structure of the pore wall surface significantly differs from that ofgraphitized
      carbon black. This could be attributed to defects in the crystalline structure of
      the surface, active oxide centers, finite size of the pore walls (in either wall
      thickness or pore length), and so forth. Those factors depend on the precursor
      and the process of carbonization and activation and hence provide a fingerprint
      for each adsorbent. The approach allows very accurate correlation of the
      experimental adsorption isotherm and leads to PSDs that are simpler and more
      realistic than those obtained with the original nonlocal density functional
      theory.

PMID- 15875418
TI  - Prewetting transitions for a model argon on solid carbon dioxide system.
AB  - Grand canonical transition matrix Monte Carlo simulations are used to investigate
      the phase behavior of the model argon on solid carbon dioxide system introduced
      by Ebner and Saam (Phys. Rev. Lett. 1977, 38, 1486). Our results indicate that
      the system exhibits first-order prewetting transitions at temperatures above a
      wetting temperature of Tw = 0.598(5) and below a critical prewetting temperature
      of Tpwc approximately 0.92. The wetting transition is identified by determining
      the temperature at which the difference between the bulk vapor-liquid and
      prewetting saturation chemical potentials goes to zero. Coexistence is directly
      located at a given temperature by obtaining a density probability distribution
      from simulation data and utilizing histogram reweighting to determine the
      conditions that satisfy phase coexistence. Structural properties of the adsorbed
      films are also examined.

PMID- 15875419
TI  - Lateral nanopatterns in thin diblock copolymer films induced by selective
      solvents.

PMID- 15875420
TI  - Ring-shaped morphology of "crew-cut" aggregates from ABA amphiphilic triblock
      copolymer in a dilute solution.

PMID- 15875421
TI  - Degassing and temperature effects on the formation of nanobubbles at the
      mica/water interface.

PMID- 15875422
TI  - Patterned TiO2/SnO2 bilayer type photocatalyst. 3. Preferential deposition of Pt
      particles on the SnO2 underlayer and its effect on photocatalytic activity.

PMID- 15875423
TI  - In search of financial viability: hospital-based v. freestanding home care.
AB  - In the continually changing and perpetually unpredictable nature of Medicare and
      Medicaid reimbursement, many hospitals and health care systems are rethinking
      their relationships with their affiliated home care and hospice programs. As the
      books of many of these programs show an increasing amount of red ink, many
      hospitals are spinning off their home care and hospice services into independent
      entities with their own individual operating structures. This article provides
      insight into one health care system's transitioning of its home care services
      into a freestanding entity.

PMID- 15875424
TI  - The lifespan merger sucess story: combining resources to offer better home health
      services.
AB  - In 1996, "Lifespan" was born when four home care agencies in Battle Creek,
      Michigan, merged to create a wholly owned subsidiary of the Battle Creek Health
      System (BCHS), a community health care delivery organization that provides acute
      care, long-term care, psychological services, outpatient care, home health care,
      and occupational and business services. By banding together to effect savings
      through joint contract purchasing and shared services, Lifespan and BCHS have
      formed a communal relationship that allows the two to offer a seamless continuum
      of care without establishing wholly discrete organizations. Lifespan has thus
      been free to independently make mutually beneficial partnerships with an
      information technology company to enhance patient care services to their clients.

PMID- 15875425
TI  - Banner home Care: a key element in the unparalleled success of Baner Health Care.

PMID- 15875426
TI  - Reinventing aging: baby boomers and civic engagement.
AB  - Approximately 77 million babies were born in the United States during the boom
      years of 1946-1964. In 2011, the eldest will turn 65, and, on average, can expect
      to live to age 83. Many will continue well into their 90s. These baby boomers
      will soon have the opportunity to redefine the meaning and purpose of their older
      years. As some of the demands of work and family that have commanded their
      attention in mid-life recede, boomers will have the potential to become a social
      resource of unprecedented proportions by actively participating in the life of
      their communities.

PMID- 15875427
TI  - Life with father: if I only knew then what I know now.
AB  - For eleven years I begged my obstinate elderly father to allow a caregiver to
      help him with my ailing mother, who needed full-time care after a massive heart
      attack. But he adamantly insisted on taking care of her himself. Every caregiver
      I hired lasted about three days and then I'd get the familiar call: "Jacqueline,
      I just can't work with your father. His temper is impossible to handle. He
      screams and yells and stands over me--and he won't let me do anything. I don't
      think you'll be able to get him to accept help until he's on his knees himself".

PMID- 15875428
TI  - Measuring quality of care nationwide.
AB  - This brief summarizes a study conducted by researchers at the RAND Corporation
      that measured the quality of health care for randomly selected adults from 12
      communities across the United States. Because the researchers used 439 quality
      indicators to evaluate health care performance in 30 clinical areas, including
      diabetes mellitus, hypertension, heart disease, and related preventive care, the
      size and comprehensiveness of this study is particularly noteworthy. The findings
      reveal comparable deficits in adherence to standard care processes by both
      inpatient and outpatient providers within the 12 chosen communities. Overall,
      study participants received only half of the care consistent with evidence-based
      knowledge. Thus, study results provide systematic evidence detailing the gaps
      between the science and the practice of health care delivery throughout the
      country.

PMID- 15875429
TI  - Reverse mortgages: a novel tool for financing long-term health care needs.
AB  - There is growing agreement among policymakers, health care professionals, and the
      aging industry in general that reverse mortgages can play an important role in
      financing our nation's long-term health care system, addressing many of our
      seniors' unmet needs.

PMID- 15875430
TI  - Consensus conference puts forth recommendations to improve end-of-life care.

PMID- 15875431
TI  - Time allocation planning: a day in the life of a home care salesperson.

PMID- 15875433
TI  - How high is your CQ?

PMID- 15875432
TI  - "Control the controllable".
AB  - At the beginning of each year we all make resolutions--both for ourselves and our
      businesses. We intend to implement these resolutions to make us better, smarter,
      thinner. Studies reveal again and again that by mid-February many of us have
      dropped our resolutions along the road through Everyday Life, as this first
      question highlights.

PMID- 15875434
TI  - Expression of Hsp72 in lymphocytes in patients with febrile convulsion.
AB  - The pathophysiology of febrile convulsion, the most common childhood neurologic
      disease, remains unclear. In this study, we investigated what role a heat shock
      protein plays in this disease. We enrolled eight boys and two girls with febrile
      convulsion and 10 age-matched healthy controls. We did a biosynthetic evaluation
      of both groups by separating lymphocytes and measuring the expression of heat
      shock protein 72 before and after heat shock treatment. Before the treatment,
      both groups were found to have small amounts of constitutive heat shock protein
      72. Afterwards, its expression increased in both groups, and no statistical
      difference was found between the increases in the two groups. In addition, there
      was no obvious difference in the susceptibility to produce heat shock proteins.
      However, the febrile convulsion group was found to have a significant decrease in
      phosphorylation of heat shock protein 72. These results suggest the possible
      involvement of post-translational modification of heat shock proteins, most
      likely phosphorylation, in the pathogenesis of febrile convulsion.

PMID- 15875435
TI  - Treatment of macular holes with indocyanine green-assisted retinal internal
      limiting membrane peeling.
AB  - Removal of the internal limiting membrane (ILM) has been proposed as a useful
      surgical approach to enhance the closure of macular holes and the adjuvant
      indocyanine green (ICG) staining has been reported to facilitate ILM peeling.
      This study attempts to determine the efficacy and safety of ICG-assisted retinal
      ILM peeling in macular hole surgery. Seventeen eyes of 16 patients with stage 3
      or 4 macular holes were included. All eyes underwent a pars plana vitrectomy,
      including the peeling of the posterior cortical hyaloid when necessary. ICG dye
      (0.5%) was instilled into the posterior vitreous cavity and left in place for 30
      seconds. The retinal ILM was peeled after ICG removal. The procedure was
      completed with an intraocular tamponade (16% perfluoropropane), after which the
      patient remained in a face-down position for 1-2 weeks. ICG staining greatly
      facilitated the surgeon's ability to visualize and peel the ILM during surgery.
      Anatomic closure of the macular hole was achieved in 15 eyes (88.2%). However,
      the postoperative best-corrected visual acuity improved by two or more Snellen
      lines in only three eyes, remained the same in 13 eyes, and deteriorated in one
      eye. There was no statistically significant improvement in postoperative visual
      acuity. In conclusion, while ICG facilitates ILM peeling by providing a stark
      contrast between the stained ILM and the unstained retina, our results revealed
      that ICG might cause retinal damage and hinder visual acuity improvement.

PMID- 15875436
TI  - A prelimary study of a health-promoting lifestyle among South Asian women in
      Taiwan.
AB  - The purpose of this study was to determine and understand the predicting factors
      of a health-promoting lifestyle (HPL) in Southeast Asian women in Taiwan. One
      hundred and five Southeast Asian women in Tainan were recruited. Face-to-face
      interviews with structured questionnaires were used for data collection. The
      findings showed that, among the six dimensions of HPL, subjects scored highest in
      self-actualization and lowest in health responsibility. Subjects who could read
      and write Chinese had a more positive HPL; stepwise regression analysis revealed
      that the ability to read Chinese could explain 26.2% of the total variance of HPL
      in Southeast Asian women. The results of this study can help health care
      professionals understand the HPL and to design appropriate health-promoting
      educational programs to improve the well-being and overall quality of life of
      Southeast Asian women in Taiwan.

PMID- 15875437
TI  - Related factors and consequences of menstrual distress in adolescent girls with
      dysmenorrhea.
AB  - This study investigated symptoms, related factors, and consequences of menstrual
      distress in adolescent girls with dysmenorrhea. A total of 198 participants were
      recruited by convenience sampling from a technical college in Tainan County,
      Taiwan. Four instruments were used to collect data: a Demographic Data
      Questionnaire, a Menstrual Distress Questionnaire, the Short Form McGill Pain
      Questionnaire, and an Adolescent Menstrual Attitude Questionnaire. The top five
      symptoms of menstrual distress were cramps, fatigue, backache, swollen abdomen,
      and tender breasts. Results of stepwise multiple regression indicated that the
      best subsets for predicting adolescent menstrual distress, including age,
      mother's occupation, menstrual pain, and menstrual attitude, accounted for 59% of
      total variance. From the correlation analysis, the more severe the menstrual
      distress, the higher the impact on daily activities as well as the more frequent
      the absence from class and analgesic usage. The results of this study may provide
      a useful reference for school nurses designing menstrual health programs for
      adolescents.

PMID- 15875438
TI  - Heparin-induced cardiac tamponade and life-threatening hyperkalema in a patient
      with chronic hemodialysis.
AB  - Heparin, a commonly used anticoagulant agent, is frequently used in patients
      undergoing hemodialysis. As with most medications, heparin has a significant side
      effect profile. Two of its most important side effects, major bleeding and
      hyperkalemia, may be devastating without immediate diagnosis and treatment. Major
      bleeding such as gastrointestinal, genitourinary or intracranial bleeding is
      occasionally encountered and rarely neglected. However, heparin-induced cardiac
      tamponade is rarely encountered and may be easily overlooked. Another side
      effect, heparin-induced hyperkalemia, an unusual but well-described side effect,
      is frequently forgotten until life-threatening arrhythmia has occurred. We report
      a case involving a 40-year-old male patient with uremia, who had received heparin
      for 10 days for deep vein thrombosis in the left lower extremity. Hemopericardium
      with cardiac tamponade and life-threatening hyperkalemia were both noted in this
      patient.

PMID- 15875439
TI  - Hypophosphatasia in Taiwan: report of two cases.
AB  - Hypophosphatasia is a rare inherited metabolic disease characterized by rickets
      with reduced plasma and tissue alkaline phosphatase activity. It may be present
      in infancy, childhood, or adulthood. Various clinical manifestations reflect
      different forms of alkaline phosphatase gene expression. In this report, we
      present two cases of hypophosphatasia, one of the infantile and the other of the
      adult form. The infantile case presented with failure to thrive, hypotonia, and
      radiologic rickets at 4 months old. The adult case had repeated fractures and
      marked loss of bone density demonstrated by radiographs. Both cases showed
      extremely low levels of alkaline phosphatase. To the best of our knowledge, they
      are the first reported patients with hypophosphatasia from the Taiwanese
      population.

PMID- 15875440
TI  - Nasal septum chondroma: a case report.
AB  - Chondromas of the nasal septum are rare. Since its first literary description in
      1842, only about 140 cases have been reported. We present the case of a 38-year
      old female who reported intermittent nasal bleeding and nasal obstruction for 3
      months. A reddish mass arising from the nasal septum was found by endoscope. The
      tumor was removed under endoscopic guidance and histopathologic examination
      revealed chondroma composed of well-differentiated chondrocytes. No recurrence
      was noticed after 6 months of follow-up. Despite their rarity, chondromas should
      be taken into consideration in the differential diagnosis of nasal tumors,
      especially those arising from the nasal septum.

PMID- 15875441
TI  - Understanding and managing coma stimulation: are we doing everything we can?
AB  - The incidence of people surviving with traumatic brain injury is rising at a
      remarkable pace. Unfortunately, patients also experience some form of coma and
      significant deficits (ie, cognitive, functional, etc). The focus is shifting from
      saving these patients to trying to figure out what else can be done for them? In
      the past, patients were medically maintained, stabilized, and then sent to
      rehabilitation centers for coma stimulation, in the hope of waking up their
      reticular activating system. Today, healthcare professionals are being encouraged
      to research and explore the possibility of implementing structured coma
      stimulation programs as early as 72 hours postinjury in the intensive care unit.
      Starting early is of paramount importance to a patient's survival, quality of
      life, and overall long-term prognosis. The goal of this article is to educate
      healthcare professionals (in the hospital setting) about managing and
      implementing structured sensory stimulation sessions.

PMID- 15875442
TI  - Meningococcal meningitis in critical care: an overview, new
      treatments/preventions, and a case study.
AB  - Meningococcal meningitis (MM) is a disease process that can become insidious and
      deadly in a short amount of time if not properly diagnosed. New and effectively
      known treatments and preventions are the key to improve recovery. The Neisseria
      meningitidis (NM) bacteria is the culprit in the MM discussed in this article.
      The pathophysiology, symptoms, and assessment are important to review, as well as
      typical antibiotic therapy and other treatments. Morbidity and mortality is
      affected by the improvement of these therapies. Critical care nurses must
      correctly and prudently assess their patients quickly for rapid response to
      treatment. The vaccine for the NM bacteria associated with the serotype B is not
      available at this time. College freshmen are the most vulnerable population in
      contracting the disease because of small living spaces and lifestyle habits that
      increase their association with the disease. The issue of prophylactically giving
      the vaccine is controversial but may become necessary because of the increase in
      incidence in the last 5 years on college campuses. Chemoprophylaxis efficacy may
      also be of help to those healthcare workers exposed as well as to those
      individuals at high risk for contracting the disease after an exposure. Public
      health concerns with community and college campus participation and education can
      be key to a sense of well-being among those possible individuals who may be
      exposed. Steroid, coagulapathy, and immunotherapy, as well as other new
      treatments, are worth investigating and pursuing in these times of increased risk
      to certain vulnerable populations of people.

PMID- 15875443
TI  - Cerebral vasospasm after subarachnoid hemorrhage: an update.
AB  - Cerebral vasospasm is a significant problem after subarachnoid hemorrhage, with
      often devastating consequences. Its pathogenesis remains poorly understood
      despite extensive research. Owing to the lack of a clear etiology, medical
      treatment is still largely limited to triple-H therapy and calcium channel
      blockers, although newer treatments such as percutaneous transluminal angioplasty
      and papaverine infusion are becoming more common. Clinical symptoms are often
      first noted by the registered nurse, who must then alert the physician to the
      need for diagnostic workup and therapy. Caring for patients after subarachnoid
      hemorrhage requires awareness of the potential for the development of vasospasm,
      and knowledge of the steps necessary to ensure its timely diagnosis and
      treatment. This article will review the current body of knowledge as it pertains
      to vasospasm and outline the direction of ongoing research.

PMID- 15875444
TI  - Innovations in the management of cerebral injury.
AB  - During the past decade, brain tissue oxygen monitoring has been studied
      predominantly in Europe. Cerebral oxygenation monitoring was implemented in many
      intensive care units and correlations of intracranial pressure, cerebral
      perfusion pressure, end-tidal carbon dioxide monitoring, fever and partial
      pressure of brain tissue oxygenation (Pbto2) have been described (Crit Care
      Nurse. 2003;23[4, pt 1]:17-27). The monitoring of brain tissue oxygen is now
      being done and researched in the United States. This article will discuss the
      history of treatment of traumatic brain injury and how treatment interventions
      are changing with the latest technological advances in monitoring of cerebral
      oxygen levels and suggested interventions and factors that affect brain tissue
      oxygenation. It is clear that by understanding the causes of hypoxia and ischemia
      -along with the interventions to treat them--the critical care team will be
      better able to prevent low oxygen states in the brain and optimize treatment,
      thus improving patient outcome.

PMID- 15875445
TI  - Therapeutic hypothermia in traumatic brain injury.
AB  - Traumatic brain injury is a leading cause of death by trauma in adults in the
      United States and a major contributor to permanent physical, emotional, and
      psychological disabilities. Therapeutic hypothermia, defined as cooling of the
      body to less than 36 degrees C, has been shown to decrease mortality and
      morbidity and improve long-term outcomes by protecting the brain from secondary
      brain injury. The most commonly seen benefits of hypothermic temperatures of 32
      degrees C to 33 degrees C are a significant reduction in intracranial
      hypertension and improved cerebral perfusion and oxygenation. Although evidence
      to date is insufficient to recommend the routine use of therapeutic hypothermia
      outside of the research setting, therapeutic hypothermia is used in multiple
      healthcare facilities in the world. The following article will define hypothermia
      and provide critical information necessary to provide care for the critically ill
      patient under therapeutic hypothermia. It will define the processes of brain
      injury and how hypothermia is thought to counteract those to protect the brain.
      Also included is a review of 2 major randomized, controlled trials of hypothermia
      for traumatic brain injury that have been instrumental in establishing guidelines
      and directing further research.

PMID- 15875446
TI  - Case management "within the walls": a glimpse into the future.
AB  - Case management integrates patient and provider satisfaction, takes into
      consideration cost factors, and provides a means of managing the individual's
      health concerns. It offers nurses an opportunity to demonstrate their roles in
      multidisciplinary healthcare teams. Using the case management approach, nurse
      case managers can optimize client self-care, decrease fragmentation of care,
      provide quality care across a continuum, enhance patients' quality of life,
      decrease length of hospitalization, increase patient and staff satisfaction, and
      promote the cost-effective use of scarce resources. This article will review case
      management, acute care case management, the essential characteristics and job
      responsibilities of the nurse case manager, and the stages of nursing case
      management. This article presents the nurse case manager's involvement with a
      patient in the critical care unit who sustained an aneurysmal subarachnoid
      hemorrhage. A glimpse into the future will be viewed.

PMID- 15875447
TI  - Critical rehabilitation of the patient with spinal cord injury.
AB  - Most healthcare practitioners have worked with patients with spinal cord injury
      at some point in their career, for some it is a specialty. The critical care area
      usually only has patient with spinal cord injury for a brief time before they are
      transferred. More recently, there are longer intensive care unit stays due to
      multiple trauma and lack of insurance. Nurses must be cognizant of indications,
      contraindications, and best practice interventions to contribute positively to
      patient's long-term outcomes. As part of the multispecialty team, nurses can be
      pivotal in preventing secondary complications, especially pressure ulcers.
      Rehabilitation team members can be consulted early to provide expertise in
      managing this complex diagnostic group.

PMID- 15875448
TI  - Traumatic brain injury: a review.
AB  - Traumatic brain injury (TBI) is defined as "a blow or jolt to the head ...which
      can disrupt the function of the brain" (CDC. Traumatic brain injury [TBI]: Topic
      Home. 2004 [http://www.cdc.gov]). TBI changes the lives of approximately 2
      million persons each year in the United States. Rapid diagnosis and treatment are
      imperative to promote optimum outcomes. The critical care clinician who is able
      to identify and treat appropriately utilizing best practice guidelines may
      significantly reduce the morbidity and mortality of TBI. This article describes
      the classification, mechanism of injury, pathophysiology, and clinical
      therapeutic management strategies identified as best practice for TBI.

PMID- 15875449
TI  - The importance of maintaining spinal precautions.
AB  - Spinal injuries are devastating, often leaving the patient paralyzed or with a
      permanent deficit. Aspiring athletes may not be able to persue their dreams
      secondary to a spinal injury; families are often left without a major wage earner
      to support them; and individuals are dependent upon others for the fulfillment of
      their basic needs. Education is essential for the prevention of primary and
      secondary spinal injuries; nurses play a key role in both these areas.

PMID- 15875450
TI  - Acute pain and the critically ill trauma patient.
AB  - Pain is a frequent experience throughout our lifetime, and each person responds
      in a different manner to every pain experience. Critically ill trauma patients
      are obviously more likely to experience pain due to their injuries or iatrogenic
      causes. To optimize pain management for trauma patients, critical care nurses
      must continually be aware of the potential for pain. However, pain assessment for
      critically ill patients is usually complicated by their inability to express the
      subjective component of their pain experience. Understanding the pathophysiology
      of pain facilitates the assessment of the objective components of pain. It is
      imperative for the critical care nurse to function as the patient advocate
      especially regarding pain management issues.

PMID- 15875451
TI  - Inflammatory bowel disease and endothelin-1: a review.
AB  - Inflammatory bowel disease (IBD) appears to be an inappropriate response to an
      antigen that leads to chronic inflammation rather than repair. This review looks
      at the role of endothelin-1 (ET-1) as a proinflammatory agent in IBD. ET-1
      antagonists in animal models reduce the incidence and severity of IBD. These
      antagonists may be useful for treatment of IBD in humans.

PMID- 15875452
TI  - Processing of threat-related information outside the focus of visual attention.
AB  - This study investigates whether threat-related words are especially likely to be
      perceived in unattended locations of the visual field. Threat-related, positive,
      and neutral words were presented at fixation as probes in a lexical decision
      task. The probe word was preceded by 2 simultaneous prime words (1 foveal, i.e.,
      at fixation; 1 parafoveal, i.e., 2.2 deg. of visual angle from fixation), which
      were presented for 150 ms, one of which was either identical or unrelated to the
      probe. Results showed significant facilitation in lexical response times only for
      the probe threat words when primed parafoveally by an identical word presented in
      the right visual field. We conclude that threat-related words have privileged
      access to processing outside the focus of attention. This reveals a cognitive
      bias in the preferential, parallel processing of information that is important
      for adaptation.

PMID- 15875453
TI  - Estimating one's own and one's relatives' multiple intelligence: a study from
      Argentina.
AB  - Participants from Argentina (N = 217) estimated their own, their partner's, their
      parents' and their grandparents' overall and multiple intelligences. The
      Argentinean data showed that men gave higher overall estimates than women (M =
      110.4 vs. 105.1) as well as higher estimates on mathematical and spatial
      intelligence. Participants thought themselves slightly less bright than their
      fathers (2 IQ points) but brighter than their mothers (6 points), their
      grandfathers (8 points), but especially their grandmothers (11 points).
      Regressions showed that participants thought verbal and mathematical IQ to be the
      best predictors of overall IQ. Results were broadly in agreement with other
      studies in the area. A comparison was also made with British data using the same
      questionnaire. British participants tended to give significantly higher self
      estimates than for relatives, though the pattern was generally similar. Results
      are discussed in terms of the studies in the field.

PMID- 15875454
TI  - A pragmatic guideline for evaluation of social intervention.
AB  - Considering the many theoretical and methodological viewpoints in the field of
      evaluation, a guideline was established to facilitate the evaluation of social
      intervention programs. For this purpose, the goals of the evaluation were taken
      into account: (a) planning interventions, (b) learning and continuous improvement
      of interventions, (c) programming policies, and (d) transformation of society.
      These goals will determine the perspective of the analysis selected (focusing on
      the evaluand or the context) and the strategies for change employed (focusing on
      processes or results). The elements that, according to Shadish, Cook, and
      Levinton (1991), constitute the theory of evaluation (evaluand, value, building
      of knowledge, and uses) have also been considered. The analysis of all these
      components led to the elaboration of a guideline to orient the practice of
      evaluation from a pragmatic perspective, in accordance with the demands and needs
      of a certain social context.

PMID- 15875455
TI  - Positive emotions in volunteerism.
AB  - Volunteerism is a well consolidated social phenomenon in our society. However,
      its rapid growth in the last few years has complicated the integration of
      theoretical knowledge and its application in organizational settings. Taking into
      account that nowadays, one of the chief problems of volunteer organizations is
      sustained volunteer service, the object of this work is to verify, within the
      context of the psychosocial model of sustained volunteerism (Vecina, 2001), the
      type of relation between the experience of positive emotions in volunteers and
      their intention of remaining in the organization. This work was carried out on a
      sample of volunteers who had been in service for less than one year prior to this
      study.

PMID- 15875456
TI  - Psychosocial adaptation in relatives of critically injured patients admitted to
      an intensive care unit.
AB  - The aim of this study is to analyze how the length of time a patient spends in an
      Intensive Care Unit (ICU) affects close relatives, with regard to specific
      clinical variables of personality, family relationships and fear of death. The
      study group consisted of 57 relatives of seriously ill patients admitted to the
      ICU of "Virgen del Rocio" Rehabilitation and Trauma Hospital (Seville, Spain).
      The instruments applied were: a psychosocial questionnaire, clinical analysis
      questionnaire, family environment scale and fear of death scale. The relatives of
      patients admitted to ICU obtained higher scores in hypochondria, suicidal
      depression, agitation, anxious depression, guilt-resentment, paranoia,
      psychasthenia, psychological maladjustment and self-expression, and less in fear
      of their own death, as when compared to interviews with the same relatives 4
      years later. The length of time a patient spent in the ICU influenced relatives
      in some clinical variables of personality, family relationships and fear of death

PMID- 15875457
TI  - AIDS and social exclusion: personality features or adaptive behaviors?
AB  - The purpose of this survey is to detect common personality features in people
      infected with AIDS who have a case history of drug addiction and who live in a
      situation of social exclusion. The sample comprised 105 male participants from
      the Autonomous Community of Andalusia, divided into 4 groups: (a) 30 men with
      AIDS, having an intravenous drug addiction case history and who live in a
      condition of social exclusion; (b) 30 men with IVDA case history, also living in
      a situation of social exclusion; (c) 15 men in a social exclusion condition; and
      (d) 30 men in a condition of social adaptation. The evaluation instruments were
      an author-designed semi-structured interview and the Multiaxial Clinical
      Inventory (MCMI-II; Millon, 1987). Although some differences were found, the
      results indicate that there is no specific personality profile in the "social
      exclusion" population. People in a condition of social exclusion (AIDS, drug
      addicts, and poor people) may obtain similar scores in the variables studied, but
      there is no clear specific personality profile in the excluded population,
      although there may be certain situations in which the segregated groups present
      similar behaviors. Furthermore, these behaviors do not always correspond to
      personality features but are adaptive responses to a harsh and complex reality.

PMID- 15875458
TI  - Self-talk and affective problems in college students: valence of thinking and
      cognitive content specificity.
AB  - The aim of this study was to develop a Self-Talk Inventory for young adults. This
      inventory consisted of two scales. The Negative Self-Talk Scale included three
      categories of self-talk (depressive, anxious, and angry thoughts) and the
      Positive Self-Talk Scale, three categories (minimization, positive orientation,
      and coping self-instructions). Participants were 982 undergraduate students (Mean
      age = 20.35 years, SD = 2.16). They completed the self-talk scales together with
      the following scales to measure symptoms of affective disorders: the Center for
      Epidemiological Studies Depression Scale (CES-D), the State-Trait Anxiety
      Inventory (STAI), and the State-Trait Anger Expression Inventory (STAXI-T).
      Factor analyses confirmed the hypothesized structure for the Self-Talk Inventory.
      The relations between self-talk and symptoms of affective disorders (depression,
      anxiety, and anger) were also evaluated. In general, states-of-mind -SOM- ratios
      and negative cognitions showed a greater association with psychological symptoms
      than did positive cognitions. Results concerning the cognitive characteristics of
      depression, anxiety, and anger were mixed and partially supported the cognitive
      content specificity theory.

PMID- 15875459
TI  - Modification of coronary-prone behaviors in coronary patients of low socio
      economic status.
AB  - The purpose of this study is to determine the effectiveness of a group cognitive
      behavioral treatment to modify coronary-prone behaviors in patients from a fairly
      low social and educational level. Participants were 98 male coronary patients
      randomly allocated to one experimental and two control groups. All groups
      received standard medical treatment. The experimental group received an
      additional psychological treatment and one of the two control groups received a
      health education treatment. Results showed that only the psychological treatment
      group significantly reduced Pressured Drive and Speed-Impatience after treatment,
      and at 1- and 2-year follow-ups. Depression was also significantly reduced only
      in this group at 2-year follow-up. The results are considered a reliable first
      step in the process of validating this program designed to improve coronary heart
      disease patients' quality of life.

PMID- 15875460
TI  - See red? Turn pale? Unveiling emotions through cardiovascular and hemodynamic
      changes.
AB  - Cardiodynamic and hemodynamic reactions to emotion-eliciting film sequences were
      investigated. Thirty-two healthy subjects (12 women, 20 men) were randomly
      assigned to one of two groups. In the first group, anger was induced using
      selected scenes of the film "Ragtime." In the second group, scenes of the film
      "The Shining" were chosen to elicit fear. A documentary film was used as a
      baseline stimulus in both groups. EKG, impedance cardiography, and blood pressure
      were continuously monitored. The two emotional conditions elicited significant
      differential changes in subjective ratings and cardiovascular indices. Fear was
      associated with decreased cardiac output, increased total peripheral resistance,
      and a reduction in stroke volume and myocardial contractility. Anger was
      associated with an increase of cardiac output and small changes in total
      peripheral resistance. These results support the hypothesis that discrete
      emotions such as fear and anger elicit differential patterns of physiological
      responses.

PMID- 15875461
TI  - The neurophysiological validation of the hyperpolarization theory of internal
      inhibition.
AB  - The experiments in conscious non-immobilized rabbits showed that cessation of the
      reactions without reinforcement (elaboration of the internal inhibition) is
      accompanied by an enhanced phasic state, by alternation of activation and
      inhibition of neuron firing, and by the corresponding slow potential oscillation
      (SPO). These changes can be either localized, predominantly in the structures of
      conditioned stimulus, or, under enhancement of the inhibitory state, generalized
      in the brain structures. On the basis of our experience and published data, it is
      concluded that the above event results from relative enhancement of the
      inhibitory hyperpolarizing processes due to increase in reactivity of the
      inhibitory systems to stimulus, which acquires inhibitory properties during
      learning. Changes in the excitability and reactivity of neuron populations
      appearing during enhancement of the hyperpolarizing inhibition, and differing in
      the various brain structures, play an active role in the execution of the main
      function of the internal inhibition: limitation of excitation transmission to the
      effectors. An inhibitory mediator gamma aminobutyric acid (GABA) is of great
      importance in inhibiting the excitation in response to the stimulus which lost
      its biological significance. These experimental data and their interpretation in
      the light of published data give the basis for the development of the
      hyperpolarization theory of internal inhibition.

PMID- 15875462
TI  - Fitting Rasch model using appropriateness measure statistics.
AB  - In this paper, the distributional properties and power rates of the Lz, Eci2z,
      and Eci4z statistics when they are used as item fit statistics were explored. The
      results were compared to t-transformation of Outfit and Infit mean square. Four
      sample sizes were selected: 100, 250, 500, and 1000 examinees. The abilities were
      uniform and normal with mean 0 and standard deviation 1, and uniform and normal
      with mean -1 and standard deviation 1. The pseudo-guessing parameter was fixed at
      .25. Two ranges of difficulty parameters were selected: +/- 1 logits and +/- 2
      logits. Two test lengths were selected: 15 and 30 items. The results showed
      important differences between the T-infit, T-outfit, Lz, Eci2z, and Eci4z
      statistics. The T-oufit, T-infit, and Lz statistics showed poor standardization
      with estimated parameters because their distributional properties were not close
      to the expected values. However, the Eci2z and Eci4z statistics showed
      satisfactory standardization on all conditions. Further, the power rates of Eci2z
      and Eci4z were 5% to 10% higher than the power rates of Lz, T-outfit, and T-infit
      to detect items that do not fit Rasch model.

PMID- 15875463
TI  - [Ultrastructural analysis of the female breast alveolar ductulus cells in pre-
      and postmenopause].
AB  - Ultrastructural characteristics of ductular parenchyma epithelial and
      myoepithelial cells were analysed in 18 cases of normal female breast tissue.
      Different physiological states have been compared and that pre- and
      postmenopausal. Nuclei and cytoplasm of epithelial and myoepithelial cells have
      been examined and compared. There were obvious signs of secretion and that apical
      protein granules, "dense-core" granules and light vesicles and lipid vacuoles and
      glycogen granules were accumulated in the deeper parts of premenopausal breast
      epithelial cells cytoplasm. Morphologic equivalents of secretion and accumulated
      glycogen were presented in the postmenopausal breast epithelial cells.
      Ultrastructural morphologic characteristics of postmenopausal myoepithelial cells
      were not different from those in premenopausal breasts.

PMID- 15875464
TI  - [Biological activities of bone morphological protein in bone regeneration].
AB  - Bone matrix contents various development factors which control structuring and
      absorption and those factors play important role in bone and cartilage
      development. Bone morphological proteins are members of TGF-beta super family and
      their activity is certain becoming from the bone. This activity leads to the
      serial development processes which include chemo taxis, proliferation and
      differentiation which results in trans resistant formation of cartilage as well
      as production of life cells of a bone tissue. Biological activities of re
      combinative human bone morphogenetic protein 7 (rhBMP-7). induction bone
      formation of non critical size mandible defect of New Zealand rabbits were
      researched in the study. Markers of osteoblastic differential in the study
      included ALP specific activity. Histological analysis performed 7, 14, 30, 60
      postoperative days, C-T analysis with determination Bone Mineral Density value of
      new structured tissue within the defect was done 30 days. Results indicate that
      ectopic bone formation has been inducted with rhBMP-7 and histological analysis
      shown mature bone with collagen and ostheociti 60th day. Early 7 day granulocyte
      tissue with angiogenesis was detected, and after 30 days ostheoblastsis shown
      with a lot of vascular and mezenhimal tissue. Ostheogenetic processes were
      characteristic for typical inter membraneous ossification without cartilage
      tissue. ALP activity was significantly increased 21 days. C-T and Bone Mineral
      Density value shown density of new structured tissue determinate as bone (413
      mg/cm3 and 519 mg/cm3). Studies showed that concentration of 100 mg rhBMP-7 in
      collagen as career had strong ostheo inductive capacity. Conditions which module
      BMP depend ostheo induction should be considered in the future. Information could
      lead to improvements of rhBMP as substitution for bone graft in clinical
      practice.

PMID- 15875465
TI  - [BMI of the children attending elementary schools in Tuzla Canton].
AB  - BMI is frequently used in different studies as indicator of nutritional status.
      When BMI exceeds the limit values then it represents the risk factor leading to
      different diseases; therefore it is important to calculate BMI for young persons.
      In cases when BMI differs from the recommended value it is necessary to apply
      different measures in order to prevent diseases. The aim of this paper was to
      assess the present status and on the basis of the result obtained to assess the
      need for eventual preventive activities leading to healthy life stytes. This
      study was performed on a sample of 1544 school boys and girls aged eight, ten and
      fourteen attending first, third and seventh class of elementary school. The study
      covered four municipalities of Tuzla Canton: Tuzla, Lukavac, Gradanica and
      Kladanj, and both urban and rural areas. We used the method of anthropometric
      measurement (IBP International Biological Program) of body mass and body height,
      followed by calculation of BMI and statistical evaluation. This study found that
      the average BMI of girls and boys is increasinglongitudinally with the age, with
      significant change between 10 years and 14 years, without significant gen der
      difference. Boys aged eight have BMI 15.76, len years 16.52 and are similar to
      the BMI of girls aged eight 15.44 and ten years 16.59. Fourteen-year-old girls
      have BMI which is 19.54, higher than the BMI of boys at the same age which is
      18.75. Having in mind the range of BMI percentile values for normal nutritional
      status (from 5 to 85) the values for eight years old boys ranged from 14.1 to
      19.4, for ten-year-old boys from 13.4 to 19.2, and for fourteen-year-old boys
      from 13.6 to 19.5. The values for girls showed the following results; for eight
      year-old girls the value ranged from 13.9 to 20.6; for ten-year-old girls t'rom
      13.5 to 20.5 and fourteen-year-old girls from 13.7 to 19.6. In the sample there
      was 6.6% underweight children, and 15.2% overweight children, but the portion of
      overweight individuals is bigger in the sample of fourteen-year-old children.
      This fact leads to the need for permanent education of the overall population,
      focusing on children and youth and healthy life styles highlighting correction of
      diet.

PMID- 15875466
TI  - [Ischemic stroke as reaction to an acute stressful event].
AB  - The period following ischemic stroke can be considered as a reaction to a
      stressful event. Changes in cortisol secretion are one of the indicators of
      stress reaction. The aim of the study was to determine morning serum levels of
      cortisol in stroke patients within 48 hours and 15 days of ischemic stroke onset.
      Study group included 40 patients, 20 of them were females, mean age 65.3 +/- 10.3
      years. The patients did not receive any corticosteroid agents or spironolactone,
      and did not suffer from Cushing's or Addison's syndrome. Ischemic stroke was
      verified by computed tomography of the brain. The fluorometric method with DELFIA
      Cortisol immunoassay was used to determine morning serum cortisol levels.
      Reference values of the measured hormone were 201-681 nmol/l. The mean level of
      serum cortisol within 48 hours of stroke was 560.9 +/- 318.9 nmol/l, and on day
      15 it was 426.2 +/- 159.3 nmol/l, i.e. significantly lower (p < 0.02). On the
      first measurement, the level of serum cortisol was elevated in 32%, and on the
      second measurement in only 7.5% patients, which was also significantly lower (p <
      0.001). It was concluded that the stress reaction in ischemic stroke patients was
      more pronounced within the first 48 hours of stroke onset. Judging from the
      morning cortisol levels, the reaction to stress was considerably less pronounced
      15 days after stroke onset.

PMID- 15875467
TI  - [Perception of their social environment and their future in institutionalized
      school-age children].
AB  - Family home and institutions for children without parental care represent the
      rearing-environments where, from the early years, whole human development goes
      on. It's known today that despite the recognized importance of inborn traits, the
      influence of child-rearing environments dominates current models of development.
      The aim of the study was to investigate the satisfaction with the rearing
      environment of school-aged institutionalized children, their dominating feeling
      and if institutionalization affects life optimism for now and for the future. The
      study was conducted in two institutions in Bosnia and Herzegovina who share the
      same care model imitating the traditional Bosnian families where the older
      children care for the younger siblings. We took as a sample 30 institutionalized
      children aged 8-12, and for the control group 60 children matched by age and sex.
      Parents, children and teachers who gave their informed consent answered the
      questionnaires. It was confirmed that children without parental care are
      vulnerable group and in a great risk who need urgent help of professional
      multidisciplinary team of their close and broad environment. Lack of social
      support cause the withdrawing and suffering and can lead soon or later to
      problematic behaviour.

PMID- 15875468
TI  - [Some of middle age smokers' attitudes against smoking].
AB  - Smoking is pandemic spread in all parts of the population. Particularly, this is
      an autodestructive blind impulse or the vice. THE FORMULATION OF THE PROBLEM:
      This rough of smoking today incites an important interest, same with nonsmokers
      as with smokers, so the understanding of the harmfulness of smoking to their
      health in the population of the middle-age smokers has been the cause for this
      investigation. The aim of the investigation was to show the attitude of smokers
      toward smoking in a prospective study. The selection was performed according to
      the settled rules, as well as inquiry of 280 examinees, workers of Furniture
      Factory "Krivaja-Zavidovici". The examination group formed 140 smokers and the
      control group 140 nonsmokers, of the same age 35-45 years, and both gender.
      Received results were prepared statistically and the differences between groups
      were certified with chi2 test and t-test to the level of tasked signification ? =
      0.05. RESULTS: Relativly high percentage of smoker examinees (84.28%) confessed
      to consider smoking to be harmful to their health; still, they continue to smoke.
      DISCUSSION: The establishing of these precise indexes, which show the attitude of
      smoker-examinees toward smoking enables developing of strategic, along with
      simultaneous forecaster estimation of succesful prevention, in the sense of the
      conduction of this program about quitting smoking. CONCLUSIONS: Among workes of
      Furniture Factory "Krivaja-Zavidovici" high percentage of smoker examinees
      (84.28%) confessed to consider the smoking harmful to their health. Smoker
      examinees in more than 50% cases would like quitting to smoke.

PMID- 15875469
TI  - [Persistence of IgM anti-HAV in prolonged form of HAV-infection].
AB  - Persistence of IGM anti-HAV antibody in sera of patients with acute HAV-infection
      can be followed up to 55 weeks. Available literature does not provide significant
      information on persistence of IgM anti-HAV antibody in prolonged form of disease.
      In multi-centric prospective study of the HAV infection prolonged form we have
      examined persistence of IgM anti-HAV in 30 patients with acute form of disease
      and 60 patients with prolonged form of disease. The aim of work was to examine
      length of IgM anti-HAV persistence in sera of patients with prolonged form of
      disease in relation to sex, length of persistence of sera aminotranspherasis
      activities and circulating immune complexes and length of secretion of Ag-HAV in
      stool. MATERIAL AND METHODS: IgM anti-HAV, IgG anti-HAV, HBV and HCV markers were
      determined with ELISA method. Circulating immune complexes were determined with
      fotometer in the sediment of poliethilenglicol on 480 nm wavelength. Antigen-HAV
      in stool was prescribe through a method of reversed immunoelectroosmophoresis.
      Results of examination have shown that the persistence of IgM anti-HAV in sera of
      patients suffering from acute and prolonged form of disease was first of all
      continued and than discontinued. In male patients the IgM anti-HAV persistence
      significantly longer (p < 0.05) in prolonged phase, while in female patients the
      same goes for acute phase of disease. In prolonged HAV-infection persistence of
      IgM anti-HAV antibody is three times longer that in acute infection. IgM anti-HAV
      maintained in sera of patients three times longer than the persistence of sera
      aminotranspherasis activities and secretion of Ag-HAV in stool, which is
      proportional to the persistence of circulating immune complexes in sera of
      patients with acute and prolonged HAV-infection.

PMID- 15875470
TI  - [Prehypertension, hypertension and obesity types].
AB  - Aim of this study is to relate type of obesity with prehypertension and
      hypertension at 204 adult persons, both genders, age between 35-75 y. As a risk
      values of waist circumference were considered circumferences more than 94 cm at
      males and more than 80 cm at females. Obesity was less expressed in group of
      patients with prehypertension (BMI 25.8 +/- 4.4 kg/m2) compared with group of
      patients with hypertension (BMI 29.1 +/- 4.8 kg/m2). Blood pressure was
      positively correlated with obesity, especially with android type obesity. There
      was higher correlation of blood pressure with waist circumference, than with BMI.
      It is important to reduce overweight in a manner to prevent hypertension,
      especially at prehypertensive patients with android obesity.

PMID- 15875471
TI  - [Operative treatment of acute pancreatitis].
AB  - Most attacks of acute pancreatitis are self limiting, and the patients recover
      completely within days or weeks. In a few cases, however, the course is severe,
      with development of organ failure (single or multiple) and local complications
      such as necrosis, abscesses, and pseudocist. Between 01.01.2001-01.06.2004, 286
      cases of acute pancreatitis were treated in our clinic. The purpose of this study
      is to represent indication for operative treatment of acute pancreatitis and its
      complications, according to the Atlanta classification. According to our date,
      the most frequent cause are changes on biliary tract. Of these 286 patients, 247
      suffered from a mild or moderate type of acute pancreatitis and responded fully
      to medical treatment (215 patients) or to biliary tract surgery (32 patients).
      The hospital mortality of this group of patients was 2.4%. Surgery was indicated
      when the patients developed signs of an acute abdomen (9 patients), pancreatic
      pseudocyst (7 patients), progressiv icterus (2 patients), infection of pancreatic
      necrosis (10 patients), and pancreatic abscess (7 patients). Four patients with
      pancreatic necrosis were stable, and they had conservative treatment. The most
      difficult decision in the management of these patients is whether surgery is
      required and which of the complementary approaches to necrosectomy and drainage
      is appropriate. The hospital mortality of patients with severe acute pancreatitis
      was 28.2%. Multiple organ failure was the predominant cause of death.

PMID- 15875472
TI  - [Acute strong headache in emergency neurology (diagnostic and treatment)].
AB  - Acute, strong headache represent a frequent symptom with patients who report to
      the Emergency Neurology. Most of them have functional headaches from the group of
      primary headaches. However, a smaller number may have secondary headaches, due to
      structural changes of the cerebral parenchyma. Though the second group is
      considerably smaller, the secondary headaches, besides fast diagnostics require
      fast therapy, since they frequently imperil directly the patients life. The paper
      consider clinical and neurological predictions, indicating possible secondary
      headaches ("red flags") and diagnostic procedures, necessary to achieve their
      fast ethiological diagnosis. We consider also possibilities and limitations of
      certain additional methods (CT, cerebrospinal fluid examination, MR) with the aim
      to establish the examinations algorithm. Finally we offer procedures related to
      the therapy of acute primary as well as secondary strong headaches.

PMID- 15875473
TI  - [The neurologist role in diagnostics and therapy of the Alzheimer's disease].
AB  - Dementias represent nearly the most frequent diseases of the elderly population,
      out of which nearly 60% are related to the Alzheimer's dementia. According to the
      United Nations prognosis the number of patients suffering from this disease will
      raise from 25,5 million of cases, registered in 2000 up to 63 million in 2030,
      even 114 million in 2050. Therefore the recognition of this disease, earlier and
      exact treatment are substantially important both for the patient and the society.
      The treatment of this disease requires multidisciplinary approach. Thus we would
      like to focus on the neurologist role in this process.

PMID- 15875474
TI  - [Narrowing of lateral recesus in lumbal column (surgical treatment)].
AB  - INTRODUCTION: In this study was analyzed 49 persons with lumbar lateral recess
      stenosis who were treated by operation. Resection articular facets was main
      principe for decompression root of nerve in lateral recess region. After
      operation we noticed sings of recovory during next sixth mounts. Many study were
      wrote results of treatment lumbar spinal stenosis. Results of treatment central,
      lateral, lateral recess or foramina stenos is, were not announced. In this study
      we were analyzed intensity recovery neurological sings sixth mounts after
      operation lumbar lateral recess stenosis. METHODS: Diagnosis was establish after
      neurological examines, functional X-ray and CT of lumbar spine et
      electromyography lower extremities. We analyzed, also, and patients opinion about
      them condition and treatments. RESULTS: It was noticed good recovery of
      neurogenic claudication, paresthesic and pain in leg. Local pain in lumbar spine
      and damages sensibilities were significant presents after therapy. It was
      registered opinion of good recovery in high grade stenosis and stenois associated
      with disc protrusion. CONCLUSION: Nerve root decompression in stenotic lateral
      recess of lumbar spine could achieved removing part of hypertrophy artricular
      facets. Good recovery was achieved after operation and rehabilitations treatment.
      Some grade disability could stayed because damages snezibilitics and local pain
      in lumbar spine.

PMID- 15875475
TI  - [Congenital lobar emphysema].
AB  - BACKGROUND: Congenital lobar emphysema is characterized by overinflation of
      pulmonary lobe and is caused by localised bronchial obstruction. The disease may
      result in severe respiratory distress in early infancy. METHODS: Records of
      children, with congenital lobar emphysema, who were treated at our department
      between 1997-2003, were reviewed. RESULTS: Three males, aged 16 days till 1 year,
      were diagnosticed as congenital lobar emphysema. Presenting symptoms were dyspnea
      in 2 patients, cyanosis in 2 patients, wheesing in 2 patients, recurrent
      respiratory tract infection in 2 patients. Chest x rays and computerized
      tomography scans showed hyperinflation of the affected lobe in all patients. The
      affected sites were left upper lobe in 2 patients and right upper lobe in 1
      patient. All patients underwent lobectomy. CONCLUSION: It is necessary to suspect
      on this uncommon anomaly in early infancy. The diagnosis was established by chest
      x rays and CT scans. Intensive therapy and urgent lobectomy, in severe
      respiratory distress, are condition for successfully treatment.

PMID- 15875476
TI  - [The impact of secondary traumatization on the mental health of the patients with
      PTSD].
AB  - AIM: To determine the impact of secondary traumatization on the mental health of
      patients suffering from chronic PTSD. METHODS: This study involved two groups of
      subjects who were diagnosed with chronic PTSD. Group One is comprised of 41
      subjects who were included in treatment for the first time. Group Two is
      comprised of 13 subjects who were readmitted for treatment because of the
      reoccurrence of symptoms due to secondary traumatization. Both groups were
      assessed prior to treatment and after three months of treatment with a packet of
      standardized instruments that were chosen for this study by the authors. RESULTS:
      The authors present the results for the two groups of subjects; those from Group
      One who have showed for treatment for the first time, and those from Group Two
      who were readmitted to treatment after relapse of symptoms due to secondary
      trauma. Average results on assessment instruments for Group One were higher than
      those obtained for Group Two. CONCLUSIONS: Subjects suffering from PTSD who have
      received treatment in the past that yielded significant reduction in
      psychopathological symptoms have demonstrated milder deterioration in the course
      of the relapse due to secondary traumatization compared with the subjects who
      showed for treatment for the first time. In order to prevent reoccurrence of
      symptoms due to secondary traumatization in individuals suffering from PTSD,
      providing adequate social support and prevention of secondary traumatization is
      of utmost importance.

PMID- 15875477
TI  - [Epidemiological investigations transmisssion of Q fever among humans in Bosnia
      and Herzegovina].
AB  - Appearance of an acute disease by Coxiella burnetii in humans in Bosnia and
      Herzegovina is very big epidemiological problem because incidence rate is among
      the highest incidence rates in Europe. Incidence rate of Q fever in Federation
      Bosnia and Herzegovina was very high during 1998. year 5.68% and the highest in
      2000, with 115 diseases with acute clinical form of the disease and incidence
      rate of 6.95%. The incubation period varied from 9 to 28 days. Real incidence
      rate because of asymptomatic appearance of the disease is very much higher, at
      least 40-50 times higher. Chronic infection with Coxiella burnetii has been the
      most common developed as infectious endocarditis, which is the hardest
      complication. The researches of mode of transmission Q fever in humans showed
      that this disease spreads in epidemic and sporadic form in Bosnia and
      Herzegovina. In the period 1998-2003 year, there were 373 cases of Q fever, among
      them 265 or 71,05% cases epidemic transmission, and 108 or 28,95% cases sporadic.
      The research of outbreaks of Q fever showed that appearance of Q fever is
      statistical significant with risk factors at 266 cases of disease. The mode of
      transmission in 107 cases was the most probably across inhalation of infected
      aerosols.

PMID- 15875478
TI  - [Intramural hematoma in acute aortic syndrome].
AB  - Intramural haematoma is the precursor or the variant of a classical aortic
      dissection where hemorrhage occurs within the aortic wall (aortic media) and in
      absence of initial intimal tear. This entity looks like a classical aortic
      dissection, but it differs from it by its pathological characteristics. Although
      the intimal tear is absent, the prognosis of patients with intramural haematoma
      is similar to that of patients with classical aortic dissection; it is therefore
      very important for these patients to be early diagnosed. With a development of
      modern non-invasive diagnostical techniques the intramural haematoma is more
      often diagnosed and actually amounts at 10 to 30% of all acute aortic syndrome
      cases. Clinical characteristics and death rate of patients with intramural
      hematoma are similar to those of patients with classical aortic dissection,
      especially when it is obvious that there is a considerable risk for intramural
      haematoma to complicate into aortic ulcer, aortic aneurysm or rupture. Since
      intramural haematoma comprehensive diagnostic technique does not exist, safe
      therapy has not been yet established. Future randomized studies and serial
      observation of patients with intramural hemorrhage are indispensable not only to
      clarify these patients' survival predictors but also to define a model of optimal
      therapy.

PMID- 15875479
TI  - [Epidemiological and clinical characteristics of congenital anomalies in Tuzla
      Canton, Bosnia and Herzegovina].
AB  - AIM: of this work is to show epidemiological and clinical characteristics of
      congenital anomalies in Tuzla Canton, Bosnia and Herzegovina. MATERIALS AND
      METHODS: Retrospective analysis of 41 395 labours in Ob & Gyn Clinic University
      Clinical Centre, Tuzla, from Jan 1995 to Dec 2003. Diagnosis of congenital
      anomalies was performing on the basis of clinical, ultrasound examination, CAT
      scan and cariotype. RESULTS: In the eight years period we have registered 647
      live born both genders with congenital anomalies on the birth, with incidence
      1:63.97 and prevalence 15.62 on 1000 live born. Most frequently we had hearth
      congenital anomalies (22.10%) with prevalence of 3.45%. Chromosomal aberrations-
      Sy Down we had in 83 cases with incidence 1:498.7. Age structure of mothers was
      between 16 to 42 years, with average age 29,85 (SD +/- 2). Sufficient but not
      optimal number of controls during pregnancy (8-10) we have only in 8.19% of
      mothers. Rate between genders was 1:1,27 in favour of female newborns which is
      significantly different from general population with rate 1,08-1 in favour of
      male newborns in Tuzla Canton. We have a few options for operative treatment
      (5.71%) especially in centres with low possibilities for postoperative care and
      therapy and consequently high mortality (25.96%). CONCLUSION: Congenital
      anomalies are great problem for health care in Tuzla Canton, so we urge to
      salvation of this problem at the state level.

PMID- 15875480
TI  - [Prolapse and herniation of abdominal organs into the thoracic cavity as a
      diagnostic problem in pulmonology].
AB  - In this case report it was shown five cases of passing abdominal organs in
      thoracic cavum. All of them were women more than 70 years old with symptoms of
      respiratory illnesses. Their chest-X ray has shown various shadows. They had a
      long antibiotic treatment in outpatient department before sending to hospital
      under suspicion of lung or mediastinal tumor. Two of them had anamnesis of trauma
      a few years ago. All of them had no bronchoscopic intrabroncial changes, two had
      signs of extramural bronchial compression. All of them had different level of
      ventilatory insufficiency, with normal laboratory findings, some of them had
      positional EKG changes. By different diagnostic procedures: chest X-ray,
      bronchoscopy, gastrointestinal X-ray with contrast, computer thomography of
      thorax, we found: 2 cases of large hiatal hernia, 1 case of prolapsus whole
      ventricle in mediastinum, 2 cases of passing ventricle and large part of
      intestines in thorax. All of them rejected proposed abdominal surgery treatment.
      We appoint the importance of this appearance to avoid wasting time in appointing
      the diagnosis, to avoid different diagnostic procedures and long lasting
      antibiotic treatment, and prevent complications, first of all incarceration of
      organs.

PMID- 15875481
TI  - [Cavernous transformation of portal vein].
AB  - Cavernous transformation of the portal vein occurs with long-standing portal vein
      thrombosis (PVT) because of the development and dilatation of multiple small
      vessels in and around the recanalising main portal vein. Thrombosis and occlusion
      of the portal vein leads to portal hypertension with enlarged spleen and the
      development of porto-systemic collaterals. The main clinical presentation is
      gastroesophageal variceal bleeding and hematologic abnormalities due to
      splenomegaly (hyperspleenismus-pancytopenia). We described the young patient with
      splenomegaly and extensive cavernous transformation of portal vein. The patient
      had thrombosis portal vein in early childhood and massive bleeding from large
      oesophageal varices at age 13. Full clinical evaluation is required because of
      abdominal pain. The liver is histologicaly and functionally normal. Diagnosis of
      cavernous transformation of the portal vein is confirmed by abdominal
      ultrasography, color Doppler ultrasonography and CT angiography.
      Oesophagogastroscopy reveals almost complete reduction of oesophageal varices,
      but confirms portal gastropathy as a source of patient's complaints. Natural
      course of PVT in this patient shows possibility of full reduction of oesophageal
      varices, but still the presence of different consequences of portal hypertension.

PMID- 15875482
TI  - [Sympathetic ophthalmia as complication of perforated wound of the eye].
AB  - Symphatetic uveitis was a fairly common and described disease in 19th century.
      Many cases of bilateral blindncss associated with injury and inflammation were
      diagnosed as sympathetic ophthalmia. A penetrating wound appears to be essential
      for the development of symphathetic ophthalmia. Since the antigen-presenting
      cell, of the eye appear to be functionally suppressed in situ, these antigens
      normaly would produce an inactivation signal. Authors present a case of 7 years
      old boy, who had injury of the right eye in the school. We performed surgery, but
      that right eye after several months went to subatrophy. Three months later, he
      come again with problems in left eye. We diagnosed symphatetic ophthalmia and
      included high doses of steroids. Two years after he is still on high dose of
      steroids due to two times of egxazcrbation. A month ago we perfomed
      phacoecmulsofication cataract syrgery, because a cataract developed due to high
      doses of steroid therapy.

PMID- 15875483
TI  - [Morbus Albers Schonberg osteopetrosis].
AB  - The patient presented has bone disease, so called "mramor disease". The disease
      is characterized by insuffiticnty of ostcoclasts which results n persisting of
      primary spongiosis without normal eroding and bone rebuilding. The discase is
      diagnosed by X rays where the bone density is increased. The medular space is
      completly closed by dense bone knitting which, with soft cortical space, seems
      like bone in bone. This is autosomal recessive disease with serious clinical
      picture in infants.

PMID- 15875484
TI  - [Rehabilitation of the patient with cerebrovascular insult with haemorrhage--case
      study].
AB  - This is case study of the patient, 58 years old, occupation merchant, admitted
      tot he neurological clinic as urgent case with the following diagnosis: insultus
      cerebrovascularis per haemorrhagiam, Haemathoma cerebrale reg. temporoparietalis
      lat. sin., Aphasia sensomotoria, Hemiplegia cerebralis lat. dex, Hypertensio
      art., Cor hypertonicum comp., Status post nephrectomiam lat. dex. After 26 days
      the patient was moved to the Institute for physical medicine and rehabilitation
      where started rehabilitation treatment in which was included speech therapist as
      well. After 30 days,movement of right side was improved very well, especially of
      the patient's leg, and patient began to walk helped by stick. In the same time,
      the speech was improved, and we concluded that in rehabilitation of this kind of
      patients, team work is necessary, and we think that speech therapist should be
      included as early as possible with maximal involvement of the family.

PMID- 15875485
TI  - The contributions of the right and left hemispheres of the brain to the
      polymorphism and heterogeneity of pyramidal syndrome.
AB  - This study was conducted to address the clinical and neurophysiological features
      of pyramidal syndrome in patients with lateralized hemispheric lesions. A total
      of 52 patients were studied, all with hemiparesis following acute cerebrovascular
      accidents of the ischemic type in the right (24 patients) or left (28 patients)
      hemispheres of the brain. Clinical neurological analysis was performed, along
      with transcranial magnetic stimulation, evoked abdominal reflexes, movement
      associated motor potentials, and somatosensory evoked potentials. Lesions of the
      right hemisphere resulted in significant weakening of activatory influences at
      both the hemisphere level and on descending motor structures, with marked
      impairment of the afferent flow from both sides of the body and excessive
      disorganization of activity in the left, "presumptively healthy," side. Left
      sided pathology impaired efferent control not only of the contralateral, but also
      of the ipsilateral side of the body. These data identify different
      neuroanatomical and neurophysiological features of the cerebral hemispheres not
      only in healthy people, but also in pathological conditions, this probably
      accounting for the polymorphism and heterogeneity of pyramidal syndrome in
      patients with lateralized cerebral lesions.

PMID- 15875486
TI  - A model of attention and memory based on the principle of the dominant and the
      comparator function of the hippocampus.
AB  - The six major questions of attention are described in terms of the dominant, as
      defined by Ukhtomskii. The dominant was in turn simulated as a systems
      manifestation of phase transitions in the brain. The theoretical and experimental
      bases for the existence of metastable states in the brain are reviewed, these
      states having lifetimes of 1 sec and more. This approach simultaneously provides
      solutions for all the major questions of attention and the "central controller."
      A neurobiological model of attention and memory is proposed, based on the systems
      properties of Ukhtomskii's dominant and the comparator function of the
      hippocampus as described by Vinogradova. New published data are presented to
      support the existence of an information processing system in the brain in which
      the hippocampus plays the central role.

PMID- 15875487
TI  - Diffusional extrasynaptic neurotransmission via glutamate and GABA.
AB  - Glutamate and GABA are the main synaptic neurotransmitters in the hippocampus.
      However, their actions are not limited only to the local postsynaptic zone. These
      amino acids can be released into the extrasynaptic space by glutamate and GABA
      reuptake, glial exocytosis, osmotic shock, and spillover (flowing out of the
      synaptic cleft). Glutamate and GABA receptors are also located on various parts
      of neurons and glial cells. Depending on the subcellular distribution of these
      receptors, their subunit composition, and the matabotropic/ionotropic functions,
      the effects of extracellular glutamate and GABA differ. The present review
      discusses the general principles of the organization of diffusion-based
      glutamatergic and GABAergic systems of extrasynaptic neurotransmission, the
      interaction of these systems with synaptic transmission, and the interaction of
      diffusion signals with each other.

PMID- 15875488
TI  - Characteristics of the development of the sensorimotor cortex in rats aged 7-8
      days in roller cultures of free-floating brain slices.
AB  - The development and formation of the neuronal architectonics of organotypic
      structures of the sensorimotor cortex in rats aged 7-8 days were studied in
      roller cultures. Free-floating slices were cultured for 2-3 weeks. Serial
      paraffin sections of cultured tissue were stained with fast cresyl violet as
      described by Nissl. Initially planar sections of the cortex were found to change
      their configuration during the process of cultivation and were transformed into
      spherical structures, retaining the major histotypic features of cortical
      formations. Radially orientated pyramidal cells and fusiform neurons formed a
      cortical rudiment, not discriminated into layers, over the whole surface of the
      spherical tissue structures. In free-floating slices of the sensorimotor cortex
      of rats aged 7-8 days in roller cultivation, histogenetic processes continued,
      leading to the formation of histotypic cortical structures similar to the
      phylogenetically more ancient allocortical formations of the forebrain.

PMID- 15875489
TI  - NADPH-diaphorase-positive cells in the thalamic nuclei and internal capsule in
      humans.
AB  - The nuclei of the dorsal thalamus and reticular nucleus in humans were found to
      contain separated NADPH-diaphorase (NADPH-d)-positive neurons. Staining of NADPH
      d-positive neurons and all their processes, along with previous studies of
      neurons in the nuclei of the dorsal thalamus based on the Golgi method, allowed
      the type of these cells to be identified as sparsely branched. The main, densely
      branched, efferent neurons did not contain NADPH-d. NADPH-d-positive neurons
      included reticular cells and cells of one of the types of short-axon
      interneurons. The internal capsule contained large numbers of NADPH-d-positive
      reticular neurons. NADPH-d-positive neurons were found in contact with vessels.
      Thus, NADPH-d-positive cells of the dorsal thalamus, reticular nucleus, and
      internal capsule were evolutionarily more ancient and less structurally complex
      cells.

PMID- 15875490
TI  - Impairments in working memory and decision-taking processes in monkeys in a model
      of Alzheimer's disease.
AB  - Studies were performed on two groups of animals (three monkeys in each). Monkeys
      of group I received unilateral intracerebroventricular injections of the
      neurotoxin p75-saporin (the ribosomal toxin saporin bound to monoclonal antibody
      to the p75NTR receptor), which elicits irreversible degradation of cholinergic
      neurons in the basal nuclei of Meynert, along with the enzyme dopamine-beta
      hydroxylase (DBH-saporin), which impairs the functioning of noradrenergic neurons
      in the locus ceruleus. Monkeys of group II received injections of sterile
      physiological saline (0.9% NaCI). Monkeys were trained to discriminate stimuli
      containing different types of information (spatial frequency grids, geometric
      figures with different colors, different spatial relationships between objects)
      and perform spatial selection. The characteristics of working memory were
      identified in delayed differentiation tasks in monkeys of both groups before and
      after injections. These studies provided the first evidence that the development
      of Alzheimer's disease in rhesus macaques is characterized by a deficiency of
      working memory, this being based on impairment of two components of these
      processes. Impairment of the first in monkeys of group I was minifest in delayed
      visual differentiation as a significant decrease in correct responses. The extent
      of decreases depended on the duration of the delay and the type of visual
      information. Impairment of the second component, associated with decision-taking
      processes, was characterized by an increase in refusals to take decisions and was
      independent of the duration of delays and the type of visual information. Monkeys
      given injections of physiological saline showed no significant differences in
      these characteristics. The features of impairments in these memory components
      resulting from the development of Alzheimer's disease demonstrate that the
      structural-functional organization of cholinergic and noradrenergic mechanisms
      responsible for sensory processing differ from those involved in decision-taking.

PMID- 15875491
TI  - Formation of locomotor patterns in decerebrate cats in conditions of epidural
      stimulation of the spinal cord.
AB  - Acute experiments on decerebrate cats were performed to study the mechanism of
      formation of the locomotor pattern in conditions of epidural stimulation of the
      spinal cord. These studies showed that only segments L3-L5 contributed to
      generating the stepping pattern in the hindlimbs. At the optimum frequency (5-10
      Hz) of stimulation of these segments, formation of electromyographic burst
      activity in the flexor muscles was mainly due to polysynaptic reflex responses
      with latencies of 80-110 msec. In the extensor muscles, this process involved the
      interaction of a monosynaptic reflex and polysynaptic activity. In epidural
      stimulation, the stepping pattern was specified by spinal structures, while
      peripheral feedback had modulatory influences.

PMID- 15875492
TI  - Control of fine movements mediated by propriospinal neurons.
AB  - Studies of the role of the C3/C4 propriospinal system of spinal cord interneurons
      in the control of fine movements and the processes compensating motor deficiency
      after lesioning of the cortico- and rubrospinal tracts at the level of segments
      C2 and C5 were studied in cats. These experiments showed that after lesioning of
      the cortico- and rubrospinal tracts at the level of C5, the C3/C4 propriospinal
      system played a key role in recovery processes, while after lesioning at the
      level of C2, the leading role was played by ipsilateral tracts in the ventral
      part of the spinal cord. In addition, the propriospinal system demonstrated a
      significant level of plasticity and was able to provide complete control of a
      number of fine voluntary movements.

PMID- 15875493
TI  - The effects of 6-hydroxydopamine on the electrical characteristics of snail
      neurons in long-term sensitization.
AB  - The effects of the neurotoxin 6-hydroxydopamine on the formation of long-term
      sensitization and changes in the membrane characteristics of identified neurons
      were studied. Injections of the neurotoxin 6-hydroxydopamine blocked the
      acquisition of long-term sensitization; when neurotoxin injections were given
      after the formation of long-term sensitization, they had no subsequent effect on
      conduction parameters. At the cellular level, recording of the electrical
      characteristics of common snail defensive behavior command neurons (LPa3, RPa3,
      LPa2, and RPa2) showed that the effects of 6-hydroxydopamine consisted of a small
      depolarization shift in the membrane potential and a change in the action
      potential generation threshold. Formation of long-term sensitization after
      injections of 6-hydroxydopamine did not lead to further decreases in the membrane
      and threshold potentials of command neurons as compared with snails only given
      injections of 6-hydroxydopamine. The changes in electrical measures of command
      neurons induced by administration of the neurotoxin 6-hydroxydopamine lasted at
      least two weeks.

PMID- 15875494
TI  - The effects of L-DOPA and transcranial magnetic stimulation on behavioral
      reactions in kindled rats.
AB  - Acute experiments were performed on rats to produce a model of chronic epileptic
      activity--pharmacological kindling by repeated doses of picrotoxin (1.0-1.2
      mg/kg, i.p.). During the early period following kindling (24 h from the last dose
      of epileptogen), animals showed decreases in measures of investigative behavior
      as measured in an open field test, along with reductions in sexual and feeding
      behavior. The severity of these impairments had decreased by two weeks from the
      last picrotoxin dose. Both treatment with L-DOPA (100 mg/kg, i.p.) and
      transcranial magnetic stimulation (20 impulses with induction, peak 1.5 T) were
      accompanied by increases in measures of investigative, sexual, and feeding
      behavior in the animals, suggesting that mechanism of action of transcranial
      magnetic stimulation in relation to kindling-induced behavioral abnormalities is
      mediated by activation of the dopaminergic system of the brain.

PMID- 15875495
TI  - Separate training of hemispheres to perform visual discrimination in conditions
      of blocking of interhemisphere transmission by masking.
AB  - Subjects were trained to discriminate three figures presented in the left field
      of vision and three other figures presented in the right field of vision. In
      these conditions, the two hemispheres usually show identical learning to
      discriminate the sets of stimuli because the hemispheres in healthy humans can
      exchange information. In the present study, training was performed in conditions
      in which, during presentation of stimuli, the opposite visual hemifield was
      covered by a mask. After training, the recognition of all six figures was
      compared by presenting them to the left and right visual fields. Each hemisphere
      recognized figures presented to the cognate hemifield but completely or very
      nearly failed to recognize figures learned by the other hemisphere. The mask
      would thus appear to block (completely or partially) the transmission of
      information from one hemisphere to the other. Thus, it was possible to train the
      hemispheres separately to recognize different sets of images in healthy subjects.

PMID- 15875496
TI  - Detection of narrow bars when presented in the right and left visual hemifields.
AB  - Three series of psychophysical experiments were performed to study the effects of
      additional images on the contrast thresholds for detection of narrow bars of
      width 1 arc min and length 1 arc degree presented randomly to the left and right
      sides of the fixation point with an eccentricity of 4 degrees. The additional
      images were bars of the same size but with lower contrast, presented to the right
      and left of the test bar at varying distances, i.e., 1-2 degrees. Different
      series used different contrast ratios for the test and additional bars. The first
      series revealed significant predominance of one visual hemifield over the other
      in performing the bar detection task, though the predominant side varied in
      different subjects. This predominance disappeared or changed to the opposite side
      in the second or third series. There was a tendency for the additional images to
      have asymmetrical influences on the detection threshold for the test bar:
      additional bars had more extensive inhibitory influences when they were on the
      peripheral side of the test bar. These data provide evidence for the absence of
      specificity in hemisphere operation in the detection task. The mechanism of
      description of peripheral images is discussed.

PMID- 15875497
TI  - [An alarming problem in the therapy of infective endocarditis: the development of
      antibiotic-resistant strains].
AB  - We shall focus on infective endocarditis due to Enterococcus spp and
      Staphylococcus aureus, both able to develop resistance to antibiotics with
      different mechanisms. Vancomycin-resistant strains produce some of the most
      challenging nososocomial infections. Enterococci develop resistance practically
      to all classes of antibiotics. Vancomycin-resistant strains, in the '90s, passed
      from 2% to more than 25%. Five types of vancomycin-resistance were reported (from
      van A to van E), linked to the presence of certain classes of genes regulating
      the production of abnormal precursors of peptidoglycan which inhibit the action
      of vancomycin. Staphylococcus aureus is a fearful organism whose infections can
      reach a mortality rate of 80%. In 1943, as soon as penicillin G was introduced
      into therapy, Staphylococcus strains producers of beta-lactamase were identified.
      After beta-lactamase-resistant penicillins were introduced into therapy,
      methicillin-resistant Staphylococcus strains appeared in the '60s. In 1996 the
      first strain of methicillin-resistant and vancomycin-resistant Staphylococcus
      aureus was isolated. In 2001, in Japan, the first case of infective endocarditis
      due to Staphylococcus aureus resistant to methicillin and non-responsive to
      vancomycin was described. The resistance is connected to an increased synthesis
      of the cell wall, which thickens reducing the activity of vancomycin.

PMID- 15875498
TI  - [New etiologies responsible for infective endocarditis with negative blood
      cultures].
AB  - The prevalence of infective endocarditis with negative blood cultures varies in
      the different series from 5 to 25%. There are certain explanations of negative
      blood culture endocarditis: previous incorrect antibiotic therapy before
      obtaining blood samples (antibiotic treatment inhibits the growth of germs, and
      therefore bacteremia, without sterilizing the vegetations); infective
      endocarditis due to fastidious microorganism, that is of difficult cultivation
      and identification; infective endocarditis due to cell-dependent organism (e.g.
      Coxiella burnetii); infective endocarditis due to fungi; non-infectious
      involvement of the endocardium (at times with vegetations) during the course of
      certain disease. We underline three etiologies (Coxiella burnetii, Bartonella
      species and Whipple's disease bacterium) because their study have constituted the
      stimulus for the introduction into clinical evaluation of patients with suspected
      infective endocarditis of different diagnostic approaches, based on a correct
      sequential application of blood cultures, serodiagnosis and molecular
      microbiology.

PMID- 15875500
TI  - [Drug-eluting stents: from the results of clinical studies to economic simulation
      models in the Italian reality].
AB  - Several studies with drug-eluting stents (DES) have demonstrated dramatic
      reductions in restenosis rates compared with bare metal stents (BMS). Although
      the clinical benefits of DES are increasingly evident, important concerns about
      their costs have been raised. Most data regarding the impact of restenosis on
      long-term costs after percutaneous coronary intervention (PCI) are derived from
      clinical trials. These studies demonstrate that there is no single cost or
      economic burden of restenosis; these values vary substantially according to the
      specific patient population under investigation and to the healthcare system
      reality where they are applied. In the present study we propose an economic
      interactive decision model which was applied to the Italian healthcare system,
      considering the different reimbursement rates of the Italian regions for DES and
      for both PCI and coronary artery bypass surgical interventions (CABG). The aim of
      this model was to simulate the impact of DES introduction after potential
      complete reimbursement by the national healthcare system, hypothesizing the usage
      of 1.4 stent per patient in case of single vessel disease and 2.4 stents in case
      of multivessel disease, and utilizing the TAXUS IV rate of revascularization for
      reintervention costs calculation and the ARTS-I study for CABG costs. For a low
      risk patients' population, the mean cost of a procedure with DES was 6% greater
      than utilizing BMS (xi 8125 for DES vs xi 7651 for BMS). However, this percentage
      was reduced in case of diabetic patients (+4%), long lesions (+2%) and was
      favourable for small vessels (-3%). In addition, in case of multivessel disease
      with conversion from CABG to DES, the 12 months cost per patients was reduced of
      around 30% (xi 10 170 for PCI vs xi 14 584 for CABG). This model suggests that
      national healthcare system may save 2.1% of the total costs (xi 18.60 millions)
      if 60% of revascularization procedures converts to total DES utilization and 15%
      from CABG to PCI with DES.

PMID- 15875499
TI  - [Atrial septal aneurysm: a true embolic source?].
AB  - Atrial septal aneurysm (ASA) is a well-recognized cardiac abnormality of
      uncertain clinical significance. It has early been reported as an unexpected
      finding during autopsy, but it may also be diagnosed in living patients by
      echocardiographic techniques. An association between ASA and focal cerebral
      ischemic events has been suggested. Nevertheless, the role of ASA as a risk
      factor for cerebral ischemia is poorly defined. Several studies have demonstrated
      a significantly higher proportion of ASA in the patients referred for
      transesophageal echocardiography after a cerebral ischemic event of unknown
      cause. However, ASA is often associated with other cardiac abnormalities such as
      patent foramen ovale, atrial septal defects, as well as mitral valve prolapse or
      atrial arrhythmias. Due to the fact that these abnormalities are also possible
      sources of cardiac emboli it is even more difficult to assess the embolic
      potential of an ASA, independently. In this review, we have examined most of the
      papers on this topic to try to define the prevalence of ASA in the stroke
      patients and how this abnormality could be a risk factor for recurrences of
      cerebrovascular events.

PMID- 15875501
TI  - [Late pacemaker pocket erosion: epidemiologic analysis in a region of North
      Western Italy (Piedmont and Valle d'Aosta)].
AB  - BACKGROUND: Pacemaker pocket erosion is still a relevant clinical problem as it
      may be the cause of septicemias and/or endocarditis with consequent poor
      prognosis. The true incidence of this complication is rather variable in the
      various series of cases reported in the literature ranging between 0.9 and 5%
      when early infective complications are included. METHODS: In order to evaluate
      the real incidence of this complication we performed a retrospective analysis on
      the data coming from all the pacemaker implanting centers in Piedmont. Data
      collection forms were completed for each patient presenting this kind of
      complication from 1996 through 1998; the follow-up lasted for at least 36 months.
      RESULTS: In the 21 centers (81% of all implanting centers in Piedmont) in which
      completed data were collected, 7793 pacemaker and 289 automatic cardioverter
      defibrillator (ICD) implants were performed. During the follow-up 100 cases of
      pacemaker pocket erosion were observed with a total incidence of 1.28% (range 0
      3.1%); no cases of ICD pocket erosion were reported. Diabete mellitus was the
      most frequent associated disease (25% of patients), about 30% of patients were
      taking antiplatelet drugs. The kind of surgical procedure performed to resolve
      the problem was different in the various centers according to personal experience
      and to the various evaluations performed by each physician. CONCLUSIONS: Our
      study demonstrates that the overall incidence of late pacemaker pocket erosion in
      our region is absolutely acceptable even in spite of relevant differences in the
      various implanting centers. A system of continuous monitoring with the data
      collection of all the performed procedures would be extremely useful to
      constantly check the quality level both locally and regionally.

PMID- 15875502
TI  - [Telecardiology in the management of acute myocardial infarction: the experience
      of the provincial network of Mantova].
AB  - BACKGROUND: Since June 2001 we activated a program for the treatment of acute
      myocardial infarction, based on the early assessment of the patient's risk
      profile, on telematic connection among care centers and optimization of critical
      pathways for access to care. The aim of this work was to assess the effectiveness
      of telemedicine in the reduction of time to treatment. METHODS: Mantova, a
      province of eastern Lombardy (northern Italy) is provided with one single
      sanitary district with one (tertiary hospital) referring hospital equipped with a
      cath lab on call 24/24 hours for primary coronary angioplasty (PTCA) and cardiac
      surgery and 6 community hospitals: 2 with coronary care units, 2 with a
      cardiology section, and 2 rehabilitation hospitals. The emergency medical system
      transport, activated 24/24 hours, consists of 6 advanced life support (ALS)
      ambulances and 11 basic life support (BLS) ambulances (2 with trained nurse
      staff). Each ALS ambulance is equipped with a semiautomatic defibrillator
      LIFEPACK 12 coupled with cellular telephone GSM transmission of the 12-lead ECG.
      RESULTS: In the first 3-year activity of the project 340 patients with acute
      myocardial infarction underwent primary PTCA: 248 (73%) referred to first aid of
      the nearest hospital reached either by BLS ambulance or by their own means of
      transport and were hence transferred to the referring hospital for primary PTCA
      (group A), while 92 patients (27%) were aided at their own house by ALS
      ambulances and, after transmission of the 12-lead ECG to the referring coronary
      care unit, were directly transferred to the cath lab (group B). Decisional delay
      was 144 +/- 65 min in group A while 74 +/- 37 min in group B. Mean door-to
      balloon time was 76 +/- 26 min in group A and 47 +/- 21 min in group B. High
      incidence of post-procedural TIMI 3 flow was achieved in both groups. In-hospital
      mortality was 6.8% in group A e 5.4% in group B. CONCLUSIONS: Our data show that
      patients referring directly to ALS ambulances had a lower decisional delay.
      Transmission of the patient's ECG and clinical parameters allows an early and
      accurate diagnosis and assessment of the individual risk profile with a
      consistent reduction in time to treatment and positive effects on the mortality
      rate.

PMID- 15875503
TI  - [Risk factors, life habits and personal beliefs of nurses and nurse-students
      about cardiovascular prevention].
AB  - BACKGROUND: The contribution of conventional factors (hypertension, dyslipidemia,
      diabetes mellitus and smoke) to the risk of development of atherosclerotic
      cardiovascular disease is known. Nurses have a strong role in helping patients
      improve their risk profile, and change their lifestyle. Behaviors and beliefs of
      the nurses (and physicians as well) are relevant to their "reliability" as models
      and educators. METHODS: A questionnaire was administered to a cohort of 98
      students attending the last course-year in a school of nursing, and to a cohort
      of 84 nurses working in a cardiovascular department, to investigate their
      awareness of their own risk factors, their lifestyle, and their attitudes as to
      the primary prevention of cardiovascular disease. RESULTS: Among heritable risk
      factors, hypertension ranked first in the awareness of both students and nurses,
      but the risk inherent in a family history of sudden death and early myocardial
      infarction was recognized only by 36% of subjects. Smokers were more frequent
      among students than among nurses (40 vs 25%); in both cohorts the misconception
      was common among smokers, that "light" cigarettes or smoking "no more than 5-10
      cigarettes per day" is not harmful (15 and 30% of responders, respectively). The
      knowledge of upper normal limits for blood pressure, plasma cholesterol and
      triglycerides was often poor in both cohorts. CONCLUSIONS: The knowledge and
      awareness of risk factors and harmful life habits should be improved by stressing
      their importance to the nurse students with a high priority during the school,
      and to the practicing nurses during postgraduate courses. This may be especially
      important for smoking. On the whole, however, our data suggest that the majority
      of the interviewed subjects, especially among the nurses, have a lifestyle that
      is a credible model for our patients.

PMID- 15875504
TI  - [Acute myocardial infarction after wasp sting without anaphylactic reaction].
AB  - Bites of hymenopterans (bees, wasps and hornets) are very frequent phenomena that
      can stir up allergical reactions in venom-susceptible patients but that seldom
      provoke acute myocardial infarction. In the literature we can find case reports
      of myocardial infarction after bites of hymenopterans, and preceded by an
      allergic reaction (sometimes with angiographic evidence of undamaged coronary
      arteries). The pathophysiological determinant seems to be related to the chemical
      composition of hymenopterans venom, basically made up by vasoactive and
      thrombogenic substances able to create vasospasm and coronary thrombosis. Our
      report refers to a 65-year-old male patient without prior cardiological and
      allergic events who, bitten by a sharm of three bees, complains of an acute large
      anterior myocardial infarction with angiographic evidence of thrombotic lesion of
      the proximal left anterior descending artery treated with direct stenting with
      procedural success, without showing allergical symptoms. The pathophysiological
      determinant seems to be related to the release of vasoactive amines and
      thrombogenic substances contained into the hymenopterans venom, the former able
      to produce vasospasm, the latter able to create diffuse thrombosis. The use of
      adrenaline itself to counteract the possible systemic allergic reaction appears
      to advise against the treatment of patients with cardiological symptoms or
      coronary artery disease and because of its strong vasoactive activity (it leads,
      in fact, to vasoconstriction) and thrombogenic effects.

PMID- 15875505
TI  - Antiarrhythmic drugs in patients with recurrent atrial fibrillation: where are
      we?
AB  - In patients with recurrent atrial fibrillation (AF), the hallmark of treatment
      has long been the use of antiarrhythmic drugs. The following strategies are
      available: a) any antiarrhythmic treatment; b) out-of-hospital episodic treatment
      ("pill-in-the-pocket" approach); c) prophylactic antiarrhythmic therapy; and d)
      hybrid therapy. The following patients with recurrent AF should not undergo any
      antiarrhythmic therapy: after the first AF episode; patients with rare,
      hemodynamically well-tolerated and short-lasting (a few hours) AF episodes;
      patients with perioperative AF, without history of recurrent AF; patients with AF
      during acute myocardial infarction or other acute diseases, without history of
      recurrent AF; and "holiday heart" syndrome. In patients with infrequent AF
      episodes (< 1 per month) and hemodynamically well-tolerated, but long enough to
      require emergency room intervention or hospitalization, a good treatment might be
      the "pill-in-the-pocket" approach, consisting of a single-dose oral ingestion of
      flecainide or propafenone at the time and place of palpitation onset. A recent
      Italian study has shown that this treatment is effective and safe. When AF
      episodes are frequent and/or hemodynamically badly tolerated, the treatment of
      choice is the prophylactic therapy with antiarrhythmic drugs. When these drugs
      fail (ineffective or not tolerated) a non-pharmacological treatment or a hybrid
      therapy may be indicated.

PMID- 15875506
TI  - Non-antiarrhythmic drugs for the prevention of cardiac arrhythmias.
AB  - It is noteworthy that drugs having a significant impact in preventing arrhythmias
      (atrial or ventricular) are those with no direct specific antiarrhythmic
      electrophysiologic properties. Specifically, drugs able to interfere with the
      renin-angiotensin system and the n-3 fatty acids seem to play a relevant role as
      antiarrhythmics, even if they do not act in the typical manner. Angiotensin
      converting enzyme (ACE) inhibitors decrease the incidence of arrhythmias in
      patients with decreased left ventricular function. The main reduction is linked
      to a decrease of ventricular arrhythmias, while several studies have suggested
      that ACE-inhibitors may also decrease the burden of atrial fibrillation.
      Furthermore, many of angiotensin receptor blockers and spironolactone have been
      shown to have antiarrhythmic properties. n-3 polyunsaturated fatty acids (PUFAs)
      are known to be antiarrhythmic as well. Their effects on the fast voltage
      dependent sodium current I(NA), inhibition of I(Ca2+) and the K+ channel
      modulation explain their antiarrhythmic properties. For these reasons the renin
      angiotensin system blockade and the n-3 PUFA intake may provide simple and safe
      protection from cardiac arrhythmias.

PMID- 15875507
TI  - Non-invasive sudden death risk stratification.
AB  - Most sudden cardiac deaths are caused by fatal ventricular arrhythmias
      (ventricular tachycardia [VT] and fibrillation) in patients with and without
      known structural heart diseases. Given the large number of patients potentially
      at risk for developing ventricular arrhythmias, any strategy for treating them
      prophylactically requires efficient and effective risk stratification. Both non
      invasive and invasive testing may be used for prognostic evaluation of patients
      with heart diseases. The optimal way to use them in the risk stratification for
      sudden cardiac death will depend in part on the goals of screening. At present
      risk markers perform better at identifying low-risk patients who may not need an
      implantable cardioverter-defibrillator (ICD), because all tests have a high
      negative predictive accuracy. In our opinion an electrophysiological test should
      not be performed and an ICD should not be implanted in post-myocardial infarction
      patients with moderate left ventricular dysfunction (left ventricular ejection
      fraction 30-40%) with a preserved autonomic balance and without non-sustained VT.
      In MADIT II-like patients electrophysiological testing does not seem necessary
      and an ICD could not be implanted only in patients with a negative T-wave
      alternans test. Most of the data available refer to patients with ischemic
      cardiomyopathy but the preliminary data on T-wave alternans suggest its
      usefulness in patients with non-ischemic cardiomyopathy too, although a large
      definitive study has not yet been completed in this important population.

PMID- 15875508
TI  - Atrial fibrillation ablation.
AB  - Radiofrequency catheter ablation is currently used widely and successfully to
      treat a variety of arrhythmias, and ablation for atrial fibrillation represents
      the frontier of arrhythmia research. Development in many areas will offer to the
      electrophysiologic community a more rational and effective background upon which
      select patients for ablation and identify the optimal ablative strategy. Among
      mechanisms recognized for having a role in atrial fibrillation stay pulmonary
      vein focal triggers, rotor at the pulmonary vein-left atrial junction, a critical
      mass to sustain fibrillatory conduction and vagal ganglia. The latter represents
      the frontier of research as with new technologies based on magnetic resonance
      imaging they could be easily and specifically identified and targeted for
      ablation. It is fundamental that both CARTO and NavX systems are currently
      investigating integration with magnetic resonance imaging to reconstruct the left
      atrium. Furthermore a learning curve effect can be abated with the use of new
      systems for the remote control of the catheter such as stereotaxis. In the last
      decade, we empirically devised a technique that is both safe and effective for
      curing atrial fibrillation. Briefly, using a three-dimensional mapping system,
      either CARTO or NavX system, we reconstruct the left atrium and the pulmonary
      ostia; thereafter circumferential ablation lines are normally created starting at
      the lateral mitral annulus and withdrawing posterior then anterior to the left
      sided pulmonary veins, passing between the left superior pulmonary vein and the
      left atrial appendage before completing the circumferential line on the posterior
      wall of the left atrium. The right pulmonary veins are isolated in a similar
      fashion, and then a posterior line connecting the two circumferential lines on
      the roof is performed to reduce the risk of macroreentrant atrial tachycardias.
      The endpoint for circumferential ablation is a > 70-90% reduction in voltage
      within the isolated regions. In this article we sought to describe critical
      methodological aspects of our techniques along with future implementation with
      new technologies and to summarize our published clinical experience on the most
      prestigious journals.

PMID- 15875509
TI  - Atrial tachyarrhythmia prevention and treatment by means of special pacing
      algorithms.
AB  - Pacing prevention algorithms have been introduced in order to maximize the
      benefits of atrial pacing in atrial fibrillation prevention. It has been
      demonstrated that algorithms actually keep overdrive atrial pacing, reduce atrial
      premature contractions, and prevent short-long atrial cycle phenomenon, with good
      patient tolerance. However, clinical studies showed inconsistent benefits on
      clinical endpoints such as atrial fibrillation burden. Factors which may be
      responsible for neutral results include an already high atrial pacing percentage
      in conventional DDDR, non-optimal atrial pacing site, deleterious effects of high
      percentages of apical ventricular pacing. Atrial antitachycardia pacing (ATP)
      therapies are effective in treating spontaneous atrial tachyarrhythmias, mainly
      when delivered early after arrhythmia onset and/or on slower tachycardias.
      Effective ATP therapies may reduce atrial fibrillation burden, but conflicting
      evidence does exist as regards this issue, probably because current clinical
      studies may be underpowered to detect such an efficacy. Wide application of
      atrial ATP may reduce the need for hospitalizations and electrical cardioversions
      and favorably impact on quality of life. Consistent monitoring of atrial and
      ventricular rhythm as well as that of ATP effectiveness may be extremely useful
      for optimizing device programming and pharmacological therapy.

PMID- 15875510
TI  - The role of the implantable atrial cardioverter-defibrillator.
AB  - Atrial and dual-chamber defibrillators with atrial antitachycardia functions
      represent an emerging option for the treatment of patients with drug-refractory
      atrial fibrillation. Atrial cardioversion has been demonstrated to be highly
      effective in treating spontaneous tachyarrhythmias and may reduce atrial
      fibrillation burden by preventing atrial remodeling. Device implantation has been
      associated with an improved quality of life and a reduced hospitalization rate.
      Patient selection and tailored device programming are critical as regards
      clinical outcome. The individual psychological profile analysis as well as the
      underlying heart disease and clinical patterns of atrial fibrillation represent
      the main drivers for the right strategy. Controlled studies are needed in order
      to define the subset of patients who can benefit more from device implantation.

PMID- 15875511
TI  - Primary prevention of sudden cardiac death: indications for cardioverter
      defibrillator implantation.
AB  - Sudden cardiac death accounts for 400,000 to 450,000 deaths annually in Europe
      and in the United States. In patients with previous life-threatening arrhythmia,
      several perspective, randomized, controlled studies have demonstrated that
      implantable cardioverter-defibrillator (ICD) therapy is superior to the best
      antiarrhythmic therapy in prolonging survival. Furthermore, in a stratified-risk
      population with coronary artery disease, left ventricular ejection fraction < or
      = 35%, non-sustained ventricular arrhythmias, and inducible ventricular
      tachycardia, the ICD supports the class I level of recommendation by the
      guidelines published in 1998. The American College of Cardiology, American Heart
      Association, and North American Society of Pacing and Electrophysiology have
      updated the 1998 guidelines on the implantation of arrhythmia devices including
      in a class IIa level of recommendation also patients with a previous Q wave
      myocardial infarction and left ventricular ejection fraction < or = 30%,
      independently of their arrhythmic risk profile. In the recent years several
      randomized studies assessed the role of ICD treatment for primary prevention of
      sudden cardiac death and total mortality reduction in high-risk groups of
      patients with ischemic and non-ischemic dilated cardiomyopathy, with special
      reference to those with heart failure and ventricular dysfunction. This article
      reviews those trials that have resulted in defining indications for ICD, and that
      will expand its use in the future.

PMID- 15875512
TI  - Secondary prevention of sudden cardiac death.
AB  - Sudden cardiac death is still the largest cause of natural death in western
      countries, especially in patients with coronary artery disease and in those who
      have already experienced an episode of resuscitated out-of-hospital cardiac
      arrest or ventricular tachycardia. Prevention of arrhythmia recurrences (i.e.
      secondary prevention) in these patients remains a challenge for the cardiologist.
      To date no studies have demonstrated that drug therapy can be of some value in
      preventing arrhythmia recurrences or sudden death in these patients, and only
      cardioverter-defibrillator (ICD) implantation resulted effective in reducing
      mortality rate. It remains, however, to be defined which patients who survived an
      out-of-hospital cardiac arrest or who already experienced a sustained ventricular
      tachycardia could benefit the most from an ICD, but to date no invasive or non
      invasive tests have proven to be effective for this stratification. Vaughan
      Williams class II and III drugs could be of some value in reducing tachycardia
      cycle length thus increasing antitachycardia pacing efficacy and reducing ICD
      shocks.

PMID- 15875513
TI  - Ventricular tachycardia ablation.
AB  - The role of catheter ablation in the treatment of ventricular arrhythmias has
      been changing in the last decade, and this form of therapy now aims at curing
      multiple ventricular tachycardia morphologies and complex substrates in patients
      with structural heart disease (post-infarction and idiopathic dilated
      cardiomyopathy). Under these circumstances, conventional mapping is not feasible
      and accurate, and the development of new diagnostic methods has become necessary.
      The non-contact mapping system has been introduced to study the activation
      pattern of any ventricular arrhythmia by a "single-cycle" analysis, and has
      brought to the characterization of unstable and of non-sustained forms of
      arrhythmia. The evaluation of the arrhythmogenic substrate has similarly become
      more precise by the more common use of the electroanatomic mapping (CARTO), which
      is being applied to identify areas of scarred tissue responsible for ventricular
      arrhythmias, to map stable tachycardias and to validate the creation of a line of
      block. By means of this technological advancement, the identification of critical
      isthmi and deep intramural circuits has also led to new ablation strategies,
      frequently simplifying the procedure and minimizing complications.

PMID- 15875514
TI  - Surgical ablation of arrhythmias.
AB  - The surgical approach was the earliest therapeutic ablation of hyperkinetic
      arrhythmias. Following the progressive improvements in electrophysiological
      mapping and operative techniques, new surgical approaches have been developed for
      the treatment of those arrhythmias related to ectopic phenomena or reentry
      mechanisms. These procedures have been proven to be highly effective but the
      associated morbidity and mortality were unacceptably high. More recent and
      advanced techniques of transcatheter ablation have revolutionized the treatment
      of these arrhythmias and now represent the treatment of choice in the majority of
      cases. However, the significant reduction in the operative risk and the
      improvement in patient outcome with respect to the past, thanks to a better
      patient selection and to advances in the surgical and myocardial protection
      techniques, make do that the surgical approach to some forms of arrhythmias is
      still valid, especially in those cases requiring associated surgery: atrial
      tachyarrhythmias in patients with congenital heart disease, post-ischemic
      ventricular tachycardias in patients who necessitate myocardial
      revascularization, and/or ventricular remodeling and chronic or paroxysmal atrial
      fibrillation in patients who require cardiac surgery. New techniques such as
      radiofrequency, microwaves and cryoablation guarantee the creation of linear and
      transmural lesions with minimum damage to the cardiac structures and appear very
      interesting as they are surgically simple and associated with shorter procedure
      times and less complications. The possibility of performing the ablative
      procedure completely on the epicardial surface may open the way for atrial
      fibrillation surgery on a totally beating heart and for procedures that are ever
      less invasive thus enabling treatment of patients without associated surgical
      indications.

PMID- 15875515
TI  - Genetic arrhythmias.
AB  - The increasing interaction between molecular biology and clinical cardiology has
      allowed to demonstrate that mutations on the genes encoding cardiac ion channels
      or regulatory proteins can cause inherited arrhythmogenic disorders predisposing
      to sudden death in young individuals. These diseases are the long QT syndrome,
      the Brugada syndrome, the catecholaminergic polymorphic ventricular tachycardia,
      and the short QT syndrome. Since incomplete penetrance is present, genetic
      screening is pivotal to perform a correct diagnosis in mutation carriers who do
      not manifest phenotype, but are still at increased risk of cardiac events if left
      untreated. All these syndromes show genetic heterogeneity and it is becoming
      evident that each genetic variant of the disease presents distinguishing clinical
      characteristics suggesting that genetics may be used for targeting risk
      stratification and treatment of these diseases. In this chapter, the molecular
      bases, the clinical features and the current therapeutic approach of these
      syndromes are presented.

PMID- 15875516
TI  - Neurally-mediated syncope.
AB  - "Neurally-mediated (reflex) syncope" refers to a reflex response that, when
      triggered, gives rise to vasodilation and/or bradycardia; however, the
      contribution of each of these two factors to systemic hypotension and cerebral
      hypoperfusion may differ considerably. The initial evaluation may lead to a
      certain diagnosis in the case of classical vasovagal syncope and of situational
      syncope. Classical vasovagal syncope is diagnosed if precipitating events such as
      fear, severe pain, emotional distress, instrumentation or prolonged standing, are
      associated with typical prodromal symptoms. Situational syncope is diagnosed if
      syncope occurs during or immediately after urination, defecation, cough or
      swallowing. In the absence of a certain diagnosis, absence of cardiac disease,
      long history of syncope, syncope after sudden unexpected unpleasant sight, sound
      or smell, prolonged standing at attention or crowded, warm places, nausea and
      vomiting, post-prandial and post-exercise state suggest a neurally-mediated cause
      which needs to be confirmed by specific tests. Among them, the most useful are
      carotid sinus massage and tilt testing. In general, education and reassurance are
      the sufficient initial treatment. Additional treatment may be necessary in high
      risk or high-frequency settings. Treatment is not necessary in patients who have
      sustained a single syncope and are not having syncope in a high-risk setting. It
      is valuable to assess the relative contribution of cardioinhibition and
      vasodepression before embarking on treatment as there are different therapeutic
      strategies for the two aspects. Even if evidence of utility of such an assessment
      exists only for the carotid sinus massage, it is recommended to extend this
      assessment also by means of tilt testing or implantable loop recorder. Tilt
      training and isometric leg and arm counterpressure maneuvers are indicated in
      patients with recurrent vasovagal syncope. Cardiac pacing is indicated in
      patients with cardioinhibitory or mixed carotid sinus syndrome and in patients
      with cardioinhibitory vasovagal syncope with a frequency > 5 attacks per year or
      severe physical injury or accident and age > 40 years. The evidence fails to
      support the efficacy of any drug.

PMID- 15875517
TI  - Cardiac resynchronization therapy in heart failure.
AB  - Cardiac resynchronization therapy (CRT) is a new therapeutic approach for a
      selected group of patients with symptomatic heart failure (NYHA functional class
      III-IV) despite optimal medical therapy, due to dilated cardiomyopathy of any
      etiology (left ventricular ejection fraction < or = 35% and left ventricular end
      diastolic diameter > or = 55 mm), who present with electromechanical dyssynchrony
      (QRS > or = 130 ms). Safety and effectiveness of CRT have been demonstrated by
      several clinical trials, with patients achieving significant improvement in both
      clinical symptoms as well as functional status and exercise capacity.
      Furthermore, CRT has reduced morbidity of heart failure patients, while its
      impact in improving survival still remains to be clarified. Whether or not heart
      failure patients candidate to CRT should receive a defibrillator back-up remains
      debatable, although growing evidence is pointing to extensive use of a
      defibrillator in such a population.

PMID- 15875518
TI  - Pacing and implantable cardioverter-defibrillator transvenous lead extraction.
AB  - During the last 20 years, the transvenous techniques for the extraction of
      chronically implanted pacing (PL) and defibrillating leads (DL) achieved a high
      success rate. However the procedures are often complex and are associated with a
      small but significant risk. The operators' experience and the availability of
      different approaches for difficult cases seem to affect both the results and the
      complications. This paper represents a review of indications, techniques and
      results of a 10-year experience in the field of transvenous lead extraction.
      Since January 1997, extraction was attempted in 1330 leads; among these 1137 were
      successfully extracted with the standard mechanical approach (success rate
      85.4%); in 12 leads was performed a partial extraction (0.9%) and 1 was
      inapplicable (0.07%). The jugular approach was performed in 180 leads (164 PL and
      16 DL): 39 were intravascular free-floating leads (38 PL and 1 DL) and 141 were
      difficult exposed leads (126 PL and 15 DL) allowing extraction in 178/180 (98.8%)
      cases. After this approach, the final results were: total extraction 98.88%,
      partial extraction 0.90%, unextracted 0.15%, and not applicable 0.07%. Major
      complications occurred in 4 cases (0.3%) and were cardiac tamponade (2 underwent
      successful pericardiocentesis, 1 surgical repair, and 1 patient died). No
      complications were directly related to the jugular approach. In conclusion,
      transvenous lead extraction is an effective and safe procedure. The success rate
      and the incidence of complications are highly affected by the staff experience.
      The use of the jugular approach, in the presence of free-floating or difficult
      exposed leads, increases both safety and success rate.

PMID- 15875519
TI  - Stem cell therapy for cardiac arrhythmias.
AB  - Clinical studies suggest that stem cell transplantation (SCT) is feasible and has
      the potential for beneficial effects in several cardiac affections, including
      myocardial infarction and advanced heart failure. However, concern exists about
      the possible occurrence of serious arrhythmias after SCT, even if such
      complication has been shown only in case of skeletal myoblast transplantation.
      SCT might induce arrhythmias by several mechanisms, such as electrotonic
      stimulation of cardiac cells, electrical heterogeneity of action potentials
      during stem cell differentiation process, increased nerve sprouting, and local
      tissue injury induced by intramyocardial injection. As a matter of fact, the use
      of endothelial progenitor cells from the peripheral blood or of stem cells from
      bone marrow has not been associated with any significant cardiac rhythm
      disturbance. Recently, a new opportunity for SCT has emerged: the development of
      a biological cardiac pacemaker. Both gene therapy and cell therapy have been used
      in this new perspective. In fact, at present, the transformation of a normal
      cardiomyocyte in a pacemaker cell can be obtained in animal models by the
      injection of a plasmid or virus, incorporating the gene encoding for specific
      proteins. This procedure transforms cardiomyocytes in transgenic cells that may
      show an overexpression of beta2-adrenergic receptors, or abnormal membrane ion
      channels. As an alternative, genetically modified mesenchymal stem cells can be
      delivered within the heart and engraft to develop a biological pacemaker. To
      date, several studies have been performed in different animal models employing
      both cell and gene therapy. However, complex problems concerning safety and
      efficacy require a solution before we can move to the step of clinical evaluation
      in human beings.

PMID- 15875520
TI  - The Italian Implantable Cardioverter-Defibrillator Registry. A survey of the
      national activity during the years 2001-2003.
AB  - BACKGROUND: In recent years several trials demonstrated the efficacy of
      implantable cardioverter-defibrillator (ICD) therapy for sudden cardiac death
      prevention and total mortality reduction in particular high-risk groups of
      patients. The aim of this review was to report the main epidemiological data and
      the most important clinical characteristics of patients enrolled in the Italian
      ICD Registry in the years 2001-2003. METHODS: The Italian ICD Registry--official
      member of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC)-
      collects 85% of the data concerning the national ICD implantation activity, based
      on the European Implantable Defibrillator form (EURID). Data are validated for
      quality of information and uniqueness at the moment of data entry and in
      successive steps at the time of the annual analysis. RESULTS: The number of ICDs
      implanted in Italy has been continuing to increase during the last years
      according to the general trend in European and non-European countries: 2400 in
      the year 2001, 3934 in the year 2002, and 5318 in the year 2003. The number of
      ICDs per million of inhabitants in Italy was 42.1 in the year 2001 (+11.8% with
      respect to 2000), 69.0 in the year 2002 (+63.9% with respect to 2001), and 93.3
      in the year 2003 (+35.2% with respect to 2002). The number of implanting centers
      increased progressively from 273 in the year 2001 to 304 in the year 2002, and
      340 in the year 2003. The median age of patients treated with ICD implantation
      was 67 years in the years 2001-2002, 68 years in the year 2003. The prevalence of
      male patients was significantly higher (79.3% in 2001, 82.3% in 2002, and 81.4%
      in 2003). The main indication was syncope (25.5, 29.3, and 32.9% in the years
      2001, 2002, and 2003, respectively), followed by palpitations (17.7, 18.5, and
      16.4% in the years 2001, 2002, and 2003, respectively), and cardiac arrest (10.0,
      13.1, and 16.5% in the years 2001, 2002, and 2003, respectively). The use of ICD
      in patients considered at risk but without history of sustained ventricular
      tachycardia had a 3-fold increase during the 3 years, from 6.4% in 2001 to 18.2%
      in 2003. Ventricular tachycardia was the main arrhythmia in 50.4 to 55.0% of
      cases, ventricular fibrillation in 13.5 to 18.1%, both in 4.1 to 6.5%. The vast
      majority of patients presented at the enrolment either a mild or severe reduction
      in ejection fraction (30 to 50%, < 30%). Amiodarone was administered alone or in
      combination with antiarrhythmics in 29.7 to 40.0% of patients. Single-chamber
      ICDs were implanted in the years 2002 and 2003 in 45.7 and 39.2% of patients,
      dual-chamber ICDs in 34.9 and 32.4%, biventricular ICDs in 19.4 and 28.4%,
      respectively. CONCLUSIONS: The ICD implantation rate in Italy increased
      significantly in the period 2001-2003, similarly to the trend in the other
      western countries and following the publication of controlled studies in the
      field of primary and secondary prevention of sudden cardiac death. The Italian
      ICD Registry showed during the last 3 years an important increase in prophylactic
      ICD utilization. A sophisticated ICD, including dual-chamber pacing or cardiac
      resynchronization therapy, was chosen in a high percentage of patients.

PMID- 15875521
TI  - Oaks.

PMID- 15875522
TI  - Improving asthma control: talk is not cheap.

PMID- 15875523
TI  - Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of the
      literature.
AB  - OBJECTIVE: To perform a comprehensive review of Stevens-Johnson syndrome and
      toxic epidermal necrolysis. DATA SOURCES: A MEDLINE search was performed for the
      years 1975 to 2003 using the keywords Stevens-Johnson syndrome and toxic
      epidermal necrolysis to identify relevant articles published in English in peer
      reviewed journals. STUDY SELECTION: All clinical studies that reported on 4 or
      more patients, review articles, and experimental studies that concerned disease
      mechanisms were selected and further analyzed. Clinical reports that included
      fewer than 4 patients were selected only if they were believed to carry a
      significant message about disease mechanism or therapy. RESULTS: Stevens-Johnson
      syndrome and toxic epidermal necrolysis seem to be variants of the same disease
      with differing severities. A widely accepted consensus regarding diagnostic
      criteria and therapy does not exist at present. Despite the recent experimental
      studies, the pathogenic mechanisms of these diseases remain unknown. Although
      progress in survival through early hospitalization in specialized burn units has
      been made, the prevalence of life-long disability from the ocular morbidity of
      Stevens-Johnson syndrome and toxic epidermal necrolysis has remained unchanged
      for the past 35 years. Further progress depends on modification of the acute
      phase of the disease rather than continuation of supportive care. The available
      published evidence indicates that a principal problem in the pathogenesis is
      immunologic and that immunomodulatory intervention with short-term, high-dose
      intravenous steroids or intravenous immunoglobulin holds the most promise for
      effective change in survival and long-term morbidity. CONCLUSIONS: The results of
      this review call for a widely accepted consensus on diagnostic criteria for
      Stevens-Johnson and toxic epidermal necrolysis and multicenter collaboration in
      experimental studies and clinical trials that investigate disease mechanisms and
      novel therapeutic interventions, respectively.

PMID- 15875524
TI  - Cough, wheezing, and rash in a patient with a history of allergic
      bronchopulmonary aspergillosis.

PMID- 15875525
TI  - Declining cell-mediated immunity and increased chronic disease burden.
AB  - BACKGROUND: The effects of chronic disease have been proposed as an explanation
      for conflicting results in studies of age effects on cell-mediated immunity.
      OBJECTIVE: To examine the hypothesis that declining cell-mediated immunity is
      more closely linked to chronic disease burden than to chronological age. METHODS:
      Fifty-eight elderly individuals were tested for delayed-type hypersensitivity
      (DTH) responses to Candida and tetanus antigens. Disease burden was quantified
      using the Cumulative Illness Rating Scale (CIRS). Higher CIRS scores reflect
      greater disease burden. Mean DTH response by age group (<71, 71-78, and >78
      years) was compared with mean DTH response by CIRS score (<11, 11-15, >15). Total
      serum IgE levels were measured and similarly stratified by age and CIRS score.
      RESULTS: Mean Candida DTH responsiveness declined progressively with increasing
      disease burden (increasing CIRS score). Mean DTH responses were 7.78, 3.05, and
      0.0 mm for CIRS scores less than 11, 11 to 15, and greater than 15, respectively.
      Candida DTH responses showed no progressive decline with advancing age. Mean DTH
      responses were 4.7, 3.5, and 5.0 mm in participants younger than 71, 71 to 78,
      and older than 78 years, respectively. Total serum IgE levels increased with
      advancing age. Mean total IgE levels were 182, 249, and 342 IU/mL in participants
      younger than 71, 71 to 78, and older than 78 years, respectively. No correlation
      was observed between mean total IgE levels and CIRS scores. CONCLUSIONS: An
      inverse relationship between Candida DTH response and CIRS score suggests that
      increased chronic disease burden is associated with diminished cell-mediated
      immune response. Advancing age did not predict a diminished DTH response in our
      patients. No relationship was observed between chronic disease burden and total
      serum IgE level.

PMID- 15875526
TI  - Comparison of 2 maintenance doses (100 microg vs 200 microg) in Hymenoptera venom
      immunotherapy: influence of the maintenance dose on the immunologic response.
AB  - BACKGROUND: In Hymenoptera venom immunotherapy, the maintenance dose is usually
      100 microg. However, persistent systemic reactions to sting challenges could be
      treated by an increase in the maintenance dose to 200 microg with success,
      suggesting greater efficiency. OBJECTIVE: To compare the effects of 2 monthly
      maintenance doses (100 microg vs 200 microg) on skin test sensitivity and venom
      specific IgE antibody levels. METHODS: Twenty-two patients receiving Vespula
      venom immunotherapy were enrolled in this retrospective study. After rush
      therapy, the 100-microg maintenance dose initially administered was maintained
      (group 1, n = 13) or was increased to 200 microg (group 2, n = 9). RESULTS:
      Levels of venom specific IgE antibody and skin test results measured before the
      onset of immunotherapy were comparable in both groups. Unlike in group 1, a
      maintenance dose of 200 microg resulted in significant decreases in venom
      specific IgE antibody levels and skin test sensitivity. CONCLUSIONS: Increasing
      the monthly maintenance dose to 200 microg results in a greater degree of change
      in venom specific IgE antibody levels and skin test sensitivity than when
      maintaining a 100-microg dose. Our data strengthen those of previous clinical
      studies showing the usefulness of a 200-microg maintenance dose in the case of
      clinical failure of a 100-microg dose.

PMID- 15875527
TI  - The efficacy of short-term administration of 3 antihistamines vs placebo under
      natural exposure to Japanese cedar pollen.
AB  - BACKGROUND: Japanese cedar pollinosis, a common disease with morbidity of
      approximately 20% in the Japanese population, is characterized by subjectively
      irritating symptoms during an annual 3-month period. OBJECTIVE: To investigate
      the effectiveness of cetirizine hydrochloride, loratadine, and fexofenadine
      hydrochloride in reducing pollinosis symptoms induced while walking in a park
      during the pollen season. METHODS: A randomized, double-masked, placebo
      controlled trial was conducted in 113 individuals with Japanese cedar pollinosis
      during 2 days in March 2003 in Osaka Expo Park, Osaka, Japan. Participants (aged
      20-57 years) were divided into 4 groups according to treatment assignment:
      cetirizine hydrochloride, 10 mg/d; fexofenadine hydrochloride, 120 mg/d;
      loratadine, 10 mg/d; and placebo (lactose), twice daily. Symptoms were recorded
      hourly during the study. Furthermore, all the patients completed the Japanese
      version of the Rhinoconjunctivitis Quality of Life Questionnaire before and after
      the trial. RESULTS: Self-evaluated symptom scores in all 3 active treatment
      groups showed significant improvements compared with the placebo group.
      Furthermore, the cetirizine group showed significant improvement in the domains
      of frequency of nose blowing and nasal obstruction compared with placebo. In
      addition, improvement in Japanese Rhinoconjunctivitis Quality of Life
      Questionnaire scores was higher in the cetirizine group than in the loratadine
      and placebo groups. CONCLUSION: Cetirizine seems to be more effective than
      fexofenadine and loratadine at reducing subjective symptoms in this study
      population.

PMID- 15875528
TI  - Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis
      function in adults with mild-to-moderate persistent asthma.
AB  - BACKGROUND: Despite their proven efficacy in the treatment and prevention of
      asthma exacerbations, current inhaled corticosteroids carry safety concerns,
      especially adrenal suppression. Ciclesonide (hydrofluoroalkane propellant) is a
      novel inhaled corticosteroid with few, if any, clinical adverse events.
      OBJECTIVE: To evaluate the potential effects of ciclesonide therapy on the
      dynamic cortisol response to sequential low- and high-dose cosyntropin
      stimulation in adults with mild-to-moderate persistent asthma. METHODS: This was
      a double-blind, randomized, placebo-controlled, 12-week study in adults with mild
      to-moderate asthma. One hundred sixty-four patients were randomized and treated;
      148 patients completed the study. Fluticasone propionate (chlorofluorocarbon
      propellant) was used as an active comparator. The doses administered were 320
      microg of ciclesonide once daily, 320 microg of ciclesonide twice daily, and 440
      microg of fluticasone propionate twice daily, all doses ex-actuator. RESULTS: For
      both ciclesonide groups, changes in mean low- and high-dose peak serum cortisol
      levels and in 24-hour urinary free cortisol levels corrected for creatinine were
      small vs baseline and comparable with placebo. For the fluticasone propionate
      group, significant reductions vs placebo in serum cortisol levels in response to
      high-dose cosyntropin stimulation and in 24-hour urinary free cortisol levels
      were observed. Oral candidiasis rates were 2.5% for 320-microg/d ciclesonide,
      2.4% for 640-microg/d ciclesonide, and 22.0% for 880-microg/d fluticasone
      propionate. CONCLUSIONS: These findings confirm the safety of ciclesonide
      therapy, demonstrating that at doses up to 640 microg/d, the drug does not affect
      sensitive markers of adrenal function.

PMID- 15875529
TI  - Correlates of quality of life in patients with asthma.
AB  - BACKGROUND: Health-related quality of life (HRQOL) is a major outcome in asthma,
      but the relationships among HRQOL, characteristics of asthma, type of
      supervision, and sociodemographic characteristics of patients have not been
      thoroughly explored. OBJECTIVE: To identify major correlates of HRQOL in a survey
      of patients with asthma. METHODS: Patients with asthma were identified by their
      usual caregivers, either general practitioners or respiratory physicians. In a
      standardized interview, data were collected on patients' sociodemographic
      characteristics, medical history, medical resource use in the past 12 months, and
      asthma QOL. Intensity of asthma therapy was evaluated from the use of inhaled
      controllers and oral corticosteroids in the past 12 months, and number of asthma
      attacks during the same period was used as an indicator of level of asthma
      symptoms. RESULTS: Ninety-nine patients with asthma were identified (median age,
      36 years; 62.6% women). In multivariate analysis, major correlates for lower
      HRQOL scores were having at least 5 asthma attacks and the number of medical
      visits in the past 12 months (P < .001 for both). Other significant positive
      associations were unemployment (P = .01) and female sex (P = .05), but not
      intensity of therapy, age, or type of asthma supervision (general practitioner vs
      respiratory physician). CONCLUSIONS: In this survey, HRQOL scores seem to be
      primarily related to asthma symptoms, as indicated by the number of attacks
      experienced by the patients and the frequency of medical contacts in a previous
      period. The relationships among HRQOL, therapy, and the determinants of control
      should be investigated in prospective studies.

PMID- 15875530
TI  - Effect of lycopene supplementation on lung function after exercise in young
      athletes who complain of exercise-induced bronchoconstriction symptoms.
AB  - BACKGROUND: It has been suggested that exercise-induced bronchoconstriction may
      involve oxidative stress. Strenuous exercise promotes free radical production,
      which can lead to many of the pathophysiologic changes associated with asthma,
      including bronchoconstriction, mucus secretion, and microvascular leakage.
      Lycopene has been shown to have high antioxidative activity. OBJECTIVE: To
      evaluate the effect of lycopene supplementation on airway hyperreactivity and
      inflammation in young athletes who complain of difficulty in breathing related to
      physical exertion. METHODS: Nineteen young athletes with exercise-related
      difficulty in breathing visited the exercise laboratory 3 times. During the first
      visit, participants underwent a baseline evaluation of exercise-induced
      bronchoconstriction. Daily for 1 week before each of the 2 subsequent visits,
      participants ingested 30 mg of lycopene (a natural antioxidant) or placebo (in
      randomized order, double-blind). A 2-week washout period was given between each
      visit. During each visit, lung functions were evaluated before and after an 8
      minute run on the treadmill (85% of the predicted maximal heart rate). RESULTS:
      There was no difference in the mean+/-SD decrease in forced expiratory volume in
      1 second after exercise during lycopene treatment compared with placebo treatment
      (11.8%+/-12.5% and 11.0%+/-11.6%). In addition, there was no apparent division
      into responders and nonresponders. CONCLUSION: A daily dose of lycopene for 1
      week does not affect lung function after exercise and may not provide any
      protective effect against clinical difficulty in breathing in young athletes.

PMID- 15875531
TI  - Toll-like receptor 2 expression on human conjunctival epithelial cells: a pathway
      for Staphylococcus aureus involvement in chronic ocular proinflammatory
      responses.
AB  - BACKGROUND: Staphylococcus aureus colonization is common in atopic
      keratoconjunctivitis, potentially activating epithelial cells via toll-like
      receptor 2 (TLR-2) and the receptor for platelet-activating factor (PAFR).
      OBJECTIVES: To examine human conjunctival epithelial cells for the expression of
      TLR-2 in vitro and in vivo and to evaluate the role of TLR-2 in S aureus-mediated
      activation of these cells. METHODS: Conjunctival epithelial cells isolated from
      cadaveric tissues were stimulated with interferon gamma (IFN-gamma) or a
      commercial S aureus cell wall extract (Staphylococcus aureus-CWE) (with or
      without anti-TLR-2 blocking antibody or PAFR antagonist) and were analyzed for
      tumor necrosis factor alpha (TNF-alpha) and interleukin 8 (IL-8) release; surface
      expression of TLR-2, intercellular adhesion molecule-1, HLA, and CD14; and TLR-2
      messenger RNA expression. Ocular surface cells collected via impression cytology
      were examined for TLR-2 expression via flow cytometry. RESULTS: Expression of TLR
      2 was up-regulated on conjunctival epithelial cells by IFN-gamma and
      Staphylococcus aureus-CWE. Expression of TLR-2 messenger RNA was increased by IFN
      gamma. Staphylococcus aureus-CWE up-regulated intercellular adhesion molecule 1,
      HLA, and CD14 expression and increased TNF-alpha and IL-8 release in a dose
      dependent manner. Anti-TLR-2 significantly inhibited TNF-alpha release, whereas
      PAFR antagonist significantly inhibited IL-8 release. Toll-like receptor 2 was
      expressed on conjunctival epithelial cells from 4 of 5 patients with atopic
      keratoconjunctivitis, 3 of 5 with seasonal allergies, and 0 of 3 without
      allergies. CONCLUSIONS: Conjunctival epithelial cells express TLR-2 and may play
      an active role in the chronic ocular inflammatory response to S aureus through
      pathways that involve TLR-2 and PAFR.

PMID- 15875532
TI  - Hereditary angioedema due to C1 inhibitor deficiency: patient registry and
      approach to the prevalence in Spain.
AB  - BACKGROUND: Hereditary angioedema (HAE) is a rare disease caused by C1 inhibitor
      mutations. Although more than 100 mutations have been described, epidemiologic
      data are lacking; therefore, we developed a Spanish HAE patient registry.
      OBJECTIVE: To study the prevalence of HAE and the current state of diagnosis and
      treatment of this disease in Spain. METHODS: Epidemiologic data were obtained by
      direct contact with physicians who treat patients with HAE and with patients
      themselves. Diagnosis was evaluated by measuring C1 inhibitor levels and
      function, and most families also underwent genetic studies. RESULTS: We
      registered 444 patients (minimal prevalence, 1.09 per 100,000 inhabitants), many
      of whom are asymptomatic (never having symptoms) (n = 61, 13.7%). Most
      symptomatic patients (62.9%) receive long-term prophylaxis with attenuated
      androgens (80.9%) and antifibrinolytic agents (22.8%), alone or in combination,
      but no patients are receiving long-term prophylaxis with C1 inhibitor. There is a
      long delay in diagnosis (mean, 13.1 years). Nine patients underwent a tracheotomy
      as a consequence of a laryngeal attack, and 30 families recalled a total of 38
      relatives who died of HAE, which underlines the severity of the illness.
      CONCLUSIONS: The detected minimal prevalence of HAE in Spain is 1.09 per 100,000
      inhabitants. Because this is a rare disease and some patients may be
      misdiagnosed, this prevalence could be higher.

PMID- 15875533
TI  - Chlamydia pneumoniae arthritis in a patient with common variable
      immunodeficiency.
AB  - BACKGROUND: Arthritis is an important and sometimes life-threatening complication
      in patients with common variable immunodeficiency (CVID). OBJECTIVE: To describe
      a patient with CVID and arthritis due to Chlamydia pneumoniae, which is usually
      regarded as a respiratory tract pathogen and has not previously been detected in
      the synovial fluid by cell culture technique. METHODS: Routine bacteriologic,
      virologic, mycologic, and tuberculosis cultures were performed. The patient's
      synovial fluid was examined for fastidious organisms that might be causative
      pathogens of arthritis, such as chlamydiae, and special cell culture methods were
      used. Serologic tests were performed to determine viral and bacteriologic
      etiology. RESULTS: The patient had a history of recurrent respiratory tract
      infections, and the latest exacerbation was followed by arthritis. Cytologic
      examination of the fluid yielded abundant lymphocytes. Chlamydia pneumoniae was
      detected in synovial fluid specimens by cell culture technique. Her
      nasopharyngeal swab and sputum culture specimens were also positive for this
      pathogen. She was diagnosed as having arthritis caused by C pneumoniae and was
      given antibiotherapy. CONCLUSION: Chlamydia pneumoniae should be kept in mind as
      a causative pathogen in patients with CVID and arthritis, especially when
      effusion fluid is full of lymphocytes rather than polymorphonuclear cells and no
      organism is grown on routine cultures.

PMID- 15875534
TI  - Psoriasiform contact dermatitis due to propolis in a beekeeper.
AB  - BACKGROUND: More than 250 cases of allergic contact dermatitis due to propolis
      have been described. A few of these occurred in beekeepers. OBJECTIVE: To
      describe a case of psoriasiform dermatitis caused by propolis in a beekeeper who
      thought that his lesions were related to honeybee stings. METHODS: A 45-year-old
      beekeeper experienced hand dermatitis for the past 5 years. He believed that the
      lesions occurred and worsened when he was stung by honeybees. He was prescribed
      topical corticosteroids several times, but because he was stung frequently, the
      drugs never helped control the lesions. In the past few years, he frequently had
      contact with propolis during honey collection, but he denied the role of propolis
      because he was wearing gloves while handling the beehives. For diagnostic
      evaluation, skin biopsy, skin prick tests (SPTs), identification of specific IgE
      antibodies, and atopic patch tests were performed. RESULTS: Skin biopsy showed
      psoriasiform contact dermatitis. Results of SPTs to honeybee and serum specific
      IgE for Apis mellifera remained negative. Results of the atopic patch test
      performed using A mellifera SPT material were also negative in the first 20
      minutes and on the second and third days. However, propolis showed a positive
      erythematopapular reaction on day 2. The patient never again worked as a
      beekeeper, and neither did he, as far as he knew, use any medical or cosmetic
      products that contained propolis. His hand lesions improved almost completely.
      CONCLUSION: Dermatitis due to propolis should never be disregarded in beekeepers,
      and every effort should be put forth to make a correct diagnosis and to convince
      the patients of the cause.

PMID- 15875535
TI  - Thiazolidinedione treatment attenuates diffuse neointimal hyperplasia in
      restenotic lesions after coronary stent implantation in type 2 diabetic patients:
      an intravascular ultrasound study.
AB  - OBJECTIVES: Thiazolidinedione treatment reduces neointimal tissue proliferation
      after coronary stent implantation in diabetic patients. However, in-stent
      restenosis still persists in patients treated with thiazolidinedione. The effect
      of thiazolidinedione treatment on the pattern of in-stent restenosis remains
      unclear. This study investigated whether thiazolidinedione treatment attenuates
      diffuse neointimal hyperplasia in restenotic lesions after coronary stent
      implantation in diabetic patients. METHODS: Volumetric intravascular ultrasound
      was performed at 6 months after coronary stent implantation in 76 patients with
      restenotic lesions who received either conventional anti-diabetic treatment
      (control group, n = 56) or thiazolidinedione treatment (thiazolidinedione group,
      n = 20). RESULTS: There were no significant differences between the two groups in
      stent volume (99 +/- 32 vs 90 +/- 20 mm3, respectively, p = 0.26) or in minimal
      lumen area in the stent (1.4 +/- 0.6 vs 1.6 +/- 0.5 mm2, respectively, p = 0.11).
      However, there were significant reductions in neointimal volume (56 +/- 25 vs 36
      +/- 11 mm3, respectively, p < 0.01)and neointimal index (56 +/- 11% vs 41 +/- 8%,
      respectively, p < 0.01) in the thiazolidinedione group. Coefficient of variation
      of neointimal tissue accumulation was greater in the thiazolidinedione group
      (45.5%) than in the control group (25.2%). CONCLUSIONS: Intravascular ultrasound
      study demonstrated that together with reduction of overall neointimal tissue
      proliferation, thiazolidinedione treatment caused greater point-to-point
      heterogeneity in the neointimal tissue accumulation in restenotic lesions after
      coronary stent implantation. This finding strongly suggests that
      thiazolidinedione treatment attenuates diffuse in-stent restenosis in diabetic
      patients.

PMID- 15875536
TI  - [Predictors of hemodynamically successful left pulmonary artery stent
      implantation in patients after repair of tetralogy of Fallot].
AB  - OBJECTIVES: Left pulmonary artery stenosis is a well-known postoperative
      complication in patients with tetralogy of Fallot. Recently, balloon expandable
      intravascular stents have been widely used to relieve those lesions. However, the
      increase in left pulmonary blood flow is not adequate in some patients, although
      the vessels are suitably dilated. This study evaluated the predictors of
      hemodynamical improvement. METHODS: The study population consisted of nine
      patients with morphologically successful stent implantation for left pulmonary
      artery stenosis after repair of tetralogy of Fallot. Patients were divided into
      two groups. Four patients had hemodynamical improvement by stent implantation,
      with relative perfusion of the left lung of over 30% of total pulmonary
      perfusion. The other five patients had relative perfusion of the left lung of
      under 30% of total pulmonary perfusion after stent implantation. The timing of
      stent implantation and the morphological features of pulmonary artery were
      compared between the two groups. RESULTS: In hemodynamically improved patients,
      the stent implantation was performed earlier(6.1 +/- 3.5 vs 16.1 +/- 6.5 years
      old, p = 0.029), and the interval between surgical repair and stenting was
      shorter (3.7 +/- 2.7 vs 11.3 +/- 4.7 years, p = 0.025). There was no difference
      in the left pulmonary artery diameter after stenting, but the right pulmonary
      artery diameter was significantly smaller in hemodynamically improved patients
      (99.0 +/- 23.7 vs 135.0 +/- 15.1% normal, p = 0.027). CONCLUSIONS: Effective
      stent implantation for left pulmonary artery stenosis in patients with tetralogy
      of Fallot after repair must be performed before compensatory right pulmonary
      artery growth occurs.

PMID- 15875537
TI  - Hypertrophic cardiomyopathy with progression from apical hypertrophy to
      asymmetrical septal hypertrophy: a case report.
AB  - A 41-year-old man was referred to our hospital for further examination because of
      abnormal electrocardiography findings at a health-check examination.
      Transthoracic echocardiography showed left ventricular hypertrophy confined to
      the most distal portion of the left ventricle, which is a typical feature of
      apical hypertrophic cardiomyopathy. Ten years later, he was again admitted for
      the evaluation of chest pain. Echocardiography showed asymmetrical septal
      hypertrophy in addition to apical hypertrophy. These findings demonstrate
      morphologic evolution in hypertrophic cardiomyopathy from apical hypertrophy to
      asymmetrical septal hypertrophy.

PMID- 15875538
TI  - Esophageal varices without portosystemic venous pressure gradient in a patient
      with post-pericardiotomy constrictive pericarditis: a case report.
AB  - A 51-year-old woman was admitted with intractable congestive heart failure and
      progressive anemia. She had undergone mitral valve replacement for mitral
      regurgitation at age 23 years. Subsequently, her mitral prosthesis was replaced
      twice due to thrombotic stack and valve insufficiency. Signs of congestive heart
      failure became evident at age 46 years. Gastrointestinal endoscopy revealed
      esophageal varices, which were treated by endoscopic variceal ligation. Cardiac
      catheterization disclosed elevated pulmonary capillary wedge pressure (mean 16
      mmHg), right atrial pressure (mean 15 mmHg), and hepatic vein wedge pressure
      (mean 15 mmHg). She died at age 53 years. Autopsy showed severe congestive liver
      but not liver cirrhosis. Esophageal varices may progress in spite of the absence
      of porto-systemic pressure gradient in patients with severely high venous
      pressure.

PMID- 15875539
TI  - [Long-surviving patient with isolated absent pulmonary valve syndrome: a case
      report].
AB  - A 79-year-old woman was admitted for exertional dyspnea in September 2001. She
      had begun to experience unusual fatigue from the age of 40 years. Cardiac
      examination revealed a single S2, Levine grade II/VI presystolic murmur in the
      5th left sternal border, and a right parasternal impulse. Echocardiography showed
      dilated right chambers and absence of pulmonary valve leaflets. Doppler
      echocardiography at the pulmonary annulus revealed a 'to and fro' pattern.
      Cardiac catheterization indicated the same diastolic pressures in the pulmonary
      artery and right ventricle. The diagnosis was absent pulmonary valve syndrome.
      Administration of a diuretic agent resulted in almost immediate improvement of
      symptoms. Absent pulmonary valve syndrome, generally associated with tetralogy of
      Fallot, often causes severe respiratory failure or right heart failure during
      infancy. A case of such long survival without associated cardiac anomalies is
      very rare.

PMID- 15875540
TI  - [Fluorodeoxyglucose-positron emission tomographic findings in a patient with
      pacing failure].

PMID- 15875541
TI  - Chiari network: do all cardiologists know of its existence?

PMID- 15875542
TI  - [Autophagy: a strategy for neogenesis].

PMID- 15875543
TI  - [Inhibition of axon regeneration by myelin inhibitors].

PMID- 15875545
TI  - [X-ray crystallography of a nuclear export complex].

PMID- 15875544
TI  - [Stem cell regulation in plants].

PMID- 15875546
TI  - [Discovery of chignolin, a " protein" consisting of only ten amino acids].

PMID- 15875547
TI  - [Novel function of sodium pump].

PMID- 15875548
TI  - [D-amino acid biosystem in mammals].

PMID- 15875549
TI  - [Peptide ribonucleic acids (PRNA): novel strategy for active control of DNA
      recognition by external factors].

PMID- 15875550
TI  - Important contributions to cardiothoracic surgery by Japanese thoracic and
      cardiac surgeons.
AB  - Cardiothoracic surgeons in Japan have made outstanding contributions to our
      knowledge and therapy of diseases and anomalies of the heart, lungs, esophagus,
      chest wall and diaphragm. It is an honor for me to address this subject at the
      57th Annual Meeting of the Japanese Association for Thoracic Surgery in Sapporo
      because your President, Tomio Abe, is a valued friend and colleague who worked
      with me and my group as a Research Fellow at Washington U. from 1970-1973. He was
      recommended by Prof. Juro Wada, then the Chief in Sapporo. I was privileged to
      meet Prof. Wada at U.S. meetings. One of Prof. Wada's many contributions was the
      first cardiac transplant in Japan. Dr. Abe's work in St. Louis led to 12
      publications and he was the first author of two papers. Since, his contributions
      expanded to more than 550 publications on treatment of complex congenital heart
      diseases, ventricular assistance, myocardial protection, valvular heart disease
      and aortic aneurysms. An operation for correction of Taussig-Bing malformation
      reported in 1984 is now referred to as the Abe operation. Torikata, in 1925,
      introduced "free thoracotomy" with no differential pressure. In 1933, Ohsawa
      successfully resected the esophagus with immediate reconstruction-the first in
      the world. Wada, in 1963, developed a thermodisc oxygenator and in 1966 the first
      tilting disc heart valve-the Wada Cutter Valve and other contributions as a
      worldwide ambassador for Japanese Surgery. Kawata, et al. showed better
      ventricular function after patch reconstruction of left ventricular aneurysms.
      Ueda, et al. revived retrograde cerebral perfusion for repair of aortic arch
      aneurysms. Nakayama, Akiyama and Isono made important contributions to esophageal
      cancer surgery. Kimoto, et al., in 1956, performed open cardiac surgery under
      direct vision with brain cooling by irrigation. Sakakibara, et al., Hikasa, et
      al., Atsumi, et al., and Takano and Akutsu made contributions to cardiac surgery.
      There were many other contributions by Japanese Surgeons.

PMID- 15875551
TI  - Early results of off-pump coronary artery bypass grafting for patients on chronic
      renal dialysis.
AB  - OBJECTIVE: Renal dialysis is one of the independent risk factors for coronary
      artery bypass graft surgery. Off-pump coronary artery bypass grafting (OPCAB) may
      become a good option for these patients. In this study, early results as well as
      surgical techniques of OPCAB in dialysis patients were analyzed compared with non
      dialysis patients. METHODS: Between July 1997 and December 2002, 471 consecutive
      patients who underwent OPCAB were enrolled in this study. Among them, 20 patients
      (4.2%) had received hemodialysis regularly for more than 3 months until the
      operation. Severity of coronary artery disease or clinical presentations had no
      significant difference, however, left ventricular function was significantly
      impaired in dialysis patients. RESULTS: The average number of anastomosis was 2.8
      +/- 1.0 in the dialysis group and 3.2 +/- 1.0 in the non-dialysis group
      (p=0.056). Twelve patients (60.0%) received 3 or more bypass grafts in the
      dialysis group. Among them, 6 patients were revascularized only by in-situ or
      composite arterial conduits using bilateral internal thoracic arteries with or
      without the gastroepiploic artery. No patients required aortic clamping in the
      dialysis group. There was no mortality or morbidity in dialysis patients.
      Perioperaitve bleeding and mechanical ventilation time in the intensive care unit
      was similar in both groups. No dialysis patients required prolonged mechanical
      ventilation and hemodialysis from the beginning of the operation to extubation.
      CONCLUSION: The rationale for OPCAB for dialysis patients has been established.
      Total arterial revascularization without aortic clamping is applicable for
      dialysis patients who require multivessel bypass grafts.

PMID- 15875552
TI  - Pericardial metastasis of myxoid liposarcoma causing cardiac tamponade.
AB  - Although myxoid liposarcoma often metastasizes to various organs, cardiac
      metastasis is rare. We present herein a rare case with pericardial metastasis of
      myxoid liposarcoma, which expanded the pericardial sac extraordinarily and
      required an emergency operation because of acute cardiac tamponade. We undertook
      a review of the English literature regarding liposarcoma.

PMID- 15875553
TI  - False positive accumulation in 18F fluorodeoxyglucose positron emission
      tomography scan due to sarcoid reaction following induction chemotherapy for lung
      cancer.
AB  - We present a case of lung cancer that showed false positive accumulation in an
      18F fluorodeoxyglucose positron emission tomography (FDG-PET) scan following
      induction chemotherapy for suspected metastasis and progression of malignancy. A
      66-year-old man was diagnosed with squamous cell carcinoma in the lung,
      classified as clinical stage IIIA (T2N2M0), and underwent induction chemotherapy.
      An FDG-PET scan prior to chemotherapy demonstrated accumulation only in the
      tumor, whereas following treatment it revealed a strong accumulation not only in
      the tumor, but also in the supraclavicular lymph nodes, which indicated lymph
      node metastasis. The patient underwent a biopsy of the right supraclavicular
      lymph node and mediastinoscopy, after which all dissected lymph nodes showed
      sarcoid reactions and no tumor cells were found pathologically. We concluded that
      when evaluating the effect of induction chemotherapy for malignancy, a sarcoid
      reaction might lead to the false positive accumulation of FDG.

PMID- 15875554
TI  - Emergent permanent pacemaker implantation in a premature 1,502 g neonate.
AB  - We report a case of an emergent pacemaker implantation in a 1,502 g preterm
      neonate immediately after birth due to congenital complete atrioventricular
      block. At a gestational age of 29 weeks the patient was delivered by cesarean
      section followed by unsuccessful drug treatment of the atrioventricular block.
      Sixty-five minutes after birth the patient underwent permanent pacemaker
      implantation. Through a subxyphoid approach, a lead was fixed to the epicardium
      of the right ventricle, and connected to a pulse generator inserted between the
      rectus abdominus muscle and posterior rectus sheath. The patient is alive and
      well 16 months after the operation without pacemaker failure.

PMID- 15875556
TI  - Cardiac tamponade due to intrapericardial rupture of an amebic liver abscess.
AB  - Pericardial abscess is rare in healthy individuals, especially the amebic type.
      We report a case of pericardial abscess and cardiac tamponade due to
      intrapericardial rupture of an amebic liver abscess. A 31-year old Japanese male
      complained of fever to a local hospital. A liver mass was discovered in his left
      hepatic lobe by an abdominal echogram. He was referred to the internal department
      of our hospital and was treated with quinolone antibiotics. Two weeks after
      medication, he suddenly complained of epigastralgia and severe orthopnea and was
      admitted. Abdominal computed tomographic scan showed an enlarged liver mass, and
      massive pericardial effusion suggested cardiac tamponade. He underwent an
      emergency subxiphoid partial pericardiectomy under local anesthesia. 1,000 ml of
      light brownish fluid was removed and his condition improved. Although no ameba
      was cultivated from the pus, the amebic serological test was positive.
      Metronidazole was administered and the patient was discharged 31 days after
      surgery.

PMID- 15875555
TI  - Surgical closure of an apical ventricular septal defect through a septal
      ventriculotomy.
AB  - Here we report a 3-year and 7-month-old boy with a muscular ventricular septal
      defect at the apex. At age 7 months, pulmonary artery banding was performed.
      Surgical treatment consisted of double patch closure via septal ventriculotomy
      and a main pulmonary artery plasty by an end-to-end anastomosis with
      cardiopulmonary bypass. There was no residual leak of the ventricular septal
      defect or ventricular aneurysm and the postoperative course was good. This
      technique could be a useful surgical option for repair of apical muscular
      ventricular septal defects.

PMID- 15875557
TI  - Ossifying cardiac myxoma with neovascularity.
AB  - We report a 64-year-old man with ossifying cardiac myxoma which radiographically
      demonstrated visible calcification. A lateral chest radiograph showed abnormal
      calcification in the cardiac shadow. Two-dimensional and transesophageal
      echocardiography revealed a heterogeneous mass with a hyperechoic lesion in the
      left artium. A coronary angiogram showed a neovascular formation extending from
      the coronary arteries to the tumor. The resected tumor was composed of round or
      spindle shaped cells with myxoid stroma, accompanied by extensive calcification
      and ossification containing fatty and hematopoietic marrow tissue. Although a
      left atrial calcified myxoma is less common than a right sided myxoma, and such
      radiographically detectable calcified tumors are rare, the presence of
      radiographic visualized calcification in the cardiac shadow should be ruled out
      for left as well as right atrial myxomas.

PMID- 15875558
TI  - Bidirectional cavopulmonary shunt using the azygos vein.
AB  - A case is described in which a two-year-old boy, diagnosed with common
      atrioventricular canal, pulmonary atresia, major aortopulmonary collateral
      artery, asplenia, and situs inversus, underwent palliative operations for the
      following: unifocalization of the right major aortopulmonary collateral artery,
      right ventricle-to-pulmonary artery shunt, and pulmonary artery plasty. Upon
      completion of the bidirectional cavopulmonary shunt operation, we addressed the
      stenotic lesions of the superior vena cava and left pulmonary artery, and a
      markedly expanded azygos vein. During this operation, the superior vena cava was
      divided and we performed cavopulmonary shunting with the azygos vein.

PMID- 15875559
TI  - Re-reconstruction of visceral arteries with thoracoabdominal aortic replacement
      using a branched graft.
AB  - A 44-year-old man, unaffected by Marfan's syndrome, had previously undergone
      thoracoabdominal replacement for a chronic, type B dissecting aneurysm.
      Reconstruction of the visceral arteries was performed using an island technique.
      However, approximately 3 years after the operation, the reconstructed part of the
      aorta containing the visceral arteries became dilated and an aneurysm formed. We
      have succeeded both in repairing the aneurysms and "re-reconstructing" the
      visceral arteries using a branched graft. We conclude that the technique of
      separate revascularization is worth considering from the beginning, even if the
      patient does not present with Marfan's syndrome.

PMID- 15875560
TI  - Successful surgical treatment for acute aortic dissection in pregnancy with
      Marfan's syndrome.
AB  - A 34-year-old pregnant woman with Marfan's syndrome in the 34th week of gestation
      was diagnosed with acute DeBakey type I aortic dissection. Immediately after
      cesarean section, she underwent emergent operation of combined total aortic arch
      and aortic root replacement using cardiopulmonary bypass, deep hypothermia and
      antegrade cerebral perfusion. Both maternal and fetal outcomes were good and
      uneventful. Pregnancy increases the risk of aortic dissection especially for
      patients with Marfan's syndrome. Moreover it should be noted that cardiac surgery
      using cardiopulmonary bypass and deep hypothermia generally results in fetal
      loss. If fetal maturity can be confirmed as in our case, cesarean section should
      be done before cardiovascular surgery. We describe here a case of successful
      operation for mother and infant at the 34th week of gestation.

PMID- 15875561
TI  - Successful surgical treatment for an adult case of double aortic arch.
AB  - We present the case of a 39-year-old male who had complaints of dysphagia and
      throat pain. Computed tomography (CT), 3 dimensional CT and aortography revealed
      a double aortic arch (Edwards type IA). The patient underwent exploration through
      a left-sided thoracotomy and the left arch was divided at the distal site of the
      left subclavian artery, which completely relieved the esophageal compression.

PMID- 15875562
TI  - Thoracoabdominal coarctation of the aorta: surgical repair in a 7-year-old boy.
AB  - Atypical coarctation of the lower descending or the abdominal aorta is a
      relatively rare disease which occurs in about 0.5 to 2% of all coarctation cases.
      The majority of these diseases present with circumscribed narrowing of the
      abdominal aorta. However, we treated a 7-year-old boy with a rare form: a long,
      diffuse hypoplasia of the thoracoabdominal aorta.

PMID- 15875563
TI  - Anterior spinal artery syndrome after minimally invasive direct coronary artery
      bypass grafting under general combined epidural anesthesia.
AB  - A 65-year-old patient with ischemic heart disease and severe diabetes mellitus
      underwent minimally invasive direct coronary artery bypass grafting under general
      combined with epidural anesthesia. Paraplegia developed after surgery and the
      diagnosis of anterior spinal artery syndrome was made based on the patient's
      neurological condition and magnetic resonance imaging findings. Paraplegia
      following epidural anesthesia is a rare but recognized complication and this
      complication should be taken into account, especially in patients at risk, when
      considering epidural analgesia techniques in the minimally invasive cardiac
      surgery.

PMID- 15875565
TI  - Homing pigeons develop local route stereotypy.
AB  - The mechanisms used by homing pigeons (Columba livia) to navigate homeward from
      distant sites have been well studied, yet the mechanisms underlying navigation
      within, and mapping of, the local familiar area have been largely neglected. In
      the local area pigeons pote ntially have access to a powerful navigational aid--a
      memorized landscape map. Current opinion suggests that landmarks are used only to
      recognize a familiar start position and that the goalward route is then achieved
      solely using compass orientation. We used high-resolution global positioning
      system (GPS) loggers to track homing pigeons as they became progressively
      familiar with a local homing task. Here, we demonstrate that birds develop highly
      stereotyped yet individually distinctive routes over the landscape, which remain
      substantially inefficient. Precise aerial route recapitulation implies close
      control by localized geocentric cues. Magnetic cues are unlikely to have been
      used, since recapitulation remains despite magnetic disruption treatment, and
      olfactory cues would have been positionally unstable under the variable wind
      conditions, making visual landmarks the most likely cues used.

PMID- 15875564
TI  - Ancient DNA.
AB  - In the past two decades, ancient DNA research has progressed from the retrieval
      of small fragments of mitochondrial DNA from a few late Holocene specimens, to
      large-scale studies of ancient populations, phenotypically important nuclear
      loci, and even whole mitochondrial genome sequences of extinct species. However,
      the field is still regularly marred by erroneous reports, which underestimate the
      extent of contamination within laboratories and samples themselves. An improved
      understanding of these processes and the effects of damage on ancient DNA
      templates has started to provide a more robust basis for research. Recent
      methodological advances have included the characterization of Pleistocene mammal
      populations and discoveries of DNA preserved in ancient sediments. Increasingly,
      ancient genetic information is providing a unique means to test assumptions used
      in evolutionary and population genetics studies to reconstruct the past. Initial
      results have revealed surprisingly complex population histories, and indicate
      that modern phylogeographic studies may give misleading impressions about even
      the recent evolutionary past. With the advent and uptake of appropriate
      methodologies, ancient DNA is now positioned to become a powerful tool in
      biological research and is also evolving new and unexpected uses, such as in the
      search for extinct or extant life in the deep biosphere and on other planets.

PMID- 15875566
TI  - Handedness, homicide and negative frequency-dependent selection.
AB  - Humans exhibit hand preference for most manual activities in which they are
      specialized. Right- and left-handers have coexisted at least since the Upper
      Palaeolithic, and left-handers are in the minority in all human populations. The
      persistence of the polymorphism of handedness is a puzzle because this trait is
      substantially heritable and several fitness costs are associated with left
      handedness. Some countervailing benefit is required to maintain the polymorphism.
      Left-handers may have a frequency-dependent advantage in fights--the advantage
      being greater when their frequency is lower. Sports data from Western societies
      are consistent with this prediction. Here, we show that the frequency of left
      handers is strongly and positively correlated with the rate of homicides across
      traditional societies. It ranges from 3% in the most pacifistic societies, to 27%
      in the most violent and warlike. This finding is consistent with a frequency
      dependent selection mechanism maintaining left-handedness in these societies.

PMID- 15875567
TI  - Are reproductive and somatic senescence coupled in humans? Late, but not early,
      reproduction correlated with longevity in historical Sami women.
AB  - Evolutionary theory of senescence emphasizes the importance of intense selection
      on early reproduction owing to the declining force of natural selection with age
      that constrains lifespan. In humans, recent studies have, however, suggested that
      late-life mortality might be more closely related to late rather than early
      reproduction, although the role of late reproduction on fitness remains unclear.
      We examined the association between early and late reproduction with longevity in
      historical post-reproductive Sami women. We also estimated the strength of
      natural selection on early and late reproduction using path analysis, and the
      effect of reproductive timing on offspring survival to adulthood and maternal
      risk of dying at childbirth. We found that natural selection favoured both
      earlier start and later cessation of reproduction, and higher total fecundity.
      Maternal age at childbirth was not related to offspring or maternal survival.
      Interestingly, females who produced their last offspring at advanced age also
      lived longest, while age at first reproduction and total fecundity were unrelated
      to female longevity. Our results thus suggest that reproductive and somatic
      senescence may have been coupled in these human populations, and that selection
      could have favoured late reproduction. We discuss alternative hypotheses for the
      mechanisms which might have promoted the association between late reproduction
      and longevity.

PMID- 15875568
TI  - Inbreeding uncovers fundamental differences in the genetic load affecting male
      and female fertility in a butterfly.
AB  - Inbreeding depression is most pronounced for traits closely associated with
      fitness. The traditional explanation is that natural selection eliminates
      deleterious mutations with additive or dominant effects more effectively than
      recessive mutations, leading to directional dominance for traits subject to
      strong directional selection. Here we report the unexpected finding that, in the
      butterfly Bicyclus anynana, male sterility contributes disproportionately to
      inbreeding depression for fitness (complete sterility in about half the sons from
      brother-sister matings), while female fertility is insensitive to inbreeding. The
      contrast between the sexes for functionally equivalent traits is inconsistent
      with standard selection arguments, and suggests that trait-specific developmental
      properties and cryptic selection play crucial roles in shaping genetic
      architecture. There is evidence that spermatogenesis is less developmentally
      stable than oogenesis, though the unusually high male fertility load in B.
      anynana additionally suggests the operation of complex selection maintaining male
      sterility recessives. Analysis of the precise causes of inbreeding depression
      will be needed to generate a model that reliably explains variation in
      directional dominance and reconciles the gap between observed and expected
      genetic loads carried by populations. This challenging evolutionary puzzle should
      stimulate work on the occurrence and causes of sex differences in fertility load.

PMID- 15875569
TI  - Why do multiple traits determine mating success? Differential use in female
      choice and male competition in a water boatman.
AB  - Mating success is often determined by multiple traits, but why this occurs is
      largely unknown. Much attention has been paid to female preferences for multiple
      traits, but surprisingly few researchers have addressed the possibility that
      multiple traits are important because they serve different functions in female
      choice and male-male competition. Differential trait function could result from a
      conflict of interest between the sexes or from constraints forcing the sexes to
      pay attention to different traits. I show that traits determined at distinct life
      history stages differ in their importance in female choice and male-male
      competition in a water boatman Sigara falleni. Juvenile conditions determined
      body and foreleg pala size and were the main determinants of mating success under
      female choice, whereas adult conditions determined body mass and influenced
      mating success when male competition was included. This differential use of
      condition-dependent traits under the two selection regimes appeared to arise
      partly from a conflict between the sexes, since the two selection forces (female
      choice and male competition) conflict for selection on pala size, and partly from
      constraints, as females appeared unable to assess adult condition.

PMID- 15875570
TI  - The three-dimensional flight of red-footed boobies: adaptations to foraging in a
      tropical environment?
AB  - In seabirds a broad variety of morphologies, flight styles and feeding methods
      exist as an adaptation to optimal foraging in contrasted marine environments for
      a wide variety of prey types. Because of the low productivity of tropical waters
      it is expected that specific flight and foraging techniques have been selected
      there, but very few data are available. By using five different types of high
      precision miniaturized logger (global positioning systems, accelerometers, time
      depth recorders, activity recorders, altimeters) we studied the way a seabird is
      foraging over tropical waters. Red-footed boobies are foraging in the day, never
      foraging at night, probably as a result of predation risks. They make extensive
      use of wind conditions, flying preferentially with crosswinds at median speed of
      38 km h(-1), reaching highest speeds with tail winds. They spent 66% of the
      foraging trip in flight, using a flap-glide flight, and gliding 68% of the
      flight. Travelling at low costs was regularly interrupted by extremely active
      foraging periods where birds are very frequently touching water for landing,
      plunge diving or surface diving (30 landings h(-1)). Dives were shallow (maximum
      2.4 m) but frequent (4.5 dives h(-1)), most being plunge dives. While chasing for
      very mobile prey like flying fishes, boobies have adopted a very active and
      specific hunting behaviour, but the use of wind allows them to reduce travelling
      cost by their extensive use of gliding. During the foraging and travelling phases
      birds climb regularly to altitudes of 20-50 m to spot prey or congeners. During
      the final phase of the flight, they climb to high altitudes, up to 500 m,
      probably to avoid attacks by frigatebirds along the coasts. This study
      demonstrates the use by boobies of a series of very specific flight and activity
      patterns that have probably been selected as adaptations to the conditions of
      tropical waters.

PMID- 15875572
TI  - Natural selection on mitochondrial DNA in Parus and its relevance for
      phylogeographic studies.
AB  - I examined mitochondrial ND2 sequences in species of tits (genus Parus) to
      determine whether substitutions were neutral or under selection. Haplotype trees
      in these species are shallow and geographically unstructured, which could be a
      signature of recent demographic expansion or purifying selection. McDonald
      Kreitman tests revealed a pattern of excess replacement polymorphisms for closely
      related taxa. Replacement substitutions tended to be less common in the basal
      parts of haplotype trees, suggesting that they are selected against over
      evolutionary time. Thus, the pattern of selection is consistent with a model of
      mildly deleterious haplotypes. To investigate the significance of this selection,
      the ND2 gene was subdivided into surface and transmembrane portions, and
      synonymous-non-synonymous sites, and F(ST)-values (the amount of variance
      distributed among populations) computed for each. Among sampling localities in P.
      major, both partitions gave similar estimates of F(ST), which is consistent with
      demographic expansion as the cause of the shallow trees. In P. montanus, two
      localities contained high percentages of individuals that had a single
      replacement substitution in the transmembrane portion of the gene, which inflated
      F(ST)-values relative to the surface sites. Thus, the interpretation of the
      genetic differentiation of these two sites could be either geographical isolation
      or selection. Given that the sole substitution causing the high F(ST)-values was
      a replacement one, selection is implicated. However, this substitution occurred
      in only 2 of 12 localities, revealing that overall the phylogeographic pattern
      was not biased by selection, once the cause of the two high pairwise F(ST)
      comparisons was recognized. Investigators should consider the source of
      significant genetic heterogeneity within species, to determine if the variation
      is likely caused by demographic isolation or selection. However, it seems
      unlikely that most phylogeographic analyses are invalidated by the effects of
      natural selection.

PMID- 15875571
TI  - Juvenile immune system activation induces a costly upregulation of adult immunity
      in field crickets Gryllus campestris.
AB  - Inducible immune defence may allow organisms a state-dependent upregulation of
      costly immunity in order to minimize the risk of anticipated future parasitism.
      The basic costs of elevated immune activity might involve a reduction in other
      fitness-related traits as well as an increased risk of immunopathology. In male
      field crickets Gryllus campestris we experimentally investigated the condition
      dependent effects of immune system activation in nymphs on immunity and
      physiological condition during adulthood. Following a nymphal injection of
      bacterial lipopolysaccharides, adult males showed significantly elevated levels
      of two major immune parameters, i.e. haemolymph antibacterial activity and the
      concentration of prophenoloxidase (proPO). By contrast, the active enzyme,
      phenoloxidase (PO), did not increase, suggesting a strategic long-term
      upregulation of the inactive proenzyme proPO only. This may help avoid the
      cytotoxic effects associated with high standing levels of the active enzyme. The
      nymphal immune insult further caused a reduction in adult haemolymph protein
      load, suggesting a long-term decline in overall metabolic condition. Nymphal food
      availability positively affected adult lysozyme activity, while PO and proPO
      concentrations were not affected. Our data thus suggest the long-term
      upregulation of immunity in response to antigenic cues as an adaptive, yet
      costly, invertebrate strategy to improve resistance to future parasitism.

PMID- 15875573
TI  - Group-beneficial traits, frequency-dependent selection and genotypic diversity:
      an antibiotic resistance paradigm.
AB  - The evolution of group-beneficial traits potentially allows the survival of
      'cheaters' that would otherwise be unfit. Here we describe experimental work on
      group-beneficial traits and the consequences of frequency-dependent selection in
      the context of bacterial antibiotic resistance. We constructed a 'self-limited
      antibiotic resistant' (SLAR) strain of Escherichia coli in which a TEM-1 beta
      lactamase was anchored to the inner membrane. In pairwise competition experiments
      between the SLAR strain and ampicillin-sensitive strains, only the SLAR strain
      survived in the presence of ampicillin. We also constructed a 'shared antibiotic
      resistant' (SAR) strain in which TEM-1 beta-lactamase protected both the SAR
      strain and nearby sensitive cells, thus acting as a model for a genetically
      defined group-beneficial trait. In pairwise competition experiments of the SAR
      strain against two different sensitive strains of E. coli, we found that the
      sensitive strains maintained themselves at frequencies of 5-12% in the presence
      of ampicillin. When the relative cost of the SAR strain was lowered, its
      equilibrial frequency rose. Sensitive strains also arose from pure cultures of
      the SAR strain. In these cases, too, the sensitive 'cheaters' were maintained in
      ampicillin at frequencies comparable to those observed in the previous
      competitions. These results suggest that traits which benefit other group members
      can permit survival of genotypes that otherwise would be eliminated by natural
      selection, and allow the maintenance of greater genetic variation upon which
      evolution can operate.

PMID- 15875574
TI  - Adaptation to the cost of resistance: a model of compensation, recombination, and
      selection in a haploid organism.
AB  - Populations of pathogenic organisms often evolve resistance in response to the
      use of pesticides or antibiotics. This rise of resistance may be followed by a
      fall when chemical control is suspended and resistance alleles carry a fitness
      cost. Another possibility is that mutations at secondary loci compensate for the
      cost, usually without loss of resistance. This enables resistant types to
      withstand invasion by the susceptible wild-type; resistance then persists in the
      population, which reduces the efficacy of future pesticide or antibiotic use. We
      examined a two-locus model of a haploid organism that adapts to the cost of
      resistance by a single compensatory mutation. We addressed the question how
      different combinations of cost and compensation and different levels of
      recombination affect the consequences of a single pesticide application.
      Resistance will become fixed in the population when the fraction of the
      population exposed to pesticide exceeds the cost of resistance. Compensatory
      mutations reduce the cost of resistance and therefore this threshold level of
      pesticide use. In the absence of pesticide, recombination promotes stability of
      equilibria. In the presence of pesticide, recombination accelerates the fixation
      of resistance and compensating alleles; recombination may also enable the
      persistence of compensated resistant types after pesticide use.

PMID- 15875576
TI  - Theta oscillations by synaptic excitation in a neocortical circuit model.
AB  - Neocortical theta-band oscillatory activity is associated with cognitive tasks
      involving learning and memory. This oscillatory activity is proposed to originate
      from the synchronization of interconnected layer V intrinsic bursting (IB)
      neurons by recurrent excitation. To test this hypothesis, a sparsely connected
      spiking circuit model based on empirical data was simulated using Hodgkin-Huxley
      type bursting neurons and use-dependent depressing synaptic connections. In
      response to a heterogeneous tonic current stimulus, the model generated coherent
      and robust oscillatory activity throughout the theta-band (4-12 Hz). These
      oscillations were not, however, self-sustaining without a driving current, and
      not dependent on N-methyl-D-aspartate receptor synaptic currents. At realistic
      connection strengths, synaptic depression was necessary to avoid instability and
      expanded the basin of attraction for theta oscillations by controlling the gain
      of recurrent excitation. These results support the hypothesis that IB neuron
      networks can generate robust and coherent theta-band oscillations in neocortex.

PMID- 15875578
TI  - Building a new beginning. Interview by Sarah Harrison.

PMID- 15875575
TI  - Peripheral variability and central constancy in mammalian visual system
      evolution.
AB  - Neural systems are necessarily the adaptive products of natural selection, but a
      neural system, dedicated to any particular function in a complex brain, may be
      composed of components that covary with functionally unrelated systems, owing to
      constraints beyond immediate functional requirements. Some studies support a
      modular or mosaic organization of the brain, whereas others emphasize
      coordination and covariation. To contrast these views, we have analysed the
      retina, striate cortex (V1) and extrastriate cortex (V2, V3, MT, etc.) in 30
      mammals, examining the area of the neocortex and individual neocortical areas and
      the relative numbers of rods and cones. Controlling for brain size and species
      relatedness, the sizes of visual cortical areas (striate, extrastriate) within
      the brains of nocturnal and diurnal mammals are not statistically different from
      one another. The relative sizes of all cortical areas, visual, somatosensory and
      auditory, are best predicted by the total size of the neocortex. In the sensory
      periphery, the retina is clearly specialized for niche. New data on rod and cone
      numbers in various New World primates confirm that rod and cone complements of
      the retina vary substantially between nocturnal and diurnal species. Although
      peripheral specializations or receptor surfaces may be highly susceptible to
      niche-specific selection pressures, the areal divisions of the cerebral cortex
      are considerably more conservative.

PMID- 15875579
TI  - Head to head--the gloves are off.
AB  - This article explores key issues in nursing through the eyes of commentator
      Harriet Sergeant and nursing leader Beverly Malone. In a question and answer
      session, they address nursing's current hot topics

PMID- 15875580
TI  - Charge ahead.
AB  - The system of prescription charges is in disarray, with Wales and Scotland
      introducing systems that are different to those operating in England. The cost of
      prescriptions means some people take a lower dose than that prescribed or do not
      take their drugs at all.

PMID- 15875582
TI  - Breaking the taboo.
AB  - Carole Stone is the first mobile nurse in the community for leading bowel cancer
      charity Colon Cancer Concern. She says the past five years have seen exciting
      developments in treatment of the disease but bowel cancer is still a taboo
      subject.

PMID- 15875583
TI  - Separate lives.

PMID- 15875584
TI  - Communicating news of patients' deaths to unrelated stem cell donors.
AB  - AIM: To identify the most appropriate method of breaking news of a patient's
      death to unrelated stem cell donors, and to establish best practice guidelines
      based on the findings. METHOD: In this retrospective study, 100 unrelated stem
      cell donors from the Welsh Bone Marrow Donor Registry were interviewed regarding
      their experiences of receiving news of a patient's death. results were analysed
      by counting responses to the interview schedule, and identifying common themes
      from the open comments. RESULTS: Of the 100 participants, 78 had been informed of
      the patient's death by letter and 22 by telephone with the option of a follow-up
      letter. Overall, 61 per cent (n=61) of donors interviewed preferred to be
      contacted by telephone, 25 per cent (n=25) by letter and 13 per cent (n=13) by
      face-to-face contact at a visit. CONCLUSION: There is no easy way to break bad
      news, and each individual responds to grief in a unique way. By building up a
      trusting relationship with the donor, the healthcare professional can assess the
      individual to ascertain which method of receiving news of a patient's death would
      be most appropriate.

PMID- 15875585
TI  - Documentation in nursing practice.
AB  - Accurate documentation is essential to maintain continuity and inform health
      professionals of ongoing care and treatment. It also provides legal evidence.
      This article highlights the advantages of accurate record keeping and the
      barriers to effective documentation in the community setting.

PMID- 15875586
TI  - Avoiding relapse in behaviour change.
AB  - This article, the third of eight in the health promotion series, aims to offer
      nurses strategies to help clients avoid relapsing into previous behaviour
      patterns following a lifestyle change.

PMID- 15875587
TI  - Understanding sickle cell disorders.
AB  - More than 12,500 people in England have sickle cell disorders. This article
      explains how these disorders call be inherited and discusses the associated
      clinical problems. The author focuses on social, psychosocial and cultural
      aspects, and the implications for nursing practice are examined.

PMID- 15875588
TI  - Diabetic emergencies.

PMID- 15875589
TI  - Assessment and management of patients with leg ulcers.
AB  - This article discusses the assessment and management of patients with leg ulcers,
      focusing on venous, arterial and mixed aetiology ulcers. Successful care planning
      should be based on working in partnership with patients in terms of offering
      choices that meet their clinical, quality-of-life and psychosocial needs.

PMID- 15875590
TI  - The development of a nurse-led complex wound clinic.
AB  - This article describes the development of a nurse-led complex wound clinic in
      Lincolnshire in April 2003, and describes one patient's experience of the
      service. It also explores the benefits of collaborative initiatives that have the
      potential to improve patient outcomes.

PMID- 15875592
TI  - Breath of fresh air.

PMID- 15875591
TI  - Inter-rater reliability and Waterlow's pressure ulcer risk assessment tool.
AB  - AIM: To ascertain whether a lack of inter-rater reliability with the original
      Waterlow (1996) pressure ulcer risk assessment scale is due to different
      perceptions of patients by nurses or different interpretations of Waterlow as a
      tool. METHOD: A sample of 110 qualified nurses, who used the Waterlow pressure
      ulcer risk assessment scale in their daily work and were delegates at five study
      days, were given a case study and an uncompleted copy of the tool. They were
      asked to complete a risk assessment for the patient. The risk assessment score
      obtained by delegates was analysed using the Wilcoxon Signed Rank Test to measure
      the null hypothesis that there is no significant difference between the median of
      the nurses' scores and the patient's actual or 'gold standard' score. RESULTS:
      Nurses tend to over-rate (n=72, 65 per cent) rather than under-rate (n=25, 23 per
      cent) the patient's risk of developing a pressure ulcer. Only 13 of the 110
      nurses (12 per cent) accurately rated the patient's score as 18. The Wilcoxon
      Test rejected the null hypothesis that there was no difference in the risk scores
      arrived at by individual nurses and the patient's actual score, that is, there is
      a significant difference between the scores obtained by the nurses in the study
      and the gold standard score. CONCLUSION: The results show poor inter-rater
      reliability when using the Waterlow pressure ulcer risk assessment scale. Part of
      the problem is that nurses are not using the tool in the way it was intended.

PMID- 15875594
TI  - Insulin.

PMID- 15875595
TI  - What is the cure for the nation's hangover?

PMID- 15875596
TI  - Parents offered anger management lessons.

PMID- 15875597
TI  - Early intervention and mental health.

PMID- 15875598
TI  - Health work in the Himalayas.

PMID- 15875599
TI  - Falls prevention in older people.

PMID- 15875600
TI  - ADHD: assessment and intervention.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common
      psychiatric disorders of childhood. Although there is a lot of debate and
      controversy over the recognition of ADHD, it is generally accepted nowadays as a
      clinical disorder that may warrant treatment Children with ADHD are pervasively
      overactive, fidgety and disruptive. They have impaired attention and
      concentration and are impulsive. These symptoms have serious implications for the
      child's relationships with parents, siblings and peers. It is important that
      community practitioners, school nurses, health visitors and other health
      professionals are able to recognise the condition and be able to make an informed
      clinical assessment and refer and manage accordingly. The assessment should
      include a clear history from parents, a school report and an individual interview
      with the child. An assessment of parental management is essential to avoid the
      child being wrongly diagnosed with the condition. The successful intervention
      should be aimed at educating the child and family about the disorder and
      psychosocial interventions that may help the family and school cope with the
      child. In some cases introduction of medication may be necessary.

PMID- 15875601
TI  - Lay perceptions of health and health needs.
AB  - The accurate identification of need is imperative to maximise population health
      gains and target health inequalities. Social capital, expressed in social,
      psychological, economic and contextual factors, acts as a buffer in communities.
      The aim of this study was to determine the unexpressed health needs of a
      population. A needs analysis was undertaken, using Community Participatory
      Appraisal methodology, to determine the lay perspective in a rural village. Semi
      structured face-to-face interviews with 11 adults were conducted followed by a
      focus group of seven adults. A questionnaire was developed and posted to 350
      adults randomly selected within stratified categories from the general practice
      surgery list. The predominant feature of the interviews and focus group was that
      the divided nature of the village impinged on social cohesion and the health of
      the population. Of the questionnaire results 63% reported good health. Other
      findings were the lower educational achievement and life expectations in the
      social housing area, and the level of psychological distress among males,
      particularly in the 18 to 25 age group. Information on health needs can be
      determined from the lay perspective. To target a population for public health
      initiatives, it is important to gather data pertinent to the specific community.
      The study demonstrated that knowledge is held by individuals that can be used to
      inform direction of travel and more accurate service provision. This paper is the
      first of two; the first reports the research and the second describes the
      implementation of some of the results of the study.

PMID- 15875602
TI  - Why do nurses enter community and public health practice?
AB  - Current policy places much emphasis on public health and care outside hospital.
      To provide this requires a qualified work force but a large number of community
      nurses are approaching retirement. While there is a commitment to recruit and
      retain such nurses, there is little information available on community nurses'
      career trajectories, or on why staff choose to work in the community and why they
      undertake community specialist practice (CSP) programmes. This paper reports the
      findings of a survey of community specialist practice students--community
      children's nurses (CCNs), community mental health nurses (CMHNs) district nurses
      (DNs), health visitors (HVs), practice nurses (PNs), school nurses (SNs)--in a
      large London based programme. They were asked why they had entered community
      practice and why they had undertaken a community specialist practice programme.
      Findings were not categorical; the reasons for entering community work included
      increased initiative, more autonomy and preferred hours. Scope for initiative,
      autonomy and increased independence were reasons for undertaking the CSP
      programme, as well as better promotion prospects. Differences were evident in
      response by age of respondent and by whether they had dependent children. All
      types of respondents saw themselves as public health practitioners. Practice
      nurses stood out as different from the others, seeing hours as significant, but
      not promotion prospects despite expecting higher grades on completion of the
      programme. The study raises various questions, which could be explored after
      refinement of the study tool and using students in different locations throughout
      the country.

PMID- 15875603
TI  - Childhood obesity: prevention, treatment and recommendations for health.

PMID- 15875604
TI  - Getting right back to the basics.

PMID- 15875605
TI  - Caution urged over 'assuming' consent.

PMID- 15875606
TI  - Case reports.

PMID- 15875607
TI  - Ezetimibe-induced hyperlipidaemia.
AB  - Ezetimibe is intestinally active cholesterol absorption inhibitor used to reduce
      low-density lipoprotein-cholesterol levels. This case report describes a novel
      side effect with this agent: ezetimibe-induced hyperlipidaemia in a patient with
      statin intolerance and familial combined hyperlipidaemia. Ezetimibe therapy
      induced an asymptomatic 770% increase in triglycerides (TGs) (3.51-27.1 mmol/l)
      and a 190% increase in total cholesterol (9.8-18.5 mmol/ 1) secondary to an
      increase (4.6-25.9 micromol/l; 560%) in hepatic cholesterol (lathosterol)
      synthesis. This lipid profile resolved 9 months after cessation of ezetimibe
      therapy. This report shows that ezetimibe may have long-lasting effects in man
      far exceeding its plasma half-life and that ezetimibe monotherapy can induce a
      large increase in hepatocyte very-low-density lipoprotein synthesis in rare
      individuals with a consequent mixed hyperlipidaemia or possibly
      hypercholesterolaemia depending on the metabolism and clearance of TG-rich
      lipoproteins.

PMID- 15875608
TI  - Aortic valve endocarditis presents as pseudoaneurysm of the superior mesenteric
      artery.
AB  - Mycotic aneurysms are an important cause of morbidity and mortality in
      endocarditis despite advanced antibiotic therapy. Visceral artery aneurysms are
      uncommon and usually remain clinically silent until rupture. We now report a case
      of successful surgical treatment of a superior mesenteric mycotic aneurysm of the
      superior mesenteric artery, followed by a review of pertinent clinical
      information.

PMID- 15875609
TI  - Heart failure due to giant congenital aorto-right atrial fistula: report of a
      case.
AB  - Coronary arterio-venous fistula (CAVF) is a rare coronary artery anomaly. We
      demonstrated the rare findings of a large congenital aorto-right atrial fistula
      with initial presentation of heart failure symptoms. Transthoracic
      echocardiography and transesophageal echocardiography made the accurate
      diagnosis. Further haemodynamic and angiographic study proved this large CAVF
      with extraordinary oxygen saturation step-up (26%) and large pulmonary to
      systemic shunt (Qp/Qs = 4.25). It was corrected by surgery because of evidence of
      heart failure and the possible risk of endocarditis and coronary steal effect.

PMID- 15875610
TI  - The transient appearance of collateral circulation during coronary spasm.
AB  - This article reports a case of transient augmentation of collateral circulation
      due to spontaneous coronary arterial spasm during angiography. The patient's
      electrocardiogram revealed ST-segment depression during vasospastic attack; this
      depression differs from the typical change of the ST-segment elevation in
      coronary spasm without collateral circulation.

PMID- 15875611
TI  - Sudden death in Wolff-Parkinson-White syndrome combined with syncope: a case
      report.
AB  - Electrocardiogram showing Wolff-Parkinson-White (WPW) pattern in an asymptomatic
      patient is common, but it is difficult to assess the potential risk of sudden
      death in such cases. Although the incidence of sudden death in these patients is
      extremely low, an interventional approach is suggested for all patients despite
      its controversial nature. Syncope, despite being induced by various mechanisms,
      has been considered an alarming sign of sudden death of WPW syndrome. We describe
      a 16-year-old female patient with an electrocardiogram that demonstrated a WPW
      pattern combined with unexplained syncope. None of the examinations, including
      biochemical profiles, brain computed tomography, transthoracic echocardiography,
      head-up tilt table test and exercise electrocardiogram, clarified her syncope.
      Consequently, no further electrophysiologic study was performed for this patient.
      Unfortunately, the patient suffered sudden death while running. The case
      highlights the need for vigilance when unexplained syncope combined with WPW
      syndrome. Such cases have high risk of sudden death, and thus, further
      interventional study and treatment is indicated.

PMID- 15875612
TI  - Exercise-induced myocardial ischaemia complicated by paroxysmal complete
      atrioventricular block.
AB  - This study describes a case of exercise-induced myocardial ischaemia accompanied
      by complete atrioventricular block (CAVB). A 59-year-old man with major
      depression, treated with regular imipramine and lithium for 20 years, experienced
      syncope episodes during exercise. Exercise, testing initially, identified ST
      depression in the inferior leads, and later found CAVB resulting in syncope and
      seizure. The patient recovered completely after resuscitation. Myocardial
      ischaemic markers were negative, but 35% stenosis was detected in the distal left
      main coronary artery by angiography. The combined use of verapamil, nitrate and
      aspirin was treated as the possible coronary spasm. Repeat treadmill caused
      negative ischaemic study or exercise-induced arrhythmia, 7 days later. The
      pathophysiology of the very rare exercise-induced paroxysmal CAVB has been
      reviewed.

PMID- 15875613
TI  - Mesothelial/monocytic incidental cardiac excrescences of the heart: case report
      and literature review.
AB  - Mesothelial/monocytic incidental cardiac excrescences (MICE) of the heart are
      rare benign entities that have only been diagnosed incidentally, following
      cardiac surgical procedure. To date, totally 35 cases have been reported in the
      English literature. We describe an additional case of cardiac MICE presenting
      with severe aortic regurgitation for aortic valve replacement in a 20-year-old
      Chinese male patient. On microscopic examination, the findings initially were
      confused with true neoplasm. However, the related gross appearance, clinical
      history and further immunohistochemical staining enabled an accurate diagnosis.
      We review the relevant literature and found that immunohistochemical staining,
      especially the anti-cytokeratin antibody (AE1/AE3) and KP1 (CD-68) that were used
      by most investigators previously, was significant while making the diagnosis,
      because the two components of the cells show a contrast immunoreactivity to these
      two makers. The pathologists should always be alert to this entity while diagnose
      a cardiac surgery specimen.

PMID- 15875614
TI  - A case report: isolated a heavy chain monoclonal gammopathy in a patient with
      polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin
      change syndrome.
AB  - A 45-year-old South-Korean man presented with abdominal distension, progressive
      paresthesia and motor weakness of both lower extremities. Our case was identified
      as polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin
      change (POEMS) syndrome based on diagnostic criteria. Circulating M components of
      POEMS syndrome consist mainly of IgG or IgA-lambda and rarely IgM-lambda, IgG
      kappa or isolated light chains. In this case, the M-band on serum protein
      electrophoresis and isolated IgA heavy chain on serum immunofixation
      electrophoresis were demonstrated, but there was no abnormal light chain. We
      suggest that this case may be associated with a pattern of abnormal secretion of
      monoclonal protein or a coincidence of a heavy chain disease in POEMS syndrome,
      even though the latter possibility may be very rare.

PMID- 15875615
TI  - Hypothyroidism--an unexpected diagnosis following emergency treatment for
      heatstroke.
AB  - Heat illness is a common presentation to emergency departments during periods of
      high ambient temperatures. The thyroid axis is involved in thermoregulation, and
      its dysfunction dysfunction leads to loss of thermal homeostasis. Hyperthyroidism
      predisposes an individual to heat illness and hypothyroidism to hypothermia. For
      heat illness to be the presenting feature of hypothyroidism is very rare. In this
      report, a case is presented and a discussion of the thyroid axis,
      thermoregulation, its failure and possible mechanisms follows on.

PMID- 15875616
TI  - A case of excess growth hormone levels.
AB  - Patients with anorexia nervosa are known to have elevated basal growth hormone
      levels, which fail to suppress normally during glucose tolerance testing. We
      describe a case of probable anorexia nervosa initially diagnosed as acromegaly
      despite a low insulin-like growth factor-1 level and treated with transsphenoidal
      surgery based on a pituitary microadenoma on magnetic resonance imaging and a
      lack of suppression of growth hormone levels during glucose tolerance testing.
      This case highlights, firstly, that pituitary magnetic resonance imaging will
      suggest a pituitary adenoma in up to 10% of normal individuals. Secondly, that a
      diagnosis of acromegaly should be made on clinical features as well as growth
      hormone measurements.

PMID- 15875617
TI  - The clinical significance of gas-containing liver abscesses converting from total
      gas content to gas and fluid content: a case report.
AB  - The first case of gas-containing liver abscesses converting from total gas
      content to gas and fluid content is reported, and the clinical significance of
      such a conversion is emphasised. A 58-year-old diabetic woman suffered from fever
      and chill due to totally gas-containing liver abscesses shown by computerised
      tomography (CT). The patient did not recover despite ultrasound-guided aspiration
      of the abscess. CT carried out 2 weeks later revealed that the initial totally
      gas-containing liver abscesses converted to ones with gas and fluid content. The
      patient recovered after CT-guided drainage of the abscesses.

PMID- 15875618
TI  - An increase in creatine kinase secondary to acute pancreatitis: a case report.
AB  - Creatine kinase (CK) activity is found in high concentrations in skeletal muscle,
      cardiac muscle and brain. Here, we describe a 64-year-old woman with acute
      pancreatitis and elevated serum CK activity. This association is extraordinarily
      rare. In particular, laboratory findings which were found to be abnormal were
      serum CK 4.150 U/l (peaked 1 day after admission) with the CK-MB fraction being
      less than 5%, lactate dehydrogenase (LDH) 424 U/l, serum lipase 1.265 U/I and
      serum amylase 1.105 U/l. Some data regarding the phenomenon of acute pancreatitis
      and elevated serum CK activity are given.

PMID- 15875619
TI  - Spontaneous rupture of the cervical oesophagus following nose blowing: a case
      report.
AB  - Spontaneous rupture of the oesophagus is a rare event. Most have been reported in
      association with oesophageal carcinoma, peptic ulceration and alcohol abuse
      followed by forceful episode of vomiting. We, however, report a case of
      spontaneous rupture of the oesophagus in an otherwise healthy individual with no
      history of alcohol intake, as a consequence of blowing of the nose.

PMID- 15875620
TI  - Acute mediastinitis resulting from an unsuspected fish bone--case report.
AB  - Acute mediastinitis is a serious medical condition with a mortality rate from 30
      to 40% or even higher. Early diagnosis with prompt and aggressive treatment is
      essential to prevent its rapid progression. Severe odynophagia and respiratory
      distress with positive neck or chest findings should raise suspicion of
      mediastinitis. We report a rare case of acute mediastinitis secondary to the
      unexpected migration of an impacted fish bone from the esophagus.

PMID- 15875621
TI  - Genetic haemochromatosis presenting as porphyria cutanea tarda.
AB  - Porphyria cutanea tarda (PCT) is the commonest form of porphyria. It can be
      inherited or acquired. We present a case of genetic haemochromatosis with
      associated PCT. Venesection led to improvement in both conditions. We highlight
      the need for the awareness of PCT and its associated conditions.

PMID- 15875622
TI  - Multiple, large, benign peritoneal cysts--a case report.
AB  - This case report describes a unique case of large (up to 17 cm!) peritoneal cysts
      of uncertain aetiology. It illustrates the diagnostic and management difficulties
      encountered with such a rare problem. Although subsequently proven to be benign,
      they were thought to represent an extreme form of endosalpingiosis after a
      literature review.

PMID- 15875623
TI  - Acute renal failure due to leukaemic infiltration in chronic lymphocytic
      leukaemia: case report.
AB  - A 73-year-old woman was presented with altered mental status and disorientation.
      She was diabetic and hypertensive, and she had experienced an ischemic
      cerebrovascular accident 3 years ago. Physical examination revealed the findings
      of chronic obstructive pulmonary disease, cor pulmonale and congestive heart
      failure. Hepatomegaly, splenomegaly and ascites were found and might be
      associated with postsinusoidal portal hypertension secondary to congestive heart
      failure. Laboratory tests showed uremia, lymphocytosis and thrombocytopenia.
      Neurologic findings were related with uremia and hypoxia. Multiple pathologic
      lymphadenopathies were seen in abdominal ultrasonography and thoracic computed
      tomography. Bone marrow histology indicated chronic lymphocytic leukaemia (CLL).
      The reason for acute renal failure was leukaemic infiltration of the kidneys due
      to CLL that was shown with renal biopsy. Blood urea nitrogen (BUN) and serum
      creatinine responded well to cyclophosphamide and methyl prednisolone treatment.
      In CLL, direct renal involvement is frequently seen in autopsy studies especially
      in advanced disease, however, renal failure due to leukaemic infiltration is
      extremely rare.

PMID- 15875624
TI  - Tuberculous peritonitis in a haemodialysis patient with elevated serum CA 125 and
      hypercalcaemia.
AB  - CA 125, a glycoprotein derived from coelomic epithelium, is used primarily as a
      marker of epithelial ovarian cancer. However, elevated levels of serum CA 125
      have also been detected in other benign and malignant disorders. This study
      describes a haemodialysis patient who contracted tuberculous peritonitis
      associated with hypercalcaemia, erythropoietin-resistant anaemia and elevated CA
      125, which normalised gradually following antituberculosis treatment. Tuberculous
      peritonitis should be considered in the differential diagnosis of ascites with
      elevated serum CA 125. Additionally, CA 125 is a useful marker for monitoring
      response to tuberculous peritonitis treatment.

PMID- 15875625
TI  - Meningitis associated with familial Mediterranean fever.
AB  - Neurologic involvement in patients with familial Mediterranean fever is
      relatively uncommon, and rarely described in the literature. Although headache
      occurs frequently, meningitis and convulsions are rare. We describe the case of a
      30-year-old man with attacks of meningitis. After colchicine therapy, no further
      recurrence of fever and meningitis were observed. These findings suggest that
      meningitis should be considered as an unusual manifestation of familial
      Mediterranean fever.

PMID- 15875626
TI  - Syphilitic scrotal abscess: the great mimic returns.
AB  - We present an unusual case of a scrotal abscess. The patient's previous history
      of syphilis highlights the need for a thorough sexual history especially in light
      of the current increasing incidence of syphilis in the UK.

PMID- 15875627
TI  - Incidental primary hyperparathyroidism in a hypercalcaemic woman with tuberculous
      peritonitis.
AB  - We report on a 51-year-old woman with initial hypercalcaemia and unknown ascites.
      In spite of unyielding laparoscopy, laparotomy showed findings compatible with
      tuberculous peritonitis (TBP). Unexpectedly, a series of examinations eventually
      revealed the concurrence of hyperparathyroidism due to a parathyroid adenoma.
      Anti-tuberculous regimen was given and was uneventful. However, hypercalcaemia
      was not decreased but sustained at a high level even after anti-tuberculous
      therapy for 3 months. Parathyroidectomy was performed with subsequent
      normalisation of hypercalcaemia. The aetiology of hypercalcaemia in a patient
      with an explored disease able to cause this electrolyte abnormality such as TBP
      may be a coexistent occult parathyroid adenoma.

PMID- 15875628
TI  - Primary brucellar psoas abscess: presentation of a rare case of psoas abscess
      caused by Brucella melitensis without any osteoarticular involvement.
AB  - The psoas abscess is an entity, sometimes forgotten in our daily practice,
      because of infrequency and difficulties in diagnosis. Primary psoas abscess is
      very rare and gram-positive micro-organisms account for more than 80% of the
      cases. Our case, a 62-year-old man was admitted with a 5-year history of back
      pain and fever. Physical examination was normal, except a palpable hepatomegaly
      with a mild tenderness over his lower right abdominal quadrant. The Brucella
      agglutination test was strongly positive with a titre of 1/640, as Rose Bengal
      Spot test. Blood cultures for brucella were positive on the fourth day and became
      negative, as the specific therapy started. Further examination with
      ultrasonography and computed tomography revealed an abscess of 40 + 75 mm in the
      psoas muscle. Complete resolution of symptoms achieved within 6 weeks. Although
      clinical presentation of psoas abscesses is often similar and non-specific, early
      aetiological diagnosis is extremely important, because of high achievement with
      appropriate antibiotic regimens. Brucellar psoas abscess seems very rare even in
      Turkey, where Brucella is still highly endemic. Such a case has not been
      previously reported from Turkey, as far as we know.

PMID- 15875629
TI  - Giant simple renal cyst complicated with hypertension.
AB  - Solitary renal cysts are a common and usually asymptomatic occurrence in older
      patients. They may be associated with hypertension or abdominal disturbances, as
      they can be responsible for compression of surrounding tissues and distortion of
      renal vessels. This report presents an interesting case of a hypertensive patient
      with a solitary renal cyst of a marked size. Owing to the high risk of performing
      a surgical procedure in such a patient, a distinct therapeutic solution was opted
      for. Successful management of this case was achieved by a combination of
      percutaneous fluid aspiration and injection of alcohol and Vibramycin inside the
      cystic cavity. Percutaneous fluid evacuation combined with the administration of
      a sclerosing agent is suggested as a safe and effective alternative for cyst
      decompression and blood pressure normalisation.

PMID- 15875630
TI  - Low-molecular-weight heparin successfully treating a nephrotic patient
      complicated by renal and ovarian vein thrombosis and pulmonary embolism.
AB  - Thromboembolic complications, frequently associated with idiopathic membranous
      glomerulonephritis, are frequent and serious problems associated with nephrotic
      syndrome. However, ovarian vein thrombosis associated with nephrotic syndrome has
      never been reported. This study describes the case of a 35-year-old woman with
      idiopathic membranous glomerulonephritis who developed left renal vein thrombosis
      with ovarian vein thrombosis and pulmonary embolism. The thromboembolic
      complications were successfully treated with low-molecular-weight heparin. Low
      molecular-weight heparin thus appears safe and effective for treating
      thromboembolism in nephrotic patients.

PMID- 15875631
TI  - Cortical dysplasia associating with abnormal vasculature complicated with
      subdural haemorrhage.
AB  - Cortical dysplasia is a neuronal migration disorder occasionally associated with
      anomalous draining veins. However, to our knowledge, no intracranial haemorrhage
      in conjunction with this association has been reported in the literature. We
      herein report a 7-month-old baby girl with cortical dysplasia associated with an
      ipsilateral cortical draining vein and complicated with subdural haemorrhage,
      with the diagnosis made by computed tomography and magnetic resonance imaging.
      This case demonstrated that patients with this condition could have an excellent
      prognosis even when the anomalous veins coexist with intracranial haemorrhage. We
      postulate that venous rupture may be the cause of this condition and further
      discuss the possible pathophysiology.

PMID- 15875632
TI  - Cyproterone acetate and ethinylestradiol-induced pill oesophagitis: a case
      report.
AB  - Although there are many cases of oesophagitis related to pill in medical
      literature, there are only a few reports concerning oesophagitis related to oral
      contraceptives, and none about cyproterone acetate and ethinylestradiol
      combination (Diane-35). In this report, we describe a female patient who suffered
      from odynophagia and retrosternal pain after taking Diane-35 for hirsutism. The
      endoscopic examination revealed two well-demarcated circumferential ulcers of 1
      cm diameter surrounded by relatively normal mucosa in mid-oesophagus. The patient
      had gone to bed immediately after taking the pill. Oral intake was stopped, and
      intravenous fluids and omeprazole were administered as part of treatment. The
      patient benefited from this approach very quickly and was discharged from
      hospital in 5 days. The oesophagus was completely normal in control endoscopy
      after 2 months. Diane-35 should be added to the list of drugs causing pill
      oesophagitis, and physicians should inform the patients that the pills should be
      taken with enough water and they should not lie down right after ingesting the
      pills.

PMID- 15875633
TI  - Acute fatty liver of pregnancy complicated with disseminated intravascular
      coagulation and haemorrhage: a case report.
AB  - Acute fatty liver of pregnancy (AFLP) is a rare disorder of unknown aetiology
      that is diagnosed typically in the third trimester or early postpartum period.
      The incidence is estimated to be 1/6692-1/13,328. The obstetric team must have a
      high index of suspicion of this pathology, particularly in the presence of
      clinical and laboratory findings, such as nausea, vomiting, jaundice, increased
      serum transaminase levels, increased prothrombin time and hypoglycaemia. Early
      diagnosis followed by prompt delivery and supportive care provides significantly
      improved maternal and perinatal outcome. Delay in diagnosis of this obstetric
      emergency may lead to rapid progression to hepatic failure, disseminated
      intravascular coagulation (DIC), haemorrhage, encephalopathy, multiple organ
      failure and finally death. The case of a 34-year-old woman, gravida 3, para 2,
      with AFLP complicated with DIC is presented herein with a review of literature
      and discussion of its origin.

PMID- 15875634
TI  - Misplaced Macroplastique injection presenting as a vaginal nodule and a bladder
      mass.
AB  - We describe a very unusual presentation of misplaced Macroplastique injection.
      This incidentally showed up as bladder lesion and vaginal nodule during a tension
      free vaginal tape surgery.

PMID- 15875635
TI  - Transvaginal contraception--avoid the bladder.
AB  - We report two cases of female contraceptive methods, resulting in urological
      presentation, with bladder foreign bodies. History, mode of diagnosis and
      surgical extraction technique differed in both patients. The first, where a
      thermometer was lost intravesically whilst measuring an internal temperature,
      presented immediately. A plain abdominal X-ray confirmed the position of the
      foreign body. Extraction was performed cystoscopically with the thermometer
      intact. A second patient, with recurrent urinary tract infections, was found to
      have an intrauterine contraceptive device (IUCD) in her bladder on ultrasound.
      Attempts to remove it endoscopically failed, and an, open procedure was required
      to free the IUCD from the bladder sidewall.

PMID- 15875636
TI  - Recurrent gastric adenocarcinoma presenting as acute appendicitis: a case report.
AB  - We report a case of acute appendicitis due to recurrent metastatic gastric
      adenocarcinoma involving only appendix, without the evidence of abdominal
      carcinomatosis 2 years after initial diagnosis of the primary gastric lesion.
      This case, in contrast to other previously reported cases that carried a dismal
      prognosis, had survived without tumour recurrent for more than 1 year after
      appendectomy, while this report was made.

PMID- 15875637
TI  - Colonic metastasis from squamous carcinoma of the lung: report of a case and
      review of the literature.
AB  - We describe a rare case with metastatic involvement of the gastrointestinal tract
      (colonic metastasis) secondary to lung cancer. After diagnostic work-up, a left
      hemicolectomy was performed. Patient has been alive and healthy 9 months after
      operation. We report the first case with the longest survival period after the
      diagnosis of metastasis, although the symptomatic gastrointestinal metastases
      from lung cancer generally follow a poor prognosis because of their advanced
      state and multiplicity.

PMID- 15875638
TI  - Primary T-lymphoma of the breast with bilateral involvement, unusual
      presentation.
AB  - Primary or secondary involvement of the breast is a rare form of extranodal
      lymphoma. Most reported primary non-Hodgkin lymphomas of the breast have a B-cell
      phenotype, those of T-cell phenotype are even more rare. Bilateral breast
      involvement at diagnosis also is very rare. We herein report a young female
      patient with bilateral breast involvement by low-grade T-cell malignant lymphoma.

PMID- 15875639
TI  - Chemotherapy for mediastinal germ cell tumor before definitive pathologic
      diagnosis.

PMID- 15875640
TI  - Solitary hepatic lymphangioma--a case report.
AB  - Hepatic lymphangioma is an extremely rare benign neoplasm that is usually
      associated with lymphangiomas of other viscera. We report a patient with huge,
      solitary hepatic lymphangioma involving only the liver. The clinical features and
      computed tomography findings of this case are described.

PMID- 15875641
TI  - Spontaneous rupture of hepatocellular carcinoma: a case report and review of
      literature.
AB  - Hepatocellular carcinoma (HCC) has a tendency for fatal spontaneous rupture
      leading to massive haemorrhage. A 64-year-old man presented with sudden, severe
      epigastric pain for 6 h. Systolic blood pressure was 80/50 mmHg, and pulse rate
      was 100/min. The patient's history did not reveal any operation or disease up to
      date. Contrast enhancement-axial computed tomography (CT) scan showed a tumoral
      lesion with a necrotic centre measuring 6 x 5 cm within 6th segment of the liver
      and a fluid collection (haemoperitoneum) at the periphery of the liver. At
      exploratory laparotomy, the liver was found to be cirrhotic, and an actively
      bleeding tumour confirmed in 6th segment of the liver. The tumour was resected.
      Post-operative recovery was unremarkable, and the patient was discharged on the
      14th post-operative day. Ruptured HCC should be included in the differential
      diagnosis of non-traumatic intra-abdominal haemorrhage.

PMID- 15875642
TI  - 'Metachronous' adenocarcinoma of the small intestine.
AB  - Adenocarcinoma of the small intestine accounts for less than 1% of primary
      gastrointestinal malignancies (1). Small intestine contains 75% of the length of
      the gastrointestinal tract with 90% of the surface mucosal area, and yet
      carcinoma is rare. Symptoms of small bowel adenocarcinoma are vague and non
      specific, and this region is relatively inaccessible which together contributes
      to their late diagnosis and poor prognosis. The authors report a case of two
      primary adenocarcinomas of the small intestine in the same patient.

PMID- 15875643
TI  - Atelectasis of the right medial basal segment mimicking primary lung cancer in an
      asthmatic patient.
AB  - A segmental collapse due to mucous plug in the bronchus tree may mimic malignant
      pathological conditions. We present a case of 58-year-old asthmatic patient with
      an obstruction of right medial basal bronchus due to mucous plug, which was
      simulating mediastinal mass. To the best knowledge, a similar case is not
      reported in the English medical literature.

PMID- 15875645
TI  - Groin abscess: a vesico-cutaneous fistula to the groin. A rare complication of
      open prostatectomy.
AB  - In developed countries, open prostatectomy for benign disease is now reserved for
      large prostates. This is not the case in the developing world where Millin's
      prostatectomy continues to be an important procedure, perhaps due to lack of
      endoscopic technology and training. We report a case of vesico-cutaneous fistula
      as a late complication of open prostatectomy presenting as a groin mass. A review
      of the English language literature shows this to be the first case of its kind.

PMID- 15875644
TI  - Misinterpretation of radioisotope imaging in pelvic kidneys.
AB  - We report the case of a gentleman referred with apparent worsening function in a
      hydronephrotic left-sided pelvic kidney. Imaging with Tc-99m
      Mercaptoacetyltriglycine (MAG 3) in 1999, showed that the left kidney contributed
      46% of renal function with no evidence of obstruction. Three years later, repeat
      scanning showed ectopic kidney function had decreased to 20% and with worsening
      pain, nephrectomy had been suggested. Review of the second MAG 3 scan revealed
      that only posterior images had been obtained. With pelvic kidneys, the pelvis
      forms a barrier between the radioactively labelled tracer and the gamma camera,
      thus, reducing the amount of radiation detected and underestimating function. A
      subsequent Dimercaptosuccinic acid scan (DMSA) was carried out with posterior and
      anterior images, the latter showing split renal function was identical to that
      seen on the initial scan. In patients with pelvic kidneys, anterior views must be
      obtained during radionuclide scanning if unnecessary nephrectomy is to be
      avoided.

PMID- 15875646
TI  - Laparoscopic ureteroneocystostomy for benign lower ureteric stricture: case study
      and literature review.
AB  - The surgical treatment of distal ureteric strictures depends on their length and
      aetiology. Laparoscopic procedures in this setting are uncommon. We describe a
      laparoscopic non-refluxing ureteroneocystostomy for a symptomatic distal ureteric
      stricture performed on a 26-year-old man. The operation was carried out
      successfully without complication. Blood loss was 100 ml with an operating time
      of 250 min. He was discharged on the fourth day and returned to work after 11
      days. Retrograde ureterography and cystography after 1 month showed no evidence
      of obstruction or reflux. At 3 months, an intravenous urogram showed excellent
      drainage and at 6 months the patient remained asymptomatic. We advocate the use
      of laparoscopic ureteroneocystostomy for benign distal ureteric stricture
      refractory to endoscopic procedures. In symptomatic patients, it is a feasible,
      safe, minimally invasive procedure with all the added benefits of laparoscopy
      compared with open repair. A non-refluxing anastomosis is preferable.
      Reconstructive and intracorporeal suturing skills are needed to carry out this
      procedure.

PMID- 15875647
TI  - Prostate abscess presenting as priapism.
AB  - Abscesses of the prostate are infrequently encountered now as a result of
      effective antibiotics. The clinical diagnosis remains difficult. Herein we report
      an unusual case of a prostate abscess presenting as priapism. The diagnosis and
      management of the case is discussed, and the literature is reviewed.

PMID- 15875648
TI  - Septic arthritis due to Aeromonas hydrophila: case report and review of the
      literature.
AB  - Aeromonas hydrophila is a rare human pathogen, and worldwide, soft tissue
      infections following water-related injuries are the most common. However, septic
      arthritis due to A. hydrophila remains uncommon with only seven cases previously
      reported in the English literature. In this report, we describe the important
      clinical features, microbiological findings and management of severe septic
      arthritis of the knee due to A. hydrophila in a healthy 13-year-old girl
      following an injury sustained in a private fresh water lake. A review of seven
      previously reported cases of septic arthritis due to A. hydrophila and the
      present case suggests that the infection commonly affected the knee and the meta
      /intercarpal-phalangeal joint and was frequently rapidly progressive following
      trauma in fresh water and or associated with leukaemia. Second and third
      generation cephalosporins, gentamicin, trimethoprim, ciprofloxacin and
      appropriate orthopaedic management should be promptly instituted. After chemical
      treatment and chlorination, fresh water becomes free of coliforms, but A.
      hydrophila persists more compared with the other strains of aeromonas, namely A.
      sobria and A. caviae. Seawater injuries, unlike freshwater injuries, are not
      usually associated with aeromonas infections. Further workup on the mechanisms of
      A. hydrophila resistance to chlorination could probably yield useful information
      in achieving new procedures of preventing and controlling such infections in
      public and private fresh water recreational facilities.

PMID- 15875649
TI  - An unusual cause of lower back pain: uterus didelphys and unilateral cervical
      atresia.
AB  - Backache among adolescents and young women is an unusual presenting feature to
      the Accident and Emergency Department as well as orthopaedic clinics. Here, we
      present a challenging case of a mullerian duct abnormality, which collectively
      has an incidence of 0.0001% of the population, and how its consideration and
      investigation will ensure optimum management in both acute and long-term.

PMID- 15875650
TI  - Sudden sensorineural hearing loss following intracarotid injection of heroin.
AB  - A 26-year-old male presented with sudden right-sided sensorineural hearing loss
      after injection of heroin into the right neck. The hearing loss was found to be
      profound with no other associated abnormalities on examination or investigation.
      There was no change at 3-month follow-up. This was most probably due to arterial
      injection and is a previously unreported complication of heroin abuse.

PMID- 15875651
TI  - Torsion of an omental lipoma presenting as an emergency.
AB  - Primary omental pathology is rare. A case of torsion of an omental lipoma is
      reported in a 77-year-old women presenting as an emergency with lower abdominal
      pain. Abdominal and pelvic CT scan was of value in the pre-operative
      investigation.

PMID- 15875652
TI  - Subungual exostosis following toe nail removal--case report.
AB  - Removal of toe nail is a minor procedure that can be under ring block with no
      significant complications. We report the case of a young lady who developed a
      rapidly growing subungual exostosis on her right great toe following nail
      removal. Inadvertent iatrogenic injury to the nail bed and underlying phalangeal
      periosteum during nail removal might have triggered off rapid bone growth
      resulting in the large exostosis. To our knowledge, this aetiology for subungual
      exostosis formation has not been reported before.

PMID- 15875654
TI  - Marburg virus disease, Angola.

PMID- 15875653
TI  - Avian influenza--Viet Nam and Cambodia--update.

PMID- 15875655
TI  - Global leprosy situation, 2004.

PMID- 15875656
TI  - GB virus C infection: is there a clinical relevance for patients infected with
      the human immunodeficiency virus?
AB  - In a search for new hepatitis viruses, two independent groups identified viruses
      named GB virus C and Hepatitis G Virus, which turned out to be different strains
      of the same agent. Despite its initial ascription to hepatitis viruses, this new
      virus does not cause any hepatitis. Thus, the term GB virus C is preferred. Soon
      after its discovery, a significantly better clinical course of HIV infection was
      demonstrated for patients coinfected with the GB virus C in 1998. These results
      were confirmed in other further studies, but not in all of them. Importantly,
      studies not confirming a positive influence usually found a neutral effect. The
      data for most of the studies had been mainly collected in the time prior to the
      availability of highly effective antiretroviral therapy (HAART). Since HAART has
      become available, some authors have reported a beneficial effect while others
      have shown only a neutral influence of GB virus C on HIV, considering either
      survival or the degree of response to HAART. An explanation for these
      discrepancies may be that different GB virus C strains exhibit different
      replication capacities. Understanding the mechanisms by how GB virus C and HIV
      interact may help find new strategies to fight HIV infection. Some recent in
      vitro findings have added evidence on how GB virus C might interact with and
      inhibit HIV replication. In this review, we update the current knowledge on GB
      virus C, its role in HIV infection in the HAART era, and discuss the potential
      mechanisms of its beneficial effect.

PMID- 15875657
TI  - Management of Kaposi's sarcoma in resource-limited settings in the era of HAART.
AB  - The introduction of highly active antiretroviral therapy (HAART) has changed the
      natural history of AIDS-associated Kaposi's sarcoma (KS). Although the use of
      HAART remains limited in low-resource settings, there are global initiatives to
      make these drugs available to several millions of HIV-infected persons. While
      there are multiple reports of KS regression during HAART with or without
      chemotherapy, there is little documentation on KS management in resource-limited
      settings. In this paper we review current KS treatments available worldwide and
      discuss the implications of the increased access to antiretrovirals for KS
      treatment strategies in resource-limited settings.

PMID- 15875658
TI  - Does RNA interference have a future as a treatment for HIV-1 induced disease?
AB  - RNA interference has recently emerged as an effective way to block the expression
      of specific messenger RNAs in eukaryotic cells. Using this approach, it has
      proven possible to block the replication of HIV-1 in cultured cells using small
      interfering RNAs targeted to viral sequences or to host messenger RNAs that
      encode factors critical for virus replication, such as the CCR-5 coreceptor.
      Unfortunately, the high sequence specificity of RNA interference, combined with
      the known tendency of HIV-1 to rapidly generate sequence variability, means that
      HIV-1 variants resistant to individual small interfering RNAs targeted to the
      viral genome arise rapidly. However, this problem may be circumvented by
      simultaneously targeting several essential HIV-1 sequences using RNA
      interference, or by targeting host genes that are essential for virus
      replication. Thus, RNA interference-based approaches have the potential to prove
      useful as novel treatments for HIV-1 induced disease, although the problem of how
      to efficiently deliver small interfering RNA expression vectors, or the small
      interfering RNAs themselves, to cells susceptible to HIV-1 infection in vivo,
      remains to be resolved.

PMID- 15875659
TI  - HIV-1 integration: an interplay between HIV-1 integrase, cellular and viral
      proteins.
AB  - To achieve a productive infection, the reverse transcribed cDNA of the human
      immunodeficiency virus type 1 (HIV-1) has to be inserted in the host cell genome.
      The main protein required to accomplish this reaction is the virally encoded
      integrase. In vitro, the recombinant integrase is capable of catalyzing the two
      subsequent reactions of the integration process, namely the 3' processing
      followed by the strand transfer, without other viral and/or cellular proteins.
      However, a number of studies indicate that the in vivo integration process also
      involves cellular proteins, assisting the virus to integrate in the cellular
      genome. These cellular proteins can play a role during different steps of the
      integration process, including nuclear import, integrase catalysis, integration
      site selection and DNA gap repair. In this review we summarize the candidate
      cellular proteins involved in the HIV-1 integration process identified so far and
      discuss their potential roles during HIV-1 replication.

PMID- 15875660
TI  - Hematopoietic stem cell-based gene therapy against HIV infection: promises and
      caveats.
AB  - Stem cell-based gene therapy of HIV infection aims at inhibiting HIV replication
      and the progression to AIDS by the introduction of antiviral genes in primitive
      hematopoietic stem cells (HSC). Ideally, after differentiation into mature blood
      cells, these antiviral genes should create a host-cell population that is
      resistant to HIV infection. Although the current gene therapy clinical trials
      established the safety and provided proof-of-principle for gene therapy of HIV-1
      infection, the overall results have been disappointing, and many issues still
      remain to be resolved before this approach can be efficiently used against HIV
      infection. Since a significant percentage of the stem cells in the patient have
      to be transduced to obtain a significant impact on HIV replication, the first
      prerequisite for successful gene therapy of HIV-1 infection consists of
      increasing the amount of transduced HSCs. Further improvements in gene transfer
      and gene therapy strategies will probably lead to future clinical successes. On
      the other hand, HIV-1 infection is a very complex disease, affecting various
      organs in addition to the T-cells, with an impact on T-cell homeostasis that is
      currently not fully understood. Even at low viral loads and before the advent of
      clinical symptoms, a high turnover of CD4+ cells exists in HIV-infected patients
      with functional implications for the homeostasis of the thymus, bone marrow and T
      cell homeostasis which may hamper the CD34+ HSC approach. Hence, the extent to
      which these alterations hamper a gene therapy approach, or can be reversed upon
      HAART, will determine the feasibility of future gene therapy against AIDS.

PMID- 15875661
TI  - Kaposi's sarcoma in the era of HAART-an update on mechanisms, diagnostics and
      treatment.
AB  - Kaposi's Sarcoma (KS) signified the AIDS epidemic in the 1980's and led to the
      discovery of the eighth human herpesvirus, KS-associated herpesvirus (KSHV), as
      the causative agent for this disease. Today we know a lot about KSHV and can
      begin to understand, diagnose and treat KS as a viral disease rather than another
      sarcoma.

PMID- 15875662
TI  - Mechanism of anti-apoptotic action of dipfluzine on neuronal damage of the rat
      hippocampal CA1 region subjected to transient forebrain ischemia.
AB  - AIM: To explore the relations between anti-apoptotic role of dipfluzine (DIP) and
      the death signaling transduction pathway initiated by CD95 molecules, and the
      transcription factor involved in the transcription regulation of CD95 molecules
      in the hippocampal CA1 region after transient forebrain ischemia. METHODS: The
      rat forebrain transient ischemia model was established through 15 min ischemia
      followed by 3 days reperfusion by using the four-vessel method. The rats were
      divided randomly into five groups: sham control group, ischemia/reperfusion (I/R)
      group, DIP treated groups (20, 40 and 80 mg x kg(-1) body weight, ig,
      separately). Western blotting and RT-PCR were performed to detect the expression
      changes of Fas, FasL, caspase 10 p20, caspase 8, I-kappaB-alpha, and p-I-kappaB
      alpha molecules in protein and mRNA levels, separately, and immunohistochemistry
      for molecular localization of Fas and FasL in rat hippocampus. RESULTS: The
      expression of Fas, FasL, and caspase 10 p20 in protein and mRNA levels increased
      after I/R, which was inhibited significantly after treatment with 20 and 40 mg x
      kg(-1) of DIP (P < 0.01). In 80 mg x kg(-1) of DIP group, the expression of Fas
      and FasL protein was not significantly different from that of I/R group (P >
      0.05). The expression of caspase 8 and I-kappaB-alpha showed no significant
      differences in all groups (P > 0.05), and no gene expression was observed for p-I
      kappaB-alpha protein in the study. DIP significantly affected molecular
      distribution of Fas and FasL protein in CA1 subregion of hippocampus. CONCLUSION:
      DIP inhibits the death signaling transduction pathway initiated by CD95 molecules
      in rat hippocampal CA1 subregion, and NF-kappaB transcription factor may not be
      involved in the transcription regulation of CD95 molecules after transient
      forebrain ischemia.

PMID- 15875663
TI  - Effects of isoliensinine on proliferation of porcine coronary arterial smooth
      muscle cells induced by phenylephrine.
AB  - AIM: To investigate the inhibitory effects and mechanism of action of
      isoliensinine (IL) on the proliferation of porcine coronary arterial smooth
      muscle cells (CASMCs) induced by phenylephrine (Phen) and its mechanisms of
      action. METHODS: MTT assay, immunohistochemical method and Western blotting were
      adopted. RESULTS: IL (0.03 - 3 micromol x L(-1)) could inhibit the CASMCs
      proliferation induced by Phen (0.1 micromol x L(-1)) in a concentration-dependent
      manner. IL (0.1 micromol x L(-1)) antagonized Phen-induced overexpression of PDGF
      beta and bFGF from 0.545 +/- 0.026 and 0.47 +/- 0.03 to 0.458 +/- 0.019 and 0.376
      +/- 0.017 (P < 0.01 , P < 0.01). IL (0.1 micromol x L(-1)) also decreased c-fos,
      c-myc and hsp70 overexpression induced by Phen from 0.57 +/- 0.04, 0.44 +/- 0.04
      and (173 +/- 36)% to 0.46 +/- 0.05, 0.372 +/- 0.021 and (115 +/- 35)%
      respectively (P < 0.01, P < 0.01, P < 0.01). CONCLUSION: IL exerted
      antiproliferative effect on CASMCs induced by phenylephrine, and its mechanisms
      were related to decrease the overexpression of growth factors (PDGF-beta, bFGF),
      protooncogene (c-fos, c-myc) and hsp70.

PMID- 15875664
TI  - [Metabolism of bicyclol in rat and human liver microsomes in vitro].
AB  - AIM: To study the drug metabolizing enzymes involved in the metabolism of
      bicyclol and identify the major metabolites of bicyclol in rat and human liver
      microsomes. METHODS: Bicyclol was incubated with rat and human liver microsomes.
      The metabolites of bicyclol were isolated by HPLC and identified by MS and 1H
      NMR. RESULTS: The metabolic rate of bicyclol in DEX-induced rat liver microsomes
      was obviously higher than that in untreated microsomes, while it was much lower
      in human liver microsomes. Ketoconazole was capable to exhibit strong inhibition
      ( >90%) on bicyclol metabolism. Two metabolites of bicyclol were identified to be
      4-hydroxy-4'-methoxy-6-hydroxy-methyl-6 '-methoxycarbonyl-2,3,2',3'-bis
      (methylene-dioxy) biphenyl and 4-methoxy-4'-hydroxy-6-hydroxymethyl-6'
      methoxycarbonyl-2,3,2',3'-bis (methylene-dioxy) biphenyl. CONCLUSION: CYP3A was
      considered as the major catalyst involved in bicyclol metabolism in vitro and two
      metabolites of bicyclol in rats were identified as 4-hydroxy-4'-methoxy-6-hydroxy
      methyl-6 '-methoxycarbonyl-2,3,2',3'-bis (methylene-dioxy) biphenyl and 4-methoxy
      4'-hydroxy-6-hydroxymethyl-6'-methoxycarbonyl-2,3,2',3'-bis (methylenedioxy)
      biphenyl.

PMID- 15875665
TI  - [Reversing effect of brassinolide on multidrug resistance of-CCRF-VCR1000 cells
      and a preliminary investigation on its mechanisms].
AB  - AIM: To investigate the effect of brassinolide, a plant growth modulator, on
      multidrug resistance (MDR) of human T lymphoblastoid cell line CCRF-VCR 1000
      which was obtained by progressively addition of vincristine (VCR) to sensitive
      CCRF-CEM cells, and to explore preliminarily the mechanism of reversing action.
      METHODS: MTT method was used to detect the resistant factor of resistant cell
      line and the reversing fold after addition of brassinolide. The intracellular
      accumulation of rhodamine 123, a fluorescent dye transported by P-glycoprotein
      was detected by flow cytometry, the catalytic activity of topoisomerase II was
      assessed by Sulliven method to find the effect of brassinolide on resistance. The
      protein expression of p53 was measured using Western blotting in the sensitive
      cells and resistant cells to explore the effect of brassinolide. RESULTS: The
      resistant factors of CCRF-VCR cells on adriamycin, VP-16 and VCR are respectively
      as 153.1, 55.9 and 8123.1 folds comparing to the sensitive cell line CCRF-CEM.
      After treatment of brassinolide under the concentration of 0.001 - 10.0 microg x
      mL(-1), the resistance of CCRF-VCR was reversed partly with the reversing folds
      respectively as 4.4 - 11.6. The intracellular accumulation of rhodamine 123 was
      significantly reduced in the resistant cells. After treatment of brassinolide,
      the accumulation increased, the level of fluorescent dye was situated between
      resistant cells and sensitive cells. No alteration of the catalytic activity of
      topoisomerase II was found among three groups. The level of protein expression of
      p53 in resistant cells was higher than that of sensitive cells. After
      brassinolide treatment, the expression of p53 in CCRF-VCR cells restored to the
      level of sensitive cells. CONCLUSION: Brassinolide could effectively reverse the
      resistance of CCRF-VCR cells by inhibiting the effusion of drug transported by P
      glucoprotein. To down regulate the abnormal expression of p53 maybe one of the
      mechanisms of reversing MDR for brassinolide.

PMID- 15875666
TI  - [Effects of oxyphenamone on myocardial ischemia in cats and rats].
AB  - AIM: To study the therapeutic effects of oxyphenamone, a novel inodilator, on
      myocardial ischemia. METHODS: The cardiac hemodynamic variables in cats with
      acute myocardial infarction induced by occlusion of the left anterior descending
      coronary artery (LAD) were recorded with a physiological polygraph and
      electromagnetic flowmeter. A model of myocardial necrosis induced by subcutaneous
      injection of isoproterenol was used for evaluating the effects of drugs on
      myocardial enzymes and morphological change. RESULTS: Intravenous injection of
      oxyphenamone (2 - 8 mg x kg(-1)) dose-dependently decreased heart rate, mean
      arterial pressure, vascular resistance and the parameters of myocardial oxygen
      consumption (tension time index, TTI) in cats with myocardial infarction. It
      increased myocardial contractile force and cardiac output transiently but showed
      no influence on the left ventricular pressure and cardiac work. The changes of
      myocardial morphology, creatine phosphate kinase (CPK), malodialdehyde (MDA) and
      serum glutamic-oxaloacetic transaminase (GOT) induced by isoproterenol in rats
      were diminished by intraperitoneal injection of oxyphenamone (4 - 8 mg x kg(-1)).
      CONCLUSION: By the examination of the cardiac hemodynamics, myocardial enzymes
      and morphology, it showed that the myocardial damage induced by ischemia or beta
      agonist can be antagonized markedly by oxyphenamone, indicating that oxyphenamone
      may be beneficial for the treatment of myocardial infarction.

PMID- 15875667
TI  - [Immunopharmacological action of sinomenine, an alkaloid isolated from Sinomenium
      acutum, and its mechanism of action in treating rheumatoid arthritis].
AB  - AIM: To observe the effects of sinomenine on the immune functions and apoptosis
      of murine lymphocyte as well as on human synovial fibroblast proliferation.
      METHODS: Both in vivo and in vitro tests were adopted. The lymphocyte
      proliferation induced by mitogens was assayed by MTT method. Spleen T lymphocyte
      subtypes were tested with flow cytometry. Spleen lymphocyte apoptosis was
      analyzed by flow cytometry and DNA ladder methods. In vitro test was adopted to
      observe the effects of sinomenine on the proliferation of human fibroblast of
      rheumatoid arthritis. RESULTS: Sinomenine can inhibit the proliferation of mouse
      lymphocytes induced by ConA, LPS and anti-CD3 mAb but not PMA in vitro, and
      inhibit the proliferation induced by LPS and PMA in vivo. Sinomenine can reduce
      up-regulated CD4+/CD8+ ratio of T lymphocyte subtype in adjuvant arthritis rat.
      At the same concentration increased apoptosis ratio. As to human synovial
      fibroblast, sinomenine can significantly inhibit proliferation of human
      fibroblast. CONCLUSION: Sinomenine can inhibit the immunological function and
      correct imbalance of CD4+/CD8+ ratio of T lymphocyte subtype. It can also
      increase apoptosis ratio of spleen lymphocyte. This may be the mechanism of its
      immunological inhibitory effect.

PMID- 15875668
TI  - [Synthesis and antibacterial activity of ciprofloxacin derivatives].
AB  - AIM: To study the synthesis and antibacterial activity of ciprofloxacin
      derivatives. METHODS: Ciprofloxacin derivatives were synthesized primarily from 2
      methyl-5-nitroimidazol and ciprofloxacin through nucleophilic substitution. The
      antibacterial activity of the synthesized compounds were tested. RESULTS: Nine
      new compounds were synthesized. The structure of the title compounds were
      confirmed by 1H NMR, MS and element analysis. CONCLUSION: Compounds II, IVC and
      IVD showed appreciable antibacterial activity, and were worth further studying.

PMID- 15875669
TI  - [Design, synthesis and insulin-sensitizing activity of some peroxisome
      proliferator-activated gamma agonists].
AB  - AIM: To find new peroxisome proliferator-activated y agonists with high activity
      and low toxicity. METHODS: Based on JTT-501 and JTT-20993, new isoxazolidine-3,5
      dione and noncyclic 1,3-dicarbonyl compounds were designed and synthesized. Their
      insulin-sensitizing activities were evaluated. RESULTS: Eight new compounds were
      obtained. The structures of synthesized compounds were characterized by NMR, MS
      and IR. Four compounds (1A-4A) showed insulin-sensitizing activities. CONCLUSION:
      Compounds (1A and 3A) showed excellent insulin-sensitizing activities and should
      be worth further investigation.

PMID- 15875670
TI  - [New dimeric phthalide derivative from Angelica sinensis].
AB  - AIM: To study the chemical constituents of the roots of Angelica sinensis.
      METHODS: Silica gel column chromatography was used to separate the chemical
      constituents. Their structures were elucidated by chemical and spectral analysis
      (IR, MS, 1D and 2D NMR, etc.). RESULTS: Besides three known phthalide
      derivatives, one new dimeric phthalide derivative and a pair of epimer were
      isolated and their structures were identified as Z-3',8',3'a,7'a-tetrahydro
      6,3',7,7'a-diligustilide-8'-one (1), Z,Z'-6,6',7,3'a-diligustilide (2) and the 8
      epimer (3) of 2 on the basis of spectral data. CONCLUSION: Compound 1 is a new
      dimeric phthalide derivative, and compound 3 was first reported from radix
      Angelica

PMID- 15875671
TI  - [Steroidal constituents from Dioscorea parviflora].
AB  - AIM: To study the chemical constituents of Dioscorea parviflora. METHODS: The
      chemical constituents were isolated by silica gel and RP-18 column
      chromatography, and their chemical structures were elucidated by IR, NMR and MS.
      RESULTS: Eleven steroides have been isolated from EtOH extract of Dioscorea
      parviflora and identified as isonarthogenin 3-O-alpha-L-rhamnopyranosyl-(1-->2)
      beta-D-glucopyranoside (I), diosgenin-diglucoside (II), prosapogenin A of dioscin
      (III), dioscin (IV), deltonin (V), deltoside (VI), methyl deltoside (VII),
      diosgenin 3-O-beta-D-glucopyranosyl (1-->3)-beta-D-glucopyranosyl-(1-->4)-[alpha
      L-rhamnopyranosyl-(1-->2)]-beta-D-glucopyranoside (VIII), parvifloside (IX),
      methyl parvifloside (X), diosgenin (XI), and a mixture of beta-sitosterol and
      stigmasterol. CONCLUSION: Compound X is a new compound. Compounds VII and X were
      methyl ethers of VI and IX, respectively, and may be produced during isolation.
      Compound I is isolated from Dioscorea L., and II, IV from Dioscorea parviflora
      for the first time.

PMID- 15875672
TI  - The chemical constituents of Rhododendron ovatum Planch.
AB  - AIM: To study the chemical constituents of Rhododendron ovatum Planch. METHODS:
      The chemical constituents were isolated and purified by silica gel column
      chromatography and identified on the basis of their physiochemical and spectral
      data. RESULTS: Seven compounds were isolated and identified. Their structures
      were established as 3,5,7-trihydroxylchromone 3-O-beta-D-xylopyranoside (I),
      taraxerol (II), beta-sitosterol (III), betulinic acid (IV), quercetin (V),
      quercetin-3-O-alpha-L-rhamnopyranoside (VI), and D-glucose (VII). CONCLUSION:
      Compound I is a new compound. Compounds II-VII were isolated from this plant for
      the first time.

PMID- 15875673
TI  - [Chemical constituents from the seeds of Annona squamosa].
AB  - AIM: To study the antitumor active constituents of the seeds from Annona squamosa
      L. (Annonaceae). METHODS: Various chromatographic techniques were used to isolate
      and purify the constituents. Their physico-chemical properties and spectral data
      were determined to elucidate the structures. RESULTS: Eleven compounds were
      isolated and identified as annonaceous acetogenins: squamocenin (1), annotemoyin
      2 (2), reticulatain-2 (3), squamocin-I (4), squamocin-B (5), squamocin (6),
      motrilin (7), squamostatin-D (8), squamostatin-E (9), cherimolin-1 (10),
      cherimolin-2 (11) from the ethyl alcohol extract of A. squamosa L. CONCLUSION:
      Squamocenin (1) is a new acetogenin. Annotemoyin-2 (2) and reticulatain-2 (3)
      were isolated from this plant for the first time.

PMID- 15875674
TI  - [Detection of the metabolites of dehydroepiandrosterone in urine with gas
      chromatography-combustion-isotope ratio mass spectrometry].
AB  - AIM: To establish a method to determine the isotope ratios of 13C to 12C of
      dehydroepiandrosterone and its metabolites in urine, for detecting the source of
      dehydroepiandrosterone or its metabolites. METHODS: Preliminary separation of
      endogenous anabolic androgenic steroids could be achieved using solid phase
      extraction, enzymolysis and thin layer chromatography. The source of
      dehydroepiandrosterone and other endogenous anabolic androgenic steroids could be
      detected by their delta values with gas chromat ography-combustion-isotope ratio
      mass spectrometry. RESULTS: The 5 values of some metabolites of
      dehydroepiandrosterone reduced after the administration of dehydroepiandrosterone
      preparation. In these cases the data indicated that exogenous anabolic androgenic
      steroids were administrated. CONCLUSION: The source of dehydroepiandrosterone or
      its metabolites in urine could be detected by measuring their delta values with
      this method.

PMID- 15875675
TI  - Pharmacokinetics of mangiferin in rat plasma after oral administration of a
      single dose of suanzaoren decoction.
AB  - AIM: To study the pharmacokinetics of mangiferin in rats after oral
      administration of a single dose of Suanzaoren decoction. METHODS: An HPLC method
      was established using puerain as internal standard. Plasma samples were
      deproteinized with acetonitrile-acetic acid (9:1), followed by evaporation of the
      acetonitrile to dryness. The resultant residue was then dissolved in mobile phase
      and HPLC separation was achieved on a Hypersil C18 (200 mm x 4.6 mm ID, 5 microm)
      column at room temperature. The mobile phase consisted of acetonitrile-water
      (12:88) with 1% acetic acid and 1% tetrahydrofuran at a flow rate of 0.7 mL x
      min(-1). The UV detection wavelength was set at 320 nm. RESULTS: The calibration
      curve was shown to be linear over the range from 0.536 to 26.8 microg x mL(-1)
      (r2 > or = 0.995). Mean recovery was determined as 92.7%. Within-day and between
      day precisions were less than 9. 1% RSD. The limit of quantitation (LOQ) was
      0.536 microg x mL(-1). The maximum plasma concentration (Cmax), the time to reach
      peak concentration (Tmax) and the apparent elimination half-life (T1/2) were
      (10.5 +/- 2.2) microg x mL(-1), (5.8 +/- 0.4) h and (5.0 +/- 0.3) h,
      respectively. CONCLUSION: The validated HPLC method developed has been applied to
      take a limited view of pharmacokinetics profile of mangiferin in rat plasma after
      having orally taken a single dose of Suanzaoren decoction.

PMID- 15875676
TI  - [Metabolic pathways of dipfluzine in rats].
AB  - AIM: To investigate the metabolic pathways of dipfluzine in rats. METHODS: After
      an oral dose of dipfluzine (80 mg x kg(-1)) to rats, urine was collected for 12
      h. The metabolites of dipfluzine in urine were chromatographed and identified by
      LC/DAD/MS methods. RESULTS: In the rat urine, there were 1-(4-fluorophenyl)-4
      piperazinylbutanone and its glucuronide, 4-hydroxybenzophenone and its
      glucuronide, 4-fluoro-gamma-hydroxybenzenebutanoic acid and its glucuronide and
      sulfate, diphenylmethanol and its glucuronide, dipfluzine, and benzophenone.
      CONCLUSION: In rats, dipfluzine was mainly metabolized in the pathways of N
      desalkylation at 1- and 4-positions of piperazine ring. Some of metabolites were
      further conjugated with glucuronic acid and/or sulfuric acid.

PMID- 15875678
TI  - Effect of iontophoresis on skin permeation of defibrase.
AB  - AIM: To investigate the effect of iontophoresis on skin permeation of defibrase.
      METHODS: Iontophoresis was carried out in side-by-side chambers, excised rat skin
      membrane (RSM) or human epidermis membrane (HEM). The effects of electrode
      polarity, permeation medium pH and ionic strength were evaluated. RESULTS:
      Permeation of defibrase caused by anodal iontophoresis was more effective [the
      apparent permeability coefficient was (1.2 +/- 0.4) x 10(-4) cm x h(-1)] than
      that of cathodal iontophoresis [(4.3 +/- 1.4) x 10(-5) cm x h(-1)]. The amount of
      permeated defibrase caused by anodal iontophoresis in pH 7.4 medium was (25 +/-
      5) x 10(-14) mol x cm(-2), which was higher than that of in pH 6. 4 permeation
      medium [(15 +/- 4) x 10(-14) mol x cm(-2)]. CONCLUSION: Iontophoresis could
      enhance skin permeation of defibrase. Electroosmotic flow effect played an
      important role.

PMID- 15875677
TI  - [Pharmacokinetics and distribution of superoxide dismutase liposomes in rats].
AB  - AIM: To evaluate the effects of surfactants on the pharmacokinetics and
      distribution in rats after intravenous administration of SOD liposomes. METHODS:
      The liposomes were prepared by reverse phase evaporation method. The activity of
      SOD was assayed by method of xanthine oxidase. RESULTS: The T1/2 of SOD solution,
      common SOD liposome, SOD liposomes modified by DSPE-PEG2000 and Tween 80 were
      0.25, 0.34, 0.66 and 0.41 h, respectively; AUC were 12.48, 24.66, 41.16 and 33.02
      microg x h x mL(-1), respectively. Compared with the common liposome, the
      liposomes modified by DSPE-PEG and Tween 80 decreased the content of SOD in liver
      and spleen, but increased in brain. CONCLUSION: The three kinds of liposomes
      could increase T1/2 and AUC in some extent, especially in PEG-L group. Tween-L
      could increase the SOD content in brain, and PEG-L could decrease the SOD content
      in the liver and spleen compared with the common liposome.

PMID- 15875679
TI  - [Preparation of alginate-chitosan-poly (lactic-co-glycolic acid) composite
      microsphere and its regulation of protein release].
AB  - AIM: To elevate the encapsulation efficiency, decrease the burst release and
      improve the release of protein entrapped in poly (lactic-co-glycolic acid) (PLGA)
      microspheres. The bovine serum albumin (BSA) composite microspheres of alginate
      chitosan-PLGA were prepared and the release characteristics of BSA from this
      composite microspheres were studied. METHODS: The much smaller calcium alginate
      microcapsules were first prepared by a modified emulsification method in an
      isopropyl alcohol-washed way and coated with chitosan, then the alginate-chitosan
      microcapsules were further entrapped in PLGA to form the composite microspheres.
      The protein concentration was determined using a BCA protein assay kit. The
      release profiles were changed with various formulation factors. RESULTS: The
      average diameter of the composite microcapsules was about 30 microm. Comparing
      with 60% to 70% of the conventional PLGA microspheres, the average encapsulation
      efficiency was more than 80%, and the burst releases in phosphate buffer solution
      of the composite microspheres decreased from 40% and 50% to 25% and further to 5%
      in saline solution. CONCLUSION: The novel composite microspheres were prepared,
      the drug encapsulation efficiency increased and the burst release decreased. The
      desired release profiles could be obtained by regulating the ratios of PLG and
      PLA in the composite microspheres.

PMID- 15875681
TI  - [High-frequency ultrasound (HFUS) and its biomedical applications].
AB  - HFUS is ultrasound whose frequency is higher than 10MHz. HFUS imaging features
      very high resolution, which is up to 20 microm. HFUS is used to check the
      superficial organs such as eye ball and skin with extremely high resolution. When
      applied to small animals, HFUS is able to scan the body and the embryo in
      microscopic scale. The blood flow information in microcirculation can be detected
      if the high frequency Doppler technology is applied. Convenience, simplicity,
      real time and high resolution of HFUS have lead to a significant role in
      biomedical research and clinical applications.

PMID- 15875680
TI  - [Preparation and characterization of indomethacin/poly(N-isopropylacrylamide)
      beta-cyclodextrin complex with temperature-sensitivity].
AB  - AIM: To synthesize poly(N-isopropylacrylamide)/cyclodextrin conjugate (PNIPA-beta
      CD) as thermosensitive drug carrier, incorporate indomethacin into the conjugate
      and evaluate the drug release from the carrier in vitro. METHODS: PNIPA-beta-CD
      was synthesized by introducing carboxyl terminated PNIPA into the primary hydroxy
      group of beta-CD. The obtained conjugate was characterized by FTIR, 1H NMR and
      DSC. The indomethacin/PNIPA-beta-CD complex was prepared by lyophilization. In
      vitro drug release from the complex was carried out at 25 degrees C and 37
      degrees C respectively. RESULTS: Thermosensitive PNIPA-beta-CD was synthesized
      successfully. The LCST is 35 degrees C, as measured by turbidity method. The drug
      release from indomethacin/PNIPA-beta-CD complex was slower at 37 degrees C than
      that at 25 degrees C. CONCLUSION: Thermosensitive PNIPA-beta-CD with molecular
      inclusion capacity is a potential carrier for drug sustained release.

PMID- 15875682
TI  - [Elemental research on intelligent non-invasive temporary pacemakers].
AB  - Some research on intelligent non-invasive temporary pacemakers is introduced in
      this paper. An industrial computer, some IC chips and other elements are used to
      construct its hardware, and its software is in C++ language. The experimental
      device has some intelligent functions of recognizing some arrhythmia. The system
      has a pacemaker module and an ECG monitor module. Its software includes a main
      program, a RS-232C communication program, a printer VxD, a pacing control VxD and
      ECG signal pretreatment and recognizing program and so on. The pacing-generating
      circuit is employed to make the precision control of pacing current. The
      communication between industrial-computer system and ECG module is completed
      through the DLL. The real time processing of ECG signals is based on filter
      method for a higher recognizing ratio. The system calculates several parameters
      to recognize certain arrhythmia and uses MIT/BIH database to validate the
      reliability of ECG recognition.

PMID- 15875683
TI  - [CT/PET image registration based on a region similarity measure].
AB  - In this paper, CT/PET multimodality medical image registration is performed by a
      region similarity measure (RSM), accompanied with an improved segment method and
      Powell optimization algorithm. RSM has been proved to be a quick, accurate and
      robust algorithm by the experimental results.

PMID- 15875684
TI  - [The establishment and evaluation of the subjective measuring instrument for
      tonic accommodation].
AB  - An instrument for subjective measurement of tonic accommodation has been
      established based on the Badal system and Scheiner principle. The results of
      tonic accommodation between subjective measurement and objective measurement have
      no significant difference. Its establishment is important for the measurement of
      accommodation parameter in the myopia research center.

PMID- 15875685
TI  - [Development of a portable ECG monitor with diagnostic & therapeutic functions
      and its clinical applications].
AB  - A portable ECG monitor is introduced in the paper, which has a temporary
      intravenous and transesophageal fixable rate pacing function. During the PSVT
      attack, the tachyarrythmia can be stopped by the transesophageal cardiac pacing
      while the ECG signals are monitored. The instrument has some advantages such as
      small size, low price and good practicality. It is worth while introducing and
      popularizing it to all hospitals.

PMID- 15875686
TI  - [The design of a transcranial magnetic stimulation (TMS) system and its
      implementation].
AB  - Transcranial magnetic stimulation (TMS) is a non-invasive diagnostic and
      therapeutic technigue. This paper expounds the design and manufacture of the TMS
      system, which meets all the requirements of the TMS study and clinical diagnosis
      and treatments.

PMID- 15875687
TI  - [Development and applications of an auto-analyzing system for Model TJ-IV vector
      cardiogram].
AB  - A new computer-assisted vector-cardiogram analyzing system Model TJ-IV developed
      based on Model TJ-III, has been using in the routine clinical work in order to
      evaluate its features and performances. The system employs a 586 computer with a
      CPU of 120 MHz, a special low-noise amplifier, a 12 bit A/D tranducer and the C
      language for programming. The examinations of 206 cases were performed and all
      the vector-cardiograms were analyzed by the computer system and by manipulative
      methods respectively. In comparison with the manipulative methods the system has
      a very high accuracy of picture-recognition. The accuracy for distinguishing the
      onsets and terminals of orthogonal ECG waves is 98% while that for distinguishing
      the peaks and troughs of the waves is 100%. These waves include P, Q, R, S, R'
      and S' waves. The new system is capable to provide the parameters of more than
      591 items, including 46 newly-developed diagnostic parameters. The testing and
      analyzing of 12 parameters of orthogonal ECG and plane VCG have proved that the
      results of the aboved two methods have no difference. The new system has a very
      high accuracy of picture-recognition and index calculation with many technical
      problems existing in the old versions, solved--a great improvement of safety and
      anti-interference and an increase of the detecting & diagnostic speed.

PMID- 15875688
TI  - [Research and development of a clinical laboratory information system].
AB  - A clinical laboratory information system consists of two parts--the information
      system and the management system. Its development is based on scientific and
      rational lab-workflow, consulting the international standard HL7 Protocol, and
      combined with barcode technique and instrument communication. The information
      system mainly manages the data which come from the whole lab testing process
      while the management system is dominating the lab office work and management
      decisions.

PMID- 15875689
TI  - [The design of an anti-rotation reduction internal fixator and its applications
      in spine fracture surgeries].
AB  - This article introduces a new-type anti-rotation reduction internal fixator,
      which can be applied in various spine fractures and dislocations in order to
      shorten the operation time, to raise reduction effect, and to reduce the
      complications such as the loss of reduction, broken nail, broken rod etc.
      Biomechanical tests and clinical applications have proved that the internal
      fixator has the features of a short operation time, a definite fixation and few
      complications.

PMID- 15875690
TI  - [A discussion over the safety of medical electrical systems].
AB  - This essay explains several essential concepts which are closely related to the
      safety of medical electrical systems. It expounds the key problems of building up
      medical electrical systems based on safety requirements, and performing
      compliance tests. Therefore,it is of realistic significance when carrying out
      GB9706.15.

PMID- 15875691
TI  - [Current research and development trend of swallowable biotelemetry systems].
AB  - Swallowable biotelemetry systems are one kind of implantable biotelemetry
      systems. The research about swallowable biotelemetry systems is rapidly growing
      recently because they can be used to measure physiological and pathological
      parameters of human gastrointestinal tracts in vivo and they significantly
      improve patient comfort. This paper presents the current research of swallowable
      biotelemetry systems domestically and abroad. The development trend of these
      systems is analyzed at the end of the paper.

PMID- 15875692
TI  - [A comparison between the eye trackers of laser cornea correction systems made by
      foreign manufacturers].
AB  - Photo refractive keratectomy (PRK) and laser Situ Keratomileusis (LASIK) have
      been used for over a decade and become popular in China. Principles and
      characteristics of eye trackers made by several famous foreign manufacturers are
      introduced in this paper and their developing direction in the future is pointed
      out too.

PMID- 15875693
TI  - [Adverse events of medical devices and the role of the government].
AB  - The concept of medical devices adverse events is introduced in the paper. The
      contents of surveillance of adverse events are discussed and the government's
      role in the surveillance is presented as well.

PMID- 15875694
TI  - [The new administration system for medical devices in Japan].

PMID- 15875695
TI  - [The dependability and safety of biomaterials and medical devices].
AB  - This article describes emphatically the dependability, safety and their guarantee
      measures for biomaterials and medical devices.

PMID- 15875696
TI  - [Some considerations about carrying out IEC 60601-2-2, Ed.3/1998 for high
      frequency surgical equipment].

PMID- 15875697
TI  - [The transducer's calibration of medical ventilators and discussion on relative
      technical concerns].
AB  - Based on the structure and principle of transducers for medical ventilators, this
      paper analyzes the causes of transducers' failures, and introduces some
      corresponding calibration methods. Besides, some suggestions about how to reduce
      different kind of transducer failures are put forward.

PMID- 15875698
TI  - [Reasonable applications of automatic exposure control in computed radiography].
AB  - This paper is to explore the reasonable applications of automatic exposure
      control in computed radiography, and to improve the quality of CR images. It is
      very important to select a suitable KV value in automatic exposure control in
      computed radiography. At the same time, a suitable ionization chamber, correct
      density compensation and necesary post-processing should be selected.

PMID- 15875699
TI  - [Development of the portable automatic pneumatic tourniquet].
AB  - This article introduces the basic structure, features and the priciples of a
      portable automatic pneumatic tourniquet and its prospects of applications.

PMID- 15875700
TI  - [A discussion about the network safety of the hospital information system].
AB  - This paper introduces the measures guaranteeing the network safety of the
      hospital information system.

PMID- 15875701
TI  - [A cost & benefit management system for investment equipments].
AB  - Being aimed at the management of investment equipments, the flow of data has been
      put forward and the two main modes of data calculating have been established by
      our relying on No.1 Network of Military Healthy. The real-time management has
      been realized by the system in regard to eguipments' contact, charges, payouts,
      interest, payment, forecast and decision-makiing. It has been steadily test
      running for more than 10 months in our hospital, and data have been processed
      exactly and creditably.

PMID- 15875702
TI  - [The situation and countermeasure of medical measurements].
AB  - This paper introduces the significance, the present development situation and
      some suggestions of the medical measurements.

PMID- 15875705
TI  - Generational approaches to current nursing issues. How younger and older nurses
      can coexist.

PMID- 15875708
TI  - Professional liability insurance: straight answers to your questions.

PMID- 15875706
TI  - Newly released study examines shortage of nursing faculty.

PMID- 15875709
TI  - Avian influenza, Cambodia--update.

PMID- 15875710
TI  - Marburg haemorrhagic fever, Angola--update.

PMID- 15875711
TI  - Marburg haemorrhagic fever--fact sheet.

PMID- 15875712
TI  - Plague.

PMID- 15875713
TI  - Degradation of xenobiotic compounds by lignin-degrading white-rot fungi:
      enzymology and mechanisms involved.
AB  - White-rot fungi (WRF) are ubiquitous in nature with their natural ability to
      compete and survive. WRF are the only organisms known to have the ability to
      degrade and mineralize recalcitrant plant polymer lignin. Their potential to
      degrade second most abundant carbon reserve material lignin on the earth make
      them important link in global carbon cycle. WRF degrade lignin by its unique
      ligninolytic enzymatic machinery including lignin peroxidase, manganese
      peroxidase, laccase, cellobiose dehydrogenase, H2O2-generating enzymes, etc. The
      ligninolytic enzymes system is non-specific, extracellular and free radical based
      that allows them to degrade structurally diverse range of xenobiotic compounds.
      Lignin peroxidase and manganese peroxidase carry out direct and indirect
      oxidation as well as reduction of xenobiotic compounds. Indirect reactions
      involved redox mediators such as veratryl alcohol and Mn2+. Reduction reactions
      are carried out by carboxyl, superoxide and semiquinone radicals, etc.
      Methylation is used as detoxification mechanism by WRF. Highly oxidized chemicals
      are reduced by transmembrane redox potential. Degradation of a number of
      environmental pollutants by ligninolytic system of white rot fungi is described
      in the present review.

PMID- 15875714
TI  - Role of topoisomerases in cytotoxicity induced by DNA ligand Hoechst-33342 and UV
      C in a glioma cell line.
AB  - DNA ligand Hoechst-33342 significantly enhances UV induced cytotoxicity in human
      glioma cell lines (BMG-1 & U-87) with supra additive increase in cell death,
      cytogenetic damage, cell cycle delay, apoptosis and inhibition of PLDR.
      Cytotoxicity of Hoechst-33342 arises due to its interference in the breakage
      rejoining reaction of DNA topoisomerases by stabilization of cleavable complexes.
      Since topoisomerases have also been implicated in the generation of potentially
      lethal DNA breaks by interaction with various types of DNA damage including UV
      induced DNA lesions, we investigated in present studies the role of functional
      topoisomerases in the synergistic cytotoxicity of Hoechst-33342 and UV in a human
      glioma cell line (BMG-1). Topoisomerase I activity analyzed by the plasmid
      relaxation assay, was significantly enhanced upon UV irradiation, implying a
      possible role of this enzyme in the processing of UV induced lesions. However,
      this increase in the activity was reduced by >50% in cells incubated with Hoechst
      33342 for 1 hr prior to irradiation. Imunoflowcytometric analysis of the
      chromatin bound topoisomerases I and II levels (cleavable complex) using
      topoisomerases I and II anti-antibodies showed a good correlation between the
      induction of apoptosis by Hoechst-33342 and UV and enhancement in the level of
      topoisomerase II mediated cleavable complexes. Induction of apoptosis was
      associated with a decline in the level of Bcl2. Taken together, these studies
      show that supra additive cytotoxic effects of UV-C and Hoechst-33342 in BMG-1
      cells are consequences of enhanced stabilization of topo II mediated cleavable
      complexes and alterations in specific signal transduction pathways of apoptosis,
      besides the inhibition of topoisomerase mediated repair processes.

PMID- 15875715
TI  - Sodium nitroprusside relaxes goat coronary artery through activation of calcium
      dependent K+ channels.
AB  - In the present investigation we have examined the hypothesis that calcium
      dependent K+ channels (K(Ca)) are involved in the sodium nitroprusside (SNP)
      induced vasodilatation of goat coronary artery. SNP (10(-9)-3 x 10(-6) M), added
      cumulatively, relaxed K+ (30 mM)-contracted coronary artery ring segments in a
      concentration-dependent manner with an EC50 of 1.32 x 10(-7) M (95% CL, 0.93-1.86
      x 10(-7) M; n = 21). K(Ca) blocker, tetraethyl ammonium (1 mM) caused a rightward
      shift in the concentration-response curve of SNP with a corresponding increase in
      EC50 (1.62 x 10(-6) M; 95% CL, 0.44-6.02 x 10(-6) M, n = 4) of nitro vasodilator.
      Lowering of extra cellular Ca2+ in the physiological saline solution to 1/4 of
      normal selectively attenuated the vasorelaxant response of SNP, thereby causing
      an increase in its EC50 (2.4 x 10(-6) M; 95% CL, 1.23-4.68 x 10(-6) M, n = 4).
      Exposure of the tissues to high K+ (80 mM) solution, a protocol adopted to reduce
      the K+ gradient across the cell membrane, markedly inhibited the coronary artery
      relaxations induced by SNP (EC50, 2.54 x 10(-6) M; 95% CL, 1.31-4.91 x 10(-6) M,
      n = 4), when compared with tissues contracted with low K+ (30 mM) solution (EC50
      7.9 x 10(-8); 95% CL, 4.4 x 10(-8)-1.44 x 10(-7) M, n = 6). The results suggested
      that a major component of SNP-induced relaxation of goat coronary artery was
      mediated by K(Ca) channels.

PMID- 15875716
TI  - Midgut antibodies reduce the reproductive capacity of Anopheles stephensi
      (Diptera: Culicidae).
AB  - Rabbits immunized with polypeptides of midgut of glucose fed A. stephensi
      resulted in high titer of antibodies (10(4)-10(6)) as detected by ELISA. Effect
      of antisera on fecundity, hatchability and engorgement was investigated.
      Fecundity was reduced drastically (62.4%). Eight polypeptides were recognized by
      the antisera raised against midgut tissues viz., 92, 85, 55, 52, 45, 38, 29 and
      13 kDa. Cross reactivity of these antibodies with different tissues of A.
      stephensi as well as different species of Anopheles was also analyzed. The
      results indicated that anti-mosquito midgut antibodies had the potential to
      disrupt the reproductive physiology of mosquitoes in view of the present study,
      there is a need for further investigation with target antigens.

PMID- 15875717
TI  - Evidence for presence of female produced pheromone components in male scent brush
      extract of castor semi-looper moth Achaea janata L.
AB  - Hexane extract of male terminalia (along with scent brushes) of castor semi
      looper moth, Achaea janata L, elicited significant olfactory responses in both
      male and female insects by electroantennogram recording technique. However, male
      extract in the wind tunnel evoked noticeable behaviour responses in the female
      insects only. Orientation response of the males to the male extract was not
      evident in wind tunnel experiments. Two electrophysiologically-active compounds
      were identified from the male extract. Based on GC retention times and mass
      spectrometry the two compounds were confirmed as (Z,Z)-9,12-octadecadienal and
      (Z,Z,Z)-3,6,9-heneicosatriene. These two compounds are also constituents of
      female produced four-component blend of A. janata.

PMID- 15875718
TI  - Production of heptaene antifungal antibiotic by Streptomyces purpeofuscus CM
      1261.
AB  - A strain of Streptomyces purpeofuscus CM 1261 isolated from a sample of compost
      collected locally was found to possess strong antagonistic activity against 4
      human pathogenic fungi i.e., Candida albicans, Aspergillus niger, Microsporum
      gypseum and Trichophyton sp. The active antifungal compound produced by it was
      found to be a heptaene group of polyene antifungal antibiotic.

PMID- 15875719
TI  - Potential antifilarial activity of fruit extracts of Ficus racemosa Linn. against
      Setaria cervi in vitro.
AB  - Effect of alcoholic and aqueous extracts of the fruits of F. racemosa Linn., on
      the spontaneous movements of both the whole worm and nerve muscle preparation of
      Setaria cervi and on the survival of microfilariae in vitro was studied.
      Alcoholic as well as aqueous extracts caused inhibition of spontaneous motility
      of whole worm and nerve muscle preparation of Setaria cervi characterized by
      increase in amplitude and tone of contractions. Initial stimulatory effect was
      not observed with aqueous extract on whole worm preparation, while effect of
      alcoholic extract on whole worm and nerve muscle preparation was characterized by
      an increase in amplitude and tone of contractions followed by paralysis. The
      concentrations required to inhibit the movement of the whole worm and nerve
      muscle preparation for alcoholic extract of fruits of F. racemosa were 250 and 50
      microg/ml, respectively, whereas aqueous extract caused inhibition of the whole
      worm and nerve muscle preparation at 350 and 150 microg/ml, respectively,
      suggesting a cuticular barrier. Both alcoholic and aqueous extracts caused death
      of microfilariae in vitro. LC50 and LC90 were 21 and 35 ng/ml, respectively for
      alcoholic, which were 27 and 42 ng/ml for aqueous extracts.

PMID- 15875720
TI  - Antihepatotoxic effect of beta-carotene on paracetamol induced hepatic damage in
      rats.
AB  - Enzyme levels of serum glutamate oxaloacetate transaminase (SGOT), serum
      glutamate pyruvate transaminase (SGPT) and alkaline phosphatase (ALP) increased
      following paracetamol induction were significantly lowered due to pretreatment
      with the beta-carotene (BC). This supplementation reversed the trend inducing a
      significant decrease in bilirubin and urea levels. Paracetamol administration
      significantly reduced hepatic glycogen, glutathione (GSH), glutathione-S
      transferase (GST), glutathione peroxidase (GPX) and glutathione reductase (GSH
      R). Pretreatment of rats with BC significantly increased the enzyme activities.
      The results suggest hepatoprotective activity of BC.

PMID- 15875721
TI  - Renoprotective effect of grape seeds extract in ethylene glycol induced
      nephrotoxic mice.
AB  - Grape seed extract treatment in ethylene glycol (EG) induced nephrotoxic mice
      improved antioxidant status and significantly decreased urinary lactate
      dehydrogenase (LDH) and lipid peroxidation. The extract rendered antioxidant
      protection against oxidative stress induced by EG and may help in protecting
      renal tissue against EG toxicity.

PMID- 15875722
TI  - Regulation of trehalose metabolism by Adox and AdoMet in Saccharomyces
      cerevisiae.
AB  - Effect of a potent methylation inhibitor oxidized adenosine (Adox), and a
      universal methyl group donor S-adenosyl-L-methionine (AdoMet) on trehalose
      metabolism was studied in two haploids of S. cerevisiae of mating types MATalpha,
      met3 (6460 -8D) and MATa, leu2, ura3, his4 (8534 -10A). Trehalose level decreased
      in presence of Adox in both strains. Both neutral trehalase (NT) and trehalose-6
      phosphate (tre-6-p) synthase activities increased in presence of Adox in -8D
      strain. Decrease in trehalose level in -8D thus could not be explained in the
      light of increased tre-6-p synthase activity; however, it could be correlated
      with increased NT activity. In strain -10A, NT activity was reduced in presence
      of Adox while tre-6-p synthase activity increased. Enzyme activity profiles in 
      10A thus do not explain the reduced trehalose level on Adox treatment. Effect of
      AdoMet was not very prominent in either strain, though in -8D a small increase in
      trehalose level was seen on treatment. Intracellular AdoMet level of untreated
      cells of -10A was seen to be almost six times higher than that of -8D. Further,
      AdoMet treatment caused increase in its level compared to untreated cells,
      suggesting AdoMet uptake. No effect of either compound was seen on acid trehalase
      (AT) activity in any strain. The results suggest that there was a possible effect
      of demethylation on trehalose metabolism (particularly in the synthetic
      direction) in both strains, though effect of methylation was not very prominent,
      the reason for which is not very clear.

PMID- 15875723
TI  - Isolation and characterization of a green tissue-specific promoter from pigeonpea
      [Cajanus cajan (L.) Millsp.].
AB  - Expression of rbcS genes encoding small subunit of rubisco, most abundant protein
      in green tissue, is regulated by at least three parameters--tissue type, light
      conditions and stage of development. One of the green tissue-specific promoters
      of rbcS gene family was isolated from pigeonpea by PCR. Expression of uidA gene
      encoding beta-glucuronidase in the transgenic tobacco plants under the control of
      pigeonpea rbcS promoter, clearly showed that this promoter was as strong as pea
      rbcS3A promoter characterized earlier. Study of the sequence similarity with pea
      rbcS3A promoter, especially the region (boxes I and III) that is required for
      rbcS3A expression, showed more than 50% divergence. In contrast, pigeonpea
      promoter sequence isolated in the present study was more similar to that of
      spinach and rice rbcS promoters.

PMID- 15875724
TI  - In vitro studies of Bacopa monnieri--an important medicinal plant with reference
      to its biochemical variations.
AB  - Micropropagation of Bacopa monnieri was achieved on MS and B5 medium supplemented
      with BAP and NAA using leaf explants and nodal segments. Best results were found
      on MS medium in both the explants with BAP (2.0 mg/l) showing higher percentage
      of regeneration. Besides that the biochemical parameters, like chlorophyll,
      carbohydrate, protein, of leaves both in vivo and in vitro have also been carried
      out in order to establish the sustainability of plants.

PMID- 15875725
TI  - Regeneration of plantlets from in vitro raised leaf explants of Cleisostoma
      racimeferum Lindl.
AB  - Protocorm like bodies (PLBs), callus and shoot buds developed in culture from in
      vitro raised foliar explants of Cleisostoma racimeferum. Among the different
      basal media, better result was obtained on MS medium containing sucrose (3%) and
      BA (2 microM) with approximately 80% frequency after 40 days of culture. Young
      leaves (15 week old) produced better PLBs. Whole leaf placed vertically upside-up
      orientation can regenerate PLBs and shoot buds (80%). PLBs and shoot buds formed
      on entire surface of the leaves. Cultures on BA and NAA (2 and 2 microM
      respectively in combination) stimulated callus mediated regeneration (68%). The
      rooted plantlets regenerated within 8-10 week from PLBs and shoot buds on MS
      medium containing IAA and kinetin (2 microM each in combination). BA containing
      medium triggered multiple shoot bud formation, while NAA alone or in combination
      with other growth regulators was inhibitory. Incorporation of activated charcoal
      (0.01%) in the medium stimulated formation of repetitive PLBs and multiple shoot
      buds. Rooted plants were ready for harvest after 20-22 week of initiation of
      culture. About 65% of the potted plants survived after 3 months in the poly
      house.

PMID- 15875726
TI  - Comparative evaluation of whole blood D-dimer test to plasma D-dimer test for
      diagnosis of disseminated intravascular coagulation.
AB  - Three rapid D-dimer test methods were compared for the diagnosis of acute
      disseminated intravascular coagulation (DIC). These were (a) SimpliRED, an
      autologous red cell agglutination assay. (b) DIMERTEST latex agglutination assay,
      containing monoclonal antibody DD-3B6/22(6), and (c) D-DI latex agglutination
      assay containing mouse anti-human D-dimer monoclonal antibodies. The D-DI latex
      method having higher sensitivity (100%) and specificity (81%) in clinically acute
      DIC was postulated as the gold standard and compared with the other two methods.
      The results suggest that D-DI latex agglutination assay containing mouse anti
      human D-Dimer monoclonal antibodies are the better assay methods amongst all the
      three kits analyzed. It is advisable to look for the nature of the antibody used
      to coat the latex particles in plasma based kits. In emergency setting RBC kits
      may be of some use as rapid diagnosis is advantageous.

PMID- 15875727
TI  - Strategies for laboratory cost containment and for pathologist shortage:
      centralised pathology laboratories with microwave-stimulated histoprocessing and
      telepathology.
AB  - The imposition of laboratory cost containment, often from external forces,
      dictates the necessity to develop strategies to meet laboratory cost savings. In
      addition, the national and worldwide shortage of anatomical pathologists makes it
      imperative to examine our current practice and laboratory set-ups. Some of the
      strategies employed in other areas of pathology and laboratory medicine include
      improvements in staff productivity and the adoption of technological developments
      that reduce manual intervention. However, such opportunities in anatomical
      pathology are few and far between. Centralisation has been an effective approach
      in bringing economies of scale, the adoption of 'best practices' and the
      consolidation of pathologists, but this has not been possible in anatomical
      pathology because conventional histoprocessing takes a minimum of 14 hours and
      clinical turnaround time requirements necessitate that the laboratory and
      pathologist be in proximity and on site. While centralisation of laboratories for
      clinical chemistry, haematology and even microbiology has been successful in
      Australia and other countries, the essential requirements for anatomical
      pathology laboratories are different. In addition to efficient synchronised
      courier networks, a method of ultra-rapid tissue processing and some expedient
      system of returning the prepared tissue sections to the remote laboratory are
      essential to maintain the turnaround times mandatory for optimal clinical
      management. The advent of microwave-stimulated tissue processing that can be
      completed in 30-60 minutes and the immediate availability of compressed digital
      images of entire tissue sections via telepathology completes the final components
      of the equation necessary for making centralised anatomical pathology
      laboratories a reality.

PMID- 15875729
TI  - Smooth muscle in the female pelvic peritoneum: a clinicopathological analysis of
      31 women.
AB  - AIM: To study the presence and morphological features of smooth muscle in the
      subcoelomic mesenchyme with the aim of establishing both a normal range for the
      female pelvis, and its possible relationship to endometriosis, diffuse peritoneal
      leiomyomatosis (LPD) and other forms of 'mullerianosis'. METHODS: Seventy
      laparoscopically obtained pelvic peritoneal biopsies accessioned over a 16-month
      period were examined from 31 women clinically suspected of endometriosis. These
      biopsies were selected for the presence of assessable, appropriately oriented
      peritoneum, sufficiently distant from focal endometriosis to allow a presumption
      of 'normality'. The histological features and morphometric measurements of smooth
      muscle in these biopsies were documented. Pathological changes, where present,
      were recorded. RESULTS: Focal endometriosis was identified in 28 (40%) of the
      biopsies, nine (12.9%) displayed other manifestations of 'mullerianosis', 11
      (15.7%) showed focal chronic inflammation or fibrosis only, and 22 (31.4%)
      displayed no specific pathological changes. Of 70 biopsies, 52 contained smooth
      muscle within the subcoelomic mesenchyme, directly below the peritoneal
      mesothelium. Biopsies in which smooth muscle was identified were predominantly
      from the region of the uterosacral ligaments (16/18) and pelvic side wall
      (22/25). The biopsies without a smooth muscle layer were predominantly from the
      pararectal area (7/8) or the rectal serosa (2/4). Where present, smooth muscle
      varied in prominence, depth, thickness of the layer and organisation of muscle
      bundles. Patterns ranged from thin, widely spaced and wispy fibres to a more or
      less continuous band of either horizontally and/or vertically organised fibres.
      Both focal and diffuse arrangements were evident. 'Neovascularisation' was
      observed laparoscopically in some areas that corresponded with prominent smooth
      muscle development. CONCLUSIONS: Smooth muscle occurs sufficiently frequently
      immediately beneath the peritoneum of the female pelvis, and with a sufficiently
      predictable anatomical distribution, to be regarded as a normal component of the
      microanatomy of this tissue in the patients studied.

PMID- 15875728
TI  - Genetic aberrance of sporadic MEN 2A component tumours: analysis of RET.
AB  - AIM: The molecular pathogenesis of familial multiple endocrine neoplasia (MEN)
      type 2 (parathyroid adenoma with medullary thyroid carcinoma and adrenal
      pheochromocytoma) is associated with a germ-line mutation in the RET proto
      oncogene. We undertook this study to clarify the relationship between the
      tumorigenesis of apparently sporadic MEN type 2 component endocrine tumours and
      RET mutations. METHODS: Direct sequencing for RET exon 10, 11, 12, 13, 14, 15 and
      16 and immunohistochemistry for RET monoclonal antibody were performed on the
      archival tissues of 84 cases of sporadic endocrine tumours, including 22
      medullary thyroid carcinomas (MTCs), 35 adrenal pheochromocytomas (APCs), 18
      paragangliomas (PGs), and nine parathyroid adenomas (PTAs). RESULTS: PCR-based
      direct sequencing revealed somatic point missense mutation within 22.7% of exon
      13 of the RET proto-oncogene (four cases of E768D, one case of S7781) in MTCs. No
      RET genotype and morphological association was observed in MTCs or APCs. APCs
      revealed significantly lower levels of immunoexpression of RET, even versus PGs.
      CONCLUSIONS: The genetic mutation in RET is relatively low in incidence, and
      likely to play an insignificant role in the molecular pathogenesis of sporadic
      MTC. The molecular bases of PG and APC seem to be different despite their
      embryological and histological similarities.

PMID- 15875730
TI  - Gastrointestinal stromal tumours (GISTs): a clinicopathological and molecular
      study of 66 cases.
AB  - AIMS: Predicting the clinical behaviour of gastrointestinal stromal tumours
      (GISTs) is difficult and criteria delineating benign from malignant cases are not
      firmly established. The aims of this study were to define the clinicopathological
      and molecular features of 66 GISTs, and to determine whether any specific
      parameters were associated with patient outcome. METHODS: Archival cases of GIST
      from two major teaching hospitals in Western Australia were studied. Inclusion
      criteria for the study were: (1) appropriate morphology, (2) CD117 positivity,
      (3) adequacy of pathological material for study, and (4) exclusion of other
      tumour types on the basis of immunophenotypic and/or ultrastructural features.
      Expression of CD117, CD34, S100 protein, keratin (using broad spectrum MNF116),
      alpha-smooth muscle actin (SMA) was determined by immunohistochemistry. PCR and
      single strand conformation polymorphism (PCR-SSCP) analysis were used to screen
      for mutations in exons 11 and 9 of c-kit. RESULTS: There were equal numbers of
      males and females with a mean age at diagnosis of 60 years, followed up for a
      mean of 54 months. Thirteen patients (21%) had died of GIST by the end of the
      study. Tumours were mostly located in the stomach (67%) and small intestine (SI;
      25%). The cell types were pure spindle (68%), pure epithelioid (12%) and mixed
      epithelioid/spindle (20%). c-kit mutations were found in 69% of GISTs, with the
      large majority (91%) occurring in exon 11. Size > or = 10 cm, tumour necrosis and
      pure epithelioid cell morphology each were the only factors significantly
      associated with adverse survival (p=0.038, and p=0.047 and p=0.028,
      respectively). Mitotic activity > or = 5/50 HPF showed a definite trend
      association with adverse survival, but unlike some other studies, did not achieve
      statistical significance (p=0.067). c-kit mutations were more frequent in small
      intestinal GISTs (p=0.05) and in those with pure spindle cell morphology
      (p=0.023) but were not associated with patient outcome. CONCLUSION: In this
      study, size > or = 10cm, necrosis and/or pure epithelioid cell morphology
      correlated significantly with adverse survival. Mitotic activity showed a strong
      association with survival but this did not reach statistical significance. c-kit
      mutations occurred mainly in GISTs of the SI, and in purely spindle cell tumours.
      While the mutation status did not associate with patient outcome in this series,
      this remains a controversial issue, and further studies are needed to assess
      whether the type of mutation affects response to tyrosine kinase inhibitor
      therapy in metastatic GISTs. CD117 staining of any mesenchymal lesion of the
      gastrointestinal tract should be mandatory for accurate classification. PCR-SSCP
      analysis is a fast, sensitive and relatively inexpensive method of analysing c
      kit mutations, which may be important prognostically and also of therapeutic
      relevance in the assessment of new tyrosine kinase inhibitor therapies.

PMID- 15875731
TI  - Characteristic localisation of denatured high-density lipoprotein (HDL) at the
      periphery of a lipid core in human atherosclerotic lesions.
AB  - AIMS: High-density lipoprotein (HDL) has been reported to efflux cholesterol
      (Chl) from the cell membrane, and the physiological balance between the influx
      and efflux of Chl is important in the formation of atherosclerotic lesions.
      METHODS: In order to clarify these mechanisms in atherosclerotic lesions, the
      ratios of areas of apoprotein A-I (apo A-I)-positive areas were determined using
      a fluorescence polarisation microscope coupled to a spectrometer. RESULTS:
      According to the staining patterns of apo A-I, atherosclerotic lesions are
      classified into three types, namely, focal dense area (FA), diffuse dense area
      (DA) and shading area (SA). In FA, protein was prominent and lipid was minimal in
      the intercellular space of degenerated cells in the thickened intima. In DA, the
      protein and lipid were co-localised. In SA, at the periphery of lipid core, more
      lipids were present than protein. In the developed lesions, FA and SA were
      statistically bigger than those in the early lesions. CONCLUSIONS: These results
      suggest that an effective micro-solubilisation mechanism in FA may result in a
      low lipid content. Moreover, accumulated HDL may alter the relationship between
      various lipid vesicles and crystals in the extracellular matrix, and be an
      additional factor for the fragility of atheromatous plaques at the periphery of
      the lipid core.

PMID- 15875732
TI  - p53 alterations in sequential biopsies of Asian follicular lymphoma: a study of
      immunohistochemical staining pattern and gene mutations by PCR-SSCP in paraffin
      embedded tissues.
AB  - AIM: Tumour suppressor gene p53 is a common target in carcinogenesis, reported to
      be altered and functionally inactive in 70% of human cancers. Although p53
      mutations are less commonly present in haematological malignancies when compared
      with other solid tumours, they have been reported in histological transformation
      of follicular lymphoma. We aimed to investigate the frequency of p53 gene
      alterations in paraffin-embedded tissue using commercially available PCR-SSCP,
      and to correlate the results with P53 protein expression by immunohistochemistry.
      METHODS: Surgical samples from seven patients with a total of 17 sequential
      biopsies were retrieved for the study of p53 gene expression using
      immunohistochemical stain, and gene status by PCR-SSCP for exons 5-8. The tumours
      were graded according to the WHO classification criteria. P53 was distinctly over
      expressed in five transformed higher grade biopsies, and all except one showed
      electrophoretic mobility shift in PCR-SSCP analysis. Sequencing analysis revealed
      single nucleotide substitutions in three of four of these high-grade transformed
      cases with band shift (75%), whereas some other studies reported a lower
      frequency of 25-30%, and mobility shift result was found to correlate with P53
      expression. Lower grade tumours without P53 over-expression did not demonstrate
      band shift, and sequencing analysis did not reveal mutations. CONCLUSIONS: We
      demonstrated the feasibility of adopting PCR-SSCP for screening of p53 mutations
      in archival tissue samples in this study, and there is a strong correlation of
      p53 gene over-expression and mutation events in high-grade transformed tumours.

PMID- 15875733
TI  - Correlations of cell cycle regulators (p53, p21, pRb and mdm2) and c-erbB-2 with
      biological markers of proliferation and overall survival in breast cancer.
AB  - AIM: The biological impact of cell cycle regulatory proteins on breast cancer
      progression is widely recognised, although mostly unclear. The aim of this
      preliminary study was to investigate the correlations of several cell cycle
      modulators (p53, p21, pRb, and mdm2) and c-erbB-2 expression with cell
      proliferation markers (S-phase fraction [SPF] and Ki-67) and overall survival in
      breast cancer. METHODS: The series comprised 50 women with stage I-II invasive
      ductal breast carcinoma (median follow-up 87 months), who were selected for their
      tumour proliferative characteristics (15 low, 15 high, and 20 intermediate
      proliferative tumours). Tumour differentiation was assessed following the
      Nottingham grading criteria. Cell cycle regulators, oestrogen receptor status,
      and Ki-67 index were analysed by immunohistochemistry on paraffin embedded
      material (cut-offs 10%). c-erbB-2 was evaluated according to a standardised
      immunohistochemical assay and borderline cases were confirmed by FISH analysis.
      Ploidy and SPF were determined by DNA flow cytometry on frozen samples. Chi
      square test and Fisher's exact test were applied to analyse the statistical
      significance of data. RESULTS: Positive immunostaining was observed in nine (18%)
      p53+, 30 (60%) p21+, 13 (26%) pRb+, and one (2%) mdm2+ cases. c-erbB-2 expression
      was considered positive in 11 (22%) cases. In the subset of patients dead of the
      disease, a high incidence of c-erbB-2 over-expression (7/10, 70%) was verified.
      In general, no significant correlations among cell cycle regulators or between
      the latter and histopathological or proliferative characteristics were found.
      Only the p53-/p21+ phenotype significantly correlated with low SPF (p=0.048), and
      p21 positivity showed a trend to be associated with low SPF (p=0.083). No
      statistically significant correlations between cell cycle inhibitors and clinical
      outcome were found. On the contrary, c-erbB-2 over-expression showed significant
      correlations with DNA aneuploidy (p<0.001), high SPF (p<0.001), high tumour
      grading (p=0.008), lack of oestrogen receptors (p=0.036), and poor overall
      survival (p<0.001). CONCLUSIONS: The results seem to indicate the lack of
      correlations of cell cycle regulatory proteins with cell proliferation markers
      and overall survival in breast cancer, in contrast to c-erbB-2 over-expression
      which was found to be associated with increased proliferation rate and worse
      prognosis.

PMID- 15875734
TI  - Specific biochemical markers of bone metabolism and cytokine study confirm the
      diagnosis of malignant infantile osteopetrosis at birth using cord blood sample.
AB  - AIMS: To investigate the serum creatine kinase isoenzyme pattern, specific
      biochemical markers of bone metabolism, and cytokines in a Chinese family with
      osteopetrosis, and correlate abnormalities with the pathophysiology of this
      condition. METHODS: A Chinese female baby was diagnosed with malignant infantile
      osteopetrosis at the age of 3 weeks by clinical history and biochemical
      investigations. We studied the laboratory and radiological manifestations of this
      index case and her family members. RESULTS: Serum CK-BB fraction of our index
      patient was elevated to 18.0% (normal 1.6-7.6%). Her biochemical markers of bone
      resorption including serum C-terminal telopeptide concentration and urine N
      terminal telopeptide to creatinine ratio were decreased to 0.54 microg/L (normal
      0.72-1.56 microg/L) and 159 x 10(-6) (normal 372-900 x 10(-6)), respectively.
      Serum cytokines including soluble receptor activator of nuclear factor kappa-B
      ligand (sRANKL) concentration was suppressed to 0.11 pmol/L (normal 0.23-0.82
      pmol/L) and osteoprotegerin (OPG) concentration was 4.9 pmol/L (normal 2.8-4.9
      pmol/L), resulting in an elevated OPG to sRANKL ratio of 44.5 (normal 3.8-19.4)
      in favour of bone formation. CONCLUSIONS: If left untreated, this condition is
      usually fatal within the first year of life. With early diagnosis, management
      including bone marrow transplantation can be planned ahead and will result in a
      better survival.

PMID- 15875735
TI  - Cytotoxic chemotherapy upregulates pro-apoptotic Bax and Bak in the small
      intestine of rats and humans.
AB  - AIMS: Small intestinal crypt cells rapidly undergo apoptosis in response to
      cytotoxic drug treatment that results in gastrointestinal toxicity. The Bcl-2
      family have been implicated in both positive and negative regulation of
      intestinal cell apoptosis. The aim of this study was to examine the effect of
      cytotoxic treatment on Bcl-2 protein expression in patients and rats with
      tumours. METHODS: Four pro- and four anti-apoptotic members of the Bcl-2 family,
      caspase-3 and p53 were examined in small intestinal crypts before and after
      treatment in rats and humans. Immunohistochemistry identified changes in protein
      expression over time, while relative RT-PCR was used to investigate mRNA
      expression in rat small intestine. RESULTS: Cytotoxic treatment increased p53 and
      caspase-3 which coincided with elevated levels of apoptosis. Bax and Bak protein
      and mRNA expression also significantly increased at 6 hours following treatment
      in rats. Bax and Bak protein increased at day 1 after treatment in humans. Anti
      apoptotic Mcl-1 protein decreased within 24hours. Other Bcl-2 family members
      showed only modest changes. CONCLUSION: Increased expression of Bax and Bak but
      not other Bcl-2 family members is associated with apoptosis in small intestinal
      crypts and may amplify the sensitivity and susceptibility of crypt cells to
      chemotherapy-induced enteropathy.

PMID- 15875736
TI  - Detection of anti-dsDNA by ELISA using different sources of antigens.
AB  - AIM: To compare different sources of DNA for use in ELISA-based assays for anti
      dsDNA antibody detection in systemic lupus erythematosus (SLE) diagnosis. METHOD:
      Bacterial genomic DNA from Flavobacterium menignosepticum, Proteus vulgalis,
      Seratia marcescens, Streptococcus pyogenes and Salmonella typhimurium and genomic
      DNA from human blood were used as antigens for IgG anti-dsDNA detection by enzyme
      linked immunosorbent assay (ELISA). Eighty-six sera were tested, 28 derived from
      patients with SLE, 28 from patients with other rheumatic diseases and 30 from
      normal human subjects. RESULTS: Genomic DNA from Flavobacterium menignosepticum
      and human blood had high sensitivity (75%, 82%) and specificity (91%, 91%) for
      anti-dsDNA detection in diagnosis of SLE. However, human genomic DNA was the most
      effective antigen of all antigens studied. The assay had a higher sensitivity but
      lower specificity than commercial ELISA (61% sensitivity and 95% specificity).
      There was a high level of correlation between commercial ELISA and ELISA using
      human genomic DNA as antigen (r=0.776, p<0.001) and they exhibited a high level
      of diagnostic agreement with each other (kappa=0.890, p<0.001). CONCLUSION: The
      genomic DNA from human blood is a potentially useful source of antigen for the
      detection of anti-dsDNA by ELISA. However, further studies are required to
      compare the performance of ELISA using this source of antigen against commercial
      radioimmunoassays for anti-dsDNA detection.

PMID- 15875737
TI  - Discordant detection of Chlamydia pneumoniae in patients with carotid artery
      disease using polymerase chain reaction, immunofluorescence microscopy and
      serological methods.
AB  - AIM: To determine the presence of Chlamydia pneumoniae in carotid plaque and
      peripheral blood mononuclear cells (PBMCs) using a combination of serology,
      direct antigen detection by immunofluorescence (IF) microscopy and polymerase
      chain reaction (PCR), and to compare the results obtained from each assay.
      METHODS: A total of 54 atherosclerotic carotid plaques were tested for the
      presence of Chlamydia by PCR and IF methods. Of these 54 patients with carotid
      artery disease (CAD), 43 were also tested for the presence of C. pneumoniae DNA
      in PBMCs and for Chlamydia antibodies using two methods, the Medac Chlamydien
      rELISA and Focus Chlamydia microimmunofluorescence (MIF) methods. RESULTS:
      Eighteen of the 54 (33%) carotid specimens were positive for the presence of C.
      pneumoniae DNA, whereas only two of 43 (5%) patients had C. pneumoniae DNA
      present within their PBMC fraction. Chlamydial antibodies were detected by MIF
      and/or rELISA in 56% (24/43) of the patients tested. None of the 43 patients was
      C. pneumoniae positive in all of the test specimens (plaque, PBMCs and serum).
      CONCLUSIONS: Chlamydia pneumoniae is commonly found in Australian patients with
      CAD. Serology and PCR-based detection of C. pneumoniae in PBMCs and plaque give
      highly discordant results.

PMID- 15875738
TI  - Test and teach. Number fifty-three. Diagnosis: Spindle cell ductal carcinoma in
      situ with neuroendocrine differentiation.

PMID- 15875739
TI  - Myiasis by Chrysomya bezziana in surgical pathology.

PMID- 15875740
TI  - Bone marrow lymphoid aggregates simulating histological features of non-Hodgkin's
      lymphoma in Felty's syndrome.

PMID- 15875741
TI  - Fine needle aspiration cytology of dermatofibrosarcoma protuberans in the breast:
      a case report.

PMID- 15875742
TI  - Pentalogy of Cantrell with a double-outlet left ventricle.

PMID- 15875743
TI  - 'Myxopapillary' ependymal rest presenting as a pre-sacral skin tag.

PMID- 15875744
TI  - Multiple mucinous tumours.

PMID- 15875745
TI  - Primary intratesticular mucinous cystadenocarcinoma.

PMID- 15875746
TI  - [Palliative care, a prize of increasing conscience].

PMID- 15875747
TI  - [A region rich in professionals and in the supply of care].

PMID- 15875748
TI  - [A dynamic regional health scheme].

PMID- 15875749
TI  - [Domiciliary care: a multi-discipline system is on the march].

PMID- 15875750
TI  - Paying lip service to patient safety: better communication, improved work
      environment seen as lowering medical errors.
AB  - Recent studies and discussions are shining a new light on how better
      communication can lead to better patient outcomes, improved patient safety,
      improved morale, and reduced turnover, especially among nursing staffs. While it
      is a seemingly simple idea on the surface, the issue must surmount years of
      entrenched-and sometimes disrespectful-behavior that sometimes has caused
      patients to receive less-than-optimum clinical care.

PMID- 15875751
TI  - The pursuit and possibilities of evidence-based medicine.
AB  - Evidence-based medicine has been used to guide healthcare that works, but
      sometimes, the system delivers care that ends up too little, too much, or just
      wrong. Participants at a Washington, DC, forum looked recently at what can be
      done to make a smoother path to the most effective set of practices that improve
      healthcare quality.

PMID- 15875752
TI  - Courts continue to wrestle with ERISA preemption.

PMID- 15875753
TI  - Expansion of physician's information disclosure responsibility eyed by
      Massachusetts Court. Darke v. Estate of Dr. Jeffery M Isner.

PMID- 15875754
TI  - [Children and computers].

PMID- 15875755
TI  - [Therapy for soft tissue sacrcoma: more questions than answers?].

PMID- 15875756
TI  - Potential applications of breath isoprene as a biomarker in modern medicine: a
      concise overview.
AB  - Human breath contains hundreds of trace volatile organic compounds. These
      volatile substances may be generated in the body or may be absorbed as
      contaminants from the environment. Some of the endogenous substances are
      characteristic markers of pathophysiological processes and clinicians are already
      using breath testing of such substances as an additional non-invasive diagnostic
      tool for certain diseases. Isoprene, another volatile compound, is formed
      endogenously in humans, and while the biochemical pathways of biosynthesis and
      exact origins of isoprene found in human breath have not been elucidated in
      sufficient depth, its measurement in exhaled breath has been suggested as a non
      invasive indicator with diagnostic potential. This test has not yet reached the
      level of routine clinical methods and is still under development. Breath isoprene
      levels have been reported to be altered in a number of clinical conditions;
      however, the physiological meaning of these changes has not been established.
      Various lines of supportive evidence suggest that isoprene is related to
      cholesterol biosynthesis. Therefore, breath isoprene measurements could
      potentially be used for mass screening for lipid disorders and could, at minimum,
      serve as an additional parameter to complement invasive tests for monitoring the
      efficacy of lipid-lowering therapy, pharmacological and dietary or lifestyle. As
      a potentially useful biomarker of mevalonate synthesis in humans, it may have non
      invasive applications, not only in metabolic disorders, but possibly also in
      cancer screening. In the present work, we aim to give a concise overview of
      breath isoprene, its measurement techniques, problems concerning its
      physiological meaning, and potential applications as a non-invasive biomarker in
      modern medicine.

PMID- 15875757
TI  - Hypertensive retinopathy.

PMID- 15875758
TI  - [Excessive computer usage in adolescents--results of a psychometric evaluation].
AB  - Excessive computer and video game playing among children is being critically
      discussed from a pedagogic and public health point of view. To date, no reliable
      data for this phenomenon in Germany exists. In the present study, the excessive
      usage of computer and video games is seen as a rewarding behavior which can, due
      to learning mechanisms, become a prominent and inadequate strategy for children
      to cope with negative emotions like frustration, uneasiness and fears. In the
      survey, 323 children ranging in age from 11 to 14 years were asked about their
      video game playing behavior. Criteria for excessive computer and video game
      playing were developed in accordance with the criteria for dependency and
      pathological gambling (DSM-IV, ICD-10). Data show that 9.3% (N = 30) of the
      children fulfill all criteria for excessive computer and video game playing.
      Furthermore, these children differ from their class mates with respect to
      watching television, communication patterns, the ability to concentrate in school
      lectures and the preferred strategies coping with negative emotions. In
      accordance with findings in studies about substance-related addiction, data
      suggest that excessive computer and video game players use their excessive
      rewarding behavior specifically as an inadequate stress coping strategy.

PMID- 15875759
TI  - Treatment for soft tissue sarcoma in childhood and adolescence. Austrian results
      within the CWS 96 study.
AB  - OBJECTIVE: The aim of the CWS 96 Study was to achieve an optimal treatment in
      children and adolescents with soft tissue sarcoma (STS) implementing a further
      refinement of risk-adapted allocation to chemotherapy, surgery and radiotherapy.
      METHODS: Treatment stratification was based on tumour histology, TNM status,
      postsurgical stage, localisation and age. Local tumour control was ensured by
      surgery and risk-adapted radiotherapy. RESULTS: From 1995 to 2002, 89 patients
      were registered in Austria. The 3-year event-free survival (EFS) and overall
      survival rates (OS) were 63% +/- 6% and 71% +/- 6%, respectively. 59/89 patients
      had localised RMS-like (rhabdomayosarcoma) STS (EFS 73% +/- 7%), 14 had localised
      NON-RMS STS (EFS 54% +/- 16%) and 15 patients had metastatic disease at diagnosis
      (EFS 33% +/- 12%), 1 patient had fibromatosis. The EFS rates at 3 years in
      patients with localised RMS-like tumours according to risk group were 92% +/- 8%
      for low and standard risk (12 patients) and 67% +/- 8% for high risk (47
      patients). Favourable primary tumour sites of nonmetastatic RMS-like STS i.e.
      orbit, head/neck nonparameningeal or genitourinary non-bladder/prostate were
      diagnosed in 15 patients (1/15 patients died). In 44 patients with unfavourable
      localisation such as parameningeal, genitourinary bladder/prostate, extremity and
      others, 7 deceased. The 3 year EFS according to histology in patients with RMS
      like STS was 61% +/- 11% for RME (embryonal RMS ) (28 patients) and 71% +/- 15%
      for RMA (alveolar RMS) (10 patients). The most common treatment failure was local
      relapse occurring in 21% of patients in the high-risk group. CONCLUSION: Risk
      adapted individualisation of treatment led to a reduction of chemotherapy in the
      low and standard risk group without compromising survival. The outcome of RME and
      RMA was similar in this cohort of patients. These preliminary results after a
      median observation time of 2.5 years confirm the CWS 96 strategy.

PMID- 15875760
TI  - The link between angiotensin-converting enzyme genotype and pulmonary artery
      pressure in patients with COPD.
AB  - OBJECTIVE: The insertion (I)/deletion (D) polymorphism of the angiotensin
      converting enzyme (ACE) gene has been associated with an increased risk of
      cardiovascular diseases. In patients with primary pulmonary hypertension, the
      homozygous ACE DD genotype is more prevalent than the non-DD genotype. However,
      the relationship of ACE gene polymorphism to secondary pulmonary hypertension
      remains unclear, and ethnicity may be one of the factors that can modulate the
      effects of ACE genotypes reported in different studies. We hypothesized that in
      patients with chronic obstructive pulmonary disease (COPD) the presence of the D
      allele in the ACE gene polymorphism is associated with increased pulmonary artery
      pressure (Ppa). PATIENTS AND METHODS: Bodyplethysmography was used to assess lung
      function in 66 consecutive patients with COPD; pulmonary artery pressures were
      determined using echocardiography. ACE gene I/D polymorphism was identified with
      the polymerase chain reaction. 118 healthy persons served as the control group.
      All patients and controls were Caucasian. Genotype II was identified in 15
      patients with COPD, genotype ID in 31 and genotype DD in 20. In the control
      group, genotype II was identified in 19 persons, genotype ID in 68 and genotype
      DD in 31. The distribution of ACE gene polymorphism did not differ between
      patients and the control group. RESULTS: In patients with COPD, no differences
      were seen between the three genotype groups in mean age, smoking history,
      hemoglobin concentrations or ventilometric or blood gas variables. Both systolic
      and mean Ppa differed significantly between the II, ID and DD groups (Systolic
      Ppa: 24.4 +/- 2.2 versus 31.3 +/- 2.5 and 36.7 +/- 3.9 mm Hg, respectively,
      ANOVA, p < 0.05; Mean Ppa: 13.0 +/- 1.5 versus 17.5 +/- 1.4 and 21.2 +/- 2.8 mm
      Hg, respectively, ANOVA, p < 0.05). In multiple linear regression analysis, the
      I/D ACE gene polymorphism (p < 0.05), SaO2 (p < 0.05) and the duration of COPD (p
      < 0.02) were independent predictors of systolic and mean Ppa. CONCLUSION: The
      results of the study suggest that I/D ACE gene polymorphism is linked to
      pulmonary artery pressure in Caucasian patients with COPD.

PMID- 15875761
TI  - Surgical therapy options in polycystic liver disease.
AB  - INTRODUCTION: Polycystic liver disease (PLD) is a rare affliction frequently
      observed in association with polycystic kidney disease. Only symptomatic patients
      require treatment, which can be conservative or surgical, i.e. laparoscopic or
      conventional. We report the results of our experience in the surgical management
      of polycystic liver disease. METHODS: Between 1994 and 2003, 19 patients (16
      female, 3 male) were referred to our center for the management of PLD. Their
      median age was 50 years (range 33-72). All were symptomatic and their cysts had a
      median diameter of 11 cm (range 5-22). RESULTS: Laparoscopic management was
      undertaken in eight patients, with one conversion to open technique because of
      bleeding from a superficial hepatic vein. An open procedure was performed in 11
      patients: one left hemihepatectomy, deroofing in two patients, segment resection
      2/3 plus deroofing in six patients, and segment resection 5/6 plus deroofing in
      two patients. Four patients had complications: one case of biliary leakage was
      managed conservatively; two patients had pneumothorax caused by the cava catheter
      inserted for anesthesia, and one patient's abdominal drain tore off and had to be
      removed by relaparotomy on the fourth postoperative day. Median follow-up of all
      patients was 49 months (range 7-98). In one patient there was symptomatic
      recurrence with hepatomegaly and compression of the inferior vena cava 84 months
      after the first operation. CONCLUSIONS: Careful selection of patients and
      meticulous surgical technique are recommended in the management of PLD. The
      treatment of choice for symptomatic Gigot or Morino type 1 PLD is laparoscopic
      surgery, and for advanced stage PLD combined hepatic resection and cyst
      fenestration.

PMID- 15875762
TI  - Prevalence and incidence of Lyme borreliosis among Slovene forestry workers
      during the period of tick activity.
AB  - OBJECTIVES: To establish the prevalence and incidence of symptomatic and
      asymptomatic infection with Borrelia burgdorferi sensu lato during the period of
      tick activity, to compare the risk of infection with B. burgdorferi s.l. for
      forestry workers and indoor workers in Slovenia, and to compare the outcome of an
      in-house immunofluorescent assay (IFA) and a commercially available enzyme-linked
      immunosorbent assay (ELISA). METHODS: The study included 122 forestry workers;
      the control group consisted of 93 indoor workers. All participants were examined
      twice in 2002: before the beginning of tick activity (March) and at the end of
      tick activity (November). At each examination, principal demographic and
      epidemiological data were collected and a blood sample taken for serological
      analysis. Specific IgM and IgG antibodies against B. burgdorferi s.l. in the
      paired sera were determined with an in-house IFA and a commercially available
      ELISA flagellin test (DAKO). RESULTS: 9.8% of the forestry workers and 4.3% of
      the indoor workers tested positive for IgG with the IFA (p = 0.26); 23.8% of the
      forestry workers and 9.7% of the indoor workers tested positive for IgG with the
      ELISA (p = 0.02). During the study period the incidence of symptomatic Lyme
      borreliosis was 2.3% and the rate of IgG and/or IgM seroconversion of 10.2% was
      the same with both tests. CONCLUSIONS: The seroprevalence of antibodies against
      B. burgdorferi s.l. among the Slovene forestry workers was greater than among the
      indoor workers, but the difference between the two groups was not significant
      when the IFA was used. The incidence of Lyme borreliosis during the period of
      tick activity was lower than we expected, with a large proportion of
      seroconversions being asymptomatic.

PMID- 15875763
TI  - The role of dental evaluation and cephalometric analysis in the diagnosis of
      Williams-Beuren syndrome.
AB  - Williams-Beuren syndrome (WS) is a genetic condition with an incidence of 1 in
      20,000-50,000 live births. The syndrome consists of supravalvular aortic
      stenosis, characteristic dysmorphic facial features named "elf face" and
      intellectual disability. Early diagnosis of the syndrome is important since many
      of its features require treatment, and the prognosis can be dramatically improved
      by early recognition and management. This developmental disorder is well known to
      be clinically heterogeneous, making diagnosis difficult if based on the clinical
      picture. However, genetic testing is expensive and it is not cost effective to
      screen all patients based on clinical suspicion. Our goal was to develop a novel
      clinical screening method that would be sensitive, specific, inexpensive and
      readily available. We performed cephalometric analysis and dental evaluation of
      33 patients with genetically proven WS. Cephalometric analysis of soft tissues
      showed that with normal SNA, SNB and ANB angles, the lips were in front of the
      line of harmony. This finding was present in all WS patients (n = 33) but in none
      of the age-matched controls (n = 100). No other differences were found between WS
      and control patients. This cephalometric finding is specific and sensitive for WS
      and can be used in the diagnostic procedure, whereas none of the conventional
      dental evaluations are useful.

PMID- 15875764
TI  - Listeria meningitis in transplant recipients.
AB  - INTRODUCTION: Meningitis is a rare complication following organ and stem-cell
      transplantation and can be caused by a variety of microorganisms. AIM: To
      retrospectively review the clinical course and outcome of five cases of
      listeriosis in four organ recipients and one stem-cell recipient during a seven
      year period. PATIENTS AND METHODS: Patient records for more than 3500 patients
      undergoing organ or stem-cell transplantation at the university hospital of
      Innsbruck during a 27-year period were evaluated. Standard immunosuppression
      consisted of calcineurin inhibitor-based triple drug therapy with or without ATG
      or IL2 receptor antagonist induction. RESULTS: The first case affected a 35-year
      old woman who received an allogenic bone marrow transplant for advanced breast
      cancer. Cases two and three related to two male heart recipients. Cases four and
      five were diagnosed in one male and one female renal recipient. Listeria
      monocytogenes was isolated from blood in two cases and from cerebrospinal fluid
      in three. Treatment consisted of ampicillin in all cases with the addition of
      tobramycin (1), TMPS (1), meropenem (2) or imipenem/cilastatin (1). The deaths of
      two patients were directly related to L. monocytogenes. CONCLUSIONS: Although
      listeriosis is a rare complication following transplantation, this infection
      should be ruled out in individuals presenting with neurological symptoms and
      fever.

PMID- 15875765
TI  - Rapidly progressive dysphagia caused by Forestier's disease: a case report.
AB  - Forestier's disease is a systemic rheumatologic abnormality of unknown etiology,
      characterized by a flowing ossification of the anterior ligament of the spine. In
      this case study we report on an atypical appearance of Forestier's disease in a
      72-year-old woman. This patient had a one-month history of rapidly progressing
      dysphonia and dyspnea and at the time of admission was unable to eat. She had
      been operated for gastric and colon carcinoma seventeen months earlier. Total
      body CT scans showed a flowing ossification of the anterior ligament between
      levels C2 and C7 and an osteophyte protruding in the ventral direction at level
      C2. Before the osteophyte's removal, a tumor screening was conducted to exclude
      the presence of distant metastases or occult malignancy. Resection of the large
      osteophyte was performed via a typical ventral-cervical approach with horizontal
      skin incision. Six months after the procedure, the patient experienced distinct
      improvement of her condition and was able to eat both pulpy and solid foods
      again. In this case example, a rapidly progressive dysphagia was not caused by
      secondary malignancy, as initially speculated, but resulted from a ventral
      cervical osteophyte, considered a rare cause for acute development of severe
      dysphagia. Early diagnosis of Forestier's disease in this patient led to
      immediate surgical intervention, which proved to be adequate treatment and
      enabled the patient to make a good recovery.

PMID- 15875766
TI  - Effects of prepubertal exposure to xenoestrogen on development of estrogen target
      organs in female CD-1 mice.
AB  - BACKGROUND: There have been no previous reports comparing the effects of
      prepubertal xenoestrogen exposure on development of the reproductive tract and
      mammary glands in female mice. The effects of genistein (GEN), resveratrol (RES),
      zearalenone (ZEA), zeranol (ZER), bisphenol A (BPA) and diethylstilbestrol (DES)
      were examined. MATERIALS AND METHODS: Beginning at 15 days of age, female CD-1
      mice were administered 4 daily subcutaneous injections of 10 mg/kg/day of GEN,
      RES, ZEA, ZER or BPA, or 10 microg/kg/day of DES dissolved in dimethylsulfoxide
      (DMSO), or DMSO vehicle. Vaginal opening was checked; estrous cyclicity was
      monitored from 5, 9 or 21 weeks of age for 21 consecutive days; 6 animals per
      group were autopsied at 4, 8 and 24 weeks of age. RESULTS: Prepubertal exposure
      to GEN, ZEA, ZER and DES (but not RES or BPA) accelerated puberty onset (vaginal
      opening). Vaginal smears indicated that all xenoestrogen-treated mice were
      cycling, but ZEA-, ZER- and DES-treated mice spent more time in estrus. At 4
      weeks of age, absence of corpora lutea (anovulatory ovary) was observed in the
      untreated controls (33%, 2/6) and the GEN (50%, 3/6), RES (50%, 3/6), ZEA (100%,
      6/6), ZER (100%, 6/6), BPA (83%, 5/6) and DES groups (100%, 6/6). At 8 weeks of
      age, absence of corpora lutea was observed in the ZEA (33%, 2/6) group. Corpora
      lutea were present in all mice sacrificed at 24 weeks of age. Groups that
      received prepubertal xenoestrogen injections exhibited no morphological
      abnormalities of the uterus and vagina, and exhibited mammary gland growth
      similar to that of the untreated controls at all time-points. CONCLUSION: GEN,
      ZEA, ZER and DES (but not RES or BPA) caused early vaginal opening; mice exposed
      to ZEA, ZER or DES spent more time in the estrus phase; ZEA-treated mice had a
      longer period of anovulatory ovary than other xenoestrogen-treated mice; however,
      none of the xenoestrogens tested altered the uterine or vaginal morphology or
      mammary gland growth.

PMID- 15875767
TI  - Electroacupuncture and moxibustion influence the lipopolysaccharide-induced TNF
      alpha production by macrophages.
AB  - The purpose of this study was to evaluate the modifying effects of
      electroacupuncture (EA) and moxibustion (Mox) through the communication networks
      of the neuroimmune system using the two-step bacterial stimulation method. When
      EA or Mox treatment was implemented immediately following injection of the
      Streptococcus pyogenes preparation OK-432, a significant suppression of the tumor
      necrosis factor (TNF)alpha production by the peritoneal macrophages induced by
      lipopolysaccharide (LPS 1 microg/ml) was observed. When the stimulation with EA
      or Mox was reduced in volume, the degree of suppression decreased
      correspondingly. Naloxone antagonized to some extent the suppression of TNFalpha
      induced by EA, but did not compete with the suppression of TNFalpha release
      induced by Mox. These results suggest that activated macrophages are an important
      target of the immuno-suppressive effects of EA and Mox and that mu-opioid
      receptor-mediated mechanisms are responsible, to some extent, for the suppressive
      effect of EA, although Mox may not be dependent on these mechanisms.

PMID- 15875768
TI  - Differential modulation of integrin expression in chondrocytes during expansion
      for tissue engineering.
AB  - Cartilage tissue engineering has an important role to play in the generation of
      graft material for reconstructive surgery. In cultured chondrocytes, the
      dedifferentiation of cells seems unavoidable for multiplication. Dedifferentiated
      cells produce matrix of less quality. Normal cartilage is composed of
      chondrocytes, which are embedded within an extracellular matrix (ECM). The ECM
      plays a key role in controlling cellular characteristics and contains the
      integrins as a large family of heterodimeric cell adhesion receptors involved in
      cell-cell and cell-matrix interactions. In this study, the characteristic changes
      of integrin expression and expression of matrix proteins during the course of
      dedifferentiation of chondrocytes in cell culture for 1, 6 and 21 days, analyzed
      at the mRNA level by microarray analysis and at the protein level by
      immunohistochemistry, are described. The components of the fibronectin receptor,
      integrin beta1,alpha5, in conjunction with the ligand fibronectin, were up
      regulated during dedifferentiation. Integrin beta3 was expressed in the grey
      area. The components of the vitronectin-receptor, integrin alpha2b, alpha v, as
      well as integrin beta5, were activated on day 21, but neither vitronectin nor
      osteopontin were expressed by the cells. With ongoing dedifferentiation,
      activation of the GPIIb/GPIIIa receptor was found. The integrins beta2, beta4,
      beta6, beta8 and alpha2, alpha4, alpha6, alpha7 and alpha11 were never expressed.
      ILK, CD47 and ICAP1, as components of the intracellular signalling cascade of
      several integrins, were activated with ongoing dedifferentiation. In conclusion,
      a candidate for signal transmission during dedifferentiation is the fibronectin
      receptor (integrin alpha5beta1) in conjunction with its ligand fibronectin. Other
      receptors, e.g. for vitronectin and osteopontin (alphaVbeta3) or laminin
      (alpha6beta1) or their ligands, do not seem to be involved in signal transmission
      for dedifferentiation. In addition, the GPIIb/IIIa-receptor seems to assist the
      process of dedifferentiation. Intracellularly, ILK, ICAP1 and CD47 might assist
      the transduction of the integrin-dependent signals.

PMID- 15875769
TI  - Amifostine has an inhibitory effect on the radiation-induced p53-branched cascade
      in the immature mouse ovary.
AB  - The organic thiophosphate, amifostine, is a promising pharmacological compound
      showing selective protection in many tissues against the toxic side-effects of
      radiation and cytotoxic drugs. The aim of the present study was to assess the
      radioprotective effects of amifostine on ovarian follicles. Three-week-old female
      mice, with or without pretreatment with amifostine, were irradiated with 6.42 Gy
      of gamma-ray. Reduced proliferation of granulosa cells was verified with BrdU
      staining and the incidences of follicular degeneration increased in ovarian
      follicles in the gamma-ray-irradiated mice compared to that of the control or
      amifostine-treated group. Biochemical changes caused by gamma-irradiation
      provoked a rise of p53 and Bax protein and a decline of the inactive form in
      caspase-3 and PARP protein. Caspase-3 and PARP cleaved into active peptides
      during apoptosis. This process was confirmed by the result of this study, which
      was that the amount of the stable form decreased immediately after irradiation.
      In the amifostine treatment group before irradiation, the increased rate of p53
      and Bax was suppressed, particularly in the LDs-treated group. The relationship
      between PARP and caspase-3 levels showed the effect of amifostine exposure before
      irradiation. In conclusion, amifostine had an inhibitory effect on ovarian
      programmed cell death induced by gamma-ray, affecting the expression of apoptotic
      signaling molecules and the level of proliferation of the granulosa cells.

PMID- 15875770
TI  - Effects of vaccinia virus anti-inflammatory protein 35K and TIMP-1 gene transfers
      on vein graft stenosis in rabbits.
AB  - BACKGROUND: Vein graft stenosis is a common problem after bypass surgery. Vein
      grafts are ideal targets for gene therapy because transduction can be made ex
      vivo before grafting. Since chemokines and inflammatory factors are involved in
      vein graft thickening, we tested a hypothesis that the vaccinia virus anti
      inflammatory protein 35K which can sequester CC-chemokines, can reduce vein graft
      thickening in vivo. MATERIALS AND METHODS: We used adenovirus-mediated gene
      transfer (1x10(9) pfu/ml) of 35K and compared its effects on reducing stenosis in
      a rabbit jugular vein graft model with tissue inhibitor of metalloproteinase-1
      (TIMP-1) and LacZ control gene. TIMP-1 was used in this study because it has
      previously been shown to inhibit vein graft stenosis in other model systems. The
      expression of transgenes in the transduced segments was confirmed by RT-PCR. Vein
      grafts were analyzed using immunohistological and morphometric methods at the
      three-day time-point and at two-week and four-week time-points. RESULTS: It was
      found that the anti-inflammatory protein 35K was an efficient factor in reducing
      neointima formation at the two-week time-point, indicating that inflammatory
      factors play an important role in vein graft stenosis. At the four-week time
      point, 35K still showed a reduced accumulation of macrophages. TIMP-1 also tended
      to reduce neointimal thickening at the two-week time-point as compared to LacZ.
      CONCLUSION: It was found that 35K is an efficient factor in reducing neointima
      formation, macrophage accumulation and proliferation in rabbit vein grafts after
      adenoviral ex vivo gene transfer.

PMID- 15875771
TI  - Novel agents in the treatment of non-small cell lung cancer: implications for
      neoadjuvant chemotherapy?
AB  - During recent years, we have seen an increasing awareness among physicians about
      the possibilities of helping patients stricken by non-small cell lung cancer
      using active intervention with chemotherapeutics. This has emerged mainly from
      the development of new chemotherapeutics and novel drug combinations with an
      improved therapeutic ratio better tolerated by the patients. However, these new
      combinations of chemotherapeutics have proved to be only marginally better in
      terms of survival than the earlier used cytotoxic agents. Thus, many clinicians
      consider the effects of systemic therapy on symptom control and improved quality
      of life to be at least as important as survival when evaluating new drugs or new
      combinations. It is also obvious that improvements using traditional cytotoxics
      are slow and that there is a need for novel approaches. The present review
      focuses on novel drugs that have recently been introduced, or soon await to be
      included, in the management of advanced lung cancer and which have a potential
      value for use in neoadjuvant treatment of patients with non-small cell lung
      cancer, i.e. pemetrexed, EGFR-inhibiting agents, anti-angiogenesis inhibitors and
      other small molecules.

PMID- 15875772
TI  - Suppression of invasion of a hamster pancreatic cancer cell line by antisense
      oligonucleotides mutation-matched to K-ras gene.
AB  - The anti-invasive activity of antisense oligonucleotides (ASO) specific to the K
      ras gene in hamster pancreatic cancer was investigated. HaP-T1, a cell culture
      derived from BHP-induced hamster pancreatic cancer, was used. After liposome
      mediated transfection with mutation-matched and mutation-mismatched ASO in
      different concentrations, cell proliferation was studied by MTT and MTT-agarose
      methods. In vitro chemoinvasion assay with the reconstitution of a matrix of a
      basement membrane onto a filter in a Boyden chamber was performed. Mutation
      matched ASO inhibited the tumor growth and invasiveness of HaP-T1 in a dose
      dependent manner, while mutation-mismatched ASO were not effective in inhibiting
      invasion. The present study suggests that antisense oligonucleotides mutation
      matched to the K-ras gene may be a new anticancer strategy for pancreatic cancer
      since they inhibited not only tumor growth but also invasiveness in vitro.

PMID- 15875773
TI  - In vitro and in vivo antimycobacterial activity of an antihypertensive agent
      methyl-L-DOPA.
AB  - Methyl-L-DOPA, an antihypertensive agent, has significant in vitro activity
      against a variety of atypical mycobacteria such as the Mycobacterium avium
      complex, M. scrofulaceum, M. xenopi and M. marinum, and rare pathogens like M.
      fortuitum. In the present investigation, the screening of the in vitro activity
      was further extended by testing the in vitro activity against a total of 53
      different strains of mycobacteria, including 34 clinical isolates of both drug
      sensitive and drug-resistant Mycobacterium tuberculosis. Most of the strains were
      inhibited at 10-25 microg/mL concentrations of the drug. When methyl-L-DOPA was
      injected into male mice at a concentration of 10 microg/g body weight (20 g
      each), methyl-L-DOPA significantly protected them when challenged with a 50
      median lethal dose of M. tuberculosis H37Rv102. According to the chi2 test, the
      in vivo data were highly significant (p<0.01).

PMID- 15875774
TI  - Subglottic tracheal stenosis as primary manifestation of a marginal zone B-cell
      lymphoma of the larynx.
AB  - BACKGROUND: More than 90% of laryngeal tumors are squamous cell carcinomas.
      Primary hematopoetic neoplasms of the larynx are rare, being mainly
      extramedullary plasmocytoma and non-Hodgkin's lymphoma (NHL). These are mainly
      located in the supraglottic and glottic area, with only a few reported in the
      subglottic region. CASE REPORT: We report on a 58-year-old man, who presented at
      our clinic with severe dyspnea. On microlaryngoscopy, a subglottic stenosis at
      the level of the cricoid cartilage was found. The biopsy revealed the diagnosis
      of a MALT-type lymphoma (marginal zone B-cell lymphoma). The tracheostomy was
      followed by locoregional radiotherapy. CONCLUSION: This is the first report of a
      subglottic MALT-type lymphoma causing a tracheal stenosis. The preferred
      treatment is locoregional radiotherapy including the draining lymph nodes.

PMID- 15875775
TI  - Morphological and biochemical changes of andrographolide-induced cell death in
      human prostatic adenocarcinoma PC-3 cells.
AB  - Andrographolide was extracted and purified from Andrographis panicula using
      hexane and water partitioning followed by ethyl acetate extraction and
      chromatography. It showed selective cytotoxicity to prostate cancer PC-3 cells in
      vitro. The morphological and biochemical changes induced by the extract in
      carcinoma PC-3 cell death were studied. In andrographolide-treated cells,
      evidence of apoptosis such as cell shrinkage and surface microvilli loss after 4
      hour treatment and chromatin condensation and fragmentation in H&E-stained cells
      between 4 to 8 hours after treatment were observed. Under electron microscopy,
      membrane blebbing and apoptotic bodies formation were seen after 8-hour
      treatment. Using immunocytochemistry staining and cellular caspase-3 activity
      assay, andrographolide-treated cells showed considerable caspase-3 activation and
      caspase-8 in PC-3 cells at 4 and 2 hours after treatment, respectively. This
      suggests andrographolide-induced cell death was achieved through the apoptotic
      pathway, via the activation of an extrinsic caspase cascade.

PMID- 15875776
TI  - Carcinogenic potential of trans-2-hexenal is based on epigenetic effect.
AB  - BACKGROUND: Trans-2-hexenal (2-hexenal) is an alpha,beta-unsaturated carbonyl
      compound protecting plants against harmful substances. Since humans have a
      permanent intake of 2-hexenal via vegetable products, this genotoxic and
      mutagenic compound is considered to play a role in human carcinogenicity.
      MATERIALS AND METHODS: Ha-ras and p53 gene expression changes and tumor
      development were investigated in mice and rats after 2-hexenal administration.
      RESULTS: 2-Hexenal exposure did not result in gene expression alterations 24, 48
      or 72 hours after administration while 10 out of the 72 mice and rats included in
      the long-term study developed a malignancy by the end of the 18-month follow-up.
      CONCLUSION: Our results suggest that, although 2-hexenal showed no effect on the
      expression of the investigated onco- and suppressor genes, it has a marked
      carcinogenic potential, which may be explained only by an epigenetic effect of
      the compound.

PMID- 15875777
TI  - Household electromagnetic fields and breast cancer in elderly women.
AB  - The relationship between the rate of household low-frequency electromagnetic
      fields (EMF) and incidences of mammary tumors was studied in 1290 clinical case
      records of female patients aged 60 and more over a period of 26 years, based on
      the materials of the Edith Wolfson Medical Center, Israel. The studied material
      was divided into two groups, each corresponding to a period of 13 years. Group I
      included patients with mammary tumors under observation from 1978 to 1990, who
      rarely used EMF-generating appliances. Group II consisted of patients being under
      observation in the period between 1991 and 2003, characterized by much more
      extensive use of personal computers (more than 3 hours a day), mobile telephones,
      television sets, air conditioners and other household electrical appliances
      generating EMF. 200,527 biopsy and surgery samples were analyzed. Mammary tumors
      were found in 2824 women (1.4%), of which 1290 cases (45.6%) were observed in
      elderly women. Most of the observed tumors--1254 (97.2%)--were epithelial
      neoplasms. Mammary tumors were found in 585 elderly women in Group I and 705
      women in Group II. The case records of these patients showed that 114 elderly
      women (19.5%) in Group I and 360 (51.1%) in Group II were regularly exposed to
      EMF (mostly from personal computers) for at least 3 hours a day (chi2=57.2,
      p<0.001). There was a statistically significant influence of EMF on the formation
      of all observed epithelial mammary tumors in Group II. This influence is most
      evident for invasive ductal carcinomas, which was the commonest form of cancer in
      elderly women.

PMID- 15875778
TI  - Drug-induced cardiotoxicity studied by longitudinal B-type natriuretic peptide
      assays and radionuclide ventriculography.
AB  - BACKGROUND: To study the longitudinal variations of plasma B-type natriuretic
      peptide (BNP) with reference to left ventricular ejection fraction (LVEF) during
      and after chemotherapy with cardiotoxic drugs. PATIENTS AND METHODS: We
      prospectively measured plasma BNP using an immunoradiometric assay in 12
      anthracycline-treated breast cancer patients monitored for a mean time of 880+/
      293 days (pilot group). Prior to each cycle and throughout the following year,
      LVEF and cardiac output were measured by radionuclide ventriculography.
      Anthracycline pharmacokinetics was studied during the first cycle. Relationships
      between serial observations were analysed with the general linear mixed effects
      model. Identical methods were subsequently applied to a test group of 67
      anthracycline or trastuzumab-treated patients. RESULTS: Five out of 70 (6.33%)
      patients developed anthracycline-induced heart failure. BNP concentrations were
      found to be positively correlated to anthracycline cumulative dose and negatively
      to LVEF values. Variables entering the mixed models were cumulative anthracycline
      dose, time and cardiac output. CONCLUSION: An infra-clinical cardiotoxicity of
      anthracyclines as defined by BNP elevation is frequent but reversible. Patients
      who developed heart failure showed a continuous BNP increase and concentrations
      over 100 ng/ml.

PMID- 15875779
TI  - Cytotoxic effect of Laxaphycins A and B on human lymphoblastic cells (CCRF-CEM)
      using digitised videomicrofluorometry.
AB  - Laxaphycin A (laxa A) and Laxaphycin B (laxa B), cyclic peptides isolated from
      the terrestrial blue-green alga Anabaena laxa or the marine cyanobacterium
      Lyngbya majuscula have antifungal and cytotoxic activities. We used numerical
      videomicrofluorometry and a protocol of multiple labelling with Hoescht 33342
      (nuclear DNA), Rhodamine 123 (mitochondria) and Nile Red (plasma membrane) to
      study the cytotoxicity of these substances in human lymphoblastic cells sensitive
      (CEM-WT) or resistant (CEM-VLB and CEM-VM1) to anticancer agents. The results
      indicate a low resistance index of 2 for CEM-VLB cells treated with laxa B or
      laxa A + lava B. For the three cell strains, following laxa B treatment, we
      observed an increase of a polyploid cell subpopulation that could result from the
      alteration of topoisomerase-II activity. On the contrary, the simultaneous
      treatment by laxa A and laxa B led to a decrease of that subpopulation with
      increasing laxa A doses. However, the effect of laxa A was less pronounced in the
      CEM-VM1 cells, which present a low intrinsic topoisomerase-II activity. For CEM
      VLB cells, the higher doses needed can be attributed to their MDR resistance.
      Though we observed a synergistic effect between laxa B and laxa A (the latter is
      inactive by itself), these results indicate a different mode of action for laxa B
      and laxa A + laxa B. A more precise study of the mode of action of these
      compounds is warranted.

PMID- 15875780
TI  - Transcriptome analysis of different multidrug-resistant gastric carcinoma cells.
AB  - Multidrug resistance (MDR) of human cancers is the major cause of failure of
      chemotherapy. To better understand the molecular events associated with the
      development of different types of MDR, two different multidrug-resistant gastric
      carcinoma cell lines, the MDR1/P-glycoprotein-expressing cell line EPG85-257RDB
      and the MDR1/P-glycoprotein-negative cell variant EPG85-257RNOV, as well as the
      corresponding drug-sensitive parental cell line EPG85-257P, were used for
      analyses of the mRNA expression profiles by cDNA array hybridization. Of more
      than 12,000 genes spotted on the arrays, 156 genes were detected as being
      significantly regulated in the cell line EPG85-257RDB in comparison to the non
      resistant cell variant, and 61 genes were found to be differentially expressed in
      the cell line EPG85-257RNOV Seventeen genes showed a differential expression
      level in both multidrug-resistant gastric carcinoma variants. The impact of these
      alterations in gene expression levels in different multidrug-resistant gastric
      carcinoma cell variants is discussed.

PMID- 15875781
TI  - The soluble p51 protein in cancer diagnosis, prevention and therapy.
AB  - The soluble p51 antigen alone, or in combination with the soluble p66 (as a
      preparation of the soluble tumour-associated antigens, sTAA) was shown to be
      useful in both cancer detection, prevention and therapy. CANCER DETECTION: In
      colon cancer patients with recurrent cancer, the blood level of p51 increased
      whereas the blood level of p66 did not change. The correlation and regression
      coefficients between the serum level of p51 protein and the progress in colon
      cancer were 0.48 and 0.88, respectively. In patients with melanoma, development
      of metastases significantly increased the blood levels of p51. The method was
      shown to be highly sensitive (92 to 96%) and moderately specific (42 to 65%) for
      the detection of different types of cancer, such as of the colon, uterus, ovary
      and breast, as well as melanoma. CANCER PREVENTION AND THERAPY: This was
      performed using a preparation of both p66 and p51 antigens. sTAA have both tumour
      preventive and tumour-suppressive effects on chemically-induced cancers of the
      colon, skin and mammary glands in rats and mice. sTAA promote suppression of rat
      mammary tumours by different anticancer drugs, such as cyclophosphamide,
      tamoxifen and 5-fluorouracil. This effect was shown to be connected with
      activation of the host's immune system, especially that which is responsible for
      the activity of T and B lymphocytes. CONCLUSION: We propose the follow-up of
      cancer patients in order to verify, as early as possible, recurrent cancer and
      perform preventive therapy of suspect cancer patients with their own sTAA as a
      kind of autoimmunotherapy. Moreover, in combination with anticancer drugs, sTAA
      may serve as a new tool in prevention of the toxic side-effects of chemotherapy.

PMID- 15875782
TI  - Influence of hepatocyte growth factor/scatter factor (HGF/SF) on fibroblast
      growth factor-2 (FGF-2) levels in external auditory canal cholesteatoma (EACC)
      cell culture.
AB  - BACKGROUND: In previous studies, we cited circulatory disorders and hypoxia as
      etiological factors for the formation of external auditory canal cholesteatoma
      (EACC) resulting in angiogenesis. Here, we investigate how the angiogenic factor
      hepatocyte growth factor/scatter factor (HGF/SF) influences the level of another
      angiogenic factor FGF-2. MATERIALS AND METHODS: After 16 to 72 hours of
      incubation with 20 ng/ml HGF/SF, levels of VEGF in the HGF/SF-treated and
      untreated culture was analyzed. We also investigated the influence of HGF/SF (20
      80 ng/ml) on the concentration of FGF-2. RESULTS: After 16 hours of incubation
      with HGF/SF at 20 ng/ml, FGF-2 was measured at 44.19 pg/ml (control: 42.24
      pg/ml). After 72 hours, FGF-2 was at 23.41 pg/ml (control: 14.83 pg/ml). After 24
      hours, 40 ng/ml HGF/SF showed the highest concentration of FGF-2. CONCLUSION: FGF
      2 levels were initially elevated after treatment with HGF/SF, however, further
      incubation did not show any increase. We assume that HGF/SF released FGF-2 in the
      matrix but did not induce FGF-2 expression. The most effective HGF/SF
      concentration was 40 ng/ml.

PMID- 15875783
TI  - The role of fine-needle aspiration biopsy in the management of patients with
      thyroid nodules.
AB  - Fine-needle aspiration biopsy (FNAB) of the thyroid gland is the most cost
      effective examination in the evaluation of thyroid nodules. The aim of this study
      was to present our experience from all patients who underwent thyroid FNA in the
      University Hospital of Ioannina, Greece, in the period 1993-2003, and its value
      in the diagnostic management of patients with thyroid nodules. FNA was performed
      in 900 patients of whom 753 were females and 147 males. The cases were classified
      according to diagnosis into five groups: benign/negative 628, primary carcinoma
      28, metastatic carcinoma 5, suspicious/indeterminate 60 and non-diagnostic 179.
      Cytological findings were compared with histopathological findings and the
      statistical analysis in our data yielded the following results: sensitivity
      92.1%, specificity 93.2%. These results are in accordance with the already
      published data in the international literature. In cases of differential
      diagnosis between adenomatoid hyperplasia and follicular neoplasia, four cases
      were diagnosed as hot nodules. In the benign group, three cases were diagnosed as
      nodular hyperplasia with cystic degeneration on FNA, but, after surgical
      treatment, histologically were diagnosed as papillary carcinomas. In the group of
      suspicious/indeterminate, two cases were diagnosed as suspicious for follicular
      neoplasia on FNA and, after surgical treatment, were diagnosed
      histopathologically as medullary carcinomas. In conclusion, we suggest that
      routine measurement of serum calcitonin is useful and mandatory in the detection
      of medullary carcinoma among patients with nodular thyroid diseases. Taking into
      consideration the clinical data can minimize false-positive and false-negative
      rates. We conclude that FNA is an effective screening test in the evaluation of
      the necessity for surgical treatment in patients with thyroid nodules.

PMID- 15875784
TI  - Novel insights into the mechanism of action of intravesical immunomodulators.
AB  - To date, the precise mechanism of intravesical immunomodulators remains unknown.
      In vitro, interferon alpha (IFN-alpha) acts directly on neoplastic cells and
      inhibits their proliferation while it induces their differentiation. Urothelium
      and transitional cell carcinoma (TCC) cells express IFN-alpha receptor, the
      density of which correlates with lesion grade. IFN-alpha reduces neo
      microvascular density in the normal urothelium adjacent to the tumor after
      transurethial resection (TUR), possibly via inhibition of COX-1. Moreover, IFN
      alpha induces the membrane expression of tumor-related antigens and MHC antigens,
      providing a basis for a cellular immune response. When given intravesically, IFN
      alpha may result in local and systemic T cell and NK cell activation. By
      monitoring nitric oxide (NO) end-products in urine and evaluating inducible
      nitric oxide synthase (iNOS) expression immunohistochemically, we were able to
      show that IFN-alpha may induce urothelial iNOS expression with subsequent
      formation of peroxynitrite, which might contribute to the antineoplastic action
      of IFN-alpha. Bacillus Calmette-Guerin (BCG) is thought to bind to the bladder
      wall via interaction between the bacterial antigen 85 complex and fibronectin.
      Although systemic reactions (evolution of cellular immune response, systemic
      production of cytokines and oxygen free radicals) have been reported, a likely
      scenario is that exposure to BCG results in a massive local immune response,
      characterized by induced expression of cytokines in the urine and in the bladder
      wall, and by a marked infiltration of the bladder wall by granulocytes and
      mononuclear cells. BCG-induced changes in tumor cell phenotype render them able
      to act both as lymphokine-alphactivated killer cell targets and antigen
      presenting cells. Although BCG may act directly on the proliferation of tumor
      cells, helper and cytotoxic T cells and, most probably, NK cells are absolutely
      necessary for any antitumor effects. Tumor cell killing is mediated through
      FasLigand, perforin and TNF-alpha. In a recent study, we found that BCG up
      regulated iNOS expression in normal human urothelium in vivo, suggesting a role
      for NO in BCG-mediated antitumor activity.

PMID- 15875785
TI  - In vivo and in vitro decondensation of human sperm and assisted reproduction
      technologies.
AB  - For a successful fertilization and pronucleus formation to occur, not only a
      properly condensed sperm nucleus, but also decondensation ability in the oocyte
      is important. The sperm abnormalities causing failure of sperm decondensation in
      the oocyte are unrecognizable by conventional semen analysis and different
      methods are used. The chromatin decondensation ability of the human spermatozoa
      in vivo and in vitro and its association with infertility and assisted
      reproduction techniques (ART) are clearly discussed in this paper. The factors
      affecting the decondensation ability of the human sperm are also mentioned. It is
      suggested that the methods currently used to assess sperm chromatin
      decondensation are of limited value in assessing fertilization and pregnancy
      rates after ART.

PMID- 15875786
TI  - Chemotherapy-induced allodinia: neuroprotective effect of acetyl-L-carnitine.
AB  - BACKGROUND: We tested the hypothesis that acetyl-L-carnitine (ALC) may have a
      protective and a curative role in chemotherapy-induced hyperalgesia in vivo, in
      animal models of cisplatin-, paclitaxel- and vincristine-induced neuropathy. In
      addition, the possible interaction between ALC and vincristine antineoplastic
      action was assessed. MATERIALS AND METHODS: Chemotherapy-induced peripheral
      neuropathy (CIPN) was induced in different groups of rats. The effect of ALC was
      evaluated both when its administration was started together with the
      administration of anticancer drugs ("preventive" protocol) and when ALC
      administration was started later on during treatment ("curative" protocol).
      RESULTS: The ALC treatment significantly prevented the lowering of the mechanical
      nociceptive threshold when the administration started concomitantly and,
      respectively, with cisplatin, paclitaxel and vincristine as compared to each drug
      alone. Furthermore, when ALC administration was started later on during
      treatment, at well-established neuropathy, ALC was able to restore the mechanical
      nociceptive threshold within a few days. Finally, experiments indicated that ALC
      does not interfere with the antitumor effects of vincristine. CONCLUSION:
      Considering the absence of any satisfactory treatment currently available for
      CIPN in a clinical setting, these are important observations, opening up the
      possibility of using ALC to treat a wide range of patients who have undergone
      chemotherapy and developed sensory peripheral neuropathy.

PMID- 15875787
TI  - Different pattern of metastasis in liver implanted pancreatic cancer between
      young and old Syrian golden hamsters.
AB  - We have previously reported on the "return trip" metastases from the liver to the
      pancreas in a hamster experimental pancreatic cancer model. Because the pancreas
      is the main metastatic site of liver-implanted pancreatic tumors, our aim was to
      clarify whether the metastatic sites differ in young and old tumor-bearing
      animals. HaP-T1, a continuous tissue-cultured cell line, derived from BHP-induced
      pancreatic adenocarcinoma, was implanted into the liver. The animals were divided
      into two groups: A) younger than 26 weeks and B) older than 26 weeks. Three
      animals from each group were sacrificed on Days 35, 42, 49, 56, 63, 70, 77, 84,
      91 and 98, to study the metastatic sites. Survival was also studied. After death,
      necropsy was performed. Resected and necropsied specimens were analyzed
      histopathologically and by PCR/RFLP analysis to confirm the presence of K-ras
      point mutation. The success rate of implantation was 100%. Survival was 102.3+/
      2.5 days in group A and 95.3+/-1.5 days in group B. Animals of group A,
      sacrificed weekly until Day 70, showed metastases only to the pancreas ("return
      trip"), while this phenomenon happened only in animals sacrificed on Day 35 in
      group B. In group A, on Days 77, 84, 91 and 98, metastases were also found in the
      kidneys, lymph nodes, ovary and testis. In hamsters of group B, metastases were
      found in multiple sites such as the pancreas, vas deferens, ovary and testis
      ("multiple journeys"). All intra-hepatically-implanted tumor and metastatic sites
      showed the K-ras point mutation. This homologous implantation model may be
      helpful for further research into the process of metastasis and its relationship
      with the immunological response.

PMID- 15875788
TI  - Skin cancer in the elderly.
AB  - With the significant increase in the average life-span in the industrial world,
      skin cancer has become a great health concern. There are various epidemiological,
      biological and molecular data suggesting that skin cancer is predominantly a
      disease of the elderly, since approximately 53% of skin cancer-related deaths
      occur in persons more than 65 years old. With regard to the management of elderly
      patients with skin cancer, this should be individualized depending upon the
      clinical performance status, and age alone should not constitute an obstruction
      for the administration of the optimal treatment. Since elderly patients with
      melanoma have a worse prognosis, emphasis should be given to primary and
      secondary prevention. Physicians treating elderly patients should be trained in
      an individualized approach to these patients and encouraged to participate in
      programs for the early detection of suspicious skin lesions.

PMID- 15875789
TI  - Automated variable weighting in k-means type clustering.
AB  - This paper proposes a k-means type clustering algorithm that can automatically
      calculate variable weights. A new step is introduced to the k-means clustering
      process to iteratively update variable weights based on the current partition of
      data and a formula for weight calculation is proposed. The convergency theorem of
      the new clustering process is given. The variable weights produced by the
      algorithm measure the importance of variables in clustering and can be used in
      variable selection in data mining applications where large and complex real data
      are often involved. Experimental results on both synthetic and real data have
      shown that the new algorithm outperformed the standard k-means type algorithms in
      recovering clusters in data.

PMID- 15875790
TI  - An integration of online and pseudo-online information for cursive word
      recognition.
AB  - In this paper, we present a novel method to extract stroke order independent
      information from online data. This information, which we term pseudo-online,
      conveys relevant information on the offline representation of the word. Based on
      this information, a combination of classification decisions from online and
      pseudo-online cursive word recognizers is performed to improve the recognition of
      online cursive words. One of the most valuable aspects of this approach with
      respect to similar methods that combine online and offline classifiers for word
      recognition is that the pseudo-online representation is similar to the online
      signal and, hence, word recognition is based on a single engine. Results
      demonstrate that the pseudo-online representation is useful as the combination of
      classifiers perform better than those based solely on pure online information.

PMID- 15875791
TI  - Acquiring linear subspaces for face recognition under variable lighting.
AB  - Previous work has demonstrated that the image variation of many objects (human
      faces in particular) under variable lighting can be effectively modeled by low
      dimensional linear spaces, even when there are multiple light sources and
      shadowing. Basis images spanning this space are usually obtained in one of three
      ways: A large set of images of the object under different lighting conditions is
      acquired, and principal component analysis (PCA) is used to estimate a subspace.
      Alternatively, synthetic images are rendered from a 3D model (perhaps
      reconstructed from images) under point sources and, again, PCA is used to
      estimate a subspace. Finally, images rendered from a 3D model under diffuse
      lighting based on spherical harmonics are directly used as basis images. In this
      paper, we show how to arrange physical lighting so that the acquired images of
      each object can be directly used as the basis vectors of a low-dimensional linear
      space and that this subspace is close to those acquired by the other methods.
      More specifically, there exist configurations of k point light source directions,
      with k typically ranging from 5 to 9, such that, by taking k images of an object
      under these single sources, the resulting subspace is an effective representation
      for recognition under a wide range of lighting conditions. Since the subspace is
      generated directly from real images, potentially complex and/or brittle
      intermediate steps such as 3D reconstruction can be completely avoided; nor is it
      necessary to acquire large numbers of training images or to physically construct
      complex diffuse (harmonic) light fields. We validate the use of subspaces
      constructed in this fashion within the context of face recognition.

PMID- 15875792
TI  - Active and dynamic information fusion for facial expression understanding from
      image sequences.
AB  - This paper explores the use of multisensory information fusion technique with
      Dynamic Bayesian networks (DBNs) for modeling and understanding the temporal
      behaviors of facial expressions in image sequences. Our facial feature detection
      and tracking based on active IR illumination provides reliable visual information
      under variable lighting and head motion. Our approach to facial expression
      recognition lies in the proposed dynamic and probabilistic framework based on
      combining DBNs with Ekman's Facial Action Coding System (FACS) for systematically
      modeling the dynamic and stochastic behaviors of spontaneous facial expressions.
      The framework not only provides a coherent and unified hierarchical probabilistic
      framework to represent spatial and temporal information related to facial
      expressions, but also allows us to actively select the most informative visual
      cues from the available information sources to minimize the ambiguity in
      recognition. The recognition of facial expressions is accomplished by fusing not
      only from the current visual observations, but also from the previous visual
      evidences. Consequently, the recognition becomes more robust and accurate through
      explicitly modeling temporal behavior of facial expression. In this paper, we
      present the theoretical foundation underlying the proposed probabilistic and
      dynamic framework for facial expression modeling and understanding. Experimental
      results demonstrate that our approach can accurately and robustly recognize
      spontaneous facial expressions from an image sequence under different conditions.

PMID- 15875793
TI  - Automatic image orientation detection via confidence-based integration of low
      level and semantic cues.
AB  - Automatic image orientation detection for natural images is a useful, yet
      challenging research topic. Humans use scene context and semantic object
      recognition to identify the correct image orientation. However, it is difficult
      for a computer to perform the task in the same way because current object
      recognition algorithms are extremely limited in their scope and robustness. As a
      result, existing orientation detection methods were built upon low-level vision
      features such as spatial distributions of color and texture. Discrepant detection
      rates have been reported for these methods in the literature. We have developed a
      probabilistic approach to image orientation detection via confidence-based
      integration of low-level and semantic cues within a Bayesian framework. Our
      current accuracy is 90 percent for unconstrained consumer photos, impressive
      given the findings of a psychophysical study conducted recently. The proposed
      framework is an attempt to bridge the gap between computer and human vision
      systems and is applicable to other problems involving semantic scene content
      understanding.

PMID- 15875794
TI  - Incremental model-based estimation using geometric constraints.
AB  - We present a model-based framework for incremental, adaptive object shape
      estimation and tracking in monocular image sequences. Parametric structure and
      motion estimation methods usually assume a fixed class of shape representation
      (splines, deformable superquadrics, etc.) that is initialized prior to tracking.
      Since the model shape coverage is fixed a priori, the incremental recovery of
      structure is decoupled from tracking, thereby limiting both processes in their
      scope and robustness. In this work, we describe a model-based framework that
      supports the automatic detection and integration of low-level geometric
      primitives (lines) incrementally. Such primitives are not explicitly captured in
      the initial model, but are moving consistently with its image motion. The
      consistency tests used to identify new structure are based on trinocular
      constraints between geometric primitives. The method allows not only an increase
      in the model scope, but also improves tracking accuracy by including the newly
      recovered features in its state estimation. The formulation is a step toward
      automatic model building, since it allows both weaker assumptions on the
      availability of a prior shape representation and on the number of features that
      would otherwise be necessary for entirely bottom-up reconstruction. We
      demonstrate the proposed approach on two separate image-based tracking domains,
      each involving complex 3D object structure and motion.

PMID- 15875795
TI  - A voting-based computational framework for visual motion analysis and
      interpretation.
AB  - Most approaches for motion analysis and interpretation rely on restrictive
      parametric models and involve iterative methods which depend heavily on initial
      conditions and are subject to instability. Further difficulties are encountered
      in image regions where motion is not smooth-typically around motion boundaries.
      This work addresses the problem of visual motion analysis and interpretation by
      formulating it as an inference of motion layers from a noisy and possibly sparse
      point set in a 4D space. The core of the method is based on a layered 4D
      representation of data and a voting scheme for affinity propagation. The inherent
      problem caused by the ambiguity of 2D to 3D interpretation is usually handled by
      adding additional constraints, such as rigidity. However, enforcing such a global
      constraint has been problematic in the combined presence of noise and multiple
      independent motions. By decoupling the processes of matching, outlier rejection,
      segmentation, and interpretation, we extract accurate motion layers based on the
      smoothness of image motion, then locally enforce rigidity for each layer in order
      to infer its 3D structure and motion. The proposed framework is noniterative and
      consistently handles both smooth moving regions and motion discontinuities
      without using any prior knowledge of the motion model.

PMID- 15875796
TI  - Learning viewpoint invariant perceptual representations from cluttered images.
AB  - In order to perform object recognition, it is necessary to form perceptual
      representations that are sufficiently specific to distinguish between objects,
      but that are also sufficiently flexible to generalize across changes in location,
      rotation, and scale. A standard method for learning perceptual representations
      that are invariant to viewpoint is to form temporal associations across image
      sequences showing object transformations. However, this method requires that
      individual stimuli be presented in isolation and is therefore unlikely to succeed
      in real-world applications where multiple objects can co-occur in the visual
      input. This paper proposes a simple modification to the learning method that can
      overcome this limitation and results in more robust learning of invariant
      representations.

PMID- 15875797
TI  - Precision range image registration using a robust surface interpenetration
      measure and enhanced genetic algorithms.
AB  - This paper addresses the range image registration problem for views having low
      overlap and which may include substantial noise. The current state of the art in
      range image registration is best represented by the well-known iterative closest
      point (ICP) algorithm and numerous variations on it. Although this method is
      effective in many domains, it nevertheless suffers from two key limitations: It
      requires prealignment of the range surfaces to a reasonable starting point and it
      is not robust to outliers arising either from noise or low surface overlap. This
      paper proposes a new approach that avoids these problems. To that end, there are
      two key, novel contributions in this work: a new, hybrid genetic algorithm (GA)
      technique, including hillclimbing and parallel-migration, combined with a new,
      robust evaluation metric based on surface interpenetration. Up to now,
      interpenetration has been evaluated only qualitatively; we define the first
      quantitative measure for it. Because they search in a space of transformations,
      GAs are capable of registering surfaces even when there is low overlap between
      them and without need for prealignment. The novel GA search algorithm we present
      offers much faster convergence than prior GA methods, while the new robust
      evaluation metric ensures more precise alignments, even in the presence of
      significant noise, than mean squared error or other well-known robust cost
      functions. The paper presents thorough experimental results to show the
      improvements realized by these two contributions.

PMID- 15875798
TI  - A parallel-line detection algorithm based on HMM decoding.
AB  - The detection of groups of parallel lines is important in applications such as
      form processing and text (handwriting) extraction from rule lined paper. These
      tasks can be very challenging in degraded documents where the lines are severely
      broken. In this paper, we propose a novel model-based method which incorporates
      high-level context to detect these lines. After preprocessing (such as skew
      correction and text filtering), we use trained Hidden Markov Models (HMM) to
      locate the optimal positions of all lines simultaneously on the horizontal or
      vertical projection profiles, based on the Viterbi decoding. The algorithm is
      trainable so it can be easily adapted to different application scenarios. The
      experiments conducted on known form processing and rule line detection show our
      method is robust, and achieves better results than other widely used line
      detection methods.

PMID- 15875799
TI  - Multiregion level-set partitioning of synthetic aperture radar images.
AB  - The purpose of this study is to investigate Synthetic Aperture Radar (SAR) image
      segmentation into a given but arbitrary number of gamma homogeneous regions via
      active contours and level sets. The segmentation of SAR images is a difficult
      problem due to the presence of speckle which can be modeled as strong,
      multiplicative noise. The proposed algorithm consists of evolving simple closed
      planar curves within an explicit correspondence between the interiors of curves
      and regions of segmentation to minimize a criterion containing a term of
      conformity of data to a speckle model of noise and a term of regularization.
      Results are shown on both synthetic and real images.

PMID- 15875800
TI  - A novel kernel method for clustering.
AB  - Kernel Methods are algorithms that, by replacing the inner product with an
      appropriate positive definite function, implicitly perform a nonlinear mapping of
      the input data into a high-dimensional feature space. In this paper, we present a
      kernel method for clustering inspired by the classical K-Means algorithm in which
      each cluster is iteratively refined using a one-class Support Vector Machine. Our
      method, which can be easily implemented, compares favorably with respect to
      popular clustering algorithms, like K-Means, Neural Gas, and Self-Organizing
      Maps, on a synthetic data set and three UCI real data benchmarks (IRIS data,
      Wisconsin breast cancer database, Spam database).

PMID- 15875801
TI  - Glasses removal from facial image using recursive error compensation.
AB  - In this paper, we propose a new method of removing glasses from a human frontal
      facial image. We first detect the regions occluded by the glasses and generate a
      natural looking facial image without glasses by recursive error compensation
      using PCA reconstruction. The resulting image has no trace of the glasses frame
      or of the reflection and shade caused by the glasses. The experimental results
      show that the proposed method provides an effective solution to the problem of
      glasses occlusion and we believe that this method can also be used to enhance the
      performance of face recognition systems.

PMID- 15875802
TI  - A video database of moving faces and people.
AB  - We describe a database of static images and video clips of human faces and people
      that is useful for testing algorithms for face and person recognition, head/eye
      tracking, and computer graphics modeling of natural human motions. For each
      person there are nine static "facial mug shots" and a series of video streams.
      The videos include a "moving facial mug shot," a facial speech clip, one or more
      dynamic facial expression clips, two gait videos, and a conversation video taken
      at a moderate distance from the camera. Complete data sets are available for 284
      subjects and duplicate data sets, taken subsequent to the original set, are
      available for 229 subjects.

PMID- 15875803
TI  - Clutter invariant ATR.
AB  - One of the central problems in Automated Target Recognition is to accommodate the
      infinite variety of clutter in real military environments. The principle focus of
      our paper is on the construction of metric spaces where the metric measures the
      distance between objects of interest invariant to the infinite variety of
      clutter. Such metrics are formulated using second-order random field models. Our
      results indicate that this approach significantly improves
      detection/classification rates of targets in clutter.

PMID- 15875804
TI  - Orientation in manhattan: equiprojective classes and sequential estimation.
AB  - The problem of inferring 3D orientation of a camera from video sequences has been
      mostly addressed by first computing correspondences of image features. This
      intermediate step is now seen as the main bottleneck of those approaches. In this
      paper, we propose a new 3D orientation estimation method for urban (indoor and
      outdoor) environments, which avoids correspondences between frames. The scene
      property exploited by our method is that many edges are oriented along three
      orthogonal directions; this is the recently introduced Manhattan world (MW)
      assumption. The main contributions of this paper are: the definition of
      equivalence classes of equiprojective orientations, the introduction of a new
      small rotation model, formalizing the fact that the camera moves smoothly, and
      the decoupling of elevation and twist angle estimation from that of the compass
      angle. We build a probabilistic sequential orientation estimation method, based
      on an MW likelihood model, with the above-listed contributions allowing a drastic
      reduction of the search space for each orientation estimate. We demonstrate the
      performance of our method using real video sequences.

PMID- 15875805
TI  - Effective gaussian mixture learning for video background subtraction.
AB  - Adaptive Gaussian mixtures have been used for modeling nonstationary temporal
      distributions of pixels in video surveillance applications. However, a common
      problem for this approach is balancing between model convergence speed and
      stability. This paper proposes an effective scheme to improve the convergence
      rate without compromising model stability. This is achieved by replacing the
      global, static retention factor with an adaptive learning rate calculated for
      each Gaussian at every frame. Significant improvements are shown on both
      synthetic and real video data. Incorporating this algorithm into a statistical
      framework for background subtraction leads to an improved segmentation
      performance compared to a standard method.

PMID- 15875806
TI  - Differential responses of proliferative and non-proliferative leukemia cells to
      oxidative stress.
AB  - The response of three human leukemia cell lines, the proliferative promonocyte
      THP-1 and the promyeloid HL60 cells and the non-proliferative phorbol ester
      treated HL60 cells (HL60/PMA), to oxidative stress induced by tert
      butylhydroperoxide (t-BHP) treatment was analyzed by fluorescence microplate
      assay, anti-oxidant enzyme activity measurements, high performance liquid
      chromatography, yopro-1/PI incorporation, poly (ADP-ribose) polymerase and
      caspase 3 cleavages. After t-BHP treatment, the non-proliferative HL60/PMA cells
      exhibited a weak increase in reactive oxygen species (ROS) production, a better
      preservation of thiol content, a decrease of glutathione peroxidase activity and
      a high ability to undergo necrosis rather than apoptosis. Submitted to the same
      treatment, the proliferative HL60 and THP-1 cells exhibited a high increase of
      ROS production, a moderate thiol depletion and a high percentage of apoptosis.
      Under thiol depleting conditions, the oxidative treatment of the HL60/PMA cells
      resulted in a high ROS production that reached levels similar to those of the two
      other cell lines and in cell death mainly by necrosis. In conclusion, these
      results that show proliferative phenotype is essential for cell response towards
      oxidative stress, are of particular interest in chemotherapy involving an
      oxidative mechanism.

PMID- 15875807
TI  - Differential effects of cysteine and methionine residues in the antioxidant
      activity of human serum albumin.
AB  - Antioxidant properties of human serum albumin (HSA) may explain part of its
      beneficial role in various diseases related to free radical attack. In the
      present study, the antioxidant role of Cys and Met was studied by copper-mediated
      oxidation of human low density lipoproteins and by free radical-induced blood
      hemolysis which essentially assessed metal-chelating and free radical scavenging
      activities, respectively. Mild conditions were set up to specifically modify Cys
      and Met residues by N-ethylmaleimide (NEM) and chloramine T treatments,
      respectively. We found that Met and Cys accounted for 40-80% of total antioxidant
      activity of HSA. Copper binding to HSA was decreased by about 50% with chloramine
      T treatment of Met whereas no change was observed after NEM treatment of Cys.
      Although other amino acid residues are likely to be involved in anti-/prooxidant
      properties of HSA, from our data, we propose that Cys chiefly works as a free
      radical scavenger whereas Met mainly acts as a metal chelator.

PMID- 15875808
TI  - Measurement of 8-oxo-7,8-dihydro-2'-deoxyguanosine in peripheral blood
      mononuclear cells: optimisation and application to samples from a case-control
      study on cancers of the oesophagus and cardia.
AB  - 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker to
      evaluate the level of oxidative stress. This study describes in its first part
      the optimisation of our analytical procedure (HPLC/electrochemical detection).
      Particular care was exercised to avoid artefactual oxidation and in the precision
      of measurement, which was evaluated with blood bags from hemochromatosis
      patients. The best results were obtained with a DNA extraction step using the
      "chaotropic method" recommended by the European Standards Committee on Oxidative
      DNA Damage (ESCODD). Other approaches such as anion exchange columns gave ten
      times as much 8-oxodG as this method. Moreover, a complete DNA hydrolysis using
      five different enzymes allowed improved precision. The optimised protocol was
      applied to peripheral blood mononuclear cells (PBMC) sampled during a case
      control study on cancers of the oesophagus and cardia. With 7.2 +/- 2.6 8
      oxodG/10(6) 2'-deoxyguanosines (2'-dG) (mean +/- SD), patients (n = 17) showed
      higher levels of 8-oxodG than controls (4.9 +/- 1.9 8-oxodG/10(6) 2'-dG, n = 43,
      Student's t-test: p < 0.001). This difference remained significant after
      technical (storage, sampling period, 2'-dG levels) and individual (age, sex,
      smoking, alcohol) confounding factors were taken into account (p < 0.0001,
      Generalised Linear regression Model). To our knowledge, this is the first report
      to demonstrate an increase of 8-oxodG in PBMCs of patients suffering from a
      cancer of the upper digestive tract. This elevated level of DNA damage in
      patients can raise interesting issues: is oxidative stress the cause or the
      result of the pathology? Could this biomarker be used to evaluate chemoprevention
      trials concerning digestive tract cancers?

PMID- 15875809
TI  - NAD(H) enhances the Cu(II)-mediated inactivation of lactate dehydrogenase by
      increasing the accessibility of sulfhydryl groups.
AB  - Copper ions are known to inactivate a variety of enzymes, and lactate
      dehydrogenase (LDH) is exceptionally sensitive to the presence of this metal. We
      now found that NADH strongly enhances the Cu(II)-mediated loss of LDH activity.
      Surprisingly, NADH was not oxidized in this process and also NAD+ promoted the
      Cu(II)-dependent inactivation of LDH. Catalase only partly protected the enzyme,
      whereas hypoxia even enhanced LDH inactivation. NAD(H) accelerated sulfhydryl
      (SH) group oxidation of LDH by 5,5-dithio-bis(2-nitrobenzoic acid) (DTNB), and,
      vice versa, LDH-mediated Cu(II) reduction. LDH activity was preserved by thiol
      donators and pyruvate and partially preserved by lactate and oxamate. Our results
      suggest that reactive oxygen species (ROS) are of minor importance for the
      inactivation of LDH induced by Cu(II)/NADH. We propose that conformational
      changes of the enzymes' active sites induced by NAD(H)-binding increase the
      accessibility of active sites' cysteine residues to Cu(II) thereby accelerating
      their oxidation and, consequently, loss of catalytic activity.

PMID- 15875810
TI  - Effect of complexation with randomly methylated beta-cyclodextrin on the aqueous
      solubility, photostability and antioxidant activity of an indolinonic nitroxide
      radical.
AB  - The interaction between the hydrophobic indolinonic nitroxide radical, 1,2
      dihydro-2-methyl-2-phenyl-3H-indole-3-one-1-oxyl and hydrophilic alpha-, beta-
      and gamma-cyclodextrin derivatives was investigated in water by phase-solubility
      analysis. Among the studied cyclodextrins, random methyl-beta-cyclodextrin (RM
      beta-CD) had the greatest solubilizing activity (1312-fold increase in. the
      intrinsic aqueous solubility). Solid complexes were prepared by the freeze-drying
      method and characterized by powder X-ray diffractometry and thermal analysis.
      Complexation of the nitroxide with RM-beta-CD was also confirmed in solution by
      electron paramagnetic resonance (EPR) spectroscopy. Photodegradation of the
      nitroxide was reduced by complexation with RM-beta-CD, this effect being more
      pronounced in the solid-state (the extent of degradation was 28.0% for the
      complex vs. 78.8% for uncomplexed nitroxide) than in solution (41.2 vs. 69.1% for
      uncomplexed nitroxide). The antioxidant activity of the complex was also
      investigated on the peroxidation of methyl linoleate micelles and on protein
      oxidation induced by free radical generators, and in both systems the free form
      of the nitroxide as well as its complex with RM-beta-CD, showed essentially the
      same degree of protection. Moreover, EPR experiments showed a time-dependent
      decrease in the EPR signal of both the complexed and uncomplexed nitroxides with
      the free-radical generators. Therefore, RM-beta-CD complexation of the nitroxide
      represents an effective strategy to improve its aqueous solubility and
      photostability, which is essential for certain biological applications, while it
      does not interfere with its radical scavenging efficiency.

PMID- 15875811
TI  - Urinary excretion of epsilondA is not predictive of cancer development: a
      prospective nested case-control study.
AB  - Human biomonitoring of the lipid peroxidation DNA modification 1,N6
      ethenodeoxyadenosine (epsilondA) excreted into urine is thought to be a potential
      marker for oxidative stress-related DNA damage and human cancer. We have tested
      this hypothesis in a prospective, nested case-control study. During the years
      1984-1989, 24-h urines were collected from 1956 men in the Kuopio Ischaemic Heart
      Disease (KIHD) Risk Factor Study. epsilondA concentrations were measured by LC
      MS/MS in 24-h urine samples from 47 men with cancer diagnosed at follow up until
      2001 and from 31 cancer free smoking-matched control subjects. Odds ratio for
      having higher than control median epsilon dA excretion rate and cancer, estimated
      by binary logistic regression, was 0.73 (95% CI 0.29-1.80, p = 0.49). In this
      study, the urinary excretion of epsilondA provides no additional prediction of
      cancer development in males after controlling for smoking.

PMID- 15875812
TI  - Caloric restriction augments ROS defense in S. cerevisiae, by a Sir2p independent
      mechanism.
AB  - Aging is associated with increased production of reactive oxygen species (ROS)
      and oxidation-induced damage to intracellular structures and membranes. Caloric
      restriction (CR) has been demonstrated to delay aging in a variety of species.
      Although the mechanisms of CR remain to be clearly elucidated, reductions in
      oxidative damage have been shown to increase lifespan in several model systems.
      Contrary to the general belief that ROS production is reduced in CR, this article
      provides evidence that not only oxygen consumption but ROS production is enhanced
      in the calorie restricted condition. To understand the biological mechanism
      underlying the anti aging action of CR, the role of scavenging enzymes was
      studied. It was found that super oxide dismutase (SOD1 and SOD2), catalase and
      glutathione peroxidase (GPx) all are over expressed in CR. We further
      investigated the role of Sir2, a potential effector of CR response in the
      activation of scavenging enzymes. No marked difference was found in CR mediated
      activation of SOD and catalase in the absence of Sir2. Our results suggest that
      in CR scavenging enzymes are activated by a Sir2 independent manner.

PMID- 15875813
TI  - Exercise-induced expression of heme oxygenase-1 in human lymphocytes.
AB  - The aim of the present investigation was to determine whether an acute bout of
      exercise increases heme oxygenase-1 (HO-1) mRNA accumulation in human
      lymphocytes. Eight male subjects performed separate exercise and rest trials in a
      randomised order at least 10 days apart. In the exercise trial subjects ran for
      75-min at a speed corresponding to 70% maximal oxygen uptake, and in the resting
      trial subjects sat calmly in the laboratory for an equivalent period of time.
      Lymphocytes were harvested from blood samples taken before and after each trial.
      Total RNA was isolated and used to determine the fold-change in HO-1 mRNA
      accumulation relative to baseline values using real time reverse transcription
      polymerase chain reaction. HO-1 protein was determined by Western blotting. Six
      of the eight subjects showed an increase in HO-1 mRNA greater than two-fold after
      exercise. The median peak fold-change was 2.7 fold with one subject showing a
      particularly pronounced response (20-fold) 24 h post-exercise. In the rest trial
      the level of HO-1 mRNA did not change over the period of investigation. There was
      also an increase in HO-1 protein 2 h after exercise. These results complement an
      earlier study showing that acute exercise of a different type (half marathon)
      leads to an increase in HO-1 expression in lymphocytes.

PMID- 15875815
TI  - A manganese porphyrin suppresses oxidative stress and extends the life span of
      streptozotocin-diabetic rats.
AB  - Enhanced oxidative stress due to hyperglycemia has been implicated in diabetic
      complications and is considered a major cause of cell and tissue damage. The aim
      of the present study was to investigate whether synthetic manganese porphyrin,
      Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin (MnTM-2-PyP5+) can
      ameliorate diabetes-induced oxidative stress and affect life span of diabetic
      rats. Diabetes was induced by a single (60 mg/kg) intraperitoneal injection of
      streptozotocin in male Wistar rats. Oxidative stress was monitored by measuring
      malondialdehyde levels (MDA) in blood plasma and erythrocytes using HPLC. The
      antioxidant status was assessed by measuring the total radical-trapping potential
      (TRAP) of blood plasma. Life span of the animals was used as an indication of the
      overall effect of MnTM-2-PyP5+. MnTM-2-PyP5+ was administered subcutaneously at 1
      mg/kg for the duration of the experiment, five times/week followed by one week of
      rest. Diabetes increased plasma and erythrocyte levels of MDA and decreased TRAP.
      MnTM-2-PyP5+ had no effect on blood glucose and glycosylated hemoglobin, but
      significantly increased TRAP and lowered MDA. This Mn porphyrin decreased
      mortality and markedly extended the life span of the diabetic animals. MnTM-2
      PyP5+ suppressed diabetes-induced oxidative stress, which presumably accounts for
      its beneficial effect on the life span of the diabetic rats. The results indicate
      that Mn(III) N-alkylpyridylporphyrins can be used as potent therapeutic agents in
      diabetes.

PMID- 15875814
TI  - Evaluation of the mechanisms involved in leucine-induced oxidative damage in
      cerebral cortex of young rats.
AB  - Maple syrup urine disease (MSUD) is a metabolic disorder caused by the deficiency
      of the activity of the mitochondrial enzyme complex branched-chain L-2-keto acid
      dehydrogenase. The metabolic block results in tissue and body fluid accumulation
      of the branched-chain amino acids leucine (Leu), isoleucine and valine, as well
      as of their respective alpha-keto acids. Neurological sequelae are usually
      present in MSUD, but the pathophysiologic mechanisms of neurotoxicity are still
      poorly known. It was previously demonstrated that Leu elicits oxidative stress in
      rat brain. In the present study we investigated the possible mechanisms involved
      in Leu-induced oxidative damage. We observed a significant attenuation of Leu
      elicited increase of thiobarbituric acid-reactive substances (TBA-RS) measurement
      when cortical homogenates were incubated in the presence of the free radical
      scavengers ascorbic acid plus trolox, dithiothreitol, glutathione, and superoxide
      dismutase, suggesting a probable involvement of superoxide and hydroxyl radicals
      in this effect. In contrast, the use of Nomega-nitro-L-arginine methyl ester or
      catalase (CAT) did not affect TBA-RS values. We also demonstrated an inhibitory
      effect of Leu on the activities of the antioxidant enzymes CAT and gluthathione
      peroxidase, as well as a significant reduction in the membrane-protein thiol
      content from mitochondrial enriched preparations. Furthermore,
      dichlorofluorescein levels were increased although not significantly by Leu.
      Taken together, our present data indicate that an unbalance between free radical
      formation and inhibition of critical enzyme activities may explain the mechanisms
      involved in the Leu-induced oxidative damage.

PMID- 15875816
TI  - Oxalomalate, a competitive inhibitor of NADP+ -dependent isocitrate
      dehydrogenase, regulates lipid peroxidation-mediated apoptosis in U937 cells.
AB  - Membrane lipid peroxidation processes yield products that may react with DNA and
      proteins to cause oxidative modifications. Recently, we demonstrated that the
      control of cytosolic redox balance and the cellular defense against oxidative
      damage is one of the primary functions of cytosolic NADP+ -dependent isocitrate
      dehydrogenase (IDPc) through to supply NADPH for antioxidant systems. The
      protective role of IDPc against lipid peroxidation-mediated apoptosis in U937
      cells was investigated in control and cells pre-treated with oxlalomalate, a
      competitive inhibitor of IDPc. Upon exposure to 2,2'-azobis (2-amidinopropane)
      hydrochloride (AAPH) to U937 cells, which induces lipid peroxidation in
      membranes, the susceptibility to apoptosis was higher in oxalomalate-treated
      cells as compared to control cells. The results suggest that IDPc plays an
      important protective role in apoptosis of U937 cells induced by lipid
      peroxidation-mediated oxidative stress.

PMID- 15875817
TI  - Maternal antioxidant concentrations after uncomplicated pregnancies.
AB  - BACKGROUND: To analyse the post-partum concentrations of intra- and extra
      cellular blood antioxidants in women with uncomplicated pregnancies. METHODS:
      Whole blood and plasma thiols, plasma vitamin E and C, serum cholesterol and
      triglyceride, ferric reducing ability of plasma (FRAP) concentrations were
      compared between women delivered by caesarean section (n=17) or spontaneous
      delivery (n=10). A repeated mixed model was used for statistical analysis.
      RESULTS: The majority of whole blood thiols increased significantly in both
      groups the first days post-partum. However, within the caesarean group free
      cysteine, oxidised cysteine, homocysteine and glutathione and plasma cysteine and
      homocysteine levels dropped significantly after 24 h, while FRAP levels peaked
      significantly in this group. Plasma vitamin E levels decreased significantly in
      both groups within 24 to 48 h after delivery. Independent of the way of delivery
      whole blood and plasma thiols were significantly increased and vitamin E levels
      were significantly decreased 3 months post-partum while plasma vitamin C levels
      and FRAP were unchanged compared to ante-partum levels. DISCUSSION: Decreased
      plasma vitamin E levels shortly post-partum are associated with decreased lipid
      peroxidation. The 24 h post-partum drop of some plasma and whole blood thiols in
      the caesarean group may be due to prolonged fasting.

PMID- 15875818
TI  - Coupling of individual polyelectrolyte capsules onto patterned substrates.

PMID- 15875819
TI  - Designing a hepatocellular microenvironment with protein microarraying and
      poly(ethylene glycol) photolithography.
AB  - In this study, robotic protein printing was employed as a method for designing a
      cellular microenvironment. Protein printing proved to be an effective strategy
      for creating micropatterned co-cultures of primary rat hepatocytes and 3T3
      fibroblasts. Collagen spots (ca. 170 microm in diameter) were printed onto amino
      silane- and glutaraldehyde-modified glass slides. Groups of 15-20 hepatocytes
      attached to collagen regions in a highly selective manner forming cell clusters
      corresponding in size to the printed collagen domains. Fibroblasts, seeded onto
      the same surface, adhered and spread around arrays of hepatocyte islands creating
      a heterotypic environment. The co-cultured hepatocytes produced and maintained
      high levels of liver-specific biomarkers, albumin and urea, over the course of 2
      weeks. In addition, protein printing was combined with poly(ethylene glycol)
      photolithography to define intercellular contacts within the clusters of
      hepatocytes residing on individual collagen islands. Glass slides, treated with 3
      acryloxypropyl trichlorosilane and imprinted with 170 m diameter collagen spots,
      were micropatterned with a high-density array of 30 microm x 30 microm
      poly(ethylene glycol) (PEG) wells. As a result, discrete groups of ca. 9 PEG
      microwells became functionalized with the cell-adhesive ligand. When exposed to
      micropatterned surfaces, hepatocytes interacted exclusively with collagen
      modified regions, attaching and becoming confined at a single-cell level within
      the hydrogel wells. Micropatterning strategies proposed here will lead to greater
      insights into hepatocellular behavior and will benefit the fields of hepatic
      tissue engineering and liver biology.

PMID- 15875820
TI  - Direct STM investigation of cinchona alkaloid adsorption on Cu(III).
AB  - Scanning tunneling microscopy (STM) combined with cyclic voltammetry has been
      employed to investigate the adsorption of cinchonine on Cu(111). Similar to
      cinchonidine, cinchonine forms a long-range ordered adlayer with (4 x 4) symmetry
      on the substrate. The structural details on molecular adsorption were obtained by
      high-resolution STM images. On the basis of the previous results and obtained STM
      images, the quinoline ring is proposed to lie parallel to Cu(111) and serve as an
      anchoring group. The chiral quinuclidine moiety extends out of the surface to
      facilitate the interaction with the prochiral reactants.

PMID- 15875821
TI  - Toward large-scale integration of carbon nanotubes.

PMID- 15875823
TI  - Size-controlled synthesis of gold nanoparticles via high-temperature reduction.

PMID- 15875822
TI  - Combinatorial scanning tunneling microscopy study of Cr deposited on anatase
      TiO2(001) surface.

PMID- 15875824
TI  - Control of wettability by anion exchange on Si/SiO2 surfaces.

PMID- 15875825
TI  - Directed patterned adsorption of magnetic beads on polyelectrolyte multilayers on
      glass.

PMID- 15875826
TI  - Thixotropic organogels based on a simple N-hydroxyalkyl amide: rheological and
      aging properties.
AB  - The thixotropic properties ofthermoreversible organogels composed ofN-3
      hydroxypropyl dodecanamide and various apolar fluids have been investigated by X
      ray scattering, light microscopy, and rheo-optics experiments. This revealed that
      gel formation occurs via a precipitation process. Depending upon the cooling
      rate, large interconnected aggregates are formed and induce an elastic behavior.
      When submitted to a shear flow, these aggregates disentangled and became aligned
      in the direction of the velocity. Nevertheless, shear does not alter the
      structure of the individual aggregate and connections between the aggregates are
      quickly rebuilt due to gravity and thermal fluctuations when the applied flow is
      stopped. The alignment under flow and the reformation of the connections after
      the cessation of the shear induces the thixotropic behavior.

PMID- 15875827
TI  - Preparation of metallodielectric composite particles with multishell structure.
AB  - In this article, we demonstrated the synthesis of metallodielectric composite
      particles comprising a metal shell on a dielectric core and an outer coating of
      an insulating dielectric layer by depositing silver on silica supporting cores
      followed by coating of titania. A combination of surface reaction and surface
      seeding techniques is exploited for the formation of a complete silver shell on
      silica spheres. The additional outer coating of titania on silver shell particles
      is then performed by hydrolyzing tetra-n-butyl titanate in ethanol at room
      temperature. The morphologies of silver shells and titania coating are studied
      with electron microscopy, and their existences are confirmed with X-ray
      diffraction and energy-dispersive X-ray measurement.

PMID- 15875828
TI  - Determining partition constants of polar organic molecules between the
      oil/interfacial and water/interfacial regions in emulsions: a combined
      electrochemical and spectrometric method.
AB  - We have developed a new approach for estimating distributions of polar additives
      in opaque, surfactant based, macroemulsions based on the pseudophase model for
      homogeneous micellar and microemulsion solutions. The distribution of a polar
      additive, such as an antioxidant, AO, within emulsions is expressed in terms of
      two partition constants, one between the oil and interfacial regions, P(O)I, and
      the other between the water and interfacial regions, P(W)I. To estimate values
      for P(O)I and P(W)I requires fitting two independent data sets with two
      independent mathematical relations and solving equations simultaneously for the
      two parameters. The experimental protocols were developed for determining the
      partition constants of tertbutylhydroquinone, TBHQ, in a stirred emulsion
      composed of octane, dilute aqueous acid, and hexaethyleneglycol monododecyl
      ether, C12E6. One data set was obtained by electrochemical determination of the
      observed rate constant, k(obs), for reaction of TBHQ with an arenediazonium ion
      probe as a function of C12E6 volume fraction. The second data set was obtained by
      determining the partition constant, P(O)W, of TBHQ between octane and water in
      the absence of surfactant by UV-visible spectrometry. TBHQ is almost 30 times
      more soluble in water than octane: P(O)W = 27.5. The values of the partition
      constants in the emulsion are P(O)I = 1.84 x 10(4) and P(W)I = 6.73 x 10(2). The
      partition constants were used to estimate the fraction of TBHQ in each region;
      for example, 96% of the TBHQ is located in the interfacial region at 0.02 volume
      fraction of C12E6. Our approach is quite general and should be applicable to any
      polar organic compound that reacts with the arenediazonium ion probe in emulsions
      composed of virtually any type of oil and surfactant. Comparisons of the rate
      constants for reaction of the antioxidant in the interfacial region of the
      emulsion, which can be obtained from the electrochemical results, may lead to a
      scale of antioxidant efficiency that is independent of the distribution of the
      antioxidant in the emulsion.

PMID- 15875829
TI  - Glassy crystalline state and water sorption of alkyl maltosides.
AB  - A differential scanning calorimetric and sorption calorimetric study of two alkyl
      maltosides, C8G2 and C10G2, was performed. In the dry state, C8G2 and C10G2 do
      not form solid crystals but undergo a glass transition upon temperature change.
      The glass is partly ordered and has the same lamellar structure as the liquid
      crystals formed by the two maltosides. To reflect the presence of the glass
      transition and the structure, the terms "glassy crystals" and "glassy liquid
      crystals" can be used. A mechanism of the relaxation of the glassy crystals based
      on the results of small-angle X-ray scattering experiments is proposed.
      Experiments on water sorption showed that the glassy crystals turn into lyotropic
      liquid crystals upon sorption of water at constant temperature. This isothermal
      glass transition can be characterized by water content and change of partial
      molar enthalpy of mixing of water. A method to calculate the phase diagram liquid
      crystals-glassy liquid crystals is proposed.

PMID- 15875830
TI  - Assembly of colloidal particles by evaporation on surfaces with patterned
      hydrophobicity.
AB  - Drops containing suspended particles are placed on surfaces of patterned
      wettability created using soft lithography; the drop diameter is large compared
      to the dimensions of the patterns on the substrate. As the three-phase contact
      line of the drop recedes, spontaneous dewetting of the hydrophobic domains and
      flow into the hydrophilic domains create discrete fluid elements with peripheries
      that can mimic the underlying surface topography. Suspended particles are carried
      with the fluid into the wetted regions and deposit there as the discrete fluid
      domains evaporate. If particle volume fractions are sufficiently high, the entire
      wetted domain can be covered with colloidal crystals. At lower volume fractions,
      flow within the evaporating fluid element can direct the deposition of colloidal
      particles at the peripheries of the domains. High-resolution arrays of particles
      were obtained with a variety of features depending upon the relative size of the
      wetting regions to the particles. When the wetting region is larger than the
      particles, three-dimensional and two-dimensional arrays of ordered particles
      mimicking the shape of the wetting pattern form, depending on the particle volume
      fraction. For lower volume fractions, one-dimensional (1-D) arrays along the
      wet/non-wet boundaries form. When the particle size is similar to the height of
      fluid on the wetted domain, zero-dimensional distributions of single particles
      centered in the wet regions can form for wetted squares or 1-D distributions
      (stripes) form along the axis of striped domains. Finally, when the wetting
      region is smaller than the particle size, the particles do not deposit within the
      features but are drawn backward with the receding drop. These results indicate
      that evaporation on surfaces of patterned wetting provides a highly
      parallelizable means of tailoring the geometry of particle distributions to
      create patterned media.

PMID- 15875831
TI  - Physicochemical aspects of the liposome-wool interaction in wool dyeing.
AB  - Despite the promising application of liposomes in wool dyeing, little is known
      about the mechanism of liposome interactions with the wool fiber and dyestuffs.
      The kinetics of wool dyeing by two dyes, Acid Green 27 (hydrophobic) and Acid
      Green 25 (hydrophilic), were compared in three experimental protocols: (1)
      without liposomes, (2) in the presence of phosphatidylcholine (PC) liposomes, and
      (3) with wool previously treated with PC liposomes. Physicochemical interactions
      of liposomes with wool fibers were studied under experimental dyeing conditions
      with particular interest in the liposome affinity to the fiber surface and
      changes in the lipid composition of the wool fibers. The results obtained
      indicate that the presence of liposomes favors the retention of these two dyes in
      the dyeing bath, this effect being more pronounced in case of the hydrophobic
      dye. Furthermore, the liposome treatment is accompanied by substantial absorption
      of PC by wool fibers with simultaneous partial solubilization of their polar
      lipids (more evident at higher temperatures). This may result in structural
      modification of the cell membrane complex of wool fibers, which could account for
      a high level of the dye exhaustion observed at the end of the liposome dyeing
      process.

PMID- 15875832
TI  - Effect of the electrostatic charge on the mechanism inducing liposome
      solubilization: a kinetic study by synchrotron radiation SAXS.
AB  - The anionic surfactant sodium dodecyl sulfate (SDS) was used to induce the
      initial steps of the solubilization of liposomes. The structural transformations
      as well as the kinetics associated with this initial period were studied by means
      of time-resolved small-angle X-ray scattering (SAXS) using a synchrotron
      radiation source. Neutral and electrically charged (anionic and cationic)
      liposomes were used to investigate the effect of the electrostatic charges on the
      kinetics of these initial steps. The mechanism that induces the solubilization
      process consisted of adsorption of surfactant on the bilayers and desorption of
      mixed micelles from the liposomes surface to the aqueous medium. In all cases the
      time needed for desorption of the first mixed micelles was shorter than that for
      complete adsorption of the surfactant on the liposomes surface. The present work
      demonstrates that adsorption of the SDS molecules on negatively charged liposomes
      was slower and release of mixed micelles from the surface of these liposomes was
      faster than for neutral liposomes. In contrast, in the case of positively charged
      liposomes, the adsorption and release processes were, respectively, faster and
      slower than those for neutral vesicles.

PMID- 15875833
TI  - Depletion interactions in model microemulsions.
AB  - The effects of temperature changes and polymer addition on the behavior of
      droplet microemulsions of nonionic surfactant, water, and decane are reported and
      analyzed within polymer depletion theory. Dilution viscometry and dynamic light
      scattering were used to confirm that these microemulsions behave essentially as
      hard-sphere dispersions, providing us with an ideal reference system. Addition of
      poly(ethylene glycol) (PEG) lowers the emulsification failure boundary, where
      excess oil is expelled, which can be qualitatively understood by an analysis of
      the available volume for the polymer. Sufficient addition of PEG causes a fluid
      fluid phase separation in qualitative accord with experiments on mixtures of
      rigid colloidal hard spheres and nonadsorbing polymer. Addition of PEG or raising
      the temperature causes the collective diffusion coefficient D(C) to decrease.
      From theory, the initial linear slope of D(C) versus droplet concentration can be
      used to discriminate between attractions and repulsions. The measured D(C) data
      for the droplets in the presence of PEG are modeled using the Asakura-Oosawa
      theory of depletion. Fitting the theory to the measured D(C) data permits for
      extracting the only unknown parameter, the polymer radius of gyration.
      Quantitative agreement is found with literature data, demonstrating that polymer
      depletion occurs in the system and that the Asakura-Oosawa theory provides a
      faithful description of the phenomenon.

PMID- 15875834
TI  - Altering surface charge nonuniformity on individual colloidal particles.
AB  - Charge nonuniformity (sigmazeta) was altered on individual polystyrene latex
      particles and measured using the novel experimental technique of rotational
      electrophoresis. It has recently been shown that unaltered sulfated latices often
      have significant charge nonuniformity (sigmazeta = 100 mV) on individual
      particles. Here it is shown that anionic polyelectrolytes and surfactants reduce
      the native charge nonuniformity on negatively charged particles by 80% (sigmazeta
      = 20 mV), even while leaving the average surface charge density almost unchanged.
      Reduction of charge uniformity occurs as large domains of nonuniformity are
      minimized, giving a more random distribution of charge on individual particle
      surfaces. Targeted reduction of charge nonuniformity opens new opportunities for
      the dispersion of nanoparticles and the oriented assembly of particles.

PMID- 15875835
TI  - Glucose-sensitive inverse opal hydrogels: analysis of optical diffraction
      response.
AB  - A glucose-sensitive inverse opal hydrogel was synthesized through
      photopolymerization of 2-hydroxyethyl methacrylate and 3-acrylamidophenylboronic
      acid within the interstitial space of a dried poly(styrene) colloidal crystal
      template, followed by template removal. Charged complex formation between the
      phenylboronic acid functional group and the 1,2-cis-diol glucose resulted in
      reversible swelling of the inverse opal hydrogel, which was observed through
      shifts in the optical diffraction wavelength. The hydrogel was sensitive to
      glucose at physiological concentrations and ionic strength. The effects of
      phenylboronic acid concentration, ionic strength, and buffer pH on the
      equilibrium hydrogel swelling were also studied. The kinetics of hydrogel
      swelling was also examined, and it was found that the rate of diffraction shift
      matched well with diffusion-limited kinetics. Additionally, the diffraction
      response was compared with simulations using the scalar wave approximation and
      transfer matrix method.

PMID- 15875836
TI  - Effect of added surfactant on temperature-induced gelation of emulsions.
AB  - This paper involves an investigation of the effect of added ionic surfactant on
      the temperature-induced gelation of oil-in-water (O/W) emulsions stabilized by a
      responsive copolymer. The oil phase used in this study is 1-bromohexadecane. The
      copolymer is poly(NIPAM-co-PEGMa) (NIPAM and PEGMa are N-isopropylacrylamide and
      poly(ethylene glycol) methacrylate, respectively). The lower critical solution
      temperature for the copolymer was 39.5 degrees C. The ionic surfactant used in
      this work was sodium dodecylbenzenesulfonate (NaDBS). The critical association
      concentration for NaDBS and poly(NIPAM-co-PEGMa) was measured at 0.30 mM using
      fluorescence measurements (pyrene was the probe molecule). Gelation temperatures
      were measured for the O/W emulsions to establish the effect of added NaDBS and
      copolymer concentration (Cp) on the gelation temperature (Tgel). The strength of
      the gels was measured using dynamic oscillatory measurements. These measurements
      allowed the shear modulus of the gel at Tgel to be estimated as 100 Pa. A
      theoretical model based on transient network theory was developed that predicts
      the dependence of Tgel on Cp. The study revealed that NaDBS has two effects on
      the overall cross-link density of the emulsion gels: it contributes a source of
      cross-linking via micellar cross-links and also decreases the proportion of
      transient cross-links due to electrostatic repulsion.

PMID- 15875837
TI  - Nanostructure of open water-channel reversed micelles. I. 1H NMR spectroscopy and
      molecular modeling.
AB  - A recently proposed model for the rodlike reversed micelles of nickel(II) bis(2
      ethylhexyl)phosphate is examined in greater detail using 1H NMR spectroscopy and
      molecular modeling. 1H NMR spectra show that the solubilized water molecules are
      situated in a different environment compared with the water molecules in
      classical (AOT) reversed micelles. Geometry optimization and molecular dynamics
      simulation clearly indicate that the water molecules are not located in the
      interior core of the reversed micelles, but instead the water molecules exist in
      compartments or channels in the surface of these rodlike reversed micelles,
      thereby confirming the open water-channel model of reversed micelles. Molecular
      modeling was also employed to examine the effects of surfactant molecular
      structure, cosurfactant, solvent aromaticity, and temperature on the
      nanostructure of the reversed micellar aggregates. It is significant that
      molecular modeling provides an interpretation of the nanostructure of reversed
      micellar aggregates that is consistent with a variety of known experimental
      observations reported in the liquid/liquid extraction literature. These findings
      show that the structure of reversed micelles is much richer at the nanoscale
      level than previously recognized.

PMID- 15875838
TI  - Water-soluble terpolymer-mediated calcium carbonate crystal modification.
AB  - The structure of the polymeric substrate plays an important role in the
      nucleation of calcium carbonate crystals. In this study a synthetic water-soluble
      poly(acrylamide-co-2-acrylamido-2-methyl-1-propane sodium sufonate-co-n-vinyl
      pyrrolidone) was found to be a substrate favoring the nucleation of polymorphs of
      calcium carbonate crystals under specific experimental conditions. Morphological
      characterization of the polymorphs was done using atomic force microscopy,
      scanning electron microscopy, energy dispersive spectroscopy, FTIR analysis, and
      X-ray diffraction. If calcium carbonate is precipitated in the presence of
      terpolymer, a remarkable increase in nucleation density (number of crystals per
      unit area) was observed. Stacked crystals of rhombohedral morphology that formed
      may be due to the presence of sodium sulfonate groups on the terpolymer. However,
      in the presence of poly-L-aspartic acid, almost all crystals are hollow and have
      needlelike or plate like morphology was formed. This change in calcium carbonate
      morphology can be explained by the variation of the polymer conformation, if poly
      L-aspartic acid is present.

PMID- 15875839
TI  - Further studies on the effect of degassing on the dispersion and stability of
      surfactant-free emulsions.
AB  - Recently reported results indicate that the formation of surfactant-free, oil-in
      water emulsions can be significantly enhanced by the almost complete removal of
      dissolved gases and that the reintroduction of dissolved gases does not
      immediately destabilize the already-formed emulsions. These initial experiments
      have been repeated and extended to include a wider range of organic liquids and
      the application of light scattering to determine droplet size and distribution.
      The earlier observations have been confirmed. In addition, a systematic trend was
      found between the solubility of the oil in water and the stability (lifetime) of
      the degassed oil droplets in water. The lower the solubility, the more stable the
      emulsion, and for oils that are sparingly soluble in water such as squalane, the
      small droplets remain stable for several weeks, with buoyancy separation being
      the main cause of instability of the large droplets with time. The addition of
      electrolytes, up to molar concentrations, substantially reduces the enhancement
      of the dispersions on degassing but appears to have little effect on the
      stability of the already-formed emulsions. The reduction of pH to about 2
      significantly reduces both the enhancement of the dispersions on degassing and
      the stability of the already-formed emulsions. In contrast, the increase of pH to
      about 11 hardly affects the enhancement of the dispersions on degassing or the
      stability of the already-formed emulsions. We have confirmed the importance of
      dissolved gas and its association with the electrostatic effects, but we still
      cannot provide a complete explanation for the effect of degassing on the
      hydrophobic dispersions.

PMID- 15875840
TI  - Molecular dynamic simulations of self-assembled alkylthiolate monolayers on an
      Au(III) surface.
AB  - Molecular dynamics simulations incorporating explicit gold atoms in the
      simulations have been carried out for alkanethiol self-assembled monolayers
      chemisorbed on the Au(III) surface. The structural properties of the monolayer
      are evaluated for two force fields: one in which the Au--S--C bond is fixed (FF
      I), and the other in which it is flexible (FF II). The influence of these force
      fields on the structural properties of HS(CH2)14CH3 on the structured Au surface
      is compared at different temperatures. FF I yields greater tilt angles and a
      smaller film thickness when compared with FF II. Both of the force fields predict
      that the tilt angles do not follow a monotonic decrease with temperature but show
      minima around 200 K. Simulations carried out at different chain lengths at 300 K
      reveal that FF II predicts a greater film thickness than FF I; however, the
      difference is within 1 A.

PMID- 15875841
TI  - Monitoring the transformation of colloidal crystals by styrene vapor using atomic
      force microscopy.
AB  - The stages of transformation of a colloidal crystalline film of latex spheres to
      a new periodic structure were imaged by atomic force microscopy. Colloidal
      crystalline films were prepared with 320 nm diameter poly(styrene-co-2
      hydroxyethyl methacrylate) (PSt/HEMA) spheres. The hexagonally ordered surfaces
      of the colloidal crystalline films were transformed with styrene vapor at room
      temperature to a new morphology having holes in the surface and the same
      periodicity as the original films. The surfaces of colloidal crystals and the
      transformed films have a raspberry-like texture superposed on the 320 nm
      hexagonal periodicity. Both height images and phase images reveal that the latex
      spheres shrink and the transformation proceeds by an order-disorder-order
      sequence. The final structure is an interconnected colloidal array with smaller
      polystyrene particles dispersed in a continuous PSt/HEMA matrix.

PMID- 15875842
TI  - Theoretical and experimental studies on the adsorption of aromatic compounds onto
      cellulose.
AB  - The adsorption of several aromatic compounds over microcrystalline cellulose was
      studied by molecular modeling and experimentally using gas chromatography.
      Experimental adsorption enthalpies were obtained from an equation based on
      Clausius-Clapeyron formalism and the temperature dependence of retention volume
      at infinite dilution. Four different cellulose surfaces (three crystalline (110,
      100, and 010) and one amorphous) were modeled. Overall strong agreement was
      observed between the experimental and theoretical work with 84% of the adsorbate
      cellulose systems having differences between measured and predicted values of
      less than 20%. Based on both calculated and experimental data, a morphology for
      the microcrystalline cellulose as a weighted combination of the four surfaces was
      proposed: 39% (110), 28% (100), 10% (010), and 23% amorphous. By adopting this
      distribution, differences between experimental and weighted average predicted
      adsorption energies were 10% or less for 14 out of 17 compounds; a maximum of 15%
      was observed for guaiacol. Experimental results for monosubstituted aromatic
      compounds revealed that adsorption enthalpies are related to the
      hydrophilic/hydrophobic character of the substituent groups: 3.5 kJ mol(-1) for a
      methyl group, 15.7 kJ mol(-1) for a double bond, 21.0 kJ mol(-1) for a methoxyl
      group, 22.8 kJ mol(-1) for a carbonyl group, and 27.6 kJ mol(-1) for a hydroxyl
      group. These tendencies were confirmed by modeling, except for the aldehyde
      carbonyl group, where an overestimation of 10.8 kJ mol(-1) was observed. Analysis
      of experimental and predicted adsorption enthalpies of multisubstituted aromatic
      compounds suggests that the efficiency of their interaction with cellulose
      depends on a compromise between the roughness of the cellulose surface and their
      conformational adaptability.

PMID- 15875843
TI  - In situ scanning tunneling microscopy of molecular assemblies of cobalt(II)- and
      copper(II)-coordinated tetraphenyl porphine and phthalocyanine on Au(100).
AB  - Molecules of copper(II) and cobalt(II) 5,10,15,20-tetraphenyl-21H,23H-porphine
      (CuTPP and CoTPP) and cobalt(II) phthalocyanine (CoPc) are spontaneously adsorbed
      onto reconstructed Au(100) substrate from a benzene solution containing each
      individual complex. In situ scanning tunneling microscopy (STM) was used to
      examine the real-space arrangement and the internal molecular structure of each
      of the individual molecules in 0.1 M HClO4 under potential control. The
      adsorption of CuTPP and CoTPP produced the same highly ordered square array with
      an intermolecular spacing of 1.44 nm on a reconstructed Au(100) surface. These
      molecular superlattices and the underlying reconstructed Au(100) predominated
      between 0 and 0.9 V, but lifting of the reconstructed Au(100) surface and
      elimination of the ordered adlayers occurred at more positive potentials.
      Molecular resolution STM revealed propeller-shaped admolecule with its center
      imaged as a protrusion for Co(II) and a depression for Cu(II). In contrast, the
      spontaneous adsorption of CoPc molecules resulted in a rapid phase transition
      from the reconstructed Au(100) surface to the (1 x 1) phase, coupled with the
      production of locally ordered, square-shaped arrays with an intermolecular
      distance of 1.65 nm. This molecular adlayer and the Au(100)-(1 x 1) remained
      unchanged when the potential was modulated between 0 and 1.0 V. These results
      indicate that the subtle variation in the molecular structure of adsorbate
      influenced not only its spatial arrangement but also the structure of the
      underlying Au(100) substrate.

PMID- 15875844
TI  - Autophobic dewetting of Z-tetraol perfluoropolyether lubricant films on the
      amorphous nitrogenated carbon surface.
AB  - The thermodynamic stability of thin films of the perfluoropolyether (PFPE) Z
      Tetraol, as a function of molecular weight, on amorphous nitrogenated carbon,
      CNx, is investigated. An optical surface analyzer is used to image the autophobic
      dewetting of the Z-Tetraol films. Film dewetting results when the PFPE film
      thickness applied to the CNx surface exceeds a critical value. This critical
      dewetting thickness is identified as the monolayer thickness of the adsorbed PFPE
      film via measurements of the changes in the surface energy as a function of
      lubricant film thickness. The observed dewetting coincides with the film
      thickness at which the disjoining pressure goes to zero. The critical dewetting
      thickness is dependent on the PFPE molecular weight.

PMID- 15875845
TI  - Formation of weak polyelectrolyte multilayers studied by spin labeling.
AB  - Multilayers of alternately adsorbing poly(allylamine) (PAH) and poly(acrylic
      acid) (PAA) of opposite charges on silica have been studied by the spin labeling
      technique, as a function of pH. The two polyelectrolytes have been labeled
      independently by a nitroxide free radical. Its electron paramagnetic resonance
      spectrum is mainly sensitive to the local Brownian motion and shows lines typical
      of two different environments, namely, loops protruding in solution with a fast
      motion and trains adsorbed on the solid with a hindered motion. These two parts
      have been evaluated for each of the polymer layers separately, and the thickness
      of the coatings has been described more precisely by characterizing the four
      contributions existing, for example, for a bilayer. Complexation is demonstrated
      by the loss of loops and tails belonging to the first polyelectrolyte. The
      overall picture emerging from the data is explained in terms of compensation of
      charges and entropy of confinement.

PMID- 15875846
TI  - Relaxation behaviors of monolayers of octadecylamine and stearic acid at the
      air/water interface.
AB  - This study investigated the relaxation behaviors of octadecylamine (ODA), stearic
      acid (SA), and SA/ODA mixed monolayers at the air/water interface. Area
      relaxations of monolayers at constant surface pressure were studied by a
      nucleation and growth mechanism and by direct observation using a Brewster angle
      microscope (BAM). The results showed that ODA and SA monolayers exhibit different
      characteristics in the area loss and in the BAM morphology. In the initial
      relaxation stage, SA monolayer illustrates a more stable characteristic than ODA.
      But at the later stage, the area loss of SA monolayer increases more quickly than
      that for ODA due to significant nucleation and growth of 3D aggregates. The BAM
      results demonstrated that 3D aggregates of large scale domains are likely to form
      on a SA monolayer even when the area loss is insignificant. On the contrary, only
      dotlike aggregates of low density were found on the ODA monolayer when relaxation
      is carried out at higher surface pressure. The relaxation behavior of SA
      monolayer can be described by the Vollhardt model. However, the relaxation of ODA
      monolayer does not follow the nucleation model described by Vollhard but can
      reasonably be attributed to the effect of dissolution. For the SA/ODA mixed
      monolayers, the relaxation behaviors in the initial and final stages follow
      different mechanisms, which is attributed to the formation of distinct phases as
      observed from the BAM. This result also implied that SA and ODA are not
      completely miscible to be a homogeneous phase. Phases of various compositions
      were formed in the mixed monolayers, and thus, the relaxation mechanism was
      shifted during the relaxation process as dominated by different relaxation
      behaviors of various phases.

PMID- 15875847
TI  - Light-excited superhydrophilicity of amorphous TiO2 thin films deposited in an
      aqueous peroxotitanate solution.
AB  - We report on the photoinduced superhydrophilicity of the surface of amorphous
      TiO2. Amorphous TiO2 thin films were prepared on self-assembled monolayers by the
      peroxotitanate-complex deposition (PCD) and liquid-phase deposition (LPD)
      methods. The surface morphology and topography were characterized in detail. The
      contact angles were 34 degrees and 66 degrees for the as-deposited thin films
      through the PCD and LPD methods, respectively, which slowly increased to about 70
      degrees and 73 degrees after being stored in air. After irradiation by UV light,
      the contact angle vanished and the surface exhibited superhydrophilicity. The
      superhydrophilicity and hydrophobicity could be switched by alternatively
      exposing the surface to UV light and drying in an atmosphere filled with organic
      gases. Although the oxidation of the contamination on the surface has effects on
      the increase in hydrophilicity, the X-ray photoelectron spectroscopy results
      suggested that the superhydrophilicity was also related to the transformation of
      the Ti-OH groups to groups that have dangling bonds. This paper indicates that an
      amorphous TiO2 thin film does not need to be heated to obtain
      superhydrophilicity; such a self-cleaning surface can be achieved at room
      temperature by our newly developed environmentally friendly method.

PMID- 15875848
TI  - Characterization of distance-dependent damping in tapping-mode atomic force
      microscopy force measurements in liquid.
AB  - We have used a spectral analysis method to characterize changes in the local
      damping coefficient for an acoustically driven cantilever as it approaches a hard
      surface in liquid. We show a significant distance dependence of the damping
      coefficient (and associated quality factor) that must be accounted for to achieve
      successful theoretical reproduction of experimental tapping-mode force curves. We
      model the cantilever dynamics using a forced damped harmonic oscillator model and
      solve the equation of motion using the method of finite differences. Experiments
      in solutions of differing viscosities show that bulk viscous damping is not the
      source of the system dissipation, while simulations of the cantilever dynamics
      including adhesion hysteresis also eliminate this as the origin of the
      dissipation. We conclude that frictional dissipation that occurs with the
      intermittent contact is the likely source of dissipation in the system. Our
      results identify a semiquantitative means of interpreting tapping-mode force
      curves on nondeformable surfaces in liquid.

PMID- 15875849
TI  - Organized self-assembled monolayers from organosilanes containing rigid pi
      conjugated aromatic segments.
AB  - The morphology of surfaces modified by pi-conjugated arylsilanes depends on
      various parameters such as the nature and the number of the hydrolyzable
      functions or the length of the aromatic segment. The grafting of
      phenyltrichlorosilane and phenyltrimethoxysilane leads to multilayers even when
      the reactions are carried out at 0 degrees C, the films obtained from
      phenyltrichlorosilane being much thicker than the one obtained from
      phenyltrimethoxysilane. A submonolayer is obtained using phenyltriethoxysilane.
      Whereas the trifunctional phenyltrichlorosilane forms an inhomogeneous
      multilayer, the difunctional phenyldichlorosilane (PhSiHCl2) and the
      monofunctional phenylchlorosilane (PhSiH2Cl) (the SiH bond is not reactive under
      these experimental conditions) deposit as dense homogeneous monolayers. For these
      two phenylchlorosilanes, the surface analytical data are similar except for
      contact angle measurements, which can be explained by a different orientation of
      the phenyl group at the surface. Concerning the influence of the length of the
      aromatic segment on the quality of the film, styryltrimethoxysilane and
      methylstilbenyltrimethoxysilane lead to dense monolayers indicating that adding a
      short group such as the vinyl group is sufficient to induce an organization
      between aromatic groups and to achieve a dense monolayer.

PMID- 15875850
TI  - Using stable and unstable profiles to deduce deformation limits of the air-water
      interface.
AB  - The shape of the air-water interface deformed by a van der Waals stress induced
      by a paraboloid shaped solid body is addressed and discussed. Emphasis is placed
      on the existence limit of solutions to the governing Euler-Lagrange equation for
      the equilibrium shape. Two legitimate solutions, one stable and one unstable, are
      found to converge at the existence limit, giving a numerical criterion for
      establishing critical physical conditions guaranteeing absolute stability.
      Insight is aided by a study of an analogous mechanical problem that exhibits very
      similar properties. Among numerical data produced are critical lower height
      limits of the paraboloid to the air-water surface and associated peak deformation
      heights and their dependencies on physical parameters. Of further interest to
      experimentalists in the surface force field are the variations in peak
      deformation height and total surface force on the solid as a function of position
      of the paraboloid, paraboloid geometry, and strength of the van der Waals stress.

PMID- 15875851
TI  - Coadsorption and surface forces for selective surfaces in contact with aqueous
      mixtures of oppositely charged surfactants and low charge density
      polyelectrolytes.
AB  - The coadsorption of a positively charged polyelectrolyte (with 10% of the
      segments carrying a permanent positive charge, AM-MAPTAC-10) and an anionic
      surfactant (sodium dodecyl sulfate, SDS) on silica and glass surfaces has been
      investigated using optical reflectometry and a noninterferometric surface force
      technique. This is a selective coadsorption system in the sense that the
      polyelectrolyte does adsorb to the surface in the absence of surfactant, whereas
      the surfactant does not adsorb in the absence ofpolyelectrolyte. It is found that
      the total adsorbed amount goes through a maximum when the SDS concentration is
      increased. Maximum adsorption is found when the polyelectrolyte/surfactant
      complexes formed in bulk solution are close to the charge neutralization point.
      Some adsorption does occur also when SDS is present in significant excess. The
      force measured between AM-MAPTAC-10-coated surfaces on approach in the absence of
      SDS is dominated at long range by an electrostatic double-layer force. Yet,
      layers formed by coadsorption from solutions containing both polyelectrolyte and
      surfactant generate long-range forces of an electrosteric nature. On separation,
      adhesive interactions are found only when the adsorbed amount is low, i.e., in
      the absence of SDS and in a large excess of SDS. The final state of the adsorbed
      layer is found to be nonhysteretic, i.e., independent of the history of the
      system. The conditions for formation of long-lived trapped adsorption states from
      mixed polymer-surfactant solutions are discussed.

PMID- 15875852
TI  - Direct method for surface silyl functionalization of mesoporous silica.
AB  - A direct method of surface silyl modification and simultaneous surfactant removal
      of mesoporous silica is investigated in its physicochemical details. Twelve
      different silanes of various functionalities are studied. The method employs an
      alcohol solution of silanes to allow the simultaneous surfactant/silyl exchange
      process, which results in a more uniform monolayer coverage of the surface and a
      higher amount of surface attachments of silane. We vary the solution
      concentration of silanes to study the effect on loadings. It is found that the
      variation of the surface loading of the silyl group follows a Langmuir adsorption
      model closely. The method gives one a well-controlled monolayer coverage of the
      surface. The loadings are determined by the exchange equilibrium. Fittings of the
      loading data to Langmuir adsorption isotherms give one the adsorption equilibrium
      constants and maximum surface loadings. We categorize the silanes into three
      different groups according to the values of the equilibrium constants and discuss
      them with respect to molecular structures. We also report on the extensive
      characterizations of the surface-functionalized mesoporous materials, such as
      nitrogen adsorptions, X-ray diffraction, 29Si magic-angle spinning NMR, 13C magic
      angle spinning NMR, and IR spectroscopy. The method provides one with a
      convenient and highly controllable approach to the surface functionalization of
      mesoporous silica.

PMID- 15875853
TI  - Comparison between CH3(CH2)15SH and CF3(CF2)3(CH2)11SH monolayers on
      electrodeposited silver.
AB  - In this paper, two monolayers self-assembled on a silver substrate are compared:
      a monolayer of n-hexadecanethiol and a monolayer of n-11
      perfluorobutylundecanethiol. The protecting properties of both monolayers have
      been extensively studied by X-ray photoelectron spectroscopy, contact angle,
      polarization modulation infrared reflection absorption spectroscopy, conventional
      electrochemical techniques (polarization curves and electrochemical impedance
      spectroscopy), and scanning vibrating electrode technique. Both monolayers were
      successfully self-assembled but organization is slightly different, the
      fluorinated segment introduces small disorganization. Nevertheless, good
      homogeneous corrosion protection is observed for each monolayer.

PMID- 15875854
TI  - The effects of network structure on the resistance of silane coupling agent
      layers to water-assisted crack growth.
AB  - Silane adhesion promoters are commonly used to improve the adhesion, durability,
      and corrosion resistance of polymer-oxide interfaces. The current study
      investigates a model interface consisting of the natural oxide of(100) Si and an
      epoxy cured from diglycidyl ether ofbisphenol A (DGEBA) and triethylenetetraamine
      (TETA). The thickness of (3-glycidoxypropyl)trimethoxysilane (GPS) films placed
      between the two materials provided the structural variable. Five surface
      treatments were investigated: a bare interface, a rough monolayer film, a smooth
      monolayer film, a 5 nm thick film, and a 10 nm thick film. Previous neutron
      reflection experiments revealed large extension ratios (>2) when the 5 and 10 nm
      thick GPS films were exposed to deuterated nitrobenzene vapor. Despite the larger
      extension ratio for the 5 nm thick film, the epoxy/Si fracture energy (Gc) was
      equal to that of the 10 nm thick film under ambient conditions. Even the smooth
      monolayer exhibited the same Gc. Only when the monolayer included a significant
      number of agglomerates did the Gc drop to levels closer to that of the bare
      interface. When immersed in water at room temperature for 1 week, the threshold
      energy release rate (Gth) was nearly equal to Gc for the smooth monolayer, 5 nm
      thick film, and 10 nm thick film. While the Gth for all three films decreased
      with increasing water temperature, the Gth of the smooth monolayer decreased more
      rapidly. The bare interface was similarly sensitive to temperature; however, the
      Gth of the rough monolayer did not change significantly as the temperature was
      raised. Despite the influence of pH on hydrolysis, the Gth was insensitive to the
      pH of the water for all surface treatments.

PMID- 15875855
TI  - AFM observation of cation complexation of dibenzocrown ethers adsorbed on highly
      oriented pyrolytic graphite.
AB  - The cation complexation behavior of dibenzocrown ethers adsorbed on highly
      oriented pyrolytic graphite substrates was investigated by means of atomic force
      microscopy using probe tips modified chemically with ammonium ion by silane
      coupling. The specific adhesion force based on the intermolecular force between
      dibenzocrown ether and ammonium ion was observed via force curve measurements in
      ethanol at the interface between the substrate and tip. The observed specific
      force decreased in the presence of the alkali metal ion in solution, indicating
      that the cation in solution interferes with the complexation of the crown ethers
      adsorbed on the substrate with the ammonium ion immobilized on the tip. The
      blocking effect of metal ions in solution on the observed force depended on the
      sizes of both the blocking cation and crown ether ring, suggesting that the
      surface-adsorbed dibenzocrown ethers possess a selective cation-complexing
      ability similar to that in their bulk state and that the adhesion force
      measurements using cation-modified tips allow evaluation of the cation-complexing
      ability of crown ethers under cation-competitive conditions.

PMID- 15875856
TI  - Atomic force microscopy study of the adsorption and electrostatic self
      organization of poly(amidoamine) dendrimers on mica.
AB  - The adsorption behavior of poly(amidoamine) dendrimers to mica surfaces was
      investigated as a function of ionic strength and pH. The conformation and lateral
      distribution of the adsorbed dendrimers of generations G8 and G10 were obtained
      ex situ by tapping mode atomic force microscopy (AFM). The deposition kinetics of
      the dendrimers was found to follow a diffusion-limited process. Fractional
      surface coverage and pair correlation functions of the adsorbed dendrimers were
      obtained from the AFM images. The data are interpreted in terms of the random
      sequential adsorption (RSA) model, where electrostatic repulsion due to
      overlapping double layers is considered. Although the general trends typical for
      an RSA-determined process are well-reproduced, quantitative agreement is lacking
      at low ionic strengths.

PMID- 15875857
TI  - Thickness-dependent molecular chain and lamellar crystal orientation in ultrathin
      poly(di-n-hexylsilane) films.
AB  - The molecular chain and lamellar crystal orientation in ultrathin films
      (thickness < 100 nm) of poly-(di-n-hexylsilane) (PDHS) on silicon wafer
      substrates have been investigated by using transmission electronic microscopy,
      wide-angle X-ray diffraction, atomic force microscopy, and UV absorption
      spectroscopy. PDHS showed a film thickness-dependent molecular chain and lamellar
      crystal orientation. Lamellar crystals grew preferentially in flat-on orientation
      in the monolayer ultrathin films of PDHS, i.e., the silicon backbones were
      oriented along the surface-normal direction. By contrast, the orientation of
      lamellar crystals was preferentially edge-on in ultrathin films thicker than ca.
      13 nm, i.e., the silicon backbones were oriented parallel to the substrate
      surface. We interpret the different orientations of molecular chain and lamellar
      crystal as due to the reduction of the entropy of the polymer chain near the
      substrate surface and the particularity of the crystallographic (001) plane of
      flat-on lamellae, respectively. A remarkable influence of the orientations of the
      silicon backbone on the UV absorption of these PDHS ultrathin films was observed
      due to the one-dimensional nature of sigma-electrons delocalized along the
      silicon backbone. With the silicon backbones perpendicular or parallel to the
      surface of the substrate, the UV absorbance increased or decreased with an
      increase of the angle between the incident UV beam direction and direction normal
      to the thin film, respectively.

PMID- 15875858
TI  - Fabrication of self-assembled monolayers (SAMs) and inorganic micropattern on
      flexible polymer substrate.
AB  - By grafting (aminopropyl)triethoxysilane (APTES) as the buffer layer on
      poly(ethylene terephthalate) (PET) surface, the SAMs ofoctadecyltrichlorosilane
      (OTS), phenyltrichlorosilane (PTCS), vinyltrichlorosilane (VTCS), andp
      tolyltrichlorosilane (TTCS) were fabricated on the flexible polymer substrate.
      The properties of SAMs were accurately controlled by adjusting the immersing time
      of substrates in the solutions and the concentration of the solutions. The SAMs
      acted as templates, and TiO2 micropattern was successfully deposited on OTS,
      TTCS, and PTCS SAMs.

PMID- 15875859
TI  - Monolayer behavior of 1,2-dipalmitoylgalloylglycerol, a synthetic lipid with
      strong cohesive properties.
AB  - Monolayers of 1,2-dipalmitoylgalloylglycerol (DPGG) were investigated at the air
      water interface. The monolayers exhibit high rigidity which leads to the
      formation of surface tension gradients in the film. Transfer to solid substrate
      yields homogeneous Langmuir-Blodgett films with low surface roughness. Large
      numbers of aggregates were observed by Brewster angle microscopy and imaging
      ellipsometry at relatively high molecular areas. At all pressures, the DPGG
      molecules adopt conformations corresponding to low tilt angles. Constant area
      measurements result in a pressure increase as the film rearranges to maximize the
      intermolecular interactions. An optimal intermolecular distance required for the
      formation of a hydrogen-bond network between headgroups is proposed to explain
      the observed, highly cohesive monolayer behavior.

PMID- 15875860
TI  - Silver halide colloid precursors for the synthesis of monolayer-protected
      clusters.
AB  - A new method for the synthesis of monolayer-protected silver clusters (MPCs)
      based on the two-phase reduction of a stable negatively charged silver bromide
      sol is described. Phase transfer of the colloid to toluene is accomplished using
      tetra-n-octylammonium bromide as the phase transfer reagent. The advantage of
      this synthesis is to uncouple the formation of the silver halide colloid from its
      transfer and reduction in the organic phase, thus allowing control over each
      reaction step. The silver colloid in toluene was reduced with aqueous borohydride
      in the presence of 4-bromobenzenethiol as the passivating agent. The UV-visible
      absorption spectra indicate the intermediate formation of Ag(core)AgBr(shell)
      clusters during reduction. The resulting MPCs have been characterized by optical
      and transmission electron microscopy, energy-dispersive X-ray analysis,
      thermogravimetry, and UV-vis absorption spectroscopy. The formation of spiral
      cracks in the nanoparticulate agglomerates on solvent evaporation was observed.
      The spectra of thin films obtained by solvent evaporation have been analyzed
      using an effective medium theory.

PMID- 15875861
TI  - Molecular weight and polydispersity estimation of adsorbing polymer brushes by
      atomic force microscopy.
AB  - We have estimated the molecular weight, Mn, and polydispersity, PDI, of densely
      grafted poly(N-isopropylacrylamide) (PNIPAM) brushes using a novel atomic force
      microscopy (AFM) approach. When compression of a polymer brush induced adsorption
      of multiple chains to an AFM tip, the resulting decompression force profile
      exhibited a maximum attractive force at a separation, Lm, that decayed to zero
      with increasing tip-sample separation. We have found that the separation Lm
      approximates the average contour length, Lc, determined by gel permeation
      chromatography (GPC). The detection of a decaying attractive force at separations
      larger than Lc suggests that chains of above average length sequentially break
      free from the tip as they are stretched away from the grafting surface. The shape
      of the decompression profile in this region approximately paralleled the
      cumulative weight fraction of the grafted chains determined by GPC. The fraction
      of chains of a given molecular weight determined from a single force curve fit a
      log-normal distribution, having a standard deviation that provided an estimate of
      the PDI. We have characterized two PNIPAM brushes by this AFM technique as well
      as by GPC coupled to a multiangle laser light-scattering detector (MALLS). The
      values obtained by AFM-(1) Mn,AFM = (3.8+/-0.5) x 10(4), PDI,(AFM) = 1.3+/-0.1
      and (2) Mn,AFM = (9.4+/-1.4) x 10(4), PDI,(AFM) = 1.3+/-0.1-agreed quite well
      with the corresponding GPC/MALLS values of (1) Mn,GPC = 4.77 x 10(4), PDI,GPC =
      1.33 and (2) Mn,GPC = 9.49 x 10(4), PDI = 1.35. This technique requires only a
      single force curve to obtain a statistical distribution of contour lengths and
      provides a novel method for estimating the Mn and PDI of appropriate uniformly
      grafted dense polymer layers.

PMID- 15875862
TI  - Creating effective refractive index gradients within polyelectrolyte multilayer
      films: molecularly assembled rugate filters.
AB  - We demonstrate the use of aqueous-based layer-by-layer (LbL) processing and in
      situ nanoreactor chemistry for creating polyelectrolyte multilayer (PEM)
      nanocomposites in which the concentration of a nanoparticle species is modulated
      throughout the depth of the film in a complex way. Using the in situ growth of
      silver nanoparticles to selectively increase the refractive index of precisely
      defined regions of the PEM film, we have produced a digitized rugate filter, a
      special type of dielectric mirror possessing many thin layers that approximate a
      continuous, periodic refractive index profile. The design of the digital rugate
      from an initial smooth index profile was aided by a computer, and construction of
      the device was accomplished entirely by automated means. Poly(allylamine
      hydrochloride) (PAH) and poly(acrylic acid) (PAA) bilayer regions within the film
      supported subsequent nanoreactor chemistry and created the high refractive index
      regions of the film, while PAH and poly(styrenesulfonate) (PSS) bilayer regions
      remained unmodified and served as the low index regions. Spectroscopic results
      obtained from the assembled device confirm the presence of a reflection band that
      grows in amplitude with increasing silver incorporation, reaching a peak
      reflectance of 75% after five silver loading and exchange cycles. The rugate
      structure suppresses reflection sidebands, features common to Bragg reflectors
      and simpler dielectric mirror designs. Cross-sectional TEM reveals nanoscale
      control of the size and location of silver-containing domains within the PEM
      film. The ability of this method to control the placement of nanoparticles within
      PEMs enables the inexpensive, easy production of conformable optical coatings
      with tunable properties. In addition, these nanocomposite films may have
      applications in a number of other fields where precise control of effective
      gradients in physical properties throughout thin films has been shown to affect
      the overall performance in a desirable way.

PMID- 15875863
TI  - Hydration of black foam films made of amphiphilic cyclodextrins.
AB  - We investigate the interfacial behavior of a new type of amphiphilic cyclic
      oligosaccharide obtained by grafting a phospholipid onto a methylated
      cyclodextrin. These compounds are able to form stable black foam films, the
      structure of which can be determined using X-ray reflectivity. These films
      consist of a highly hydrated bilayer of modified cyclodextrins which are
      remarkably thick due to their abundant hydration core. In the present paper, we
      explore the influence of cyclodextrin hydration on the film structure. The
      hydration rate of the films is tuned by changing the cyclodextrin methylation, by
      binding the modified cyclodextrins to various molecules (complex formation) and
      by exposing the films to IR radiation. In addition, we show that the gas
      permeability of these phospholipidyl-cyclodextrin films is governed by their
      central layer of bound water, which is an efficient barrier against gas
      permeation.

PMID- 15875864
TI  - Well-ordered self-assembled monolayers created via vapor-phase reactions on a
      monolayer template.
AB  - The reaction of vapor-phase alkyl isocyanates (O=C=N-(CH2)n-1CH3) with OH
      terminated alkanethiol template monolayers on Au produces well-organized self
      assembled monolayers, containing intrachain carbamate linkages
      (Au/S(CH2)16O(C=O)NH(CH2)n-1CH3, where n = 1-8, 11, and 12). X-ray photoelectron
      spectroscopy, contact angle goniometry, and reflection absorption infrared
      spectroscopy suggest that the template surface completely reacts with the
      isocyanates yielding a monolayer that contains an interchain hydrogen-bonded
      carbamate network. Spectroscopic data indicates that the alkyl underlayer remains
      well ordered following reaction with the isocyanates. The order of the overlayer
      and the hydrogen-bonding interactions between adjacent chains increase as a
      function of the alkyl isocyanate chain length, n. The overlayer appears to be
      well ordered for n > or = 5.

PMID- 15875865
TI  - Reactive coupling of 4-vinylaniline with hydrogen-terminated Si(100) surfaces for
      electroless metal and "synthetic metal" deposition.
AB  - Pristine and resist-patterned Si(100) substrates were etched by aqueous HF to
      produce hydrogen-terminated silicon (H-Si(100)) surfaces. The H-Si(100) surface
      was then subjected to UV-induced reactive coupling of 4-vinylaniline (VAn) to
      produce the VAn monolayer-modified silicon (VAn-Si) surface. The VAn-Si surface
      was first functionalized with a "synthetic metal" by oxidative graft
      polymerization of aniline with the aniline moieties of the coupled VAn molecules.
      The composition and topography of the VAn-Si and polyaniline (PAn)-grafted VAn-Si
      (PAn-VAn-Si) surfaces were characterized by X-ray photoelectron spectroscopy and
      atomic force microscopy, respectively. The doping-undoping (protonation
      deprotonation) and redox-coupling (metal reduction) behavior, as well as the
      electrical conductivity, of the surface-grafted PAn were found to be similar to
      those of the aniline homopolymer. The VAn-Si surface was also funtionalized by
      the electroless plating of copper. Not only did the VAn layer provide
      chemisorption sites for the palladium catalyst, in the absence of prior
      sensitization by SnCl2, during the electroless plating process, it also served as
      an adhesion promotion layer and a low-temperature diffusion barrier for the
      electrolessly deposited copper. Finally, micropatterning of the grafted PAn and
      of the electrolessly deposited copper were demonstrated on the resist-patterned
      VAn-Si surfaces.

PMID- 15875866
TI  - Interaction of apo cytochrome c with sulfonated polystyrene nanoparticles.
AB  - Stable nanoparticle dispersion in aqueous solutions was obtained with partially
      sulfonated polystyrene. The hydrophobic association of the backbone chains and
      phenyl groups is balanced by the electrostatic repulsion of the sulfonate groups
      on the particle surface. The size distribution of the sulfonated polystyrene
      particles in relation to concentration, degree of sulfonation and chain length,
      and pH was characterized by dynamic laser light-scattering. The structure and
      morphology of the particles were characterized with fluorescence and atom force
      microscopy. Highly sulfonated polystyrene particles can form large complex
      particles with positively charged protein, apo cytochrome c. Dynamic laser light
      scattering and atom force microscopy studies show that the size and distribution
      of the complex particles depend on the relative amount of apo cytochrome c and
      sulfonated polystyrene. When sulfonated polystyrene is in excess, apo cytochrome
      c interacts with sulfonated polystyrene particles forming stable complexes and
      excessive sulfonated polystyrene particles bind to the periphery of the complexes
      preventing them from further aggregation. When apo cytochrome c is in excess, apo
      cytochrome c links the complexes forming much larger particles. Fluorescence
      study demonstrates that the hydrophobicity/hydrophility of the complex particles
      is relative to the ratio of apo cytochrome c and sulfonated polystyrene, degree
      of sulfonation, and pH. Apo cytochrome c not only can neutralize the negative
      charges on the surface of sulfonated polystyrene particles, but may also insert
      into the cores disrupting the original structure of sulfonated polystyrene
      particles.

PMID- 15875867
TI  - Adsorption of lipid-functionalized poly(ethylene glycol) to gold surfaces as a
      cushion for polymer-supported lipid bilayers.
AB  - Inclusion of a polymer cushion between a lipid bilayer membrane and a solid
      surface has been suggested as a means to provide a soft, deformable layer that
      will allow for transmembrane protein insertion and mobility. In this study, the
      properties of a heterofunctional, telechelic PEG lipopolymer (1,2-distearoyl-sn
      glycero-3-phosphoethanolamine-N-poly(ethylene glycol)-2000-N- [3-(2
      (pyridyldithio)propionate]) (DSPE-PEG-PDP) adsorbed from ethanol and water
      solutions onto gold surfaces were studied using a variety of surface-sensitive
      techniques. X-ray photoelectron spectroscopy showed that the PEG molecules are
      tethered to the gold surface via thiolate bonds. When adsorbed from water,
      ethanol, or their mixtures, reflection-absorption infrared spectroscopy showed
      that amorphous PEG layers with disordered DSPE alkyl chains were formed,
      independent of adsorption time or solution concentration. On the basis of
      advancing and receding water and hexadecane contact angles on the lipopolymer
      films, the DSPE lipid groups appear to segregate from the PEG layer and become
      exposed at the surface of the polymer films. Swelling observed in surface plasmon
      resonance experiments and the large contact angle hysteresis observed indicate
      that highly swellable, mobile films capable of molecular rearrangements are
      formed. The self-assembling and amorphous properties of these PEG layers make
      them ideal candidates as polymer cushions for polymer-supported lipid bilayers.
      The DSPE surface concentration can be controlled, to a limited degree, by varying
      the adsorption time of DSPE-PEG-PDP from ethanol. A more effective strategy is to
      coadsorb DSPE-PEG-PDP with a non-lipid-functionalized PEG-PDP from an
      ethanol/water mixture, which allows the PEG thickness and density to remain
      constant while decreasing the density of DSPE groups.

PMID- 15875868
TI  - Synthesis and characterization of active ester-functionalized polypyrrole-silica
      nanoparticles: application to the covalent attachment of proteins.
AB  - Novel ester-functionalized polypyrrole-silica nanocomposite particles were
      prepared by oxidative copolymerization of pyrrole and N-succinimidyl ester
      pyrrole (50/50% initial concentrations), using FeCl3 in the presence of ultrafine
      silica nanoparticles (20 nm diameter). The N-succinimidyl ester pyrrole monomer
      was prepared in aqueous solution using 1-(2-carboxyethylpyrrole) and N
      hydroxysuccinimide in the presence of 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide. The resulting nanocomposites (N-succinimidyl ester polypyrrole
      silica) are raspberry-shaped agglomerates of silica sol particles "glued"
      together by the insoluble poly(pyrrole-co-N-succinimidyl pyrrole). The N
      succinimidyl ester polypyrrole-silica particles were characterized in terms of
      their size, density, copolymer content, and polydispersity. Scanning electron
      microscopy and disk centrifuge sedimentometry confirmed that the nanocomposite
      particles had narrow size distributions. X-ray photoelectron spectroscopy
      analysis indicated a silica-rich surface and a high surface concentration of N
      succinimidyl ester groups. These nanoparticles exhibited good long-term
      dispersion stability. The chemical stability of the ester functions in aqueous
      media after several weeks of storage was monitored by FTIR spectroscopy. The
      functionalized nanocomposites were tested as bioadsorbents of human serum albumin
      (HSA). The very high amount of immobilized HSA determined by UV-visible
      spectroscopy is believed to be due to covalent binding. Incubation of the HSA
      grafted nanocomposite with anti-HSA resulted in immediate flocculation, an
      indication that they are alternative candidates for visual diagnostic assays.

PMID- 15875869
TI  - Sequence-dependent DNA immobilization: specific versus nonspecific contributions.
AB  - We present results of the first systematic study on in situ sequence-dependent
      kinetics for short single-strand oligonucleotide surface immobilization. By
      measuring film coverage for both thiolated and nonthiolated homo-oligomers as a
      function of adsorption time, we determine the relative contribution of specific
      thiol-surface and nonspecific DNA-surface interactions to the overall mechanism
      of DNA-thiol attachment to gold. We find that sequence-dependent nonspecific
      surface interactions play a significant role in DNA-thiol immobilization,
      influencing not only the kinetics but also the extent of oligomer adsorption. For
      example, sequences that initially form strong, rapid nonspecific contacts with
      the surface hinder long-time thiol adsorption (i.e., poly(dA)-thiol). In
      contrast, sequences with nucleotides that initially bind slowly and weakly to the
      surface (i.e., poly(dT)-thiol) do not obstruct further thiol adsorption,
      resulting in higher film coverage and Langmuir immobilization kinetics. This view
      of the DNA-thiol immobilization mechanism is further supported by sequence
      dependent rinsing losses observed for thiolated DNA strands but not for analogous
      nonthiolated strands. Nonthiolated strands contact the surface strongly in a more
      horizontal orientation, whereas thiolated strands attain a more upright
      orientation that allows vertical DNA-DNA base-stacking. The results clearly
      illustrate the importance and interplay of competitive specific and nonspecific
      forces in forming DNA-thiol films. The specific coverage attained and the time
      dependence of the adsorption process depend on the prevailing sequence
      composition.

PMID- 15875870
TI  - Fibronectin adsorption onto polyelectrolyte multilayer films.
AB  - The Layer-by-layer deposition of positively and negatively charged macromolecular
      species is an ideal method for constructing thin films incorporating biological
      molecules. We investigate the adsorption of fibronectin onto polyelectrolyte
      multilayer (PEM) films using optical waveguide lightmode spectroscopy (OWLS) and
      atomic force microscopy (AFM). PEM films are formed by adsorption onto Si(Ti)O2
      from alternately introduced flowing solutions of anionic poly(sodium 4
      styrenesulfonate) (PSS) and cationic poly(allylamine hydrochloride) (PAH). Using
      OWLS, we find the initial rate and overall extent offibronectin adsorption to be
      greatest on PEM films terminated with a PAH layer. The polarizability density of
      the adsorbed protein layer, as measured by its refractive index, is virtually
      identical on both PAH- and PSS-terminated films; the higher adsorbed density on
      the PAH-terminated film is due to an adsorbed layer of roughly twice the
      thickness. The binding of monoclonal antibodies specific to the protein's cell
      binding site is considerably enhanced to fibronectin adsorbed to the PSS layer,
      indicating a more accessible adsorbed layer. With increased salt concentration,
      we find thicker PEM films but considerably thinner adsorbed fibronectin layers,
      owing to increased electrostatic screening. Using AFM, we find adsorbed
      fibronectin layers to contain clusters; these are more numerous and symmetric on
      the PSS-terminated film. By considering the electrostatic binding of a segmental
      model fibronectin molecule, we propose a picture of fibronectin adsorbed
      primarily in an end-on-oriented monolayer on a PAH-terminated film and as
      clusters plus side-on-oriented isolated molecules onto a PSS-terminated film.

PMID- 15875871
TI  - Molecular dynamics simulation of the adsorption of a fibronectin module on a
      graphite surface.
AB  - We report atomistic simulations of the adsorption of a fibronectin type I module
      on a hydrophobic graphite surface. This module comprises only beta-sheets, unlike
      the albumin fragments previously investigated by us which contained only alpha
      helices (Raffaini, G.; Ganazzoli, F. Langmuir 2003, 19, 3403-3412). As done in
      the latter case, most simulations are carried out in an effective dielectric
      medium by energy minimizations and molecular dynamics (MD). Further optimizations
      and MD runs in the explicit presence of water are also performed to assess the
      stability of the geometries found and to describe the solvation of the adsorbed
      fibronectin module. The initial adsorption is accompanied by local rearrangements
      of the strands in contact with the surface, but the overall molecular structure
      is largely preserved. Much larger rearrangements take place at longer times as
      found through the MD runs, with the molecule spreading as much as possible so as
      to maximize the surface coverage, hence the interaction energy, despite a
      significant strain energy. Energetic aspects of adsorption together with the
      concomitant size change are discussed in comparison with our previous results for
      two albumin fragments.

PMID- 15875873
TI  - Surface properties of porous carbon obtained from polystyrene sulfonic acid-based
      organic salts.
AB  - Pyrolysis ofpolysterene sulfonic acid-co-maleic acid salts at 800 degrees C
      resulted in formation of new materials consisting of porous carbon and metal
      species dispersed on the surface. After hydrochloric acid treatment, the metal
      oxides/salts were removed. Obtained materials were characterized using adsorption
      of nitrogen, thermogravimetric analysis, Raman spectroscopy, and scanning
      electron microscopy with energy dispersive analysis of X-rays. The results showed
      highly developed porous structures in the range of micro- and mesopores. The
      porous features of new materials resemble those characteristics for carbon foams.
      The differences in the porous structure are linked to the type of transition
      metal used for the modification of the initial polymer and the chelation process.
      Macro- and mesopores are spherical/cylindrical in shape, and they are likely
      formed when release of pyrolysis gases, such as CO2, NO2, SO2, H2S, and CxHy,
      occurs. Moreover, reduction of metal, its migration to the surface, and
      agglomeration contribute to development of porosity. Depending on the reactivity
      of the metal used for cation exchange (Fe, Co, or Ni) either sulfides (nickel and
      cobalt) or oxides (cobalt and iron) are formed on the carbon surface.

PMID- 15875872
TI  - Interaction of antimicrobial arginine-based cationic surfactants with liposomes
      and lipid monolayers.
AB  - The present work examines the relationship between the antimicrobial activity of
      novel arginine-based cationic surfactants and the physicochemical process
      involved in the perturbation of the cell membrane. To this end, the interaction
      of these surfactants with two biomembrane models, namely, 1,2-dipalmitoyl-sn
      glycero-3-phosphocholine (DPPC) multilamellar lipid vesicles (MLVs) and
      monolayers of DPPC, 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)]
      sodium salt (DPPG), and Escherichia coli total lipid extract, was investigated.
      For the sake of comparison, this study included two commercial antimicrobial
      agents, hexadecyltrimethylammonium bromide and chlorhexidine dihydrochloride.
      Changes in the thermotropic phase transition parameters of DPPC MLVs in the
      presence of the compounds were studied by differential scanning calorimetry
      analysis. The results show that variations in both the transition temperature
      (Tm) and the transition width at half-height of the heat absorption peak
      (deltaT1/2) were consistent with the antimicrobial activity of the compounds.
      Penetration kinetics and compression isotherm studies performed with DPPC, DPPG,
      and E. coli total lipid extract monolayers indicated that both steric hindrance
      effects and electrostatic forces explained the antimicrobial agent-lipid
      interaction. Overall, in DPPC monolayers single-chain surfactants had the highest
      penetration capacity, whereas gemini surfactants were the most active in DPPG
      systems. The compression isotherms showed an expansion of the monolayers compared
      with that of pure lipids, indicating an insertion of the compounds into the lipid
      molecules. Owing to their cationic character, they are incorporated better into
      the negatively charged DPPG than into zwitterionic DPPC lipid monolayers.

PMID- 15875874
TI  - Matrix polyelectrolyte microcapsules: new system for macromolecule encapsulation.
AB  - A new approach to fabricate polyelectrolyte microcapsules is based on exploiting
      porous inorganic microparticles of calcium carbonate. Porous CaCO3 microparticles
      (4.5-5.0 microns) were synthesized and characterized by scanning electron
      microscopy and the Brunauer-Emmett-Teller method of nitrogen
      adsorption/desorption to get a surface area of 8.8 m2/g and an average pore size
      of 35 nm. These particles were used as templates for polyelectrolyte layer-by
      layer assembly of two oppositely charged polyelectrolytes, poly(styrene
      sulfonate) and poly(allylamine hydrochloride). Calcium carbonate core dissolution
      resulted in formation ofpolyelectrolyte microcapsules with an internal matrix
      consisting of a polyelectrolyte complex. Microcapsules with an internal matrix
      were analyzed by confocal Raman spectroscopy, scanning electron microscopy, force
      microscopy, and confocal laser-scanning fluorescence microscopy. The structure
      was found to be dependent on a number of polyelectrolyte adsorption treatments.
      Capsules have a very high loading capacity for macromolecules, which can be
      incorporated into the capsules by capturing them from the surrounding medium into
      the capsules. In this paper, we investigated the loading by dextran and bovine
      serum albumin as macromolecules. The amount of entrapped macromolecules was
      determined by two independent methods and found to be up to 15 pg per
      microcapsule.

PMID- 15875875
TI  - Bimetallic (Ag)Au nanoparticles prepared by the seed growth method: two
      dimensional assembling, characterization by energy dispersive X-ray analysis, X
      ray photoelectron spectroscopy, and surface enhanced raman spectroscopy, and
      proposed mechanism of growth.
AB  - Layered core-shell bimetallic silver-gold nanoparticles were prepared by
      overdeposition of Au over Ag seeds by the seed-growth method using
      tetrachloroauric acid, with hydroxylamine hydrochloride as the reductant. The
      effects of pH, reduction rate, and seeding conditions on the morphology and
      surface plasmon extinction of the bimetallic nanoparticles were investigated.
      Nanoparticles prepared by a rapid reduction in the neutral ambient and assembled
      into two-dimensional nanoparticulate films by adsorption of 2,2'-bipyridine were
      characterized by energy-dispersive X-ray analysis, X-ray photoelectron
      spectroscopy, surface-enhanced Raman scattering spectroscopy, and transmission
      electron microscopy. The results are consistent with Ag core and Ag/Au-alloyed
      shell composition of the nanoparticles. Evidence of the presence of Ag on the
      surface of the nanoparticles, of enrichment of the Ag/Au alloy shell by Ag toward
      or at the nanoparticle surface, and of modification of the nanoparticle surface
      by adsorbed chlorides is also provided. Reduction of the size of the Ag seeds,
      alloying of Ag and Au in the shell of the nanoparticles, and modification of
      their surfaces by adsorbed chlorides are tentatively attributed to positive
      charging of the nanoparticles during the electrocatalytic overdeposition of Au
      over Ag seeds.

PMID- 15875876
TI  - Structure of hybrid colloid-polymer xerogels.
AB  - Crack-free monolithic gels were prepared from different mixtures of colloidal
      silica with a sol solution containing tetraethoxysilane, under powerful
      ultrasonic agitation (sonosol). Recently, information on the structure of these
      gels, inferred from N2 adsorption and mercury intrusion porosimetry, was
      presented. In the present paper, these data were used to construct structural
      models of the gels using Monte Carlo calculations on the basis of random close
      packing (RPC) premises. In addition, the structure of gels under study was
      investigated by transmission and scanning electron microscopy. The material can
      be described as a composite in which the sonogel is the matrix and the colloid
      particles the reinforcing phase. For low colloid content, the colloid forms
      discrete clusters, and the main structural characteristic of sonogels, i.e., a
      network of uniformly sized particles of approximately 3-4-nm radius, remains
      unmodified. However, for high colloid silica content, a multimode distribution
      appears, the structure is discontinuous, and only colloid aggregates larger than
      100 nm are observed. For medium colloid content, aggregates of approximately 50
      100 nm can be seen, but the sonogel structure extends throughout the whole
      material. By the processing method and election of a suitable precursor
      concentration, it is possible to design the composite for specific purposes.

PMID- 15875877
TI  - Synthesis of poly(methyl methacrylate) nanocomposites via emulsion polymerization
      using a zwitterionic surfactant.
AB  - The synthesis of nanocomposites via emulsion polymerization was investigated
      using methyl methacrylate (MMA) monomer, 10 wt % montmorillonite (MMT) clay, and
      a zwitterionic surfactant octadecyl dimethyl betaine (C18DMB). The particle size
      of the diluted polymer emulsion was about 550 nm, as determined by light
      scattering, while the sample without clay had a diameter of about 350 nm. The
      increase in the droplet size suggests that clay was present in the emulsion
      droplets. X-ray diffraction indicated no peak in the nanocomposites. Transmission
      electron microscopy showed that emulsion polymerization of MMA in the presence of
      C18DMB and MMT formed partially exfoliated nanocomposites. Differential scanning
      calorimetry showed an increase of 18 degrees C in the glass transition
      temperature (Tg) of the nanocomposites. A dynamic mechanical thermal analyzer
      also verified a similar Tg increase, 16 degrees C, for the partially exfoliated
      nanocomposites over poly(methyl methacrylate) (PMMA). Thermogravimetric analysis
      indicated a 37 degrees C increase in the decomposition temperature for a 20 wt %
      loss. A PMMA nanocomposite with 10 wt % C18DMB-MMT was also synthesized via in
      situ polymerization. This nanocomposite was intercalated and had a Tg 10 degrees
      lower than the emulsion nanocomposite. The storage modulus of the partially
      exfoliated emulsion nanocomposite was superior to the intercalated structure at
      higher temperatures and to the pure polymer. The rubbery plateau modulus was over
      30 times higher for the emulsion product versus pure PMMA. The emulsion technique
      produced nanocomposites of the highest molecular weight with a bimodal
      distribution. This reinstates that exfoliated structures have enhanced thermal
      and mechanical properties over intercalated hybrids.

PMID- 15875878
TI  - Microwave synthesis of core-shell gold/palladium bimetallic nanoparticles.
AB  - The microwave-assisted polyol reduction method was applied to the synthesis of
      core-shell gold/palladium bimetallic nanoparticles by the simultaneous reduction
      of the AuIII and PdII ions. The thickness of the palladium shell was calculated
      to be approximately 3 nm, and the gold core diameter is 9 nm. The structure and
      composition of the bimetallic particles were characterized by high-resolution
      transmission electron microscopy equipped with a nanoarea energy-dispersive X-ray
      spectroscopy attachment, transmission electron microscopy, X-ray diffraction, and
      X-ray photoelectron spectroscopy.

PMID- 15875879
TI  - Thermodynamic stability of clusters of molybdenum oxide.
AB  - We show that a single geometrical rule underlies the stability of
      "polyoxomolybdates", the variety of clusters of molybdenum(VI) oxide in
      (acidified) aqueous solution that are found experimentally. We predict that upon
      increasing the proton or total molybdenum oxide concentration, the average size
      of the clusters increases. We compare our predictions with results from
      ultracentrifugation experiments and with data in the literature. Finally, it is
      shown that the formation of metal oxide clusters is thermodynamically equivalent
      to the formation of surfactant micelles.

PMID- 15875880
TI  - Large-scale fabrication of tower-like, flower-like, and tube-like ZnO arrays by a
      simple chemical solution route.
AB  - Large-scale arrayed ZnO crystals with a series of novel morphologies, including
      tower-like, flower-like, and tube-like samples, have been successfully fabricated
      by a simple aqueous solution route. The morphology and orientation of the
      obtained ZnO crystal arrays can be conveniently tailored by changing the
      reactants and experimental conditions. For example, the tower-like ZnO crystal
      arrays were obtained in a reaction solution system including zinc salt, ammonia,
      ammonium salt, and thiourea, and the orientation of these tower-like crystals
      could be controlled by the contents of these reactants. Flower-like ZnO arrays
      were obtained at lower temperatures, and tube-like ZnO arrays were obtained by
      ultrasonic pretreatment of the reaction system. The growth mechanism of the tower
      like and tube-like ZnO crystals was investigated by FESEM. The results show that
      tower-like crystals grow layer by layer, while tube-like crystals grow from
      active nanowires. Ultrasonic pretreatment is proved to be effective in promoting
      the formation of active nuclei, which have important effects on the formation of
      the tube-like ZnO crystals. In addition, large-scale arrays of these ZnO crystals
      can be successfully synthesized onto various substrates such as amorphous glass,
      crystalline quartz, and PET. This implies this chemical method has a wide
      application in the fabrication of nano-/microscale devices.

PMID- 15875881
TI  - Modification of the surface properties of porous nanometric zirconia particles by
      covalent grafting.
AB  - We here report on the covalent grafting of various phosphated species (phosphoric
      acid, phenylphosphonic acid, and octyl phosphate) onto the surface of monoclinic
      zirconia nanoparticles obtained by hydrothermal treatment of zirconium acetate.
      The initial particles are 60 nm aggregates of nanometric primary grains and
      present an inner porosity. Small-angle X-ray scattering shows that the high
      specific area of the colloidal particles (450 m2 x g(-1)) decreases to 150 m2 x
      g(-1) upon drying. Therefore, phosphated reactants can access the whole internal
      surface of the aggregates only before drying. The surface of the particles can be
      covered with functional groups bound through a variable number of Zr-O-P bonds.
      Several factors probably enhance the reaction between the particles and the
      phosphates or phosphonates: the large specific area of the particles, a fully
      accessible porous network, and a large concentration of surface terminal groups.
      At the same time, the morphology of the particles is well preserved upon
      grafting. This is due to the good crystallinity of the primary grains that
      constitute the particles. In addition, the grafting drastically modifies the
      surface properties of the colloids. For example, the polarizability of the
      particles decreases in the sequence -POH > as-prepared ZrO2 > -PC6H5 > -POC8H17.
      Furthermore, the grafting of octyl phosphate allows exclusion of water from pores
      of 2 nm radius, up to hydrostatic pressures of 20 MPa.

PMID- 15875882
TI  - Polymer patterns in evaporating droplets on dissolving substrates.
AB  - Self-organized polymer patterns resulting from the evaporation of an organic
      solvent drop on a soluble layer of polymer are investigated. The patterns can be
      modulated by changing the rate of evaporation and also the rate of substrate
      dissolution controlled by its solubility. Both of these affect the contact zone
      motion and its instabilities, leading to spatially variable rates of substrate
      etching and redeposition that result from a complex interplay of several factors
      such as Rayleigh-Benard cells, thermocapillary flow, solutal Marangoni flow, flow
      due to differential evaporation, osmotic-pressure-induced flow, and contact-line
      pinning-depinning events. The most complex novel pattern, observed at relatively
      low rates of evaporation, medium solubility, and without macroscopic contact-line
      stick-slip, consists of a regularly undulating ring made up of a bundle of
      parallel spaghetti-like threads or striations and radially oriented fingerlike
      ridges. Increased rate of evaporation obliterates the polymer threads, producing
      more densely packed fingers and widely separated multiple rings due to a frequent
      macroscopic pinning-depinning of the contact line. Near-equilibrium conditions
      such as slow evaporation or increased solubility of the substrate engender a
      wider and less undulating single ring.

PMID- 15875883
TI  - Synthesis and crystallization of hybrid spherical colloids composed of
      polystyrene cores and silica shells.
AB  - The Stober method has been adopted to prepare hybrid core-shell particles by
      coating the surfaces of monodisperse polystyrene beads with uniform silica
      shells. Polystyrene beads with diameters in the range of 0.1-1.0 microm have been
      successfully demonstrated for use with this process, and the thickness of the
      silica coating could be controlled in the range of 50-150 nm by adjusting the
      concentration of tetraethoxysilane, the deposition time, or both. The morphology
      and surface smoothness of the deposited silica were found to strongly depend on a
      number of parameters such as the surface functional groups on the polymer beads,
      the pH value of the medium, and the deposition time. Hollow spheres made of
      silica could be obtained by selectively removing the polymer cores via
      calcination in air at an elevated temperature or by wet etching with toluene.
      These core-shell colloids were also explored as building blocks to fabricate long
      range ordered lattices (or colloidal crystals) that exhibited stop bands
      different from those assembled from spherical colloids purely made of either
      polystyrene or silica.

PMID- 15875884
TI  - Electroless deposition of poly(2-alkoxyaniline)s.
AB  - The in situ deposition of poly(2-alkoxyaniline)s onto oxide surfaces is reported.
      It is demonstrated that the identity of the substrate can have a pronounced
      effect on the polymerization rate of these substituted polyanilines. Poly(2
      alkoxyaniline)s deposit efficiently onto indium-doped tin oxide (ITO), but
      deposition onto quartz proceeds slowly. The critical stage in the deposition
      process is shown to be polymerization of the adsorbed oligomeric species. When
      this polymerization process is catalyzed by the surface, polymer growth is
      enhanced, and we find that conducting substrates mediate this apparent catalytic
      process. We demonstrate selective deposition by growing poly(2-alkoxyaniline)
      adlayers onto patterned ITO/quartz substrates.

PMID- 15875885
TI  - Molecular dynamics study of the effect of atomic roughness on the slip length at
      the fluid-solid boundary during shear flow.
AB  - A systematic study into the effect of solid roughness on the slip boundary
      condition during shear flow is presented. Atomic roughness is modeled by varying
      the size and spacing between solid atoms at constant packing fraction while the
      interaction parameters and the thermodynamic state of the fluid are kept
      constant. It is shown that the fluid structure as manifest in the amplitude of
      the density oscillations increases with increasing smoothness of the surfaces.
      The fluid-solid slip length is shown to exhibit nonmonotonic behavior as the
      solid structure is varied from smooth to rough. Slip occurs for both smooth and
      rough surfaces, and stick occurs only for surfaces commensurate with the fluid.

PMID- 15875886
TI  - Through-mask anodic patterning of copper surfaces and film stability in
      biological media.

PMID- 15875887
TI  - Breast cancer risk in Hispanic agricultural workers in California.
AB  - In a registry-based case-control study of breast cancer in farm labor union
      members in California, 128 breast cancer (BC) cases newly diagnosed in 1988--2001
      and 640 cancer-free controls were investigated. Stage and grade of disease at
      diagnosis were about the same as in the California Hispanic population. Risk of
      breast cancer was not associated with work with any specific crops or commodities
      except mushrooms, where the adjusted odds ratio (OR) was 6.00 (95% CI 2.01-18.0).
      Controlling for covariates, adjusted ORs (and 95% CIs) for breast cancer in
      quartiles of pesticide use were 1.00, 1.30 (0.73-2.30), 1.23 (0.67-2.27), and
      1.41 (0.66-3.02). Chlordane, malathion, and 2,4-D were associated with increased
      risk. Risk associated with chemical use was stronger in younger women, those with
      early-onset breast cancer, and those diagnosed earlier (1988--1994).

PMID- 15875888
TI  - Mercury levels in urine and hair of children in an Andean gold-mining settlement.
AB  - This field study investigated mercury (Hg) levels in urine and hair of Andean
      children of indigenous Saraguro and Metizo gold miners in the Nambija, Ecuador
      gold mining settlement. Spot samples of urine and hair samples were collected
      concurrently from 80 children each. Urine samples were used to determine the
      inorganic Hg burden, while hair samples were used as an index of methylmercury
      (MeHg) exposure from consumption of Hg contaminated fish. The mean level of Hg in
      urine (HgU) was 10.9 microg/L, and the mean level in hair (HgH) was 6.0 microg/g.
      Regression analysis showed a significant association (r = 0.404, p = 0.0007)
      between matched HgU and HgH samples. Mean HgU and HgU levels tended to be higher
      for children aged 6-14 years than for a younger group. The wide range of Hg
      levels in the urine and hair of Andean children of gold miners may place them at
      risk for neurodevelopmental and learning disorders.

PMID- 15875889
TI  - A pilot study of blood lead levels and neurobehavioral function in children
      living in Chennai, India.
AB  - The relationship between blood lead level and neurodevelopment was assessed in a
      pilot cross-sectional study of 74 4-14-year-old children in Chennai, India. Mean
      blood lead level was 11.1 microg/dL (2.5-38.3). The Binet-Kamath IQ test and the
      Wide Range Assessment of Visual Motor Activity (WRAVMA) were administered to 58
      children. Teachers completed the Connor's Behavioral Rating Scale. Excluding two
      outliers, IQ and WRAVMA composite scores were inversely related to blood lead
      level, with an effect size of approximately 6 points decline for a 10-microg/dL
      increase in blood lead. Children in the highest and lowest blood lead quartiles
      had mean IQs of 95.6+/-13.3 and 102.0+/-22.5, respectively. Behavior ratings were
      not associated with blood lead level. Lead exposure is a significant problem
      among Indian children, with many having blood lead levels associated with
      increased neurodevelopmental risk.

PMID- 15875890
TI  - Adverse impact of insecticides on the health of Palestinian farm workers in the
      Gaza Strip: a hematologic biomarker study.
AB  - To evaluate the health impact of insecticides on Palestinian farm workers in the
      Gaza Strip, the study assessed biomarkers in farm workers who used
      organophosphorus insecticides. Serum cholinesterase and complete blood count were
      determined before and after spraying of organophosphorus insecticides. Burning
      sensations in eyes/face (62.5%), itching/skin irritation (37.5%), and chest
      symptoms (29.2%) were reported. Serum butyrylcholinesterase (SBuChE) was
      significantly decreased at the end of the work day. Burning sensations in
      eyes/face and skin rash were significantly associated with inhibition of SBuChE
      activity (p < 0.05). Younger workers were more affected. Leukocyte and platelet
      counts were increased and hemoglobin decreased significantly, reflecting acute
      poisoning. Monitoring of SBuChE and hematologic parameters of farm workers could
      be useful to predict and prevent health hazards of pesticides.

PMID- 15875891
TI  - Indoor air pollution from biomass fuels and respiratory health of the exposed
      population in Nepalese households.
AB  - A cross-sectional assessment of indoor air quality in Nepal and its health
      effects revealed that solid biomass fuels (animal dung, crop residue, and wood)
      were the main sources of indoor air pollution affecting health. The average smoke
      level (PM10) in kitchens using biomass fuels was about three times higher than
      that in those using cleaner fuels (kerosene, LPG, and biogas). Respondents in 98
      randomly selected households included 168 who cooked daily meals, of whom 94%
      were disadvantaged women. Biomass smoke caused significantly more respiratory
      disorders than did cleaner fuels. Categorized data analysis demonstrated
      significant associations between biomass smoke pollution and respiratory symptoms
      such as cough; phlegm; breathlessness; wheezing; and chronic respiratory diseases
      such as COPD and asthma. The prevalences of respiratory illnesses and symptoms
      were considerably higher in those living in mud and brick houses compared with
      concrete houses. Prevalences were also higher in those living on hills and in
      rural areas compared with flatland and urban areas.

PMID- 15875892
TI  - Lead exposure and semen quality among traffic police in Arequipa, Peru.
AB  - This study examined lead exposure (n = 43) and semen quality (n = 18) among
      traffic police officers in Arequipa, Peru, where leaded gasoline is used. Blood
      lead (PbB) was measured using atomic absorption spectrophotometry, and semen was
      analyzed following World Health Organization (WHO) protocol. Mean PbB was 48.5
      microg/dL. Although current PbB was associated with declines in several semen
      parameters (sperm morphology, concentration and total number of sperm), only
      sperm motility and viability differed significantly between the < or = 40
      microg/dL and > 40 microg/dL categories, and decreased with increasing PbB in
      simple linear regression. Traffic police are an indicator group for excessive
      ambient lead exposure, and these results support earlier findings on the male
      reproductive toxicity of lead. The results should be interpreted cautiously since
      the numbers were small and the analysis was unable to control for all potential
      confounders due to incomplete data.

PMID- 15875893
TI  - Occupational light-vehicle use and OHS legislative frameworks: an Australian
      example.
AB  - Occupational light vehicle (OLV) use and associated exposures and hazards in the
      Australian context are described. Available insurance data indicate that the OLV
      injury burden, which is greater than that of other work-road users, is growing as
      OLV use changes incidental to workers' primary occupations and work patterns.
      Legislation that affects OLV users is reviewed and the shifting of the burden of
      responsibility for injured or killed OLV users between workers' compensation,
      motor accident insurance and public health systems is described. Changes to OHS
      regulatory frameworks are proposed to better address OLV-relevant policy and
      practice. These issues are relevant for many international jurisdictions.

PMID- 15875894
TI  - Hospital-based survey of pesticide poisoning in Japan, 1998--2002.
AB  - Data concerning clinical cases of pesticide poisoning from 1998 to 2002 from the
      hospitals affiliated with the Japanese Association of Rural Medicine were
      analyzed. 346 cases of poisoning by agricultural chemicals were reported from 65
      hospitals. Suicides accounted for 70% of pesticide poisoning cases, followed by
      accidental exposures during spraying work (16%) and accidental ingestion (8%).
      The majority of cases were acute or subacute systemic poisonings (90%), followed
      by acute dermatitis (5%) and chemical burns (3%). Organophosphate insecticide was
      the most frequent inducer of clinical cases (36%), followed by bipyridylium
      herbicide (20%) and carbamate insecticide (6%). The death rate from poisoning by
      the herbicide paraquat was more than 70% of clinical cases, even though it is a
      low-concentration product, whereas those from the alternative herbicides,
      glufosinate and glyphosate, were less than 10%.

PMID- 15875895
TI  - A global survey of occupational health competencies and curriculum.
AB  - The World Health Organization has identified a worldwide shortage of occupational
      health professionals, but evidence suggests that the work and education of these
      professionals vary across countries. This survey examined the professional
      development of occupational physicians, occupational nurses, industrial
      hygienists, and ergonomists in terms of practice competencies and academic
      curriculum. Of 89 countries that received the survey, 48 (54%) responded.
      Important differences in competencies and curricula were identified for all
      groups. More competencies were identified more frequently in developed countries.
      Academic programs existed more often in developed countries, but curriculum
      contents varied. The study provides a concrete reference point for discussion and
      development of competencies and curriculum.

PMID- 15875896
TI  - Unrecognized or potential risk factors for childhood cancer.
AB  - Epidemiologic methods only seldom identify causes of childhood cancer associated
      with relative risks below a factor of 1 1/2-2. Children are at risk of exposure
      to over 15,000 high-production-volume chemicals and are certainly exposed to many
      carcinogens. The individual impacts of most of these agents are too small to be
      detected, but collectively these unrecognized factors are potentially important.
      Infants and children are exposed to higher levels of some environmental toxicants
      and may also be more sensitive. During intrauterine development and childhood,
      cells divide frequently, and the mutant frequency rises rapidly. Endocrine
      related cancers or susceptibility to cancer may result from developmental
      exposures rather than from exposures existing at or near the time of diagnosis.
      That environmental exposures may be important causes of childhood cancers is
      indicated by associations of enzyme polymorphisms with risk.

PMID- 15875897
TI  - Suppression bias at the Journal of Occupational and Environmental Medicine.
AB  - When the Journal of Occupational and Environmental Medicine rejected an article
      on corporate suppression of science on the grounds that the topic "was not a high
      priority" for journal readers, the author bought advertising space in JOEM to
      present his findings. The JOEM editor regretted he had not seen the ad to prevent
      its publication, and subsequently allowed the corporate-sponsored authors of a
      criticized study to respond to the advertisement. The editor then refused to
      allow the ad's author to respond in turn, suppressing scientific information with
      the apparent intent of protecting the interests and profits of the corporate
      sponsor. A reputable journal has a responsibility to eschew corporate interests
      and work to uncover science hidden by interests that do not prioritize the
      pursuit of truth. JOEM needs to re-examine its priorities.

PMID- 15875898
TI  - Conflicts of interest and scientific integrity.
AB  - The encroachment of conflicts of interest on the peer-review process of
      scientific journals is discussed, with particular reference to a current example.
      The authors stress the need for transparency of the connections among authors,
      reviewers, publishers, editors, and sources of funding to prevent erosion of
      trust in the scientific integrity of such publications.

PMID- 15875899
TI  - Protecting workers' health and safety in the globalizing economy through
      international trade treaties.
AB  - An illustrated account describes the shortcomings of international trade
      agreements, particularly NAFTA, with respect to worker protection in Mexico, and
      outlines measures needed to correct them.

PMID- 15875900
TI  - World Trade Organization, ILO conventions, and workers' compensation.
AB  - The World Trade Organization, the World Bank, and the International Monetary Fund
      can assist in the implementation of ILO Conventions relating to occupational
      safety and health in developing countries. Most countries that seek to trade
      globally receive permission to do so from the WTO. If the WTO required member
      countries to accept the core ILO Conventions relating to occupational safety and
      health and workers' compensation, it could accomplish something that has eluded
      international organizations for decades. International workers' compensation
      standards are seldom discussed, but may at this time be feasible. Acceptance of a
      minimum workers' compensation insurance system could be a requirement imposed on
      applicant nations by WTO member states.

PMID- 15875901
TI  - The James Hardie story: asbestos victims' claims evaded by manufacturer.
AB  - The Australian government is pursuing legal avenues to bring to financial
      accountability giant asbestos manufacturer James Hardie Ltd., which has been
      responsible for vast numbers of asbestos-related deaths and illnesses in
      Australia and other countries, and has been attempting by unethical and possibly
      criminal ploys to avoid compensating victims.

PMID- 15875902
TI  - Scientific evidence fails to support fluoridation of public water supplies.

PMID- 15875904
TI  - Overlap between neurodegenerative disorders.
AB  - Neurodegenerative disorders are characterized by the formation of distinct
      pathological changes in the brain, including extracellular protein deposits,
      cellular inclusions, and changes in cell morphology. Since the earliest published
      descriptions of these disorders, diagnosis has been based on clinicopathological
      features, namely, the coexistence of a specific clinical profile together with
      the presence or absence of particular types of lesion. In addition, the molecular
      profile of lesions has become an increasingly important feature both in the
      diagnosis of existing disorders and in the description of new disease entities.
      Recent studies, however, have reported considerable overlap between the
      clinicopathological features of many disorders leading to difficulties in the
      diagnosis of individual cases and to calls for a new classification of
      neurodegenerative disease. This article discusses: (i) the nature and degree of
      the overlap between different neurodegenerative disorders and includes a
      discussion of Alzheimer's disease, dementia with Lewy bodies, the fronto-temporal
      dementias, and prion disease; (ii) the factors that contribute to disease
      overlap, including historical factors, the presence of disease heterogeneity, age
      related changes, the problem of apolipoprotein genotype, and the co-occurrence of
      common diseases; and (iii) whether the current nosological status of disorders
      should be reconsidered.

PMID- 15875903
TI  - Texaco and its consultants.

PMID- 15875905
TI  - Degeneration of the inferior olive in spinocerebellar ataxia 6 may depend on
      disease duration: report of two autopsy cases and statistical analysis of autopsy
      cases reported to date.
AB  - This report concerns a clinicopathological study of two autopsied patients with
      spinocerebellar ataxia 6 (SCA6), and a statistical analysis between neuronal loss
      of the inferior olive and disease duration of 15 SCA6 autopsy cases reported to
      date, including the two cases reported in this study. Cases 1 and 2 came from
      independent Japanese families. Case 1 developed gait disturbance at age 35 years
      and died at age 78 years; she had a CAG-repeat expansion of the SCA6 gene
      (25/13). Case 2 presented with gait disturbance at age 68 years and died at age
      78 years; he had an expanded CAG-repeat of the SCA6 gene (22/13).
      Neuropathological examination of both cases disclosed not only neuronal loss of
      the Purkinje cells and inferior olive, but also some unnoticed features,
      including cactus-like expansion of the dendrite of Purkinje cells and relative
      preservation of Golgi cells in the granular layer of the cerebellum. Exploratory
      statistical analysis between 11 SCA6 autopsy cases with neuronal loss in the
      inferior olive (average disease duration: 27 years) and four SCA6 autopsy cases
      without neuronal loss in the olive (average disease duration: 14.5 years) was
      investigated by Kaplan-Meier estimates of survival and log-rank test,
      retrospectively. Kaplan-Meier estimates of survival revealed an obvious
      difference between the two groups. Survival of 10 years after the disease onset
      was 90.9% in the former 11 SCA6 autopsy cases, but was 50% in the latter four
      SCA6 autopsy cases. Furthermore, a log-rank test on the two groups disclosed a
      significant difference (P=0.0450). We postulate that the neuronal loss of the
      inferior olive in SCA6 may depend on disease duration.

PMID- 15875906
TI  - Establishment and partial characterization of five malignant glioma cell lines.
AB  - Five malignant glioma cell lines (YMG1, 2, 3, 4, and 5) were established from
      surgical specimens obtained from patients with glioblastoma or anaplastic
      astrocytoma, and these lines were partially characterized. Three glioma cell
      lines (YMG1, 3, and 5) were weakly positive for GFAP by Western blot analysis and
      two cell lines were negative. S-100 protein was positive in all glioma cell
      lines. The expression of p53, p16, p15, cyclin-dependent kinase 4 (CDK4), and EGF
      receptor (EGFR) proteins was examined by Western blotting. YMG1 and 2 cell lines
      showed accumulation of p53 protein and loss of p16 and p15 expression. YMG3 and 4
      showed accumulation of p53 protein and expression of p16 and p15 proteins. YMG5
      revealed weak expression of p53 protein, suggesting wild-type p53, and loss of
      p16 and p15 expression. All cell lines expressed various levels of CDK4 protein.
      YMG1, 2, and 3 showed higher EGFR protein expression and YMG4 and 5 showed lower
      EGFR expression compared to U251 glioblastoma cells, which express high levels of
      EGFR. Fluorescence in situ hybridization analysis for EGFR gene expression did
      not show any amplification in the glioma cell lines. Immunohistochemical studies
      revealed that the patterns of p53 and EGFR expressions in the original tumor
      tissues were mostly correlated with those in the malignant glioma cell lines.
      These results suggest that the characteristics of p53 and EGFR expression in the
      malignant glioma cell lines were passed over from the original tumor tissues.
      These newly established malignant glioma cell lines can be used for further
      analysis of the mechanisms of tumor growth and progression.

PMID- 15875907
TI  - Sporadic fatal insomnia with spongiform degeneration in the thalamus and
      widespread PrPSc deposits in the brain.
AB  - We report a case of human prion disease of 29 months duration in a 74-year-old
      Japanese man. The disease started with progressive sleeplessness and dementia.
      MRI showed gradually progressive cerebral atrophy. Neuronal loss, spongiform
      change and gliosis were evident in the thalamus and cerebral cortex, as well as
      in the striatum and amygdaloid nucleus. In the cerebellar cortex, mild-to
      moderate depletion of Pukinje cells and spongiform change were observed. Mild
      neuronal loss in the inferior olivary nucleus was also seen. Immunohistochemistry
      revealed widespread perivacuolar deposits of abnormal prion protein (PrPsc) in
      the cerebral cortex, thalamus, basal ganglia, and brainstem, and minimal plaque
      like deposits of PrPSc in the cerebellar cortex. In the cerebellar plaque-like
      deposits, the presence of amyloid fibrils was confirmed ultrastructurally. The
      entire pathology appeared to lie halfway between those of CJD and fatal insomnia,
      and further demonstrated the relationship between spongiform degeneration and
      PrPSc deposits, especially in the diseased thalamus. By immunoblotting, the
      thalamus was shown to contain the lowest amount of PrPSc among the brain regions
      examined. The PrPSc of type 2, in which the ratio of the three glycoforms was
      compatible with that of sporadic fatal insomnia (MM2-thalamic variant) reported
      previously, was also demonstrated. Analysis of the prion protein gene (PRNP)
      showed no mutation, and homozygosity for methionine at codon 129. In conclusion,
      we considered that this patient had been suffering from sporadic, pathologically
      atypical fatal insomnia.

PMID- 15875908
TI  - Desmoplastic non-infantile ganglioglioma.
AB  - Desmoplastic ganglioglioma is a rare, markedly desmoplastic variant of
      ganglioglioma that usually presents in the first year of life. It is a mixed
      glial and neuronal cerebral tumor. A few cases of desmoplastic ganglioglioma have
      been reported in non-infantile patients. We report a case of desmoplastic
      ganglioglioma in a 14-year-old boy. The patient presented with a large solid
      cystic mass with mild peritumoral edema in the right posterior parieto-occipital
      region with direct contact to the falx cerebri. Histopathological examination
      revealed a low-grade glial tumor with prominent desmoplasia including
      hypocellular collagenous areas. The tumor was well demarcated with respect to the
      surrounding brain. Ganglion cells with dysplastic features were present in the
      tumor and clustered in some areas. Focal lymphocytic infiltration was also
      observed. Mitotic activity was very low. Immunohistochemistry revealed glial
      fibrillary acidic protein positivity in the astrocytic cells hidden in the
      desmoplastic tissue. Synaptophysin and neuron specific enolase were positive in
      ganglion-like neuronal cells. The MIB-1 labeling index was less than 1%. This
      present case confirms that desmoplastic ganglioglioma can be present in young
      adult patients with its characteristic radiologic features.

PMID- 15875909
TI  - Miliary brain metastases presenting as rapidly progressive dementia.
AB  - We report the case of a 79-year-old woman who developed a rapidly progressive
      dementia (RPD) with severe memory impairment, early visual hallucinations and
      extrapyramidal signs. Symptoms started suddenly after hip replacement surgery
      following an accidental fall. Motor epileptic seizures appeared at the end of the
      illness. Dementia worsened gradually leading to akinetic mutism. She died five
      and a half months after the onset of symptoms. MRI showed cerebral atrophy but
      failed to detect any other lesion. Results of all laboratory tests performed were
      negative. After the most frequent treatable diseases were excluded, the diagnosis
      of dementia with Lewy bodies was initially considered. CJD was also suggested
      based on the rapid evolution of the disease and the positivity of 14-3-3 protein
      in CSF. Neuropathological examination revealed an extensive miliary metastatic
      dissemination from an unknown primary adenocarcinoma. Pulmonary origin was
      suggested according to the immunohistochemical profile. Histopathological changes
      of Alzheimer's disease were also observed in the cerebral cortex and hippocampus.
      Neither Lewy bodies nor PrP deposits were found. The sudden onset of the dementia
      just after the hip replacement surgery raises the possibility of a pathological
      fracture with secondary tumoral microembolic dissemination. Despite its rarity,
      this entity should be included in the differential diagnosis of RPD. This case
      illustrates the definite importance of neuropathological post-mortem examination
      in order to elucidate the different types of dementia.

PMID- 15875910
TI  - Temporal bone chondroblastoma: a review.
AB  - The objective of this paper was to review temporal bone chondroblastomas in
      regard to their presentation, radiographic findings, histopathology, and
      treatment. A case report of a 38-year-old man who presented with the left-sided
      hearing impairment and temporal swelling was reviewed. A CT scan revealed an
      osteolytic lobulated expansile mass. MRI depicted two cystic components with
      fluid-fluid level and enhanced solid mass. Immunohistochemical study of S-100 was
      performed using avidinbiotin-complex method. The tumor was totally removed, with
      eroded squamous bone and temporal muscle, via the left zygomatic-extended middle
      fossa approach. The pathology of the tumor showed that the tumor cell was spindle
      shaped, along with multinucleated giant cells. These cells had oval to polygonal
      nuclei; some cells showed grooved nuclei. Intercelluar calcification and
      hemorrhagic components were also observed in the tumor. Tumor cells were strongly
      positive for S-100 protein. Temporal bone chondroblastomas are extremely rare
      osseous tumors with only 45 cases previously reported in the published
      literature. They may be confused with more common lesions seen in the temporal
      bone. Diagnostic radiology, including CT and/or MRI, as well as
      immunohistochemical staining with S-100 protein, may assist in making the
      diagnosis. Treatment is complete surgical excision with preservation of vital
      neurovascular structures.

PMID- 15875911
TI  - Argyrophilic grain disease presenting with frontotemporal dementia: a
      neuropsychological and pathological study of an autopsied case with presenile
      onset.
AB  - A right-handed Japanese man with no consanguinity exhibited personality changes,
      speech disorder and abnormal behaviors, such as stereotypical, running-away,
      environment-dependent, and going-my-way behaviors, since the age of 49 years. At
      age 52 years, neuropsychological examination revealed frontal lobe dysfunctions,
      mild memory impairment, and transcortical sensory aphasia. MRI showed symmetrical
      severe atrophy of the anterior part of the temporal and frontal lobes. The
      clinical diagnosis was FTD. He died at age 54 years after a clinical illness of
      approximately 5 years. Numerous argyrophilic grains were observed throughout the
      limbic system, temporal lobe, frontal lobe and brainstem. In addition, there were
      many tau-positive neurons and glial cells. These findings are all compatible with
      argyrophilic grain disease (AGD). Our case, however, is atypical AGD because of
      the young age of onset of the disease and sharply circumscribed cortical atrophy
      exhibiting severe neuronal loss and gliosis. Our case, together with some other
      similar cases of atypical AGD, gives rise to the possibility that this type of
      AGD would constitute a part of pathological background of FTD.

PMID- 15875912
TI  - A 30-year-old male treated by neurosurgery against temporal lobe epilepsy.

PMID- 15875913
TI  - Corpora amylacea in a mature cystic teratoma of the ovary.

PMID- 15875914
TI  - HIV/AIDS: the epidemic, its impact and turning the tide.

PMID- 15875915
TI  - Pooling tides: the convergence of migration, congregation, and tuberculosis.

PMID- 15875916
TI  - Personal respiratory protection and prevention of occupational tuberculosis.

PMID- 15875917
TI  - Tuberculosis in children with human immunodeficiency virus infection.
AB  - For a number of reasons--but especially the human immunodeficiency virus (HIV)
      epidemic--tuberculosis (TB) is currently increasing in many parts of the world
      where it threatens the lives of millions of infants and children. The diagnosis
      of childhood TB, which has always been difficult, is now even more challenging in
      infants and children co-infected with HIV and Mycobacterium tuberculosis. Both TB
      and HIV infection require multiple drugs for effective treatment and to prevent
      the development of resistance by the infecting agents. Drug-drug interactions are
      therefore common, and knowledge of these is essential in the management of dually
      infected infants and children. Due to problems with drug toxicity and the need
      for prolonged treatment, compliance is also a major issue in these children.
      Chemoprophylaxis against TB in HIV-infected children needs further research, as
      do the pharmacokinetics of antiretroviral drugs in children. Integrated
      management of children co-infected with TB and HIV should be encouraged,
      especially in resource-poor settings.

PMID- 15875918
TI  - Manifestations and outcome of extra-pulmonary tuberculosis: impact of human
      immunodeficiency virus co-infection.
AB  - SETTING: Metropolitan New Orleans. OBJECTIVE: To determine the impact of human
      immunodeficiency virus (HIV) co-infection on the manifestations and outcome of
      extra-pulmonary tuberculosis (EPTB). DESIGN: Retrospective analysis of 136
      patients diagnosed with EPTB between 1 January 1993 to 31 December 2001.
      Characteristics of EPTB were compared by HIV serostatus. RESULTS: Of those tested
      for HIV (n = 87), 42.5% were seropositive. Except for a higher frequency of
      disseminated TB among co-infected persons, the manifestations, laboratory
      diagnostic yield and outcome of EPTB were similar between HIV-infected and non
      infected persons. The overall fatality rate was 20%; HIV-infected patients had a
      three-fold higher mortality compared to non-infected persons. In multivariate
      logistic regression analysis, factors associated with death were: HIV
      seropositive (adjusted odds ratio [aOR] 5.2, 95% CI 1.1-24.65) compared to HIV
      seronegative, disseminated and meningeal compared to lymphatic disease (aOR
      16.87, 95% CI 12.31-123.34), and lack of TB treatment compared to receipt of TB
      treatment (aOR 29.23, 95% CI 14.47-191.23). CONCLUSION: Manifestations of EPTB
      were non-specific and did not differ between HIV-infected and non-infected
      persons. Severe disease, lack of TB treatment and HIV co-infection were
      associated withdeath. Approaches are needed to reduce EPTB morbidity and
      mortality, especially among HIV-infected persons.

PMID- 15875919
TI  - Patterns of anti-tuberculosis drug resistance among HIV-infected patients in
      Maputo, Mozambique, 2002-2003.
AB  - SETTING: Two tuberculosis (TB) reference hospitals in Maputo, Mozambique.
      OBJECTIVES: To assess the pattern of TB drug resistance and its risk factors in
      human immunodeficiency virus (HIV) patients. DESIGN: Adult HIV-positive patients
      with TB diagnosed by culture of sputum or bronchial washing were enrolled during
      2002-2003. Cultures of 111 patients were tested for rifampicin, isoniazid,
      streptomycin and ethambutol sensitivity. Chest X-ray, haemoglobin (Hb), total
      lymphocyte and CD4 counts were also performed. RESULTS: Overall resistance to any
      drugs was found in 18% and multidrug-resistant TB (MDR-TB) in 9%. New cases of TB
      accounted for 62% of the studied group. Drug resistance in this subgroup was 13%
      compared with 26.3% in the previously treated subgroup, and MDR-TB was 5.8% vs.
      15.8%. All patients presented Hb levels < 9 g/dl and total lymphocyte counts <
      1200/microl. CD4 counts were significantly low in the drug resistance subgroup,
      with levels mostly < 100/microl. Cavities on X-ray were seen only in drug
      sensitive patients. No risk factors for drug resistance were detected.
      CONCLUSIONS: Overall observed drug resistance was 18%, and MDR-TB 9%. Previously
      treated patients had high drug resistance (26.3%) and MDR-TB (15.8%).

PMID- 15875920
TI  - Isoniazid- and rifampin-resistant tuberculosis in San Diego County, California,
      United States, 1993-2002.
AB  - SETTING: A local tuberculosis (TB) control program. OBJECTIVES: To measure trends
      in isoniazid (INH) and rifampin (RMP) resistance and identify associated factors.
      DESIGN: Retrospective review. RESULTS: Of 2883 isolates obtained from TB patients
      reported between 1993 and 2002, 287 (10%) were resistant to INH, 11 (< 1%) were
      resistant to RMP, and 40 (1%) were resistant to both (multidrug resistance
      [MDR]). There were no linear trends over time. Eighty-one per cent of patients
      with INH resistance and 85% with MDR were born outside the United States. Sixty
      three per cent of patients with drug resistance and prior TB treatment were
      treated outside the US. INH resistance was associated with race/ethnicity and
      prior treatment, RMP resistance with human immunodeficiency virus (HIV)
      infection, and MDR with non-US birth and prior treatment. Patients with INH- and
      RMP-susceptible or INH-resistant TB had higher percentages of treatment
      completion and sputum culture conversion than patients with RMP-resistant or MDR
      TB. CONCLUSIONS: INH and RMP resistance remained stable between 1993 and 2002.
      Because most patients with drug resistance were infected or initially treated
      outside the US, future reductions in drug resistance will depend not only on
      local and national efforts, but also on the success of global interventions.

PMID- 15875921
TI  - Management of multidrug-resistant tuberculosis in Italy.
AB  - SETTING: SMIRA (Italian Study on Anti-Tuberculosis Drug Resistance) network, 46
      major clinical units and 22 laboratories nationwide in Italy. OBJECTIVES: To
      determine the main features, adherence to WHO guidelines and the outcomes of
      multidrug-resistant tuberculosis (MDR-TB) patients enrolled from January 1995 to
      December 1999. DESIGN: Observational study, preceded by proficiency testing,
      according to WHO recommendations. Results were stratified by appropriate and
      inappropriate regimens (< three active drugs). Analysis of the outcomes was
      performed according to adequacy of treatment. Analysis of risk factors and
      factors predicting treatment outcomes was performed using univariate and
      multivariate analysis (level of significance P < 0.05). RESULTS: One hundred and
      twenty-seven MDR patients were diagnosed. The overall success rate was low (39%).
      Seventy per cent of cases were treated with at least three active drugs. Factors
      predicting treatment success were new MDR-TB cases (OR 3.45; 95% CI 1.22-9.78; P
      < 0.05) and treatment for > or = 12 months (OR 5.03; 95% CI 1.65-15. 31; P <
      0.05). Immigration and HIV infection were the main risk factors among new MDR-TB
      cases. CONCLUSION: The best available treatment should be provided to all newly
      diagnosed MDR-TB patients, avoiding the use of poorly modified regimens. MDR-TB
      patients should be referred to highly specialised centres.

PMID- 15875922
TI  - Results of a national study on anti-mycobacterial drug resistance in El Salvador.
AB  - SETTING: The DOTS strategy was introduced in El Salvador in 1997 and had become
      fully implemented countrywide by 2001. Previously, many deficiencies were
      identified in the management of patients with tuberculosis (TB). OBJECTIVE: To
      ascertain the prevalence of Mycobacterium tuberculosis resistant to first-line
      drugs. DESIGN: A national prospective survey was carried out in 2001 using the
      standardised World Health Organization/ International Union Against Tuberculosis
      and Lung Disease model. RESULTS: A total of 711 cultures were analysed (59% of
      total smear-positive cases); 611 were never treated and 100 were previously
      treated patients. The study showed resistance rates to isoniazid and rifampicin,
      either alone or combined (multidrug resistance, MDR), of 1.3%, 1.1% and 0.3%,
      respectively, in never treated patients, and 12%, 13% and 7%, respectively, in
      previously treated patients. CONCLUSION: The low rates of MDR-TB in El Salvador
      are puzzling, as out-patient DOTS was introduced only recently and fixed-dose
      combination tablets have not been used.

PMID- 15875923
TI  - DOTS implementation in a middle-income country: development and evaluation of a
      novel approach.
AB  - BACKGROUND: DOTS is widely accepted as the most cost-effective strategy for
      tuberculosis (TB) control. However, there is little published information
      regarding methods for implementation in middle-income countries. METHODS: Over 3
      years, the Canadian Lung Association assisted the Ecuadorian TB programme to
      implement DOTS for over half the nation's total population. A multilevel strategy
      developed by a team of Ecuadorian health professionals provided initial, in
      service, replica and reinforcement training at the local level, and training at
      national level for specialist physicians, specialist societies and medical
      schools. Evaluation was based on international guidelines for case finding,
      treatment and laboratory quality control, and costs of all implementation
      activities. RESULTS: By January 2004, DOTS training had been provided to 1954
      health professionals and 199 smear microscopy technicians, and DOTS was
      implemented in all 496 health facilities. Case detection activities at the local
      level increased substantially. Cure and treatment completion improved to 83% of
      new cases. Overall concordance of laboratory quality control readings was 98.7%.
      The total cost of DOTS implementation was US dollar 3 049 585. CONCLUSIONS: To
      achieve international targets for TB control, DOTS implementation in a middle
      income country required intensive training at the local level and at multiple
      other levels.

PMID- 15875924
TI  - Outbreak of tuberculosis in a migrants' shelter, Paris, France, 2002.
AB  - SETTING: An overcrowded 362-bed migrants' shelter in Paris, France. OBJECTIVES:
      To investigate an outbreak of tuberculosis (TB), to identify a common source of
      contamination and to prevent further transmission. METHODS: The outbreak was
      identified by radiographic screening and an active search for undeclared hospital
      treated cases, completed by strain phenotyping and a search for contact cases.
      RESULTS: Between October 2001 and October 2002, 56 cases of active TB were
      identified, 30 by radiological screening and 20 by contacting neighbouring
      hospitals. All cases involved men, with a median age of 30 years. Pulmonary
      involvement was present in 54% of cases, and nine patients were sputum smear
      positive. Thirty-four of the 37 phenotyped strains clustered together.
      CONCLUSION: The grouping of the cases in time and place, the large number of
      cases with early-stage disease and the identical RFLP banding patterns of most of
      the isolates indicate that this outbreak results from transmission that occurred
      in France. This report underlines the need for public health departments in
      industrialised countries to maintain effective anti-tuberculosis control
      programmes.

PMID- 15875925
TI  - Severe hepatotoxicity due to anti-tuberculosis drugs in Spain.
AB  - OBJECTIVES: To determine the frequency of severe hepatotoxicity due to anti
      tuberculosis (TB) drugs, and predictors of development of acute liver failure or
      of death. METHODS: A retrospective study conducted by members of the Spanish
      Society of Pneumology from 18 hospitals during 1997-2001. A case of severe
      hepatotoxicity was defined as any asymptomatic patient with a ten-fold increase
      in transaminases or three-fold increase in colostasis parameters, or, among
      patients with hepatitis symptoms, any raised hepatic parameters or development of
      hepatic failure. Predictive factors were studied using logistic regression,
      calculating odds ratios (OR) and their 95% confidence intervals (CI). RESULTS:
      One hundred and six patients developed severe hepatotoxicity. Of a total of 3510
      patients, 90 were treated for active TB (2.56%). Eleven cases (10.3%) presented
      with acute liver failure, three of whom underwent liver transplant. The global
      case fatality rate was 4.7% (five cases, three associated with alcohol use or
      hepatotoxic drugs). The predictors of poor prognosis were total bilirubin > 2
      mg/dl (OR 9.4, 95% CI 1.0-85.5) and serum creatinine > 1.5 mg/dl (OR 32.1, 95% CI
      2.4-424.6). CONCLUSIONS: Severe hepatotoxicity due to anti-tuberculosis drugs is
      associated with a high fatality rate. Prevention should be based on informing
      patients and frequent clinical and laboratory controls.

PMID- 15875926
TI  - The treatment of spinal tuberculosis: a retrospective study.
AB  - BACKGROUND: There are conflicting guidelines and variations in clinical practice
      in the management of bone tuberculosis (TB), including spinal TB. A case who
      received 6 months of treatment in line with current British Thoracic Society
      (BTS) guidelines, and subsequently relapsed, prompted a survey of treatment and
      outcomes of spinal and other bone TB. METHODS: A retrospective study examining
      the clinical features, treatment duration and outcome of patients presenting with
      spinal and other bone TB to the Leeds Teaching Hospitals National Health Service
      Trust, between 1998 and 2002. RESULTS: Forty-two patients were identified. Notes
      from 34 patients with spinal TB and four patients with TB of other bones were
      reviewed. Of eight patients who received 6 months of therapy, five relapsed. Of
      30 patients who received treatment for 9 months or longer, none relapsed (P <
      0.05). CONCLUSION: Six months of treatment, as currently recommended by the BTS,
      may be inadequate for bone TB, including spinal TB.

PMID- 15875927
TI  - Evaluation of N95 respirator use as a tuberculosis control measure in a resource
      limited setting.
AB  - SETTING: A 150-bed public Brazilian hospital that serves as reference hospital
      for tuberculosis (TB) patients. OBJECTIVE: To evaluate the use of personal
      respiratory protection by health care workers (HCWs) as a measure to reduce TB
      occupational risk. DESIGN: One hundred and forty-five HCWs were randomly observed
      for the use of a N95 respirator when entering high-risk areas or performing high
      risk procedures. RESULTS: N95 respirators were infrequently used, even for high
      risk procedures such as endotracheal intubation (25%) and respiratory aspiration
      (12%), and in high-risk areas such as the respirology ward (69.2%), emergency
      department (29.5%), intensive care unit (8.8%), and TB room isolation (39.5%).
      Facial-seal leakage was observed in 39% of HCWs due to failure to wear the mask
      with a tight facial fit as directed. CONCLUSION: Respirator use as a sole control
      measure is inadequate in any setting and is not cost-effective in resource
      limited settings. Alternative or additional measures are clearly needed in
      hospitals with a high incidence of active TB admissions, specially following
      recent recommendations from the WHO, which consider personal respiratory
      protection as the third line of defense for TB control, indicated when TB risk
      cannot be adequately reduced by administrative and engineering controls.

PMID- 15875928
TI  - Tuberculosis education in an endemic setting: application of participatory
      methods to video development in The Gambia.
AB  - OBJECTIVE: To produce an educational video for tuberculosis (TB) awareness in The
      Gambia using participatory methods and integrated formative evaluation. METHODS:
      A steering group was formed of key people working in TB research, health
      education, the health service and the media. They developed a script and
      commissioned local production of the video in three local languages and English.
      A formative participatory evaluation of the project was conducted using document
      review, attendance at rehearsals and semi-structured interviews. A pilot version
      of the video was evaluated through focus groups in Banjul and remote villages.
      Data were analysed using a general inductive approach. RESULTS: Five major themes
      emerged from evaluation of the project participatory process: collaboration,
      knowledge sharing, networking, ownership and a common desire to sustain the
      project goals for video dissemination. The video was well received and described
      as informative, entertaining and professional. Audiences were able to identify
      the key messages, prevailing attitudes about TB were challenged, and many
      participants expressed a desire to act on their new knowledge. CONCLUSION: A
      participatory approach to the development of a video in The Gambia proved to be
      empowering to local participants and led to the production of a resource well
      received by Gambian people.

PMID- 15875929
TI  - Predictors of relapse among pulmonary tuberculosis patients treated in a DOTS
      programme in South India.
AB  - OBJECTIVE: To identify risk factors associated with relapse among cured
      tuberculosis (TB) patients in a DOTS programme in South India. DESIGN: Sputum
      samples collected from a cohort of TB patients registered between April 2000 and
      December 2001 were examined by fluorescence microscopy for acid-fast bacilli and
      by culture for Mycobacterium tuberculosis at 6, 12 and 18 months after treatment
      completion. RESULTS: Of the 534 cured patients, 503 (94%) were followed up for 18
      months after treatment completion. Of these, 62 (12%) relapsed during the 18
      month period; 48 (77%) of the 62 relapses occurred during the first 6 months of
      follow-up. Patients who took treatment irregularly were twice more likely to have
      a relapse than adherent patients (20% vs. 9%; adjusted odds ratio [aOR] 2.5; 95%
      CI 1.4-4.6). Other independent predictors of relapse were initial drug resistance
      to isoniazid and/or rifampicin (aOR 4.8; 95% CI 2.0-11.6) and smoking (aOR 3.1;
      95% CI 1.6-6.0). The relapse rate among non-smoking, treatment adherent patients
      with drug-sensitive organisms was 4.8%. CONCLUSIONS: The relapse rate under the
      DOTS programme may be reduced by ensuring that patients take their treatment
      regularly and are counselled effectively about quitting smoking.

PMID- 15875930
TI  - Every provider counts: effect of a comprehensive public-private mix approach for
      TB control in a large metropolitan area in India.
AB  - SETTING: Mumbai, India. OBJECTIVES: To assess impact on case notification and
      treatment outcome of a public-private mix approach for tuberculosis (TB) control
      involving private providers, non-governmental organisations (NGOs), and public
      providers not previously involved in the Revised National TB Control Programme
      (RNTCP). METHODS: Under the stewardship of the RNTCP, providers were allocated
      different roles in referral, diagnosis, treatment initiation, directly observed
      treatment (DOT) provision, training and supervision. Referral forms were
      introduced and RNTCP registers were adapted to enable monitoring of case
      notification by different providers and cohort analysis disaggregated by provider
      type. RESULTS: A fraction of all non-RNTCP providers had become actively involved
      by the end of 2003. These providers contributed 2145 new smear-positive cases in
      2003, an increment of 40% above the 5397 cases detected in RNTCP facilities. The
      treatment success rate for new smear-positive cohorts for 2002 was 85% in RNTCP
      facilities, 81% in private clinics, 88% in medical colleges, 91% in NGOs and 73%
      in the TB hospital (where the death rate was 16%). CONCLUSION: Active involvement
      of some key public and private providers can increase case notification
      substantially while maintaining acceptable treatment outcomes. The impact can be
      expected to be even larger when all health providers have been involved.

PMID- 15875931
TI  - Annual risk of tuberculous infection in four defined zones of India: a
      comparative picture.
AB  - SETTING: Twenty-six selected districts in India. OBJECTIVES: To estimate the
      average annual risk of tuberculous infection (ARTI) in four defined zones in the
      country. STUDY DESIGN: A tuberculin survey was conducted in selected clusters of
      26 districts in four defined zones of India. Children 1-9 years of age were
      subjected to tuberculin testing with ITU PPD RT23 with Tween 80, and the maximum
      transverse diameter of induration was measured 72 h later. Prevalence of
      infection was estimated using the cut-off point method (Method I) and the mirror
      image technique (Method II) among children without bacille Calmette-Guerin scar.
      Results from individual zones have been reported earlier, and the results from
      all four zones are presented here as a consolidated summary. RESULTS: The ARTI
      computed from estimated prevalence was found to be lowest in the southern zone
      (Method I: 1.1%, Method II: 1.0%). It was higher in the eastern zone (1.3% by
      both methods) and highest in the western (Method I: 1.8%, Method II: 1.6%) and
      northern zones (1.9% by both methods). The proportion of infected children was
      found to be significantly higher in urban than in rural areas in all zones.
      CONCLUSION: The intensified tuberculosis control efforts need to be sustained for
      many years.

PMID- 15875932
TI  - Restriction fragment length polymorphism study of nationwide samples of
      Mycobacterium tuberculosis in Thailand, 1997-1998.
AB  - SETTING: During 1997-1998, a national anti-tuberculosis drug resistance survey
      was conducted in Thailand as a part of a global project. OBJECTIVE: To evaluate
      the IS6110 hybridisation patterns and the level of clustering, which was expected
      to be low due to the short duration of the sample collection. DESIGN: Eight
      hundred and twenty-eight bacterial isolates were available for fingerprinting by
      standard IS6110 hybridisation. RESULTS: The restriction fragment length
      polymorphism patterns varied with geographic locations, ages of the patients, and
      resistance to rifampicin and streptomycin. The Beijing strain was more common
      among younger patients, and their prevalence appeared to decrease with the
      distance from Bangkok, while the opposite was true for the single-banded
      isolates. Excluding isolates containing five or less copies of IS6110, 26.4% were
      clustered. Clustering was more common among females. The clustered isolates were
      sometimes from different provinces and, if resistant to drugs, usually possessed
      different resistance profiles. CONCLUSIONS: The results question the validity of
      inferring recent transmission from the clustering of IS6110 hybridisation
      patterns in some settings in Thailand. The level of recent transmission in a
      nationwide study in a country with a high incidence of tuberculosis should be
      evaluated with caution.

PMID- 15875933
TI  - Scaling up HIV/AIDS and joint HIV-TB services in Malawi.
AB  - Two country-wide surveys were undertaken to assess progress in scaling up human
      immunodeficiency virus/ acquired immune-deficiency syndrome (HIV/AIDS) and HIV
      tuberculosis (TB) services in the public health sector in Malawi between 2002 and
      2003. In 2003, 118 sites were performing counselling and HIV testing compared
      with 70 in 2002. There were 215 269 HIV tests carried out in 2003 compared with
      149 540 in 2002, the largest increases being in pregnant women (from 5059 to
      26791), patients with TB (from 2130 to 3983) and patients/clients attending
      health facilities (from 35 407 to 79 584). In 2003, 3703 patients with AIDS were
      started on antiretroviral therapy compared with 1220 patients in 2002.

PMID- 15875934
TI  - Optimal utility of TB medicines by any patient.

PMID- 15875935
TI  - Hospital doctors' and nurses' knowledge of how to use inhalation devices
      correctly.

PMID- 15875936
TI  - DOTS: necessary but sufficient.

PMID- 15875937
TI  - [The peculiarities of stability of vertical posture in patients with segmental
      lesions of the spinal cord].
AB  - Using computer stabilography, vertical posture has been studied in 3 groups of
      children and adolescences with traumatic lesion of the spinal cord after surgery
      of congenital myelocele (n=10) and myelodysplasia (n=10) and in 124 healthy
      controls. Also, an extent of segmental lesions was investigated by
      electroneuromyography of lower extremities muscles. Patients with pronounced
      segmental lesion had small-amplitude, -velocity and -frequency variations of body
      center of gravity (BCG) during standing with visual control. After excluding
      visual control of vertical posture, there was a significant decrease of vertical
      stability that suggests a relevant role of visual analyzer in the control of
      vertical posture. In patients with minor segmental lesion, BCG variations of
      small amplitude, velocity and frequency were observed. Exclusion of visual
      control did not result in significant reduction of vertical stability. It is
      concluded that stabilographic survey is an objective method for diagnosis of an
      extent of segmental lesion of the spinal cord.

PMID- 15875938
TI  - [Psychological mechanisms of refusal reactions in schizophrenic patients].
AB  - The psychological study is based on the clinical typology of refusal reactions
      (RR) in schizophrenic patients--"capitulation", "avoidance", "absenteism".
      Seventy patients with RR, mean age 27 years, 25 women, 45 men, were examined with
      the use of a number of psychological methods. The findings prove the hypothesis
      on the disturbances of motivation as a psychological mechanism of RR in
      schizophrenic patients. Deficiency is related to functions of the motivational
      process: incentive function, goal achievement, sense making and strengthened by
      trait anxiety and desize to avoid danger. The main factor promoting RR formation
      is basic motivation deficiency caused by endogenous process (schizophrenia). A
      mechanism of capitulation reaction formation is closely related to expectation of
      failure and refusal from acting as an opportunity to preserve self-estimation;
      avoidance reaction is characterized by significant disturbance of the motivation
      at the stage of incentive, goal achievement and sense making. Motivation
      deficiency in patients with absenteism reactions is predominantly associated with
      an specific individual's sense.

PMID- 15875939
TI  - [Functional brain activity in patients with Parkinson's disease during amantadin
      sulfate therapy].
AB  - An investigation of bioelectrical brain activity in 32 patients with akinetic
      rigid and trembling-rigid forms of Parkinson's disease was conducted before and
      after treatment with amantadin-sulfate on the basis of spectral-coherent EEG
      analysis. Comparing to controls, EEG deviations, mainly related to the main
      rhythm, were observed in 93.75% patients. Symptoms stabilization augmented EEG
      disorganization emerging in diffused spikes and sharp theta- and alpha-waves. The
      presence of paroxysmal activity in the form of synchronic bilateral groups of
      theta-waves and/or beta-waves was detected in 11 out of 32 patients, with
      paroxysmal activity of theta-waves being more evident in patients with a
      trembling PD form. In the group of patients with post treatment positive
      dynamics, EEG spectrum power increased in the range of alpha-beta-waves.
      Significant differences were mainly found in the range of beta-activity in
      frontal-parietal-occipital leads of the left hemisphere. The coherent analysis of
      EEG revealed that an amantadin-sulfate course resulted in normalization of space
      organization of biopotentials at the expense of a decrease of pathologically high
      indications of coherency for the majority of intra- and interhemisphere pairs of
      leads in alpha-, beta- and theta-ranges. In those regions, where the spectrum
      power increased in the same range, a significant decrease of the coherency
      indices was detected for inter hemispheric frontal-frontal, frontal-parietal and
      frontal-occipital leads and intracortical long connections of the left
      hemisphere. In amantadin-sulfate non-responders, the changes of EEG spectrum and
      coherency were insignificant.

PMID- 15875940
TI  - [The use of valproates-generics in the treatment of epileptic patients].
AB  - Therapeutic efficacy, adverse effects, cost efficacy of Encorate chrono (generics
      of Depakine chrono) as well as impact on quality of life have been studied in 36
      patients with symptomatic and idiopathic epilepsy and different types of
      seizures. For all parameters, Encorate-chrono was as effective as the original
      drug. It may be recommended for patients with epilepsy with generalized and
      partial seizures as an equal analogue of Depakine in case of its absence.

PMID- 15875941
TI  - [Aphobazol--new selective anxyolytic drug].
AB  - A standardized clinical and pharmacological trial of the peculiarities of action
      and efficacy of aphobazol, a new anxyolytic with non-benzodiazepine structure,
      has been conducted. An effect of the drug on different anxiety disorders has been
      studied. It is shown that combined anxyolytic and activating action exerted the
      main effect. The best efficacy of aphobazol was found in anxiety disorders of
      "simple" structure. In more complicated anxiety disorders, aphobazol efficacy
      depended on the correlation between clinical appearances of deeper registers and
      anxiety affect. The best results have been achieved in patients with acute
      anxiety-phobic disorders, in the structure of which sensible anxiety with
      episodes of generalization, dominating vivid ideas, sensibly saturated phobias
      with pronounced autonomic disorders and senestalgias prevailed. In case of
      chronic disease course, with formation of more inert, "complex" in structure and
      deep by register psychopathological disorders (cognitive character of anxiety,
      appearances of agoraphobia and avoidance behavior, heteronomous body sensations
      and hypochondriac activity), the efficacy of aphobazol treatment was
      significantly lower. In this case a therapy combined with selective inhibitors of
      serotonin reuptake and neuroleptics is needed.

PMID- 15875942
TI  - [An impact of pronoran on cognitive and affective disorders in Parkinson's
      disease].
AB  - Sixty patients with different types of Parkinson's disease (PD), the disease
      stage 2.3 +/- 0.08 according to Hoehn&Yahr scale, were treated with Pronoran.
      Impact of the drug on movement, cognitive and affective disorders assessed by
      corresponding scales and psychological tests has been studied. Pronoran exerted a
      positive effect on all the disorders. It improved cognitive function, i.e.
      reasoning, memory and attention. A more pronounced influence on cognitive
      function was detected in earlier stages of the disease and for less severity
      cases of rigid-tremor PD type. A moderate antidepressive effect of Pronoran was
      found, being more pronounced in the severe PD stages. Emotional disorders were
      better treated, when Pronoran was used in combination with madopar, and cognitive
      dysfunction--in case of monotherapy.

PMID- 15875943
TI  - [The influence of tumor necrosis factor alpha on the processes of sphingomyelin
      cycle and lipid peroxidation in brain].
AB  - The influence of tumor necrosis factor alpha (TNF-alpha) on the processes of
      sphingomyelin cycle activation and intensity of peroxidation in animal brain in
      vivo has been studied. Alterations in activity of sphingomyelinase, a key
      sphingomyelin cycle enzyme and in sphingomyelin, ceramide content as well as
      accumulation of the products of lipid peroxidation (diene conjugates and diene
      ketons) were measured in the cortex, the cerebellum and the hippocampus of rats
      5, 15, 30 min, 1, 2 and 5 hours after TNF-alpha intraperitoneal injection in
      dosage 100 mkg per animal. It is shown that 2 hours after the injection, TNF
      alpha initiated an accumulation of the products of lipid peroxidation, which
      intensively developed in the cerebellum and the hippocampus. Sphingomyelinase
      activation was found in the same brain structures. At the initial stage of TNF
      alpha action, an increase of lipid peroxidation products correlated with
      sphingomyelinase activation in the cerebellum and the hippocampus suggesting an
      interaction of two cell signal systems of sphingomyelin cycle and oxidative
      system.

PMID- 15875944
TI  - [Concentration and protein composition of circulating immune complexes in the
      blood of patients with schizophrenia and subjects with positive familial history
      of disease].
AB  - A comparative study of blood serum concentrations and pathogenic properties of
      circulating immune complexes (CIC), along with identification of their protein
      composition, was conducted in 45 patients with schizophrenia, 15 their healthy
      relatives and 39 normal controls. In patients and their relatives, mean
      concentration of small CIC was within the normal range, while concentrations of
      giant, large and middle CIC were higher than those of the controls (p<0.001).
      Over 80% of schizophrenic patients and their relatives had pathogenic immune
      complexes in the circulation. Clinical and immunologic analysis of patients with
      schizophrenia revealed a correlation between the illness duration and CIC
      concentration for all sizes. Smokers had significantly lower levels of small CIC
      comparing to non-smokers. Determination of CIC composition in patients and
      relatives revealed a presence of specific proteins in the immune complexes with
      molecular weights of 36 and 25 kDa. The results suggest genetic determination of
      autoimmune processes in schizophrenia.

PMID- 15875945
TI  - [Estimation of activity and prospective development of psychiatric services on
      the basis of hierarchic model principles].

PMID- 15875946
TI  - [Molecular mechanisms of motor neuron disease].

PMID- 15875949
TI  - Managing insulin requirements at school.

PMID- 15875950
TI  - Are there fakes and frauds in your nebulizer?
AB  - As patient advocates and educators, Allergy and Asthma Network Mothers of
      Asthmatics is concerned with the safety and quality of respiratory medications in
      our country. As such, we've formed CHASM, the Consumer Health Alliance for Safe
      Medications. This is the first in a series of articles looking at this topic.

PMID- 15875951
TI  - Reducing risk liability for dental injuries in school children.

PMID- 15875952
TI  - Eating disorders: early detection can lead to improved outcomes.

PMID- 15875953
TI  - Culturally competent care for school nurses.

PMID- 15875954
TI  - Self mutilation: inward pain turned inside out.

PMID- 15875955
TI  - What's new in the treatment and management of food allergy.

PMID- 15875956
TI  - "If you want to win, you have to learn to get along:" youth talk about their
      participation in extracurricular activities.

PMID- 15875957
TI  - Reintegrating the mind and body.

PMID- 15875958
TI  - Parental presence during anesthesia induction in children.
AB  - Family-centered care has become a popular topic in pediatric nursing and,
      therefore, is becoming an important part of both nursing anesthesia and
      perioperative nursing. Currently, few hospitals involve parents in pediatric
      surgery, even though the presence of a parent for pediatric anesthesia induction
      is strongly supported in the literature. This article reviews the literature
      regarding the effect on children and parents of parental presence during
      induction of pediatric anesthesia. Suggestions for appropriate parent-preparation
      techniques also are provided.

PMID- 15875959
TI  - Educating perioperative managers about materials and financial management.
AB  - One of the most resource intensive areas in many hospitals is the OR, which often
      accounts for more than 50% of a hospital's materials management budget. Surgical
      services managers often have no formal training in materials and financial
      management, but they are held accountable for one of the most costly clinical
      areas in the hospital. A program proposed for Navy perioperative nurse managers
      is a five-day course that covers the basics of Navy medical materials and
      financial management as they apply to the OR. Application strategies for the
      civilian sector also are discussed.

PMID- 15875960
TI  - Heel calf capillary-support pressure in lithotomy positions.
AB  - A three-part analysis was undertaken to increase understanding of the occurrence
      of pressure ulcers in lithotomy positions. An innovative measuring device was
      used to determine capillary pressure. Ankle blood pressure was measured compared
      to ankle height in 11 participants. Ankle systolic and diastolic pressure
      decreased approximately 20 mmHg per foot of elevation. Calf and heel capillary
      support pressures were measured in 15 participants in the standard lithotomy
      position. Capillary-support pressure for the calf was substantially less than for
      the heel. Heel capillary-support pressures were measured in 16 participants in
      the high lithotomy position. As heel height increased, capillary-support pressure
      also increased.

PMID- 15875961
TI  - The effect of a preadmission videotape on patient satisfaction.
AB  - The effect of a preadmission videotape presentation on patient satisfaction in an
      outpatient surgery department was explored in this research study. A sample of
      141 Caucasian and Hispanic patients took part in the study. Results indicated
      that patients who viewed the preadmission patient videotape did not differ
      significantly in their report of satisfaction from those who did not view the
      videotape. The study also found that the satisfaction of nurses in the project
      varied significantly during the study period.

PMID- 15875962
TI  - Update on KEYS to patient safety and public policy.

PMID- 15875963
TI  - Recommended practices for cleaning, handling and processing anesthesia equipment.

PMID- 15875964
TI  - AORN Guidance Statement: preoperative patient care in the ambulatory surgery
      setting.

PMID- 15875965
TI  - AORN Guidance Statement: postoperative patient care in the ambulatory surgery
      setting.

PMID- 15875966
TI  - Best practices for safe medication administration.

PMID- 15875967
TI  - Common and distinctive features in stimulus similarity: a modified version of the
      contrast model.
AB  - Featural representations of similarity data assume that people represent stimuli
      in terms of a set of discrete properties. In this article, we consider the
      differences in featural representations that arise from making four different
      assumptions about how similarity is measured. Three of these similarity models-
      the common features model, the distinctive features model, and Tversky's seminal
      contrast model-have been considered previously. The other model is new and
      modifies the contrast model by assuming that each individual feature only ever
      acts as a common or distinctive feature. Each of the four models is tested on
      previously examined similarity data, relating to kinship terms, and on a new data
      set, relating to faces. In fitting the models, we have used the geometric
      complexity criterion to balance the competing demands of data-fit and model
      complexity. The results show that both common and distinctive features are
      important for stimulus representation, and we argue that the modified contrast
      model combines these two components in a more effective and interpretable way
      than Tversky's original formulation.

PMID- 15875968
TI  - The role of response mechanisms in determining reaction time performance:
      Pieron's law revisited.
AB  - A response mechanism takes evaluations of the importance of potential actions and
      selects the most suitable. Response mechanism function is a nontrivial problem
      that has not received the attention it deserves within cognitive psychology. In
      this article, we make a case for the importance of considering response mechanism
      function as a constraint on cognitive processes and emphasized links with the
      wider problem of behavioral action selection. First, we show that, contrary to
      previous suggestions, a well-known model of the Stroop task (Cohen, Dunbar, &
      McClelland, 1990) relies on the response mechanism for a key feature of its
      results-the interference-facilitation asymmetry. Second, we examine a variety of
      response mechanisms (including that in the model of Cohen et al., 1990) and show
      that they all follow a law analogous to Pieron's law in relating their input to
      reaction time. In particular, this is true of a decision mechanism not designed
      to explain RT data but based on a proposed solution to the general problem of
      action selection and grounded in the neurobiology of the vertebrate basal ganglia
      Finally, we show that the dynamics of simple artificial neurons also support a
      Pieron-like law.

PMID- 15875969
TI  - An evaluation of dual-process theories of reasoning.
AB  - Current theories propose that reasoning comprises two underlying systems (Evans &
      Over, 1996; Sloman, 1996; Stanovich & West, 2000). The systems are identified as
      having functionally distinct roles, differ according to the type of information
      encoded, vary according to the level of expressible knowledge, and result in
      different responses. This article evaluates the arguments and the evidence from a
      select number of key tasks that have been supportive of dual-reasoning theorists'
      proposals. The review contrasts the dualist approach with a single-system
      framework that conjectures that different types of reasoning arise through the
      graded properties of the representations that are utilized while reasoning, and
      the different functional roles that consciousness has in cognition. The article
      concludes by arguing in favor of the alternative framework, which attempts to
      unify thedifferent forms of reasoning identified by dual-process theorists under
      a single system.

PMID- 15875970
TI  - The cognitive neuroscience of creativity.
AB  - This article outlines a framework of creativity based on functional neuroanatomy.
      Recent advances in the field of cognitive neuroscience have identified distinct
      brain circuits that are involved in specific higher brain functions. To date,
      these findings have not been applied to research on creativity. It is proposed
      that there are four basic types of creative insights, each mediated by a
      distinctive neural circuit. By definition, creative insights occur in
      consciousness. Given the view that the working memory buffer of the prefrontal
      cortex holds the content of consciousness, each of the four distinctive neural
      loops terminates there. When creativity is the result of deliberate control, as
      opposed to spontaneous generation, the prefrontal cortex also instigates the
      creative process. Both processing modes, deliberate and spontaneous, can guide
      neural computation in structures that contribute emotional content and in
      structures that provide cognitive analysis, yielding the four basic types of
      creativity. Supportive evidence from psychological, cognitive, and
      neuroscientific studies is presented and integrated in this article. The new
      theoretical framework systematizes the interaction between knowledge and creative
      thinking, and how the nature of this relationship changes as a function of domain
      and age. Implications for the arts and sciences are briefly discussed.

PMID- 15875971
TI  - Semantic generalization of stimulus-task bindings.
AB  - People find it difficult to switch between two tasks, even if they have time to
      prepare-the so-called residual task shift cost. We studied a switch of tasks from
      picture naming to word reading, using picture-word Stroop stimuli. Consistent
      with previous findings, we demonstrate that a large part of the observed task
      shift cost was due to priming from prior stimulus-response episodes, in which the
      current task stimulus was encountered in a competing task. We further show that
      this task-priming effect generalizes to semantically related stimuli, which opens
      the possibility that most or all of these residual shift costs reflect some sort
      of generalized proactive interference from previous stimulus-task episodes.

PMID- 15875972
TI  - Inhibiting prepared and ongoing responses: is there more than one kind of
      stopping?
AB  - Inhibiting movements has been investigated widely using the countermanding (stop
      signal) paradigm. Although it has been assumed that response inhibition, as
      measured by the countermanding task, generalizes to all forms of stopping, this
      has never been tested. In the present study, stopping performance in the
      countermanding paradigm was compared with stopping performance in a new paradigm
      in which a continuous-tracking task was used. Although stimulus presentations
      were matched across paradigms, the two tasks differed in the type of stopping
      required. In the countermanding paradigm, response inhibition latency was
      measured prior to response execution-this is, it was inferred from the successful
      withholding of a go response. In the new paradigm, response inhibition was
      carried out after response execution-that is, it was measured as the time to
      begin stopping a continuous tracking response. Results indicated that stopping
      latencies between the two paradigms were highly correlated, providing strong
      evidence that stopping an unexecuted response engages the same mechanisms as
      stopping an ongoing response.

PMID- 15875973
TI  - Confidence and gradedness in semantic categorization: definitely somewhat
      artifactual, maybe absolutely natural.
AB  - Artifacts tend to be categorized in a graded (i.e., continuous) manner, whereas
      natural categorization tends to be absolute (i.e., discrete). This domain
      specific categorization is assumed to reflect a domain difference in
      representation. However, another tenable but untested explanation is that graded
      categorization arises from uncertainty, which is greater in artifact categories
      than in natural categories. Confidence ratings were used as an index of certainty
      in two experiments that tested whether confidence in category judgments can
      explain the apparent gradedness of those categories. Both experiments revealed
      that artifact categories were more graded and were judged with greater confidence
      than were natural categories. Confidence and gradedness were negatively
      correlated within both domains. Thus, confidence did indeed predict gradedness
      within the artifact and natural domains but failed to predict the difference in
      gradedness between those domains. There is more to gradedness than just
      uncertainty.

PMID- 15875974
TI  - Is categorization performance really intact in amnesia? A meta-analysis.
AB  - Most published studies of category learning in amnesia have reported intact
      categorization performance. These results have been used to challenge single
      system accounts of categorization and recognition, in which a single
      representational system mediates performance in these two tasks. Many of the
      published studies, however, have shown a numerical advantage for controls over
      amnesics and often have had low statistical power. A meta-analysis was conducted
      to assess whether this numerical advantage is significant when the data are
      pooled across studies. This analysis indicates that amnesic subjects do, in fact,
      show deficits in categorization tasks, which is consistent with single-system
      exemplar model predictions.

PMID- 15875975
TI  - The affective consequences of visual attention in preview search.
AB  - Comparisons of emotional evaluations of abstract stimuli just seen in a two
      object visual search task show that prior distractors are devalued, as compared
      with prior targets or novel items, perhaps as a consequence of persistent
      attentional inhibition (Raymond, Fenske, & Tavassoli, 2003). To further explore
      such attention-emotion effects, we measured search response time in a preview
      search task and emotional evaluations of colorful, complex images just seen
      therein. On preview trials, the distractors appeared 1,000 msec before the
      remaining items. On no-preview trials, all the items were presented
      simultaneously. A single distractor was then rated for its emotional tone.
      Previewed distractors were consistently devalued, as compared with nonpreviewed
      distractors, despite longer exposure and being associated with an easier task.
      This effect was observed only in the participants demonstrating improved search
      efficiency with preview, but not in others, indicating that the attentional
      mechanisms underlying the preview benefit have persistent affective consequences
      in visual search.

PMID- 15875977
TI  - Older adults' associative deficit in episodic memory: assessing the role of
      decline in attentional resources.
AB  - In this study, we evaluated an associative deficit hypothesis. This hypothesis
      suggests that the deficit seen in the episodic memory performance of older adults
      is due, in considerable part, to older adults' difficulty in binding together
      unrelated components of an episode into a cohesive entity (Naveh-Benjamin, 2000).
      The study extended the conditions under which older adults show a differential
      deficit in tests requiring associations among the episode components to
      situations in which the item and the associative recognition tests are equated on
      the response mode used and on the amount of information displayed. In addition,
      we tested the potential role of a decrease in attentional resources in the
      associative deficit of older adults by comparing their performance to that of
      younger adults under conditions of reduced attentional resources. The results of
      the study, which indicate that younger adults under divided attention do not show
      an associative deficit, are interpreted as indicating that the associative
      deficit of older adults is due to factors other than depleted attentional
      resources.

PMID- 15875976
TI  - Strong memories obscure weak memories in associative recognition.
AB  - The list strength effect, in which strengthening some memories has a detrimental
      effect on the retrieval of other memories, has generally not been found in item
      recognition. The present study shows that the list strength effect does occur in
      associative recognition. Study materials were sets of overlapping word pairs (A
      B, A-C, D-B, etc.). Within critical sets of words, strong pairs were presented
      three times at study, as compared with one presentation for weak pairs. In
      Experiment 1, associative recognition for weak pairs was less accurate than that
      for baseline pairs, and response times for hits were slower. In Experiment 2,
      receiver-operating characteristic curve data provided further evidence of poor
      accuracy for weak pairs. These findings support a qualitative distinction between
      item and associative recognition.

PMID- 15875978
TI  - Item-specific processing reduces false memories.
AB  - We examined the effect of item-specific and relational encoding instructions on
      false recognition in two experiments in which the DRM paradigm was used (Deese,
      1959; Roediger & McDermott, 1995). Type of encoding (item-specific or relational)
      was manipulated between subjects in Experiment 1 and within subjects in
      Experiment 2. Decision-based explanations (e.g., the distinctiveness heuristic)
      predict reductions in false recognition in between-subjects designs, but not in
      within-subjects designs, because they are conceptualized as global shifts in
      decision criteria. Memory-based explanations predict reductions in false
      recognition in both designs, resulting from enhanced recollection of item
      specific details. False recognition was reduced following item-specific encoding
      instructions in both experiments, favoring a memory-based explanation. These
      results suggest that providing unique cues for the retrieval of individual
      studied items results in enhanced discrimination between those studied items and
      critical lures. Conversely, enhancing the similarity of studied items results in
      poor discrimination among items within a particular list theme. These results are
      discussed in terms of the item-specific/ relational framework (Hunt & McDaniel,
      1993).

PMID- 15875979
TI  - Collaborative inhibition is due to the product, not the process, of recalling in
      groups.
AB  - When people remember together, they recall less than if they remembered
      separately. This is called collaborative inhibition. We examine whether this is
      due to the product of group recall or the process of recalling in groups. In
      other words, is it what the other people recall or the structure of the group
      dialogue that impairs group performance? Participants worked either independently
      or in pairs. For half of the pairs, the participants saw the items that the other
      person recalled. As was expected, this led to levels of recall that were lower
      than those for the control participants. For the other half of the pairs, the
      participants did not see the words recalled by the other person but still
      followed a turn-taking protocol. Recall was at the level of that in the nominal
      control condition. Collaborative inhibition is due to interference caused by the
      product of recall, not the process.

PMID- 15875980
TI  - It's not what you hear but how often you hear it: on the neglected role of
      phonological variant frequency in auditory word recognition.
AB  - Recognition of a frequently heard spoken word variant in American English
      (flapping) was investigated in a phoneme identification experiment. Listeners
      identified the initial segment (b or p) of word-nonword continua (e.g., pretty
      bretty) that was embedded in either a flap or a [t] variant carrier word (e.g.,
      preDy-breDy or preTTy-breTTy). The results showed more identification responses
      forming a real word when the to-be-identified speech sound occurred in the more
      frequently experienced flap carrier. These results support the claim that lexical
      representation of spoken words includes the flap variant. Listeners do not recode
      the flap variant into an underlying /t/ version but recognize the flap, in its
      surface form, via a preexisting representation in lexical memory.

PMID- 15875981
TI  - The broth in my brother's brothel: morpho-orthographic segmentation in visual
      word recognition.
AB  - Much research suggests that words comprising more than one morpheme are
      represented in a "decomposed" manner in the visual word recognition system. In
      the research presented here, we investigate what information is used to segment a
      word into its morphemic constituents and, in particular, whether semantic
      information plays a role in that segmentation. Participants made visual lexical
      decisions to stem targets preceded by masked primes sharing (1) a semantically
      transparent morphological relationship with the target (e.g., cleaner-CLEAN), (2)
      an apparent morphological relationship but no semantic relationship with the
      target (e.g., corner-CORN), and (3) a nonmorphological form relationship with the
      target (e.g., brothel-BROTH). Results showed significant and equivalent masked
      priming effects in cases in which primes and targets appeared to be
      morphologically related, and priming in these conditions could be distinguished
      from nonmorphological form priming. We argue that these findings suggest a level
      of representation at which apparently complex words are decomposed on the basis
      of their morpho-orthographic properties. Implications of these findings for
      computational models of reading are discussed.

PMID- 15875982
TI  - Causal models frame interpretation of mathematical equations.
AB  - We offer evidence that people can construe mathematical relations as causal. The
      studies show that people can select the causal versions of equations and that
      their selections predict both what they consider most understandable and how they
      expect variables to influence one another. When asked to write down equations,
      people have a strong preference for the version that matches their causal model.
      Causal models serve to structure equations by determining the preferred order of
      variables: Causes should be on one side of an equality, and a single effect
      should appear on the other.

PMID- 15875983
TI  - Is stimulus competition an acquisition deficit or a performance deficit?
AB  - Traditionally, blocking (X-outcome, followed by XY-outcome, resulting in
      attenuated conditioned responding to Y, relative to XY-outcome alone) has been
      explained in terms of the X-outcome association's preventing the acquisition of
      the Y-outcome association. This view is challenged by models that view stimulus
      competition as a deficit in the expression of the acquired Y-outcome association.
      Here, we provide evidence that blocking is a performance deficit in which the Y
      outcome association, the to-be-blocked stimulus, can affect behavioral control by
      the blocking stimulus (i.e., attenuate responding to X). The results are
      discussed in terms of acquisition and performance models of stimulus competition.

PMID- 15875984
TI  - Pigeons concurrently categorize photographs at both basic and superordinate
      levels.
AB  - We studied categorization in pigeons, using carefully controlled photographs.
      Within daily sessions, 4 pigeons had to classify each of 32 photographs into
      either its proper basic-level category (cars, chairs, flowers, or people; four
      key forced choice procedure) or its proper superordinate-level category (natural
      or artificial; two-key forced choice procedure). The pigeons successfully
      classified the same stimuli at both levels. Overall, the pigeons learned the
      basic discrimination more quickly than the superordinate discrimination, but this
      difference was reliable only for artificial stimuli (cars and chairs), not for
      natural stimuli (flowers and people). The pigeons also exhibited reliable
      discrimination transfer to novel photographs, attesting to the open-endedness of
      these basic and superordinate categories.

PMID- 15875985
TI  - Differential reinstatement predicted by preextinction response rate.
AB  - Reinstatement refers to the recovery of previously extinguished responding by the
      response-independent delivery of a stimulus that was a reinforcer in training.
      Two experiments were conducted to examine relative reinstatement following the
      training of differential preextinction response rates, either with equal
      (Experiment 1) or unequal (Experiment 2) preextinction reinforcement rates. In
      Experiment 1, each of 3 pigeons first pecked at relatively high rates in the
      tandem variable-time 117-sec fixed-interval 3-sec component of a multiple
      schedule and at lower rates in a separate tandem variable-interval 117-sec fixed
      time 3-sec component. Reinforcement rates were equal between components. Pecking
      then was extinguished in each component, before being reinstated under a multiple
      variable-time 120-sec variable-time 120-sec schedule. Greater reinstatement
      occurred in the component previously correlated with higher rates of pecking. In
      Experiment 2, in an initial condition, the mean rate of lever pressing for one
      group of 8 rats was significantly higher under a fixed-ratio 3 schedule than for
      another group of 8 rats under a fixed-ratio 1 schedule. Mean reinforcement rate
      was significantly higher for the group exposed to the fixed-ratio 1 schedule. For
      each group, lever pressing then was extinguished, before being reinstated under a
      variable-time 30-sec schedule. Significantly greater mean reinstatement occurred
      for the group previously exposed to the fixed-ratio 3 schedule. These results
      suggest that differential reinstatement may be predicted by preextinction
      response rate, perhaps independently of preextinction reinforcement rate.

PMID- 15875986
TI  - The rich get richer: students' discounting of hypothetical delayed rewards and
      real effortful extra credit.
AB  - The present research compared choices among students with higher or lower grades
      for rewards that were devalued by imposing a delay to their receipt (Study 1) or
      by requiring more work for a larger reward (Study 2). In Study 1, students chose
      between hypothetical and noncontingent smaller immediate or larger delayed
      monetary rewards. In Study 2, students chose from among different amounts of
      real, response-contingent academic rewards (extra credit) that required different
      amounts of work. The results of both studies were similar: The highest scoring
      students discounted the value of the delayed money less than did their lower
      scoring counterparts, and the highest scoring students also chose to do and
      actually did more extra-credit work than lower scoring students did. Differences
      in the discounting of devalued rewards might represent a fundamental difference
      between the highest and lower scoring students.

PMID- 15875987
TI  - Predicting true patterns of cognitive performance from noisy data.
AB  - Starting from the premise that the purpose of cognitive modeling is to gain
      information about the cognitive processes of individuals, we develop a general
      theoretical framework for assessment of models on the basis of tests of the
      models' ability to yield information about the true performance patterns of
      individual subjects and the processes underlying them. To address the central
      problem that observed performance is a composite of true performance and error,
      we present formal derivations concerning inference from noisy data to true
      performance. Analyses of model fits to simulated data illustrate the usefulness
      of our approach for coping with difficult issues of model identifiability and
      testability.

PMID- 15875988
TI  - Board tries to revoke status.

PMID- 15875989
TI  - Is the worst yet to come? 'Cover the Uninsured Week' will kick off with the
      number of uninsured increasing and fewer employers covering their workers.
AB  - Cover the Uninsured Week will kick off on May 1, with the number of uninsured set
      to grow another 25% through 2013, reaching 56 million Americans. With fewer
      employers willing to provide coverage to their employees, many fear the problem
      will get worse before it gets better. Richard Kronick, left, a professor at the
      University of California at San Diego, says we're no better off than we were 10
      years ago.

PMID- 15875990
TI  - Somber CHC reception. Increased funding appreciated, but still not enough.

PMID- 15875991
TI  - Who's in charge here? Survey reveals much confusion over IT responsibility.

PMID- 15875992
TI  - In or out? JCAHO head gives conflicting retirement statements.

PMID- 15875993
TI  - Lonely at the top. ACHE survey reveals CEO turnover up in 2004.

PMID- 15875994
TI  - HSAs may hurt more than help.

PMID- 15875995
TI  - Staph changes. Providers reassess treatments for infections.

PMID- 15875996
TI  - Exploring alternatives. VHA, UHC may divest their combined majority ownership of
      Neoforma.

PMID- 15875997
TI  - Consultant consolidation. Accenture, Navigant in acquisition mode.

PMID- 15875998
TI  - Deal breaker? Calif. Blues plan investigated for violating deal.

PMID- 15875999
TI  - Standing dispute. CON reversal sought for open hospital.

PMID- 15876000
TI  - The Alabama shuffle. HealthSouth to sell medical center to UAB system.

PMID- 15876001
TI  - The best intentions on access. Efforts to help the uninsured are overwhelmed by
      costs and cutbacks.

PMID- 15876002
TI  - A retro disease on the loose. Rise of hepatitis C in prisons may fuel outbreak in
      general population.

PMID- 15876003
TI  - Leaders in self-improvement. Solucient's annual roster of most improved hospitals
      shows communication, teamwork among keys to financial, operational success.

PMID- 15876004
TI  - Whiz kid goes to Washington. Jindal is ready to help set the healthcare agenda in
      Congress after making a big mark in Louisiana.

PMID- 15876005
TI  - Straight talk--new approaches in healthcare. The best starting point for
      performance improvement: a healthy bottom line. Panel discussion.
AB  - Bon Secours Health System's South Division launched a multitude of performance
      improvement projects in 2004 even though it boasted a 9% margin. Why? Officials
      at the Catholic healthcare system wanted to increase the amount of money
      available for its nation-wide charitable commitments as well as to invest in
      capital projects critical to its mission. In this installment of Straight Talk,
      we look at the performance-improvement initiatives of the South Division of Bon
      Secours Health System, Inc., which saved $8 million in just five months and
      expects to gain a total of $41 million after it completes all projects. Modern
      Healthcare and PricewaterhouseCoopers present Straight Talk. The session on
      performance improvement was held on March 22, 2005 at Modern Healthcare's Chicago
      headquarters. Fawn Lopez, publisher of Modern Healthcare, was the moderator.

PMID- 15876006
TI  - Cost-effectiveness of clopidogrel.

PMID- 15876007
TI  - Changing health environment: the challenge to demonstrate cost-effectiveness of
      new compounds.
AB  - With the development and introduction of costly new technologies and restrictive
      drug budgets, health economic evaluation has gained increasing importance. Health
      economic evaluation is now mandatory as part of reimbursement decisions in many
      countries. Cost-effectiveness analysis, which relates to a defined alternative
      and indication, and for a specific patient group and specific perspective, is the
      preferred health economic analysis used to make valued judgements about the
      efficiency of a new treatment. The costs of the new treatment are assessed
      relative to its potential benefits in terms of improved health, measured as
      increased survival and impact on quality of life. The cost per quality-adjusted
      life-year (QALY), an index combining quality of life and length of life,
      facilitates comparisons between treatments for different diseases. Governments
      are increasingly using QALYas an outcome measure in economic evaluation. The QALY
      provides an estimate, which is then used to make a decision dependent on the
      willingness to pay for the treatment, based on a certain threshold value. Current
      thresholds, usually in the range of approximately US dollars 50000 a year
      (comparable with the annual cost of renal dialysis), vary between different
      countries. However, these thresholds are not absolute limits; choices about the
      allocation of healthcare resources are also influenced by other factors,
      including considerations of equity and the severity of the disease.

PMID- 15876008
TI  - The burden of coronary, cerebrovascular and peripheral arterial disease.
AB  - Atherothrombosis is a potentially life-threatening generalised disease process
      that affects the coronary, cerebral and peripheral vasculature, with clinical
      manifestations including myocardial infarction, ischaemic stroke and peripheral
      arterial disease. Atherothrombosis represents a massive clinical and economic
      burden to healthcare, annually accounting for at least 22% of all deaths
      globally. Moreover, the prevalence of atherothrombotic disease is increasing as a
      result of increased longevity resulting in a larger cohort of older individuals.
      Stroke in particular is a major burden, and is the primary cause of adult
      disability, the second most important cause of dementia, and the third leading
      cause of death in industrialised countries. Atherothrombosis is also associated
      with a poor prognosis, significantly reducing life expectancy in the 60-year-old
      patient by 8-12 years depending on the vascular event. Moreover, this already
      shortened life expectancy is further and substantially reduced in patients with
      more than one atherothrombotic event. The economic burden of atherothrombosis is
      significant, particularly given its increasing prevalence, with the United States
      spending over US dollars 300 billion on it. There is thus a need for effective
      intervention to prevent or reduce mortality and morbidity. Evidence-based
      medicine using economics, clinical trials data, outcomes research, epidemiology
      and risk stratification are necessary to target treatment effectively to patients
      at greatest risk, in an attempt to reduce the burden of atherothrombotic disease.

PMID- 15876009
TI  - The value of clopidogrel versus aspirin in reducing atherothrombotic events: the
      CAPRIE study.
AB  - Atherothrombotic disease is a growing health problem, and is increasingly more
      costly to manage. Clopidogrel is an advanced, specific adenosine diphosphate
      receptor antagonist, which has been shown to be a highly potent antiplatelet
      agent. Data from the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic
      Events (CAPRIE) study have demonstrated the significantly superior clinical
      benefit of clopidogrel over aspirin for secondary prevention of atherothrombotic
      disease, with a relative risk reduction in myocardial infarction, stroke or
      vascular death of 8.7% (95% confidence interval 0.3, 16.5; P = 0.043). Moreover,
      clopidogrel demonstrated an amplified clinical benefit versus aspirin in patients
      at high risk of atherothrombotic events, such as those with a previous history of
      symptomatic atherothrombotic disease or with major risk factors such as diabetes
      mellitus or hypercholesterolaemia. On the basis of commonly accepted threshold
      criteria (Euros 20000 per life-year gained; LYG), clopidogrel in comparison with
      aspirin is cost-effective for the secondary prevention of atherothrombotic
      disease (cost per LYG ranging from Euros 19462 to Euros 3256). Economic analyses
      have demonstrated consistent cost-effectiveness results with clopidogrel in
      different countries. Moreover, in high-risk patient subgroups the cost
      effectiveness of clopidogrel in comparison with aspirin was evenbetter (cost per
      LYG ranging from Euros 5900 to Euros 6310). Compared with other treatment
      strategies used for the prevention of ischaemic or atherothrombotic events, the
      cost-effectiveness of clopidogrel in comparison with aspirin based on CAPRIE is
      favourable, with most analyses in the intermediate range of cost-effectiveness.
      The available data thus support the use of clopidogrel as a clinically efficient
      and cost-effective option for secondary prevention of atherothrombotic disease,
      particularly in high-risk patients.

PMID- 15876010
TI  - The value of clopidogrel in addition to standard therapy in reducing
      atherothrombotic events.
AB  - The recent multinational, randomised, prospective studies Clopidogrel in Unstable
      Angina to Prevent Recurrent Events (CURE), Percutaneous Coronary Intervention
      substudy of CURE (PCI-CURE) and Clopidogrel for the Reduction of Events During
      Observation (CREDO) have demonstrated the clinical efficacy and safety of
      clopidogrel for the treatment of patients with non-ST-segment elevation acute
      coronary syndromes (ACS), including those undergoing percutaneous coronary
      intervention. In these settings, clopidogrel significantly reduces the risk of
      atherothrombotic events, with relative risk reductions of 20-30% (absolute risk
      reduction 1.9-3.0%). Health economic evaluations based on data from these studies
      conducted in Europe and the United States have clearly demonstrated the cost
      effectiveness of clopidogrel in combination with aspirin compared with aspirin
      alone for the management of ACS. Within-trial evaluations based on CURE and PCI
      CURE data showed that treatment with clopidogrel on top of standard therapy
      reduced the cost of initial hospitalisation as well as the total cost associated
      with hospitalisations. Long-term economic analyses based on the CURE study
      demonstrate that clopidogrel is cost saving in the Netherlands and that the cost
      per life-year gained (LYG) in other European countries is between Euros 549 and
      Euros 5048. In the United States, the cost per LYG for clopidogrel has been
      assessed at US dollars 6173 on the basis of CURE, US dollars 5910 for PCI-CURE
      and US dollars 3685 for CREDO, all of which are considerably lower than that
      associated with common cardiovascular benchmarks. The results are robust and
      consistent across different countries using varying costing strategies and
      estimates of survival. In conclusion, these data demonstrate that clopidogrel in
      combination with aspirin for the management of ACS is both clinically effective
      and cost-effective in this setting.

PMID- 15876011
TI  - Facile syntheses of quater-, penta-, and sexipyrroles.
AB  - alpha,alpha-Linked oligopyrroles are attractive precursors for both expanded
      porphyrin and conducting polymer chemistry. We demonstrate facile methods for
      synthesizing quater-, penta-, and sexipyrroles from more readily available bi-
      and terpyrrole intermediates. These products demonstrate stability in their
      brightly colored oxidized forms, while reduction using borohydride reagents gives
      the corresponding all-pyrrole oligomers, which oxidize readily in air. The
      oxidized quater- and sexipyrroles were characterized by single-crystal X-ray
      diffraction analysis.

PMID- 15876012
TI  - Designed cocrystals based on the pyridine-iodoalkyne halogen bond.
AB  - Diiodobutadiyne (1) and diiodohexatriyne (2) form cocrystals with bispyridyl
      oxalamides and ureas, based on the halogen bond between the alkynyl iodine and
      pyridine nitrogen. In each cocrystal, the oxalamide or urea host forms one
      dimensional hydrogen-bonded networks, aligning the diiodopolyyne for potential
      topochemical polymerization with a repeat distance matching the host repeat.

PMID- 15876013
TI  - Large molecular motions are tolerated in crystals of diamine double salt of trans
      chlorocinnamic acids with trans-1,2-diaminocyclohexane.
AB  - Contrary to the general assumption that photoreactions in crystals may not
      proceed with large molecular motions, a pedal-like motion prompted by electronic
      excitation is believed to be involved during the beta-dimer formation from the
      crystals of the diamine double salt of trans-2,4-dichlorocinnamic acid and trans
      1,2-diaminocyclohexane.

PMID- 15876014
TI  - Organic dyes incorporating low-band-gap chromophores for dye-sensitized solar
      cells.
AB  - Versatile dyes based on benzothiadiazole and benzoselenadiazole chromophores have
      been developed that perform efficiently in dye-sensitized solar cells. Power
      conversion efficiency of 3.77% is realized for a dye in which charge
      recombination is probably hindered by the nonplanar charge-separated structure.

PMID- 15876015
TI  - A recyclable electrochemical allylation in water.
AB  - To develop environmentally benign processes for C-C bond formation,
      electrochemistry is applied in a tin-mediated allylation reaction in water. In
      this electrochemical process, the corresponding homoallylic alcohols are prepared
      in excellent yields, while both tin salt and water can be recycled and electrode
      materials are not consumed.

PMID- 15876016
TI  - Synthesis of cationic water-soluble light-harvesting dendrimers.
AB  - Four generations of phenylenefluorene (1F)- and phenylenebis(fluorene) (2F)
      terminated polyamidoamine (PAMAM) dendrimers were synthesized by coupling
      activated esters with commercially available PAMAM precursors. Treatment of Boc
      terminated pendant groups on the optically active units with 3 M HCl in dioxane
      yields cationic water-soluble dendrimers. Fluorescence resonance energy transfer
      (FRET) experiments with the cationic dendrimers as the donor and double stranded
      DNA containing a fluorescein label as the acceptor reveal cooperative optical
      behavior.

PMID- 15876017
TI  - Synthesis of novel polycyclic indolyldiamines.
AB  - A rapid and stereoselective access to novel polycyclic indolyldiamines is
      described. The key step involves simple chemoselective transformations of a
      common bicyclic aminal intermediate, easily available on a large scale from an
      enantiomerically pure cyano oxazolopiperidine precursor.

PMID- 15876018
TI  - Chemoselective syntheses of gamma-butyrolactams using vinyl sulfilimines and
      dichloroketene.
AB  - Reactions between vinyl sulfilimines and dichloroketene generated in situ from
      trichloroacetyl chloride in the presence of zinc-copper couple give mixtures of
      alpha-dichloro-gamma-butyrolactams and alpha-dichloro-gamma-butyrolactone imines.
      Fine-tuning of substituents within vinyl sulfilimines results in reactions with
      good chemoselectivity and yield for lactams.

PMID- 15876019
TI  - Samarium diiodide-catalyzed diastereoselective pinacol couplings.
AB  - A complex of samarium diiodide (SmI(2)) with tetraglyme catalyzes the
      intermolecular pinacol coupling of aromatic or aliphatic aldehydes at loadings of
      10 mol % in the presence of Me(2)SiCl(2) and Mg. Diastereoselectivity of up to
      95/5 (+/-/meso) has been achieved for aliphatic aldehydes and up to 19/81 (+/
      /meso) for aromatic aldehydes. De values of up to 99% have been achieved in
      intramolecular pinacol coupling reactions using the
      SmI(2)/tetraglyme/Mg/Me(2)SiCl(2) catalytic system.

PMID- 15876020
TI  - pi-Arene/metal binding: an issue not only of structure but also of reactivity.
AB  - A trimethyl-, triethyl-, or triisopropylsilyl group attached to the meta position
      of toluene retards the rate of permutational hydrogen/metal interconversion with
      butyllithium in the presence of potassium tert-butoxide by factors of 1.7, 3, and
      7, respectively. Although remote from the reaction center, the substituents
      sterically impede the coordination of potassium to the arene electron sextet. pi
      Arene/metal bonding may play a major role in modulating chemical and, by
      extension, biochemical reactivity.

PMID- 15876021
TI  - Enantioselective ring-opening reaction of meso-epoxides with ArSeH catalyzed by
      heterometallic Ti-Ga-Salen system.
AB  - The first example of enantioselective ring-opening reaction of meso-epoxides with
      aryl selenols to give optically active beta-arylseleno alcohol in up to 97% ee
      was realized, using a chiral Ti-Ga-Salen heterometallic catalyst. A strong
      synergistic effect of different Lewis acids in the system was exhibited in the
      catalytic process.

PMID- 15876022
TI  - Efficient synthesis of an imidazole-substituted delta-amino acid by the
      integration of chiral technologies.
AB  - Two methods to produce (2S)-5-amino-2-(1-n-propyl-1H-imidazol-4-ylmethyl)
      pentanoic acid were investigated. Diastereoisomeric salt resolution, using the
      quinidine salt, gave the desired intermediate in 98% ee and 33% yield. Asymmetric
      hydrogenation of various substrates gave high conversions, with up to 83% ee.
      Integration of these two approaches via asymmetric hydrogenation of a quinidine
      salt substrate followed by crystallization provided the desired intermediate in
      94% ee and 76% yield.

PMID- 15876023
TI  - Synthesis of anemoclemoside B, the first natural product with an open-chain
      cyclic acetal glycosidic linkage.
AB  - Anemoclemoside B (1), the first natural product containing a brand-new glycosidic
      linkage, the open-chain cyclic acetal linkage, was synthesized.

PMID- 15876024
TI  - Synthetic studies toward the construction of the cis-decalin portion of
      superstolides A and B. Application of a sequential double michael reaction and an
      anionic oxy-Cope rearrangement.
AB  - A highly convergent strategy for the asymmetric synthesis of the cis-decalin
      portion of the antitumor macrolide superstolide A was developed. The key
      reactions in our approach involve a sequential double Michael reaction and an
      anionic oxy-Cope rearrangement.

PMID- 15876025
TI  - Iron-catalyzed homo-coupling of simple and functionalized arylmagnesium reagents.
AB  - Iron-catalyzed homo-coupling of simple and functionalized arylmagnesium reagents
      is described. The reaction is highly chemoselective (CN, COOEt and NO(2) groups
      are tolerated). The procedure was used to perform intramolecular couplings. This
      cyclization reaction is the key step of the total synthesis of the N
      methylcrinasiadine.

PMID- 15876026
TI  - Synthesis of PPAR agonist via asymmetric hydrogenation of a cinnamic acid
      derivative and stereospecific displacement of (S)-2-chloropropionic acid.
AB  - The synthesis of the peroxime proliferator activated receptor (PPAR) alpha,gamma
      agonist (1) was accomplished with high enantio- and diastereoselectivity by
      employing an asymmetric hydrogenation strategy, of an alpha-alkoxy cinnamic acid
      derivative, to set the C-2 chiral center. A diastereospecific S(N)2 displacement
      under mild basic conditions established the C-10 stereochemistry without any
      detectable racemization of the two epimerizable chiral centers.

PMID- 15876027
TI  - Click to fit: versatile polyvalent display on a peptidomimetic scaffold.
AB  - We describe an efficient protocol to effect multisite conjugation reactions to
      oligomers on solid-phase support. Sequence-specific N-substituted glycine
      "oligopeptoids" were utilized as substrates for azide-alkyne cycloaddition
      reactions. Diverse groups, including nucleobases and fluorophores, were
      conjugated at up to six positions on peptoid side chains with yields ranging from
      88 to 96%. This strategy will be broadly applicable for generating polyvalent
      displays on peptides and other scaffolds, allowing precise control of spacing
      between the displayed groups.

PMID- 15876028
TI  - Polymer-bound oxathiaphospholane: a solid-phase reagent for regioselective
      monothiophosphorylation and monophosphorylation of unprotected nucleosides and
      carbohydrates.
AB  - Two polymers bound to N,N-diisopropylamino-1,3,2-oxathiaphospholane were reacted
      with unprotected carbohydrates and nucleosides in the presence of 1H-tetrazole,
      followed by oxidation with tert-butyl hydroperoxide or sulfurization with
      Beaucage's reagent. The 1,3,2-oxathiaphospholane ring-opening with 3
      hydroxypropionitrile, followed by treatment with DBU, afforded the corresponding
      monophosphate and monothiophosphate derivatives, respectively, through the
      elimination of polymer-bound ethylene episulfide. Reactions using this strategy
      offer the advantages of high regioselectivity, monosubstitution, and facile
      isolation and recovery of products.

PMID- 15876029
TI  - Intramolecular hydroamination of unactived olefins with Ti(NMe2)4 as a
      precatalyst.
AB  - Commercially available Ti(NMe(2))(4) has been used effectively as a precatalyst
      in a facile protocol for the intramolecular hydroamination of aminoalkenes to
      yield pyrrolidine and piperidine heterocyclic products with isolated yields up to
      92%. Geminally substituted substrates display the highest reactivity. This
      precatalyst is also effective for the hydroamination of activated internal
      alkenes, providing access to more complex heterocyclic target molecules.

PMID- 15876030
TI  - Bipyridinium ionic liquid-promoted cross-coupling reactions between
      perfluoroalkyl or pentafluorophenyl halides and aryl iodides.
AB  - A new room-temperature ionic liquid has been synthesized from 2,2'-bipyridine.
      This liquid improved the copper-catalyzed cross-coupling reactions between
      perfluoroalkyl or pentafluorophenyl halides and aryl iodides. Good recyclability
      using this solvent system was observed.

PMID- 15876031
TI  - Highly enantioselective conjugate addition of nitromethane to chalcones using
      bifunctional cinchona organocatalysts.
AB  - Cinchona alkaloid-derived chiral bifunctional thiourea organocatalysts were
      synthesized and applied in the Michael addition between nitromethane and
      chalcones with high ee and chemical yields.

PMID- 15876033
TI  - C1 C70F38 contains four planar aromatic hexagons; the parallel between
      fluorination of [60]- and [70]fullerenes.
AB  - The main C(1) isomer of C(70)F(38) is shown by single-crystal X-ray analysis to
      contain four planar aromatic hexagons and four isolated C=C bonds, has two
      fluorines on the equator, and is related to C(2) C(70)F(38) by means of three 1,3
      fluorine shifts. The C(1) and C(2) isomers thus parallel the T and C(3)/C(1)
      isomers of C(60)F(36) in containing three and four aromatic rings, respectively,
      and in the fluorine shift relationship.

PMID- 15876032
TI  - Molybdenum oxides as highly effective dehydrative cyclization catalysts for the
      synthesis of oxazolines and thiazolines.
AB  - In the presence of molybdenum oxide the dehydrative cyclization of N-acylserines,
      N-acylthreonines, and N-acylcysteines can be carried out under Dean-Stark
      conditions in toluene to give oxazolines and thiazolines. The ammonium salts
      (NH(4))(6)Mo(7)O(24).4H(2)O and (NH(4))(2)MoO(4) have excellent catalytic
      activities for the dehydrative cyclization of serine and threonine derivatives,
      and the acetylacetonate complex MoO(2)(acac)(2) has a remarkable catalytic
      activity for the dehydrative cyclization of cysteine derivatives. In addition,
      polyaniline-supported MoO(2)(acac)(2) can easily be recovered and reused.

PMID- 15876034
TI  - 4,5-Diazafluorene-incorporated ter(9,9-diarylfluorene): a novel molecular doping
      strategy for improving the electron injection property of a highly efficient OLED
      blue emitter.
AB  - A more efficient OLED device with blue emission characteristic of terfluorene has
      been achieved by using a novel molecular doping strategy, in which 4,5
      diazafluorene was incorporated as the substitution group of terfluorene to
      facilitate electron injection from the metal cathode yet without altering
      emission characteristics.

PMID- 15876035
TI  - Direct catalytic synthesis of enantiopure 5-substituted oxazolidinones from
      racemic terminal epoxides.
AB  - A venerable scaffold for asymmetric synthesis and drug development, chiral 5
      substituted oxazolidinones are obtained in almost enantiomerically pure form (up
      to 99.9% ee) starting from racemic terminal epoxides. The salient features of
      this process include the very simple and convenient experimental protocol and the
      employment of a readily accessible catalyst and inexpensive, easily handled
      starting materials. An enantioconvergent approach for the total conversion of
      racemic epoxide into a single stereoisomeric oxazolidinone is also described.

PMID- 15876036
TI  - A phosphine-catalyzed [3+6] annulation reaction of modified allylic compounds and
      tropone.
AB  - A novel phosphine-catalyzed reaction of modified allylic compounds, including
      acetates, bromides, chlorides, or tert-butyl carbonates derived from the Morita
      Baylis-Hillman (MBH) reaction with tropone to yield [3+6] annulation products in
      excellent yields was developed. It offers a simple and convenient method for
      constructing bridged nine-membered carbocycles.

PMID- 15876037
TI  - Electronic nature of N-heterocyclic carbene ligands: effect on the Suzuki
      reaction.
AB  - Suzuki reactions of aryl chlorides and arylboronic acids with a range of
      electronically different N-heterocyclic carbene ligands derived from N,N
      diadamantylbenzimidazolium salts are reported. Results indicate that an electron
      rich NHC ligand enhances the rate of oxidative addition. However, reductive
      elimination is unchanged by the electronic nature of the supporting ligand and is
      primarily affected by the steric environment.

PMID- 15876039
TI  - Selective synthesis of phosphate monoesters by dehydrative condensation of
      phosphoric acid and alcohols promoted by nucleophilic bases.
AB  - Phosphate monoesters are synthesized from a mixture of phosphoric acid (1 or 2
      equiv) and alcohols (1 equiv) in the presence of tributylamine. The reaction is
      promoted by nucleophilic bases such as N-alkylimidazole and 4-(N,N
      dialkylamino)pyridine. 2',3'-O-Isopropylidene ribonucleosides are selectively
      converted to their 5'-monophosphates without the protection of amino groups in
      nucleobases.

PMID- 15876038
TI  - Role of the A-ring of bryostatin analogues in PKC binding: synthesis and initial
      biological evaluation of new A-ring-modified bryologs.
AB  - The syntheses of three newly designed bryostatin analogues are reported. These
      simplified analogues, which lack the A-ring present in the natural product but
      possess differing groups at C9, were obtained using a divergent approach from a
      common intermediate. All three analogues exhibit potent, single-digit nanomolar
      affinity to protein kinase C.

PMID- 15876040
TI  - Phosphine-mediated coupling of gramines with aldehydes: a remarkably simple
      synthesis of 3-vinylindoles.
AB  - A new and practical synthesis of terminally substituted 3-vinylindoles is
      described involving tributylphosphine-mediated coupling of gramines with
      aldehydes.

PMID- 15876042
TI  - A modular approach to polyketide building blocks: cycloadditions of nitrile
      oxides and homoallylic alcohols.
AB  - A general approach to the diastereoselective synthesis of Delta(2)-isoxazolines
      via magnesium-mediated, hydroxyl-directed diastereoselective nitrile oxide
      cycloadditions of homoallylic alcohols and monoprotected homoallylic diols is
      disclosed. A broad spectrum of aliphatic and aromatic nitrile oxides and a
      variety of homoallylic alcohols participate in the cycloaddition, thus expanding
      the scope of polyketide building blocks that can be accessed using this strategy.

PMID- 15876041
TI  - Preparation of 1-thio uronic acid lactones and their use in oligosaccharide
      synthesis.
AB  - The chemo- and regioselective TEMPO/BAIB-mediated oxidation of 2,6- and 3,6
      dihydroxy 1-thio glycopyranosides to the corresponding 1-thio uronic acid
      lactones is described. These locked 1-thio glycuronides can directly be used as
      donors in glycosidation reactions using the Ph(2)SO/Tf(2)O reagent system.
      Alternatively, selective opening of the lactone bridge liberates a hydroxyl
      function for ensuing glycosylations.

PMID- 15876043
TI  - Synthesis of cis-fused carbo-bicycles by domino enyne cross
      metathesis/intramolecular Diels-Alder Reaction.
AB  - A sequential combination of Ru-catalyzed enyne cross-metathesis (EYCM) and
      intramolecular Diels-Alder reaction (IMDA) is described. Different terminal
      alkynes and alpha,omega-dienes obtained by a Baylis-Hillman reaction were
      transformed into substituted cis-hexahydro-1H-indenes and cis-hexahydro-2H
      naphthalin-1-ones.

PMID- 15876044
TI  - A desymmetrization route to fused Troger's base analogues: synthesis, isolation,
      and characterization of the first anti-anti diastereomer of a fused tris-Troger's
      base analogue.
AB  - A desymmetrization route to fused Troger's base analogues was developed. In this
      way, the synthesis of the first example of an anti-anti diastereomer of a fused
      tris-Troger's base analogue was accomplished. The resulting compound 5b is a
      nonlinear symmetric regioisomer obtained from p-bromoaniline in 7% yield. The
      corresponding syn-anti diastereomer 5a was obtained in 4% yield.

PMID- 15876045
TI  - Xenibellols A and B, new diterpenoids from the formosan soft coral Xenia
      umbellata.
AB  - Xenibellols A (1) and B (2), possessing an unprecedented diterpenoid skeleton,
      were isolated from the soft coral Xenia umbellata. The structures of xenibellols
      A and B were established by extensive analysis of spectroscopic data.

PMID- 15876046
TI  - Intramolecular hydrogen abstraction promoted by amidyl radicals. Evidence for
      electronic factors in the nucleophilic cyclization of ambident amides to
      oxocarbenium ions.
AB  - A tandem 1,5-hydrogen atom transfer/radical oxidation/nucleophilic cyclization
      mechanism is proposed for the intramolecular hydrogen abstraction reaction
      promoted for primary carboxamidyl radicals. The electron-withdrawing capacity of
      the C-5 substituent can switch the reaction to give exclusively bicyclic
      spirolactams (6-oxa-1-azaspiro[4.5]decan-2-one) when R(1) = H or spirolactones
      (1,6-dioxaspiro[4.5]decan-2-one) when R(1) = OAc. With a substituent of medium
      polarity (R(1) = OMe), a mixture of lactones and lactams is formed.

PMID- 15876047
TI  - Cascade iminium ion reactions for the facile synthesis of quinolizidines. Concise
      syntheses of (+/-)-epilupinine and (-)-epimyrtine.
AB  - Several novel cascade processes have been designed and developed that involve
      sequential reactions of imines and iminium ions to form substituted quinolizidine
      ring systems in a single step from simple and readily available starting
      materials. The utility and promise of these cascade reactions is evident from
      their application to extraordinarily concise syntheses of the representative
      quinolizidine alkaloids (+/-)-epilupinine and (-)-epimyrtine.

PMID- 15876048
TI  - Synthesis of lactams via copper-catalyzed intramolecular vinylation of amides.
AB  - Copper-catalyzed intramolecular vinylation of iodoenamides were investigated for
      the first time. With CuI as the catalyst and N,N'-dimethylethylenediamine as the
      ligand, a number of iodoenamides underwent cyclization in dioxane leading to the
      formations of five- to seven-membered lactams in moderate to excellent yields.

PMID- 15876049
TI  - Short asymmetric synthesis of (-)- and (+)-cis-lauthisan.
AB  - The asymmetric synthesis of both enantiomers of cis-lauthisan (3) is achieved in
      only six steps from diethyl pimelate (4), the key steps being the
      diastereodivergent reduction of beta-ketosulfoxide 7 and the highly cis
      stereoselective Et(3)SiH/TMSOTf-promoted reductive cyclization of enantiopure
      hydroxy sulfinyl ketones (S)-14 and (R)-14.

PMID- 15876050
TI  - Silicon-directed oxa-Pictet-Spengler cyclization and an unusual dimerization of 2
      trimethylsilanyl tryptophols.
AB  - The tetrahydro-pyrano[3,4-b]indoles 6 were synthesized from 2-(2-trimethylsilanyl
      1H-indol-3-yl)-ethanols 5 and various ketones or aldehydes through silicon
      directed oxa-Pictet-Spengler cyclizations. An unusual reaction led to the dimeric
      products 7 when some of 5 was treated with acetone using BF(3) as the catalyst.

PMID- 15876051
TI  - Synthesis of cyclopropanes via organoiron methodology: preparation and
      rearrangement of divinylcyclopropanes.
AB  - Addition of alkenyl Grignard reagents to (1-methoxycarbonylpentadienyl)iron(1+)
      cation generates the corresponding (2-alkenylpent-3-en-1,5-diyl)iron complexes.
      Oxidatively induced-reductive elimination of these complexes gives
      divinylcyclopropanes which can undergo subsequent Cope rearrangement to give 1,4
      cycloheptadienes.

PMID- 15876052
TI  - Reductive spiroannulation of nitriles with secondary electrophiles.
AB  - The scope of reductive decyanation and spiroannulation reactions has been
      expanded to include secondary electrophiles for potentially useful
      transformations. Secondary phosphates and chlorides, as well as terminal
      epoxides, cyclize in a stereospecific fashion. Both endo and exo modes of
      cyclization were observed with terminal epoxides.

PMID- 15876053
TI  - Homolytic fragmentation of allyloxychlorocarbene.
AB  - The decomposition of allyloxychlorocarbene in hydrocarbon solvents leads via
      homolysis to allyl and COCl radicals, which recombine to 3-butenoyl chloride or
      (after scission of (*)COCl to CO and (*)Cl) to allyl chloride. Labeling
      experiments show that both products are formed in part with allylic
      rearrangement.

PMID- 15876054
TI  - Acids direct 2-styrylcyclobutanone into two distinctly different reaction
      pathways.
AB  - Two structurally distinct carbocycles were selectively obtained by the reactions
      of 2-(o-styryl)cyclobutanones promoted by ytterbium salts. Treatment of the
      cyclobutanones with YbCl(3) in 1,4-dioxane at 100 degrees C afforded 2-(2
      chloroethyl)naphthalenes. On the other hand, the reaction with Yb(OTf)(3) in
      chlorobenzene at 130 degrees C gave 9,10-dihydrobenzocycloocten-7(8H)-ones.

PMID- 15876055
TI  - Efficient synthesis of alpha-galactosyl ceramide analogues using glycosyl iodide
      donors.
AB  - The combination of reactive galactosyl iodide donors with electron-rich acceptor
      lipids provides highly stereoselective and efficient routes to alpha GalCer
      analogues. Using per-O-silylated donors, key intermediates can be obtained in a
      three-step, one-pot sequence providing useful constructs for analogue
      development.

PMID- 15876056
TI  - Promoter-dependent course of the Beckmann rearrangement of stereoisomeric
      spiro[4.4]nonane-1,6-dione monoximes.
AB  - Activation of the Beckmann rearrangement of the enantiopure spirocyclic keto
      oximes (-)-9 and (-)-12 has been initiated with four acidic promoters. In two
      cases (PPE and PPSE), concerted 1,2 shift of the anti carbon operates
      exclusively. This is not the case with PPA or Eaton's reagent, although optical
      activity is fully maintained in these ring expansions as well.

PMID- 15876057
TI  - Rhodium-catalyzed addition of arylzinc reagents to aryl alkynyl ketones:
      synthesis of beta,beta-disubstituted indanones.
AB  - A rhodium-catalyzed addition of arylzinc reagents to aryl alkynyl ketones for the
      synthesis of highly substituted indanones has been developed. The key to success
      has proved to be a proper choice of the reaction system, which involves the
      employment of dppf as a ligand and 1,2-dichloroethane as a solvent.

PMID- 15876058
TI  - A new class of ammonium ylid for [2,3]-sigmatropic rearrangement reactions: ene
      endo-spiro ylids.
AB  - The first examples of sigmatropic rearrangements of ene-endo-spirocyclic,
      tetrahydropyridine-derived ammonium ylids are reported. Thus, spiro[6.7]-ylids
      rearrange primarily by a [2,3]-pathway, whereas the analogous [6.6]-ylids
      rearrange by [1,2]- and [2,3]-mechanisms in roughly equal proportions. This
      method serves as a rapid entry to the core of a range of alkaloids bearing a
      pyrrolo[1,2-a]azepine or octahydroindolizidine nucleus.

PMID- 15876060
TI  - Regio- and stereoselective route to tetrasubstituted olefins by the palladium
      catalyzed three-component coupling of aryl iodides, internal alkynes, and
      arylboronic acids.
AB  - [reaction: see text] The Pd-catalyzed three-component coupling of readily
      available aryl iodides, internal alkynes, and arylboronic acids provides a
      convenient, one-step, regio- and stereoselective route to tetrasubstituted
      olefins in good to excellent yields, although electron-poor aryl iodides and
      dialkylalkynes normally afford only low yields under our standard reaction
      conditions. The proper combination of substrates and reaction conditions is
      important for high yields. The presence of water generally substantially
      increases the yields of the desired tetrasubstituted olefins. The reaction
      involves cis-addition of the aryl group from the aryl iodide to the less hindered
      or more electron-rich end of the alkyne, while the aryl group from the
      arylboronic acid adds to the other end. A modified, room-temperature procedure
      has also been successfully developed, which works very well for some substrates.
      Tamoxifen and its derivatives are synthesized in a concise, regio- and
      stereoselective manner by applying our synthetic protocol.

PMID- 15876061
TI  - Determining the absolute stereochemistry of secondary/secondary diols by 1H NMR:
      basis and applications.
AB  - [structures: see text] The absolute configuration of 1,2-, 1,3-, 1,4-, and 1,5
      diols formed by two secondary (chiral) hydroxy groups can be deduced by
      comparison of the NMR spectra of the corresponding bis-(R)- and bis-(S)-MPA
      esters. The correlation between the NMR spectra of the bis-ester derivatives and
      the absolute stereochemistry of the diol involves the comparison of the chemical
      shifts of the signals for substituents R1/R2 and for the hydrogens attached to
      the two chiral centers [H(alpha)(R1) and H(alpha)(R2)] in the bis-(R)- and the
      bis-(S)-ester and is expressed as delta deltaRS. Theoretical calculations [energy
      minimization by semiempirical (AM1), ab initio (HF), DFT (B3LYP), and Onsager
      methods, and aromatic shielding effect calculations] and experimental data (NMR
      and CD spectroscopy) indicate that in these bis-MPA esters, the experimental
      delta deltaRS values are the result of the contribution of the
      shielding/deshielding effects produced by the two MPA units that combine
      according to the actual stereochemistry of the diol. The reliability of these
      correlations is demonstrated with a wide range of diols of known absolute
      configuration derivatized with MPA and 9-AMA as auxiliary reagents. A simple
      graphical model that allows the simultaneous assignment of the two asymmetric
      carbons of a 1,n-diol by comparison of the NMR spectra (delta deltaRS signs) of
      its bis-(R)- and bis-(S)-AMAA ester derivatives is presented.

PMID- 15876062
TI  - Efficient unimolecular deprotonation of aniline radical cations.
AB  - [reaction: see text] Deprotonation of the radical cations of aromatic amines,
      such as anilines, generally occurs much more slowly than other fragmentation
      reactions. Here we report a stereoelectronic effect involving twisting of the
      anilino group out of the plane of the benzene ring that results in a
      significantly increased rate of reactivity toward deprotonation. Quantitative
      studies of the rate constants for deprotonation as a function of aniline radical
      cation pKa (Bronsted plots) demonstrate that the effect is not simply due to a
      change in the reaction thermodynamics. By combining this stereoelectronic effect
      with covalent attachment of carboxylate as a base, aniline radical cations that
      undergo unimolecular deprotonation with rate constants as high as 10(8) s(-1),
      even in unfavorable protic media, are described.

PMID- 15876063
TI  - Unexpected formation of polysubstituted 1-azabutadienes and 1,3-dioxanes from the
      reaction of 3-fluoroalkyl-3-arylaminoacrylic acid esters with formaldehyde.
AB  - [reaction: see text] The reaction of 3-fluoroalkyl-3-arylaminoacrylic acid esters
      with formaldehyde was described. In the presence of a catalytic amount of
      triethylamine, the reaction took place readily in acetonitrile at 70 degrees C to
      give the corresponding 2-fluoroalkyl-1-azabutadienes in good yields. cis
      Fluoroalkylated 1,3-dioxanes were obtained predominantly when the aryl ring
      contained an electron-withdrawing group and the reaction was carried out at room
      temperature under catalysis of triethylamine and tetrabutylammonium bromide. A
      possible mechanism was proposed.

PMID- 15876064
TI  - An evolved explanation for the molecular geometry and electronic structure of
      diphenyl-substituted cyclic trimethylenemethane in the ground state: a nearly
      planar conformation with a considerably localized electronic state.
AB  - [structures: see text] We reinvestigated the molecular geometry and electronic
      structure of the diphenyl-substituted, five-membered cyclic trimethylenemethane
      (TMM) diradical (Berson's TMM, 3**) using UV/VIS absorption and emission
      spectroscopy combined with density functional theory (DFT) and time-dependent
      (TD)-DFT calculations. Two intense absorption bands, A and B, with lambda(ab) at
      298 and 328 nm, respectively, a weak absorption band C, with lambda(ab) at 472
      nm, and an intense emission band D, with lambda(em) at 491 nm, were observed for
      3**. By comparing the spectrum of 3** with those of the 1,1-diphenylethyl (7*)
      and cyclopent-2-en-1-yl (9*) radicals, it was found that bands B, C, and D
      originated from the diphenylmethyl radical moiety (subunit I), while band A
      should most likely be assigned to an electronic transition related to an
      interaction between subunit I and residual subunit II, the cyclopentenyl radical
      moiety. An UB3LYP/cc-pVDZ calculation indicated that, in the ground state, the
      two unpaired electrons of 3** are mainly localized in subunits I and II,
      respectively, and the interaction between them is inefficient, despite the nearly
      planar conformation (theta = +23.5 degrees). Furthermore, a TD-UB3LYP/cc-pVDZ
      calculation suggested that absorption band A is assigned to an electronic
      transition involved with enhancement of the electron density of the C-2-C-3 bond.
      Substituent effects on the absorption and emission spectra of 3** using 11** and
      13** support the conclusion based on the experiments and calculations. Therefore,
      we propose an evolved explanation for the molecular geometry and electronic
      structure of the ground state of 3** in a low-temperature matrix, a nearly planar
      conformation with a considerably localized electronic state, which alone accounts
      for the spectroscopic characteristics.

PMID- 15876065
TI  - Oxidative cyclorelease from soluble polymeric supports.
AB  - [reaction: see text] Single electron oxidation is shown to be a viable method for
      effecting concomitant cyclization and cleavage (cyclorelease) of a series of
      polymer bound homobenzylic ethers. Soluble oligonorbornene polymers are stable
      toward redox chemistry and are isolable through precipitation with methanol,
      making them excellent supports for this process. These oxidative conditions are
      also shown to cleave secondary and tertiary alcohols and ethers in a new
      traceless approach to polymer-supported aldehyde and ketone synthesis.

PMID- 15876066
TI  - Convenient synthesis of epsilon-halo-beta-ketoesters and gamma,gamma'
      dibromoalkanones by regio- and chemoselective reaction of 2
      alkylidenetetrahydrofurans with boron trihalides: a "ring-closure/ring-cleavage"
      strategy.
AB  - [reaction: see text] The reaction of boron tribromide and boron trichloride with
      2-alkylidenetetrahydrofurans, readily available on the basis of cyclizations of
      free and masked dianions with 1,2-dielectrophiles, allowed an efficient synthesis
      of a variety of carbonyl compounds with remote halide functionality. This
      includes the chemo- and regioselective synthesis of 6-bromo- and 6-chloro-3
      oxoalkanoates and 1,7-dibromoheptan-4-ones. The approach outlined herein can be
      regarded as a "ring-closure/ring-cleavage" strategy.

PMID- 15876067
TI  - Synthesis of 3'-deoxy-3'-difluoromethyl azanucleosides from trans-4-hydroxy-l
      proline.
AB  - [reaction: see text] Two strategies were tried to synthesize 3'-deoxy-3'
      difluoromethyl azanucleosides. After the failure of the first route, the key
      intermediate 12 from trans-4-hydroxyproline 7 in 8 steps was stereoselectively
      prepared. The alcohol 12 was subjected to selective protection, oxidation, and
      difluoromethylenation to afford the fluorinated compound 18, whose hydrogenation
      was then systematically investigated. After a series of transformations of
      protecting groups, the resultant compounds 22 and 23 were oxidized to the desired
      lactams 24 and 25, which were successfully utilized to synthesize our target
      molecules, 3'-deoxy-3'-difluoromethyl azanucleosides 33, 34a, 34b, and 35.

PMID- 15876068
TI  - Systematic study of the synthesis of macrocyclic dipeptide beta-turn mimics
      possessing 8-, 9-, and 10- membered rings by ring-closing metathesis.
AB  - [structures: see text] A systematic study was performed to establish general
      synthesis protocols for forming enantiomerically pure macrocyclic dipeptide
      lactams. Focusing on macrocycles of 8-, 9-, and 10-membered rings, effective
      syntheses were achieved by a sequence featuring peptide coupling of allyl- and
      homoallyl-glycine building blocks followed by ring-closing metathesis. The 8
      membered lactam-possessing cis-amide and cis-olefin geometry as well as 9
      membered [corrected] lactams having trans-amide and cis-olefin [corrected]
      configurations were effectively prepared by a general strategy employing the
      respective protected dipeptide, the first generation Grubbs' catalyst, and
      temporary protection of the central amide as a benzyl derivative. The 10-membered
      macrocycle was synthesized possessing cis- or trans-olefin geometry by employing
      similar metathesis conditions in the presence or absence of temporary benzyl
      amide protection, respectively [corrected]

PMID- 15876069
TI  - Cyclic nitriles: diastereoselective alkylations.
AB  - [reaction: see text] Diastereoselective alkylations of metalated conformationally
      locked 4-tert-butylcyclohexanecarbonitrile are highly diastereoselective with
      magnesium and copper counterions but only modestly diastereoselective with
      lithium as the counterion. Selective generation of diverse metalated nitriles is
      readily achieved through bromine-magnesium, -copper, and -lithium exchange
      reactions of the corresponding bromonitrile or, for lithium, by deprotonating the
      parent nitrile with lithium diethylamide. Collectively, high alkylation
      stereoselectivities correlate with the retentive alkylations of C-metalated
      nitriles, whereas N-lithiated nitriles alkylate with modest selectivity,
      reflecting minimal steric differences in the corresponding axial and equatorial
      electrophile trajectories.

PMID- 15876070
TI  - Photoreactions of 1-acetylisatin with alkynes: regioselectivity in oxetene
      formation and easy access to 3-alkylideneoxindoles and
      dispiro[oxindole[3,2']furan[3',3' ']oxindole]s.
AB  - [reaction: see text] Photoinduced reactions of 1-acetylisatin (IS) with
      diphenylacetylenes 1a-c, 1-(p-methoxyphenyl)propyne 2, and 1,4-diphenyl-1,3
      butadiyne 3 gave beta,beta-disubstituted 3-alkylidene oxindoles 6-12 respectively
      via [2+2] cycloaddition of 3IS* with the alkyne and subsequent oxetene ring
      opening. Photoreactions of IS with phenylacetylenes 4a-d and cyclopropylacetylene
      5 furnished the dispiroindole[3,2']furan[3',3' ']indoles 13 and 14. Compounds 13
      and 14 are formed in tandem reactions initiated by [2+2] cycloaddition of 3IS*
      with the alkynes to give spirooxetenes Va and Vb, which upon spontaneous ring
      opening gave the alpha,beta-unsaturated aldehydes IVa and IVb. It is proposed
      that hydrogen abstraction of 3IS* from the C(O)-H functionality in IV followed by
      dissociation of the triplet isatin ketyl (A)-aldehyde acyl (B) radical pair and
      an oxygenphilic attack of the acyl radical B at the C3 carbonyl oxygen atom of a
      neutral IS gave the 2:1 (IS:4) radical C, which took part in an intramolecular
      radical cyclization to give the dispiroindole[3,2']furan[3',3' ']indoles 13 and
      14. The regioselectivity in the [2+2] photocycloadditions of IS with 4 to afford
      the oxetene Va depends on the intervening of the more stable 1,4-diradical
      intermediates VI, which have a linear alpha-phenyl-substituted vinyl radical
      where the phenyl provides spin delocalization of the radical center at the sp
      carbon atom.

PMID- 15876071
TI  - Manganese(III)-mediated oxidative annulation of methylenecyclopropanes with 1,3
      dicarbonyl compounds.
AB  - [reactions: see text] Manganese(III)-mediated oxidative annulation of
      methylenecyclopropanes with 1,3-dicarbonyl compounds in acetic acid produces 4,5
      dihydrofuran derivatives as [3+2] annulation products in moderate to good yields
      under mild conditions. The possible reaction mechanism is discussed on the basis
      of previous mechanistic investigation.

PMID- 15876072
TI  - Microwave-assisted multistep synthesis of functionalized 4-arylquinolin-2(1H)
      ones using palladium-catalyzed cross-coupling chemistry.
AB  - [reaction: see text] Biologically active 4-aryl-3-alkenyl-substituted quinolin
      2(1H)-ones have been synthesized in a short and concise manner employing readily
      available 4-hydroxyquinolin-2(1H)-ones as intermediates. Key steps in the
      synthesis include the derivatization of the quinolin-2(1H)-one cores using
      palladium-catalyzed Suzuki and Heck reactions, installing the 4-aryl and 3
      alkenyl substituents. All synthetic transformations (six steps) required for the
      synthesis of the desired target quinolin-2(1H)-one were carried out using
      controlled microwave-assisted organic synthesis.

PMID- 15876073
TI  - Preparation of multisubstituted allenes from allylsilanes.
AB  - [reaction: see text] A three-step route of converting allylsilanes to
      functionalized allenes was developed. Thermal decomposition of 1,1-dibromo-2
      (silylmethyl)cyclopropanes, which were quantitatively prepared by treatment of
      allylsilane derivatives with CHBr3/KO(t)Bu, afforded substituted 2-bromo-1,3
      butadienes with elimination of bromosilanes. The Pd-catalyzed reaction of the
      bromodienes with soft nucleophiles gave the allene derivatives. Previously
      inaccessible tri- and tetrasubstituted allenes can be prepared by this method as
      well.

PMID- 15876074
TI  - Adducts of thianthrene- and phenoxathiin cation radical salts with symmetrical
      alkynes. Structure and formation of cumulenes on alumina leading to alpha
      diketones, alpha-hydroxyalkynes, and alpha-acetamidoalkynes.
AB  - [reaction: see text] Thianthrene cation radical tetrafluoroborate (Th*+ BF4-)
      added to 2-butyne, 3-hexyne, 4-octyne, and 5-decyne in MeCN to form trans
      bisadducts R(Th+)C=C(Th+)R, where R = Me, Et, Pr, Bu (7a-d). Phenoxathiin cation
      radical tetrafluoroborate (PO*+ BF4-) added similarly to the last three alkynes
      to form adducts R(PO+)C=C(PO+)R, 8b-d. Cyclic monoadducts were not found. The
      trans structures of 7 and 8 were deduced with X-ray crystallography (7c) and NMR
      spectroscopy. When solutions of adducts in CHCl3 and MeCN were deposited on
      activated alumina, elimination of thianthrene (Th) and phenoxathiin (PO) occurred
      almost quantitatively. Detailed studies with (7b-d) indicated that a cumulene
      (15) was formed by the elimination of Th and that 15 was subsequently converted
      into small amounts of other products. In CHCl3, these products were the
      respective alkyne, thianthrene 5-oxide, an alpha-diketone (11), an alpha
      hydroxyalkyne (12), and hydrogen. The same products were formed in MeCN along
      with an alpha-acetamidoalkyne (13). The formation of 15 and products derived from
      it is explained and was confirmed by preparation and reactions of 2,3,4
      hexatriene.

PMID- 15876075
TI  - The effect of ring substitution on the O-neophyl rearrangement of 1,1
      diarylalkoxyl radicals. A product and time-resolved kinetic study.
AB  - [reaction: see text] A product and time-resolved kinetic study of the effect of
      ring substitution on the reactivity of 1,1-diarylalkoxyl radicals has been
      carried out. The radicals undergo an O-neophyl shift to give the isomeric 1-aryl
      1-aryloxyalkyl radicals from which the corresponding aromatic ketones are formed.
      The rearrangement rate constants are influenced by ring substitution, increasing
      in the presence of electron-withdrawing substituents and decreasing in the
      presence of electron-donating ones. From the results of product and kinetic
      studies, the following migratory aptitudes have been obtained: 4
      trifluoromethylphenyl > phenyl approximately = 4-methylphenyl > 4-methoxyphenyl.
      Excellent Hammett-type correlations between the sigma+ substituent constants and
      both the visible absorption band maxima and the rearrangement rate constants have
      been obtained. The experimental results indicate that the rearrangement is
      governed by electronic effects in the starting 1,1-diarylalkoxyl radicals,
      whereas the stability of the rearranged carbon-centered radical plays a minor
      role, in line with a reactant-like transition state, strongly supporting the
      hypothesis that the O-neophyl rearrangement of 1,1-diarylalkoxyl radicals
      proceeds through a concerted mechanism.

PMID- 15876076
TI  - N-methylation of peptides on selected positions during the elongation of the
      peptide chain in solution phase.
AB  - [reactions: see text] An efficient and general solution-phase method for the site
      specific N-methylation of peptides has been developed. This novel procedure
      involves synthesis of N-nosyl protected peptides and their subsequent N
      methylation with diazomethane. Its efficiency was proved by the successful
      synthesis of various hindered oligopeptides containing N-methyl amino acid
      residues with excellent yield and purity. The method is particularly attractive
      in that the adopted conditions do not cause any detectable racemization of the
      peptide stereocenters and the process does not require chromatographic
      purification of the methylated products. A further advantage is the compatibility
      of this methodology with Fmoc solution-phase peptide synthesis.

PMID- 15876077
TI  - An N-acyliminium cyclization approach to a total synthesis of (+)-cylindricine C.
AB  - [reaction: see text] Details of problems and solutions encountered during the
      development of an enantioselective total synthesis of (+)-cylindricine C are
      described here. The total synthesis itself was accomplished in 8 steps, featuring
      an N-acyliminium cyclization strategy, the seldom-used Wharton rearrangement, and
      a key epimerization at C5.

PMID- 15876078
TI  - Determination of molecular structure using vibrational circular dichroism
      spectroscopy: the keto-lactone product of Baeyer-Villiger oxidation of (+)
      (1R,5S)-bicyclo[3.3.1]nonane-2,7-dione.
AB  - [reaction: see text] The Baeyer-Villiger oxidation of (+)-(1R,5S)
      bicyclo[3.3.1]nonane-2,7-dione, 1, can lead to four keto-lactone products, 2a-d.
      A single isomer is obtained experimentally. We have used IR and VCD
      spectroscopies to identify the structure of this product. DFT calculations of the
      IR and VCD spectra of 2a-d show unambiguously that the experimental product is
      (+)-(1R,6R)-2a, and not the expected product 2b. NMR studies, including
      comparison of DFT and experimental 1H and 13C spectra, support this conclusion.
      This work provides the first example of the use of VCD spectroscopy to
      discriminate between structural isomers of a chiral molecule. The specific
      rotation of (+)-(1R,6R)-2a, predicted using TDDFT methods, is negative
      demonstrating that absolute configurations determined from TDDFT calculations of
      specific rotations are not 100% reliable.

PMID- 15876079
TI  - Synthesis of optically pure 1,2-diaryl- and 1,2-alkylaryl-1,2-amino sulfides.
AB  - [reaction: see text] The reactions of the lithium (S)-alpha-(methylthio)-2-(p
      toluenesulfinyl)benzyl carbanion with (S)-N-p-tolylsulfinyl aldimines evolve in a
      completely stereoselective manner providing a one-step synthesis of
      enantiomerically pure anti-1,2-disubstituted 1,2-amino sulfide derivatives.

PMID- 15876080
TI  - Are electrocyclization reactions of (3Z)-1,3,5-hexatrienone and nitrogen
      derivatives pseudopericyclic? A DFT study.
AB  - [reactions: see text] Electrocyclization reactions of (3Z)-1,3,5-hexatrienone and
      nitrogen derivatives were studied by performing density functional theory (DFT)
      calculations together with the 6-31+G* basis set. Reactants, products, and
      transition states for each reaction were localized and the IRC connecting
      reactants and products was also obtained. Magnetic properties were evaluated
      along the reaction path to elucidate the characteristics of the reactions
      studied. As obtained from the calculations, electrocyclization of (3Z)-1,3,5
      hexatrienone is a pericyclic process, as indicated by a variety of indexes, such
      as Nucleus Independent Chemical Shift (NICS), anisotropy of the magnetic
      susceptibility, or anisotropy of the current-induced density (ACID). This
      reaction presents characteristics of pericyclic reactions despite the activation
      energy lowering relative to the electrocyclization of (4Z)-1,2,4,6-heptatetraene,
      and the relatively small NICS values observed in the transition state. Magnetic
      properties indicate that an enhancement of the aromaticity relative to reactants
      and products occurs revealing the absence of orbital disconnections on the cyclic
      loop of interacting orbitals. Only two reactions among those studied exhibit
      pseudopericyclic character due to the in-plane attack of the lone pair on
      nitrogen. In these cases, the reactions showed no barrier for the
      electrocyclization process, and no aromaticity enhancement was observed.

PMID- 15876081
TI  - Anthryl-substituted heterocycles as acid-sensitive fluorescence probes.
AB  - [reaction: see text] Four pH-sensitive fluorescence probes are presented which
      consist of an anthracene fluorophore and a pi-conjugated oxazoline, benzoxazole,
      or pyridine substituent. The protonation of the heterocycles increases their
      acceptor properties and results in significant red-shifts of the absorption and
      emission maxima of the anthracene chromophore. The comparison between 2-[2'-(6'
      methoxyanthryl)]-4,4-dimethyl-2-oxazoline and 2-[2'-(anthryl)]-4,4-dimethyl-2
      oxazoline reveals that the donor-acceptor substitution pattern of the fluorophore
      is not required to achieve a red shift upon protonation. The benzoxazole and
      pyridine substituents offer a particular advantage due to their persistence under
      acidic conditions. Thus, these compounds may be used as efficient pH-sensitive
      fluorescence switches. Nevertheless, the switching of benzoxazole 2c requires
      relatively strong acidic conditions. The anthrylpyridinium exhibits a red-shifted
      emission in chloroform; however, it is nonfluorescent in aqueous or alcoholic
      solution. Although the oxazoline is not persistent under permanent acidic
      conditions, this heterocycle may be useful as a substituent in fluorescence
      indicators since it may be used to detect acid concentrations of 10(-4)-10(-5) M,
      which are close to the biologically relevant range.

PMID- 15876082
TI  - Synthesis and properties of hexakis(6-octyl-2-azulenyl)benzene as a multielectron
      redox system with liquid crystalline behavior.
AB  - [structure: see text] This paper describes the cyclotrimerization reaction of
      di(2-azulenyl)acetylenes (2a,b) catalyzed by Co2(CO)8 to produce hexa(2
      azulenyl)benzene derivatives (1a,b). The cyclooligomerization of 2a and 2b
      utilizing CpCo(CO)2 as a catalyst produced (eta5-cyclopentadienyl)[tetra(2
      azulenyl)cyclobutadiene]cobalt complexes (3a,b). The redox behavior of hexakis(6
      octyl-2-azulenyl)benzene (1b), bis(6-octyl-2-azulenyl)acetylene (2b), and the
      cobalt complexes 3a and 3b along with 6-octyl-2-phenylazulene (19) was examined
      by cyclic voltammetry (CV). The reduction of compound 1b exhibited multiple
      electron transfers in one step upon CV with a reduction potential similar to that
      of compound 19. However, the CVs of compounds 2b, 3a, and 3b were characterized
      by stepwise waves because of the reduction of each azulene ring. The mesomorphic
      behaviors of 1b, 2b, and 19 were also studied by differential scanning
      calorimetry (DSC), polarizing optical microscopy (POM), and X-ray diffraction
      (XRD) techniques. A new series of azulene derivatives, 1b, 2b, and 19,
      substituted by a long alkyl chain at the 6-position shows mesomorphism with
      crystalline polymorphs. Compound 1b showed a large temperature range of hexagonal
      columnar mesophases (Col(ho)) from 115.5 to 199.9 degrees C. Compound 2b has
      rectangular columnar (Col(ro)), smectic E (S(E)), and nematic (N) mesophases.
      Compound 19 exhibited an S(E) mesophase.

PMID- 15876083
TI  - Stereoselective Suzuki-Miyaura cross-coupling reactions of potassium
      alkenyltrifluoroborates with alkenyl bromides.
AB  - [reaction: see text] The stereoselective synthesis of conjugated dienes using air
      stable potassium alkenyltrifluoroborates as coupling partners is described. The
      palladium-catalyzed cross-coupling reaction of potassium (E)- and (Z)
      alkenyltrifluoroborates with either (E)- or (Z)-alkenyl bromides proceeds readily
      with moderate to excellent yields to give the corresponding (E,E)-, (E,Z)-, (Z,E)
      , or (Z,Z)-conjugated dienes stereospecifically. The cross-coupling can generally
      be effected using 5 mol % of Pd(OAc)2, 10 mol % of PPh3, and 3 equiv of Cs2CO3 in
      THF-H2O (10:1). A variety of functional groups are tolerated in both coupling
      partners.

PMID- 15876084
TI  - Convenient synthesis of substituted piperidinones from alpha,beta-unsaturated
      amides: formal synthesis of deplancheine, tacamonine, and paroxetine.
AB  - [reaction: see text] An intermolecular aza-double Michael reaction leading to
      functionalized piperidin-2-ones from simple starting materials has been
      developed. The method allows alpha,beta-unsaturated amides to be used as a
      synthon of the piperidine nucleus. In addition, the utility of this methodology
      is demonstrated by its application to a formal synthesis of the indolo[2,3
      a]quinolizidine alkaloids, (+/-)-deplancheine, (+/-)-tacamonine, and the
      antidepressant paroxetine.

PMID- 15876085
TI  - A general strategy for the synthesis of vincamajine-related indole alkaloids:
      stereocontrolled total synthesis of (+)-dehydrovoachalotine, (-)-vincamajinine,
      and (-)-11-methoxy-17-epivincamajine as well as the related quebrachidine diol,
      vincamajine diol, and vincarinol.
AB  - [structures: see text] The highly convergent stereocontrolled total synthesis of
      (-)-vincamajinine (7), (-)-11-methoxy-17-epivincamajine (9), and the oxygen
      bridged (+)-dehydrovoachalotine (22) are described. Key steps in the synthesis of
      7 and 9 involved the stereospecific enolate-driven palladium-catalyzed cross
      coupling reaction, a Tollens reaction, an acid-assisted intramolecular
      cyclization to form the C(7)-C(17) quaternary center, and two stereospecific
      reductions. The efficiency of this strategy is illustrated by the completion of
      the synthesis of 7 and 9 in 16 [from d-(+)-tryptophan methyl ester 17] and 17
      (from the Schollkopf chiral auxiliary 27) reaction vessels, respectively. This
      constitutes the first total synthesis of these indole alkaloids and provides the
      first regiospecific route to 11-methoxy-substituted ajmaline/vincamajine-related
      alkaloids. The synthesis of 22 required a novel DDQ-mediated cyclization to
      furnish the C(6)-O(17) bond, executed in stereospecific fashion. Completion of
      these syntheses illustrates a concise and versatile strategy for the synthesis of
      vincamajine-related alkaloids, which has also been employed to prepare the
      related compounds quebrachidine diol (53), vincamajine diol (56), and vincarinol
      (59).

PMID- 15876086
TI  - A new interpretation of the Baylis-Hillman mechanism.
AB  - [reaction: see text] On the basis of reaction rate data, we have proposed a new
      mechanism for the Baylis-Hillman reaction involving the formation of a hemiacetal
      intermediate. We have determined that the rate-determining step is second order
      in aldehyde and first order in DABCO and acrylate. We have shown that this
      mechanism is general to aryl aldehydes under polar, nonpolar, and protic
      conditions using both rate data and two isotope effect experiments.

PMID- 15876087
TI  - Alpha-N-acetylmannosamine (ManNAc) synthesis via rhodium(II)-catalyzed oxidative
      cyclization of glucal 3-carbamates.
AB  - [reaction: see text] Glucal 3-carbamates 1 and 7 underwent oxidative cyclization
      with iodobenzene diacetate or iodosobenzene in the presence of Rh2(OAc)4,
      providing mannosamine 2-N,3-O-oxazolidinones. With iodosobenzene, incorporation
      of 4-penten-1-ol provided a readily separable anomeric mixture of n-pentenyl
      glycosides, with the anomers exhibiting pronounced differences in reactivity as
      glycosyl donors. N-acylation of the sugar oxazolidinones led to alpha-selective
      glycosyl donors for the elaboration of various 2-mannosamine frameworks.
      Alternatively, the anomeric n-pentenyl glycosides of N-Cbz 2-mannosamine
      oxazolidinones were converted separately to oxazolidinone-opened derivatives
      28alpha and 28beta. These served as stereoconvergent glycosyl donors, and the
      alpha-linked products were readily advanced to a variety of N-acetylmannosamine
      (ManNAc) frameworks, using an intramolecular O-->N acetyl transfer as the final
      step.

PMID- 15876088
TI  - Regioselective synthesis of 1,5-diaryl-1H-imidazoles by palladium-catalyzed
      direct arylation of 1-aryl-1H-imidazoles.
AB  - [reaction: see text] A variety of 1,5-diaryl-1H-imidazoles have been
      regioselectively synthesized by direct coupling of 1-aryl-1H-imidazoles with aryl
      iodides or bromides in DMF in the presence of CsF as the base and a catalyst
      precursor consisting of a mixture of Pd(OAc)2 and AsPh3. The data obtained in
      this synthetic study support a reaction mechanism involving an electrophilic
      attack of an arylpalladium(II) halide species onto the imidazole ring.
      Interestingly, some imidazole derivatives synthesized in this study have been
      found to exhibit significant cytotoxic activity against human tumor cell lines.

PMID- 15876089
TI  - A controllable synthesis of homoallyl ketones and multiply substituted
      cyclopentadienes by direct insertion of aroyl cyanides to zirconacyclopentenes.
AB  - [reaction: see text] The direct reaction of aroyl cyanides with
      zirconacyclopentenes was achieved cleanly under controlled reaction conditions.
      This methodology provided an extremely efficient, one-pot, and high-yield route
      for the synthesis of homoallyl ketones when the reaction was carried out at -50
      degrees C. Trapping of the zirconium intermediate by a variety of electrophiles
      afforded functionalized homoallyl ketones. Remarkably, the insertion reaction
      occurred with complete chemoselectivity, that means, the Zr-sp3 carbon bond
      reacted preferentially, which is different from Cu-mediated elaboration of
      zirconacycles. Surprisingly, when the reaction was done at room temperature,
      1,2,3-trisubstituted cyclopentadiene derivatives were readily formed in high
      yields. The direct insertion reaction of zirconacyclopentanes with acyl cyanides
      was also described. When bicyclic zirconacyclopentanes were used, cyclopentanol
      derivatives were obtained with high stereoselectivity.

PMID- 15876090
TI  - Isolation, X-ray structures, and electronic spectra of reactive intermediates in
      Friedel-Crafts acylations.
AB  - [reaction: see text] Reactive intermediates in the Friedel-Crafts acylation of
      aromatic donors are scrutinized upon their successful isolation and X-ray
      crystallography at very low temperatures. Detailed analyses of the X-ray
      parameters for the [1:1] complexes of different aliphatic and aromatic-acid
      chlorides with the Lewis acids antimony pentafluoride and pentachloride, gallium
      trichloride, titanium and zirconium tetrachlorides provide unexpected insight
      into the activation mechanism for the formation of the critical acylium
      carbocations. Likewise, the X-ray-structure examinations of aliphatic and
      aromatic acylium electrophiles also isolated as crystalline salts point to the
      origins of their electrophilic reactivity. Although the Wheland intermediates (as
      acylium adducts to arene donors) could not be isolated in crystalline form owing
      to their exceedingly short lifetimes, transient (UV-vis) spectra of benzenium
      adducts of acylium carbocations with hexamethylbenzene can be measured and
      directly related to Wheland intermediates with other cationic electrophiles that
      have been structurally established via X-ray studies.

PMID- 15876091
TI  - A theoretical investigation of alpha-carbon kinetic isotope effects and their
      relationship to the transition-state structure of S(N)2 reactions.
AB  - [reaction: see text] The transition structures and alpha-carbon 12C/13C kinetic
      isotope effects for 22 S(N)2 reactions between methyl chloride and a wide variety
      of nucleophiles have been calculated using the B1LYP/aug-cc-pVDZ level of theory.
      Anionic, neutral, and radical anion nucleophiles were used to give a wide range
      of S(N)2 transition states so the relationship between the magnitude of the alpha
      carbon kinetic isotope effect and transition-state structure could be determined.
      The results suggest that the alpha-carbon 12C/13C kinetic isotope effects for
      S(N)2 reactions will be large (near the experimental maximum) and that the curve
      relating the magnitude of the KIE to the percent transfer of the alpha-carbon
      from the nucleophile to the leaving group in the transition state has a broad
      maximum. This means very similar KIEs will be found for early, symmetric, and
      late transition states and that one cannot use the magnitude of these KIEs to
      estimate transition-state structure.

PMID- 15876092
TI  - Biocatalytic racemization of aliphatic, arylaliphatic, and aromatic alpha
      hydroxycarboxylic acids.
AB  - [reaction: see text] Biocatalytic racemization of a range of aliphatic,
      (aryl)aliphatic, and aromatic alpha-hydroxycarboxylic acids was accomplished by
      using whole resting cells of a range of Lactobacillus spp. The mild
      (physiological) reaction conditions ensured an essentially "clean" isomerization
      in the absence of side reactions, such as elimination or decomposition. Whereas
      straight-chain aliphatic 2-hydroxycarboxylic acids were racemized with excellent
      rates (up to 85% relative to lactate), steric hindrance was observed for branched
      chain analogues. Good rates were observed for aryl-alkyl derivatives, such as 3
      phenyllactic acid (up to 59%) and 4-phenyl-2-hydroxybutanoic acid (up to 47%). In
      addition, also mandelate and its o-chloro analogue were accepted at a fair rate
      (45%). This biocatalytic racemization represents an important tool for the
      deracemization of a number of pharmaceutically important building blocks.

PMID- 15876093
TI  - Solvent-free reaction of some 1,2-diaza-1,3-butadienes with phosphites:
      environmentally friendly access to new diazaphospholes and E
      hydrazonophosphonates.
AB  - [structures: see text] The present article describes the reaction between 1,2
      diaza-1,3-butadienes and trialkyl phosphites, under an atmosphere of nitrogen and
      under solvent-free conditions, to give alkyl 3,3-dialkoxy-2H-1,2,3lambda5
      diazaphosphole-4-carboxylates that, in turn, are converted into corresponding E
      hydrazonophosphonates by treatment with THF:water (95:5). These latter compounds
      are obtained directly by the reaction of 1,2-diaza-1,3-butadienes with trialkyl
      phosphites in the presence of air. These compounds are useful for the further
      preparation of dialkyl (5-methyl-3-oxo-2,3-dihydro-1H-4-pyrazolyl)phosphonates
      and 2-dialkoxyphosphoryl-1,2,3-thiadiazoles.

PMID- 15876094
TI  - Syntheses of 2,5-disubstituted dihydrofurans from gamma-substituted chiral
      allenamides.
AB  - [reaction: see text] Details of a synthesis of dihydrofurans using gamma
      substituted chiral allenamides are described here. Some transformations of these
      dihydrofurans are also examined including a highly stereoselective
      dihydroxylation and a rare account of a Lewis acid-mediated removal of an N-acyl
      substituent at the anomeric carbon of a tetrahydrofuran ring system. These
      studies provide further support for the synthetic utility of allenamides.

PMID- 15876095
TI  - Controlled synthesis of cis or trans isomers of 1,3-disubstituted
      tetrahydroisoquinolines and 2,5-disubstituted pyrrolidines.
AB  - [reactions: see text] The stereoselective outcome of Pd(II)- or Ag(I)-catalyzed
      intramolecular N-alkylation to afford 1,3-disubstituted 1,2,3,4
      tetrahydroisoquinolines was examined. In the absence of additional substituents,
      Pd(II) allows a facile access to the cis isomers, while Ag(I) favors formation of
      the trans isomers. The same observation was made for the synthesis of 2,5
      disubstituted pyrrolidines. Possible reasons for the observed stereoselectivities
      are discussed.

PMID- 15876096
TI  - meso-Alkyl-substituted meso-meso linked diporphyrins and meso-alkyl-substituted
      meso-meso, beta-beta, beta-beta triply linked diporphyrins.
AB  - [reaction: see text] AgPF6-promoted oxidation of 5,10,15-trialkyl zinc(II)
      porphyrins led to formation of meso-meso linked diporphyrins, which were further
      oxidized with Sc(OTf)3 and DDQ to give meso-meso, beta-beta, beta-beta triply
      linked diporphyrins that exhibited a stronger aggregation propensity than
      corresponding meso-aryl diporphyrins.

PMID- 15876097
TI  - Palladium(II)-catalyzed enyne coupling reaction initiated by acetoxypalladation
      of alkynes and quenched by protonolysis of the carbon-palladium bond.
AB  - [reaction: see text] Divalent palladium-catalyzed inter- and intramolecular enyne
      coupling reactions initiated by acetoxypalladation of alkynes were developed. The
      reaction involves the acetoxypalladation of the alkyne, followed by the insertion
      of the alkene and the protonolysis of the carbon-palladium bond. The protonolysis
      of the carbon-palladium bond in the presence of bidentate nitrogen containing
      ligands is the key step in completing the Pd(II) catalytic cycle. The nitrogen
      containing ligands, like halides, served to favor the protonolysis of the carbon
      palladium bond over the beta-H elimination in the Pd(II)-mediated reactions. The
      intermolecular coupling reactions provide an efficient method for synthesizing
      gamma,delta-unsaturated carbonyls. The intramolecular coupling reactions offer a
      method to construct a variety of synthetically important carbo- and heterocycles.
      The asymmetric version of such a cyclization was developed with moderate
      enantioselectivity when employing pymox (pyridyl monooxazoline) as the ligand.

PMID- 15876098
TI  - NiCl2-catalyzed hydrophosphinylation.
AB  - [reaction: see text] A new nickel-based catalytic system has been developed for
      phosphorus-carbon bond formation. The addition of alkyl phosphinates to alkynes
      is catalyzed by nickel chloride in the absence of added ligand. The reaction
      generally proceeds in high yields, even with internal alkynes, which were poor
      substrates in our previously reported palladium-catalyzed hydrophosphinylation of
      alkyl phosphinates. The method is useful for the preparation of H-phosphinate
      esters and their derivatives. The one-pot synthesis of various important
      organophosphorus compounds is also demonstrated. The reaction can be conducted
      with microwave heating.

PMID- 15876099
TI  - Formation of stable Meisenheimer adduct ion pairs in apolar solvents:
      implications for stereoselective reactions.
AB  - [reaction: see text] A detailed study concerning the formation of Meisenheimer
      adducts in biphasic solvent systems is described. The process relies on utilizing
      a significantly lipophilic quaternary ammonium salt to transfer a nucleophile
      (e.g., hydroxide ion) between an aqueous and organic layer containing the
      electron-deficient aromatic substrate. Provided that the organic layer is
      sufficiently apolar, the resultant Meisenheimer adduct is considerably stable,
      likely the result of a strong ion-pairing interaction between the large
      polarizable anionic complex and the diffusively charged tetraalkylammonium
      cation. Using the diethylamide of 3,5-dinitrobenzoic acid as a model compound,
      the influence of ion-pairing reagents and solvents on adduct formation was
      investigated. Dramatically increased equilibrium formation of the Meisenheimer
      adduct is observed in the biphasic medium (e.g., benzene/2 M NaOH) relative to
      the same adduct generated in single-phase systems. Spectroscopic studies on this
      adduct are consistent with those conducted in single-phase polar or dipolar
      aprotic solvents. The methodology is extended to performing highly
      enantioselective biphasic kinetic resolutions of several racemic electron
      deficient amides.

PMID- 15876100
TI  - Stereodivergent syntheses of anisomycin derivatives from D-tyrosine.
AB  - [structures: see text] Enantiomerically pure 2-alkyl-3-acetoxy-4-iodopyrrolidines
      with all groups cis, and all adjacent groups trans (10 and 17), important
      precursors for the synthesis of pyrrolidinediols, have been prepared from D
      tyrosine through regio- and diastereoselective reduction of a vinyl ketone and
      subsequent iodoamidation controlled by minimization of nonbonding steric
      interactions. Highly stereodivergent Woodward-Prevost methodology, applied to
      both iodopyrrolidines, yielded enantiomerically pure (2R,3R,4R)-, (2R,3R,4S)-,
      and (2R,3S,4R)-deacetylanisomycin (3, 4, and 5), each in excellent de.
      Incorporation of differential protection of the hydroxyl groups led to a one-pot
      synthesis of (2R,3R,4R)-anisomycin 2.

PMID- 15876101
TI  - Intramolecular cyclization of delta-iminoacetylenes: a new entry to pyrazino[1,2
      a]indoles.
AB  - [reaction: see text] The synthesis of the pyrazino[1,2-a]indole nucleus was
      achieved by intramolecular cyclization of several 2-carbonyl-1-propargylindoles
      in the presence of ammonia. The reaction conditions were optimized using
      microwave heating and a pool of catalysts. Cyclization of 1-alkynylindole-2
      carbaldehydes was easily accomplished under standard heating conditions, whereas
      microwave heating contributed to reduced reaction times and improved overall
      yields. Moreover, a fine-tuning of the microwave irradiation time made possible
      the selective synthesis of both pyrazino[1,2-a]indole isomers. TiCl4 proved the
      catalytic system of choice to achieve pyrazinoindoles in satisfactory yields
      starting from 1-alkynyl-2-acetylindoles and 1-alkynyl-2-benzoylindole
      derivatives. Also in these cases, microwave heating contributed to faster
      reactions and improved yields. The uncatalyzed versus catalyzed reaction
      mechanism is discussed.

PMID- 15876102
TI  - Synthesis and structural analysis of the anilides of glucuronic acid and
      orientation of the groups on the carbohydrate scaffolding.
AB  - [structures: see text] The synthesis of anilides derived from glucuronic acid is
      described. Secondary anilides had a Z configuration in the solid state and showed
      intramolecular and intermolecular hydrogen bonding. However, on the basis of NMR
      and IR studies, there was generally no evidence for the same hydrogen bonding in
      solution. Tertiary anilides showed a strong preference for the E configuration on
      the basis of NOE studies and molecular mechanics calculations. The alkylation of
      the secondary anilides induces a configurational switch that alters the
      orientation of the aromatic group with respect to the pyranose, which has
      relevance for presentation or orientation of pharmacophoric groups on
      carbohydrate scaffolds.

PMID- 15876103
TI  - Synthesis of structurally defined scaffolds for bivalent ligand display based on
      glucuronic acid anilides. The degree of tertiary amide isomerism and folding
      depends on the configuration of a glycosyl azide.
AB  - [structures: see text] Syntheses and structural analyses of bivalent
      carbohydrates based on anilides of glucuronic acid are described. Secondary
      anilides predominantly adopted the Z-anti structure; there is also evidence for
      population of the Z-syn isomer. Bivalent tertiary anilides displayed two signal
      sets in their NMR spectra, consistent with the presence of (i) a major isomer
      where both amides have E configurations (EE) and (ii) a minor isomer where one
      amide is E and the other Z (EZ). Qualitative NOE/ROE spectroscopic studies in
      solution support the proposal that the anti conformation is preferred for E
      amides. The crystal structure of one bivalent tertiary anilide showed E-anti and
      E-syn structural isomers; intramolecular carbohydrate-carbohydrate stacking was
      observed and mediated by carbonyl-pyranose, azide-azide, and pyranose-aromatic
      interactions. The EE to EZ isomer ratio, or the degree of folding, for tertiary
      amides, was greatest for a bivalent compound containing two alpha-glycosyl azide
      groups; this was enhanced in water, suggesting that hydrophobic interactions are
      partially but not wholly responsible. Computational methods predicted azide
      aromatic (N...H-C interaction) and azide-azide interactions for folded isomers.
      The close contact of the azide and aromatic protons (N...H-C interaction) was
      observed upon examination of the close packing in the crystal structure of a
      related monomer. It is proposed that the alpha-azide group is more optimally
      aligned, compared to the beta-azide, to facilitate interaction and minimize the
      surface area of the hydrophobic groups exposed to water, and this leads to the
      increased folding. The alkylation of bivalent secondary anilides induces a switch
      from Z to E amide that alters the scaffold orientation. The synthesis of a
      bivalent mannoside, based on a secondary anilide scaffold, for investigation of
      mannose-binding receptor cross-linking and lattice formation is described.

PMID- 15876104
TI  - Novel deoxygenation reaction of epoxides by indium.
AB  - [reaction: see text] A novel, mild, ecofriendly protocol for the deoxygenation of
      epoxides to alkenes using indium metal and indium(I) chloride or ammonium
      chloride in alcohol has been developed. It was necessary for the presence of good
      radical-stabilizing groups adjacent to the oxirane ring for the deoxygenation
      reaction to occur. It is proposed that this reaction occurs through an SET
      process with indium as an electron donor.

PMID- 15876105
TI  - Functionalized azabicycloalkane amino acids by nitrone 1,3-dipolar intramolecular
      cycloaddition.
AB  - [reaction: see text] An efficient and operationally simple method for the
      synthesis of functionalized azaoxobicyclo[X.3.0]alkane amino acids has been
      devised. The key step is an intramolecular nitrone cycloaddition on 5-allyl- or 5
      homoallylproline that was found to be completely regio- and stereoselective.

PMID- 15876106
TI  - Crucial role of elusive isomeric eta-complexes in gas-phase electrophilic
      aromatic alkylations.
AB  - [isomers: see text] The kinetics and stereochemistry of the protonation-induced
      unimolecular isomerization of (R)-1-D1-3-(p-fluorophenyl)butane have been
      investigated in the gas phase at 40-100 degrees C and 70-760 Torr. This process
      leads to the formation of the relevant meta and ortho isomers with partial
      racemization of the migrating sec-butyl moiety. Complete racemization is
      observed, instead, when the isomerization reaction involves a 1,2-H shift in the
      moving alkyl group. These results, together with the relevant activation
      parameters, fully confirm the previous evidence of the occurrence in the alkyl
      cation/arene PES of noncovalent eta-type intermediates of defined structure and
      stability, lying well below the classical pi-complexes, as confirmed by ab initio
      calculations. Their crucial role in determining the positional selectivity of gas
      phase electrophilic aromatic substitutions clearly emerges from the comparison of
      the present results with the site selectivity measured in the corresponding
      bimolecular arene alkylation carried out at the same temperatures and pressures.

PMID- 15876107
TI  - Ketone-imide versus ketone-oxime reductive cross-coupling promoted by samarium
      diiodide: new mechanistic insight gained from a failed aminocyclopentitol
      synthesis.
AB  - [reaction: see text] The intramolecular 1,6-ketone/imide reductive coupling
      promoted by samarium diiodide competes favorably with an alternative 1,5
      ketone/oxime ether coupling in a keto-oxime substrate derived from D-glucosamine
      N-protected with a phthalimido group. This pinacol coupling reaction affords new
      homochiral alpha-hydroxylactam scaffolds that could be useful in diversity
      oriented synthesis. A mechanistic proposal for this reaction that explains the
      experimental results is supported by DFT quantum-mechanical calculations on model
      compounds.

PMID- 15876108
TI  - BODIPY-based hydroxyaryl derivatives as fluorescent pH probes.
AB  - [structures: see text] Seven new 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
      (BODIPY) dyes with phenolic or naphtholic subunits on position 8 and with
      substituents having different electron driving forces on positions 3 and 5 were
      synthesized. Their absorption and steady-state fluorescence properties were
      investigated as a function of solvent. The novel compounds, with the exception of
      4,4-difluoro-8-(4-hydroxyphenyl)-3,5-bis-(4-methoxyphenyl)-4-bora-3a,4a-diaza-s
      indacene, are characterized by absorption maxima in the range 493-515 nm and
      small (400-600 cm(-1)) Stokes shifts. The exceptional dye has absorption maxima
      in the 570-580 nm region and fluorescence emission maxima around 610-620 nm,
      depending on the solvent. In aqueous solution, the dyes show a large fluorescent
      enhancement upon increasing the acidity of the solution. They can be used in
      aqueous solution as fluorescent pH probes excitable with visible light, with pKa
      values ranging from 7.5 to 9.3, depending on the substitution pattern on
      positions 3, 5, and 8.

PMID- 15876109
TI  - Enantioselective synthetic method for alpha-alkylserine via phase-transfer
      catalytic alkylation of 2-phenyl-2-oxazoline-4- carbonylcamphorsultam.
AB  - [reaction: see text] An enantioselective synthetic method for alpha-alkylserines
      by the phase-transfer catalytic alkylation of 2-phenyl-2-oxazoline-4
      carbonylcamphorsultam (4a) was developed. The phase-transfer catalytic alpha
      alkylation of 4a using P2-Et at -78 degrees C gave alpha-alkylation (75 to
      approximately 99%, 90 to approximately 97% de), which could be easily hydrolyzed
      to alpha-alkylserines.

PMID- 15876110
TI  - Addition of Cl2C: to (-)-O-menthyl acrylate under sonication-phase-transfer
      catalysis. Efficient synthesis of (+)- and (-)-(2-chlorocyclopropyl)methanol.
AB  - [reaction: see text] Dichlorocyclopropanation of (-)-O-menthyl acrylate under
      conditions of phase-transfer catalysis (CHCl3, KOH, tetramethylammonium bromide),
      with sonication, gives excellent yields (85-94%) of the corresponding
      dichlorocyclopropanecarboxylate ester compared to thermal conditions (90 degrees
      C, 56%). No diastereoselectivity was observed, but one isomer was isolated pure
      by fractional crystallization. The measured kinetic isotope effect (initial rate
      (CHCl3)/rate (CDCl3) approximately 1.7) suggests deprotonation of CHCl3 as the
      rate-limiting step.

PMID- 15876111
TI  - Design of sulfides with a locked conformation as promoters of catalytic and
      asymmetric sulfonium ylide epoxidation.
AB  - [reaction: see text] A new generation of 2,5-dimethylthiolanes with a locked
      conformation was developed to promote the asymmetric addition of chiral sulfonium
      ylides to aldehydes. The novel chiral sulfur derivative 4 succeeded the synthesis
      of trans-stilbene oxide derivatives with enantiomeric ratios ranging from 95:5 to
      98:2. This user-friendly organocatalytic process proved to be efficient with 20
      10% of sulfide 4 in 1 or 2 days of reaction. An insight into the ylide
      intermediate conformation is given on the basis of a computational ab initio
      study.

PMID- 15876112
TI  - Cyclopropylcarbinyl --> homoallyl-type ring opening of ketyl radical anions.
      Structure/reactivity relationships and the contribution of solvent/counterion
      reorganization to the intrinsic barrier.
AB  - [reaction: see text] Following a protocol developed by Mathivanan, Johnston, and
      Wayner (J. Phys. Chem. 1995, 99, 8190-8195), the radical anions of several
      cyclopropyl- and oxiranyl-containing carbonyl compounds were generated in an
      effort to measure the rate constants for their ring opening (k(o)) by laser flash
      photolysis. The results of these experiments are compared to those obtained from
      earlier electrochemical studies, and the combined data set is used to rationalize
      the kinetics of radical anion ring opening in a general context by using
      Saveant's theory pertaining to stepwise dissociative electron transfer (Acc.
      Chem. Res. 1993, 26, 455-461). Compared to cyclopropylcarbinyl --> homoallyl
      rearrangements of neutral free radicals, at comparable driving force, the radical
      anion ring openings are slightly slower. The small difference in rate is
      attributed to the contribution of an additional, approximately 2 kcal/mol,
      solvent reorganization component for the radical anion rearrangements. The
      solvent reorganization energy for ring opening of these radical anions is
      believed to be small because the negative charge does not move appreciably in the
      progression reactant --> transition state --> product.

PMID- 15876113
TI  - Reactivity of methyl mandelate-Ti(IV)-enediolate: oxidative homocoupling versus
      aldol and direct Mannich-type syn-diastereoselective condensation.
AB  - [reaction: see text] Methyl mandelate undergoes quantitative oxidative
      homocoupling on treatment with TiCl4/amine at room temperature. In the presence
      of ArCHO, quantitative syn-diastereoselective aldol condensation takes over the
      dimerization, whereas exclusive Mannich-type syn-diastereoselective reaction is
      observed in the presence of both ArCHO and PhNH2. The subsequent reactions of the
      title intermediate do not depend on how it is generated.

PMID- 15876114
TI  - Syntheses of stable N-tert-alkoxyarylaminyl mono- and diradicals by the reaction
      of the lithium salts of 2,4,6-trisubstituted anilines with tert-alkyl mono- and
      diperoxybenzoates.
AB  - [reaction: see text] The reaction of the lithium salts of 2,4,6-triaryl- and 2
      tert-butyl-4,6-diarylanilines with tert-alkyl mono- and diperoxybenzoates gave
      isolable N-tert-alkoxyarylaminyl mono- and diradicals. The substituent effects of
      tert-alkyl peroxybenzoates on the yields of N-tert-alkylarylaminyls were studied.

PMID- 15876115
TI  - Practical and efficient multigram preparation of a camphor-derived diol for the
      enantioselective Lewis acid catalyzed allylboration of aldehydes.
AB  - [reaction: see text] Chiral diols are important molecules with widespread use as
      chiral auxiliaries and ligands in enantioselective synthesis. Therefore,
      efficient and practical syntheses of highly dissymmetrical nonracemic diols are
      still a meaningful pursuit. Two new routes to access camphor-derived chiral diol
      1 have been developed. One route employs camphorquinone (3) as the starting
      material, affording in only two steps the desired diol in 55% overall yield. The
      second route, from camphor (2), leads to the desired diol in an efficient four
      step synthesis, with an overall yield of 55%.

PMID- 15876116
TI  - Synthesis of (+)-6beta-isovaleryloxylabda- 8,13-diene-7alpha,15-diol, a
      metabolite from Trismusculus reticulatus.
AB  - [structures: see text] A seven-step synthesis of (+)-6beta-isovaleryloxylabda
      8,13-diene-7alpha,15-diol has been achieved starting from (+)-larixol; this
      allowed determination of the absolute configuration of the metabolite isolated
      from the mucus of Trimusculus reticulatus.

PMID- 15876117
TI  - Palladium-catalyzed coupling of pyrazole triflates with arylboronic acids.
AB  - [reaction: see text] A general protocol for the palladium-mediated Suzuki
      coupling reaction of pyrazole triflates and aryl boronic acids has been
      developed. The use of additional dppf ligand was determined to increase product
      yields allowing for the use of a broad range of reaction substrates.

PMID- 15876118
TI  - 1,2-Thio group migration in Rh(II) carbene reactions.
AB  - [reaction: see text] A series of beta-thio group substituted alpha-diazo carbonyl
      compounds have been prepared by nucleophilic substitution reactions of
      thiophenol, thionaphthol, or benzyl mercaptan with beta-acetoxy-alpha-diazo
      carbonyl compounds. The diazo decomposition of these diazo carbonyl compounds
      with various transition metal catalysts, including Rh(II) carboxylates and Cu(I)
      and Cu(II) complexes, has been investigated. It was found that the diazo
      decomposition of these compounds gave 1,2-thio group migration products. No 1,2
      hydride or 1,2-aryl migration products were observed in all cases.

PMID- 15876119
TI  - Factors affecting stereocontrol during glycosidation of 2,3-oxazolidinone
      protected 1-tolylthio-N-acetyl-D-glucosamine.
AB  - [reaction: see text] It is demonstrated that a ring-fused 2,3-oxazolidinone
      protected derivative of 1-tolylthio-N-acetyl-D-glucosamine undergoes high-yield
      glycosidation under mild donor activation conditions. Stereoselective formation
      of alpha-linked or beta-linked glycosides is dependent on reactivity of acceptor
      alcohols, where rate of glycosidation correlates to stereochemical outcome.
      Evidence for the role of glycosyl triflate intermediates and the N-acetyl
      substituent of the 2N,3O-oxazolidinone ring in stereochemical control is
      presented.

PMID- 15876120
TI  - Convenient route to both enantiomers of a highly functionalized trans
      disubstituted cyclopentene. Synthesis of the carbocyclic core of the nucleoside
      BCA.
AB  - [structures: see text] Synthesis of both enantiomers of a highly functionalized
      cyclopentenol derivative, versatile building block for a vast array of
      biologically active compounds, is described. The key steps involve
      stereocontrolled synthesis of a diene with two syn-disposed substituents from a
      (R)-(+)-glyceraldehyde derivative, ring-closing metathesis of this diene, and
      functional group manipulation of the resulting trans-disubstituted cyclopentene.
      One of the enantiomers of the cyclopentenol thus obtained has been converted to
      an amino cyclopentene, the carbocyclic core of the nucleoside (-)-BCA, a potent
      inhibitor of HIV reverse transcriptase.

PMID- 15876121
TI  - An unprecedented concerted pathway in the alkaline hydrolysis of S-aryl
      thioesters.
AB  - [reaction: see text] Kinetic data indicate that the hydrolysis of S-2,4
      dinitrophenyl 4'-hydroxythiobenzoate in mild alkaline solutions (pH 8-11) most
      likely follows a dissociative, E1cB pathway, through a p-oxoketene intermediate,
      whereas at higher pH values an associative mechanism carries the reaction flux.
      Free linear energy relationships obtained from a kinetic study on the alkaline
      hydrolyses of substituted S-aryl 4'-hydroxythiobenzoates seem to suggest that the
      associative pathway is a concerted, one-step process, rather than the classical
      mechanism via a tetrahedral intermediate.

PMID- 15876122
TI  - Total synthesis of microcarpalide.
AB  - [reaction: see text] An efficient, convergent approach for the total synthesis of
      microcarpalide (1) is described. The synthetic strategy features the Sharpless
      asymmetric dihydroxylation, regioselective epoxide opening with various
      nucleophiles such as a lithium acetylide and cuprates derived from the vinyl
      stannane and the vinyl iodide for the construction of a C7-C8 trans-double bond
      and Yamaguchi macrolactonization as the key steps.

PMID- 15876123
TI  - One-pot Friedel-Crafts/Robinson-Gabriel synthesis of oxazoles using oxazolone
      templates.
AB  - [reaction: see text] We report herein a one-pot synthesis of 2,4,5-trisubstituted
      oxazoles via a Friedel-Crafts/Robinson-Gabriel synthesis using a general
      oxazolone template. Treatment of the oxazolone template with a range of aromatic
      nucleophiles provided the highly substituted oxazoles in good yields.

PMID- 15876124
TI  - Stereoselective addition of the titanium enolate of N-acetyl (4S)-isopropyl-1,3
      thiazolidine-2-thione to five-membered N-acyl iminium ions.
AB  - [reaction: see text] Addition of the chlorotitanium enolate of N-acetyl 4
      isopropyl-1,3-thiazolidine-2-thione to five-membered, N-substituted N-acyl
      iminium ions furnished the corresponding Mannich-type addition products with good
      diastereoselectivity and in good yields. The synthetic utility of the addition
      product 8 was demonstrated in a chemospecific anti-aldol reaction with
      cinnamaldehyde. By using this strategy, we constructed three contiguous chiral
      centers with high stereocontrol employing the same chiral auxiliary. X-Ray
      crystallographic analysis of addition product 2 and aldol product 14 revealed
      their absolute stereochemistry.

PMID- 15876128
TI  - Ultraviolet-B radiation upregulates expression of dectin-2 on epidermal
      Langerhans cells by activating the gene promoter.
AB  - Epidermal Langerhans cells (LC) belong to the antigen-presenting cell (APC)
      family of dendritic cells that can initiate antigen-specific immunogenic or
      tolerogenic responses. In mice, we have shown ultraviolet-B (UV-B) irradiation to
      induce long-lasting suppression (tolerance) of contact hypersensitivity responses
      by converting LC from immunogenic to tolerogenic APC. The C-type lectin receptor,
      dectin-2, expressed preferentially by LC and dendritic cells, has also been shown
      to be involved in inducing this form of UV-B-induced immunosuppression. These
      observations led us to question whether UV-B can modulate dectin-2 expression by
      LC. In ICR mice engineered to express the dectin-2 gene promoter linked to a
      luciferase reporter gene, we found broadband UV-B treatment in vivo to activate
      the promoter in LC. In wild-type C3H/HeN mice, we found such treatment in vivo to
      yield LC with increased dectin-2 expression at both mRNA and protein levels.
      Broadband UV-B treatment in vitro of bone marrow-derived dendritic cells from
      these mice also showed upregulated expression of dectin-2 mRNA. These findings
      lead us to conclude that broadband UV-B upregulates dectin-2 expression in LC by
      activating the dectin-2 gene promoter. Such amplification suggests that UV-B
      induced immunosuppression may be due (at least in part) to augmented dectin-2
      expression in LC.

PMID- 15876129
TI  - An improved outdoor calibration procedure for broadband ultraviolet radiometers.
AB  - This article aims at improving the broadband ultraviolet radiometer's calibration
      methodology. For this goal, three broadband radiometers are calibrated against a
      spectrophotometer of reference. Three different one-step calibration models are
      tested: ratio, first order and second order. The latter is proposed in order to
      adequately reproduce the high dependence on the solar zenith angle shown by the
      other two models and, therefore, to improve the calibration performance at high
      solar elevations. The proposed new second-order model requires no additional
      information and, thus, keeps the operational character of the one-step
      methodology. The models are compared in terms of their root mean square error and
      the most qualified is subsequently validated by comparing its predictions with
      the spectrophotometer measurements within an independent validation data subset.
      Results show that the best calibration is achieved by the second-order model,
      with a mean bias error and mean absolute bias error lower than 2.2 and 6.7%,
      respectively.

PMID- 15876130
TI  - Novel water-soluble photosensitizer based on starch and containing porphyrin.
AB  - Novel water-soluble polymeric photosensitizers (SPO) based on starch and
      containing porphyrin chromophores were synthesized and studied. The polymers were
      soluble in water and in dimethyl sulfoxide. Photophysical studies and
      solubilization of molecular probes proved the formation of hydrophobic, rigid
      microdomains in an aqueous solution of SPO; they were created due to the
      clustering of porphyrin chromophores attached to the polymer chain. SPO polymers
      absorbed light from the UV-visible spectral region. The polymers could sensitize
      photochemical reactions mediated by electron transfer, energy transfer or both,
      from the singlet-excited state of porphyrin chromophores to the molecules of
      organic compounds solubilized in the hydrophobic microdomains or residing in the
      water phase.

PMID- 15876131
TI  - Photophysical properties of methyl triazone included in MCM-41.
AB  - Methyl triazone (4,4',4''-[1,3,5-triazine-2,4,6-triyltriimino]tris-trimethyl
      benzoate) has been included in mesoporous MCM-41 (Mobil's composition of matter
      41) silica, and its fluorescence emission has been compared in solution and in
      the solid state. Although inclusion does not affect significantly the absorption
      properties, a fluorescence emission shift and a behavior similar to the solid
      state has been observed by increasing the loading. It is believed that this
      observation reflects molecular aggregation inside the MCM-41 channels. The
      potential of formulations of this type for sunscreen applications is discussed.

PMID- 15876133
TI  - Effect of ring methylation on the photophysical, photochemical and
      photobiological properties of cis-dichlorobis(1,10
      phenanthroline)rhodium(III)Chloride.
AB  - Methylated analogues of cis-dichlorobis(1,10-phenanthroline)rhodium(III)chloride
      (BISPHEN) have been prepared in order to increase the hydrophobicity of the
      parent compound, and thus create octahedral rhodium (III) complexes suitable for
      use as anticancer and antiviral agents that can be photoactivated. The parent
      complex has been shown in earlier work to be unable to cross through cell
      membranes. Octamethylation, as in the case of cis-dichlorobis(3,4,7,8-tetramethyl
      1,10-phenanthroline)rhodium(III)chloride (OCTBP), provides enough hydrophobicity
      to be taken up by KB tumor cells. It also provides a higher level of ground-state
      association with double-stranded DNA and increases the quantum efficiency of
      photoaquation by greater than 10-fold, relative to BISPHEN. OCTBP forms covalent
      bonds to deoxyguanosine when irradiated with the nucleoside, as has been seen
      with the parent complex. Irradiation of OCTBP in the presence of the KB or M109
      tumor cell lines using narrow-band UVB (lambda = 311 nm) irradiation initiates a
      considerable amount of phototoxicity. There is evidence that OCTBP acts as a
      prodrug (i.e. after passing through the cell membrane the metal complex is
      photolyzed to cis-chloro aquo OCTBP, which may be the active phototoxic agent).
      OCTBP and the tetramethyl analogue cis-dichlorobis(4,7-dimethyl-1,10
      phenanthroline)rhodium(III)chloride (47TMBP) also show photoaquation upon
      excitation with visible light (lambda > 500 nm), and indeed, some phototoxicity
      of KB cells is observed at these wavelengths as well. This is attributed to
      direct population of photoactive triplet-excited states. These results, together
      with our earlier studies of cis-dichloro[dipyrido(3,2-a: 2',3'-c)phenazine (1,10
      phenanthroline)rhodium(III)chloride (DPPZPHEN) demonstrate that such octahedral
      rhodium complexes are viable "photo-cisplatin" reagents.

PMID- 15876134
TI  - Doctors and nurses in outback Australia: living with bush initiatives.
AB  - This qualitative in-depth study investigates the work and life experiences of 18
      female doctors and nurses in remote Australia. The study begins to unravel some
      of the events and relationships in the women's lives that keep them working and
      living in remote areas. The study also examines social and working conditions
      that cause the women to leave, and concludes that action must be taken at both
      government and local levels to support female health professionals who work in
      remote locations. This may be achieved by the means of a health promotion action
      model to underpin such initiatives as the 1999 Commonwealth Government 'fly-in
      fly-out' initiative, in which sessional female doctors provide women's health
      services in remote areas.

PMID- 15876135
TI  - Women, isolation and bush babies.
AB  - This qualitative study illuminates the health care and life experiences of women
      on isolated pastoral stations in remote Australia who look after babies and
      children. The women care for their families in singular isolation, caught in the
      culture of the bush. Adaptation to or retreat from such a life is a unique
      process for each woman.

PMID- 15876136
TI  - Towards more rural nursing and allied health services: current and potential
      rural activity in the Division of Health Sciences of the University of South
      Australia.
AB  - INTRODUCTION: As part of Australia's regional health strategy, one of the
      recently introduced initiatives aims to increase the range of allied health and
      nursing services available in rural and remote communities, reflecting the
      growing recognition of allied health rural and remote workforce problems. While
      some programs focus on increasing services in rural and remote communities, long
      term solutions depend in part on the actions and activities of training
      institutions. Medical schools are being encouraged and financed to provide more
      rural exposure for undergraduates, but less is known about such programs for
      allied health and nursing students. METHODS: A survey of the seven Schools
      comprising the Division of Health Sciences of the University of South Australia
      was undertaken to determine the extent of rural exposure in undergraduate
      education, research, and service support. RESULTS: Five Schools (71%) offer rural
      placements for undergraduates, four (57%) are doing rural research and three
      (43%) provide some services to rural communities. Contingent on appropriate
      resources, all Schools expressed a strong desire to substantially increase the
      amount of rural activity. CONCLUSION: This research highlighted the paucity of
      data in this area and suggests the need for a national survey.

PMID- 15876137
TI  - Playing their part: the role of physical activity and sport in sustaining the
      health and well being of small rural communities.
AB  - It is widely recognised that the health of rural Australians is poor in
      comparison with their urban counterparts. Similarly, the role played by physical
      activity in maintaining health has been well researched and is well documented.
      However, little appears to have been published in recent years about the links
      between physical activity and health in rural communities. The objective of this
      article was to begin to address that gap. To achieve this, the article drew on
      research conducted in two small rural communities in Victoria Australia, and
      highlighted the role that physical activity and sport played in sustaining the
      health and wellbeing of individuals and communities in rural areas. Taking the
      World Health Organisation's definition of health (a state of complete physical,
      mental and social well-being and not merely the absence of disease) as its
      measure, the paper highlighted the many ways in which physical activity and sport
      in rural communities contribute to physical health, mental wellbeing and social
      cohesiveness. Based this finding, the authors suggest that physical activity and
      sport make a significant contribution to the health and wellbeing of rural people
      and their communities and suggest that further research is necessary to better
      define this apparent contribution.

PMID- 15876138
TI  - Exploring indicators of experiential place integration in a sample of Queensland
      rural practitioners: a research note.
AB  - INTRODUCTION: Until recently, the focus on the universal problem of insufficient
      medical practitioners in rural areas had been on training and recruitment. Many
      of the rural workforce strategies in Australia targeted selection of medical
      students, medical curricula, postgraduate training and retraining experienced
      urban graduates. To date, there is little consistent evidence that the rural
      workforce situation in Australia is improving. The decision to remain in rural
      practice appears to be a dynamic equilibrium of positive and negative factors,
      and issues such as overwork and poor adaptation to role changes easily upset this
      equilibrium. AIM: To perform a scoping exploratory post facto review of interview
      data with a view to establishing the potential for a dedicated prospective study
      of rural GP retention. METHODS: Theoretical construct of 'dimensions of
      integration' was used in a post facto review of in-depth interview transcripts of
      17 medical practitioners who had left rural practice. The construct posited
      integration as an active developmental process based on three 'principles'-
      security, freedom and identity--which together form the basis of practitioner
      retention. A series of 'dimensions' (n = 27) exists within each of these
      principles. RESULTS: Many of the 27 dimensions were found to be absent,
      particularly for practitioners who left before they originally intended. In some
      cases, apparently well-established practitioners (in terms of numbers of
      dimensions present) left because of some external 'pulling factor'. Dimensions
      related to practitioner security were generally most often missing. CONCLUSION:
      The potential for a dedicated prospective study was established.

PMID- 15876139
TI  - Opening farm gates: community as educator.
AB  - This paper presents the experience of five undergraduate Bachelor of Nursing
      students who undertook a clinical practice placement in a rural community. This,
      our first engagement with nursing, was a profound learning experience. We did not
      expect the intense contributions the rural community as a whole would make to our
      understandings of rural health care in general, and rural nursing in particular.
      Initially, we felt like outsiders to the rural community as well as the
      profession of nursing. The interwoven nature of community relationships combined
      with our acute sense of being highly visible in the township led to us developing
      a sense of vulnerability. We believed we needed to portray a professional image
      during all social interactions with the community and this compounded our
      insecurities during the clinical placement. Before long, we found the rural
      population embracing and very supportive of our placement. However, we found
      ourselves questioning whether we would return to a rural community to work as
      nurses on the basis of our lack of privacy during this time.

PMID- 15876140
TI  - Evidence-based rural general practice: barriers and solutions in South Australia.
AB  - INTRODUCTION: This paper reports on research to ascertain the views of general
      practitioners (GPs) practising in rural and remote areas of South Australia, on
      evidence-based medicine (EBM). It follows our previous paper that identified,
      through a literature search, the key issues in moving towards EBM in general
      practice in these areas1. The objective of the paper was to identify perceived
      barriers and potential solutions to evidence-based general practice in rural and
      remote South Australia. METHODS: An interview survey was conducted in the year
      2000 at 89 of 104 GPs' (86%) surgeries in three rural Divisions of General
      Practice in South Australia. RESULTS: EBM was viewed positively by 85%, and 94%
      reported practising EBM. However, barriers to EBM were identified by 84% and four
      key themes were identified. GP-related barriers identified by 60% included
      difficulty finding, appraising and applying evidence and lack of time to read,
      reflect and update practice. Patient related barriers (23%) included an apparent
      conflict between some patients' expectations and evidence. Environmental barriers
      (43%) related to remoteness included high workload, limited information and poor
      resources for continued medical education. Resource related barriers included a
      lack of computer hardware and software and slow, unreliable and expensive
      Internet access (14%). Potential solutions were suggested by 82%. The most
      frequent was improved hardware, software and Internet access (41%). Only 19%
      suggested formal training for GPs, while 26% suggested improved clinical practice
      guidelines and 23% suggested non-Internet based dissemination of information
      including a service to provide evidence-based answers to clinical problems.
      CONCLUSION: EBM was viewed positively by the surveyed GPs and many believed they
      already practised it. Most identified barriers to full and effective use of EBM
      but also suggested solutions.

PMID- 15876141
TI  - Rural residents' utilisation of health and visiting specialist health services.
AB  - INTRODUCTION AND OBJECTIVES: The purpose of the study was to identify the
      demographic and health service characteristics impacting on rural residents'
      utilisation of health and visiting specialist services in Western Australia.
      METHOD: Focus group discussions were held with an age-stratified, randomly
      selected group of forty-eight residents in four rural Western Australian towns
      between May and June 2000. RESULTS: Discussions revealed a preference to use
      local health services for basic care and to travel for the treatment of major or
      severe illnesses. The focus group participants supported visiting specialist
      services, indicating a willingness to use them for consultations, diagnostic and
      minor procedures. Utilisation of visiting services was conditional on the
      provision of information on specialist reputation, service outcomes, integration
      of the service into local facilities, and recommendation by the local general
      practitioner. CONCLUSION: Numerous factors influence the service-seeking
      behaviour of rural patients. These factors need to be recognised and considered
      in the design and promotion of resident and visiting specialist services if the
      migration for health care is to be rationalised.

PMID- 15876142
TI  - Reforms on medical education: the case of Kyrgyzystan.
AB  - INTRODUCTION: The Central Asian republics of the former Soviet Union gained their
      independence in 1991. Soon after this event, reforms in health care were planned
      in many of these countries. In Kyrgyzistan, the reforms included a mandatory
      health insurance system, a new provider payment system, licensing and
      accreditation, a national drug policy and rationalization of ambulatory services.
      Multi-profile policlinics, or family medicine group practices were established.
      Reforms in health care are not always accompanied by changes in medical
      education, and so medical knowledge may lag behind that in other countries. This
      is especially prominent in rural areas, where new practices and regulations may
      arrive late, and are often misunderstood. The reforms in Kyrgyzistan necessitated
      a change in undergraduate medical education. The educational reform consisted of
      a unification of the separate tracks for pediatrics, medicine and public health
      into one track of general medicine; the introduction of teaching of patho
      physiology according to body systems; the establishment of clinical clerkships;
      and a proposal for rotating internship. METHODS: World Health Organisation sent
      teams to Kyrgyzistan to work with the local committees as facilitators for the
      implementation of the health-care reform. This paper is based on the experience
      of the authors in conducting two such missions directed at the synergistic reform
      in medical education. RESULTS: VISIT 1: Changes to the curriculum were suggested.
      It was decided not to recommend teaching in rural primary care settings at that
      stage, due to logistical difficulties. This subject was to be addressed at a
      later stage because medical services in rural areas were scarce. VISIT 2: Among
      other interventions, the encouragement of doctors to practice in rural areas was
      discussed in detail, but the teachers of the medical school were not receptive to
      the idea of sending medical students to rural clinics. This was to be addressed
      at some time in the future. CONCLUSION: The changes were aimed at facilitating
      the introduction of family medicine as a specialty and strengthenning primary
      care, although measures to incorporate rural practice in the reform proved
      difficult to achieve. Reform in medical education can only be justified if it
      will contribute to the improvement of the health of the population. In order to
      achieve this goal, the production of better physicians must be assured. In
      Kyrgyzistan, it was hoped that improved graduates would be the resource for the
      development of family medicine as a recognized specialty, with the potential to
      improve the health status of the whole population.

PMID- 15876143
TI  - Proposed telemedicine booth.
AB  - Change is inescapable. For the rural and remote population the world over,
      changes to society's view of doctors, and to doctors' view of their role and
      place in society have lead to a decline in the number of rural practitioners.
      This personal view of change, and the impact of technology on change, comes from
      the Grampian area of Scotland, where the traditional remote community of
      villagers, school, doctor, bank and church is in rapid decline. In response to
      the steady reduction in medical services to remote areas, a telemedicine booth (a
      site where a variety of technologies can be brought together) has been proposed
      to support generic health workers provide acceptable and effective care to
      isolated patients. Not only will the technology enable patient consultation with
      a distant physician, if it is developed in partnership with a commercial firm, it
      also offers the possibility of an 'electronic community' where medical care and
      other social or commercial services may be delivered in tandem, at a distance.
      This idea, that addresses the needs of remote populations and their health
      workers the world over, was presented to the 5th WONCA World Conference on Rural
      Health in Melbourne, Australia in 2001 by the author, a medical practitioner and
      health administrator from Grampian, Scotland.

PMID- 15876146
TI  - The ethics of international recruitment.

PMID- 15876144
TI  - Health-care choices--the right of all Australians.

PMID- 15876147
TI  - Working abroad.

PMID- 15876151
TI  - Radiation-induced senescence-like terminal growth arrest in thyroid cells.
AB  - Premature senescence may play an important role as an acute, drug-, or ionizing
      radiation (IR)-inducible growth arrest program along with interphase apoptosis
      and mitotic catastrophe. The aim of the study was to evaluate whether IR can
      induce senescence-like phenotype (SLP) associated with terminal growth arrest in
      the thyroid cells, and if so, to evaluate impact of terminal growth arrest
      associated with SLP in intrinsic radiosensitivity of various thyroid carcinomas.
      The induction of SLP in thyroid cells were identified by: (1) senescence
      associated beta-galactosidase (SA-beta-Gal) staining method, (2) dual-flow
      cytometric analysis of cell proliferation and side light scatter using vital
      staining with PKH-2 fluorescent dye, (3) double labeling for 5-bromodeoxyuridine
      and SA- beta-Gal, (4) Staining for SA-beta-Gal with consequent antithyroglobulin
      immunohistochemistry. IR induced SLP associated with terminal growth arrest in
      four thyroid cancer cells lines and in primary thyrocytes in time- and dose
      dependent manner. Analysis of relationship between induction of SLP and
      radiosensitivity revealed a trend in which more radioresistant cell lines
      strongly tended to show lower specific SLP yields (r = -0.93, p = 0.068). We find
      out that SA-beta-Gal staining is detectable in irradiated ARO xenotransplants,
      but not in control tumors. We, therefore, conclude that induction of SLP with
      terminal growth arrest contribute to the elimination of clonogenic populations
      after IR.

PMID- 15876152
TI  - Postnatal changes of steroid receptor coactivator-1 immunoreactivity in rat
      cerebellar cortex.
AB  - Steroid receptor coactivator-1 (SRC-1) interacts with nuclear hormone receptors
      (NRs) to mediate their action in a ligand-dependent manner. Among such ligands,
      thyroid hormone (TH) is particularly crucial for brain development. The
      expression of many TH target genes is regulated by TH only for a limited critical
      period, although TH receptor (TR) expression is not greatly altered after such
      period. To alter TH sensitivity, other factors may be involved. We thus examined
      the changes in SRC-1 expression during postnatal development in the rat
      cerebellum by immunohistochemistry and Western blotting. Strong SRC-1
      immunoreactivity (IR) was constantly seen in Purkinje cell from postnatal days
      (P) 2 to P30. SRC-1 IR was also constantly observed in the internal granule cell
      layer. However, it was negative in the external granule cell layer at P2 and P7,
      whereas a weak IR was detected in the premigratory zone at P15. SRC-1 IR was
      detected in the molecular layer after P15. These results indicate that although
      TR is almost ubiquitously expressed in the developing cerebellum, the TH
      sensitivity could vary in each subset of cells. By Western blotting, SRC-1
      protein level was greatest at P15, at which time TH action may be obvious. Taken
      together, the differential expression of SRC-1 may be crucial in mediating TH
      action during cerebellar development.

PMID- 15876153
TI  - BRAF mutations are uncommon in papillary thyroid cancer of young patients.
AB  - Mortality is low for young patients (younger than 21 years) with papillary
      thyroid cancer (PTC), and different mutations might contribute to this. Previous
      studies detected ret/PTC rearrangements more frequently in PTC from children than
      adults, and recent reports describe a high incidence of BRAF T1796A transversion
      in adult PTC. However, BRAF mutations have not been adequately studied in PTC
      from young patients. We amplified and sequenced segments of the BRAF gene
      spanning the T1796A transversion site in 14 PTC from patients 10-21 years of age
      (mean, 17.5 +/- 3.5 years). The PTC (7 = class 1; 5 = class 2; 1 = class 3)
      ranged from 0.7-2.9 cm in diameter (mean, 1.4 +/- 0.75 cm). None of them (0/14)
      contained BRAF T1796A and none recurred (mean follow-up, 66 +/- 40 months). This
      incidence of BRAF T1796A is significantly less than that reported for adult PTC
      (270/699, 38.6%, p = 0.0015) in several series. None of our PTC (0/10) contained
      ras mutations, but 7/12 (58%) contained ret/PTC rearrangements. We conclude that
      BRAF mutations are less common in PTC from young patients, and ret/PTC
      rearrangements were the most common mutation found in these childhood PTC.

PMID- 15876155
TI  - Selective agonists and antagonists to thyroid hormone action.
AB  - Selective thyromimetics have been designed and shown to exhibit some of the
      beneficial effects of thyroid hormones, such as lowering of cholesterol and
      weight reduction, without the adverse thyroid hormone action on muscle, bone, and
      heart rate. Progress has also been made in attempting to treat hyperthyroidism by
      synthesizing antagonists that block thyroid hormone action, at the level of the
      thyroid hormone receptor or of the thyrotropin receptor. Clinical trials are
      still awaited, however, to verify whether these potentially promising agents will
      indeed prove to be of clinical therapeutic value.

PMID- 15876154
TI  - Low prevalence of RET rearrangements (RET/PTC1, RET/PTC2, RET/PTC3, and ELKS-RET)
      in sporadic papillary thyroid carcinomas in Taiwan Chinese.
AB  - Somatic rearrangement of the tyrosine kinase receptor RET is restricted to
      papillary thyroid carcinoma (PTC). The prevalence of RET/PTC1, RET/PTC2, and
      RET/PTC3 has been found to vary between 0% and 20% in most series of sporadic
      (nonradiation-induced) PTCs analyzed by type-specific reverse transcription
      polymerase chain reaction (RT-PCR) alone. However, high prevalence reported from
      Taiwan (6 out of 11, 55%) indicates RET rearrangement is an important genetic
      lesion underlying the development of PTC in Taiwan. Because the high prevalence
      of RET rearrangements in Chinese patients was particularly striking, we were
      prompted to reexamine chimeric transcripts of RET/PTC1, RET/PTC2, and RET/PTC3
      using the same experimental designs in a larger number of cases in the same
      population. RT-PCR was performed to amplify fusion products of RET/PTC1,
      RET/PTC2, RET/PTC3, and ELKS-RET from frozen tissue of 105 sporadic PTCs. RT-PCR
      was also performed with two different primer sets for RET/PTC1, RET/PTC2, and
      RET/PTC3 followed by Southern hybridization in the first 62 tumors. In our study,
      RET/PTC1, RET/PTC2, and RET/PTC3 oncogenes were found in only 7 of 105 (7%)
      sporadic PTCs. Of these tumors, 3 involved RET/PTC1 and 4 involved RET/PTC3. No
      RET/PTC2 rearrangements were observed. In the first 62 tumor samples, another two
      different primer sets for each rearrangement also gave concordant results.
      Furthermore, application of Southern hybridization in these 62 PTCs did not
      identify additional tumor harboring RET chimeric transcripts. We identified one
      tumor as having an ELKS-RET rearrangement (1 of 105, 1%). In conclusion, we
      detected RET rearrangements in 8 of 105 (8%) sporadic PTCs in Taiwan, a much
      lower prevalence than previously reported for this population but comparable to
      those reported in other nations using similar methodology. RET chimeric oncogenes
      only account for a small fraction of PTCs in Taiwan.

PMID- 15876156
TI  - Successful treatment for recurrent painful Hashimoto's thyroiditis by total
      thyroidectomy.
AB  - Painful Hashimoto's thyroiditis is an atypical variant of Hashimoto's thyroiditis
      characterized by thyroid pain and fever. In patients with this condition, anti
      inflammatory agents are not always effective as in those with subacute
      thyroiditis. Therefore, long-term pain management is an important issue. We
      report herein four cases of painful Hashimoto's thyroiditis requiring total
      thyroidectomy to relieve thyroid pain and histologic findings of the thyroid
      gland. All patients had high titers of anti-thyroperoxidase (TPO) and
      thyroglobulin antibodies. Three were hypothyroid, and the other was euthyroid.
      During the first visit, four patients had fever and/or thyroid pain with elevated
      C-reactive protein or erythrocyte sedimentation rate, and they were treated with
      oral corticosteroids given continuously or intermittently for 9 to 48 months.
      Because a reduction or discontinuation of corticosteroids caused recurrent
      painful attacks, the decision was made to perform surgery. After total
      thyroidectomy, their symptoms disappeared. The histopathologic characteristics of
      these hypothyroid cases were advanced fibrosis and destructive thyroid
      architecture. One euthyroid case showed a mild fibrous change and the presence of
      foreign body type giant cells. In conclusion, total thyroidectomy is the
      effective and reliable treatment for patients with recurrent painful Hashimoto's
      thyroiditis. Pathologic characteristics include advanced fibrosis and destructive
      thyroid architecture.

PMID- 15876157
TI  - What is the role of pendrin?

PMID- 15876158
TI  - Maternal thyroid disorders and preterm birth: another piece of the puzzle?

PMID- 15876160
TI  - Orbital gallium-67 scintigraphy in Graves' ophthalmopathy: a disease activity
      parameter that predicts the therapeutic response to immunosuppressive treatment.
AB  - In this study, orbital gallium-67 citrate ((67)Ga) scintigraphy was evaluated as
      a disease activity parameter that can predict the therapeutic response to
      immunosuppressive treatment in Graves' ophthalmopathy. Orbital scintigraphic
      analysis was performed on 32 patients demonstrating moderate to severe Graves'
      ophthalmopathy. Single-photon emission computed tomography (SPECT) images were
      obtained 48 hours after intravenous injection of 148 MBq of radioactive (67)Ga
      complex, and orbit/occipital (O/Occ) ratios were calculated to correct the
      background activity. Intravenous methylprednisolone was given as
      immunosuppressive treatment to 24 patients (group 1) and 8 patients were followed
      up without any treatment and evaluated as controls (group 2). Orbital (67)Ga
      scintigraphy was repeated in all patients after 6 months to analyze the changes
      in clinical findings and orbital (67)Ga accumulation. In Group 1, the mean +/-
      standard deviation (SD) (67)Ga O/Occ ratio of responders (2.23 +/- 0.2, 16 cases)
      was statistically different from nonresponders (1.49 +/- 0.1, 8 cases, p <
      0.001). Additionally, the corticosteroid treatment provided a significant
      decrease in orbital (67)Ga accumulation in responders (p < 0.001), however, it
      did not change statistically in nonresponders (p:0.13). In group 2, the patients
      did not demonstrate clinical improvement and orbital (67)Ga uptake did not change
      after the follow-up period (p:0.81). The receiver-operator-characteristic curve
      showed that the best threshold for discriminating responder and nonresponder
      groups was 1.70 (sensitivity, 94%; specificity, 88%). This study demonstrated
      that orbital (67)Ga scintigraphy may be a useful imaging technique in predicting
      the therapeutic response to immunosuppressive treatment in Graves'
      ophthalmopathy.

PMID- 15876159
TI  - The thyroid and pregnancy: a novel risk factor for very preterm delivery.
AB  - The major cause of neonatal mortality and morbidity is preterm delivery in
      general (< 37 completed weeks), and especially very preterm delivery (< 32
      completed weeks). The objective of this study is to determine if either thyroid
      hormonal dysfunction and/or the presence of thyroid autoantibodies in the mother
      are associated with an increased risk of preterm and/or very preterm delivery.
      Data were collected prospectively and analyzed as a nested-case control study.
      There were 953 delivered gravidas enrolled between 1996 and 2002. Samples were
      collected at entry to care and stored at -70 degrees C. Cases included all women
      with preterm delivery (n = 124). Controls (n = 124) were randomly selected from
      among the 829 women who delivered at term (> 37 completed weeks). All samples
      were assessed for thyroid stimulating hormone, thyroperoxidase antibody, and
      thyroglobulin antibody. Gravidas with high thyrotropin (TSH) levels had a greater
      than threefold increase in risk of very preterm delivery. In some analyses,
      gravidas who tested positive for thyroglobulin antibody at entry to prenatal care
      also had a better than twofold increased risk of very preterm delivery. There
      were no significant associations between TSH level or thyroglobulin antibody
      positivity and the risk of moderately preterm delivery.

PMID- 15876161
TI  - Iodine nutrition, nodular thyroid disease, and urinary iodine excretion in a
      German university study population.
AB  - We determined the influence of different nutritional factors on the urinary
      iodine excretion in an East German university population. First, we assessed
      iodine excretion in spot urine samples. Second, we measured iodine content in the
      university canteen meals, where approximately 20% of the probands had regular
      meals. Third, we used a special food questionnaire to assess for other sources of
      nutritional iodine intake, namely iodine tablets, fish consumption, etc. Fourth,
      we determined the actual prevalence of goiter and thyroid nodules in our probands
      by high-resolution ultrasonography. The mean urinary iodine excretion in our
      cohort was 109 +/- 81 microg/g level indicating a borderline adequate iodine
      intake (100-200). The frequency of thyroid nodules was 30% and the frequency of
      goiter 11%. Thyroid volumes greater than 18 mL and 25 mL were considered to be
      enlarged in adult women and men respectively. Urinary iodine excretion was not
      related to the presence of goiter or thyroid nodules. In addition urinary iodine
      excretion did not vary with regular consumption of canteen meals, which contained
      approximately 50% of the daily recommended iodine intake. In contrast probands
      with regular supplementary intake of iodine tablets had significantly higher
      values of urinary iodine excretion (169 +/- 130 microg/g) compared to
      participants without (103 +/- 87 microg/g). No other single nutritional factor
      (e.g., salt, milk, or bread) had a statistically significant impact on urinary
      iodine excretion or was able to raise the urinary iodine excretion above the
      level of marginal iodine deficiency. In summary, the nutritional iodine intake in
      a Saxonian study population was found to be close to the margin of iodine
      deficiency. This shows insufficient supplementation of iodine through iodized
      salt/industrialized food production.

PMID- 15876162
TI  - Recombinant human thyrotropin is helpful in the follow-up and 131I therapy of
      patients with thyroid cancer: a report of the results and benefits using
      recombinant human thyrotropin in clinical routine.
AB  - There is no doubt that the availability of recombinant human thyrotropin (rhTSH)
      is one of the milestones in the management of patients with differentiated
      thyroid cancer (DTC). It offers the opportunity to obtain representative serum
      thyroglobulin (Tg) levels and diagnostic whole-body scanning (Dx WBS) with 131I
      under adequate TSH elevation, while the patient continues to receive thyroid
      hormone. But rhTSH is also used with success in the treatment of local
      recurrences and distant metastases. In this retrospective analysis we were able
      to show that our excellent clinical experiences with the use of rhTSH (rare side
      effects and high compliance) could also be demonstrated by sufficiently elevated
      TSH levels and representative stimulated Tg measurements. Since April 2001 most
      of the patients with thyroid cancer in our hospital have undergone diagnostic
      examination (205 patients underwent 319 examinations) and 131I therapy (a total
      of 68 treatments) with rhTSH stimulation excluding the first radioiodine ablation
      of remnants after initial thyroidectomy. Our results show that under rhTSH
      stimulation 83.5% (diagnostic group) and 88% (therapy group) of our patients with
      DTC obtained a TSH level of greater than 80 mU/L after two injections of rhTSH
      (Thyrogen, Genzyme Corp., Cambridge, MA) 0.9 mg intramuscularly 24 hours and 48
      hours before the administration of 131I. Only 2.3% (diagnostic group) and 0%
      (therapy group) demonstrated TSH levels less than 50 mU/L. Serum Tg levels under
      rhTSH-stimulated conditions showed that in 81.2% the serum Tg maximum was
      obtained on day 5. Because of the costs associated with periodically rhTSH
      assisted Tg testing and based on the data of other studies we are now testing
      mainly on day 5 to identify residual tumor mass and to compare these Tg levels in
      the follow-up. Our experience demonstrates that the administration of rhTSH is a
      safe, effective, and-from an economic point of view- valuable tool in the
      management of patients with DTC.

PMID- 15876163
TI  - Is the resistance of large conduit arteries also decreased in thyrotoxic patients
      with Graves' disease?
AB  - Longitudinal arterial resistance (RL) originates during blood flow in large
      conduit arteries while peripheral resistance (RP) reflects the tension of
      arterioles. Using a new noninvasive ultrasonic system of assessment of mechanical
      properties of arterial walls, we aimed to discover whether both RL and RP are
      affected by excess of thyroid hormones (TH). We compared two groups: hyperthyroid
      (Graves' group, n = 25) and euthyroid (control group, n = 23). RL and RP values
      were obtained from the analysis of the four-element lumped parameters model
      describing the vascular input impedance. The vascular input impedance was
      determined on the basis of simultaneous measurements of blood pressure, blood
      flow and arterial diameter using oscillometric and ultrasonic methods. RL and RP
      were lower in the Graves' group (3.71 +/- 1.98 versus 4.49 +/- 1.81
      10(8)kgm(4)s(1), p < 0.05 and 8.43 +/- 3.56 versus 11.23 +/- 2.69 0(8)kgm(4)s(1),
      p < 0.00002, respectively). There was strong correlation between RP and TH in the
      Graves' group (r(s)= -0.6710, p = 0.000001 for RP and free triiodothyronine
      (FT3); r(s)= -0.4683, p < 0.001 for RP and free thyroxine [FT4]). This
      relationship remained significant after the statistical correction for total
      cholesterol (r(p)= -0.7064 p = 0.0000001 for RP and FT3). No similar correlation
      between RL and TH was found what suggests a different character of relations
      between TH and RL and between TH and RP.

PMID- 15876164
TI  - Papillary thyroid carcinoma associated with amyloid goiter.

PMID- 15876165
TI  - Celiac disease presenting as resistant hypothyroidism.
AB  - The high prevalence of celiac disease in patients with autoimmune hypothyroidism,
      compared to the general population, has been well documented but screening for
      celiac disease is not recommended as yet in otherwise asymptomatic hypothyroid
      patients. In recent years the high prevalence of undiagnosed celiac disease in
      the general population, largely as a result of the many atypical manifestations
      of the disease, has become apparent. We report the case of a 58-year-old woman
      with autoimmune hypothyroidism who was initially suspected of having celiac
      disease on the basis of apparent resistance to levothyroxine therapy, and who had
      no other clinical or laboratory clues to suggest the diagnosis. Cases of
      undiagnosed celiac disease causing levothyroxine malabsorbtion have previously
      been described, but all previous cases had other obvious manifestations of the
      disease. We believe that this atypical presentation of celiac disease warrants
      further attention, and that the diagnosis of celiac disease should always be
      considered in patients requiring higher than expected doses of thyroid hormone
      replacement, even in patients with normal bowel habit, and no other apparent
      manifestations of the disease.

PMID- 15876166
TI  - Two novel mutations in the sixth transmembrane segment of the thyrotropin
      receptor gene causing hyperfunctioning thyroid nodules.
AB  - Autonomously functioning thyroid nodules (AFTNs) can present as hyperfunctioning
      adenomas or toxic multinodular goiters. In the last decade, a large number of
      activating mutations have been identified in the thyrotropin receptor (TSHR) gene
      in autonomously functioning thyroid nodules. Most have been situated close to, or
      within the sixth transmembrane segment and third intracellular loop of the TSHR
      where the receptor interacts with the Gs protein. In this study we describe two
      novel mutations in the sixth transmembrane segment of the TSHR causing
      hyperfunctioning thyroid nodules. Genomic DNAs were isolated from four
      hyperfunctioning thyroid nodules, normal tissues and peripheral leukocytes of two
      patients with toxic multinodular goiter. After amplifying the related regions,
      TSHR and G(s)alpha genes were analyzed by single-strand conformation polymorphism
      (SSCP) analysis. The precise localization of the mutations was identified by
      automatic DNA sequence analysis. Functional studies were done by site-directed
      mutagenesis and transfection of a mutant construct into COS-7 cells. We
      identified two novel TSHR mutations in two hyperfunctioning thyroid nodules:
      Phe631Val in the first patient and Iso630Met in the second patient. Both mutant
      receptors display an increase in constitutive stimulation of basal cyclic
      adenosine monophosphate (cAMP) levels compared to the wild-type receptor. This
      confirms that these mutant receptors cause hyperfunctioning thyroid nodules.

PMID- 15876167
TI  - Successful intravenous immunoglobulin therapy for resistant inflammatory
      pseudotumor of the orbit.

PMID- 15876168
TI  - No politics please--we are thyroidologists.

PMID- 15876172
TI  - Sidney L. Saltzstein, MD, MPH receives 2004 Margaret Hay Edwards Achievement
      medal.

PMID- 15876173
TI  - Teaching cancer management to primary care health staff: the first experiences
      gained from Crete.

PMID- 15876174
TI  - Conflicts of interest/commitment.

PMID- 15876177
TI  - The impact of predoctoral pediatric oncology education.
AB  - BACKGROUND: Our Pediatric Oncology Education Program gives predoctoral students
      the opportunity to gain knowledge and experience to enable them to consider
      careers in cancer research, clinical practice, and related areas. METHODS:
      Students are matched with a faculty mentor with similar research interests and
      participate in the mentor's ongoing research program. They attend ongoing
      institutional clinical and basic research conferences, as well as a Lunch & Learn
      seminar series designed specifically for them. They give a PowerPoint
      presentation on their research project in the Lunch & Learn series and submit a
      report on their research project written in the style of a journal in which their
      mentor publishes. RESULTS: Follow-up for 98.4% of the 807 program participants
      (1978-2004) indicates that of those who have finished their academic degree work,
      87.9% have a doctorate, including 79.8% of the under-represented minority
      participants. 73.6% (594) of former participants are still in training. 32.3%
      (261) have a pediatrics or family medicine career or career goal, 24.3% (196)
      have a cancer-related career or career goal, and 4.8% (39) are already in a
      cancer-committed career. Approximately one-half of recent participants who
      returned for a second or third appointment have a cancer-related career goal.
      CONCLUSIONS: Results suggest that predoctoral pediatric oncology research
      experience fosters cancer-related career goals.

PMID- 15876178
TI  - Impact of the recent reduction in working hours (the 80 hour work week) on
      surgical resident cancer education.
AB  - BACKGROUND: Resident work hours were recently reduced to 80 hours per week by a
      mandate from the Accreditation Council for Graduate Medical Education and
      subsequent Federal law (HR 3236). This mandate became effective July 1st, 2003.
      We sought to determine any impact this change had on perceived and real resident
      cancer education and knowledge. METHODS: Of the total 85 residents in our large,
      university-based surgical training program, we focused on the 40 who had been in
      the clinical program (rather than research) before and after the work hour
      reduction. Perceived impact on cancer education was determined by survey, and
      real impact by before (2002) and after (2004) scores on the overall and cancer
      specific portion of the annual American Board of Surgery In-Training Examination
      (ABSITE). RESULTS: All eligible residents responded to the survey. The majority
      (83% to 85%) indicated that exposure to cancer patients on wards and in clinics
      remained the same. Thirty percent felt that their exposure to cancer operations
      and tumor boards had decreased; 60% to 65% felt that exposure to these activities
      were unchanged. Approximately half of residents reported an increase in their
      cancer-related reading and Internet learning activities--the other half felt they
      had not changed. The majority (88%) reported no change in their participation in
      extraprogrammatic cancer-related continuing medical education activities. Of the
      survey responders, 23 had completed the ABSITE in both 2002 and 2004; their mean
      scores between the 2 time periods increased by 7% for the overall test and
      decreased by 3% for the cancer-specific portion. CONCLUSIONS: Overall, the recent
      reduction in work hours does not appear to have changed residents' experience
      with cancer patient care, although possible early reductions in attendance at
      cancer operations and tumor boards merits further study and possibly future
      schedule changes. The reported perceived increase in cancer-related reading and
      Internet learning has not yet translated into improved test scores.

PMID- 15876179
TI  - Educational needs of general practitioners in palliative care: outcome of a focus
      group study.
AB  - BACKGROUND: The objective of this study was to identify the general
      practitioner's perception of educational needs in palliative care. METHOD: A
      qualitative study with focus groups was performed. RESULTS: General practitioners
      estimate palliative care as an important and valuable part of primary care.
      Nevertheless, they consider their coordinating role as a course with increasing
      obstacles. Pain, nausea, dysphagia, delirium, insomnia, anxiety, and depression
      were mentioned frequently as symptoms difficult to deal with in palliative care.
      Also, psychosocial issues such as communication, bereavement, and defense
      mechanisms were subject to discussion in the focus groups. Ethical issues such as
      euthanasia were mentioned as the most complex subject in palliative care.
      CONCLUSIONS: General practitioners experience difficulties with their
      coordinating role in palliative care. With more basic knowledge and skills in
      communication, but also with consultation, their roles as coordinators of
      palliative care in primary care will improve. Reflection and deepening of ethical
      values are necessary conditions for an optimal functioning.

PMID- 15876180
TI  - Primary care providers' concerns and recommendations regarding mammography
      screening for older women.
AB  - BACKGROUND: Morbidity and mortality from breast cancer increase with age;
      however, mammography screening does not reflect this increased risk for older
      women. Lack of provider recommendation is a major barrier to screening. METHODS:
      This is a descriptive study of mammography screening recommendations of community
      primary care providers in North Carolina (N = 96) participating in a National
      Cancer Institute funded research project. Providers self-reported screening
      recommendations for typical patients of different ages and issues and concerns
      that might influence the decision. Chart reviews compared actual practices with
      policies stated. RESULTS: Of the providers, 51% recommended biannual, 45% annual
      for women ages 50 through 74; 4% recommended biannual, 80% annual, 5% did not
      recommend screening, and 10% had no general policy for women over 75. Cost,
      inconsistent guidelines, comorbidity, functional status, value of mammography,
      and patient resistance influenced screening recommendations. Chart review showed
      even lower rates of recommendation than self-reported figures. CONCLUSIONS:
      Although the use of screening mammography has increased over the past decade,
      older women are one of the last subgroups to derive benefit from this screening
      test. Our survey revealed lower rates for mammography referral in older women.
      The primary care provider appears to be essential to increasing participation for
      these older women in breast cancer screening.

PMID- 15876181
TI  - Incorporating cultural constructs and demographic diversity in the research and
      development of a Latina breast and cervical cancer education program.
AB  - BACKGROUND: Latino immigrants are at higher risk of death from breast and
      cervical cancer, necessitating effective cancer education interventions. METHODS:
      Qualitative and quantitative information was obtained from Latinos from Arkansas
      and New York City through focus groups and questionnaires. Findings were analyzed
      using the PEN-3 model. RESULTS: The results demonstrate a mechanism for creating
      a culturally competent program, Esperanza y Vida, through progressively analyzing
      the findings to define the key perceptions, enablers, and nurturers, then
      applying this information to construct program components to address appropriate
      health behavior and cultural components that address the specific needs of a
      diverse Latino population. CONCLUSION: Finding a systematic approach to
      incorporating and embracing sociocultural perspectives and constructs may
      effectively appeal to diverse Latino immigrants in the development of a cancer
      education intervention.

PMID- 15876182
TI  - Using theater to promote cancer education in Alaska.
AB  - BACKGROUND: Cancer, a rare disease in the 1950s, is now the leading cause of
      death among Alaska Natives (AN). METHODS: Building on AN rich traditions of
      storytelling to share knowledge and wisdom, a 45 minute play, Understanding, was
      developed to address cancer-related issues specific to AN. RESULTS: Written
      audience evaluations assessed the impact of this theater-based education. After
      seeing the play, 327 (94.5%) people reported feeling more comfortable talking
      about cancer, 265 (66.1%) shared that they had learned about cancer, and 234
      (61.7%) wrote healthy ways they intended to change their behavior. CONCLUSION: A
      postplay discussion provided an opportunity for the audience to share their
      stories, concerns, beliefs, and feelings.

PMID- 15876183
TI  - Communicating respectfully with American Indian and Alaska natives: lessons from
      the California Health Interview Survey.
AB  - Background. California is home to the largest number of American Indians in the
      United States, including large numbers of residents who are from tribes outside
      of the state, in addition to Alaska Natives. In 2000 to 2001, the California
      Health Interview Survey randomly surveyed, by telephone, approximately 54,122
      households throughout the state, focusing on public health and access to health
      care. Methods. American Indian and Alaska Native cultural competency training
      materials were developed for the data collection interviewers. Unique cultural
      and linguistic issues identified were (1) reservation dialect English, (2) the
      long pause, (3) slow speaking, (4) "walking on words," and (5) a brief review of
      the importance of collecting tribal heritage information. Conclusions. Since the
      successful implementation of the competency training, several researchers,
      practitioners, state agencies, and others have requested and implemented the
      training materials in their work. In this article, we review the training
      materials. We hope that these few tips will help others have successful
      experiences communicating respectfully with American Indian and Alaska Natives.

PMID- 15876187
TI  - In vivo functional characterization of the Escherichia coli ammonium channel
      AmtB: evidence for metabolic coupling of AmtB to glutamine synthetase.
AB  - The Escherichia coli AmtB protein is member of the ubiquitous Amt family of
      ammonium transporters. Using a variety of [14C]methylammonium-uptake assays in
      wild-type E. coli, together with amtB and glutamine synthetase (glnA) mutants, we
      have shown that the filtration method traditionally used to measure
      [14C]methylammonium uptake actually measures intracellular accumulation of
      methylglutamine and that the kinetic data deduced from such experiments refer to
      the activity of glutamine synthetase and not to AmtB. Furthermore, the marked
      difference between the K(m) values of glutamine synthetase calculated in vitro
      and those calculated in vivo from our data suggest that ammonium assimilation by
      glutamine synthetase is coupled to the function of AmtB. The use of a modified
      assay technique allows us to measure AmtB activity in vivo. In this way, we have
      examined the role that AmtB plays in ammonium/methylammonium transport, in the
      light of conflicting proposals with regard to both the mode of action of Amt
      proteins and their substrate, i.e. ammonia or ammonium. Our in vivo data suggest
      that AmtB acts as a slowly conducting channel for NH3 that is neither dependent
      on the membrane potential nor on ATP. Furthermore, studies on competition between
      ammonium and methylammonium suggest that AmtB has a binding site for NH4+ on the
      periplasmic face.

PMID- 15876189
TI  - How ancient is the adult swimming capacity in the lineage leading to Euchordates?

PMID- 15876188
TI  - Activation of RelA homodimers by tumour necrosis factor alpha: a possible
      transcriptional activator in human vascular endothelial cells.
AB  - In vascular endothelial cells, cytokines induce genes that are expressed in
      inflammatory lesions partly through the activation of transcription factor NF
      kappaB (nuclear factor-kappaB). Among the members of the NF-kappaB/rel protein
      family, homodimers of the RelA subunit of NF-kappaB can also function as strong
      transactivators when expressed in cells. However, the functional role of
      endogenous RelA homodimers has not been clearly elucidated. We investigated
      whether RelA homodimers are induced in cytokine-treated vascular endothelial
      cells. Gel mobility-shift and supershift assays revealed that a cytokine TNFalpha
      (tumour necrosis factor alpha) activated both NF-kappaB1/RelA heterodimers and
      RelA homodimers that bound to a canonical kappaB sequence, IgkappaB
      (immunoglobulin kappaB), in SV40 (simian virus 40) immortalized HMEC-1 (human
      dermal microvascular endothelial cell line 1). In HMEC-1 and HUVEC (human
      umbilical-vein endothelial cells), TNFalpha also induced RelA homodimers that
      bound to the sequence 65-2kappaB, which specifically binds to RelA homodimers but
      not to NF-kappaB1/RelA heterodimers in vitro. Deoxycholic acid, a detergent that
      can dissociate the NF-kappaB-IkappaB complex (where IkappaB stands for inhibitory
      kappaB), induced the binding of the RelA homodimers to 65-2kappaB from the
      cytosolic fraction of resting HMEC-1. Furthermore, TNFalpha induced the
      transcriptional activity of a reporter gene that was driven by 65-2kappaB in HMEC
      1. These results suggest that in addition to NF-kappaB1/RelA heterodimers,
      TNFalpha also induces RelA homodimers that are functionally active. Thus RelA
      homodimers may actively participate in cytokine regulation of gene expression in
      human vascular endothelial cells.

PMID- 15876190
TI  - Diverse developmental mechanisms contribute to different levels of diversity in
      horned beetles.
AB  - An ongoing challenge to evolutionary developmental biology is to understand how
      developmental evolution on the level of populations and closely related species
      relates to macroevolutionary transformations and the origin of morphological
      novelties. Here we explore the developmental basis of beetle horns, a
      morphological novelty that exhibits remarkable diversity on a variety of levels.
      In this study, we examined two congeneric Onthophagus species in which males
      develop into alternative horned and hornless morphs and different sexes express
      marked sexual dimorphism. In addition, both species differ in the body region
      (head vs. thorax) that develops the horn. Using a comparative morphological
      approach we show that prepupal growth of horn primordia during late larval
      development, as well as reabsorption of horn primordia during the pupal stage,
      contribute to horn expression in adults. We also show that variable combinations
      of both mechanisms are employed during development to modify horn expression of
      different horns in the same individual, the same horn in different sexes, and
      different horns in different species. We then examine expression patterns of two
      transcription factors, Distal-less (Dll) and aristaless (al), in the context of
      prepupal horn growth in alternative male morphs and sexual dimorphisms in the
      same two species. Expression patterns are qualitatively consistent with the
      hypothesis that both transcription factors function in the context of horn
      development similar to their known roles in patterning a wide variety of
      arthropod appendages. Our results suggest that the origin of morphological
      novelties, such as beetle horns, rests, at least in part, on the redeployment of
      already existing developmental mechanisms, such as appendage patterning
      processes. Our results also suggest, however, that little to no phylogenetic
      distance is needed for the evolution of very different modifier mechanisms that
      allow for substantial modulation of trait expression at different time points
      during development in different species, sexes, or tissue regions of the same
      individual. We discuss the implications of our results for our understanding of
      the evolution of horned beetle diversity and the origin and diversification of
      morphological novelties.

PMID- 15876191
TI  - Expression of Hoxa-11 and Hoxa-13 in the pectoral fin of a basal ray-finned fish,
      Polyodon spathula: implications for the origin of tetrapod limbs.
AB  - Summary Paleontological and anatomical evidence suggests that the autopodium
      (hand or foot) is a novel feature that distinguishes limbs from fins, while the
      upper and lower limb (stylopod and zeugopod) are homologous to parts of the
      sarcopterygian paired fins. In tetrapod limb development Hoxa-11 plays a key role
      in differentiating the lower limb and Hoxa-13 plays a key role in differentiating
      the autopodium. It is thus important to determine the ancestral functions of
      these genes in order to understand the developmental genetic changes that led to
      the origin of the tetrapod autopodium. In particular it is important to
      understand which features of gene expression are derived in tetrapods and which
      are ancestral in bony fishes. To address these questions we cloned and sequenced
      the Hoxa-11 and Hoxa-13 genes from the North American paddlefish, Polyodon
      spathula, a basal ray-finned fish that has a pectoral fin morphology resembling
      that of primitive bony fishes ancestral to the tetrapod lineage. Sequence
      analysis of these genes shows that they are not orthologous to the duplicated
      zebrafish and fugu genes. This implies that the paddlefish has not duplicated its
      HoxA cluster, unlike zebrafish and fugu. The expression of Hoxa-11 and Hoxa-13 in
      the pectoral fins shows two main phases: an early phase in which Hoxa-11 is
      expressed proximally and Hoxa-13 is expressed distally, and a later phase in
      which Hoxa-11 and Hoxa-13 broadly overlap in the distal mesenchyme of the fin bud
      but are absent in the proximal fin bud. Hence the distal polarity of Hoxa-13
      expression seen in tetrapods is likely to be an ancestral feature of paired
      appendage development. The main difference in HoxA gene expression between fin
      and limb development is that in tetrapods (with the exception of newts) Hoxa-11
      expression is suppressed by Hoxa-13 in the distal limb bud mesenchyme. There is,
      however, a short period of limb bud development where Hoxa-11 and Hoxa-13 overlap
      similarly to the late expression seen in zebrafish and paddlefish. We conclude
      that the early expression pattern in tetrapods is similar to that seen in late
      fin development and that the local exclusion by Hoxa-13 of Hoxa-11 from the
      distal limb bud is a derived feature of limb developmental regulation.

PMID- 15876192
TI  - Loss of ancestral genes in the genomic evolution of Ciona intestinalis.
AB  - Comparison of the predicted protein sets encoded by the complete genomes of two
      vertebrates (human and pufferfish), the urochordate Ciona intestinalis, three
      nonchordate animals, and two fungi were used to reconstruct a set of gene
      families present in the common ancestor of chordates. These ancestral families
      were much more likely to be lost in Ciona than in either vertebrate. In addition,
      of 256 duplicate gene pairs that arose by duplication prior to the most recent
      common ancestor of vertebrates and insects, one of the duplicate genes was four
      times as likely to be lost in Ciona as in the vertebrates. These results show
      that the genome of Ciona is not representative of the ancestral chordate genome
      with respect to gene content but rather shows derived features that may reflect
      adaptation of the specific ecological niche of urochordates.

PMID- 15876194
TI  - A delay in age at first mating results in the loss of future reproductive
      potential via apoptosis.
AB  - Women who delay childbearing risk subfertility. However, this loss of fertility
      is not a simple function of aging. Women who have had children early in life tend
      to maintain fertility longer, measured as a later age at menopause. But why
      should otherwise healthy women lose reproductive capacity? Loss of fertility
      independent of senescence, menopause, has been approached from two perspectives:
      evolution and development. Evolutionary biologists focus on how natural selection
      favors survival after reproductive ability has ceased, whereas reproductive
      biologists examine mechanisms by which women lose fertility with age and factors
      that influence the rate of reproductive aging. Combining mechanistic studies with
      evolutionary theory should allow us to define principles of the evolution of
      postembryonic development of ovaries, including the role of reproductive timing
      relative to sexual maturation. Achieving this will require identifying
      appropriate, and more experimentally tractable, taxa in which to study how early
      reproductive events influence lifetime fertility. We work with an invertebrate
      species, the cockroach Nauphoeta cinerea, with a complex reproductive biology in
      which females experience reproductive cycles, give live birth, and show age
      related decline in fertility. Thus, N. cinerea provides an opportunity to use an
      experimental approach to examine mechanisms by which females lose reproductive
      potential as they delay reproduction. Our results demonstrate that the loss of
      both oocytes ready for fertilization and future oocytes in females that delay
      mating is because of apoptosis. We suggest that loss of fertility because of
      delayed mating may originate in a nonadaptive response in control of apoptosis
      through mistiming of reproduction.

PMID- 15876193
TI  - vasa and nanos expression patterns in a sea anemone and the evolution of
      bilaterian germ cell specification mechanisms.
AB  - Most bilaterians specify primordial germ cells (PGCs) during early embryogenesis
      using either inherited cytoplasmic germ line determinants (preformation) or
      induction of germ cell fate through signaling pathways (epigenesis). However,
      data from nonbilaterian animals suggest that ancestral metazoans may have
      specified germ cells very differently from most extant bilaterians. Cnidarians
      and sponges have been reported to generate germ cells continuously throughout
      reproductive life, but previous studies on members of these basal phyla have not
      examined embryonic germ cell origin. To try to define the embryonic origin of
      PGCs in the sea anemone Nematostella vectensis, we examined the expression of
      members of the vasa and nanos gene families, which are critical genes in
      bilaterian germ cell specification and development. We found that vasa and nanos
      family genes are expressed not only in presumptive PGCs late in embryonic
      development, but also in multiple somatic cell types during early embryogenesis.
      These results suggest one way in which preformation in germ cell development
      might have evolved from the ancestral epigenetic mechanism that was probably used
      by a metazoan ancestor.

PMID- 15876196
TI  - Developmental instability of the Drosophila wing as an index of genomic
      perturbation and altered cell proliferation.
AB  - We experimentally induced different levels of instability affecting the
      development of specific wing regions of Drosophila melanogaster using the UAS
      GAL4 system. A common index of developmental instability is fluctuating asymmetry
      (FA), that is, random differences between body sides of single individuals. We
      studied the FA in transgenic strains carrying random genomic insertions (UAS
      strains), as well as insertions in the regulatory region of genes involved in the
      organization of wing development (GAL4 strains). In addition, the expression of
      genes that increase (dp110 and 3622) or decrease (dPTEN) cell proliferation was
      ectopically induced. Our results are related to different levels of perturbation.
      Through the first kind of perturbation, genome integrity was compromised by the
      insertion of foreign DNA. In all cases, we observed a general increase in FA,
      although it was rarely found significant. The second kind of perturbation
      involved a modification of genes controlling wing development through the
      insertion of a GAL4 sequence in their promoter region. The third kind involved
      the ectopic expression of genes controlling cell proliferation. Our results show
      that (i) the level of FA is connected with the level of morphological
      perturbation induced, (ii) FA increase was higher in the wing regions that were
      the target of the genetic perturbation, and (iii) developmental instability was
      also observed in regions that were not directly addressed by the perturbation.
      The results were discussed on the basis of the running models about Drosophila
      wing development.

PMID- 15876195
TI  - Expression of estrogen-receptor related receptors in amphioxus and zebrafish:
      implications for the evolution of posterior brain segmentation at the
      invertebrate-to-vertebrate transition.
AB  - Summary The evolutionary origin of vertebrate hindbrain segmentation is unclear
      since the amphioxus, the closest living invertebrate relative to the vertebrates,
      possesses a hindbrain homolog that displays no gross morphological segmentation.
      Three of the estrogen-receptor related (ERR) receptors are segmentally expressed
      in the zebrafish hindbrain, suggesting that their common ancestor was expressed
      in a similar, reiterated manner. We have also cloned and determined the
      developmental expression of the single homolog of the vertebrate ERR genes in the
      amphioxus (AmphiERR). This gene is also expressed in a segmented manner in a
      region considered homologous to the vertebrate hindbrain. In contrast to the
      expression of amphioxus islet (a LIM-homeobox gene that also labels motoneurons),
      AmphiERR expression persists longer in the hindbrain homolog and does not later
      extend to additional posterior cells. In addition, AmphiERR and one of its
      vertebrate homologs (ERRalpha) are expressed in the developing somitic
      musculature of amphioxus and zebrafish, respectively. Altogether, our results are
      consistent with fine structural evidence suggesting that the amphioxus hindbrain
      is segmented, and indicate that chordate ERR gene expression is a marker for both
      hindbrain and muscle segmentation. Furthermore, our data support an evolution
      model of chordate brain segmentation: originally, the program for anterior
      segmentation in the protochordate ancestors of the vertebrates resided in the
      developing axial mesoderm which imposed reiterated patterning on the adjacent
      neural tube; during early vertebrate evolution, this segmentation program was
      transferred to and controlled by the neural tube.

PMID- 15876197
TI  - Heterochrony and geometric morphometrics: a comparison of cranial growth in Pan
      paniscus versus Pan troglodytes.
AB  - Heterochrony, the classic framework in which to study ontogeny and phylogeny, in
      essence relies on a univariate concept of shape. Though principal component (PC)
      plots of multivariate shape data seem to resemble classical bivariate allometric
      plots, the language of heterochrony cannot be translated directly into general
      multivariate methodology. We simulate idealized multivariate ontogenetic
      trajectories and explore their appearance in PC plots of shape space and size
      shape space. Only if the trajectories of two related species lie along exactly
      the same path in shape space can the classic terminology of heterochrony apply
      and pure dissociation of size change against shape change be detected. Regional
      heterochrony--the variation of apparent heterochrony by region--implies a
      dissociation of local growth fields and cannot be identified in an overall PC
      analysis. We exemplify a geometric morphometric approach to these issues using
      adult and subadult crania of 48 Pan paniscus and 47 Pan troglodytes specimens. On
      each specimen, we digitized 47 landmarks and 144 semilandmarks on facial curves
      and the external neurocranial surface. We reject the hypothesis of global
      heterochrony in the cranium of Pan as well as regional heterochrony for the lower
      face, the upper face, and the neurocranium.

PMID- 15876198
TI  - Quantitative trait loci mapping of floral and leaf morphology traits in
      Arabidopsis thaliana: evidence for modular genetic architecture.
AB  - Summary Morphological variation within organisms is integrated and often modular
      in nature. That is to say, the size and shape of traits tend to vary in a
      coordinated and structured manner across sets of organs or parts of an organism.
      The genetic basis of this morphological integration is largely unknown. Here, we
      report on quantitative trait loci (QTL) analysis of leaf and floral organ size in
      Arabidopsis thaliana. We evaluate patterns of genetic correlations among traits
      and perform whole-genome scans using QTL mapping methods. We detected significant
      genetic variation for the size and shape of each floral and leaf trait in our
      study. Moreover, we found large positive genetic correlations among sets of
      either flower or leaf traits, but low and generally nonsignificant genetic
      correlations between flower and leaf traits. These results support the hypothesis
      of independent floral and vegetative modules. We consider co-localization of QTL
      for different traits as support for a pleiotropic basis of morphological
      integration and modularity. A total of eight QTL affecting flower and three QTL
      affecting leaf traits were identified. Most QTL affected either floral or leaf
      traits, providing a general explanation for high correlations within and low
      correlations between modules. Only two genomic locations affected both flower and
      leaf growth. These results are discussed in the context of the evolution of
      modules, pleiotropy, and the putative homologous relationship between leaves and
      flowers.

PMID- 15876199
TI  - Letter regarding: Fisk, D.J. (2004). Bacon, Boole, Popper. Risk Analysis, 24(5),
      1097-1098.

PMID- 15876200
TI  - Tolerable or acceptable: a comparison of risk regulation in the United kingdom
      and in the Netherlands.
AB  - In managing major accident hazards in industry risk, both the United Kingdom and
      the Netherlands use quantitative risk analysis and quantified risk criteria.
      These should be understood in the historical, legal, and political context in
      which they were drawn up. Even when criteria are numerically the same they do not
      necessarily mean the same thing. The legal and historical context differs widely
      between the two countries. Nevertheless, it is surprising that the final results
      in terms of land use and levels of risk are very similar.